PMID- 26130056 TI - Serial Evaluation of Abdominal Fluid and Serum Amino-terminal pro-C-type Natriuretic Peptide in Dogs with Septic Peritonitis. AB - BACKGROUND: Serum N-terminal pro-C-natriuretic peptide (NT-proCNP) has shown promise as a diagnostic biomarker for sepsis. Its sensitivity to detect dogs with septic peritonitis (SP) is reportedly low, perhaps attributable to the compartmentalization of NT-proCNP in the abdominal cavity. OBJECTIVES: To evaluate the use of an ELISA for the measurement of NT-proCNP in canine abdominal fluid and to describe the peri-operative pattern of abdominal fluid and serum NT proCNP concentrations in dogs with SP. ANIMALS: Five client-owned dogs with nonseptic abdominal effusion of varying etiologies and 12 client-owned dogs with SP undergoing abdominal surgery and placement of a closed-suction abdominal drain (CSAD). Six dogs were included upon hospital admission; 6 were included the day after surgery. METHODS: Prospective pilot study. A commercially available ELISA kit was analytically validated for use on canine abdominal fluid. The NT-proCNP concentrations were measured in the abdominal fluid of control dogs, and in serum and abdominal fluid of dogs with SP from admission for CSAD removal. RESULTS: In dogs with SP, admission abdominal fluid NT-proCNP concentrations were lower than the concurrent serum concentrations (P = 0.031), and lower than control canine abdominal fluid concentrations (P = 0.015). Postoperatively, abdominal fluid NT proCNP concentrations remained lower than serum concentrations (P < 0.050), except on day 4. CONCLUSIONS AND CLINICAL IMPORTANCE: The ELISA kit was able to measure NT-proCNP in canine abdominal fluid. In dogs with SP, low serum NT-proCNP concentrations cannot be explained by abdominal compartmentalization. PMID- 26130057 TI - Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory. AB - Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID- 26130058 TI - Dysregulation of sphingosine 1 phosphate receptor-1 (S1P1) signaling and regulatory lymphocyte-dependent immunosuppression in a model of post-fingolimod MS rebound. AB - Fingolimod affords protection from MS by sequestering lymphocytes in secondary lymphoid organs via down regulation of their sphingosine 1 phosphate receptor (S1P1). Unexpectedly, accumulating evidence indicates that patients who discontinue fingolimod treatment may be at risk of rehearsal of magnetic resonance (MR) and clinical disease activity, sometimes featuring dramatic rebound. We therefore developed in vivo and in vitro models of post-fingolimod MS rebound to unravel its cellular and molecular mechanisms. The impact of fingolimod withdrawal on T regulatory lymphocytes was also investigated by means of cytofluorimetric analysis and antigen-specific lymphocyte proliferation assays. We show that mice with relapsing-remitting experimental autoimmune encephalomyelitis (EAE) undergo extremely severe, chronic disease rebound upon discontinuation of fingolimod. Remarkably, rebound is preceded by a burst of S1P1 overexpression in lymph node-entrapped lymphocytes that correlates with subsequent massive lymphocyte egress and widespread CNS immune infiltration. Also, consistent with the ability of S1P1 to counteract polarization and function of T regulatory lymphocytes their number and suppression of effector T cells is reduced by fingolimod suspension. Data disclose the first pathogenic mechanisms of post-fingolimod rebound that may be targeted for therapeutic intervention. PMID- 26130059 TI - Linking surface chemistry to optical properties of semiconductor nanocrystals. AB - The intricate chemistry occurring at the surface of semiconductor nanocrystals is crucial to tailoring their optical properties to a myriad of applications. This perspective aims to re-evaluate long held ideas in semiconductor nanocrystal surface science in the light of a body of new and rich research. We start by reviewing recent developments in ligand chemistry, followed by a discussion of spectroscopic and computational approaches used for advancing the poorly understood electronic structure of the surface. With the insights gained, we show how the surface impacts emissive behaviour and we summarize strategies to increase fluorescent quantum yield. This discussion is followed by a review of experimental approaches for quantitative analysis of the surface chemistry at concentrations relevant to spectroscopic measurements. We end by highlighting some new directions in ligand chemistry, namely all-inorganically passivated semiconductor nanocrystals and new applications of surface emission. PMID- 26130060 TI - Sedentary time is associated with the metabolic syndrome in older adults with mobility limitations--The LIFE Study. AB - BACKGROUND: Epidemiological and objective studies report an association between sedentary time and lower risk of the metabolic syndrome (MetS) and its risk factors in young and middle-age adults. To date, there is a lack of objective data on the association between sedentary time and MetS among older adults. METHODS: The association between objectively measured sedentary time (accelerometry) with MetS and MetS components was examined in a large sample of older adults with mobility limitations (N=1198; mean age=78.7 +/- 5.3 years) enrolled in the Lifestyle Interventions and Independence for Elders (LIFE) study. Participants were divided into tertiles according to percentage of daily sedentary time, and the relation between sedentary time with MetS and MetS components was examined after adjusting for age, sex, ethnicity, and BMI. RESULTS: Participants in the highest sedentary time tertile had significantly higher odds of MetS (OR=1.54) (95% CI 1.13 to 2.11) in comparison with participants in the lowest tertile (p=0.03). Participants in the highest sedentary time tertile had larger waist circumference (p=0.0001) and lower HDL-C (p=0.0003) than participants in the lowest sedentary time tertile. CONCLUSIONS: Sedentary time was strongly related to higher odds of MetS. These results, based on objectively measured sedentary time, suggest that sedentary time may represent an important risk factor for the development of MetS in older adults with high likelihood for disability. PMID- 26130061 TI - Aldehyde dehydrogenase 2 genetic variations may increase susceptibility to Parkinson's disease in Han Chinese population. AB - Genetic variations of ALDH2, encoding aldehyde dehydrogenase-2 which regulates aldehyde oxidation in the brain, have been recently suggested to impact on the association of pesticide exposure with Parkinson's disease (PD). However, the link between ALDH2 polymorphism and PD remains elusive. In the present study, tag single nucleotide polymorphisms of ALDH2, including rs4767944, rs441, and rs671, were extracted and analyzed in a Chinese cohort consisting of 584 PD patients and 582 controls. Results from genotyping analyses showed that rs4767944 (p = 0.002), but not rs441 and rs671, were associated with PD. The C allele of rs4767944 served a risk factor toward PD. Further analysis presented a significant association between haplotype frequencies and the risk for PD, primarily driven by the preponderance of the C-T-A (p = 0.03) or C-T-G (p = 0.003) haplotype of rs4767944, rs441, and rs671 in PD patients. In conclusion, these novel results suggest an association between PD susceptibility and ALDH2 genetic variations. PMID- 26130062 TI - Perimenopausal hormone therapy is associated with regional sparing of the CA1 subfield: a HUNT MRI study. AB - Observational studies support a neuroprotective role of hormone therapy (HT) in the perimenopause, with hippocampal size being a widely used biomarker. We investigated the effect of HT started before the onset of menopause and lasting for at least 3 years on hippocampal volume and shape in 80 postmenopausal women and 80 controls matched on age and intracranial volume taken from a large community-based sample (Nord-Trondelag Health Study-magnetic resonance imaging). The main effect of hormone group showed a statistically significant difference in hippocampal volumes (p = 0.028). Both the right (3.2%) and left (2.8%) hippocampal volumes were larger in the HT group but only significant for the right hippocampus (p = 0.023). Shape analysis revealed significant regional sparing of the medial aspect of the right hippocampal head and lateral aspect of the body extending to the tail, corresponding to the cornu ammonis, including part of the subiculum, in the HT group. A similar nonsignificant pattern was observed in the left hippocampus. The present study provides support for the critical window theory demonstrating that HT initiated in the perimenopause has neuroprotective properties. PMID- 26130063 TI - Investigating the role of Sirt1-modulated oxidative stress in relation to benign paroxysmal positional vertigo and Parkinson's disease. AB - Benign paroxysmal positional vertigo (BPPV) is one of the most frequently encountered primary complaints in dizziness clinics. The incidence of BPPV has been proven to increase with age. The relationship between BPPV and another neurodegenerative disease, Parkinson's disease (PD), has not been previously discussed. This study aimed to investigate the relationship of BPPV and PD with oxidative stress. A total of 30,811 subjects participated in our cohort study. The study cohort comprised 5057 BPPV patients and a comparison cohort of 25,754 nonBPPV patients. SIRT1 axis gene expression was investigated in BPPV patient blood samples and a PD cell model of 6-hydroxydopamine (6-OHDA)-treated PC-12 cells to elucidate the potential in vitro and in vivo mechanisms of degeneration in PD and BPPV. Our data suggest that BPPV patients with histories of head injuries show a significantly higher hazard to develop subsequent PD (hazard ratio, 3.942; confidence interval, 1.523-10.205, p = 0.005). We also observed that oxidative status is increased in blood samples from patients with BPPV. Our in vitro study suggests that SIRT1 function is inhibited by oxidative stress, which thereby promotes 6-hydroxydopamine-induced cell death. We conclude that BPPV is independently associated with an increased risk of PD. This finding may be attributed to oxidative stress-mediated inhibition of SIRT1 expression levels. PMID- 26130064 TI - IL10R2 Overexpression Promotes IL22/STAT3 Signaling in Colorectal Carcinogenesis. AB - The mucosal immune response in the setting of intestinal inflammation contributes to colorectal cancer. IL10 signaling has a central role in gut homeostasis and is impaired in inflammatory bowel disease (IBD). Out of two IL10 receptor subunits, IL10R1 and IL10R2, the latter is shared among the IL10 family of cytokines and activates STAT signaling. STAT3 is oncogenic in colorectal cancer; however, knowledge about IL10 signaling upstream of STAT3 in colorectal cancer is lacking. Here, expression of IL10 signaling genes was examined in matched pairs from normal and tumor tissue from colorectal cancer patients showing overexpression (mRNA, protein) of IL10R2 and STAT3 but not IL10R1. IL10R2 overexpression was related to microsatellite stability. Transient overexpression of IL10R2 in HT29 cells increased proliferation upon ligand activation (IL10 and IL22). IL22, and not IL10, phosphorylated STAT3 along with increased phosphorylation of AKT and ERK. A significantly higher expression of IL22R1 and IL10R2 was also confirmed in a separate cohort of colorectal cancer samples. IL22 expression was elevated in gut mucosa from patients with IBD and colitis-associated cancer, which also exhibited increased expression of IL22R1 but not its coreceptor IL10R2. Overall, these data indicate that overexpression of IL10R2 and STAT3 contributes to colorectal carcinogenesis in microsatellite-stable tumors through IL22/STAT3 signaling. PMID- 26130065 TI - Phase I Trial of a Yeast-Based Therapeutic Cancer Vaccine (GI-6301) Targeting the Transcription Factor Brachyury. AB - The nuclear transcription factor brachyury has previously been shown to be a strong mediator of the epithelial-to-mesenchymal transition (EMT) in human carcinoma cells and a strong negative prognostic factor in several tumor types. Brachyury is overexpressed in a range of human carcinomas as well as in chordoma, a rare tumor for which there is no standard systemic therapy. Preclinical studies have shown that a recombinant Saccharomyces cerevisiae (yeast) vaccine encoding brachyury (GI-6301) can activate human T cells in vitro. A phase I dose escalation (3+3 design) trial enrolled 34 patients at 4 dose levels [3, 3, 16, and 11 patients, respectively, at 4, 16, 40, and 80 yeast units (YU)]. Expansion cohorts were enrolled at 40- and 80-YU dose levels for analysis of immune response and clinical activity. We observed brachyury-specific T-cell immune responses in the majority of evaluable patients despite most having been heavily pretreated. No evidence of autoimmunity or other serious adverse events was observed. Two chordoma patients showed evidence of disease control (one mixed response and one partial response). A patient with colorectal carcinoma, who enrolled on study with a large progressing pelvic mass and rising carcinoembryonic antigen (CEA), remains on study for greater than 1 year with stable disease, evidence of decreased tumor density, and decreased serum CEA. This is the first-in-human study to demonstrate the safety and immunogenicity of this therapeutic cancer vaccine and provides the rationale for exploration in phase II studies. A randomized phase II chordoma study is now enrolling patients. PMID- 26130066 TI - Agents Which Inhibit NF-kappaB Signaling Block Spontaneous Contractile Activity and Negatively Influence Survival of Developing Myotubes. AB - Inhibiting the NF-kappaB signaling pathway provides morphological and functional benefits for the mdx mouse, a model for Duchenne muscular dystrophy characterized by chronic elevations in the nuclear expression of p65, the transactivating component of the NF-kappaB complex. The purpose of this study was to examine p65 expression in nondystrophic and mdx myotubes using confocal immunofluorescence, and determine whether inhibitors of the NF-kappaB pathway alter myotube development. Primary cultures of nondystrophic and mdx myotubes had identical levels of nuclear and cytosolic p65 expression and exhibited equivalent responses to TNF-alpha, thus excluding the hypothesis that the lack of dystrophin is sufficient to induce increases in NF-kappaB signaling. The NF-kappaB inhibitors pyrrolidine dithiocarbamate (PDTC) and sulfasalazine decreased spontaneous contractile activity and reduced myotube viability in a dose- and time-dependent manner. Similarly, a vivo-morpholino designed to block translation of murine p65 (m-p65tb-vivomorph1) rapidly abolished spontaneous contractile activity, reduced p65 expression measured by confocal immunofluorescence, and induced cell death in primary cultures of nondystrophic and mdx myotubes. Similar effects on p65 immunofluorescence and cell viability were observed following m-p65tb-vivomorph1 exposure to spontaneously inactive C2C12 myotubes, while exposure to a control scrambled vivo morpholino had no effect. These results indicate a direct role of the NF-kappaB pathway in myotube development and identify a potential therapeutic limitation to the use of NF-kappaB inhibitors in treating Duchenne and related muscular dystrophies. J. Cell. Physiol. 231: 788-797, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26130067 TI - Synergistic effects of betel quid chewing, tobacco use (in the form of cigarette smoking), and alcohol consumption on the risk of malignant transformation of oral submucous fibrosis (OSF): a case-control study in Hunan Province, China. AB - OBJECTIVES: Oral submucous fibrosis (OSF) is a potentially malignant disorder, wherein 7% to 13% of patients with OSF develop oral squamous cell carcinoma (OSCC) at clinically coincident sites established to have OSF. We aimed at investigating the lifestyle-related risk factors for malignant transformation of OSF. STUDY DESIGN: A case-control study was conducted among 80 cases with OSF associated OSCC and 80 controls with OSF but without clinically or histopathologically evident OSCC, recruited from January 2012 to October 2014 in the Xiangya Hospital, Hunan Province, Mainland China. RESULTS: The odds ratios (OR) for OSCC were 13.3 (95% confidence interval [95% CI]: 3.1-56.4) and 45.1 (95% CI: 9.6-212.9) at the highest exposure of betel quid (BQ) chewing, by duration and frequency, respectively. Higher risks were also found to be associated with the consumption of cigarette (OR = 5.0, 95% CI: 1.7-14.8) and alcohol (OR = 3.1, 95% CI: 1.1-8.6). Adjusted ORs increased substantially among patients who consumed BQ and cigarette or alcohol simultaneously, which were 26.1 (95% CI: 4.0-172.6) and 55.-(95% CI: 1.8-1742.8) at the longest duration, and 160.3 (95% CI: 18.7-11371.2) and 58.1 (95% CI: 2.4-1434.9) at the highest dose, respectively. CONCLUSIONS: The use of BQ, cigarette, and alcohol were identified as risk factors for malignant transformation of OSF in the Hunan province, Mainland China. Synergistic effects between BQ chewing and cigarette or alcohol consumption were revealed. PMID- 26130068 TI - Magnetic resonance tomography of the knee joint. AB - OBJECTIVES: To compare the diagnostic performance of magnetic resonance imaging (MRI) in terms of sensitivity and specificity using a field strength of <1.0 T (T) versus >=1.5 T for diagnosing or ruling out knee injuries or knee pathologies. METHODS: The systematic literature research revealed more than 10,000 references, of which 1598 abstracts were reviewed and 87 full-text articles were retrieved. The further selection process resulted in the inclusion of four systematic reviews and six primary studies. RESULTS: No differences could be identified in the diagnostic performance of low- versus high-field MRI for the detection or exclusion of meniscal or cruciate ligament tears. Regarding the detection or grading of cartilage defects and osteoarthritis of the knee, the existing evidence suggests that high-field MRI is tolerably specific but not very sensitive, while there is literally no evidence for low-field MRI because only a few studies with small sample sizes and equivocal findings have been performed. CONCLUSIONS: We can recommend the use of low-field strength MRI systems in suspected meniscal or cruciate ligament injuries. This does, however, not apply to the diagnosis and grading of knee cartilage defects and osteoarthritis because of insufficient evidence. PMID- 26130069 TI - Inter-observer agreement of CT measurement of the glenoid bone surface by the CT Pico method: Comparison with laser in a cadaveric model. AB - OBJECTIVE: The aim of this study was to test reproducibility of the CT Pico method in a cadaveric model and to compare CT Pico measurements with a high precision laser probe for optical scanning. MATERIALS AND METHODS: The glenoid surface of ten dried cadaveric scapulae (with intact surface) was measured by and high-precision laser probe for optical scanning, the latter being assumed as a reference standard. Measurements were done according to the Pico technique, using a circle-shaped region of interest (ROI) that was placed on the inferior glenoid rim. Measurements obtained using the CT Pico method (three readers) and with laser were compared to assess differences between radiological assessment and the reference standard. Each observer performed two repeated measurements from each scapulae (20 for each observer). RESULTS: Mean differences between laser measurements and each CT reader were 18.4% (range, -4 to 61%) for reader 1, 12.4% (range, -15 to 64%) for reader 2, and 11% (range, -14 to 58%) for reader 3. Considering all the 60 measurements made by the three readers, 39 measurements out of 60 (65%) were outside the range [-5%; +5%] while 26 measurements (43%) are outside the range [-10%; +10%]. The largest differences (positive and negative) were +64 and -14 %, respectively. Intra-operator reproducibility was high in most cases (intraclass correlation coefficient (ICC) =0.93, ICC = 0.91, ICC = 0.93 and Lin's Concordance correlation coefficient (CCC) = 0.92, CCC = 0.90, CCC = 0.92 for reader 1 to 3, respectively. However, in five cases the CT Pico measurements showed absolute differences between the first and second measurements that exceeded 10%. CONCLUSIONS: The inter-observer variability for CT measurement of the glenoid surface using the CT Pico method was high when compared with laser, in the assessment of glenoid surface in cadaveric specimens, thus the CT Pico method is not reliable and could cause errors in the clinical management of the patient. Level of evidence Level II, Development of diagnostic criteria on consecutive patients (with universally applied reference "gold" standard). PMID- 26130070 TI - Effect of zoledronic acid on vertebral marrow adiposity in postmenopausal osteoporosis assessed by MR spectroscopy. AB - OBJECTIVE: Zoledronic acid (ZOL) has a suppressive effect on marrow adiposity in ovariectomized rats. Currently, however, data on the effect of ZOL on marrow fat in humans are unavailable. The purpose of this work was to determine the in vivo effect of ZOL on bone remodeling and marrow adipogenesis in postmenopausal osteoporosis. MATERIALS AND METHODS: In a 12-month, randomized, double-blind, placebo-controlled trial, we studied 100 postmenopausal women with osteoporosis who were randomly given either a single dose of intravenous infusion of ZOL (5 mg) or placebo. All subjects received adequate dietary calcium and vitamin D3. Main outcome measures included bone mineral density by dual-energy X-ray absorptiometry, vertebral marrow fat content by proton MR spectroscopy, serum markers of bone turnover by biochemical analysis. RESULTS: Ninety percent of the participants completed the 12-month follow-up. With respect to baselines, marrow fat content reduced by 8.1% in the ZOL-treated women and increased by 3.0% in the controls (all p < 0.05). In addition, there were significant increases of bone mineral density by 2.8, 2.0, and 1.7% in the lumbar spine, femoral neck, and total hip, respectively, in the ZOL group compared with the placebo group. Serum levels of bone resorption marker CTX and bone formation marker BALP decreased by 33 and 18% in postmenopausal women receiving ZOL. CONCLUSIONS: In postmenopausal women with osteoporosis, a single dose of ZOL therapy significantly reduced marrow adiposity. MR spectroscopy of vertebral marrow fat may therefore serve as a novel tool for BMD-independent efficacy assessment. PMID- 26130071 TI - Extradigital glomus tumor in the knee: excision with ultrasound guided needle localization. AB - Glomus tumors are rare neoplasms that are usually subungual in location, but can infrequently be found elsewhere in the body. When they occur in extradigital locations, they present a diagnostic challenge that may result in delay of definitive management. We report a case of a 51-year-old male who experienced decade long chronic pain because of a glomus tumor in the suprapatellar fat pad of the knee. This case is unique not only because of the glomus tumor's location, but also because it ultimately required ultrasound-guided needle localization for excision. PMID- 26130072 TI - The effect of long term under- and over-feeding on the expression of six major milk protein genes in the mammary tissue of sheep. AB - Milk protein synthesis in the mammary gland involves expression of six major milk protein genes whose nutritional regulation remains poorly defined. In this study, the effect of long term under- and over-feeding on the expression of alphas1 casein: CSN1S1, alphas2-casein: CSN1S2, beta-casein: CSN2, kappa-casein: CSN3, alpha-lactalbumin: LALBA and beta-lactoglobulin: BLG gene in sheep mammary tissue (MT) was examined. Twenty-four lactating dairy sheep, at 90-98 d in milk, were divided into three groups and fed the same ration, for 60 d, in quantities which met 70% (underfeeding), 100% (control) and 130% (overfeeding) of their energy and crude protein requirements. The results showed a significant reduction on mRNA of CSN1S1, CSN1S2, CSN2 and BLG gene in the MT of underfed sheep compared with the overfed ones and a significant reduction in CSN3 and LALBA gene expression compared with the respective control animals. Significant positive correlations were observed between the mRNA levels of milk proteins' genes with the milk protein yield and milk yield respectively. In conclusion, the feeding level and consequently the nutrients availability, affected the milk protein yield and milk volume by altering the CSN1S1, CSN1S2, CSN2, CSN3, LALBA and BLG gene expression involved in their metabolic pathways. PMID- 26130073 TI - Targeted knockout of TNF-alpha by injection of lentivirus-mediated siRNA into the subacromial bursa for the treatment of subacromial bursitis in rats. AB - Subacromial bursitis (SAB) is the major source of pain in rotator cuff disease. Although multiple investigations have provided support for the role of inflammatory cytokines in SAB, few have focussed on the use these cytokines in the treatment of SAB. The aim of the present study was to observe the therapeutic efficacy of lentivirus-mediated RNA interference (RNAi) on carrageenan-induced SAB by injecting lentivirus-tumor necrosis factor (TNF)-alpha-RNAi expressing TNF alpha small interfering (si)RNA. Using screened siRNA segments, an siRNA was designed. A lentivirus vector expressing siRNA was established and packed as lentivirus particles. A lentivirus that expressed the negative sequence was used as a lentivirus-negative control (NC). The carrageenan-induced SAB model was established in 32 male Sprague-Dawley rats. The modeled rats were randomly assigned to four groups: Lentivirus-RNAi treatment group, lentivirus-NC group, SAB group and phosphate-buffered saline (PBS) blank control group. The lentivirus was injected (1x10(7) transducing units) into the subacromial bursa of the rats in the lentivirus-RNAi group and lentivirus-NC group, whereas 100 ul PBS was injected at the same site in the SAB group and the PBS blank control group. At 5 weeks following injection, the animals were sacrificed and venous blood was obtained. The effect of TNF-alpha interference and the expression of inflammatory cytokines were determined by reverse transcription-quantitative polymerase chain reaction, western blotting, hematoxylin and eosin staining, Van Gieson's staining and immunofluorescence. The expression of TNF-alpha was decreased in the lentivirus-TNF-alpha-RNAi group compared with that in the SAB group. Morphological observations revealed that the number of inflammatory cells were reduced and damage to tendon fibers was attenuated in this group, suggesting that the downregulation of the protein expression levels of TNF-alpha-associated nuclear factor-kappaB, matrix metalloproteinase (MMP)1, MMP9, cyclooxygenase (COX)-1 and COX-2 may exert a therapeutic effect on inflammation of the SAB caused by rheumatoid arthritis. It was also found that the expression of stromal cell-derived growth factor-1 was downregulated in the lentivirus-TNF-alpha-RNAi group. Therefore, the present study demonstrated that lentivirus-mediated TNF alpha RNAi effectively inhibited the inflammatory response in SAB, and that injection of a lentivirus vector into the affected region is an effective way of achieving RNAi in vivo. PMID- 26130074 TI - MENTAL HEALTH DISORDERS SUBSEQUENT TO GESTATIONAL DIABETES MELLITUS DIFFER BY RACE/ETHNICITY. AB - INTRODUCTION: The relationship between gestational diabetes mellitus (GDM) and postpregnancy mental health disorders has been inconsistently reported. Additionally, race/ethnicity data are limited. We sought to elucidate the intersection of these relationships. METHODS: We analyzed 18,109 women aged 18-40 with self-reported race/ethnicity. Women with (n = 659) and without (n = 14,461) GDM were followed for a median of 4.4 (interquartile range 1.4-6.8) and 4.0 (1.5 6.4) years, respectively, for incident mental health disorders. Multivariable repeated measures analyses were conducted to examine associations between GDM and postpregnancy mental health disorders, race/ethnicity, and the interaction of these factors. RESULTS: Women with compared to women without GDM were older (mean +/- standard deviation, 32 +/- 5 vs. 30 +/- 5 years; P < .001) and had higher body mass index (29.0 +/- 7.2 vs. 25.3 +/- 5.2 kg/m(2) ; P < .001). GDM was associated with increased risk for depression and anxiety after adjusting for age and pregnancy complications; however, loss of significance in the fully adjusted model for depression (odds ratio [95% CI]: 1.29 [0.98, 1.70]; P = .064) and anxiety (1.14 [0.83, 1.57], P = .421) suggested that clinical and socioeconomic factors influence this relationship. Hispanic compared to white women had a greater risk for depression (1.40 [1.15, 1.72]; P = .001), even after multivariable adjustment. The interaction between GDM and race was evident in complication-adjusted but not fully adjusted models. CONCLUSIONS: The incidence of mental health disorders subsequent to GDM was attenuated after adjustment for clinical and socioeconomic factors. Moreover, race/ethnicity influenced this relationship. Further investigation is warranted to clarify potential underlying mechanisms. PMID- 26130075 TI - PRomotion Of Physical activity through structured Education with differing Levels of ongoing Support for people at high risk of type 2 diabetes (PROPELS): study protocol for a randomized controlled trial. AB - BACKGROUND: The prevention of type 2 diabetes is recognised as a health care priority. Lifestyle change has proven effective at reducing the risk of type 2 diabetes, but limitations in the current evidence have been identified in: the promotion of physical activity; availability of interventions that are suitable for commissioning and implementation; availability of evidence-based interventions using new technologies; and physical activity promotion among ethnic minorities. We aim to investigate whether a structured education programme with differing levels of ongoing support, including text-messaging, can increase physical activity over a 4 year period in a multi-ethnic population at high risk of diabetes. METHODS/DESIGN: A multi-centre randomised controlled trial, with follow-up at 12 and 48 months. The primary outcome is change in ambulatory activity at 48 months. Secondary outcomes include changes to markers of metabolic, cardiovascular, anthropometric and psychological health along with cost-effectiveness. Participants aged 40-74 years for White European, or 25-74 years for South Asians, with an HbA1c value of between 6.0 and < 6.4% (42 and 47 mmol/mol) or with a previously recorded plasma glucose level or HbA1c value within the high risk (prediabetes) range within the last five years, are invited to take part in the trial. Participants are identified through primary care, using an automated diabetes risk score within their practice database, or from a database of previous research participants. Participants are randomly assigned to either: 1) the control group who receive a detailed advice leaflet; 2) the Walking Away group, who receive the same leaflet and attend a 3 hour structured education programme with annual maintenance sessions delivered in groups; or 3) the Walking Away Plus group, who receive the leaflet, attend the structured education programme with annual maintenance sessions, plus receive follow-on support through highly-tailored text-messaging and telephone calls to help to aid pedometer use and behaviour change. DISCUSSION: This study will provide new evidence for the long-term effectiveness of a structured education programme focused on physical activity, conducted within routine care in a multi-ethnic population in the UK. It will also investigate the impact of different levels of ongoing support and the cost-effectiveness of each intervention. TRIAL REGISTRATION: ISRCTN83465245 Trial registration date: 14/06/2012. PMID- 26130077 TI - Right ventricular function after aortic valve replacement: a pilot study comparing surgical and transcatheter procedures using 3D echocardiography. AB - OBJECTIVES: Previous studies have found that standard echocardiographic measures of right ventricular (RV) function were impaired after surgical replacement of the aortic valve (SAVR), but not after transcatheter aortic valve implantation (TAVI). We used 3D echocardiography to gain further insight into the changes of RV performance in patient undergoing SAVR or TAVI. METHODS: We conducted a prospective non-randomized study with two parallel groups and performed echocardiographic evaluation in 20 patients with aortic stenosis undergoing SAVR (age 77 +/- 4 years), and in 20 patients undergoing TAVI via the transfemoral approach (age 83 +/- 6 years) 1 week before and between the fifth and seventh day after the procedure. RESULTS: Tricuspid annular plane systolic excursion was postoperatively markedly reduced in patients undergoing SAVR (13 +/- 2 vs 26 +/- 4 mm, post- vs preoperative, P < 0.001), but not in patients undergoing TAVI (24 +/- 7 vs 24 +/- 5 mm, P = 0.90). Fractional shortening of the RV midcavity transverse diameter, however, increased after SAVR (50 +/- 8 vs 31 +/- 11%, P < 0.001) in contrast to TAVI (33 +/- 10 vs 34 +/- 9%, P = 0.85). The RV ejection fraction, assessed by 3D echocardiography, remained unchanged in both patient groups (SAVR, 55 +/- 6 vs 55 +/- 7%, P = 0.52; TAVI, 56 +/- 8 vs 54 +/- 7%, P = 0.28). CONCLUSIONS: RV longitudinal contraction decreased after SAVR, whereas RV transverse contraction increased. Both parameters did not change after TAVI. RV ejection fraction and RV stroke volume remained constant irrespective of the technique of aortic valve replacement, thus indicating that global systolic RV function is not compromised after SAVR. PMID- 26130076 TI - Biomarker discovery: quantification of microRNAs and other small non-coding RNAs using next generation sequencing. AB - BACKGROUND: Small ncRNAs (sncRNAs) offer great hope as biomarkers of disease and response to treatment. This has been highlighted in the context of several medical conditions such as cancer, liver disease, cardiovascular disease, and central nervous system disorders, among many others. Here we assessed several steps involved in the development of an ncRNA biomarker discovery pipeline, ranging from sample preparation to bioinformatic processing of small RNA sequencing data. METHODS: A total of 45 biological samples were included in the present study. All libraries were prepared using the Illumina TruSeq Small RNA protocol and sequenced using the HiSeq2500 or MiSeq Illumina sequencers. Small RNA sequencing data was validated using qRT-PCR. At each stage, we evaluated the pros and cons of different techniques that may be suitable for different experimental designs. Evaluation methods included quality of data output in relation to hands-on laboratory time, cost, and efficiency of processing. RESULTS: Our results show that good quality sequencing libraries can be prepared from small amounts of total RNA and that varying degradation levels in the samples do not have a significant effect on the overall quantification of sncRNAs via NGS. In addition, we describe the strengths and limitations of three commercially available library preparation methods: (1) Novex TBE PAGE gel; (2) Pippin Prep automated gel system; and (3) AMPure XP beads. We describe our bioinformatics pipeline, provide recommendations for sequencing coverage, and describe in detail the expression and distribution of all sncRNAs in four human tissues: whole-blood, brain, heart and liver. CONCLUSIONS: Ultimately this study provides tools and outcome metrics that will aid researchers and clinicians in choosing an appropriate and effective high-throughput sequencing quantification method for various study designs, and overall generating valuable information that can contribute to our understanding of small ncRNAs as potential biomarkers and mediators of biological functions and disease. PMID- 26130078 TI - Education and Executive Function Mediate Engagement in Advance Care Planning in Early Cognitive Impairment. AB - BACKGROUND: Advance care planning (ACP) is an important component to holistic care for people with early cognitive impairment (ECI) who are generally still mentally capable of making rational decisions. This study explores the willingness of people with ECI to engage in ACP and how clinical and behavioral variables shape their decisions. METHODS: Ninety-eight persons with ECI (mild cognitive impairment or early dementia, Clinical Dementia Rating = 0.5/1.0) and assessed to have adequate insight (Clinical Insight Rating Scale) underwent an ACP information session. They were assessed on their knowledge of dementia (Knowledge of Alzheimer Disease) and willingness to engage in ACP, and were interviewed on their beliefs and attitudes toward ACP (Perceived Barriers and Benefits Scale to ACP). Univariate analysis and logistic regression identified factors that predicted persons willing or unwilling to engage in ACP based on their responses to the perceived barriers and benefits of ACP as well as sociodemographic and clinical variables. RESULTS: Fifty-two persons (54%) were keen on ACP. On univariate analysis, persons with better executive function [Frontal Assessment Battery (FAB)] (t = -3.63, P < .0001), were more educated (t = -2.11, P = .038) and had lower barriers to ACP (t = 2.47, P = .015), particularly less "passive coping" (t = 2.83, P = .006), were more keen on ACP. Logistic regression revealed that the combined predictive model comprising FAB, education, and passive coping as a whole reliably differentiated those unwilling to engage in ACP from those who were willing (chi(2) = 18.995, P = .001 with df = 4). Wald criterion showed that FAB (P = .016) and passive coping (P = .023) contributed most to prediction. CONCLUSIONS: Better education and executive function predict willingness to engage in ACP, and these factors are instrumental in a person's ability to acquire knowledge and process information. Initiating ACP discussions early, increasing efforts at education, and providing tailored information are important interventions that facilitate completion of ACP. PMID- 26130079 TI - Testing Penetration of Epoxy Resin and Diamine Hardeners through Protective Glove and Clothing Materials. AB - Efficient, comfortable, yet affordable personal protective equipment (PPE) is needed to decrease the high incidence of allergic contact dermatitis arising from epoxy resin systems (ERSs) in industrial countries. The aim of this study was to find affordable, user-friendly glove and clothing materials that provide adequate skin protection against splashes and during the short contact with ERS that often occurs before full cure. We studied the penetration of epoxy resin and diamine hardeners through 12 glove or clothing materials using a newly developed test method. The tests were carried out with two ERS test mixtures that had a high content of epoxy resin and frequently used diamine hardeners of different molar masses. A drop (50 ul) of test mixture was placed on the outer surface of the glove/clothing material, which had a piece of Fixomull tape or Harmony protection sheet attached to the inner surface as the collection medium. The test times were 10 and 30 min. The collecting material was removed after the test was finished and immersed into acetone. The amounts of diglycidyl ether of bisphenol A (DGEBA), isophorone diamine (IPDA), and m-xylylenediamine (XDA) in the acetone solution were determined by gas chromatography with mass spectrometric detection. The limit for acceptable penetration of XDA, IPDA, and DGEBA through glove materials was set at 2 ug cm(-2). Penetration through the glove materials was 1.4 ug cm(-2) or less. The three tested chemical protective gloves showed no detectable penetration (<0.5 ug cm(-2)). Several affordable glove and clothing materials were found to provide adequate protection during short contact with ERS, in the form of, for example, disposable gloves or clothing materials suitable for aprons and as additional protective layers on the most exposed parts of clothing, such as the front of the legs and thighs and under the forearms. Every ERS combination in use should be tested separately to find the best skin protection material, and this can be done by using this simple test method. PMID- 26130080 TI - Cystic illusion: superior mesenteric vein aneurysm thrombosis mimicking a pancreatic cyst. PMID- 26130081 TI - FastME 2.0: A Comprehensive, Accurate, and Fast Distance-Based Phylogeny Inference Program. AB - FastME provides distance algorithms to infer phylogenies. FastME is based on balanced minimum evolution, which is the very principle of Neighbor Joining (NJ). FastME improves over NJ by performing topological moves using fast, sophisticated algorithms. The first version of FastME only included Nearest Neighbor Interchange. The new 2.0 version also includes Subtree Pruning and Regrafting, while remaining as fast as NJ and providing a number of facilities: Distance estimation for DNA and proteins with various models and options, bootstrapping, and parallel computations. FastME is available using several interfaces: Command line (to be integrated in pipelines), PHYLIP-like, and a Web server (http://www.atgc-montpellier.fr/fastme/). PMID- 26130083 TI - Bi5 O7 I Nanobelts: Synthesis, Modification, and Photocatalytic Antifouling Activity. AB - Bi5 O7 I nanobelts were prepared by a facile hydrothermal method to study the crystal phase transformation and morphology evolution. Based on these results, a crystal growth mechanism of Bi5 O7 I nanobelts was proposed. To enhance the photocatalytic antifouling activity, ethanol or TiCl3 was used to modify the Bi5 O7 I nanobelts. The resulting BiOI/Bi2 O2 CO3 /Bi5 O7 I and TiO2 /BiOCl/Bi5 O7 I micro-nanostructures show excellent degradation activity of malachite green and bactericidal effects against Pseudomonas aeruginosa, which may be attributed to the higher charge carrier separation efficiency of these heterojunction structures. The results indicate that the formation of semiconductor composites is a very effective strategy to design high-performance photocatalyst systems. PMID- 26130082 TI - Multiple Resistance at No Cost: Rifampicin and Streptomycin a Dangerous Liaison in the Spread of Antibiotic Resistance. AB - Evidence is mounting that epistasis is widespread among mutations. The cost of carrying two deleterious mutations, or the advantage of acquiring two beneficial alleles, is typically lower that the sum of their individual effects. Much less is known on epistasis between beneficial and deleterious mutations, even though this is key to the amount of genetic hitchhiking that may occur during evolution. This is particularly important in the context of antibiotic resistance: Most resistances are deleterious, but some can be beneficial and remarkably rifampicin resistance can emerge de novo in populations evolving without antibiotics. Here we show pervasive positive pairwise epistasis on Escherichia coli fitness between beneficial mutations, which confer resistance to rifampicin, and deleterious mutations, which confer resistance to streptomycin. We find that 65% of double resistant strains outcompete sensitive bacteria in an environment devoid of antibiotics. Weak beneficial mutations may therefore overcome strong deleterious mutations and can even render double mutants strong competitors. PMID- 26130084 TI - Delayed esophageal perforation after anterior cervical fusion and retropharyngeal steroid use: a report of two cases. AB - BACKGROUND CONTEXT: Prevertebral soft-tissue swelling (PSTS) after anterior cervical spine surgery may result in postoperative catastrophic airway complications and persistent dysphagia. Systemic or local corticosteroids have been used to decrease complications related to PSTS. To date, studies using retropharyngeal steroid (RS) have not reported complications with local steroids such as infection, pseudarthrosis, and other systemic adverse effects. PURPOSE: The aim was to report delayed esophageal perforation in two patients who underwent anterior cervical spine surgery and RS use. STUDY DESIGN/SETTING: This was a case report with a review of literature. METHODS: We presented two cases of delayed esophageal perforation without obvious cause in two patients who underwent anterior cervical spine surgery and RS use. RESULTS: A 45-year-old woman underwent C5-C6 anterior cervical discectomy and fusion (ACDF) for radiculopathy. Just before closing the wound, one ampule of triamcinolone acetate was placed in the retropharyngeal space. Two months postoperatively, she presented to the emergency department with clinical symptoms of esophageal perforation. Radiographic studies demonstrated a retropharyngeal abscess. A 0.5*1.0-cm sized esophageal defect was identified during the emergency surgery. Complete healing of the esophageal defect was achieved by revision repair with reinforcement using local muscle flap. A 65-year-old man with a history of ankylosing spondylitis presented with severe dysphagia 1 year after C7 pedicle subtraction osteotomy, C2-T4 posterior instrumentation, and C6-C7 ACDF with a plate for a chin-on-chest deformity. Before closure, 1 cc of depomedrol had been placed into the wound. Eleven months postoperatively, he complained of new onset dysphagia. The endoscopic examination demonstrated an esophageal tear with visualization of the anterior cervical plate through the tear. Successful healing was possible with primary repair. CONCLUSIONS: Retropharyngeal steroids have been shown to decrease PSTS and dysphagia after anterior cervical spine surgery. We believe that it would be prudent to consider avoiding the RS use in patients with a history of chronic corticosteroid use and/or soft-tissue vulnerability or only to use them with caution. Any history of dysphagia that occurs weeks, months, or even years later should be investigated for the possibility of esophageal perforation. PMID- 26130085 TI - D-dimer screening for deep venous thrombosis in traumatic cervical spinal injuries. AB - BACKGROUND CONTEXT: Deep venous thrombosis (DVT) in spinal cord injury (SCI) patients is a life-threatening comorbidity. Despite its seriousness, prophylaxis and screening for DVT in SCI patients are still not sophisticated. PURPOSE: This study aimed to define the epidemiology and incidence of DVT in acute traumatic cervical SCI in a Japanese population, determine the best timing for DVT screening, and determine the optimal D-dimer threshold level for use as an easy and minimally invasive screening tool. STUDY DESIGN: This is a prospective clinical study. PATIENT SAMPLE: The patient sample included acute traumatic cervical SCI patients who were admitted to our facility within 2 weeks after injury. OUTCOME MEASURE: Multivariate logistic regression was performed for outcome measure. METHODS: We enrolled 268 patients (223 men and 45 women), from April 2007 to December 2012. After excluding early drop-out patients, 211 patients remained. Assessment for neurological status and blood chemistry, especially blood coagulation levels (prothrombin time, prothrombin time international normalized ratio, activated partial thromboplastin time, and serum D-dimer), was performed every week until 1 month after injury. Ultrasonography was performed for DVT detection every 2 weeks. RESULTS: Deep venous thromboses were detected in 22 patients (10.4% of patients studied). All DVT-positive patients demonstrated severe paralysis classified as C or greater on the American Spinal Injury Association (ASIA) Impairment Scale. Multivariate logistic regression of clinical and laboratory parameters revealed that only the D-dimer level at 2 weeks after injury was an accurate predictor of DVT formation. The optimal threshold of D-dimer for prediction was determined to be 16 MUg/dL. The sensitivity and specificity for detecting DVT were 77.3% and 69.2%, respectively. CONCLUSIONS: D-dimer levels may be used to predict the likelihood of DVT development in patients with acute cervical SCI. Furthermore, the optimal timing for screening test by D-dimer is 2 weeks after injury, and optimal threshold level for D-dimer for diagnosing DVT is 16 MUg/dL. Such a screening test would be cost-efficient and simple to administer and could then be followed with additional investigations, such as ultrasonography or venography. PMID- 26130086 TI - New Insight into the Role of the Calvin Cycle: Reutilization of CO2 Emitted through Sugar Degradation. AB - Ralstonia eutropha is a facultative chemolithoautotrophic bacterium that uses the Calvin-Benson-Bassham (CBB) cycle for CO2 fixation. This study showed that R. eutropha strain H16G incorporated (13)CO2, emitted by the oxidative decarboxylation of [1-(13)C1]-glucose, into key metabolites of the CBB cycle and finally into poly(3-hydroxybutyrate) [P(3HB)] with up to 5.6% (13)C abundance. The carbon yield of P(3HB) produced from glucose by the strain H16G was 1.2 times higher than that by the CBB cycle-inactivated mutants, in agreement with the possible fixation of CO2 estimated from the balance of energy and reducing equivalents through sugar degradation integrated with the CBB cycle. The results proved that the 'gratuitously' functional CBB cycle in R. eutropha under aerobic heterotrophic conditions participated in the reutilization of CO2 emitted during sugar degradation, leading to an advantage expressed as increased carbon yield of the storage compound. This is a new insight into the role of the CBB cycle, and may be applicable for more efficient utilization of biomass resources. PMID- 26130087 TI - Management of postpartum haemorrhage with uterine balloon tamponade: The way forward. AB - Uterine balloon tamponade has rapidly gained popularity in the management of postpartum haemorrhage. It is a conservative method often utilised before embarking on advanced surgical interventions. The mechanism of action, complications and long-term outcomes are discussed. PMID- 26130088 TI - Role of anoctamin-1 and bestrophin-1 in spinal nerve ligation-induced neuropathic pain in rats. AB - BACKGROUND: Calcium-activated chloride channels (CaCCs) activation induces membrane depolarization by increasing chloride efflux in primary sensory neurons that can facilitate action potential generation. Previous studies suggest that CaCCs family members bestrophin-1 and anoctamin-1 are involved in inflammatory pain. However, their role in neuropathic pain is unclear. In this investigation we assessed the involvement of these CaCCs family members in rats subjected to the L5/L6 spinal nerve ligation. In addition, anoctamin-1 and bestrophin-1 mRNA and protein expression in dorsal root ganglion (DRG) and spinal cord was also determined in the presence and absence of selective inhibitors. RESULTS: L5/L6 spinal nerve ligation induced mechanical tactile allodynia. Intrathecal administration of non-selective CaCCs inhibitors (NPPB, 9-AC and NFA) dose dependently reduced tactile allodynia. Intrathecal administration of selective CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) also dose-dependently diminished tactile allodynia and thermal hyperalgesia. Anoctamin-1 and bestrophin-1 mRNA and protein were expressed in the dorsal spinal cord and DRG of naive, sham and neuropathic rats. L5/L6 spinal nerve ligation rose mRNA and protein expression of anoctamin-1, but not bestrophin-1, in the dorsal spinal cord and DRG from day 1 to day 14 after nerve ligation. In addition, repeated administration of CaCCs inhibitors (T16Ainh-A01, CaCCinh-A01 or NFA) or anti-anoctamin-1 antibody prevented spinal nerve ligation-induced rises in anoctamin-1 mRNA and protein expression. Following spinal nerve ligation, the compound action potential generation of putative C fibers increased while selective CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) attenuated such increase. CONCLUSIONS: There is functional anoctamin-1 and bestrophin-1 expression in rats at sites related to nociceptive processing. Blockade of these CaCCs suppresses compound action potential generation in putative C fibers and lessens established tactile allodynia. As CaCCs activity contributes to neuropathic pain maintenance, selective inhibition of their activity may function as a tool to generate analgesia in nerve injury pain states. PMID- 26130089 TI - Mechanics and dynamics of reconstituted cytoskeletal systems. AB - The intracellular cytoskeleton is an active dynamic network of filaments and associated binding proteins that control key cellular properties, such as cell shape and mechanics. Due to the inherent complexity of the cell, reconstituted model systems have been successfully employed to gain an understanding of the fundamental physics governing cytoskeletal processes. Here, we review recent advances and key aspects of these reconstituted systems. We focus on the importance of assembly kinetics and dynamic arrest in determining network mechanics, and highlight novel emergent behavior occurring through interactions between cytoskeletal components in more complex networks incorporating multiple biopolymers and molecular motors. PMID- 26130090 TI - Monocyte Count and 30-Day Case Fatality in Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: Monocytes may contribute to secondary injury after intracerebral hemorrhage (ICH). We tested the association of absolute monocyte count with 30-day ICH case fatality in a multiethnic cohort. METHODS: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a prospective, multicenter, case-control study of ICH among white, black, and Hispanic patients. In 240 adults with nontraumatic ICH within 24 hours of symptom onset, we evaluated the influence of ICH score and complete blood count components on 30-day case fatality using generalized linear models. RESULTS: Mean age was 62.8 years (SD, 14 years); 61.7% were men, 33.3% black, and 29.6% Hispanic. Median ICH volume was 9.9 mL (interquartile range, 4.4-26.7). After adjusting for patient age and initial hemoglobin, higher total white blood cell count (P=0.0011), driven by higher absolute neutrophil count (P=0.002), was associated with larger ICH volume, whereas absolute monocyte count was not (P=0.15). After adjusting for age, Glasgow Coma Scale, ICH volume, location, and the presence or absence of intraventricular hemorrhage, baseline absolute monocyte count was independently associated with higher 30-day case-fatality (odds ratio, 5.39; 95% confidence interval, 1.87-15.49; P=0.0018), whereas absolute neutrophil count (odds ratio, 1.04; 0.46-2.32; P=0.93) and white blood cell count (odds ratio, 1.62; 0.58-4.54; P=0.36) were not. CONCLUSIONS: These data support an independent association between higher admission absolute monocyte count and 30-day case-fatality in ICH. Inquiry into monocyte-mediated pathways of inflammation and apoptosis may elucidate the basis for the observed association and may be targets for ICH neuroprotection. PMID- 26130091 TI - IL-4 Is Required for Sex Differences in Vulnerability to Focal Ischemia in Mice. AB - BACKGROUND AND PURPOSE: Interleukin (IL)-4 protects from middle cerebral artery occlusion in male mice. Females generally show less injury in response to the same ischemic challenge, but the underlying mechanisms are not fully understood. We tested the importance of IL-4 in female protection using IL-4 knockout (KO) mice. METHODS: IL-4 KO and wild-type (WT) mice of both sexes were subjected to middle cerebral artery occlusion. Infarct volume was assessed by triphenyltetrazolium chloride staining and neurobehavioral outcome by neuroscore. T cell proliferation was assessed after Concanavalin A exposure. Ischemic brain immune cell populations were analyzed by fluorescence-activated cell sorting and immunostaining. RESULTS: Infarction in WT females during estrus and proestrus phases was significantly smaller than in males; neurological score was better. Infarction volume was larger and neurological score worse in IL-4 KO compared with WT in both sexes, with no sex difference. Proliferation of T cells was inhibited in WT females with higher proliferation and no sex difference in IL-4 KO. Macrophage numbers and total T cells in the ischemic hemisphere were lower in WT females, and monocytes increased markedly in IL-4 KOs with no sex difference. The reduced macrophage infiltration in WT-females was predominantly M2. Loss of IL-4 increased CD68+ and iNOS+ cells and reduced YM1+ and Arg1+ cells in both sexes. CONCLUSIONS: IL-4 is required for female neuroprotection during the estrus phase of the estrus cycle. Protected WT females show a predominance of M2 activated microglia/macrophages and reduced inflammatory infiltration. Increasing macrophage M2 polarization, with or without added inhibition of infiltration, may be a new approach to stroke treatment. PMID- 26130092 TI - Effects of Centralizing Acute Stroke Services on Stroke Care Provision in Two Large Metropolitan Areas in England. AB - BACKGROUND AND PURPOSE: In 2010, Greater Manchester and London centralized acute stroke care into hyperacute units (Greater Manchester=3, London=8), with additional units providing ongoing specialist stroke care nearer patients' homes. Greater Manchester patients presenting within 4 hours of symptom onset were eligible for hyperacute unit admission; all London patients were eligible. Research indicates that postcentralization, only London's stroke mortality fell significantly more than elsewhere in England. This article attempts to explain this difference by analyzing how centralization affects provision of evidence based clinical interventions. METHODS: Controlled before and after analysis was conducted, using national audit data covering Greater Manchester, London, and a noncentralized urban comparator (38 623 adult stroke patients, April 2008 to December 2012). Likelihood of receiving all interventions measured reliably in pre- and postcentralization audits (brain scan; stroke unit admission; receiving antiplatelet; physiotherapist, nutrition, and swallow assessments) was calculated, adjusting for age, sex, stroke-type, consciousness, and whether stroke occurred in-hospital. RESULTS: Postcentralization, likelihood of receiving interventions increased in all areas. London patients were overall significantly more likely to receive interventions, for example, brain scan within 3 hours: Greater Manchester=65.2% (95% confidence interval=64.3-66.2); London=72.1% (71.4 72.8); comparator=55.5% (54.8-56.3). Hyperacute units were significantly more likely to provide interventions, but fewer Greater Manchester patients were admitted to these (Greater Manchester=39%; London=93%). Differences resulted from contrasting hyperacute unit referral criteria and how reliably they were followed. CONCLUSIONS: Centralized systems admitting all stroke patients to hyperacute units, as in London, are significantly more likely to provide evidence based clinical interventions. This may help explain previous research showing better outcomes associated with fully centralized models. PMID- 26130093 TI - Response to Letter Regarding Article, "Type of Anesthesia and Differences in Clinical Outcome After Intra-Arterial Treatment for Ischemic Stroke". PMID- 26130095 TI - Halfway Through an Amazing Journey. PMID- 26130096 TI - Letter by Schonenberger et al Regarding Article, "Type of Anesthesia and Differences in Clinical Outcome After Intra-Arterial Treatment for Ischemic Stroke". PMID- 26130094 TI - Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study. AB - BACKGROUND AND PURPOSE: The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. METHODS: The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. RESULTS: Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score >=3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). CONCLUSIONS: Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. PMID- 26130098 TI - Five-Year Outcome in Stroke Patients Submitted to Thrombolysis. AB - BACKGROUND AND PURPOSE: Little is known on long-term follow-up after thrombolysis in ischemic stroke patients because the majority of studies evaluated outcome at 3 to 12 months. We aimed to assess 5-year outcome after intravenous thrombolysis (IVT). METHODS: Cohort study based on the prospective registry of all consecutive ischemic stroke patients submitted to IVT in our Stroke Unit. Five-year outcome, including living settings, functional outcome, stroke recurrence, and mortality, was ascertained by telephonic interviews and additional review of clinical records. Multivariate analyses were performed to identify predictors of outcome and mortality. Excellent outcome was defined as modified Rankin scale 0 to 1. RESULTS: Five-year outcome was available for 155/164 patients submitted to IVT. At 5 years, 32.9% of patients had an excellent outcome (95% confidence interval (CI) =25.5-43.3) and mortality was 43.9% (95%CI=36.1-51.7). Increasing age (odds ratio =0.93, 95% CI =0.90-0.97) and increasing National Institute of Health Stroke Scale (NIHSS) 24 h after thrombolysis (odds ratio =0.81, 95% CI =0.74 0.90) were independently associated with a lower likelihood of an excellent 5 year outcome. Age (hazards ratio =1.07, 95% CI =1.03-1.11) and excellent functional outcome 3 months after thrombolysis (hazards ratio =0.28, 95%CI=0.12 0.66) were independently associated with mortality during follow-up. CONCLUSIONS: One third of ischemic stroke patients have excellent 5-year outcome after IVT. Younger age, lower NIHSS 24 h after IVT, and excellent 3-month functional outcome are independent predictors of excellent 5-year outcome. PMID- 26130097 TI - Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study. AB - BACKGROUND AND PURPOSE: Chronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors. METHODS: The study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates. RESULTS: In 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin-angiotensin system did not decrease stroke risk in individuals with albuminuria. CONCLUSIONS: Proteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation. PMID- 26130100 TI - CORRECTIONS. PMID- 26130099 TI - The High Life: Alpine Dwarfism in Arabidopsis. PMID- 26130101 TI - CORRECTIONS. PMID- 26130102 TI - CORRECTIONS. PMID- 26130103 TI - Erratum to: Purinergic P2X7 receptors regulate secretion of interleukin-1 receptor antagonist and beta cell function and survival. PMID- 26130104 TI - The effectiveness of exercise for the management of musculoskeletal disorders and injuries of the elbow, forearm, wrist, and hand: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration. AB - OBJECTIVE: The purpose of this systematic review was to evaluate the effectiveness of exercise compared to other interventions, placebo/sham intervention, or no intervention in improving self-rated recovery, functional recovery, clinical, and/or administrative outcomes in individuals with musculoskeletal disorders and injuries of the elbow, forearm, wrist, and hand. METHODS: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Paired reviewers independently screened studies for relevance and assessed the risk of bias using the Scottish Intercollegiate Guidelines Network criteria. We synthesized the evidence using the best evidence synthesis methodology. RESULTS: We identified 5 studies with a low risk of bias. Our review suggests that, for patients with persistent lateral epicondylitis, (1) adding concentric or eccentric strengthening exercises to home stretching exercises provides no additional benefits; (2) a home program of either eccentric or concentric strengthening exercises leads to similar outcomes; (3) home wrist extensor strengthening exercises lead to greater short-term improvements in pain reduction compared to "wait and see"; and (4) clinic-based, supervised exercise may be more beneficial than home exercises with minimal improvements in pain and function. For hand pain of variable duration, supervised progressive strength training added to advice to continue normal physical activity provides no additional benefits. CONCLUSION: The relative effectiveness of stretching vs strengthening for the wrist extensors remains unknown for the management of persistent lateral epicondylitis. The current evidence shows that the addition of supervised progressive strength training does not provide further benefits over advice to continue normal physical activity for hand pain of variable duration. PMID- 26130105 TI - Impact of Exposure to Childhood Maltreatment on Transitions to Alcohol Dependence in Women and Men. AB - BACKGROUND: Childhood maltreatment decreases age of first use and speeds the transition from first use to dependence (i.e., telescoping) for alcohol use, however, it is currently unknown whether this influence is the same for men and women. METHOD: Analyses were conducted with the National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,653). Outcome variables included age of alcohol initiation and time to onset of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence. Predictor variables included gender and childhood maltreatment. Linear and Poisson regression analyses were conducted. RESULTS: Results demonstrated that in regard to age of drinking initiation, individuals who experienced childhood maltreatment initiated 1 year earlier than those without maltreatment, however, there was no interaction of this relationship with gender. Regarding the time to dependence, it was found that women who experienced childhood maltreatment demonstrated telescoping (shorter time between onset and dependence) compared to women without maltreatment and men (both with and without maltreatment). CONCLUSION: Women with a history of childhood maltreatment are particularly vulnerable to an accelerated time from initiation of alcohol use until dependence, a pattern indicative of increased negative alcohol-related outcomes. Findings highlight the need for development of gender-specific prevention efforts and behavioral treatments to aid in early intervention of problematic alcohol use in women. PMID- 26130109 TI - [Alcohol in old age: Drinking habits, low risk drinking and alcohol-related disorders]. AB - Alcohol abuse and health problems due to alcohol increase in the elderly. The functional impact is more pronounced than in younger people; nevertheless, alcohol abuse in the elderly is often overlooked. Early onset and late onset alcoholics differ with respect to previous problems, social and health status and therapy prognosis. The severity of withdrawal depends on addiction severity and comorbidities but not on calendar age. It is important to support patients in developing a motivation for change. Brief interventions are effective in elderly persons with an at-risk consumption of alcohol. Guidelines for low risk alcohol consumption recommend two alcohol-free days per week. There is no evidence for the popular hypothesis of the beneficial effects of light to moderate drinking. This hypothesis was drawn from former observational studies but recent large and more thorough methodical studies suggest that these former results were due to statistical bias. Alcohol consumption is a matter of pleasure and not a matter of medical treatment or prevention. The new German guidelines on "Screening, assessment and treatment of alcohol use disorders" contain for the first time a special chapter on the elderly. PMID- 26130106 TI - Diagnostic assessment of osteosarcoma chemoresistance based on Virtual Clinical Trials. AB - Osteosarcoma is the most common primary bone tumor in pediatric and young adult patients. Successful treatment of osteosarcomas requires a combination of surgical resection and systemic chemotherapy, both neoadjuvant (prior to surgery) and adjuvant (after surgery). The degree of necrosis following neoadjuvant chemotherapy correlates with the subsequent probability of disease-free survival. Tumors with less than 10% of viable cells after treatment represent patients with a more favorable prognosis. However, being able to predict early, such as at the time of the pre-treatment tumor biopsy, how the patient will respond to the standard chemotherapy would provide an opportunity for more personalized patient care. Patients with unfavorable predictions could be studied in a protocol, rather than a standard setting, towards improving therapeutic success. The onset of necrotic cells in osteosarcomas treated with chemotherapeutic agents is a measure of tumor sensitivity to the drugs. We hypothesize that the remaining viable cells, i.e., cells that have not responded to the treatment, are chemoresistant, and that the pathological characteristics of these chemoresistant tumor cells within the osteosarcoma pre-treatment biopsy can predict tumor response to the standard-of-care chemotherapeutic treatment. This hypothesis can be tested by comparing patient histopathology samples before, as well as after treatment to identify both morphological and immunochemical cellular features that are characteristic of chemoresistant cells, i.e., cells that survived treatment. Consequently, using computational simulations of dynamic changes in tumor pathology under the simulated standard of care chemotherapeutic treatment, one can couple the pre- and post-treatment morphological and spatial patterns of chemoresistant cells, and correlate them with patient clinical diagnoses. This procedure, that we named 'Virtual Clinical Trials', can serve as a potential predictive biomarker providing a novel value-added decision support tool for oncologists. PMID- 26130110 TI - Thiazide Diuretics in the Management of Young Children with Central Diabetes Insipidus. AB - OBJECTIVE: To report our experience in treating infants and toddlers with central diabetes insipidus (DI) with thiazide diuretics. STUDY DESIGN: A retrospective chart review of all infants and toddlers who were treated with thiazide diuretics for central DI at the Mayo Clinic between 1996 and 2014. RESULTS: Our cohort consisted of 13 patients. The median age at the start of therapy was 6 months (IQR, 1-14 months). Eight patients were given chlorothiazide at a starting dose of 5-10 mg/kg/day, and 5 patients were treated with hydrochlorothiazide at a starting dose of 1-2 mg/kg/day. The median age at the cessation of thiazide therapy was 18 months (IQR, 11.5-39 months). The main reason for stopping was the lack of continued response, in addition to hypernatremia. There was no hospitalization secondary to hyponatremia and only 1 hospitalization secondary to hypernatremia while receiving thiazide therapy. Calcium was checked periodically in 7 of the 13 patients, and 2 of these 7 patients had persistent hypercalcemia. CONCLUSION: Thiazide diuretics appear to be safe and effective in treating infants with central DI. They can be continued after the introduction of solid food, and until a lack of response is observed. PMID- 26130111 TI - Gestational Weight Gain in Adolescent Compared with Adult Pregnancies: An Age Specific Body Mass Index Approach. AB - OBJECTIVE: To determine current trends in gestational weight gain (GWG) in adolescents, using adolescent specific body mass index (BMI), in relation to the 2009 Institute of Medicine GWG guidelines. STUDY DESIGN: Population-based retrospective cohort using Ohio birth records (2006-2012). Analyses were limited to primiparous women with singleton nonanomalous live births and available data on BMI and GWG. GWG percentiles were stratified by maternal age (less than 15, 15 17, 18-19, and 20-34 years old) and prepregnancy BMI category. Adolescent specific BMI definitions were used for mothers less than 19 years. RESULTS: A total of 1,034,552 births occurred during the study period; 326,368 were included for analysis. Less than one-quarter of women gained the recommended amount of weight (20.6%). A large proportion of pregnancies had excessive GWG: 59.8% of mothers less than 15 years of age, compared with older adolescent (59.9%, 62.6%) and adult mothers (64.6%), P < .001. Average, median, and IQRs of GWG were similar for all women within the same BMI category, regardless of age. Except in underweight women, the average GWG was at the high end or above the 2009 Institute of Medicine recommendations, for adolescents in all BMI groups, similar to adults, median 35 (IQR 24-47) pounds. CONCLUSIONS: Current GWG trends indicate that excessive weight gain is nearly as common in adolescents as in adult mothers. PMID- 26130112 TI - Renin Angiotensin System Blocker Fetopathy: A Midwest Pediatric Nephrology Consortium Report. AB - OBJECTIVES: Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. STUDY DESIGN: This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. RESULTS: Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. CONCLUSION: RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age. PMID- 26130113 TI - Intestinal Microbiota, Lipids, and the Pathogenesis of Intestinal Failure Associated Liver Disease. PMID- 26130114 TI - A quantitative assessment of bone area increase due to ornamentation in the Crocodylia. AB - Bone ornamentation, in the form of highly repetitive motives created by pits and ridges, is a frequent feature on vertebrate skull roofs and osteoderms. The functional significance of this character remains a matter of controversy and speculation. The many diverging hypotheses proposed to explain it all share a common logical prerequisite: bone ornamentation should increase significantly the surface area of the bones that bear it. In order to test this assumption in the Crocodylia, we developed a method for quantifying the gain in area due to ornamentation using a three-dimensional-surface scanner. On crocodylian osteoderms, the gain in area can be up to 40%, and on the cranial table, it ranges between 10 and 32% in adult specimens (in both cases, it shows substantial differences between the adults of the various species included in the sample). Area gain on the snout is lesser (0-20% in adults), and more variable between species. In general, bone ornamentation is less pronounced, and results in fewer area gains in juvenile specimens. The main morphometric results yielded by this study are discussed in reference to the few comparative data available hitherto, and to the functional interpretations proposed by previous authors. PMID- 26130115 TI - Valorization of Pomace Powder Obtained from Native Mexican Apple (Malus domestica var. rayada): Chemical, Techno-functional and Antioxidant Properties. AB - The aims of the work were to determine the chemical, techno-functional and antioxidant properties of native Mexican apple pomace powder (MAPP) obtained from cider industry. The proximate composition and the total, insoluble and soluble dietary fibre content were determined, as well as the water holding (WHC), oil holding (OHC), swelling (SWC) capacities and the polyphenolic profile. For antioxidant activity, three different test systems were used (DPPH, FIC and FRAP). The total, insoluble and soluble dietary fiber content of MAPP was 70.91, 48.43 and 22.48 g/100 g, respectively. MAPP had a WHC, OHC and SWC of 4.2 g water/g sample, 1.69 g oil/g sample and 3.2 mL/g sample, respectively. Polyphenolic profile showed 10 flavonoid compounds identified mainly quercetin glycosides. MAPP showed good antioxidant activity with high correlation between total phenolic compounds and antioxidant capacity. The results obtained showed that MAPP could be considered a good source of bioactive compounds with significant antioxidant activity. PMID- 26130116 TI - Additional value of associating aortic valve calcification to coronary calcium as a gatekeeper for coronary tomography angiography. AB - BACKGROUND: Aortic valve calcification shares risk factors with coronary artery disease. Coronary calcium has been used has a gatekeeper to performing coronary tomography angiography. The aim of this study was to evaluate aortic valve calcification as a predictor of obstructive coronary artery disease by computed tomography, and its possible usefulness, alongside with coronary calcium, to improve the decision of whether or not to proceed with computed tomography angiography. METHODS: Transversal case-control study including 154 consecutive patients (62 +/- 12 years, 57.6 % female, without known coronary or valve disease) undergoing calcium scoring and angiography through computed tomography (Phillips Brilliance, 16-slice). Predictors of aortic valve calcification and obstructive coronary artery disease were identified. Usefulness of aortic valve calcification when added to calcium score for prediction of obstructive coronary artery disease was assessed by binary logistic regression and net reclassification index. RESULTS: Aortic valve calcification was associated with higher coronary calcium, extent and prevalence of obstructive coronary disease, which was identified in 22.1 % of patients and was discriminated by aortic valve calcium with an area under curve 0.749 (p < 0.001, Youden index: 61). A higher discriminative power was achieved with a model based on coronary and aortic valve calcification (AUC 0.900, p < 0.001). Compared with calcium score >400 as a gatekeeper to angiography, the association of aortic calcium >61 allowed a net reclassification index of +7.7 % of patients. CONCLUSIONS: Aortic valve calcification is associated with the prevalence and extent of obstructive coronary artery disease by computed tomography angiography and is an easy, fast and useful method to improve the selection of patients for angiography. PMID- 26130117 TI - A community-based cross-sectional study of the epidemiology of onchocerciasis in unmapped villages for community directed treatment with ivermectin in Jimma Zone, southwestern Ethiopia. AB - BACKGROUND: Human onchocerciasis is a neglected tropical parasitic disease caused by Onchocerca volvulus (O. volvulus) that may result in devastating skin and eye morbidity. Even though the disease is targeted for elimination, there was little or no information on the level of onchocerciasis endemicity for implementation of community directed treatment with ivermectin (CDTI) in the current study area. Thus, this study aimed at investigating the epidemiology of onchocerciasis and the level of awareness towards the disease among communities living close to CDTI area, Jimma Zone, southwestern Ethiopia. METHODS: A community based cross sectional study was conducted from April 23 to May 22, 2012. Data on socio demographic characteristics, knowledge, attitude and practice towards onchocerciasis were collected using semi-structured questionnaires. Clinical examination was undertaken for onchocercal skin diseases by experienced health professionals. Moreover, two skin snip samples were collected from the right and left gluteal folds. Study participants found positive for O. volvulus infection during the study were treated individually with standard dose of ivermectin as per WHO guideline. RESULTS: The overall prevalence of O. volvulus infection was 22.5 % while the prevalence of onchocercal skin diseases was 29.8 %. The community microfilarial (mf) load was 5.70 mf per skin snip. Age, sex, educational status, occupation and duration of stay in the villages showed significant association with onchocerciasis (P < 0.05). But sex (OR = 0.565, 95 % CI = 0.335, 0.952), educational status (OR = 0.545, 95 % CI = 0.310, 0.958) and duration of stay in the village (OR = 5.933, 95 % CI = 1.017, 34.626) were the independent predictors for O. volvulus infection. Three hundred eighty eight (88.2 %) of the study participants reported that they didn't know about onchocerciasis. CONCLUSIONS: There was moderate prevalence of onchocercal infection and onchocercial skin diseases (OSD) in the study area. Result of this study may suggest that the endemicity level of onchocerciasis in the study area was mesoendemic. Hence, intervention using ivermectin treatment should be implemented to reduce the burden of onchocerciasis. Since the majorities of the population had poor knowledge, attitude and practice towards onchocerciasis, inclusion of health education in the intervention package is crucial. PMID- 26130118 TI - Mitomycin-Induced Pulmonary Veno-Occlusive Disease: Evidence From Human Disease and Animal Models. AB - BACKGROUND: Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension characterized by the obstruction of small pulmonary veins and a dismal prognosis. PVOD may be sporadic or heritable because of biallelic mutations of the EIF2AK4 gene coding for GCN2. Isolated case reports suggest that chemotherapy may be a risk factor for PVOD. METHODS AND RESULTS: We reported on the clinical, functional, and hemodynamic characteristics and outcomes of 7 cases of PVOD induced by mitomycin-C (MMC) therapy from the French Pulmonary Hypertension Registry. All patients displayed squamous anal cancer and were treated with MMC alone or MMC plus 5-fluoruracil. The estimated annual incidence of PVOD in the French population that have anal cancer is 3.9 of 1000 patients, which is much higher than the incidence of PVOD in the general population (0.5/million per year). In rats, intraperitoneal administration of MMC induced PVOD, as demonstrated by pulmonary hypertension at right-heart catheterization at days 21 to 35 and major remodeling of small pulmonary veins associated with foci of intense microvascular endothelial-cell proliferation of the capillary bed. In rats, MMC administration was associated with dose-dependent depletion of pulmonary GCN2 content and decreased smad1/5/8 signaling. Amifostine prevented the development of MMC-induced PVOD in rats. CONCLUSIONS: MMC therapy is a potent inducer of PVOD in humans and rats. Amifostine prevents MMC-induced PVOD in rats and should be tested as a preventive therapy for MMC-induced PVOD in humans. MMC induced PVOD in rats represents a unique model to test novel therapies in this devastating orphan disease. PMID- 26130120 TI - Longitudinal Strain in Heart Failure With Preserved Ejection Fraction: Is There a Role for Prognostication? PMID- 26130119 TI - Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone. AB - BACKGROUND: Impairment in left ventricular systolic function has been described in heart failure (HF) with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether left ventricular longitudinal strain (LS) is predictive of cardiovascular outcomes in HFpEF beyond clinical and conventional echocardiographic measures. METHODS AND RESULTS: LS was assessed by 2-dimensional speckle-tracking echocardiography at baseline in 447 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 years (interquartile range, 1.5-3.9 years), 115 patients experienced the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS <15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted hazard ratio, 2.14; 95% confidence interval, 1.26-3.66; P=0.005), cardiovascular death alone (adjusted hazard ratio, 3.20; 95% confidence interval, 1.44-7.12; P=0.004), and HF hospitalization alone (adjusted hazard ratio, 2.23; 95% confidence interval, 1.16-4.28; P=0.016) after adjustment for clinical and conventional echocardiographic variables. LS was the strongest echocardiographic predictor of the composite outcome. Exploratory analysis in a subset of 131 patients with follow-up LS assessed after 12 to 18 months demonstrated a trend toward improvement in LS associated with spironolactone in patients enrolled in the Americas but not in Russia or Georgia. CONCLUSIONS: Impaired left ventricular systolic function is a powerful predictor of HF hospitalization, cardiovascular death, or aborted cardiac arrest in HFpEF independent of clinical predictors. Impaired LS represents a novel imaging biomarker to identify patients with HFpEF at particularly high risk for cardiovascular morbidity and mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302. PMID- 26130121 TI - American Heart Association Response to the 2015 Institute of Medicine Report on Strategies to Improve Cardiac Arrest Survival. AB - The American Heart Association (AHA) commends the recently released Institute of Medicine (IOM) report, Strategies to Improve Cardiac Arrest Survival: A Time to Act (2015). The AHA recognizes the unique opportunity created by the report to meaningfully advance the objectives of improving outcomes for sudden cardiac arrest. For decades, the AHA has focused on the goal of reducing morbidity and mortality from cardiovascular disease though robust support of basic, translational, clinical, and population research. The AHA also has developed a rigorous process using the best available evidence to develop scientific, advisory, and guideline documents. These core activities of development and dissemination of scientific evidence have served as the foundation for a broad range of advocacy initiatives and programs that serve as a foundation for advancing the AHA and IOM goal of improving cardiac arrest outcomes. In response to the call to action in the IOM report, the AHA is announcing 4 new commitments to increase cardiac arrest survival: (1) The AHA will provide up to $5 million in funding over 5 years to incentivize resuscitation data interoperability; (2) the AHA will actively pursue philanthropic support for local and regional implementation opportunities to increase cardiac arrest survival by improving out of-hospital and in-hospital systems of care; (3) the AHA will actively pursue philanthropic support to launch an AHA resuscitation research network; and (4) the AHA will cosponsor a National Cardiac Arrest Summit to facilitate the creation of a national cardiac arrest collaborative that will unify the field and identify common goals to improve survival. In addition to the AHA's historic and ongoing commitment to improving cardiac arrest care and outcomes, these new initiatives are responsive to each of the IOM recommendations and demonstrate the AHA's leadership in the field. However, successful implementation of the IOM recommendations will require a timely response by all stakeholders identified in the report and a coordinated approach to achieve our common goal of improved cardiac arrest outcomes. PMID- 26130122 TI - Mast cell stabilisers. AB - Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators are implicated in many different conditions including allergic rhinitis, conjunctivitis, asthma, psoriasis, mastocytosis and the progression of many different cancers. Thus, there is intense interest in the development of agents which prevent mast cell mediator release or which inhibit the actions of such mediators once released into the environment of the cell. Much progress into the design of new agents has been made since the initial discovery of the mast cell stabilising properties of khellin from Ammi visnaga and the clinical approval of cromolyn sodium. This review critically examines the progress that has been made in the intervening years from the design of new agents that target a specific signalling event in the mast cell degranulation pathway to those agents which have been developed where the precise mechanism of action remains elusive. Particular emphasis is also placed on clinically used drugs for other indications that stabilise mast cells and how this additional action may be harnessed for their clinical use in disease processes where mast cells are implicated. PMID- 26130123 TI - The high-affinity immunoglobulin E receptor as pharmacological target. AB - The high-affinity receptor for immunoglobulin E is expressed mainly on mast cells and basophils, but also on neutrophils, eosinophils, platelets, monocytes, Langerhans and dendritic cells, airway smooth muscle cells and some nerve cells. Its main function is, upon its engagement by IgE and specific antigen, to trigger a powerful defense against invading pathogens and a rapid neutralization of dangerous toxic substances introduced in the body. This powerful response could be wielded against tumors. But, when control over this receptor is lost, its unchecked activation can induce an array of diseases, some of which can lead to death. In this review we will summarize the pharmacological approaches and strategies that are currently used, or under study, to harness or wield activation of this receptor for therapeutic purposes. PMID- 26130124 TI - Microbes taming mast cells: Implications for allergic inflammation and beyond. AB - There is increasing awareness of a relationship between our microbiota and the pathogenesis of allergy and other inflammatory diseases. In investigating the mechanisms underlying microbiota modulation of allergy the focus has been on the induction phase; alterations in the phenotype and function of antigen presenting cells, induction of regulatory T cells and shifts in Th1/Th2 balance. However there is evidence that microbes can influence the effector phase of disease, specifically that certain potentially beneficial bacteria can attenuate mast cell activation and degranulation. Furthermore, it appears that different non pathogenic bacteria can utilize distinct mechanisms to stabilize mast cells, acting locally though direct interaction with the mast cell at mucosal sites or attenuating systemic mast cell dependent responses, likely through indirect signaling mechanisms. The position of mast cells on the frontline of defense against pathogens also suggests they may play an important role in fostering the host-microbiota relationship. Mast cells are also conduits of neuro-immuo endocrine communication, suggesting the ability of microbes to modulate cell responses may have implications for host physiology beyond immunology. Further investigation of mast cell regulation by non-pathogenic or symbiotic bacteria will likely lead to a greater understanding of host microbiota interaction and the role of the microbiome in health and disease. PMID- 26130125 TI - A comparative study on the cardioprotective potential of atorvastatin and simvastatin in hyperhomocysteinemic rat hearts. AB - The present study has been deliberated in order to compare the cardioprotective potential of 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, Atorvastatin and Simvastatin in hyperhomocysteinemic rat hearts. L-methionine (1.7 g/kg/day orally) was administered to rats for 4 weeks to produce experimental hyperhomocysteinemia (Hhcy). Isolated Langendorff-perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. The extent of myocardial damage was assessed in terms of myocardial infarct size using triphenyltetrazolium chloride (TTC) staining, and release of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary effluent; whereas the oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation and reduced glutathione. Ischemia-reperfusion (I/R) was noted to produce myocardial injury in normal and hyperhomocysteinemic rat hearts, assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent and oxidative stress. Treatment with Atorvatstain (50 uM) and Simvastatin (10 uM) afforded cardioprotection against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts as assessed in terms of reductions in myocardial infarct size, LDH and CK levels in coronary effluent and oxidative stress. It may be concluded that reductions in the high degree of oxidative stress may be responsible for the observed cardioprotective potential of Atorva-and Simvastatin, and both statins can be used interchangeably to afford cardioprotection against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts. PMID- 26130126 TI - A prospective assessment of cardiac biomarkers for hemodynamic stress and necrosis and the risk of falls among older people: the ActiFE study. AB - Falls are related to a complex interaction of risk factors. We examined if cardiac biomarkers for hemodynamic stress (N-terminal pro Brain Natriuretic Peptide-NT-proBNP), and for necrosis [high sensitive (hs) cardiac troponins T (cTnT) and I (cTnI)] are associated with falls in older people. Biomarkers were measured at baseline in a cohort of 1506 community-dwelling adults >=65 years. Falls were assessed prospectively in a falls calendar (median 370 days). Cox proportional hazards models evaluated the association of each biomarker with the incidence of the first fall accounting for established confounders. We observed 430 incident falls among 1327 participants and an effect modification by sex for all biomarkers. In multivariable analyses among men a one unit increment of log transformed hs-cTnI was associated with a hazard ratio (HR) of 1.26 (95 % CI 1.04, 1.53). Men with hs-cTnT >= 14 ng/L had a HR of 1.74 (95 % CI 1.15, 2.61) compared to those with undetectable hs-cTnT levels. In women cTn were not associated with falls. We did not detect an association between NT-proBNP and the risk of fall. Our results suggest that cardiac troponins may not only identify subjects at risk for cardiovascular diseases, but also help to understand the underlying complex pathophysiology of falls. PMID- 26130127 TI - Personality traits and the risk for Parkinson disease: a prospective study. AB - In this study, we explored the association between the personality traits, neuroticism and introversion, and risk of Parkinson disease (PD). A population based cohort study was conducted using questionnaire data from the Swedish Twin Registry for twins born 1926-1958 (n > 29,000). Personality traits were assessed in 1973 by a short form of Eysenck's Personality Inventory. The cohort was followed from 1974 to 2012 through Swedish patient and cause of death registers for PD ascertainment. Cox proportional hazards regression was used to estimate subsequent risk of PD, adjusting for attained age, sex and smoking. A mediation analysis was performed to further explore the role of smoking in the relationship between personality trait and PD. Confounding by familial factors was explored using a within-pair analysis. During a mean follow-up time of 36.8 years, 197 incident PD cases were identified. Both neuroticism and introversion were associated with an increased risk of PD after adjustment. Smoking was a significant mediator in the relationship between personality traits and PD that partly accounted for the effect of introversion, whereas it acted as a suppressor for the effect of neuroticism on PD risk. In the within-pair analyses, associations for neuroticism and introversion were attenuated. In conclusion, our study provides evidence that neuroticism is associated with an increased risk of PD that is in part suppressed by smoking. There was a weak association between introversion and PD and this effect was at least partly mediated through smoking. The observed effects may partly be explained by familial factors shared by twins. PMID- 26130128 TI - A prospective cohort study of the combined effects of physical activity and anthropometric measures on the risk of post-menopausal breast cancer. AB - Although keeping a healthy weight and being physically active are among the few modifiable risk factors for post-menopausal breast cancer, the possible interaction between these two risk factors remains to be established. We analyzed prospectively a cohort of 19,196 women who provided detailed self-report on anthropometric measures, physical activity and possible confounders at enrollment in 1997. We achieved complete follow-up through 2010 and ascertained 609 incident cases of post-menopausal invasive breast cancer. We calculated metabolic energy turnover (MET h/day) per day and fitted Cox proportional hazards models to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs). The incidence of post-menopausal breast cancer among obese women (BMI >= 30 kg/m(2)) was 58 % higher (HR 1.58, CI 1.16-2.16) than in women of normal weight (18.5 <= BMI < 25). Women in the lowest tertile of total physical activity (< 31.2 MET h/day) had 40 % higher incidence of post-menopausal breast cancer (HR 1.40, CI 1.11-1.75) than those in the highest tertile (>= 38.2 MET h/day). The excess incidence linked to these two factors seemed to combine in an approximately additive manner; the incidence among the most obese and sedentary women was doubled (HR 2.07, CI 1.31 3.25) compared with the most physically active women with normal weight. No heterogeneity of the physical activity-linked risk ratios across strata of BMI was detected (p value for interaction = 0.98). This prospective study revealed dose-dependent, homogenous inverse associations between post-menopausal breast cancer incidence and physical activity across all strata of BMI, and between post menopausal breast cancer incidence and BMI across all strata of physical activity, with no evidence of additive or multiplicative interaction between the two, suggesting independent effects. PMID- 26130129 TI - Non-attendance in mammography screening and women's social network: a cohort study on the influence of family composition, social support, attitudes and cancer in close relations. AB - BACKGROUND: Mammography screening can reduce breast cancer mortality. The aim of the present study was to investigate non-attendance in mammography screening in relation to different aspects of a women's social network, attitudes and cancer in close relations. METHODS: Data from the Malmo Diet and Cancer Study baseline examination in 1991-1996 was used. A re-examination began in 2007, and 1452 women participated. Family composition, social support, sense of belonging, attitudes on screening and breast cancer risk and on previous cancer in close relations were investigated in relation to self-reported participation in mammography screening using logistic regression analysis, yielding odds ratios with 95 % confidence intervals. RESULTS: Both attendees (98.0 %) and non-attendees (95.2 %) considered mammography screening important. Non-attendance in mammography screening was associated with being unmarried vs. married (2.40:1.30-4.45) and with not having vs. having children (1.77:1.08-2.92). Non-attendees planned to abstain from mammography screening in the future more often than attendees (4.78:2.56-8.90), and they had often abstained from cervical cancer screening (1.69:1.04-2.75). No other statistically significant association was found. CONCLUSIONS: This study indicates that family composition, but not necessarily the presence or absence of social support, perceived cancer risk or cancer in close relations, may affect non-attendance in mammography screening. A positive attitude towards mammography screening was found among both attendees and non attendees, although the latter group planned to a lesser degree to attend mammography screening in the future. PMID- 26130130 TI - Surface ultrastructure and mechanical properties of three different white-coated NiTi archwires. AB - The recent trend in orthodontic treatment is to apply esthetic materials to orthodontic appliances with adequate clinical performance. The aim of this study was to investigate the ultrastructure (surface roughness) and mechanical properties (load-deflection curve) of three as-received, white-coated superelastic nickel-titanium (NiTi) archwires using atomic force microscopy (AFM) and modified three-point bending test assessments, respectively. Three representative esthetic NiTi archwires were used, silver-platinum- and polymer coated NiTi Natural Dany (Dany group), epoxy resin-coated Orthoforce UltraestheticTM (Ultra group), and Teflon(r)-coated Perfect (Perfect group). Uncoated metallic areas of each wire were used as controls. The diameter of the Perfect archwire was significantly larger than that of other archwires. The Dany and Ultra groups showed more deflection than the Perfect group. The hysteresis area of the Dany and Ultra groups showed approximately two- and fourfold increases compared to the control and the Perfect group. The Dany group (2037.5 +/- 527.3 nm) had the highest peak-to-peak surface roughness in the coated areas, followed by the Ultra group (811.1 +/- 407.5 nm) and the Perfect group (362.7 +/- 195.8 nm). However, reverse nanostructural changes in the surface roughness were observed in the uncoated metallic areas. The results suggested that the load deflection properties and the surface roughness of superelastic NiTi archwires were affected directly by the coating materials. Although the efficiency of orthodontic treatment was affected by various factors, when only considering the frictional force and mechanostructural properties, the epoxy resin-coated Orthoforce UltraestheticTM archwires were the most effective for orthodontic treatment. PMID- 26130131 TI - Utility of CD54, CD229, and CD319 for the identification of plasma cells in patients with clonal plasma cell diseases. AB - BACKGROUND: Multiparameter flow cytometry (MFC) identification and characterization of plasma cells (PCs) is a useful tool to support diagnosis, prognostication, and monitoring of PC diseases (PCD). Currently, the number of MFC markers suited for the identification of PC remains limited. Moreover, antibody therapies against PC-associated markers further compromise the utility of the most widely used reagents (e.g., CD38). Despite markers other than CD38 and CD138 are recognized as potentially useful PC-identification markers, no study has comparatively evaluated their performance in combination with CD38 and CD138. Here we compared the utility of CD229, CD54, and CD319 for the identification of normal and aberrant PCs. METHODS: Bone marrow (BM) samples from 5 healthy controls, two noninfiltrated nonHodgkin lymphoma cases and 46 PCD patients plus 3 extraosseous plasmocytomas, and normal peripheral blood (PB) specimens, were studied. RESULTS: Our results showed adequate performance of all three markers once combined with CD38. In contrast, when combined with CD138 for the identification of PC, only CD229 provided a good discrimination between PCs and all other cells for all BM and PB samples analyzed; in contrast, CD54 and CD319 showed limited utility for the identification of PCs, mainly because of significant overlap of the staining for these two markers on PCs and other myeloid cells in the sample. CONCLUSIONS: From the three markers evaluated, CD229 may be considered as the most reliable marker to replace CD38 or CD138 for the identification of PCs in patients undergoing anti-CD38 or anti-CD138 therapy, until a better alternative is available. PMID- 26130132 TI - BioMaS: a modular pipeline for Bioinformatic analysis of Metagenomic AmpliconS. AB - BACKGROUND: Substantial advances in microbiology, molecular evolution and biodiversity have been carried out in recent years thanks to Metagenomics, which allows to unveil the composition and functions of mixed microbial communities in any environmental niche. If the investigation is aimed only at the microbiome taxonomic structure, a target-based metagenomic approach, here also referred as Meta-barcoding, is generally applied. This approach commonly involves the selective amplification of a species-specific genetic marker (DNA meta-barcode) in the whole taxonomic range of interest and the exploration of its taxon-related variants through High-Throughput Sequencing (HTS) technologies. The accessibility to proper computational systems for the large-scale bioinformatic analysis of HTS data represents, currently, one of the major challenges in advanced Meta barcoding projects. RESULTS: BioMaS (Bioinformatic analysis of Metagenomic AmpliconS) is a new bioinformatic pipeline designed to support biomolecular researchers involved in taxonomic studies of environmental microbial communities by a completely automated workflow, comprehensive of all the fundamental steps, from raw sequence data upload and cleaning to final taxonomic identification, that are absolutely required in an appropriately designed Meta-barcoding HTS based experiment. In its current version, BioMaS allows the analysis of both bacterial and fungal environments starting directly from the raw sequencing data from either Roche 454 or Illumina HTS platforms, following two alternative paths, respectively. BioMaS is implemented into a public web service available at https://recasgateway.ba.infn.it/ and is also available in Galaxy at http://galaxy.cloud.ba.infn.it:8080 (only for Illumina data). CONCLUSION: BioMaS is a friendly pipeline for Meta-barcoding HTS data analysis specifically designed for users without particular computing skills. A comparative benchmark, carried out by using a simulated dataset suitably designed to broadly represent the currently known bacterial and fungal world, showed that BioMaS outperforms QIIME and MOTHUR in terms of extent and accuracy of deep taxonomic sequence assignments. PMID- 26130133 TI - Risk factors for postoperative sepsis in laparoscopic gastric bypass. AB - INTRODUCTION: Postoperative sepsis is a rare but serious complication following elective surgery. The purpose of this study was to identify the rate of postoperative sepsis following elective laparoscopic gastric bypass (LGBP) and to identify patients' modifiable, preoperative risk factors. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2013 for factors associated with the development of postoperative sepsis following elective LGBP. Patients who developed sepsis were compared to those who did not. Results were analyzed using the Chi-square test for categorical variables and Wilcoxon two-sample test for continuous variables. A multivariate logistic regression analysis was utilized to calculate adjusted odds ratios for factors contributing to sepsis. RESULTS: During the study period, 66,838 patients underwent LGBP. Of those, 546 patients developed postoperative sepsis (0.82%). The development of sepsis was associated with increased operative time (161 +/- 77.8 vs. 135.10 +/- 56.5 min; p < 0.0001) and a greater number of preoperative comorbidities, including diabetes (39.6 vs. 30.6%; p < 0.0001), hypertension requiring medication (65.2 vs. 54%; p < 0.0001), current tobacco use (16.7 vs. 11.5%; p = 0.0002), and increased pack-year history of smoking (8.6 +/- 18.3 vs. 5.6 +/- 14.2; p = 0.0006), and the Charlson Comorbidity Index (0.51 +/- 0.74 vs. 0.35 +/- 0.57, p < 0.0001). Sepsis resulted in an increased length of stay (10.1 +/- 14.4 vs. 2.4 +/- 4.8 days; p < 0.0001) and a 30 times greater chance of 30-day mortality (4.03 vs. 0.11%, p < 0.0001). Multivariate logistic regression analysis showed that current smokers had a 63% greater chance of developing sepsis compared to non-smokers, controlling for age, race, gender, BMI, and CCI score (OR 1.63, 95% CI 1.23-2.14; p = 0.0006). CONCLUSIONS: Laparoscopic gastric bypass is uncommonly associated with postoperative sepsis. When it occurs, it portends a 30 times increased risk of death. A patient history of diabetes, hypertension, and increasing pack-years of smoking portend an increased risk of sepsis. Current smoking status, a preoperative modifiable risk factor, is independently associated with the chance of postoperative sepsis. Preoperative patient optimization and risk reduction should be a priority for elective surgery, and patients should be encouraged to stop smoking prior to gastric bypass. PMID- 26130134 TI - A histochemical study of the Nras/let-60 activity in filarial nematodes. AB - BACKGROUND: Control and elimination of filarial pathogens is a central focus of major global health efforts directed at parasitic diseases of developing countries. Accomplishment of these goals would be markedly enhanced by the enhanced destruction of the adult stage of filariae. The identification of new, more quantitative biomarkers that correlate with mortality or chemotherapeutic damage to adult filariae, would greatly facilitate, for example, the development of new macrofilaricides. METHODS: An immunocytochemical approach using an antibody against human Nras was used to identify and detect changes in the nematode homolog let-60 that is associated with cell growth and maintenance. Single Onchocerca volvulus nodules were removed from each of 13 patients treated with ivermectin (as part of a community-wide mass drug administration programme), and from each of 13 untreated individuals; these 26 nodules were stained with the anti-Nras antibody. The localization and degree of positivity of Nras/let-60 staining were assessed subjectively and compared between the two groups; the positivity of staining was also quantified, using image analysis, in a subgroup of these nodules. In addition, the specific morphological association between Nras/let-60 and the Wolbachia endosymbiont present in these parasites was also observed in 4 additional filarial species using an anti-Wolbachia surface protein (WSP) antibody under light and confocal microscopy. RESULTS: Nras/let-60 is present in many structures within the adult female worms. A statistically significant decrease in the general staining intensity of Nras/let-60 was observed in adult female O. volvulus treated with ivermectin when compared with parasites from untreated patients. Nras/let-60 staining was frequently observed to be co-localized with WSP in O.volvulus, Brugia malayi, Litomosoides sigmodontis and Dirofilaria immitis. Nras/let60 is also present in Onchocerca ochengi. CONCLUSION: Nras/let-60, as detected by immunocytochemical staining, is decreased in ivermectin-treated adult female O. volvulus relative to untreated control specimens, suggesting a suppressive effect of ivermectin on the overall biochemical activity of these parasites. Co-localization of Nras/let-60 and WSP suggests the possibility that the endosymbiont utilizes this nematode protein as part of a mutualistic relationship. Nras/let60 appears to be a useful biomarker for assessing the health of filariae. PMID- 26130135 TI - Novel naphthochalcone derivative accelerate dermal wound healing through induction of epithelial-mesenchymal transition of keratinocyte. AB - BACKGROUND: Wound healing is an intricate process whereby the skin repairs itself after injury. The epithelial-mesenchymal transition (EMT) is associated with wound healing and tissue regeneration. Naphthochalcone derivatives have various pharmaceutical properties. We investigated the effect of a novel naphthochalcone derivative, 2-(5-(2,4,6-trimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen 1-ol (TDPN), on dermal wound healing in vivo and the migration of keratinocytes in vitro. RESULT: We investigated the effect of TDPN on signaling pathway and epithelial-mesenchymal transition through protein and transcriptional expression. The TDPN treatment accelerated dermal closure about 3 days and remodeling of dermis. We found that treatment with TDPN induced the migration of keratinocytes but not cytotoxicity. TDPN induced the phosphorylation of ERK and AKT. TDPN treated cells showed loss of adherence protein and showed induction of the transcriptional factor Slug, mesenchymal marker, and fibronectin. Moreover, TDPN treatment induced the expression of matrix metalloproteinase-1 (MMP-1), which degrades specific components of the extracellular matrix, thereby providing new substrates that facilitate migration and invasion. MMP expression is considered to be one of the major attributes acquired by cells after EMT. CONCLUSION: We propose that a novel naphthochalcone derivative TDPN is capable of promoting keratinocyte migration via the induction of EMT resulting acceleration of wound closure and matrix remodeling. PMID- 26130137 TI - The Role of Sexual Abuse and Dysfunctional Attitudes in Perceived Stress and Negative Mood in Pregnant Adolescents: An Ecological Momentary Assessment Study. AB - STUDY OBJECTIVE: Latinas have the highest rates of adolescent pregnancy in the United States. Identifying means to improve the well-being of these young women is critical. The current study examined whether a history of child sexual abuse itself a risk factor for adolescent pregnancy-was associated with more perceived stress and negative mood over the course of pregnancy and whether dysfunctional attitudes explained these associations. DESIGN AND SETTING: This mixed methods study involved laboratory-based assessments of perceived stress, sexual abuse history, and dysfunctional attitudes, as well as Ecological Momentary Assessments (EMA) of mood states every 30 minutes during a 24-hour period once during each trimester of pregnancy. PARTICIPANTS: Pregnant adolescents (N = 204, 85% Latina). MAIN OUTCOME MEASURES: EMA mood states and laboratory-based retrospective self reports of perceived stress. RESULTS: One in 4 pregnant adolescents had a history of sexual abuse. Sexually abused adolescents reported greater perceived stress during the first trimester relative to those without, though the groups did not differ on EMA negative mood ratings. Dysfunctional attitudes explained associations between sexual abuse and perceived stress. Sexual abuse was indirectly associated with the intercept and slope of negative mood through dysfunctional attitudes. Findings were circumscribed to sexual abuse and not other types of child abuse. CONCLUSIONS: Identifying sexually abused pregnant adolescents and providing support and cognitive therapy to target dysfunctional beliefs may decrease stress during the first trimester as well as negative affect throughout pregnancy. PMID- 26130136 TI - Gut failure in critical care: old school versus new school. AB - The concept of bacterial translocation and gut-origin sepsis as causes of systemic infectious complications and multiple organ deficiency syndrome in surgical and critically ill patients has been a recurring issue over the last decades attracting the scientific interest. Although gastrointestinal dysfunction seemingly arises frequently in intensive care unit patients, it is usually underdiagnosed or underestimated, because the pathophysiology involved is incompletely understood and its exact clinical relevance still remains controversial with an unknown yet probably adverse impact on the patients' outcome. The purpose of this review is to define gut-origin sepsis and related terms, to describe the mechanisms leading to gut-derived complications, and to illustrate the therapeutic options to prevent or limit these untoward processes. PMID- 26130138 TI - Vesicovaginal Fistula in Adolescent Girls: Incidence and Management. AB - BACKGROUND: The purpose of the study was to analyze the incidence, causes, and management of vesicovaginal fistula (VVF) in adolescent girls. CASES: Three girls of adolescent age were diagnosed with VVF, caused by a vaginal foreign body (ie, an aerosol spray cap). Transvesical reconstruction was performed in 2 cases. After the diagnosis of VVF, the third girl was discharged home with Foley catheter drainage. Three months later, she presented with pregnancy and was lost to follow-up. SUMMARY AND CONCLUSION: Evaluation of unusual urinary symptoms in an adolescent should include vaginal examination and/or imaging. Aerosol spray caps remain the most common vaginal foreign body resulting in VVFs in adolescent girls in Lithuania. Transvesical reconstruction is safe and efficient. PMID- 26130139 TI - Carney complex: an update. AB - Carney complex (CNC) is a rare autosomal dominant syndrome, characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous and other myxomas and multiple endocrine tumors. The disease is caused by inactivating mutations or large deletions of the PRKAR1A gene located at 17q22-24 coding for the regulatory subunit type I alpha of protein kinase A (PKA) gene. Most recently, components of the complex have been associated with defects of other PKA subunits, such as the catalytic subunits PRKACA (adrenal hyperplasia) and PRKACB (pigmented spots, myxomas, pituitary adenomas). In this report, we review CNC, its clinical features, diagnosis, treatment and molecular etiology, including PRKAR1A mutations and the newest on PRKACA and PRKACB defects especially as they pertain to adrenal tumors and Cushing's syndrome. PMID- 26130140 TI - A case of lung adenocarcinoma with a concurrent EGFR mutation and ALK rearrangement: A case report and literature review. AB - The echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion is almost mutually exclusive to epidermal growth factor receptor (EGFR) or K-RAS mutation in non-small cell lung cancer (NSCLC), and it is extremely rare for patients to exhibit both mutations. The present study reported the case of a 71-year-old female diagnosed with adenocarcinoma, exhibiting mutations in EGFR and EML4-ALK. The present study treated this patient with EGFR-TK inhibitors, as the first line therapy, and gefitinib therapy revealed a good response until now. In addition, previously reported cases and associated literature were reviewed. The present study provided a greater understanding of the molecular biology and optimal treatment for patients with NSCLC with >1 driver mutation. PMID- 26130141 TI - Peginterferon plus weight-based ribavirin for treatment-naive hepatitis C virus genotype 2 patients not achieving rapid virologic response: a randomized trial. AB - Hepatitis C virus genotype 2 (HCV-2) slow responders poorly respond to 24 weeks of peginterferon (Peg-IFN) plus ribavirin (RBV). We evaluated the efficacy of extended 48-week regimen and the role of interleukin-28B (IL-28B) genotype in this clinical setting. Treatment-naive HCV-2 patients not achieving rapid virologic response (RVR) by Peg-IFN alfa-2a 180 MUg/week plus weight-based RBV (1,000-1,200 mg/day, cutoff body weight of 75 kg) were randomly assigned to receive a total duration of 48 (n = 94) or 24 (n = 93) weeks of therapy. The primary endpoint was sustained virologic response (SVR). Baseline patient characteristics to predict SVR were analyzed. Patients receiving 48 weeks of treatment had a greater SVR rate than those receiving 24 weeks of treatment (70.2% versus 46.2%, P = 0.001). Compared to patients treated for 24 weeks, the SVR rate in those treated for 48 weeks increased by 10.9% [95% CI: -5.9% to 27.7%] and 65.6% [95% CI: 44.5% to 86.7%] if they had IL-28B rs8099917 TT genotype, and GT/GG genotype, respectively (interaction P = 0.002). In conclusion, 48-week treatment with Peg-IFN plus weight-based RBV provides a greater SVR rate than 24-week treatment in treatment-naive HCV-2 patients with unfavorable IL-28B genotypes who fail to achieve RVR. PMID- 26130142 TI - Silencing or inhibition of endoplasmic reticulum aminopeptidase 1 (ERAP1) suppresses free heavy chain expression and Th17 responses in ankylosing spondylitis. AB - OBJECTIVE: Human leucocyte antigen (HLA)-B27 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly associated with ankylosing spondylitis (AS). ERAP1 is a key aminopeptidase in HLA class I presentation and can potentially alter surface expression of HLA-B27 free heavy chains (FHCs). We studied the effects of ERAP1 silencing/inhibition/variations on HLA-B27 FHC expression and Th17 responses in AS. METHODS: Flow cytometry was used to measure surface expression of HLA class I in peripheral blood mononuclear cells (PBMCs) from patients with AS carrying different ERAP1 genotypes (rs2287987, rs30187 and rs27044) and in ERAP1-silenced/inhibited/mutated HLA-B27-expressing antigen presenting cells (APCs). ERAP1-silenced/inhibited APCs were cocultured with KIR3DL2CD3epsilon-reporter cells or AS CD4+ T cells. Th17 responses of AS CD4+ T cells were measured by interleukin (IL)-17A ELISA and Th17 intracellular cytokine staining. FHC cell surface expression and Th17 responses were also measured in AS PBMCs following ERAP1 inhibition. RESULTS: The AS-protective ERAP1 variants, K528R and Q730E, were associated with reduced surface FHC expression by monocytes from patients with AS and HLA-B27-expressing APCs. ERAP1 silencing or inhibition in APCs downregulated HLA-B27 FHC surface expression, reduced IL-2 production by KIR3DL2CD3epsilon-reporter cells and suppressed the Th17 expansion and IL-17A secretion by AS CD4+ T cells. ERAP1 inhibition of AS PBMCs reduced HLA class I FHC surface expression by monocytes and B cells, and suppressed Th17 expansion. CONCLUSIONS: ERAP1 activity determines surface expression of HLA-B27 FHCs and potentially promotes Th17 responses in AS through binding of HLA-B27 FHCs to KIR3DL2. Our data suggest that ERAP1 inhibition has potential for AS treatment. PMID- 26130143 TI - Solid-state fermentation of whole oats to yield a synbiotic food rich in lactic acid bacteria and prebiotics. AB - This study developed a synbiotic food through the fermentation of whole oat flour with Lactobacillus plantarum TK9 and Bifidobacterium animalis subsp. lactis V9. The physicochemical properties, changes in ingredients and peptide molecular weight distributions were determined during the whole oat fermentation. The highest viable counts of the fermented oats were 2.85 * 10(9) CFU g(-1) (L. plantarum TK9) and 3.17 * 10(8) CFU g(-1) (Bif. animalis subsp. lactis V9), with the titratable acidity increased to 10.01 and 8.40 mL at the end of the fermentation. By comparing the nutrition compositions between the fermented and non-fermented oat flour, we found that there was almost no change in the soluble dietary fiber and beta-glucan content. However, the amounts of free amino nitrogen increased from 110.84 to 154.62 mg per 100 g (L. plantarum TK9) and 82.16 to 104.83 mg per 100 g (Bif. animalis subsp. lactis V9). The levels of oat peptides with molecular weights less than 6000 Da increased by 4.4 and 5.96%, respectively. The results suggest that the fermented whole oat flour has good potential for application in the production of a novel synbiotic food rich in lactic acid bacteria and beta-glucan prebiotics. PMID- 26130144 TI - Oral non-steroidal anti-inflammatory drugs versus other oral analgesic agents for acute soft tissue injury. AB - BACKGROUND: Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti inflammatory drugs (NSAIDs) are often recommended. OBJECTIVES: To assess the effects (benefits and harms) of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (12 September 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014 Issue 8), MEDLINE (1966 to September 2014), EMBASE (1980 to September 2014), CINAHL (1937 to November 2012), AMED (1985 to November 2012), International Pharmaceutical Abstracts (1970 to November 2012), PEDro (1929 to November 2012), and SPORTDiscus (1985 to November 2012), plus internet search engines, trial registries and other databases. We also searched reference lists of relevant articles and contacted authors of retrieved studies and pharmaceutical companies to obtain relevant unpublished data. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials involving people with acute soft tissue injury (sprain, strain or contusion of a joint, ligament, tendon or muscle occurring up to 48 hours prior to inclusion in the study) and comparing oral NSAID versus paracetamol (acetaminophen), opioid, paracetamol plus opioid, or complementary and alternative medicine. The outcomes were pain, swelling, function, adverse effects and early re-injury. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed studies for eligibility, extracted data and assessed risk of bias. We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. MAIN RESULTS: We included 16 trials, with a total of 2144 participants. Two studies included children only. The other 14 studies included predominantly young adults, of whom over 60% were male. Seven studies recruited people with ankle sprains only. Most studies were at low or unclear risk of bias; however, two were at high risk of selection bias, three were at high risk of bias from lack of blinding, one was at high risk of bias due to incomplete outcome data, and four were at high risk of selective outcome reporting bias. The evidence was usually either low quality or very low quality, reflecting study limitations, indirectness such from as suboptimal dosing of single comparators, imprecision, or one or more of these. Thus we are either uncertain or very uncertain of the estimates.Nine studies, involving 991 participants, compared NSAIDs with paracetamol. While tending to favour paracetamol, there was a lack of clinically important differences between the two groups in pain at less than 24 hours (377 participants, 4 studies; moderate-quality evidence), at days 1 to 3 (431 participants, 4 studies; low quality), and at day 7 or over (467 participants, 4 studies; low quality). A similar lack of difference between the two groups applied to swelling at day 3 (86 participants, 1 study; very low quality) and at day 7 or over (77 participants, 1 study; low quality). There was little difference between the two groups in return to function at day 7 or over (316 participants, 3 studies; very low quality): based on an assumed recovery of function of 804 per 1000 participants in the paracetamol group, 8 fewer per 1000 recovered in the NSAID group (95% confidence interval (CI) 80 fewer to 73 more). There was low-quality evidence of a lower risk of gastrointestinal adverse events in the paracetamol group: based on an assumed risk of gastrointestinal adverse events of 16 per 1000 participants in the paracetamol group, 13 more participants per 1000 had a gastrointestinal adverse event in the NSAID group (95% CI 0 to 35 more).Four studies, involving 958 participants, compared NSAIDs with opioids. Since a study of a selective COX-2 inhibitor NSAID (valdecoxib) that was subsequently withdrawn from the market dominates the evidence for this comparison (706 participants included in the analyses for pain, function and gastrointestinal adverse events), the applicability of these results is in doubt and we give only a brief summary. There was low quality evidence for a lack of clinically important differences between the two groups regarding pain at less than 24 hours, at days 4 to 6, and at day 7. Evidence from single studies showed a similar lack of difference between the two groups for swelling at day 3 (68 participants) and day 10 (84 participants). Return to function at day 7 or over favoured the NSAID group (low-quality), and there were fewer gastrointestinal adverse events in the selective COX-2 inhibitor NSAID group (very low quality).Four studies, involving 240 participants, compared NSAIDs with the combination of paracetamol and an opioid. The applicability of findings from these studies is partly in question because the dextropropoxyphene combination analgesic agents used are no longer in general use. While the point estimates favoured NSAID, the very low-quality evidence did not show a difference between the two interventions in the numbers with little or no pain at day 1 (51 participants, 1 study), day 3 (149 participants, 2 studies), or day 7 (138 participants, 2 studies). Very low-quality evidence showed a similar lack of difference between the two groups applied to swelling at day 3 (reported in two studies) and at day 7 (reported in two studies), in return to function at day 7 (89 participants, 1 study), and in gastrointestinal adverse events (141 participants, 3 studies).No studies compared NSAIDs with complementary and alternative medicines, and no study reported re-injury rates. AUTHORS' CONCLUSIONS: There is generally low- or very low-quality but consistent evidence of no clinically important difference in analgesic efficacy between NSAIDs and other oral analgesics. There is low-quality evidence of more gastrointestinal adverse effects with non-selective NSAID compared with paracetamol. There is low- or very low-quality evidence of better function and fewer adverse events with NSAIDs compared with opioid-containing analgesics; however, one study dominated this evidence using a now unavailable COX-2 selective NSAID and is of uncertain applicability. Further research is required to determine whether there is any difference in return to function or adverse effects between both non-selective and COX-2 selective NSAIDs versus paracetamol. PMID- 26130145 TI - Mild encephalitis/encephalopathy with a reversible splenial lesion: five cases and a literature review. AB - The aim of this study was to explore the clinical characteristics and etiology of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in China by retrospectively analyzing five MERS cases from the Jiangsu Provincial Hospital within a total of 27 reported MERS cases from available Chinese literature. Most of the 27 cases originated near the eastern and southern parts of China. Ages for 23 MERS cases were under 30 years and the female-to-male ratio was 1:1.25. The major causes of MERS included infection, antiepileptic drug withdrawal, high-altitude cerebral edema, and cesarean section (C-section). Hyponatremia was also observed in 10 MERS cases. All patients had a complete recovery within a month. Steroids and IVIG were the most commonly used therapy for MERS, but their efficiency remained questionable. PMID- 26130146 TI - Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients. AB - The presence of cerebrospinal fluid oligoclonal bands (CSF-OCB) in Caucasian patients with multiple sclerosis (MS) is supportive of diagnosis, though the relation with patients' clinical and specifically cognitive features has never been established or thoroughly examined. Thus, we investigated the clinical and for the first time the cognitive profile of MS patients in relation to CSF-OCB. We studied 108 patients with and without OCB and recorded demographic characteristics and detailed clinical data. A comprehensive neuropsychological battery covering different cognitive domains (attention/processing speed, memory, perception/constructions, reasoning, executive functions) was administered to MS patients and 142 demographically related healthy controls (HC). We did not find any significant differences between patients with and without OCB on demographic and clinical parameters (p > 0.05), including subtype and brain neuroimaging findings. Results revealed significantly higher cognitive scores in HC compared to both OCB subgroups, with more widespread cognitive changes in patients with OCB. Analysis between OCB subgroups showed significantly worse performance in patients with OCB on visual memory (Rey's complex figure test-recall; p = 0.006). Concluding, the presence of CSF-OCB in our MS patients tends to be related to more widespread cognitive changes, specifically worse visual memory. Future longitudinal studies in different populations are warranted to better clarify the clinical and cognitive characteristics related to CSF-OCB which could serve as early biomarker in disease monitoring. PMID- 26130147 TI - Bilateral episcleritis followed by right optic perineuritis with severe visual loss: a case report. PMID- 26130148 TI - mTORC2 Balances AKT Activation and eIF2alpha Serine 51 Phosphorylation to Promote Survival under Stress. AB - The mTOR nucleates two complexes, namely mTOR complex 1 and 2 (mTORC1 and mTORC2), which are implicated in cell growth, survival, metabolism, and cancer. Phosphorylation of the alpha-subunit of translation initiation factor eIF2 at serine 51 (eIF2alphaS51P) is a key event of mRNA translation initiation and a master regulator of cell fate during cellular stress. Recent studies have implicated mTOR signaling in the stress response, but its connection to eIF2alphaS51P has remained unclear. Herein, we report that genetic as well as catalytic inhibition of mTORC2 induces eIF2alphaS51P. On the other hand, the allosteric inhibitor rapamycin induces eIF2alphaS51P through pathways that are independent of mTORC1 inactivation. Increased eIF2alphaS51P by impaired mTORC2 depends on the inactivation of AKT, which primes the activation of the endoplasmic reticulum (ER)-resident kinase PERK/PEK. The biologic function of eIF2alphaS51P was characterized in tuberous sclerosis complex (TSC)-mutant cells, which are defective in mTORC2 and AKT activity. TSC-mutant cells exhibit increased PERK activity, which is downregulated by the reconstitution of the cells with an activated form of AKT1. Also, TSC-mutant cells are increasingly susceptible to ER stress, which is reversed by AKT1 reconstitution. The susceptibility of TSC-mutant cells to ER stress is further enhanced by the pharmacologic inhibition of PERK or genetic inactivation of eIF2alphaS51P. Thus, the PERK/eIF2alphaS51P arm is an important compensatory prosurvival mechanism, which substitutes for the loss of AKT under ER stress. IMPLICATIONS: A novel mechanistic link between mTOR function and protein synthesis is identified in TSC null tumor cells under stress and reveals potential for the development of antitumor treatments with stress-inducing chemotherapeutics. PMID- 26130149 TI - Accelerating Science-to-Practice for Early Psychosis. PMID- 26130151 TI - "Boarding" Psychiatric Patients in Emergency Rooms: One Court Says "No More". AB - "Boarding" involuntary psychiatric patients in medical emergency rooms is common in many parts of the United States. The practice, driven by a shortage of alternative resources, including limited inpatient capacity, can result in patients' being held for days without treatment or a hospital room, often in busy corridors or treatment rooms. A recent challenge to this practice led the Washington Supreme Court to declare it illegal and resulted in the appropriation of substantial funding to create new psychiatric beds. Centralized psychiatric crisis services, with appropriate payment models, may offer another approach to reducing the need for holding patients awaiting inpatient admission. PMID- 26130152 TI - Paying for Early Interventions in Psychoses: A Three-Part Model. AB - Widespread dissemination of early interventions for psychosis, such as the intervention offered in the RAISE study (Recovery After an Initial Schizophrenia Episode), requires a funding mechanism that is both compatible with approaches already used by payers and generates incentives for providers that promote the desired behaviors. The authors propose a funding model with three components: a prospective per-case payment made conditional on patient engagement in treatment, a per-service component to cover the costs of clinical services, and an outcome based component conditional on achieving measurable outcome milestones. The authors describe the components and how such a payment mechanism might be implemented. PMID- 26130153 TI - The Three-Part Model to Pay for Early Interventions for Psychoses. PMID- 26130154 TI - Technology Access and Use Among Young Adults With a First Episode of Psychosis. PMID- 26130156 TI - Quality of life and side effects in patients with actinic keratosis treated with ingenol mebutate: a pilot study. AB - INTRODUCTION: Actinic keratosis (AK) lesions are in situ squamous cell carcinoma. These lesions have a low risk of progressing to invasive disease but significant impact on patients' quality of life (QoL). The aim of this study was to assess QoL and side effects in patients with AK receiving treatment with ingenol mebutate. MATERIAL AND METHODS: This was a prospective, non-randomized pilot study carried out in Spain. The target population was adults with a clinical diagnosis of AK affecting any part of the body. Outcomes were assessed on the basis of a QoL questionnaire (Skindex-29), local skin response, the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), and clinical response. RESULTS: A total of 19 patients were studied. Most of the participants were men (89.5%) and mean age was 76.2 years. After treatment with ingenol mebutate, significant improvement was observed in the Skindex-29 subscales relating to symptom severity (P=.041), the patients' emotional state (P=.026), and in the overall score (P=.014). Erythema, crusting, and flaking or scaling were the local skin responses with highest median score (2.0 in all 3 cases). Imiquimod 5% and ingenol mebutate achieved higher median scores for effectiveness and global satisfaction than any other previous treatments (as measured by TSQM 1.4). In the patients' assessment of convenience, ingenol mebutate had a higher median score than previous treatments. Over half of the patients (52.6%) had an improvement of at least 75% at month 3. CONCLUSIONS: QoL in patients with AK improves after treatment with ingenol mebutate. The presence of side effects did not affect QoL or patient satisfaction with treatment. PMID- 26130157 TI - TRPV3 Channel Negatively Regulates Cell Cycle Progression and Safeguards the Pluripotency of Embryonic Stem Cells. AB - Embryonic stem cells (ESCs) have tremendous potential for research and future therapeutic purposes. However, the calcium handling mechanism in ESCs is not fully elucidated. Aims of this study are (1) to investigate if transient receptor potential vanilloid-3 (TRPV3) channels are present in mouse ESCs (mESCs) and their subcellular localization; (2) to investigate the role of TRPV3 in maintaining the characteristics of mESCs. Western blot and immunocytochemistry showed that TRPV3 was present at the endoplasmic reticulum (ER) of mESCs. Calcium imaging showed that, in the absence of extracellular calcium, TRPV3 activators camphor and 6-tert-butyl-m-cresol increased the cytosolic calcium. However, depleting the ER store in advance of activator addition abolished the calcium increase, suggesting that TRPV3 released calcium from the ER. To dissect the functional role of TRPV3, TRPV3 was activated and mESC proliferation was measured by trypan blue exclusion and MTT assays. The results showed that TRPV3 activation led to a decrease in mESC proliferation. Cell cycle analysis revealed that TRPV3 activation increased the percentage of cells in G2 /M phase; consistently, Western blot also revealed a concomitant increase in the expression of inactive form of cyclin-dependent kinase 1, suggesting that TRPV3 activation arrested mESCs at G2 /M phase. TRPV3 activation did not alter the expression of pluripotency markers Oct-4, Klf4 and c-Myc, suggesting that the pluripotency was preserved. Our study is the first study to show the presence of TRPV3 at ER. Our study also reveals the novel role of TRPV3 in controlling the cell cycle and preserving the pluripotency of ESCs. PMID- 26130158 TI - Re-shaping graphene hydrogels for effectively enhancing actuation responses. AB - The development of actuation-enabled materials is important for smart devices and systems. Among them, graphene with outstanding electric, thermal, and mechanical properties holds great promise as a new type of stimuli-responsive material. In this study, we developed a re-shaping strategy to construct structure-controlled graphene hydrogels for highly enhanced actuation responses. Actuators based on the re-shaped graphene hydrogel showed a much higher actuation response than that of the common graphene counterparts. On the other hand, once composited with a conducting polymer (e.g., polypyrrole), the re-shaped hybrid actuator exhibits excellent actuation behavior in response to electrochemical potential variation. Even under stimulation at a voltage as low as 0.8 V, actuators based on the re shaped graphene-polypyrrole composite hydrogel exhibit a maximum strain response of up to 13.5%, which is the highest value reported to date for graphene-based materials. PMID- 26130159 TI - Energy landscape scheme for an intuitive understanding of complex domain dynamics in ferroelectric thin films. AB - Fundamental understanding of domain dynamics in ferroic materials has been a longstanding issue because of its relevance to many systems and to the design of nanoscale domain-wall devices. Despite many theoretical and experimental studies, a full understanding of domain dynamics still remains incomplete, partly due to complex interactions between domain-walls and disorder. We report domain-shape preserving deterministic domain-wall motion, which directly confirms microscopic return point memory, by observing domain-wall breathing motion in ferroelectric BiFeO3 thin film using stroboscopic piezoresponse force microscopy. Spatial energy landscape that provides new insights into domain dynamics is also mapped based on the breathing motion of domain walls. The evolution of complex domain structure can be understood by the process of occupying the lowest available energy states of polarization in the energy landscape which is determined by defect-induced internal fields. Our result highlights a pathway for the novel design of ferroelectric domain-wall devices through the engineering of energy landscape using defect-induced internal fields such as flexoelectric fields. PMID- 26130160 TI - Community-based interventions for improving maternal health and for reducing maternal health inequalities in high-income countries: a systematic map of research. AB - BACKGROUND: This review is part of a European Commission project, MASCOT, aimed at reducing maternal and child health inequalities. The purpose was to identify and describe the literature on community-based interventions on maternal health in high-income countries (HIC) and conceptually map the literature according to country focus, topics addressed, nature of the intervention and the intervention provider, and interventions designed to address inequalities in maternal health. METHODS: The research protocol for this review was based on a low-income country (LMIC) systematic review protocol within the MASCOT Project. We searched PubMED and CINAHL databases for literature published between January 2000 and April 2013. OECD countries were used to determine the HIC and different terms were used to refer to community based interventions, defined as those "delivered in community settings or any activities occurring outside of health facilities". RESULTS: 119 publications were selected for inclusion in this mapping study. 95 (80%) were Randomised Control Trials (RCTs) and 24 (20%) were systematic reviews (SRs). We categorised the study topics according to the main interventions covered: breastfeeding assistance and promotion, preventing and treating post natal depression, interventions to support and build capacity around parenting and child care, antenatal interventions preparing women for birth, postnatal planning of future births and control trials around changing maternal behaviours. The home was used as the most common setting to implement these interventions and health professionals accounted for the largest group of intervention providers. CONCLUSIONS: This review maps and brings knowledge on the type of studies and topics being addressed in community based interventions around maternal health in HICs. It opens the opportunity for further studies on interventions' effectiveness and knowledge transfer to LMICs settings. PMID- 26130161 TI - Synthesis of Amathaspiramides by Aminocyanation of Enoates. AB - Concise routes for the total and formal syntheses of the amathaspiramides were developed through a formal [3+2] cycloaddition between lithium(trimethylsilyl)diazomethane and alpha,beta-unsaturated esters. The effectiveness of this new cycloaddition for the construction of Delta(2) pyrazolines containing a alpha-tert-alkylamino carbon center and subsequent facile protonolytic N-N bond cleavage allows the synthesis of a key intermediate of the amathaspiramides and other alpha,alpha-disubstituted amino acid derivatives. PMID- 26130162 TI - Sleep: Don't forget. PMID- 26130163 TI - Neuroendocrinology: More nutritious than delicious. PMID- 26130164 TI - Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date. AB - The longest survival of a non-human primate with a life-supporting kidney graft to date has been 90 days, although graft survival > 30 days has been unusual. A baboon received a kidney graft from an alpha-1,3-galactosyltransferase gene knockout pig transgenic for two human complement-regulatory proteins and three human coagulation-regulatory proteins (although only one was expressed in the kidney). Immunosuppressive therapy was with ATG+anti-CD20mAb (induction) and anti CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-alpha and anti-IL-6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6 to 1.6 mg/dl) until termination. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response. Death was from septic shock (Myroides spp). Histology of a biopsy on day 103 was normal, but by day 136, the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory agents prevented immune injury and a protein-losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality. PMID- 26130165 TI - Characterization of Osmotolerant Yeasts and Yeast-Like Molds from Apple Orchards and Apple Juice Processing Plants in China and Investigation of Their Spoilage Potential. AB - Yeasts and yeast-like fungal isolates were recovered from apple orchards and apple juice processing plants located in the Shaanxi province of China. The strains were evaluated for osmotolerance by growing them in 50% (w/v) glucose. Of the strains tested, 66 were positive for osmotolerance and were subsequently identified by 26S or 5.8S-ITS ribosomal RNA (rRNA) gene sequencing. Physiological tests and RAPD-PCR analysis were performed to reveal the polymorphism of isolates belonging to the same species. Further, the spoilage potential of the 66 isolates was determining by evaluating their growth in 50% to 70% (w/v) glucose and measuring gas generation in 50% (w/v) glucose. Thirteen osmotolerant isolates representing 9 species were obtained from 10 apple orchards and 53 target isolates representing 19 species were recovered from 2 apple juice processing plants. In total, members of 14 genera and 23 species of osmotolerant isolates including yeast-like molds were recovered from all sources. The commonly recovered osmotolerant isolates belonged to Kluyveromyces marxianus, Hanseniaspora uvarum, Saccharomyces cerevisiae, Zygosaccharomyces rouxii, Candida tropicalis, and Pichia kudriavzevii. The polymorphism of isolates belonging to the same species was limited to 1 to 3 biotypes. The majority of species were capable of growing within a range of glucose concentration, similar to sugar concentrations found in apple juice products with a lag phase from 96 to 192 h. Overall, Z. rouxii was particularly the most tolerant to high glucose concentration with the shortest lag phase of 48 h in 70% (w/v) glucose and the fastest gas generation rate in 50% (w/v) glucose. PMID- 26130166 TI - Quantitation of the Regional Lymph Node Metastatic Burden and Prognosis in Malignant Mammary Tumors of Dogs. AB - BACKGROUND: As in women, regional lymph node status impacts survival in dogs with malignant mammary tumors. However, few studies have evaluated regional lymph node metastases in dogs with malignant mammary gland tumors. OBJECTIVES: To estimate overall survival based on the assessments of the lymph node status and the morphologic and morphometric features in female dogs with malignant mammary gland tumors. MATERIALS AND METHODS: In total, 178 lymph nodes from 97 female dogs were assessed and reviewed, and after confirmation by immunohistochemistry (IHC), 161 lymph nodes were selected for analysis of metastases. Animals were considered metastasis-free (negative lymph nodes) only after IHC analysis for cytokeratin AE1/AE3. The number of positive lymph nodes, the number of metastatic foci, the maximum diameter and the area of metastasis were analyzed, and estimates of overall survival were made. RESULTS: Dogs with metastasis had lower mean survival than those with metastasis-free regional lymph nodes, showing a direct relationship between the number of affected lymph nodes and shorter survival. However, histologic analysis of the lymph nodes identified lower survival rates in animals with macrometastases and isolated tumor cells, areas of metastasis >20.11 mm2, and metastatic diameters >7.32 mm. CONCLUSION: The identification of >=1 lymph nodes positive for metastasis and morphometric characterization of lymphatic metastases indicate the prognostic relevance of lymph nodes status in dogs with mammary tumors. PMID- 26130168 TI - Amyloid PET in European and North American cohorts; and exploring age as a limit to clinical use of amyloid imaging. AB - PURPOSE: Several radiotracers that bind to fibrillar amyloid-beta in the brain have been developed and used in various patient cohorts. This study aimed to investigate the comparability of two amyloid positron emission tomography (PET) tracers as well as examine how age affects the discriminative properties of amyloid PET imaging. METHODS: Fifty-one healthy controls (HCs), 72 patients with mild cognitive impairment (MCI) and 90 patients with Alzheimer's disease (AD) from a European cohort were scanned with [11C]Pittsburgh compound-B (PIB) and compared with an age-, sex- and disease severity-matched population of 51 HC, 72 MCI and 84 AD patients from a North American cohort who were scanned with [18F]Florbetapir. An additional North American population of 246 HC, 342 MCI and 138 AD patients with a Florbetapir scan was split by age (55-75 vs 76-93 y) into groups matched for gender and disease severity. PET template-based analyses were used to quantify regional tracer uptake. RESULTS: The mean regional uptake patterns were similar and strong correlations were found between the two tracers across the regions of interest in HC (rho = 0.671, p = 0.02), amyloid-positive MCI (rho = 0.902, p < 0.001) and AD patients (rho = 0.853, p < 0.001). The application of the Florbetapir cut-off point resulted in a higher proportion of amyloid-positive HC and a lower proportion of amyloid-positive AD patients in the older group (28 and 30 %, respectively) than in the younger group (19 and 20 %, respectively). CONCLUSIONS: These results illustrate the comparability of Florbetapir and PIB in unrelated but matched patient populations. The role of amyloid PET imaging becomes increasingly important with increasing age in the diagnostic assessment of clinically impaired patients. PMID- 26130169 TI - Heavy metal enrichment characteristics in ash of municipal solid waste combustion in CO2/O2 atmosphere. AB - This paper investigated the behavior of six heavy metals (Cd, Pb, Cu, Cr, Ni and Zn) in the bottom ashes of recycled polyvinyl chloride pellets (PVC), wood sawdust (WS) and paper mixture (PM), representing the common components of municipal solid waste (MSW), obtained during combustion in CO2/O2 atmosphere in a lab-scale electrically heated tube furnace. Replacement of N2 by CO2 did not obviously change the shape of relative enrichment factor (RE) curves and subsequent order of heavy metals, but increased enrichment of these heavy metals in bottom ashes of WS, PM and PVC. The increment of O2 concentration in CO2/O2 atmosphere further increased RE values. It was only when the temperature was higher than or equal to 700 degrees C that the increment of the combustion temperature reduced the RE values of heavy metals. The effect of temperature on heavy metals evaporation was the most pronounced for the medium volatile metal Pb, and the least for the low volatiles Cr and Ni. The effect of temperature was more pronounced for PVC ash than for WS and PM ashes. This paper contributes to the control of heavy metals during MSW incineration and management of MSW oxy fuel residues. PMID- 26130170 TI - Temporal trends in the levels of metals, PCDD/Fs and PCBs in the vicinity of a municipal solid waste incinerator. Preliminary assessment of human health risks. AB - The concentrations of PCDD/Fs, PCBs, and metals were determined in soil and air samples collected near a municipal solid waste incinerator (MSWI) located in Mataro (Catalonia, Spain), being the health risks for the population living in the vicinity of the facility subsequently assessed. We also established the temporal trends with respect to previous surveys performed in the same zone. In general terms, the highest environmental levels of the pollutants were found in the city of Mataro and were independent on the distance to the MSWI. Soil levels of metals did not show temporal variations between the current and previous campaigns. However, the concentrations of metals in air samples collected in 2011 and 2013, were lower than those found in our 2008 survey. Regarding PCDD/Fs and PCBs, no differences were noted between the levels of the current survey and those corresponding to 2008. Anyhow, the concentrations of metals, PCDD/Fs, and PCBs in soils and air did not exceed the reference values established by regulatory organizations, being also in the low range of other similar studies recently reported. Finally, the human non-carcinogenic and carcinogenic risks due to exposure to metals, PCDD/Fs, and PCBs, were, for the population living in the neighborhood of the MSWI, considered as acceptable according to international standards. PMID- 26130171 TI - Food waste generation and industrial uses: A review. AB - Food waste is made up of materials intended for human consumption that are subsequently discharged, lost, degraded or contaminated. The problem of food waste is currently on an increase, involving all sectors of waste management from collection to disposal; the identifying of sustainable solutions extends to all contributors to the food supply chains, agricultural and industrial sectors, as well as retailers and final consumers. A series of solutions may be implemented in the appropriate management of food waste, and prioritised in a similar way to waste management hierarchy. The most sought-after solutions are represented by avoidance and donation of edible fractions to social services. Food waste is also employed in industrial processes for the production of biofuels or biopolymers. Further steps foresee the recovery of nutrients and fixation of carbon by composting. Final and less desirable options are incineration and landfilling. A considerable amount of research has been carried out on food waste with a view to the recovery of energy or related products. The present review aims to provide an overview of current debate on food waste definitions, generation and reduction strategies, and conversion technologies emerging from the biorefinery concept. PMID- 26130172 TI - Cooper pair splitting in parallel quantum dot Josephson junctions. AB - Devices to generate on-demand non-local spin entangled electron pairs have potential application as solid-state analogues of the entangled photon sources used in quantum optics. Recently, Andreev entanglers that use two quantum dots as filters to adiabatically split and separate the quasi-particles of Cooper pairs have shown efficient splitting through measurements of the transport charge but the spin entanglement has not been directly confirmed. Here we report measurements on parallel quantum dot Josephson junction devices allowing a Josephson current to flow due to the adiabatic splitting and recombination of the Cooper pair between the dots. The evidence for this non-local transport is confirmed through study of the non-dissipative supercurrent while tuning independently the dots with local electrical gates. As the Josephson current arises only from processes that maintain the coherence, we can confirm that a current flows from the spatially separated entangled pair. PMID- 26130173 TI - The value and availability of forensic anthropological consultation in medicolegal death investigations. PMID- 26130174 TI - Optical clearing of the dura mater using glycerol: a reversible process to aid the post-mortem investigation of infant head injury. AB - PURPOSE: In cases of suspected abusive head trauma, a thorough and systematic study of the cranium and its contents is essential, preferably using the best available methods for observing the brain and its coverings. Building upon recent developments in skull bone removal techniques in infant autopsies, we have assessed the use of two optical clearing agents (OCAs), glycerol and mannitol, on pediatric dura mater in an attempt to increase the transparency of this tissue and thereby enhance the post-mortem assessment of infant head injuries, particularly subdural hematomas. METHODS: Extracorporeal testing revealed glycerol to be the more effective OCA. Therefore, in situ investigations were commenced using glycerol during 33 pediatric post-mortem examinations. RESULTS: An increase in the transparency of the dura was observed in 32 of the 33 cases, within 1 min of application of the OCA. In a 2 year old with cerebral palsy, only partial optical clearance of the dura was seen, most likely due to a significantly atrophic brain, prominent gelatinous leptomeninges, and abnormally thickened dura. This technique allowed for detection of minimal amounts of subdural bleeding over the convexities, before dissection of the dura, avoiding post-mortem blood spillage from artifactually disrupted bridging veins. Optical clearing of the dura aided in the evaluation of patterns of subdural hemorrhage in three cases of non-accidental head injury, three cases of peri-natal head injury and one case of overlaying, apparently resulting in minor crush injury to the head. CONCLUSIONS: We have demonstrated that glycerol is an effective and easy-to-use OCA to effect the readily reversible optical clearing of human infant calvarial dura at autopsy. PMID- 26130175 TI - ABO, alemtuzumab and allogeneic transplantation. PMID- 26130176 TI - Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies. PMID- 26130177 TI - Standardized Technique of Laparoscopic Adjustable Gastric Banded Plication with 4 Year Results. AB - BACKGROUND: No bariatric procedure is perfect, and a plethora of such procedures itself is a proof for the same. Laparoscopic adjustable gastric banding has a high safety profile, but also a high rate of re-operation has been reported (Schouten, Wiryasaputra, van Dielen et al. Obes Surg 20(12):1617-26, 2010). Laparoscopic sleeve gastrectomy (LSG) is becoming popular, but has its own set of complications and is irreversible. We introduced laparoscopic adjustable gastric banded plication (LAGBP) in 2009 (Huang, Lo, Shabbir et al. Surg Obes Relat Dis 8(1):41-5, 2012) In a case matched comparative study with LSG, LAGBP showed similar results at 2 years in terms of weight loss, comorbidity resolution, and complications. (Huang, Chhabra, Goel et al. Obes Surg 23(8):1319-23, 2013). Several authors have reported variations in their technique, bougie size, and suture material used to perform plication. (Ramos, Galvao Neto, Galvao et al. Obes Surg 20(7):913-8, 2010, (Mui, Lee, Lam et al. Obes Surg 23(2): 179-83, 2013, Brethauer, Harris, Kroh et al. Surg Obes Relat Dis 7(1):15-22, 2011) Our initial technique of placing the band first and then plicating the stomach resulted in higher incidence of gastric fundus herniation compared to that reported in a systematic review (Abdelbaki, Huang, Ramos et al. Obes Surg 22(10):1633-9, 2012). After the first 65 cases, we reversed the order by performing the gastric plication first which ensures proper plication of the fundus and a more uniformly placed plication line. This technique has become our standard, and the same is described in this video in a stepwise fashion. MATERIALS AND METHODS: We performed LAGBP in 202 cases over the last 4 years and recorded the findings. Our standardized technique is shown in this video. The T-suspension technique was used for liver retraction. (Zachariah, Tai, Chang et al. J Laparoendosc Adv Surg Tech A 23(4):311-5, 2013) Gastric plication formula is shown in Fig. 1. Fig. 1 Gastric plication formula RESULTS: Two hundred two (69 male, 133 female) patients in over the last 4 years underwent LAGBP. Follow-up at 1 year was 168 patients, and 56 patients reached 4-year follow-up. Age was 16-60 years (mean = 31.1). Mean BMI was 39.5 +/- 3.18 and body weight 110 kg +/- 19.4. Mean operative time was 104 min +/- 39 and length of hospital stay after surgery 2.1 +/- 2.3 days. No mortality was recorded. Excess weight loss at 1 year was 57.84 % and at four years 68 %. CONCLUSION: LAGBP has been proven to be an effective bariatric procedure in the midterm results. Standardization with plication first and then placement of the band could be important to achieve best outcomes. PMID- 26130178 TI - A Challenging Misleading Diagnosis in a Patient with Suspicion of Gastric Banding Slippage and Strangulation: Diagnosis and Laparoscopic Treatment. AB - A 51-year-old female (height 160 cm, weight 89 kg, BMI 34.8) presented at the emergency department complaining of sudden onset of sharp abdominal pain in the epigastrium, colicky in nature, dysphagia, nausea, and repeated retching with non productive vomiting. She has had an adjustable gastric banding implanted laparoscopically 11 years earlier. Since then, she reported to have had only a moderate weight loss (initial BMI 44), although she was closely followed up and the reservoir properly filled by her obesity surgeon. A gastrografin was performed and showed no clear signs of slippage of the gastric band nor of gastric strangulation/ischemia. Nonetheless, the passage of the contrast through esophagogastric junction was slightly slow and restricted suggesting a moderate stenosis from the band. Two cubic centimeters of saline were aspirated from the reservoir to loosen the gastric band. However, on the following minutes, no significant relief of the sharp pain was observed. NSAIDS and morphine were repeatedly given without significant pain relief, and after a few hours, the pain was more intense and diffused to the upper abdomen. I.V. contract CT scan showed a large amount of free fluid, with severe small bowel distension and suspected volvulus and a transition point at the port site of the reservoir, suggesting a strangulated incisional hernia on this site and/or strangulating band adhesion. Urgent surgery was planned, and a laparoscopic approach was chosen. A large amount of free bloody fluid was found, and a long segment of small bowel was twisted around a strangulating band adhesion on the port site of the reservoir, incarcerated within an incisional hernia on the same port site. The strangulating band was cut, and the strangulated bowel was released. Gradual reversion of bowel ischemia was observed, and the gastric banding was removed according to the patient's preoperative request. PMID- 26130179 TI - The Effect of Ventilation Strategy on Arterial and Cerebral Oxygenation During Laparoscopic Bariatric Surgery. AB - BACKGROUND: We investigated the effect of prolonged inspiratory to expiratory (I/E) ratio ventilation on respiratory mechanics, gas exchange, and regional cerebral oxygen saturation (rSO2) in obese patients undergoing laparoscopic bariatric surgery in the reverse Trendelenburg position. METHODS: Twenty-eight adult patients scheduled for laparoscopic sleeve gastrectomy were enrolled in this prospective observational study. After anesthesia induction, pressure controlled ventilation was conducted initially at a conventional I/E ratio of 1:2 and a positive end-expiratory pressure of 5 cmH2O. Twenty minutes after pneumoperitoneum, the I/E ratio was changed to 1:1 for 20 min and then to 2:1 for 20 min. Hemodynamic variables, end-tidal carbon dioxide tension, rSO2, arterial blood gas analysis results, and respiratory variables were recorded. RESULTS: No significant changes in hemodynamic values and rSO2 were observed during the study. Peak airway pressure was significantly lower, but mean airway pressure and dynamic compliance were significantly higher at I/E ratios of 1:1 and 2:1 than during conventional I/E ratio ventilation. Arterial oxygen tension (PaO2) value was significantly higher (p = 0.009), and alveolar-arterial oxygen tension gradient was lower (p = 0.015) at an I/E ratio of 2:1 than during conventional ratio ventilation. CONCLUSIONS: The use of prolonged I/E ratio of 2:1 significantly improved respiratory mechanics and arterial oxygenation without causing hemodynamic derangements or cerebral desaturation during laparoscopic bariatric surgery in the reverse Trendelenburg position. PMID- 26130180 TI - Biliopancreatic Diversion with Duodenal Switch in the Elderly: Long-Term Results of a Matched-Control Study. AB - BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) is one of the most effective surgical approaches for the treatment of severe obesity. OBJECTIVE: The objective of this study is to compare perioperative complications and long-term results of open BPD-DS in elderly versus younger patients. METHODS: All patients aged 60 years and above who underwent a primary open BPD-DS in our center were selected (n = 105). Patients were matched 1:1 for sex, BMI, the presence of type 2 diabetes (T2DM), and year of surgery with a group of younger patients (aged <=55 years). RESULTS: The mean age of the patients was 62.3 +/- 2.0 vs. 40.4 +/- 7.0 years (p <= 0.0001). Initial BMI and prevalence of T2DM were similar in both groups, at 50.9 kg/m(2) and 57%, respectively. Mean operative time (178.6 +/- 46.7 vs. 162.5 +/- 39.9 min, p = 0.01), hospital stay (10.2 +/- 8.3 vs. 6.3 +/- 1.5 days, p = 0.0001), and blood loss (593 +/- 484 vs. 474 +/- 241 ml, p = 0.05) were significantly higher in elderly patients. No difference in 30-day mortality rate was observed (0.9% in each group). There was no significant difference in major complication rate (16.2 vs. 8.6%, p = 0.09). At a mean follow up of 7.1 +/- 4.1 years, excess weight loss (67.6 +/- 19.2 vs. 72.7 +/- 20.7%, p = 0.06) and BMI (32.2 +/- 5.7 vs. 30.8 +/- 6.6 kg/m(2), p = 0.15) were not significantly different. No significant difference was observed between the two groups for the resolution of T2DM (p = 0.53) and obstructive sleep apnea (p = 0.44). CONCLUSIONS: Open BPD-DS is associated with similar long-term benefits in elderly and younger patients, in terms of weight loss and resolution or improvement of obesity-related comorbidities. Perioperative complications might be more frequent in the elderly population, but this was not associated with increased mortality. PMID- 26130181 TI - The EMG-MEP-outcomes relationship: it's complicated. PMID- 26130182 TI - Study on the temperature-dependent coupling among viscosity, conductivity and structural relaxation of ionic liquids. AB - The frequency-dependent viscosity and conductivity of three imidazolium-based ionic liquids were measured at several temperatures in the MHz region, and the results are compared with the intermediate scattering functions determined by neutron spin echo spectroscopy. The relaxations of both the conductivity and the viscosity agree with that of the intermediate scattering function at the ionic correlation when the relaxation time is short. As the relaxation time increases, the relaxations of the two transport properties deviate to lower frequencies than that of the ionic structure. The deviation begins at a shorter relaxation time for viscosity than for conductivity, which explains the fractional Walden rule between the zero-frequency values of the shear viscosity and the molar conductivity. PMID- 26130184 TI - What turns off the angiogenic switch in skeletal muscle? PMID- 26130183 TI - Role of habitual physical activity in modulating vascular actions of insulin. AB - NEW FINDINGS: What is the topic of this review? This review highlights the importance of increased vascular insulin sensitivity for maintaining glycaemic control and cardiovascular health. What advances does it highlight? We discuss the role of habitual physical activity in modulating vascular actions of insulin. Type 2 diabetes and cardiovascular disease commonly coexist. Current evidence suggests that impaired insulin signalling in the vasculature may be a common link between metabolic and cardiovascular diseases, including glycaemic dysregulation and atherosclerosis. Herein, we highlight the importance of the actions of insulin on the vasculature for glycaemic control and arterial health. In addition, we summarize and discuss findings from our group and others demonstrating that increased physical activity may be an effective approach to enhancing vascular insulin sensitivity. Furthermore, in light of the existing literature, we formulate the hypothesis that increased shear stress may be a prime mechanism through which habitual physical activity improves insulin signalling in the vasculature. Ultimately, we propose that targeting vascular insulin resistance may represent a viable strategy for improving glycaemic control and reducing cardiovascular risk in patients with type 2 diabetes. PMID- 26130185 TI - Taking steps in the workplace to improve vascular function. PMID- 26130187 TI - Current and Emerging Therapeutic Strategies for the Treatment of Meibomian Gland Dysfunction (MGD). AB - Meibomian gland (MG) dysfunction (MGD) is a multifactorial, chronic condition of the eyelids, leading to eye irritation, inflammation and ocular surface disease. Initial conservative therapy often includes a combination of warm compresses in addition to baby shampoo or eyelid wipes. The practice of lid hygiene dates back to the 1950s, when selenium sulfide-based shampoo was first used to treat seborrhoeic dermatitis of the eyelids. Today, tear-free baby shampoo has replaced dandruff shampoo for MGD treatment and offers symptom relief in selected patients. However, many will not achieve significant improvement on this therapy alone; some may even develop an allergy to the added dyes and fragrances in these products. Other manual and mechanical techniques to treat MGD include MG expression and massage, MG probing and LipiFlow((r)). While potentially effective in patients with moderate MGD, these procedures are more invasive and may be cost prohibitive. Pharmacological treatments are another course of action. Supplements rich in omega-3 fatty acids have been shown to improve both MGD and dry eye symptoms. Tea tree oil, specifically the terpenin-4-ol component, is especially effective in treating MGD associated with Demodex mites. Topical antibiotics, such as azithromycin, or systemic antibiotics, such as doxycycline or azithromycin, can improve MGD symptoms both by altering the ocular flora and through anti-inflammatory mechanisms. Addressing and treating concurrent ocular allergy is integral to symptom management. Topical N-acetylcysteine and topical cyclosporine can both be effective therapeutic adjuncts in patients with concurrent dry eye. A short course of topical steroid may be used in some severe cases, with monitoring for steroid-induced glaucoma and cataracts. While the standard method to treat MGD is simply warm compresses and baby shampoo, a more tailored approach to address the multiple aetiologies of the disease is suggested. PMID- 26130188 TI - Qualitative analysis of chemical constituents in traditional Chinese medicine analogous formula cheng-Qi decoctions by liquid chromatography-mass spectrometry. AB - Cheng-Qi decoctions (CQs), a group of analogous formulas, are well-known traditional Chinese preparations used as purgative remedies to treat 'internal heat'-induced symptoms, which manifest as a bloated and painful abdomen, hard stools, fever and other clinical observations. In this study, HPLC-ESI-MS/MS and UPLC-TOF-MS were employed for separation and structural identification of constituents in CQs. As a result, a total of 90 compounds, including seven anthraquinones, 39 flavones, 21 glycosides, 11 stilbene glycosides, six organic acids, five coumarins and one lignans, were detected and tentatively identified in CQs extracts. The characterization results shed some light on the scientific foundation for clinical application of the CQ analogous formulas. Our results also indicate that the HPLC-MS method is useful for the systemic identification of major constituents in traditional Chinese medicine formulas. PMID- 26130189 TI - Diterpenoid B derived from Plectranthus excisus inhibits the melanoma cell cycle in the B16 melanoma cell line. AB - Plectranthus excisus is widely distributed throughout northeast China. Its active ingredient, diterpenoids, exhibits significant antitumor effects. The present study examined the antitumor effects of diterpenoid B (DB), derived from Plectranthus excisus, and demonstrated that DB inhibited the proliferation of tumor cells by inhibiting the cell cycle. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to determine mRNA and protein expression levels, respectively. The results revealed that exposure to DB increased the expression levels of the transformation associated, protein 53, and cyclin-dependent kinase inhibitor 1A, and decreased the expression of cyclin-dependent kinase 2. The results of the present study demonstrated that DB can inhibit cell cycle progression and, therefore, offers potential as a beneficial antitumor drug. PMID- 26130190 TI - Rapid Adaptation of a Daphnia magna Population to Metal Stress Is Associated with Heterozygote Excess. AB - Although natural populations can harbor evolutionary potential to adapt genetically to chemical stress, it is often thought that natural selection leads to a general reduction of genetic diversity and involves costs. Here, a 10 week microevolution experiment was conducted with a genetically diverse and representative sample of one natural Daphnia magna population that was exposed to copper and zinc. Both Cu- and Zn-selected populations developed a significantly higher metal tolerance (i.e., genetic adaptation), indicated by higher reproduction probabilities of clonal lines in Cu and Zn exposures than observed for the original and control populations. The complete recovery of the population densities after 10 weeks of Zn selection (following an initial decrease of 74%) illustrates an example of evolutionary rescue. Microsatellite genotyping revealed a decrease in clonal diversity but no change in allelic richness, and showed an excess in heterozygosity in the Cu- and Zn-selected populations compared to the control and original populations. The excess heterozygosity in metal-selected populations that we observed has important consequences for risk assessment, as it contributes to the maintenance of a higher allelic diversity under multigenerational chemical exposure. This study is, to our knowledge, the first report of an increase in heterozygosity following multigenerational exposure to metal stress, despite a decline in clonal diversity. In a follow-up study with the Zn-selected populations, we observed no effect of Zn selection on the tolerance to heat and cyanobacteria. However, we observed higher tolerance to Cd in the Zn-selected than in the original and control populations if the 20% effective concentration of Cd was considered (cross-tolerance). Our results suggest only limited costs of adaptation but future research is needed to evaluate the adaptive potential of metal-selected populations to novel stressors and to determine to what extent increased heterozygosity is preserved after genetic recombination following periods of sexual reproduction. PMID- 26130191 TI - Oligomer Formation of Toxic and Functional Amyloid Peptides Studied with Atomistic Simulations. AB - Amyloids are associated with diseases, including Alzheimer's, as well as functional roles such as storage of peptide hormones. It is still unclear what differences exist between aberrant and functional amyloids. However, it is known that soluble oligomers formed during amyloid aggregation are more toxic than the final fibrils. Here, we perform molecular dynamics simulations to study the aggregation of the amyloid-beta peptide Abeta25-35, associated with Alzheimer's disease, and two functional amyloid-forming tachykinin peptides: kassinin and neuromedin K. Although the three peptides have similar primary sequences, tachykinin peptides, in contrast to Abeta25-35, form nontoxic amyloids. Our simulations reveal that the charge of the C-terminus is essential to controlling the aggregation process. In particular, when the kassinin C-terminus is not amidated, the aggregation kinetics decreases considerably. In addition, we observe that the monomeric peptides in extended conformations aggregate faster than those in collapsed hairpin-like conformations. PMID- 26130192 TI - "Boomerang Plus Sign" in Rickettsial Encephalitis. PMID- 26130193 TI - Comparison of in vitro methods for the production of Paenibacillus larvae endospores. AB - Paenibacillus larvae endospores are the infectious particles of the honey bee brood disease, American Foulbrood. We demonstrate that our previously published protocol (Alvarado et al., 2013) consistently yields higher numbers and purer preparations of P. larvae endospores, than previously described protocols, regardless of the strain tested (B-3650, B-3554 or B-3685). PMID- 26130194 TI - Evaluation of Learning in Oncology of Undergraduate Nursing with the Use of Concept Mapping. AB - This study aims to identify whether the use of concept mapping (CM) strategy assists a student to extend and revise their expertise in oncology and analyze the abilities developed in a student in order to go through theoretical to practical knowledge. This study is descriptive and qualitative, with 20 undergraduate students of the Undergraduate Nursing Course of Paulista School of Nursing of Federal University of Sao Paulo, Brazil. The critical incident technique and content analysis were used. There were 12 categories represented by facilities, difficulties, and learning applicability in oncology provided by CM strategy during the surgical and clinical nursing discipline. The graphics resource, CMapTools(r), and the clinical case data arranged in mapping for resolution generated an active search and exercise of self-learning in oncology. Despite the challenges of the use of CM as a teaching strategy-pedagogical, the results suggested an increase of autonomy and clinical reasoning in nursing practice. PMID- 26130195 TI - Intraguild interactions among specialised pollen feeders and generalist phytoseiids and their effect on citrus rust mite suppression. AB - BACKGROUND: Antagonistic interactions among predators with shared prey are thought to hamper their ability to suppress herbivores. Our aim was to quantify intraguild interactions in omnivorous predatory mite assemblages in the presence of pollen, and assess their effect on pest populations. We focused on the following naturally occurring phytoseiid species in Israeli citrus orchards and their ability to suppress a key pest, the citrus rust mite (CRM) Phyllocoptruta oleivora (Eriophyidae): the generalists Amblyseius swirskii and Typhlodromus athiasae and the specialised pollen feeders Iphiseius degenerans, Euseius scutalis, E. stipulatus and E. victoriensis. Evaluations were performed on two spatial scales, tree seedlings and leaf discs. RESULTS: On seedlings, experiments were conducted to quantify the interactions between predators in the presence of pollen and its effects on CRM suppression. On leaf discs, intraguild interactions were studied between pairs of phytoseiid species in the presence of pollen without CRM. On seedlings, the specialised pollen predators were more effective at suppressing CRM populations than the generalist predators. CONCLUSION: In most cases, the more aggressive intraguild predator was the specialised pollen feeder. Similarly, leaf-disc experiments suggest that in these interactions the specialised pollen feeders tend to be the intraguild predators more often than the intraguild prey. PMID- 26130196 TI - The Dynamic Influence of Genes and Environment in the Intergenerational Transmission of Anxiety. PMID- 26130197 TI - The Long and Winding Road to Bipolar Disorder. PMID- 26130198 TI - An Epidemiological Contribution to Clinical Understanding of Anxiety. PMID- 26130199 TI - The Path to Somewhere: Moving Toward a Better Biological Understanding of Irritability. PMID- 26130200 TI - The Alternative DSM-5 Model for Personality Disorders: A Clinical Application. PMID- 26130201 TI - We Should Talk About This. PMID- 26130202 TI - Alice Bennett, M.D., Ph.D.: A Woman of Firsts. PMID- 26130203 TI - Adjunctive Antipsychotic Prescriptions for Outpatients with Depressive Disorders in Asia: The Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) Study. PMID- 26130204 TI - Gluten-Free Diet Regimens and Psychiatric Symptoms. PMID- 26130205 TI - Response to Dell'Osso and Elli. PMID- 26130212 TI - Optical imaging probes for biomolecules: an introductory perspective. AB - An overview of optical biomolecular imaging is provided. Following a brief history of the development of probes and technologies in this area, general approaches which use biomolecular imaging in current commercial systems are discussed. A brief summary of research challenges in this area - in terms of both the chemistry and technique development - is introduced. Finally, areas rich for possible future development are suggested. PMID- 26130211 TI - A META-ANALYSIS OF COGNITIVE BEHAVIOR THERAPY AND MEDICATION FOR CHILD OBSESSIVE COMPULSIVE DISORDER: MODERATORS OF TREATMENT EFFICACY, RESPONSE, AND REMISSION. AB - BACKGROUND: Individual randomized controlled trials (RCTs) have demonstrated the efficacy of cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) for the treatment of youth with obsessive-compulsive disorder (OCD). Although meta-analyses have confirmed these results, there has been minimal examination of treatment moderators or an examination of treatment response and symptom/diagnostic remission for these two treatment types. The present report examined the treatment efficacy, treatment response, and symptom/diagnostic remission for youth with OCD receiving either CBT or SRIs relative to comparison conditions, and examined treatment moderators. METHOD: A comprehensive literature search identified 20 RCTs that met inclusion criteria, and produced a sample size of 507 CBT participants and 789 SRI participants. RESULTS: Random effects meta analyses of CBT trials found large treatment effects for treatment efficacy (g = 1.21), treatment response (relative risk [RR] = 3.93), and symptom/diagnostic remission (RR = 5.40). Greater co-occurring anxiety disorders, therapeutic contact, and lower treatment attrition were associated with greater CBT effects. The number needed to treat (NNT) was three for treatment response and symptom/diagnostic remission. Random effects meta-analyses of SRI trials found a moderate treatment effect for treatment efficacy (g = 0.50), treatment response (RR = 1.80), and symptom/diagnostic remission (RR = 2.06). Greater methodological quality was associated with a lower treatment response for SRI trials. The NNT was five for treatment response and symptom/diagnostic remission. CONCLUSIONS: Findings demonstrate the treatment effects for CBT and SRIs across three important outcome metrics, and provide evidence for moderators of CBT across trials. PMID- 26130213 TI - The cortical contrast accumulation from brain computed tomography after endovascular treatment predicts symptomatic hemorrhage. AB - BACKGROUND AND PURPOSE: The prognostic value of contrast accumulation from non contrast brain computed tomography taken immediately after endovascular reperfusion treatment in acute ischaemic stroke patients to predict symptomatic hemorrhage was studied. METHODS: Between July 2007 and August 2014, acute anterior circulation ischaemic stroke patients who were treated by intra-arterial thrombolysis or thrombectomy were included. Contrast accumulation was defined as a high attenuation area from non-contrast brain computed tomography immediately taken after endovascular reperfusion treatment, and patients were categorized into three groups according to the presence and location of contrast: (i) negative, (ii) cortical involvement and (iii) non-cortical involvement. The rates of symptomatic hemorrhage after 24 h and functional outcome at discharge were compared between patients with and without cortical involvement. RESULTS: Of 64 patients who were treated by endovascular intervention, contrast accumulation was detected in 56, including 33 patients with cortical involvement and 23 patients without cortical involvement. The cortical involvement pattern was more frequently associated with symptomatic hemorrhage (13 vs. 1 patient, P = 0.003) and with grave outcome at discharge with modified Rankin Scale 5 or 6 (14 vs. 4, P = 0.048) than the non-cortical involvement group. Multivariate logistic regression analysis including initial collateral status and occlusion site disclosed that cortical involvement pattern independently predicted symptomatic hemorrhage after endovascular treatment (odds ratio 19.0, confidence interval 1.6 227.6, P = 0.020). CONCLUSION: Our study provides evidence that the cortical involvement of contrast accumulation is associated with symptomatic hemorrhage after endovascular reperfusion treatment. PMID- 26130214 TI - Photoaggravated contact dermatitis to Kathon CG (methylchloroisothiazolinone/methylisothiazolinone): a novel pattern of involvement in a growing epidemic? PMID- 26130215 TI - Ultrasonographic findings in the ovine udder during lactogenesis in healthy ewes or ewes with pregnancy toxaemia. AB - Objective of the study was to record, by means of ultrasonographic examination, changes occurring during lactogenesis in the udder of healthy ewes and of ewes with pregnancy toxaemia. The work was carried out in 28 ewes, 16 with pregnancy toxaemia (group A) and 12 healthy controls (group B). B-mode and Doppler ultrasonographic examination of the udder of ewes was performed. During the last month of pregnancy, grey-scale intensity values of mammary parenchyma in group A were significantly greater than in group B (P = 0.007), as was also the progressive increase in grey-scale intensity values in both groups (P < 0.001). Blood mammary input was significantly greater in ewes of group B than in ewes of group A (P < 0.05), as was also the progressive increase in blood input in both groups (P < 0.001). Further, differences between the two groups were identified in pulsatility index (P = 0.007) and in mean blood velocity (P = 0.036), but only during the last fortnight of pregnancy. After lambing, grey-scale values decreased sharply compared to those in pregnancy (P < 0.01), whilst blood input, pulsatility index and mean blood velocity continued the same trend as at the last stage of pregnancy, with differences between the two groups still prevalent (P < 0.05). There was a reverse correlation between grey-scale intensity values and milk quantities (P < 0.035) and a correlation between blood input and milk quantities (P < 0.07). The progressive increase in the diameter of the external pudendal artery was significant (P < 0.001), but no significant differences were evident between the two groups (P > 0.35). Differences between group A and group B in all other haemodynamic parameters studied were not significant, neither throughout the last month of pregnancy (P > 0.25), nor during the first week of lactation (P > 0.06). However, their progressive changes during the last month of pregnancy were significant (P < 0.02). PMID- 26130217 TI - Synthesis of Bismuth-Nanoparticle-Enriched Nanoporous Carbon on Graphene for Efficient Electrochemical Analysis of Heavy-Metal Ions. AB - A BiNPs@NPCGS nanocomposite was designed for highly efficient detection of multiple heavy-metal ions by in situ synthesis of bismuth-nanoparticle (BiNP) enriched nanoporous carbon (NPS) on graphene sheet (GS). The NPCGS was prepared by pyrolysis of zeolitic imidazolate framework-8 (ZIF-8) nanocrystals deposited on graphene oxide and displayed a high surface area of 1251 m(2) g(-1) and a pore size of 3.4 nm. BiNPs were deposited on NPCGS in situ by chemical reduction of Bi(3+) with NaBH4 . Due to the restrictive effect of the pore/surface structure of NPCGS, the BiNPs were uniform and well dispersed on the NPCGS. The BiNPs@NPCGS showed good conductivity and high effective area, and the presence of BiNPs allowed it to act as an efficient material for anodic-stripping voltammetric detection of heavy-metal ions. Under optimized conditions, the BiNPs@NPCGS-based sensor could simultaneously determine Pb(2+) and Cd(2+) with detection limits of 3.2 and 4.1 nM, respectively. Moreover, the proposed sensor could also differentiate Tl(+) from Pb(2+) and Cd(2+). Owing to its advantages of simple preparation, environmental friendliness, high surface area, and fast electron-transfer ability, BiNPs@NPCGS showed promise for practical application in sensing heavy-metal ions. PMID- 26130216 TI - Magnetic resonance elastography of frontotemporal dementia. AB - PURPOSE: To investigate the feasibility of utilizing brain stiffness as a potential biomarker for behavioral variant frontotemporal dementia (bvFTD) patients. Magnetic resonance elastography (MRE) is a noninvasive technique for evaluating the mechanical properties of brain tissue in vivo. MRE has demonstrated decreased brain stiffness in patients with Alzheimer's disease. MATERIALS AND METHODS: We examined five male subjects with bvFTD and nine cognitively normal age-matched male controls (NC) with brain 3T MRE. Stiffness was calculated in nine regions of interest (ROIs): whole brain (entire cerebrum excluding cerebellum), frontal lobes, occipital lobes, parietal lobes, temporal lobes, deep gray matter / white matter (GM/WM; insula, deep gray nuclei and white matter tracts), cerebellum, sensorimotor cortex (pre- and postcentral gyri), and a composite region labeled FT (frontal and temporal lobes excluding the pre- and postcentral gyri). RESULTS: Significantly lower stiffness values were observed in the whole brain (P = 0.007), frontal lobe (P = 0.001), and temporal lobes (P = 0.005) of bvFTD patients compared to NC. No significant stiffness differences were observed in any other ROIs of bvFTD patients compared to NC (P > 0.05). These results demonstrate that statistically significant brain softening occurs in the frontal and temporal lobes of bvFTD patients, which corresponds to the expected pathophysiology of bvFTD. CONCLUSION: Future studies evaluating the feasibility of brain MRE for early disease detection and monitoring disease progression could shed new insights into understanding the mechanisms involved in bvFTD. PMID- 26130218 TI - Collagenous colitis with mucosal ulcerations in a patient without nonsteroidal anti-inflammatory drug or lansoprazole use. AB - Chronic watery diarrhea combined with normal-appearing colonic mucosa at endoscopy with abnormal histopathology is classified as microscopic colitis. Microscopic colitis encompasses both collagenous and lymphocytic colitis. A 42 year-old Caucasian woman presented with severe diarrhea for six weeks with loose watery stools every 1-2 h, approximately 15 episodes per day. She denied any melena or significant abdominal pain. She denied nonsteroidal anti-inflammatory drug or lansoprazole use, and was only taking diphenoxylate/atropine for her symptoms. Colonoscopy revealed superficial ulcerations in the distal ascending and transverse colon and scattered ulcerations in the descending and sigmoid colon, with biopsy confirming collagenous colitis. We report a rare case of collagenous colitis accompanied by mucosal ulcerations in the absence of known culprits of mucosal ulcerations, such as nonsteroidal anti-inflammatory drugs or lansoprazole. PMID- 26130219 TI - Hot Off the Press: Subdissociative-dose Ketamine for Acute Pain in the Emergency Department. PMID- 26130220 TI - Effect of antibiotics on cellular stress generated in Shiga toxin-producing Escherichia coli O157:H7 and non-O157 biofilms. AB - Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, with the main virulence factor of this bacterium being its capacity to secrete Shiga toxins (Stxs). Therefore, the use of certain antibiotics for the treatment of this infection, which induces the liberation of Stxs, is controversial. Reactive oxygen and nitrogen species are also involved in the pathogenesis of different diseases. The purpose of this study was to analyze the effects of antibiotics on biofilms of STEC and the relationships between cellular stress and the release of Stx. To this end, biofilms of reference and clinical strains were treated with antibiotics (ciprofloxacin, fosfomycin and rifaximin) and the production of oxidants, the antioxidant defense system and toxin release were evaluated. Ciprofloxacin altered the prooxidant-antioxidant balance, with a decrease of oxidant metabolites and an increase of superoxide dismutase and catalase activity, being associated with high-levels of Stx production. Furthermore, inhibition of oxidative stress by exogenous antioxidants was correlated with a reduction in the liberation of Stx, indicating the participation of this phenomenon in the release of this toxin. In contrast, fosfomycin and rifaximin produced less alteration with a minimal production of Stx. Our data show that treatment of biofilm-STEC with these antibiotics induces oxidative stress-mediated release of Stx. PMID- 26130221 TI - Valve-in-valve Medtronic CoreValve implantation into a degenerated transapical Ventor Embracer aortic valve bioprosthesis. PMID- 26130222 TI - The Family and Medical Leave Act Should Be Applicable to All Radiologists and Radiation Oncologists. PMID- 26130223 TI - Code Abdomen: An Assessment Coding Scheme for Abdominal Imaging Findings Possibly Representing Cancer. PMID- 26130224 TI - Investigation of the mechanism of interaction between Mannose-binding lectin associated serine protease-2 and complement C4. AB - The interaction between mannose-binding lectin [MBL]-associated serine protease-2 (MASP-2) and its first substrate, C4 is crucial to the lectin pathway of complement, which is vital for innate host immunity, but also involved in a number of inflammatory diseases. Recent data suggests that two areas outside of the active site of MASP-2 (so-called exosites) are crucial for efficient cleavage of C4: one at the junction of the two complement control protein (CCP) domains of the enzyme and the second on the serine protease (SP) domain. Here, we have further investigated the roles of each of these exosites in the binding and cleavage of C4. We have found that both exosites are required for high affinity binding and efficient cleavage of the substrate protein. Within the SP domain exosite, we have shown here that two arginine residues are most important for high affinity binding and efficient cleavage of C4. Finally, we show that the CCP domain exosite appears to play the major role in the initial interaction with C4, whilst the SP domain exosite plays the major role in a secondary conformational change between the two proteins required to form a high affinity complex. This data has provided new insights into the binding and cleavage of C4 by MASP-2, which may be useful in the design of molecules that modulate this important interaction required to activate the lectin pathway of complement. PMID- 26130225 TI - Soluble RAGEs - Prospects for treating & tracking metabolic and inflammatory disease. AB - Emerging evidence links the receptor for advanced glycation endproducts (RAGE) to the pathogenesis of tissue damage in chronic metabolic and inflammatory diseases. In human subjects, multiple reports suggest that in the plasma/serum, circulating levels of distinct forms of soluble RAGEs may be biomarkers of the presence or absence, and the extent of chronic disease. These considerations prompt us to consider in this review, what are soluble RAGEs; how are they formed; what might be their natural functions; and may they serve as biomarkers of inflammatory and metabolic disease activity? In this brief review, we seek to address what is known and suggest new areas for scientific investigation to uncover the biology of soluble RAGEs. PMID- 26130226 TI - CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients. AB - INTRODUCTION: Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients. METHOD: We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection. DISCUSSION: Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called "inflammaging." Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults. CONCLUSION: The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune based clinical trials. PMID- 26130227 TI - Islamic State creates jihadi health service. PMID- 26130228 TI - Time for tighter checks on medical schools? PMID- 26130229 TI - The changing characteristics of atrial fibrillation patients treated with warfarin. AB - It has been suggested that direct oral anticoagulants are being preferentially used in low risk atrial fibrillation (AF) patients. Understanding the changing risk profile of new AF patients treated with warfarin is important for interpreting the quality of warfarin delivery through an anticoagulation clinic. Six anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative enrolled 1293 AF patients between 2010 and 2014 as an inception cohort. Abstracted data included demographics, comorbidities, medication use and all INR values. Risk scores including CHADS2, CHA2DS2-VASc, HAS-BLED, SAMe-TT2R2, and Charlson comorbidity index (CCI) were calculated for each patient at the time of warfarin initiation. The quality of anticoagulation was assessed using the Rosendaal time in the therapeutic range (TTR) during the first 6 months of treatment. Between 2010 and 2014, patients initiating warfarin therapy for AF had an increasing mean CHADS2 (2.0 +/- 1.1 to 2.2 +/- 1.4, p = 0.02) and CCI (4.7 +/- 1.8 to 5.1 +/- 2.0, p = 0.03), and a trend towards increasing mean CHA2DS2-VASc, HAS-BLED, and SAMe-TT2R2 scores. The actual TTR remained unchanged over the study period (62.6 +/- 18.2 to 62.7 +/- 17.0, p = 0.98), and the number of INR checks did not change (18.9 +/- 5.2 to 18.5 +/- 5.1, p = 0.06). Between 2010 and 2014, AF patients newly starting warfarin had mild increases in risk for stroke and death with sustained quality of warfarin therapy. PMID- 26130230 TI - Clinical Outcomes of Computed Tomography-Based Volumetric Brachytherapy Planning for Cervical Cancer. AB - PURPOSE/OBJECTIVES: A report of clinical outcomes of a computed tomography (CT) based image guided brachytherapy (IGBT) technique for treatment of cervical cancer. METHODS AND MATERIALS: Seventy-six women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma diagnosed between 2007 and 2014 were treated with definitive external beam radiation therapy (EBRT) with or without concurrent chemotherapy followed by high-dose-rate (HDR) IGBT. All patients underwent planning CT simulation at each implantation. A high-risk clinical target volume (HRCTV) encompassing any visible tumor and the entire cervix was contoured on the simulation CT. When available, magnetic resonance imaging (MRI) was performed at implantation to assist with tumor delineation. The prescription dose was prescribed to the HRCTV. RESULTS: The median follow-up time was 17 months. Thirteen patients (17%) had an MRI done before brachytherapy, and 16 patients (21%) were treated without MRI guidance. The mean EBRT/IGBT sum 2-Gy equivalent dose (EQD2) delivered to the 90% volume of the HRCTV was 86.3 Gy. The mean maximum EQD2s delivered to 2 cm(3) of the rectum, sigmoid, and bladder were 67.5 Gy, 66.2 Gy, and 75.3 Gy, respectively. The 2-year cumulative incidences of local, locoregional, and distant failure were 5.8% (95% confidence interval [CI]: 1.4%-14.8%), 15.1% (95% CI: 5.4%-29.4%), and 24.3% (95% CI: 12.1%-38.9%), respectively. The 2-year overall and disease-free survival rates were 75% (95% CI, 61%-91%) and 73% (95% CI, 60%-90%), respectively. Twenty-nine patients (38%) experienced grade >= 2 acute toxicity, with 5 cases of acute grade 3 toxicity and no grade >= 4 toxicities. One patient experienced grade 3 gastrointestinal toxicity. No other late grade >= 3 events were observed. CONCLUSIONS: This is the largest report to date of CT/MRI-based IGBT for the treatment of cervical cancer. The results are promising, with excellent local control and acceptable toxicity. Further investigation is needed to assess the long-term safety and efficacy of this treatment. PMID- 26130231 TI - Creation of a Prognostic Index for Spine Metastasis to Stratify Survival in Patients Treated With Spinal Stereotactic Radiosurgery: Secondary Analysis of Mature Prospective Trials. AB - PURPOSE: There exists uncertainty in the prognosis of patients following spinal metastasis treatment. We sought to create a scoring system that stratifies patients based on overall survival. METHODS AND MATERIALS: Patients enrolled in 2 prospective trials investigating stereotactic spine radiation surgery (SSRS) for spinal metastasis with >= 3-year follow-up were analyzed. A multivariate Cox regression model was used to create a survival model. Pretreatment variables included were race, sex, age, performance status, tumor histology, extent of vertebrae involvement, previous therapy at the SSRS site, disease burden, and timing of diagnosis and metastasis. Four survival groups were generated based on the model-derived survival score. RESULTS: Median follow-up in the 206 patients included in this analysis was 70 months (range: 37-133 months). Seven variables were selected: female sex (hazard ratio [HR] = 0.7, P=.02), Karnofsky performance score (HR = 0.8 per 10-point increase above 60, P = .007), previous surgery at the SSRS site (HR = 0.7, P=.02), previous radiation at the SSRS site (HR = 1.8, P=.001), the SSRS site as the only site of metastatic disease (HR = 0.5, P=.01), number of organ systems involved outside of bone (HR = 1.4 per involved system, P<.001), and >5 year interval from initial diagnosis to detection of spine metastasis (HR = 0.5, P < .001). The median survival among all patients was 25.5 months and was significantly different among survival groups (in group 1 [excellent prognosis], median survival was not reached; group 2 reached 32.4 months; group 3 reached 22.2 months; and group 4 [poor prognosis] reached 9.1 months; P < .001). Pretreatment symptom burden was significantly higher in the patient group with poor survival than in the group with excellent survival (all metrics, P < .05). CONCLUSIONS: We developed the prognostic index for spinal metastases (PRISM) model, a new model that identified patient subgroups with poor and excellent prognoses. PMID- 26130232 TI - Methionine Uptake and Required Radiation Dose to Control Glioblastoma. AB - PURPOSE: The purpose of this study was to retrospectively assess the feasibility of radiation therapy planning for glioblastoma multiforme (GBM) based on the use of methionine (MET) positron emission tomography (PET), and the correlation among MET uptake, radiation dose, and tumor control. METHODS AND MATERIALS: Twenty-two patients with GBM who underwent MET-PET prior to radiation therapy were enrolled. MET uptake in 30 regions of interest (ROIs) from 22 GBMs, biologically effective doses (BEDs) for the ROIs and their ratios (MET uptake:BED) were compared in terms of whether the ROIs were controlled for >12 months. RESULTS: MET uptake was significantly correlated with tumor control (odds ratio [OR], 10.0; P = .005); however, there was a higher level of correlation between MET uptake:BED ratio and tumor control (OR, 40.0; P < .0001). These data indicated that the required BEDs for controlling the ROIs could be predicted in terms of MET uptake; BED could be calculated as [34.0 * MET uptake] Gy from the optimal threshold of the MET uptake:BED ratio for tumor control. CONCLUSIONS: Target delineation based on MET PET was demonstrated to be feasible for radiation therapy treatment planning. MET PET could not only provide precise visualization of infiltrating tumor cells but also predict the required radiation doses to control target regions. PMID- 26130233 TI - Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients. AB - PURPOSE: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS). METHODS AND MATERIALS: We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n = 42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy). RESULTS: Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P < .001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P < .001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P < .001) and RT dose of >= 60 Gy (P < .001). CONCLUSIONS: Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended. PMID- 26130234 TI - Flexible thermoplastic resin to add retention to tooth-supported stereolithographic surgical guides. AB - Surgical guides produced by stereolithography use hard resin. The hard resin prevents seating beyond the height of contour, hence these guides are not intrinsically retentive. By covering the guide with a flexible thermoplastic material that extends into the undercuts, the resulting guide now has a retentive feature. This allows it to maintain its position during surgery yet it can easily be removed and repositioned. PMID- 26130235 TI - Fabricating short-term interim restorations from edentulous tissue conditioner material. PMID- 26130236 TI - Integrating Sequence Evolution into Probabilistic Orthology Analysis. AB - Orthology analysis, that is, finding out whether a pair of homologous genes are orthologs - stemming from a speciation - or paralogs - stemming from a gene duplication - is of central importance in computational biology, genome annotation, and phylogenetic inference. In particular, an orthologous relationship makes functional equivalence of the two genes highly likely. A major approach to orthology analysis is to reconcile a gene tree to the corresponding species tree, (most commonly performed using the most parsimonious reconciliation, MPR). However, most such phylogenetic orthology methods infer the gene tree without considering the constraints implied by the species tree and, perhaps even more importantly, only allow the gene sequences to influence the orthology analysis through the a priori reconstructed gene tree. We propose a sound, comprehensive Bayesian Markov chain Monte Carlo-based method, DLRSOrthology, to compute orthology probabilities. It efficiently sums over the possible gene trees and jointly takes into account the current gene tree, all possible reconciliations to the species tree, and the, typically strong, signal conveyed by the sequences. We compare our method with PrIME-GEM, a probabilistic orthology approach built on a probabilistic duplication-loss model, and MrBayesMPR, a probabilistic orthology approach that is based on conventional Bayesian inference coupled with MPR. We find that DLRSOrthology outperforms these competing approaches on synthetic data as well as on biological data sets and is robust to incomplete taxon sampling artifacts. PMID- 26130237 TI - Ubiquinol (reduced Coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial. AB - INTRODUCTION: We previously found decreased levels of Coenzyme Q10 (CoQ10) in patients with septic shock. The objective of the current study was to assess whether the provision of exogenous ubiquinol (the reduced form of CoQ10) could increase plasma CoQ10 levels and improve mitochondrial function. METHODS: We performed a randomized, double-blind, pilot trial at a single, tertiary care hospital. Adults (age >=18 years) with severe sepsis or septic shock between November 2012 and January 2014 were included. Patients received 200 mg enteral ubiquinol or placebo twice a day for up to seven days. Blood draws were obtained at baseline (0 h), 12, 24, 48, and 72 h. The primary outcome of the study was change in plasma CoQ10 parameters (total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10). Secondary outcomes included assessment of: 1) vascular endothelial biomarkers, 2) inflammatory biomarkers, 3) biomarkers related to mitochondrial injury including cytochrome c levels, and 4) clinical outcomes. CoQ10 levels and biomarkers were compared between groups using repeated measures models. RESULTS: We enrolled 38 patients: 19 in the CoQ10 group and 19 in the placebo group. The mean patient age was 62 +/ 16 years and 47% were female. Baseline characteristics and CoQ10 levels were similar for both groups. There was a significant increase in total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10 in the ubiquinol group compared to the placebo group. We found no difference between the two groups in any of the secondary outcomes. CONCLUSIONS: In this pilot trial we showed that plasma CoQ10 levels could be increased in patients with severe sepsis or septic shock, with the administration of oral ubiquinol. Further research is needed to address whether ubiquinol administration can result in improved clinical outcomes in this patient population. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01948063. Registered on 18 February 2013. PMID- 26130238 TI - RFamide peptides in agnathans and basal chordates. AB - Since a peptide with a C-terminal Arg-Phe-NH2 (RFamide peptide) was first identified in the ganglia of the venus clam in 1977, RFamide peptides have been found in the nervous system of both invertebrates and vertebrates. In vertebrates, the RFamide peptide family includes gonadotropin-inhibitory hormone (GnIH), neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP), pyroglutamylated RFamide peptide/26RFamide peptide (QRFP/26RFa), and kisspeptins (kiss1 and kiss2). They are involved in important functions such as the release of hormones, regulation of sexual or social behavior, pain transmission, reproduction, and feeding. In contrast to tetrapods and jawed fish, the information available on RFamide peptides in agnathans and basal chordates is limited, thus preventing further insights into the evolution of RFamide peptides in vertebrates. In this review, we focus on the previous research and recent advances in the studies on RFamide peptides in agnathans and basal chordates. In agnathans, the genes encoding GnIH, NPFF, and PrRP precursors and the mature peptides have been identified in lamprey (Petromyzon marinus) and hagfish (Paramyxine atami). Putative kiss1 and kiss2 genes have also been found in the genome database of lamprey. In basal chordates, namely, in amphioxus (Branchiostoma japonicum), a common ancestral form of GnIH and NPFF genes and their mature peptides, as well as the ortholog of the QRFP gene have been identified. The studies revealed that the number of orthologs of vertebrate RFamide peptides present in agnathans and basal chordates is greater than expected, suggesting that the vertebrate RFamide peptides might have emerged and expanded at an early stage of chordate evolution. PMID- 26130239 TI - Identification and localization of gonadotropin-inhibitory hormone (GnIH) orthologs in the hypothalamus of the red-eared slider turtle, Trachemys scripta elegans. AB - Gonadotropin-inhibitory hormone (GnIH) was discovered in 2000 as a novel hypothalamic neuropeptide that inhibited gonadotropin release in the Japanese quail. GnIH and its orthologs have a common C-terminal LPXRFamide (X=L or Q) motif, and have been identified in vertebrates from agnathans to humans, apart from reptiles. In the present study, we characterized a cDNA encoding GnIH orthologs in the brain of the red-eared slider turtle. The deduced precursor protein consisted of 205 amino-acid residues, encoding three putative peptide sequences that included the LPXRFamide motif at their C-termini. In addition, the precursor sequence was most similar to those of avian species. Immunoaffinity purification combined with mass spectrometry confirmed that three mature peptides were produced in the brain. In situ hybridization and immunohistochemistry showed that turtle GnIH-containing cells were restricted to the periventricular hypothalamic nucleus. Immunoreactive fibers were densely distributed in the median eminence. Thus, GnIH and related peptides may act on the pituitary to regulate pituitary hormone release in turtles as well as other vertebrates. PMID- 26130240 TI - Correlation between three-dimentional surface topography and color stability of different nanofilled composites. AB - AIM: The aim of this study was to evaluate the 3-dimensional (3D) surface topography and color stability of four different resin composites after immersion in different soft-beverages. MATERIALS AND METHODS: One hundred sixty disk-shaped specimens (diameter: 10 mm, and thickness: 2 mm) were made from four different resin composites (i.e., Filtek Z550, Tetric N-Ceram, Clearfil Majesty Esthetic, and Cavex Quadrant Universal LC). Each specimen was cured under mylar strips for 20 sec for both top and bottom surfaces. All of the specimens were stored in distilled water for 24 h at 37 degrees C. Surface measurements were carried out using a noncontact 3D-optical-profilometer in terms of surface topography (Ra values). Color measurements of each specimen were performed with Vita Easy Shade system. All the measurements were performed at baseline and after 30 days of immersion in the selected soft-beverages (Redbull, Coca-Cola and Dimes-Lemonade). Control groups were stored in distilled water during the study. Ra values and color changes (DeltaE values) of the groups were recorded. The data were statistically analyzed using a one way ANOVA and Tukey's post-hoc tests (SPSS 18.0). RESULTS: The tested soft-beverages in the present study caused color changes at a 30-day evaluation period for the tested resin composites (p < 0.05). However, 3D surface topography of resin composites was not influenced by the tested soft-beverages (p > 0.05). There was no significant interaction between the composite and beverage type on the Ra values of the resin composites (p > 0.05). CONCLUSIONS: No correlation was found between color stability and 3D surface topography of the resin composites. Color stability of resin composites may be affected by soft beverages. PMID- 26130241 TI - Sepsis-induced immune alterations monitoring by flow cytometry as a promising tool for individualized therapy. AB - Septic syndromes remain a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units. While sepsis has, for long, been solely described as inducing a tremendous systemic inflammatory response, novel findings indicate that sepsis indeed initiates a more complex immunologic response that varies over time, with the concomitant occurrence of both pro- and anti-inflammatory mechanisms. As a resultant, after a short proinflammatory phase, septic patients enter a stage of protracted immunosuppression. This is illustrated in those patients by reactivation of dormant viruses (CMV or HSV) or infections due to pathogens, including fungi, which are normally pathogenic solely in immunocompromised hosts. Although mechanisms are not totally understood, these alterations might be directly responsible for worsening outcome in patients who survived initial resuscitation as nearly all immune functions are deeply compromised. Indeed, the magnitude and persistence over time of these dysfunctions have been associated with increased mortality and health-care associated infection rate. Consequently, new promising therapeutic avenues are currently emerging from those recent findings such as adjunctive immunostimulation (IFN-gamma, GM-CSF, IL-7, anti-PD1/L1 antibodies) for the most immunosuppressed patients. Nevertheless, as there is no clinical sign of immune dysfunctions, the prerequisite for such therapeutic intervention relies on our capacity in identifying the patients who could benefit from immunostimulation. To date, the most robust biomarkers of sepsis-induced immunosuppression are measured by flow cytometry. Of them, the decreased expression of monocyte HLA-DR appears as a "gold standard." This review reports on the mechanisms sustaining sepsis-induced immunosuppression and its related biomarkers measurable by flow cytometry. The objective is to integrate the most recent facts in an up-to-date account of clinical results, flow cytometry aspects as well as issues in results standardization for multicenter studies. (c) 2015 International Clinical Cytometry Society. PMID- 26130242 TI - Spatio-temporal distribution of chlorophyll-a in relation to physico-chemical parameters in coastal waters of the northwestern Bay of Bengal. AB - The present study focuses on understanding the long-term distribution of physico chemical parameters and their influence on the distribution of chlorophyll-a (chl a) at a coastal site in the northwestern Bay of Bengal. Chl-a showed large variability (0.12 to 10.05 mg m(-3)) on a spatio-temporal scale during the study period. However, the distribution showed a similar pattern with marginal variability from March 2010 to February 2011 and March 2011 to February 2012. The vertical distribution of salinity, pH, total suspended matter (TSM) and chl-a showed systematic temporal variability. However, dissolved oxygen (DO) and nutrients (nitrite + nitrate, phosphate, silicate) did not show any significant spatio-temporal trend. Chl-a showed bimodal distribution on an annual scale, with the first peak appearing during the pre-monsoon period in March due to a seasonal phytoplankton bloom, whereas the second peak occurring during September as a result of nutrient loading from river influx due to monsoonal precipitation. Factor analysis revealed the association of low salinity and high nutrients with chl-a. This infers that the nutrients brought by the influx of river into the study area were fuelling the growth and abundance of phytoplankton. Cluster analysis resulted in two distinct clusters among all physico-chemical datasets, indicating the presence of two distinct areas separated by the 30 m isobath that were strongly influenced by physico-chemical characteristics associated with the seasonal monsoon. PMID- 26130243 TI - Using wavelet-feedforward neural networks to improve air pollution forecasting in urban environments. AB - The paper presents the screening of various feedforward neural networks (FANN) and wavelet-feedforward neural networks (WFANN) applied to time series of ground level ozone (O3), nitrogen dioxide (NO2), and particulate matter (PM10 and PM2.5 fractions) recorded at four monitoring stations located in various urban areas of Romania, to identify common configurations with optimal generalization performance. Two distinct model runs were performed as follows: data processing using hourly-recorded time series of airborne pollutants during cold months (O3, NO2, and PM10), when residential heating increases the local emissions, and data processing using 24-h daily averaged concentrations (PM2.5) recorded between 2009 and 2012. Dataset variability was assessed using statistical analysis. Time series were passed through various FANNs. Each time series was decomposed in four time-scale components using three-level wavelets, which have been passed also through FANN, and recomposed into a single time series. The agreement between observed and modelled output was evaluated based on the statistical significance (r coefficient and correlation between errors and data). Daubechies db3 wavelet Rprop FANN (6-4-1) utilization gave positive results for O3 time series optimizing the exclusive use of the FANN for hourly-recorded time series. NO2 was difficult to model due to time series specificity, but wavelet integration improved FANN performances. Daubechies db3 wavelet did not improve the FANN outputs for PM10 time series. Both models (FANN/WFANN) overestimated PM2.5 forecasted values in the last quarter of time series. A potential improvement of the forecasted values could be the integration of a smoothing algorithm to adjust the PM2.5 model outputs. PMID- 26130244 TI - Metal distribution in soils of an in-service urban parking lot. AB - Increasing traffic is becoming one of the main sources of metal pollution in urban areas. To investigate the possible impacts of traffic-related activities on metal distribution in soils, a total of 370 soil samples were collected in a ground parking space in service for about 20 years in Chengdu, China. The concentrations of Cu, Fe, Mn, Pb, Rb, Sr, Ti, and Zn in soils were measured using portable energy-dispersive X-ray fluorescence. Soil samples exhibited various levels of metal pollution ranging from no pollution to borderline moderate pollution for Zn and Pb, with median enrichment factors following the order of Zn (2.7), Pb (2.2), Sr (1.9), Cu (1.8), Fe (1.3), Rb (1.1), and Mn (0.5). Both cluster analysis and spatial distribution mapping demonstrated that Pb, Zn, Cu, Mn, Sr, and Fe concentrations in the parking space were influenced by traffic, with strong spatial variation in different areas of the parking space. These metals shared similar spatial distribution patterns with relatively elevated concentrations in the four corners, left and right sides and entrance and rear areas, compared with the metal concentrations in the central area. Such spatial patterns revealed the influences of yellow road paint, wear and tear of vehicular parts including brakes and tires, as well as tailpipe emissions. The pollution sources in the parking space were identified as yellow road paint and vehicular emissions. This study highlights that metal pollution in the parking areas should be given more attention. PMID- 26130245 TI - The dissolved organic matter as a potential soil quality indicator in arable soils of Hungary. AB - Although several authors have suggested that the labile fraction of soils could be a potential soil quality indicator, the possibilities and limitations of using the dissolved organic matter (DOM) fraction for this purpose have not yet been investigated. The objective of this study was to evaluate the hypothesis that DOM is an adequate indicator of soil quality. To test this, the soil quality indices (SQI) of 190 arable soils from a Hungarian dataset were estimated, and these values were compared to DOM parameters (DOC and SUVA254). A clear difference in soil quality was found between the soil types, with low soil quality for arenosols (average SQI 0.5) and significantly higher values for gleysols, vertisols, regosols, solonetzes and chernozems. The SQI-DOC relationship could be described by non-linear regression, while a linear connection was observed between SQI and SUVA. The regression equations obtained for the dataset showed only one relatively weak significant correlation between the variables, for DOC (R (2) = 0.157(***); n = 190), while non-significant relationships were found for the DOC and SUVA254 values. However, an envelope curve operated with the datasets showed the robust potential of DOC to indicate soil quality changes, with a high R (2) value for the envelope curve regression equation. The limitations to using the DOM fraction of soils as a quality indicator are due to the contradictory processes which take place in soils in many cases. PMID- 26130246 TI - Exploring the possibility to detect recent temporal changes in highly disturbed sedimentary records through sampling repetitions and core comparisons of porosity and sand content. AB - Dating of sediment cores in dynamic environments (such as tropical coastal lagoons) is often impossible to achieve, due to the difficulty to recover continuous and undisturbed records. Detailed temporal definition of environmental changes cannot be assured, but there is the possibility that information retained in such sediments can still provide useful insights on local or large-scale sedimentary dynamics, when a specific strategy is adopted. This latter consists in repeated core samplings at the same location and in the comparison of core profiles for basic and easily measurable parameters (porosity and sand content). This approach was tested on sediment cores, collected repeatedly during the period 2005-2010, at the same site of the Thi Nai Lagoon (central Vietnam). The proposed procedure was able to evidence the impact on lagoon sediments of activities linked to the construction of industrial settlements in the area, with dredging removing a consistent sediment layer from 2005 to 2008 and waste dumping providing additional sediment input in the following period. Simple statistic confirmed this scenario, together with core profiles of PCBs, As, Cd, Pb, and Zn. The procedure represents a simple tool to study coastal dynamics in places where the level of accuracy of traditional sediment radiodating cannot be reached. Several ameliorations are suggested in order to help developing the monitoring of sedimentary processes in poorly studied areas. PMID- 26130247 TI - Metabolic networks in a porcine model of trauma and hemorrhagic shock demonstrate different control mechanism with carbohydrate pre-feed. AB - BACKGROUND: Treatment with oral carbohydrate prior to trauma and hemorrhage confers a survival benefit in small animal models. The impact of fed states on survival in traumatically injured humans is unknown. This work uses regulatory networks to examine the effect of carbohydrate pre-feeding on metabolic response to polytrauma and hemorrhagic shock in a clinically-relevant large animal model. METHODS: Male Yorkshire pigs were fasted overnight (n = 64). Pre-fed animals (n = 32) received an oral bolus of Karo?textregistered?syrup before sedation. All animals underwent a standardized trauma, hemorrhage, and resuscitation protocol. Serum samples were obtained at set timepoints. Proton NMR was used to identify and quantify serum metabolites. Metabolic regulatory networks were constructed from metabolite concentrations and rates of change in those concentrations to identify controlled nodes and controlling nodes of the network. RESULTS: Oral carbohydrate pre-treatment was not associated with survival benefit. Six metabolites were identified as controlled nodes in both groups: adenosine, cytidine, glycerol, hypoxanthine, lactate, and uridine. Distinct groups of controlling nodes were associated with controlled nodes; however, the composition of these groups depended on feeding status. CONCLUSIONS: A common metabolic output, typically associated with injury and hypoxia, results from trauma and hemorrhagic shock. However, this output is directed by different metabolic inputs depending upon the feeding status of the subject. Nodes of the network that are related to mortality can potentially be manipulated for therapeutic effect; however, these nodes differ depending upon feeding status. PMID- 26130248 TI - Whether or not to accept a deceased donor kidney offer for a pediatric patient. AB - The expansion of the number of children on the deceased donor renal transplant waitlist has far outstripped the supply of organs in most countries, leading to numerous adjustments to increase supply and to maximize the utility of donor organs. The system for organ allocation varies by country based on local laws, priorities, and resources. Adjustments are made to optimize allocation, enhance post-transplant survival benefit, decrease unequal transplant access, and optimize utilization of donated kidneys. Allocation of deceased donor kidneys is based on several criteria; however, the final decision to accept or reject the offered kidney is made by the potential recipient's transplant team (surgeon/nephrologist). Several considerations including assessment of the donor quality, the human leukocyte antigen (HLA) match between the donor and the recipient, numerous recipient factors, the geographical location of the recipient, and the organ all affect the decision to accept the organ or not for a particular recipient. This decision must be made quickly, often on the spot. Maximizing the benefit from this scarce resource raises difficult ethical issues. The philosophies of equity and utility are often competing. In this manuscript, we highlight a representative case that helps to focus on important issues for the pediatric nephrologist to consider while making the decision to accept a deceased donor kidney offer for a particular pediatric patient. PMID- 26130249 TI - YBYRA facilitates comparison of large phylogenetic trees. AB - BACKGROUND: The number and size of tree topologies that are being compared by phylogenetic systematists is increasing due to technological advancements in high throughput DNA sequencing. However, we still lack tools to facilitate comparison among phylogenetic trees with a large number of terminals. RESULTS: The "YBYRA" project integrates software solutions for data analysis in phylogenetics. It comprises tools for (1) topological distance calculation based on the number of shared splits or clades, (2) sensitivity analysis and automatic generation of sensitivity plots and (3) clade diagnoses based on different categories of synapomorphies. YBYRA also provides (4) an original framework to facilitate the search for potential rogue taxa based on how much they affect average matching split distances (using MSdist). CONCLUSIONS: YBYRA facilitates comparison of large phylogenetic trees and outperforms competing software in terms of usability and time efficiency, specially for large data sets. The programs that comprises this toolkit are written in Python, hence they do not require installation and have minimum dependencies. The entire project is available under an open-source licence at http://www.ib.usp.br/grant/anfibios/researchSoftware.html . PMID- 26130250 TI - Liver transplantation for hepatocellular carcinoma: outcomes and treatment options for recurrence. AB - Overall survival and recurrence rates after liver transplantation (LT) for hepatocellular carcinoma (HCC) vary, however observational data support the notion that patients with HCC have an overall worse long-term prognosis after LT compared to patients transplanted without HCC. Patient selection for LT in patients with HCC fluctuated as changes in the model for end-stage liver disease score was adjusted from 2002 to 2005. In the last decade, management of HCC patients on the waiting list has varied based on center experience. Since HCC patients have better access to the donor pool compared to non-HCC patients as evidenced by their lower dropout rate from the waiting list, living donation has been implemented in certain centers. Overall patient survival, recurrence free survival, and recurrence rates have been compared between living donor LT (LDLT) and deceased donor LT, with one meta-analysis reporting a lower disease free survival in LDLT, however overall patient survival and recurrence rates showed no difference at 1, 3 and 5 years. In patients exhibiting HCC recurrence, different modalities regarding immunosuppression and therapies have been evaluated. Currently there are no consensus treatment strategies regarding post-transplant HCC recurrence in patients not suitable for locoregional therapy, hence consideration of a mammalian target of rapamycin inhibitors with the addition of sorafenib might be a feasible option with close monitoring in clinical practice despite the notable toxicities. PMID- 26130251 TI - A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum alpha-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP. AB - In animal models of hepatocellular carcinoma (HCC), deficiency of S adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum alpha fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential. PMID- 26130252 TI - Dietary gamma-Tocopherol-Rich Mixture Inhibits Estrogen-Induced Mammary Tumorigenesis by Modulating Estrogen Metabolism, Antioxidant Response, and PPARgamma. AB - This study evaluated the anticancer activity and mechanism of action of a gamma tocopherol-rich tocopherol mixture, gamma-TmT, in two different animal models of estrogen-induced breast cancer. The chemopreventive effect of gamma-TmT at early (6 weeks), intermediate (18 weeks), and late (31 weeks) stages of mammary tumorigenesis was determined using the August-Copenhagen Irish rat model. Female rats receiving 17beta-estradiol (E2) implants were administered with different doses (0%, 0.05%, 0.1%, 0.3%, and 0.5%) of gamma-TmT diet. Treatment with 0.3% and 0.5% gamma-TmT decreased tumor volume and multiplicity. At 31 weeks, serum concentrations of E2 were significantly decreased by gamma-TmT. gamma-TmT preferentially induced expression of the E2-metabolizing enzyme CYP1A1, over CYP1B1 in the rat mammary tissues. Nrf2-dependent antioxidant response was stimulated by gamma-TmT, as evident from enhanced expression of its downstream targets, NQO1, GCLM, and HMOX1. Serum concentrations of the oxidative stress marker, 8-isoprostane, were also decreased in the gamma-TmT-treated groups. Treatment with gamma-TmT increased expression of PPARgamma and its downstream genes, PTEN and p27, whereas the cell proliferation marker, PCNA, was significantly reduced in gamma-TmT-treated mammary tumors. In an orthotopic model in which human MCF-7 breast cancer cells were injected into the mammary fat pad of immunodeficient mice, gamma-TmT inhibited E2-dependent tumor growth at all the doses tested. In conclusion, gamma-TmT reduced mammary tumor development, in part through decreased E2 availability and reduced oxidative stress in mammary tissues; gamma-TmT could thus be an effective agent for the prevention and treatment of E2-induced breast cancer. PMID- 26130253 TI - Assessment of Esophageal Adenocarcinoma Risk Using Somatic Chromosome Alterations in Longitudinal Samples in Barrett's Esophagus. AB - Cancers detected at a late stage are often refractory to treatments and ultimately lethal. Early detection can significantly increase survival probability, but attempts to reduce mortality by early detection have frequently increased overdiagnosis of indolent conditions that do not progress over a lifetime. Study designs that incorporate biomarker trajectories in time and space are needed to distinguish patients who progress to an early cancer from those who follow an indolent course. Esophageal adenocarcinoma is characterized by evolution of punctuated and catastrophic somatic chromosomal alterations and high levels of overall mutations but few recurrently mutated genes aside from TP53. Endoscopic surveillance of Barrett's esophagus for early cancer detection provides an opportunity for assessment of alterations for cancer risk in patients who progress to esophageal adenocarcinoma compared with nonprogressors. We investigated 1,272 longitudinally collected esophageal biopsies in a 248 Barrett's patient case-cohort study with 20,425 person-months of follow-up, including 79 who progressed to early-stage esophageal adenocarcinoma. Cancer progression risk was assessed for total chromosomal alterations, diversity, and chromosomal region-specific alterations measured with single-nucleotide polymorphism arrays in biopsies obtained over esophageal space and time. A model using 29 chromosomal features was developed for cancer risk prediction (area under receiver operator curve, 0.94). The model prediction performance was robust in two independent esophageal adenocarcinoma sets and outperformed TP53 mutation, flow cytometric DNA content, and histopathologic diagnosis of dysplasia. This study offers a strategy to reduce overdiagnosis in Barrett's esophagus and improve early detection of esophageal adenocarcinoma and potentially other cancers characterized by punctuated and catastrophic chromosomal evolution. PMID- 26130254 TI - Relative levels of let-7a, miR-17, miR-27b, miR-125a, miR-125b and miR-206 as potential molecular markers to evaluate grade, receptor status and molecular type in breast cancer. AB - MicroRNAs (miRNAs/miRs) are a class of short, single-stranded nucleic acids, which have been investigated as potential molecular markers for various types of cancer. The gold-standard and most sensitive method for comparing miRNA levels in cancer tissues is reverse transcription-quantitative polymerase chain reaction (RT-qPCR). This technique uses stably expressed genes for normalisation. The aim of the present study was to improve this model of analysis in the context of RT qPCR results. A total of six known miRNAs (let-7a, miR-17, miR-27b, miR-125a, miR 125b and miR-206), RNU6B RNA and five mRNAs [erb-b2 receptor tyrosine kinase 2 (ERBB2), hydroxymethylbilane synthase and polymerase (RNA) II (DNA directed) polypeptide A] were analysed pair-wise, in order to determine which biomarker pairs best correlated with the histological groups of 27 breast cancer samples. The lowest P-values and the highest area under the curve values in the receiver operating characteristic analysis were used to select the optimum ratios for discrimination among groups. Among the 21 pairs, miR-17/miR-27b and miR 125a/RNU6B best discriminated three groups of samples with different tumour grades (G classification). miR-125b/miR-206 best discriminated two groups of samples with different tumour sizes (pT), let-7a/RNU6B best discriminated two groups of samples with different lymph node status (pN), and let-7a/miR-125b best discriminated groups of samples with negative and positive oestrogen and progesterone receptor status. No pair of miRNAs was found to discriminate well between groups with either a negative or positive human epidermal growth factor receptor 2 (HER2) status. However, one miRNA/mRNA pair, miR-125a/ERBB2, discriminated HER2-negative from HER2-positive groups. The breast cancer samples investigated in the present study were grouped by immunohistological methods into three molecular classes: Luminal, HER2 positive and basal (L, H and B, respectively). In order to discern L from H and L from B, two miRNA pairs were selected: miR-125a/miR-125b and miR-125a/miR-206. In conclusion, the pair-wise method of RT-qPCR data analysis may be a reasonable alternative to the standard method of using stably expressed reference genes, such as RNU6B RNA, for normalisation. This method may increase the classification power of miRNA biomarkers in breast cancer diagnostics. PMID- 26130255 TI - Bortezomib Inhibits Osteoclastogenesis and Porphyromonas gingivalis Lipopolysaccharide-induced Alveolar Bone Resorption. AB - Healthy bone is maintained by the coordinated activities of osteoblast-mediated bone formation and osteoclast-dependent bone resorption. Pathologic conditions such as hormonal imbalance and inflammation cause increased osteoclastogenesis resulting in osteoporosis, rheumatoid arthritis, and periodontitis. Bortezomib is novel antimyeloma agent that has a direct beneficial effect on bone formation. However, the role of bortezomib in osteoclastogenesis and underlying mechanisms remains to be fully comprehended. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor kappaB ligand (RANKL) and lipopolysaccharide-dependent osteoclast differentiation. Interestingly, the bortezomib-mediated inhibition of osteoclastogenesis was transient, since the removal of bortezomib from culture completely restored osteoclast differentiation. Bortezomib impeded the induction and nuclear localization of nuclear factor of activated T cells, cytoplasmic 1 and reduced both macrophage colony-stimulating factor- and RANKL-induced extracellular-signal-regulated kinase (ERK) phosphorylation. In a mouse model of periodontitis, bortezomib prevented alveolar bone erosion induced by Porphyromonas gingivalis lipopolysaccharide. These data not only suggest a previously unappreciated mechanism by which bortezomib regulates bone resorption but also propose novel applications of bortezomib beyond its use as an antimyeloma agent. PMID- 26130256 TI - Nanoadhesion of Staphylococcus aureus onto Titanium Implant Surfaces. AB - Adhesion of bacteria to dental implant surfaces is the critical initial step in the process of biofilm colonization; however, the specific nanoadhesive interactions occurring during the first contact between bacterial cells and biomaterial substrates remain poorly understood. In this report, we utilize single-cell force spectroscopy to characterize the dynamics of the initial interaction between living Staphylococcus aureus cells and machined titanium surfaces at the nanoscale. Values for maximum adhesion force were found to increase from 0-s (-0.27 +/- 0.30 nN) to 60-s (-9.15 +/- 0.78 nN) surface delays, with similar results observed for total adhesion work (7.39 +/- 2.38 and 988.06 +/- 117.08 aJ, respectively). Single unbinding events observed at higher surface delays were modeled according to the wormlike chain model, obtaining molecular contour-length predictions of 314.06 +/- 9.27 nm. Average single-bond rupture forces of -0.95 +/- 0.04 nN were observed at increased contact times. Short- and long-range force components of bacterial adhesion were obtained by Poisson analysis of single unbinding event peaks, yielding values of -0.75 +/- 0.04 and 0.58 +/- 0.15 nN, respectively. Addition of 2-mg/mL chlorhexidine to the buffer solution resulted in the inhibition of specific adhesive events but an increased overall adhesion force and work. These results suggest that initial attachment of S. aureus to smooth titanium is mostly mediated by short-range attractive forces observed at higher surface delays. PMID- 26130257 TI - Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice. AB - Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/ )) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/ ) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp(-/-) mice. PMID- 26130258 TI - External Dentin Stimulation Induces ATP Release in Human Teeth. AB - ATP is involved in neurosensory processing, including nociceptive transduction. Thus, ATP signaling may participate in dentin hypersensitivity and dental pain. In this study, we investigated whether pannexins, which can form mechanosensitive ATP-permeable channels, are present in human dental pulp. We also assessed the existence and functional activity of ecto-ATPase for extracellular ATP degradation. We further tested if ATP is released from dental pulp upon dentin mechanical or thermal stimulation that induces dentin hypersensitivity and dental pain and if pannexin or pannexin/gap junction channel blockers reduce stimulation dependent ATP release. Using immunofluorescence staining, we demonstrated immunoreactivity of pannexin 1 and 2 in odontoblasts and their processes extending into the dentin tubules. Using enzymatic histochemistry staining, we also demonstrated functional ecto-ATPase activity within the odontoblast layer, subodontoblast layer, dental pulp nerve bundles, and blood vessels. Using an ATP bioluminescence assay, we found that mechanical or cold stimulation to the exposed dentin induced ATP release in an in vitro human tooth perfusion model. We further demonstrated that blocking pannexin/gap junction channels with probenecid or carbenoxolone significantly reduced external dentin stimulation-induced ATP release. Our results provide evidence for the existence of functional machinery required for ATP release and degradation in human dental pulp and that pannexin channels are involved in external dentin stimulation-induced ATP release. These findings support a plausible role for ATP signaling in dentin hypersensitivity and dental pain. PMID- 26130259 TI - Soft Tissue Alterations in Esthetic Postextraction Sites: A 3-Dimensional Analysis. AB - Dimensional alterations of the facial soft and bone tissues following tooth extraction in the esthetic zone play an essential role to achieve successful outcomes in implant therapy. This prospective study is the first to investigate the interplay between the soft tissue dimensions and the underlying bone anatomy during an 8-wk healing period. The analysis is based on sequential 3-dimensional digital surface model superimpositions of the soft and bone tissues using digital impressions and cone beam computed tomography during an 8-wk healing period. Soft tissue thickness in thin and thick bone phenotypes at extraction was similar, averaging 0.7 mm and 0.8 mm, respectively. Interestingly, thin bone phenotypes revealed a 7-fold increase in soft tissue thickness after an 8-wk healing period, whereas in thick bone phenotypes, the soft tissue dimensions remained unchanged. The observed spontaneous soft tissue thickening in thin bone phenotypes resulted in a vertical soft tissue loss of only 1.6 mm, which concealed the underlying vertical bone resorption of 7.5 mm. Because of spontaneous soft tissue thickening, no significant differences were detected in the total tissue loss between thin and thick bone phenotypes at 2, 4, 6, and 8 wk. More than 51% of these dimensional alterations occurred within 2 wk of healing. Even though the observed spontaneous soft tissue thickening in thin bone phenotypes following tooth extraction conceals the pronounced underlying bone resorption pattern by masking the true bone deficiency, spontaneous soft tissue thickening offers advantages for subsequent bone regeneration and implant therapies in sites with high esthetic demand (Clinicaltrials.gov NCT02403700). PMID- 26130260 TI - Orthodontic Force Induces Systemic Inflammatory Monocyte Responses. AB - Periodontal inflammation and alveolar bone remodeling during orthodontic tooth movement are considered regional reactions. However, how systemic immune responses are involved in this regional reaction remains unclear. In this study, we explored the systemic effects of orthodontic force by focusing on the mononuclear phagocyte system. Flow cytometric analysis showed that the percentage of inflammatory monocytes, in peripheral blood and in the monocyte reservoir spleen, decreased on days 1 and 3 and then recovered on day 7 after force application. Along with the systemic decrease of inflammatory monocyte percentage, the number of tartrate-resistant acid phosphatase-positive osteoclasts increased in the compression side of the periodontal tissue during orthodontic tooth movement. Systemic transfusion of enhanced green fluorescent protein-labeled inflammatory monocytes showed recruitment of these monocytes to the orthodontic force compression side of periodontal tissues. These monocytes were colocalized with tartrate-resistant acid phosphatase-positive osteoclasts. In vivo and in vitro experiments showed that orthodontic force could upregulate the expression of pivotal monocyte chemokine monocyte chemotactic protein 1 in periodontal tissues or cultured periodontal ligament cells, which may contribute to monocyte recruitment to regional sites. These data suggest that orthodontic force induces systemic immune responses related to inflammatory monocytes and that systemic inflammatory monocytes can be recruited to periodontal tissues by orthodontic force stimulus. PMID- 26130261 TI - Oral Health Inequalities: Relationships between Environmental and Individual Factors. AB - Recent research has emphasized the relationships between environmental and individual factors that may influence population oral health and lead to health inequalities. However, little is known about the effect of interactions between environmental and individual factors on inequalities in clinical (e.g., decayed teeth) and subjective oral health outcomes (e.g., oral health-related quality of life [OHQoL]). This cohort study aimed to explore the direct and mediated longitudinal interrelationships between key environmental and individual factors on clinical and subjective oral health outcomes in adults. Self-reported measures of OHQoL and individual (sense of coherence [SOC], social support, stress, oral health beliefs, dental behaviors, and subjective socioeconomic status [SES]) and environmental factors (SES and social network) were collected at baseline and 3 mo follow-up, together with a baseline clinical examination of 495 adult employees of an automobile parts manufacturer in India. Lagged structural equation modeling was guided by the adapted Wilson and Cleary/Brunner and Marmot model linking clinical, individual, and environmental variables to quality of life. The study provides tentative evidence that SES may influence levels of resources such as social support and SOC, which mediate stress and in turn may influence subjective oral health outcomes. Accordingly, the present findings and the adapted Wilson and Cleary/Brunner and Marmot model on which they are predicted provide support for the psychosocial pathway being key in the SES-oral health relationship. The pathways through which environmental factors interact with individual factors to impact subjective oral health outcomes identified here may bring opportunities for more targeted oral health promotion strategies. PMID- 26130262 TI - Stress echocardiography in paediatric cardiology. AB - Stress echocardiography is a well-established technique in adult cardiology and is mainly used for assessing regional myocardial function in patients with known or suspected coronary artery disease (CAD). Apart from detecting ischaemia, stress echocardiography has found its place in the assessment of the haemodynamic significance of valve disease, particularly in selected patients with aortic stenosis and mitral regurgitation. Also in the paediatric population, stress imaging is most commonly used for the detection of ischaemia in patients with CADs such as post heart transplantation, Kawasaki Disease, and abnormal origin of coronary arteries. Other paediatric indications include the haemodynamic and myocardial response in patients with different types of congenital heart disease, the early detection of myocardial dysfunction in specific populations such as patients after anthracycline exposure, and the evaluation of pulmonary artery pressures and the right ventricular functional response. Techniques have evolved over time and in different paediatric echocardiographic laboratories, exercise stress echocardiography is replacing dobutamine stress echocardiography in older children. Moreover, integrating tissue Doppler and strain technology with stress imaging allows a more quantitative analysis of regional and global systolic and diastolic function. Current clinical applications mainly include patients after transplant, suspected CAD, and hypertrophic cardiomyopathy. PMID- 26130263 TI - Signatures of positive selection in East African Shorthorn Zebu: A genome-wide single nucleotide polymorphism analysis. AB - The small East African Shorthorn Zebu (EASZ) is the main indigenous cattle across East Africa. A recent genome wide SNP analysis revealed an ancient stable African taurine x Asian zebu admixture. Here, we assess the presence of candidate signatures of positive selection in their genome, with the aim to provide qualitative insights about the corresponding selective pressures. Four hundred and twenty-five EASZ and four reference populations (Holstein-Friesian, Jersey, N'Dama and Nellore) were analysed using 46,171 SNPs covering all autosomes and the X chromosome. Following FST and two extended haplotype homozygosity-based (iHS and Rsb) analyses 24 candidate genome regions within 14 autosomes and the X chromosome were revealed, in which 18 and 4 were previously identified in tropical-adapted and commercial breeds, respectively. These regions overlap with 340 bovine QTL. They include 409 annotated genes, in which 37 were considered as candidates. These genes are involved in various biological pathways (e.g. immunity, reproduction, development and heat tolerance). Our results support that different selection pressures (e.g. environmental constraints, human selection, genome admixture constrains) have shaped the genome of EASZ. We argue that these candidate regions represent genome landmarks to be maintained in breeding programs aiming to improve sustainable livestock productivity in the tropics. PMID- 26130264 TI - Surgery for epilepsy. AB - BACKGROUND: Focal epilepsies are caused by a malfunction of nerve cells localised in one part of one cerebral hemisphere. In studies, estimates of the number of individuals with focal epilepsy who do not become seizure-free despite optimal drug therapy vary according to the age of the participants and which focal epilepsies are included, but have been reported as at least 20% and in some studies up to 70%. If the epileptogenic zone can be located surgical resection offers the chance of a cure with a corresponding increase in quality of life. OBJECTIVES: The primary objective is to assess the overall outcome of epilepsy surgery according to evidence from randomised controlled trials.The secondary objectives are to assess the overall outcome of epilepsy surgery according to non randomised evidence and to identify the factors that correlate to remission of seizures postoperatively. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 6), MEDLINE (Ovid) (2001 to 4 July 2013), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for relevant trials up to 4 July 2013. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs), cohort studies or case series, with either a prospective and/or retrospective design, including at least 30 participants, a well-defined population (age, sex, seizure type/frequency, duration of epilepsy, aetiology, magnetic resonance imaging (MRI) diagnosis, surgical findings), an MRI performed in at least 90% of cases and an expected duration of follow-up of at least one year, and reporting an outcome relating to postoperative seizure control. DATA COLLECTION AND ANALYSIS: Three groups of two review authors independently screened all references for eligibility, assessed study quality and risk of bias, and extracted data. Outcomes were proportion of participants achieving a good outcome according to the presence or absence of each prognostic factor of interest. We intended to combine data with risk ratios (RR) and 95% confidence intervals. MAIN RESULTS: We identified 177 studies (16,253 participants) investigating the outcome of surgery for epilepsy. Four studies were RCTs (including one that randomised participants to surgery or medical treatment). The risk of bias in the RCTs was unclear or high, limiting our confidence in the evidence that addressed the primary review objective. Most of the remaining 173 non-randomised studies had a retrospective design; they were of variable size, were conducted in a range of countries, recruited a wide demographic range of participants, used a wide range of surgical techniques and used different scales used to measure outcomes. We performed quality assessment using the Effective Public Health Practice Project (EPHPP) tool and determined that most studies provided moderate or weak evidence. For 29 studies reporting multivariate analyses we used the Quality in Prognostic Studies (QUIPS) tool and determined that very few studies were at low risk of bias across the domains.In terms of freedom from seizures, one RCT found surgery to be superior to medical treatment, two RCTs found no statistically significant difference between anterior temporal lobectomy (ATL) with or without corpus callosotomy or between 2.5 cm or 3.5 cm ATL resection, and one RCT found total hippocampectomy to be superior to partial hippocampectomy. We judged the evidence from the four RCTs to be of moderate to very low quality due to the lack of information reported about the randomised trial design and the restricted study populations.Of the 16,253 participants included in this review, 10,518 (65%) achieved a good outcome from surgery; this ranged across studies from 13.5% to 92.5%. Overall, we found the quality of data in relation to the recording of adverse events to be very poor.In total, 118 studies examined between one and eight prognostic factors in univariate analysis. We found the following prognostic factors to be associated with a better post-surgical seizure outcome: an abnormal pre-operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre operative MRI and electroencephalography (EEG), history of febrile seizures, absence of focal cortical dysplasia/malformation of cortical development, presence of tumour, right-sided resection and presence of unilateral interictal spikes. We found no evidence that history of head injury, presence of encephalomalacia, presence of vascular malformation or presence of postoperative discharges were prognostic factors of outcome. We observed variability between studies for many of our analyses, likely due to the small study sizes with unbalanced group sizes, variation in the definition of seizure outcome, definition of the prognostic factor and the influence of the site of surgery, all of which we observed to be related to postoperative seizure outcome. Twenty-nine studies reported multivariable models of prognostic factors and the direction of association of factors with outcome was generally the same as found in the univariate analyses. However, due to the different multivariable analysis approaches and selective reporting of results, meaningful comparison of multivariate analysis with univariate meta-analysis is difficult. AUTHORS' CONCLUSIONS: The study design issues and limited information presented in the included studies mean that our results provide limited evidence to aid patient selection for surgery and prediction of likely surgical outcome. Future research should be of high quality, have a prospective design, be appropriately powered and focus on specific issues related to diagnostic tools, the site-specific surgical approach and other issues such as the extent of resection. Prognostic factors related to the outcome of surgery should be investigated via multivariable statistical regression modelling, where variables are selected for modelling according to clinical relevance and all numerical results of the prognostic models are fully reported. Protocols should include pre- and postoperative measures of speech and language function, cognition and social functioning along with a mental state assessment. Journal editors should not accept papers where adverse events from a medical intervention are not recorded. Improvements in the development of cancer care over the past three to four decades have been achieved by answering well-defined questions through the conduct of focused RCTs in a step-wise fashion. The same approach to surgery for epilepsy is required. PMID- 26130265 TI - Unraveling the mechanisms of action of lactoferrin-derived antihypertensive peptides: ACE inhibition and beyond. AB - Hypertension is one of the most important causes of cardiovascular and renal morbidity and mortality, and it represents a serious health problem in Western countries. Over the last few decades scientific interest in food-derived antihypertensive peptides has grown as an alternative to drugs in the control of systemic blood pressure. Most of these peptides target the angiotensin I converting enzyme (ACE) but emerging evidence points to other antihypertensive mechanisms beyond ACE inhibition. The milk protein lactoferrin (LF) is a good source of orally active antihypertensive peptides the characterization of which, including ex vivo functional assays and in vivo approaches, shows that they might act on several molecular targets. This review summarizes the mechanisms of action underlying the blood pressure-lowering effects of LF-derived peptides, focusing on their interaction with different components of the renin-angiotensin (RAS) and endothelin (ET) systems. The ability of LF-derived peptides to modify the expression of genes encoding proteins involved in the nitric oxide (NO) pathway and prostaglandin synthesis is also described. PMID- 26130266 TI - Carbon Monoxide Addition to Ruthenium-Dithiolene Complex and Polysiloxane Hybrid Film Formation. AB - The addition of carbon monoxide to the ruthenium center of [(eta(6) -C6 Me6 )Ru(S2 C6 H4 )] (1) has been investigated. [(eta(6) -C6 Me6 )Ru(CO)(S2 C6 H4 )] (2) was obtained by the addition of CO gas to the ruthenium center of 1 in both solution and solid states. 1 was reproduced by treating 2 with an oxidant. A 1/polysiloxane self-standing hybrid film was also prepared and showed a dramatic color change upon transformation of 1 to 2 in polysiloxane hybrid film. PMID- 26130267 TI - Diverse Profiles of N-acyl Homoserine L-Lactones, Biofilm, Virulence Genes and Integrons in Food-Borne Aeromonas Isolates. AB - Aeromonas are regarded as opportunistic as well as primary pathogens of humans and fish, and are associated with gastroenteritis and septicemia in humans. Production of N-acyl-homoserine lactone (AHL) signal molecules and biofilm was determined in 22 Aeromonas isolates, from different food products in India, using thin-layer chromatography (TLC) analysis and microtiter-plate assay, respectively. Overall, highly heterogeneous patterns of AHL production were observed, with the production of N-butanoyl homoserine lactone (C4-HSL) and N hexanoyl homoserine lactone (C6-HSL) by the majority (81.8%) of Aeromonas food isolates. Moreover, putative N-pentanoyl homoserine lactone (C5-HSL), N-heptanoyl homoserine lactone (C7-HSL), and N-octanoyl homoserine lactone (C8-HSL) were produced by 72.7%, 27.3%, and 9.1% of isolates, respectively. This is the 1st report of production of C7-HSL by Aeromonas species. Aeromonas food isolates were highly variable in their biofilm forming abilities with majority of them as weak biofilm producers in 2 different media, TSB and M9 minimal medium supplemented with 0.4% glucose. The genes encoding for putative virulence factors, glycerophospholipid cholesterol acyltransferase (gcat), heat-labile cytotonic enterotoxin (alt), heat-stable cytotonic enterotoxin (ast), serine protease (ser), polar flagella (fla), and lateral flagella (lafA) were present in 95.5%, 59.1%, 22.7%, 81.8%, 77.3%, and 22.7% of the strains, respectively. Class 1 integrons (100 to 3000 bp) were found in 68.2% of food isolates; whereas, 50% isolates contained class 2 integrons (150 to 1600 bp). This study provides a baseline data on the diversity of AHLs, biofilm forming ability and presence of virulence genes and integrons in Aeromonas food isolates from India. PMID- 26130268 TI - Prognostic value of the lymph node ratio in breast cancer subtypes. AB - BACKGROUND: Several studies indicate that lymph node (LN) ratio (LNR) is more predictive than the traditional LN-positive stratification (pNs). We assessed whether LNR can provide additional prognostic information on node-positive breast cancer patients, particularly with breast cancer subtypes (BCS). METHODS: We retrospectively reviewed the medical records of 2,049 patients with primary breast cancer treated between January 2006 and December 2011 and identified 511 subjects with positive axillary LN. Clinicopathological findings, types of treatment, and the 5-year overall survival (OS) were included. RESULTS: The results of multivariate analysis of the cohort showed that the correlations of pNs and LNR in regard to OS were P < .001 and P < .001, respectively, with adjustment for tumor characteristics and treatment factors. Moreover, our data revealed that LNR was more predictive in luminal A, luminal B, and luminal human epidermal growth factor receptor 2 in a comparison of pNs and LNR with regard to OS among BCS. CONCLUSION: LNR and pNs are important prognostic factors with regard to OS for patients with node-positive breast cancer, but LNR has a more correlated value in BCS. PMID- 26130269 TI - Comparison between Roux-en-Y patients with and without gastrectomy during endoscopic retrograde cholangiopancreatography using a short double-balloon enteroscope. PMID- 26130270 TI - 10-Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+) Dragmacidin D. AB - The asymmetric synthesis of dragmacidin D (1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2 symmetric tetramine and lithium N-(trimethylsilyl)-tert-butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6''' position, which is consistent with other members of the dragmacidin family of natural products. PMID- 26130271 TI - Highly homologous proteins exert opposite biological activities by using different interaction interfaces. AB - We present a possible molecular basis for the opposite activity of two homologues proteins that bind similar ligands and show that this is achieved by fine-tuning of the interaction interface. The highly homologous ASPP proteins have opposite roles in regulating apoptosis: ASPP2 induces apoptosis while iASPP inhibits it. The ASPP proteins are regulated by an autoinhibitory interaction between their Ank-SH3 and Pro domains. We performed a detailed biophysical and molecular study of the Pro - Ank-SH3 interaction in iASPP and compared it to the interaction in ASPP2. We found that iASPP Pro is disordered and that the interaction sites are entirely different: iASPP Ank-SH3 binds iASPP Pro via its fourth Ank repeat and RT loop while ASPP2 Ank-SH3 binds ASPP2 Pro via its first Ank repeat and the n src loop. It is possible that by using different moieties in the same interface, the proteins can have distinct and specific interactions resulting in differential regulation and ultimately different biological activities. PMID- 26130272 TI - Patchable, flexible heat-sensing hybrid ionic gate nanochannel modified with a wax-composite. AB - Heat-driven ionic gate nanochannels have been recently demonstrated, which exploit temperature-responsive polymer brushes based on wettability. These heat sensing artificial nanochannels operate in a broad temperature-response boundary and fixed liquid cell environment, thereby experiencing limited system operation in the flat and solid state. Here we have developed a patchable and flexible heat sensing artificial ionic gate nanochannel, which can operate in the range of the human body temperature. A wax-elastic copolymer, coated onto a commercial nanopore membrane by a controlled-vacuum filtration method, was used for the construction of temperature-responsive nanopores. The robust and flexible nanochannel heat sensor, which is combined with an agarose gel electrolyte, can sustain reversible thermo-responsive ionic gating based on the volumetric work of the wax-composite layers in a selective temperature range. The ionic current is also effectively distinguished in the patchable bandage-type nanochannel for human heat-sensing. PMID- 26130273 TI - Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease. AB - Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD. PMID- 26130274 TI - The comparative effectiveness of biologics among older adults and disabled rheumatoid arthritis patients in the Medicare population. AB - AIMS: Older and disabled rheumatoid arthritis (RA) patients are often not present in large numbers in clinical trials or registries. A novel, claims-based clinical effectiveness algorithm provides the potential to compare the effectiveness of different biologics among this population using large administrative databases. METHOD: Using Medicare 2006-2010 data for 100% of patients with RA, we identified biologic naive users of abatacept, adalimumab, etanercept and infliximab, defined as no biologic use during the 12 months before the biologic initiation. The effectiveness was evaluated at 365 days after biologic initiation, determined using a validated claims-based algorithm. We compared the proportion meeting effectiveness criteria for each biologic using robust Poisson regression to compute risk ratios (RRs) adjusted for potential confounders. One year cost per effectively treated patient was calculated by different biologics. RESULTS: The study included biologic naive users of abatacept (n = 2129), adalimumab (n = 2944), etanercept (n = 3517) and infliximab (n = 5654). The algorithm classified the medications as 26% effective for abatacept, 24% for adalimumab, 28% for etanercept and 23% for infliximab, indicating comparable effectiveness. However, after adjustment and compared with infliximab, the RRs for effectiveness were 1.17 (95% CI 1.06, 1.30) for abatacept, 1.11 (95% CI 1.02, 1.23) for adalimumab and 1.27 (95% CI 1.17, 1.39) for etanercept. Older patients had a higher effectiveness than patients who were disabled (RR = 1.18, 95% CI 1.08, 1.28). Infliximab had highest cost per effectively treated patient. CONCLUSION: Abatacept, adalimumab and etanercept are more effective than infliximab among RA patients initiating biologics. Effectiveness was significantly higher among older patients compared with disabled RA Medicare patients. PMID- 26130276 TI - Primary modular total knee replacement in severe and unstable osteoarthritis. Predictive factors for failure. AB - PURPOSE: Severe cases of osteoarthritis with ligamentous instability require the use of a modular knee arthoplasty. To assess the survival, the complications, the clinical, radiological and functional outcomes, and the quality of life of those patients in whom a Optetrak Condylar Constrained Knee (CCK) had been implanted as a primary implant. To study how the pre-operative conditions (deformity, age, sex ...) and the characteristics of the arthroplasty (stems, supplements, constrained component ...) could change the survival or the clinical outcomes of the implants. METHODS: We performed an observational retrospective study of 105 CCKs implanted between 1999 and 2005. The mean follow-up was nine years (7, 13). Mean age was 70.5 years. The mortality was 6.9 %. There were 9.3 % of the patients lost during the follow-up. We studied all the medical files of the patients in order to assess the pre-operative, surgical and postoperative conditions. We used the Knee Society Score (KSS), both clinical and functional, to study the functional and clinical situation. We analysed the X-ray using the Knee Society roentgenographic evaluation. The quality of life was studied using the Oxford Knee Score (OKS). Then in order to find predictor conditions, we made statistical multivariable predictive studies attending to the preoperative factors and to the arthroplasty conditions to compare both outcomes and survival (Kaplan-Meier groups curves and Cox Multivariable Models [hazard ratio]). Processing and data analysis was performed using SPSS 15.0. RESULTS: The outcomes did not show differences between all the groups. While the mean result of the clinical KSS was 75.8, the mean functional KSS was 73.1. We did not find a condition associated with worst results of the knees (p > 0.05). The KSS obtained was excellent or good in 74.9 %. The global survival at 24 months was 93.8 % and at 96 months was 90.1 %. There were some conditions associated with poorest survival of the arthroplasties: patients younger than 70 years old, tibial tuberosity osteotomy, use of long stems and new surgery two months after arthoplasty (p < 0.05). The 11.1 % of the arthroplasties required more surgeries (3.3 % were soft tissue surgeries and 7.8 % were revisions). The mean OKS obtained was 34.78. Satisfaction was obtained by 86.2 % of the patients. CONCLUSIONS: All severe and unstable knees obtained similar and overall excellent-good outcomes and survival using the Optetrak CCK. Although we found that there are some factors that could change the survival of the total knee replacement, these did not change the outcomes. PMID- 26130277 TI - Unicompartmental knee arthroplasty is effective: ten year results. AB - PURPOSE: Unicompartmental knee arthroplasty (UKA) presents low morbidity and complication risk and provides excellent outcomes and fast recovery. Despite these facts, knee-replacement registries have shown high failure rates for UKA, especially when compared with traditional TKA. The purpose of this study was therefore to report outcomes, complications, and ten year survivorship rate of medial ZUK unicompartmental knee prosthesis. METHODS: We retrospectively analysed 136 medial UKAs in 124 patients, with a maximum follow-up of ten years. Patients were assessed through the International Knee Society (IKS) scores and range of motion (ROM). A complete X-ray study was performed in all patients. Limb alignment was assessed by measuring the femorotibial mechanical alignment. At surgery, bone resections were performed according to proximal tibial epiphyseal axis. RESULTS: Mean IKS knee score improved from 45.7 (range 35-63) points preoperatively to 87.2 (range 71-100) points at the latest follow-up. Mean IKS function score improved from 50.9 (range 40-70) points to 89.1 (range 75-100) points (p < 0.05). Mean ROM increased from 106.1 degrees (range 98-123 degrees ) to 128.6 degrees (range 116-139 degrees ) (p < 0.01). Four cases (2.9 %) were revised due to failure for any cause, so that survivorship was 97.1 % at the latest follow-up. CONCLUSIONS: This study demonstrates excellent outcomes and survivorship for the ZUK unicompartmental knee prosthesis. Based on our findings, we believe that the ZUK prosthesis offers an effective and durable solution for treating medial degeneration of the knee. Level of Evidence IV - Retrospective case series study. PMID- 26130278 TI - A novel patient-specific navigational template for anatomical reconstruction of the lateral ankle ligaments. AB - PURPOSE: We discuss the clinical effects of anatomical reconstruction of the lateral ankle ligaments to treat chronic lateral ankle instability (CAI) by creating fibular channels with a patient-specific navigational template. METHODS: From August 2010 to February 2014, 15 patients presenting with CAI were treated by creating fibular channels with a patient-specific navigational template for anatomical reconstruction of the lateral ankle ligaments. RESULTS: All patients were followed up for nine to 24 months postoperatively (15 months on average); no recurrent CAI was found. Pre- and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) scores for patients in the calcaneofibular ligament (CFL) plus anterior talofibular ligament (ATFL) repair group were 48.3 +/- 5.1 and 88.1 +/- 6.7) respectively. The difference (average 39.8) showed high statistical significance (P < 0.001). Pre- and postoperative scores in the ATFL group were 50.4 +/- 6.2 and 90.3 +/- 7.8, respectively. The difference (average 39.9) showed high statistical significance (P < 0.001). Regarding the Good score, 14 patients were rated as "excellent and one as good (good = 100 %). No severe complications were found in the patients in this group. CONCLUSIONS: We studied and successfully built a digital navigation template for creating fibular channels to anatomically reconstruct the lateral ankle ligament. By using the template, fibular channels could be built, and lateral ligaments could be anatomically reconstructed individually, easily and safely, which largely facilitates the treatment of CAI. PMID- 26130279 TI - Complications following conversion of a hip hemiarthroplasty to a total hip arthroplasty. AB - PURPOSE: Conversion of hip hemiarthroplasty to total hip arthroplasty (CTHA) is a complication-prone procedure with high dislocation rates and early component loosening. The purpose of this study was to evaluate the complications of CTHA performed using contemporary implants. METHODS: Forty-six patients who had CTHA were retrospectively matched to a control group of 46 patients who had a first time THA revision. The mean follow-up was 47 (range 6-149) and 23 (range 6-139) months for CTHA and control groups, respectively. Radiographs taken at the last follow-up visit were evaluated for signs of loosening or other modes of failure. Clinical outcome was evaluated with the Harris Hip Score (HHS). RESULTS: Complications occurred in five patients (10.9 %) in the CTHA group, and all required repeat revision. Two patients (4.3 %) were revised due to recurrent dislocation. The other re-revisions were done for acetabular or femoral component loosening and deep infection. In the control group, complications occurred in six patients (13.0 %), and three (6.5 %) were revised with a constrained liner due to recurrent dislocations. CONCLUSIONS: Dislocation rates and re-revision for CTHA were not significantly different than those of first-time THA revision when using contemporary revision implants. PMID- 26130280 TI - Functional implications of femoral offset following hemiarthroplasty for displaced femoral neck fracture. AB - PURPOSE: Inadequate reconstruction of femoral offset after total hip arthroplasty (THA) is associated with unfavourable outcomes, but its importance following hemiarthroplasty for displaced femoral neck fracture is unknown. METHODS: Our study examined the correlation between reconstructed femoral offset and functional outcome 12 months after post traumatic hemiarthroplasty in 126 prospectively enrolled elderly patients. Rotation-corrected femoral offset (FORC), relative femoral offset (FORL) and contralateral femoral offset (FOC) were measured on anteroposterior radiographs. The Harris Hip Score (HHS) was the primary outcome measure; the timed up and go (TUG) test and Lawton instrumental activities of daily living (IADL) score were secondary outcomes. Correlations were sought using the Spearman correlation coefficient (r). Sample size was calculated using an Altman nomogram, with the power set at 80 %, the significance level of 0.05 and a standardised difference of 0.75. RESULTS: The mean reconstructed FORC was 41 mm (17-67 mm) and showed a linear relationship and excellent correlation with the FOC. At 12 months, we found a significant positive correlation between FORC and HHS (r = 0.303, p = 0.025) and IADL (r = 0.325, p = 0.013), but not TUG (r = -0.026, p = 0.863). These findings were confirmed by bivariate and multivariate correlation between FORL and functional outcome parameters. CONCLUSIONS: We found a clinically relevant relationship between femoral offset and functional outcome after hemiarthroplasty in elderly patients, comparable with that of THA, for treating osteoarthritis. PMID- 26130281 TI - Ligament, nerve, and blood vessel anatomy of the lateral zone of the lumbar intervertebral foramina. AB - PURPOSE: To provide an anatomical basis for intrusive treatment using an approach through the lateral zones of the lumbar intervertebral foramina (LIF), especially for acupotomology lysis, percutaneous transforaminal endoscopy, and lumbar nerve root block. METHODS: Blood vessels, ligaments, nerves, and adjacent structures of ten cadavers were exposed through the L1-2 to L5-S1 intervertebral foramina and examined. RESULTS: The lateral zones of the LIF were almost filled by ligaments, nerves, and blood vessels, which were separated into compartments by superior/inferior transforaminal ligaments and corporotransverse superior/inferior ligaments. Two zones relatively lacking in blood vessels and nerves (triangular working zones) were found beside the lamina of the vertebral arch and on the root of the transverse processus. Both the ascending lumbar vein and branches of the intervetebral vein were observed in 12 Kambin's triangles, and in only seven Kambin's triangles were without any veins. CONCLUSIONS: Nerves and blood vessels are fixed and protected by transforaminal ligaments and/or corporotransverse ligaments. It is necessary to distinguish the ligaments from nerves using transforaminal endoscopy so that the ligaments can be cut without damaging nerves. Care needs to be taken in intrusive operations because of the veins running through Kambin's triangle. We recommend injecting into the lamina of the vertebral arch and the midpoint between the adjacent roots of the transverse processus when administering nerve root block. Blind percutaneous incision and acupotomology lysis is dangerous in the lateral zones of the LIF, as they are filled with nerves and blood vessels. PMID- 26130282 TI - Modified head-neck offset for diagnosing anterior femoro-acetabular impingement. AB - PURPOSE: The head-neck offset described by Eijer et al. (eHNO), which is used to diagnose anterior femoro-acetabular impingement (FAI), can be difficult to measure. The aim of this study was to verify if a modified head-neck offset (mHNO) provides more accurate and reproducible values than those of the eHNO. METHODS: The eHNO, mHNO, cephalic radius and alpha angle were measured on frog leg radiographs of a group of patients with FAI and a control group (T); three independent reviewers measured the 50 hips in each group twice. The comparison of the two HNOs focused on reproducibility (intraclass correlation coefficient), validity (correlation with alpha angle), practical utility (difference between means in the FAI and control groups) and accuracy of the diagnostic thresholds. RESULTS: The mHNO had better reproducibility (p < 0.05) within and between observers in all study subjects than that of the eHNO (0.938 and 0.979 vs 0.881 and 0.904). The correlation with the alpha angle was also better (p < 0.05) for the mHNO than that for the eHNO. The diagnostic performances of the mHNO and mAOR thresholds were higher than those of the eHNO, eAOR and alpha angle. CONCLUSIONS: The new HNO is easier to measure, more reproducible and more accurate. A modified HNO <5 mm and a modified AOR <0.100 on the frog-leg view argued in favour of a pathological cam-type head-neck junction. PMID- 26130283 TI - Gluteal muscle fibrosis with abduction contracture of the hip. AB - PURPOSE: Gluteal muscle fibrosis with hip contracture is a rare condition and causes major disability; literature reports are sparse. The aim of this study is to present, for the first time in Iraq and the region, a case series of gluteal fibrosis and the results of surgical treatment. METHODS: Seven children--six boys and one girl--diagnosed as having gluteal muscle fibrosis with hip contracture, were investigated and treated by open surgical release of fibrotic bands and physiotherapy. RESULTS: All patients improved dramatically over the subsequent weeks, and were able to sit and squat in the normal position. CONCLUSIONS: Gluteal muscle fibrosis with hip contracture is present in Iraq and more awareness is needed for early diagnosis. Surgical treatment provided excellent results. More studies are needed to delineate the aetiology of the condition. PMID- 26130284 TI - Computer navigation for revision of unicompartmental knee replacements to total knee replacements: the results of a case-control study of forty six knees comparing computer navigated and conventional surgery. AB - PURPOSE: The revision of unicompartmental knee replacements (UKRs) to total knee replacements (TKRs) using computer navigation is a little-known technique. The principal objective of this study was to analyse the radiological position of implants in revision of UKR to TKR comparing the results of surgery aided by computer navigation (CAS) with conventional surgery (CS). Our hypothesis was that computer navigation would improve the position of the implants. METHODS: This is a retrospective single surgeon series. Forty-six patients (46 knees) with an average age 73 +/- eight years (53-93) between January 1995 and December 2014 were included. The two groups were made up of 23 patients each and are comparable in terms of age, sex, side of surgery, age of the UKR, cause of failure and HKA angle before surgery. All patients were reviewed by two independent observers. RESULTS: In the CAS group, the average hip-knee-ankle (HKA) angle was 179.2 +/- 2.2 degrees (175-184 degrees ). The average medial tibial mechanical angle (TMA) was 88.4 +/- 1.6 degrees (84-90 degrees ) and the medial femoral mechanical angle (FMA) was 91 +/- 2 degrees (87- 94 degrees ). The tibial slope was 88.7 +/ 1.1 degrees (87-90 degrees ). In the CS group, the average HKA angle was 179.9 +/- 1.9 degrees (175-183 degrees ), the TMA was on average 89.1 +/- 1.3 degrees (87-93 degrees ) and the FMA was 90.6 +/- 1.5 degrees (87-93 degrees ). The tibial slope was 87.8 +/- 4.9 degrees (85-95 degrees ). There was no statistically significant difference between the two groups on any of the radiological parameters studied. CONCLUSIONS: Our radiological target of a post operative HKA angle of 180 +/- 3 degrees was obtained in 87.5% of cases in the CS group and 92.4% of cases in the CAS group. This slight difference in favour of the computer-assisted group was not statistically significant, and we cannot therefore confirm our initial hypothesis, at least in the hands of an experienced surgeon. However, the quality of the results in the CAS group suggest that this technique could provide precious assistance to less experienced surgeons performing this surgery. PMID- 26130285 TI - Is the use of thin, highly cross-linked polyethylene liners safe in total hip arthroplasty? AB - PURPOSE: Due to the high number of total hip arthroplasties (THA) revised due to instability, the use of large femoral heads to reduce instability is justifiable. It is critical to determine whether or not large femoral heads used in conjunction with thin polyethylene liners lead to increased wear rates, which can lead to osteolysis. Therefore, by using validated wear-analysis software, we evaluated linear wear rates in a consecutive cohort of patients who underwent primary THA with thin polyethylene liners. METHODS: All patients were selected from a consecutive, prospectively collected database of 241 THAs performed at a single institution by two fellowship-trained joint-reconstruction surgeons between July 2007 and June 2011. These patients were 1:1 matched to a cohort of patients who had conventional-thickness polyethylene liners. RESULTS: No significant differences were observed between linear wear rates of thin or conventional-thickness liners. The Kaplan-Meier survivorship for both cohorts was 100 %, and no cases of polyethylene fracture were observed in either cohort. CONCLUSIONS: Our results suggest that according to a mean follow-up of 4 years, the use of thin liners in THA is promising. Longer follow-up is required to assess whether these outcomes are observed later. PMID- 26130286 TI - Microsurgical anatomy of the extra-articular segment of middle genicular artery. AB - PURPOSE: Knowledge of the incompletely studied microsurgical anatomy of the extracapsular part of the middle genicular artery (MGA) could imply an educational value and clinical significance because of the possible risk of injury during knee surgery. METHODS: Thirty formol-fixed cadaveric lower limbs in full extension were dissected and used for the measurements of MGA parameters. A second group of measurements was performed on distal ends of 30 adult femurs. Two fresh injected cadaveric lower limbs were explored by means of multidetector computed tomographic angiography (MDCTA). RESULTS: The MGA originated from the popliteal artery (PA), facing the lateral half of the intercondylar fossa in 16 (53.4 %) specimens, together with the superior lateral genicular artery (SLGA) in ten (33.3 %) cases, or from the same point of origin with SLGA and superior medial genicular artery (SMGA) in 4 (13.3 %) cases. The MGA averaged 15.6 mm in length and 1.8 mm in the outer diameter. After its curved direction the MGA entered the posterior capsule. The average distances of the point of MGA entrance into the joint capsule were as follows: to the lateral femoral epicondyle it was 34.88 mm, to the medial femoral epicondyle 46.38 mm, 5.74 mm lateral to the posterior midline, with an average vertical distance to the femoral subcondylar plane of 28.73 mm. CONCLUSION: This detailed anatomical examination with measurements of the extracapsular part of a MGA could be of clinical importance and useful in knee surgery for the prevention of vascular injury of MGA and PA, as well as in radiological examination of the knee region. PMID- 26130287 TI - The sagittal stem alignment and the stem version clearly influence the impingement-free range of motion in total hip arthroplasty: a computer model based analysis. AB - PURPOSE: The component alignment in total hip arthroplasty influences the impingement-free range of motion (ROM). While substantiated data is available for the cup positioning, little is known about the stem alignment. Especially stem rotation and the sagittal alignment influence the position of the cone in relation to the edge of the socket and thus the impingement-free functioning. Hence, the question arises as to what influence do these parameters have on the impingement-free ROM? METHODS: With the help of a computer model the influence of the sagittal stem alignment and rotation on the impingement-free ROM were investigated. The computer model was based on the CT dataset of a patient with a non-cemented THA. In the model the stem version was set at 10 degrees /0 degrees /-10 degrees and the sagittal alignment at 5 degrees /0 degrees /-5 degrees , which resulted in nine alternative stem positions. For each position, the maximum impingement-free ROM was investigated. RESULTS: Both stem version and sagittal stem alignment have a relevant influence on the impingement-free ROM. In particular, flexion and extension as well as internal and external rotation capability present evident differences. In the position intervals of 10 degrees sagittal stem alignment and 20 degrees stem version a difference was found of about 80 degrees in the flexion and 50 degrees in the extension capability. Likewise, differences were evidenced of up to 72 degrees in the internal and up to 36 degrees in the external rotation. CONCLUSIONS: The sagittal stem alignment and the stem torsion have a relevant influence on the impingement-free ROM. To clarify the causes of an impingement or accompanying problems, both parameters should be examined and, if possible, a combined assessment of these factors should be made. PMID- 26130289 TI - Re: Ling Y-H, Li T, Yuan Z, Haigentz M, Jr., Weber TK, and Perez-Soler R (2007) Erlotinib, an Effective Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Induces p27KIP1 Up-Regulation and Nuclear Translocation in Association with Cell Growth Inhibition and G1/S Phase Arrest in Human Non-Small-Cell Lung Cancer Cell Lines. Mol Pharmacol 72:248-258; doi:10.1124/mol.107.034827. PMID- 26130288 TI - Similar outcomes between two-stage revisions for infection and aseptic hip revisions. AB - PURPOSE: Two-stage revision hip arthroplasty using an antibiotic-loaded spacer is the most widely performed procedure for infected hip arthroplasties. The clinical outcome of this type of surgery compared with aseptic joint revision with exchange of femoral and acetabular components is still controversial due to the relative lack of medium- to long-term follow-up. Therefore, we analysed clinical and radiological outcomes of septic two-stage revisions compared with aseptic hip revision surgeries. METHODS: In this retrospective study we assessed 82 consecutive patients who underwent two-stage revision for septic total hip (45 patients) or one-stage aseptic revision arthroplasty (37 patients). The average follow-up was 53 months for the aseptic group and 55 months for the septic group. For clinical evaluation, we used the Harris Hip Score (HHS) and the Merle d'Aubigne and Postel score. The postoperative pain level was determined with the visual analogue pain scale. RESULTS: The surgeries were performed 124 months (aseptic group) and 119 months (septic group) after primary total hip arthroplasty on average. The main indications for aseptic revision surgeries were aseptic loosening (96%), dislocation (2.2%), and periprosthetic fracture (2.2%). In the clinical outcome patients achieved 75.5 points in the aseptic group and 73.4 points in the septic group in the Harris Hip Score. The Merle d'Aubigne and Postel Score revealed 12.5 points for the aseptic group and 13.1 points for the septic group. Mean level of persisting pain was 0.8 (aseptic group) and 0.4 (septic group) on the visual analogue scale (VAS). Overall survival in the aseptic group was 85.6% at 9.8 years 82.7% at 10.1 years for the septic group, with a repeat revision rate of 8.1% and 6.7%, respectively. CONCLUSIONS: Performing aseptic acetabular and femoral revision hip arthroplasty showed equal clinical outcomes in relation to septic two-stage revision hip surgeries. Our results showed a tendency for better outcome in comparison with the information given in the literature for septic and nonseptic exchange arthroplasties, including a lower rate of re-revisions. PMID- 26130290 TI - Re: Ling Y-H, Lin R, and Perez-Soler R (2008) Erlotinib Induces Mitochondrial Mediated Apoptosis in Human H3255 Non-Small-Cell Lung Cancer Cells with Epidermal Growth Factor ReceptorL858R Mutation through Mitochondrial Oxidative Phosphorylation-Dependent Activation of BAX and BAK Mol Pharmacol 74:793-806; doi:10.1124/mol.107.044396. PMID- 26130291 TI - Liquid crystal polaroid glass electrode from e-waste for synchronized removal/recovery of Cr(+6) from wastewater by microbial fuel cell. AB - This study demonstrates the use of Liquid Crystal coated Polaroid Glass Electrode (LCPGE) material collected from disposed liquid-crystal display (LCD) computer monitor as electrodes in microbial fuel cell (MFC) for the simultaneous reduction/recovery of Cr(+6) from chromium wastewater. Fourier transform infrared spectrum (FT-IR) confirms the presence of NH2, CN, CO and OC and/or COC functional groups in LCPGE. An excellent electrochemical performance with distinct redox peaks were observed in cyclic voltammetry test (100 mV/s). The maximum current density of 110 mA/m(2) (10 mW/m(2)) was achieved by operating MFC in batch mode. At the cathode LCPGE (10.5 cm(2)) interface, toxic Cr(+6) ions readily accepted electrons and formed nontoxic Cr2O3 as confirmed by FT-IR and X ray photoelectron spectroscopy analysis. Moreover, electrochemical impedance analysis shows that bacteria were readily attached to the surface of LCPGE (10.5 cm(2)) within 24 h in a Bioelectrochemical System (BES). PMID- 26130293 TI - Erratum to: Sick leave and disability pension in Hodgkin lymphoma survivors by stage, treatment, and follow-up time-a population-based comparative study. PMID- 26130292 TI - A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy. AB - PURPOSE: Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. METHODS: Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. RESULTS: Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. CONCLUSION: Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. IMPLICATIONS FOR CANCER SURVIVORS: Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results. PMID- 26130294 TI - Mixing of immiscible polymers using nanoporous coordination templates. AB - The establishment of methodologies for the mixing of immiscible substances is highly desirable to facilitate the development of fundamental science and materials technology. Herein we describe a new protocol for the compatibilization of immiscible polymers at the molecular level using porous coordination polymers (PCPs) as removable templates. In this process, the typical immiscible polymer pair of polystyrene (PSt) and poly(methyl methacrylate) (PMMA) was prepared via the successive homopolymerizations of their monomers in a PCP to distribute the polymers inside the PCP particles. Subsequent dissolution of the PCP frameworks in a chelator solution affords a PSt/PMMA blend that is homogeneous in the range of several nanometers. Due to the unusual compatibilization, the thermal properties of the polymer blend are remarkably improved compared with the conventional solvent-cast blend. This method is also applicable to the compatibilization of PSt and polyacrylonitrile, which have very different solubility parameters. PMID- 26130295 TI - Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration. AB - When dengue virus (DENV)-infected mosquitoes use their proboscis to probe into human skin during blood feeding, both saliva and virus are released. During this process, cells from the epidermis and dermis layers of the skin, along with small blood vessels, may get exposed to or infected with DENV. In these microenvironments of the skin, the presence of DENV initiates a complex interplay among the DENV-infected and non-infected neighboring cells at the initial bite site. Previous studies suggested that DENV-infected human dermal fibroblasts (HDFs) participate in the immune response against DENV by secreting soluble mediators of innate immunity. In the present study, we investigated whether DENV infected HDFs activate human dermal microvascular endothelial cells (HDMECs) in co-cultures. Our results suggest that co-cultures of DENV-infected HDFs and HDMECs elicit soluble mediators that are sufficient to reduce viral replication, activate HDMECs, and induce leukocyte migration through HDMEC monolayers. These effects were partly dependent on HDF donor and DENV serotype, which may provide novel insights into the natural variation in host susceptibility to DENV disease. PMID- 26130296 TI - The double burden of under- and overnutrition and nutrient adequacy among Chinese preschool and school-aged children in 2009-2011. AB - BACKGROUND/OBJECTIVES: Coincident with economic development, China has experienced a marked transition from undernutrition to overweight/obesity over the last few decades. We aimed to explore the burden of under- and overnutrition and nutrient adequacy among 2-12-year-old Chinese children. SUBJECTS/METHODS: We included anthropometry, dietary intake and biomarkers from 2-12-year-olds who participated in the 2009-2011 China Health and Nutrition Survey (n=1191 in 2009; n=1648 in 2011). Dietary intakes were compared with the 2013 Chinese Dietary Recommended Intakes. RESULTS: In 2011, ~19% of 2-6-year-old children were underweight, 4% were stunted, 10% were overweight and 12% were obese. Among 7-12 year-old children, stunting was almost 0%, whereas ~21% were underweight, 13% were overweight and 6% were obese in 2011. Overweight and obesity were more prevalent among children from urban areas and higher income households. In particular, 2-6-year-old children from urban areas and higher income households experienced the highest increase in obesity from 2009 to 2011 (P<0.05). Children from urban areas and higher income households had overall higher intakes of total daily energy and most macro- and micronutrients (P<0.05). However, a significant proportion of children did not meet the recommendations for important micronutrients. CONCLUSIONS: Underweight and stunting currently coexist with overweight and obesity among Chinese children <12-year-old. We found critical disparities in the prevalence of under- and overweight/obesity, as well as in nutrient intakes and dietary adequacies between children from different incomes, revealing that the burden of childhood under- and overnutrition may constitute a public health concern in modern China. PMID- 26130297 TI - Consumption of soft drinks and health-related quality of life in the adult population. AB - BACKGROUND/OBJECTIVES: Despite the accumulated evidence on the health risks associated with sugar-sweetened beverages (SSB), the industry has funded mass communication strategies promoting the idea that soft drinks, including SSB, may represent a source of well-being. This study assessed the association between consumption of soft drinks and health-related quality of life (HRQL), as a proxy of well-being, in the adult population of Spain. SUBJECTS/METHODS: The cohort was established in 2008-2010 with 8417 individuals representative of the Spanish population aged 18-60 years. Habitual soft drink consumption was assessed with a validated diet history at baseline. HRQL was measured using the SF-12 questionnaire at baseline and in a subsample of 2132 study participants in 2012. The analyses were performed using linear regression and adjusted for the main confounders. RESULTS: In cross-sectional analyses at baseline, those who drank ?1 serving/day of SSB had a lower (worse) score on the physical composite summary (PCS) of the SF-12 (adjusted linear regression coefficient: -1.08; 95% confidence interval (CI): -1.60 to -0.54) than those who drank <1 serving/week. Results were similar among individuals younger than 35 years (-1.06; 95% CI: -1.79 to -0.32), those who were not dieting (-1.21; 95% CI: -1.80 to -0.62), those who did not lose >5 kg in the previous 4 years (-0.79; 95% CI: -1.87 to 0.29), and in those without morbidity (-1.18; 95% CI: -1.91 to -0.46). Neither SSBs nor artificially sweetened beverages (ASBs) showed an association with the mental composite summary (MCS) of the SF-12. In the prospective analyses, no association was observed between baseline consumption of SSBs or ASBs and the changes in the PCS and MCS score from 2008/2010 to 2012. CONCLUSIONS: No evidence was found that soft drink consumption has a beneficial effect on either the physical or mental dimensions of HRQL. PMID- 26130298 TI - Apparent consumption of refined sugar in Australia (1938-2011). AB - BACKGROUND/OBJECTIVES: In Australia, the Australian Bureau of Statistics discontinued collection of apparent consumption data for refined sugars in 1998/1999. The objectives of this study were to update this data series to determine whether it is a reliable data series that reflects consumption of refined sugars, defined as sucrose in the forms of refined or raw sugar or liquified sugars manufactured for human consumption. SUBJECTS/METHODS: The study used the same methodology as that used by the Australian Bureau of Statistics to derive a refined sugars consumption estimate each year until the collection was discontinued. Sales by Australian refiners, refined sugars imports and the net balance of refined sugars contained in foods imported into, and exported from, Australia were used to calculate total refined sugars use for each year up to 2011. Per capita consumption figures were then derived. RESULTS: During the period 1938-2011, apparent consumption of refined sugars in Australia fell 13.1% from 48.3 to 42.0 kg per head (R(2)=0.74). Between the 1950s and the 1970s, apparent consumption was relatively stable at about 50 kg per person. In the shorter period 1970-2011, refined sugars consumption fell 16.5% from 50.3 to 42.0 kg per head, though greater variability was evident (R(2)=0.53). An alternative data set showed greater volatility with no trend up or down. CONCLUSIONS: The limited variability of the extended apparent consumption series and its consistency with recent national dietary survey data and sugar-sweetened beverage sales data indicate that it is a reliable data set that reflects declining intake of refined sugars in Australia. PMID- 26130299 TI - Perceived energy compensation following various sports: an age and sex comparison. Preliminary observations. AB - Following periods of physical activity, it is not uncommon for exercisers to increase their energy intake as a reward deemed 'earned'. Consumers' awareness of the energy within food and expended from exercise has previously been found to be limited. Therefore, the aim was to investigate whether habitual exercisers (50 adults and 49 children from 5 sports clubs) were able to conceptualise the energy expenditure (EE), following 1 h of their regular sports training, into a quantifiable amount of perceived energy compensation (PEC) in the form of food (chocolate) or drink (sports drink). Mean percentage accuracy for the PEC against EE matched <30% (+/- 29%), a significant underestimation irrespective of sex or sport. Percentage accuracy failed to significantly correlate to age. These findings indicate a necessity to improve nutrition education surrounding the energy costs of exercise relative to the energy contained within foods/drinks for both adults and children. PMID- 26130301 TI - Fast-food and full-service restaurant consumption and daily energy and nutrient intakes in US adults. AB - BACKGROUND/OBJECTIVES: Calorie intake and diet quality are influenced by the source of food and the place of consumption. This study examines the impacts of fast-food and full-service restaurant consumption on daily energy and nutrient intakes in US adults. SUBJECTS/METHODS: Nationally representative data of 18,098 adults 18 years of age and above from the National Health and Nutrition Examination Survey 2003-2010 waves were analyzed. Outcomes included daily intake of total calories and 24 nutrients of public health concern. The key predictors were any food/beverage consumption in a day from fast-food or full-service restaurant, differentiated by consumption at home versus away from home. First difference estimator addressed confounding bias from time-invariant unobservables such as personal food/beverage preferences by using within-individual variations in diet and restaurant consumption status between two nonconsecutive 24-h dietary recalls. RESULTS: Fast-food and full-service restaurant consumption, respectively, were associated with a net increase in daily total energy intake of 190.29 and 186.74 kcal, total fat of 10.61 and 9.58 g, saturated fat of 3.49 and 2.46 g, cholesterol of 10.34 and 57.90 mg, and sodium of 297.47 and 411.92 mg. The impact of fast-food and full-service restaurant consumption on energy and nutrient intakes differed by sex, race/ethnicity, education, income and weight status. Increased total energy, total fat, saturated fat, cholesterol and sodium intake were substantially larger when full-service restaurant food was consumed away from home than at home. CONCLUSIONS: A holistic policy intervention is warranted to target the American's overall dining-out behavior rather than fast food consumption alone. PMID- 26130300 TI - The evaluation of inflammatory and oxidative stress biomarkers on coffee-diabetes association: results from the 10-year follow-up of the ATTICA Study (2002-2012). AB - BACKGROUND/OBJECTIVES: The purpose of this work was to investigate the association between coffee drinking and diabetes development and potential mediation by oxidative stress and inflammatory biomarkers. SUBJECTS/METHODS: In 2001-2002, a random sample of 1514 men (18-87 years old) and 1528 women (18-89 years old) were selected to participate in the ATTICA study (Athens metropolitan area, Greece). A validated food-frequency questionnaire was used to assess coffee drinking (abstention, casual, habitual) and other lifestyle and dietary factors. Evaluation of oxidative stress and inflammatory markers was also performed. During 2011-2012, the 10-year follow-up of the ATTICA study was carried out. The outcome of interest in this work was incidence of type 2 diabetes, defined according to American Diabetes Association criteria. RESULTS: During follow-up, 191 incident cases of diabetes were documented (incidence 13.4% in men and 12.4% in women). After various adjustments, individuals who consumed ?250 ml of coffee (~1.5cup) had 54% lower odds of developing diabetes (95% confidence interval: 0.24, 0.90), as compared with abstainers. A dose-response linear trend between coffee drinking and diabetes incidence was also observed (P for trend=0.017). When controlling for several oxidative stress and inflammatory biomarkers, the inverse association between habitual coffee drinking and diabetes was found to be mediated by serum amyloid-A levels. CONCLUSIONS: This work highlights the significance of long-term habitual coffee drinking against diabetes onset. The anti-inflammatory effect of several coffee components may be responsible for this protection. PMID- 26130303 TI - The electronic structure of quasi-free-standing germanene on monolayer MX (M = Ga, In; X = S, Se, Te). AB - For the first time by using the ab initio density functional theory, the stability and electronic structures of germanene on monolayer GaS, GaSe, GaTe and InSe have been investigated. Germanene preserves its buckled-honeycomb structure on all the studied substrates similar to the free-standing case. Moreover, germanene stays neutral and preserves its Dirac-cone-like band structure on monolayer GaTe and InSe. In these two cases, a bandgap of 0.14-0.16 eV opens at the Dirac point of germanene, while the effective masses remain as small as 0.05 0.06 times the free-electron mass. The estimated carrier mobility is up to 2.2 * 10(5) cm(2) V(-1) s(-1). These features show that monolayer GaTe and InSe are promising as substrates for germanene devices. PMID- 26130302 TI - No evidence of enhanced satiety following whey protein- or sucrose-enriched water beverages: a dose response trial in overweight women. AB - BACKGROUND/OBJECTIVES: To compare the effect of low-dose whey protein-enriched and sucrose-enriched water beverages on postprandial satiety and energy intake. SUBJECTS/METHODS: Sixty overweight and obese women were given water-based protein and carbohydrate (CHO) beverages or placebo on six different occasions in a double-blind, randomised cross-over study. The beverages were 2 (178 kJ) and 4% (348 kJ) protein-enriched water (Clear Protein8855), 2 (157 kJ), 4 (314 kJ) and 10% (785 kJ) sucrose-enriched water, and a sweetened water control. Beverages were matched for volume, colour, flavour and sweetness. A standardised evening meal was provided before each study day and a standardised breakfast upon arrival at the clinic at 0900 hours. The beverage preload was given midmorning at 1100 hours, and an ad libitum outcome lunch meal at 1300 hours. Subjective appetitive responses were recorded through the day until 1500 hours using visual analogue scales. RESULTS: Fifty-five participants completed all six beverage conditions. Neither protein nor sucrose preloads decreased any of hunger, fullness, thoughts of food or satisfaction when compared with the sweetened water control beverage (all, P>0.05). There was also no significant effect on ad libitum energy or macronutrient intake at the outcome meal (P>0.05), with no compensation for the energy consumed within the preload beverages. CONCLUSIONS: There was no evidence of increased postprandial satiety or compensation for energy content at an outcome lunch meal when a water beverage was supplemented with up to 4% (w/w) whey protein or 10% (w/w) sucrose, in a group of overweight but unrestrained young and middle-aged women. PMID- 26130304 TI - Biomechanics Associated with Patellofemoral Pain and ACL Injuries in Sports. AB - BACKGROUND: Knee injuries are prevalent among a variety of competitive sports and can impact an athlete's ability to continue to participate in their sport or, in the worst case, end an athlete's career. OBJECTIVE: The aim was to evaluate biomechanics associated with both patellofemoral pain syndrome (PFPS) and anterior cruciate ligament (ACL) injuries (in sports involving landing, change in direction, or rapid deceleration) across the three time points frequently reported in the literature: pre-injury, at the time of injury, and following injury. METHODS: A search of the literature was conducted for research evaluating biomechanics associated with ACL injury and PFPS. The Web of Science, SPORTDiscus, EBSCO, PubMed, and CINAHL databases, to March 2015, were searched, and journal articles focused on ACL injuries and PFPS in sports that met the inclusion criteria were reviewed. The search methodology was created with the intent of extracting case-control, case, and cohort studies of knee injury in athletic populations. The search strategy was restricted to only full-text articles published in English. These articles were included in the review if they met all of the required selection criteria. The following inclusion criteria were used: (1) The study must report lower extremity biomechanics in one of the following settings: (a) a comparison of currently injured and uninjured participants, (b) a prospective study evaluating risk factors for injury, or (c) a study reporting on the injury event itself. (2) The study must include only currently active participants who were similar at baseline (i.e. healthy, high school level basketball players currently in-season) and include biomechanical analysis of either landing, change in direction, or rapid deceleration. (3) The study must include currently injured participants. The studies were graded on the basis of quality, which served as an indication of risk of bias. An adapted version of the 'Strengthening the Reporting of Observational Studies in Epidemiology' (STROBE) guidelines was used to rate observational research. RESULTS: Fifteen journal articles focusing on ACL injuries and PFPS in sports met the inclusion criteria. These included three associated with both ACL injuries and PFPS across multiple time points. There was limited evidence for an association between ankle biomechanics and knee injury, with only one ACL injury study identifying decreased plantar flexion in association with injury. LIMITATIONS: Only prospective studies can determine biomechanical risk factors associated with ACL injuries and PFPS. Case studies and case-control studies do not allow for the determination of risk factors associated with both ACL injuries and PFPS as there is no certainty regarding the presence of the observed biomechanics prior to the onset of injury. Further, each study design has its own set of limitations. Lastly, the majority of the studies included in this review had adult female participants. CONCLUSION: By evaluating several different study designs looking at knee injuries during high-risk manoeuvres, we were able to obtain a holistic perspective of biomechanics associated with PFPS and ACL injuries. Looking at different biomechanical research approaches allowed us to assess not only the mechanism of injury, but also to look for commonalities in biomechanics (in particular, altered frontal plane mechanics at the knee and altered sagittal plane mechanics at the knee and hip) between injured and uninjured participants pre-injury, at the time of injury, and following injury, to better understand potential causes of PFPS and ACL injury. Development of injury prevention programmes should focus on correcting these mechanics observed across the three time points during high-risk manoeuvres as this may help decrease the prevalence of ACL injury and PFPS. Programmes focusing not only on neuromuscular training, but also skill-specific training focused on correcting mechanics during these high-risk manoeuvres may be of greatest benefit regarding prevention. Future research should consider the impact of cumulative loading on knee injury risk. Additionally, better techniques for assessing mechanics in-game are needed in order to facilitate injury prevention and screening strategies. PMID- 26130305 TI - Comparative study of IDH1 mutations in gliomas by high resolution melting analysis, immunohistochemistry and direct DNA sequencing. AB - Patients with glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a better prognosis than those with gliomas with wild-type IDH1. IDH1 analysis has become part of the standard diagnostic procedure and a promising tool used for stratification in clinical trials. The present study aimed to compare high resolution melting (HRM) analysis, immunohistochemistry (IHC) and direct DNA sequencing for the detection of IDH mutations in gliomas. Fifty-one formalin-fixed paraffin-embedded tumor samples were selected. For the HRM analysis and direct DNA sequencing, DNA was extracted from the tissues. For IHC, sections were stained with an anti-IDH1-R132H specific antibody. The HRM analysis method identified 33 cases of IDH1 gene mutations, and all mutations occurred at the R132H site. There were 33 cases of IDH1 gene mutations found by IHC, which was consistent with that identified using the HRM analysis method. However, only 30 IDH1 samples were confirmed by sequencing, in which mutations occurred at the IDH1 exon 4 R132H site. No mutation was detected in the other three of these 33 cases (two grade II oligodendroglioma and one grade II diffuse astrocytoma) by sequencing, while IHC was positive for IDH1 R132H. The results showed that the mutation detection rate was not identified to be significantly different (P=0.250) when determined by the HRM analysis method or by direct DNA sequencing, as the concordant rate between the two methods was high (kappa=0.866). The HRM analysis method in glioma IDH1 gene mutation detection has advantages of high sensitivity, good repeatability, simple operation and accurate results. It provides a novel method for detecting mutations of the IDH1 gene in paraffin embedded tissue samples of clinical glioma. Related to a small amount of sample, there was no evidence showing that HRM analysis method is superior to IHC. Direct DNA sequencing, HRM analysis and IHC results were consistent; however, HRM and IHC are more sensitive than direct DNA sequencing in identifying the IDH1-R132H mutation. PMID- 26130306 TI - Potential Health Impact of Environmentally Released Micro- and Nanoplastics in the Human Food Production Chain: Experiences from Nanotoxicology. AB - High concentrations of plastic debris have been observed in the oceans. Much of the recent concern has focused on microplastics in the marine environment. Recent studies of the size distribution of the plastic debris suggested that continued fragmenting of microplastics into nanosized particles may occur. In this review we assess the current literature on the occurrence of environmentally released micro- and nanoplastics in the human food production chain and their potential health impact. The currently used analytical techniques introduce a great bias in the knowledge, since they are only able to detect plastic particles well above the nanorange. We discuss the potential use of the very sensitive analytical techniques that have been developed for the detection and quantification of engineered nanoparticles. We recognize three possible toxic effects of plastic particles: first due to the plastic particles themselves, second to the release of persistent organic pollutant adsorbed to the plastics, and third to the leaching of additives of the plastics. The limited data on microplastics in foods do not predict adverse effect of these pollutants or additives. Potential toxic effects of microplastic particles will be confined to the gut. The potential human toxicity of nanoplastics is poorly studied. Based on our experiences in nanotoxicology we prioritized future research questions. PMID- 26130307 TI - Distinct Metabolomic Profiles of Papillary Thyroid Carcinoma and Benign Thyroid Adenoma. AB - Papillary thyroid carcinoma (PTC) and benign thyroid adenoma (BTA) are the most common head and neck tumors. However, the metabolic differences between PTC and BTA have not been characterized. The aim of this study was to identify the metabolic profiles of these two types of tumors using a metabolomics approach. Tumors and adjacent nontumor specimens collected from 57 patients with PTC and 48 patients with BTA were profiled using gas chromatography-time-of-flight mass spectrometry and ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. A panel of 46 and 44 differentially expressed metabolites were identified in the PTC and BTA specimens, respetively, and compared with nontumor tissues. Common metabolic signatures, as characterized by increased glycolysis, amino acid metabolism, one carbon metabolism and tryptophan metabolism, were found in both types of tumors. Purine and pyrimidine metabolism was significantly elevated in the PTC specimens, and taurine and hypotaurine levels were also higher in the PTC tissues. Increased fatty acid and bile acid levels were found, especially in the BTA tissues. The metabolic profiles of the PTC and BTA tissues include both similar and remarkably different metabolites, suggesting the presence of common and unique mechanistic pathways in these types of tumors during tumorigenesis. PMID- 26130308 TI - Modeling and simulation of fructooligosaccharides synthesis in a batch basket reactor. AB - Fructooligosaccharides (FOS) production was carried out in a batch basket reactor with immobilized fructosyltransferase from Rhodotorula sp. from 500*10(3) g m(-3) of sucrose in 50 mM sodium acetate buffer at pH 6.0, 48 degrees C at 85 rpm and with an activity of 22.44*10(3) U m(-3). The experimental data were well adjusted to the mathematical model for FOS production using SIMULINK((r)) (MATLAB((r))). The highest regression coefficient (R(2)>90%) and the lowest percentual residual standard deviation (%RSD<4.0) and chi-square (chi(2) <1.0) were obtained for sucrose (GF), kestose (GF2) and total FOS. The mass transfer coefficient (kL) was determined as 5.6*10(-5) m h(-1) and the diffusivity (DS) was 2.11*10(-11) m(2) s(-1). The best predicted FOS yield (after 96 h) was 60.62%, with an equivalent productivity of 3.16*10(3) g m(-3) h(-1). These results reaffirm the good potential of this enzyme for industrial application and, in addition, are in conformation to other studies conducted with the same enzyme from the same and different microbial sources. PMID- 26130309 TI - Characteristics of locomotion efficiency of an expanding-extending robotic endoscope in the intestinal environment. AB - Robotic endoscopes with locomotion ability are among the most promising alternatives to traditional endoscopes; the locomotion ability is an important factor when evaluating the performance of the robot. This article describes the research on the characteristics of an expanding-extending robotic endoscope's locomotion efficiency in real intestine and explores an approach to improve the locomotion ability in this environment. In the article, the robot's locomotion efficiency was first calculated according to its gait in the gut, and the reasons for step losses were analyzed. Next, dynamical models of the robot and the intestine were built to calculate the step losses caused by failed anchoring and intestinal compression/extension. Based on the models and the calculation results, methods for reducing step losses were proposed. Finally, a series of ex vivo experiments were carried out, and the actual locomotion efficiency of the robot was analyzed on the basis of the theoretical models. In the experiment, on a level platform, the locomotion efficiency of the robot varied between 34.2% and 63.7%; the speed of the robot varied between 0.62 and 1.29 mm/s. The robot's efficiency when climbing a sloping intestine was also tested and analyzed. The proposed theoretical models and experimental results provide a good reference for improving the design of robotic endoscopy. PMID- 26130310 TI - Supervised segmentation of MRI brain images using combination of multiple classifiers. AB - Segmentation of different tissues is one of the initial and most critical tasks in different aspects of medical image processing. Manual segmentation of brain images resulted from magnetic resonance imaging is time consuming, so automatic image segmentation is widely used in this area. Ensemble based algorithms are very reliable and generalized methods for classification. In this paper, a supervised method named dynamic classifier selection-dynamic local training local tanimoto index, which is a member of combination of multiple classifiers (CMCs) methods is proposed. The proposed method uses dynamic local training sets instead of a full statics one and also it change the classifier rank criterion properly for brain tissue classification. Selection policy for combining the different decisions is implemented here and the K-nearest neighbor algorithm is used to find the best local classifier. Experimental results show that the proposed method can classify the real datasets of the internet brain segmentation repository better than all single classifiers in ensemble and produces significantly improvement on other CMCs methods. PMID- 26130311 TI - Cryptosporidium ubiquitum in Venezuela: First report in a paediatric patient with acute diarrhoea. PMID- 26130312 TI - Emergence of Providencia rettgeri NDM-1 in two departments of Colombia, 2012 2013. AB - INTRODUCTION: In Colombia, between 2012 and 2013, 19 isolates with NDM were identified, of which 14 corresponded to Providencia rettgeri. METHODS: The isolates were identified by Vitek-2, and antimicrobial susceptibility was evaluated by broth microdilution. The carbapenemase phenotypes were determined with Modified Hodge Test and synergy tests with EDTA/SMA and APB, the genotypes by PCR using specific primers for KPC, GES, IMP, VIM, OXA-48 and NDM, and genetic relationships were established with DiversiLab. RESULTS: The isolates were resistant to carbapenems, third-generation cephalosporins, piperacillin tazobactam, amikacin, gentamicin and tigecycline, except aztreonam. All isolates were positive for EDTA/SMA and NDM-1, and negative for APB and other carbapenemases. Two genetic groups, group 1 (n=9 isolates), group 2 (n=4 isolates) and an isolate defined as not genetically related. CONCLUSION: This work describes the circulating of NDM-1-producing P. rettgeri in Colombia. PMID- 26130313 TI - A phthalazine-based two-in-one chromogenic receptor for detecting Co(2+) and Cu(2+) in an aqueous environment. AB - A new multifunctional and highly selective chemosensor for Co(2+) and Cu(2+) was designed and synthesized. could simultaneously detect both Co(2+) and Cu(2+) by changing its color from pale yellow to pink and to orange in a near-perfect aqueous solution. The binding modes of to Co(2+) and Cu(2+) were determined to be a 2 : 1 complexation stoichiometry through Job's plot, ESI-mass spectrometry analysis and (1)H NMR titration. The detection limits (1.5 and 2.1 MUM) of for Co(2+) and Cu(2+) were lower than the DEP guidelines (1.7 MUM for Co(2+)) and the WHO guidelines (31.5 MUM for Cu(2+)) for drinking water. The chemosensor could be used to quantify Co(2+) and Cu(2+) in water samples. Moreover, could be used as a practical, visible colorimetric test kit for both Co(2+) and Cu(2+). The sensing mechanisms of Co(2+) and Cu(2+) by were supported by theoretical calculations. PMID- 26130314 TI - Platelet-Rich Plasma: A Study of the Variables that May Influence Its Effect on Bone Regeneration. AB - BACKGROUND: Currently, the use of platelet-rich plasma in bone regeneration is a real option, although more than one opinion has alerted us to the absence of clinical benefits. PURPOSE: Analysis of the factors able to modify the characteristics of the platelet preparation obtained by Curasan, Plasma Rich in Growth Factors (PRGF), Platelet Concentrate Collection System (PCCS) and SmartPrep systems, relating them to the type of clinical application and the final bone regeneration achieved. MATERIALS AND METHODS: A search was conducted in PubMed using the keywords "platelet-rich plasma," "PRP," "platelet rich growth factors," and "oral bone regeneration." Four widely accepted protocols for the obtention of PRP (above) were analyzed. Any clinical studies with controls, using the four preparation protocols and with a 4 to 6 weeks follow-up period were compared. The protocols were also grouped according to the type of PRP application: PRP-alone, with bone, or with bone substitutes. RESULTS: Bone regeneration was not achieved in any of the cases using PRP obtained by Curasan and PCCS systems, whereas PRP obtained by SmartPrep achieved it only in one in three published cases and PRGF in one in six. CONCLUSION: Based on the poor results observed in current literature, the use of PRP in oral surgery cannot be recommended. PMID- 26130315 TI - EFFICACY OF ESTRADIOL IN PERIMENOPAUSAL DEPRESSION: SO MUCH PROMISE AND SO FEW ANSWERS. AB - BACKGROUND: Controversy regarding the antidepressant efficacy of hormone replacement therapy (HRT) stems almost from its inception and reflects the same methodological inconsistencies that have compromised efforts to determine whether the perimenopause is accompanied by an increase in mood symptoms or depression. Methodologic differences of note (other than study design) include menopausal state (perimenopause vs. postmenopause), determination of state (earlier studies used age as a proxy measure), baseline symptomatology (asymptomatic vs. depressive symptoms vs. syndromic depression), route of hormone administration (transdermal vs. oral), and symptom or syndrome measure. Zweifel and O'Brien's 1997 meta-analysis included 26 studies of the effects of menopausal HRT on depressed mood and revealed an overall effect size of 0.68. This moderate to large effect size, showing lower ratings of depressed mood in treated patients compared with controls, implicated HRT as a potential treatment of or prophylactic for depression in menopausal women. Since this publication, multiple studies have aimed to discern the relationship between HRT and menopausal mood. METHODS: The purpose of this systematic review is to examine the findings and quality of the evidence amassed since Zweifel and O'Brien's meta-analysis. RESULTS: Of the 24 studies meeting criteria for review, only five RCTs examined depressed subjects, and only two of the study samples were solely perimenopausal. CONCLUSIONS: One can generalize from the studies reviewed here only with great caution, but there is little evidence to support the use of estradiol to improve mood in nondepressed patients (not surprisingly) and some evidence to support the antidepressant efficacy of estradiol in perimenopausal but not postmenopausal women. PMID- 26130316 TI - Narrowband ultraviolet B phototherapy in psoriasis reduces proinflammatory cytokine levels and improves vitiligo and neutrophilic asthma. PMID- 26130317 TI - Intravoxel incoherent motion diffusion-weighted MRI for characterizing regional variability and monitoring serial changes of parameters in rabbit VX2 liver tumors. AB - PURPOSE: To characterize intravoxel incoherent motion (IVIM) parameters in different regions of interest (ROIs) of rabbit VX2 liver tumors during a follow up of 4 weeks. MATERIALS AND METHODS: This study was approved by the Institutional Animal Care and Use Committee. In 18 VX2 liver tumor-bearing rabbits, IVIM DW imaging was serially performed at the 2nd, 3rd, and 4th week separately after tumor implantation at 1.5T by using 12 b values. Three ROIs were drawn on the apparent diffusion coefficient (ADC) maps, including the whole lesion, the visibly most restricted diffusion area (MRDA), and peripheral area of tumor. For each ROI of tumors, serial changes in ADC and D, D*, and f at three timepoints were calculated. The differences of IVIM parameters in different ROIs of tumors at each timepoint were compared. RESULTS: Serial measurements of f in all three ROIs (P = 0.000, P = 0.002, and P = 0.000), ADC for the whole lesion, MRDA (P = 0.000 and P = 0.024), and D for MRDA (P = 0.001) from the 2nd to 4th week illustrated a statistical difference. The overall comparison of ADC (P = 0.000, P = 0.014, and P = 0.000), D (P = 0.000, P = 0.001, and P = 0.000), and f (P = 0.001, P = 0.001, and P = 0.000) for three tumor regions at weeks 2, 3, and 4 showed significant differences. D* in all three ROIs at each timepoint showed no significant differences (P = 0.612, P = 0.723, and P = 0.699; 95% confidence interval: 0.184-0.950). CONCLUSION: The peripheral area of tumor could be used as an alternative to the whole lesion as ROIs to assess the VX2 liver tumor with IVIM DW imaging, and in the period between weeks 2 and 3. PMID- 26130318 TI - Electron-Poor Thiophene 1,1-Dioxides: Synthesis, Characterization, and Application as Electron Relays in Photocatalytic Hydrogen Generation. AB - The synthesis and characterization of electron-poor thiophene 1,1-dioxides bearing cyanated phenyl groups are reported. The electron-accepting nature of these compounds was evaluated by cyclic voltammetry, and highly reversible and facile reductions were observed for several derivatives. Moreover, some of the reduced thiophene dioxides form colorful anions, which were investigated spectroelectrochemically. Photoluminescence spectra of the electron-deficient sulfones were measured in CH2 Cl2, and they emit in the blue-green region with significant variation in the quantum yield depending on the aryl substituents. By expanding the degree of substitution on the phenyl rings, quantum yields up to 34 % were obtained. X-ray diffraction data are reported for two of the thiophene 1,1 dioxides, and the electronic structure was probed for all synthesized derivatives through DFT calculations. The dioxides were also examined as electron relays in a photocatalytic water reduction reaction, and they showed potential to boost the efficiency. PMID- 26130319 TI - Variation in the Diagnosis and Management of Appendicitis at Canadian Pediatric Hospitals. AB - OBJECTIVES: The objective was to characterize the variations in practice in the diagnosis and management of children admitted to hospitals from Canadian pediatric emergency departments (EDs) with suspected appendicitis, specifically the timing of surgical intervention, ED investigations, and management strategies. METHODS: Twelve sites participated in this retrospective health record review. Children aged 3 to 17 years admitted to the hospital with suspected appendicitis were eligible. Site-specific demographics, investigations, and interventions performed were recorded and compared. Factors associated with after-hours surgery were determined using generalized estimating equations logistic regression. RESULTS: Of the 619 children meeting eligibility criteria, surgical intervention was performed in 547 (88%). After-hours surgery occurred in 76 of the 547 children, with significant variation across sites (13.9%, 95% confidence interval = 7.1% to 21.6%, p < 0.001). The overall perforation rate was 17.4% (95 of 547), and the negative appendectomy rate was 6.8% (37 of 547), varying across sites (p = 0.004 and p = 0.036, respectively). Use of inflammatory markers (p < 0.001), blood cultures (p < 0.001), ultrasound (p = 0.001), and computed tomography (p = 0.001) also varied by site. ED administration of narcotic analgesia and antibiotics varied across sites (p < 0.001 and p = 0.001, respectively), as did the type of surgical approach (p < 0.001). After-hours triage had a significant inverse association with after-hours surgery (p = 0.014). CONCLUSIONS: Across Canadian pediatric EDs, there exists significant variation in the diagnosis and management of children with suspected appendicitis. These results indicate that the best diagnostic and management strategies remain unclear and support the need for future prospective, multicenter studies to identify strategies associated with optimal patient outcomes. PMID- 26130320 TI - Melatonin controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance. AB - Experimental autoimmune encephalomyelitis (EAE), the experimental model for multiple sclerosis (MS), is triggered by myelin-specific Th1 and Th17 cells. The immunomodulatory activities of melatonin have been shown to be beneficial under several conditions in which the immune system is exacerbated. Here, we sought to elucidate the basis of the melatonin protective effect on EAE by characterizing the T effector/regulatory responses, particularly those of the memory cell subsets. Melatonin was tested for its effect on Th1, Th17 and T regulatory (Treg) cells in the lymph nodes and CNS of immunodominant peptide of myelin oligodendrocyte glycoprotein (pMOG)-immunized and EAE mice, respectively. The capacity of melatonin to ameliorate EAE as well as modifying both T cell response and effector/regulatory balance was surveyed. T cell memory subsets and CD44, a key activation marker involved in the EAE pathogenesis, were also examined. Melatonin protected from EAE by decreasing peripheral and central Th1/Th17 responses and enhancing both the Treg frequency and IL-10 synthesis in the CNS. Melatonin reduced the T effector memory population and its pro-inflammatory response and regulated CD44 expression, which was decreased in T effector cells and increased in Tregs. The alterations in the T cell subpopulations were associated with a reduced mononuclear infiltration (CD4 and CD11b cells) of the melatonin-treated mice CNS. For the first time, we report that melatonin protects against EAE by controlling peripheral and central T effector/regulatory responses, effects that might be partially mediated by CD44. This immunomodulatory effect on EAE suggests that melatonin may represent an effective treatment option for MS. PMID- 26130321 TI - New diagnostic approach to diagnosis of achalasia after recent Chicago classification. PMID- 26130322 TI - The ten "diseases" that are not true diseases. PMID- 26130323 TI - Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract. AB - PURPOSE: Vitamin D is well known for its effects on bone mineralisation but has also been attributed immunomodulatory properties. It positively influences human health, but in vivo data describing vitamin D effects on the human gut microbiome are missing. We aimed to investigate the effects of oral vitamin D3 supplementation on the human mucosa-associated and stool microbiome as well as CD8(+) T cells in healthy volunteers. METHODS: This was an interventional, open label, pilot study. Sixteen healthy volunteers (7 females, 9 males) were endoscopically examined to access a total of 7 sites. We sampled stomach, small bowel, colon, and stools before and after 8 weeks of vitamin D3 supplementation. Bacterial composition was assessed by pyrosequencing the 16S rRNA gene (V1-2), and CD8(+) T cell counts were determined by flow cytometry. RESULTS: Vitamin D3 supplementation changed the gut microbiome in the upper GI tract (gastric corpus, antrum, and duodenum). We found a decreased relative abundance of Gammaproteobacteria including Pseudomonas spp. and Escherichia/Shigella spp. and increased bacterial richness. No major changes occurred in the terminal ileum, appendiceal orifice, ascending colon, and sigmoid colon or in stools, but the CD8(+) T cell fraction was significantly increased in the terminal ileum. CONCLUSION: Vitamin D3 modulates the gut microbiome of the upper GI tract which might explain its positive influence on gastrointestinal diseases, such as inflammatory bowel disease or bacterial infections. The local effects of vitamin D demonstrate pronounced regional differences in the response of the GI microbiome to external factors, which should be considered in future studies investigating the human microbiome. PMID- 26130324 TI - Association between inflammatory potential of diet and mortality in the Iowa Women's Health study. AB - PURPOSE: Chronic diseases such as cancer and cardiovascular disease (CVD) are well-established causes of disability and premature deaths. Dietary components that are known to affect chronic inflammation have been implicated in the etiology and prognosis of these chronic diseases. We examined the ability of the dietary inflammatory index (DII) to predict overall, cancer and CVD mortality in the Iowa Women's Health study. METHODS: The DII was computed from baseline dietary intake assessed in this cohort of 37,525 women, who were aged 55-69 years when enrolled starting in 1986. During the follow-up period, through December 31, 2010, in a total of 17,793 deaths, 5044 cancer- and 6528 CVD-related deaths were identified through mortality record linkage. Cox proportional hazards regression was used to estimate hazard ratios (HR) with DII expressed both as a continuous variable and as quartiles. RESULTS: Comparing subjects in DII Quartile 4 versus Quartile 1, modest positive associations were noted for all-cause mortality (HRQ4vsQ1 1.07; 95 % CI 1.01-1.13; p-trend = 0.006), digestive cancer mortality (HRQ4vsQ1 1.19; 95 % CI 1.00-1.43; p-trend = 0.05), CVD mortality (HRQ4vsQ1 1.09; 95 % CI 1.01-1.18; p-trend = 0.08), non-cancer/non-CVD/non-acute mortality (HRQ4vsQ1 1.09; 95 % CI 1.00-1.19; p-trend = 0.19), coronary heart disease (CHD) mortality (HRQ4vsQ1 1.17; 95 % CI 1.05-1.30; p-trend = 0.001) and chronic obstructive pulmonary disease (COPD) mortality (HRQ4vsQ1 1.43; 95 % CI 1.18-1.75; p-trend = 0.0006). No substantial associations were observed for mortality from stroke, Alzheimer's disease or unspecified dementia. CONCLUSION: These results indicate that a pro-inflammatory diet, as evidenced by higher DII scores, may be associated with total mortality as well as mortality from digestive cancer, CVD, CHD and COPD. PMID- 26130325 TI - Serum 25-hydroxyvitamin D is associated with reduced verbal episodic memory in healthy, middle-aged and older adults. AB - BACKGROUND: There is increasing evidence supporting an association of higher serum vitamin D concentration with better cognitive performance in older individuals. However, to date, consideration of the putative association between vitamin D and cognition has been based principally on studies investigating clinical participant samples manifesting vitamin D deficiency, particularly in older people. Moreover, relationships between vitamin D and cognition are typically not considered in the context of counter-regulatory calcium-modulating hormones or calcium homeostasis. OBJECTIVE: Serum vitamin D/bioactive (ionised) calcium/parathyroid hormone homeostasis was considered in the context of cognitive performance in healthy, middle-aged and older individuals. DESIGN: A cross-sectional sample of 179 participants between the ages of 47-84 years was recruited for this study (114 females, 65 males). Participants provided fasting blood samples for analysis of serum 25-hydroxyvitamin D levels, ionised calcium (iCa) and parathyroid hormone (PTH) and completed cognitive measures of verbal episodic learning and memory. RESULTS: Serum 25-hydroxyvitamin D concentrations were negatively associated (with and without covariates of age, gender, depression and NART scores, iCa, and PTH) with measures of verbal episodic learning and memory, in particular with trial 5 of the Rey Auditory Verbal Learning Test (RAVLT) and long-delay free recall on the RAVLT. CONCLUSION: Overall, the findings from this study suggest an association between higher vitamin D status and poorer performance on verbal episodic memory in middle-aged and older individuals with normal vitamin D-calcium-PTH homeostasis. Despite requiring replication in other participant samples, this is a potentially important finding as it indicates that it may not be beneficial from a cognitive perspective to provide vitamin D supplements in individuals with already adequate vitamin D status. PMID- 26130326 TI - MnSOD and CAT polymorphisms modulate the effect of the Mediterranean diet on breast cancer risk among Greek-Cypriot women. AB - PURPOSE: Oxidative stress arises due to a cellular imbalance in oxidants and antioxidants and/or due to an altered activity of antioxidant enzymes, caused by SNPs. Oxidative stress increases susceptibility to breast cancer (BC) risk, and we previously showed that the Mediterranean diet (MD), which is rich in antioxidants, reduces BC risk in Greek-Cypriot women. Here, we investigated the effect of MnSOD (p.Val16Ala, rs4880) and CAT (-262C>T, rs1001179) SNPs on the association between the MD and BC risk in the case-control study of BC MASTOS in Cyprus. METHODS: Dietary intake data were obtained using a 32-item food frequency questionnaire, from which a dietary pattern was previously derived, using principal component analysis. This pattern included high loadings of vegetables, fruit, legumes and fish, a combination that closely resembles the MD and was used as our dietary variable. RESULTS: High vegetable intake lowered BC risk in women with at least one MnSOD Val allele (ORHigh vs. Low for Val/Val = 0.56, 95 % CI 0.35-0.88, for Val/Ala = 0.57, 95 % CI 0.39-0.82), or one CAT -262C allele (ORHigh vs. Low for -262CC = 0.66, 95 % CI 0.47-0.92, for -262CT = 0.53, 95 % CI 0.35-0.81). High fish intake conferred a decreased BC risk of CAT -262CC women (ORQ4 vs. Q1 0.66, 95 % CI 0.47-0.92) compared with the CAT -262TT women and low fish intake (ORQ2 vs. Q1 2.79, 95 % CI 1.08-7.17). Additionally, high fish intake reduced BC risk in MnSOD Val/Val women (ORQ4 vs. Q1 0.63, 95 % CI 0.40-0.98). p interaction values were, however, not statistically significant. CONCLUSION: Our results demonstrate that the antioxidative effects of the MD against BC risk may be enhanced by the wild-type alleles of the MnSOD or CAT SNPs among Greek-Cypriot women. PMID- 26130327 TI - 5-Fluorouracil preferentially sensitizes mutant KRAS non-small cell lung carcinoma cells to TRAIL-induced apoptosis. AB - Mutations in the KRAS gene are very common in non-small cell lung cancer (NSCLC), but effective therapies targeting KRAS have yet to be developed. Interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent inducer of cell death, has increased following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and in xenograft models. However, results from clinical trials of TRAIL based therapy are disappointingly modest at best and many have demonstrated a lack of therapeutic benefit. Current research has focused on selecting a subpopulation of cancer patients who may benefit from TRAIL-based therapy and identifying best drugs to work with TRAIL. In the current study, we found that NSCLC cells with a KRAS mutation were highly sensitive to treatment with TRAIL and 5-fluorouracil (5FU). Compared with other chemotherapeutic agents, 5FU displayed the highest synergy with TRAIL in inducing apoptosis in mutant KRAS NSCLC cells. We also found that, on a mechanistic level, 5FU preferentially repressed survivin expression and induced expression of TRAIL death receptor 5 to sensitize NSCLC cells to TRAIL. The combination of low-dose 5FU and TRAIL strongly inhibited xenograft tumor growth in mice. Our results suggest that the combination of TRAIL and 5FU may be beneficial for patients with mutant KRAS NSCLC. PMID- 26130328 TI - The Significance of the Discordant Occurrence of Lens Tumors in Humans versus Other Species. AB - PURPOSE: The purpose of this study was to determine in which species and under what conditions lens tumors occur. DESIGN: A review of databases of available human and veterinary ocular pathologic material and the previously reported literature. PARTICIPANTS: Approximately 18 000 patients who had ocular surgical specimens submitted and studied at the University of Wisconsin School of Medicine and Public Health between 1920 and 2014 and 45 000 ocular veterinary cases from the Comparative Ocular Pathology Laboratory of Wisconsin between 1983 and 2014. METHODS: Material in 2 major archived collections at the University of Wisconsin medical and veterinary schools were studied for occurrence of lens tumors. Tumor was defined as a new growth of tissue characterized by progressive, uncontrolled proliferation of cells. In addition, cases presented at 3 major eye pathologic societies (Verhoeff-Zimmerman Ophthalmic Pathology Society, Eastern Ophthalmic Pathology Society, and The Armed Forces Institute of Pathology Ophthalmic Alumni Society) from 1975 through 2014 were reviewed. Finally, a careful search of the literature was carried out. Approval from the institutional review board to carry out this study was obtained. MAIN OUTCOME MEASURES: The presence of tumors of the lens. RESULTS: The database search and literature review failed to find an example of a lens tumor in humans. In contrast, examples of naturally occurring lens tumors were found in cats, dogs, rabbits, and birds. In the veterinary school database, 4.5% of feline intraocular and adnexal neoplasms (234/5153) were designated as feline ocular posttraumatic sarcoma, a tumor previously demonstrated to be of lens epithelial origin. Similar tumors were seen in rabbit eyes, a bird, and in a dog. All 4 species with lens tumors had a history of either ocular trauma or protracted uveitis. The literature search also revealed cases where lens tumors were induced in zebrafish, rainbow trout, hamsters, and mice by carcinogenic agents (methylcholanthrene, thioacetamide), oncogenic viruses (SV40, HPV-16), and genetic manipulation. CONCLUSIONS: Our results suggest that lens tumors do not occur in humans. In contrast, after lens capsule rupture, a lens tumor can occur in other species. We hypothesize that a genetic mechanism exists that prevents lens tumors in humans. PMID- 26130329 TI - Quantitative Intraoperative Torsional Forced Duction Test. AB - PURPOSE: We developed a method for quantifying intraoperative torsional forced ductions and validated the new test by comparing patients with oblique dysfunction and controls. DESIGN: Comparative case series. SUBJECTS: We studied 33 eyes with oblique dysfunction (9 with presumed congenital superior oblique palsy [SOP], 13 with acquired SOP, 7 with Brown syndrome, and 4 with inverted Brown syndrome) and 31 controls. We also studied 6 eyes after superior oblique (SO) disinsertion and 2 eyes after inferior oblique (IO) disinsertion. METHODS: Under deep general anesthesia, the 12 and 6 o'clock positions at the limbus were marked and the globe was maximally excyclorotated and incyclorotated without retroplacement until the first resistance was felt, and the angle of rotation (in degrees) was read on a Mendez ring by the surgeon. A photograph was taken in each position to be read by a masked observer. MAIN OUTCOME MEASURES: Maximal excyclorotation and maximal incyclorotation in each oblique dysfunction and in controls by both surgeon's report and photographic assessment. We duplicated the photographs to evaluate test-retest reliability and to evaluate agreement between the surgeon's assessments and the photographic assessment. RESULTS: Surgeon's assessment revealed greater maximal excyclorotation in eyes with presumed congenital SOP than in controls (median, 40 vs. 30 degrees). Maximal excyclorotation in eyes with acquired SOP was similar to that in controls (30 degrees in both). Eyes with Brown syndrome and inverted Brown syndrome had lower maximal excyclorotation than in controls (10 and 20 vs. 30 degrees, respectively). Maximal incyclorotation in eyes with inverted Brown syndrome was lower than in controls (12.5 vs. 30 degrees), whereas it was similar to that of controls in eyes with presumed congenital SOP, acquired SOP, and Brown syndrome (30 degrees in each condition). Median maximal excyclorotation after SO disinsertion was 62.5 degrees, and maximal incyclorotation after IO disinsertion was 60 degrees. Photographic assessment yielded findings essentially identical to the surgeon's report. Test-retest reliability of the photographic reading was excellent, and agreement between the surgeon's report and the photographic reading was also excellent (95% limits of agreement, 4.4 and 11.6; intraclass correlation coefficient, 0.97 and 0.82, respectively). CONCLUSIONS: The new torsional forced duction test enables quantitative assessment of SO and IO tightness and laxity. PMID- 26130330 TI - The sensing of respiratory gases in fish: Mechanisms and signalling pathways. AB - Chemoreception in fish is critical for sensing changes in the chemical composition of the external and internal environments and is often the first step in a cascade of events leading to cardiorespiratory and metabolic adjustments. Of paramount importance is the ability to sense changes in the levels of the three respiratory gases, oxygen (O2), carbon dioxide (CO2) and ammonia (NH3). In this review, we discuss the role of piscine neuroepithelial cells (NEC), putative peripheral chemoreceptors, as tri-modal sensors of O2, CO2 and NH3. Where possible, we elaborate on the signalling pathways linking NEC stimulation to afferent responses, the potential role of neurotransmitters in activating downstream neuronal pathways and the impact of altered levels of the respiratory gases on NEC structure and function. Although serotonin, the major neurotransmitter contained within NECs, is presumed to be the principal agent eliciting the reflex responses to altered levels of the respiratory gases, there is accumulating evidence for the involvement of "gasomitters", a class of gaseous neurotransmitters which includes nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S). Recent data suggest that CO inhibits and H2S stimulates NEC activity whereas NO can either be inhibitory or stimulatory depending on developmental age. PMID- 26130331 TI - Syria's lost generation of doctors. PMID- 26130332 TI - 'LungGENS': a web-based tool for mapping single-cell gene expression in the developing lung. AB - We developed LungGENS (Lung Gene Expression iN Single-cell), a web-based bioinformatics resource for querying single-cell gene expression databases by entering a gene symbol or a list of genes or selecting a cell type of their interest. Gene query provides quantitative RNA expression of the gene of interest in each lung cell type. Cell type query returns associated selective gene signatures and genes encoding cell surface markers and transcription factors in interactive heatmap and tables. LungGENS will be broadly applicable in respiratory research, providing a cell-specific RNA expression resource at single cell resolution. LungGENS is freely available for non-commercial use at https://research.cchmc.org/pbge/lunggens/default.html. PMID- 26130333 TI - Comparing K-mer based methods for improved classification of 16S sequences. AB - BACKGROUND: The need for precise and stable taxonomic classification is highly relevant in modern microbiology. Parallel to the explosion in the amount of sequence data accessible, there has also been a shift in focus for classification methods. Previously, alignment-based methods were the most applicable tools. Now, methods based on counting K-mers by sliding windows are the most interesting classification approach with respect to both speed and accuracy. Here, we present a systematic comparison on five different K-mer based classification methods for the 16S rRNA gene. The methods differ from each other both in data usage and modelling strategies. We have based our study on the commonly known and well-used naive Bayes classifier from the RDP project, and four other methods were implemented and tested on two different data sets, on full-length sequences as well as fragments of typical read-length. RESULTS: The difference in classification error obtained by the methods seemed to be small, but they were stable and for both data sets tested. The Preprocessed nearest-neighbour (PLSNN) method performed best for full-length 16S rRNA sequences, significantly better than the naive Bayes RDP method. On fragmented sequences the naive Bayes Multinomial method performed best, significantly better than all other methods. For both data sets explored, and on both full-length and fragmented sequences, all the five methods reached an error-plateau. CONCLUSIONS: We conclude that no K mer based method is universally best for classifying both full-length sequences and fragments (reads). All methods approach an error plateau indicating improved training data is needed to improve classification from here. Classification errors occur most frequent for genera with few sequences present. For improving the taxonomy and testing new classification methods, the need for a better and more universal and robust training data set is crucial. PMID- 26130334 TI - Intimate partner violence and substance use risk among young men who have sex with men: The P18 cohort study. AB - OBJECTIVES: Substance use is prevalent among young men who have sex with men (YMSM) and may be associated with intimate partner violence (IPV). Experiences of IPV are associated with several adverse health conditions among adult MSM, but there is a gap in knowledge about this relationship among YMSM, which warrants further investigation. METHODS: This study employs baseline data from a prospective cohort study to examine lifetime experiences of IPV in relation to substance use in the previous 30 days among n=528 YMSM in New York City from 2009 to 2011. To examine the extent to which IPV (any experiences, victimization, and perpetration) are related to substance use (alcohol, marijuana, stimulant, and other drugs) in the last 30 days, distinct 2-step multinomial logistic regression models, controlling for sociodemographic differences, were constructed. RESULTS: 44.3% reported lifetime IPV experience, with 39.2% of reporting victimization and 30.5% reporting perpetration. IPV is associated with a 1.6 increased odds of 2 or more instances of alcohol use, a 1.6-1.8 increased odds of 2 or more instances of marijuana use, a 1.8-2.5 increased odds of 2 or more instances of stimulant use, and a 4.1-6.1 increased odds of 2 or more instances of other substance use. CONCLUSION: Findings highlight the strong association between IPV and increased frequency of substance use among YMSM and provide support that violence may exist as part of a syndemic facing YMSM. Prevention and intervention strategies may be improved by addressing substance use in the context of IPV and other related health challenges. PMID- 26130335 TI - Can differences in the type, nature or amount of polysubstance use explain the increased risk of non-fatal overdose among psychologically distressed people who inject drugs? AB - BACKGROUND: This study investigates whether the type, nature or amount of polysubstance use can explain the increased risk of non-fatal overdose among people who inject drugs with severe psychological distress. METHODS: Data came from three years (2011-2013) of the Illicit Drug Reporting System (IDRS), an annual sentinel sample of injecting drug users across Australia (n=2673). Structural Equation Modelling (SEM) was used on 14 drug types to construct five latent factors, each representing a type of polysubstance use. Tests of measurement invariance were carried out to determine if polysubstance use profiles differed between those with and without severe psychological distress. Next, we regressed non-fatal overdose on the polysubstance use factors with differences in the relationships tested between groups. FINDINGS: Among those with severe psychological distress a polysubstance use profile characterised by heroin, oxycodone, crystal methamphetamine and cocaine use was associated with greater risk of non-fatal overdose. Among those without severe psychological distress, two polysubstance use profiles, largely characterised by opioid substitution therapies and prescription drugs, were protective against non-fatal overdose. CONCLUSION: The types of polysubstance use profiles did not differ between people who inject drugs with and without severe psychological distress. However, the nature of use of one particular polysubstance profile placed the former group at a strongly increased risk of non-fatal overdose, while the nature of polysubstance use involving opioid substitution therapies was protective only among the latter group. The findings identify polysubstance use profiles of importance to drug-related harms among individuals with psychological problems. PMID- 26130337 TI - What are the key drivers that change practice? PMID- 26130336 TI - Identification of smokers, drinkers and risky drinkers by general practitioners. AB - BACKGROUND: Identification of risky substance users by general practitioners (GPs) is important for providing brief interventions or to refer cases to specialized care, but detection rates of risky users are low, with alcohol users being identified less frequently than smokers. METHODS: We compared GPs' assessment and patient self-report concerning tobacco use, number of cigarettes smoked daily, alcohol use, alcohol use disorder, and different risky use definitions of 8476 primary care patients from six European countries. Further, we carried out a logistic regression predicting the GPs perception of the patients' alcohol problems. RESULTS: GPs identified 88.4% (95% confidence interval (CI): 87.1-89.6%; kappa=0.84, 95% CI: 0.83-0.86) of all self-reported smokers but only 64.6% (95% CI: 63.2-65.9%; kappa=0.35, 95% CI: 0.33-0.37) of all current drinkers, while they were unable to judge the drinking status of every ninth patient. The GPs' estimation of number of cigarettes smoked daily was slightly lower than the self-report (Delta=0.23 cigarettes/day, p<.001) but both measures were correlated with each other. Of all risky drinkers, defined as having alcohol-related problems or showing risky drinking patterns, 28.7% (95% CI: 25.9-31.4%; kappa=0.34, 95% CI: 0.31-0.37) were perceived as having problems with alcohol by the GPs. Patients' self-reported health and social consequences, as well as drinking patterns predicted the GPs' perception of alcohol problems. CONCLUSIONS: GPs were more accurate in identifying smokers than drinkers. Concerning risky drinkers, GPs failed to diagnose a sizeable proportion but were able to detect other drinkers whom common recognition approaches had not recognized. PMID- 26130338 TI - Should we all go to the PROM? The first two years of the British Spine Registry. AB - The effective capture of outcome measures in the healthcare setting can be traced back to Florence Nightingale's investigation of the in-patient mortality of soldiers wounded in the Crimean war in the 1850s. Only relatively recently has the formalised collection of outcomes data into Registries been recognised as valuable in itself. With the advent of surgeon league tables and a move towards value based health care, individuals are being driven to collect, store and interpret data. Following the success of the National Joint Registry, the British Association of Spine Surgeons instituted the British Spine Registry. Since its launch in 2012, over 650 users representing the whole surgical team have registered and during this time, more than 27 000 patients have been entered onto the database. There has been significant publicity regarding the collection of outcome measures after surgery, including patient-reported scores. Over 12 000 forms have been directly entered by patients themselves, with many more entered by the surgical teams. Questions abound: who should have access to the data produced by the Registry and how should they use it? How should the results be reported and in what forum? PMID- 26130339 TI - Hip fracture surgery: improving the quality of the evidence base. AB - Hip fracture is a common injury associated with high mortality, long-term disability and huge socio-economic burden. Yet there has been relatively little research into best treatment, and evidence that has been generated has often been criticised for its poor quality. Here, we discuss the advances made towards overcoming these criticisms and the future directions for hip fracture research: how co-ordinating existing national infrastructures and use of now established clinical research networks will likely go some way towards overcoming the practical and financial challenges of conducting large trials. We highlight the importance of large collaborative pragmatic trials to inform decision/policy makers and the progress made towards reaching a consensus on a core outcome set to facilitate data pooling for evidence synthesis and meta-analysis. These advances and future directions are a priority in order to establish the high quality evidence base required for this important group of patients. PMID- 26130340 TI - Calcaneal fractures: selection bias is key. AB - In this paper, we critically appraise the recent publication of the United Kingdom Heel Fracture Trial, which concluded that when patients with an absolute indication for surgery were excluded, there was no advantage of surgical over non surgical treatment in the management of calcaneal fractures. We believe that selection bias in that study did not permit the authors to reach a firm conclusion that surgery was not justified for most intra-articular calcaneal fractures. PMID- 26130341 TI - Five-year comparison of wear using oxidised zirconium and cobalt-chrome femoral heads in total hip arthroplasty: a multicentre randomised controlled trial. AB - Oxidised zirconium (OxZi) has been developed as an alternative bearing surface for femoral heads in total hip arthroplasty (THA). This study has investigated polyethylene wear, functional outcomes and complications, comparing OxZi and cobalt-chrome (CoCr) as part of a three-arm, multicentre randomised controlled trial. Patients undergoing THA from four institutions were prospectively randomised into three groups. Group A received a CoCr femoral head and highly cross-linked polyethylene (XLPE) liner; Group B received an OxZi femoral head and XLPE liner; Group C received an OxZi femoral head and ultra-high molecular weight polyethylene (UHMWPE) liner. At five years, 368 patients had no statistically significant differences in short-form-36 (p = 0.176 mental, p = 0.756 physical), Western Ontario and McMaster Universities Osteoarthritis Index (p = 0.847), pain scores (p = 0.458) or complications. The mean rate of linear wear was 0.028 mm/year (standard deviation (SD) 0.010) for Group A, 0.023 mm/year (SD 0.010) for Group B, and 0.09 mm/year (SD 0.045) for Group C. Penetration was significantly higher in the UHMWPE liner group compared with both XLPE liner groups (p < 0.001) but no significant difference was noted between CoCr and OxZi when articulating with XLPE (p = 0.153). In this, the largest randomised study of this bearing surface, it appears that using a XLPE acetabular liner is more important in reducing THA component wear than the choice of femoral head bearing, at mid-term follow-up. There is a non-significant trend towards lower wear, coupling OxZi rather than CoCr with XLPE but long-term analysis is required to see if this observation changes with time and becomes significant. PMID- 26130342 TI - Impingement-free range of movement, acetabular component cover and early clinical results comparing 'femur-first' navigation and 'conventional' minimally invasive total hip arthroplasty: a randomised controlled trial. AB - We report the kinematic and early clinical results of a patient- and observer blinded randomised controlled trial in which CT scans were used to compare potential impingement-free range of movement (ROM) and acetabular component cover between patients treated with either the navigated 'femur-first' total hip arthroplasty (THA) method (n = 66; male/female 29/37, mean age 62.5 years; 50 to 74) or conventional THA (n = 69; male/female 35/34, mean age 62.9 years; 50 to 75). The Hip Osteoarthritis Outcome Score, the Harris hip score, the Euro-Qol-5D and the Mancuso THA patient expectations score were assessed at six weeks, six months and one year after surgery. A total of 48 of the patients (84%) in the navigated 'femur-first' group and 43 (65%) in the conventional group reached all the desirable potential ROM boundaries without prosthetic impingement for activities of daily living (ADL) in flexion, extension, abduction, adduction and rotation (p = 0.016). Acetabular component cover and surface contact with the host bone were > 87% in both groups. There was a significant difference between the navigated and the conventional groups' Harris hip scores six weeks after surgery (p = 0.010). There were no significant differences with respect to any clinical outcome at six months and one year of follow-up. The navigated 'femur first' technique improves the potential ROM for ADL without prosthetic impingement, although there was no observed clinical difference between the two treatment groups. PMID- 26130343 TI - A new classification of peri-articular heterotopic ossification of the hip associated with neurological injury: 3D CT scan assessment and intra-operative findings. AB - In this paper we propose a new classification of neurogenic peri-articular heterotopic ossification (HO) of the hip based on three-dimensional (3D) CT, with the aim of improving pre-operative planning for its excision. A total of 55 patients (73 hips) with clinically significant HO after either traumatic brain or spinal cord injury were assessed by 3D-CT scanning, and the results compared with the intra-operative findings. At operation, the gross pathological anatomy of the HO as identified by 3D-CT imaging was confirmed as affecting the peri-articular hip muscles to a greater or lesser extent. We identified seven patterns of involvement: four basic (anterior, medial, posterior and lateral) and three mixed (anteromedial, posterolateral and circumferential). Excellent intra- and inter observer agreement, with kappa values > 0.8, confirmed the reproducibility of the classification system. We describe the different surgical approaches used to excise the HO which were guided by the 3D-CT findings. Resection was always successful. 3D-CT imaging, complemented in some cases by angiography, allows the surgeon to define the 3D anatomy of the HO accurately and to plan its surgical excision with precision. PMID- 26130344 TI - A regime of two intravenous injections of tranexamic acid reduces blood loss in minimally invasive total hip arthroplasty: a prospective randomised double-blind study. AB - Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA. In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism. The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications. This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA. PMID- 26130345 TI - Taperosis: Does head length affect fretting and corrosion in total hip arthroplasty? AB - Tribocorrosion at the head-neck taper interface - so-called 'taperosis' - may be a source of metal ions and particulate debris in metal-on-polyethylene total hip arthroplasty (THA). We examined the effect of femoral head length on fretting and corrosion in retrieved head-neck tapers in vivo for a minimum of two years (mean 8.7 years; 2.6 to 15.9). A total of 56 femoral heads ranging from 28 mm to 3 mm to 28 mm + 8 mm, and 17 femoral stems featuring a single taper design were included in the study. Fretting and corrosion were scored in three horizontally oriented concentric zones of each taper by stereomicroscopy. Head length was observed to affect fretting (p = 0.03), with 28 mm + 8 mm femoral heads showing greater total fretting scores than all other head lengths. The central zone of the femoral head bore taper was subject to increased fretting damage (p = 0.01), regardless of head length or stem offset. High-offset femoral stems were associated with greater total fretting of the bore taper (p = 0.04). Increased fretting damage is seen with longer head lengths and high-offset femoral stems, and occurs within a central concentric zone of the femoral head bore taper. Further investigation is required to determine the effect of increased head size, and variations in head-neck taper design. PMID- 26130346 TI - Particle characterisation and cytokine expression in failed small-diameter metal on-metal total hip arthroplasties. AB - The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the 'biologically active area' of all metal wear particles may predict the type of peri-prosthetic tissue response. Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). The overall distribution of the size and area of the particles in both lymphocyte and non lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. 14 cytokines (interleukin (IL)-1beta, IL-2, IL-4, IL 5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-gamma, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1alpha and MIP 1beta), and growth factors (granulocyte macrophage colony stimulating factor (GM CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. Significantly higher levels for IL-1beta, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri prosthetic response compared with those without this response. These results suggest that the 'biologically active area' predicts the type of peri-prosthetic tissue response. The cytokines IL-1beta, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA. PMID- 26130347 TI - A placebo-controlled randomised trial to assess the effect of TGF-beta1 expressing chondrocytes in patients with arthritis of the knee. AB - The aim of this study was to assess the effect of injecting genetically engineered chondrocytes expressing transforming growth factor beta 1 (TGF-beta1) into the knees of patients with osteoarthritis. We assessed the resultant function, pain and quality of life. A total of 54 patients (20 men, 34 women) who had a mean age of 58 years (50 to 66) were blinded and randomised (1:1) to receive a single injection of the active treatment or a placebo. We assessed post treatment function, pain severity, physical function, quality of life and the incidence of treatment-associated adverse events. Patients were followed at four, 12 and 24 weeks after injection. At final follow-up the treatment group had a significantly greater improvement in the mean International Knee Documentation Committee score than the placebo group (16 points; -18 to 49, vs 8 points; -4 to 37, respectively; p = 0.03). The treatment group also had a significantly improved mean visual analogue score at final follow-up (-25; -85 to 34, vs -11 points; -51 to 25, respectively; p = 0.032). Both cohorts showed an improvement in Western Ontario and McMaster Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome Scores, but these differences were not statistically significant. One patient had an anaphylactic reaction to the preservation medium, but recovered within 24 hours. All other adverse events were localised and resolved without further action. This technique may result in improved clinical outcomes, with the aim of slowing the degenerative process, leading to improvements in pain and function. However, imaging and direct observational studies are needed to verify cartilage regeneration. Nevertheless, this study provided a sufficient basis to proceed to further clinical testing. PMID- 26130348 TI - The viability of chondrocytes after an in vivo injection of local anaesthetic and/or corticosteroid: a laboratory study using a rat model. AB - This in vivo controlled laboratory study was performed to evaluate various intra articular clinical injection regimes that might be less toxic than some in vitro studies suggest. We hypothesised that low-concentration, preservative-free, pH balanced agents would be less toxic than high-concentration non-pH-balanced agents with preservatives, and that injections of individual agents are less toxic than combined injections. The left knees of 12- to 13-week-old Sprague Dawley rats were injected once with eight different single agents, including low and high concentrations of ropivacaine and triamcinolone, alone and in combination, as well as negative and positive controls. The rats were killed at one week or five months, and live-dead staining was performed to quantify the death of chondrocytes. All injections except pH-balanced 0.2% ropivacaine combined with preservative-free 1 mg/ml triamcinolone acetonide resulted in statistically significant decreases in chondrocyte viability, compared with control knees, after one week and five months (p < 0.001). After one week there was no significant difference in viability between 0.2% and 0.5% ropivacaine; however, 4 mg/ml triamcinolone resulted in a lower viability than 1 mg/ml triamcinolone. Although many agents commonly injected into joints are chondrotoxic, in this in vivo study diluting preservative-free 10 mg/ml triamcinolone 1:9 in 0.2% pH-balanced ropivacaine resulted in low toxicity. PMID- 26130349 TI - Seronegative infections in hip and knee arthroplasty: periprosthetic infections with normal erythrocyte sedimentation rate and C-reactive protein level. AB - The aim of our study was to describe the characteristics, treatment, and outcomes of patients with periprosthetic joint infection (PJI) and normal inflammatory markers after total knee arthroplasty (TKA) and total hip arthroplasty (THA). In total 538 TKAs and 414 THAs underwent surgical treatment for PJI and met the inclusion criteria. Pre-operative erythrocyte sedimentation rate (ESR) and C reactive protein level (CRP) were reviewed to identify the seronegative cohort. An age- and gender-matched cohort was identified from the remaining patients for comparison. Overall, 4% of confirmed infections were seronegative (21 TKA and 17 THA). Of those who underwent pre-operative aspiration, cultures were positive in 76% of TKAs (n = 13) and 64% of THAs (n = 7). Cell count and differential were suggestive of infection in 85% of TKA (n = 11) and all THA aspirates (n = 5). The most common organism was coagulase-negative Staphylococcus. Seronegative infections were associated with a lower aspirate cell count and a lower incidence of Staphylococcus aureus infection. Two-stage revision was performed in 35 cases (95%). At a mean of five years (14 to 162 months) following revision, re operation for infection occurred in two TKAs, and one THA. From our study we estimate around 4% of patients with PJI may present with normal ESR and CRP. When performed, pre-operative aspirate is useful in delivering a definitive diagnosis. When treated, similar outcomes can be obtained compared with patients with positive serology. PMID- 26130350 TI - Incidence and clinical relevance of tibiofibular synostosis in fractures of the ankle which have been treated surgically. AB - In this retrospective cohort study, we analysed the incidence and functional outcome of a distal tibiofibular synostosis. Patients with an isolated AO type 44 B or C fracture of the ankle who underwent surgical treatment between 1995 and 2007 were invited for clinical and radiological review. The American Orthopaedic Foot and Ankle Society score, the American Academy of Orthopaedic Surgeons score and a visual analogue score for pain were used to assess outcome. A total of 274 patients were available; the mean follow-up was 9.7 years (8 to 18). The extent of any calcification or synostosis at the level of the distal interosseous membrane or syndesmosis on the contemporary radiographs was defined as: no or minor calcifications (group 1), severe calcification (group 2), or complete synostosis (group 3). A total of 222 (81%) patients were in group 1, 37 (14%) in group 2 and 15 (5%) in group 3. There was no significant difference in incidence between AO type 44-B and type 44-C fractures (p = 0.89). Severe calcification or synostosis occurred in 21 patients (19%) in whom a syndesmotic screw was used and in 31 (19%) in whom a syndesmotic screw was not used.(p = 0.70). No significant differences were found between the groups except for a greater reduction in mean dorsiflexion in group 2 (p = 0.004). This is the largest study on distal tibiofibular synostosis, and we found that a synostosis is a frequent complication of surgery for a fracture of the ankle. Although it theoretically impairs the range of movement of the ankle, it did not affect the outcome. Our findings suggest that synostosis of the distal tibiofibular syndesmosis in general does not warrant treatment. PMID- 26130351 TI - Functional and radiological outcome of periprosthetic fractures of the ankle. AB - The incidence of periprosthetic fractures of the ankle is increasing. However, little is known about the outcome of treatment and their management remains controversial. The aim of this study was to assess the impact of periprosthetic fractures on the functional and radiological outcome of patients with a total ankle arthroplasty (TAA). A total of 505 TAAs (488 patients) who underwent TAA were retrospectively evaluated for periprosthetic ankle fracture: these were then classified according to a recent classification which is orientated towards treatment. The outcome was evaluated clinically using the American Orthopedic Foot and Ankle Society (AOFAS) score and a visual analogue scale for pain, and radiologically. A total of 21 patients with a periprosthetic fracture of the ankle were identified. There were 13 women and eight men. The mean age of the patients was 63 years (48 to 74). Thus, the incidence of fracture was 4.17%. There were 11 intra-operative and ten post-operative fractures, of which eight were stress fractures and two were traumatic. The prosthesis was stable in all patients. Five stress fractures were treated conservatively and the remaining three were treated operatively. A total of 17 patients (81%) were examined clinically and radiologically at a mean follow-up of 53.5 months (12 to 112). The mean AOFAS score at follow-up was 79.5 (21 to 100). The mean AOFAS score in those with an intra-operative fracture was 87.6 (80 to 100) and for those with a stress fracture, which were mainly because of varus malpositioning, was 67.3 (21 to 93). Periprosthetic fractures of the ankle do not necessarily adversely affect the clinical outcome, provided that a treatment algorithm is implemented with the help of a new classification system. PMID- 26130352 TI - Arthroscopic assistance does not improve the functional or radiographic outcome of unstable intra-articular distal radial fractures treated with a volar locking plate: a randomised controlled trial. AB - There is no consensus on the benefit of arthroscopically assisted reduction of the articular surface combined with fixation using a volar locking plate for the treatment of intra-articular distal radial fractures. In this study we compared the functional and radiographic outcomes of fluoroscopically and arthroscopically guided reduction of these fractures. Between February 2009 and May 2013, 74 patients with unilateral unstable intra-articular distal radial fractures were randomised equally into the two groups for treatment. The mean age of these 74 patients was 64 years (24 to 92). We compared functional outcomes including active range of movement of the wrist, grip strength and Disabilities of the Arm, Shoulder, and Hand scores at six and 48 weeks; and radiographic outcomes that included gap, step, radial inclination, volar angulation and ulnar variance. There were no significant differences between the techniques with regard to functional outcomes or radiographic parameters. The mean gap and step in the fluoroscopic and arthroscopic groups were comparable at 0.9 mm (standard deviation (SD) 0.7) and 0.7 mm (SD 0.7) and 0.6 mm (SD 0.6) and 0.4 mm (SD 0.5), respectively; p = 0.18 and p = 0.35). Arthroscopic reduction conferred no advantage over conventional fluoroscopic guidance in achieving anatomical reduction of intra-articular distal radial fractures when using a volar locking plate. PMID- 26130353 TI - Frozen shoulder after simple arthroscopic shoulder procedures: What is the risk? AB - Frozen shoulder is a recognised complication following simple arthroscopic shoulder procedures, but its exact incidence has not been reported. Our aim was to analyse a single-surgeon series of patients undergoing arthroscopic subacromial decompression (ASD; group 1) or ASD in combination with arthroscopic acromioclavicular joint (ACJ) excision (group 2), to establish the incidence of frozen shoulder post-operatively. Our secondary aim was to identify associated risk factors and to compare this cohort with a group of patients with primary frozen shoulder. We undertook a retrospective analysis of 200 consecutive procedures performed between August 2011 and November 2013. Group 1 included 96 procedures and group 2 104 procedures. Frozen shoulder was diagnosed post operatively using the British Elbow and Shoulder Society criteria. A comparative group from the same institution involved 136 patients undergoing arthroscopic capsular release for primary idiopathic frozen shoulder. The incidence of frozen shoulder was 5.21% in group 1 and 5.71% in group 2. Age between 46 and 60 years (p = 0.002) and a previous idiopathic contralateral frozen shoulder (p < 0.001) were statistically significant risk factors for the development of secondary frozen shoulder. Comparison of baseline characteristics against the comparator groups showed no statistically significant differences for age, gender, diabetes and previous contralateral frozen shoulder. These results suggest that the risk of frozen shoulder following simple arthroscopic procedures is just over 5%, with no increased risk if the ACJ is also excised. Patients aged between 46 and 60 years and a previous history of frozen shoulder increase the relative risk of secondary frozen shoulder by 7.8 (95% confidence interval (CI) 2.1 to 28.3)and 18.5 (95% CI 7.4 to 46.3) respectively. PMID- 26130354 TI - Reverse shoulder arthroplasty as a salvage procedure after failed internal fixation of fractures of the proximal humerus: outcomes and complications. AB - Failed internal fixation of a fracture of the proximal humerus produces many challenges with limited surgical options. The aim of this study was to evaluate the clinical outcomes after the use of a reverse shoulder arthroplasty under these circumstances. Between 2007 and 2012, 19 patients (15 women and four men, mean age 66 years; 52 to 82) with failed internal fixation after a proximal humeral fracture, underwent implant removal and reverse shoulder arthroplasty (RSA). The mean follow-up was 36 months (25 to 60). The mean American Shoulder and Elbow Score improved from 27.8 to 50.1 (p = 0.019). The mean Simple Shoulder Test score improved from 0.7 to 3.2 (p = 0.020), and the mean visual analogue scale for pain improved from 6.8 to 4.3 (p = 0.012). Mean forward flexion improved from 58.7 degrees to 101.1 degrees (p < 0.001), mean abduction from 58.7 degrees to 89.1 degrees (p = 0.012), mean external rotation from 10.7 degrees to 23.1 degrees (p = 0.043) and mean internal rotation from buttocks to L4 (p = 0.034). A major complication was recorded in five patients (26%) (one intra-operative fracture, loosening of the humeral component in two and two peri prosthetic fractures). A total of 15 patients (79%) rated their outcome as excellent or good, one (5%) as satisfactory, and three (16%) as unsatisfactory. An improvement in outcomes and pain can be expected when performing a RSA as a salvage procedure after failed internal fixation of a fracture of the proximal humerus. Patients should be cautioned about the possibility for major complications following this technically demanding procedure. PMID- 26130355 TI - An alternative to a randomised control design for assessing the efficacy and effectiveness of bracing in adolescent idiopathic scoliosis. AB - Randomised controlled trials (RCTs) that assessed the efficacy of bracing for adolescent idiopathic scoliosis have suffered from small sample sizes, low compliance and lack of willingness to participate. The aim of this study was to assess the feasibility of a comprehensive cohort study for evaluating both the efficacy and the effectiveness of bracing in patients with adolescent idiopathic scoliosis. Patients with curves at greater risk of progression were invited to join a randomised controlled trial. Those who declined were given the option to remain in the study and to choose whether they wished to be braced or observed. Of 87 eligible patients (5 boys and 63 girls) identified over one year, 68 (78%) with mean age of 12.5 years (10 to 15) consented to participate, with a mean follow-up of 168 weeks (0 to 290). Of these, 19 (28%) accepted randomisation. Of those who declined randomisation, 18 (37%) chose a brace. Patients who were more satisfied with their image were more likely to choose bracing (Odds Ratio 4.1; 95% confidence interval 1.1 to 15.0; p = 0.035). This comprehensive cohort study design facilitates the assessment of both efficacy and effectiveness of bracing in patients with adolescent idiopathic scoliosis, which is not feasible in a conventional randomised controlled trial. PMID- 26130356 TI - Infantile developmental thoracolumbar kyphosis with segmental subluxation of the spine: report of five patients and review of the literature. AB - Acute angulation at the thoracolumbar junction with segmental subluxation of the spine occurring at the level above an anteriorly hypoplastic vertebra in otherwise normal children is a rare condition described as infantile developmental thoracolumbar kyphosis. Three patient series with total of 18 children have been reported in the literature. We report five children who presented with thoracolumbar kyphosis and discuss the treatment algorithm. We reviewed the medical records and spinal imaging at initial clinical presentation and at minimum two-year follow-up. The mean age at presentation was eight months (two to 12). All five children had L2 anterior vertebral body hypoplasia. The kyphosis improved spontaneously in three children kept under monitoring. In contrast, the deformity was progressive in two patients who were treated with bracing. The kyphosis and segmental subluxation corrected at latest follow-up (mean age 52 months; 48 to 60) in all patients with near complete reconstitution of the anomalous vertebra. The deformity and radiological imaging on a young child can cause anxiety to both parents and treating physicians. Diagnostic workup and treatment algorithm in the management of infantile developmental thoracolumbar kyphosis is proposed. Observation is indicated for non-progressive kyphosis and bracing if there is evidence of kyphosis and segmental subluxation deterioration beyond walking age. Surgical stabilisation of the spine can be reserved for severe progressive deformities unresponsive to conservative treatment. PMID- 26130357 TI - Salvage of failed osteosynthesis of an intracapsular fracture of the femoral neck using two cannulated compression screws and a vascularised iliac crest bone graft. AB - We evaluated the outcome of treatment of nonunion of an intracapsular fracture of the femoral neck in young patients using two cannulated screws and a vascularised bone graft. A total of 32 patients (15 women and 17 men, with a mean age of 36.5 years; 20 to 50) with failed internal fixation of an intracapsular fracture were included in the study. Following removal of the primary fixation, two cannulated compression screws were inserted with a vascularised iliac crest bone graft based on the ascending branch of the lateral femoral circumflex artery. At a mean follow-up of 6.8 years (4 to 10), union was achieved in 27 hips (84%). A total of five patients with a mean age of 40.5 years (35 to 50) had a persistent nonunion and underwent total hip arthroplasty as also did two patients whose fracture united but who developed osteonecrosis of the femoral head two years post operatively. Statistical analysis showed that younger patients achieved earlier and more reliable union (p < 0.001). The functional outcome, as assessed by the Harris Hip score, was better in patients aged < 45 years compared with those aged > 45 years (p < 0.001). These findings suggest that further fixation using two cannulated compression screws and a vascularised iliac crest bone graft is an effective salvage treatment in patients aged < 45 years, in whom osteosynthesis of a displaced intracapsular fractures of the femoral neck has failed. PMID- 26130358 TI - Hemiarthroplasty versus internal fixation for displaced intracapsular fractures of the hip in elderly men: a pilot randomised trial. AB - A total of 56 male patients with a displaced intracapsular fracture of the hip and a mean age of 81 years (62 to 94), were randomised to be treated with either a cemented hemiarthroplasty (the Exeter Trauma Stem) or reduction and internal fixation using the Targon Femoral Plate. All surviving patients were reviewed one year after the injury, at which time restoration of function and pain in the hip was assessed. There was no statistically significant difference in mortality between the two groups (7/26; 26.9% for hemiarthroplasty vs 10/30; 33.3% for internal fixation). No patient treated with a hemiarthroplasty required further surgery, but eight patients treated by internal fixation did (p = 0.005), five requiring hemiarthroplasty and three requiring total hip arthroplasty. Those treated by internal fixation had significantly more pain (p = 0.02). The restoration of mobility and independence were similar in the two groups. These results indicate that cemented hemiarthroplasty gives better results than internal fixation in elderly men with a displaced intracapsular fracture of the hip. PMID- 26130359 TI - RhBMP-7 for the treatment of nonunion of fractures of long bones. AB - We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients' quality of life was estimated using the Short Form (SF) 12 score. A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year. Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union. PMID- 26130360 TI - Long-term patient-reported outcomes following Bennett's fractures. AB - We define the long-term outcomes and rates of further operative intervention following displaced Bennett's fractures treated with Kirschner (K-) wire fixation between 1996 and 2009. We retrospectively identified 143 patients (127 men and 16 women) with a mean age at the time of injury of 33.2 years (18 to 75). Electronic records were examined and patients were invited to complete the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire in addition to a satisfaction questionnaire. The time since injury was a mean of 11.5 years (3.4 to 18.5). In total 11 patients had died, one had developed dementia and 12 patients were lost to follow-up. This left 119 patients available for recruitment. Of these, 57 did not respond, leaving a study group of 62 patients. Patients reported excellent functional outcomes and high levels of satisfaction at follow-up. Median satisfaction was 94% (interquartile range 91.5 to 97.5) and the mean DASH score was 3.0 (0 to 38). None of the patients had undergone salvage procedures and none of the responders had changed occupation or sporting activities. Long-term patient reported outcomes following displaced Bennett's fractures treated by closed reduction and K-wire fixation show excellent functional results and a high level of patient satisfaction. The rate of infection is low and similar to other surgical procedures with percutaneous K-wires. PMID- 26130361 TI - Osteoarthritis of the hip in fibrous dysplasia of the proximal femur. AB - Deformity of the proximal femur in fibrous dysplasia leads to deviation of the mechanical axis of the hip, which may lead to the development of secondary osteoarthritis (OA). This study investigated the prevalence and predisposing factors for the development of OA in patients with fibrous dysplasia of the proximal femur. We reviewed the records of 209 patients from our institutional database with fibrous dysplasia of the proximal femur, investigating possible predisposing factors including patient demographics, the extent of the coxa vara deformity, the presence of peri-articular disease, and the overall burden of skeletal disease. Of the 209 patients, 24 (12%) had radiological evidence of OA in the ipsilateral hip. The prevalence was significantly higher in patients with polyostotic fibrous dysplasia compared with those with monostotic disease (p < 0.001). In a subgroup analysis of patients with polyostotic disease, the extent of deformity (quantified using the neck-shaft angle), and the presence of peri articular disease (whether in the head of the femur or the acetabulum) were significant predictors of osteoarthritis (neck-shaft angle likelihood ratio (LR) = 0.847 per 1 degrees increase, p = 0.004; presence of lesion in the head of the femur LR = 9.947, p = 0.027; presence of lesion in the acetabulum LR = 11.231, p = 0.014). Our data suggest that patients with polyostotic fibrous dysplasia have a high risk of developing secondary OA of the hips. This risk is higher in patients with peri-articular disease, and those with a more severe deformity of proximal femur. PMID- 26130362 TI - Errata. PMID- 26130363 TI - Effect of passion fruit seed meal on growth performance, carcass, and blood characteristics in starter pigs. AB - Two experiments were carried out in Parana State, Brazil, to evaluate the nutritional value of passion fruit seed meal (PFM) and to study the effect of PFM on growth performance, carcass, and blood characteristics in starter pigs (Topigs 20 * Tybor). In experiment 1, 25 castrated males, averaging 19.1-kg body weight, were individually fed in a completely randomized block design, consisting of five treatments and five replicates and an experimental period that lasted 14 days. In experiment 2, a total of 60 pigs (30 females and 30 castrated males) were distributed in a randomized block design with five treatments, six replications, and two animals per experimental unit and 90 days of experimentation. For both experiments, the same PFM inclusion rates were used in the experimental diets, namely, 0, 4, 8, 12, and 16 %. The metabolizable energy of PFM was estimated to be 15.0 MJ/kg. Inclusion of PFM at any level did not affect average daily gain, daily feed intake, feed/gain ratio, backfat thickness, loin depth, and plasma or blood components. It is concluded that passion fruit seed meal for swine in the starting phase can be added at a rate of up to 16 % in the diet without any negative effects on growth performance, carcass, and blood characteristics in starter commercial line pigs. PMID- 26130364 TI - Relationship between sleep problems and psychological outcomes in adolescent and young adult cancer survivors and controls. AB - PURPOSE: How cancer history and distress relate to sleep outcomes of adolescents and young adults (AYAs) is unclear. The current study compares AYA cancer survivors to controls on indicators of sleep and fatigue; examines the concurrent association between psychological status, sleep, and fatigue; and investigates the lagged relationship between sleep and fatigue problems with psychological functioning. METHODS: AYA cancer survivors (n = 167) and controls (n = 170), ages 16 to 30, completed measures at a survivorship clinic/primary care visit (time 1) and 2 months later (time 2). Participants completed questions about sleep quality, quantity, sleep medication use, self-reports of sleep problems, and fatigue in addition to measures of depression, anxiety, and posttraumatic stress symptoms (PTSS). RESULTS: There were no differences in sleep quantity or quality between survivors and controls, but survivors reported significantly more fatigue. Within groups, AYAs with self-reported sleep and fatigue problems reported significantly higher depression, anxiety, and PTS symptoms. Controlling for baseline depression, sleep, and fatigue problems at time 1 significantly predicted depression at time 2 in survivors but not in controls. CONCLUSION: This study offers important insight into the psychological functioning of childhood cancer survivors and prospectively describes sleep and fatigue as risk factors for poor psychological functioning in survivors. These findings support screening for sleep problems in AYA survivors as these difficulties are closely related to mental health functioning. PMID- 26130366 TI - Is weekend discharge associated with hospital readmission? AB - BACKGROUND: Although recent evidence suggests worse outcomes for patients admitted to the hospital on a weekend, the impact of weekend discharge is less understood. METHODS: Utilizing the 2012 California Office of Statewide Health Planning and Development database, the impact of weekend discharge on 30-day hospital readmission rates for patients admitted with acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia (PNA) was investigated. RESULTS: Out of 266,519 patients, 60,097 (22.5%) were discharged on a weekend. Unadjusted 30-day hospital readmission rates were similar between weekend and weekday discharges (AMI: 21.9% vs 21.9%; CHF: 15.4% vs 16.0%; PNA: 12.1% vs 12.4%). Patients discharged on a weekday had a longer length of stay and were more often discharged to a skilled nursing facility. However, in multivariable logistic regression models, weekend discharge was not associated with readmission (AMI: odds ratio [OR] 1.02 [95% CI: 0.98-1.06]; CHF: OR 0.99 [95% CI: 0.94-1.03]; PNA: OR 1.02 (95% CI: 0.98-1.07)). CONCLUSIONS: Among patients in California with AMI, CHF, and PNA, discharge on a weekend was not associated with an increased hospital readmission rate. PMID- 26130365 TI - Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial. AB - PURPOSE: Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC. METHODS: This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naive gynecological cancer patients receiving HEC with cisplatin (>=50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy. RESULTS: Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events. CONCLUSIONS: Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy. PMID- 26130367 TI - Iterative image reconstruction for limited-angle inverse helical cone-beam computed tomography. AB - Helical trajectory satisfying the condition of exact reconstruction, has been widely utilized in the commercial computed tomography (CT). While limited by the scanning environment in some practical applications, the conventional helical cone-beam CT imaging is hard to complete, thus, developing an imaging system suited for long-object may be valuable. Three-dimensional C-arm CT is an innovative imaging technique which has been greatly concerned. Since there is a high degree of freedom of C-arm, more flexible image acquisition trajectories for 3D imaging can be achieved. In this work, a fast iterative reconstruction algorithm based on total variation minimization is developed for a trajectory of limited-angle inverse helical cone-beam CT, which can be applied to detect long object without slip-ring technology. The experimental results show that the developed algorithm can yield reconstructed images of low noise level and high image quality. PMID- 26130368 TI - Enhancing efficiency and quality of statistical estimation of immunogenicity assay cut points through standardization and automation. AB - Biotherapeutics can elicit immune responses, which can alter the exposure, safety, and efficacy of the therapeutics. A well-designed and robust bioanalytical method is critical for the detection and characterization of relevant anti-drug antibody (ADA) and the success of an immunogenicity study. As a fundamental criterion in immunogenicity testing, assay cut points need to be statistically established with a risk-based approach to reduce subjectivity. This manuscript describes the development of a validated, web-based, multi-tier customized assay statistical tool (CAST) for assessing cut points of ADA assays. The tool provides an intuitive web interface that allows users to import experimental data generated from a standardized experimental design, select the assay factors, run the standardized analysis algorithms, and generate tables, figures, and listings (TFL). It allows bioanalytical scientists to perform complex statistical analysis at a click of the button to produce reliable assay parameters in support of immunogenicity studies. PMID- 26130369 TI - Roux-en-Y gastric bypass stimulates hypothalamic miR-122 and inhibits cardiac and hepatic miR-122 expressions. AB - BACKGROUND: MicroRNAs (miRNAs) are endogenous noncoding small ribonucleic acids that have emerged as one of the central players of gene expression regulation. This study was designed to determine and identify miRNAs that are associated with Roux-en-Y gastric bypass (RYGB). METHODS: Male Sprague-Dawley rats were divided into two groups: sham and RYGB. Changes in food intake and body weight were measured. miRNA microarray analyses on the brain hypothalamus and heart were performed. The expressions of miR-122 were analyzed, and the activities of adenosine monophosphate-activated protein kinase (AMPK) were determined in the hypothalamus, heart, and liver. Antisense oligonucleotide miR-122 was transfected into hepatocellular carcinoma cells to validate in vivo results. RESULTS: Body weights decreased in the RYGB group compared with those in sham group. Food intake was different between sham and RYGB groups. Of 350 miRNAs that were investigated, we observed that miR-122, being predominantly found in the liver, markedly increased (>35-fold) in the hypothalamus and decreased (>4-fold) in the heart. Quantitative polymerase chain reaction analysis revealed that expression of miR-122 was induced in hypothalamus but attenuated in the heart and liver of the RYGB group. Activities of AMPK were decreased in the hypothalamus but increased in the heart and liver. Knockdown of miR-122 in hepatocellular carcinoma cells stimulated phosphorylation levels AMPK. CONCLUSIONS: The results in this study suggest that RYGB regulates the expressions of miR-122 in the hypothalamus, heart, and liver, which in turn may modulate the activities of AMPK, the master regulator of metabolism. PMID- 26130370 TI - Lentivirus transduced interleukin-1 receptor antagonist gene expression in murine bone marrow-derived mesenchymal stem cells in vitro. AB - Genetically modified mesenchymal stem cells have been used in attempts to increase the expression of interleukin-1 receptor antagonist (IL-1Ra); however, the attempts thus far have been unsuccessful. The aim of the present study was to investigate whether the lentivirus transduced IL-1Ra gene was able to be stably expressed in murine bone marrow-derived mesenchymal stem cells (mBMSCs) in vitro. In the present study, third generation lentiviral (Lv) vectors transducing the IL 1Ra/green fluorescent protein (copGFP) gene were constructed and transfected into mBMSCs to establish the Lv.IL-1Ra.copGFP/mBMSCs, which were evaluated using fluorescence microscopy, flow cytometry, cell viability analysis using a cell counting kit-8 kit, Trypan blue staining and an MTT growth kinetics assay. The expression of IL-1Ra was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that the Lv.IL-1Ra/copGFP vector was successfully constructed. The mBMSCs exhibited a short proliferation life, however they had good growth kinetics at an early stage and improved viability following efficient transduction of the IL-1Ra gene. IL 1Ra was overexpressed following transfection of mBMSCs. In conclusion, lentiviral vector transduced mBMSCs were able to efficiently express exogenous Il-1Ra under certain conditions and had a marked capacity for proliferation. PMID- 26130371 TI - Hydrogel-derived non-precious electrocatalysts for efficient oxygen reduction. AB - The development of highly active, cheap and robust oxygen reduction reaction (ORR) electrocatalysts to replace precious metal platinum is extremely urgent and challenging for renewable energy devices. Herein we report a novel, green and especially facile hydrogel strategy to construct N and B co-doped nanocarbon embedded with Co-based nanoparticles as an efficient non-precious ORR catalyst. The agarose hydrogel provides a general host matrix to achieve a homogeneous distribution of key precursory components including cobalt (II) acetate and buffer salts, which, upon freeze-drying and carbonization, produces the highly active ORR catalyst. The gel buffer containing Tris base, boric acid and ethylenediaminetetraacetic acid, commonly adopted for pH and ionic strength control, plays distinctively different roles here. These include a green precursor for N- and B-doping, a salt porogen and a Co(2+) chelating agent, all contributing to the excellent ORR activity. This hydrogel-based process is potentially generalizable for many other catalytic materials. PMID- 26130372 TI - Antiviral treatment for Bell's palsy (idiopathic facial paralysis). AB - BACKGROUND: Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. OBJECTIVES: To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. SEARCH METHODS: On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. SELECTION CRITERIA: We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains. DATA COLLECTION AND ANALYSIS: Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. MAIN RESULTS: Eleven trials, including 2883 participants, met the inclusion criteria and are included in the final analysis. We added four studies to the previous review for this update. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found no significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.47 to 1.02, n = 1715). For people with severe Bell's palsy (House-Brackmann scores of 5 and 6 or the equivalent in other scales), we found a reduction in the rate of incomplete recovery at month six when antivirals plus corticosteroids were used (RR 0.64, 95% CI 0.41 to 0.99, n = 478). The outcome for the participants receiving corticosteroids alone was significantly better than for those receiving antivirals alone (RR 2.09, 95% CI 1.36 to 3.20, n = 1169). The treatment effect of placebo was significantly lower than that of antivirals plus corticosteroids (RR 0.56, 95% CI 0.41 to 0.76, n = 658). Antivirals alone had a non-significant detrimental effect on the outcome compared with placebo (RR 1.10, 95% CI 0.87 to 1.40, n = 658). Motor synkinesis or crocodile tearsIn three trials comparing antivirals and corticosteroids with corticosteroids and placebo that assessed this outcome, we found a significant difference in long-term sequelae in favour of antivirals plus corticosteroids (RR 0.73, 95% CI 0.54 to 0.99, n = 869). Three trials comparing antivirals alone with corticosteroids alone investigating this outcome showed fewer sequelae with corticosteroids (RR 1.44, 95% CI 1.11 to 1.85, n = 873). We found no data on long-term sequelae for other comparisons. Adverse events Adverse event data were available in three studies giving comparison data on 1528 participants. None of the four comparisons (antivirals plus corticosteroids versus corticosteroids plus placebo or no treatment; antivirals versus corticosteroids; antivirals plus corticosteroids versus placebo; antivirals versus placebo) showed significant differences in adverse events between treatment and control arms. We could find no correlation with specific treatment within these results. AUTHORS' CONCLUSIONS: Moderate-quality evidence from randomised controlled trials showed no additional benefit from the combination of antivirals with corticosteroids compared to corticosteroids alone for the treatment of Bell's palsy of various degrees of severity. Moderate quality evidence showed a small but just significant benefit of combination therapy compared with corticosteroids alone in severe Bell's palsy. Corticosteroids alone were more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no benefit from antivirals alone over placebo.Moderate-quality evidence indicated that the combination of antivirals and corticosteroids reduced sequelae of Bell's palsy compared with corticosteroids alone.We found no significant increase in adverse events from the use of antivirals compared with either placebo or corticosteroids, based on moderate-quality evidence. PMID- 26130373 TI - The current and future role of endomicroscopy in the management of inflammatory bowel disease. AB - Confocal laser-induced endomicroscopy (CLE), first introduced in 2003, allows the capture of images of "virtual histology" of the gastrointestinal mucosa during endoscopy, providing the opportunity to retrieve real-time visualization of the pathology of the mucosal epithelium with its cellular and subcellular structures. This new endoscopic imaging technique serves as an adjunctive diagnostic tool to the traditional ileocolonoscopy in the management of inflammatory bowel disease (IBD) patients. In multiple clinical trials, CLE has been shown to improve detection of dysplasia, assess disease activity, predict future clinical relapses, and assess potential responsiveness to anti-tumor necrosis factor therapy. This review explores in depth the current and future role of CLE in the management of IBD patients. PMID- 26130374 TI - D-Fagomine attenuates metabolic alterations induced by a high-energy-dense diet in rats. AB - d-Fagomine is a natural iminosugar that counteracts the short-term effects of a high-energy-dense diet on body weight, fasting blood glucose levels and the proportion of gut Enterobacteriales. This suggests that supplementation with d fagomine for longer periods may delay the onset of other factors related to metabolic syndrome. Here we evaluate the effects of d-fagomine dietary supplementation on relevant metabolic hormones and lipid peroxidation. Adult Sprague-Dawley rats were fed a high-fat high-sucrose diet supplemented or not with d-fagomine (0.065% w/w) for 9 weeks. Weight gain, plasma triglycerides, glucose, insulin, glucagon, ghrelin, leptin, and urine F2-isoprostanes were evaluated. d-Fagomine attenuated the changes induced by the high-energy-dense diet in triglycerides and all the hormones tested. These results suggest that d fagomine may help to avert the complications associated with unhealthy eating by counteracting the effects of high-energy-dense diets during the early stages of the development of metabolic disorders. PMID- 26130375 TI - Bone ingrowth around porous-coated acetabular implant: a three-dimensional finite element study using mechanoregulatory algorithm. AB - Fixation of uncemented implant is influenced by peri-prosthetic bone ingrowth, which is dependent on the mechanical environment of the implant-bone structure. The objective of the study is to gain an insight into the tissue differentiation around an acetabular component. A mapping framework has been developed to simulate appropriate mechanical environment in the three-dimensional microscale model, implement the mechanoregulatory tissue differentiation algorithm and subsequently assess spatial distribution of bone ingrowth around an acetabular component, quantitatively. The FE model of implanted pelvis subjected to eight static load cases during a normal walking cycle was first solved. Thereafter, a mapping algorithm has been employed to include the variations in implant-bone relative displacement and host bone material properties from the macroscale FE model of implanted pelvis to the microscale FE model of the beaded implant-bone interface. The evolutionary tissue differentiation was observed in each of the 13 microscale models corresponding to 13 acetabular regions. The total implant-bone relative displacements, averaged over each region of the acetabulum, were found to vary between 10 and 60 MUm. Both the linear elastic and biphasic poroelastic models predicted similar mechanoregulatory peri-prosthetic tissue differentiation. Considerable variations in bone ingrowth (13-88%), interdigitation depth (0.2-0.82 mm) and average tissue Young's modulus (970-3430 MPa) were predicted around the acetabular cup. A progressive increase in the average Young's modulus, interdigitation depth and decrease in average radial strains of newly formed tissue layer were also observed. This scheme can be extended to investigate tissue differentiation for different surface texture designs on the implants. PMID- 26130376 TI - Physico-Chemical and Structural Characteristics of Vegetables Cooked Under Sous Vide, Cook-Vide, and Conventional Boiling. AB - In this paper, physico-chemical and structural properties of cut and cooked purple-flesh potato, green bean pods, and carrots have been studied. Three different cooking methods have been applied: traditional cooking (boiling water at 100 degrees C), cook-vide (at 80 and 90 degrees C) and sous-vide (at 80 degrees C and 90 degrees C). Similar firmness was obtained in potato applying the same cooking time using traditional cooking (100 degrees C), and cook-vide and sous-vide at 90 degrees C, while in green beans and carrots the application of the sous-vide (90 degrees C) required longer cooking times than cook-vide (90 degrees C) and traditional cooking (100 degrees C). Losses in anthocyanins (for purple-flesh potatoes) and ascorbic acid (for green beans) were higher applying traditional cooking. beta-Carotene extraction increased in carrots with traditional cooking and cook-vide (P < 0.05). Cryo-SEM micrographs suggested higher swelling pressure of starch in potatoes cells cooked in contact with water, such as traditional cooking and cook-vide. Traditional cooking was the most aggressive treatment in green beans because the secondary walls were reduced compared with sous-vide and cook-vide. Sous-vide preserved organelles in the carrot cells, which could explain the lower extraction of beta-carotene compared with cook-vide and traditional cooking. Sous-vide cooking of purple-flesh potato is recommended to maintain its high anthocyanin content. Traditional boiling could be recommended for carrots because increase beta-carotenes availability. For green beans, cook-vide, and sous-vide provided products with higher ascorbic acid content. PMID- 26130377 TI - Estimation of bacterial hydrogen sulfide production in vitro. AB - Oral bacterial hydrogen sulfide (H2S) production was estimated comparing two different colorimetric methods in microtiter plate format. High H2S production was seen for Fusobacterium spp., Treponema denticola, and Prevotella tannerae, associated with periodontal disease. The production differed between the methods indicating that H2S production may follow different pathways. PMID- 26130378 TI - Probing the Additional Capacity and Reaction Mechanism of the RuO2 Anode in Lithium Rechargeable Batteries. AB - The structural changes and electrochemical behavior of RuO2 are investigated by using in situ XRD, X-ray absorption spectroscopy, and electrochemical techniques to understand the electrochemical reaction mechanism of this metal oxide anode material. Intermediate phase-assisted transformation of RuO2 to LiRuO2 takes place at the start of discharge. Upon further lithiation, LiRuO2 formed by intercalation decomposes to nanosized Ru metal and Li2 O by a conversion reaction. A reversible capacity in addition to its theoretical capacity is observed on discharging below 0.5 V during which no redox activity involving Ru is observed. TEM, X-ray photoelectron spectroscopy, and the galvanostatic intermittent titration technique are used to probe this additional capacity. The results show that the additional capacity is a result of Li storage in the grain boundary between nanosized Ru metal and Li2 O. Findings of this study provide a better understanding of the quantitative share of capacity by a unique combination of intercalation, conversion, and interfacial Li storage in a RuO2 anode. PMID- 26130379 TI - Timing of diagnosis affects mortality in critical congenital heart disease. AB - OBJECTIVE: Screening for critical congenital heart disease (CHD) with prenatal ultrasound or postnatal pulse oximetry has the potential to improve outcome. To guide screening recommendations, this study aimed to identify the proportion and outcome of major CHD diagnosed before (early) or after (late) postnatal discharge prior to the introduction of postnatal oximetry screening. DESIGN: A retrospective, population-based review of all major CHD in New Zealand from 2006 to 2010. The timing of diagnosis relative to discharge and to intervention in critical and non-critical cases with intention to treat was determined, as was the relationship of diagnostic timing to mortality at 1 year of age. RESULTS: Late diagnosis occurred in 20% of critical and 51% of non-critical cases. Mortality occurred in 18% of critical vs 8% of non-critical cases. Mortality was lower with an early diagnosis of critical CHD (early diagnosis 16% vs late diagnosis 27%, p=0.04). Isolated critical CHD benefited most from early diagnosis (mortality, early diagnosis 12% vs late diagnosis 29%, p=0.002). Early diagnosis occurred in >90% critical complex CHD and hypoplastic left heart syndrome, 85% d transposition of the great arteries (d-TGA) and 53% critical left ventricular outflow tract obstruction (LVOTO). Deaths in d-TGA and LVOTO primarily occurred prior to intervention and for d-TGA most often when birth was distant from the cardiac centre. CONCLUSIONS: Excess mortality occurs following late diagnosis of critical CHD, and for d-TGA even with early diagnosis if intervention is not immediately available. Antenatal detection retains an important role in reducing mortality related to critical CHD. PMID- 26130381 TI - Question 1: Role of methotrexate in severe atopic eczema in children. PMID- 26130382 TI - Severe combined immunodeficiency syndrome presenting with disseminated BCG infection. PMID- 26130383 TI - Nutritional status and nutritional management in children with cancer. AB - Malnutrition is often seen at the point of diagnosis in childhood malignancy or may develop during the course of treatment. Strategies for optimal diagnosis and management of nutritional problems in children with cancer are limited in the published literature. Identification of children who may be malnourished or at nutritional risk can be achieved through improved approaches for risk stratification and classification. Once recognised, various strategies have been demonstrated to reduce malnutrition, minimise side effects of treatment and improve survival. Novel approaches in vivo and adult oncology populations provide future avenues for investigation. PMID- 26130380 TI - Varicella paediatric hospitalisations in Belgium: a 1-year national survey. AB - BACKGROUND: Varicella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1 year period. METHODS: Data on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash. RESULTS: Participation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/10(5) person-years, with the highest impact among those 0-4 years old (global incidence and odds of hospitalisation: 79/10(5) person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had >=1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/10(5) person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/10(6) and fatality ratio 0.2% among our cohort. CONCLUSIONS: Varicella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium. PMID- 26130384 TI - Abusive head trauma and accidental head injury: a 20-year comparative study of referrals to a hospital child protection team. AB - AIM: To describe children referred for suspected abusive head trauma (AHT) to a hospital child protection team in Auckland, New Zealand. METHODS: Comparative review of demographics, histories, injuries, investigations and diagnostic outcomes for referrals under 15 years old from 1991 to 2010. RESULTS: Records were available for 345 children. Referrals increased markedly (88 in the first decade, 257 in the second), but the diagnostic ratio was stable: AHT 60%, accidental or natural 29% and uncertain cause 11%. The probability of AHT was similar regardless of socio-economic status or ethnicity. In children under 2 years old with accidental head injuries (75/255, 29%) or AHT (180/255, 71%), characteristics of particular interest for AHT included no history of trauma (88/98, 90%), no evidence of impact to the head (84/93, 90%), complex skull fractures with intracranial injury (22/28, 79%), subdural haemorrhage (160/179, 89%) and hypoxic ischaemic injury (38/39, 97%). In children over 2 years old, these characteristics did not differ significantly between children with accidental head injuries (21/47, 45%) and AHT (26/47, 55%). The mortality of AHT was higher in children over 2 years old (10/26, 38%) than under 2 years (19/180, 11%). CONCLUSIONS: The striking increase in referrals for AHT probably represents increasing incidence. The decision to refer a hospitalised child with a head injury for assessment for possible AHT should not be influenced by socio-economic status or ethnicity. Children over 2 years old hospitalised for AHT are usually injured by mechanisms involving impact and should be considered at high risk of death. PMID- 26130385 TI - Laser Atherectomy for Treatment of Femoropopliteal In-Stent Restenosis. AB - PURPOSE: To investigate if laser atherectomy with adjunctive balloon angioplasty can improve endovascular treatment outcomes for femoropopliteal in-stent restenosis (ISR). METHODS: A dual center study included 135 symptomatic patients (mean age 71 years; 76 men) who underwent endovascular treatment of femoropopliteal ISR between 2006 and 2013. Of these, 54 (40%) were treated with laser atherectomy and the remaining 81 patients with balloon angioplasty alone. Angiographic images were reviewed for lesion morphology and characteristics, TransAtlantic InterSociety Consensus (TASC) II classification, and distal runoff. Class I ISR was defined as focal lesions <=50 mm, class II ISR as lesions >50 mm, and class III ISR as stent total occlusion. Recurrent ISR was determined by a peak systolic velocity ratio >2.4 by duplex ultrasound. RESULTS: Patients treated with laser atherectomy had longer mean ISR lesion length (222 vs 114 mm, p<0.001) and more class III ISR (69% vs 20%, p=0.001). There was no association between laser atherectomy and rates of recurrent restenosis or occlusion for patients with class I/II ISR, but there was a significantly lower rate of target lesion revascularization at 2 years among patients treated with laser atherectomy (14% vs 44%, p=0.05). In comparison, patients with class III ISR treated with laser atherectomy had lower rates of recurrent restenosis at 1 year (54% vs 91%, p=0.05) and 2 years (69% vs 100%, p=0.05). Patients with class III ISR treated with laser atherectomy also had lower rates of recurrent in-stent occlusion at 2 year follow-up (33% vs 71%, p=0.04). CONCLUSION: When used to treat complex ISR, including in-stent occlusions, laser atherectomy with adjunctive balloon angioplasty may be associated with improved patency. PMID- 26130386 TI - Anaphylactic Reaction During Implantation of the Ovation Stent-Graft System in a Patient With Abdominal Aortic Aneurysm. AB - PURPOSE: To describe a case of anaphylactic reaction during implantation of the Ovation Abdominal Stent Graft System in a patient treated for abdominal aortic aneurysm (AAA). CASE REPORT: An 82-year-old man with a 5.3-cm asymptomatic AAA underwent endovascular repair using an Ovation stent-graft. Polymer was infused into the inflatable rings of the aortic body under continuous angioscopy, but the rings were not filled, even though the entire amount of the polymer was administered. Simultaneously, the patient presented with a severe anaphylactic reaction resulting in cardiopulmonary arrest. He was successfully resuscitated, but the procedure was abandoned; the patient refused any further treatment. CONCLUSION: A rupture of the Ovation main body's polymer-filled rings may lead to extremely severe anaphylactic reaction. PMID- 26130387 TI - The effect of progressive muscle relaxation on daily cortisol secretion. AB - Abbreviated progressive muscle relaxation (APMR) is a much used stress-management technique. Its efficacy relevant to placebo control is already established in the literature and the primary aim of the present study was to ascertain whether its proven impact on psychological stress measures is matched by a decrease in prevailing levels of the stress-associated hormone cortisol, using accurate and robust measurement based on multiple sampling of full diurnal cortisol secretion profiles. First-year university students can face significant stress in adjustment to academic demands and immersion in a novel social network and provided a convenient study population. One hundred and one first-year students completed APMR with prevailing stress levels assessed a week before and after intervention. Both cortisol and self-report measures were significantly reduced post-intervention by 8% and 10%, respectively. The efficacy of the intervention was independent of, and not modulated by neuroticism, gender, age and smoking status. We also demonstrated that cortisol reduction was unlikely to have been a consequence of adaptation to any initial cortisol elevation prompted by the challenge of the demanding saliva collection protocol. We conclude that the efficacy of APMR in this population extends to reduction in biologically expressed stress levels as well as levels based solely on self-report. PMID- 26130388 TI - Molecular evolution of haemagglutinin (H) gene in measles virus. AB - We studied the molecular evolution of the haemagglutinin (H) gene (full length) in all genotypes (24 genotypes, 297 strains) of measles virus (MeV). The gene's evolutionary timescale was estimated by the Bayesian Markov chain Monte Carlo (MCMC) method. We also analysed positive selection sites. The MCMC tree indicated that the MeV H gene diverged from the rinderpest virus (same genus) about 250 years ago and that 24 MeV genotypes formed 3 lineages dating back to a 1915 ancestor (95% highest posterior density [HPD] 1882-1941) with relatively rapid evolution (mean rate: 9.02 * 10(-4) substitutions/site/year). The 3 lineages diverged in 1915 (lineage 1, 95% HPD 1882-1941), 1954 (lineage 2, 95% HPD 1937 1969), and 1940 (lineage 3, 95% HPD 1927-1952). These 24 genotypes may have diverged and emerged between the 1940s and 1990 s. Selective pressure analysis identified many negative selection sites on the H protein but only a few positive selection sites, suggesting strongly operated structural and/or functional constraint of changes on the H protein. Based on the molecular evolution of H gene, an ancestor MeV of the 24 genotypes emerged about 100 years ago and the structure of H protein has been well conserved. PMID- 26130390 TI - Asymmetric Pulses in a 5-Year-Old Asian Female: Is It Worth Further Investigations? PMID- 26130391 TI - Prolonged Activity Restriction After Concussion: Are We Worsening Outcomes? AB - The current treatment of concussion or mild traumatic brain injury (mTBI) is primarily based on expert consensus. Most clinical practice guidelines advise cognitive and physical rest after injury including withdrawal from normal life activities such as school attendance, sports participation, and technology use until symptoms resolve. Some individuals who sustain an mTBI experience persistent physical, cognitive, and mental health problems. Activity restriction itself may contribute to protracted recovery and other complications. Williamson's Activity Restriction Model of Depression, formulated more than 20 years ago, is central to this hypothesis. We review research evidence for potential harms of prolonged activity restriction and report an mTBI case as an example of how an "activity restriction cascade" can unfold. According to this model, psychological consequences of removal from validating life activities, combined with physical deconditioning, contribute to the development and persistence of postconcussive symptoms after mTBI in some youth. A modification to mTBI guidelines that emphasizes prompt reengagement in life activities as tolerated is encouraged. PMID- 26130389 TI - Modeling cancer metabolism on a genome scale. AB - Cancer cells have fundamentally altered cellular metabolism that is associated with their tumorigenicity and malignancy. In addition to the widely studied Warburg effect, several new key metabolic alterations in cancer have been established over the last decade, leading to the recognition that altered tumor metabolism is one of the hallmarks of cancer. Deciphering the full scope and functional implications of the dysregulated metabolism in cancer requires both the advancement of a variety of omics measurements and the advancement of computational approaches for the analysis and contextualization of the accumulated data. Encouragingly, while the metabolic network is highly interconnected and complex, it is at the same time probably the best characterized cellular network. Following, this review discusses the challenges that genome-scale modeling of cancer metabolism has been facing. We survey several recent studies demonstrating the first strides that have been done, testifying to the value of this approach in portraying a network-level view of the cancer metabolism and in identifying novel drug targets and biomarkers. Finally, we outline a few new steps that may further advance this field. PMID- 26130392 TI - Identifying Social Determinants of Health and Legal Needs for Children With Special Health Care Needs. AB - Children with special health care needs (CSHCN) require comprehensive care with high levels of community and government assistance. Medical-legal partnerships may be particularly suited to address needs for this population. To explore this, we conducted in-depth telephone interviews of families of CSHCN cared for in the primary care practice of our tertiary care children's hospital. The majority of the sample (N = 46) had been late on housing payments and 17% of homeowners had been threatened with foreclosure. Families frequently reported denial of public benefits. Approximately 10% had executed advance planning documents such as guardianship plans for the children or wills for the parents. A minority of families had sought help from community agencies or lawyers. Less than one third had ever discussed any of the issues with health care providers, but two thirds were likely or very likely to in the future. CSHCN may especially benefit from the social support of a medical-legal partnership. PMID- 26130393 TI - Using Clinical Data to Predict Accurate ADHD Diagnoses Among Urban Children. AB - Diagnosing attention deficit hyperactivity disorder (ADHD) requires reports of child behavior from 2 settings-most commonly home and school. Obtaining this information from teachers, however, is often challenging. We sought to determine if clinical data, supplementary to parent symptom scales, could be useful in predicting DSM-compliant diagnoses. Parents and teachers reported ADHD symptoms for 156 children using Vanderbilt scales; care managers collected clinical data; a team of specialists determined whether children met diagnostic criteria for ADHD. The ability of a parent Vanderbilt alone to predict an ADHD diagnosis was 56% (95% confidence interval = 45%, 67%). By adding child age and grade retention history to the multivariable model, the probability rose to 78% (95% confidence interval = 59%, 93%). In the maximally predictive model-which included 5 covariates-the predictive validity rose to 84% (95% confidence interval = 52%, 99%). Supplementing parent symptom reports with clinical data may be a viable alternative in certain cases when teacher reports are unavailable. PMID- 26130394 TI - Heads Up: Communication Is Key in School Nurses' Preparedness for Facilitating "Return to Learn" Following Concussion. AB - BACKGROUND: Recent literature advocates for a school academic team, including school nurses, to support concussed students' return to the classroom. This study aimed to assess the current understanding and practices of a sample of school nurses regarding the concept of "return to learn" in concussed students. METHODS: Cross-sectional survey of New England school nurses. RESULTS: The greatest barrier to the school nurses' functioning within the academic rehabilitation team for students with concussion was "inadequate communication with the provider that diagnosed the concussion" (73%). Of the 151 school nurses surveyed, 19% felt that they did not have the training necessary for this role. Other barriers included "inadequate concussion training" (38%) and "inadequate time necessary to care for a student with concussion" (30%). CONCLUSIONS: By identifying specific gaps in knowledge and challenges at the school level, these results inform interdisciplinary medical teams about the importance of educating and facilitating effective "return to learn" academic plans. PMID- 26130395 TI - Pediatric Sunscreen and Sun Safety Guidelines. PMID- 26130396 TI - Prevalence of Autism Spectrum Disorder in Children Referred for Diagnostic Autism Evaluation. AB - Increased public awareness of autism spectrum disorders (ASD) and routine screening in primary care have contributed to increased requests for diagnostic ASD evaluations. However, given the scarcity of subspecialty autism diagnostic resources, overreferral of children suspected of having ASD may be contributing to long waiting lists at tertiary care autism centers and delaying diagnosis for those children who truly have ASD. To determine whether children are being excessively referred to ASD-specific diagnostic clinics, our objective was to determine the prevalence of true ASD diagnoses in children referred for diagnostic ASD evaluation. Charts of all patients referred to a regional autism center between April 2011 and August 2012 for suspicion of a possible ASD were retrospectively reviewed and demographic and clinical diagnoses abstracted. Only 214 of 348 patients evaluated (61%) received an ASD diagnosis. Thus, concerns about autism are not confirmed by an ASD diagnosis in a significant number of children. PMID- 26130397 TI - The Study of Effect for General Movements Assessment in the Diagnosis of Neurological Development Disorders: A Meta-Analysis. AB - OBJECTIVE: To discuss the value of general movements assessment in predicting the neurological disorders. METHODS: Using PubMed as the search engine, we searched to identify relevant studies in English and Chinese language published up to November 2014 and 19 studies were selected. Standard methods in meta-analyses were used to provide diagnostic accuracy by Meta-DiSc 1.4. RESULTS: For non cerebral palsy (non-CP) as outcome for writhing period, the results suggested a good sensitivity and a specificity of 0.74, the Q-value was 0.80. The area under the curve (AUC) was 0.87. For non-CP as outcome for fidgety period, the results suggested both high level for sensitivity and specificity. And the Q-value was 0.914, the AUC was 0.9664. For CP as outcome for writhing and fidgety periods, good sensitivity and specificity were found in the analysis, and the Q-value was 0.9034 while the AUC was 0.9592. CONCLUSION: General movements assessment is a good predictor for diagnosing neurological disorders. PMID- 26130398 TI - The Prevalence of Food Allergies in Children Referred to a Multidisciplinary Feeding Program. AB - OBJECTIVE: To assess the prevalence of food allergy in children presenting to a multidisciplinary feeding program. METHODS: A retrospective chart review was conducted from 302 patients. We recorded history of food reaction, family history of any atopic disease, radioallergosorbent testing, prematurity, birth weight, breastfeeding history, Z-scores, age, and gastrointestinal mucosal biopsy reports with eosinophilic infiltrate. Three categories of possible food allergy were stratified based on increasing evidence of allergy. RESULTS: Possible food allergy was found for 18% (n = 54), likely food allergy for 6% (n = 18), and very likely food allergy for 16% (n = 47) for a total of 40% classified in a food allergy group. Having been breastfed correlated with likelihood of food allergy but tube-feeding dependence did not. CONCLUSION: This study revealed a higher proportion of children in a feeding program with food allergy compared to the general population, but larger prospective studies are needed to confirm the association. PMID- 26130399 TI - Amino Azaxylylenes Photogenerated from o-Amido Imines: Photoassisted Access to Complex Spiro-Poly-Heterocycles. AB - Upon irradiation, cyclic imines containing o-amido groups are shown to produce reactive intermediates, amino azaxylylenes, which undergo intramolecular cycloadditions to tethered unsaturated pendants to yield complex N,O-heterocycles having an additional spiro-connected nitrogen heterocyclic moiety. Modular assembly of the photoprecursors allows expeditious increase of the complexity of the target poly-heterocyclic scaffolds with a minimal number of experimentally simple reaction steps. The photocyclization and subsequent postphotochemical transformations are accompanied by an increase of Lovering's fsp3 factor, thus producing unprecedented three-dimensional molecular architectures, and offering extended sampling of chemical space. PMID- 26130400 TI - Chin Microgenia: A Clinical Comparative Study. AB - BACKGROUND: The aesthetic relevance of the chin and its relatively simple correction through different approaches make genioplasty one of the most performed aesthetic procedures of the face. Sliding genioplasty is extremely rewarding, particularly when performed as an adjunction to rhinoplasty, rhytidectomy, or jaw surgery. In the scientific literature, many different surgical techniques are described, but the biological implications and the economical impact can shape the surgeon's decision on which can be the best treatment: surgical correction with osteotomy, chin implants, or with fillers. OBJECTIVE: The authors propose a decision making protocol for correcting chin microgenia based on a revision of 345 treated cases. METHODS: A retrospective review of 345 cases of chin microgenia was undertaken to understand the proper preoperative assessment and therapeutic planning. A total of 135 patients were treated with surgical sliding genioplasty (group A): 60 patients (group B) have been grafted with alloplastic implants and the remaining 150 patients (group C) with hyaluronic acid. We recorded clinical indications, complications, and long term aesthetic results at 3-year follow-up. RESULTS: The analysis of the results based on the entity of the chin's sagittal defect, the chin soft-tissue thickness, the patient's age, and self-judgment allows for simplified treatment planning for sagittal chin deformities showing a greater predictability and a more stable long-term aesthetic result regarding sliding genioplasty compared to alloplastic implant placement and fillers. CONCLUSIONS: Our proposal for a simple and versatile protocol of chin microgenia aims to simplify the therapeutic indications for a predictable and a stable long-term aesthetic result. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 26130401 TI - High-frame rate four dimensional optoacoustic tomography enables visualization of cardiovascular dynamics and mouse heart perfusion. AB - Functional imaging of mouse models of cardiac health and disease provides a major contribution to our fundamental understanding of the mammalian heart. However, imaging murine hearts presents significant challenges due to their small size and rapid heart rate. Here we demonstrate the feasibility of high-frame-rate, noninvasive optoacoustic imaging of the murine heart. The temporal resolution of 50 three-dimensional frames per second provides functional information at important phases of the cardiac cycle without the use of gating or other motion reduction methods. Differentiation of the blood oxygenation state in the heart chambers was enabled by exploiting the wavelength dependence of optoacoustic signals. Real-time volumetric tracking of blood perfusion in the cardiac chambers was also evaluated using indocyanine green. Taken together, the newly-discovered capacities offer a unique tool set for in-vivo structural and functional imaging of the whole heart with high spatio-temporal resolution in all three dimensions. PMID- 26130402 TI - Leishmania cell wall as a potent target for antiparasitic drugs. A focus on the glycoconjugates. AB - Although leishmaniasis has been studied for over a century, the fight against cutaneous, mucocutaneous and visceral forms of the disease remains a hot topic. This review refers to the parasitic cell wall and more particularly to the constitutive glycoconjugates. The structures of the main glycolipids and glycoproteins, which are species-dependent, are described. The focus is on the disturbance of the lipid membrane by existing drugs and possible new ones, in order to develop future therapeutic agents. PMID- 26130404 TI - Modification mechanism of praseodymium doping for the photocatalytic performance of TiO2: a combined experimental and theoretical study. AB - Impurity doping is a simple and efficient modification method to improve the photocatalytic performance of wide band gap photocatalysts. However, some basic and important issues about the mechanism of impurity doping modification still need to be further confirmed and explained. In the present work, Pr-doped TiO2 with a mono-phase crystal structure was prepared by a sol-gel method. Then, the crystal structure, binding information, optical absorption, and photocatalytic activity were systematically investigated. The experimental results show that Pr doping could significantly enhance the photocatalytic activity of TiO2, and the effects of modification on rutile TiO2 are more obvious than for anatase TiO2. In order to understand the underlying mechanism, density functional theory was utilized to calculate the crystal structure and electronic structure of pure and Pr-doped TiO2. The differences in electronic structure between anatase and rutile phases lead to the above photocatalytic performance. The experimental measurements and theoretical calculations mutually support each other in the present work. Two points are confirmed: the position of the band edge determines the redox activity of the photocatalyst, and the shallow energy bands induced by impurity doping could improve the photocatalytic performance. PMID- 26130403 TI - Comparison of intrinsic dynamics of cytochrome p450 proteins using normal mode analysis. AB - Cytochrome P450 enzymes are hemeproteins that catalyze the monooxygenation of a wide-range of structurally diverse substrates of endogenous and exogenous origin. These heme monooxygenases receive electrons from NADH/NADPH via electron transfer proteins. The cytochrome P450 enzymes, which constitute a diverse superfamily of more than 8,700 proteins, share a common tertiary fold but < 25% sequence identity. Based on their electron transfer protein partner, cytochrome P450 proteins are classified into six broad classes. Traditional methods of pro are based on the canonical paradigm that attributes proteins' function to their three dimensional structure, which is determined by their primary structure that is the amino acid sequence. It is increasingly recognized that protein dynamics play an important role in molecular recognition and catalytic activity. As the mobility of a protein is an intrinsic property that is encrypted in its primary structure, we examined if different classes of cytochrome P450 enzymes display any unique patterns of intrinsic mobility. Normal mode analysis was performed to characterize the intrinsic dynamics of five classes of cytochrome P450 proteins. The present study revealed that cytochrome P450 enzymes share a strong dynamic similarity (root mean squared inner product > 55% and Bhattacharyya coefficient > 80%), despite the low sequence identity (< 25%) and sequence similarity (< 50%) across the cytochrome P450 superfamily. Noticeable differences in Calpha atom fluctuations of structural elements responsible for substrate binding were noticed. These differences in residue fluctuations might be crucial for substrate selectivity in these enzymes. PMID- 26130406 TI - The Role of Osmotic Therapy in Hemispheric Stroke. AB - BACKGROUND: Decompressive hemicraniectomy (DHC) can be lifesaving in hemispheric stroke complicated by cerebral edema. Conversely, osmotic agents have not been shown to improve survival, despite their widespread use. It is unknown whether medical measures can similarly confer survival in certain patient subgroups. We hypothesized that osmotic therapy (OT) without DHC may be associated with a greater likelihood of survival in particular populations depending on demographic, radiologic, or treatment characteristics. METHODS: We performed a retrospective cohort analysis of patients with large anterior circulation strokes with an NIH stroke scale (NIHSS) >=10 who received OT. We compared clinical, radiologic, and treatment characteristics between two groups: (1) those who survived until discharge with only OT (medical management success) and (2) those who required either DHC or died (medical management failure). RESULTS: Thirty patients met eligibility criteria. Median NIHSS was 19 [interquartile range (IQR) 13-24], and median GCS was 10 [IQR 8-14]. Forty-seven percent of the medical management cohort survived to discharge. Demographic characteristics associated with medical management success included NIHSS (p = 0.009) and non-black race (p = 0.003). Of the various interventions, the administration of OT after 24 hours and a smaller hypertonic saline dose was also associated with survival to discharge (p = 0.038 and 0.031 respectively). CONCLUSION: Our results suggest that patients with moderate size hemispheric infarcts on presentation and those who do not require OT within the first 24 h of stroke may survive until discharge with medical management alone. Black race was also associated with conservative management failure, a finding that may reflect a cultural preference toward aggressive management. Further prospective studies are needed to better establish the utility of medical management of hemispheric edema in the setting of moderate size hemispheric infarcts. PMID- 26130405 TI - Early Quantitative Gamma-Band EEG Marker is Associated with Outcomes After Cardiac Arrest and Targeted Temperature Management. AB - BACKGROUND: Brain recovery after cardiac arrest (CA) is sensitive to temperature. Yet the effect of temperature management on different EEG frequency bands has not been elucidated. A novel quantitative EEG algorithm, sub-band information quantity (SIQ), was applied to evaluate EEG recovery and outcomes after CA. METHODS: Twenty-four Wistar rats undergoing 7-min CA were randomly assigned to immediate hypothermia (32-34 degrees C), normothermia (36.5-37.5 degrees C), or hyperthermia (38.5-39.5 degrees C) (n = 8). EEG was recorded continuously for the first 8 h and then for serial 30-min epochs daily. The neurologic deficit score (NDS) at 72-h was the primary functional outcome. Another four rats without brain injury were added as a control. RESULTS: Better recovery of gamma-band SIQ was found in the hypothermia group (0.60 +/- 0.03) compared with the normothermia group (0.40 +/- 0.03) (p < 0.01) and in the normothermia group compared with the hyperthermia group (0.34 +/- 0.03) (p < 0.05). The NDS was also improved in the lower temperature groups: hypothermia [median (25th, 75th), 74 (61, 74)] versus normothermia [49 (47, 61)] versus hyperthermia [43 (0, 50)] (p < 0.01). Throughout the 72-h experiment, the gamma-band SIQ showed the strongest correlation at every time point (ranging 0.520-0.788 from 30-min to 72-h post resuscitation, all p < 0.05) whereas the delta-band SIQ had poor correlation with the 72-h NDS. No significant difference of sub-band EEG was found with temperature manipulation alone. CONCLUSIONS: Recovery of gamma-band SIQ-qEEG was strongly associated with functional outcomes after CA. Induced hypothermia was associated with faster recovery of gamma-band SIQ and improved functional outcomes. Targeted temperature management primarily affected gamma frequency oscillations but not delta rhythm. PMID- 26130407 TI - CARD14 Glu138 mutation in familial pityriasis rubra pilaris does not warrant differentiation from familial psoriasis. AB - Some familial cases of pityriasis rubra pilaris (PRP) have the CARD14 gene mutations that are also detected in familial psoriasis vulgaris. However, genotype-phenotype correlation in these two entities is poorly understood. Here, we report a case of PRP with a new mutation in CARD14. Genomic analysis of a 40 year-old female patient with sporadic PRP type V identified a heterozygous dominant c.412G>A mutation (p.Glu138Lys) in CARD14. Two types of CARD14 mutations causing Glu138 substitutions have been reported in cases of familial PRP and pustular psoriasis. All three types, including the present case, are predicted to cause similar loss of the negative charges at this site. This suggests that the difference in molecular charge and the resulting change in molecular interaction around the N-terminal end of the coiled-coil region of CARD14 molecule do not determine the phenotypic differences between psoriasis and PRP. PMID- 26130408 TI - Discovery of 2-arylamino-4-(1-methyl-3-isopropylsulfonyl-4-pyrazol amino)pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors. AB - A new series of 2,4-diamino pyrimidine derivatives with a sulfone-substituted pyrazole right side-chain were discovered as potent anaplastic lymphoma kinase inhibitors. Structure-activity relationship of the left side-chain on phenyl substitutions were explored which delivered many potent ALK inhibitors. Among them, 29a showed favorable pharmacokinetic profiles in rats and dogs together with significant antitumor efficacy in EML4-ALK fusion xenograft model. PMID- 26130409 TI - Cell-free expression with the toxic amino acid canavanine. AB - Canavanine is a naturally occurring noncanonical amino acid, which is analogous to arginine. It is a potent antimetabolite and natural allelochemic agent, capable of affecting or blocking regulatory and catalytic reactions that involve arginine. Incorporated into proteins at arginine positions, canavanine can be detrimental to protein stability and functional integrity. Although incorporation of canavanine into proteins has long been documented, due to its toxicity, expression in Escherichia coli and other common hosts remains a considerable challenge. Here, we present a simple, cell-free expression system with markedly improved performance compared to heterologous expression. The cell-free expression system does not require any tuning besides substitution of arginine by canavanine. We show that our technique enables highly efficient protein expression in small volumes with arginine being fully replaced by canavanine for functional and structural studies. PMID- 26130411 TI - Degradation of chlorpyrifos residues in apple under temperate conditions of Kashmir Valley. AB - The present studies were carried out to observe the dissipation pattern of chlorpyrifos on apple in Kashmir Valley. Persistence of chlorpyrifos in apple was studied following two applications rates of chlorpyrifos (Dursban 20 EC) at 200 g a.i. ha(-1) (single dose T 1) and 400 g a.i. ha(-1) (double dose T 2). The average initial deposit of chlorpyrifos was found to be 1.61 and 1.98 MUg g(-1) for T 1 and T 2 application rates respectively on apple. The residues dissipated to 0.09 and 0.06 MUg g(-1) after 15- and 30-day post treatment with half-life periods of 3.34 and 5.47 days in T 1 and T 2 application rates, respectively. The residues of chlorpyrifos dissipated to below limit of quantification (LOQ) of 0.04 MUg g(-1) after 30 day at T 1 application rate. A waiting period of 6 days must be observed for chlorpyrifos on apple at recommended application rate for the safety of consumers. Theoretical maximum residue contribution (TMRC) values were found to be far less than maximum permissible intake (MPI) at 0 day in both the dosages suggesting chlorpyrifos on apple in Kashmir is unlikely to cause health risks. PMID- 26130412 TI - Addiction to transmucosal fentanyl: Is it a cause for concern in cancer pain management? PMID- 26130410 TI - Exosomes Derived from Breast Cancer Cells, Small Trojan Horses? AB - Exosomes are small extracellular vesicles secreted to the extracellular environment by several cell types, including tumor cells. It has been demonstrated that exosomes have an important role in intercellular communication, but they have recently been implicated in various tumor processes, including the oncogenic transformation of cells in the tumor microenvironment, tumor drug resistance, and the transport of tumor factors. Tumors appear to use exosomes to dialogue with and transform neighboring cells to create an ideal environment for their growth and expansion. On the other hand, the structure and function of exosomes may make them useful in cancer diagnosis and prognosis, because they contain molecules that could serve as biomarkers, including oncogenes, miRNAs, and certain proteins. They have the ability to travel via body fluids, from which they could be isolated and used to transport drugs to specific targets. This review aims to provide an update on the role of exosomes derived from breast cancer cells. PMID- 26130413 TI - Promoter hypermethylation of the cysteine protease RECK may cause metastasis of osteosarcoma. AB - The present study examined the role of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) promoter hypermethylation as a causative factor in metastasis of osteosarcoma. Using human pathological samples, it is demonstrated that RECK, a cysteine protease that reversibly regulates expression of matrix metalloproteases like matrix metallopeptidase 9 (MMP9), is transcriptionally inhibited in osteosarcoma, especially metastatic variants. This result comes from its promoter hypermethylation, as evaluated in the present study by methylation specific PCR reaction. The expression of RECK was also significantly diminished in the metastatic variants of osteosarcoma. This downregulation of RECK in advanced grades of osteosarcoma and metastatic grades was also associated with the increased expression of invadosome-specific markers like MMP9, phospho-FAK, and integrins, suggesting the complex contributions of RECK in the prevention of metastasis and its downregulation as a causative factor in osteosarcoma metastasis. PMID- 26130414 TI - Carbonic anhydrase IX overexpression regulates the migration and progression in oral squamous cell carcinoma. AB - Carbonic anhydrase IX (CAIX) is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study investigated the association between membrane expression of CAIX and the clinicopathological characteristics in oral squamous cell carcinoma (OSCC) patients. The study used immunohistochemistry to examine CAIX expression in 271 OSCC specimens by tissue microarray (TMA) and assessed the effect of CAIX overexpression and knockdown on migration of oral cancer cells in vitro. We found that CAIX expression was associated with more advanced clinical stages (p = 0.030) and positive lymph node metastasis (p = 0.026). Importantly, CAIX expression was correlated with a poorer patient prognosis in a univariate survival analysis (p = 0.025). Moreover, CAIX suppression by small interfering RNA (siRNA) significantly reduced cellular migration in OECM-1 oral cancer cell. In conclusion, our study showed that the expression of CAIX in OSCC samples can predict the progression of OSCC and survival of OSCC patients in Taiwan. PMID- 26130415 TI - Effect of ERCC8 tagSNPs and their association with H. pylori infection, smoking, and alcohol consumption on gastric cancer and atrophic gastritis risk. AB - Excision repair cross-complementing group 8 (ERCC8) plays a critical role in DNA repair. Genetic polymorphisms in ERCC8 may contribute to the risk of cancer development. We selected tag single nucleotide polymorphisms (tagSNPs) in Chinese patients from the HapMap database to investigate associations with gastric cancer and its precursors. Genomic DNA was extracted from 394 controls, 394 atrophic gastritis, and 394 gastric cancer cases in northern Chinese patients, and genotypes were identified using the Sequenom MassARRAY system. We found that the ERCC8 rs158572 GG+GA genotype showed a 1.651-fold (95 % confidence interval (CI) = 1.109-2.457, P = 0.013) increased risk of gastric cancer compared with the AA genotype, especially in diffuse type. Stratified analysis comparing the common genotype revealed significantly increased gastric cancer risk in males and individuals older than 50 years with rs158572 GA/GG/GG+GA genotypes, while individuals older than 50 years with rs158916 CT/CC+CT genotypes were less susceptible to atrophic gastritis. Haplotype analysis showed that the G-T haplotype was associated with increased risk of gastric cancer. Statistically significant interactions between the two ERCC8 tagSNPs and Helicobacter pylori infection were observed for gastric cancer and atrophic gastritis risk (P < 0.05). Smokers and drinkers with ERCC8 rs158572 GG+GA genotype were more susceptible to gastric cancer compared with non-smokers and non-drinkers homozygous for AA. Our findings suggested that ERCC8 rs158572 and rs158916, alone or together with environmental factors, might be associated with gastric cancer and atrophic gastritis susceptibility. Further validation of our results in larger populations along with additional studies evaluating the underlying molecular function is required. PMID- 26130417 TI - Pharmacoscintigraphy studies to assess the feasibility of a controlled release formulation of ziprasidone. AB - Ziprasidone, like many BCS Class II drugs with low intrinsic solubility and a strong tendency to crystallize from supersaturated solutions, presents significant technical challenges when developing an oral controlled release dosage form. In order to achieve acceptable bioavailability and prolonged exposures for once-daily dosing, good colonic absorption and a reliable controlled release (CR) technology are necessary. To this end, a novel solubilized drug form--coated crystals made by spray drying (CCSD), was formulated and progressed into human clinical studies. This report describes studies of colonic absorption for the CCSD using the EnterionTM capsule and a pharmacoscintigraphy study in which the CCSD was orally administered via a radiolabelled osmotic tablet formulation. These studies demonstrated that the probability of achieving the required drug solubilization in the colon with the CCSD concept and thereby the desired once daily pharmacokinetic profile was extremely low. PMID- 26130416 TI - Chemokines and their receptors in esophageal cancer--the systematic review and future perspectives. AB - Esophageal cancer (EC) is an aggressive malignant solid tumor with rapid progression and unfavorable prognosis. The 5-year survival rate for EC patients was estimated to be less than 10 %. Therefore, there is an urgent need to improve diagnostic tool and effective treatment therapies for EC patients. In our paper, the general structure and function of chemokines and their receptors as well as their role in cancer progression were shortly presented. Moreover, the aim of our paper was to summarize and refer the current findings concerning the role of selected chemokines and their receptors as candidates for tumor markers of EC. Some clinical investigations have proved the involvement of these proteins in proliferation, migration, invasiveness and metastasis of tumor cells. Increasing evidence from previous studies suggested that C-X-C motif chemokine 12 (CXCL12), also known as stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 may provide novel diagnostic and prognostic strategies to reduce the burden of EC. Moreover, therapy targeting the CXCL12/CXCR4 axis may open a new direction for treatment of EC patients. However, given their nonspecific nature, the diagnostic value of chemokines and their receptors may be limited. Therefore, future larger investigations, especially in the blood of EC patients, still need to be continued to further clarify the significance of these proteins as potential candidates for tumor markers in diagnosis and prognosis of EC patients. PMID- 26130418 TI - Influencing the properties of dysprosium single-molecule magnets with phosphorus donor ligands. AB - Single-molecule magnets are a type of coordination compound that can retain magnetic information at low temperatures. Single-molecule magnets based on lanthanides have accounted for many important advances, including systems with very large energy barriers to reversal of the magnetization, and a di-terbium complex that displays magnetic hysteresis up to 14 K and shows strong coercivity. Ligand design is crucial for the development of new single-molecule magnets: organometallic chemistry presents possibilities for using unconventional ligands, particularly those with soft donor groups. Here we report dysprosium single molecule magnets with neutral and anionic phosphorus donor ligands, and show that their properties change dramatically when varying the ligand from phosphine to phosphide to phosphinidene. A phosphide-ligated, trimetallic dysprosium single molecule magnet relaxes via the second-excited Kramers' doublet, and, when doped into a diamagnetic matrix at the single-ion level, produces a large energy barrier of 256 cm(-1) and magnetic hysteresis up to 4.4 K. PMID- 26130419 TI - Association study of C936T polymorphism of the VEGF gene and the C242T polymorphism of the p22phox gene with diabetes mellitus type 2 and distal diabetic polyneuropathy. AB - Even with long-term glycemic control, diabetes mellitus type 2 (DM2) remains the predominant cause of diabetic neuropathy. Single nucleotide polymorphism (SNP) C936T of the vascular endothelial growth factor (VEGF) gene and the SNP C242T of the p22phox (CYBA) gene have been investigated in relation to DM2 and its complications. The aim of the present study was to investigate the association between these two SNPs and DM2, and also between the SNPs and the signs and symptoms of diabetic distal polyneuropathy. The DM2 group consisted of 98 individuals and the control group consisted of 104 individuals. The results demonstrated that there was no association between the different genotypes or alleles and increased risk of the disease (P>0.05). With SNP C242T, a significant association with body mass index between the CTxTT genotypes (P=0.043) was identified; and the greatest body mass indexes were among individuals with the TT genotype. An association between the degree of neuropathic symptoms and genotypic/allelic distribution of these polymorphisms was not observed. In conclusion, the investigated polymorphisms are not correlated with the risk of developing DM2. PMID- 26130420 TI - 21st century trucking: A trajectory for ergonomics and road freight. AB - Over the past decade there has been significant pressure to minimise emissions and safety risks related to commercial driving. This pressure to meet the triple bottom line of cost, environment, and society has often resulted in the rapid application of vehicle technologies designed to mitigate undesired effects. Often the cognitive and behavioural effects of technologies on the commercial driver have not received in-depth analysis to determine comprehensive viability. As such, this paper aims to identify a timescale for implementation for future technologies for UK road freight, and likely associated human factors issues, improving upon the currently employed 'trial-and-error' approach to implementation which may carry high economic, environmental, safety-related risk. Thought experiments are carried out to broadly explore these future systems. Furthermore, this work aims to examine whether technology alone will be enough to meet future CO2 reduction targets, and assess the role of behavioural and systems interventions for future research. PMID- 26130421 TI - Use of multi-velocity encoding 4D flow MRI to improve quantification of flow patterns in the aorta. AB - PURPOSE: To show that the use of a multi-velocity encoding (VENC) 4D-flow approach offers significant improvements in the characterization of complex flow in the aorta. Four-dimensional flow magnetic resonance imaging (MRI) (4D-flow) can be used to measure complex flow patterns and dynamics in the heart and major vessels. The quality of the information derived from these measures is dependent on the accuracy of the vector field, which is limited by the vector-to-noise ratio. MATERIALS AND METHODS: A 4D-flow protocol involving three different VENC values of 150, 60, and 20 cm/s was performed on six control subjects and nine patients with type-B chronic aortic dissection at 3T MRI. Data were processed using a single VENC value (150 cm/s) or using a fused dataset that selected the lowest appropriate VENC for each voxel. Performance was analyzed by measuring spatial vector angular correlation, magnitude correlation, temporal vector conservation, and "real-world" streamline tracing performance. RESULTS: The multi VENC approach provided a 31% improvement in spatial and 53% improvement in temporal precision of velocity vector measurements during the mid-late diastolic period, where 99% of the flow vectors in the normal aorta are below 20 cm/s. In low-flow conditions this resulted in practical improvements of greater than 50% in pathline tracking and streamline tracing quantified by streamline curvature measurements. CONCLUSION: A multi-VENC 4D-flow approach provides accurate vector data across normal physiological velocities observed in the aorta, dramatically improving outputs such as pathline tracking, streamline estimation, and further advanced analyses. PMID- 26130423 TI - Does Disposing of Construction and Demolition Debris in Unlined Landfills Impact Groundwater Quality? Evidence from 91 Landfill Sites in Florida. AB - More than 1,500 construction and demolition debris (CDD) landfills operate in the United States (U.S.), and U.S. federal regulations do not require containment features such as low-permeability liners and leachate collection systems for these facilities. Here we evaluate groundwater quality from samples collected in groundwater monitoring networks at 91 unlined, permitted CDD landfills in Florida, U.S. A total of 460,504 groundwater sample results were analyzed, with a median of 10 years of quarterly or semiannual monitoring data per site including more than 400 different chemical constituents. Downgradient concentrations of total dissolved solids, sulfate, chloride, iron, ammonia-nitrogen, and aluminum were greater than upgradient concentrations (p < 0.05). At downgradient wells where sulfate concentrations were greater than 150 mg/L (approximately 10% of the maximum dissolved sulfate concentration in water, which suggests the presence of leachate from the landfill), iron and arsenic were detected in 91% and 43% of samples, with median concentrations of 1,900 MUg/L and 11 MUg/L, respectively. These results show that although health-based standards can be exceeded at unlined CDD landfills, the magnitude of detected chemical concentrations is generally small and reflective of leached minerals from components (wood, concrete, and gypsum drywall) that comprise the bulk of discarded CDD by mass. PMID- 26130424 TI - Binuclear complexes of Ni(I) from 4-terphenyldithiophenol. AB - Binuclear complexes of Ni(i) have been prepared from a 4-terphenyldithiophenol ligand. Steric effects were found to determine the formation of coordination isomeric structures that differ in the nature of metal-to-ligand bonding. Coordination of spatially demanding phosphine ligands PR3, R = C6H6, C6H11, at nickel sites results in a butterfly shaped thiolate-bridged Ni2(MU-S)2 motif. For smaller PMe3, the central pi-system of the 4-terphenyl backbone adopts a bis allyl like MU-syn-eta(3):eta(3)-C6H4 structure due to significant d-pi* Ni(i)-to ligand charge transfer. Delocalisation indices delta(Ni-Ni) derived from DFT calculations provide a metric to assess the strength of electronic coupling of the Ni sites based on solid state structural data, and indicated less strong electronic coupling for the bis-allyl like structure with delta(Ni-Ni) = 0.225 as compared to 0.548 for the Ni2(MU-S)2 structural motif. A qualitative reactivity study toward CNCH3 as an auxiliary ligand has provided the first insight into the chemical properties of the bimetallic complexes presented. PMID- 26130425 TI - Outpatient surgery for unicompartmental knee arthroplasty is effective and safe. AB - PURPOSE: There has been increasing interest in accelerated programs for knee arthroplasty. We examined the efficacy and safety of an outpatient surgery (OS) pathway in patients undergoing unicompartmental knee arthroplasty (UKA). METHODS: This case-controlled study evaluates patients operated for UKA in an OS pathway (n = 20) compared to rapid recovery (RR), the current standard (n = 20). We investigated whether patients could be discharged on the day of surgery, resulting in comparable or better outcome by means of adverse events (AEs) in terms of pain (numerical rating scale, NRS), incidences of postoperative nausea and vomiting (PONV) and opiate use (<48 h postoperatively), complication and readmission rates (<3 months postoperatively). Patient-reported outcome measures (PROMS) were obtained preoperatively and 3 months postoperatively. RESULTS: Postoperative pain (NRS > 5) was the most common reason for prolonged hospital stay in the OS pathway. Eighty-five per cent of the patients were discharged on the day of surgery, whereas 95 % of the patients were discharged on postoperative day 3 in the RR pathway. Overall, median pain scores in both pathways did not exceed a NRS score of 5, without significant differences (RR vs. OS) in the number of patients with PONV (4 vs. 2) and opiate use (11 vs. 9) <48 h postoperatively. At 3 months postoperatively, no significant differences were found for AEs and PROMS between both pathways. CONCLUSION: The results of this study illustrates that an OS pathway for UKA is effective and safe with acceptable clinical outcome. Well-established and adequate standardized protocols, inclusion and exclusion criteria and a change in mindset for both the patient and the multidisciplinary team are the key factors for the implementation of an OS pathway. LEVEL OF EVIDENCE: Case-control study, Level III. PMID- 26130426 TI - Anatomic ACL reconstruction: the normal central tibial footprint position and a standardised technique for measuring tibial tunnel location on 3D CT. AB - PURPOSE: The aim of this study was to define the normal ACL central tibial footprint position and describe a standardised technique of measuring tibial tunnel location on 3D CT for anatomic single-bundle ACL reconstruction. METHODS: The central position of the ACL tibial attachment site was determined on 76 MRI scans of young individuals. The central footprint position was referenced in the anterior-posterior (A-P) and medial-lateral (M-L) planes on a grid system over the widest portion of the proximal tibia. 3D CT images of 26 young individuals had a simulated tibial tunnel centred within the bony landmarks of the ACL footprint, and the same grid system was applied over the widest portion of the proximal tibia. The MRI central footprint position was compared to the 3D CT central footprint position to validate the technique and results. RESULTS: The median age of the 76 MRI subjects was 24 years, with 32 females and 44 males. The ACL central footprint position was at 39 (+/-3 %) and 48 (+/-2 %), in the A-P and M-L planes, respectively. There was no significant difference in this position between sexes. The median age of the 26 CT subjects was 25.5 years, with 10 females and 16 males. The central position of the bony ACL footprint was at 38 (+/-2 %) and 48 (+/-2 %), in the A-P and M-L planes, respectively. The MRI and CT central footprint positions were not significantly different in relation to the medial position, but were different in relation to the anterior position (A-P 39 % vs. 38 %, p = 0.01). The absolute difference between the central MRI and CT reference positions was 0.45 mm. CONCLUSIONS: The ACL's normal central tibial footprint reference position has been defined, and the technique of measuring tibial tunnel location with a standardised grid system is described. This study will assist surgeons in evaluating tibial tunnel position in anatomic single bundle ACL reconstruction. LEVEL OF EVIDENCE: III. PMID- 26130427 TI - Model development to study strategies of younger and older adults getting up from the floor. AB - BACKGROUND: Long lies after a fall remain a public health challenge. Many successful fall prevention programmes have been developed but only few of them include recovery strategies after a fall. Once better understood, such movement strategies could be implemented into training interventions. AIMS: A model of motion sequences describing successful movement strategies for rising from the floor in different age groups was developed. Possible risk factors for poor rising performance such as flexibility and muscle power were evaluated. METHODS: Fourteen younger subjects between 20 and 50 years of age and 10 healthy older subjects (60+ years) were included. Movement strategies and key components of different rising sequences were determined from video analyses. The temporal parameters of transfers and number of components within the motion sequences were calculated. Possible explanatory variables for differences in rising performance were assessed (leg extension power, flexibility of the knee- and hip joints). RESULTS: Seven different components were identified for the lie-to-stand-walk transfer, labelled as lying, initiation, positioning, supporting, elevation, or stabilisation component followed by standing and/or walking. Median time to rise was significantly longer in older subjects (older 5.7s vs. younger 3.7s; p < 0.001), and leg extension power (left p = 0.002, right p = 0.013) and knee flexibility (left p = 0.019, right p = 0.025) were significantly lower. The number of components for rising was correlated with hip flexibility (r = 0.514) and maximal power (r = 0.582). The time to rise was correlated with minimal goniometric knee angle of the less flexible leg (r = 0.527) and maximal leg extension power (r = 0.725). CONCLUSIONS: A motion sequence model containing seven different components identified by individual key-frames could be established. Age-related differences in rising strategies and performance were identified. PMID- 26130428 TI - Decreased serum level of HMGB1 and MyD88 during human aging progress in healthy individuals. AB - AIMS: Previous studies have suggested that high mobility group box-1 protein (HMGB1) binds to the toll-like receptor 4 (TLR4) signaling mediates the progression of various inflammatory diseases. But the roles of HMGB1 and TLR4 in aging remain poorly unknown. In this study, we aimed to investigate the serum levels of HMGB1 and myeloid differentiation factor 88 (MyD88), which is one of TLR4's intracellular adaptor proteins during human aging process and their relevance with cathepsin B (CTSB). METHODS: This research was conducted using the blood samples provided by healthy people (n = 90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 25 years old, n = 30), middle age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of HMGB1, MyD88 and CTSB were measured using an enzyme linked immunosorbent assay. RESULTS: The serum levels of HMGB1 and MyD88 were significantly decreased in the aged group compared with those in the young group. Linear regression analysis showed that HMGB1 and MyD88 positively correlated with CTSB among the whole healthy people. A negative correlation was determined between MyD88 and age. CONCLUSIONS: The serum levels of HMGB1 and MyD88 significantly decreased with age. MyD88, but not HMGB1, was negatively correlated with age. PMID- 26130429 TI - Networking health: multi-level marketing of health products in Ghana. AB - Multi-level marketing (MLM0), a business model in which product distributors are compensated for enrolling further distributors as well as for selling products, has experienced dramatic growth in recent decades, especially in the so-called global South. This paper argues that the global success of MLM is due to its involvement in local health markets. While MLM has been subject to a number of critiques, few have analyzed the explicit health claims of MLM distributors. The majority of the products distributed through MLM are health products, which are presented as offering transformative health benefits. Based on interviews with MLM distributors in Ghana, but focusing on the experiences of one woman, this paper shows that MLM companies become intimately entwined with Ghanaian quests for health by providing their distributors with the materials to become informal health experts, allowing their distributors to present their products as medicines, and presenting MLM as an avenue to middle class cosmopolitanism. Ghanaian distributors promote MLM products as medically powerful, and the distribution of these products as an avenue to status and profit. As a result, individuals seeking health become a part of ethically questionable forms of medical provision based on the exploitation of personal relationships. The success of MLM therefore suggests that the health industry is at the forefront of transnational corporations' extraction of value from informal economies, drawing on features of health markets to monetize personal relationships. PMID- 26130430 TI - Leaving Nepal After the Earthquake: Sometimes Stepping Away May be the Best Disaster Response. PMID- 26130431 TI - The Occurrence Rate and Diameter of Arteries Traveling Near the Mandible and an Assessment of the Relative Hemorrhage Risk in Implant Surgery. AB - BACKGROUND: Bleeding in the floor of the mouth during implant surgery is attributed to arterial injuries in the sublingual space. PURPOSE: This study aimed to assess the relative hemorrhage risk during implant surgery. MATERIALS AND METHODS: We investigated the occurrence rate and diameter of submental and sublingual arteries with special reference to their relationship with the course patterns of these arteries using 26 human cadavers. RESULTS: Three types of arteries were distinguished: main duct (MD), mucoperiosteal branches (MB), and cortical branches (CB). The occurrence rate of MB and CB was significantly high at the central incisor region in the upper part of the mylohyoid muscle, whereas the diameter of the MB and CB was significantly smaller than the occurrence rate of MD at the incisor regions. The occurrence rate of MD in the submental artery was significantly higher at the lateral incisor, canine, and premolar regions in the lower parts, whereas the occurrence rate of MD was significantly lower at the second and third molars in the upper parts. CONCLUSION: The susceptibility of the submental artery to injury is suggested at the incisors, canine, premolars, and first molar regions during implant surgery. PMID- 26130432 TI - Ultrafast Photoinduced Electron Transfer and Charge Stabilization in Donor Acceptor Dyads Capable of Harvesting Near-Infrared Light. AB - To harvest energy from the near-infrared (near-IR) and infrared (IR) regions of the electromagnetic spectrum, which constitutes nearly 70 % of the solar radiation, there is a great demand for near-IR and IR light-absorbing sensitizers that are capable of undergoing ultrafast photoinduced electron transfer when connected to a suitable electron acceptor. Towards achieving this goal, in the present study, we report multistep syntheses of dyads derived from structurally modified BF2-chelated azadipyrromethene (ADP; to extend absorption and emission into the near-IR region) and fullerene as electron-donor and electron-acceptor entities, respectively. The newly synthesized dyads were fully characterized based on optical absorbance, fluorescence, geometry optimization, and electrochemical studies. The established energy level diagram revealed the possibility of electron transfer either from the singlet excited near-IR sensitizer or singlet excited fullerene. Femtosecond and nanosecond transient absorption studies were performed to gather evidence of excited state electron transfer and to evaluate the kinetics of charge separation and charge recombination processes. These studies revealed the occurrence of ultrafast photoinduced electron transfer leading to charge stabilization in the dyads, and populating the triplet states of ADP, benzanulated-ADP and benzanulated thiophene ADP in the respective dyads, and triplet state of C60 in the case of BF2 chelated dipyrromethene derived dyad during charge recombination. The present findings reveal that these sensitizers are suitable for harvesting light energy from the near-IR region of the solar spectrum and for building fast-responding optoelectronic devices operating under near-IR radiation input. PMID- 26130433 TI - Catheter-Directed Therapy is Safe and Effective for the Management of Acute Inferior Vena Cava Thrombosis. AB - BACKGROUND: The management of acute thrombosis of inferior vena cava (AT-IVC) has evolved to catheter-based therapies, the results of which remain uncertain. We report our institution's experience treating AT-IVC using endovascular methods. METHODS: A 10-year retrospective review of patients presenting with symptomatic IVC thrombosis between the years 2005 and 2014 was performed. Demographic data, treatment modalities, and outcomes were reviewed. RESULTS: Twenty-five patients (44% men) underwent treatment for acute (<2 weeks) symptomatic IVC thrombosis. Presenting symptoms included pain and limb swelling in 23 (92%), motor dysfunction in 16 (64%), sensory loss in 14 (56%), and pulmonary embolism (PE) in 2 (8%) patients. Phlegmasia cerulea dolens was present in 5 patients, a history of malignancy was identified in 7 patients, and 21 patients had an IVC filter at presentation (Trapease 12, G2X 3, Option 2, Eclipse 2, Meridian 2). Four patients had a documented hypercoagulable state, 21 patients underwent venous angioplasty, and 7 (28%) patients underwent venous stenting of the IVC or iliofemoral veins. Significant (>50% luminal gain) angiographic resolution of venous thrombus was achieved in all 25 patients. Twenty-one (84%) patients reported moderate-to complete symptomatic improvement immediately after completion of the procedures. Two patients had a clinically symptomatic PE and 1 patient underwent an above knee amputation secondary to venous gangrene. Other complications included 6 minor bleeding complications (2 local hematoma, 4 hematuria) all of which resolved spontaneously. There were 2 major bleeding complications (1 disseminated intravascular coagulation, 1 retroperitoneal hematoma). CONCLUSIONS: Endovascular treatment of AT-IVC, regardless of etiology, is safe and effective with excellent short-term clinical results. An aggressive endovascular approach to treatment of AT-IVC is warranted even in the presence of a thrombosed vena cava filter. PMID- 26130434 TI - Yield of Graft Surveillance after Open Aortic Operations. AB - BACKGROUND: To examine the value of routine postoperative surveillance duplex in identifying late graft-related complications after open aortic operations for occlusive and aneurysmal disease. METHODS: All open aortic operations performed at a single institution between 1998 and 2012 were retrospectively reviewed. All patients were scheduled for yearly postoperative surveillance duplex. Patients who had at least 30-day follow-up and at least 1 surveillance duplex were analyzed. RESULTS: Two hundred thirty-eight open aortic operations were performed during the study period, 140 of which met the inclusion criteria. Mean follow-up was 3.9 years. A tube graft was performed in 65 (46%), and the proximal anastomosis was in the infrarenal or juxtarenal position in 126 (90%). Overall survival at was 100% and 85.3% at 1 and 5 years, respectively. A mean of three surveillance duplexes was performed per patient. Surveillance duplex scanning identified 31 significant findings in 31 patients, including 13 significant velocity increases (>3:1) and 18 aneurysms/pseudoaneurysms. Thirteen (9%) patients required a graft-related operation at a mean of 3.5 years. Indications included anastomotic aneurysm/pseudoaneurysm (n = 7), limb occlusion (n = 3), graft stenosis (n = 2), and graft infection (n = 1). The indication for operation was identified by surveillance duplex in 5 of the 13 cases. The remainder were identified by physical examination and/or clinical presentation. Reintervention free survival (RIFS) was 98.5% at 1 year and 80.4% at 5 years. On multivariable analysis, RIFS was improved only by the use of a tube graft during the index operation (hazard ratio, 0.73; 95% confidence interval, 0.54-0.96). CONCLUSIONS: Routine surveillance duplex identifies few findings that lead to reintervention. Patients with a non-tube-graft reconstruction are at greater risk for reintervention and may benefit from surveillance duplex after open aortic operations. PMID- 26130435 TI - MATERNAL DEPRESSION AND CHILD OXYTOCIN RESPONSE; MODERATION BY MATERNAL OXYTOCIN AND RELATIONAL BEHAVIOR. AB - BACKGROUND: Maternal postpartum depression (PPD) carries long-term detrimental effects on children's well-being, yet the mechanisms of transmission remain unclear. One possible pathway of vulnerability involves the oxytocinergic (OT) system, which is transferred from mother to child via sensitive caregiving and is disrupted in PPD. METHOD: A large birth cohort (N = 1983) of women were repeatedly assessed for depression from birth to 6 years. Utilizing an extreme case design, two matched cohorts were formed; mothers chronically depressed from birth to 6 years and nondepressed controls (N = 97, depressed = 41, nondepressed; N = 56). At 6 years, mothers and children underwent psychiatric diagnosis, urinary OT was assayed from mother and child before and after social contact, and mother-child interactions were coded. RESULTS: Baseline OT and OT response of mother and child were interrelated and children of depressed mothers showed low baseline OT and attenuated OT response. Child OT response was negatively predicted by maternal depression, child Axis-I psychopathology, maternal expressed negative affect, and child social withdrawal. Interaction effect of maternal baseline OT and depression emerged. Slope analysis indicated that when maternal OT was medium or low, child OT response was negatively impacted by maternal depression. However, when maternal OT was high, child OT was unaffected, suggesting that maternal OT functionality buffers the effects of depression on the child. CONCLUSION: Results suggest involvement of the OT system in the cross generational transfer of vulnerability, as well as resilience, from depressed mothers to their children. Because the OT system is open to interventions that enhance maternal touch and contact, findings have important implications for targeted early dyadic inventions. PMID- 26130437 TI - Author's reply. PMID- 26130436 TI - Emergency pancreaticoduodenectomy: When is it needed? A dual non-trauma centre experience and literature review. AB - INTRODUCTION: Emergency pancreaticoduodenectomy (EPD) has been very rarely reported in literature as a lifesaving procedure for complex pancreatic injury, uncontrollable hemorrhage from ulcers and tumors, descending duodenal perforations, and severe infection. The aim of this study was to analyze the experience of two non-trauma centers and to review the literature concerning emergency pancreaticoduodenectomy. METHODS: From January 2005 to December 2014, from a population of 169 PD (92 females and 77 males; mean age: 61.3, range 23 81) 5 patients (3%; 2 females and 3 males; mean age: 57.8, range: 42-74) underwent EPD for non-traumatic disease performed at two Academic Units of the University of Bari. RESULTS: The emergency pancreaticoduodenectomy subgroup of patients showed an overall morbidity of 80%, and mortality of 40%. In 80% (4/5) of patients treated by emergency pancreaticoduodenectomy, the pancreatic remnant was not reconstructed, and in 20% (1/5) a pancreaticojejunostomy was performed. CONCLUSION: Emergency pancreaticoduodenectomy is an effective life-saving operation reservable to pancreatoduodenal trauma, perforations, and bleeding, unmanageable by a less invasive approach. It should be preferentially approached by surgeons with a high level of experience in hepatobiliary and pancreatic surgery and in trauma centers too, but it should also be in the armamentarium of general surgeons performing hepato-pancreato-biliary surgery. PMID- 26130438 TI - Radiographic diagnosis of sagittal plane rotational displacement in pelvic fractures: a cadaveric model and clinical case study. AB - PURPOSES: Our objective was to measure the sagittal plane rotational (flexion and extension) displacement of hemipelvis radiologically and analyze the ratio of flexion and extension displacement of unstable pelvic fractures. METHODS: We used 8 cadaveric models to study the radiographic evidence of pelvic fractures in the sagittal plane. We performed pelvic osteotomy on 8 cadavers to simulate anterior and posterior pelvic ring injury. Radiological data were measured in the flexion and extension group under different angles (5 degrees , 10 degrees , 15 degrees , 20 degrees , and 25 degrees ). We retrospectively reviewed 164 patients who were diagnosed with a unilateral fracture of the pelvis. Pelvic ring displacement was identified and recorded radiographically in cadaveric models. RESULTS: The flexion and extension displacement of pelvic fractures was measured in terms of the vertical distance of fracture from the top of iliac crest to the pubic tubercle (CD) or from the top of iliac crest to the lowest point of ischial tuberosity (AB). Fifty-seven pelves showed flexion displacement and 15 showed extension displacement. Closed reduction including internal fixation and external fixation was successfully used in 141 cases (86.0 %). The success rates of closed reduction in flexion and extension displacement groups were 77 and 73 %, respectively, which were lower than in unstable pelvic ring fractures. CONCLUSIONS: The sagittal plane rotation (flexion and extension) displacement of pelvic fractures could be measured by special points and lines on the radiographs. Minimally invasive reduction should be based on clearly identified differences between the sagittal plane rotation and the vertical displacement of pelvic fractures. PMID- 26130439 TI - Human telomerase inhibitors from microbial source. AB - Telomerase enzyme inhibitors have gained attention of scientific field due to the specificity of action of telomerase based therapies. Some telomerase have good combinatorial action with certain DNA damaging drugs. Natural compounds isolated from microbes provide a new scope of screening and large scale production of telomerase inhibitors. This review emphasizes the biochemistry and mode of action of different types of telomerase inhibitors isolated from microbial sources. Also elaborates on classification of telomerase inhibitors based on their mode of action in cancer cells. PMID- 26130440 TI - The potential protein kinase A (Pka) phosphorylation site is required for the function of FgSge1 in Fusarium graminearum. AB - The new transcription factor Sge1 has garnered much attention in filamentous fungi recently, which highlights its role in pathogenicity, conidiation, and the production of secondary metabolites. In this study, we demonstrated that FgSge1 is localized in the nucleus in Fusarium graminearum using fluorescent protein GFP. Mutants containing a T67A mutation within the potential protein kinase A (Pka) phosphorylation site of FgSge1 exhibited a significant decrease in conidiation and dramatically impaired virulence on both wheat head and non-host tomato. These results indicated that the Pka phosphorylation site is required for the function of FgSge1 in F. graminearum. In addition, we characterized the FgSGE1 deletion mutants and found that the mutants showed increased sensitivity to osmotic stress mediated by NaCl or KCl, and to cell wall damaging agent congo red (CR). Real-time PCR assays revealed increased transcription levels of FgSGE1 with the treatment of NaCl or CR, and decreased FgSGE1 transcription in the FgOS 2 deletion mutant DeltaFgOs-2. Based on the transcription levels, it can be concluded that FgSge1 is a downstream target of the mitogen-activated protein kinase FgOs-2. PMID- 26130442 TI - Seven UK medical students studying in Sudan may be heading for Syria. PMID- 26130441 TI - Comparison of gadoxetic acid-enhanced magnetic resonance imaging and contrast enhanced computed tomography with histopathological examinations for the identification of hepatocellular carcinoma: a multicenter phase III study. AB - BACKGROUND: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) has an important role in preoperative evaluation of hepatocellular carcinoma (HCC). However, no studies have prospectively performed intraindividual comparison of gadoxetic acid-enhanced 3T MRI and multidetector-row computed tomography (MDCT) with histopathological examination for the detection of HCCs. We prospectively compared the efficacies of gadoxetic acid-enhanced MRI and multiphasic contrast enhanced MDCT with that of histopathological examination, used as a reference standard, for the detection of HCC in surgical candidates. METHODS: The study was approved by the institutional review boards at each of four centers. Patients scheduled to undergo multiphasic CT, gadoxetic acid-enhanced MRI, and liver surgery were prospectively included in this study. The diagnostic abilities of MRI and CT were evaluated and compared on the basis of sensitivity and positive predictive value for detection of and differentiation between HCCs and benign lesions. RESULTS: Fifty-four patients with 83 histopathologically confirmed HCCs were included in the study. Combined interpretation of the dynamic and hepatobiliary phases of gadoxetic acid-enhanced MRI showed statistically higher sensitivity for lesion detection (83 %) than did interpretation of multiphasic MDCT images (70 %; p < 0.001). The mean area under each alternative free-response receiver operating characteristics curve was significantly higher for MR images (0.927) than for CT images (0.864, p < 0.01). CONCLUSIONS: The sensitivity for preoperative detection of HCCs was higher for gadoxetic acid-enhanced MRI than for multiphasic MDCT imaging. PMID- 26130443 TI - Variation in readmission rates by emergency departments and emergency department providers caring for patients after discharge. AB - BACKGROUND: The role of the emergency department (ED) provider and ED facility in readmissions of recently discharged patients who visit the ED has not been studied. OBJECTIVE: To determine the variation in readmission rates by ED facility and ED providers caring for patients after discharge. DESIGN: Retrospective cohort study using multilevel, multivariable models of 100% Texas Medicare claims data from the years 2007 to 2011. SETTING: Texas acute-care hospitals and ED facilities. PATIENTS: Medicare beneficiaries who visited an ED within 30 days of discharge from a hospital. INTERVENTION: None. MEASUREMENT: Readmission after an ED visit within 30 days of discharge from an initial hospitalization defined as a hospitalization starting the day of or the day following the ED visit. RESULTS: The mean readmission rate following an ED visit was 52.67%. In 2-level models, 14.2% of ED providers readmitted significantly more patients (mean readmission rate of 67.2%) than the mean; 14.7% of ED providers readmitted significantly fewer patients (mean readmission rate of 36.8%) than the mean. After accounting for the ED facility in 3-level models, the variance for the ED providers decreased 65% from 0.2532 to 0.0893. CONCLUSIONS: The risk of readmission varies by ED provider caring for patients after discharge. A large part of this variation is explained by the ED facility in which the ED providers practice. Thus, ED provider practices patterns and ED facility systems of care may be a target for interventions to reduce readmissions. PMID- 26130444 TI - Positive human contact on the first day of life alters the piglet's behavioural response to humans and husbandry practices. AB - This experiment examined the effects of positive human contact at suckling on the first day of life on the behavioural and physiological responses of piglets to both humans and routine husbandry procedures. Forty litters from multiparous sows were randomly allocated to one of two treatments: Control (CC, minimal human interaction with day-old piglets) or Positive Contact (PC, human talking and caressing piglets during 6 suckling bouts on their first day of life, day 1). In each litter, 2 males and 2 females were randomly selected and their behavioural responses to tail docking (day 2), and to an experimenter (day 35) were studied. Escape behaviour at tail docking was assessed according to intensity (on a scale from 0 to 4 representing no movement to high intensity movement) and duration (on a scale from 0 to 3 representing no movement to continuous movement). At day 15 of age, a human approach and avoidance test was performed on focal piglets and at day 15, escape behaviour to capture before and after testing was recorded again. Blood samples for cortisol analysis were obtained from the focal piglets 30 min after tail docking and 1 h after weaning. Escape behaviour to tail docking of the PC piglets was of shorter duration than that of the CC piglets (P = 0.05). There was a tendency for the escape behaviour both before and after testing at day 15 to be of a lower intensity (P = 0.11 and P = 0.06, respectively) and a shorter duration (P = 0.06 and P = 0.08, respectively) in the PC piglets. There was a tendency for PC piglets to have higher cortisol concentrations after tail docking than the CC piglets (P = 0.07). Male piglets had higher cortisol concentrations after tail docking and after weaning than female piglets (P = 0.02 and P = 0.03). The results indicate that Positive Contact treatment reduced the duration of escape behaviour of piglets to tail docking. The role of classical conditioning, habituation and developmental changes in the observed effects of the Positive Contact treatment is unclear. Nonetheless, this experiment demonstrated that brief positive human contacts early in life can alter the behavioural responses of piglets to subsequent stressful events. PMID- 26130445 TI - Ontogeny of the corticotrophin-releasing hormone system in slow- and fast-growing chicks (Gallus gallus). AB - Selective breeding has caused striking phenotypic differences among chickens. For example, the broiler, a fast-growing phenotype, is a relatively heavy bird selected for meat production while the layer, a slower-growing, lighter bird, was developed for egg production. Broilers are prone to early obesity and show physiological and behavioural differences in response to stressors compared with layers. However, the genetic causes of the differences in the responses to stressors between them have not been determined. The purpose of the present study was to compare the ontogeny of the corticotropin-releasing hormone (CRH) system between broilers and layers, because the CRH system plays a major role in regulating stress. We found that fast-growing broilers showed significantly lower levels of diencephalic CRH mRNA expression at post-hatch days 8 and 15 and pituitary CRH receptor 1 mRNA expression from the embryonic to post-hatch stage than slower-growing layers. However, a significantly higher level of CRH-binding protein (CRH-BP), which inactivates CRH and prevents pituitary-adrenal stimulation, was found in broilers compared with layers. Indeed, broilers showed significantly lower levels of plasma corticosterone (CORT) than layers. Subjecting birds to isolation stress did not alter the CORT level of broilers, but increased that of layers. Collectively, the stress-coping actions of the CRH system via the hypothalamic-pituitary-adrenal (HPA) axis might be less responsive in broilers than in layers due to differential gene expression. Together, the present results provide evidence that genetic selection has altered gene expression in the CRH system of the fast-growing broiler, causing blunted HPA axis activity in response to stressors. PMID- 26130446 TI - Fluid-fluid levels in lateral ventricles predict bacterial CNS infections. PMID- 26130447 TI - Primary writing tremor is a dystonic trait: Evidence from an instructive family. PMID- 26130448 TI - Multiple sclerosis and breast cancer. AB - Multiple sclerosis (MS) and breast cancer (BC) share common features; most notably, both are more frequent in women than in men. In addition to the involvement of sex hormones, a number of genetic and pharmacological studies support a possible relationship between these two diseases. However, there are no conclusive epidemiological findings related to MS and BC worldwide, and there are no recent data for the US population. We conducted a case-control study using a hospital inpatient discharge dataset (21,536 cases and two control series totaling 59,581 controls) from the Texas Health Care Information Collection. We assessed occurrence of MS in BC cases and in two control series: diabetes mellitus type II, and open wounds. After controlling for age, race-ethnicity, and health insurance status, a statistically-significant protective association was detected: BC cases were 45% less likely than diabetic controls to have MS (OR=0.55, 95% CI=0.37-0.81), and 63% less likely than open wound controls to have MS (OR=0.37, 95% CI=0.21-0.66). Our study presented here is the only current assessment of the association between MS and BC in the USA and suggests a protective effect of MS on BC in the hospitalized population. PMID- 26130449 TI - Price-related promotions for tobacco products on Twitter. AB - OBJECTIVES: This cross-sectional study examined price-related promotions for tobacco products on Twitter. METHODS: Through the Twitter Firehose, we obtained access to all public tweets posted between 6 December 2012 and 20 June 2013 that contained a keyword suggesting a tobacco-related product or behaviour (eg, cigarette, vaping) in addition to a keyword suggesting a price promotion (eg, coupon, discount). From this data set of 155 249 tweets, we constructed a stratified sampling frame based on the price-related keywords and randomly sampled 5000 tweets (3.2%). Tweets were coded for product type and promotion type. Non-English tweets and tweets unrelated to a tobacco or cessation price promotion were excluded, leaving an analytic sample of 2847 tweets. RESULTS: The majority of tweets (97.0%) mentioned tobacco products while 3% mentioned tobacco cessation products. E-cigarettes were the most frequently mentioned product (90.1%), followed by cigarettes (5.4%). The most common type of price promotion mentioned across all products was a discount. About a third of all e-cigarette related tweets included a discount code. Banned or restricted price promotions comprised about 3% of cigarette-related tweets. CONCLUSIONS: This study demonstrates that the vast majority of tweets offering price promotions focus on e-cigarettes. Future studies should examine the extent to which Twitter users, particularly youth, notice or engage with these price promotion tweets. PMID- 26130450 TI - Characterization of Three Tetrabromobisphenol-S Derivatives in Mollusks from Chinese Bohai Sea: A Strategy for Novel Brominated Contaminants Identification. AB - Identification of novel brominated contaminants in the environment, especially the derivatives and byproducts of brominated flame retardants (BFRs), has become a wide concern because of their adverse effects on human health. Herein, we qualitatively and quantitatively identified three byproducts of tetrabromobisphenol-S bis(2,3-dibromopropyl ether) (TBBPS-BDBPE), including TBBPS mono(allyl ether) (TBBPS-MAE), TBBPS mono(2-bromoallyl ether) (TBBPS-MBAE) and TBBPS mono(2,3-dibromopropyl ether) (TBBPS-MDBPE) as novel brominated contaminants. Meanwhile, the mass spectra and analytical method for determination of TBBPS-BDBPE byproducts were presented for the first time. The detectable concentrations (dry weight) of TBBPS-MAE, TBBPS-MBAE and TBBPS-MDBPE were in the ranges 28-394 MUg/g in technical TBBPS-BDBPE and 0.1-4.1 ng/g in mollusks collected from the Chinese Bohai Sea. The detection frequencies in mollusk samples were 5%, 39%, 95% for TBBPS-MAE, TBBPS-MBAE and TBBPS-MDBPE, respectively, indicating their prevailing in the environment. The results showed that they could be co-produced and leaked into the environment with production process, and might be more bioaccumulative and toxic than TBBPS-BDBPE. Therefore, the production and use of TBBPS derivatives lead to unexpected contamination to the surrounding environment. This study also provided an effective approach for identification of novel contaminants in the environment with synthesized standards and Orbitrap high resolution mass spectrometry. PMID- 26130451 TI - Impact of adjuvant chemotherapy on patients with pathological Stage T3b and/or lymph node metastatic bladder cancer after radical cystectomy. AB - OBJECTIVE: To evaluate the effectiveness of adjuvant chemotherapy in patients with pathological Stage T3 bladder cancer who had undergone radical cystectomy, and to determine the prognostic survival factors for adjuvant chemotherapy treatment. METHODS: From January 1990 to October 2013, 202 patients underwent radical cystectomy and pelvic lymphadenectomy. Among them, 65 patients with non organ-confined disease (pT3, N0-3, M0) diagnosed were investigated in this study. Thirty-one patients (48%) were treated with adjuvant chemotherapy and the remaining 34 patients (52%) were not. RESULTS: Median age of all patients was 66 years, and median follow-up was 26.1 months. For all pT3 patients, overall survival and disease-free survival times were similar in the adjuvant chemotherapy and non-adjuvant chemotherapy groups. However, in the pT3b subgroup, median overall survival (47.0 vs. 10.6 months) and median disease-free survival (35.5 vs. 5.3 months) times were significantly prolonged for those who underwent adjuvant chemotherapy (P = 0.009 and 0.025). In patients with pathological lymph node metastatic (pN+), median overall survival (30.1 vs. 6.4 months) and median disease-free survival (15.7 vs. 3.5 months) times were significantly prolonged in the adjuvant chemotherapy group (P = 0.016 and 0.027). In addition, according to multivariate analysis in pT3b and/or pN+ subgroup patients, adjuvant chemotherapy status was an independent predictive factor for overall survival and disease-free survival. CONCLUSION: Adjuvant chemotherapy did not significantly improve overall survival and disease-free survival when compared with all patients with pT3 who had received radical cystectomy in the non-adjuvant chemotherapy group. However, in the pT3b and pN+ subgroup, adjuvant chemotherapy demonstrated statistically significant benefits regarding overall survival and disease-free survival. Although these results could not support adjuvant chemotherapy use for all pT3 patients, the pT3b substage and/or pN+ may help identify patients with pT3 who could benefit from adjuvant chemotherapy. PMID- 26130452 TI - Development and validation of a microfluidic immunoassay capable of multiplexing parallel samples in microliter volumes. AB - Immunoassays are widely utilized due to their ability to quantify a vast assortment of biomolecules relevant to biological research and clinical diagnostics. Recently, immunoassay capabilities have been improved by the development of multiplex assays that simultaneously measure multiple analytes in a single sample. However, these assays are hindered by high costs of reagents and relatively large sample requirements. For example, in vitro screening systems currently dedicate individual wells to each time point of interest and this limitation is amplified in screening studies when the investigation of many experimental conditions is necessary; resulting in large volumes for analysis, a correspondingly high cost and a limited temporal experimental design. Microfluidics based immunoassays have been developed in order to overcome these drawbacks. Together, previous studies have demonstrated on-chip assays with either a large dynamic range, high performance sensitivity, and/or the ability to process samples in parallel on a single chip. In this report, we develop a multiplex immunoassay possessing all of these parallel characteristics using commercially available reagents, which allows the analytes of interest to be easily changed. The device presented can measure 6 proteins in 32 samples simultaneously using only 4.2 MUL of sample volume. High quality standard curves are generated for all 6 analytes included in the analysis, and spiked samples are quantified throughout the working range of the assay. In addition, we demonstrate a strong correlation (R(2) = 0.8999) between in vitro supernatant measurements using our device and those obtained from a bench-top multiplex immunoassay. Finally, we describe cytokine secretion in an in vitro inflammatory hippocampus culture system, establishing proof-of-concept of the ability to use this platform as an in vitro screening tool. The low-volume, multiplexing abilities of the microdevice described in this report could be broadly applied to numerous situations where sample volumes and costs are limiting. PMID- 26130453 TI - Assessment of Clinical Complete Response After Chemoradiation for Rectal Cancer with Digital Rectal Examination, Endoscopy, and MRI. PMID- 26130454 TI - The Effect of Molecular Subtype and Residual Disease on Locoregional Recurrence in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Postmastectomy Radiation. AB - BACKGROUND: The relative contribution of biologic subtype to locoregional recurrence (LRR) in patients treated with neoadjuvant chemotherapy (NAC), mastectomy, and postmastectomy radiotherapy (PMRT) is not clearly defined. METHODS: 233 patients with stages 2 and 3 breast cancer who received NAC, mastectomy, and PMRT between 2000 and 2009 were included: 53 % (n = 123) had HR+ (ER or PR+/HER2-), 23 % (n = 53) had HER2+ (HER2+/HR+ or HR-), and 24 % (n = 57) had triple-negative (TN) disease (HR-/HER2-). The 5-year LRR rates were estimated by Kaplan-Meier methods. Cox regression analysis was performed to evaluate covariates associated with LRR. RESULTS: The median follow-up period was 62 months. A pathologic complete response (pCR) was seen in 14 % of the patients. The 5-year LRR rate was 8 % for the entire cohort. The LRR rate was 0 % for the patients with a pCR versus 9 % for the patients without a pCR (p = 0.05). TN disease [Hazard ratio (HR) 4.4; p = 0.003] and pathologic node positivity (HR 9.8; p = 0.03) were associated with LRR. Patients with TN disease had a higher LRR rate than patients with HER2+ or HR+ disease (20 vs. 6 and 4 %; p = 0.005). Among patients without a pCR, TN subtype was associated with increased LRR risk (26 versus 7 % HER+ and 4 % HR+; p < 0.001). CONCLUSIONS: Patients with TN breast cancer had the highest LRR rate after NAC, mastectomy and PMRT. Whereas no LRR was observed among TN patients with a pCR, TN patients with residual disease had a significantly higher LRR risk. Patients with HR+ and HER2+ breast cancer had favorable LRR rates regardless of NAC response, likely due to receipt of adjuvant systemic targeted therapies. PMID- 26130455 TI - The Fate of Organophosphorus Pesticides during Camellia Oil Production. AB - The purpose of this study was to investigate the fate of organophosphorus pesticides (OPs) during camellia oil production process, from camellia fruit to the final oil product. The results showed that the OPs were mainly distributed in the peel of camellia fruit, basically above 40% after the pesticide application of 7 d (P < 0.05). A small amount of OPs could enter into the seed and convert to crude camellia oil, with the concentration of 19.5 to 548.2 mg/L. In addition, metabolites of OPs (25.7 to 768.9 mg/L) could be detected in the crude camellia oil. Moreover, the refining process (degumming, deacidfying, bleaching) had a significant effect on the removal of OPs from the crude camellia oil (P < 0.05), and the effect was related to the octanol-water partition constant (LogP) of pesticide. The larger the LogP, the more stable the OPs were during refining process. The final refined camellia oil was found to have no detectable levels of OPs metabolite. PMID- 26130456 TI - Recent progress in sustainable polymers obtained from cyclic terpenes: synthesis, properties, and application potential. AB - The functionalization and polymerization of biobased monocyclic terpenes and their derivatives for the synthesis of sustainable polymers is described, especially in view of the synthetic routes and properties of the obtained macromolecular architectures. Comparison of these procedures and the obtained materials with "classical" oil-based approaches, and also with alternative biobased routes, gives interesting insights into the potential of these small terpene building-block structures for modern polymer science and technology. PMID- 26130457 TI - Combined experimental and theoretical study on the removal of pollutant compounds by peroxidases: affinity and reactivity toward a bioremediation catalyst. AB - Water pollution is a significant and growing problem throughout the world, especially in developing countries. In order to minimize environmental problems, catalysts have increasingly been designed to remove pollutants from the water. In an attempt to innovate by the creation of new low-cost alternatives to efficiently remove pollutants, the enzymatic treatment has been intensely studied for this purpose. Reactions catalyzed by enzymes are able to perform specific treatments, commonly with high rates of the final products. With this, the enzyme, peroxidase, is a promising candidate as a bioremediation catalyst. The efficiency of oxidoreductive enzymes, such as horseradish peroxidase (HRP) and soybean peroxidase (SP) have been studied, given that their performance depends on the substrate. In this investigation, experimental techniques and theoretical calculations have been employed in order to investigate the oxidative process for the ferulic acid and bromophenol blue dyes, performed by HRP and SP. Both enzymes showed a comparable behavior with respect to ferulic acid substrate. On the other hand, by utilizing bromophenol blue dye as a substrate, the behavior of the employed catalysts was significantly different. Experimental data have shown that HRP was more active toward bromophenol blue when compared to ferulic acid, being more rapidly degraded by the HRP enzyme. This tendency was confirmed by our theoretical docking, PM6 semi-empirical method, and DFT calculation results, in which the interaction, binding energies, and transition states were determined. PMID- 26130458 TI - Interventricular septum hydatid cyst presenting with acute lower limb ischemia: a case report. AB - Cardiac hydatid cysts are rarely seen. The presentation of an acute lower limb ischemia secondary to embolization from an interventricular hydatic cyst is also rare. We describe a case of a 30-year-old-man who presented with acute lower limb ischemia revealing hydatid cyst of the interventricular septum and septal defect, and who was operated on successfully. PMID- 26130460 TI - Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer. AB - PURPOSE: To investigate the value of the metabolic tumor response assessed with (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC). EXPERIMENTAL DESIGN: Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (DeltaSUVmax) were assessed using FDG-PET. RESULTS: The pCR rate was 42%. High Ki-67 proliferation index (P = 0.016), negative EGFR status (P = 0.042), and high DeltaSUVmax (P = 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P = 0.043) and high DeltaSUVmax (OR, 7.1; P = 0.014) were independent predictors of pCR. Using a threshold at -50%, tumor DeltaSUVmax predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low DeltaSUVmax and positive EGFR status could predict non-pCR with an accuracy of 92%. CONCLUSIONS: It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials. Clin Cancer Res; 21(24); 5460 8. (c)2015 AACR. PMID- 26130461 TI - Evaluation of Epigenetic Drug Targeting of Heterogenous Tumor Cell Fractions Using Potential Biomarkers of Response in Ovarian Cancer. AB - PURPOSE: Resolution of aberrant epigenetic changes leading to altered gene expression during transformation and tumor progression is pertinent for mechanistic understanding of disrupted pathways in cancer. Such changes provide for biomarkers that can be applied in drug screening and improved disease management. EXPERIMENTAL DESIGN: Genome-wide profiling and analyses of promoter DNA methylation, histone modifications, and gene expression of an in vitro progression model of serous ovarian adenocarcinoma were carried out. Similar in silico analyses and comparison of methylation and gene expression of early- and late-grade ovarian cancer samples in The Cancer Genome Atlas assigned a clinical relevance to our study. Candidate biomarkers were evaluated for epigenetic drug treatments in experimental animal models on a background of differing tumor cell responses arising from intratumor heterogeneity. RESULTS: Differentially regulated genes during tumor progression were identified through the previously mentioned analyses as candidate biomarkers. In examining the tumor suppressor PTGIS as a potential biomarker for treatment with either 5-Aza-dC or TSA, 5-Aza dC effectively stabilized cell cycling, restricted genetic instability, and derepressed PTGIS expression, while TSA led to emergence of drug-resistant progenitors lacking PTGIS expression. Profiling MEST and RXRgamma for curcumin and CBB1007, respectively, indicated an inability of curcumin and CBB1007 in restricting residual tumor regenerative capabilities. CONCLUSIONS: Our study provides novel insights into epigenetic regulation in ovarian cancer progression and potential biomarkers for evaluating efficacy of epigenetic drugs in restricting residual tumor regeneration. Such approaches may assign a new functional interpretation of drug efficacy and cell tumor responses in ovarian cancer. PMID- 26130459 TI - DYNC2LI1 mutations broaden the clinical spectrum of dynein-2 defects. AB - Skeletal ciliopathies are a heterogeneous group of autosomal recessive osteochondrodysplasias caused by defects in formation, maintenance and function of the primary cilium. Mutations in the underlying genes affect the molecular motors, intraflagellar transport complexes (IFT), or the basal body. The more severe phenotypes are caused by defects of genes of the dynein-2 complex, where mutations in DYNC2H1, WDR34 and WDR60 have been identified. In a patient with a Jeune-like phenotype we performed exome sequencing and identified compound heterozygous missense and nonsense mutations in DYNC2LI1 segregating with the phenotype. DYNC2LI1 is ubiquitously expressed and interacts with DYNC2H1 to form the dynein-2 complex important for retrograde IFT. Using DYNC2LI1 siRNA knockdown in fibroblasts we identified a significantly reduced cilia length proposed to affect cilia function. In addition, depletion of DYNC2LI1 induced altered cilia morphology with broadened ciliary tips and accumulation of IFT-B complex proteins in accordance with retrograde IFT defects. Our results expand the clinical spectrum of ciliopathies caused by defects of the dynein-2 complex. PMID- 26130462 TI - Palladium-Catalyzed Direct C-H Arylation of Isoxazoles at the 5-Position. AB - A palladium-catalyzed direct arylation of isoxazoles with aryl iodides has been achieved. The C-H bond at the 5-position is activated selectively to give coupling products in moderate to good yields. This direct arylation was applied to the synthesis of a spiro-type chiral ligand, which proved to be most effective to the palladium-catalyzed tandem cyclization of a dialkenyl alcohol. PMID- 26130463 TI - Optimizing fluorescent protein trios for 3-Way FRET imaging of protein interactions in living cells. AB - Powerful new methods have extended FRET microscopy to the imaging of three or more interacting proteins inside living cells. Here, we compared widely available fluorescent proteins to find the best trio for 3-Way FRET imaging. We focused on readily available cyan, yellow, and red proteins that have high quantum yields, large extinction coefficients and good photostability, which defined these candidate proteins: CyPet/mTFP1/mTurqoise2, mCitrine/YPet, and TagRFP/TagRFPt/mRuby2/mCherry. By taking advantage of the high structural similarity across the fluorescent proteins, we generated structurally similar, but photophysically distinct donor/acceptor and triple fluorophore fusion proteins and measured their FRET efficiencies inside living cells. Surprisingly, their published photophysical parameters and calculated Forster distances did not predict the best combinations of FPs. Using cycloheximide to inhibit protein synthesis, we found that the different FP maturation rates had a strong effect on the FRET efficiency. This effect was pronounced when comparing rapidly maturing yellow and slowly maturing red FPs. We found that red FPs with inferior photophysics gave superior FRET efficiencies because of faster maturation rates. Based on combined metrics for the FRET efficiency, fluorophore photophysics and fluorophore maturation we determined that Turqoise2, YPet and Cherry were the best available FPs for live cell 3-Way FRET measurements. PMID- 26130464 TI - Examination of the Perceptions of Registered Nurses Regarding the Use of Healing Touch in the Acute Care Setting. AB - Given the current transformation of traditional health care to provide more integrative and complementary modalities, health systems are implementing new programs and services to meet consumer and provider needs. One such integrative modality, Healing Touch, with a foundation in holistic nursing, is a gentle therapy that uses touch to promote health and well-being by balancing the human energy system. This article describes the perceptions of registered nurses regarding the implementation of a Healing Touch training program at a multihospital health system. Five themes were identified: benefit to the patient, benefit to the nurse, holism beyond task orientation, integrating Healing Touch into acute care, and barriers and challenges. Nurses recognize the importance of creating caring-healing relationships and a holistic approach to care. Training in Healing Touch provides one avenue for nurses and health care providers to provide compassionate care. PMID- 26130466 TI - Pyrido[1,2-a]pyrimidinium ions--a novel bridgehead nitrogen heterocycles: synthesis, characterisation, and elucidation of DNA binding and cell imaging properties. AB - A novel class of bridgehead nitrogen heterocycles, pyrido[1,2-a]pyrimidinium ions, has been readily synthesized by a two-step one-pot reaction in high yields (up to 93%). These ionic compounds are bench stable and moisture tolerant and have highly fluorescent properties (quantum yield up to 0.65). A characteristic bright bluish fluorescence was observed in polar solvents such as acetonitrile and fluorescent intensity gradually diminishes with decreasing the polarity of the medium, which becomes almost negligible in toluene. These compounds also show interesting bioactivity. DNA interaction, imaging, and viability experiments with human leukemic Jurkat and KG-1A cells revealed that they are potential candidates for cancer diagnosis. PMID- 26130465 TI - Measuring Self-Care in Persons With Type 2 Diabetes: A Systematic Review. AB - This systematic review examines the characteristics and psychometric properties of the instruments used to assess self-care behaviors among persons with type 2 diabetes. Electronic databases were searched for relevant studies published in English within the past 20 years. Thirty different instruments were identified in 75 articles: 18 original instruments on type 2 diabetes mellitus self-care, 8 translated or revised version, and 4 not specific but relevant to diabetes. Twenty-one instruments were multidimensional and addressed multiple dimensions of self-care behavior. Nine were unidimensional: three focusing exclusively on medication taking, three on diet, one on physical activity, one on self monitoring of blood glucose, and one on oral care. Most instruments (22 of 30) were developed during the last decade. Only 10 were repeated more than once. Nineteen of the 30 instruments reported both reliability and validity information but with varying degrees of rigor. In conclusion, most instruments used to measure self-care were relatively new and had been applied to only a limited number of studies with incomplete psychometric profiles. Rigorous psychometric testing, operational definition of self-care, and sufficient explanation of scoring need to be considered for further instrument development. PMID- 26130467 TI - Structural mapping of the ClpB ATPases of Plasmodium falciparum: Targeting protein folding and secretion for antimalarial drug design. AB - Caseinolytic chaperones and proteases (Clp) belong to the AAA+ protein superfamily and are part of the protein quality control machinery in cells. The eukaryotic parasite Plasmodium falciparum, the causative agent of malaria, has evolved an elaborate network of Clp proteins including two distinct ClpB ATPases. ClpB1 and ClpB2 are involved in different aspects of parasitic proteostasis. ClpB1 is present in the apicoplast, a parasite-specific and plastid-like organelle hosting various metabolic pathways necessary for parasite growth. ClpB2 localizes to the parasitophorous vacuole membrane where it drives protein export as core subunit of a parasite-derived protein secretion complex, the Plasmodium Translocon of Exported proteins (PTEX); this process is central to parasite virulence and survival in the human host. The functional associations of these two chaperones with parasite-specific metabolism and protein secretion make them prime drug targets. ClpB proteins function as unfoldases and disaggregases and share a common architecture consisting of four domains-a variable N-terminal domain that binds different protein substrates, followed by two highly conserved catalytic ATPase domains, and a C-terminal domain. Here, we report and compare the first crystal structures of the N terminal domains of ClpB1 and ClpB2 from Plasmodium and analyze their molecular surfaces. Solution scattering analysis of the N domain of ClpB2 shows that the average solution conformation is similar to the crystalline structure. These structures represent the first step towards the characterization of these two malarial chaperones and the reconstitution of the entire PTEX to aid structure-based design of novel anti-malarial drugs. PMID- 26130468 TI - A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study. AB - Metabolomics is a potentially powerful tool for identification of biomarkers associated with lifestyle exposures and risk of various diseases. This is the rationale of the 'meeting-in-the-middle' concept, for which an analytical framework was developed in this study. In a nested case-control study on hepatocellular carcinoma (HCC) within the European Prospective Investigation into Cancer and nutrition (EPIC), serum (1)H nuclear magnetic resonance (NMR) spectra (800 MHz) were acquired for 114 cases and 222 matched controls. Through partial least square (PLS) analysis, 21 lifestyle variables (the 'predictors', including information on diet, anthropometry and clinical characteristics) were linked to a set of 285 metabolic variables (the 'responses'). The three resulting scores were related to HCC risk by means of conditional logistic regressions. The first PLS factor was not associated with HCC risk. The second PLS metabolomic factor was positively associated with tyrosine and glucose, and was related to a significantly increased HCC risk with OR = 1.11 (95% CI: 1.02, 1.22, P = 0.02) for a 1SD change in the responses score, and a similar association was found for the corresponding lifestyle component of the factor. The third PLS lifestyle factor was associated with lifetime alcohol consumption, hepatitis and smoking, and had negative loadings on vegetables intake. Its metabolomic counterpart displayed positive loadings on ethanol, glutamate and phenylalanine. These factors were positively and statistically significantly associated with HCC risk, with 1.37 (1.05, 1.79, P = 0.02) and 1.22 (1.04, 1.44, P = 0.01), respectively. Evidence of mediation was found in both the second and third PLS factors, where the metabolomic signals mediated the relation between the lifestyle component and HCC outcome. This study devised a way to bridge lifestyle variables to HCC risk through NMR metabolomics data. This implementation of the 'meeting-in-the-middle' approach finds natural applications in settings characterised by high-dimensional data, increasingly frequent in the omics generation. PMID- 26130469 TI - Neural Abnormalities in Nonallergic Rhinitis. AB - Sensory nerve endings within the airway epithelial cells and the solitary chemoreceptor cells, synapsing with sensory nerves, respond to airborne irritants. Transient receptor potential (TRP) channels (A1 and V1 subtypes, specifically) on these nerve endings initiate local antidromic reflexes resulting in the release of neuropeptides such as substance P and calcitonin G-related peptides. These neuropeptides dilate epithelial submucosal blood vessels and may therefore increase transudation across these vessels resulting in submucosal edema, congestion, and rhinitis. Altered expression or activity of these TRP channels can therefore influence responsiveness to irritants. Besides these pathogenic mechanisms, additional mechanisms such as dysautonomia resulting in diminished sympathetic activity and comparative parasympathetic overactivity have also been suggested as a probable mechanism. Therapeutic effectiveness for this condition has been demonstrated through desensitization of TRPV1 channels with typical agonists such as capsaicin. Other agents effective in treating nonallergic rhinitis (NAR) such as azelastine have been demonstrated to exhibit TRPV1 channel activity through the modulation of Ca(2+) signaling on sensory neurons and in nasal epithelial cells. Roles of antimuscarinic agents such as tiotropium in NAR have been suggested by associations of muscarinic cholinergic receptors with TRPV1. The associations between these channels have also been suggested as mechanisms of airway hyperreactivity in asthma. The concept of the united airway disease hypothesis suggests a significant association between rhinitis and asthma. This concept is supported by the development of late-onset asthma in about 10-40 % of NAR patients who also exhibit a greater severity in their asthma. The factors and mechanisms associating NAR with nonallergic asthma are currently unknown. Nonetheless, free immunoglobulin light chains and microRNA alteration as mediators of these inflammatory conditions may play key roles in this association. PMID- 26130470 TI - Delayed Anaphylaxis Involving IgE to Galactose-alpha-1,3-galactose. AB - Hypersensitivity in the allergic setting refers to immune reactions, stimulated by soluble antigens that can be rapidly progressing and, in the case of anaphylaxis, are occasionally fatal. As the number of known exposures associated with anaphylaxis is limited, identification of novel causative agents is important in facilitating both education and other allergen-specific approaches that are crucial to long-term risk management. Within the last 10 years, several seemingly separate observations were recognized to be related, all of which resulted from the development of antibodies to a carbohydrate moiety on proteins where exposure differed from airborne allergens but which were nevertheless capable of producing anaphylactic and hypersensitivity reactions. Our recent work has identified these responses as being due to a novel IgE antibody directed against a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha gal). This review will present the history and biology of alpha-gal and discuss our current approach to management of the mammalian meat allergy and delayed anaphylaxis. PMID- 26130471 TI - Controlled Allergen Challenge Facilities and Their Unique Contributions to Allergic Rhinitis Research. AB - The aim of this study is to review advances in basic and clinical allergic rhinitis (AR) research over the past decade that have been conducted using controlled allergen challenge facility (CACF) models of allergen challenge. Databases, including PubMed, Medline, and Web of Science were searched for articles employing an ambient pollen exposure in a controlled facility to study AR, published between 2004 and the present date, using the terms as follows: CACF, Environmental Exposure Unit (EEU), Vienna Challenge Chamber (VCC), Fraunhofer Institute Environmental Challenge Chamber, Atlanta Allergen Exposure Unit, Biogenics Research Chamber, Allergen BioCube, Chiba and Osaka Environmental Challenge Chamber, exposure unit, challenge chamber, or environmental exposure chamber. Articles were then selected for relevance to the goals of the present review, including important contributions toward clinical and/or basic science allergy research. CACFs offer sensitive, specific, and reproducible methodology for allergen challenge. They have been employed since the 1980s and offer distinct advantages over traditional in-season multicentre trials when evaluating new treatments for AR. They have provided clinically applicable efficacy and pharmacologic information about important allergy medications, including antihistamines, decongestants, antileukotrienes, immunotherapies, and nasal steroids. CACF models have also contributed to basic science and novel/experimental therapy research. To date, no direct studies have been conducted comparing outcomes from one CACF to another. Over the past decade, CACF models have played an essential role in investigating the pathophysiology of AR and evaluating new therapies. The future opportunities for this model continue to expand. PMID- 26130472 TI - Presentation and Diagnosis of Hypersensitivity to Platinum Drugs. AB - Hypersensitivity reactions (HSRs) to platinum drugs are increasing due to their extensive use in a wide variety of malignancies and the repeated exposures in patients with increased life expectancy. Understanding the incidence of HSR to platinum drugs and associated risk factors can help with the diagnosis and may provide protection against severe HSRs. A thorough clinical history with identification of the typical and atypical symptoms, the relationship with the platin administration, and the number of previous exposures are the key to the diagnosis. An elevated serum tryptase at the time of the HSR indicates that IgE and/or mast cells/basophils were involved in the HSR. Skin testing to platinum drugs is a highly sensitive and specific diagnostic tool, which helps provide risk stratification and management recommendations. Platinum specific IgE measurement and basophil activation test (BAT) are emerging as new diagnostic tools and in combination with skin testing can help support the diagnosis and the cross-reactivity between the three most commonly used platinum drugs, namely carboplatin, cisplatin, and oxaliplatin. PMID- 26130473 TI - The Effect of Ancestry and Genetic Variation on Lung Function Predictions: What Is "Normal" Lung Function in Diverse Human Populations? AB - Lung function measures are an invaluable screening test for respiratory health and have been associated with the morbidity and mortality related to different airway disease as well as all-cause mortality. Currently, reference values for spirometric measurements are obtained using equations derived from individual ethnic or racial groups. The rapid expansion of more racially and ethnically diverse populations will challenge current race-based lung function reference equations. Recent international general population studies and ancestry-based genetic studies have found that ancestry and genetic variation are determinants of lung function and have suggested a role for genetic ancestry or gene variants in future lung function reference equations. In this review, we discuss the potential limitations of current lung function reference equations in a global society which is becoming more ethnically, racially, and, thus, genetically diverse. We also focus on how an individual's ancestral background or genetic profile could provide the basis for more accurate, personalized predictions of an individual's baseline lung function. PMID- 26130474 TI - Intratympanic Gene Delivery of Antimicrobial Molecules in Otitis Media. AB - Otitis media (OM) in children is clinically important because of its detrimental effects on the development of language and motor coordination and is the most common reason for prescription of antibiotics. A recent bacteriological change in OM pathogens such as emergence of antibiotic resistance and vaccination-mediated pathogenic shift urges us to develop a new non-antibiotic strategy. The middle ear epithelium abundantly secretes a variety of antimicrobial molecules suppressing the viability of the common OM pathogens. Recently, we have demonstrated that the adenoviral vector is able to deliver the beta-defensin 2 gene to the middle ear epithelial cells in vitro and in vivo, and adenovirus mediated overexpression of beta-defensin 2 is protective for experimental OM. There are many hurdles limiting successful clinical application of gene delivery to the respiratory epithelium of the tubotympanum; however, intratympanic gene therapy with beta-defensin 2 is a promising alternative or adjuvant strategy for the management of OM. PMID- 26130475 TI - The Role of Textiles in Dermatitis: An Update. AB - Dermatitis has important implications for individuals who are affected. It can significantly impair function and quality of life. Dermatitis is multi-factorial and often includes elements of atopic dermatitis, allergic contact dermatitis, and irritant contact dermatitis in a co-existent manner. Textiles are in contact with the human skin for extended periods of time and as a result, they are an important part of the cutaneous environment. Thus, it is not surprising that textiles play a major role in both the etiology and the treatment of various types of dermatitis. This review discusses the role of textiles in dermatitis with an emphasis on interesting and recent advances, trends, perspectives, gaps, and conflicts in the field. In addition, we mention other disease processes to be aware of as they can often mimic textile pattern dermatitis. Lastly, we provide a diagnostic approach for patients presenting with textile pattern dermatitis. PMID- 26130478 TI - Coherent intensity fluctuation model for autocorrelation imaging spectroscopy with higher harmonic generating point scatterers-a comprehensive theoretical study. AB - We present a general analytical model for the intensity fluctuation autocorrelation function for second and third harmonic generating point scatterers. Expressions are derived for a stationary laser beam and for scanning beam configurations for specific correlation methodologies. We discuss free translational diffusion in both three and two dimensions. At low particle concentrations, the expressions for fluorescence are retrieved, while at high particle concentrations a rescaling of the function parameters is required for a stationary illumination beam, provided that the phase shift per unit length of the beam equals zero. PMID- 26130476 TI - Regulation of IgE Responses by gammadelta T Cells. AB - Immunoglobulin E (IgE) antibodies play a crucial role in host defense against parasite infections. However, inappropriate IgE responses are also involved in the pathogenesis of allergic diseases. The generation of IgE antibodies is a tightly controlled process regulated by multiple transcription factors, cytokines, and immune cells including gammadelta T cells. Accumulating evidence demonstrates that gammadelta T cells play a critical role in regulating IgE responses; however, both IgE-enhancing and IgE-suppressive effects are suggested for these cells in different experimental systems. In this review, we examine the available evidence and discuss the role of gammadelta T cells in IgE regulation both in the context of antigen-induced immune responses and in the state of partial immunodeficiency. PMID- 26130477 TI - Spag6 Negatively Regulates Neuronal Migration During Mouse Brain Development. AB - Sperm-associated antigen 6 (Spag6) is a Chlamydomonas reinhardtii PF16 homologous gene detected in the human testis and is crucial for sperm motility. Neuronal migration is a dynamic process requiring coordinated cytoskeletal remodeling, and Spag6 is co-localized with microtubules in Chinese hamster ovary cells and COS-1 cells. However, the role of Spag6 in neuronal migration remains unclear. Here, we demonstrated that Spag6 was continuously expressed in the developing cerebral cortex. Using in utero electroporation (IUE), we found that overexpression of Spag6 delayed the rate of neuronal migration, rather than affecting the ultimate fate of cortical neurons. Furthermore, overexpression of Spag6 caused a significant decrease in neurite number and length of cortical neurons. Our results indicated that Spag6 controlled neuronal migration as well as neurite branching and elongation. PMID- 26130479 TI - Improvement in early diagnosis of Japanese spotted fever by using a novel Rick PCR system. AB - Rickettsia diseases, including Japanese spotted fever (JSF), are serious infections. Delayed diagnosis occasionally results in life-threatening liver disorders and disseminated intravascular coagulation (DIC). Because of the shortness of the latent period, serological diagnosis is not preferable for early diagnosis of JSF. Until now, a polymerase chain reaction (PCR)-based diagnosis method has been used for early diagnosis, and the sensitivity reaches as high as 90% using skin biopsy samples as we previously reported. On the other hand, the sensitivity of the same PCR method using blood samples is limited at less than 50%. In the present study, using peripheral blood samples, we developed a novel diagnostic method for JSF using a Rick PCR system with original PCR primers, showing improved sensitivity compared with the conventional nested PCR. It may constitute a preferable diagnostic tool for early and sensitive diagnosis of Rickettsia infection. PMID- 26130481 TI - Acquiring Things: Strange Cases of Compulsive Hoarding. AB - Why has compulsive hoarding recently captured the American imagination? To what extent is hoarding a subtype of OCD or a discrete "disorder" in its own right? Can a cultural-studies and philosophical assessment of hoarding complement the medical model that has recently been offered by clinicians and the DSM IV? This essay tracks these and related questions in order to offer a theory of compulsive hoarding that pays particular attention to the sometimes distorted representation of hoarding in literature and the mainstream media. PMID- 26130480 TI - Invisible woman? AB - The number of invited women speakers at scientific meetings is much less than their proportion in a field. This means that women have fewer venues to present their research, less opportunity to increase their professional network, and smaller chances of promotion and financial support. The paucity of women speakers also sends a message to aspiring young female researchers that there is no room for them at the top. So how can we help? PMID- 26130482 TI - Meiotic chromosome configurations in triploid progeny from reciprocal crosses between wild-type diploid and natural tetraploid loach Misgurnus anguillicaudatus in China. AB - Here, we showed meiotic chromosome configurations prepared from oocyte germinal vesicles and spermatocytes of triploid loaches produced from reciprocal crosses between wild-type diploids (2n = 50) obtained from Dalian, Liaoning Province, China and natural tetraploids (4n = 100) from Chibi, Hubei Province, China. Major meiotic cells in triploids comprised 25 bivalents and 25 univalents, but cells with one to five trivalents were also observed. When three homologous chromosomes bearing nucleolar organizing regions (NOR) were identified with the detection of signals or positive sites by silver staining, chromomycin A3 staining and fluorescence in situ hybridization with a 5.8S + 28S rDNA probe, two third of selected triploid cells gave a configuration including one bivalent with two NORs (association of two homologous chromosomes) and one univalent with one NOR. However, other triploid cells showed three univalent each of which had one NOR, suggesting a failure of synapsis between homologous chromosomes. These results suggested that triploid female and male should produce aneuploid gametes with the theoretical mode at 1.5n (37 or 38 chromosomes). PMID- 26130483 TI - Shared language, diverging genetic histories: high-resolution analysis of Y chromosome variability in Calabrian and Sicilian Arbereshe. AB - The relationship between genetic and linguistic diversification in human populations has been often explored to interpret some specific issues in human history. The Albanian-speaking minorities of Sicily and Southern Italy (Arbereshe) constitute an important portion of the ethnolinguistic variability of Italy. Their linguistic isolation from neighboring Italian populations and their documented migration history, make such minorities particularly effective for investigating the interplay between cultural, geographic and historical factors. Nevertheless, the extent of Arbereshe genetic relationships with the Balkan homeland and the Italian recipient populations has been only partially investigated. In the present study we address the genetic history of Arbereshe people by combining highly resolved analyses of Y-chromosome lineages and extensive computer simulations. A large set of slow- and fast-evolving molecular markers was typed in different Arbereshe communities from Sicily and Southern Italy (Calabria), as well as in both the putative Balkan source and Italian sink populations. Our results revealed that the considered Arbereshe groups, despite speaking closely related languages and sharing common cultural features, actually experienced diverging genetic histories. The estimated proportions of genetic admixture confirm the tight relationship of Calabrian Arbereshe with modern Albanian populations, in accordance with linguistic hypotheses. On the other hand, population stratification and/or an increased permeability of linguistic and geographic barriers may be hypothesized for Sicilian groups, to account for their partial similarity with Greek populations and their higher levels of local admixture. These processes ultimately resulted in the differential acquisition or preservation of specific paternal lineages by the present-day Arbereshe communities. PMID- 26130484 TI - Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma. AB - Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing. Analysis of 83 known A/M factors identified pathogenic/likely pathogenic variants in PAX6, OTX2 and NDP in three patients. A novel heterozygous likely pathogenic variant in PAX6, c.767T>C, p.(Val256Ala), was identified in two brothers with bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea and congenital glaucoma; the unaffected mother appears to be a mosaic carrier. While A/M has been reported as a rare feature, this is the first report of congenital primary aphakia in association with PAX6 and the identified allele represents the first variant in the PAX6 homeodomain to be associated with A/M. A novel pathogenic variant in OTX2, c.651delC, p.(Thr218Hisfs*76), in a patient with syndromic bilateral anophthalmia and a hemizygous pathogenic variant in NDP, c.293 C>T, p.(Pro98Leu), in two brothers with isolated bilateral microphthalmia and sclerocornea were also identified. Pathogenic/likely pathogenic variants were not discovered in the 25 remaining A/M cases. This study underscores the utility of whole-exome sequencing for identification of causative mutations in highly variable ocular phenotypes as well as the extreme genetic heterogeneity of A/M conditions. PMID- 26130485 TI - Mucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes. AB - Homozygous mutations in GNPTAB and GNPTG are classically associated with mucolipidosis II (ML II) alpha/beta and mucolipidosis III (ML III) alpha/beta/gamma, which are rare lysosomal storage disorders characterized by multiple pathologies. Recently, variants in GNPTAB, GNPTG, and the functionally related NAGPA gene have been associated with non-syndromic persistent stuttering. In a worldwide sample of 1013 unrelated individuals with non-syndromic persistent stuttering we found 164 individuals who carried a rare non-synonymous coding variant in one of these three genes. We compared the frequency of these variants with those in population-matched controls and genomic databases, and their location with those reported in mucolipidosis. Stuttering subjects displayed an excess of non-synonymous coding variants compared to controls and individuals in the 1000 Genomes and Exome Sequencing Project databases. We identified a total of 81 different variants in our stuttering cases. Virtually all of these were missense substitutions, only one of which has been previously reported in mucolipidosis, a disease frequently associated with complete loss-of-function mutations. We hypothesize that rare non-synonymous coding variants in GNPTAB, GNPTG, and NAGPA may account for as much as 16% of persistent stuttering cases, and that variants in GNPTAB and GNPTG are at different sites and may in general, cause less severe effects on protein function than those in ML II alpha/beta and ML III alpha/beta/gamma. PMID- 26130486 TI - Outcomes of a randomised controlled trial of a complex genetic counselling intervention to improve family communication. AB - When an inherited genetic condition is diagnosed in an individual it has implications for other family members. Privacy legislation and ethical considerations can restrict health professionals from communicating directly with other family members, and so it is frequently the responsibility of the first person in a family to receive the diagnosis (the proband) to share this news. Communication of genetic information is challenging and many at-risk family members remain unaware of important information that may be relevant to their or their children's health. We conducted a randomised controlled trial in six public hospitals to assess whether a specifically designed telephone counselling intervention improved family communication about a new genetic diagnosis. Ninety five probands/parents of probands were recruited from genetics clinics and randomised to the intervention or control group. The primary outcome measure was the difference between the proportion of at-risk relatives who contacted genetics services for information and/or genetic testing. Audit of the family genetic file after 18 months revealed that 25.6% of intervention group relatives compared with 20.9% of control group relatives made contact with genetic services (adjusted odds ratio (OR) 1.30, 95% confidence interval 0.70-2.42, P=0.40). Although no major difference was detected overall between the intervention and control groups, there was more contact in the intervention group where the genetic condition conferred a high risk to offspring (adjusted OR 24.0, 95% confidence interval 3.4-168.5, P=0.001). The increasing sophistication and scope of genetic testing makes it imperative for health professionals to consider additional ways of supporting families in communicating genetic information. PMID- 26130487 TI - Embryonic stem cell patents at European top court. PMID- 26130489 TI - Treatment of acute stroke: an update. AB - Stroke is the second leading cause of global mortality after coronary heart disease, and a major cause of neurological disability. About 17 million strokes occur worldwide each year. Patients with stroke often require long-term rehabilitation following the acute phase, with ongoing support from the community and nursing home care. Thus, stroke is a devastating disease and a major economic burden on society. In this overview, we discuss current strategies for specific treatment of stroke in the acute phase, focusing on intravenous thrombolysis and mechanical thrombectomy. We will consider two important issues related to intravenous thrombolysis treatments: (i) how to shorten the delay between stroke onset and treatment and (ii) how to reduce the risk of symptomatic intracerebral haemorrhage. Intravenous thrombolysis has been approved treatment for acute ischaemic stroke in most countries for more than 10 years, with rapid development towards new treatment strategies during that time. Mechanical thrombectomy using a new generation of endovascular tools, stent retrievers, is found to improve functional outcome in combination with pharmacological thrombolysis when indicated. There is an urgent need to increase public awareness of how to recognize a stroke and seek immediate attention from the healthcare system, as well as shorten delays in prehospital and within-hospital settings. PMID- 26130488 TI - Evaluation of transethnic fine mapping with population-specific and cosmopolitan imputation reference panels in diverse Asian populations. AB - There has been limited success in identifying causal variants underlying association signals observed in genome-wide association studies (GWAS). The use of 1000 Genomes Project (1KGP) allows the imputation to estimate the genetic information at untyped variants. However, long stretches of high linkage disequilibrium within the genome prevent us from differentiating between causal variants and perfect surrogates, thus limiting our ability to identify causal variants. Transethnic strategies have been proposed as a possible solution to mitigate this. However, these studies generally rely on imputing genotypes from multiple ancestries from 1KGP but not against population-specific reference panels. Here, we perform the first transethnic fine-mapping study across three Asian cohorts from diverse ancestries at the loci implicated with eye and blood lipid traits, using population-specific reference panels that have been generated by whole-genome sequencing samples from the same ancestry groups. Our study outlines several challenges faced in a fine-mapping exercise where one simply aims to meta-analyse existing GWAS that have been imputed against reference haplotypes from the 1KGP. PMID- 26130490 TI - Tip-enhanced Raman scattering--Targeting structure-specific surface characterization for biomedical samples. AB - Tip-enhanced Raman scattering (TERS) has become a powerful tool for nanoscale structural analysis for several branches of organic, inorganic, and biological chemistry. This highly sensitive technique enables molecular characterization with a lateral resolution far beyond Abbe's diffraction limit and correlates structural and topographic information on a nanometer scale. In this review, the current experimental concepts with respect to their strengths and obstacles are introduced and discussed. A further focus was set to biochemistry comprising applications like nucleic acids, proteins, and microorganisms, thus demonstrating the potential use towards the pharmaceutically relevant challenges where nanometer resolution is required. PMID- 26130491 TI - Electric-field-induced strong enhancement of electroluminescence in multilayer molybdenum disulfide. AB - The layered transition metal dichalcogenides have attracted considerable interest for their unique electronic and optical properties. While the monolayer MoS2 exhibits a direct bandgap, the multilayer MoS2 is an indirect bandgap semiconductor and generally optically inactive. Here we report electric-field induced strong electroluminescence in multilayer MoS2. We show that GaN-Al2O3 MoS2 and GaN-Al2O3-MoS2-Al2O3-graphene vertical heterojunctions can be created with excellent rectification behaviour. Electroluminescence studies demonstrate prominent direct bandgap excitonic emission in multilayer MoS2 over the entire vertical junction area. Importantly, the electroluminescence efficiency observed in multilayer MoS2 is comparable to or higher than that in monolayers. This strong electroluminescence can be attributed to electric-field-induced carrier redistribution from the lowest energy points (indirect bandgap) to higher energy points (direct bandgap) in k-space. The electric-field-induced electroluminescence is general for other layered materials including WSe2 and can open up a new pathway towards transition metal dichalcogenide-based optoelectronic devices. PMID- 26130492 TI - Effects of fucoidan on insulin stimulation and pancreatic protection via the cAMP signaling pathway in vivo and in vitro. AB - Diabetes is a global disease, in which pancreatic dysfunction is an important pathological process. In previous years, interest in the biological activities of seaweed has increased. Fucoidan is an extract of the seaweed Fucus vesiculosus, which has been widely investigated. The present study aimed to determine the effects of fucoidan on insulin stimulation and pancreatic protection in vivo and in vitro. Goto-Kakizaki (GK) rats were provided with free access to standard food, with or without fucoidan, for 13 weeks, following which the body weights, and blood glucose and serum insulin levels of the rats were measured. Wistar rats were used as a control. In addition, the RIN-5F rat insulin-secreting cell line was treated with fucoidan in high glucose conditions, following which the dose dependent and time-dependent effects of fucoidan were determined, and the concentration of insulin was measured. Glybenclamide was used as a positive control. In vivo, the body weight and serum insulin levels decreased, whereas blood glucose levels increased significantly in the GK rats, compared with the Wistar control rats. Although, fucoidan did not improve changes in body weight, the increased blood glucose levels were reduced and the decreased serum insulin levels were increased in the GK rats following oral administration of fucoidan. In vitro, fucoidan did not exhibit significant cytotoxicity towards the RIN-5F cells, and the insulin secretion increased significantly in a dose- and time dependent manner. Treatment with amylin, an islet amyloid polypeptide and glybenclamide inhibitor, did not inhibit the stimulatory activity of fucoidan. The results of the present study also demonstrated that the concentration of cyclic adenosine monophosphate (cAMP) was significantly increased in the fucoidan treated RIN-5F cells, and this increase was dose- and time-dependent. In addition, treatment with a phosphodiesterase inhibitor, which decreases the degradation of cAMP, significantly increased fucoidan-induced insulin secretion, whereas treatment with an adenylyl cyclase inhibitor, which decreases the generation of cAMP, significantly decreased fucoidan-induced insulin secretion. In conclusion, these data indicated that fucoidan may stimulate insulin secretion and provide pancreatic protection via the cAMP signaling pathway, in vivo and in vitro. PMID- 26130493 TI - Response to letter by Hoaglin: Heterogeneity in likelihood ratios. PMID- 26130494 TI - False discovery rate control is not always a replacement for Bonferroni adjustment (Letter commenting on: J Clin Epidemiol. 2014;67:850-7). PMID- 26130495 TI - Data from a nationwide registry on sports-related sudden cardiac deaths in Germany. AB - BACKGROUND: Prospective national registries examining the incidence and aetiology of sports-related sudden cardiac death (SrSCD) not only in competitive athletes but also in recreational sports participants are uncommon. In May 2012, a prospective registry on SrSCD was installed to examine the incidence and particularly the aetiology of such events in the general population in Germany. METHODS: The registry consists of a web-based platform to record SrSCD cases. Media-monitoring and cooperation with 15 institutes of forensic medicine complemented the search. SrSCD was defined as death occurring during sports activity or up to 1 hour after its cessation, regardless of successful resuscitation. We included subjects at all levels of competition as well as recreational athletes. RESULTS: After 30 months of observation, 144 SrSCDs were recorded (mean age 46.8 +/- 16.2 years). The overall incidence was 1.2 1.5/million/year, with 97% being male. Most of the cases occurred in the context of non-elite competitive or recreational sports. Football and running were the most common disciplines. In subjects <=35 years, myocarditis prevailed, whereas in athletes >=35 years, CAD predominated by far. Few cardiomyopathies were observed. CONCLUSIONS: In Germany, the largest proportion of SrSCDs occurs in middle-aged men during recreational sports or non-elite competitive sports. The distribution of cardiac diseases responsible for SrSCD seems to vary among European countries. Our findings may indicate the need for a larger focus on myocarditis prevention in the young as well as widening the screening scope to younger athletes below the 'elite' level and to senior athletes. PMID- 26130496 TI - Relationship between recurrent miscarriage and early preterm delivery and recurrent events in patients with manifest vascular disease: The SMART study. AB - BACKGROUND: Women with a complication of pregnancy are at increased risk of cardiovascular morbidity and mortality later in life. Yet, information on risk of recurrent events in women with a previous cardiovascular event is lacking. We aimed to assess the relationship between early preterm delivery, (recurrent) miscarriage and the risk for recurrent cardiovascular events in women with manifest vascular disease. METHODS: We included 1014 women with a mean age of 60 years from the SMART study, a prospective ongoing cohort study among subjects with clinically manifest vascular disease. The included women had a history of >=1 pregnancy and were followed for the occurrence of subsequent vascular events. The relationship between the pregnancy complications ((miscarriage (gestational age <14 weeks), recurrent miscarriage (>=3 miscarriages) and early preterm delivery (gestational age 14-32 weeks)) and cardiovascular morbidity and mortality were estimated using multivariable adjusted hazard ratios. RESULTS: During a mean follow-up of 5.0 years, 80 women had a recurrent cardiovascular event, of which 28 were fatal. A history of recurrent miscarriage was associated with an increased risk for a recurrent cardiovascular event (hazard ratio 4.3 95% confidence interval 1.7--10.9). In addition, early preterm delivery was related to a 4.1 (95% confidence interval 1.5--11.3) fold increased risk of cardiovascular death in women with previous cardiovascular disease. No statistically significant relationships were found for less than three miscarriages. CONCLUSIONS: In women with previous cardiovascular disease, an obstetric history of recurrent miscarriage is associated with an increased risk of recurrent cardiovascular morbidity and early preterm delivery with cardiovascular mortality. PMID- 26130497 TI - Psychometric properties of the Cancer and Treatment Distress (CTXD) measure in hematopoietic cell transplantation patients. AB - BACKGROUND: This study examines the psychometric properties of a measure of distress specific to cancer and its treatment, as tested in patients receiving hematopoietic cell transplantation (HCT). METHODS: With multicenter enrollment, the Cancer and Treatment Distress (CTXD) measure was administered to adults beginning HCT as part of an assessment that included the Center for Epidemiologic Studies Depression (CESD), Profile of Mood States, and Medical Outcomes Study Short Form 36 (SF-36). RESULTS: From eight transplant centers, 176 of 219 eligible patients completed the assessment. Average age was 46.7 years (SD = 11.9), 59% were male, and the majority were identified as Caucasian (93%). Principal components analysis with the CTXD identified 22 items that loaded onto six factors explaining 69% of the variance: uncertainty, health burden, identity, medical demands, finances, and family strain. Internal consistency reliability for the 22 items was 0.91. The receiver operating characteristic area under the curve was 0.85 (95% CI [0.79, 0.91]), with a cut point of 1.1 resulting in a sensitivity rate of 0.91 and a specificity rate of 0.58. Convergent validity and divergent validity were confirmed with large correlations of the CTXD total score with the CESD, Profile of Mood States, and SF-36 mental health; and a smaller correlation with the SF-36 physical function (r = -0.30). CONCLUSIONS: The CTXD is a reliable and valid measure of distress for HCT recipients and captures nearly all cases of depression on the CESD in addition to detecting distress in those who are not depressed. It has potential value as both a research and clinical screening measure for distress. PMID- 26130498 TI - Extracorporeal membrane oxygenation for the treatment of adult sickle cell acute chest syndrome. AB - Sickle cell disease (SCD) is a hereditary haemoglobinopathy that results in polymerization of haemoglobin molecules and subsequent vaso-occlusion. A common cause of death in adults is acute chest syndrome (AChS) with resulting hypoxemic respiratory failure.Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used successfully in acutely reversible respiratory failure when conventional mechanical ventilation has been unable to adequately oxygenate and ventilate in a lung-protective fashion.We present an adult SCD patient with severe respiratory failure due to AChS, successfully treated with VV-ECMO. We also discuss some of the technical challenges and considerations when using ECMO in the SCD patient. PMID- 26130499 TI - Organic-Inorganic Hybrid Materials Based on Basket-like {Ca?P6Mo18O73} Cages. AB - Four basket-like organic-inorganic hybrids, formulated as [{Cu(II)(H2O)2}{Ca4(H2O)4(HO0.5)3(en)2}{Ca?P6Mo4(V)Mo14(VI)O73}].7H2O (1), (H4bth)[{Fe(II)(H2O)}{Ca?P6Mo18(VI)O73}].4H2O (2), (H2bih)3[{Cu(II)(H2O)2}{Ca?P6Mo2(V)Mo16(VI)O73}].2H2O (3), (H2bib)3[{Fe(II)(H2O)2}{Ca?P6Mo2(V) Mo16(VI)O73}].4H2O (4), (bth = 1,6 bis(triazole)hexane; bih = 1,6-bis(imidazol)hexane; bib = 1,4 bis(imidazole)butane) have been hydrothermally synthesized and fully characterized. Compounds 1-4 contain polyoxoanion [Ca?P6Mon(V)Mo18 n(VI)O73]((6+n)-) (n = 0, 2, or 4) (abbreviated as {P6Mo18O73}) as a basic building block, which is composed of a "basket body" {P2Mo14} unit and a "handle" liked {P4Mo4} fragment encasing an alkaline-earth metal Ca(2+) cation in the cage. Compound 1 exhibits an infrequent 2D layer structure linked by the Cu(H2O)2 linker and an uncommon tetranuclear calcium complex, while compound 2 is 8 connected 2-D layers connected by binuclear {Fe2(H2O)3} segaments, which are observed for the first time as 2-D basket-like assemblies. Compounds 3 and 4 are similar 1D Z-typed chains bonded by M(H2O)2 units (M = Cu for 3 and Fe for 4). The optical band gaps of 1-4 reveal their semiconductive natures. They exhibit universal highly efficient degradation ability for typical dyes such as methylene blue, methyl orange, and rhodamine B under UV light. The lifetime and catalysis mechanism of the catalysts have been investigated. The compounds also show good bifunctional electrocatalytic behavior for oxidation of amino acids and reduction of NO2(-). PMID- 26130501 TI - Problematic Internet Use and Its Correlates Among Students from Three Medical Schools Across Three Countries. AB - OBJECTIVE: The authors aimed to assess and compare problematic internet use among medical students enrolled in a graduate degree course in one school each from Croatia, India, and Nigeria and to assess correlates of problematic use among these students. METHODS: The questionnaire included a sociodemographic profile of participants and Young's Internet Addiction Test. RESULTS: The final analysis included 842 subjects. Overall, 38.7 and 10.5 % of respondents scored in the mild and moderate categories. Only a small fraction (0.5 %) of students scored in the severe category. Being male and spending more time on the internet were correlated with problematic internet use. Moreover, a significantly higher proportion of participants who scored above the cutoff used the Internet for browsing, social networking, chatting, gaming, shopping, and viewing pornography. However, there was no difference between the two groups with regard to using the internet for e-mailing or academic activities. CONCLUSIONS: It is important to address problematic internet use among medical students. The correlates can help identify those at increased risk. PMID- 26130502 TI - No Survival Benefit for Patients with Treatment in Certified Breast Centers-A Population-based Evaluation of German Cancer Registry Data. AB - Much time and money has been spent on the establishment and preservation of certified breast centers (CBCs), but up to now there is almost no evidence for whether certification results in an improved outcome for breast cancer patients. The aim of this evaluation was to assess, whether the certification of specialized units had any influence on their patients' outcomes and if a survival difference between CBC patients and non-CBC patients can be shown. This population-based analysis included cancer registry data from 32,789 operated breast cancer patients with no prior cancer diagnosis and with active follow-up. They were diagnosed between 2004 and 2010 in four different regions in Germany. Survival was investigated using the Kaplan-Meier method and multivariate Cox regression analysis. A survival difference was found neither between patients with treatment before and after certification of specialized units nor between CBC patients and non-CBC patients aged up to 75 years. Only for patients older than 75 years, an improved survival could be seen for CBC patients (adjusted hazard ratio 0.77; 95% confidence interval 0.68-0.87). The improved survival of elderly CBC patients is most likely caused by selection effects concerning health status differences and not by processes attributable to certification. Thus, this study found that as of yet, certification has not influenced survival of breast cancer patients. PMID- 26130504 TI - Limited efficacy of antimicrobial metaphylaxis in finishing pigs: A randomized clinical trial. AB - Pigs that die from pathogens associated with porcine respiratory disease complex (PRDC) in the late finishing period represent a significant economic wastage. While it is common to apply antimicrobial metaphylaxis (AM) to control PRDC, there are few studies exploring the potential cost-saving benefits of AM. In this study we examined the value of using AM in commercially reared, late finishing pigs, from farms with endemic PRDC. A total of 732 pigs from four AIAO wean to market sources, were blocked into 2 matching cohorts, based on enrollment body weight, sex, and rectal temperature. The cohorts received either control (C) or AM (Tulathromycin 2.5mg/kg IM, Zoetis, Florham Park, NJ, USA). Post treatment weight gain over the 21 day period was used as a measure of health and productivity. The AM treated pigs in the lowest weight quartile at enrollment, showed a significantly improved weight gain over controls (18.5 kg vs. 16.4 kg, mean difference=2.1 kg, CI 1.10-3.10, p=0.005) that was not evident in any other starting weight quartiles. These results indicate that the biological advantage and associated improvement in growth efficiency associated with the use of AM against PRDC, is only conferred to a specific sub-set of animals. The economic advantage of this strategy is therefore, only likely if the indicators of potential benefit (e.g., lighter weight cohort) can be reliably established. Further studies are needed to determine whether targeted AM could be effectively applied across the industry. PMID- 26130503 TI - The B subunit of Escherichia coli heat-labile toxin alters the development and antigen-presenting capacity of dendritic cells. AB - Escherichia coli's heat-labile enterotoxin (Etx) and its non-toxic B subunit (EtxB) have been characterized as adjuvants capable of enhancing T cell responses to co-administered antigen. Here, we investigate the direct effect of intravenously administered EtxB on the size of the dendritic and myeloid cell populations in spleen. EtxB treatment appears to enhance the development and turnover of dendritic and myeloid cells from precursors within the spleen. EtxB treatment also gives a dendritic cell (DC) population with higher viability and lower activation status based on the reduced expression of MHC-II, CD80 and CD86. In this respect, the in vivo effect of EtxB differs from that of the highly inflammatory mediator lipopolysaccharide. In in vitro bone marrow cultures, EtxB treatment was also found to enhance the development of DC from precursors dependent on Flt3L. In terms of the in vivo effect of EtxB on CD4 and CD8 T cell responses in mice, the interaction of EtxB directly with DC was demonstrated following conditional depletion of CD11c(+) DC. In summary, all results are consistent with EtxB displaying adjuvant ability by enhancing the turnover of DC in spleen, leading to newly mature myeloid and DC in spleen, thereby increasing DC capacity to perform as antigen-presenting cells on encounter with T cells. PMID- 26130505 TI - Deer response to exclusion from stored cattle feed in Michigan, USA. AB - Disease and damage from white-tailed deer (Odocoileus virginianus) continually threaten the livelihood of agricultural producers and the economy in the United States, as well as challenge state and federal wildlife managers. Threats can be partially addressed by excluding free-ranging deer from livestock-related resources. Throughout the year, use of stored livestock feed by deer in northern Lower Michigan (MI), USA fluctuates, though their presence is relatively consistent. Since 2008, use of livestock areas and resources by deer has been reduced through intensive efforts by livestock producers in cooperation with state and federal agencies. These efforts focused on excluding deer from stored cattle feed in areas where deer were abundant. We monitored deer activity from Jan 2012 to June 2013 on 6 cattle farms in northern MI using GPS collars to evaluate behavioral effects of excluding deer from stored feed. We characterized areas deer occupied before and after installing 2361 m of fences and gates to exclude deer from stored cattle feed. Following fence installation, 9 deer previously accessing stored feed shifted to patterns of habitat use similar to 5 deer that did not use stored feed. However, continued attempts to regain access to stored feed were made at low frequencies, emphasizing the need to maintain the integrity of fences and keep gates closed for damage prevention and biosecurity. PMID- 26130506 TI - Influence of using a single facial vein as outflow in full-face transplantation: A three-dimensional computed tomographic study. AB - BACKGROUND: The aim of this study was to evaluate the contribution of a single unilateral facial vein in the venous outflow of total-face allograft using three dimensional computed tomographic imaging techniques to further elucidate the mechanisms of venous complications following total-face transplant. METHODS: Full face soft-tissue flaps were harvested from fresh adult human cadavers. A single facial vein was identified and injected distally to the submandibular gland with a radiopaque contrast (barium sulfate/gelatin mixture) in every specimen. Following vascular injections, three-dimensional computed tomographic venographies of the faces were performed. Images were viewed using TeraRecon Software (Teracon, Inc., San Mateo, CA, USA) allowing analysis of the venous anatomy and perfusion in different facial subunits by observing radiopaque filling venous patterns. RESULTS: Three-dimensional computed tomographic venographies demonstrated a venous network with different degrees of perfusion in subunits of the face in relation to the facial vein injection side: 100% of ipsilateral and contralateral forehead units, 100% of ipsilateral and 75% of contralateral periorbital units, 100% of ipsilateral and 25% of contralateral cheek units, 100% of ipsilateral and 75% of contralateral nose units, 100% of ipsilateral and 75% of contralateral upper lip units, 100% of ipsilateral and 25% of contralateral lower lip units, and 50% of ipsilateral and 25% of contralateral chin units. CONCLUSION: Venographies of the full-face grafts revealed better perfusion in the ipsilateral hemifaces from the facial vein in comparison with the contralateral hemifaces. Reduced perfusion was observed mostly in the contralateral cheek unit and contralateral lower face including the lower lip and chin units. PMID- 26130507 TI - "Hummingbird" behaviour of N-heterocyclic carbenes stabilises out-of-plane bonding of AuCl and CuCl units. AB - An N-heterocyclic carbene substituted by two expanded 9-ethyl-9-fluorenyl groups was shown to bind an AuCl unit in an unusual manner, namely with the Au?X rod sitting out of the plane defined by the heterocyclic carbene unit. As shown by X ray studies and DFT calculations, the observed large pitch angle (21 degrees ) arises from an easy displacement of the gold(I) atom away from the carbene lone pair axis, combined with the stabilisation provided by weak CH???Au interactions involving aliphatic and aromatic H atoms of the NHC wingtips. Weak, intermolecular Cl???H bonds are likely to cooperate with the H???Au interactions to stabilise the out-of-plane conformation. A general belief until now was that tilt angles in NHC complexes arise mainly from steric effects within the first coordination sphere. PMID- 26130509 TI - The search for the origin of factor VIII synthesis and its impact on therapeutic strategies for hemophilia A. PMID- 26130510 TI - Dangerous liaisons: cooperation between Pbx3, Meis1 and Hoxa9 in leukemia. PMID- 26130511 TI - Rituximab maintenance therapy in diffuse large B-cell lymphoma: is XY the most important variable? PMID- 26130512 TI - Personalized medicine in adult acute lymphoblastic leukemia. PMID- 26130508 TI - Nrf2 and Nrf2-related proteins in development and developmental toxicity: Insights from studies in zebrafish (Danio rerio). AB - Oxidative stress is an important mechanism of chemical toxicity, contributing to developmental toxicity and teratogenesis as well as to cardiovascular and neurodegenerative diseases and diabetic embryopathy. Developing animals are especially sensitive to effects of chemicals that disrupt the balance of processes generating reactive species and oxidative stress, and those anti oxidant defenses that protect against oxidative stress. The expression and inducibility of anti-oxidant defenses through activation of NFE2-related factor 2 (Nrf2) and related proteins is an essential process affecting the susceptibility to oxidants, but the complex interactions of Nrf2 in determining embryonic response to oxidants and oxidative stress are only beginning to be understood. The zebrafish (Danio rerio) is an established model in developmental biology and now also in developmental toxicology and redox signaling. Here we review the regulation of genes involved in protection against oxidative stress in developing vertebrates, with a focus on Nrf2 and related cap'n'collar (CNC)-basic-leucine zipper (bZIP) transcription factors. Vertebrate animals including zebrafish share Nfe2, Nrf1, Nrf2, and Nrf3 as well as a core set of genes that respond to oxidative stress, contributing to the value of zebrafish as a model system with which to investigate the mechanisms involved in regulation of redox signaling and the response to oxidative stress during embryolarval development. Moreover, studies in zebrafish have revealed nrf and keap1 gene duplications that provide an opportunity to dissect multiple functions of vertebrate NRF genes, including multiple sensing mechanisms involved in chemical-specific effects. PMID- 26130513 TI - Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT. AB - Acute myeloid leukemia is the most common indication for an allogeneic hematopoietic cell transplant. The introduction of reduced intensity conditioning has expanded the recipient pool for transplantation, which has importantly made transplant an option for the more commonly affected older age groups. Reduced intensity conditioning allogeneic transplantation is currently the standard of care for patients with intermediate or high-risk acute myeloid leukemia and is now most often employed in older patients and those with medical comorbidities. Despite being curative for a significant proportion of patients, post-transplant relapse remains a challenge in the reduced intensity conditioning setting. Herein we discuss the studies that demonstrate the feasibility of reduced intensity conditioning allogeneic transplants, compare the outcomes of reduced intensity conditioning versus chemotherapy and conventional myeloablative conditioning regimens, describe the optimal donor and stem cell source, and consider the impact of post-remission consolidation, comorbidities, center experience, and more intensive (reduced toxicity conditioning) regimens on outcomes. Additionally, we discuss the need for further prospective studies to optimize transplant outcomes. PMID- 26130515 TI - FAMILIAL PATTERNS OF HOARDING SYMPTOMS. AB - BACKGROUND: Previous research suggests that hoarding aggregates in families and is associated with health and safety risks and family problems. The present study examined gender- and diagnosis-related differences in reports of hoarding symptoms among first-degree relatives of people who hoard, and of clinical and community samples. METHODS: The present study included 443 participants in a study of hoarding behavior: 217 with hoarding disorder (HD), 96 with obsessive compulsive disorder (OCD), and 130 nonclinical community controls (CC). Assessment included a detailed interview of familial patterns of hoarding behaviors among parents and siblings and measures of hoarding severity. RESULTS: In the combined sample, participants reported more hoarding among female (mothers, sisters) than male (fathers, brothers) relatives. Significantly more female than male participants indicated they had a parent or any first-degree relative with hoarding behaviors. However, within the HD sample no significant gender effects were found for household, safety, and functioning variables, or for hoarding symptom severity. In an age- and gender-matched subsample (total n = 150), HD participants reported more hallmark hoarding symptoms (difficulty discarding and saving/clutter), and acquiring among their relatives compared to OCD and CC samples, and parents had higher rates than siblings. CONCLUSIONS: Hoarding symptoms appear to be common among first-degree relatives of people who hoard and are also found among relatives of control samples. The predominance of hoarding symptoms among female relatives may indicate genetic or modeling transmission but this requires further study using large twin samples. Clinicians should consider that family members may also have significant hoarding symptoms. PMID- 26130514 TI - Efficacy of an Fc-modified anti-CD123 antibody (CSL362) combined with chemotherapy in xenograft models of acute myelogenous leukemia in immunodeficient mice. AB - The prognosis of older patients with acute myelogenous leukemia is generally poor. The interleukin-3 receptor alpha-chain (CD123) is highly expressed on the surface of acute leukemia cells compared with normal hematopoietic stem cells. CSL362 is a fully humanized, CD123-neutralizing monoclonal antibody containing a modified Fc structure, which enhances human natural killer cell antibody dependent cell-mediated cytotoxicity. Six continuous acute myelogenous leukemia xenografts established from patient explants and characterized by cell and molecular criteria, produced progressively lethal disease 42-202 days after transplantation. CSL362 alone reduced engraftment of one of four and three of four acute myelogenous leukemia xenografts in the bone marrow and peripheral organs, respectively. A cytarabine and daunorubicin regimen was optimized using this model to identify potentially synergistic interactions with CSL362. Cytarabine/daunorubicin improved the survival of mice engrafted with four of four acute myelogenous leukemia xenografts by 31-41 days. Moreover, CSL362 extended the survival of cytarabine/daunorubicin-treated mice for two of two acute myelogenous leukemia xenografts, while augmentation of natural killer cell deficient NSG mice with adoptively transferred human natural killer cells improved survival against a single xenograft. Interestingly, this enhanced CSL362 efficacy was lost in the absence of chemotherapy. This study shows that acute myelogenous leukemia xenografts provide a platform for the evaluation of new therapeutics, simulating complex in vivo interactions, and that the in vivo efficacy of CSL362 supports continued clinical development of this drug. PMID- 26130516 TI - Quantitative analysis of differential protein expression in cervical carcinoma cells after zeylenone treatment by stable isotope labeling with amino acids in cell culture. AB - Cervical carcinoma is a malignant tumor that poses a serious threat to women's health and survival. Approximately 10-25% of cervical cancers are adenocarcinomas (ACs). AC has high rates of recurrence and mortality, while there is no effective treatment for now. Zeylenone (Zey), which is isolated from an ethanol extract of the leaves of Uvaria grandiflora Roxb. of the family Annonaceae, has shown potent inhibitory activity against various tumor cells, including cervical carcinoma cells. To gain insight into the molecular mechanism underlying the effect of Zey on AC, we quantified protein expression changes in AC cells treated with Zey. We used stable isotope labeling with amino acids in cell culture (SILAC) in combination with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and bioinformatics analysis to compare protein expression profiles in HeLa cells before and after Zey treatment. Of 1805 differentially expressed proteins identified, 229 were screened as key protein molecules and classified into nine categories. Profiling of differentially expressed proteins contributed to our understanding of the molecular mechanism by which Zey induces HeLa cell apoptosis. Using this method, candidate targets can be identified for developing new drugs against cervical carcinoma. PMID- 26130517 TI - Sub-inhibitory concentrations of penicillin G induce biofilm formation by field isolates of Actinobacillus pleuropneumoniae. AB - Actinobacillus pleuropneumoniae is a Gram-negative bacterium and causative agent of porcine pleuropneumonia. This is a highly contagious disease that causes important economic losses to the swine industry worldwide. Penicillins are extensively used in swine production and these antibiotics are associated with high systemic clearance and low oral bioavailability. This may expose A. pleuropneumoniae to sub-inhibitory concentrations of penicillin G when the antibiotic is administered orally. Our goal was to evaluate the effect of sub minimum inhibitory concentration (MIC) of penicillin G on the biofilm formation of A. pleuropneumoniae. Biofilm production of 13 field isolates from serotypes 1, 5a, 7 and 15 was tested in the presence of sub-MIC of penicillin G using a polystyrene microtiter plate assay. Using microscopy techniques and enzymatic digestion, biofilm architecture and composition were also characterized after exposure to sub-MIC of penicillin G. Sub-MIC of penicillin G significantly induced biofilm formation of nine isolates. The penicillin G-induced biofilms contained more poly-N-acetyl-D-glucosamine (PGA), extracellular DNA and proteins when compared to control biofilms grown without penicillin G. Additionally, penicillin G-induced biofilms were sensitive to DNase which was not observed with the untreated controls. Furthermore, sub-MIC of penicillin G up-regulated the expression of pgaA, which encodes a protein involved in PGA synthesis, and the genes encoding the envelope-stress sensing two-component regulatory system CpxRA. In conclusion, sub-MICs of penicillin G significantly induce biofilm formation and this is likely the result of a cell envelope stress sensed by the CpxRA system resulting in an increased production of PGA and other matrix components. PMID- 26130518 TI - Isolation of a novel thermophilic Campylobacter from cases of spotty liver disease in laying hens and experimental reproduction of infection and microscopic pathology. AB - The condition known as spotty liver disease or spotty liver syndrome can cause significant mortality in free range laying hen flocks. It has been described in Europe and Australia but the aetiology has not been established. There are similarities between spotty liver disease and avian vibrionic hepatitis, a condition which was reported in the 1950s. A Vibrio-like organism was suspected to be the cause of avian vibrionic hepatitis, although this organism was never fully characterised. We report the isolation of a novel Campylobacter from five separate outbreaks of spotty liver disease. The conditions required for culture, the growth characteristics, electron microscopical morphology and results of the phenotypic tests used in the identification of this novel Campylobacter sp. are described. The novel Campylobacter is slow growing and fastidious and does not grow on media routinely used for isolating Campylobacter sp. The morphology is typical for a Campylobacter sp. and phenotypic tests and a duplex real time PCR test differentiate the novel Campylobacter from other members of the genus. 16S rRNA analysis of 19 isolates showed an identical sequence which appears to represent a hitherto unknown sub lineage within the genus Campylobacter. Experimental intraperitoneal infection of four week old SPF chickens produced microscopic liver pathology indistinguishable from natural disease and the novel Campylobacter was recovered from the experimentally infected chicks. The isolates described appear to be a possible causal organism for spotty liver disease. PMID- 26130519 TI - Fantastic plastic? Experimental evaluation of polyurethane bone substitutes as proxies for human bone in trauma simulations. AB - Recent years have seen steady improvements in the recognition and interpretation of violence related injuries in human skeletal remains. Such work has at times benefited from the involvement of biological anthropologists in forensic casework and has often relied upon comparison of documented examples with trauma observed in skeletal remains. In cases where no such example exists investigators must turn to experimentation. The selection of experimental samples is problematic as animal proxies may be too dissimilar to humans and human cadavers may be undesirable for a raft of reasons. The current article examines a third alternative in the form of polyurethane plates and spheres marketed as viable proxies for human bone in ballistic experiments. Through subjecting these samples to a range of impacts from both modern and archaic missile weapons it was established that such material generally responds similarly to bone on a broad, macroscopic scale but when examined in closer detail exhibits a range of dissimilarities that call for caution in extrapolating such results to real bone. PMID- 26130521 TI - Microplate fluorescence protease assays test the inhibition of select North American snake venoms' activities with an anti-proteinase library. AB - Snake envenomation is a relatively neglected significant world health problem, designated an orphan disease by the WHO. While often effective, antivenins are insufficient. Could another approach greatly aid inhibition of the venom toxins? New fluorescent substrates for measuring protease activity in microplate assays suitable for high throughput screening were tested and found reproducible with snake venom. Representative North American venoms showed relatively strong proteinase and collagenase, but weaker elastase activities. Caseinolytic activity is inhibited by the nonspecific proteinase inhibitor 1,10-phenanthroline and by EDTA, as is collagenase activity, consistent with the action of metalloproteinases. Both general protease and collagenase assays CV average 3%, and Km measured were above normal working conditions. Using a library of anti proteinase compounds with multiple venoms revealed high inhibitor activity by three agents with known multiple metalloproteinase inhibitor activity (Actinonin, GM6001, and NNGH), which incidentally supports the concept that much of the degradative activity of certain venoms is due to metalloproteinases with collagenase activity. These results together support the use of microplate proteinase assays, particularly this collagenase assay, in future drug repurposing studies leading to the development of new treatments for those envenomations that have a major proteolytic component in their pathophysiology. PMID- 26130520 TI - Trends in hospital deaths among human immunodeficiency virus-infected patients during the antiretroviral therapy era, 1995 to 2011. AB - OBJECTIVE: Mortality in hospitalized human immunodeficiency virus (HIV)-infected patients is not well described. We sought to characterize in-hospital deaths among HIV-infected patients in the antiretroviral (ART) era and identify factors associated with mortality. METHODS: We reviewed the medical records of hospitalized HIV-infected patients who died from January 1, 1995 to December 31, 2011 at an urban teaching hospital. We evaluated trends in early and late ART use and deaths due to acquired immunodeficiency syndrome (AIDS) and non-AIDS, and identified clinical and demographic correlates of non-AIDS deaths. RESULTS: In hospital deaths declined significantly from 1995 to 2011 (P < 0.0001); those attributable to non-AIDS increased (43% to 70.5%, P < 0.0001). Non-AIDS deaths were most commonly caused by non-AIDS infection (20.3%), cardiovascular (11.3%) and liver disease (8.5%), and non-AIDS malignancy (7.8%). Patients with non-AIDS compared to AIDS-related deaths were older (median age 48 vs 40 years, P < 0.0001), more likely to be on ART (74.1% vs 55.8%, P = 0.0001), less likely to have a CD4 count of <200 cells/mm(3) (47.2% vs 97.1%, P < 0.0001), and more likely to have an HIV viral load of <=400 copies/mL (38.1% vs 4.1%, P < 0.0001). Non-AIDS deaths were associated with 4.5 and 4.2 times greater likelihood of comorbid underlying liver and cardiovascular disease, respectively. CONCLUSIONS: Non-AIDS deaths increased significantly during the ART era and are now the most common cause of in-hospital deaths; non-AIDS infection, cardiovascular and liver disease, and malignancies were major contributors to mortality. Higher CD4 cell count, liver, and cardiovascular comorbidities were most strongly associated with non-AIDS deaths. Interventions targeting non-AIDS-associated conditions are needed to reduce inpatient mortality among HIV-infected patients. PMID- 26130522 TI - In vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1 5. AB - To date, over 40 subtypes of botulinum neurotoxins (BoNTs) have been identified. BoNTs are classified into 7 serotypes distinguished primarily by their antigenic properties, but also characterized by their unique SNARE targets and cleavage sites, host specificity, and duration of action. Sequencing efforts in the last decade have identified several subtypes within the serotypes. Subtypes are currently defined as distinct based solely on amino acid sequence comparison, with a similarity cut-off of 2.5% difference. Ten subtypes have been identified for BoNT/A, which is the serotype associated with the most severe human botulism and also the most commonly used serotype for clinical purposes. Analyses of several of these subtypes have revealed distinct characteristics, ranging from differences in cell entry and enzyme kinetics to differences in potency in mice and cell-model specific potency. A long-term activity study in cultured primary neurons has indicated that BoNT/A1, 2, 4, and 5 have a similar duration of action, whereas BoNT/A3 has a significantly shorter duration of action. This report describes an in vivo mouse study, showing that after local injection BoNT/A2 resulted in faster onset of local paralysis than BoNT/A1, 3, 4, and 5, whereas BoNT/A3 resulted in significantly faster recovery of motor-neuron deficiency. PMID- 26130523 TI - The thioredoxin reductase--Thioredoxin redox system cleaves the interchain disulphide bond of botulinum neurotoxins on the cytosolic surface of synaptic vesicles. AB - Botulinum neurotoxins (BoNTs) are Janus toxins, as they are at the same time the most deadly substances known and one of the safest drugs used in human therapy. They specifically block neurotransmission at peripheral nerves through the proteolysis of SNARE proteins, i.e. the essential proteins which are the core of the neuroexocytosis machinery. Even if BoNTs are traditionally known as seven main serotypes, their actual number is much higher as each serotype exists in many different subtypes, with individual biological properties and little antigenic relations. Since BoNTs can be used as biological weapons, and the only currently available therapy is based on immunological approaches, the existence of so many different subtypes is a major safety problem. Nevertheless, all BoNT isoforms are structurally similar and intoxicate peripheral nerve endings via a conserved mechanism. They consist of two chains linked by a unique disulphide bond which must be reduced to enable their toxicity. We found that thioredoxin 1 and its reductase compose the cell redox system responsible for this reduction, and its inhibition via specific chemicals significantly reduces BoNTs activity, in vitro as well as in vivo. Such molecules can be considered as lead compounds for the development of pan-inhibitors. PMID- 26130524 TI - Carriage of Clostridium perfringens by benthic crabs in a sewage-polluted estuary. AB - The Estuary of Bahia Blanca (EBB), Argentina, is an important wetland under intense sewage pollution. We investigated the occurrence of Clostridium perfringens (CP) in populations of two benthic crabs (Neohelice granulata and Cyrtograpsus angulatus) and in sediment from the EBB. CP was found in 49.1% of the crabs and all of the isolates were identified as type A. The alpha (cpa) and enterotoxin (cpe) encoding genes were identified. Genetic analyses identified 13 novel sequence types, and found no clustering among isolates, suggesting that CP is not part of the crabs' commensal flora. CP carriage was 51 times more likely in crabs from the area nearest sewage outfalls compared with crabs from a reference site. Our in vitro experiments suggest that the carriage of CP in crabs is transient. The use of these benthic crabs as monitoring organisms of sewage pollution in coastal habitats is proposed. PMID- 26130525 TI - Emerging contaminants (pharmaceuticals, personal care products, a food additive and pesticides) in waters of Sydney estuary, Australia. AB - The current investigation of marine water from 30 sites adjacent to stormwater outlets across the entire Sydney estuary is the first such research in Australia. The number of analytes detected were: 8/59 pharmaceutical compounds (codeine, paracetamol, tramadol, venlafaxine, propranolol, fluoxetine, iopromide and carbamazepine), 7/38 of the pesticides (2,4-dichlorophenoxyacetic acid (2,4-D), 3,4-dichloroaniline, carbaryl, diuron, 2-methyl-4-chlorophenoxyacetic acid (MCPA), mecoprop and simazine) and 0/3 of the personal care products (PCPs) analysed. An artificial sweetener (acesulfame) was detected, however none of the nine antibiotics analysed were identified. Sewage water is not discharged to this estuary, except infrequently as overflow during high-precipitation events. The presence of acesulfame (a recognised marker of domestic wastewater) and pharmaceuticals in water from all parts of the estuary after a dry period, suggests sewage water is leaking into the stormwater system in this catchment. The pesticides are applied to the environment and were discharged via stormwater to the estuary. PMID- 26130526 TI - Concentration distribution and potential health risk of heavy metals in Mactra veneriformis from Bohai Bay, China. AB - To investigate the pollution level and evaluate the potential health risks of heavy metals, the concentrations of chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), antimony (Sb), and lead (Pb) were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in 198 clams (Mactra veneriformis) collected from 11 sites of the Bohai Bay. The results showed that heavy metal concentrations in the clams were different at different sites (p<0.05). Mn was dominant with a percentage of 22.08-77.03% in heavy metals, followed by Zn with 12.66-57.11%, and the concentration of Pb was the lowest with 0.45-1.04%. The potential health risk to consumers was evaluated by the target hazard quotient (THQ) and the maximum daily consumption rate (CRmax). The results indicated that the THQs of Co were the highest with the values of 1.125, 1.665, and 1.144 at three sections; the values of other individual metals were <1, which indicated that consumption of clams from the study areas caused health risks due to Co. Moreover, the CRmax values also indicated the potential health risk caused by Co in clams consumed in this area. Pearson correlation analysis and principal component analysis (PCA) indicated that there were significantly positive or negative correlations between the heavy metals (p<0.05), and the studied metals were divided into four groups. The results indicated that the concentrations of heavy metals in clams were affected not only by pollution sources but also by the characteristics of clams that could absorb selectively and accumulate special metals. This study offers important information on the pollution levels of heavy metals in clams and warns consumers of the health risks associated with the consumption of clams in the area. PMID- 26130527 TI - Mercury concentrations in feathers of marine birds in Arctic Canada. AB - Mercury (Hg) concentrations are a concern in the Canadian Arctic, because they are relatively high compared to background levels and to similar species farther south, and are increasing in many wildlife species. Among marine birds breeding in the Canadian Arctic, Hg concentrations have been monitored regularly in eggs and intermittently in livers, but feathers have generally not been used as an indicator of Hg exposure or burden. We examined Hg concentrations in six marine bird species in the Canadian Arctic. Ivory gull Pagophila eburnea, feather Hg was exceptionally high, while glaucous gull Larus hyperboreus feather Hg was unexpectedly low, and ratios of feather THg to egg THg varied across species. The proportion of total Hg that was comprised of methyl Hg in ivory gull feathers was lower than in other species, and may be related to photo-demethylation or keratin breakdown in semi-opaque feather tissue. PMID- 26130528 TI - Where the sun never shines. PMID- 26130529 TI - Our international colleagues. PMID- 26130530 TI - [Re: Different guidelines for treatment of prostate cancer]. PMID- 26130531 TI - [Re: Diffusion-weighted MR in transient ischemic attacks]. PMID- 26130532 TI - [C.E. Kvistad replies]. PMID- 26130533 TI - [Re: Diffusion-weighted MR in transient ischemic attacks]. PMID- 26130534 TI - [Re: An announcement of concern about antibiotics in chicken feed]. PMID- 26130535 TI - [T. Midtvedt replies]. PMID- 26130538 TI - [Lack of academic requirements for air ambulance service]. PMID- 26130539 TI - [Vaccination--trust or coercion?]. PMID- 26130540 TI - [How do we compare quality of health care?]. PMID- 26130541 TI - [Interdisciplinary education for better pain treatment]. PMID- 26130542 TI - [Prospective multicenter study--art of the possible?]. PMID- 26130545 TI - International medical graduates' perceptions of entering the profession in Norway. AB - BACKGROUND: There is little knowledge available about how it feels for an international medical graduate arriving in Norway. We have investigated how the initial period as an employee of the Norwegian health services is perceived. MATERIAL AND METHOD: We conducted semi-structured interviews with 16 international medical graduates who had foreign training and citizenship. They had worked as doctors in Norway for less than two years. Transcriptions of the interviews were analysed using the Systematic Text Condensation method. RESULTS: Their background for working in Norway varied. Some had an affiliation to the country and a social network, which appeared to be a support during the initial period. Many perceived the authorisation process as bureaucratic and as throwing suspicion on them. The doctors felt that they could cope with most of their work assignments, but reported having faced challenges in terms of language, a lack of insight into systems and uncertainty regarding what was expected of the doctor's role in a Norwegian context. There was also uncertainty associated with a perceived absence of collegial support. Because of the availability of jobs, some had adjusted their career plans towards psychiatry, geriatrics or general practice. INTERPRETATION: It appears that preparatory measures such as training courses, tests and the authorisation process fail to provide the practice-related experience and local knowledge that many doctors feel that they need in their new job situation. Measures such as language training and introduction to systems would be likely to improve their general well-being as well as integration. PMID- 26130546 TI - Foreign doctors in Norwegian psychiatry - is there a need for a mentoring scheme? AB - BACKGROUND: In line with other Western countries, the number of foreign doctors in Norway has greatly increased in recent years. Inadequate language skills and cultural differences may give rise to challenges. The objective of this study was to investigate the views of Norwegian specialty registrars in psychiatry with regard to a mentoring scheme for foreign doctors and how such a support scheme ought to be designed. MATERIAL AND METHOD: Data were collected in focus-group interviews with specialty registrars in psychiatry. Altogether 24 Norwegian and 16 foreign doctors participated in a total of five focus groups. Thematic analysis was used as methodology. RESULTS: One consistent finding pertained to the differing views on the need for a mentoring scheme among the Norwegian and foreign doctors respectively. The foreign doctors perceived few problems in terms of language and culture, while their Norwegian colleagues had occasionally experienced considerable problems in this respect. Moreover, obstacles in terms of attitude to a mentoring scheme were revealed among the foreign doctors, as well as differing opinions regarding the organisation of such a scheme, especially in terms of its voluntariness and having peers as mentors (horizontal organisation) versus having superiors as mentors (vertical organisation). INTERPRETATION: The differences in attitude to a mentoring scheme are partly caused by perception of the problem's extent and partly by varying norms and values among foreign and Norwegian doctors respectively. We propose that various forms of mentoring scheme be tested in a pilot project, in which the foreign doctors are actively involved. PMID- 26130547 TI - Examination and treatment of scaphoid fractures and pseudarthrosis. AB - BACKGROUND: About 2,000 patients annually incur a fractured scaphoid in Norway. Assessment and diagnosis can be difficult, and fractures are overlooked. Scaphoid fractures have traditionally been cast-immobilised, but for the last decade screw fixing has been used increasingly, and offers hope of a higher healing frequency and improved function. Some scaphoid fractures are not diagnosed in the acute phase and some do not heal after treatment. Patients may then end up with painful pseudarthrosis. The purpose of this article is to provide an overview of the assessment, treatment and outcomes of scaphoid fractures. METHOD: The article is based on literature searches in PubMed and the authors' own clinical experience. RESULTS: Primary diagnosis of scaphoid fractures and subsequent plaster cast immobilisation yield very good clinical results. Surgery should be limited to displaced fractures, fractures forming part of more extensive wrist injuries and exceptional other cases. Results comparable a quality equivalent to cast immobilisation are achieved by experienced surgeons in this area. Untreated scaphoid fractures often result in painful pseudarthrosis with subsequent abnormal position of the carpal bones and secondary arthrosis. This outcome can be counteracted by surgery on old fractures with bone grafting, internal fixation and cast immobilisation. INTERPRETATION: Norwegian procedures for treating scaphoid fractures/pseudarthrosis are consistent with internationally documented good practice. Assessment of wrist pain following falls can be improved by conducting clinical tests for scaphoid fracture and radiology with four wrist projections. In the event of clinical suspicion, but no X-ray findings, the patient should be referred for a CT or MRI scan. PMID- 26130548 TI - [Emergency thoracotomy]. PMID- 26130549 TI - Adolescent with respiratory impairments and short-lived fever. PMID- 26130550 TI - An extraordinary tale of an ordinary case. PMID- 26130551 TI - [Mary Lyon and the hypothesis on X-chromosome inactivation]. PMID- 26130552 TI - The doctor's waiting room. PMID- 26130553 TI - The microbial community in our bowel - flora or fauna? PMID- 26130560 TI - [Healthy beverage]. PMID- 26130561 TI - [Fathers leave--a useful experience!]. PMID- 26130565 TI - Combination of selenium-enriched green tea polysaccharides and Huo-ji polysaccharides synergistically enhances antioxidant and immune activity in mice. AB - BACKGROUND: The aim of this study was to investigate the influence of a combination of selenium-enriched green tea polysaccharides (Se-GTP) and Huo-ji polysaccharides (HJP) on the immune function and antioxidant activity in mice. RESULTS: The results showed that the indices of spleen and thymus were markedly increased, and the activity of natural killer (NK) cell was promoted in mice treated with the combination of Se-GTP and HJP. The combined treatment of Se-GTP and HJP also reduced the content of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in splenocytes. In addition, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were remarkably enhanced, and malondialdehyde (MDA) levels were significantly reduced in mice treated with combination of Se-GTP and HJP. Furthermore, the combined treatment of Se-GTP and HJP increased nuclear factor erythroid 2-related factor (Nrf2) expression at mRNA and protein levels in splenocytes. The effects of the combination treatment of Se GTP and HJP in mice were stronger than with Se-GTP or HJP treatment alone. CONCLUSION: Our study suggests that the combined administration of Se-GTP and HJP can synergistically improve immune function and decrease the oxidative stress by enhancing the mechanisms involved in the clearance of free radicals. PMID- 26130566 TI - Half of US cardiovascular deaths are due to modifiable risk factors, study finds. PMID- 26130567 TI - Optimization of experimental conditions for functional in vitro characterization of humanized antibodies specific for staphylococcal enterotoxin B. AB - Staphylococcus aureus is a common nosocomial infection and its resistance to penicillin and methicillin antibiotics is a growing clinical problem. We previously described the development of a humanized anti-Staphylococcus enterotoxin B (SEB) antibody derived from the mouse antibody made by the 20B1 hybridoma. This antibody was humanized and characterized kinetically by surface plasmon resonance demonstrating that the humanized clones retained binding to SEB. Clones were then functionally characterized in an in vitro assay demonstrating that the murine 20B1, chimeric and humanized antibodies potently inhibited SEB-induced murine splenocyte proliferation assay. Here, we describe a human cell-based screening assay, optimized by varying multiple experimental parameters that resulted in an assay that was used to demonstrate full and potent neutralization by the parental, chimeric and humanized antibodies. The replacement of fetal bovine serum (FBS) with normal human serum (NHS) was found to be a crucial factor in the performance of the human cell based screening assay that enabled the calculation of mAb efficacy and potency. In addition, we found that anti-SEB antibodies showed similar efficacy and potency with a triple mutant Fc region (designed to be effector function null) or a wild-type Fc region, which is in contrast to previously described studies. PMID- 26130568 TI - A Bioinspired Molecular Polyoxometalate Catalyst with Two Cobalt(II) Oxide Cores for Photocatalytic Water Oxidation. AB - To overcome the bottleneck of water splitting, the exploration of efficient, selective, and stable water oxidation catalysts (WOCs) is crucial. We report an all-inorganic, oxidatively and hydrolytically stable WOC based on a polyoxometalate [(A-alpha-SiW9 O34)2Co8(OH)6(H2O)2(CO3)3](16-) (Co8 POM). As a cobalt(II)-based cubane water oxidation catalyst, Co8POM embeds double Co(II)4O3 cores. The self-assembled catalyst is similar to the oxygen evolving complex (OEC) of photosystem II (PS II). Using [Ru(bpy)3](2+) as a photosensitizer and persulfate as a sacrificial electron acceptor, Co8POM exhibits excellent water oxidation activity with a turnover number (TON) of 1436, currently the highest among bioinspired catalysts with a cubical core, and a high initial turnover frequency (TOF). Investigation by several spectroscopy, spectrometry, and other techniques confirm that Co8POM is a stable and efficient catalyst for visible light-driven water oxidation. The results offer a useful insight into the design of water oxidation catalysts. PMID- 26130570 TI - Forming Stereogenic Centers in Acyclic Systems from Alkynes. AB - The combined carbometalation/zinc homologation followed by reactions with alpha heterosubstituted aldehydes and imines proceed through a chair-like transition structure with the substituent of the incoming aldehyde residue preferentially occupying a pseudo-axial position to avoid the two gauche interactions. The heteroatom in the axial position produces a chelated intermediate (and not a Cornforth-Evans transition structure for alpha-chloro aldehydes and imines) leading to a face differentiation in the allylation reaction. This method provides access to functionalized products in which three new carbon-carbon bonds and two to three stereogenic centers, including a quaternary one, were created in acyclic systems in a single-pot operation from simple alkynes. PMID- 26130569 TI - The role of miR-100 in regulating apoptosis of breast cancer cells. AB - Breast cancer is a serious health problem worldwide. Inhibition of apoptosis plays a major role in breast cancer tumorigenesis. MicroRNAs (miRNAs) play crucial roles in the regulation of apoptosis. However, the regulation of breast cancer apoptosis by miRNAs has not been intensively investigated. To address this issue, the effect of miR-100 on the cell proliferation of different breast cancer cells was characterized in the present study. The results showed that miR-100 was significantly upregulated in SK-BR-3 cells compared with other human breast cancer cells (MCF7, MDA-MB-453, T47D, HCC1954 and SUM149). Silencing miR-100 expression with anti-miRNA-100 oligonucleotide (AMO-miR-100) initiated apoptosis of SK-BR-3 cells in vitro and in vivo. However, the overexpression of miR-100 led to the proliferation inhibition of the miR-100-downregulated breast cancer cells. Antagonism of miR-100 in SK-BR-3 cells increased the expression of MTMR3, a target gene of miR-100, which resulted in the activation of p27 and eventually led to G2/M cell-cycle arrest and apoptosis. The downregulation of miR-100 sensitized SK-BR-3 cells to chemotherapy. Therefore, our finding highlights a novel aspect of the miR-100-MTMR3-p27 pathway in the molecular etiology of breast cancer. PMID- 26130571 TI - Long-duration animal tracking in difficult lighting conditions. AB - High-throughput analysis of animal behavior requires software to analyze videos. Such software typically depends on the experiments' being performed in good lighting conditions, but this ideal is difficult or impossible to achieve for certain classes of experiments. Here, we describe techniques that allow long duration positional tracking in difficult lighting conditions with strong shadows or recurring "on"/"off" changes in lighting. The latter condition will likely become increasingly common, e.g., for Drosophila due to the advent of red-shifted channel rhodopsins. The techniques enabled tracking with good accuracy in three types of experiments with difficult lighting conditions in our lab. Our technique handling shadows relies on single-animal tracking and on shadows' and flies' being accurately distinguishable by distance to the center of the arena (or a similar geometric rule); the other techniques should be broadly applicable. We implemented the techniques as extensions of the widely-used tracking software Ctrax; however, they are relatively simple, not specific to Drosophila, and could be added to other trackers as well. PMID- 26130572 TI - Dynamic stability during level walking and obstacle crossing in persons with facioscapulohumeral muscular dystrophy. AB - Patients with FSHD suffer from progressive skeletal muscle weakness, which is associated with an elevated fall risk. To obtain insight into fall mechanisms in this patient group, we aimed to assess dynamic stability during level walking and obstacle crossing in patients at different disease stages. Ten patients with at least some lower extremity weakness were included, of whom six were classified as moderately affected and four as mildly affected. Ten healthy controls were also included. Level walking at comfortable speed was assessed, as well as crossing a 10 cm high wooden obstacle. We assessed forward and lateral dynamic stability, as well as spatiotemporal and kinematics variables. During level walking, the moderately affected group demonstrated a lower walking speed, which was accompanied by longer step times and smaller step lengths, yet dynamic stability was unaffected. When crossing the obstacle, however, the moderately affected patients demonstrated reduced forward stability margins during the trailing step, which was accompanied by an increased toe clearance and greater trunk and hip flexion. This suggests that during level walking, the patients effectively utilized compensatory strategies for maintaining dynamic stability, but that the moderately affected group lacked the capacity to fully compensate for the greater stability demands imposed by obstacle crossing, rendering them unable to maintain optimal stability levels. The present results highlight the difficulties that FSHD patients experience in performing this common activity of daily living and may help explain their propensity to fall in the forward direction. PMID- 26130573 TI - Inference of Markovian properties of molecular sequences from NGS data and applications to comparative genomics. AB - MOTIVATION: Next-generation sequencing (NGS) technologies generate large amounts of short read data for many different organisms. The fact that NGS reads are generally short makes it challenging to assemble the reads and reconstruct the original genome sequence. For clustering genomes using such NGS data, word-count based alignment-free sequence comparison is a promising approach, but for this approach, the underlying expected word counts are essential.A plausible model for this underlying distribution of word counts is given through modeling the DNA sequence as a Markov chain (MC). For single long sequences, efficient statistics are available to estimate the order of MCs and the transition probability matrix for the sequences. As NGS data do not provide a single long sequence, inference methods on Markovian properties of sequences based on single long sequences cannot be directly used for NGS short read data. RESULTS: Here we derive a normal approximation for such word counts. We also show that the traditional Chi-square statistic has an approximate gamma distribution ,: using the Lander-Waterman model for physical mapping. We propose several methods to estimate the order of the MC based on NGS reads and evaluate those using simulations. We illustrate the applications of our results by clustering genomic sequences of several vertebrate and tree species based on NGS reads using alignment-free sequence dissimilarity measures. We find that the estimated order of the MC has a considerable effect on the clustering results ,: and that the clustering results that use a N: MC of the estimated order give a plausible clustering of the species. AVAILABILITY AND IMPLEMENTATION: Our implementation of the statistics developed here is available as R package 'NGS.MC' at http://www-rcf.usc.edu/~fsun/Programs/NGS-MC/NGS-MC.html CONTACT: fsun@usc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26130574 TI - ProFET: Feature engineering captures high-level protein functions. AB - MOTIVATION: The amount of sequenced genomes and proteins is growing at an unprecedented pace. Unfortunately, manual curation and functional knowledge lag behind. Homologous inference often fails at labeling proteins with diverse functions and broad classes. Thus, identifying high-level protein functionality remains challenging. We hypothesize that a universal feature engineering approach can yield classification of high-level functions and unified properties when combined with machine learning approaches, without requiring external databases or alignment. RESULTS: In this study, we present a novel bioinformatics toolkit called ProFET (Protein Feature Engineering Toolkit). ProFET extracts hundreds of features covering the elementary biophysical and sequence derived attributes. Most features capture statistically informative patterns. In addition, different representations of sequences and the amino acids alphabet provide a compact, compressed set of features. The results from ProFET were incorporated in data analysis pipelines, implemented in python and adapted for multi-genome scale analysis. ProFET was applied on 17 established and novel protein benchmark datasets involving classification for a variety of binary and multi-class tasks. The results show state of the art performance. The extracted features' show excellent biological interpretability. The success of ProFET applies to a wide range of high-level functions such as subcellular localization, structural classes and proteins with unique functional properties (e.g. neuropeptide precursors, thermophilic and nucleic acid binding). ProFET allows easy, universal discovery of new target proteins, as well as understanding the features underlying different high-level protein functions. AVAILABILITY AND IMPLEMENTATION: ProFET source code and the datasets used are freely available at https://github.com/ddofer/ProFET. CONTACT: michall@cc.huji.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26130575 TI - GDFuzz3D: a method for protein 3D structure reconstruction from contact maps, based on a non-Euclidean distance function. AB - MOTIVATION: To date, only a few distinct successful approaches have been introduced to reconstruct a protein 3D structure from a map of contacts between its amino acid residues (a 2D contact map). Current algorithms can infer structures from information-rich contact maps that contain a limited fraction of erroneous predictions. However, it is difficult to reconstruct 3D structures from predicted contact maps that usually contain a high fraction of false contacts. RESULTS: We describe a new, multi-step protocol that predicts protein 3D structures from the predicted contact maps. The method is based on a novel distance function acting on a fuzzy residue proximity graph, which predicts a 2D distance map from a 2D predicted contact map. The application of a Multi Dimensional Scaling algorithm transforms that predicted 2D distance map into a coarse 3D model, which is further refined by typical modeling programs into an all-atom representation. We tested our approach on contact maps predicted de novo by MULTICOM, the top contact map predictor according to CASP10. We show that our method outperforms FT-COMAR, the state-of-the-art method for 3D structure reconstruction from 2D maps. For all predicted 2D contact maps of relatively low sensitivity (60-84%), GDFuzz3D generates more accurate 3D models, with the average improvement of 4.87 A in terms of RMSD. AVAILABILITY AND IMPLEMENTATION: GDFuzz3D server and standalone version are freely available at http://iimcb.genesilico.pl/gdserver/GDFuzz3D/. CONTACT: iamb@genesilico.pl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26130576 TI - Estimating beta diversity for under-sampled communities using the variably weighted Odum dissimilarity index and OTUshuff. AB - MOTIVATION: In profiling the composition and structure of complex microbial communities via high throughput amplicon sequencing, a very low proportion of community members are typically sampled. As a result of this incomplete sampling, estimates of dissimilarity between communities are often inflated, an issue we term pseudo beta-diversity. RESULTS: We present a set of tools to identify and correct for the presence of pseudo beta-diversity in contrasts between microbial communities. The variably weighted Odum dissimilarity (DwOdum) allows for down weighting the influence of either abundant or rare taxa in calculating a measure of similarity between two communities. We show that down-weighting the influence of rare taxa can be used to minimize pseudo beta-diversity arising from incomplete sampling. Down-weighting the influence of abundant taxa can increase the sensitivity of hypothesis testing. OTUshuff is an associated test for identifying the presence of pseudo beta-diversity in pairwise community contrasts. AVAILABILITY AND IMPLEMENTATION: A Perl script for calculating the DwOdum score from a taxon abundance table and performing pairwise contrasts with OTUshuff can be obtained at http://www.ars.usda.gov/services/software/software.htm?modecode=30-12-10-00. CONTACT: daniel.manter@ars.usda.gov SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26130577 TI - A DNA shape-based regulatory score improves position-weight matrix-based recognition of transcription factor binding sites. AB - MOTIVATION: The position-weight matrix (PWM) is a useful representation of a transcription factor binding site (TFBS) sequence pattern because the PWM can be estimated from a small number of representative TFBS sequences. However, because the PWM probability model assumes independence between individual nucleotide positions, the PWMs for some TFs poorly discriminate binding sites from non binding-sites that have similar sequence content. Since the local three dimensional DNA structure ('shape') is a determinant of TF binding specificity and since DNA shape has a significant sequence-dependence, we combined DNA shape derived features into a TF-generalized regulatory score and tested whether the score could improve PWM-based discrimination of TFBS from non-binding-sites. RESULTS: We compared a traditional PWM model to a model that combines the PWM with a DNA shape feature-based regulatory potential score, for accuracy in detecting binding sites for 75 vertebrate transcription factors. The PWM+shape model was more accurate than the PWM-only model, for 45% of TFs tested, with no significant loss of accuracy for the remaining TFs. AVAILABILITY AND IMPLEMENTATION: The shape-based model is available as an open-source R package at that is archived on the GitHub software repository at https://github.com/ramseylab/regshape/. CONTACT: stephen.ramsey@oregonstate.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26130578 TI - Integrating full spectrum of sequence features into predicting functional microRNA-mRNA interactions. AB - MOTIVATION: MicroRNAs (miRNAs) play important roles in general biological processes and diseases pathogenesis. Identifying miRNA target genes is an essential step to fully understand the regulatory effects of miRNAs. Many computational methods based on the sequence complementary rules and the miRNA and mRNA expression profiles have been developed for this purpose. It is noted that there have been many sequence features of miRNA targets available, including the context features of the target sites, the thermodynamic stability and the accessibility energy for miRNA-mRNA interaction. However, most of current computational methods that combine sequence and expression information do not effectively integrate full spectrum of these features; instead, they perceive putative miRNA-mRNA interactions from sequence-based prediction as equally meaningful. Therefore, these sequence features have not been fully utilized for improving miRNA target prediction. RESULTS: We propose a novel regularized regression approach that is based on the adaptive Lasso procedure for detecting functional miRNA-mRNA interactions. Our method fully takes into account the gene sequence features and the miRNA and mRNA expression profiles. Given a set of sequence features for each putative miRNA-mRNA interaction and their expression values, our model quantifies the down-regulation effect of each miRNA on its targets while simultaneously estimating the contribution of each sequence feature to predicting functional miRNA-mRNA interactions. By applying our model to the expression datasets from two cancer studies, we have demonstrated our prediction results have achieved better sensitivity and specificity and are more biologically meaningful compared with those based on other methods. AVAILABILITY AND IMPLEMENTATION: The source code is available at: http://nba.uth.tmc.edu/homepage/liu/miRNALasso. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: Yin.Liu@uth.tmc.edu. PMID- 26130579 TI - Biomechanical Comparison of External Fixation and Compression Screws for Transverse Tarsal Joint Arthrodesis. AB - BACKGROUND: Transverse tarsal joint arthrodesis is commonly performed in the operative treatment of hindfoot arthritis and acquired flatfoot deformity. While fixation is typically achieved using screws, failure to obtain and maintain joint compression sometimes occurs, potentially leading to nonunion. External fixation is an alternate method of achieving arthrodesis site compression and has the advantage of allowing postoperative compression adjustment when necessary. However, its performance relative to standard screw fixation has not been quantified in this application. We hypothesized that external fixation could provide transverse tarsal joint compression exceeding that possible with screw fixation. METHODS: Transverse tarsal joint fixation was performed sequentially, first with a circular external fixator and then with compression screws, on 9 fresh-frozen cadaveric legs. The external fixator was attached in abutting rings fixed to the tibia and the hindfoot and a third anterior ring parallel to the hindfoot ring using transverse wires and half-pins in the tibial diaphysis, calcaneus, and metatarsals. Screw fixation comprised two 4.3 mm headless compression screws traversing the talonavicular joint and 1 across the calcaneocuboid joint. Compressive forces generated during incremental fixator foot ring displacement to 20 mm and incremental screw tightening were measured using a custom-fabricated instrumented miniature external fixator spanning the transverse tarsal joint. RESULTS: The maximum compressive force generated by the external fixator averaged 186% of that produced by the screws (range, 104%-391%). Fixator compression surpassed that obtainable with screws at 12 mm of ring displacement and decreased when the tibial ring was detached. No correlation was found between bone density and the compressive force achievable by either fusion method. CONCLUSION: The compression across the transverse tarsal joint that can be obtained with a circular external fixator including a tibial ring exceeds that which can be obtained with 3 headless compression screws. Screw and external fixator performance did not correlate with bone mineral density. This study supports the use of external fixation as an alternative method of generating compression to help stimulate fusion across the transverse tarsal joints. CLINICAL RELEVANCE: The findings provide biomechanical evidence to support the use of external fixation as a viable option in transverse tarsal joint fusion cases in which screw fixation has failed or is anticipated to be inadequate due to suboptimal bone quality. PMID- 26130580 TI - Epidemiology and Microbiology of Sepsis Syndromes in a University-Affiliated Urban Teaching Hospital and Level-1 Trauma and Burn Center. AB - PURPOSE: To use the 2010 to 2011 data collected by structured chart review to provide a detailed up-to-date description of the epidemiology and microbiology of the sepsis syndromes. METHODS: Prospective observational study conducted at a university-affiliated urban teaching hospital and level-1 trauma and burn center. All adult patients who triggered a Code Sepsis in the emergency department (ED) between January 2010 and December 2011 were included. RESULTS: One hundred eighty four patients presented with a verified sepsis syndrome and triggered a Code Sepsis in the ED during the studied time period. The mean hospital and intensive care unit length of stays (LOSs) were 15.4 (interquartile range [IQR] = 14) and 6.7 (IQR = 5) days, respectively. The total inpatient mortality was 19% (n = 35). Patients with an unspecified source of infection and those without an isolated pathogen had the highest inpatient mortality, 42.1% (n = 8) and 23.3% (n = 10), respectively. CONCLUSION: Hospital mortality and hospital LOS of sepsis are similar to those reported in other observational studies. Our study confirms a decline in the mortality of sepsis predicted by earlier longitudinal studies and should prompt a resurgence of epidemiological research of the sepsis syndromes in the United States. PMID- 26130581 TI - Prevention of distal extension cantilever fracture in mandibular overdentures. AB - OBJECTIVES: Fractures of distal bar extensions, supporting a mandibular overdenture, do occur with significant functional and economic consequences for the patient. This study therefore aims to evaluate the effect of different bar cross-sectional shapes and surfaces, bar extension lengths and the placement of a support rib under the distal bar extension on fracture resistance. MATERIALS AND METHODS: The 2nd moment area and static strength were calculated for 11 frequently used bar designs using finite element analysis (FEA). For two specific designs (Ackermann round O 1.8mm and Dolder-Y macro, the former with and without a support rib) additional physical static and fatigue strength tests were included. RESULTS: The FEA static strength data corresponded well to the 2nd moment area (a similar ranking when maximum allowed force was considered). The application of a rib support (Ackermann O 1.8mm) and limitations of the bar extension length (6mm for the Ackermann O 1.8mm, 8mm for the Dolder-Y macro) allowed the bars to exceed 5 * 10(6) cycles of 120 and 250N, respectively, before fracture. The region of highest stresses in FEA corresponded well with the locations of the fractures observed in static- and fatigue-testing. CONCLUSIONS: With some simple guidelines/modifications, the number of bar extension fractures can be reduced significantly. CLINICAL SIGNIFICANCE: This study focusses on distal bar extensions which improve the positioning of an implant supported overdenture. By combining laboratory testing and finite element simulations we aim to: (1) explain why fractures occur (dependent on physical characteristics of the bar), and (2) give clinical guidelines on how to prevent such fractures. PMID- 26130582 TI - Bivalent separation into univalents precedes age-related meiosis I errors in oocytes. AB - The frequency of chromosome segregation errors during meiosis I (MI) in oocytes increases with age. The two-hit model suggests that errors are caused by the combination of a first hit that creates susceptible crossover configurations and a second hit comprising an age-related reduction in chromosome cohesion. This model predicts an age-related increase in univalents, but direct evidence of this phenomenon as a major cause of segregation errors has been lacking. Here, we provide the first live analysis of single chromosomes undergoing segregation errors during MI in the oocytes of naturally aged mice. Chromosome tracking reveals that 80% of the errors are preceded by bivalent separation into univalents. The set of the univalents is biased towards balanced and unbalanced predivision of sister chromatids during MI. Moreover, we find univalents predisposed to predivision in human oocytes. This study defines premature bivalent separation into univalents as the primary defect responsible for age related aneuploidy. PMID- 26130583 TI - Comparison of outcomes after everolimus-eluting stent implantation in diabetic versus non-diabetic patients in the Tokyo-MD PCI study. AB - BACKGROUND: Diabetes mellitus (DM), especially in those requiring insulin for treatment, is known to be a risk factor for adverse events after percutaneous coronary intervention using first-generation drug-eluting stents. However, the role of DM in patients treated with everolimus-eluting stents (EES) is less known. The purpose of the present analysis was to evaluate the outcomes of treatment with EES for DM patients both requiring and not requiring insulin, and to compare them with non-DM patients. METHODS: Of patients treated with EES in the Tokyo-MD PCI study, an all-comer, multicenter, observational cohort study, we identified 199 insulin-requiring diabetics (IRDM), 575 non-insulin requiring diabetics (NIRDM), and 1092 non-diabetics (non-DM). The main outcomes were major adverse cardiovascular events (MACE) defined as a composite of all-cause death, myocardial infarction, and stroke, and target lesion revascularization (TLR). RESULTS: The cumulative incidence of MACE and TLR was significantly greater in patients with IRDM than non-DM [MACE: hazard ratio 1.97, 95% confidence interval (CI) 1.31-2.90, p<0.01; TLR: hazard ratio 3.43, 2.07-5.55, p<0.0001] according to univariate Cox proportional hazards model. After adjusting for confounders using the multivariate Cox proportional hazard model, the risk of IRDM versus non-DM for TLR remained significant (hazard ratio 1.92, 1.10-3.29, p=0.02). The incidence of TLR in NIRDM was slightly greater than that in non-DM according to univariate analysis (hazard ratio 1.65, 1.07-2.54, p=0.02). However, the risk was not statistically different in the multivariate analysis (hazard ratio 1.52, 0.97 2.35, p=0.06). CONCLUSIONS: In this all-comer, observational study, the risk of TLR was greater in IRDM compared with non-DM after EES implantation, while the increased risk for TLR from NIRDM did not reach statistical significance. PMID- 26130584 TI - Relationship between Serum Testosterone and Fracture Risk in Men: A Comparison of RIA and LC-MS/MS. AB - BACKGROUND: Serum testosterone can be measured by LC-MS/MS and RIA. We investigated whether the testosterone-fracture relationship was affected by the method of measurement. METHODS: We measured total testosterone (TT) by LC-MS/MS (TTLC-MS/MS) and RIA (TTRIA) in serum samples collected from 602 men whose incident fractures had been continuously ascertained by x-ray reports from 1989 to 2010. We measured bone mineral density (BMD) by dual-energy x-ray absorptiometry. The association between TT and fracture risk was assessed by the Cox proportional hazards model, taking into account the effect of age and BMD. RESULTS: Mean TTLC-MS/MS was higher than TTRIA by 27 ng/dL (95% CI 13-41). The concordance correlation coefficient between TTLC-MS/MS and TTRIA was 0.72 (95% CI 0.68-0.76). The Deming regression equation linking the 2 measurements was ln(TTLC MS/MS + 10) = 0.87 + 0.87 * ln(TTRIA + 10). The hazard ratio of fracture per SD decrease in TT was 1.32 (95% CI 1.12-1.54) for TTLC-MS/MS and 1.23 (1.06-1.43) for TTRIA. The correlation between predicted probabilities of fracture by TTLC MS/MS and TTRIA was r = 0.96, with the mean difference being 0.01% (95% CI -6.1% to 6.2%). Slightly more patients were classified as having hypogonadism if TTRIA was used (29% vs 26%). CONCLUSIONS: The concordance between LC-MS/MS and RIA in the measurement of serum TT was moderate. Moreover, the magnitude of association between testosterone and fracture risk in older men was largely unaffected by the method of measurement. PMID- 26130585 TI - Mass spectrometric profiling of vitamin D metabolites beyond 25-hydroxyvitamin D. AB - BACKGROUND: The frequency of measurements of vitamin D in the human population has significantly increased over the last decade because vitamin D has now been linked to many diseases, in addition to its established role in bone health. Usually, serum 25-hydroxyvitamin D concentrations are measured to assess the vitamin D status of individuals. Unfortunately, many studies investigating links between vitamin D and disease also use only this single metabolite. Intricate correlations with other vitamin D metabolites or dynamic effects of downstream metabolites may therefore be overlooked. Fortunately, powerful LC-MS/MS approaches have recently become available that can simultaneously quantify the concentrations of multiple vitamin D metabolites. These approaches are challenging, however, because of inherent instrumental problems with detection of vitamin D compounds and the low concentrations of the metabolites in biological fluids. CONTENT: This review summarizes recent mass spectrometry assays for the quantitative measurement of multiple vitamin D metabolites and their application in clinical research, with a particular focus on the low-abundance downstream metabolic species generated after the initial hydroxylation to 25-hydroxyvitamin D. SUMMARY: To study the pathobiological effects and function of vitamin D metabolites in disease, in particular in low-abundance species beyond 25 hydroxyvitamin D, we need to know their concentrations. Although detection of these vitamin D species is challenging, a number of recent mass spectrometry assays have successfully demonstrated that LC-MS/MS methods can quantify multiple vitamin D compounds over a wide dynamic range individually or as part of multimetabolite assays. PMID- 26130586 TI - An Acceptance and Commitment Therapy (ACT) group intervention for cancer survivors experiencing anxiety at re-entry. PMID- 26130587 TI - Ni-Catalyzed Regioselective Hydrocarboxylation of Alkynes with CO2 by Using Simple Alcohols as Proton Sources. AB - A mild and user-friendly Ni-catalyzed regioselective hydrocarboxylation of alkynes with CO2 (1 bar) is described. This protocol is characterized by a wide scope while obviating the need for sensitive organometallic species and by an unprecedented regioselectivity pattern using simple alcohols as proton sources. PMID- 26130588 TI - Contemporary management of cleft lip and palate in the UK. Have we reached the turning point? A commentary. PMID- 26130589 TI - Unusual cause of midfacial asymmetry: case report. PMID- 26130590 TI - Contemporary management of cleft lip and palate in the United Kingdom. Have we reached the turning point? AB - Babies born with clefts of the lip, and the alveolus or palate, or both, require multidisciplinary, highly specialised treatment from birth to early adulthood. We review the contemporary management of clefts and outline the current treatment protocol adopted by cleft networks in the United Kingdom. We also look at the level of evidence and the restructuring of services that has defined current practice. In light of the recent Cleft Care UK study, we ask whether it is now time to adopt a new philosophy towards the surgical techniques that are used. PMID- 26130591 TI - Orbital fractures in children: 10 years' experience from a tertiary centre. AB - Our aim was to examine the relations between type and site of the fracture, age of the patient, and the management and outcomes, among children diagnosed with orbital fractures at the Women's and Children's Hospital, Adelaide, during a 10 year period from 1 January 2003 to 31 December 2012. The records of 41 children whose ages ranged from 8 months to 15 years were analysed. There was a male predominance (n=33). Two most common fractures were orbital floor and multiwalled fractures, with medial wall as the second most common site. The most common cause of injury was sport, more often with increasing age. In contrast, falls were more common among young children. Fractures of the orbital roof were more common among young children, all of ours being in children 10 years old or less. Lateral wall fractures were also more common among young children and declined in frequency with increasing age. In contrast, fractures of the orbital floor and medial wall can occur at any age, though those of the medial wall were more common among older children. As children grow their behaviour and activities change, and the mechanism by which they become injured also changes. Growth and development of the craniofacial skeleton lead to differences in the patterns of fractures with age. Fractures of the orbital roof and lateral wall are more common among young children, while those of the orbital floor and medial wall can occur at any age. PMID- 26130592 TI - Regarding: "The discordance between HbA1c and glucose tolerance testing for the postpartum exclusion of diabetes following gestational diabetes". PMID- 26130593 TI - Hearing in Noise Test Brazil: standardization for young adults with normal hearing. AB - INTRODUCTION: Individuals with the same ability of speech recognition in quiet can have extremely different results in noisy environments. OBJECTIVE: To standardize speech perception in adults with normal hearing in the free field using the Brazilian Hearing in Noise Test. METHODS: Contemporary, cross-sectional cohort study. 79 adults with normal hearing and without cognitive impairment participated in the study. Lists of Hearing in Noise Test sentences were randomly in quiet, noise front, noise right, and noise left. RESULTS: There were no significant differences between right and left ears at all frequencies tested (paired t-1 test). Nor were significant differences observed when comparing gender and interaction between these conditions. A difference was observed among the free field positions tested, except in the situations of noise right and noise left. CONCLUSION: Results of speech perception in adults with normal hearing in the free field during different listening situations in noise indicated poorer performance during the condition with noise and speech in front, i.e., 0 degrees /0 degrees . The values found in the standardization of the Hearing in Noise Test free field can be used as a reference in the development of protocols for tests of speech perception in noise, and for monitoring individuals with hearing impairment. PMID- 26130594 TI - Influence of Fluorination on the Conformational Properties and Hydrogen-Bond Acidity of Benzyl Alcohol Derivatives. AB - The effect of fluorination on the conformational and hydrogen-bond (HB)-donating properties of a series of benzyl alcohols has been investigated experimentally by IR spectroscopy and theoretically with quantum chemical methods (ab initio (MP2) and DFT (MPWB1K)). It was found that o-fluorination generally resulted in an increase in the HB acidity of the hydroxyl group, whereas a decrease was observed upon o,o'-difluorination. Computational analysis showed that the conformational landscapes of the title compounds are strongly influenced by the presence of o fluorine atoms. Intramolecular interaction descriptors based on AIM, NCI and NBO analyses reveal that, in addition to an intramolecular OH???F interaction, secondary CH???F and/or CH???O interactions also occur, contributing to the stabilisation of the various conformations, and influencing the overall HB properties of the alcohol group. The benzyl alcohol HB-donating capacity trends are properly described by an electrostatic potential based descriptor calculated at the MPWB1K/6-31+G(d,p) level of theory, provided solvation effects are taken into account for these flexible HB donors. PMID- 26130595 TI - Test-treatment RCTs are sheep in wolves' clothing (Letter commenting on: J Clin Epidemiol. 2014;67:612-21). PMID- 26130596 TI - Reply to letter by Ferrante di Ruffano et al.: Patient outcomes in randomized comparisons of diagnostic tests are still the ultimate judge. PMID- 26130597 TI - To Feel or Not to Feel When My Group Harms Others? The Regulation of Collective Guilt as Motivated Reasoning. AB - Four studies tested the proposition that regulation of collective guilt in the face of harmful ingroup behavior involves motivated reasoning. Cognitive energetics theory suggests that motivated reasoning is a function of goal importance, mental resource availability, and task demands. Accordingly, three studies conducted in the United States and Israel demonstrated that high importance of avoiding collective guilt, represented by group identification (Studies 1 and 3) and conservative ideological orientation (Study 2), is negatively related to collective guilt, but only when mental resources are not depleted by cognitive load. The fourth study, conducted in Italy, demonstrated that when justifications for the ingroup's harmful behavior are immediately available, the task of regulating collective guilt and shame becomes less demanding and less susceptible to resource depletion. By combining knowledge from the domains of motivated cognition, emotion regulation, and intergroup relations, these cross-cultural studies offer novel insights regarding factors underlying the regulation of collective guilt. PMID- 26130598 TI - Perspective on unraveling the versatility of 'co-repressor' complexes. AB - A multitude of post-translational modifications take place on histones, one of the best studied being acetylation on lysine residues, which is generally associated with gene activation. During the last decades, several so-called co repressor protein complexes that carry out the reverse process, histone deacetylation, have been identified and characterized, such as the Sin3, N CoR/SMRT and NuRD complexes. Although a repressive role for these complexes in regulating gene expression is well established, accumulating evidence also points to a role in gene activation. Here, we argue that integration of various state-of the-art technologies, addressing different aspects of transcriptional regulation, is essential to unravel this apparent biological versatility of 'co-repressor' complexes. PMID- 26130599 TI - Comparative Effects of Mercury(II) and Cadmium on MutS Homolog 6(MSH6)-Mediated DNA Mismatch Binding Activities in Zebrafish (Danio rerio) Embryos. AB - MutS homolog 6 (MSH6) of the MSH2-MSH6 complex binds simple mispairs and small insertion-deletion loops (IDL) then initiates DNA mismatch repair in eukaryotes. We have shown the ability of Cd(2+) to downregulate msh2/msh6 expression in zebrafish embryos via oxidative stress. This study explored the effects of Cd(2+) and Hg(2+) on MSH6-mediated mismatch binding activities. MSH6-mediated G-T and IDL-specific binding activities were significantly inhibited at similar levels after exposing zebrafish embryos at 1 h postfertilization) to HgCl2 or CdCl2 at 1.0 to 2.5 MUM for 9 h, but MSH6 synthesis was found to be less sensitive to Hg(2+) than to Cd(2+) . Real-time RT-PCR and in situ hybridization also detected a weaker susceptibility of MSH gene transcription to Hg(2+) . The weaker response of MSH gene activities to Hg(2+) correlated with the lower oxidative stress inducing potential of Hg(2+) . Hence, Hg(2+) targets mismatch sensing capacity at protein function rather than at transcription level. PMID- 26130600 TI - Effect of peroxiredoxin II on the quality and mitochondrial activity of pre implantation bovine embryos. AB - Endogenous peroxiredoxin II (PRDX II) protein plays a vital role in early embryonic development. This study assessed the beneficial effects of exogenous PRDX II on bovine embryo development at the cellular and molecular levels. To this end, in vitro maturation (IVM) medium was supplemented with various concentrations of PRDX II (0, 6.25, 12.5, 25, 50, and 100MUg/mL). Of these, 12.5MUg/mL PRDX II was the most effective and significantly promoted embryonic development. Therefore, this concentration of PRDX II was used in subsequent experiments. The percentage of embryos that developed into Day 8 blastocysts and the total number of cells per blastocyst (38.2% and 150.6+/-5.1) was higher in the PRDX II-treated group than in the control (26.4% and 128.9+/-3.9, respectively). Moreover, the percent of TUNEL positive cells was higher (P<0.05) in the control than in the PRDX II-treated. Furthermore, PRDX II added to the IVM media increased mitochondria content in blastocysts and decreased the intracellular ROS levels in oocytes and blastocysts compared with the control (P<0.05). The expression of genes associated with blastocyst quality (CDX2 and IFNtau), antioxidant activity (SOD2), and mitochondrial activity (TFAM) was higher, whereas the expression of a gene involved in the apoptotic pathway (c FOS) was lower, in the PRDX II-treated than in the control group. In conclusion, supplementation of IVM medium with PRDX II promotes development to the blastocyst stage and improves blastocyst quality through reducing ROS, enhancing embryonic mitochondrial activity, and modulating development- related target genes expression. PMID- 26130601 TI - Liquid storage of equine semen: Assessing the effect of d-penicillamine on longevity of ejaculated and epididymal stallion sperm. AB - Short-term storage of equine sperm at 5 degrees C in an extender containing milk and/or egg yolk components is common practice in the equine breeding industry. Sperm motility, viability, DNA integrity and, consequently, fertilizing ability decline over time, partly due to reactive oxygen species (ROS) generation. We investigated whether adding the anti-oxidant d-penicillamine to a commercial milk/egg yolk extender delayed the decrease in semen quality. Semen was recovered on four consecutive days from eight 3-year old Warmblood stallions. On day 5, seven of the stallions were castrated and sperm recovered from the caudae epididymides. Ejaculated samples were split, and one portion was centrifuged and re-suspended to reduce seminal plasma content. All samples were diluted to 50millionsperm/ml and divided into two portions, one of which was supplemented with 0.5mM d-penicillamine. After 48h, 96h, 144h and 192h storage, sperm motility was assessed by computer-assisted semen analysis (CASA), viability by SYBR14/PI staining, and DNA integrity using the sperm chromatin structure assay (SCSA). d Penicillamine had no effect on motility of ejaculated sperm (P>0.05) but reduced total and progressive motility of epididymal sperm. Sperm chromatin integrity was not influenced by storage time, seminal plasma or d-penicillamine. In short, adding d-penicillamine to a commercial semen extender was neither beneficial nor detrimental to the maintenance of quality in ejaculated semen stored at 5 degrees C. The negative effect on motility of epididymal sperm may reflect differences in (membrane) physiology of spermatozoa that have not been exposed to seminal plasma. PMID- 26130602 TI - Chemical sterilisation of Bos indicus bull calves following intratesticular injection of zinc acetate: Effects on growth and concentrations of testosterone. AB - The aim of this study was to determine the effects in Bos indicus calves of intra testicular injection of either saline (n=9) or one of two doses of zinc acetate ((ZA1, 57.75mg, n=10, or ZA2, 71.75mg, n=10) or surgical castration (n=9) on circulating concentrations of testostosterone and liveweight. Human chorionic gonadotrophin (hCG, 1500IU) was administered 202 and 525 days after treatment on Day 0 and animals were slaughtered on Day 860. In animals left intact treatment with ZA reduced mean serum concentrations of testosterone (Saline: 5.58+/ 0.79ng/mL, ZA1: 1.28+/-0.27ng/mL, ZA2: 1.01+/-0.17ng/mL; P<0.001) and concentrations 48h following administration of hCG. The maximum concentration of testosterone recorded throughout the study in six out of 19 animals treated with ZA was <=0.21ng/mL. Treatment with ZA did not significantly affect live weights or carcass weights or result in any detectable scrotal lesions. Animals with concentrations of testosterone >=1.0ng/mL exhibited greater liveweights throughout most of the study and yielded heavier carcass weights (340.9+/-7.02 versus 309.3+/-6.17kg, P=0.002). It is concluded that a single, intra-testicular administration of either 57.75mg or 71.75mg of ZA was able to similarly reduce circulating concentrations of testosterone without significantly affecting liveweights or carcass weights. Treatment with ZA can result in variation in circulating concentrations of testosterone which could lead to differences in behaviour, liveweights and carcass characteristics. PMID- 26130603 TI - Carotid plaque elasticity estimation using ultrasound elastography, MRI, and inverse FEA - A numerical feasibility study. AB - The material properties of atherosclerotic plaques govern the biomechanical environment, which is associated with rupture-risk. We investigated the feasibility of noninvasively estimating carotid plaque component material properties through simulating ultrasound (US) elastography and in vivo magnetic resonance imaging (MRI), and solving the inverse problem with finite element analysis. 2D plaque models were derived from endarterectomy specimens of nine patients. Nonlinear neo-Hookean models (tissue elasticity C1) were assigned to fibrous intima, wall (i.e., media/adventitia), and lipid-rich necrotic core. Finite element analysis was used to simulate clinical cross-sectional US strain imaging. Computer-simulated, single-slice in vivo MR images were segmented by two MR readers. We investigated multiple scenarios for plaque model elasticity, and consistently found clear separations between estimated tissue elasticity values. The intima C1 (160 kPa scenario) was estimated as 125.8 +/- 19.4 kPa (reader 1) and 128.9 +/- 24.8 kPa (reader 2). The lipid-rich necrotic core C1 (5 kPa) was estimated as 5.6 +/- 2.0 kPa (reader 1) and 8.5 +/- 4.5 kPa (reader 2). A scenario with a stiffer wall yielded similar results, while realistic US strain noise and rotating the models had little influence, thus demonstrating robustness of the procedure. The promising findings of this computer-simulation study stimulate applying the proposed methodology in a clinical setting. PMID- 26130604 TI - Outcome of monochorionic diamniotic twin pregnancies followed at a single center. AB - OBJECTIVE: We aim to evaluate the outcome of a cohort of monochorionic diamniotic twin pregnancies followed from the first trimester onwards at a single center. METHOD: This was a retrospective analysis of prospectively collected data from a series of 300 monochorionic diamniotic twin pregnancies referred to our twin clinic between 2001 and 2012. Pregnancies were followed from the first trimester and fortnightly after 16 weeks of gestation. Data on pregnancy and neonatal outcome were analyzed. RESULTS: There were two surviving infants in 259/300 (86.4%) pregnancies, one survivor in 22/300 (7.3%) and no survivors in 19/300 (6.3%) with an overall mortality of 60/600 (10%). Twin-twin transfusion syndrome was diagnosed in 33 cases (11%), isolated intertwin weight discordance >= 25% in 35 (11.6%) and major congenital structural anomalies in ten (3.3%). After 32 weeks, the prospective risk of spontaneous fetal intrauterine death was one in 248 (0.4%) per pregnancy. CONCLUSIONS: Despite specific prenatal fetal monitoring and management, monochorionic diamniotic twin pregnancies have still to be considered at high risk of mortality, although the prospective risk of intrauterine death after 32 weeks is low. Twin-twin transfusion syndrome and congenital anomalies were the main risk factors for mortality. PMID- 26130605 TI - Quantifying density cues in grouping displays. AB - Perceptual grouping processes are typically studied using sparse displays of spatially separated elements. Unless the grouping cue of interest is a proximity cue, researchers will want to ascertain that such a cue is absent from the display. Various solutions to this problem have been employed in the literature; however, no validation of these methods exists. Here, we test a number of local density metrics both through their performance as constrained ideal observer models, and through a comparison with a large dataset of human detection trials. We conclude that for the selection of stimuli without a density cue, the Voronoi density metric is preferable, especially if combined with a measurement of the distance to each element's nearest neighbor. We offer the entirety of the dataset as a benchmark for the evaluation of future, possibly improved, metrics. With regard to human processes of grouping by proximity, we found observers to be insensitive to target groupings that are more sparse than the surrounding distractor elements, and less sensitive to regularity cues in element positioning than to local clusterings of target elements. PMID- 26130607 TI - An update on the validity of irisin assays and the link between irisin and hepatic metabolism. PMID- 26130606 TI - A perceptual space of local image statistics. AB - Local image statistics are important for visual analysis of textures, surfaces, and form. There are many kinds of local statistics, including those that capture luminance distributions, spatial contrast, oriented segments, and corners. While sensitivity to each of these kinds of statistics have been well-studied, much less is known about visual processing when multiple kinds of statistics are relevant, in large part because the dimensionality of the problem is high and different kinds of statistics interact. To approach this problem, we focused on binary images on a square lattice - a reduced set of stimuli which nevertheless taps many kinds of local statistics. In this 10-parameter space, we determined psychophysical thresholds to each kind of statistic (16 observers) and all of their pairwise combinations (4 observers). Sensitivities and isodiscrimination contours were consistent across observers. Isodiscrimination contours were elliptical, implying a quadratic interaction rule, which in turn determined ellipsoidal isodiscrimination surfaces in the full 10-dimensional space, and made predictions for sensitivities to complex combinations of statistics. These predictions, including the prediction of a combination of statistics that was metameric to random, were verified experimentally. Finally, check size had only a mild effect on sensitivities over the range from 2.8 to 14min, but sensitivities to second- and higher-order statistics was substantially lower at 1.4min. In sum, local image statistics form a perceptual space that is highly stereotyped across observers, in which different kinds of statistics interact according to simple rules. PMID- 26130609 TI - A novel alphaproteobacterial ectosymbiont promotes the growth of the hydrocarbon rich green alga Botryococcus braunii. AB - Botryococcus braunii is a colony-forming green alga that accumulates large amounts of liquid hydrocarbons within the colony. The utilization of B. braunii for biofuel production is however hindered by its low biomass productivity. Here we describe a novel bacterial ectosymbiont (BOTRYCO-2) that confers higher biomass productivity to B. braunii. 16S rDNA analysis indicated that the sequence of BOTRYCO-2 shows low similarity (<90%) to cultured bacterial species and located BOTRYCO-2 within a phylogenetic lineage consisting of uncultured alphaproteobacterial clones. Fluorescence in situ hybridization (FISH) studies and transmission electric microscopy indicated that BOTRYCO-2 is closely associated with B. braunii colonies. Interestingly, FISH analysis of a water bloom sample also found BOTRYCO-2 bacteria in close association with cyanobacterium Microcystis aeruginosa colonies, suggesting that BOTRYCO-2 relatives have high affinity to phytoplankton colonies. A PCR survey of algal bloom samples revealed that the BOTRYCO-2 lineage is commonly found in Microcystis associated blooms. Growth experiments indicated that B. braunii Ba10 can grow faster and has a higher biomass (1.8-fold) and hydrocarbon (1.5-fold) yield in the presence of BOTRYCO-2. Additionally, BOTRYCO-2 conferred a higher biomass yield to BOT-22, one of the fastest growing strains of B. braunii. We propose the species name 'Candidatus Phycosocius bacilliformis' for BOTRYCO-2. PMID- 26130608 TI - Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice. AB - AIMS: CD36 is an important transporter of long-chain fatty acids (LCFAs) in the myocardium. As we have reported previously, CD36-deficient patients demonstrate a marked reduction in myocardial uptake of (123)I-15-(p-iodophenyl)-(R, S)-methyl pentadecanoic acid (BMIPP), which is an analog of LCFAs, while myocardial (18)F fluorodeoxy-glucose (FDG) uptake is increased. However, it has not been clarified whether energy provision is preserved in patients with CD36 deficiency. The aims of the current study were to investigate the myocardial uptake of glucose and alterations in myocardial metabolites in wild-type (WT) and CD36 knockout (KO) mice. METHODS AND RESULTS: High-resolution positron emission tomography (PET) demonstrated markedly enhanced glucose uptake in KO mouse hearts compared with those of WT mice in real-time. The myocardial protein expression of glucose transporter protein 1 (GLUT1) was significantly enhanced in KO mice compared to WT mice, whereas that of GLUT4 was not altered. While the myocardial expression of genes involved in fatty acid metabolism did not increase in KO mice, that of genes related to glucose utilization compensatorily increased in KO mice. The metabolomic analysis of cardiac tissues revealed that the myocardial concentrations of ATP and phosphocreatine were maintained, even in KO mice. The concentration of 3-hydroxybutyric acid and mRNA expression of hydroxybutyrate dehydrogenase in the heart were significantly higher in KO than in WT mice. CONCLUSION: These data suggest that high-energy phosphate might be preserved by the increased utilization of glucose and ketone bodies in CD36KO mouse hearts under conditions of deficient LCFA uptake. PMID- 26130610 TI - Traditional medicine for the rich and knowledgeable: challenging assumptions about treatment-seeking behaviour in rural and peri-urban Nepal. AB - Traditional medicine is commonly assumed to be a crucial health care option for poor households in developing countries. However, little research has been done in Asia to quantify the reliance on traditional medicine and its determinants. This research contributes to filling in this knowledge gap using household survey data collected from 571 households in three rural and peri-urban sites in Nepal in 2012. Questions encompassed household socioeconomic characteristics, illness characteristics, and treatment-seeking behaviour. Treatment choice was investigated through bivariate analyses. Results show that traditional medicine, and especially self-treatment with medicinal plants, prevail as treatment options in both rural and peri-urban populations. Contrarily to what is commonly assumed, high income is an important determinant of use of traditional medicine. Likewise, knowledge of medicinal plants, age, education, gender and illness chronicity were also significant determinants. The importance of self-treatment with medicinal plants should inform the development of health policy tailored to people's treatment-seeking behaviour. PMID- 26130611 TI - Changes in computed tomography values of mandibular condyle and temporomandibular joint disc position after sagittal split ramus osteotomy. AB - PURPOSE: The purpose of this study was to evaluate change in computed tomography (CT) value of condyle and temporomandibular joint (TMJ) disc position after sagittal split ramus osteotomy (SSRO) setback surgery, retrospectively. SUBJECTS AND METHODS: The subjects were 76 patients (152 condyles) who underwent bilateral SSRO setback surgery. They were divided into 2 groups (43 symmetric patients and 33 asymmetric patients). CT values (pixel values) of 5 sites of the condyle and condylar width, length, horizontal angle were measured pre-operatively and 1 year post-operatively. Disc position was classified as anterior disc displacement, anterior type, fully covered type and posterior type, preoperatively and postoperatively using magnetic resonance imaging (MRI). RESULTS: In maximum CT value at the center of the condyle, post-operative value was significantly lower than pre-operative value bilaterally (Deviation side: P = 0.0003, Non-deviation side: P = 0.0003) in asymmetry group. In minimum CT value at the center of the condyle, the post-operative value was significantly lower than the pre-operative value bilaterally (Deviation side: P = 0.0309, Non-deviation side: P = 0.0004) in the symmetry group. With regard to maximum CT value at the lateral site of the condyle in the deviation side, the value for the anterior disc displacement group was significantly larger than that of the posterior type pre-operatively (P = 0.0123). CT value of the anterior disc displacement group was significantly larger than those of some other areas pre- and post-operatively (P < 0.05). CONCLUSION: This study suggested that CT value of condylar bone changes after 1 year in SSRO and anterior disc displacement may partially affect the CT value of the condyle in the TMJ in mandibular prognathism patients. PMID- 26130612 TI - Thromboelastometry: A contribution to perioperative free-flap management. AB - BACKGROUND: Microvascular tissue transfer is a fundamental part of reconstructive surgery. Different perioperative anticoagulation regimens exist, influencing hemostatic parameters. Since bleeding and thrombosis are major reasons for revision procedures and flap loss, current practice regarding anticoagulative treatment needs further refinement. Thromboelastometry has been demonstrated as worthwhile in the determination of alterations of the anticoagulation cascade. We evaluated this aspect of thromboelastometry for free flap surgery. METHODS: Thirty-five patients undergoing free-flap surgery were enrolled in this study. Blood samples were obtained at three time points: at the beginning of surgery, at time of anastomosis and after 24 h. At each time point, thromboelastometry with special regard to clotting times for the intrinsic and extrinsic paths of coagulation was immediately performed. Global coagulation markers and clinical parameters were collected simultaneously. RESULTS: Hemostatic changes were deducible using thromboelastometry perioperatively. Measured parameters differed significantly over time (p < 0.05). Heparin therapy showed a significant effect on the measured slope of INTEM-clotting times (p < 0.001). Altered values of thromboelastometry suggested non-inferiority to standard testing. Neither standard testing nor thromboelastometry were capable of predicting adverse events such as thrombosis, bleeding or flap loss (p > 0.05). CONCLUSIONS: Thromboelastometry monitors hemostatic effects almost in real-time and could serve as a supplementary tool in microvascular tissue transfer once its use has been standardized. The utilization of thromboelastometry allows for assessment of the anticoagulation needs of individual patients undergoing free flap surgery, which is frequently accompanied by hemostatic changes in the perioperative setting. Our findings implicate further validation of thromboelastometry in free flap surgery. PMID- 26130613 TI - The free energy of mechanically unstable phases. AB - Phase diagrams provide 'roadmaps' to the possible states of matter. Their determination traditionally rests on the assumption that all phases, even unstable ones, have well-defined free energies under all conditions. However, this assumption is commonly violated in condensed phases due to mechanical instabilities. This long-standing problem impedes thermodynamic database development, as pragmatic attempts at solving this problem involve delicate extrapolations that are highly nonunique and that lack an underlying theoretical justification. Here we propose an efficient computational solution to this problem that has a simple interpretation, both as a topological partitioning of atomic configuration space and as a minimally constrained physical system. Our natural scheme smoothly extends the free energy of stable phases, without relying on extrapolation, thus enabling a formal assessment of widely used extrapolation schemes. PMID- 26130614 TI - beta3-Adrenoceptor Impairs Mitochondrial Biogenesis and Energy Metabolism During Rapid Atrial Pacing-Induced Atrial Fibrillation. AB - BACKGROUND: The beta3-adrenoceptor (beta3-AR) is implicated in cardiac remodeling. Since metabolic dysfunction due to loss of mitochondria plays an important role in heart diseases, we examined the effects of beta3-AR on mitochondrial biogenesis and energy metabolism in atrial fibrillation (AF). METHODS: Atrial fibrillation was created by rapid atrial pacing in adult rabbits. Rabbits were randomly divided into 4 groups: control, pacing (P7), beta3-AR antagonist (L748337), and beta3-AR agonist (BRL37344) groups. Atrial effective refractory period (AERP) and AF induction rate were measured. Atrial concentrations of adenine nucleotides and phosphocreatine were quantified through high-performance liquid chromatography. Mitochondrial DNA content was determined. Real-time polymerase chain reaction and Western blot were used to examine the expression levels of signaling intermediates related to mitochondrial biogenesis. RESULTS: After pacing for 7 days, beta3-AR was significantly upregulated, AERP was reduced, and the AF induction rate was increased. The total adenine nucleotides pool was significantly reduced due to the decrease in adenosine triphosphate (ATP). The P7 group showed decreased activity of F0F1-ATPase. Mitochondrial DNA content was decreased and mitochondrial respiratory chain subunits were downregulated after pacing. Furthermore, expression of transcription factors involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (Tfam), was lower in the P7 group in response to beta3-AR activation. Further stimulation of beta3-AR with BRL37344 exacerbated these effects, together with a significant decrease in the levels of phosphocreatine. In contrast, inhibition of beta3-AR with L748337 partially restored mitochondrial biogenesis and energy metabolism of atria in the paced rabbits. CONCLUSION: The activation of beta3-AR contributes to atrial metabolic remodeling via transcriptional downregulation of PGC-1alpha/NRF 1/Tfam pathway that are involved in mitochondrial biogenesis, which ultimately perturbs mitochondrial function in rapid pacing-induced AF. The beta3-AR is therefore a potential novel therapeutic target for the treatment or prevention of AF. PMID- 26130615 TI - The RSK Inhibitor BIX02565 Limits Cardiac Ischemia/Reperfusion Injury. AB - AIMS: During ischemia/reperfusion (I/R), ribosomal S6 kinase (RSK) activates Na(+)/H(+) exchanger 1 (NHE1) by phosphorylating NHE1 at serine 703 (pS703-NHE1), which promotes cardiomyocyte death and injury. Pharmacologic inhibition of NHE1 effectively protects animal hearts from I/R. However, clinical trials using NHE1 inhibitors failed to show benefit in patients with acute myocardial infarction (MI). One possible explanation is those inhibitors block both agonist-stimulated activity (increasing I/R injury) and basal NHE1 activity (necessary for cell survival). We previously showed that dominant-negative RSK (DN-RSK) selectively blocked agonist-stimulated NHE1 activity. Therefore, we hypothesized that a novel RSK inhibitor (BIX02565) would blunt agonist-stimulated NHE1 and protect hearts from I/R. METHODS AND RESULTS: Serum/angiotensin II-stimulated pS703-NHE1 was significantly decreased by BIX02565 in cultured cells. Intracellular pH recovery assay showed that BIX02565 selectively inhibited serum-stimulated NHE1 activity. Ischemia/reperfusion decreased left ventricular-developed pressure (LVDP; inhibited) to 8.7% of the basal level in non-transgenic littermate control (NLC) mouse hearts, which was significantly improved (44.6%) by BIX02565. Similar protection was observed in vehicle-treated, cardiac-specific DN-RSK-Tg mice (43%). No additional protective effect was seen in BIX02565-treated DN-RSK-Tg hearts. BIX02565 also improved LVDP in cardiac-specific wild-type (WT)-RSK-Tg mouse hearts (7.4%-40.9%, P < .01). Finally, Western Blotting results confirmed DN-RSK and BIX02565 significantly decreased I/R-induced pS703-NHE1. CONCLUSION: The RSK plays a crucial role in I/R-induced activation of NHE1 and cardiac injury. The RSK inhibition may provide an alternative target for patients with MI. PMID- 26130616 TI - Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis. AB - BACKGROUND: The development of heart failure is associated with changes in the size, shape, and structure of the heart that has a negative impact on cardiac function. These pathological changes involve excessive extracellular matrix deposition within the myocardial interstitium and myocyte hypertrophy. Alterations in fibroblast phenotype and myocyte activity are associated with reprogramming of gene transcriptional profiles that likely requires epigenetic alterations in chromatin structure. The aim of our work was to investigate the potential of a currently licensed anticancer epigenetic modifier as a treatment option for cardiac diseases associated with hypertension-induced cardiac hypertrophy and fibrosis. METHODS AND RESULTS: The effects of DNA methylation inhibition with 5-azacytidine (5-aza) were examined in a human primary fibroblast cell line and in a spontaneously hypertensive rat (SHR) model. The results from this work allude to novel in vivo antifibrotic and antihypertrophic actions of 5 aza. Administration of the DNA methylation inhibitor significantly improved several echocardiographic parameters associated with hypertrophy and diastolic dysfunction. Myocardial collagen levels and myocyte size were reduced in 5-aza treated SHRs. These findings are supported by beneficial in vitro effects in cardiac fibroblasts. Collagen I, collagen III, and alpha-smooth muscle actin were reduced in a human ventricular cardiac fibroblast cell line treated with 5-aza. CONCLUSION: These findings suggest a role for epigenetic modifications in contributing to the profibrotic and hypertrophic changes evident during disease progression. Therapeutic intervention with 5-aza demonstrated favorable effects highlighting the potential use of this epigenetic modifier as a treatment option for cardiac pathologies associated with hypertrophy and fibrosis. PMID- 26130617 TI - Satisfaction with Care of Patients on Hemodialysis. AB - BACKGROUND AND OBJECTIVES: Little is known about patients receiving dialysis who respond to satisfaction and experience of care surveys and those who do not respond, nor is much known about the corollaries of satisfaction. This study examined factors predicting response to Dialysis Clinic, Inc. (DCI)'s patient satisfaction survey and factors associated with higher satisfaction among responders. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENT: A total of 10,628 patients receiving in-center hemodialysis care at 201 DCI facilities between January 1, 2011, and December 31, 2011, aged >=18 years, treated during the survey administration window, and at the facility for >=3 months before survey administration. Primary outcome was response to at least one of the nine survey questions; secondary outcome was overall satisfaction with care. RESULTS: Response rate was 77.3%. In adjusted logistic regression (odds ratios with 95% confidence intervals), race other than black (white race, 1.23 [1.10 to 1.37]), missed treatments (1.16 [1.02 to 1.32]) or shortened treatments (>=5 treatments, 1.40 [1.22 to 1.60]), more hospital days (>3 days in the last 3 months, 1.89 [1.66 to 2.15]), and lower serum albumin (albumin level <3.5 g/dl, 1.4 [1.28 to 1.73]) all independently predicted nonresponse. In adjusted linear regression, the following were more satisfied with care: older patients (age >=63 years, 1.84 [1.78 to 1.90]; age <63 years, 1.91 [1.86 to 1.97]; P<0.001), white patients (1.76 [1.71 to 1.81]) versus black patients (1.93 [1.88 to 1.99]) or those of other race (1.93 [1.83 to 2.03]) (P<0.001), patients with shorter duration of dialysis (<=2.5 years, 1.79 [1.73 to 1.84]; >2.5 years, 1.96 [1.91 to 2.02]; P<0.001), patients who had missed one or fewer treatments (1.83 [1.78 to 1.88]) versus those who had missed more than one treatment (1.92 [1.85 to 1.98]; P=0.002) and those who had shortened treatment (for one treatment or less, 1.84 [1.77 to 1.90]; for two to four treatments, 1.87 [1.81 to 1.93]; for five or more treatments, 1.92 [1.87 to 1.98]; P=0.004). CONCLUSIONS: Survey results represent healthier and more adherent patients on hemodialysis. Shorter survey administration windows were associated with higher response rates. Older, white patients with shorter dialysis vintage were more satisfied. PMID- 26130618 TI - Childhood Experiences of Physical, Emotional and Sexual Abuse among College Students in South India. AB - OBJECTIVES: To document the prevalence of physical, emotional and sexual abuse during childhood among college students. METHODS: The study was conducted among college students of Puducherry, South India. Stratified random sampling was done to select colleges. Data were gathered using the adapted 'Ministry of Women and Child Development Questionnaire on Child Abuse for Young adults'. RESULTS: A total of 936 college students completed the questionnaire. Mean +/- SD age of the participants was 19.2 +/- 1.1 years. Half (48%) of the participants reported being mocked because of their physical appearance. In all, 56% (524/936) of the participants reported that they were beaten during their childhood, of which 13.4% (70/524) required medical treatment. Around 10% reported someone exposing his/her private parts to them, while in 6.4% of the cases, the perpetrator forced the study participants to expose their private parts. CONCLUSIONS: Emotional, physical and sexual abuse is common in childhood and demands prompt interventions at the familial, community and political levels. PMID- 26130619 TI - A decline of Haemophilus influenzae type b meningitis in Papua New Guinean children despite low vaccination coverage. PMID- 26130620 TI - Testicular Schistosomiasis Mimicking Malignancy in a Child: A Case Report. AB - Schistosomiasis is an important communicable disease in the developing world. However, testicular schistosomiasis is an extremely rare condition. We report a case of testicular schistosomiasis mimicking testicular tumour in a 13 year old who presented with huge unilateral testicular mass. The dilemma encountered in the diagnosis and treatment of this child is presented to highlight the need for high index of suspicion of this pathology in children with testicular mass presenting from schistosomiasis-endemic areas. PMID- 26130621 TI - Clinical, nutritional and immunological characteristics of HIV-infected children in an area of high HIV prevalence. AB - OBJECTIVES: To evaluate the clinical, nutritional and neurodevelopment status of HIV-infected children in a high HIV prevalence area. METHODS: All HIV-infected children under 15 years of age attending an outpatient clinic of Mozambique between April and May 2010 were recruited. Clinical data were collected and physical examination was performed. RESULTS: In all, 140 children were recruited. The median age at HIV diagnosis was 2.1 years. Fifty-one percent of the children were classified in WHO clinical Stages 3 or 4. Median age of antiretroviral treatment commencement was 3.9 years. Overall, 68% were undernourished, mainly stunted. Forty-four percent failed to pass the national psychomotor developmental test. CONCLUSIONS: The pathways for early HIV diagnosis and start of antiretrovirals in children should be improved in Mozambique. Malnutrition, especially stunting, and developmental delay were highly prevalent. Further research focused on early diagnosis of neurocognitive disorders and on the indications of antiretroviral treatment commencement based on chronic malnutrition is required. PMID- 26130622 TI - Urine Nested Polymerase Chain Reaction in Neonatal Septicemia. AB - This cross-sectional study was done to evaluate diagnostic efficacy of urine nested polymerase chain reaction (PCR) using broad-range 16SrDNA PCR-based amplification, followed by restriction analysis and sequencing in neonatal septicemia. The study included 50 babies; 48% had vaginal delivery, 46% were preterm, 20% had a history of prolonged rupture of membranes and 56% were low birth weight (<=2500 g). Clinical presentations were lethargy (96%), respiratory distress (80%) and bleeding diathesis (16%). Absolute neutrophil count <1800/mm(3) was observed in 60%, and positive C-reactive protein in 46%. Thirty neonates had positive blood culture, and Klebsiella pneumoniae (22%) was the predominant organism. Nested urine PCR was positive in 38 (76%) and detected bacterial DNA in 8 neonates with negative blood cultures. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of nested PCR were 100, 60, 78.9, 100 and 84%, respectively, compared with blood culture. Nested PCR can detect most bacteria in single assay and identify unusual and unexpected causal agents. PMID- 26130623 TI - High-dose Oral Ambroxol for Early Treatment of Pulmonary Acute Respiratory Distress Syndrome: an Exploratory, Randomized, Controlled Pilot Trial. AB - OBJECTIVE: To evaluate efficacy of high-dose oral ambroxol in acute respiratory distress syndrome (ARDS) with respect to ventilator-free days (VFD). DESIGN: Prospective, randomized, placebo-controlled, blinded pilot trial. PATIENTS: Sixty six mechanically ventilated patients (1 month to 12 years) with ARDS who were hand-ventilated for <24 hr before pediatric intensive care unit admission. INTERVENTIONS: Patients randomized to oral ambroxol (40 mg/kg/day, in four divided doses) (n = 32) or placebo (n = 34) until 10 days, extubation or death whichever is earlier. MEASUREMENTS AND MAIN RESULTS: Majority (91%) had pneumonia and bronchiolitis. Two study groups were similar in baseline characteristics. Mean partial pressure of arterial oxygen/fraction of inspired oxygen and oxygenation index were >175 and <10, respectively, with no difference in the two study groups. VFD were similar in the two study groups. Overall mortality was 26%. No adverse events were noted with ambroxol. CONCLUSIONS: Among ventilated pulmonary ARDS patients with oxygenation index of <10, mortality was 26%. Ambroxol did not improve VFD. Study with higher and more frequently administered doses of ambroxol in larger sample is suggested after having generated relevant pharmacokinetic data among critically ill children. PMID- 26130624 TI - Failed Surgical Management of Acute Proximal Fifth Metatarsal (Jones) Fractures: A Retrospective Case Series and Literature Review. AB - Nonunion, delayed union, and refracture after operative treatment of acute proximal fifth metatarsal fractures in athletes is uncommon. This study was a failure analysis of operatively managed acute proximal fifth metatarsal fractures in healthy athletes. We identified 149 patients who underwent operative treatment for fifth metatarsal fractures. Inclusion criteria isolated skeletally mature, athletic patients under the age of 40 with a minimum of 1-year follow-up. Patients were excluded with tuberosity fractures, fractures distal to the proximal metaphyseal-diaphyseal region of the fifth metatarsal, multiple fractures or operative procedures, fractures initially treated conservatively, and medical comorbidities/risk factors for nonunion. Fifty-five patients met the inclusion/exclusion criteria. Four (7.3%) patients required a secondary operative procedure due to refracture. The average time to refracture was 8 months. All refractures were associated with bent screws and occurred in male patients who participated in professional basketball, professional volleyball, and college football. The average time for release to progressive weight-bearing was 6 weeks. Three patients were revised to a bigger size screw and went on to union. One patient was revised to the same-sized screw and required a second revision surgery for nonunion. All failures were refractures in competitive athletes who were initially treated with small diameter solid or cannulated stainless steel screws. The failures were not associated with early postoperative weight-bearing protocol. Maximizing initial fixation stiffness may decrease the late failure rate in competitive athletes. More clinical studies are needed to better understand risk factors for failure after screw fixation in the competitive, athletic population. LEVEL OF EVIDENCE: Prognostic, Level IV: Case series. PMID- 26130625 TI - Perioperative Glycemic Control and the Effect on Surgical Site Infections in Diabetic Patients Undergoing Foot and Ankle Surgery. AB - INTRODUCTION: Diabetes mellitus is one of the leading causes of hyperglycemia in the perioperative setting. Hyperglycemia has been shown to cause increased risk of surgical site infections (SSIs) in multiple surgical specialties, but to our knowledge it has not been investigated for orthopaedic foot and ankle surgery. The aim of this study was to determine if hyperglycemia increased the rate of SSI in elective, diabetic patients that required perioperative hospitalization. METHODS: A total of 348 consecutive inpatients after foot and ankle surgery were retrospectively evaluated. Patients who had a random serum glucose >=200 mg/dL during the admission (Group 1) were compared to patients whose serum glucose never exceeded 200 mg/dL (Group 2). RESULTS: Our 2 groups were similar with regard to age, gender, and body mass index. Twenty-one of 176 patients (11.9%) whose serum glucose was >=200 mg/dL during the admission developed an SSI as compared to 9 of 172 patients (5.2%) whose serum glucose remained <200 mg/dL (odds ratio = 2.45; 95% confidence interval = 1.09-5.52;, P = .03). DISCUSSION: Perioperative hyperglycemia >=200 mg/dL is associated with increased rates of SSI after foot and ankle surgery. Communication with medical consultants is paramount in an effort to improve perioperative glycemic management and reduce the rate of SSI. LEVELS OF EVIDENCE: Prognostic, Level III: Case Control. PMID- 26130626 TI - Clinical Relevance of Serotonin Receptor Splice Variant Distribution in Human Colon. PMID- 26130627 TI - Practical Methods to Assess Chronic Constipation. PMID- 26130628 TI - Unmet Needs in the Treatment of Gastroesophageal Reflux Disease. AB - Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder. Proton pump inhibitors have profoundly revolutionized the treatment of GERD. However, several areas of unmet need persist despite marked improvements in the ther-apeutic management of GERD. These include the advanced grades of erosive esophagitis, nonerosive reflux disease, main-tenance treatment of erosive esophagitis, refractory GERD, postprandial heartburn, atypical and extraesophageal manifestations of GERD, Barrett's esophagus, chronic protein pump inhibitor treatment, and post-bariatric surgery GERD. Consequently, any fu-ture development of novel therapeutic modalities for GERD (medical, endoscopic, or surgical), would likely focus on the afore-mentioned areas of unmet need. PMID- 26130629 TI - Prokinetics in the Management of Functional Gastrointestinal Disorders. AB - A variety of common and some not common gastrointestinal syndromes are thought to be based on impaired gut motility. For some, the role of motility is well defined, for others and the functional gastrointestinal disorders, in particular, the role of hy-po- or dysmotility remains unclear. Over the years pharmacological and physiological laboratories have developed drugs which stimulate gut motility; many have been evaluated in motility and functional disorders with what can best be described as mixed results. Lack of receptor specificity and resultant expected and unexpected adverse events have led to the demise of some of these agents. Newer, more selective agents offer promise but the heterogeneity of the clinical disorders they target continues to pose a formidable challenge to drug development in this area. PMID- 26130631 TI - The Effects of an Extract of Atractylodes Japonica Rhizome, SKI3246 on Gastrointestinal Motility in Guinea Pigs. AB - BACKGROUND/AIMS: There are limited therapeutic options available for irritable bowel syndrome with diarrhea (IBS-D). We tested the effects of Atractylodes japonica rhizome, a perennial plant native to North Asia, on both upper and lower gastrointestinal (GI) motility in guinea pigs. METHODS: The extract of A. japonica rhizome was administered orally at different doses to test its effects on upper GI motility as determined from charcoal transit in native guinea pigs and in guinea pigs pretreated with thyrotropin-releasing hormone or mustard oil. Regarding its effect on lower GI motility, the removed guinea pig colon was suspended in a chamber containing Krebs-Henseleit solution and the transit time of artificial feces was measured with various dilutions of the extract. As for in vivo assay, weight and number of fecal pellets expelled were determined under the same drug preparation used in upper GI motility experiment. RESULTS: The extract of A. japonica rhizome had no significant effect on upper GI motility in either normal or altered physiological states. However, the extract increased colonic transit time in the in vitro model. In the fecal expulsion study, the cumulative weight and number of pellets did not differ significantly between the control group and groups treated with the extracts. In the animals pretreated in vivo with thyrotropin-releasing hormone, however, the weight and number of fecal pellets were sig-nificantly decreased in animals treated with 300 mg/kg and 600 mg/kg doses of extract. CONCLUSIONS: Our findings suggest that the extract of A. japonica rhizome can be a potential agent for IBS-D. PMID- 26130630 TI - Optical Tools to Investigate Cellular Activity in the Intestinal Wall. AB - Live imaging has become an essential tool to investigate the coordinated activity and output of cellular networks. Within the last decade, 2 Nobel prizes have been awarded to recognize innovations in the field of imaging: one for the discovery, use, and optimization of the green fluorescent protein (2008) and the second for the development of super-resolved fluorescence microscopy (2014). New advances in both optogenetics and microscopy now enable researchers to record and manipulate ac-tivity from specific populations of cells with better contrast and resolution, at higher speeds, and deeper into live tissues. In this review, we will discuss some of the recent developments in microscope technology and in the synthesis of fluorescent probes, both synthetic and genetically encoded. We focus on how live imaging of cellular physiology has progressed our under-standing of the control of gastrointestinal motility, and we discuss the hurdles to overcome in order to apply the novel tools in the field of neurogastroenterology and motility. PMID- 26130632 TI - Distribution of 5-HT3, 5-HT4, and 5-HT7 Receptors Along the Human Colon. AB - BACKGROUND/AIMS: Several disorders of the gastrointestinal tract are associated with abnormal serotonin (5-HT) signaling or metabolism where the 5-HT3 and 5-HT4 receptors are clinically relevant. The aim was to examine the distribution of 5 HT3, 5-HT4, and 5-HT7 receptors in the normal human colon and how this is associated with receptor interacting chaperone 3, G protein coupled receptor kin ases, and protein LIN-7 homologs to extend previous observations limited to the sigmoid colon or the upper intestine. METHODS: Samples from ascending, transverse, descending, and sigmoid human colon were dissected into 3 separate layers (mucosa, lon-gitudinal, and circular muscles) and ileum samples were dissected into mucosa and muscle layers (n = 20). Complementary DNA was synthesized by reverse transcription from extracted RNA and expression was determined by quantitative or end point polymerase chain reaction. RESULTS: The 5 HT3 receptor subunits were found in all tissues throughout the colon and ileum. The A subunit was detected in all sam-ples and the C subunit was expressed at similar levels while the B subunit was expressed at lower levels and less frequently. The 5-HT3 receptor E subunit was mainly found in the mucosa layers. All splice variants of the 5-HT4 and 5-HT7 receptors were expressed throughout the colon although the 5-HT4 receptor d, g, and i variants were expressed less often. CONCLUSIONS: The major differences in 5-HT receptor distribution within the human colon are in relation to the mucosa and muscular tissue layers where the 5-HT3 receptor E subunit is predominantly found in the mucosal layer which may be of therapeutic relevance. PMID- 26130633 TI - How the Body Position Can Influence High-resolution Manometry Results in the Study of Esophageal Dysphagia and Gastroesophageal Reflux Disease. AB - BACKGROUND/AIMS: The body position can influence esophageal motility data obtained with high-resolution manometry (HRM). To examine whether the body position influences HRM diagnoses in patients with esophageal dysphagia and gastroesophageal reflux disease (GERD). METHODS: HRM (Manoscan) was performed in 99 patients in the sitting and supine positions; 49 had dysphagia and 50 had GERD as-sessed by 24-hour pH monitoring. HRM plots were analyzed according to the Chicago classification. RESULTS: HRM results varied in the final diagnoses of the esophageal body (EB) in patients with dysphagia (P = 0.024), the result being more distal spasm and weak peristalsis while sitting. In patients with GERD, the HRM diagnoses of the lower esophageal sphinc-ter (LES), the esophagogastric junction (EGJ) morphology, and EB varied depending on the position; (P = 0.063, P = 0.017, P = 0.041 respectively). Hypotensive LES, EGJ type III (hiatal hernia), and weak peristalsis were more frequently identified in the sitting position. The reliability (kappa) of the position influencing HRM diagnoses was similar in dysphagia and GERD ("LES diagnosis": dysphagia 0.32 [0.14-0.49] and GERD 0.31 [0.10-0.52], P = 0.960; "EB diagnosis": dysphagia 0.49 [0.30-0.69] and GERD 0.39 [0.20-0.59], P = 0.480). The reliability in "EGJ morphology" studies was higher in dysphagia 0.81 (0.68-0.94) than in GERD 0.55 (0.37-0.73), P = 0.020. CONCLUSIONS: HRM results varied according to the position in patients with dysphagia and GERD. Weak peristalsis was more frequently diagnosed while sitting in dysphagia and GERD. Hypotensive LES and EGJ type III (hiatal hernia) were also more frequently diagnosed in the sitting position in patients with GERD. PMID- 26130634 TI - Is the Impedance Baseline Helpful in the Evaluation of Globus Patients? AB - BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) has been suggested to be responsible for 23-68% of globus cases. The impedance baseline (IB) acquired by 24-hour multichannel intraluminal impedance monitoring has been proven to represent esophageal mucosal integrity. We aimed to investigate whether the IB is helpful for evaluating globus patients. METHODS: Twenty-four-hour multichannel intraluminal impedance pH tracings (MII-pH) were evaluated in globus patients. Differences in the IB between the acid reflux, non-acid reflux, and no reflux groups were analyzed. Receiver operating characteristic (ROC) curves were obtained to determine the optimal measurement point from the lower esophageal sphincter (LES). RESULTS: A total of 62 patients were analyzed. MII-pH showed that acid reflux, non-acid reflux, and no reflux were present in 13, 5, and 44 patients, respectively. The acid reflux group had a significantly lower IB than the other groups at a location 3 cm from the LES. ROC curve analysis revealed that placement at a position 3 cm from the LES resulted in moderate diagnostic accuracy (area under the curve = 0.88). When we set 2500 Omega as the cut-off value for acid reflux at a position 3 cm from the LES, the additional diagnostic yield for acid reflux was increased by 19.4% compared with that obtained by MII pH. CONCLUSIONS: IB is complementary to pH findings enabling identification of a subset of patients with co-existing acid reflux. Catheter place-ment at a location 3 cm from the LES and a cut-off value of 2500 Omega may be reasonable criteria for estimating acid reflux. PMID- 26130635 TI - Supragastric Belching: Prevalence and Association With Gastroesophageal Reflux Disease and Esophageal Hypomotility. AB - BACKGROUND/AIMS: Supragastric belching (SGB) is a phenomenon during which air is sucked into the esophagus and then rapidly expelled through the mouth. Patients often complain of severely impaired quality of life. Our objective was to establish the prevalence of ex-cessive SGB within a high-volume gastrointestinal physiology unit, and evaluate its association with symptoms, esophageal mo-tility and gastresophageal reflux disease. METHODS: We established normal values for SGB by analyzing 24-hour pH-impedance in 40 healthy asymptomatic volunteers. We searched 2950 consecutive patient reports from our upper GI Physiology Unit (from 2010-2013) for SGB. Symptoms were re-corded by a standardized questionnaire evaluating for reflux, dysphagia, and dyspepsia symptoms. We reviewed the predom inant symptoms, 24-hour pH-impedance and high-resolution esophageal manometry results. RESULTS: Excessive SGB was defined as > 13 per 24 hours. We identified 100 patients with excessive SGB. Ninety-five percent of these patients suffered from typical reflux symptoms, 86% reported excessive belching, and 65% reported dysphagia. Forty-one per-cent of patients with excessive SGB had pathological acid reflux. Compared to the patients with normal acid exposure these patients trended towards a higher number of SGB episodes. Forty-four percent of patients had esophageal hypomotility. Patients with hypomotility had a significantly higher frequency of SGB compared to those with normal motility (118.3 +/- 106.1 vs 80.6 +/- 75.7, P = 0.020). CONCLUSIONS: Increased belching is rarely a symptom in isolation. Pathological acid exposure and hypomotility are associated with more SGB frequency. Whether SGB is a disordered response to other esophageal symptoms or their cause is unclear. PMID- 26130636 TI - Effects of Intraduodenal Infusions of L-phenylalanine and L-glutamine on Antropyloroduodenal Motility and Plasma Cholecystokinin in Healthy Men. AB - BACKGROUND/AIMS: Dietary proteins have potent eating-inhibitory and glucose lowering effects, which may be mediated via effects of amino acids on gastrointestinal hormone and motor function, although little information is available. We have now evaluated the effects of L-phenylalanine (L-Phe) and L glutamine (L-Gln) on antropyloroduodenal motility and plasma cholecystokinin (CCK) concen-trations. METHODS: Two double-blind, 3-way cross-over studies were performed, each including 10 healthy, normal-weight men. We determined the antropyloroduodenal motor and plasma CCK responses to 90-minute intraduodenal infusions of L-Phe (study A) or L-Gln (study B), each at 0.15 kcal/min (total 13.5 kcal), or 0.45 kcal/min (total 40.5 kcal), or saline (control), in randomized fashion. RESULTS: Intraduodenal L-Phe at 0.45 kcal/min, but not at 0.15 kcal/min, suppressed antral (P < 0.01), and stimulated phasic (P < 0.01), but not tonic, pyloric, or duodenal pressures, while L-Phe at both 0.15 kcal/min and 0.45 kcal/min stimulated plasma CCK. In contrast, L-Gln had no effect on antral, duodenal or pyloric pressures, or plasma CCK. CONCLUSIONS: Intraduodenal infusions of L-Phe and L-Gln, in doses of 0.15 kcal/min and 0.45 kcal/min for 90 minutes, have different effects on antropyloroduodenal motility and CCK in normal weight men. The modulation of antral and pyloric pressures and CCK may contribute to the eating-inhibitory effects of oral L-Phe, possibly through the slowing of gastric emptying. PMID- 26130637 TI - Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia. AB - BACKGROUND/AIMS: Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. METHODS: Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspep-tic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. RESULTS: We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as >= 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. CONCLUSIONS: DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with com-parable safety. PMID- 26130638 TI - Regional Gastrointestinal Transit Times in Patients With Carcinoid Diarrhea: Assessment With the Novel 3D-Transit System. AB - BACKGROUND/AIMS: The paucity of knowledge regarding gastrointestinal motility in patients with neuroendocrine tumors and carcinoid diarrhea re-stricts targeted treatment. 3D-Transit is a novel, minimally invasive, ambulatory method for description of gastrointestinal motility. The system has not yet been evaluated in any group of patients. We aimed to test the performance of 3D-Transit in patients with carcinoid diarrhea and to compare the patients' regional gastrointestinal transit times (GITT) and colonic motility patterns with those of healthy subjects. METHODS: Fifteen healthy volunteers and seven patients with neuroendocrine tumor and at least 3 bowel movements per day were inves-tigated with 3D-Transit and standard radiopaque markers. RESULTS: Total GITT assessed with 3D-Transit and radiopaque markers were well correlated (Spearman's rho = 0.64, P = 0.002). Median total GITT was 12.5 (range: 8.5-47.2) hours in patients versus 25.1 (range: 13.1-142.3) hours in healthy (P = 0.007). There was no difference in gastric emptying (P = 0.778). Median small intestinal transit time was 3.8 (range: 1.4-5.5) hours in patients versus 4.4 (range: 1.8-7.2) hours in healthy subjects (P = 0.044). Median colorectal transit time was 5.2 (range: 2.9 40.1) hours in patients versus 18.1 (range: 5.0-134.0) hours in healthy subjects (P = 0.012). Median frequency of pansegmental co-lonic movements was 0.45 (range: 0.03-1.02) per hour in patients and 0.07 (range: 0-0.61) per hour in healthy subjects (P = 0.045). CONCLUSIONS: Three-dimensional Transit allows assessment of regional GITT in patients with diarrhea. Patients with carcinoid diarrhea have faster than normal gastrointestinal transit due to faster small intestinal and colorectal transit times. The latter is caused by an increased frequency of pansegmental colonic movements. PMID- 26130639 TI - Intestinal Pseudoobstruction Caused by Chronic Lyme Neuroborreliosis. A Case Report. AB - Chronic intestinal pseudoobstruction is often classified as idiopathic. The condition is associated with poor quality of life and high morbidity, and treatment options are often unsatisfactory. A case of chronic intestinal pseudoobstruction in a 66-year-old woman, presenting with back and abdominal pain, urinary retention and severe constipation is described. The patient lived in an area in which Lyme disease is endemic and had been bitten by ixodes ticks. Intrathecal synthesis of anti-borrelia IgM and IgG and lymphocytosis in the cerebrospinal fluid was found, consistent with chronic Lyme neuroborreliosis since symptoms had lasted for more than six months. The patient's gastrointestinal function recovered and the pain subsided significantly following treatment with antibiotics. Lyme neuroborreliosis (LNB) often results in palsy, but rarely affects the autonomic nervous system. Three patients have been described with intestinal pseudoobstruction due to acute LNB. However, this is the first described case of intestinal pseudoobstruction due to chronic Lyme neuroborreliosis. LNB must be suspected in patients with intestinal pseudoobstruction, in particular in patients who have been bitten by an ixodes tick and in patients living in an endemic area. PMID- 26130640 TI - Systematic Review With Meta-analysis: Prompt Endoscopy As the Initial Management Strategy for Uninvestigated Dyspepsia in Asi (Aliment Pharmacol Ther 2015;41:239 252). PMID- 26130642 TI - Measurement of Esophagogastric Junction Distensibility May Assist in Selecting Patients for Endoluminal Gastroesophageal Reflux Disease Surgery. PMID- 26130641 TI - TRPC3: A New Target for Therapeutic Strategies in Chronic Pain-DAG-mediated Activation of Non-selective Cation Currents and Chronic Pain (Mol Pain 2014;10:43). PMID- 26130643 TI - Measurement of Esophagogastric Junction Distensibility May Assist in Selecting Patients for Endoluminal Gastroesophageal Reflux Disease Surgery: Author's Reply. PMID- 26130644 TI - The Effect of Stress and Depression on Gastrointestinal Diseases. PMID- 26130645 TI - The Effect of Stress and Depression on Gastrointestinal Diseases: Author's Reply. PMID- 26130646 TI - Effect of micronization on the physicochemical properties of insoluble dietary fiber from citrus (Citrus junos Sieb. ex Tanaka) pomace. AB - The aim of this work was to study the effect of micronization (mechanical and jet grindings) on the physicochemical properties of the insoluble dietary fiber from citrus pomace in comparison with ordinary grinding. The results showed that micronization treatment effectively pulverized the IDF-CP powders to micron scale and significantly increased the soluble dietary fiber content (p < 0.05). Compared with mechanical grinding, jet grinding was more effective in size reduction and resulted in IDF-CP powders with narrower particle size distributions. Micronized IDF-CP powders had smaller particle size, smoother surface, higher fluidity, cation-exchange capacity, and metal cation binding capacity values, but lower water holding capacity, oil holding capacity, and swelling capacity values. These functional properties were significantly dependent on surface area and particle size (D0.5). The present study suggested that micronization treatments could modify functional properties of IDF-CP powders, which promotes their use in food applications. PMID- 26130647 TI - A new feather mite of the genus Dolichodectes (Astigmata: Proctophyllodidae) from Hippolais polyglotta (Passeriformes: Acrocephalidae) in Spain. AB - A new feather mite species, Dolichodectes hispanicus sp. n. (Astigmata: Proctophyllodidae), is described from the Melodious Warbler Hippolais polyglotta (Vieillot) (Passeriformes: Acrocephalidae) in Spain. The new species is closest to the type species of the genus, D. edwardsi (Trouessart, 1885) from the Grear Reed-Warbler Acrocephalus arundinaceus (Linnaeus) (Acrocephalidae). Adults of D. hispanicus differ from those of D. edwardsi by dimensional characteristics, in particular, by having shorter aedeagus that does not extend to the anal suckers in males and shorter hysteronotal shield in females. Tritonymphs of D. hispanicus are much more distinctive and differ from those of D. edwardsi by having the prodorsal shield covering all the prodorsum, the hysteronotal shield occupying about three quarters of the hysterosoma, and idiosomal setae h3 being filiform. The morphological description of the new species is augmented by sequence data from the mitochondrial cytochrome c oxidase subunit I gene fragment (COI). PMID- 26130648 TI - Stem Cell Transfusion Restores Immune Function in Radiation-Induced Lymphopenic C57BL/6 Mice. AB - Radiation-induced lymphopenia (RIL) is associated with treatment of different tumors (lung, colon, pancreas, breast, sarcomas, and glioblastoma). It is a significant clinical problem affecting the survival of cancer patients. The biologic mechanisms leading to RIL are not clearly understood. In this study, we established a mouse model of RIL representing therapeutic clinical regimen for lung cancer. Flow cytometry was used to analyze circulating levels of T and B cells and bone marrow (BM) stem cells. We found that fractionated radiation to the thorax significantly reduced circulating T and B cells as well as BM stem cells. Ex-vivo irradiation of blood and autologous reinjection to mice also significantly induced lymphopenia. Furthermore, we found that mobilization of stem cells from the BM and autologous stem cell transplant rescued RIL in mice. Overall, our results suggest that RIL has not only direct effect on circulating lymphocytes, but also has indirect effect on circulating lymphocytes as well as stem cells in the nonirradiated BM. These results open a new window for investigating the direct and indirect biologic mechanisms leading to RIL, and provide a preclinical basis to test the effect of stem cell transplantation for treatment of RIL in cancer patients. PMID- 26130649 TI - Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein. AB - Eph receptor tyrosine kinases are considered candidate therapeutic targets in cancer, but they can exert opposing effects on cell growth. In the presence of its ligands, Eph receptor EphA2 suppresses signaling by other growth factor receptors, including ErbB, whereas ligand-independent activation of EphA2 augments ErbB signaling. To deploy EphA2-targeting drugs effectively in tumors, the anti-oncogenic ligand-dependent activation state of EphA2 must be discriminated from its oncogenic ligand-independent state. Because the molecular basis for the latter is little understood, we investigated how the activation state of EphA2 can be switched in tumor tissue. We found that ligand-binding domain of EphA2 is cleaved frequently by the membrane metalloproteinase MT1-MMP, a powerful modulator of the pericellular environment in tumor cells. EphA2 immunostaining revealed a significant loss of the N-terminal portion of EphA2 in areas of tumor tissue that expressed MT1-MMP. Moreover, EphA2 phosphorylation patterns that signify ligand-independent activation were observed specifically in these areas of tumor tissue. Mechanistic experiments revealed that processing of EphA2 by MT1-MMP promoted ErbB signaling, anchorage-independent growth, and cell migration. Conversely, expression of a proteolysis-resistant mutant of EphA2 prevented tumorigenesis and metastasis of human tumor xenografts in mice. Overall, our results showed how the proteolytic state of EphA2 in tumors determines its effector function and influences its status as a candidate biomarker for targeted therapy. PMID- 26130650 TI - IL6/JAK1/STAT3 Signaling Blockade in Endometrial Cancer Affects the ALDHhi/CD126+ Stem-like Component and Reduces Tumor Burden. AB - Cancer stem-like cells (CSC) may be critical to maintain the malignant behavior of solid and hematopoietic cancers. Recently, patients with endometrial cancer whose tumors expressed high levels of aldehyde dehydrogenase (ALDH), a detoxifying enzyme characteristic of many progenitor and stem cells, exhibited a relative reduction in survival compared with patients with low levels of ALDH. Given evidence of its role as a CSC marker, we hypothesized that high level of ALDH activity (ALDH(hi)) in a tumor might positively correlate with the presence of stem- and progenitor-like tumor cells in this disease setting. In support of this hypothesis, ALDH could be used to enrich for CSC in endometrial cancer cell lines and primary tumors, as illustrated by the increased tumor-initiating capacity of ALDH(hi) cells in immunodeficient mice. ALDH(hi) cells also exhibited greater clonogenic and organoid-forming capacity compared with ALDH(lo) cells. Notably, the number of ALDH(hi) cells in tumor cell lines and primary tumors inversely correlated with differentiation grade. Expression analysis revealed upregulation of IL6 receptor subunits and signal transducers CD126 and GP130 in ALDH(hi) endometrial cancer cells. Accordingly, targeted inhibition of the IL6 receptor and its downstream effectors JAK1 and STAT3 dramatically reduced tumor cell growth. Overall, our results provide a preclinical rationale to target IL6 or its effector functions as a novel therapeutic option in endometrial cancer. PMID- 26130652 TI - Macroparasites and their communities of the European eel Anguilla anguilla (Linnaeus) in the Czech Republic. AB - This paper summarises the results of parasitological examinations of the European eel Anguilla anguilla (Linnaeus) in the Czech Republic, carried out at the Institute of Parasitology, Czech Academy of Sciences (previously the Czechoslovak Academy of Sciences) within the period of 50 years (1958-2008). Even though this survey is limited to the Czech Republic, it provides extensive data probably incomparable with any other study anywhere regarding the number of eels examined and parasites found. A total of 723 eels was examined from 42 localities that belong to all of the three main river drainage systems in the country, i.e. the Elbe, Danube and Oder river basins. Of the 31 species of adult and larval macroparasites including Monogenea (4 species), Trematoda (3), Cestoda (3), Nematoda (11), Acanthocephala (5), Hirudinea (1), Bivalvia (1), Copepoda (1), Branchiura (1) and Acariformes (1), most of them (30) were recorded from the Elbe River basin. These parasites can be divided into three main groups regarding their host specificity: parasites specific for eels (26%), non-specific adult parasites occurring also in other fishes (61%) and non-specific larvae (13%). The highest number (19) of parasite species was recorded in the Macha Lake fishpond system in northern Bohemia. The parasite communities in eels from the individual localities exhibited large differences in their species composition and diversity depending on local ecological conditions. The parasite fauna of A. anguilla in the Czech Republic is compared with that in other European countries. The nematode Cucullanus egyptae Abdel-Ghaffar, Bashtar, Abdel-Gaber, Morsy, Mehlhorn, Al Quraishy et Mohammed, 2014 is designated as a species inquirenda. PMID- 26130653 TI - Feeling Well and Having Good Numbers: Renal Patients' Encounter With Clinical Uncertainties and the Responsibility to "Live Well". AB - Individuals living with chronic kidney disease (CKD) must be mindful of their diet and exercise, take multiple medications, and deal with other compounding illnesses. We observed renal patients' encounters with health professionals at a renal clinic for tensions and gaps in patients' and health professionals' understandings of "living well" with CKD. We found that the renal patients at the clinic become emotionally invested in the fluctuations in the numbers on their blood work. Narrative practices of health professionals greatly affect how patients emotionally deal with the possibility of dialysis, transplant, death, or aging. Expectations to "live well" can become a moral burden to be a "good" patient. The gaps between the priorities of patients, their caregivers, and health professionals complicate the notion of "living well" with CKD. Trust, rapport and the practice of listening appear to have the greatest impact in addressing these gaps. PMID- 26130651 TI - RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway-Dependent Tumors. AB - Aberrant Shh signaling promotes tumor growth in diverse cancers. The importance of Shh signaling is particularly evident in medulloblastoma and basal cell carcinoma (BCC), where inhibitors targeting the Shh pathway component Smoothened (Smo) show great therapeutic promise. However, the emergence of drug resistance limits long-term efficacy, and the mechanisms of resistance remain poorly understood. Using new medulloblastoma models, we identify two distinct paradigms of resistance to Smo inhibition. Sufu mutations lead to maintenance of the Shh pathway in the presence of Smo inhibitors. Alternatively activation of the RAS MAPK pathway circumvents Shh pathway dependency, drives tumor growth, and enhances metastatic behavior. Strikingly, in BCC patients treated with Smo inhibitor, squamous cell cancers with RAS/MAPK activation emerged from the antecedent BCC tumors. Together, these findings reveal a critical role of the RAS MAPK pathway in drug resistance and tumor evolution of Shh pathway-dependent tumors. PMID- 26130654 TI - Exploring Professional Help-Seeking for Mental Disorders. AB - Only a third of people with mental disorders seek professional help. In this study, we aimed to investigate attitudes toward help-seeking among non-help seekers drawn from a community survey in South London. We conducted qualitative interviews with 24 participants with symptoms of mental disorders. We analyzed data using thematic analysis. Participants' reasons for not seeking professional help included perceiving their problems as normal or unsuitable for professional help, negative expectations of professional help, believing informal strategies were sufficient, fearing being stigmatized for having a mental disorder and help seeking, and self-perceptions of being strong and/or self-reliant. A small number (n = 4) had resolved their problems. Participants with unresolved mental disorders (n = 20) had more chronic stressors, particularly about finances and family relationships, and greater concerns about professional help and stigma than other participants. Potential targets for interventions to encourage help seeking could be focused around stigma about help-seeking as well as the self perception of being strong. PMID- 26130655 TI - Living Well? Strategies Used by Women Living With Metastatic Breast Cancer. AB - Metastatic breast cancer is a disease of changing status-once an imminent death sentence, now a chronic (albeit incurable) disease. Medical intervention advances mean women with metastatic breast cancer now have symptoms alleviated and, potentially, life extended. Living with this disease, however, requires more than a medical approach to symptoms. We were interested to know whether women manage, and if so, how, to "live well" with metastatic cancer. We conducted interviews with 18 women. Women differed in the approaches they used. Most common was the attempt to reestablish a sense of normality in their lives. However, a second group reevaluated and reprioritized their lives; and a third group was restricted in their capacity to live well because of symptoms. The findings provide the foundation for future research exploring normalization of experiences of metastatic cancer, and other chronic illnesses, where people are living with knowledge that they have contracted time. PMID- 26130656 TI - Erratum. AB - Cheek, J., Lipschitz, D. L., Abrams, E. M., Vago, D. R., & Nakamura, Y. (2015). Dynamic reflexivity in action: An armchair walkthrough of a qualitatively driven mixed-method and multiple methods study of mindfulness training in schoolchildren. Qualitative Health Research, 25(6), 751-762. (Original DOI: 10.1177/1049732315582022). PMID- 26130658 TI - A critical analysis of the internal logic in the Life-Space Assessment (LSA) composite score and suggested solutions. AB - BACKGROUND: An individual's ability to live independently is commonly measured in health research interested in identifying risk factors associated with disablement processes. In order to inform clinical practice, population research has attempted to identify the contraction of "lived-space" by using various survey instruments. PROBLEM: Studies assessing habitual movements over the environment with the Life-Space Assessment (LSA) survey instrument should carefully consider how the LSA Composite Score (LSA-CS) is computed. Until now, no publication has carefully delineated the assumptions guiding the internal logic used in the computation of the LSA-CS. CORE ARGUMENT: Because the internal logic of the LSA may need further justification, a non-data-editing scoring algorithm should be considered. SOLUTION: Compute LSA-CS by only using non-edited data. SPECIFIC AIM: Paper first delineates the logic guiding the algorithm used in the formation of the LSA-CS and explains how the scoring creates and changes participant responses when they conflict with its internal logic. An easy-to-use SAS(r) 9.3 program for estimating a Non-Data-Edited LSA-CS (NDE-LSA-CS) is also presented. CONCLUSION: Researchers interested in assessing lived-space should carefully consider if the internal logic of the LSA-CS is warranted. Clinicians should know it is important to understand the strengths and weaknesses of outcome measures used when deciding on whether to apply the results of research to direct clinical practice. PMID- 26130657 TI - Hydrotherapy vs. conventional land-based exercise for improving walking and balance after stroke: a randomized controlled trial. AB - OBJECTIVE: To investigate the effects of hydrotherapy on walking ability and balance in patients with chronic stroke. DESIGN: Single-blind, randomized controlled pilot trial. SETTING: Outpatient rehabilitation clinic at a tertiary neurological hospital in China. SUBJECTS: A total of 28 participants with impairments in walking and controlling balance more than six months post-stroke. INTERVENTION: After baseline evaluations, participants were randomly assigned to a land-based therapy (control group, n = 14) or hydrotherapy (study group, n = 14). Participants underwent individual sessions for four weeks, five days a week, for 45 minutes per session. MAIN MEASURES: After four weeks of rehabilitation, all participants were evaluated by a blinded assessor. Functional assessments included the Functional Reach Test, Berg Balance Scale, 2-minute walk test, and Timed Up and Go Test. RESULTS: After four weeks of treatment, the Berg Balance Scale, functional reach test, 2-minute walk test, and the Timed Up and Go Test scores had improved significantly in each group (P < 0.05). The mean improvement of the functional reach test and 2-minute walk test were significantly higher in the aquatic group than in the control group (P < 0.01). The differences in the mean values of the improvements in the Berg Balance Scale and the Timed Up and Go Test were not statistically significant. CONCLUSION: The results of this study suggest that a relatively short programme (four weeks) of hydrotherapy exercise resulted in a large improvement in a small group (n = 14) of individuals with relatively high balance and walking function following a stroke. PMID- 26130659 TI - Psychometric evaluation of the Posture and Postural Ability Scale for children with cerebral palsy. AB - OBJECTIVE: To evaluate construct validity, internal consistency and inter-rater reliability of the Posture and Postural Ability Scale for children with cerebral palsy. DESIGN: Evaluation of psychometric properties. SETTING: Five child rehabilitation centres in the south of Sweden, in November 2013 to March 2014. SUBJECTS: A total of 29 children with cerebral palsy (15 boys, 14 girls), 6-16 years old, classified at Gross Motor Function Classification System (GMFCS) levels II (n = 10), III (n = 7), IV (n = 6) and V (n = 6). MAIN MEASURES: Three independent raters (two physiotherapists and one orthopaedic surgeon) assessed posture and postural ability of all children in supine, prone, sitting and standing positions, according to the Posture and Postural Ability Scale. Construct validity was evaluated based on averaged values for the raters relative to known-groups in terms of GMFCS levels. Internal consistency was analysed with Cronbach's alpha and corrected Item-Total correlation. Inter-rater reliability was calculated using weighted kappa scores. RESULTS: The Posture and Postural Ability Scale showed construct validity and median values differed between GMFCS levels (p < 0.01). There was a good internal consistency (alpha = 0.95-0.96; item total correlation = 0.55-0.91), and an excellent inter-rater reliability (kappa score = 0.77-0.99). CONCLUSION: The Posture and Postural Ability Scale shows high psychometric properties for children with cerebral palsy, as previously seen when evaluated for adults. It enables detection of postural deficits and asymmetries indicating potential need for support and where it needs to be applied. PMID- 26130660 TI - SInCRe-structural interactome computational resource for Mycobacterium tuberculosis. AB - We have developed an integrated database for Mycobacterium tuberculosis H37Rv (Mtb) that collates information on protein sequences, domain assignments, functional annotation and 3D structural information along with protein-protein and protein-small molecule interactions. SInCRe (Structural Interactome Computational Resource) is developed out of CamBan (Cambridge and Bangalore) collaboration. The motivation for development of this database is to provide an integrated platform to allow easily access and interpretation of data and results obtained by all the groups in CamBan in the field of Mtb informatics. In-house algorithms and databases developed independently by various academic groups in CamBan are used to generate Mtb-specific datasets and are integrated in this database to provide a structural dimension to studies on tuberculosis. The SInCRe database readily provides information on identification of functional domains, genome-scale modelling of structures of Mtb proteins and characterization of the small-molecule binding sites within Mtb. The resource also provides structure based function annotation, information on small-molecule binders including FDA (Food and Drug Administration)-approved drugs, protein-protein interactions (PPIs) and natural compounds that bind to pathogen proteins potentially and result in weakening or elimination of host-pathogen protein-protein interactions. Together they provide prerequisites for identification of off-target binding. PMID- 26130661 TI - Drug-Path: a database for drug-induced pathways. AB - Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. PMID- 26130663 TI - Atrial fibrillation in acute pericarditis: an overblown association. PMID- 26130662 TI - toxoMine: an integrated omics data warehouse for Toxoplasma gondii systems biology research. AB - Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that must monitor for changes in the host environment and respond accordingly; however, it is still not fully known which genetic or epigenetic factors are involved in regulating virulence traits of T. gondii. There are on-going efforts to elucidate the mechanisms regulating the stage transition process via the application of high-throughput epigenomics, genomics and proteomics techniques. Given the range of experimental conditions and the typical yield from such high-throughput techniques, a new challenge arises: how to effectively collect, organize and disseminate the generated data for subsequent data analysis. Here, we describe toxoMine, which provides a powerful interface to support sophisticated integrative exploration of high-throughput experimental data and metadata, providing researchers with a more tractable means toward understanding how genetic and/or epigenetic factors play a coordinated role in determining pathogenicity of T. gondii. As a data warehouse, toxoMine allows integration of high-throughput data sets with public T. gondii data. toxoMine is also able to execute complex queries involving multiple data sets with straightforward user interaction. Furthermore, toxoMine allows users to define their own parameters during the search process that gives users near-limitless search and query capabilities. The interoperability feature also allows users to query and examine data available in other InterMine systems, which would effectively augment the search scope beyond what is available to toxoMine. toxoMine complements the major community database ToxoDB by providing a data warehouse that enables more extensive integrative studies for T. gondii. Given all these factors, we believe it will become an indispensable resource to the greater infectious disease research community. PMID- 26130664 TI - Targeting reperfusion injury in the era of primary percutaneous coronary intervention: hope or hype? AB - Introduction of reperfusion therapy by primary percutaneous coronary intervention (PCI) has resulted in improved outcomes for patients presenting with ST-segment elevation myocardial infarction. Despite the obvious advantages of primary PCI, acute restoration of blood flow paradoxically also jeopardises the myocardium in the first minutes of reperfusion-a phenomenon known as reperfusion injury. Prevention of reperfusion injury may help to improve outcome following primary PCI. This review focuses on the clinical evidence of potential therapeutic cardioprotective methods as adjuvant to primary PCI. Despite overall disappointing, there exists some promising strategies, including ischaemic postconditioning, remote ischaemic conditioning, pharmacological conditioning with focus on adenosine, cyclosporine A, glucose-insulin-potassium, exenatide, atrial natriuretic peptide and metoprolol and cooling. But hitherto no large randomised study has demonstrated any effect on outcome, and ongoing studies that address this issue are underway. Moreover, this review will discuss important clinical predictors associated with reperfusion injury during primary PCI that may interfere with a potential protective effect (pre-PCI thrombolysis in myocardial infarction flow, preinfarction angina, collateral flow, duration of ischaemia and hyperglycaemia). This paper will also provide a short overview of the technical issues related to surrogate endpoints in phase II trials. Based upon these discussions, the paper will provide factors that should be taken into account when designing future clinical studies. PMID- 26130665 TI - Clinical Significance of Peroxisome Proliferator-Activated Receptor gamma and TRAP220 in Patients with Operable Colorectal Cancer. AB - PURPOSE: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARgamma or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). MATERIALS AND METHODS: A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARgamma and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. RESULTS: Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARgamma and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARgamma positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARgamma and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). CONCLUSION: TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARgamma and TRAP220 represents a biomarker for good prognosis in CRC patients. PMID- 26130666 TI - Efficacy of Imatinib in Patients with Platelet-Derived Growth Factor Receptor Alpha-Mutated Gastrointestinal Stromal Tumors. AB - PURPOSE: The incidence of gastrointestinal stromal tumors (GISTs) harboring platelet-derived growth factor receptor alpha (PDGFRA) mutations is low, therefore further investigation of the efficacy of imatinib in this subgroup was needed. MATERIALS AND METHODS: Patients with PDGFRA-mutant GISTs who received imatinib as primary therapy for advanced disease between January 2000 and June 2012 were identified from the GIST registry of Asan Medical Center, Seoul, Korea. RESULTS: KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Exon 18 D842V substitution, non-D842V exon 18 mutations, and exon 12 mutations were detected in nine (50%), four (22%), and five (28%) patients, respectively. Objective response rate differed significantly between patients with the D842V mutation and those with non-D842V mutations (0% [0/5] vs. 71% [5/7], p=0.03). In all patients, median progression-free survival (PFS) and overall survival (OS) was 24.8 months (95% confidence interval [CI], 0.0 to 57.2) and 51.2 months (95% CI, 37.1 to 65.3), respectively. Significantly, poorer PFS was observed for patients with D842V-mutant GISTs than those with non-D842V PDGFRA-mutant GISTs: median 3.8 months (95% CI, 1.4 to 6.3) versus 29.5 months (95% CI, 18.3 to 40.7) (p < 0.001). Patients with the D842V mutation had poorer OS than those with non-D842V PDGFRA mutations: median 25.2 months (95% CI, 12.7 to 37.8) versus 59.8 months (95% CI, 43.0 to 76.5) (p=0.02). CONCLUSION: Imatinib is active against non-D842V PDGFRA-mutant GISTs, whereas GISTs harboring the D842V mutation are primarily resistant to imatinib. PMID- 26130667 TI - Objective Measurement of Cosmetic Outcomes of Breast Conserving Therapy Using BCCT.core. AB - PURPOSE: The purpose of this study is to evaluate objective cosmetic outcomes and factors related to breast-conserving therapy (BCT) using the BCCT.core software. MATERIALS AND METHODS: Fifty-one patients who received BCT with informed consent were evaluated using the BCCT.core software. Patients were divided into two groups based on the BCCT score: excellent or good (n=42) vs. fair or poor (n=9). Analysis of clinical factors was performed to determine factors affecting cosmetic outcomes. RESULTS: The objective cosmetic outcome of BCT measured using the BCCT.core software was excellent in 10% of patients, good in 72%, and fair in 18%. None of the patients were classified as poor outcome. Tumor characteristics, systemic adjuvant therapy (chemotherapy and hormonal therapy), and radiation dose or energy of electron boost did not show correlation with the score measured by the BCCT.core program (p > 0.05). In univariate analysis, maximum dose within the breast (Dmax), width of tangential field, and excised tumor volume were smaller in patients with excellent or good by the BCCT.core compared to those with fair or poor (Dmax, 110.2 +/- 1.5% vs. 111.6 +/- 1.7%, p=0.019; width of tangential field, 8.0 +/- 1.1 cm vs. 8.6 +/- 0.7 cm, p=0.034; excised tumor volume, 64.0 +/- 35.8 cm(3) vs. 95.3 +/- 54.4 cm(3), p=0.067). In multivariate analysis, only Dmax was a significant factor for breast cosmetic outcome with a risk ratio of 1.697 (95% confidence interval, 1.006 to 2.863; p=0.047). CONCLUSION: Objective measurement of cosmetic outcome of BCT using the BCCT.core software was feasible. The cosmetic outcome of BCT may be affected by the maximum dose within the breast. PMID- 26130668 TI - Nucleotide Excision Repair Gene ERCC2 and ERCC5 Variants Increase Risk of Uterine Cervical Cancer. AB - PURPOSE: Defects in the DNA damage repair process can cause genomic instability and play an important role in cervical carcinogenesis. The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer. MATERIALS AND METHODS: Twenty-nine SNPs in four genes in the DNA repair pathway (ERCC2, ERCC5, NBS1, and XRCC1), TP53, and TP53BP1 were genotyped for 478 cervical cancer patients and 922 healthy control subjects, and their effects on cervical carcinogenesis were analyzed. RESULTS: The most significant association was found for rs17655 in ERCC5, with an age-adjusted p-value < 0.0001, for which a strong additive effect of the risk allele C was observed (odds ratio, 2.01 for CC to GG). On the other hand, another significant polymorphism rs454421 in ERCC2 showed a dominant effect (odds ratio, 1.68 for GA+AA to GG) with an age-adjusted p-value of 0.0009. The association of these polymorphisms remained significant regardless of the age of onset. The significant result for rs17655 was also consistent for subgroups of patients defined by histology and human papillomavirus (HPV) types. However, for rs454421, the association was observed only in patients with squamous cell carcinoma and non-HPV 18 type. CONCLUSION: The results of this study show a novel association of cervical cancer and the genes involved in the nucleotide excision pathway in the Korean population. PMID- 26130669 TI - Minor ipsilateral simple limbal epithelial transplantation (mini-SLET) for pterygium treatment. AB - We describe a novel surgical technique for pterygium removal taking advantage of the properties of amniotic membrane and limbal epithelial stem cells. A total of 10 eyes underwent pterygium excision with amniotic membrane coverage of the bare sclera and placement of pieces of limbal epithelium in a linear fashion in the affected limbal area covered by a second amniotic membrane using fibrin glue. After up to 8 months of follow-up, there were no signs of early recurrence or sight-threatening complications. The minor ipsilateral simple limbal epithelial transplantation technique for the treatment of pterygium requires less tissue than the conventional conjunctival autograft, leaving healthy conjunctiva if needed for another procedure in the future and offers the advantages of epithelial stem cells, which in the long term may reduce the rate of recurrence significantly. PMID- 26130670 TI - The prevalence of microcystic macular changes on optical coherence tomography of the macular region in optic nerve atrophy of non-neuritis origin: a prospective study. AB - BACKGROUND: Microcystic macular changes, also called microcystic macular oedema, have recently been reported in patients with multiple sclerosis, particularly after optic neuritis. But it has since emerged that the finding is not specific for optic neuritis. This study was designed to prospectively investigate the prevalence of microcystic perifoveal changes in patients with optic atrophy not due to optic neuritis. METHODS: A prospective, cross-sectional study including 54 patients with a history of optic atrophy and 54 healthy control subjects. Spectral domain optical coherence tomography (SD-OCT) was used to scan the macular area and to measure the peripapillar retinal nerve fibre layer thickness. Scanning laser ophthalmoscopy (SLO) was used for imaging of the macular area. RESULTS: Microcystic macular changes were present in 11/54 patients (20.4%), 17/90 eyes with optic atrophy (18.9%) and absent in the normal eyes of patients with monocular optic atrophy and all healthy control eyes. No correlations were found with the age, duration of optic atrophy or severity of optic atrophy. Besides the known perifoveal (semi) circular abnormal reflexes on SLO imaging, we also noticed a more patchy pattern of low SLO reflections in some patients with optic atrophy. CONCLUSIONS: Microcystic macular changes are a frequent observation in patients with optic atrophy of another cause than optic neuritis. The cause of these abnormalities remains a matter of debate. It is important for clinicians to recognise these macular changes and to realise that the cause may lie remotely away from the macula. PMID- 26130671 TI - Surrogate scleral rim with fibrin glue: a novel technique to expand the pool of donor tissues for Descemet stripping automated endothelial keratoplasty. AB - Descemet stripping automated endothelial keratoplasty is being performed in increasing number of cases each year. An adequate scleral rim on all sides is mandatory for the donor cornea to be mounted on the artificial anterior chamber for microkeratome-assisted dissection. Occasionally, the scleral rim may however be inadequate. The primary cause of inadequate scleral rim is poorly trained technicians in in-situ excision technique. Hence, we devised a novel technique for performing successful microkeratome-assisted dissection in donor corneas with inadequate scleral rim. A surrogate scleral rim was obtained from the donor tissue not fit for optical keratoplasty. It was then glued to the optical grade donor cornea that had an inadequate scleral rim either focally or circumferentially. The combination was then used for a successful microkeratome assisted dissection followed by endothelial keratoplasty. PMID- 26130672 TI - Glaucoma and allergies: 'should I get rid of my cat?'. PMID- 26130673 TI - Radius of curvature changes in spontaneous improvement of foveoschisis in highly myopic eyes. AB - BACKGROUND: Myopic foveoschisis is the splitting of retinal layers overlying staphyloma in highly myopic patients that can lead to vision loss. We assess possible contributing mechanisms to the formation of foveoschisis by examining two cases of spontaneous improvement of myopic foveoschisis and employ a radius of curvature (ROC) measure to track posterior scleral curvature over time. METHODS: A retrospective, non-comparative case series was performed and optical coherence tomography images were analysed. Retinal pigment epithelial layer ROC was calculated from manually segmented images through the posterior scleral curvature apex. RESULTS: Two cases of myopic foveoschisis with foveal detachments in the left eye (OS) were studied. Both patients had high myopia (either <-10 D or >30 mm in axial length). One case occurred in a treatment-naive patient who improved after 4 months of observation. On initial presentation, OS posterior scleral ROC was 12.35 mm and decreased to 12.15 mm at the time of resolution. The other case occurred in a patient who was followed for 7 years, had previously underwent pars plana vitrectomy and removal of epiretinal membrane, experienced recurrence of foveoschisis and then spontaneously improved without further posterior segment surgery. There was an uncomplicated cataract extraction in the interim. Posterior scleral ROC was 4.05 mm on presentation, 4.10 during recurrence, 3.55 mm after cataract extraction and 3.75 mm at resolution. CONCLUSIONS: Spontaneous improvement of myopic foveoschisis may be due to changes in tractional forces from the internal limiting membrane, cortical vitreous or staphyloma or, alternatively, from a delayed or fluctuant recovery course after intervention. PMID- 26130674 TI - Explaining the effects of symptom attribution by carers on help-seeking for individuals living with dementia. AB - This study investigated the effects of carer attributions on help-seeking behaviour for people with dementia using interviews with 84 carers recruited through general practice. Memory loss was the most commonly reported first symptom but psychological and behavioural symptoms were also common at onset. In over a third of individuals help-seeking was delayed for a mean of 25 months (range 6-69, SD 19.3). Help-seeking between those who attributed symptoms to dementia, or to unknown causes, and those who attributed symptoms to personality, ageing, life events or other illnesses was statistically significant ( p < 0.001). No statistically significant associations between help-seeking and patient or carer characteristics were found. There is a need to raise public awareness about the range of symptoms suggestive of dementia. Assumptions that age and other conditions may be the likely cause of an individual's cognitive decline needs to be challenged by practitioners. Attribution of symptoms to characteristics other than dementia delays help-seeking. PMID- 26130675 TI - Prediagnostic serum inflammatory markers in relation to breast cancer risk, severity at diagnosis and survival in breast cancer patients. AB - Inflammation has been linked to cancer but its role in breast cancer is unclear. We investigated common serum markers of inflammation: C-reactive protein (CRP), albumin, haptoglobin and white blood cells (WBC) in relation to breast cancer incidence, severity and survival. A total of 155179 women aged 20 and older without any history of cancer were selected from a large Swedish cohort. Hazard ratios (HRs) for breast cancer were estimated with Cox regression, adjusting for potential confounders. Ordered and binomial logistic regression models were used to assess the associations of serum inflammatory markers with breast cancer severity and oestrogen receptor (ER) positivity at diagnosis, on the other. Cumulative incidence functions by levels of inflammatory markers were assessed for early death from breast cancer and all causes. During a mean follow-up of 18.3 years, 6606 women were diagnosed with breast cancer, of whom 1474 died. A positive association with incident breast cancer was seen for haptoglobin >= 1.4g/l [HR 1.09; 95% confidence interval (CI): 1.00-1.18] compared to lower levels. No association was observed between inflammatory markers and breast cancer severity or ER positivity. Higher haptoglobin was linked to risk of early death from breast cancer (HR: 1.27, 95% CI: 1.02-1.59), whereas higher risk of early death from all causes was additionally found with CRP >= 10mg/l (HR: 1.19, 95% CI: 1.04-1.36) and WBC >= 10*10(9)/l (HR: 1.57, 1.14-2.16). Our findings indicate that prediagnostic serum inflammatory markers were weakly linked to incident breast cancer but corresponded to worse survival after diagnosis. PMID- 26130676 TI - The Workload Curve: Subjective Mental Workload. AB - OBJECTIVE: In this paper I begin looking for evidence of a subjective workload curve. BACKGROUND: Results from subjective mental workload assessments are often interpreted linearly. However, I hypothesized that ratings of subjective mental workload increase nonlinearly with unitary increases in working memory load. METHOD: Two studies were conducted. In the first, the participant provided ratings of the mental difficulty of a series of digit span recall tasks. In the second study, participants provided ratings of mental difficulty associated with recall of visual patterns. The results of the second study were then examined using a mathematical model of working memory. RESULTS: An S curve, predicted a priori, was found in the results of both the digit span and visual pattern studies. A mathematical model showed a tight fit between workload ratings and levels of working memory activation. CONCLUSION: This effort provides good initial evidence for the existence of a workload curve. The results support further study in applied settings and other facets of workload (e.g., temporal workload). APPLICATION: Measures of subjective workload are used across a wide variety of domains and applications. These results bear on their interpretation, particularly as they relate to workload thresholds. PMID- 26130677 TI - Logit-Based Analysis of Drivers' Crossing Behavior at Unsignalized Intersections in China. AB - OBJECTIVE: This study aims to investigate the crossing behavior of straight moving drivers when they encounter other straight-moving drivers at unsignalized intersections in China. BACKGROUND: In China, when two vehicle drivers encounter at an unsignalized intersection, neither driver completely stops his or her vehicle in most cases. Instead, one driver gradually approaches the intersection and dynamically decides to either yield or preempt by gaming with the other vehicle. This process increases the probability of accidents. METHOD: A total of 305 crossing cases were collected at an unsignalized intersection in Kunming City. Motion parameters were extracted from the video detection program designed by our research group. Based on a logistic regression method, we analyzed decision making moment of straight-moving drivers under crossing conditions, established crossing behavior models, and identified the main factors that affected drivers' decisions. In all, 68 cases observed at a separate intersection were used to validate the established models. RESULTS: For crossing processes at unsignalized intersections in China, straight-moving drivers from the right side completed preemptive/yielding decisions at 1.3 s before reaching the crossing point. However, the majority of straight-moving drivers from the left side completed decisions at 1.1 s before reaching the crossing point. The most important parameter that influenced the drivers' decisions was the difference between the speeds of the two vehicles. CONCLUSION: An effective method for preventing traffic conflict between two straight-moving drivers is to control the speeds of the vehicles before they enter the intersection. APPLICATION: This study explores crossing behavior of straight-moving drivers and provides significant insights for controlling driver behavior. PMID- 26130678 TI - A Review of Research on Driving Styles and Road Safety. AB - OBJECTIVE: The aim of this study was to outline a conceptual framework for understanding driving style and, on this basis, review the state-of-the-art research on driving styles in relation to road safety. BACKGROUND: Previous research has indicated a relationship between the driving styles adopted by drivers and their crash involvement. However, a comprehensive literature review of driving style research is lacking. METHOD: A systematic literature search was conducted, including empirical, theoretical, and methodological research, on driving styles related to road safety. RESULTS: A conceptual framework was proposed whereby driving styles are viewed in terms of driving habits established as a result of individual dispositions as well as social norms and cultural values. Moreover, a general scheme for categorizing and operationalizing driving styles was suggested. On this basis, existing literature on driving styles and indicators was reviewed. Links between driving styles and road safety were identified and individual and sociocultural factors influencing driving style were reviewed. CONCLUSION: Existing studies have addressed a wide variety of driving styles, and there is an acute need for a unifying conceptual framework in order to synthesize these results and make useful generalizations. There is a considerable potential for increasing road safety by means of behavior modification. Naturalistic driving observations represent particularly promising approaches to future research on driving styles. APPLICATION: Knowledge about driving styles can be applied in programs for modifying driver behavior and in the context of usage-based insurance. It may also be used as a means for driver identification and for the development of driver assistance systems. PMID- 26130679 TI - The Effect of Maternal Obesity on Pregnancy Outcome in Correlation With Placental Pathology. AB - OBJECTIVES: To investigate the effect of maternal obesity on pregnancy outcome and placental histopathology. STUDY DESIGN: Pregnancy outcome and placental histology from term pregnancies were reviewed. Women were divided according to their prepregnancy body mass index (BMI, kg/m(2)) as normal weight (18-24.9) and obese (>= 30). Pregnancy outcome and placental histology were compared between obese and normal weight women with complicated pregnancies, and with uncomplicated pregnancies, matched by mode of delivery. Placental lesions were classified as lesions of maternal or fetal vascular supply and maternal (MIR) and fetal (FIR) inflammatory responses. RESULTS: Of the 1047 complicated pregnancies analyzed, 615 were with normal weight (BMI 21.7 +/- 1.8) and 221 were obese (BMI 35.2 +/- 4.3). Obesity was associated with higher rates of diabetes and hypertensive disorders (P = .001 for both), birth weight >90th, P < .001, and cesarean delivery, P < .001. Placental weight was higher in obese than in normal weight women, P < .001. No difference was observed in the rate of placental lesions related to maternal or fetal vascular supply and MIR or FIR between the groups. However, higher rate of maternal placental vascular lesions (46.8% vs 28.2%, P = .012) was observed in uncomplicated obese women (n = 62) as compared with healthy normal weight (n = 124) uncomplicated controls. CONCLUSION: Pregnancy outcome is worse without different placental component in obese versus normal weight women, with complicated pregnancies. In uncomplicated pregnancies, more maternal placental vascular supply lesions exist in obese versus normal weight women, suggesting background placental compromise. PMID- 26130681 TI - Childhood Sexual Abuse and Later Alcohol-Related Problems: Investigating the Roles of Revictimization, PTSD, and Drinking Motivations Among College Women. AB - The current study sought to examine whether symptoms of posttraumatic stress disorder (PTSD), adolescent sexual assault (ASA), and drinking motivations (e.g., drinking to regulate emotional experiences) mediate the relationship between a history of childhood sexual abuse (CSA) and subsequent alcohol-related problems among college women. Participants were 579 female students at a Midwestern university. Participants were recruited as part of a larger longitudinal study that investigated risk and resiliency factors related to sexual revictimization. Using a serial mediation model, the current study found that the proposed constructs mediated the relationship between CSA and subsequent alcohol-related problems via two separate paths. In one path, CSA was associated with PTSD, which in turn predicted drinking to regulate emotional experiences, which then was related to alcohol-related problems in adulthood. In the second path, CSA was related to ASA, which in turn predicted drinking to regulate emotional experiences, which then was related to alcohol-related problems in adulthood. These results suggest that individuals with a history of CSA are more likely to experience both revictimization in adolescence and PTSD symptoms in adulthood, which may lead to alcohol-related problems via drinking to regulate emotional experiences. These findings suggest the importance of incorporating skills training in adaptive emotion regulation strategies into treatment for individuals with a history of CSA and ASA. PMID- 26130680 TI - Hypertension in an Animal Model of HELLP Syndrome is Associated With Activation of Endothelin 1. AB - Women with hypertensive forms of pregnancy such as hemolysis-elevated liver enzymes-low platelet syndrome have increased circulating endothelin 1; however, the relationship between hypertension and endothelin 1 has not been studied. Using an animal model, we sought to determine whether there was an increased activation/dysfunction of endothelin 1, the effect of endothelin 1 receptor-A blockade on hypertension and other manifestations of hemolysis, elevated liver enzymes, and low platelets syndrome. On gestational day 12, timed-pregnant rats were infused with soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEndoglin; 4.7 and 7 ug/kg) via mini-osmotic pumps for 8 days. A subset of rats were treated with receptor-A antagonist (ABT-627, 5mg/kg) for 8 days. Rats with hemolysis-elevated liver enzymes-low platelet syndrome had significantly increased hypertension (P = .0001), circulating endothelin 1 (P = .03), and a significant 3.3- and 7.2-fold increase in preproendothelin messenger RNA (mRNA) expression in the placenta and liver (P = .01 and .04). Urinary protein:creatinine ratio was significantly increased in these animals (P = .0007), and circulating factors from these rats stimulated a significant increase in endothelial cell secretion of endothelin 1 (P = .001) in an in vitro assay. Blockade of the endothelin 1 receptor A significantly decreased hypertension (P = .001), circulating endothelin 1, and interleukin 17 (P = .004 and .003), placental preproendothelin mRNA expression (P = .016), and urinary protein:creatinine ratio (P = .007) in rats with hemolysis-elevated liver enzymes low platelet syndrome. Blockade of the endothelin 1 receptor A significantly decreased hemolysis (P = .009), liver enzymes (P = .011), and significantly increased platelet levels (P = .03) and decreased circulating CD4+ and CD8+ T lymphocytes (P = .0004 and .0001) in rats infused with sFlt-1 and sEndoglin. These data support the hypothesis that endothelin 1 activation has a critical role in pathophysiology of as hemolysis-elevated liver enzymes-low platelet syndrome. PMID- 26130682 TI - Looking for Blame: Rape Myth Acceptance and Attention to Victim and Perpetrator. AB - In two studies, the authors examined the influence of rape myth acceptance (RMA) on participants' attention toward the potential victim versus perpetrator in a rape case. In Study 1 ( N = 90), participants selected information that focused on either the male defendant or the female victim. With increasing RMA, participants preferred information that focused on the victim rather than the defendant. In Study 2 ( N = 41), participants viewed photographs depicting both victim and defendant while their eye movements were recorded. With increasing RMA, participants spent less time inspecting the defendant relative to the victim. In both studies, higher RMA predicted stronger anti-victim and pro defendant judgments, replicating previous research. Taken together, these results support the assumption that RMA guides participants' attention, leading to a focus on the alleged rape victim and away from the alleged perpetrator. Implications of the current research and future directions are discussed. PMID- 26130683 TI - Torn: Social Expectations Concerning Forgiveness Among Women Who Have Experienced Intrafamilial Child Sexual Abuse. AB - The authors examine how women who experienced intrafamilial child sexual abuse (IFCSA) perceive social expectations of society toward forgiveness, how they incorporate IFCSA and reconstruct their life stories in relation to these expectations, and the costs and gains from such reconstructions. This is part of a larger study on the phenomenology of forgiveness for IFCSA among grown women. Twenty Jewish Israeli women who had experienced IFCSA were interviewed in depth. Interviews were tape-recorded and transcribed verbatim. Data analyses lead to four types of social expectations: forgiveness by forgetting, avenging, family preservation through forgiveness, and satisfying the voyeuristic needs of society, which has limited interest in forgiveness. These contradictory expectations are discussed in light of the cultural context and the experience of the women interviewed. Implications for practice are suggested. PMID- 26130684 TI - The Relationship Between Emotion Regulation, Executive Functioning, and Aggressive Behaviors. AB - Emotion regulation deficits and executive functioning deficits have independently been shown to increase vulnerability toward engaging in aggressive behaviors. The effects of these risk factors, however, have not been evaluated in relation to one another. This study evaluated the degree to which each was associated with aggressive behaviors in a sample of 168 undergraduate students. Executive functioning (cognitive inhibition and mental flexibility) was assessed with a Stroop-like neuropsychological task. Emotion regulation and aggressive behaviors were assessed via self-report inventories. Results showed main effects for both emotion regulation and executive functioning, as well as a significant interaction, indicating that those who scored lowest in both domains reported engaging in aggressive behaviors the most frequently. When different types of aggression were examined, this interaction was only significant for acts of physical aggression, not for acts of verbal aggression. Therefore, for physical aggression, emotion regulation and executive functioning exerted a moderating effect on one another. The implications are that, at least for acts of physical aggression, relatively strong capabilities in either domain may buffer against tendencies to engage in aggressive behaviors. Thus, both emotion regulation skills and executive functioning abilities may be valuable targets for interventions aiming to reduce aggressive behaviors. PMID- 26130685 TI - Family Polyvictimization and Elevated Levels of Addiction and Psychopathology Among Parents in a Chinese Household Sample. AB - When studying the co-occurring victimization within a family, current literature often focuses on individual violence and fails to cover more than two forms of violence. This study fills the research gap by using families, instead of individuals, as units and investigating the prevalence of family polyvictimization. Family polyvictimization is defined as the co-occurrence of child victimization, intimate partner violence (IPV) between parents, and elder abuse within a family. This study analyzed a set of data from 7,466 households, with at least a child under 18 years of age, in six regions in China collected during 2009 and 2010. Descriptive analyses and ordinal logistic regressions were performed to explore the prevalence of family polyvictimization, as well as its associations with parents' addictive behaviors and negative health factors. The lifetime prevalence and the past-year prevalence of family polyvictimization was 2.53% and 1.09%, respectively. Parents from a polyvictimized family were more likely to report addictive behaviors, and to show poorer mental health and more posttraumatic stress disorder (PTSD) and depressive symptoms than those who were less exposed to violence. Findings show the importance of the whole-family approach to screening multiple types of violence within a family when one type is detected, as well as the potential usefulness of identifying at-risk families among parents with addictive behaviors and poor mental health. PMID- 26130686 TI - Therapeutic Progression in Abused Women Following a Drug-Addiction Treatment Program. AB - This study explored the prevalence of victims of abuse and the therapeutic progression among women who sought treatment for drug addiction. A sample of 180 addicted Spanish women was assessed. Information was collected on the patients' lifetime history of abuse (psychological, physical, and/or sexual), socio demographic factors, consumption variables, and psychological symptoms. Of the total sample, 74.4% ( n = 134) of the addicted women had been victims of abuse. Psychological abuse affected 66.1% ( n = 119) of the patients, followed by physical abuse (51.7%; n = 93) and sexual abuse (31.7%; n = 57). Compared with patients who had not been abused, the addicted women with histories of victimization scored significantly higher on several European version of the Addiction Severity Index (EuropASI) and psychological variables. Specifically, physical abuse and sexual abuse were related to higher levels of severity of addiction. Regarding therapeutic progression, the highest rate of dropout was observed among victims of sexual abuse (63.5%; n = 33), followed by victims of physical abuse (48.9%; n = 23). Multivariate analysis showed that medical and family areas of the EuropASI, as well as violence problems and suicide ideation, were the main variables related to physical and/or sexual abuse. Moreover, women without abuse and with fewer family problems presented the higher probability of treatment completion. The implications of these results for further research and clinical practice are discussed. PMID- 26130687 TI - Unwanted Behaviors and Nuisance Behaviors Among Neighbors in a Belgian Community Sample. AB - Unwanted behaviors between (ex-)intimates have been extensively studied, while those behaviors within other contexts such as neighbors have received much less scientific consideration. Research indicates that residents are likely to encounter problem behaviors from their neighbors. Besides the lack of clarity in the conceptualization of problem behaviors among neighbors, little is known on which types of behaviors characterize neighbor problems. In this study, the occurrence of two types of problem behaviors encountered by neighbors was explored within a Belgian community sample: unwanted behaviors such as threats and neighbor nuisance issues such as noise nuisance. By clearly distinguishing those two types of behaviors, this study aimed at contributing to the conceptualization of neighbor problems. Next, the coping strategies used to deal with the neighbor problems were investigated. Our results indicated that unwanted behaviors were more frequently encountered by residents compared with nuisance problems. Four out of 10 respondents reported both unwanted pursuit behavior and nuisance problems. It was especially unlikely to encounter nuisance problems in isolation of unwanted pursuit behaviors. While different coping styles (avoiding the neighbor, confronting the neighbor, and enlisting help from others) were equally used by the stalked participants, none of them was perceived as being more effective in reducing the stalking behaviors. Strikingly, despite being aware of specialized help services such as community mediation services, only a very small subgroup enlisted this kind of professional help. PMID- 26130688 TI - Alcohol Expectancy, Drinking Behavior, and Sexual Victimization Among Female and Male College Students. AB - College students have high rates of heavy drinking, and this dangerous behavior is strongly linked to sexual victimization. Although research has examined risk factors for sexual assault, few studies have simultaneously studied the various pathways through which risks may affect sexual assault and how these pathways may be uniquely different among females and males. As such, the current study uses path analyses to examine whether alcohol expectancies mediate the relationship between social factors (e.g., hooking up, amount friends drink) and drinking behavior and experiencing sexual victimization, and whether drinking behavior mediates the relationship between alcohol expectancies and sexual victimization among a college sample of 704 males and females from a large Midwestern university. For both females and males, sexual victimization was positively associated with child sexual abuse, hooking up more often, and heavier drinking, whereas greater alcohol expectancies were associated with sexual victimization only for females. Several mediating pathways were found for both females and males. Gender comparisons revealed that some of the pathways to sexual victimization such as hooking up, amount friends drink, and housing type operated differently for females and males. PMID- 26130689 TI - Morphological distribution of cervical and corpus uteri cancer from Cancer Incidence in Five Continents Vol. X. PMID- 26130690 TI - The potential risks of probiotics among HIV-infected persons: Bacteraemia due to Lactobacillus acidophilus and review of the literature. AB - Lactobacillus sp. are commensal organisms that are increasingly reported to cause invasive infections among immunosuppressed persons. However, few data exist regarding the occurrence and risk factors of these infections among HIV-infected persons. Further, the safety of products that contain lactobacilli (e.g. probiotics) in certain populations, including those with HIV/AIDS, is unclear. We report a case of Lactobacillus acidophilus bacteraemia in a patient with AIDS temporally related to excessive consumption of probiotic-enriched yogurt, and provide a comprehensive review of the literature of Lactobacillus sp. infections among HIV-infected persons. PMID- 26130691 TI - High rates of cervical cancer among HIV-infected women at a referral hospital in Malawi. AB - Cervical cancer is the most common cancer among women in Malawi. National guidelines recommend screening women aged 30-45 years every five years; however, no specific recommendations exist for women with HIV. We aimed to assess the frequency of high-grade dysplasia (CIN 2 or CIN3) and cervical cancer among women in central Malawi and to examine associations with CIN2+ (CIN2/3 or cancer). We extracted cervical Pap smear, biopsy, loop electrosurgical excision procedure and uterine specimen reports from a hospital pathology database from November 2012 to November 2013. We used logistic regression to estimate associations with CIN2+. We reviewed specimens from 824 women; we excluded 194 with unknown HIV status, leaving 630 in the analytic sample. Twelve percent had high-grade dysplasia and 109 women (17%) had cancer. Twenty-five percent of high-grade dysplasia cases and 35% of cancers occurred among women outside recommended screening ages. The odds of having CIN2+ were 6.55 times (95% CI 4.44-9.67) greater for HIV+ women. High grade dysplasia and cervical cancer are very common among Malawian women, especially HIV+ women. HIV infection was strongly associated with CIN2+. Expanding screening to women not covered by current guidelines could avert a substantial proportion of cervical cancer cases in Malawi. PMID- 26130692 TI - PABPN1 suppresses TDP-43 toxicity in ALS disease models. AB - TAR DNA-binding protein 43 (TDP-43) is a major disease protein in amyotrophic lateral sclerosis (ALS) and related neurodegenerative diseases. Both the cytoplasmic accumulation of toxic ubiquitinated and hyperphosphorylated TDP-43 fragments and the loss of normal TDP-43 from the nucleus may contribute to the disease progression by impairing normal RNA and protein homeostasis. Therefore, both the removal of pathological protein and the rescue of TDP-43 mislocalization may be critical for halting or reversing TDP-43 proteinopathies. Here, we report poly(A)-binding protein nuclear 1 (PABPN1) as a novel TDP-43 interaction partner that acts as a potent suppressor of TDP-43 toxicity. Overexpression of full length PABPN1 but not a truncated version lacking the nuclear localization signal protects from pathogenic TDP-43-mediated toxicity, promotes the degradation of pathological TDP-43 and restores normal solubility and nuclear localization of endogenous TDP-43. Reduced levels of PABPN1 enhances the phenotypes in several cell culture and Drosophila models of ALS and results in the cytoplasmic mislocalization of TDP-43. Moreover, PABPN1 rescues the dysregulated stress granule (SG) dynamics and facilitates the removal of persistent SGs in TDP-43 mediated disease conditions. These findings demonstrate a role for PABPN1 in rescuing several cytopathological features of TDP-43 proteinopathy by increasing the turnover of pathologic proteins. PMID- 26130694 TI - CNVs in neuropsychiatric disorders. AB - Over the last few years at least 11 copy number variations (CNVs) have been shown convincingly to increase risk to developing schizophrenia: deletions at 1q21.1, NRXN1, 3q29, 15q11.2, 15q13.3 and 22q11.2, and duplications at 1q21.1, 7q11.23, 15q11.2-q13.1, 16p13.1 and proximal 16p11.2. They are very rare, found cumulatively in 2.4% of patients with schizophrenia and in only 0.5% of controls. They all increase risk for other neurodevelopmental disorders, such as developmental delay and autism spectrum disorders, where they are found at higher rates (3.3%). Their involvement in bipolar affective disorder is much less prominent. All of them affect multiple genes (apart from NRXN1) and cause substantial increases in risk to develop schizophrenia (odds ratios of 2 to over 50). Their penetrance for any neurodevelopmental disorder is high, from ~10% to nearly 100%. Carriers of these CNVs display cognitive deficits, even when free of neuropsychiatric disorders. PMID- 26130693 TI - Recognizable cerebellar dysplasia associated with mutations in multiple tubulin genes. AB - Mutations in alpha- and beta-tubulins are increasingly recognized as a major cause of malformations of cortical development (MCD), typically lissencephaly, pachygyria and polymicrogyria; however, sequencing tubulin genes in large cohorts of MCD patients has detected tubulin mutations in only 1-13%. We identified patients with a highly characteristic cerebellar dysplasia but without lissencephaly, pachygyria and polymicrogyria typically associated with tubulin mutations. Remarkably, in seven of nine patients (78%), targeted sequencing revealed mutations in three different tubulin genes (TUBA1A, TUBB2B and TUBB3), occurring de novo or inherited from a mosaic parent. Careful re-review of the cortical phenotype on brain imaging revealed only an irregular pattern of gyri and sulci, for which we propose the term tubulinopathy-related dysgyria. Basal ganglia (100%) and brainstem dysplasia (80%) were common features. On the basis of in silico structural predictions, the mutations affect amino acids in diverse regions of the alpha-/beta-tubulin heterodimer, including the nucleotide binding pocket. Cell-based assays of tubulin dynamics reveal various effects of the mutations on incorporation into microtubules: TUBB3 p.Glu288Lys and p.Pro357Leu do not incorporate into microtubules at all, whereas TUBB2B p.Gly13Ala shows reduced incorporation and TUBA1A p.Arg214His incorporates fully, but at a slower rate than wild-type. The broad range of effects on microtubule incorporation is at odds with the highly stereotypical clinical phenotype, supporting differential roles for the three tubulin genes involved. Identifying this highly characteristic phenotype is important due to the low recurrence risk compared with the other (recessive) cerebellar dysplasias and the apparent lack of non neurological medical issues. PMID- 26130696 TI - Ubersense Coach app for sport medicine? Slow motion video analysis (Mobile App User Guide). PMID- 26130697 TI - Prospective comparison of running injuries between shod and barefoot runners. AB - BACKGROUND: Advocates of barefoot running suggest that it is more natural and may be a way to minimise injury risk. In contrast, opponents believe shoes are needed to adequately cushion and support the foot. However, to date, there have been no prospective studies of injury patterns in barefoot and shod runners. The purpose of this study was to compare the incidence and rate of injuries between shod and barefoot runners. METHODS: A prospective survey was conducted over the course of a year among 201 (107 barefoot and 94 shod) adult runners. Information regarding injuries and mileage was logged monthly using a custom, web-based database program. The number of injured runners, number of injuries per runner and injury rates were compared between habitual barefoot and habitual shod runners. Both musculoskeletal and plantar surface injuries were assessed. RESULTS: Statistically fewer overall, diagnosed, musculoskeletal injuries/runner were noted in the barefoot group. However, injury rates were not statistically different between groups due to significantly less mileage run in the barefoot group. As expected, barefoot runners sustained a statistically greater number of injuries to the plantar surface of the foot. The descriptive analysis suggests a greater number of calf injuries, but lower number of knee and hip injuries in the barefoot group. Additionally barefoot runners reported less plantar fasciitis than the shod group. CONCLUSIONS: Barefoot running is associated with fewer overall musculoskeletal injuries/runner, but similar injury rates. A larger scale cohort is needed to more accurately assess differences in individual injuries between these two groups. PMID- 26130698 TI - Stabbed in the back: catalysts for a paradigm shift in back pain care. PMID- 26130699 TI - What is femoroacetabular impingement? PMID- 26130695 TI - FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor. AB - Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of function variant in FANCM is a risk factor for familial breast cancer. PMID- 26130700 TI - Athletic groin pain: a systematic review and meta-analysis of surgical versus physical therapy rehabilitation outcomes. AB - BACKGROUND: Athletic groin pain (AGP) is an encompassing term for the multitude of chronic conditions presenting as pain in the inguinal region. The purpose of this review was to compare the return to play rates (RTPrate) and return to play times (RTPtime) between surgical and rehabilitation interventions in the treatment of AGP. METHODS: A systematic review of English language peer review journals was carried out between 1980 to June 2013 using PubMed, Embase, CINHAL and Google Scholar searching for all papers relating to AGP (and its various pseudonyms) and all surgical and rehabilitative interventions which reported RTPrate and/or RTPtime. AGP literature has been subdivided by many eponymous diagnoses but anatomical diagnostic groupings of (1) abdominal wall, (2) adductor and (3) pubic related pain were used in this review. Meta-analysis was then carried out on the data to compare results between the surgical and rehabilitation groups. RESULTS: Fifty-six papers out of the 561 discovered in the initial search were included in the review with 3332 athletes included. Evidence was mostly level IV. Using the Black and Downs checklist we found poor study quality overall with a high risk of bias especially among surgical studies. The results showed comparable RTPrate between surgical and rehabilitative interventions within the three diagnostic groups. Rehabilitation had significantly quicker RTPtime for pubic related groin pain compared to surgery (10.5 weeks and 23.1 weeks respectively). The abdominal group had the fastest return of the three groups for the rehabilitation and surgery. CONCLUSIONS: The review suggested better outcomes with rehabilitation for pubic-related groin pain with no difference between the adductor and abdominal groups. The review highlighted the poor quality and risk of bias in the literature making accurate comparison difficult. PMID- 26130701 TI - IFN-lambda is able to augment TLR-mediated activation and subsequent function of primary human B cells. AB - During the past decade, increased emphasis has been placed on finding alternatives to IFN-alpha-based therapies. One such alternative, IFN-lambda, has shown therapeutic promise in a variety of diseases, but research of this family of cytokines has been primarily focused on their antiviral activities. The goal of the present study was to investigate the role of IFN-lambda in the regulation and modulation of B cell function. We show that, similar to IFN-alpha, IFN lambda1 is able to augment TLR-mediated B cell activation, partially attributed to an upregulation of TLR7 expression, and that both naive and memory B cells express the limiting type III IFN receptor component, IFN-lambdaR1. Furthermore, this IFN-lambda-enhanced B cell activation resulted in increased cytokine and Ig production during TLR7 challenge, most prominently after the addition of helper T cell signals. Ultimately, these elevated cytokine and Ig levels could be partially attributed to the increase in proliferation of TLR7-challenged B cells by both type I and type III IFNs. These findings demonstrate the ability of IFN lambda to boost humoral immunity, an important attribute to consider for further studies on immunity to pathogens, vaccine development, and ongoing advancement of therapeutic strategies aimed at replacing IFN-alpha-based treatments with IFN lambda. PMID- 26130702 TI - Emerging functions of serum amyloid A in inflammation. AB - SAA is a major acute-phase protein produced in large quantity during APR. The rise of SAA concentration in blood circulation during APR has been a clinical marker for active inflammation. In the past decade, research has been conducted to determine whether SAA plays an active role during inflammation and if so, how it influences the course of inflammation. These efforts have led to the discovery of cytokine-like activities of rhSAA, which is commercially available and widely used in most of the published studies. SAA activates multiple receptors, including the FPR2, the TLRs TLR2 and TLR4, the scavenger receptor SR-BI, and the ATP receptor P2X7. More recent studies have shown that SAA not only activates transcription factors, such as NF-kappaB, but also plays a role in epigenetic regulation through a MyD88-IRF4-Jmjd3 pathway. It is postulated that the activation of these pathways leads to induced expression of proinflammatory factors and a subset of proteins expressed by the M2 macrophages. These functional properties set SAA apart from well-characterized inflammatory factors, such as LPS and TNF-alpha, suggesting that it may play a homeostatic role during the course of inflammation. Ongoing and future studies are directed to addressing unresolved issues, including the difference between rSAA and native SAA isoforms and the exact functions of SAA in physiologic and pathologic settings. PMID- 26130703 TI - Evolution of Respiratory Proteins across the Pancrustacea. AB - Respiratory proteins enhance the capacity of the blood for oxygen transport and support intracellular storage and delivery of oxygen. Hemocyanin and hemoglobin are the respiratory proteins that occur in the Pancrustacea. The copper containing hemocyanins evolved from phenoloxidases in the stem lineage of arthropods. For a long time, hemocyanins had only been known from the malacostracan crustaceans but recent studies identified hemocyanin also in Remipedia, Ostracoda, and Branchiura. Hemoglobins are common in the Branchiopoda but have also been sporadically found in other crustacean classes (Malacostraca, Copepoda, Thecostraca). Respiratory proteins had long been considered unnecessary in the hexapods because of the tracheal system. Only chironomids, some backswimmers, and the horse botfly, which all live under hypoxic conditions, were known exceptions and possess hemoglobins. However, recent data suggest that hemocyanins occur in most ametabolous and hemimetabolous insects. Phylogenetic analysis showed the hemocyanins of insects and Remipedia to be similar, suggesting a close relationship of these taxa. Hemocyanin has been lost in dragonflies, mayflies, and Eumetabola (Hemiptera + Holometabola). In cockroaches and grasshoppers, hemocyanin expression is restricted to the developing embryo while in adults oxygen is supplied solely by the tracheal system. This pattern suggests that hemocyanin was the oxygen-transport protein in the hemolymph of the last common ancestor of the pancrustaceans. The loss was probably associated with miniaturization, a period of restricted availability of oxygen, a change in life style, or morphological changes. Once lost, hemocyanin was not regained. Some pancrustaceans also possess cellular globin genes with uncertain functions, which are expressed at low levels. When a respiratory protein was again required, hemoglobins evolved several times independently from cellular globins. PMID- 26130704 TI - The tick Ixodida: an unusual foreign body in the ear. AB - We report a patient with a hard tick in her left ear, adherent to the tympanic membrane. PMID- 26130705 TI - Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. AB - We studied adults with acute myeloid leukemia (AML) after haploidentical (n = 192) and 8/8 HLA-matched unrelated donor (n = 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens. In the myeloablative setting, day 30 neutrophil recovery was lower after haploidentical compared with matched unrelated donor transplants (90% vs 97%, P = .02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96% (P = .25). In the myeloablative setting, 3-month acute grade 2-4 (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) were lower after haploidentical compared with matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% vs 28% (P = .05) and 34% vs 52% (P = .002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI, 36-54) and 50% (95% CI, 47-53) after haploidentical and matched unrelated donor transplants (P = .38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI, 35-56) and 44% (95% CI, 0.40-47) (P = .71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. PMID- 26130706 TI - Acute GVHD results in a severe DC defect that prevents T-cell priming and leads to fulminant cytomegalovirus disease in mice. AB - Viral infection is a common, life-threatening complication after allogeneic bone marrow transplantation (BMT), particularly in the presence of graft-versus-host disease (GVHD). Using cytomegalovirus (CMV) as the prototypic pathogen, we have delineated the mechanisms responsible for the inability to mount protective antiviral responses in this setting. Although CMV infection was self-limiting after syngeneic BMT, in the presence of GVHD after allogeneic BMT, CMV induced a striking cytopathy resulting in universal mortality in conjunction with a fulminant necrotizing hepatitis. Critically, GVHD induced a profound dendritic cell (DC) defect that led to a failure in the generation of CMV-specific CD8(+) T cell responses. This was accompanied by a defect in antiviral CD8(+) T cells. In combination, these defects dramatically limited antiviral T-cell responses. The transfer of virus-specific cells circumvented the DC defects and provided protective immunity, despite concurrent GVHD. These data demonstrate the importance of avoiding GVHD when reconstructing antiviral immunity after BMT, and highlight the mechanisms by which the adoptive transfer of virus-specific T cells overcome the endogenous defects in priming invoked by GVHD. PMID- 26130707 TI - Destabilization of microRNAs in human cells by 3' deadenylation mediated by PARN and CUGBP1. AB - MicroRNA-122 (miR-122), which is expressed at high levels in hepatocytes, is selectively stabilized by 3'-adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Here, we report that poly(A)-specific ribonuclease (PARN) is responsible for the deadenylation and destabilization of miR-122. The 3' oligoadenylated variant of miR-122 was detected in Huh7 cells when PARN was down regulated. In addition, both the steady-state level and stability of miR-122 were increased in PARN knockdown cells. We also demonstrate that CUG-binding protein 1 (CUGBP1) specifically interacts with miR-122 and other UG-rich miRNAs, and promotes their destabilization. Overexpression of CUGBP1 or PARN in Huh7 cells reduced the steady-state levels of these miRNAs. Because CUGBP1 interacts directly with PARN, we hypothesized that it specifically recruits PARN to miR 122. In fact, CUGBP1 enhanced PARN-mediated deadenylation and degradation of miR 122 in a dose-dependent manner in vitro. These results indicate that the cellular level of miR-122 is determined by the balance between the opposing effects of GLD 2 and PARN/CUGBP1 on the metabolism of its 3'-terminus. PMID- 26130708 TI - Biological chromodynamics: a general method for measuring protein occupancy across the genome by calibrating ChIP-seq. AB - Sequencing DNA fragments associated with proteins following in vivo cross-linking with formaldehyde (known as ChIP-seq) has been used extensively to describe the distribution of proteins across genomes. It is not widely appreciated that this method merely estimates a protein's distribution and cannot reveal changes in occupancy between samples. To do this, we tagged with the same epitope orthologous proteins in Saccharomyces cerevisiae and Candida glabrata, whose sequences have diverged to a degree that most DNA fragments longer than 50 bp are unique to just one species. By mixing defined numbers of C. glabrata cells (the calibration genome) with S. cerevisiae samples (the experimental genomes) prior to chromatin fragmentation and immunoprecipitation, it is possible to derive a quantitative measure of occupancy (the occupancy ratio - OR) that enables a comparison of occupancies not only within but also between genomes. We demonstrate for the first time that this 'internal standard' calibration method satisfies the sine qua non for quantifying ChIP-seq profiles, namely linearity over a wide range. Crucially, by employing functional tagged proteins, our calibration process describes a method that distinguishes genuine association within ChIP-seq profiles from background noise. Our method is applicable to any protein, not merely highly conserved ones, and obviates the need for the time consuming, expensive, and technically demanding quantification of ChIP using qPCR, which can only be performed on individual loci. As we demonstrate for the first time in this paper, calibrated ChIP-seq represents a major step towards documenting the quantitative distributions of proteins along chromosomes in different cell states, which we term biological chromodynamics. PMID- 26130709 TI - A nested parallel experiment demonstrates differences in intensity-dependence between RNA-seq and microarrays. AB - Understanding the differences between microarray and RNA-Seq technologies for measuring gene expression is necessary for informed design of experiments and choice of data analysis methods. Previous comparisons have come to sometimes contradictory conclusions, which we suggest result from a lack of attention to the intensity-dependent nature of variation generated by the technologies. To examine this trend, we carried out a parallel nested experiment performed simultaneously on the two technologies that systematically split variation into four stages (treatment, biological variation, library preparation and chip/lane noise), allowing a separation and comparison of the sources of variation in a well-controlled cellular system, Saccharomyces cerevisiae. With this novel dataset, we demonstrate that power and accuracy are more dependent on per-gene read depth in RNA-Seq than they are on fluorescence intensity in microarrays. However, we carried out quantitative PCR validations which indicate that microarrays may demonstrate greater systematic bias in low-intensity genes than in RNA-seq. PMID- 26130710 TI - The missing indels: an estimate of indel variation in a human genome and analysis of factors that impede detection. AB - With the development of High-Throughput Sequencing (HTS) thousands of human genomes have now been sequenced. Whenever different studies analyze the same genome they usually agree on the amount of single-nucleotide polymorphisms, but differ dramatically on the number of insertion and deletion variants (indels). Furthermore, there is evidence that indels are often severely under-reported. In this manuscript we derive the total number of indel variants in a human genome by combining data from different sequencing technologies, while assessing the indel detection accuracy. Our estimate of approximately 1 million indels in a Yoruban genome is much higher than the results reported in several recent HTS studies. We identify two key sources of difficulties in indel detection: the insufficient coverage, read length or alignment quality; and the presence of repeats, including short interspersed elements and homopolymers/dimers. We quantify the effect of these factors on indel detection. The quality of sequencing data plays a major role in improving indel detection by HTS methods. However, many indels exist in long homopolymers and repeats, where their detection is severely impeded. The true number of indel events is likely even higher than our current estimates, and new techniques and technologies will be required to detect them. PMID- 26130711 TI - Two separable functions of Ctp1 in the early steps of meiotic DNA double-strand break repair. AB - Meiotic programmed DNA double-strand break (DSB) repair is essential for crossing over and viable gamete formation and requires removal of Spo11-oligonucleotide complexes from 5' ends (clipping) and their resection to generate invasive 3'-end single-stranded DNA (resection). Ctp1 (Com1, Sae2, CtIP homolog) acting with the Mre11-Rad50-Nbs1 (MRN) complex is required in both steps. We isolated multiple S. pombe ctp1 mutants deficient in clipping but proficient in resection during meiosis. Remarkably, all of the mutations clustered in or near the conserved CxxC or RHR motif in the C-terminal portion. The mutants tested, like ctp1Delta, were clipping-deficient by both genetic and physical assays-. But, unlike ctp1Delta, these mutants were recombination-proficient for Rec12 (Spo11 homolog)-independent break-repair and resection-proficient by physical assay. We conclude that the intracellular Ctp1 C-terminal portion is essential for clipping, while the N terminal portion is sufficient for DSB end-resection. This conclusion agrees with purified human CtIP resection and endonuclease activities being independent. Our mutants provide intracellular evidence for separable functions of Ctp1. Some mutations truncate Ctp1 in the same region as one of the CtIP mutations linked to the Seckel and Jawad severe developmental syndromes, suggesting that these syndromes are caused by a lack of clipping at DSB ends that require repair. PMID- 26130712 TI - Linking two DNA duplexes with a rigid linker for DNA nanotechnology. AB - DNA has recently emerged as a promising material for the construction of nanosized architectures. Chemically modified DNA has been suggested to be an important component of such architectural building blocks. We have designed and synthesized a novel H-shaped DNA oligonucleotide dimer that is cross-linked with a structurally rigid linker composed of phenylene and ethynylene groups. A rotatable DNA unit was constructed through the self-assembly of this H-shaped DNA component and two complementary DNA oligonucleotides. In addition to the rotatable unit, a locked DNA unit containing two H-shaped DNA components was also constructed. As an example of an extended locked structure, a hexagonal DNA origami dimer and oligomer were constructed by using H-shaped DNA as linkers. PMID- 26130713 TI - MicroRNA-29b/Tet1 regulatory axis epigenetically modulates mesendoderm differentiation in mouse embryonic stem cells. AB - Ten eleven translocation (Tet) family-mediated DNA oxidation on 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) represents a novel epigenetic modification that regulates dynamic gene expression during embryonic stem cells (ESCs) differentiation. Through the role of Tet on 5hmC regulation in stem cell development is relatively defined, how the Tet family is regulated and impacts on ESCs lineage development remains elusive. In this study, we show non-coding RNA regulation on Tet family may contribute to epigenetic regulation during ESCs differentiation, which is suggested by microRNA-29b (miR-29b) binding sites on the Tet1 3' untranslated region (3' UTR). We demonstrate miR-29b increases sharply after embyoid body (EB) formation, which causes Tet1 repression and reduction of cellular 5hmC level during ESCs differentiation. Importantly, we show this miR-29b/Tet1 regulatory axis promotes the mesendoderm lineage formation both in vitro and in vivo by inducing the Nodal signaling pathway and repressing the key target of the active demethylation pathway, Tdg. Taken together, our findings underscore the contribution of small non-coding RNA mediated regulation on DNA demethylation dynamics and the differential expressions of key mesendoderm regulators during ESCs lineage specification. MiR-29b could potentially be applied to enrich production of mesoderm and endoderm derivatives and be further differentiated into desired organ-specific cells. PMID- 26130714 TI - A network of SMG-8, SMG-9 and SMG-1 C-terminal insertion domain regulates UPF1 substrate recruitment and phosphorylation. AB - Mammalian nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that degrades mRNAs containing premature translation termination codons. Phosphorylation of the essential NMD effector UPF1 by the phosphoinositide-3-kinase-like kinase (PIKK) SMG-1 is a key step in NMD and occurs when SMG-1, its two regulatory factors SMG-8 and SMG-9, and UPF1 form a complex at a terminating ribosome. Electron cryo-microscopy of the SMG-1-8-9-UPF1 complex shows the head and arm architecture characteristic of PIKKs and reveals different states of UPF1 docking. UPF1 is recruited to the SMG-1 kinase domain and C-terminal insertion domain, inducing an opening of the head domain that provides access to the active site. SMG-8 and SMG-9 interact with the SMG-1 C insertion and promote high-affinity UPF1 binding to SMG-1-8-9, as well as decelerated SMG-1 kinase activity and enhanced stringency of phosphorylation site selection. The presence of UPF2 destabilizes the SMG-1-8-9-UPF1 complex leading to substrate release. Our results suggest an intricate molecular network of SMG 8, SMG-9 and the SMG-1 C-insertion domain that governs UPF1 substrate recruitment and phosphorylation by SMG-1 kinase, an event that is central to trigger mRNA decay. PMID- 26130715 TI - The XRCC1 phosphate-binding pocket binds poly (ADP-ribose) and is required for XRCC1 function. AB - Poly (ADP-ribose) is synthesized at DNA single-strand breaks and can promote the recruitment of the scaffold protein, XRCC1. However, the mechanism and importance of this process has been challenged. To address this issue, we have characterized the mechanism of poly (ADP-ribose) binding by XRCC1 and examined its importance for XRCC1 function. We show that the phosphate-binding pocket in the central BRCT1 domain of XRCC1 is required for selective binding to poly (ADP-ribose) at low levels of ADP-ribosylation, and promotes interaction with cellular PARP1. We also show that the phosphate-binding pocket is required for EGFP-XRCC1 accumulation at DNA damage induced by UVA laser, H2O2, and at sites of sub nuclear PCNA foci, suggesting that poly (ADP-ribose) promotes XRCC1 recruitment both at single-strand breaks globally across the genome and at sites of DNA replication stress. Finally, we show that the phosphate-binding pocket is required following DNA damage for XRCC1-dependent acceleration of DNA single strand break repair, DNA base excision repair, and cell survival. These data support the hypothesis that poly (ADP-ribose) synthesis promotes XRCC1 recruitment at DNA damage sites and is important for XRCC1 function. PMID- 26130716 TI - Characterization of ERM transactivation domain binding to the ACID/PTOV domain of the Mediator subunit MED25. AB - The N-terminal acidic transactivation domain (TAD) of ERM/ETV5 (ERM38-68), a PEA3 group member of Ets-related transcription factors, directly interacts with the ACID/PTOV domain of the Mediator complex subunit MED25. Molecular details of this interaction were investigated using nuclear magnetic resonance (NMR) spectroscopy. The TAD is disordered in solution but has a propensity to adopt local transient secondary structure. We show that it folds upon binding to MED25 and that the resulting ERM-MED25 complex displays characteristics of a fuzzy complex. Mutational analysis further reveals that two aromatic residues in the ERM TAD (F47 and W57) are involved in the binding to MED25 and participate in the ability of ERM TAD to activate transcription. Mutation of a key residue Q451 in the VP16 H1 binding pocket of MED25 affects the binding of ERM. Furthermore, competition experiments show that ERM and VP16 H1 share a common binding interface on MED25. NMR data confirms the occupancy of this binding pocket by ERM TAD. Based on these experimental data, a structural model of a functional interaction is proposed. This study provides mechanistic insights into the Mediator-transactivator interactions. PMID- 26130717 TI - In vitro evolution of distinct self-cleaving ribozymes in diverse environments. AB - In vitro evolution experiments have long been used to evaluate the roles of RNA in both modern and ancient biology, and as a tool for biotechnology applications. The conditions under which these experiments have been conducted, however, do not reflect the range of cellular environments in modern biology or our understanding of chemical environments on the early earth, when the atmosphere and oceans were largely anoxic and soluble Fe(2+) was abundant. To test the impact of environmental factors relevant to RNA's potential role in the earliest forms of life, we evolved populations of self-cleaving ribozymes in an anoxic atmosphere with varying pH in the presence of either Fe(2+) or Mg(2+). Populations evolved under these different conditions are dominated by different sequences and secondary structures, demonstrating global differences in the underlying fitness landscapes. Comparisons between evolutionary outcomes and catalytic activities also indicate that Mg(2+) can readily take the place of Fe(2+) in supporting the catalysis of RNA cleavage at neutral pH, but not at lower pH. These results highlight the importance of considering the specific environments in which functional biopolymers evolve when evaluating their potential roles in the origin of life, extant biology, or biotechnology. PMID- 26130718 TI - Site-specific labeling of RNA by combining genetic alphabet expansion transcription and copper-free click chemistry. AB - Site-specific labeling of long-chain RNAs with desired molecular probes is an imperative technique to facilitate studies of functional RNA molecules. By genetic alphabet expansion using an artificial third base pair, called an unnatural base pair, we present a post-transcriptional modification method for RNA transcripts containing an incorporated azide-linked unnatural base at specific positions, using a copper-free click reaction. The unnatural base pair between 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds) and pyrrole-2-carbaldehyde (Pa) functions in transcription. Thus, we chemically synthesized a triphosphate substrate of 4-(4-azidopentyl)-pyrrole-2-carbaldehyde (N3-PaTP), which can be site-specifically introduced into RNA, opposite Ds in templates by T7 transcription. The N3-Pa incorporated in the transcripts was modified with dibenzocyclooctyne (DIBO) derivatives. We demonstrated the transcription of 17-, 76- and 260-mer RNA molecules and their site-specific labeling with Alexa 488, Alexa 594 and biotin. This method will be useful for preparing RNA molecules labeled with any functional groups of interest, toward in vivo experiments. PMID- 26130719 TI - DDB2 modulates TGF-beta signal transduction in human ovarian cancer cells by downregulating NEDD4L. AB - The expression of DNA damage-binding protein 2 (DDB2) has been linked to the prognosis of ovarian cancer and its underlying transcription regulatory function was proposed to contribute to the favorable treatment outcome. By applying gene microarray analysis, we discovered neural precursor cell expressed, developmentally downregulated 4-Like (NEDD4L) as a previously unidentified downstream gene regulated by DDB2. Mechanistic investigation demonstrated that DDB2 can bind to the promoter region of NEDD4L and recruit enhancer of zeste homolog 2 histone methyltransferase to repress NEDD4L transcription by enhancing histone H3 lysine 27 trimethylation (H3K27me3) at the NEDD4L promoter. Given that NEDD4L plays an important role in constraining transforming growth factor beta signaling by targeting activated Smad2/Smad3 for degradation, we investigated the role of DDB2 in the regulation of TGF-beta signaling in ovarian cancer cells. Our data indicate that DDB2 enhances TGF-beta signal transduction and increases the responsiveness of ovarian cancer cells to TGF-beta-induced growth inhibition. The study has uncovered an unappreciated regulatory mode that hinges on the interaction between DDB2 and NEDD4L in human ovarian cancer cells. The novel mechanism proposes the DDB2-mediated fine-tuning of TGF-beta signaling and its downstream effects that impinge upon tumor growth in ovarian cancers. PMID- 26130720 TI - Sense and antisense transcription are associated with distinct chromatin architectures across genes. AB - Genes from yeast to mammals are frequently subject to non-coding transcription of their antisense strand; however the genome-wide role for antisense transcription remains elusive. As transcription influences chromatin structure, we took a genome-wide approach to assess which chromatin features are associated with nascent antisense transcription, and contrast these with features associated with nascent sense transcription. We describe a distinct chromatin architecture at the promoter and gene body specifically associated with antisense transcription, marked by reduced H2B ubiquitination, H3K36 and H3K79 trimethylation and increased levels of H3 acetylation, chromatin remodelling enzymes, histone chaperones and histone turnover. The difference in sense transcription between genes with high or low levels of antisense transcription is slight; thus the antisense transcription-associated chromatin state is not simply analogous to a repressed state. Using mutants in which the level of antisense transcription is reduced at GAL1, or altered genome-wide, we show that non-coding transcription is associated with high H3 acetylation and H3 levels across the gene, while reducing H3K36me3. Set1 is required for these antisense transcription-associated chromatin changes in the gene body. We propose that nascent antisense and sense transcription have fundamentally distinct relationships with chromatin, and that both should be considered canonical features of eukaryotic genes. PMID- 26130721 TI - CTNNBL1 facilitates the association of CWC15 with CDC5L and is required to maintain the abundance of the Prp19 spliceosomal complex. AB - In order to catalyse the splicing of messenger RNA, multiple proteins and RNA components associate and dissociate in a dynamic highly choreographed process. The Prp19 complex is a conserved essential part of the splicing machinery thought to facilitate the conformational changes the spliceosome undergoes during catalysis. Dynamic protein interactions often involve highly disordered regions that are difficult to study by structural methods. Using amine crosslinking and hydrogen-deuterium exchange coupled to mass spectrometry, we describe the architecture of the Prp19 sub-complex that contains CTNNBL1. Deficiency in CTNNBL1 leads to delayed initiation of cell division and embryonic lethality. Here we show that in vitro CTNNBL1 enhances the association of CWC15 and CDC5L, both core Prp19 complex proteins and identify an overlap in the region of CDC5L that binds either CTNNBL1 or CWC15 suggesting the two proteins might exchange places in the complex. Furthermore, in vivo, CTNNBL1 is required to maintain normal levels of the Prp19 complex and to facilitate the interaction of CWC15 with CDC5L. Our results identify a chaperone function for CTNNBL1 within the essential Prp19 complex, a function required to maintain the integrity of the complex and to support efficient splicing. PMID- 26130722 TI - Enriching CRISPR-Cas9 targeted cells by co-targeting the HPRT gene. AB - The CRISPR-Cas9 system uses guide RNAs to direct the Cas9 endonuclease to cleave target sequences. It can, in theory, target essentially any sequence in a genome, but the efficiency of the predicted guide RNAs varies dramatically. If no targeted cells are obtained, it is also difficult to know why the experiment fails. We have developed a transient transfection based method to enrich successfully targeted cells by co-targeting the hypoxanthine phosphoribosyltransferase (HPRT) gene. Cells are transfected with two guide RNAs that target respectively HPRT and the gene of interest. HPRT targeted cells are selected by resistance to 6-thioguanine (6-TG) and then examined for potential alterations to the gene targeted by the co-transfected guide RNA. Alterations of many genes, such as AAVS1, Exo1 and Trex1, are highly enriched in the 6-TG resistant cells. This method works in both HCT116 cells and U2OS cells and can easily be scaled up to process multiple guide RNAs. When co-targeting fails, it is straightforward to determine whether the target gene is essential or the guide RNA is ineffective. HPRT co-targeting thus provides a simple, efficient and scalable way to enrich gene targeting events and to identify the cause of failure. PMID- 26130723 TI - Identifying novel sequence variants of RNA 3D motifs. AB - Predicting RNA 3D structure from sequence is a major challenge in biophysics. An important sub-goal is accurately identifying recurrent 3D motifs from RNA internal and hairpin loop sequences extracted from secondary structure (2D) diagrams. We have developed and validated new probabilistic models for 3D motif sequences based on hybrid Stochastic Context-Free Grammars and Markov Random Fields (SCFG/MRF). The SCFG/MRF models are constructed using atomic-resolution RNA 3D structures. To parameterize each model, we use all instances of each motif found in the RNA 3D Motif Atlas and annotations of pairwise nucleotide interactions generated by the FR3D software. Isostericity relations between non Watson-Crick basepairs are used in scoring sequence variants. SCFG techniques model nested pairs and insertions, while MRF ideas handle crossing interactions and base triples. We use test sets of randomly-generated sequences to set acceptance and rejection thresholds for each motif group and thus control the false positive rate. Validation was carried out by comparing results for four motif groups to RMDetect. The software developed for sequence scoring (JAR3D) is structured to automatically incorporate new motifs as they accumulate in the RNA 3D Motif Atlas when new structures are solved and is available free for download. PMID- 26130724 TI - Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining. AB - Mammalian DNA ligase III (LigIII) functions in both nuclear and mitochondrial DNA metabolism. In the nucleus, LigIII has functional redundancy with DNA ligase I whereas LigIII is the only mitochondrial DNA ligase and is essential for the survival of cells dependent upon oxidative respiration. The unique LigIII zinc finger (ZnF) domain is not required for catalytic activity but senses DNA strand breaks and stimulates intermolecular ligation of two DNAs by an unknown mechanism. Consistent with this activity, LigIII acts in an alternative pathway of DNA double strand break repair that buttresses canonical non-homologous end joining (NHEJ) and is manifest in NHEJ-defective cancer cells, but how LigIII acts in joining intermolecular DNA ends versus nick ligation is unclear. To investigate how LigIII efficiently joins two DNAs, we developed a real-time, fluorescence-based assay of DNA bridging suitable for high-throughput screening. On a nicked duplex DNA substrate, the results reveal binding competition between the ZnF and the oligonucleotide/oligosaccharide-binding domain, one of three domains constituting the LigIII catalytic core. In contrast, these domains collaborate and are essential for formation of a DNA-bridging intermediate by adenylated LigIII that positions a pair of blunt-ended duplex DNAs for efficient and specific intermolecular ligation. PMID- 26130725 TI - Impact of Tailored Interventions to Reduce Drug Use and Sexual Risk Behaviors Among Homeless Gay and Bisexual Men. AB - A randomized controlled trial was conducted with homeless gay and bisexual men to assess the impact of two culturally sensitive intervention programs on reduction of drug use and risky sexual behavior. In this study, gay and bisexual men between 18 and 46 years of age were randomly assigned to one of two culturally sensitive behavioral intervention programs: a Nurse Case Management Plus Contingency Management (NCM + CM; n = 204) or a Standard Education Plus Contingency Management (SE + CM; n = 210) program. Regardless of group assignment, significant and clinically relevant reductions were observed in stimulant use over time. Multivariable predictors of stimulant use at 4- and 8 month follow-up evaluations were recent injection drug use, tested positive for HIV, or for use of amphetamine. Data revealed a significant linear decline over time for those who had sex with multiple partners. Furthermore, being HIV positive was associated with reporting multiple partners, while higher homophobia scores and having children were inversely related to reports of having sex with multiple partners at follow-up. Culturally sensitive approaches are needed to successfully reduce drug use and risky sexual activities among gay and bisexual populations. PMID- 26130726 TI - Perceptions Related to Cardiovascular Disease Risk in Caucasian College Males. AB - Among younger adults, risk for cardiovascular disease (CVD) is higher among men than women. Young adult males in college engage in multiple behaviors that are associated with CVD risk. Although researchers have previously explored perceptions of factors related to hypertension in African American college males, surprisingly little is known about perceptions of CVD risk in Caucasian college males. A better understanding of these perceptions may be helpful in creating interventions to improve cardiovascular health in college men. Therefore, the purpose of this study was to explore Caucasian male college students' perceptions of CVD risk. A qualitative descriptive study using semistructured, individual interviews was conducted using a sample of 10 undergraduate Caucasian males in college (mean age 20 years) free of CVD and not enrolled in a health-related major. Interviews were audio recorded, transcribed verbatim, and analyzed for themes using content analysis. The data reflected two primary themes regarding perceptions related to cardiovascular risk: barriers to implementing healthy lifestyle choices and impact of behaviors on CVD risk. Barriers to implementing healthy lifestyles included availability of unhealthy foods, time constraints, convenience, social influences, and ignoring long-term consequences of behaviors. Students primarily emphasized the importance of diet and physical activity in reducing CVD risk. Future research should focus on interventions to overcome college-specific barriers to engaging in healthy behaviors among men. PMID- 26130727 TI - Breaking the Silence: Disordered Eating and Big Five Traits in College Men. AB - Men remain largely underrepresented in the eating disorder literature and few studies have investigated risk factors for disordered eating among men. The current study examined associations between Big Five personality traits and eating disorder symptoms in a sample of college men (N = 144). Participants completed the Eating Disorder Diagnostic Scale and Ten Item Personality Inventory online. Results suggested that openness was positively associated with purging type behaviors and that emotional stability was positively related to symptoms of anorexia nervosa and global eating pathology. Findings highlight the prevalence of eating disorder symptoms among college men and suggest that these symptoms are associated with a different constellation of personality traits than is typically reported among women. Implications for targeted prevention and intervention programs and future research are discussed. PMID- 26130728 TI - Male Urinary Incontinence: Associated Risk Factors and Electromyography Biofeedback Results in Quality of Life. AB - The aim of the current study was to determine the demographic characteristics and risk factors associated with male urinary incontinence (UI) and to assess the effectiveness and the effect on the quality-of-life of a pelvic floor muscle training (PFMT) protocol with electromyography-biofeedback (EMG-BFB) with surface electrodes. A prospective, quasi-experimental before-and-after study with a sample of 61 men out of 372 patients referred to the Pelvic Floor Unit from October 2005 to June 2012 was performed. The protocol consisted of 20 sessions of EMG-BFB supervised by a physiotherapist twice a week. The session durations were 30 minutes (118 work/rest cycles of pelvic muscles). Work lasted 3 seconds and rest 7 seconds. Patients were given standards of conduct and questionnaires (International Consultation on Incontinence-Short Form and Incontinence Quality of-Life Measure) at the beginning and at the end of the treatment. The average age was 64.85 +/- 14.34 years; 44.3% (n = 27) had benign prostatic hypertrophy, 41.9% (n = 25) had prostate malignant neoplasm, 86.9% (n = 53) had undergone prostatectomy, 16.4% (n = 10) had undergone abdominal surgery. Abdominal surgery and radical prostatectomy were significantly associated with UI (p < .05). Stress urinary incontinence was the most common type of UI (86.67%), followed by mixed urinary incontinence (8.33%) and urge urinary incontinence (5%). A significant improvement (p < .05) in both International Consultation on Incontinence-Short Form and Incontinence Quality-of-Life Measure questionnaires was observed when making comparisons regarding the results before and after the EMG-BFB treatment protocol. These results support that male UI is significantly associated with urological and abdominal surgery (including radical prostatectomy) and that EMG BFB for PFMT improves incontinence and quality of life (social embarrassment, limiting behavior, and psychosocial impact) in the three types of UI on an overall basis. PMID- 26130729 TI - Clinical Effectiveness of Weight Loss and Weight Maintenance Interventions for Men: A Systematic Review of Men-Only Randomized Controlled Trials (The ROMEO Project). AB - Men are underrepresented in obesity services, suggesting current weight loss service provision is suboptimal. This systematic review evaluated evidence-based strategies for treating obesity in men. Eight bibliographic databases and four clinical trials' registers were searched to identify randomized controlled trials (RCTs) of weight loss interventions in men only, with mean/median body mass index of >=30 kg/m2 (or >=28 kg/m2 with cardiac risk factors), with a minimum mean/median duration of >=52 weeks. Interventions included diet, physical activity, behavior change techniques, orlistat, or combinations of these; compared against each other, placebo, or a no intervention control group; in any setting. Twenty-one reports from 14 RCTs were identified. Reducing diets produced more favorable weight loss than physical activity alone (mean weight change after 1 year from a reducing diet compared with an exercise program -3.2 kg, 95% confidence interval -4.8 to -1.6 kg, reported p < .01). The most effective interventions combined reducing diets, exercise, and behavior change techniques (mean difference in weight at 1 year compared with no intervention was -4.9 kg, 95% confidence interval -5.9 to -4.0, reported p < .0001). Group interventions produced favorable weight loss results. The average reported participant retention rate was 78.2%, ranging from 44% to 100% retention, indicating that, once engaged, men remained committed to a weight loss intervention. Weight loss for men is best achieved and maintained with the combination of a reducing diet, increased physical activity, and behavior change techniques. Strategies to increase engagement of men with weight loss services to improve the reach of interventions are needed. PMID- 26130730 TI - Penile Dimensions of Diabetic and Nondiabetic Men With Erectile Dysfunction: A Case-Control Study. AB - This study aimed to report penile dimensions in diabetic and nondiabetic men with erectile dysfunction (ED) and correlate their dimensions with other study variables. A case-control study was designed through retrospective data analysis of diabetic and nondiabetic patients consulting for ED and a control group ( n = 105, each group). Study data retrieved included history, clinical evaluation, and penile dimensions (pendulous length [PL], total length [TL], and circumference [CF]) at flaccid and erect states. Results identified that patients had lower values (mean, cm) for almost all penile dimensions. The diabetic patients identified significant differences in most dimensions, whether in flaccid (PL: 7.46 vs. 7.51 and 7.81, p = .11; TL: 11.8 vs. 12.77 and 12.88, p = .000; CF: 8.84 vs. 9.1 and 9.14, p = .016) or erect state (PL: 9.66 vs. 9.61 and 10, p = .092; TL: 13.96 vs. 14.88 and 15.04, p = .000; CF: 11.56 vs. 12.06 and 11.92, p = .018) as compared with the nondiabetic patients and controls, respectively. No significant correlation was detected between the dimensions and age, durations of diabetes and ED, or erectile function scores. In conclusion, diabetic and nondiabetic patients with ED presented, in varying degrees, significant decline in their penile dimensions, and this was more prevalent in diabetic patients. As changes in penile size could be a silent corollary of comorbidities, monitoring the changes in penile dimensions should be an important component of the clinical checkup of any patient with ED, especially a diabetic patient. PMID- 26130731 TI - Engaging Men in Chronic Disease Prevention and Management Programs: A Scoping Review. AB - Chronic disease has become one of the largest health burdens facing the developed world. Men are at a higher risk of being diagnosed with chronic disease than women. Although lifestyle interventions have been shown to reduce the risk of chronic disease in participants, men are often underrepresented in such programs. The purpose of this study was to explore the individual-level and program specific factors that affect male participation rates in chronic disease prevention and management (CDPM) programs. A scoping review methodology was selected, and 25 studies met the criteria for inclusion in the review. Results showed that traditional group-based programs that focused on topics such as nutrition and physical activity were often seen by men as inherently feminine, which served as a barrier for participation. Program-specific factors that attracted men to participate in interventions included a group component with like-minded men, the use of humor in the delivery of health information, the inclusion of both nutrition and physical activity components, and the presence of some manner of competition. A past negative health event, personal concern for health status, and motivation to improve physical appearance were cited by men as facilitators to CDPM program participation. Gaps in the research are identified, and results of this study can be used to inform the development of CDPM programs that will improve the engagement and participation of men. PMID- 26130732 TI - Cause, nature and care-seeking behaviour for injuries among community-dwelling older adults, USA, 2004-2013. AB - OBJECTIVE: To describe the cause and nature of injuries, and care-seeking behaviour following injury, among community-dwelling older adults. METHODS: We used 10 years of the nationally representative Integrated Health Interview Series data, providing information on individual characteristics, cause and nature of injuries, and care-seeking behaviour for 3074 adults 65 years of age and older. Univariate and bivariate analyses were used to evaluate overall patterns and test for group-level differences. RESULTS: Approximately 40% of injuries were characterised as hip fracture, head injury and/or other fracture, with the remaining 60% consisting of other, milder types of injuries like bruises, strains and sprains. Fifty-eight per cent of injuries required a visit to the emergency room or transportation via an emergency vehicle, and 19% required hospitalisation. Injuries sustained in a fall were more likely to be serious than those due to other reasons. Older women, those ages 80+, those living with others with no spouse or partner present and those with activities of daily living/instrumental activities of daily living disabilities were more vulnerable to serious injuries and serious injury consequences relative to other older adults. CONCLUSIONS: Our results suggest that injuries, especially falls, are a pressing public health concern for the growing population of older adults. Injury prevention outreach should take extra measures to reach certain subgroups of older adults that have been identified as especially vulnerable. Because so many injuries are due to reasons other than falling and/or do not result in hospitalisation, more interventions should be designed for general injury prevention and outpatient settings. PMID- 26130733 TI - Adolescents with disability report higher rates of injury but lower rates of receiving care: findings from a national school-based survey in New Zealand. AB - OBJECTIVE: This study investigates the associations between living with a disabling condition and experiencing clinically attended injuries, risk behaviours and difficulties accessing healthcare for injury among adolescents attending secondary (high) schools in New Zealand. METHODS: A nationally representative cross-sectional self-report survey conducted in 2012 captured health and well-being data from 8500 secondary school students using a multimedia computer-assisted interview. Respondents reporting a disability or a long-term condition with functional limitations were defined as adolescents with a disabling condition (index group of interest). The association between experience of disability (or not) and injuries, related risk factors and access to healthcare was investigated using logistic regression models. RESULTS: One in six students (n=1268, 14.9%) reported a disabling condition. Compared with their peers, these students had significantly increased odds of needing treatment in the previous 12 months for an injury related to an RTC (OR 1.53; 95% CI 1.11 to 2.10), fall (OR 1.30; 95% CI 1.08 to 1.57), near drowning (OR 2.50; 95% CI 1.40 to 4.48), assault (OR 2.13; 95% CI 1.50 to 3.02) and self-harm (OR 4.25; 95% CI 3.03 to 5.96). Students with disabilities were also at increased odds of reporting they had problems accessing healthcare for injury (OR 1.51; 95% CI 1.27 to 1.81). Adolescents with disability were more likely than their peers to have been a passenger in a vehicle where the driver was under the influence of drugs (OR 1.29; 95% CI 1.03 to 1.62) or was driving dangerously (OR 1.40; 95% CI 1.21 to 1.62). CONCLUSIONS: Acknowledging the likely underestimation of effects in a mainstream school survey, adolescents with disability face elevated odds of injury and yet have poorer access to healthcare. Environmental and systemic causes of these disparities require greater attention with implementation of effective interventions. PMID- 26130734 TI - Occurrence, management and outcomes of hip fractures in patients with Parkinson's disease. AB - INTRODUCTION: Hip fractures can be debilitating, especially in patients with pre existing Parkinson's disease; they have reportedly worse outcomes than non Parkinson's disease patients. SOURCES OF DATA: A computerized literature search on PubMed, Medline, Embase, and CINAHL, supplemented by a manual search of related publications. AREAS OF AGREEMENT: Parkinson's disease patients were found to have significantly lower bone mineral density; higher incidence of falls and hip fractures; delays to receiving their Parkinson's disease medication and surgery; higher risk of pneumonia, urinary infection, pressure sores, post operative mortality; surgical complications and sequelae, including failed fixation, dislocation, longer hospital stay, re-operation; and increased risk of contralateral hip fracture. AREAS OF CONTROVERSY: Regain of mobility and return to previous residential status have been variably reported. GROWING POINTS: All Parkinson's disease patients should be screened and considered for primary prevention treatment. On admission with hip fractures, attention should be paid to avoid delays to medication, ensuring safe anaesthetic and timely surgery, and post-operative chest physiotherapy and mobilization. RESEARCH: Research is needed in minimizing the bone-resorptive effects of anti-Parkinson's disease medication. PMID- 26130735 TI - Validation of a Kinect-based telerehabilitation system with total hip replacement patients. AB - The evolving telecommunications industry combined with medical information technology has been proposed as a solution to reduce health care cost and provide remote medical services. This paper aims to validate and show the feasibility and user acceptance of using a telerehabilitation system called Kinect Rehabilitation System (KiReS) in a real scenario, with patients attending repeated rehabilitation sessions after they had a Total Hip Replacement (THR). We present the main features of KiReS, how it was set up in the considered scenario and the experimental results obtained in relation to two different perspectives: patients' subjective perceptions (gathered through questionnaires) and the accuracy of the performed exercises (by analysing the data captured using KiReS). We made a full deployment of KiReS, defining step by step all the elements of a therapy: postures, movements, exercises and the therapy itself. Seven patients participated in this trial in a total of 19 sessions, and the system recorded 3865 exercise executions. The group showed general support for telerehabilitation and the possibilities that systems such as KiReS bring to physiotherapy treatment. PMID- 26130737 TI - Doctors should refuse to check patients' immigration status, says BMA. PMID- 26130736 TI - Renal impairment in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome: incidence, treatment and outcome. AB - BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a multisystem disorder arising from underlying plasma cell dyscrasia. Renal impairment and related pathological changes have been reported, but data on its prevalence, response to therapy and impact on survival are still lacking. METHODS: We retrospectively reviewed 299 patients diagnosed with POEMS syndrome in a tertiary-care university hospital from 2000 until 2014. The estimated glomerular filtration rate (eGFR) was used to define renal impairment and response, according to International Myeloma Working Group criteria. We examined the impact of renal impairment and response on patient survival. RESULTS: Sixty-seven patients (22.4%) had renal impairment (eGFR < 60 mL/min/1.73 m(2)) at baseline. In a multivariate analysis, ascites was independently associated with renal impairment [odds ratio (OR) 12.366, P < 0.001]. Renal impairment was reversible in 66.0% of patients receiving therapy and was associated with a shorter time interval between symptom onset and treatment (OR 0.059, P = 0.043) and a vascular endothelial growth factor remission (OR 15.958, P = 0.050) in a multivariate analysis. In terms of therapy, patients with a renal response more commonly received a novel agent-based regimen (P = 0.037), which also led to a shorter response time (P = 0.001). With a median follow-up of 27.4 months, inferior survival was observed in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m(2)), but not in those with moderate dysfunction (eGFR 30-59 mL/min/1.73 m(2)), compared with patients without renal impairment. A renal response, if achieved, predicted improved survival. CONCLUSIONS: Renal impairment is a common complication of POEMS syndrome, but can be reversed with effective therapy in most cases. PMID- 26130738 TI - Takotsubo cardiomyopathy and thrombotic thrombocytopenic purpura preceding a lupus diagnosis: a case report. AB - Takotsubo cardiomyopathy, a rare stress-related cardiomyopathy, has been observed in a few cases secondary to systemic lupus erythematosus (SLE). Herein, we report an unusual case where a postmenopausal woman presented initially with Takotsubo syndrome, later developed thrombotic thrombocytopenic purpura and cerebrovascular events, initially without clinical or laboratory features of SLE. During the course of her illness, she was found to satisfy four of the Systemic Lupus International Collaborating Clinics classification criteria for a SLE diagnosis. This unique presentation of our patient, initially with Takotsubo cardiomyopathy, the development of thrombotic thrombocytopenic purpura and cerebrovascular events preceding the diagnosis of SLE illustrates the importance of clinical observation and follow-up. PMID- 26130739 TI - Institutional deliveries weakly associated with improved neonatal survival in developing countries: evidence from 192 Demographic and Health Surveys. AB - BACKGROUND: Child and maternal mortality remain high in many developing countries. A principal strategy used in low- and middle-income countries is increasing the proportion of pregnancies delivered at facilities. Although this strategy is reasonable with high quality facilities, evidence for the protective effects of facility deliveries is mixed. METHODS: We pooled 1.47 million birth records collected by the Demographic and Health Surveys to estimate the association between institutional deliveries and early neonatal mortality. Subsample analysis and instrumental variable estimation were used to assess and correct the extent to which mortality differentials are biased by an increased likelihood of facility attendance for high-risk deliveries. RESULTS: No associations between institutional deliveries and early neonatal mortality were found in the pooled sample [adjusted odds ratio (aOR) 0.995, 95% confidence interval (CI) 0.966-1.025)]. When stratified by facility type, protective effects were found for private facilities (aOR 0.876, 95% CI 0.840-0.914), but not for public hospitals or health centres. Significant protective effects were found when past behaviour was used to eliminate selection bias generated by short-term responses to medical need (aOR 0.884, 95% CI 0.814-0.961). At the community and country levels, strong positive associations were found between early neonatal mortality among facility deliveries and the prevalence of institutional deliveries. CONCLUSION: Facility deliveries have the potential to reduce early neonatal mortality in developing countries. The results presented suggest that the quality, utilization and protective effects of institutional deliveries vary widely across countries; major improvements in both utilization and quality of care will be needed to achieve further improvements in maternal and child health. PMID- 26130740 TI - Effects of vitamin D supplementation in infancy on growth, bone parameters, body composition and gross motor development at age 3-6 years: follow-up of a randomized controlled trial. AB - BACKGROUND: The long-term effects of infant vitamin D supplementation and status are unclear since there have been few controlled intervention trials and these have been small and contradictory. The Delhi Infant Vitamin D Supplementation (DIVIDS) trial found that supplementation of low-birthweight term infants with one recommended dietary allowance of vitamin D from 1 week to 6 months of age resulted in increased length and weight at 6 months. In the DIVIDS-2 study we followed up the DIVIDS children, now aged 3-6 years, to determine longer-term effects. METHODS: DIVIDS children, 446 from the vitamin D arm and 466 from the placebo arm, attended the follow-up visit. Data collection included anthropometry, blood pressure, bone structure and strength by quantitative ultrasound (QUS), gross motor tests, deuterium dilution test of body composition on a subset (n = 229) and blood samples for measurement of vitamin D status. RESULTS: Body mass index Z scores (BMIZ) were lower (adjusted P = 0.003)in the vitamin D Group [-1.18 (SD 0.92)] when compared with the placebo [-1.02 (SD 0.91)] group as a result of slightly lower weight and slightly greater height. The vitamin D group also had lower thigh circumference and arm muscle area and borderline lower mid-upper arm circumference. There were no group differences in body fat percentage, bone QUS or blood pressure and few differences in motor development measures. CONCLUSIONS: Vitamin D supplementation of low-birthweight infants in infancy resulted in children being thinner at age 3-6 years but in no differences in functional outcomes. PMID- 26130741 TI - Cohort Profile Update: Australian Longitudinal Study on Women's Health. AB - In 1996 the Australian Longitudinal Study on Women's Health recruited a nationally representative sample of more than 40,000 women in three age cohorts, born in 1973-78, 1946-51 and 1921-26. At least six waves of 3-yearly surveys have been completed. Although the focus remains on factors affecting the health and well-being of women and their access to and use of health services across urban, rural and remote areas of Australia, the study has now been considerably expanded by linkage to other health data sets. For most women who have ever participated in the study, linked records are now available for: government-subsidized non hospital services (e.g. all general practitioner visits); pharmaceutical prescriptions filled; national death index, including codes for multiple causes of death; aged care assessments and services; cancer registries; and, for most states and territories, hospital admissions and perinatal data. Additionally, a large cohort of women born in 1989-95 have been recruited. The data are available to approved collaborators, with more than 780 researchers using the data so far. Full details of the study materials and data access procedures are available at [http://www.alswh.org.au/]. PMID- 26130742 TI - Patients can self monitor oral anticoagulation, study shows. PMID- 26130745 TI - Chemoprevention of Diethylnitrosamine-Initiated and Phenobarbital-Promoted Hepatocarcinogenesis in Rats by Sulfated Polysaccharides and Aqueous Extract of Ulva lactuca. AB - Hepatocellular carcinoma (HCC) is one of the common cancers and lethal diseases worldwide. Both oxidative stress and chronic inflammation contribute to the pathogenesis of HCC. Because of limited treatment options and a grave prognosis of HCC, preventive management has been emphasized. The marine macroalgae Ulva lactuca (Ulvaceae) is consumed by humans and livestock because of its nutritional value. Recent studies showed that various extracts of U. lactuca possess antiviral, antiplasmodial, antinephrotoxic, antioxidant, and anti-inflammatory properties. However, very limited information is available on anticancer potential of U. lactuca with no reports on liver cancer chemopreventive efficacy of this marine algae. Accordingly, the present study was initiated to evaluate the possible antihepatocarcinogenic effects and antioxidant mechanisms of action of various U. lactuca extracts against a clinically relevant rodent model of HCC. Initiation of hepatocarcinogenesis was performed in Sprague-Dawley rats by a single injection of dietary carcinogen diethylnitrosamine (DENA, 200 mg/kg, intraperitoneally), followed by promotion with phenobarbital (0.05%) in drinking water. The rats were fed with daily oral dose (50 mg/kg) of polysaccharide sulfate or aqueous extract of U. lactuca for 2, 12, and 24 weeks. At these timepoints, blood samples were taken to measure hepatic injury markers, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, and bilirubin. The liver tissue was harvested for measurement of hepatic oxidative indices, including lipid peroxidation, reduced glutathione, nitric oxide, catalase, superoxide dismutase, glutathione reductase, and glutathione S-transferase. Hepatic histopathology, immunohistochemical analysis of cell proliferation and apoptosis by DNA fragmentation assay were performed. Our results clearly indicate that sulfated polysaccharides of U. lactuca exert a marked chemoprevention of DENA-initiated hepatocarcinogenesis through inhibition of abnormal cell proliferation and induction of apoptosis. A modest inhibition rat liver carcinogenesis was observed with the aqueous extract. The sulfated polysaccharides altered serum parameters of hepatic damage and modulated various components of the hepatic enzymatic and nonenzymatic antioxidant defense systems. The sulfated polysaccharides from U. lactuca may have unique properties of providing protection against DENA-induced oxidative stress which could contribute to chemoprevention of experimental hepatocarcinogenesis. U. lactuca sulfated polysaccharides could be developed as chemopreventive and therapeutic drug against human HCC. PMID- 26130743 TI - From the clinician's point of view - What is the status quo of positron emission tomography in patients with brain tumors? AB - The most common type of primary brain tumor is malignant glioma. Despite intensive therapeutic efforts, the majority of these neoplasms remain incurable. Imaging techniques are important for initial tumor detection and comprise indispensable tools for monitoring treatment. Structural imaging using contrast enhanced MRI is the method of choice for brain tumor surveillance, but its capacity to differentiate tumor from nonspecific tissue changes can be limited, particularly with posttreatment gliomas. Metabolic imaging using positron emission-tomography (PET) can provide relevant additional information, which may allow for better assessment of tumor burden in ambiguous cases. Specific PET tracers have addressed numerous molecular targets in the last decades, but only a few have achieved relevance in routine clinical practice. At present, PET studies using radiolabeled amino acids appear to improve clinical decision-making as these tracers can offer better delineation of tumor extent as well as improved targeting of biopsies, surgical interventions, and radiation therapy. Amino acid PET imaging also appears useful for distinguishing glioma recurrence or progression from postradiation treatment effects, particularly radiation necrosis and pseudoprogression, and provides information on histological grading and patient prognosis. In the last decade, the tracers O-(2-[(18)F]fluoroethyl)-L tyrosine (FET) and 3,4-dihydroxy-6-[(18)F]-fluoro-L-phenylalanine (FDOPA) have been increasingly used for these indications. This review article focuses on these tracers and summarizes their recent applications for patients with brain tumors. Current uses of tracers other than FET and FDOPA are also discussed, and the most frequent practical questions regarding PET brain tumor imaging are reviewed. PMID- 26130746 TI - Electronic medication reconciliation and medication errors. AB - OBJECTIVE: To measure the impact of electronic medication reconciliation implementation on reports of admission medication reconciliation errors (MREs). DESIGN: Quality improvement project with time-series design. SETTING: A large, urban, tertiary care children's hospital. PARTICIPANTS: All admitted patients from 2011 and 2012. INTERVENTIONS: Implementation of an electronic medication reconciliation tool for hospital admissions and regular compliance reporting to inpatient units. The tool encourages active reconciliation by displaying the pre admission medication list and admission medication orders side-by-side. MAIN OUTCOME MEASURE: Rate of non-intercepted admission MREs identified via a voluntary reporting system. RESULTS: During the study period, there were 33 070 hospital admissions. The pre-admission medication list was consistently recorded electronically throughout the study period. In the post-intervention period, the use of the electronic medication reconciliation tool increased to 84%. Reports identified 146 admission MREs during the study period, including 95 non intercepted errors. Pre- to post-intervention, the rate of non-intercepted errors decreased by 53% (P = 0.02). Reported errors were categorized as intercepted potential adverse drug events (ADEs) (35%), non-intercepted potential ADEs (42%), minor ADEs (22%) or moderate ADEs (1%). There were no reported MREs that resulted in major or catastrophic ADEs. CONCLUSIONS: We successfully implemented an electronic process for admission medication reconciliation, which was associated with a reduction in reports of non-intercepted admission MREs. PMID- 26130744 TI - Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma. AB - BACKGROUND: The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy. METHODS: This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0 2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS). RESULTS: One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately. CONCLUSIONS: Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies. CLINICAL TRIALS REGISTRATION NR: ACTRN12610000915055. PMID- 26130747 TI - Cordycepin protected against the TNF-alpha-induced inhibition of osteogenic differentiation of human adipose-derived mesenchymal stem cells. AB - Cordycepin, 3'-deoxyadenosine, is an effective component isolated from the rare Chinese caterpillar fungus Cordyceps militaris. It exerts potent anti inflammatory actions in different cell and animal models. However, its action remains unclear on the TNF-alpha-induced inhibition of osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs). In the present study, we demonstrated that cordycepin induced cell death at 20 and 40 MUg/mL. Interestingly, 10 MUg/mL cordycepin abrogated the cell death induced by 20 ng/mL TNF-alpha. Meanwhile, cordycepin exhibited a dose-dependent regulation of the osteogenesis of human ADMSCs: it promoted the differentiation at 10 MUg/mL, whereas inhibited differentiation at 40 MUg/mL. Furthermore, we discovered that 10 MUg/mL cordycepin protected against the TNF-alpha (induced inhibition of osteogenic differentiation of human ADMSCs. It was also revealed that 10 MUg/mL cordycepin restored Runx2 and Osx mRNA levels, which were significantly inhibited by TNF-alphaduring osteogenesis. At the same time, we found that 10 MUg/mL cordycepin suppressed TNF-alpha-activated NF-kappaB signaling, by inhibiting IkappaBalpha phosphorylation and subsequent p65 release and translocation into the cell nucleus. Of clinical interest, the present study revealed mechanisms involved in inflammatory cytokine-inhibited osteogenesis, and it highlights the potential of cordycepin to promote the osteogenesis of human ADMSCs in cell-based therapy for inflammatory bone diseases. PMID- 26130748 TI - Severe craniocerebral trauma with sequelae caused by Flash-Ball(r) shot, a less lethal weapon: Report of one case and review of the literature. AB - The use of Flash-Ball(r) as a non-lethal weapon by several special units within the police and police forces started in France in 1995. Little literature is available concerning injuries caused by Flash-Ball(r) shooting. However, we report the case of a healthy 34-year-old male victim of a Flash-Ball(r) shooting during a riot following a sports event. This young man presented serious craniocerebral injuries with a left temporal fracture, moderate cerebral oedema, fronto-temporal haemorrhagic contusion along with an extra-dural hematoma and subarachnoid hemorrhage requiring neurological and rehabilitation care for two months leaving important sequelae. Although the risk is obviously lower than with firearms, Flash-Ball(r) is nonetheless potentially lethal and may cause serious physical injuries, particularly after a shot to the head. PMID- 26130749 TI - Decision tree analysis as a supplementary tool to enhance histomorphological differentiation when distinguishing human from non-human cranial bone in both burnt and unburnt states: A feasibility study. AB - This feasibility study was undertaken to describe and record the histological characteristics of burnt and unburnt cranial bone fragments from human and non human bones. Reference series of fully mineralized, transverse sections of cranial bone, from all variables and specimen states, were prepared by manual cutting and semi-automated grinding and polishing methods. A photomicrograph catalogue reflecting differences in burnt and unburnt bone from human and non humans was recorded and qualitative analysis was performed using an established classification system based on primary bone characteristics. The histomorphology associated with human and non-human samples was, for the main part, preserved following burning at high temperature. Clearly, fibro-lamellar complex tissue subtypes, such as plexiform or laminar primary bone, were only present in non human bones. A decision tree analysis based on histological features provided a definitive identification key for distinguishing human from non-human bone, with an accuracy of 100%. The decision tree for samples where burning was unknown was 96% accurate, and multi-step classification to taxon was possible with 100% accuracy. The results of this feasibility study strongly suggest that histology remains a viable alternative technique if fragments of cranial bone require forensic examination in both burnt and unburnt states. The decision tree analysis may provide an additional but vital tool to enhance data interpretation. Further studies are needed to assess variation in histomorphology taking into account other cranial bones, ontogeny, species and burning conditions. PMID- 26130750 TI - Homicide committed by psychiatric patients: Psychiatrists' liability in Italian law cases. AB - Interest in psychiatrists' professional liability in Italy has increased in recent years because of the number of medical malpractice claims. Professional liability for failure to prevent violent behaviour by psychiatric patients is particularly debated. This study describes three Italian cases in which health professionals - physicians and nurses - were found guilty of manslaughter for murders committed by psychiatric patients. Examination of the cases focuses on claims of malpractice, patients' characteristics, the circumstances of the homicide and the reasons for the court's judgment. In particular, the predictability of violent behaviour and the concept of causal links are examined in detail. The cases provide an opportunity for a study of comparative jurisprudence. The topics discussed are relevant not only to practicing psychiatrists but also to experts assessing medical liability in cases of criminal acts committed by psychiatric patients. PMID- 26130751 TI - The embalming of John of Lancaster, first Duke of Bedford (1435 AD): A forensic analysis. AB - During the Middle Ages and Renaissance, embalming the cadaver of the elite was common practice, being a highly technical treatment mixing vegetal and mineral substances. To assess the exact kind of embalming reserved for the dead body (with the practical necessities of desiccation and good odour), we performed a full biomedical analysis of the mummified remains of John Plantagenet of Lancaster, first Duke of Bedford, regent of France for his nephew, the English King Henri VI (died 1435 AD). Here, we show, among other aspects, that the body was embalmed using substances whose origins were in apothecary and botany: mercury, myrtle, mint, frankincense, lime and, possibly, cinnamon and copper. PMID- 26130752 TI - Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. AB - AIMS: In myocardial ischaemia, vascular endothelial growth factor (VEGF) induces permeability by activating a signalling pathway that includes VEGF receptor 2 (VEGFR2), resulting in increased oedema and inflammation and thereby expanding the area of tissue damage. In this study, we investigated the role of receptor interacting protein 2 (Rip2) in VEGF signalling and myocardial ischaemia/reperfusion injury. METHODS AND RESULTS: To determine whether Rip2 has a role in VEGF signalling, we used cultured endothelial cells in which Rip2 was or was not inactivated. In Rip2-deficient endothelial cells, stimulation with VEGF resulted in more rapid kinetics of VEGFR2 phosphorylation than in control cells. Rip2 deficiency also enhanced VEGF-induced activation of ERK1/2, suggesting an increased propensity for endothelial permeability. In a mouse model of myocardial ischaemia, Rip2 deficiency resulted in enhanced vascular permeability, increased oedema and expanding area of myocardial damage, and markedly reduced heart function after long-term follow-up. CONCLUSION: Our results show that Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. These findings indicate that Rip2 may be a promising novel therapeutic target to reduce excess vascular permeability in ischaemic heart disease. PMID- 26130753 TI - An interview with Austin Smith. PMID- 26130754 TI - LIF signaling in stem cells and development. AB - Leukemia inhibitory factor (LIF) is a member of the interleukin-6 (IL-6) cytokine family. All members of this family activate signal transducer and activator of transcription 3 (STAT3), a transcription factor that influences stem and progenitor cell identity, proliferation and cytoprotection. The role of LIF in development was first identified when LIF was demonstrated to support the propagation of mouse embryonic stem cells. Subsequent studies of mice deficient for components of the LIF pathway have revealed important roles for LIF signaling during development and homeostasis. Here and in the accompanying poster, we provide a broad overview of JAK-STAT signaling during development, with a specific focus on LIF-mediated JAK-STAT3 activation. PMID- 26130756 TI - Computational modelling of embryonic stem-cell fate control. AB - The maintenance of pluripotency in embryonic stem cells (ESCs), its loss during lineage specification or its re-induction to generate induced pluripotent stem cells are central topics in stem cell biology. To uncover the molecular basis and the design principles of pluripotency control, a multitude of experimental, but also an increasing number of computational, studies have been published. Here, we consider recent reports that apply computational or mathematical modelling approaches to describe the regulatory processes that underlie cell fate decisions in mouse ESCs. We summarise the principles, the strengths and potentials but also the limitations of different computational strategies. PMID- 26130755 TI - The never-ending story: from pluripotency to plant developmental plasticity. AB - Plants are sessile organisms, some of which can live for over a thousand years. Unlike most animals, plants employ a post-embryonic mode of development driven by the continuous activity of pluripotent stem cells. Consequently, plants are able to initiate new organs over extended periods of time, and many species can readily replace lost body structures by de novo organogenesis. Classical studies have also shown that plant tissues have a remarkable capacity to undergo de differentiation and proliferation in vitro, highlighting the fact that plant cell fate is highly plastic. This suggests that the mechanisms regulating fate transitions must be continuously active in most plant cells and that the control of cellular pluripotency lies at the core of diverse developmental programs. Here, we review how pluripotency is established in plant stem cell systems, how it is maintained during development and growth and re-initiated during regeneration, and how these mechanisms eventually contribute to the amazing developmental plasticity of plants. PMID- 26130758 TI - Adaptation is not required to explain the long-term response of axons to molecular gradients. PMID- 26130757 TI - FGF8 coordinates tissue elongation and cell epithelialization during early kidney tubulogenesis. AB - When a tubular structure forms during early embryogenesis, tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner. We here demonstrate, using the Wolffian duct (WD) of early chicken embryos, that this coordination is regulated by the expression of FGF8, which shifts posteriorly during body axis elongation. FGF8 acts as a chemoattractant on the leader cells of the elongating WD and prevents them from epithelialization, whereas static ('rear') cells that receive progressively less FGF8 undergo epithelialization to form a lumen. Thus, FGF8 acts as a binary switch that distinguishes tubular elongation from lumen formation. The posteriorly shifting FGF8 is also known to regulate somite segmentation, suggesting that multiple types of tissue morphogenesis are coordinately regulated by macroscopic changes in body growth. PMID- 26130759 TI - Plasma membrane-bound AGC3 kinases phosphorylate PIN auxin carriers at TPRXS(N/S) motifs to direct apical PIN recycling. PMID- 26130760 TI - HbA1c and Lower Extremity Amputation Risk in Patients With Diabetes: A Meta Analysis. AB - In this meta-analysis, we aimed to assess glycosylated hemoglobin (HbA1c) level and lower extremity amputation (LEA) risk in patients with diabetes. Systematic computerized searches of the PubMed and Web of Knowledge were performed. We compared HbA1c level between groups with LEA and without LEA by meta-analysis; we also examined the dose-response relationship between HbA1c level and LEA risk. Sixteen studies were included in the meta-analysis. Eleven studies with 43,566 patients compared HbA1c between groups with and without LEA. The mean HbA1c (%) ranged from 8.3 to 12.5 in the group with LEA and from 7.4 to 11.3 in the group without LEA. The pooled weighted mean difference was 1.110 (95% confidence interval = 0.510-1.709; Z = 3.63, P = .008). The funnel plot was symmetrical, and Begg's test (z = 0.00, P = 1.000) and Egger's test (t = -0.02, P = .984) suggested no significant publication bias. Six studies with 109,933 patients included in the dose-response meta-analysis. The LEA incidence ranged from 0.3% to 14.6% between different HbA1c levels. Dose-response meta-analysis showed statistically significant association between HbA1c and LEA risk (chi(2) = 65.51, P = .000). In linear model, the odds ratio for LEA incidence was 1.229 (95% confidence interval = 1.169-1.292) for every 1% HbA1c increase. In the spline model, the odds ratio of LEA risk increased with HbA1c levels, especially when HbA1c ranged from 5% to 9%. Our meta-analysis indicates that high level of HbA1c is an important risk factor for LEA in patients with diabetes. This evidence supports the strategy for lowering glucose levels to reduce amputation in patients with diabetes. PMID- 26130761 TI - Analysis of Ulcer Recurrences After Metatarsal Head Resection in Patients Who Underwent Surgery to Treat Diabetic Foot Osteomyelitis. AB - Metatarsal head resection is a common and standardized treatment used as part of the surgical routine for metatarsal head osteomyelitis. The aim of this study was to define the influence of the amount of the metatarsal resection on the development of reulceration or ulcer recurrence in patients who suffered from plantar foot ulcer and underwent metatarsal surgery. We conducted a prospective study in 35 patients who underwent metatarsal head resection surgery to treat diabetic foot osteomyelitis with no prior history of foot surgeries, and these patients were included in a prospective follow-up over the course of at least 6 months in order to record reulceration or ulcer recurrences. Anteroposterior plain X-rays were taken before and after surgery. We also measured the portion of the metatarsal head that was removed and classified the patients according the resection rate of metatarsal (RRM) in first and second quartiles. We found statistical differences between the median RRM in patients who had an ulcer recurrence and patients without recurrences (21.48 +/- 3.10% vs 28.12 +/- 10.8%; P = .016). Seventeen (56.7%) patients were classified in the first quartile of RRM, which had an association with ulcer recurrence (P = .032; odds ratio = 1.41; 95% confidence interval = 1.04-1.92). RRM of less than 25% is associated with the development of a recurrence after surgery in the midterm follow-up, and therefore, planning before surgery is undertaken should be considered to avoid postsurgical complications. PMID- 26130762 TI - Promoted Interaction of Nuclear Factor-kappaB With Demethylated Purinergic P2X3 Receptor Gene Contributes to Neuropathic Pain in Rats With Diabetes. AB - Painful diabetic neuropathy is a common complication of diabetes produced by mechanisms that as yet are incompletely defined. The aim of this study was to investigate the roles of nuclear factor-kappaB (NF-kappaB) in the regulation of purinergic receptor P2X ligand-gated ion channel 3 (P2X3R) plasticity in dorsal root ganglion (DRG) neurons of rats with painful diabetes. Here, we showed that hindpaw pain hypersensitivity in streptozocin-induced diabetic rats was attenuated by treatment with purinergic receptor antagonist suramin or A-317491. The expression and function of P2X3Rs was markedly enhanced in hindpaw-innervated DRG neurons in diabetic rats. The CpG (cytosine guanine dinucleotide) island in the p2x3r gene promoter region was significantly demethylated, and the expression of DNA methyltransferase 3b was remarkably downregulated in DRGs in diabetic rats. The binding ability of p65 (an active form of NF-kappaB) with the p2x3r gene promoter region and p65 expression were enhanced significantly in diabetes. The inhibition of p65 signaling using the NF-kappaB inhibitor pyrrolidine dithiocarbamate or recombinant lentiviral vectors designated as lentiviral vector p65 small interfering RNA remarkably suppressed P2X3R activities and attenuated diabetic pain hypersensitivity. Insulin treatment significantly attenuated pain hypersensitivity and suppressed the expression of p65 and P2X3Rs. Our findings suggest that the p2x3r gene promoter DNA demethylation and enhanced interaction with p65 contributes to P2X3R sensitization and diabetic pain hypersensitivity. PMID- 26130763 TI - Reduction in SGLT1 mRNA Expression in the Ventromedial Hypothalamus Improves the Counterregulatory Responses to Hypoglycemia in Recurrently Hypoglycemic and Diabetic Rats. AB - The objective of this study was to determine whether the sodium-glucose transporter SGLT1 in the ventromedial hypothalamus (VMH) plays a role in glucose sensing and in regulating the counterregulatory response to hypoglycemia, and if so, whether knockdown of in the VMH can improve counterregulatory responses to hypoglycemia in diabetic rats or rats exposed to recurrent bouts of hypoglycemia (RH). Normal Sprague-Dawley rats as well as RH or streptozotocin (STZ)-diabetic rats received bilateral VMH microinjections of an adenoassociated viral vector containing either the SGLT1 short hairpin RNA (shRNA) or a scrambled RNA sequence. Subsequently, these rats underwent a hypoglycemic clamp to assess hormone responses. In a subgroup of rats, glucose kinetics was determined using tritiated glucose. The shRNA reduced VMH SGLT1 expression by 53% in nondiabetic rats, and this augmented glucagon and epinephrine responses and hepatic glucose production during hypoglycemia. Similarly, SGLT1 knockdown improved the glucagon and epinephrine responses in RH rats and restored the impaired epinephrine response to hypoglycemia in STZ-diabetic animals. These findings suggest that SGLT1 in the VMH plays a significant role in the detection and activation of counterregulatory responses to hypoglycemia. Inhibition of SGLT1 may offer a potential therapeutic target to diminish the risk of hypoglycemia in diabetes. PMID- 26130764 TI - Reversal of New-Onset Type 1 Diabetes With an Agonistic TLR4/MD-2 Monoclonal Antibody. AB - Type 1 diabetes (T1D) is currently an incurable disease, characterized by a silent prodromal phase followed by an acute clinical phase, reflecting progressive autoimmune destruction of insulin-producing pancreatic beta-cells. Autoreactive T cells play a major role in beta-cell destruction, but innate immune cell cytokines and costimulatory molecules critically affect T-cell functional status. We show that an agonistic monoclonal antibody to TLR4/MD-2 (TLR4-Ab) reverses new-onset diabetes in a high percentage of NOD mice. TLR4-Ab induces antigen-presenting cell (APC) tolerance in vitro and in vivo, resulting in an altered cytokine profile, decreased costimulatory molecule expression, and decreased T-cell proliferation in APC:T-cell assays. TLR4-Ab treatment increases T-regulatory cell (Treg) numbers in both the periphery and the pancreatic islet, predominantly expanding the Helios(+)Nrp-1(+)Foxp3(+) Treg subset. TLR4-Ab treatment in the absence of B cells in NOD.scid mice prevents subsequent T cell mediated disease, further suggesting a major role for APC tolerization in disease protection. Specific stimulation of the innate immune system through TLR4/MD-2, therefore, can restore tolerance in the aberrant adaptive immune system and reverse new-onset T1D, suggesting a novel immunological approach to treatment of T1D in humans. PMID- 26130765 TI - Editorial: Passive aggressive avoidance of SAMHD1 restriction by HIV-1. PMID- 26130767 TI - Training medical providers in evidence-based approaches to suicide prevention. AB - Suicide is a significant issue in the United States and worldwide, and its prevention is a public health imperative. Primary care practices are an important setting for suicide prevention, as primary care providers have more frequent contact with patients at risk for suicide than any other type of health-care provider. The Western Interstate Commission for Higher Education, in partnership with the Suicide Prevention Resource Center, has developed a Suicide Prevention Toolkit and an associated training curriculum. These resources support the education of primary care providers in evidence-based strategies for identifying and treating patients at risk for suicide. The application of this curriculum to post-graduate medical training is presented here. PMID- 26130766 TI - A facile method for controlling the reaction equilibrium of sphingolipid ceramide N-deacylase for lyso-glycosphingolipid production. AB - Lyso-glycosphingolipids (lyso-GSLs), the N-deacylated forms of glycosphingolipids (GSLs), are important synthetic intermediates for the preparation of GSL analogs. Although lyso-GSLs can be produced by hydrolyzing natural GSLs using sphingolipid ceramide N-deacylase (SCDase), the yield for this reaction is usually low because SCDase also catalyzes the reverse reaction, ultimately establishing an equilibrium between hydrolysis and synthesis. In the present study, we developed an efficient method for controlling the reaction equilibrium by introducing divalent metal cation and detergent in the enzymatic reaction system. In the presence of both Ca(2+) and taurodeoxycholate hydrate, the generated fatty acids were precipitated by the formation of insoluble stearate salts and pushing the reaction equilibrium toward hydrolysis. The yield of GM1 hydrolysis can be achieved as high as 96%, with an improvement up to 45% compared with the nonoptimized condition. In preparative scale, 75 mg of lyso-GM1 was obtained from 100 mg of GM1 with a 90% yield, which is the highest reported yield to date. The method can also be used for the efficient hydrolysis of a variety of GSLs and sphingomyelin. Thus, this method should serve as a facile, easily scalable, and general tool for lyso-GSL production to facilitate further GSL research. PMID- 26130768 TI - Use of a specialty clinic to teach a standardized approach to mood disorders in a family medicine residency. AB - The Mood Disorder Clinic was started at the Cone Family Medicine Residency in 2004 with the threefold purpose of providing a patient care service to a largely uninsured or underinsured population; teaching Family Medicine resident physicians how to more accurately identify, diagnose, and treat mood disorders in their patients; and modeling a team-based approach to addressing mental stress, distress, and dysfunction in the primary care setting. The authors present the logistics of the clinic and the standard approach to mood issues that is taught to resident physicians. Formal feedback suggests that the resident physicians find the experience useful in developing psychiatric knowledge and skills. PMID- 26130769 TI - Designing and implementing a resiliency program for family medicine residents. AB - Family medicine residents are at risk for burnout due to extended work hours, lack of control over their work schedule, and challenging work situations and environments. Building resiliency can prevent burnout and may improve a resident's quality of life and health behavior. This report describes a program designed to build resiliency, the ability to bounce back from stress, in family medicine residents in a medium sized U.S. residency training program. Interactive sessions emphasized building self-awareness, coping skills, strengths and meaning in work, time management, self-care, and connections in and outside of medicine to support resident well-being. System changes which fostered wellness were also implemented. These changes included increasing the availability of fresh fruits in the conference and call room, purchasing an elliptical exercise machine for the on call room, and offering a few minutes of mindfulness meditation daily to the inpatient residents. Results to date show excellent acceptance of the program by trainees, increased consumption of nutritious foods, more personal exercise, and self-reported decreased overreactions to stress. Resiliency programs can effectively serve to meet accreditation requirements while fostering residents' abilities to balance personal and professional demands. PMID- 26130770 TI - Teaching family medicine residents brief interventions for alcohol misuse. AB - Across the lifespan, alcohol misuse affects a large percentage of patients seen in primary care clinics. It can lead to alcohol use disorders, ranging from risky use to alcohol dependence. Alcohol use disorders frequently complicate acute and chronic illnesses of patients seen in FM clinics. Screening patients for alcohol and substance use has become a standard of practice in most primary care settings. This report describes how a family medicine residency program solidified a residency curriculum in substance abuse screening, assessment, and brief intervention by merging three presentation-style didactics into a blended approach. The curriculum combines didactic teaching, motivational interviewing, and behavioral rehearsal of clinical practice skills. Qualitative feedback suggests that the curriculum has been successful in exposing residents to a variety of practical assessment methods and, through rehearsal, has improved resident confidence in addressing alcohol use and misuse in a primary care population. PMID- 26130771 TI - The respiratory health benefits of quitting cannabis use. PMID- 26130772 TI - Animal fur and asthma: an indoor farmyard phenomenon? PMID- 26130773 TI - Defining airflow limitation and chronic obstructive pulmonary disease: the role of outcome studies. PMID- 26130774 TI - Cystic fibrosis in Europe: patients live longer but are we ready? PMID- 26130775 TI - Never too old: beneficial neurobehavioural effects of continuous positive airway pressure in the elderly. PMID- 26130776 TI - Insights into idiopathic pulmonary fibrosis in the real world. PMID- 26130777 TI - Targeted therapies: detrimental treatment for nonsmall cell lung cancer without driver mutations. PMID- 26130778 TI - The Transatlantic Trade and Investment Partnership: Trojan horse or positive force for health? PMID- 26130780 TI - Clinical and prognostic heterogeneity of C and D GOLD groups. PMID- 26130781 TI - Airway diseases and inflammatory bowel diseases: is it something in the air (pollution)? PMID- 26130782 TI - Bedaquiline: finding the pores on the pot. PMID- 26130783 TI - Bedaquiline: finding the pores on the pot. PMID- 26130785 TI - Role of high sensitivity C-reactive protein and other risk factors in intracranial and extracranial artery occlusion in patients with ischaemic stroke. AB - OBJECTIVE: A retrospective case-control study to identify stroke-associated risk factors and quantify serum C-reactive protein in patients with ischaemic stroke, with or without intracranial and/or extracranial artery occlusion (IEAO). METHODS: Patients with ischaemic stroke and internal carotid artery occlusion (ICAO), middle cerebral artery occlusion (MCAO), ICAO + MCAO, or no IEAO (control patients) were retrospectively recruited. Data regarding stroke-associated risk factors were retrieved from medical records. High sensitivity (hs)-CRP was quantified within 3 days of hospital admission. RESULTS: Patients with ICAO (n = 89), MCAO (n = 74) and ICAO + MCAO (n = 29) had significantly higher serum hs-CRP concentrations, and were significantly more likely to have coronary heart disease, a history of stroke, and more than three stroke-associated risk factors than control patients (n = 84). CONCLUSIONS: Coronary heart disease and a history of stroke are risk factors for ischaemic stroke with IEAO. Hs-CRP may be used as a marker for IEAO. PMID- 26130786 TI - The Spectrum of Infectious Diseases in Kidney Transplantation: A Review of the Classification, Pathogens and Clinical Manifestations. AB - Kidney transplantation is the treatment-of-choice for a significant number of patients with end-stage renal disease. Renal transplant recipients (RTRs) benefit from a longer life expectancy, with a better quality of life. Despite, recent accomplishments in the field of kidney transplantation, both short- and long term, surgical and medical complications still exist. Among these complications, cardiovascular disease, carcinogenesis and infections are the most important. Infectious diseases constitute the most common complications after renal transplantation and the second most common cause of death among RTRs with a functioning graft. Theoretically, all infectious pathogens could cause disease in immunocompromised RTRs, yet among these, one could identify more important ones, such as the Enterobacteriaceae, causing urinary tract infections; pneumonia due to Pneumocystis jirovecii; Candida species which cause invasive fungal infections; herpes viruses; hepatitis viruses and parasites. Early diagnosis and effective treatment are key elements in salvaging both the allograft and the patient. However, clinical manifestations and diagnosis of such infectious diseases are not easily identified due to the altered state of immune response of the RTR. Thus, apart from possessing a deep knowledge of the etiology and the treatment options in each case, transplant physicians should also always remain alert when dealing with RTRs. PMID- 26130787 TI - Genetic and Apoptotic Changes in Lungs of Mice Flown on the STS-135 Mission in Space. AB - AIM: The goal of the study was to evaluate changes in lung status due to spaceflight stressors that include radiation above levels found on Earth. MATERIALS AND METHODS: Within hours after return from a 13-day mission in space onboard the Space Shuttle Atlantis, C57BL/6 mice (FLT group) were euthanized; mice housed on the ground in similar animal enclosure modules served as controls (AEM group). Lung tissue was collected to evaluate the expression of genes related to extracellular matrix (ECM)/adhesion and stem cell signaling. Pathway analysis was also performed. In addition, immunohistochemistry for stem cell antigen-1 (SCA-1), the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptosis, and staining for histological characteristics were performed. RESULTS: There were 18/168 genes significantly modulated in lungs from the FLT group (p<0.05 vs. AEM); 17 of these were up regulated and one was down-regulated. The greatest effect, namely a 5.14-fold increase, was observed on Spock1 (also known as Spark/osteonectin), encoding a multi-functional protein that has anti-adhesive effects, inhibits cell proliferation and regulates activity of certain growth factors. Additional genes with increased expression were cadherin 3 (Cdh3), collagen, type V, alpha 1 (Col5a1), integrin alpha 5 (Itga5), laminin, gamma 1 (Lamc1), matrix metallopeptidase 14 (Mmp14), neural cell adhesion molecule 1 (Ncam1), transforming growth factor, beta induced (Tgfbi), thrombospondin 1 (Thbs1), Thbs2, versican (Vcan), fibroblast growth factor receptor 1 (Fgfr1), frizzled homolog 6 (Fzd6), nicastrin (Ncstn), nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 (Nfatc4), notch gene homolog 4 (Notch4) and vang-like 2 (Vangl2). The down-regulated gene was Mmp13. Staining for SCA-1 protein showed strong signal intensity in bronchiolar epithelial cells of FLT mice (p<0.05 vs. AEM). TUNEL positivity was also significantly higher in the FLT mice (p<0.05 vs. AEM), but no consistent histological differences were noted. CONCLUSION: The results demonstrate that spaceflight-related stress had a significant impact on lung integrity, indicative of tissue injury and remodeling. PMID- 26130788 TI - Hematogenic Dissemination of Triple-negative Versus Hormonal Receptor-positive Breast Cancer Cells. AB - The aim of this study was to characterize the hematogeneous spread, in vivo, of breast cancer (BC) cell lines that express hormonal receptors (HR) comparing with triple-negative (TN) BC, particularly considering the lung and liver. Female Balb/c nu nu mice (n=30) were injected with two breast cancer cell lines (MCF7 and HCC1806). Nuclear medicine imaging with Technetium ((99m)Tc)-hydroxymethylene diphosphonate ((99m)Tc-HMDP) and (99m)Tc-Hexakis 2-methoxy-2 methylpropylisonitrile (MIBI) were performed between the 7th and 8th weeks after injection. The histological metastatic foci were analyzed by morphometric and immunohistochemistry studies regarding estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (ERBB2) and cytokeratin (CK)-5/6. The mean area of lung metastasis in MCF7 cases was significantly higher (p=0.023), although the number of liver foci was higher in the HCC1806 group (p=0.006). Logistic regression revealed a potentiating model for liver metastasis with HCC1806 cells (odds ratio=16; p=0.03). The number and area of lung metastatic foci were not predictive of liver dissemination. Lung metastasis study showed ER positivity in 57.1% of the MCF7 group, compared to 80% of the HCC1806 group. PR was positive in 42.9% of MCF7 cases and negative in 60% of HCC1806 cases. HR-positive cells developed massive lung metastization. TN cells seem to potentiate liver metastasis. ER, PR, ERBB2 and basal-like CK expression in metastases was not uniformly correlated with that of primary tumor cells. PMID- 26130789 TI - Characteristic Comparison Between 131I-Interferon-alpha and 131I-Interferon-alpha Immunoglobulin-Fc Hybrid Protein in Rats Using Molecular Imaging. AB - BACKGROUND/AIM: Interferon-alpha (IFN-alpha) is produced to act locally and transiently with a relatively short circulation half-life in vivo. Hybridization of IFN-alpha with human immunoglobulin Fc, renamed as IFN-alpha-Fc, may overcome this limitation. In the present study, (131)I-IFN-alpha-Fc and (131)I-IFN-alpha were compared in the aspects of stability, pharmacokinetics, tissue distribution and molecular imaging quality in an animal model. MATERIALS AND METHODS: Both IFN alpha-Fc and IFN-alpha were labelled with (131)I. Biodistributions and pharmacokinetics of both labelled proteins in Sprague-Dawley rats were assayed. Micro-single-photon emission computed tomography/computed tomography was used to non-invasively monitor the longitudinal distribution of both proteins. RESULTS: (131)I-IFN-alpha-Fc was shown to have higher stability than (131)I-IFN-alpha in whole blood, plasma, kidney, liver and stomach from the biodistribution study. The area under curve analyzed from plasma in the phomacokinetics study was 10 fold higher for (131)I-IFN-alpha-Fc than for (131)I-IFN-alpha. At 0-1 h post tail vein injection, both labelled proteins are mainly accumulated in the kidneys and liver. Notably, (131)I-IFN-alpha-Fc is degraded more slowly than (131)I-IFN alpha. CONCLUSION: We demonstrated that (131)I-IFN-alpha-Fc has longer blood circulation time and better biostability than (131)I-IFN-alpha, suggesting the potential application of the immunoglobulin Fc-conjugated cytokine for long-term treatment of diseases. PMID- 26130790 TI - Ethanol Extract of Hedyotis diffusa Willd Affects Immune Responses in Normal Balb/c Mice In Vivo. AB - Numerous clinical anticancer drugs are obtained from natural plants and Hedyotis diffusa Willd (EEHDW) has been used as a major component in Traditional Chinese medicine formulas since a long time. Ethanol extracts of EEHDW have been shown to possess various biological activities including anticancer function in vitro. Our earlier studies have shown that EEHDW affects immune responses in WEHI-3 generated leukemia mice, but EEHDW has not been reported to affect immune responses in a normal mouse model. Herein, we investigated whether EEHDW could affect immune responses on normal murine cells in vivo. Normal BALB/c mice were orally treated with or without EEHDW at 0, 16, 32, and 64 mg/kg or 32 mg/kg by i.p. for 3 weeks, then were weighed, and blood, liver and spleen samples were collected for further experiments. Results indicated that EEHDW did not significantly affect body and liver weight but significantly increased the spleen weight by i.p. treatment when compared to control groups. Flow cytometric assays indicated that EEHDW promoted CD11b levels at 16, 32 and 64 mg/kg oral treatment, CD19 levels at 16, 32, 64 mg/kg oral treatment and i.p. treatment, and Mac-3 levels at 16, 32 and 64 mg/kg oral treatment, however, it did not significantly affect the levels of CD3. Oral treatment with 16 and 32 mg/kg of EEHDW significantly decreased macrophage phagocytosis from PBMC; 32 mg/kg of EEHDW by i.p. treatment significantly increased phagocytosis activity of macrophages obtain from the peritoneal cavity. EEHDW at 32 mg/kg by i.p. treatment led to an increase of NK cell activities compared to oil control groups. EEHDW at 32 mg/kg of EEHDW by i.p. treatment increased B- and T-cell proliferation. Based on these observations, EEHDW seems to have promoted immune responses in this murine model. PMID- 26130791 TI - Polymorphisms of MMP9 and TIMP2 in Patients with Varicose Veins. AB - BACKGROUND: Genetic predisposition is a suggested risk factor in the etiology of varicose veins. The matrix metalloproteinase (MMP) family degrades extracellular matrix (ECM) and may lead to disturbances in vein wall structure. The activity of MMPs in the ECM are controlled by specific tissue inhibitors of MMPs (TIMP). The present study aimed to investigate the relationship between MMP9 and TIMP2 gene polymorphisms and varicose vein risk. MATERIALS AND METHODS: Genotyping of the polymorphisms of MMP9 (1562 C/T) and TIMP2 (418G/C) was performed using polymerase chain reaction and restriction-fragment length polymorphism assays in a group of patients with varicose veins (n=63) and healthy controls (n=70). RESULTS: The frequencies of MMP9 alleles and genotypes did not differ significantly between patient and control groups. However, TIMP2 -418 C allele was associated with increased risk for varicose vein formation (p=0.007). It was also shown that the frequency of the GG genotype was significantly higher in the control group than in the patient group (odds ratio=0.333, 95% confidence interval=0.14-0.78, p=0.012). CONCLUSION: TIMP2 -418 C allele is associated with susceptibility for varicose vein formation and individuals with GG genotype may have a lower risk for varicose vein formation. PMID- 26130792 TI - The Nasopalatine Canal in Adults on Cone Beam Computed Tomograms-A Clinical Study and Review of the Literature. AB - AIM: The aims of this study were to assess the location, morphology and anatomical dimensions of the nasopalatine canal (NPC) on cone beam computed tomographic (CBCT) images and to compare our findings with recent reports on this matter. A detailed knowledge of anatomical variations is mandatory in skeletal surgery of the anterior maxilla. PATIENTS AND METHODS: Two hundred CBCT scans of the mid-facial region were analyzed from adult patients at the Outpatient Clinic of the Department of Oral and Craniomaxillofacial Surgery, University of Hamburg, Germany. Patients were scanned using standard exposure time at normal patient positioning inside the CBCT device. Three-dimensional (3D) CBCT images were carefully analyzed regarding NPC location, morphology and anatomical dimensions, and variations of radiological morphology, with respect to age and gender. RESULTS: In the sagittal plane, the NPC typically appeared as a canal with a mean length+/-standard deviation (SD) of 11.15+/-2.87 mm. The oral cavity opening of the canal is the incisive foramen, with a mean diameter of 4.49+/-1.71 mm. At the entrance to the nasal floor, in most cases, two apertures were found (Y-canal morphology), but also three or four openings were observed. In particular cases, the canal presented a cylindrical aperture with only one exit to the nasal floor. The average width of the NPC at the level of the nasal floor was 3.43+/-1.54 mm. The labiopalatal width of the NPC measured perpendicular to the long axis of the canal on sagittal plane was 2.48+/-1.33 mm. Interpretation of NPC morphology was significantly different when analyzing the images in the sagittal plane only, but the technique allowed demonstration of all aspects using the combined 2D/3D interpretation. CONCLUSION: The NPC may exhibit important anatomical variations, both with regard to morphology and its dimensions. To avoid any potential complications during dentoalveolar surgery, careful preoperative evaluation is required. 3D imaging is recommended to determine canal topography and dimensions, and to assess the individual anterior maxilla's dimensions prior to surgical procedures, such as dental implant insertion or bone augmentation. PMID- 26130793 TI - Diagnostic Performance of Left Atrial Diameter Measurement in Computed Tomography to Detect Increased Left Atrial Volume. AB - BACKGROUND/AIM: The left atrium (LA) is frequently imaged in cardiac computed tomographic (cCT) examinations. The LA volume can be accurately measured with three-dimensional (3D) volumetry but this method is time consuming and thus not routinely used in clinical practice. Accordingly, increased LA size may be overlooked although volume enlargement is associated with adverse cardiovascular events. We evaluated the accuracy of LA diameter measurement in cCT and in transthoracic echocardiography (TTE) in the diagnosis of LA enlargement using 3D cCT as the reference standard. PATIENTS AND METHODS: Altogether, 146 patients with suspected cardiogenic stroke underwent cCT and TTE. LA volume by cCT was determined for all patients. LA diameter was measured in both modalities. Furthermore, 40 healthy controls were analyzed in order to assess the cut-off values for normal LA volume. Diagnostic performance of cCT and conventional TTE diametrical measurements for detecting enlarged LA volume were analyzed and compared using Cohen's kappa (kappa). RESULTS: In controls, the mean LA volume was 59.8+/-15.3 ml and the mean LA diameter was 30.4+/-5.0 mm by cCT. The mean value plus twice the standard deviation, which was considered the upper limit, for normal LA volume and diameter were 90.4 ml and 40.4 mm, respectively. Age- and gender-matched patients with stroke had statistically significantly (p<0.001) larger LA volumes (85.5+/-21.1 vs. 59.8+/-15.3 ml) and diameters (37.6+/-5.7 vs. 30.4+/-5.0 mm) than controls. LA diameter measurement by cCT was more reliable in detecting an LA volume enlargement than the corresponding measurement with TTE (kappa=0.489 vs. 0.234; p=0.002). CONCLUSION: An enlarged LA diameter measured by cCT was more reliable than TTE at detecting enlarged LA volume. PMID- 26130794 TI - Laparoscopic Totally Extraperitoneal Inguinal Hernia Repair in the Elderly: A Prospective Control Study. AB - Inguinal hernia (IH) repair can be obtained with both open and laparoscopic techniques, which are usually performed using a transabdominal preperitoneal (TAPP) or a totally extraperitoneal (TEP) approach. The aim of the study was to evaluate whether the results of laparoscopic TEP IH repair in the elderly (>=65 years old) are different with respect to results obtained in younger patients. One hundred and four consecutive patients (four women and 100 men, median age of 57 years, range=21-85 years) with unilateral (N=21, 20.2%) or bilateral (N=83, 79.8%) IH were prospectively enrolled in the study. Patients were divided into two groups according to their age: group A (N=68, 65.4%) aged <65 years and group B (N=36, 34.6%) aged >=65 years. The mean operative time was not significantly different between groups (48+/-20 vs. 52+/-20 min, p=0.33). One case of increased PaCO2 was observed in each group (p=0.72) and two and one case of pneumoperitoneum (p=0.57) in groups A and B, respectively. Two (1.9%) patients (one in each group; p=0.55) required TEP conversion. Mild postoperative complications developed in four patients of each group (p=0.44). After one-year follow-up, three (2.9%) recurrences occurred (group 1=1, group 2=2, p=0.55), both in patients who had undergone direct IH repair. The overall postoperative relative risk of complications related to age was 1.08 (95% confidence interval=0.91-1.27, p=0.53). In conclusion, our results suggest that in patients with IH scheduled for TEP repair, age does not represent a contraindication to surgery in terms of complication rate and postoperative results. PMID- 26130795 TI - Evidence of Subcutaneous Tissue Lipolysis Enhancement by Endogenous Cortisol in Critically Ill Patients Without Shock. AB - BACKGROUND/AIM: Cortisol is involved in in many aspects of adipose tissue metabolism. A positive association between plasma cortisol and lipolysis has been observed. Critically ill patients exhibit 'lipemia of sepsis'. The aim of the present study was to study, in septic ICU patients, adipose tissue lipolysis in relation to tissue cortisol using microdialysis (MD). PATIENTS AND METHODS: We studied 17 mechanically-ventilated patients (9 men; mean+/-SD age=63+/-19 years) with a diagnosis of severe sepsis. Upon ICU admission, an MD catheter was inserted under sterile conditions into the subcutaneous adipose tissue of the upper thigh. On days 2, 3 and 4, MD samples were collected six times per day for glycerol (used as an index of lipolysis) and tissue cortisol determinations. The mean of these six collections was used for analysis (normal values for adipose tissue glycerol <200 MUmol/l). Statistics were carried-out with analysis of covariance (ANCOVA) and linear regression. RESULTS: More than half of the samplings (19/31) indicated accentuated lipolysis with above-normal MD glycerol levels. By ANCOVA, MD glycerol (log values) was associated with MD cortisol (log values) (p=0.012) and was not associated with age or day of sampling. Furthermore, MD glycerol (log values) was positively correlated to MD cortisol (log values) (r=0.490, p=0.012). DISCUSSION: Changes in interstitial/tissue cortisol may not be reflected in (total) plasma cortisol concentration. Thus, it is interesting that we observed, albeit weak, an association between tissue lipolysis (via MD glycerol levels) and MD cortisol, verifying (although modestly so) the well-known association between lipolysis and cortisol. PMID- 26130797 TI - Adherence to the Mediterranean diet by the Greek and Cypriot population: a systematic review. AB - BACKGROUND: The traditional Mediterranean diet is defined as the dietary pattern in the countries of the Mediterranean basin between the 1950s and 1960s, and it is now widely accepted that has a beneficial effect on health. A debate exists from empirical and research data if the traditional Mediterranean diet remains the main dietary pattern of the region or if it has changed overtime. AIMS: This systematic review addresses whether the people of Cyprus and Greece still follow the traditional Mediterranean diet or whether the diet has become more 'Westernised'. METHODS: The MEDLINE database was searched using relevant free terms and independently reviewed by two authors. In addition, all reference lists of identified studies were hand-searched to identify additional, relevant studies. RESULTS: The review resulted in 18 research papers that met the inclusion and exclusion criteria and represented 15 independent studies. The main outcome was consistent between studies and indicated moderate adherence of the Greek, and (probably) of the Cypriot, population to the Mediterranean diet. The majority of studies found no statistically significant differences by gender. There was an observed inter-study lower adherence to the Mediterranean diet by the younger population. Few studies addressed intra-study variations by age. CONCLUSIONS: This review shows that adherence to the Mediterranean diet is moderate in Greece (and probably also in Cyprus).This suggests a continuing transition from dietary patterns in the 50 s-60 s towards a more Westernized diet. PMID- 26130796 TI - Evaluation of Intracranial Cerebral Blood Flow Velocities in Splenectomised and Non-Splenectomised Patients with beta-Thalassemia Intermedia Using Transcranial Doppler Sonography. AB - BACKGROUND: A high incidence of clinically-silent cerebral ischemic events has been reported in splenectomised patients with beta-thalassemia intermedia (betaTI). These could be due to cerebral large-vessel disease. Based on the example of sickle cell disease, we applied transcranial Doppler sonography (TCD) to evaluate cerebral vessels velocity as a possible indicator of cerebral vasculopathy. PATIENTS AND METHODS: In our study, we included 17 splenectomised and 13 non-splenectomised (control group) patients with betaTI. Non-imaging TCD was performed and the time-averaged mean velocity (TAMV) values of cerebral arteries were measured. RESULTS: There was no statistically significant difference between the two groups concerning age, gender, hemoglobin and hematocrit levels, nor in the TAMV values for all examined vessels (p>0.05). A statistically significant difference was found in platelet count (PLT) (p<0.01) that was higher in splenectomised patients. CONCLUSION: Our results do not support the presence of large-vessel vasculopathy in splenectomised betaTI patients and agree with recent studies reporting that cerebral ischemic events in these patients might be due to microangiopathy or venous thromboembolism. PMID- 26130798 TI - Determinants of attaining and maintaining a low cardiovascular risk profile--the Doetinchem Cohort Study. AB - BACKGROUND: While maintenance of a low cardiovascular risk profile is essential for cardiovascular disease (CVD) prevention, few people maintain a low CVD risk profile throughout their life. We studied the association of demographic, lifestyle, psychological factors and family history of CVD with attainment and maintenance of a low risk profile over three subsequent 5-year periods. METHODS: Measurements of 6390 adults aged 26-65 years at baseline were completed from 1993 to 97 and subsequently at 5-year intervals until 2013. At each wave, participants were categorized into low risk profile (ideal levels of blood pressure, cholesterol and body mass index, non-smoking and no diabetes) and medium/high risk profile (all others). Multivariable-adjusted modified Poisson regression analyses were used to examine determinants of attainment and maintenance of low risk; risk ratios (RR) and 95% confidence intervals (95% CI) were obtained. Generalized estimating equations were used to combine multiple 5-year comparisons. RESULTS: Younger age, female gender and high educational level were associated with higher likelihood of both maintaining and attaining low risk profile (P < 0.05). In addition, likelihood of attaining low risk was 9% higher with each 1-unit increment in Mediterranean diet score (RR: 1.09, 95% CI: 1.02 1.16), twice as high with any physical activity versus none (RR: 2.17, 95% CI: 1.16-4.04) and 35% higher with moderate alcohol consumption versus heavy consumption (RR: 1.35, 95% CI: 1.06-1.73). CONCLUSION: Healthy lifestyle factors such as adherence to a Mediterranean diet, physical activity and moderate as opposed to heavy alcohol consumption were associated with a higher likelihood of attaining a low risk profile. PMID- 26130799 TI - Discovering the first tyrosine kinase. AB - In the middle of the 20th century, animal tumor viruses were heralded as possible models for understanding human cancer. By the mid-1970s, the molecular basis by which tumor viruses transform cells into a malignant state was beginning to emerge as the first viral genomic sequences were reported and the proteins encoded by their transforming genes were identified and characterized. This was a time of great excitement and rapid progress. In 1978, prompted by the discovery from Ray Erikson's group that the Rous sarcoma virus (RSV) v-Src-transforming protein had an associated protein kinase activity specific for threonine, my group at the Salk Institute set out to determine whether the polyomavirus middle T-transforming protein had a similar kinase activity. Here, I describe the experiments that led to the identification of a kinase activity associated with middle T antigen and our serendipitous discovery that this activity was specific for tyrosine in vitro, and how this in turn led to the fortuitous observation that the v-Src-associated kinase activity was also specific for tyrosine. Our finding that v-Src increased the level of phosphotyrosine in cellular proteins in RSV-transformed cells confirmed that v-Src is a tyrosine kinase and transforms cells by phosphorylating proteins on tyrosine. My colleague Bart Sefton and I reported these findings in the March issue of PNAS in 1980. Remarkably, all of the experiments in this paper were accomplished in less than one month. PMID- 26130800 TI - News Feature: The cells that flock together. PMID- 26130801 TI - Inner Workings: Tyrosine kinases, their discovery and impact. PMID- 26130803 TI - Coarse-grained simulations of bacterial cell wall growth reveal that local coordination alone can be sufficient to maintain rod shape. AB - Bacteria are surrounded by a peptidoglycan (PG) cell wall that must be remodeled to allow cell growth. While many structural details and properties of PG and the individual enzymes involved are known, how the process is coordinated to maintain cell integrity and rod shape is not understood. We have developed a coarse grained method to simulate how individual transglycosylases, transpeptidases, and endopeptidases could introduce new material into an existing unilayer PG network. We find that a simple model with no enzyme coordination fails to maintain cell wall integrity and rod shape. We then iteratively analyze failure modes and explore different mechanistic hypotheses about how each problem might be overcome by the macromolecules involved. In contrast to a current theory, which posits that long MreB filaments are needed to coordinate PG insertion sites, we find that local coordination of enzyme activities in individual complexes can be sufficient to maintain cell integrity and rod shape. We also present possible molecular explanations for the existence of monofunctional transpeptidases and glycosidases (glycoside hydrolases), trimeric peptide crosslinks, cell twisting during growth, and synthesis of new strands in pairs. PMID- 26130804 TI - GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time. AB - The mammalian suprachiasmatic nucleus (SCN) forms not only the master circadian clock but also a seasonal clock. This neural network of ~10,000 circadian oscillators encodes season-dependent day-length changes through a largely unknown mechanism. We show that region-intrinsic changes in the SCN fine-tune the degree of network synchrony and reorganize the phase relationship among circadian oscillators to represent day length. We measure oscillations of the clock gene Bmal1, at single-cell and regional levels in cultured SCN explanted from animals raised under short or long days. Coupling estimation using the Kuramoto framework reveals that the network has couplings that can be both phase-attractive (synchronizing) and -repulsive (desynchronizing). The phase gap between the dorsal and ventral regions increases and the overall period of the SCN shortens with longer day length. We find that one of the underlying physiological mechanisms is the modulation of the intracellular chloride concentration, which can adjust the strength and polarity of the ionotropic GABAA-mediated synaptic input. We show that increasing day-length changes the pattern of chloride transporter expression, yielding more excitatory GABA synaptic input, and that blocking GABAA signaling or the chloride transporter disrupts the unique phase and period organization induced by the day length. We test the consequences of this tunable GABA coupling in the context of excitation-inhibition balance through detailed realistic modeling. These results indicate that the network encoding of seasonal time is controlled by modulation of intracellular chloride, which determines the phase relationship among and period difference between the dorsal and ventral SCN. PMID- 26130805 TI - Distinct roles for GABA across multiple timescales in mammalian circadian timekeeping. AB - The suprachiasmatic nuclei (SCN), the central circadian pacemakers in mammals, comprise a multiscale neuronal system that times daily events. We use recent advances in graphics processing unit computing to generate a multiscale model for the SCN that resolves cellular electrical activity down to the timescale of individual action potentials and the intracellular molecular events that generate circadian rhythms. We use the model to study the role of the neurotransmitter GABA in synchronizing circadian rhythms among individual SCN neurons, a topic of much debate in the circadian community. The model predicts that GABA signaling has two components: phasic (fast) and tonic (slow). Phasic GABA postsynaptic currents are released after action potentials, and can both increase or decrease firing rate, depending on their timing in the interspike interval, a modeling hypothesis we experimentally validate; this allows flexibility in the timing of circadian output signals. Phasic GABA, however, does not significantly affect molecular timekeeping. The tonic GABA signal is released when cells become very excited and depolarized; it changes the excitability of neurons in the network, can shift molecular rhythms, and affects SCN synchrony. We measure which neurons are excited or inhibited by GABA across the day and find GABA-excited neurons are synchronized by-and GABA-inhibited neurons repelled from-this tonic GABA signal, which modulates the synchrony in the SCN provided by other signaling molecules. Our mathematical model also provides an important tool for circadian research, and a model computational system for the many multiscale projects currently studying brain function. PMID- 26130806 TI - Structural characterization of the interaction of Ubp6 with the 26S proteasome. AB - In eukaryotic cells, the 26S proteasome is responsible for the regulated degradation of intracellular proteins. Several cofactors interact transiently with this large macromolecular machine and modulate its function. The deubiquitylating enzyme ubiquitin C-terminal hydrolase 6 [Ubp6; ubiquitin specific protease (USP) 14 in mammals] is the most abundant proteasome interacting protein and has multiple roles in regulating proteasome function. Here, we investigate the structural basis of the interaction between Ubp6 and the 26S proteasome in the presence and absence of the inhibitor ubiquitin aldehyde. To this end we have used single-particle electron cryomicroscopy in combination with cross-linking and mass spectrometry. Ubp6 binds to the regulatory particle non-ATPase (Rpn) 1 via its N-terminal ubiquitin-like domain, whereas its catalytic USP domain is positioned variably. Addition of ubiquitin aldehyde stabilizes the binding of the USP domain in a position where it bridges the proteasome subunits Rpn1 and the regulatory particle triple-A ATPase (Rpt) 1. The USP domain binds to Rpt1 in the immediate vicinity of the Ubp6 active site, which may effect its activation. The catalytic triad is positioned in proximity to the mouth of the ATPase module and to the deubiquitylating enzyme Rpn11, strongly implying their functional linkage. On the proteasome side, binding of Ubp6 favors conformational switching of the 26S proteasome into an intermediate-energy conformational state, in particular upon the addition of ubiquitin aldehyde. This modulation of the conformational space of the 26S proteasome by Ubp6 explains the effects of Ubp6 on the kinetics of proteasomal degradation. PMID- 26130808 TI - Correction for Sullivan et al., Spatially robust estimates of biological nitrogen (N) fixation imply substantial human alteration of the tropical N cycle. PMID- 26130807 TI - Delicate conformational balance of the redox enzyme cytochrome P450cam. AB - The energy landscapes of proteins are highly complex and can be influenced by changes in physical and chemical conditions under which the protein is studied. The redox enzyme cytochrome P450cam undergoes a multistep catalytic cycle wherein two electrons are transferred to the heme group and the enzyme visits several conformational states. Using paramagnetic NMR spectroscopy with a lanthanoid tag, we show that the enzyme bound to its redox partner, putidaredoxin, is in a closed state at ambient temperature in solution. This result contrasts with recent crystal structures of the complex, which suggest that the enzyme opens up when bound to its partner. The closed state supports a model of catalysis in which the substrate is locked in the active site pocket and the enzyme acts as an insulator for the reactive intermediates of the reaction. PMID- 26130810 TI - Supercooled spin liquid state in the frustrated pyrochlore Dy2Ti2O7. AB - A "supercooled" liquid develops when a fluid does not crystallize upon cooling below its ordering temperature. Instead, the microscopic relaxation times diverge so rapidly that, upon further cooling, equilibration eventually becomes impossible and glass formation occurs. Classic supercooled liquids exhibit specific identifiers including microscopic relaxation times diverging on a Vogel Tammann-Fulcher (VTF) trajectory, a Havriliak-Negami (HN) form for the dielectric function epsilon(omega, T), and a general Kohlrausch-Williams-Watts (KWW) form for time-domain relaxation. Recently, the pyrochlore Dy2Ti2O7 has become of interest because its frustrated magnetic interactions may, in theory, lead to highly exotic magnetic fluids. However, its true magnetic state at low temperatures has proven very difficult to identify unambiguously. Here, we introduce high precision, boundary-free magnetization transport techniques based upon toroidal geometries and gain an improved understanding of the time- and frequency-dependent magnetization dynamics of Dy2Ti2O7. We demonstrate a virtually universal HN form for the magnetic susceptibility chi (omega, T), a general KWW form for the realtime magnetic relaxation, and a divergence of the microscopic magnetic relaxation rates with the VTF trajectory. Low-temperature Dy2Ti2O7 therefore exhibits the characteristics of a supercooled magnetic liquid. One implication is that this translationally invariant lattice of strongly correlated spins may be evolving toward an unprecedented magnetic glass state, perhaps due to many-body localization of spin. PMID- 26130811 TI - Cardiac sarcoidosis: diagnosis and management. AB - Cardiac sarcoidosis is one of the most serious and unpredictable aspects of this disease state. Heart involvement frequently presents with arrhythmias or conduction disease, although myocardial infiltration resulting in congestive heart failure may also occur. The prognosis in cardiac sarcoidosis is highly variable, which relates to the heterogeneous nature of heart involvement and marked differences between racial groups. Electrocardiography and echocardiography often provide the first clue to the diagnosis, but advanced imaging studies using positron emission tomography and MRI, in combination with nuclear isotope perfusion scanning are now essential to the diagnosis and management of this condition. The identification of clinically occult cardiac sarcoidosis and the management of isolated and/or asymptomatic heart involvement remain both challenging and contentious. Corticosteroids remain the first treatment choice with the later substitution of immunosuppressive and steroid sparing therapies. Heart transplantation is an unusual outcome, but when performed, the results are comparable or better than heart transplantation for other disease states. We review the epidemiology, developments in diagnostic techniques and the management of cardiac sarcoidosis. PMID- 26130809 TI - Novel protein Callipygian defines the back of migrating cells. AB - Asymmetric protein localization is essential for cell polarity and migration. We report a novel protein, Callipygian (CynA), which localizes to the lagging edge before other proteins and becomes more tightly restricted as cells polarize; additionally, it accumulates in the cleavage furrow during cytokinesis. CynA protein that is tightly localized, or "clustered," to the cell rear is immobile, but when polarity is disrupted, it disperses throughout the membrane and responds to uniform chemoattractant stimulation by transiently localizing to the cytosol. These behaviors require a pleckstrin homology-domain membrane tether and a WD40 clustering domain, which can also direct other membrane proteins to the back. Fragments of CynA lacking the pleckstrin homology domain, which are normally found in the cytosol, localize to the lagging edge membrane when coexpressed with full-length protein, showing that CynA clustering is mediated by oligomerization. Cells lacking CynA have aberrant lateral protrusions, altered leading-edge morphology, and decreased directional persistence, whereas those overexpressing the protein display exaggerated features of polarity. Consistently, actin polymerization is inhibited at sites of CynA accumulation, thereby restricting protrusions to the opposite edge. We suggest that the mutual antagonism between CynA and regions of responsiveness creates a positive feedback loop that restricts CynA to the rear and contributes to the establishment of the cell axis. PMID- 26130812 TI - Transdural spinal cord herniation with extradural cerebrospinal fluid collection. PMID- 26130813 TI - How can healthcare standards be standardised? AB - International travel, medical tourism and trade have created a demand for reliable assessment of healthcare provision across borders, and for information which is accessible to patients, insurers and referring institutions. External assessment schemes for healthcare providers may be clustered into three types: statutory regulation and institutional licensing, International Standardization Organisation certification, and voluntary systems such as peer review and healthcare accreditation. Increasing complexity of healthcare provision, pressures for public accountability and expectations of professional self governance place a burden on the inspectors and the inspected. If only to contain costs of external assessment and to increase access to reliable information for patients and insurers, the three approaches must work together rather than compete. This paper summarises the origins, aims, authority and methods of the three general models, describing current pressures and opportunities for convergence (between systems and across borders) in the UK and in Europe. PMID- 26130814 TI - Oncofertility: a grand collaboration between reproductive medicine and oncology. AB - In 2007, I was asked by the University of Calgary to participate in a symposium called 'Pushing the Boundaries--Advances that Will Change the World in 20 Years'. My topic was oncofertility, a word I had just coined to describe the intersection of two disciplines--oncology and fertility--and I was thrilled to share my passion for this new field and help young women with cancer protect their future reproductive health. Fertility preservation in the cancer setting lacked a concerted effort to bridge the disciplines in an organized manner. In early 2015, I was delighted to deliver a presentation for the Society for Reproduction and Fertility titled 'Sex in Three Cities', where I gave an update on the oncofertility movement, a remarkable cross-disciplinary, global collaboration created to address the fertility preservation needs of young cancer patients. During my tour of the UK, I was impressed by the interest among the society and its members to engage colleagues outside the discipline as well as the public in a dialogue about cutting-edge reproductive science. In this invited review, I will describe the work of the Oncofertility Consortium to provide fertility preservation options in the cancer setting and accelerate the acceptance of this critical topic on a global scale. I hope that one day this word and field it created will change the world for women who had been left out of the equation for far too long. PMID- 26130816 TI - Hot Topics in Noninvasive Ventilation: Report of a Working Group at the International Symposium on Sleep-Disordered Breathing in Leuven, Belgium. AB - During the last few decades, attention has increasingly focused on noninvasive ventilation (NIV) in the treatment of chronic respiratory failure. The University of Leuven and the University Hospitals Leuven therefore chose this topic for a 2 day working group session during their International Symposium on Sleep Disordered Breathing. Numerous European experts took part in this session and discussed (1) NIV in amyotrophic lateral sclerosis (when to start NIV, NIV and sleep, secretion management, and what to do when NIV fails), (2) recent insights in NIV and COPD (high-intensity NIV, NIV in addition to exercise training, and NIV during exercise training), (3) monitoring of NIV (monitoring devices, built in ventilator software, leaks, and asynchronies) and identifying events during NIV; and (4) recent and future developments in NIV (target-volume NIV, electromyography-triggered NIV, and autoregulating algorithms). PMID- 26130815 TI - The role of WNT signaling in adult ovarian folliculogenesis. AB - Wingless-type mouse mammary tumor virus integration site (WNT) signaling molecules are locally secreted glycoproteins that play important role in regulation of ovarian follicle maturation and steroid production. Components of the WNT signaling pathway have been demonstrated to impact reproductive functions, including embryonic development of the sex organs and regulation of follicle maturation controlling steroidogenesis in the postnatal ovary. Emerging evidence underscores the complexity of WNT signaling molecules in regulation of dynamic changes that occur in the ovary during the reproductive cycle. While disruption in the WNT signaling cascade has been recognized to have deleterious consequences to normal sexual development, more recent studies are beginning to highlight the importance of these molecules in adult ovarian function related to follicle development, corpus luteum formation, steroid production and fertility. Hormonal regulation of WNT genes and expression of members of the WNT signaling network, including WNT ligands, frizzled receptors, and downstream signaling components that are expressed in the postnatal ovary at distinct stages of the estrous cycle suggest a crucial role in normal ovarian function. Similarly, FSH stimulation of T-cell factor-dependent gene expression requires input from beta catenin, a lynchpin molecule in canonical WNT signaling, further indicating beta catenin participation in regulation of follicle maturation. This review will focus on the multiple functions of WNT signaling in folliculogenesis in the adult ovary. PMID- 26130817 TI - Variation in Medicare Payments for Colorectal Cancer Surgery. AB - PURPOSE: Colorectal cancer (CRC) is the second most expensive cancer in the United States. Episode-based bundled payments may be a strategy to decrease costs. However, it is unknown how payments are distributed across hospitals and different perioperative services. METHODS: We extracted actual Medicare payments for patients in the fee-for-service Medicare population who underwent CRC surgery between January 2004 and December 2006 (N = 105,016 patients). Payments included all service types from the date of hospitalization up to 1 year later. Hospitals were ranked from least to most expensive and grouped into quintiles. Results were case-mix adjusted and price standardized using empirical Bayes methods. We assessed the contributions of index hospitalization, physician services, readmissions, and postacute care to the overall variation in payment. RESULTS: There is wide variation in total payments for CRC care within the first year after CRC surgery. Actual Medicare payments were $51,345 per patient in the highest quintile and $26,441 per patient in the lowest quintile, representing a difference of Delta = $24,902. Differences were persistent after price standardization (Delta = $17,184 per patient) and case-mix adjustment (Delta = $4,790 per patient). Payments for the index surgical hospitalization accounted for the largest share (65%) of payments but only minimally varied (11.6%) across quintiles. However, readmissions and postacute care services accounted for substantial variations in total payments. CONCLUSION: Medicare spending in the first year after CRC surgery varies across hospitals even after case-mix adjustment and price standardization. Variation is largely driven by postacute care and not the index surgical hospitalization. This has significant implications for policy decisions on how to bundle payments and define episodes of surgical CRC care. PMID- 26130818 TI - Improving Patient Satisfaction in a Midsize Pediatric Hematology-Oncology Outpatient Clinic. AB - PURPOSE: The study of patient satisfaction is a rapidly emerging area of importance within health care. High levels of patient satisfaction are associated with exceptional physician-patient communication, superior patient compliance, reduced risk of medical malpractice, and economic benefit in the value-based purchasing era. To our knowledge, no previous reports have evaluated methods to improve the patient experience within the pediatric hematology-oncology (PHO) outpatient clinic. METHODS: Patient satisfaction was measured using returned Press-Ganey surveys at Blank Children's Hospital PHO outpatient clinic (UnityPoint Health). The aim of this study was to raise the overall patient satisfaction score to the 75th percentile and raise the care provider score (CP) to the 90th percentile nationally. After analyzing data from 2013, interventions were implemented in January 2014, including weekly review of returned surveys, review of goals and progress at monthly staff meetings, distribution of written materials addressing deficiencies, score transparency among providers, provider use of Web-based patient satisfaction training modules, devotion of additional efforts to address less satisfied demographics (new patient consultations), and more liberal use of service recovery techniques. RESULTS: In the PHO outpatient clinic, overall patient satisfaction improved from the 56th to 97th percentile. Care provider scores improved from the 70th to 99 th percentile. For new patients, overall satisfaction improved from the 27th to 92 nd percentile, and care provider scores improved from the 29th to 98 th percentile. CONCLUSION: Patient satisfaction was improved in a midsize PHO clinic by implementing provider- and staff-driven initiatives. A combination of minor behavioral changes among care providers and staff in conjunction with systems-related modifications drove improvement. PMID- 26130819 TI - Bridging the Medical Education and Quality Cancer Care Divide: A Call to Action. PMID- 26130820 TI - The integration of facial and vocal cues during emotional change perception: EEG markers. AB - The ability to detect emotional changes is of primary importance for social living. Though emotional signals are often conveyed by multiple modalities, how emotional changes in vocal and facial modalities integrate into a unified percept has yet to be directly investigated. To address this issue, we asked participants to detect emotional changes delivered by facial, vocal and facial-vocal expressions while behavioral responses and electroencephalogram were recorded. Behavioral results showed that bimodal emotional changes were detected with higher accuracy and shorter response latencies compared with each unimodal condition. Moreover, the detection of emotional change, regardless of modalities, was associated with enhanced amplitudes in the N2 and P3 component, as well as greater theta synchronization. More importantly, the P3 amplitudes and theta synchronization were larger for the bimodal emotional change condition than for the sum of the two unimodal conditions. The superadditive responses in P3 amplitudes and theta synchronization were both positively correlated with the magnitude of the bimodal superadditivity in accuracy. These behavioral and electrophysiological data consistently illustrated an effect of audiovisual integration during the detection of emotional changes, which is most likely mediated by the P3 activity and theta oscillations in brain responses. PMID- 26130822 TI - Diversifying selection by Desmodiinae legume species on Bradyrhizobium symbionts. AB - Desmodium and Hylodesmum (Papilionoideae Subtribe Desmodiinae) are among the most common herbaceous perennial legumes native to eastern North America. To analyze the population structure of their Bradyrhizobium sp. root-nodule bacteria, 159 isolates were sampled from ten host species across a 1000 km region. Phylogenetic analysis of four housekeeping loci (2164 bp) and two loci in the symbiosis island (SI) chromosomal region (1374 bp) indicated extensive overlap in symbiont utilization, with each common bacterial clade found on 2-7 species of these legume genera. However, host species differed considerably in the relative proportion of symbionts belonging to different Bradyrhizobium clades. High phylogenetic incongruence between trees for housekeeping loci and SI loci suggested that diversification of these Bradyrhizobium lineages involved substantial horizontal gene transfer. Plant inoculation with strains from six Bradyrhizobium clades revealed marked disparity in relative bacterial reproductive success across four Desmodium species. Estimated yield of Bradyrhizobium progeny cells per plant ranged from zero to >10(9), and strains with high fitness on one host sometimes reproduced poorly on other host species. Diversifying selection on bacteria, arising from differential success in habitats with different Desmodium and Hylodesmum taxa, is therefore likely to affect Bradyrhizobium diversity patterns at the landscape level. PMID- 26130823 TI - A retrospective metagenomics approach to studying Blastocystis. AB - Blastocystis is a common single-celled intestinal parasitic genus, comprising several subtypes. Here, we screened data obtained by metagenomic analysis of faecal DNA for Blastocystis by searching for subtype-specific genes in coabundance gene groups, which are groups of genes that covary across a selection of 316 human faecal samples, hence representing genes originating from a single subtype. The 316 faecal samples were from 236 healthy individuals, 13 patients with Crohn's disease (CD) and 67 patients with ulcerative colitis (UC). The prevalence of Blastocystis was 20.3% in the healthy individuals and 14.9% in patients with UC. Meanwhile, Blastocystis was absent in patients with CD. Individuals with intestinal microbiota dominated by Bacteroides were much less prone to having Blastocystis-positive stool (Matthew's correlation coefficient = 0.25, P < 0.0001) than individuals with Ruminococcus- and Prevotella-driven enterotypes. This is the first study to investigate the relationship between Blastocystis and communities of gut bacteria using a metagenomics approach. The study serves as an example of how it is possible to retrospectively investigate microbial eukaryotic communities in the gut using metagenomic datasets targeting the bacterial component of the intestinal microbiome and the interplay between these microbial communities. PMID- 26130821 TI - BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year. AB - Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs. PMID- 26130824 TI - Single-shot nuclear magnetization recovery curves with force-gradient detection. AB - We measure the spin-lattice relaxation time as a function of sample temperature in GaAs in a real-time single-shot inversion recovery experiment using spin force gradients acting on a magnetic tipped cantilever. After inverting 69Ga spins localized near the magnet with a single 20 ms adiabatic rapid passage sweep, the spins' magnetization recovery was passively tracked by recording the cantilever's frequency change, which is proportional to the longitudinal component of the spins' magnetization. The cantilever's frequency was recorded for a time 3*T1 for sample temperatures ranging from 4.8 to 25 K. The temperature dependence was observed for the 69Ga quadrupolar relaxation interaction. PMID- 26130825 TI - Analysis of the effects of curvature and thickness on elastic wave velocity in cornea-like structures by finite element modeling and optical coherence elastography. AB - Wave models that have been used to extract the biomechanical properties of the cornea from the propagation of an elastic wave are based on an assumption of thin plate geometry. However, this assumption does not account for the effects of corneal curvature and thickness. This study conducts finite element (FE) simulations on four types of cornea-like structures as well as optical coherence elastography (OCE) experiments on contact lenses and tissue-mimicking phantoms to investigate the effects of curvature and thickness on the group velocity of an elastic wave. The elastic wave velocity as determined by FE simulations and OCE of a spherical shell section decreased from ~2.8 m/s to ~2.2 m/s as the radius of curvature increased from 19.1 mm to 47.7 mm and increased from ~3.0 m/s to ~4.1 m/s as the thickness of the agar phantom increased from 1.9 mm to 5.6 mm. Both the FE simulation and OCE results confirm that the group velocity of the elastic wave decreases with radius of curvature but increases with thickness. These results demonstrate that the effects of the curvature and thickness must be considered in the further development of accurate wave models for reconstructing biomechanical properties of the cornea. PMID- 26130827 TI - An ethicist's commentary on shelter reluctant to adopt. PMID- 26130826 TI - The CVMA and the veterinary profession in Canada. PMID- 26130828 TI - 2014 Annual Report of the Canadian Veterinary Medical Association. PMID- 26130829 TI - The increasing risk of Lyme disease in Canada. AB - There is an increasing risk of Lyme disease in Canada due to range expansion of the tick vector, Ixodes scapularis. The objectives of this article are to i) raise public awareness with the help of veterinarians on the emerging and expanding risk of Lyme disease across Canada, ii) review the key clinical features of Lyme disease in dogs, and iii) provide recommendations for veterinarians on the management of Lyme disease in dogs. PMID- 26130830 TI - Modest cost of veterinary services and goods to farmers in Canada. PMID- 26130831 TI - Demographics of the Canadian dairy industry from 1991 to 2011. AB - A retrospective study of the demographics of the Canadian dairy industry was conducted using data derived from Statistics Canada's Census of Agriculture from 1991 to 2011. This longitudinal study shows that Canada's dairy industry has undergone considerable consolidation. From 1991 to 2011, the number of dairy producers and dairy farms decreased by 48.9% and 61.9%, respectively. Furthermore, this trend in consolidation is likely to continue; nearly half (45.8%) of all dairy producers in Canada were >= 50 y of age in 2011. Not only will most of these producers be retired by 2021, but younger producers will also exit the industry for other reasons. These findings mirror what is occurring in Canada's cow-calf industry, underscoring that supply-managed sectors experience demographic consolidation similar to non-supply managed sectors. These substantial changes will have ramifications for the veterinary profession. There will be fewer but larger farms, and the services and knowledge demanded of veterinarians will change accordingly, which has implications for food animal veterinary education. PMID- 26130832 TI - Autologous vaccination for the treatment of equine sarcoids: 18 cases (2009 2014). AB - The purpose of this retrospective case series was to assess the outcome of an autologous vaccination procedure on single and multiple sarcoid lesions, determine complication rate, and report owner satisfaction. Medical records (18 cases) from January 2009 through May 2014 were evaluated to identify horses undergoing the procedure. Signalment, number, size, anatomic location of lesions, and type of historical treatment were recorded. Follow-up was obtained via standardized owner survey, veterinary examination, and digital images. Data recorded and analyzed included ancillary therapies post-procedure, decrease in number and/or size of sarcoid lesions, sarcoid regrowth, complications, and owner satisfaction. There was a decrease in number of lesions observed by owners in 75% of cases and a decrease in size of sarcoids in 93.8% of cases. Clinical regression observed by owners was noted in 68.8% of cases. There were complications in 43.8% of cases and owner satisfaction in 75% of cases. PMID- 26130833 TI - Long-term prospective evaluation of intestinal anastomosis using stainless steel staples in 14 dogs. AB - This prospective clinical study evaluated the use, complications, and clinical and ultrasonographic follow-ups of end-to-end intestinal anastomoses with skin staples in naturally occurring diseases in canine small and large intestines. Intestinal anastomoses were performed in 14 dogs and pre-, peri-, and postoperative data were recorded. Postoperative clinical and ultrasound evaluations were performed at regular intervals for 1 year. The mean time taken to construct the anastomosis was 5 min. There were no intraoperative complications. Hemorrhage and colonic stricture were the main postoperative complications. Staple loss occurred in 2 cases. Absence of wall layering and focal wall thickening were observed in all cases at each ultrasonographic follow up. Hyperechoic fat was observed in all but 1 of the cases at month 1. Nine dogs were alive with normal digestive function at the end of the study. The skin stapler technique enabled rapid construction of consistent anastomoses with inexpensive stapling material. PMID- 26130834 TI - Antimicrobial dispensing by Ontario dairy veterinarians. AB - This questionnaire-based cross-sectional study was designed to capture the demographics of dairy practitioners in Ontario and to describe aspects of antimicrobial dispensing on-farm and over-the-counter by these veterinarians. The information collected revealed that the prescription status of a drug and the level of veterinary-client-patient relationship were important elements of dispensing policies. Over-the-counter dispensing records were incomplete, while only a small proportion of on-farm dispensing records contained pertinent information and directions as required by the Veterinarians Act. While respondents recognized that antimicrobial use in dairy herds could lead to resistance in cattle, few indicated that this was a significant public health issue. Veterinarians can play a key role in antimicrobial stewardship, part of which is the provision of complete written dispensing instructions to producers for antimicrobial use in dairy cattle. PMID- 26130835 TI - Pharmacokinetics and bioequivalence of 2 meloxicam oral dosage formulations in healthy adult horses. AB - Meloxicam, a non-steroidal anti-inflammatory drug, is approved for use in horses in several countries, but an equine formulation is not available in North America. However, meloxicam is being used in an extra-label manner in horses in Canada. The purpose of this study, therefore, was to assess the bioequivalence of an approved oral meloxicam suspension (Metacam 15 mg/mL for horses; Boehringer Ingelheim Vetmedica GmBH, Ingelheim, Germany) from the European Union with human meloxicam tablets (Meloxicam 15 mg tablets; TEVA Canada, Toronto, Ontario) compounded with molasses to improve palatability and administration. The geometric mean ratios (GMR test/reference) and the 90% confidence intervals of the pivotal pharmacokinetic parameters (area under the curve and maximum concentration) were within the defined limits of 80% to 125% generally accepted for products to be considered bioequivalent. Therefore, use of human meloxicam tablets compounded with molasses would be expected to produce a similar clinical response in horses as the approved oral product from the European Union. PMID- 26130836 TI - Transient diabetes mellitus in a domestic ferret (Mustela putorius furo). AB - A 3.5-year-old spayed female ferret, fed a diet high in refined sugar, was referred for lethargy, polyuria, polydipsia, and polyphagia. Diabetic ketoacidosis was diagnosed. Treatment included insulin therapy and a low carbohydrate diet. Diabetes mellitus resolved 54 d later, and insulin therapy was discontinued. There has been no recurrence of the diabetes mellitus. PMID- 26130837 TI - Hypertrophic osteopathy associated with hepatocellular carcinoma in a dog. AB - A 9-year-old spayed female dog diagnosed with hepatocellular carcinoma and hypertrophic osteopathy was negative for additional lesions on computed tomography of the thorax and abdomen. Resection of the affected liver lobe resulted in resolution of clinical signs. This is the first case of hypertrophic osteopathy secondary to hepatocellular carcinoma. PMID- 26130838 TI - Diode laser coagulation for the treatment of epistaxis in a Scottish fold cat. AB - We report the case of a 4-year-old, castrated 4.2-kg Scottish fold cat with recurrent epistaxis that was unresponsive to medical therapy. Diathermocoagulation of the nasal mucosa with a diode laser controlled the epistaxis and there was no significant recurrence of epistaxis during 1 year of follow-up. PMID- 26130839 TI - Glenoid dysplasia and osteochondritis dissecans in a cat. AB - A 2-year-old Maine Coon cat was presented for a right forelimb lameness. Computed tomography of the shoulder revealed a shallow glenoid, osteophyte deposition at the caudal humeral head and medial glenoid, and an intra-articular osseous body. This cat had glenoid dysplasia and osteochondritis dissecans of the glenoid. PMID- 26130840 TI - Successful resolution of a preputial prolapse in an alpaca using medical therapy. AB - A 2-year-old intact male alpaca was presented for a post-breeding preputial prolapse of 5 days duration. The internal lamina of the prepuce was prolapsed approximately 6 cm and the exposed preputial epithelium was edematous and necrotic. Following 7 days of medical treatment, resolution of the preputial prolapse was achieved. PMID- 26130841 TI - Clinical characteristics of horses and foals diagnosed with cleft palate in a referral population: 28 cases (1988-2011). AB - The objective of this case series was to characterize the population, case presentations, and outcomes of 28 equids diagnosed with cleft palate over a 25 year period. The incidence of cleft palate was 0.04%. The median age at presentation was 2 mo (range: 1 d to 3 y). Fifty percent of the animals were < 2 mo old, 21% were >= 2 mo but < 1 y old, and 29% were 1 y of age or older. Males and females were nearly equally represented. Short-term outcomes included euthanasia in 50%, surgical repair in 11%, supportive care in 4%, and no treatment in 32% of cases; 46% of the animals survived to discharge. Defects involving both the hard and soft palate and/or aspiration pneumonia generally had less favorable outcomes. Though cleft palate is rare in horses, it should be considered as a differential diagnosis in horses of all ages with nasal discharge, a cough, a history of recurrent respiratory infections, poor growth, or chronic submandibular lymphadenopathy. Endoscopic evaluation of the pharynx may aid in earlier diagnosis and prognostication for owners. PMID- 26130842 TI - Anaplasmosis in a dog on Vancouver Island. PMID- 26130843 TI - A strong year in client numbers for much of Canada. PMID- 26130844 TI - Diagnostic ophthalmology. Microphthalmos and multiple ocular anomalies (MOA) OU consistent with merle ocular dysgenesis (MOD). PMID- 26130845 TI - An extremely wideband and lightweight metamaterial absorber. AB - This paper presents a three-dimensional microwave metamaterial absorber based on the stand-up resistive film patch array. The absorber has wideband absorption, lightweight, and polarization-independent properties. Our design comes from the array of unidirectional stand-up resistive film patches backed by a metallic plane, which can excite multiple standing wave modes. By rolling the resistive film patches as a square enclosure, we obtain the polarization-independent property. Due to the multiple standing wave modes, the most incident energy is dissipated by the resistive film patches, and thus, the ultra-wideband absorption can be achieved by overlapping all the absorption modes at different frequencies. Both the simulated and experimental results show that the absorber possesses a fractional bandwidth of 148.2% with the absorption above 90% in the frequency range from 3.9 to 26.2 GHz. Moreover, the proposed absorber is extremely lightweight. The areal density of the fabricated sample is about 0.062 g/cm2, which is approximately equivalent to that of eight stacked standard A4 office papers. It is expected that our proposed absorber may find potential applications such as electromagnetic interference and stealth technologies. PMID- 26130846 TI - Comparisons of characteristic timescales and approximate models for Brownian magnetic nanoparticle rotations. AB - Magnetic nanoparticles are promising tools for a host of therapeutic and diagnostic medical applications. The dynamics of rotating magnetic nanoparticles in applied magnetic fields depend strongly on the type and strength of the field applied. There are two possible rotation mechanisms and the decision for the dominant mechanism is often made by comparing the equilibrium relaxation times. This is a problem when particles are driven with high-amplitude fields because they are not necessarily at equilibrium at all. Instead, it is more appropriate to consider the "characteristic timescales" that arise in various applied fields. Approximate forms for the characteristic time of Brownian particle rotations do exist and we show agreement between several analytical and phenomenological-fit models to simulated data from a stochastic Langevin equation approach. We also compare several approximate models with solutions of the Fokker-Planck equation to determine their range of validity for general fields and relaxation times. The effective field model is an excellent approximation, while the linear response solution is only useful for very low fields and frequencies for realistic Brownian particle rotations. PMID- 26130847 TI - Comparison of culture versus quantitative real-time polymerase chain reaction for the detection of Taylorella equigenitalis in field samples from naturally infected horses in Canada and Germany. AB - A quantitative real-time polymerase chain reaction method (qPCR) was developed and tested for the detection of Taylorella equigenitalis. It was shown to have an analytical sensitivity of 5 colony-forming units (CFU) of T. equigenitalis when applied to the testing of culture swabs that mimicked field samples, and a high analytical specificity in not reacting to 8 other commensal bacterial species associated with horses. As designed, it could also differentiate specifically between T. equigenitalis and T. asinigenitalis. The qPCR was compared to standard culture in a study that included 45 swab samples from 6 horses (1 stallion, 5 mares) naturally infected with T. equigenitalis in Canada, 39 swab samples from 5 naturally infected stallions in Germany, and 311 swab samples from 87 culture negative horses in Canada. When the comparison was conducted on an individual sample swab basis, the qPCR had a statistical sensitivity and specificity of 100% and 96.4%, respectively, and 100% and 99.1% when the comparison was conducted on a sample set basis. A comparison was also made on 203 sample swabs from the 5 German stallions taken over a span of 4 to 9 mo following antibiotic treatment. The qPCR was found to be highly sensitive and at least as good as culture in detecting the presence of T. equigenitalis in post-treatment samples. The work demonstrates that the qPCR assay described here can potentially be used to detect the presence of T. equigenitalis directly from submitted sample swabs taken from infected horses and also for determining T. equigenitalis freedom following treatment. PMID- 26130848 TI - Probe-free real-time reverse transcription polymerase chain reaction assays for the detection and typing of porcine reproductive and respiratory syndrome virus in Canada. AB - Porcine reproductive and respiratory syndrome (PRRS) has tremendous impact on the pork industry in North America. The molecular diagnosis of infection with PRRS virus (PRRSV) is hampered by its considerable strain diversity. In this study, 43 previously published or newly developed primers for probe-free real-time reverse transcription polymerase chain reaction (RT-PCR) were evaluated on their sensitivity, specificity, reproducibility, and repeatability, using a diverse panel of 36 PRRSV strains as well as other arteriviruses and unrelated porcine viruses. Three primer pairs had excellent diagnostic and analytical sensitivity on par with a probe-based reference assay, absolute specificity to virus genotype and species, as well as over 95% reproducibility and repeatability across a wide dynamic range. PMID- 26130849 TI - Applying a kinetic method to an indirect ELISA measuring Ostertagia ostertagi antibodies in milk. AB - Indirect enzyme-linked immunosorbent assays (ELISAs) are frequently run as endpoint ELISAs (e-ELISAs). However, kinetic ELISAs (k-ELISAs) have certain advantages over e-ELISAs. The objective of this study was to understand the relationship between e-ELISA and k-ELISA results. Specifically, to determine whether it was possible to run both k-ELISA and e-ELISA on the same plate and establish an appropriate time interval for k-ELISA measurements. A normalization method for k-ELISA slopes (slope ratio) is proposed. Using an indirect e-ELISA test measuring antibodies against Ostertagia ostertagi in milk from dairy cattle, we found that running a k-ELISA had no effect on optical density ratio results of an e-ELISA on the same plate, and that agreement was very strong at 10, 15, and 28 min, allowing for a reduction in the total processing time for ELISA tests. PMID- 26130850 TI - A comparative proteomic study of plasma in feline pancreatitis and pancreatic carcinoma using 2-dimensional gel electrophoresis to identify diagnostic biomarkers: A pilot study. AB - While pancreatitis is now recognized as a common ailment in cats, the diagnosis remains challenging due to discordant results and suboptimal sensitivity of ultrasound and specific feline pancreatic lipase (Spec fPL) assay. Pancreatitis also shares similar clinical features with pancreatic carcinoma, a rare but aggressive disease with a grave prognosis. The objective of this pilot study was to compare the plasma proteomes of normal healthy cats (n = 6), cats with pancreatitis (n = 6), and cats with pancreatic carcinoma (n = 6) in order to identify potential new biomarkers of feline pancreatic disease. After plasma protein separation by 2-dimensional gel electrophoresis, protein spots were detected by Coomassie Brilliant Blue G-250 staining and identified by mass spectrometry. Alpha-1-acid glycoprotein (AGP), apolipoprotein-A1 (Apo-A1), and apolipoprotein-A1 precursor (Pre Apo-A1) appeared to be differentially expressed, which suggests the presence of a systemic acute-phase response and alteration of lipid metabolism in cats with pancreatic disease. Future studies involving greater case numbers are needed in order to assess the utility of these proteins as potential biomarkers. More sensitive proteomic techniques may also be helpful in detecting significant but low-abundance proteins. PMID- 26130851 TI - Single nucleotide polymorphisms in the bovine Histophilus somni genome; a comparison of new and old isolates. AB - Histophilus somni, a causative agent of the bovine respiratory disease complex, can also cause a variety of systemic disorders, including bronchopneumonia, myocarditis, pericarditis, arthritis, pleuritis, and infectious thrombotic meningoencephalitis. The purpose of this study was to determine if currently circulating strains differ from those of the 1980s by identifying genomic changes. Single nucleotide polymorphisms (SNPs) and insertion and deletion (INDEL) sites were examined by whole-genome sequencing in 12 samples, 6 old and 6 new. The 31 028 SNP/INDELs recorded were compared against the reference genome sequence of the pathogenic H. somni strain 2336. The distribution of about 75% of these SNPs within a specified gene differed between old and new isolates and did not follow any particular pattern. The other 25% clustered into 2 groups containing the same SNPs in various genes: group I included 5 old isolates and 1 new isolate; group II included 5 new isolates and 1 old isolate. For putative virulence genes there were more SNPs in group I compared with strain 2336, itself an older isolate, than in group II. Although only 25% of all the SNPs formed 2 clusters, the results suggest some genetic difference in various genes between old and new strains. PMID- 26130852 TI - Expression of O(6)-methylguanine-DNA methyltransferase causes lomustine resistance in canine lymphoma cells. AB - The DNA repair protein O (6)-methylguanine-DNA methyltransferase (MGMT) causes resistance to nitrosoureas in various human cancers. In this study, we analyzed the correlation between canine lymphomas and MGMT in vitro. Two of five canine lymphoma cell lines required higher concentrations of lomustine to inhibit cell growth by 50%, but their sensitivity to the drug increased when they were cultured with an MGMT inhibitor. Fluorometric oligonucleotide assay and real-time polymerase chain reaction of these cell lines revealed MGMT activity and high MGMT mRNA expression, respectively. We analyzed the methylation status of the CpG islands of the canine MGMT gene by the bisulfite-sequencing method. Unlike human cells, the canine lymphoma cell lines did not show significant correlation between methylation status and MGMT suppression levels. Our results suggest that in canine lymphoma MGMT activity may influence sensitivity to nitrosoureas; thus, inhibition of MGMT activity would benefit nitrosourea-resistant patients. Additional studies are necessary to elucidate the mechanism of regulation of MGMT expression. PMID- 26130853 TI - Effect of additional human chorionic gonadotrophin (hCG) on follicular growth and ovulation in gonadotrophin-treated gilts. AB - The objective of this study was to determine the effect of additional human chorionic gonadotrophin (hCG) on the ovarian response of gilts previously treated with 200 IU hCG combined with 400 IU equine chorionic gonadotrophin (eCG) (eCG/hCG). Seventy-one prepuberal gilts (105 +/- 7.5 kg) were assigned to groups: i) eCG/hCG (hCG-0; n = 25); ii) eCG/hCG followed by 100 IU of hCG at 24 h (hCG 100; n = 24); iii) eCG/hCG followed by 200 IU hCG at 24 h (hCG-200; n = 10); and iv) controls (CON; n = 12). Ovulation response was assessed by ovarian dissection or real-time ultrasonography. Additional hCG did not significantly improve numbers of gilts ovulating. Numbers of corpora lutea increased with hCG, and was higher in hCG-200 (P < 0.01). Compared to hCG-0, the frequency of cysts in gilts was higher in hCG-100 (P < 0.05) and further increased in hCG-200 (P < 0.01). The number of cysts per gilt was dose-dependently increased by additional hCG. We conclude that supplemental hCG will increase the number of corpora lutea but will be associated with follicular cyst development in a dose dependent manner. PMID- 26130854 TI - Potentiation of epidural lidocaine by co-administering tramadol by either intramuscular or epidural route in cats. AB - This study investigated the analgesic and systemic effects of intramuscular (IM) versus epidural (EP) administration of tramadol as an adjunct to EP injection of lidocaine in cats. Six healthy, domestic, shorthair female cats underwent general anesthesia. A prospective, randomized, crossover trial was then conducted with each cat receiving the following 3 treatments: EP injection of 2% lidocaine [LEP; 3.0 mg/kg body weight (BW)]; EP injection of a combination of lidocaine and 5% tramadol (LTEP; 3.0 and 2.0 mg/kg BW, respectively); or EP injection of lidocaine and IM injection of tramadol (LEPTIM; 3.0 and 2.0 mg/kg BW, respectively). Systemic effects, spread and duration of analgesia, behavior, and motor blockade were determined before treatment and at predetermined intervals afterwards. The duration of analgesia was 120 +/- 31 min for LTEP, 71 +/- 17 min for LEPTIM, and 53 +/- 6 min for LEP (P < 0.05; mean +/- SD). The cranial spread of analgesia obtained with LTEP was similar to that with LEP or LEPTIM, extending to dermatomic region T13-L1. Complete motor blockade was similar for the 3 treatments. It was concluded that tramadol produces similar side effects in cats after either EP or IM administration. Our findings indicate that EP and IM tramadol (2 mg/kg BW) with EP lidocaine produce satisfactory analgesia in cats. As an adjunct to lidocaine, EP tramadol provides a longer duration of analgesia than IM administration. The adverse effects produced by EP and IM administration of tramadol were not different. Further studies are needed to determine whether EP administration of tramadol could play a role in managing postoperative pain in cats when co-administered with lidocaine after painful surgical procedures. PMID- 26130855 TI - Emergence of highly virulent pseudorabies virus in southern China. AB - Pseudorabies has been controlled efficiently in China for many years by vaccination. However, it suddenly broke out in many pig farms in 2012-2013 in southern China. In this study, a systematic investigation that included virus isolation, genetic and pathological studies, and immunogenicity analysis was carried out with the aim of understanding the pathogenetic and antigenic features of novel isolates of pseudorabies virus (PRV). Of 38 tissue samples collected from pigs with clinical signs of pseudorabies on 13 farms in 4 provinces in southern China in 2012-2013, 29 showed wild-type PRV infection by polymerase chain reaction. Sequence analysis of 5 isolates from the 4 provinces showed that they belonged to a relatively independent cluster that shared 2 insertions of a single amino acid in the gE gene and 1 insertion of 7 amino acids in the gC gene. In experiments, isolate ZJ01 caused death in 100% of pigs that were either 14 or 80 days old. The serum antibodies to the commercial PRV vaccines had significantly lower neutralizing activity against the ZJ01 isolate than against the vaccine strains. The antigenic relatedness between ZJ01 and the vaccine strains was 0.378 to 0.455. These findings indicated that a novel, highly virulent PRV strain with antigenic variance had spread widely in southern China. PMID- 26130856 TI - Immune responses to oral vaccination with Salmonella-delivered avian pathogenic Escherichia coli antigens and protective efficacy against colibacillosis. AB - In this study, the immune responses to and protective efficacy of a live attenuated Salmonella-delivered vaccine candidate secreting the papA, papG, iutA, and clpG antigens of Escherichia coli were evaluated against infection with avian pathogenic E. coli (APEC) in layer chickens. Primary vaccination was done at age 7 d and booster vaccination at age 5 wk. The levels of intestinal secretory immunoglobulin A specific to the 4 antigens were significantly higher in the vaccinated group than in the control group. A potent lymphocyte-proliferation response and increased levels of interferon-gamma, interleukin-2, and interleukin 6 in the plasma and in culture supernatants of antigen-stimulated lymphocytes from the vaccinated group suggested significant induction of the cell-mediated immune response in this group compared with the control group. Upon challenge with a virulent APEC strain at 8 wk of age, the vaccinated group had no deaths, whereas the control group had a 15% mortality rate. In addition, the morbidity rate was significantly higher in the control group (55%) than in the vaccinated group (15%). Thus, giving primary and booster vaccination with the Salmonella delivered APEC vaccine candidate significantly elevated both mucosal and cellular immune responses, which protected the chickens against colibacillosis. PMID- 26130857 TI - Comparison of a live attenuated Salmonella Enteritidis vaccine candidate secreting Escherichia coli heat-labile enterotoxin B subunit with a commercial vaccine for efficacy of protection against internal egg contamination by Salmonella in hens. AB - This study compared a new live attenuated Salmonella Enteritidis vaccine candidate secreting Escherichia coli heat-labile enterotoxin B subunit (SE-LTB) with a commercial Salmonella Enteritidis (SE) vaccine for efficacy of protection against SE infection in laying hens. Chickens were divided into 3 groups of 20 each. Group A chickens were inoculated orally with phosphate-buffered saline and served as controls, group B chickens were inoculated orally with the vaccine candidate, and group C chickens were inoculated intramuscularly with a commercial vaccine, the primary inoculation in groups B and C being at 10 wk of age and the booster at 16 wk. Groups B and C showed significantly higher titers of plasma immunoglobulin G, intestinal secretory immunoglobulin A, and egg yolk immunoglobulin Y antibodies compared with the control group, and both vaccinated groups showed a significantly elevated cellular immune response. After virulent challenge, group B had significantly lower production of thin-shelled and/or malformed eggs and a significantly lower rate of SE contamination of eggs compared with the control group. Furthermore, the challenge strain was detected significantly less in all of the examined organs of group B compared with the control group. Group C had lower gross lesion scores only in the spleen and had lower bacterial counts only in the spleen, ceca, and ovary. These findings indicate that vaccination with the SE-LTB vaccine candidate can efficiently reduce internal egg and internal organ contamination by Salmonella and has advantages over the commercial vaccine. PMID- 26130858 TI - Pharmacological effects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis. AB - Multicomponent nutraceuticals are becoming increasingly popular treatments or adjunctive therapies for osteoarthritis in veterinary medicine despite lack of evidence of efficacy for many products. The objective of this study was to evaluate the anti-inflammatory and antioxidant activities of a commercially available C-phycocyanin-based nutraceutical and select constituent ingredients in an in-vitro model of canine osteoarthritis. Normal canine articular chondrocytes were used in an in-vitro model of osteoarthritis. Inflammatory conditions were induced using interleukin-1beta. The nutraceutical preparation as a whole, its individual constituents, as well as carprofen were evaluated at concentrations of 0 to 250 MUg/mL for reduction of the following inflammatory mediators and indicators of catabolism of the extracellular matrix: prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TFN-alpha), interleukin-6 (IL-6), metalloproteinase 3 (MMP-3), nitric oxide, and sulfated glycosaminoglycans (sGAGs). Validated, commercially available assay kits were used for quantitation of inflammatory mediators. The antioxidant capacities, as well as cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and lipoxygenase (LOX) inhibitory activities of the whole nutraceutical preparation and select constituents, were also assessed using validated commercially available assay kits. The antioxidant capacity of the nutraceutical and constituents was concentration-dependent. The nutraceutical and constituents appear to display anti-inflammatory activity primarily through the inhibition of COX-2. The nutraceutical displayed similar strength to carprofen in reducing TNF-alpha, IL-6, MMP-3, nitric oxide, and sGAGs at select concentration ranges. The C-phycocyanin (CPC)-based nutraceutical and constituents may be able to mediate 3 primary pathogenic mechanisms of osteoarthritis: inflammation, chondral degeneration, and oxidative stress in vitro. The nutraceutical may be clinically useful in veterinary medicine and its efficacy should be further investigated in vivo. PMID- 26130859 TI - Histopathological findings in farmed rainbow trout (Oncorhynchus mykiss) naturally infected with 3 different Aeromonas species. AB - This study describes the macroscopic and microscopic lesions in farmed rainbow trout (Oncorhynchus mykiss) naturally infected with genetically identified Aeromonas salmonicida, A. hydrophila, and A. veronii species. The genus Aeromonas includes bacteria that naturally inhabit both waterways and organisms. At least 27 Aeromonas species have been identified to date, some of which can cause significant economic losses in aquaculture. As up to 68.8% of Aeromonas isolates may be misidentified in routine biochemical and phenotypic tests, however, reported cases of Aeromonas infection in fish may be wrongly identified. Our findings confirmed that the 3 Aeromonas species studied are associated with septicemia and dermal lesions in rainbow trout. PMID- 26130861 TI - Comments on Unger J: What Qualities Define an Expert Family Doctor? The Patients Have Our Backs. Clinical Diabetes 31:145-147, 2013. DOI:10.2337/diaclin.31.4.145. PMID- 26130860 TI - Different types of stainless steel used in equipment in meat plants do not affect the initial microbial transfer, including pathogens, from pork skin. AB - This study describes and measures the impact of different compositions and finishes of stainless steel used in equipment in the meat industry on the transfer of natural flora and selected pathogens from artificially contaminated pork skin. It is known that the adhesion to surfaces of Listeria monocytogenes and Salmonella, 2 pathogens frequently found in contaminated pork meat, depends on the nature and roughness of the surface. Our results show no statistically significant differences in microbial transfer regardless of the types of stainless steel considered, with the highest measured transfer difference being 0.18 log colony-forming units (CFUs)/800 cm(2). Moreover, no differences in total microbial community were observed after transfer on the 5 types of stainless steel using single-strand conformation polymorphism (SSCP). It was concluded that the different characteristics of the stainless steel tested did not affect the initial bacterial transfer in this study. PMID- 26130864 TI - Clinical Considerations for Insulin Pharmacotherapy in Ambulatory Care, Part One: Introduction and Review of Current Products and Guidelines. AB - In Brief This article describes available insulin products and published guidelines to aid clinicians in making treatment decisions for insulin-dependent patients with type 2 diabetes. It establishes the need for a thorough evaluation of the literature regarding ambulatory insulin dosing to further inform providers who manage insulin therapy for patients with type 2 diabetes. PMID- 26130863 TI - Obesity and Testosterone Levels in Ghanaian Men With Type 2 Diabetes. AB - Testosterone plays a vital role in obesity, glucose homeostasis, and lipid metabolism. The aim of this study was to investigate androgen levels and its association with obesity in Ghanaian men with type 2 diabetes. The study showed that serum total and free testosterone concentrations were lower in male patients with type 2 diabetes and that obesity was strongly associated with low levels of total and free testosterone in Ghanaian men with type 2 diabetes. PMID- 26130865 TI - Dizziness and Loss of Balance in Individuals With Diabetes: Relative Contribution of Vestibular Versus Somatosensory Dysfunction. AB - The authors studied patients with diabetes and complaints of dizziness to determine whether peripheral neuropathy or inner ear dysfunction was more likely to disturb balance. Quantitative testing showed that the majority failed to maintain balance in vestibular-related conditions and had normal equilibrium scores in conditions relying on somatosensory input. Vestibular dysfunction should be an immediate consideration in patients with diabetes and complaints of dizziness regardless of the presence of peripheral neuropathy. PMID- 26130866 TI - U.S. Air Force Telehealth Initiative to Assist Primary Care Providers in the Management of Diabetes. PMID- 26130867 TI - Efficacy and Safety of Canagliflozin as Add-On Therapy to Metformin in Type 2 Diabetes. PMID- 26130868 TI - End of the Road: Diabetes Care When Insulin May Not Be an Option. PMID- 26130869 TI - Speaking to Patients About Diabetes Risk: Is Terminology Important? PMID- 26130870 TI - West Nile virus and the 2012 outbreak: The Baylor University Medical Center experience. AB - West Nile virus (WNV) has been responsible for multiple outbreaks and has shown evolution in its clinical manifestation. The Centers for Disease Control and Prevention has provided diagnostic criteria in classifying the variety of WNV infection; however, application of these criteria can prove challenging during outbreaks, and understanding the array of presentations and patient population is clinically important. In this article, we present the challenges encountered during the 2012 outbreak at one institution. PMID- 26130871 TI - Comparison of long-term follow up of laparoscopic versus open colectomy for transverse colon cancer. AB - Clinical Outcomes of Surgical Therapy (COST) was a landmark study demonstrating that laparoscopic-assisted colectomy had oncologic outcomes similar to those of open colectomy for colon cancer, but transverse colon cancers (TCCs) were excluded from that study. Oncologic results of a laparoscopic resection for TCC are unknown. This single-institution retrospective 3:1 case-matched review examined patients treated for TCC from January 1, 1996, to April 15, 2009. Laparoscopic colectomy (LC) and open colectomy (OC; extended right, extended left, and total abdominal) cases completed for Stage I to III adenocarcinoma of the transverse colon (hepatic flexure, transverse colon, and splenic flexure) were analyzed. Patients were matched for age, tumor location, and stage. Primary endpoints were overall survival and disease-free survival. Secondary endpoints were length of stay and pathologic parameters. One hundred and twenty-three OC cases were matched with 41 LC cases. There were four conversions (9.7%) in the LC group. Length of stay was reduced by 28% in the LC group (P = 0.02). Complication rate and severity were similar between the two groups (29% vs 24%; P = 0.68). Lymph node harvest was higher in the LC group than in the OC group (23.3 vs 18.6; P = 0.03). All pathologic margins were clear, and no local recurrence was found in either group. Five-year overall survival (61% vs 59%; P = 0.39) and disease free survival (88% vs 82%; P = 0.23) were similar in the two groups. Short-term recovery was faster and lymph node harvest was improved in the LC group. Thus, laparoscopic management of TCC is a safe and feasible procedure. PMID- 26130872 TI - Mortality by treatment in patients >=80 years of age with gastroesophageal cancer seen in a 20-year period at a single medical center. AB - The treatment approach to patients 80 years of age and older with gastroesophageal cancer at Baylor Scott and White in Temple, Texas, has historically favored conservative measures in the form of palliation and observation. To evaluate this trend in practice, the administered treatments and subsequent patient outcomes of this group were retrospectively reviewed. The study group included all patients 80 years of age and older with a diagnosis of gastroesophageal cancer seen at our facility between 1991 and 2010. Of the 117 cases, 49% received none of the available treatment modalities. The median overall survival (OS) of patients who received treatment, however, was significantly longer than the OS of those who did not, regardless of modality. Specifically, surgical intervention offered an almost double median OS compared with no therapy (6.8 vs. 3.9 months, respectively; P = 0.02); chemotherapy, an almost 4-fold OS benefit (14.8 vs. 3.9 months; P = 0.03); and radiation therapy, a >3-fold OS benefit (11.1 vs. 3.5 months; P = 0.04). These results further substantiate chronological age as an inaccurate predictor of treatment benefit, and age alone should not dictate the administration or withholding of available treatment options. PMID- 26130873 TI - Trends in the neonatal mortality rate in the last decade with respect to demographic factors and health care resources. AB - To understand factors contributing to the neonatal mortality rate (NMR), we studied trends in the NMR during 2000 to 2009 with respect to demographic factors and health care resources. Birth- and death-linked mortality data for 14,168 neonatal deaths that occurred between 2000 and 2009 were obtained from the Texas Department of Health and Human Services. Demographic factors and health care resource data were analyzed using analysis of variance, chi-square tests, and linear regression analysis. The average NMR increased from 3.37 in 2000 to 3.77 in 2009. The NMR in blacks ranged from 6.57 to 8.97 during the study period. Among the babies who died, the mean birthweight decreased from 1505 to 1275 g (P < 0.001) and the mean gestational age decreased from 28.4 to 27.8 weeks (P < 0.001). Cesarean section deliveries increased from 32.7% to 44.9% (P < 0.001). The percentage of mothers receiving prenatal care increased from 81.4% to 86.6% (P < 0.001). Mothers with a college education increased from 8.8% to 20.5% (P < 0.001). The median household income increased from $41,047 to $49,189 (P < 0.001). The number of neonatal intensive care unit beds increased from 33.4 to 56 per 10,000 births, and the number of neonatologists increased from 0.27 to 0.40 per 10,000 women of 15 to 44 years of age. In conclusion, the NMR didn't improve despite improvements in demographic factors and health care resources. Racial disparities persist, with a high NMR in the black population. We speculate a possible genetic predisposition related to ethnicity, and a potentially higher rate of extreme prematurity might have contributed to a high NMR in the study population. PMID- 26130874 TI - Effect of adding tetracaine to bupivacaine on duration of analgesia in supraclavicular brachial plexus nerve blocks for ambulatory shoulder surgery. AB - The objective of this study was to determine if the addition of 1% tetracaine to 0.25% bupivacaine prolonged the duration of postoperative analgesia of supraclavicular brachial plexus nerve blockade for patients undergoing ambulatory shoulder surgery. We conducted a prospective, double-blinded, randomized controlled clinical study at an ambulatory surgery center utilizing ultrasound- and nerve stimulation-guided supraclavicular nerve blockade for postoperative analgesia. The control group received 30 mL of 0.25% bupivacaine plus 4 mL preservative-free saline. The study group received 30 mL of 0.25% bupivacaine plus 4 mL of 1% tetracaine. Patients documented their visual analog scale scores and intake of pain medications for 3 days. Primary outcomes included time of first postoperative pain, time of first postoperative pain pill, and time of return of motor and sensory function. Secondary outcomes included pain score and pain medication intake trends and adverse events secondary to the nerve block. A total of 84 patients completed the study, 42 patients in each group. The study group was statistically significantly older than the control group (mean age, 54 vs 48 years; P = 0.04). The mean duration of analgesia was 16.6 +/- 8.3 h for the control group and 17.1 +/- 7.3 h for the study group (P = 0.69). No outcomes were statistically different. In conclusion, there was no significant difference in duration of postoperative analgesia with the addition of 1% tetracaine to 0.25% bupivacaine in supraclavicular brachial plexus nerve blockade. No differences were identified in postoperative pain medications, pain scores, or complications. PMID- 26130875 TI - Comparison of documentation and evidence-based medicine use for non-ST-segment elevation myocardial infarction among cardiology, teaching, and nonteaching teams. AB - Non-ST-segment elevation myocardial infarctions (NSTEMI) are common and cause significant morbidity and mortality. Following evidence-based medicine (EBM) guidelines is one way to ensure that these patients are cared for appropriately. This pilot study examined data from patients with NSTEMI to assess both documentation quality and use of EBM across multiple teams. Medical records were reviewed for significant differences in documentation quality in areas including history and physical exam, treatment, and inpatient mortality. While total documentation quality and mortality were not significantly different between groups, cardiology teams adhered to evidence-based recommendations more often than other teams. PMID- 26130876 TI - Assessment of leadership training needs of internal medicine residents at the Massachusetts General Hospital. AB - Internal medicine (IM) physicians, including residents, assume both formal and informal leadership roles that significantly impact clinical and organizational outcomes. However, most internists lack formal leadership training. In 2013 and 2014, we surveyed all rising second-year IM residents at a large northeastern academic medical center about their need for, and preferences regarding, leadership training. Fifty-five of 113 residents (49%) completed the survey. Forty-four residents (80% of respondents) reported a need for additional formal leadership training. A self-reported need for leadership training was not associated with respondents' gender or previous leadership training and experience. Commonly cited leadership skill needs included "leading a team" (98% of residents), "confronting problem employees" (93%), "coaching and developing others" (93%), and "resolving interpersonal conflict" (84%). Respondents preferred to learn about leadership using multiple teaching modalities. Fifty residents (91%) preferred to have a physician teach them about leadership, while 19 (35%) wanted instruction from a hospital manager. IM residents may not receive adequate leadership development education during pregraduate and postgraduate training. IM residents may be more likely to benefit from leadership training interventions that are physician-led, multimodal, and occur during the second year of residency. These findings can help inform the design of effective leadership development programs for physician trainees. PMID- 26130877 TI - Abstracts from the First Annual Scholarly Day. AB - The Department of Medical Education at Baylor University Medical Center at Dallas hosted its first annual Scholarly Day to showcase the research efforts of medical students, residents, and fellows. Hania Wehbe-Janek, PhD, vice president for academic research integration for Baylor Scott and White Health Central Texas, shared the plenary session, "Building a Culture of Research at Academic Medical Centers: Impact on Medical Education and Recommended Practices." Stuart Black, MD, John Fordtran, MD, Ronald C. Jones, MD, Michael A. Ramsay, MD, William C. Roberts, MD, and Hania Wehbe-Janek, PhD, served as judges of the posters and the oral presentations. Winners in each category were as follows: best fellow poster, "Diet pattern and cardiovascular disease among women with type 2 diabetes mellitus," by Hyun Joon Shin, MD; best resident poster, "Oral squamous cell carcinoma: current concepts in imaging, staging, and fibular osteocutaneous free flap reconstruction," by R. Evans Heithaus, MD; best medical student poster, "Neuromyelitis optica," by Elizabeth Coffee; and best oral presentation, "Transarterial chemoembolization with smaller beads: midterm clinical outcomes," by R. Evans Heithaus, MD. Overall, participants in the inaugural event presented more than 40 posters and six oral presentations. This article reprints a selection of the abstracts. PMID- 26130878 TI - Uses, limitations, and complications of endobronchial ultrasound. AB - Endobronchial ultrasound (EBUS) plays a pivotal role in the minimally invasive staging of non-small cell lung cancer. The role of EBUS is progressively expanding to include the evaluation of peribronchial lesions, pulmonary nodules, and other mediastinal abnormalities. Recently, EBUS has assisted in the diagnosis of many other disease entities, including malignancies and various infections such as tuberculosis and sarcoidosis. This article reviews the indications and contraindications of EBUS, with emphasis on the technique and complications encountered during the procedure. PMID- 26130879 TI - Recurrent hospitalization for self-injuries and suicide attempts: case study of a super-utilizer. AB - Super-utilizers, patients who amass disproportionately large occurrences of emergency department visits and hospital admissions, are increasingly recognized as a significant and potentially preventable resource consumer. A comprehensive understanding of these individuals and their situations may prove useful in preventing unnecessary admissions and improving patient care and outcomes. While most super-utilizers suffer from chronic medical issues, this patient is an unusual variant, as his super-utilization stemmed from mental health problems leading to serial self-injury. Between January 2010 and October 2014, the patient performed 49 acts of self-harm resulting in 27 acute hospital admissions and 17 additional admissions secondary to complications. In addition to documented injuries, he and his family reported up to 50 additional self-injuries since his first episode 34 years earlier. It was concluded that the patient's pattern of self-injury resulted from a combination of factors, including underlying psychiatric conditions, chronic noncompliance with medications, and potentially unavoidable behavioral reinforcement from health care professionals. PMID- 26130880 TI - Radiographic findings in the nail-patella syndrome. AB - Nail-patella syndrome is a rare disorder characterized classically by the tetrad of nail hypoplasia or aplasia, aplastic or hypoplastic patellae, elbow dysplasia, and the presence of iliac horns. Iliac horns are considered pathognomonic, and the presence of hypoplastic or aplastic patellae in conjunction with nail abnormalities is a cardinal feature of diagnosis. Elbow dysplasia is present in most cases and can exhibit features typical of the syndrome. Herein we present the radiographic findings of the elbows, knees, and pelvis of a woman with nail patella syndrome. PMID- 26130881 TI - Solitary supratentorial Listeria monocytogenes brain abscess in an immunocompromised patient. AB - We describe an 81-year-old man receiving azacitidine monotherapy for myelodysplastic syndrome who was improving from Listeria monocytogenes bacteremia after receiving antibiotic therapy during an earlier hospital admission. Shortly after discharge he developed new-onset seizure activity, with brain imaging on subsequent admissions demonstrating a posterior right frontal lobe mass. Specimen cultures after resection of the mass revealed this to be a cerebral abscess related to L. monocytogenes. Brain abscesses related to this organism are rare. PMID- 26130882 TI - Asplenia and fever. AB - A 45-year-old-man presented with the abrupt onset of a fever over 30 years after surgical splenectomy. He presented with symptoms and findings that seemed consistent with influenza. He rapidly developed fulminant meningitis that resulted in his death. PMID- 26130883 TI - Myroides odoratimimus bacteremia in a diabetic patient. AB - Myroides species are a rare source of human infection. Though not part of the human microbiota, Myroides species are commonly found in the environment. Myroides infections are typically attributed to contact with contaminated water; the most common presentation is in immunocompromised patients. We present a patient with a diabetic foot ulcer who subsequently developed Myroides odoratimimus bacteremia and bone abscess. PMID- 26130884 TI - Right-sided hydropneumothorax as a presenting symptom of Boerhaave's syndrome (spontaneous esophageal rupture). AB - Boerhaave's syndrome, or spontaneous esophageal rupture, is a rare condition that classically presents with Mackler's triad of vomiting, subcutaneous emphysema, and severe sudden onset of chest pain and requires immediate medical attention. Approximately 90% of the perforations occur at the left lateral aspect of the distal esophagus, causing a left-sided pleural effusion. Less than 10% of patients have bilateral effusions, and few patients have a right-sided pleural effusion only. We present the case of a 59-year-old man with spontaneous esophageal rupture. His clinical presentation is of interest since he had no inciting event for spontaneous esophageal rupture and had a delayed presentation with a right-sided hydropneumothorax. PMID- 26130885 TI - Pneumomediastinum in inflammatory bowel disease. AB - A 28-year-old man with a history of inflammatory bowel disease (IBD) developed sudden-onset chest pain and dyspnea 9 days after esophagogastroduodenoscopy and colonoscopy. A chest radiograph demonstrated pneumomediastinum tracking along the left heart border. The spontaneous pneumomediastinum was presumed to be a complication of his severe colitis. The severity of our patient's symptoms ultimately necessitated a subtotal colectomy, a decision unrelated to the pneumomediastinum. IBD-associated pneumomediastinum can be attributed to retroperitoneal air leakage from severe colitis and usually resolves with conservative management. PMID- 26130886 TI - Pulmonary veno-occlusive disease as a cause of pulmonary arterial hypertension. AB - Pulmonary veno-occlusive disease (PVOD) represents a rare form of precapillary pulmonary arterial hypertension. We present a young patient hospitalized with progressive dyspnea, with initial workup suggestive of pulmonary hypertension and unexplained noncardiogenic pulmonary edema. His subsequent clinical course was consistent with the diagnosis of PVOD. PMID- 26130887 TI - Pulmonary artery catheter-induced perforation treated with coil embolization. AB - The past 40 years have taught us much about the use of pulmonary artery catheters and their complications. Pulmonary artery rupture carries high morbidity and mortality, and therefore a high index of suspicion and timely management are key to the survival of patients who suffer from this rare complication. While surgical therapy has been considered the mainstay of treatment, endovascular therapy is feasible when surgery is not possible or desirable, as demonstrated in our patient. It is unknown which approach is optimal. PMID- 26130888 TI - A hybrid repair of a superior mesenteric artery pseudoaneurysm using open mesenteric bypass and endovascular exclusion. AB - Superior mesenteric artery (SMA) aneurysms and pseudoaneurysms are uncommonly encountered in vascular surgery practice, but they typically require repair. Historically, they have been repaired with open aneurysmorrhaphy, bypass and exclusion, or simple ligation. More recently, endovascular repair with coil embolization and stent graft exclusion have been advocated. We present a repair of an SMA pseudoaneurysm via a hybrid approach with common hepatic artery to SMA bypass, exclusion of the pseudoaneurysm with ligation of the SMA proximal to the bypass, plug occlusion of the proximal SMA, and coil embolization of the pseudoaneurysm. PMID- 26130889 TI - Allergic acute coronary syndrome (Kounis syndrome). AB - Anaphylaxis rarely manifests as a vasospastic acute coronary syndrome with or without the presence of underlying coronary artery disease. The variability in the underlying pathogenesis produces a wide clinical spectrum of this syndrome. We present three cases of anaphylactic acute coronary syndrome that display different clinical variants of this phenomenon. The main pathophysiological mechanism of the allergic anginal syndromes is the inflammatory mediators released during a hypersensitivity reaction triggered by food, insect bites, or drugs. It is important to appropriately recognize and treat Kounis syndrome in patients with exposure to a documented allergen. PMID- 26130890 TI - Blood cyst of the anterior mitral leaflet causing severe mitral regurgitation. AB - We report a case of blood cyst of the anterior mitral leaflet leading to severe mitral regurgitation and heart failure in a 70-year-old woman with no other factors that could explain the severe mitral regurgitation. PMID- 26130891 TI - Right-sided superior vena cava draining into the left atrium in a patient with persistent left-sided superior vena cava emptying into the right atrium diagnosed by echocardiography. AB - We present a patient with an isolated right-sided superior vena cava draining into the left atrium with a persistent left-sided superior vena cava emptying into the right atrium. During an agitated saline injection into the patient's right upper extremity intravenous line, the patient suffered an acute transient ischemic attack. To our knowledge, this is the only reported case of this rare anomaly incidentally uncovered during an echocardiogram with saline contrast study. PMID- 26130892 TI - Spontaneous coronary artery dissection in a 22-year-old man on lisdexamfetamine. AB - Spontaneous coronary artery dissection (SCAD) is a rare cause of coronary events and sudden cardiac death. SCAD can present with a wide spectrum of clinical presentations and as an entity remains underrecognized. Several risk factors, such as female gender, peripartum and early postpartum state, and atherosclerotic disease, have been attributed to SCAD. Amphetamine use has been attributed to an increased risk for coronary artery events. We present a case of a 22-year-old man on lisdexamfetamine and no other significant medical history who presented with SCAD and was successfully treated with medical management. PMID- 26130893 TI - Worsening dyspnea in a 38-year-old woman. PMID- 26130894 TI - Chronic pulmonary embolism in a young athletic woman. AB - Exercise-induced dyspnea (EID) is a common complaint in young athletes. Exercise induced bronchospasm (EIB) is the most common cause of EID in healthy athletes, but it is important to recognize more serious pathology. Herein we present the case of an 18-year-old woman with a 1.5-year history of EID. She had been treated for EIB without relief. Her arterial oxygen saturation was 88% during exercise testing. Computed tomographic angiography to assess for vascular abnormalities identified a large thrombus in the main pulmonary trunk. Symptoms markedly improved with therapeutic anticoagulation. Massive pulmonary embolus is an exceedingly rare etiology of exertional dyspnea in young athletes. Hypoxemia during exercise testing was an important clue that something more ominous was lurking that required definitive diagnosis. PMID- 26130895 TI - Nonhepatic hyperammonemic encephalopathy due to undiagnosed urea cycle disorder. AB - Ornithine transcarbamoylase deficiency is the most common inherited urea cycle disorder. In adults, its phenotypes are diverse. In asymptomatic patients with late presentations, symptom onset is often associated with a precipitating factor. We present a case of a woman with urea cycle disorder diagnosed after an acute peptic ulcer bleed and fasting. PMID- 26130896 TI - Anaplastic large-cell lymphoma in AIDS. AB - AIDS-related malignancies may alter clinical courses and result in death in critically ill patients. We present a case of a newly diagnosed AIDS patient with Pneumocystis jiroveci pneumonia, Epstein-Barr virus, and cytomegalovirus infections who was found to have widely metastatic kinase-negative anaplastic large-cell lymphoma. This case demonstrates the diversity in the malignant presentation of HIV-infected patients, outside of the more commonly observed non Hodgkin lymphomas. PMID- 26130897 TI - Primary follicular lymphoma of the duodenum. AB - Follicular lymphoma, a common nodal lymphoma, is rare in the gastrointestinal tract. When seen in this location, duodenal involvement is frequent. Most patients have localized disease, and survival appears to be excellent even without treatment. Although the outcomes are improved, the morphologic, immunophenotypic, and genetic features remain similar to those of nodal follicular lymphomas. We describe a woman with de novo follicular lymphoma of the duodenum and discuss the features of this remarkably indolent variant of follicular lymphoma. PMID- 26130898 TI - Tubulocystic carcinoma of the kidney. AB - Tubulocystic carcinoma (TCC) of the kidney is a unique, rare, and recently recognized neoplasm. Although originally considered a low-grade collecting duct carcinoma, TCC is now considered to be a distinct entity. TCC should be considered in the differential diagnosis of cystic renal neoplasms. We report a case of TCC arising in the left kidney. PMID- 26130899 TI - Unusual presentation of metastatic ovarian carcinoma as an enlarged intramammary lymph node. AB - Metastasis to the breast most commonly arises from a contralateral primary breast malignancy; however, metastatic disease can also result from extramammary malignancies by hematogenous or lymphatic dissemination. This case report reviews an unusual presentation of primary ovarian carcinoma with metastasis to an intramammary lymph node. PMID- 26130900 TI - Leukoencephalopathic changes on magnetic resonance imaging associated with a thermogenic dietary supplement (Thermatrim). AB - Acute toxic leukoencephalopathy can be caused by exposure to many compounds. Reversibility has been described in some cases with prompt recognition and withdrawal of the offending agent. Its association with a thermogenic supplement has never been reported. We describe two such cases in young women taking a commercially available thermogenic dietary supplement who presented with acute neurologic deficits and a common magnetic resonance imaging pattern. PMID- 26130901 TI - Precision medicine: hype or hoax? PMID- 26130902 TI - Update on the Baylor Scott & White Quality Alliance. PMID- 26130903 TI - Nobel laureates and their medical schools: who selected whom? PMID- 26130904 TI - On Camel Rides and Moses Maimonides. PMID- 26130905 TI - David Bruce Hellmann, MD: a conversation with the editor. PMID- 26130906 TI - Facts and ideas from anywhere. PMID- 26130907 TI - excellence in medical research - can we make it in india? PMID- 26130908 TI - peer review of grant funding - the Australian perspective. PMID- 26130909 TI - Association between Interleukin-6 (G174C and G572C) promoter gene polymorphisms and risk of ischaemic stroke: A meta-analysis. AB - BACKGROUND: Interleukin-6 (IL-6), as one of the most typical pro-inflammatory and immunoregulatory cytokines, is believed to be associated with the genesis and maintenance of inflammatory response. Genetic association studies (GAS) that have investigated the association between Interleukin 6 (G174C and G572C) promoter gene polymorphisms and susceptibility to ischemic stroke (IS) which have produced contradictory and unconvincing results. PURPOSE: The aim of this meta-analysis is to provide a relatively comprehensive account of the association of IL-6 (G174C and G572C) polymorphisms with susceptibility to IS. METHODS: A literature search was conducted using electronic database PubMed, Medline, and Trip database for all case-control studies investigating for association of IL-6 genetic polymorphisms with ischemic stroke published till August 30, 2014. The following combinations of main keywords were used: ('Interleukin-6' or 'IL-6') and ('ischaemic stroke or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for IL-6 gene-disease association. Meta-analysis was carried out using Revman 5.3 software. RESULTS: 16 case-control studies involving a total of 3,317 IS patients and 3,432 healthy controls for G174C polymorphism and 3 case-control studies with a total of 2,001 IS patients and 2,027 healthy controls for G572C IL-6 gene polymorphisms were included in a meta-analysis. For IL-6 G174C gene polymorphisms, no significant association was observed under dominant [GC + CC vs. GG: OR = 1.01, 95% CI: 0.77-1.34, P = 0. 92], recessive [CC vs. GG + GC: OR = 0.82, 95% CI: 0.40-1.70, P = 0. 59] and allelic model [C vs. G Allele: OR = 0.99, 95% CI: 0.74-1.31, P = 0. 93]. For IL-6 G572C, no significant association was observed under dominant [CC vs. GG + GC: OR = 0.99, 95% CI: 0.57-1.71, P = 0. 97], recessive [CC vs. GG + GC: OR = 0.93, 95% CI: 0.60-1.45, P = 0. 75] and allelic model [C vs. G Allele: OR = 0.95, 95% CI: 0.66-1.36, P = 0. 76]. CONCLUSION: This meta-analysis shows that IL-6 (G174C) and IL-6 (G572C) gene polymorphisms may not be associated with an increased susceptibility to IS. Further studies are required for confirmatory results. PMID- 26130910 TI - Comparative evaluation of risk factors, outcome and biomarker levels in young and old acute ischemic stroke patients. AB - BACKGROUND: Stroke is the third leading cause of death and disability worldwide accounting for 400-800 strokes per 100,000 individuals each year. PURPOSE: In the present study, we compared risk factors, clinical outcome, and prognostic biomarkers NSE, S-100 betabeta and ITIH4 levels in young and old acute ischemic stroke (AIS) patients. METHODS: We compared the risk factors and clinical outcomes in young (n = 38) and old (n = 66) AIS patients admitted to tertiary health care centre in Central India. In addition, we also evaluated NSE, S100betabeta & ITIH4 levels in admission and discharge samples of young and old AIS patients with different clinical outcome. RESULTS: Hypertension was a major risk factor in 45% of young and 80% of old AIS patients. Hospital outcome was less favorable in young AIS patients with higher dependent rates of 24% as compared to 12% in old AIS patients. Whereas long term outcome at 12 and 18 months after discharge was more favorable in young AIS patients with low dependency rates of 16% and 11% as compared to 41% and 24% in older AIS patients respectively. Similarly, serum NSE, S100betabeta and ITIH4 levels showed a distinct pattern of expression at discharge time in AIS patients with improved and dependent outcome in both the age groups. CONCLUSION: Young males with hypertension and smoking habits are at a high risk of AIS while old AIS patients are at a greater risk of worse long term outcome. Serum levels of NSE and S100betabeta are independent predictors of outcome in AIS patients. Similarly, it also suggests that serum ITIH4 levels could be used as a potential biomarker for predicting the outcome in AIS patients. PMID- 26130911 TI - The outcome after aneurysmal sub arachnoid hemorrhage: a study of various factors. AB - BACKGROUND: Aneurysmal subarachnoid hemorrhage (A-SAH), despite improvement in surgical and medical treatments, is still a serious disease with high fatality and morbidity rates. Despite the huge advances in neurosurgical management of the disease, there has not been a proportional improvement in outcome of this condition. PURPOSE: We studied various factors which can influence the final outcome and these included: World federation of neurosurgical societies (WFNS), Hunt & Hess (H&H) and Fisher grade, size of aneurysm, intra operative rupture (IOR), temporary clipping (TC) - and correlate their individual impact in final outcome. METHODS: We studied 100 patients of aneurysmal subarachnoid hemorrhage prospectively all of whom were operated upon .Post operative course was followed and final outcome studied. RESULTS: Pre operatively, higher WFNS and H&H grades had a worse outcome. This correlation was not found for Fisher grade. Nonetheless, presence of IVH(Fisher grade 4) acted as an independent risk factor for poor outcome. CONCLUSION: Diabetes and smoking led to a worse outcome in contrast to hypertension . IOR led to poor outcome while temporary clipping did not. PMID- 26130912 TI - Infectious disease screening among stem cell transplant donors: An Institutional experience in Saudi Arabia. AB - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) involves the infusion of hematopoietic stem cells from a suitable donor to a patient who has undergone chemotherapy. Stem Cell transplantation is used for the treatment for a wide variety of diseases, including leukemia and lymphoma. PURPOSE: This study highlights prevention strategies of infectious diseases among HSCT donors and recipients in our institute as guided by International guidelines. We aim to highlight the strategy for extensive screening of HIV, Hepatitis B and C, CMV infection and syphilis cases in all the stem cell units stored in our facility. METHODS: We searched the institutional database to identify cases of infectious diseases among HSC transplants. Extensive donor evaluation was conducted through screening and laboratory infectious disease testing for HIV, Hepatitis B and C, CMV infection and syphilis. RESULTS: Between 1996 and 2014, 263 consecutive adult HSCT were performed. An approximate equal number of autologous and allogeneic HSC collections were undertaken. The median age for autologous donors was 35 years, whereas that of allogeneic donors is 25 years. Of the 263 stem cell donors, we found 18 patients (autologous) and 2 donors (allogeneic) to be infected. We did not find any of the donors infected with HIV by the serology as well as the NAT testing protocol. CONCLUSION: Donor screening and testing is the most critical parameter in stem cell transplantation in order to ensure the safety of the product to be transplanted. Modifications in the regulations related to donor screening are aimed at providing safe transplantation and negate the risk of accidental infection of the donor. PMID- 26130913 TI - Inflectional versus derivational abilities of children with specific language impairment- A panorama from sequential cognition. AB - BACKGROUND: Specific Language Impairment (SLI) is a neurodevelopmental disorder affecting language acquisition in the absence of frank neurological damage, hearing deficits, severe environmental deprivation, or mental retardation. Children with SLI have significant difficulties in syntax domain of language compared to semantics, while their acquisition of pragmatics is relatively spared. PURPOSE: The purpose of the present study is to examine the judgment and revision of inflectional and derivational morphemes of children with specific language impairment (SLI). METHODS: 31 children with SLI and 33 typically developing (TD) children participated in the study (age range 8-13 years). The stimuli consisted of 18 sentences with inflectional morphemes and 18 sentences with derivational morphemes for grammatical judgment and revision tasks. Inflectional and derivational performance of SLI group was compared with TD group on judgment and revision scores. RESULTS: Children with SLI were significantly poorer compared to TD children on inflectional operations (invariably on judging & revising) but performed like TD children on derivational morphemes. Within SLI, inflectional performance was significantly poorer than derivational performance. In contrast, TD children performed better on inflections than derivations. Findings supported the predictions and discussed using possible sequencing problems in children with SLI. CONCLUSION: The study describes the findings using sequential difficulties reported by procedural deficit hypothesis (PDH) in SLI. PMID- 26130914 TI - Secreted trophic factors of Human umbilical cord stromal cells induce differentiation and neurite extension through PI3K and independent of cAMP pathway. AB - BACKGROUND: Trophic factors (TFs) play important role during development and adult tissue maintenance. In neurodegenerative diseases (ND) TF supplementation provides protection. Stromal cells (HUMS) derived from the human umbilical cord matrix provide neuroprotection in the ND models of mice. PURPOSE: Though TF mediated protection is known, the exact mechanism of protection is not clear. So, here the essential TFs (secreted by HUMS cells) and the pathway of induction of neurite extension, differentiation and networking is addressed. METHODS: The HUMS cells from the human umbilical cord matrix were derived and the mouse spinal cord motor neuron cell line, NSC-34 was extensively used. Flow cytometry, immunohistochemistry, RT- PCR, western blot, ELISA and antibody/inhibitor treatment were carried out to figure out the TF pathway. RESULTS: The HUMS cells secrete six neurotrophic factors (sTFs), namely, NT-3, NGF, BDNF, VEGF, IGF-1 and GDNF (TFs). These TFs are sufficient to induce differentiation, neurite extension and neural networking in a motor neuron cell line, NSC34. All the 5 TFs need to be neutralized simultaneously with their antibodies to abrogate neurite extension. These motor neurons express the concomitant receptors, which are either receptor tyrosine kinase (TrK) coupled or to the receptor followed by the TrKs, for the above trophic factors (except for BDNF). The tyrosine kinase inhibitor, K252a, drastically reduces neurite extension. In NSC34, the TFs are coupled to the PI3K-Akt-pathway and the RAS-MAP kinase signaling through phosphorylation of ERK1 and ERK2. PI3K inhibitor, Ly 294002, abolishes neural differentiation and neurite extension. Thus, differentiation, neurite extension and networking could be achieved through the PI3K pathway. Intriguingly, the cAMP second messenger system coupling was not required. H89, PKA-inhibitor caused extensive cell death. But, had no effect in the presence of HUMS-secreted TFs(HSTFs) suggesting a pathway switch for cell survival itself. CONCLUSION: HUMS cells and their secreted factors could be of great use in regenerative medicine (RM). The activators of PI3K pathway, the major route of these HUMS-TFs action could be explored in RM and in the neurobiology of neural differentiation and extension. PMID- 26130915 TI - Exercise training increases size of hippocampus and improves memory PNAS (2011) vol. 108 | no. 7 | 3017-3022. PMID- 26130917 TI - Good Laboratory and Research practices-Lecture series and workshop 20-09-14-IISER Mohali. PMID- 26130918 TI - Moyamoya Disease: a ray of hope from a psychosocial perspective. AB - Moyamoya disease (MMD) is a rare blood vessel disorder occurring in people from Japan and other Asian countries, but people in other countries also have been diagnosed with MMD. Impaired neuropsychological functioning is a common sequelae of MMD in children as well as adults. We report a male, diagnosed as MMD at 8 years who was referred for neuropsychological evaluation (NPE) at 12 year, revealed impaired intellectual functioning with moderate retardation on social adaptive functioning. After 2 years of follow up, post psychosocial intervention, the patient showed remarkably upward trend in his social adaptive functioning, with shift in his intellectual functioning by 21 I.Q. Points thereby brining him to mild category of mental retardation. Therefore, this rare case shows improved neuropsychological functioning, highlighting importance of interplay between nature and nurture roles. Hence, NPE is sensitive in comparing and drawing inferences for neuropsychological rehabilitation and pharmacological management for such patients. PMID- 26130916 TI - Dystrophin induced cognitive impairment: mechanisms, models and therapeutic strategies. AB - Existence of conserved domains in dystrophin and its associated complexes provide an opportunity to understand the role of dystrophin associated signalling and its association with neuronal metabolism in a variety of model organisms. We critically reviewed the studies till 2013 through established search engines and databases. Thus, we review the role of dystrophin and its isoforms in different animal models at developmental stages in the neuronal metabolism to enhance the therapeutic strategies. Dystrophin interacts with other proteins in such a way that, when affected, it results in co-morbidities including autism and other neuropsychiatric disorders. It is speculated that various signalling molecules may converge to disrupt neuronal metabolism not adequately studied. TGF-beta, RhoGAP and CAM mediated signalling molecules are the chief cause of mortalities due to respiratory and cardiac involvement but remain underevaluated targets for cognitive impairment in DMD/BMD. Manipulation of these signalling pathways could be potent intervention in dystrophin induced cognitive impairment while complementary therapeutic approaches may also be helpful in the treatment of cognitive impairment associated with DMD/BMD. PMID- 26130919 TI - comparative effectiveness research collaboration and precision medicine. PMID- 26130920 TI - perspectives on the clean India campaign, the microbiota and ayurveda. PMID- 26130921 TI - Safety of human embryonic stem cells in patients with terminal/incurable conditions- a retrospective analysis. AB - BACKGROUND: Human embryonic stem cells (hESCs) are pluripotent cells that have the potential to self-renew and differentiate into all types of human cells. PURPOSE: The present study was aimed at establishing the safety of hESC therapy in patients with terminal/incurable conditions. METHODS: This was a single cohort study conducted at Nutech Mediworld, New Delhi. The patients suffering from various degenerative diseases were included in the study from year 2002 to 2004. hESCs (0.25 mL) were injected under skin in the abdominal wall. The safety of hESC therapy was evaluated by assessing the AEs experienced by patients during the study. Any disabling symptom/ sign, teratoma or antigen-antibody reaction that a patient suffered post transplantation of hESCs was considered as an AE. RESULTS: A total of four, six and twenty three patients received hESC therapy in the year 2002, 2003 and 2004 respectively. Pain and fever were the most common AEs observed during the study. Other AEs included headache, mild pain in the abdomen, swelling of legs (edema), urinary tract infection (UTI), rash/erythema, pain at the lower back and limbs and body ache. All the AEs reported were mild in nature and resolved within one or two days with symptomatic medication and rest. No serious AEs were reported. The improvement in specific parameters of the patients was observed after the therapy. CONCLUSION: hESCs used in the present study are safe for use in humans afflicted with incurable/terminal conditions. Future, prospective controlled studies to substantiate the present study are ongoing. PMID- 26130922 TI - Caffeine/sleep-deprivation interaction in mice produces complex memory effects. AB - BACKGROUND: Sleep deprivation negatively impacts memory, causing deficits in memory processes. Of interest is any agent that can offset such deficits. Mice were given varying doses of caffeine for 14 days and then deprived of sleep for 6 hours by the 'gentle handling' method. Memory was assessed using the Novel Object Recognition Test and Y maze alternation. PURPOSE: The study was designed to ascertain the impact of varying doses of caffeine combined with total sleep deprivation on spatial and non spatial memory in mice. METHODS: Adult Swiss Webster mice of both sexes were assigned to six groups viz., vehicle (distilled water), or one of five selected doses of caffeine (10, 20, 40, 80 and 120 mg/kg) for 14 days via the oral route. Open field novel object recognition test and Y maze spatial working memory tests were carried out on day 14. Results were analysed using multi-factorial ANOVA followed by Tukey HSD test and expressed as mean +/- S.E.M, with p values less than 0.05 were considered statistically significant. RESULTS: Novel object recognition tests (NOR) revealed that pre training and pre-test sleep deprivation and caffeine combination impaired non spatial and spatial memory in male and female mice. CONCLUSION: The study shows the complex interactions with memory that may arise when total sleep deprivation is superimposed on caffeine administration. PMID- 26130923 TI - Endothelial proliferation modulates neuron-glia survival and differentiation in ischemic stress. AB - BACKGROUND: Recent studies have shown that endothelial proliferation and angiogenic response are characteristic of degenerative events, such that the magnitude of endothelial activation is reflective of the progression of neurodegeneration. PURPOSE: This study sets out to, compare, the degenerative changes seen in the parietal cortex (PC) and periventricular zone (PVZ) after cyanide toxicity or vascular occlusion. METHODS: Global vascular occlusion (VO) and cyanide toxicity (CN) were induced in separate sets of male adult wistar rats for 10 days (treatment phase). Subsequently, the treatment was discontinued for another 10 days (withdrawal phase) (CN-I and VO-I). A separate group of control was maintained for 10 days and received normal saline for this duration. The animals were euthanized at day 10 (treatment and control) and day 20 (withdrawal) after which the tissue was processed for antigen retrieval immunohistochemistry to demonstrate; H&E (general histology) CD31/PECAM 1(endothelial proliferation), CD45 (monocyte/phagocyte), GFAP (glia), NSE (neuron), Ki-67 (cell proliferation) and NF (neurofilament). Total cell count, immunopositive cell counts, arterial wall thickness and lumen width were determined and plotted using ANOVA with significance set at P<0.05*. RESULTS: We observed an increase in endothelial proliferation (?CD31), glia activation and a decrease in neuron count in vascular occlusion and cyanide toxicity after the treatment phase (degeneration). The neuron count increased (?NSE) after withdrawal of cyanide treatment and vascular occlusion and was accompanied by a corresponding decrease in endothelial and glia activation (?CD31/GFAP). Degenerative changes were more prominent in cyanide toxicity when compared with vascular occlusion. The increase in CD45 expression coupled with a reduced CD31/GFAP after the withdrawal phase was evident of vascular remodeling and neurosurvival. CONCLUSION: We conclude that neuronal degeneration in cyanide toxicity or vascular occlusion is dependent on an increase in endothelial proliferation (?CD31), glia activation (?GFAP) and a decrease in monocyte expression (?CD45); representing a pro-inflammatory response. Furthermore, cyanide toxicity induced more prominent degenerative changes when compared with the vascular occlusion due to a higher CD31/GFAP expression. Subsequent withdrawal of the ischemia facilitated a reduction in GFAP/CD31 with a corresponding increase in monocytes (?CD45) for vascular remodeling and neurosurvival. The VO-I showed a significant increase in vascular remodelling than the CN-I due to a more significant increase in monocytic expression (CD45) after the withdrawal of the occlusion. Generally, we found that degeneration was prominent in the parietal cortex and less in the periventricular zone for both forms of ischemia. PMID- 26130924 TI - Foraging enrichment modulates open field response to monosodium glutamate in mice. AB - BACKGROUND: Environmental enrichment can enhance expression of species-specific behaviour. While foraging enrichment is encouraged in laboratory animals, its impact on novelty induced behaviour remain largely unknown. PURPOSE: Here, we studied behavioural response of mice to acute and subchronic oral monosodium glutamate (MSG) in an open field with /without foraging enrichment. METHODS: Adult male mice, assigned to five groups were administered vehicle (distilled water), or one of four selected doses of MSG (10, 20, 40 and 80 mg/kg) for 21 days. Open field novelty induced behaviours i.e. horizontal locomotion, rearing and grooming were assessed after the first and last doses of MSG. Results were analysed using MANOVA followed by Tukey HSD multiple comparison test and expressed as mean +/- S.E.M. RESULTS: Following acute MSG administration without enrichment, locomotor activity reduced, grooming increased, while rearing activity reduced at lower doses and increased at higher doses. Subchronic administration without enrichment was associated with increased locomotor activity and reduction in grooming, rearing activity however still showed a biphasic response. Addition of enrichment with acute administration resulted in sustained reduction in locomotor and rearing activities with a biphasic grooming response. Subchronically, there was reduction in horizontal locomotion, biphasic rearing response and sustained increase in grooming activity. CONCLUSION: Behavioural response to varying doses of MSG as observed in the open field is affected by modifications such as foraging enrichment, which can reverse or dampen the central effects seen irrespective of duration of administration. PMID- 26130925 TI - ELISA based quantification of Pax6 expression in the developing Zebrafish embryos. AB - BACKGROUND: Transcription factors are the key regulators of metabolic pathways in the cells, tissues and organ development during embryogenesis. Pax6 is a transcription factor involved in vertebrate eye, brain and central nervous system formation during development. PURPOSE: A reliable and sensitive assay for the spatiotemporal expression, quantification and detection of Pax6 is not available so far in zebrafish as a developmental model, hence the objective of this work is to develop quantitative assay in zebrafish embryos. METHODS: The Pax6 transcription factor was purified by heparin agarose affinity chromatography and DEAE cellulose chromatography techniques from the developing zebrafish embryos. The purity was confirmed by SDS-PAGE and western blotting using Pax6 mouse monoclonal antibody. The standard graph was plotted for Pax6 and the expressions in seventeen developmental stages were quantified by indirect ELISA. RESULTS: The maximum expression of Pax6 was detected at 8 hpf (hours post fertilization) and it was quantified as 179 ng/embryo from the average total protein of 9.5 ug/embryo. The zebrafish Pax6 protein was detected as 48 kDa and confirmed by western blotting. CONCLUSION: This study paves way to quantify the level of expression of proteins or transcription factors during early embryonic and larval development or embryogenesis using zebrafish as model system. PMID- 26130926 TI - FFT transformed quantitative EEG analysis of short term memory load. AB - BACKGROUND: The EEG is considered as building block of functional signaling in the brain. The role of EEG oscillations in human information processing has been intensively investigated. PURPOSE: To study the quantitative EEG correlates of short term memory load as assessed through Sternberg memory test. METHODS: The study was conducted on 34 healthy male student volunteers. The intervention consisted of Sternberg memory test, which runs on a version of the Sternberg memory scanning paradigm software on a computer. Electroencephalography (EEG) was recorded from 19 scalp locations according to 10-20 international system of electrode placement. EEG signals were analyzed offline. To overcome the problems of fixed band system, individual alpha frequency (IAF) based frequency band selection method was adopted. The outcome measures were FFT transformed absolute powers in the six bands at 19 electrode positions. RESULTS: Sternberg memory test served as model of short term memory load. Correlation analysis of EEG during memory task was reflected as decreased absolute power in Upper alpha band in nearly all the electrode positions; increased power in Theta band at Fronto Temporal region and Lower 1 alpha band at Fronto-Central region. Lower 2 alpha, Beta and Gamma band power remained unchanged. CONCLUSION: Short term memory load has distinct electroencephalographic correlates resembling the mentally stressed state. This is evident from decreased power in Upper alpha band (corresponding to Alpha band of traditional EEG system) which is representative band of relaxed mental state. Fronto-temporal Theta power changes may reflect the encoding and execution of memory task. PMID- 26130927 TI - Poly (ADP-Ribose) Polymerase-1 causes mitochondrial damage and neuron death mediated by Bnip3, J Neurosci. 2014 Nov 26;34(48):15975-87. PMID- 26130929 TI - Asia ARVO 2015 Report. PMID- 26130928 TI - Obesity and deep brain stimulation: an overview. AB - Deep brain stimulation (DBS) has been employed to treat a variety of disorders such as Parkinson disease, dystonia, and essential tremor. Newer indications such as epilepsy and obsessive-compulsive disorder have been added to the armamentarium. In this review, we present an initial summary of current methods in the management of obesity and then explore efforts in neuromodulation and DBS as a novel modality in the treatment of obesity disorders. PMID- 26130931 TI - [Not Available]. PMID- 26130930 TI - Cobb syndrome: A rare cause of paraplegia. AB - Cobb syndrome is an exceedingly rare clinical condition defined by the presence of a vascular skin nevus and an angioma in the spinal canal at the same metamere. We report the case of a 14-year-old boy who presented with sudden onset paraplegia. Physical examination showed port-wine stains over buttock and thigh. Magnetic resonance (MR) angiogram of the dorso-lumbar spine revealed a large arteriovenous malformation (AVM) at D11-D12 to L2-L3 levels. These concurrent findings led to the diagnosis of Cobb's syndrome. The patient received orally administered prednisolone therapy and underwent endovascular embolization of spinal angioma. Cobb's syndrome is a rare disease entity and literature search revealed only a few case reports and series mentioning this condition to date. The importance lies in the recognition that cutaneous vascular lesions may clue to an associated spinal cord angioma or AVM that may lead to weakness or paralysis. PMID- 26130932 TI - Cassia fistula Linn: Potential candidate in the health management. AB - Cassia fistula Linn is known as Golden shower has therapeutics importance in health care since ancient times. Research findings over the last two decade have confirmed the therapeutics consequence of C. fistula in the health management via modulation of biological activities due to the rich source of antioxidant. Several findings based on the animal model have confirmed the pharmacologically safety and efficacy and have opened a new window for human health management. This review reveals additional information about C. fistula in the health management via in vivo and in vitro study which will be beneficial toward diseases control. PMID- 26130934 TI - Extraction and elemental analysis of Coleus forskohlii extract. AB - BACKGROUND: Coleus forskohlii Willd. is a popular traditional medicine used since ancient times for treatment of heart diseases, abdominal colic and respiratory disorders. OBJECTIVE: The aim of this study was to characterize the root extract of the medicinal plant Coleus forskohlii. MATERIALS AND METHODS: Dry roots of C. forskohlii were used to extract Forskolin using toluene as a solvent. Thus, obtained extract of C. forskohlii was standardized to 30% and used for further studies. RESULTS: The physical properties of the extract were analyzed through scanning electron microscopy analysis, while the characterization of root extract through X-ray diffraction (XRD) and element analysis. The morphological feature of the C. forskohlii extract showed a flake like structure and the XRD showed sulfur trioxide (SO3) and trimer of sulfur trioxide (S3 O9). Through element analysis, elements such as carbon, oxygen, magnesium, aluminum, silicon, phosphorous, and sulfur were identified. Carbon showed the highest weight of 75.49% in comparison to all other elements. PMID- 26130933 TI - Review of clinical studies of Polygonum multiflorum Thunb. and its isolated bioactive compounds. AB - Polygonum multiflorum Thunb. (PMT), officially listed in the Chinese Pharmacopoeia, is one of the most popular perennial Chinese traditional medicines known as He shou wu in China and East Asia, and as Fo-ti in North America. Mounting pharmacological studies have stressed out its key benefice for the treatment of various diseases and medical conditions such as liver injury, cancer, diabetes, alopecia, atherosclerosis, and neurodegenerative diseases as well. International databases such as PubMed/Medline, Science citation Index and Google Scholar were searched for clinical studies recently published on P. multiflorum. Various clinical studies published articles were retrieved, providing information relevant to pharmacokinetics-pharmacodynamics analysis, sleep disorders, dyslipidemia treatment, and neurodegenerative diseases. This review is an effort to update the clinical picture of investigations ever carried on PMT and/or its isolated bio-compounds and to enlighten its therapeutic assessment. PMID- 26130935 TI - Quantitative analysis of the nutritional components in leaves and seeds of the Persian Moringa peregrina (Forssk.) Fiori. AB - BACKGROUND: Moringa peregrina (M. peregrina) is an important tropical tree recognized for its nutritional and medicinal properties. The objective of this study was to investigate the nutritional component in the leaves and seeds of the Persian M. peregrina (Forssk.) Fiori. MATERIALS AND METHODS: The M. peregrina leaves and seeds of wild cultivated trees were collected from the areas of arid environment located in the South-East of the Iran. The leaves and seeds of M. peregrina were dried and grounded to a fine powder and kept in dark for the day of experiment. The acidic digested leaves and seeds were analyzed for Vitamins C and A, calcium, and potassium using atomic adsorption and flame emission spectrophotometer. RESULTS: The analytical data revealed that the leaves and seeds of the Persian M. peregrina (Forssk.) Fiori contain sufficient amounts of Vitamin C: 83 +/- 0.5 and 14 +/- 0.6 mg/100 g/DW; and Vitamin A: 6.8 +/- 0.7 and 24.8 +/- 0.7 mg/100 g/DW, respectively. The elemental analysis in the leaves and seeds showed that the calcium content are 764.8 +/- 1.6 and 1164.8 +/- 43.4 mg/100 g/DW and for potassium content are 900.2 +/- 14 and 572 +/- 10 mg/100 g/DW, respectively. CONCLUSIONS: The nutritional characteristics of the Persian M. peregrina (Forssk.) Fiori, investigated in this study revealed that, daily use of leaves and seeds of this plant could significantly provide the recommended dietary allowance for the Vitamins C and A, and minerals, such as calcium and potassium. PMID- 26130936 TI - Chemopreventive effect of methanolic extract of Azadirachta indica on experimental Trypanosoma brucei induced oxidative stress in dogs. AB - INTRODUCTION: The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. MATERIALS AND METHODS: Twenty-five apparently healthy dogs weighing between 3 and 8 kg were randomly divided into five groups with five dogs in each group. Ameliorative effect of A. indica on erythrocyte antioxidant status and markers of oxidative stress were assessed. Liver and kidney function tests were also performed. RESULTS: Pre-treatment with methanolic extract of Azadirachta indica (MEAI) at different doses did not significantly alter the values of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity in Trypanosoma brucei infection. Although, serum creatinine significantly (P < 0.05) decreased with pre-treatment with 50 mg/kg A. indica, after 2 weeks of T. brucei infection. However, the reduced glutathione (GSH) content of the erythrocyte increased significantly in animals pre-treated with 50 mg/kg and 200 mg/kg of A. indica respectively. Markers of oxidative stress such as malondialdehyde and hydrogen peroxide generated were higher in animals infected with T. brucei with no significant (P >0.05) difference compared to the values obtained in pre treated animals. Pre-treatment with 100 mg/kg and 200 mg/kg of A. indica significantly (P < 0.05) decreased serum myeloperoxidase activity at 2 weeks post infection with T. brucei. CONCLUSION: From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection. PMID- 26130937 TI - Study of colouring effect of herbal hair formulations on graying hair. AB - OBJECTIVE: To screen the hair colouring properties of hair colorants/ herbal hair colouring formulations. MATERIALS AND METHODS: The dried aqueous herbal extracts of Gudhal leaves (Hibiscus rosa-sinensis), Jatamansi rhizome (Nardostachys jatamansi), Kuth roots (Saussurea lappa), Kattha (Acacia catechu), Amla dried fruit (Embelica officinalis), were prepared. Coffee powder (Coffea arabica) and Henna powder (Lowsonia inermis) were taken in the form of powder (# 40). Fourteen herbal hair colorants were prepared from these dried aqueous herbal extracts and powders. Activities of hair colorants were observed on sheep wool fibers. On the basis of the above observation six hair colorants were selected. These six formulations were taken for trials on human beings. OBSERVATION: The formulation coded HD-3 gave maximum colouring effect on sheep wool fibers as well as on human beings and percentage of acceptance among the volunteers were in the following order: HD- 3 > HD- 4 > HD-1 > HD-13 > HD-14 > HD-11. RESULTS AND DISCUSSION: The remarkable results were obtained from five herbal hair colorants, viz., HD-1, HD- 3, HD- 4, HD-13 and HD-14 on sheep wool fibers and human beings. Formulation HD 3, having gudhal, jatamansi, kuth, kattha, amla, coffee and henna, was the maximum accepted formulation and suggested that these herbs in combination acts synergistically in hair colouring action. It also concluded that jatamansi, present in different hair colorants, was responsible to provide maximum blackening on hair. PMID- 26130938 TI - Evaluation of antiviral activity of essential oil of Trachyspermum Ammi against Japanese encephalitis virus. AB - BACKGROUND: Japanese encephalitis is a leading form of viral encephalitis, prevalent mostly in South Eastern Asia caused by Japanese encephalitis virus (JEV). It is transmitted by the mosquitoes of the Culex sp. The disease affects children and results in 50% result in permanent neuropsychiatric disorder. There arises a need to develop a safe, affordable, and potent anti-viral agent against JEV. This study aimed to assess the antiviral activity of ajwain (Trachyspermum ammi: Umbellifereae) essential oil against JEV. MATERIALS AND METHODS: Ajwain oil was extracted by distillation method and in vitro cytotoxicity assay was performed in vero cell line by 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) assay method. JEV titer was determined by plaque assay and in vitro antiviral activity of ajwain oil was quantified by the plaque reduction neutralization test (PRNT). RESULTS: Cytotoxic concentration of the oil was found to be 1 mg/ml by MTT assay. The titer of the virus pool was found to be 50* 10(7) PFU/ml. we observed 80% and 40% virus inhibition in 0.5mg/ml of ajwain oil by PRNT method in preexposure treatment and postexposure treatment (antiviral activity), respectively. CONCLUSION: Our data indicate ajwain oil has potential in vitro antiviral activity against JEV. Further, the active biomolecule will be purified and evaluated for anti-JEV activity and also to scale up for in vivo trial to evaluate the efficacy of ajwain oil in future. PMID- 26130939 TI - Gastrointestinal protective efficacy of Kolaviron (a bi-flavonoid from Garcinia kola) following a single administration of sodium arsenite in rats: Biochemical and histopathological studies. AB - BACKGROUND: Arsenic intoxication is known to produce symptoms including diarrhea and vomiting, which are indications of gastrointestinal dysfunction. OBJECTIVE: We investigated whether Kolaviron (KV) administration protected against sodium arsenite (NaAsO2)-induced damage to gastric and intestinal epithelium in rats. MATERIALS AND METHODS: Control rats (Group I) were given a daily oral dose of corn oil. Rats in other groups were given a single dose of NaAsO2 (100 mg/kg; intraperitoneal) alone (Group II) or after pretreatment for 7 days with KV at 100 mg/kg (Group III) and 200 mg/kg (Group IV). Rats were sacrificed afterward and portions of the stomach, small intestine and colon were processed for histopathological examination. Hydrogen peroxide, reduced glutathione, malondialdehyde (MDA) concentrations as well as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione S transferase (GST) and myeloperoxidase (MPO) were measured in the remaining portions of the different gastrointestinal tract (GIT) segments. RESULTS: NaAsO2 caused significant increases (P < 0.05) in MDA levels and MPO activity, with significant reductions (P < 0.05) in GST, GPX, CAT and SOD activities in the stomach and intestines. KV significantly reversed the changes (P < 0.05) in a largely dose-dependent manner. The different segments had marked inflammatory cellular infiltration, with hyperplasia of the crypts, which occurred to much lesser degrees with KV administration. CONCLUSION: The present findings showed that KV might be a potent product for mitigating NaAsO2 toxicity in the GIT. PMID- 26130940 TI - Are herbal mouthwash efficacious over chlorhexidine on the dental plaque? AB - AIM: To compare the effect of herbal extract mouthwash and chlorhexidine mouthwash on the dental plaque level. MATERIALS AND METHODS: The subjects (60 healthy medical students aged ranges between 20 and 25 years) were randomly divided into two groups, that is, the herbal group and the chlorhexidine gluconate mouthwash group. The data were collected at the baseline and 3 days. The plaque was disclosed using erythrosine disclosing agent and their scores were recorded using the Quigley and Hein plaque index modified by Turesky-Gilmore Glickman. Statistical analysis was carried out later to compare the effect of all the two groups. RESULTS: Our result showed that the chlorhexidine group shows a greater decrease in plaque score followed by herbal extract, but the result was statistically insignificant. CONCLUSION: The results indicate that herbal mouthwash may prove to be an effective agent owing to its ability to reduce plaque level, especially in low socioeconomic strata. PMID- 26130942 TI - Better Understanding on MERS Corona Virus Outbreak in Korea. PMID- 26130941 TI - Structural elucidation of chemical constituents from Benincasa hispida seeds and Carissa congesta roots by gas chromatography: Mass spectroscopy. AB - BACKGROUND: Benincasa hispida (BH) and Carissa congesta (CC) are regarded as ethnopharmacological imperative plants in Asian countries. OBJECTIVE: Phytochemical screening of the extracts has shown the presence of steroids, flavonoids, saponins, glycosides, tannins, phenolic compounds, fixed oils, and fats in the BH and CC extracts. The presence of lupeol has been reported previously by us using high-performance thin-layer chromatography and high performance liquid chromatography. MATERIALS AND METHODS: Present research studies encompasses identification of chemical constituents in BH seeds and CC roots petroleum ether extracts by hyphenated technique such as gas chromatography mass spectroscopy (MS) which when coupled gives a clear insight of constituents. RESULTS: The components were identified by matching mass spectra with MS libraries. There were 13 and 10 different compounds analyzed from CC and BH, respectively. The components present were Pentanoic acid, 5-hydroxy, 2,4 butylphenyl; n-Hexadecanoic acid (Palmitic acid); Sulfurous acid, 2 ethylhexylhepatdecyl ester; n-Tridecane; 6-methyltridecane; (9E, 12E)-9,12 Octadecadienyl chloride, Hexadecanoic acid, 3-(trimethylsilyl)-oxy] propyl ester; 9,12-Octadecadenoic acid, 2 hydroxy-1-(hyroxymethylethyl) ester; 9,12 Octadecadienoic acid, 2,3 dihydroxypropyl ester; n-Propyl-9,12-Octadecadienoate, Lupeol; Taraxasterol; 6a, 14a-Methanopicene, perhydro-12,4a, 61a, 9,9,12a hepatmethyl-10-hydoxy and 9-Octadecene; 2-Isoprpenyl-5-methyl-6-hepten-1-ol; n Hexadecanoic acid, 2-hyroxy-1-(hydroxymethyl) ethyl ether; Butyl-9,12 Octadecadieonate; Friedoolean-8-en-3-one; friedours-7-en-3-one; 13,27-Cyclosuran 3-one; Stigmaste-7,25-dien-3-ol (3beta, 5alpha); Stigmasta-7,16-dien-3-ol; chrondrillasterol in BH seeds and CC roots extracts respectively. CONCLUSION: Eluted components from the extracts could provide further researchers to work with various pharmacological activities related models and studies. PMID- 26130944 TI - Applying the RE-AIM Framework to Evaluate the Dissemination and Implementation of Clinical Practice Guidelines for Sexually Transmitted Infections. AB - Clinical practice guidelines (CPG) are one of the most effective ways to translate evidence of medical improvement into everyday practice. This study evaluated the dissemination and implementation of the Sexually Transmitted Infections-Korean Guidelines (STIKG) by applying the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework. A survey questionnaire was administered to clinicians via the internet. Among the 332 respondents, 190 (57.2%) stated that they were aware of STIKG and 107 (33.2%) implemented STIKG in their practice. The odds that a physician was exposed to STIKG (dissemination) were 2.61 times greater among physicians with previous training or education for any CPG than those who did not. Clinicians who indicated that STIKG were easy to understand were 4.88 times more likely to implement STIKG in their practice than those who found them not so easy. When a clinician's workplace had a supporting system for CPG use, the odds of implementation was 3.76 times higher. Perceived level of effectiveness of STIKG did not significantly influence their implementation. The findings of this study suggest that, ultimately, knowing how to engage clinicians in CPG implementation is as important as how to disseminate such guidelines; moreover, easy-to-use guidelines and institutional support are key factors. PMID- 26130943 TI - The Role of Robotic Surgery for Rectal Cancer: Overcoming Technical Challenges in Laparoscopic Surgery by Advanced Techniques. AB - The conventional laparoscopic approach to rectal surgery has several limitations, and therefore many colorectal surgeons have great expectations for the robotic surgical system as an alternative modality in overcoming challenges of laparoscopic surgery and thus enhancing oncologic and functional outcomes. This review explores the possibility of robotic surgery as an alternative approach in laparoscopic surgery for rectal cancer. The da Vinci(r) Surgical System was developed specifically to compensate for the technical limitations of laparoscopic instruments in rectal surgery. The robotic rectal surgery is associated with comparable or better oncologic and pathologic outcomes, as well as low morbidity and mortality. The robotic surgery is generally easier to learn than laparoscopic surgery, improving the probability of autonomic nerve preservation and genitourinary function recovery. Furthermore, in very complex procedures such as intersphincteric dissections and transabdominal transections of the levator muscle, the robotic approach is associated with increased performance and safety compared to laparoscopic surgery. The robotic surgery for rectal cancer is an advanced technique that may resolve the issues associated with laparoscopic surgery. However, high cost of robotic surgery must be addressed before it can become the new standard treatment. PMID- 26130945 TI - Factors That Predict Persistent Smoking of Cancer Survivors. AB - We conducted this cross-sectional study to elucidate factors that predict persistent smoking of the Korean cancer survivors. The subjects were 130 adult (>=19 yr old) cancer survivors who were smokers at the diagnosis of cancer and have participated in the Korean National Health and Nutrition Examination Surveys conducted from 2007 to 2011. We categorized them into the persistent smokers and the quitters, according to change in smoking status between the time of cancer diagnosis and the time of the survey. Factors associated with persistent smoking were evaluated using the multiple logistic regression analysis. During 7.52 yr (standard deviation = 0.34) after the cancer diagnosis, 59.6% of the 130 cancer survivors have continued to smoke. After adjusting for covariates, following factors were independently associated with the risk of persistent smoking: female, low income, high-risk alcohol use, high body mass index (>= 25 kg/m(2)), presence of household members who smoke, and longer duration of smoking. Alcohol Use Disorders Identification Test showed a positive association with the risk of persistent smoking (P for trend = 0.012). In conclusion, more efforts for smoking cessation should be in place for the cancer survivors with those risk factors associated with the persistent smoking. PMID- 26130946 TI - APOE Polymorphism Is Associated with C-reactive Protein Levels but Not with White Blood Cell Count: Dong-gu Study and Namwon Study. AB - We evaluated the association of the APOE polymorphism with serum C-reactive protein levels and white blood cell count in two large population-based studies in Korean. The datasets included the Dong-gu study (n = 8,893) and the Namwon Study (n = 10,032). APOE genotypes were identified by polymerase chain reaction restriction fragment length polymorphism. Multivariable linear regression analysis was performed to evaluate the relationship of APOE genotypes with C reactive protein levels and white blood cell count with adjustments for age, sex, body mass index, smoking, diabetes, hypertension, and serum lipids. In the multivariate model, carriers of E3E4 or E4E4 genotype had significantly lower C reactive protein levels compared with carriers of E3E3 genotype group (0.50 mg/L vs. 0.67 mg/L; 0.37 mg/L vs. 0.67 mg/L, respectively, for the Dong-gu Study and 0.47 mg/L vs. 0.66 mg/L; 0.45 mg/L vs. 0.66 mg/L, respectively, for the Namwon Study). However, there was no difference in white blood cell count among APOE genotypes. We found that the APOE E4 allele is associated with lower C-reactive protein levels, but not white blood cell count. Our results suggest that APOE genotype may influence C-reactive protein levels through non-inflammatory pathway. PMID- 26130947 TI - Identification of Outer Membrane Vesicles Derived from Orientia tsutsugamushi. AB - Orientia tsutsugamushi, a causative pathogen of Scrub typhus, is a gram-negative intracellular bacterium. Outer membrane vesicles (OMVs) are produced from the membrane of bacteria and play many roles related to the survival of the pathogen. However, there have been no reports confirming whether O. tsutsugamushi indeed produce OMVs. O. tsutsugamushi boryong was cultured in ECV-304 cells for the purification of OMVs. Western blot analysis and immunoenrichment using anti-O. tsutsugamushi monoclonal antibody and electron microscopy were employed for identification and characterization of OMVs. We confirm the presence of OMVs derived from O. tsutsugamushi, and also found that those OMVs contain a major surface antigen of 56-kDa protein and variant immunogenic antigens. PMID- 26130948 TI - Impact of Implementation of an Automated Liquid Culture System on Diagnosis of Tuberculous Pleurisy. AB - This study was conducted to evaluate the impact of implementation of an automated liquid culture system on the diagnosis of tuberculous pleurisy in an HIV uninfected patient population. We retrospectively compared the culture yield, time to positivity, and contamination rate of pleural effusion samples in the BACTEC Mycobacteria Growth Indicator Tube 960 (MGIT) and Ogawa media among patients with tuberculous pleurisy. Out of 104 effusion samples, 43 (41.3%) were culture positive on either the MGIT or the Ogawa media. The culture yield of MGIT was higher (40.4%, 42/104) than that of Ogawa media (18.3%, 19/104) (P<0.001). One of the samples was positive only on the Ogawa medium. The median time to positivity was faster in the MGIT (18 days, range 8-32 days) than in the Ogawa media (37 days, range 20-59 days) (P<0.001). No contamination or growth of nontuberculous mycobacterium was observed on either of the culture media. In conclusion, the automated liquid culture system could provide approximately twice as high yields and fast results in effusion culture, compared to solid media. Supplemental solid media may have a limited impact on maximizing sensitivity in effusion culture; however, further studies are required. PMID- 26130949 TI - Clinical Outcome of Remnant Thyroid Ablation with Low Dose Radioiodine in Korean Patients with Low to Intermediate-risk Thyroid Cancer. AB - Radioiodine activity required for remnant thyroid ablation is of great concern, to avoid unnecessary exposure to radiation and minimize adverse effects. We investigated clinical outcomes of remnant thyroid ablation with a low radioiodine activity in Korean patients with low to intermediate-risk thyroid cancer. For remnant thyroid ablation, 176 patients received radioiodine of 1.1 GBq, under a standard thyroid hormone withdrawal and a low iodine diet protocol. Serum levels of thyroid stimulating hormone stimulated thyroglobulin (off-Tg) and thyroglobulin-antibody (Tg-Ab), and a post-therapy whole body scan (RxWBS) were evaluated. Completion of remnant ablation was considered when there was no visible uptake on RxWBS and undetectable off-Tg (<1.0 ng/mL). Various factors including age, off-Tg, and histopathology were analyzed to predict ablation success rates. Of 176 patients, 68.8% (n = 121) who achieved successful remnant ablation were classified into Group A, and the remaining 55 were classified into Group B. Group A presented with significantly lower off-Tg at the first radioiodine administration (pre-ablative Tg) than those of Group B (1.2 +/- 2.3 ng/mL vs. 6.2 +/- 15.2 ng/mL, P = 0.027). Pre-ablative Tg was the only significant factor related with ablation success rates. Diagnostic performances of pre-ablative Tg < 10.0 ng/mL were sensitivity of 99.1%, specificity of 14.0%, positive predictive value of 71.1%, and negative predictive value of 87.5%, respectively. Single administration of low radioiodine activity could be sufficient for remnant thyroid ablation in patients with low to intermediate-risk thyroid cancer. Pre-ablative Tg with cutoff value of 10.0 ng/mL is a promising factor to predict successful remnant ablation. PMID- 26130950 TI - JAK2 V617F, MPL, and CALR Mutations in Korean Patients with Essential Thrombocythemia and Primary Myelofibrosis. AB - Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease. PMID- 26130951 TI - Comparison of Angiographic Outcomes of Side Branch Ostium at Bifurcation Coronary Lesion between Two-stent and One-stent Techniques. AB - Although the favored strategy for coronary bifurcation intervention is stenting main vessel with provisional side branch (SB) stenting, we occasionally use two stent strategy. The objective of this study was to investigate the angiographic outcome of SB ostium in two-stent group, compared with one-stent group. We analyzed 199 patients with bifurcation lesion who underwent percutaneous coronary intervention (PCI) with drug-eluting stent and follow up angiography. The patients were divided into one-stent group (167 lesions, 158 patients) and two stent group (41 lesions, 41 patients). Prior to intervention, SB ostium minimal luminal diameter (MLD) was smaller in two-stent group than in one-stent group (1.08+/-0.55 mm vs. 1.39+/-0.60 mm; P=0.01). But, immediately after PCI, SB MLD of two-stent group became greater than that of one-stent group (2.41+/-0.40 mm vs. 1.18+/-0.68 mm; P<0.01). Six to nine months after PCI, this angiographic superiority in SB MLD of two-stent group persisted (1.56+/-0.71 mm vs. 1.13+/ 0.53 mm; P<0.01), although there was larger late loss in two-stent group (0.85+/ 0.74 mm vs. 0.05+/-0.57 mm; P<0.01). In terms of target lesion revascularization and target vessel revascularization rates, one-stent group showed better results than two-stent group. We could attain wider long term SB ostium after two-stent strategy than after one-stent strategy. PMID- 26130952 TI - Long-term Prognosis of Paroxysmal Atrial Fibrillation and Predictors for Progression to Persistnt or Chronic Atrial Fibrillation in the Korean Population. AB - Little is known about the long-term prognosis of or predictors for the different clinical types of atrial fibrillation (AF) in Korean populations. The aim of this study was to validate a risk stratification to assess the probability of AF progression from paroxysmal AF (PAF) to persistent AF (PeAF) or permanent AF. A total of 434 patients with PAF were consecutively enrolled (mean age; 71.7 +/- 10.7 yr, 60.6% male). PeAF was defined as episodes that are sustained > 7 days and not self-terminating, while permanent AF was defined as an ongoing long-term episode. Atrial arrhythmia during follow-up was defined as atrial premature complex, atrial tachycardia, and atrial flutter. During a mean follow-up of 72.7 +/- 58.3 months, 168 patients (38.7%) with PAF progressed to PeAF or permanent AF. The mean annual AF progression was 10.7% per year. In univariate analysis, age at diagnosis, body mass index, atrial arrhythmia during follow-up, left ventricular ejection fraction, concentric left ventricular hypertrophy, left atrial diameter (LAD), and severe mitral regurgitation (MR) were significantly associated with AF progression. In multivariate analysis, age at diagnosis (P = 0.009), atrial arrhythmia during follow-up (P = 0.015), LAD (P = 0.002) and MR grade (P = 0.026) were independent risk factors for AF progression. Patients with younger age at diagnosis, atrial arrhythmia during follow-up, larger left atrial chamber size, and severe MR grade are more likely to progress to PeAF or permanent AF, suggesting more intensive medical therapy with close clinical follow-up would be required in those patients. PMID- 26130954 TI - Disease-specific Growth Charts of Marfan Syndrome Patients in Korea. AB - Patients with Marfan syndrome (MFS) presents with primary skeletal manifestations such as tall stature, chest wall abnormality, and scoliosis. These primary skeletal manifestations affect the growth pattern in MFS. Therefore, it is not appropriate to use normal growth charts to evaluate the growth status of MFS. We aimed to develop disease-specific growth charts for Korean MFS patients and to use these growth charts for understanding the growth patterns in MFS and managing of patients with MFS. Anthropometric data were available from 187 males and 152 females with MFS through a retrospective review of medical records. Disease specific growth charts were generated and 3, 25, 50, 75, and 97 percentiles were calculated using the LMS (refers to lambda, MU, and sigma, respectively) smoothing procedure for height and weight. Comparisons between MFS patients and the general population were performed using a one-sample t-test. With regard to the height, the 50th percentile of MFS is above the normative 97th percentile in both genders. With regard to the weight, the 50 percentile of MFS is above the normative 75th percentile in male and between the normative 50th percentile and the 75th percentile in female. The disease-specific growth charts for Korean patients with MFS can be useful for monitoring growth patterns, planning the timing of growth-reductive therapy, predicting adult height and recording responses to growth-reductive therapy. PMID- 26130953 TI - The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction. AB - The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF <= 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age >= 75 yr, Killip class >= III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high sensitivity C-reactive protein >= 2.59 mg/L, LVEF <= 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF <= 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR. PMID- 26130955 TI - Objective Assessment of Surgical Restaging after Concurrent Chemoradiation for Locally Advanced Pancreatic Cancer. AB - The role of neoadjuvant chemoradiation therapy in locally advanced pancreatic cancer (LAPC) is still controversial. The aim of this study was to evaluate surgical downstaging after concurrent chemoradiation therapy (CCRT) for LAPC by measuring the objective changes after treatment. From January 2003 through July 2011, 54 patients with LAPC underwent neoadjuvant CCRT. Computed tomography findings of the tumor size, including major vessel invasion, were analyzed before and after CCRT. Among the total recruited patients, 14 had borderline resectable malignancy and another 40 were unresectable before CCRT. After CCRT, a partial response was achieved in four patients. Stable disease and further disease progression were achieved in 36 and 14 patients, respectively. Tumor size showed no significant difference before and after CCRT (3.6 +/- 1.1 vs. 3.6 +/- 1.0 cm, P = 0.61). Vessel invasion showed improvement in two patients, while 13 other patients showed further tumor progression. Thirty-nine patients with unresectable malignancy and 11 patients with borderline resectable malignancy at time of initial diagnosis remained unchanged after CCRT. Four patients with borderline pancreatic malignancy progressed to an unresectable stage, whereas one unresectable pancreatic malignancy improved to a borderline resectable stage. Only one patient with borderline resectable disease underwent operation after CCRT; however, curative resection failed due to celiac artery invasion and peritoneal seeding. The adverse events associated with CCRT were tolerable. In conclusion, preoperative CCRT in LAPC rarely leads to surgical downstaging, and it could lower resectability rates. PMID- 26130956 TI - Effect of Prophylactic Palivizumab on Admission Due to Respiratory Syncytial Virus Infection in Former Very Low Birth Weight Infants with Bronchopulmonary Dysplasia. AB - The aim of this study was to observe the effects of prophylactic palivizumab on hospitalization secondary to respiratory syncytial virus (RSV) infection (RSVhospitalization) in former very low birth weight infants (VLBWI) with bronchopulmonary dysplasia (BPD). This study also sought to identify the risk factors of RSVhospitalizationin this particular infant population. A prospective observational study was conducted between September 2007 and April 2008 in seven Korean hospitals. Children with a history of very low birth weight, a diagnosis of BPD and who were <2 yr old at the onset of the RSV season were included in this study. Palivizumab injections were administered monthly for a maximum of five months during the RSV season. RSVhospitalization rates were reviewed, and RSVhospitalization rates between subgroups were categorized by gestational age, birth weight, and duration of ventilator care. A total of 90 subjects completed the follow-up interviews. The mean gestational age at birth was 26.1+/-1.7 weeks, and the mean birth weight was 889.4+/-222.2 g. The incidence of RSVhospitalization in the study population was 8.9% (8/90), and the mean hospital stay was 11.0+/-5.5 days, including one death. There were no statistically significant differences in the patients' demographic characteristics or risk factors for RSV hospitalization. When subgroup analyses were conducted, there were still no statistically significant differences. The administration of palivizumab prophylaxis during the entire RSV season is important in VLBWI with BPD, regardless of their gestational age and birth weight, or previous ventilator dependency. PMID- 26130957 TI - Pathologic Outcomes in Men with Low-risk Prostate Cancer Who Are Potential Candidates for Contemporary, Active Surveillance Protocols. AB - The purpose of this study was to determine whether contemporary active surveillance (AS) protocols could sufficiently discriminate significant from indolent tumors in men with low-risk prostate cancer. We retrospectively analyzed 312 patients with low-risk prostate cancer treated with radical prostatectomy. After exclusion of patients with fewer than 10 cores taken at biopsy and those who received neo-adjuvant treatment, 205 subjects satisfied the final inclusion criteria. Five widely accepted AS protocols were employed in this study. A total of 82.0% of the patients met the inclusion criteria of at least one protocol, and 18% did not meet any criteria of published AS protocols. A significant proportion of patients had non-organ-confined disease (8.6% to 10.6%) or a Gleason score of 7 or greater (18.6% to 23.9%) between the different AS criteria. Among patients who did not meet any AS criteria, 32.4% of patients had a pathologically insignificant cancer. Our results indicated a significant adverse pathology in patients who met the contemporary AS protocols. On the other hand, some patients in whom expectant management would be appropriate did not meet any criteria of published AS protocols. None of the clinical or histological criteria reported to date is able to sufficiently discriminate aggressive tumors from indolent ones. PMID- 26130958 TI - Lower Levels of Human MOB3B Are Associated with Prostate Cancer Susceptibility and Aggressive Clinicopathological Characteristics. AB - Mps one binder (MOB) proteins are integral components of signaling pathways that control important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation. However, the biochemical and cellular functions of the human MOB (hMOB) protein family remain largely unknown. The present study investigated the association between hMOB3B expression and clinicopathological characteristics of prostate cancer (PCa).Study subjects included 137 PCa patients and 137 age-matched benign prostatic hyperplasia (BPH) patients. hMOB3B expression was estimated using real-time PCR and compared with clinicopathological parameters of PCa. hMOB3B mRNA expression was significantly lower in PCa tissues than in BPH control tissues (P<0.001). According to receiver operating characteristics curve analysis, the sensitivity of hMOB3B expression for PCa diagnosis was 84.7%, with a specificity of 86% (AUC=0.910; 95% CI=0.869 0.941; P<0.001). hMOB3B expression was significantly lower in patients with elevated prostate specific antigen (PSA) levels (>=10 ng/mL), a Gleason score>=8, and metastatic disease (any T, N+/M+) than in those with low PSA levels, a low Gleason score, and non-metastatic disease (each P<0.05). In conclusion, low levels of hMOB3B are closely associated with aggressive clinicopathologic features in patients with PCa. Our results suggest that hMOB3B may act as a tumor suppressor in human PCa. PMID- 26130959 TI - Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-kappaB (NF-kappaB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-kappaB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases. PMID- 26130960 TI - Knowledge and Attitude of 851 Nursing Personnel toward Depression in General Hospitals of Korea. AB - Our study aimed to examine the knowledge and attitude of nursing personnel toward depression in general hospitals of Korea. A total of 851 nursing personnel enrolled at four university-affiliated general hospitals completed self-report questionnaires. Chi-square tests were used to compare the knowledge and attitude of registered or assistant nurses toward depression. In addition, binary logistic regression analysis was used to adjust for the following confounders: age-group and workplace. Registered and assistant nurses differed in their knowledge and attitude toward depression. The proportion of rational and/or correct responses were higher in registered nurses than assistant nurses for the following: constellation of depressive symptoms defined by DSM-IV (adjusted odds ratio [aOR], 3.876; P<0.001); suicide risk in depression recovery (aOR, 3.223; P=0.001) and psychological stress as a cause of depression (aOR, 4.370; P<0.001); the relationship between chronic physical disease and depression (aOR, 8.984; P<0.001); and other items. Our results suggest that in terms of the biological model of depression, the understanding of registered nurses is greater than that of assistant nurses. Moreover, specific psychiatric education programs for nursing personnel need to be developed in Korea. Our findings can contribute to the development of a general hospital-based model for early detection of depression in patients with chronic medical diseases. PMID- 26130961 TI - Recent Clinical Manifestation and Prognosis of Fungal Endophthalmitis: A 7-Year Experience at a Tertiary Referral Center in Korea. AB - This study analyzed the recent causes, prognosis, and treatment strategies for fungal endophthalmitis. A retrospective review of patients who were diagnosed with fungal endophthalmitis at our center was conducted. The fungal organisms isolated from each patient and the visual prognosis according to the route of infection and treatment method were analyzed. A total of 40 eyes from 30 patients with fungal endophthalmitis were included in this study. Candida species were the most common causative organisms in 35 of 40 eyes. Endogenous and exogenous endophthalmitis were observed in 33 and 7 eyes, respectively. Pre- and post treatment best-corrected visual acuity (BCVA) was not significantly different between endogenous endophthalmitis and exogenous endophthalmitis. The 40 eyes were treated using the following modalities: intravitreal antifungal agent injection with intravenous antifungal agent (16 eyes), vitrectomy with intravenous antifungal agent (14 eyes), intravenous antifungal agent alone (9 eyes), and evisceration (1 eye). Post-treatment BCVA only significantly improved after treatment in the vitrectomy group. Candida species were the most common cause of fungal endophthalmitis, irrespective of the route of infection. The visual prognosis of fungal endophthalmitis was generally poor. In conclusion, if the general condition of the patient tolerates a surgical procedure, prompt vitrectomy and intravitreal injection of antifungal agents can improve visual acuity. PMID- 26130962 TI - MRI Findings and Prediction of Time to Progression of Patients with Hepatocellular Carcinoma Treated with Drug-eluting Bead Transcatheter Arterial Chemoembolization. AB - The purpose of this study was to investigate the utility of MRI findings after drug-eluting beads (DEB) - transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma in predicting time to progression (TTP). This study included 48 patients with 60 lesions who underwent liver MRI within 3 months after DEB-TACE. MRI was assessed for arterial enhancement pattern, late washout, arterioportal shunt, signal intensity on T2-weighted image, intratumoral septa, enhancing tissue on subtraction images, and treatment response. Cox-regression analysis was performed to identify independent factors to predict TTP. TTP was calculated using the Kaplan-Meier method with the log-rank test. Per lesion, 30 achieved complete remission, 22 had a partial response, and the remaining 8 lesions displayed stable disease on MRI. Arterial enhancement pattern, washout and enhancing tissue on subtraction images from MRI were associated with viable tumor on the last follow-up computerized tomography. Arterial enhancement, washout and enhancing tissue on subtraction images were significant predictors of TTP, but only enhancing tissue on subtraction images remained a significant predictor of TTP (P=0.018) in the multivariate analysis. TTP was longer in the group without enhancing tissue on subtraction images compared to the group with enhancing tissue (601 days vs. 287 days, P<0.001). Enhancing tissue on subtraction images from MRI after DEB-TACE is predictive for longer TTP. PMID- 26130963 TI - Comparison of Families with and without a Suicide Prevention Plan Following a Suicidal Attempt by a Family Member. AB - The frequency and extent of the existence of a familial suicide prevention plan may differ across cultures. The aim of this work was, therefore, to determine how common it was for families to develop a suicide prevention plan and to compare the main measures used by families with and without such a plan, after an attempt to commit suicide was made by a member of a family living in a rural area of Korea. On the basis of the presence or absence of a familial suicide prevention plan, we compared 50 recruited families that were divided into 2 groups, with Group A (31 families) employing a familial suicide prevention plan after a suicide attempt by a family member, and Group B (19 families) not doing so. The strategy that was employed most frequently to prevent a reoccurrence among both populations was promoting communication among family members, followed by seeking psychological counseling and/or psychiatric treatment. Contrary to our expectation, the economic burden from medical treatment after a suicide attempt did not influence the establishment of a familial suicide prevention plan. It is a pressing social issue that 38% (19 of 50) of families in this study did not employ a familial suicide prevention plan, even after a family member had attempted suicide. Regional suicide prevention centers and/or health authorities should pay particular attention to these patients and their families. PMID- 26130965 TI - Pertussis Prevalence in Korean Adolescents and Adults with Persistent Cough. AB - We investigated the prevalence of pertussis in Korean adolescents and adults with persistent cough. Study population was adolescents (aged 11-20 yr) and adults (>= 21 yr old) who showed persistent cough of 1-8 weeks' duration. Pertussis was diagnosed by culture, polymerase chain reaction (PCR), and serology. A total of 310 subjects participated in this study, and 76 cases (24.5%) met the criteria for laboratory-confirmed pertussis. The majority of the pertussis cases (66/76) were confirmed by serology, while 3 cases (1.0%) were diagnosed with culture, and 10 cases (3.2%) were detected with PCR. Of the 76 subjects diagnosed with pertussis, 20/86 cases were adolescents and 56/224 cases were adults. Neither adolescents nor adults received adolescent-adult booster against pertussis within the previous 5 yr. Pertussis can be a primary cause of persistent cough in Korean adolescents and adults. PMID- 26130964 TI - Antiangiogenic Activity of Acer tegmentosum Maxim Water Extract in Vitro and in Vivo. AB - Angiogenesis, the formation of new blood vessels, is critical for tumor growth and metastasis. Notably, tumors themselves can lead to angiogenesis by inducing vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors. Inhibition of angiogenesis is currently perceived as one of the most promising strategies for the blockage of tumor growth. In this study, we investigated the effects of Acer tegmentosum maxim water extract (ATME) on angiogenesis and its underlying signal mechanism. We studied the antiangiogenic activity of ATME by using human umbilical vein endothelial cells (HUVECs). ATME strongly inhibited VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation, as well as vessel sprouting in a rat aortic ring sprouting assay. Moreover, we found that the p44/42 mitogen activated protein (MAP) kinase signaling pathway is involved in the inhibition of angiogenesis by ATME. Moreover, when we performed the in vivo matrigel plug assay, VEGF-induced angiogenesis was potently reduced when compared to that for the control group. Taken together, these results suggest that ATME exhibits potent antiangiogenic activity in vivo and in vitro and that these effects are regulated by the extracellular regulated kinase (ERK) pathway. PMID- 26130966 TI - Reversal of Hypoglycemia Unawareness with a Single-donor, Marginal Dose Allogeneic Islet Transplantation in Korea: A Case Report. AB - Pancreatic islet transplantation is a physiologically advantageous and minimally invasive procedure for the treatment of type 1 diabetes mellitus. Here, we describe the first reported case of successful allogeneic islet transplantation alone, using single-donor, marginal-dose islets in a Korean patient. A 59-yr-old patient with type 1 diabetes mellitus, who suffered from recurrent severe hypoglycemia, received 4,163 islet equivalents/kg from a single brain-death donor. Isolated islets were infused intraportally without any complications. The immunosuppressive regimen was based on the Edmonton protocol, but the maintenance dosage was reduced because of mucositis and leukopenia. Although insulin independence was not achieved, the patient showed stabilized blood glucose concentration, reduced insulin dosage and reversal of hypoglycemic unawareness, even with marginal dose of islets and reduced immunosuppressant. Islet transplantation may successfully improve endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus. PMID- 26130967 TI - Numerical modeling of bubble dynamics in viscoelastic media with relaxation. AB - Cavitation occurs in a variety of non-Newtonian fluids and viscoelastic materials. The large-amplitude volumetric oscillations of cavitation bubbles give rise to high temperatures and pressures at collapse, as well as induce large and rapid deformation of the surroundings. In this work, we develop a comprehensive numerical framework for spherical bubble dynamics in isotropic media obeying a wide range of viscoelastic constitutive relationships. Our numerical approach solves the compressible Keller-Miksis equation with full thermal effects (inside and outside the bubble) when coupled to a highly generalized constitutive relationship (which allows Newtonian, Kelvin-Voigt, Zener, linear Maxwell, upper convected Maxwell, Jeffreys, Oldroyd-B, Giesekus, and Phan-Thien-Tanner models). For the latter two models, partial differential equations (PDEs) must be solved in the surrounding medium; for the remaining models, we show that the PDEs can be reduced to ordinary differential equations. To solve the general constitutive PDEs, we present a Chebyshev spectral collocation method, which is robust even for violent collapse. Combining this numerical approach with theoretical analysis, we simulate bubble dynamics in various viscoelastic media to determine the impact of relaxation time, a constitutive parameter, on the associated physics. Relaxation time is found to increase bubble growth and permit rebounds driven purely by residual stresses in the surroundings. Different regimes of oscillations occur depending on the relaxation time. PMID- 26130970 TI - From the Editor's Desk: New Leadership and a New Look. PMID- 26130968 TI - The dual PI3K/mTOR inhibitor NVP-BEZ235 inhibits proliferation and induces apoptosis of burkitt lymphoma cells. AB - BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on cell proliferation and apoptosis in Burkitt lymphoma (BL) cells. METHODS: Two human BL cell lines, CA46 and RAJI were used in this study. The proliferation of BL cells was detected by manganese tricarbonyl transfer (MTT) assay. Cell cycle and apoptosis assay were examined by flow cytometric analysis. The phosphorylation levels of AKT (Thr308), AKT (Ser473), and RPS6 were evaluated by western blot analysis. RESULTS: NVP-BEZ235 significantly inhibited the proliferation of BL cells (CA46 and RAJI) and the inhibition effect was time and dose-dependent. Cell cycle analysis indicated that the cells (CA46 and RAJI) were mostly arrested in G1/G0 phase. Cell apoptosis assay showed that the late apoptotic cells were significantly increased after 72 h treatment by 100 nmol/L of NVP-BEZ235. In addition, results also found that NVP BEZ235 reduced the phosphorylation levels of AKT (Thr308), AKT (Ser473), and PRS6 in BL cells (CA46 and RAJI). Moreover, this inhibition effect on phosphorylation was dose-dependent. CONCLUSIONS: NVP-BEZ235 effectively inhibited cell proliferation by G0/G1 cell-cycle arrest and induced apoptosis through deregulating PI3K/Akt/mTOR pathway in BL cells. PMID- 26130971 TI - Letters to the Editor. PMID- 26130972 TI - Bioethics in Practice - The Ethics of Opiate Use and Misuse from a Hospitalist's Perspective. PMID- 26130973 TI - Clinical Images: Postterm Newborn with Lissencephaly Presented with Seizure: Case Report and Review of Literature. PMID- 26130974 TI - The Dilemma of Treating a Doctor-Patient: A Wrestle of Heart Over Mind? PMID- 26130976 TI - Patients' Perspectives of Surgical Safety: Do They Feel Safe? AB - BACKGROUND: Increased focus on reducing patient harm has led to surgical safety initiatives, including time-out, surgical safety checklists, and debriefings. The perception of the lay public of the surgical safety process is largely unknown. METHODS: A 20-question survey focused on perceptions of surgical safety practice was distributed to a random sample of patients following elective operations requiring hospitalization. Responses were measured by a 7-point Likert scale. Qualitative feedback was obtained through nonphysician-moderated sessions. Participation was voluntary and anonymous. RESULTS: Surveys were distributed to 345 patients of whom 102 (29.5%) responded. Overall, patients felt safe as evidenced by scores for the questions "I felt safe the day of my surgery" (6.53 +/- 0.72) and "Mistakes rarely happen during surgery" (5.39 +/- 1.51). Patients undergoing their first surgery and patients with higher income levels were associated with a significant decrease in specific safety perceptions. Qualitative feedback sessions identified the physician-patient relationship as the most important factor positively influencing patient safety perceptions. CONCLUSION: Current surgical safety practice is perceived positively by our patients; however, patients still identify physician-patient interactions, relationships, and trust as the most positive factors influencing their perception of the safety environment. PMID- 26130975 TI - A Double-Blind Randomized Controlled Trial Comparing Epidural Clonidine vs Bupivacaine for Pain Control During and After Lower Abdominal Surgery. AB - BACKGROUND: Alpha-2 adrenergic agonists produce safe and effective analgesia, but most investigations studying the analgesic effect of alpha-2 adrenoceptor agonists postoperatively included previous or concomitant administration of other analgesics. Because clonidine potentiates the effect of these drugs, its own intrinsic analgesic effect has been difficult to establish. This study was designed to compare the intraoperative and postoperative effects of epidural clonidine vs bupivacaine for patients undergoing lower abdominal surgery. METHODS: This randomized controlled trial included 40 patients aged 18-50 who were scheduled for elective lower abdominal surgery. Patients were randomly divided into 2 groups. Group I (n=20) received epidural clonidine; Group II (n=20) received epidural bupivacaine. Intraoperative and postoperative hemodynamics, pain scores, and complications were monitored. RESULTS: Mean pain scores were significantly lower in Group I compared to Group II (1.5 +/- 0.5 compared to 3.4 +/- 1.0, respectively) in the first 12 hours after surgery. Sedation was more prominent in Group I until 9 hours after surgery. Opioid requirements were significantly lower in Group I. Respiratory rate was similar in the 2 groups. Group I had larger decreases from baseline in systolic blood pressure and diastolic blood pressure than Group II. Heart rate in Group I was reduced from baseline, while it was increased in Group II. Less postoperative nausea and vomiting, urinary retention, pruritus, and shivering were observed in Group I. CONCLUSION: Compared to bupivacaine, epidural clonidine provided effective intraoperative and postoperative analgesia in selected patients, resulting in a decreased intravenous pain medication requirement and prolonged duration of analgesia after epidural infusion was discontinued. PMID- 26130977 TI - It Takes Two to Tango: Improving Patient Referrals from the Emergency Department to Inpatient Clinicians. AB - BACKGROUND: The transfer of responsibility for patient care across clinical specialties is a complex process. Published and anecdotal data suggest that referrals often fail to meet the needs of one or both parties and that patient focus can be lost during the process. Little is known about the Australian situation. METHODS: To obtain a more complete understanding of the referral process, including the nature of communication in an Australian context, we conducted semistructured interviews in a convenience sample of 25 volunteers. Two established strategies for analyzing qualitative data were used. RESULTS: All respondents considered the following information essential components of a referral: an account of the patient's current condition, a working diagnosis or problem statement and history of the presenting concern, key test results or tests awaiting results, a potential management plan, and any special characteristics of the patient. Respondents acknowledged implied, if not literal, power to accept or reject an emergency department (ED) referral and said the imbalance of power was reinforced when the ED physician was junior to the inpatient clinician. Respondents also noted that in addition to the predominant organizational culture, an independent culture is associated with specific shifts. Foremost among the nonclinical aspects of a referral considered to be important was the timeliness of the contact made to achieve the transition. Respondents also said the success of a referral depended on the speaking and listening abilities of all parties. The individual's motivation to accept or reject a referral can also have an impact on communication. CONCLUSION: Respondents attributed the difficulty of negotiating the transfer of a patient's care across the ED and inpatient interface to three distinct factors: variations in the clinical information required, the culture of the organization and of the clinical team in which the transaction takes place, and the characteristics of the individuals involved in the process. Improving communication skills has the potential to improve patient outcomes. PMID- 26130978 TI - Clinical Comparative Effectiveness Research Through the Lens of Healthcare Decisionmakers. AB - BACKGROUND: Healthcare expenditures in the United States exceed the healthcare expenditures of other countries, yet relatively unfavorable health outcomes persist. Despite the emergence of numerous evidence-based interventions, wide variations in clinical care have caused disparities in quality of care and cost. Comparative effectiveness and cost effectiveness research may better guide healthcare decisionmakers in determining which interventions work best, for which populations, under which conditions, and at what cost. METHODS: This article reviews national health policies that promote comparative effectiveness research (CER), healthcare decisionmaker roles in CER, methodological approaches to CER, and future implications of CER. RESULTS: This article provides a brief summary of CER health policy up to the Patient Protection and Affordable Care Act and its establishment of the Patient-Centered Outcomes Research Institute (PCORI). Through PCORI, participatory methods for engaging healthcare decisionmakers in the entire CER process have gained momentum as a strategy for improving the relevance of research and expediting the translation of research into practice. Well-designed, methodologically rigorous observational studies and randomized trials conducted in real-world settings have the potential to improve the quality, generalizability, and transferability of study findings. CONCLUSION: Learning health systems and practice-based research networks provide the infrastructure for advancing CER methods, generating local solutions to high quality cost-effective care, and transitioning research into implementation and dissemination science-all of which will ultimately guide health policy on clinical care, payment for care, and population health. PMID- 26130979 TI - Stellate Ganglion Block for the Treatment of Hot Flashes in Patients with Breast Cancer: A Literature Review. AB - BACKGROUND: Currently, hormone replacement therapy (HRT) is the only US Food and Drug Administration-approved treatment for hot flashes, resulting in clinical improvement in 80%-90% of symptomatic women. However, HRT is not recommended for patients with breast cancer. Current data regarding the use of stellate ganglion block (SGB) for the treatment of vasomotor symptoms in symptomatic women with a diagnosis of breast cancer are promising. METHODS: A PubMed search for recent articles on the effects of SGB for the treatment of hot flashes in patients with breast cancer identified 11 articles published between 2005-2014. RESULTS: Five articles described the physiology of hot flashes and the hypothesis of why SGB would be a treatment option, and 6 were clinical articles. CONCLUSION: The available results of SGB efficacy are promising but demonstrate significant variability. A large prospective randomized controlled trial is required to determine the exact success of SGB on hot flashes and quality of life in breast cancer survivors. PMID- 26130980 TI - Rhabdomyolysis After Cooked Seafood Consumption (Haff Disease) in the United States vs China. AB - BACKGROUND: Haff disease is a syndrome of myalgia and rhabdomyolysis that occurs after eating cooked seafood. METHODS: For this descriptive analytical article, a literature search identified the scientific articles on Haff disease and/or rhabdomyolysis after eating cooked seafood in the United States and China. Analysis of those articles focused on identifying the seafood vectors of Haff disease, describing the most commonly recurring clinical and laboratory manifestations of Haff disease, and comparing the Haff disease toxidrome with other similar seafood-borne toxidromes. Statistically significant differences were determined using unpaired t tests and Fisher exact tests. RESULTS: Twenty nine confirmed cases of Haff disease were identified in the United States, and 60 cases were identified in China during 1984-2014. Most of the US cases followed consumption of buffalo fish, and most of the Chinese cases followed consumption of freshwater pomfret. However, Haff disease also followed consumption of the same species of boiled crayfish (Procambarus clarkii) in the United States (n=9) and China (n=6). US patients with crayfish-transmitted Haff disease reported significantly more nausea with and without vomiting, chest pain, body and back pain, dyspnea, and diaphoresis than the Chinese patients and were more frequently misdiagnosed as having myocardial infarctions. CONCLUSION: The bioaccumulation of a new, heat-stable freshwater and/or brackish/saltwater algal toxin, similar to palytoxin but primarily myotoxic and not neurotoxic, is suspected of causing Haff disease. At present, only the rapid identification of the seafood vectors of Haff disease will limit disease outbreaks and prevent further cases. PMID- 26130981 TI - Recurrent Bronchogenic Cyst After Surgical Resection. AB - BACKGROUND: Bronchogenic cysts are rare congenital anomalies that are often solitary and rarely multiple. Most bronchogenic cysts are asymptomatic, and symptoms when present are usually the result of compression by the cyst on the surrounding structures. CASE REPORT: We report a case of recurrent bronchogenic cyst following a partial resection treated with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). CONCLUSION: EBUS-TBNA can provide instant decompression of the cyst and relieves the pressure on the surrounding structures. PMID- 26130982 TI - The Will to Live: Preservation of a Forearm Loop Arteriovenous Graft via Development of Median Cubital Venous Collateral Circulation. AB - BACKGROUND: Forearm loop arteriovenous grafts most commonly fail because of stenosis, with thrombosis at the venous anastomosis. Treatment begins with identification of the stenotic lesion causing thrombosis, followed by either a percutaneous method using thrombolytic agents with possible balloon angioplasty and mechanical evacuation or surgical thrombectomy. CASE REPORT: We present a case of thrombosis in a forearm loop graft with successful percutaneous thrombectomy. Preservation of this access site was only possible because of an unusual finding of collateral circulation, with the median cubital vein acting as a conduit to the basilic vein. CONCLUSION: The choice of surgical vs percutaneous methods for treating a thrombosed graft remains controversial. Yet the success rates of pharmacologic thrombolysis and the percutaneous approach are comparable to those of surgical thrombectomy. Our case of successful percutaneous thrombectomy illustrates the value of preserving the median cubital vein whenever possible in the placement of forearm arteriovenous grafts. PMID- 26130983 TI - A Case of Severe Anaphylactic Reaction Secondary to Isosulfan Blue Dye Injection. AB - BACKGROUND: Allergic reactions including anaphylaxis resulting from isosulfan blue dye are rare but warrant a thorough review given that lymph node mapping has become an increasingly common procedure, putting more patients at risk. CASE REPORT: Our patient was an 82-year-old female who underwent elective excision of a right forearm melanoma and right axillary sentinel lymph node mapping and suffered an anaphylactic reaction approximately 15 minutes after injection of isosulfan blue dye. The procedure was aborted. She was intubated; diphenhydramine and dexamethasone were administered; her blood pressure was stabilized with phenylephrine, epinephrine, and intravenous fluids; and she was transferred to the intensive care unit. She was extubated on postoperative day 1 and discharged home on postoperative day 2. CONCLUSION: Sentinel lymph node biopsy is the standard of care for staging several cancers, and isosulfan blue is the dye most commonly used for this procedure. Reactions to the dye occur in some patients; however, we recommend the continued use of isosulfan blue dye for lymph node mapping given the low incidence of adverse effects, with no reported mortalities. Physicians should be prepared for the potential risk of anaphylactic shock. PMID- 26130984 TI - Rituximab-Induced Acute ST Elevation Myocardial Infarction. AB - BACKGROUND: Rituximab has rarely been associated with acute coronary syndrome (ACS). We report the case of a patient in whom rituximab, a monoclonal antibody used to treat lymphomas of B-cell origin, induced ST elevation myocardial infarction. CASE REPORT: A 46-year-old male patient diagnosed with stage II non Hodgkin lymphoma presented to the emergency department with acute crushing, substernal chest pain that radiated to his back 1 day after a chemotherapy infusion with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. An electrocardiogram revealed normal sinus rhythm with ST elevations in the inferior leads. The patient underwent primary percutaneous coronary intervention (PCI) of his right coronary artery and first diagonal artery with placement of drug-eluting stents. He did well postprocedure and resumed therapy with rituximab under close monitoring by the cardiology and oncology departments without any further cardiac events. CONCLUSION: In patients with ACS because of chemotherapy, complete revascularization during PCI should be considered. PMID- 26130985 TI - Extrusion of a NeuroTube: A Case Report. AB - BACKGROUND: Peripheral nerve injury is a common result of trauma. In cases of nerve gap, treatment may involve placement of a nerve conduit. This case involves a polyglycolic acid nerve conduit tube that was extruded through soft tissue. To our knowledge, this reactive process has only been previously documented in one article. This complication is not commonly known among hand surgeons, hence our interest in documenting it. CASE REPORT: We present the case of a 33-year-old male who injured his right nondominant thumb in a workplace saw accident. His complex wound involved the radial digital nerve, and the nerve was repaired using a polyglycolic acid nerve conduit. By postoperative week 4, part of the nerve conduit was extruding through the wound. No signs of infection were noted, and the remainder of his wounds had healed. The patient declined a nerve graft, so his wound was debrided with no further attempts at nerve repair. The wound healed uneventfully, and the patient returned to full duty without restrictions. CONCLUSION: We believe this is the first documented case of extrusion of a nerve conduit through healthy soft tissue. Recent advancements in nerve allografts and conduits hold promise but are not yet in widespread use. We recommend the use of a collagen conduit to avoid extrusion of polyglycolic acid-based materials. PMID- 26130986 TI - Effective Management of Trigeminal Neuralgia by Neurostimulation. AB - BACKGROUND: Treatment of trigeminal neuralgia can be challenging for many physicians; patients who do not respond to conventional treatments and traditional surgical approaches often continue to suffer with pain. The peripheral nerve stimulator (PNS) has been used to treat many chronic pain conditions, but few reports exist about its use to treat trigeminal neuralgia. CASE REPORT: We present the case of a patient with trigeminal neuralgia resistant to conventional techniques of pain management. Conservative pain management was attempted but was ineffective. As a result, a PNS was placed with minimally invasive surgery. Pain scores were recorded before and after the procedure, and the patient reported complete resolution of her pain. CONCLUSION: PNS implantation can be a safe and effective method to treat trigeminal neuralgia. More research is needed to define its mechanism of action. PMID- 26130987 TI - Antemortem Diagnosis of Likely Giant Cell Carcinoma of the Lung by Pleural Fluid Cytology Evaluation. AB - BACKGROUND: Sarcomatoid carcinomas (SCs) are poorly differentiated non-small cell lung carcinomas containing components of either sarcomatoid differentiation or true sarcoma. SCs have a poor prognosis; some studies suggest a 6-month survival rate <27%. CASE REPORT: We present a case of the rare entity of SC, likely giant cell carcinoma, that is unique because our patient was older than the mean age at presentation, was female, and had a central lesion. CONCLUSION: Clinicians need to be aware of the histologic entities of SCs of the lung because of the aggressive nature of these lesions and because of the need for further studies to determine possible treatment regimens. PMID- 26130988 TI - Benign Sacral Metastatic Meningioma: A Rare Entity. AB - BACKGROUND: Meningiomas are common intracranial tumors with a low metastatic rate. Those that do metastasize often show histopathologic signs of malignancy. In rare cases, the primary and secondary tumors are histologically benign. CASE REPORT: We report the case of a 57-year-old female with a histologically benign intracranial meningioma that metastasized to the sacrum. The patient had a long history of intracranial meningioma with multiple recurrences. At each recurrence, histopathologic examination of the resected tumor showed no signs of malignancy. The sacral meningioma was biopsied and found to be histologically benign. The patient was treated with radiotherapy (54 Gy in 30 fractions), and her symptoms resolved. Six months later, the patient developed left leg weakness. Magnetic resonance imaging showed growth of her intracranial mass for which she underwent a craniotomy for tumor resection. Pathologic evaluation showed evidence of benign meningioma without atypical features. She recovered well from this procedure and returned to her baseline in several weeks. CONCLUSION: After treatment, the patient had no signs of radiographic progression in either location. PMID- 26130989 TI - An Unusual Cause of Dysphagia: A Large Expectorated Arteriovenous Malformation. AB - BACKGROUND: Vascular malformations are generally detected in childhood or adolescence with first presentations in adulthood being rare. CASE REPORT: We report the case of a 52-year-old female with threatened compromise of her airway after expectorating a massive arteriovenous malformation anchored at the supraglottis. The only preceding symptom was dysphagia. The lesion was resected, the patient had a quick recovery, and she has shown no evidence of recurrence. CONCLUSION: Although uncommon, vascular malformations of the supraglottis or hypopharynx should be considered in the differential diagnosis of a patient presenting with dysphagia because of the potential to cause disastrous airway compromise. Although a lesion presenting acutely mandates a definitive airway plan, when clinically possible, computed tomography scan and indirect laryngoscopy can provide useful information for the airway and operative teams. PMID- 26130991 TI - Inflammatory Bowel Disease in Asia: The Challenges and Opportunities. PMID- 26130992 TI - Is Long-Term Therapy With Thiopurines Effective for Maintaining Remission in Patients With Moderate-To-Severe Ulcerative Colitis? PMID- 26130990 TI - Recent Publications by Ochsner Authors. PMID- 26130994 TI - Optimization of Inflammatory Bowel Disease Cohort Studies in Asia. AB - With the incidence of inflammatory bowel disease (IBD) increasing rapidly in many Asian countries, including Hong Kong, it is important that patient characteristics are better understood. For example, are the phenotypes, behaviors, complications, and even treatment responses found in Asian patients similar to those of their Western counterparts? To formally address these questions, a properly designed local cohort study is needed. Whilst IBD is still relatively uncommon in Asia, the establishment of a local IBD registry will significantly contribute to the answering of these questions. The Hong Kong IBD registry was established to fill the gap in the understanding of IBD patients, and to foster research into IBD in Hong Kong. The Hong Kong IBD registry is a territory-wide registry that includes all public hospitals in Hong Kong. We included all IBD patients who were currently receiving medical care at these hospitals. With the help of the central computer medical record system of the Hospital Authority of Hong Kong, all clinical events, medications usage, endoscopy records, and laboratory results of patients in the registry were captured. Apart from data collection, the registry is also establishing a bio specimen bank of blood and stool samples of IBD patients for future research. The IBD registry is a very useful platform for population-based studies on IBD in Asia. PMID- 26130993 TI - Use of Thiopurines in Inflammatory Bowel Disease: A Consensus Statement by the Korean Association for the Study of Intestinal Diseases (KASID). AB - BACKGROUND/AIMS: For decades, thiopurines have been the mainstay of inflammatory bowel disease (IBD) treatment and will play an important role in the future. However, complex metabolism and various side effects limit the use of these potent drugs in clinical practice. The Korean Association for the Study of Intestinal Diseases developed a set of consensus statements with the aim of guiding clinicians on the appropriate use of thiopurines in the management of IBD. METHODS: Sixteen statements were initially drafted by five committee members. The quality of evidence and classification of recommendation were assessed according to the Grading of Recommendations Assessment, Development and Evaluation system. The statements were then circulated to IBD experts in Korea for review, feedback, and then finalized and accepted by voting at the consensus meeting. RESULTS: The consensus statements comprised four parts: (1) pre treatment evaluation and management strategy, including value of thiopurine S methyltransferase screening, dosing schedule, and novel biomarkers for predicting thiopurine-induced leukopenia; (2) treatment with thiopurines with regards to optimal duration of thiopurine treatment and long-term outcomes of combination therapy with anti-tumor necrosis factors; (3) safety of thiopurines, especially during pregnancy and lactation; and (4) monitoring side effects or efficacy of therapy using biomarkers. CONCLUSIONS: Thiopurines are an effective treatment option for patients with IBD. Management decisions should be individualized according to the risk of relapse and adverse events. PMID- 26130995 TI - Inflammatory Bowel Disease Cohort Studies in Korea: Present and Future. AB - Inflammatory bowel disease (IBD) is defined as a chronic and relapsing inflammatory disorder of the intestine. Intestinal inflammation in IBD has been proposed to be attributable to the interplay between microbial, genetic, environmental, and immunological factors. The incidence and prevalence rates of IBD are rapidly increasing apparently in other parts of the world, with dramatic increases especially in East Asia. Generally, cohort studies are useful for estimating the incidence, prevalence, natural course, prognosis, and risk factors of diseases. In particular, cohort studies performed in Western countries have well described the prevalence, risk factors, and natural course of IBD and investigated its genetic pathophysiology. However, the outcomes of IBD cohort studies performed in Korea are not as persuasive as those of Western studies because of the relatively low prevalence of IBD and short follow-up periods of the cohorts in Korea. Despite this critical limitation, members of the Korean Association for the Study of Intestinal Diseases have demonstrated outstanding results. Some unique features of IBD patients in Korea are well demonstrated, such as thiopurine-induced leukopenia or risks of opportunistic tuberculosis infection in patients receiving tumor necrosis factor-alpha inhibitors. In this review, the present authors summarized the key points of the results of the cohort studies performed in Korea and explored future perspectives. PMID- 26130996 TI - Tacrolimus for the Treatment of Ulcerative Colitis. AB - Tacrolimus is a calcineurin inhibitor used for the treatment of corticosteroid refractory ulcerative colitis (UC). Two randomized controlled trials and a number of retrospective studies have assessed the therapeutic effect of tacrolimus in UC patients. These studies showed that tacrolimus has excellent short-term efficacy in corticosteroid-refractory patients, with the rates of clinical response ranging from 61% to 96%. However, the long-term prognosis of patients treated with tacrolimus is disappointing, and almost 50% of patients eventually underwent colectomy in long-term follow-up. Tacrolimus can achieve mucosal healing in 40 50% of patients, and this is associated with a favorable long-term prognosis. Anti-tumor necrosis factor (TNF)-alpha antibodies are another therapeutic option in corticosteroid-refractory patients. A prospective head-to-head comparative study of tacrolimus and infliximab is currently being performed to determine which treatment is more effective in corticosteroid-refractory patients. Several retrospective studies have demonstrated that switching between tacrolimus and anti-TNF-alpha antibody therapy was effective in patients who were refractory to one of the treatments. Most adverse events of tacrolimus are mild; however, opportunistic infections, especially pneumocystis pneumonia, are the most important adverse events, and these should be carefully considered during treatment. Several issues on tacrolimus treatment in UC patients remain unsolved (e.g., use of tacrolimus as remission maintenance therapy). Further controlled studies are needed to optimize the use of tacrolimus for the treatment of UC. PMID- 26130997 TI - 'Lemonade Legs': Why do Some Patients Get Profound Hypomagnesaemia on Proton-Pump Inhibitors? AB - Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis. PMID- 26130998 TI - Balsalazide Potentiates Parthenolide-Mediated Inhibition of Nuclear Factor-kappaB Signaling in HCT116 Human Colorectal Cancer Cells. AB - BACKGROUND/AIMS: Balsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. Balsalazide can reduce inflammatory responses via several mechanisms, including inhibition of nuclear factor-kappaB (NF-kappaB) activity. Parthenolide (PT) inhibits NF-kappaB and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-kappaB in a representative human colorectal carcinoma cell line, HCT116. METHODS: We counted cells and conducted annexin-V assays and cell cycle analysis to measure apoptotic cell death. Western blotting was used investigate the levels of proteins involved in apoptosis. RESULTS: PT and balsalazide produced synergistic anti-proliferative effects and induced apoptotic cell death. The combination of balsalazide and PT markedly suppressed nuclear translocation of the NF-kappaB p65 subunit and the phosphorylation of inhibitor of NF-kappaB. Moreover, PT and balsalazide dramatically enhanced NF kappaB p65 phosphorylation. Apoptosis, through the mitochondrial pathway, was confirmed by detecting effects on Bcl-2 family members, cytochrome c release, and activation of caspase-3 and -8. CONCLUSIONS: Combination treatment with PT and balsalazide may offer an effective strategy for the induction of apoptosis in HCT116 cells. PMID- 26130999 TI - Polymorphisms in PRKCDBP, a Transcriptional Target of TNF-alpha, Are Associated With Inflammatory Bowel Disease in Korean. AB - BACKGROUND/AIMS: Emerging data indicate that polymorphic sequence variations in the tumor necrosis factor alpha (TNF-alpha) gene may affect its production, and be associated with the risk of inflammatory bowel disease (IBD). PRKCDBP is a putative tumor suppressor gene and a transcriptional target of TNF-alpha. The aim of this case-control study is to explore the possible association of single nucleotide polymorphisms (SNPs) in PRKCDBP with the development of IBD in Koreans. METHODS: Genotyping analysis of four SNPs of PRKCDBP [rs35301211 (G210A), rs11544766 (G237C), rs12294600 (C797T), and rs1051992 (T507C)] was performed on 170 ulcerative colitis (UC),131 Crohn's disease (CD) patients, and 100 unrelated healthy controls using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: Heterozygous configuration of three SNPs (G210A, G237C, and C797T) was very rare in both patients and healthy controls. However, allele frequencies of the T507C SNP showed a significant difference between UC patients and controls (P=0.037). The CC genotype of the T507C SNP was identified in 46.6% (61 of 131) of CD and 49.4% (84 of 170) of UC patients, but only in 33.0% (33 of 100) of healthy controls. Furthermore, CC homozygosity was more prevalent than TC heterozygosity in both CD and UC patients versus controls (P=0.016; gender-adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.16-4.04 and P=0.009; aOR, 2.09; 95% CI, 1.193.64; respectively). CONCLUSIONS: Our results suggest that the T507C SNP in PRKCDBP, a TNF-alpha-inducible gene, might be associated with susceptibility to IBD (particularly UC) development in Koreans. PMID- 26131000 TI - Efficacy and Safety of Long-Term Thiopurine Maintenance Treatment in Japanese Patients With Ulcerative Colitis. AB - BACKGROUND/AIMS: The long-term clinical outcomes of patients with bio-naive ulcerative colitis (UC) who maintain remission with thiopurine are unclear. The aim of this study was to assess the long-term efficacy and safety of maintenance treatment with thiopurine in UC patients. METHODS: This was a retrospective observational cohort analysis conducted at a single center. Between December 1998 and August 2013, 59 of 87 patients with bio-naive UC who achieved remission after induction with treatments other than biologics were enrolled. Remission maintenance with thiopurine was defined as no concomitant treatment needed other than 5-aminosalicylate without relapse. We assessed the remission-maintenance rate, mucosal healing rate, colectomy-free rate, and treatment safety in UC patients who received thiopurine as maintenance treatment. RESULTS: The 84-month cumulative remission-maintenance and colectomy-free survival rates in the UC patients who were receiving maintenance treatment with thiopurine and 5 aminosalicylate were 43.9% and 88.0%, respectively. Of the 38 patients who underwent colonoscopy during thiopurine maintenance treatment, 23 (60.5%) achieved mucosal healing. Of the 59 patients who achieved clinical remission with thiopurine, 6 patients (10.2%) discontinued the thiopurine therapy because of adverse events. CONCLUSIONS: Our study demonstrates the long-term efficacy and safety of thiopurine treatment in patients with bio-naive UC. PMID- 26131001 TI - Conventional Versus Biological Therapy for Prevention of Postoperative Endoscopic Recurrence in Patients With Crohn's Disease: an International, Multicenter, and Observational Study. AB - BACKGROUND/AIMS: Postoperative endoscopic recurrence (PER) occurs in nearly 80% of patients 1 year after ileocecal resection in patients with Crohn's disease (CD). Biological agents were more effective in reducing the rates of PER in comparison with conventional therapy, in prospective trials. The aim of this study was to compare the PER rates of biological versus conventional therapy after ileocecal resections in patients with CD in real-world practice. METHODS: The MULTIPER (Multicenter International Postoperative Endoscopic Recurrence) database is a retrospective analysis of PER rates in CD patients after ileocecal resection, from 7 referral centers in 3 different countries. All consecutive patients who underwent ileocecal resections between 2008 and 2012 and in whom colonoscopies had been performed up to 12 months after surgery, were included. Recurrence was defined as Rutgeerts' score >=i2. The patients were allocated to either biological or conventional therapy after surgery, and PER rates were compared between the groups. RESULTS: Initially, 231 patients were evaluated, and 63 were excluded. Of the 168 patients in the database, 96 received anti-tumor necrosis factor agents and 72 were treated with conventional therapy after resection. The groups were comparable regarding age, gender, and perianal disease. There was longer disease duration, more previous resections, and more open surgical procedures in patients on biologicals postoperatively. PER was identified in 25/96 (26%) patients on biological therapy and in 24/72 (33.3%) patients on conventional therapy (P=0.310). CONCLUSIONS: In this retrospective observational analysis from an international database, no difference was observed between biological and conventional therapy in preventing PER after ileocecal resections in CD patients. PMID- 26131002 TI - Efficacy of Thiopurines in Biologic-Naive Japanese Patients With Crohn's Disease: A Single-Center Experience. AB - BACKGROUND/AIMS: Early use of biologics in patients with Crohn's disease (CD) improves quality of life. However, the effects of the early use of immunomodulators on long-term outcomes remain unclear. This study aimed to evaluate the effects of immunomodulators in patients with CD. METHODS: Between January 2004 and December 2011, 47 biologic-naive CD patients treated with thiopurines alone for remission maintenance were analyzed. The patients were classified into 2 groups depending on the presence or absence of digestive complications. We evaluated the efficacy of and predictive factors for thiopurine use for remission maintenance. RESULTS: The cumulative relapse rates at 24 and 60 months were 13.7% and 35.4%, respectively. Regarding patient characteristics, there was a significant difference in patient history of surgery between the non relapse and relapse groups (P=0.021). The cumulative relapse rate was lower in patients without a history of surgery than in those with such a history (27.2% and 52.9% at 60.0 months, respectively). Multivariate analysis suggested that the prevalence of stricturing and penetrating complications is an independent factor for relapse. The cumulative relapse rate in patients without a history of surgery was significantly lower in the non-stricturing and non-penetrating group than in the stricturing and penetrating group (11.8% at 85.0 months vs. 58.5% at 69.0 months; P=0.036). CONCLUSIONS: Thiopurine use might be beneficial for the long term maintenance of remission in biologic-naive Crohn's disease patients without digestive complications and a history of surgery. PMID- 26131003 TI - Institutional Board Review for Clinical Investigations on Inflammatory Bowel Diseases: A Single-Center Study. AB - BACKGROUND/AIMS: The growing volume and the diversity of clinical research has led to related laws and regulations as well as the Institutional Review Board (IRB) approval process becoming more stringent. To conduct clinical research efficiently and while following regulations, information about the IRB approval process and feedback is important for investigators. This has yet to be studied. METHODS: We included 381 gastrointestinal disease research proposals (79 with inflammatory bowel disease [IBD], and 302 with non-IBD) reviewed by the IRB of Severance Hospital between January 2009 and December 2013. We retrospectively analyzed research characteristics including research risk levels, results of initial reviews, frequencies of continuing review, numbers of IRB comments, frequencies of IRB comments, and durations from submission to approval. RESULTS: Investigators' decisions on risk level were higher in the IBD group than in the non-IBD group (P<0.05). Results of initial reviews, frequencies of continuing reviews, the numbers of IRB review comments, and durations from submission to approval were not different between the two groups, but IRB decisions on risk level were higher in the IBD group (P<0.05). In subgroup analysis, the number of IRB comments from initial review on informed consent forms and procedures as well were quest of more information were significantly higher in the IBD group than in the non-IBD group (P<0.001 and 0.01, respectively). CONCLUSIONS: In Korea, rare diseases such as IBD require more information for the IRB process due to their distinct characteristics. IBD researchers should develop research protocols more carefully and make their research as subject-friendly as possible. PMID- 26131004 TI - Intestinal Pseudo-Obstruction as an Initial Manifestation of Systemic Lupus Erythematosus. AB - Intestinal pseudo-obstruction (IPO) is an uncommon, severe complication that occurs in a small subgroup of patients with systemic lupus erythematosus (SLE). To our knowledge, approximately 30 cases of IPO in SLE have been reported in the literature. Moreover, IPO is rare as an initial manifestation of SLE. We report a case of a 43-year-old woman with SLE who initially presented with IPO. PMID- 26131005 TI - Familial Mediterranean Fever With Complete Symptomatic Remission During Pregnancy. AB - Familial Mediterranean fever (FMF) is an inherited autosomal recessive disorder, ethnically restricted and commonly found among populations surrounding the Mediterranean Sea. FMF is the most prevalent autoinflammatory disease; is characterized by recurrent, self-limited episodes of fever with serositis; and is caused by Mediterranean fever gene (MEFV) mutations on chromosome 16. We describe a case of adult-onset FMF with complete symptomatic remission during pregnancy, without the use of colchicine. A 25-year-old woman had presented with periodic fever, abdominal pain, and vomiting since she was 21. Her abdominal computed tomography scan showed intestinal nonrotation. She underwent exploratory laparotomy and appendectomy for her symptoms 1 year prior. She had a symptom-free pregnancy period, but abdominal pain and fever recurred after delivery. Mutation analysis of the MEFV gene revealed two point mutations (p.Leu110Pro and p.Glu148Gln). We report an adult female patient with FMF in Korea with complete symptomatic remission during pregnancy. PMID- 26131006 TI - A Patient With Abdominal Pain and Fever. PMID- 26131007 TI - Granulocyte colony-stimulating factor and reproductive medicine: A review. AB - BACKGROUND: Recently, the use of granulocyte colony-stimulating factor (G-CSF) has been proposed to improve pregnancy outcomes in reproductive medicine. OBJECTIVE: A systematic review of the current use of G-CSF in patients who have difficulty conceiving and maintaining pregnancy was performed. MATERIALS AND METHODS: Two electronic databases (PubMed/ Medline and Scopus) were searched. Study selection, data extraction and quality assessment were performed in duplicate. The subject codes used were granulocyte colony-stimulating factor, G CSF, recurrent miscarriage, IVF failure, and endometrium. RESULTS: The search of electronic databases resulted in 215 citations (PubMed/ Medline: 139 and Scopus: 76), of which 38 were present in both databases. Of the remaining 177 publications, seven studies were included in the present review. CONCLUSION: Treatment with G-CSF is a novel proposal for immune therapy in patients with recurrent miscarriage and implantation failure following cycles of IVF. However, a larger number of well-designed studies are required for this treatment to be established. PMID- 26131009 TI - The association between single nucleotide polymorphism in interleukin-27 gene and recurrent pregnancy loss in Iranian women. AB - BACKGROUND: Recurrent pregnancy loss (RPL) has been defined as two or more miscarriages before 20(th) week of gestation. It seems that IL-27 may reduce inflammatory responses and affect the survival of the embryo during human pregnancy. IL-27 polymorphisms may influence RPL by altering the levels or the activity of gene product. OBJECTIVE: We studied for the first time the association of IL-27 -964 A>G single nucleotide polymorphism (SNP) with RPL in Iranian women. MATERIALS AND METHODS: A case-controlled study was performed on two groups consisting of 150 healthy women with at least one delivery (control group) and 150 women with two or more primary RPLs history (RPL group). The -964 A>G SNP in IL-27 gene was determined by PCR-RFLP technique. Genotype and allele frequencies were compared using (2) tests between two groups. RESULTS: There was no difference between the two groups regarding age of women (29+/-4.4 [control] vs. 30.84+/-5.2 years [case]). In the RPL group, the genotype frequencies of -964 A>G polymorphism were AG (49.3%), AA (40%), and GG (10.7%), and in the control group, they were AG (43.3%), AA (48.7%), and GG (8%). There was no significant difference between the genotypes of AA, AG, and GG in two groups (p=0.23). As the frequency of allele A was 64.7% in the RPL group and 70.3% in the control group, the difference in frequency of allele A in -964 A>G between two groups was not significant (p=0.19). CONCLUSION: Our findings indicate that SNP of -964 A>G in IL-27 gene is not a risk factor for RPL in Iranian women. PMID- 26131008 TI - Comparison of serum 25-hydroxy vitamin D levels between mothers with small for gestational age and appropriate for gestational age newborns in Kerman. AB - BACKGROUND: Vitamin D deficiency during pregnancy is associated with some adverse pregnancy outcomes but its relationship with fetal growth is unknown. OBJECTIVE: We compared the 25-hydroxy vitamin D levels between mothers and their small for gestational age (SGA) newborns with mothers and their appropriate for gestational age (AGA) newborns. MATERIALS AND METHODS: The study population included pregnant women that referred to Afzalipour Hospital in Kerman from 2012 to 2013. The case and control group consisted of 40 pregnant mothers with SGA and AGA newborns, respectively. The maternal and infants 25-hydroxy vitamin D levels were measured in the two groups. RESULTS: 25-hydroxy vitamin D deficiency (<20 ng/ml) was statistically higher in women with SGA newborns in comparison to women with AGA newborns (p=0.003).Vitamin D deficiency was higher among the SGA newborns in comparison to AGA newborns (25% vs. 17.5%), although this finding was not statistically meaningful (p=0.379). The relationship of vitamin D deficiency levels between mothers and infants in both the SGA group and the AGA group was significant. CONCLUSION: Our study reveals a high prevalence of vitamin D deficiency in women with SGA infants in comparison to women with AGA children. In addition, maternal vitamin D deficiency is associated with its deficiency in newborns. PMID- 26131010 TI - SULF 1 gene polymorphism, rs6990375 is in significant association with fetus failure in IVF technique. AB - BACKGROUND: Sulfatase 1 (SULF1) function is to remove the 6-O-sulphate group from heparan sulfate. This action changes the binding sites of extracellular growth factors. SULF1 expression has been reported to be changed in angiogenesis. We hypothesized that single nucleotide polymorphisms (SNPs) of SULF1 would impact clinicopathologic characteristics. OBJECTIVE: Study of SULF1 gene polymorphism with fetus failure in in vitro fertilization (IVF) technique. MATERIALS AND METHODS: We studied one common (minor allele frequency >0.05) regulatory SNP, rs6990375, with polymerase chain reaction and restriction fragment length polymorphism method, in 53 infertile women with fetus failure in IVF technique and 53 women with at least one healthy child as controls. RESULTS: We found that rs6990375 is significantly associated with an early failure in IVF and frequency of G allele is high in women with fetus failure in IVF technique (p<0.001). CONCLUSION: These findings suggest that SULF1genetic variations may play a role in IVF technique fetus failure. Further studies with large sample sizes on SULF1 SNPs may be useful in support of this claim. PMID- 26131011 TI - Lack of association of DRD3 and CNR1 polymorphisms with premenstrual dysphoric disorders. AB - BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized with physical and affective symptoms during the luteal phase of susceptible women. OBJECTIVE: The aim of this study was to investigate the association of Dopamine D3 receptor (DRD3) polymorphism, and Cannabinoid receptor Type 1 (CNR1) polymorphism with PMDD. MATERIALS AND METHODS: Fifty one participants with documented PMDD according to the DSM IV criteria and 51 healthy controls were included in this cross sectional study. Symptom severity was measured with daily self-rating, monthly premenstrual assessment forms and psychiatric interviews. The genotyping of DRD3 receptor and Cannabinoid type 1 receptors were performed using Taqmanfluorogenic assay method. RESULTS: Distribution of DRD3 and CNR1 polymorphism was not different between patients and controls. CONCLUSION: These findings do not support a major role of DRD3, and CNR1 polymorphisms in contributing to susceptibility to premenstrual dysphoric disorder. PMID- 26131012 TI - Anti-mullerian hormon level and polycystic ovarian syndrome diagnosis. AB - BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrinopathy that accompanied with long term complications. The early diagnosis of this syndrome can prevent it. OBJECTIVE: The aim was to determine the role of anti-mullerian hormon (AMH) in PCOS diagnosis and to find cut off level of it. MATERIALS AND METHODS: In this cross sectional study, 117 women between 20-40 years old were participated in two groups: 60 PCOS women (based on Rotterdam criteria consensus) as the case group and 57 normal ovulatory women as the control group. In day 2-4 of cycle, transvaginal sonography was performed and serum hormonal level of AMH, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone, fasting blood sugar (FBS), thyroid stimulating hormone (TSH), and prolactin (PRL) were measured in all of participants. For all of them score of hirsutism (base on Freeman-Galloway scoring) was determined. RESULTS: There were statistically significant in irregular pattern of menstruation, AMH and FSH level, and presence of hirsutism between two groups. But regarding mean of age, body mass index, plasma level of PRL, TSH, LH, Testosterone, FBS, and E2 differences were not significant. Construction by ROC curve present 3.15 ng/ml as AMH cut off with 70.37% sensitivity and 77.36% specificity in order to PCOS diagnosis. CONCLUSION: AMH with cut off level of 3.15 ng/ml with sensitivity 70.37% and specificity 77.36% could use for early diagnosis of PCOS patients. PMID- 26131013 TI - Assessment of the relationship of basal serum anti-mullerian hormone levels with oocyte quality and pregnancy outcomes in patients undergoing ICSI. AB - BACKGROUND: Anti-Mullerian hormone (AMH) is constantly secreted during menstrual cycles and may offer several advantages over traditional biomarkers of ovarian reserve. OBJECTIVE: To assess the relationship of anti-Mullerian hormone (AMH) values, which are used to evaluate ovary reserves, with oocyte and embryo quality and with ART outcomes in patients undergoing intra-cytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: This cross sectional study was performed using 50 women undergoing ICSI in IVF center of Zeynep Kamil Women's and Children's Hospital, Istanbul, Turkey. All patients received the long protocol. Follicle stimulating hormone, luteinizing hormone, estradiol, and AMH levels were measured and antral follicle counts were obtained on the 3(rd) day of menstruation. A cut off value based on the number of oocytes was determined for AMH, and women were evaluated after being divided into two groups as bad responders and good responders, according to their AMH levels. RESULTS: Twelve (27.3%) women were in bad responders group and 32 (72.7%) women were in good responders group. AMH measurements were statistically significantly different between the two groups (p<0.01). Based on this significance, the researchers used ROC analysis to estimate a cut-off point for AMH. The researchers detected the good responders with an AMH level 1.90 or above, with 87.50% sensitivity, 66.67% specificity, 87.50% positive prediction, and 66.67% negative prediction (AUC=0.777, p<0.01). CONCLUSION: Basal AMH levels can be used as an indicator to determine the ovarian response in women undergoing ICSI. AMH can be used to predict the number of mature oocytes that can be collected during treatment and the number of oocytes that can be fertilized. However, AMH is not a valuable tool to evaluate oocyte quality, the development of high-quality embryos, or pregnancy conception. PMID- 26131014 TI - First successful pregnancies following embryo selection using Time-lapse technology in Iran: Case report. AB - BACKGROUND: Embryo selection is a vital part of in vitro fertilization (IVF) programs, with morphology-based grading systems having been widely used for decades. Time-lapse imaging combined with embryo morph kinetics may proffer a non invasive means for improving embryo selection. We report the first ongoing and chemical pregnancies using Time-lapse embryo scope to select best embryos for transfer in Iran. CASES: A case with tubal factor infertility was admitted to IVF program with normozoospermia. After ovarian hyper stimulation, 6 COCs were retrieved and inseminated with 25,000 progressive sperms/ oocyte. Five zygotes were placed individually into the micro wells of equilibrated embryo scope dish for Time-lapse observation, and incubated at 37 degrees C, 5% CO2. On day 3, single embryo transfer (SET) took place based on kinetic parameters of the embryos. Clinical pregnancy was confirmed 7 weeks after SET. The second case with history of previous ICSI failure was admitted with azoospermia. Nine MII oocytes underwent ICSI, and incubated in Time-lapse facilities. The rest of procedures were followed as described for case 1. Chemical pregnancy was confirmed 15 days after SET. CONCLUSION: This approach opens a way to select best embryo non invasively for SET; thus, increasing implantation, while reducing multiple pregnancy complications. PMID- 26131015 TI - CSACI position statement: epinephrine auto-injectors and children < 15 kg. AB - Epinephrine (adrenaline) is the treatment of choice for anaphylaxis. While other medications, including H1-antihistamines, H2-antihistamines, corticosteroids, and inhaled beta-2 agonists are often used to treat anaphylaxis in the emergency setting, none of these medications has been shown to reverse anaphylaxis. Fatal anaphylaxis is related to the delayed use of epinephrine. In community settings, epinephrine is available as an auto-injector in two doses, 0.15 mg and 0.3 mg. The recommended dose for children is 0.01 mg per kilogram. For infants at risk of anaphylaxis in the community, there are few options with regard to providing an optimal epinephrine dose for first-aid treatment. The Canadian Society of Allergy and Immunology (CSACI) therefore recommends, for the child weighing less than 15 kg, given the lack of a suitable alternative, prescribing the 0.15 mg epinephrine autoinjector. Adverse effects of an epinephrine dose of 0.15 mg given intramuscularly in infants or children weighing less than 15 kg are expected to be mild and transient at the plasma epinephrine concentrations achieved; therefore, these effects need to be measured against the consequences of not receiving epinephrine at all, which can include fatality. PMID- 26131016 TI - Ougan (Citrus reticulata cv. Suavissima) flavedo extract suppresses cancer motility by interfering with epithelial-to-mesenchymal transition in SKOV3 cells. AB - BACKGROUND: Ougan (Citrus reticulata cv. Suavissima) flavedo extract (OFE) exhibited potential anti-tumor effects with unclear underlying mechanisms. This study aims to evaluate the potential anti-metastatic activities of OFE on human ovarian cancer cells, and investigate its inhibitory effect on epithelial-to mesenchymal transition (EMT). METHODS: Ougan fruits were harvested. Flavedo tissues were separated and made into freeze-dried powder. Then OFE were extracted from the powder. The components of OFE were identified by the high performance liquid chromatography system with a detection wavelength of 280 nm for flavanones and 330 nm for polymethoxylated flavones. Cell viability was assessed by Sulforhodamine B assay. The effects on cancer cell migration and motility were evaluated by wound-healing and transwell assays. The mechanisms of action were investigated by examining the modulation by OFE on EMT-related signaling pathways at the concentrations of 4 MUg/mL and 20 MUg/mL, using qRT-PCR and western blot analyses. RESULTS: Non-cytotoxic concentrations of OFE significantly suppressed the cellular migration (4 MUg/mL, P = 0.005 vs. control group; 20 MUg/mL, P = 0.003 vs. control group) and motility (4 MUg/mL, P < 0.001 vs. control group; 20 MUg/mL, P < 0.001 vs. control group) of SKOV3 cells, and inhibited transforming growth factor-beta1 (TGF-beta1)-induced E-cadherin loss (4 MUg/mL, P = 0.002 vs. control group; 20 MUg/mL, P = 0.001 vs. control group) and mesenchymal marker upregulation, e.g., N-cadherin (4 MUg/mL, P = 0.027 vs. control group; 20 MUg/mL, P = 0.013 vs. control group), vimentin (4 MUg/mL, P = 0.036 vs. control group; 20 MUg/mL, P = 0.015 vs. control group) and fibronectin (4 MUg/mL, P < 0.001 vs. control group; 20 MUg/mL, P < 0.001 vs. control group). CONCLUSIONS: The anti metastatic ability of OFE inhibited EMT by interfering with the canonical TGF beta1-SMAD-Snail/Slug axis. PMID- 26131017 TI - A major shift of viral and nutritional risk factors affects the hepatocellular carcinoma risk among Ivorian patients: a preliminary report. AB - Hepatocellular carcinoma (HCC) is a major public health concern in Sub-Saharan Africa. Early research in Ivory Coast showed that chronic hepatitis B and aflatoxin B1 exposure were the two most important etiological agents of HCC in the country but, surprisingly, no survey analyzing HCC etiologies has been conducted since decades. In a preliminary report, we characterized for hepatitis B and C markers 30 consecutive cases of HCC recruited from Abidjan hospitals between June 2011 and December 2012. Nutritional and lifestyle features of patients were analyzed as well. The mean age of the patients was 53 +/- 15 years with a sex ratio (M:F = 2.7). HBsAg was the most frequent viral marker in the series (63 %). All HBV isolates belonged to genotype E. With regards to regional standard, anti-HCV reached a very high level (47 %) in the present series. Hepatitis C was more frequent among patients living outside Abidjan (83 vs 23 %, P = 0.009). Patients living in Abidjan were significantly younger than individual living elsewhere in the country (48 +/- 14 vs 60 +/- 16 years old, P = 0.038) reflecting a possible role for local environmental pollution in tumor progression. Finally, we observed that patients born in Mande/Gur-speaking regions (North) were younger (48 +/- 14 vs 59 +/- 15, P = 0.05) and consumed maize more frequently (80 vs 26 %, P = 0.009) than other patients. Interestingly, maize consumption was associated with a trend for aminotransferases elevation (mean = 1.7-1.8 fold, P = 0.06) suggesting a direct hepatic toxicity of this staple food in Ivory Coast. In conclusion, our work indicates that HCC epidemiology underwent recently major drifts in Ivory Coast. PMID- 26131018 TI - The virtual institution: cross-sectional length of stay in general adult and forensic psychiatry beds. AB - BACKGROUND: Length of stay in psychiatric hospitals interests health service planners, economists and clinicians. At a systems level it is preferable to study general adult and forensic psychiatric beds together since these are likely to be inter-dependent. We examined whether patients were placed according to specialist need or according to their cross-sectional length of stay. METHODS: A one night census of all registered mental nursing home (RMNH) beds was carried out for a defined catchment area of 1.2 m population in north London in November 1999. This included all public sector psychiatric hospital beds, independent sector and forensic beds in and outside the catchment area. Cross-sectional length of stay was defined as time since the date of admission from the community. Log rank (Mantel-Cox) Chi squared was used to test for differences between groups and hierarchical logistic regression for statistical modelling. RESULTS: There were 1,085 occupied psychiatric beds. Cross-sectional LOS was greater than 365 days in 43.5%. Forensic beds had longer cross-sectional LOS than general beds. LOS increased with the level of therapeutic security from open through low, medium and high secure. Cross-sectional LOS was shorter for open hospital beds than community RMNH beds, shorter for informal patients than those detained under civil mental health law, and longest for forensic detentions. Longest cross sectional LOS were for patients placed in RMNHs in the community, 10.7% of whom were 'forensic' as were 25.4% of low secure patients. Designated length of stay (acute, rehab/medium term and long term) was also associated with increasing cross-sectional LOS. In regression analysis only three variables contributed to a model of cross-sectional LOS, commissioning status (general or forensic), designated length of stay and designated level of therapeutic security. CONCLUSIONS: Studying cross-sectional LOS for whole systems (all psychiatric beds) is essential for operational health service management. At the time of this survey 'forensic' status was the main way of accessing long term high dependency places. This has been an organic development over time, a response to patient needs rather than the outcome of any specific policy or plan. PMID- 26131019 TI - Perceived behavioral problems of school aged children in rural Nepal: a qualitative study. AB - BACKGROUND: Studies on child behavioral problems from low and middle income countries are scarce, even more so in Nepal. This paper explores parents', family members' and teachers' perceptions of child behavioral problems, strategies used and recommendations to deal with this problem. METHOD: In this study, 72 free list interviews and 30 Key Informant Interviews (KII) were conducted with community members of Chitwan district in Nepal. RESULT: The result suggest that addictive behavior, not paying attention to studies, getting angry over small issues, fighting back, disobedience, and stealing were the most commonly identified behavioral related problems of children, with these problems seen as interrelated and interdependent. Results indicate that community members view the family, community and school environments as being the causes of child behavioral problems, with serious impacts upon children's personal growth, family harmony and social cohesion. The strategies reported by parents and teachers to manage child behavioral problems were talking, listening, consoling, advising and physical punishment (used as a last resort). CONCLUSIONS: As perceived by children and other community dwellers, children in rural Nepalese communities have several behavioral related problems. The findings suggest that multi-level community-based interventions targeting peers, parents, teachers and community leaders could be a feasible approach to address the identified problems. PMID- 26131020 TI - Ethical challenges for medical professionals in middle manager positions: a debate article. AB - BACKGROUND: Demographic changes increase the financing needs of all social services. This change also generates new and complex demands on the medical staff. Accordingly, medical professionals in middle management positions hold a characteristic sandwich position between top management and the operational core. This sandwich position often constitutes new challenges. In the industrial field, the growing importance of the middle management for the company's success has already been recognized. Accordingly, the growing demand on economy urges an analysis for the medical field. DISCUSSION: While there are nearly no differences in the nature of the tasks of medical middle manager in the areas of strategy, role function, performance pressure and qualifications compared to those tasks of the industrial sector, there are basic differences as well. Especially the character of "independence" of the medical profession and its ethical values justifies these differences. Consequently, qualification of medical professionals may not be solely based on medical academic career. It is also based on the personal ability or potential to lead and to manage. SUMMARY: Above all, the character of "independence" of the medical profession and its ethical values justifies medical action that is based on the patient's well-being and not exclusively on economic outcomes. In the future, medical middle managers are supposed to achieve an optimized balance between a patient-centered medicine and economic measures. It will be a basic requirement that middle managers accept their position and the resultant tasks putting themselves in a more active position. Because of that, middle managers can become "value-added bridge builders". PMID- 26131021 TI - TaxKB: a knowledge base for new taxane-related drug discovery. AB - BACKGROUND: Taxanes are naturally occurring compounds which belong to a powerful group of chemotherapeutic drugs with anticancer properties. Their current use, clinical efficacy, and unique mechanism of action indicate their potentiality for cancer drug discovery and development thereby promising to reduce the high economy associated with cancer worldwide. Extensive research has been carried out on taxanes with the aim to combat issues of drug resistance, side effects, limited natural supply, and also to increase the therapeutic index of these molecules. These efforts have led to the isolation of many naturally occurring compounds belonging to this family (more than 350 different kinds), and the synthesis of semisynthetic analogs of the naturally existing molecules (>500), and has also led to the characterization of many (>1000) of them. A web-based database system on clinically exploitable taxanes, providing a link between the structure and the pharmacological property of these molecules could help to reduce the druggability gap for these molecules. RESULTS: Taxane knowledge base (TaxKB, http://bioinfo.au-kbc.org.in/taxane/Taxkb/), is an online multi-tier relational database that currently holds data on 42 parameters of 250 natural and 503 semisynthetic analogs of taxanes. This database provides researchers with much-needed information necessary for drug development. TaxKB enables the user to search data on the structure, drug-likeness, and physicochemical properties of both natural and synthetic taxanes with a "General Search" option in addition to a "Parameter Specific Search." It displays 2D structure and allows the user to download the 3D structure (a PDB file) of taxanes that can be viewed with any molecular visualization tool. The ultimate aim of TaxKB is to provide information on Absorption, Distribution, Metabolism, and Excretion/Toxicity (ADME/T) as well as data on bioavailability and target interaction properties of candidate anticancer taxanes, ahead of expensive clinical trials. CONCLUSION: This first web-based single-information portal will play a central role and help researchers to move forward in taxane-based cancer drug research. PMID- 26131022 TI - Tests detecting biomarkers for screening of colorectal cancer: What is on the horizon? AB - AIM: To identify new and emerging screening tests for colorectal cancer (CRC) that involves detection of various biomarkers like blood, DNA and RNA in samples of faeces, tissue or blood. Current practice: Screening for CRC can be done by bowel visualisation techniques and tests that measure biomarkers. The Bowel Cancer Screening Programme (BCSP) in England uses a guaiac faecal occult blood test. METHODS: The strategy was to search available literature, identify developers and contact them for relevant information. Advice from experts was sought on potential utility and likely impact of identified technologies on the BCSP. RESULTS: Ninety-three companies and five research groups were contacted. Sixty-nine relevant tests were identified. Detailed information was available for 48 tests, of these 73% were CE marked and the remainder were considered as emerging. Forty-nine tests use immunochemical methods to detect occult blood in faeces. Eight, four and two tests detect biomarkers in a sample of blood, or exfoliated cells either shed in faeces or collected from rectal mucosa respectively. Six tests were grouped as 'other tests'. Most of the identified tests are performed manually and give qualitative detection of biomarkers. CONCLUSION: Variation in test performance and characteristics was observed amongst the 69 identified tests. Automated, quantitative FIT with a variable cut off are the preferred approach in the BSCP. However the units used to report FITs results do not enable comparison across products. Tests detecting biomarkers other than occult blood are more specific to neoplasms but have limited sensitivity due to the heterogeneity of cancer. Research is ongoing to identify an optimal panel of biomarkers, simplifying and automating the test, and reducing the cost. PMID- 26131023 TI - Violence: heightened brain attentional network response is selectively muted in Down syndrome. AB - BACKGROUND: The ability to recognize and respond appropriately to threat is critical to survival, and the neural substrates subserving attention to threat may be probed using depictions of media violence. Whether neural responses to potential threat differ in Down syndrome is not known. METHODS: We performed functional MRI scans of 15 adolescent and adult Down syndrome and 14 typically developing individuals, group matched by age and gender, during 50 min of passive cartoon viewing. Brain activation to auditory and visual features, violence, and presence of the protagonist and antagonist were compared across cartoon segments. fMRI signal from the brain's dorsal attention network was compared to thematic and violent events within the cartoons between Down syndrome and control samples. RESULTS: We found that in typical development, the brain's dorsal attention network was most active during violent scenes in the cartoons and that this was significantly and specifically reduced in Down syndrome. When the antagonist was on screen, there was significantly less activation in the left medial temporal lobe of individuals with Down syndrome. As scenes represented greater relative threat, the disparity between attentional brain activation in Down syndrome and control individuals increased. There was a reduction in the temporal autocorrelation of the dorsal attention network, consistent with a shortened attention span in Down syndrome. Individuals with Down syndrome exhibited significantly reduced activation in primary sensory cortices, and such perceptual impairments may constrain their ability to respond to more complex social cues such as violence. CONCLUSIONS: These findings may indicate a relative deficit in emotive perception of violence in Down syndrome, possibly mediated by impaired sensory perception and hypoactivation of medial temporal structures in response to threats, with relative preservation of activity in pro-social brain regions. These findings indicate that specific genetic differences associated with Down syndrome can modulate the brain's response to violence and other complex emotive ideas. PMID- 26131024 TI - A Novel Approach against Vascular Intimal Hyperplasia Through the Suppression of Girdin. AB - Intimal hyperplasia is an impediment to patency in both arteries after percutaneous angioplasty (PTA) and veingraft. It is well known that migration and proliferation of vascular smooth muscle cells (SMCs) influence the vascular remodeling process, there are no therapies to prevent intimal hyperplasia of post PTA arteries and vein grafts. Girdin (girders of actin filaments), also known as Galpha-interacting vesicle associated protein (GIV) is a novel actin-binding Akt substrate.Girdin is highly expressed in limited types of cells such as smooth muscle cells, neuroblasts, and cancer cells. Girdin is involved in the cell migration, proliferation and remodeling of actin filaments. This study revealed that Girdin is involved with intimal hyperplasia in carotid arteries after balloon injury and vein grafts and vascular SMCs migration and proliferation. There are suggestions that Girdin has pivotal roles in migration and proliferation of vascular SMCs and that gene therapy targeting Girdin could be a novel therapeutic strategy for restenosis after PTA and vein graft failure. PMID- 26131025 TI - Deployment Accuracy of the Conformable GORE((r)) TAG((r)) Thoracic Endoprosthesis in the Treatment of Zones 2 and 3 Aortic Arch Aneurysms Compared with the Previous TAG((r)). AB - PURPOSES: When placing stent grafts, deployment accuracy and birdbeaking due to inadequate conformability and device apposition along the inner curvature of the arch have been encountered. The new Conformable GORE(r) TAG(r) Thoracic Endoprosthesis (CTAG) is designed to have enhanced compression resistance and improved conformability in difficult anatomy. The present study compared the deployment accuracy and conformability of the CTAG Device with TAG Device. METHOD: Deployment accuracy and birdbeaking was compared of CTAG Device and TAG Device implantation for initial treatment of thoracic aortic aneurysm conducted by our department between March 2010 and March 2012. Deployment accuracy was defined as the distance between the actual and intended device implantation locations measured from DSA images. RESULTS: Deployment accuracy at the time of implantation (mean +/- SD) was significantly better for the CTAG Device compared to the TAG Device (2.2 +/- 1.7 mm vs. 4.4 +/- 3.0 mm, P <0.05). Also, while birdbeaking was seen in 8 of 20 cases (40%) for the TAG Device, it was only seen in 1 of 12 cases (8%) for the CTAG Device. CONCLUSION: The present study found enhanced deployment accuracy and conformability along the aortic arch using the CTAG Device compared to the previous-generation TAG Device. PMID- 26131026 TI - Comparison of Long-Term Clinical Outcomes after Drug-Eluting Stent Implantation in Patients with Coronary Artery Disease with and without Prior Cerebral Infarction. AB - OBJECTIVE: To compare the clinical and angiographic outcomes after implantation of drug-eluting stents (DESs) in patients with coronary artery disease (CAD) with or without prior cerebral infarction. MATERIALS AND METHODS: Ninety-eight consecutive patients (130 lesions) who underwent successful coronary DES implantation were prospectively classified into two groups: those with a clinical history of symptomatic cerebral infarction (cerebral infarction group, 49 patients, 69 lesions) and those without a clinical history of symptomatic cerebral infarction (noncerebral infarction group, 49 patients, 61 lesions). The primary endpoint was defined as death, nonfatal myocardial infarction, and cerebrovascular events. RESULTS: The Kaplan-Meier method was used to create a primary endpoint curves to determine the time-dependent cumulative primary endpoint-free rate, which were compared using the log-rank test. The incidence of primary endpoints was higher in the cerebral infarction group than in the noncerebral infarction group (p = 0.0075). The Cox proportional hazards regression model for primary endpoint identified prior cerebral infarction (p = 0.0331, hazard ratio = 2.827) and patients with peripheral artery disease (p = 0.0271, hazard ratio = 2.757) as explanatory factors. CONCLUSION: The results showed that clinical outcomes were poorer in patients with CAD who had prior cerebral infarctions than in those who did not have infarction. PMID- 26131027 TI - Hybrid Repair of Proximal Subclavian Artery Aneurysm. AB - OBJECTIVE: Conventional open repair for proximal subclavian artery aneurysms (SCAAs) requires cardiopulmonary bypass. However, patients with proximal SCAA can be treated with hybrid repair. METHODS: Between 2007 and 2012, we performed hybrid repair to treat six consecutive patients with proximal SCAA (three left SCAAs, one right aberrant SCAA, two right SCAAs). Their median age was 73.5 [70 87] years, and the size of their aneurysm was 33.5 [30-45] mm. Thoracic endovascular aneurysm repair (TEVAR) only was used for one patient with left SCAA, TEVAR and supra-aortic bypass for two with left SCAA and one with right aberrant SCAA, and endovascular repair with reconstruction of the vertebral artery using the saphenous vein graft (SVG) for two with right SCAA. RESULTS: The follow-up duration was 3.7 [0.2-6.8] years. There was no 30-day mortality and only one early complication consisting of a minor stroke after TEVAR for shaggy aorta. Two late deaths occurred, one caused by cerebral infarction due to occlusion of SVG to the dominant vertebral artery 2 months after the operation and the other by aortic dissection 5 years postoperatively. CONCLUSIONS: Hybrid repair can be a less-invasive alternative for proximal SCAA. Revascularization of neck vessels and TEVAR should be performed very carefully to prevent neurologic complications. PMID- 26131028 TI - Differentiation of High and Low Output Lymphatic Failure Using Qualitative Lymphangioscintigraphy. AB - PURPOSE: To use qualitative lymphangioscintigraphy (LAS) findings to differentiate leg edema caused by high and low output lymphatic failure. METHODS: LAS was performed in legs with secondary lymphedema (LE), i.e., low output failure (N = 79), and functional venous insufficiency (FVI), i.e., high output failure (N = 56), and normal legs (N = 26). Whole body images were obtained, 15, 60, and 180 min after technetium-99m injection. The rate and timing of visualization of lymphatic structures, washout out of tracer, and presence of dermal backflow were assessed. RESULTS: The most significant finding for differentiating LE from other conditions was not the visualization of lymphatic structures, but the washout of the tracer from the leg trunk (LE 27%, FVI 100%, normal leg 100%, P <.0001). On the other hand, the most significant finding for differentiating FVI from other legs was the visualization of inguinal lymph nodes at 15 min (LE 11%, FVI 82%, normal leg 8%, P <.0001). CONCLUSIONS: We found that the lack of washout from the leg trunk was most suggestive of a low output status of the lymphatic system, while earlier visualization of inguinal lymph nodes was suggestive of a high output status. PMID- 26131029 TI - A Case of External Compression of Femoral Vein by the Enlarged Iliopsoas Bursa with Long Term Edema. AB - The iliopsoas bursa is the largest bursa in the region of hip joint. It is unusual that these bursa become symptomatic. However the bursa can compress femoral vein, leading to lower extremity edema. A 58-year-old man was referred to our department for his unilateral leg edema which had been treated as deep vein thrombosis without any favorable response. Magnetic resonance angiography was performed, which demonstrated enlarged iliopsoas bursa compressing his femoral vein. Surgical removal of the bursa was performed. The postoperative course was uneventful, and the patient is free from symptoms with no evidence of recurrence. PMID- 26131030 TI - Neovascular Glaucoma Post Carotid Endarterectomy: A Case Report and Review of the Literature. AB - Carotid endarterectomy is a standard vascular surgical procedure performed worldwide and encompasses multiple risks including cerebral hyperperfusion syndrome, stroke, carotid dissection and aneurysmal formation, all of which are well documented in the literature. However, neovascular glaucoma manifesting post carotid endarterectomy, is extremely rare and can have disastrous consequences if left undiagnosed. In this article, we present one such case of neovascular glaucoma manifesting post carotid endarterectomy and review the available literature on this uncommon entity. PMID- 26131031 TI - Hybrid Three-Stage Repair for Extended Thoracoabdominal Aortic Aneurysm: Report of A Case. AB - A 67-year-old man complicated with back pain. The computed tomography (CT) scan showed an extended thoracoabdominal aneurysm. We successfully performed a three stage hybrid repair using the visceral-renal debranching technique. For the first stage operation we performed Y-grafting with the debranching technique to create a distal landing zone. Then, for the second stage operation, we performed the hybrid procedure including total arch replacement (TAR) and antegrade stent graft deployment to create a proximal landing zone. Finally, additional thoracic endovascular aortic repair (TEVAR) between the distal and proximal landing zones was successfully accomplished as the third stage operation. PMID- 26131032 TI - Management of Aortic Replacement-Induced Chylothorax by Lipiodol Lymphography. AB - Chylothorax is a rare but serious complication of thoracic aortic surgery, leading to malnutrition, respiratory insufficiency, and prolonged hospital stay. In this article, we describe the successful treatment of a case of intractable chylothorax by lipiodol lymphography. The patient was a 39-year-old man who underwent descending aortic replacement for a remaining dissected aneurysm after total arch replacement. Chylothorax developed postoperatively. After complete oral intake cessation, total parenteral nutrition, and plasmatic factor XIII administration, lipiodol lymphography detected the chyle leakage location and subsequently decreased pleural effusion. The patient recovered uneventfully and was discharged on postoperative day 30 without any complications. PMID- 26131033 TI - Chronic Contained Abdominal Aortic Aneurysm Rupture Mimicking Vertebral Spondylodiscitis: A Case Report. AB - A 63-year-old Caucasian male presented with a 4-month history of low back pain associated with bilateral intermittent claudication. A contrast enhanced CT scan demonstrated a 4 cm abdominal aortic aneurysm (AAA), along with severe bilateral aorto-iliac disease, a right psoas collection, and extensive vertebral erosion. An MRI of the lumbar spine suggested spondylodiscitis at L4-L5. After an unsuccessful and prolonged course of antibiotics, a decision was ultimately made to repair the aneurysm and bypass the aorto-iliac disease. Intra-operatively, a chronic contained rupture (CCR) involving the posterior aortic wall was encountered and repaired with an aorto-bifemoral bypass graft. PMID- 26131034 TI - Urgent Surgical Management of Deep Femoral Artery Aneurysm in a Patient with Pre Vasculo-Behcet Status. AB - We report a case of deep femoral artery (DFA) aneurysm associated with pre vasculo-Behcet status. A 34-year-old man with a history of recurring oral and genital ulcers was admitted complaining of worsening left thigh pain over the previous 30 days. Computed tomography showed a left DFA aneurysm (60 mm * 70 mm), concomitant aneurysms in the popliteal and carotid arteries, and deep vein thrombosis. Active pre-vasculo-Behcet status was diagnosed, and DFA ligation was performed urgently. Remission was achieved with postoperative prednisolone and colchicine without vascular complications. DFA aneurysm and vascular pathologies were successfully managed by ligation surgery and medical therapy. PMID- 26131035 TI - Three Case Report of Spontaneous Isolated Dissection of the Superior Mesenteric Artery-With an Algorithm Proposed for the Management. AB - Spontaneous isolated dissection of the superior mesenteric artery (SID-SMA) is a rare condition, and there is still no consensus on optimal management. Here, we present three cases of SID-SMA, that were treated by surgical revascularization with urgent iliomesenteric bypass surgery without intestine resection, endovascular therapy with stent placement, and conservative management. The purpose of this study is to review these three cases and propose an algorithm for optimal management of SID-SMA. PMID- 26131036 TI - A Case of Takayasu's Arteritis with Total Occlusion of the Abdominal Aorta Treated Only with Oral Medication for More Than 40 Years. AB - Takayasu's arteritis affects most commonly young women, often causing stenotic and occasionally dilated lesions of the medium-to-large-sized arteries with an acute inflammatory signs and symptoms. Here, we report a rare case of Takayasu's arteritis with total occlusion of the abdominal aorta, which was successfully treated with medication alone and asymptomatic over 40 years. Magnetic resonance imaging revealed total occlusion of the abdominal aorta and stenosis of the right carotid artery. This is the first report of a very rare case of Takayasu's arteritis, in which medical treatment only was successful against total occlusion of the abdominal aorta. PMID- 26131037 TI - Single-Stage Repair of Thoracic Aortic Aneurysm through a Median Sternotomy in a Patient with Pseudocoarctation of the Aorta and Severe Aortic Valve Stenosis. AB - Pseudocoarctation of the aorta is a rare anomaly and considered a benign condition. Pseudocoarctation of the aorta has been associated with aneurysm formation in the thoracic aorta, which may cause sudden rupture or dissection. Thus, the presence of an aneurysm in combination with pseudocoarctation of the aorta is thought to be an indication for surgery. We present a case of pseudocoarctation of the aorta associated with thoracic aortic aneurysm and severe aortic valve stenosis with a bicuspid aortic valve. In our case, single stage repair was performed through a median sternotomy using our "pleural-window approach." PMID- 26131038 TI - Life-Saving Embolization in a Patient with Recurrent Shock Due to a Type II Endoleak after Endovascular Aortic Repair for a Ruptured Abdominal Aortic Aneurysm. AB - A man in his 80s underwent urgent endovascular aortic repair (EVAR) for a ruptured abdominal aortic aneurysm (RAAA). Surgery was completed without apparent complications, and the patient was returned to the Cardiac Care Unit. Two hours later, he again developed shock, and contrast-enhanced Computed Tomography showed extravasation from a type II endoleak (T2EL) involving the IMA. Transcatheter arterial embolization (TAE) was immediately performed, and the patient's vital signs stabilized soon after embolization. Abdominal compartment syndrome was suspected during the procedure, so a retroperitoneal hematoma evacuation was performed. The patient's postoperative course was satisfactory, and he transferred to another hospital. EVAR for RAAA would be useful, but it is necessary to be considered that T2EL can cause the aggravation of unstable circulation. PMID- 26131039 TI - Perception of community pharmacists towards the barriers to enhanced pharmacy services in the healthcare system of Dubai: a quantitative approach. AB - BACKGROUND: In many developing countries, pharmacists are facing many challenges while they try to enhance the quality of services provided to patients approaching community pharmacies. OBJECTIVE: To explore perception of community pharmacists in Dubai regarding the obstacles to enhanced pharmacy services using a part of the results from a nation-wide quantitative survey. METHODS: A questionnaire was distributed to 281 full-time licensed community pharmacists in Dubai. The questionnaire had 5 inter-linked sections: demographic information, information about the pharmacy, interaction with physicians, pharmacists' current professional role, and barriers to enhanced pharmacy services. RESULTS: About half of the respondents (45.4%, n=90) agreed that pharmacy clients under-estimate them and 52.5% (n=104) felt the same by physicians. About 47.5% (n=94) of the respondents felt that they are legally unprotected against profession's malpractice. Moreover, 64.7% (n=128) stated that pharmacy practice in Dubai turned to be business-focused. In addition, 76.8% (n=252) found that one of the major barriers to enhanced pharmacy services is the high business running cost. Pharmacists screened tried to prove that they are not one of the barriers to optimized pharmacy services as 62.7% (n=124) disagreed that they lack appropriate knowledge needed to serve community and 67.7% (n=134) gave the same response when asked whether pharmacy staff lack confidence when treating consumers or not. CONCLUSIONS: Although being well established within the community, pharmacists in Dubai negatively perceived their own professional role. They stated that there are number of barriers which hinder optimized delivery of pharmacy services like under-estimation by pharmacy clients and other healthcare professionals, pressure to make sales, and high running cost. PMID- 26131040 TI - Burden and associated pathologies in family caregivers of Alzheimer's disease patients in Spain. AB - OBJECTIVES: To evaluate the profile of family caregivers of Alzheimer's disease patients, identify any signs of psychopathology, quantify the level of perceived burden on the caregiver, and determine the caregiver's relationship with their pharmacist. METHODS: A cross-sectional study was conducted at a community pharmacy in Pontevedra, Spain. Demographic variables were collected, and the following questionnaires were administered: the Beck Depression Inventory-II, STAI-Anxiety Questionnaire, Zarit Burden Scale, family APGAR scale, and the Duke UNC questionnaire. RESULTS: The typical caregiver profile consists of a 55-year old first degree relative (mostly daughters) with a primary education who belongs to a functional or mildly dysfunctional family. Nearly one quarter (24%) of caregivers had a high perception of burden, with anxiety in 20% of caregivers and symptoms of depression in 20%. Family caregivers usually went to the same pharmacy as the patients (96%), were treated with psychotropic drugs (68%), and interacted with the pharmacist (92%). CONCLUSION: This study confirmed that psychological distress and burden is present among family caregivers. Care for caregivers should be integrated into patient care as part of a national plan, including grants and subsidies, which will result in better care of Alzheimer's patients. Pharmacists are the most accessible health care professionals and can provide information about Alzheimer's disease management to caregivers to ease the burden of care. PMID- 26131041 TI - Comparison of anti-retroviral therapy treatment strategies in prevention of mother-to-child transmission in a teaching hospital in Ethiopia. AB - BACKGROUND: More than 90% of Human immunodeficiency virus (HIV) infection in children is acquired due to mother-to-child transmission, which is spreading during pregnancy, delivery or breastfeeding. OBJECTIVE: To determine the effectiveness of highly active antiretroviral and short course antiretroviral regimens in prevention of mother-to-child transmission of HIV and associated factors Jimma University Specialized Hospital (JUSH). METHOD: A hospital based retrospective cohort study was conducted on HIV infected pregnant mothers who gave birth and had follow up at anti-retroviral therapy (ART) clinic for at least 6 months during a time period paired with their infants. The primary and secondary outcomes were rate of infant infection by HIV at 6 weeks and 6 months respectively. The Chi-square was used for the comparison of categorical data multivariate logistic regression model was used to identify the determinants of early mother-to-child transmission of HIV at 6 weeks. Cox proportional hazard model was used to analyze factors that affect the 6 month HIV free survival of infants born to HIV infected mothers. RESULTS: A total of 180 mother infant pairs were considered for the final analysis, 90(50%) mothers received single dose nevirapine (sdNVP) designated as regimen-3, 67 (37.2%) mothers were on different types of ARV regimens commonly AZT + 3TC + NVP (regimen-1), while the rest 23 (12.8%) mothers were on short course dual regimen AZT + 3TC + sdNVP (regimen-2). Early mother-to-child transmission rate at 6 weeks for regimens 1, 2 and 3 were 5.9% (4/67), 8.6% (2/23), and 15.5% (14/90) respectively. The late cumulative mother-to-child transmission rate of HIV at 6 months regardless of regimen type was 15.5% (28/180). Postnatal transmission at 6 months was 28.5% (8/28) of infected children. Factors that were found to be associated with high risk of early mother-to-child transmission of HIV include duration of ARV regimen shorter than 2 months during pregnancy (OR=4.3, 95%CI =1.38-13.46), base line CD4 less than 350 cells/cubic mm (OR=6.98, 95%CI=0.91-53.76), early infant infection (OR=5.4, 95%CI=2.04-14.4), infants delivered home (OR=13.1, 95%CI=2.69-63.7), infant with birth weight less than 2500 g (OR=6.41, 95%CI=2.21-18.61), and mixed infant feeding (OR=6.7, 95%CI=2.2-20.4). Antiretroviral regimen duration less than 2 months, maternal base line CD4 less than 350 cells/cubic mm and mixed infant feeding were also important risk factors for late infant infection or death. CONCLUSION: The effectiveness of multiple antiretroviral drugs in prevention of early mother-to-child transmission of HIV was found to be more effective than that of single dose nevirapine, although, the difference was not statistically significant. But in late transmission, a significant difference was observed in which infants born to mother who received multiple antiretroviral drugs were less likely to progress to infection or death than infants born to mothers who received single dose nevirapine. PMID- 26131042 TI - Prescription drug monitoring program utilization in Kentucky community pharmacies. AB - OBJECTIVE: Identify characteristics of Kentucky community pharmacists and community pharmacists' practice environment associated with utilization of the Kentucky All Schedule Prescription Electronic Reporting Program (KASPER). METHODS: Surveys were mailed to all 1,018 Kentucky pharmacists with a KASPER account and an additional 1,000 licensed pharmacists without an account. Bivariate analyses examined the association between KASPER utilization and practice type (independent or chain) and practice location (rural or urban). A multivariate Poisson regression model with robust error variance estimated risk ratios (RR) of KASPER utilization by characteristics of pharmacists' practice environment. RESULTS: Responses were received from 563 pharmacists (response rate 27.9%). Of these, 402 responses from community pharmacists were included in the analyses. A majority of responding pharmacists (84%) indicated they or someone in their pharmacy had requested a patient's controlled substance history since KASPER's inception. Bivariate results showed that pharmacists who practiced in independent pharmacies reported greater KASPER utilization (94%) than pharmacists in chain pharmacies (75%; p<0.001). Multivariate regression results found utilization of KASPER varied significantly among practice environments of community pharmacists with those who practiced in an urban location (RR: 1.11; [1.01-1.21]) or at an independent pharmacy (RR: 1.27; [1.14-1.40]) having an increased likelihood of KASPER utilization. CONCLUSION: Utilization of KASPER differs by community pharmacists' practice environment, predominantly by practice type and location. Understanding characteristics of community pharmacists and community pharmacists' practice environment associated with PDMP use is necessary to remove barriers to access and increase utilization thereby increasing PDMP effectiveness. PMID- 26131043 TI - An exploratory study of the patient experience of pharmacist supplementary prescribing in a secondary care mental health setting. AB - BACKGROUND: Management of chronic disease has become an increasing challenge to the National Health Service in the United Kingdom. The introduction of supplementary prescribing was seen as a possible mechanism to address the needs of this patient group. Individuals with mental illness were considered particularly suitable for management in this way. OBJECTIVE: To explore the views and experiences of patients with mental illness on being managed by a pharmacist supplementary prescriber in a secondary care outpatient setting. METHODS: A study of patient experiences utilising semi-structured interviews and self-completion diaries was adopted. Eleven patients participated in the study. Data were analysed utilising code and retrieve, and content analysis respectively. RESULTS: Patients valued the increased accessibility to, and continuity of, their prescriber compared with their experience of other healthcare professionals. Patients reported they were able to trust the pharmacist's knowledge of medication, were provided with sufficient information regarding reasons for treatment and side effects, and felt that they had an active role in decisions concerning their healthcare. CONCLUSIONS: This exploratory study showed that patients had positive views of being managed by a supplementary prescriber. However, it should be noted that the number of participants was small. It is therefore important that further, more wide ranging research is conducted to evaluate pharmacist prescribing within mental health settings. PMID- 26131044 TI - Tyrosine kinase inhibitors in patients with chronic myelogeneous leukemia: defining the role of social risk factors and non-adherence to treatment. AB - OBJECTIVE: To assess the role of social risk factors on adherence to tyrosine kinase inhibitors (TKI) therapy in chronic myeloid leukemia (CML) patients. METHODS: This is a retrospective study and eligible patients were adults with CML on TKI treatment. Cases of no adherence to treatment were confirmed during pharmacists' consultation (patient-reported adherence). Baseline characteristics between groups were compared between cases and controls groups. Risk factors identified in bivariate analysis (p<0.2) were included in multivariate model. A qualitative investigation assessed whether such predictors of non-adherence had causal relationship. RESULTS: Of 151 patients with CML consulted by pharmacists, 21% had adherence problems. Despite patients with secondary school (p=0.03), most of investigated social risk factors did not differ between groups. However, by using a qualitative approach, patients' level of education could not explain low adherence rates behavior. CONCLUSIONS: Social determinants of health, herein investigated, were unlikely to predict adherence to treatment. Regression techniques may lead to untrue statements, so future researches should consider investigating the causes, not only the statistical estimates. PMID- 26131045 TI - Views and attitudes of oral contraceptive users towards their availability without a prescription in the Republic of Ireland. AB - BACKGROUND: Previous studies show that provision of oral contraceptive pill (OCs) without a prescription is safe, feasible and effective and that users are interested in obtaining contraception in this way, especially if a pharmacist screening is involved. A recent national survey conducted in the Republic of Ireland has highlighted that unintended pregnancy resulting from the failure of OCs could be linked to poor compliance due to costs and difficulty of access. OBJECTIVE: To evaluate views and attitudes of OC users towards the availability of OCs without a prescription in the Republic of Ireland. METHODS: A cross sectional survey was conducted using an opportunistic sample of OC users aged 18 to 50 years. Sixty community pharmacists were recruited nationwide. Data were collected using self-completed questionnaires. The questionnaires comprised information on: demographic data, need of the service, views on the availability of OCs without prescription, advantages and concerns around the service, role of pharmacists and cost implications for private and public patients. RESULTS: A total of 488 eligible OC users completed the survey. The majority of the respondents (71.7%;n = 350/488) reported to have missed a pill for reasons connected to the OCs prescription status and 55.5% (n = 268/488) of the respondents reported to have felt distressed on at least one occasion because they could not renew their OC prescription. A total of 87.9% (n = 429/488) of the respondents said they were in favour of OCs being available without prescription and 92% (n = 448/488) said they were likely to obtain OCs without prescription if available. Convenience and ease of access were indicated as the main advantages of availing of OCs without prescription, while safety was the biggest concern reported. Over 88% (n = 430/488) of the respondents indicated that pharmacists would be able to safely supply OCs without prescription. Private patients expected to save an average of 27.3% on their OC if obtained without prescription. CONCLUSIONS: OC users in the Republic of Ireland are in favour of OCs being available without prescription and are willing to obtain it this way, providing that pharmacists supply them according to protocols that facilitate the safety and the efficacy of the supply. An easier and more convenient access to OCs could also reduce the likelihood of missed pills and bring considerable savings to users. PMID- 26131046 TI - Pattern of drug therapy problems and interventions in ambulatory patients receiving antiretroviral therapy in Nigeria. AB - OBJECTIVES: We describe the frequency and types of drug therapy problems (DTPs), and interventions carried out to resolve them, among a cohort of HIV-infected patients on ART in Jos, Nigeria. METHODS: A prospective pharmacists' intervention study was conducted between January and August 2012 at the outpatient HIV clinic of the Jos University Teaching Hospital (JUTH). Pharmacists identified DTPs and made recommendations to resolve them. The main outcome measures were number of DTPs encountered, interventions proposed and acceptance rate of recommendations. RESULTS: A total of 42,416 prescriptions were dispensed to 9339 patients during the eight months study. A total of 420 interventions (Intervention rate of 1 per 100 prescriptions) were made to resolve DTPs in 401 (4.3%) patients with a mean age of 41 (SD=10) years, and made up of 73% females. DTPs encountered were drug omission (n=89, 21.2%), unnecessary drug (n=55, 13.1%) and wrong drug indication (n=55, 13.1%). Recommendations offered included; Addition of another drug to the therapy (n=87, 20.7%), rectification of incomplete prescriptions (n=85, 20.2%), change of drug or dosage (n=67, 16.0%), and discontinuation of the offending drug (n=59, 14.0%). A total of 389 (93%) out of 420 of the recommendations were accepted. In all, 50.4% (212) of the problematic prescriptions were changed and dispensed, 22.2% (89) were clarified and dispensed, while wrong identities were corrected in 11.7% (49). However, 7.5% (30) prescriptions were dispensed as prescribed, 5.2% (21) were not dispensed, and 3% (12) were unresolved. CONCLUSION: Our findings suggest that pharmacists-initiated interventions can ameliorate DTPs in patients receiving ART given the high intervention acceptance rate recorded. The implication of this finding is that pharmacists with requisite training in HIV pharmacotherapy are an excellent resource in detecting and minimizing the effect of antiretroviral drug-related errors. PMID- 26131047 TI - A pharmacist-led follow-up program for patients with established coronary heart disease in North Norway - a randomized controlled trial. AB - OBJECTIVES: The aim of the study was twofold; 1) to develop a clinical pharmacist led 12 month lasting follow-up program for patients with established coronary heart disease (CHD) discharged from the University Hospital of North Norway, and 2) to explore the impact of the program with regards to adherence to a medication assessment tool for secondary prevention of CHD and change in biomedical risk factors. METHODS: A total of 102 patients aged 18-82 years were enrolled in a non blinded randomized controlled trial with an intervention group and a control group. The intervention comprised medication reconciliation, medication review and patient education during three meetings; at discharge, after three months and after twelve months. The control group received standard care from their general practitioner. Primary outcomes were adherence to clinical guideline recommendations concerning prescription, therapy goal achievement and lifestyle education defined in the medication assessment tool for secondary prevention of CHD (MAT-CHDSP). Secondary outcomes included changes in the biomedical risk factors cholesterol, blood pressure and blood glucose. RESULTS: Ninety-four patients completed the trial, 48 intervention group patients and 46 controls. Appropriate prescribing was high, but therapy goal achievement was low in both groups. Overall adherence to MAT-CHDSP criteria increased in both groups and was significantly higher in the intervention group at study end, 78.4% vs. 62.0%, p<0.001. The difference was statistically significant for the documented lifestyle advices in intervention group patients. No significant improvements in biomedical risk factors were observed in favor of the intervention group. CONCLUSIONS: The study showed an increased guideline adherence in both study groups. This indicates that attention to clinical practice guideline recommendations in itself increases adherence - which may be a clinical pharmacist task. A larger adequately powered study is needed to show a significant difference in biomedical risk factor improvements in favor of the intervention. Amendments to the follow-up program are suggested before implementation in standard patient care can be recommended. PMID- 26131048 TI - An overview of upcoming changes in pregnancy and lactation labeling information. AB - BACKGROUND: Many medications can be used safely and effectively to provide health benefits for disease state management during pregnancy with minimal risk to the fetus or mother. Today nine out of ten women take at least one medication during pregnancy, and the number of women taking four or more medications has more than doubled over the past 30 years. However, the lack of safety data combined with the generalizations of the current risk category system (A, B, C, D, X) makes risk versus benefit assessment difficult. DISCUSSION: In response to these concerns, the U.S. Food and Drug Administration (FDA) has decided to implement a new pregnancy and lactation labeling rule designed to improve risk versus benefit assessment of drugs used in pregnant and nursing mothers; this rule is set to take effect in June of 2015. This change is designed to provide clear and detailed information for both patients and healthcare providers pertaining to three main categories: pregnancy, lactation, and females and males of reproductive potential. The new labeling rule also removes the previous letter risk categorization system. CONCLUSION: The upcoming changes regarding pregnancy and lactation safety labeling are going to have a vast impact on drug safety interpretation and prescribing practices. While this rule will provide practitioners with more detailed information pertaining to pregnancy, lactation, and reproduction, it will also place more responsibility on the practitioners to ensure the safety of their patients. This review will summarize these changes and discuss their potential effect on clinical practice. PMID- 26131049 TI - Acoustic radiation force impulse elastography for differentiation of malignant and benign breast lesions: a meta-analysis. AB - This meta-analysis was aimed to assess the diagnostic performance of acoustic radiation force impulse (ARFI) elastography for the differentiation of malignant and benign breast lesions. The databases of PubMed, Web of Science(TM), WanFang, Vip, SinoMed and China National Knowledge Infrastructure were searched for all studies that evaluated the diagnostic performance of ARFI including virtual touch tissue quantification (VTQ) and virtual touch tissue imaging (VTI). All the studies were published prior to Mar. 21, 2014. The studies published in English or Chinese were collected. A total of 11 studies, including 1,408 breast lesions from 1,245 women, were analyzed. The values of summary sensitivity and summary specificity were 0.843 (95% confidence interval [CI]: 0.811-0.872) and 0.932 (95% CI: 0.913-0.948) for VTQ of ARFI, and 0.864 (95% CI: 0.799-0.914) and 0.882 (95% CI: 0.832-0.922) for VTI of ARFI, respectively. Subgroup analysis excluding mucinous carcinoma and carcinoma in situ showed higher summary sensitivity (0.877 95% CI: 0.835-0.911), higher summary specificity (0.943 95% CI: 0.921-0.960) and lower heterogeneity (I(2)=23.5%). The cut-off values for shear wave velocity of VTQ ranged widely from 2.89 to 6.71 m/s, while the VTI ranged narrowly from 1.37 to 1.66. In general, ARFI elastography seems to be a good method for differentiation between benign and malignant breast lesions. However, its usefulness for identifying breast mucinous carcinoma and breast carcinoma in situ is limited. VTI seems to be more reliable and repeatable than VTQ. PMID- 26131050 TI - P15 gene methylation in hepatocellular carcinomas: a systematic review and meta analysis. AB - OBJECTIVE: This study was performed to investigate the correlation between P15 methylation and hepatocellular carcinoma (HCC) and hepatocirrhosis using a meta analysis of available case control studies. METHODS: Previous studies have primarily evaluated the incidence of P15 methylation in HCC and corresponding control groups, and compared the incidence of P15 methylation in liver cirrhosis and control groups. Data regarding publication information, study characteristics, and incidence of P15 methylation in both groups were collected from these studies and summarized. RESULTS: Ten studies that assessed P15 gene methylation in 824 HCC tumour tissues and five studies analyzing P15 methylation in 155 liver cirrhosis tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P15 methylation was significantly higher in HCCs than in adjacent non-tumour tissues (OR 9.04, 95% CI 5.80-14.09, P < 0.00001). Moreover, P15 methylation was significantly higher in liver cirrhosis tissues than in control tissues (OR 7.82, 95% CI 3.58-17.07, P < 0.00001). CONCLUSIONS: we found that P15 methylation was associated with an increased risk of HCC and liver cirrhosis. P15 hypermethylation induced the inactivation of the P15 gene, which played an important role in hepatocarcinogenesis. PMID- 26131051 TI - Prognostic and clinicopathological significance of MACC1 expression in hepatocellular carcinoma patients: a meta-analysis. AB - OBJECTIVE: Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies. However, the prognostic and clinicopathological value of MACC1 in hepatocellular carcinoma (HCC) remains inconclusive. Therefore, we conducted this meta-analysis to investigate the association between MACC1 expression and the outcomes of HCC. METHODS: Relevant articles were searched in PubMed, Embase, Sciencedirect, CNKI, and Wanfang databases updated to October 2014. The pooled hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were assessed using STATA 10.0, and then the correlations of MACC1 expression with overall survival (OS), disease free survival (DFS), and clinicopathological features were analyzed. RESULTS: 9 studies with a total of 1293 HCC patients were included in this meta-analysis. Our results showed that MACC1 over-expression was significantly associated with poor OS (HR = 2.30, 95% CI 1.47-3.59, univariate analysis; HR = 2.39, 95% CI 1.49 3.82, multivariate analysis), poor DFS (HR = 1.73, 95% CI 1.40-2.13, univariate analysis). Moreover, MACC1 over-expression was significantly associated with AFP level (OR = 1.31, 95% CI 1.03-1.68), tumor number (OR = 1.37, 95% CI 1.07-1.75), differentiation (OR = 2.37, 95% CI 1.46-3.83), TNM stage (OR = 2.89, 95% CI 2.18 3.82), vascular invasion (OR = 1.89, 95% CI 1.43-2.50), capsule invasion (OR = 2.89, 95% CI 1.40-5.94), and metastasis (OR = 2.66, 95% CI 1.16-6.10). CONCLUSION: MACC1 over-expression indicated poor survival rate, high recurrence rate, and aggressive biological behaviors. MACC1 can serve as an indicator of prognosis and a potential novel target for treatment in HCC patients. PMID- 26131052 TI - A systematic review of the identification of seniors at risk (ISAR) tool for the prediction of adverse outcome in elderly patients seen in the emergency department. AB - The purpose of this systematic review was to evaluate the predictive validity of the Identification of Seniors at Risk (ISAR) Tool in identifying elderly patients at risk of adverse outcomes after a visit to the emergency department (ED). Since older adults are frequently sent to the ED, screening for risk of adverse outcomes in elderly patients is increasingly important in the ED. Also it is a way to ensure that interventions based on a comprehensive geriatric assessment (CGA) are provided to patients identified at risk to reduce the risk of adverse outcomes. The ISAR is a six-item risk-screening tool for elderly patients seen in the ED. However the predictive validity of ISAR is controversial. Relevant studies from January 1999 through December 2014 were searched systematically in PubMed, Cochrane Library, Web of Knowledge, Scopus, CINAHL, Elsevier ScienceDirect databases. The language was restricted to English. This review was based on the recommendations of the Cochrane Handbook of Diagnostic Test Accuracy Reviews. Ten studies (8680 patients) were included in this review. With a cutoff score at least 2, the ISAR was proved to have poor validity related to revisiting the ED (AUC: 0.59-0.60) and hospital readmission (AUC: 0.59-0.60). The predictive validity of the ISAR related to mortality and composite outcomes was graded as poor to fair. It is not suitable to use the ISAR alone for identifying seniors at risk for adverse outcomes in the ED. PMID- 26131053 TI - The NLRP3 inflammasome and stroke. AB - Inflammasome pattern recognition receptors, which belong to the family of multi meric proteins, play an important role in innate immunity, including NLRPs, NLRC, and NAIP. Among these receptors, NLRP3 (nucleotide-binding domain (NOD)-like receptor protein 3) inflammasome may activate the inflammation and participate in atherosclerosis, pathophysiology of myocardial infarction, resultin ischemia/reperfusion injury and stroke and other cardiovascular diseases. Effective regulation of NLRP3 may help prevent or even treat stroke. In recent years, the role of inflammation in stroke has attracted much attention, and the in-depth study of its mechanism of action is gradually clear. This mini-review focuses on the association of regulatory mechanisms of NLRP3 inflammasome with the development of stroke, which may supply some clues for future therapies and novel drug targets for stroke. PMID- 26131054 TI - The role of MTDH/AEG-1 in the progression of cancer. AB - Cancer progression is driven by an accumulation of numerous genetic and epigenetic alterations in cancer cells themselves as well as constructional changes in their microenvironment. Metadherin (MTDH)/Astrocyte elevated gene-1 (AEG-1) has emerged in recent years as a key contributor to the carcinogenic process in diverse organs and tissues. As a multifunctional mediator of carcinogenesis, MTDH/AEG-1 has been found to be involved in multiple signaling pathways, such as: PI3K/Akt, NF-kappaB, Wnt/beta-catenin and MAPK. Overexpression of MTDH/AEG-1 is observed in a variety of cancers belonging to all biological systems, and has crucial relevance with cancer progression, including initiation, proliferation, invasion, metastasis and chemoresistance. In addition, a plethora of studies have convincingly demonstrated that MTDH/AEG-1 overexpression markedly correlates with poor clinical prognosis. These findings suggest that MTDH/AEG-1 may be used as a potential biomarker for the diagnosis of cancer, monitoring of cancer progression, and target therapies which may simultaneously inhibit tumor growth, block metastasis, and intensify the efficacy of chemotherapeutic treatments. PMID- 26131056 TI - Serum glycated albumin is superior to hemoglobin A1c for correlating with HMGB1 in coronary artery disease with type 2 diabetic mellitus patients. AB - High mobility group box 1 protein (HMGB1) was significantly increased in coronary artery disease (CAD) with type 2 diabetic mellitus (T2DM) patients. This study was to investigate the relationship between average blood glucose level and HMGB1 level in CAD with T2DM patients. 164 CAD patients were divided into two groups: CAD with T2DM patients group and CAD without T2DM patients group. Glycated albumin (GA) and glycosylated hemoglobin A1c (HbA1c) and HMGB1 concentrations were measured in CAD with T2DM patients. The fasting glucose levels, GA and HbA1c levels were sinificantly increased in CAD with T2DM patients compared to those in CAD without T2DM patients (all P<0.05). The hs-CRP levels in CAD with T2DM patients were significantly higher than those in CAD without T2DM patients (P<0.05). The HMGB1 levels in CAD with T2DM patients were also significantly higher than those in CAD without T2DM patients (P<0.05). Both serum GA levels and HbA1c levels were positively correlated with HMGB1 levels (n=84, r=0.512 and r=0.402, both P<0.05). The present study showed that both serum GA levels and HbA1c levels were positively related with HMGB1 levels in CAD with T2DM patients. Increased blood glucose levels may contribute to the increased HMGB1 levels. GA level is superior to HbA1c level for correlating with HMGB1 level. PMID- 26131055 TI - Roles of sigma-1 receptors in Alzheimer's disease. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of senile dementia all over the world. Still no existing drugs can effectively reverse the cognitive impairment. However, Sigma-1 (sigma-1) receptors have been long implicated in multiple neurological and psychiatric conditions over these years. In this review, we discuss the current understanding of sigma-1 receptor functions. Through regulation of lipid rafts, secretases, kinases, neuroceptors and ion channels, sigma-1 receptors can influence cellular signal transduction, TCA cycle, oxidative stress, neuron plasticity and neurotransmitter release etc. Based on this, we suggest the key cellular mechanisms linking sigma-1 receptor to Alzheimer's disease. Besides, we detail the evidences showing that sigma-1 receptors agonists, being the promising compounds for treatment of cognitive dysfunction, exhibit robust neuroprotection and anti-amnesia effect against Abeta neurotoxicity in the progress of Alzheimer's disease. The evidence comes from animal models, preclinical studies in humans and full clinical trials. In addition, the questions to be solved regarding this receptor are also presented. When concerned with NMDAR, sigma-1 receptor activation may result in two totally different influences on AD. Utilization of sigma-1 agents early in AD remains an overlooked therapeutic opportunity. This article may pave the way for further studies about sigma-1 receptor on Alzheimer's disease. PMID- 26131057 TI - Displacement of a dental implant into the maxillary sinus after internal sinus floor elevation: report of a case and review of literature. AB - BACKGROUND: Dental implant placement in the posterior maxilla may be complicated by implant migration into the maxillary sinus. PURPOSE: To report the clinical and radiological characteristics of a patient who experienced dental implant displacement into the maxillary sinus following sinus floor elevation, and to compare our findings with those of other published reports of the displacement of dental implants. MATERIALS AND METHODS: Implant placement and maxillary sinus elevation were performed simultaneously. The location of the displaced implant was monitored for 8 years, until the ectopic implant was surgically removed using the lateral window approach. The contributing factors, treatment modality, and clinical outcome for our patient were compared with those of patients reported in the literature. RESULTS: The clinical characteristics of our case were similar to those of patients with displaced implants who were also asymptomatic for long periods. The clinical outcome of our case was consistent with that of patients who underwent similar surgeries. CONCLUSIONS: Transnasal endoscopic removal of an ectopic implant may be suitable in cases in which the ectopic implant is accessible. Transoral direct approaches are adequate in most cases in which endoscopic approaches may be confounded. The bony-window transoral technique may allow the removal of large implants. PMID- 26131058 TI - Correlation between anatomical parameters of intertubercular sulcus and retroversion angle of humeral head. AB - OBJECTIVE: To obtain anatomical data on intertubercular sulcus of humerus, evaluate the correlation between intertubercular sulcus and retroversion angle of humeral head, to guide the positioning of torsion angle of prosthesis during total shoulder arthroplasty and provide references for shoulder prosthesis design. METHODS: Using a Siemens Ultrahigh speed 64- rows multi-slices spiral CT scanner and 20 dried adult humeral specimens (intact specimen, no fractures or pathological damage), of these, left lateral in 10 cases, right lateral in 10 cases, male or female all inclusive, specimens are all provided by Anatomy Department of Weifang Medical College, scan ranged from the highest point of humeral head to the distal ends of trochlea. And scanned data were subjected to statistical analysis. RESULTS: There is a linear correlation between the distance from intertubercular sulcus to central axis line of humeral head, position angle of intertubercular sulcus and retroversion angle of humeral head at the beginning slice of intertubercular sulcus. There is a linear correlation between position angle of intertubercular sulcus and retroversion angle of humeral head at the slice of surgical neck. CONCLUSION: There is a linear correlation between position of intertubercular sulcus and retroversion angle of humeral head, in total shoulder arthroplasty, using intertubercular sulcus as anatomical landmark will help to accurately position torsion angle of individualized prosthesis. Position angle of intertubercular sulcus is an objective, flexible positioning indicator. PMID- 26131059 TI - Effectiveness and risk associated with infliximab alone and in combination with immunosuppressors for Crohn's disease: a systematic review and meta-analysis. AB - OBJECTIVE: Infliximab (IFX) monotherapy and IFX combined with immunosuppressors have been used in the treatment of Crohn's disease. However, the differences between combination therapy and IFX alone remain controversial. The aim of this meta-analysis was to evaluate the effectiveness and risk associated with combination therapy and IFX monotherapy. METHODS: Systematic searches were performed for randomized controlled trials with PubMed, Web of Science, OVID, and the Cochrane Library. The analyzed contents included induction of remission, short-term maintenance of remission, long-term maintenance of remission, and risks. The final results were estimated using statistical data of odds ratio (OR), relevant 95% confidence interval (CI), and P value. RESULTS: 6 out of 1041 citations met the selection criteria. There was no statistical difference in the effectiveness of induction and long-term maintenance of remission between two groups (P=0.07, 0.12). However, for short-term maintenance of remission, there was mild statistical difference between two groups (P=0.02, OR=1.66). For risks, apart from the difference in the aspect of reaction to infusion (OR=0.43, 95% CI=0.29-0.65, P<0.0001), there was no statistical difference. CONCLUSIONS: There was no significant difference in effectiveness and risks between the therapy groups. However, these outcomes should be interpreted with caution. Specific categories of combination therapy and periodic medication should be paid more attention in future studies. PMID- 26131060 TI - Lateral tarsal artery flap: an option for hypopharyngeal reconstruction in patients with hypopharyngeal carcinomas after surgery. AB - BACKGROUND: Hypopharyngeal reconstruction following resection of hypopharyngeal carcinoma has utilized local, regional and free tissue transfer flap options. No single surgical technique is currently in use for hypopharyngeal reconstruction that is applicable to all patients. In this article, we introduce the application of the lateral tarsal artery flap (LTA flap) as a reconstructive option following hypopharyngeal oncologic ablation. METHODS: From June 2010 to January 2012, four patients of hypopharyngeal carcinomas underwent total laryngectomy and partial pharyngectomy followed by single-stage reconstruction with LTA flaps. After operation, patients were treated with radical radiotherapy within four weeks. All the patients were followed up. RESULTS: All flaps survived, with an average size of 7.5 cm * 5.8 cm (range of 8.0-7.0 cm * 6.0-5.0 cm). There were no complications or contractures during the follow-up. Normal diets were adopted two weeks after operation. The follow-up ranged from 12-20 months (mean: 15 months). There were no distal stenosis or pharyngocutaneous fistula nor were there any donor-site complications. CONCLUSION: The LTA flap could be a viable option for hypopharyngeal reconstruction following head and neck oncologic resection. It seems that LTA flap would be a promising flap deserving extensively research. PMID- 26131061 TI - Gene microarray analysis of lncRNA and mRNA expression profiles in patients with hypopharyngeal squamous cell carcinoma. AB - BACKGROUND: Studies have shown that long noncoding RNAs (lncRNAs) are involved in the development and progression of many types of cancer. However, the mechanisms by which lncRNAs influence development and progression of hypopharyngeal squamous cell carcinoma (HSCC) are unclear. METHOD: We investigated differences in lncRNA and mRNA expression profiles between 3 pairs of HSCC tissues and adjacent nontumor tissues by microarray analysis. RESULTS: In HSCC tissues, 1299 lncRNAs were significantly upregulated (n=669) or downregulated (n=630) compared to levels in adjacent nontumor tissues. Moreover, 1432 mRNAs were significantly upregulated (n=684) or downregulated (n=748) in HSCC tissues. We randomly selected 2 differentially expressed lncRNAs (AB209630, AB019562) and 2 differentially expressed mRNAs (SPP1, TJP2) for confirmation of microarray results using qRT-PCR. The qRT-PCR results matched well with the microarray data. The differentially expressed lncRNAs and mRNAs were distributed on each of the chromosomes, including the X and Y chromosomes. Pathway analysis indicated that the biological functions of differentially expressed mRNAs were related to 48 cellular pathways that may be associated with HSCC development. GO analysis revealed that 593 mRNAs involved in biological processes, 50 mRNAs involved in cellular components, and 46 mRNAs involved in molecular functions were upregulated in the carcinomas; 280 mRNAs involved in biological processes, 58 mRNAs involved in cellular components, and 71 mRNAs involved in molecular functions were downregulated in the carcinomas. In addition, 8 enhancer-like lncRNAs and 21 intergenic lncRNAs with their adjacent mRNA pairs were identified as coregulated transcripts. CONCLUSION: These findings provide insight into the mechanisms underlying HSCC tumorigenesis and will facilitate identification of new therapeutic targets and diagnostic biomarkers for this disease. PMID- 26131062 TI - Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence. AB - BACKGROUND: There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. METHODS: All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. RESULTS: The mRNA expressions of adenoma carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. CONCLUSION: The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma. PMID- 26131063 TI - Bone fracture and the interaction between bisphosphonates and proton pump inhibitors: a meta-analysis. AB - OBJECTIVE: Recent studies suggested an increased risk of fractures with interaction between bisphosphonates (BPs) and proton pump inhibitors (PPIs). We performed a meta-analysis of fractures between patients taking BPs/PPIs and those taking BPs only. METHODS: We conducted a PubMed database and Ovid database search, as well as Cochrane Library search (up to July 2014) for studies assessing the association between fractures and BPs or/and PPIs. We performed random effects meta-analysis of odds ratios (OR) according to fracture type and conducted subgroup analyses by race and BP subtypes. Heterogeneity was assessed using Q statistics and I(2) statistic. RESULTS: After study selection, 4 unique studies (5 comparisons) including 57259 patients were available for this meta analysis. Pooled analysis of overall fracture risk of BP+PPI group versus BP group showed a significant increase in risk of fractures (OR = 1.52, P = 0.025), with substantial heterogeneity. However, heterogeneity was drastically reduced in subgroup of Asian (I(2) = 24% and P = 0.251), and fracture risk showed a significant increase (OR = 1.75, P = 0.026). In contrast, heterogeneity was little eliminated in subgroup of European, and fracture risk was no statistical difference (OR = 1.42, P = 0.068). Three studies including 4 comparisons reported on spine fracture were included in the pooled analysis demonstrating an increased spine fracture risk associated with BP/PPI interaction (OR = 1.60, 95% CI 1.13 2.26, P = 0.008, I(2) = 58.6%). CONCLUSIONS: This meta-analysis suggests that there is an interaction associated with increased fracture risk (particularly for spine and Asian race) between BP and PPI use. Clinicians should carefully evaluate such risk factors for osteoporosis in patients taking BPs, before routinely prescribing PPIs, and make a careful judgment as to whether PPIs may be safe for patients at high risk of fractures. PMID- 26131065 TI - An updated meta-analysis of laparoscopic versus open pyeloplasty for ureteropelvic junction obstruction in children. AB - PURPOSE: To further explore the feasibility and safety of laparoscopic pyeloplasty (LP) in children with ureteropelvic junction obstruction compared with open pyeloplasty (OP). METHODS: PUBMED, Web of science and Cochrane library were searched until Oct. 2014 to find eligible studies. WMD, OR, RD and their 95% CIs were used to estimate the difference. Baseline such as age, gender and crossing vessel, perioperative outcomes such as length of stay, operative time, overall complications, and success rate were compared. All the meta-analyses were performed in Revman 5.2. RESULTS: 15 comparative studies and one RCT were eligible and included in the meta-analysis. Compared with OP, LP groups might be associated with shorted length of hospital stay (WMD: -1.92, 95% CI: -2.45- 1.39), reduced complications (OR: 0.71, 95% CI: 0.49-1.01) and equal success rate (RD: 0.01, 95% CI: -0.02-0.04), but prolonged operative time (WMD: 48.64, 95% CI: 31.16-66.12). CONCLUSION: Our findings supported that laparoscopic pyeloplasty is feasibility and safety in the treatment of UPJ obstruction in children, especially in high-volume centers with experienced experts. Considering the select bias and recall bias, more RCTs are required to further explore the efficiencies of LP. PMID- 26131064 TI - N-acetylcysteine protects Chinese Hamster ovary cells from oxidative injury and apoptosis induced by microcystin-LR. AB - This study aimed to investigate the MC-LR induced oxidative injury and apoptosis in Chinese hamster ovary (CHO) cells, and the protective effects of N acetylcysteine (NAC) on these cells. Cell viability was determined by MTT assay after exposure to NAC at various concentrations (0, 1, 5, 10, 20, 30, 40, 50, 60 and 80 mmol/L) alone, or NAC (0, 1 and 5 mmol/L) plus MC-LR (0, 2.5, 5 and 10 MUg/ml) for 24 h. The reactive oxygen species (ROS) in CHO cells were measured by DCFH-DA, mitochondrial membrane potential (MMP) by fluorescence probe JC-1 staining, and apoptosis index determined by Annexin V-PI staining. Results showed, following exposure to NAC alone for 24 h, cell viability remains higher than 80% at 1 and 5 mmol/L. After exposure to NAC at different concentrations plus MC-LR, cell viability increased, ROS decreased, MMP elevated, and apoptosis index reduced to a certain extent. In conclusion, MC-LR may induce the apoptosis of CHO cells by inducing ROS production which is protected by NAC. PMID- 26131066 TI - Clinical outcomes of Doppler-guided haemorrhoidal artery ligation: a meta analysis. AB - BACKGROUND AND OBJECTIVES: Numerous clinical studies have evaluated the potential benefits of DGHL for symptomatic hemorrhoids, particularly with regard to the perioperative parameters. However, the exact value of Doppler-assisted localization of vessels in hemorrhoid operations is still not clear. The aim of this study is to systematically analyze the randomized controlled trials on the effectiveness of DGHL and HL without Doppler guidance or other procedures for HD by using the principles of meta-analysis. MATERIALS AND METHODS: Relevant RCTs which assessed DGHL as the primary procedure and reported clinical outcomes as primary end-points were selected from Pubmed database, Embase database and the Cochrane library. Mean difference (MD) was used to represent effect-quantity for continuous variable results, while Odds ratio (RR) was used to represent effect quantity for discontinuous variable results. Statistical analysis was performed by RevMan 5.0 and STATA 12.0 software. RESULTS: Five RCTs with a total of 388 patients were analyzed systematically. The main results showed that DGHL and HL without Doppler guidance or other procedures are equally effective in terms of treatment success rate (RR = 0.89, 95% CI 0.73-1.09, P = 0.27), operation time (MD = 11.41, 95% CI -9.26-32.09, P = 0.28), postoperative complications (RR = 0.89, 95% CI 0.62-1.28, P = 0.53), postoperative pain (MD = -1.01, 95% CI -2.27 0.26, P = 0.12) and incidence of HD recurrence (RR = 1.07, 95% CI 0.83-1.39, P = 0.60). CONCLUSION: Our findings suggest that DGHL may not have evident superiority for the management of HD in terms treatment success rate, operation time, postoperative complications, postoperative pain and incidence of HD recurrence. However, further large scale randomized and multicentre studies are needed to confirm these findings. PMID- 26131067 TI - Local delivery of rhVEGF165 through biocoated nHA/coral block grafts in critical sized dog mandible defects: a histological study at the early stages of bone healing. AB - Alveolar defects of a critical size cannot heal completely without grafting. Thus, they represent a major clinical challenge to reconstructive surgery. Numerous types of grafts have been used to improve bone regeneration. In the case of particle grafts, the capacity for volume rebuilding and space maintaining is still not ideal, particularly for critical-sized bone defects. Although porous block grafts can overcome the above problems of particle grafts, they are still not widely used for critical-sized alveolar defects, because of their reduced efficacy in blood vessel and bone formation. Thus, in the present study, nano hydroxyapatite/coralline (nHA/coral) blocks were pre-vascularized by coating them with vascular endothelial growth factor (VEGF), and then implanted in dogs with critical-sized mandibular defects. This model has possible applications in orthopedic and implant surgery. In vivo results indicate that the nHA/coral blocks allow cell and collagen ingrowth because of their suitable pore size and interconnectivity of pores. In addition, pre-vascularization properties were obtained by coating the scaffolds with VEGF. Histological and immunohistochemical examinations, as well as fluorescence analysis, revealed that the local delivery of VEGF can significantly improve neovascularization and mineralization of newly formed bone at the early stages of bone healing in this dog implantation model. Our data collectively show that nHA/coral blocks have possible applications in bone tissue engineering, and excellent results can be achieved by pre vascularization with VEGF. PMID- 26131068 TI - Efficacy of growth hormone supplementation with gonadotrophins in vitro fertilization for poor ovarian responders: an updated meta-analysis. AB - Growth hormone (GH) is involved in the regulation of male and female infertility. Several clinical studies reveal that adjuvant GH treatment has a possible role in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), especially in poor ovarian responders (POR) undergoing IVF/ICSI. Recent studies suggest that GH addition in POR patients significantly improves the rate of clinical pregnancy and live birth. Databases including PubMed, Embase, the Cochrane Central China National Knowledge Infrastructure (CNKI) and Google Scholar were searched for randomized controlled trials (RCTs) or controlled clinical trials (CCTs) on the effectiveness of GH supplementation with gonadotrophins in IVF/ICSI for POR. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Meta Analyst Beta 3.13 software was used to meta-analysis. Eleven studies (six RCTs and five CCTs) and 3788 subjects (613 subjects in cases group and 3175 subjects in controls group) were included in our study. The results of meta-analysis showed that GH addition significantly increased serum E2 level on the day of HCG (OR = 0.55; 95% CI = 0.127-0.973) and MII oocyte number (OR = 0.827; 95% CI = 0.470-1.184). Furthermore, GH addition significantly improved the number of 2PN (OR = 0.934; 95% CI = 0.206-1.661) and obtained embryos (OR = 0.934; 95% CI = 0.206-1.661). However, no significant difference was found for the overall implantation rate was 8.8% (95% CI = -0.062-0.237) and clinical pregnancy rate was 5.1% (95% CI = -0.033-0.134). The present result revel that GH supplementation for IVF/ICSI in POR increases the probability of serum E2 level on the day of HCG, the number of MII oocyte, 2PN and obtained embryos. However, GH addition does not increase implantation rate and clinical pregnancy rates. Due to the limited quantity and quality of the included studies as well as the difference in methodology, we suggest this above could be taken as a reference for clinical analysis which needs to be further evaluated in its effects. PMID- 26131069 TI - The influence of cardiac autonomic nerve plexus on the electrophysiological properties in canines with atrial fibrillation. AB - BACKGROUND: This study sought to examine the effect of the cardiac autonomic nerve plexus, which originates from the vagus nerve trunk, on atrial vulnerability. METHODS: Dogs in group I (n = 6) underwent ganglionated plexi (GP) sequential ablation following six hours of left atrial appendage rapid atrial pacing (RAP). The monophasic action potential duration at 90% of repolarization (APD90), effective refractory period (ERP), and the atrial fibrillation inducing rate of bilateral atria and pulmonary veins were recorded at baseline, l h, 3 h and 6 h after pacing, as well as after sequential ablation (RAGP + RIGP ablation, LSGP + RIGP ablation). Dogs in group II (n = 6) received vagus nerve stimulation following six hours of left atrial appendage RAP. APD90, ERP and atrial fibrillation inducing rate of bilateral atria and pulmonary veins were recorded at baseline, 1 h, 3 h and 6 h after pacing, as well as after GP sequential ablation (RAGP + RIGP ablation, LSGP + RIGP ablation). RESULTS: In group I, APD90 and ERP progressively shortened and atrial fibrillation inducing rate increased in various sites l h, 3 h and 6 h after RAP (P < 0.05). APD90 and ERP shortened significantly and atrial fibrillation inducing rate was significantly higher in the left atrial appendage and bilateral pulmonary veins than in other sites (P < 0.05). Following GP sequential ablation, APD90, ERP and atrial fibrillation inducing rate were not significantly different from baseline levels (P > 0.05). In group II, APD90 and ERP progressively shortened in various sites over pacing time period, and the atrial fibrillation inducing rate increased l h, 3 h and 6 h after RAP + VNS (P < 0.05). APD90 and ERP shortened significantly and atrial fibrillation inducing rate was significantly higher in the left atrial appendage and right superior/inferior pulmonary veins when compared with other sites (P < 0.05). After GP sequential ablation, APD90, ERP and atrial fibrillation inducing rate were not significantly different from baseline levels (P > 0.05). Compared with group I, APD90 and ERP shortened significantly, while atrial fibrillation inducibility increased significantly at baseline and l h, 3 h, and 6 h after pacing in group II (P < 0.05). After ablation of the four major cardiac GPs, no significant differences were observed in the two groups with respect to APD90, ERP and atrial fibrillation inducing rate (P > 0.05). CONCLUSION: GP activation, as a result of vagal nerve stimulation, alters MAP90, ERP and atrial fibrillation inducing rate of the atrium and pulmonary veins and promotes the occurrence of RAF in the early stage of atrial fibrillation, resulting in increased atrial vulnerability and triggering the occurrence and maintenance of atrial fibrillation. PMID- 26131070 TI - Therapeutic efficacy of paclitaxel and carboplatin via arterial or venous perfusion in rabbits with VX-2 tongue cancer. AB - OBJECTIVE: This study aimed to investigate the therapeutic efficacy of paclitaxel in combination with carboplatin in different ways in rabbits with VX-2 tongue cancer. METHODS: Rabbit VX-2 tongue cancer model was established and animals were then divided into 6 groups, in which animals received perfusion with paclitaxel liposome and carboplatin via the lingual artery, with free paclitaxel and carboplatin via the lingual artery, with 5% glucose via the lingual artery, with paclitaxel liposome and carboplatin via ear vein, with free paclitaxel and carboplatin via the ear vein and with 5% glucose via the ear vein independently. When the maximum diameter of cervical lymph nodes was larger than 5 mm, chemotherapy was initiated. Seven days later, flow cytometry and immunohistochemistry were performed to detect the apoptosis of VX-2 cells and P53 expression in the primary cancer and metastatic lymph nodes. RESULTS: Targeted arterial perfusion with paclitaxel liposome in combination with carboplatin was more effective to induce the apoptosis of cancer cells in the primary cancer and metastatic lymph nodes and inhibit their proliferation. CONCLUSION: Targeted arterial perfusion with paclitaxel liposome in combination with carboplatin is effective to reduce tumor size, attenuate the surgery induced injury and improve the post-operative quality of life of oral cancer patients. PMID- 26131071 TI - The ability to form cartilage of NPMSC and BMSC in SD rats. AB - OBJECTIVE: In this study, we observed the difference in the ability of cartilage differentiation between nucleus pulposus mesenchymal stem cells (NPMSC) and bone marrow mesenchymal stem cells (BMSC). METHODS: NPMSC and BMSC were isolated from SD rats. Their proliferation abilities were detected by CCK-8 methods, their multilineage differentiation abilities were observed using Alizarin red staining, oil red O staining and Alcian Blue staining methods. The expression levels of osteogenic, adipogenic, chondrogenic genes were detected with RT-PCR and Western blotting methods. RESULTS: There was no obvious difference in the proliferation ability between NPMSC and BMSC cells. NPMSC and BMSC cells expressed stem cell genes and the surface markers and showed osteogenic, adipogenic and chondrogenic multi-directional differentiation capability of cartilage under induction in vitro. CONCLUSIONS: We confirmed that NPMSC with characteristics of stem cells can be isolated and cultured from nucleus pulposus tissues of intervertebral disc of SD rats, the chondrogenic ability of NPMSC and BMSC was similar under induction in vitro. This could provide a new seed cells for tissue engineering. PMID- 26131072 TI - Apex radicis dentis excision operation guided by template made by CAD/CAM. AB - OBJECTIVE: The aim of the study is to explore the clinical efficacy of apex radicis dentis excision guided by a template made by Computer Aided Design/Computer Aided Manufacture (CAD/CAM). METHODS: Base on the CBCT image of oral cavity, a three-dimensional model of patient's oral cavity was built. Then the access way and excisional area were defined based on the model. Finally, the operative guide template was designed and made to help define the direction, depth, and area of the surgery. RESULTS: One year after the operation with guide template, the two cases of apex radicis dentis with difficulty in cure were proven to have normal masticatory function and their pathological changes of apex radicis dentis disappeared as well. CONCLUSION: Utilization of CAD/CAM technology could well design the operative guide template for the resection of apex radicis dentis. Usingthis guide template could make the excision of apex radicis dentis more quickly and safer. PMID- 26131073 TI - Analgesic effects of melatonin on post-herpetic neuralgia. AB - OBJECTIVE: This study aims to explore the analgesic effects of melatonin on post herpetic neuralgia and its possible mechanism. METHODS: A total of 48 PHN Wistar rats were divided into 4 groups randomly: Normal, PHN, PHN+MT and naloxone, 4P PDOT or L-arginine+120 mg/kg MT (C). Heat pain latency was determined after MT injection for 20 min, 40 min, 80 min and 120 min respectively. The expression levels of delta receptor and MT2 receptor in different tissues of rats were detected by RT-PCR method. NO content was determined. RESULTS: Heat pain latency in PHN rats were lower than that of control group (P<0.05), MT could increase the heat pain latency with dose-dependent, while naloxone, 4P-PDOT and L-arginine could reverse the analgesic effect of MT (P<0.05). The expression levels of delta receptor and MT2 receptor in spinal cord, hypothalamus and hippocampus in PHN+MT (120 mg/kg, i. p.) group were significantly higher than that of PHN group (P<0.05). The NO levels in the brain and spinal cord tissues in PHN group were higher than that of PHN+MT (120 mg/kg) group (P<0.05). CONCLUSIONS: MT had significant analgesic effects in the treatment of PHN, and its mechanism was closely related with deltaopioid receptor, NO and MT2 receptor. PMID- 26131074 TI - Expression profile of long non-coding RNAs is altered in endometrial cancer. AB - This study was to uncover the role of long non-coding RNA (lncRNA) in the process of endometrial cancer (EC) development using microarray technique to obtain the expression profiles of lncRNAs in EC and its adjacent normal tissues. A total of 45 pieces of pathologically-proven EC tissues were used in this study. All samples were frozen in liquid nitrogen immediately after resection and stored at 80 degrees C for future use. The detection of lncRNA and transcripts was conducted using microarray analysis. To understand the biochemical function of lncRNA, bioinformatics analyses (gene ontology and pathway analyses) were performed. To further investigate the relationship between lncRNAs and EC, subgroup analysis was conducted. In order to validate the consistency of the lncRNAs with microarray data, qRT-PCR was performed. In this study, 30586 lncRNAs and 26109 transcripts (fold change >= 2.0) were found in the tested EC. In particular, compared with normal tissues, 4010 the lncRNA were up-regulated, and 3350 of them were down-regulated. Seven of the lncRNAs were in accordance with microarray data in qRT-PCR. Among these lncRNAs, 3 were up-regulated and 4 were down-regulated. Furthermore, pathway analysis revealed that 24 pathways were correlated to the up-regulated transcripts, while 27 pathways were associated with the down-regulated transcripts. Our study demonstrated that the expressions of a large amount of lncRNAs were altered in EC in comparison to normal tissues, suggesting that lncRNAs could potentially serve as a diagnostic biomarker that is beneficial for the diagnosis and therapy of EC. PMID- 26131075 TI - Cortex Mori Radicis Extract induces neurite outgrowth in PC12 cells activating ERK signaling pathway via inhibiting Ca(2+) influx. AB - Cortex Mori Radicis is a traditional Chinese herbal medicine which has a long history of use for the treatment of headaches, cough, edema and diabetes. However, its function and mode of action within nervous system remain largely unclear. In the present study, we have attempted to determine the effects of Cortex Mori Radicis Extract (CMRE) on neuronal differentiation. Here, we reported that CMRE induces the neurite outgrowth in pheochromocytoma PC12 cells and primary cortical neuron. Following the generation of neurite outgrowth, extracellular Ca(2+) influx was inhibited and intracellular Ca(2+) decreased. In addition, CMRE induced the extracellular signal-regulated kinase 1/2 (ERK1/2) activation and also stimulated the Rap1-GTP expression, which is closely linked to neuritogenesis. Moreover, the neurite outgrowth induced by CMRE was antagonized to a marked degree by suppressing activation of p-ERK1/2 with the specific ERK1/2 inhibitor (PD98059), suggesting the involvement of Rap1-GTP and ERK1/2 in CMRE-induced neurite outgrowth. Taken together, these results demonstrate that CMRE induces neurite outgrowth of PC12 cells through Rap1-ERK signaling pathway via inhibiting Ca(2+) influx, and provide a novel insight into the manner in which CMRE participates in neuritogenesis. PMID- 26131076 TI - Differential lncRNA expression profiles in recurrent gliomas compared with primary gliomas identified by microarray analysis. AB - Glioma, especially high-grade glioma, is highly malignant with high rate of recurrence and poor prognosis. The mechanisms of glioma progression and recurrence have not been elucidated. Previous studies showed that long non-coding RNAs (lncRNAs) involved in the development and progression of glioma. However, the roles of lncRNAs in the recurrence of glioma remain unknown. We use high throughput microarray to screen the differentially expressed lncRNAs and mRNAs in recurrence gliomas compared with primary gliomas. We found a total of 1,111 lncRNAs were differentially expressed in recurrent group. Among these, 639 lncRNAs were up-regulated, while 472 lncRNAs were down-regulated (fold Change >=2.0). GO (Gene ontology) and pathway analysis revealed that the potential functions of differentially expressed lncRNAs were closely connected with the processes of cancer progression and pathogenesis. LncRNA classification and subgroup analysis further identified three important clusters of differentially expressed lncRNA-mRNA pairs which have potential gene regulatory functions. This study for the first time showed abundant differentially expressed lncRNAs in recurrent gliomas. Some lncRNAs may play important roles in glioma recurrence, such as previously reported H19, CRNDE, HOTAIRM1 or unreported AC016745.3, XLOC_001711, RP11-128A17.1. Moreover, this study set a basis for future researches on specific lncRNA which may contribute to the recurrence of glioma. Further studies on these lncRNAs will help to elucidate the mechanism of glioma recurrence at genetic level and find therapeutic targets for glioma patients. PMID- 26131077 TI - Slightly focused high-energy shockwave therapy: a potential adjuvant treatment for osteoporotic fracture. AB - Slightly focused high-energy shockwave (HESW) therapy is characterized by a wide focal area, a large therapy zone, easy positioning and less pain during treatment. The objective of this study was to perform for the first time an in vivo test of the slightly focused HESWs for osteoporotic fractures. Bilateral proximal tibial osteotomies were made in 30 ovariectomized (OVX) Sprague-Dawley rats and secured with internal fixation. The osteotomy site in the left tibia was subsequently treated with slightly focused HESWs with the energy flux density of 0.26 mj/mm(2), shock repetition frequency of 1 Hz and 2000 shocks (OVX + HESW group). The contralateral right tibia was not treated and served as the control (OVX group). Roentgenographic examination 2, 4, 6, and 8 weeks after osteotomy showed that HESW treatment accelerated tibia fracture healing in osteoporotic rats. Histological examination 2, 4, and 8 weeks after HESW treatment showed a greater inflammatory reaction in the OVX + HESW group, with more mature collagen and trabeculae than in the OVX group. Micro computer tomography (Micro-CT) scanning after 4 and 8 weeks showed that bone volume (BV), bone volume/tissue volume (BV/TV), mean trabecular thickness (Tb.Th), and mean trabecular number (Tb.N) were about 45.0% and 33.1%, 18.4% and 20.1%, 38.2% and 20.9%, 26.7% and 28.4%, respectively, higher in the treatment group than in the control group (P < 0.05); and the mean trabecular separation (Tb.Sp) was about 16.7% and 27.3% lower in the treatment group (P < 0.05). Four and eight weeks after HESW treatment, the maximum compressive callus endurance was about 72.3% and 25.5%, respectively, higher in the treatment group than in the control group (P < 0.05). These results show that slightly focused HESW therapy has a beneficial effect on osteoporotic tibial fracture healing. Slightly focused HESWs could increase callus endurance, induce bone formation, and improve trabecular bone microarchitecture and biomechanical properties. PMID- 26131078 TI - The application of porous tantalum cylinder to the repair of comminuted bone defects: a study of rabbit firearm injuries. AB - The aim of this study is to investigate the effect of porous tantalum material in repair tibial defects caused by firearm injuries in a rabbit model. A multifunctional biological impact machine was used to establish a rabbit tibial defect model of firearm injury. Porous tantalum rods were processed into a hollow cylinder. Kirschner wires were used for intramedullary fixation. We compared the differences of the bone ingrowth of the porous tantalum material by gross observations, X-rays and histological evaluations. The radiographic observations revealed that fibrous tissue covered the material surface after 4 weeks, and periosteal reactions and new bone callus extending materials appeared after 8 weeks. After 16 weeks, the calluses of the firearm injury group were completely wrapped around a porous tantalum material. The group with the highest Lane-Sandhu X-rays cores was the firearm injury and tantalum implant group, and the blank control group exhibited the lowest scores. The histological evaluations revealed that the presence of new bone around the biomaterial had grown into the porous tantalum. By the 16th week, the areas of bone tissue of the firearm injury group was significant higher than that of non-firearm injury group (P<0.05). The comminuted fractures treated with tantalum cylinders exhibited greater bone ingrowth in the firearm injury group. In conditions of firearm injuries, the porous tantalum biomaterial exhibited bone ingrowth that was beneficial to the treatment of bone defects. PMID- 26131079 TI - Cardioprotective role of vitamin D receptor in circulating endothelial cells of ApoE-deficient mice. AB - Atherosclerosis is the key course of coronary heart disease. In this study, we investigated the effect of vitamin D receptor on serum 1,25-(OH)2D levels, lipid profiles, nitric oxide expression, apoptosis-related gene Bcl-2, fas protein levels, in ApoE-deficient mice. The proliferation activity of VDR-RNAi transfected endothelial cells was decreased, the ability of apoptosis was increased, nitric oxide concentration was decreased and eNOS protein level was significantly reduced. VDR-RNAi induced lipid metabolism abnormality, reduced eNOS and ApoE levels, promoted lipid peroxidation, damaged the endothelial function and accelerated the process of atheroscleros. Together, our data presented a novel role for VDR in the pathogenesis process of atheroscleros by up regulating eNOS protein expression which could lay a solid foundation of VDR specific activator treatment for coronary artery disease. PMID- 26131080 TI - Microarray analysis of anti-cancer effects of docosahexaenoic acid on human colon cancer model in nude mice. AB - Docosahexaenoic acid (DHA), a derivative of omega3- polyunsaturated fatty acids present in fish oil, is well known to have anticancer activity on colon cancer cells, but the molecular and cellular mechanisms remain to be further clarified. In this study, anti-cancer effects of DHA on colon cancer cells were observed in a nude mouse HCT-15 xenograft model. And then, the different genes expression and signal pathways involved in this process were screened and identified using cDNA microarray analysis. Results of genes expression profiles indicated a reprogramming pattern of previously known and unknown genes and transcription factors associated with the action of DHA on colon cancer cells. And several genes related to tumor growth and metastasis including COX2, HIF-1alpha, VEGF-A, COMP, MMP-1, MMP-9, SCP2, SDC3, which were down-regulated by DHA, were further confirmed in HCT-15 cell line using RT-PCR method. In summary, our data might provide novel information for anti-cancer mechanism of DHA in colon cancer model. PMID- 26131081 TI - Ultrasound findings of mild neonatal periventricular-intraventricular hemorrhage after different treatments. AB - OBJECTIVE: To investigate the ultrasound findings of mild neonatal periventricular-intraventricular hemorrhage (PIVH) after different treatments, and to evaluate the neurological outcomes of mild PIVH with Gesell Development Diagnosis Scale (GDDS). METHODS: A total of 194 newborns with grade I-II PIVH were recruited, and findings of cranial ultrasound examination before and 1 month after birth were included for analysis. The echo intensity and size of the lesions were recorded. RESULTS: There was no significant difference in the echo intensity among three groups of grade I PIVH patients (P>0.05). There was significant difference in the echo intensity among three groups of grade II PIVH patients, and the ganglioside had the best therapeutic efficacy (P<0.05). No significant difference was observed in the area change among three groups of grade I PIVH patients (P>0.05). However, significant difference was observed in the area change among three groups of grade II PIVH patients, and ganglioside had a better efficacy than cerebrolysin and control agent (P<0.05), but there was no significant difference between cerebrolysin and control groups (P>0.05). GDDS evaluation showed no significant difference among three groups (P>0.05), and all the patients recovered completely. CONCLUSION: The efficacy of different treatments for mild PIVH can be reflected in the ultrasound findings. Mild PIVH children generally have a good neurological prognosis. PMID- 26131082 TI - Intermittent low-level vagosympathetic nerve trunk stimulation inhibits ganglionated plexi activity to prevent atrial fibrillation. AB - BACKGROUND: The cardiac autonomic nervous system (CANS) plays a role in the occurrence and persistence of atrial fibrillation (AF). Low-level vagosympathetic nerve stimulation (LL-VNS) has been shown to inhibit the occurrence of AF. OBJECTIVE: The novel objective of this study was to compare the effects of intermittent low- level vagosympathetic nerve stimulation (I-VNS) and continuous low-level vagosympathetic nerve stimulation (C-VNS). METHODS: 19 beagles were randomly divided into 3 groups: Group A, rapid left atrial appendage pacing for 6 hours; Group B, rapid atrial pacing (RAP) for 6 hours and C-VNS (20 Hz, interval 0.1 ms, square wave) with 50% threshold voltage strength; Group C, RAP for 6 hours and I-VNS (continuously recurring cycles of 30-second ON, 30-second OFF). The atrial monophasic action potential (MAP) and the effective refractory periods (ERP) of the atrium and the pulmonary veins were measured at baseline, 1 hour, 3 hours and 6 hours after the experiment began. After the experiment, tyrosine hydroxylase (TH) and choline acetyl transferase (CHAT) expression levels in the anterior right ganglionated plexi (ARGP) from each group were measured. RESULTS: Inter-group comparisons of MAP and ERP demonstrated that Group A was significantly different from Groups B and C (P < 0.05), while the difference between Groups B and C was not significant (P > 0.05). The MAP and ERP in Group A gradually decreased, reaching a minimum at 6 hours, but no significant changes were observed in Groups B and C. When compared to Group A, both Groups B and C had reduced TH and CHAT expression. CONCLUSIONS: During the occurrence and development of AF, I-VNS could protect the cardiovascular system, possibly replacing C-VNS. Additionally, both I-VNS and C-VNS inhibited ganglionated plexus (GP) activity during the AF prevention. PMID- 26131083 TI - Paeoniflorin improves menopause depression in ovariectomized rats under chronic unpredictable mild stress. AB - Paeoniflorin has been shown to effectively relieve neurologic impairments and lessen depression. It remains poorly understood whether it can be used to treat menopause depression; therefore, in the present study, animal model of menopause depression were established by resecting the ovaries in combined with long-term chronic unpredictable stress. Animal model of menopause depression was established by ovariectomy. Sprague-Dawley rats were given 10 mg/kg of paeoniflorin by gastrogavage for 2 weeks. Fluoxetine (2.5 mg/kg) served as a positive control. Sucrose solution consumption test, open-field test, real-time PCR and western blot results demonstrated that paeoniflorin increased sucrose solution consumption, voluntary behaviors and 5-HT1AR mRNA and protein expression. Paeoniflorin decreased the levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol (CORT) and 5-HT2AR mRNA and protein expression in rats with menopause depression. These results indicate that paeoniflorin unregulated 5-HT1AR expression, but downregulated 5-HT2AR expression in brains of rats with menopause depression, and thus exert antidepressant effects. PMID- 26131084 TI - Meta-analysis of acupuncture therapy for the treatment of stable angina pectoris. AB - Angina pectoris is a common symptom imperiling patients' life quality. The aim of this study is to evaluate the efficacy and safety of acupuncture for stable angina pectoris. Clinical randomized-controlled trials (RCTs) comparing the efficacy of acupuncture to conventional drugs in patients with stable angina pectoris were searched using the following database of PubMed, Medline, Wanfang and CNKI. Overall odds ratio (ORs) and weighted mean difference (MD) with their 95% confidence intervals (CI) were calculated by using fixed- or random-effect models depending on the heterogeneity of the included trials. Total 8 RCTs, including 640 angina pectoris cases with 372 patients received acupuncture therapy and 268 patients received conventional drugs, were included. Overall, our result showed that acupuncture significantly increased the clinical curative effects in the relief of angina symptoms (OR=2.89, 95% CI=1.87-4.47, P<0.00001) and improved the electrocardiography (OR=1.83, 95% CI=1.23-2.71, P=0.003), indicating that acupuncture therapy was superior to conventional drugs. Although there was no significant difference in overall effective rate relating reduction of nitroglycerin between two groups (OR=2.13, 95% CI=0.90-5.07, P=0.09), a significant reduction on nitroglycerin consumption in acupuncture group was found (MD=-0.44, 95% CI=-0.64, -0.24, P<0.0001). Furthermore, the time to onset of angina relief was longer for acupuncture therapy than for traditional medicines (MD=2.44, 95% CI=1.64-3.24, P<0.00001, min). No adverse effects associated with acupuncture therapy were found. Acupuncture may be an effective therapy for stable angina pectoris. More clinical trials are needed to systematically assess the role of acupuncture in angina pectoris. PMID- 26131085 TI - ANP/NPRA signaling preferentially mediates Th2 responses in favor of pathological processes during the course of acute allergic asthma. AB - Although atrial natriuretic peptide (ANP) has been well recognized for its role in the regulation of volume-pressure homeostasis in cardiovascular system, its impact on respiratory system, particularly on the pathogenesis of acute allergic asthma, is yet to be elucidated. In the present report, we induced mice with OVA for onset of acute allergic asthma along with the administration of recombinant ANP or A71915 (an antagonist for ANP/natriuretic peptide receptor A, NPRA). It was noted that treatment of mice with ANP significantly promoted inflammatory infiltration in the airway and the production of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) and lung homogenates, and the number of inflammatory cells in the BALF was significantly higher as compared with that of PBS treated asthmatic mice. Moreover, blockade of ANP/NPRA signaling by A71915 almost completely attenuated the effect of ANP administration. Mechanistic studies revealed that ANP repressed the expression of Th1 transcription factor T bet, but enhanced Th2 transcription GATA3 expression. Together, our data provided feasible evidence suggesting that ANP/NPRA signaling predominantly induces a Th2 type response in favor of pathological processes during the course of acute allergic asthma. PMID- 26131086 TI - Effects of Jiangya Xiaoke prescription on TGF-beta1 in diabetic nephropathy rats with hypertension and its mechanisms. AB - OBJECTIVE: To observe the effects of Jiangya Xiaoke prescription on transforming growth factor-beta1 (TGF-beta1) in diabetic nephropathy (DN) with hypertension rats and to investigate its mechanisms. METHODS: DN with hypertension models were made by 4 weeks high-salt diet with high sugar and fat for male Wistar rats, and intraperitoneal injection of streptozotocin (STZ). The model rats were randomly divided into three groups: untreated model group (n = 15); metformin group (n = 15), orally given metformin; Prescription group (n = 15), orally administrated JXR, for 8 weeks respectively. Blood pressure was measured before modeling and after treatment of 2, 4, 8 weeks. Fasting blood glucose (FBG), total triglyceride (TG) and total cholesterol (TC) and urine albumin excretion (UAE) of rats were observed and recorded. Renal histomorphology with PAS staining was observed by the light microscope. TGF-beta1 in kidney was detected by immunohistochemical assay and TGF-beta1 mRNA in renal cortex was detected by RT-PCR. RESULTS: The base blood pressure of rats has no significant difference before modeling (P > 0.05). After 4 weeks of treatment, compared with model group, blood pressure in metformin group decreased (P < 0.01), blood pressure in Jiangya Xiaoke prescription group was slightly lower (P < 0.05). When 8 weeks, the rebound of blood pressure in metformin group is appropriate with the model, the blood pressure of Jiangya Xiaoke prescription reduced significantly (P < 0.01). Compared with model group, FBG, UAE and TG in Jiangya Xiaoke prescription group and metformin group significantly decreased (P < 0.01), TC levels also decreased (P < 0.05). The level of TGF-beta1 in Jiangya Xiaoke prescription group and the metformin group decreased (P < 0.01), and level of TGF-beta1 in Jiangya Xiaoke prescription group was lower significantly than that in metformin group (P < 0.05). The mRNA expression of TGF-beta1 in Jiangya Xiaoke prescription group and the metformin group was significantly lower than model group (P < 0.01). Pathological changes were ameliorated in Jiangya Xiaoke prescription and metformin group compared with model group. CONCLUSION: Jiangya Xiaoke prescription can regulate blood pressure and improve renal functional morphology through down-regulation of TGF-beta1 and its mRNA expression in DN rats with hypertension. We initially proved that the inhibition effect of TGF-beta1 in Jiangya Xiaoke prescription is better than metformin, and Jiangya Xiaoke prescription can lower blood pressure to normal levels with a better step-down smoothly and a long-term efficacy. PMID- 26131087 TI - Endoscopic endonasal transsphenoidal surgery for treating pituitary adenoma via a sub-septum mucosa approach. AB - A novel sub-suptum mucusa approach was used to investigate the surgical method via an endonasal sub-septum-mucosa approach to pituitary adenoma under endoscopy. In this work, we aim to ensure the quality of operation and to reduce the operation trauma and complications. By endoscopy, the nasal mucosa was incised in the nasal septum, and all mucosal flaps were retained, a sub-septum-mucosa surgical corridor was made where the endoscope was used in the mucosa cavity for operation and to remove the pituitary adenoma. 52 patients (28 women, mean age 46.76 years) underwent endoscopic endonasal transsphenoidal sub-septum-mucosa approach for treating pituitary adenoma. 46 patients (88.5%) underwent gross total removal (GTR) for the tumor; 6 patients (11.5%) went through partial tumor removal (PTR). After operation, all nasal mucosa was retained, no complications such as nasal bleeding, loss of sense of smell or cerebrospinal fluid rhinorrhea. Our results showed that treating pituitary adenoma using endonasal transsphenoidal surgeries by keeping nasal mucosa under neuroendoscopy tend to have smaller trauma. This novel method more advanced since it provides a clear operation field, a flexible transformation of operation modes and leads to less postoperative complications. PMID- 26131088 TI - P57 and cyclin G1 express differentially in proliferative phase endometrium and early pregnancy decidua. AB - OBJECTIVE: To compare the expression of P57 and Cyclin G1 in proliferation endometrium and early pregnancy decidua. METHODS: Human endometrial samples were acquired from normal menstrual cycle women undergoing laparoscopy or hysterectomy for fallopian tubes problems. Decidua were acquired from women in early pregnancy who underwent artificial abortion without any endometrial problems. Twelve were in proliferative phase and 13 were deciduas. P57 and Cyclin G1 mRNA and protein were measured by real-time PCR and Western blot. RESULTS: The expression of P57 mRNA and protein were lower in proliferation phase compared with the early pregnancy decidua. Cyclin G1 mRNA and protein expression were slightly higher in decidua than proliferation endometrium but it had no significant difference. CONCLUSION: P57 and Cyclin G1 may play an important role in the endometrial change during the embryo implantation. PMID- 26131089 TI - Improved antifungal activity of amphotericin B-loaded TPGS-b-(PCL-ran-PGA) nanoparticles. AB - To develop amphotericin B-loaded biodegradable TPGS-b-(PCL-ran-PGA) nanoparticles (PLGA-TPGS-AMB NPs) for fungal infection treatment, PLGA-TPGS NPs and PLGA NPs were synthesized by a modified double emulsion method and characterized in terms of size and size distribution, morphology and zeta potential. Drug encapsulation efficiency, in vitro drug release, and in vitro/vivo tests against Candida glabrata were completed. The data showed that both of the two AMB-loaded NPs (PLGA-AMB NPs, PLGA-TPGS-AMB NPs) achieved significantly higher level of antifungal effects than water suspended AMB. In comparison with PLGA-AMB NPs, PLGA-TPGS-AMB NPs had a stronger protective effect against candidiasis and gained an advantage of prolonged antifungal efficacy. In conclusion, PLGA-TPGS-AMB NPs system significantly improves AMB bioavailability by increasing the aqueous dispersibility and improving the antifungal activity. And this would be an excellent choice for the antifungal treatment of the entrapped drug because of its low toxicity and higher effectiveness. PMID- 26131090 TI - Chemokine receptor CXCR4 expression and lung cancer prognosis: a meta-analysis. AB - The chemokine receptor CXCR4 is a G protein-coupled receptor that plays an important role in several biological processes, such as trafficking and homeostasis of immune cells (like T lymphocytes), alteration of cell skeleton rearrangement and cell migration. To investigate whether the CXCR4 protein impacts on lung cancer prognosis, a meta-analysis was performed. Our meta analysis study involved 2,037 lung cancer patients from 24 studies by a comprehensive search from PubMed, Embase and CNKI databases up to September 2014. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate the relationship. We found that the CXCR4 expression was significantly associated with lymph node metastasis (OR = 3.79, 95% CI: 2.15 6.68), distant metastasis (OR = 3.67, 95% CI: 1.84-7.32), tumor stage (OR = 2.78, 95% CI: 1.77-4.39) and overall survival (HR = 1.63, 95% CI: 1.16-2.30). In conclusion, CXCR4 might be a new prognostic biomarker, and it might become a new diagnosis and therapeutic target in lung cancer. PMID- 26131091 TI - Application of technical strategies for surgical management of adult intrinsic pontine gliomas: a retrospective series. AB - OBJECT: The authors retrospectively analyzed the surgical treatment of adult intrinsic pontine gliomas in their department, and to enhance the understanding of technical strategies to treat this disease. METHODS: 7 patients with intrinsic pontine gliomas were recruited for this study, between January 2011 and June 2013. All patients underwent preoperative MRI and Diffusion Tensor Imaging Fiber Tracking (DTI-FT). In addition, multimodal Intraoperative Neuromonitoring (IOM) and Intraoperative Neuronavigation were also applied during microsurgery. RESULTS: 7 patients with intrinsic pontine gliomas were treated at the West China Hospital of Sichuan University. Mean age, mean duration of symptoms prior to diagnosis, and mean duration of follow-up average time were 38.0 years, 2.0 months, and 23.4 months, respectively. The main presentations were progressive cranial nerve deficits and long tract signs. Total resection was achieved in 3 patients, subtotal resection in 2, and partial resection in 2. Postoperative pathological examination revealed: astrocytoma (WHO II) in 4 cases, anaplastic oligoastrocytoma (AO, WHO III) in one case, and anaplastic astrocytoma (AA, WHO III) in two cases. Postoperative radiotherapy were administered to all patients, and 4 patients with astrocytoma (WHO II) rejected chemotherapy. After 11-39 months of follow-up, patient symptoms were resolved or stable without aggravation except one patient died because of rapidly progressive glioma at 11 months after operation. MRI in other patients showed residual tumor size to be unchanged or without obviously recurrence. CONCLUSION: Combining preoperative MRI with preoperative DTI-FT, surgery can be better assessed and the operation for adult intrinsic pontine gliomas can be maximally and safely resected with the aid of Multimodal IOMs and Intraoperative Navigation during microsurgery. PMID- 26131092 TI - Gene expression profiling of extrahepatic ducts in children with biliary atresia. AB - As an inflammatory obliterative cholangiopathy of neonates, biliary atresia (BA) affects both intrahepatic and extrahepatic bile ducts. Its etiology has remained largely unknown. Gene expression profiling was conduced for extrahepatic bile duct tissues (including porta hepatis & common bile duct) to identify novel targets for further studies of BA. Among these tissues, porta hepatis was regarded as fibrosis group while common bile duct as self-control group. The analysis of gene expression profile in these tissues was performed with Affymetrix human microarray. Quantitative RT-PCR (qRT-PCR) was performed to confirm these results. The differential expressions of genes were identified through fold-change filtering. Gene Ontology (GO) and pathway analyses were performed using standard enrichment computation method. It was found that a total of 140 genes were differentially expressed between porta hepatis and common bile duct tissues, 19 genes up-regulated and 121 genes down-regulated. Moreover, GO analysis found that cell adhesion molecules, extracellular matrix formation, protein digestion & absorption functions may be involved in the pathogenesis of porta hepatis fibrosis. Lastly the qRT-PCR data confirmed that IL7 and CLDN2 were significantly up-regulated and both might be involved in the etiology of BA, the expression level of VCAM1 was positively correlated with severity of liver fibrosis in the BA infants. Our results demonstrated that the expressions of these aberrant genes responding to fibrosis in porta hepatis of patients with BA. Further studies of these genes may provide useful insights into the pathological mechanisms of BA. PMID- 26131093 TI - Hypersplenism: an independent risk factor for myocardial remodeling in chronic heart failure patients. AB - BACKGROUND: During the progression of chronic heart failure (CHF), decreased cardiac functioning is often associated with congestion in the inferior vena vein, which in turn induces splenomegaly and subsequent hypersplenism. Hypersplenism has been shown to exacerbate endothelial dysfunction and adverse cardiac remodeling in HF mice. However, it is unknown whether this effect also occurs in CHF patients with hypersplenism. Here, we compared different patterns of myocardial remodeling between patients with and without hypersplenism. METHODS: 33 CHF patients with hypersplenism were selected and carefully examined. Clinical data and baseline hemogram measurements were included in the evaluation. Another 35 CHF patients were randomly chosen as controls. All patients received formal HF treatment to ameliorate their symptoms and to preserve heart structure and functioning. Peripheral blood-derived endothelial progenitor cells (EPCs) were cultured, and the experimenters were blinded to the patients' clinical characteristics. The biological properties of the cells were then compared. The groups were also compared in terms of the free plasma hemoglobin and heme levels, endothelial adhesion molecule expression, left ventricular ejection fraction (LvEF) and cardiovascular events (re-PCI, re-myocardial infarction, stent thrombosis, stroke and death due to cardiovascular or vascular causes). RESULTS: The free plasma hemoglobin and heme levels were significantly higher in the CHF patients with hypersplenism compared with the controls (P<0.001). Additionally, the CHF patients with hypersplenism had increased levels of VCAM-1, ICAM-1, P selectin and E-selectin (P<0.001). Echocardiography revealed a significant reduction in the LVEF in these patients compared with the controls at the 24(th) month (P=0.013). During a mean follow-up period of 24+/-1 months, cardiovascular events were observed in 16 patients in the CHF with hypersplenism group and 9 patients in the control group. Univariate Kaplan-Meier analysis further revealed a significant difference between the groups (P=0.021). The mRNA levels of endothelial NO synthase enzyme (eNOS) in EPCs from the CHF patients with hypersplenism were significantly lower than those in the control subjects (P<0.001). We also observed decreased proliferation potential of EPCs from the CHF patients with hypersplenism (P<0.001). Further, a significant increase in TUNEL(+) EPCs was observed in the CHF patients with hypersplenism after 6 h of stimulated ischemia compared with the control subjects (P<0.001). CONCLUSIONS: CHF patients with hypersplenism are susceptible to myocardial remodeling. Increased oxidative stress and endothelial dysfunction caused by excess free plasma hemoglobin and heme may partially explain this causality. PMID- 26131094 TI - Comparison of core decompression and conservative treatment for avascular necrosis of femoral head at early stage: a meta-analysis. AB - The purpose of the current meta-analysis was to compare the efficacy of core decompression (CD) and conservative treatment (CT) for saving femoral heads in patients with avascular necrosis of femoral head (ANFH). Four RCTs and two CCTs involving 323 hips with 24- to 48-months follow-up were included in this review. Our results suggested CD had a trend of favorable results in contrast to other CT (OR 3.28; 95% CI 0.77-14.02; P = 0.11) but saved much less hips compared to biophysical treatments [odds ratio (OR) 0.37; 95% CI 0.18-0.74; P = 0.005]. In the stratified survival rate analysis by ANFH stage, interestingly, CD group got a significantly higher successful rate of hip joint conservation than other CT group in both stage I and stage II-III (stage I: OR 4.43; 95% CI 1.34-14.65; P = 0.01; stage II-III: OR 6.75; 95% CI 2.18-20.90; P = 0.0009). In the biophysical stimulation subgroup, however, an even higher frequency of survived hips were observed compared to CD group at stage II-III (CD vs. biophysical stimulation: OR 0.34; 95% CI 0.17-0.67; P = 0.002). In conclusion, performing CD for ANFH is effective for preventing femoral collapse within a short-term follow-up, but an even higher successful rate were expected by biophysical stimulations. Nevertheless, the short-term follow-up, the small sample size of the current meta analysis only provide limited quality of evidence, which required confirmation from further large-scale, well-designed RCT with longer follow-up. PMID- 26131095 TI - Anatomy and CT reconstruction of the anterior area of sphenoid sinus. AB - BACKGROUND: The anatomical structures of anterior area of sphenoid sinus are observed by CT reconstruction of radiographic images in some studies. However, the detailed anatomic information of the extended transsphenoidal approach is still incomplete. METHOD: Fifteen cases (30 sides) of adult cadaveric skulls and 20 cases (40 sides) of bleached adult dry skulls were observed and measured under microscope. CT imaging data were obtained from 12 patients. RESULTS: Anatomy of anterior area of sphenoid sinus and sphenopalatine artery observed from CT three dimensional reconstructed images was consistent with that observed from adult cadaveric skulls and bleached adult dry skulls. The anterior sphenoid sinus wall resembled a bird head, with midline protrude prismatically. The sphenoid ostia on both sides were in shape of bird-eyes, and the sphenoidal rostrum below was like the beak. The "shallowest point" was firstly reported in this study and was defined as the nearest point from the nostril to the anterior sphenoid sinus wall. It was located about 5.5 mm from sphenoid sinus ostium, and 5 mm from the upper edge of the posterior choanae. It was an important anatomical reference mark in locating the sphenoid sinus ostium in the anterior sinus wall. CONCLUSION: The three-dimensional images reconstructed by CT scan can visually display the bone structure of anterior area of sphenoid sinus, sphenopalatine artery and its main branches. Virtual endoscopy reconstruction can confirm the structural details of CT reconstruction and simulate transsphenoidal surgery. PMID- 26131096 TI - Budesonide mitigates pathological changes in animal model Of COPD through reducing neutrophil elastase expression. AB - OBJECTIVES: This study was conducted to investigate a molecular mechanism by which budesonide inhalation may mitigate pathological responses of cigarette smoke-induced COPD. METHODS: Rats were exposed to air (control) and cigarette smoke (smoking) in the presence and absence of budesonide. Cell count in bronchoalveolar lavage fluid (BALF), lung function test, mean liner intercept in lung tissue, mean alveolar number, right ventricular hypertrophy index (RVHI) and morphological changes in lungs were assessed, respectively. Alpha-1 antitrypsin (A1AT) and neutrophil elastase (NE) mRNA expression in lung tissues and their protein productions in BALF were examined as well. RESULTS: Smoking rats showed significant changes in the above assessments as compared to those of the control rats (all P < 0.01 or 0.05). Budesonide applied for the smoking rat significantly decreased differential cell counts in BALF and ameliorated lung function and RVHI (P < 0.01 or 0.05) with mitigated peribronchiolar inflammation and pulmonary bullae formation in the smoke-exposed lungs. Treatment with budesonide resulted in obvious decreases in NE mRNA and protein expression levels (both P < 0.05). CONCLUSION: Budesonide inhalation serves to improve lung function and right ventricular dysfunction through attenuating pulmonary inflammatory response and NE expression level in the diseased lungs. PMID- 26131098 TI - Surgical management of giant neurofibroma in soft tissue: a single-center retrospective analysis. AB - Neurofibroma, a common benign tumor in soft tissue, continues to grow, and often appears to be giant. In this study, we retrospectively analyzed the surgical treatment of 26 patients with giant neurofibromas in our clinic in the past 10 years from Jan. 2004 to Dec. 2013. The tumors were located in the head (n = 10), trunk (n = 9), limbs (n = 5), and multi-sites (n = 2). According to the location and extent of the lesion, as well as the adjacent anatomy, surgical management was performed to partially (n = 15) or almost completely (n = 11) resect the tumor. The wounds were repaired by skin flap or skin graft. Among them, one child with a giant tumor in the scalp underwent three times of skin expander treatment, and acquired complete removal of the tumor finally without baldness. Eleven cases underwent the interventional embolization of tumor's nutrient arteries, which successfully reduced the bleeding in operation. Most of the skin flap and skin graft survived well. After operation, the appearance of the patients and the function of the limbs were improved largely. In conclusion, for the giant neurofibroma, surgical treatment effectively reduces the tumor burden, rehabilitates the appearance and function, and so improves the quality of life. Skin expandor and interventional embolization of nutrient artery can be used when appropriate. PMID- 26131097 TI - Expression of phosphorylated Akt/mTOR and clinical significance in human ameloblastoma. AB - This study aimed to evaluate the expression of AKT and phosphorylated AKT (p-Akt) in human ameloblastoma (AB). Immunohistochemistry showed human AB was positive for Akt and Akt expression was mainly found in the cytoplasm of epithelial cells. The Akt expression in AB was significantly higher than that in normal oral mucosa (NOM), but still lower than that in oral squamous cell carcinoma (OSCC). NOM was negative for p-Akt, but AB was positive for p-Akt. In some AB tissues, p-Akt expression was found in both cytoplasm and nucleus. Akt expression in AB was significantly different from that in NOM and OSCC. The p-Akt in AB was markedly higher than that in NOM, but lower than that in OSCC. mTOR expressed in cytoplasm in AB, but not in NOM. P-mTOR expressed on cell membrane in NOM, while in cytoplasm and nucleus in Ab. Results of western blot assay showed that Akt expression was found in all the AB tissues, and increased in tissues with malignant transformation. In addition, the p-Akt expression also markedly increased in AB, but was still lower than that in OSCC tissues. Compared to NOM, mTOR and p-mTOR expression significantly increased in AB. BandScan 5.0 software was used to detect the optical density of protein bands. Results showed p-Akt, mTOR and p-mTOR expression in AB was markedly different from that in control group. PMID- 26131099 TI - Immune tolerance of mice allogenic tooth transplantation induced by immature dendritic cells. AB - As a common procedure in dentistry for replacing a missing tooth, allogenic tooth transplantation has encountered many difficulties in the clinical application because of immunological rejection. It is hypothesized that immature dendritic cell injection might be a potential alternative method to avoid or alleviate immunological rejection in allogenic tooth transplantation. To test this hypothesis, a mouse model of allogenic and autogeneic tooth transplantation was to established test the immunosuppressive effect of immature dendritic cells (imDCs) derived from donor bone marrows on transplant rejection in allogenic tooth transplantation. 2 * 10(6) imDCs generated with 50 U/ml GM-CSF were injected to each recipient mouse by two ways: tail vein injection 7 days before transplantation or regional dermal injection at day 0 and day 3 after transplantation. Groups of autogeneic tooth transplantation and allogenic tooth transplantation without any treatment were set as control groups. The effects were evaluated with histopathology and immunohistochemistry. We found there was no obvious rejection in autogeneic tooth transplantation group; tail intravenous injection group showed obviously alleviated rejection while local injection group and none-treatment allogenic tooth transplantation group both showed severe rejection. Our results suggested that the rejection of allogenic tooth transplantation could be alleviated by tail vein injection of donor bone marrow derived imDCs though it could not be completely eliminated. The clinical application of imDCs in allogenic tooth transplantation still needs further deep research. PMID- 26131100 TI - SIRT3 inhibits cell proliferation in human gastric cancer through down-regulation of Notch-1. AB - SIRT3 is a member of the NAD+-dependent class III deacetylase sirtuin family and plays pivotal roles in regulating cellular functions. Accumulating evidence has recently demonstrated that SIRT3 may function as either oncogene or tumor suppressor in a panel of cancers. However, the biological function of SIRT3 in gastric cancer has been poorly characterized. The present study revealed that the mRNA and protein levels of SIRT3 were significantly reduced in human gastric cancer tissues and cell lines. In addition, overexpression of SIRT3 dramatically suppressed the proliferation ability and colony formation number of gastric cancer cells. By contrast, SIRT3 knockdown using small interfering RNA enhanced tumor cell growth and colony formation. On the molecular level, we found that SIRT3 inhibited the expression of Notch-1 both at the mRNA and protein levels in gastric cancer cells. Furthermore, Notch-1 overexpression diminished the inhibitory effects of SIRT3 on tumor cells proliferation. Taken together, these results demonstrated that SIRT3 suppressed the proliferation gastric cancer cells via down-regulation of Notch-1, which might provide novel therapeutic targets in the gastric cancer therapy. PMID- 26131101 TI - Investigation of RNA interference suppression of matrix metalloproteinase-9 in mouse model of atherosclerosis. AB - OBJECTIVE: To investigate the effect of RNA interference of matrix metalloproteinase (MMP)-9 on atherosclerosis on atherosclerosis in apolipoprotein E (ApoE)-/- mouse. METHODS: ApoE-/- mouse strain and three cell lines (293T, NIH3T3 and Raw264.7) were used in the present study to investigate the effect of MMP-9 silencing by RNA interference. Thirty 10-week-old ApoE-/- mice were randomly assigned to a control group, lentiviruses with naked vector group and Lentiviruses-MMP-9 intervention group (n = 10). Aortic atherosclerotic plaques of the mice were stained with immunohistochemical techniques, the MMP-9 and high sensitivity C-reactive protein levels of three groups were detected simultaneously. Expression of MMP-9 was significantly down-regulated in interference group. MMP-9 and high-sensitivity C-reactive protein levels in MMP-9 interference group were significantly lower than that of the control group. CONCLUSION: The expression of MMP-9 is closely related to vulnerability of atherosclerotic plaques. Silencing of MMP-9 expression acts as a positive role in maintenance of atherosclerotic plaque stability. The present study provides novel experimental insight for the treatment of vulnerable plaques in atherosclerosis. PMID- 26131102 TI - The effects of sodium tanshinone IIa sulfonate pretreatment on high glucose induced expression of fractalkine and apoptosis in human umbilical vein endothelial cells. AB - The development of diabetes mellitus (DM) and its complications is a chronic inflammatory response process, chemokines and their receptors play an important role in this course of events. The aim of this study is to observe the effects of sodium tanshinone IIa sulfonate (STS) on high glucose-induced fractalkine (FKN) level, and investigate possible mechanisms of STS works. HUVECs cells were employed to explore the effects of STS on FKN protein. TUNEL assay was used to detect the apoptosis rate of HUVECs. Immunohistochemistry was utilized to detect the beta-actin and P-GSK-3beta (Ser9) protein expression. Immunofluorescence was employed to detect FKN protein expression. Real-time RT-PCR was used to examine beta-actin, GSK3beta and FKN mRNA expression. The results indicated that the STS treatment could significantly decrease the apoptosis rate caused by high-glucose (P < 0.05). STS improves beta-catenin and p-GSK-3beta (Ser9) expression, and inhibits FKN levels induced by high glucose. STS inhibited GSK-3beta and FKN mRNA induced by high glucose. In conclusion, STS may play the role of anti- inflammatory by regulate canonical Wnt pathway to inhibit the expression of FKN induced by high glucose. PMID- 26131103 TI - Alkannin inhibits growth and invasion of glioma cells C6 through IQGAP/mTOR signal pathway. AB - OBJECTIVE: This study aims to explore the effect of alkannin on the growth and invasion of glioma cells and its mechanism. METHODS: The effects of alkannin on the growth and invasion of glioma cells were detected with MTT assay, clone forming test and transwell assay. The effects of alkannin on the cell cycle were detected with flow cytometry assay. The changes of cyclin, MMPs and IQGAP/mTOR signal pathway related proteins were detected with western blotting methods. RESULTS: Alkannin (1 MUM, 3 MUM and 10 MUM) can significantly inhibit the growth, proliferation, migration and invasion of glioma cells C6 with dose dependent. Alkannin can block cell cycle in G1 phase with the increased concentration, which was related with the down-regulation of cyclinA1, cyclinA2 and cyclinD1 expression. Alkannin can also down-regulate the expression of MMP 2, MMP 9 and IQGAP. Alkannin has no effect on mTOR but can inhibit the phosphorylation of mTOR. CONCLUSIONS: Alkannin can inhibit the growth and invasion of glioma cells C6 through IQGAP/mTOR signal pathway. PMID- 26131104 TI - Hydroxysafflor yellow A inhibits lipopolysaccharide-induced proliferation and migration of vascular smooth muscle cells via Toll-like receptor-4 pathway. AB - Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is closely associated with early vascular hyperplasic lesions. Toll-like receptor (TLR)-4 is a pathogen pattern recognition receptor expressed on VSMCs, and can be activated by lipopolysaccharide. Activated TLR-4 plays a promoting role in VSMCs proliferation and migration through the downstream signaling pathways including Rac1/Akt. Hydroxysafflor yellow A (HSYA) is the main component of the safflower yellow pigments, which has long been used for the treatment of cardiovascular diseases in traditional Chinese medicine. However, the effect of HSYA on VSMC proliferation and migration remains unknown. In the present study, we showed that HYSA could inhibit LPS-induced VSMCs proliferation and migration, accompanied by the downregulated levels of several key pro-inflammatory cytokines, including TNF alpha, IL-6, and IL-8. We further showed that HYSA inhibited LPS-induced upregulation of TLR-4 expression as well as the activation of Rac1/Akt pathway, suggesting that HSYA inhibits LPS-induced VSMCs proliferation and migration, partly at least, via inhibition of TLR-4/Rac1/Akt pathway. Accordingly, HSYA may be used as a promising agent for prevention and treatment of vascular hyperplasic disorders. PMID- 26131105 TI - Perforator pedicled sural neurocutaneous vascular flap: a modeling study in the rabbit. AB - BACKGROUND: An animal model of a distal pedicled sural neurocutaneous flap for experimental research has not previously been established. The purpose of this study was to construct a sural neurocutaneous vascular flap model in the rabbit. MATERIALS AND METHODS: Thirty-five New England rabbits were divided into four groups. Five rabbits in Group A were used for an anatomical study. Red latex and gelatin-lead oxide were injected into posterior tibial arteries of five rabbits in Groups B and C, respectively. In Group D, 40 neurocutaneous flaps with a single perforator pedicle were raised bilaterally in twenty rabbits. In the right legs, 20 flaps were raised by the normal procedure. In the left legs, the perforator pedicles of 20 flaps were ligated as controls. RESULTS: The sural nerve originated from the posterior tibial nerve. Its accompanying artery originated from the deep femoral artery and ran to the lateral malleolus following the sural nerve. A perforator of the posterior tibial artery at the superior calcaneus originated from the midpoint of the connecting line between the medial malleolus and calcaneus, and was 0.46 +/- 0.03 mm in diameter at its origin. The survival rate of the flaps in the right leg 10 days after operation was 64.7 +/- 8.7%. Flaps on the left side underwent total necrosis. CONCLUSION: The distal single perforator-based sural neurocutaneous vascular flap in the rabbit presents with anatomical stability, is easy to harvest, and has a reliable arterial supply. The developed method represents a useful animal model for the study of single perforator-based neurocutaneous vascular flaps. PMID- 26131106 TI - Distribution and gene mutation of enteric flora carrying beta-glucuronidase among patients with colorectal cancer. AB - OBJECTIVE: To explore the difference of distribution in intestinal flora among colorectal cancer patients and healthy controls and investigate characteristics and changes of sequences in beta-glucuronidase (beta-glucuronidase, beta-G). METHODS: Bacterial genomic DNA and E. coli DNA in feces were extracted from colorectal cancer patients and healthy controls respectively. Specific primers for beta-G gene were designed and amplified by PCR as templates of fecal bacteria genomic DNA and E. coli DNA respectively. RESULTS: Compared with normal control, the amount of E. coli in cancer group increased significantly, Lactobacillus and Bifidobacterium probiotics reduced significantly, and proportional quantity of anaerobic bacteria and aerobic bacteria reversed. The intestinal flora carry beta G in both groups, and homologies with uidA gene sequences encoding the beta-G were 99% and 98% respectively. In colorectal cancer group the 1141th and 1148th A base were deleted. The 1149th A base mutated into T base, and the 1158th bit A base mutated into G base; however, in healthy control group the 1141th and 1148th position A base was deleted, and the 1149th A base mutated into T base. CONCLUSION: There are differences of intestinal flora distribution between cancer group and healthy control group. The gene mutation and deletion of intestinal flora of beta-G gene appear at the same time at 1141th, 1148th and 1149th in both cancer group and healthy control group, and 1158th genetic mutation appears only in colon cancer group. PMID- 26131107 TI - Association of interleukin-12 gene polymorphisms with cancer susceptibility: a meta-analysis. AB - OBJECTIVE: To evaluate the association between interleukin-12 (IL-12) gene polymorphism and cervical cancer susceptibility. METHODS: We comprehensively retrieved the relevant English and Chinese database to collect case-control studies on the association between the IL-12 gene polymorphism and cervical cancer susceptibility. Data were extracted independently by two researchers respectively, the summary data were analyzed using Revman 5.2 software, the association was described using odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: According to inclusion and exclusion criteria, 5 case-control studies involving 2552 cervical cancer patients and 2232 healthy controls were included. The meta-analysis results showed that 3'UTR+1188 (rs3212227) polymorphism in IL-12 gene was not associated with cervical cancer risk (C vs. A: OR=1.09, 95% CI: 0.88~1.35, P=0.45; AA+AC vs. CC: OR=0.88, 95% CI: 0.67~1.15, P=0.34; AA vs. AC+CC: OR=0.89. 95% CI: 0.56-1.42, P=0.62; CC vs. AA: OR=1.30. 95% CI: 0.79-2.12, P=0.30). CONCLUSION: The available evidence suggested that rs3212227 polymorphism in IL-12 gene may not be the risk factor to cervical cancer. PMID- 26131108 TI - Coblation assisted transnasal endoscopic resection of nasopharyngeal cyst: 10 years experience and outcomes. AB - OBJECTIVES: To determine the outcomes of coblation assisted transnasal endoscopic resection of nasopharyngeal cyst. METHOD: Retrospective chart review outcomes in 12 patients who underwent endoscopic resect cysts of the nasopharynx at our department between 2001 and 2010. Twelve patient, aged 28 to 71 years, with cysts of the nasopharynx. The outcome variables of complications and the rate of recurrence were analyzed, respectively. RESULTS: In 12 cases, retention cysts in 2 cases, branchial cyst in 1 case, adenoid middle fossa cyst infection in 6 cases, Tornwaldt's cyst in 3 cases. The use of the coblation device was associated with a significant decrease in blood loss. There were no postoperative complications, and the overall follow-up period was 2-7 years and shows no signs of recurrence. CONCLUSIONS: We describe transnasal endoscopic procedures to resect cysts of the nasopharynx. We found that radiofrequency coblation is a useful and safe tool associated with minimal blood loss in the resection of these cysts. In our experience, it has been a highly successful, safe, and effective procedure. PMID- 26131109 TI - MiR-29a suppresses prostate cell proliferation and induces apoptosis via KDM5B protein regulation. AB - Small regulatory RNAs, known as microRNAs, regulate gene expression at the post transcriptional level; such as protein translation inhibition or mRNA degradation. Altered miRNA expressions have been implicated in various cancers. In present studies, it was demonstrated that microRNA-29a (miR-29a) expressions were significantly lower in prostate cancer (PCa) patient samples, but the role of microRNA-29s in PCa remains unclear. KDM5B was highly expressed in PCa cancer cells. Bioinformatics analysis revealed a conserved target site for miR-29a in the 3-untranslated region (UTR) of KDM5B. Gain-of-function studies using mature miR-29a were performed to investigate cell proliferation and apoptosis in two PCa cell lines (LNCaP and PC-3). We utilized gene expression analysis and in silico database analysis to identify miR-29a-mediated molecular pathways and targets. We showed that miR-29a significantly suppressed the activity of a lucifarice reporter containing KDM5B-3'UTR, which was not observed in cells transfected with mutated KDM5B-3'UTR. Gene expression data demonstrated that KDM5B expression was lower in noncancerous prostatic cell WPMY-1 than in the four PCa cell lines (LNCaP, 22RV1, PC-3 and DU145). Moreover, the enforced expression of miR-29a in PC-3 and LNCaP cells inhibited proliferation, and induced apoptosis by repressing the expression of KDM5B. This study revealed that the aberrant expression of miR 29a in PCa cells regulated KDM5B expression levels associated with tumor dissemination. These findings may be utilized in developing novel therapeutic tools for PCa. PMID- 26131110 TI - Amyloid-beta immunization enhances neurogenesis and cognitive ability in neonatal mice. AB - Whether Abeta actually has a physiological as well as a pathological role is not known. In order to investigate the effect of endogenous Abeta, wild type C57BL/6 mice were immunized with human or mouse derived Abeta1-42. The anti-Abeta antibody concentrations were increased in both treated groups. Compared to the human Abeta1-42 treated group, level of serum Abeta significantly decreased in mouse Abeta1-42 treated group. Western blot results revealed that these two derived Abeta1-42 had no cross-reaction. The new dentate granule survival cells increased in Abeta1-42 immunization groups, indicated by more BrdU+/NeuN+ and BrdU+/DCX+ cells as compared to PBS-treated group, accompanied by behavioral performance improving in a hippocampus-dependent learning task. Immunohistochemical analysis showed that BrdU+/Iba1+ cells also increased, however new born astrocytes (BrdU+/GFAP+) were unaffected in all treated mice. Interestingly, according the results of ELISA analysis both vaccines up-regulated IL-4 and IFN-gamma levels in the brains and sera, but the TNF-alpha level did not changed. Of note, human Abeta1-42 immunization in neonatal mice enhanced neurogenesis and cognitive ability, might via Abeta immune response rather than cleaning endogenous Abeta. PMID- 26131111 TI - Neuroglobin protects cardiomyocytes against apoptosis and cardiac hypertrophy induced by isoproterenol in rats. AB - Neuroglobin (Ngb) is well known as a physiological role in oxygen homeostasis of neurons and perhaps a protective role against hypoxia and oxidative stress. In this study, we found that Ngb is expressed in rat heart tissues and it is related to isoproterenol induced cardiac hypertrophy. Moreover, overexpression or knock down of Ngb influences the expression of hypertrophic markers ANP and BNP and the ratio of hypertrophic cells in rat H9c2 myoblasts when isoproterenol treatment. The Annexin V-FITC/PI Staining, Western blot and qPCR analysis showed that the involvement in p53-mediated apoptosis of cardiomyocytes of Ngb is might be the mechanism. This protein could prevent the cells against ROS and POS-induced apoptosis not only in nervous systems but also in cardiomyocytes. From the results, it is concluded that Ngb is a promising protectant in the cardiac hypertrophy, it may be a candidate target to cardiac hypertrophy for clinic treatment. PMID- 26131112 TI - The downregulation of OPN inhibits proliferation and migration and regulate activation of Erk1/2 in ECA-109 cells. AB - Osteopontin (OPN) involves in tumor formation, and strongly correlated with the tumor progression. It was overexpressed in human esophageal squamous cell carcinoma (ESCC). To study the molecular mechanisms of OPN in ESCC, we examined its roles in inhibiting proliferation and invasion of ECA-109 (esophageal squamous cell carcinoma) cells. The expression of OPN gene was knockdown by RNA interference (RNAi) in the Eca-109 cell. The transcription level of OPN was to detect by reverse transcription-quantitative PCR (RT-qPCR). Western blot assay was performed to detect the expression of OPN, Caspase-3,Caspase-8, Caspase-9, ERK1/2, phospho-ERK1/2 and MMP2 after RNAi. The cell proliferation and apoptosis were detected by MTT and Hoechst33342 assay. Transwell inserts was used for detecting ECA-109 cell's migration ability. The results shown that the level of OPN mRNA and protein was significantly reduced after RNAi. Proliferation and migration of cell line (ECA-109) was significantly inhibited in vitro. The protein phosphorylation and activation of ERK1/2 in the OPN RNAi group reduced significantly than the negative control groups. In Conclusion, the proliferation and migration of human ESCC can be inhibited by RNAi-targeting OPN. OPN can promote the expression of MMP2 through the ERK signaling pathways. OPN could serve as a potential therapeutic target for human ESCC. PMID- 26131113 TI - Guidance value of MRI for transsphenoidal surgery of pituitary adenomas with cystic degeneration. AB - OBJECTIVE: This study is to evaluate the surgical outcomes of transsphenoidal surgery in pituitary adenoma (PA) patients with cystic degeneration by using MRI. METHODS: Eighty-three patients with surgically and pathologically confirmed PA were enrolled. They were divided into three groups according to preoperative MR images: substantive adenoma group (n = 40), cystic degeneration without fluid fluid level group (n = 19), cystic degeneration with fluid-fluid level group (n = 24). The PA was removed by transsphenoidal surgery and the surgical outcomes were retrospectively compared. RESULTS: The number of cases with abundant blood supply was 17 cases (42.5%) in substantive adenoma group, 13 cases (68.4%) in cystic degeneration without fluid-fluid level group and 16 cases (66.7%) in cystic degeneration with fluid-fluid level group. Blood supply in cystic degeneration with fluid-fluid level group was significantly richer than that in substantive adenoma group (P < 0.05). Peritumoral adhesion was significantly greater in cystic degeneration with fluid-fluid level group than in substantive adenoma group. And, PA with fluid-fluid level has significantly lower tumor total resection rate and MVD as well as higher recurrence rate (P < 0.05). Differences in cerebrospinal fluid leakage and postoperative diabetes insipidus were both not significant among the three groups (P > 0.05). CONCLUSIONS: Compared with other types of PA, cystic degeneration with fluid-fluid level were often richer in blood supply, greater in adhesion with peritumoral structures and easier to be found with tumor residual. Thus, more patience should be needed during the surgeries and more dynamic reviews are required postoperatively. PMID- 26131114 TI - Prognostic role of elevated platelet count in patients with lung cancer: a systematic review and meta-analysis. AB - Recently, more and more studies have shown that platelet count (PLT) may be associated with the prognosis of lung cancer (LC). However, the prognostic role of PLT in lung cancer is still controversial. In the present study, we conducted a meta-analysis of all available English studies to evaluate the prognostic value of PLT in lung cancer. In order to investigate the association between PLT and overall survival (OS), the hazard ratio (HR) and its 95% confidence interval (CI) was evaluated. The odds ratio (OR) with its 95% confidence interval (CI) was used to assess the relationship between PLT and clinicopathological parameters. There were 12 studies (n = 5,884) were involved in this meta-analysis. The pooled results showed that elevated PLT was a negative predictor for OS and the pooled HRs was significant at 1.74 (95% confidence interval, 1.39-2.19). Elevated PLT was also significantly associated with advanced TNM stage (OR: 2.65, 95% CI: 1.77 3.97) and smoking history (OR: 2.70, 95% CI: 1.79-4.08). In addition, there was no significant correlation between elevated PLT and squamous cell carcinoma (OR: 1.54, 95% CI: 0.77-3.07). Our results demonstrated that elevated PLT denotes a poor prognosis in patients with LC. PMID- 26131115 TI - Association between CCR6 and rheumatoid arthritis: a meta-analysis. AB - OBJECTIVE: Chemokine (C-C motif) receptor 6 gene (CCR6) polymorphism has been reported to be associated with rheumatoid arthritis (RA) in different ethnic populations. Moreover, its inhibition by monoclonal antibody in mouse model has suppressed arthritis. However, few replication studies have reported conflicting results about this association. Therefore, to establish that CCR6 indeed is a risk factor associated with RA among different ethnic populations, a comprehensive meta-analysis study was conducted. METHODS: PubMed and MEDLINE databases were searched using the term 'CCR6' for all articles published before May 2014. All the replication studies examining the association between CCR6 and RA were reviewed for meta-analysis. Data were summarized using random-effects meta-analysis. The heterogeneity and publication bias among studies were examined by chi(2) -based Q statistic test and Egger's test, respectively. RESULTS: A total of 24955 RA patients and 56129 controls from seven articles were included in the meta-analysis. While CCR6 was a risk factor in Asian (OR = 1.19, 95% CI: 1.14-1.24) and European (OR = 1.14, 95% CI: 1.08-1.21) populations, it was indicated as a protective factor in African Americans (OR = 0.79, 95% CI: 0.62 0.96). CONCLUSIONS: Our meta-analysis study concludes that there is a significant association between CCR6 and RA in all racial groups except African-American subgroup, which require a large sample size for concrete prediction. PMID- 26131116 TI - Mutation of the epidermal growth factor receptor gene and its impact on the efficacy of gefitinib in advanced non-small cell lung cance. AB - Mutations in the epidermal growth factor receptor (EGFR) gene are associated with subsets of non-small cell lung cancer (NSCLC). Some patients with EGFR mutations are responsive to targeted therapy with the EGFR tyrosine kinase inhibitor gefitinib. Here, the mutation status of EGFR was assessed in advanced-stage NSCLC patients to determine how mutation status influences the clinical efficacy of gefitinib. The study included 106 patients with advanced NSCLC who were treated with gefitinib. Exons 19 and 21 of EGFR were sequenced from tumor tissues samples by PCR, and patient clinical characteristics, short-term outcomes (partial response, stable disease, progressive disease), and survival [overall survival (OS) and progression-free survival (PFS)] were compared. EGFR mutations in either exon 19 or exon 21 were detected in 54.7% of cases. The EGFR gene mutation rate was significantly different in patients with different pathological types (chi(2)=6.612, P<0.05). The distribution of short-term outcomes differed significantly by EGFR gene mutation status, history of smoking, and bone metastasis (chi(2)=6.481~35.938, P<0.05). Further, OS and PFS was significantly higher following gefitinib in patients with EGFR mutations than those without EGFR mutation (chi(2)=19.135, 6.953, P<0.05). OS was also significantly higher in patients with an exon 19 deletion mutation than in those with the exon 21 point mutation (chi(2)=8.575, P<0.05). Cox multivariate regression analysis indicated that OS was correlated with the pathological type of the tumor (HR=4.877), US Eastern Cooperative Oncology Group Physical Status (ECOG PS) score (HR=3.087), and EGFR mutation status (HR=1.876) (all P<0.05), while PFS was correlated with ECOG PS score (HR=2.218), cycles of chemotherapy (HR=1.829), and EGFR mutation status (HR=1.840) (all P<0.05). Only mild adverse events were reported during gefitinib treatment. The findings indicate that gefitinib treatment can improve the clinical outcomes of NSCLC patients with EGFR mutation, prolonging their survival time with only mild adverse events. PMID- 26131117 TI - Butyrate protects rats from hepatic ischemia/reperfusion injury. AB - BACKGROUND: Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock and trauma. The use of butyrate, which acts as a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, provides anti-oxidant and anti-apoptotic effects. METHODS: Male Sprague-Dawley (SD) rats model of HI/R were subjected to a partial (70%) hepatic ischemia for 45 minutes (min) after pretreatment with either saline or butyrate, followed reperfusion. 30 rats were randomly allocated to three main experimental groups (n = 10 each): (1) The sham-operated group underwent laparotomy without hepatic ischemia. (2) Butyrate was injected into the tail vein in the butyrate group 30 min before HI/R. (3) The control group underwent the same procedure as the butyrate group but with administration of physiological saline. Rats from each group were randomly euthanized to collect blood and liver samples. RESULTS: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. SD rats that received butyrate displayed reduced HI/R injury compared with controls. Use of butyrate reduced the histologic injury and significantly decreased serum Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. In addition, butyrate decreased myeloperoxidase (MPO) activity and malondialdehyde (MDA) tissue contents. Apoptotic cells in I/R rats were also significantly reduced after butyrate treatment. Furthermore, butyrate also decreased the mean number of apoptotic cells (positively stained for TUNEL) and increased the mean number of proliferating cells (positively stained for Ki-67). The expression levels of TNF-alpha and IL-6 were attenuated after butyrate treatment. CONCLUSIONS: Our results suggest that butyrate attenuated I/R-induced liver injury through upregulation of intracellular anti oxidant stress and anti-apoptotic signaling pathways. PMID- 26131118 TI - Increased ADRP expression in human atherosclerotic lesions correlates with plaque instability. AB - Adipose differentiation-related protein (ADRP) is intrinsically associated with the surface of lipid droplets implicated in the development of atherosclerosis. We analyzed expression of ADRP in human popliteal artery plaques. Atherosclerotic plaque tissue from the popliteal artery was obtained from 18 patients undergoing lower extremity amputation for arteriosclerosis obliterans, and with either stable (n = 6) or unstable (n = 12) atherosclerotic plaques. Plaques were histologically classified as either unstable (>= 40% lipid core plaque area) or stable (< 40% lipid core plaque area). Control tissues consisted of sections of mesenteric arteries obtained from 10 patients without a history of atherosclerosis, but undergoing a subtotal gastrectomy. Plaque tissues were analyzed for expression of ADRP and protein kinase C (PKC) protein by immunohistochemical methods, and ADRP mRNA expression was measured using the reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical analyses showed that ADRP expression was higher in samples of unstable plaque when compared with expression in stable plaque (gray intensities 103.56 +/- 1.187 vs 106.95 +/- 1.389, respectively, P < 0.05) and that ADRP expression was associated with increased PKC expression (gray intensities 102.32 +/- 1.730 vs 104.70 +/- 0.959, respectively, P < 0.01). Consistent with ADRP protein expression, expression of ADRP mRNA was also higher in unstable plaque compared to expression in stable plaque (relative expression 1.17 +/- 0.15 vs 0.81 +/- 0.03, respectively, P < 0.05). IN CONCLUSION: this study demonstrated that increased expression of ADRP in human atherosclerosis was associated with plaque instability. PMID- 26131119 TI - The association between the FABP2 Ala54Thr variant and the risk of type 2 diabetes mellitus: a meta-analysis based on 11 case-control studies. AB - Fatty acid binding protein 2 (FABP2) Ala54Thr gene polymorphism has been suggested to be associated with the increased risk of developing type 2 diabetes mellitus (T2DM), but some studies show the inconsistent result. The purpose of this meta-analysis is to assess the association between FABP2 Ala54Thr gene polymorphism variants and the T2DM. A total of 7095 subjects in 11 case-control studies were included in this meta-analysis. Under the allele model (T versus A), the pooled OR of Asian subgroup was 1.19 (95% CI = 1.06-1.32, P = 0.002). Under the recessive model (TT versus AA + AT), the pooled OR of Asian subgroup was 1.34 (95% CI = 1.05-1.71, P = 0.02). Under the dominant model (TT + AT versus AA), the pooled OR was 1.14 (95% CI = 1.03-1.27, P = 0.01) and when the analysis stratified by region, increased risks were identified among Asian (OR = 1.20, 95% CI = 1.05-1.38, P = 0.009). Under the codominant model (TT versus AA), no significant association was found. Under the codominant model (AT versus AA), the pooled OR was 1.14 (95% CI = 1.02-1.27, P = 0.02). It is indicated that the variant T allele carrier may increased the risk of T2DM and the risk is related to race. PMID- 26131120 TI - PTEN genomic deletion defines favorable prognostic biomarkers in localized prostate cancer: a systematic review and meta-analysis. AB - PTEN (10q23.3) is a negative regulator of the phosphatidylinositol 3-kinase (PIK3)/Akt survival pathway and a tumor suppressor frequently deleted in prostate cancer. PTEN genomic deletion is among the most common genetic aberrations in human prostate cancer. At present, the prognostic value of PTEN genomic deletion is unclear. We performed a systematic review and meta-analysis to clarify the association between PTEN genomic deletion and a higher Gleason score or a higher possibility of capsular penetration. A comprehensive, computerized literature search of PubMed was carried out until May 27, 2014. Studies were included according to specific inclusion criteria. Pooled hazard ratio was estimated using the fixed effects model or random effects model according to heterogeneity between studies. Seven eligible studies meeting the specific inclusion criteria were selected for further analysis; all were retrospective studies. Overall meta analysis demonstrated that PTEN genomic deletion was associated with a higher Gleason score (OR 0.319; 95% confidence interval: 0.153-0.666; P = 0.000) and a higher possibility of capsular penetration (OR 0.393; 95% confidence interval: 0.185-0.837; P = 0.015). None of the studies materially altered the original results and no evidence of publication bias was found. CONCLUSION: PTEN genomic deletion in operable localized prostate cancer indicates a higher Gleason score and a higher probability of capsular penetration, indicating a worse prognosis. Further studies should be conducted in order to investigate the effect of PTEN genomic deletion on clinical outcomes in different histological types of prostate cancer or its function in castration-resistant prostate cancer. PMID- 26131121 TI - Postoperative continuous wound infusion of ropivacaine has comparable analgesic effects and fewer complications as compared to traditional patient-controlled analgesia with sufentanil in patients undergoing non-cardiac thoracotomy. AB - OBJECTIVE: To compare the postoperative analgesic effects of continuous wound infusion of ropivacaine with traditional patient-controlled analgesia (PCA) with sufentanil after non-cardiac thoracotomy. METHODS: One hundred and twenty adult patients undergoing open thoracotomy were recruited into this assessor-blinded, randomized study. Patients were randomly assigned to receive analgesia through a wound catheter placed below the fascia and connected to a 2 ml/h ropivacaine 0.5% (RWI group) or sufentanil PCA (SPCA group). Analgesia continued for 48 h. Visual analogue scores (VAS) at rest and movement, Ramsay scores and adverse effects were recorded at 2, 8, 12, 24, 36 and 48 h after surgery. Three months after discharge, patient's satisfaction, residual pain and surgical wound complications were assessed. RESULTS: General characteristics of patients were comparable between two groups. There were no statistical differences in the VAS scores and postoperative pethidine consumption between two groups (P > 0.05). However, when compared with SPCA group, the incidences of drowsiness, dizziness and respiratory depression, ICU stay and hospital expenditure reduced significantly in RWI group (P < 0.05). Patients' satisfaction with pain management was also improved markedly in RWI group (P < 0.05). CONCLUSION: Continuous wound infusion with ropivacaine is effective for postoperative analgesia and has comparable effects to traditional PCA with sufentanil. Furthermore, this therapy may also reduce the incidences of drowsiness, dizziness, respiratory depression and decrease the ICU stay and hospital expenditure. PMID- 26131122 TI - Effect of dyslipidemia on intima-media thickness of intra- and extracranial atherosclerosis by regulating the expression of hsp70 in rabbits. AB - The aim of this study was to explore the effect of dyslipidemia on intima-media thickness (IMT) of Intra- and extracranial atherosclerosis by regulating the expression of heat shock protein 70 (HSP70) in rabbits. Twenty-seven male white rabbits were randomly divided into normal control group A, high fat group B and high fat + endothelial injury operation group C (each group was 9), we measured lipids and obtained tissues from different cerebral arteries including Bilateral common carotid artery (CCA), Internal carotid artery (ICA), middle cerebral artery (MCA) and vertebral artery (VA). Pathological analysis were done, western blot analysis was used to detect the expression of HSP70 in CCA and MCA. The Serum lipid levels were overall significantly increased at 12(th) week in Group B and Group C compared to normal control (P < 0.05); at 12(th) week, the IMT of CCA and MCA in group B and C were showed significant increment compared with Group A; the correlation between HDL/CHOL/LDL and IMT of different cerebral arteries are as follows: MCA > ICA > CCA > VA; between TG and IMT of different cerebral arteries: VA > ICA > MCA > CCA; the expression of HSP70 from MCA were increased compared with CCA in group B and group C (P < 0.05). Significant positive correlations were observed between hyperlipidemia and different cerebral arteries. Hyperlipidemia has more impact on IMT of intracranial cerebral arteries. The expression of HSP70 from intracranial cerebral arteries is significantly increased. The mechanisms underlied was speculated that might be involved in inhibiting the inflammatory via HSP70. PMID- 26131123 TI - Honokiol induces cell cycle arrest and apoptosis in human gastric carcinoma MGC 803 cell line. AB - OBJECTIVE: Gastric carcinoma is a malignant tumor that responds poorly to both chemotherapy and radiation therapy. In our study, we investigated the anti-cancer effect of honokiol, an active component isolated and purified from the Magnolia officinalis, in human gastric carcinoma MGC-803 cell line. METHODS: The cell viability was detected by the CCK8 assay. The cell apoptosis and cell cycle arrest were assessed by flow cytometer. The protein expression of cell cycle regulators and tumor suppressors were analyzed by western blotting. RESULTS: Treatment of human gastric carcinoma cells with honokiol induced cell death in a dose-and time-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that the proportion of apoptosis cells had gained when the cells were exposed to honokiol. Moreover, Cyclin B1, CDC2 and cdc25C were downregulated, and the expression of p-CDC2 and p-cdc25c was significantly upregulated upon honokiol treatment. P53 and p21 were significantly upregulated by honokiol treatment. Treatment of MGC-803 cells with honokiol significantly increased the pro-apoptotic Bax level and decreased the anti apoptotic Bcl-2 level. CONCLUSIONS: These results confirmed that honokiol could induce apoptosis and cell cycle arrest, the underlying molecular mechanisms, at least partially, through activation p53 signaling and downregulation CDC2/cdc25C expression. PMID- 26131124 TI - Systematic investigation into the role of intermittent high glucose in pancreatic beta-cells. AB - OBJECTIVES: Glucose fluctuation is suggested to be the leading cause of beta-cell damages. To determine how it induces beta-cell dysfunction, we systematically evaluated the effects of intermittent high glucose (IHG) in INS-1 rat pancreatic beta-cells on their proliferation activity, apoptosis, insulin secretion, reactive oxygen species (ROS), intracellular concentration of Ca(2+) ([Ca(2+)]i), and the PTEN expression as well as AKT phosphorylation. METHODS: Prior to the examinations, INS-1 cells were treated with normal glucose (NG, 11.1 mmol/L), sustained high glucose (SHG, 33 mmol/L), IHG (switching per 12 h in 11.1 mmol/l or 33 mmol/L), NG+alpha-lipoic acid (LA, pretreated with LA 12 h before exposure to NG), SHG+LA (pretreated with LA 12 h before being exposed to 33.3 mmol/L glucose) and IHG+LA (pretreated with LA 12 h before being cultured with IHG). The cells in each group were cultured with indicated concentrations of glucose for 3 days. The evaluations were carried out on the cell viability, apoptosis rate, insulin secretion, [Ca(2+)]i, ROS and the expressions of PTEN and p-AKT. RESULTS: The current study determined that IHG induces more apoptosis and significant increases of [Ca(2+)]i and intracellular ROS levels, compared to SHG and NG treatments to INS-1 cells. Moreover, IHG leads to more than 20% decrease on cell viability and over 50% reduction on insulin secretion (from 5.48+/-0.79 mIU/L to 2.51+/-0.58 mIU/L). The negative regulation of IHG on insulin signaling in beta cells is identified via western blot analysis with results of the elevated expression of PTEN and lowered phosphorylation levels of AKT post IHG treatment. While the pretreatment of the antioxidant LA can significantly suppress the above responses induced by high glucose treatment. CONCLUSIONS: This study demonstrated that IHG plays a detrimental role in the viability, expansion, and function of beta-cells. IHG could be more harmful to the INS-1 cells than the SHG treatment. The rate increase of apoptosis in beta-cells could be caused by the suppressed insulin signaling, which is resulted from the raised ROS level by abnormal glucose treatments. Undergoing oxidative stress induced by high glucose treatments, including SHG and IHG, might be an important player in mediating the injury process to beta-cells, concluded from the beneficial rescue by the antioxidant LA treatment. PMID- 26131125 TI - Early molecular responses of bone to estrogen deficiency induced by ovariectomy in rats. AB - OBJECTIVE: The study was performed to investigate bone deteriorations and the molecular responses of bone to early estrogen deficiency induced by ovariectomy (OVX) in rats. METHODS: The female rats were subjected to OVX (4 or 8 week) and sham (4 or 8 week) operation. All rats were killed 4 week or 8 week after the surgical operation. The biomarkers in serum and urine were measured. Hematoxylin & Eosin and tartate-resistant acid phosphatase staining were performed on paraffin-embedded bone sections. Expression of genes and proteins were analyzed by reverse transcription polymerase chain reaction and western blotting respectively. RESULTS: The OVX rats showed the decreased level of serum Ca and the increased level of urinary Ca excretion at 8 week post-OVX. The level of PTH and TRACP-5b increased at 4 and 8 week post-OVX. At both 4 and 8 week, FGF-23 was significantly lower in OVX rats than sham rats. The H&E staining showed remarkable bone abnormalities, including increased disconnections and separation of trabecular bone network in proximal metaphysis of tibia at OVX (4 and 8 week) group. In addition, the mRNA expression ratio of OPG/RANKL was reduced in the proximal tibia. The mRNA expression of MMP-9, CAII, EphA2 and ephrinA2, and the protein expression of EphA2 and ephrinA2 were markedly up-regulated in the proximal tibia. Moreover, the mRNA expression of TGF-beta, EphB4 and ephrinB2, and the protein expression of EphB4 and ephrinB2 were down-regulated in proximal metaphysis of tibia at OVX group. CONCLUSIONS: The endogenous estrogen deficiency was detrimental to bone, and the underlying mechanism was mediated, at least partially, through the local bone Eph/ephrin signaling pathway. PMID- 26131126 TI - Preventive effect of dexamethasone gelatin sponge on the lumbosacral epidural adhesion. AB - OBJECTIVE: This study aims to explore the preventive effect of dexamethasone gelatin sponge on the lumbosacral epidural adhesion in the laminectomy. METHODS: A total of 36 Wista rats were divided into A, B, C and D groups randomly. Dexamethasone was not used in group A, Dexamethasone was used in group B, Dexamethasone was not used in group C but covered with gelatin sponge, dexamethasone gelatin sponge was used in group D. 3 rats in each group were sacrificed at 4, 8 and 12 weeks after operation respectively and the wound was opened to observe the dural scar formation and the dura adhesion. Immunohistochemical technique was used for histology observation. The expressions of VEGF and VEGFR2 in the epidural scar and surrounding tissues were detected with western blotting and immunohistochemical methods. RESULTS: According to the Rydell score standard, there were different degree of adhesion formation in A, B and C groups while there was no obvious adhesion formation in D group. It was confirmed that the expressions of VEGF and VEGFR2 in group D were lower than that of the other groups. CONCLUSIONS: Dexamethasone gelatin sponge could significantly reduce the occurrence of epidural scar tissue hyperplasia and adhesion after laminectomy in rats, and its mechanism may be related to the decreased expression of VEGF and VEGFR2. PMID- 26131127 TI - Prolonged action potential duration in cardiac ablation of PDK1 mice. AB - The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) alphaMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis. PMID- 26131128 TI - Changes of amount and ultrastructure of interstitial cells of Cajal in rats with severe acute pancreatitis and their importance. AB - OBJECTIVE: To investigate the changes in the amount and ultrastructure of interstitial cells of Cajal (ICC) in rats with severe acute pancreatitis (SAP) and their importance. METHODS: A modified Aho method was employed to establish a SAP rat model. Laser scanning confocal immunofluorescence microscopy was employed to detect the amount of ICC, and transmission electron microscopy was employed for observation of ultrastructure of ICC and nerve-ICC-smooth muscle network. RESULTS: The amount of ICC reduced, the intercellular space of ICC was enlarged, cell processes reduced or were absent, cell morphology was irregular, and ICC had unclear borderline, reduced organelles, impaired organelles, nuclear shrinkage and deformation. The junctions between ICC and between ICC and smooth muscle cell/nerve reduced, and the network-like structure was disrupted. CONCLUSION: In SAP, ICC reduces, with disrupted ultrastructure, and the integrity of network among intestinal nerve, ICC and smooth muscle is impaired, both of which may affect the intestinal functions. PMID- 26131129 TI - LncRNA MALAT1 overexpression is an unfavorable prognostic factor in human cancer: evidence from a meta-analysis. AB - Long non-coding RNAs (lncRNAs) have been suggested to serve as an important role in tumor development and progression. The aim of this study was to analyse the association between lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and cancer patients' overall survival. We systematically and carefully searched the studies from electronic databases and seriously identified according to eligibility criteria. The correlation between lncRNA MALAT1 expression and overall survival in human cancers was evaluated through Review Manager. A total of 8 studies which included 792 cancer patients were included in the final analysis. Meta-analysis showed that lncRNA MALAT1 overexpression was correlated with a poor overall survival and the pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) was 1.94 (95% CI 1.59-2.38). From subgroup analyses, we present evidence that lncRNA MALAT1 overexpression was an unfavorable prognostic factor for patients' overall survival in non-small cell lung cancer and pancreatic cancer, the pooled HRs (95% CI) were 1.86 (95% CI 1.27-2.73) and 1.78 (95% CI 1.30-2.44), respectively. In conclusion, lncRNA MALAT1 is a potential prognostic factor in human cancers. PMID- 26131130 TI - Cholangiocarcinoma: prognostic factors after surgical resection in China. AB - OBJECTIVE: The management of cholangiocarcinoma remains a challenge due to poor prognosis. The aim of this study was to identify the influencing factors related to outcome of patients with cholangiocarcinoma. METHODS: From January 1999 to January 2009, 169 cases of cholangiocarcinoma undergoing surgery were analyzed retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis. RESULTS: The 1-, 3- and 5-year survival rates of patients after resection were 52.6%, 32.4%, 11.7%, respectively. Univariate analysis showed that CEA, lymph node metastasis, surgical margin, AJCC staging, tumor differentiation and adjuvant chemotherapy were prognostic impacts. The difference was statistically significant (P<0.05). Cox multivariate analysis showed that CEA, lymph node metastasis and surgical margin are three independent prognostic factors. CONCLUSION: Radical resection is the key to improve the long term survival rate of cholangiocarcinoma. Important predictive factors related to poor survival are CEA, lymph node metastasis and surgical margin. PMID- 26131131 TI - Association between aldosterone synthase (CYP11B2) -344C/T polymorphism and atrial fibrillation among Han and Kazak residents of the Xinjiang region. AB - OBJECTIVES: Atrial fibrillation (AF) is one the most common and complex types of clinical arrhythmia syndromes. In recent years, an association between CYP11B2 gene polymorphisms and atrial myocardial fibrosis has received a significant amount of attention. This study explores the relationship between CYP11B2 gene 344C/T polymorphism and AF among Kazak and Han residents in the Xinjiang region and further clarifies the molecular mechanisms of atrial fibrillation. METHODS: The study is a case-control study using traditional methods. We selected 156 Kazak and 203 Han patient cases in the Xinjiang region who had non-valvular atrial fibrillation as well as 307 Kazak and 418 Han cases of non-AF patients as a control group. Blood samples were collected, and DNA was extracted from the peripheral blood samples. The presence of the CYP11B2 gene-344C/T polymorphism was determined using polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP). Differences in the genotypes and allele distributions among the 2 groups were compared using Statistical Package for Social Science (SPSS) 17.0 statistical software. Student's t test, the chi-squared test and logistic regression methods were used for the data analysis. RESULTS: The genotypes of both ethnic groups followed a Hardy-Weinberg genetic equilibrium distribution. The 2 patient groups, compared with their respective control groups, showed significant dominant models in CYP11B2 gene-344C/T polymorphism genotype frequency and B1 allele frequency (P<0.05). The frequencies of the CYP11B2 gene-344C/T polymorphism in the Kazak patient group were higher compared with the control groups (P<0.05). The frequencies of the CYP11B2 gene-344C/T polymorphisms in the Han patient group was also higher compared with the control group (P<0.05). Logistic regression analysis showed that the frequencies of the CYP11B2 gene-344C/T genotypes were significantly different between the Kazak and Han patient groups and the control groups. CONCLUSION: CYP11B2 gene -344C/T polymorphism is associated with AF. PMID- 26131132 TI - The SNP rs4804611 in ZNF627 gene and the risk of myocardial infarction: a meta analysis. AB - A single nucleotide polymorphism (rs4804611) in zinc finger protein 627 (ZNF627) gene has been demonstrated to be associated with the susceptibility to myocardial infarction (MI), but the results are inconsistent. Therefore, a meta-analysis of eligible studies reporting the association between rs4804611 and MI was carried out to enhance the reliability of published results. A systematic literature search was performed using PubMed, Web of Science, Cochrane Library to search English articles concerning the relation between rs4804611 and MI up to January, 2015. Summary odds ratios (OR) and 95% confidence interval (CI) were used to evaluate the risk of MI. The heterogeneity and publication bias of this study were also evaluated. Five eligible studies involving 11639 subjects (6299 patients and 5340 healthy controls) were included in this meta-analysis. Overall, the results indicated that rs4804611 polymorphism was associated with the risk of MI (GG vs. AA/AG: OR = 0.833, 95% CI = 0.704-0.985, P = 0.033). Furthermore, subgroup analyses also showed that rs4804611 polymorphism was associated with the risk of MI in Caucasian (GG vs. AA/AG: OR = 0.839, 95% CI = 0.704-0.999, P = 0.048). In conclusion, our meta-analysis suggests that the rs4804611 polymorphism in ZNF627 gene is associated with the risk of MI. However, further large scale case-control studies with rigorous design should be conducted to confirm the conclusion in the future. PMID- 26131133 TI - Effect of valsartan on ACAT-1 and PPAR-gamma expression in intima with carotid artery endothelial balloon injury in rabbit. AB - OBJECTIVE: To study the effect of valsartan on ACAT-1 and PPAR-gamma expression after vascular endothelial balloon injury in intimal hyperplasia process. METHODS: 24 male New Zealand white rabbits were randomly divided into three groups with 8 in each group. CONTROL GROUP: rabbits were fed with normal diet; Balloon injury group: rabbits were fed with 0.5% cholesterol, 5% lard rabbit feed; balloon injury + valsartan group, rabbits were fed with 0.5% cholesterol, 5% lard rabbit feed added with 10 mg/(kg.d) valsartan gavage. RT-PCR and Western blotting method were used to detect the carotid ACAT-1, PPAR-gamma mRNA and protein expression after 8 weeks of feeding. RESULTS: In carotid artery balloon injury group, vascular smooth muscle cells (VSMC) proliferation and intimal hyperplasia were significantly higher 14 d after endothelial injury. In 14 days valsartan treatment group VSMC proliferation and intimal hyperplasia were lighter than the surgery group. Compared with the control group, ACAT-1, PPAR-gamma mRNA and protein were significantly increased in balloon injury group and valsartan group (P < 0.01 or P < 0.05); the expression of ACAT-1 mRNA and protein were significantly lower in valsartan group and balloon injury group (P < 0.01 or P < 0.05). The expression of PPAR-gamma mRNA and protein in valsartan group expression was significantly higher than that in the balloon injury group (P < 0.05). The expression level of ACAT-1 and PPAR-gamma mRNA in balloon injury group and valsartan group showed negative correlation (P < 0.05). CONCLUSION: The expression of ACAT-1, PPAR-gamma mRNA and protein content were significantly increased in intimal hyperplasia process after vascular endothelial balloon injury. The effect of valsartan suppressed intimal hyperplasia correlated with the expression of down-regulated ACAT-1 and up-regulated PPAR-gamma. PMID- 26131134 TI - MicroRNA-222 promotes human non-small cell lung cancer H460 growth by targeting p27. AB - Two highly homologous microRNAs (miRNAs, miRs), miR-222 and miR-221, act as a cluster in cellular regulation. We have previously reported that miR-221 promoted the growth of human non-small cell lung cancer cell line H460. However, the role of miR-222 in regulating the growth of H460 is unclear. H460 cells were transfected with miR-222 mimics, inhibitors or their negative controls and their effects were confirmed by Real-time quantitative reverse transcription polymerase chain reactions (qRT-PCRs). Cell viability was assessed by Cell Counting Kit-8 (CCK-8) while cell proliferation was determined by 5-Ethynyl-2'-deoxyuridine (EdU) assay. P27 and P57, two putative targets of miR-222, were checked by qRT PCRs. We found that miR-222 overexpression increased cell viability and proliferative rate in H460 cells while opposite effects were obtained by down regulation of miR-222. P27 but not P57 was identified as a potential target of miR-222 in H460 cells as P27 was negatively regulated by miR-222 in the protein level. In summary, the present study indicates that miR-222 controls the growth of H460 likely by targeting P27. Inhibition of miR-222 might be a novel therapy for human non-small cell lung cancer. PMID- 26131135 TI - Gastric-jejunum pouch side-to-end anastomosis: a novel and safe operation of gastrojejunostomy for preventing reflux gastritis. AB - PURPOSE: This study aims to introduce a simple operation method of gastrojejunostomy for preventing reflux esophagitis --gastric-jejunum pouch side to-end anastomosis. METHODS: Based on Billroth II anastomosis (Billroth II) method, we designed a new technique of anastomosis between stomach wall and jejunal pouch. The technique was named gastric-jejunum pouch side-end anastomosis. We retrospectively analyzed the clinical data which was collected from March 2012 to February 2014. Among all the recruited 66 patients, 51 gastric cancer patients and 7 pyloric obstruction patients were implemented with hand assisted laparoscopic distal gastrectomy plus D2 lymph node dissection. The remaining 8 patients were malignant pyloric obstruction; they were treated with small exploratory incision on the upper abdomen and distal gastric partial transection. All the patients were treated with gastric-jejunum pouch side-to-end anastomosis. RESULTS: The surgical incision was small, the operative time was short, their bleeding volume was little, the recovery time of the bowel function and hospitalization time was relatively short. Postoperatively, there was neither mortality and gastroparesis, nor anastomotic leakage and jejunal pouch leakage. Minor postoperative complications were detected followed up for 12 months, no acid reflux and reflux esophagitis symptoms was reported. CONCLUSIONS: Gastric jejunum pouch side-to-end anastomosis is a simple operation technique with highly surgical safety. PMID- 26131136 TI - Protective effects of heparin on endothelial cells in sepsis. AB - OBJECTIVE: This study aims to observe the protective effects of heparin on endothelial cells in sepsis and explore the involved signal pathway regulated by heparin. Methods Human vascular endothelial cells were treated by TNFalpha in vitro to simulate the inflammatory environment when sepsis occurred. They were intervened by heparin and the expression levels of soluble thrombomodulin (sTM) and serum activated protein C (APC) were detected by ELISA, the regulatory mechanism of heparin improving vascular endothelial cells injury induced by TNFalpha was detected by Western Blotting method, the methylation of histone in the gene promoter region of endothelial nitric oxide synthase (eNOS) and monocyte chemotactic protein-1 (MCP-1) were detected using chromatin immunoprecipitation method. Results Heparin could inhibit the secretion of sTM and APC protein and the expression of MCP-1 gene which involved in NF-kappaB signal pathway. Conclusions Heparin could protect vascular endothelial cells from injury induced by TNFalpha and sepsis, the mechanisms were related with the effects of heparin on the histone methylation of promoter region and the regulation of heparin on the MAPK and NF-kappaB signal pathways. These results provide a theoretical basis for the application of heparin in the prevention and treatment of vascular disease related with sepsis. PMID- 26131137 TI - The role of leptin in the ventricular remodeling process and its mechanism. AB - OBJECTIVE: This study aims to explore the role of leptin in the ventricular remodeling process and its mechanism in the diabetic rats' model. METHODS: The diabetic SD rats model induced by streptozotocin was established. The SD rats were randomly divided into 4 groups: control group (20 rats treated with citric acid/sodium citrate buffer); M0 group (10 rats treated with physiological saline); M1 group (10 rats treated with 50 MUg/kg LP); M2 group (10 rats treated with 100 MUg/kg LP). Ang-II was detected by ELISA. The expression levels of LP and Ob-Rb were detected by RT-PCR. MAPK phosphorylation changes were detected by western blotting. Myocardial morphology was observed. RESULTS: Compared with control group, the blood glucose concentration and Ang-II significantly increased in diabetic model groups (P < 0.01) and body weight decreased (P < 0.05). The expression levels of LP and Ob-Rb increased and heart function decreased in diabetic model groups. CONCLUSIONS: LP may be involved in the myocardial cell hypertrophy through the neuroendocrine system and associated with the JAK-STAT, Ras-Raf-MEK-MAPK and PI-3K signaling pathway, which provides a new concept for the pathogenesis of cardiac hypertrophy. PMID- 26131139 TI - Effect of hydrogen injected subcutaneously on testicular tissues of rats exposed to cigarette smoke. AB - Smoking is one of the most common reasons inducing reactive oxygen species in semen. High concentration of active oxygen will cause decrease of sperm density and viability and induce oxidative injury of sperm DNA which has become the hot spot in male infertility. Although hydrogen was found to be an effective remover of active oxygen in liver, heart, kidney and brain, the same effect has not been discussed in reproductive system. The aim of this study was to investigate the protective effect of hydrogen against cigarette smoke-induced damage in rat reproductive system. Adult male Wistar rats were randomly divided into four groups to conduct this experiment, results showed that rats in SK+HSI group (passive smoking and hydrogen subcutaneous injection group) exhibited larger amount of sperm count, smaller sperm deformation rate, higher levels of testosterone and SOD in serum and testis, lower levels of MDA in testis and less morphologic abnormalities compared to SK+NSI group (passive smoking and nitrogen subcutaneous injection group). As a consequence, we concluded that injected subcutaneously exerted protective effects on reproductive system injury of male rats exposed to cigarette smoke through inhibiting oxidative damage. PMID- 26131138 TI - Titanium mesh cage fracture after lumbar reconstruction surgery: a case report and literature review. AB - Titanium mesh cage (TMC) was introduced recently to provide anterior structural support and interbody fusion without the need to harvest bone from the iliac crest. Because of its good mechanical behavior and satisfactory clinical outcomes, TMC is commonly used for lumbar burst fractures. Here, we present a female patient who underwent a posterior-anterior L4 corpectomy with TMC placement and developed a cage fracture after 42 months. The patient refused the revision surgery and asked for conservative treatment. At the 3-month follow-up, she reported doing well, with no complaints of back pain or leg pain. There were three cases of TMC fracture have been previously reported in the literature. Only one patient performed a revision surgery with an expandable titanium cage, and all this three patients experienced a good outcome during the follow-up period. TMC fracture is a rare complication of spinal surgery. Close observation or surgical treatment should be considered to improve patient outcomes. Although cage placement, instability, subsidence, and both stress shielding and necrotic bone in the cage appear to play key roles in the pathogenesis of this rare complication, the exact mechanism of this condition remains undetermined. PMID- 26131140 TI - Raloxifene suppress proliferation-promoting function of estrogen in CaSKi cervical cells. AB - Raloxifene has demonstrated anti-estrogen activity in reproductive organs and tissues, but there are very few related studies in cervical cells. The aims of this study is to explore the function of raloxifene in CaSKi cervical cells. We examined the effects of raloxifene on cervical cancer cells exposed to estrogen. The effect of Raloxifene on cell growth, apoptosis was detected. The human papillomavirus (HPV) 16 E6E7 transcription in cervical cell line CaSki cells exposed to 17-estradiol was also examined. Apoptosis was measured by endonucleolytic degradation of DNA. HPV 16 E6E7 was measured by northern analysis. The results indicated that raloxifine inhibits estrogenic promotion activity on growth of CaSki cells. Raloxifene suppresses the proliferation promotion activity of estradiol in CaSki cells. Raloxifene suppresses the stimulation effect of estradiol on HPV 16 E6E7 transcription in CaSki cells. In conclusion, raloxifene inhibit the CaSki cells proliferation induced by estradiol, which suggests that raloxifine also has anti-estrogen activity in cervical cells. PMID- 26131141 TI - Surgical management of medulla oblongata hemangioblastomas in one institution: an analysis of 62 cases. AB - OBJECT: Hemangioblastomas of the central nervous system are highly vascularized benign tumors. When the tumors are located in the medulla oblongata, intraoperative bleeding can make the surgical procedure very difficult. Preoperative embolism has been performed in cases of hemangioblastoma in recent decades. However, the complications of the embolization can result in fatal consequences, especially when the lesions are located in the brainstem. In recent years, selectively blocking the suspicious feeding arteries of the tumors during operation in conjunction with intraoperative neurophysiological monitoring has been performed in the Department of Neurosurgery at the West China Hospital. The purpose of this study is to review all cases that underwent this surgical management and to evaluate their outcomes. METHOD: Between 2003 and 2014, 62 patients (36 female and 26 male, mean age 35.6 years) underwent microsurgery resection of 67 medulla oblongata hemangioblastomas. The suspicious feeding arteries were identified preoperatively by CTA or DSA. During the operation, the suspicious feeding arteries were blocked selectively by motor evoked potential (MEP) and somatosensory evoked potential monitoring (SEP). Based on the retrospectively review of the clinical records and outpatient long-term follow-up visits, their clinical courses were analyzed. Functional outcomes were evaluated according to the classification of McCormick and the Karnofsky Performance Scale. RESULT: The maximum tumor diameter ranged from 0.8 to 5.1 cm (mean, 2.9 cm). Total tumor resection was achieved in 60 patients. Sixty-one tumors were removed en bloc, and the other six were resected in a piecemeal fashion. The mean follow up period was 47 months. During the follow-up period, 34 patients remained neurologically stable, 27 patients recovered to a better status and 16 patients developed new transient neurological dysfunction. One patient died. Karnofsky performance scale scores were 100 in 14 patients (22.9%), 90 in 18 patients (29.5%), 80 in 24 patients (39.3%) and 40 to 70 in 5 patients (8.2%). Seventeen cases were associated with von Hippel-Lindau (VHL) disease. In all the cases, tumor recurrence was observed during follow-up in only 2 patients. CONCLUSION: This study suggests that safe and effective surgical management of medulla oblongata hemangioblastomas can be achieved for most patients, even without preoperative embolization. With the assistance of intraoperative MEP and SEP, mistaken cutting of the vessels that feed the brainstem can be avoided. With improved microsurgical techniques, intraoperative neurophysiological monitoring and a better understanding of the vascular pattern of tumors, total and en bloc microsurgical removal can be performed with low mortality and favorable prognosis of neurological function. PMID- 26131142 TI - Matrine regulates immune functions to inhibit the proliferation of leukemic cells. AB - AIMS: To investigate the roles of matrine in regulating immune functions and its effect on the proliferation of leukemic cells. METHODS: Human leukemia K562, OUN 1, HL-60, U937, K562/AO2 cell lines and primary leukemic cells were used to detect the NKG2D ligands (NKG2DL) expression such as MICA/B, ULBP-1, ULBP-2, ULBP 3, and NK cells receptor NKG2D, CD158a, CD158b were detected by flow cytometry. Cell cytotoxic activity of human NK cells and CIK cells against K562 leukemia cells was detected using CFSE/PI double staining. Pro-inflammatory cytokines and adhesion molecules in K562 or NK cells supernatant after matrine treatment were detected. RESULTS: Matrine could upregulate the expression of NKG2DL on leukemic cell lines, and primary leukemic cells and enhance the NK and CIK cytotoxicity targeted to K562 cells. After matrine treatment, pro-inflammatory cytokines and adhesion molecular such as IL-6, IL-1, IL-2, IL-4, IL-5, GRO and TNF-alpha in K562 cells supernatant were significantly decreased (P < 0.05). Flow cytometry analysis showed that the NKG2D expression was up-regulated significantly as well as the CD158a and CD158b expression decreased after treatment with different concentration of matrine in a dose-dependent manner in K562 cells. A significant decrease of supernatant concentrations of IL-1alpha, IL-5, IL-6, IL-10, IFN gamma, GRO and TNF-alpha in NK cells was also observed after exposure to the matrine. CONCLUSION: Matrine regulates immune functions to inhibit the proliferation of leukemic cells. PMID- 26131143 TI - Cytokine-induced killer cells combined with dendritic cells inhibited liver cancer cells. AB - OBJECTIVES: To investigate the prognosis of advanced liver cancer patients treated with CIK-DCs and the mechanism of apoptosis of HEPG 2 cells. METHODS: 67 patients were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were separated, of which adherent PBMCs used granulocyte 2 macrophage colony2 stimulating factor (GM2CSF), tumor necrosis factor 2alpha (TNF2alpha), and interleukin 24 (IL24) to induce DCs, which were sensitized with antigen of autologous or exogenous cancer cells to obtain Ag-DCs; suspended PBMCs used interferon 2gamma (IFN2gamma), IL-2, and CD 3 monoclonal antibody (CD3mAb) respectively, to induce CIK cells. DCs and CIK cells were cultured together. Flow cytometry was used to detect the phenotypes of DCs and CIK cells, and the blood retransfused into patients. Western blot and flow cytometer were used to analyze the growth cycle of HepG 2 cells and the expression of BAX and PCNA. RESULTS: No patients underwent complete remission, 5 obtained partial remission and 29 had stable disease. Of the 31 patients whose lesions could not be evaluated, 17 received effective treatment, showing that the immune response was enhanced. In vitro laboratory experiments revealed that DC-CIK cells markedly affected the growth cycle of HepG 2 cells. Analysis showed that DC-CIK cells enhanced the gene expression of BAX and inhibited the activity of PCNA. CONCLUSIONS: Co-cultured DCs and CIK cells inhibit the proliferation and migration of liver cancer cells by down-regulating PCNA and up-regulating BAX. This approach may be an effective method to treat advanced liver cancer. PMID- 26131144 TI - Expression profile and clinical significance of miRNAs at different stages of chronic hepatitis B virus infection. AB - OBJECTIVE: To study the expression profile and clinical significance of microRNAs (miRNAs) at different stages of chronic hepatitis B virus (HBV) infection. METHODS: The miRNA expression profiles of peripheral blood mononuclear cells (PBMCs) at different stages of chronic HBV infection were screened using miRNA microarray and validated using real-time quantitative polymerase chain reaction (qPCR). RESULTS: Significant differences in miRNA expression profiles of PBMCs were observed between patients in IA and IT phases of CHB. Expression was significantly down-regulated in the former but up-regulated in the latter group. No significant differences in inactive hepatitis B surface antigen carriers were observed. Changes in expression of six miRNAs determined by real-time qPCR were consistent with those determined by microarray. Areas under the receiver operation characteristic curve of the six miRNAs distinguishing immune tolerance and clearance of chronic HBV infection were 99.4%, 98.4%, 96.7%, 100%, 100%, and 99.6%. Positive correlation was found between the levels of hsa- miR-146a and ALT (r = 0.56, P < 0.01) while negative correlation was found between the levels of hsa-miR-548ah-5p and HBV DNA (r = -0.73, P < 0.01). CONCLUSIONS: Abnormal expression of miRNAs and the resulting gradual decline in the various immune states of patients with chronic HBV infection may play important roles in maintenance of the immune homeostatic mechanisms of chronic HBV infection. Hsa miR-548ah-5p, hsa-miR-3191-5p and hsa-miR-4711-3p can be used as potential molecular markers to distinguish among different stages of chronic HBV infection. PMID- 26131145 TI - Relation of behavior problems with findings of cranial diffusion tensor MRI and MR spectroscopy in autistic children. AB - PURPOSE: To investigate any relation of behavior problems with cranial Diffusion Tensor Imaging (DTI) and Magnetic Resonance Spectroscopy (MRS) findings in autism spectrum disorders. MATERIALS AND METHODS: A total of 20 males children (12 autistic patients and 8 healthy controls) was examined by cranial DTI and MRS. The Aberrant Behavior Checklist (ABC) was used to calculate the irritability, lethargy-social withdrawal, stereotypic behavior, hyperactivity, and speech disorder scores for each patient. The results of MRS and DTI were evaluated together with the ABC scores. RESULTS: Fractional anisotropy (FA) values demonstrated significant decreases in the left frontoparietal white matter, anterior limb of the right internal capsule, and left middle cerebellar peduncle as the behavior problem scores elevated (P < 0.05). With the exception of social withdrawal, as the behavior problem scores increased, metabolite levels increased, as well. CONCLUSION: The positive correlation between the MRS findings, behavior problem scores, and metabolite levels suggests the presence of a dysfunction leading to hypo and hyper neuronal function in various locations. Reduced FA values in DTI and negative correlation of behavior problems with FA values in the contralateral hemisphere, may indicate reduced myelination and abnormal axonal organization. PMID- 26131146 TI - Proteomic profiling of posterior longitudinal ligament of cervical spine. AB - OBJECTIVE: To identify putative biomarkers for ossification of posterior longitudinal ligament (OPLL). MATERIAL AND METHODS: Proteomic analysis was performed in 4 ligament samples from OPLL patients and healthy controls. RT-PCR was used to further verify the proteomic analysis results. RESULTS: A total of 50 differentially expressed spots were detected in 2-D electrophoresis between the two groups. In protein/peptide analysis, 21 proteins or peptides were finally identified. Besides 13 hematic proteins and 2 unknown proteins, 6 other proteins were differentially expressed. Among them, carbonic anhydrase I, NAD(P) dependent steroid dehydrogenase-like, billiverdin reductase B and alpha-1 collagen VI were down-regulated, while osteoglycin and nebulin-related anchoring protein were up regulated. The results of NAD(P) dependent steroid dehydrogenase-like, alpha-1 collagen VI and nebulin-related anchoring protein were validated by RT-PCR. CONCLUSION: These differentially expressed proteins could play a role in the onset and progression of OPLL. PMID- 26131147 TI - Recent progress in the diagnosis and treatment of posterior tibial plateau fractures. AB - The posterior tibial plateau fracture is drawing increasing attention from orthopedists in recent years with the popularity of CT. However, due to the particular and severity of posterior tibial plateau fracture, there is still controversy in its classification and treatment. It is very difficult to achieve the ideal reduction and fixation by conventional techniques and approaches. The modified posterior approach is favorable for posterior tibial plateau fracture, but disadvantages remain. Recently, the lateral approach is applied by doctors. It is ideal for treatment of posterior tibial plateau fracture. Because of the complexity of local anatomical structure, the operative management of posterior tibial plateau fractures is a contentious issue as revealed in the recent surge of published literature addressing the surgical approach. This review mainly summaries the diagnosis, classification and surgery of the posterior tibial plateau fractures. PMID- 26131148 TI - Effect of neoadjuvant chemotherapy on sevoflurane MAC-BAR value of patients undergoing radical stomach carcinoma surgery. AB - OBJECTIVE: To determine the minimum alveolar concentration (MAC) of sevoflurane required for 50% blockade of the adrenergic response (BAR) to surgical incision in patients treated with neoadjuvant chemotherapy prior to radical gastrectomy. PATIENTS AND DESIGN: Forty-four patients were selected for this study. Patients with preoperative neoadjuvant chemotherapy comprised the NC group (n = 22) and patients without preoperative neoadjuvant chemotherapy were included as the C group (n = 22). Patients in the NC group were treated with two cycles of 14-day neoadjuvant chemotherapy with combination of oxaliplatin and Gio, and underwent surgery 3 weeks later. Patients in the C group received no chemotherapy prior to surgery. A sequential allocation method was employed to determine the MAC-BAR for each group. The initial end-tidal concentration of sevoflurane was set as 3% for both the NC and C groups. Sympathetic responses to surgical incision were evaluated 6 times by measuring the heart rate (HR) and mean arterial blood pressure (MAP) at 1 min intervals before (T1, T2, T3) and after (T4, T5, T6) skin incision, and used to adjust the end-tidal sevoflurane concentrations for each patient. More than a 15% increase in MAP or HR after incision was scored as a positive response. MAIN RESULTS: The HR and MAP levels measured pre- (T1) and post-incision (T6) were significantly lower than base line values at admission in both groups, but without statistical difference between the groups. The MAC-BAR value of sevoflurane was 2.2% in the NC group and 3.0% in the C group (P < 0.05). CONCLUSIONS: Neoadjuvant chemotherapy reduced the MAC-BAR value of sevoflurane in gastric cancer patients by enhancing the inhibitory effect of sevoflurane on the stress response. PMID- 26131149 TI - Sustained improvement of quality of life for nasopharyngeal carcinoma treated by intensity modulated radiation therapy in long-term survivors. AB - IMRT has achieved an excellent survival and less radiation-induced sequelae with improvement of QoL within 2 years compared to conventional radiotherapy for NPC. Whether IMRT could sustained decrease incidence of late sequelae and improve QoL further for long-term survivors remained unknown. 176 patients from Aug. 2002 to Jun. 2009 were retrospectively analyzed. Radiation-related toxicities were graded according to both the Acute and the Late Radiation Morbidity Scoring Criteria of the EORTC/RTOG; QoL was assessed by the EORTC QLQ-C30 and H&N35 questionnaires at 5 and 8 years. The 5-year overall survival rate was 68.2% with a median follow-up time of 86 months. The most common radiation-related acute and late toxicity was xerostomia, the incidence of Grade >= 1 xerostomia was 90.3%, 84.1%, 75.9% and 59.2%, respectively at acute, 6 months, 2 years and 5 years. Statistical analysis indicated a close relationship between 5 years with 6 months and 2 years for patients who had >= 3 xerostomia at acute phase (r = 0.538 for late xerostomia at 6 months with 5 years, r = 0.732 for 2 years with 5 years); Sustained amelioration of other sequelae was also observed; QoL questionnaires at 5 years showed a significant improvement of most items and got stable between 5 to 8 years. IN CONCLUSION: IMRT could sustain reduce late radiation sequelae and improve QoL for long-term survivors over time; Patients with severe acute xerostomia (>= grade 3) would have a significant correlation of mitigatory xerostomia during the late follow-up time. PMID- 26131150 TI - Interferon-gamma polymorphism and hepatocellular carcinoma susceptibility: a meta analysis. AB - BACKGROUND: Interferon-gamma (IFN-gamma) was first defined as an antiviral agent with potent antitumor effects in 1957 and this is supported by much subsequent research. IFN-gamma rs2430561 polymorphism was found to increase IFN-gamma production involved in the regulation of immune system. Previous studies of rs2430561 genotypes and hepatocellular carcinoma (HCC) susceptibility have produced inconsistent results. We thus summarized all epidemiologic and molecular data and carried out a meta-analysis to evaluate the effects of this functional polymorphism on HCC incidence. METHODS: Human hospital- or population-based studies were identified by searching multiple databases (BIOSIS, Embase, PubMed, Web of Science, Chinese Biomedical Literature database). Six studies were selected for the meta-analysis. Crude ORs was calculated assuming the allele, homozygote, heterozygote, dominant and recessive model. The stability and reliability of the combined results were examined by using sensitivity analysis and publication bias tests. RESULTS: Meta-analysis under the allele model showed that the T allele compared with the A allele showed a moderately but nonsignificantly increased risk of HCC (OR = 1.12, 95% CI = 0.92-1.35). Analyses under the remaining models revealed no evidence of a significant association. In subgroup analysis by infection type, summary ORs suggested no significantly elevated risk of HBV-infected HCC in relation to the allele or genotypes of rs2430561 polymorphism. The combined results were reliable according to sensitivity analysis and publication bias tests. CONCLUSION: We found no strong evidence supporting a statistically significant association between IFN-gamma rs2430561 polymorphism and HCC susceptibility. PMID- 26131151 TI - Association of matrix metalloproteinase-1 -519A/G polymorphism with acute coronary syndrome: a meta-analysis. AB - Matrix metalloproteinase-1 (MMP-1) has been demonstrated to play an important role in the development and progression of acute coronary syndrome (ACS). Recent studies have shown that MMP-1 -519A/G (rs1144393) polymorphism is associated with the susceptibility to ACS. However, published studies showed inconsistent results. Therefore, a meta-analysis of eligible studies reporting the association between -519A/G polymorphism and ACS was carried out. A systematic search was conducted using PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure and Chinese Wan Fang database. Six eligible studies involving 5670 subjects (2868 ACS patients and 2802 healthy controls) were included in this meta-analysis. Overall, this meta-analysis showed a significant association between the rs1144393 polymorphism and ACS (A vs. G: OR = 1.385, 95% CI = 1.019-1.882, P = 0.037; AA vs. AG/GG: OR = 1.547, 95% CI = 1.002-2.389, P = 0.049). Furthermore, subgroup analyses also displayed significant associations between MMP-1 rs1144393 polymorphism and susceptibility to acute myocardial infarction (AA/AG vs. GG: OR = 1.275, 95% CI = 1.016-1.600, P = 0.036) or unstable angina pectoris subjects (A vs. G: OR = 2.128, 95% CI = 1.696-2.670, P < 0.001; AA vs. GG: OR = 2.933, 95% CI = 1.339-6.421, P = 0.007; AA vs. AG/GG: OR = 2.477, 95% CI = 1.457-4.211, P = 0.001). But we found no significant association between the -519A/G polymorphism and ACS either in Asian or Caucasian. In conclusion, our meta-analysis suggests that MMP-1 -519A/G polymorphism was associated with the susceptibility to ACS. However, further large scale case control studies with rigorous design should be conducted to confirm above conclusions in the future. PMID- 26131152 TI - miR-15a/16 are upreuglated in the serum of neonatal sepsis patients and inhibit the LPS-induced inflammatory pathway. AB - Infection in neonates, particular the neonatal sepsis continues to be a global problem with significant morbidity and mortality. The diagnosis of neonatal sepsis is complicated by nonspecific clinical symptomatology, a high-false negative rate, and a delay in obtaining blood culture results. MicroRNAs (miRNAs) have recently been used as finger prints for sepsis, and have been validated to be potential sepsis biomarker recently. In the present study, we investigated the level of several miRNAs, such as miR-15a, miR-16, miR-15b, and miR-223, which have been identified as a biomarker in adult sepsis, in neonatal sepsis patients, and then we analyzed the association of miR-15a/16 with the patient prognosis. Results demonstrated that the level of miR-15a/16 was up-regulated in neonatal sepsis patients than in normal neonatal subjects; however, no statistical difference was disclosed in the miR-15b and miR-223 level between two groups. And the ROC analysis indicated the miR-15a and miR-16 were potent fingerprints for diagnosing neonate sepsis. In order to explore the miR-15a/16 function on the lipopolysaccharide (LPS)-induced inflammatory pathway, the mice macrophage RAW264.7 cells were transiently transfected with miR-15a/16 mimics. And it was demonstrated that the miR-15a/16 transfection down-regulated the Toll-like receptor 4 (TLR4) and Interleukin-1 receptor-associated kinase 1 (IRAK-1) transcription level with a statistical difference in the LPS treated cells. And the suppression capability of miR-15a/16 on the expression of TLR-4 and IRAK-1 were evaluated by western blot. Thus, in present study, we identified miR-15a/16 as potential biomarker for the diagnosis and prognosis of neonatal sepsis, and the upregulated miR-15a/16 downregulated the LPS-induced inflammatory pathway. PMID- 26131153 TI - Comparison of dexmedetomidine and propofol used for drug-induced sleep endoscopy in patients with obstructive sleep apnea syndrome. AB - Backround: Surgical operations are alternative treatments in persons with Obstructive Sleep Apnea Syndrome who cannot tolerate continuous positive airway pressure therapy. Drug-Induced Sleep Endoscopy is a method with which somnolence is pharmacologically induced and collapse is evaluated through nasal endoscopy in patients with Obstructive Sleep Apnea Syndrome. AIMS: We aimed to evaluate efficiency of dexmedetomidine or propofol used for sedation in patients undergoing drug-induced sleep endoscopy. METHODS: A total of 40 patients aged between 18 and 65 years old in the ASA STATUS I-II group were included in the study. After premedication with midazolam 0.05 mg/kg intravenously, patients were randomly divided into two groups and administered intravenous (iv) propofol with the loading dose of 0.7 mg/kg for 10 minutes, followed 0.5 mg/kg/h infusion (Group P); or dexmedetomidine with the loading dose of 1 mcg/kg for 10 minutes, followed by 0.3 mcg/kg/h infusion (Group D). Haemodynamic and respiratuary parameters, Bispectral index score, Ramsey sedation score, time to achieve sufficient sedation, surgeon's and patients' satisfaction, postoperative Aldrete score and side effects were recorded. RESULTS: Time to achieve sufficient sedation, Bispectral index scores at 5, 10 and 15th. minutes intraoperatively, first Aldrete score in the recovery room, SpO2 values and respiratory rates all over the surgical procedure and in the recovery room were found lower in Group P (P<0.05). Bispectral index scores, mean arterial pressure and heart rate in the recovery room were significantly lower in Group D (P<0.05). CONCLUSION: Dexmedetomidine may be preferred as a safer agent with respecting to respiratory function compared with propofol in obstructive sleep apnea patients who known to be susceptible to hypoxia and hypercarbia. PMID- 26131154 TI - Association between vitamin D deficiency and insufficiency and the risk of childhood asthma: evidence from a meta-analysis. AB - OBJECTIVE: Whether vitamin D deficiency and insufficiency are associated with childhood asthma remains unclear. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of vitamin D deficiency and insufficiency and the risk of childhood asthma. METHODS: Pertinent studies were identified by searching of PubMed and Web of Knowledge. The random effect model was used to combine the results. Meta-regression and subgroups analyses were used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: Finally, 14 articles with 15 studies including 3424 cases for vitamin D deficiency and 9 articles with 10 studies including 2756 cases for vitamin D insufficiency were included in this meta-analysis. The relative risk (95% confidence interval) of childhood asthma risk for vitamin D deficiency was 1.684 (1.321-2.148), and the associations were significant in America and Europe. Significant association of childhood asthma between vitamin D insufficiency and childhood asthma risk was found overall [1.577 (1.230-2.023)] and the subgroups of America, Europe and Asia. No evidence of significant publication bias between vitamin D deficiency and insufficiency and childhood asthma risk were found. CONCLUSIONS: Results from this meta analysis suggested that vitamin D deficiency and insufficiency might increase the risk of childhood asthma. PMID- 26131155 TI - Relationship between epicardial adipose tissue thickness and vitamin D in patients with metabolic syndrome. AB - INTRODUCTION: Metabolic syndrome is a systemic disorder and manifests as a group of conditions including abdominal obesity, dyslipidemia, hypertension and coronary artery disease. The importance of epicardial adipose tissue has been proven through recognition of its contribution to inflammation by pro inflammatory cytokine discharge. Several investigations have been performed on vitamin D receptors in different tissues. In this study, epicardial adipose tissue thickness (EATT) and the levels of vitamin D were measured and compared with a healthy control group. MATERIAL AND METHODS: 84 patients who had metabolic syndrome without diabetes and 64 healthy individuals were enrolled into the study. In all patients, the EATT was calculated by ecocardiography and the level of serum 25 (OH) vitamin D was measured. RESULTS: It was observed that EATT in patients with metabolic syndrome increases significiantly compared to the healthy control group (P < 0.001). No significant difference between patients and control group was found for the levels of 25 (OH) vitamin D (P = 0.507). There was no correlation between 25 (OH) vitamin D and EATT (P = 0.622). CONCLUSIONS: We observed that EATT increased in patients with metabolic syndrome. In contradiction to literature; the levels of 25 (OH) vitamin D was not found to be high in patients with metabolic syndrome. Any significant correlation was not found between EATT and 25 (OH) vitamin D levels. Further studies with a larger patient population are required to assess the relationship. PMID- 26131156 TI - Ulnar impaction syndrome with different operative methods: a comparative biomechanical study. AB - OBJECTIVE: Ulnar impaction syndrome seriously impairs wrist and hand function. Three main treatment procedures are available; however, little systematic research on the post-operation changes in wrist biomechanics currently exists. This study aimed to determine the long-term effects of these procedures and the optimal treatment methods for ulnar impaction syndrome. METHODS: Twenty-four cases of fresh upper limb specimens were randomized into four groups: (1) the control group, (2) the ulnar-shortening operation group, (3) the Sauve-Kapandji procedure group (distal radioulnar arthrodesis and intentional distal ulnar pseudoarthrosis), and (4) the Darrach procedure group (distal ulna resection). After keeping the wrist in a neutral position, a pressure sensitive film was applied. Starting at 0 N, the load was increased gradually at a speed of 0.1 N/s until reaching 200 N and then maintained for 60 s by the CSS-44020 series biomechanical machine. Then, the pressure sensitive films from each group were measured, and the results were analyzed with SPSS software. RESULTS: The mean pressure and force on the ulna in the groups followed a decreasing trend from the control group, Sauve-Kapandji procedure group and ulnar-shortening operation group. The mean pressure of the scaphoid fossa and the force on distal aspect of the radius in the groups followed an increasing trend from the control group, Sauve-Kapandji procedure group, ulnar-shortening operation group and Darrach procedure group. This study found no significant differences in the mean pressure of the scaphoid fossa and the force on distal aspect of the radius between the Sauve-Kapandji procedure group and the ulnar-shortening operation group. The Sauve-Kapandji procedure group showed the greatest mean pressure on lunate fossa. CONCLUSIONS: In this comprehensive analysis of wrist biomechanics, the ulnar shortening operation was superior to the Sauve-Kapandji procedure and Darrach procedure, which adequately maintained the anatomical relationships of the wrist. PMID- 26131157 TI - Enhanced sedative efficacy and delayed recovery in propofol anesthesia in a rat model of hepatic cirrhosis. AB - PURPOSE: The sedative efficacy of propofol anesthesia is enhanced in patients with hepatic cirrhosis. Establish a rat model to investigate the efficacy of propofol. METHODS: 100 healthy Sprague-Dawley rats were divided into three groups and administered Phenobarbital sodium, carbon tetrachloride and ethanol solution for 0 (control), 9 (mild cirrhosis, M1), or 12 (severe cirrhosis, M2) weeks to induce hepatic cirrhosis. Propofol was infused via the caudal vein and the ED50 of the sedative effect and the recovery time were assessed according to the loss and recovery of the righting reflex. The effect of propofol on circulating cells and platelets, blood biochemistry and neurotransmitter content of the brain were measured. RESULTS: Cirrhosis was achieved in 25 of 35 M1 and 27 of 45 M2 rats. The propofol ED50 was significantly lower in M1 and M2 (5.8 +/- 1.2 and 4.8 +/- 1.1 mg/kg, respectively) than in control rats (6.2 +/- 1.1 mg/kg, P < 0.05), and the time to recovery of righting reflex was significantly longer in M1 and M2 (370.0 +/- 108.2 s and 501.6 +/- 100.1 s, respectively) than in control rats (275.0 +/- 90.3 s, P < 0.05). In M1 and M2 rats white and red blood cell and platelet counts were reduced, but ALT and AST activity was increased. In M1 and M2 rats the cerebral content of Gly and GABA increased but Glu and Asp were reduced. CONCLUSION: The sedative efficacy of propofol anesthesia is enhanced in rats with hepatic cirrhosis, perhaps due to reduced hepatic functional reserve, enhancement of inhibitory neurotransmitters and reduction of excitatory neurotransmitters. PMID- 26131158 TI - Selection of proximal fusion level for degenerative scoliosis and the entailing proximal-related late complications. AB - OBJECTIVE: To determine the optimal selection of proximal fusion level for degenerative scoliosis (DS) and investigate the long-term proximal-related complications. METHODS: Profiles of 95 consecutive patients with DS who underwent posterior long instrumented fusion were analyzed retrospectively. Perioperative parameters were reviewed stratified into 3 groups according to the relationship between the upper instrumented vertebrae (UIV), horizontal vertebrae (HV) and upper end vertebrae (UEV), namely HV Group (UIV = HV or above), HV-UEV Group (UIV = between HV and UEV) and UEV Group (UIV = UEV or below) in coronal plane and 3 groups in sagittal plane according to segment levels. Clinical and radiographic parameters were studied statistically. RESULTS: Average follow-up was 7.8 years (range, 5-13 years). HV Group showed a significant increase in operative time, intraoperative blood loss, postoperative in-bed time, and hospital stays. UEV Group showed greater average Cobb angle, AVT and DW. UEV Group showed significant increase in operative time, blood loss, postoperative in-bed time, and inpatient stay. All three groups showed significant improvement in ODI compared to baseline, while there was no significant difference in LL between three groups. Proximal-related late complications included recurrent junctional scoliosis in 4 cases and junctional kyphosis in 4 cases. CONCLUSIONS: Recurrent junctional scoliosis developed more commonly when the fusion was at or below the UEV, and fusion at L1 or L2 showed the highest incidence of junctional kyphosis. Long instrumented fusion to T11 or T12 appeared to be a reasonable alternative when the UIV was above UEV in DS. PMID- 26131159 TI - Hyperbaric spinal anesthesia with ropivacaine coadministered with sufentanil for cesarean delivery: a dose-response study. AB - Adjuvant sufentanil could achieve effective spinal anesthesia with low dose of hyperbaric ropivacaine for cesarean delivery. Two previous studies had calculated the 50% effective dose (ED50) of intrathecal ropivacaine coadministered with sufentanil for cesarean delivery. However, the 95% effective dose (ED95) of intrathecal hyperbaric ropivacaine coadministered with sufentanil for cesarean delivery remains uncertain. This study determined the ED95 of intrathecal hyperbaric ropivacaine coadministered with sufentanil for cesarean delivery. 80 ASA physical status I or II parturients undergoing elective cesarean delivery were enrolled in this prospective, randomized, double-blind investigation. A combined spinal and epidural anesthesia was performed at the L3-L4 interspace. Patients received a dose of spinal ropivacaine coadministered with sufentanil 5 MUg diluted to 3.0 ml with normal saline and 0.5 ml of 10% dextrose: 7.5 mg (n = 20), 9.0 mg (n = 20), 10.5 mg (n = 20), or 12 mg (n = 20). An effective dose was defined as a dose that provided bilateral sensory block to T7 within 10 min after intrathecal drug administration and required no epidural top-up for surgery to be completed. The ED50 and ED95 values for successful anesthesia were determined using a logistic regression model. The ED50 (95% confidence interval [CI]) for successful anesthesia was 8.4 (4.0-9.8) mg and the ED95 (95% CI) was 11.4 (9.7 13.9) mg. The results show that the ED95 of intrathecal hyperbaric ropivacaine coadministered with sufentanil 5 MUg for cesarean delivery was 11.4 mg. The addition of sufentanil could significantly reduce the dosage of ropivacaine. PMID- 26131160 TI - Role of ultrasound and microbubble-mediated heat shock protein 72 siRNA on ischemia-reperfusion liver injury in rat. AB - OBJECTIVE: To explore the ultrasound-guided gene transfection as well as the role of heat shock protein 72 (HSP72) siRNA combined with ultrasound micro-bubble contrast agents on rat hepatic ischemia-reperfusion injury. METHODS: 72 SD rats were divided into non-surgery group (group N), sham-operation group (group P) and liver ischemia-reperfusion groups (I/R). In each group, rats were further divided into 4 subgroups according to the different intravenous treatment: 220 ul saline solution (group A); 20 ul HSP72 siRNA plasmid vector + 200 ul saline solution (group B); 20 ul HSP72 siRNA plasmid vector + 200 ul ultrasound microbubble contrast agent (group C); 20 ul HSP72 siRNA plasmid vector + 200 ul ultrasound microbubble contrast agent + ultrasonic irradiation target region with MI1.0 (group D). RESULTS: Certain degree hepatic tissue injury was observed in rats of group I/R A, B and C. The expressions of liver tissue HSP72 mRNA and HSP72 protein and the concentrations of peripheral blood HSP72, ALT and TNF-alpha were significantly increased at each I/R subgroup (vs group N and group P, P < 0.01). Among them, the plasma concentrations of ALT, HSP72, and TNF-alpha and the liver tissue expressions of HSP72 mRNA and HSP72 protein at group A were significantly higher than groups B, C and D (P < 0.01). And group D was significantly lower than that of group A, B and C (P < 0.01). CONCLUSION: The liver tissue expressions of HSP72 mRNA and HSP72 protein and the liver injury degree of ischemia-perfusion were significantly reduced after the HSP72 siRNA was combined with micro-bubble and radiated directionally by ultrasound. PMID- 26131161 TI - Clinical research for delayed hemorrhage after endoscopic sphincterotomy. AB - To analyze the effect of delayed hemorrhage after endoscopic sphincterotomy (EST) and compare the efficacy in improving complication between medicine treatment alone and medicine combined with endoscopic treatment. 1741 patients with EST admitted in Yijishan hospital of Wannan medical college from September 2009 to May 2014 were enrolled in this study. 32 cases suffered from delayed hemorrhage. The patients with delayed hemorrhage were evaluated through incision length of duodenal papilla, clinical manifestation, stool occult blood test and the difference of hemoglobin concentration between pre and post operation. 32 patients were divided into mild bleeding group, mild serious group and serious group through the speed and amount of bleeding. All cases in mild group accepted medicine treatment. Mild serious group were divided into medicine therapy group and medicine combined with endoscopic therapy group randomly. Serious group accepted vascular intervention therapy even traditional operation. The different treatments for delayed hemorrhage were judged by efficiency. The dates were analyzed by t-test or chi-square test. Nobody endured delayed hemorrhage who accepted small incision. Delayed hemorrhage was found in 7 patients out of 627 cases who accepted medium-large incision, 25 patients of 920 cases who accepted large incision. The patients who accepted lager EST were more dangerous than small EST (chi(2)=4.718, P=0.030) concerning delayed hemorrhage. 32 cases in 1741 patients suffered from delayed hemorrhage. 14 patients only have passed black stool after EST. Among 14 cases, 13 patients stop bleeding after medical therapy, and 1 case received endoscopic hemostasis. 15 cases with hematemesis or melena after EST, 7 patients who received combination therapy stop bleeding. 3 patients from 8 cases stop bleeding after single chemical treatment, 5 cases had to receive endoscopic hemostasis after ineffectual medical therapy. There are significant difference for concerning effect between combination therapy group and medical therapy group (P=0.026). 3 patients repeatedly vomited blood and develop to peripheral circulatory failure. Those patients all received vascular intervention therapy, 2 patients stop bleeding, 1 patient failed in vascular intervention therapy and given up emergency rescue and died. Large EST has more risks than small EST in concerning delayed hemorrhage. Delayed bleeding after EST should be treated by different levels. Adapted therapy should be recommend for patients with different levels bleeding. PMID- 26131162 TI - Intraoperative sentinel lymph node mapping guides laparoscopic-assisted distal gastrectomy for distal gastric cancer. AB - AIMS: The aim of this retrospective study is to explore the effects of sentinel lymph node (SLN) mapping guided laparoscopic-assisted distal gastrectomy (LADG) for distal gastric cancer. METHODS: Two hundred patients were enrolled in this study. One hundred and one patients undergoing SLN guided LADG were designated as the SLN group. Ninety-nine patients having conventional LADG with D1 or D2 lymph node dissection were designated as the control group. Intraoperative and postoperative indicators such as the number of lymph nodes dissected, intraoperative and postoperative conditions, flow cytometry analysis of T lymphocyte subsets and natural killer (NK) cells, survival rates, recurrence rates and postoperative complications were investigated between these two groups. RESULTS: The number of lymph nodes dissected in the SLN group was significantly lesser than that in the control group. Furthermore, in the SLN group, the patients achieved better immunization status, improved intraoperative and postoperative conditions and decreased postoperative complications. There were no significant differences were found in the positive lymph nodes detected, the distance between proximal and distal cutting edge, postoperative survival or recurrence rates. CONCLUSIONS: SLN guided LADG for gastric cancer is a safe and effective method and could achieve an equal clinical effect as traditional laparoscopic D1 or D2 radical operation with less operation trauma and better recovery. PMID- 26131163 TI - Myocardial apoptosis and injury of donor hearts kept in completely beating status with normothermic blood perfusion for transplants. AB - OBJECTIVE: Normothermic blood perfusion is the developing trend of donor heart preservation. Theoretically, donor hearts preserved in a beating status may be the perfect method to reduce time-dependent ischemic injury, resuscitate marginal hearts expanding the donor pool and potentially improve the function of isolated hearts. In this study, to investigate the protective effect of normothermic blood perfusion, we maintained the donor hearts in a beating status and compared the changes of myocardial apoptosis and injury with standard hypothermic and static storage. METHODS: Thirty rat hearts were preserved in static cold storage (Group A, n=10, stored in 4 degrees C histidine-tryptophan-ketoglutarate solution), or in static normothermic blood perfusion (Group B, n=10, perfused with normothermic blood) or in beating status (Group C, n=10, perfused continuously with normothermic blood) for 9 hours. Myocardial injury markers including creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI), myocardial metabolic rate related indicators including Methane Dicarboxylic Aldehyde (MDA) and Adenosine Triphosphate (ATP) were investigated before and after preservation. And also TUNEL staining and mRNA and protein expression of apoptosis markers such as Bax, Bcl-2, Caspase-3 and Cleaved Caspase-3 were used to evaluated the degree of myocardial apoptosis. RESULTS: It is found that the levels of CK-MB and cTnI in Group C were significantly lower than those of Group A and Group B (P<0.05). However, there was no significant statistical difference of ATP content among three groups. When compared with Group A and B, the quality of MDA in Group C was obviously lower. In addition, it showed that a remarkable reduction in TUNEL positive nuclear staining in Group C but higher in other two groups. And inhibited apoptosis was also confirmed by the results of mRNA and protein expression of apoptosis markers including Bax and Bcl-2. CONCLUSIONS: It is an effective and appropriate approach to preserve donor hearts with continuous and normothermic blood perfusion as to keep them in beating status in heart transplantation, which could reduce myocardial ischemic damage and cardiac apoptosis in long-term preservation. PMID- 26131164 TI - Mastoid antral ventilation tube; new treatment modality for reccurent otitis media with effusion and its long term results. AB - OBJECTIVES: To evaluate the efficiency of mastoid antral ventilation tube (MAVT) treatment in recurrent/chronic otitis media with effusion (OME). METHODS: 20 OME patients who were unsuccessfully treated with ventilation tube (VT) at least twice, who consented to MAVT and who were followed up at least three years were included in the study group. Control group comprised 10 patients who had the same characteristics and refused to undergo MAVT and underwent VT placement again. Pre operative and post-operative otomicroscopic, hearing tests, and CT findings were compared between the groups statistically. RESULTS: MAVT was placed into 24 ears of 20 patients. In the control group, VT was placed in 13 ears of 10 patients. Postoperatively, in the study group, one tympanic membrane with adhesion and nine membranes with retraction returned to their anatomic positions after MAVT. In the control group, 2 retracted tympanic membranes returned to normal position. There was significant difference between groups in terms of mastoid aeration (P = 0.006). Post-operative pure tone threshold values and mastoid aeration findings were statistically different from preoperative conditions. CONCLUSION: This preliminary study demonstrates that MAVT may be effective in the surgical treatment of recurrent/chronic OME. However, further studies with larger patient series should be carried out. PMID- 26131165 TI - Transcutaneous electric acupoint stimulation alleviates remifentanil-induced hyperalgesia in patients undergoing thyroidectomy: a randomized controlled trial. AB - BACKGROUND: In this prospective, randomized, double-blind study, we verified the hypothesis that TEAS can alleviate remifentanil-induced hyperalgesia in patients undergoing thyroidectomy. METHODS: 60 American Society of Anesthesiologists physical status (ASA) I-IIpatients, aged 18-60 year, scheduled for thyroidectomy were randomly allocated to TEAS or sham groups. TEAS consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4) and Neiguan (PC6) before anesthesia. Anesthesia was maintained with sevoflurane adjusted to bispectral index (40-60) and target remifentanil 5.0 ng/ml. Mechanical pain thresholds were assessed using electronic von Frey. The primary outcome was mechanical pain thresholds. Secondary outcomes included postoperative pain scores, the time to first rescue analgesic, cumulative number of rescue analgesia, and side effects, including postoperative nausea and vomiting (PONV), dizziness and shivering in 24 h postoperatively. RESULTS: Baseline mechanical pain thresholds were similar between the groups. The analysis revealed the decrease in mechanical threshold was greater in the sham group than the TEAS group (P < 0.001). Postoperative pain scores and cumulative number of rescue analgesia were lower in the TEAS group (P < 0.05). In addition, TEAS group patients reduced the incidence of PONV and shivering. CONCLUSION: Preoperative TEAS can attenuate remifentanil-induced hyperalgesia in patients undergoing thyroidectomy. PMID- 26131166 TI - Angiotensin-converting enzyme insertion/deletion polymorphism and gastric cancer: a systematic review and meta-analysis. AB - Previous case-control studies on the association of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with gastric cancer were controversial. A meta-analysis was conducted to further evaluate the association between polymorphism in the ACE gene I/D and gastric cancer. We searched MEDLINE (PubMed), EMBASE, Web of Science, and CBM without language restrictions to Nov 20, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Eight studies involving 1480 gastric cancer cases and 3773 cancer-free controls were included. Overall, no significant association between ACE I/D polymorphism and gastric cancer risk was observed (OR = 1.15; 95% CI 0.90-1.46, P = 0.26). The subgroup analysis on the basis of H. Pylori status showed the decreased gastric cancer risk in H. Pylori negative subgroup (OR = 0.40; 95% CI: 0.27-0.59; P < 0.00001) rather than in H. Pylori positive subgroup (OR = 1.82, 95% CI: 0.87-3.82, P = 0.11). Subgroup analysis was performed according to ethnicity (Caucasian and Asian). The results showed no genetic effects between ACE I/D polymorphism and gastric cancer risk. This meta analysis suggested that the ACE gene I/D polymorphism was associated gastric cancer risk in H. Pylori negative subjects. PMID- 26131167 TI - Antibacterial activity of silver nanoparticles target sara through srna-teg49, a key mediator of hfq, in staphylococcus aureus. AB - Attributed to its antimicrobial effect, Silver nanoparticles (AgNPs) is widely used in various fields, such as biomedicine, textiles, health care products and food, etc. However, the antibacterial mechanism of AgNPs in staphylococcus aureus (S. aureus) by regulating sRNA expression remains largely unknown. OBJECTIVES: This study was performed to investigate the involvement of the antibacterial mechanism of AgNPs through sRNA-TEG49, a key mediator of Hfq, in S. aureus. METHODS: Through the antimicrobial tests of AgNPs, its antibacterial laps and minimum inhibitory concentration was measured. A hierarchical cluster analysis of the differentially expressed sRNA in S. aureus was performed to investigate the relationship between AgNPs and sRNA. Expression of genes was analyzed by real time PCR. RESULTS: In the present study we found that at the concentrations higher than 1 mg/L, AgNPs could completely restrain bacteria growth, and the antibacterial activity of AgNPs apparently declined at the concentrations lower than 1 mg/L. S. aureus exposure to AgNPs, the expression of sRNA-TEG49, Hfq and sarA was significantly up-regulated in wild-type S. aureus. Moreover, Hfq loss-of function inhibited the expression of sRNA-TEG49 in mutant-type S. aureus. Furthermore, sRNA-TEG49 loss-of-function associated with down-regulation the expression of sarA in mutant-type S. aureus. CONCLUSIONS: It was reasonable that Hfq regulated a distinct underlying molecular and antibacterial mechanism of AgNPs by forming a positive feedback loop with sRNA-TEG49. These observations suggested that Hfq plays an important role in the antibacterial mechanism of AgNPs by regulating sRNA-TEG49 expression, via its target sarA. PMID- 26131168 TI - Diagnostic value of CT artifacts for solitary coarse calcifications in thyroid nodules. AB - This study aimed to estimate the diagnostic value of CT artifacts for solitary coarse calcifications (SCC) in thyroid nodules. A total of 78 SCCs (coarse calcifications >2 mm, no definite mass lesion around calcification) in 63 cases received surgery from Jan 2009 to Jun 2014 were enrolled, including 52 nodular goiters (NG) in 41 cases and 26 papillary thyroid carcinomas (PTC) in 22 cases. The CT artifacts in NGs and PTCs were recorded, and its sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, false negative rate and accuracy for the diagnosis of NG were calculated. CT artifacts were more often observed around the SCCs in NG cases (P<0.05), its sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, false negative rate and accuracy for the diagnosis of NG were 80.7%, 76.9%, 87.5%, 66.7%, 23.1%, 33.3% and 79.5%, and there was no intergroup difference about the CT artifacts in SCCs (P>0.05). CT artifacts are important for the diagnosis of SCCs in thyroid nodules to tell benign from malignancy, and CT artifacts around the SCC are helpful for the diagnosis of NG and no artifacts indicate a larger probability of PTC. PMID- 26131169 TI - Comparison of antibacterial effects between antimicrobial peptide and bacteriocins isolated from Lactobacillus plantarum on three common pathogenic bacteria. AB - New strategies for the prevention or treatment of infections are required. The purpose of this study is to evaluate the effects of antimicrobial peptides and bacteriocins isolated from Lactobacillus plantarum on growth and biofilm formation of three common pathogenic microbes. The antibacterial properties of the antimicrobial peptide Tet213 and bacteriocins were tested by the disc diffusion method. Tet213 and bacteriocins showed inhibitory effects on biofilm formation for the three organisms, as observed by fluorescence microscopy. Furthermore, Tet213 and the bacteriocins all showed antimicrobial activity against the three bacterial species, with Tet213 having a greater inhibitory effect on S. aureus than the bacteriocins (P < 0.05), while the bacteriocins showed stronger antimicrobial activity against S. sanguis (P < 0.05). PMID- 26131170 TI - Neutrophilic infiltration in lungs of mice with peritonitis in acid or basic medium. AB - BACKGROUND: Bacterial peritonitis is associated with systemic complications such as pneumonia. OBJECTIVE: To determine in an experimental model of peritonitis whether the pH of peritoneal fluid infection influences the influx of neutrophils into the lung, and whether treatment outcome would be similar in peritonitis with liquid at any pH. MATERIALS AND METHODS: We studied 48 mice with peritonitis induced by cecal ligation and puncture. The animals were distributed randomly into three groups: the first one had an injection into the peritoneal cavity with saline, pH 7.0; the second group was injected with saline, pH 8.0; and the third group with saline, pH 3.0. After 2 hours, half the animals in each group was treated by washing the abdominal cavity with warm saline solution and administration of ceftriaxone every 12 hours, and half of each group was killed by anesthetic overdose, and lung biopsy was done. The animals kept in treatment were killed 24 hours after treatment, and lung biopsy was also performed. The samples were stained with H&E and the number of neutrophils in 20 areas was checked. The mean number of cells in each group was compared between groups and with an untreated one. RESULTS: The group with peritonitis associated with alkaline solution showed a higher population of neutrophils during untreated peritonitis (P = 0.04). The response to treatment by lavage of the peritoneal cavity and antibiotics was more effective in reducing the population of neutrophils in the group with peritonitis at pH 8.0, unlike that observed in animals with peritonitis at pH 3.0 (P = 0.03). CONCLUSION: Peritonitis associated with lower pH solution, despite the lower influx of leukocytes in the first two hours after installation of peritonitis, was not able to reduce the population of these cells in mice's lung in response to standard therapy. PMID- 26131171 TI - Fertility-sparing treatment of low-grade endometrial stromal sarcoma. AB - Low-grade endometrial stromal sarcoma (ESS) is a kind of uterine malignancy. Total hysterectomy and bilateral salpingo-oophorectomy was the main treatment. We evaluate the feasibility of fertility-sparing management in five patients with low-grade ESS who desired for childbearing. The patients aged 28-36 years old presented with symptoms of menometrorrhagia or without symptom. Ultrasound examinations demonstrated leiomyomas (with the diameter of 3.5-6 cm respectively). All the patients received conservative surgeries of local resection of the mass with uterine reconstruction. Then the adjuvant endocrine therapy was given to them with megestrol acetate (160-320 mg/day) or triptorelin (3.75 mg/28 days) for 5-6 months. The follow-up lasted 21-55 months. All the patients survived. Three of them underwent an uncomplicated pregnancy, and received cesarean delivery of a liveborn neonate. One of them is alive without disease recurrence. The other one found disease recurred during the megestrol acetate treatment, and received hysterectomy. We consider that fertility-sparing treatment is suitable in selected in young low-grade ESS patients especially for those whose lesion was with a clear borderline. Adjuvant endocrine therapy is recommended for about 6 months after operation. PMID- 26131172 TI - MDM2 SNP309 variation confers the susceptibility to hepatocellular cancer: a meta analysis based on 4271 subjects. AB - Previous reports have indicated that MDM2 T309G polymorphism might be a risk factor for various cancers. Increasing studies have been conducted on the association of MDM2 T309G polymorphism with hepatocellular carcinoma (HCC) risk. However, the results remain inconclusive. Thus, the present study aimed to address this controversy by meta-analysis. Relevant literature up to Oct 2014 was searched and screened. Necessary information was rigorously extracted for data pooling and analyzing. Separate analyses on ethnicity, source of controls, sample size and P53 polymorphism status were also performed. As a result, eleven case control studies were selected and the overall data indicated a significant association of MDM2 T309G polymorphism with HCC risk (GG vs. TT: OR=2.31; 95% CI=1.66-3.20; dominant model: OR=1.83; 95% CI=1.36-2.47; recessive model: OR=1.73; 95% CI=1.49-2.00). Similar results could be shown in the subgroups regarding ethnicity, source of controls and sample size. Interestingly, in the subgroup analysis regarding P53 codon 72 polymorphism, increased HCC risk could be observed in the Pro/Pro+Pro/Arg subgroup under a recessive model (OR=1.78; 95% CI=1.29-2.44). In conclusion, the results of the present study suggest that MDM2 T309G polymorphism might be a low-penetrant risk factor for HCC. Homozygous GG alleles might interact with Pro of P53 and thus confer the susceptibility to HCC. PMID- 26131173 TI - A novel endovenous laser ablation strategy of treatment of greater saphenous vein varicosities with difficult wire placement. AB - AIM: To investigate the efficacy and early postoperative morbidity of a novel endovenous laser ablation (IEVLA) strategy of treatment of the great saphenous vein (GSV) with difficulty of wire placement. METHODS: Sixty patients with serious GSV incompetence in 73 limbs were randomized into two treatment groups: Group 1 underwent traditional endovenous laser ablation (TEVLA) surgery and group 2 received IEVLA. Local pain, ecchymosis, induration, paraesthesia in treated regions, thrombotic diseases, vein diameter, treated vein length, delivered energy, operation duration, success rate in placement of the laser fiber and venous clinical severity (VCS) scores were recorded for both group. Follow-up were conducted on the 2nd day, 7th day, and 1st, 2nd, 3rd and 6th month postoperatively. RESULTS: In group 1, induration was present in 18 cases, ecchymosis in 19, paraesthesia in 9, pulmonary embolism (PE) in 1 case, and deep vein thrombus (DVT) in 3. While in group 2, induration present in 29, ecchymosis in 23, paraesthesia in 17 with and no patients were complicated with PE or DVT. Although no difference in improvement of VCS score existed between the two groups at each follow-up time point, group 2 had significantly shorter operation time and higher success rate (P < 0.05). CONCLUSION: IEVLA is a more effective and safe technique for treatment of serious GSV varicosities with difficulty of wire placement. PMID- 26131174 TI - Perineural invasion: a potential reason of hepatocellular carcinoma bone metastasis. AB - The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. Perineural invasion (PNI) is the only interaction between cancer cells and nerves studied to date. It is a symbiotic relationship between cancer cells and nerves that result in growth advantage for both. The potential association between HCC bone metastases and PNI is unknown. In this study, we investigate the nerve density in HCC and paired bone metastases to reveal the potential association of HCC bone metastases and PNI. The nerve density was evaluated by immunohistochemistry in formalin-fixed paraffin embedded (FFPE) hepatocellular carcinoma (HCC) and paired bone metastases tissues from 13 HCC patients with synchronous or metachronous bone metastases that underwent surgical resection. FFPE specimens of HCC bone metastases tissues express higher perineural density than HCC tissues, pointing to a potential role of the PNI in bone metastases from HCC. This is the first description of the potential association of PNI and HCC bone metastases. PMID- 26131175 TI - Prognostic value of survivin in patients with non-Hodgkin's lymphoma: a meta analysis. AB - BACKGROUND AND OBJECTIVES: Numerous studies have focused on the role of survivin in non-Hodgkin's lymphomas (NHLs), but evidence regarding the prognostic value of survivin with respect to overall survival (OS) in NHL remains controversial. The aim of this study is to gain a better insight about the direct relationship between survivin expression and patients' survival statuses. MATERIALS AND METHODS: Relevant publications addressing the association between survivin expression and OS in NHL patients were selected from PubMed, Embase, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database and the Cochrane library. Studies were pooled and summary hazard ratios (HR) were calculated. Sensitivity analyses and publication bias were also conducted. Statistical analysis was performed by STATA 12.0 software. RESULTS: 12 studies met the inclusion criteria. Combined HRs suggested that survivin overexpression had an unfavorable impact on NHL patients' survival (HR=1.55, 95% CI=1.12-2.13, P=0.008). Subgroup analyses according to the studies categorized by histological type, ethnicity, cutoff scores and follow-up period were also conducted, and all the above analyses supported the stability of the prognostic role of survivin. CONCLUSION: Our findings suggest that survivin high expression might be a poor prognostic factor for patients with NHL. However, further large scale studies are needed to confirm these findings. PMID- 26131176 TI - CT-guided microinvasive intervention in treating refractory carcinous pain. AB - OBJECTIVE: To evaluate the analgesic effect of CT-guided microinvasive intervention on refractory carcinous pain. METHODS: A total of 23 patients with poor response to drug therapy for carcinous pain were selected: 6 patients underwent CT-guided neurolytic celiac plexus block (NCPB), 5 patients underwent CT-guided(125)I implantation and 12 patients underwent combined CT-guided NCPB and CT-guided(125)I implantation. RESULTS: After 1 week of treatment, 6 patients exhibited complete remission, 13 patients exhibited partial remission and 4 patients exhibited no changes in condition. The treatment efficiency rate was 82.6%. After 1 month of treatment, 5 patients exhibited complete remission, 14 patients exhibited partial remission and 4 patients exhibited no changes in condition. Treatment efficiency rate was 82.6%. After 3 months of treatment, 4 patients exhibited complete remission, 9 patients exhibited partial remission, 5 patients exhibited no changes in condition and 5 patients died. Treatment efficiency rate was 72.2%. After 6 months of treatment, 3 patients exhibited complete remission, 6 patients exhibited partial remission, 3 patients exhibited no changes in condition and 11 patients died. The treatment efficiency rate was 75.0%. No severe postoperative severe complications, such as bleeding, biliary fistula and pancreatic fistula, were reported. CONCLUSION: CT-guided microinvasive intervention clearly demonstrated an analgesic effect on refractory carcinous pain with less trauma and few complications. Therefore, this method provides effective relief for carcinous pain. PMID- 26131177 TI - Association between COL1A1 polymorphisms and high myopia: a meta-analysis. AB - BACKGROUND: Previous studies of the association between COL1A1 polymorphisms and high myopia risk have yielded conflicting results. To help resolve the discrepancies, we performed a meta-analysis to estimate the relationship between COL1A1 polymorphisms and high myopia risk. METHODS: We searched for case-control and cohort studies in MEDLINE, EMBASE, and OVID. Odds ratios (OR) with 95% confidence intervals (CI) were derived for single-nucleotide polymorphisms (SNPs). We also analyzed heterogeneity and publication bias. RESULTS: This meta analysis was based on five studies of rs2075555 (1,944 high myopia cases and 3,060 controls), and three studies of rs2269336 (1,454 high myopia cases and 1,512 controls). The combined results showed an association between rs2075555 and high myopia in the dominant (OR = 0.86, 95% CI = 0.71-0.99) and homozygote models (OR = 0.79, 95% CI = 0.64-0.97). In the recessive model for rs2269336, OR was 1.26 (95% CI = 1.05-1.50); in the heterozygote model, OR was 0.81 (95% CI = 0.69 0.96). Begg's and Egger's tests for rs2075555 showed no evidence of publication bias. CONCLUSIONS: This meta-analysis suggests COL1A1 rs2075555 is a potential low risk factor for high myopia. PMID- 26131178 TI - A retrospective comparative study of clinicopathological features between young and elderly women with breast cancer. AB - OBJECTIVE: This is a retrospective study to compare the clinicopathological features between young and elderly women with breast cancer. METHODS: Totally 181 young and 186 elderly breast cancer patients were analyzed and compared in respects of the histological subtype, tumor number and size, tumor location, histological grading, UICC-pTNM pathological staging, and lymph node metastasis status. RESULTS: Our results showed that invasive ductal carcinoma was the most frequent histotype in young and elderly breast cancer patients. The second most frequent histological subtype was intraductal carcinoma in the young group, while the second leading histotype was invasive lobular carcinoma in the elderly group. No significant differences in tumor number and location were observed between the young and elderly groups. The percentage of patients with tumor size T3 (diameter > 5 cm) and the proportion of patients with histological grade III in the young group were significantly higher than the elderly group. For UICC-pTNM pathological staging, patients at stages 0-I and II in the young group were less than, while patients at stage III was more than, in the elderly group. In addition, the axillary lymph node metastasis rate and the numbers of axillary lymph node metastasis were elevated in the young group, compared with the elderly group. CONCLUSION: Breast cancer in young female patients is associated with increased aggressiveness and potential malignancy. Our findings might contribute to future diagnosis and treatment of breast cancer in young women. PMID- 26131179 TI - The role of n-butyl-2-cyanoacrylate in the repair of traumatic diaphragmatic injuries. AB - Diaphragmatic injuries either by blunt or penetrating trauma require prompt surgical intervention and are often exigent to repair. N-butyl-2-cyanoacrylate (n butyl-2-CA) is a tissue adhesive which has gained wide application in many areas of surgery including emergency. To repair the extensive injuries of the diaphragm it may be necessary the use of synthetic mesh by fixing it with sutures or staples. The use of tissue adhesives may circumvent the potential problems associated with mesh fixation. This study aimed to evaluate the efficacy and safety of tissue adhesives usage for mesh fixation in diaphragmatic injury repair. Twenty-four rats were divided into 3 groups each of them containing 8 rats. A 1- cm diaphragmatic defect was created in all rats. The defect was repaired by polypropylene suture in Group I, by mesh fixed with sutures in group II and by mesh fixed with n-butyl-2-CA in group III. The rats were sacrificed after 1 month. The episode of hernia and the adhesions were assessed by adhesion density score. Also, the abscess and inflammation in the repaired tissue were evaluated microscopically. The Kruskal-Wallis test was performed for the histopathological analysis. No diaphragmatic hernia was detected in any group. While Group III had higher adhesion density scores than group I (P: 0.027), there were no differences between group III and II (P: 0.317) and group II and I (P = 0.095) regarding adhesion density scores. The inflammation grade was higher in group III than group I and II (P < 0.001) and was higher in group II than group I (P < 0.05). There was no differences between each groups, concerning microabcsess formation (P > 0.05). Repair of traumatic diaphragmatic injury in penetrating wound, with polypropylene mesh fixed by n-butyl-2-CA in rats appears to be as efficacious and safe as conventional methods in early period. However, further experimental and clinical study are needed to compare the long-term results of adhesive mesh repair with those of the traditional sutured techniques. PMID- 26131180 TI - Expression of CXCR2 and its clinical significance in human colorectal cancer. AB - In the present study, we detected CXC chemokine receptor-2 (CXCR2) CXCR2 expression in patients with colorectal cancer (CRC) and investigated the correlation of CXCR2 expression with clinicopathological variables. CXCR2 expression levels in 46 cancerous tissues, 20 colonic benign tumour tissues, and 30 normal colonic mucosa tissues were examined at both the mRNA level and protein level by using reverse transcription polymerase chain reaction (RT-PCR) and two step immunohistochemical staining, respectively. We found that the positive rate of CXCR2 protein expression in cancer tissue samples was 69.6%. RT-PCR results confirmed that CXCR2 expression was significantly higher in tumour tissues compared with benign tumour and normal mucosa tissues (P < 0.05). When 46 colorectal cancer patients were divided into groups according to the clinical stage, lymph node metastasis and liver metastasis, we found that CXCR2 expression increased in patients with lymph node metastasis (P < 0.05), and its expression was much higher in stage III and IV cancers than stage I and II cancers. These findings suggest that CXCR2 expression in CRC patients may be a potential molecular biomarker for evaluation of tumour growth and invasion. PMID- 26131181 TI - The impact of sub-clinical over-hydration on left ventricular mass in peritoneal dialysis patients. AB - OBJECTIVE: Left ventricular hypertrophy (LVH) represents a major predictor of the development of cardiovascular (CV) complications. Over-hydration (OH) is an important uremic risk factor associated with LVH and increased CV morbidity and mortality in peritoneal dialysis (PD) patients. In the present study we evaluated the prevalence of sub-clinical OH (SCOH) among PD patients and its effects on left ventricular mass (LVM). METHODS: In this cross sectional study hydration status, blood pressure, glucose load, systemic inflammation and LVM were evaluated in 43 clinically stable patients on maintenance PD for 24-76 months. The hydration status was assessed by whole-body bio-impedance spectroscopy (BIS). Peripheral edema and any evidence of pulmonary congestion were considered clinical signs of OH. RESULTS: OH >= 1.5 L was detected in 26 (60.5%) of the study participants; the OH in 19 (73.1%) of them was sub-clinical. Only 23.5% (4/17) of patients with OH < 1.5 L had LVH compared to 68.4% (13/19) of those with SCOH >= 1.5 L (P = 0.007). Compared to patients with OH < 1.5 L, patients with SCOH >= 1.5 L had higher levels of blood pressure, peritoneal glucose load, plasma brain natriuretic peptide, high sensitive C-reactive protein, interleukin 6 and LVMI; and lower levels of serum albumin (P < 0.001). No significant differences were found between patients with clinical OH or SCOH with OH >= 1.5 L. CONCLUSIONS: SCOH is highly prevalent among PD patients and may contribute to the development of LVH. Considering the poor prognosis associated with over hydrated PD patients, periodic assessment of hydration status using accurate BIS is suggested. PMID- 26131183 TI - The relationship between histopathological and imaging features of sacroiliitis. AB - This study aimed to investigate the histopathological feature of sacroiliitis and to examine its relationship with imaging features using various imaging techniques. Computed-tomography (CT)-guided needle biopsy of the sacroiliac (SI) joints was performed in 36 patients with spondyloarthritis. Histopathological examination was performed on the samples and subjects were divided as with or without sacroiliitis according histopathology. Magnetic resonance imaging (MRI), Single-photon emission CT (SPECT), CT scans and plain X-rays of the SI joints were conducted. Histopathological changes indicative of sacroiliitis were found in 29 (81%) of the 36 patients, with changes in cartilage (72.4%) and subchondral bone (72.4%) being the most common features. Histopathological sacroiliitis was not found in seven (19.4%) patients. Using MRI, sacroiliitis was found in 29 (80.5%) patients. Increased SI index (> 1.34) by SPECT scans indicative of sacroiliitis was found in 29 (80.5%) patients. Sacroiliitis was detected by CT and plain X-rays in 23 (63.8%) and 19 (52.7%) patients, respectively. Using the histopathological sacroiliitis as the gold standard, sensitivity for SPECT, MRI, CT and plain X-rays was 92.8%, 96.4%, 73.3%, respectively, and 64.2% and the corresponding specificity was 62.5%, 75%, 87.5% and 87.5%, respectively. Needle biopsy is an important method for the diagnosis of sacroiliitis. MRI and SPECT have comparable diagnostic value as CT and plain X-rays and can quantify the inflammatory activity. A combination of these two techniques could increase the sensitivity and specificity and serve as a valuable tool for the diagnosis, assessment and monitoring of sacroiliitis. PMID- 26131182 TI - GSK3beta expression and phosphorylation during neuronal maturation in the rat dorsal root ganglion. AB - Glycogen synthase kinase 3beta (GSK-3beta) protein is a key regulator of neurogenesis, neuronal differentiation and polarisation during neurodevelopment. Sensory neurons in dorsal root ganglion (DRG) undergo a series of development stages during its maturation. In this study, we investigated the dynamic changes in GSK-3beta expression and phosphorylation of its N-terminal serine-9 residue (p GSK-3beta (S9)) during DRG development. Sprague-Dawley (SD) rats were divided according to the following ages: Embryonic 13(th) (E13), E15, E19, Postnatal 1(st) (P1), P3, P7, P14, P21 and P60 days. GSK-3beta was detected by immunohistochemistry and double immunofluorescence on DRGs. Western blotting was used to determine the quantity of GSK-3beta and p-GSK-3beta (S9) expression. It was found that GSK-3beta immunopositive cells in the DRG appeared as early as E13 development phase, and gradually increased to a peak level at P3, at which almost all neurons were GSK-3beta positive, and then stayed at a high level to the experiment day 60. GSK3beta expression was cell-type-specific during DRG maturation and exhibited cytoplasmic staining in the neuronal cell body and the axon. Glial cells consistently remained negative in DRGs at all stages. Western blot analysis revealed that GSK3beta expression stayed the same during DRG maturation. In contrast, p-GSK-3beta (S9) expression was stage-specific and decreased from E13 to P60 (P < 0.01). Taken together, these results suggest that GSK-3beta expression is stage-specific and cell-type-specific during DRG maturation. PMID- 26131184 TI - Prospective validation of an ultrasound-based thyroid imaging reporting and data system (TI-RADS) on 3980 thyroid nodules. AB - OBJECTIVE: Ultrasound (US) features of solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape are suspicious characteristics for thyroid nodules. An US based Thyroid Imaging Reporting and Data System (TI-RADS) is classified based on the number of aforesaid features. TI-RADS category 3 included nodules without any suspicious features, and categories 4a, 4b, 4c, and 5 included nodules with one, two, three or four, or five suspicious US features. The purpose of the study was to prospectively validate the effectiveness of the TI-RADS. METHODS: From October 2011 to June 2013, we prospectively categorized 3980 thyroid nodules (3752 benign and 228 malignant lesions) in 2921 patients using TI-RADS classification. TI-RADS categories 2 and 3 were considered as benign whereas TI-RADS categories 4 and 5 as malignant. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy were calculated. RESULTS: Of the 3980 nodules, 2953 nodules were TI-RADS category 2 (0% malignancy), 466 nodules TI-RADS category 3 (1.3% malignancy), 186 nodules TI-RADS category 4a (4.8% malignancy), 165 nodules TI-RADS category 4b (30.3% malignancy), 188 nodules TI RADS category 4c (75.5% malignancy), and 22 nodules TI-RADS category 5 (95.5% malignancy). The sensitivity, specificity, PPV, NPV and accuracy were 97%, 90%, 40%, 99%, and 91%, respectively. CONCLUSIONS: TI-RADS classification had great diagnostic value in diagnosing thyroid nodules. The actual probability of malignancy was in accord with the theory risk of malignancy. PMID- 26131185 TI - Magnetic resonance imaging investigations of position of conus medullaris in adolescent idiopathic scoliosis as a peripheral neuropathy. AB - Adolescent idiopathic scoliosis (AIS) is a structural 3-dimensional deformity the spine, which is occurring between 10 years of age and skeletal maturity and it mostly affects prepuberbal girls. The etiology of AIS remains unknown and seems should be multifactorial. According to the theories, there could be a shorter spinal cord or a higher location of the conus medullaris and disproportionate growth in neuro-osseous system. This study wants to investigate the position of the conus medullaris in AIS patients with a large curve magnitude in comparison with healthy adolescents. 94 AIS patients consisting of 25 males and 69 females between 11 and 25 years old, based on physical examination and standing posteroanterior roentgenography of the total spine with a Cobb angle more than 40 degrees was chosen. The main curve magnitude of every AIS patient was measured by the Cobb method. Apex of deformity was determined based on SRS definition. Patients' deformity were calcified based on Lenke classification. Magnetic resonance imaging examinations of the total spine were performed in the AIS group, by means of a 1.5-T magnetic resonance imaging system. The position of conus medullaris was defined according to the method by saffiudin et al and was assessed based on the age, sex, type of deformity, severity of deformity, kyphosis, lordosis, flexibility, apical vertebra, stable vertebra. The mean age of patients were 16.34 with 6.77 of conus medullaris position in mean, which was lower one-third of L1. Our study showed no significant correlation between the position of conus medullaris with age, weight, preoperative curve, flexibility, types of deformity based on Lenke classification and degree of kyphosis and lordisis. In conclusion, there is the same mean and the distribution of the conus medullaris locations for AIS patients and normal populations. PMID- 26131186 TI - Analysis of fungal ball rhinosinusitis by culturing fungal clumps under endoscopic surgery. AB - OBJECTIVE: This study was designed to investigate the clinical microbiology of fungal ball (FB) rhinosinusitis by culturing fungal clumps collected under endoscopic surgery. METHODS: From April to November of 2012, fungal clumps were sampled by endoscopic surgery from patients diagnosed with FB using clinical and histopathological methods. The specimens were subjected to smear microscopy, and cultured for bacteria and fungi analysis. RESULTS: Out of the 81 specimens from 80 patients, 69 (69/81, 85.19%) specimens were detected a mixed infection of bacteria and fungi. However, only 25 (25/81, 30.86%) specimens resulted in fungal growth. There were 12 (12/81, 14.81%) specimens with fungal infections alone. The cultured fungi included 36 strains belonging to five genera, and most of them were Aspergillus spp. (30/36, 83.3%). The cultured bacteria included 94 strains belonging to 16 genera, and the most frequently seen was Staphylococcus spp. (23/94, 35.94%). When it was fungal and Pseudomonas aeruginosa mixed infection, the fungal growth was inhibited (P = 0.002). CONCLUSION: Patients with fungal ball usually have mixed fungal and bacterial infections. The fungi from these samples are sometimes difficult to culture, which may be the result of the inhibition by bacteria in vitro and in vivo. PMID- 26131187 TI - Polyethylene-oxide improves microcirculatory blood flow in a murine hemorrhagic shock model. AB - BACKGROUND: Polyethylene oxide (PEO) is a synthetic polymer commonly used in medicine production to reduce toxicity. In the present study, we assessed whether PEO can have a functional effect on improving microcirculatory blood flow after hemorrhagic shock in an animal model. METHODS: Hemorrhagic shock (HS) was introduced in 78 C57BL/6 mice, which were then equally divided into two groups. One group of mice was intravenously injected with PEO (diluted in Ringer's solution (RS), PH = 7.4), and the other with RS only. The parameters of microcirculatory hemodynamics, arterial blood gas analysis and multi-organ functions were compared between two groups, 0, 3, 12 and 24 hours after resuscitation. RESULTS: After HS, the hemodynamics, including microvascular diameter, red blood cell velocity, and blood flow rates were significantly improved in time-dependent manners in PEO treated mice. Most parameters of arterial blood gas analysis, except PCO2, were also significantly improved by PEO. Multi-organ immunohistochemistry demonstrated that congestions and inflammatory responses in liver and lung were markedly ameliorated by PEO. CONCLUSIONS: Our results demonstrated that PEO infusion could effectively improve microcirculation after hemorrhagic shock and increase the chance of survival in animal models. PMID- 26131188 TI - Prognostic impact of platelet/lymphocyte and neutrophil/lymphocyte ratios in patients with gastric cancer: a multicenter study. AB - BACKGROUND: Increasing amounts of evidence suggest patient-related systemic inflammatory response (SIR) as a powerful prognostic factor in cancer and applicability of SIR as a prognostic factor has been investigated. AIM: To evaluate the prognostic significance of SIR, which is among routinely analysed blood parameters in patients with all stages of gastric cancer (GC). METHODS: A total of 245 patients with gastric cancer who were followed up and treated in four clinics of medical oncology were included in the study. At first admission of the patients, from routinely determined whole blood cell counts in medical oncology clinics, their neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) values were estimated and recorded before initiating chemo- or radiotherapy. A univariate non-parametric analytical method and chi-square test examined the correlation between prognostic factors, and survival rates. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Sixty-eight (27.8%) female and 177 (72.2) male patients (total n=245) were included in the study. When NLR was used as an indicator of SIR, 108 (44.1%) patients were SIR negative and 137 (55.9%) patients were SIR positive. When PLR was used as an indicator of SIR, SIR negativity and positivity were detected in 93(38%) and 152 (62%) patients, respectively. A statistically significant correlation was found between status of lymph node metastasis, stage of the disease and NLR (P=0.001, P=0.017). SIR determined with PLR was found to be correlated with the depth of tumor invasion and stage of the disease (P=0.016, P=0.033). A significant correlation was not detected between PLR and survival (P=0.405). CONCLUSION: According to our study, parameters of NLR and PLR calculated preoperatively from peripheral blood samples can be used in patients with various sizes of tumours in different disease stages. Still based on our results, NLR calculated during diagnostic workup is a parameter with a prognostic value. In addition, NLR is a determinative factor in the selection of surgical method and chemotherapeutic modalities, which also functions as a potential contributory marker in effective immunotherapeutic strategies. PMID- 26131189 TI - Joint cavity injection combined with manual reduction and stabilization splint treatment of anterior disc displacement. AB - AIM: This study aimed to compare the clinical efficacy of upper and lower joint cavity treatment (UJCT vs. LJCT) in patients with anterior disc displacement without reduction (ADDw/oR) of temporomandibular joint (TMJ). MATERIAL AND METHODS: A total of 56 patients with unilateral ADDw/oR were randomly divided into two groups: UJCT group and LJCT group. Manual reduction was done in all the patients after joint cavity rejection of sodium hyaluronate. Then, they were treated with stabilization splint for one or two months. At last, Friction index was calculated to evaluate the therapeutic efficacy at 6 to 12 months follow-up. RESULTS: The maximal mouth-opening degrees in the both groups increased significantly when compared with pre-treatment group (P < 0.01), and the Friction index decreased significantly when compared with pre-treatment group (P < 0.01); In LJCT group, the degrees of maximal mouth-opening increased significantly as compared to UJCT group (P < 0.05), and Friction index were also markedly lower than that in UJCT group (P < 0.05). CONCLUSION: In the patients with ADDw/oR of TMJ, the clinical efficacy of LJCT is superior to that of UJCT, especially in the TMJ pain relief, mouth-opening degree and mandibular movement improvement. PMID- 26131190 TI - Osteoporosis biomarkers act as predictors for diagnosis of chronic renal insufficiency in elder patients. AB - Chronic renal insufficiency and osteoporosis have become very common among old people in China. Hyperparathyroidism caused by renal insufficiency would result in turbulence of bone metabolism and unbalance between serum calcium and phosphorus. The aim of this study is to investigate the BMD, PTH, CT and 25(OH) Vit's significance for screening and diagnosing chronic renal insufficiency. In this study, seventy cases with chronic renal insufficiency from Jun. 2010 to Oct. 2013 were selected as the observation group. Meanwhile, another 70 volunteers with normal renal functions were set as the control group. The level of BMD, PTH, CT and 25(OH)-Vit were detected by using ELISA assay. DPX bone density meters (UNIGAMMA X-RAY PLUS) were used for the detection of BMD. The results indicated that BMD levels of the proximal femur (include Troch, Shaft, Total, Neck, Ward) and lumbar vertebra in the observation group were significantly lower while the PTH and CT were significantly higher compared with the control group (P<0.05). A positive correlation was identified between the serum creatinine (Scr) concentrations and CT, PTH, while the correlation with 25(OH)-Vit was considered to be negative. In conclusion, the BMD, PTH, CT, and 25 (OH)-Vit would provide reference in diagnosing and treatment for chronic renal insufficiency. These indexes would be important clinical significance for screening and early diagnose of osteoporosis in these patients. PMID- 26131191 TI - RhoBTB2 (DBC2) functions as a multifunctional tumor suppressor in thyroid cancer cells via mitochondrial apoptotic pathway. AB - Thyroid cancer is the most common endocrine malignancy worldwide. Tumor suppressor gene RhoBTB2 (also known as Deleted in Breast Cancer 2, DBC2) was observed in various carcinomas, however, no reports showed the effects of RhoBTB2 on thyroid cancer. In our study, we found that RhoBTB2 decreases proliferation, increases apoptosis, inhibits mobility, and induces mitochondria damage in SW579 cells through increased Bax and decreased Bcl-2 and Bcl-xL protein expression. The effects of RhoBTB2 on SW579 cells were inversed by using butin (an inhibitor of the mitochondrial apoptosis pathway). Our results suggest that RhoBTB2 suppresses the growth of SW579 cells through a mitochondrial apoptosis pathway. PMID- 26131192 TI - The effects of tranexamic acid and 6% hydroxyethyl starch (HES) solution (130/0.4) on postoperative bleeding in coronary artery bypass graft (CABG) surgery. AB - BACKGROUND: The addition of 6% hydroxyethyl starch (HES) into Ringer lactate priming solution may have adverse effects on hemostasis in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) with or without the use of tranexamic acid. METHODS: In a prospective, randomized clinical trial, 132 patients were assigned to receive 20 ml/kg of Ringer priming solution with or without tranexamic acid (TA) (Group RS-TA, n=34 and Group RS noTA, n=32) or 10 ml/kg of 6% HES plus 10 ml/kg of RS priming solution with or without intravenous tranexamic acid (Group HES-TA, n=35 and Group HES-noTA, n=31). Estimated blood loss, chest tube drainage, amount of blood products, hemoglobin, hematocrit, platelet and coagulation parameters were examined before and 24 hour after surgery. RESULTS: For Group HES with tranexamic acid, when compared to other groups, estimated blood loss, postoperative 24 hour drainage loss and blood product transfusions were less (P=0.023; P=0.003; P=0.001; respectively) and hemoglobin, hematocrit values at 12 and 24 hours after surgery increased in comparison to other groups (P=0.041, P=0.034, P=0.004, P=0.001; respectively). Platelet concentrations were similar between groups (P>0.05). CONCLUSIONS: In CABG, the administration of tranexamic acid in HES 130/0.4 prime solution study group decreased estimated blood loss and chest tube drainage in comparison to patients receving Ringer prime solution with or without tranexamic acid postoperatively however, no effects on renal functions or postoperative complications were shown. PMID- 26131193 TI - Transcutaneous electric acupoint stimulation at Jiaji points reduce abdominal pain after colonoscopy: a randomized controlled trial. AB - BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) at Jiaji acupuncture points has therapeutic potential for relieving viscera pain and opioid-related side effects. This prospective, randomized, triple-blinded, placebo-controlled trial was to investigate the efficacy of TEAS on abdominal pain after colonoscopy. METHODS: Consecutive outpatients with American Society of Anesthesiologists (ASA) physical status I or II underwent selective colonoscopy were randomly assigned into two groups for either TEAS or sham pretreatment. The primary outcomes were the incidence of abdominal pain after colonoscopy. The secondary outcomes included the incidence of abdominal distension, postoperative nausea and vomiting (PONV), duration of PACU stay, and patient's satisfaction and acceptance. RESULTS: Among the 229 patients analyzed, fewer occurrence of post procedural abdominal pain (11.4% vs 25.2%, P = 0.007) and distension (1.8% vs 7.8%, P = 0.032) were observed in TEAS group, when compared with the sham group. The duration of PACU stay was significant shortened in TEAS group (P < 0.001). Meanwhile, patients' satisfaction score to medical service was higher (P < 0.001), and their acceptance to colonoscopy was improved (P = 0.011). CONCLUSION: Pretreatment with TEAS can reduce post-procedural discomfort, provide more efficient medical resources utilization, and improved patient's satisfaction and colonoscopy acceptance. PMID- 26131194 TI - Impact of 3'UTR genetic variants in PCSK9 and LDLR genes on plasma lipid traits and response to atorvastatin in Brazilian subjects: a pilot study. AB - BACKGROUND: Hypercholesterolemia is a complex trait, resulting from a genetic interaction with lifestyle habits. Polymorphisms are a major source of genetic heterogeneity, and variations in 2 key cholesterol homeostasis genes; low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type-9 (PCSK9), lead to dyslipidemia. So, we investigated the relation of 2 variants located in the 3'-UTR (3'-untranslated region) of LDLR (rs14158, G>A) and PCSK9 (rs17111557, C>T) with lipid profile and atorvastatin response. METHODS: SNP influence on lipid profile was assessed in hypercholesterolemic patients (HC; n = 89) using atorvastatin (10 mg/day/4 weeks) and in normolipidemic subjects (NL; n = 171). Genotyping was completed through real-time PCR using TaqMan assays. RESULTS: rs14158 G allele was higher in HC than in NL group (P = 0.043). NL subjects carrying the T allele of the PCSK9 variant had lower high-density lipoprotein cholesterol (HDL-c) than C allele carriers (P = 0.009). There was no association between LDLR and PCSK9 SNPs and atorvastatin response. Additionally, the PCSK9 variant creates a microRNA interaction site, which could implicate an epigenetic mechanism in PCSK9-dependent HDL-C regulation. CONCLUSIONS: The rs14158 SNP contributes to hypercholesterolemia. Also, a putative microRNA regulation may influence HDL-C variability observed in rs17111557 carriers. Cholesterol-lowering response to atorvastatin is not influenced by LDLR and PCSK9 variants. PMID- 26131195 TI - Correlation of serum liver fibrosis markers with severity of liver dysfunction in liver cirrhosis: a retrospective cross-sectional study. AB - Hyaluronic acid (HA), laminin (LN), amino-terminal pro-peptide of type III pro collagen (PIIINP), and collagen IV (CIV) are four major serum markers of liver fibrosis. This retrospective cross-sectional study aimed to evaluate the correlations of the four serum markers with the severity of liver dysfunction in cirrhotic patients. Between January 2013 and June 2014, a total of 228 patients with a clinical diagnosis with liver cirrhosis and without malignancy underwent the tests of HA, LN, PIIINP, and CIV levels. Laboratory data were collected. Child-Pugh and model for the end-stage of liver diseases (MELD) scores were calculated. Of them, 32%, 40%, and 18% had Child-Pugh class A, B, and C, respectively. MELD score was 7.58+/-0.50. HA (coefficient r: 0.1612, P=0.0203), LN (coefficient r: 0.2445, P=0.0004), and CIV (coefficient r: 0.2361, P=0.0006) levels significantly correlated with Child-Pugh score, but not PIIINP level. Additionally, LN (coefficient r: 0.2588, P=0.0002) and CIV (coefficient r: 0.1795, P=0.0108) levels significantly correlated with MELD score, but not HA or PIIINP level. In conclusions, HA, LN, and CIV levels might be positively associated with the severity of liver dysfunction in cirrhotic patients. However, given a relatively weak correlation between them, our findings should be cautiously interpreted and further validated. PMID- 26131196 TI - Life quality changes within 26 month after the non-surgical treatment in patients with deep vein thrombosis. AB - OBJECTIVE: The objective of this study is to investigate the life quality of lower-extremity deep vein thrombosis (DVT) patients 26 m after progressive decompression elasticity socks therapy. METHODS: SF-36 scale was used to record the life quality scores in 74 patients with acute and subacute deep venous thrombosis, all the patients received the non-surgical treatment. The eight dimensions of life quality variation were documented and analyzed. RESULTS: The baseline data were comparable (P = 1.000 for age, P = 0.655 for sex). At the time of admission and at different time points after discharge, there were significant differences for eight dimensions in patients with deep vein thrombosis (Ps < 0.001). In addition that eight dimensions scores were significantly different between the score at 2 months, 4 months after discharge and the score at certain individual stages (Ps < 0.05), there were no significant difference for eight dimensions scores at different stages (Ps > 0.05). CONCLUSIONS: Showed slow improvement within six months of deep vein thrombosis in patients with non surgical treatment, the life quality scores entered the plateau stage, the life quality of the RP and the PF dimension were slightly impaired, the VT dimension showed relatively obvious damage, the remaining dimensions can recover to healthy levels. The blood circulation activation drugs may help maintain the stability of life quality and delay the occurrence of PTS. The turning point of life quality did not show and required extended follow-up period. PMID- 26131197 TI - Evaluation of tobacco use on Chinese population through ATTOC model: a cross sectional survey on hospitalized psychiatric patients. AB - OBJECTIVES: To evaluate the feasibility of Addressing Tobaccos through Organizational Change (ATTOC) intervention to Chinese psychiatric patients, and to better address tobacco use through the ATTOC intervention model in the context of China. METHODS: The study was conducted in Mental Health Center of West China Hospital in 2010. A total of 100 hospitalized psychiatric patients were recruited to carry out ATTOC intervention. Subjects suffers from mental illness were diagnosed by professional psychiatrists according to the International Statistical Classification of Diseases (ICD-10) criteria. RESULTS: The prevalence of tobacco use in hospitalized psychiatric patients were closely correlated with the type of mental illness, family smoking history, sex, age, marital status, education status, etc. However, most psychiatric patients knew little about these, and tended to ignore the importance of smoking cessation. CONCLUSIONS: The ATTOC intervention program of the U.S. may be suitable for hospitalized Chinese psychiatric patients, and it could be applied for the tobacco smoking treatment in China. However, the health effects of tobacco use still did not draw amount attentions from both the clinicians and general public. It is urgently needed to raise people's awareness and carry out ATTOC intervention to control tobacco use, and ultimately terminate tobacco use. PMID- 26131198 TI - Intratympanic dexamethasone injections for refractory Meniere' s disease. AB - Intratympanic injections or titration is a potential medical therapeutic strategy for patients with incurable inner ear diseases. Dexamethasone represent an attractive steroid source in intratympanic steroids strategies in the treatment of inner ear disorders. Here, we evaluated the effectiveness of intratympanic dexamethasone injections (IDI) in outpatients with refractory Meniere's disease (MD). Vestibular function measured by Vestibular Ocular Reflex (VOR) gain and caloric test revealed that 21 outpatients out of 43 (48.8%) had complete sufficient vertigo control, while 9 (20.9%) of them were attached to fundamental manipulation. Out of the 13 remaining outpatients, 4 (9.3%) had a limit control and 9 had less modification. Therefore, 5 of 9 received re-treatment with IDI and 2 of 9 patients were administered ablative treatment with gentamicin. Meanwhile, audiology data suggested that 3 (7.0%), 4 (9.3%), 32 (74.4%), 4 (9.3%) patients were attached to the level of A, B, C, D, respectively. Furthermore, the symptom of tinnitus in 5 outpatients vanished, 21 (48.8%) diminished, 10 (23.3%) invariable, 7 (16.3%) aggravated. In 4 of 24 cases (16.7%), aural fullness disappeared after IDI, when the aural fullness was alleviated in 11 cases (45.8%) even intensive in 9 patients (37.5%). Together, our results demonstrate that intratympanic dexamethasone injection, as an effective therapeutic strategy for refractory Meniere's disease, could either be used for cascade therapy preoperation or used for patients who couldn't accept the surgery. PMID- 26131200 TI - Laparoscopic TME associated with neoadjuvant chemoradiation towards aggressive colorectal cancer. AB - OBJECTIVE: This study aims to investigate the clinical synchronization of the neoadjuvant chemoradiation (NC) and the laparoscopic total mesorectal excision (TME) in the treatment of locally aggressive colorectal cancer (LACC). METHODS: 92 LACC patients were selected for the research, among who 46 cases, who were performed the synchronized NC, were divided into the treatment group, after having rest for 4-6 weeks after the treatment, the 40 patients of the treatment group, who were performed the laparoscopic surgery, formed the laparoscopy group. The rest 46 patients were divided into the control group, who were performed the conventional treatment. The intraoperative conditions, postoperative recoveries, postoperative complications and recurrence rates of the two groups were compared. RESULTS: The stage-declining rate of the treatment group was 67.3%, and the surgical resection rate, anal preservation rate and postoperative complications were 86.9%, 69.6% and 26%, respectively, which were significantly higher than the control group; while the long-term recurrence rate significantly decreased to 21.7%, and the difference was statistically significant (P<0.05). CONCLUSION: The NC could effectively achieve the stage-declining purpose against the LACC, improve the resection rate and reduce the postoperative recurrence rate. PMID- 26131199 TI - Clinicopathologic significance and survival of TIP30 expression in laryngeal squamous cell carcinoma. AB - BACKGROUND: The expression and clinical significance of TIP30 and p53 in laryngeal squamous cell carcinoma (LSCC) have not been investigated. METHOD: We determined immunohistochemically the expression of TIP30 and p53 in surgical specimens from 105 patients with LSCC. Survivals were estimated using the Kaplan Meier method. RESULTS: TIP30 protein expression in LSCC patients was significantly less in tumor tissues than that of adjacent normal tissues (46.7% vs. 79.0%), while p53 protein expression was significantly increased in LSCC (15.2% vs. 63.8%) compared with adjacent normal tissues. The TIP30 expression levels were also significantly correlated with tumor stage, differentiation, and the presence of lymph nodes. The expression of TIP30 was significantly negatively correlated with that of p53 (r = -0.249, P = 0.010). LSCC patients with lower expression level of TIP30 had a significantly higher recurrence and worse overall survival than those with elevated TIP30 expression (P = 0.014 and P = 0.040, respectively). Furthermore, multivariable analysis found that patients with high expression of TIP30 had a greater than approximately 2.2-fold increased risk for death overall or recurrence than those with low expression of TIP30, supporting that down-regulation of TIP30 expression in tumors may involve in development and progression and predict poor prognosis of patients with LSCC. CONCLUSION: Our results may suggest that down-expression of TIP30 is closely related to carcinogenesis, progression, biological behavior, and prognosis of LSCC. PMID- 26131201 TI - GPIbalpha reflects the development and progress of the patients with severe preeclampsia. AB - Preeclampsia (PE) is a pregnancy-specific syndrome that occurs in a previously normotensive woman. Some data suggested that the activation parameters of platelets in preeclampsia. The aim of this study is to determine whether the levels of GPIbalpha and GPIIb for patients with preeclampsia were enhanced after cesarean section. In this study, detecting levels of GPIbalpha and GPIIb by flow cytometry (FCM). The venous blood of 48 severe preeclampsia women, 16 mild preeclampsia and 22 normotensive women, were collected before operation and 72 hours after the operation. Blood samples were obtained also from 20 non-pregnant women. RESULTS: The level of GPIbalpha of the normotensive pregnancy was lower than the control group, but there was no significance (P > 0.05). The level of GPIbalpha of the severe preeclampsia group was much lower than other groups (P < 0.01). In the severe preeclampsia group, the level of GPIbalpha of postoperative patients was higher than preoperative patients (P < 0.01). There was no significance of GPIIb levels between each group (P > 0.05). In conclusion, GPIbalpha was an important index of reflecting the change of severe preeclampsia. Detecting the levels of GPIbalpha plays an important role in observing the development of this disease and guiding clinical treatment. PMID- 26131202 TI - Genetic association of NQO1 609C>T polymorphism with risk of gastrointestinal cancer: evidence from case-control studies. AB - BACKGROUND: Numerous studies have evaluated the association between NQO1 609C>T polymorphism and gastrointestinal (GI) cancer. However, the results remain inconclusive. To obtain a more precise estimation of the relation, we conducted an analysis of all available case-control studies. METHODS: Eligible studies were identified by searching the databases and finally 19 articles were included in the meta-analysis. Odds ratio (OR) with 95% confidence interval (95% CI) was applied to assess the association between NQO1 609C>T polymorphism and GI cancer risk. Z test was used to evaluate the significance of OR and 95% CI. RESULTS: In the overall analysis, there existed a significant association between NQO1 609C>T polymorphism and GI cancer susceptibility (T vs. C: OR = 1.07, 95% CI = 1.01 1.14). The subgroup analysis based on ethnicity showed that NQO1 609C>T polymorphism was associated with susceptibility to GI cancer in mixed population (TT vs. CC: OR = 2.21, 95% CI = 1.44-3.40; TT vs. CT + CC: OR = 2.26, 95% CI = 1.48-3.44; Allele T vs. Allele C: OR = 1.24, 95% CI = 1.05-1.47). For the subgroup analysis according to source of control, a remark relationship of 609C>T with increased risk of GI cancer was observed in HB population (Allele T vs. Allele C: OR = 1.07, 95% CI = 1.01-1.14). CONCLUSION: Our results demonstrated that NQO1 609C>T polymorphism might be associated with susceptibility to GI cancer. PMID- 26131203 TI - Repair of osteochondral defects by mosaicplasty and allogeneic BMSCs transplantation. AB - OBJECTIVE: To investigate the feasibility and efficacy of repairing osteochondral defects with mosaicplasty and allogeneic bone marrow mesenchymal stem cells (BMSCs) transplantation. METHODS: BMSCs were harvested from rabbits and maintained in vitro. Cells of third passage were mixed with pluronic F-127. Osteochondral defect animal model was established in rabbits and then this defect was treated with autologous osteochondral grafts with or without BMSCs above mentioned. In control group, pure pluronic F-127 was filled in the defect. Histological and immunohistological examinations were performed for the evaluation of therapeutic effectiveness. RESULTS: Autologous osteochondral grafts in both groups were not loose, prolapsed and depressed. In BMSCs group, the tissues in the "death space" became hyaline cartilage. The arrangement of chondrocytes was regular. At 4, 8, 12 and 16 weeks, O'Driscoll and Keeley and Salter score were 14.00+/-1.00, 16.75+/-1.71, 18.00+/-0.82 and 20.50+/-1.29 in BMSCs group, which were significantly higher than those in control group (7.67+/ 0.58, 8.00+/-0.82, 8.50+/-0.58 and 9.00+/-0.82, respectively). There were significant differences among different treatments (F=584.028, P=0.000), but the score was comparable between right defect and left defect (F=0.028, P=0.890). In addition, significant difference was also observed at different time points (F=18.364, P=0.000), but there was no interaction between time and treatment (F=6.939, P=0.015). Moreover, interactions among other factors were also not observed. CONCLUSION: Mosaicplasty and BMSC transplantation are effective to repair the osteochondral defects and integrate the "death space", achieving a better therapeutic efficacy. Thus, this combined therapy may become an effective strategy for the therapy of osteochondral defects. PMID- 26131204 TI - The effect of disease control on mean platelet volume and red blood cell distribution in patients with acromegaly. AB - OBJECTIVES: Several studies have shown increased atherogenic risk factors and biomarkers of inflammation and atherosclerosis in association with growth hormone excess. Mean platelet volume (MPV) and red blood cell distribution (RDW) are currently gaining interest as new independent cardiovascular risk factors. The aim of this study was to evaluate the effect of disease control on MPV and RDW in acromegaly patients. MATERIALS AND METHODS: We retrospectively enrolled 36 acromegaly patients (23 males, 13 females; mean age 41.94 +/- 11.55). Patients were divided into two groups: disease controlled by surgical treatment alone (group A) or by somatostatin analog (SSA) therapy (group B). MPV and RDW measurements were evaluated during active and inactive disease periods in the two groups. RESULTS: There were statistically significant increases in MPV and RDW in patients receiving SSA therapy (P = 0.012 and P = 0.020, respectively). The differences in MPV and RDW changes in patients receiving surgical treatment alone were not statistically significant (P=0.364 and P=0.339, respectively). CONCLUSIONS: This is the first report on the evaluated the effect of disease control on MPV and RDW in acromegaly patients. Our study results showed that MPV and RDW measurements are significantly increased in acromegaly patients with disease controlled by SSA therapy. Therefore, acromegalic patients treated with SSAs may have increased cardiovascular risk based on an increase in MPV and RDW. PMID- 26131205 TI - Correlation of HLA-DQB1 gene polymorphism of Xinjiang Uygur with outcome of HBV infection. AB - BACKGROUND: The aim of this study was to explore the correlation of gene polymorphisms of human leukocyte antigen-DQB1 (HLA-DQB1) with the infection outcome and replication status of hepatitis B virus (HBV) positive patients in the Xinjiang Uygur population in China. METHODS: 110 cases of chronic hepatitis B (CHB) of Xinjiang Uygur were examined clinically, which were named as the CHB group; 100 cases carrying chronic HBV (ASC) served as ASC group; 80 cases of self limited HBV infection (RHBS) were recorded as RHBS group. Genotypes of HLA-DQB1 were detected by sequence specific primer-polymerase chain reaction (PCR-SSP) method, and the differences of gene frequency among groups were also compared. The distribution frequencies of the HLA-DQB1 gene under different replication states of HBV were compared. RESULTS: The distribution frequency of DQB1*0201 in the RHBS group was higher than that of the ASC group (18.75%, 10.50%, chi(2) = 5.959, P < 0.05, OR = 2.257). The distribution frequency of DQB1*0201 in the CHB group was higher than that of the ASC group (17.73%, 10.50%, chi(2) = 5.363, P < 0.05, OR = 2.066). The distribution frequency of DQB1*0301 in the CHB group was higher than that of the ASC group (26.82%, 16.50%, chi(2) = 9.062, P < 0.05, OR = 2.349). The distribution frequency of DQB1*0303 in the CHB group was lower than that of the ASC group (19.55%, 31.00%, chi(2) = 10.996, P < 0.05, OR = 0.393). There was no statistically significant difference in the allele frequencies among all other groups. The distribution frequency of DQB1*0201 in the low replication group was higher than that of the high replication group (17.08%, 10.56%, chi(2) = 4.295, P < 0.05, OR = 1.939). CONCLUSION: HLA-DQB1*0201 is a HBV resistance gene in Xinjiang Uygur. DQB1*0301 is correlated with continuous infection of HBV. DQB1*0303 is a susceptibility gene of ASC. PMID- 26131206 TI - The expression of EBV-encoded LMP1 in young patients with lupus nephritis. AB - One of the major disease manifestations of systemic lupus erythematosus (SLE) is lupus nephritis (LN), and the underlying mechanisms are not yet understood. Epstein-Barr virus (EBV) reactivation was associated with the induction of SLE, with EBV-encoded latent membrane protein1 (LMP1) plays a vital role in this process. Although it was reported that LN was associated with LMP1, most of these results are from patients with ages differed greatly (range, 10-56 years). Given the increased prevalence of EBV infection in young patients, we focused on the association of LN and LMP1 expression in the renal tissues of young patients (range, 6-16 years) in this study. We found that the positive rate of LMP1 in the renal tissues was significantly higher in patients with LN compared with control (P<0.001), which is consistent with the previous reports. The positive rates of LMP1 were similar between the patients of initial onset and relapse, and there was no detectable difference between the patients with and without concurrent infection (P>0.05). However, we reported for the first time about the positive correlation of LMP1 with classification of LN. The proportion of young patients positive for anti-Sm antibody was significantly higher in the LMP1 positive group compared with the LMP1 negative control (P>0.05). These results indicate that EBV infection in the renal of young patients may lead to the increased severity of LN, and the expression of anti-Sm is likely contributed to this process. PMID- 26131207 TI - Clinical observation of atrial threshold monitoring algorithm: a single center experience. AB - OBJECTIVE: To observe the atrial capture management in an atrial threshold monitoring algorithm. By calculating the enabling rate of the atrial threshold monitoring algorithm and comparing atrial thresholds measured automatically and manually, we evaluate its safety, reliability and applicability in clinical practice. METHODS AND RESULTS: Data were collected at implant, start of atrial threshold monitoring, visits scheduled 1 month, 2 months and 4 months thereafter, and upon notification of adverse events. Atrial threshold monitoring algorithm was enabled in 94 patients, while in 38 not, indicating an enabling rate of 71.2%. Causes of the unsuccessful attempts to enable automatic atrial threshold include tachycardia (2, 5.3%), and atrial safety margin not met (36, 94.7%). A total of 88 pairs of atrial thresholds measured automatically and manually were gained. The auto threshold was 0.528 +/- 0.270 V, and the manual threshold was 0.580 +/- 0.223 V. There is a strict correlation between the automatic measurements and those conducted manually by the physician with a P < 0.05. No significant differences were observed during the 1-month, 2-month and 4-month follow-up. CONCLUSION: Atrial threshold monitoring algorithm is safe, reliable and applicable over time. Atrial threshold monitoring tested atrial threshold was demonstrated to be clinically equivalent to the manual atrial threshold test. The addition of atrial threshold monitoring will benefit the patients by reducing energy cost and enhancing pacemaker safety. PMID- 26131208 TI - Inverse correlation between serum adiponectin and 8-iso-prostaglandin F2alpha in newly diagnosed type 2 diabetes patients. AB - This study was set out to determine the association of serum adiponectin and oxidative stress in newly diagnosed type 2 diabetes patients. 106 patients with newly diagnosed type 2 diabetes were recruited. Simultaneously scanning of the extracranial carotid arteries, common iliac arteries and femoral arteries were performed for measurement of intima media thickness (IMT) in all subjects. Atherosclerotic plaque was defined as IMT value >1.3 mm. The serum levels of adiponectin and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a marker of oxidative stress, were examined by enzyme-linked immunosorbent assay. Metabolic parameters were detected by clinical chemistry. According to the results, all of 106 patients with type 2 diabetes were newly diagnosed within 12 months, and aged 60.68+/-4.32 years. The level of serum adiponectin in newly diagnosed type 2 diabetes patients was lower than that in healthy subjects. Furthermore, type 2 diabetes patients with atherosclerotic plaques had lower serum adiponectin level than those without atherosclerotic plaques. Serum 8-iso-PGF2alpha level in newly diagnosed type 2 diabetes patients was higher than that in healthy subjects. Further analyses showed that serum adiponectin level was reversely associated with serum 8-iso-PGF2alpha in newly diagnosed type 2 diabetes patients. Additionally, the atherosclerotic plaques in newly diagnosed type 2 diabetes patients were positively correlated with total cholesterol, but negatively correlated with serum adiponectin level. Taken together, this study suggests that in newly diagnosed type 2 diabetes, serum adiponectin levels are probably associated with oxidative stress and also with the severity of atherosclerosis. PMID- 26131209 TI - Dezocine attenuates fentanyl-induced cough in a dose-dependent manner-a randomized controlled trial. AB - Fentanyl-induced cough (FIC) should be effectively prevented in patients requiring stable induction of general anesthesia. Our study was to evaluate the suppressive effects of different doses of intravenous dezocine on FIC during the induction of general anesthesia. A total of 400 patients of American Society of Anesthesiologists (ASA) physical status I and II were randomized into four groups (n = 100). Right before Fentanyl bolus, the four groups were given intravenously a matching placebo (group I) (equal volume of 0.9% saline), dezocine 0.025 mg/kg (group II), 0.05 mg/kg (group III), and 0.1 mg/kg (group IV), respectively. Patients were induced with fentanyl 3 ug/kg and the injection time of fentanyl was less than 5 s in all patients. The occurrence of cough was recorded 2 min after fentanyl bolus. The incidence of FIC was 40% in group I, 12% in group II, 4% in group III, and 0 in group IV. Group I had significantly higher incidence of FIC than Groups II, III and IV (P < 0.05). Group IV had lower incidence of FIC than Groups II (0% vs 12%; P = 0.0003) and III (0% vs 4%; P = 0.043). Our study showed that intravenous dezocine reduced the incidence of FIC during anesthetic induction. The suppressive effect was dose-dependent. PMID- 26131210 TI - Magnetic resonance imaging on disc degeneration changes after implantation of an interspinous spacer and fusion of the adjacent segment. AB - The aim of the study was to investigate the changes of the lumbar intervertebral disc degeneration by magnetic resonance imaging (MRI) after the implantation of interspinous device and the fusion of the adjacent segment. A total of 62 consecutive patients suffering L5/S1 lumbar disc herniation (LDH) with concomitant disc space narrowing or low-grade instability up to 5 mm translational slip in L5/S1 level were treated with lumbar interbody fusion (LIF) via posterior approach. Thirty-four of these patients (Coflex group) received an additional implantation of the interspinous spacer device (CoflexTM) in the level L4/L5, while the rest of 28 patients (fusion group) underwent the fusion surgery alone. Clinical and radiographic examinations were performed at pre- and postoperative visits to compare the clinical outcomes and the changes of the L4/L5 vertebral disc degeneration on MRI in both Coflex and fusion group. Although both Coflex and fusion group showed improvements of the clinical outcomes assessed by the Oswestry Disability Index (ODI) after surgery, patients in Coflex group had more significant amelioration (P < 0.05) compared to fusion group. During follow up, the postoperative disc degeneration changes in Coflex group assessed by the relative signal intensity (RSI) differed from those in fusion group (P < 0.05). The supplemental implantation of CoflexTM after the fusion surgery could delay the disc degeneration of the adjacent segment. PMID- 26131211 TI - Effects of hydrosalpinx on ultrasonographic parameters for endometrial receptivity during the window of implantation measured by power color Doppler ultrasound. AB - AIM: The aim of this study is to assess the effects of hydrosalpinx on ultrasonographic parameters for endometrial receptivity during the window of implantation, as measured by power color Doppler ultrasound. METHODS: The women recruited to this study included sixty with unilateral or bilateral hydrosalpinx and fifty-seven prior to in vitro fertilization-embryo transfer (IVF-ET) or artificial insemination (AI) performed due to male infertility. Ultrasonographic parameters for endometrial receptivity were measured during the window of implantation by power color Doppler ultrasound. RESULTS: The proportion of triple line endometrial pattern and uterine contractions from the cervix to the fundus were significantly lower in the hydrosalpinx group than in the control group. In addition, patients in the hydrosalpinx group had a significantly lower pulsatility index (PI) of uterine spiral arteries. There were no significant differences in endometrial thickness, subendometrial blood flow distribution pattern, uterine artery PI, uterine artery resistance index (RI), or uterine spiral artery RI between the two groups. CONCLUSIONS: Hydrosalpinx may be involved in the regulation of endometrial receptivity through its influence on endometrial pattern, uterine contractions, and PI of the uterine spiral arteries. PMID- 26131212 TI - Association of SLCO1B1 gene polymorphisms with toxicity response of high dose methotrexate chemotherapy in childhood acute lymphoblastic leukemia. AB - OBJECTIVE: The present study aims to investigate the correlation of polymorphisms of SLCO1B1 gene with the toxicity during therapy with the high-dose methotrexate (MTX) chemotherapy in childhood acute lymphoblastic leukemia. METHODS: We analyzed 2 polymorphisms (rs4149081 and rs11045897) in SLCO1B1 gene in 280 Chinese pediatric B-ALL patients, using MTX plasma concentration as an objective and quantifiable marker of toxicity. We utilized Enzyme-multiplied immunoassay technique (EMIT) to measure the plasma concentration of MTX. The polymerase chain reaction-allele specific (PCR-AS) method was utilized to perform the genotyping. RESULTS: We found there was a statistically significant association between MTX plasma concentration and the SLCO1B1 rs11045879 CC genotype (P<0.05). We also found the rs4149081 AA genotype was associated with high-MTX plasma concentrations. A-C haplotype carriers have a higher risk for MTX delayed clearance but G-T haplotype was associated with a lower risk for MTX delayed clearance. CONCLUSIONS: The rs4149081 AA genotype and the rs11045897 CC genotype could be indicators for high-MTX plasma concentrations in children with ALL. PMID- 26131213 TI - Effect of variation of FGF2 genotypes on the risk of osteosarcoma susceptibly: a case control study. AB - OBJECTIVE: Genetic factors play an important role in osteosarcoma (OS) etiology and fibroblast growth factor 2 (FGF2) gene single polymorphisms may be involved. The aim of this study was to test whether FGF2 variants are associated with susceptibility to OS in a Chinese population. METHODS: A total of 151 subjects who were diagnosed as OS and 225 healthy age-matched controls were enrolled in the present study. Thers11737764 C/T SNP in FGF2 gene was genotyped in all the subjects. The SPSS software was used to investigate the association between the rs11737764 genotypes and OS susceptibility or severity. RESULTS: The genotype frequencies of the FGF2 rs11737764 C/T polymorphism were 44.4% (CC), 50.3% (CT) and 5.3% (TT) in OS patients, and 55.6% (CC), 43.1% (CT) and 1.3% (TT) in controls. Rs11737764 C/T was found to be significantly associated with increased risk and OS no matter what genetic model was used. CONCLUSION: In conclusion, our data demonstrated the FGF2 SNP rs11737764 was significantly associated with increased osteosarcoma susceptibility in Chinese Han Population. PMID- 26131214 TI - Neuroanatomical evidence of the melanocortin-4 receptor expression in the mesencephalic periaqueductal gray innervating renal tissues. AB - To determine the neuronal connections in the periaqueductal gray (PAG) is important for studying modulation of neuronal activity of PAG to influence sympathetic responses. We had characterized projections from the left kidney to the midbrain PAG in adult male melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) transgenic mice by using retrograde tracing techniques of pseudorabies virus (PRV)-614 for direct visualization under two-photon immunofluorescence microscope. We found that injections of PRV-614 into the kidney resulted in retrograde infection of neurons in the ventrolateral sub-areas of PAG, and PRV-614/MC4R-GFP double-labeled neurons were detected in the ventrolateral sub-areas of PAG. These results indicated that a subpopulation of ventrolateral PAG neurons innervating renal tissues expressed MC4R, suggesting that deep brain stimulation of the ventrolateral PAG may influence renal function by melanocortinergic pathway. PMID- 26131215 TI - Relation between ADIPOQ gene polymorphisms and type 2 diabetes in a Chinese population. AB - OBJECTIVE: We aimed to investigate the relation between adiponectin gene (ADIPOQ) polymorphisms and type 2 diabetes mellitus (T2DM) in a Chinese population. METHODS: The present study included 510 subjects with normal glucose tolerant (NGT) and 510 patients with type 2 diabetic. Five SNPs (rs2241767, rs3821799, rs182052, rs1501299 and rs7627128) were genotyped by TaqMan methods. RESULTS: Of these 5 SNPs, three SNPs (rs1501299, rs182052, and rs7627128) were found to be significantly associated with T2DM. The haplotypes AAT (Construction of rs1501299, rs182052, and rs7627128) was frequent in T2DM patients (OR=2.051, 95% CI: 1.439~2.923, P<0.001), but GAT (Construction of rs1501299, rs182052, and rs7627128) was frequent in the control group (OR=0.65, 95% CI: 0.540~0.805, P<0.001). CONCLUSION: The ADIPOQ gene variants and haplotype were associated with the risk for development of type 2 diabetes. PMID- 26131216 TI - Research of the heteroresistance of Pseudomonas aeruginosa to imipenem. AB - Pseudomonas aeruginosa (PA) plays plays an important role in nosocomial infection. To explore the heteroresistance of PA to imipenem (IMP), we detected the sensitivity of 140 strains of PA to IMP using the KB method and VITEK method. Combined with resistance mutation analysis, the heteroresistance of PA to IMP was determined. Whilst, the double disk synergy test and SYBGreen RT-PCR for efflux pump were performed in IMP-heteroresistant PA strains. In this study, we confirmed 20 IMP-heteroresistant strains. The double disk synergy tests suggested that none of 20 heteroresistant PA strains produced metalloenzyme. The SYBGreen quantitative RT-PCR revealed that the MexAB expression level of efflux pump in IMP-heteroresistant PA was significantly higher than that in the IMP-sensitive strains (P<0.05), while there was no significantly different between the MexCD expression between resistant strains and sensitive strains (P<0.05). We believe that the clinicians should pay more attention to the PA heteroresistance to IMP, and the heteroesistance of PA to IMP is related to high expression in the MexAB of PA efflux pump. PMID- 26131217 TI - Alterations in lipid profile, oxidative stress and hepatic function in rat fed with saccharin and methyl-salicylates. AB - BACKGROUND: Food additives attract consumers, improve foods quality, control weight, and replace sugar in foods, while it may affect seriously children and adults health. AIM: To investigate the adverse effects of saccharin and methylsalicyltaes on lipid profile, blood glucose, renal, hepatic function, and oxidative stress/antioxidant (lipid peroxidation, Catalase and reduced glutathione (GSH) in liver tissues). METHODS: 46 young male albino rats were used. Saccharin and methylsalicylate were giving orally as low and high dose for 30 days. Rats were divided into 5 groups, 1(st) control group, 2(nd) and 3(rd) low and high saccharin-treated groups and 4(th) and 5(th) low and high methylsalicylate-treated group. RESULTS: Serum total cholesterol, triglyceride, glucose levels and body weight gain were decreased in saccharin high dose compared to control. Rats ingested high dose of saccharin presented a significant reduction in serum triglycerides, cholesterol and LDL levels. Low and high doses of saccharin exhibited a significant increase in liver function marker of ALT, AST, ALP activity, total proteins and albumin levels and renal function test (urea and creatinine levels) in comparison with control group. Saccharin high dose induce a significant decline in hepatic GSH levels, catalase and SOD activities while increased in hepatic MDA level. CONCLUSION: It could be concluded that, saccharin affects harmfully and alters biochemical markers in hepatic and renal tissues not only at greater doses but also at low doses. Whereas uses of metylsalicylates would not pose a risk for renal function and hepatic oxidative markers. PMID- 26131218 TI - Clinical efficacy of Yingliu treatment for Graves disease. AB - OBJECTIVE: To observe the clinical efficacy and safety of the traditional Chinese medicine (TCM) mixture Yingliu combined with methimazole medication for the treatment of Graves disease (GD). METHOD: In a randomized, paralleled control study, 92 GD patients were randomized into a Yingliu mixture treatment and a control treatment group, both receiving methimazole. Both treatments lasted for 12 weeks and outcome parameter were thyroid function, thyroid autoantibodies, TCM symptome scores and safety indicators. RESULTS: The clinical efficiency of the Yingliu mixture-methimazole combination was 92.5% vs. 82.5% (P < 0.05) of the solely methimazole medication group. After 12 weeks treatments the Yingliu mixture in combination with methimazole improved free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH) receptor antibody (TRAb) and thyroglobulin antibody (TGAb) values significantly more than methimazole alone and TCM symptome scores were significant lower after 12 week treatment in the Yingliu mixture- methimazole group (P < 0.05). The thyroid enlargement (21 vs. 10, P < 0.05), fatigue (39 vs. 30, P < 0.01) and dry mouth symptoms (37 vs. 29, P < 0.05) were superior improved in the Yingliu than in the control medication group, respectively. There was no significant difference regarding safety evaluations between both treatment groups (P = 0.499). CONCLUSION: Yingliu mixture as combined medication with methimazole can significantly improve the outcome of a solely methimazole application for GD treatments. PMID- 26131219 TI - Complications and risk factors for mortality in penetrating abdominal firearm injuries: analysis of 120 cases. AB - Due to the high kinetic energy, of bullets and explosive gun particles, their paths through the abdomen (permanent cavity effect), and the blast effect (temporary cavity effect), firearm injuries (FAI) can produce damage not only in the organ they enter, but in the surrounding tissues as well. Since they change route after entering the body they may cause organ damage in locations other than those at the path of entry. For example, as a result of the crushing onto bone tissues, bullet particles or broken bone fragments may cause further damage outside of the path of travel, For these reasons it is very difficult to predict the possible complications from the size of the actual injury in patients with penetrating abdominal firearm injuries. The factors affecting the mortality and morbidity from firearm injuries have been evaluated in various studies. Insufficient blood transfusion, long duration of time until presenting to a hospital and the presence of colon injuries are common factors that cause the high complication rates and mortality. A total of 120 cases injured in the civil war at Turkey's southern neighbouring countries were admitted to our hospital and evaluated in terms of: development of complications and factors affecting mortality; age, gender, time of presentation to the hospital, number of injured organs, the type of injuring weapon, the entrance site of the bullet, the presence of accompanying chest trauma, the amount of administered blood, the penetrating abdominal trauma index (PATI) and the injury severity score (ISS) scores were determined and evaluated retrospectively. The most significant factors for the development of complications and mortality include: accompanying clinical shock, high number of injured organs, numerous blood transfusions administered and accompanying thoracic trauma. It has also been observed that the PATI and ISS scoring systems can be used in predicting the complication and mortality rates in firearm injuries. Consequently, reducing the mortality and complication rates from firearm injuries is still a serious problem. Despite all of these efforts, there is still a need to determine the optimum treatment strategy to achieve this end goal. PMID- 26131220 TI - Serum iron and A(2)DS(2) score in stroke-associated pneumonia. AB - To evaluate the efficacy of serum biomarkers such as iron, procalcitonin (PCT), C reactive protein (CRP) and A(2)DS(2) scores at hospital admission to predict the onset and severity of stroke-associated pneumonia (SAP), 101 patients with acute stroke were selected and divided into the control and SAP group. Compared with control group, no significant differences were discovered in age, sex, vascular risk factors including hypertension, diabetes and hyperlipidemia, chronic lung disease of SAP group, while a significantly higher level was found in incidence of dysphagia, NIHSS score, A(2)DS(2) score, CURB-65 score, serum iron, serum ferritin, PCT and CRP (P < 0.01). The receiver operating characteristic curve showed that serum iron, serum ferritin, PCT, CRP, A(2)DS(2) score and CURB-65 score had relatively high values in the SAP prediction (all P < 0.01, all AUC > 0.5). When combined ferritin, PCT, and A(2)DS(2) scores and other indicators with CRP for SAP prediction, the model had a larger area under the curve (AUC) and higher specificity than individual prediction models. Spearman regression analysis presented that serum iron, serum ferritin and A(2)DS(2) score were highly correlated with CURB-65 score (P < 0.01). It was suggested that Serum iron and A(2)DS(2) score measured at admission were effective indicators in SAP prediction which could be used for SAP screening and severity prediction. Besides, the specificity in SAP prediction could be improved when Serum iron and A(2)DS(2) score combined with CRP. PMID- 26131221 TI - Role of clinical nursing path combined with traditional Chinese dialectical nursing in the treatment of knee osteoarthritis. AB - OBJECTIVE: To investigate the effect of clinical nursing path in combination with Chinese dialectical nursing on patients with knee osteoarthritis. METHODS: Randomized controlled trial of 60 patients with knee osteoarthritis in our hospital between 2012 and 2013 was enrolled. The control group received only routine care by using traditional model, while the experimental group was subjected to routine care with additional Chinese dialectical nursing. RESULTS: No significant difference in WOMAC scores in the two groups after admission (P>0.05). The WOMAC scores were significantly improved in the experimental group 3 weeks after admission (P<0.05). The mastery of disease and self health care knowledge, compliance with the doctor, nursing satisfaction index and the standard rate of health education in intervention group are obviously better than the control group, the difference was statistically significant (P<0.05). Following-up study indicates that the WOMAC scores and readmission rate was significantly decreased in the intervention group (P<0.05). CONCLUSION: Combination of clinical nursing path with Chinese dialectical nursing can significantly improve the clinical presentation, self-care consciousness and the clinical nursing satisfaction, and it is worthy of clinical application. PMID- 26131222 TI - Impact of oxygen concentrations on fertilization, cleavage, implantation, and pregnancy rates of in vitro generated human embryos. AB - The aim of the present study was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryos on fertilization, cleavage, implantation, pregnancy, multiple gestation and abortion rates. Women 20-48 years old presenting for infertility treatment and accounting for 3484 in vitro fertilization/intracytoplasmic sperm injection cycles were included in the study. Oocytes/embryos were randomly allocated to be incubated under three different oxygen tension environments: (1) 20% O2 in air; (2) initially 20% O2 in air, followed on day 2 (2-4 cells stage) by 5% CO2, 5% O2 and 90% N2; and (3) 5% CO2, 5% O2 and 90% N2 throughout. Interestingly, IVF-derived embryos cultured in 5% O2 yielded higher rates of fertilization and implantation as compared to those incubated in 20% O2 (P < 0.05). Conversely, embryos in 20% O2 yielded higher rates of fertilization, high quality embryo and implantation than those in the 20%-5% O2 group (P < 0.05). Moreover, ICSI-derived embryos cultured in 20% O2 resulted in lower rates of cleavage as compared to those from the 20%-5% O2 group (P < 0.05). These results are consistent with in vitro and subsequent in vivo embryo development being more susceptible to O2 tension fluctuations rather than the degree of O2 tension itself during culture. PMID- 26131223 TI - Toll-like receptor 4 gene polymorphism is associated with chronic periodontitis. AB - Toll-like receptors (TLRs) contribute to the immune response by recognizing patterns presented by bacteria and other pathogens. These receptors have been implicated in the inflammatory response that contributes to gingivitis and periodontitis. Conflicting reports have suggested that variations in the genes encoding TLRs, particularly TLR2 and TLR4, may influence susceptibility to periodontitis. In this study, the contribution of variations in the genes encoding TLR2 and TLR4 in the context of periodontitis was examined in 254 patients with moderate periodontitis, 418 patients with severe periodontitis, and 260 healthy controls free of gum disease. Genomic DNA was extracted from participants' whole blood, and genotyping of TLR2/TLR4 as performed using real time polymerase chain reaction with TaqMan MGB primer. The genotype, allele, and haplotype frequencies were compared among control, moderate periodontitis, and severe periodontitis groups. Statistical analysis was performed using chi-square and logistic regression analyses. Of the 9 polymorphic loci detected in the two genes, one, rs11536889 (G>C) in TLR4, displayed a statistically significant difference in distribution between individuals with moderate periodontitis and severe periodontitis (P<0.05). The distribution of the GG genotype in moderate periodontitis was higher than in the severe periodontitis group (P<0.05). Further, for the haplotype rs7873784, rs1927907, and rs1153688 of TLR4, the distribution of haplotype GCG was statistically different between moderate periodontitis and severe periodontitis (P<0.05, OR=1.501). These findings indicate that variation in TLR4 may affect chronic periodontitis susceptibility in a Han Chinese population. PMID- 26131224 TI - Peptic ulcer hemorrhage combined with acute gout: analyses of treatment in 136 cases. AB - This study aims to compare the safety and curative effect of celecoxib and small dose methylprednisolone sodium succinate in patients with peptic ulcer hemorrhage combined with acute gout. In this randomized, controlled trial, a total of 136 patients with peptic ulcer hemorrhage combined with acute gout were divided into the celecoxib group or the small-dose methylprednisolone sodium succinate group. These patients underwent gastroscopy hemostasis and proton pump inhibitor (PPI) therapy. Moreover, for the treatment of gout, the patients were administered either celecoxib or small-dose methylprednisolone sodium succinate. Adverse reactions and the visual analogue scale (VAS) score were recorded for the two groups. The difference in adverse reactions between the two groups was not significant (chi(2) = 0.002, P = 0.967). The duration of evident pain relief after the first dose of treatment showed a significant difference between the two groups (t = 13.728, P < 0.01). The VAS scores before treatment were not significantly different between the two groups (t = -1.786, P = 0.076). The VAS scores at 6 h, 2 days, 4 days, 6 days, and 8 days after treatment were significantly different between the two groups (t = 3.239, 6.586, 6.280, 3.737, 3.215; P = 0.002, 0.000, 0.000, 0.000, 0.002, respectively). In cases that receive effective gastroscopy hemostasis and PPI therapy, small-dose methylprednisolone sodium succinate exhibits a greater clinical curative effect for peptic ulcer hemorrhage combined with acute gout as compared to celecoxib, and is associated with greater safety. PMID- 26131225 TI - Comparison of two different sevoflurane expelling methods on emergence agitation in infants following sevoflurane anesthesia. AB - PURPOSE: To investigate the effects of two different inhalation anesthetic expelling methods on emergence agitation in infants following sevoflurane anesthesia. METHODS: 100 infants (1~3 years old) with cleft lip and palate and ASA classification I~II were randomized into two groups, a sevoflurane concentration decreasing expelling group (group n = 50 cases) and a low fresh gas flow expelling group (group D = 50 cases). The operation for cleft lip and palate repair was under general anesthesia, in which 30 minutes after initiation of narcosis ending extubation was indicated and after the tubes were removed the patients were sent to the post-anesthesia care unit (PACU) to record anesthesia times, emergence agitation scores, Ramsay scores and adverse reactions including drowsiness, respiratory depression, nausea and vomiting, chills, hiccough or laryngospasms. RESULTS: There were no differences in anesthesia times, awaking time and time until extubation between the two groups. 10 min after start of expelling sevoflurane, blood pressure and heart rates were higher in group N than in group D (P < 0.05). The postoperative agitation incidence and the degree of agitation were lower in group D than in group N (P < 0.05). CONCLUSION: Postoperative agitation is prone to occur in patients with sevoflurane concentration decreasing expelling. Avoiding sevoflurane application maintenance in the stage of sevoflurane expelling reduces the occurrence of postoperative agitation and diminishes physiological and psychological harm. PMID- 26131226 TI - Impact of hepatitis B virus carrier serostatus on neonatal outcomes after IVF-ET. AB - An increasing number of infertile, hepatitis B virus-infected individuals have opted for assisted reproductive technology. However, the impact of the hepatitis B virus carrier serostatus on neonatal outcomes has not been evaluated. Data from 504 patients who delivered singletons were analyzed. In females, hepatitis B surface antigen, hepatitis B e antigen, and antibody to hepatitis core antigen seropositivity significantly decreased the gestational age at delivery. In contrast, the male hepatitis B virus serostatus did not affect the gestational age at delivery. Multiple linear regression analysis showed that maternal weight, gestational age at delivery, and infant gender were significantly related to birth weight. The present retrospective study showed that in females, hepatitis B surface antigen, hepatitis B e antigen, and antibody to hepatitis core antigen seropositivity was significantly associated with the gestational age at delivery after in vitro fertilization-embryo transfer (IVF-ET). PMID- 26131227 TI - The clinical management and outcome of term premature rupture of membrane in East China: results from a retrospective multicenter study. AB - In this study, we investigated the management of term premature rupture of membranes (PROM) and maternal-fetal outcomes in East China. Between January and December 2012, the term delivery data for 111390 pregnant women was retrospectively analyzed. The subjects were divided into two groups: those women who had term PROM (PROM Group, n=13927) and those who did not (Control Group, n=94341). The general patient characteristics, the mode of delivery, and the maternal and fetal complications were recorded. Statistical analysis was completed using the Student's t-test and chi(2)-test. The incidence of term PROM in East China is approximately 12.5%. The maternal demographic and obstetric characteristics were similar between the two groups. Patients in the PROM group had a higher incidence of bacterial vaginitis (BV), chlamydia trachomatis (CT) infection, postpartum hemorrhage, and cesarean section deliveries. Infants in the PROM group experienced higher rates of infection, asphyxia, and jaundice. There was a high cesarean section rate, and further efforts are needed to increase the vaginal delivery rate for women with term PROM. PMID- 26131228 TI - Risk factors of recurrent aphthous ulceration among university students. AB - Recurrent aphthous ulceration (RAU) is a common oral mucosal disease. The etiological involves in genetics, vitamin deficiencies, trauma, immune dysfunction and stress. This study was to explore the related risk factors of recurrent aphthous ulceration (RAU) among college students, and provide basis for further research. We conducted a questionnaire survey among students from three colleges in Wuhu by stratified cluster sampling. The information collected includes general demographic characteristics, dietary habits and so on. The overall prevalence of RAU is 23.30% among college students (23.23% in male and 23.39% in female). There are statistical significance in prevalence of RAU between subjects with RAU and without RAU (P<0.05) the prevalence of RAU in different grade, age, adequate brushing time, good brushing habits, wear dentures or braces, other oral disease, eat barbecue, adequate exercise time is statistic difference. According to the result of multinomial logistic regression analysis, the risk of recurrent aphthous ulceration factors including grade, inadequate brushing time. Tempering was a protective factor of RAU. Some measure should be taken to control dental ulcer, which consist of promoting a correct way of living habits, paying attention to the health conscious diet, strengthen physical exercise, self-decompression and keeping good mentality. PMID- 26131229 TI - Association of vitamin d receptor-a gene polymorphisms with coronary heart disease in Han Chinese. AB - OBJECTIVE: To assess the association between coronary heart disease (CHD) and vitamin D receptor (VDR) gene polymorphisms in Han Chinese adults. METHODS: A total of 215 CHD patients and 67 controls were recruited. In both groups, the VDR gene single nucleotide polymorphisms (SNP) of Tru9I (rs757343), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) were detected, and the frequencies of VDR genotypes were compared between patients and controls. The relationship between VDR FokI genotype and risk for CHD was assessed by logistic regression analysis after adjusting for age and sex. In addition, the clinical parameters and biochemical characteristics of CHD subgroups were compared according to the VDR FokI polymorphism. RESULTS: The frequencies of FokI genotypes in CHD patients were 23.7% for AA, 47.9% for AG, and 28.4% for GG. The frequency of FokI-GG genotype significantly decreased in CHD patients as compared to control group (P = 0.039). No significant differences were observed in other VDR SNPs (rs7975232, rs731236 and rs757343) (P > 0.05) between groups. FokI-A allele carriers had a 2.61-fold increase in the odds (95% CI: 1.116-6.102, P = 0.027) as compare to CHD subjects with FokI mutation. In CHD subgroup, patients with GG genotype had a significantly higher concentration of high-density lipoprotein cholesterol than those with AG genotype or A* genotype (P = 0.001, respectively). CONCLUSION: VDR FokI polymorphisms appear to be associated with CHD. GG genotype predicts a higher HDL-cholesterol in CHD adults. PMID- 26131230 TI - Effect of hepatitis C virus infection on the outcomes of in vitro fertilization. AB - OBJECTIVE: To investigate the impact of Hepatitis C Virus (HCV) infection on in vitro fertilization (IVF) outcomes. METHODS: A retrospective analysis was conducted using IVF cases occurring at the Centre for Reproductive Medicine, General Hospital of Tianjin Medical University between January 2008 and December 2013. A total of 1424 couples undergoing IVF cycles were included: Ninety couples where the female was HCV positive, 78 couples where the male was HCV positive, and 1256 control couples where both the male and female were HCV negative by for the presence of HCV RNA and antibodies. RESULTS: All experimental and control groups (HCV-positive men, HCV-positive women, and controls) had similar sperm parameters, ovarian stimulation, fertilization and pregnancy results. CONCLUSION: HCV infection has no affection on IVF treatment outcomes. PMID- 26131231 TI - Dipeptidyl peptidase 4 concentration influenced by serum insulin levels rather than arterial stiffness index in type 2 diabetics. AB - OBJECTIVE: To investigate whether inhibitors of dipeptidyl peptidase-4 (DPP-4) can suppress the atherosclerotic development in diabetic patients. METHODS: The prospective study was carried out in the Out-patient Department of XuHui Central Hospital, Shanghai, China, between March and August 2013. The correlation of major index of glucose and lipid metabolism profiles, and the arterial stiffness index (AI) between diabetic patients and healthy subjects were analyzed. PATIENTS OR MATERIALS: 39 patients with type 2 diabetes and 29 healthy subjects were enrolled for measurements of blood glucose, plasma insulin, HbA1c, TC, cholesterol, HDL, AI and body mass index (BMI). RESULTS: Significant differences were found between DPP-4 and blood glucose (fasting and 2 h postprandial), HbA1c, cholesterol, high density lipoprotein and arterial stiffness in normal subjects and diabetic patients. Only the fasting insulin concentration and high density lipoprotein had a significant impact on DPP-4 levels. CONCLUSIONS: It was clear that insulin (fasting) and HDL levels had an impact on DPP-4 activity but only in patients with Type 2 diabetes. The arterial stiffness index was not correlated with DPP-4 levels in Type 2 diabetic patients. PMID- 26131232 TI - Randomized study of gefitinib versus pemetrexed as maintenance treatment in patients with advanced glandular non-small cell lung cancer. AB - Gefitinib was compared with pemetrexed as maintenance therapy in Patients with Advanced Glandular Non-small Cell Lung Cancer, mainly regarding clinical effect and side effect. A randomized trial of pemetrexed as study group (500 mg/m(2), dl) versus gefitinib as the control group [250 mg on night 1, 250 mg on morning 2 (every day)] was conducted in 188 patients, 94 cases in each group with a therapy cycle of 21 days. In addition, the study group was also treated with folic acid, vitB12 and dexamethasone. Therapeutic effects and adverse reactions of the two groups were compared. Patients of two groups completed four cycles of chemotherapy mostly, and there was no complete remission (CR) case. The median cycle of chemotherapy was 2 for the study group, and partial response (PR), stable disease (SD), progressive disease (PD) were observed in 28 (29.8%), 34 (36.2%), 32 (34.0%) cases respectively. The median-cycle was 3 for the control group, PR, SD and PD were observed in 17 (18.1%), 23 (24.5%), 54 (57.4%) cases respectively. The effective rates were 29.8% and 18.1% for pemetrexed (28 cases) and gefitinib (17 cases) respectively (P > 0.05). However, there was a statistically significant difference in disease control rates between the 2 groups (65.0% vs 42.6%; P < 0.05). Adverse reactions occurred in two groups were mainly mild adverse reactions of 1-2 degree, without renal failure. The study group and control group had three and five cases of mild infection respectively, without statistically significant difference. There was no significant difference in the incidence rate of rash and alopecia between the two groups (P > 0.05). However, the number of cases with neutropenia, anemia, thrombocytopenia, gastrointestinal reactions and fatigue in the study group was lower than that of the control group, with a statistically significant difference (P < 0.05). Considering the disease control rate and the tolerance of patients with advanced NSCLC, pemetrexed is strongly recommended to be used in clinical. PMID- 26131233 TI - Patients with polycystic ovary syndrome have successful embryo arrest. AB - In this retrospective study, we investigate the relationship between embryo arrest and polycystic ovary syndrome (PCOS) during in vitro fertilization-embryo transfer (IVF-ET). In this study, 667 subjects were enrolled, including 330 patients with PCOS and 337 subjects without PCOS. The subjects underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles at the Reproductive Medical Centre of Henan Provincial Hospital from January 2009 to December 2012. Four protocols were used to stimulate the ovaries, including long protocol, super-long down-regulation protocol, short protocol and antagonist protocol. Oocytes were retrieved using transvaginal ultrasound guidance. Pronuclei were checked on the next morning after IVF/ICSI. Cleavage stage embryo was assessed after 62-66 hours. Women with PCOS had significantly elevated body mass index, basal luteinizing hormone, estradiol and testosterone compared with normal women. Basal Follicle stimulating hormone level in PCOS patients was lower compared with that in control group. After IVF-ET, PCOS patients had more available oocytes than subjects in control group. PCOS patients had slightly lower fertilization rate than the controls in IVF cycles, but in ICSI cycles, fertilization rate in PCOS patients was significantly higher than that in controls. For either IVF or ICSI, the embryo arrest rate was not changed by PCOS. Moreover, there was no significant difference in embryo arrest rate between both groups adopting different stimulation protocols. Interestingly, embryo arrest rate was not correlated with testosterone for patients in PCOS group. The data indicated that patients with PCOS had successful early embryo arrest during IVF-ET. PMID- 26131234 TI - Association of interleukin-6 polymorphisms with susceptibility to hepatocellular carcinoma. AB - TARGET: Our study was to investigate the effects of interleukin-6 (IL-6) polymorphisms (rs2069837 and rs17147230) on the risk for hepatocellular carcinoma (HCC). METHODS: A total of 226 HCC cases and 220 healthy controls were admitted into the study and genomic DNA was extracted from the peripheral blood. The genotyping was conducted by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the relationship of IL-6 rs2069837 and rs17147230 polymorphisms with HCC susceptibility. RESULTS: The frequency of GG genotype of rs2069837 was higher in HCC patients, compared with controls (P < 0.05). Moreover, the results indicated that GG genotype was related with increased risk for HCC (OR = 2.303, 95% CI = 1.056-5.025). Similarly, the risk for G allele carriers was higher than that of A allele (OR = 1.392, 95% CI = 1.046-1.852). For rs17147230, TT genotype showed strong effect on HCC susceptibility (OR = 2.089, 95% CI = 1.135-3.845) and T allele appeared to be a risk factor for HCC (OR = 1.326, 95% CI = 1.010-1.740). Further analysis showed that G-T haplotype was associated with increased risk for HCC (OR = 3.125, 95% CI = 1.845-5.294, P = 0.000). CONCLUSION: IL-6 rs2069837 as well as rs17147230 were associated with HCC susceptibility. In addition, G-T haplotype also served as a genetic-susceptibility factor for HCC. PMID- 26131235 TI - Visfatin and ghrelin: can they be forthcoming biomarkers or new drug targets for asthma? AB - BACKGROUND & AIM: Asthma represents chronic inflammation of the airways and is associated with bronchial hyperresponsiveness and reversible airway obstruction. A novel adipokine visfatin and an appetite-modulating hormone ghrelin play a role in several diseases related with inflammation. Although visfatin is a pro inflammatory adipokine, ghrelin mainly exerts anti-inflammatory effects. However, very little is known about the role of visfatin and ghrelin in asthma. In the present study, we aimed to investigate the role of visfatin and ghrelin in asthma by evaluating their serum levels in asthmatic patients. MATERIALS AND METHODS: This study was performed on 27 asthma and 23 healthy controls. Blood samples were collected in tubes without EDTA. Serum levels of visfatin and ghrelin were measured by human ELISA assay kits. Statistical analyses were performed by SPSS 16.0 package program and differences were considered statistically significant at p < 0.05. RESULTS: Serum levels of visfatin and ghrelin were significantly higher in asthma group (respectively; p = 0.001, p = 0.002). CONCLUSION: While visfatin has a pro-inflammatory role, ghrelin exerts an anti-inflammatory effect in asthma. Therefore, visfatin can be a forthcoming biomarker and ghrelin may be a new anti-inflammatory drug target to diagnose and treat asthmatic patients. PMID- 26131236 TI - Relationship between IL-27 gene polymorphism and susceptibility of rheumatoid arthritis in Chinese Han population. AB - OBJECTIVE: To investigate the relationship between IL-27 gene polymorphism and the susceptibility of rheumatoid arthritis (RA) in a Chinese Hans population. METHODS: 310 RA patients and 310 healthy controls were examined in this study. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique was used in the detection of the genotype in three loci of IL-27 gene ( 964A/G, 2905T/G, and 4730T/C). We compared genotype and allele frequency and distribution of these two groups. RESULTS: The genotype distribution of the case group and the control group were all in accordance with Hardy-Weinberg equilibrium (P>0.05). The difference of genotype and allele frequencies of three loci between these two groups showed no statistically significant (P>0.05). But the frequencies of G-T-C haplotype was significantly higher in the case group than in the control group, the difference showed statistically significant (OR=2.001, 95% CI: 1.121~3.573; P=0.0170). G-T-T haplotype in case group was significantly lower than that in the control group, the difference showed statistically significant (OR=0.715, 95% CI: 0.527~0.970, P=0.030). CONCLUSION: In Chinese Hans population, IL-27 gene haplotypes were correlated with the risk of RA. G-T-C haplotype was the risk factors for the incidence of RA, but G-T-T haplotype maybe was the protective factor of RA. PMID- 26131237 TI - Comparison of early postoperative period electrophysiological and clinical findings following carpal tunnel syndrome: is EMG necessary? AB - In this study, we aimed to compare the clinical findings and ENMG results of the patients who underwent surgery due to CTS, in the preoperative and early postoperative period. METHODS: 33 wrists of 29 patients who underwent open carpal tunnel surgery in our clinic due to CTS, between 2009 and 2011, were evaluated. Electrophysiological progress was evaluated with ENMG and clinical state with Boston scale. RESULTS: A significant decrease was observed in the postoperative BS symptomatic (SSS) and functional (FSS) scores of patients as compared to preoperative period (P=0.00). In the electrophysiological findings, statistically significant improvement was observed in all groups but very severe CTS group (P<0.05). When preoperative and postoperative EMG findings were compared, changes in DSL and DSA values were statistically significant (P<0.05). However, no statistically significant difference was seen between DML (P=0.085) and DMA (P=246) values on the 3rd month. When an examination was conducted on the patients whose DML and DSL values could not be obtained in the preoperative EMG, DML values were obtained in the early postoperative period in 6 of 7 cases (85.71%, P<0.001), and DSL values were obtained in 17 of 24 cases (70.8%, P<0.000). CONCLUSIONS: Sensory nerve findings were more significant, showed faster recovery compared to motor nerve findings, and accompanied the clinical recovery. Performance of an EMG test, especially on sensory nerves, will be more effective in patients selected in the early period, with the exception of patients with very severe CTS. PMID- 26131238 TI - Comparison of maternal and fetal outcomes of IVF and spontaneously conceived twin pregnancies: three year experience of a tertiary hospital. AB - OBJECTIVES: The aim of this study was to compare maternal and fetal outcomes of spontaneously conceived and in-vitro fertilization (IVF) twin pregnancies that were admitted to our obstetric clinic and delivered between January 1, 2011 to November 1, 2014. MATERIAL METHOD: A total of 84 twin pregnancies were enrolled for the study and divided into two groups: group 1 as IVF (n = 19) and group 2 as spontaneously conceived (n = 65) twin pregnancies. Data of neonatal various morbidities needs neonatal intensive care unit (NICU) such as necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), sepsis, retinopathy of prematurity (ROP), and intraventricular hemorrhage (IVH) and maternal morbidities such as preeclampsia, eclampsia, postpartum bleeding, gestational diabetes mellitus(GDM) were collected by hospital records. RESULTS: There were no statistical difference between two groups regarding hypertension related to pregnancy, intrauterine growth retardation, Apgar scores, NICU needs, birth weight and height (P > 0.05). The rate of premature rupture of membranes, maternal age, antenatal anemia and premature birth were detected higher in IVF group when compared with the other group (P < 0.05). CONCLUSION: Although twin pregnancies, regardless of conception method are high risk pregnancies in terms of obstetric and perinatal outcomes, premature rupture of membranes, maternal age, antenatal anemia and premature birth risks are higher in IVF twin pregnancies. PMID- 26131239 TI - A hidden reason for menopausal symptoms in premenopausal aged women: depression. AB - BACKGROUND: The relationship between depression and reproductive hormone changes in menopausal women is well konown but recent animal studies showed that depression can also cause changes in reproductive hormone levels. According to this, we aimed to eveluate the impact of depression on circulating follicle stimulating hormone and estradiol levels in premenopausal women in terms of menopausal symptoms. MATERIAL-METHOD: A total of 120 premenoupausal women (age ranges 41-45) were divided into two groups as: study group consisted of patients (n = 60) with depression and the control group (n = 60) involved healthy women. Psychometric assessment of study group was done by the Turkish version of Structured Clinical Interview for DSM-IV Diagnosis.The presence of menopausal symptoms of all subjects was assessed by the Turkish version of Menopause Rating Scale and hormonal activity by estimating estradiol and follicle-stimulating hormone levels. RESULTS: Study group had significantly lower mean concentration of estradiol and higher intensity of menopausal symptoms than control group. Presence and severity of menopausal symptoms were not associated with follicle stimulating hormone concentrations. CONCLUSION: The results of this study confirm the connection between menopausal symptoms and depression both on clinical and physiological level.The current study is unique in its ability to assess the effects of depression on menopausal symptoms in women as they are still reproductive. PMID- 26131240 TI - Prostate calculi can higher urinary retention probability and worsen uncomfortable feeling after prostate biopsy but not predict cancer. AB - To investigate whether prostatic calculi might influence the urinary retention (UR) probability, the quality of life (QOL) and the positive rate of cancer after prostate biopsy in middle-aged and old male with PSA higher than normal. This study comprised a retrospective analysis of data from 685 patients (prostatic calculi group 325 VS non-prostatic calculi group 360), those who had undergone transrectal ultrasound-guided prostate needle biopsy (TRUS PNB) from Sept. 2012 to Sept. 2014. To these people, prostate volumes (PV) were recorded by TRUS and prostatic calculi were defined as present or absent. Other variables such as age, International Prostate Symptoms Score (IPSS), the quality of life (QOL), total PSA (prostate specific antigen) rate, and urinary retention cases were also recorded and compared. Among these patients, 154 (prostatic calculi group 73 VS non-prostatic calculi group 81) were diagnosed with prostate cancer through postoperative pathological, there was no significant difference between the two groups. But compared to the non-prostatic calculi group, after the prostate biopsy, the group with prostatic calculi experienced more uncomfortable feelings and enjoyed higher Urinary retention probability. Prostatic calculi could worsen QOL and higher urinary retention probability after transrectal ultrasound-guided prostate needle biopsy, but it is a weak predictor of positive results of prostate cancer in middle-aged and old male with PSA higher than normal. PMID- 26131241 TI - Correlation between serum cystatin C level and elderly hypertensive patients combined coronary heart disease. AB - OBJECTIVES: To explore the correlation between serum cystatin C level and elderly hypertension with coronary heart disease patients. METHODS: 500 hypertensive patients combined coronary heart disease were selected by coronary angiography. 321 of them were elderly patients with hypertension (male 204, female 117), and 400 of them were elderly patients with coronary heart disease (male 257, female 143), The serum cystatin C level of all patients were detected by immunoturbidimetry, and analyzed the correlation between the serum cystatin C level and different degree of blood pressure and the degree of coronary artery stenosis in elderly patients. RESULTS: The serum cystatin C level was closely related with the blood pressure and the degree of the coronary artery stenosis. The higher the blood pressure level and the more serious the coronary artery stenosis, the higher the serum cystatin C level; The serum cystatin C level of hypertensive patients with coronary heart disease patients (Group D) were markedly higher than the level of the patients without hypertension and coronary heart disease patients (Group A), and the level of the patients with coronary heart disease (Group B) and the hypertension group (Group C) (P < 0.05). CONCLUSION: The serum cystatin C level of elderly patients with hypertension and coronary heart disease were closely related with the degree of blood pressure and coronary arteries stenosis. The serum cystatin C maybe a predictor of disease severity in elderly hypertensive patients with coronary heart disease. PMID- 26131242 TI - Correlation of serum uric acid with bone mineral density and fragility fracture in patients with primary osteoporosis: a single-center retrospective study of 253 cases. AB - OBJECTIVE: This study aimed to investigate the correlation of serum uric acid with bone mineral density (BMD) and fragility fracture in primary osteoporosis (PO) patients. METHODS: A retrospective analysis of biochemical parameters including bone turnover markers and bone density was done in patients (n=253) received initial treatment for PO from January 2011 to May 2012 at the Shanghai First People's Hospital. RESULTS: Pearson correlation analysis and multiple regression analysis showed that serum uric acid positively correlated with the lumbar spine BMD (P<0.05); serum uric acid negatively correlated with urine calcium/creatinine ratio, but positively correlated with blood 25-hydroxyvitamin D (25 [OH] D) (P<0.05); the serum uric acid in postmenopausal women with the history of fragility fracture was significantly lower than that in women without the this disease history. CONCLUSION: Serum uric acid may be a protective factor of bone metabolism in primary osteoporosis patients. PMID- 26131243 TI - Biliary tract and pancreatic surgery complicated by acute pancreatitis: a clinical analysis. AB - OBJECTIVE: To study the clinical treatment features of biliary tract and pancreatic surgery complicated by acute pancreatitis. METHODS: A retrospective analysis of 21 cases of biliary tract and pancreatic surgery complicated by acute pancreatitis in the Department of General Surgery in our hospital during May 2005 to July 2011 was performed; the clinical treatment features were analyzed in terms of surgical option, onset interval of acute pancreatitis after last surgery, length of stay in hospital and Ranson score. RESULTS: There was no statistic difference between the two groups (A: The onset interval of acute pancreatitis after last surgery < 0.5 year. B: The onset interval of acute pancreatitis after last surgery > 0.5 year) in pathogenetic condition and length of stay in hospital. All patients were discharged after treatment, a follow-up of 6-18 months found no recurrence of pancreatitis. CONCLUSION: There is no relevance between the treatment feature and onset interval of biliary and pancreatic surgery complicated by acute pancreatitis. The disease is still treated meanly with symptomatic and supportive treatment, while the etiological treatment is also particularly important. PMID- 26131244 TI - Short versus long intramedullary nails for the treatment of intertrochanteric hip fractures in patients older than 65 years. AB - OBJECTIVE: The purpose of this study was to compare failure rates between short and long intramedullary nails used for the treatment of intertrochanteric hip fractures in patients over 65 years of age. METHODS: A retrospective review of 156 patients aged more than 65 years with femoral intertrochanteric fractures from December 2010 to December 2012 was performed. The patients were allocated to two groups: those treated with long nail (n=59) and short nail (n=97). Relevant patient variables and medical comorbidities were collected. Medical comorbidities were evaluated according to the American Society of Anesthesiologists classification and medical records were also reviewed for age, sex, intraoperative blood loss, operative time, length of stay, time to fracture union, hip pain, Harris Hip Score 1 year postoperatively, and failure rates. The failure rate was defined as periprosthetic fracture or reoperation requiring removal or revision of nail. Variables were statistically compared between the two groups, with statistical significance at P<0.05. RESULTS: Patients treat with long nails and short nails were comparable for all assessed clinical variables (P>0.05). There were no statistically significant differences between these groups in intraoperative blood loss, time to fracture union and Harris Hip Score at 1 year postoperatively (P>0.05). The long nail group had significantly less failure rate (0/59) and hip pain rate (3/59) than those with short nail (3/97 and 13/97, respectively) (P < 0.05), but the operative time was significantly longer in the former (60.60 +/- 11.43 minutes) than the latter (53.10 +/- 8.51 minutes) group (P < 0.05). CONCLUSIONS: Both the long and short intramedullary nails are the optional internal fixation choices for femoral intertrochanteric fracture in the aged patients older than 65 years. But the long nail could avoid the refracture of femur and reduced postoperative hip pain. PMID- 26131245 TI - Stress fracture of the distal fibula in flatfoot patients: case report. AB - The increase in proportional loading of the fibula with progression of hindfoot deformity would lead to high fibular loads during rapid walking, resulting in insufficiency fractures. We report an unusual mechanism of such fracture in a textile worker resulting from valgus alignment from a stage III flatfoot deformity. The stress fracture was missed initially and only confirmed by CT examination. The patient responded well to nonoperative treatment and had an excellent recovery with no residual symptoms finally. Fracture of the distal fibula caused by rigid hindfoot valgus in stage III flatfoot deformity is a previously undescribed injury. We report a patient who presented with this injury, the possible mechanisms of such injury, its management and outcome. PMID- 26131246 TI - A mass seen under gastroscopy "disappeared" during laparotomy. AB - We describe here a case of 36-year-old man with a hepatic cavernous hemangioma that was misdiagnosed as a gastric submucosal tumor (SMT) with endoscopic ultrasound (EUS) and CT scan. On gastroscopy, a submucosal tumor was found on the cardia of the stomach. Based on EUS and abdominal CT scan, the lesion was diagnosed as a gastric duplication cyst. The patient underwent gastroscopy after receiving laparotomy at the median point of the abdomen. A spherical mass arising from the left triangular ligament of the liver region was found. There was no abnormal finding at the cardia of the stomach. PMID- 26131247 TI - Delayed presentation of uterine perforation with ovary migration after dilatation and curettage. AB - We present a rare but serious uterine perforation. A 31-year-old woman was referred to our department for hyperechogenic mass in uterus on ultrasonography after Dilation and curettage (D&C) for the adherent placenta and retained products of conception. Transvaginal ultrasound examination showed that a mass with several follicles measuring 35*29 mm was seen emanating from the right posterior wall of the uterine cavity, and there was absence of the myometrial tissue. A hysteroscopy and laparoscopy showed a uterine perforation with ovary incarceration. The ovary was rehabilitated, and the uterine perforation site was incised. D&C can not be performed when delayed presentation of uterine perforation with migration of an extrauterine organ is suspected, particularly, some of them are asymptomatic after a difficult intrauterine operation. PMID- 26131248 TI - Simultaneous idiopathic segmental infarction of the great omentum with spontaneous splenic rupture: a rare association. AB - Idiopathic segmental infraction of the greater omentum (ISIGO) is a rare cause of acute abdomen. One of the main symptoms is right-side abdominal pain, while its etiology is still unclear. Until now, ISIGO simultaneously with spontaneous splenic rupture (SSR) has not been reported. Here, we presented a case of a 35 year old man, who was admitted with an acute abdomen, and the clinical diagnosis was ISIGO with SSR. He had a significant previous medical history of the vein thrombosis of lower limbs. Partial omental resection and splenectomy were performed, and the postoperative recovery of the patient was excellent. We also highlighted several possible theories to explain the etiology of the ISIGO, and emphasized that surgical methods, including laparoscopic surgery and laparotomy, are still the best way to treat the ISIGO at the emergency condition. PMID- 26131249 TI - Laparoscopic hysterectomy of large uteri using three-trocar technique. AB - AIM: The uterus with its size exceeds 12 weeks of gestation have been considered a relative contraindication to laparoscopic hysterectomy. With surgical techniques progressed and laparoscopic instruments improved, laparoscopic hysterectomy for large uteri have been performed safely and effectively. The aim of this study is to assess the feasibility and safety of laparoscopic hysterectomy on uterus more than 800 g using a three-trocar technique on 18 patients. METHODS: From June 2011 to June 2013 a total of 18 consecutive patients underwent laparoscopic hysterectomy for benign gynaecological conditions. All of the 18 consecutive cases were successfully completed by laparoscopy with the instruction of the procedure. RESULTS: All of the 18 cases were completed by laparoscopy without major complication. The average time of the surgery was 107 min (65-180), the average blood lost was 225 ml (50-800 ml), the average weight of the uterus was 1105 g (820-1880 g), and the average HGB drop was 0.9 g/dl (0.2 1.9 g/dl). CONCLUSION: Based on appropriate techniques and careful operate, Laparoscopic hysterectomies for large uteri using three-trocar is safe and feasible to most of the patients. PMID- 26131250 TI - Comminuted radial head fractures treated by the Acumed anatomic radial head system. AB - OBJECTIVE: The treatment of comminuted radial head fractures is still challenging. A radial head replacement is more effective in comminuted radial head fractures. The aim of this paper was to present the medium-term results of the Acumed anatomic radial head system (AARHS). METHODS: This study was performed on 12 patients with traumatic elbow fracture and instability between 2008 and 2011 of whom 12 were reviewed at a mean follow-up of 60.8 months (19 to 77 months). The evaluation included a record of pain, function, muscle strength, contracture and rotation. The outcome was assessed using the Hospital for Special Surgery total elbow scoring and a modified Disability of Arm Shoulder Hand (DASH) questionnaire. RESULTS: The average flexion and extension arc was 130 degrees (range, 110 degrees to 140 degrees ). The mean range of elbow supination was 75 degrees (rang, 60 degrees to 85 degrees ) and pronation 80 degrees (range, 65 degrees to 90 degrees ). There were no complications such as infection, implant loosening, instability of the elbow, cubitus valgus, osteoporosis of the capitellum, or pain in the forearm and wrist. The mean DASH score was 11.9/100 (0 to 25/100). CONCLUSION: The radial head replacement with the AARHS can provide effectively stability and good clinic results at the middle term following up. Our experience has encouraged us to continue using the AARHS in comminuted fractures, especially when instability of elbow is a potential problem. PMID- 26131251 TI - Compression of the ostium of left main coronary artery caused by aortic root intramural hematoma after blunt thoracic trauma. AB - We reported a case of compression of the ostium of left main coronary artery caused by aortic root intramural hematoma after blunt thoracic trauma treated with percutaneous coronary intervention (PCI). A 46-year-old man visited our hospital because of exertional chest discomfort and dyspnea for 4 months. He was diagnosed as compression of the ostium of left main coronary artery caused by aortic root intramural hematoma, severe stenosis in the ostium of the left main coronary artery. The percutaneous coronary intervention was conducted, and a drug eluting stent was implanted successfully. The symptoms were improved and the patient had a good recovery after PCI surgery. PMID- 26131252 TI - Retroperitoneal abscess and acute acalculous cholecystitis after iatrogenic colon injury: report of a case. AB - Acute acalculous cholecystitis has a high mortality rate due to the difficulties in early diagnosis and high rate of complications like empyema, gangrene and perforation. We report a case of 20-year-old male with acute severe pancreatitis, acute renal failure and acute peripancreatic fluid collection who was transferred to our department after blood filtration treatment in ICU. After percutaneous catheter drainage for 20 hours, the patient got a high fever. Computed tomography revealed retroperitoneal colon injury. In this case, percutaneous catheter drainage was performed again and the pus cavity was flushed regularly, after which the patient's state gradually improved. Unpredictably, septic shock appeared on the 51(st) day. Repeated computed tomography revealed acute acalculous cholecystitis and abscess formation. After percutaneous transhepatic gallbladder catheterization and drainage, the patient got better gradually. Three months later the retroperitoneal catheter was removed. Four months later, ultrasound examination showed normal gallbladder and the catheter was removed. PMID- 26131253 TI - Cerebellopontine angle empyema after lumbar disc herniation surgery. AB - BACKGROUND: Lumbar discectomy is still one of the most common spinal surgeries performed today. Nevertheless, there are few publications considering severe complications. CASE DESCRIPTION: We report a case with severe complication, without any previous report, a brain empyema after cerebrospinal fluid leak with good outcome afterword. A 45 years old man, returned six days after surgery, presenting cerebrospinal fluid leak, which after clinical and laboratory deterioration was reoperated. In the 14th postoperative facing worsening level of consciousness was diagnosed empyema in cerebellopontine angle and hydrocephalus underwent emergency surgery. Evolved with hemiplegia in the first postoperative attributed to vasculitis, completely recovered after 5 days. CONCLUSIONS: Although infrequent, lumbar discectomy is subject to severe complications, which as the case presented, can be dramatic. In surgeries must be careful to avoid cerebrospinal fluid leak e infectious complications. PMID- 26131254 TI - Hyperreactio luteinalis after delivery: a case report and literature review. AB - Hyperreactio luteinalis (HL), characterized by bilateral functional multicystic ovarian enlargement during pregnancy and puerperium, mostly occurs in third trimester. As a rare benign disease, HL is usually self-limited. However, some cases are dignosed by unnecessary operation. This is a case report of HL appearing a week after delivery. The patient took a puncture biopsy of ovarian tumor guided by ultrasound to rule out of ovarian malignancy. Without any specific treatment, the disease regressed spontaneously. PMID- 26131255 TI - Implantation of metastatic mucinous adenocarcinoma in the hernial sac: a case report. AB - Malignant tumors may appear in inguinal hernias. We report a rare case of a metastatic mucinous adenocarcinoma in the inguinal canal in a patient presenting clinically with an inguinal hernia. The clinical details, histological findings and surgical management were described. PMID- 26131256 TI - Pachymeningitis as a manifestation of ANCA-associated vasculitis: a care report and literature review. AB - Pachymeningitis is a rare cause of headache characterized by dura mater thickening with various origins. We present a 67-year-old male with cranial and spinal pachymeningitis and MPO-ANCA-associated vasculitis, which is considered as the cause of pachymeningitis of this patient. After revision of other 32 reported cases, our study suggested cranial and spinal pachymeningitis could be a manifestation of ANCA-associated vasculitis. Thus, it is important to screen other manifestations of ANCA-associated vasulitis as soon as pachymeningitis was suspected. PMID- 26131257 TI - Negative pressure pulmonary edema after craniotomy through the endonasal transsphenoidal approach. AB - We describe a case of negative pressure pulmonary edema that occurred in the post anesthesia care unit in a patient who had undergone transsphenoidal resection of a pituitary adenoma. Negative pressure pulmonary edema is an uncommon complication of general anesthesia. In this case, the patient's nasal cavity had been filled with surgical packs and she had not become accustomed to breathing through her mouth, in addition to her large tongue and small oropharyngeal cavity, residual effect of anesthetic may resulting in tongue falling which caused airway obstruction. The main causative factor is excessive negative intrathoracic pressure generated by the patient's spontaneous forced inspiration in an effort to overcome the airway obstruction. It typically developed rapidly, and may be life threatening if not diagnosed promptly. After re-intubation for a short period of mechanical ventilation with positive end expiratory pressure (PEEP 10 cm H2O) and a bolus of intravenous furosemide, the patient recovered rapidly and discharged 8 days after surgery. PMID- 26131258 TI - Woman with rectal condyloma acuminatum: a case report. AB - Condyloma acuminatum (CA) is caused by human papilloma virus (HPV) infection, and it often occurs in the genital and perianal regions. The subtypes of HPV mainly include HPV-6, -11, -16, and -18. This case report presents a 37-year-old woman admitted to hospital because of lower abdominal pain and increased stool frequency for > 1 year. Colonoscopy found a neoplasm with a diameter ~5 mm in the rectum, ~5 cm from the anal margin. The pathological diagnosis of the excised specimen was CA. HPV DNA analysis indicated HPV-6. After asking the history closely, the patient admitted that her husband had CA, and they once had anal intercourse. The patient was discharged on the third day after the operation, and she was referred to a dermatology and venereal disease specialist for further treatment. PMID- 26131259 TI - Fatal bacteremia by neisseria cinerea in a woman with myelodysplastic syndrome: a case report. AB - Neisseria cinerea has been rarely found in blood cultures. In this study, we are reporting a case of a Myelodysplastic Syndrome (MDS) patient in whose blood Neisseria cinerea was found and led a fatal consequence. This case will call our attentions to the uncommon pathogens in the pathogenicity of end-stage patients. PMID- 26131260 TI - Airtraq((r)) laryngoscope-assisted fiberoptic bronchoscope intubation in a child with Pierre-Robin sequence: a case report. AB - We present a new strategy method of combining use of Airtraq((r)) and fiberoptic bronchoscope (FOB) for tracheal intubation in 3-year-old child with Pierre-Robin sequence. PMID- 26131261 TI - A case of renal failure developing in association with African mango consumption. AB - Chronic kidney disease continues to represent a significant health problem in all societies. One of the main factors accelerating renal progression is nephrotoxins. The African mango is a plant added to many foods and commonly consumed in West Africa. No toxic effect has to date been shown. Our aim was to discuss the 42-year-old patient who became dialysis-dependent through developing rapid renal progression following 2.5-month African mango use. To the best of our knowledge, our patient is the first case of chronic renal insufficiency developing in association with African mango consumption. PMID- 26131262 TI - Decreased expression of stem cell factor mRNA and protein in the gallbladders of guinea pigs fed on high cholesterol diet. AB - OBJECTIVE: Sufficient evidence suggests that the c-kit protooncogene receptor and its ligand stem cell factor (scf) signal pathway play a crucial role in interstitial cells of Cajal (ICCs) development and maintenance of their phenotype. We aimed to determine the expressions of scf mRNA and scf protein in the gallbladders in guinea pigs fed on high cholesterol diet (HCD). METHODS: The gallbladder and serum samples from 20 guinea pigs of HCD and from 20 guinea pigs of standard diet (StD) were used for this study. Serum lipid analysis was performed using standard laboratory procedure. Expression of scf mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR), and expression of scf protein was detected by Western blot analysis. RESULTS: Laboratory results showed serum total cholesterol (TC), low density lipoprotein (LDL) cholesterol , high density lipoprotein (HDL) cholesterol and triglyceride (TG) concentrations were significantly higher in the HCD group than in the StD group of guinea pigs (P < 0.001, respectively). Decreased expression of scf mRNA and protein were demonstrated in the HCD group compared with the StD group (P < 0.05 respectively). CONCLUSION: The data indicates that the expression of scf mRNA and c-kit protein is significantly decreased in the gallbladders in guinea pigs of HCD. PMID- 26131263 TI - Insulin secretion and tolerance of women with different gestational glucose regulation one year postpartum. AB - Glucose intolerance during pregnancy is defined as gestational diabetes mellitus (GDM). 95 women after 1 year birth were divided into GDM (n = 22), GIGT (gestational impaired glucose tolerance, n = 41) and NGT (normal, n = 32) groups. The GIGT group was subdivided into GIGT1 (abnormal blood glucose in 1 h, n = 11), GIGT2 (in 2 h, n = 18) and GIGT3 (in 3 h, n = 12) after oral glucose tolerance tests (OGTT). Compared with GIGT and NGT groups, GDM group showed higher FBG, 75 g OGTT 2 h BG, HOMA-IR, BMI, TCH, TG and LDL-C levels, while lower IFI. GIGT group had higher 75 g OGTT 2 h BG and BMI than NGT. IFI level was the lowest, while HOMA-IR the highest in GIGT1 subgroup. GDM women are more susceptible to impaired insulin secretion, insulin tolerance and dyslipidemia. Women in GIGT1 subgroup may tend to developing DM. PMID- 26131265 TI - Associations between tumor markers and the risk of colorectal polyp recurrence in Chinese people. AB - Colorectal cancer primarily arises from the polyps of the colon. Early identification of the recurrence of colorectal polyps represents the best opportunity to prevent the occurrence of colorectal cancer. Thus, the high risk of recurrence is the primary problem. The aim of this study was to examine the associations between tumor markers (CEA and CA19-9) and colorectal polyp recurrence in Chinese people. The risk of colorectal polyp recurrence was studied in 156 subjects (113 males and 43 females, 58.654+/-11.447 years old) who underwent colonoscopy and polypectomy for the first time between January 2011 and August 2014 at the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China. All subjects underwent colonoscopies within 6-12 months. Between the colorectal polyp recurrence group and the no recurrence group, the CEA and CA19-9 levels were significantly different, and the trend analyses were consistent with increased risks of recurrence with increasing CEA and CA19-9 levels among the males and patients with single polyps, multiple polyps and proximal colon polyps. The recurrence of colorectal polyps was significantly associated with increased CEA and CA19-9 levels. PMID- 26131264 TI - Simvastatin ameliorates low-dose streptozotocin-induced type 2 diabetic nephropathy in an experimental rat model. AB - The present study aims to study the possible renal protective effect of simvastatin in the development and progression of type 2 diabetic nephropathy. A rat model of T2DN was induced by high-fat diet together with single low-dose of streptozotocin. The diabetic rats were either given treatment or vehicle control for 13 weeks to develop nephropathy. At the end of treatment, parameters of renal function were determined. Kidney samples were collected for histological studies and generated homogenates for biochemical analysis. In T2DN rats, severe hyperglycemia was developed, FBG were markedly elevated. Diabetes induced significant alterations in renal structure, such as severe reduction of glomerular tufts, increase in Bowman's spaces, thickening of GBM. In addition, and SCr, UAER and BUN are elevated, accompanied with reduction in UCr and CCr, indicating obvious renal failure. On the other hand, endogenous antioxidants SOD, GSH-Px were reduced, whereas MDA was increased. However, treatment of T2DN rats with simvastatin restored renal changes in different aspects. Our results showed that STZ-induced T2DN could be attenuated by simvastatin. The renoprotective effects of simvastatin was indicated by improvements in kidney function parameters, and was attributed by its lipid-lowering effect as well as its anti oxidative stress, anti-inflammatory properties without having noticeable influence on glycemic control. Simvastatin ameliorates low-dose Streptozotocin induced type 2 diabetic nephropathy in an experimental rat model. PMID- 26131266 TI - Vascular endothelial growth factor polymorphisms and lung cancer risk. AB - The VEGF polymorphisms has been implicated in the susceptibility to lung cancer, but the results are not conclusive. The aim of this study is to investigate the association between the VEGF polymorphisms and the risk of lung cancer by meta analysis. We searched PubMed, Embase, CNKI and Wanfang databases. A total of 7 case-control studies were included in this meta-analysis. We found that VEGF rs833061 polymorphism showed no significant association with lung cancer risk. Subgroup analysis on race suggested that CC genotype was significantly associated with lung cancer risk in Asian population. We found that VEGF rs699947 polymorphism showed significant association with lung cancer risk. Subgroup analysis on race showed that VEGF rs699947 polymorphism increased lung cancer risk in Asians. In conclusion, this meta-analysis suggested that the VEGF rs699947 is associated with increased risk of lung cancer. PMID- 26131267 TI - Association between RAD51 polymorphisms and susceptibility of head and neck cancer: a meta-analysis. AB - BACKGROUND: The associations between RAD51 gene polymorphisms (G135C and G172T) and risk of head and neck cancer (HNC) have been investigated, but the results are controversial. The aim of this study was to provide a more precise estimation of its relationship with HNC using a meta-analysis. METHODS: Relevant studies were retrieved from the PubMed, Excerpta Medica Database, and China National Knowledge Infrastructure. Strict selection and exclusion criteria were determined, and the odds ratio (OR) with a 95% confidence interval (CI) was used to assess the strength of the association between RAD51 polymorphisms and HNC risk. RESULTS: Six studies were eligible for RAD51 G135C (1593 cases and 1719 controls), and three studies were eligible for RAD51 G172T (997 cases and 979 controls). In the overall population, significant association between RAD51 G135C polymorphism and HNC risk was observed under allele model (C vs G: OR = 1.21, 95% CI = 1.04-1.41, P = 0.015). In the subgroup analysis by smoking status, a significant association was found among smokers (C vs G: OR = 1.59, 95% CI = 1.25 2.04; GC vs GG: OR = 2.29, 95% CI = 1.29-4.05; GC + CC vs GG: OR = 2.08, 95% CI = 1.56-2.78). When stratified based on drinking status, a significant association was found among drinkers(C vs G: OR = 1.60, 95% CI = 1.21-2.11; GC vs GG: OR = 2.50, 95% CI = 1.16-5.38; GC + CC vs GG: OR = 2.17,95% CI = 1.56-3.01). However, no significant association with HNC risk was demonstrated when stratified based on source of control and ethnicity. For G172T polymorphism, the results showed no significant risk association in overall analysis. In the subgroup analysis by ethnicity, the result suggested that a decreased HNC risk was found among Caucasians (T vs G: OR = 0.82, 95% CI = 0.72-0.95; TT vs GG: OR = 0.62, 95% CI = 0.46-0.84; TT vs GT + GG: OR = 0.64, 95% CI = 0.49-0.84). CONCLUSION: This meta analysis suggested that RAD51 G135C is associated with increased HNC risk, especially among smokers and drinkers, while G172T polymorphism may play a protective role against HNC among Caucasians. Larger-scale and well-designed studies are needed to further clarify the association. PMID- 26131268 TI - Diagnostic value of strain ratio measurement in differential diagnosis of thyroid nodules coexisted with Hashimoto thyroiditis. AB - OBJECTIVE: To evaluate the differential diagnostic potential of lesion stiffness assessed by the sonoelastographic strain index ratio (SR) for thyroid nodules coexist with Hashimoto thyroiditis (HT). METHODS: A total of 50 focal thyroid nodules from 36 patients with HT (mean age 38.4 years; range 19-77) scheduled for fine-needle aspiration or thyroid surgery were included. After a routine conventional ultrasound evaluation, real-time ultrasound elastography examinations were performed. Strain and area ratios of each lesion were calculated within the same machine. Histological diagnosis was used as the reference standard. The elastography images were scored according to the Asteria elasticity score. The area under the curve (AUC) and cut-off point were obtained by receiver operating curve (ROC). Sensitivity, specificity and accuracy were compared. RESULTS: A total of 38 nodules were benign and 12 were malignant on pathology. The mean strain ratios of benign and malignant lesions were 2.89 and 7.83 respectively. When a cut-off point of 5.03 was used, SR had a sensitivity of 75.0%, a specificity of 92.1% and an accuracy of 84.0%. The AUC values were 0.836. The diagnostic accuracy of the SR was superior to that of elastographic score. CONCLUSION: Real-time elastography is a promising tool for differential diagnosis of thyroid nodules coexist with HT, and SR measurement could be an effective predictor. The best cut-off point for benign and malignant nodules in patients with HT was 5.03. PMID- 26131269 TI - Effect of combination therapy of propofol and sevoflurane on MAP2K3 level and myocardial apoptosis induced by ischemia-reperfusion in rats. AB - To investigate the mechanism of combination therapy of propofol and sevoflurane on MAP2K3 level and myocardial apoptosis induced by ischemia-reperfusion (IR) in rat. A total of 30 SD rats were randomly separated into 3 groups: normal, IR (ligation of left coronary artery), and IR+ propofol and sevoflurane (IR+P+S). Different methods were used to detect the serum index associated IR injury. TUNEL assay was used to analyze the apoptotic cells of rat heart tissues. qRT-PCR was used to analyze the mRNA levels of cell apoptosis related proteins such as Bcl-2, Bax, and MAP2K3. Western blotting was used to detect the expression of Bcl-2, Bax, MAP2K3, and Caspase-3 of heart tissues. Compared with normal group, serum LDH, cTnI, and CK-MB levels in IR group were significantly increased with time increasing (P<0.05), while that in IR+P+S group were significantly decreased compared with that in IR group (P<0.05). The percentage of apoptotic cells of heart tissue in IR+P+S group was larger than that in IR group (P<0.05). Compared with IR group, mRNA expression of MAP2K3 and Bax were significantly decreased with Bcl-2 was significantly increased in IR+P+S group (P<0.05). Also, expression of MAP2K3, Caspase-3, and Bcl-2 in IR+P+S group were statistically lower while Bax was statistically higher than that in IR group (P<0.05). Our study suggested that combination therapy of propofol and sevoflurane may protect myocardial cells from damage during IR through decreasing MAP2K3 level and reducing cell apoptosis via Bcl-2/Bax pathway. PMID- 26131270 TI - Construction of the recombinant vaccine based on T-cell epitope encoding Der p1 and evaluation on its specific immunotherapy efficacy. AB - Specific immunotherapy (SIT) is currently recognized as the only etiological therapy to ameliorate asthmatic symptom. The current study was aimed at evaluating the immune effect of vaccine MAT3T designed on MHCII pathway, which includes T cell fusion peptide encoding Dermatophagoides pteronyssinus class 1 allergen (Der p1). We initially cloned the nucleotide sequences of TAT, IhC and 3 segments of T cell epitope coding for Der p1, and reassembled these sequences in linear manner to form fusion gene named MAT3T, which was applied to immunize the asthmatic models of mice induced by Der p1 allergen for tentative SIT. ELISA results showed that MAT3T was able to increase the level of IFN-gamma in BALF and allergen specific antibody IgG2a in serum, while decrease the level of IL-13 in BALF and allergen specific antibody IgE and IgG1. Pathological confirmation further revealed that the inflammatory reactions and inflammatory cell infiltration were totally reduced in lung tissue of mice after MAT3T treatment. Our results show that the recombinant allergen MAT3T can effectively correct the imbalance of Th1/Th2, and MAT3T may be used as candidate vaccine against asthma on SIT basis. PMID- 26131271 TI - Non invasive ventilation to prevent reintubation. Key methodological concerns in cardiothoracic unit. PMID- 26131272 TI - Inhibition of ERK5 enhances cytarabine-induced apoptosis in acute myeloid leukemia cells. AB - BACKGROUND AND AIMS: Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Phospho-ERK5 (p ERK5) plays a novel role in chemoresistance in some cancer cells and this pathway is a central mediator of cell survival and apoptotic regulation. The aim of this study was to investigate the effect of a specific ERK5 small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug cytarabine. METHODS: The cells were transfected with siRNAs using LipofectamineTM 2000 transfection reagent. Relative ERK5 mRNA and protein levels were measured by quantitative real-time PCR, immunocytochemical assay, and Western blotting, respectively. The cytotoxic effects of cytarabine and ERK5 siRNA, alone and in combination, on leukemic cells were determined using colony formation and MTT assay. Apoptosis was assessed by ELISA cell death assay. RESULTS: ERK5 siRNA markedly reduced both mRNA and protein expression levels leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, ERK5 siRNA synergistically increased the cell toxic effects of cytarabine. CONCLUSIONS: Our study suggests that down-regulation of ERK5 by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, ERK5 siRNA may be an effective adjuvant in AML chemotherapy. PMID- 26131273 TI - Neovibsanin B inhibits human malignant brain tumor cell line proliferation and induces apoptosis. AB - The present study was designed to examine the effect of neovibsanin B on glioma cell viability, apoptosis and on the survival time in mice bearing tumor xenografts. The results demonstrated that neovibsanin B significantly reduced the cell viability of GL261-NS and GL261-AC cells in a dose-dependent manner. However the inhibition of proliferation was more significant in GL261-NS cells. The IC50 value of neovibsanin B against GL261-NS and GL261-AC cells is 5 and 25 nM, respectively. The inhibitory effect of neovibsanin B on cell growth was more effective than that of vincristine (VCR) (P < 0.05). We also observed a significant decrease in sphere-forming ability of GL261-NS cells on treatment with neovibsanin B. The number of colonies formed by GL261-NS cells on treatment with neovibsanin B, VCR and DMSO were 3.34 +/- 1.02, 12.53 +/- 3.46 and 61.34 +/- 9.89% respectively after 7 days. The flow cytometry revealed a marked increase in apoptotic cell death of GL261-NS cells on treatment with neovibsanin B. The western blots showed a significant decrease in the level of activated caspase-3 on treatment with neovibsanin B after 24 h. In addition, neovibsanin B increased the median survival time of glioma-bearing mice (P < 0.05). Therefore, neovibsanin B effectively inhibits glioma cell viability by inducing apoptosis, and can be a potent therapeutic agent for the treatment of malignant glioma. PMID- 26131274 TI - A prospective, randomized trial of pancreatectomy combined with isolated hepatic perfusion via a dual route or conventional postoperative adjuvant therapy in patients with advanced pancreatic head carcinoma. AB - Prognosis of locally advanced pancreatic head carcinoma after Whipple remains poor. This study is to investigate the efficacy and safety of regional lymphadenectomy and chemotherapy of isolated hypoxic perfusion (IHP) via dual route, and to analyze the effect for survival period. Consecutive patients subjected to our department from January 1, 2006 to December 31 2011 for locally advanced pancreatic head carcinoma were prospectively divided into two groups according to therapeutic modality, and clinical and follow-up data was recorded. In study group, operation duration and postoperative stay time were shorter, blood loss and blood transfusion were less, and incidence of complications was lower. The mean and median survival time was 17.4 +/- 0.76 months and 18.0 months in study group, longer than control group of 14.1 +/- 0.85 months and 17.6 months. Regional lymphadenectomy can be performed with low mortality and morbidity, and combined postoperative IHP via dual-route can improve survival time. PMID- 26131275 TI - Saikosaponin-d protects renal tubular epithelial cell against high glucose induced injury through modulation of SIRT3. AB - Saikosaponin-d (Ssd) is one of the major pharmacologically active molecules present in Bupleurum falcatum L, a medical herb against inflammatory diseases in the traditional Chinese medicine. In the current study, we investigated the protective activity of Ssd on diabetic nephropathy along with the underlying mechanisms using renal tubular epithelial cell line (NRK-52E). Our study showed that high glucose stimulation significantly increased NRK-52E cell proliferation. Ssd administration dramatically inhibited high glucose-induced proliferation and DNA synthesis in NRK-52E cell. In addition, high glucose treatment resulted in oxidative stress as shown by increased production of ROS, higher concentration of MDA, and decreased activity of SOD. However, incubation with Ssd reversed such changes in NRK-52E cells. On the molecular level, Ssd also increased the mRNA levels of IDH2 and MnSOD. Moreover, Ssd-treated NRK-52E cells displayed a dramatic enhancement in SIRT3 expression both at mRNA and protein levels. Down regulation of SIRT3 abolished the protective effects of Ssd on NRK-52E cells. These findings demonstrated that Ssd protected renal tubular epithelial cell against high glucose induced injury via upregulation of SIRT3. PMID- 26131276 TI - Application of modified R.E.N.A.L. nephrometry score system in evaluating the retroperitoneal partial nephrectomy for T1 renal cell carcinoma. AB - OBJECTIVE: This study aims to investigate the application of the modified R.E.N.A.L. nephrometry score system in evaluating the operation difficulty of retroperitoneal partial nephrectomy in T1 renal cell carcinoma patients. METHODS: A total of 52 patients with T1 renal cell carcinoma were enrolled. They all had retroperitoneal partial nephrectomy. Their clinical data was retrospectively analyzed. R.E.N.A.L. nephrometry score system was modified based on the features of retroperitoneal partial nephrectomy. The specificity, sensitivity and Youden index were compared between R.E.N.A.L. nephrometry score system and the modified R.E.N.A.L. nephrometry score system. The effect of the modified R.E.N.A.L. nephrometry score system on perioperative outcomes was analyzed. RESULTS: Three degrees of operation difficulty were defined by the modified R.E.N.A.L. nephrometry score system, which included the low, medium and high degree of operation difficulty. The specificity, sensitivity and Youden index of the modified R.E.N.A.L. nephrometry score system were better than those of the original R.E.N.A.L. nephrometry score system. Compared with low degree of operation difficulty, patients with medium and high degree of operation difficulty had significantly higher levels of operative time, warm ischemia time, and intraoperative blood loss (P < 0.05). And, the levels of operative time, warm ischemia time, and intraoperative blood loss in patients with high degree were significantly higher than those in patients with medium degree (P < 0.05). CONCLUSIONS: The modified R.E.N.A.L. nephrometry score system has a good effect in evaluating the operation difficulty of retroperitoneal partial nephrectomy. PMID- 26131277 TI - Association between serum carcinoembryonic antigen level and oxidative stress parameters among diabetic females. AB - In this study we intended to determine serum level of the carcinoembryonic antigen (CEA) and to find out the correlation with oxidative stress parameters among diabetic female in comparison to control subjects. METHODS: A total of 120 Saudi (type 2 diabetic "T2DM", n = 60 and healthy non-diabetic, n = 60) nonsmokers females were enrolled in this study. Body mass index (BMI) was estimated using weight and height; CEA, superoxide dismutase (SOD), 8-hydroxy deoxyguanosine (8-OHDG), malondialdehyde (MDA) were performed using enzyme-linked immunosorbent assay (ELISA) kits. Blood glucose was estimated by GOD/POD method and, glycated haemoglobin (HbA1c) by immunoturbidimetric method. RESULTS: The student's t-test showed significant differences between the diabetics and controls in CEA, blood glucose, age, oxidative stress markers. Moreover, Pearson's correlation coefficient (r) indicated significant correlations between CEA and age, BMI, blood glucose, HbA1, and MDA. No significant correlation was found between CEA and 8-OHdG, SOD. CONCLUSIONS: In this study we confirmed that CEA influence with components of type 2 diabetes and glycemic control. We found correlation between Lipid peroxidation and CEA among diabetic female in comparison to control subjects. PMID- 26131278 TI - Expression of matrix metalloproteinase-9, cyclooxygenase-2 and vascular endothelial growth factor are increased in gastrointestinal stromal tumors. AB - This study is to investigate the expression of matrix metalloproteinase-9 (MMP 9), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST). Immunohistochemistry was performed to detect the expression of MMP-9, COX-2 and VEGF. The expression of MMP-9, COX-2 and VEGF was compared among different clinicopathological features of GIST. Spearman rank correlation analysis was conducted to analyze the correlation among MMP-9, COX-2 and VEGF. The positive expression rates of MMP-9, COX-2 and VEGF were 76.9%, 84.6% and 82.7%. The expression levels of MMP-9, COX-2 and VEGF were significantly different among the clinicopathological features of growth pattern, tumor diameter, metastasis, mitotic count and central necrosis (P < 0.05). Their expression levels were higher in GIST tissues with higher levels of malignancy, tumor size, metastasis, mitotic count and central necrosis. However, their expression levels were not significantly different among age, gender, primary tumor site or CD117 expression. Additionally, there were positive correlations between COX-2 and VEGF (r = 0.612, P < 0.01), between COX-2 and MMP-9 (r = 0.592, P < 0.05), and between MMP-9 and VEGF (r = 0.690, P < 0.01). MMP-9, COX-2 and VEGF expression levels are increased in GIST tissues and related with clinicopathological features of GIST. PMID- 26131279 TI - Stathmin is a potential molecular marker and target for the treatment of gastric cancer. AB - OBJECTIVE: This study is to investigate the expression levels of stathmin in tissues of gastric cancer, and evaluate the therapeutic effects of stathmin antisense oligodeoxynucleotide (ASODN) and/or docetaxel in human gastric cancer cells. METHODS: Immunohistochemistry was performed to detect the expression levels of stathmin in gastric cancer and adjacent tissues. Stathmin ASODN was transfected into gastric cancer SGC 7901 cell lines. The cell proliferation was assessed with the MTT assay, and the inhibitory rates were calculated. RT-PCR and Western blot analysis were performed to detect the mRNA and protein expression levels of stathmin, respectively. The synergistic effects of stathmin ASODN and docetaxel were evaluated. The efficacy and clinical benefit rates of the treatment of docetaxel combined with stathmin evaluation were investigated and compared. RESULTS: Our results showed that the expression of stathmin was elevated in gastric cancer tissues, indicating a possible association between the stathmin expression and the disease occurrence. The MTT assay and tumor growth experiment revealed that stathmin ASODN significantly inhibited the proliferation of gastric cancer cells, both in vitro and in vivo. Furthermore, stathmin ASDON enhanced the inhibitory effects of docetaxel on the proliferation of gastric cancer cells, indicating a synergistic effect for the combination treatment. Importantly, docetaxel treatment was more effective for stathmin-negative gastric cancer patients, compared with stathmin-positive patients. CONCLUSION: Stathmin expression provides evidence for the treatment planning for gastric cancers. Stathmin might be a potential molecular marker and target for the treatment of gastric cancer. PMID- 26131280 TI - HDAC5 promotes colorectal cancer cell proliferation by up-regulating DLL4 expression. AB - The histone deacetylase (HDACs) family contains a family of enzymes, which are involved in modulating a wide range of cellular processes, such as proliferation, differentiation, apoptosis, and cell cycle progression. However, the biological function of HDAC5 in colorectal cancer has not been well established. In the current research, our data showed that the mRNA and protein levels of HDAC5 were up-regulated in human colorectal cancer cell lines. CCK-8 assay showed that overexpression of HDAC5 significantly promoted the proliferation of colorectal cancer cell lines including SW480 and HCT116. On the contrary, HDAC5 knockdown using small interfering RNA suppressed cell growth in colorectal tumor cells. At the molecular level, we demonstrated that HDAC5 promoted the expression of DLL4. In addition, down-regulation of DLL4 diminished the proliferative effects of HDAC5 in human colorectal cancer cells. Taken together, these results suggest that HDAC5 elevates the proliferation of colorectal cancer cells through up regulation of DLL4. The current study might provide novel potential therapeutic targets in the treatment of colorectal cancer. PMID- 26131281 TI - Evaluation of photodynamic therapy using topical aminolevulinic acid hydrochloride in the treatment of condylomata acuminate. AB - OBJECTIVES: To investigate the efficacy and safety of topical application of 5 aminolaevulinic acid (ALA) photodynamic therapy (PDT) for the treatment of condylomata acuminata (CA) in larger population. METHODS: Patients with CA were given a treatment of ALA-PDT once a week for 3 weeks and followed up at 4, 8, 12 and 24 weeks after the treatment finished. RESULTS: In 531 patients, a clearance rate was observed 95.27%. The rates rouse with PDT cycles. The clearance rate of three PDT cycles was significant higher than one PDT cycles (P < 0.001) and two PDT cycles (P < 0.001). The clearance rate (88.73%) of small lesions (diameter small than 5mm) was significant higher than that (97.74%) of larger lesions (P < 0.001). The clearance rate varied with the location of the lesions. The clearance rate of urethral meatus was highest and that of perianal was lowest. Follow-up for patients with complete response lasted for 24 weeks. The recurrence rate was 5.65%, 11.30%, 15.07%, 15.44% and 16.20% after 1, 4, 8, 12 and 24 weeks. The recurrence rate varied with the location of the lesions. The recurrence rate of perianal was highest and that of labium was lowest. The side effects mainly included flare, pain, erosion, ulcer, and hyperpigmentation. The adverse reaction rate was 7.72%, 8.10%, 2.26%, 0.94% and 0.19%. Sexual dysfunction and urethral malformations were not observed during the 24 weeds visit. CONCLUSION: Topical application of ALA-PDT is a simple and as effective therapy with a lower incidence of adverse effects in the treatment of condylomata acuminata. PMID- 26131282 TI - Transrectal real-time elastography-guided transperineal prostate biopsy as an improved tool for prostate cancer diagnosis. AB - OBJECTIVES: The aim of this study is to determine the utility of transrectal real time elastography (TRTE)-guided prostate biopsies in patients subjected to transrectal ultrasound (TRUS)-guided transperineal prostate biopsies. MATERIALS AND METHODS: A total of 108 consecutive patients suspicious for prostate cancer (PCa) with elevated serum prostate specific antigen (PSA) level > 4 MUg/L or abnormal findings on digital rectal examination (DRE) were enrolled in this study. All patients were sequentially underwent 10-cores systematic biopsy and TRTE-guided targeted biopsy. The detection rate of the TRTE-guided targeted biopsy was compared with that of the TRUS-guided 10-cores systematic biopsy, in combination with prostate biopsy pathology. RESULTS: 38 cases among 108 suspicious patients were diagnosed as PCa using the TRUS-guided 10-cores systematic biopsy with a detection rate of 35.2%. Subsequently, a further increase of 13.9% (15/108, P = 0.039) in PCa detection was obtained by the TRTE guided targeted biopsy. The overall detection rate for PCa was 49.1% (53/108). A total of 1296 cores were sampled among the 108 patients, including 1080 cores for the 10-cores systematic biopsy and 216 cores for the TRTE-guided targeted biopsy cores. The positive rate of the TRTE-guided targeted biopsy was significantly higher than that of the TRUS-guided 10-cores systematic biopsy (50.9% versus 14.1%, P < 0.0001). CONCLUSIONS: TRTE-guided targeted biopsy could be used as a complement to significantly improve the detection rate for PCa in clinical setting. PMID- 26131283 TI - Probiotics improve efficacy and tolerability of triple therapy to eradicate Helicobacter pylori: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: Gastric colonization by Helicobacter pylori is linked to a host of diseases, but eradication rates have declined in recent years. Some experimental studies suggest that probiotics may inhibit growth of H. pylori. This investigation was conducted to assess the impact of probiotics on both efficacy and tolerability of triple therapy to eradicate H. pylori. METHODS: PubMed, Web of Science, and the Cochrane Collaboration were searched for relevant articles published through August 31, 2014. All analytics relied on commercially available software (Stata 11). RESULTS: Twenty-three studies (N = 3900) qualified for meta analysis. Pooled H. pylori eradication rates for triple therapy used alone and with added probiotics were 1464/2026 (72.26%; 95% CI, 67.66%-74.13) and 1513/1874 (80.74%; 95% CI, 74.68%-82.76%), respectively (odds ratio [OR] = 0.58; 95% CI, 0.50-0.68). Loss of appetite was similar in both groups (OR = 0.94; 95% CI, 0.61 1.45), but most adverse events (nausea, diarrhea, epigastric pain, vomiting, taste distortion, and skin rash) were mitigated through addition of probiotics. Publication bias was not evident, as indicated by Begg's and Egger's tests. CONCLUSIONS: Probiotics may improve the efficacy of triple therapy in eradicating gastric H. pylori and alleviate most treatment-related adverse events. PMID- 26131284 TI - Trigeminal neuralgia increases cerebral blood flow in a focal cerebral ischemic model in rats. AB - OBJECTIVE: To investigate the influences of trigeminal neuropathic pain on the cerebral blood flow in a ET-1 focal cerebral ischemia model. METHODS: Male Sprague-Dawley (SD) rats (220-260 g) were randomly divided into a model group (trigeminal neuralgia, TN group) and a sham operation group (sham group). The TN group received bilateral infraorbital nerve chronic constriction surgery, and the sham group only underwent exposure of the infraorbital nerve. The mechanical pain threshold of the rats was continuously monitored for 30 days post surgery. On postoperative day 30, the animals were anesthetized, and 3 MUL (120 pM/MUL) ET-1 was injected into the surroundings of the middle cerebral artery (MCA) to establish a cerebral focal ischemia-reperfusion injury model in rats. The changes in cerebral blood flow of these two groups were monitored 30 min after the injection of ET-1. RESULTS: The mechanic pain threshold values between rats in the two groups were not significantly different (P>0.05). The threshold value in the TN group on postoperative day 9 significantly decreased compared with that before surgery (P<0.01). Between postoperative days 9 and 30, the pain threshold values in the TN group were significantly lower than those in the sham group (P<0.01). From postoperative day 10, the mean arterial pressure in the TN group significantly increased compared with that before surgery (P<0.05), and the blood pressure (BP) in the TN group was higher than that in the sham group between postoperative days 10 and 30 (P<0.05). After 75 min of ET-1 microinjection, the cerebral blood flow in the rat frontal cortex exhibited reperfusion, and the cerebral blood flow in the TN group was significantly higher than that in the sham group (P<0.05). In addition, the content of calcitonin gene-related peptide (CGRP) in the blood of rats in the TN group was significantly higher than that in the sham group (P<0.05). CONCLUSIONS: Trigeminal neuropathic pain may increase the mean arterial pressure and the content of CGRP in the plasma of rats, thus increasing the cerebral blood flow in the frontal cortex of the ET-1 ischemia reperfusion model. PMID- 26131285 TI - Predictive value of MGMT promoter methylation status in Asian and Caucasian patients with malignant gliomas: a meta-analysis. AB - BACKGROUND: The prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter status for survival of patients with malignant gliomas remains controversial. Thus, the meta-analysis was performed in order to identify the impact of MGMT expression on prognosis of malignant gliomas. METHOD: An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases. Version 12.0 STATA software was used for the current meta-analysis. Hazard ratios (HRs) with their corresponding 95% confidence interval (95% CI) were also calculated to clarify the correlation between MGMT expression and the prognosis of malignant gliomas. RESULTS: Final analysis of 2,377 malignant gliomas patients from 32 clinical studies was performed. The meta-analysis results show that MGMT promoter group and unmethylated MGMT group has a significant difference (all P < 0.01). Combined HR of MGMT suggests that the methylated MGMT group has a longer overall survival than the unmethylated MGMT group (P < 0.01), but the Asians don't present a difference between the two groups. CONCLUSION: The meta-analysis study shows that the elevated MGMT promoter group may have a better prognosis in malignant gliomas patients, but the Asians don't have a better prognosis. PMID- 26131286 TI - Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells. AB - To investigate the effect of different concentrations of inhibitors rapamycin, saracatinib, linsitinib and JNJ-38877605 on PC-3 cells with CCK-8 assay, respectively. PC-3 cells were incubated with different concentrations of rapamycin, saracatinib, linsitinib and JNJ-38877605, respectively, for 48 h at 37 degrees C, the concentrations of rapamycin were 5 nM, 10 nM, 20 nM, 50 nM, 75 nM, 100 nM; Saracatinib: 0.125 nM, 0.25 nM, 0.5 nM, 1 nM, 2.5 nM, 5 nM; Linsitinib: 2 nM, 5 nM, 10 nM, 20 nM, 40 nM, 60 nM; JNJ-38877605: 0.125 nM, 0.5 nM, 1 nM, 2.5 nM, 5 nM, 10 nM. The proliferation of PC-3 cells was examined by CCK-8. Different concentrations of inhibitor rapamycin remarkably inhibited PC-3 cell proliferation after 48 h (P<0.05), inhibitory action did not change significantly from 5 nM-100 nM; different concentrations of saracatinib, linsitinib and JNJ 38877605 did not inhibit PC-3 cell proliferation after 48 h. Rapamycin treatment at low concentration can inhibit the proliferation of PC-3 cells, while saracatinib, linsitinib and JNJ-38877605 do not inhibit PC-3 cell proliferation. PMID- 26131287 TI - T cell activation is reduced by the catalytically inactive form of protein tyrosine phosphatase SHP-2. AB - Src-homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is a ubiquitously expressed cytosolic tyrosine phosphatase implicated in many different signaling pathways involving cytokine receptors and T and B cell receptors; however, the precise functional role of SHP-2 in T cell signaling is not entirely clear. In this study, we overexpressed a catalytically inactive form of SHP-2 with a classic cysteine 459-to-serine mutation (dnSHP-2) to elucidate the in vivo effects of SHP-2 on T cells. We found that mice overexpressing dnSHP-2 showed reduced T cell activation, presumably due to increased tyrosine phosphorylation of Grb2-binding protein (Gab2) and inhibition of mitogen-activated protein kinase (MAPK) activity. SHP-2 appears to be a positive regulator of the MAPK pathway in T cells, likely through coupling of the multimeric complex to the Ras/MAPK pathway. However, SHP-2 does not appear to affect T cell antigen receptor (TCR) evoked calcium mobilization, stress-activated protein kinase/c-jun N-terminal kinases (SAPK/JNKs) activation, or overall tyrosine phosphorylation. PMID- 26131288 TI - Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis. AB - Metabolic alkalosis commonly results from excessive hydrochloric acid (HCl), potassium (K(+)) and water (H2O) loss from the stomach or through the urine. The plasma anion gap increases in non-hypoproteinemic metabolic alkalosis due to an increased negative charge equivalent on albumin and the free ionized calcium (Ca(++)) content of plasma decreases. The mean citrate load in all patients was 8740+/-7027 mg from 6937+/-6603 mL of transfused blood products. The citrate load was significantly higher in patients with alkalosis (9164+/-4870 vs. 7809+/-3967, P < 0.05). The estimated mean total citrate administered via blood and blood products was calculated as 43.2+/-34.19 mg/kilogram/day. In non-massive and frequent blood transfusions, the elevated carbon dioxide output has been shown to occur. Due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis + respiratory acidosis and electrolyte imbalance may develop, blood transfusions may result in certain complications. PMID- 26131289 TI - Comparison of peripheral blood T lymphocyte immune function among venous thromboembolism patients with and without infection and patients with simple infection. AB - OBJECTIVE: To investigate the differences of T lymphocyte subgroups and high sensitivity C reactive protein (HsCRP) levels among patients with venous thromboembolism (VTE), VTE patients with infection, simple infection patients and the normal controls. METHOD: 289 patients were enrolled in this study and divided into control group, VTE group, VTE with infection group and simple infection group. RESULT: Compared with the control group, the serum levels of CD3(+), CD4(+), CD8(+) T lymphocytes significantly decreased and CD4(+)/CD8(+) ratio significantly increased in simple infection group (P < 0.05); CD3(+) and CD8(+) T lymphocytes significantly decreased and CD4(+)/CD8(+) ratio significantly increased in VTE and VTE with infection group (P < 0.05); the proportion of declined CD3(+) and CD8(+) T lymphocytes increased, and the proportion of increased CD4(+)/CD8(+) ratio statistically elevated in three disease groups. As an important inflammatory factor, all HsCRP levels in three disease groups significantly increased when compared with the control group. CONCLUSION: Immune dysfunction exists in both of VTE and infection patients, while VTE patients tend to be accompanied with infections. The changes of T lymphocyte subgroups in VTE patients, who were independent from infection, could cause T lymphocyte immune dysfunction, suggesting that there were abnormalities of T lymphocyte immune function in VTE itself. The overall T lymphocyte functions of recognizing antigens and transducing activation signals decline in VTE patients. Besides, the function of T lymphocyte of directly killing virus microbes declines significantly and the inflammatory mechanisms are involved in the occurrence and development of venous thrombosis. PMID- 26131290 TI - Is dabigatran efficacy enough to prevent stroke in atrial fibrillation patient with high CHADS2 score during peri-procedural catheter radiofrequency ablation? A case report with literature review. AB - Atrial fibrillation (AF) is a major cause of thromboembolic (TE) events including stroke and transient ischemic attacks, catheter radiofrequency ablation (CA) has been demonstrated to effectively eliminate AF in majority of patients. During the peri-procedural CA of AF, dabigatran, a reversible direct thrombin inhibitor, has been proved as safe and efficacy as warfarin in the prevention of thromboembolic complication. However, for patients with CHADS2 score >=3, sometimes dabigatran may not be an ideal substitute of warfarin. The current study presents delayed stroke occurred in a middle-aged AF patient with high CHADS2 score who had undergone successful CA of AF being on dabigatran, trans esophageal echocardiogram (TEE) detected a clot in the left atrium appendage (LAA) and magnetic resonance image (MRI) indicated stroke of left basal ganglia, therefore anticoagulant was switched to warfarin with well controlled international normalization ratio (INR) ranging from 2.0-3.0 and the patient eventually recovered without any TE events during the subsequent follow-up. PMID- 26131291 TI - Expression of microRNAs differed in the omental adipose tissue of obese rats. AB - OBJECTIVE: To establish obese rat models by high-fat diet, screen microRNAs by microarray in the omental adipose tissue, and find out differential expression of microRNAs in obese rats, for further understanding the role of microRNAs as regulating molecules in obesity-induced lipid metabolism disorders. METHODS: 40 male SD rats were randomly divided into normal diet group and high-fat diet group, respectively. After fed for 8 weeks, rats were weighted, measured length and other characteristics were observed. Eye blood was taken to test blood glucose level, blood lipids level, insulin level and other indicators. The omental adipose tissue was measured by electronic analytical scales and saved at 80 degrees C liquid nitrogen. Fat cells were stained by oil red to observe their morphology under microscopy. The expression of microRNAs was screened by microarray, and verified by Real-Time PCR. RESULTS: After high-fat diet for 4 and 8 weeks, some fatty indicators changed, including increased body weight, omental fat weight, triglycerides, total cholesterol, low-density lipoprotein, blood glucose level and insulin level, and decreased high-density lipoprotein, and differential phenotype of fat cells. Besides, by microarray techniques and Real Time PCR, 13 differential expression microRNAs were identified, including 7 up regulated microRNAs (microRNA30a, microRNA7e, microRNA30c, microRNA335, microRNA103, microRNA107, microRNA139-5p), and 6 down-regulated microRNAs (microRNA494, microRNA140, microRNA342-5p, microRNA382, microRNA17-1-3p, microRNA92a). CONCLUSION: Changes in the expression of microRNAs contribute to the pathogenesis of many diseases, including obesity disorders. These alterations can be due to various mechanisms, such as cell proliferation, apoptosis, migration, and differentiation, providing new therapies for diseases. PMID- 26131292 TI - Phylogenetic features of hemagglutin gene in canine distemper virus strains from different genetic lineages. AB - In the present study, the genotype of two Canine distemper virus (CDV) strains, namely, ZJJ-SD and ZJJ-LN, were investigated, based on the whole hemagglutinin (HA) gene. The CDV strains were obtained from two foxes in Shandong Province and Liaoning Province in 2011. Phylogenetic analyses were carried out for 260 CDV strains worldwide, and a statistical analysis was performed in the amino acid substitutions at positions 530 and 549 of the HA protein. Phylogenetic analyses revealed that the two strains, ZJJ-SD and ZJJ-LN, belonged to the CDV Asia I lineage. Site 530 of HA protein was found to be relatively conserved within CDV lineages in different host species by combining the genetic sequence data with the published data from 260 CDV strains worldwide. The data analysis showed a bias toward the predicted substitution Y549H for the non-dog strains in Asia I and Europe lineages. The ratio of site 549 genetic drift in the HA gene were significantly different between dogs and non-dogs in the two lineages. The strain ZJJ-SD, from wild canid, has an Y549H substitution. It is one of three Y549H substitution for wild canids in Asia I lineages. Site 530 of HA protein was not immediately relative to CDV genetic drift from dogs to non-dogs. Statistical analysis indicated that non-dog strains have a high probability to contain Y549H than dog strains in Asia I and Europe lineages. Thus, site 549 is considered important in genetic drift from dogs to non-dogs, at least in Asia I and Europe lineages. PMID- 26131293 TI - The combination of inferior pedicle method and dermal suspension sling technique: one new efficient method for breast reduction. AB - OBJECTIVE: To explore a method of breast reduction which ensures well nipple and areola lactation function, adequate blood supply and good medial fullness and projection. At the same time, this study could evaluate the advantages of the combination of inferior pedicle method and dermal suspension sling technique for breast reduction. METHODS: From 2011.11 to 2013.8, 13 women have undergone breast reduction using utilizing inferior pedicle combined with the dermal suspension sling technique. The inferior pedicle was designed with medial and lateral triangular flaps in the areas where normally be excised. These triangular flaps were deepithelialized and defatted. The flaps were attached to the chest wall above the inferior pedicle to create a dermal "cage". RESULTS: After operation, Sensation of nipple and areola complex, breast projection and shape were sustained during follow-up, of which the median interval was 12 months. No patient had poor projection and bottoming out. CONCLUSION: Dermal suspension and horizontal dermal placation provides a structural foundation to the inferior pedicle. It is an effective method of treatment for breast reduction, in that the sensation and lactation function of nipple and areola complex get further guaranteed, have nice breast projection and shape, and can be applied to all cases of breast reduction. PMID- 26131294 TI - XPC Ala499Val and XPG Asp1104His polymorphisms and digestive system cancer risk: a meta-analysis based on model-free approach. AB - Many studies have reported the association between XPC Ala499Val and XPG Asp1104His polymorphisms and digestive system cancer susceptibility, but the results were inconclusive. We performed a meta-analysis, using a comprehensive strategy based on the allele model and a model-free approach, to derive a more precise estimation of the relationship between XPC Ala499Val and XPG Asp1104His polymorphisms with digestive system cancer risk. For XPC Ala499Val, no significant cancer risk was found in the allele model (OR = 0.98, 95% CI: 0.86 1.11) and with model-free approach (ORG = 0.97, 95% CI: 0.83-1.13). For XPG Asp1104His, there was also no association between this polymorphism and cancer risk in the allele model (OR = 1.03, 95% CI: 0.96-1.11) and with the model-free approach (ORG = 1.04, 95% CI: 0.95-1.14). Therefore, this meta-analysis suggests that the XPC Ala499Val and XPG Asp1104His polymorphisms were not associated with digestive system cancer risk. Further large and well-designed studies are needed to confirm these findings. PMID- 26131295 TI - Dietary vitamin E intake could reduce the risk of lung cancer: evidence from a meta-analysis. AB - BACKGROUND: Quantification of the association between the intake of vitamin E and risk of lung cancer is still conflicting. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of vitamin E intake with the risk of lung cancer. METHODS: Pertinent studies were identified by a search in PubMed and Web of Knowledge up to October 2014. Random-effect model was used to combine study-specific results. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: Ten articles reporting 11 studies (10 prospective studies and 1 case-control studies) involving 4434 lung cancer cases were used in this meta-analysis. The combined relative risk (RR) of lung cancer associated with vitamin E intake was 0.858 (95% CI=0.742-0.991) overall, significant protective associations were also found in America population (RR=0.862, 95% CI=0.715-0.996) and prospective studies (RR=0.913, 95% CI=0.827 0.996). No publication bias was found. CONCLUSIONS: Our analysis indicated that vitamin E intake might decrease the risk of lung cancer, especially in America. PMID- 26131296 TI - Anterior Cruciate Ligament Injury. PMID- 26131297 TI - A Systematic Review of Failed Anterior Cruciate Ligament Reconstruction With Autograft Compared With Allograft in Young Patients. AB - CONTEXT: The advantages of allograft anterior cruciate ligament reconstruction (ACLR), which include shorter surgical time, less postoperative pain, and no donor site morbidity, may be offset by a higher risk of failure. Previous systematic reviews have inconsistently shown a difference in failure prevalence by graft type; however, such reviews have never been stratified for younger or more active patients. OBJECTIVE: To determine whether there is a different ACLR failure prevalence of autograft compared with allograft in young, active patients. DATA SOURCES: EMBASE, MEDLINE, Cochrane trials registry. STUDY SELECTION: Comparative studies of allograft versus autograft primary ACL reconstruction in patients <25 years of age or of high-activity level (military, Marx activity score >12 points, collegiate or semiprofessional athletes). STUDY DESIGN: Systematic review with meta-analysis. LEVEL OF EVIDENCE: Level 3. DATA EXTRACTION: Manual extraction of available data from eligible studies. Quantitative synthesis of failure prevalence and Lysholm score (outcomes in >=3 studies) and I (2) test for heterogeneity. Assessment of study quality using CLEAR NPT and Newcastle-Ottawa Scale (NOS). RESULTS: Seven studies met inclusion criteria (1 level 1; 2 level 2, 4 level 3), including 788 patients treated with autograft tissue and 228 with various allografts. The mean age across studies was 21.7 years (64% male), and follow-up ranged between 24 and 51 months. The pooled failure prevalence was 9.6% (76/788) for autografts and 25.0% (57/228) for allografts (relative risk, 0.36; 95% CI, 0.24-0.53; P < 0.00001; I (2) = 16%). The number needed to benefit to prevent 1 failure by using autograft was 7 patients (95% CI, 5-10). No difference between hamstrings autograft and patella tendon autograft was noted. Lysholm score was reported in 3 studies and did not differ between autograft and allograft. CONCLUSION: While systematic reviews comparing allograft and autograft ACLR have been equivocal, this is the first review to examine young and active patients in whom allograft performs poorly. PMID- 26131298 TI - Association of the Single-Limb Hop Test With Isokinetic, Kinematic, and Kinetic Asymmetries in Patients After Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: Asymmetries persist after anterior cruciate ligament reconstruction (ACLR). Physical performance tests such as the single-limb hop test have been used extensively to assess return-to-sport criteria, as they reproduce dynamic athletic maneuvers. HYPOTHESIS: The single-limb hop is associated with muscle strength and kinematic and kinetic asymmetries in ACLR patients 6 to 9 months after surgery. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-two men with ACLR (mean age, 28.8 +/- 11.2 years) at 6 to 9 months (mean, 7.01 +/- 0.93 months) after surgery completed isokinetic testing in 3 velocities (120, 180, and 300 deg/s) and a kinetic, kinematic, and functional evaluation of the single-limb hop test. Pearson correlation coefficients were used to assess the relationship between the Limb Symmetry Index (LSI) of the single-limb hop distance and each of the outcome variables. RESULTS: There were significant positive correlations between the LSI of the single-limb hop distance and the LSI of the peak extension torque at 120 deg/s (P = 0.044, r = 0.37) and the peak extension torque at 180 deg/s (P = 0.042, r = 0.38) as well as a negative correlation with the peak flexion torque at 180 deg/s (P = 0.043, r = -0.38). The LSI of the single-limb hop test was not correlated with any kinetic or kinematic variable (P > 0.05). CONCLUSION: The findings of the present study demonstrate that distance LSI of the single-limb hop test correlates with isokinetic extension peak torque LSI but not kinetic and kinematic asymmetry. CLINICAL RELEVANCE: The single-limb hop test can be used as an additional tool for the recognition of muscle strength asymmetries but not for kinetic or kinematic asymmetries 6 to 9 months after ACLR. PMID- 26131299 TI - Anterior Cruciate Ligament Reconstruction-Not Exactly a One-Way Ticket Back to the Preinjury Level: A Review of Contextual Factors Affecting Return to Sport After Surgery. AB - CONTEXT: A recently updated meta-analysis of return-to-sport rates after anterior cruciate ligament (ACL) reconstruction demonstrated that 65% of athletes returned to their preinjury level of sport after surgery. The aim of this clinical review was to explore contextual factors associated with returning or not returning to the preinjury level after ACL reconstruction. EVIDENCE ACQUISITION: Data were obtained from peer-reviewed literature via a search of the electronic databases Medline, Embase, CINAHL, and SPORTDiscus from database inception to January 2015. The keywords anterior cruciate ligament and return to sport were used. Additional literature was identified via hand-searching of the reference lists of relevant articles and the ePublication lists of key scientific journals. Random effects meta-analyses were used to pool the results of modifiable contextual factors and to examine their association with returning or not returning to the preinjury level of sport after surgery. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 2. RESULTS: Lower fear of reinjury (standardized mean difference, 0.7), greater psychological readiness to return to sport (standardized mean difference, 1.0), and a more positive subjective assessment of knee function (standardized mean difference, 0.9) favored return to the preinjury level after surgery. CONCLUSION: Returning or not returning to the preinjury level after ACL reconstruction is complex and multifactorial. Screening for potentially modifiable contextual factors, particularly psychological factors, early after ACL injury may help clinicians identify athletes who could be at risk of not returning to the preinjury level of sport and institute interventions that could improve returning to sport. PMID- 26131300 TI - Deficits in Quadriceps Strength and Patient-Oriented Outcomes at Return to Activity After ACL Reconstruction: A Review of the Current Literature. AB - CONTEXT: Side-to-side quadriceps strength deficits are linked to hazardous lower extremity mechanics and reduced function at a time when individuals are returned to activity after anterior cruciate ligament (ACL) reconstruction. As a result, generalized criteria have emerged in the literature, wherein researchers are recommending that patients be cleared for participation once side-to-side differences in strength are <=10% of the noninjured limb. Similar recommendations exist for patient-oriented outcomes (ie, self-reported function and hop tests), where deficits of <=10% are considered ideal at return to activity. It is unclear how many studies actually achieve these clinically recommended results. EVIDENCE ACQUISITION: Articles that reported quadriceps strength deficits as compared to the contralateral limb were collected from peer-reviewed sources available on Medline and Web of Science databases (1990 through August 2014). Search terms included the following: anterior cruciate ligament OR ACL AND muscle weakness, anterior cruciate ligament OR ACL AND strength; return-to-activity AND strength; anterior cruciate ligament OR ACL AND quadriceps. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Average side-to-side strength deficits at 6 months postreconstruction were 23% +/- 8% (range, 3%-40%), while the average at 12 months postsurgery was found to be 14% +/- 6% (range, 3%-28%). The average deficits in self-reported function at 6 months (mean, 14% +/- 5%) and 12 months postsurgery (mean, 13% +/- 6%) were also found to be >10%. Performance on hop tests was found to be less than optimal at 6 months postsurgery (mean, 11% +/- 7%), but improved at 12 months postsurgery (mean, 1.3% +/- 2%). CONCLUSION: This review provides an up-to-date account of the typical deficits in strength and patient-oriented outcomes that exist when formalized physical therapy concludes after ACL reconstruction. Based on the studies included, it seems pertinent that researchers and clinicians continue to investigate interventions capable of improving the recovery of quadriceps strength as well as patient-oriented outcomes as the majority of studies report levels that are well below clinical recommendations. PMID- 26131302 TI - Defending Puts the Anterior Cruciate Ligament at Risk During Soccer: A Gender Based Analysis. AB - BACKGROUND: Soccer athletes are at risk for anterior cruciate ligament (ACL) injury. To date, there are limited studies on the mechanisms of ACL injuries in soccer athletes and no video-based analysis or sex-based comparison of these mechanisms. HYPOTHESIS: There is no difference in ACL injury mechanisms among soccer athletes by sex. STUDY DESIGN: Case series. LEVEL OF EVIDENCE: Level 4. METHODS: Fifty-five videos of ACL injuries in 32 male and 23 female soccer players were reviewed. Most athletes were professionals (22 males, 4 females) or collegiate players (8 males, 14 females). Visual analysis of each case was performed to describe the injury mechanisms in detail (game situation, player behavior, and lower extremity alignment). RESULTS: The majority of ACL injuries occurred when the opposing team had the ball and the injured athlete was defending (73%). Females were more likely to be defending when they injured their ACLs (87% vs 63% for males, P = 0.045). The most common playing action was tackling (51%), followed by cutting (15%). Most injuries occurred due to a contact mechanism (56%) with no significant difference for sex. Females were more likely to suffer a noncontact injury in their left knee (54%) than males (33%) (P = 0.05). CONCLUSION: Soccer players are at greatest risk for ACL injury when defending, especially when tackling the opponent in an attempt to win possession of the ball. Females are more likely to injure their ACLs when defending and are at greater risk for noncontact injuries in their left lower extremity. CLINICAL RELEVANCE: Soccer ACL injury prevention programs should include proper defending and tackling techniques, particularly for female athletes. PMID- 26131301 TI - Anterior Cruciate Ligament Reconstruction Rehabilitation: MOON Guidelines. AB - CONTEXT: Anterior cruciate ligament (ACL) reconstruction rehabilitation has evolved over the past 20 years. This evolution has been driven by a variety of level 1 and level 2 studies. EVIDENCE ACQUISITION: The MOON Group is a collection of orthopaedic surgeons who have developed a prospective longitudinal cohort of the ACL reconstruction patients. To standardize the management of these patients, we developed, in conjunction with our physical therapy committee, an evidence based rehabilitation guideline. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 2. RESULTS: This review was based on 2 systematic reviews of level 1 and level 2 studies. Recently, the guideline was updated by a new review. Continuous passive motion did not improve ultimate motion. Early weightbearing decreases patellofemoral pain. Postoperative rehabilitative bracing did not improve swelling, pain range of motion, or safety. Open chain quadriceps activity can begin at 6 weeks. CONCLUSION: High-level evidence exists to determine appropriate ACL rehabilitation guidelines. Utilizing this protocol follows the best available evidence. PMID- 26131303 TI - Common Dental Injury Management in Athletes. AB - CONTEXT: Orofacial and dental trauma continues to be a commonly encountered issue for the sports medicine team. All sports have some risk for dental injury, but "contact sports" presumably incur more risk. Immediate evaluation and proper management of the most common injuries to dentition can result in saving or restoration of tooth structure. Despite the growing body of evidence, mouth guard use and dental protection have not paralleled the increase in sports participation. EVIDENCE ACQUISITION: A PubMed search from 1960 through April 2012 was conducted, as well as a review of peer-reviewed online publications. RESULTS: Common dental injuries in sports include tooth (crown) fractures; tooth intrusion, extrusion, and avulsion; and temporomandibular joint dislocation. Mouth guards help prevent most injuries and do not significantly affect ventilation or speech if fitted properly. CONCLUSION: A working knowledge of the presentation as well as management of commonly encountered dental trauma in sports is essential to the immediate care of an athlete and returning to play. Mouth guard use should be encouraged for athletes of all ages in those sports that incur significant risk. PMID- 26131304 TI - Effect of Minimalist Footwear on Running Efficiency: A Randomized Crossover Trial. AB - BACKGROUND: Although minimalist footwear is increasingly popular among runners, claims that minimalist footwear enhances running biomechanics and efficiency are controversial. HYPOTHESIS: Minimalist and barefoot conditions improve running efficiency when compared with traditional running shoes. STUDY DESIGN: Randomized crossover trial. LEVEL OF EVIDENCE: Level 3. METHODS: Fifteen experienced runners each completed three 90-second running trials on a treadmill, each trial performed in a different type of footwear: traditional running shoes with a heavily cushioned heel, minimalist running shoes with minimal heel cushioning, and barefoot (socked). High-speed photography was used to determine foot strike, ground contact time, knee angle, and stride cadence with each footwear type. RESULTS: Runners had more rearfoot strikes in traditional shoes (87%) compared with minimalist shoes (67%) and socked (40%) (P = 0.03). Ground contact time was longest in traditional shoes (265.9 +/- 10.9 ms) when compared with minimalist shoes (253.4 +/- 11.2 ms) and socked (250.6 +/- 16.2 ms) (P = 0.005). There was no difference between groups with respect to knee angle (P = 0.37) or stride cadence (P = 0.20). When comparing running socked to running with minimalist running shoes, there were no differences in measures of running efficiency. CONCLUSION: When compared with running in traditional, cushioned shoes, both barefoot (socked) running and minimalist running shoes produce greater running efficiency in some experienced runners, with a greater tendency toward a midfoot or forefoot strike and a shorter ground contact time. Minimalist shoes closely approximate socked running in the 4 measurements performed. CLINICAL RELEVANCE: With regard to running efficiency and biomechanics, in some runners, barefoot (socked) and minimalist footwear are preferable to traditional running shoes. PMID- 26131305 TI - Rates of Deep Venous Thrombosis and Pulmonary Embolus After Anterior Cruciate Ligament Reconstruction: A Systematic Review. AB - CONTEXT: Venous thromboembolic (VTE) disease is thought to be an uncommon but serious problem after anterior cruciate ligament (ACL) reconstruction. Rates of VTE after ACL reconstruction are not well documented. OBJECTIVE: To determine the rates of deep vein thrombosis (DVT) and symptomatic pulmonary emboli (PE) after ACL reconstruction. DATA SOURCES: Five publicly available databases (PubMed, Cochrane Database of Systematic Reviews, Scopus, Embase, and CINAHL Complete) were utilized. STUDY SELECTION: All studies that screened patients for DVT and reported rates of DVT and PE after ACL reconstruction were eligible for inclusion. Level 5 evidence, cadaver, biomechanical, and basic science studies; studies reporting only multiligament reconstruction outcomes; studies where rates of DVT and PE could not be separated out from patients undergoing other types of arthroscopic knee procedures; and classification studies were excluded. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: All study, subject, and surgical data were analyzed. Descriptive statistics were calculated. RESULTS: Six studies met the inclusion criteria, with a mean Modified Colman Methodology Score of 30 +/- 8.22. A total of 692 patients (488 men [70.5%]; mean age, 31.6 +/- 2.82 years; mean follow-up, 7 +/- 18.4 months) underwent ACL reconstruction using either semitendinosus-gracilis autograft (77.6%), bone-patellar tendon-bone (BTB) autograft (22%), or allograft (0.4%). No patient received postoperative pharmacological anticoagulation. Fifty-eight patients (8.4%) had a DVT (81% below knee and 19% above knee), while only 1 patient (0.2%) had a symptomatic PE. When reported, 27% of DVT episodes were symptomatic. CONCLUSION: The rate of DVT after ACL reconstruction in patients who did not receive postoperative pharmacological anticoagulation is 8.4%, while the rate of symptomatic PE is 0.2%. Of the DVT episodes that occurred, 73% were asymptomatic. PMID- 26131306 TI - Clinician Recommendations and Perceptions of Factors Associated With Ankle Brace Use. AB - BACKGROUND: Little information is available regarding the ankle braces orthopaedic sports medicine clinicians recommend or clinicians' concerns that may influence their decisions to recommend use of an ankle brace. HYPOTHESES: (1) Clinicians most frequently recommend lace-up braces with straps. (2) Clinicians who are concerned about potential adverse side effects from ankle brace use are less likely to recommend an ankle brace to prevent ankle sprain injuries. STUDY DESIGN: Descriptive survey study. LEVEL OF EVIDENCE: Level 3. METHODS: Surveys were sent via e-mail to 1000 randomly selected members of the Orthopaedic Section of the American Physical Therapy Association (APTA) and 1000 randomly selected members of the National Athletic Trainers' Association (NATA). A total of 377 individuals responded to the survey. RESULTS: Lace-up braces, specifically lace up braces with straps, were the most frequently recommended type of ankle brace. Regression analyses indicated that the only perceived adverse side effect significantly related to frequency of ankle brace recommendation was a potential negative influence on ankle strength. CONCLUSION: Based on our sample, clinicians recommend lace-up ankle braces with straps most frequently to prevent ankle sprain injuries. Clinicians who are concerned about weakness of ankle musculature may be less likely to recommend use of an ankle brace. CLINICAL RELEVANCE: Clinicians may effectively reduce the number of ankle sprain injuries by recommending an ankle brace use after an initial ankle sprain injury. PMID- 26131307 TI - The Masters Athlete: A Review of Current Exercise and Treatment Recommendations. AB - CONTEXT: With the ever-increasing number of masters athletes, it is necessary to understand how to best provide medical support to this expanding population using a multidisciplinary approach. EVIDENCE ACQUISITION: Relevant articles published between 2000 and 2013 using the search terms masters athlete and aging and exercise were identified using MEDLINE. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 3. RESULTS: Preparticipation screening should assess a variety of medical comorbidities, with emphasis on cardiovascular health in high-risk patients. The masters athlete should partake in moderate aerobic exercise and also incorporate resistance and flexibility training. A basic understanding of physiology and age-related changes in muscle composition and declines in performance are prerequisites for providing appropriate care. Osteoarthritis and joint arthroplasty are not contraindications to exercise, and analgesia has an appropriate role in the setting of acute or chronic injuries. Masters athletes should follow regular training regimens to maximize their potential while minimizing their likelihood of injuries. CONCLUSION: Overall, masters athletes represent a unique population and should be cared for utilizing a multidisciplinary approach. This care should be implemented not only during competitions but also between events when training and injury are more likely to occur. STRENGTH OF RECOMMENDATION TAXONOMY SORT: B. PMID- 26131309 TI - Mesenchymal stem cells: A new diagnostic tool? AB - Mesenchymal stem cells (MSCs) are progenitor cells capable of self-renewal that can differentiate in multiple tissues and, under specific and standardized culture conditions, expand in vitro with little phenotypic alterations. In recent years, preclinical and clinical studies have focused on MSC analysis and understanding the potential use of these cells as a therapy in a wide range of pathologies, and many applications have been tested. Clinical trials using MSCs have been performed (e.g., for cardiac events, stroke, multiple sclerosis, blood diseases, auto-immune disorders, ischemia, and articular cartilage and bone pathologies), and for many genetic diseases, these cells are considered an important resource. Considering of the biology of MSCs, these cells may also be useful tools for understanding the physiopathology of different diseases, and they can be used to develop specific biomarkers for a broad range of diseases. In this editorial, we discuss the literature related to the use of MSCs for diagnostic applications and we suggest new technologies to improve their employment. PMID- 26131310 TI - Contemporary perspective on endogenous myocardial regeneration. AB - Considering the complex nature of the adult heart, it is no wonder that innate regenerative processes, while maintaining adequate cardiac function, fall short in myocardial jeopardy. In spite of these enchaining limitations, cardiac rejuvenation occurs as well as restricted regeneration. In this review, the background as well as potential mechanisms of endogenous myocardial regeneration are summarized. We present and analyze the available evidence in three subsequent steps. First, we examine the experimental research data that provide insights into the mechanisms and origins of the replicating cardiac myocytes, including cell populations referred to as cardiac progenitor cells (i.e., c-kit+ cells). Second, we describe the role of clinical settings such as acute or chronic myocardial ischemia, as initiators of pathways of endogenous myocardial regeneration. Third, the hitherto conducted clinical studies that examined different approaches of initiating endogenous myocardial regeneration in failing human hearts are analyzed. In conclusion, we present the evidence in support of the notion that regaining cardiac function beyond cellular replacement of dysfunctional myocardium via initiation of innate regenerative pathways could create a new perspective and a paradigm change in heart failure therapeutics. Reinitiating cardiac morphogenesis by reintroducing developmental pathways in the adult failing heart might provide a feasible way of tissue regeneration. Based on our hypothesis "embryonic recall", we present first supporting evidence on regenerative impulses in the myocardium, as induced by developmental processes. PMID- 26131311 TI - Corneal stem cells and tissue engineering: Current advances and future perspectives. AB - Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there are many challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed. PMID- 26131312 TI - Stem cell applications for pathologies of the urinary bladder. AB - New stem cell based therapies are undergoing intense research and are widely investigated in clinical fields including the urinary system. The urinary bladder performs critical complex functions that rely on its highly coordinated anatomical composition and multiplex of regulatory mechanisms. Bladder pathologies resulting in severe dysfunction are common clinical encounter and often cause significant impairment of patient's quality of life. Current surgical and medical interventions to correct urinary dysfunction or to replace an absent or defective bladder are sub-optimal and are associated with notable complications. As a result, stem cell based therapies for the urinary bladder are hoped to offer new venues that could make up for limitations of existing therapies. In this article, we review research efforts that describe the use of different types of stem cells in bladder reconstruction, urinary incontinence and retention disorders. In particular, stress urinary incontinence has been a popular target for stem cell based therapies in reported clinical trials. Furthermore, we discuss the relevance of the cancer stem cell hypothesis to the development of bladder cancer. A key subject that should not be overlooked is the safety and quality of stem cell based therapies introduced to human subjects either in a research or a clinical context. PMID- 26131314 TI - Human dental pulp stem cells: Applications in future regenerative medicine. AB - Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and beta cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine. PMID- 26131313 TI - Modeling diseases of noncoding unstable repeat expansions using mutant pluripotent stem cells. AB - Pathogenic mutations involving DNA repeat expansions are responsible for over 20 different neuronal and neuromuscular diseases. All result from expanded tracts of repetitive DNA sequences (mostly microsatellites) that become unstable beyond a critical length when transmitted across generations. Nearly all are inherited as autosomal dominant conditions and are typically associated with anticipation. Pathologic unstable repeat expansions can be classified according to their length, repeat sequence, gene location and underlying pathologic mechanisms. This review summarizes the current contribution of mutant pluripotent stem cells (diseased human embryonic stem cells and patient-derived induced pluripotent stem cells) to the research of unstable repeat pathologies by focusing on particularly large unstable noncoding expansions. Among this class of disorders are Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome, myotonic dystrophy type 1 and myotonic dystrophy type 2, Friedreich ataxia and C9 related amyotrophic lateral sclerosis and/or frontotemporal dementia, Facioscapulohumeral Muscular Dystrophy and potentially more. Common features that are typical to this subclass of conditions are RNA toxic gain-of-function, epigenetic loss-of-function, toxic repeat-associated non-ATG translation and somatic instability. For each mechanism we summarize the currently available stem cell based models, highlight how they contributed to better understanding of the related mechanism, and discuss how they may be utilized in future investigations. PMID- 26131315 TI - Histone deacetylases and cardiovascular cell lineage commitment. AB - Cardiovascular diseases (CVDs), which include all diseases of the heart and circulation system, are the leading cause of deaths on the globally. During the development of CVDs, choric inflammatory, lipid metabolism disorder and endothelial dysfunction are widely recognized risk factors. Recently, the new treatment for CVDs that designed to regenerate the damaged myocardium and injured vascular endothelium and improve recovery by the use of stem cells, attracts more and more public attention. Histone deacetylases (HDACs) are a family of enzymes that remove acetyl groups from lysine residues of histone proteins allowing the histones to wrap the DNA more tightly and commonly known as epigenetic regulators of gene transcription. HDACs play indispensable roles in nearly all biological processes, such as transcriptional regulation, cell cycle progression and developmental events, and have originally shown to be involved in cancer and neurological diseases. HDACs are also found to play crucial roles in cardiovascular diseases by modulating vascular cell homeostasis (e.g., proliferation, migration, and apoptosis of both ECs and SMCs). This review focuses on the roles of different members of HDACs and HDAC inhibitor on stem cell/ progenitor cell differentiation toward vascular cell lineages (endothelial cells, smooth muscle cells and Cardiomyocytes) and its potential therapeutics. PMID- 26131316 TI - Hepatic stem cells: A viable approach for the treatment of liver cirrhosis. AB - Liver cirrhosis is characterized by distortion of liver architecture, necrosis of hepatocytes and regenerative nodules formation leading to cirrhosis. Various types of cell sources have been used for the management and treatment of decompensated liver cirrhosis. Knowledge of stem cells has offered a new dimension for regenerative therapy and has been considered as one of the potential adjuvant treatment modality in patients with end stage liver diseases (ESLD). Human fetal hepatic progenitor cells are less immunogenic than adult ones. They are highly propagative and challenging to cryopreservation. In our earlier studies we have demonstrated that fetuses at 10-18 wk of gestation age contain a large number of actively dividing hepatic stem and progenitor cells which possess bi-potent nature having potential to differentiate into bile duct cells and mature hepatocytes. Hepatic stem cell therapy for the treatment of ESLD is in their early stage of the translation. The emerging technology of decellularization and recellularization might offer a significant platform for developing bioengineered personalized livers to come over the scarcity of desired number of donor organs for the treatment of ESLD. Despite these significant advancements long-term tracking of stem cells in human is the most important subject nowadays in order to answer several unsettles issues regarding the route of delivery, the choice of stem cell type(s), the cell number and the time-point of cell delivery for the treatment in a chronic setting. Answering to these questions will further contribute to the development of safer, noninvasive, and repeatable imaging modalities that could discover better cell therapeutic approaches from bench to bed-side. Combinatorial approach of decellularization and nanotechnology could pave a way towards the better understanding in determination of cell fate post-transplantation. PMID- 26131317 TI - Hair follicle stem cells: In vitro and in vivo neural differentiation. AB - Hair follicle stem cells (HFSCs) normally give rise to keratinocytes, sebocytes, and transient amplifying progenitor cells. Along with the capacity to proliferate rapidly, HFSCs provide the basis for establishing a putative source of stem cells for cell therapy. HFSCs are multipotent stem cells originating from the bulge area. The importance of these cells arises from two important characteristics, distinguishing them from all other adult stem cells. First, they are accessible and proliferate for long periods. Second, they are multipotent, possessing the ability to differentiate into mesodermal and ectodermal cell types. In addition to a developmental capacity in vitro, HFSCs display an ability to form differentiated cells in vivo. During the last two decades, numerous studies have led to the development of an appropriate culture condition for producing various cell lineages from HFSCs. Therefore, these stem cells are considered as a novel source for cell therapy of a broad spectrum of neurodegenerative disorders. This review presents the current status of human, rat, and mouse HFSCs from both the cellular and molecular biology and cell therapy perspectives. The first section of this review highlights the importance of HFSCs and in vitro differentiation, while the final section emphasizes the significance of cell differentiation in vivo. PMID- 26131318 TI - Utility of tricalcium phosphate and osteogenic matrix cell sheet constructs for bone defect reconstruction. AB - AIM: To determine the effects of transplanting osteogenic matrix cell sheets and beta-tricalcium phosphate (TCP) constructs on bone formation in bone defects. METHODS: Osteogenic matrix cell sheets were prepared from bone marrow stromal cells (BMSCs), and a porous TCP ceramic was used as a scaffold. Three experimental groups were prepared, comprised of TCP scaffolds (1) seeded with BMSCs; (2) wrapped with osteogenic matrix cell sheets; or (3) both. Constructs were implanted into a femoral defect model in rats and bone growth was evaluated by radiography, histology, biochemistry, and mechanical testing after 8 wk. RESULTS: In bone defects, constructs implanted with cell sheets showed callus formation with segmental or continuous bone formation at 8 wk, in contrast to TCP seeded with BMSCs, which resulted in bone non-union. Wrapping TCP constructs with osteogenic matrix cell sheets increased their osteogenic potential and resulting bone formation, compared with conventional bone tissue engineering TCP scaffolds seeded with BMSCs. The compressive stiffness (mean +/- SD) values were 225.0 +/- 95.7, 30.0 +/- 11.5, and 26.3 +/- 10.6 MPa for BMSC/TCP/Sheet constructs with continuous bone formation, BMSC/TCP/Sheet constructs with segmental bone formation, and BMSC/TCP constructs, respectively. The compressive stiffness of BMSC/TCP/Sheet constructs with continuous bone formation was significantly higher than those with segmental bone formation and BMSC/TCP constructs. CONCLUSION: This technique is an improvement over current methods, such as TCP substitution, and is useful for hard tissue reconstruction and inducing earlier bone union in defects. PMID- 26131319 TI - New model for cardiomyocyte sheet transplantation using a virus-cell fusion technique. AB - AIM: To facilitate close contacts between transplanted cardiomyocytes and host skeletal muscle using cell fusion mediated by hemagglutinating virus of Japan envelope (HVJ-E) and tissue maceration. METHODS: Cardiomyocytes (1.5 * 10(6)) from fetal rats were first cultured. After proliferation, some cells were used for fusion with adult muscle fibers using HVJ-E. Other cells were used to create cardiomyocyte sheets (area: about 3.5 cm(2) including 2.1 * 10(6) cells), which were then treated with Nile blue, separated, and transplanted between the latissimus dorsi and intercostal muscles of adult rats with four combinations of HVJ-E and/or NaOH maceration: G1: HVJ-E(+), NaOH(+), Cardiomyocytes(+); G2: HVJ E(-), NaOH(+), Cardiomyocytes(+); G3: HVJ-E(+), NaOH(-), Cardiomyocytes(+); G4: HVJ-E(-), NaOH(-), Cardiomyocytes(-). At 1 and 2 wk after transplantation, the four groups were compared by detection of beating domains, motion images using moving target analysis software, action potentials, gene expression of MLC-2v and Mesp1 by reverse transcription-polymerase chain reaction, hematoxylin-eosin staining, and immunostaining for cardiac troponin and skeletal myosin. RESULTS: In vitro cardiomyocytes were fused with skeletal muscle fibers using HVJ-E. Cardiomyocyte sheets remained in the primary transplanted sites for 2 wk. Although beating domains were detected in G1, G2, and G3 rats, G1 rats prevailed in the number, size, motion image amplitudes, and action potential compared with G2 and G3 rats. Close contacts were only found in G1 rats. At 1 wk after transplantation, the cardiomyocyte sheets showed adhesion at various points to the myoblast layer in the latissimus dorsi muscle. At 2 wk after transplantation, close contacts were seen over a broad area. Part of the skeletal muscle sarcoplasma seemed to project into the myocardiocyte plasma and some nuclei appeared to share both sarcoplasmas. CONCLUSION: The present results show that close contacts were acquired and facilitated the beating function, thereby providing a new cellular transplantation method using HVJ-E and NaOH maceration. PMID- 26131320 TI - Incretin manipulation in diabetes management. AB - Incretin-based therapies have revolutionized the medical management of type 2 diabetes mellitus (T2DM) in the 21(st) century. Glucagon-like peptide-1 (GLP-1) suppresses appetite and gastric motility, and has trophic effects on pancreas, cardio-protective and renal effects. GLP-1 analogues and dipeptidyl peptidase-4 inhibitors form the incretin-based therapies. Significant reduction of hemoglobin A1c when used as monotherapy and in combination regimens, favorable effects on body weight, and low risk of hypoglycemia are their unique therapeutic benefits. Their safety and tolerability are comparable to other anti-diabetic medications. Concern about elevated risk of pancreatitis has been discarded by two recent meta analyses. This article discusses the therapeutic manipulation of incretin system for the management of T2DM. PMID- 26131321 TI - Gestational diabetes mellitus: An update on the current international diagnostic criteria. AB - The approach to screening and diagnosis of gestational diabetes mellitus (GDM) around the world is disorderly. The protocols for diagnosis vary not only in between countries, but also within countries. Furthermore, in any country, this disparity occurs in-between its hospitals and often exists within a single hospital. There are many reasons for these differences. There is the lack of an international consensus among preeminent health organizations (e.g., American College of Gynecologists and World Health Organization). Often there is a disagreement between the country's national diabetes organization, its local health society and its regional obstetric organization with each one recommending a different option for approaching GDM. Sometimes the causes for following an alternate approach are very obvious, e.g., a resource strapped hospital is unable to follow the ivory-tower demanding recommendation of its obstetric organization. But more often than not, the rationale for following or not following a guideline, or following different guideline within the same geographic area is without any perceivable explanation. This review is an attempt to understand the problems afflicting the screening and diagnosis of GDM globally. It traces the major temporal changes in the diagnostic criteria of (1) some respected health organizations; and (2) a few selected countries. With an understanding of the reasons for this disparity, a way forward can be found to reach the ultimate goal: a single global guideline for GDM followed worldwide. PMID- 26131322 TI - Diagnostic and prognostic utility of non-invasive imaging in diabetes management. AB - Medical imaging technologies are acquiring an increasing relevance to assist clinicians in diagnosis and to guide management and therapeutic treatment of patients, thanks to their non invasive and high resolution properties. Computed tomography, magnetic resonance imaging, and ultrasonography are the most used imaging modalities to provide detailed morphological reconstructions of tissues and organs. In addition, the use of contrast dyes or radionuclide-labeled tracers permits to get functional and quantitative information about tissue physiology and metabolism in normal and disease state. In recent years, the development of multimodal and hydrid imaging techniques is coming to be the new frontier of medical imaging for the possibility to overcome limitations of single modalities and to obtain physiological and pathophysiological measurements within an accurate anatomical framework. Moreover, the employment of molecular probes, such as ligands or antibodies, allows a selective in vivo targeting of biomolecules involved in specific cellular processes, so expanding the potentialities of imaging techniques for clinical and research applications. This review is aimed to give a survey of characteristics of main diagnostic non-invasive imaging techniques. Current clinical appliances and future perspectives of imaging in the diagnostic and prognostic assessment of diabetic complications affecting different organ systems will be particularly addressed. PMID- 26131324 TI - Enterovirus and type 1 diabetes: What is the matter? AB - A complex interaction of genetic and environmental factors can trigger the immune mediated mechanism responsible for type 1 diabetes mellitus (T1DM) establishment. Environmental factors may initiate and possibly sustain, accelerate, or retard damage to beta-cells. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of human enterovirus in the pathogenesis of T1DM. The genetic risk of T1DM and particular innate and acquired immune responses to enterovirus infection contribute to a tolerance to T1DM-related autoantigens. However, the frequency, mechanisms, and pathways of virally induced autoimmunity and beta-cell destruction in T1DM remain to be determined. It is difficult to investigate the role of enterovirus infection in T1DM because of several concomitant mechanisms by which the virus damages pancreatic beta-cells, which, consequently, may lead to T1DM establishment. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective. PMID- 26131323 TI - Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide. AB - Long-acting glucagon-like peptide-1 (GLP-1) analogues marketed for type 2 diabetes (T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors (GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions (e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase 4 degradation (thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2D, stroke and Alzheimer disease (AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential. PMID- 26131325 TI - Diabetes therapies in hemodialysis patients: Dipeptidase-4 inhibitors. AB - Although several previous studies have been published on the effects of dipeptidase-4 (DPP-4) inhibitors in diabetic hemodialysis (HD) patients, the findings have yet to be reviewed comprehensively. Eyesight failure caused by diabetic retinopathy and aging-related dementia make multiple daily insulin injections difficult for HD patients. Therefore, we reviewed the effects of DPP-4 inhibitors with a focus on oral antidiabetic drugs as a new treatment strategy in HD patients with diabetes. The following 7 DPP-4 inhibitors are available worldwide: sitagliptin, vildagliptin, alogliptin, linagliptin, teneligliptin, anagliptin, and saxagliptin. All of these are administered once daily with dose adjustments in HD patients. Four types of oral antidiabetic drugs can be administered for combination oral therapy with DPP-4 inhibitors, including sulfonylureas, meglitinide, thiazolidinediones, and alpha-glucosidase inhibitor. Nine studies examined the antidiabetic effects in HD patients. Treatments decreased hemoglobin A1c and glycated albumin levels by 0.3% to 1.3% and 1.7% to 4.9%, respectively. The efficacy of DPP-4 inhibitor treatment is high among HD patients, and no patients exhibited significant severe adverse effects such as hypoglycemia and liver dysfunction. DPP-4 inhibitors are key drugs in new treatment strategies for HD patients with diabetes and with limited choices for diabetes treatment. PMID- 26131328 TI - Alphabet Strategy for diabetes care: A multi-professional, evidence-based, outcome-directed approach to management. AB - With the rising global prevalence in diabetes, healthcare systems are facing a growing challenge to provide efficient and effective diabetes care management in the face of spiralling treatment costs. Diabetes is a major cause of premature mortality and associated with devastating complications especially if managed poorly. Although diabetes care is improving in England and Wales, recent audit data suggests care remains imperfect with wide geographical variations in quality. Diabetes care is expensive with a sizeable amount of available expenditure used for treating the complications of diabetes. A target driven, long-term, multifactorial intervention in patients with type 2 diabetes has been shown to reduce mortality and morbidity. The alphabet strategy is a novel approach to effective diabetes care provision, aiming to address patient education and empowerment, provide consistent comprehensive care delivered in a timely fashion, and allowing multidisciplinary team work. PMID- 26131327 TI - Effect of diabetes mellitus on sleep quality. AB - Diabetes mellitus (DM) is a highly prevalent condition affecting about 347 million people worldwide. In addition to its numerous clinical implications, DM also exerts a negative effect on patient's sleep quality. Impaired sleep quality disrupts the adequate glycemic control regarded as corner stone in DM management and also lead to many deleterious effects causing a profound impact on health related quality of life. This article outlines various factors leading to impaired sleep quality among diabetics and delineates how individual factor influences sleep. The article also discusses potential interventions and lifestyle changes to promote healthy sleep among diabetics. PMID- 26131329 TI - Pregnancy and neonatal outcomes in Indigenous Australians with diabetes in pregnancy. AB - AIM: To perform a systematic review of reported neonatal and pregnancy outcomes of Indigenous Australians with diabetes in pregnancy (DIP). METHODS: Electronic searches of PubMed and Web of Science were carried out. Articles were selected if they contained original data on DIP outcomes in Indigenous Australians. There were no specific exclusion criteria. RESULTS: A total of eight articles, predominantly from Queensland and Western Australia were identified once inclusion criteria were applied. Birth data from midwifery registries or paper charts encompassing years 1985-2008 were used. A total of 465591 pregnant women with and without DIP were included in the eight studies, with 1363 being Indigenous women with DIP. Indigenous Australians experienced increased rates of many known adverse outcomes of DIP including: macrosomia, caesarean section, congenital deformities, low birth weight, hypoglycaemia, and neonatal trauma. There were regional differences among Indigenous Australians, particularly regional/remote vs metropolitan populations where the regional/remote data showed worse outcomes. Two of the articles did not note a difference between Aboriginals and Caucasians in the rates of measured adverse outcome. Studies varied significantly in size, measured outcomes, and subsequent analysis. CONCLUSION: The health disparities between Indigenous Australians and non-Indigenous Australians are further evidenced by poorer outcomes in DIP. This has broader implications for Indigenous health in general. PMID- 26131326 TI - Diabetes mellitus: The epidemic of the century. AB - The epidemic nature of diabetes mellitus in different regions is reviewed. The Middle East and North Africa region has the highest prevalence of diabetes in adults (10.9%) whereas, the Western Pacific region has the highest number of adults diagnosed with diabetes and has countries with the highest prevalence of diabetes (37.5%). Different classes of diabetes mellitus, type 1, type 2, gestational diabetes and other types of diabetes mellitus are compared in terms of diagnostic criteria, etiology and genetics. The molecular genetics of diabetes received extensive attention in recent years by many prominent investigators and research groups in the biomedical field. A large array of mutations and single nucleotide polymorphisms in genes that play a role in the various steps and pathways involved in glucose metabolism and the development, control and function of pancreatic cells at various levels are reviewed. The major advances in the molecular understanding of diabetes in relation to the different types of diabetes in comparison to the previous understanding in this field are briefly reviewed here. Despite the accumulation of extensive data at the molecular and cellular levels, the mechanism of diabetes development and complications are still not fully understood. Definitely, more extensive research is needed in this field that will eventually reflect on the ultimate objective to improve diagnoses, therapy and minimize the chance of chronic complications development. PMID- 26131331 TI - Adenocarcinoma arising at ileostomy sites: Two cases and a review of the literature. AB - Total colectomy with ileostomy placement is a treatment for patients with inflammatory bowel disease or familial adenomatous polyposis (FAP). A rare and late complication of this treatment is carcinoma arising at the ileostomy site. We describe two such cases: a 78-year-old male 30 years after subtotal colectomy and ileostomy for FAP, and an 85-year-old male 50 years after colectomy and ileostomy for ulcerative colitis. The long latency period between creation of the ileostomies and development of carcinoma suggests a chronic metaplasia due to an irritating/inflammatory causative factor. Surgical excision of the mass and relocation of the stoma is the mainstay of therapy, with possible benefits from adjuvant chemotherapy. Newly developed lesions at stoma sites should be biopsied to rule out the possibility of this rare ileostomy complication. PMID- 26131330 TI - Intraoperative blood loss in orthotopic liver transplantation: The predictive factors. AB - Liver transplantation has been associated with massive blood loss and considerable transfusion requirements. Bleeding in orthotopic liver transplantation is multifactorial. Technical difficulties inherent to this complex surgical procedure and pre operative derangements of the primary and secondary coagulation system are thought to be the principal causes of perioperative hemorrhage. Intraoperative practices such as massive fluid resuscitation and resulting hypothermia and hypocalcemia secondary to citrate toxicity further aggravate the preexisting coagulopathy and worsen the perioperative bleeding. Excessive blood loss and transfusion during orthotopic liver transplant are correlated with diminished graft survival and increased septic episodes and prolonged ICU stay. With improvements in surgical skills, anesthetic technique, graft preservation, use of intraoperative cell savers and overall perioperative management, orthotopic liver transplant is now associated with decreased intra operative blood losses. The purpose of this review is to discuss the risk factors predictive of increased intra operative bleeding in patients undergoing orthotopic liver transplant. PMID- 26131332 TI - Gastrointestinal stromal tumour presenting as palpable abdominal mass: A rare entity. AB - Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumour of gastro-intestinal tract. Annual incidence of GIST in United States is approximately 3000-4000. Clinical presentation of GIST varies with location and size of tumour but GIST presenting with palpable abdominal mass is rare. We report a case of 38 years old male who presented with large abdominal lump. Computed tomography (CT) scan showed a large solid-cystic lesion encasing second part of duodenum and distal common bile duct. On CT differential diagnosis of Leiomyoma, Leiomyosarcoma and GIST were made. The diagnosis of GIST was confirmed by immune-histochemical study of the biopsy material. Patient underwent pancreaticodudenectomy. Post-operative course was uneventful. Patient was started on Imatinib therapy post-operatively. No recurrence noted at six months follow up. PMID- 26131333 TI - Left atrial physiology and pathophysiology: Role of deformation imaging. AB - The left atrium (LA) acts as a modulator of left ventricular (LV) filling. Although there is considerable evidence to support the use of LA maximum and minimum volumes for disease prediction, theoretical considerations and a growing body of literature suggest to focus on the quantification of the three basic LA functions: (1) Reservoir function: collection of pulmonary venous return during LV systole; (2) Conduit function: passage of blood to the left ventricle during early LV diastole; and (3) Contractile booster pump function (augmentation of ventricular filling during late LV diastole. Tremendous advances in our ability to non-invasively characterize all three elements of atrial function include speckle tracking echocardiography (STE), and more recently cardiovascular magnetic resonance myocardial feature tracking (CMR-FT). Corresponding imaging biomarkers are increasingly recognized to have incremental roles in determining prognosis and risk stratification in cardiac dysfunction of different origins. The current editorial introduces the role of STE and CMR-FT for the functional assessment of LA deformation as determined by strain and strain rate imaging and provides an outlook of how this exciting field may develop in the future. PMID- 26131334 TI - Perspective of future drugs targeting sterile 20/SPS1-related proline/alanine rich kinase for blood pressure control. AB - According to a genome-wide association study, intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes, mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge, phosphorylation of upstream with-no-lysine (K) (WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3 - Cullin 3 E3 ligase, hyperinsulinemia, and low potassium intake to mediate hypertension have been identified. In addition, the SPAK kinases may affect the action of renin angiotensin-aldosterone system on blood pressure as well. In 2010, two SPAK knock in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently, two novel SPAK inhibitors for mice, Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK (gene or kinase). PMID- 26131335 TI - Preliminary experience with drug-coated balloon angioplasty in primary percutaneous coronary intervention. AB - We evaluated the clinical feasibility of using drug-coated balloon (DCB) angioplasty in patients undergoing primary percutaneous coronary intervention (PPCI). Between January 2010 to September 2014, 89 ST-elevation myocardial infarction patients (83% male, mean age 59 +/- 14 years) with a total of 89 coronary lesions were treated with DCB during PPCI. Clinical outcomes are reported at 30 d follow-up. Left anterior descending artery was the most common target vessel for PCI (37%). Twenty-eight percent of the patients had underlying diabetes mellitus. Mean left ventricular ejection fraction was 44% +/- 11%. DCB only PCI was the predominant approach (96%) with the remaining 4% of patients receiving bail-out stenting. Thrombolysis in Myocardial Infarction (TIMI) 3 flow was successfully restored in 98% of patients. An average of 1.2 +/- 0.5 DCB were used per patient, with mean DCB diameter of 2.6 +/- 0.5 mm and average length of 23.2 +/- 10.2 mm. At 30-d follow-up, there were 4 deaths (4.5%). No patients experienced abrupt closure of the infarct-related artery and there was no reported target-lesion failure. Our preliminary experience showed that DCB angioplasty in PPCI was feasible and associated with a high rate of TIMI 3 flow and low 30-d ischaemic event. PMID- 26131336 TI - Nomenclature, categorization and usage of formulae to adjust QT interval for heart rate. AB - Assessment of the QT interval on a standard 12 lead electrocardiogram is of value in the recognition of a number of conditions. A critical part of its use is the adjustment for the effect of heart rate on QT interval. A systematic search was conducted to identify studies that proposed formulae to standardize the QT interval by heart rate. A nomenclature was developed for current and subsequent equations based on whether they are corrective (QTc) or predictive (QTp). QTc formulae attempt to separate the dependence of the length of the QT interval from the length of the RR interval. QTp formulae utilize heart rate and the output QTp is compared to the uncorrected QT interval. The nomenclature consists of the first letter of the first author's name followed by the next two consonance (whenever possible) in capital letters; with subscripts in lower case alphabetical letter if the first author develops more than one equation. The single exception was the Framingham equation, because this cohort has developed its own "name" amongst cardiovascular studies. Equations were further categorized according to whether they were linear, rational, exponential, logarithmic, or power based. Data show that a person's QT interval adjusted for heart rate can vary dramatically with the different QTc and QTp formulae depending on the person's heart rate and QT interval. The differences in the QT interval adjustment equations encompasses values that are considered normal or significant prolonged. To further compare the equations, we considered that the slope of QTc versus heart rate should be zero if there was no correlation between QT and heart rate. Reviewing a sample of 107 patient ECGs from a hospital setting, the rank order of the slope - from best (closest to zero) to worst was QTcDMT, QTcRTHa, QTcHDG, QTcGOT, QTcFRM, QTcFRD, QTcBZT and QTcMYD. For two recent formulae based on large data sets specifically QTcDMT and QTcRTHa, there was no significant deviation of the slope from zero. In summary a nomenclature permits easy reference to QT formulae that adjust for heart rate. Twenty different formulae can produce discordant calculations of an adjusted QT interval. While the formulae developed by Bazett and Fridericia (QTcBZT and QTcFRD respectively) may continue to be used clinically, recent formulae from large population studies specifically QTcDMT and QTcRTHa appear to be better to adjust QT for heart rate in clinical practice. PMID- 26131337 TI - Closing patent foramen ovale in cryptogenic stroke: The underscored importance of other interatrial shunt variants. AB - Recent trials and metanalysis even not fully conclusive and still debated, at least suggested that mechanical device-based closure of patent foramen ovale (PFO) is more effective than medical therapy in prevent recurrence of stroke. In a proportion ranging from 20% to nearly 40% of patients in literature, PFO is associated to atrial septal aneurysm (ASA): ASA is a well-known entity often associated with additional fenestration. Additionally small atrial septal defects ("Flat ASD") can present with signs of paradoxical embolism and cannot be easily detected by transthoracic echocardiography or even by transesophageal echocardiography and are usually discovered by intracardiac echocardiography at the moment of transcatheter closure. This evidence might change potentially the anatomical diagnosis from PFO to fenestrated ASA or as we called it to "hybrid defect", being a bidirectional flow through a small ASD or/and an additional fenestration, often present. Despite the differences in anatomy, pathophysiology and haemodynamic paradoxical embolism may occur in both entities and also may be the first appearance of fenestrated ASA. Because some overlapping do really exist between PFO and hybrid defects, which are often not clearly differentiable by standard diagnostic tools, it is likely that a proportion of patients evaluated for potential transcatheter closure of PFO had actually a different anatomical substrate. These different anatomical and pathophysiologic entities have not been address in any of the previous trials, potentially having an impact on overall results despite the similar mechanical treatment. Neurologists and general cardiologists in charge of clinical management of PFO-related cryptogenic stroke should be aware of the role of hybrid defects in the pathophysiology of paradoxical embolism - mediated cerebral ischemic events in order to apply the correct decision - making process and avoid downgrading of patients with paradoxical embolism-related interatrial shunt variants different from PFO. PMID- 26131338 TI - Bone morphogenetic protein-4 and transforming growth factor-beta1 mechanisms in acute valvular response to supra-physiologic hemodynamic stresses. AB - AIM: To explore ex vivo the role of bone morphogenetic protein-4 (BMP-4) and transforming growth factor-beta1 (TGF-beta1) in acute valvular response to fluid shear stress (FSS) abnormalities. METHODS: Porcine valve leaflets were subjected ex vivo to physiologic FSS, supra-physiologic FSS magnitude at normal frequency and supra-physiologic FSS frequency at normal magnitude for 48 h in a double sided cone-and-plate bioreactor filled with standard culture medium. The role of BMP-4 and TGF-beta1 in the valvular response was investigated by promoting or inhibiting the downstream action of those cytokines via culture medium supplementation with BMP-4 or the BMP antagonist noggin, and TGF-beta1 or the TGF beta1 inhibitor SB-431542, respectively. Fresh porcine leaflets were used as controls. Each experimental group consisted of six leaflet samples. Immunostaining and immunoblotting were performed to assess endothelial activation in terms of intercellular adhesion molecule-1 and vascular cell adhesion molecule 1 expressions, paracrine signaling in terms of BMP-4 and TGF-beta1 expressions and extracellular matrix (ECM) remodeling in terms of cathepsin L, cathepsin S, metalloproteinases (MMP)-2 and MMP-9 expressions. Immunostained images were quantified by normalizing the intensities of positively stained regions by the number of cells in each image while immunoblots were quantified by densitometry. RESULTS: Regardless of the culture medium, physiologic FSS maintained valvular homeostasis. Tissue exposure to supra-physiologic FSS magnitude in standard medium stimulated paracrine signaling (TGF-beta1: 467% +/- 22% vs 100% +/- 6% in fresh controls, BMP-4: 258% +/- 22% vs 100% +/- 4% in fresh controls; P < 0.05) and ECM degradation (MMP-2: 941% +/- 90% vs 100% +/- 19% in fresh controls, MMP 9: 1219% +/- 190% vs 100% +/- 16% in fresh controls, cathepsin L: 1187% +/- 175% vs 100% +/- 12% in fresh controls, cathepsin S: 603% +/- 88% vs 100% +/- 13% in fresh controls; P < 0.05), while BMP-4 supplementation also promoted fibrosa activation and TGF-beta1 inhibition reduced MMP-9 expression to the native tissue level (MMP-9: 308% +/- 153% with TGF-beta1 inhibition vs 100% +/- 16% in fresh control; P > 0.05). Supra-physiologic FSS frequency had no effect on endothelial activation and paracrine signaling regardless of the culture medium but TGF-beta1 silencing attenuated FSS-induced ECM degradation via MMP-9 downregulation (MMP-9: 302% +/- 182% vs 100% +/- 42% in fresh controls; P > 0.05). CONCLUSION: Valvular tissue is sensitive to FSS abnormalities. The TGF-beta1 inhibitor SB-431542 is a potential candidate molecule for attenuating the effects of FSS abnormalities on valvular remodeling. PMID- 26131339 TI - Utility of electrophysiological studies to predict arrhythmic events. AB - AIM: To evaluate the prognostic value of electrophysiological stimulation (EPS) in the risk stratification for tachyarrhythmic events and sudden cardiac death (SCD). METHODS: We conducted a prospective cohort study and analyzed the long term follow-up of 265 consecutive patients who underwent programmed ventricular stimulation at the Luzerner Kantonsspital (Lucerne, Switzerland) between October 2003 and April 2012. Patients underwent EPS for SCD risk evaluation because of structural or functional heart disease and/or electrical conduction abnormality and/or after syncope/cardiac arrest. EPS was considered abnormal, if a sustained ventricular tachycardia (VT) was inducible. The primary endpoint of the study was SCD or, in implanted patients, adequate ICD-activation. RESULTS: During EPS, sustained VT was induced in 125 patients (47.2%) and non-sustained VT in 60 patients (22.6%); in 80 patients (30.2%) no arrhythmia could be induced. In our cohort, 153 patients (57.7%) underwent ICD implantation after the EPS. During follow-up (mean duration 4.8 +/- 2.3 years), a primary endpoint event occurred in 49 patients (18.5%). The area under the receiver operating characteristic curve (AUROC) was 0.593 (95%CI: 0.515-0.670) for a left ventricular ejection fraction (LVEF) < 35% and 0.636 (95%CI: 0.563-0.709) for inducible sustained VT during EPS. The AUROC of EPS was higher in the subgroup of patients with LVEF >= 35% (0.681, 95%CI: 0.578-0.785). Cox regression analysis showed that both, sustained VT during EPS (HR: 2.26, 95%CI: 1.22-4.19, P = 0.009) and LVEF < 35% (HR: 2.00, 95%CI: 1.13-3.54, P = 0.018) were independent predictors of primary endpoint events. CONCLUSION: EPS provides a benefit in risk stratification for future tachyarrhythmic events and SCD and should especially be considered in patients with LVEF >= 35%. PMID- 26131340 TI - Giant saphenous vein graft pseudoaneurysm to right posterior descending artery presenting with superior vena cava syndrome. AB - Saphenous vein grafts (SVG) pseudoaneurysms, especially giant ones, are rare and occur as a late complication of coronary artery bypass grafting. This condition affects both genders and typically occurs within the sixth decade of life. The clinical presentation ranges from an asymptomatic incidental finding on imaging studies to new onset angina, dyspnea, myocardial infarction or symptoms related to compression of neighboring structures. An 82-year-old woman presented with acute onset back pain, dyspnea and was noted to have significantly engorged neck veins. In the emergency department, a chest computed tomographic angiogram with intravenous contrast revealed a ruptured giant bilobed SVG pseudoaneurysm to the right posterior descending artery (RPDA). This imaging modality also demonstrated compression of the superior vena cava (SVC) by the SVG pseudoaneurysm. Coronary angiogram with bypass study was performed to establish the patency of this graft. Endovascular coiling and embolization of the SVG to RPDA was initially considered but disfavored after the coronary angiogram revealed preserved flow from the graft to this arterial branch. After reviewing the angiogram films, a surgical strategy was favored over a percutaneous intervention with a Nitinol self expanding stent since the latter would have not addressed the superior vena cava compression caused by the giant pseudoaneurysm. Intraoperative transesophageal echocardiogram demonstrated SVC compression by the giant pseudoaneurysm cranial lobe. Our patient underwent surgical ligation and excision of the giant pseudoaneurysm and the RPDA was regrafted successfully. In summary, saphenous vein grafts pseudoaneurysms can be life-threatening and its therapy should be guided based on the presence of mechanical complications, the patency of the affected vein graft and the involved myocardial territory viability. PMID- 26131341 TI - Long term evolution of magnetic resonance imaging characteristics in a case of atypical left lateral wall hypertrophic cardiomyopathy. AB - We are reporting a long-time magnetic resonance imaging (MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance (CMR) imaging can be a valuable tool for assessment of detailed information on size, localization, and tissue characteristics of hypertrophied myocardium. However, there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently, our group reported a case of left lateral wall HCM as a rare variant of the more common forms, such as septal HCM, or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago, we are able to provide the thrilling experience of an ultra-long MRI follow-up presentation in this rare case of left lateral wall hypertrophy. Furthermore, this case outlines the tremendous improvements in imaging quality within the last two decades of CMR imaging. PMID- 26131342 TI - Reverse or inverted apical ballooning in a case of refeeding syndrome. AB - Takotsubo cardiomyopathy is characterized by the development of transient left ventricular regional wall motion abnormalities, in the absence of significant coronary artery obstruction. This syndrome usually occurs in women and is frequently associated with an intense emotional or physical stress. It usually involves apical segments, but in the recent years atypical forms have been described. Inverted or reverse Takotsubo is a variant in which the basal and midventricular segments are hypokinetic, sparing contractile function of the apex. In this report we describe the case of a 54-year-old woman, with chronic malnutrition, initially admitted because of hypoglycemia and severe electrolyte disturbance due to a refeeding syndrome. Within the next hours she experienced acute cardiac symptoms and developed heart failure with low cardiac output. Electrocardiogram (ECG), elevation of troponin and echocardiographic findings were consistent with inverted Takotsubo cardiomyopathy. To the best of our knowledge, this is the first incidence reported of inverted Takotsubo triggered by refeeding syndrome. PMID- 26131343 TI - Case of angina pectoris at rest and during effort due to coronary spasm and myocardial bridging. AB - We present a case of a 71-year-old male who had chest symptoms at rest and during effort. He had felt chest oppression during effort for 1 year, and his chest symptoms had recently worsened. One month before admission he felt chest squeezing at rest in the early morning. He presented at our institution to evaluate his chest symptoms. Electrocardiography and echocardiography failed to show any specific changes. Because of the possibility that his chest symptoms were due to myocardial ischemia, he was admitted to our institution for coronary angiography (CAG). An initial CAG showed mild atherosclerotic changes in the proximal segment of the left anterior descending coronary artery (LAD) and mid segment of the left circumflex coronary artery. Subsequent spasm provocation testing using acetylcholine revealed a bilateral coronary vasospasm, which was relieved after the intracoronary infusion of nitroglycerin. Finally, a CAG showed myocardial bridging (MB) of the mid-distal segments of the LAD. Fractional flow reserve using the intravenous administration of adenosine triphosphate was positive at 0.77, which jumped up to 0.90 through the myocardial bridging segments when the pressure wire was pulled back. Thus, coronary vasospasm and MB might have contributed to his chest symptoms at rest and during effort. Interventional cardiologists should consider the presence of MB as a potential cause of myocardial ischemia. PMID- 26131344 TI - Association between height and malignancy among children in the north of Iran. AB - BACKGROUND: This study aim to determine the association between height and cancer in the children aged 14 years at the time of diagnosis in Rasht, Iran. MATERIALS AND METHODS: In this cross-sectional study, height of patients with a malignancy (<=14) at the time of diagnosis measured in the standard charts of United States National Center for the Health Statistics (NCHS). Data were reported by descriptive statistics and analyzed by Regression tests in SPSS version 19. RESULTS: Overall, 78 male (38.6%) and 124 female (61.4%) patients with various kinds of malignancies were evaluated for their heights. Leukemia was the most common type of cancer. The median height of the patients was more than 20(th) percentile and under 50(th) percentile of the NCHS. No significant association was found between height and leukemia. CONCLUSION: Previously, the median height of Iranian girls and boys (<=15) reported under 20(th) percentile of the NCHS. In this study, the median height of the patients at the time of diagnosis was more than 20(th) percentile of the NCHS. There was a correlation between height and cancer among our patients, although, this correlation can be assessed by further cohort study. PMID- 26131345 TI - Prevalence of Psychiatric Symptoms in ALL Patients during Maintenance Therapy. AB - BACKGROUND: Cancer diagnosis may cause deep emotional and affective problems in patients and their families. Nowadays, however, despite its rising prevalence, cancer is no longer synonymous with death. Given the significance of emotional well-being in cancer patients, we decided to assess the frequency of psychological problems in seven to seventeen year-olds with acute lymphoblastic leukemia. MATERIALS AND METHODS: Our sample included 42 children and adolescents with ALL referred to pediatric hematology department of Dr. Sheikh hospital, who were put under maintenance course of the treatment. Psychiatric disorders such as anxiety, depression and behavioral disturbances were examined by using RCMAS, CDI and SDQ questionnaires respectively. RESULTS: The entire population showed depressive symptoms.59.5% of patients (25 person) suffered from anxiety and 26.2% (11 person) had behavioral problems. No significant relation was found between depressive symptoms, and age (p=0.77), sex (p=0.97), length of disease (p=0.50), and type of treatment (p=0.064). Anxiety did not show any significant relation with age (p= 0.63), sex (p= 0.32), length of disease (p= 0.16) and treatment type (p= 0.064).Similarly behavioral disturbances did not indicate any suggestive relation with age (p= 0.20), sex (p= 0.56), length of disease (p= 0.81) and type of treatment (p= 0.19). CONCLUSION: Our findings suggest a high prevalence of psychiatric disorders in children and adolescents with ALL. It is strongly recommended, therefore, that besides somatic symptoms, careful attention be paid to psychological disorders. This can prevent rapid development of the disease reduce treatment costs, and improve the quality of life for both patients and their families. PMID- 26131346 TI - Association between serum ferritin level and diastolic cardiac function in patients with major beta-thalassemia. AB - BACKGROUND: Prevention of myocardial siderosis is a key step to reduce rate of mortality in thalassemic patients. Our objective was to study association between echocardiography parameters and serum ferritin level in patients with major thalassemia. MATERIALS AND METHODS: Sixty-six patients with major thalassemia were studied in Amir Kabir hospital, Arak, Iran. Serum ferritin levels were measured during 3 months in patients with no symptoms of infection. It was measured by enzyme-linked immunosorbent assay (ELISA). Ejection Fraction (EF), Fractional Shortening (FS) and Early/Late ratio (E/A) were studied by echocardiography. RESULTS: Fifty two percent were female and 48% were male. Mean age was 16 +/- 9 years and the age range was3-26years. Mean serum ferritin level was1912 +/- 1748 ng/dl and its range was from 303 to 8333 ng/dl. There were significant correlations between serum ferritin level and EF(r=0.3 and P=0.05) and also between serum ferritin level and FS. CONCLUSION: Due to significant association between serum ferritin level and echo parameters, it is beneficial that all patients with major thalassemia undergo echocardiography to gain better understating about cardiac function. PMID- 26131347 TI - Comparison of hematological aspects among children with Malaria and healthy children. AB - BACKGROUND: Malaria is an acute and chronic illness characterized by paroxysms of fever, chills, sweating, fatigue, anemia, and splenomegaly. Most malarial deaths occur in infants and young children.Anemia in malaria has diverse pathophysiologic mechanisms such as direct invasion of Red cells, In the following, we presented comparison of hematological aspects: children with Malaria and healthy children. MATERIALS AND METHODS: This was a lab trial study. Patients were referred and admitted to the pathobiology laboratory along with physical examination. Then, they underwent a complete blood count and the result of complete blood count was compared with healthy person in the same age. Out of 30 patients, with equally falciparum, vivax, and healthy .The hematological examination was performed. Finally, the data was analyzed using SPSS version 19 software. RESULTS: The levels of HGB (P=0.001), HCT (P=0.001), MCV (P= 0.001), MCH (P=0.001), WBC (P=0.001), and Plt (P= 0.02) decreased significantly in children with falciparum and vivax malaria compared to healthy controls. The levels of RBC (P=0.49) increased significantly in children with falciparum and vivax malaria compared to controls. Blood culture at two times. To investigate malaria; blood smears taken after microscopic study of Plasmodium falciparum ring was observed. CONCLUSION: Malaria is a multisystem disorder which can lead to many diseases. Physicians, especially those in endemic areas, should be aware of the varied manifestations and maintain in a high index of suspicion for the disease in order to that diagnose and treat timely and, morbidity and mortality. PMID- 26131348 TI - Prevalence and specificities of red cell alloantibodies in transfusion-dependent beta thalassemia patients in Yazd. AB - BACKGROUND: Multiple transfusions in thalassemia patients may lead to antibody production against blood group antigens and hemolytic transfusion reaction might occur. In this study, antibody screening test was performed by tube and gel methods to determine the prevalence and specificity of alloantibodies in thalassemia patients. MATERIALS AND METHODS: In this cross-sectional study, overall of 100 thalassemia patients from Yazd thalassemia clinic were recruited from July to September 2013. Two blood samples with volume of 6 ml were collected from each patient for standard tube and gel method antibody screening tests and a questionnaire consisting of demographic, health and blood transfusion status was completed. RESULTS: Out of 100 cases, 54 were female (54%) and 46 male (46%). The patients' age mean was 14.97+/-7.91 years with 2 to 33 years age range. Only 4% (n=4) had developed alloantibodies. (One patient developed dual alloantibody (Anti-C and Anti-D) and three patients developed single alloantibody (Anti K)).Gel method detected 4 patients with alloantibody but in two patients not detected by the standard tube method. CONCLUSION: The prevalence of RBC alloantibody production in this study was less than most previous studies. Anti-K was the most prevalent alloantibody in thalassemia patients in Yazd. It seems Rh and Kell blood group phenotyping in a newly diagnosed thalassemia patient and selection of matched blood for transfusion is very important. PMID- 26131349 TI - Awareness and performance of blood transfusion standards in operating rooms of Shiraz hospitals in 2012. AB - BACKGROUND: Assuring safety and survival of blood in vitro depends on anti coagulation substances, blood bag characteristics, storage conditions, and transport of blood. Besides, careful selection and screening of donors as well as blood tests can minimize the transmission risk of blood-transmissible pathogens and optimize blood health. The aim of this study was to assay the level of knowledge and practices among anesthesia technicians on blood transfusion standards. MATERIALS AND METHODS: This descriptive cross-sectional study was performed among 85 anesthesia technicians Shiraz, Iran throughout 2012 who were examined by census using blood transfusion questionnaires and checklists. The data were analyzed using SPSS 16 software. RESULTS: The obtained findings indicated that 32.44% of the technicians have corrected knowledge of blood transfusion standards; nevertheless, 73.84% have corrected performance. CONCLUSIONS: The technicians mostly performed based on their habit and experience. However, their knowledge about blood transfusion and blood bag storage was low. PMID- 26131351 TI - Successful Management of Vinblastin Overdose with Exchange Transfusion: A Case Report. AB - Accidental overdose of chemotherapy drugs including vinblastin (VBL) have been reported in the literature. As VBL overdose is potentially fatal, we decided to introduce a 2-year-old girl affected by langerhans' cell histiocytosis who was accidentally injected 10-times the prescribed dose of VBL (16 mg), and was saved with whole blood double exchange transfusion at 8 and 20 hrs after the accidental injection. The earliest manifestations were irritability and sinus tachycardia which alleviated after starting digoxin and at the end of the 2(nd) exchange transfusion. Other reported adverse effects were myelosuppression, weakness of extremities, diminished deep tendon reflexes and ileus which resolved at the time of discharge from hospital on day 13 of admission. It is speculated that exchange transfusion is an effective modality in reducing the serious adverse effects of VBL overdose. PMID- 26131350 TI - Mouth-rinses for the prevention of chemotherapy induced oral mucositis in children: a systematic review. AB - BACKGROUND: The purpose of this review was to evaluate studies in basic oral care interventions to update evidence based practice guidelines for preventing oral mucositis (OM) in cancer patients undergoing chemotherapy. MATERIAL & METHODS: Pub Med database and Google Scholar were searched for all papers published between 2000 and December 2014 in English that were conducted using the search terms including ''mocusitis, chemotherapy, mouth-rinses, oral care, oral care protocol, dental care,dental cleaning, oral decontamination, oral hygiene", and the combined phrases in order to obtain all relevant studies. RESULTS: The initial search concluded 151 published papers representing both research and clinical work. Review articles, clinical case reports, literature reviews, and other nonresearch articles were excluded from the review. Following this process, 30 papers remained. CONCLUSION: Among these, chlorhexidine, normal saline, sodium bicarbonate, iseganan, benzydamine, sucralfate and Granulocyte macrophage colony stimulating factor have been used in the form of mouth-rinse for prevention of chemotherapy induced mucositis. However, none of these mouthrinses have been shown to be definitely effective in preventing chemotherapy induced oral mucositis. PMID- 26131352 TI - Ambiguity and variability of database and software names in bioinformatics. AB - BACKGROUND: There are numerous options available to achieve various tasks in bioinformatics, but until recently, there were no tools that could systematically identify mentions of databases and tools within the literature. In this paper we explore the variability and ambiguity of database and software name mentions and compare dictionary and machine learning approaches to their identification. RESULTS: Through the development and analysis of a corpus of 60 full-text documents manually annotated at the mention level, we report high variability and ambiguity in database and software mentions. On a test set of 25 full-text documents, a baseline dictionary look-up achieved an F-score of 46 %, highlighting not only variability and ambiguity but also the extensive number of new resources introduced. A machine learning approach achieved an F-score of 63 % (with precision of 74 %) and 70 % (with precision of 83 %) for strict and lenient matching respectively. We characterise the issues with various mention types and propose potential ways of capturing additional database and software mentions in the literature. CONCLUSIONS: Our analyses show that identification of mentions of databases and tools is a challenging task that cannot be achieved by relying on current manually-curated resource repositories. Although machine learning shows improvement and promise (primarily in precision), more contextual information needs to be taken into account to achieve a good degree of accuracy. PMID- 26131353 TI - Exogenous 17-beta estradiol administration blunts progression of established angiotensin II-induced abdominal aortic aneurysms in female ovariectomized mice. AB - BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-beta estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice. METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr (-/-) mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx with E2 administration for 2 months of continued AngII infusions. Aortic lumen diameters were quantified by ultrasound and analyzed by linear mixed model, and maximal AAA diameters were analyzed by one-way ANOVA. Atherosclerosis was quantified en face in the aortic arch. AAA tissue sections were analyzed for cellular composition. We quantified effects of E2 on abdominal aortic smooth muscle cell (SMC) growth, alpha-actin and transforming growth factor-beta (TGF-beta) production, and wound healing. RESULTS: Serum E2 concentrations were increased significantly by E2. Aortic lumen diameters increased over time in sham-operated and Ovx (vehicle) females, but not in Ovx females administered E2. At day 70, E2 administration decreased significantly aortic lumen diameters compared to Ovx vehicle and sham-operated females. Compared to Ovx females (vehicle), maximal AAA diameters were reduced significantly by E2. AAA tissue sections from Ovx females administered E2 exhibited significant increases in alpha-actin and decreases in neutrophils compared to Ovx females administered vehicle. In abdominal aortic SMCs, E2 resulted in a concentration-dependent increase in alpha-actin, elevated TGF-beta, and more rapid wound healing. E2 administration to Ovx females also significantly reduced atherosclerotic lesions compared to sham-operated females. This effect was accompanied by significant reductions in serum cholesterol concentrations. CONCLUSIONS: E2 administration to Ovx females abolished progressive growth and decreased severity of AngII-induced AAAs. These effects were accompanied by increased SMC alpha-actin, elevated TGF-beta, and reduced neutrophils. Similarly, E2 administration reduced AngII-induced atherosclerosis. These results suggest that loss of E2 in post-menopausal females may contribute to progressive growth of AAAs. PMID- 26131355 TI - In conversation with...John Wendell Severinghaus. PMID- 26131354 TI - Peli1 negatively regulates type I interferon induction and antiviral immunity in the CNS. AB - BACKGROUND: Type I interferons (IFN-Is) serve as mediators of antiviral innate immunity and also regulate adaptive immune responses. The molecular mechanism that regulates virus-induced IFN-I production, particularly in tissue-resident immune cells, is incompletely understood. RESULTS: Here we identified the E3 ubiquitin ligase Peli1 as a negative regulator of IFN-I induction in microglia, innate immune cells of the central nervous system (CNS). Peli1 deficiency profoundly promoted IFN-beta expression in microglia in response to in vitro stimulation by toll-like receptor (TLR) ligands or a CNS-tropic virus, the vascular stomatitis virus (VSV). Upon intranasal infection with VSV, the Peli1 deficient mice displayed heightened in vivo IFN-I responses in the CNS, coupled with reduced brain viral titer and increased survival rate. CONCLUSIONS: These results establish Peli1 as an innate immune regulator in the CNS that modulates the threshold of IFN-I responses against viral infections. PMID- 26131356 TI - Alteration of Type I collagen microstructure induced by estrogen depletion can be prevented with drug treatment. AB - Two independent biological replicates of estrogen depletion were employed with differing drug treatment conditions. Data Set I consisted of 9-month-old New Zealand white female rabbits treated as follows: sham-operated (n=11), ovariectomized (OVX; n=12), OVX+200 MUg kg(-1) alendronate (ALN), 3 * a week for 27 weeks (n=12) and OVX+10 mg kg(-1) Cathepsin-K inhibitor (CatKI) daily for 27 weeks. Data Set II consisted of 6-month-old New Zealand white female rabbits that were sham-operated (n=12), OVX (n=12) or OVX+0.05 mg kg(-1) 17beta-estradiol (ERT) 3 * a week for 13 weeks (n=12). Samples from the cortical femur were polished and demineralized to make them suitable for atomic force microscopy (AFM) imaging. Type I collagen fibrils present in bundles or sheets, running parallel to each other, were combined into a class termed Parallel. Fibrils present outside of such structures, typically in images with an angular range of non-parallel fibrils, were combined into a class termed Oblique. The percentage of fibrils coded as Parallel for Sham animals in Data Sets I and II was 52% and 53%, respectively. The percentage of fibrils coded as Parallel for OVX animals in Data Sets I and II was 35% in both cases. ALN and ERT drug treatments reduced the change from 18 to 12%, whereas CatKI treatment reduced the change to 5%. PMID- 26131357 TI - Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity. AB - Phosphate homeostasis is coordinated and regulated by complex cross-organ talk through delicate hormonal networks. Parathyroid hormone (PTH), secreted in response to low serum calcium, has an important role in maintaining phosphate homeostasis by influencing renal synthesis of 1,25-dihydroxyvitamin D, thereby increasing intestinal phosphate absorption. Moreover, PTH can increase phosphate efflux from bone and contribute to renal phosphate homeostasis through phosphaturic effects. In addition, PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), which is able to inhibit renal tubular phosphate reabsorption, thereby increasing urinary phosphate excretion. FGF23 can also fine-tune vitamin D homeostasis by suppressing renal expression of 1-alpha hydroxylase (1alpha(OH)ase). This review briefly discusses how FGF23, by forming a bone-kidney axis, regulates phosphate homeostasis, and how its dysregulation can lead to phosphate toxicity that induces widespread tissue injury. We also provide evidence to explain how phosphate toxicity related to dietary phosphorus overload may facilitate incidence of noncommunicable diseases including kidney disease, cardiovascular disease, cancers and skeletal disorders. PMID- 26131359 TI - Cancer-targeted therapies and radiopharmaceuticals. AB - The treatment of bone metastases remains a clinical challenge. Although a number of well-established agents, namely bisphosphonates and denosumab, are available to reduce the occurrence of skeletal-related events, additional cancer-targeted therapies are required to improve patients' prognosis and quality of life. This review focuses on novel targets and agents that are under clinical evaluation for the treatment of malignant bone diseases such as activin A, src and endothelin-1 inhibition or agents that are clinically approved and may positively influence bone, such as the mTOR inhibitor everolimus. In addition, the potential of alpharadin, a novel radiopharmaceutical approved for the treatment of prostatic bone disease, is discussed. PMID- 26131358 TI - Inflammation and skeletal metastasis. AB - On the road to metastasis a cancer cell has to overcome two major obstacles: the physical escape from the primary tumor to a distant tissue and the adaptation to the new microenvironment via colonization and the formation of a secondary tumor. Accumulated scientific findings support the hypothesis that inflammation is a critical component of the tumor microenvironment and develops as a result of tumor-induced recruitment of inflammatory cells and their reciprocal interaction with other cells from the tumor network. These interactions modulate immune responses to suppress antitumor immunity and activate feedback amplification signaling loops that link nearly all the cells in the cancer inflammatory milieu. The coordinated regulation of cytokines/chemokines, receptors and other inflammatory mediators enables the different steps of the metastatic cascade. As a target organ for colonization, the bone is rich in inflammatory mediators that are critical for successful cancer growth. In this review, we focus on the inflammatory cells, molecules and mechanisms that facilitate the expansion of cancer cells from the primary tumor to their new 'home' in the skeleton. PMID- 26131360 TI - Determinants of hypercalcemia and hypercalciuria in immobilized trauma patients. AB - Hypercalcemia and hypercalciuria secondary to immobilization can be occasionally severe, producing an array of symptoms. This study looked at possible determinants of hypercalcemia and hypercalciuria in immobilized trauma patients. This is a prospective observational study carried out over a period of 7 months. Fifty-five immobilized trauma patients were evaluated weekly for 4 weeks for symptoms of hypercalcemia, total serum calcium and 24-h urinary calcium. The number of limbs immobilized had a significant relationship with hypercalcemia at the end of week 1 (P<0.001) and week 4 (P=0.008) and with hypercalciuria at the end of week 1 only (P<0.001). The number of bones fractured also had a significant relationship with hypercalcemia at the end of week 1 (P=0.005) and week 4 (P=0.019), as well as with hypercalciuria at the end of week 1 (P<0.001) and week 2 (P=0.036). Weight loss was significantly associated with hypercalcemia at the end of week 4 (P=0.014) and with hypercalciuria at the end of week 3 (P<0.001) and week 4 (P<0.001), whereas polyuria and polydipsia had a significant association with hypercalciuria at the end of week 2 (P<0.001) and week 3 (P=0.030). The number of limbs immobilized and bones fractured showed an early significant relationship with the development of hypercalcemia and hypercalciuria. Weight loss showed late association with hypercalcemia and hypercalciuria, whereas polyuria and polydipsia showed early association with hypercalciuria. PMID- 26131361 TI - Focus on the p38 MAPK signaling pathway in bone development and maintenance. AB - The p38 mitogen-activated protein kinase (MAPK) signaling pathway can be activated in response to a wide range of extracellular signals. As a consequence, it can generate many different biological effects that depend on the stimulus and on the activated cell type. Therefore, this pathway has been found to regulate many aspects of tissue development and homeostasis. Recent work with the aid of genetically modified mice has highlighted the physiological functions of this pathway in skeletogenesis and postnatal bone maintenance. In this review, emphasis is given to the roles of the p38 MAPK pathway in chondrocyte, osteoblast and osteoclast biology. In particular, we describe the molecular mechanisms of p38 MAPK activation and downstream targets. The requirement of this pathway in physiological bone development and homeostasis is demonstrated by the ability of p38 MAPK to regulate master transcription factors controlling geneses and functions of chondrocytes, osteoblasts and osteoclasts. PMID- 26131362 TI - In vivo reference point indentation measurement variability in skeletally mature inbred mice. AB - Reference point indentation (RPI) was developed to measure material-level mechanical properties of bone in vivo. Studies using RPI in vivo have discriminated between human subjects with previous skeletal fractures and those without and among dogs given different anti-remodeling drugs. Recently, this technology was extended to rats, providing the first in vivo data for rodents. The goal of the present study was to perform in vivo RPI measurements in mice, the most common animal model used to study bone. Twelve 16-week-old female C57BL/6 mice were subjected to RPI (three tests) on the anterior tibia, followed by a repeat test session on the contralateral limb 28 days later. A custom MATLAB program was used to derive several outcome parameters from RPI force-displacement curves: first cycle indentation distance (ID-1st), ID increase (IDI), total ID (TID), first cycle unloading slope (US-1st) and first cycle energy dissipation (ED-1st). Data within an individual were averaged across the three tests for each time point. Within-animal variation of all RPI parameters on day 1 ranged from 12.8 to 33.4% and from 14.1 to 22.4% on day 28. Between-animal variation on day 1 ranged from 11.4% to 22.8% and from 7.5% to 24.7% on day 28. At both time points, within- and between-animals, US-1st was the least variable parameter and IDI was most variable. All parameters were nonsignificantly lower at day 28 compared with day 1. These data are important to demonstrate the feasibility of collecting bone material property data longitudinally in mice and will inform the design of future studies in terms of statistical power and appropriate sample size considerations. PMID- 26131364 TI - Erratum: Epstein-Barr virus vaccines. AB - [This corrects the article DOI: 10.1038/cti.2014.27.]. PMID- 26131363 TI - Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review. AB - Androgen-deprivation therapy (ADT) has become a standard of care in the management of advanced prostate cancer or as an adjunct therapy. However, ADT is associated with a well-known deleterious effect on bone health, resulting in a decrease in bone-mass density (BMD) and increased risk for fracture. With the longer life expectancy of prostate cancer patients, improvement of the quality of life has become increasingly important. Therefore, adequate screening, prevention and treatment of BMD loss is paramount. Zoledronic acid and denosumab have shown promising results in recent studies, which has led to the Food and Drug Administration approval of these treatment options in various settings throughout the course of the disease, including the prevention of ADT-associated bone loss. This review focuses on the various parameters that impact BMD loss in men initiating ADT, on the specific effect of ADT on bone health and on various lifestyle modifications and treatment options such as bisphosphonates, osteoclast targeted therapy and selective estrogen-receptor modulators that have shown promising results in recent studies. PMID- 26131365 TI - A GMCSF and IL7 fusion cytokine leads to functional thymic-dependent T-cell regeneration in age-associated immune deficiency. AB - The competence of cellular immunity depends on a diverse T-cell receptor (TCR) repertoire arising from thymic output. Normal thymopoiesis arises from marrow derived CD3(-)CD4(-)CD8(-) triple-negative T-cell progenitors (TN), which develop into mature single-positive (SP) CD4 or CD8 T cells after expressing both CD4 and CD8 (double-positive, DP) transiently, leading to de novo T-cell production. Interleukin-7 (IL7) is a singularly important common gamma-chain IL involved in normal thymic development. Our previous work has demonstrated that gammac cytokines fused with granulocyte-macrophage colony stimulating factor (GMCSF) at the N-terminus acquire unheralded biological properties. Therefore, to enhance thymopoiesis, we developed a novel biopharmaceutical based on the fusion of GMCSF and IL7, hereafter GIFT7. Systemic administration of GIFT7 leads to cortical thymic hyperplasia including the specific expansion of CD44(int)CD25(-) double negative 1 (DN1) thymic progenitors. During murine cytomegalovirus (mCMV) infection of aged animals, GIFT7-mediated neo-thymopoiesis led to increased absolute numbers of viral-specific CD8(+) T cell. Our work demonstrated that thymic precursors can be therapeutically repopulated and its reconstitution leads to meaningful central and peripheral T-cell neogenesis, correcting immune dysfunction arising from age-associated thymic atrophy. PMID- 26131366 TI - The NEIL Memory Research Unit: psychosocial, biological, physiological and lifestyle factors associated with healthy ageing: study protocol. AB - BACKGROUND: Population ageing is a global phenomenon that has characterised demographic trends during the 20th and 21st century. The rapid growth in the proportion of older adults in the population, and resultant increase in the incidence of age-related cognitive decline, dementia and Alzheimer's disease, brings significant social, economic and healthcare challenges. Decline in cognitive abilities represents the most profound threat to active and healthy ageing. Current evidence suggests that a significant proportion of cases of age related cognitive decline and dementia may be preventable through the modification of risk factors including education, depressive symptomology, physical activity, social engagement and participation in cognitively stimulating activities. The NEIL Memory Research Unit cohort study was established to investigate factors related to brain health and the maintenance of cognitive function. METHODS: A cohort of 1000 normally ageing adults aged 50 years and over are being recruited to participate in comprehensive assessments at baseline, and at follow-up once every 2 years. The assessment protocol comprises a comprehensive neuropsychological battery, some basic physical measures, psychosocial scales, questionnaire measures related to a range of health, lifestyle and behavioural factors, and a measure of resting state activity using electroencephalography (EEG). DISCUSSION: The NEIL Memory Research Unit cohort study will address key questions about brain health and cognitive ageing in the population aged 50+, with a particular emphasis on the influence of potentially modifiable factors on cognitive outcomes. Analyses will be conducted with a focus on factors involved in the maintenance of cognitive function among older adults, and therefore will have the potential to contribute significant knowledge related to key questions within the field of cognitive ageing, and to inform the development of public health interventions aimed at preventing cognitive decline and promoting active and healthy ageing. PMID- 26131367 TI - A clear 'wake-up call' from Korea. PMID- 26131368 TI - Early radiographic diagnosis of peri-implantitis enhances the outcome of peri implantitis treatment: a 5-year retrospective study after non-surgical treatment. AB - PURPOSE: This retrospective study evaluated the relationship between the timing of peri-implantitis diagnosis and marginal bone level after a 5-year follow-up of non-surgical peri-implantitis treatment. METHODS: Thirty-three patients (69 implants) were given peri-implantitis diagnosis in 2008-2009 in Seoul National University Bundang Hospital. Among them, 31 implants from 16 patients were included in this study. They were treated non-surgically in this hospital, and came for regular maintenance visits for at least 5 years after peri-implantitis treatment. Radiographic marginal bone levels at each interval were measured and statistical analysis was performed. RESULTS: Timing of peri-implantitis was one of the significant factors affecting initial bone loss and total bone loss not additional bone after peri-implantitis diagnosis. Patients with cardiovascular disease and diabetic mellitus were positively influenced on both initial bone loss and total bone loss. Patients who needed periodontal treatment after implant placement showed a negative effect on bone loss compared to those who needed periodontal treatment before implant placement during entire periods. Implant location also significantly influenced on amounts of bone loss. Mandibular implants showed less bone loss than maxillary implants. Among surgical factors, combined use of autogenous and xenogenic bone graft materials showed a negative effect on bone loss compared to autogenous bone graft materials. Use of membrane negatively affected on initial bone loss but positively on additional bone loss and total bone loss. Thread exposure showed positive effects on initial bone loss and total bone loss. CONCLUSIONS: Early peri-implantitis diagnosis led to early non-surgical intervention for peri-implantitis treatment, which resulted in the maintenance of the bone level as well as preservation of the implant. PMID- 26131369 TI - In vivo comparison between the effects of chemically modified hydrophilic and anodically oxidized titanium surfaces on initial bone healing. AB - PURPOSE: The aim of this study was to investigate the combined effects of physical and chemical surface factors on in vivo bone responses by comparing chemically modified hydrophilic sandblasted, large-grit, acid-etched (modSLA) and anodically oxidized hydrophobic implant surfaces. METHODS: Five modSLA implants and five anodized implants were inserted into the tibiae of five New Zealand white rabbits (one implant for each tibia). The characteristics of each surface were determined using field emission scanning electron microscopy, energy dispersive spectroscopy, and confocal laser scanning microscopy before the installation. The experimental animals were sacrificed after 1 week of healing and histologic slides were prepared from the implant-tibial bone blocks removed from the animals. Histomorphometric analyses were performed on the light microscopic images, and bone-to-implant contact (BIC) and bone area (BA) ratios were measured. Nonparametric comparison tests were applied to find any significant differences (P<0.05) between the modSLA and anodized surfaces. RESULTS: The roughness of the anodized surface was 1.22 +/- 0.17 um in Sa, which was within the optimal range of 1.0-2.0 um for a bone response. The modSLA surface was significantly rougher at 2.53 +/- 0.07 um in Sa. However, the modSLA implant had significantly higher BIC than the anodized implant (P=0.02). Furthermore, BA ratios did not significantly differ between the two implants, although the anodized implant had a higher mean value of BA (P>0.05). CONCLUSIONS: Within the limitations of this study, the hydrophilicity of the modSLA surface may have a stronger effect on in vivo bone healing than optimal surface roughness and surface chemistry of the anodized surface. PMID- 26131370 TI - Hyperglycemia increases the expression levels of sclerostin in a reactive oxygen species- and tumor necrosis factor-alpha-dependent manner. AB - PURPOSE: Sclerostin, an inhibitor of Wnt/beta-catenin signaling, exerts negative effects on bone formation and contributes to periodontitis-induced alveolar bone loss. Recent studies have demonstrated that serum sclerostin levels are increased in diabetic patients and that sclerostin expression in alveolar bone is enhanced in a diabetic periodontitis model. However, the molecular mechanism of how sclerostin expression is enhanced in diabetic patients remains elusive. Therefore, in this study, the effect of hyperglycemia on the expression of sclerostin in osteoblast lineage cells was examined. METHODS: C2C12 and MLO-Y4 cells were used in this study. In order to examine the effect of hyperglycemia, the glucose concentration in the culture medium was adjusted to a range of levels between 40 and 100 mM. Gene expression levels were examined by quantitative reverse transcription-polymerase chain reaction and Western blot assays. Top Flash reporter was used to examine the transcriptional activity of the beta catenin/lymphoid enhanced factor/T-cell factor complex. Tumor necrosis factor alpha (TNFalpha) protein levels were examined with the enzyme-linked immunosorbent assay. The effect of reactive oxygen species on sclerostin expression was examined by treating cells with 1 mM H2O2 or 20 mM N acetylcysteine. RESULTS: The high glucose treatment increased the mRNA and protein levels of sclerostin. High glucose suppressed Wnt3a-induced Top-Flash reporter activity and the expression levels of osteoblast marker genes. High glucose increased reactive oxygen species production and TNFalpha expression levels. Treatment of cells with H2O2 also enhanced the expression levels of TNFalpha and sclerostin. In addition, N-acetylcysteine treatment or knockdown of TNFalpha attenuated high glucose-induced sclerostin expression. CONCLUSIONS: These results suggest that hyperglycemia increases sclerostin expression via the enhanced production of reactive oxygen species and TNFalpha. PMID- 26131371 TI - Effect of fibroblast growth factor on injured periodontal ligament and cementum after tooth replantation in dogs. AB - PURPOSE: The purpose of this animal study was to perform a histological and histomorphometric analysis in order to elucidate the effect of fibroblast growth factor-2 (FGF-2) on injured periodontal ligament (PDL) and cementum after tooth replantation in dogs. METHODS: The roots of 36 mandibular premolars from six mongrel dogs were used in this study. The roots were randomly divided into three groups: (1) a positive control group (n=12), in which the PDL was retained; (2) a negative control group (n=12), in which the PDL and the cementum between the notches were removed; and (3) an experimental group (n=12), in which the PDL and the cementum between the notches were removed and the roots were soaked in an FGF 2 solution (30 ug/0.1 mL). After treating the root surfaces, the extracted roots were replanted into extraction sockets. The animals were sacrificed four and eight weeks after surgery for histologic and histomorphometric evaluation. RESULTS: At four and eight weeks, normal PDLs covered the roots in the positive control group. In the negative control group, most replanted roots showed signs of replacement resorption. In the experimental group, new PDL-like tissue and cementum-like tissue were observed to partially occupy the region between the root surfaces and the newly formed bone. Histomorphometric analysis showed that the mean length of the newly formed cementum-like tissue on the roots treated with FGF-2 was significantly greater than that of the tissue on the roots in the negative control group (four weeks, P=0.008; eight weeks, P=0.042). However, no significant differences were observed between the roots treated with FGF-2 and the negative control roots with respect to newly formed PDL-like tissue. CONCLUSIONS: The results of this study suggest that use of FGF-2 on injured root surfaces promotes cementogenesis after tooth replacement in dogs. PMID- 26131372 TI - Microgrooves on titanium surface affect peri-implant cell adhesion and soft tissue sealing; an in vitro and in vivo study. AB - PURPOSE: With the significance of stable adhesion of alveolar bone and peri implant soft tissue on the surface of titanium for successful dental implantation procedure, the purpose of this study was to apply microgrooves on the titanium surface and investigate their effects on peri-implant cells and tissues. METHODS: Three types of commercially pure titanium discs were prepared; machined-surface discs (A), sandblasted, large-grit, acid-etched (SLA)-treated discs (B), SLA and microgroove-formed discs (C). After surface topography of the discs was examined by confocal laser scanning electron microscopy, water contact angle and surface energy were measured. Human gingival fibroblasts (hGFs) and murine osteoblastic cells (MC3T3-E1) were seeded onto the titanium discs for immunofluorescence assay of adhesion proteins. Commercially pure titanium implants with microgrooves on the coronal microthreads design were inserted into the edentulous mandible of beagle dogs. After 2 weeks and 6 weeks of implant insertion, the animal subjects were euthanized to confirm peri-implant tissue healing pattern in histologic specimens. RESULTS: Group C presented the lowest water contact angle (62.89+/ 5.66 theta), highest surface energy (45+/-1.2 mN/m), and highest surface roughness (Ra=22.351+/-2.766 um). The expression of adhesion molecules of hGFs and MC3T30E1 cells was prominent in group C. Titanium implants with microgrooves on the coronal portion showed firm adhesion to peri-implant soft tissue. CONCLUSIONS: Microgrooves on the titanium surface promoted the adhesion of gingival fibroblasts and osteoblastic cells, as well as favorable peri-implant soft tissue sealing. PMID- 26131373 TI - Beliefs in being unlucky and deficits in executive functioning: an ERP study. AB - There has been initial evidence to support the Dysexecutive Luck hypothesis, which proposes that beliefs in being unlucky are associated with deficits in executive functioning (Maltby et al., 2013). The present study tested the Dysexecutive Luck hypothesis by examining whether deficits in the early stage of top down attentional control led to an increase of neural activity in later stages of response related selection process among those who thought themselves to be unlucky. Individuals with these beliefs were compared to a control group using an Event-Related Potential (ERP) measure assessing underlying neural activity of semantic inhibition while completing a Stroop test. Results showed stronger main interference effects in the former group, via greater reaction times and a more negative distributed scalp late ERP component during incongruent trials in the time window of 450-780 ms post stimulus onset. Further, less efficient maintenance of task set among the former group was associated with greater late ERP response-related activation to compensate for the lack of top down attentional control. These findings provide electrophysiological evidence to support the Dysexecutive Luck hypothesis. PMID- 26131374 TI - FDAAA legislation is working, but methodological flaws undermine the reliability of clinical trials: a cross-sectional study. AB - The relationship between clinical research and the pharmaceutical industry has placed clinical trials in jeopardy. According to the medical literature, more than 70% of clinical trials are industry-funded. Many of these trials remain unpublished or have methodological flaws that distort their results. In 2007, it was signed into law the Food and Drug Administration Amendments Act (FDAAA), aiming to provide publicly access to a broad range of biomedical information to be made available on the platform ClinicalTrials (available at https://www.clinicaltrials.gov). We accessed ClinicalTrials.gov and evaluated the compliance of researchers and sponsors with the FDAAA. Our sample comprised 243 protocols of clinical trials of biological monoclonal antibodies (mAb) adalimumab, bevacizumab, infliximab, rituximab, and trastuzumab. We demonstrate that the new legislation has positively affected transparency patterns in clinical research, through a significant increase in publication and online reporting rates after the enactment of the law. Poorly designed trials, however, remain a challenge to be overcome, due to a high prevalence of methodological flaws. These flaws affect the quality of clinical information available, breaching ethical duties of sponsors and researchers, as well as the human right to health. PMID- 26131375 TI - Responses to simulated nitrogen deposition by the neotropical epiphytic orchid Laelia speciosa. AB - Potential ecophysiological responses to nitrogen deposition, which is considered to be one of the leading causes for global biodiversity loss, were studied for the endangered endemic Mexican epiphytic orchid, Laelia speciosa, via a shadehouse dose-response experiment (doses were 2.5, 5, 10, 20, 40, and 80 kg N ha(-1) yr(-1)) in order to assess the potential risk facing this orchid given impending scenarios of nitrogen deposition. Lower doses of nitrogen of up to 20 kg N ha yr(-1), the dose that led to optimal plant performance, acted as fertilizer. For instance, the production of leaves and pseudobulbs were respectively 35% and 36% greater for plants receiving 20 kg N ha yr(-1) than under any other dose. Also, the chlorophyll content and quantum yield peaked at 0.66 +/- 0.03 g m(-2) and 0.85 +/- 0.01, respectively, for plants growing under the optimum dose. In contrast, toxic effects were observed at the higher doses of 40 and 80 kg N ha yr(-1). The delta (13)C for leaves averaged -14.7 +/- 0.20/00 regardless of the nitrogen dose. In turn, delta (15)N decreased as the nitrogen dose increased from 0.9 +/- 0.10/00 under 2.5 kg N ha(-1)yr(-1) to -3.1 +/- 0.20/00 under 80 kg N ha(-1)yr(-1), indicating that orchids preferentially assimilate NH4 (+) rather than NO3 (-) of the solution under higher doses of nitrogen. Laelia speciosa showed a clear response to inputs of nitrogen, thus, increasing rates of atmospheric nitrogen deposition can pose an important threat for this species. PMID- 26131376 TI - Primate tarsal bones from Egerkingen, Switzerland, attributable to the middle Eocene adapiform Caenopithecus lemuroides. AB - The middle Eocene species Caenopithecus lemuroides, known solely from the Egerkingen fissure fillings in Switzerland, was the first Paleogene fossil primate to be correctly identified as such (by Ludwig Rutimeyer in 1862), but has long been represented only by fragmentary mandibular and maxillary remains. More recent discoveries of adapiform fossils in other parts of the world have revealed Caenopithecus to be a biogeographic enigma, as it is potentially more closely related to Eocene adapiforms from Africa, Asia, and North America than it is to any known European forms. More anatomical evidence is needed, however, to provide robust tests of such phylogenetic hypotheses. Here we describe and analyze the first postcranial remains that can be attributed to C. lemuroides-an astragalus and three calcanei held in the collections of the Naturhistorisches Museum Basel that were likely recovered from Egerkingen over a century ago. Qualitative and multivariate morphometric analyses of these elements suggest that C. lemuroides was even more loris-like than European adapines such as Adapis and Leptadapis, and was not simply an adapine with an aberrant dentition. The astragalus of Caenopithecus is similar to that of younger Afradapis from the late Eocene of Egypt, and parsimony and Bayesian phylogenetic analyses that include the new tarsal data strongly support the placement of Afradapis and Caenopithecus as sister taxa to the exclusion of all other known adapiforms, thus implying that dispersal between Europe and Africa occurred during the middle Eocene. The new tarsal evidence, combined with previously known craniodental fossils, allows us to reconstruct C. lemuroides as having been an arboreal and highly folivorous 1.5 2.5 kg primate that likely moved slowly and deliberately with little or no capacity for acrobatic leaping, presumably maintaining consistent powerful grasps on branches in both above-branch and inverted postures. PMID- 26131377 TI - The invasive land planarian Platydemus manokwari (Platyhelminthes, Geoplanidae): records from six new localities, including the first in the USA. AB - The land planarian Platydemus manokwari de Beauchamp, 1963 or "New Guinea flatworm" is a highly invasive species, mainly in the Pacific area, and recently in Europe (France). We report specimens from six additional countries and territories: New Caledonia (including mainland and two of the Loyalty Islands, Lifou and Mare), Wallis and Futuna Islands, Singapore, Solomon Islands, Puerto Rico, and Florida, USA. We analysed the COI gene (barcoding) in these specimens with two sets of primers and obtained 909 bp long sequences. In addition, specimens collected in Townsville (Australia) were also sequenced. Two haplotypes of the COI sequence, differing by 3.7%, were detected: the "World haplotype" found in France, New Caledonia, French Polynesia, Singapore, Florida and Puerto Rico; and the "Australian haplotype" found in Australia. The only locality with both haplotypes was in the Solomon Islands. The country of origin of Platydemus manokwari is New Guinea, and Australia and the Solomon Islands are the countries closest to New Guinea from which we had specimens. These results suggest that two haplotypes exist in the area of origin of the species, but that only one of the two haplotypes (the "World haplotype") has, through human agency, been widely dispersed. However, since P. manokwari is now recorded from 22 countries in the world and we have genetic information from only 8 of these, with none from New Guinea, this analysis provides only partial knowledge of the genetic structure of the invasive species. Morphological analysis of specimens from both haplotypes has shown some differences in ratio of the genital structures but did not allow us to interpret the haplotypes as different species. The new reports from Florida and Puerto Rico are firsts for the USA, for the American continent, and the Caribbean. P. manokwari is a known threat for endemic terrestrial molluscs and its presence is a matter of concern. While most of the infected territories reported until now were islands, the newly reported presence of the species in mainland US in Florida should be considered a potential major threat to the whole US and even the Americas. PMID- 26131378 TI - Sensitivity to the visual field origin of natural image patches in human low level visual cortex. AB - Asymmetries in the response to visual patterns in the upper and lower visual fields (above and below the centre of gaze) have been associated with ecological factors relating to the structure of typical visual environments. Here, we investigated whether the content of the upper and lower visual field representations in low-level regions of human visual cortex are specialised for visual patterns that arise from the upper and lower visual fields in natural images. We presented image patches, drawn from above or below the centre of gaze of an observer navigating a natural environment, to either the upper or lower visual fields of human participants (n = 7) while we used functional magnetic resonance imaging (fMRI) to measure the magnitude of evoked activity in the visual areas V1, V2, and V3. We found a significant interaction between the presentation location (upper or lower visual field) and the image patch source location (above or below fixation); the responses to lower visual field presentation were significantly greater for image patches sourced from below than above fixation, while the responses in the upper visual field were not significantly different for image patches sourced from above and below fixation. This finding demonstrates an association between the representation of the lower visual field in human visual cortex and the structure of the visual input that is likely to be encountered below the centre of gaze. PMID- 26131379 TI - A Bayesian approach to optimizing cryopreservation protocols. AB - Cryopreservation is beset with the challenge of protocol alignment across a wide range of cell types and process variables. By taking a cross-sectional assessment of previously published cryopreservation data (sample means and standard errors) as preliminary meta-data, a decision tree learning analysis (DTLA) was performed to develop an understanding of target survival using optimized pruning methods based on different approaches. Briefly, a clear direction on the decision process for selection of methods was developed with key choices being the cooling rate, plunge temperature on the one hand and biomaterial choice, use of composites (sugars and proteins as additional constituents), loading procedure and cell location in 3D scaffolding on the other. Secondly, using machine learning and generalized approaches via the Naive Bayes Classification (NBC) method, these metadata were used to develop posterior probabilities for combinatorial approaches that were implicitly recorded in the metadata. These latter results showed that newer protocol choices developed using probability elicitation techniques can unearth improved protocols consistent with multiple unidimensionally-optimized physical protocols. In conclusion, this article proposes the use of DTLA models and subsequently NBC for the improvement of modern cryopreservation techniques through an integrative approach. PMID- 26131380 TI - Life as a bachelor: quantifying the success of an alternative reproductive tactic in male blue monkeys. AB - In species that live in one-male groups, resident males monopolize access to a group of females and are assumed to have higher reproductive success than bachelors. We tested this assumption using genetic, demographic, and behavioral data from 8 groups of wild blue monkeys observed over 10 years to quantify reproduction by residents and bachelors and compare the success of the two tactics. We used maximum-likelihood methods to assign sires to 104 offspring born in the study groups, 36 of which were sired by extra-group males, i.e., residents of neighboring groups and bachelors. Among these extra-group males, high-ranking males (many of whom were neighboring residents) were more likely to sire offspring than low-ranking males, but the time these visiting males spent in the mother's group when she conceived (male presence) did not predict their relative success. When bachelors competed for reproduction with other bachelors, neither rank nor male presence during the mother's conceptive period affected the probability of siring an offspring, suggesting that highly opportunistic mating with conceptive females is important in bachelor reproduction. In a second analysis, we used long-term data to estimate resident and bachelor reproductive success over the long term, and particularly to determine if there are any circumstances in which a typical bachelor may sire as many offspring as a typical resident during one or two periods of residency. Our findings generally support the assumption of a resident reproductive advantage because in most circumstances, a lifelong bachelor would be unable to sire as many offspring as a resident. However, a bachelor who performs at the average rate in the average number of groups for several years may have similar lifetime reproductive success as a male whose reproduction is limited to one short period of residency, especially in a small group. Our findings suggest that one should not assume a resident reproductive advantage for males in one-male groups in all circumstances. PMID- 26131381 TI - Nothing Hurts Follow-Up like Follow-Up? PMID- 26131382 TI - Success in Spine Care: The Proof Is in the Measurements, Part I. PMID- 26131383 TI - Expandable Polyaryl-Ether-Ether-Ketone Spacers for Interbody Distraction in the Lumbar Spine. AB - Study Design Retrospective case series. Objective StaXx XD (Spine Wave, Inc., Shelton, CT, United States) is an expandable polyaryl-ether-ether-ketone (PEEK) wafer implant utilized in the treatment of lumbar degenerative disease. PEEK implants have been successfully used as interbody devices. Few studies have focused on expandable PEEK devices. The aim of the current study is to determine the radiographic and clinical outcome of expandable PEEK cages utilized for transforaminal lumbar interbody fusion in patients with lumbar degenerative diseases. Methods Forty-nine patients who underwent lumbar interbody fusion with implantation of expandable PEEK cages and posterior instrumentation were included. The clinical outcome was evaluated using the visual analog scale (VAS) and the Oswestry Disability Index (ODI). Radiographic parameters including disk height, foraminal height, listhesis, local disk angle of the index level/levels, regional lumbar lordosis, and graft subsidence were measured preoperatively, postoperatively, and at latest follow-up. Results At an average follow-up of 19.3 months, the minimum clinically important difference for the ODI and VAS back, buttock, and leg were achieved in 64, 52, 58, and 52% of the patients, respectively. There was statistically significant improvement in VAS back (6.42 versus 3.11, p < 0.001), VAS buttock (4.66 versus 1.97, p = 0.002), VAS leg (4.55 versus 1.96, p < 0.001), and ODI (21.7 versus 12.1, p < 0.001) scores. There was a significant increase in the average disk height (6.49 versus 8.18 mm, p = 0.037) and foraminal height (15.6 versus 18.53 mm, p = 0.0001), and a significant reduction in the listhesis (5.13 versus 3.15 mm, p = 0.005). The subsidence of 0.66 mm (7.4%) observed at the latest follow-up was not significant (p = 0.35). Conclusions Midterm results indicate that expandable PEEK spacers can effectively and durably restore disk and foraminal height and improve the outcome without significant subsidence. PMID- 26131384 TI - Adolescent Idiopathic Scoliosis and Pregnancy: An Unsolved Paradigm. AB - Study Design Retrospective cohort study with a cross-sectional comparison. Objective To compare the rates of anesthesia prescription and satisfaction with surgery, prevalence and severity of low back pain, prevalence of depression, and sexual dysfunction among pregnant and nonpregnant patients with AIS undergoing correction surgery with pedicle-based systems and healthy woman with a history of pregnancy. Methods Women between the ages of 18 and 40 years who underwent correction surgery for AIS with a pedicle screw system were interviewed regarding pregnancies, child delivery, method of pain control during delivery, and any long term outcome after delivery. In addition, sexual dysfunction (Female Sexual Distress Scale-Revised [FSDS]), depression (the Beck Depression Assessment Questionnaire), and Scoliosis Research Society 24 (SRS24) questionnaires were administered. Data was compared between patients with AIS without a history of pregnancy and healthy controls. Results Satisfaction with surgery in the AIS pregnant group using the SRS24 questionnaire scored 3.76/5 (p = 0.0047 when compared with nonpregnant AIS group). Six of the 17 of the women with AIS had severe back pain during pregnancy (35%) mandating home treatment or hospitalization. Of the 17 women, 13 complained of a sustained back pain after child delivery (76%) that impacted their life. In the nonscoliosis group, no back pain attributed to pregnancy was reported. The rates of regional anesthesia prescription among pregnant patients with AIS who underwent correction surgery was 30% (5/17), whereas among healthy pregnant women, rates were 100% (6/6). The SRS24 scores in the patients with AIS were 72% (88/120), showing a low score of 3.69/5 in the pain domains (p = 0.0048 when compared with nonpregnant patients with AIS). Depression rates were in the normal range and similar in all groups. FSDS scores, used to assess sexual dysfunction, were 4.02 in the pregnancy group and 5.67 in the nonpregnant group (not significant) and 4.6 in the nonscoliosis control group (not significant). Conclusion Women who underwent scoliosis correction suffered from long-term back pain after pregnancy and had decreased satisfaction with surgery. In addition, anesthesiologists refused epidurals in a large number of these patients. A larger study is needed on the topic. PMID- 26131385 TI - Unilateral versus Bilateral Instrumentation in Spinal Surgery: A Systematic Review. AB - Study Design Systematic review. Clinical Questions (1) What is the comparative efficacy of unilateral instrumentation compared with bilateral instrumentation in spine surgery? (2) What is the safety of unilateral instrumentation compared with bilateral instrumentation in spine surgery? Methods Electronic databases and reference lists of key articles were searched up to September 30, 2014, to identify studies reporting the comparative efficacy and safety of unilateral versus bilateral instrumentation in spine surgery. Studies including recombinant human bone morphogenetic protein 2 as adjunct therapy and those with follow-up of less than 2 years were excluded. Results Ten randomized controlled trials met the inclusion criteria: five compared unilateral with bilateral instrumentation using open transforaminal or posterior lumbar interbody fusion (TLIF/PLIF), one used open posterolateral fusion, and four used minimally invasive TLIF/PLIF. There were no significant differences between unilateral and bilateral screw instrumentation with respect to nonunion, low back or leg pain scores, Oswestry Disability Index, reoperation, or complications. Conclusions The existing literature does not identify significant differences in clinical outcomes, union rates, and complications when unilateral instrumentation is used for degenerative pathologic conditions in the lumbar spine. The majority of published reports involve single-level lumbar unilateral instrumentation. PMID- 26131386 TI - Iliac Crest Bone Graft in Lumbar Fusion: The Effectiveness and Safety Compared with Local Bone Graft, and Graft Site Morbidity Comparing a Single-Incision Midline Approach with a Two-Incision Traditional Approach. AB - Study Design Systematic review. Clinical Questions (1) Is autologous local bone (LB) graft as safe and effective as iliac crest bone graft (ICBG) in lumbar spine fusion? (2) In lumbar fusion using ICBG, does a single-incision midline approach reduce postoperative iliac crest pain compared with a two-incision traditional approach? Methods Electronic databases and reference lists of key articles were searched up to October 2014 to identify studies reporting the comparative efficacy and safety of ICBG versus LB graft or comparing ICBG harvest site for use in lumbar spine surgery. Studies including allograft, synthetic bone, or growth factors in addition to ICBG and those with less than 80% of patients with degenerative disease in the lumbar spine were excluded. Two independent reviewers assessed the level of the evidence quality using the Grades of Recommendation Assessment, Development and Evaluation criteria, and disagreements were resolved by consensus. Results Seven studies were identified as using ICBG fusion for degenerative disease in the lumbar spine. There were no differences in the fusion, leg pain, low back pain, or functional outcomes between patients receiving LB versus ICBG. There was a higher incidence of donor site pain and sensory loss in patients receiving ICBG, with no donor site complications attributed to LB. Compared with patients with the graft harvested through the two incision traditional approach, patients with the graft harvested through the single-incision midline approach had lower mean pain scores over the iliac crest, with a higher proportion reporting no iliac crest tenderness. In patients with ICBG harvested through the single-incision midline approach on either the right or the left side of the ilium, only 36% of the patients were able to correctly identify the side when asked whether they knew which iliac crest was harvested. Only 19% of the patients with ICBG harvested through the single-incision midline approach on either the right or the left side of the ilium reported pain that was concordant with the side that was actually harvested. Conclusions LB is as safe and efficacious as ICBG for instrumented fusion in the lumbar spine to treat degenerative disease. When ICBG is used, graft harvest through the single incision midline approach reduces postoperative iliac crest pain compared with a two-incision approach. PMID- 26131387 TI - Quality and Quantity of Published Studies Evaluating Lumbar Fusion during the Past 10 Years: A Systematic Review. AB - Study Design Systematic review. Clinical Questions (1) Has the proportion and number of randomized controlled trials (RCTs) as an indicator of quality of evidence regarding lumbar fusion increased over the past 10 years? (2) Is there a difference in the proportion of RCTs among the four primary fusion diagnoses (degenerative disk disease, spondylolisthesis, deformity, and adjacent segment disease) over the past 10 years? (3) Is there a difference in the type and quality of clinical outcomes measures reported among RCTs over time? (4) Is there a difference in the type and quality of adverse events measures reported among RCTs over time? (5) Are there changes in fusion surgical approach and techniques over time by diagnosis over the past 10 years? Methods Electronic databases and reference lists of key articles were searched from January 1, 2004, through December 31, 2013, to identify lumbar fusion RCTs. Fusion studies designed specifically to evaluate recombinant human bone morphogenetic protein-2 or other bone substitutes, revision surgery studies, nonrandomized comparison studies, case reports, case series, and cost-effectiveness studies were excluded. Results Forty-two RCTs between January 1, 2004, and December 31, 2013, met the inclusion criteria and form the basis for this report. There were 35 RCTs identified evaluating patients diagnosed with degenerative disk disease, 4 RCTs evaluating patients diagnosed with degenerative spondylolisthesis, and 3 RCTs evaluating patients with a combination of degenerative disk disease and degenerative spondylolisthesis. No RCTs were identified evaluating patients with deformity or adjacent segment disease. Conclusions This structured review demonstrates that there has been an increase in the available clinical database of RCTs using patient-reported outcomes evaluating the benefit of lumbar spinal fusion for the diagnoses of degenerative disk disease and degenerative spondylolisthesis. Gaps remain in the standardization of reportage of adverse events in such trials, as well as uniformity of surgical approaches used. Finally, continued efforts to develop higher-quality data for other surgical indications for lumbar fusion, most notably in the presence of adult spinal deformity and revision of prior surgical fusions, appear warranted. PMID- 26131388 TI - Postoperative Shingles Mimicking Recurrent Radiculopathy after Anterior Cervical Diskectomy and Fusion. AB - Study Design Case report and review of literature. Objective To report the case of a 67-year-old woman who developed delayed onset (6 months) of symptomatic shingles after cervical nerve root decompression in a previously symptomatic dermatome. Methods The patient's clinic course and outcomes were retrospectively reviewed. The study required no outside funding. The study authors have no financial interest in any of the products or techniques discussed. Results The patient received definitive treatment for shingles once the zoster form rash manifested. The patient, however, developed postherpetic neuralgia and remained symptomatic at her 2-year postoperative visit. Conclusions Although shingles is a common disease state affecting patients in the fifth and sixth decades of life, it is rarely seen in the setting of cervical nerve root decompression. This case demonstrates the need to include shingles on the differential diagnosis of recurrent neurogenic pain after anterior cervical decompression and fusion. PMID- 26131389 TI - Commentary on: "Postoperative Shingles Mimicking Recurrent Radiculopathy after Anterior Cervical Diskectomy and Fusion". PMID- 26131390 TI - Traumatic Spondylopelvic Dissociation: A Report of Two Cases of Spondylolisthesis at L5-S1 and Review of Literature. AB - Study Design Retrospective chart review and review of literature. Objective Few case reports of traumatic L5-S1 displacement have been presented in the literature. Here we present two cases of traumatic spondylolisthesis showing both anterior and posterior displacement, the treatment algorithm, and a review of the literature. Methods The authors conducted a retrospective review of representative patients and a literature review of traumatic spondylolisthesis at the L5-S1 junction. Two representative patients were identified with traumatic spondylolisthesis: one with an anterior dissociation, and the other with a posterior dissociation. Results Radiographic, computed tomography, and magnetic resonance imaging illustrated the bony and soft tissue injury found in each patient, as well as the final stabilization and outcomes. Operative stabilization was necessary, and both patients were treated with open reduction internal fixation. The patient with posterior dissociation had complete recovery without neurologic sequelae. The patient with anterior dissociation had persistent bilateral L5-S1 radiculopathy with intact rectal tone, due to neurologic compression. Conclusions Few cases of traumatic spondylopelvic dissociation that are isolated to the L5-S1 disk space are described in the literature. We examined both an anterior and a posterior dissociation and treated both with L5-S1 posterior spinal fusion. The patient with anterior dissociation had persistent L5 S1 root injury; however, the patient with posterior dissociation had no neurologic deficits. This is the opposite of what is expected based on anatomy. These cases offer insight into the management of anterior and posterior L5-S1 spondylopelvic dissociation. PMID- 26131391 TI - Commentary on: "Traumatic Spondylopelvic Dissociation: A Report of Two Cases of Spondylolisthesis at L5-S1 and Review of Literature". PMID- 26131392 TI - Spontaneous Ankylosis of Occiput to C2 following Closed Traction and Halo Treatment of Atlantoaxial Rotary Fixation. AB - Study Design Case report. Objective We report a case of spontaneous atlantoaxial rotatory fixation (AARF) presenting 9 months after onset in an 11-year-old boy. Methods This is a retrospective case report of spontaneous ankylosis of occiput to C2 following traction, manipulative reduction, and halo immobilization for refractory atlantoaxial rotatory fixation. Results The patient underwent traction followed by close manual reduction and placement of halo immobilization after 6 months of severe spontaneous-onset AARF that had been refractory to chiropractic manipulation and physical therapy. Imaging demonstrated dislocation of the left C1-C2 facet joint and remodeling changes of the C2 superior facet prior to reduction, followed by near complete reduction of the dislocation after manipulation and halo placement. Symptoms and clinical appearance were satisfactorily improved and the halo vest was removed after 3 months. At late follow-up, computed tomography demonstrated complete bony ankylosis of the occiput to C2. The patient was found to be HLA B27-positive, but he had no family history of ankylosing spondyloarthropathy or other joint symptoms. The underlying reasons for spontaneous fusion of the occiput to C2 could include the traction, HLA-B27-related spondyloarthropathy, or arthropathic changes caused by traction, reduction, the inciting insult, or immobilization. Conclusion When discussing treatment of childhood refractory AARF by traction, closed manipulation, and halo immobilization, the possibility of developing "spontaneous" ankylosis needs to be considered. PMID- 26131393 TI - Commentary on: "Spontaneous Ankylosis of Occiput to C2 following Closed Traction and Halo Treatment of Atlantoaxial Rotary Fixation". PMID- 26131394 TI - Spinal Myeloid Sarcoma "Chloroma" Presenting as Cervical Radiculopathy: Case Report. AB - Study Design Case report. Objective Myeloid sarcoma (also known as chloroma) is a rare, extramedullary tumor composed of immature granulocytic cells. It may occur early in the course of acute or chronic leukemia or myeloproliferative disorders. Spinal cord invasion by myeloid sarcoma is rare. The authors report a rare case of spinal myeloid sarcoma presenting as cervical radiculopathy. Methods A previously healthy 43-year-old man presented with progressive neck, right shoulder, and arm pain. Cervical magnetic resonance imaging (MRI) revealed a very large enhancing extradural soft tissue mass extending from C7 through T1, with severe narrowing of the thecal sac at the T1 level. The patient underwent posterior cervical open biopsy, laminectomy, and decompression. Histologic examination of the surgical specimen confirmed the diagnosis of myeloid sarcoma. Postoperatively, a bone marrow biopsy was done, which showed myeloproliferative neoplasm with eosinophilia. The patient then received systemic chemotherapy and radiotherapy. Results At the 10-month follow-up, the patient reported complete relief of arm pain and neck pain. X-rays showed that the overall cervical alignment was intact and there was no evidence of a recurrent lesion. MRI showed no evidence of compressive or remnant lesion. Conclusions Spinal myeloid sarcoma presenting as cervical radiculopathy is rare, and it may be easily misdiagnosed. Knowledge of its clinical presentation, imaging, and histologic characterization can lead to early diagnosis and appropriate treatment. PMID- 26131395 TI - Commentary on: "Spinal Myeloid Sarcoma 'Chloroma' Presenting as Cervical Radiculopathy: Case Report". PMID- 26131396 TI - Atraumatic Sacral Fracture in Late Pregnancy: A Case Report. AB - Study Design Case report. Objective Sacral fractures, traumatic or atraumatic, are a rather rare cause of low back pain. The majority of the cases of pregnancy related sacral fractures are reported as a postpartum complication, and only few cases of sacral atraumatic fractures have been reported in the last trimester of the pregnancy. The aim of this study is to report a rare case of atraumatic sacral fracture in the third trimester of pregnancy. Methods We report the case of a 30-year-old Caucasian European woman during her 37th week (36 weeks and 4 days) of gestation, who complained during her scheduled obstetric examination of continuous low back pain with no associated history of trauma. The patient performed activities of daily living with a normal level of fatigue and reported no running or walking long distances. She was examined in our department, and a magnetic resonance imaging scan was performed that showed a vertical nondisplaced fracture in her left sacrum. Results The patient was treated conservatively, and analgesics were administrated according to the consensus of the orthopedic and the anesthesiology departments. No further complications were recognized in the remaining period of her pregnancy, and a healthy child was born by caesarean section. Conclusions Atraumatic fractures of the sacrum should be included in the differentiated diagnosis of pregnant patients with low back pain. PMID- 26131397 TI - Commentary on: "Atraumatic Sacral Fracture in Late Pregnancy: A Case Report". PMID- 26131398 TI - Fatal Isolated Cervical Spine Injury in a Patient with Ankylosing Spondylitis: A Case Report. AB - Study Design Case report. Objective The purpose of the present case report was to present a patient with a history of ankylosing spondylitis who sustained a dislocation of C6 on C7 and died soon after his presentation in the emergency room (ER). Methods An 88-year-old man was brought to the ER due to a neck injury secondary to a fall. Imaging of the cervical spine revealed anterior dislocation of C6 on C7 and the characteristic "bamboo" spine of ankylosing spondylitis. Results The patient died within 30 minutes due to respiratory insufficiency. Conclusion Isolated cervical spine injuries in patients with ankylosing spondylitis can be fatal. A high degree of clinical suspicion, thorough imaging with computed tomography, and meticulous handling are required in this patient population. PMID- 26131399 TI - Commentary on: "Fatal Isolated Cervical Spine Injury in a Patient with Ankylosing Spondylitis: A Case Report". PMID- 26131400 TI - Letter to the Editor on: "Sterile Seroma Resulting from Multilevel XLIF Procedure as Possible Adverse Effect of Prophylactic Vancomycin Powder: A Case Report" (Evid Based Spine Care J 2014;5(2):127-133). PMID- 26131402 TI - Definition of levels of evidence (LoE) and overall strength of evidence (SoE). PMID- 26131401 TI - Reply to the Letter to the Editor on: "Sterile Seroma Resulting from Multilevel XLIF Procedure as Possible Adverse Effect of Prophylactic Vancomycin Powder: A Case Report" (Evid Based Spine Care J 2014;5(2):127-133). PMID- 26131403 TI - Stability and Load Sharing Characteristics of a Posterior Dynamic Stabilization Device. AB - BACKGROUND: Lumbar interbody fusion is a common treatment for a variety of spinal pathologies. It has been hypothesized that insufficient mechanical loading of the interbody graft can prevent proper fusion of the joint. The purpose of this study was to evaluate the mechanical stability and anterior column loading sharing characteristics of a posterior dynamic system compared to titanium rods in an anterior lumbar interbody fusion (ALIF) model. METHODS: Range of motion, interpedicular kinematics and interbody graft loading were measured in human cadaveric lumbar segments tested under a pure moment flexibility testing protocol. RESULTS: Both systems provided significant fixation compared to the intact condition and to an interbody spacer alone in flexion extension and lateral bending. No significant differences in fixation were detected between the devices. A significant decrease in graft loading was detected in flexion for the titanium rod treatment compared to spacer alone. No significant differences in graft loading were detected between the spacer alone and posterior dynamic system or between the posterior dynamic system and the titanium rod. CONCLUSIONS: The results of this study indicate that the posterior dynamic system provides similar fixation compared to that of a titanium rod, however, studies designed to evaluate the efficacy of fixation in a cadaver model may not be sufficiently powered to establish differences in load sharing using the techniques described here. PMID- 26131404 TI - Clinical Outcomes After Cervical Transcorporeal Microdecompression and Vertebral Body Access Channel Repair. AB - BACKGROUND: Although anterior cervical decompression and fusion (ACDF) can be performed using minimally invasive techniques, the extensive removal of anatomical keystones during decompression requires a segmental fusion to restore biomechanical stability. Treatment with arthrodesis techniques may result in a prolonged recovery time, loss of motion, and the need for further treatment if a pseudarthosis or adjacent segment disease occur. Transcorporeal micro decompression (TCMD) is a newly developed motion sparing, minimally invasive anterior cervical spine decompression procedure that utilizes a small channel through the cervical vertebral body to decompress areas of central or foraminal stenosis while preserving the native disc. Cervical decompression with TCMD can be performed as a stand-alone or hybrid procedure with ACDF at the adjacent levels. This study retrospectively assesses patient based clinical outcome measures in patients treated with TCMD. METHODS: A retrospective, non-randomized, single-center chart review of single surgeon experience with patients undergoing TCMD both with and without adjacent level ACDF using both a trajectory control guide and access channel repair. Statistical analyses were performed on pre and post-operative data collected using visual analog scale (VAS) and neck disability index (NDI) outcome measures. RESULTS: Among 62 patients, there were no cases of neurovascular injury, CSF leak, transfusion, or migration of repair implement. Revision surgery was required in 6.4% (n=4) patients. A subanalysis of outcome metrics was performed for patients that underwent standalone TCMD (TCMD group, n=42) and TCMD with concurrent ACDF at one or more levels (TCMD+ACDF group, n=20). TCMD group NDI improved from 20.0 to 2.7 at 1 year (p=0.0001); Axial VAS improved from 5.5 to 0.6 (p=0.0001); and Radiating VAS improved from 7.0 to 0.7 (p=0.0001). TCMD+ACDF group NDI improved from 22.0 to 4.0 at 1 year (p=0.004); Axial VAS improved from 7.1 to 1.2 (p=0.01); and Radiating VAS trended towards significant improvement from 6.4 to 2.3 (p=0.09). Mean return to work was 10 days in the TCMD group and 57 days in the TCMD+ACDF group. CONCLUSIONS: Within the limits of a retrospective, single-surgeon study, patients did experience both functional improvement and pain relief as measured by NDI and VAS respectively from standalone TCMD or combined ACDF / TCMD procedures. Definitive statements on long-term efficacy, disc space preservation, and motion preservation await further study. PMID- 26131405 TI - Changing organ allocation policy for kidney transplantation in the United States. AB - The new kidney allocation scheme (KAS) in effect since December 4(th) 2014 was designed to overcome the shortcomings of previous system. A key feature of the new KAS is preferential allocation of best quality organs to wait-list candidates with the longest predictive survival in a concept called longevity matching. Highly sensitized recipients would get extra points and enjoy widespread sharing of organs in order to increase accessibility to transplant. Wait-list candidates with blood group B will be offered organs from donors with A2 and A2B blood type in order to shorten their wait-list time. Time on the wait list will start from day of listing or date of initiation of dialysis whichever comes first which should benefit candidates with limited resources who might be late to get on the transplant list. Pay back system has been eliminated in the new KAS. These changes in organ allocation policy may lead to increase in median half-life of the allograft and increase the number of transplants; thus resulting in better utilization of a scarce resource. There could be unintended negative consequences which may become evident over time. PMID- 26131406 TI - Philosophy of organ donation: Review of ethical facets. AB - Transplantation ethics is a philosophy that incorporates systematizing, defending and advocating concepts of right and wrong conduct related to organ donation. As the demand for organs increases, it is essential to ensure that new and innovative laws, policies and strategies of increasing organ supply are bioethical and are founded on the principles of altruism and utilitarianism. In the field of organ transplantation, role of altruism and medical ethics values are significant to the welfare of the society. This article reviews several fundamental ethical principles, prevailing organ donation consent laws, incentives and policies related to the field of transplantation. The Ethical and Policy Considerations in Organ Donation after Circulatory Determination of Death outline criteria for death and organ retrieval. Presumed consent laws prevalent mostly in European countries maintain that the default choice of an individual would be to donate organs unless opted otherwise. Explicit consent laws require organ donation to be proactively affirmed with state registries. The Declaration of Istanbul outlines principles against organ trafficking and transplant tourism. World Health Organization's Guiding Principles on Human Cell, Tissue and Organ Transplantation aim at ensuring transparency in organ procurement and allocation. The ethics of financial incentives and non-financial incentives such as incorporation of non-medical criteria in organ priority allocation have also been reviewed in detail. PMID- 26131408 TI - Successful endovascular treatment of transplant intrarenal artery stenosis in renal transplant recipients: Two case reports. AB - Transplant renal artery stenosis (TRAS) is a relatively rare complication after renal transplantation. The site of the surgical anastomosis is most commonly involved, but sites both proximal and distal to the anastomosis may occur, as well. Angioplasty is the gold standard for the treatment of the stenosis, especially for intrarenal lesions. We report two cases of intrarenal TRAS and successful management with angioplasty without stent placement. Both patients were male, 44 and 55 years old respectively, and they presented with elevated blood pressure or serum creatinine within three months after transplantation. Subsequently, they have undergone angioplasty balloon dilatation with normalization of blood pressure and serum creatinine returning to baseline level. Percutaneous transluminal balloon renal angioplasty is a safe and effective method for the treatment of the intrarenal TRAS. PMID- 26131409 TI - A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M 1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application. AB - BACKGROUND: This study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode. METHODS: Sarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 uL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm*2.1 mm i.d., 2.6-um particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode. RESULTS: The developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R(2)>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance. CONCLUSIONS: A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects. PMID- 26131407 TI - Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment. AB - Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with delayed graft function, graft rejection, chronic rejection and chronic graft dysfunction. Ischemia/reperfusion affects many regulatory systems at the cellular level as well as in the renal tissue that result in a distinct inflammatory reaction of the kidney graft. Underlying factors of ischemia reperfusion include energy metabolism, cellular changes of the mitochondria and cellular membranes, initiation of different forms of cell death-like apoptosis and necrosis together with a recently discovered mixed form termed necroptosis. Chemokines and cytokines together with other factors promote the inflammatory response leading to activation of the innate immune system as well as the adaptive immune system. If the inflammatory reaction continues within the graft tissue, a progressive interstitial fibrosis develops that impacts long-term graft outcome. It is of particular importance in kidney transplantation to understand the underlying mechanisms and effects of ischemia/reperfusion on the graft as this knowledge also opens strategies to prevent or treat ischemia/reperfusion injury after transplantation in order to improve graft outcome. PMID- 26131410 TI - Accessory Gene Regulator Polymorphism and Vancomycin Minimum Inhibitory Concentration in Methicillin-Resistant Staphylococcus aureus. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with a vancomycin minimum inhibitory concentration (MIC) of 2 ug/mL presents a high rate of therapeutic failure in response to vancomycin. In addition, polymorphism in accessory gene regulator (agr) is associated with vancomycin therapeutic effects. The association between agr polymorphism and vancomycin MICs was investigated in MRSA isolates. METHODS: Agr group-specific PCR was conducted on 118 MRSA bloodstream isolates. Vancomycin susceptibility tests were conducted, while E test GRD (bioMerieux SA, France) was used to detect heterogeneous vancomycin intermediate S. aureus (hVISA). RESULTS: Of the 118 MRSA isolates, 59 (50.0%), 43 (36.4%), and 10 (8.5%) isolates belonged to agr group I, II, and III, respectively. Six isolates could not be classified. Twenty-six, 73, and 19 isolates presented a vancomycin MIC of 2, 1, and 0.5 ug/mL, respectively. Nine (34.6%), 14 (53.8%), and 2 (7.7%) isolates with MICs of 2 ug/mL belonged to agr group I, II, and III, respectively. Thirty-seven (50.6%), 26 (35.6%), and 6 (8.2%) isolates with MICs of 1 ug/mL belonged to agr group I, II, and III, respectively. Thirteen (68.4%), 3 (15.8%), and 2 (10.5%) isolates with MICs of 0.5 ug/mL belonged to agr group I, II, and III, respectively. The agr group II presented more isolates with MIC of 2 ug/mL (32.6%) than the agr non-group II (16%). Four isolates tested positive for hVISA. Three of them belonged to agr group II. CONCLUSIONS: MRSA isolates with vancomycin MIC of 2 ug/mL were more common in agr group II than in agr non-group II. PMID- 26131411 TI - Isolation and Identification of Clostridium difficile Using ChromID C. difficile Medium Combined With Gram Staining and PRO Disc Testing: A Proposal for a Simple Culture Process. AB - BACKGROUND: ChromID C. difficile agar (CDIF; bioMerieux, France), a chromogenic medium, allows for the isolation and identification of Clostridium difficile strains within 24 hr regardless of pretreatment of stool specimens with heat or alcohol shock. In the present study, we designed and evaluated a simple procedure for the implementation C. difficile cultures using CDIF medium in a tertiary hospital setting. METHODS: We designed a simple protocol for untreated stool specimens using CDIF medium followed by Gram staining and PRO disc (PRO disc K1532B, Key Scientific Products, USA) testing for the identification of C. difficile in colonies produced on CDIF agar. A total of 1,402 prospectively collected stool specimens from patients with suspected C. difficile infection were tested. The protocol was evaluated by phenotypic or molecular identification of C. difficile using Vitek 2 ANC card (bioMerieux) or 16S rDNA/tpi gene sequencing, respectively. RESULTS: Of 1,402 stool specimens, 650 isolates were cultured in CDIF. Overall, 235 (36.2%, 235/650) strains could be presumptively identified as C. difficile by using Gram staining and PRO disc testing. Of those, 231 (98.3%, 231/235) isolates were confirmed as true C. difficile by molecular assays. CONCLUSIONS: The use of CDIF combined with Gram staining and PRO disc testing of untreated stool specimens would allow for isolation and accurate identification of C. difficile strains and would be advantageous in reducing the multistep process for C. difficile culture. PMID- 26131412 TI - Characterization of Mucoid and Non-Mucoid Streptococcus pneumoniae Isolated From Outpatients. AB - BACKGROUND: Streptococcus pneumoniae causes pneumonia, sepsis, and meningitis. This study aimed to investigate the clinical characteristics of mucoid and non mucoid isolates of S. pneumoniae, and to explore the relationship between the isolate phenotypes and their antibiotic susceptibility. METHODS: Clinical isolates from 3,453 non-repetitive S. pneumoniae (189 mucoid and 3,264 non mucoid) infections obtained between January 2008 and December 2012 from outpatients at the Kimitsu-Central Hospital were evaluated. RESULTS: Compared to the non-mucoid isolates, the mucoid phenotypes were more susceptible to certain antibiotics such as erythromycin, clarithromycin, and tetracycline as opposed to clindamycin, chloramphenicol, and rifampicin. The mucoid phenotype was isolated more frequently from schoolchildren, adults, and elderly adults in a variety of clinical sites, including otorrhea, genitalia, pus, and eye discharge than the non-mucoid phenotype. This suggested that mucoid isolates are more likely to be involved than non-mucoid isolates in various local infections. Systemic infection, which indicates invasiveness, was not associated with the mucoid or non-mucoid phenotype. CONCLUSIONS: The results of this study suggest that mucoid isolates tend to have higher susceptibility than non-mucoid isolates to antibiotics. To the best of our knowledge, mucoid and non-mucoid S. pneumoniae isolates considerably differ in terms of clinical isolation site and age-specific prevalence. PMID- 26131413 TI - Direct Identification of Urinary Tract Pathogens From Urine Samples Using the Vitek MS System Based on Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. AB - BACKGROUND: We evaluated the coincidence rate between Vitek MS system (bioMerieux, France) and Vitek 2 in identifying uropathogens directly from urine specimens. METHODS: Urine specimens submitted to our microbiology laboratory between July and September 2013 for Gram staining and bacterial culture were analyzed. Bacterial identification was performed by using the conventional method. Urine specimens showing a single morphotype by Gram staining were processed by culturing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Of 2,370 urine specimens, 251 showed a single morphotype on Gram staining, and among them, 202 were available for MALDI TOF MS. RESULTS: In these 202 specimens, colony growth was observed in 189 specimens, and 145 specimens had significant growth of single-colony morphotype in culture. One hundred and ten (75.9%) of them had colony counts of >=10(5) colony-forming units (CFU)/mL and included 71 enteric gram-negative bacteria (GNB), 5 glucose-non-fermenting GNB, 9 gram-positive cocci (GPC), and 25 yeasts. Furthermore, 70 (98.6%), 3 (60.0%), 4 (44.4%), and 5 (20.0%), respectively, of these were correctly identified by Vitek MS. Thirty-one specimens (21.4%; 11 GNB, 7 GPC, 12 yeasts, and 1 gram-positive bacillus) had colony counts of 10(4)-10(5) CFU/mL. Four specimens (2.8%) yielded colony counts of 10(3)-10(4) CFU/mL. CONCLUSIONS: Vitek MS showed high rate of accuracy for the identification of GNB in urine specimens (>=10(5) CFU/mL). This could become a rapid and accurate diagnostic method for urinary tract infection caused by GNB. However, for the identification of GPC and yeasts, further studies on appropriate pre-treatment are warranted. PMID- 26131414 TI - Comparison of FcRgamma-Deficient and CD57+ Natural Killer Cells Between Cord Blood and Adult Blood in the Cytomegalovirus-Endemic Korean Population. AB - BACKGROUND: FcRgamma-deficient natural killer (NK) cells (g(-)NK cells) have been associated with cytomegalovirus (CMV) infection. However, the frequency of g(-)NK cells in a CMV-endemic area (i.e., Korea) has not yet been studied. We examined the frequency of g(-)NK cells and expression of CD57 on NK cells in cord blood (CB) and adult blood (AB). METHODS: Of the 24 AB samples collected, 95.8% (23/24) were CMV IgG(+)/IgM(-), while 100% of the 13 healthy CB samples were CMV IgG(+)/IgM(-). We performed whole-blood flow cytometry assays to analyze intracellular FcRgamma and CD3zeta expression of CD3(-)/CD56(dim) NK cells from 13 CB and 24 AB samples, and surface CD57 expression on CD3(-)/CD56(dim)/CD16(+) NK cells from 13 CB and 19 AB samples. RESULTS: All CMV seropositive AB samples contained g(-)NK cells (23/23), and the median proportion of g(-)NK cells in the CD3(-)/CD56(dim) NK cell pool was 35.0% (range: 11-77%). CD57(+) NK cells in the CD3(-)/CD56(dim)/CD16(+) NK cell population were detected in all 19 AB samples tested, but not in any CB samples. CONCLUSIONS: Our data suggest that g(-)NK cells and CD57(+) NK cells are present at a very high frequency in CMV seropositive AB, but rare in CMV-naive CB. PMID- 26131415 TI - Allele and Haplotype Frequencies of Human Leukocyte Antigen-A, -B, -C, -DRB1, and -DQB1 From Sequence-Based DNA Typing Data in Koreans. AB - BACKGROUND: Data on allele frequencies (AFs) and haplotype frequencies (HFs) of HLA-C and -DQB1 are limited in Koreans. We investigated AFs and HFs of HLA-A, -B, -C, -DRB1, and -DQB1 in Koreans by high-resolution sequence-based typing (SBT). METHODS: Hematopoietic stem cells were obtained from 613 healthy, unrelated donors to analyze HLA-A, -B, -C, -DRB1, and -DQB1 genotypes by using AlleleSEQR HLA-A, -B, -C, -DRB1, and -DQB1 SBT kits (Abbott Molecular, USA), respectively. Alleles belonging to HLA-C*07:01/07:06 group were further discriminated by using PCR-sequence specific primer analysis. AFs and HFs were calculated by direct counting and maximum likelihood method, respectively. RESULTS: In all, 24 HLA-A, 46 HLA-B, 24 HLA-C, 29 HLA-DRB1, and 15 HLA-DQB1 alleles were identified. AFs and HFs of HLA-A, -B, and -DRB1 were similar to those reported previously. For the HLA-C locus, C*01:02 was the most common allele, followed by C*03:03, C*03:04, C*14:02, C*03:02, and C*07:02 (AF >=7%). AFs of C*07:01 and C*07:06 were 0.16% and 3.18%, respectively. For the HLA-DQB1 locus, DQB1*03:01 was the most common allele, followed by DQB1*03:03, *03:02, *06:01, *05:01, *04:01, and *06:02 (AF >=7%). AFs of DQB1*02:01 and DQB1*02:02 were 2.12% and 6.69%, respectively. HFs of A*33:03-C*07:06 and C*07:06-B*44:03 were 3.09% and 3.10%, respectively, while those of DRB1*07:01-DQB1*02:02 and DRB1*03:01-DQB1*02:01 were 6.61% and 2.04%, respectively. CONCLUSIONS: This study reported AFs and HFs of HLA, including HLA C and -DQB1, in Koreans by using high-resolution SBT. These data can be used to resolve ambiguous results of HLA typing for organ and hematopoietic stem cell transplantations. PMID- 26131416 TI - Red Blood Cell Transfusion in Patients With Autoantibodies: Is It Effective and Safe Without Increasing Hemolysis Risk? AB - BACKGROUND: The therapeutic efficacy of red blood cell (RBC) transfusions in patients with autoimmune hemolytic anemia (AIHA) is highly debated because of speculations on the increased risk of transfusion reactions; yet it is a suggested adjuvant therapy in anemic patients with life-threatening hypoxemia. In this study, we evaluated the safety and efficacy of RBC transfusions in AIHA patients. METHODS: Daily changes in hemoglobin, total bilirubin, and lactate dehydrogenase (LDH) were assessed in 161 AIHA patients without bleeding history who were transfused once with 1-5 units of the least-incompatible RBCs and monitored over a seven-day period. Post-transfusion patients positive for alloantibodies only or those without RBC-specific antibodies were considered as control groups (N=100 for both groups). RESULTS: The three groups revealed similar increases in hemoglobin of 1.40-1.70 g/dL (autoantibodies), 1.20-1.60 g/dL (alloantibodies only), and 1.40-1.55 g/dL (no antibodies) for seven days following transfusion of 10 mL RBCs/kg. During follow-up, no significant changes in total bilirubin or LDH levels were detected in the AIHA group compared with controls. Influences due to autoantibody type, direct antiglobulin test (DAT) specificity and strength, and steroid therapy status on transfusion reactions were not evident in AIHA patients. In addition, changes in hemoglobin levels were significantly higher (P<0.001) in severe anemia (<5 g/dL) than in other patients. CONCLUSIONS: Transfusion of the least-incompatible RBCs in AIHA patients is effective and safe without any associated increase in hemolysis risk when compared with post-transfusion patients positive for alloantibodies or those lacking RBC-specific antibodies. PMID- 26131417 TI - Evaluation of Modified Formalin-Ether Concentration Method Using Para Tube in Clinical Settings. AB - Conventional formalin-ether concentration method is a gold standard for the diagnosis of parasite infection. However, it may be time-consuming and laborious. We aimed to reveal the clinical usefulness of a modified formalin-ether concentration method using the Para Tube (KS Corporation, Korea) compared with the conventional method. A total of 117 fresh, unpreserved fecal samples composed to 90 negative controls and 27 positive controls with ova of Diphyllobothrium latum/D. nihonkaiense, ova of Clonorchis sinensis and cysts of Giardia lamblia were used in this study. Both methods showed comparable correct identification rate (87.2% for the Para Tube vs. 86.3% for the conventional method).When five samples were examined at once, the Para Tube method reduced the procedure time compared with the conventional method (19 min 58 sec vs. 23 min 18 sec, P=0.0286). We concluded that the modified formalin-ether concentration method using the Para Tube is a rapid, simple, and reliable fecal concentration method for clinical use. PMID- 26131418 TI - Seroepidemiology of Toxocariasis and Its Clinical Implications in Gwangju and Jeonnam-province, Korea. AB - We investigated the seroepidemiological, clinical, and laboratory characteristics of patients suspected to have toxocariasis in Gwangju and Jeonnam-province, Korea. In total, 228 specimens were analyzed for anti-Toxocara canis IgG at two university hospitals from 2010 to 2012. The overall seropositive rate was 67.1%, and the seropositive rates among the eosinophilic and non-eosinophilic groups were 76.1% (105/138) and 53.3% (48/90), respectively. Risk factors for eosinophilia and toxocariasis were male sex (odds ratios [OR]=2.632 and 3.477, respectively) and a history of ingesting raw meat (OR=2.884 and 3.274, respectively), especially raw cow liver (OR=2.089 and 10.038, respectively). T. canis seropositivity (OR=5.807, P=0.004) and a history of consuming raw cow liver (OR=2.766, P=0.052) were risk factors for organ involvement. The anti-T. canis IgG level showed weakly positive correlations with eosinophil counts (r=0.234, P<0.001) and the duration of eosinophilia (r=0.155, P=0.019). Although limited to the regions of Gwangju and Jeonnam-province, this study supports the opinion that toxocariasis is a reasonable focus as a cause of eosinophilia and that it is also associated with organ involvement. PMID- 26131419 TI - Direct Identification of Staphylococcus aureus and Determination of Methicillin Susceptibility From Positive Blood-Culture Bottles in a Bact/ALERT System Using Binax Now S. aureus and PBP2a Tests. AB - Staphylococcus aureus bacteremia is associated with high mortality and morbidity, requiring prompt and appropriate antimicrobial treatment. Therefore, it is important to detect methicillin-resistant S. aureus (MRSA) rapidly from blood cultures. Two immunochromatographic tests, BinaxNow S. aureus and BinaxNow PBP2a, were directly applied to 79 Bact/Alert bottles that were positive for Gram positive cocci in cluster aggregations. Sensitivity and specificity for the identification of S. aureus and determination of methicillin resistance were 94% and 87%, and 100% and 100%, respectively, with less than 30 min of performance time. These tests are efficient and rapid; these tests are valuable alternatives to more sophisticated and expensive methods used in the diagnosis of MRSA bacteremia. PMID- 26131420 TI - Biochemical and Genetic Analysis of Seven Korean Individuals With Suspected Metachromatic Leukodystrophy. AB - Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by a deficiency in arylsulfatase A (ARSA). However, decreased ARSA activity is also observed in pseudodeficiency (PD). To distinguish between MLD and PD, we performed gene mutation and sulfatide analyses by using dried blood spots (DBSs) from seven Korean individuals who underwent an analysis of ARSA activity. DNA was extracted from DBSs, and PCR-direct sequencing of ARSA was performed. The cDNA obtained was analyzed to confirm a novel mutation. Of the seven subjects, three were confirmed as having MLD, one was confirmed as having MLD-PD, one was confirmed as having PD, and the remaining two were obligate heterozygotes. We verified the novel pathogenic variant c.1107+1delG by performing familial and cDNA analyses. Sulfatide concentrations in DBSs were analyzed and were quantified by using ultra-performance liquid chromatography and tandem mass spectrometry, respectively. Total sulfatide concentration was inversely correlated with ARSA activity (Spearman's coefficient of rank correlation, P=0.929, P=0.0025). The results of this mutational and biochemical study on MLD will increase our understanding of the genetic characteristics of MLD in Koreans. PMID- 26131421 TI - Concurrent Hematologic and Metastatic Epithelial Malignancies in the Bone Marrow: Report of Three Cases. PMID- 26131422 TI - An Unusual Case of Myeloperoxidase-Positive Acute Megakaryoblastic Leukemia. PMID- 26131423 TI - Identification of Mixed Lineage Leukemia Gene (MLL)/MLLT10 Fusion Transcripts by Reverse Transcription-PCR and Sequencing in a Case of AML With a FISH-Negative Cryptic MLL Rearrangement. PMID- 26131424 TI - Multidrug-Resistant Corynebacterium striatum Bacteremia: First Case in Korea. PMID- 26131425 TI - Isodicentric Chromosome 15 Syndrome in a Korean Patient With Cafe-au-lait Spots. PMID- 26131426 TI - CrossCheck data of manuscripts submitted to Journal of the Korean Association of Oral and Maxillofacial Surgeons. PMID- 26131427 TI - Effects of fresh mineralized dentin and cementum on socket healing: a preliminary study in dogs. AB - OBJECTIVES: Dentin is composed of many minerals and growth factors. Based on this composition, we studied its effect as a possible regenerative material for alveolar healing. MATERIALS AND METHODS: This study was conducted using four 2.5 year-old mongrel dogs (male; weight, 25 to 30 kg). The third mandibular premolars were carefully mobilized with a dental elevator and then removed using forceps. The crown portions of the extracted teeth were removed with cutters, and the root portions of the remaining teeth were collectively trimmed as closely as possible to 350 to 500 um. Dentin and cementum (DC) chips harvested from the extracted teeth were soaked in blood and packed into the fresh sockets (autograft). Biopsies were performed at the ends of day 14 and day 56 following implantation. Data were expressed as mean+/-standard deviation and compared with t-test results. RESULTS: The ratio of SA(bone) to total area of each probe was determined and was 170+/-16 um(2) for the control group and 71+/-14 um(2) for the DC group, a significant difference (P<0.05). CONCLUSION: DC particulate grafts offered no improvement in bone regeneration in alveolar extraction sockets. PMID- 26131428 TI - Discussion: Effects of fresh mineralized dentin and cementum on socket healing: a preliminary study in dogs. PMID- 26131429 TI - Correlation between clinical symptoms and magnetic resonance imaging findings in patients with temporomandibular joint internal derangement. AB - OBJECTIVES: The purpose of this study was to clarify which findings in magnetic resonance imaging (MRI) are good predicators of pain and mouth opening limitation in patients with temporomandibular joint (TMJ) internal derangement (ID). MATERIALS AND METHODS: Clinical examinations for pain and mouth opening limitation were conducted for suspected TMJ ID. MRI scans were taken within a week of clinical examinations. On the oblique-sagittal plane image, readings were obtained in terms of the functional aspect of disc position, degree of displacement, disc deformity, joint effusion, and osteoarthrosis. Multiple logistic regression analyses were conducted to identify the predictors of pain and mouth opening limitation. RESULTS: A total of 48 patients (96 TMJs) were studied, including 39 female patients and 9 male patients whose ages ranged from 10 to 65 years. The resultant data showed significant correlations between pain and the MR imaging of the degree of disc displacement (P<0.05). The probability of there being pain in moderate to significant cases was 9.69 times higher than in normal cases. No significant correlation was found between mouth opening limitation and MRI findings. CONCLUSION: We identified a significant correlation between clinical symptoms and MRI findings of ID. The degree of anterior disc displacement may be useful for predicting pain in patients with TMJ ID. PMID- 26131430 TI - An in vitro comparison between two different designs of sagittal split ramus osteotomy. AB - OBJECTIVES: To evaluate the influence of the type of osteotomy in the inferior aspect of the mandible on the mechanical performance. MATERIALS AND METHODS: The study was performed on 20 polyurethane hemimandibles. A sagittal split ramus osteotomy (SSRO) was designed in 10 hemimandibles (group 1) with a vertical osteotomy in the buccal side (second molar level) and final osteotomy was performed horizontally on the lingual aspect, while the mandible body osteotomy was finalized as a straight osteotomy in the basilar area, perpendicular to the body. For group 2, the same osteotomy technique was used, but an oblique osteotomy was done in the basilar aspect of the mandibular body, forming continuity with the sagittal cut in the basilar area. Using a surgical guide, osteosynthesis was performed with bicortical screws using an inverted L scheme. In both groups vertical compression tests were performed with a linear load of 1 mm/min on the central fossa of the first molar and tests were done with models made from photoelastic resin. Data were analyzed using Student's t-test, establishing a statistical significance when P <0.05. RESULTS: A statistical difference was not observed in the maximum displacements obtained in the two osteotomies (P <0.05). In the extensiometric analysis, statistically significant differences were identified only in the middle screw of the fixation. The photoelastic resin models showed force dissipation towards the inferior aspect of the mandible in both SSRO models. CONCLUSION: We found that osteotomy of the inferior aspect did not influence the mechanical performance for osteosynthesis with an inverted L system. PMID- 26131431 TI - Odontogenic carcinosarcoma of the mandible: a case report and review. AB - Odontogenic carcinosarcoma is an extremely rare malignant odontogenic tumor with only a few reported cases. It is characterized by a true mixed tumor showing malignant cytology of both epithelial and mesenchymal components. It has been assumed to arise from pre-existing lesions such as ameloblastoma, ameloblastic fibroma, and ameloblastic fibrosarcoma. To date, the reported cases have exhibited considerably aggressive clinical behavior. The case of an odontogenic carcinosarcoma in the mandible of a 61-year-old male is described herein. The tumor destroyed the cortex of the mandible and invaded the adjacent tissues. Treatment was performed by surgical resection and reconstruction. The purposes of this article are to introduce odontogenic carcinosarcoma through this case study, to distinguish it from related diseases and to discuss features of the tumor in the existing literature. PMID- 26131432 TI - Stafne bone cavity and cone-beam computed tomography: a report of two cases. AB - In 1942 Stafne reported 35 asymptomatic, radiolucent cavities that were unilaterally located in the posterior region of the mandible between the mandibular angle and the third molar, and below the mandibular canal. The term Stafne bone cavity (SBC) is now used for such asymptomatic lingual bone depressions of the lower jaw. Since then there have been many reports of SBCs but very fews tudies have used cone-beam computed tomography (CBCT) for their diagnosis. The aim of this paper is to describe the clinical and radiological characteristics of two cases of SBCs and the importance of limited CBCT in confirming the diagnosis. PMID- 26131433 TI - Transmasseteric antero-parotid facelift approach for open reduction and internal fixation of condylar fractures. AB - Surgical approaches to the condylar fracture include intraoral, preauricular, submandibular, and retromandibular approaches. Each approach has its own advantages and disadvantages. When a patient needs esthetic results and an intraoral approach is not feasible, the transmasseteric antero-parotid facelift approach is considered. This approach permits direct exposure and allow the surgeon to fixate the fractured unit tangentially. Tangential fixation is critical to osteosynthesis. Disadvantages of the transmasseteric antero-parotid facelift approach include damage to the facial nerve and a longer operation time. However, after the initial learning curve, facial nerve damage can be avoided and operation time may decrease. We report three cases of subcondylar fractures that were treated with a transmasseteric antero-parotid facelift approach. Among these, two cases had trivial complications that were easily overcome. Instead of dissecting through the parotid gland parenchyma, the transmasseteric antero parotid facelift approach uses transmasseteric dissection and reduces facial nerve damage more than the retromandibular transparotid approach. The esthetic result is superior to that of other approaches. PMID- 26131434 TI - Stability of unilateral sagittal split ramus osteotomy for correction of facial asymmetry: long-term case series and literature review. AB - Bilateral sagittal split ramus osteotomy is considered a standard technique in mandibular orthognathic surgeries to reduce unexpected bilateral stress in the temporomandibular joints. Unilateral sagittal split ramus osteotomy (USSO) was recently introduced to correct facial asymmetry caused by asymmetric mandibular prognathism and has shown favorable outcomes. If unilateral surgery could guarantee long-term postoperative stability as well as favorable results, operation time and the incidence of postoperative complications could be reduced compared to those in bilateral surgery. This report highlights three consecutive cases with long-term follow-up in which USSO was used to correct asymmetric mandibular prognathism. Long-term postoperative changes in the condylar contour and ramus and condylar head length were analyzed using routine radiography and computed tomography. In addition, prior USSO studies were reviewed to outline clear criteria for applying this technique. In conclusion, patients showing functional-type asymmetry with predicted unilateral mandibular movement of less than 7 mm can be considered suitable candidates for USSO-based correction of asymmetric mandibular prognathism with or without maxillary arch surgeries. PMID- 26131435 TI - Screening for variations in anterior digastric musculature prior to correction of post-traumatic anterior open bite by injection of botulinum toxin type A: a technical note. AB - It has recently been reported that long-standing post-traumatic open bite can be successfully corrected with botulinum toxin type A (BTX-A) injection into the anterior belly of the digastric muscle (ABDM). The report documented an individual with bilaterally symmetrical and otherwise unremarkable anterior digastric musculature. However, the existence of variant anterior digastric musculature is common and may complicate the management of anterior open bite with BTX-A injection. Screening for variant ABDM can be accomplished via ultrasound, computed tomography, and magnetic resonance imaging. Screening for variant ABDM should be performed prior to BTX-A injection in order to account for musculature that may exert undesired forces, such as inferolateral deviation, on the anterior mandible in patients with anterior open bite. PMID- 26131436 TI - Consequences of AphanizomenonFlos-aquae(AFA) extract (Stemtech (TM) ) on metabolic profile of patients with type 2 diabetes. AB - BACKGROUND: Blue- green algae is one of the most nutrient dense foods which is rich in substances that have useful effects on human health. The purpose of this study was to evaluate the effectiveness of a water- soluble extract of the cyanophyta Aphanizomenon Flos-aquae (Stemtech (TM) ) as a functional supplement on CD markers, lipid profile, glucose levels as well as its side effects in Iranian patients with type 2 diabetes. METHODS: During this randomized, double blind, placebo-controlled trial 49 type 2 diabetic patients, aged between 20 and 60 years with a HbA1C >= 7.5 %, were allocated. Patients were divided into two groups of placebo and treated with an equal ratio 1:1. The subjects in StemtechTM group received one capsule of StemFlo (508 mg) before breakfast and two capsules of StemEnhance (500 mg) after each meal for a period of 12 weeks, and placebo group was instructed to take placebo with the same pattern. During the intervention period, subjects were asked to keep usual diet and prohibited to take any functional foods or dietary supplements. Metabolic panel has been measured as the primary outcome of study at the beginning and end of the intervention period via blood sampling. RESULTS: Stemtech (TM) supplementation for 12 weeks decreased fasting blood glucose (FBG) and Glycatedhemoglobin (HbA1c). Mean serum chemistry parameters (Triglyceride, Total Cholesterol, LDL, HDL, CRP, AST, ALT, BUN and Creatinine) as well as CD 34(+), IL-6, TNF-alpha in treated and control groups before and after the study showed no considerable dissimilarities. CONCLUSION: StemtechTM intervention brought in positive consequence on blood glucose levels in Iranian patients with type 2 diabetes, consequently suggests the Stemtech (TM) as a functional food for the management of diabetes. PMID- 26131437 TI - Prevalence of vitamin D deficiency across the spectrum of glucose intolerance. AB - BACKGROUND: Vitamin D deficiency (VDD) is inversely associated with insulin resistance. We studied the prevalence of VDD across the spectrum of glucose intolerance, including normal glucose tolerance (NGT), prediabetes (PD) and type 2 diabetes (T2D). METHODS: We conducted this cross-sectional, observational study by serially including the PD and T2D patients seen between June and December 2014. We excluded patients with major illness, secondary diabetes and use of vitamin D or glucocorticoids. VDD was defined as serum 25-hydroxy vitamin D (25OHD) less than 30 ng/mL. The study population was divided into 3 groups: T2D (Group 1; n = 274), PD (Group 2; n = 62) and NGT controls (Group 3; n = 270) for the analysis and appropriate statistical methods were used. RESULTS: The study participants (n = 606, 28 % males) had a mean age of 43.2 +/- 13.6 years, BMI of 27.7 +/- 5.9 kg/m(2), HbA1c of 6.6 +/- 2 % and mean 25OHD of 18.8 +/- 15.7 ng/mL. VDD was seen in 85 % of the entire study population including 84 % in T2D, 77 % in prediabetes and in 87 % of the controls. The mean 25OHD levels were lower in the control group (16.8 ng/mL) when compared with T2D and prediabetes (19.9 and 22.4 ng/mL) respectively (P = 0.0124). Univariate analysis showed higher odds of VDD in females (P < 0.0001) but no association with diabetes, age, BMI and HbA1c. CONCLUSION: Our data showed that VDD is prevalent in the majority of the population, irrespective of the underlying glucose intolerance. Further studies are required to determine the association between the vitamin D and diabetes. PMID- 26131439 TI - CD44 expression in patients with combined hepatocellular cholangiocarcinoma. AB - PURPOSE: Combined hepatocellular cholangiocarcinoma (ChC) is a rare type of primary liver cancer, which is thought to have a poorer prognosis than hepatocellular carcinoma (HCC). Cancer stem cells are associated with tumorigenesis, tumor progression, recurrence, metastasis, and poor prognosis in several malignancies including HCC. The aim of this study was to investigate the expression pattern of cancer stem cell markers in ChC and HCC, and to evaluate whether this pattern correlated to patient prognosis. METHODS: Thirteen patients who underwent curative hepatic resection for ChC and 13 patients who underwent curative hepatic resection for HCC (matched control cases) were included. Immunohistochemical staining for cancer stem cell markers (cytokeratin [CK]7, CK19, C-kit, cluster of differentiation [CD] 44, CD133, and epithelial cell adhesion molecule) was performed and clinical outcomes were analyzed retrospectively. RESULTS: There was no significant difference in cancer stem cell marker expression between ChC and HCC. In ChC, the group that expressed CD44 showed earlier recurrence than the group that did not express CD44 (P = 0.040). CONCLUSION: The expression of cancer stem cell markers in ChC did not show a different pattern compared to that found in HCC. The expression of cancer stem cell marker CD44 was associated with poor prognosis in patients with ChC. PMID- 26131438 TI - Pivotal role of vascular endothelial growth factor pathway in tumor angiogenesis. AB - The shaping of new blood vessels is a significant event in cancer growth and metastasis. Therefore, the molecular system of cancer angiogenesis has garnered considerable interest in cancer research. The vascular endothelial growth factor (VEGF) and VEGF receptor pathway are recognized as the key regulators of the angiogenic process. Activation of the VEGF/VEGF-receptor pathway initiates signaling cascades that promote endothelial cell growth, migration, and differentiation. Recently, VEGF was shown to play a role in the recruitment of bone marrow-derived endothelial progenitor cells to neovascularization sites. The role of VEGF in promoting tumor angiogenesis and the occurrence of human cancers has led to the rational design and development of agents that selectively target this pathway. Moreover, these anti-VEGF/VEGF receptor agents show therapeutic potential by inhibition of angiogenesis and tumor growth in preclinical models. In this review, we summarize the role of the VEGF pathway during tumor angiogenesis. PMID- 26131440 TI - The effects of ventilation with high density oxygen on the strength of gastrointestinal anastomosis. AB - PURPOSE: The aim of our study is to evaluate the effects of administration of perioperative supplemental oxygen on anastomoses. METHODS: Forty male Wistar albino rats were used in the study and randomized into 4 groups. Ischemia reperfusion models were built in groups 3 and 4. Jejunojejunostomy was performed in all rats and assigned to an oxygen/nitrous oxide mixture with a fraction of inspired oxygen of 30% in groups 1 and 3 and 80% in groups 2 and 4. The measurements of perianastomotic tissue oxygen pressure, bursting pressure, level of hydroxyproline were evaluated and compared in all groups. RESULTS: The perianastomotic tissue oxygen pressures, bursting pressures and levels of hydroxyproline were identified as significantly high in groups 2 and 4, administered a fraction of inspired oxygen of 80%, compared to groups 1 and 3, administered a fraction of inspired oxygen of 30%. CONCLUSION: Perioperative supplemental oxygen contributes positively to the anastomotic healing. PMID- 26131441 TI - Oncologic outcomes in rectal cancer with close distal resection margins: a retrospective analysis. AB - PURPOSE: The assurance of a negative resection margin is significant in rectal cancer as it indicates a reduced risk of local recurrence; thus, sufficient length of the resection margin is strongly required. The purpose of this study was to analyze the relationship between the length of the distal resection margin (DRM) and local recurrence or survival rate and to evaluate the possibility of performing sphincter-conserving surgery. METHODS: The medical records of 218 rectal cancer patients were analyzed. Patients were classified into three groups according to the length of the DRM as follows: group 1, DRM < 1 cm; group 2, 1 cm <= DRM <= 2 cm; and group 3, DRM > 2 cm. RESULTS: Of 218 patients enrolled, 81 were in group 1, 66 in group 2, and 71 in group 3. The 5-year survival rates were 78.2%, 78.2%, and 76.8% for groups 1, 2, and 3, respectively, and there were no statistically significant differences in survival (P = 0.913). Local recurrence was found in 2 patients in group 1, 1 patient in group 2, and 1 patient in group 3; there were no statistically significant differences in local recurrence (P = 0.908). CONCLUSION: A DRM of < 1 cm did not impair the oncologic outcomes of rectal cancer patients. Our results indicated that surgeons should keep in mind to consider the option of sphincter-conserving surgery with adjuvant chemoradiotherapy even in very low rectal cancer. PMID- 26131442 TI - Outcomes of retrievable inferior vena cava filters in patients with deep vein thrombosis and transient contraindication for anticoagulation. AB - PURPOSE: To determine the efficacy of a retrievable inferior vena cava filter (IVCF) for patients with deep vein thrombosis (DVT) and transient contraindication for anticoagulant therapy, and to analyze the risk factors for filter thrombus in these patients. METHODS: We retrospectively reviewed the records of 70 patients who received a retrievable IVCF from January 2007 to June 2014 because of documented DVT and transient contraindication for anticoagulant therapy. The protocol for follow-up care generally consisted of anticoagulant therapy after high-risk periods, follow-up CT around 2 weeks after IVCF placement, and retrieval if possible. RESULTS: The 70 patients had a mean age of 61.8 years (range, 17-88 years), and 30 were male (43%). The indications for IVCF were recent trauma including surgery in 48 patients, recent hemorrhage in 14, and planned major surgery with DVT in 8 patients. Follow-up CT of 61 patients (87%) was performed. Aggravation or new development of pulmonary embolism (PE) was not found in any patient. Filter thrombus was detected in 23% of patients with follow up CT (14/61). Filter thrombus was not detected in patients with isolated calf vein thrombosis (ICVT) (P = 0.079). The risk factor for filter thrombus was DVT progression on follow-up CT (P = 0.007) on multivariate analysis. CONCLUSION: For patients with DVT and transient contraindication for anticoagulant therapy, a retrievable IVCF could prevent the aggravation or new development of PE. DVT progression on follow-up CT was associated with filter thrombus and ICVT was not related to filter thrombus in the present study. PMID- 26131443 TI - Heterogeneous living donor hepatic fat distribution on MRI chemical shift imaging. AB - PURPOSE: We evaluated the heterogeneity of steatosis in living donor livers to determine its regional differences. METHODS: Between June 2011 and February 2012, 81 liver donors were selected. Fat fraction was estimated using magnetic resonance triple-echo chemical shifting gradient imaging in 13 different regions: segment 1 (S1), S2, S3, and each peripheral and deep region of S4, S5, S6, S7, and S8. RESULTS: There were differences (range, 3.2%-5.3%) in fat fractions between each peripheral and deep region of S4, S6, S7, and S8 (P < 0.001, P = 0.004, P < 0.001, and P = 0.006). Fat deposit amount in S1, S2, S3 and deep regions of S4-S8 were significantly different from one another (F [4.003, 58.032] = 8.684, P < 0.001), while there were no differences among the peripheral regions of S4-S8 (F [2.9, 5.3] = 1.3, P = 0.272) by repeated measure analysis of variance method. And regional differences of the amount of fat deposit in the whole liver increased as a peripheral fat fraction of S5 increased (R(2) = 0.428, P < 0.001). CONCLUSION: Multifocal fat measurements for the whole liver are needed because a small regional evaluation might not represent the remaining liver completely, especially in patients with severe hepatic steatosis. PMID- 26131444 TI - Clinical characteristics of ceftriaxone plus metronidazole in complicated intra abdominal infection. AB - PURPOSE: Empirical antibiotics in complicated intra-abdominal infection (c-IAI), such as secondary peritonitis are a first step of treatment. Empirical antibiotic regimen is very diverse. Ceftriaxone plus metronidazole regimen (CMR) is one of the empirical antibiotic regimens used in treatment of c-IAI. However, although CMR is a widely used empirical antibiotic regimen, study regarding success, failure or efficacy of CMR has been poorly understood. This retrospective study is conducted to compare the clinical efficacy of this regimen in c-IAI according to clinical characteristics. METHODS: The subjects were patients in this hospital who were diagnosed as secondary peritonitis between 2009 and 2013. Retrospective analysis was performed based on the records made after surgery regarding clinical characteristics including albumin level, blood pressure, pulse rate, respiration rate, smoking, age, sex, body mass index, hemoglobin, coexisting disease, leukocytosis, and APACHE (acute physiology and chronic health evaluation) II score. RESULTS: A total of 114 patients were enrolled. In univariated analysis, the success and failure of CMR showed significant association with preoperative low albumin, old age, and preoperative tachycardia. In multivariated analysis, low albumin and preoperative tachycardia were significant. CONCLUSION: It is thought that an additional antibiotic treatment plan is necessary in patients with low albumin and tachycardia when the empirical antibiotic regimen is CMR in c-IAI. Conduct of research through well-designed prospective randomized clinical study is also necessary in order to evaluate the appropriateness of CMR and decide on a proper empirical antibiotic regimen between many regimens in c-IAI based on our country. PMID- 26131445 TI - Renal autotransplantation in open surgical repair of suprarenal abdominal aortic aneurysm. AB - Although the standard treatment of abdominal aortic aneurysm has shifted from open surgery to endovascular repair, open surgery has remained the standard of care for complex aneurysms involving the visceral arteries and in patients unsuitable for endovascular aneurysm repair. Postoperative renal insufficiency may occur after open surgical repair of suprarenal abdominal aortic aneurysm. Methods of minimizing renal ischemic injury include aortic cross-clamping and renal reconstruction techniques. This report describes the use of renal autotransplantation for renal reconstruction during open surgical repair of a suprarenal abdominal aortic aneurysm. This technique was successful, suggesting its feasibility for open suprarenal abdominal aortic aneurysm repair, minimizing renal ischemic injury and optimizing postoperative renal function. PMID- 26131446 TI - Use of cryopreserved cadaveric arterial allograft as a vascular conduit for peripheral arterial graft infection. AB - Major peripheral arterial graft infection is a potentially devastating complication of vascular surgery, associated with significant mortality and high amputation rates. Autologous saphenous veins are considered optimal arterial conduits for lower extremity revascularization in infected fields, but they are often unavailable or unsuitable in these patients. This study describes two patients with major peripheral graft infection, but without available autologous veins, who underwent graft excision and cryopreserved cadaveric arterial allograft reconstruction. Although long-term graft durability is unclear because of gradual deterioration and degeneration, these findings suggest that cadaveric allografts may be good options for patients with major peripheral graft infection. PMID- 26131447 TI - NK Cell Inflammation in the Clinical Outcome of Colorectal Carcinoma. AB - The ability of natural killer (NK) cells to provide protection against myeloid leukemia has been demonstrated in clinical settings. However, whether NK cells play a role in the clinical course of solid tumors is debated. The controversy surrounding the role of NK cells is due, at least in part, to the limited extent of NK cell infiltration found in the tumor bed. Inactivation of NK cells may explain the shortage of NK cells in the microenvironment of colorectal cancer (CRC). Upon NK cell/tumor cell interaction, tumor cells may escape NK cells by creating an immunosuppressive microenvironment, which possibly affects T-cells as well. Such an immunosuppressive microenvironment would hamper the functions of NK and T-cell and reduce NK and T-cell interactions. CRC patients with levels of tumor NK cell infiltration suitable for statistical analysis have been identified. The infiltration of the CRC microenvironment by NK cells, in combination with CD8(+) T-lymphocytes, has been shown to enhance the prognosis of CRC patients. Here, we discuss the clinicopathological role of NK cells in CRC, and present clinical data indicating a potential supporting role for NK cells in the anti-CRC effects of CD8(+) T-cells. PMID- 26131448 TI - Current Animal Models of Postoperative Spine Infection and Potential Future Advances. AB - Implant related infection following spine surgery is a devastating complication for patients and can potentially lead to significant neurological compromise, disability, morbidity, and even mortality. This paper provides an overview of the existing animal models of postoperative spine infection and highlights the strengths and weaknesses of each model. In addition, there is discussion regarding potential modifications to these animal models to better evaluate preventative and treatment strategies for this challenging complication. Current models are effective in simulating surgical procedures but fail to evaluate infection longitudinally using multiple techniques. Potential future modifications to these models include using advanced imaging technologies to evaluate infection, use of bioluminescent bacterial species, and testing of novel treatment strategies against multiple bacterial strains. There is potential to establish a postoperative spine infection model using smaller animals, such as mice, as these would be a more cost-effective screening tool for potential therapeutic interventions. PMID- 26131449 TI - Updates on Functional Characterization of Bronchopulmonary Dysplasia - The Contribution of Lung Function Testing. AB - Bronchopulmonary dysplasia (BPD) is a chronic lung disease that predominantly affects prematurely born infants. Initially, BPD was described in infants who had suffered severe respiratory failure and required high pressure, mechanical ventilation with high concentrations of supplementary oxygen. Now, it also occurs in very prematurely born infants who initially had minimal or even no signs of lung disease. These differences impact the nature of the lung function abnormalities suffered by "BPD" infants, which are also influenced by the criteria used to diagnose BPD and the oxygen saturation level used to determine the supplementary oxygen requirement. Key also to interpreting lung function data in this population is whether appropriate lung function tests have been used and in an adequately sized population to make meaningful conclusions. It should also be emphasized that BPD is a poor predictor of long-term respiratory morbidity. Bearing in mind those caveats, studies have consistently demonstrated that infants who develop BPD have low compliance and functional residual capacities and raised resistances in the neonatal period. There is, however, no agreement with regard to which early lung function measurement predicts the development of BPD, likely reflecting different techniques were used in different populations in often underpowered studies. During infancy, lung function generally improves, but importantly airflow limitation persists and small airway function appears to decline. Improvements in lung function following administration of diuretics or bronchodilators have not translated into long-term improvements in respiratory outcomes. By contrast, early differences in lung function related to different ventilation modes have led to investigation and demonstration that prophylactic, neonatal high-frequency oscillation appears to protect small airway function. PMID- 26131451 TI - One-Step Nucleic Acid Amplification in Breast Cancer Sentinel Lymph Node: A Single Institutional Experience and a Short Review. AB - Sentinel lymph node (SLN) examination is a standard in breast cancer patients, with several methods employed along its 20 years history, the last one represented by one-step nucleic acid amplification (OSNA). The latter is a intra operative molecular assay searching for CK19 mRNA as a surrogate of metastatic cells. Our 3 years experience with OSNA (1122 patients) showed results overlapping those recorded in the same institution with a morphological evaluation (930 patients) of SLN. In detail, the data of OSNA were almost identical to those observed with standard post-operative procedure in terms of patients with positive SLN (30%) and micrometastatic/macrometastatic involvement of SLN (respectively, 38-45 and 62-55%). By contrast, when OSNA was compared to the standard intraoperatory procedure, it was superior in terms of accuracy, prompting the use of this molecular assay as a very valid, and reproducible for intra-operative evaluation of SLN. Further possibilities prompting the use of OSNA range from adhesion to quality control programs, saving of medical time, ability to predict, during surgery, additional nodal metastasis, and molecular bio-banking. PMID- 26131452 TI - Metabolomic investigation of systemic manifestations associated with Alzheimer's disease in the APP/PS1 transgenic mouse model. AB - There is growing evidence that Alzheimer's disease may be a widespread systemic disorder, so peripheral organs could be affected by pathological mechanisms occurring in this neurodegenerative disease. For this reason, a double metabolomic platform based on the combination of gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-mass spectrometry was used for the first time to investigate metabolic changes in liver and kidney from the transgenic mice APP/PS1 against wild-type controls. Multivariate statistics showed significant differences in levels of numerous metabolites including phospholipids, sphingolipids, acylcarnitines, steroids, amino acids and other compounds, which denotes that multiple pathways might be associated with systemic pathogenesis of Alzheimer's in this mouse model, such as bioenergetic failures, oxidative stress, altered metabolism of membrane lipids, hyperammonemia or impaired homeostasis of steroids. Furthermore, it is noteworthy that some novel pathological mechanisms were found, such as impaired gluconeogenesis, polyol pathway or metabolism of branched chain amino acids, not previously described for Alzheimer's disease. Therefore, these findings clearly support the hypothesis that Alzheimer's disease may be considered as a systemic disorder. PMID- 26131450 TI - Non-Coding RNAs in Primary Liver Cancer. AB - Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with poor prognosis and limited therapeutic options. Over the past few years, many studies have evaluated the role of non-coding RNAs (ncRNAs) in hepatocarcinogenesis and tumor progression. ncRNAs were shown to have diagnostic, prognostic, and therapeutic potential in HCC. In this manuscript, we review the latest major discoveries concerning microRNAs and long ncRNAs in HCC pathogenesis, and discuss the potentials and the limitations for their use in clinical practice. PMID- 26131453 TI - How useful is molecular modelling in combination with ion mobility mass spectrometry for 'small molecule' ion mobility collision cross-sections? AB - Ion mobility mass spectrometry is used to measure the drift-time of an ion. The drift-time of an ion can be used to calculate the collision cross-section (CCS) in travelling wave ion mobility (e.g. Waters Synapt and Vion instruments) or directly determine the experimental CCS (e.g. Agilent 6560 instrument and many drift-tube instruments). A comparison of the experimental CCS and theoretical CCS values obtained from trajectory method He(g) parameterised MOBCAL and N2(g) parameterised MOBCAL software, for a range of 20 'small molecules' is presented. This study utilises density functional theory B3LYP methods and the 6-31G+(d,p) basis set to calculate theoretical CCS values. This study seeks to assess the accuracy of a common procedure using CCS calibration with poly-(d/l)-alanine derived from drift-cell measurements and the original release of MOBCAL software and compare it with recent improvements with a drug-like molecule calibration set and a revision of MOBCAL parameterised for N2(g) drift gas. This study represents one of the first quantitative evaluations of the agreement between theoretical CCS and experimental CCS values for a range of small pharmaceutically relevant molecules using travelling wave ion mobility mass spectrometry. Accurate theoretical CCS may allow optimisation of ion mobility separations in silico, provide CCS databases that can confirm structures without the need for alternative analytical tools such as nuclear magnetic resonance spectroscopy (NMR) and assignment of unknowns and positional isomers without requiring reference materials. PMID- 26131454 TI - Chip-based array magnetic solid phase microextraction on-line coupled with inductively coupled plasma mass spectrometry for the determination of trace heavy metals in cells. AB - Determination of trace elements in cells is critical to metallomics research and still faces tremendous difficulties even with the help of highly sensitive inductively coupled plasma mass spectrometry (ICP-MS). Microfluidic chips offer a functional tool-set for cell analysis with features of miniaturization, integration and automation. In this work, we proposed a chip-based array magnetic solid phase microextraction (MSPME) system and on-line combined it with ICP-MS via microflow concentric nebulization for the determination of trace Cu, Zn, Cd, Hg, Pb and Bi in cells. Under the optimized conditions, the limits of detection of the developed on-line chip-based array MSPME-ICP-MS system are 49, 43, 4.2, 6.1, 13 and 18 ng L(-1) for Cu, Zn, Cd, Hg, Pb and Bi, respectively. The proposed method was applied to the analysis of target heavy metals in three kinds of cells (HepG2, Jurkat T and MCF7), and the recoveries for the spiked samples were in the range of 83.8%-117%. The extractable species of the target metals in cells were also studied and the results demonstrated a high selectivity of the developed methods towards free metal ions and/or their small molecular species. PMID- 26131455 TI - Guest Editorial--ISCAS 2014 Special Issue. PMID- 26131457 TI - Rheumatoid arthritis in the Kingdom of Saudi Arabia. Reply from the Author. PMID- 26131458 TI - The effects of probiotics on the treatment of Helicobacter pylori eradication in children. Reply from the Author. PMID- 26131456 TI - Coronary artery calcifications predict long term cardiovascular events in non diabetic Caucasian hemodialysis patients. AB - Vascular calcifications are frequent in chronic renal disease and are associated to significant cardiovascular morbidity and mortality. The long term predictive value of coronary artery calcifications detected by multi-layer spiral computed tomography for major cardiovascular events was evaluated in non-diabetic Caucasian patients on maintenance hemodialysis free of clinical cardiovascular disease. Two-hundred and five patients on maintenance hemodialysis were enrolled into this observational, prospective cohort study. Patients underwent a single cardiac multi-layer spiral computed tomography. Calcium load was quantified and patients grouped according to the Agatston score: group 1 (Agatston score: 0), group 2 (Agatston score 1-400), group 3 (Agatston score 401-1000) and group 4 (Agatston score >1000). Follow-up was longer than seven years. Primary endpoint was death from a major cardiovascular event. Actuarial survival was calculated separately in the four groups with Kaplan-Meier method. Patients who died from causes other than cardiovascular disease and transplanted patients were censored. The "log rank" test was employed to compare survival curves. One-hundred two patients (49.7%) died for a major cardiovascular event during the follow-up period. Seven-year actuarial survival was more than 90% for groups 1 and 2, but failed to about 50% for group 3 and to <10% for group 4. Hence, Agatston score >400 predicts a significantly higher cardiovascular mortality compared with Agatston score <400 (p<0.0001); furthermore, serum Parathyroid hormone levels > 300 pg/l were associated to a lower survival (p < 0.05). Extended coronary artery calcifications detected by cardiac multi-layer spiral computed tomography, strongly predicted long term cardiovascular mortality in nondiabetic Caucasian patients on maintenance hemodialysis. Moreover, it was not related to conventional indices of atherosclerosis, but to other non-traditional risk factors, as serum Parathyroid hormone levels. A full cost-benefit analysis is however necessary to justify a widespread use of cardiac multi-layer spiral computed tomography in clinical practice. PMID- 26131459 TI - Urgency to rein in the gene-editing technology. PMID- 26131460 TI - Author response. PMID- 26131461 TI - Author response. PMID- 26131462 TI - New species of Terebellides (Polychaeta: Trichobranchidae) from the deep Southern Ocean, with a key to all described species. AB - The genus Terebellides is, despite its often low abundances, a common and diverse element of benthic, soft sediment communities at all depths. In recent years, careful examination of specimens has resulted in numerous descriptions of new species of Terebellides increasing the number of species in the genus to over forty. For the Southern Ocean currently only two species are considered valid, both recorded for shelf and slope depths. Here, we present findings of eleven new Antarctic species originating from depths between 480 m and 4720 m. Six of these are formally described (T. canopus sp. n., T. crux sp.n., T. mira sp.n., T. rigel sp.n., T. sirius sp.n., and T. toliman, sp.n.). One species, T. crux sp.n., bears two segments with geniculate hooks, a trait already known for the genus but conflicting with the original generic diagnosis. To include this trait the generic diagnosis of Terebellides is amended. An identification key for all species of Terebellides is given, as well as a maximum parsimony phylogeny of the genus based on morphological characters. PMID- 26131463 TI - The reptile type specimens preserved in the Museo Nacional de Ciencias Naturales (CSIC) of Madrid, Spain. AB - A first complete list of the reptile type specimens preserved in the Museo Nacional de Ciencias Naturales (CSIC) of Madrid (updated until 15 July 2012) is provided. The collection houses a total of 319 type specimens representing 24 taxa belonging to 6 families and 12 genera. There are 22 taxa represented by primary types (19 holotypes, 2 neotypes and 1lectotype) and at least one paratype, and only two taxa are exclusively represented by one secondary type (paratype). The collection is specially rich in Spanish endemisms. Special attention is deserved by the type series of many subspecies of Podarcis lilfordi described by A. Salvador and V. Pdeez-Mellado. All type specimens are housed in the Herpetological collection except Blanus mariae and Psaimodroims occidentalis type series and Psammodroims hispanicus (neotype) which are preserved in the DNA/Tissues Collection. PMID- 26131465 TI - A new Hydrometra ( Hemiptera: Heteroptera: Hydrometridae) from northeastern Brazil, with a key to the species recorded from the country. AB - Hydrometra sapiranga sp. nov. is described, illustrated, and compared with similar species. An identification key to the species of Hydrometra recorded from Brazil is also presented. PMID- 26131464 TI - Deep Divergences within Liolaemus nigroviridis (Squamata, Liolaemidae) Lineages Associated with Sky Islands in Central Chile. AB - Evolution of montane species may be strongly influenced by climate oscillations, particularly species distributed in isolated high-elevation areas (sky islands). Chilean topography is exemplified by montane environments including the Andes and Coastal Mountains. To test hypotheses related to genetic divergence associated with sky islands, we explored population genetics and phylogenetic signatures in the montane lizard Liolaemus nigroviridis Muller and Hellmich 1932. We sequenced the mitochondrial cytochrome b for samples collected from six montane areas in central Chile. We found high genetic divergence among populations, congruent with well-supported clades from phylogeny reconstructions. The most recent common ancestor of all samples of L. nigroviridis was dated around the limit of Pliocene Pleistocene (2.7 Mya), congruent with early vicariance of Andean and coastal populations. Deep lineage divergences suggest that allopatric populations accumulated high nucleotide differences and maintained long periods without gene exchange. We discuss potential taxonomic revisions considering relative genetic divergence. PMID- 26131466 TI - Enderleina khazeni n. sp. (Plecoptera, Perlidae), a new stonefly from Venezuelan Guayana. AB - A new species of Enderleina (Plecoptera), E. khazeni n. sp., is described from two males collected in Bolivar Province, Southeast Venezuela. It appears to be more closely related to E. preclara Jewett that to other Enderleina species, but can be clearly distinguished from that species by shape of the penial sclerites. With the description of this new taxon, six species of the genus are known, of these males of four of them have been described. PMID- 26131467 TI - Chrysomelid males with enlarged mandibles: three new species and a review of occurrence in the family (Coleoptera: Chrysomelidae). AB - Three new species of Chrysomelidae with extraordinary extensions of the male mandibles are described: Scaphodius drehu sp. nov. and S. ferox sp. nov. (Cryptocephalinae), from New Caledonia, and Chaloenus gajah sp. nov. (Galerucinae), from Borneo. Designation of the type species of Chaloenus Westwood, 1861, is clarified. Synonymy of Scaphodius Chapuis, 1874, with Nyetra Baly, 1877, is supported. Four species of Ditropidus Erichson, 1842, described from New Caledonia, but hitherto regarded as nomina nuda, are shown to be available and are placed in Scaphodius: S. aeneus (Fauvel, 1907), comb. nov., S. nitidus (Fauvel, 1907) comb. nov., S. striolatus (Fauvel, 1907) comb. nov., S. sulcatus (Fauvel, 1907) comb. nov. Ditropidus opacicollis Fauvel, 1907, is also transferred to Scaphodius, as S. opacicollis (Fauvel) comb. nov. The genus Ditropidus does not occur on New Caledonia. Male mandible enlargment in the Chrysomelidae is reviewed: it is common in Cryptocephalinae, but otherwise restricted to a few species of Chrysomelinae, Eumolpinae and Galerucinae. Possible reasons for its distribution in the Chrysomelidae are discussed. PMID- 26131468 TI - Four new species of Gracillariidae (Lepidoptera) from China and Japan, and description of the pupal morphology of the genera Corythoxestis, Eumetriochroa, Guttigera, and Metriochroa. AB - Four new leaf mining Oecophyllembiinae (Gracillariidae) species are described from China and Japan: Metriochroa symplocosella sp. nov. (host plants: Symplocos anomala, S. sumuntia, Symplocaceae) from China, Guttigera schefflerella sp. nov. (host plant: Schefflera octophylla, Araliaceae), Eumetriochroa araliella sp. nov. (host plants: Dendropanax trifidus, Evodiopanax innovans, Eleutherococcus sciadophylloides and Fatsia japonica, Araliaceae) and Corythoxestis tricalysiella sp. nov. (host plant: Tricalysia dubia, Rubiaceae) from Japan. Corythoxestis sunosei (Kumata, 1998) is recorded from new host plants: Adinapilulifera and Mussaenda parviflora, Rubiaceae, from Japan. The female adult and pupal morphologies, life history and host plant of the genus Guttigera are described for the first time. Pupae of seven species of four genera: Corythoxestis, Eumetriochroa, Guttigera, and Metriochroa, are described for the first time. We provide morphological diagnostic differences between species and genera of Oecophyllembiinae and Phyllocnistis. Our preliminary data suggest that Oecophyllembiinae species have three valuable pupal diagnostic characters: 1) cocoon cutter with unique lateral processes or setae on the clypeus, 2) tergal spines with only a pair of dorsal setae, and 3) cremaster with more than two pairs of caudal processes, while Phyllocnistis species possess 1) cocoon cutter without lateral processes or setae on clypeus, 2) tergal spines with a pair of dorsal setae and dorsal hooks, and 3) cremaster with only a pair of caudal processes. PMID- 26131469 TI - Two new species of cascudinhos of the genus Otothyropsis (Siluriformes: Hypoptopomatinae) from the rio Parana basin, Brazil. AB - Otothyropsis polyodon, sp. n., and O. biamnicus, sp. n., two new species of loricariid catfishes are described from the rio Parana basin. Otothyropsis biamnicus and O. polyodon differ from two other Otothyropsis by having a longer caudal peduncle, middle series of lateral plates complete and with higher number of plates, and the anterior margin of the mesethmoid not covered by median rostral plate ventrally. The new species differ from each other in that O. polyodon have a longer pectoral-fin spine and a greater number of premaxillary and dentary teeth. Otothyropsis polyodon was collected in the rio Verde, tributary to the upper rio Parana basin, and O. biamnicus is found in both the rio Iguacu and rio Tibagi basins. A key for the species of Otothyropsis is presented and their relationships and geographical distributions are discussed. PMID- 26131470 TI - The Norwegian species of Copidosoma Ratzeburg (Hymenoptera: Chalcidoidea: Encyrtidae). AB - The species of Copidosoma Ratzeburg (Hymenoptera: Encyrtidae) are reviewed for Norway. Sixteen species are recognized, of which one, Copidosoma longicaudata sp. nov., is newly described, illustrated and compared with closely related species. Seven species represent new distribution records for Norway--C. aithyia (Walker), C. genale (Thomson), C. herbaceum Mercet, C. primulum (Mercet), C. radnense Erdos, C. thebe (Walker) and C. truncatellum (Dalman). An illustrated dichotomous key for the identification of both sexes of Norwegian Copidosoma is presented. PMID- 26131471 TI - Cerchysiella mesosae Yang sp. nov. (Hymenoptera: Encyrtidae), a parasitoid of Mesosa myops (Dalman) (Coleoptera: Cerambycidae) larvae in China. AB - Cerchysiella mesosae Yang sp. nov. (Hymenoptera: Chalcidoidea: Encyrtidae), is described from China. It is a gregarious koinobiont endoparasitoid in mature larvae of Mesosa myops (Dalman) (Coleoptera: Cerambycidae), a wood boring pest of many broad-leaved tree species in China, particularly Quercus mongolica and Q. liaotungensis (Fagaceae) in forest areas of northeastern China. The new species is one of the principal natural enemies of the wood borer and it may have potential as a biological control agent for suppression of the pest. PMID- 26131472 TI - Revision of the Chinese Geotragus Schoenherr with description of three new species (Coleoptera: Curculionidae: Entiminae). AB - The Chinese representatives of the entimine weevil genus Geotragus are here revised, including redescriptions of the two previously known species, G. himalayanus Boheman, 1845 and G tuberculatus Chen, 1990, and descriptions of three new species from the Hengduan Mountains, Yunnan province, China: G. brevidens sp. nov., G. declivis sp. nov. and G. rugosus sp. nov.. Diagnostic characters of the genus, a key to Chinese species of Geotragus and a checklist of the now 11 known world species are also provided. PMID- 26131473 TI - New species of the genus Colobostema Enderlein (Diptera: Scatopsidae) from Mexico. AB - Five new species of the genus Colobostema Enderlein, 1926 from Mexico are described and illustrated: C. emilianoi (Chiapas), C. marielae (San Luis Potosi), C. valentinae (Jalisco), C. lupitae (Oaxaca) and C. marlettae (Yucatan). A key to the males of Neotropical species of Colobostema is provided. The male genitalia structures (especially the vestiture of parameres and the shape of tergite 9) indicates that all these new species form a group of closely related taxa, associated to the species of the Nearctic and Neotropical region. PMID- 26131474 TI - A new species of Megarhyssa Ashmead (Hymenoptera: Ichneumonidae: Rhyssinae) from tropical Mexico with a key to Mexican species. AB - A new species of ichneumon wasp, Megarhyssa gratiosa sp. nov., is described from Chiapas province in the tropical part of Mexico. This is a southern most record of the genus in the New World. The new species is one of the largest and most spectacular ichneumonid species in the Mexican fauna. Megarhyssa gratiosa sp. nov. differs from its North American congeners primarily by the conspicuous colour pattern of the metasoma which is yellow with broad dorsal black stripe extending along its entire length, and the longer ovipositor. A key to three Mexican species of Megarhyssa is also provided. PMID- 26131475 TI - Morphological analysis of the oribatid mite species Scutovertex pannonicus Schuster and description of its juvenile stages (Acari: Oribatida: Scutoverticidae). AB - This paper provides a detailed redescription of the adult as well as the first morphological description of all juvenile instars (inclusive egg, prelarva and earlier larval stages) of Scutovertex pannonicus. The adults are characterized by their relatively large size (692-892 MUm), their well developed sharply bordered foveae which are regularly distributed on the whole notogaster, except in the central field and the posterior notogastral brush-like setae ps1, h1,-h3. The exochorion of the eggs shows the typical structures for the genus Scutovertex like 'mushrooms' and granules with the species-specific expression of the 'mushrooms' and its substructures. The exochorion is covered with an extra thin layer which is typical for this species. The larva and the nymphs can be distinguished from those of S. sculptus and S. minutus mainly by their lateral setae l' and l" on tibia I which are strongly serrated and slightly broadened. PMID- 26131476 TI - Anopheles coluzzii and Anopheles amharicus, new members of the Anopheles gambiae complex. AB - Two new species within the Anopheles gambiae complex are here described and named. Based on molecular and bionomical evidence, the An. gambiae molecular "M form" is named Anopheles coluzzii Coetzee & Wilkerson sp. n., while the "S form" retains the nominotypical name Anopheles gambiae Giles. Anopheles quadriannulatus is retained for the southern African populations of this species, while the Ethiopian species is named Anopheles amharicus Hunt, Wilkerson & Coetzee sp. n., based on chromosomal, cross-mating and molecular evidence. PMID- 26131477 TI - Taxonomic revision of Leucascus Dendy, 1892 (Porifera: Calcarea) with revalidation of Ascoleucetta Dendy & Frederick, 1924 and description of three new species. AB - Sponges of the genus Leucascus are frequently recognised as possessing anastomosed tubes with choanocytes, and cortical and atrial membranes with pinacocytes. In the last years, five species of other genera were transferred to Leucascus, and several other species were suggested but not formally included in this genus. In the present work, all these species accepted or suggested as Leucascus were revised. According to our results, Leucascus is now composed of nine species: L. clavatus, L. leptoraphis comb. nov., L. lobatus, L. neocaledonicus, L. protogenes comb. nov., L. roseus, L. simplex (type species), L. albus sp. nov., and L.flavus sp. nov. The presence of spines in the apical actine of the tetractines had never been observed in Leucascus, but it was found in all species with tetractines in their skeletons. Some species were transferred from Leucascus to the genus Ascoleucetta, which is revalidated here based on important differences in the cortex. Modifications are also proposed in the definition of both genera. Based on our results, the family Leucascidae is now composed of Ascaltis, Leucascus and Ascoleucetta. PMID- 26131478 TI - Towards an Australian Bioregionalisation Atlas: A provisional area taxonomy of Australia's biogeographical regions. AB - The large number, definition, varied application and validity of named Australian biogeographical regions reflect their ad hoc development via disparate methods or case study idiosyncracies. They do not represent a coherent system. In order to resolve these uncertainties an Australian Bioregionalisation Atlas is proposed as a provisional hierarchical classification, accounting for all known named areas. This provisional area taxonomy includes a diagnosis, description, type locality and map for each named area within the Australian continent, as well as a first ever area synonymy. Akin to biological classifications, this Atlas seeks to provision universality, objectivity and stability, such that biogeographers, macroecologists and geographers, can test existing areas as well as proposing novel areas. With such a formalised and comparative system in place, practitioners can analyse the definition and relationships of biotic areas, and putatively minimise ad hoc explanations. PMID- 26131479 TI - Oxychilus (Drouetia) viridescens (Gastropoda: Pulmonata: Oxychilidae), a new species from Santa Maria, Acores, and a review of the subgenus. AB - Oxychilus (Drouetia) viridescens n.sp. is described from Santa Maria Island, Acores. It is conchologically similar to the sympatric Oxychilus (Drouetia) brincki Riedel, 1964, from which it is distinguished by the greenish coloration, the flatter spire and the slightly smaller number of whorls. Anatomically, the new species differs from all consubgenerics by the genital morphology: the penis is very thin, the distal half is wrapped in a very thick penial sheath; the epiphallus has two distinct portions, the proximal one attached to the edge of the penial sheath, the distal one attached to a constriction near mid-length of the penis; the atrial end of the vagina has a spongy, glandular appearance. A detailed morphological and anatomical comparison of the new species with the non umbilicated Oxychilus species of Santa Maria is presented. The species of Drouetia are reviewed and an identification key is provided. PMID- 26131480 TI - Phylogenetic placement of the European sand gobies in Gobionellidae and characterization of gobionellid lineages (Gobiiformes: Gobioidei). AB - The Mediterranean, northeastern Atlantic, and inland freshwaters of Europe and the Ponto-Caspian region host a distinct fauna of gobiiform fishes, including the sand gobies (Pomatoschistus Gill and related genera), all of which have been classified in the most diverse goby group, the family Gobiidae. Recent molecular phylogenetic analyses have suggested that the sand gobies are not gobiids, and are instead part of their sister clade Gobionellidae (Thacker and Roje 2011). Phylogenetic analysis of Pomatoschistus in the context of both gobiid and gobionellid taxa indicates that Pomatoschistus is part of Gobionellidae, specifically the Mugilogobius lineage. Gobionellidae includes 93 genera, which are arrayed into four lineages (Stenogobius, Mugilogobius, Periophthalmus and Northern Pacific). These lineages exhibit variation in characters of the jaw and suspensorium, including the shapes and relative positions of the palatine, quadrate, and ectopterygoid. The observations of the palatopterygoid complex in Gobionellidae of Harrison (1989) and Larson (2001) are supported and augmented. Gobionellidae generally exhibit suspensoria that are overall more elongated and gracile than those of gobiids: the palatine/ectopterygoid pair features a very short (Periophthalmus lineage) or elongate, pointed palatine (Mugilogobius, Northern Pacific, and Stenogobius lineages), with a relatively slender ectopterygoid and a short quadrate articulation. In Gobiidae, the palatine extends about halfway along the length of the ectopterygoid, and the ectopterygoid generally features a large, flat articulation with the quadrate. Suspensoria of Pomatoschistus and relatives are similar to those of other taxa in the Mugilogobius lineage. Placement of Pomatoschistus and relatives in Gobionellidae rather than Gobiidae is significant in that it indicates that sand gobies are not closely related to other European gobies, and has implications for any comparative evolutionary or biogeographic studies. PMID- 26131481 TI - Four new earthworm species and subspecies belonging to genus Amynthas and Metaphire (Oligochaeta: Megascolecidae) from Hainan Island, China. AB - Three new species and one new subspecies of earthworms from Hainan Island, China, are described: Amynthas dinganensis sp. nov., Amynthas tenuis sp. nov., Metaphire wuzhimontis sp. nov. and Metaphire magna minuscula subsp. nov. Amynthas dinganensis and Amynthas tenuis have two pairs of spermathecal pores in 5/6-6/7, and Metaphire wuzhimontis and Metaphire magna minuscula have two pairs of spermathecal pores in 7/8-8/9. COI and 16S gene fragments of the new species taxa have been sequenced. We provide comparisons between these new species taxa and related species using morphological and molecular characters. PMID- 26131482 TI - Two new species of Ovitamon Ng & Takeda, 1992 (Crustacea: Brachyura: Potamidae) from the Philippines. AB - Two new species of potamid freshwater crabs of the genus Ovitamon Ng & Takeda, 1992, are described from the islands of Mindoro and Panay, Philippines. The two new species can easily be distinguished from congeners by the morphologies of their carapaces and male first gonopods. Six species of Ovitamon are now known from the islands of central and western Philippines. PMID- 26131483 TI - Development sites and early stages of eleven species of Clusiidae (Diptera) occurring in Europe. AB - Two hundred and ninety-six rearing records of 11 clusiid species (Diptera, Clusiidae) were obtained from 8 tree species in England, Finland, France, Norway, Russia and Scotland, mainly during the period 1994 to 2004. Larvae and puparia were found between annual layers of whitewood (sapwood and heartwood) of wet, decay-softened, dead wood. Levels of host tree specificity were low, most species were reared from 2-4 host trees, maximum 6. The clusiid larva is distinguished by: a small, translucent head skeleton with an obliquely-shaped apex to the artium; a pseudocephalon fixed in an inverted position except for an external, flattened section bearing the antennomaxillary organs; a spherical prothorax with a truncate rim embedded with sensilla and, a wedge-shaped anal segment bearing a pair of conspicuous, sclerotised, red-brown hooks on the inner margins of which are the posterior spiracular plates. Many of these features support a distinctive feeding mechanism, spot-sucking of biofilm coating wet, decaying whitewood. Early stage characters support the results of recent supraspecific taxonomic and systematic investigations, such as the synonymy of Paraclusia Czerny under Clusia Haliday and the recognition of species groups in Clusiodes Coquillett. Based on early stages, supraspecific clusiid taxa are easily recognised but at species level, differences are relatively fine-grained and minor. A key is provided to identify puparia of species reared in this study. PMID- 26131484 TI - Liolaemus carlosgarini and Liolaemus riodamas (Squamata: Liolaemidae), two new species of lizards lacking precloacal pores, from Andean areas of central Chile. AB - Most of the lizards of the Liolaemus genus present precloacal pores in males, with few exceptions in species of the lineomaculatus and neuquensis groups, and in the elongatus-kriegi complex. The elongatus-kriegi complex, belonging to the Liolaemus (sensu stricto) subgenus, is composed of medium sized, saxicolous, viviparous and insectivorous or omnivorous lizards, distributed between the Andean and Patagonian zones of Chile and Argentina. We reviewed the taxonomic history of this group, and we describe two new species, Liolaemus carlosgarini, found in the vicinity of the Maule Lagoon, in the Maule Region, Chile, and Liolaemus riodamas, described from the population that was originally designated as Liolaemus cf ceii, from Las Damas River, near the Termas del Flaco locality, in the Libertador Bernardo O'Higgins Region, thereby based on this research L. ceii is eliminated from the species belonging to Chile. Both species have as a diagnostic character the absence of precloacal pores, and we suggest here their presumptive systematic relationships in Liolaemus. We analyzed ten species of Liolaemus, in order to perform a phylogenetic analysis based on external morphology, using mostly squamation and morphometric characters. The analysis was performed using PAUP, with the Maximum Parsimony criterion. In addition, through diaphanisation, we studied and described the osteology of the new species. We conclude that species lacking precloacal pores do not form a monophyletic group, and that constructing a phylogeny using only external morphology, at least for this group of reptiles, is insufficient to establish solid phyletic relationships. Other sort of characters should complement the morphological ones. PMID- 26131485 TI - A contribution to the systematics of Neotropical Tanytarsus van der Wulp: first descriptions from Ecuador (Diptera: Chironomidae: Tanytarsini). AB - First specific records of Tanytarsus van der Wulp from the Ecuadorian mainland based on detailed descriptions are presented. Tanytarsus cayambe sp. nov. shows an interesting set of characters known from several Neotropical Tanytarsus as well as from species of the recurvatus group of the northern distribution. Tanytarsus cotopaxi sp. nov. is placed in the riopreto species group; as a result an emended diagnosis for adult males of the group is proposed. The diagnostic description of Tanytarsus curvicristatus Contreras-Lichtenberg is also complemented. PMID- 26131486 TI - A new species of the Callophrys mystaphia Miller, 1913--group from Iran (Lepidoptera: Lycaenidae: Eumaeini). AB - A new species, recently misinterpreted as Callophrys mystaphia Miller, 1913, Callophrys mystaphioides Krupitsky & Kolesnichenko sp. n., is described from Central Iran (Esfahan Province). The new species differs from C. mystaphia in the combination of external characters and morphology of genitalia. Possible relations of C. mystaphia--species group with other Palaearctic Callophrys are discussed. PMID- 26131487 TI - Scale surface microstructure and scale size in the tooth-carp genus Aphanius (Teleostei, Cyprinodontidae) from endorheic basins in Southwest Iran. AB - A substantial number of species within the tooth-carp Aphanius Nardo, 1827 (Cyprinodontidae, Teleostei) has been recorded from the endorheic drainage systems of Iran, and several isolated populations in these systems may deserve species status. Descriptions of these species and populations have been based mainly on morphological and molecular data; however, the characters related to the fish scales have not up to now been intensively studied and employed for the identification of the species belonging to this genus. The objective of this study is to test as to whether (i) scale surface morphology, (ii) scale surface microstructure, and (iii) scale size can be used to discriminate species and/or populations and, (iv) to discuss the possible causes of the observed differences. To achieve these objectives, scales of three species of the genus Aphanius from endorheic basins in SW Iran, viz. A. sophiae (nine populations from the Kor River Basin), A. farsicus (four populations from the Maharlu Lake Basin) and A. pluristriatus (a single population from the Mond River Basin) have been studied using SEM images, scale measurements, and uni- and multivariate statistics. It is opined that scale surface morphology and microstructure cannot help in distinguishing the species, but can be employed to discriminate certain populations of A. sophiae (those from Safashahr, Kharameh, Tashk, Gol). In addition, scale size and J-indices, respectively, represent a valuable tool for species separation, which corroborates earlier studies for the use of these indices in taxonomy. Major driving forces of the differentiation within A. sophiae probably include habitat fragmentation resulting from the geological history and local adaptations. Thus the differentiation results from a balance between both genetic and environmental effects. PMID- 26131488 TI - The first palpimanid spiders from Bolivia: two new species of the genus Otiothops MacLeay, and the female of Fernandezina pulchra Biraben (Araneae: Palpimanidae: Otiothopinae). AB - The araneomorph spider family Palpimanidae is reported from Bolivia for the first time. Two new species: Otiothops kathiae and O. naokii are described and illustrated based on specimens recently collected in Santa Cruz Department. Additionally, Fernandezina pulchra Biraben, 1951 previously known only from Formosa, in northern Argentina, is newly recorded from Santa Cruz, and the female is described for the first time. Potential relationships with previously described species are also briefly discussed. PMID- 26131489 TI - New Guinea Onthophagus: taxonomy of ten small, unicolored new species (Coleoptera: Scarabaeidae: Scarabaeinae). AB - The taxonomy of small, unicolor brown to black Papuasian species of the genus Onthophagus Latreille, 1802 is discussed. Two multi-species groups are defined in the nominotypical subgenus Onthophagus, one with broad and one with narrow dorsal eye foramina (O. acerus and O. kokodentatus groups, respectively). Twelve species are listed, keyed, and diagnosed. Ten of these are new species from Papua New Guinea (PNG) and West New Guinea (WNG, Indonesia), here described in the Onthophagus acerus group: O. aceroides (WNG), O. baiyericus (PNG), O. bituberoculus (WNG), O. daymanus (PNG), O. kokocellosus (PNG), O. kokopygus (PNG); in the Onthophagus kokodentatus group: O. dissidentatus (PNG), O. kokodentatus (PNG), O. kukali (PNG); and an ungrouped new species: Onthophagus ofianus (PNG). Two previously named species, O. acer Gillet, 1930 and O. mimikanus Balthasar, 1969, are briefly diagnosed and discussed. PMID- 26131490 TI - The Oriental genus Nasimyia (Diptera: Stratiomyidae): Geographical distribution, key to species and descriptions of three new species. AB - In this paper, three new species of Nasimyia Yang & Yang, 2010, N. eurytarsa sp. nov., N. rozkosnyi sp. nov. and N. elongoverpa sp. nov. from the Oriental region are described and illustrated; N. nigripennis Yang & Yang, 2010 is found to be a junior synonym of N. megacephala Yang & Yang, 2010 (syn. nov.). Chelonomima signata de Meijere 1924 is combined as Pseudomeristomerinx signata (de Meijere, 1924) comb. nov.. Keys to the Oriental genera of Pachygasterinae with elongate abdomens and the species of Nasimyia are provided, as well as distribution maps of the four species of Nasimyia. PMID- 26131491 TI - Review of Otites Latreille (Diptera: Ulidiidae) from Israel with two new species and notes on biology and behavior. AB - The genus Otites Latreille was recorded for the first time from Israel during the study of Ulidiidae in the local fauna in 2009-2012, with three species occurring here: O. grata Loew, O. nox n. sp. and O. vitalyi n. sp. The three species are described and illustrated, and a key for their identification is provided. Laboratory behavioral observations on live O. grata individuals revealed a new mating trophallaxis behavior: a transfer of substance, during copulation, through the genital tracts of the male to the female, which the female expels and consumes after copulation. PMID- 26131492 TI - Kempnyia Puri, a new species of Perlidae (Plecoptera) from Rio de Janeiro, Brazil. AB - Kempnyia puri sp. nov. is described from male specimens from Rio de Janeiro State, southeastern Brazil. This species is distinguished from its congeners by the male genitalia bearing moderately long and curved hooks with apex directed laterad and a large and rounded dorsal projection of the penial ring. PMID- 26131493 TI - Review of the bamboo-feeding species of genus Scaphoideus (Hemiptera: Cicadellidae: Deltocephalinae) from China, with description of one new species. AB - The bamboo-feeding species of genus Scaphoideus Uhler (Hemiptera: Cicadellidae: Deltocephalinae) from China are reviewed to include 7 species: S. conicaplateus Li & Dai, 2004 (China: Guizhou), S. fanjingensis Li & Dai, 2004 (China: Guizhou), S. festivus Matsumura, 1902 (China: Guizhou, Yunnan, Sichuan, Shaanxi, Ningxia, Hunan, Beijing, Hebei, Henan, Jiangxi, Fujian, Guangdong, Guangxi, Hainan and Taiwan; India; Sri Lanka; Japan; Korea), S. kumamotonis Matsumura, 1914 (China: Guizhou, Yunnan, Tibet, Sichuan, Zhejiang and Henan; Japan), S. nigrigenatus Li, 1990 (China: Guizhou, Sichuan and Hubei), S. nigrivalveus Li & Wang, 2005 (China: Guizhou and Hubei) and S. yaanensis sp. nov. (China: Sichuan). All seven species are re-illustrated and photographed. The new species is described. A key to the bamboo-feeding species of Scaphoideus is also provided. PMID- 26131494 TI - Larval morphology of Lebertia longiseta Bader, 1955, L. dubia Thor, 1899 and Oxus nodigerus Koenike, 1898 (Acari, Hydrachnidia: Lebertiidae, Oxidae). AB - Illustrated descriptions of the larvae of the water mite species of Lebertia longiseta Bader, 1955, Oxus nodigerus Koenike, 1898 and redescription of the larva L. dubia (Thor, 1899) are presented. PMID- 26131495 TI - Sirovena Boucek (Pteromalidae: Pireninae), a new member of the fig wasp community associated with Ficus microcarpa (Moraceae). AB - Sirovena Boucek (Chalcidoidea: Pteromalidae, Pireninae) was known only from females of its type species, S. stigma Boucek, 1988. Males and host associations were both unknown. Both sexes of a second species of Sirovena, S. costallifera sp. nov., reared from Ficus microcarpa L. (Moraceae) in Yunnan, China, are described based on morphological characters and mitochondrial COI sequences. The males of S. costallifera show sexual dimorphism in body coloration, structure of the antennae and notauli, and body sculpture. Reliable host records of Pireninae are Cecidomyiidae (Diptera). Because midges also parasitize some figs, we speculate that S. costallifera is a parasitoid of some cecidomyiid midge that attacks fig syconia. A key to differentiate the two species is provided. PMID- 26131496 TI - The larva of the genus Palaeosynthemis Forster, 1903 (Odonata: Anisoptera: Synthemistidae) and a generic key to the larvae of non-New Caledonian Synthemistidae. AB - The larva of Palaeosynthemis Forster, 1903, based on P. cyrene (Lieftinck, 1953), is described and illustrated for the first time. A diagnosis of the genus is given. A larval generic key to all known non-New Caledonian genera of Synthemistidae is provided. PMID- 26131497 TI - Notes on the Paleophilotes (Inderskia) panope (Eversmann, 1851) (Lepidoptera: Lycaenidae), a rare and little known lycaenid taxon for Europe. PMID- 26131498 TI - New Zealand Bodotriidae (Crustacea: Cumacea). AB - The cumacean fauna of New Zealand has been little studied, and recent collections on the Chatham Rise and Challenger Plateau have yielded many new species and new genera of Cumacea. A recent manuscript on the New Zealand Nannastacidae (Gerken 2012) increased the described New Zealand fauna by 66%. Within the Bodotriidae, 6 new species were discovered. The new species Apocuma chathamensis n. sp., A. sculpta n. sp., Bathycuma dayae n. sp., Cyclaspis petrescui n. sp., C. hayeae n. sp. and C. zealandiaensis n. sp. are described, and keys to all New Zealand Bodotriidae are provided. PMID- 26131499 TI - Revision of subgenera of Stenichnus Thomson, with review of Australo-Pacific species (Coleoptera, Staphylinidae, Scydmaeninae). AB - Subgenera of the speciose ant-like stone beetle genus Stenichnus Thomson are revised. The genus is re-classified and only two subgenera are retained: Stenichnus s. str. and Scydmaenichnus Reitter. Two remaining subgenera, Austrostenichnus Franz and Scydmaenilla King, are elevated to the genus rank (the status of Scydmaenilla, originally described as a genus and later reduced to a subgenus of Stenichnus, is restored). Two species occurring in New Zealand, Stenichnus insignis (Broun) and Stenichnus kuschelianus Franz, previously classified in Stenichnus (Austrostenichnus), are placed in a separate genus Zeanichnus gen. nov. (with Scydmaenus insignis Broun as a type species). Scydmaenilla is divided into two subgenera: Scydmaenilla s. str. and Scydmaenillunia subg. nov. (with Scydmaenilla adelaidensis Franz as a type species). Lectotypes are designated for Stenichnus (Scydmaenichnus) fossifrons Reitter, Scydmaenilla pusilla King and Scydmaenilla constricta Lea. All Australo Pacific species, previously placed in Stenichnus, are redescribed: Austrostenichnus caledonicus Franz (New Caledonia), Zeanichnus insignis (Broun) comb. nov. (New Zealand), Zeanichnus kuschelianus (Franz) comb. nov. (New Zealand), Scydmaenilla (s. str.) pusilla King, stat. rest. (Australia), S. (s. str.) constricta Lea, stat. rest. (Tasmania), S. (s. str.) queenslandica Franz (Australia), S. (s. str.) thompsoniana Franz (Australia), S. (s. str.) brisbanensis Franz (Australia), S. (s. str.) sydneyana Franz (Australia), and S. (Scydmaenillunia) adelaidensis Franz (Australia). A possible synonymy of Scydmaenilla queenslandica and S. thompsoniana is discussed, not possible to verify on the basis of the available material. PMID- 26131500 TI - Bitentaculate Cirratulidae (Annelida: Polychaeta) from the northwestern Pacific Islands with description of nine new species. AB - Thirteen cirratulid species from the Hawaiian, Mariana and Marshall Islands are described. Nine species are new to science: Aphelochaeta arizonae sp. nov., Aphelochaeta honouliuli sp. nov., Caulleriella cordiformia sp. nov., Chaetozone michellae sp. nov., Chaetozone ronaldi sp. nov., Monticellina anterobranchiata sp. nov., Monticellina hanaumaensis sp. nov., and Tharyx tumulosa sp. nov., from Oahu, Hawaii and Aphelochaeta saipanensis sp. nov., from Saipan in the Mariana Islands. Dodecaceria fewkesi and Monticellina nr. cryptica are newly recorded from the Hawaiian Islands. Dodecaceria laddi is widely distributed in the western Pacific and material collected from the Hawaiian, Mariana and Marshall islands is described. We provide SEM photographs for all species in addition to line drawings and methyl green staining pattern photographs for the new species. PMID- 26131501 TI - Taxonomic study of the genus Kapsa Dworakowska with a new subgenus, and new combinations and records for Tautoneura Anufriev (Hemiptera: Cicadellidae: Typhlocybinae: Erythroneurini). AB - The genus Kapsa Dworakowska is redescribed and a new subgenus Kapsa (Rigida) Cao & Zhang is established to include thirteen species, a key to males of the subgenus is provided, and eight new species from China are described and illustrated: Kapsa aculeiformis, K. apicispina, K. brevis, K. explanata, K. furcata, K. imminuta, K. mnegaprocessa and K. serrata spp. nov.. Based on detailed study of previously described species, Kapsa yanheensis Song & Li, 2012 is considered a synonym of Tautoneura albida (Dworakowska, 1970). Four species previously placed in Kapsa are transferred to Tautoneura Anufriev: Tautoneura decorata (Dworakowska, 1981), T. diasonica (Chiang & Knight, 1990), T. elscinta (Chiang & Knight, 1990) and T. puerensis (Song & Li, 2012). K. alba Dworakowska, 1981 and T. ahmedi Dworakowska, 1977 are reported for the first time from China. PMID- 26131502 TI - Three new species of Glossobalanus (Hemichordata: Enteropneusta: Ptychoderidae) from western North America. AB - Twenty three enteropneust species have been described from the west coast of North America, including one species from the family Ptychoderidae; Glossobalanus berkeleyi from the Salish Sea, Vancouver Island. Here we use morphology to describe three additional species of acorn worms in the genus Glossobalanus: G. williami from Cape Arago, Oregon; G hartmanae and G. barnharti from La Jolla, California. Notes on the habit and localization of each species as well as a dichotomous key to the genera of the family Ptychoderidae are provided. PMID- 26131503 TI - Callogobius winterbottomi, a new species of goby (Teleostei: Gobiidae) from the Western Indian Ocean. AB - Callogobius winterbottomi new species is described from the 33.8 mm SL holotype and two paratypes (32.2 mm SL and 22.9 mm SL) from the Comoros, Western Indian Ocean. It is distinguished from all other known Callogobius species by the following combination of characters: sensory pores absent, 23-26 scales in lateral series, and sensory papillae preopercular row not continuous with transverse opercular row. One additional specimen of Callogobius winterbottomi was located from South Africa. A new standardized naming system for Callogobius sensory papillae rows is presented for identification and clarification of character states among Callogobius species. The new species is tentatively placed among what we term the "sclateri group", a clade including C. sclateri (Steindachner) and three other species that exhibit a modified female urogenital papilla with lateral distal flaps and elongate ctenii on the caudal peduncle scales. Callogobius tutuilae (Jordan & Seale) is removed from synonymy with C. sclateri because it has partially united pelvic fins (vs separate) and the preopercular sensory papillae row is continuous with the transverse opercular row (vs separate). PMID- 26131505 TI - A new species of Platygaster Latreille (Hymenoptera: Platygastridae) parasitizing Chilophaga virgati Gagne (Diptera: Cecidomyiidae). AB - Platygaster chilophagae, new species, is described from specimens reared from larvae of Chilophaga virgati Gagne collected and reared in eastern South Dakota. The host larva feeds on the basal meristematic tissues of the inflorescence of Panicum virgatum L. This new species seems to lack immediate affinities with any described Platygaster species in its combination of characteristics, and is compared to and discriminated from six other species. Polyembryony is suggested by the presence of cocoon clusters containing 4-14 pupae from each host larva. PMID- 26131504 TI - Systematics of Sturnira (Chiroptera: Phyllostomidae) in Ecuador, with comments on species boundaries. AB - Molecular and morphological analyses of variation often conflict with historical species descriptions based on a few characters and small samples sizes. Here we present a molecular phylogeny together with a quantitative morphologica analysis of the species in Sturnira in Ecuador. The 438 terminal taxa or organisms included in the anlaysis occur within a total of 10 ingroup lineages, which contain considerable substructure. Some species, as recognized by their morphologica traits, form paraphyletic arrangements with other taxa. We could not distinguish the close species pairs S. erythromos/S. bogotensis and S. ludovici/S. oporophilum in morphospace and therefore when distinct lineages were recovered genetically, they initially contained mixed membership of specimens identified using morphological criteria. Similarly the qualitative character states that diagnose S. luisi in its original description are not recovered in a quantitative analysis of morphological variation and thus S. luisi cannot be mapped to a single lineage in a molecular phylogeny. We presen additional evidence to corroborate the existence of S. perla as a species. We found a remarkable geographic structure within some species containing sister pairings, with lineages having a clear eastern or western distribution in relation to the Andes. Our analysis demonstrates the potential for conflict between character based diagnoses, analysis of morphological variation and molecular phylogenetics in the identification of species and supports a combined approach to this problem. PMID- 26131506 TI - A new species of Nemipterus (Pisces: Nemipteridae) from the Western Indian Ocean. AB - A new species of threadfin bream, Nemipterus flavomandibularis, from the Western Indian Ocean is described and figured. The new species appears most closely related to N. bipunctatus (Valenciennes), but differs principally in colour pattern: N. flavomandibularis is distinct from N. bipunctatus in having two yellow bands on the snout, the upper lip narrowly edged with yellow; and lower lip and chin beneath lip yellow, this colour extending as a narrow band posteriorly to lower margin of opercle. Also, in N. flavomandibularus the scale rows below the lateral line are more or less horizontal (versus distinctly ascending anteriorly in N. bipunctatus), and the maxillary reaches to between level of posterior nostril and anterior margin of eye (versus reaching to below the anterior half of the eye in N. bipunctatus). PMID- 26131507 TI - The World's largest known Gorgonian. AB - Gorgonians in the deep sea can be much larger than their shallow water counterparts, but there are only a few scattered measurements. We have estimated the size of a chrysogorgiid gorgonian, Iridogorgia magnispiralis Watling 2007, observed from a submersible on Twin Banks in the Northwest Hawaiian Islands, as being 5.7 m tall. PMID- 26131508 TI - Notes on Bonea Roewer, 1914 and Lomanius Roewer, 1923 (Opiliones: Laniatores: Podoctidae), with the description of three new species from China. AB - The harvestman genus Bonea Roewer, 1914 and its type species B. sarasinoruni Roewer, 1914 are redescribed based on the type material. In addition, two new species of Bonea from Hainan Island, China, are described and illustrated: B. zhui sp. nov. and B. tridigitata sp. nov. A new species of Lonianius Roewer, 1923 from Yunnan Province, China, is also described and illustrated: L. bulbosus sp. nov.. Keys to the 10 species of Bonea and the six species of Lomanius are provided. Paralomanius Goodnight & Goodnight, 1948 is revalidated from the synonymy of Lomanius, carrying as junior synonym Eulomanius Roewer, 1949, and containing two species from Micronesia (Paralomanius longipalpus Goodnight & Goodnight, 1948) and Philippines (Paralomanius mindanaoensis (Suzuki, 1977) new status). Bonea is transferred from the Ibaloniinae to Podoctinae. These are the first records of named species of Podoctidae from China. PMID- 26131509 TI - Ribautia lewisi sp. nov., a new centipede from Argentina with unusual tentorial process (Chilopoda: Geophilomorpha, Geophilidae). AB - Ribautia lewisi sp. nov. (Chilopoda: Geophilomorpha, Geophilidae) is herein described and illustrated after the holotype (male), paratypes (males and females), and additional non type specimens from Northeastern Argentina (Mesopotamian region). The new species is characterized by having a cluster of coxal organs in each coxopleuron of the ultimate leg-bearing segment and a claw like pretarsus in the ultimate legs, bearing a very unusual feature, in that the internal limbs of tentorium have a conspicuous tooth-shaped sclerotized process directed inward. R. lewisi sp. nov. is only the second confirmed record of the genus Ribautia from Argentina, the other being R. jakulicai Pereira, 2007 from Northwestern region of the country (Yungas biogeographical province). PMID- 26131510 TI - Bathyconchoeciinae, a new subfamily of deep oceanic planktonic halocyprid Ostracod (Myodocopa, Ostracoda). AB - Species of the genera Bathyconchoecia and Scottoecia are currently classified in the subfamily Euconchoeciinae together with species of the genus Euconchoecia. The morphological and ecological characteristics of many of the species currently attributable to these two taxa are compared with a range of Euconchoecia species and are shown to differ extensively. These differences are sufficient to separate these taxa at the subfamily level. Therefore, a new subfamily, the Bathyconchoeciinae is proposed to accommodate all the species currently classified in the genera Bathyconchoecia and Scottoecia. PMID- 26131511 TI - Leaf litter copepods from a cloud forest mountain top in Honduras (Copepoda: Cyclopidae, Canthocamptidae). AB - Five different species of Copepoda were extracted from a leaf litter sample collected on the top (at 2000 m a.s.l.) of a cloud forested mountain in El Cusuco National Park, Honduras. Three of them, one Cyclopidae and two Canthocamptidae are new to science, and are described herein. Olmeccyclops hondo sp. nov. is the second representative thus far known of this New World genus. Moraria catracha sp. nov. and Moraria cusuca sp. nov. are the first formally described members of the genus occurring in Central America. The concept of a "Moraria-group" is considered to be an artificial grouping and is limited here to the genera Moraria and Morariopsis only. The distributional range of this group is essentially Holarctic, with the mountainous regions in Honduras, and probably in west Nicaragua, as the southernmost limits in the New World. PMID- 26131512 TI - The taxonomy of the Japanese oak red scale insect, Kuwania quercus (Kuwana) (Hemiptera: Coccoidea: Kuwaniidae), with a generic diagnosis, a key to species and description of a new species from California. AB - The oak red scale insect, Kuwania quercus (Kuwana), was described from specimens collected from the bark of oak trees (Quercus species) in Japan. More recently, the species has been identified from California and China, but Californian specimens differ morphologically from Japanese material and are considered here to be a new species based on both morphological and molecular data. In this paper, an illustrated redescription of K. quercus is provided based on type specimens consisting of adult females, first-instar nymphs and intermediate-stage females, and a lectotype is designated for Sasakia quercus Kuwana. The new Californian species, Kuwania raygilli Wu & Gullan, is described and illustrated based on the adult female, first-instar nymph and intermediate-stage female. A new generic diagnosis for Kuwania Cockerell based on adult females and first instar nymphs, and a key to species based on adult females are included. PMID- 26131513 TI - After eighty years of misidentification, a name for the glass catfish (Teleostei: Siluridae). AB - We resolve the identity of the glass catfish, a species of Asian freshwater fish commonly encountered as an ornamental fish and an experimental subject that has long been misidentified as either Kryptopterus bicirrhis or K. minor. Our study indicates that the glass catfish is an unnamed species distinct from either, which we describe here as Kryptopterus vitreolus. Kryptopterus vitreolus is known from river drainages in peninsular and southeastern Thailand, and is distinguished from congeners in having a combination of: transparent body in life, maxillary barbels reaching beyond the base of the first anal-fin, dorsal profile with a pronounced nuchal concavity, snout length 29-35% head length (HL), eye diameter 28-34% HL, slender body (depth at anus 16-20% standard length (SL)) and caudal peduncle (depth 4-7% SL), 14-18 rakers on the first gill arch, and 48 55 anal-fin rays. PMID- 26131514 TI - Resolving an enigma by integrative taxonomy: Madagascarophis fuchsi (Serpentes: Lamprophiidae), a new opisthoglyphous and microendemic snake from northern Madagascar. AB - Herpetological surveys in the dry forests of the limestone massif Montagne des Francais in the far north of Madagascar have recently yielded a number of undescribed reptile species. Here we describe an additional new and potentially microendemic species of the snake genus Madagascarophis (Squamata: Serpentes: Pseudoxyrhophiinae) which lives in this massif syntopically with M. colubrinus septentrionalis and differs distinctly from M. colubrinus and M. meridionalis in its mitochondrial and nuclear DNA sequences. Morphologically Madagascarophis fuchsi sp. nov. is characterized by a broad contact between the posterior inframaxillaries (genials), 25 dorsal scale rows at midbody, and a low number of ventrals (171-172). We redescribe the holotype of M. ocellatus and present new data on the morphological variation of the northern subspecies M. c. septentrionalis and M. c. citrinus. Although Montagne des Francais has recently been included into the network of nature reserves in Madagascar, continuous deforestation is strongly threatening this important center of reptile endemism. In line with the assessment of other microendemic reptiles of this massif we suggest to consider the new species as Critically Endangered according to the IUCN criteria and encourage new efforts to protect this area more efficiently. PMID- 26131515 TI - Phylogenetics of the tribe Phalacropsyllini (Siphonaptera: Ctenophthalmidae: Neopsyllinae) based on molecular and morphological evidence. AB - Six genera of the tribe Phalacropsyllini were analysed based on molecular (18S rDNA and 28S rDNA) and morphological characters, using maximum parsimony analyses and Bayesian inference. The results support the paraphyly of the tribe Phalacropsyllini, as shown in a previous study based only on molecular characters. Three main clades were identified: one includes the genera Neopsylla, Epitedia, Catallagia, and Delotelis; another includes Phalacropsylla and Strepsylla; and a third one includes only Meringis. In order to propose a phylogenetic classification we recognize three tribes, transferring Epitedia, Catallagia and Delotelis to Neopsyllini; keeping Phalacropsyllini only for Phalacropsylla and Strepsylla; and proposing the new tribe Meringini for Meringis. PMID- 26131516 TI - A new genus of Eucharitidae (Hymenoptera: Chalcidoidea), with notes on life history and immature stages. AB - Neolirata new genus (Eucharitidae: Eucharitini) is recognized based on males and females, with new descriptions of eggs, planidia and pupae. Redescriptions are provided for N. alta (Walker) and N. daguerrei (Gemignani) (comb. nov. transferred from Lirata) and a new description of N. furcula sp. nov. is presented. Females of N. alta deposit their eggs on the underside of leaves of Pseudabutilon virgatum (Cav.) Fryxell (Malvaceae) and N. daguerrei on the underside of Urvillea chacoensis Hunz (Sapindaceae). A key to species is included. PMID- 26131518 TI - Jubogaster towai, a new Neotropical genus and species of Trogastrini (Coleoptera: Staphylinidae: Pselaphinae) exhibiting myrmecophily and extreme body enlargement. AB - Jubogaster towai gen. et sp. nov. is described from a colony of Pheidole xanthogaster Wilson (Hymenoptera: Formicidae) in the Peruvian Amazon. The new taxon is amongst the largest pselaphine species known. Its transverse head implies an affinity with Trogastrini (Pselaphinae: Euplectitae), but J. towai lacks typical characters diagnostic for trogastrines and possesses others, such as a Jubini-like pronotum and equally-sized tarsal claws, that obscure its systematic relationships. To place J. towai phylogenetically, we sequenced a fragment of 28s rDNA for the new species and a range of other pselaphines, including members of Trogastrini and other tribes of Euplectitae. The topology produced by this analysis supports the inclusion of Jubogaster in Trogastrini, thereby indicating that morphology within this tribe can be more malleable than previously thought. Many of the largest pselaphine taxa are guests of social insect colonies. We discuss whether an evolutionary correlation (or causal relationship) exists between body enlargement and an inquilinous lifestyle in Pselaphinae. PMID- 26131517 TI - A new tardigrade Doryphoribius maasaimarensis sp. nov. (Eutardigrada: Hypsibiidae) from Kenya. AB - A new tardigrade, Doryphoribius maasaimarensis sp. nov., is described from a moss sample collected in Masai Mara Game Reserve, Kenya. The new species is characterized by having a reticulate dorsal cuticle with small tubercles; nine transverse rows of dorsal gibbosities (configuration IX:4-6-4-6-4-6-4-4-2); pharyngeal bulb with two macroplacoids and no microplacoid; claws with short and thin accessory points; small, smooth lunules under the claws. The new species is most similar to Doryphoribius zyxiglobus (Horning, Schuster & Grigarick, 1978). Both exhibit two macroplacoids, similar cuticular pattern and the same configuration of gibbosities. However, in Doryphoribius maasaimarensis sp. nov. the cuticular tubercles are less close, buccal tube slightly longer with respect to the body length, more gradual curvature of the buccal tube, different claws shape and thinner accessory points. PMID- 26131519 TI - Description and ecology of a new species of Eriopeltastes Burmeister & Schaum, 1840 (Coleoptera: Scarabaeidae: Cetoniinae: Trichiini), from KwaZulu-Natal, South Africa. PMID- 26131520 TI - Description of Quercorhabditis rajouriensis gen. n., sp. n. (Nematoda: Rhabditidae). AB - Quercorhabditis rajouriensis gen. n., sp. n. is described and illustrated. Distinctive characters include a labial region set off by a constriction and wider than adjoining body, heavily sclerotized cheilostom with arched rhabdions, barely differentiable stegostom, amphidelphic gonads, spicules with a free dorsal arm, and a leptoderan bursa with ten pairs of bursal papillae. The new genus resembles Diploscapteriodes Rahm, 1928 in the shape of cheilostom, presence of amphidelphic gonads, leptoderan bursa and long conoid tail. However, it can be differentiated from the latter genus in the shape of labial region, cheilostomal sclerotization, absence of ridge-like tooth in gymnostom, having spicules with a free dorsal arm, somewhat boat-shaped gubernaculum and in having ten pairs of bursal papillae. The new genus also resembles Curviditis (Dougherty, 1953) Andrassy, 1983, Rhabditella (Cobb, 1929) Chitwood, 1933 and Metarhabditis Tahseen et. al., 2004 in having spicules with free dorsal arm. However, it can be differentiated from these related genera by its heavily cuticularised cheilostom with arched rhabdions and barely differentiable stegostom. The new genus can further be differentiated from Curviditis and Rhabditella in having a well developed bursa and from Metarhabditis by its leptoderan bursa with ten pairs of bursal papillae arranged in 3+4+3 arrangement. PMID- 26131521 TI - Two new species and one newly recorded species of the genus Kamaka (Crustacea: Amphipoda) from the Hainan Province, South China Sea. AB - A total of 5 species of the genus Kamaka (Crustacea: Amphipoda) are identified from Hainan Province, South China Sea. In those, one species, Kamaka excavata Ariyama, 2007, is recorded for the first time in Chinese waters. Two new species, Kamaka corophina sp. n. and Kamaka foliacea sp. n., are described. A key to the Chinese species is provided. They were collected from littoral zone, mud flat in seaweed of mangrove side, brackish water and seawater, sifted out with sieve. PMID- 26131522 TI - Replacement for a preoccupied Docosia Winnertz (Diptera: Mycetophilidae) name. PMID- 26131523 TI - Studies on the genus Aporcelaimellus Heyns, 1965 (Nematoda, Dorylaimida, Aporcelaimidae). Four atypical species with simple uterus from Southern Iberian Peninsula. AB - Three new and one known species of the genus Aporcelaimellus, collected mainly in natural areas from the Iberian Peninsula and characterized by having a simple uterus and atypical caudal region are described and illustrated, including line drawings, LM pictures and/or SEM pictures. Aporcelaimellus deserticola sp. n. is distinguished by its body 1.79-2.43 mm long, lip region 14-16 pm broad and offset by expansion rather than by constriction, odontostyle 18-21 um long, neck 464-555 um long, pharyngeal expansion 234-283 um long or 49-52% of total neck length, a dorsal cell mass present at level of anterior end of intestine, uterus 34-67 um long or 0.6-1.1 times the corresponding body diameter, V= 49-55, tail conical with rounded terminus (29-43 um, c = 47-66, c' = 0.9-1.4) and bearing a short but perceptible hyaline portion, and male unknown. Aporcelaimellus hyalinus sp. n. is characterized by its body 1.49-2.23 mm long, lip region offset by constriction and 13-16 um broad, odontostyle 14-16 um long, neck 389-474 um long, pharyngeal expansion 183-242 um long or 45-53% of total neck length, uterus 44-106 um long or 0.7-1.8 times the corresponding body diameter, V = 48-55, tail conical with rounded terminus (27-41 um, c = 38-68, c' = 1.0-1.4) and short inner core, spicules 56 um long, and seven irregularly spaced ventromedian supplements. Aporcelaimellus rarus sp. n. is distinguished by its body 1.96-2.34 mm long, lip region offset by constriction and 14-16 um broad, odontostyle 15-16 um long, neck 411-518 um long, pharyngeal expansion 196-270 um long or 48-52% of total neck length, a dorsal cellular mass at a short distance behind the cardia, uterus 63 96 um long or 0.8-1.5 times the corresponding body diameter, V= 51-56, female tail short and conical (28-40 um, c = 50-74, c' = 0.7-0.9) with rounded terminus and bearing a dorsal concavity at its posterior half, and males unknown. New data are provided for A. salicinus. A discussion of these atypical species is also provided. PMID- 26131524 TI - The ANDEEP Tanaidacea (Crustacea: Peracarida) revisited I: the family Agathotanaidae Lang, with description of four new species. AB - Specimens collected during the ANDEEP I and II expeditions revealed a number of new species of tanaidacean from the family Agathotanaidae. One new species of Metagathotanais (M. furcilla), two of Paragathotanais (P. diunguisus, P. triunguisus) and one of Paranarthrura, (P. coimbrai) are described in this study. Metagathotanais furcilla can be separated from all other species by the incomplete fusion of the pleonites and the presence of dorsodistal spines of the propodi of pereopods 4-6. Paragathotanais diunguisus can be separated from all other species by the pereopod propodi with numerous distal spines and the numbers of spiniform setae on the pereopod 4-6 dactylus. Paragathotanais triunguisus can be separated from all other species by the numbers of spiniform setae on the pereopod 4-6 dactyli and the lack of maxilliped endite setae. Paranarthrura coinbrai can be separated from most other species on the spines on the propodi and ungues of pereopods 4-6. A key is given to the agathotanaids in the Antarctic/Subantarctic sector. This brings the number of agathotanaid species recorded from the Subantarctic and Antarctic sectors of the Atlantic to nine. PMID- 26131525 TI - Review of the systematics, biology and ecology of lice from pinnipeds and river otters (Insecta: Phthiraptera: Anoplura: Echinophthiriidae). AB - We present a literature review of the sucking louse family Echinophthiriidae, its five genera and twelve species parasitic on pinnipeds (fur seals, sea lions, walruses, true seals) and the North American river otter. We give detailed synonymies and published records for all taxonomic hierarchies, as well as hosts, type localities and repositories of type material; we highlight significant references and include comments on the current taxonomic status of the species. We provide a summary of present knowledge of the biology and ecology for eight species. Also, we give a host-louse list, and a bibliography to the family as complete as possible. PMID- 26131526 TI - Redescription of Microprosthema semilaeve (von Martens, 1872) (Decapoda: Stenopodidea: Spongicolidae) and description of a new species of Microprosthema from Dry Tortugas, Florida. AB - Microprosthema semilaeve, a fairly common spongicolid shrimp of reefal habitats in the Western Atlantic and Caribbean is redescribed and figured based on type material and an additional 78 specimens from the majority of its known zoogeographical range. It is distinguished from the Indo-Pacific species of M. validum and an undescribed species of Microprosthema with which it has been confused in the literature by a number of morphological characters. A new species of Microprosthema from deeper waters off the Dry Tortugas and closely related to M. inornatum Manning & Chace, 1990, is described and illustrated. Microprosthema jareckii Martin, 2002 is synonymized with M. manningi Goy & Felder, 1988. A key to the Western Atlantic species of Microprosthema is presented. PMID- 26131527 TI - The type species of Eucosma Hubner (Lepidoptera: Tortricidae: Eucosmini). AB - Eucosma Hubner is the largest genus in the Tortricidae with more than 290 named species. Historically, there has been confusion about the assignment of species to Eucosma and related genera, a problem which is perpetuated by the lack of a type specimen for the type species, E. circulana Hubner. Here we designate a neotype for E. circulana following analysis of eight North American species having similarities with that taxon. Eucosma circulana and E. gemellana Heinrich are redescribed, the latter being elevated from subspecies to species status. Eucosma paragemellana, new species, is described from specimens previously confused with E. gemellana, and E. fraudabilis Heinrich is reviewed. PMID- 26131528 TI - Four new Chlaenius species (Coleoptera: Carabidae: Chlaeniini) from Asia and a key to the species of subgenus Chlaenioctenus. AB - Four new Chlaenius species are described from Asian region: C. cheni Liu & Liang sp. n., C. bodhidharma Liu & Liang sp. n., C. li Liu & Liang sp. n., and C. aodai Liu & Liang sp. n. Chlaenius langsonensis Kirschenhofer, 2008 is assigned from subgenus Ocybatus to Chlaenioctenus. Chlaenius (Chlaenioctenus) eneides Bates, 1892 is redescribed and lectotype is designated. A key to all species of the subgenus Chlaenioctenus is provided. PMID- 26131529 TI - New species of Ameletus Eaton, 1885 and redescription of Ameletus longulus Sinichenkova, 1981 from the Russian Far East (Ephemeroptera: Ameletidae). AB - Ameletus khasanensis sp. nov. is described and Ameletus longulus Sinichenkova, 1981 is revalidated and redescribed based on material from the Russian Far East. The structure of the penis of both species is similar to that of Ameletus costalis (Matsumura 1931), a description and drawings of which are also presented in this paper. The male imago of A. khasanensis sp. nov. can be distinguished from that of A. costalis by the absence of spinules on the dorsal surface of the fore tibia. The male imago of A. longulus can be distinguished from A. khasanensis sp. nov. and A. costalis by the color of the forewings. The larvae of A. khasanensis sp. nov. differ from A. costalis in the length of the denticles on the right mandible, in the absence of the group of setae on the dorsal surface at the base of fore femora and the width/length ratio of gill VII. The larvae of A. longulus differ from A. khasanensis and A. costalis in the form and number of the denticles of the first comb-shaped seta of the maxilla and the number of setae on the dorsal surface of the base of the fore femora. PMID- 26131530 TI - A new genus of oak gallwasp, Cyclocynips Melika, Tang & Sinclair (Hymenoptera: Cynipidae: Cynipini), with descriptions of two new species from Taiwan. AB - A new genus of cynipid oak gallwasp-Cyclocynips Melika, Tang, & Sinclair (Hymenoptera: Cynipidae: Cynipini), with two new species--C. uberis and C. tumorvirgae--reared from galls on oaks of the Quercus subgenus Cyclobalanopsis is described from Taiwan. Descriptions of asexual generation adults and their diagnostic characters are presented. The likelihood of yet undiscovered sexual generations and the evolution of host-plant associations in these species are discussed. PMID- 26131531 TI - Two new species of Amblypsilopus Bigot with a key to species from Vietnam (Diptera: Dolichopodidae). AB - Eight species of the genus Amblypsilopus Bigot are now recorded from Vietnam. The following two new species are described: Amblypsilopus lacduonganus sp. nov. and A. longus sp. nov. Two species, A. basalis Yang and A. capitatus Yang, are newly reported from Vietnam. A key to the species of the genus from Vietnam is provided. PMID- 26131532 TI - A new species of the genus Tripylina Brzeski, 1963 (Nematoda: Enoplida: Trischistomatidae) from Shanxi province, China. AB - Tripylina puxianensis n. sp. is described and illustrated from Shanxi province, China. It is characterized by having a triangular dorsal tooth, pointing towards the ventral side, anterior to two sub-ventral teeth, with dorsal and sub-ventral teeth similar in shape and size; one ventromedian seta in the cervical region; vulva with protruding lips, absence of post-uterine sac; and a pair of setae on the tail; male not found; female body length 1048-1331 um, a = 25.5-33.8, b = 5.5 6.2, c = 14.4-23.1, c' = 2.1-3.5 and V = 56.1-68.5%. The phylogenetic relationships among species in the genus Tripylina were analyzed using data from the SSU (small subunit) and D2/D3 expansion segments of the LSU (large subunit) rDNA. These analyses confirmed that T. puxianensis n. sp. is different from other members of the genus for which sequences are available. PMID- 26131533 TI - Redescription of Alonella lineolata Sars, 1901 (Crustacea, Cladocera, Chydoridae) and its translocation to the subfamily Aloninae and to the new genus Bergamina gen. nov. AB - Alonella lineolata Sars 1901 (Anomopoda, Chydoridae) was described from a single female found in an aquarium prepared with dried mud from Sao Paulo, Brazil, and just recently this taxon has been reported again. The taxonomic status of A. lineolata was previously questioned, but re-evaluation was not possible until now due to the lack of specimens. The present paper described parthenogenetic females, based on specimens collected in a small pond at Prad6polis, state of Sao Paulo, and a specimen was selected as neotype. The head pores, mandibles, and the trunk limb morphology revealed that this species belongs to the subfamily Aloninae, instead of Chydorinae, as presumed by Sars. Despite its Alona-like aspect, this species presents a unique combination of characters, leading to its assignment to a new alonine genus, Bergamina gen. nov. PMID- 26131534 TI - New family host and records of Acanthocrios furnarii (Cordero & Vogelsang, 1928) (Hemiptera: Cimicidae) from Argentina, and implications in the transmission mechanism of cimicid bugs among birds' nests. AB - Acanthocrios furnarii (Cordero & Vogelsang, 1928) [Hemiptera: Cimicidae: Haematosiphoninae] is an ectoparasite on avian hosts from Argentina and Uruguay. It has been mostly found in mud nests of Furnarius rufus (Gmelin, 1788) [Aves: Furnariidae], but its true hosts are some of the inquiline birds that use F. rufus nests. These inquiline hosts belong to the families Emberizidae, Hirundinidae, Icteridae, Passeridae, and Troglodytidae. Outside F. rufus mud nests, A. furnarii has been found in nests of other Furnariidae, Hirundinidae, and Passeridae. The present work adds the first nonpasserine host (Falconidae) of A. furnarii, together with new records in La Pampa, Argentina. The transmission mechanism of A. furnarii, together with all other cimicid bugs from Argentina and adjacent countries, is increased considering this new host; and we also take into account the birds that nidificate in nest boxes, the cavity-nesting birds in trees and earth, and the inquiline birds in stick nests of Furnariidae and Psittacidae. PMID- 26131535 TI - Sexual dichromatism in a Mexican checkered beetle (Coleoptera: Cleridae: Neorthopleurinae). PMID- 26131536 TI - The genus Aeolothrips in Iran (Thysanoptera: Aeolothripidae) with one new species. AB - Aeolothrips zurstrasseni sp. n. is described from Fars Province, and A. modestus zur Strassen is newly recorded from Iran, in Isfahan Province. Both species have been collected from the flowers of Suaeda sp. (Chenopodiaceae), and the presence of several species of thrips on plants of this family is discussed. Recent records of Aeolothrips balati and A. citricinctus from Iran are not accepted here. PMID- 26131537 TI - Reforming emergency care: Experts put focus on value, better alignment. AB - While most healthcare reforms have thus far been focused outside of the ED, they nonetheless have big implications for emergency providers, according to a panel of experts who discussed the future of emergency care at a conference sponsored by the Brookings Institution in Washington, DC. Going forward, the experts noted that emergency providers need to engage on how to most-effectively deliver higher value while also achieving better alignment with primary care providers. And they highlighted reforms that are already delivering results in pioneering EDs. Through the use of high-risk care plans, a specialized protocol for chest pain, and other reforms, the ED at the University of Maryland Upper Chesapeake Health System, based in Bel Air, MD, has been able to prevent more than 500 hospital admissions in the past year. Working with partners, emergency physicians in Washington state have managed to save the state more than $32 million while also slashing narcotic prescribing to Medicaid recipients by 24%. Their interventions include a prescription drug monitoring program, a mechanism for information sharing on key data points, and the development of care plans for frequent ED utilizers. A program called Bridges to Care in Denver, CO, has thus far been able to reduce ED and hospital utilization among frequent utilizers by 40%, generating $2 million in cost-savings to the health care system. The program focuses on identifying the key drivers of utilization, and then addressing these drivers with interventions. Program developers say connecting with patients while they are still in the ED, as opposed to making follow-up phone calls, is key to the program's success. PMID- 26131538 TI - Ease crowding by adjusting physician schedules, adding a second rounding team. AB - A new study highlights how schedule changes among inpatient providers on the upper floors can impact crowding and boarding in the ED. Using Lean Six Sigma (LSS) management techniques, investigators at Penn State Hershey Children's Hospital in Hershey, PA, discovered that by adding an extra inpatient rounding team, discharge times could be accelerated, resulting in improved throughput without increasing length of stay or readmission rates. Data show that the scheduling adjustments enabled the hospital to slash 90 minutes off discharge times when compared with usual care. The scheduling changes enabled the hospital to discharge 45% more patients per day without increasing length-of-stay or readmission rates. To make the schedule changes, a core group of seven inpatient physicians needed to agree to work an extra two or three "on service" weeks per year. Investigators acknowledge that implementing this type of intervention requires culture change, which can be very difficult initially. PMID- 26131539 TI - Kidney stone patients often require return visits; researchers target access, care quality issues. AB - With the incidence of kidney stone disease on the rise, more of these patients are presenting to EDs for care. However, new data suggest that as many as one in nine of these patients will have to return for a second emergency visit. Researchers have linked a number of factors with these bounce-back visits, including issues impacting care access and quality. The incidence of kidney stone disease has nearly doubled in the past 15 years, with more than one million patients seeking care in the ED every year. Utilizing data from more than 128,000 visits to California EDs over a two-year period, researchers found that patients on Medicaid were at about a 50% higher risk of having a repeat ED visit than patients with commercial insurance. In areas where there were few urologists, patients were also more likely to return to the ED for care. Patients who had their blood counts checked during their initial ED visit were 12% less likely to require a return visit. PMID- 26131549 TI - Patriline Differences Reveal Genetic Influence on Forewing Size and Shape in a Yellowjacket Wasp (Hymenoptera: Vespidae: Vespula flavopilosa Jacobson, 1978). AB - The wing venation is frequently used as a morphological marker to distinguish biological groups among insects. With geometric morphometrics, minute shape differences can be detected between closely related species or populations, making this technique useful for taxonomy. However, the direct influence of genetic differences on wing morphology has not been explored within colonies of social insects. Here, we show that the father's genotype has a direct effect on wing morphology in colonies of social wasps. Using geometric morphometrics on the venation pattern, we found significant differences in wing size and shape between patrilines of yellowjackets, taking allometry and measurement error into account. The genetic influence on wing size accounted for a small part of the overall size variation, but venation shape was highly structured by the differences between patrilines. Overall, our results showed a strong genetic influence on wing morphology likely acting at multiple levels of venation pattern development. This confirmed the pertinence of this marker for taxonomic purposes and suggests this phenotype as a potentially useful marker for phylogenies. This also raises doubts about the strength of selective pressures on this phenotype, which highlights the need to understand better the role of wing venation shape in insect flight. PMID- 26131550 TI - Different Ecological Niches for Ticks of Public Health Significance in Canada. AB - Tick-borne diseases are a growing public health concern as their incidence and range have increased in recent decades. Lyme disease is an emerging infectious disease in Canada due to northward expansion of the geographic range of Ixodes scapularis, the principal tick vector for the Lyme disease agent Borrelia burgdorferi, into central and eastern Canada. In this study the geographical distributions of Ixodid ticks, including I. scapularis, and environmental factors associated with their occurrence were investigated in New Brunswick, Canada, where few I. scapularis populations have been found to date. Density of host seeking ticks was evaluated by drag sampling of woodland habitats in a total of 159 sites. Ixodes scapularis ticks (n = 5) were found on four sites, Ixodes muris (n = 1) on one site and Haemaphysalis leporispalustris (n = 243) on 41 sites. One of four adult I. scapularis ticks collected was PCR-positive for B. burgdorferi. No environmental variables were significantly associated with the presence of I. scapularis although comparisons with surveillance data in neighbouring provinces (Quebec and Nova Scotia) suggested that temperature conditions may be too cold for I. scapularis (< 2800 annual degree days above 0 degrees C [DD > 0 degrees C]) across much of New Brunswick. In contrast, the presence of H. leporispalustris, which is a competent vector of tularaemia, was significantly (P < 0.05) associated with specific ranges of mean DD > 0 degrees C, mean annual precipitation, percentage of clay in site soil, elevation and season in a multivariable logistic regression model. With the exception of some localized areas, temperature conditions and deer density may be too low for the establishment of I. scapularis and Lyme disease risk areas in New Brunswick, while environmental conditions were suitable for H. leporispalustris at many sites. These findings indicate differing ecological niches for two tick species of public health significance. PMID- 26131551 TI - Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. AB - The platinum-based anticancer drug oxaliplatin is important clinically in cancer treatment. However, the role of multidrug resistance-associated protein 2 (MRP2) in controlling oxaliplatin membrane transport, in vivo handling, toxicity and therapeutic responses is unclear. In the current study, preparations of MRP2 expressing and control membrane vesicles, containing inside-out orientated vesicles, were used to directly characterise the membrane transport of oxaliplatin-derived platinum measured by inductively coupled plasma mass spectrometry. Oxaliplatin inhibited the ATP-dependent accumulation of the model MRP2 fluorescent probe, 5(6)-carboxy-2,'7'-dichlorofluorescein, in MRP2 expressing membrane vesicles. MRP2-expressing membrane vesicles accumulated up to 19-fold more platinum during their incubation with oxaliplatin and ATP as compared to control membrane vesicles and in the absence of ATP. The rate of ATP dependent MRP2-mediated active transport of oxaliplatin-derived platinum increased non-linearly with increasing oxaliplatin exposure concentration, approaching a plateau value (Vmax) of 2680 pmol Pt/mg protein/10 minutes (95%CI, 2010 to 3360 pmol Pt/mg protein/10 minutes), with the half-maximal platinum accumulation rate (Km) at an oxaliplatin exposure concentration of 301 MUM (95% CI, 163 to 438 MUM), in accordance with Michaelis-Menten kinetics (r2 = 0.954). MRP2 inhibitors (myricetin and MK571) reduced the ATP-dependent accumulation of oxaliplatin-derived platinum in MRP2-expressing membrane vesicles in a concentration-dependent manner. To identify whether oxaliplatin, or perhaps a degradation product, was the likely substrate for this active transport, HPLC studies were undertaken showing that oxaliplatin degraded slowly in membrane vesicle incubation buffer containing chloride ions and glutathione, with approximately 95% remaining intact after a 10 minute incubation time and a degradation half-life of 2.24 hours (95%CI, 2.08 to 2.43 hours). In conclusion, MRP2 mediates the ATP-dependent active membrane transport of oxaliplatin-derived platinum. Intact oxaliplatin and its anionic monochloro oxalate ring-opened intermediate appear likely candidates as substrates for MRP2-mediated transport. PMID- 26131552 TI - Diversity and Persistence of Salmonella enterica Strains in Rural Landscapes in the Southeastern United States. AB - Salmonellosis cases in the in the United States show distinct geographical trends, with the southeast reporting among the highest rates of illness. In the state of Georgia, USA, non-outbreak associated salmonellosis is especially high in the southern low-lying coastal plain. Here we examined the distribution of Salmonella enterica in environmental waters and associated wildlife in two distinct watersheds, one in the Atlantic Coastal Plain (a high case rate rural area) physiographic province and one in the Piedmont (a lower case rate rural area). Salmonella were isolated from the two regions and compared for serovar and strain diversity, as well as distribution, between the two study areas, using both a retrospective and prospective design. Thirty-seven unique serovars and 204 unique strain types were identified by pulsed-field gel electrophoresis (PFGE). Salmonella serovars Braenderup, Give, Hartford, and Muenchen were dominant in both watersheds. Two serovars, specifically S. Muenchen and S. Rubislaw, were consistently isolated from both systems, including water and small mammals. Conversely, 24 serovars tended to be site-specific (64.8%, n = 37). Compared to the other Salmonella serovars isolated from these sites, S. Muenchen and S. Rubislaw exhibited significant genetic diversity. Among a subset of PFGE patterns, approximately half of the environmental strain types matched entries in the USA PulseNet database of human cases. Ninety percent of S. Muenchen strains from the Little River basin (the high case rate area) matched PFGE entries in PulseNet compared to 33.33% of S. Muenchen strains from the North Oconee River region (the lower case rate area). Underlying the diversity and turnover of Salmonella strains observed for these two watersheds is the persistence of specific Salmonella serovars and strain types that may be adapted to these watersheds and landscapes. PMID- 26131553 TI - High Incubation Temperature and Threonine Dietary Level Improve Ileum Response Against Post-Hatch Salmonella Enteritidis Inoculation in Broiler Chicks. AB - This study assessed the effect of both embryonic thermal manipulation and dietary threonine level on the response of broilers inoculated with Salmonella Enteritidis, considering bacterial counts in the cecal contents, intestinal morphology, mucin and heat shock protein 70 gene expression, body weight and weight gain. Thermal manipulation was used from 11 days of incubation until hatch, defining three treatments: standard (37.7 degrees C), continuous high temperature (38.7 degrees C) and continuous low temperature (36.7 degrees C). After hatch, chicks were distributed according to a 3x2+1 factorial arrangement (three temperatures and two threonine levels and one sham-inoculated control). At two days of age, all chicks were inoculated with Salmonella Enteritidis, except for the sham-inoculated control group. There was no interaction between the factors on any analyses. High temperature during incubation was able to reduce colonization by Salmonella Enteritidis in the first days, reducing both Salmonella counts and the number of positive birds. It also increased mucin expression and decreased Hsp70 expression compared with other inoculated groups. High temperature during incubation and high threonine level act independently to reduce the negative effects associated to Salmonella Enteritidis infection on intestinal morphology and performance, with results similar to sham-inoculated birds. The findings open new perspectives for practical strategies towards the pre-harvest Salmonella control in the poultry industry. PMID- 26131554 TI - Comparison of Two RapidArc Delivery Strategies in Stereotactic Body Radiotherapy of Peripheral Lung Cancer with Flattening Filter Free Beams. AB - PURPOSE: To investigate the performance of using partial arc (PA) and full arc with avoidance sectors (FAAS) in stereotactic body radiotherapy (SBRT) of peripheral lung cancer with flattening filter free (FFF) beams. METHODS: Eighteen patients with primary (T1 or T2) non-small-cell lung cancer (NSCLC) or lung metastatic were selected for this study. Nine patients with a gross tumor volume (GTV) <= 10 cc were designated as the small tumor group. The other nine patients with a GTV between 10 cc and 44 cc were assigned to the large tumor group. The treatment plans were generated in eighteen patients using PA and FAAS techniques, respectively, and delivered with a Varian TrueBeam Linac. Dosimetry of the target and organs at risk (OARs), monitor unit (MU), out-of-field dose, and delivery time were statistically analyzed. Delta4 and portal dosimetry were employed to evaluate the delivery accuracy. RESULTS: For the small tumor group, compared with the PA plans, the FAAS plans significantly achieved a lower MU/fraction, out-of field dose and a shorter treatment time (p<0.05), but the target dose was slightly higher than that delivered by PA plans (p<0.05). For the large tumor group, the PA plans significantly attained a shorter treatment time (p<0.05), whereas MU/fraction, out-of-field dose and dose to OARs were comparable between the two plans (p>0.05). Furthermore, all plans generated from the eighteen patients achieved a high pass rate in patient-specific quality assurance, with all the gamma indices greater than 97% at the Gamma3mm, 3% threshold. CONCLUSION: This study suggests that the FAAS technique is more beneficial for the small tumor patients undergoing lung SBRT with FFF beams because of its higher treatment efficiency and MU reduction. However, for the large tumor patients, the PA technique is recommended due to its higher treatment efficiency. PMID- 26131555 TI - Phylogenetic Analysis of Nucleus-Encoded Acetyl-CoA Carboxylases Targeted at the Cytosol and Plastid of Algae. AB - The understanding of algal phylogeny is being impeded by an unknown number of events of horizontal gene transfer (HGT), and primary and secondary/tertiary endosymbiosis. Through these events, previously heterotrophic eukaryotes developed photosynthesis and acquired new biochemical pathways. Acetyl-CoA carboxylase (ACCase) is a key enzyme in the fatty acid synthesis and elongation pathways in algae, where ACCase exists in two locations (cytosol and plastid) and in two forms (homomeric and heteromeric). All algae contain nucleus-encoded homomeric ACCase in the cytosol, independent of the origin of the plastid. Nucleus-encoded homomeric ACCase is also found in plastids of algae that arose from a secondary/tertiary endosymbiotic event. In contrast, plastids of algae that arose from a primary endosymbiotic event contain heteromeric ACCase, which consists of three nucleus-encoded and one plastid-encoded subunits. These properties of ACCase provide the potential to inform on the phylogenetic relationships of hosts and their plastids, allowing different hypothesis of endosymbiotic events to be tested. Alveolata (Dinoflagellata and Apicomplexa) and Chromista (Stramenopiles, Haptophyta and Cryptophyta) have traditionally been grouped together as Chromalveolata, forming the red lineage. However, recent genetic evidence groups the Stramenopiles, Alveolata and green plastid containing Rhizaria as SAR, excluding Haptophyta and Cryptophyta. Sequences coding for plastid and cytosol targeted homomeric ACCases were isolated from Isochrysis aff. galbana (TISO), Chromera velia and Nannochloropsis oculata, representing three taxonomic groups for which sequences were lacking. Phylogenetic analyses show that cytosolic ACCase strongly supports the SAR grouping. Conversely, plastidial ACCase groups the SAR with the Haptophyta, Cryptophyta and Prasinophyceae (Chlorophyta). These two ACCase based, phylogenetic relationships suggest that the plastidial homomeric ACCase was acquired by the Haptophyta, Cryptophyta and SAR, before the photosynthetic Rhizaria acquired their green plastid. Additionally, plastidial ACCase was derived by HGT from an ancestor or relative of the Prasinophyceae and not by duplication of cytosolic ACCase. PMID- 26131557 TI - Hierarchical Formation Mechanism of CoFe2O4 Mesoporous Assemblies. AB - The development of synthetic hybrid organic-inorganic approaches and the understanding of the chemico-physical mechanisms leading to hierarchical assembly of nanocrystals into superstructures pave the way to the design and fabrication of multifunction microdevices able to simultaneously control processes at the nanoscale. This work deals with the design of spherical mesoporous magnetic assemblies through a surfactant assisted water-based strategy and the study of the formation mechanism by a combined use of transmission electron microscopy, X ray diffraction, and time-resolved small angle X-ray scattering techniques. We visualize the hierarchical mechanism formation of the magnetic assemblies in the selected sodium dodecylsulfate (SDS)-assisted water-based strategy. At the first stage, an intermediate lamellar phase (L) represented by beta-Co(OH)2 and FeOOH hexagonal plates is formed. Then, the nucleation of primary CoFe2O4 (N1) nanocrystals of about 6-7 nm occurs by the dissolution of FeOOH and the reaction of Fe(III) ions coordinated to the SDS micelles, at the reactive sites provided by vertices and edges of the beta-Co(OH)2 plates. The intermediate phase consumes as the primary crystalline nanoparticles form, confined by the surfactant molecules around them, and assembly in spherical mesoporous assemblies. The key role of the surfactant in the formation of porous assemblies has been evidenced by an experiment carried out in the absence of SDS and confirmed by the pore size diameter of the assemblies (about 2-3 nm), that can be correlated with the length of the surfactant dodecylsulfate molecule. PMID- 26131556 TI - Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies. AB - Many protein-coding genes identified by genome sequencing remain without functional annotation or biological context. Here we define a novel protein coding gene, Nmf9, based on a forward genetic screen for neurological function. ENU-induced and genome-edited null mutations in mice produce deficits in vestibular function, fear learning and circadian behavior, which correlated with Nmf9 expression in inner ear, amygdala, and suprachiasmatic nuclei. Homologous genes from unicellular organisms and invertebrate animals predict interactions with small GTPases, but the corresponding domains are absent in mammalian Nmf9. Intriguingly, homozygotes for null mutations in the Drosophila homolog, CG45058, show profound locomotor defects and premature death, while heterozygotes show striking effects on sleep and activity phenotypes. These results link a novel gene orthology group to discrete neurological functions, and show conserved requirement across wide phylogenetic distance and domain level structural changes. PMID- 26131558 TI - Mouse Hepatic Tumor Vascular Imaging by Experimental Selective Angiography. AB - PURPOSE: Human hepatocellular carcinoma (HCC) has unique vascular features, which require selective imaging of hepatic arterial perfusion and portal venous perfusion with vascular catheterization for sufficient evaluation. Unlike in humans, vessels in mice are too small to catheterize, and the importance of separately imaging the feeding vessels of tumors is frequently overlooked in hepatic tumor models. The purpose of this study was to perform selective latex angiography in several mouse liver tumor models and assess their suitability. MATERIALS AND METHODS: In several ectopic (Lewis lung carcinoma, B16/F10 melanoma cell lines) and spontaneous liver tumor (Albumin-Cre/MST1fl/fl/MST2fl/fl, Albumin Cre/WW45fl/fl, and H-ras12V genetically modified mouse) models, the heart left ventricle and/or main portal vein of mice was punctured, and latex dye was infused to achieve selective latex arteriography and/or portography. RESULTS: H ras12V transgenic mice (a HCC and hepatic adenoma model) developed multiple liver nodules that displayed three different perfusion patterns (portal venous or hepatic artery perfusion predominant, mixed perfusion), indicating intra-tumoral vascular heterogeneity. Selective latex angiography revealed that the Lewis lung carcinoma implant model and the Albumin-Cre/WW45fl/fl model reproduced conventional angiography findings of human HCC. Specifically, these mice developed tumors with abundant feeding arteries but no portal venous perfusion. CONCLUSION: Different hepatic tumor models showed different tumor vessel characteristics that influence the suitability of the model and that should be considered when designing translational experiments. Selective latex angiography applied to certain mouse tumor models (both ectopic and spontaneous) closely simulated typical characteristics of human HCC vascular imaging. PMID- 26131559 TI - Correction: Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling. PMID- 26131560 TI - Accuracy of the anthropometric measurements of skeletonized skulls with corresponding measurements of their 3D reconstructions obtained by CT scanning. AB - BACKGROUND: The anthropometric measurements of the skeletonized skull are crucial in the investigation of human remains, mostly for personal identification. The images of the skull are used if the superimposition or approximation of the facial appearance is to be performed. The aim of the study was to compare the accuracy of the anthropometric measurements of skeletonized skulls with corresponding measurements of their 3D reconstructions obtained by CT scanning. METHODS: Ten skeletonized skulls and their 3D digital reconstructions were measured according to standard anthropometric procedures. The results were compared and statistical analysis was performed. RESULTS: The statistical analysis revealed that the 3D reconstruction is absolutely reliable for any measurements within the skull. The results of the measurements obtained from the CT image were accurate and comparable to the results of the anthropometric analysis of the skeletonized skull. The correlation between the anthropometry of the skeletonized skulls and the CT reconstructions was strong. CONCLUSIONS: It is relevant that 3D reconstructions of the skull can be used in forensic anthropology for personal identification. PMID- 26131562 TI - A Collision Probability Model of Portal Vein Tumor Thrombus Formation in Hepatocellular Carcinoma. AB - Hepatocellular carcinoma is one of the most common malignancies worldwide, with a high risk of portal vein tumor thrombus (PVTT). Some promising results have been achieved for venous metastases of hepatocellular carcinoma; however, the etiology of PVTT is largely unknown, and it is unclear why the incidence of PVTT is not proportional to its distance from the carcinoma. We attempted to address this issue using physical concepts and mathematical tools. Finally, we discuss the relationship between the probability of a collision event and the microenvironment of the PVTT. Our formulae suggest that the collision probability can alter the tumor microenvironment by increasing the number of tumor cells. PMID- 26131561 TI - Organization of the multiaminoacyl-tRNA synthetase complex and the cotranslational protein folding. AB - Aminoacyl-tRNA synthetases (ARSs) play an essential role in the protein synthesis by catalyzing an attachment of their cognate amino acids to tRNAs. Unlike their prokaryotic counterparts, ARSs in higher eukaryotes form a multiaminoacyl-tRNA synthetase complex (MARS), consisting of the subset of ARS polypeptides and three auxiliary proteins. The intriguing feature of MARS complex is the presence of only nine out of twenty ARSs, specific for Arg, Asp, Gln, Glu, Ile, Leu, Lys, Met, and Pro, regardless of the organism, cell, or tissue types. Although existence of MARSs complex in higher eukaryotes has been already known for more than four decades, its functional significance remains elusive. We found that seven of the nine corresponding amino acids (Arg, Gln, Glu, Ile, Leu, Lys, and Met) together with Ala form a predictor of the protein alpha-helicity. Remarkably, all amino acids (besides Ala) in the predictor have the highest possible number of side-chain rotamers. Therefore, compositional bias of a typical alpha-helix can contribute to the helix's stability by increasing the entropy of the folded state. It also appears that position-specific alpha-helical propensity, specifically periodic alternation of charged and hydrophobic residues in the helices, may well be provided by the structural organization of the complex. Considering characteristics of MARS complex from the perspective of the alpha-helicity, we hypothesize that specific composition and structure of the complex represents a functional mechanism for coordination of translation with the fast and correct folding of amphiphilic alpha-helices. PMID- 26131563 TI - Reliability of Nationwide Prevalence Estimates of Dementia: A Critical Appraisal Based on Brazilian Surveys. AB - BACKGROUND: The nationwide dementia prevalence is usually calculated by applying the results of local surveys to countries' populations. To evaluate the reliability of such estimations in developing countries, we chose Brazil as an example. We carried out a systematic review of dementia surveys, ascertained their risk of bias, and present the best estimate of occurrence of dementia in Brazil. METHODS AND FINDINGS: We carried out an electronic search of PubMed, Latin-American databases, and a Brazilian thesis database for surveys focusing on dementia prevalence in Brazil. The systematic review was registered at PROSPERO (CRD42014008815). Among the 35 studies found, 15 analyzed population-based random samples. However, most of them utilized inadequate criteria for diagnostics. Six studies without these limitations were further analyzed to assess the risk of selection, attrition, outcome and population bias as well as several statistical issues. All the studies presented moderate or high risk of bias in at least two domains due to the following features: high non-response, inaccurate cut-offs, and doubtful accuracy of the examiners. Two studies had limited external validity due to high rates of illiteracy or low income. The three studies with adequate generalizability and the lowest risk of bias presented a prevalence of dementia between 7.1% and 8.3% among subjects aged 65 years and older. However, after adjustment for accuracy of screening, the best available evidence points towards a figure between 15.2% and 16.3%. CONCLUSIONS: The risk of bias may strongly limit the generalizability of dementia prevalence estimates in developing countries. Extrapolations that have already been made for Brazil and Latin America were based on a prevalence that should have been adjusted for screening accuracy or not used at all due to severe bias. Similar evaluations regarding other developing countries are needed in order to verify the scope of these limitations. PMID- 26131564 TI - Complaints and Diagnoses of Emergency Department Patients in the Netherlands: A Comparative Study of Integrated Primary and Emergency Care. AB - OBJECTIVE: In the Netherlands, an increasing number of emergency departments (EDs) and general practitioner cooperatives collaborate by creating one Emergency Care-Access-Point (ECAP). This has resulted in fewer patients at ECAP EDs. The objective of this study was to explore differences in patient characteristics, presented complaints and ED discharge diagnoses between EDs with an ECAP and EDs without an ECAP. METHODS: A retrospective observational study was performed with 1800 consecutive patient records sampled from six EDs spread over the Netherlands in 2013. We extracted data on time and date of presentation, sex, age, presenting complaint, discharge diagnosis, origin and follow up. RESULTS: At ECAP EDs, the mean age was 47.8 years (95%CI 46.1-49.4) compared to 41.3 (95%CI 39.7-42.9). Compared to non-ECAP EDs, more patients were referred by medical professionals (74.7% versus 46.8%), more patients received hospital admission (45.2% versus 29.0%) and fewer patients received GP follow-up (4.1% versus 16.9%). There was no significant difference in presenting complaints between ECAP and non-ECAP EDs. Most prevalent complaints were trauma (25.7% versus 29.7%), abdominal pain (12.1% versus 10.9%) and general symptoms (7.8% versus 4.8%). The most prevalent ED diagnoses significantly differed with fractures and dislocations (10.8%), sprains and strains (10.4%) and respiratory infections (6.8%) at ECAP EDs versus fractures and dislocations (10.7%), wounds (9.3%) and sprains and strains (8.9%) at non-ECAP EDs. CONCLUSION: Compared to non-ECAP EDs, patients at ECAP EDs were older, medical professionals referred more patients and more patients received a hospital admission. We found some small differences in discharge diagnoses between ECAP EDs compared to non-ECAP EDs, but no difference in presented complaints. PMID- 26131565 TI - Prognostic Factors for Reoperation After Plate Fixation of the Midshaft Clavicle. AB - OBJECTIVES: To determine which prognostic factors were associated with an increased risk for all-cause reoperation in a heterogeneous population of patients treated with primary plate fixation of a midshaft clavicular fracture. DESIGN: Retrospective observational study. SETTING: Single university-affiliated tertiary care Level 1 trauma center. PATIENTS: Of 235 consecutive patients with primary plate fixation for a midshaft clavicular fracture. A reviewer extracted data through a retrospective chart review regarding 20 possible prognostic variables and documented reoperations (defined as any surgical procedure after the initial surgery, including implant removal, bone grafts, implant exchanges, or debridement for infection). INTERVENTION: Open reduction and internal fixation of the clavicle using straight and precontoured clavicle plates. MAIN OUTCOME MEASUREMENTS: Complete 2-year follow-up information was available for 153 of 235 patients (65%). Of these 153 patients included in the analysis, 58 (38%) had reoperations. The preoperative risk factors for 3 specific "reoperation outcomes" were examined: (1) reoperation for implant removal alone; (2) reoperation for nonunion, infection, or fixation failure; and (3) multiple reoperations. RESULTS: There was a significant reoperation rate in this patient series (58 of 153 patients, 38%). Although most were for isolated plate removal (42 of 153 patients, 27%), there were a minority of patients who required more complex (16 of 153 patients, 10%) or multiple (8 of 153 patients, 5%) procedures. For these 3 possible outcomes (reoperation for implant removal alone, reoperation for nonunion, infection, or fixation failure, and the need for multiple reoperations), significant risk factors were identified that can assist surgeons in patient selection and predicting reoperation after plate fixation of midshaft clavicle fractures. The significant risk factors for implant removal alone (42 of 153, 27%) were the use of a plate that was not precontoured and patient height <175 cm. The significant risk factors for reoperation for nonunion, infection, or fixation failure (16 of 153, 10%) were illicit drug use, diabetes, and previous surgery of the shoulder. The significant risk factors for multiple reoperations (8 of 153, 5%) were age >55 years and alcohol use >15 drinks per week. CONCLUSIONS: The use of precontoured plates can decrease the rate of hardware removal after primary fixation of displaced fractures of the midshaft clavicle. Also, specific preoperative prognostic factors may be used to counsel patients, maximize outcomes, minimize serious complications, and limit revision surgery. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 26131566 TI - Efficacy of Routine Postoperative CT Scan After Open Reduction and Internal Fixation of the Acetabulum. AB - OBJECTIVES: The purpose of this study was to evaluate the efficacy of routine postoperative computed tomography (CT) scan after open reduction and internal fixation of acetabular fractures. DESIGN: Retrospective review of prospectively collected acetabulum fracture database. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: A total of 606 consecutive patients underwent surgical fixation of 612 acetabular fractures. All patients were evaluated with intraoperative fluoroscopy in addition to 3 standard plain radiographs (AP pelvis and two 45 degrees oblique Judet views). Reduction and fixation were believed to be adequate and definitive before exiting the operative suite based on these imaging modalities. INTERVENTION: Axial postoperative CT scan of the pelvis was obtained in 563 of the patients (93%) after 569 operative cases. MAIN OUTCOME MEASUREMENTS: Revision acetabular surgery based on routine postoperative CT scan findings. RESULTS: There were no significant differences between index and revision surgery groups regarding age, gender, body mass index, fracture pattern, mechanism of injury, or surgical approach (P > 0.05). Evaluation of 563 postoperative CT scans of the pelvis resulted in revision acetabular surgery for 2.5% of patients (n = 14). There were 6 (1.1%) cases of intraarticular hardware not recognized on the intraoperative fluoroscopy or pelvic radiographs. Four patients (0.7%) had residual intraarticular osteochondral fragments deemed too large to leave in the hip joint. There were 3 cases (0.5%) of unacceptable malreduction, and 1 case (0.2%) of both malreduction and an intraarticular osteochondral fragment. CONCLUSIONS: A small percentage of patients (2.5%) will benefit from a routine CT scan after acetabular fracture fixation. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26131567 TI - How to Use Fluoroscopic Imaging to Prevent Intraarticular Screw Perforation During Locked Plating of Proximal Humerus Fractures: A Cadaveric Study. AB - OBJECTIVE: Intraarticular screw perforation is a common complication of open reduction and internal fixation of proximal humerus fractures. The purpose of this study was to (1) determine the sensitivity and specificity of the fluoroscopic images used to evaluate whether a screw tip has perforated into the glenohumeral joint, and (2) determine the specific fluoroscopic views that best evaluate screw position in the humeral head. METHODS: Twenty-two proximal humeri in 11 lightly embalmed cadavers were instrumented. The articular surface was divided into equal-sized rows (superior, central, inferior) and columns (anterior, middle, posterior). The screws in 10 humeri were inserted and so their tips were located 2 mm beneath the articular surface. Twelve humeri had screws placed such that their tips protruded 2 mm past the articular surface into the glenohumeral joint. Twenty-seven different C-arm views were obtained of each specimen/screw configuration. RESULTS: There were zero false-positives (100% specificity). The average sensitivity was 55% and varied greatly depending on the image view and the screw exit location (range, 0%-100%). The sensitivity for the inferior row of screws was the lowest (39.1%) and was particularly low for the posterior-inferior screw exit location (20.7%). CONCLUSIONS: Screws that are completely located within the bone of the proximal humerus will never appear on C arm images as intraarticular. However, screws that are intraarticular may appear to be completely located within the bone of the proximal humerus on some C-arm images. A sensitivity of 100% for detecting intraarticular screws for 8 of the 9 screws' exit locations and 90% for the posterior-inferior screw can be achieved by imaging the proximal humerus in 25-degree internal rotation, neutral, and 25 degree external rotation with the C-arm in neutral cant at rainbow 25-degree roll over, neutral rainbow, and rainbow 25-degree roll back for a total of 9 images. PMID- 26131568 TI - Traumatic Posterior Atlantoaxial Dislocation Without Fracture of Odontoid Process: A Case Report and Systematic Analysis of 19 Cases. AB - OBJECTIVES: To evaluate the ideal treatment strategy for traumatic posterior atlantoaxial dislocation without fracture of odontoid process. DESIGN: Case report and systematic analysis based on the methodology of evidence-based medicine. SETTING: Level IV trauma center. PATIENTS: Nineteen patients who suffered from traumatic posterior atlantoaxial dislocation without fracture of odontoid process. INTERVENTION: Closed reduction, open reduction, internal fixation, and fusion. OUTCOME MEASURES: Neurologic status, range of motion, and radiographs for stability or fusion. RESULTS: Nineteen cases were included in this analysis. The mean age was 37.7 +/- 13.8 years (range, 20-65 years). Sixteen cases (84%) were male, and 3 cases (16%) were female. Thirteen cases (68%) have a transient loss of consciousness. Ten cases (53%) presented no neurologic deficits. All 9 patients (47%) with neurologic deficits recovered without any residual deficits. Eleven dislocations (58%) were reduced by closed reduction, followed by fusion in 5 of them (45%), and the remaining 6 dislocations (55%) were treated conservatively. Eight dislocations (42%) were treated by open reduction and fusion. CONCLUSIONS: Traumatic posterior atlantoaxial dislocation without fracture of odontoid process usually presents without a severe neurologic deficit. Even if it presents with mild or transient neurologic deficit, it would be restored without any residual deficits. Closed reduction is usually successful and safe. The need for fusion after successful closed reduction depends on the integrity of the transverse ligament and the stability of cervical spine. If anatomic reduction is not achieved by closed reduction, open reduction and fusion should be performed. PMID- 26131569 TI - Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect. AB - Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these strategies is to examine their effects on heart function. There are several techniques to measure in vivo cardiac mechanics (e.g., echocardiography, pressure/volume relations, etc.). Compared to echocardiography, real-time left ventricular (LV) pressure/volume analysis via catheterization is more precise and insightful in assessing LV function. Additionally, LV pressure/volume analysis provides the ability to instantaneously record changes during manipulations of contractility (e.g., beta-adrenergic stimulation) and pathological insults (e.g., ischemia/reperfusion injury). In addition to the maximum (+dP/dt) and minimum ( dP/dt) rate of pressure change in the LV, an accurate assessment of LV function via several load-independent indexes (e.g., end systolic pressure volume relationship and preload recruitable stroke work) can be attained. Heart rate has a significant effect on LV contractility such that an increase in the heart rate is the primary mechanism to increase cardiac output (i.e., Bowditch effect). Thus, when comparing hemodynamics between experimental groups, it is necessary to have similar heart rates. Furthermore, a hallmark of many cardiomyopathy models is a decrease in contractile reserve (i.e., decreased Bowditch effect). Consequently, vital information can be obtained by determining the effects of increasing heart rate on contractility. Our and others data has demonstrated that the neuronal nitric oxide synthase (NOS1) knockout mouse has decreased contractility. Here we describe the procedure of measuring LV pressure/volume with increasing heart rates using the NOS1 knockout mouse model. PMID- 26131570 TI - Federal Health Coverage Mandates and Health Care Utilization: The Case of the Women's Health and Cancer Rights Act and Use of Breast Reconstruction Surgery. AB - BACKGROUND: Utilization of breast reconstruction services remains low among women who underwent mastectomy despite the improvement in quality of life associated with this treatment. The objective of this study is to identify the effect of the Women's Health and Cancer Rights Act (WHCRA)-an understudied ongoing federal law that mandated insurance coverage of breast reconstruction following mastectomy beginning in 1999-on use of reconstructive surgery after mastectomy. METHODS: We use a difference-in-differences (DD) approach to identify the change in breast reconstruction utilization induced by WHCRA by comparing the pre- and post-policy changes in utilization between states that did not have existing laws mandating coverage before the WHCRA (treatment group) and those that had such state laws (control group). The data are from the Surveillance, Epidemiology, and End Results program. The main sample includes 15,737 female patients who were under the age of 64 and underwent mastectomy within 4 months of diagnosis of early stage breast cancer during 1998 and 2000. RESULTS: Based on the DD model, the odds of using reconstruction services in the states without preexisting laws increased after the WHCRA by 31% in 1999 and 36% in 2000 (compared with 1998 before the WHCRA). These effects are masked in a simple pre/post model for change in reconstruction across all states. Additional analyses through 2007 indicate that the WHCRA had long-term effects on utilization. Furthermore, analyses by state indicate that most states in the treatment group experienced a significance increase in utilization. CONCLUSIONS: The use of breast reconstruction after mastectomy significantly increased after the WHCRA. At a minimum, our estimates may be considered the lower bound of the real policy effect. PMID- 26131571 TI - Laughter as a scientific problem: An adventure in sidewalk neuroscience. AB - Laughter is a stereotyped, innate, human play vocalization that provides an ideal simple system for neurobehavioral analyses of the sort usually associated with such animal models as walking, wing-flapping, and bird song. Laughter research is in its early stages, where the frontiers are near and accessible to simple observational procedures termed "sidewalk neuroscience." The basic, nontechnical approach of describing the act of laughter and when humans do it has revealed a variety of phenomena of social and neurological significance. Findings include the acoustic structure of laughter, the minimal voluntary control of laughter, contagiousness, the "punctuation effect" that describes the placement of laughter in conversation, the dominance of speech over laughter, the role of breath control in the evolution of speech, the evolutionary trajectory of laughter in primates, and the role of laughter in human matching and mating. If one knows where to look and how to see, advances in neuroscience are accessible to anyone and require minimal resources. PMID- 26131572 TI - Insulin-like growth factor-1 receptor (IGF-1R) inhibition promotes expansion of human NK cells which maintain their potent antitumor activity against Ewing sarcoma cells. AB - BACKGROUND: Patients with primary metastatic or relapsed Ewing sarcomas (EwS) have a poor prognosis. While inhibitory insulin-like growth factor 1 receptor (IGF-1R)-specific antibodies have shown single agent activity in some patients with refractory disease, effective therapeutic targeting will rely on optimal combinations with conventional or innovative therapies. Specifically, combination of inhibitory IGF-1R antibodies with adoptive transfer of activated natural killer (NK) cells may have therapeutic benefit in EwS without adding toxicity. PROCEDURE: We investigated the in vitro effects of IGF-1R targeting on the immunological profile of EwS cells and on the survival and tumor targeting capacity of K-562-activated NK cells. RESULTS: IGF-1R inhibition reliably reduced EwS cell viability without affecting expression of immune-modulatory and MHC molecules. In NK cells, we observed a significant superior expansion following in vitro activation in the presence of IGF-1R-specific antibodies, while expression of differentiation markers and activating receptors remained unaffected. Activated NK cells coincubated with EwS cells showed potent degranulation responses unaffected by IGF-1R inhibition. These findings were reproducible in a stimulator cell-free NK cell expansion system, suggesting that direct effects of IGF-R1 antibodies on the IGF-R1 pathway in NK cells induce their activation and expansion. CONCLUSIONS: Activated human NK cells respond to IGF-1R inhibition with superior expansion kinetics while maintaining potent antitumor responses against EwS. Combination of adoptive NK cell transfer with IGF-1R targeting may be an efficient means to eliminate minimal residual disease after conventional therapy and thereby rescue patients at the highest risk of relapse. PMID- 26131573 TI - A Second Life For Scraps: Making Biogas From Food Waste. PMID- 26131574 TI - [Tracheotomy - surgical and percutaneous]. AB - Modern indications for tracheostomy are the following: support of mechanical ventilation and weaning from mechanical ventilation, prevention of complications due to prolonged endotracheal tube ventilation. Surgical tracheostomy (ST) still plays an important role in the management of respiratory failure despite the wide use of percutaneous dilatational tracheostomy (PDT). Peri- and postoperative complication rates as well as lethality rates of these competing procedures are similar according to the literature. However, there are more contraindications to PDT to be considered. In case of technical difficulties or failure of the PDT, a conversion to the open procedure may be necessary either after PDT attempt or later on. Therefore, technical expertise should be available in the intensive care setting. Indications, technical aspects, including closure of stoma, of both methods are presented in detail. Moreover, specific complications are presented, as well as results of meta-analyses comparing ST with PDT. PMID- 26131575 TI - The effect of A163G polymorphism in the osteoprotegerin gene on osteoporosis related traits in Slovak postmenopausal women. AB - Osteoprotegerin (OPG) plays an important role in the osteoclast differentiation as an effective inhibitor of osteoclast maturation and activation. We examined a potential effect of A163G single nucleotide polymorphism in the promoter region of the OPG gene on femoral neck (FN-BMD) and lumbar spine BMD (LS-BMD), as well as circulating alkaline phosphatase, osteocalcin (ALP, OC; formation markers), beta-CrossLaps (CTx; resorption marker) in Slovak postmenopausal women. In addition, fractures of spine, radius and femur were examined.Altogether 284 women (62.28 +/- 8.40 years) were selected according to strict inclusion criteria. The polymorphism was detected by PCR-RFLP method. Genotype frequencies were tested using the chi-square test. The differences of quantitative variables between the genotypes were analyzed by covariance analysis (GLM procedure) after correction of the measurements for age and BMI. Fracture incidence in association with OPG genotype was evaluated by Binary Logistic Regression with the genotype, age, and BMI as covariates. The frequencies of genotypes were 76.8 %, 21.1 %, and 2.1 % for AA, AG, and GG, respectively. Statistically significant associations of OPG genotypes with FN-BMD (p < 0.01) and LS-BMD (p < 0.05) were observed. The GG genotype was associated with higher BMD values likewise decreased CTx concentration (p < 0.05) in compared with the other genotypes, which indicates that the allele G has a protective effect on bone. These associations were not followed by the effect of OPG on fracture incidence. Our results suggest that OPG/A163G polymorphism could contribute to the genetic regulation of BMD or bone turnover markers in Slovak population and thus could increase or decreased osteoporosis risk. PMID- 26131587 TI - SUMOylation of the C-terminal domain of DNA topoisomerase IIalpha regulates the centromeric localization of Claspin. AB - DNA topoisomerase II (TopoII) regulates DNA topology by its strand passaging reaction, which is required for genome maintenance by resolving tangled genomic DNA. In addition, TopoII contributes to the structural integrity of mitotic chromosomes and to the activation of cell cycle checkpoints in mitosis. Post translational modification of TopoII is one of the key mechanisms by which its broad functions are regulated during mitosis. SUMOylation of TopoII is conserved in eukaryotes and plays a critical role in chromosome segregation. Using Xenopus laevis egg extract, we demonstrated previously that TopoIIalpha is modified by SUMO on mitotic chromosomes and that its activity is modulated via SUMOylation of its lysine at 660. However, both biochemical and genetic analyses indicated that TopoII has multiple SUMOylation sites in addition to Lys660, and the functions of the other SUMOylation sites were not clearly determined. In this study, we identified the SUMOylation sites on the C-terminal domain (CTD) of TopoIIalpha. CTD SUMOylation did not affect TopoIIalpha activity, indicating that its function is distinct from that of Lys660 SUMOylation. We found that CTD SUMOylation promotes protein binding and that Claspin, a well-established cell cycle checkpoint mediator, is one of the SUMOylation-dependent binding proteins. Claspin harbors 2 SUMO-interacting motifs (SIMs), and its robust association to mitotic chromosomes requires both the SIMs and TopoIIalpha-CTD SUMOylation. Claspin localizes to the mitotic centromeres depending on mitotic SUMOylation, suggesting that TopoIIalpha-CTD SUMOylation regulates the centromeric localization of Claspin. Our findings provide a novel mechanistic insight regarding how TopoIIalpha-CTD SUMOylation contributes to mitotic centromere activity. PMID- 26131588 TI - RETICULAR PSEUDODRUSEN ON INFRARED IMAGING ARE TOPOGRAPHICALLY DISTINCT FROM SUBRETINAL DRUSENOID DEPOSITS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY. AB - PURPOSE: To evaluate the quantitative and topographic relationship between reticular pseudodrusen (RPD) on infrared reflectance (IR) and subretinal drusenoid deposits (SDD) on en face volumetric spectral domain optical coherence tomography. METHODS: Reticular pseudodrusen were marked on IR images by a masked observer. Subretinal drusenoid deposits were visualized on en face sections of spectral domain optical coherence tomography below the external limiting membrane and identified by a semiautomated technique. Control RPD lesions were generated in a random distribution for each IR image. Binary maps of control and experimental RPD and SDD were merged and analyzed in terms of topographic localization and quantitative drusen load comparison. RESULTS: A total of 54 eyes of 41 patients diagnosed with RPD were included in this study. The average number of RPD lesions on IR images was 320 +/- 44.62 compared with 127 +/- 26.02 SDD lesions on en face (P < 0.001). The majority of RPD lesions did not overlap with SDD lesions and were located >30 MUm away (92%). The percentage of total SDD lesions overlapping RPD was 2.91 +/- 0.87% compared with 1.73 +/- 0.68% overlapping control RPD lesions (P < 0.05). The percentage of total SDD lesions between 1 and 3 pixels of the nearest RPD lesion was 5.08 +/- 1.40% compared with 3.33 +/- 1.07% between 1 and 3 pixels of the nearest control RPD lesion (P < 0.05). CONCLUSION: This study identified significantly more RPD lesions on IR compared with SDD lesions on en face spectral domain optical coherence tomography and found that a large majority of SDD (>90% of lesions) were >30 MUm away from the nearest RPD. Together, our findings indicate that RPD and SDD are two entities that are only occasionally topographically associated, suggesting that at some stage in their development, they may be pathologically related. PMID- 26131589 TI - Reply: To PMID 25313711. PMID- 26131590 TI - DDT Vertical Migration and Formation of Accumulation Layer in Pesticide-Producing Sites. AB - Soil samples were collected at various depths (0.5-21.5 m) from ten boreholes that were drilled with a SH-30 Model Rig, four of which were at a dicofol production site while six were at a dichlorodiphenyltrichloroethane (DDT) production site. In industrial sites, the shallow soils at depths of 0-2 m were mostly backfill soils, which cannot represent the contamination situation of the sites. The contaminated levels in the deep original soil can represent the situation in contaminated sites. All the soil samples investigated at the DDT and dicofol production sites were found to be seriously polluted. The contents of both DDT (0.6-6071 mg/kg) and dicofol (0.5-1440 mg/kg) were much higher at the dicofol production site than at the DDT production site (DDTs, 0.01-664.6 mg/kg; dicofol, <0.1 mg/kg), even in the deep soil. DDTs had a different distribution in the soil of the pesticide production site from that in the soil outside the sites and that in agricultural soils. The results of the investigation revealed that DDTs were easily enriched in cohesive soil and in the bottom zone of aquifers, where the concentration was higher than in above the layers. DDTs were found to be hard to degrade, and their degradation speed was slower than their vertical migration, despite the fact that hydrophobic DDTs did not migrate easily in soils. In the dicofol production site, the value of DDE/DDD cannot indicate the degradation condition of DDTs, nor can the value of (DDE + DDD)/DDT identify how long DDTs have remained in the soil. It is debatable that the half-life of DDT inputted to soils is about 20-30 years, maybe longer than the generally recognized time. PMID- 26131591 TI - A Method for Remotely Silencing Neural Activity in Rodents During Discrete Phases of Learning. AB - This protocol describes how to temporarily and remotely silence neuronal activity in discrete brain regions while animals are engaged in learning and memory tasks. The approach combines pharmacogenetics (Designer-Receptors-Exclusively-Activated by-Designer-Drugs) with a behavioral paradigm (sensory preconditioning) that is designed to distinguish between different forms of learning. Specifically, viral mediated delivery is used to express a genetically modified inhibitory G-protein coupled receptor (the Designer Receptor) into a discrete brain region in the rodent. Three weeks later, when designer receptor expression levels are high, a pharmacological agent (the Designer Drug) is administered systemically 30 min prior to a specific behavioral session. The drug has affinity for the designer receptor and thus results in inhibition of neurons that express the designer receptor, but is otherwise biologically inert. The brain region remains silenced for 2-5 hr (depending on the dose and route of administration). Upon completion of the behavioral paradigm, brain tissue is assessed for correct placement and receptor expression. This approach is particularly useful for determining the contribution of individual brain regions to specific components of behavior and can be used across any number of behavioral paradigms. PMID- 26131592 TI - Spatial compression: Dissociable effects at the time of saccades and blinks. AB - Various studies have identified systematic errors, such as spatial compression, when observers report the locations of objects displayed around the time of saccades. Localization errors also occur when holding spatial representations in visual working memory. Such errors, however, have not been examined in the context of eye blinks. In this study, we examined the effects of blinks and saccades when observers reproduced the locations of a set of briefly presented, randomly placed discs. Performance was compared with a fixation-only condition in which observers simply held these representations in working memory for the same duration; this allowed us to elucidate the relationship between the perceptual phenomena related to blinks, saccades, and visual working memory. Our results indicate that the same amount of spatial compression is experienced prior to a blink as is experienced in the control fixation-only condition, suggesting that blinks do not increase compression above that occurring from holding a spatial representation in visual memory. Saccades, however, tend to increase these compression effects and produce translational shifts both toward and away from saccade targets (depending on the time of the saccade onset in relation to the stimulus offset). A higher numerosity recall capacity was also observed when stimuli were presented prior to a blink in comparison with the other conditions. These findings reflect key differences underlying blinks and saccades in terms of spatial compression and translational shifts. Such results suggest that separate mechanisms maintain perceptual stability across these visual events. PMID- 26131593 TI - Orientational Jumps in (Acetamide + Electrolyte) Deep Eutectics: Anion Dependence. AB - All-atom molecular dynamics simulations have been carried out to investigate orientation jumps of acetamide molecules in three different ionic deep eutectics made of acetamide (CH3CONH2) and lithium salts of bromide (Br(-)), nitrate (NO3( )) and perchlorate (ClO4(-)) at approximately 80:20 mole ratio and 303 K. Orientational jumps have been dissected into acetamide-acetamide and acetamide ion catagories. Simulated jump characteristics register a considerable dependence on the anion identity. For example, large angle jumps are relatively less frequent in the presence of NO3(-) than in the presence of the other two anions. Distribution of jump angles for rotation of acetamide molecules hydrogen bonded (H-bonded) to anions has been found to be bimodal in the presence of Br(-) and is qualitatively different from the other two cases. Estimated energy barrier for orientation jumps of these acetamide molecules (H-bonded to anions) differ by a factor of ~2 between NO3(-) and ClO4(-), the barrier height for the latter being lower and ~0.5kBT. Relative radial and angular displacements during jumps describe the sequence ClO(4)- > NO3(-) > Br(-) and follow a reverse viscosity trend. Jump barrier for acetamide-acetamide pairs reflects weak dependence on anion identity and remains closer to the magnitude (~0.7kBT) found for orientation jumps in molten acetamide. Jump time distributions exhibit a power law dependence of the type, P(tjump) ? A(tjump/tau)(-beta), with both beta and tau showing substantial anion dependence. The latter suggests the presence of dynamic heterogeneity in these systems and supports earlier conclusions from time resolved fluorescence measurements. PMID- 26131594 TI - Dissecting Ubiquitin Folding Using the Self-Organized Polymer Model. AB - Folding of Ubiquitin (Ub), a functionally important protein found in eukaryotic organisms, is investigated at low and neutral pH at different temperatures using simulations of the coarse-grained self-organized-polymer model with side chains (SOP-SC). The melting temperatures (Tm's), identified with the peaks in the heat capacity curves, decrease as pH decreases, in qualitative agreement with experiments. The calculated radius of gyration, showing dramatic variations with pH, is in excellent agreement with scattering experiments. At Tm, Ub folds in a two-state manner at low and neutral pH. Clustering analysis of the conformations sampled in equilibrium folding trajectories at Tm, with multiple transitions between the folded and unfolded states, shows a network of metastable states connecting the native and unfolded states. At low and neutral pH, Ub folds with high probability through a preferred set of conformations resulting in a pH dependent dominant folding pathway. Folding kinetics reveal that Ub assembly at low pH occurs by multiple pathways involving a combination of nucleation-collapse and diffusion collision mechanism. The mechanism by which Ub folds is dictated by the stability of the key secondary structural elements responsible for establishing long-range contacts and collapse of Ub. Nucleation collapse mechanism holds if the stability of these elements are marginal, as would be the case at elevated temperatures. If the lifetimes associated with these structured microdomains are on the order of hundreds of microseconds, then Ub folding follows the diffusion-collision mechanism with intermediates, many of which coincide with those found in equilibrium. Folding at neutral pH is a sequential process with a populated intermediate resembling that sampled at equilibrium. The transition state structures, obtained using a Pfold analysis, are homogeneous and globular with most of the secondary and tertiary structures being native-like. Many of our findings for both the thermodynamics and kinetics of folding are not only in agreement with experiments but also provide missing details not resolvable in standard experiments. The key prediction that folding mechanism varies dramatically with pH is amenable to experimental tests. PMID- 26131595 TI - Simple and Computer-assisted Olfactory Testing for Mice. AB - Olfaction is highly conserved among species and is required for reproduction and survival. In humans, olfaction is also one of the senses that is affected with aging and is a strong predictor of neurodegenerative diseases. Thus, olfaction testing is used as a non-invasive diagnostic method to detect neurological deficits early on. In order to understand the mechanisms underlying olfactory network susceptibility, olfactory research in rodents has gained momentum in the past decade. Here, we present a very simple, time efficient and reproducible olfactory testing method of innate odor perception and sensitivity in mice without the need of any prior food or water restriction. The tests are performed in a familiar environment to the mice, require only the scents and a 2 min session of odorant exposure. The analysis is performed, post-hoc, using computer assisted commands on ImageJ and can be, therefore, carried out from start to end by one researcher. This protocol does not require any special hardware or setup and is indicated for any laboratory interested in testing olfactory perception and sensitivity. PMID- 26131598 TI - Open Lung in Lateral Decubitus With Differential Selective Positive End Expiratory Pressure in an Experimental Model of Early Acute Respiratory Distress Syndrome. AB - OBJECTIVE: After lung recruitment, lateral decubitus and differential lung ventilation may enable the titration and application of optimum-selective positive end-expiratory pressure values for the dependent and nondependent lungs. We aimed at compare the effects of optimum-selective positive end-expiratory pressure with optimum global positive end-expiratory pressure on regional collapse and aeration distribution in an experimental model of acute respiratory distress syndrome. DESIGN: Prospective laboratory investigation. SETTING: University animal research laboratory. SUBJECTS: Seven piglets. INTERVENTIONS: A one-hit injury acute respiratory distress syndrome model was established by repeated lung lavages. After replacing the tracheal tube by a double-lumen one, we initiated lateral decubitus and differential ventilation. After maximum recruitment maneuver, decremental positive end-expiratory pressure titration was performed. The positive end-expiratory pressure corresponding to maximum dynamic compliance was defined globally (optimum global positive end-expiratory pressure) and for each individual lung (optimum-selective positive end-expiratory pressure). After new maximum-recruitment maneuver, two steps were performed in randomized order (15 min each): ventilation applying the optimum global positive end-expiratory pressure and the optimum-selective positive end-expiratory pressure. CT scans were acquired at end expiration and end inspiration. MEASUREMENTS AND MAIN RESULTS: Aeration homogeneity was evaluated as a nondependent/dependent ratio (percent of total gas content in upper lung/percent of total gas content in lower lung) and tidal recruitment as the difference in the percent mass of nonaerated tissue between expiration and inspiration. At the end of the 15-minute optimum-selective positive end-expiratory pressure, compared with the optimum global positive end-expiratory pressure, resulted in 1) decrease in the percent mass of collapse in the lower lung at expiratory CT (19% +/- 15% vs 4% +/- 5%; p = 0.03); 2) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-expiratory-CT and optimum selective positive end-expiratory pressure-expiratory-CT (3.7 +/- 1.2 vs 0.8 +/- 0.5; p = 0.01); 3) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-inspiratory-CT and optimum selective positive end-expiratory pressure-inspiratory-CT (2.8 +/- 1.1 vs 0.6 +/- 0.3; p = 0.01); and 4) less tidal recruitment (p = 0.049). CONCLUSIONS: After maximum lung recruitment, lateral decubitus and differential lung ventilation enabled the titration of optimum-selective positive end-expiratory pressure values for the dependent and the nondependent lungs, made possible the application of an optimized regional open lung approach, promoted better aeration distribution, and minimized lung tissue inhomogeneities. PMID- 26131597 TI - Rehospitalizations Following Sepsis: Common and Costly. AB - OBJECTIVE: Although recent studies have shown that 30-day readmissions following sepsis are common, the overall fiscal impact of these rehospitalizations and their variability between hospitals relative to other high-risk conditions, such as congestive heart failure and acute myocardial infarction, are unknown. The objectives of this study were to characterize the frequency, cost, patient-level risk factors, and hospital-level variation in 30-day readmissions following sepsis compared with congestive heart failure and acute myocardial infarction. DESIGN: A retrospective cohort analysis of hospitalizations from 2009 to 2011. SETTING: All acute care, nonfederal hospitals in California. PATIENTS: Hospitalizations for sepsis (n = 240,198), congestive heart failure (n = 193,153), and acute myocardial infarction (n = 105,684) identified by administrative discharge codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the frequency and cost of all-cause 30-day readmissions following hospitalization for sepsis compared with congestive heart failure and acute myocardial infarction. Variability in predicted readmission rates between hospitals was calculated using mixed-effects logistic regression analysis. The all-cause 30-day readmission rates were 20.4%, 23.6%, and 17.7% for sepsis, congestive heart failure, and acute myocardial infarction, respectively. The estimated annual costs of 30-day readmissions in the state of California during the study period were $500 million/yr for sepsis, $229 million/yr for congestive heart failure, and $142 million/yr for acute myocardial infarction. The risk- and reliability-adjusted readmission rates across hospitals ranged from 11.0% to 39.8% (median, 19.9%; interquartile range, 16.1-26.0%) for sepsis, 11.3% to 38.4% (median, 22.9%; interquartile range, 19.2-26.6%) for congestive heart failure, and 3.6% to 40.8% (median, 17.0%; interquartile range, 12.2-20.0%) for acute myocardial infarction. Patient-level factors associated with higher odds of 30-day readmission following sepsis included younger age, male gender, Black or Native American race, a higher burden of medical comorbidities, urban residence, and lower income. CONCLUSION: Sepsis is a leading contributor to excess healthcare costs due to hospital readmissions. Interventions at clinical and policy levels should prioritize identifying effective strategies to reduce sepsis readmissions. PMID- 26131601 TI - Higher-Affinity Agonists of 5-HT1AR Discovered through Tuning the Binding-Site Flexibility. AB - Discovery of high-affinity and high-selectivity agonists of 5-HT1AR has become very attractive due to their potential therapeutic effects on multiple 5-HT1AR related psychological and neurological problems. On the basis of our previously designed lead compound FW01 (Ki = 51.9 nM, denoted as 9a in the present study), we performed large-scale molecular dynamics simulations and molecular docking operations on 5-HT1AR-9a binding. We found the flip-packing events for the headgroup of 9a, and we also found that its tail group could bind flexibly at the agonist-binding site of 5-HT1AR. By finely tuning the flip-packing phenomenon of the 9a headgroup and tuning the binding flexibility of 9a tail group, we virtually designed a series of new 9a derivatives through molecular docking operations and first-principles calculations and predicted that these newly designed 9a derivatives should be higher-affinity agonists of 5-HT1AR. The computational predictions on the new 9a derivatives have been confirmed by our wet-experimental studies as chemical synthesis, binding affinity assays, and agonistic-function assays. The consistency between our computational design and wet-experimental measurements has led to our discovery of higher-affinity agonists of 5-HT1AR, with ~50-fold increase in receptor-binding affinity and ~25 fold improvements in agonistic function. In addition, our newly designed 5-HT1AR agonists showed very high selectivity of 5-HT1AR over subtype 5-HT2AR and also over three subtypes of dopamine receptors (D1, D2, and D3). PMID- 26131602 TI - A systematic analysis of human lipocalin family and its expression in esophageal carcinoma. AB - The lipocalin proteins (lipocalins) are a large family of small proteins characterized by low sequence similarity and highly conserved crystal structures. Lipocalins have been found to play important roles in many human diseases. For this reason, a systemic analysis of the molecular properties of human lipocalins is essential. In this study, human lipocalins were found to contain four structurally conserved regions (SCRs) and could be divided into two subgroups. A human lipocalin protein-protein interaction network (PPIN) was constructed and integrated with their expression data in esophageal carcinoma. Many lipocalins showed obvious co-expression patterns in esophageal carcinoma. Their subcellular distributions also suggested these lipocalins may transfer signals from the extracellular space to the nucleus using the pathway-like paths. These analyses also expanded our knowledge about this human ancient protein family in the background of esophageal carcinoma. PMID- 26131605 TI - Spiro Diorthoester (SpiDo), a Human Plasma Stable Acid-Sensitive Cleavable Linker for Lysosomal Release. AB - pH-sensitive linkers designed to undergo selective hydrolysis at acidic pH compared to physiological pH can be used for selective release of therapeutics selectively at targets and orthoesters have been demonstrated to be good candidates for such linkers. Following an HPLC screening, a Spiro Diorthoester (SpiDo) derivative was identified as a potent acid-labile group for the development of pH-sensitive targeted systems. After incorporation of this linker into activatable FRET-based probe and side-by-side comparison to a well-known alkylhydrazone linker, this SpiDo linker has shown a fast and pH sensitive hydrolysis for mild acidic conditions, a pH sensitive lysosomal hydrolysis, and high stability in human plasma. PMID- 26131603 TI - Immunohistochemical Subcellular Localization of Protein Biomarkers Distinguishes Benign from Malignant Thyroid Nodules: Potential for Fine-Needle Aspiration Biopsy Clinical Application. AB - BACKGROUND: It is of critical clinical importance to select accurately for surgery thyroid nodules at risk for malignancy and avoid surgery on those that are benign. Using alterations in subcellular localization for seven putative biomarker proteins (identified by proteomics), this study aimed to define a specific combination of proteins in surgical tissues that could distinguish benign from malignant nodules to assist in future surgical selection by fine needle aspiration biopsy (FNAB). METHODS: Immunohistochemical subcellular localization (IHC) analyses of seven proteins were retrospectively performed on surgical tissues (115 benign nodules and 114 papillary-based thyroid carcinomas [TC]), and a risk model biomarker panel was developed and validated. The biomarker panel efficacy was verified in 50 FNAB formalin-fixed and paraffin embedded cell blocks, and 26 cytosmears were prepared from fresh surgically resected thyroid nodules. RESULTS: Selection modeling using these proteins resulted in nuclear phosphoglycerate kinase 1 (PGK1) loss and nuclear Galectin-3 overexpression as the best combination for distinguishing TC from benign nodules (area under the curve [AUC] 0.96 and 0.95 in test and validation sets, respectively). A computed malignancy score also accurately identified TC in benign and indeterminate nodules (test and validation sets: AUC 0.94, 0.90; specificity 98%, 99%). Its efficacy was confirmed in surgical FNAB cell blocks and cytosmears. CONCLUSION: Using surgical tissues, it was observed that a combination of PGK1 and Galectin-3 had high efficiency for distinguishing benign from malignant thyroid nodules and could improve surgical selection for TC among indeterminate nodules. Further validation in prospective preoperative FNAB will be required to confirm such a clinical application. PMID- 26131606 TI - Distributed leadership in health care teams: Constellation role distribution and leadership practices. AB - BACKGROUND AND PURPOSE: Recent literature has been critical of research that adopts a narrow focus on single leaders and on leadership attributes and has called for attention to leadership that is distributed among individuals and to practices in which leaders engage. We conducted a study of health care teams where we attended to role distribution among leadership constellation members and to loose or tight coupling practices between leaders and the remainder of the team. This focus provides insights into how leadership can be practiced and structured to enhance team functioning. METHODOLOGY: A qualitative, multicase study of four teams was conducted. Data collection involved 44 interviews with almost all the members of the teams and 18 team meeting observations. Thematic analysis was conducted by the two authors. FINDINGS: Leadership constellations can give rise to leadership role overlaps and gaps that may create ambiguity within teams, ambiguity is diminished if the leaders can agree on which leader assumes ultimate authority in an area, the presence of more leaders does not necessarily entail more comprehensive fulfillment of team needs, and teams' needs for tight or loose leadership practices are influenced by contextual factors that we elaborate. PRACTICE IMPLICATIONS: (a) It is important to recognize areas of overlap and gaps in leadership roles and to provide clarity about role boundaries to avoid ambiguity. Role mapping exercises and open discussions should be considered. (b) Attempting to spread formal leadership responsibilities informally among individuals is not always a workable strategy for addressing team needs. PMID- 26131608 TI - Use of foreign-educated nurses and patient satisfaction in U.S. hospitals. AB - PURPOSE: In the context of value-based purchasing, this study examines the association between the utilization of foreign-educated registered nurses (RNs) and patient satisfaction among U.S. acute care hospitals. DATA SOURCES/STUDY SETTING: We utilized data from the Hospital Consumer Assessment of Healthcare Providers and Systems to measure patient satisfaction and data from the American Hospital Association regarding the utilization of foreign-educated RNs in 2012. METHODOLOGY/APPROACH: In this study, a cross-sectional design with propensity score adjustment to examine the relationship between use of foreign-educated nurses and 10 patient satisfaction outcome measures. Control variables include hospital size, ownership, geographic location, teaching status, system membership, a high-technology index, and U.S. region based on census categories. FINDINGS: The utilization of foreign-educated RNs was negatively and significantly related to six patient satisfaction measures. Specifically, hospitals with foreign-educated RNs scored, on average, lower on measures related to nurse communication (beta = -0.649, p = .01), doctor's communication (beta = 0.837, p <= .001), communication about administered drugs (beta = -0.539, p = .81), and communication about what to do during their recovery at home (beta = 0.571, p = .01). Moreover, hospitals utilizing foreign-educated RNs scored, on average, lower on overall satisfaction measures including rating the hospital as 9 or 10 overall (beta = -1.20, p = .005), and patients would definitely recommend the hospital (beta = -1.32, p = .006). PRACTICE IMPLICATIONS: Utilization of foreign-educated RNs is negatively associated with measures of patient satisfaction pertaining to communication and overall perceptions of care. Hospitals that utilize foreign-educated RNs should consider strategies that enhance communication competency and aid improving perception of care among patients. PMID- 26131607 TI - Achieving Kaiser Permanente quality. AB - BACKGROUND: The Kaiser Permanente model of integrated health delivery is highly regarded for high-quality and efficient health care. Efforts to reproduce Kaiser's success have mostly failed. One factor that has received little attention and that could explain Kaiser's advantage is its commitment to and investment in nursing as a key component of organizational culture and patient centered care. PURPOSE: The aim of this study was to investigate the role of Kaiser's nursing organization in promoting quality of care. METHODOLOGY: This was a cross-sectional analysis of linked secondary data from multiple sources, including a detailed survey of nurses, for 564 adult, general acute care hospitals from California, Florida, Pennsylvania, and New Jersey in 2006-2007. We used logistic regression models to examine whether patient (mortality and failure to-rescue) and nurse (burnout, job satisfaction, and intent-to-leave) outcomes in Kaiser hospitals were better than in non-Kaiser hospitals. We then assessed whether differences in nursing explained outcomes differences between Kaiser and other hospitals. Finally, we examined whether Kaiser hospitals compared favorably with hospitals known for having excellent nurse work environments-Magnet hospitals. FINDINGS: Patient and nurse outcomes in Kaiser hospitals were significantly better compared with non-Magnet hospitals. Kaiser hospitals had significantly better nurse work environments, staffing levels, and more nurses with bachelor's degrees. Differences in nursing explained a significant proportion of the Kaiser outcomes advantage. Kaiser hospital outcomes were comparable with Magnet hospitals, where better outcomes have been largely explained by differences in nursing. IMPLICATIONS: An important element in Kaiser's success is its investment in professional nursing, which may not be evident to systems seeking to achieve Kaiser's advantage. Our results suggest that a possible strategy for achieving outcomes like Kaiser may be for hospitals to consider Magnet designation, a proven and cost-effective strategy to improve process of care through investments in nursing. PMID- 26131609 TI - The influence of organization tenure on nurses' perceptions of multiple work process improvement initiatives. AB - BACKGROUND: A nurse's optimism or skepticism toward an organization-mandated change initiative largely depends on their experience with similar change initiatives and their unit's and organization's track record with previous change efforts. Thus, depending on the context, organization tenure can work in favor or against any particular change initiative. However, few studies have examined the impact of organization tenure on perceptions toward change initiatives. The few studies that have been conducted have yielded mixed results and have only targeted single or similar work initiatives. PURPOSE: The aim of this study was to examine how organization tenure impacts nurses' perceptions toward a diverse array of work process improvement initiatives. METHODOLOGY: The data are derived from a survey of 421 medical-surgical nurses representing 41 units across four hospitals. The survey was designed to capture nurses' perceptions toward three change initiatives-AIDET (Acknowledge, Introduce, Duration, Explanation, and Thank You), hourly rounding, and discharge phone calls-and their impact across two subscales-patient care and individual work change. FINDINGS: Organization tenure is significantly and negatively associated with change receptivity for the non-patient safety-oriented initiative (AIDET). This negative relationship dissipates as we evaluate more patient safety-oriented work process initiatives (hourly rounding and discharge phone calls). PRACTICE IMPLICATIONS: Significant differences in nurses' perceptions toward change do exist depending on how long they have worked for their employer. For non-patient safety-oriented change initiatives, veteran-to-the-organization nurses may exhibit more recalcitrance than their new-to-the-organization counterparts. However, our findings also suggest the presence of a patient safety exception rule where veteran-to-the organization nurses do not exhibit differences in opinion than their new-to-the organization counterparts for patient safety-oriented change initiatives. PMID- 26131610 TI - Sensitization at the first wheezing episode increases risk for long-term asthma therapy. PMID- 26131611 TI - Barriers and enablers of James Cook University Bachelor of Medicine, Bachelor of Surgery graduates pursuing a research career. AB - OBJECTIVE: The period 2000-2011 has seen a decline in medical graduates participating in research. However, significant change has taken place in recent years at the James Cook University (JCU), with a sharp increase in medical graduates enrolling in the Honours course. Our study aims to explore the involvement of JCU medical graduates in research, including 'barriers' and 'enablers' of this involvement. DESIGN: Cross-sectional questionnaire to the first six cohorts of JCU medical graduates. SETTING: Survey distributed online via SurveyMonkey to graduates who had previously consented to be contacted for future studies. PARTICIPANTS: Three hundred thirty-eight early-career doctors from PGY (postgraduate year) 4 to PGY9 (n = 185, response rate = 55%). MAIN OUTCOME MEASURES: Current research participation. RESULTS: Fifty-six (30%) of the responding 185 JCU medical graduates were currently undertaking research. Graduates who completed an Honours degree by research (P = 0.001) and students who received some form of research training and mentoring during their undergraduate studies(P = 0.024) were statistically more likely to be currently involved in research. Vocational training requirements were both a significant barrier and enabler to research participation. CONCLUSIONS: Participation in the Honours program and receiving training and mentoring during undergraduate studies predict future research involvement by JCU medical graduates. However, many postgraduate barriers for involvement in research exist. This study highlights potential areas for improving medical graduate involvement in research, including medical schools promoting student research training and mentoring in their curriculum, and specialty colleges incorporating a research component in their selection or training requirements. PMID- 26131612 TI - Efficacy of Liuzijue Qigong in Individuals with Chronic Obstructive Pulmonary Disease in Remission. AB - OBJECTIVES: To investigate the effectiveness of a 6-month Liuzijue qigong (LQG) program in promoting physical and psychosocial function in individuals with chronic obstructive pulmonary disease (COPD). DESIGN: Single-blind, randomized controlled trial. SETTING: Seven hospital respiratory care centers in Beijing. PARTICIPANTS: Individuals with COPD (N = 126; mean age 71.1 +/- 2.7, range 65 85). METHODS: Participants were randomly assigned to one of two groups: LQG (n = 63) and control (n = 63). Subjects in the LQG group received a LQG program consisting of four 45-minute sessions each week and daily walking for 30 minutes for 6 months. Control subjects walked daily for 30 minutes. Data collection was performed at baseline, at 6 weeks, and at 6 months. Primary outcomes involved functional capacity, and secondary outcomes involved quality of life. RESULTS: The LQG group had greater improvements in the 6-minute walk test (P = .02); specific airway conductance (P = .02); monitored functional task evaluation (P = .04); Medical Outcomes Study 36-item Short-Form Health Survey (SF-36; general health (P < .001), mental health (P = .03)); Chronic Respiratory Questionnaire (dyspnea (P = .05), emotion (P = .05), and mastery (P = .04) at 6-month follow up. After 6 months, the control group had significant improvement only on the SF 36 mental health (P = .02). CONCLUSION: LQG promoted functional capacity and quality of life in older adults with COPD at 6 months and is a good alternative home exercise program for older adults in the rehabilitation of COPD. PMID- 26131613 TI - Molecular Characterization of the Multidrug Resistant Escherichia coli ST131 Clone. AB - Escherichia coli ST131 is a recently emerged and globally disseminated multidrug resistant clone associated with urinary tract and bloodstream infections in both community and clinical settings. The most common group of ST131 strains are defined by resistance to fluoroquinolones and possession of the type 1 fimbriae fimH30 allele. Here we provide an update on our recent work describing the globally epidemiology of ST131. We review the phylogeny of ST131 based on whole genome sequence data and highlight the important role of recombination in the evolution of this clonal lineage. We also summarize our findings on the virulence of the ST131 reference strain EC958, and highlight the use of transposon directed insertion-site sequencing to define genes associated with serum resistance and essential features of its large antibiotic resistance plasmid pEC958. PMID- 26131614 TI - Fasciola hepatica: Histology of the Reproductive Organs and Differential Effects of Triclabendazole on Drug-Sensitive and Drug-Resistant Fluke Isolates and on Flukes from Selected Field Cases. AB - This review summarises the findings of a series of studies in which the histological changes, induced in the reproductive system of Fasciola hepatica following treatment of the ovine host with the anthelmintic triclabendazole (TCBZ), were examined. A detailed description of the normal macroscopic arrangement and histological features of the testes, ovary, vitelline tissue, Mehlis' gland and uterus is provided to aid recognition of the drug-induced lesions, and to provide a basic model to inform similar toxicological studies on F. hepatica in the future. The production of spermatozoa and egg components represents the main energy consuming activity of the adult fluke. Thus the reproductive organs, with their high turnover of cells and secretory products, are uniquely sensitive to metabolic inhibition and sub-cellular disorganisation induced by extraneous toxic compounds. The flukes chosen for study were derived from TCBZ-sensitive (TCBZ-S) and TCBZ-resistant (TCBZ-R) isolates, the status of which had previously been proven in controlled clinical trials. For comparison, flukes collected from flocks where TCBZ resistance had been diagnosed by coprological methods, and from a dairy farm with no history of TCBZ use, were also examined. The macroscopic arrangement of the reproductive system in flukes was studied using catechol/carmine stained whole mounts, and the histology of the main organs was examined using conventional haematoxylin-eosin stained sections. Validation of apoptosis in the fluke sections was carried out using an in situ hybridisation method designed to label endonuclease-induced DNA strand breaks. In TCBZ-S flukes exposed to TCBZ metabolites for 24-96 h in vivo, but not in TCBZ-R flukes, those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), were found to display progressive loss of cell content. This was due to apparent failure of cell division to keep pace with expulsion of the mature or effete products. Further, actively dividing cell types tended to become individualised, rounded and condensed, characteristic of apoptotic cell death. In the treated TCBZ-S flukes, strong positive labelling indicating apoptosis was associated with the morphologically abnormal cells undergoing mitosis or meiosis in the testis, ovary and vitelline follicles. In treated flukes from field outbreaks of suspected TCBZ-R fasciolosis, no significant histological changes were observed, nor was there any positive labelling for apotosis. On the other hand, sections of TCBZ treated flukes derived from a field case of fasciolosis where TCBZ resistance was not suspected displayed severe histological lesions, and heavy positive labelling for apoptosis. The triggering of apoptosis is considered to be related to failure of spindle formation at cell division, supporting the contention that TCBZ inhibits microtubule formation. In treated TCBZ-S flukes, protein synthesis and transport was apparently inhibited in the Mehlis' secretory cells, perhaps due to energy uncoupling or to microtubule defects. In the uterus, successful formation of shelled eggs represents the culmination of a complex sequence of cytokinetic, cytological and synthetic activity involving the vitelline follicles, the ovary and the Mehlis' gland. Histological evidence indicating failure of ovigenesis in TCBZ-S flukes was evident from as early as 24 h post-treatment onwards. Light labelling for apoptosis was associated with the testis of untreated Cullompton (TCBZ-S) and Sligo type 2 (TCBZ-R) flukes, which exhibit abnormal spermatogenesis and spermiogenesis, respectively. This was attributed to apoptosis and to heterophagy of effete germ line cells by the sustentacular tissue. The studies summarised in this review illustrate the potential utility of histological techniques for conveniently screening representative samples of flukes in field trials designed to validate instances of drug resistance. Histology can also be used to test the efficacy of new products against known drug-resistant and drug susceptible fluke isolates. The account also provides reference criteria for drug induced histopathological changes in fluke reproductive structures, examination of which may supplement and augment conventional coprological testing, and aid interpretation of TEM findings. PMID- 26131615 TI - Elimination of Bloodstream Infections Associated with Candida albicans Biofilm in Intravascular Catheters. AB - Intravascular catheters are among the most commonly inserted medical devices and they are known to cause a large number of catheter related bloodstream infections (BSIs). Biofilms are associated with many chronic infections due to the aggregation of microorganisms. One of these organisms is the fungus Candida albicans. It has shown to be one of the leading causes of catheter-related BSIs. The presence of biofilm on intravascular catheters provide increased tolerance against antimicrobial treatments, thus alternative treatment strategies are sought. Traditionally, many strategies, such as application of combined antimicrobials, addition of antifungals, and removal of catheters, have been practiced, but they were not successful in eradicating BSIs. Since these fungal infections can result in significant morbidity, mortality, and increased healthcare cost, other promising preventive strategies, including antimicrobial lock therapy, chelating agents, alcohol, and biofilm disruptors, have been applied. In this review, current success and failure of these new approaches, and a comparison with the previous strategies are discussed in order to understand which preventative treatment is the most effective in controlling the catheter related BSIs. PMID- 26131616 TI - Energy Availability and Dietary Patterns of Adult Male and Female Competitive Cyclists With Lower Than Expected Bone Mineral Density. AB - The purpose of this study was to assess energy availability (EA) and dietary patterns of 10 adult (29-49 years) male (n = 6) and female (n = 4) competitive (USA Cycling Category: Pro, n = 2; 1-4, n = 8) endurance cyclists (5 road, 5 off road), with lower than expected bone mineral density (BMD; Z score < 0) across a season. Energy intake (EI) and exercise energy expenditure during preseason (PS), competition (C), and off-season (OS) were estimated from 3-day dietary records, completed once per month, across a cycling season. BMD was measured by DXA at 0 months/5 months/10 months. The Three-Factor Eating Questionnaire (TFEQ) was used to assess cognitive dietary restraint. Seventy percent of participants had low EA [(LEA); < 30 kcal . kg fat-free mass (FFM) (-1) . day(-1)] during PS, 90% during C, and 80% during OS (range: 3-37 kcal . kg FFM(-1) . day(-1)). Ninety percent of cyclists had LEA during >= 1 training period, and 70% had LEA across the season. Seventy percent of cyclists were identified as restrained eaters who consciously restrict EI as a means of weight control. Mean daily carbohydrate intake was below sport nutrition recommendations during each training period (PS: 3.9 +/- 1.1 g . kg(-1) . day(-1), p < .001; C: 4.3 +/- 1.4 g . kg(-1) . day(-1), p = .005; OS: 3.7 +/- 1.4 g . kg(-1) . day(-1), p = .01). There were no differences in EA and EI . kg(-1) between male and female cyclists and road and off-road cyclists. Low EI, and specifically low carbohydrate intake, appears to be the main contributor to chronic LEA in these cyclists. Adult male and female competitive road and off-road cyclists in the United States may be at risk for long-term LEA. Further studies are needed to explore strategies to prevent and monitor long-term LEA in these athletes. PMID- 26131617 TI - Evaluation of Cortical Thickness after Traumatic Brain Injury in Military Veterans. AB - Military service members frequently sustain traumatic brain injuries (TBI) while on active duty, a majority of which are related to explosive blasts and are mild in severity. Studies evaluating the cortical gray matter in persons with injuries of this nature remain scarce. The purpose of this study was to assess cortical thickness in a sample of military veterans with chronic blast-related TBI. Thirty eight veterans with mild TBI and 17 veterans with moderate TBI were compared with 58 demographically matched healthy civilians. All veterans with TBI sustained injuries related to a blast and were between 5 and 120 months post-injury (M = 62.08). Measures of post-traumatic stress disorder (PTSD) and depression were administered, along with a battery of neuropsychological tests to assess cognition. The Freesurfer software package was used to calculate cortical thickness of the participants. Results demonstrated significant clusters of cortical thinning in the right hemispheric insula and inferior portions of the temporal and frontal lobe in both mild and moderate TBI participants. The TBI sample from this study demonstrated a high incidence of comorbid PTSD and depression symptoms, which is consistent with the previous literature. Cortical thickness values correlated with measures of PTSD, depression, and post concussive symptoms. This study provides evidence of cortical thinning in the context of chronic blast-related mild and moderate TBI in military veterans who have comorbid psychiatric symptoms. Our findings provide important insight into the natural progression of long-term cortical change in this population and may have implications for future clinical evaluation and treatment. PMID- 26131618 TI - The Transformation of the Value of Life: Dispossession as Torture. AB - Workers at the oldest maternity hospital in Colombia experienced the privatization of health care and the flexibilization of their labor. Drawing on their experience, I illustrate how neoliberalism transforms the value of life. This transformation occurs first in terms of its moral worth: the worth of life changes over time, as people and public hospitals are stigmatized as the 'living memory' of the old. Second, the hospital buildings, the land on which they sit, and the roles of workers within the hospital are all transformed. Both similarities and differences emerge between a type of systemic or chronic violence that is inherent to the capitalist system and modern practices of torture. Examining how capitalist forces transform the value of life opens up new fields of inquiry to study links between critical political economy and subjectivity. PMID- 26131619 TI - Nucleotide Sugar Pucker Preference Mitigates Excision by HIV-1 RT. AB - A series of DNA primers containing nucleotides with various sugar pucker conformations at the 3'-terminus were chemically synthesized by solid-phase synthesis. The ability of wild-type (WT) HIV-1 reverse transcriptase (RT) and AZT resistant (AZTr) RT to excise the 3'-terminal nucleotide was assessed. Nucleosides with a preference for the North conformation were more refractory to excision by both WT-RT and AZTr-RT. We found that DNA primers that contain North puckered-nucleotides at the 3'-terminus can also affect the translocation status of the RT/template/primer complex, which provides an underlying mechanism to avoid being excised. Together, these results point to a correlation between the sugar conformation of the 3'-terminal nucleotide, the precise position of HIV-1 RT on its nucleic acid substrate, and, in turn, its catalytic function. Nucleotide sugar conformation is therefore an important parameter in defining the susceptibility to RT-catalyzed phosphorolytic excision. PMID- 26131620 TI - Influence of receptor flexibility on intramolecular H-bonding interactions. AB - Atropisomers of a series of zinc tetraphenyl porphyrins were synthesized and used as supramolecular receptors. Rotation around the porphyrin-meso phenyl bonds is restricted by installing ortho-chlorine substituents on the phenyl groups. The chlorine substituents allowed chromatographic separation of atropisomers, which did not interconvert at room temperature. The porphyrin meso phenyl groups were also equipped with phenol groups, which led to the formation of intramolecular H bonds when the zinc porphyrins were bound to pyridine ligands equipped with ester or amide side arms. Binding of the pyridine ligands with the conformationally locked chloroporphyrins was compared with the corresponding unsubstituted porphyrins, which are more flexible. The association constants of 150 zinc porphyrin-pyridine complexes were measured in two different solvents, toluene and 1,1,2,2-tetrachloroethane (TCE). These association constants were then used to construct 120 chemical double mutant cycles to quantify the influence of chlorine substitution on the free energy of intramolecular H-bonds formed between the phenol side arms of the porphyrins and the ester or amide side arms of the pyridine ligands. Conformational restriction leads to increases in the stability of some complexes and decreases in the stability of others with variations in the free energy contribution due to intramolecular H-bonding of -5 to +6 kJ mol(-1). PMID- 26131621 TI - Synthesis and characterization of bis(imino)pyridine complexes of divalent Mg and Zn. AB - Phenyl-bis(imino)pyridine (PhI2P) complexes, (PhI2P)ZnCl2 (1), (PhI2P-)ZnCl (2) and (PhI2P-)Zn(py)Cl (3) were obtained with the I2P ligand in both the neutral and the one-electron reduced state. In all examples, the metal ion is Zn(II). Metrical parameters obtained from solid state structures of 2 and 3 indicate that the PhI2P- ligand exists as a radical which is supported at the carbon atom of the imino donor, and this electronic state is also apparent in the analogous one electron reduced ligand Al(III) complex, (PhI2P-)AlCl2 (4), that we prepared for comparison. We were unable to obtain PhI2P Mg complexes, and so the more electron rich methyl-substituted bis(imino)pyridine ligand, MeI2P, was investigated. Reaction of two-electron reduced MeI2P with MgCl2 and Mg(OTf)2 did afford the two electron reduced ligand complexes [(MeI2P2-)Mg(THF)]2(MU-MgCl2) (5) and (MeI2P2 )Mg(THF)2 (6), respectively (MeI2P = 2,6-bis(1-methylethyl)-N-(2 pyridinylmethylene)phenylamine). Complex 5 crystallizes as a trinuclear Mg complex consisting of two (MeI2P2-)Mg moieties bridged by MgCl2 and the (MeI2P2-) ligand is symmetric across the pyridine ring, but is not planar. In contrast, the (MeI2P2-) ligand in 6 is asymmetric across the pyridine ring and all atoms in the ligand are coplanar. Cyclic voltammetry measurements reveal that in complexes, 1, 4, 5, 6, the I2P0, I2P-, and I2P2- ligand charge states are accessible electrochemically. PMID- 26131622 TI - Evaluation of Antipsychotic Dose Reduction in Late-Life Schizophrenia: A Prospective Dopamine D2/3 Receptor Occupancy Study. AB - IMPORTANCE: Patients with late-life schizophrenia (LLS) are highly susceptible to antipsychotic adverse effects. Treatment guidelines endorse lower antipsychotic doses. However, the optimal dose of antipsychotics and associated dopamine D2/3 receptor (D2/3R) occupancies remain largely unexplored in patients with LLS. OBJECTIVE: To evaluate effects of antipsychotic dose reduction on striatal dopamine D2/3R occupancies, clinical variables, and blood pharmacokinetic measures in patients with LLS. DESIGN, SETTING, AND PARTICIPANTS: An open-label, single-arm prospective study with a 3- to 6-month follow-up period (January 10, 2007, to October 21, 2013) was conducted at an academic tertiary care center with practice for ambulatory care. Participants included 35 outpatients with clinically stable LLS (patients aged >= 50 years receiving olanzapine or risperidone monotherapy at the same dose for 6 to 12 months). Follow-up was completed on October 21, 2013, and analysis was conducted from October 22, 2014, to February 2, 2015. INTERVENTIONS: Carbon 11-labeled raclopride positron emission tomography, clinical measures, and blood pharmacokinetic measures performed before and after gradual dose reduction by up to 40% from the baseline dose and at least 3 months after dose reduction. MAIN OUTCOMES AND MEASURES: Striatal dopamine D2/3R occupancies with antipsychotics, clinical measures (Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Targeted Inventory on Problems in Schizophrenia, Simpson-Angus Scale, Barnes Rating Scale for Drug-Induced Akathisia, Udvalg for Kliniske Undersogelser Side Effect Rating Scale), and blood pharmacokinetic measures (prolactin and antipsychotic blood levels). RESULTS: Dopamine D2/3R occupancy of the entire sample decreased by a mean (SD) of 6.2% (8.2%) following dose reduction (from 70% [12%] to 64% [12%]; P < .001). The lowest D2/3R occupancy associated with clinical stability was 50%. Extrapyramidal symptoms (EPSs) were more likely to occur with D2/3R occupancies higher than 60%: 90.5% (19 of 21) of the participants with baseline EPSs and 76.9% (10 of 13) of the participants with postreduction EPSs had striatal D2/3R occupancies higher than 60%. The baseline D2/3R occupancies were lower in patients with clinical deterioration (n = 5) than in those whose condition remained stable (n = 29) (58% [15%] vs 72% [10%]; P = .03). Following dose reduction, Targeted Inventory on Problems in Schizophrenia score increased (P = .046) and Positive and Negative Syndrome Scale (P = .02), Brief Psychiatric Rating Scale (P = .03), Simpson-Angus Scale (P < .001), Barnes Rating Scale for Drug-Induced Akathisia (P = .03), and Udvalg for Kliniske Undersogelser Side Effect Rating Scale (P < .001) scores and prolactin (P < .001) and blood antipsychotic (olanzapine, P < .001; risperidone plus the metabolite 9 hydroxyrisperidone, P = .02) levels all decreased. CONCLUSIONS AND RELEVANCE: Antipsychotic dose reduction is feasible in patients with stable LLS, decreasing adverse effects and improving illness severity measures. The results of the present study suggest a lower therapeutic window of D2/3R occupancy in patients with LLS (50%-60%) than previously reported in younger patients (65%-80%). PMID- 26131623 TI - Characterization of a cypermethrin-degrading Methylobacterium sp. strain A-1 and molecular cloning of its carboxylesterase gene. AB - A novel mesophilic bacterial strain, designated A-1, was isolated from microbially contaminated biopolymer microcapsules. The bacterium was able to withstand and grow in liquid cultures supplemented with the pyrethroid cypermethrin in concentrations up to 400 mg L(-1) . Furthermore, strain A-1 could use cypermethrin as sole carbon source and could degrade >50% of it in 12 h. Based on phenotypic and chemotaxonomic characterization, and phylogenetic analysis of 16S rRNA gene sequence, the strain A-1 was identified as Methylobacterium sp., which is the first reported cypermethrin degrader of methylotrophic bacteria. A role for esterase activity in cypermethrin biodegradation was presumed. Therefore, the carboxylesterase gene mse1 was amplified from the Methylobacterium sp. strain A-1 genome and the resulting 1 kb amplicon cloned into E. coli. Sequence analysis of the mse1-DNA insert revealed an open reading frame of 633 bp encoding for a putative carboxylesterase of 210 amino acid residues with a predicted molecular mass of 22 kDa. The amino acid sequence of the deduced enzyme MsE1 with the catalytic triad Ser106 , Asp156 , and His187 was found to be similar to that of alpha/beta-hydrolase fold proteins. The active site Ser106 residue is located in the consensus pentapeptide motif Gly X-Ser-X-Gly that is typical of esterases. PMID- 26131624 TI - HeLa Based Cell Free Expression Systems for Expression of Plasmodium Rhoptry Proteins. AB - Malaria causes significant global morbidity and mortality. No routine vaccine is currently available. One of the major reasons for lack of a vaccine is the challenge of identifying suitable vaccine candidates. Malarial proteins expressed using prokaryotic and eukaryotic cell based expression systems are poorly glycosylated, generally insoluble and undergo improper folding leading to reduced immunogenicity. The wheat germ, rabbit reticulocyte lysate and Escherichia coli lysate cell free expression systems are currently used for expression of malarial proteins. However, the length of expression time and improper glycosylation of proteins still remains a challenge. We demonstrate expression of Plasmodium proteins in vitro using HeLa based cell free expression systems, termed "in vitro human cell free expression systems". The 2 HeLa based cell free expression systems transcribe mRNA in 75 min and 3 ul of transcribed mRNA is sufficient to translate proteins in 90 min. The 1-step expression system is a transcription and translation coupled expression system; the transcription and co-translation occurs in 3 hr. The process can also be extended for 6 hr by providing additional energy. In the 2-step expression system, mRNA is first transcribed and then added to the translation mix for protein expression. We describe how to express malaria proteins; a hydrophobic PF3D7_0114100 Maurer's Cleft - 2 transmembrane (PfMC-2TM) protein, a hydrophilic PF3D7_0925900 protein and an armadillo repeats containing protein PF3D7_1361800, using the HeLa based cell free expression system. The proteins are expressed in micro volumes employing 2-step and 1-step expression strategies. An affinity purification method to purify 25 ul of proteins expressed using the in vitro human cell free expression system is also described. Protein yield is determined by Bradford's assay and the expressed and purified proteins can be confirmed by western blotting analysis. Expressed recombinant proteins can be used for immunizations, immunoassays and protein sequencing. PMID- 26131625 TI - Increased Minimum Mortality Temperature in France: Data Suggest Humans Are Adapting to Climate Change. PMID- 26131626 TI - Protocols for Obtaining Zygotic and Somatic Embryos for Studying the Regulation of Early Embryo Development in the Model Legume Medicago truncatula. AB - Early embryogenesis starting from a single cell zygote goes through rapid cell division and morphogenesis, and is morphologically characterized by pre-globular, globular, heart, torpedo and cotyledon stages. This progressive development is under the tight regulation of a complex molecular network. Harvesting sufficient early embryos at a similar stage of development is essential for investigating the cellular and molecular regulation of early embryogenesis. This is not straightforward since early embryogenesis undergoes rapid morphogenesis in a short while e.g. 8 days for Medicago truncatula to reach the early cotyledon stage. Here, we address the issue by two approaches. The first one establishes a linkage between embryo development and pod morphology in helping indicate the stage of the zygotic embryo. This is particularly based on the number of pod spirals and development of the spines. An alternative way to complement the in vivo studies is via culturing leaf explants to produce somatic embryos. The medium includes an unusual hormone combination - an auxin (1-naphthaleneacetic acid), a cytokinin (6-benzylaminopurine), abscisic acid and gibberellic acid. The different stages can be discerned growing out of the callus without dissection. PMID- 26131627 TI - Scientific Integrity, Precambrian Acritarchs from Brazil and Mangroves and Climate Change. PMID- 26131628 TI - Parameter induction in continuous univariate distributions: Well-established G families. AB - The art of parameter(s) induction to the baseline distribution has received a great deal of attention in recent years. The induction of one or more additional shape parameter(s) to the baseline distribution makes the distribution more flexible especially for studying the tail properties. This parameter(s) induction also proved helpful in improving the goodness-of-fit of the proposed generalized family of distributions. There exist many generalized (or generated) G families of continuous univariate distributions since 1985. In this paper, the well established and widely-accepted G families of distributions like the exponentiated family, Marshall-Olkin extended family, beta-generated family, McDonald-generalized family, Kumaraswamy-generalized family and exponentiated generalized family are discussed. We provide lists of contributed literature on these well-established G families of distributions. Some extended forms of the Marshall-Olkin extended family and Kumaraswamy-generalized family of distributions are proposed. PMID- 26131629 TI - Energy trends and the water-energy binomium for Brazil. AB - According to the demands of energy saving and carbon emission reduction, the water vs. energy nexus has become a major concern worldwide. Brazil occupies a singular position in the global energy system. A major portion of the Brazilian occupancies has electricity and the energy system expansion that, at first, possesses adequate means for supporting the economic growing may experience some turnovers. The Brazil determination through alternative fuels was a natural choice, given its large hydropower potential and land agricultural base. In the transportation sector Brazil has developed its energy matrix towards an important rate of ethanol and biodiesel. Although those fuels are low carbon emitter, they may probably not be an affordable alternative regarding land use, food security and water footprint. In this way, considering the recent advances in the exploration of oil from Pre-salt (9-15 million barrels) and the discovery of shale gas wells up to 245 tcf, together to unfavorable social and environmental issues associated to biofuels, the Brazilian energy matrix might turn back to the fossil fuels again. These represent challenges to the Brazilian policymakers and how they will be solved will reflect not only in Brazil but also to the world at large. PMID- 26131630 TI - Acritarchs of the Ediacaran Frecheirinha Formation, Ubajara Group, Northeastern Brazil. AB - We report for the first time the occurrence of organic-walled microfossils in Ediacaran limestones and marls of the Frecheirinha Formation, Ubajara Group, and the first Precambrian acritarchs so far reported for northeastern Brazil. The assemblage of the Frecheirinha Formation represents a low-diversity microflora comprising Leiosphaeridia, Lophosphaeridium and subordinated Bavlinella (=Sphaerocongregus). Their thermal alteration index (TAI) between 4+ and 5, suggests metamorphic temperatures exceeding 200-250 degrees C. Higher temperatures are probably related to intruding granitic plutons (Meruoca, Mucambo). Reported delta13C values of carbonates of -3.5 0/00 VPDB (Vienna-Peedee Belemnite) at the base, passing up section into a positive plateau of up to +3.7 0/00, and corresponding 87Sr/86Sr values between 0.7075 and 0.7080 suggest an Ediacaran age. The acritarch assemblage is comparable to the Late Ediacaran Leiosphere Palynoflora (LELP) or Kotlin-Rovno assemblage, in broad agreement with chemostratigraphic data. Macrofossils belonging to the Ediacara fauna were reported from the overlying Jaibaras Group, which would constrain even further the depositional age of the Frecheirinha Formation to within ca. 575-555 Ma. A more comprehensive palynological study of the Frecheirinha Formation is necessary to confirm this age assignment. PMID- 26131631 TI - Comments on Triassic pterosaurs with discussion about ontogeny and description of new taxa. AB - Eudimorphodon ranzii was the first Triassic pterosaur to be described and several specimens have been referred to this taxon mainly based on the presence of multicuspid teeth. Since this dental feature has been observed in several other pterosaurs, the revision of some specimens assigned to Eudimorphodon shows that they represent new taxa as follows: Arcticodactylus cromptonellus (comb. nov.), Austriadraco dallavecchiai (gen. et sp. nov.) and Bergamodactylus wildi (gen. et sp. nov.). A preliminary analysis of pterosaur ontogeny resulted in the recognition of six distinct ontogenetic stages (OS1-6). According to this classification, the holotype of Arcticodactylus cromptonellus has reached OS2, and although being ontogenetically much younger than others, the conspicuous anatomical differences lead to its exclusion from Eudimorphodon. The holotypes of Austriadraco dallavecchiai, Bergamodactylus wildi and Carniadactylus rosenfeldi have reached at least OS5, which demonstrates that the anatomical differences among them cannot be explained by ontogeny. Moreover, Bergamodactylus wildi reaches about 60% of the maximized wingspan of Carniadactylus rosenfeldi and further concurs that these specimens collected in distinct Triassic Islands of Europe are not conspecific. The present study increases the diversity of Triassic flying reptiles and further pushes the origins of this clade back to at least the Middle Triassic. PMID- 26131632 TI - Extracting DNA of nematodes communities from Argentine Pampas agricultural soils. AB - We examined four strategies (Tris/EDTA, sodium dodecyl sulfate, Chelex 100 resin and cetyltrimethylammonium bromide -CTAB-) for extracting nucleic acid (DNA) from communities of nematodes. Nematodes were isolated from an agricultural area under different management of long-term crop rotation experiment from Argentina during three seasons. After DNA extraction, Polymerase Chain Reaction-amplifications were performed and considered as indicators of successful DNA extraction. The CTAB combined with proteinase K and phenol-chloroform-isoamyl alcohol was the unique successful method because positive amplifications were obtained by using both eukaryotic and nematode specific primers. This work could contribute to biodiversity studies of nematodes on agroecosystems. PMID- 26131633 TI - Chemical compositions and termiticidal activities of the heartwood from Calophyllum inophyllum L. AB - Wood extractives from heartwood of Callophylum inophyllum (bintangor) were obtained by shaker method and analyzed for their constituents by gas chromatography-mass spectrometry (GC-MS). Ten compounds were identified by ethanol (EtOH) solvents, fourteen by methanol (MeOH) and only nine by petroleum ether (PETETHR). Major compounds were contributed by monoterpenes (75.11%, 53.75%) when extracted with EtOH and PETETHR solvents. The anti-termitic assay of the wood extracts was also investigated against Coptotermes curvignathus. The level of concentration for anti-termite activity may be an indication of the dose application of the wood extracts for new development of termiticide. PMID- 26131634 TI - Genetic and chemical diversity in seeds of cactus mandacaru (Cereus sp.) from two edaphoclimatic regions contrasting. AB - The purpose of this study was to evaluate the chemical, physiological and genetic differences in seeds of cactus of the Cereus genus (mandacaru) cultivated in the Northeast (Picos, State of Piaui) and Southern (Maringa, State of Parana) regions of Brazil. Over a period of eight days, temperatures of 25 degrees C and 30 degrees C were equally efficient for the germination of all the seeds. Oleic acid (C18:1) was the most common fatty acid found in the seeds collected in the Southern (41%) and Northeast (45.5%) regions. The analysis of lipases indicated that seeds from Maringa have high mean observed and expected heterozygosities and that seeds from Picos have a higher number of alleles per loci. Therefore, the seeds of mandacaru from the semiarid region of Northeast as well as the seeds from the South (the two contrasting regions of Brazil) are promising with regards to the preservation of the biodiversity in the genome of mandacaru. The low genetic identity between mandacaru seeds from Maringa and Picos at Lipase-5 locus analysis (I = 0.77) suggests that the mandacaru plants from Maringa and Picos may correspond to two species: C. peruvianus and C. jamacaru, respectively. PMID- 26131635 TI - Halophila baillonis Ascherson: first population dynamics data for the Southern Hemisphere. AB - The present paper presents the first population data for the Southern Hemisphere of the rare seagrass Halophila baillonis. The population studied is located in a calm, reef-protected area at depths <= 5 m, covering 12,000 m2 (400 m long by 30 m wide, oriented parallel to the coastline). The population generally demonstrated low shoot density and biomass during the rainy season, with significant differences between seasons, being found only for aboveground biomass. Despite the identification of this new population, the species continues to be considered rare along the Brazilian coast. PMID- 26131636 TI - Morphological characteristics of the digestive tract of Schizodon knerii (Steindachner, 1875), (Characiformes: Anostomidae): An anatomical, histological and histochemical study. AB - The digestive tracts of 44 specimens of Schizodon knerii were studied using anatomical, histological and histochemical techniques. The mouth has terminal position, the lip epithelium is squamous stratified with mucous, claviform cells and taste buds, teeth have an incisive form and the tongue has a stratified squamous epithelium with mucous cells and taste buds. The oropharynx cavity is formed by gill apparatus and pharyngeal teeth. The oesophagus presented pleated mucosa, a stratified squamous epithelium with mucous cells, oesophageal glands and taste buds. The stomach presented cardiac, fundic and pyloric regions, simple prismatic epithelium with tubular glands, with none in the pyloric region. The intestine contains 11-15 pyloric caeca, a simple prismatic epithelium with brush border, goblet cells and lymphocytes. Mucosal cells, oesophageal glands and goblet cells reacted positively to PAS, amylase + PAS, Ab pH 2.5 and Ab pH 0.5. Gastric prismatic cells reacted positively to PAS, amylase + PAS, but only those in the pyloric region reacted positively to Ab pH 2.5 and Ab pH 0.5. The results improve the understanding of the anatomy of S. knerii feeding habits and the presence of mucosubstances in the epithelium, highlights the importance of glycoproteins for passing food through the digestive tract. PMID- 26131637 TI - A new Amphisbaena (Squamata: Amphisbaenidae) from southern Espinhaco Range, southeastern Brazil. AB - A new species of Amphisbaena is described from a semi-deciduous forest in Conceicao do Mato Dentro, southern Espinhaco Range, Minas Gerais, Brazil. The following combined characters can diagnose the new species from all congeners: head round-shaped; two or three precloacal pores sequentially arranged; 190-199 body annuli; 2-3 lateral annuli; 23-25 caudal annuli; autotomy sites on caudal annuli 7-9; 12-14 dorsal segments on midbody annulus; 14-16 ventral segments on midbody annulus; three supralabials; three infralabials; postmalar row present or absent; dorsum light brown, with cream intersegmental sutures; venter cream. To date, the new species is known only from the Espinhaco Range, highlighting the importance of conservation actions for these mountains. PMID- 26131638 TI - Synopsis of Dorstenia (Moraceae) in Rio Grande do Sul, Southern Brazil. AB - A taxonomic synopsis of Dorstenia (Moraceae) in Rio Grande do Sul (RS), Southern Brazil, is presented. Three species were recorded: D. brasiliensis, D. carautae, a new record for the state of RS, and D. tenuis. All species are described and illustrated through detailed photos of living specimens. A taxonomic key to separate the species, as well as details on distribution, overall phenology, habitat, conservation status and ecology are presented. PMID- 26131639 TI - Glandular trichome density and essential oil composition in leaves and inflorescences of Lippia origanoides Kunth (Verbenaceae) in the Brazilian Cerrado. AB - The essential oils from leaves and inflorescences of Lippia origanoides Kunth present aromatic and medicinal potential and have been used to treat several diseases, including melanoma. In Brazil, L. origanoides is commonly found in campo cerrado and cerrado stricto sensu, physiognomies featured mainly by the differential light conditions to which short and medium-sized plants are subjected. Our aim was to investigate the glandular trichome density and the yield and chemical composition of the essential oils in leaves and inflorescences of L. origanoides from campo cerrado and cerrado stricto sensu. For glandular density analysis, leaves and inflorescences were processed according to conventional techniques for scanning electron microscopy. The essential oils of leaves and inflorescences were obtained by hydrodistillation and identified with gas chromatography. Bracts and sepals showed the highest glandular density, followed by petals and leaves. The glandular density in the abaxial leaf surface was higher in individuals from the campo cerrado. In both populations the essential oil yield was higher in inflorescences than in leaves. The chemical composition of the essential oils varied among individuals from different areas and inside a same population. Our results demonstrated the chemical plasticity of L. origanoides suggesting the importance of monitoring its popular use. PMID- 26131640 TI - Culicoides castelloni sp. nov. from the Brazilian Amazon Region with a revision of the reticulatus species group (Diptera, Ceratopogonidae). AB - A new species of the reticulatus species group, C. castelloni Santarem and Felippe-Bauer, is described and illustrated based on female specimens from the state of Amazonas, Brazil. A systematic key, wing photographs and table with numerical characters of females and a synopsis of 24 species of the Culicoides reticulatus group are presented. This paper presents further new records for seven species of the reticulatus group. PMID- 26131641 TI - Qualitative characteristics of meat from cull cows of different genotypes and age class slaughter under different finishing systems: a meta-analytic approach. AB - The aim of this study was to evaluate, by meta-analysis, the quality of the meat of the cows according to genotype, termination system and age class slaughter. During an online research were identified 15 articles with information related to meat quality of slaughtered cows. The data were grouped according of the genotype of cows being: zebu or continental defined, crossed zebu x british or zebu x continental; according to termination system: feedlot or grassland; according to age of slaughter, where: up to 4 years old (young), 4-8 years old (adult) or more than 8 years old (old). The meat of the continental crossbred cows was softer than the other genotypes, both panel of evaluators and by Shear. The meat of cows finished in feedlot showed higher marbling degree in relation to meat of females finished on grassland. The reduction of the slaughter age of cows improved the meat color. The cow's genotype affects the organoleptic aspects of meat while the finished system and slaughter age affects the sensory aspects of meat. PMID- 26131642 TI - Mathematical and Numerical Modeling of Turbulent Flows. AB - The present work is devoted to the development and implementation of a computational framework to perform numerical simulations of low Mach number turbulent flows over complex geometries. The algorithm under consideration is based on a classical predictor-corrector time integration scheme that employs a projection method for the momentum equations. The domain decomposition strategy is adopted for distributed computing, displaying very satisfactory levels of speed-up and efficiency. The Immersed Boundary Methodology is used to characterize the presence of a complex geometry. Such method demands two separate grids: An Eulerian, where the transport equations are solved with a Finite Volume, second order discretization and a Lagrangian domain, represented by a non structured shell grid representing the immersed geometry. The in-house code developed was fully verified by the Method of Manufactured Solutions, in both Eulerian and Lagrangian domains. The capabilities of the resulting computational framework are illustrated on four distinct cases: a turbulent jet, the Poiseuille flow, as a matter of validation of the implemented Immersed Boundary methodology, the flow over a sphere covering a wide range of Reynolds numbers, and finally, with the intention of demonstrating the applicability of Large Eddy Simulations - LES - in an industrial problem, the turbulent flow inside an industrial fan. PMID- 26131643 TI - Brazilian Science and Research Integrity: Where are We? What Next? AB - Building a world-class scientific community requires first-class ingredients at many different levels: funding, training, management, international collaborations, creativity, ethics, and an understanding of research integrity practices. All over the world, addressing these practices has been high on the science policy agenda of major research systems. Universities have a central role in fostering a culture of research integrity, which has posed additional challenges for faculty, students and administrators - but also opportunities. In Brazil, the leading universities and governmental funding agencies are collaborating on this project, but much remains to be done. PMID- 26131644 TI - Denver Papillae Protocol for Objective Analysis of Fungiform Papillae. AB - The goal of the Denver Papillae Protocol is to use a dichotomous key to define and prioritize the characteristics of fungiform papillae (FP) to ensure consistent scoring between scorers. This protocol builds off of a need that has arisen from the last two decades of taste research using FP as a proxy for taste pore density. FP density has historically been analyzed using Miller & Reedy's 1990 characterizations of their morphology: round, stained lighter, large, and elevated. In this work, the authors forewarned that stricter definitions of FP morphology needed to be outlined. Despite this call to action, follow up literature has been scarce, with most studies continuing to cite Miller & Reedy's original work. Consequently, FP density reports have been highly variable and, combined with small sample sizes, may contribute to the discrepant conclusions on the role of FP in taste sensitivity. The Genetics of Taste Lab explored this apparent inconsistency in counting and found that scorers were individually prioritizing the importance of these characteristics differently and had no guidance for when a papilla had some, but not all, of the reported qualities of FP. The result of this subjectivity is highly variable FP counts of the same tongue image. The Denver Papillae Protocol has been developed to remedy this consequence through use of a dichotomous key that further defines and prioritizes the importance of the characteristics put forth by Miller & Reedy. The proposed method could help create a standard way to quantify FP for researchers in the field of taste and nutritional studies. PMID- 26131645 TI - Planar Gradient Diffusion System to Investigate Chemotaxis in a 3D Collagen Matrix. AB - The importance of cell migration can be seen through the development of human life. When cells migrate, they generate forces and transfer these forces to their surrounding area, leading to cell movement and migration. In order to understand the mechanisms that can alter and/or affect cell migration, one can study these forces. In theory, understanding the fundamental mechanisms and forces underlying cell migration holds the promise of effective approaches for treating diseases and promoting cellular transplantation. Unfortunately, modern chemotaxis chambers that have been developed are usually restricted to two dimensions (2D) and have complex diffusion gradients that make the experiment difficult to interpret. To this end, we have developed, and describe in this paper, a direct-viewing chamber for chemotaxis studies, which allows one to overcome modern chemotaxis chamber obstacles able to measure cell forces and specific concentration within the chamber in a 3D environment to study cell 3D migration. More compelling, this approach allows one to successfully model diffusion through 3D collagen matrices and calculate the coefficient of diffusion of a chemoattractant through multiple different concentrations of collagen, while keeping the system simple and user friendly for traction force microscopy (TFM) and digital volume correlation (DVC) analysis. PMID- 26131646 TI - Perceptions and practices of self-medication in healthcare and nonhealthcare university students in South India. AB - BACKGROUND: The aim was to study and compare knowledge, attitude and practices regarding self-medication in healthcare and nonhealthcare university students. METHODS: Suitably constructed, structured and pretested questionnaires were distributed to 350 students in each group; data were documented in SPSS software version 20.0 and analyzed using chi2-test and multivariate logistic regression analysis. RESULTS: Completed questionnaires only were analyzed, which were 314 and 310 in healthcare and nonhealthcare groups, respectively. The majority of students practiced self-medication (84.4% vs. 68.1%; p<0.001) with the most common indications being fever (46.4% vs. 37.9%; p<0.001) and cough and common cold (30.9% vs. 37%; p=0.004). Most commonly self-medicated drugs were antipyretics (67.9% vs. 52.6%; p=0.03) and multivitamins (28.7% vs. 16.8%; p<0.001). A few of them experienced adverse drug reactions due to self-medication (6.8% vs. 1.9%; p<0.001). Independent risk factors for self-medication were younger age group (OR=2.93, CI 95% 1.09-7.85), storage of medicines at home (OR=2.49, CI 95% 1.21-5.12), healthcare students (OR=2.54, CI 95% 1.72-3.74), higher knowledge scores (OR=1.65, CI 95% 1.08-2.52), those consuming homeopathic preparations (OR=9.19, CI 95% 1.24-68.11), multivitamins (OR=6.7, CI 95% 2.88 15.6) or health supplements (OR=6, CI 95% 2.15-16.74), participants who strongly agreed that self-medication is a part of self-care (OR=3.97, CI 95% 1.56-10.09), and those self-medicating with an old prescription for same illness (OR=0.04, CI 95% 0.01-0.15) or over advice from home (OR=0.11, CI 95% 0.04-0.3). CONCLUSIONS: Though self-medication is common in university students, there is a dearth in their knowledge regarding the same. This highlights the need for increasing awareness among students regarding hazards of self-medication. PMID- 26131647 TI - Transdermal Delivery of Drugs with Microneedles-Potential and Challenges. AB - Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use. PMID- 26131648 TI - Chick Heart Invasion Assay for Testing the Invasiveness of Cancer Cells and the Activity of Potentially Anti-invasive Compounds. AB - The goal of the chick heart assay is to offer a relevant organ culture method to study tumor invasion in three dimensions. The assay can distinguish between invasive and non-invasive cells, and enables study of the effects of test compounds on tumor invasion. Cancer cells - either as aggregates or single cells are confronted with fragments of embryonic chick heart. After organ culture in suspension for a few days or weeks the confronting cultures are fixed and embedded in paraffin for histological analysis. The three-dimensional interaction between the cancer cells and the normal tissue is then reconstructed from serial sections stained with hematoxylin-eosin or after immunohistochemical staining for epitopes in the heart tissue or the confronting cancer cells. The assay is consistent with the recent concept that cancer invasion is the result of molecular interactions between the cancer cells and their neighbouring stromal host elements (myofibroblasts, endothelial cells, extracellular matrix components, etc.). Here, this stromal environment is offered to the cancer cells as a living tissue fragment. Supporting aspects to the relevance of the assay are multiple. Invasion in the assay is in accordance with the criteria of cancer invasion: progressive occupation and replacement in time and space of the host tissue, and invasiveness and non-invasiveness in vivo of the confronting cells generally correlates with the outcome of the assay. Furthermore, the invasion pattern of cells in vivo, as defined by pathologists, is reflected in the histological images in the assay. Quantitative structure-activity relation (QSAR) analysis of the results obtained with numerous potentially anti-invasive organic congener compounds allowed the study of structure-activity relations for flavonoids and chalcones, and known anti-metastatic drugs used in the clinic (e.g., microtubule inhibitors) inhibit invasion in the assay as well. However, the assay does not take into account immunological contributions to cancer invasion. PMID- 26131649 TI - Using the Electroretinogram to Assess Function in the Rodent Retina and the Protective Effects of Remote Limb Ischemic Preconditioning. AB - The ERG is the sum of all retinal activity. The ERG is usually recorded from the cornea, which acts as an antenna that collects and sums signals from the retina. The ERG is a sensitive measure of changes in retinal function that are pan retinal, but is less effective for detecting damage confined to a small area of retina. In the present work we describe how to record the 'flash' ERG, which is the potential generated when the retina is exposed to a brief light flash. We describe methods of anaesthesia, mydriasis and corneal management during recording; how to keep the retina dark adapted; electrode materials and placement; the range and calibration of stimulus energy; recording parameters and the extraction of data. We also describe a method of inducing ischemia in one limb, and how to use the ERG to assess the effects of this remote-from-the-retina ischemia on retinal function after light damage. A two-flash protocol is described which allows isolation of the cone-driven component of the dark-adapted ERG, and thereby the separation of the rod and cone components. Because it can be recorded with techniques that are minimally invasive, the ERG has been widely used in studies of the physiology, pharmacology and toxicology of the retina. We describe one example of this usefulness, in which the ERG is used to assess the function of the light-damaged retina, with and without a neuroprotective intervention; preconditioning by remote ischemia. PMID- 26131650 TI - New Risk Factor for SIDS? Peaks in Cot Deaths Associated with Heat Waves. PMID- 26131651 TI - In Vitro and In Vivo Model to Study Bacterial Adhesion to the Vessel Wall Under Flow Conditions. AB - In order to cause endovascular infections and infective endocarditis, bacteria need to be able to adhere to the vessel wall while being exposed to the shear stress of flowing blood. To identify the bacterial and host factors that contribute to vascular adhesion of microorganisms, appropriate models that study these interactions under physiological shear conditions are needed. Here, we describe an in vitro flow chamber model that allows to investigate bacterial adhesion to different components of the extracellular matrix or to endothelial cells, and an intravital microscopy model that was developed to directly visualize the initial adhesion of bacteria to the splanchnic circulation in vivo. These methods can be used to identify the bacterial and host factors required for the adhesion of bacteria under flow. We illustrate the relevance of shear stress and the role of von Willebrand factor for the adhesion of Staphylococcus aureus using both the in vitro and in vivo model. PMID- 26131652 TI - The representativeness of the Arquivos Brasileiros de Cardiologia for Brazilian Cardiology Science. PMID- 26131653 TI - Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats. AB - Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor learning and execution is of critical importance in order to understand the principles and processes that underlie motor function. Here we present a paradigm to study movement acquisition within a daily session of training (within-session) representing the fast learning component and primary acquisition as well as skilled motor learning over several training sessions (between-session) representing the slow learning component and consolidation of the learned task. This behavioral paradigm increases the degree of difficulty and complexity of the motor skill task due to two features: First, the animal realigns its body prior to each pellet retrieval forcing renewed orientation and preventing movement execution from the same angle. Second, pellets are grasped from a vertical post that matches the diameter of the pellet and is placed in front of the cage. This requires a precise grasp for successful pellet retrieval and thus prevents simple pulling of the pellet towards the animal. In combination with novel genetics, imaging and electrophysiological technologies, this behavioral method will aid to understand the morphological, anatomical and molecular underpinnings of motor learning and memory. PMID- 26131658 TI - Impact of Increasing Coverage for Select Smoking Cessation Therapies With no Out of-Pocket Cost Among the Medicaid Population in Alabama, Georgia, and Maine. AB - Prevalence of smoking is particularly high among individuals with low socioeconomic status and who may be receiving Medicaid benefits. This study evaluates the public health and economic impact of providing coverage for nicotine replacement therapy with no out-of-pocket cost to the adult Medicaid population in Alabama, Georgia, and Maine, in 2012. We estimated the increase in the number of quitters and the savings in Medicaid medical expenditures associated with expanding Medicaid coverage of nicotine replacement therapy to the entire adult Medicaid population in the 3 states. With an expansion of Medicaid coverage of nicotine replacement therapy from only pregnant women to all adult Medicaid enrollees, the state of Alabama might expect 1873 to 2810 additional quitters ($526,203 and $789,305 in savings of annual Medicaid expenditures from both federal and state funds), Georgia 2911 to 4367 additional quits ($1,455,606 and $2,183,409 savings), and Maine 1511 to 2267 additional quits in ($431,709 and $647,564 savings). The expansion of coverage for smoking cessation therapy with no out-of-pocket cost could reduce Medicaid expenditures in all 3 states. PMID- 26131659 TI - Linking structural features of protein complexes and biological function. AB - Protein-protein interaction (PPI) establishes the central basis for complex cellular networks in a biological cell. Association of proteins with other proteins occurs at varying affinities, yet with a high degree of specificity. PPIs lead to diverse functionality such as catalysis, regulation, signaling, immunity, and inhibition, playing a crucial role in functional genomics. The molecular principle of such interactions is often elusive in nature. Therefore, a comprehensive analysis of known protein complexes from the Protein Data Bank (PDB) is essential for the characterization of structural interface features to determine structure-function relationship. Thus, we analyzed a nonredundant dataset of 278 heterodimer protein complexes, categorized into major functional classes, for distinguishing features. Interestingly, our analysis has identified five key features (interface area, interface polar residue abundance, hydrogen bonds, solvation free energy gain from interface formation, and binding energy) that are discriminatory among the functional classes using Kruskal-Wallis rank sum test. Significant correlations between these PPI interface features amongst functional categories are also documented. Salt bridges correlate with interface area in regulator-inhibitors (r = 0.75). These representative features have implications for the prediction of potential function of novel protein complexes. The results provide molecular insights for better understanding of PPIs and their relation to biological functions. PMID- 26131660 TI - Cre Activated and Inactivated Recombinant Adeno-Associated Viral Vectors for Neuronal Anatomical Tracing or Activity Manipulation. AB - Recombinant adeno-associated viruses (rAAVs) transcriptionally activated by Cre recombinase (Cre-On) are powerful tools for determining the anatomy and function of genetically defined neuronal types in transgenic Cre driver mice. Here we describe how rAAVs transcriptionally inactivated by Cre (Cre-Off) can be used in conjunction with Cre-On rAAVs or genomic Cre-reporter alleles to study brain circuits. Intracranial injection of Cre-On/Cre-Off rAAVs into spatially intermingled Cre(+) and Cre(-) neurons allows these populations to be differentially labeled or manipulated within individual animals. This comparison helps define the unique properties of Cre(+) neurons, highlighting the specialized role they play in their constituent brain circuits. This protocol touches on the conceptual and experimental background of Cre-Off rAAV systems, including caveats and methods of validation. PMID- 26131661 TI - Time-Lapse Imaging of Glial-Axonal Interactions. AB - In the central nervous system (CNS), myelin is formed by oligodendrocytes that are derived from precursor cells, known as oligodendrocyte precursor cells (OPCs). Successive stages of OPC interactions with the axons can be visualized in vitro and ex vivo using mixed neural cell cultures and pieces of intact spinal cord, respectively. OPCs and their differentiation can be imaged using cell-type specific markers or green fluorescent protein (GFP) tags. This protocol describes methodology for generating these two systems for time-lapse imaging of dynamic cell interactions using fluorescent and 2-photon microscopy. PMID- 26131662 TI - The Use of Herpes Simplex Virus in Ex Vivo Slice Culture. AB - Herpes simplex virus (HSV) can be used for a wide range of genetic manipulations in ex vivo slices of central nervous system tissue from both young and adult rodents. The fast expression of the HSV viral-mediated gene transfer, which can be engineered to produce cell-type specificity, can be utilized in slice cultures for a variety of purposes over a 1- to 4-day period with spatial and temporal specificity. This protocol exploits the rapid expression of HSV viral vectors by utilizing slice culture for electrophysiological recordings, avoiding the need to do intracranial viral injections. Brain slice cultures maintain many aspects of in vivo biology, including functional local synaptic circuitry with preserved brain architecture, while allowing good experimental access and precise control of the extracellular environment, making them ideal platforms for quick access to evaluate expression effects of HSV viral-mediated gene transfer on the molecular and cellular properties of specific neurons. This protocol provides an easy way to study neuronal function following viral expression of a gene of interest. PMID- 26131663 TI - Attentional Set-Shifting Paradigm in the Rat. AB - The attentional set-shifting task (ASST) is the rat version of the intra dimensional/extra-dimensional (ID/ED) test and was developed fifteen years ago. Damage to the medial frontal cortex results in a failure to "unlearn" old contingencies, i.e., impairs ED set shifting. As such, the task measures cognitive flexibility that can be compromised both in schizophrenia and depression as well as in animal models of these diseases. PMID- 26131664 TI - Rose Bengal Photothrombosis by Confocal Optical Imaging In Vivo: A Model of Single Vessel Stroke. AB - In vivo imaging techniques have increased in utilization due to recent advances in imaging dyes and optical technologies, allowing for the ability to image cellular events in an intact animal. Additionally, the ability to induce physiological disease states such as stroke in vivo increases its utility. The technique described herein allows for physiological assessment of cellular responses within the CNS following a stroke and can be adapted for other pathological conditions being studied. The technique presented uses laser excitation of the photosensitive dye Rose Bengal in vivo to induce a focal ischemic event in a single blood vessel. The video protocol demonstrates the preparation of a thin-skulled cranial window over the somatosensory cortex in a mouse for the induction of a Rose Bengal photothrombotic event keeping injury to the underlying dura matter and brain at a minimum. Surgical preparation is initially performed under a dissecting microscope with a custom-made surgical/imaging platform, which is then transferred to a confocal microscope equipped with an inverted objective adaptor. Representative images acquired utilizing this protocol are presented as well as time-lapse sequences of stroke induction. This technique is powerful in that the same area can be imaged repeatedly on subsequent days facilitating longitudinal in vivo studies of pathological processes following stroke. PMID- 26131665 TI - A Novel Two-Tier Cooperative Caching Mechanism for the Optimization of Multi Attribute Periodic Queries in Wireless Sensor Networks. AB - Wireless sensor networks, serving as an important interface between physical environments and computational systems, have been used extensively for supporting domain applications, where multiple-attribute sensory data are queried from the network continuously and periodically. Usually, certain sensory data may not vary significantly within a certain time duration for certain applications. In this setting, sensory data gathered at a certain time slot can be used for answering concurrent queries and may be reused for answering the forthcoming queries when the variation of these data is within a certain threshold. To address this challenge, a popularity-based cooperative caching mechanism is proposed in this article, where the popularity of sensory data is calculated according to the queries issued in recent time slots. This popularity reflects the possibility that sensory data are interested in the forthcoming queries. Generally, sensory data with the highest popularity are cached at the sink node, while sensory data that may not be interested in the forthcoming queries are cached in the head nodes of divided grid cells. Leveraging these cooperatively cached sensory data, queries are answered through composing these two-tier cached data. Experimental evaluation shows that this approach can reduce the network communication cost significantly and increase the network capability. PMID- 26131666 TI - An Efficient Biometric-Based Algorithm Using Heart Rate Variability for Securing Body Sensor Networks. AB - Body Sensor Network (BSN) is a network of several associated sensor nodes on, inside or around the human body to monitor vital signals, such as, Electroencephalogram (EEG), Photoplethysmography (PPG), Electrocardiogram (ECG), etc. Each sensor node in BSN delivers major information; therefore, it is very significant to provide data confidentiality and security. All existing approaches to secure BSN are based on complex cryptographic key generation procedures, which not only demands high resource utilization and computation time, but also consumes large amount of energy, power and memory during data transmission. However, it is indispensable to put forward energy efficient and computationally less complex authentication technique for BSN. In this paper, a novel biometric based algorithm is proposed, which utilizes Heart Rate Variability (HRV) for simple key generation process to secure BSN. Our proposed algorithm is compared with three data authentication techniques, namely Physiological Signal based Key Agreement (PSKA), Data Encryption Standard (DES) and Rivest Shamir Adleman (RSA). Simulation is performed in Matlab and results suggest that proposed algorithm is quite efficient in terms of transmission time utilization, average remaining energy and total power consumption. PMID- 26131667 TI - A Double Transducer for High Precision Ultrasonic Time-Domain Reflectometry Measurements. AB - Membrane fouling, where unwanted particles accumulate on the membrane surface and reduce its permeability, causes problems in membrane filtration processes. With ultrasonic time-domain reflectometry (UTDR) it is possible to measure the extent of membrane fouling and hence take actions to minimize it. However, the usability of UTDR is very limited to constant filtration conditions if the sonic velocity, which has a great impact on UTDR measurement accuracy, is unknown. With a reference transducer the actual sonic velocity can be measured. This requires another transducer to be installed in the module, where there may be only limited space or the module dimensions may not be suitable for the reference transducer. A double transducer described in this study eliminates the need for a separate reference transducer because in the double transducer the reference measurement is included in the design of the transducer holder. Two sensors in the same holder require less space. Other advantage is that the double transducer can be placed near the measurement target and hence the local sonic velocity can be determined. PMID- 26131668 TI - Using Wireless Sensor Networks and Trains as Data Mules to Monitor Slab Track Infrastructures. AB - Recently, slab track systems have arisen as a safer and more sustainable option for high speed railway infrastructures, compared to traditional ballasted tracks. Integrating Wireless Sensor Networks within these infrastructures can provide structural health related data that can be used to evaluate their degradation and to not only detect failures but also to predict them. The design of such systems has to deal with a scenario of large areas with inaccessible zones, where neither Internet coverage nor electricity supply is guaranteed. In this paper we propose a monitoring system for slab track systems that measures vibrations and displacements in the track. Collected data is transmitted to passing trains, which are used as data mules to upload the information to a remote control center. On arrival at the station, the data is stored in a database, which is queried by an application in order to detect and predict failures. In this paper, different communication architectures are designed and tested to select the most suitable system meeting such requirements as efficiency, low cost and data accuracy. In addition, to ensure communication between the sensing devices and the train, the communication system must take into account parameters such as train speed, antenna coverage, band and frequency. PMID- 26131669 TI - A Secure Routing Protocol for Wireless Sensor Networks Considering Secure Data Aggregation. AB - The commonly unattended and hostile deployments of WSNs and their resource constrained sensor devices have led to an increasing demand for secure energy efficient protocols. Routing and data aggregation receive the most attention since they are among the daily network routines. With the awareness of such demand, we found that so far there has been no work that lays out a secure routing protocol as the foundation for a secure data aggregation protocol. We argue that the secure routing role would be rendered useless if the data aggregation scheme built on it is not secure. Conversely, the secure data aggregation protocol needs a secure underlying routing protocol as its foundation in order to be effectively optimal. As an attempt for the solution, we devise an energy-aware protocol based on LEACH and ESPDA that combines secure routing protocol and secure data aggregation protocol. We then evaluate its security effectiveness and its energy-efficiency aspects, knowing that there are always trade-off between both. PMID- 26131670 TI - Tool for Semiautomatic Labeling of Moving Objects in Video Sequences: TSLAB. AB - An advanced and user-friendly tool for fast labeling of moving objects captured with surveillance sensors is proposed, which is available to the public. This tool allows the creation of three kinds of labels: moving objects, shadows and occlusions. These labels are created at both the pixel level and object level, which makes them suitable to assess the quality of both moving object detection strategies and tracking algorithms. The labeling can be performed easily and quickly thanks to a very friendly graphical user interface that allows one to automatize many common operations. This interface also includes some semiautomatic advanced tools that simplify the labeling tasks and drastically reduce the time required to obtain high-quality results. PMID- 26131671 TI - Recognition of a Phase-Sensitivity OTDR Sensing System Based on Morphologic Feature Extraction. AB - This paper proposes a novel feature extraction method for intrusion event recognition within a phase-sensitive optical time-domain reflectometer (Phi-OTDR) sensing system. Feature extraction of time domain signals in these systems is time-consuming and may lead to inaccuracies due to noise disturbances. The recognition accuracy and speed of current systems cannot meet the requirements of Phi-OTDR online vibration monitoring systems. In the method proposed in this paper, the time-space domain signal is used for feature extraction instead of the time domain signal. Feature vectors are obtained from morphologic features of time-space domain signals. A scatter matrix is calculated for the feature selection. Experiments show that the feature extraction method proposed in this paper can greatly improve recognition accuracies, with a lower computation time than traditional methods, i.e., a recognition accuracy of 97.8% can be achieved with a recognition time of below 1 s, making it is very suitable for Phi-OTDR system online vibration monitoring. PMID- 26131672 TI - A Novel Feature Extraction Approach Using Window Function Capturing and QPSO-SVM for Enhancing Electronic Nose Performance. AB - In this paper, a novel feature extraction approach which can be referred to as moving window function capturing (MWFC) has been proposed to analyze signals of an electronic nose (E-nose) used for detecting types of infectious pathogens in rat wounds. Meanwhile, a quantum-behaved particle swarm optimization (QPSO) algorithm is implemented in conjunction with support vector machine (SVM) for realizing a synchronization optimization of the sensor array and SVM model parameters. The results prove the efficacy of the proposed method for E-nose feature extraction, which can lead to a higher classification accuracy rate compared to other established techniques. Meanwhile it is interesting to note that different classification results can be obtained by changing the types, widths or positions of windows. By selecting the optimum window function for the sensor response, the performance of an E-nose can be enhanced. PMID- 26131673 TI - Articulated Non-Rigid Point Set Registration for Human Pose Estimation from 3D Sensors. AB - We propose a generative framework for 3D human pose estimation that is able to operate on both individual point sets and sequential depth data. We formulate human pose estimation as a point set registration problem, where we propose three new approaches to address several major technical challenges in this research. First, we integrate two registration techniques that have a complementary nature to cope with non-rigid and articulated deformations of the human body under a variety of poses. This unique combination allows us to handle point sets of complex body motion and large pose variation without any initial conditions, as required by most existing approaches. Second, we introduce an efficient pose tracking strategy to deal with sequential depth data, where the major challenge is the incomplete data due to self-occlusions and view changes. We introduce a visible point extraction method to initialize a new template for the current frame from the previous frame, which effectively reduces the ambiguity and uncertainty during registration. Third, to support robust and stable pose tracking, we develop a segment volume validation technique to detect tracking failures and to re-initialize pose registration if needed. The experimental results on both benchmark 3D laser scan and depth datasets demonstrate the effectiveness of the proposed framework when compared with state-of-the-art algorithms. PMID- 26131674 TI - A Novel 2D-to-3D Video Conversion Method Using Time-Coherent Depth Maps. AB - In this paper, we propose a novel 2D-to-3D video conversion method for 3D entertainment applications. 3D entertainment is getting more and more popular and can be found in many contexts, such as TV and home gaming equipment. 3D image sensors are a new method to produce stereoscopic video content conveniently and at a low cost, and can thus meet the urgent demand for 3D videos in the 3D entertaiment market. Generally, 2D image sensor and 2D-to-3D conversion chip can compose a 3D image sensor. Our study presents a novel 2D-to-3D video conversion algorithm which can be adopted in a 3D image sensor. In our algorithm, a depth map is generated by combining global depth gradient and local depth refinement for each frame of 2D video input. Global depth gradient is computed according to image type while local depth refinement is related to color information. As input 2D video content consists of a number of video shots, the proposed algorithm reuses the global depth gradient of frames within the same video shot to generate time-coherent depth maps. The experimental results prove that this novel method can adapt to different image types, reduce computational complexity and improve the temporal smoothness of generated 3D video. PMID- 26131675 TI - Coded Cooperation for Multiway Relaying in Wireless Sensor Networks. AB - Wireless sensor networks have been considered as an enabling technology for constructing smart cities. One important feature of wireless sensor networks is that the sensor nodes collaborate in some manner for communications. In this manuscript, we focus on the model of multiway relaying with full data exchange where each user wants to transmit and receive data to and from all other users in the network. We derive the capacity region for this specific model and propose a coding strategy through coset encoding. To obtain good performance with practical codes, we choose spatially-coupled LDPC (SC-LDPC) codes for the coded cooperation. In particular, for the message broadcasting from the relay, we construct multi-edge-type (MET) SC-LDPC codes by repeatedly applying coset encoding. Due to the capacity-achieving property of the SC-LDPC codes, we prove that the capacity region can theoretically be achieved by the proposed MET SC LDPC codes. Numerical results with finite node degrees are provided, which show that the achievable rates approach the boundary of the capacity region in both binary erasure channels and additive white Gaussian channels. PMID- 26131676 TI - Location Privacy for Mobile Crowd Sensing through Population Mapping. AB - Opportunistic sensing allows applications to "task" mobile devices to measure context in a target region. For example, one could leverage sensor-equipped vehicles to measure traffic or pollution levels on a particular street or users' mobile phones to locate (Bluetooth-enabled) objects in their vicinity. In most proposed applications, context reports include the time and location of the event, putting the privacy of users at increased risk: even if identifying information has been removed from a report, the accompanying time and location can reveal sufficient information to de-anonymize the user whose device sent the report. We propose and evaluate a novel spatiotemporal blurring mechanism based on tessellation and clustering to protect users' privacy against the system while reporting context. Our technique employs a notion of probabilistic k-anonymity; it allows users to perform local blurring of reports efficiently without an online anonymization server before the data are sent to the system. The proposed scheme can control the degree of certainty in location privacy and the quality of reports through a system parameter. We outline the architecture and security properties of our approach and evaluate our tessellation and clustering algorithm against real mobility traces. PMID- 26131677 TI - Sensorless FOC Performance Improved with On-Line Speed and Rotor Resistance Estimator Based on an Artificial Neural Network for an Induction Motor Drive. AB - Three-phase induction motor drive requires high accuracy in high performance processes in industrial applications. Field oriented control, which is one of the most employed control schemes for induction motors, bases its function on the electrical parameter estimation coming from the motor. These parameters make an electrical machine driver work improperly, since these electrical parameter values change at low speeds, temperature changes, and especially with load and duty changes. The focus of this paper is the real-time and on-line electrical parameters with a CMAC-ADALINE block added in the standard FOC scheme to improve the IM driver performance and endure the driver and the induction motor lifetime. Two kinds of neural network structures are used; one to estimate rotor speed and the other one to estimate rotor resistance of an induction motor. PMID- 26131678 TI - A Novel Machine Vision System for the Inspection of Micro-Spray Nozzle. AB - In this study, we present an application of neural network and image processing techniques for detecting the defects of an internal micro-spray nozzle. The defect regions were segmented by Canny edge detection, a randomized algorithm for detecting circles and a circle inspection (CI) algorithm. The gray level co occurrence matrix (GLCM) was further used to evaluate the texture features of the segmented region. These texture features (contrast, entropy, energy), color features (mean and variance of gray level) and geometric features (distance variance, mean diameter and diameter ratio) were used in the classification procedures. A back-propagation neural network classifier was employed to detect the defects of micro-spray nozzles. The methodology presented herein effectively works for detecting micro-spray nozzle defects to an accuracy of 90.71%. PMID- 26131679 TI - A Synthetic Bandwidth Method for High-Resolution SAR Based on PGA in the Range Dimension. AB - The synthetic bandwidth technique is an effective method to achieve ultra-high range resolution in an SAR system. There are mainly two challenges in its implementation. The first one is the estimation and compensation of system errors, such as the timing deviation and the amplitude-phase error. Due to precision limitation of the radar instrument, construction of the sub-band signals becomes much more complicated with these errors. The second challenge lies in the combination method, that is how to fit the sub-band signals together into a much wider bandwidth. In this paper, a novel synthetic bandwidth approach is presented. It considers two main errors of the multi-sub-band SAR system and compensates them by a two-order PGA (phase gradient auto-focus)-based method, named TRPGA. Furthermore, an improved cut-paste method is proposed to combine the signals in the frequency domain. It exploits the redundancy of errors and requires only a limited amount of data in the azimuth direction for error estimation. Moreover, the up-sampling operation can be avoided in the combination process. Imaging results based on both simulated and real data are presented to validate the proposed approach. PMID- 26131680 TI - Fruit and Vegetable Quality Assessment via Dielectric Sensing. AB - The demand for improved food quality has been accompanied by a technological boost. This fact enhances the possibility of improving the quality of horticultural products, leading towards healthier consumption of fruits and vegetables. A better electrical characterization of the dielectric properties of fruits and vegetables is required for this purpose. Moreover, a focused study of dielectric spectroscopy and advanced dielectric sensing is a highly interesting topic. This review explains the dielectric property basics and classifies the dielectric spectroscopy measurement techniques. It comprehensively and chronologically covers the dielectric experiments explored for fruits and vegetables, along with their appropriate sensing instrumentation, analytical modelling methods and conclusions. An in-depth definition of dielectric spectroscopy and its usefulness in the electric characterization of food materials is presented, along with the various sensor techniques used for dielectric measurements. The collective data are tabulated in a summary of the dielectric findings in horticultural field investigations, which will facilitate more advanced and focused explorations in the future. PMID- 26131684 TI - Cavity-Coupled Plasmonic Device with Enhanced Sensitivity and Figure-of-Merit. AB - Using full-wafer processing, we demonstrate a sophisticated nanotechnology for the realization of an ultrahigh sensitive cavity-coupled plasmonic device that combines the advantages of Fabry-Perot microcavities with those of metallic nanostructures. Coupling the plasmonic nanostructures to a Fabry-Perot microcavity creates compound modes, which have the characteristics of both Fabry Perot and localized surface plasmon resonance (LSPR) modes, boosting the sensitivity and figure-of-merit of the structure. The significant trait of the proposed device is that the sample to be measured is located in the substrate region and is probed by the compound modes. It is demonstrated that the sensitivity of the compound modes is much higher than that of LSPR of plasmonic nanostructures or the pure Fabry-Perot modes of the optical microcavity. The response of the device is also investigated numerically and the agreement between measurements and calculations is excellent. The key features of the device introduced in this work are applicable for the realization of ultrahigh sensitive plasmonic devices for biosensing, optoelectronics, and related technologies. PMID- 26131685 TI - What's NORMal for Fracking? Estimating Total Radioactivity of Produced Fluids. PMID- 26131686 TI - Somatostatin in the rat rostral ventrolateral medulla: Origins and mechanism of action. AB - Somatostatin (SST) or agonists of the SST-2 receptor (sst2 ) in the rostral ventrolateral medulla (RVLM) lower sympathetic nerve activity, arterial pressure, and heart rate, or when administered within the Botzinger region, evoke apneusis. Our aims were to describe the mechanisms responsible for the sympathoinhibitory effects of SST on bulbospinal neurons and to identify likely sources of RVLM SST release. Patch clamp recordings were made from bulbospinal RVLM neurons (n = 31) in brainstem slices prepared from juvenile rat pups. Overall, 58% of neurons responded to SST, displaying an increase in conductance that reversed at -93 mV, indicative of an inwardly rectifying potassium channel (GIRK) mechanism. Blockade of sst2 abolished this effect, but application of tetrodotoxin did not, indicating that the SST effect is independent of presynaptic activity. Fourteen bulbospinal RVLM neurons were recovered for immunohistochemistry; nine were SST insensitive and did not express sst2a . Three out of five responsive neurons were sst2a -immunoreactive. Neurons that contained preprosomatostatin mRNA and cholera toxin-B retrogradely transported from the RVLM were detected in: paratrigeminal nucleus, lateral parabrachial nucleus, Kolliker-Fuse nucleus, ventrolateral periaqueductal gray area, central nucleus of the amygdala, sublenticular extended amygdala, interstitial nucleus of the posterior limb of the anterior commissure nucleus, and bed nucleus of the stria terminalis. Thus, those brain regions are putative sources of endogenous SST release that, when activated, may evoke sympathoinhibitory effects via interactions with subsets of sympathetic premotor neurons that express sst2 . PMID- 26131688 TI - Selective Hydrogenation of Nitriles to Primary Amines Catalyzed by a Cobalt Pincer Complex. AB - The catalytic hydrogenation of nitriles to primary amines represents an atom efficient and environmentally benign reduction methodology in organic chemistry. This has been accomplished in recent years mainly with precious-metal-based catalysts, with a single exception. Here we report the first homogeneous Co catalyzed hydrogenation of nitriles to primary amines. Several (hetero)aromatic, benzylic, and aliphatic nitriles undergo hydrogenation to the corresponding primary amines in good to excellent yields under the reaction conditions. PMID- 26131687 TI - Measurement of Maximum Isometric Force Generated by Permeabilized Skeletal Muscle Fibers. AB - Analysis of the contractile properties of chemically skinned, or permeabilized, skeletal muscle fibers offers a powerful means by which to assess muscle function at the level of the single muscle cell. Single muscle fiber studies are useful in both basic science and clinical studies. For basic studies, single muscle fiber contractility measurements allow investigation of fundamental mechanisms of force production, and analysis of muscle function in the context of genetic manipulations. Clinically, single muscle fiber studies provide useful insight into the impact of injury and disease on muscle function, and may be used to guide the understanding of muscular pathologies. In this video article we outline the steps required to prepare and isolate an individual skeletal muscle fiber segment, attach it to force-measuring apparatus, activate it to produce maximum isometric force, and estimate its cross-sectional area for the purpose of normalizing the force produced. PMID- 26131689 TI - Alkali Metal Suboxometalates-Structural Chemistry between Salts and Metals. AB - The crystal structures of the new cesium-poor alkali metal suboxometalates Cs10MO5 (M = Al, Ga, Fe) show both metallic and ionic bonding following the formal description (Cs(+))10(MO4(5-))(O(2-)).3e(-). Comparable to the cesium-rich suboxometalates Cs9MO4 (M = Al, Ga, In, Fe, Sc) with ionic subdivision (Cs(+))9(MO4(5-)).4e(-), they contain an oxometalate anion [M(III)O4](5-) embedded in a metallic matrix of cesium atoms. Columnlike building units form with prevalent ionic bonding inside and metallic bonding on the outer surface. In the cesium-rich suboxometalates Cs9MO4, additional cesium atoms with no contact to any anion are inserted between columns of the formal composition [Cs8MO4]. In the cesium-poor suboxometalates Cs10MO5, the same columns are extended by face sharing [Cs6O] units, and no additional cesium atoms are present. The terms "cesium-rich" and "cesium-poor" here refer to the Cs:O ratio. The new suboxometalates Cs10MO5 crystallize in two modifications with new structure types. The orthorhombic modification adopts a structure with four formula units per unit cell in space group Pnnm with a = 11.158(3) A, b = 23.693(15) A, and c = 12.229(3) A for Cs10AlO5. The monoclinic modification crystallizes with eight formula units per unit cell in space group C2/c with a = 21.195(3) A, b = 12.480(1) A, c = 24.120(4) A, and beta = 98.06(1) degrees for Cs10AlO5. Limits to phase formation are given by the restriction that the M atoms must be trivalent and by geometric size restrictions for the insertion of [Cs6O] blocks in Cs10MO5. All of the suboxometalate structures show similar structural details and form mixed crystal series with statistical occupation for the M elements following the patterns Cs9(M(1)xM(2)1-x)O4 and Cs10(M(1)xM(2)1-x)O5. The suboxometalates are a new example of ordered intergrowth of ionic and metallic structure elements, allowing for the combination of properties related to both ionic and metallic materials. PMID- 26131690 TI - Follicular variant papillary thyroid carcinoma in a pediatric population. AB - BACKGROUND: Follicular variant of papillary thyroid carcinoma (FVPTC) has been shown to be an intermediate entity between papillary (PTC) and follicular/Hurtle cell (FTC) thyroid carcinoma in adults. However, the tumor characteristics and prognosis of FVPTCs has not been studied in the pediatric population and is the focus of the current study METHODS: All pediatric patients <= 19 years of age with differentiated thyroid cancer (PTC, FVPTC, or FTC) were identified from the SEER registry from 1988-2009. Patients were divided into groups based on their histology. Adjusted odds ratios (ORs) for demographic, tumor, and treatment characteristics, as well as hazard ratios (HRs) for overall (OS) and disease specific survival (DSS) were calculated for FVPTC. RESULTS: Of 1,956 patients, 445 (22.7%) had FVPTC. Compared to PTCs, FVPTCs were larger (OR: 2.03, CI:1.35 3.06), node negative (OR: 2.26, CI:1.61-3.19), occurred more often in patients < 15 years of age (OR: 1.58, CI:1.10-2.27), and had a partial thyroidectomy (OR: 1.61, CI:1.01-2.57). Conversely, compared to FTC, FVPTCs tumors were smaller (OR: 2.78, CI:1.70-4.53), node positive (OR: 5.26, CI:2.74-10.11), a first cancer (OR: 4.98, CI:2.48-9.99), and more often had a total thyroidectomy (OR: 2.84, CI:1.70 4.76). Only tumor size > 4 cm (HR: 13.92, CI:1.24-156.72) influenced OS for patients with FVPTC. There was no significant difference in OS or DSS between groups. CONCLUSIONS: In pediatric patients <= 19 years of age, FVPTCs have intermediate tumor features compared to PTC and FTC, but a similar OS and DSS. All pediatric patients with thyroid cancer require lifelong surveillance. However, FVPTCs > 4 cm may warrant closer follow-up due to an increased risk of death. PMID- 26131691 TI - Methotrexate Is a JAK/STAT Pathway Inhibitor. AB - BACKGROUND: The JAK/STAT pathway transduces signals from multiple cytokines and controls haematopoiesis, immunity and inflammation. In addition, pathological activation is seen in multiple malignancies including the myeloproliferative neoplasms (MPNs). Given this, drug development efforts have targeted the pathway with JAK inhibitors such as ruxolitinib. Although effective, high costs and side effects have limited its adoption. Thus, a need for effective low cost treatments remains. METHODS & FINDINGS: We used the low-complexity Drosophila melanogaster pathway to screen for small molecules that modulate JAK/STAT signalling. This screen identified methotrexate and the closely related aminopterin as potent suppressors of STAT activation. We show that methotrexate suppresses human JAK/STAT signalling without affecting other phosphorylation-dependent pathways. Furthermore, methotrexate significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F, a mutation associated with most human MPNs. Methotrexate acts independently of dihydrofolate reductase (DHFR) and is comparable to the JAK1/2 inhibitor ruxolitinib. However, cells treated with methotrexate still retain their ability to respond to physiological levels of the ligand erythropoietin. CONCLUSIONS: Aminopterin and methotrexate represent the first chemotherapy agents developed and act as competitive inhibitors of DHFR. Methotrexate is also widely used at low doses to treat inflammatory and immune mediated conditions including rheumatoid arthritis. In this low-dose regime, folate supplements are given to mitigate side effects by bypassing the biochemical requirement for DHFR. Although independent of DHFR, the mechanism-of action underlying the low-dose effects of methotrexate is unknown. Given that multiple pro-inflammatory cytokines signal through the pathway, we suggest that suppression of the JAK/STAT pathway is likely to be the principal anti inflammatory and immunosuppressive mechanism-of-action of low-dose methotrexate. In addition, we suggest that patients with JAK/STAT-associated haematological malignancies may benefit from low-dose methotrexate treatments. While the JAK1/2 inhibitor ruxolitinib is effective, a L43,200 annual cost precludes widespread adoption. With an annual methotrexate cost of around L32, our findings represent an important development with significant future potential. PMID- 26131692 TI - Human Ocular Epithelial Cells Endogenously Expressing SOX2 and OCT4 Yield High Efficiency of Pluripotency Reprogramming. AB - A variety of pluripotency reprogramming frequencies from different somatic cells has been observed, indicating cell origin is a critical contributor for efficiency of pluripotency reprogramming. Identifying the cell sources for efficient induced pluripotent stem cells (iPSCs) generation, and defining its advantages or disadvantages on reprogramming, is therefore important. Human ocular tissue-derived conjunctival epithelial cells (OECs) exhibited endogenous expression of reprogramming factors OCT4A (the specific OCT 4 isoform on pluripotency reprogramming) and SOX2. We therefore determined whether OECs could be used for high efficiency of iPSCs generation. We compared the endogenous expression levels of four pluripotency factors and the pluripotency reprograming efficiency of human OECs with that of ocular stromal cells (OSCs). Real-time PCR, microarray analysis, Western blotting and immunostaining assays were employed to compare OECiPSCs with OSCiPSCs on molecular bases of reprogramming efficiency and preferred lineage-differentiation potential. Using the traditional KMOS (KLF4, C MYC, OCT4 and SOX2) reprogramming protocol, we confirmed that OECs, endogenously expressing reprogramming factors OCT4A and SOX2, yield very high efficiency of iPSCs generation (~1.5%). Furthermore, higher efficiency of retinal pigmented epithelial differentiation (RPE cells) was observed in OECiPSCs compared to OSCiPSCs or skin fibroblast iMR90iPSCs. The findings in this study suggest that conjunctival-derived epithelial (OECs) cells can be easier converted to iPSCs than conjunctival-derived stromal cells (OSCs). This cell type may also have advantages in retinal pigmented epithelial differentiation. PMID- 26131693 TI - Unveiling Inherent Degeneracies in Determining Population-Weighted Ensembles of Interdomain Orientational Distributions Using NMR Residual Dipolar Couplings: Application to RNA Helix Junction Helix Motifs. AB - A growing number of studies employ time-averaged experimental data to determine dynamic ensembles of biomolecules. While it is well-known that different ensembles can satisfy experimental data to within error, the extent and nature of these degeneracies, and their impact on the accuracy of the ensemble determination remains poorly understood. Here, we use simulations and a recently introduced metric for assessing ensemble similarity to explore degeneracies in determining ensembles using NMR residual dipolar couplings (RDCs) with specific application to A-form helices in RNA. Various target ensembles were constructed representing different domain-domain orientational distributions that are confined to a topologically restricted (<10%) conformational space. Five independent sets of ensemble averaged RDCs were then computed for each target ensemble and a "sample and select" scheme used to identify degenerate ensembles that satisfy RDCs to within experimental uncertainty. We find that ensembles with different ensemble sizes and that can differ significantly from the target ensemble (by as much as ?Omega ~ 0.4 where ?Omega varies between 0 and 1 for maximum and minimum ensemble similarity, respectively) can satisfy the ensemble averaged RDCs. These deviations increase with the number of unique conformers and breadth of the target distribution, and result in significant uncertainty in determining conformational entropy (as large as 5 kcal/mol at T = 298 K). Nevertheless, the RDC-degenerate ensembles are biased toward populated regions of the target ensemble, and capture other essential features of the distribution, including the shape. Our results identify ensemble size as a major source of uncertainty in determining ensembles and suggest that NMR interactions such as RDCs and spin relaxation, on their own, do not carry the necessary information needed to determine conformational entropy at a useful level of precision. The framework introduced here provides a general approach for exploring degeneracies in ensemble determination for different types of experimental data. PMID- 26131694 TI - A Protocol for Housing Mice in an Enriched Environment. AB - Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent studies demonstrate that environmental enrichment decreases adiposity, increases energy expenditure, resists diet induced obesity, and causes cancer remission and inhibition in mice. EE typically consists of larger living space, a variety of 'toys' to interact with, running wheels, and can include a number of other novel environmental changes. All of this fosters a more complex social engagement, cognitive and physical stimulations. Importantly, the toy location and type of toy is changed regularly, which encourages the mice to adapt to a frequently changing and novel environment. Many variables can be manipulated in EE to promote health effects in mice. Thus these approaches are difficult to control and must be properly managed to successfully replicate the associated phenotypes. Therefore, the goal of this video is to demonstrate how EE is properly set up and maintained to assure a complex, challenging, and controlled environment so that other researchers can easily reproduce the protective effects of EE against obesity and cancer. PMID- 26131695 TI - Case 5/2015 Late Outcome of Corrected Aortopulmonary Window in A 23-Year-Old Female Patient Who Underwent Surgery in Childhood. PMID- 26131696 TI - Acute Myocardial Infarction and Severe Prosthetic Dysfunction after Bentall Procedure. PMID- 26131697 TI - Distance Psychotherapy--New Reality. PMID- 26131699 TI - Depression as a Clinical Determinant of Dependence and Low Quality of Life in Elderly Patients with Cardiovascular Disease. AB - BACKGROUND: The aging process promotes a progressive increase in chronic degenerative diseases. The effect of these diseases on the functional capacity has been well recognized. Another health parameter concerns "quality of life related to health". Among the elderly population, cardiovascular diseases stand out due to the epidemiological and clinical impact. Usually, these diseases have been associated with others. This set of problems may compromise both independence and quality of life in elderly patients who seek cardiologic treatment. These health parameters have not been well contemplated by cardiologists. OBJECTIVE: Evaluating, among the elderly population with cardiovascular disease, which are the most relevant clinical determinants regarding dependence and quality of life. METHODS: This group was randomly and consecutively selected and four questionnaires were applied: HAQ, SF-36, PRIME-MD e Mini Mental State. RESULTS: The study included 1,020 elderly patients, 63.3% women. The group had been between 60 and 97 years-old (mean: 75.56 +/- 6.62 years old). 61.4% were independent or mild dependence. The quality of life total score was high (HAQ: 88.66 +/- 2.68). 87.8% of patients had a SF-36 total score > 66. In the multivariate analysis, the association between diagnoses and high degrees of dependence was significant only for previous stroke (p = 0.014), obesity (p < 0.001), lack of physical activity (p = 0.016), osteoarthritis (p < 0.001), cognitive impairment (p < 0.001), and major depression (p < 0.001). Analyzing the quality of life, major depression and physical illness for depression was significantly associated with all domains of the SF-36. CONCLUSION: Among an elderly outpatient cardiology population, dependence and quality of life clinical determinants are not cardiovascular comorbidities, especially the depression. PMID- 26131698 TI - I Brazilian Registry of Heart Failure - Clinical Aspects, Care Quality and Hospitalization Outcomes. AB - BACKGROUND: Heart failure (HF) is one of the leading causes of hospitalization in adults in Brazil. However, most of the available data is limited to unicenter registries. The BREATHE registry is the first to include a large sample of hospitalized patients with decompensated HF from different regions in Brazil. OBJECTIVE: Describe the clinical characteristics, treatment and prognosis of hospitalized patients admitted with acute HF. METHODS: Observational registry study with longitudinal follow-up. The eligibility criteria included patients older than 18 years with a definitive diagnosis of HF, admitted to public or private hospitals. Assessed outcomes included the causes of decompensation, use of medications, care quality indicators, hemodynamic profile and intrahospital events. RESULTS: A total of 1,263 patients (64+/-16 years, 60% women) were included from 51 centers from different regions in Brazil. The most common comorbidities were hypertension (70.8%), dyslipidemia (36.7%) and diabetes (34%). Around 40% of the patients had normal left ventricular systolic function and most were admitted with a wet-warm clinical-hemodynamic profile. Vasodilators and intravenous inotropes were used in less than 15% of the studied cohort. Care quality indicators based on hospital discharge recommendations were reached in less than 65% of the patients. Intrahospital mortality affected 12.6% of all patients included. CONCLUSION: The BREATHE study demonstrated the high intrahospital mortality of patients admitted with acute HF in Brazil, in addition to the low rate of prescription of drugs based on evidence. PMID- 26131700 TI - Assessment of Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease. AB - BACKGROUND: In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase-rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation. OBJECTIVE: This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects. METHODS: Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600-1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNNT), and in AC (RMSNNAC) and DC (RMSNNDC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (alpha < 0.05). RESULTS: Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNNT, RMSNNAC, and RMSNNDC significantly increased linearly with MNN (p < 0.05). In ChD, only RMSNNAC showed significant increase as a function of MNN, whereas RMSNNT and RMSNNDC did not. CONCLUSION: HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence. PMID- 26131701 TI - Post-Acute Coronary Syndrome Alcohol Abuse: Prospective Evaluation in the ERICO Study. AB - BACKGROUND: Some studies have indicated alcohol abuse as one of the contributors to the development of cardiovascular disease, particularly coronary heart disease. However, this relationship is controversial. OBJECTIVE: To investigate the relationship between post-acute coronary syndrome (ACS) alcohol abuse in the Acute Coronary Syndrome Registry Strategy (ERICO Study). METHODS: 146 participants from the ERICO Study answered structured questionnaires and underwent laboratory evaluations at baseline, 30 days and 180 days after ACS. The Alcohol Use Disorders Identification Test (AUDIT) was applied to assess harmful alcohol consumption in the 12 months preceding ACS (30 day-interview) and six months after that. RESULTS: The frequencies of alcohol abuse were 24.7% and 21.1% in the 12 months preceding ACS and six months after that, respectively. The most significant cardiovascular risk factors associated with high-risk for alcohol abuse 30 days after the acute event were: male sex (88.9%), current smoking (52.8%) and hypertension (58.3%). Six months after the acute event, the most significant results were replicated in our logistic regression, for the association between alcohol abuse among younger individuals [35-44 year-old multivariate OR: 38.30 (95% CI: 1.44-1012.56) and 45-54 year-old multivariate OR: 10.10 (95% CI: 1.06-96.46)] and for smokers [current smokers multivariate OR: 51.09 (95% CI: 3.49-748.01) and past smokers multivariate OR: 40.29 (95% CI: 2.37 685.93)]. CONCLUSION: Individuals younger than 54 years and smokers showed a significant relation with harmful alcohol consumption, regardless of the ACS subtype. PMID- 26131702 TI - APOE and LDLR Gene Polymorphisms and Dyslipidemia Tracking. Rio de Janeiro Study. AB - BACKGROUND: Studies show an association between changes in apolipoprotein E (ApoE) and LDLR receptor with the occurrence of dyslipidemia. OBJECTIVES: To investigate the association between polymorphisms of the APOE (epsilon2, epsilon3, epsilon4) and LDLR (A370T) genes with the persistence of abnormal serum lipid levels in young individuals followed up for 17 years in the Rio de Janeiro Study. METHODS: The study included 56 individuals (35 males) who underwent three assessments at different ages: A1 (mean age 13.30 +/- 1.53 years), A2 (22.09 +/- 1.91 years) and A3 (31.23 +/- 1.99 years). Clinical evaluation with measurement of blood pressure (BP) and body mass index (BMI) was conducted at all three assessments. Measurement of waist circumference (WC) and serum lipids, and analysis of genetic polymorphisms by PCR-RFLP were performed at A2 and A3. Based on dyslipidemia tracking, three groups were established: 0 (no abnormal lipid value at A2 and A3), 1 (up to one abnormal lipid value at A2 or A3) and 2 (one or more abnormal lipid values at A2 and A3). RESULTS: Compared with groups 0 and 1, group 2 presented higher mean values of BP, BMI, WC, LDL-c and TG (p < 0.01) and lower mean values of HDL-c (p = 0.001). Across the assessments, all individuals with APOE genotypes epsilon2/epsilon4 and epsilon4/epsilon4 maintained at least one abnormal lipid variable, whereas those with genotype epsilon2/epsilon3 did not show abnormal values (chi2 = 16.848, p = 0.032). For the LDLR genotypes, there was no significant difference among the groups. CONCLUSIONS: APOE gene polymorphisms were associated with dyslipidemia in young individuals followed up longitudinally from childhood. PMID- 26131703 TI - Circulatory and Ventilatory Power: Characterization in Patients with Coronary Artery Disease. AB - BACKGROUND: Circulatory power (CP) and ventilatory power (VP) are indices that have been used for the clinical evaluation of patients with heart failure; however, no study has evaluated these indices in patients with coronary artery disease (CAD) without heart failure. OBJECTIVE: To characterize both indices in patients with CAD compared with healthy controls. METHODS: Eighty-seven men [CAD group = 42 subjects and healthy control group (CG) = 45 subjects] aged 40-65 years were included. Cardiopulmonary exercise testing was performed on a treadmill and the following parameters were measured: 1) peak oxygen consumption (VO2), 2) peak heart rate (HR), 3) peak blood pressure (BP), 4) peak rate pressure product (peak systolic HR x peak BP), 5) peak oxygen pulse (peak VO2/peak HR), 6) oxygen uptake efficiency (OUES), 7) carbon dioxide production efficiency (minute ventilation/carbon dioxide production slope), 8) CP (peak VO2 x peak systolic BP) and 9) VP (peak systolic BP/carbon dioxide production efficiency). RESULTS: The CAD group had significantly lower values for peak VO2 (p < 0.001), peak HR (p < 0.001), peak systolic BP (p < 0.001), peak rate pressure product (p < 0.001), peak oxygen pulse (p = 0.008), OUES (p < 0.001), CP (p < 0.001), and VP (p < 0.001) and significantly higher values for peak diastolic BP (p = 0.004) and carbon dioxide production efficiency (p < 0.001) compared with CG. Stepwise regression analysis showed that CP was influenced by group (R2 = 0.44, p < 0.001) and VP was influenced by both group and number of vessels with stenosis after treatment (interaction effects: R2 = 0.46, p < 0.001). CONCLUSION: The indices CP and VP were lower in men with CAD than healthy controls. PMID- 26131704 TI - Blood Pressure and Hemodynamic Adaptations after a Training Program in Young Individuals with Down Syndrome. AB - BACKGROUND: Cardiovascular diseases affect people worldwide. Individuals with Down Syndrome (DS) have an up to sixteen-time greater risk of mortality from cardiovascular diseases. OBJECTIVE: To evaluate the effects of aerobic and resistance exercises on blood pressure and hemodynamic variables of young individuals with DS. METHODS: A total of 29 young individuals with DS participated in the study. They were divided into two groups: aerobic training (AT) (n = 14), and resistance training (TR) (n = 15). Their mean age was 15.7 +/- 2.82 years. The training program lasted 12 weeks, and had a frequency of three times a week for AT and twice a week for RT. AT was performed in treadmill/ bicycle ergometer, at an intensity between 50%-70% of the HR reserve. RT comprised nine exercises with three sets of 12 repetition-maximum. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and hemodynamic variables were assessed beat-to-beat using the Finometer device before/after the training program. Descriptive analysis, the Shapiro-Wilk test to check the normality of data, and the two-way ANOVA for repeated measures were used to compare pre- and post-training variables. The Pearson's correlation coefficient was calculated to correlate hemodynamic variables. The SPSS version 18.0 was used with the significance level set at p < 0.05. RESULTS: After twelve weeks of aerobic and/or resistance training, significant reductions in variables SBP, DBP and MBP were observed. CONCLUSION: This study suggests a chronic hypotensive effect of moderate aerobic and resistance exercises on young individuals with DS. PMID- 26131705 TI - Heart Rate Variability Correlates to Functional Aerobic Impairment in Hemodialysis Patients. AB - BACKGROUND: Autonomic dysfunction (AD) is highly prevalent in hemodialysis (HD) patients and has been implicated in their increased risk of cardiovascular mortality. OBJECTIVE: To correlate heart rate variability (HRV) during exercise treadmill test (ETT) with the values obtained when measuring functional aerobic impairment (FAI) in HD patients and controls. METHODS: Cross-sectional study involving HD patients and a control group. Clinical examination, blood sampling, transthoracic echocardiogram, 24-hour Holter, and ETT were performed. A symptom limited ramp treadmill protocol with active recovery was employed. Heart rate variability was evaluated in time domain at exercise and recovery periods. RESULTS: Forty-one HD patients and 41 controls concluded the study. HD patients had higher FAI and lower HRV than controls (p<0.001 for both). A correlation was found between exercise HRV (SDNN) and FAI in both groups. This association was independent of age, sex, smoking, body mass index, diabetes, and clonidine or beta-blocker use, but not of hemoglobin levels. CONCLUSION: No association was found between FAI and HRV on 24-hour Holter or at the recovery period of ETT. Of note, exercise HRV was inversely correlated with FAI in HD patients and controls. PMID- 26131706 TI - Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure. AB - In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis. PMID- 26131707 TI - An Issue Waiting to be Clarified: Effects of the QT Prolonging Drugs on Tp-e Interval. PMID- 26131708 TI - Theoretical Study on Molecules of Interstellar Interest. II. Radical Cation of Compact Polycyclic Aromatic Hydrocarbons. AB - Radical cations of polycyclic aromatic hydrocarbons have been postulated to be molecular carriers of diffuse spectroscopic features observed in the interstellar medium. Several important observations made by stellar and laboratory spectroscopists motivated us to undertake a detailed theoretical study attempting to validate the recorded data. In continuation of our work on this subject, we here focus on a detailed theoretical study of the doublet ground (X) and low lying excited (A, B, and C) electronic states of the radical cation of phenanthrene, pyrene, and acenaphthene molecule. A multistate and multimode theoretical model in a diabatic electronic basis is developed here through extensive ab initio quantum chemistry calculations. Employing this model, first principles nuclear dynamics calculations are carried out to unravel the spectral assignment, time-dependent dynamics, and photostability of the mentioned electronic states of the radical cations. The theoretical results compare well with the observed experimental data. PMID- 26131709 TI - Quantification of liver fibrosis via second harmonic imaging of the Glisson's capsule from liver surface. AB - Liver surface is covered by a collagenous layer called the Glisson's capsule. The structure of the Glisson's capsule is barely seen in the biopsy samples for histology assessment, thus the changes of the collagen network from the Glisson's capsule during the liver disease progression are not well studied. In this report, we investigated whether non-linear optical imaging of the Glisson's capsule at liver surface would yield sufficient information to allow quantitative staging of liver fibrosis. In contrast to conventional tissue sections whereby tissues are cut perpendicular to the liver surface and interior information from the liver biopsy samples were used, we have established a capsule index based on significant parameters extracted from the second harmonic generation (SHG) microscopy images of capsule collagen from anterior surface of rat livers. Thioacetamide (TAA) induced liver fibrosis animal models was used in this study. The capsule index is capable of differentiating different fibrosis stages, with area under receiver operating characteristics curve (AUC) up to 0.91, making it possible to quantitatively stage liver fibrosis via liver surface imaging potentially with endomicroscopy. PMID- 26131711 TI - Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and the DNA Damage Response in the Fission Yeast S.pombe. AB - The activity of Cdc2 (CDK1) kinase, which coordinates cell cycle progression and DNA break repair, is blocked upon its phosphorylation at tyrosine 15 (Y15) by Wee1 kinase in the presence of DNA damage. How Cdc2 can support DNA repair whilst being inactivated by the DNA damage checkpoint remains to be explained. Human CDK1 is phosphorylated by Myt1 kinase at threonine 14 (T14) close to its ATP binding site before being modified at threonine 161 (T167Sp) in its T-loop by the CDK-activating kinase (CAK). While modification of T161 promotes association with the cyclin partner, phosphorylation of T14 inhibits the CDK1-cyclin complex. This inhibition is further enforced by the modification of Y15 by Wee1 in the presence of DNA lesions. In S.pombe, the dominant inhibition of Cdc2 is provided by the phosphorylation of Y15 and only a small amount of Cdc2 is modified at T14 when cells are in S phase. Unlike human cells, both inhibitory modifications are executed by Wee1. Using the novel IEFPT technology, which combines isoelectric focusing (IEF) with Phos-tag SDS electrophoresis (PT), we report here that S.pombe Cdc2 kinase exists in seven forms. While five forms are phosphorylated, two species are not. Four phospho-forms associate with cyclin B (Cdc13) of which only two are modified at Y15 by Wee1. Interestingly, only one Y15-modified species carries also the T14 modification. The fifth phospho-form has a low affinity for cyclin B and is neither Y15 nor T14 modified. The two unphosphorylated forms may contribute directly to the DNA damage response as only they associate with the DNA damage checkpoint kinase Chk1. Interestingly, cyclin B is also present in the unphosphorylated pool. We also show that the G146D mutation in Cdc2.1w, which renders Cdc2 insensitive to Wee1 inhibition, is aberrantly modified in a Wee1-dependent manner. In conclusion, our work adds support to the idea that two distinct Cdc2 pools regulate cell cycle progression and the response to DNA damage. PMID- 26131712 TI - Branched Polyhedral Oligomeric Silsesquioxane Nanoparticles Prepared via Strain Promoted 1,3-Dipolar Cycloadditions. AB - Conjugation of small organic molecules and polymers to polyhedral oligosilsesquioxane (POSS) cores results in novel hybrid materials with unique physical characteristics. We report here an approach in which star-shaped organic inorganic scaffolds bearing eight cyclooctyne moieties can be rapidly functionalized via strain-promoted azide-alkyne cycloaddition (SPAAC) to synthesize a series of nearly monodisperse branched core-shell nanoparticles with hydrophobic POSS cores and hydrophilic arms. We established that SPAAC is a robust method for POSS core octafunctionalization with the reaction rate constant of 1.9 * 10(-2) M(-1) s(-1). Functionalization with poly(ethylene glycol) (PEG) azide, fluorescein azide, and unprotected lactose azide gave conjugates which represent different classes of compounds: polymer conjugates, fluorescent dots, and bioconjugates. These resulting hybrid compounds were preliminarily tested for their ability to self-assemble in solution and at the air-water interface. We observed the formation of robust smooth Langmuir monolayers with diverse morphologies. We found that polar lactose moieties are completely submerged into the subphase whereas the relatively hydrophobic fluorescein arms had extended conformation at the interface, and PEG arms were partially submerged. Finally, we observed the formation of stable micelles with sizes between 70 and 160 nm in aqueous solutions with size and morphology of the structures dependent on the molecular weight and the type of the peripheral hydrophilic moieties. PMID- 26131714 TI - The Role of Personality and Social Support in Health-Related Quality of Life in Chronic Kidney Disease Patients. AB - BACKGROUND: Chronic kidney disease (CKD) is commonly associated with various negative health outcomes. The aim of this study was to examine the influence of personality and social support on health-related quality of life in patients with chronic kidney disease. Health-related quality of life (HRQoL) is the quality of life studied in relation to health, and it provides important information of patients' coping with their health issues. METHOD: Participants comprised of 200 patients experiencing various stages of chronic kidney disease. All participants completed the Short-Form 36 (SF-36), Big Five Inventory (BFI) and the Medical Outcomes Study (MOS) Social Support questionnaires. RESULTS: Participants consisted of 108 males (54.0%) and 92 females (46.0%) with the mean age of 59.3 years (SD 14.5). Results showed that higher levels of extraversion and lower perceived affectionate social support were associated with higher physical HRQoL, whereas higher levels of neuroticism were associated with poorer mental HRQoL. CONCLUSION: The current study found that certain personality traits, namely extraversion and neuroticism, were found to be associated with HRQoL. In addition, affectionate social support was also associated with higher HRQoL. Therefore, special attention should be paid to the personality of CKD patients, as well as the type of social support that they have, in planning interventions to improve their health outcomes. PMID- 26131715 TI - EICOSAPENTAENOIC ACID ENHANCES HEATSTROKE-IMPAIRED INTESTINAL EPITHELIAL BARRIER FUNCTION IN RATS. AB - OBJECTIVE: Dysfunction of the intestinal barrier plays an important role in the pathological process of heatstroke. Omega-3 (or n-3) polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), help protect the intestinal mucosal barrier. This study assessed if pretreating rats with EPA or DHA could alleviate heat stress-induced damage to the intestinal barrier caused by experimental heatstroke. METHODS: Male Wistar rats were pregavaged with either EPA, DHA, corn oil, or normal saline (all 1 g/kg) for 21 days before the heatstroke experiment (control rats were not exposed to heat). Experimental rats were exposed to an ambient temperature of 37 degrees C and 60% humidity to induce heatstroke, and then they were allowed to recover at room temperature after rapid cooling. Survival time of rats was monitored after heatstroke. Horseradish peroxidase flux from the gut lumen and the level of plasma D-lactate were measured to analyze intestinal permeability at 6 h after heatstroke. Plasma endotoxin levels were determined using a limulus amoebocyte lysate assay. Expressions of the tight junction (TJ) proteins occludin and ZO-1 were analyzed by Western blot and localized by immunofluorescence microscopy. Tight junction protein morphology was observed by transmission electron microscopy. Fatty acids of ileal mucosa were analyzed using gas chromatography mass selective detector. RESULTS: Eicosapentaenoic acid significantly increased survival time after heatstroke. Eicosapentaenoic acid significantly decreased intestinal permeability and plasma endotoxin levels. Eicosapentaenoic acid effectively attenuated the heatstroke-induced disruption of the intestinal structure and improved the histology score, whereas DHA was less effective, and corn oil was ineffective. Pretreatment with EPA also increased expression of occludin and ZO-1 to effectively prevent TJ disruption. Eicosapentaenoic acid pretreatment enriched itself in the membrane of intestinal cells. CONCLUSIONS: Our results indicate that EPA pretreatment is more effective than DHA pretreatment in attenuating heat-induced intestinal dysfunction and preventing TJ damage. Enhanced expression of TJ proteins that support the epithelial barrier integrity may be important for maintaining a functional intestinal barrier during heatstroke. PMID- 26131713 TI - GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo. AB - We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC. PMID- 26131716 TI - Neuropeptide Y Stimulates Proliferation and Migration of Vascular Smooth Muscle Cells from Pregnancy Hypertensive Rats via Y1 and Y5 Receptors. AB - The increased proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in pathophysiological remodeling of arteries during hypertension in pregnancy. However, the mechanisms involved in this process remain unclear. We hypothesized that Neuropeptide Y (NPY), which is a potent mitogenic peptide, participates in modulating proliferation and migration of VSMCs during hypertension in pregnancy. Using pregnant hypertensive rats, induced by intraperitoneal injection of L-nitro-arginine methylester (L-NAME), the plasma concentration of NPY was detected. Open angle, which reflects the non-uniform remodeling with high sensitivity, was used to detect the pathophysiological vascular remodeling in vivo. The results revealed that NPY concentration and artery open angle were both significantly increased in rats with hypertension in pregnant. The underlying mechanism of elevated NPY on vascular remodeling were further analyzed by using cultured VSMCs in vitro. In cultured VSMCs, NPY most effectively stimulated the migration and proliferation of VSMCs at 10-6 mol/L, similar to the plasma concentration in L-NAME hypertension in pregnant rats. NPY up-regulated the expressions of both Y1 and Y5 receptors, increased the phosphorylations of STAT3 on Tyr705 and Ser727 residues, and induced the expression of c-Fos. The NPY-induced VSMCs proliferation was reduced by Y5 receptor antagonist, and fully blocked by combinations with other antagonist, such as Y2+Y5, Y1+Y5, and Y1+Y2+Y5. In contrast, the NPY-induced VSMC migration was blocked by either Y receptor antagonist or any combination of Y receptor antagonists. These results suggest that the elevated plasma concentration of NPY during hypertension in pregnancy may induce VSMC proliferation mainly via Y5 receptor, which subsequently modulate STAT3 and c-Fos signaling pathways to result in the vascular remodeling. These results also suggest that NPY mainly acts on VSMCs in vitro via Y1, Y5 receptors and in vascular tissues in vivo via Y5 receptor. PMID- 26131717 TI - Acoustic Radiation Force Impulse Elastography for the Non-Invasive Evaluation of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review & Meta-Analysis. AB - BACKGROUND: In order to better monitor non-alcoholic fatty liver disease (NAFLD) patients at higher risk for HCC, there is a need for non-invasive diagnostic approaches to screen for the presence of advanced fibrosis in these patients. The aim of this systematic review and meta-analysis will be to evaluate the diagnostic efficacy of ARFI elastography in detecting hepatic fibrosis in NAFLD patients. METHODS: Relevant studies were identified from systematic searches of several major electronic databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials). The primary outcomes were the summary sensitivity, summary specificity, the diagnostic odds ratio, and the summary receiver operating characteristic curve (SROC) of ARFI elastography in detecting significant fibrosis (defined as 4>F>=2) in NAFLD patients. Study quality was assessed using the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Review (QUADAS-2). RESULTS: The summary sensitivity and specificity of ARFI in detecting significant fibrosis were 80.2% (95% confidence interval (CI): 0.758-0.842; p = 0.0000) and 85.2% (95% CI: 0.808-0.890), p = 0.1617), respectively. The pooled diagnostic odds ratio of ARFI in detecting significant fibrosis was 30.13 (95% CI: 12.08-75; chi-squared = 14.59, p = 0.0237). The area under the SROC curve (AUC) was 0.898 (standard error (SE): 0.031) with a Q* index of 0.830 (SE: 0.033). CONCLUSIONS: ARFI elastography appears to be modestly accurate in detecting significant fibrosis in NAFLD patients. Future studies in this field should provide head-to-head comparisons of ARFI elastography versus other elastographic imaging modalities in NAFLD patients. PMID- 26131718 TI - Characterization of Anti-Citrinin Specific ScFvs Selected from Non-Immunized Mouse Splenocytes by Eukaryotic Ribosome Display. AB - Single chain variable fragments (scFvs) against citrinin (CIT) were selected from a scFv library constructed from the splenocytes of non-immunized mice by an improved eukaryotic ribosome display technology in this study. Bovine serum albumin (BSA)/ CIT-BSA and ovalbumin (OVA)/ CIT-OVA were used as the antigens to select specific anti-CIT scFvs. Eukaryotic in situ RT-PCR method was used to recover the selected mRNA after every affinity selection. After six rounds of ribosome display, expression vector pTIG-TRX carrying specific scFv DNAs were constructed and transformed into Escherichia coli BL21 (DE3) for protein expression. Thirteen positive clones were selected out of which three (designated 23, 68 and 109) showed high binding activity and specificity to CIT by indirect ELISA, while no clone showed binding activity with carrier proteins. The three scFvs showed high specificity to CIT and the cross reactivity with other mycotoxins was below 0.01% as determined by indirect competitive ELISA. These specific scFvs offer a potential novel immunoassay method for CIT residues. This study confirmed the effectiveness of the improved eukaryotic ribosome display system and could be used as a reference for the selection of scFvs specific to other small molecules using ribosome display. PMID- 26131721 TI - Correction: Detecting Fragmentation Extinction Thresholds for Forest Understory Plant Species in Peninsular Spain. PMID- 26131719 TI - TopBP1 Governs Hematopoietic Stem/Progenitor Cells Survival in Zebrafish Definitive Hematopoiesis. AB - In vertebrate definitive hematopoiesis, nascent hematopoietic stem/progenitor cells (HSPCs) migrate to and reside in proliferative hematopoietic microenvironment for transitory expansion. In this process, well-established DNA damage response pathways are vital to resolve the replication stress, which is deleterious for genome stability and cell survival. However, the detailed mechanism on the response and repair of the replication stress-induced DNA damage during hematopoietic progenitor expansion remains elusive. Here we report that a novel zebrafish mutantcas003 with nonsense mutation in topbp1 gene encoding topoisomerase II beta binding protein 1 (TopBP1) exhibits severe definitive hematopoiesis failure. Homozygous topbp1cas003 mutants manifest reduced number of HSPCs during definitive hematopoietic cell expansion, without affecting the formation and migration of HSPCs. Moreover, HSPCs in the caudal hematopoietic tissue (an equivalent of the fetal liver in mammals) in topbp1cas003 mutant embryos are more sensitive to hydroxyurea (HU) treatment. Mechanistically, subcellular mislocalization of TopBP1cas003 protein results in ATR/Chk1 activation failure and DNA damage accumulation in HSPCs, and eventually induces the p53-dependent apoptosis of HSPCs. Collectively, this study demonstrates a novel and vital role of TopBP1 in the maintenance of HSPCs genome integrity and survival during hematopoietic progenitor expansion. PMID- 26131720 TI - Bioinformatic Analysis of Chlamydia trachomatis Polymorphic Membrane Proteins PmpE, PmpF, PmpG and PmpH as Potential Vaccine Antigens. AB - Chlamydia trachomatis is the most important infectious cause of infertility in women with important implications in public health and for which a vaccine is urgently needed. Recent immunoproteomic vaccine studies found that four polymorphic membrane proteins (PmpE, PmpF, PmpG and PmpH) are immunodominant, recognized by various MHC class II haplotypes and protective in mouse models. In the present study, we aimed to evaluate genetic and protein features of Pmps (focusing on the N-terminal 600 amino acids where MHC class II epitopes were mapped) in order to understand antigen variation that may emerge following vaccine induced immune selection. We used several bioinformatics platforms to study: i) Pmps' phylogeny and genetic polymorphism; ii) the location and distribution of protein features (GGA(I, L)/FxxN motifs and cysteine residues) that may impact pathogen-host interactions and protein conformation; and iii) the existence of phase variation mechanisms that may impact Pmps' expression. We used a well-characterized collection of 53 fully-sequenced strains that represent the C. trachomatis serovars associated with the three disease groups: ocular (N=8), epithelial-genital (N=25) and lymphogranuloma venereum (LGV) (N=20). We observed that PmpF and PmpE are highly polymorphic between LGV and epithelial-genital strains, and also within populations of the latter. We also found heterogeneous representation among strains for GGA(I, L)/FxxN motifs and cysteine residues, suggesting possible alterations in adhesion properties, tissue specificity and immunogenicity. PmpG and, to a lesser extent, PmpH revealed low polymorphism and high conservation of protein features among the genital strains (including the LGV group). Uniquely among the four Pmps, pmpG has regulatory sequences suggestive of phase variation. In aggregate, the results suggest that PmpG may be the lead vaccine candidate because of sequence conservation but may need to be paired with another protective antigen (like PmpH) in order to prevent immune selection of phase variants. PMID- 26131722 TI - Characterising the Transmission Dynamics of Acinetobacter baumannii in Intensive Care Units Using Hidden Markov Models. AB - Little is known about the transmission dynamics of Acinetobacter baumannii in hospitals, despite such information being critical for designing effective infection control measures. In the absence of comprehensive epidemiological data, mathematical modelling is an attractive approach to understanding transmission process. The statistical challenge in estimating transmission parameters from infection data arises from the fact that most patients are colonised asymptomatically and therefore the transmission process is not fully observed. Hidden Markov models (HMMs) can overcome this problem. We developed a continuous time structured HMM to characterise the transmission dynamics, and to quantify the relative importance of different acquisition sources of A. baumannii in intensive care units (ICUs) in three hospitals in Melbourne, Australia. The hidden states were the total number of patients colonised with A. baumannii (both detected and undetected). The model input was monthly incidence data of the number of detected colonised patients (observations). A Bayesian framework with Markov chain Monte Carlo algorithm was used for parameter estimations. We estimated that 96-98% of acquisition in Hospital 1 and 3 was due to cross transmission between patients; whereas most colonisation in Hospital 2 was due to other sources (sporadic acquisition). On average, it takes 20 and 31 days for each susceptible individual in Hospital 1 and Hospital 3 to become colonised as a result of cross-transmission, respectively; whereas it takes 17 days to observe one new colonisation from sporadic acquisition in Hospital 2. The basic reproduction ratio (R0) for Hospital 1, 2 and 3 was 1.5, 0.02 and 1.6, respectively. Our study is the first to characterise the transmission dynamics of A. baumannii using mathematical modelling. We showed that HMMs can be applied to sparse hospital infection data to estimate transmission parameters despite unobserved events and imperfect detection of the organism. Our results highlight the need to optimise infection control in ICUs. PMID- 26131723 TI - On the Frontline: Tracking Ocean Acidification in an Alaskan Shellfish Hatchery. AB - The invasion of anthropogenic carbon dioxide (CO2) into the ocean is shifting the marine carbonate system such that saturation states of calcium carbonate (CaCO3) minerals are decreasing, and this is having a detrimental impact on early life stages of select shellfish species. The global, secular decrease in CaCO3 saturation states is occurring on top of a backdrop of large natural variability in coastal settings; progressively shifting the envelope of variability and leading to longer and more frequent exposure to adverse conditions. This is a great concern in the State of Alaska, a high-latitude setting vulnerable to rapid changes in the marine carbonate system, where an emerging shellfish industry plans major growth over the coming decades. Currently, the Alutiiq Pride Shellfish Hatchery (APSH) in Seward, Alaska is the only hatchery in the state, and produces many shellfish species with early life stages known to be sensitive to low CaCO3 saturation states. Here we present the first land-based OA measurements made in an Alaskan shellfish hatchery, and detail the trends in the saturation state of aragonite (Omegaarag), the more soluble form of CaCO3, over a 10-month period in the APSH seawater supply. These data indicate the largest changes are on the seasonal time scale, with extended periods of sub-optimal Omegaarag levels (Omegaarag < 1.5) in winter and autumn associated with elevated water column respiration and short-lived runoff events, respectively. The data pinpoint a 5-month window of reprieve with favorable Omegaarag conditions above the sub-optimal Omegaarag threshold, which under predicted upper-bound CO2 emissions trajectories is estimated to close by 2040. To date, many species in production at APSH remain untested in their response to OA, and the data presented here establish the current conditions at APSH as well as provide a framework for hatchery-based measurements in Alaska. The current and expected conditions seen at APSH are essential to consider for this developing Alaskan industry. PMID- 26131724 TI - Mood-Reactive Self-Esteem and Depression Vulnerability: Person-Specific Symptom Dynamics via Smart Phone Assessment. AB - Cognitive theories of depression suggest that mood-reactive self-esteem, a pattern of cognitive reactivity where low self-esteem is temporally dependent on levels of sadness, represents vulnerability for depression. Few studies have directly tested this hypothesis, particularly using intensive data collection methods (i.e., experience sampling) required to capture the temporal dynamics of sadness and self-esteem as they unfold naturally, over time. In this study we used participants' smartphones to collect multiple daily ratings of sadness and self-esteem over three weeks, in the real world. We then applied dynamic factor modeling to explore theoretically driven hypotheses about the temporal dependency of self-esteem on sadness (i.e., mood-reactive self-esteem) and its relationship to indices of depression vulnerability both contemporaneously (e.g., rumination, sad mood persistence) and prospectively (e.g., future symptomatology). In sum, individuals who demonstrated mood-reactive self-esteem reported higher levels of rumination at baseline, more persistent sad mood over three weeks, and increased depression symptoms at the end of three weeks above and beyond a trait-like index of self-esteem. The integration of smartphone assessment and person-specific analytics employed in this study offers an exiting new avenue to advance the study and treatment of depression. PMID- 26131725 TI - Design of Protein-Peptide Interaction Modules for Assembling Supramolecular Structures in Vivo and in Vitro. AB - Synthetic biology and protein origami both require protein building blocks that behave in a reliable, predictable fashion. In particular, we require protein interaction modules with known specificity and affinity. Here, we describe three designed TRAP (Tetratricopeptide Repeat Affinity Protein)-peptide interaction pairs that are functional in vivo. We show that each TRAP binds to its cognate peptide and exhibits low cross-reactivity with the peptides bound by the other TRAPs. In addition, we demonstrate that the TRAP-peptide interactions are functional in many cellular contexts. In extensions of these designs, we show that the binding affinity of a TRAP-peptide pair can be systematically varied. The TRAP-peptide pairs we present thus represent a powerful set of new building blocks that are suitable for a variety of applications. PMID- 26131726 TI - Depression and Its Comorbid Conditions More Serious in Women than in Men in the United States. AB - BACKGROUND: Depression is a major public health problem by itself and for its comorbid conditions. We aimed to determine gender differences in the prevalence of depression and how depression is related to comorbid conditions and metabolic biomarkers. METHODS: This study included men (n=986) and women (n=1,280) aged 20 79 years who were included in the 2007-2010 National Health and Nutrition Examination Survey. Depression was assessed with the Patient Health Questionnaire (PHQ-9). The associations between depression (PHQ-9 score >=10), self-reported comorbid conditions, and metabolic biomarkers of comorbid conditions were determined by multivariable logistic regressions adjusting for potential confounders. RESULTS: The prevalence of depression in men and women were 7.9% and 12.1%, respectively (p<0.01). The odds ratios (OR) of various comorbid conditions (asthma, arthritis, gout, coronary heart disease, heart attack, stroke, diabetes mellitus, thyroid problem, and metabolic syndrome) by the status of depression were significantly higher in women. High C-reactive protein (CRP) was a significant predictor of depression in men (OR 2.02, 95% confidence interval [CI] 1.11-3.67) in unadjusted model. In women, high fasting blood glucose, high glycohemoglobin, and high CRP were significant predictors of depression (OR 1.20, 95% CI 1.28-3.01; OR 2.44, 95% CI 1.21-4.92; OR 1.44, 95% CI 1.01-2.06; OR 1.79, 95% CI 0.19-2.67, respectively) after controlling for age, education, race/ethnicity, marital status, ratio of family income to poverty, and physical activity. CONCLUSIONS: Women had higher prevalence of depression and higher number of significant associations between socioeconomic status, comorbid conditions, and metabolic risk factors by the status of depression than men. Public health attentions are needed to improve women's mental health. PMID- 26131728 TI - Abstracts - Late Breaking. PMID- 26131729 TI - Effects of Recipient Age and Diagnosis on Health-related Quality-of-Life Benefit of Lung Transplantation. AB - RATIONALE: The average age of lung transplant recipients is increasing, and the mix of recipient indications for transplantation is changing. OBJECTIVES: To determine whether the health-related quality-of-life (HRQL) benefit of lung transplantation differs by recipient age and diagnosis. METHODS: In this prospective cohort study, we obtained serial HRQL measurements in adults with advanced lung disease who subsequently underwent lung transplantation (2004 2012). HRQL assessments included the St. George's Respiratory Questionnaire, 36 Item Short-Form Health Survey (SF-36), EQ-5D, Standard Gamble, and Visual Analog Scale for current health. We used linear mixed effects models for associations between age or diagnosis and changes in HRQL with transplantation. To address potential survivorship bias, we fitted Markov models to the distribution of discrete post-transplant health states (HRQL better than pretransplant, not better, or dead) and estimated quality-adjusted life-years post-transplant. MEASUREMENTS AND MAIN RESULTS: A total of 430 subjects were listed, 387 were transplanted, and 326 provided both pretransplant and post-transplant data. Transplantation conferred large improvements in all HRQL measures: St. George's change of -47 units (95% confidence interval, -48 to -44), 36-Item Short-Form Health Survey physical component summary score of 17.7 (16.5-18.9), EQ-5D of 0.27 (0.24-0.30), Standard Gamble of 0.48 (0.44-0.51), and Visual Analog of 44 (42 47). Age was not associated with meaningful differences in the HRQL benefits of transplantation. There was less HRQL benefit in interstitial lung disease than in cystic fibrosis. CONCLUSIONS: Lung transplantation confers large HRQL benefits, which vary by recipient diagnosis, but do not differ substantially in older recipients. PMID- 26131730 TI - A role for the thermal environment in defining co-stimulation requirements for CD4(+) T cell activation. AB - Maintenance of normal core body temperature is vigorously defended by long conserved, neurovascular homeostatic mechanisms that assist in heat dissipation during prolonged, heat generating exercise or exposure to warm environments. Moreover, during febrile episodes, body temperature can be significantly elevated for at least several hours at a time. Thus, as blood cells circulate throughout the body, physiologically relevant variations in surrounding tissue temperature can occur; moreover, shifts in core temperature occur during daily circadian cycles. This study has addressed the fundamental question of whether the threshold of stimulation needed to activate lymphocytes is influenced by temperature increases associated with physiologically relevant increases in temperature. We report that the need for co-stimulation of CD4+ T cells via CD28 ligation for the production of IL-2 is significantly reduced when cells are exposed to fever-range temperature. Moreover, even in the presence of sufficient CD28 ligation, provision of extra heat further increases IL-2 production. Additional in vivo and in vitro data (using both thermal and chemical modulation of membrane fluidity) support the hypothesis that the mechanism by which temperature modulates co-stimulation is linked to increases in membrane fluidity and membrane macromolecular clustering in the plasma membrane. Thermally regulated changes in plasma membrane organization in response to physiological increases in temperature may assist in the geographical control of lymphocyte activation, i.e., stimulating activation in lymph nodes rather than in cooler surface regions, and further, may temporarily and reversibly enable CD4+ T cells to become more quickly and easily activated during times of infection during fever. PMID- 26131731 TI - Conserved Telomere Length in Human Ectopic Thyroids: An Argument Against Premature Differentiation Causing Arrested Migration. AB - BACKGROUND: In humans, the cause of arrested migration of the median thyroid anlage resulting in an ectopic sublingual gland is unknown. These ectopic glands have a normal follicular architecture but their thyrotropin-induced growth is insufficient, leading to congenital hypothyroidism in the vast majority of affected subjects. We hypothesized that arrested migration is due to premature differentiation [reflected by decreased telomere length (TL)], as observed in neural tube defects in mice. METHODS: Absolute TL and telomerase reverse transcriptase (hTERT) expression was measured in four ectopic and six orthotopic thyroids. TL was measured by quantitative polymerase chain reaction of genomic DNA, whereas hTERT expression was measured by quantitative polymerase chain reaction of total RNA. RESULTS: The mean+/-standard deviation TL (in kilobases per diploid genome) was 140.45+/-40.07 in ectopic and 97.50+/-30.48 in orthotopic thyroids (p=0.12). Expression of hTERT was quiescent in both ectopic and orthotopic thyroids. CONCLUSIONS: Compared with orthotopic thyroids, TL shortening is not observed in ectopic thyroid tissues and, consequently, no compensatory hTERT expression was measured. This makes premature differentiation an unlikely cause of arrested migration and it suggests, indirectly, that ectopic thyroids are not at higher risk of cancer than orthotopic thyroids. PMID- 26131732 TI - Five water-soluble zwitterionic copper(II)-carboxylate polymers: role of dipyridyl coligands in enhancing the DNA-binding, cleaving and anticancer activities. AB - Five water-soluble zwitterionic copper-carboxylate polymers were prepared from the reaction of N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide (H3CmdcpBr) with Cu(NO3)2 in the presence of NaOH by modulating the temperature, solvent and ancillary dipyridyl ligands. These complexes include a 1D ladder-shaped polymer {[Cu3(Cmdcp)2(OH)2(H2O)2].H2O}n () formed in H2O at room temperature, and a 2D network polymer {[Cu(Cmdcp) (H2O)2].2H2O}n () isolated in H2O at 135 degrees C. At 100 degrees C in H2O/DMF, the same reaction in the presence of an additional 2,2'-bipyridine (bipy) gave a 2D zwitterionic complex {[Cu(Cmdcp)(bipy)].3H2O}n () together with a 1D double-stranded polymer {[Cu(Cmdcp)(H2O)2].H2O}n () as a minor product. The replacement of bipy with phenanthroline (phen) afforded a 1D zigzag polymer chain {[Cu(Cmdcp)(phen)(H2O)]2.9H2O}5 (). All these complexes were characterized by IR, elemental analyses and single crystal X-ray crystallography. Agarose gel electrophoresis (GE) and ethidium bromide (EB) displacement experiments indicated that complex exhibited the highest pBR322 DNA cleaving ability with the catalytic efficiency (kmax/KM) of 14.80 h(-1) mM(-1) and the highest binding affinity toward calf-thymus DNA. The MTT assay indicated that complex showed significant inhibitory activity toward the proliferation of several tumor cells. Its IC50 value was at micromolar level and lower than those of cisplatin and complexes , especially toward resistant lung adenocarcinoma cell A549. PMID- 26131734 TI - Dermatologic Features of ADA2 Deficiency in Cutaneous Polyarteritis Nodosa. AB - IMPORTANCE: Mutations in the CERC1 gene associated with deficiency in the ADA2 protein (DADA2) have been implicated in the pathogenesis of cutaneous polyarteritis nodosa (cPAN) and early-onset vasculopathy. DADA2 is not only limited to cPAN and vasculopathy but also includes immunodeficiency that affects several cellular compartments, including B cells; however, some patients appear to have a more indolent, skin-limited disease. OBSERVATIONS: In this report, we describe 2 white siblings (female and male) with a history of cPAN with DADA2 as a result of novel compound heterozygous mutations inherited in trans in the CECR1 gene (c.37_39del [p.K13del] and c.1159C>A [p.N328K]). The onset of disease was earlier in the female sibling than the male sibling although both were diagnosed as having cPAN in early childhood. The disease is associated with a more significant immunodeficiency and other systemic symptoms in the female than the male sibling. CONCLUSIONS AND RELEVANCE: These findings suggest a genetic cause of cPAN in some patients. Therefore, DADA2 should be considered in patients with cPAN, specifically in those whose conditions are diagnosed at an early age, regardless of their ethnicity, presence or absence of systemic symptoms, or a family history of the disease. PMID- 26131735 TI - All Eyes on Egypt: Islam and the Medical Use of Dead Bodies Amidst Cairo's Political Unrest. AB - Using dead bodies for medical purposes has long been considered taboo in Egypt. Public health campaigns, physicians' pleas, and the urgings of religious scholars all failed to alter public opinion regarding the donation of dead bodies either for instructional material or for therapeutic treatments. Yet in 2011, amid revolutionary turmoil in Egypt, a campaign was launched for people to donate their eyes upon death; this time, people readily signed up to be donors. Focusing on mass eye trauma that occurred in Egypt amid the political uprisings of 2011, I raise questions about when and why Islam can explain people's attitudes and behaviors, particularly toward death and medicine. The case of mass eye trauma in Egypt and citizens' reformulations of questions once jealously controlled by state-aligned doctors, politicians, and religious scholars unsettles the boundaries between 'religion' and 'secularism' in medical practice. [Formula: see text]. PMID- 26131738 TI - Error in Figure Caption. Mortality in Mental Disorders and Global Disease Burden Implications: A Systematic Review and Meta-analysis. PMID- 26131739 TI - Incorrect Sentences in Abstract. Transdiagnostic Factors and Mediation of the Relationship Between Perceived Racial Discrimination and Mental Disorders. PMID- 26131740 TI - DNA Ligases I and III Support Nucleotide Excision Repair in DT40 Cells with Similar Efficiency. AB - In eukaryotic cells helix-distorting DNA lesions like cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidone photoproducts (6-4 PPs) are efficiently removed by nucleotide excision repair (NER). NER is a multistep process where in the end, subsequent to replication over the gap, the remaining nick is sealed by a DNA ligase. Lig1 has been implicated as the major DNA ligase in NER. Recently, Lig3 has been implicated as a component of a NER subpathway that operates in dividing cells, but which becomes particularly important in nondividing cells. Here, we use DT40 cells and powerful gene targeting approaches for generating DNA ligase mutants to examine the involvement and contribution of Lig1 and Lig3 in NER using cell survival measured by colony formation, and repair kinetics of CPD by immunofluorescence microscopy and immuno-slot-blotting. Our results demonstrate an impressive and previously undocumented potential of Lig3 to substitute for Lig1 in removing helix-distorting DNA lesions by NER in proliferating cells. We show for the first time in a clean genetic background a functional redundancy in NER between Lig1 and Lig3, which appears to be cell cycle independent and which is likely to contribute to the stability of vertebrate genomes. PMID- 26131741 TI - Co-selection and replacement of resistance alleles to Lysinibacillus sphaericus in a Culex quinquefasciatus colony. AB - The Cqm1 alpha-glucosidase, expressed within the midgut of Culex quinquefasciatus mosquito larvae, is the receptor for the Binary toxin (Bin) from the entomopathogen Lysinibacillus sphaericus. Mutations of the Cqm1 alpha-glucosidase gene cause high resistance levels to this bacterium in both field and laboratory populations, and a previously described allele, cqm1REC, was found to be associated with a laboratory-resistant colony (R2362). This study described the identification of a novel resistance allele, cqm1REC-2, that was co-selected with cqm1REC within the R2362 colony. The two alleles display distinct mutations but both generate premature stop codons that prevent the expression of midgut-bound Cqm1 proteins. Using a PCR-based assay to monitor the frequency of each allele during long-term maintenance of the resistant colony, cqm1REC was found to predominate early on but later was replaced by cqm1REC-2 as the most abundant resistance allele. Homozygous larvae for each allele were then generated that displayed similar high-resistance phenotypes with equivalent low levels of transcript and lack of protein expression for both cqm1REC and cqm1REC-2. In progeny from a cross of homozygous individuals for each allele at a 1 : 1 ratio, analyzed for ten subsequent generations, cqm1REC showed a higher frequency than cqm1REC-2. The replacement of cqm1REC by cqm1REC -2 observed in the R2362 colony, kept for 210 generations, indicates changes in fitness related to traits that are unknown but linked to these two alleles, and constitutes a unique example of evolution of resistance within a controlled laboratory environment. PMID- 26131742 TI - Advance care planning and end-of-life care in a network of rural Western Australian hospitals. AB - OBJECTIVE: To provide a current perspective on end-of-life (EOL) care in regional Western Australia, with a particular focus on the final admission prior to death and the presence of documented advance care planning (ACP). DESIGN: Retrospective medical notes audit. SETTING: One regional hospital (including colocated hospice) and four small rural hospitals in the Great Southern region of Western Australia. PARTICIPANTS: Ninety recently deceased patients, who died in hospitals in the region. Fifty consecutive patients from the regional hospital and 10 consecutive patients from each of the four rural hospitals were included in the audit. INTERVENTIONS: A retrospective medical notes audit was undertaken. MAIN OUTCOME MEASURES: A 94-item audit tool assessed patient demographics, primary diagnosis, family support, status on admission and presence of documented ACP. Detailed items described the clinical care delivered during the final admission, including communication with family, referral to palliative care, transfers, medical investigations, medical treatments and use of EOL care pathways. RESULTS: Fifty two per cent were women; median age was 82 years old. Forty per cent died of malignancy. Median length of stay was 7 days. Thirty-nine per cent had formal or informal ACP documented. Rural hospitals performed comparably with the regional hospital on all measures. CONCLUSIONS: This study provides benchmarking information that can assist other rural hospitals and suggests ongoing work on optimal methods of measuring quality in EOL care. PMID- 26131743 TI - IL-3 contributes to development of lupus nephritis in MRL/lpr mice. AB - MRL/lpr mice develop a spontaneous autoimmune disease that closely resembles human systemic lupus erythematosus (SLE) with DNA autoantibodies, hypergammaglobulinemia, immune complex glomerulonephritis, and systemic vasculitis. Little is known about the role of IL-3 in SLE. In order to study this we analyzed the expression of IL-3 in murine lupus and determined whether blockade of IL-3 with a monoclonal antibody or injection of recombinant IL-3 affects lupus nephritis in MRL/lpr mice. During disease progression IL-3 levels were increased in the plasma and in the supernatant of cultured splenocytes from MRL/lpr mice. Administration of IL-3 aggravated the disease with significantly higher renal activity scores, more renal fibrosis, and more glomerular leukocyte infiltration and IgG deposition. Blockade of IL-3 significantly improved acute and chronic kidney damage, reduced the glomerular infiltration of leukocytes and the glomerular deposition of IgG, and decreased the development of renal fibrosis. Furthermore, DNA autoantibody production, proteinuria, and serum creatinine levels were significantly lower in the anti-IL-3 group. Thus, IL-3 plays an important role in the pathogenesis of SLE and the progression of lupus nephritis. Hence, blockade of IL-3 may represent a new strategy for treatment of lupus nephritis. PMID- 26131745 TI - [Loeys-Dietz syndrome: aortic dissections and aneurysms]. AB - BACKGROUND: Loeys-Dietz syndrome is a connective tissue disorder accompanied by life-threatening vascular abnormalities such as aneurysms and dissections. Recognising the acute clinical picture is essential for rapid diagnosis and treatment. CASE DESCRIPTION: We describe three members of a family with a typical acute presentation of Loeys-Dietz syndrome, but without the characteristic physical abnormalities. A 40-year-old man presented with a type B aortic dissection and was treated with medication. Shortly afterwards he required emergency surgery for a ruptured aneurysm of the left common iliac artery. He subsequently developed a type A aortic dissection and progressive dilatation of his thoraco-abdominal aorta, for which surgical repair was performed. His sister and brother also presented with type B aortic dissections and both underwent surgery for thoraco-abdominal aortic aneurysms. They died at the age of 50 and 53 respectively. Clinical genetic investigation revealed a mutation of the type 2 receptor of the transforming growth factor beta (TGFbeta) gene. CONCLUSION: Loeys Dietz syndrome is a rare hereditary condition accompanied by acute clinical symptoms. Physical characteristics of the syndrome may be absent. Timely recognition is essential for appropriate treatment and a good prognosis. PMID- 26131744 TI - Mutation in the V2 vasopressin receptor gene, AVPR2, causes nephrogenic syndrome of inappropriate diuresis. AB - Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently discovered rare disease caused by gain-of-function mutations of the V2 vasopressin receptor gene, AVPR2. To date, mutations of Phe229 and Arg137 have been identified as gain-of-function in the V2 vasopressin receptor (V2R). These receptor mutations lead to hyponatremia, which may lead to clinical symptoms in infants. Here we present a newly identified I130N substitution in exon 2 of the V2R gene in a family, causing NSIAD. This I130N mutation resulted in constitutive activity of the V2R with constitutive cyclic adenosine monophosphate (cAMP) generation in HEK293 cells. This basal activity could be blocked by the inverse agonist tolvaptan and arginine-vasopressin stimulation enhanced the cAMP production of I130N-V2R. The mutation causes a biased receptor conformation as the basal cAMP generation activity of I130N does not lead to interaction with beta-arrestin. The constitutive activity of the mutant receptor caused constitutive dynamin-dependent and beta-arrestin-independent internalization. The inhibition of basal internalization using dominant-negative dynamin resulted in an increased cell surface expression. In contrast to the constitutive internalization, agonist-induced endocytosis was beta-arrestin dependent. Thus, tolvaptan could be used for treatment of hyponatremia in patients with NSIAD who carry the I130N-V2R mutation. PMID- 26131746 TI - [Resection of liver metastases in breast cancer]. AB - Liver metastases have the poorest prognosis of all types of breast cancer metastases, with a 5-year survival rate of 0 to 12%. In comparison, the 5-year overall survival rate of patients with colorectal liver metastases undergoing curative liver resection is approximately 30 to 40% and even 50% in selected patients. Partial liver resection in combination with systemic treatment for patients with hepatogenic metastases from breast cancer may lead to improved survival rates for selected patients. PMID- 26131747 TI - [Infantile myofibroma: a neonate with a swelling on the arm]. AB - BACKGROUND: An infantile myofibroma (IM) is a benign congenital soft-tissue tumour. IM is found in 1 per 150,000 live births, making it the most common fibrous tumour of infancy and early childhood. CASE DESCRIPTION: We report on a full-term neonate presenting with an irregular tumour mass on the right lower arm. The mass measured 5 cm in diameter, with surface ulceration. Magnetic resonance imaging (MRI) revealed characteristics that could be consistent with malignancy. On the basis of a biopsy and subsequent polymerase chain reaction we were able to make a diagnosis of 'benign infantile myofibroma'. We chose for conservative treatment in the expectation that the tumour would regress spontaneously. CONCLUSION: Infantile myofibroma should be considered when a newborn presents with an atypical mass. It is difficult to make a diagnosis on the basis of the clinical characteristics alone due to the heterogeneous presentation. A definitive diagnosis can only be made following histological investigation. PMID- 26131748 TI - [Starting and stopping palliative tumour treatment: considerations in the context of quality of life and costs]. AB - Although palliative treatment options are increasing, more emphasis is required on benefits and quality of life, in view of rising costs. Few studies have focused on factors determining decisions regarding treatment choices. The dilemma may involve generally expected patient attitudes such as never giving up on the one hand and limitations in potential and adverse events on the other. WHO performance status, type of cancer and comorbidity influence oncologists' decisions, but many other factors which have not yet been clearly identified may also be involved. Shared decision-making is poorly studied in the palliative setting. Active treatment is most frequently promoted, rather than best supportive care. Patients sometimes feel insufficiently informed. Quality adjusted life years assessment may add to decision-making. Involving palliative care expertise, and collaborating with oncologists and general physicians, may be of value regarding decision-making. Introduction of more objective parameters to outweigh benefits and burden of (maintaining) palliative tumour-directed treatment is required. PMID- 26131749 TI - [A woman with a symptomatic abdominal swelling]. AB - A 51-year-old woman visited the surgery outpatient clinic with an abdominal swelling. The swelling had become larger over the past few years and caused mechanical complaints. With MRI a liver cyst measuring 14 x 11 cm was diagnosed. The patient underwent laparoscopic deroofing of the liver cyst. PMID- 26131750 TI - [A woman with painful ulcera on her lower leg]. AB - A 49-year-old woman presented with painful ulcera on her right lower leg. She was known with Crohn's disease. Wound cultures were negative. Based on clinical findings she was diagnosed with pyoderma gangrenosum. After treatment with topical glucocorticoids and intravenous infliximab and ciclosporin, the ulcera gradually disappeared. PMID- 26131751 TI - [An infant with a bowed lower leg]. AB - The parents of a 5-month-old boy noticed bowing of his left leg. Radiographic survey showed an anterolateral bowing of the left tibia and fibula with intramedullary sclerosis, typical for neurofibromatosis type 1. As the mother had neurofibromatosis, this boy was diagnosed with neurofibromatosis type 1. PMID- 26131752 TI - [Healthcare in snapshots]. AB - Healthcare is becoming more complex and healthcare providers are often only involved in a small part of the process of patient care. Measuring the outcome of the process, in this case healthcare-related infections, with feedback to the professionals involved is indispensable for assessment and improvement of quality of care. Prevalence surveys are used frequently to determine the quality of the process. This method has important limitations that can lead to a biased result. This problem is discussed on the basis of a case and a recent publication on healthcare-related infections occurring after discharge. PMID- 26131753 TI - [Central arteriovenous anastomosis: the solution for patients with treatment resistant hypertension?]. AB - New non-pharmacological therapies for the treatment of resistant hypertension, such as baroreflex stimulation, renal denervation and barostenting, have recently been introduced. The latest development is lowering blood pressure by creating an arteriovenous anastomosis between the common iliac vein and artery by means of a metal coupler device. The randomised, non-blinded ROX CONTROL HTN study showed that office systolic blood pressure was reduced by 27 mmHg in patients assigned to arteriovenous coupler therapy, compared with a reduction of 4 mmHg in patients assigned to normal care. As this was not a double-blind, sham-controlled study, caution is needed. Complications related to the procedure or device were seen in 60% of patients in the intervention group. The most common complication was venous stenosis. Questions remain regarding the exact working mechanism, size and duration of the effects on blood pressure. There are also concerns about adverse effects. PMID- 26131754 TI - Characterization of Thymic Settling Progenitors in the Mouse Embryo Using In Vivo and In Vitro Assays. AB - Characterizing thymic settling progenitors is important to understand the pre thymic stages of T cell development, essential to devise strategies for T cell replacement in lymphopenic patients. We studied thymic settling progenitors from murine embryonic day 13 and 18 thymi by two complementary in vitro and in vivo techniques, both based on the "hanging drop" method. This method allowed colonizing irradiated fetal thymic lobes with E13 and/or E18 thymic progenitors distinguished by CD45 allotypic markers and thus following their progeny. Colonization with mixed populations allows analyzing cell autonomous differences in biologic properties of the progenitors while colonization with either population removes possible competitive selective pressures. The colonized thymic lobes can also be grafted in immunodeficient male recipient mice allowing the analysis of the mature T cell progeny in vivo, such as population dynamics of the peripheral immune system and colonization of different tissues and organs. Fetal thymic organ cultures revealed that E13 progenitors developed rapidly into all mature CD3(+) cells and gave rise to the canonical gammadelta T cell subset, known as dendritic epithelial T cells. In comparison, E18 progenitors have a delayed differentiation and were unable to generate dendritic epithelial T cells. The monitoring of peripheral blood of thymus-grafted CD3(-/-) mice further showed that E18 thymic settling progenitors generate, with time, larger numbers of mature T cells than their E13 counterparts, a feature that could not be appreciated in the short term fetal thymic organ cultures. PMID- 26131755 TI - Brain Source Imaging in Preclinical Rat Models of Focal Epilepsy using High Resolution EEG Recordings. AB - Electroencephalogram (EEG) has been traditionally used to determine which brain regions are the most likely candidates for resection in patients with focal epilepsy. This methodology relies on the assumption that seizures originate from the same regions of the brain from which interictal epileptiform discharges (IEDs) emerge. Preclinical models are very useful to find correlates between IED locations and the actual regions underlying seizure initiation in focal epilepsy. Rats have been commonly used in preclinical studies of epilepsy; hence, there exist a large variety of models for focal epilepsy in this particular species. However, it is challenging to record multichannel EEG and to perform brain source imaging in such a small animal. To overcome this issue, we combine a patented technology to obtain 32-channel EEG recordings from rodents and an MRI probabilistic atlas for brain anatomical structures in Wistar rats to perform brain source imaging. In this video, we introduce the procedures to acquire multichannel EEG from Wistar rats with focal cortical dysplasia, and describe the steps both to define the volume conductor model from the MRI atlas and to uniquely determine the IEDs. Finally, we validate the whole methodology by obtaining brain source images of IEDs and compare them with those obtained at different time frames during the seizure onset. PMID- 26131756 TI - Fatty Acid Chain Length Dependence of Phase Separation Kinetics in Stratum Corneum Models by IR Spectroscopy. AB - The main barrier to permeability in human skin resides in the stratum corneum (SC), a layered structure consisting of anucleated, flattened cells (corneocytes) embedded in a heterogeneous lamellar lipid matrix. While lipid structures and packing propensities in the SC and in SC models have been extensively investigated, only limited data are available concerning the kinetics and mechanism of formation of lamellar phases and particular lipid packing motifs. In our prior investigation, kinetic IR spectroscopy measurements probed the temporal sequence of phase separation leading to ordered structures in a three component SC model of equimolar structurally heterogeneous ceramide[NS], chain perdeuterated stearic acid, and cholesterol. In the current work, the phase separation kinetic effects of specific fatty acid chain lengths with a synthetic structurally homogeneous ceramide[NS] in similar ternary mixtures are examined. These are compared with a mixture containing ceramide[NS] with an unsaturated acid chain. The kinetic events are sensitive to the difference in chain lengths between the ceramide acid chain and the fatty acid as well as to the presence of unsaturation in the former. The observed kinetic behaviors span a wide range of phase separation times, ranging from the formation of a solid solution stable for at least 200 h, to a system in which an orthorhombic fatty acid structure is essentially completely formed within the time resolution of the experiment (15 min). The data seem to offer some features of a spinodal phase separation at relatively short times. Overall the approach offers a possible means for addressing several unanswered questions pertinent to skin pharmacology, such as the roles of a wide variety of ceramide and fatty acid species and the design of therapeutic interventions for repair of pathological conditions of the SC. PMID- 26131757 TI - Biology of childhood acute lymphoblastic leukemia (ALL) in low/middle-income countries--A case for using age at diagnosis for defining low-risk all. PMID- 26131758 TI - POPs and Gut Microbiota: Dietary Exposure Alters Ratio of Bacterial Species. PMID- 26131759 TI - Trajectories of Depressive Symptoms in Elderly Mexican Americans. AB - OBJECTIVES: To identify depressive symptom trajectories and factors associated with trajectory group membership in the very old segment of the rapidly growing and long-living Mexican-American population. DESIGN: Latent growth curve modeling was used to identify depressive symptom trajectories and multinomial logistic regression to identify factors associated with trajectory group membership. SETTING: Data spanning three waves and 7 years (2004-05, 2007-08, 2010-11) drawn from the Hispanic Established Populations for Epidemiologic Studies of the Elderly; homes of Mexican-origin elderly adults. PARTICIPANTS: Community-dwelling Mexican Americans aged 75 and older living in the southwestern United States (N = 1,487). MEASUREMENTS: The 20-item version of the Center for Epidemiologic Studies Depression Scale. RESULTS: Three trajectory groups were identified: low throughout, increasing, and high but decreasing. Activity of daily living disability was the strongest predictor of depressive symptoms, followed by social support. Foreign-born individuals were at greater risk than those who are U.S. born for high but decreasing depressive symptoms than for low depressive symptoms. CONCLUSION: Early detection and treatment of chronic disabling conditions, especially heart disease, cancer, visual impairment, and cognitive impairment, and increasing access to social participation should be the focus of treatment and intervention strategies for depression in very old Mexican Americans. PMID- 26131760 TI - Understanding Perceived Benefit of Early Cancer Detection: Community-Partnered Research with African American Women in South Los Angeles. AB - BACKGROUND: African American women have lower 5-year cancer survival rates than non-Latino White women. Differences in perceived benefits of early cancer detection among racial/ethnic groups may affect cancer-screening behaviors. This study assessed correlates of perceived benefits of early breast, cervical and colorectal cancer detection among 513 African American women. METHODS: Using a community-partnered participatory research approach, we conducted a survey on cancer screening, risk behaviors, and related knowledge and attitudes among African American parishioners at 11 churches in South Los Angeles, a neighborhood that experiences one of the highest cancer mortality rates in California. RESULTS: African American women who participated in this study were more likely to believe that chances for survival are very good or good after early detection of breast cancer (74%) than after early detection of colorectal (51%) and cervical cancer (52%). Multivariate analyses show that perceived benefit of early cancer detection is associated with higher cancer knowledge and having discussed one's cancer risk with a doctor. CONCLUSIONS: Given that 5-year survival rates for early stage breast, cervical, and colorectal cancer range from 84% to 93%, our data suggest that a substantial proportion of African American women in South Los Angeles are not aware of the benefits of early detection, particularly of colorectal and cervical cancers. Programs that increase cancer knowledge and encourage a discussion of individual's cancer risk with a doctor may be able to increase perceived benefit of early detection, a construct that has been shown to be associated with cancer screening in some studies. PMID- 26131761 TI - Higher-Order Cyclopropenimine Superbases: Direct Neutral Bronsted Base Catalyzed Michael Reactions with alpha-Aryl Esters. AB - The synthesis and characterization of six new classes of higher-order superbases, including five that incorporate cyclopropenimine functionality, has been achieved. We propose a nomenclature that designates these as the CG2, GC2, PC3, PC1, C3, and GP2 classes of superbases. The pK(BH+) values were measured to be between 29.0 and 35.6 in acetonitrile. Linear correlations of ten superbase basicities vs that of their substituents demonstrated the insulating effect of the cyclopropenimine core. The molecular structures of several of these materials were obtained by single-crystal X-ray analysis, revealing interesting aspects of conformational bias and noncovalent organization. The types of superbasic cores and substituents were each reliably shown to affect selectivity for deprotonation over alkylation. Higher-order cyclopropenimine and guanidine superbase stability to hydrolysis was found to correlate to basicity. Finally, a GC2 base was found to catalyze conjugate additions of alpha-aryl ester pronucleophiles, representing the first report of a neutral Bronsted base to catalyze such reactions. PMID- 26131762 TI - Use of a Field Portable X-Ray Fluorescence Analyzer for Environmental Exposure Assessment of a Neighborhood in Cairo, Egypt Adjacent to the Site of a Former Secondary Lead Smelter. AB - The objectives of this study are to demonstrate for the first time the use of a field portable X-Ray Fluorescence Analyzer (XRF) in a multi-media environmental survey and to use the survey results to determine if residual lead from a once active secondary lead smelter in Cairo, Egypt, still posed a health risk to the residents when comparing results with US EPA standards. Results were analyzed to determine if relationships among the variables indicated that there were residual impacts of the former smelter. Samples collected inside and near a total of 194 dwellings were analyzed. The mean floor dust lead loading was 7.48 MUg lead/ft(2). Almost 10% of the dwellings had at least one floor dust wipe sample that exceeded the United States Environmental Protection Agency's (USEPA) interior settled dust lead level of 40 MUg lead/ft(2). The median paint lead level was 0.04 mg lead/cm(2). 17% of the dwellings had at least one interior paint sample that exceeded the USEPA standard of 1.0 mg lead/cm(2). Mean soil lead concentration in the study area was 458 ppm and 91 ppm outside the study area. Four of nine composite soil samples exceeded the US EPA limit for bare soil in play areas. Lead concentrations in samples collected in locations outside the study area did not exceed the limit. The highest concentration was in the plot closest to the smelter and may represent residual impact from the former smelter. Statistically significant relationships were not detected between interior floor dust lead loading and either interior paint lead loading or exterior dust lead concentration. Thus, no significant exposure from the former smelter was indicated by these analyses. This may have resulted from the time elapsed since the closing of the smelter and/or the relatively low paint lead levels. Further study is needed in other areas of Egypt near former and active lead smelters. Elevated levels of mercury and arsenic detected in soil samples do not appear to be related to the smelter but warrant further study. PMID- 26131763 TI - Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials. AB - Numerous studies have investigated the effects of folic acid supplementation on colorectal cancer risk, but conflicting results were reported. We herein performed a meta-analysis based on relevant studies to reach a more definitive conclusion. The PubMed and Embase databases were searched for quality randomized controlled trials (RCTs) published before October 2014. Eight articles met the inclusion criteria and were subsequently analyzed. The results suggested that folic acid treatment was not associated with colorectal cancer risk in the total population (relative risk [RR] = 1.00, 95% confidence interval [CI] = 0.82-1.22, P = 0.974). Moreover, no statistical effect was identified in further subgroup analyses stratified by ethnicity, gender, body mass index (BMI) and potential confounding factors. No significant heterogeneity or publication bias was observed. In conclusion, our meta-analysis demonstrated that folic acid supplementation had no effect on colorectal cancer risk. However, this finding must be validated by further large studies. PMID- 26131765 TI - Effects of Integrating and Non-Integrating Reprogramming Methods on Copy Number Variation and Genomic Stability of Human Induced Pluripotent Stem Cells. AB - Human-induced pluripotent stem cells (iPSCs) are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors ("integrating iPSC lines"), 6 iPSC lines derived using non integrating vectors ("non-integrating iPSC lines"), and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV), loss of heterozygosity (LOH) and mosaicism patterns of integrating and non integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA (International Symposium on Computer Architecture) database were highest in integrating iPSC lines. Different single nucleotide polymorphisms (SNP) calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high resolution method to monitor genomic aberrations in iPSCs intended for clinical applications to avoid any negative effects of reprogramming or cell culture. PMID- 26131764 TI - Estimating first-passage time distributions from weighted ensemble simulations and non-Markovian analyses. AB - First-passage times (FPTs) are widely used to characterize stochastic processes such as chemical reactions, protein folding, diffusion processes or triggering a stock option. In previous work (Suarez et al., JCTC 2014;10:2658-2667), we demonstrated a non-Markovian analysis approach that, with a sufficient subset of history information, yields unbiased mean first-passage times from weighted ensemble (WE) simulations. The estimation of the distribution of the first passage times is, however, a more ambitious goal since it cannot be obtained by direct observation in WE trajectories. Likewise, a large number of events would be required to make a good estimation of the distribution from a regular "brute force" simulation. Here, we show how the previously developed non-Markovian analysis can generate approximate, but highly accurate, FPT distributions from WE data. The analysis can also be applied to any other unbiased trajectories, such as from standard molecular dynamics simulations. The present study employs a range of systems with independent verification of the distributions to demonstrate the success and limitations of the approach. By comparison to a standard Markov analysis, the non-Markovian approach is less sensitive to the user-defined discretization of configuration space. PMID- 26131766 TI - Self-Assembled Hybrid Aptamer-Fc Conjugates for Targeted Delivery: A Modular Chemoenzymatic Approach. AB - Over the past decade, DNA and RNA aptamers have attracted keen research interest due to their ability to specifically bind targets of therapeutic relevance. However, their application is often hampered by a short serum half-life and missing effector functions. Conjugation of aptamers to antibody Fc fragments could improve pharmacokinetics, enable immune effector mechanisms, and provide an option for the introduction of desired payloads (e.g., toxins or fluorescent dyes). We developed a modular scaffold-supported system based on human IgG1 Fc fragments, which allows for its dual functionalization with moieties of interest. In our approach, two bioorthogonal, enzyme-mediated reactions were used in combination with oxime ligation and self-assembly based on PNA-DNA base pairing. Thus, an engineered synthetic peptide nucleic acid (PNA) oligomer was coupled to the C-termini of the Fc dimer upon sequence-specific sortase A-mediated transpeptidation. Hybridization of the resulting Fc-PNA conjugate with a tailored DNA aptamer that binds cancer-related hepatocyte growth factor receptor (c-MET) led to a hybrid construct which showed strong and specific binding to c-MET and was readily internalized by c-MET-overexpressing cells. To install an additional orthogonally addressable site, aldehyde tag technology was applied followed by oxime ligation with an aminooxy-bearing fluorescent dye as model cargo. Delivery of fluorescent probe specifically to c-MET-overexpressing cells was confirmed by flow cytometry. Our approach can provide access to engineered aptamer-Fc conjugates with desired target specificity and cytotoxic payloads. PMID- 26131767 TI - A New Eocene Casquehead Lizard (Reptilia, Corytophanidae) from North America. AB - A new fossil showing affinities with extant Laemanctus offers the first clear evidence for a casquehead lizard (Corytophanidae) from the Eocene of North America. Along with Geiseltaliellus from roughly coeval rocks in central Europe, the new find further documents the tropical fauna present during greenhouse conditions in the northern mid-latitudes approximately 50 million years ago (Ma). Modern Corytophanidae is a neotropical clade of iguanian lizards ranging from southern Mexico to northern South America. PMID- 26131768 TI - Recent Changes in the Prevalence of and Factors Associated With Frequency of Indoor Tanning Among US Adults. PMID- 26131769 TI - Venom Proteins from Parasitoid Wasps and Their Biological Functions. AB - Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies. PMID- 26131770 TI - Therapeutic Effects of Bee Venom on Immunological and Neurological Diseases. AB - Bee Venom (BV) has long been used in Korea to relieve pain symptoms and to treat inflammatory diseases, such as rheumatoid arthritis. The underlying mechanisms of the anti-inflammatory and analgesic actions of BV have been proved to some extent. Additionally, recent clinical and experimental studies have demonstrated that BV and BV-derived active components are applicable to a wide range of immunological and neurodegenerative diseases, including autoimmune diseases and Parkinson's disease. These effects of BV are known to be mediated by modulating immune cells in the periphery, and glial cells and neurons in the central nervous system. This review will introduce the scientific evidence of the therapeutic effects of BV and its components on several immunological and neurological diseases, and describe their detailed mechanisms involved in regulating various immune responses and pathological changes in glia and neurons. PMID- 26131771 TI - Analgesic Effects of Bee Venom Derived Phospholipase A(2) in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain. AB - A single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms. Our recent study demonstrated that BV alleviates oxaliplatin-induced cold allodynia in rats, via noradrenergic and serotonergic analgesic pathways. In this study, we have further investigated whether BV derived phospholipase A2 (bvPLA2) attenuates oxaliplatin-induced cold and mechanical allodynia in mice and its mechanism. The behavioral signs of cold and mechanical allodynia were evaluated by acetone and a von Frey hair test on the hind paw, respectively. The significant allodynia signs were observed from one day after an oxaliplatin injection (6 mg/kg, i.p.). Daily administration of bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days markedly attenuated cold and mechanical allodynia, which was more potent than the effect of BV (1 mg/kg, i.p.). The depletion of noradrenaline by an injection of N-(2 chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 50 mg/kg, i.p.) blocked the analgesic effect of bvPLA2, whereas the depletion of serotonin by injecting DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for three successive days did not. Furthermore, idazoxan (alpha2-adrenegic receptor antagonist, 1 mg/kg, i.p.) completely blocked bvPLA2-induced anti-allodynic action, whereas prazosin (alpha1-adrenegic antagonist, 10 mg/kg, i.p.) did not. These results suggest that bvPLA2 treatment strongly alleviates oxaliplatin-induced acute cold and mechanical allodynia in mice through the activation of the noradrenergic system, via alpha2-adrenegic receptors, but not via the serotonergic system. PMID- 26131772 TI - An Insight into the Sialome of the Lone Star Tick, Amblyomma americanum, with a Glimpse on Its Time Dependent Gene Expression. AB - Hard ticks feed for several days or weeks on their hosts. Blood feeding is assisted by tick saliva, which is injected in the host skin regularly, alternating with blood ingestion. Tick saliva contains hundreds or thousands of different peptides and other bioactive compounds that assist feeding by inhibiting their hosts' blood clotting, platelet aggregation, vasoconstriction, as well as pain and itching. Immunomodulatory and antimicrobial peptides are also found in tick saliva. Molecular characterization of tick salivary compounds, or its sialome (from the Greek sialos = saliva), helps identification of possible antigens that might confer anti-tick immunity, as well as identifying novel pharmacologically active compounds. Amblyomma americanum is a major nuisance tick in Eastern and Southern US, being a vector of Theileria and Ehrlichia bacteria to animals and humans. Presently we report an RNAseq study concerning the salivary glands of adult female A. americanum ticks, which involved sequencing of four libraries collected at different times of feeding. A total of 5,792 coding sequences were deduced from the transcriptome assembly, 3,139 of which were publicly deposited, expanding from the previously available 146 salivary sequences found in GenBank. A remarkable time-dependent transcript expression was found, mostly related to secretory products, supporting the idea that ticks may have several "sialomes" that are expressed at different times during feeding. The molecular nature of this sialome switching remains unknown. The hyperlinked spreadsheet containing the deduced coding sequences can be found at http://exon.niaid.nih.gov/transcriptome/Amb_americanum/Ambame-web.xlsx. PMID- 26131773 TI - Bimetallic cobalt-dinitrogen complexes: impact of the supporting metal on N2 activation. AB - Expanding a family of cobalt bimetallic complexes, we report the synthesis of the Ti(III) metalloligand, Ti[N(o-(NCH2P((i)Pr)2)C6H4)3] (abbreviated as TiL), and three heterobimetallics that pair cobalt with an early transition metal ion: CoTiL (1), K(crypt-222)[(N2)CoVL] (2), and K(crypt-222)[(N2)CoCrL] (3). The latter two complexes, along with previously reported K(crypt-222)[(N2)CoAlL] and K(crypt-222)[(N2)Co2L], constitute an isostructural series of cobalt bimetallics that bind dinitrogen in an end-on fashion, i.e. [(N2)CoML](-). The characterization of 1-3 includes cyclic voltammetry, X-ray crystallography, and infrared spectroscopy. The [CoTiL](0/-) reduction potential is extremely negative at -3.20 V versus Fc(+)/Fc. In the CoML series where M is a transition metal, the reduction potentials shift anodically as M is varied across the first-row period. Among the [(N2)CoML](-) compounds, the dinitrogen ligand is weakly activated, as evidenced by N-N bond lengths between 1.110(8) and 1.135(4) A and by N-N stretching frequencies between 1971 and 1995 cm(-1). Though changes in nuN2 are subtle, the extent of N2 activation decreases across the first-row period. A correlation is found between the [CoML](0/-) reduction potentials and N2 activation, where the more cathodic potentials correspond to lower N-N frequencies. Theoretical calculations of the [(N2)CoML](-) complexes reveal important variations in the electronic structure and Co-M interactions, which depend on the exact nature of the supporting metal ion, M. PMID- 26131774 TI - Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy. AB - Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real time +/-4 cm pan-and-tilt action. Robot-driven +/-60 degrees pivots of an integrated +/-185 degrees rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2 [(18)F] fluoro-2-deoxy-?-glucose ((18)F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less. In this article, we describe new radiation plans for the treatment of moving lung tumors. PMID- 26131781 TI - Retropubic Intracorporeal Placement of a Suburethral Autologous Sling During Robot-Assisted Radical Prostatectomy to Improve Early Urinary Continence Recovery: Preliminary Data. AB - BACKGROUND AND PURPOSE: Urinary continence (UC) recovery remains bothersome for patients even after robot-assisted radical prostatectomy (RARP). We describe the first retropubic suburethral autologous sling created and placed during RARP. The surgical technique and preliminary data regarding its effectiveness in improving early UC recovery are presented. PATIENTS AND METHODS: Between November 2013 and February 2014, 60 patients who underwent RARP at a single high-volume center were prospectively randomized into sling and nonsling groups. Early UC was assessed at 5 days (time of catheter removal), 10 days, and 30 days postoperatively by the daily number of pads used and the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) score. Sling-related operative time and urethral erosion were also analyzed. Chi-square and independent sample t tests were used to investigate surgical and functional outcomes between groups. RESULTS: Complete data were available for all patients. Mean +/- standard deviation (SD) numbers of pads used daily in nonsling and sling groups, respectively, were 1.9 +/- 1.2 versus 1.7 +/- 1.4 (P = 0.5) at 5 days, 1.8 +/- 1.3 versus 1.3 +/- 1.3 (P = 0.1) at 10 days, and 1.1 +/- 1.2 versus 0.4 +/- 0.8 (P = 0.01) at 30 days. At 1 month, mean +/- SD ICIQ-UI-SF scores in nonsling and sling groups, respectively, were 4.8 +/- 4.6 versus 1.8 +/- 3.4 (P = 0.01); sling patients were associated with pad-free status (76% vs 46%, P = 0.03). The advantage in UC recovery was also observed in sling patients at 3, 6, and 12 months postoperatively. Surgical time did not differ between groups, and in sling patients, no cases of urethral erosion or uroflowmetry suggestive of urinary obstruction were found. Limitations included the small sample size and the lack of assessment of morphologic and urodynamic changes produced by the sling. CONCLUSIONS: The suburethral autologous sling is technically feasible and may improve early UC recovery after RARP. These preliminary results should be confirmed in a larger sample of patients. PMID- 26131782 TI - Is heart-rate complexity a surrogate measure of cardiac output before, during, and after hemorrhage in a conscious sheep model of multiple hemorrhages and resuscitation? AB - BACKGROUND: Despite its medical utility, continuous cardiac output (CO) monitoring remains a practical challenge on the battlefield and in the prehospital environment. Measuring a CO surrogate, perhaps heart-rate complexity (HRC), might be a viable solution when no direct monitoring of CO is available. Changes in HRC observed before and during hemorrhagic shock may be able to track the simultaneous changes in CO. The goal of this study was to test whether HRC is a surrogate measure of CO before, during, and after hemorrhage in a conscious sheep model of multiple hemorrhages and resuscitation. METHODS: HRC was derived from 100-Hz electrocardiograms of 10 sheep records, 3 hours to 4 hours long, using the method of sample entropy. A real-time detection algorithm was used to detect the R-R interval sequences for HRC calculations. All records contained 100 Hz recordings of pulmonary arterial blood flow using Doppler transit time (criterion standard CO). Gold CO and estimated HRC values were analyzed using overlaid time-synchronized waveform plots as well as Bland-Altman, regression, and four-quadrant analysis. RESULTS: Baseline CO varied from 3.0 L/min to 5.4 L/min, while posthemorrhage CO varied from 1.0 L/min to 1.8 L/min. Importantly, overlaid plots demonstrated an overall high similarity between CO and HRC waveforms before and during hemorrhage, but not during resuscitation. When the electrocardiogram quality was high, the correlation between CO and HRC within the first 45 minutes was greater than 0.75 (p < 0.0001; maximum r, 0.972). Scatter plots also depicted high linearity before and during hemorrhage. Four-quadrant analysis showed that instantaneous changes between consecutive beat-to-beat HRC measurements followed CO measurements (100% concordance rate), while 5-minute time points yielded a 76.19% concordance rate. CONCLUSION: HRC has potential utility as a noninvasive tool for assessing the response of CO to life threatening injuries such as hemorrhagic shock. However, further investigation and other animal models or human studies are needed. PMID- 26131783 TI - A comparison of live tissue training and high-fidelity patient simulator: A pilot study in battlefield trauma training. AB - BACKGROUND: Trauma procedural and management skills are often learned on live tissue. However, there is increasing pressure to use simulators because their fidelity improves and as ethical concerns increase. We randomized military medical technicians (medics) to training on either simulators or live tissue to learn combat casualty care skills to determine if the choice of modality was associated with differences in skill uptake. METHODS: Twenty medics were randomized to trauma training using either simulators or live tissue. Medics were trained to perform five combat casualty care tasks (surgical airway, needle decompression, tourniquet application, wound packing, and intraosseous line insertion). We measured skill uptake using a structured assessment tool. The medics also completed exit questionnaires and interviews to determine which modality they preferred. RESULTS: We found no difference between groups trained with live tissue versus simulators in how they completed each combat casualty care skill. However, we did find that the modality of assessment affected the assessment score. Finally, we found that medics preferred trauma training on live tissue because of the fidelity of tissue handling in live tissue models. However, they also felt that training on simulators also provided additional training value. CONCLUSION: We found no difference in performance between medics trained on simulators versus live tissue models. Even so, medics preferred live tissue training over simulation. However, more studies are required, and future studies need to address the measurement bias of measuring outcomes in the same model on which the study participants are trained. LEVEL OF EVIDENCE: Therapeutic/care management study, level II. PMID- 26131784 TI - Chronic safety assessment of hemostatic self-expanding foam: 90-day survival study and intramuscular biocompatibility. AB - BACKGROUND: Noncompressible hemorrhage is a significant cause of preventable death in trauma, with no effective presurgical treatments. We previously described the efficacy and 28-day safety of a self-expanding hemostatic foam in swine models. We hypothesized that the 28-day results would be confirmed at a second site and that results would be consistent over 90 days. Finally, we hypothesized that the foam material would be biocompatible following intramuscular implantation. METHODS: Foam treatment was administered in swine following a closed-cavity splenic injury. The material was explanted after 3 hours, and the animals were monitored to 28 days (n = 6) or 90 days (n = 4). Results were compared with a control group with injury alone (n = 6 at 28 days, n = 3 at 90 days). In a separate study, foam samples were implanted in rabbit paravertebral muscle and assessed at 28 days and 90 days relative to a Food and Drug Administration-approved polyurethane mesh (n = 3 per group). RESULTS: All animals survived the acute phase of the study, and the foam animals required enterorrhaphy. One animal developed postoperative ileus and was euthanized; all other animals survived to the 28-day or 90-day end point without clinically significant complications. Histologic evaluation demonstrated that remnant particles were associated with a fibrotic capsule and mild inflammation. The foam was considered biocompatible in 28-day and 90-day intramuscular implant studies. CONCLUSION: Foam treatment was not associated with significant evidence of end organ dysfunction or toxicity at 28 days or 90 days. Remnant foam particles were well tolerated. These results support the long-term safety of this intervention for severely bleeding patients. PMID- 26131785 TI - Causes of combat ocular trauma-related blindness from Operation Iraqi Freedom and Enduring Freedom. AB - BACKGROUND: The incidence of eye injuries in military service members is high in the combat setting. This is the first study that identifies the primary reason for poor visual acuity (worse than 20/200). METHODS: This is a retrospective, noncomparative, interventional case series analyzing US Operation Iraqi and Enduring Freedom members who were evacuated from the theater of operations to Walter Reed Army Medical Center from 2001 through 2011. Primary outcome measures were the length of follow-up, globe survival, and anatomic causes of blindness. Secondary outcome measures included surgical procedures performed, use of eye protection, nonocular injuries, incidence of traumatic brain injury, source of injury, visual outcomes, and predictability of Ocular Trauma Score (OTS) on visual outcome. Univariate analysis was performed using chi and Fisher's exact test. A p < 0.01 was considered significant because of the multiple hypotheses tested. RESULTS: There were 265 eyes of 239 patients who had final best-corrected visual acuity of worse than 20/200. The average age was 27.4 years (range, 19-53 years). Of the patients, 97.5% were male, and 28.9% had documented use of eye protection. The average follow-up was 350.19 days (range, 3-2,421 days). There were 128 right-eye and 133 left-eye injuries, with a total of 26 bilateral injuries. There were 206 open-globe and 56 closed-globe injuries, which were further subdivided into zones. Open-globe Zone III injuries (81.6%) were the number one cause of blindness, and most injuries were caused by improvised explosive devices (64.2%). Enucleation was the most common surgery performed (40.6%) and therefore the leading cause of blindness, followed by a multifactorial cause and direct traumatic optic neuropathy. CONCLUSION: Ocular trauma is common among combat injuries. Close to a third of service members that experience an ocular trauma become legally blind. Further research is needed to focus on strategies to prevent injury and improve visual outcomes. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level V. PMID- 26131786 TI - Rhabdomyolysis and acute kidney injury in the injured war fighter. AB - BACKGROUND: Rhabdomyolysis is a recognized complication of traumatic injury. The correlation of an elevated creatine kinase (CK) level and the development of acute kidney injury (AKI) has been studied in the civilian population. We sought to review the prevalence of rhabdomyolysis in injured war fighters and determine if peak CK levels correlate with AKI. METHODS: This is a retrospective cohort study of patients admitted at a US military treatment facility from January to November 2010. Inclusion criteria were active duty patients transported after explosive, penetrating, or blunt injury. Patients with burns or non-trauma related admissions were excluded. Rhabdomyolysis was defined as a CK level greater than 5,000 U/L. AKI was defined using the Kidney Disease: Improving Global Outcomes classification. Mann-Whitney U-tests were used to determine the significance for continuous data. Correlations were determined using Spearman's rho. Significance was set at p < 0.05. RESULTS: Of the 318 patients included in our analysis, 310 (98%) were male, and the median age was 24 years (21-28 years). Blast was the predominant mechanism of injury (71%), with a median Injury Severity Score (ISS) of 22 (16-29). Rhabdomyolysis developed in 79 patients (24.8%). The median peak CK for all patients was 4,178 U/L and ranged from 208 U/L to 120,000 U/L. Stage 1, 2, and 3 AKI developed in 56 (17.6%), 3 (0.9%), and 7 (2.2%) patients, respectively. There was a weak but statistically significant correlation between peak CK and AKI (r = 0.26, p < 0.05). CONCLUSION: Elevated peak CK levels in the injured war fighter are weakly associated with the development of AKI but are not predictive. The development of clinical practice guidelines would help standardize treatment for rhabdomyolysis in combat casualties and would allow for standardized comparisons in future work. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III. PMID- 26131787 TI - The impact of blood transfusions in deceased organ donors on the outcomes of 1,884 renal grafts from United Network for Organ Sharing Region 5. AB - BACKGROUND: Historically, strategies to reduce acute rejection and improve graft survival in kidney transplant recipients included blood transfusions (BTs) before transplantation. While advents in recipient immunosuppression strategies have replaced this practice, the impact of BTs in the organ donor on recipient graft outcomes has not been evaluated. We hypothesize that BTs in organ donors after neurologic determination of death (DNDDs) translate into improved recipient renal graft outcomes, as measured by a decrease in delayed graft function (DGF). METHODS: Donor demographics, critical care end points, the use of BTs, and graft outcome data were prospectively collected on DNDDs from March 2012 to October 2013 in the United Network for Organ Sharing Region 5 Donor Management Database. Propensity analysis determined each DNDD's probability of receiving packed red blood cells based on demographic and critical care data as well as provider bias. The primary outcome measure was the rate of DGF (dialysis in the first week after transplantation) in different donor BT groups as follows: no BT, any BT, 1 to 5, 6 to 10, or greater than 10 packed red blood cell units. Regression models determined the relationship between donor BTs and recipient DGF after accounting for known predictors of DGF as well as the propensity to receive a BT. RESULTS: Data were complete for 1,884 renal grafts from 1,006 DNDDs; 52% received any BT, 32% received 1 to 5 U, 11% received 6 to 10, and 9% received greater than 10 U of blood. Grafts from transfused donors had a lower rate of DGF compared with those of the nontransfused donors (26% vs. 34%, p < 0.001). After adjusting for known confounders, grafts from donors with any BT had a lower odds of DGF (odds ratio, 0.76; p = 0.030), and this effect was greatest in those with greater than 10 U transfused. CONCLUSION: Any BT in a DNDD was associated with a 23% decrease in the odds of recipients developing DGF, and this effect was more pronounced as the number of BTs increased. LEVEL OF EVIDENCE: Therapeutic study, level III; epidemiologic/prognostic study, level II. PMID- 26131788 TI - Just-in-time learning is effective in helping first responders manage weapons of mass destruction events. AB - BACKGROUND: Chemical, biologic, radiologic, nuclear, and explosive (CBRNE) incidents require specialized training. The low frequency of these events leads to significant skill decay among first responders. To address skill decay and lack of experience with these high-impact events, educational modules were developed for mobile devices to provide just-in-time training to first responders en route to a CBRNE event. This study assessed the efficacy and usability of the mobile training. METHODS: Ninety first responders were randomized to a control or an intervention group. All participants completed a pretest to measure knowledge of CBRNE topics. The intervention group then viewed personal protective equipment and weapons of mass destruction field management videos as an overview. Both groups were briefed on a disaster scenario (chemical nerve agent, radiologic, or explosives) requiring them to triage, assess, and manage a patient. Intervention group participants watched a mobile training video corresponding to the scenario. The control group did not receive prescenario video training. Observers rated participant performance in each scenario. After completing the scenarios, all participants answered a cognitive posttest. Those in the intervention group also answered a questionnaire on their impressions of the training. RESULTS: The intervention group outperformed the control group in the explosives and chemical nerve agent scenarios; the differences were statistically significant (explosives, mean of 26.32 for intervention and 22.85 for control, p < 0.01; nerve agent, mean of 23.14 for intervention and 16.61 for control, p < 0.01). There was no statistically significant difference between the groups in the radiologic scenario (mean, 12.7 for intervention and 11.8 for control; p = 0.51). The change in pretest to posttest cognitive scores was significantly higher in the intervention group than in the control group (t = 3.28, p < 0.05). CONCLUSION: Mobile just-in-time training improved first-responder knowledge of CBRNE events and is an effective tool in helping first responders manage simulated explosive and chemical agent scenarios. LEVEL OF EVIDENCE: Therapeutic/care management study, level II. PMID- 26131789 TI - The effects of combat-related mild traumatic brain injury (mTBI): Does blast mTBI history matter? AB - BACKGROUND: The effects of mild traumatic brain injury (mTBI) have received significant attention since the beginning of the conflicts in Afghanistan and Iraq. Surprisingly, little is known about the temporal nature of neurocognitive impairment, mTBI, and posttraumatic stress (PTS) symptoms following combat related mTBI. It is also unclear as to the role that blast exposure history has on mTBI and PTS impairments and symptoms. The purposes of this study were to examine prospectively the effects of mTBI on neurocognitive performance as well as mTBI and PTS symptoms among US Army Special Operations Command personnel and to study the influence of history of blast mTBI on these effects. METHODS: Eighty US Army Special Operations Command personnel with (n = 19) and without (n = 61) a history of blast-related mTBI completed the military version of the Immediate Post-concussion Assessment Cognitive Test (ImPACT), Post Concussion Symptom Scale (PCSS), and the PTSD Checklist (PCL) at baseline as well as 1 day to 7 days and 8 days to 20 days following a combat-related mTBI. RESULTS: Results indicated that verbal memory (p = 0.002) and processing speed (p = 0.003) scores were significantly lower and mTBI symptoms (p = 0.001) were significantly higher at 1 day to 7 days after injury compared with both baseline and 8 days to 20 days after injury. PTS remained stable across the three periods. Participants with a history of blast mTBI demonstrated lower verbal memory at 1 day to 7 days after mTBI compared with participants without a history of blast mTBI (p = 0.02). CONCLUSION: Decreases in neurocognitive performance and increased mTBI symptoms are evident in the first 1 day to 7 days following combat-related mTBI, and a history of blast-related mTBI may influence these effects. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level II. PMID- 26131790 TI - A pilot quality improvement program to increase pediatrician injury anticipatory guidance. AB - BACKGROUND: Because of a lack of time and training, many pediatricians often address few, if any, injury topics during well-child visits. The project goal was to increase the injury anticipatory guidance topics covered by pediatricians during well-child visits by offering screening tools and focused talking points through a quality improvement learning collaborative. METHODS: Screening tools were developed and pretested. Pediatric practices, recruited through the Ohio American Academy of Pediatrics, were taught quality improvement theory and injury prevention strategies at a learning session. Pediatricians worked to implement screening tools and talking points into every well-child visit for children 1 year or younger. Monthly, providers reviewed five random charts for each of the six well-child visits for screening tool use and age-appropriate injury prevention discussion. Providers received maintenance of Certification IV credit. RESULTS: Sixteen pediatricians (six practices) participated. Screening tool use increased from 0% to 97.2% in just 3 months of the program. For each well-child care visit, injury prevention discussion increased by 89.5% for newborn visit, 88.1% for 2-month, 93.6% for 4-month, 94.0% for 6-month, 88.1% for 9-month, and 90.3% for 12-month-old babies. During the quality improvement program, discussion points for all children 1 year or younger increased for all age-appropriate topics. The greatest percent increase in discussions occurred with water safety (from 10.8% to 95.7%, n = 231), play safety (from 17.9% to 93.5%, n = 154), and supervision safety (from 20.8% to 94.4%, n = 251). More commonly addressed topics also had a significant increase in discussions: sleep safety (from 48% to 93.9%, n = 262), choking (from 44.7% to 95.4%, n = 172), and car safety (from 41.2% to 80.1%, n = 332). CONCLUSION: Participation in a maintenance of Certification IV quality improvement program within pediatric offices can increase screening and discussion of injury anticipatory guidance. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV. PMID- 26131791 TI - Automatic Adjustment of Mouse Settings to Improve Pointing Performance. AB - This article describes the development and evaluation of a software tool for the automatic configuration of mice and other pointing devices. The software is intended to accommodate the needs of people with physical impairments, with a goal of improved productivity and comfort during computer use. We successfully built prototype software that monitors user activity during performance of regular computer tasks and recommends appropriate Windows mouse settings to meet the user's specific needs. Twelve individuals with upper extremity impairments participated in an evaluation study. On average, the recommended settings significantly improved pointing performance for this subject group. The effect on trial time, entries, and error-free trials was significant at the 0.05 level. Trial time showed the strongest effect, improving by 29.3% with the settings recommended by our software. These results suggest that our software can successfully determine the appropriate mouse settings for an individual, yielding significant improvements in pointing performance. PMID- 26131792 TI - Assistive Technology(r) CEU Quiz 26.3a. PMID- 26131793 TI - Hearing Math: Algebra Supported eText for Students With Visual Impairments. AB - Supported eText for students with visual impairments in mathematics has a promising, emerging literature base, although little of the existing research focuses on implementation within a classroom setting. This qualitative study sought to understand the use of supported eText to deliver algebra to students with visual impairments enrolled in algebra mathematics courses. The study also sought to explore supported eText in contrast to students' traditional means of accessing an algebra text. The main results suggest supported eText holds potential in terms of delivering mathematics content; however, more research and more reflection on the field is needed regarding this approach as a sole means of presenting text. Implications for teacher professional development and implementation practices are discussed. PMID- 26131794 TI - Acceptance and Attitudes Toward a Human-like Socially Assistive Robot by Older Adults. AB - Recent studies have shown that cognitive and social interventions are crucial to the overall health of older adults including their psychological, cognitive, and physical well-being. However, due to the rapidly growing elderly population of the world, the resources and people to provide these interventions is lacking. Our work focuses on the use of social robotic technologies to provide person centered cognitive interventions. In this article, we investigate the acceptance and attitudes of older adults toward the human-like expressive socially assistive robot Brian 2.1 in order to determine if the robot's human-like assistive and social characteristics would promote the use of the robot as a cognitive and social interaction tool to aid with activities of daily living. The results of a robot acceptance questionnaire administered during a robot demonstration session with a group of 46 elderly adults showed that the majority of the individuals had positive attitudes toward the socially assistive robot and its intended applications. PMID- 26131795 TI - Effects of Wheelchair Seat-height Settings on Alternating Lower Limb Propulsion With Both Legs. AB - This study investigated the effects of seat-height settings of wheelchairs with alternating propulsion with both legs. Seven healthy individuals with no orthopedic disease participated. Flexion angles at initial contact (FA-IC) of each joint, range of motion during propulsion period (ROM-PP), and ground reaction force (GRF) were measured using a three dimensional motion capture system and force plates, and compared with different seat-height settings. Statistically significant relationships were found between seat-height and speed, stride length, knee FA-IC, ankle FA-IC, hip ROM-PP, vertical ground reaction force (VGRF), and anterior posterior ground reaction force (APGRF). Speed, hip ROM-PP, VGRF and APGRF increased as the seat-height was lowered. This effect diminished when the seat-height was set below -40 mm. VGRF increased as the seat height was lowered. The results suggest that the seat-height effect can be attributed to hip ROM-PP; therefore, optimal foot propulsion cannot be achieved when the seat height is set either too high or too low. Efficient foot propulsion of the wheelchair can be achieved by setting the seat height to lower leg length according to a combination of physical characteristics, such as the user's physical functions, leg muscles, and range of motion. PMID- 26131796 TI - An Investigation Into the Measurement and Prediction of Mechanical Stiffness of Lower Limb Prostheses Used for Running. AB - Two energy return prosthesis are subjected to three different statically applied loading methods. This initial study proposes that statically applied loading to a sport prosthesis using several controlled methods were statistically robust enough to derive a mechanical stiffness value. However, any predicted stiffness is drawn into question when allowing any movement of the distal end. This uncertainty will make any evaluation or prescription of lower limb prosthesis technology based upon their stiffness incorrect. In addition, the peak calculated stiffness at the expected bodyweight induced ground impact load of a runner is judged the most representative assessment method. This study attempts to build on previous research advocating the need to monitor the performance of prosthesis lower limb technology in disability sport. PMID- 26131797 TI - Investigating the International Classification of Functioning, Disability, and Health (ICF) Framework to Capture User Needs in the Concept Stage of Rehabilitation Technology Development. AB - This study evaluates whether the International Classification of Functioning, Disability, and Health (ICF) framework provides a useful basis to ensure that key user needs are identified in the development of a home-based arm rehabilitation system for stroke patients. Using a qualitative approach, nine people with residual arm weakness after stroke and six healthcare professionals with expertise in stroke rehabilitation were enrolled in the user-centered design process. They were asked, through semi-structured interviews, to define the needs and specification for a potential home-based rehabilitation device to facilitate self-managed arm exercise. The topic list for the interviews was derived by brainstorming ideas within the clinical and engineering multidisciplinary research team based on previous experience and existing literature in user centered design. Meaningful concepts were extracted from questions and responses of these interviews. These concepts obtained were matched to the categories within the ICF comprehensive core set for stroke using ICF linking rules. Most of the concepts extracted from the interviews matched to the existing ICF Core Set categories. Person factors like gender, age, interest, compliance, motivation, choice, and convenience that might determine device usability are yet to be categorized within the ICF comprehensive core set. The results suggest that the categories of the comprehensive ICF Core Set for stroke provide a useful basis for structuring interviews to identify most users needs. However some personal factors (related to end users and healthcare professionals) need to be considered in addition to the ICF categories. PMID- 26131798 TI - A Clinical Parameters-Based Model Predicts Anastomotic Leakage After a Laparoscopic Total Mesorectal Excision: A Large Study With Data From China. AB - Anastomotic leakage after colorectal surgery is a major and life-threatening complication that occurs more frequently than expected. Intraoperative judgment in predicting potential leakage has shown extremely low sensitivity and specificity. The lack of a model for predicting anastomotic leakage might explain this insufficient judgment. We aimed to propose a clinical parameters-based model to predict anastomotic leakage after laparoscopic total mesorectal excision (TME).This study was a retrospective analysis of a prospectively designed colorectal cancer dataset. In total, 1968 patients with a laparoscopic TME were enrolled from November 1, 2010, to March 20, 2014. The independent risk factors for anastomotic leakage were identified, from which the parameters-based model for leakage was developed.Anastomotic leakage was noted in 63 patients (3.2%). Male sex, a low level of anastomosis, intraoperative blood loss, diabetes, the duration time of the surgery, and low temperature were significantly associated by the bivariate analysis and the Cochran-Mantel-Haenszel test with an increased risk. From these factors, the logistic regression model identified the following 4 independent predictors: male sex (risk ratio [RR] = 1.85, 95% confidence interval [CI]: 1.13-4.87), diabetes (RR = 2.08, 95% CI: 1.19-5.8), a lower anastomosis level (RR = 3.41, 95% CI: 1.17-6.71), and a high volume of blood loss (RR = 1.03, 95% CI: 1.01-1.05). The locally weighted scatterplot smoothing regression showed an anastomosis within 5 cm from the anus and intraoperative blood loss of >100 mL as the cutoff values for a significantly increased risk of leakage. Based on these independent factors, a parameters-based model was established by the regression coefficients. The high and low-risk groups were classified according to scores of 3-5 and 0-2, with leakage rates of 8.57% and 1.66%, respectively (P < 0.001).This parameters-based model could predict the risk of anastomotic leakage following laparoscopic rectal cancer. After further validation, this model might facilitate the intraoperative recognition of high risk patients to perform defunctional stomas. PMID- 26131799 TI - Phase II Trial of Goserelin and Exemestane Combination Therapy in Premenopausal Women With Locally Advanced or Metastatic Breast Cancer. AB - A promising option as the treatment of choice for premenopausal patients with locally advanced or metastatic breast cancer (MBC) could be the combination of a luteinizing hormone-releasing hormone analog and an aromatase inhibitor. However, no prospective studies on the efficacy of goserelin with exemestane in locally advanced or MBC premenopausal breast cancer patients have been reported.We present the phase II trial of goserelin plus exemestane in a total of 44 premenopausal women with locally advanced or MBC. All patients received a subcutaneous injection of 3.6 mg goserelin every 4 weeks along with 25 mg exemestane daily. The primary end point was progression-free survival (PFS). The second end point included overall survival (OS), objective response rate (ORR), duration of response (DOR), and clinical benefit rate (CBR) based on complete response (CR), partial response (PR), or stable disease (SD) for >=6 months.The median PFS was 13 months (range: 2-42 months). The median DOR was 8 months (range: 2-40 months). Two patients achieved CR (4.5%), and 15 patients experienced PR (34.1%). Fifteen patients (34.1%) had SD >=6 months. The ORR was 38.6%, and the CBR was 65.9%. Primary progressive disease occurred in 15 patients (34.1%). Five patients (11.4%) died during the study period. Because a few patients have died, the median OS has not been reached. Drug therapy was well tolerated. The most frequent grade-3 adverse events were arthralgia (18.2%), skin rash (6.8%), and myalgia (4.5%). No participants withdrew from the study due to drug toxicity.This study suggested that goserelin and exemestane might be highly effective and well-tolerated regimens in premenopausal women with hormone responsive, locally advanced or MBC. PMID- 26131800 TI - Dose-Effectiveness Relationships Determining the Efficacy of Ibandronate for Management of Osteoporosis: A Meta-Analysis. AB - The purpose of this study was to perform a meta-analysis on the efficacy of ibandronate by evaluating the effect sizes of different dosing regimens.Major electronic databases were searched from 1985 to February 2015. A random effects meta-analysis was performed in STATA.Data from 34 studies (13,639 patients) were included in this meta-analysis. Ibandronate treatment significantly improved lumbar spine bone mineral density (BMD) as shown by the percent change from baseline (4.80%, P < 0.0001, 95% confidence interval [CI] [4.14, 5.45]). The respective effect sizes for oral intake and intravenous (IV) infusion were 4.57% and 5.22% (P < 0.0001, CIs [3.71, 5.42] and [4.37, 6.07]), respectively. All doses led to a significant increase in BMD except 2 oral dose regimens (1 mg/d: 4.65%, P = 0.285, 95% CI [-3.87, 13.18] and 0.5 mg/d: 3.60%, P = 0.38, 95% CI [ 4.43, 11.64]. Ibandronate treatment (overall as well as dose wise) also significantly improved the total hip BMD-2.30% overall, 2.13% oral, and 2.63% IV (P < 0.0001, 95% CIs [1.96, 2.64], [1.70, 2.55], and [2.07, 3.20]), respectively. Ibandronate administration significantly decreased serum markers of bone resorption to -46.53% for C-terminal telopeptide of type 1 collagen, -24.03% for bone-specific alkaline phosphatase, and -50.17% for procollagen type I N-terminal propeptide (P < 0.0001, 95% CIs [-53.16, -39.91], [-31.28, -16.77], and [-64.13, 36.20]), respectively. Parathyroid hormone levels remained unaffected by ibandronate treatment (3.03%, P = 0.439, 95% CI [-5.06, 11.66]).There was no significant difference in the efficacy of ibandronate between oral or IV administration. Predominant dose regimens for IV administration were 1 to 3 mg/3 mo and 150 mg/mo oral and 2.5 mg/d for oral ibandronate treatment. PMID- 26131801 TI - Survival Benefits of Western and Traditional Chinese Medicine Treatment for Patients With Pancreatic Cancer. AB - Traditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with cancer worldwide. However, the clinical effect of TCM on patients with pancreatic cancer remains unclear. This study was aimed to explore the efficacy of TCM on selected patients with pancreatic cancer and to study the usefulness of multimodality treatment, including TCM and western medicine (WM), in pancreatic cancer.From January 2009 to October 2013, 107 patients with pancreatic cancer were included in this study. Kaplan-Meier curves were used to assess the differences in survival time. Cox regression analysis was performed to determine survival trends adjusted for clinical and demographic factors.Cox regression analysis suggested that elevated CA19-9 levels (P = 0.048), number of cycles of chemotherapy (P = 0.014), and TCM were independent prognostic factors (P < 0.001). The survival hazards ratio of TCM was 0.419 (95% confidence interval [CI], 0.261-0.671). The median overall survival (OS) was 19 months for patients with TCM treatment, while the median OS was 8 months for those without TCM treatment (P < 0.001). Patients who received multimodality treatment using TCM and WM had the best prognosis with a median OS of 19 months (P < 0.001). Patients with heat-clearing, diuresis-promoting and detoxification TCM treatment had a longer survival time (32.4 months) than those with blood-activating and stasis-dissolving (9.8 months) and tonifying qi and yang treatment (6.1 months; P = 0.008).These results indicate that TCM has an important potential value for improving the prognosis of patients with pancreatic cancer, and multimodality treatment, including TCM and WM, leads to the best prognosis. More importantly, we suggest that heat-clearing, diuresis-promoting, and detoxification TCM treatment may improve the efficacy of TCM in pancreatic cancer. PMID- 26131802 TI - Developing Shingles-Induced Koebner Phenomenon in a Patient With Psoriasis: A Case Report. AB - Both shingles and psoriasis are common cutaneous diseases. About 25% of the psoriatic patients develop Koebner phenomenon (KP) after various injuries, and in rare instance, KP may occur at the site of healed or healing shingles.We report a 30-year-old man with 7-month history of scalp psoriasis who developed KP at the areas of developing shingles. Cutaneous examination revealed scaly erythematous papules and plaques located on the scalp and forehead, and groups of clustered erythematous papules with silver scales in the dermatome distributed on the right side of chest wall the prior herpes zoster lesions involved. After removal of the scales on the papules, underlying bleeding points were present.The lesions on chest had good response to anti-psoriatic therapies, as the lesions on scalp did. After a year of follow-up, recurrent psoriasis occurred, but the lesions were located only on the scalp, and the areas of prior occurrence of shingles, because of which we considered diagnosis of recurrent psoriasis rather than relapsing KP for the chest lesions.Not only the healing and healed shingles can trigger KP in psoriasis, but also the developing shingles can cause psoriatic KP at the site of herpes zoster lesions. PMID- 26131803 TI - Diagnosis of Iron Deficiency in Inflammatory Bowel Disease by Transferrin Receptor-Ferritin Index. AB - Iron deficiency is common in patients with inflammatory bowel disease (IBD), but can be difficult to diagnose in the presence of inflammation because ferritin is an acute phase reactant. The transferrin receptor-ferritin index (TfR-F) has a high sensitivity and specificity for iron deficiency diagnosis in chronic diseases. The diagnostic efficacy of TfR-F is little known in patients with IBD. The aim of the study was to assess the added value of TfR-F to iron deficiency diagnosis in a prospective cohort of patients with IBD.Consecutive IBD patients were prospectively enrolled. Patients were excluded in case of blood transfusion, iron supplementation, or lack of consent. IBD activity was assessed on markers of inflammation (C-reactive protein, endoscopy, fecal calprotectin). Hemoglobin, ferritin, vitamin B9 and B12, Lactate dehydrogenase, haptoglobin, and soluble transferrin receptor (sTfR) were assayed. TfR-F was calculated as the ratio sTfR/log ferritin. Iron deficiency was defined by ferritin <30 ng/mL or TfR-F >2 in the presence of inflammation.One-hundred fifty patients with median age 38 years (16-78) and Crohn disease (n = 105), ulcerative colitis (n = 43), or unclassified colitis (n = 2) were included. Active disease was identified in 45.3%. Anemia was diagnosed in 28%. Thirty-six patients (24%) had ferritin <30 ng/mL. Thirty-two patients (21.3%) had ferritin levels from 30 to 100 ng/ml and inflammation: 2 had vitamin B12 deficiency excluding TfR-F analysis, 13 of 30 (43.3%) had TfR-F >2. Overall, iron deficiency was diagnosed in 32.7% of the patients.TfR-F in addition to ferritin <30 ng/mL criterion increased by 36% diagnosis rates of iron deficiency. TfR-F appeared as a useful biomarker that could help physicians to diagnose true iron deficiency in patients with active IBD. PMID- 26131804 TI - Incidentally Visualization of the Thymus on Whole-Body Iodine Scintigraphy: Report of 2 Cases and Review of the Latest Insights. AB - Radioiodine uptake is not commonly seen by the thymus gland. On the contrary, the gland is slowly replaced by fat after puberty. Herein, we present 2 patients with papillary thyroid carcinoma, follicular variant, and cervical lymph node involvement. After total/near-total thyroidectomy, the patients received I for ablation therapy. On posttreatment radioiodine scintigraphy, mediastinal I uptake was noted that finally was histologically/anatomically diagnosed as thymus gland uptake. It should be borne in mind as a potential cause of false-positive whole body I scintigraphy. PMID- 26131805 TI - Cutaneous Invasive Aspergillosis: Retrospective Multicenter Study of the French Invasive-Aspergillosis Registry and Literature Review. AB - Invasive aspergillosis (IA) has poor prognosis in immunocompromised patients. Skin manifestations, when present, should contribute to an early diagnosis. The authors aimed to provide prevalence data and a clinical and histologic description of cutaneous manifestations of primary cutaneous IA (PCIA) and secondary CIA (SCIA) in a unique clinical series of IA and present the results of an exhaustive literature review of CIA. Cases of proven and probable IA with cutaneous manifestations were retrospectively extracted from those registered between 2005 and 2010 in a prospective multicenter aspergillosis database held by the National Reference Center for Invasive Mycoses and Antifungals, Pasteur Institute, France. Patients were classified as having PCIA (i.e., CIA without extracutaneous manifestations) or SCIA (i.e., disseminated IA). Among the 1,410 patients with proven or probable IA, 15 had CIA (1.06%), 5 PCIA, and 10 SCIA. Hematological malignancies were the main underlying condition (12/15). Patients with PCIA presented infiltrated and/or suppurative lesions of various localizations not related to a catheter site (4/5), whereas SCIA was mainly characterized by disseminated papules and nodules but sometimes isolated nodules or cellulitis. Histologic data were available for 11 patients, and for 9, similar for PCIA and SCIA, showed a dense dermal polymorphic inflammatory infiltrate, with the epidermis altered in PCIA only. Periodic acid Schiff and Gomori-Grocott methenamine silver nitrate staining for all but 2 biopsies revealed hyphae compatible with Aspergillus. Aspergillus flavus was isolated in all cases of PCIA, with Aspergillus fumigatus being the most frequent species (6/10) in SCIA. Two out 5 PCIA cases were treated surgically. The 3-month survival rate was 100% and 30% for PCIA and SCIA, respectively. Our study is the largest adult series of CIA and provides complete clinical and histologic data for the disease. Primary cutaneous IA should be recognized early, and cases of extensive necrosis should be treated surgically; its prognosis markedly differs from that for SCIA. Any suppurative, necrotic, papulonodular, or infiltrated skin lesion in an immunocompromised patient should lead to immediate biopsy for histologic analysis and mycological skin direct examination and culture. PMID- 26131806 TI - Effect of 23-Valent Pneumococcal Polysaccharide Vaccine Inoculated During Anti Cancer Treatment Period in Elderly Lung Cancer Patients on Community-Acquired Pneumonia Hospitalization: A Nationwide Population-Based Cohort Study. AB - To evaluate effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) inoculated during defined "vaccination period," first 6 months post cancer diagnosis (ie, an anti-cancer treatment period), in elderly lung cancer patients on community-acquired pneumonia (CAP) hospitalization incidence.This was a nationwide population-based cohort study of 157 newly diagnosed elderly lung cancer patients receiving PPSV23 during "vaccination period", and 628 age and sex one-to-one matched controls enrolled in the National Health Insurance Research Database (NHIRD) of Taiwan between 2007 and 2010. All patients were >=75 years old and still survival post "vaccination period." Incidence density (ID) of all cause inpatient CAP and cumulative survival risk were analyzed by multivariate Poisson regression and Kaplan-Meier method, respectively.After a 4-year follow up, IDs of all-cause inpatient CAP for vaccination and control cohorts were 297 and 444 per 1000 PYs, respectively. Less vaccinated patients had CAP incidence density >1 time per PY (12.7% vs 21.2%) than non-vaccinated patients. After adjusting for potential confounding variables, like influenza vaccination, comorbidities, cancer treatment modalities, and socioeconomic status, adjusted inpatient CAP incidence rate in PPSV23 vaccination cohort was 0.74 times lower than control cohort (incidence rate ratio [IRR] = 0.740, P = 0.0339). Two-year cumulative CAP hospitalization rates and overall survival rates were 37.1% vs. 55.4%, and 46.6% vs. 26.2%, respectively, for lung cancer patients with and without PPSV23 (both P < 0.001). Subgroup analysis showed that for elderly lung cancer patients not ever receiving influenza vaccine, PPSV23 still had trend to reduce all-cause inpatient CAP.For elderly lung cancer patients aged >=75 years, PPSV23 inoculated during anti-cancer treatment period could reduce CAP hospitalizations and improve survival. PMID- 26131807 TI - Phakomatosis Pigmentovascularis Associated With Sturge-Weber Syndrome, Ota Nevus, and Congenital Glaucoma. AB - Phakomatosis pigmentovascularis (PPV) is a rare congenital malformation syndrome that is characterized by a combination of capillary abnormalities and dermal melanocytosis.We describe 3 cases of PPV combined with bilateral Sturge-Weber syndrome (SWS), Ota nevus, and congenital glaucoma.Case 1 was a 2-year-old boy. Facial port-wine stains distributed along the 3 branches of his trigeminal nerves, which suggested the existence of SWS. Gray-blue patches were spread over the frontal and temporal areas of bilateral face, waist, buttocks, and thigh. Bilateral triangular alopecia was found on the temporal scalp. The diagnosis of Ota nevus was made by the bilateral scleral malanocystosis. Increased intraocular pressure, enlarged cornea, and pathologic optic disc cupping supported the diagnoses of infantile bilateral glaucoma. Case 2 was a 4-year-old boy. Port-wine stains were found on the face along the 3 branches of the trigeminal nerve and distributed along the trunk, arms, and legs. Mongolian spots spread over his frontal and temporal areas of the bilateral face, waist, buttocks, thigh, abdomen, and back. Infantile glaucoma was found in both eyes. Ota nevus were found in the both eyes. Optic coherent tomography (OCT) scans revealed increased thickness of choroid. Case 3 was a 5-year-old boy. Besides Ota nevus and infantile glaucoma in both eyes, color Doppler ultrasonography showed choroidal hemagioma. OCT scan showed increased choroidal thickness. The bilateral triangular alopecia on the child's temporal scalp was similar to that of Case 1. Cases 1 and 2 presented with port-wine stain patches that were consistent with the characteristic manifestation of PPV type IIb. However, the CMTC of Case 3 met the diagnostic criteria for PPV type Vb.Case 1 was treated with trabeculotomies in both eyes. For Cases 2 and 3, surgical interventions were not considered due to the high risks of antiglaucomatous operation complications. We prescribed them antiglaucoma indications.The simultaneously coexistence of PPV with SWS, Ota nevus, and congenital glaucoma is rare. In the clinic, additional detailed examinations and tests of PPV patients to exclude other ocular abnormalities or extraocular involvements are necessary. PMID- 26131809 TI - Anti-NMDA Receptor Encephalitis During Pregnancy: A Case Report. AB - Anti-N-methyl-D-aspartate receptor (anti-MMDAR) encephalitis is an immune mediated encephalitis mainly affecting young women.We describe the case of a 21 year-old woman who developed a classical form of anti-NMDAR encephalitis during the 10th week of gestation. The patient had been treated with methylpredinsolone and intravenous immunoglobulins. Birth history of the child was normal, with normal APGAR score. The clinical symptoms of the patient have improved after a few months.This rare occurrence during pregnancy (only 9 other cases described) presents an opportunity to highlight the importance of making the earliest possible diagnosis of this treatable and potentially reversible encephalitis, and to educate gynecologists, psychiatrists, anesthetists, and neurologists on this potential cause of psychiatric and neurological manifestations during pregnancy. PMID- 26131808 TI - Association Between Vascular Access Dysfunction and Subsequent Major Adverse Cardiovascular Events in Patients on Hemodialysis: A Population-Based Nested Case Control Study. AB - The association between dialysis vascular access dysfunction and the risk of developing major adverse cardiovascular events (MACE) in hemodialysis patients is unclear and has not yet been investigated. We analyzed data from the National Health Insurance Research Database of Taiwan to quantify this association. Adopting a case-control design nested within a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9711 incident cases of MACE during the stage of stable maintenance dialysis and 19,422 randomly selected controls matched to cases on age, gender, and duration of dialysis. Events of vascular access dysfunction in the 6-month period before the date of MACE onset (ie, index date) for cases and before index dates for controls were evaluated retrospectively. The presence of vascular access dysfunction was associated with a 1.385-fold higher odds of developing MACE as estimated from the logistic regression analysis. This represents a significantly increased adjusted odds ratio (OR) at 1.268 (95% confidence interval [CI] = 1.186-1.355) after adjustment for comorbidities and calendar years of initiating dialysis. We also noted a significant exposure-response trend (P < 0.001) between the frequency of vascular access dysfunction and MACE, with the greatest risk (adjusted OR = 1.840, 95% CI = 1.549-2.186) noted in patients with >=3 vascular access events. We concluded that dialysis vascular access dysfunction was significantly associated with an increased risk of MACE. Hence, vascular access failure can be an early sign for MACE in patients receiving maintenance hemodialysis. Active monitoring and treatment of cardiovascular risk factors and related diseases, not merely managing vascular access dysfunction, would be required to reduce the risk of MACE. PMID- 26131810 TI - The Association of Hematological Malignancy and End-of-Life Expenditure in Cancer Decedents: A Population-Based Study in an Asian Country. AB - Within the overall National Health Insurance (NHI) budget in Taiwan, there has been a remarkable increase in expenditure for cancer patients. This study was designed to explore whether hematological malignancy is associated with higher end-of-life (EOL) medical expenditure in their last 6 months of life.We used data from the Taiwan NHI Research Database to do a retrospective cohort and population based study. There were 42,754 cancer patients enrolled in order to study the determinants of medical expenditure for EOL care from 2009 to 2011.The mean medical expenditure for EOL care for cancer patients in the last 6 months of life was $12,965 +/- 10,959 (mean +/- standard deviation ) (all costs are given in US dollars). Patients with acute leukemia and lymphoma had an additional cost of $16,934 and $7840 than those with nonhematological malignancy (P < 0.001). Medical expenditures for cancer patients with a hematological malignancy and postdiagnosis survival of >6 months, between 6 and 12 months, and >12 months all showed that acute leukemia and lymphoma accounted for more medical expenditure than did others (P < 0.001). The primary physician's specialty between acute leukemia, lymphoma, and nonhematological malignancy patients had statistically difference.The medical expenditure of cancer patients in acute leukemia and lymphoma was more than nonhematological malignancy. Treatment strategies for acute leukemia should be studied further in order to save the health care budget. PMID- 26131811 TI - Preoperative Standardized Uptake Value of Metastatic Lymph Nodes Measured by 18F FDG PET/CT Improves the Prediction of Prognosis in Gastric Cancer. AB - This study assessed whether preoperative maximum standardized uptake value (SUVmax) of metastatic lymph nodes (LNs) measured by F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) could improve the prediction of prognosis in gastric cancer.One hundred fifty-one patients with gastric cancer and pathologically confirmed LN involvement who had undergone preoperative F-FDG PET/CT prior to curative surgical resection were retrospectively enrolled. To obtain nodal SUVmax, a transaxial image representing the highest F-FDG uptake was carefully selected, and a region of interest was manually drawn on the highest F-FDG accumulating LN. Conventional prognostic parameters and PET findings (primary tumor and nodal SUVmax) were analyzed for prediction of recurrence-free survival (RFS) and overall survival (OS). Furthermore, prognostic accuracy of survival models was assessed using c statistics.Of the 151 patients, 38 (25%) experienced recurrence and 34 (23%) died during follow-up (median follow-up, 48 months; range, 5-74 months). Twenty-seven patients (18%) showed positive F-FDG nodal uptake (range, 2.0-22.6). In these 27 patients, a receiver-operating characteristic curve demonstrated a nodal SUVmax of 2.8 to be the optimal cutoff for predicting RFS and OS. The univariate and multivariate analyses showed that nodal SUVmax (hazard ratio [HR] = 2.71, P < 0.0001), pathologic N (pN) stage (HR = 2.58, P = 0.0058), and pathologic T (pT) stage (HR = 1.77, P = 0.0191) were independent prognostic factors for RFS. Also, nodal SUVmax (HR = 2.80, P < 0.0001) and pN stage (HR = 2.28, P = 0.0222) were independent prognostic factors for OS. A predictive survival model incorporating conventional risk factors (pT/pN stage) gave a c-statistic of 0.833 for RFS and 0.827 for OS, whereas a model combination of nodal SUVmax with pT/pN stage gave a c-statistic of 0.871 for RFS (P = 0.0355) and 0.877 for OS (P = 0.0313).Nodal SUVmax measured by preoperative F-FDG PET/CT is an independent prognostic factor for RFS and OS. Combining nodal SUVmax with pT/pN staging can improve survival prediction precision in patients with gastric cancer. PMID- 26131812 TI - Subcapsular Hepatic Hematoma After Endoscopic Retrograde Cholangiopancreatography: A Case Report and Review of Literature. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most frequently performed procedures for the diagnosis and treatment of biliary pancreatic diseases. ERCP-related complications total around 2.5% to 8%, with a mortality rate ranging from 0.5% to 1%. An exceptional ERCP complication is subcapsular hepatic hematoma, and few cases are reported worldwide.We present the case of a 52-year-old woman with a history of recurring upper abdominal pain and a clinical and ultrasonographic diagnosis of obstructive jaundice due to common bile duct stones. After 2 difficult endoscopic biliary procedures, common bile duct stones clearance was obtained. Post-ERCP course was symptomatic with upper abdominal pain and anemization with hemodynamic instability.CT scan demonstrated a 15 cm * 11 cm subcapsular hepatic hematoma filled with air and liquid on the surface of the right hepatic lobe. The patient was successfully treated with the embolization of a small branch of right hepatic artery angiographically identified as the cause of bleeding.Subcapsular hepatic hematoma after ERCP is a rare complication that must be taken into account in the differential diagnosis of symptomatic cases after ERCP. Its diagnosis is based on clinical and laboratory data and especially on imaging (ultrasound, CT, or MRI). Treatment is often conservative but, in some cases, embolization or percutaneous drainage or surgery may be necessary. PMID- 26131813 TI - Risk Factors Associated With Residual Stones in Common Bile Duct Via T Tube Cholangiography After Common Bile Duct Exploration. AB - Open surgery with common bile duct (CBD) exploration and T tube drainage are still traditionally performed in a large amount of selected patients with cholelithiasis and choledocholithiasis. Confirmation of CBD clearance via T tube cholangiography after surgery is a routine procedure before T tube removal. The present study aims at investigating potential risk factors associated with residual stones in CBD via T tube cholangiography.Patients undergoing open CBD exploration and T tube drainage for choledocholithiasis in the hospital were enrolled retrospectively from January 2011 to December 2013. The clinical data were reviewed and analyzed based on computer database. Patients undergoing laparoscopic CBD exploration were excluded. Patients with CBD exploration and primary choledochotomy or choledochojejunostomy were also excluded from the study. T tube cholangiography was regularly performed 4 to 8 weeks postoperatively.Two hundred seventy-five patients undergoing open CBD exploration and T tube drainage were enrolled in the study. Thirty-five patients (12.7%) were found to have gallbladder stones but without bile duct stones intraoperatively (Group A). One hundred sixty-five (Group B) and 77 patients (Group C) were diagnosed with choledocholithiasis and hepato-choledocholithiasis in operation, respectively. Disease of hepato-choledocholithiasis, size of the previous stones, and CBD exploration without intraoperative choledochoscopy were identified as risk factors associated with residue stones via T tube cholangiography (P < 0.001, P = 0.034, and P = 0.047, respectively). Patients with residual stones had a higher incidence of cholangitis during cholangiography than those without residual stones (8.9% vs 7.8%, P = 0.05). A scoring system based on the 3 risk factors has been set up. The incidence of residual stones were 5.6% in patients with score 0 to 1, 27.4% in patients with score 2 to 3 and 80.0% in patients with score 4 (P < 0.001). Abdominal distension after T tube clamp might be a strong predictor of cholangiography-associated choloangitis (P < 0.001). Intraopearative choledochoscopy should be strongly recommended as a routine procedure during CBD exploration to confirm the clearance of CBD, which could significantly lower the risk of residual stones postoperatively. PMID- 26131814 TI - Quantification of Pulmonary Inflammatory Processes Using Chest Radiography: Tuberculosis as the Motivating Application. AB - The purpose of this work was to develop a quantitative method for evaluating the pulmonary inflammatory process (PIP) through the computational analysis of chest radiography exams in posteroanterior (PA) and lateral views. The quantification procedure was applied to patients with tuberculosis (TB) as the motivating application.A study of high-resolution computed tomography (HRCT) examinations of patients with TB was developed to establish a relation between the inflammatory process and the signal difference-to-noise ratio (SDNR) measured in the PA projection. A phantom essay was used to validate this relation, which was implemented using an algorithm that is able to estimate the volume of the inflammatory region based solely on SDNR values in the chest radiographs of patients.The PIP volumes that were quantified for 30 patients with TB were used for comparisons with direct HRCT analysis for the same patient. The Bland-Altman statistical analyses showed no significant differences between the 2 quantification methods. The linear regression line had a correlation coefficient of R = 0.97 and P < 0.001, showing a strong association between the volume that was determined by our evaluation method and the results obtained by direct HRCT scan analysis.Since the diagnosis and follow-up of patients with TB is commonly performed using X-rays exams, the method developed herein can be considered an adequate tool for quantifying the PIP with a lower patient radiation dose and lower institutional cost. Although we used patients with TB for the application of the method, this method may be used for other pulmonary diseases characterized by a PIP. PMID- 26131815 TI - Investigation of Gastroduodenal Mucosal Injury in Japanese Asymptomatic Antiplatelet Drug Users. AB - Antiplatelet drugs are widely used for the prevention of cardiovascular disease and cerebral vascular disorders. Although there have been several studies on gastroduodenal mucosal injury with gastrointestinal (GI) symptoms such as GI bleeding, in antiplatelet drug users (including low-dose aspirin (LDA)), there have been few reports on the association between antiplatelet drug use and gastroduodenal mucosal injury in asymptomatic antiplatelet drug users. This study was a cross-sectional study elucidating the association between antiplatelet drug use and gastroduodenal mucosal injury in asymptomatic antiplatelet drug users.Subjects were 186 asymptomatic Japanese antiplatelet drug users who underwent a regular health checkup. Subjects were divided into those with and without gastroduodenal mucosal injury endoscopically, and the association between gastroduodenal mucosal injury and other data in asymptomatic antiplatelet drug users was investigated.The prevalence of males and drinkers were significantly higher in subjects with gastroduodenal mucosal injury than in those without. In addition, the prevalence of proton pump inhibitor (PPI) users was significantly lower in subjects with gastroduodenal mucosal injury than in subjects without gastroduodenal mucosal injury. Logistic regression analysis showed PPI (odds ratios: 0.116; 95% confidence intervals: 0.021-0.638; P < 0.05) was a significant predictor of a decreased prevalence of gastroduodenal mucosal injury and closed type (C-type) atrophy (3.172; 1.322-7.609; P < 0.01) was a significant predictor of an increased prevalence of severe gastroduodenal mucosal injury in asymptomatic antiplatelet drug users.Gender and lifestyle, such as drinking, may have an impact on risk of gastroduodenal mucosal injury in asymptomatic subjects taking antiplatelet drugs. Although PPI is a significant predictor of a decreased prevalence of gastroduodenal mucosal injury, including in asymptomatic antiplatelet drug users, status of gastric atrophy should also be considered against severe gastroduodenal mucosal injury. PMID- 26131816 TI - High ERalpha36 Expression Level and Membrane Location Predict Poor Prognosis in Renal Cell Carcinoma. AB - Estrogen receptor alpha 36 (ERalpha36), a truncated variant of ERalpha, is located in cytoplasm and membrane that is different from other nuclear receptors of ERalpha family. ERalpha36 is involved in progression and treatment resistance of a variety of carcinomas. However, the clinical and prognostic significance of ERalpha36 in renal tumors have not been fully elucidated.Here, renal tumor tissues from 125 patients were collected and immunohistochemical stained with ERalpha36 antibody. ERalpha36 expression level and location in these cases were analyzed for their correlations with clinical characteristics. The differential diagnosis value was also assessed for benign and malignant renal tumors, as well as its prognostic value.The results showed that membrane ERalpha36 expression was rarely detected in benign tumors but predominantly observed in malignant renal tumors. Kaplan-Meier analysis indicated that significant correlations of high ERalpha36 level and ERalpha36 membrane expression were correlated with both poor disease-free survival and overall survival. Univariate and multivariate analysis confirmed that both ERalpha36 high expression and membrane location can serve as unfavorable prognostic indicators for renal cell carcinoma.It is thus concluded that membrane ERalpha36 expression is valuable for differential diagnosis of malignant renal tumors from benign ones. Both ERalpha36 high expression and membrane location indicate poor prognosis in renal cell carcinoma. PMID- 26131817 TI - T-Helper Type 9 Cells Play a Central Role in the Pathogenesis of Respiratory Epithelial Adenomatoid Hamartoma. AB - The etiology and pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) remain poorly understood, although some reports have suggested that REAH features an inflammatory process. T-helper type 9 (Th9) cells are a newly identified subset of CD4 T-helper cells characterized by the expression of high levels of interleukin (IL)-9, which may promote inflammation. As REAH may involve an inflammatory process, we evaluated whether IL-9 and/or Th9 cells were present in REAH and compared the levels thereof to those of normal nasal mucosa. Eleven patients with REAH and 5 exhibiting cerebrospinal fluid leakage were included in the study. Flow cytometry was used to measure Th9 cell numbers, a cytometric bead assay was applied to measure IL-9 levels, and real-time polymerase chain reaction was used to quantify the levels of mRNA encoding IL-9. Th9 cells, IL-9 mRNA, and IL-9 were detected in all REAH and control samples. The proportion of Th9 cells in the patients with REAH was significantly greater than that in the controls. The expression levels of IL-9-encoding mRNA and IL-9 protein were significantly higher in the patients with REAH than in the controls. The Th9 cell subset was expanded, the synthesis of IL-9-encoding mRNA was upregulated, and IL-9 secretion was increased in REAH tissue, suggesting that Th9 cells play a central role in the pathogenesis of the disease. PMID- 26131818 TI - Treatment of Adults With Treatment-Resistant Depression: Electroconvulsive Therapy Plus Antidepressant or Electroconvulsive Therapy Alone? Evidence From an Indirect Comparison Meta-Analysis. AB - Electroconvulsive therapy (ECT) and antidepressant are the effective treatment alternatives for patients with treatment-resistant depression (TRD); however, the effects and safety of the ECT plus antidepressant relative to ECT alone remain controversial. We decide to assess the potential of ECT plus antidepressant compared with ECT alone by undertaking an indirect comparison meta analysis.Databases from PubMed, ISI Web of Science, CENTRAL, Clinicaltrials.gov, EMBASE, CBM (China Biomediccal Literatures Database), and CNKI (China National Knowledge Infrastructure) were searched for relevant studies through November 21, 2014. Literature was screened, data were extracted and methodological quality of the eligible trial was assessed by 2 independent reviewers accordingly. Then, head-to-head and indirect comparison meta-analyses were carried out.A total of 17 studies which including 13 studies regarding ECT plus antidepressant versus antidepressant alone and 4 studies concerning ECT versus antidepressant alone containing a total of 1098 patients were incorporated into this meta-analysis. The head-to-head comparison suggested that response rate can be improved in the ECT plus antidepressant (RR, 1.82; 95% CI, 1.55-2.14) and ECT alone group (RR, 2.24, 95% CI, 1.51-3.33) compared with antidepressant alone, respectively; adverse complications including memory deterioration and somatization were not significantly increased except incidence of memory deterioration in ECT plus antidepressant in the 4th weeks after treatment (RR, 0.09, 95% CI, 0.02-0.49). Indirect comparison meta-analysis showed that no significant differences were detected in response rate and memory deterioration between ECT plus antidepressant and ECT alone. However, ECT plus antidepressant increased the incidence of memory deterioration relative to ECT alone.With present evidence, the regime of ECT plus antidepressant should not be preferentially recommended to treat the patients with TRD relative to ECT alone. PMID- 26131819 TI - The Impact of Diabetes Mellitus on Renal Cell Carcinoma Prognosis: A Meta Analysis of Cohort Studies. AB - Previous studies that investigated the relationship between DM and survival in renal cell carcinoma (RCC) patients reported inconsistent findings. Hence, we conducted a meta-analysis to obtain a more precise evaluation of the prognostic significance of DM in RCC. A systematic review was conducted with PubMed, Embase, and Web of Science to identify relevant articles that evaluated the effect of DM on RCC patients. Based on the inclusion and quality assessment criteria, 18 studies were eligible for the meta-analysis. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for overall survival (OS), cancer specific survival (CSS), and recurrence-free survival (RFS) were calculated by standard meta-analysis techniques. The results suggested that DM was associated with poor OS (HR 1.56, 95% CI, 1.35-1.81, P < 0.001), poor CSS (HR 2.03, 95% CI, 1.37-3.01, P < 0.001), and poor RFS (HR 1.73, 95% CI, 1.25-2.39, P = 0.012). In addition, for patients with localized RCC, patients with clear cell RCC, or patients receiving nephrectomy, DM was associated with both poor OS and CSS by subgroup analyses. Our study revealed that there was a significant negative impact of DM on OS, CSS, and RFS in RCC patients. Therefore, more attention should be paid to RCC patients with preexisting DM because of their poor prognosis. PMID- 26131820 TI - Differential Clinical Impact of Ascites in Cirrhosis and Idiopathic Portal Hypertension. AB - Cirrhosis and idiopathic portal hypertension (IPH) are 2 major diseases showing portal hypertension. However, characteristics and outcomes of IPH with ascites have not yet been determined. The aim of the study was to examine the influence of ascites on the long-term clinical course of IPH.This observational study compared the long-term clinical findings including portal hemodynamics demonstrated by Doppler ultrasonography between 166 cirrhosis (87 males and 79 females; mean age +/- standard deviation, 62.5 +/- 11.8 years; age range, 20-89 years) and 14 IPH patients (3 males and 11 females; mean age +/- standard deviation, 64.2 +/- 6.6 years; age range, 51-78 years). Both groups comprised of consecutive patients from November 2007 through February 2013 and were studied retrospectively. The median observation period was 33.4 months for ascites and 34.5 months for survival.Ascites was detected in 60/166 (36.1%) and 116/166 (69.9%) cirrhosis patients and in 7/14 (50%) and 9/14 (64.3%) IPH patients, at baseline and at the end of the observation period, respectively. The cumulative incidence of ascites was 12.3% at 1 year, 35.9% at 3 years, and 59.9% at 5 years in cirrhosis, and 25% at 3 years, and 50% at 5 years in IPH (P = 0.36). Deterioration of ascites in patients showing mild ascites at baseline was found in 32.4% of cirrhosis patients and 42.9% of IPH patients (P = 0.41). Serum creatinine (mg/dl) at baseline was significantly higher in IPH patients who developed ascites (n = 2, 0.74 +/- 0.14) than in those who did not (n = 5, 0.526 +/- 0.06, P = 0.029). The overall survival rate appeared to favor IPH (100% at 1 year, 92.9% at 3 and 5 years; P = 0.2) more than cirrhosis (87.7% at 1 year, 75.2% at 3 years, and 63.6% at 5 years), but did not reach statistical significance. However, in patients with ascites at baseline, the survival rate was significantly better in IPH (100% at 1, 3, and 5 years, P = 0.04) than in cirrhosis (69.1% at 1 year, 43% at 3 years, 34.4% at 5 years).The presence of ascites at baseline correlated with worse survival rates in patients with cirrhosis as compared to those with IPH as the underlying etiology. PMID- 26131821 TI - Surgical Versus Conservative Treatments for Displaced Midshaft Clavicular Fractures: A Systematic Review of Overlapping Meta-Analyses. AB - Multiple meta-analyses have been performed to compare surgical and conservative interventions for treating displaced midshaft clavicular fractures. But conclusions are discordant.The purposes of current study were (1) to conduct a systematic review of meta-analyses comparing surgical and conservative interventions for the treatment of displaced midshaft clavicular fractures, (2) to help decision makers interpret and choose among discordant meta-analyses, and (3) to provide treatment recommendations through the best available evidence.We searched the Cochrane library, PubMed, and EMBASE databases to identify meta analyses comparing surgical and conservative treatments for the displaced midshaft clavicular fractures. Two investigators independently scanned titles and abstracts to exclude irrelevant articles and identify meta-analyses that met the eligibility criteria. The methodological quality of the meta-analysis was independently assessed by the two investigators using the Oxford Centre for Evidence-based Medicine Levels of Evidence and the Assessment of Multiple Systematic Reviews (AMSTAR) tool. The Jadad decision algorithm was applied to determine which of the included studies provided the best available evidence.Six meta-analyses met the eligibility criteria in this systematic review. AMSTAR scores ranged from 5 to 10. The Jadad decision-making tool suggests that the highest quality review should be selected based on the publication characteristics of the primary trials, the methodology of the primary trials, the language restrictions, and whether analysis of data on individual patients was included in the study. As a result, we selected a high-quality Cochrane review.This systematic review of overlapping meta-analyses comparing surgical and conservative treatments suggests that surgical treatment provides a lower rate of overall treatment failure and a better functional outcome, but is associated with more implant-related complications. Hence, treatment should be individualized, with careful consideration of the advantages and disadvantages of each treatment method and of patient preferences. PMID- 26131822 TI - Computed Tomography Angiography of Carotid Arteries and Vertebrobasilar System: A Simulation Study for Radiation Dose Reduction. AB - Computed tomography angiography (CTA) of carotid arteries and vertebrobasilar system is a standardized procedure with excellent image quality, but radiation exposure remains a matter of concern. The aim of this study is to examine to what extent radiation dose can be lowered in relation to a standard protocol by simulating examinations with lower tube currents applying a dedicated software.Lower tube current was simulated by a dedicated noise insertion and reconstruction software (ReconCT). In a phantom study, true scans were performed with different dose protocols and compared to the results of simulated dose reductions of the same degree, respectively. In a patient study, 30 CTAs of supra aortic vessels were reconstructed at a level of 100%, 75%, 50%, and 25% of the initial dose. Objective and subjective image analyses were performed.No significant noise differences between true scans and simulated scans of mimicked contrasted vessels were found. In the patient study, the quality scores of the 4 dose groups differed statistically significant; this difference vanished for the comparison of the 100% and 75% datasets after dichotomization into the categories of diagnostic and nondiagnostic image quality (P = .50).This study suggests an easy-to-implement method of simulating CTAs of carotid arteries and vertebrobasilar system with lower tube current for dose reduction by artificially adding noise to the original raw data. Lowering the radiation dose in a moderate extent to 75% of the original dose levels does not significantly alter the diagnostic image quality. PMID- 26131823 TI - Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy. AB - Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy.Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-beta2 glycoprotein 1 antibody (abeta2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test.Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), abeta2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology.The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment. PMID- 26131824 TI - Systematic Review and Meta-Analysis of Carotid Artery Stenting Versus Endarterectomy for Carotid Stenosis: A Chronological and Worldwide Study. AB - There are disparities among the results of meta-analyses under different circumstances of carotid artery stenting (CAS) versus endarterectomy (CEA) for carotid stenosis. This study aimed to assess the efficacies of CAS and CEA for carotid stenosis at 5-year intervals and worldwide.Comparative studies simultaneously reporting CAS and CEA for carotid stenosis with at least 10 patients in each group were identified by searching PubMed and Embase in accordance with preferred reporting items for systematic reviews and meta analyses guidelines, and by reviewing the reference lists of retrieved articles.The studies were stratified into different subgroups according to the publication year, location in which the study was mainly performed, and randomized and nonrandomized study designs.Thirty-five comparative studies encompassing 27,525 patients were identified. The risk ratios (RRs) of stroke/death when CAS was compared with CEA within 30 d of treatment were 1.51 (95% CI 1.32-1.74, P < 0.001) for overall, 1.50 (95% CI 1.14-1.98, P = 0.004) from 2011 to 2015, 1.61 (95% CI 1.35-1.91, P < 0.001) from 2006 to 2010, 1.59 (95% CI 1.27-1.99, P < 0.001) in North America, 1.50 (95% CI 1.24-1.81, P < 0.001) in Europe, 1.63 (95% CI 1.31-2.02, P < 0.001) for randomized, and 1.44 (95% CI 1.20-1.73, P < 0.001) for nonrandomized comparative studies. CEA decreased the risks of transient ischemic attack at 30 d (RR: 2.07, 95% CI 1.50 2.85, P < 0.001) and restenosis at 1-year (RR: 1.97, 95% CI 1.28-3.05, P = 0.002). Data from follow-up showed that the RRs of stroke/death were 0.74 (95% CI 0.55-0.99, P = 0.04) at 1 year, 1.24 (95% CI 1.04-1.46, P = 0.01) at 4 year, and 2.27 (95% CI 1.39-3.71, P = 0.001) at 10 year. This systematic review, compared with those of other meta-analyses, included all available comparative studies and analyzed them at 5-year intervals, in different continents, and under different study designs. Current evidence suggests that the efficacy of CEA is superior to CAS for freedom from stroke/death within 30 d, especially from 2006 to 2015, in North America and Europe. Meanwhile, the superiority was also observed for restenosis at 1-year, transient ischemic attack within 30 d, and stroke/death at 4- and 10-year follow-ups. PMID- 26131825 TI - Percutaneous Aortic Balloon Valvuloplasty and Intracardiac Adrenaline in Electromechanical Dissociation as Bridge to Transcatheter Aortic Valve Implantation. AB - This report describes an emergent balloon aortic valvuloplasty (BAV) procedure performed under cardiopulmonary resuscitation in a 79-year-old man with severe symptomatic aortic stenosis (mean gradient 78 mm Hg, valve area 0.71 cm, and left ventricular ejection fraction 40%) awaiting surgery and who was admitted for heart failure rapidly evolving to cardiogenic shock and multiorgan failure. Decision was made to perform emergent BAV. After crossing the valve with a 6 French catheter, the patient developed an electromechanical dissociation confirmed at transesophageal echocardiography and cardiac arrest. Manual chest compressions were initiated along with the application of high doses of intravenous adrenaline, and BAV was performed under ongoing resuscitation. Despite BAV, transoesophageal echocardiography demonstrated no cardiac activity. At this point, it was decided to advance a pigtail catheter over the wire already in place in the left ventricle and to inject intracardiac adrenaline (1 mg, followed by 5 mg). Left ventricular contraction progressively resumed and, in the absence of aortic regurgitation, an intraaortic balloon pump was inserted. The patient could be weaned from intraaortic balloon pump and vasopressors on day 1, extubated on day 6, and recovered from multiorgan failure. In the absence of neurologic deficits, he underwent uneventful transcatheter aortic valve implantation on day 12 and was discharged to a cardiac rehabilitation program on day 30. At 3-month follow-up, he reported dyspnea NYHA class II as the only symptom.This case shows that severe aortic stenosis leading to electromechanical dissociation may be treated by emergent BAV and intracardiac administration of high-dose adrenaline. Intracardiac adrenaline may be considered in case of refractory electromechanical dissociation occurring in the cardiac catheterization laboratory. PMID- 26131826 TI - Long-Term Follow-Up of the Therapeutic Outcomes for Papillary Thyroid Carcinoma With Distant Metastasis. AB - Papillary thyroid carcinoma (PTC) patients with distant metastasis (DM) have variable clinical courses and therapeutic outcomes. Survival time after diagnosis of DM may be several months to years. Long-term follow-up is necessary to determine prognostic factors for survival in PTC with DM. The purpose of this study was to investigate the clinical features and therapeutic outcomes of PTC with DM after 10 years of follow-up. The study population consisted of 70 patients who underwent initial thyroidectomy before 2004 and had DM beyond the locoregional neck area. Of these 70 patients, 40 patients were diagnosed with DM before or within 9 months after initial thyroidectomy in first radioactive iodide (I) whole-body scintigraphy (group A), and 30 patients were diagnosed with DM during the follow-up period (group B). Patients with DM underwent 3.7 to 7.4 GBq I therapy every 6 to 12 months. After a mean follow-up period of 10.1 +/- 0.9 years, the disease-specific mortality and remission rates were 70.0% (49/70) and 10% (7/70), respectively. The survival rates for patients in groups A and B were 72.5% and 96.7% at 1 year, 47.5% and 90.0% at 5 years, 40.0% and 70.0% at 10 years, 36.4% and 41.1% at 15 years, and 35.0% and 8.0% at 20 years, respectively. The percentage of male and older patients and patients with larger tumor size was higher in the mortality group than in the survival group, whereas the percentage of patients with I avid metastatic lesions (first DM) was lower in the mortality group. The percentage of patients with secondary primary cancers was higher in group B than in group A. In the multiple regression analysis, age and male gender were independently associated with disease-specific mortality. In conclusion, after a mean follow-up of 10.1 years, the disease-specific mortality rate for PTC with DM was 70.0%. Older patients and male PTC patients with DM need more aggressive treatment. The timing of DM diagnosis did not influence disease specific mortality. PMID- 26131827 TI - Alcohol Drinking Obliterates the Inverse Association Between Serum Retinol and Risk of Head and Neck Cancer. AB - This analysis evaluated the association between serum retinol levels and risk of head and neck cancer (HNC) and whether the association is modulated by the use of alcohol, betel quid, or cigarette. In addition, we also examined the association between HNC risk and 2 single nucleotide polymorphisms, TTR rs1667255 and RBP4 rs10882272, that have been associated with serum retinol levels. Unconditional logistic regression was performed to evaluate the association between serum retinol levels and HNC risk among 160 HNC cases and 198 controls. The associations between TTR rs1667255 and RBP4 rs10882272 and serum retinol levels or HNC risk were evaluated by linear regression and unconditional logistic regression, respectively, for 418 HNC cases and 497 controls. The results showed that HNC cases had a lower mean serum retinol level compared with controls (845.3 MUg/L vs 914.8 MUg/L, P = 0.03). An inverse association between serum retinol levels and HNC risk occurred among never/occasional alcohol drinkers but not among regular drinkers. TTR rs1667255 was associated with serum retinol levels; however, neither TTR rs1667255 nor RBP4 rs10882272 was associated with HNC risk. In summary, this study showed an inverse association between serum retinol levels and HNC risk, specifically among never/occasional alcohol drinkers. More studies are needed to establish the underlying biologic mechanisms for the inverse association between serum retinol levels and HNC risk and the modulation of this relationship by alcohol drinking. PMID- 26131828 TI - Adjuvant therapy use among Appalachian breast cancer survivors. AB - There is a paucity of literature systemically examining the effects of access to cancer care resources on adjuvant endocrine therapy (AET) use behaviors, especially in underserved regions such as the Appalachian region in the United States, where gaps in healthcare access are well documented. The objectives of this study were to explore AET adherence and persistence in Appalachia, delineate the effects of access to care cancer on adherence/persistence, and evaluate the influences of adherence and persistence on overall survival.A retrospective cohort study from 2006 to 2008 was conducted among female breast cancer survivors living in the Appalachian counties of 4 states (PA, OH, KY, and NC). We linked cancer registries to Medicare claims data and included patients with invasive, nonmetastatic, hormone-receptor-positive breast cancer who received guideline recommended AET. Medication adherence was defined as corresponding to a Medication Possession Ratio (MPR) >=0.8 and logistic regression was utilized to assess predictors of adherence. Medication nonpersistence was defined as the discontinuation of drugs after exceeding a 60-day medication gap, and multivariate adjusted estimates of nonpersistence were obtained using the Cox proportional hazards (PH) model.About 31% of the total 428 patients were not adherent to AET, and 30% were not persistent over an average follow-up period of 421 days. Tamoxifen, relative to aromatase inhibitors, was associated with higher odds of adherence (odds ratio = 2.82, P < 0.001) and a lower risk of nonpersistence (hazard ratio = 0.40, P < 0.001). Drug-related side effects like pain may be an important factor leading to nonadherence and early discontinuation. In addition, aromatase inhibitor (AI) adherence and persistence were significantly influenced by out-of-pocket drug costs, dual eligibility status, and coverage gaps. Nonadherence to and nonpersistence with AET were associated with higher risks of all-cause mortality.Our findings of suboptimal AET adherence/persistence in Appalachia as well as positive associations between AET adherence/persistence and overall survival outcomes further underscore the importance of ensuring appropriate AET use in this population to reduce breast cancer mortality disparities. Our findings also suggest that intervention strategies focusing on individualized treatment and medication-related factors may improve adjuvant treatment use. PMID- 26131829 TI - Surgical Resection of a Progressive Giant Arteriovenous Malformation After 13 year Follow-Up. AB - Giant arteriovenous malformation (AVM) is a complex and relatively rare congenital lesion with high morbidity and mortality. Its optimal treatment, however, remains controversial. Normal perfusion pressure breakthrough (NPPB) is a potentially devastating complication following surgical resection. Generally, strict blood pressure control is particularly recommended for preventing this phenomenon. Here we present a case of a 21-year-old patient with a progressive giant AVM who developed frequent seizures and subsequently underwent microsurgical total resection after 13-year follow-up, complicated by NPPB. Hypertensive hypervolemic treatment rather than strict blood pressure control was administrated postoperatively; however thalamic infarction occurred. During the 1 year of follow-up, the patient remained seizure-free with only mild right-sided hemiparesis.This case highlights that, in view of potential growth of the lesion, early intervention is necessary when possible. Microsurgical resection is challenging but remains to be an effective option for eliminating such giant AVM, and it is vital to keep risks associated with surgery in mind, such as NPPB. Moreover, whether blood pressure control is needed or not should be individualized. PMID- 26131830 TI - Medical Comics as Tools to Aid in Obtaining Informed Consent for Stroke Care. AB - Informed consent has now become common in medical practice. However, a gap still exists between doctors and patients in the understanding of clinical conditions. We designed medical comics about "subarachnoid hemorrhage" and "intracerebral hemorrhage" to help doctors obtain informed consent intuitively, quickly, and comprehensively.Between September 2010 and September 2012, we carried out a questionnaire survey about medical comics with the families of patients who had suffered an intracerebral or subarachnoid hemorrhage. The questionnaire consisted of 6 questions inquiring about their mental condition, reading time, usefulness of the comics in understanding brain function and anatomy, pathogenesis, doctor's explanation, and applicability of these comics.The results showed that 93.8% responders would prefer or strongly prefer the use of comics in other medical situations. When considering the level of understanding of brain function and anatomy, pathology of disease, and doctor's explanation, 81.3%, 75.0%, and 68.8% of responders, respectively, rated these comics as very useful or useful.We think that the visual and narrative illustrations in medical comics would be more helpful for patients than a lengthy explanation by a doctor. Most of the responders hoped that medical comics would be applied to other medical cases. Thus, medical comics could work as a new communication tool between doctors and patients. PMID- 26131831 TI - Incidence of Second Primary Malignancies Following Colorectal Cancer: A Distinct Pattern of Occurrence Between Colon and Rectal Cancers and Association of Co Morbidity with Second Primary Malignancies in a Population-Based Cohort of 98,876 Patients in Taiwan. AB - The purpose of this study is to determine the features of second primary malignancies (SPMs) among patients with prior colorectal cancer (CRC) using a nationwide population-based dataset.Patients with CRC newly diagnosed between 1996 and 2011, and >1 year of follow-up were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of SPMs in patients with CRC were calculated.During the 16-year study period, 4259 SPMs developed among 98,876 CRC patients. The median duration of follow-up was 4.03 years. The SIR for all SPMs was 1.13 (95% confidence interval = 1.10-1.17). Compared with the general population, a higher incidence of thyroid, prostate, ovarian, and hematologic malignancies developed among patients with colon cancer, whereas the risk for bone and soft tissue cancers increased among patients with rectal cancer. The risk for breast, bladder, kidney, lung, and uterine cancers was significantly higher in patients with colon and rectal cancers than the general population. The risk for liver and biliary tract cancers declined in patients with rectal cancer. Based on multivariate analysis among patients with CRC, age >=70 years, men, chronic obstructive pulmonary disease (COPD), cirrhosis, and dyslipidemia were independent predictors of an SPM.In conclusion, patients with CRC were at increased risk for a second cancer. The pattern of SPMs was distinct between patients with colon and rectal cancer. Age, men, COPD, cirrhosis, and dyslipidemia were independent risk factors for SPMs. Surveillance and education should be provided for survivors with respect to risk for SPMs. PMID- 26131832 TI - Myocarditis in Patients With Antisynthetase Syndrome: Prevalence, Presentation, and Outcomes. AB - Antisynthetase syndrome (aSS) corresponds to an overlapping inflammatory myopathy identified by various myositis-specific autoantibodies (directed against tRNA synthetases). Myocardial involvement in this condition is poorly described.From a registry of 352 aSS patients, 12 cases of myocarditis were retrospectively identified on the basis of an unexplained increase in troponin T/I levels associated with either suggestive cardiac magnetic resonance imaging (MRI) findings, nonsignificant coronary artery abnormalities or positive endomyocardial biopsy.The prevalence of myocarditis in aSS is 3.4% and was not linked to any autoantibody specificity: anti-Jo1 (n = 8), anti-PL7 (n = 3), and anti-PL12 (n = 1). Myocarditis was a part of the first aSS manifestations in 42% of the cases and was asymptomatic (n = 2) or revealed by an acute (n = 4) or a subacute (n = 6) cardiac failure. It should be noted that myocarditis was always associated with an active myositis. When performed (n = 11), cardiac MRI revealed a late hypersignal in the T1-images in 73% of the cases (n = 8). Half of the patients required intensive care. Ten patients (83%) received dedicated cardiotropic drugs. Steroids and at least 1 immunosuppressive drug were given in all cases. After a median follow-up of 11 months (range 0-84) 9 (75%) patients recovered whereas 3 (25%) developed a chronic cardiac insufficiency. No patient died.The prevalence of myocarditis in aSS is similar to that of other inflammatory myopathies. Although the prognosis is relatively good, myocarditis is a severe condition and should be carefully considered as a possible manifestation in active aSS patients. PMID- 26131833 TI - The Combined Effect of Ear Lobe Crease and Conventional Risk Factor in the Diagnosis of Angiographically Diagnosed Coronary Artery Disease and the Short Term Prognosis in Patients Who Underwent Coronary Stents. AB - The role of diagonal ear lobe crease (DELC) in coronary artery disease (CAD) diagnosis and prognosis remains controversial. In this study, we aimed to assess the combined effect of DELC with other conventional risk factors in the diagnosis and prognosis of CAD in Chinese patients who underwent angiography and coronary stent implantation.The study consisted of 956 consecutive patients who underwent angiography. The DELC was identified as no DELC, unilateral, and bilateral DELC. The conventional risk factors for CAD were recorded.Our dada showed that the overall presence of DELC is associated with CAD risk. Stratification analyses revealed that the diagnostic value of DELC was mostly significant in those with >4 risk factors. Also in patients with >4 risk factors, the presence of bilateral DELC remains to be associated with higher hs-CRP level, higher severity of CAD, and higher possibility of developing major adverse cardiac events after successful percutaneous coronary intervention (PCI).Our study confirmed the relation of DELC with CAD in Chinese patients; more importantly, our data suggest the combination of DELC and CAD risk factors will help to predict the incidence of CAD and may predict the prognosis after successfully PCI. PMID- 26131834 TI - Epidemiological and Clinicopathological Trends of Breast Cancer in Chinese Patients During 1993 to 2013: A Retrospective Study. AB - This study aimed to summarize the epidemiological and pathological trends of breast cancer in Chinese women.The clinical data of 4968 breast cancer patients treated at the Chinese PLA General Hospital from 1993 to 2013 were retrospectively reviewed.The mean +/- standard deviation (SD) age was 47.4 +/- 11.3 years before the year 2001, 49.2 +/- 11.2 years during 2001 to 2010, and 50.6 +/- 11.4 years after the year 2010, respectively (P < 0.001). The ratio of premenopausal women to postmenopausal women was 1.6 and no significant changes were found during the period (P = 0.121). The proportion of patients with Scarff Bloom Richardson III breast cancer showed significant increase along with time (P = 0.015). The breast cancer was accounting for 31.7% at stage I and DCIS/LCIS and tend to be diagnosed with early stage around time (P < 0.001). The proportion of DCIS/LCIS and stage I increased with time during the 20 years from 14.6% to 33.2%, whereas the proportion of stage III to IV decreased.The proportion of Luminal A-like subtype gradually reduced and Luminal B-like (HER2-negative) increased and developed to the predominant type. Older age and earlier stage at diagnosis, as well as the alternation of predominant molecular subtypes, have become the developed trends of breast cancer. PMID- 26131835 TI - Emergency Presentations With Nonspecific Complaints-the Burden of Morbidity and the Spectrum of Underlying Disease: Nonspecific Complaints and Underlying Disease. AB - The prevalence of diagnoses, morbidity, and mortality of patients with nonspecific complaints (NSC) presenting to the emergency department (ED) is unknown.To determine the prevalence of diagnoses, acute morbidity, and mortality of patients with NSC.Prospective observational study with a 30-day follow-up. Patients presenting to 2 EDs were enrolled by a study team and diagnosed according to the World Health Organization ICD-10 System.Of 217,699 presentations to the ED from May 2007 through to February 2011, a total of 1300 patients were enrolled. After exclusion of 90 patients who fulfilled exclusion criteria, 1210 patients were analyzed. No patient was lost to follow-up. In patients with NSC, the underlying diseases were spread throughout 18 chapters of the ICD-10. A total of 58.7% of the patients were diagnosed with acute morbidity. Thirty-day mortality was 6.4% overall. Patients with acute morbidity and suffering from heart failure and pneumonia had mortalities >15%; patients lacking acute morbidity, but suffering from functional impairment or depression/anxiety had mortalities of 0%. Although the history did not allow any prediction, age and sex were predictive of morbidity and mortality.The differential diagnoses in patients presenting with NSC is broad. Acute morbidity and mortality were high in the presented cohort, the predictors of morbidity and mortality being age and sex rather than the nature of the complaints. Urgently needed management strategies could be based on these results.ClinicalTrials.gov (#NCT00920491). PMID- 26131836 TI - Lymphoma-Like Syndrome: 4 Case Reports About Atypical Presentation of Primary Cytomegalovirus Infection in Immunocompetent Children. AB - In immunocompetent persons, primary cytomegalovirus (CMV) infection is self limited infection. Lymphoma-like syndromes have been sometimes described in adults but have not been described for children.Lymphoma-like syndromes (protracted fever, alteration of the general status, and clinical lymphoproliferative syndrome) were retrospectively recorded in children attending our hospital from 1999 to 2008 for primary CMV infection. Patients with immunodeficiency, coinfection (Epstein-Barr virus, toxoplasmosis, or mycobacterial), or biological criteria of mononucleosis-like syndrome were excluded.We report 4 cases of lymphoma-like syndrome. The median duration of fever was 21.5 days (range 15-27). Tonsillitis and hepatitis are most of the time missing. A probable malignant diagnosis was raised in 3 cases. Clinical outcome was protracted (15-35 days) but favorable.To our knowledge, our study is the first pediatric case series of lymphoma-like syndrome. This clinical presentation is a source of delayed diagnosis due to diagnosis pitfall. PMID- 26131837 TI - Impact of a New Medical Record System for Emergency Departments Designed to Accelerate Clinical Documentation: A Crossover Study. AB - Recording information in emergency departments (EDs) constitutes a major obstacle to efficient treatment. A new electronic medical records (EMR) system focusing on clinical documentation was developed to accelerate patient flow. The aim of this study was to examine the impact of a new EMR system on ED length of stay and physician satisfaction.We integrated a new EMR system at a hospital already using a standard system. A crossover design was adopted whereby residents were randomized into 2 groups. Group A used the existing EMR system first, followed by the newly developed system, for 2 weeks each. Group B followed the opposite sequence. The time required to provide overall medical care, length of stay in ED, and degree of physician satisfaction were compared between the 2 EMR systems.The study involved 6 residents and 526 patients (277 assessed using the standard system and 249 assessed with the new system). Mean time for clinical documentation decreased from 133.7 +/- 5.1 minutes to 107.5 +/- 5.4 minutes with the new EMR system (P < 0.001). The time for overall medical care was significantly reduced in all patient groups except triage level 5 (nonurgent). The new EMR system significantly reduced the length of stay in ED for triage level 2 (emergency) patients (145.4 +/- 13.6 minutes vs 184.3 +/- 13.6 minutes for standard system; P = 0.047). As for the degree of physician satisfaction, there was a high degree of satisfaction in terms of the physical findings support system and the ability to capture images and enter negative findings.The new EMR system shortened the time for overall medical care and was associated with a high degree of resident satisfaction. PMID- 26131838 TI - A Prospective Follow-Up of Adipocytokines in Cohort Patients With Gout: Association With Metabolic Syndrome But Not With Clinical Inflammatory Findings: Strobe-Compliant Article. AB - The aim of this study was to determine the levels of leptin (Lep) and adiponectin (AdipoQ) in patients with gout and its relationship with joint inflammatory data and/or with metabolic syndrome (MetS) variables, during 1 year follow-up.Forty one patients (40 males) with gout diagnosis, attending for the first time to a rheumatology department, were included. Evaluations were performed baseline, at 6 and 12 months. Variables included the following: demographic, clinical and laboratory data related to gout and associated diseases. Lep and AdipoQ determinations by the ELISA method were performed in frozen serum from each visit. The pharmacological and no-pharmacological treatment for gout and associated diseases was individualized for each patient according to published guidelines. Statistical analysis included Mann-Whitney U test, Fisher test, x, ANOVA, Cochran Q, Pearson and Spearman correlation tests, as well as linear regression.In the baseline evaluation, 29.2% had MetS (hypertriglyceridemia 66%, hypertension 44% and obesity 37%); patients with MetS had higher C reactive protein (CRP) levels [34.1 +/- 28.6 vs. 12.2 +/- 11.2 mg/dL, P = 0.033]. Although not significant, also had higher Lep and lower AdipoQ levels (3.2 +/- 3.0 vs. 1.9 +/- 1.2 ng/mL, P = 0.142 and 40.5 +/- 26.8 vs. 38.0 +/- 24.9 ng/mL, P = 0.877, respectively). During follow-up, our patients had significant improvement in serum uric acid (sUA) levels and variables evaluating pain and joint swelling (P <= 0.05). Metabolic abnormalities tended to persist or even worsen during the monitoring period: significant increase in total cholesterol (P = 0.004), tendency to higher triglycerides (P = 0.883) and slight improvement in glycaemia (P = 0.052). Lep values increased significantly during follow-up (P = 0.001) while AdipoQ levels diminished slightly (P = 0.317). Neither Lep nor AdipoQ values showed important correlation (r > 0.5) with metabolic variables or joint swelling.This study suggests that in patients with gout, concentrations of Lep and AdipoQ are more in line with the metabolic state than with clinical disease activity. PMID- 26131839 TI - Characteristics of Internal Medicine Physicians Disciplined by Professional Colleges in Canada. AB - Physician misconduct is of serious concern to patient safety and quality of care. Currently, there are limited data on disciplinary proceedings involving internal medicine (IM) physicians.The aim of this study was to investigate the number and nature of disciplinary cases among IM physicians compared with those of other disciplined physicians.Our retrospective study reviewed information from all provincial Colleges of Physicians and Surgeons (CPS) and compiled a database of all disciplined physicians from 2000 to 2013 in Canada. Disciplinary rate differences (RDs) were calculated for IM physicians and compared with other physicians.From 2000 to 2013, overall disciplinary rates were low (9.6 cases per 10,000 physician years). There were 899 disciplinary cases, 49 of which involved 45 different IM physicians. IM physicians comprised 10.8% of all disciplined physicians and were disciplined at a lower rate than non-IM physicians, incurring 5.18 fewer cases per 10,000 physician years than other physicians (95% confidence interval [CI] 3.62-6.73; P < 0.001). They were significantly less likely to be disciplined for: unprofessional conduct (RD 1.16; CI 0.45-1.87; P = 0.001); unlicensed activity (RD 0.78; CI 0.37-1.19; P < 0.001); standard of care issues (RD 1.37; CI 0.49-2.26; P = 0.002); sexual misconduct (RD 1.65; CI 0.90-2.40; P < 0.001); miscellaneous (RD 0.80; CI 0.11-1.50; P = 0.020); mental illness (RD 0.06; CI 0.01-0.12; P = 0.025); inappropriate prescribing (RD 0.74; CI 0.15-1.33; P = 0.010); and criminal conviction (RD 0.33; CI 0.00-0.65; P = 0.048). No significant differences were found with respect to unclear violations, fraudulent behavior/prevarication, or offenses involving drugs/alcohol (all RDs less than 0.32). IM physicians were also less likely to incur the following penalties: voluntary license surrender (RD 0.53; CI 0.37-0.69; P < 0.001); suspension (RD 2.39; CI 1.26-3.51; P < 0.001); retraining/assessment (RD 1.58; CI 0.77-2.39; P < 0.001); restriction (RD 1.60; CI 0.74-2.46; P < 0.001); other (RD 0.52; CI 0.07 0.97; P = 0.030); formal reprimand (RD 2.78; CI 1.77-3.79; P < 0.001); or fine (RD 3.28; CI 1.89-4.67; P < 0.001). No significant differences were found with respect to revocation or mandated counseling/rehabilitation (all RDs less than 0.46).Generally, disciplinary rates among physicians were low. Compared with other physicians, IM physicians have significantly lower disciplinary rates overall and are less likely to incur the majority of disciplinary offenses and penalties. PMID- 26131840 TI - Pancreatic Adenocarcinoma Treated With Irreversible Electroporation Case Report: First Experience and Outcome. AB - Irreversible electroporation (IRE) is a new nonthermal tumor ablation modality that induces apoptosis in the treated tissue without affecting collagen. Its use is particularly indicated for tumors involving major structures, such as encompassed or infiltrated vessels and/or ducts, which need to be preserved and hinder or preclude surgical resection. We report a 66-year-old male patient with locally advanced pancreatic adenocarcinoma, treated with IRE.Two cycles of neoadjuvant chemotherapy with nab-paclitaxel and gemcitabine were administered. After these 2 cycles, IRE ablation was performed with a percutaneous transgastric access under general anesthesia. Later, 4 additional chemotherapy cycles were administrated. At 48 hours of electroporation, blood tests were normal. On day 5, a computed tomography (CT) scan showed portal vein and celiac artery were normal in appearance. Three months later, a positron emission tomography (PET) scan showed disappearance of abnormal uptake in the pancreas and other sites. A 12 month follow-up the patient is disease free.IRE opens a new way to treat tumors with involvement or proximity of neighboring structures. This procedure is more costly than other techniques and is not free of complications. The percutaneous transgastric access is feasible and without serious complications. In our case, complications were resolved and the patient presented a good short/medium-term outcome. PMID- 26131841 TI - eNOS Genetic Polymorphisms and Cancer Risk: A Meta-Analysis and a Case-Control Study of Breast Cancer. AB - The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case-control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility.Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and 786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case-control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV.In conclusion, our meta-analysis and case-control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer. PMID- 26131842 TI - Sleep Disturbance and Altered Expression of Circadian Clock Genes in Patients With Sudden Sensorineural Hearing Loss. AB - The cause of sudden sensorineural hearing loss (SSNHL) remains unclear and therefore it is often considered as idiopathic. Sleep disturbance has been linked to SSNHL and circadian rhythm disruption, but the link between circadian rhythm disruption and SSNHL has never been investigated.In this study, we surveyed the sleep quality of 38 patients with SSNHL using a simple insomnia sleep questionnaire. The expression of circadian clock genes in peripheral blood (PB) leukocytes from 38 patients with SSNHL and 71 healthy subjects was accessed using real-time quantitative reverse transcriptase-polymerase chain reaction and validated using immunocytochemical staining.We found that 61.8% of patients with SSNHL suffered from insomnia before the insult of hearing loss. Besides, significantly decreased expression of PER1, CRY1, CRY2, CLOCK, BMAL1, and CKlepsilon was found in PB leukocytes of patients with SSNHL when compared with healthy subjects. SSNHL patients with vertigo had significantly lower expression of CRY1 and CKlepsilon than patients without vertigo symptoms. Our results imply the association of sleep disturbance and disrupted circadian rhythm in SSNHL. PMID- 26131843 TI - Behavior of Small, Asymptomatic, Nonfunctioning Pancreatic Neuroendocrine Tumors (NF-PNETs). AB - Small nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) usually exhibit minimal or no growth over many years. However, there is a controversy regarding the optimal management of incidentally discovered, small NF-PNETs. This study aimed to gain insights into tumor behavior and potential strategies for clinical management.We retrospectively reviewed a total of 202 patients with a suspected PNET (size 2 cm or smaller) at Samsung Medical Center from January 1, 1995 to April 30, 2012. Among these patients, 72 patients were excluded and 145 patients were enrolled in our study. Patients were included if the size of the tumor was <=2 cm without familial syndrome, radiographic evidence of local invasion or metastases.Among the 145 patients, 76 patients (52.4%) had pathologically confirmed PNETs. Eleven (14.5%) and 3 (3.9%) of these 76 patients were diagnosed with NET G2 and G3, respectively. PNETs measuring 1.5 cm or more in size had a higher probability of being classified as NET G2 or G3 compared with PNETs measuring <1.5 cm (P = 0.03). Older age (>=55 years) and a meaningful tumor growth (>=20% or >=5 mm) were significantly associated with NET G2 or G3 (P < 0.05).Older age (>=55 years), larger tumor size (>=1.5 cm), and a meaningful tumor growth (>=20% or >=5 mm) were associated with NET G2 or G3. Intensive follow-up could be an acceptable approach in small (especially <1.5 cm), asymptomatic, NF-PNETs. PMID- 26131844 TI - Bone metastases in lung cancer. Potential novel approaches to therapy. AB - The skeleton is a common site of metastases in lung cancer, an event associated with significant morbidities and poor outcomes. Current antiresorptive therapies provide limited benefit, and novel strategies of prevention and treatment are urgently needed. This review summarizes the latest advances and new perspectives on emerging experimental and clinical approaches to block this deleterious process. Progress propelled by preclinical models has led to a deeper understanding on the complex interplay of tumor cells in the osseous milieu, unveiling potential new targets for drug development. Improvements in early diagnosis through the use of sophisticated imaging techniques with bone serum biomarkers are also discussed in the context of identifying patients at risk and monitoring disease progression during the course of treatment. PMID- 26131845 TI - Correction: Multicolor Whole-Cell Bacterial Sensing Using a Synchronous Fluorescence Spectroscopy-Based Approach. AB - [This corrects the article DOI: 10.1371/journal.pone.0122848.]. PMID- 26131846 TI - Impact of End-Tethered Polyhedral Nanoparticles on the Mobility of Poly(dimethylsiloxane). AB - A series of dumbbell-shaped nanocomposite materials of poly(dimethylsiloxanes) (PDMSs) and polyhedral oligomeric silsesquioxanes (POSSs) were synthesized through hydrosilylation reactions of allyl- and vinyl-POSS and hydride-terminated PDMS. The chemical structures of the dumbbell-shaped materials, so-called POSS PDMS-POSS triblocks, were characterized by (1)H NMR and FT-IR spectroscopy. The molecular weights of the triblock polymers were determined by gel permeation chromatography (GPC). Their size was analyzed by small-angle neutron scattering (SANS) and pulsed-field gradient stimulated echo (PFG STE) NMR experiments. The impact of POSS on the molecular mobility of the PDMS middle chain was observed by using (1)H spin-spin (T2) relaxation NMR. In contrast to the PDMS melts, the triblocks showed an increase in mobility with increasing molecular weight over the range studied due to the reduced relative concentration of constraints imposed by the end-tethered nanoparticles. The triblock systems were used to compare the impact of tethered nanoparticles on the mobility of the linear component compared to the mobility of the polymer in conventional blended nanocomposites. The tethered nanoparticles were found to provide more reinforcement than physically dispersed particles especially at high molecular weights (low particle concentration). The physical blends showed an apparent percolation threshold behavior. PMID- 26131847 TI - Converting Transaldolase into Aldolase through Swapping of the Multifunctional Acid-Base Catalyst: Common and Divergent Catalytic Principles in F6P Aldolase and Transaldolase. AB - Transaldolase (TAL) and fructose-6-phosphate aldolase (FSA) both belong to the class I aldolase family and share a high degree of structural similarity and sequence identity. The molecular basis of the different reaction specificities (transferase vs aldolase) has remained enigmatic. A notable difference between the active sites is the presence of either a TAL-specific Glu (Gln in FSA) or a FSA-specific Tyr (Phe in TAL). Both residues seem to have analoguous multifunctional catalytic roles but are positioned at different faces of the substrate locale. We have engineered a TAL double variant (Glu to Gln and Phe to Tyr) with an active site resembling that of FSA. This variant indeed exhibits aldolase activity as its main activity with a catalytic efficiency even larger than that of authentic FSA, while TAL activity is greatly impaired. Structural analysis of this variant in complex with the dihydroxyacetone Schiff base formed upon substrate cleavage identifies the introduced Tyr (genuine in FSA) to catalyze protonation of the central carbanion-enamine intermediate as a key determinant of the aldolase reaction. Our studies pinpoint that the Glu in TAL and the Tyr in FSA, although located at different positions at the active site, similarly act as bona fide acid-base catalysts in numerous catalytic steps, including substrate binding, dehydration of the carbinolamine, and substrate cleavage. We propose that the different spatial positions of the multifunctional Glu in TAL and of the corresponding multifunctional Tyr in FSA relative to the substrate locale are critically controlling reaction specificity through either unfavorable (TAL) or favorable (FSA) geometry of proton transfer onto the common carbanion-enamine intermediate. The presence of both potential acid-base residues, Glu and Tyr, in the active site of TAL has deleterious effects on substrate binding and cleavage, most likely resulting from a differently organized H-bonding network. Large-scale motions of the protein associated with opening and closing of the active site that seem to bear relevance for catalysis are observed as covalent intermediates are exclusively observed in the "closed" conformation of the active site. Pre-steady-state kinetics are used to monitor catalytic processes and structural transitions and to refine the kinetic framework of TAL catalysis. PMID- 26131848 TI - Using Google Reverse Image Search to Decipher Biological Images. AB - Despite the range of tasks performed by biological image-processing software, current versions cannot find matches for the image in question among the huge range of biological images that exist in the literature and elsewhere on the Internet. Google's Reverse Image Search is designed for this, and it is a simple, yet powerful tool that can be applied to decipher the contents of biological images. For images that contain unfamiliar or unknown elements, for example, Reverse Image Search can identify similar features in published images. Here we describe general guidelines for using this freely available tool to search published images in National Center for Biotechnology Information's (NCBI's) image database. These guidelines can be applied to a variety of types of biological images, including immunohistochemistry and electron microscopy, to facilitate straightforward and rapid searches using Google's Reverse Image Search. PMID- 26131849 TI - MARCC (Matrix-Assisted Reader Chromatin Capture): An Antibody-Free Method to Enrich and Analyze Combinatorial Nucleosome Modifications. AB - Combinatorial patterns of histone modifications are key indicators of different chromatin states. Most of the current approaches rely on the usage of antibodies to analyze combinatorial histone modifications. Here we detail an antibody-free method named MARCC (Matrix-Assisted Reader Chromatin Capture) to enrich combinatorial histone modifications. The combinatorial patterns are enriched on native nucleosomes extracted from cultured mammalian cells and prepared by micrococcal nuclease digestion. Such enrichment is achieved by recombinant chromatin-interacting protein modules, or so-called reader domains, which can bind in a combinatorial modification-dependent manner. The enriched chromatin can be quantified by immunoblotting or mass spectrometry for the co-existence of histone modifications, while the associated DNA content can be analyzed by qPCR or next-generation sequencing. Altogether, MARCC provides a reproducible, efficient and customizable solution to enrich and analyze combinatorial histone modifications. PMID- 26131850 TI - Gene Silencing by RNAi in Mammalian Cells. AB - This unit provides information how to use short interfering RNA (siRNA) for sequence-specific gene silencing in mammalian cells. Several methods for siRNA generation and optimization, as well as recommendations for cell transfection and transduction, are presented. PMID- 26131851 TI - Assaying Cell Cycle Status Using Flow Cytometry. AB - In this unit, two protocols are described for analyzing cell cycle status using flow cytometry. The first is based on the simultaneous analysis of proliferation specific marker (Ki-67) and cellular DNA content, which discriminate resting/quiescent cell populations (G0 cell) and quantify cell cycle distribution (G1, S, or G2/M), respectively. The second is based on differential staining of DNA and RNA through co-staining of Hoechst 33342 and Pyronin Y, which is also useful to identify G0 cells from G1 cells. Along with these methods for analyzing cell cycle status, two additional methods for cell proliferation assays with recent updates of newly developed fluorophores, which allow multiplex analysis of cell cycle status, cell proliferation, and a gene of interest using flow cytometry, are outlined. PMID- 26131853 TI - Isolation of Nascent Transcripts with Click Chemistry. AB - Steady-state levels of cellular RNA are determined by both transcriptional rate and RNA half-life. Commonly used methods for transcriptional analysis are only capable of profiling total RNA and do not distinguish changes in synthesis and decay rates. Hence, a better understanding of the temporal dynamics of cellular response for a given condition at the transcriptional level requires techniques for the analysis of nascent transcripts. Here we describe a protocol that allows isolation of nascent transcripts with a copper-catalyzed azide-alkyne cycloaddition (CuAAC) also known as a click chemistry reaction. PMID- 26131852 TI - CRISPR-Cas9 Genome Editing in Drosophila. AB - The CRISPR-Cas9 system has transformed genome engineering of model organisms from possible to practical. CRISPR-Cas9 can be readily programmed to generate sequence specific double-strand breaks that disrupt targeted loci when repaired by error prone non-homologous end joining (NHEJ) or to catalyze precise genome modification through homology-directed repair (HDR). Here we describe a streamlined approach for rapid and highly efficient engineering of the Drosophila genome via CRISPR-Cas9-mediated HDR. In this approach, transgenic flies expressing Cas9 are injected with plasmids to express guide RNAs (gRNAs) and positively marked donor templates. We detail target-site selection; gRNA plasmid generation; donor template design and construction; and the generation, identification, and molecular confirmation of engineered lines. We also present alternative approaches and highlight key considerations for experimental design. The approach outlined here can be used to rapidly and reliably generate a variety of engineered modifications, including genomic deletions and replacements, precise sequence edits, and incorporation of protein tags. PMID- 26131854 TI - Parallel WGA and WTA for Comparative Genome and Transcriptome NGS Analysis Using Tiny Cell Numbers. AB - Genomic DNA determines how and when the transcriptome is changed by a trigger or environmental change and how cellular metabolism is influenced. Comparative genome and transcriptome analysis of the same cell sample links a defined genome with all changes in the bases, structure, or numbers of the transcriptome. However, comparative genome and transcriptome analysis using next-generation sequencing (NGS) or real-time PCR is often limited by the small amount of sample available. In mammals, the amount of DNA and RNA in a single cell is ~10 picograms, but deep analysis of the genome and transcriptome currently requires several hundred nanograms of nucleic acids for library preparation for NGS sequencing. Consequently, accurate whole-genome amplification (WGA) and whole transcriptome amplification (WTA) is required for such quantitative analysis. This unit describes how the genome and the transcriptome of a tiny number of cells can be amplified in a highly parallel and comparable process. Protocols for quality control of amplified DNA and application of amplified DNA for NGS are included. PMID- 26131855 TI - Whole-Transcriptome Amplification of Single Cells for Next-Generation Sequencing. AB - Single-cell transcriptome analysis gives insight into the heterogeneity of neighboring cells in tissues or cell cultures. It has been shown that the variability of cells is important for biological function. However, cell variability can be an indication of disease (e.g., cancer). In order to elucidate cell variability in health and disease, single-cell transcriptomes can be analyzed by new next-generation sequencing (NGS) platforms. NGS analysis currently requires a few hundred nanograms of RNA. Consequently, accurate whole transcriptome amplification is required to analyze the transcriptome of a single cell by NGS. This unit describes the entire workflow from cells to NGS, including cell quality testing, cell lysis, gDNA removal, whole-transcriptome amplification, and NGS library preparation. Recommendations for WTA quality control are given and optional protocols for using purified RNA for WTA and WTA purification are described. PMID- 26131857 TI - Extreme Levels of Suicidality Among People Who Inject Drugs in Delhi, India: A Cause for Reflection for HIV Prevention Interventions. PMID- 26131856 TI - A Simple Predictive Enhancer Syntax for Hindbrain Patterning Is Conserved in Vertebrate Genomes. AB - BACKGROUND: Determining the function of regulatory elements is fundamental for our understanding of development, disease and evolution. However, the sequence features that mediate these functions are often unclear and the prediction of tissue-specific expression patterns from sequence alone is non-trivial. Previous functional studies have demonstrated a link between PBX-HOX and MEIS/PREP binding interactions and hindbrain enhancer activity, but the defining grammar of these sites, if any exists, has remained elusive. RESULTS: Here, we identify a shared sequence signature (syntax) within a heterogeneous set of conserved vertebrate hindbrain enhancers composed of spatially co-occurring PBX-HOX and MEIS/PREP transcription factor binding motifs. We use this syntax to accurately predict hindbrain enhancers in 89% of cases (67/75 predicted elements) from a set of conserved non-coding elements (CNEs). Furthermore, mutagenesis of the sites abolishes activity or generates ectopic expression, demonstrating their requirement for segmentally restricted enhancer activity in the hindbrain. We refine and use our syntax to predict over 3,000 hindbrain enhancers across the human genome. These sequences tend to be located near developmental transcription factors and are enriched in known hindbrain activating elements, demonstrating the predictive power of this simple model. CONCLUSION: Our findings support the theory that hundreds of CNEs, and perhaps thousands of regions across the human genome, function to coordinate gene expression in the developing hindbrain. We speculate that deeply conserved sequences of this kind contributed to the co option of new genes into the hindbrain gene regulatory network during early vertebrate evolution by linking patterns of hox expression to downstream genes involved in segmentation and patterning, and evolutionarily newer instances may have continued to contribute to lineage-specific elaboration of the hindbrain. PMID- 26131858 TI - Solar ultraviolet radiation: properties, characteristics and amounts observed in Brazil and South America. AB - The beneficial and harmful effects of human exposure to solar ultraviolet radiation (UV-R) are topics that arouse great interest not only among physicians and scientists, but also the general public and the media. Currently, discussions on vitamin D synthesis (beneficial effect) are confronted with the high and growing number of new cases of non-melanoma skin cancer and other diseases of the skin and eyes (harmful effect) diagnosed each year in Brazil. However, the lack of scientific knowledge on the UV-R in Brazil and South America leads to adoption of protective measures based on studies conducted in Europe and USA, where the amounts of UV-R available at surface and the sun-exposure habits and characteristics of the population are significantly different from those observed in Brazil. In order to circumvent this problem, the Brazilian Society of Dermatology recently published the Brazilian Consensus of Photoprotection based on recent studies performed locally. The main goal of this article is to provide detailed educational information on the main properties and characteristics of UV R and UV index in a simple language. It also provides: a) a summary of UV-R measurements recently performed in Brazil; b) a comparison with those performed in Europe; and, c) an evaluation to further clarify the assessment of potential harm and health effects owing to chronic exposures. PMID- 26131859 TI - Nail involvement in adult patients with plaque-type psoriasis: prevalence and clinical features. AB - BACKGROUND: Psoriasis is a disease of worldwide distribution with a prevalence of 1 to 3%. Nail psoriasis is estimated in 50% of patients with psoriasis, and in the presence of joint involvement, it can reach 80%. OBJECTIVE: To study the nail changes - and their clinical implications - presented by patients with psoriasis vulgaris under surveillance in a university hospital from the south of Brazil. METHODS: his cross-sectional study evaluated 65 adult patients from January 2012 to March 2013. Cutaneous severity was assessed according to the Psoriasis Area and Severity Index (PASI). The Nail Psoriasis Severity Index (NAPSI) was used to evaluate patient's nails. The diagnosis of psoriatic arthritis was established according to the Classification Criteria for Psoriatic Arthritis (CASPAR). RESULTS: The prevalence of NP was 46.1%. These patients had a median [interquartilic range (IQR)] NAPSI of 1 (0-15). A total of 63.3% of patients reported aesthetic discomfort or functional impairment related to their nails. Onycholysis was the most common feature (80%). When compared with patients without nail involvement, patients with NP had lower mean age at psoriasis onset [21 (18-41) vs. 43 (30-56) years, p=0,001]; longer disease duration [15.5 (10-24) vs. 6 (2-12) years, p=0.001]; higher PASI [9.2 (5-17) vs. 3.7 (2-10), p=0.044], higher frequency of psoriatic arthritis (43.3 vs. 3.7, p = 0.002) and more often reported family history of psoriasis (40% vs. 7.4%, p = 0.011). CONCLUSION: Onycholysis was the most frequent finding and most patients feel uncomfortable with the psoriatic nail changes that they experience. PMID- 26131860 TI - Oral lichen planus: study of 21 cases. AB - BACKGROUND: Lichen planus is considered to be the most common dermatological disease involving the oral mucosa. OBJECTIVE: To investigate the profile, clinical features, and the presence of dysplasia and candidiasis in patients with oral lichen planus. METHODS: A total of 21 patients were selected from 258 patients at risk for oral cancer development. RESULTS: Most of the patients were white (76,2%), female (66,6%), with mean age of 58.8 years. Eight were smokers and seven were alcohol consumers. The buccal mucosa was the most affected site, followed by the tongue and the gingiva. The reticular pattern was the most common appearance. Histopathology depicted dysplasia in nine cases and cytopathology was positive for Candida in eight cases in the first appointment. CONCLUSION: Our data are similar to the literature. Cytopathology was important for the diagnosis of candidiasis. Although the presence of dysplasia was verified, further studies are necessary to clarify the importance of this finding. PMID- 26131861 TI - Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma. AB - BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHODS: Blood was obtained from ten patients with proved metastatic cutaneous melanoma (Group 1), 15 patients resected for cutaneous melanoma without metastasis (Group 2) and 5 healthy donors (Group 3). Melanoma inhibitory activity was measured using a commercially available ELISA kit. RESULTS: There was a statistically significant difference of Melanoma inhibitory activity levels between patients with and without metastasis (p=0.002), and between patients with metastasis and healthy donors (p=0.002). There was no difference between patients without metastasis and healthy donors (p=0.443). CONCLUSION: Melanoma inhibitory activity is a tumor marker for cutaneous melanoma and the Melanoma inhibitory activity-ELISA test can be easily performed. Patients with metastasis have increased Melanoma inhibitory activity serum levels when compared to patients without metastasis and healthy donors. PMID- 26131862 TI - Onychomycosis due to opportunistic molds. AB - BACKGROUND: Onychomycosis are caused by dermatophytes and Candida, but rarely by non- dermatophyte molds. These opportunistic agents are filamentous fungi found as soil and plant pathogens. OBJECTIVES: To determine the frequency of opportunistic molds in onychomycosis. METHODS: A retrospective analysis of 4,220 cases with onychomycosis, diagnosed in a 39-month period at the Institute of Dermatology and Skin surgery "Prof. Dr. Fernando A. Cordero C." in Guatemala City, and confirmed with a positive KOH test and culture. RESULTS: 32 cases (0.76%) of onychomycosis caused by opportunistic molds were confirmed. The most affected age group ranged from 41 to 65 years (15 patients, 46.9%) and females were more commonly affected (21 cases, 65.6%) than males. Lateral and distal subungual onychomycosis (OSD-L) was detected in 20 cases (62.5%). The microscopic examination with KOH showed filaments in 19 cases (59.4%), dermatophytoma in 9 cases (28.1%), spores in 2 cases (6.25%), and filaments and spores in 2 cases (6.25%). Etiologic agents: Aspergillus sp., 11 cases (34.4%); Scopulariopsis brevicaulis, 8 cases (25.0%); Cladosporium sp., 3 cases (9.4%); Acremonium sp., 2 cases (6.25%); Paecilomyces sp., 2 cases (6.25%); Tritirachium oryzae, 2 cases (6.25%); Fusarium sp., Phialophora sp., Rhizopus sp. and Alternaria alternate, 1 case (3.1%) each. CONCLUSIONS: We found onychomycosis by opportunistic molds in 0.76% of the cases and DLSO was present in 62.5%. The most frequent isolated etiological agents were: Aspergillus sp. and Scopulariopsis brevicaulis. PMID- 26131863 TI - Distribution pattern of psoriasis, anxiety and depression as possible causes of sexual dysfunction in patients with moderate to severe psoriasis. AB - BACKGROUND: Psoriasis may significantly impair sexual function. Depression and organic factors appear to play a key role in this relation. However, beyond genital psoriasis, the importance of the disease's distribution patterns has not been considered. OBJECTIVES: To research sexual function in psoriasis patients and investigate the roles of anxiety, depression and psoriasis' distribution patterns in sexual dysfunction. METHODS: A comparative study matched for sex and age was performed. Eighty patients with moderate to severe psoriasis and 80 healthy controls were included. The participants completed the Massachusetts General Hospital-Sexual Functioning Questionnaire, the Hospital Anxiety and Depression Scale, and the Self-Administered Psoriasis Area and Severity Index. RESULTS: Psoriasis was associated with sexual dysfunction, odds ratio=5.5 (CI 95% 2.6-11.3; p<0.001). Certain distribution patterns of psoriasis, involving specific body regions, were associated with an increase in sexual dysfunction in the group presenting the disease, odds ratio 7.9 (CI 95% 2.3-33.4; p<0.001). Multivariate logistic regression analysis identified anxiety and depression, and the involvement of these specific areas, as possible independent risk factors for sexual dysfunction in patients with moderate to severe psoriasis. CONCLUSION: This study identifies body areas potentially related to sexual dysfunction, independently of anxiety and depression, in psoriasis patients. The results suggest that the assessment of sexual dysfunction and the involvement of these body areas should be considered as disease severity criteria when choosing the treatment for psoriasis patients. PMID- 26131864 TI - Prolonged viability of human organotypic skin explant in culture method (hOSEC). AB - BACKGROUND: Currently, the cosmetic industry is overwhelmed in keeping up with the safety assessment of the increasing number of new products entering the market. To meet such demand, research centers have explored alternative methods to animal testing and also the large number of volunteers necessary for preclinical and clinical tests. OBJECTIVES: This work describes the human skin ex vivo model (hOSEC: Human Organotypic Skin Explant Culture) as an alternative to test the effectiveness of cosmetics and demonstrate its viability through cutaneous keratinocytes' proliferative capacity up to 75 days in culture. METHODS: The skin explants obtained from surgeries were cultured in CO2-humid incubator. After 1, 7, 30 and 75 days in culture, skin fragments were harvested for analysis with histomorphological exam (HE staining) on all days of follow-up and immunohistochemistry for Ck5/6, Ck10 and Ki-67 only on the 75th day. RESULTS: On the 7th day, the epidermis was perfect in the dermoepidermal junction, showing the viability of the model. On the 30th day, the epidermis was thicker, with fewer layers on the stratum corneum, although the cutaneous structure was unaltered. On the 75th day, the skin became thinner but the dermoepidermal junctions were preserved and epidermal proliferation was maintained. After the 75th day on culture, the skin was similar to normal skin, expressing keratinocytes with Ck5/6 on supra-basal layers; Ck10 on differentiated layers; and viability could be assessed by the positivity of basal cells by Ki-67. CONCLUSION: The hOSEC model seems a good alternative to animal testing; it can be used as a preclinical test analogous to clinical human skin test with similar effectiveness and viability proven by immunohistological analyses. PMID- 26131865 TI - The relation between dermoscopy and histopathology of basal cell carcinoma. AB - BACKGROUND: Basal cell carcinoma is the most frequent cancer in fair-skinned populations and dermoscopy is an important, non-invasive technique that aids in the diagnosis of Basal cell carcinoma. OBJECTIVES: The aim of this study was to evaluate the relationship between histopathological subtypes and dermoscopic features of Basal cell carcinoma. METHODS: This study included 98 patients with clinically and histopathologically confirmed Basal cell carcinomas. The dermoscopic features of the lesions from each patient were analyzed before the histopathological findings were evaluated. RESULTS: Dermoscopic structures were observed in all 98 patients and irregular vascularity was identified in 78 patients (79.6%). The most common vascular pattern was the presence of arborizing vessels (42 patients, 42.9%) followed by arborizing microvessels (21 patients, 21.4%) and short fine telangiectasias (SFTs; 15 patients, 15.3%). White streaks (38 patients, 38.8%), translucency (31 patients, 31.6%), a milky-pink to red background (42 patients, 42.9%), and erosion/ulceration (29 patients, 29.6%) were also observed. Pigmented islands were seen as blue-gray globules (7 patients, 7.1%) and blue-gray ovoid nests (42 patients, 42.9%). The pigment distribution pattern was maple leaf-like areas in 9 patients (9.2 %) and spoke wheel-like areas in 6 patients (6.1%). CONCLUSIONS: Basal cell carcinomas show a wide spectrum of dermoscopic features. Arborizing vessels were the most common dermoscopic findings in Basal cell carcinomas, while superficial Basal cell carcinomas displayed mainly milky-pink to red areas, and arborizing microvessels. The most common dermoscopic features of pigmented types were islands of pigment (blue-gray globules, blue-gray ovoid nests). In conclusion, dermoscopy can be used as a valuable tool for the diagnosis of Basal cell carcinomas and prediction of their histopathological subtypes. PMID- 26131866 TI - Translation, cross-cultural adaptation and validation of the vitiligo-specific health-related quality of life instrument (VitiQoL) into Brazilian Portuguese. AB - BACKGROUND: Vitiligo, although asymptomatic, highly compromises patients' quality of life (QoL). Therefore, an adequate evaluation of QoL is essential. OBJECTIVES: Translation, cultural adaptation and validation of VitiQol (Vitiligo-specific health-related quality of life instrument) into Brazilian Portuguese. METHODS: The study was conducted in two stages; the first stage was the translation and cultural/linguistic adaptation of the instrument; the second stage was the instrument's validation. RESULTS: The translated VitiQol showed high internal consistency (Cronbach alpha = 0.944) and high test-retest reliability and intraclass correlation coefficient=0.95 (CI 95% 0.86 - 0.98), p<0.001. There was no statistically significant difference between the means of the first completion of the VitiQoL questionnaire and the retest, p = 0.661. There was a significant correlation between VitiQoL and DLQI (r = 0.776, p <0.001) and also between VitiQoL-PB and subjects' assessment of the severity of their disease (r = 0.702, p <0.001). CONCLUSIONS: The impact of vitiligo on the QoL of Brazilian patients can be assessed by a specific questionnaire. PMID- 26131867 TI - Henrique da Rocha Lima. AB - Brazilian physician and researcher Henrique da Rocha Lima was born in 1879 in the city of Rio de Janeiro, where he studied medicine and obtained the degree of M.D. in 1901. He specialized in Clinical Medicine in Germany and was the ambassador in European countries of the scientific medicine that emerged from the Oswaldo Cruz Institute in the early twentieth century. Rocha Lima has discovered the causative agent of typhus and had a major contribution to the studies of yellow fever, Chagas disease, Carrion's disease and histoplasmosis. His genius, his research and his discoveries projected his name, and, with it, the image of Brazil in the international scientific scene. PMID- 26131868 TI - Treatment of psoriasis and psoriatic arthritis during pregnancy and breastfeeding. AB - Psoriasis is a chronic inflammatory disease that affects primarily the skin and joints, with a worldwide incidence of 2-3%. Fifty percent of patients are women, most still diagnosed during childbearing years. Currently,the estimate is that up to 107 thousand deliveries are performed annually in women with psoriasis, a percentage of them in women with moderate to severe disease. Fetal risks in pregnant women with psoriasis derive both from maternal disease and the medications used to control the illness. The purpose of this review is to study the effect of the main drugs used in the treatment of psoriasis and psoriatic arthritis during pregnancy and lactation, with particular focus on disease modifying anti-rheumatic biological drugs, biological therapies, immunobiologics or biologics. PMID- 26131870 TI - Histopathological analysis of the therapeutic response to cryotherapy with liquid nitrogen in patients with multiple actinic keratosis. AB - Actinic keratoses are premalignant lesions of the skin caused by excessive sun exposure. Lesions may become mainly squamous cell carcinoma. Cryotherapy with liquid nitrogen is one of the main treatments. In order to evaluate the response of actinic keratosis to cryotherapy by histopathology, two lesions were selected in each of 14 patients with multiple actinic keratoses. In one lesion a biopsy was performed and in the other lesion a biopsy was performed after cryotherapy. Subsequently, both biopsies were compared histologically. Of the thirteen patients who completed the study, the best results were obtained in lesions undergoing cryotherapy concerning the atypia of keratinocytes, epithelial thickness and corneal layer and lymphocytic infiltrate. Despite the small number of patients, it was concluded that, if performed correctly, cryotherapy has high efficacy in the treatment of actinic keratoses. PMID- 26131869 TI - Surgical treatment of basal cell carcinoma: an algorithm based on the literature. AB - Although basal cell carcinoma can be effectively managed through surgical excision, the most suitable surgical margins have not yet been fully determined. Furthermore, micrographic surgery is not readily available in many places around the world. A review of the literature regarding the surgical treatment of basal cell carcinoma was conducted in order to develop an algorithm for the surgical treatment of basal cell carcinoma that could help the choice of surgical technique and safety margins, considering the major factors that affect cure rates. Through this review, it was found that surgical margins of 4mm seem to be suitable for small, primary, well-defined basal cell carcinomas, although some good results can be achieved with smaller margins and the use of margin control surgical techniques. For treatment of high-risk and recurrent tumors, margins of 5-6 mm or margin control of the surgical excision is required. Previous treatment, histological subtype, site and size of the lesion should be considered in surgical planning because these factors have been proven to affect cure rates. Thus, considering these factors, the algorithm can be a useful tool, especially for places where micrographic surgery is not widely available. PMID- 26131871 TI - Interstitial granulomatous dermatitis: rare cutaneous manifestation of rheumatoid arthritis. AB - Besides being an uncommon clinicopathological entity, interstitial granulomatous dermatitis, also described as interstitial granulomatous dermatitis with arthritis (IGDA), has shown a wide spectrum of clinical manifestations, such as linear and erythematous lesions, papules, plaques and nodules. Histological features include dense dermal histiocytic infiltrate, usually in a palisade configuration, and scattered neutrophils and eosinophils. We describe a middle aged woman with rheumatoid arthritis of difficult management and cutaneous lesions compatible with IGDA. PMID- 26131872 TI - Esophageal lichen planus. AB - Lichen planus is a chronic inflammatory disease that affects the skin, mucous membranes, nails and scalp. Esophageal lichen planus is a rarely reported manifestation of lichen planus, presenting itself commonly in middle-aged women, with symptoms such as dysphagia. We report a case of esophageal lichen planus in a 54-year-old woman associated with oral, cutaneous and ungual lichen planus. Although lichen planus is a disorder well known by dermatologists, reports of esophageal lichen planus are rare in dermatologic literature. The esophageal lichen planus is little known and underdiagnosed, with a significant delay between the onset of symptoms and diagnosis. PMID- 26131873 TI - Traumatic neuroma of the penis after circumcision--Case report. AB - Traumatic neuromas are tumors resulting from hyperplasia of axons and nerve sheath cells after section or injury to the nervous tissue. We present a case of this tumor, confirmed by anatomopathological examination, in a male patient with history of circumcision. Knowledge of this entity is very important in achieving the differential diagnosis with other lesions that affect the genital area such as condyloma acuminata, bowenoid papulosis, lichen nitidus, sebaceous gland hyperplasia, achrochordon and pearly penile papules. PMID- 26131874 TI - Brachioradial pruritus in a patient with cervical disc herniation and Parsonage Turner syndrome. AB - Brachioradial pruritus is a chronic sensory neuropathy of unknown etiology which affects the skin of the shoulders, arms and forearms on the insertion of the brachioradialis muscle. We describe the case of a 60-year old woman recently diagnosed with multiple myeloma who refers paresis, severe pruritus and itching lesions on the right arm with 6 months of evolution. Investigation led to a diagnosis of Brachioradial pruritus consequent to the presence of cervical disc herniation and Parsonage-Turner syndrome. The patient started gabapentin 900 mg/day with good control of itching. Corticosteroids and antihistamines are often ineffective in the treatment of BP. Gabapentin has been used with encouraging results. All patients with Brachioradial pruritus should be evaluated for cervical spine injuries. PMID- 26131875 TI - Atypical infantile genital Molluscum contagiosum. AB - Genital molluscum contagiosum is rare in children. We report a molluscum contagiosum around the vulva and anus of 9-year-old girl, which has atypical presentations and was finally confirmed by histopathological and electron microscopy findings. PMID- 26131876 TI - Milker's nodule--Case report. AB - Milker's nodule is an occupational viral skin disease of universal distribution, caused by the Paravaccinia virus and that occurs in individuals who deal with dairy cattle herds. We describe a case acquired due to lack of use of PPE (Personal Protective Equipment) and perform a literature review. PMID- 26131877 TI - Reflectance confocal microscopy of cutaneous melanoma. Correlation with dermoscopy and histopathology. AB - In vivo Confocal Microscopy is a method for non-invasive, real-time visualization of microscopic structures and cellular details of the epidermis and dermis, which has a degree of resolution similar to that obtained with histology. We present a case of cutaneous melanoma in which diagnosis was aided by confocal microscopy examination. We also correlate the observed features with the dermoscopic and histopathological findings. Confocal microscopy proved to be an useful adjunct to dermoscopy, playing an important role as a method 'between clinical evaluation and histopathology'. PMID- 26131878 TI - Phenotypic spectrum of a patient with Gorlin's syndrome and role of dermoscopy in the early detection of basal cell carcinomas. AB - Gorlin's syndrome is an autosomal dominant disorder, mainly characterized by the presence of multiple and early-onset basal cell carcinomas, odontogenic keratocysts and palmoplantar pits. We describe the case of a patient with clinical and imaging features of Gorlin syndrome, and highlight the role of dermoscopy in the early detection of basal cell carcinomas. In addition, we discuss the dermoscopic features of palmar pits. PMID- 26131879 TI - Tuberculoid leprosy presenting as a "racket" lesion. AB - The "racket" lesion is a rare presentation of tuberculoid leprosy, which consists of a thickened nerve branch emerging from a tuberculoid plaque. It results from centripetal damage to cutaneous nerves caused by granuloma formation. We describe a typical case of tuberculoid leprosy presenting as a "racket" lesion. The lesion persisted after treatment with paucibacillary multidrug therapy. PMID- 26131880 TI - Syndrome in Question. AB - The Iso-Kikuchi Syndrome is a rare condition characterized by nail dysplasia involving the index fingers, including micronychia, polyonychia, anonychia, irregular lunula, malalignment and hemionychogryphosis. On the antero-posterior image, radiologic examination reveals a narrowing of the distal phalanx. The lateral image shows a Y-shaped bifurcation of the distal phalanx. We report a case of a patient with typical clinical and radiologic signs of Iso-Kikuchi Syndrome. PMID- 26131881 TI - Evaluation of the therapeutic results of actinic keratosis treated with topical 5% fluorouracil by reflectance confocal laser microscopy: preliminary study. AB - Topical treatment for actinic keratosis with 5% fluorouracil has a recurrence rate of 54% in 12 months of follow-up. This study analyzed thirteen actinic keratoses on the upper limbs through confocal microscopy, at the time of clinical diagnosis and after 4 weeks of treatment with fluorouracil. After the treatment was established and evidence of clinical cure was achieved, in two of the nine actinic keratoses, confocal microscopy enabled visualization of focal areas of atypical honeycomb pattern in the epidermis indicating therapeutic failure. Preliminary data suggest the use of confocal microscopy as a tool for diagnosis and therapeutic control of actinic keratosis. PMID- 26131883 TI - Cleft-like appearance of accessory nipple in digital microscopy. PMID- 26131882 TI - Serum levels of 25-hydroxy vitamin D in psoriatic patients. AB - Studies have shown a relationship between vitamin D and psoriasis. We compared serum levels of vitamin D of 20 psoriasis patients and 20 controls. The median vitamin D level was 22.80 +/- 4.60 ng/ml; the median in the cases was 23.55 +/- 7.6 ng/ml, and in controls 22.35 +/- 3.10 ng/ml (p = 0.73). Only 2 cases and 4 controls had sufficient levels of vitamin D, although without statistical significance between the groups (p = 0.608). Levels were lower in women with psoriasis compared with those in male patients (20.85 +/- 6.70 x 25.35 +/- 2.90 ng/ml, p = 0.03), a finding that was not observed among controls. PMID- 26131884 TI - Comments on the article: "Update on therapy for superficial mycoses: review article part I". PMID- 26131885 TI - Counter-reply. PMID- 26131886 TI - American cutaneous leishmaniasis in Brazil. PMID- 26131887 TI - Vascular regulation via KIR channels and Na(+)/K(+)-ATPase. PMID- 26131888 TI - Prevalence and Social Determinants of Smoking in 15 Countries from North Africa, Central and Western Asia, Latin America and Caribbean: Secondary Data Analyses of Demographic and Health Surveys. AB - BACKGROUND: Article 20 of the World Health Organisation Framework Convention on Tobacco Control calls for a cross-country surveillance of tobacco use through population-based surveys. We aimed to provide country-level prevalence estimates for current smoking and current smokeless tobacco use and to assess social determinants of smoking. METHODS: Data from Demographic and Health Surveys done between 2005 and 2012, among men and women from nine North African, Central and West Asian countries and six Latin American and Caribbean countries were analyzed. Weighted country-level prevalence rates were estimated for 'current smoking' and 'current use of smokeless tobacco (SLT) products' among men and women. In each country, social determinants of smoking among men and women were assessed by binary logistic regression analyses by including men's and women's sampling weights to account for the complex survey design. FINDINGS: Prevalence of smoking among men was higher than 40% in Armenia (63.1%), Moldova (51.1%), Ukraine (52%), Azerbaijan (49.8 %), Kyrgyz Republic (44.3 %) and Albania (42.52%) but the prevalence of smoking among women was less than 10% in most countries except Ukraine (14.81%) and Jordan (17.96%). The prevalence of smokeless tobacco use among men and women was less than 5% in all countries except among men in the Kyrgyz Republic (10.6 %). Smoking was associated with older age, lower education and poverty among men and higher education and higher wealth among women. Smoking among both men and women was associated with unskilled work, living in urban areas and being single. CONCLUSION: Smoking among men was very high in Central and West Asian countries. Social pattern of smoking among women that was different from men in education and wealth should be considered while formulating tobacco control policies in some Central and West Asian countries. PMID- 26131889 TI - Propensity of Self-Assembled Leucine-Lysine Diblock Copolymeric alpha-Helical Peptides To Remain in Parallel and Antiparallel Alignments in Water. AB - Molecular dynamics simulation study of alpha-helical diblock copolypeptides preassembled in parallel and antiparallel alignments in water are presented. The assembled peptide lamellar structures were not disrupted even after performing three-step simulation protocols. Primarily hydrogen bonds between peptide are responsible for the stability. The analysis of the trajectory also suggests that water plays a significant role in favoring self-assembly. We have detected continuous hydrogen bonded network structure, which is further responsible for the stability of the lamellar structures. We have performed a detailed analysis of the hydrogen bonded network structure and its length. Further, free energy calculations revealed that the degree of stability for both lamellae are similar. The present study provides structural insight into the stability of self assembled structures of block copolypeptides. PMID- 26131890 TI - Exploiting Task Constraints for Self-Calibrated Brain-Machine Interface Control Using Error-Related Potentials. AB - This paper presents a new approach for self-calibration BCI for reaching tasks using error-related potentials. The proposed method exploits task constraints to simultaneously calibrate the decoder and control the device, by using a robust likelihood function and an ad-hoc planner to cope with the large uncertainty resulting from the unknown task and decoder. The method has been evaluated in closed-loop online experiments with 8 users using a previously proposed BCI protocol for reaching tasks over a grid. The results show that it is possible to have a usable BCI control from the beginning of the experiment without any prior calibration. Furthermore, comparisons with simulations and previous results obtained using standard calibration hint that both the quality of recorded signals and the performance of the system were comparable to those obtained with a standard calibration approach. PMID- 26131891 TI - Correction: Measurement of Mandibular Growth Using Cone-Beam Computed Tomography: A Miniature Pig Model Study. PMID- 26131893 TI - Accessible atomic structures from sub-micron protein crystals. PMID- 26131892 TI - Isolation and Host Range of Bacteriophage with Lytic Activity against Methicillin Resistant Staphylococcus aureus and Potential Use as a Fomite Decontaminant. AB - Staphylococcus aureus (SA) is a commensal bacterium and opportunistic pathogen commonly associated with humans and is capable of causing serious disease and death including sepsis, pneumonia, and meningitis. Methicillin-resistant SA (MRSA) isolates are typically resistant to many available antibiotics with the common exception of vancomycin. The presence of vancomycin resistance in some SA isolates combined with the current heavy use of vancomycin to treat MRSA infections indicates that MRSA may achieve broad resistance to vancomycin in the near future. New MRSA treatments are clearly needed. Bacteriophages (phages) are viruses that infect bacteria, commonly resulting in death of the host bacterial cell. Phage therapy entails the use of phage to treat or prevent bacterial infections. In this study, 12 phages were isolated that can replicate in human SA and/or MRSA isolates as a potential way to control these infections. 5 phage were discovered through mitomycin C induction of prophage and 7 others as extracellular viruses. Primary SA strains were also isolated from environmental sources to be used as tools for phage discovery and isolation as well as to examine the target cell host range of the phage isolates by spot testing. Primary isolates were tested for susceptibility to oxacillin in order to determine which were MRSA. Experiments were performed to assess the host range and killing potential of newly discovered phage, and significant reductions in bacterial load were detected. We explored the utility of some phage to decontaminate fomites (glass and cloth) and found a significant reduction in colony forming units of MRSA following phage treatment, including tests of a phage cocktail against a cocktail of MRSA isolates. Our findings suggest that phage treatment can be used as an effective tool to decontaminate human MRSA from both hard surfaces and fabrics. PMID- 26131895 TI - Diaphony, a measure of uniform distribution, and the Patterson function. AB - This paper reviews the number-theoretic concept of diaphony, a measure of uniform distribution for number sequences and point sets based on a Fourier theory approach, and its relation to crystallographic concepts like the largest interplanar spacing of a lattice, the structure-factor equation and the Patterson function. PMID- 26131894 TI - MicroED data collection and processing. AB - MicroED, a method at the intersection of X-ray crystallography and electron cryo microscopy, has rapidly progressed by exploiting advances in both fields and has already been successfully employed to determine the atomic structures of several proteins from sub-micron-sized, three-dimensional crystals. A major limiting factor in X-ray crystallography is the requirement for large and well ordered crystals. By permitting electron diffraction patterns to be collected from much smaller crystals, or even single well ordered domains of large crystals composed of several small mosaic blocks, MicroED has the potential to overcome the limiting size requirement and enable structural studies on difficult-to crystallize samples. This communication details the steps for sample preparation, data collection and reduction necessary to obtain refined, high-resolution, three dimensional models by MicroED, and presents some of its unique challenges. PMID- 26131896 TI - Algorithm for systematic peak extraction from atomic pair distribution functions. AB - The study presents an algorithm, ParSCAPE, for model-independent extraction of peak positions and intensities from atomic pair distribution functions (PDFs). It provides a statistically motivated method for determining parsimony of extracted peak models using the information-theoretic Akaike information criterion (AIC) applied to plausible models generated within an iterative framework of clustering and chi-square fitting. All parameters the algorithm uses are in principle known or estimable from experiment, though careful judgment must be applied when estimating the PDF baseline of nanostructured materials. ParSCAPE has been implemented in the Python program SrMise. Algorithm performance is examined on synchrotron X-ray PDFs of 16 bulk crystals and two nanoparticles using AIC-based multimodeling techniques, and particularly the impact of experimental uncertainties on extracted models. It is quite resistant to misidentification of spurious peaks coming from noise and termination effects, even in the absence of a constraining structural model. Structure solution from automatically extracted peaks using the Liga algorithm is demonstrated for 14 crystals and for C60. Special attention is given to the information content of the PDF, theory and practice of the AIC, as well as the algorithm's limitations. PMID- 26131897 TI - Approximation of virus structure by icosahedral tilings. AB - Viruses are remarkable examples of order at the nanoscale, exhibiting protein containers that in the vast majority of cases are organized with icosahedral symmetry. Janner used lattice theory to provide blueprints for the organization of material in viruses. An alternative approach is provided here in terms of icosahedral tilings, motivated by the fact that icosahedral symmetry is non crystallographic in three dimensions. In particular, a numerical procedure is developed to approximate the capsid of icosahedral viruses by icosahedral tiles via projection of high-dimensional tiles based on the cut-and-project scheme for the construction of three-dimensional quasicrystals. The goodness of fit of our approximation is assessed using techniques related to the theory of polygonal approximation of curves. The approach is applied to a number of viral capsids and it is shown that detailed features of the capsid surface can indeed be satisfactorily described by icosahedral tilings. This work complements previous studies in which the geometry of the capsid is described by point sets generated as orbits of extensions of the icosahedral group, as such point sets are by construction related to the vertex sets of icosahedral tilings. The approximations of virus geometry derived here can serve as coarse-grained models of viral capsids as a basis for the study of virus assembly and structural transitions of viral capsids, and also provide a new perspective on the design of protein containers for nanotechnology applications. PMID- 26131898 TI - Pairwise correlations in layered close-packed structures. AB - Given a description of the stacking statistics of layered close-packed structures in the form of a hidden Markov model, analytical expressions are developed for the pairwise correlation functions between the layers. These may be calculated analytically as explicit functions of model parameters or the expressions may be used as a fast, accurate and efficient way to obtain numerical values. Several examples are presented, finding agreement with previous work as well as deriving new relations. PMID- 26131899 TI - Topological crystallography of gas hydrates. AB - A new approach to the investigation of the proton-disordered structure of clathrate hydrates is presented. This approach is based on topological crystallography. The quotient graphs were built for the unit cells of the cubic structure I and the hexagonal structure H. This is a very convenient way to represent the topology of a hydrogen-bonding network under periodic boundary conditions. The exact proton configuration statistics for the unit cells of structure I and structure H were obtained using the quotient graphs. In addition, the statistical analysis of the proton transfer along hydrogen-bonded chains was carried out. PMID- 26131900 TI - Iterative projection algorithms in protein crystallography. II. Application. AB - Iterative projection algorithms (IPAs) are a promising tool for protein crystallographic phase determination. Although related to traditional density modification algorithms, IPAs have better convergence properties, and, as a result, can effectively overcome the phase problem given modest levels of structural redundancy. This is illustrated by applying IPAs to determine the electron densities of two protein crystals with fourfold non-crystallographic symmetry, starting with only the experimental diffraction amplitudes, a low resolution molecular envelope and the position of the non-crystallographic axes. The algorithm returns electron densities that are sufficiently accurate for model building, allowing automated recovery of the known structures. This study indicates that IPAs should find routine application in protein crystallography, being capable of reconstructing electron densities starting with very little initial phase information. PMID- 26131901 TI - Temperature- and energy-dependent phase shifts of resonant multiple-beam X-ray diffraction in germanium crystals. AB - This paper reports temperature- and energy-dependent phase shifts of resonant multiple-beam X-ray diffraction in germanium crystals, involving forbidden (002) and weak (222) reflections. Phase determination based on multiple-beam diffraction is employed to estimate phase shifts from (002)-based {(002)(375)(373)} four-beam cases and (222)-based { (222)(533)} three-beam cases in the vicinity of the Ge K edge for temperatures from 20 K up to 300 K. The forbidden/weak reflections enhance the sensitivity of measuring phases at resonance. At room temperature, the resonance triplet phases reach a maximum of 8 degrees for the four-beam cases and -19 degrees for the three-beam cases. It is found that the peak intensities and triplet phases obtained from the (002) four beam diffraction are related to thermal motion induced anisotropy and anomalous dispersion, while the (222) three-beam diffraction depends on the aspherical covalent electron distribution and anomalous dispersion. However, the electron phonon interaction usually affects the forbidden reflections with increasing temperatures and seems to have less effect on the resonance triplet phase shifts measured from the (002) four-beam diffraction. The resonance triplet phase shifts of the (222) three-beam diffraction versus temperature are also small. PMID- 26131902 TI - The atomic anisotropic displacement tensor - completing the picture. AB - A simplified approach for calculating the equivalent isotropic displacement parameter is presented and the transformation property of the tensor representation U to point-group operations is analysed. Complete tables have been compiled for the restrictions imposed upon the tensor owing to the site symmetry associated with all special positions as listed in Hahn [(2011), International Tables for Crystallography, Vol. A, Space-group Symmetry, 5th revised ed. Chichester: John Wiley and Sons, Ltd]. PMID- 26131904 TI - Expression of Ik6 and Ik8 Isoforms and Their Association with Relapse and Death in Mexican Children with Acute Lymphoblastic Leukemia. AB - Expression of the 6 and 8 dominant-negative Ikaros isoforms in pediatric patients with acute lymphoblastic leukemia has been associated with a high risk of relapse and death; due to these isoforms disrupting the differentiation and proliferation of lymphoid cells. The aim of this study was to know the frequency of Ik6 and Ik8 in 113 Mexican ALL-children treated within the National Popular Medical Insurance Program to determine whether there was an association with relapse-free survival, event-free survival and overall survival, and to assess its usefulness in the initial stratification of patients. The expression of these isoforms was analyzed using specific primer sets and nested RT-PCR. The detected transcripts were classified according to the isoforms's sizes reported. A non-expected band of 300 bp from one patient was analyzed by sequencing. Twenty-six patients expressed Ik6 and/or Ik8 and one of them expressed a variant of Ik8 denominated Ik8-deleted. Although the presence of them was not statistically associated with lower relapse free survival (p = 0.432), event free survival (p = 0.667) or overall survival (p = 0.531), inferior overall survival was observed in patients that expressed these isoforms and showed high or standard risk by age and white blood-cell count at diagnosis. Of the 26 patients Ik6+ and/or Ik8+, 14 did not present adverse events; from them 6 were exclusively Ik6+ and/or Ik8+, and 8 were positive for the other Ikaros isoforms (Ik1, Ik2, Ik5, Ik3A, Ik4, Ik4A, Ik7). In the patients studied, the expression of Ik6 and Ik8 did not constitute an independent prognostic factor for relapse or death related to disease; therefore, they could not be used in the initial risk stratification. PMID- 26131905 TI - iTRAQ-Based Quantitative Proteomic Analysis of the Initiation of Head Regeneration in Planarians. AB - The planarian Dugesia japonica has amazing ability to regenerate a head from the anterior ends of the amputated stump with maintenance of the original anterior posterior polarity. Although planarians present an attractive system for molecular investigation of regeneration and research has focused on clarifying the molecular mechanism of regeneration initiation in planarians at transcriptional level, but the initiation mechanism of planarian head regeneration (PHR) remains unclear at the protein level. Here, a global analysis of proteome dynamics during the early stage of PHR was performed using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics strategy, and our data are available via ProteomeXchange with identifier PXD002100. The results showed that 162 proteins were differentially expressed at 2 h and 6 h following amputation. Furthermore, the analysis of expression patterns and functional enrichment of the differentially expressed proteins showed that proteins involved in muscle contraction, oxidation reduction and protein synthesis were up-regulated in the initiation of PHR. Moreover, ingenuity pathway analysis showed that predominant signaling pathways such as ILK, calcium, EIF2 and mTOR signaling which were associated with cell migration, cell proliferation and protein synthesis were likely to be involved in the initiation of PHR. The results for the first time demonstrated that muscle contraction and ILK signaling might played important roles in the initiation of PHR at the global protein level. The findings of this research provide a molecular basis for further unraveling the mechanism of head regeneration initiation in planarians. PMID- 26131906 TI - Successive Generations in a Rat Model Respond Differently to a Constant Obesogenic Environment. AB - Research has shown that if a mother experiences a transitory perturbation to her environment during pregnancy or lactation, there are transgenerational consequences often involving a disordered metabolic phenotype in first generation offspring with recovery across subsequent generations. In contrast, little is known about the nature of the transgenerational response of offspring when a mother experiences a perturbation that is not transitory but instead persists across generations. Our study, using a rat model, subjected the parental generation to a change in environment and concomitant shift from a grain-based to obesogenic diets to generate an adipose phenotype in first generation offspring emulating a common scenario in human urbanisation and migration. We then investigated whether the obese phenotype was stable across generations when maintained in the transitioned environment, and whether dietary macronutrient balance affected the response. We found that second and third generation offspring had a reduced body fat to lean mass ratio and a reduced appetite relative to first generation offspring, irrespective of dietary macronutrient balance. The trajectory of this response is suggestive of a reduction in chronic disease risk across generations. This is one of the first studies, to our knowledge, to investigate the transgenerational response following parental transition to a persistent obesogenic environment, and to demonstrate that successive generations respond differently to this constant environment. PMID- 26131909 TI - Correlation between band alignment and enhanced photocatalysis: a case study with anatase/TiO2(B) nanotube heterojunction. AB - It has long been known that efficient interfacial charge transfer between different phases of TiO2 is beneficial for enhanced photocatalysis. However, there has been considerable debate over the direction of the charge transfer across the interface of the different TiO2 phases. In this work, we study the case of TiO2 with a novel anatase/TiO2(B) heterojunction (ABHJ), wherein charge carrier transfer across the heterojunction interface is intensively investigated. The ABHJ is prepared by a two-step alkaline hydrothermal route and features nanotubes with a large surface area. Comprehensive analysis including UV-Vis-DRS, XPS, Mott-Schottky measurements, EPR and transient photovoltage techniques provides evidence for a type II band alignment in the ABHJ and migration of the photogenerated electrons from anatase to TiO2(B), which could effectively inhibit the recombination rate of photo-induced electron-hole pairs. Photocatalytic tests demonstrate that the as-obtained ABHJ shows higher activity than both the single phase and P25, not only for hydrogen production, but also for the photodegradation of gaseous acetaldehyde, which is due to the synergistic effect between an efficient charge separation at the interface and a high surface area. PMID- 26131907 TI - A Conserved Pattern of Primer-Dependent Transcription Initiation in Escherichia coli and Vibrio cholerae Revealed by 5' RNA-seq. AB - Transcription initiation that involves the use of a 2- to ~4-nt oligoribonucleotide primer, "primer-dependent initiation," (PDI) has been shown to be widely prevalent at promoters of genes expressed during the stationary phase of growth in Escherichia coli. However, the extent to which PDI impacts E. coli physiology, and the extent to which PDI occurs in other bacteria is not known. Here we establish a physiological role for PDI in E. coli as a regulatory mechanism that modulates biofilm formation. We further demonstrate using high throughput sequencing of RNA 5' ends (5' RNA-seq) that PDI occurs in the pathogenic bacterium Vibrio cholerae. A comparative global analysis of PDI in V. cholerae and E. coli reveals that the pattern of PDI is strikingly similar in the two organisms. In particular, PDI is detected in stationary phase, is not detected in exponential phase, and is preferentially apparent at promoters carrying the sequence T-1A+1 or G-1G+1 (where position +1 corresponds to the position of de novo initiation). Our findings demonstrate a physiological role for PDI and suggest PDI may be widespread among Gammaproteobacteria. We propose that PDI in both E. coli and V. cholerae occurs though a growth phase-dependent process that leads to the preferential generation of the linear dinucleotides 5' UA-3' and 5'-GG-3'. PMID- 26131910 TI - Intravoxel Incoherent Motion Diffusion-weighted Imaging of Multiple Myeloma Lesions: Correlation with Whole-Body Dynamic Contrast Agent-enhanced MR Imaging. AB - PURPOSE: To correlate intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters with the enhancement patterns of bone marrow and focal lesion obtained on whole-body (WB) dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) images in patients with stage-III multiple myeloma (MM) before and after systemic therapy. MATERIALS AND METHODS: Twenty-seven patients with MM were retrospectively included in this institutional review board-approved study. Requirement for written informed consent was waived. All patients underwent WB DCE MR imaging before treatment and 18 patients underwent repeat MR imaging 3 months after treatment. A transverse IVIM DWI sequence with 10 b values (0, 10, 20, 30, 50, 80, 100, 200, 400, and 800 sec/mm(2)) was acquired within bone marrow and focal lesions. The IVIM parameters (perfusion fraction [f], molecular diffusion coefficient [D], and perfusion-related D [D*]) and apparent diffusion coefficient (ADC) were extracted for both focal lesions and bone marrow and correlated with focal lesions and maximal bone marrow enhancement (BMEmax) (Spearman correlation coefficient) at baseline and at follow-up (Wilcoxon signed rank test). RESULTS: D and ADC values positively correlated with BMEmax (r = 0.7, P < .001; and r = 0.455, P = .0435, respectively). Patients with increased BMEmax showed significantly increased ADC and D within bone marrow versus patients who did not have increased BMEmax (ADC, 0.67 * 10(-3) mm(2)/sec vs 0.54 * 10(-3) mm(2)/sec, P = .03; D, 0.58 * 10(-3) mm(2)/sec vs 0.42 * 10(-3) mm(2)/sec, P < .001). Within focal lesions, f was the maximum in lesions that showed enhancement followed by washout. After treatment in good responders, the significant decrease in maximal enhancement value of focal lesions (baseline vs after treatment, 213.9% +/- 78.7 [standard deviation] vs 131% +/- 53.6, respectively; P < .001) was accompanied by a significant decrease in f (baseline vs after treatment, 11% +/- 3.8 vs 5.8% +/- 4.7, respectively; P < .001). CONCLUSION: Diffuse bone marrow involvement is associated with increased D. Hypervascular focal lesions with high maximal enhancement value of focal lesions also show high f value. Likewise, the decreased maximal enhancement value of focal lesions after treatment is accompanied by decreased f. PMID- 26131911 TI - Hepatocellular Carcinoma: A Phase II Randomized Controlled Double-Blind Trial of Transarterial Chemoembolization in Combination with Biweekly Intravenous Administration of Bevacizumab or a Placebo. AB - PURPOSE: To investigate the efficacy and safety of conventional transarterial chemoembolization (TACE) (cTACE) in combination with bevacizumab or a placebo in patients with hepatocellular carcinoma (HCC) in a randomized controlled double blind phase II trial. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained prior to inclusion. A total of 40 patients (20 patients per group, all 18 years or older) with histologically confirmed early- or intermediate-stage HCC and Child-Pugh class A or B cirrhosis were scheduled for inclusion. The primary endpoint was radiologic progression at 12 months according to European Association for the Study of the Liver criteria. Secondary endpoints were safety and overall survival (OS). Patients underwent cTACE with doxorubicin and intravenous administration of a placebo (cTACE-C) or bevacizumab (cTACE-B) (5 mg per kilogram of body weight) every 2 weeks for 52 weeks. After the first TACE procedure, TACE was repeated twice in 4-week intervals if indicated and technically feasible and on demand thereafter. Statistical analyses were performed with statistical software. P < .05 indicated a significant difference. RESULTS: Thirty-two patients were recruited between January 2006 and December 2009 (29 male, three female; mean age, 61 years +/- 8 [standard deviation]; Barcelona Clinic Liver Cancer stage A, n = 4; Barcelona Clinic Liver Cancer stage B, n = 28; predominant cause, alcohol [n = 15]; Child-Pugh class A disease, n = 22; Child-Pugh class B disease, n = 10; 16 patients received bevacizumab; 16 patients received a placebo). Patients underwent a median of three TACE cycles and received 13 infusions of bevacizumab versus 11 infusions of the placebo before the trial was stopped prematurely for safety reasons. Severe (grade 3-5) septic (n = 8 vs n = 3) and vascular (n = 9 vs n = 0) side effects were observed almost exclusively in the cTACE-B group. Median survival was worse in the cTACE-B group than in the cTACE-C group (5.3 vs 13.7 months; hazard ratio [HR], 1.7; 95% confidence interval [CI]: 0.8, 3.6; P = .195) and reached significance in patients with Child-Pugh class A cirrhosis (7.3 vs 26.5 months; HR, 2.6; 95% CI: 1.0, 6.6; P = .049). The primary endpoint was not met, since there was no difference in radiologic response between the groups at 3, 6, or 12 months. CONCLUSION: No improvement in radiologic tumor response or OS was observed in patients with HCC who received cTACE and bevacizumab, but severe and even lethal septic and vascular side effects occurred. Thus, bevacizumab cannot be recommended as an adjuvant treatment to cTACE. PMID- 26131912 TI - Superior Labral Cleft after Superior Labral Anterior-to-Posterior Tear Repair: CT Arthrographic Features and Correlation with Clinical Outcome. AB - PURPOSE: To evaluate the presence of a superior labral cleft at postoperative computed tomographic (CT) arthrography after superior labral anterior-to posterior lesion (SLAP) repair and to correlate CT arthrographic appearance with clinical outcomes. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. Fifty-six patients who underwent CT arthrography after arthroscopic SLAP repair were included. Two musculoskeletal radiologists retrospectively reviewed CT arthrographic images for the presence, size, location, direction, and shape of a superior labral cleft, which was defined as a detectable contrast material filled focal discontinuity of the labrum within anchor fixation sites of the glenoid. In addition, the glenoid osteolysis ratio was calculated on the basis of the CT arthrographic images. Clinical outcome was evaluated with use of the American Shoulder and Elbow Surgeons (ASES) scoring system. Continuous variables, such as patient age, interval between imaging and surgery, ASES score, and osteolysis ratio, were compared by using the Mann-Whitney U test. RESULTS: A superior labral cleft was observed in 27 of the 56 patients (48%). The mean width and depth of the superior labral clefts was 2.1 mm +/- 1.1 and 2.8 mm +/- 0.8, respectively. The superior labral clefts extended posterior to the biceps anchor in 16 of the 27 patients (59%), were curved medially in 24 (89%), and had a smooth margin in 22 (81%). No significant association was observed between the presence of a superior labral cleft and the ASES score (P = .805) or patient age (P = .290). Superior labral clefts were observed more commonly in cases with a long interval since surgery (P = .007) and a high osteolysis ratio (P = .011). CONCLUSION: Superior labral clefts are frequently observed on CT arthrographic images after arthroscopic SLAP repair and do not correlate with clinical outcome. PMID- 26131914 TI - The Effectiveness and Safety of Antipsychotic and Antidepressant Medications in Individuals with 22q11.2 Deletion Syndrome. AB - OBJECTIVE: The purpose of this study was to evaluate the effectiveness and safety of antipsychotic and antidepressant medications in individuals with 22q11.2 deletion syndrome (22q11.2 DS) and psychiatric comorbidity. METHODS: We used a record review, structured clinical interviews, and the Clinical Global Impressions (CGI) scale to retrospectively assess the effectiveness and safety of antipsychotic medications for schizophrenia spectrum disorders and of antidepressant medications for depressive and anxiety disorders in 40 individuals with 22q11.2DS. RESULTS: We observed significant improvement in CGI-Severity scores in individuals with 22q11.2DS treated with antipsychotic or antidepressant medications, and a ~50% response rate based on the CGI-Improvement score. Adverse events were similar in types and rates to those reported in non-22q11.2 individuals treated with antipsychotics or antidepressants. CONCLUSIONS: Our data show that treatment with antipsychotics and antidepressants may be effective while being relatively safe in individuals with 22q11.2DS. Antipsychotic and antidepressant medications should be considered in any individual with 22q11.2DS who has a psychiatric morbidity, such as psychosis or mood or anxiety disorders. Although the psychotropic medications were generally well tolerated in our sample, more rigorous metabolic and cardiovascular measures are required in future studies to conclusively verify the safety of these medications. PMID- 26131913 TI - Comparison of Existing Response Criteria in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using a 3D Quantitative Approach. AB - PURPOSE: To compare currently available non-three-dimensional methods (Response Evaluation Criteria in Solid Tumors [RECIST], European Association for Study of the Liver [EASL], modified RECIST [mRECIST[) with three-dimensional (3D) quantitative methods of the index tumor as early response markers in predicting patient survival after initial transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: This was a retrospective single-institution HIPAA compliant and institutional review board-approved study. From November 2001 to November 2008, 491 consecutive patients underwent intraarterial therapy for liver cancer with either conventional TACE or TACE with drug-eluting beads. A diagnosis of hepatocellular carcinoma (HCC) was made in 290 of these patients. The response of the index tumor on pre- and post-TACE magnetic resonance images was assessed retrospectively in 78 treatment-naive patients with HCC (63 male; mean age, 63 years +/- 11 [standard deviation]). Each response assessment method (RECIST, mRECIST, EASL, and 3D methods of volumetric RECIST [vRECIST] and quantitative EASL [qEASL]) was used to classify patients as responders or nonresponders by following standard guidelines for the uni- and bidimensional measurements and by using the formula for a sphere for the 3D measurements. The Kaplan-Meier method with the log-rank test was performed for each method to evaluate its ability to help predict survival of responders and nonresponders. Uni- and multivariate Cox proportional hazard ratio models were used to identify covariates that had significant association with survival. RESULTS: The uni- and bidimensional measurements of RECIST (hazard ratio, 0.6; 95% confidence interval [CI]: 0.3, 1.0; P = .09), mRECIST (hazard ratio, 0.6; 95% CI: 0.6, 1.0; P = .05), and EASL (hazard ratio, 1.1; 95% CI: 0.6, 2.2; P = .75) did not show a significant difference in survival between responders and nonresponders, whereas vRECIST (hazard ratio, 0.6; 95% CI: 0.3, 1.0; P = .04), qEASL (Vol) (hazard ratio, 0.5; 95% CI: 0.3, 0.9; P = .02), and qEASL (%) (hazard ratio, 0.3; 95% CI: 0.15, 0.60; P < .001) did show a significant difference between these groups. CONCLUSION: The 3D-based imaging biomarkers qEASL and vRECIST were tumor response criteria that could be used to predict patient survival early after initial TACE and enabled clear identification of nonresponders. PMID- 26131915 TI - Testing the disgust conditioning theory of food-avoidance in adolescents with recent onset anorexia nervosa. AB - Anorexia nervosa is characterized by chronic food avoidance that is resistant to change. Disgust conditioning offers one potential unexplored mechanism for explaining this behavioral disturbance because of its specific role in facilitating food avoidance in adaptive situations. A food based reversal learning paradigm was used to study response flexibility in 14 adolescent females with restricting subtype anorexia nervosa (AN-R) and 15 healthy control (HC) participants. Expectancy ratings were coded as a behavioral measure of flexibility and electromyography recordings from the levator labii (disgust), zygomaticus major (pleasure), and corrugator (general negative affect) provided psychophysiological measures of emotion. Response inflexibility was higher for participants with AN-R, as evidenced by lower extinction and updated expectancy ratings during reversal. EMG responses to food stimuli were predictive of both extinction and new learning. Among AN-R patients, disgust specific responses to food were associated with impaired extinction, as were elevated pleasure responses to the cued absence of food. Disgust conditioning appears to influence food learning in acutely ill patients with AN-R and may be maintained by counter regulatory acquisition of a pleasure response to food avoidance and an aversive response to food presence. Developing strategies to target disgust may improve existing interventions for patients with AN. PMID- 26131916 TI - Reassessment of Melittis melissophyllum L. subsp. melissophyllum iridoidic fraction. AB - The analysis of the polar fraction of Melittis melissophyllum L. subsp. melissophyllum led to the identification of several iridoid glycosides: monomelittoside (1), melittoside (2), harpagide (3), acetyl-harpagide (4) and ajugoside (5). Compounds 3 and 4 are considered marker compounds for the genus and, as well as compounds 1, 2 and 5, were already evidenced in a previous study on the nominal species. It was noteworthy of the presence of allobetonicoside (6) which was never reported for this genus. The isolation of 6 is very relevant because of its allose residue on the structure. Allose has been often found in the species of the subfamily Lamioideae even if it mostly regarded flavonoids considered of chemotaxonomical relevance for some correlated genera of Lamiaceae. Same as allosyl-glycosidic flavonoids, the presence of allosyl-glycosidic iridoids may also be an additional chemosystematic evidence of botanical relationships among Lamiaceae species and genera. PMID- 26131918 TI - Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration. AB - The purpose of this investigation was to determine through the use of fluoxetine the effect of administering a serotonin reuptake inhibitor over several days on the antinociceptive action of MU-morphine type opioid receptor agonist. Investigations were performed on rats of both sexes, both the WKY normotensive strains as well as on the SHR genetically conditioned hypertensive strains. Results showed that the efficacy of morphine analgesia is higher in the SHR strain compared to normotensive rats (WKY). Surprisingly, repeated administration of fluoxetine reduced morphine analgesia, with the weakening of opioid antinociceptive action comparable to the duration of serotonin reuptake inhibitor administration. It was also concluded that the antinociceptive action of morphine in female rats and the alteration of its efficacy as a result of fluoxetine premedication for several days depend on oestrus cycle phase. The highest sensitivity of female rats to morphine was reported in the dioestrus and oestrus phases; much lower values were reported for the metoestrus phase. PMID- 26131919 TI - Delivering opioid maintenance treatment in rural and remote settings. AB - OBJECTIVE: This study explored the delivery of opioid maintenance treatment (OMT) from a specialist program in rural and remote New South Wales (NSW), focusing on the viability of the model and strategies for its improvement. DESIGN: Program evaluation examining configuration and delivery, client characteristics and trends in demand, using policy documents, service data and stakeholder consultations (n = 28). SETTING: The Greater Western Area Health Service, a sparsely populated and large geographic area in NSW. RESULTS: There were four service hubs or primary sites. Three sites were co-located with hospitals and one within community health, with all sites providing assessment, prescribing, dispensing and limited case management. Staff were mainly trained nurses, while prescribers were visiting specialists or sessional GPs. There was minimal OMT provision by community prescribers and dispensers. In 2009, there were 638 clients. They were younger on average than those in OMT across Australia. The most common principal drug of concern was heroin (37-85% of clients), while around one-fifth of clients identified prescription opioids (18-23%). There was a substantial increase in OMT provision between 2006 and 2009 at three program sites. Staff at the sites had limited capacity to engage primary health services and thus reduce their client load. CONCLUSIONS: Findings indicate the need to adjust funding to account for increased demand for OMT and to establish a financial incentive for GP prescribers. Dedicated resourcing is needed for a capacity building role to support the uptake of prescribing and dispensing in community services. PMID- 26131920 TI - Predicting the Parturition Date in Bitches of Different Body Weight by Ultrasonographic Measurements of Inner Chorionic Cavity Diameter and Biparietal Diameter. AB - Predicting the parturition date in dogs by taking ultrasonographic foetometry has opened interesting research areas of veterinary obstetrics. Recently developed calculation formulas of inner chorionic cavity diameter (ICC) and biparietal diameter (BP) are formulas by Luvoni and Grioni (2000). This study is one of the first reports referring to ICC and BP with the use of Luvoni and Grioni formulas for predicting the parturition time in dogs of different body weight in clinical practice conditions. The research material consists of 70 clinically healthy pregnant bitches of 27 breeds and cross-breeds. Bitches were divided into 4 groups according to their body weight. In each of the bitches, ultrasonographic examination of pregnancy was performed at least twice (ICC and BP measurements). Parturition dates for dogs with a body weight over 25 kg were calculated based on formulas intended for the group of medium dogs. It was caused by the lack of appropriate formulas for these groups of dogs. The predicting parturition dates were compared with the actual dates of delivery provided by the bitch owners. Generally, the results obtained in this study are very encouraging and similar or even better than those published by other authors using foetometric measurements. In our research, when comparing the effectiveness of predicting the delivery date based on foetometric formulas by Luvoni and Grioni (2000), it was proved that in all groups of dogs, even those over 25 kg, ICC and BP measurements at both accuracy levels were characterized similar reliability. PMID- 26131921 TI - Effects of Light and Salinity Stresses in Production of Mycosporine-Like Amino Acids by Gymnodinium catenatum (Dinophyceae). AB - Mycosporine-like amino acids (MAAs) were analyzed in a Portuguese Gymnodinium catenatum strain when transferred to high salinity and high light conditions. Total MAA concentrations increased progressively between 30 and 36 psu, attaining at 36 psu 2.9-fold the 30 psu treatment. When abruptly transferred to solar light in an outdoor shadowed location, MAA concentration increased steadily along the day for most compounds. After 8 h, mycosporine-glycine, palythene and M-319 attained or surpassed 25-fold their initial concentration, while M-370 only attained 4-fold concentration. When transferred from halogen to fluorescent light, polar MAAs such as shinorine and porphyra-334, increased until day two and then declined, while M-370 increase slowly, becoming the dominant compound from the profile after 1 week. These experiments put into evidence the relation of palythene with M-319, which was further identified as its acid degradation product, palythine. Acid degradation of M-370 originated M-324, while M-311 seems to be the precursor of M-370. Under high salinity and high light conditions chain formation was altered toward shorter chains or solitary cells. This alteration can represent a morphological stress sign, which in the natural environment could affect average population speed during daily vertical migrations. PMID- 26131922 TI - Detection of Axonally Localized mRNAs in Brain Sections Using High-Resolution In Situ Hybridization. AB - mRNAs are frequently localized to vertebrate axons and their local translation is required for axon pathfinding or branching during development and for maintenance, repair or neurodegeneration in postdevelopmental periods. High throughput analyses have recently revealed that axons have a more dynamic and complex transcriptome than previously expected. These analysis, however have been mostly done in cultured neurons where axons can be isolated from the somato dendritic compartments. It is virtually impossible to achieve such isolation in whole tissues in vivo. Thus, in order to verify the recruitment of mRNAs and their functional relevance in a whole animal, transcriptome analyses should ideally be combined with techniques that allow the visualization of mRNAs in situ. Recently, novel ISH technologies that detect RNAs at a single-molecule level have been developed. This is especially important when analyzing the subcellular localization of mRNA, since localized RNAs are typically found at low levels. Here we describe two protocols for the detection of axonally-localized mRNAs using a novel ultrasensitive RNA ISH technology. We have combined RNAscope ISH with axonal counterstain using fluorescence immunohistochemistry or histological dyes to verify the recruitment of Atf4 mRNA to axons in vivo in the mature mouse and human brains. PMID- 26131923 TI - Endoscopic approaches to gastroparesis. AB - PURPOSE OF REVIEW: This review covers the cause, evaluation and treatment options for gastroparesis. Symptoms of delayed gastric emptying are increasingly seen by gastroenterologists and gastrointestinal surgeons. Endoscopy - both laparoscopic and flexible - is increasingly important in treatment algorithms for this problem. RECENT FINDINGS: Gastroparesis is increasingly being seen in clinical practice. A progressive algorithm needs to be followed in these challenging cases: starting with medical treatment and diet modification, progressing through endoscopic treatments including new ones such as per-oral pyloromyotomy, and finally laparoscopic treatments including gastrectomy. SUMMARY: Endoscopic interventions are effective treatments for certain gastroparesis patients. New procedures offer a minimally invasive alternative to more radical options and should probably be more widely adopted. PMID- 26131924 TI - Differential thermosensitivity in mixed syndrome cardiac sodium channel mutants. AB - Cardiac arrhythmias are often associated with mutations in SCN5A the gene that encodes the cardiac paralogue of the voltage-gated sodium channel, NaV 1.5. The NaV 1.5 mutants R1193Q and E1784K give rise to both long QT and Brugada syndromes. Various environmental factors, including temperature, may unmask arrhythmia. We sought to determine whether temperature might be an arrhythmogenic trigger in these two mixed syndrome mutants. Whole-cell patch clamp was used to measure the biophysical properties of NaV 1.5 WT, E1784K and R1193Q mutants. Recordings were performed using Chinese hamster ovary (CHOk1) cells transiently transfected with the NaV 1.5 alpha subunit (WT, E1784K, or R1193Q), beta1 subunit, and eGFP. The channels' voltage-dependent and kinetic properties were measured at three different temperatures: 10oC, 22oC, and 34oC. The E1784K mutant is more thermosensitive than either WT or R1193Q channels. When temperature is elevated from 22 degrees C to 34 degrees C, there is a greater increase in late INa and use-dependent inactivation in E1784K than in WT or R1193Q. However, when temperature is lowered to 10 degrees C, the two mutants show a decrease in channel availability. Action potential modelling using Q10 fit values, extrapolated to physiological and febrile temperatures, show a larger transmural voltage gradient in E1784K compared to R1193Q and WT with hyperthermia. The E1784K mutant is more thermosensitive than WT or R1193Q channels. This enhanced thermosensitivity may be a mechanism for arrhythmogenesis in patients with E1784K sodium channels. PMID- 26131926 TI - Hierarchical Core/Shell NiCo2O4@NiCo2O4 Nanocactus Arrays with Dual functionalities for High Performance Supercapacitors and Li-ion Batteries. AB - We report the synthesis of three dimensional (3D) NiCo2O4@NiCo2O4 nanocactus arrays grown directly on a Ni current collector using a facile solution method followed by electrodeposition. They possess a unique 3D hierarchical core-shell structure with large surface area and dual-functionalities that can serve as electrodes for both supercapacitors (SCs) and lithium-ion batteries (LIBs). As the SC electrode, they deliver a remarkable specific capacitance of 1264 F g(-1) at a current density of 2 A g(-1) and ~93.4% of capacitance retention after 5000 cycles at 2 A g(-1). When used as the anode for LIBs, a high reversible capacity of 925 mA h g(-1) is achieved at a rate of 120 mA g(-1) with excellent cyclic stability and rate capability. The ameliorating features of the NiCo2O4 core/shell structure grown directly on highly conductive Ni foam, such as hierarchical mesopores, numerous hairy needles and a large surface area, are responsible for the fast electron/ion transfer and large active sites which commonly contribute to the excellent electrochemical performance of both the SC and LIB electrodes. PMID- 26131927 TI - Spontaneous Recurrence of Deposition and Dissolution of a Solid Layer on a Solution Surface. AB - We investigated the spontaneous recurrence of deposition and dissolution of camphor layer on the surface of camphor methanol solution. This recurrence is a novel rhythmic process concerned with solid-liquid phase transition. To elucidate the underlying mechanism, we measured the solution temperature at different times, and found that the temperature increased and decreased repetitively, correlating with the camphor layer's deposition and dissolution. These experimental results show that the solution temperature plays an important role in recurrence of deposition and dissolution. PMID- 26131925 TI - Identification of vacuoles containing extraintestinal differentiated forms of Legionella pneumophila in colonized Caenorhabditis elegans soil nematodes. AB - Legionella pneumophila, a causative agent of Legionnaires' disease, is a facultative intracellular parasite of freshwater protozoa. Legionella pneumophila features a unique developmental network that involves several developmental forms including the infectious cyst forms. Reservoirs of L. pneumophila include natural and man-made freshwater systems; however, recent studies have shown that isolates of L. pneumophila can also be obtained directly from garden potting soil suggesting the presence of an additional reservoir. A previous study employing the metazoan Caenorhabditis elegans, a member of the Rhabditidae family of free living soil nematodes, demonstrated that the intestinal lumen can be colonized with L. pneumophila. While both replicative forms and differentiated forms were observed in C. elegans, these morphologically distinct forms were initially observed to be restricted to the intestinal lumen. Using live DIC imaging coupled with focused transmission electron microscopy analyses, we report here that L. pneumophila is able to invade and establish Legionella-containing vacuoles (LCVs) in the intestinal cells. In addition, LCVs containing replicative and differentiated cyst forms were observed in the pseudocoelomic cavity and gonadal tissue of nematodes colonized with L. pneumophila. Furthermore, establishment of LCVs in the gonadal tissue was Dot/Icm dependent and required the presence of the endocytic factor RME-1 to gain access to maturing oocytes. Our findings are novel as this is the first report, to our knowledge, of extraintestinal LCVs containing L. pneumophila cyst forms in C. elegans tissues, highlighting the potential of soil-dwelling nematodes as an alternate environmental reservoir for L. pneumophila. PMID- 26131928 TI - Exploring the Effects of Atmospheric Forcings on Evaporation: Experimental Integration of the Atmospheric Boundary Layer and Shallow Subsurface. AB - Evaporation is directly influenced by the interactions between the atmosphere, land surface and soil subsurface. This work aims to experimentally study evaporation under various surface boundary conditions to improve our current understanding and characterization of this multiphase phenomenon as well as to validate numerical heat and mass transfer theories that couple Navier-Stokes flow in the atmosphere and Darcian flow in the porous media. Experimental data were collected using a unique soil tank apparatus interfaced with a small climate controlled wind tunnel. The experimental apparatus was instrumented with a suite of state of the art sensor technologies for the continuous and autonomous collection of soil moisture, soil thermal properties, soil and air temperature, relative humidity, and wind speed. This experimental apparatus can be used to generate data under well controlled boundary conditions, allowing for better control and gathering of accurate data at scales of interest not feasible in the field. Induced airflow at several distinct wind speeds over the soil surface resulted in unique behavior of heat and mass transfer during the different evaporative stages. PMID- 26131929 TI - Nanotubes mediate niche-stem-cell signalling in the Drosophila testis. AB - Stem cell niches provide resident stem cells with signals that specify their identity. Niche signals act over a short range such that only stem cells but not their differentiating progeny receive the self-renewing signals. However, the cellular mechanisms that limit niche signalling to stem cells remain poorly understood. Here we show that the Drosophila male germline stem cells form previously unrecognized structures, microtubule-based nanotubes, which extend into the hub, a major niche component. Microtubule-based nanotubes are observed specifically within germline stem cell populations, and require intraflagellar transport proteins for their formation. The bone morphogenetic protein (BMP) receptor Tkv localizes to microtubule-based nanotubes. Perturbation of microtubule-based nanotubes compromises activation of Dpp signalling within germline stem cells, leading to germline stem cell loss. Moreover, Dpp ligand and Tkv receptor interaction is necessary and sufficient for microtubule-based nanotube formation. We propose that microtubule-based nanotubes provide a novel mechanism for selective receptor-ligand interaction, contributing to the short range nature of niche-stem-cell signalling. PMID- 26131931 TI - Influence maximization in complex networks through optimal percolation. AB - The whole frame of interconnections in complex networks hinges on a specific set of structural nodes, much smaller than the total size, which, if activated, would cause the spread of information to the whole network, or, if immunized, would prevent the diffusion of a large scale epidemic. Localizing this optimal, that is, minimal, set of structural nodes, called influencers, is one of the most important problems in network science. Despite the vast use of heuristic strategies to identify influential spreaders, the problem remains unsolved. Here we map the problem onto optimal percolation in random networks to identify the minimal set of influencers, which arises by minimizing the energy of a many-body system, where the form of the interactions is fixed by the non-backtracking matrix of the network. Big data analyses reveal that the set of optimal influencers is much smaller than the one predicted by previous heuristic centralities. Remarkably, a large number of previously neglected weakly connected nodes emerges among the optimal influencers. These are topologically tagged as low-degree nodes surrounded by hierarchical coronas of hubs, and are uncovered only through the optimal collective interplay of all the influencers in the network. The present theoretical framework may hold a larger degree of universality, being applicable to other hard optimization problems exhibiting a continuous transition from a known phase. PMID- 26131932 TI - Myeloid disease: Another action of a thalidomide derivative. PMID- 26131934 TI - Protistology: How to build a microbial eye. PMID- 26131933 TI - Viral-genetic tracing of the input-output organization of a central noradrenaline circuit. AB - Deciphering how neural circuits are anatomically organized with regard to input and output is instrumental in understanding how the brain processes information. For example, locus coeruleus noradrenaline (also known as norepinephrine) (LC-NE) neurons receive input from and send output to broad regions of the brain and spinal cord, and regulate diverse functions including arousal, attention, mood and sensory gating. However, it is unclear how LC-NE neurons divide up their brain-wide projection patterns and whether different LC-NE neurons receive differential input. Here we developed a set of viral-genetic tools to quantitatively analyse the input-output relationship of neural circuits, and applied these tools to dissect the LC-NE circuit in mice. Rabies-virus-based input mapping indicated that LC-NE neurons receive convergent synaptic input from many regions previously identified as sending axons to the locus coeruleus, as well as from newly identified presynaptic partners, including cerebellar Purkinje cells. The 'tracing the relationship between input and output' method (or TRIO method) enables trans-synaptic input tracing from specific subsets of neurons based on their projection and cell type. We found that LC-NE neurons projecting to diverse output regions receive mostly similar input. Projection-based viral labelling revealed that LC-NE neurons projecting to one output region also project to all brain regions we examined. Thus, the LC-NE circuit overall integrates information from, and broadcasts to, many brain regions, consistent with its primary role in regulating brain states. At the same time, we uncovered several levels of specificity in certain LC-NE sub-circuits. These tools for mapping output architecture and input-output relationship are applicable to other neuronal circuits and organisms. More broadly, our viral-genetic approaches provide an efficient intersectional means to target neuronal populations based on cell type and projection pattern. PMID- 26131935 TI - Eye-like ocelloids are built from different endosymbiotically acquired components. AB - Multicellularity is often considered a prerequisite for morphological complexity, as seen in the camera-type eyes found in several groups of animals. A notable exception exists in single-celled eukaryotes called dinoflagellates, some of which have an eye-like 'ocelloid' consisting of subcellular analogues to a cornea, lens, iris, and retina. These planktonic cells are uncultivated and rarely encountered in environmental samples, obscuring the function and evolutionary origin of the ocelloid. Here we show, using a combination of electron microscopy, tomography, isolated-organelle genomics, and single-cell genomics, that ocelloids are built from pre-existing organelles, including a cornea-like layer made of mitochondria and a retinal body made of anastomosing plastids. We find that the retinal body forms the central core of a network of peridinin-type plastids, which in dinoflagellates and their relatives originated through an ancient endosymbiosis with a red alga. As such, the ocelloid is a chimaeric structure, incorporating organelles with different endosymbiotic histories. The anatomical complexity of single-celled organisms may be limited by the components available for differentiation, but the ocelloid shows that pre existing organelles can be assembled into a structure so complex that it was initially mistaken for a multicellular eye. Although mitochondria and plastids are acknowledged chiefly for their metabolic roles, they can also be building blocks for greater structural complexity. PMID- 26131936 TI - Developmental biology: Nanotubes in the niche. PMID- 26131938 TI - Corrigendum: Greenland supraglacial lake drainages triggered by hydrologically induced basal slip. PMID- 26131939 TI - Acantholytic Dyskeratotic Epidermal Nevus. PMID- 26131937 TI - Lenalidomide induces ubiquitination and degradation of CK1alpha in del(5q) MDS. AB - Lenalidomide is a highly effective treatment for myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)). Here, we demonstrate that lenalidomide induces the ubiquitination of casein kinase 1A1 (CK1alpha) by the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)), resulting in CK1alpha degradation. CK1alpha is encoded by a gene within the common deleted region for del(5q) MDS and haploinsufficient expression sensitizes cells to lenalidomide therapy, providing a mechanistic basis for the therapeutic window of lenalidomide in del(5q) MDS. We found that mouse cells are resistant to lenalidomide but that changing a single amino acid in mouse Crbn to the corresponding human residue enables lenalidomide-dependent degradation of CK1alpha. We further demonstrate that minor side chain modifications in thalidomide and a novel analogue, CC-122, can modulate the spectrum of substrates targeted by CRL4(CRBN). These findings have implications for the clinical activity of lenalidomide and related compounds, and demonstrate the therapeutic potential of novel modulators of E3 ubiquitin ligases. PMID- 26131940 TI - CMS Encourages Physicians to Access User Accounts Prior to Computer System Update. PMID- 26131941 TI - Role of the Family Physician in the Management of Cystic Fibrosis. PMID- 26131943 TI - Diagnosis and Management of Hepatitis C. AB - Hepatitis C virus (HCV) infection, a major cause of chronic liver disease and cirrhosis, is predominantly transmitted by exposure to blood or body fluids. The infection progresses to a chronic state in 80% of patients, whereas the virus clears completely after the acute infection in 20% of patients. Screening for HCV with an anti-HCV antibody test is recommended for all adults at high risk of infection, and one-time screening is recommended in adults born between 1945 and 1965. If the anti-HCV antibody test result is positive, current infection should be confirmed with a qualitative HCV RNA test. In patients with confirmed HCV infection, quantitative HCV RNA testing and testing for HCV genotype is recommended. An assessment of the degree of liver fibrosis with liver biopsy or noninvasive testing is necessary to determine the urgency of treatment. Treatment of patients with chronic HCV infection should be considered based on genotype, extent of fibrosis or cirrhosis, prior treatment, comorbidities, and potential adverse effects. The goal of therapy is to reduce all-cause mortality and liver associated complications. Although interferon-based regimens have been the mainstay of treatment for HCV infection, the U.S. Food and Drug Administration recently approved two combination-pill interferon-free treatments (ledipasvir plus sofosbuvir, and ombitasvir/paritaprevir/ritonavir plus dasabuvir) for chronic HCV genotype 1. PMID- 26131944 TI - Preventive Health Care for Men Who Have Sex with Men. AB - Men who have sex with men (MSM) comprise at least 4% of males in the United States. MSM may describe themselves as gay, bisexual, or heterosexual. Because current medical practice does not always facilitate discussion of sexual behaviors, this group of men may face barriers to receiving culturally competent, comprehensive health care, including preventive services. Barriers include a lack of a welcoming clinical environment, lack of adequate health insurance, and sexual minority stress. Health issues that have a disproportionate impact on MSM include mental health and behavioral problems, smoking and illicit substance use, and sexually transmitted infections (STIs). Family physicians must be prepared to ask explicit questions about sexual activities to determine risk levels for STIs. MSM should receive the same immunizations routinely recommended for other patients, as well as for hepatitis A and B viruses. Although anal Papanicolaou testing is available to screen for cytologic abnormalities, there are no consistent guidelines about its effectiveness. Preexposure prophylaxis is an option for MSM who are at very high risk of human immunodeficiency virus (HIV) infection. For MSM who are not taking preexposure prophylaxis and report a recent high-risk exposure to HIV, postexposure prophylaxis should be offered immediately, preferably within 72 hours of exposure. Because STIs are commonly asymptomatic, screening should be based on risk rather than symptoms. Screening for hepatitis C virus infection is recommended for HIV-positive MSM at least annually and more often for high-risk individuals. PMID- 26131945 TI - Recognition and Differential Diagnosis of Psychosis in Primary Care. AB - Psychosis is a symptom complex that may include hallucinations, delusions, disorders of thought, and disorganized speech or behavior. Acute psychosis is primary if it is symptomatic of a psychiatric disorder, or secondary if caused by a specific medical condition. Patients with primary psychiatric disorders are likely to have auditory hallucinations, prominent cognitive disorders, and complicated delusions. If psychosis is caused by a medical condition, the patient may exhibit cognitive changes and abnormal vital signs, and may have visual hallucinations. Illicit drug use is the most common medical cause of acute psychosis. Clinicians should ask about recent head injury or trauma, seizures, cerebrovascular disease, or new or worsening headaches. A subacute onset of psychosis should raise suspicion for an oncologic cause. Collateral history from family members is helpful in establishing the presentation and course of the illness. The physical examination should include complete neurologic and mental status assessments. Tachycardia or severe hypertension may indicate drug toxicity or thyrotoxicosis; fever may suggest encephalitis or porphyria. Suggested initial laboratory tests include a complete blood count, metabolic profile, thyroid function tests, urine toxicology, and measurement of parathyroid hormone, calcium, vitamin B12, folate, and niacin. Testing for human immunodeficiency virus infection and syphilis should also be considered. Prompt recognition of the etiology of psychosis may improve treatment, consultation, and prognosis. PMID- 26131946 TI - Primary Care Behavioral Interventions to Reduce Illicit Drug and Nonmedical Pharmaceutical Use in Children. PMID- 26131947 TI - Skin-Colored, Dome-Shaped Papule on the Upper Lip. PMID- 26131930 TI - Directional dominance on stature and cognition in diverse human populations. AB - Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 * 10(-300), 2.1 * 10(-6), 2.5 * 10(-10) and 1.8 * 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been. PMID- 26131952 TI - Hepatitis C. PMID- 26131953 TI - Men Who Have Sex with Men. PMID- 26131954 TI - Catalytic Dual 1,1-H-Abstraction/Insertion for Domino Spirocyclizations. AB - A catalytic domino spirocyclization of 1,7-enynes with simple cycloalkanes and cyclo-1,3-dicarbonyls has been established via multiple C-C bond formations from alkynyl/alkenyl functions and dual alpha,alpha-C(sp(3))-H abstraction/insertion. The reaction involves addition, 6-exo-dig cyclization and radical coupling sequences under convenient catalytic conditions and provides a concise access to spiro cyclopenta[c]quinolines in good to excellent yields. PMID- 26131955 TI - Comment on: Long-Term Renal Function in Unilateral Non-Syndromic Renal Tumor Survivors Treated According to International Society of Pediatric Oncology Protocols. PMID- 26131956 TI - The Subcellular Localisation of the Human Papillomavirus (HPV) 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers. AB - Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV "early" genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2) selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa) through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention. PMID- 26131957 TI - Viroporins, Examples of the Two-Stage Membrane Protein Folding Model. AB - Viroporins are small, alpha-helical, hydrophobic virus encoded proteins, engineered to form homo-oligomeric hydrophilic pores in the host membrane. Viroporins participate in multiple steps of the viral life cycle, from entry to budding. As any other membrane protein, viroporins have to find the way to bury their hydrophobic regions into the lipid bilayer. Once within the membrane, the hydrophobic helices of viroporins interact with each other to form higher ordered structures required to correctly perform their porating activities. This two-step process resembles the two-stage model proposed for membrane protein folding by Engelman and Poppot. In this review we use the membrane protein folding model as a leading thread to analyze the mechanism and forces behind the membrane insertion and folding of viroporins. We start by describing the transmembrane segment architecture of viroporins, including the number and sequence characteristics of their membrane-spanning domains. Next, we connect the differences found among viroporin families to their viral genome organization, and finalize focusing on the pathways used by viroporins in their way to the membrane and on the transmembrane helix-helix interactions required to achieve proper folding and assembly. PMID- 26131958 TI - Pan-Genome Analysis of Brazilian Lineage A Amoebal Mimiviruses. AB - Since the recent discovery of Samba virus, the first representative of the family Mimiviridae from Brazil, prospecting for mimiviruses has been conducted in different environmental conditions in Brazil. Recently, we isolated using Acanthamoeba sp. three new mimiviruses, all of lineage A of amoebal mimiviruses: Kroon virus from urban lake water; Amazonia virus from the Brazilian Amazon river; and Oyster virus from farmed oysters. The aims of this work were to sequence and analyze the genome of these new Brazilian mimiviruses (mimi-BR) and update the analysis of the Samba virus genome. The genomes of Samba virus, Amazonia virus and Oyster virus were 97%-99% similar, whereas Kroon virus had a low similarity (90%-91%) with other mimi-BR. A total of 3877 proteins encoded by mimi-BR were grouped into 974 orthologous clusters. In addition, we identified three new ORFans in the Kroon virus genome. Additional work is needed to expand our knowledge of the diversity of mimiviruses from Brazil, including if and why among amoebal mimiviruses those of lineage A predominate in the Brazilian environment. PMID- 26131959 TI - Less Grease, Please. Phosphatidylethanolamine Is the Only Lipid Required for Replication of a (+)RNA Virus. AB - All positive strand RNA viruses of eukaryotes replicate their genomes in association with membranes. These viruses actively change cellular lipid metabolism to build replication membranes enriched in specific lipids. The ubiquitous use of membranes by positive strand RNA viruses apparently holds major evolutionary advantages; however our understanding of the mechanistic role of membranes, let alone of specific lipid components of the membrane bilayer, in the viral replication cycle is minimal. The replication complexes that can be isolated from infected cells, or reconstituted in vitro from crude cell lysates, do not allow controlled manipulation of the membrane constituents thus limiting their usefulness for understanding how exactly membranes support the replication reaction. Recent work from Peter Nagy group demonstrates that replication of a model positive strand RNA virus can be reconstituted in the in vitro reaction with liposomes of chemically defined composition and reveals an exclusive role of phosphatidylethanolamine in sustaining efficient viral RNA replication. This study opens new possibilities for investigation of membrane contribution in the replication process that may ultimately lead to development of novel broad spectrum antiviral compounds targeting the membrane-dependent elements of the replication cycle conserved among diverse groups of viruses. PMID- 26131962 TI - The impact of early growth patterns and infant feeding on body composition at 3 years of age. AB - Early excessive weight gain is positively associated with later obesity, and yet the effect of weight gain during specific periods and the impact of infant feeding practices are debated. The objective of the present study was to examine the impact of weight gain in periods of early childhood on body composition at 3 years, and whether infant feeding modified the relationship between early growth and body composition at 3 years. We studied 233 children from the prospective cohort study, SKOT (in Danish: Smaborns Kost og Trivsel). Birth weight z-scores (BWZ) and change in weight-for-age z-scores (WAZ) from 0 to 5, 5 to 9, 9 to 18 and 18 to 36 months were analysed for relations with body composition (anthropometry and bioelectrical impedance) at 3 years by multivariate regression analysis. BWZ and change in WAZ from 0 to 5 months were positively associated with BMI, fat mass index (FMI) and fat-free mass index (FFMI) at 3 years. Full breastfeeding for 6 months (compared to less than 1 month) eliminated the effect of early growth (P = 0.01). Full breastfeeding for 6 months (compared to less than 1 month) also eliminated the positive relation between BWZ and FMI (P = 0.009). No effect modification of infant feeding was found for FFMI. In conclusion, high birth weight and rapid growth from 0 to 5 months were associated with increased FMI and FFMI at 3 years. Longer duration of full breastfeeding reduced the effect of birth weight and early weight gain on fat mass. PMID- 26131961 TI - Do Pneumococcal Conjugate Vaccines Represent Good Value for Money in a Lower Middle Income Country? A Cost-Utility Analysis in the Philippines. AB - OBJECTIVES: The objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies. METHODS: A cost-utility analysis was conducted. A Markov simulation model was constructed to examine the costs and consequences of PCV10 and PCV13 against the current scenario of no PCV vaccination for a lifetime horizon. A health system perspective was employed to explore different funding schemes, which include universal or partial vaccination coverage subsidized by the government. Results were presented as incremental cost-effectiveness ratios (ICERs) in Philippine peso (Php) per QALY gained (1 USD = 44.20 Php). Probabilistic sensitivity analysis was performed to determine the impact of parameter uncertainty. RESULTS: With universal vaccination at a cost per dose of Php 624 for PCV10 and Php 700 for PCV13, both PCVs are cost-effective compared to no vaccination given the ceiling threshold of Php 120,000 per QALY gained, yielding ICERs of Php 68,182 and Php 54,510 for PCV10 and PCV13, respectively. Partial vaccination of 25% of the birth cohort resulted in significantly higher ICER values (Php 112,640 for PCV10 and Php 84,654 for PCV13) due to loss of herd protection. The budget impact analysis reveals that universal vaccination would cost Php 3.87 billion to 4.34 billion per annual, or 1.6 to 1.8 times the budget of the current national vaccination program. CONCLUSION: The inclusion of PCV in the national immunization program is recommended. PCV13 achieved better value for money compared to PCV10. However, the affordability and sustainability of PCV implementation over the long-term should be considered by decision makers. PMID- 26131960 TI - Structures and Functions of Pestivirus Glycoproteins: Not Simply Surface Matters. AB - Pestiviruses, which include economically important animal pathogens such as bovine viral diarrhea virus and classical swine fever virus, possess three envelope glycoproteins, namely Erns, E1, and E2. This article discusses the structures and functions of these glycoproteins and their effects on viral pathogenicity in cells in culture and in animal hosts. E2 is the most important structural protein as it interacts with cell surface receptors that determine cell tropism and induces neutralizing antibody and cytotoxic T-lymphocyte responses. All three glycoproteins are involved in virus attachment and entry into target cells. E1-E2 heterodimers are essential for viral entry and infectivity. Erns is unique because it possesses intrinsic ribonuclease (RNase) activity that can inhibit the production of type I interferons and assist in the development of persistent infections. These glycoproteins are localized to the virion surface; however, variations in amino acids and antigenic structures, disulfide bond formation, glycosylation, and RNase activity can ultimately affect the virulence of pestiviruses in animals. Along with mutations that are driven by selection pressure, antigenic differences in glycoproteins influence the efficacy of vaccines and determine the appropriateness of the vaccines that are currently being used in the field. PMID- 26131963 TI - Generation of Induced Pluripotent Stem Cells from Frozen Buffy Coats using Non integrating Episomal Plasmids. AB - Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by forcing the expression of four transcription factors (Oct-4, Sox-2, Klf-4, and c Myc), typically expressed by human embryonic stem cells (hESCs). Due to their similarity with hESCs, iPSCs have become an important tool for potential patient specific regenerative medicine, avoiding ethical issues associated with hESCs. In order to obtain cells suitable for clinical application, transgene-free iPSCs need to be generated to avoid transgene reactivation, altered gene expression and misguided differentiation. Moreover, a highly efficient and inexpensive reprogramming method is necessary to derive sufficient iPSCs for therapeutic purposes. Given this need, an efficient non-integrating episomal plasmid approach is the preferable choice for iPSC derivation. Currently the most common cell type used for reprogramming purposes are fibroblasts, the isolation of which requires tissue biopsy, an invasive surgical procedure for the patient. Therefore, human peripheral blood represents the most accessible and least invasive tissue for iPSC generation. In this study, a cost-effective and viral-free protocol using non-integrating episomal plasmids is reported for the generation of iPSCs from human peripheral blood mononuclear cells (PBMNCs) obtained from frozen buffy coats after whole blood centrifugation and without density gradient separation. PMID- 26131964 TI - Highly efficient bioinspired molecular Ru water oxidation catalysts with negatively charged backbone ligands. AB - The oxygen evolving complex (OEC) of the natural photosynthesis system II (PSII) oxidizes water to produce oxygen and reducing equivalents (protons and electrons). The oxygen released from PSII provides the oxygen source of our atmosphere; the reducing equivalents are used to reduce carbon dioxide to organic products, which support almost all organisms on the Earth planet. The first photosynthetic organisms able to split water were proposed to be cyanobacteria like ones appearing ca. 2.5 billion years ago. Since then, nature has chosen a sustainable way by using solar energy to develop itself. Inspired by nature, human beings started to mimic the functions of the natural photosynthesis system and proposed the concept of artificial photosynthesis (AP) with the view to creating energy-sustainable societies and reducing the impact on the Earth environments. Water oxidation is a highly energy demanding reaction and essential to produce reducing equivalents for fuel production, and thereby effective water oxidation catalysts (WOCs) are required to catalyze water oxidation and reduce the energy loss. X-ray crystallographic studies on PSII have revealed that the OEC consists of a Mn4CaO5 cluster surrounded by oxygen rich ligands, such as oxyl, oxo, and carboxylate ligands. These negatively charged, oxygen rich ligands strongly stabilize the high valent states of the Mn cluster and play vital roles in effective water oxidation catalysis with low overpotential. This Account describes our endeavors to design effective Ru WOCs with low overpotential, large turnover number, and high turnover frequency by introducing negatively charged ligands, such as carboxylate. Negatively charged ligands stabilized the high valent states of Ru catalysts, as evidenced by the low oxidation potentials. Meanwhile, the oxygen production rates of our Ru catalysts were improved dramatically as well. Thanks to the strong electron donation ability of carboxylate containing ligands, a seven-coordinate Ru(IV) species was isolated as a reaction intermediate, shedding light on the reaction mechanisms of Ru catalyzed water oxidation chemistry. Auxiliary ligands have dramatic effects on the water oxidation catalysis in terms of the reactivity and the reaction mechanism. For instance, Ru-bda (H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid) water oxidation catalysts catalyze Ce(IV)-driven water oxidation extremely fast via the radical coupling of two Ru(V)?O species, while Ru-pda (H2pda = 1,10 phenanthroline-2,9-dicarboxylic acid) water oxidation catalysts catalyze the same reaction slowly via water nucleophilic attack on a Ru(V)?O species. With a number of active Ru catalysts in hands, light driven water oxidation was accomplished using catalysts with low catalytic onset potentials. The structures of molecular catalysts could be readily tailored to introduce additional functional groups, which favors the fabrication of state-of-the-art Ru-based water oxidation devices, such as electrochemical water oxidation anodes and photo-electrochemical anodes. The development of efficient water oxidation catalysts has led to a step forward in the sustainable energy system. PMID- 26131966 TI - Remission in rheumatoid arthritis: is it all the same? AB - Remission is the key treatment goal in rheumatoid arthritis and should provide the optimal state for patients. Clinical remission criteria are based on composite scores of disease activity and are widely used in clinical practice and trials. With the use of biologic therapies and treat to target strategies, rates of clinical remission have significantly improved. Despite achieving this target, many patients demonstrate structural and functional deterioration. This raises the question regarding the validity of clinical criteria, although they have evolved significantly over the years. Imaging modalities such as ultrasound have been described as more accurate methods of assessing the remission state compared with clinical assessment alone. Furthermore, immuno-pathological assessments are gaining significant interest as this would enable assessment of disease activity at the primary site of pathology. Further research is required to develop accurate biomarkers of remission. We aimed to review the evolution of remission criteria in rheumatoid arthritis to date and to evaluate novel concepts in and the future of defining remission. PMID- 26131967 TI - Recent progress in transition-metal-catalyzed reduction of molecular dinitrogen under ambient reaction conditions. AB - This paper describes our recent progress in catalytic nitrogen fixation by using transition-metal-dinitrogen complexes as catalysts. Two reaction systems for the catalytic transformation of molecular dinitrogen into ammonia and its equivalent such as silylamine under ambient reaction conditions have been achieved by the molybdenum-, iron-, and cobalt-dinitrogen complexes as catalysts. Many new findings presented here may provide new access to the development of economical nitrogen fixation in place of the Haber-Bosch process. PMID- 26131965 TI - Likert score 3 prostate lesions: Association between whole-lesion ADC metrics and pathologic findings at MRI/ultrasound fusion targeted biopsy. AB - BACKGROUND: To assess associations between whole-lesion apparent diffusion coefficient (ADC) metrics and pathologic findings of Likert score 3 prostate lesions at MRI/ultrasound fusion targeted biopsy. METHODS: This retrospective Institutional Review Board-approved study received a waiver of consent. We identified patients receiving a highest lesion score of 3 on 3 Tesla multiparametric MRI reviewed by a single experienced radiologist using a 5-point Likert scale and who underwent fusion biopsy. A total of 188 score 3 lesions in 158 patients were included. Three-dimensional volumes-of-interest encompassing each lesion were traced on ADC maps. Logistic regression was used to predict biopsy results based on whole-lesion ADC metrics and patient biopsy history. Biopsy yield was compared between metrics. RESULTS: By lesion, targeted biopsy identified tumor in 22.3% and Gleason score (GS) > 6 tumor in 8.5%, although results varied by biopsy history: biopsy-naive (n = 80), 20.0%/8.8%; prior negative biopsy (n = 53), 9.4%/1.9%; prior positive biopsy (n = 55): 40.0%/14.5%. Biopsy history, whole-lesion mean ADC, whole-lesion ADC10-25 , and whole-lesion ADC25-50 were each significantly associated with tumor or GS > 6 tumor at fusion biopsy (P <= 0.047). In men without prior negative prostate biopsy, whole-lesion ADC25-50 <= 1.04*10(-3) mm2 /s achieved 90.0% sensitivity and 50.0% specificity for GS > 6 tumor, which was significantly higher (P < 0.001) than specificity of PSA (17.5%) at identical sensitivity. CONCLUSION: For score 3 lesions in patients without prior negative biopsy, whole-lesion ADC metrics help detect GS > 6 cancer while avoiding negative biopsies. However, deferral of fusion biopsy may be considered for score 3 lesions in patients with prior negative biopsy (without applying whole-lesion ADC metrics) given exceedingly low (~ 2%) frequency of GS > 6 tumor in this group. PMID- 26131968 TI - Palladium-Catalyzed Heck-type Domino Cyclization and Carboxylation to Synthesize Carboxylic Acids by Utilizing Chloroform as the Carbon Monoxide Source. AB - A palladium-catalyzed domino cyclization and carboxylation reaction for synthesis of a variety of carboxylic acids was developed, where chloroform was used as "carbon monoxide" source. The in situ generated neopentylpalladium species by Heck cyclization was efficiently trapped by dichlorocarbene to form a series of carboxylic acids. It was found that in this type of domino reaction CHCl3 is a convenient and safe alternation for CO gas. PMID- 26131972 TI - Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1 and MSI2 during Folliculogenesis. AB - Characterizing the mechanisms underlying follicle development in the ovary is crucial to understanding female fertility and is an area of increasing research interest. The RNA binding protein Musashi is essential for post-transcriptional regulation of oocyte maturation in Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized. In this study we determined the expression of mammalian Musashi proteins MSI1 and MSI2 during mouse folliculogenesis, and through the use of a MSI2-specific knockout mouse model we identified that MSI2 is essential for normal follicle development. Time-course characterization of MSI1 and MSI2 revealed distinct differences in steady-state mRNA levels and protein expression/localization at important developmental time-points during folliculogenesis. Using a gene-trap mouse model that inactivates Msi2, we observed a significant decrease in ovarian mass, and change in follicle-stage composition due to developmental blocking of antral stage follicles and pre-antral follicle loss through atresia. We also confirmed that hormonally stimulated Msi2-deficient mice produce significantly fewer MII oocytes (60.9% less than controls, p < 0.05). Furthermore, the majority of these oocytes are of poor viability (62.2% non-viable/apoptotic, p < 0.05), which causes a reduction in female fertility evidenced by decreased litter size in Msi2-deficient animals (33.1% reduction to controls, p < 0.05). Our findings indicate that MSI1 and MSI2 display distinct expression profiles during mammalian folliculogenesis and that MSI2 is required for pre-antral follicle development. PMID- 26131973 TI - Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution. AB - Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (Group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (Groups 2-4) that control a wide variety of adaptive responses such as morphological development and the management of stress. A recurring theme in sigma factor control is their sequestration by anti-sigma factors that occlude their RNAP binding determinants. Sigma factors are then released through a wide variety of mechanisms, often involving branched signal transduction pathways that allow the integration of distinct signals. Three major strategies for sigma release are discussed: regulated proteolysis, partner-switching, and direct sensing by the anti-sigma factor. PMID- 26131974 TI - NF-kappaB Signaling in Chronic Inflammatory Airway Disease. AB - Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments. In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression. The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-kappaB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology. The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF kappaB induced gene transcription. Ligand bound GC receptors (GRs) bind NF-kappaB to suppress the transcription of NF-kappaB responsive genes (i.e., transrepression). However, in severe asthma and COPD, the transrepression of NF kappaB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling. Therapeutics which target NF-kappaB activation, including inhibitors of IkappaB kinases (IKKs) are potential treatments for asthma and COPD. Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-kappaB transrepression. This review examines NF-kappaB signaling in airway inflammation and its potential as target for treatment of asthma and COPD. PMID- 26131975 TI - Study of Protein Phosphatase 2A (PP2A) Activity in LPS-Induced Tolerance Using Fluorescence-Based and Immunoprecipitation-Aided Methodology. AB - Protein phosphatase 2A (PP2A) is one of the most abundant intracellular serine/threonine (Ser/Thr) phosphatases accounting for 1% of the total cellular protein content. PP2A is comprised of a heterodimeric core enzyme and a substrate specific regulatory subunit. Potentially, at least seventy different compositions of PP2A exist because of variable regulatory subunit binding that accounts for various activity modulating numerous cell functions. Due to the constitutive phosphatase activity present inside cells, a sensitive assay is required to detect the changes of PP2A activity under various experimental conditions. We optimized a fluorescence assay (DIFMU assay) by combining it with prior anti-PP2A immunoprecipitation to quantify PP2A-specific phosphatase activity. It is also known that prior exposure to lipopolysaccharides (LPS) induces "immune tolerance" of the cells to subsequent stimulation. Herein we report that PP2A activity is upregulated in tolerized peritoneal macrophages, corresponding to decreased TNF alpha secretion upon second LPS stimulation. We further examined the role of PP2A in the tolerance effect by using PP2ACalphal degrees xl degrees x;lyM-Cre conditional knockout macrophages. We found that PP2A phosphatase activity cannot be further increased by tolerance. TNF-alpha secretion from tolerized PP2ACalphal degrees xl degrees x;lyM-Cre macrophages is higher than tolerized control macrophages. Furthermore, we showed that the increased TNF-alpha secretion may be due to an epigenetic transcriptionally active signature on the promoter of TNF alpha gene rather than regulation of the NFkappaB/IkappaB signaling pathway. These results suggest a role for increased PP2A activity in the regulation of immune tolerance. PMID- 26131976 TI - Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-kappaB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis. AB - Appropriate innate and adaptive immune responses are essential for protection and resolution against chemical, physical or biological insults. Immune cell polarization is fundamental in orchestrating distinct phases of inflammation, specifically acute phase responses followed by resolution and tissue repair. Dysregulation of immune cell and inflammatory responses is a hallmark of multiple diseases encompassing atherosclerosis, rheumatoid arthritis, psoriasis and metabolic syndromes. A master transcriptional mediator of diverse inflammatory signaling and immune cell function is NF-kappaB, and altered control of this key regulator can lead to an effective switch from acute to chronic inflammatory responses. Members of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors crosstalk with NF-kappaB to regulate immune cell function(s). Within the NR superfamily the NR4A1-3 orphan receptors have emerged as important regulators of immune cell polarization and NF-kappaB signaling. NR4A receptors modulate NF-kappaB activity in a dynamic fashion, either repressing or enhancing target gene expression leading to altered inflammatory outcome. Here we will discuss the pivotal role NR4A's receptors play in orchestrating immune cell homeostasis through molecular crosstalk with NF-kappaB. Specifically, we will examine such NR4A/NF-kappaB interactions within the context of distinct cell phenotypes, including monocyte, macrophage, T cells, endothelial, and mesenchymal cells, which play a role in inflammation-associated disease. Finally, we review the therapeutic potential of altering NR4A/NF-kappaB interactions to limit hyper inflammatory responses in vivo. PMID- 26131977 TI - High-Resolution Respirometry for Simultaneous Measurement of Oxygen and Hydrogen Peroxide Fluxes in Permeabilized Cells, Tissue Homogenate and Isolated Mitochondria. AB - Whereas mitochondria are well established as the source of ATP in oxidative phosphorylation (OXPHOS), it is debated if they are also the major cellular sources of reactive oxygen species (ROS). Here we describe the novel approach of combining high-resolution respirometry and fluorometric measurement of hydrogen peroxide (H2O2) production, applied to mitochondrial preparations (permeabilized cells, tissue homogenate, isolated mitochondria). The widely used H2O2 probe Amplex Red inhibited respiration in intact and permeabilized cells and should not be applied at concentrations above 10 uM. H2O2 fluxes were generally less than 1% of oxygen fluxes in physiological substrate and coupling states, specifically in permeabilized cells. H2O2 flux was consistently highest in the Complex II-linked LEAK state, reduced with CI&II-linked convergent electron flow and in mitochondria respiring at OXPHOS capacity, and were further diminished in uncoupled mitochondria respiring at electron transfer system capacity. Simultaneous measurement of mitochondrial respiration and H2O2 flux requires careful optimization of assay conditions and reveals information on mitochondrial function beyond separate analysis of ROS production. PMID- 26131981 TI - The Health Equity and Effectiveness of Policy Options to Reduce Dietary Salt Intake in England: Policy Forecast. AB - BACKGROUND: Public health action to reduce dietary salt intake has driven substantial reductions in coronary heart disease (CHD) over the past decade, but avoidable socio-economic differentials remain. We therefore forecast how further intervention to reduce dietary salt intake might affect the overall level and inequality of CHD mortality. METHODS: We considered English adults, with socio economic circumstances (SEC) stratified by quintiles of the Index of Multiple Deprivation. We used IMPACTSEC, a validated CHD policy model, to link policy implementation to salt intake, systolic blood pressure and CHD mortality. We forecast the effects of mandatory and voluntary product reformulation, nutrition labelling and social marketing (e.g., health promotion, education). To inform our forecasts, we elicited experts' predictions on further policy implementation up to 2020. We then modelled the effects on CHD mortality up to 2025 and simultaneously assessed the socio-economic differentials of effect. RESULTS: Mandatory reformulation might prevent or postpone 4,500 (2,900-6,100) CHD deaths in total, with the effect greater by 500 (300-700) deaths or 85% in the most deprived than in the most affluent. Further voluntary reformulation was predicted to be less effective and inequality-reducing, preventing or postponing 1,500 (200 5,000) CHD deaths in total, with the effect greater by 100 (-100-600) deaths or 49% in the most deprived than in the most affluent. Further social marketing and improvements to labelling might each prevent or postpone 400-500 CHD deaths, but minimally affect inequality. CONCLUSIONS: Mandatory engagement with industry to limit salt in processed-foods appears a promising and inequality-reducing option. For other policy options, our expert-driven forecast warns that future policy implementation might reach more deprived individuals less well, limiting inequality reduction. We therefore encourage planners to prioritise equity. PMID- 26131982 TI - Daytime Physical Activity and Sleep in Hospitalized Older Adults: Association with Demographic Characteristics and Disease Severity. AB - OBJECTIVES: To assess objectively measured daytime physical activity and sleep duration and efficiency in hospitalized older adults and explore associations with demographic characteristics and disease severity. DESIGN: Prospective cohort study. SETTING: University of Chicago Medical Center general medicine wards. PARTICIPANTS: Community-dwelling inpatients aged 50 and older (N = 120) MEASUREMENTS: Physical activity and sleep were measured using wrist accelerometers. Information on Charlson Comorbidity Index and length of stay was collected from charts. Random-effects linear regression analysis was used to examine the association between in-hospital sleep and physical activity. RESULTS: From March 2010 to May 2013, 120 participants wore wrist actigraphy monitors for at least 2 nights and 1 intervening day. Median activity level over the waking period was 77 counts/min (interquartile range 51-121 counts/min), an activity level that approximately corresponds to sitting while watching television (65 counts/min). Mean sleep duration the night before the activity interval was 289 +/- 157 minutes, and mean sleep efficiency the night before the activity interval was 65.2 +/- 26.9%. Mean activity counts/min were lowest for the oldest participants (oldest quartile 62, 95% confidence interval (CI) = 50-75; youngest quartile 121, 95% CI = 98-145, trend test P < .001) and those with highest Charlson Comorbidity Index (highest tertile 71, 95% CI = 60-83; lowest tertile 125, 95% CI = 104-147, trend test P = .01). Controlling for severity of illness and demographic characteristics, activity declined by 3 counts/min (95% CI = 5.65 to -0.43, P = .02) for each additional hour of inpatient sleep. CONCLUSION: Older, sicker adults are less physically active during hospitalization. In contrast to studies in the community, inpatients who slept more were not more active. This may highlight that need for sleep is greater in the hospital than in the community. PMID- 26131984 TI - Seeing Is Believing. Sensing Real Progress in the Study of Human Airway Nerves. PMID- 26131978 TI - Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions. AB - BACKGROUND: The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. METHODS: A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010-2015). The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. FINDINGS: Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum gamma-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine. PMID- 26131985 TI - Television Advertising of Medicines. Unexpected Consequences? PMID- 26131983 TI - Emodin Inhibits Homocysteine-Induced C-Reactive Protein Generation in Vascular Smooth Muscle Cells by Regulating PPARgamma Expression and ROS-ERK1/2/p38 Signal Pathway. AB - Atherosclerosis is an inflammatory disease. As an inflammatory molecule, C reactive protein (CRP) plays a direct role in atherogenesis. It is known that the elevated plasma homocysteine (Hcy) level is an independent risk factor for atherosclerosis. We previously reported that Hcy produces a pro-inflammatory effect by inducing CRP expression in vascular smooth muscle cells (VSMCs). In the present study, we observed effect of emodin on Hcy-induced CRP expression in rat VSMCs and molecular mechanisms. The in vitro results showed that pretreatment of VSMCs with emodin inhibited Hcy-induced mRNA and protein expression of CRP in a concentration-dependent manner. The in vivo experiments displayed that emodin not only inhibited CRP expression in the vessel walls in mRNA and protein levels, but also reduced the circulating CRP level in hyperhomocysteinemic rats. Further study revealed that emodin diminished Hcy-stimulated generation of reactive oxygen species (ROS), attenuated Hcy-activated phosphorylation of ERK1/2 and p38, and upregulated Hcy-inhibited expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in VSMCs. These demonstrate that emodin is able to inhibit Hcy-induced CRP generation in VSMCs, which is related to interfering with ROS-ERK1/2/p38 signal pathway and upregulating PPARgamma expression. The present study provides new evidence for the anti-inflammatory and anti-atherosclerotic effects of emodin. PMID- 26131986 TI - Stress, ADCYAP1R1, and Childhood Asthma. No Sigh of Relief. PMID- 26131987 TI - Ventilator-associated Pneumonia Prevention. Is It Worth It? PMID- 26131988 TI - The Lungs and the Heart. PMID- 26131989 TI - Tailoring Therapy for Obesity Hypoventilation Syndrome. PMID- 26131990 TI - Inhaled Antibiotics for Refractory Nontuberculous Mycobacteria and Non-Cystic Fibrosis Bronchiectasis and the Significance of Mycobacterium abscessus subsp. abscessus Isolation during M. avium Complex Lung Disease Therapy. PMID- 26131991 TI - Reversed Halo Sign. A Case of Cryptogenic Organizing Pneumonia with Spontaneous Resolution. PMID- 26131992 TI - Aortic Expansion Assessed by Imaging Follow-up after Acute Aortic Syndrome: Effect of Sleep Apnea. PMID- 26131993 TI - Relationship between Change in Lung Density and Long-Term Progression of Lung Function. PMID- 26131994 TI - Reply: The Role of Immunohistochemistry in Diagnosis of Pulmonary Tumor Thrombotic Microangiopathy. PMID- 26131995 TI - The Role of Immunohistochemistry in Diagnosis of Pulmonary Tumor Thrombotic Microangiopathy. PMID- 26131997 TI - How Do the New Definitions for Multidrug-Resistant Tuberculosis Treatment Outcomes Really Perform? PMID- 26131996 TI - Reply: How Do the New Definitions for Multidrug-Resistant Tuberculosis Treatment Outcomes Really Perform? PMID- 26131998 TI - Contained Rupture of a Tuberculous Mycotic Aortic Aneurysm Detected by Bedside Ultrasound. PMID- 26131999 TI - Solidification of a Charged Colloidal Dispersion Investigated Using Microfluidic Pervaporation. AB - We investigate the dynamics of solidification of a charged colloidal dispersion using an original microfluidic technique referred to as micropervaporation. This technique exploits pervaporation within a microfluidic channel to extract the solvent of a dilute colloidal dispersion. Pervaporation concentrates the colloids in a controlled way up to the tip of the channel until a wet solid made of closely packed colloids grows and invades the microfluidic channel. For the charged dispersion under study, we however evidence a liquid to solid transition (LST) preceding the formation of the solid, owing to the presence of long-range electrostatic interactions. This LST is associated with the nucleation and growth of domains confined in the channel. These domains are then compacted anisotropically up to forming a wet solid of closely packed colloids. This solid then invades the whole channel as in directional drying with a growth rate which depends on the microfluidic geometry. In the final steps of the solidification, we observed the occurrence of cracks and shear bands, the delamination of the wet solid from the channel walls, and its invasion by a receding air front. Interestingly, this air front follows specific patterns within the solid which reveal different microscopic colloidal organizations. PMID- 26132000 TI - Using the PhenX Toolkit to Add Standard Measures to a Study. AB - The PhenX (consensus measures for Phenotypes and eXposures) Toolkit (https://www.phenxtoolkit.org/) offers high-quality, well-established measures of phenotypes and exposures for use by the scientific community. The goal is to promote the use of standard measures, enhance data interoperability, and help investigators identify opportunities for collaborative and translational research. The Toolkit contains 395 measures drawn from 22 research domains (fields of research), along with additional collections of measures for Substance Abuse and Addiction (SAA) research, Mental Health Research (MHR), and Tobacco Regulatory Research (TRR). Additional measures for TRR that are expected to be released in 2015 include Obesity, Eating Disorders, and Sickle Cell Disease. Measures are selected by working groups of domain experts using a consensus process that includes input from the scientific community. The Toolkit provides a description of each PhenX measure, the rationale for including it in the Toolkit, protocol(s) for collecting the measure, and supporting documentation. Users can browse measures in the Toolkit or can search the Toolkit using the Smart Query Tool or a full text search. PhenX Toolkit users select measures of interest to add to their Toolkit. Registered Toolkit users can save their Toolkit and return to it later to revise or complete. They then have options to download a customized Data Collection Worksheet that specifies the data to be collected, and a Data Dictionary that describes each variable included in the Data Collection Worksheet. The Toolkit also has a Register Your Study feature that facilitates cross-study collaboration by allowing users to find other investigators using the same PhenX measures. PMID- 26132001 TI - Glycosylation Analysis for Congenital Disorders of Glycosylation. AB - Congenital disorders of glycosylation (CDG) are a group of diseases with highly variable phenotypes and inconsistent clinical features. Since the first description of a CDG in 1980, approximately 100 disorders have been identified. Most of these are defects in protein glycosylation, although an increasing number are defects of glycolipid or proteoglycan biosynthesis. A group of biochemical markers has been used to characterize protein glycosylation abnormalities in CDG. This unit describes three protocols that can be used to measure plasma or serum carbohydrate deficient transferrin (CDT) profile, N-glycan profile, and O-glycan profile by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) or liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS). The quantification of particular biomarkers, such as T antigens or sialylated T antigens, could also be achieved by liquid chromatography-tandem mass spectrometry (LC-MS/MS). These techniques can be used to identify a majority of patients with defects in protein glycosylation, although different techniques, such as flow cytometry with immunostaining, are necessary to detect defects in glycolipid or proteoglycan biosynthesis which is not included in this unit. PMID- 26132002 TI - Determination of Activity of the Enzymes Hypoxanthine Phosphoribosyl Transferase (HPRT) and Adenine Phosphoribosyl Transferase (APRT) in Blood Spots on Filter Paper. AB - Hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency is the cause of Lesch-Nyhan disease. Adenine phosphoribosyl-transferase (APRT) deficiency causes renal calculi. The activity of each enzyme is readily determined on spots of whole blood on filter paper. This unit describes a method for detecting deficiencies of HPRT and APRT. PMID- 26132004 TI - Finding Pathogenic Nucleic Acid Sequences in Next Generation Sequencing Data. AB - Viruses and bacteria are established as one of the main causes of human diseases from hepatitis to cancer. Recently, the presence of such pathogens has been extensively studied using human whole genome and transcriptome sequencing data. However, detecting and studying pathogens via next generation sequencing data is a challenging task in terms of time and computational resources. In this protocol we give instructions for a simple and quick method to find pathogenic DNA or RNA and detect possible integration of the pathogen genome into the host genome. PMID- 26132005 TI - Differential success in sampling of Atlantic Forest amphibians among different periods of the day. AB - In general, anurans tend to be nocturnal, though diurnal activity is characteristic of some groups. Studies show that frog activity may be inferred based on the number of individuals collected at different periods of the day, during large-scale field surveys. We investigated the best period of the day to conduct amphibian sampling in nine Atlantic Rainforest areas in southeastern Brazil, based on intensive field surveys. At each locality we employed similar sampling effort during diurnal, crepuscular and nocturnal searches (totaling 704.5 sampling hours). We pooled data from all localities for each period and estimated the proportion of frogs of each species active at each period based on the total number of individuals and on the number of species found during all surveys for that period. We recorded a total of 817 individual frogs from 69 species. Species richness was highest at night (median = 12 species), intermediate at dusk (median = 8), and lowest during the day (median = 4). The percentage of the total number of individual frogs found (pooled species) was highest during the night (ca. 53%) and lowest during the day (ca. 14%). Analyzing each species separately, the number of individuals recorded was consistently higher at dusk and night for most species. Our study evidences a trend for nocturnal activity for most Atlantic Rainforest frogs, with few species having primarily diurnal habits. Those results may favor future studies and conservation efforts for amphibian species. PMID- 26132006 TI - Adequacy assessment of mathematical models in the dynamics of litter decomposition in a tropical forest Mosaic Atlantic, in southeastern Brazil. AB - The study of litter decomposition and nutrient cycling is essential to know native forests structure and functioning. Mathematical models can help to understand the local and temporal litter fall variations and their environmental variables relationships. The objective of this study was test the adequacy of mathematical models for leaf litter decomposition in the Atlantic Forest in southeastern Brazil. We study four native forest sites in Parque Estadual do Rio Doce, a Biosphere Reserve of the Atlantic, which were installed 200 bags of litter decomposing with 20 * 20 cm nylon screen of 2 mm, with 10 grams of litter. Monthly from 09/2007 to 04/2009, 10 litterbags were removed for determination of the mass loss. We compared 3 nonlinear models: 1 - Olson Exponential Model (1963), which considers the constant K, 2 - Model proposed by Fountain and Schowalter (2004), 3 - Model proposed by Coelho and Borges (2005), which considers the variable K through QMR, SQR, SQTC, DMA and Test F. The Fountain and Schowalter (2004) model was inappropriate for this study by overestimating decomposition rate. The decay curve analysis showed that the model with the variable K was more appropriate, although the values of QMR and DMA revealed no significant difference (p > 0.05) between the models. The analysis showed a better adjustment of DMA using K variable, reinforced by the values of the adjustment coefficient (R2). However, convergence problems were observed in this model for estimate study areas outliers, which did not occur with K constant model. This problem can be related to the non-linear fit of mass/time values to K variable generated. The model with K constant shown to be adequate to describe curve decomposition for separately areas and best adjustability without convergence problems. The results demonstrated the adequacy of Olson model to estimate tropical forest litter decomposition. Although use of reduced number of parameters equaling the steps of the decomposition process, no difficulties of convergence were observed in Olson model. So, this model can be used to describe decomposition curves in different types of environments, estimating K appropriately. PMID- 26132007 TI - Sensitivity of salad greens (Lactuca sativa L. and Eruca sativa Mill.) exposed to crude extracts of toxic and non-toxic cyanobacteria. AB - We evaluated the effect of crude extracts of the microcystin-producing (MC+) cyanobacteria Microcystis aeruginosa on seed germination and initial development of lettuce and arugula, at concentrations between 0.5 MUg.L(-1) and 100 MUg.L(-1) of MC-LR equivalent, and compared it to crude extracts of the same species without the toxin (MC-). Crude extracts of the cyanobacteria with MC (+) and without MC (-) caused different effects on seed germination and initial development of the salad green seedlings, lettuce being more sensitive to both extracts when compared to arugula. Crude extracts of M. aeruginosa (MC+) caused more evident effects on seed germination and initial development of both species of salad greens than MC-. Concentrations of 75 MUg.L(-1) and 100 MUg.L(-1) of MC LR equivalent induced a greater occurrence of abnormal seedlings in lettuce, due to necrosis of the radicle and shortening of this organ in normal seedlings, as well as the reduction in total chlorophyll content and increase in the activity of the antioxidant enzyme peroxidase (POD). The MC- extract caused no harmful effects to seed germination and initial development of seedlings of arugula. However, in lettuce, it caused elevation of POD enzyme activity, decrease in seed germination at concentrations of 75 MUg.L(-1) (MC-75) and 100 MUg.L(-1) (MC-100), and shortening of the radicle length, suggesting that other compounds present in the cyanobacteria extracts contributed to this result. Crude extracts of M. aeruginosa (MC-) may contain other compounds, besides the cyanotoxins, capable of causing inhibitory or stimulatory effects on seed germination and initial development of salad green seedlings. Arugula was more sensitive to the crude extracts of M. aeruginosa (MC+) and (MC-) and to other possible compounds produced by the cyanobacteria. PMID- 26132003 TI - Porphyria Diagnostics-Part 1: A Brief Overview of the Porphyrias. AB - Porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized by excessive accumulation and excretion of porphyrins and their precursors. Precisely which of these chemicals builds up depends on the type of porphyria. Porphyria is not a single disease but a group of nine disorders: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), delta-aminolevulinic acid dehydratase deficiency porphyria (ADP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and X-linked protoporphyria (XLP). Each porphyria results from overproduction of heme precursors secondary to partial deficiency or, in XLP, increased activity of one of the enzymes of heme biosynthesis. Taken together, all forms of porphyria afflict fewer than 200,000 people in the United States. Based on European studies, the most common porphyria, PCT, has a prevalence of 1 in 10,000, the most common acute porphyria, AlP, has a prevalence of ~1 in 20,000, and the most common erythropoietic porphyria, EPP, is estimated at 1 in 50,000 to 75,000. CEP is extremely rare, with prevalence estimates of 1 in 1,000,000 or less. Only six cases of ADP are documented. The current porphyria literature is very exhaustive and a brief overview of porphyria diseases is essential in order for the reader to better appreciate the relevance of this area of research prior to undertaking biochemical diagnostics procedures. This unit summarizes the current knowledge on the classification, clinical features, etiology, pathogenesis, and genetics of porphyria diseases. PMID- 26132008 TI - Oocyte quality of tambaqui (Colossoma macropomum) during the reproductive season. AB - The study aimed to analyze the Colossoma macropomum reproductive behavior and quality of the female gametes throughout the reproductive season. The experiment was carried out in Pimenta Bueno - Rondonia State (Northern Brazil) during the reproductive season (2010-2011) using 36 females. Each sampling was performed on a 15 +/- 5 days interval. Female gametes were collected by stripping and the following analyses were performed: weight of oocytes released (g); productivity index, fertilization and hatching rate. During the sampling period was verified effect (p < 0.05) of collecting time into the season for oocytes weight, productivity index and fertilization rate. Although the period 3 (December) did not differ significantly from other periods, it showed better parameters for the quality of C. macropomum oocytes. PMID- 26132009 TI - First report of the black gemfish Nesiarchus nasutus (Perciformes: Gempylidae) in Argentinean waters. AB - The gempylid Nesiarchus nasutus is reported for the first time from Argentinean waters, the southernmost occurrence of the species in the Southwestern Atlantic. This suggests that the fluctuating environmental characteristics of the area would be proper for the presence of tropical and subtropical species. PMID- 26132010 TI - Diet of the lizard Liolaemus occipitalis in the coastal sand dunes of southern Brazil (Squamata-Liolaemidae). AB - Knowledge of a species' diet provides important information on adaptation and the relationship between the organism and its environment. The genus Liolaemus occurs in the southern region of South America and is an excellent model to investigate the adaptive processes of vertebrate ecology in ecosystems of this region of the world. Liolaemus occipitalis is an endangered species that inhabits the coastal sand dunes of southern Brazil. This species is the most abundant vertebrate in this environment, and it presents unique adaptation characteristics to the restinga environment. The present study analyzed this lizard's diet to verify similarities or differences between this species and other species of the same genus. Specimens were collected monthly from January 1996 to December 1997. The number of items, frequency of occurrence and volume of each prey taxon were determined. Arthropods were identified to the order level, and plant material was identified as flower, fruit, seed and leaves. Variations in the diet of males and females, adults and juveniles and seasons were also analyzed. The data indicate that Liolaemus occipitalis is a generalist, "sit-and-wait" or ambush predator as well as omnivorous, feeding on both arthropods and plant material. Significant ontogenetic differences were verified. Juveniles are more carnivorous, and the intake of plant material increases with size and age. Seasonal differences in diet composition were also observed. In the spring, arthropod and plant materials were more diversified and, therefore, consumed more often. PMID- 26132011 TI - Frugivory and potential of birds as dispersers of Siparuna guianensis. AB - Siparuna guianensis is a neotropical tree species, found both on edge and interior of forest fragments, mainly on understory and regeneration areas. The fruit are zoochorous with a sweet aril. This work aims to determine the bird species that eat the fruits of S. guianensis in a semi deciduous forest fragment in Brazilian Cerrado and measure which species have the highest potential as seed dispersers. Seven individuals of S. guianensis were sampled, totaling 69 hours. A hundred and fifty four visits were registered by seven species of birds. Antilophia galeata had the biggest potential as seed dispersal agent. Antilophia galeata, Lanio penicillatus and Dacnis cayana can be important seed dispersers, since they have a high consumption and visitation rate. The consumption of S. guianensis by species of different feeding guilds can be an important strategy for dispersal of plant species in regeneration habitats, raising the chances of an effective dispersal. PMID- 26132012 TI - Population biology of the commercially exploited shrimp Artemesia longinaris (Decapoda: Penaeidae) in an upwelling region in the Western Atlantic: comparisons at different latitudes. AB - This study characterized the population biology of the dendrobranchiate penaeid shrimp Artemesia longinaris Spence Bate, 1888, focusing on population structure, sexual maturity, reproductive period and recruitment, and comparing reproductive parameters of a different populations along western South Atlantic. Samples were collected monthly from March, 2008 to February, 2010 in Macae, northern coast of Rio de Janeiro State, Brazil, a region influenced by the Cabo Frio upwelling. There was a significantly higher percentage of females and with larger sizes than males. Both carapace length and sexual maturity in Macae were similar to the dimensions found in populations in the South of the continent (Argentina). Reproductive females were present in all months, with main peaks during winter and summer. Recruitment was also continuous, with peaks, usually one to two months after the appearance of reproductive females, after the reduction of the bottom temperature values of water. These data suggest that November to January would be the appropriate months for legal off-season, due to the higher intensity of spawning females and juveniles during this period. The results of this study contribute to the understanding of the biology of A. longinaris, and could also be a reference to monitor this important fishery resource and consequent legal off-season. Furthermore, this population located at the northern limit of the species distribution is a source of highly relevant comparison for population studies in other areas. PMID- 26132013 TI - Modeling pollution potential input from the drainage basin into Barra Bonita reservoir, Sao Paulo - Brazil. AB - In this study multi-criteria modeling tools are applied to map the spatial distribution of drainage basin potential to pollute Barra Bonita Reservoir, Sao Paulo State, Brasil. Barra Bonita Reservoir Basin had undergone intense land use/land cover changes in the last decades, including the fast conversion from pasture into sugarcane. In this respect, this study answers to the lack of information about the variables (criteria) which affect the pollution potential of the drainage basin by building a Geographic Information System which provides their spatial distribution at sub-basin level. The GIS was fed by several data (geomorphology, pedology, geology, drainage network and rainfall) provided by public agencies. Landsat satellite images provided land use/land cover map for 2002. Ratings and weights of each criterion defined by specialists supported the modeling process. The results showed a wide variability in the pollution potential of different sub-basins according to the application of different criterion. If only land use is analyzed, for instance, less than 50% of the basin is classified as highly threatening to water quality and include sub basins located near the reservoir, indicating the importance of protection areas at the margins. Despite the subjectivity involved in the weighing processes, the multi criteria analysis model allowed the simulation of scenarios which support rational land use polices at sub-basin level regarding the protection of water resources. PMID- 26132014 TI - Gonad development and reproduction of the ballyhoo half beak, Hemiramphus brasiliensis from the coastal waters of Rio Grande do Norte, Brazil. AB - The gonad development and reproductive aspects of Hemiramphus brasiliensis from the coastal waters of Rio Grande do Norte, Brazil were verified. This paper presents data on the length-weight relationship, sex ratio, length at first sexual maturity, gonad development, reproductive period and fecundity of H. brasiliensis. Females of this species predominated in the sampled population and were larger in size than the males. The length at the first sexual maturation of males was 20.8 cm and that of females was 21.5 cm. The macroscopic characteristics of the gonads indicated four maturation stages. Histological studies of gonads of H. brasiliensis showed six phases of oocyte development and four phases of spermatocyte development. The batch fecundity of this species is 1153 (+/- 258.22) oocytes for 50 g body weight of female. The microscopic characteristics of gonad development indicate that H. brasiliensis is a multiple spawner, with active reproductive period during the months of January to June and October. The reproductive period of this species is independent of the rainy period of the region. PMID- 26132015 TI - Diffusive emission of methane and carbon dioxide from two hydropower reservoirs in Brazil. AB - The role of greenhouse gas emissions from freshwater reservoirs and their contribution to increase greenhouse gas concentrations in the atmosphere is currently under discussion in many parts of the world. We studied CO2 and CH4 diffusive fluxes from two large neotropical hydropower reservoirs with different climate conditions. We used floating closed-chambers to estimate diffusive fluxes of these gaseous species. Sampling campaigns showed that the reservoirs studied were sources of greenhouse gases to the atmosphere. In the Serra da Mesa Reservoir, the CH4 emissions ranged from 0.530 to 396.96 mg.m(-2).d(-1) and CO2 emissions ranged from -1,738.33 to 11,166.61 mg.m(-2).d(-1) and in Tres Marias Reservoir the CH4 fluxes ranged 0.720 to 2,578.03 mg.m(-2).d(-1) and CO2 emission ranged from -3,037.80 to 11,516.64 to mg.m(-2).d(-1). There were no statistically significant differences of CH4 fluxes between the reservoirs, but CO2 fluxes from the two reservoirs studied were significantly different. The CO2 emissions measured over the periods studied in Serra da Mesa showed some seasonality with distinctions between the wet and dry transition season. In Tres Marias Reservoir the CO2 fluxes showed no seasonal variability. In both reservoirs, CH4 emissions showed a tendency to increase during the study periods but this was not statistically significant. These results contributed to increase knowledge about the magnitude of CO2 and CH4 emission in hydroelectric reservoirs, however due to natural variability of the data future sampling campaigns will be needed to better elucidate the seasonal influences on the fluxes of greenhouse gases. PMID- 26132016 TI - Functional leaf traits of understory species: strategies to different disturbance severities. AB - The specific leaf area (SLA) has been related to environmental disturbances, showing a positive correlation between the disturbances intensities and SLA in a plant community. These studies, however, assessed the responses of plant community as a whole, neglecting species attributes, such as the position in the vertical stratum of forests. Considering the importance of SLA to understand forest ecological processes, this study aimed to determine the influence of the disturbance regime on the SLA of understory species, considering that, unlike for communities as a whole, an increase in the disturbance intensity implies a decrease in SLA of understory species. This study was conducted in nine understories of seasonal forests in Brazil. The most abundant species were selected and their SLA were evaluated. The variability of SLA among populations in different forests was analyzed by Student's t-tests. The SLA of the understories (SLAU) was also compared by an adaptation of the Community-weighted mean index. The comparison of species SLA showed significant differences among the populations of understories under different disturbance regime, showing a decrease in SLA with an increase in the disturbance intensity. Similar results were found for the SLA of understories communities (SLAU), corroborating our hypothesis. The correlation between a reduction in species SLA and in SLA of understory with an increase in disturbance intensity, contradicted the trend observed in the literature for the community as a whole. This study highlights the importance of the evaluation of SLA in understories, as an indicator of the successional stage of communities. PMID- 26132017 TI - Edge effect on post-dispersal artificial seed predation in the southeastern Amazonia, Brazil. AB - This paper evaluates the post-dispersal artificial seed predation rates in two areas of the southeastern Amazon forest-savanna boundary, central Brazil. We conducted the survey in a disturbance regime controlled research site to verify if exists an edge effect in these rates and if the disturbance (in this case annual fire and no fire) affects seed predation. We placed 800 peanuts seeds in each area at regular distance intervals from the fragment's edge. Data were analyzed by a likelihood ratio model selection in generalized linear models (GLM). The complete model (with effects from edge distance and site and its interaction) was significative (F3=4.43; p=0.005). Seeds had a larger predation rates in fragment's interior in both areas, but in the controlled area (no disturbance) this effect was less linear. This suggests an edge effect for post dispersal seed predation, and that disturbances might alter these effects. Even if we exclude the site effect (grouping both areas together) there is still a strong edge effect on seed predation rates (F3=32.679; p>0.001). We did not verify predator's species in this study; however, the presence of several species of ants was extremely common in the seeds. The detection of an edge effect in only a short survey time suggests that there is heterogeneity in predation rates and that this variation might affect plant recruitment in fragmented areas of the Amazon forest. Henceforth, this seed predation should be taken in consideration in reforestation projects, where the main source of plants species is from seed distribution. PMID- 26132018 TI - Diel vertical migration and spatial overlap between fish larvae and zooplankton in two tropical lakes, Brazil. AB - The effect of fish larvae on the diel vertical migration of the zooplankton community was investigated in two tropical lakes, Finado Raimundo and Pintado lakes, Mato Grosso do Sul State, Brazil. Nocturnal and diurnal samplings were conducted in the limnetic region of each lake for 10 consecutive months from April 2008 to January 2009. The zooplankton community presented a wide range of responses to the predation pressure exerted by fish larvae in both environments, while fish larvae showed a typical pattern of normal diel vertical migration. Our results also demonstrated that the diel vertical migration is an important behaviour to avoid predation, since it reduces the spatial overlap between prey and potential predator, thus supporting the hypothesis that vertical migration is a defence mechanism against predation. PMID- 26132019 TI - Acetylcholine produces contraction mediated by cyclooxigenase pathway in arterial vessels in the marine fish (Isacia conceptionis). AB - Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (G. laevifrons). Our objective was to characterize the cholinergic pathway in several artery vessels of the I. conceptionis. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using doses response curves (DRC) for Ach (10(-13) to 10(-3) M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high sensitivity only in efferente branchial artery and low sensibility in all vessels. Furthermore, these contractions were blocked in the presence of atropine and indomethacin in all vessels. Our results corroborate previous results observed in intertidal species that contraction induced by acetylcholine is mediated by receptors that activate a cyclooxygenase contraction pathway. PMID- 26132020 TI - Origin of the subepidermal tissue in Piper L. leaves. AB - Studies on the anatomy of Piper leaves demonstrate the presence of a subepidermal tissue distinct from the adjacent epidermis, which cells show thin walls and hyaline contents. Some authors consider such cells a hypodermal tissue, while others refer to them as components of a multiple epidermis. In this study, the nature of this subepidermal tissue was investigated through the analysis of leaf ontogeny in three Piper species. The analysis showed that the referred tissue originates from the ground meristem and, thus, should be considered a hypodermis. The studied species suggests that the role of the hypodermis would be to protect the photosynthetic apparatus from excess light, regulating the intensity of light reaching the chlorophyll parenchyma. PMID- 26132021 TI - Effect of salinity on the metabolism and osmoregulation of selected ontogenetic stages of an Amazon population of Macrobrachium amazonicum shrimp (Decapoda, Palaemonidae). AB - Probably as a function of their wide geographical distribution, the different population of Macrobrachium amazonicum shrimp may present distinct physiological, biochemical, reproductive, behavioral, and ecological patterns. These differences are so accentuated that the existence of allopatric speciation has been suggested, although initial studies indicate that the genetic variability of populations happen at an intraspecific level. Among the biological responses described for M. amazonicum populations, those regarding osmoregulation and metabolism play a key role for being related to the occupation of diverse habitats. To this effect, we investigated osmoregulation through the role of free amino acids in cell volume control and metabolism, through oxygen consumption in larvae (zoeae I, II, V and IX) and/or post-larvae of a M. amazonicum population from Amazon, kept in aquaculture fish hatcheries in the state of Sao Paulo. The results add information regarding the existence of distinct physiological responses among M. amazonicum populations and suggest that possible adjustments to metabolism and to the use of free amino acids as osmolytes of the regulation of the larvae and post-larvae cell volume depend on the appearance of structures responsible for hemolymph osmoregulation like, for example, the gills. In this respect, we verified that zoeae I do not alter their metabolism due to the exposition to fresh or brackish water, but they reduce intracellular concentration of free amino acids when exposed to fresh water, what may suggest the inexistence or inefficient performance of the structures responsible for volume regulation and hemolymph composition. On the other hand, in zoeae II and V exposed to fresh and brackish water, metabolism alterations were not followed by changes in free amino acids concentration. Thus it is possible, as the structures responsible for osmoregulation and ionic regulation become functional, that the role of free amino acids gets diminished and oxygen consumption elevated, probably due to greater energy expenditure with the active transportation of salts through epithelial membranes. Osmotic challenges also seem to alter throughout development, given that in zoeae II oxygen consumption is elevated on brackish water of 18, but in zoeae V it happens in fresh water. After M. amazonicum metamorphosis, free amino acids begin to play an important role as intracellular osmolytes, because we verified an increase of up to 40% in post larvae exposed to brackish water of 18. The main free amino acids involved in cell volume regulation of ontogenetic stages evaluated were the non essential ones: glutamic acid, glycine, alanine, arginine, and proline. Interestingly, larvae from estuarine population studied here survived until the zoeae V stage in fresh water, but in some populations far from the sea, zoeae die right after eclosion in fresh water or they do not reach zoeae III stage. In addition, given that in favorable conditions caridean shrimp larvae shorten their development, we may infer that the cultivation environment, in which larvae developed in the present work, was appropriate, because almost all zoeae VIII kept on brackish water underwent metamorphosis directly to post-larvae and did not go through zoeae IX stage. PMID- 26132022 TI - Differences in ichthyofauna feeding habits among lateral lagoons and the river channel in a large reservoir. AB - In this study, we investigated differences in feeding habits of small-sized ichthyofauna among lateral lagoons and the river channel in a large reservoir. The study was performed in four lagoons and in one sampling site of the main channel in Rosana Reservoir, Paranapanema River, Brazil. The samples were taken in September and November of 2004 and in January, March, May, and August of 2005. Fish were sampled with a 7.5 m2 hand net. Five manual throws were made toward aquatic macrophytes stands. The sampling design favored the collection of small sized fish fauna (juveniles/small-sized species). The stomach contents of 42 species were analyzed. A total of 183 different items were consumed by fish. These items were grouped in 11 food categories, which were used to classify fish into seven trophic guilds. Aquatic insects were consumed by 32 species and were the predominant feeding item. In the river, the most consumed items were aquatic insects, cladocerans, and phytoplankton, whereas in the lagoons aquatic insects, copepods, and cladocerans were the main items. By comparing each trophic guild, the number of insectivores, algivores, and zooplanktivores species was higher in the lagoons than in the river, and the opposite was found only for omnivore fish. Low niche width in all sites indicates high trophic specialization and low niche overlap between pairs of species. Fish assemblage in the lateral lagoons presents feeding habits distinct from those of the river species, indicating that the coexistence and high abundance of small-sized fish in the sampling sites are explained by their high feeding adaptability, which includes a tendency toward dietary specialization, low feeding overlap, and resource partitioning, along with different temporal resource uses. PMID- 26132023 TI - Molecular identification of Trichogramma species from regions in Brazil using the sequencing of the ITS2 region of ribosomal DNA. AB - The objective of this work was the identification and differentiation of Trichogramma exiguum Pinto and Platner species, T. pretiosum Riley, and T. galloi Zucchi using sequences of the ITS2 region of ribosomal DNA. After extracting DNA from the studied species, a PCR reaction was performed, where the amplified samples were subjected to sequencing. The sequences obtained were submitted to a similarity search in GenBank (NCBI - National Center for Biotechnology Information) using the BLAST program, aiming to determine the similarity of these sequences with the species already deposited in the referenced database, and then multiple sequences were aligned using version 2.0 of the ClustalX program. According to the results of the multiple alignments of all sequences obtained, it was possible to observe the differences between the T. pretiosum, T. galloi and T. exiguum species. It was concluded that using the sequences of the ITS2 region of the ribosomal DNA was efficient in the differentiation of the studied Trichogramma species, which suggests a strong inter-specific variation among species. PMID- 26132024 TI - Influence of agricultural environment on the plant mite community in forest fragments. AB - The mite community has been surveyed in Seasonal Semideciduous Forest with three types of surrounding agricultural environments to test the hypothesis that abundance and richness of mites in forest fragments are influenced by the type of agricultural environment. The survey has been carried out in six fragments, divided into sets of two fragments, each one neighboring one sort of agricultural environment: sugarcane crop (FS), orange crop (FO) and pasture (FP). In each fragment, ten individuals of Actinostemon communis (Euphorbiaceae) were selected, five at the edge and five within each fragment. Iphiseiodes zuluagai, often registered in orange crops, was more abundant in the fragments neighboring such crop, as well as some species of Tarsonemidae. In this study, the Phytoseiidae were more abundant in the fragments neighboring pasture, while sugarcane crops probably favored occurrence of phytophagous mites in the neighboring fragments. Tetranychidae were less abundant in FO, which can be explained by periodical use of pesticides in the orange crops. Forest fragments are important for colonies of predators in the neighboring crops, mainly for annual crops such as sugarcane, where the close perennial environment is very important for colonization of the crop. Maintenance of those areas, besides favoring preservation of wild species of mite, is very important to increase diversity of the neighboring agricultural ecosystems. PMID- 26132025 TI - Experimental manipulation of leaf litter colonization by aquatic invertebrates in a third order tropical stream. AB - Through a manipulative experiment, the colonization of leaf litter by invertebrates was investigated in two sections of a tropical stream (spatial scale) that differed in function of the canopy cover, one with the presence (closed area) and another without riparian vegetation (open area), during one month of the dry and one of the wet season (temporal scale). The work aimed to verify differences related to four variables: season, canopy cover, leaf type and leaf condition. Litter bags containing arboreal and herbaceous leaves (leaf type variable), non-conditioned and preconditioned (leaf condition variable) were placed at the bottom of the stream in each area (canopy cover variable) and season (dry and wet), and removed after 13-day colonization. The analysis of the remaining litter dry mass per leaf bag emphasizes differences related mainly to seasonality, canopy cover and leaf type, although leaf condition was also important when combined with those three factors. Comparing the abundance of invertebrates per treatment, there was a tendency of high predominance of Chironomidae during the dry season and greater taxa diversity and evenness during the wet season, when the water flow increase could alter the availability of microhabitats for local fauna. Even though canopy cover alone was not a significant source of variation in the abundance of invertebrates, the results showed a tendency of a combined effect of canopy cover with seasonality and leaf condition. PMID- 26132026 TI - Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice. AB - AIMS: The present study verified the effect of propolis alone and its association with swimming in dyslipidemia, left ventricular hypertrophy and atherogenesis of hypercholesterolemic mice. METHODS AND RESULTS: The experiments were performed in LDLr-/- mice, fed with high fat diet for 75 days, and were divided into four experimental groups (n=10): HL, sedentary, subjected to aquatic stress (5 min per day, 5 times per week); NAT submitted to a swimming protocol (1 hour per day, 5 times per week) from the 16th day of the experiment; PRO, sedentary, submitted to aquatic stress and which received oral propolis extract (70 uL/animal/day) from the 16th day of the experiment; HL+NAT+PRO, submitted to swimming and which received propolis as described above. After 75 days, blood was collected for analysis of serum lipids. The ratio between the ventricular weight (mg) and the animal weight (g) was calculated. Histological sections of the heart and aorta were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process; stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations. The HL animals showed severe dyslipidemia, atherogenesis and left ventricular hypertrophy, associated with a decrease in serum HDLc levels and subsequent development of cardiovascular inflammatory process, characterized by increased expression of CD40L in the left ventricle and aorta. Swimming and propolis alone and?or associated prevented the LVH, atherogenesis and arterial and ventricular inflammation, decreasing the CD40L expression and increasing the HDLc plasmatic levels. CONCLUSION: Propolis alone or associated with a regular physical activity is beneficial in cardiovascular protection through anti-inflammatory action. PMID- 26132027 TI - Feeding habits of the congeneric species Stellifer rastrifer and Stellifer brasiliensis (Acanthopterygii: Sciaenidae) co-occurring in the coast of the state of Santa Catarina, Brazil. AB - The objective of the present study was to investigate the feeding habits allowing the occurrence of the congeneric species Stellifer rastrifer and Stellifer brasiensis, collected on a seasonal basis, in the operating area of the artisanal seabob-shrimp trawl fishery in Porto Belo, an important fishing area on the southern Brazilian coast. Fish were collected seasonally from November 2009 to August 2010, in isobaths of 10, 20 and 30 m. Of the 450 stomachs analyzed, 194 belonged to Stellifer rastrifer and 242 to Stellifer brasiliensis. From the totality of analyzed stomachs 33.49% were empty and 66.52% had some content. Crustacea were the predominant food category in the diet of S. rastrifer and S. brasiliensis, and the shrimp Acetes americanus was the most frequent crustacean in stomachs of both studied species. The overlapping in the diet of the species was high, however when analyzing the overlap in each season it was found that it occurred only during spring and winter. Although the most important items in the diet of these species are the same, the intake of each alternates in time, suggesting a difference in predation pressure, which leads to less direct competition in a given time. PMID- 26132028 TI - Alcanivorax dieselolei, an alkane-degrading bacterium associated with the mucus of the zoanthid Palythoa caribaeorum (Cnidaria, Anthozoa). AB - Analyses of 16S rDNA genes were used to identify the microbiota isolated from the mucus of the zoanthid Palythoa caribaeorum at Porto de Galinhas on the coast of Pernambuco State, Brazil. This study is important as the first report of this association, because of the potential biotechnological applications of the bacterium Alcanivorax dieselolei, and as evidence for the presence of a hydrocarbon degrading bacterium in a reef ecosystem such as Porto de Galinhas. PMID- 26132029 TI - Ontogenetic allometry in the foot size of Oligoryzomys flavescens (Waterhouse, 1837) (Rodentia, Sigmodontinae). AB - Ontogenetic allometry is the study of how the size or shape of certain structures changes over the course of an animal's development. In this study, using Huxley's formula of allometric growth (1932), we assessed the changes in the rate of growth of the feet size of the sigmodontine rodent Oligoryzomys flavescens during its ontogeny and compared differences between males and females. We find evidence of a change of polarity during the ontogenetic development of the species, with the presence of positive allometry during pregnancy and negative allometry in adulthood. Moreover, we note the presence of sexual dimorphism in the size of the feet, in which males of the species have a higher rate of growth than females. This growth pattern is positively related to escape from predators in childhood in both sexes and, in adulthood, provides a higher encounter rate of females by males, due to the larger displacement of the latter. We suggest that both the forces of natural selection and sexual selection have acted to shape the evolution of foot size in this species. PMID- 26132030 TI - Dexamethasone action on caudal fin regeneration of carp Cyprinus carpio (Linnaeus, 1758). AB - Studies have demonstrated that the prolonged use of corticoids can delay the healing process, affecting re-epithelialization, neovascularization and collagen synthesis. As the fins of teleost fish contain a large amount of collagen, the aim of the present study was to investigate the effect of dexamethasone (anti inflammatory and glucocorticoid steroid widely used in the treatment of rheumatic diseases) during the regeneration process in the caudal fin of specimens of carp (Cyprinus carpio). For such, two glass aquaria were used - one for a group of fish treated with dexamethasone (Henrifarma) in a 20 mg/L concentration and the other for the control group. The caudal fins were amputated transversally and fish remained in their respective aquaria until regeneration occurred. Samples of regenerating fins were collected on days 1, 2, 4, 6, 8 and 10 after amputation. The fins in the control group regenerated normally and grew within the expected in time course. The fins in the group treated with dexamethasone were significantly smaller in comparison to the control group at every evaluation time. Thus, it was possible to verify that, at this concentration of dexamethasone, the regeneration of the caudal fins was delayed, but not completely inhibited. The results show that the caudal fin is a good model for histological studies on regeneration and the action of drug toxicity, but it's also of great importance the interaction with further studies for a better knowledge and understanding of all the changes in all the phases. PMID- 26132031 TI - First records of Charadrius semipalmatus, Bonaparte 1825 (Charadriidae) and Gelochelidon nilotica Gmelin 1789 (Sternidae) in the State of Minas Gerais, Brazil. AB - Around forty bird species habitually reproduce in the Northern Hemisphere during summer, and migrate to the Southern Hemisphere during northern winter. These migrating birds fly together in large or small groups until they have reached the Caribbean, Central American, or Brazilian shores. Charadrius semipalmatus, Bonaparte 1825, is one of these migrating species that uses resting and feeding areas along eastern and western coasts of North and South America, with several records for the Brazilian coast, and very few for the inland country. On November 24, 2011, an individual of this species was observed on the banks of one of the lakes that compose a complex of about 40 temporary lakes within the Karst of Lagoa Santa Environmental Protection Area. On October 29 and 30, 2012 a single individual of Gelochelidon nilotica, Gmelin 1789, was also observed in Sumidouro State Park. We suggest that these specimens have used the Atlantic Ocean migration route, following the Sao Francisco River Basin, until the karst area. Although highly impacted, the temporary lakes within the Karst of Lagoa Santa still harbor a significant number of bird species, and serve as resting and feeding places for migratory or errant species that are still eliciting new records. PMID- 26132032 TI - Two new species of Dryinidae (Hymenoptera: Chrysidoidea) from areas of Atlantic Rainforest at Sao Paulo State, Brazil. AB - Two new species of Dryinidae are described and illustrated Dryinus auratus Martins, Lara, Perioto & Olmi sp. nov. and Gonatopus mariae Martins, Lara, Perioto & Olmi sp. nov., both from areas of Atlantic Rainforest at Sao Paulo State, Brazil. Keys to species are provided. PMID- 26132033 TI - Planktonic production and respiration in a subtropical lake dominated by Cyanobacteria. AB - Planktonic primary production and respiration rates were estimated in a subtropical coastal lake dominated by Cyanobacteria in order to investigate the temporal and vertical variation in this lake and to evaluate its relationships with limnological variables and phytoplankton. Light and dark bottles were incubated at four different depths in the central part of the lake and were performed bimonthly from June/2009 to December/2010. No significant difference was evident among depths in relation to phytoplankton, limnological variables and metabolic rates. However, the highest production rates were recorded at the surface, and decreased towards the bottom, coupled with phytoplanktonic photosynthetic capacity. Wind induced mixing in Peri Lake played an important role in nutrient and phytoplankton redistribution, characterizing this lake as polymictic. According to density and biovolume, the phytoplankton community was dominated by filamentous Cyanobacteria, especially Cylindrospermopsis raciborskii (Woloszynska) Seenayya and Subba-Raju. This study has shown that both water temperature and nutrient availability drive phytoplankton growth and consequently the temporal variation in metabolic rates, where respiration is higher than primary production. PMID- 26132034 TI - Antioxidant and genotoxic properties of Maytenus dasyclada: a comparative study in relation to Maytenus reference species. AB - In these work the in vitro antioxidant activity and the in vivo genotoxicity of M. dasyclada was compared to the reference species M. aquifolium and M. ilicifolia. M. dasyclada showed in vitro antioxidant activity comparable to M. aquifolium but lower than M. ilicifolia, being that a inverse Pearson correlation between DPPH IC50 values and total phenolic content was detected (-0.932). The carbonyl content of M. dasyclada and M. aquifolium extracts promoted a similar increase in protein oxidation in vivo, while M. ilicifolia no altered the carbonyl levels. The comet assay demonstrated that the three analyzed species promoted a low and similar level of genotoxicity; which is compatible with DNA damage induced by other medicinal plants and is partially recovered by a co treatment with vitamin C. The data showed M. dasyclada as antioxidant activity in vitro, and that its genotoxic and pro-oxidant effects in vivo are comparable to the Maytenus reference species. PMID- 26132035 TI - Lead tolerance and accumulation in initial sporophytes of Regnellidium diphyllum Lindm. (Marsileaceae). AB - Regnellidium diphyllum Lindm. is a heterosporous fern which grows in shallow waters and wetlands, and water pollution contributes to its vulnerability. Environmental lead contamination is mostly caused by industrial and agricultural residues as well as domestic sewage. Given its persistence in the environment, lead can cause important toxicity in living organisms. Megaspore germination and the initial growth of R. diphyllum sporophytes were assessed in Meyer's solution with lead nitrate (Pb(NO3)2) concentrations of 0 (control), 1, 5, 10 and 50 mg L( 1). The study was conducted in a growth chamber at 25 +/- 1 degrees C and a 12 hour photoperiod with a nominal irradiance of 100 MUmol m(-2) s(-1), for 28 days. Lead concentration in sporophytes was assessed using atomic absorption spectrometry. In the absence of lead, 74% of spores germinated, while significantly lower germination percentages were observed in Pb(NO3)2 concentrations of 1, 10 and 50 mg L(-1). The presence of lead did not significantly influence root growth. At 28 days, primary leaf development was significantly lower in Pb(NO3)2 concentrations of 5 mg L(-1) and higher in relation to the control. The length of secondary leaves did not significantly differ between sporophytes exposed to different concentrations of lead and those of the control at 28 days. Sporophytes exposed to 10 and 50 mg L(-1) Pb(NO3)2 accumulated 1129 mg kg(-1) and 5145 mg kg(-1) of Pb, respectively. The presence of high levels of lead in R. diphyllum sporophytes did not prevent initial development. Future studies should investigate the ability of the species to accumulate and tolerate high levels of lead in advanced stages of its development and in environmental conditions. PMID- 26132036 TI - Conservation status of an endangered annual fish Hypsolebias antenori (Rivulidae) from Northeastern Brazil. AB - This work presents information regarding the biology and state of conservation of an endangered annual fish Hypsolebias antenori. Fish were captured from small seasonal pools located in Northeastern Brazil. The total body length, body mass, sex ratio, first sexual maturity were investigated. The sampled population showed sexual dimorphism. There was a predominance of females (60%) over males (40%) with a sex ratio of 1: 1.4 and males were bigger and heavier than the females. Amplitude of total length of males ranged from 2.6 to 7.1cm (4.1 +/- 1.15) and that of females from 2.2 to 5.4 cm (3.6 +/- 0.9). Amplitude of body mass of males varied from 0.25 to 7 g (1.3 g +/- 1.4) and that of females from 0.12 to 2.1g (0.7 g +/- 0.5). The total weight-length equation of males was Wt = 0.0108Lt3.172 with r = 0.9826 and of females was Wt = 0.0122Lt3.0114 with r = 0.9608. Females attained first sexual maturity at 3.2 cm (+/- 0.25) total length and males at 3.3 cm (+/- 0.08) total length. All temporary pools surveyed in Northeastern Brazil were in a high degree of degradation, suffering due to anthropogenic action. Reduced rainfall resulting from global climate change prevents the filling up of these pools, thus preventing the completion of the reproductive cycle of annual fishes. One factor hindering development of conservation strategies is limited literature on biology and conservation status of annual fishes. There is a need for conservation measures to protect annual fish populations, especially creation of protected areas in the Brazilian semiarid region. PMID- 26132037 TI - Acute inflammation and hematological response in Nile tilapia fed supplemented diet with natural extracts of propolis and Aloe barbadensis. AB - This study evaluated the acute inflammatory response induced by carrageenin in the swim bladder of Nile tilapia supplemented with the mixture of natural extracts of propolis and Aloe barbadensis (1:1) at a concentration of 0.5%, 1% and 2% in diet during 15 days. Thirty-six fish were distributed into four treatments with three replicates: fish supplemented with 0.5% of admix of extracts of propolis and Aloe (1:1) injected with 500 ug carrageenin; fish supplemented with 1% of admix of extracts of propolis and Aloe (1:1) injected with 500 ug carrageenin; fish supplemented with 2% of admix of extracts of propolis and Aloe (1:1), injected with 500 ug carrageenin and unsupplemented fish injected with 500 ug carrageenin. Six hours after injection, samples of blood and exudate from the swim bladder of fish were collected. It was observed an increase in the leukocyte count in the swim bladder exudate of fish supplemented with extracts of propolis and Aloe injected with carrageenin. The most frequent cells were macrophages followed by granular leukocytes, thrombocytes and lymphocytes. Supplementation with propolis and Aloe to 0.5% caused a significant increase in the number of cells on the inflammatory focus mainly macrophages, cells responsible for the phagocytic activity in tissues, agent of innate fish immune response. PMID- 26132038 TI - First record of Sebekia oxycephala (Pentastomida: Sebekidae) infecting Helicops infrataeniatus (Reptilia: Colubridae), Sao Paulo State, Brazil. PMID- 26132039 TI - First report of citrus blackfly (Hemiptera: Aleyrodidae) in the state of Piaui, Brazil. PMID- 26132040 TI - Differential aerobic decomposition between a native and exotic macrophytes of tropical reservoirs. PMID- 26132041 TI - Heterologous induction of a predicted promoter sequence for paraquat-inducible genes of Chromobacterium violaceum in response to paraquat compound. PMID- 26132042 TI - First record of Tachinaephagus zealandicus Ashmead, 1904 (Hymenoptera: Encyrtidae) parasitizing the blowfly Sarconesia chlorogaster (Wiedemann, 1830) (Diptera: Calliphoridae) in Brazil. PMID- 26132044 TI - Erratum. PMID- 26132043 TI - A bloom of cyanobacteria (Cylindrospermopsis raciborskii) in UHE Carlos Botelho (Lobo/Broa) reservoir: a consequence of global change? PMID- 26132046 TI - Structure-Based Assignment of Ile, Leu, and Val Methyl Groups in the Active and Inactive Forms of the Mitogen-Activated Protein Kinase Extracellular Signal Regulated Kinase 2. AB - Resonance assignments are the first step in most NMR studies of protein structure, function, and dynamics. Standard protein assignment methods employ through-bond backbone experiments on uniformly (13)C/(15)N-labeled proteins. For larger proteins, this through-bond assignment procedure often breaks down due to rapid relaxation and spectral overlap. The challenges involved in studies of larger proteins led to efficient methods for (13)C labeling of side chain methyl groups, which have favorable relaxation properties and high signal-to-noise. These methyls are often still assigned by linking them to the previously assigned backbone, thus limiting the applications for larger proteins. Here, a structure based procedure is described for assignment of (13)C(1)H3-labeled methyls by comparing distance information obtained from three-dimensional methyl-methyl nuclear Overhauser effect (NOE) spectroscopy with the X-ray structure. The Ile, Leu, or Val (ILV) methyl type is determined by through-bond experiments, and the methyl-methyl NOE data are analyzed in combination with the known structure. A hierarchical approach was employed that maps the largest observed "NOE-methyl cluster" onto the structure. The combination of identification of ILV methyl type with mapping of the NOE-methyl clusters greatly simplifies the assignment process. This method was applied to the inactive and active forms of the 42-kDa ILV (13)C(1)H3-methyl labeled extracellular signal-regulated kinase 2 (ERK2), leading to assignment of 60% of the methyls, including 90% of Ile residues. A series of ILV to Ala mutants were analyzed, which helped confirm the assignments. These assignments were used to probe the local and long-range effects of ligand binding to inactive and active ERK2. PMID- 26132048 TI - The Effects of Music Intervention on Background Pain and Anxiety in Burn Patients: Randomized Controlled Clinical Trial. AB - This study aimed to investigate the effect of music on the background pain, anxiety, and relaxation levels in burn patients. In this pretest-posttest randomized controlled clinical trial, 100 hospitalized burn patients were selected through convenience sampling. Subjects randomly assigned to music and control groups. Data related to demographic and clinical characteristics, analgesics, and physiologic measures were collected by researcher-made tools. Visual analog scale was used to determine pain, anxiety, and relaxation levels before and after the intervention in 3 consecutive days. Patients' preferred music was offered once a day for 3 days. The control group only received routine care. Data were analyzed using SPSS-PC (V. 20.0). According to paired t-test, there were significant differences between mean scores of pain (P < .001), anxiety (P < .001), and relaxation (P < .001) levels before and after intervention in music group. Independent t-test indicated a significant difference between the mean scores of changes in pain, anxiety, and relaxation levels before and after intervention in music and control groups (P < .001). No differences were detected in the mean scores of physiologic measures between groups before and after music intervention. Music is an inexpensive, appropriate, and safe intervention for applying to burn patients with background pain and anxiety at rest. To produce more effective comfort for patients, it is necessary to compare different types and time lengths of music intervention to find the best approach. PMID- 26132049 TI - Video-Enhanced Telemedicine Improves the Care of Acutely Injured Burn Patients in a Rural State. AB - The acute care of burn patients is critical and can be a daunting experience for emergency personnel because of the scarcity of burn injuries. Telemedicine that incorporates a visual component can provide immediate expertise in the treatment and management of these injuries. The authors sought to evaluate the addition of video telemedicine to our current telephone burn transfer program. During a 2 year period, 282 patients, 59.4% of all burn patients transferred from outside hospitals, were enrolled in the study. In addition to the scripted call with the charge nurse (ChargeRN) and the accepting physician, nine hospitals also transmitted video images of the wounds before transfer as part of a store and forward telemedicine transfer program (77, 27.6%). The accuracy of burn size estimations (BSA burned) and management changes (fluid requirements, transfer mode, and final disposition) were analyzed between the telephones-only sites (T only) and the video-enhanced sites. Referringstaff participating in video enhanced telemedicine were sent a Google survey assessing their experience the following day. The referring staff (Referringstaff) was correct in their burn assessment 20% of the time. Video assessment improved the ChargeRN BSA burned and resulted in more accurate fluid resuscitation (P = .030), changes in both transportation mode (P = .042), and disposition decisions (P = .20). The majority of the Referringstaff found that video-enhanced telemedicine helped them communicate with the burn staff more effectively (3.4 +/- 0.37, scale 1-4). This study reports the successful implementation of video-enhanced telemedicine pilot project in a rural state. Video-enhanced telemedicine using a store and forward process improved burn size estimation and facilitated management changes. Although not quantitatively assessed, the low cost of the system coupled with the changes in transportation and disposition strongly suggests a decrease in healthcare costs associated with the addition of video to a telephone-only transfer program. PMID- 26132051 TI - The Role of a Burn Research Coordinator: A Guide for Novice Coordinators. AB - As health-care complexity and costs increase, evidence-based research has become essential to the advancement of burn care. Multicenter trials involve procedures, regulations, and guidelines that require meticulous attention to details and strict adherence to compliance issues. Taking on a large, multicenter trial can be a daunting task for a new burn research coordinator. The purpose of this article is to provide a resource for new burn research coordinators in multicenter clinical trial planning, especially in the field of burns. The burn research coordinator must possess organizational and multitasking skills, attention to detail, professionalism, initiative, and motivation. The burn research coordinator must exercise five principles of practice: compliance, confidentiality, consistency and correctness, and collaboration. Compliance assures subject safety, study integrity, and burn center reputation. Confidentiality is essential, especially when handling sensitive health information. Maintaining subject privacy through secure links and destruction of linked data in a timely matter protects the subjects and complies with the regulations of many governing bodies. Consistency and correctness minimize human errors through continuous data validation and self-auditing and peer auditing. Collaboration between the Principal Investigator/burn research coordinator and all departments involved in the study maintains the study focus and allows for enforcement of procedures. Preparing a budget confirms adequate compensation for work done by the research team and can be broken down into the following five steps: protocol review, calculation of initial payment, establishment of indirect costs, calculation of direct costs, and budget negotiation. Over time, one becomes familiar with the details involved with study success. Advocating for subject safety and protocol adherence are of highest priority. Study design is the most important element that dictates the success of the study. Anticipating the direct and indirect costs of a particular trial assures that the study can be completed with adequate allotment for staff time, laboratory costs, and supplies. Regular communication with the Principal Investigator, clinical staff, and consultants is vital for study completion. An essential contributor to burn research and the advancement of burn care, the burn research coordinator must balance many study-related tasks. Through the practice of compliance, confidentiality, and organization/planning, the burn research coordinator can ensure proper study management. These recommendations may assist new burn research coordinators in their practice. PMID- 26132050 TI - Hot Beverage Scalds in Australian Children: Still Simmering 10 Years On. AB - The objectives of this study are to describe the proportion, mechanism, severity, and outcomes of hot beverage scald injuries in children presenting at a major burns centre in 2013 and to compare these results with data collected at the same centre 10 years before. A cross-sectional trend analysis was performed to determine the differences in proportion, mechanism, severity, and outcomes of hot beverage scalds in 0-year to 14-year old children presenting to the Stuart Pegg Paediatric Burns Centre, Royal Children's Hospital, Brisbane, Australia, between January 1 and December 31, 2013 and compare these data to presentations at the same burns centre between 1999 and 2002. Of the 759 children treated for burns and scald injuries at Stuart Pegg Paediatric Burns Centre in 2013, 133 (18%) were caused by hot beverages. Although there has been no change in the proportion, injury mechanism or age groups affected in the past 10 years, there has been a significant change in the number of children being admitted to hospital (52% vs 11% in 2013, P < .001), requiring split skin grafts (18% vs 5% in 2013, P < .05), and long-term scar management (26% vs 11% in 2013, P < .05). The decrease in admissions, skin grafts, and scar management requirements can be attributed to several factors; moving from silver sulfadiazine to silver-impregnated dressings at SPBBC from 2003, changes in excision and skin grafting practices, modified referral patterns, a move to non-inpatient care for minor burns, and the increased application of first aid. However, what has not changed is hot beverage scalds remain the leading cause of childhood burns making it a major pediatric public health issue. PMID- 26132052 TI - Porous alpha-MoO3/MWCNT nanocomposite synthesized via a surfactant-assisted solvothermal route as a lithium-ion-battery high-capacity anode material with excellent rate capability and cyclability. AB - A high-performance alpha-MoO3/multiwalled carbon nanotube (MWCNT) nanocomposite material is synthesized via a novel surfactant-assisted solvothermal process followed by low-temperature calcination. Its structure, composition, and morphology are characterized by X-ray diffraction, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, carbon element analysis, nitrogen adsorption-desorption determination, scanning electron microscopy, and transmission electron microscopy techniques. Its electrochemical performance as a high-capacity lithium-ion-battery anode material is investigated by cyclic voltammetry, electrochemical impedance spectroscopy, and galvanostatic discharge/recharge methods. This composite material exhibits not only high capacity but also excellent rate capability and cyclability. For example, when the discharge/charge current density is increased from 0.1 to 2 A g(-1), the reversible charge capacity is only decreased from 1138.3 to 941.4 mAh g(-1), giving a capacity retention of 82.7%. Even if it is cycled at a high current density of 20 A g(-1), a reversible charge capacity of 490.2 mAh g(-1) is still retained, showing a capacity retention of 43.1%. When it is repeatedly cycled at a current of 0.5 A g(-1), the initial reversible charge capacity is 1041.1 mAh g( 1). A maximum charge capacity of 1392.2 mAh g(-1) is achieved at the 292th cycle. After 300 cycles, a high charge capacity of 1350.3 mAh g(-1) is maintained. Enhancement of the electrical conduction contributed by the MWCNT composite component as well as the loose and porous texture of the MoO3/MWCNT composite is suggested to be responsible for the excellent performance. PMID- 26132047 TI - Postburn Hypermetabolism: Past, Present, and Future. AB - Hypermetabolism is the ubiquitous response to a severe burn injury, which was first described in the nineteenth century. Despite identification of important components of this complex response, hypermetabolism is still not well understood in its entirety. This article describes this incredibly fascinating response and the understanding we have gained over the past 100 years. Additionally, this article describes novel insights and delineates treatment options to modulate postburn hypermetabolism with the goal to improve outcomes of burn patients. PMID- 26132053 TI - Climate change, health and infectious disease. PMID- 26132054 TI - How to Retain the Trust of Patients and Families When We Will Not Provide the Treatment They Want. AB - How might clinicians best try to retain the trust of patients and family members after clinicians oppose giving a treatment? If clinicians can maintain the trust of patients and families in these situations, this may soften what may be the greatest possible loss--the death of a loved one. I discuss what clinicians seeking to retain trust should not do--namely impose their values and reason wrongly--and introduce strategies that clinicians may use to reduce both. I present five principles that clinicians can follow to try to retain trust, with examples that illustrate each. I suggest specific interventions that clinicians can make, especially when they anticipate that a patient and/or family may, in time, want a treatment that is futile. PMID- 26132055 TI - A Justifiable Asymmetry. AB - It is a clinician's cliche that a physician only challenges a patient's capacity to make a treatment decision if that decision is not what the physician wants. Agreement is proof of decisional capacity; disagreement is proof or at least evidence of capacity's absence. It is assumed that this asymmetry cannot be justified, that the asymmetry must be a form of physicians' paternalism. Instead what is at issue when patient and physician disagree are usually two laudable impulses. The first is physicians' commitment to patients' well-being: physicians have a professional obligation as well as, ideally, a personal commitment to take care of patients--to do their best to bring about a positive medical outcome. The second impulse is common to much of human life, namely, the urge to find and to understand the source of our disagreements with one another. In this article we argue that, jointly, these impulses justify the asymmetry with regard to examining patients' capacity. PMID- 26132056 TI - Not Taking "Yes" for an Answer. AB - Does the practice of questioning the decision-making capacity of patients who disagree with recommended medical interventions amount to paternalism on the part of physicians who would not have raised questions about competence had these patients accepted the recommendation? Brudney and Siegler provide a nuanced argument why the practice can be both pragmatically and ethically justifiable, particularly if physicians follow a "decision tree" that they recommend for cases where disagreements occur. Nonetheless, the history of this subject shows that bioethicists have long been worried that the "outcome approach" (challenging patient's capacity because of substantive disagreements with their choices) undermines respect for autonomy, and the more refined version from Brudney and Siegler still creates some further concerns about the resulting inadequacies in communication and comprehension in the physician-patient relationship. PMID- 26132057 TI - Moral Reasoning among HEC Members: An Empirical Evaluation of the Relationship of Theory and Practice in Clinical Ethics Consultation. AB - In light of the ongoing development and implementation of core competencies in bioethics, it is important to proceed with a clear sense of how bioethics knowledge is utilized in the functioning of hospital ethics committees (HECs). Without such an understanding, we risk building a costly edifice on a foundation that is ambiguous at best. This article examines the empirical relationship between traditional paradigms of bioethics theory and actual decision making by HEC members using survey data from HEC members. The assumption underlying the standardization of qualifications and corresponding call for increased education of HEC members is that they will base imminent case decisions on inculcated knowledge. Our data suggest, however, that HEC members first decide intuitively and then look for justification, thereby highlighting the need to re-examine the pedagogical processes of ethics education in the process of standardizing and improving competencies. PMID- 26132058 TI - Reasoning Backwards by Design: Commentary on "Moral Reasoning among HEC Members". AB - Empirical assessment of the practice of clinical ethics is made difficult by the limited standardization of settings, structures, processes, roles, and training for ethics consultation, as well as by whether individual ethics consultants or hospital ethics committees (HECs) provide consultation. Efforts to study the relationship between theory and practice in the work of HECs likewise require the spelling out of assumptions and definition of key variables, based in knowledge of the core concepts of clinical ethics and logistics of clinical consultation. The survey of HEC members reported by Wasserman and colleagues illustrates the difficulty of such research and calls attention to need for studies of real-time, complex decision making to inform conclusions about how theory affects practice. PMID- 26132059 TI - Expanding the Use of Continuous Sedation Until Death: Moving Beyond the Last Resort for the Terminally Ill. AB - As currently practiced, the use of continuous sedation until death (CSD) is controlled by clinicians in a way that may deny patients a key choice in controlling their dying process. Ethical guidelines from the American Medical Association and the American Academy of Pain Medicine describe CSD as a "last resort," and a position statement from the American Academy of Hospice and Palliative Medicine describe it as "an intervention reserved for extreme situations." Accordingly, patients must progress to unremitting pain and suffering and reach a last-resort stage before the option to pursue CSD is considered. Alternatively, we present and defend a new guideline in which decisionally capable, terminally ill patients who have a life expectancy of less than six months may request CSD before being subjected to the refractory suffering of a treatment of "last resort." PMID- 26132060 TI - Continuous Sedation Until Death Should Not Be an Option of First Resort. AB - Samuel H. LiPuma and Joseph P. DeMarco argue for a positive right to continuous sedation until death (CSD) for any patient with a life expectancy less than six months. They reject any requirement of proportionality. Their proposed guideline makes CSD an option for a decisional adult patient with an appropriate terminal diagnosis regardless of whether suffering (physical or existential) is present. This guideline purports to "empower" the patient with the ability to control the timing and manner of her death. This extends even to the option to "opt out" of the awareness and experience of dying and to avoid suffering altogether, even if one's symptoms and suffering could be effectively treated. We respond first with a critique of their terminology. We then turn to some purely practical considerations of how this guideline might be enacted in the current atmosphere of American hospice and palliative care medicine. We close with a consideration of one philosophical concern that might ground the discussion of risks, benefits, and alternatives necessary for informed consent. PMID- 26132061 TI - "Let Me Keep My Dead Husband's Sperm": Ethical Issues in Posthumous Reproduction. AB - The feasibility of posthumous reproduction when the surviving partner is female has brought to light many ethical, moral, social, and legal issues. This review aims to summarize these issues and to assist clinicians who may be faced with such requests. A question list, used for health technologies assessment, was utilized in a question-answer approach as the review methodology. Of the 1,208 publications identified through a comprehensive literature search in biomedical, psychological, and ethical databases, 31 articles included arguments related to one or more questions from the predefined question set. Key stakeholders identified include the deceased, the requesting party, the resultant child, the physician, and society. Key ethical issues relevant to posthumous reproduction include the four traditional pillars of medical ethics--autonomy, beneficence, nonmaleficence, justice--as well as the stakeholders' rights and sociocultural attitudes. The ethical framework formulated by these issues has been incorporated in a clinical ethics decision-making tool that could prove useful to clinicians and decision makers. PMID- 26132062 TI - The Value of Virginity. AB - Hymen reconstruction surgery is a simple procedure to repair a woman's hymen, requested by women who, for religious and cultural reasons, believe they must appear to have an intact hymen on their wedding night. Debates surrounding possible ethical justification for the procedure are complex and heated. These articles from the Harvard Ethics Consortium present and explore the case of a young woman who asked a young female physician on call for a referral for the procedure. PMID- 26132063 TI - When Bleeding Is Vital: Surgically Ensuring the "Virginal" State. AB - A young woman called me to ask for a referral to a physician who provided hymen reconstruction surgery. She had had premarital intercourse and came from a cultural background in which it was very important to "prove virginity" on the wedding night. This article deals with my internal struggle whether or not to provide the referral. I felt that providing it would have made me complicit in supporting gender inequality, as men are not required to "prove virginity" to get married. At the same time, I was concerned about the repercussions of not being able to "prove virginity" would have on the caller. I had no explicit guidance on what to do in such a situation--it was not covered by the professional responsibilities I had as a research assistant. PMID- 26132064 TI - A Hymen Epiphany. AB - The hymen is a structure of the female genitalia that is poorly understood even by many medical professionals. Despite the significant anatomical variation in the hymen and no guarantee that rupture or bleeding will occur at first coitus, it has come to hold major cultural significance around the world as a perceived biological indicator of virginity. The persistence of such myths around the hymen causes real harm, including the increase in so-called revirgination surgical procedures. PMID- 26132065 TI - On Hymenoplasty. AB - Some traditional cultural practices assure expected wedding night bleeding, to help preserve the honor of all parties. PMID- 26132066 TI - Hymen Restoration: "My" Discomfort, "Their" Culture, and Women's Missing Voice. AB - The discourse among medical and scientific communities on hymen restoration is largely missing the voice of women affected. This article calls for a more nuanced reflection on women's real life experiences and the complexities inherent in the negotiation process about the surgery going beyond "ideologies" and the extremes of rape and threats to life. By taking the clinical experience of a woman who requests restoration surgery before her arranged marriage, this article illuminates the grey zone beyond these extremes and explores an individual woman's options for making her own choices. PMID- 26132067 TI - The Value of Virginity and the Value of the Law: Accommodating Multiculturalism. AB - Hymenoplasty is a minor surgical procedure requested by women who, for cultural or religious reasons, need to remain a virgin until marriage. In this article I assess whether the public healthcare system of a liberal state should provide it as part of a policy of multicultural accommodation. I conclude that, in order to remain loyal to certain ethical ideals linked to the rule of law, liberal states should give access to hymenoplasty only to women for whom premarital virginity is a precondition for their flourishing within their community and who say they are victims of sexual assault. PMID- 26132068 TI - Is Hymenoplasty Anti-Feminist? AB - Hymenoplasty is a practice that must be judged from within its cultural confines and not only from outside. It offers women who have grown up within the sexual norms of a Western society the chance to return to their parental culture, with its female-specific virginity expectations. Hymenoplasty allows women to be sexually active prior to marriage, which equalizes the discrepancy between gender norms on premarital sexual experience. Caution is needed when comparing hymenoplasty to female genital mutilation. However, comparing hymenoplasty to other cosmetic genital modification procedures raises unique ethical, social, and medical quandaries that highlight the importance of patient's autonomy. PMID- 26132069 TI - Doctoring the Genitals: Towards Broadening the Meaning of Social Medicine. AB - Doctoring the genitals is compatible with a recognizable conception of social medicine. This commentary critically examines the distinction between medical and nonmedical procedures; presents an alternative account of Sohaila Bastami's personal reaction to the anonymous caller's request for referral information concerning hymen reconstruction surgery; and makes use of Yelp to simulate the caller's procedure for locating a helpful practitioner. Yelp is a very useful informational search engine that does not subject its users to a moral examination. PMID- 26132070 TI - Legal Briefing: Adult Orphans and the Unbefriended: Making Medical Decisions for Unrepresented Patients without Surrogates. AB - This issue's "Legal Briefing" column covers recent legal developments involving medical decision making for incapacitated patients who have no available legally authorized surrogate decision maker. These individuals are frequently referred to either as "adult orphans" or as "unbefriended," "isolated," or "unrepresented" patients. The challenges involved in obtaining consent for medical treatment on behalf of these individuals have been the subject of major policy reports. Indeed, caring for the unbefriended has even been described as the "single greatest category of problems" encountered in bioethics consultation. In 2012, JCE published a comprehensive review of the available mechanisms by which to make medical decisions for the unbefriended. The purpose of this "Legal Briefing" is to update the 2012 study. Accordingly, this "Legal Briefing" collects and describes significant legal developments from only the past three years. My basic assessment has not changed. "Existing mechanisms to address the issue of decision making for the unbefriended are scant and not uniform." Most facilities are "muddling through on an ad hoc basis." But the situation is not wholly negative. There have been a number of promising new initiatives. I group these developments into the following seven categories: 1. Increased Attention and Discussion 2. Prevention through Better Advance Care Planning 3. Prevention through Expanded Default Surrogate Lists 4. Statutorily Authorized Intramural Mechanisms 5. California Litigation Challenging the Team Approach 6. Public Guardianship 7. Improving Existing Guardianship Processes. PMID- 26132071 TI - Letter: Possible Unintended Consequences of Including Equal-Priority Surrogates. PMID- 26132072 TI - Letter: Response to Perry and Venkat. PMID- 26132073 TI - In-Depth Transcriptome Sequencing of Mexican Lime Trees Infected with Candidatus Phytoplasma aurantifolia. AB - Witches' broom disease of acid lime greatly affects the production of Mexican lime in Iran. It is caused by a phytoplasma (Candidatus Phytoplasma aurantifolia). However, the molecular mechanisms that underlie phytoplasma pathogenicity and the mode of interactions with host plants are largely unknown. Here, high-throughput transcriptome sequencing was conducted to explore gene expression signatures associated with phytoplasma infection in Mexican lime trees. We assembled 78,185 unique transcript sequences (unigenes) with an average length of 530 nt. Of these, 41,805 (53.4%) were annotated against the NCBI non redundant (nr) protein database using a BLASTx search (e-value <= 1e-5). When the abundances of unigenes in healthy and infected plants were compared, 2,805 transcripts showed significant differences (false discovery rate <= 0.001 and log2 ratio >= 1.5). These differentially expressed genes (DEGs) were significantly enriched in 43 KEGG metabolic and regulatory pathways. The up regulated DEGs were mainly categorized into pathways with possible implication in plant-pathogen interaction, including cell wall biogenesis and degradation, sucrose metabolism, secondary metabolism, hormone biosynthesis and signalling, amino acid and lipid metabolism, while down-regulated DEGs were predominantly enriched in ubiquitin proteolysis and oxidative phosphorylation pathways. Our analysis provides novel insight into the molecular pathways that are deregulated during the host-pathogen interaction in Mexican lime trees infected by phytoplasma. The findings can be valuable for unravelling the molecular mechanisms of plant-phytoplasma interactions and can pave the way for engineering lime trees with resistance to witches' broom disease. PMID- 26132074 TI - PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice. AB - 64Cu radiolabelled nanodiscs based on the 11 alpha-helix MSP1E3D1 protein and 1 palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid protein particle while fully conserving the particle structure including the amphipathic protein fold. PMID- 26132076 TI - Electronic Energy Levels and Band Alignment for Aqueous Phenol and Phenolate from First Principles. AB - Electronic energy levels in phenol and phenolate solutions have been computed using density functional theory and many-body perturbation theory. The valence and conduction bands of the solvent and the ionization energies of the solutes have been aligned with respect to the vacuum level based on the concept of a computational standard hydrogen electrode. We have found significant quantitative differences between the generalized-gradient approximation, calculations with the HSE hybrid functional, and many-body perturbation theory in the G0W0 approximation. For phenol, two ionization energies below the photoionization threshold of bulk water have been assigned in the spectrum of Kohn-Sham eigenvalues of the solution. Deprotonation to phenolate was found to lift a third occupied energy level above the valence band maximum of the solvent which is characterized by an electronic lone pair at the hydroxyl group. The second and third ionization energies of phenolate were found to be very similar and explain the intensity pattern observed in recent experiments using liquid-microjet photoemission spectroscopy. PMID- 26132075 TI - New Indole Tubulin Assembly Inhibitors Cause Stable Arrest of Mitotic Progression, Enhanced Stimulation of Natural Killer Cell Cytotoxic Activity, and Repression of Hedgehog-Dependent Cancer. AB - We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of the indole and with halogen or methoxy substituent(s) at positions 4-7. Compounds 33 and 44 strongly inhibited the growth of the P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES and Messa/Dx5. At 10 nM, 33 and 44 stimulated the cytotoxic activity of NK cells. At 20-50 nM, 33 and 44 arrested >80% of HeLa cells in the G2/M phase of the cell cycle, with stable arrest of mitotic progression. Cell cycle arrest was followed by cell death. Indoles 33, 44, and 81 showed strong inhibition of the SAG-induced Hedgehog signaling activation in NIH3T3 Shh-Light II cells with IC50 values of 19, 72, and 38 nM, respectively. Compounds of this class potently inhibited tubulin polymerization and cancer cell growth, including stimulation of natural killer cell cytotoxic activity and repression of Hedgehog-dependent cancer. PMID- 26132077 TI - Thriving in the Cold: Glacial Expansion and Post-Glacial Contraction of a Temperate Terrestrial Salamander (Plethodon serratus). AB - The dynamic geologic history of the southeastern United States has played a major role in shaping the geographic distributions of amphibians in the region. In the phylogeographic literature, the predominant pattern of distribution shifts through time of temperate species is one of contraction during glacial maxima and persistence in refugia. However, the diverse biology and ecology of amphibian species suggest that a "one-size-fits-all" model may be inappropriate. Nearly 10% of amphibian species in the region have a current distribution comprised of multiple disjunct, restricted areas that resemble the shape of Pleistocene refugia identified for other temperate taxa in the literature. Here, we apply genetics and spatially explicit climate analyses to test the hypothesis that the disjunct regions of these species ranges are climatic refugia for species that were more broadly distributed during glacial maxima. We use the salamander Plethodon serratus as a model, as its range consists of four disjunct regions in the Southeast. Phylogenetic results show that P. serratus is comprised of multiple genetic lineages, and the four regions are not reciprocally monophyletic. The Appalachian salamanders form a clade sister to all other P. serratus. Niche and paleodistribution modeling results suggest that P. serratus expanded from the Appalachians during the cooler Last Glacial Maximum and has since been restricted to its current disjunct distribution by a warming climate. These data reject the universal applicability of the glacial contraction model to temperate taxa and reiterate the importance of considering the natural history of individual species. PMID- 26132078 TI - Effects of Infant Pneumococcal Conjugate Vaccination on Serotype Distribution in Invasive Pneumococcal Disease among Children and Adults in Germany. AB - This study describes the effects of the introduction of universal infant pneumococcal conjugate vaccination in 2006 on invasive pneumococcal disease (IPD) among children and adults in Germany with a focus on the dynamics of serotype distribution in vaccinated and non-vaccinated age groups. Over a period of 22 years (1992-2014), microbiological diagnostic laboratories from all over Germany have been sending isolates of IPD cases to the German National Reference Center for Streptococci on a voluntary basis. Streptococcus pneumoniae isolates were serotyped using Neufeld's Quellung method. Among children <16 years, the proportion of PCV7 serotypes among isolates from IPD cases decreased from 61.8% before vaccination (1997-2006) to 23.5% in the early vaccination period (2007 2010; p = 1.30E-72) and sank further to 5.2% in the late vaccination period (2010 2014; p = 4.59E-25). Similar reductions were seen for the separate age groups <2 years, 2-4 years and 5-15 years. Among adults, the proportion of PCV7 serotypes decreased from 43.4% in the pre-vaccination period (1992-2006) to 24.7% (p = 3.78E-88) in the early vaccination period and 8.2% (p = 5.97E-161) in the late vaccination period. Both among children and among adults, the non-PCV7 serotypes 1, 3, 7F and 19A significantly increased in the early vaccination period. After the switch from PCV7 to PVC10/PCV13 for infant vaccination in 2010, serotypes 1, 6A and 7F significantly decreased. A decrease in serotype 19A was only observed in 2013-2014, as compared to 2010-2011 (children p = 4.16E-04, adults p = 6.98E 06). Among adults, serotype 3, which strongly increased in the early vaccination period (p = 4.44E-15), remained at a constant proportion in the late vaccination period. The proportion of non-PCV13 vaccine serotypes increased over the whole vaccination period, with serotypes 10A, 12F, 23B, 24F and 38 most significantly increasing among children and serotypes 6C, 12F, 15A, 22F and 23B increasing among adults. Eight years of childhood pneumococcal conjugate vaccination have had a strong effect on the pneumococcal population in Germany, both among the target group for vaccination as well as among older children and adults. PMID- 26132079 TI - CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study. AB - PURPOSE: Genetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD). We investigated whether genotype could influence response to docosahexaenoic acid (DHA)-supplementation in the occurrence of choroidal new vessels (CNV). METHODS: The Nutritional AMD Treatment 2 (NAT2) study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo. RESULTS: Patients carrying the risk allele (C) for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR)=0.97; 95% Confidence Interval (CI): 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous). Patients carrying the risk allele (T) for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12) for heterozygous and HR=1.78; 95%CI: 0.90 3.52 for homozygous). A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01). We showed a protective effect of DHA supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008). CONCLUSIONS: These results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation. TRIAL REGISTRATION: ISRCTN registry 98246501. PMID- 26132080 TI - A Probabilistic Analysis of Sparse Coded Feature Pooling and Its Application for Image Retrieval. AB - Feature coding and pooling as a key component of image retrieval have been widely studied over the past several years. Recently sparse coding with max-pooling is regarded as the state-of-the-art for image classification. However there is no comprehensive study concerning the application of sparse coding for image retrieval. In this paper, we first analyze the effects of different sampling strategies for image retrieval, then we discuss feature pooling strategies on image retrieval performance with a probabilistic explanation in the context of sparse coding framework, and propose a modified sum pooling procedure which can improve the retrieval accuracy significantly. Further we apply sparse coding method to aggregate multiple types of features for large-scale image retrieval. Extensive experiments on commonly-used evaluation datasets demonstrate that our final compact image representation improves the retrieval accuracy significantly. PMID- 26132081 TI - Sequence Conservation, Radial Distance and Packing Density in Spherical Viral Capsids. AB - The conservation level of a residue is a useful measure about the importance of that residue in protein structure and function. Much information about sequence conservation comes from aligning homologous sequences. Profiles showing the variation of the conservation level along the sequence are usually interpreted in evolutionary terms and dictated by site similarities of a proper set of homologous sequences. Here, we report that, of the viral icosahedral capsids, the sequence conservation profile can be determined by variations in the distances between residues and the centroid of the capsid - with a direct inverse proportionality between the conservation level and the centroid distance - as well as by the spatial variations in local packing density. Examining both the centroid and the packing density models against a dataset of 51 crystal structures of nonhomologous icosahedral capsids, we found that many global patterns and minor features derived from the viral structures are consistent with those present in the sequence conservation profiles. The quantitative link between the level of conservation and structural features like centroid-distance or packing density allows us to look at residue conservation from a structural viewpoint as well as from an evolutionary viewpoint. PMID- 26132083 TI - Spatially Estimating Disturbance of Harbor Seals (Phoca vitulina). AB - Tidewater glacial fjords in Alaska provide habitat for some of the largest aggregations of harbor seals (Phoca vitulina), with calved ice serving as platforms for birthing and nursing pups, molting, and resting. These fjords have also been popular destinations for tour ships for more than a century, with dramatic increases in vessel traffic since the 1980s. Seals on ice are known to flush into the water when approached by tour ships, but estimating the exposure to disturbance across populations is difficult. Using aerial transect sampling while simultaneously tracking vessel movements, we estimated the spatial overlap between seals on ice and cruise ships in Disenchantment Bay, Alaska, USA. By integrating previously estimated rates of disturbance as a function of distance with an 'intensity surface' modeled spatially from seal locations in the surveys, we calculated probabilities of seals flushing during three separate ship visits. By combining our estimate of seals flushed with a modeled estimate of the total fjord population, we predict that up to 14% of the seals (up to 11% of pups) hauled out would have flushed into the water, depending on the route taken by ships relative to seal aggregations. Such high potential for broad-scale disturbance by single vessels (when up to 4 ships visit per day) was unexpected and underscores the need to 1) better understand long-term effects of disturbance; 2) regularly monitor populations exposed to high vessel traffic; and 3) develop conservation measures to reduce seal-ship overlap. PMID- 26132082 TI - Enhancement of Apoptosis by Titanium Alloy Internal Fixations during Microwave Treatments for Fractures: An Animal Study. AB - OBJECTIVE: Microwaves are used in one method of physical therapy and can increase muscle tissue temperature which is useful for improving muscle, tendon and bone injuries. In the study, we sought to determine whether titanium alloy internal fixations influence apoptosis in tissues subjected to microwave treatments at 2,450 MHz and 40 W during the healing of fractures because this issue is not yet fully understood. METHODS: In this study, titanium alloy internal fixations were used to treat 3.0-mm transverse osteotomies in the middle of New Zealand rabbits' femurs. After the operation, 30-day microwave treatments were applied to the 3.0 mm transverse osteotomies 3 days after the operation. The changes in the temperatures of the muscle tissues in front of the implants or the 3.0 mm transverse osteotomies were measured during the microwave treatments. To characterize the effects of titanium alloy internal fixations on apoptosis in the muscles after microwave treatment, we performed TUNEL assays, fluorescent real time (quantitative) PCR, western blotting analyses, reactive oxygen species (ROS) detection and transmission electron microscopy examinations. RESULTS: The temperatures were markedly increased in the animals with the titanium alloy implants. Apoptosis in the muscle cells of the implanted group was significantly more extensive than that in the non-implanted control group at different time points. Transmission electron microscopy examinations of the skeletal muscles of the implanted groups revealed muscular mitochondrial swelling, vacuolization. ROS, Bax and Hsp70 were up-regulated, and Bcl-2 was down-regulated in the implanted group. CONCLUSION: Our results suggest that titanium alloy internal fixations caused greater muscular tissue cell apoptosis following 2,450 MHz, 40 W microwave treatments in this rabbit femur fracture models. PMID- 26132085 TI - Are we burying our heads in the sand? Preventing small bowel obstruction from the V-loc(r) suture in laparoscopic ventral rectopexy. AB - AIM: There have been increasing reports in the literature highlighting the complication of V-loc(r) associated small bowel obstruction in patients after laparoscopic ventral rectopexy. METHODS AND RESULTS: Using clinical and experimental evidence, we demonstrate that bowel obstruction from the V-loc(r) following laparoscopic ventral rectopexy will still occur despite the technical recommendations to bury or cut its barbed end flush. CONCLUSION: The risk of bowel obstruction from the V-loc(r) following laparoscopic ventral rectopexy is not negated by burying or cutting its barbed end flush. We have proposed its pathogenesis to refute commonly held assumptions about its prevention. PMID- 26132084 TI - Cooperation between Paxillin-like Protein Pxl1 and Glucan Synthase Bgs1 Is Essential for Actomyosin Ring Stability and Septum Formation in Fission Yeast. AB - In fungal cells cytokinesis requires coordinated closure of a contractile actomyosin ring (CAR) and synthesis of a special cell wall structure known as the division septum. Many CAR proteins have been identified and characterized, but how these molecules interact with the septum synthesis enzymes to form the septum remains unclear. Our genetic study using fission yeast shows that cooperation between the paxillin homolog Pxl1, required for ring integrity, and Bgs1, the enzyme responsible for linear beta(1,3)glucan synthesis and primary septum formation, is required for stable anchorage of the CAR to the plasma membrane before septation onset, and for cleavage furrow formation. Thus, lack of Pxl1 in combination with Bgs1 depletion, causes failure of ring contraction and lateral cell wall overgrowth towards the cell lumen without septum formation. We also describe here that Pxl1 concentration at the CAR increases during cytokinesis and that this increase depends on the SH3 domain of the F-BAR protein Cdc15. In consequence, Bgs1 depletion in cells carrying a cdc15DeltaSH3 allele causes ring disassembly and septation blockage, as it does in cells lacking Pxl1. On the other hand, the absence of Pxl1 is lethal when Cdc15 function is affected, generating a large sliding of the CAR with deposition of septum wall material along the cell cortex, and suggesting additional functions for both Pxl1 and Cdc15 proteins. In conclusion, our findings indicate that CAR anchorage to the plasma membrane through Cdc15 and Pxl1, and concomitant Bgs1 activity, are necessary for CAR maintenance and septum formation in fission yeast. PMID- 26132087 TI - Making sense of HIV stigma: Representations in young Africans' HIV-related narratives. AB - In addition to undermining the quality of life of those infected and affected by HIV, HIV-related stigma impedes access to prevention and treatment services, thereby threatening to erode the promise of recent advances in these areas. This paper provides insights into the socio-contextual and sense-making processes that inform HIV stigma through an innovative form of empirical data: creative fictional narratives written by young Africans (aged 10-24) for an HIV-themed scriptwriting competition. From a sample of 586 narratives from six sub-Saharan countries, we selected for illustrative purposes three on account of the complexity of their representation of HIV stigma. We conducted a close reading of each, using stigma theory as a lens. Through their explicit accounts of stigmatising attitudes and behaviours of characters and through implicit contradictions, tensions and ambivalence in their messaging, the narratives provide insights into the symbolic and social processes that create and sustain HIV stigma. Our analysis illuminates the authors' struggles to navigate the cultural resources available to them in their efforts to make sense of HIV, gender and sexuality. It highlights some limitations of current communication efforts and the potential for narrative-based communication approaches to engage with representations that devalue women and people living with HIV. PMID- 26132088 TI - Dehydrogenative coupling involving P(O)-H bonds: a powerful way for the preparation of phosphoryl compounds. AB - Because of the unique properties and wide applications, continuing efforts have been devoted to developing simpler and cleaner methods for the synthesis of organophosphorus compounds. Recently, transition metal-catalysed dehydrogenative coupling has been emerging as one of the powerful methodologies for constructing chemical bonds. Herein, we highlight the recent progress in the preparation of organophosphorus compounds via transition metal-catalysed dehydrogenative couplings of P(O)H compounds with Z-H compounds. PMID- 26132089 TI - A Complex Presentation of Pediatric Neuroleptic Malignant Syndrome Related to Polypharmacy in a 12-Year-Old Male. PMID- 26132090 TI - The Effect of Alpinia zerumbet Essential Oil on Post-Stroke Muscle Spasticity. AB - The essential oil of Alpinia zerumbet (EOAz) presents myorelaxant and antispasmodic actions on cardiac and smooth muscles. The aim of this study was to investigate the effect of EOAz on the skeletal muscle contraction in post-stroke spasticity. Fifteen adults with unilateral hemiparesis and spasticity resulting from stroke were submitted to surface electromyography readings of the gastrocnemius muscle, before and after 10 daily applications (dermal 0.05 mL per muscle belly) of EOAz. The healthy contralateral muscles without applying the oil were used as controls. The analysis showed that, in both lateral and medial gastrocnemius, the values of all studied variables (root mean square, maximum amplitude and median power frequency) were significantly decreased in pathological legs during muscle contraction (Wilcoxon test, p < 0.05). Moreover, spastic muscles presented different results before and after dermal application of EOAz: The mean values of root mean square and median power frequency were significantly increased in lateral and medial gastrocnemius, and also, the maximum amplitude increased in medial gastrocnemius (Mann-Whitney test, p < 0.05). The results suggest that EOAz acts in the skeletal spastic muscle contraction by promoting relaxation and improvement of the muscular performance. Thus, the EOAz can be useful for the clinical management of secondary effects in patients with cerebral vascular disease. PMID- 26132091 TI - Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies. AB - Pancreatic ductal adenocarcinoma (PDAC) contains a subset of exclusively tumorigenic cancer stem cells (CSCs) which have been shown to drive tumor initiation, metastasis and resistance to radio- and chemotherapy. Here we describe a specific methodology for culturing primary human pancreatic CSCs as tumor spheres in anchorage-independent conditions. Cells are grown in serum-free, non-adherent conditions in order to enrich for CSCs while their more differentiated progenies do not survive and proliferate during the initial phase following seeding of single cells. This assay can be used to estimate the percentage of CSCs present in a population of tumor cells. Both size (which can range from 35 to 250 micrometers) and number of tumor spheres formed represents CSC activity harbored in either bulk populations of cultured cancer cells or freshly harvested and digested tumors. Using this assay, we recently found that metformin selectively ablates pancreatic CSCs; a finding that was subsequently further corroborated by demonstrating diminished expression of pluripotency associated genes/surface markers and reduced in vivo tumorigenicity of metformin treated cells. As the final step for preclinical development we treated mice bearing established tumors with metformin and found significantly prolonged survival. Clinical studies testing the use of metformin in patients with PDAC are currently underway (e.g., NCT01210911, NCT01167738, and NCT01488552). Mechanistically, we found that metformin induces a fatal energy crisis in CSCs by enhancing reactive oxygen species (ROS) production and reducing mitochondrial transmembrane potential. In contrast, non-CSCs were not eliminated by metformin treatment, but rather underwent reversible cell cycle arrest. Therefore, our study serves as a successful example for the potential of in vitro sphere formation as a screening tool to identify compounds that potentially target CSCs, but this technique will require further in vitro and in vivo validation to eliminate false discoveries. PMID- 26132092 TI - An Underappreciated Cause of Postprandial Abdominal Pain. PMID- 26132093 TI - Essential oil of Lippia alba and its main constituent citral block the excitability of rat sciatic nerves. AB - Lippia alba is empirically used for infusions, teas, macerates, and hydroalcoholic extracts because of its antispasmodic, analgesic, sedative, and anxiolytic effects. Citral is a mixture of trans-geranial and cis-neral and is the main constituent of L. alba essential oil and possesses analgesic, anxiolytic, anticonvulsant, and sedative effects. The present study evaluated the effects of the essential oil of L. alba (EOLa) and citral on compound action potentials (CAPs) in Wistar rat sciatic nerves. Both drugs inhibited CAP in a concentration-dependent manner. The calculated half-maximal inhibitory concentrations (IC50) of peak-to-peak amplitude were 53.2 ug/mL and 35.00 ug/mL (or 230 uM) for EOLa and citral, respectively. Peak-to-peak amplitude of the CAP was significantly reduced by 30 ug/mL EOLa and 10 ug/mL citral. EOLa and citral (at 60 and 30 ug/mL, values close to their respective IC50 for CAP blockade) significantly increased chronaxy and rheobase. The conduction velocity of the first and second CAP components was statistically reduced to ~86% of control with 10 ug/mL EOLa and ~90% of control with 3 ug/mL citral. This study showed that EOLa inhibited nerve excitability and this effect can be explained by the presence of citral in its composition. Both EOLa and citral showed inhibitory actions at lower concentrations compared with other essential oils and constituents with local anesthetic activity. In conclusion, these data demonstrate that EOLa and citral are promising agents in the development of new drugs with local anesthetic activity. PMID- 26132094 TI - Role of a GenoType MTBDRplus line probe assay in early detection of multidrug resistant tuberculosis at a Brazilian reference center. AB - Resistance to Mycobacterium tuberculosis is a reality worldwide, and its diagnosis continues to be difficult and time consuming. To face this challenge, the World Health Organization has recommended the use of rapid molecular tests. We evaluated the routine use (once a week) of a line probe assay (Genotype MTBDRplus) for early diagnosis of resistance and for assessment of the main related risk factors over 2 years. A total of 170 samples were tested: 15 (8.8%) were resistant, and multidrug resistance was detected in 10 (5.9%). The sensitivity profile took 3 weeks (2 weeks for culture and 1 week for rapid testing). Previous treatment for tuberculosis and the persistence of positive acid-fast smears after 4 months of supervised treatment were the major risk factors observed. The use of molecular tests enabled early diagnosis of drug resistant bacilli and led to appropriate treatment of the disease. This information has the potential to interrupt the transmission chain of resistant M. tuberculosis. PMID- 26132095 TI - Relationship between salt consumption measured by 24-h urine collection and blood pressure in the adult population of Vitoria (Brazil). AB - High salt intake is related to an increase in blood pressure and development of hypertension. However, currently, there are no national representative data in Brazil using the gold standard method of 24-h urine collection to measure sodium consumption. This study aimed to determine salt intake based on 24-h urine collection in a sample of 272 adults of both genders and to correlate it with blood pressure levels. We used a rigorous protocol to assure an empty bladder prior to initiating urine collection. We excluded subjects with a urine volume <500 mL, collection period outside of an interval of 23-25 h, and subjects with creatinine excretion that was not within the range of 14.4-33.6 mg/kg (men) and 10.8-25.2 mg/kg (women). The mean salt intake was 10.4+/-4.1 g/day (d), and 94% of the participants (98% of men and 90% of women) ingested more than the recommended level of 5 g/d. We found a positive association between salt and body mass index (BMI) categories, as well as with salt and blood pressure, independent of age and BMI. The difference in systolic blood pressure reached 13 mmHg between subjects consuming less than 6 g/d of salt and those ingesting more than 18 g/d. Subjects with hypertension had a higher estimated salt intake than normotensive subjects (11.4+/-5.0 vs 9.8+/-3.6 g/d, P<0.01), regardless of whether they were under treatment. Our data indicate the need for interventions to reduce sodium intake, as well the need for ongoing, appropriate monitoring of salt consumption in the general population. PMID- 26132097 TI - Comment on "Association between Lifetime Exposure to Inorganic Arsenic in Drinking Water and Coronary Heart Disease in Colorado Residents". PMID- 26132096 TI - Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment. AB - The Morris water maze (MWM) is a commonly used task to assess hippocampal dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer's disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer's disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized. PMID- 26132098 TI - Analytical phenolic composition and sensory assessment of selected rare Greek cultivars after extended bottle ageing. PMID- 26132099 TI - Characterization of Phytophthora nicotianae isolates in southeast Spain and their detection and quantification through a real-time TaqMan PCR. PMID- 26132100 TI - Delays in Motor Development in Children with Down Syndrome. AB - BACKGROUND: Children with Down syndrome (DS) present with delays in motor development. The reduced size of the cerebrum, brain maturation disorders, and pathophysiological processes lead to motor development delay. The aim of this study was to examine the gross motor function and estimate what motor abilities are significantly delayed in children with Down syndrome even if they attend physical therapy sessions. Another purpose of the study was to assess the functional balance. MATERIAL AND METHODS: The study group consisted of 79 children with DS (42 boys, 37 girls), average age 6 years and 3 months +/- 4 years and 6 months. Participants were divided into 3 groups according to (i) age: <3 years old, 3-6 years old, and >6 years old; and (ii) motor impairment scale: mild (SNR 1), moderate (SNR 2), and severe (SNR 3). Children were assessed using the Gross Motor Function Measure-88 (GMFM-88) and Pediatric Balance Scale (PBS). RESULTS: None of the assessed children developed all the functions included in GMFM-88. The standing position was achieved at the specified age by 10% of children in the first age group (<3 years old) and 95% of children aged 3-6 years. Similarly, the walking ability was performed by 10% of children under 3 years old and by 95% of children aged 3-6 years. The median score of PBS was 50 points (min. 34 p. - max. 56 p.). There was a statistically significant correlation between PBS scores and GMFM-88 scores, r=0.7; p<0.0001, and between balance scores and GMFM - 88 E (walking, running, jumping) (r=0.64; p<0.0001). CONCLUSIONS: Motor development, especially standing position and walking ability, is delayed in children with Down syndrome. Balance and motor functions are correlated with each other, so both aspects of development should be consider together in physical therapy of children with Down syndrome. PMID- 26132101 TI - Corrigendum. PMID- 26132102 TI - Comparative Analysis of the Flexural Stiffness of Pinniped Vibrissae. AB - Vibrissae are important components of the mammalian tactile sensory system and are used to detect vibrotactile stimuli in the environment. Pinnipeds have the largest and most highly innervated vibrissae among mammals, and the hair shafts function as a biomechanical filter spanning the environmental stimuli and the neural mechanoreceptors deep in the follicle-sinus complex. Therefore, the material properties of these structures are critical in transferring vibrotactile information to the peripheral nervous system. Vibrissae were tested as cantilever beams and their flexural stiffness (EI) was measured to test the hypotheses that the shape of beaded vibrissae reduces EI and that vibrissae are anisotropic. EI was measured at two locations on each vibrissa, 25% and 50% of the overall length, and at two orientations to the point force. EI differed in orientations that were normal to each other, indicating a functional anisotropy. Since vibrissae taper from base to tip, the second moment of area (I) was lower at 50% than 25% of total length. The anterior orientation exhibited greater EI values at both locations compared to the dorsal orientation for all species. Smooth vibrissae were generally stiffer than beaded vibrissae. The profiles of beaded vibrissae are known to decrease the amplitude of vibrations when protruded into a flow field. The lower EI values of beaded vibrissae, along with the reduced vibrations, may function to enhance the sensitivity of mechanoreceptors to detection of small changes in flow from swimming prey by increasing the signal to noise ratio. This study builds upon previous morphological and hydrodynamic analyses of vibrissae and is the first comparative study of the mechanical properties of pinniped vibrissae. PMID- 26132103 TI - High Accuracy Decoding of Dynamical Motion from a Large Retinal Population. AB - Motion tracking is a challenge the visual system has to solve by reading out the retinal population. It is still unclear how the information from different neurons can be combined together to estimate the position of an object. Here we recorded a large population of ganglion cells in a dense patch of salamander and guinea pig retinas while displaying a bar moving diffusively. We show that the bar's position can be reconstructed from retinal activity with a precision in the hyperacuity regime using a linear decoder acting on 100+ cells. We then took advantage of this unprecedented precision to explore the spatial structure of the retina's population code. The classical view would have suggested that the firing rates of the cells form a moving hill of activity tracking the bar's position. Instead, we found that most ganglion cells in the salamander fired sparsely and idiosyncratically, so that their neural image did not track the bar. Furthermore, ganglion cell activity spanned an area much larger than predicted by their receptive fields, with cells coding for motion far in their surround. As a result, population redundancy was high, and we could find multiple, disjoint subsets of neurons that encoded the trajectory with high precision. This organization allows for diverse collections of ganglion cells to represent high accuracy motion information in a form easily read out by downstream neural circuits. PMID- 26132104 TI - Hyper Accumulation of Arsenic in Mutants of Ochrobactrum tritici Silenced for Arsenite Efflux Pumps. AB - Ochrobactrum tritici SCII24T is a highly As-resistant bacterium, with two previously described arsenic resistance operons, ars1 and ars2. Among a large number of genes, these operons contain the arsB and Acr3 genes that encode the arsenite efflux pumps responsible for arsenic resistance. Exploring the genome of O. tritici SCII24T, an additional putative operon (ars3) was identified and revealed the presence of the Acr3_2 gene that encodes for an arsenite efflux protein but which came to prove to not be required for full As resistance. The genes encoding for arsenite efflux pumps, identified in this strain, were inactivated to develop microbial accumulators of arsenic as new tools for bioremediation. Six different mutants were produced, studied and three were more useful as biotools. O. tritici wild type and the Acr3-mutants showed the highest resistance to As(III), being able to grow up to 50 mM of arsenite. On the other hand, arsB-mutants were not able to grow at concentrations higher than 1 mM As(III), and were the most As(III) sensitive mutants. In the presence of 1 mM As(III), the strain with arsB and Acr3_1 mutated showed the highest intracellular arsenic concentration (up to 17 ng(As)/mg protein), while in assays with 5 mM As(III), the single arsB-mutant was able to accumulate the highest concentration of arsenic (up to 10 ng(As)/mg protein). Therefore, arsB is the main gene responsible for arsenite resistance in O. tritici. However, both genes arsB and Acr3_1 play a crucial role in the resistance mechanism, depending on the arsenite concentration in the medium. In conclusion, at moderate arsenite concentrations, the double arsB- and Acr3_1-mutant exhibited a great ability to accumulate arsenite and can be seen as a promising bioremediation tool for environmental arsenic detoxification. PMID- 26132105 TI - Angiopoietin Like Protein 2 (ANGPTL2) Promotes Adipose Tissue Macrophage and T lymphocyte Accumulation and Leads to Insulin Resistance. AB - OBJECTIVES: Angiopoietin-like protein 2 (ANGPTL2), a recently identified pro inflammatory cytokine, is mainly secreted from the adipose tissue. This study aimed to explore the role of ANGPTL2 in adipose tissue inflammation and macrophage activation in a mouse model of diabetes. METHODOLOGY/PRINCIPAL FINDINGS: Adenovirus mediated lacZ (Ad-LacZ) or human ANGPTL2 (Ad-ANGPTL2) was delivered via tail vein in diabetic db/db mice. Ad-ANGPTL2 treatment for 2 weeks impaired both glucose tolerance and insulin sensitivity as compared to Ad-LacZ treatment. Ad-ANGPTL2 treatment significantly induced pro-inflammatory gene expression in white adipose tissue. We also isolated stromal vascular fraction from epididymal fat pad and analyzed adipose tissue macrophage and T lymphocyte populations by flow cytometry. Ad-ANGPTL2 treated mice had more adipose tissue macrophages (F4/80+CD11b+) and a larger M1 macrophage subpopulation (F4/80+CD11b+CD11c+). Moreover, Ad-ANGPTL2 treatment increased a CD8-positive T cell population in adipose tissue, which preceded increased macrophage accumulation. Consistent with our in vivo results, recombinant human ANGPTL2 protein treatment increased mRNA levels of pro-inflammatory gene products and production of TNF-alpha protein in the human macrophage-like cell line THP-1. Furthermore, Ad-ANGPTL2 treatment induced lipid accumulation and increased fatty acid synthesis, lipid metabolism related gene expression in mouse liver. CONCLUSION: ANGPTL2 treatment promotes macrophage accumulation and activation. These results suggest potential mechanisms for insulin resistance. PMID- 26132106 TI - A Neural Model of Distance-Dependent Percept of Object Size Constancy. AB - Size constancy is one of the well-known visual phenomena that demonstrates perceptual stability to account for the effect of viewing distance on retinal image size. Although theories involving distance scaling to achieve size constancy have flourished based on psychophysical studies, its underlying neural mechanisms remain unknown. Single cell recordings show that distance-dependent size tuned cells are common along the ventral stream, originating from V1, V2, and V4 leading to IT. In addition, recent research employing fMRI demonstrates that an object's perceived size, associated with its perceived egocentric distance, modulates its retinotopic representation in V1. These results suggest that V1 contributes to size constancy, and its activity is possibly regulated by feedback of distance information from other brain areas. Here, we propose a neural model based on these findings. First, we construct an egocentric distance map in LIP by integrating horizontal disparity and vergence through gain modulated MT neurons. Second, LIP neurons send modulatory feedback of distance information to size tuned cells in V1, resulting in a spread of V1 cortical activity. This process provides V1 with distance-dependent size representations. The model supports that size constancy is preserved by scaling retinal image size to compensate for changes in perceived distance, and suggests a possible neural circuit capable of implementing this process. PMID- 26132108 TI - A conversation with Robert Schrier [interview by Ushma S. Neill]. PMID- 26132107 TI - Metasynthesis: Experiences of Women with Severe Maternal Morbidity and Their Perception of the Quality of Health Care. AB - AIM: To explore the experiences of women with severe maternal morbidity and their perception of the quality of health care. BACKGROUND: The exploration of factors associated with severe maternal morbidity has emerged as an alternative strategy in reducing maternal mortality. This approach is useful for the evaluation and improvement of maternal health services. DESIGN: Included a comprehensive search, appraisal of reports of qualitative studies, the classification of studies and the synthesis of findings. DATA SOURCES: A literature search was conducted through nine databases for articles published between January 1980 and August 2013. REVIEW METHODS: The quality of included studies was assessed with a modified Critical Appraisal Skills Program tool. The synthesis applied a meta ethnographic approach. It involved (1) identifying and comparing the findings; (2) creating a parsimonious thematic structure and (3) searching for disconfirming data. RESULTS: Nine studies published between 2005 and 2012, involving 292 women with severe maternal morbidity, were included. Three key themes were identified: 'provision of care', 'severe maternal morbidity' and 'health care seeking behavior'. Barriers to the access and utilization of heath care services were identified. CONCLUSION: The findings appear to suggest that mental and physical health outcomes of women who experienced severe maternal morbidity were poor. There is a need to identify the persistence and severity of these outcomes over a longer period of time. More realistic and less biased information may be obtained in community-based interviews. The impact of potential negative fetal outcomes would be a strong influencing factor for the women. These findings may help to increase awareness of the non-physical components of severe maternal morbidity and provide guidance for professionals regarding preventive measures. PMID- 26132110 TI - Quality Heterostructures from Two-Dimensional Crystals Unstable in Air by Their Assembly in Inert Atmosphere. AB - Many layered materials can be cleaved down to individual atomic planes, similar to graphene, but only a small minority of them are stable under ambient conditions. The rest react and decompose in air, which has severely hindered their investigation and potential applications. Here we introduce a remedial approach based on cleavage, transfer, alignment, and encapsulation of air sensitive crystals, all inside a controlled inert atmosphere. To illustrate the technology, we choose two archetypal two-dimensional crystals that are of intense scientific interest but are unstable in air: black phosphorus and niobium diselenide. Our field-effect devices made from their monolayers are conductive and fully stable under ambient conditions, which is in contrast to the counterparts processed in air. NbSe2 remains superconducting down to the monolayer thickness. Starting with a trilayer, phosphorene devices reach sufficiently high mobilities to exhibit Landau quantization. The approach offers a venue to significantly expand the range of experimentally accessible two dimensional crystals and their heterostructures. PMID- 26132111 TI - Insights into the Molecular Dynamics in Polysulfone Polymers from (13)C Solid State NMR Experiments. AB - The molecular and segmental motions in three different grades of ductile polysulfone polymers; poly(ether sulfone) (PESU), polysulfone (PSU), and poly(phenyl sulfone) (PPSU) are probed using (13)C solid-state NMR experiments. Polarization inversion spin exchange at magic angle (PISEMA) experiments indicates that the phenyl rings in the polymers are undergoing pi-flip motions on the order of 100 kHz. The temperature dependent PISEMA experiments show that the fraction of mobile regions that undergoes aromatic pi-flips is higher in PPSU than in the other two polymers. The center band only detection of exchange (CODEX) experiments was carried out and was unable to detect any slow segmental motions in the chains. A combination of (13)C spin-lattice relaxation time (T1) and T1-filtered PISEMA experiments show that the mobile regions in all the polymers are dynamically heterogeneous. PMID- 26132109 TI - Hurdles to clinical translation of human induced pluripotent stem cells. AB - Human pluripotent stem cells are known to have the capacity to renew indefinitely, being intrinsically able to differentiate into many different cell types. These characteristics have generated tremendous enthusiasm about the potential applications of these cells in regenerative medicine. However, major challenges remain with the development and testing of novel experimental stem cell therapeutics in the field. In this Review, we focus on the nature of the preclinical challenges and discuss potential solutions that could help overcome them. Furthermore, we discuss the use of allogeneic versus autologous stem cell products, including a review of their respective advantages and disadvantages, major clinical requirements, quality standards, time lines, and costs of clinical grade development. PMID- 26132112 TI - The effect of mucosal cuff shrinkage around dental implants during healing abutment replacement. AB - Soft tissue shrinkage during the course of restoring dental implants may result in biological and prosthodontic difficulties. This study was conducted to measure the continuous shrinkage of the mucosal cuff around dental implants following the removal of the healing abutment up to 60 s. Individuals treated with implant supported fixed partial dentures were included. Implant data--location, type, length, diameter and healing abutments' dimensions--were recorded. Mucosal cuff shrinkage, following removal of the healing abutments, was measured in bucco lingual direction at four time points--immediately after 20, 40 and 60 s. anova was used to for statistical analysis. Eighty-seven patients (49 women and 38 men) with a total of 311 implants were evaluated (120 maxilla; 191 mandible; 291 posterior segments; 20 anterior segments). Two-hundred and five (66%) implants displayed thick and 106 (34%) thin gingival biotype. Time was the sole statistically significant parameter affecting mucosal cuff shrinkage around dental implants (P < 0.001). From time 0 to 20, 40 and 60 s, the mean diameter changed from 4.1 to 4.07, 3.4 and 2.81 mm, respectively. The shrinkage was 1%, 17% and 31%, respectively. The gingival biotype had no statistically significant influence on mucosal cuff shrinkage (P = 0.672). Time required replacing a healing abutment with a prosthetic element should be minimised (up to 20/40 s), to avoid pain, discomfort and misfit. PMID- 26132113 TI - Organic Dye-Sensitized Tandem Photoelectrochemical Cell for Light Driven Total Water Splitting. AB - Light driven water splitting was achieved by a tandem dye-sensitized photoelectrochemical cell with two photoactive electrodes. The photoanode is constituted by an organic dye L0 as photosensitizer and a molecular complex Ru1 as water oxidation catalyst on meso-porous TiO2, while the photocathode is constructed with an organic dye P1 as photoabsorber and a molecular complex Co1 as hydrogen generation catalyst on nanostructured NiO. By combining the photocathode and the photoanode, this tandem DS-PEC cell can split water by visible light under neutral pH conditions without applying any bias. PMID- 26132114 TI - Factors Affecting the Uptake of HIV Testing among Men: A Mixed-Methods Study in Rural Burkina Faso. AB - BACKGROUND: This study aimed to explore factors shaping the decision to undergo Human Immunodeficiency Virus (HIV) testing among men in rural Burkina Faso. METHODS: The study took place in 2009 in the Nouna Health District and adopted a triangulation mixed methods design. The quantitative component relied on data collected through a structured survey on a representative sample of 1130 households. The qualitative component relied on 38 in-depth interviews, with men purposely selected to represent variation in testing decision, age, and place of residence. A two-part model was conducted, with two distinct outcome variables, i.e. "being offered an HIV test" and "having done an HIV test". The qualitative data analysis relied on inductive coding conducted by three independent analysts. RESULT: Of the 937 men, 357 had been offered an HIV test and 97 had taken the test. Younger age, household wealth, living in a village under demographic surveillance, and knowing that HIV testing is available at primary health facilities were all positively associated with the probability of being offered an HIV test. Household wealth and literacy were found to be positively associated, and distance was found to be negatively associated with the probability of having taken an HIV test. Qualitative findings indicated that the limited uptake of HIV testing was linked to poor knowledge on service availability and to low risk perceptions. CONCLUSION: With only 10% of the total sample ever having tested for HIV, our study confirmed that male HIV testing remains unacceptably low in Sub-Saharan Africa. This results from a combination of health system factors, indicating general barriers to access, and motivational factors, such as one's own knowledge of service availability and risk perceptions. Our findings suggested that using antenatal care and curative services as the exclusive entry points into HIV testing may not be sufficient to reach large portions of the male population. Thus, additional strategies are urgently needed to increase service uptake. PMID- 26132115 TI - Tracking Human Mobility Using WiFi Signals. AB - We study six months of human mobility data, including WiFi and GPS traces recorded with high temporal resolution, and find that time series of WiFi scans contain a strong latent location signal. In fact, due to inherent stability and low entropy of human mobility, it is possible to assign location to WiFi access points based on a very small number of GPS samples and then use these access points as location beacons. Using just one GPS observation per day per person allows us to estimate the location of, and subsequently use, WiFi access points to account for 80% of mobility across a population. These results reveal a great opportunity for using ubiquitous WiFi routers for high-resolution outdoor positioning, but also significant privacy implications of such side-channel location tracking. PMID- 26132118 TI - Correction. PMID- 26132117 TI - Establishment of a Clinically Relevant Ex Vivo Mock Cataract Surgery Model for Investigating Epithelial Wound Repair in a Native Microenvironment. AB - The major impediment to understanding how an epithelial tissue executes wound repair is the limited availability of models in which it is possible to follow and manipulate the wound response ex vivo in an environment that closely mimics that of epithelial tissue injury in vivo. This issue was addressed by creating a clinically relevant epithelial ex vivo injury-repair model based on cataract surgery. In this culture model, the response of the lens epithelium to wounding can be followed live in the cells' native microenvironment, and the molecular mediators of wound repair easily manipulated during the repair process. To prepare the cultures, lenses are removed from the eye and a small incision is made in the anterior of the lens from which the inner mass of lens fiber cells is removed. This procedure creates a circular wound on the posterior lens capsule, the thick basement membrane that surrounds the lens. This wound area where the fiber cells were attached is located just adjacent to a continuous monolayer of lens epithelial cells that remains linked to the lens capsule during the surgical procedure. The wounded epithelium, the cell type from which fiber cells are derived during development, responds to the injury of fiber cell removal by moving collectively across the wound area, led by a population of vimentin-rich repair cells whose mesenchymal progenitors are endogenous to the lens. These properties are typical of a normal epithelial wound healing response. In this model, as in vivo, wound repair is dependent on signals supplied by the endogenous environment that is uniquely maintained in this ex vivo culture system, providing an ideal opportunity for discovery of the mechanisms that regulate repair of an epithelium following wounding. PMID- 26132116 TI - Unravelling the Structural and Molecular Basis Responsible for the Anti-Biofilm Activity of Zosteric Acid. AB - The natural compound zosteric acid, or p-(sulfoxy)cinnamic acid (ZA), is proposed as an alternative biocide-free agent suitable for preventive or integrative anti biofilm approaches. Despite its potential, the lack of information concerning the structural and molecular mechanism of action involved in its anti-biofilm activity has limited efforts to generate more potent anti-biofilm strategies. In this study a 43-member library of small molecules based on ZA scaffold diversity was designed and screened against Escherichia coli to understand the structural requirements necessary for biofilm inhibition at sub-lethal concentrations. Considerations concerning the relationship between structure and anti-biofilm activity revealed that i) the para-sulfoxy ester group is not needed to exploit the anti-biofilm activity of the molecule, it is the cinnamic acid scaffold that is responsible for anti-biofilm performance; ii) the anti-biofilm activity of ZA derivatives depends on the presence of a carboxylate anion and, consequently, on its hydrogen-donating ability; iii) the conjugated aromatic system is instrumental to the anti-biofilm activities of ZA and its analogues. Using a protein pull-down approach, combined with mass spectrometry, the herein-defined active structure of ZA was matrix-immobilized, and was proved to interact with the E. coli NADH:quinone reductase, WrbA, suggesting a possible role of this protein in the biofilm formation process. PMID- 26132119 TI - Emphasizing Oral Health Care in Children with Down Syndrome. PMID- 26132122 TI - Type 2 Diabetes: Updated Evidence Requires Updated Decision Making. PMID- 26132123 TI - The Role of Levetiracetam in Treating Chronic Neuropathic Pain Symptoms. PMID- 26132124 TI - Management of Blood Glucose with Noninsulin Therapies in Type 2 Diabetes. AB - A comprehensive, collaborative approach is necessary for optimal treatment of patients with type 2 diabetes mellitus. Treatment guidelines focus on nutrition, exercise, and pharmacologic therapies to prevent and manage complications. Patients with prediabetes or new-onset diabetes should receive individualized medical nutrition therapy, preferably from a registered dietitian, as needed to achieve treatment goals. Patients should be treated initially with metformin because it is the only medication shown in randomized controlled trials to reduce mortality and complications. Additional medications such as sulfonylureas, dipeptidyl-peptidase-4 inhibitors, thiazolidinediones, and glucagon-like peptide 1 receptor agonists should be added as needed in a patient-centered fashion. However, there is no evidence that any of these medications reduce the risk of diabetes-related complications, cardiovascular mortality, or all-cause mortality. There is insufficient evidence on which combination of hypoglycemic agents best improves health outcomes before escalating to insulin therapy. The American Diabetes Association recommends an A1C goal of less than 7% for many nonpregnant adults, with the option of a less stringent goal of less than 8% for patients with short life expectancy, cardiovascular risk factors, or long-standing diabetes. Randomized trials in middle-aged patients with cardiovascular risk factors have shown no mortality benefit and in some cases increased mortality with more stringent A1C targets. PMID- 26132125 TI - Differential Diagnosis of Polyarticular Arthritis. AB - Polyarticular arthritis is commonly encountered in clinical settings and has multiple etiologies. The first step is to distinguish between true articular pain and nonarticular or periarticular conditions by recognizing clinical patterns through the history and physical examination. Once pain within a joint or joints is confirmed, the next step is to classify the pain as noninflammatory or inflammatory in origin. Noninflammatory arthritis, which is mostly related to osteoarthritis, has a variable onset and severity and does not have inflammatory features, such as warm or swollen joints. Osteoarthritis usually presents with less than one hour of morning stiffness and pain that is aggravated by activity and improves with rest. A review of systems is usually negative for rashes, oral ulcers, or other internal organ involvement. In contrast, inflammatory arthritis generally causes warm, swollen joints; prolonged morning stiffness; and positive findings on a review of systems. Once inflammatory arthritis is suspected, possible diagnoses are sorted by the pattern of joint involvement, which includes number and type of joints involved, symmetry, and onset. The suspicion for inflammatory arthritis should be confirmed by the appropriate serologic/tissue and/or imaging studies in the clinical setting or in consultation with a subspecialist. PMID- 26132126 TI - Evaluation of Short and Tall Stature in Children. AB - Short stature is defined as a height more than two standard deviations below the mean for age (less than the 3rd percentile). Tall stature is defined as a height more than two standard deviations above the mean for age (greater than the 97th percentile). The initial evaluation of short and tall stature should include a history and physical examination, accurate serial measurements, and determination of growth velocity, midparental height, and bone age. Common normal variants of short stature are familial short stature, constitutional delay of growth and puberty, and idiopathic short stature. Pathologic causes of short stature include chronic diseases; growth hormone deficiency; and genetic disorders, such as Turner syndrome. Tall stature has the same prevalence as short stature, but it is a much less common reason for referral to subspecialty care. Common causes of tall stature include familial tall stature, obesity, Klinefelter syndrome, Marfan syndrome, and precocious puberty. Although most children with short or tall stature have variants of normal growth, children who are more than three standard deviations from the mean for age are more likely to have underlying pathology. Evaluation for pathologic etiologies is guided by history and physical examination findings. PMID- 26132131 TI - Pruritic Plaques After Laparoscopic Surgery. PMID- 26132132 TI - Growth Hormone for Treatment of Idiopathic Short Stature in Children. PMID- 26132134 TI - Nicotine Replacement Therapy for Smoking Cessation. PMID- 26132135 TI - Mycobacterium tuberculosis and Human Immunodeficiency Virus Type 1 Cooperatively Modulate Macrophage Apoptosis via Toll Like Receptor 2 and Calcium Homeostasis. AB - The emergence of drug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) together with reports of co-infections with the human immunodeficiency virus (HIV) has renewed interest to better understand the intricate mechanisms prevalent during co-infections. In this study we report a synergistic effect of M. tuberculosis and HIV-1, and their antigens Rv3416 and Nef, respectively, in inhibiting apoptosis of macrophages. This inhibition involves the TLR2 pathway and second messengers that play complementing and contrasting roles in regulating apoptosis. Interestingly, the route of calcium influx into cells differentially regulates apoptosis during antigenic co stimulation. While calcium released from intracellular stores was anti-apoptotic, calcium influx from the external milieu was pro-apoptotic. Further, molecular sensors of intracellular calcium release aid in antigen mediated inhibition of apoptosis. A cross-regulation between oxidative burst and differential routing of calcium influx governed apoptosis. Interestingly, the HIV-1 Nef supported anti apoptotic responses in macrophages whereas Vpu had no significant effect. These results point to a synergistic liaison between M. tuberculosis and HIV-1 in regulating macrophage apoptosis. PMID- 26132136 TI - Use of Time-Resolved Fluorescence to Monitor Bioactive Compounds in Plant Based Foodstuffs. AB - The study of compounds that exhibit antioxidant activity has recently received much interest in the food industry because of their potential health benefits. Most of these compounds are plant based, such as polyphenolics and carotenoids, and there is a need to monitor them from the field through processing and into the body. Ideally, a monitoring technique should be non-invasive with the potential for remote capabilities. The application of the phenomenon of fluorescence has proved to be well suited, as many plant associated compounds exhibit fluorescence. The photophysical behaviour of fluorescent molecules is also highly dependent on their microenvironment, making them suitable probes to monitor changes in pH, viscosity and polarity, for example. Time-resolved fluorescence techniques have recently come to the fore, as they offer the ability to obtain more information, coupled with the fact that the fluorescence lifetime is an absolute measure, while steady state just provides relative and average information. In this work, we will present illustrative time-resolved measurements, rather than a comprehensive review, to show the potential of time resolved fluorescence applied to the study of bioactive substances. The aim is to help assess if any changes occur in their form, going from extraction via storage and cooking to the interaction with serum albumin, a principal blood transport protein. PMID- 26132138 TI - Nanoindentation, High-Temperature Behavior, and Crystallographic/Spectroscopic Characterization of the High-Refractive-Index Materials TiTa2O7 and TiNb2O7. AB - Colorless single crystals, as well as polycrystalline samples of TiTa2O7 and TiNb2O7, were grown directly from the melt and prepared by solid-state reactions, respectively, at various temperatures between 1598 K and 1983 K. The chemical composition of the crystals was confirmed by wavelength-dispersive X-ray spectroscopy, and the crystal structures were determined using single-crystal X ray diffraction. Structural investigations of the isostructural compounds resulted in the following basic crystallographic data: monoclinic symmetry, space group I2/m (No. 12), a = 17.6624(12) A, b = 3.8012(3) A, c = 11.8290(9) A, beta = 95.135(7) degrees , V = 790.99(10) A(3) for TiTa2O7 and a = 17.6719(13) A, b = 3.8006(2) A, c = 11.8924(9) A, beta = 95.295(7) degrees , V = 795.33(10) A(3), respectively, for TiNb2O7, Z = 6. Rietveld refinement analyses of the powder X ray diffraction patterns and Raman spectroscopy were carried out to complement the structural investigations. In addition, in situ high-temperature powder X-ray diffraction experiments over the temperature range of 323-1323 K enabled the study of the thermal expansion tensors of TiTa2O7 and TiNb2O7. To determine the hardness (H), and elastic moduli (E) of the chemical compounds, nanoindentation experiments have been performed with a Berkovich diamond indenter tip. Analyses of the load-displacement curves resulted in a hardness of H = 9.0 +/- 0.5 GPa and a reduced elastic modulus of Er = 170 +/- 7 GPa for TiTa2O7. TiNb2O7 showed a slightly lower hardness of H = 8.7 +/- 0.3 GPa and a reduced elastic modulus of Er = 159 +/- 4 GPa. Spectroscopic ellipsometry of the polished specimens was employed for the determination of the optical constants n and k. TiNb2O7 as well as TiTa2O7 exhibit a very high average refractive index of nD = 2.37 and nD = 2.29, respectively, at lambda = 589 nm, similar to that of diamond (nD = 2.42). PMID- 26132137 TI - Interrelationship of Multiple Endothelial Dysfunction Biomarkers with Chronic Kidney Disease. AB - The interrelationship of multiple endothelial biomarkers and chronic kidney disease (CKD) has not been well studied. We measured asymmetric dimethylarginine (ADMA), L-arginine, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), von Willebrand factor (vWF), flow-mediated dilation (FMD), and nitroglycerin-induced dilation (NID) in 201 patients with CKD and 201 community-based controls without CKD. Multivariable analyses were used to examine the interrelationship of endothelial biomarkers with CKD. The multivariable-adjusted medians (interquartile ranges) were 0.54 (0.40, 0.75) in patients with CKD vs. 0.25 (0.22, 0.27) MUmol /L in controls without CKD (p<0.0001 for group difference) for ADMA; 67.0 (49.6, 86.7) vs. 31.0 (27.7, 34.2) MUmol/L (p<0.0001) for L-arginine; 230.0 (171.6, 278.6) vs. 223.9 (178.0, 270.6) ng/mL (p=0.55) for sICAM-1; 981.7 (782.6, 1216.8) vs. 633.2 (507.8, 764.3) ng/mL (p<0.0001) for sVCAM-1; 47.9 (35.0, 62.5) vs. 37.0 (28.9, 48.0) ng/mL (p=0.01) for sE-selectin; 1320 (1044, 1664) vs. 1083 (756, 1359) mU/mL (p=0.008) for vWF; 5.74 (3.29, 8.72) vs. 8.80 (6.50, 11.39)% (p=0.01) for FMD; and 15.2 (13.5, 16.9) vs. 19.1 (17.2, 21.0)% (p=0.0002) for NID, respectively. In addition, the severity of CKD was positively associated with ADMA, L-arginine, sVCAM-1, sE-selectin, and vWF and inversely associated with FMD and NID. Furthermore, FMD and NID were significantly and inversely correlated with ADMA, L-arginine, sVCAM-1, sE-selectin, and vWF. In conclusion, these data indicate that multiple dysfunctions of the endothelium were present among patients with CKD. Interventional studies are warranted to test the effects of treatment of endothelial dysfunction on CKD. PMID- 26132139 TI - Widespread Forest Vertebrate Extinctions Induced by a Mega Hydroelectric Dam in Lowland Amazonia. AB - Mega hydropower projects in tropical forests pose a major emergent threat to terrestrial and freshwater biodiversity worldwide. Despite the unprecedented number of existing, under-construction and planned hydroelectric dams in lowland tropical forests, long-term effects on biodiversity have yet to be evaluated. We examine how medium and large-bodied assemblages of terrestrial and arboreal vertebrates (including 35 mammal, bird and tortoise species) responded to the drastic 26-year post-isolation history of archipelagic alteration in landscape structure and habitat quality in a major hydroelectric reservoir of Central Amazonia. The Balbina Hydroelectric Dam inundated 3,129 km2 of primary forests, simultaneously isolating 3,546 land-bridge islands. We conducted intensive biodiversity surveys at 37 of those islands and three adjacent continuous forests using a combination of four survey techniques, and detected strong forest habitat area effects in explaining patterns of vertebrate extinction. Beyond clear area effects, edge-mediated surface fire disturbance was the most important additional driver of species loss, particularly in islands smaller than 10 ha. Based on species-area models, we predict that only 0.7% of all islands now harbor a species-rich vertebrate assemblage consisting of >=80% of all species. We highlight the colossal erosion in vertebrate diversity driven by a man-made dam and show that the biodiversity impacts of mega dams in lowland tropical forest regions have been severely overlooked. The geopolitical strategy to deploy many more large hydropower infrastructure projects in regions like lowland Amazonia should be urgently reassessed, and we strongly advise that long-term biodiversity impacts should be explicitly included in pre-approval environmental impact assessments. PMID- 26132140 TI - A randomised controlled trial of oral zinc sulphate for primary dysmenorrhoea in adolescent females. AB - BACKGROUND: Primary dysmenorrhoea, the most common gynaecologic problem of adolescent females, is commonly treated with nonsteroidal anti-inflammatory drugs or oral contraceptive pills. AIM: To compare the effect of zinc sulphate with that of placebo on the control of pain severity and duration in adolescent girls with primary dysmenorrhoea. MATERIALS AND METHODS: In a three-month randomised double-blind placebo-controlled clinical trial, 120 adolescent females with primary dysmenorrhoea were randomly divided into two groups of sixty: an intervention group (zinc) and a control group (placebo). Zinc was administered in the form of a capsule containing 50 mg/day zinc sulphate beginning on the first day of menses and continuing until three days prior to the end of menses. Each month, the duration and severity of primary dysmenorrhoea were determined. Severity scoring was performed by using a 0-10 scaling system. RESULTS: In the first month, the duration of pain was significantly lower in the zinc group compared with the placebo group (P-value = 0.044), while there was no significant difference in pain severity between the groups (P-value = 0.497). In the second and third month, pain severity and duration in the zinc group were significantly lower than the placebo group (P-value <0.001). CONCLUSION: Both pain duration and pain severity were decreased by taking oral zinc. The results of our interventional study suggests that zinc may be used to treat primary dysmenorrhoea in adolescents. PMID- 26132141 TI - Electrochemical liquid-liquid-solid (ec-LLS) crystal growth: a low-temperature strategy for covalent semiconductor crystal growth. AB - This Account describes a new electrochemical synthetic strategy for direct growth of crystalline covalent group IV and III-V semiconductor materials at or near ambient temperature conditions. This strategy, which we call "electrochemical liquid-liquid-solid" (ec-LLS) crystal growth, marries the semiconductor solvation properties of liquid metal melts with the utility and simplicity of conventional electrodeposition. A low-temperature liquid metal (i.e., Hg, Ga, or alloy thereof) acts simultaneously as the source of electrons for the heterogeneous reduction of oxidized semiconductor precursors dissolved in an electrolyte as well as the solvent for dissolution of the zero-valent semiconductor. Supersaturation of the semiconductor in the liquid metal triggers eventual crystal nucleation and growth. In this way, the liquid electrolyte-liquid metal solid crystal phase boundary strongly influences crystal growth. As a synthetic strategy, ec-LLS has several intrinsic features that are attractive for preparing covalent semiconductor crystals. First, ec-LLS does not require high temperatures, toxic precursors, or high-energy-density semiconductor reagents. This largely simplifies equipment complexity and expense. In practice, ec-LLS can be performed with only a beaker filled with electrolyte and an electrical circuit capable of supplying a defined current (e.g., a battery in series with a resistor). By this same token, ec-LLS is compatible with thermally and chemically sensitive substrates (e.g., plastics) that cannot be used as deposition substrates in conventional syntheses of covalent semiconductors. Second, ec-LLS affords control over a host of crystal shapes and sizes through simple changes in common experimental parameters. As described in detail herein, large and small semiconductor crystals can be grown both homogeneously within a liquid metal electrode and heterogeneously at the interface of a liquid metal electrode and a seed substrate, depending on the particular details chosen for ec-LLS. Third, the rate of introduction of zero-valent materials into the liquid metal is precisely gated with a high degree of resolution by the applied potential/current. The intent of this Account is to summarize the key elements of ec-LLS identified to date, first contextualizing this method with respect to other semiconductor crystal growth methods and then highlighting some unique capabilities of ec-LLS. Specifically, we detail ec-LLS as a platform to prepare Ge and Si crystals from bulk- (~1 cm(3)), micro- (~10(-10) cm(3)), and nano-sized (~10(-16) cm(3)) liquid metal electrodes in common solvents at low temperature. In addition, we describe our successes in the preparation of more compositionally complex binary covalent III-V semiconductors. PMID- 26132142 TI - Time of HIV Diagnosis and Engagement in Prenatal Care Impact Virologic Outcomes of Pregnant Women with HIV. AB - BACKGROUND: HIV suppression at parturition is beneficial for maternal, fetal and public health. To eliminate mother-to-child transmission of HIV, an understanding of missed opportunities for antiretroviral therapy (ART) use during pregnancy and HIV suppression at delivery is required. METHODOLOGY: We performed a retrospective analysis of 836 mother-to-child pairs involving 656 HIV-infected women in Philadelphia, 2005-2013. Multivariable regression examined associations between patient (age, race/ethnicity, insurance status, drug use) and clinical factors such as adequacy of prenatal care measured by the Kessner index which classifies prenatal care as inadequate, intermediate, or adequate prenatal care; timing of HIV diagnosis; and the outcomes: receipt of ART during pregnancy and viral suppression at delivery. RESULTS: Overall, 25% of the sample was diagnosed with HIV during pregnancy; 39%, 38%, and 23% were adequately, intermediately, and inadequately engaged in prenatal care. Eight-five percent of mother-to-child pairs received ART during pregnancy but only 52% achieved suppression at delivery. Adjusting for patient factors, pairs diagnosed with HIV during pregnancy were less likely to receive ART (AOR 0.39, 95% CI 0.25-0.61) and achieve viral suppression (AOR 0.70, 95% CI 0.49-1.00) than those diagnosed before pregnancy. Similarly, women with inadequate prenatal care were less likely to receive ART (AOR 0.06, 95% CI 0.03-0.11) and achieve viral suppression (AOR 0.31, 95% CI 0.20-0.47) than those with adequate prenatal care. CONCLUSIONS: Targeted interventions to diagnose HIV prior to pregnancy and engage HIV-infected women in prenatal care have the potential to improve HIV related outcomes in the perinatal period. PMID- 26132143 TI - Involvement of Tetraspanin C189 in Cell-to-Cell Spreading of the Dengue Virus in C6/36 Cells. AB - Dengue virus (DENV) is naturally transmitted by mosquitoes to humans, infecting cells of both hosts. Unlike in mammalian cells, DENV usually does not cause extremely deleterious effects on cells of mosquitoes. Despite this, clustered progeny virions were found to form infection foci in a high density cell culture. It is thus interesting to know how the virus spreads among cells in tissues such as the midgut within live mosquitoes. This report demonstrates that cell-to-cell spread is one way for DENV to infect neighboring cells without depending on the "release and entry" mode. In the meantime, a membrane-bound vacuole incorporating tetraspanin C189 was formed in response to DENV infection in the C6/36 cell and was subsequently transported along with the contained virus from one cell to another. Knockdown of C189 in DENV-infected C6/36 cells is shown herein to reduce cell-to-cell transmission of the virus, which may be recovered by co-transfection with a C189-expressing vector in DENV-infected C6/36 cells. Moreover, cell-to cell transmission usually occurred at the site where the donor cell directly contacts the recipient cell. It suggested that C189 is crucially involved in the intercellular spread of progeny viral particles between mosquito cells. This novel finding presumably accounts for the rapid and efficient infection of DENV after its initial replication within tissues of the mosquito. PMID- 26132144 TI - Rigidity Emerges during Antibody Evolution in Three Distinct Antibody Systems: Evidence from QSFR Analysis of Fab Fragments. AB - The effects of somatic mutations that transform polyspecific germline (GL) antibodies to affinity mature (AM) antibodies with monospecificity are compared among three GL-AM Fab pairs. In particular, changes in conformational flexibility are assessed using a Distance Constraint Model (DCM). We have previously established that the DCM can be robustly applied across a series of antibody fragments (VL to Fab), and subsequently, the DCM was combined with molecular dynamics (MD) simulations to similarly characterize five thermostabilizing scFv mutants. The DCM is an ensemble based statistical mechanical approach that accounts for enthalpy/entropy compensation due to network rigidity, which has been quite successful in elucidating conformational flexibility and Quantitative Stability/Flexibility Relationships (QSFR) in proteins. Applied to three disparate antibody systems changes in QSFR quantities indicate that the VH domain is typically rigidified, whereas the VL domain and CDR L2 loop become more flexible during affinity maturation. The increase in CDR H3 loop rigidity is consistent with other studies in the literature. The redistribution of conformational flexibility is largely controlled by nonspecific changes in the H bond network, although certain Arg to Asp salt bridges create highly localized rigidity increases. Taken together, these results reveal an intricate flexibility/rigidity response that accompanies affinity maturation. PMID- 26132145 TI - Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala: An 18-Month Follow-Up. AB - Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory. PMID- 26132146 TI - Evaluation of Synergistic Antibacterial and Antioxidant Efficacy of Essential Oils of Spices and Herbs in Combination. AB - The present study was carried out to evaluate the possible synergistic interactions on antibacterial and antioxidant efficacy of essential oils of some selected spices and herbs [bay leaf, black pepper, coriander (seed and leaf), cumin, garlic, ginger, mustard, onion and turmeric] in combination. Antibacterial combination effect was evaluated against six important food-borne bacteria (Bacillus cereus, Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Salmonella typhimurium) using microbroth dilution, checkerboard titration and time-kill methods. Antioxidant combination effect was assessed by DPPH free radical scavenging method. Total phenolic content was measured by Folin-Ciocalteu method. Bioactivity -guided fractionation of active essential oils for isolation of bioactive compounds was done using TLC bioautography assay and chemical characterization (qualitative and quantitative) of bioactive compounds was performed using DART-MS and HPLC analyses. Cytotoxic potential was evaluated by brine shrimp lethality assay as well as MTT assay using human normal colon cell line. Results showed that among the possible combinations tested only coriander/cumin seed oil combination showed synergistic interactions both in antibacterial (FICI : 0.25-0.50) and antioxidant (CI : 0.79) activities. A high positive correlation between total phenolic content and antibacterial activity against most of the studied bacteria (R2 = 0.688 - 0.917) as well as antioxidant capacity (R2 = 0.828) was also observed. TLC-bioautography guided screening and subsequent combination studies revealed that two compounds corresponding to Rf values 0.35 from coriander seed oil and 0.53 from cumin seed oil exhibited both synergistic antibacterial and antioxidant activities. The bioactive compound corresponding to Rf 0.35 from coriander seed oil was identified as linalool (68.69%) and the bioactive compound corresponding to Rf 0.53 from cumin seed oil was identified as p-coumaric acid (7.14%) by DART-MS and HPLC analyses. The coriander/cumin seed oil combination did not show any cytotoxic effect both in brine shrimp lethality as well as human normal colon cell line assays. The LC50 in brine shrimp lethality assay was found to be 4945.30 MUg/ml and IC50 in human normal colon cell line was > 1000 MUg/ml. The results provide evidence that coriander/cumin seed oil combination might indeed be used as a potential source of safe and effective natural antimicrobial and antioxidant agents in pharmaceutical and food industries. PMID- 26132154 TI - pvsR: An Open Source Interface to Big Data on the American Political Sphere. AB - Digital data from the political sphere is abundant, omnipresent, and more and more directly accessible through the Internet. Project Vote Smart (PVS) is a prominent example of this big public data and covers various aspects of U.S. politics in astonishing detail. Despite the vast potential of PVS' data for political science, economics, and sociology, it is hardly used in empirical research. The systematic compilation of semi-structured data can be complicated and time consuming as the data format is not designed for conventional scientific research. This paper presents a new tool that makes the data easily accessible to a broad scientific community. We provide the software called pvsR as an add-on to the R programming environment for statistical computing. This open source interface (OSI) serves as a direct link between a statistical analysis and the large PVS database. The free and open code is expected to substantially reduce the cost of research with PVS' new big public data in a vast variety of possible applications. We discuss its advantages vis-a-vis traditional methods of data generation as well as already existing interfaces. The validity of the library is documented based on an illustration involving female representation in local politics. In addition, pvsR facilitates the replication of research with PVS data at low costs, including the pre-processing of data. Similar OSIs are recommended for other big public databases. PMID- 26132155 TI - Population Screening for Chronic Q-Fever Seven Years after a Major Outbreak. AB - INTRODUCTION: From 2007 through 2010, the Netherlands experienced a large Q-fever epidemic, with 4,107 notifications. The most serious complication of Q-fever is chronic Q-fever. METHOD: In 2014, we contacted all 2,161 adult inhabitants of the first village in the Netherlands affected by the Q-fever epidemic and offered to test for antibodies against Coxiella burnetii using immunofluorescence assay (IFA) to screen for chronic infections and assess whether large-scale population screening elsewhere is warranted. RESULTS: Of the 1,517 participants, 33.8% were IFA-positive. Six IFA-positive participants had an IgG phase I titer >=1:512. Two of these six participants were previously diagnosed with chronic Q-fever. Chronic infection was diagnosed in one of the other four participants after clinical examination. CONCLUSIONS: Seven years after the initial outbreak, seroprevalence remains high, but the yield of screening the general population for chronic Q fever is low. A policy of screening known high-risk groups for chronic Q-fever in outbreak areas directly following an outbreak might be more efficient than population screening. A cost-effectiveness analysis should also be performed before initiating a population screening program for chronic Q-fever. PMID- 26132156 TI - Comparing the Age-Friendliness of Different Neighbourhoods Using District Surveys: An Example from Hong Kong. AB - BACKGROUND: To address the age-friendliness of living environment in cities, the World Health Organization (WHO) launched the "Age-friendly cities" (AFC) initiative in 2005. To date, however, no universal standard tool for assessing age-friendliness of a community has been agreed. METHODOLOGY: Two quantitative studies on AFC conducted in two Hong Kong districts-Sha Tin and Tuen Mun-were compared. A total of 801 residents aged >=50 years were interviewed using structured questionnaires based on the WHO's AFC criteria. District-wide differences in age-friendliness were compared on the basis of eight domain scores. Multiple linear regression was used to examine associations with demographic and socio-economic characteristics. The provision of services and amenities was also compared to help explain the difference in domain scores. RESULTS: Variations in mean domain scores were observed in both districts. Sha Tin showed significantly lower scores in outdoor spaces and buildings, transportation, social participation, respect and social inclusion, civic participation and employment, communication and information, as compared with Tuen Mun. Although a significantly higher score on the housing domain was observed in Sha Tin, differences in community and health services domains were insignificant. Socio-demographic factors, such as age group, gender, area of residence, type of housing, experience of elderly care, employment status, self rated health and income, were associated with domain scores. However, variations in services and amenities provision appeared not to be strongly associated with district-wide difference in domain scores. CONCLUSIONS: District differences in public opinions towards age-friendly characteristics were observed in this study. Except for two of the eight domains, Sha Tin had significantly lower scores than Tuen Mun. Some socio-demographic indicators seemed predictive to the differences. Paradoxically, Sha Tin had better services and infrastructure and higher socio economic status, but lower age-friendliness. This warrants detailed research on psychosocial factors that may influence residents' perceptions of local environments. PMID- 26132158 TI - Sequential Insertion Heuristic with Adaptive Bee Colony Optimisation Algorithm for Vehicle Routing Problem with Time Windows. AB - This paper presents a bee colony optimisation (BCO) algorithm to tackle the vehicle routing problem with time window (VRPTW). The VRPTW involves recovering an ideal set of routes for a fleet of vehicles serving a defined number of customers. The BCO algorithm is a population-based algorithm that mimics the social communication patterns of honeybees in solving problems. The performance of the BCO algorithm is dependent on its parameters, so the online (self adaptive) parameter tuning strategy is used to improve its effectiveness and robustness. Compared with the basic BCO, the adaptive BCO performs better. Diversification is crucial to the performance of the population-based algorithm, but the initial population in the BCO algorithm is generated using a greedy heuristic, which has insufficient diversification. Therefore the ways in which the sequential insertion heuristic (SIH) for the initial population drives the population toward improved solutions are examined. Experimental comparisons indicate that the proposed adaptive BCO-SIH algorithm works well across all instances and is able to obtain 11 best results in comparison with the best-known results in the literature when tested on Solomon's 56 VRPTW 100 customer instances. Also, a statistical test shows that there is a significant difference between the results. PMID- 26132157 TI - Remodeling the Dendritic Spines in the Hindlimb Representation of the Sensory Cortex after Spinal Cord Hemisection in Mice. AB - Spinal cord injury (SCI) can induce remodeling of multiple levels of the cerebral cortex system especially in the sensory cortex. The aim of this study was to assess, in vivo and bilaterally, the remodeling of dendritic spines in the hindlimb representation of the sensory cortex after spinal cord hemisection. Thy1 YFP transgenic mice were randomly divided into the control group and the SCI group, and the spinal vertebral plates (T11-T12) of all mice were excised. Next, the left hemisphere of the spinal cord (T12) was hemisected in the SCI group. The hindlimb representations of the sensory cortex in both groups were imaged bilaterally on the day before (0d), and three days (3d), two weeks (2w), and one month (1m) after the SCI. The rates of stable, newly formed, and eliminated spines were calculated by comparing images of individual dendritic spine in the same areas at different time points. In comparison to the control group, the rate of newly formed spines in the contralateral sensory cortex of the SCI group increased at three days and two weeks after injury. The rates of eliminated spines in the bilateral sensory cortices increased and the rate of stable spines in the bilateral cortices declined at two weeks and one month. From three days to two weeks, the stable rates of bilaterally stable spines in the SCI group decreased. In comparison to the control group and contralateral cortex in the SCI group, the re-emerging rate of eliminated spines in ipsilateral cortex of the SCI group decreased significantly. The stable rates of newly formed spines in bilateral cortices of the SCI group decreased from two weeks to one month. We found that the remodeling in the hindlimb representation of the sensory cortex after spinal cord hemisection occurred bilaterally. This remodeling included eliminating spines and forming new spines, as well as changing the reorganized regions of the brain cortex after the SCI over time. Soon after the SCI, the cortex was remodeled by increasing spine formation in the contralateral cortex. Then it was remodeled prominently by eliminating spines of bilateral cortices. Spinal cord hemisection also caused traditional stable spines to become unstable and led the eliminated spines even more hard to recur especially in the ipsilateral cortex of the SCI group. In addition, it also made the new formed spines unstable. PMID- 26132159 TI - Daytime sleep duration and the development of childhood overweight: the KOALA Birth Cohort Study. AB - Reduced nighttime sleep is a risk factor for childhood overweight, but the association between daytime sleep and overweight is unknown. The aim of this study is to evaluate daytime sleep duration as an independent risk factor for childhood overweight. Data from the KOALA Birth Cohort Study on daytime and nighttime sleep at 2 years (N = 2322), and body mass index (BMI) around 2, 5, 6, 7, 8 and 9 years were used. Multivariable general estimating equation regression analyses were performed to examine the associations of sleep duration with BMI (linear) and overweight (logistic). No associations between daytime sleep and BMI or overweight were found, whereas longer nighttime sleep was associated with lower BMI and lower risk of overweight persisting up to age 9. Daytime sleep duration is probably less relevant for prevention of childhood overweight. PMID- 26132160 TI - Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases. AB - Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIalpha. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. On the basis of previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10-100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons. (1) The activity of the metabolites was abrogated by a reducing agent. (2) Compounds inhibited topoisomerase II activity when they were incubated with the enzyme prior to the addition of DNA. (3) Compounds were unable to poison a topoisomerase IIalpha construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIalpha. Several of the extracts enhanced enzyme mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIalpha. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption. PMID- 26132161 TI - Comprehensive Glycomics of a Multistep Human Brain Tumor Model Reveals Specific Glycosylation Patterns Related to Malignancy. AB - Cancer cells frequently express glycans at different levels and/or with fundamentally different structures from those expressed by normal cells, and therefore elucidation and manipulation of these glycosylations may provide a beneficial approach to cancer therapy. However, the relationship between altered glycosylation and causal genetic alteration(s) is only partially understood. Here, we employed a unique approach that applies comprehensive glycomic analysis to a previously described multistep tumorigenesis model. Normal human astrocytes were transformed via the serial introduction of hTERT, SV40ER, H-RasV12, and myrAKT, thereby mimicking human brain tumor grades I-IV. More than 160 glycans derived from three major classes of cell surface glycoconjugates (N- and O glycans on glycoproteins, and glycosphingolipids) were quantitatively explored, and specific glycosylation patterns related to malignancy were systematically identified. The sequential introduction of hTERT, SV40ER, H-RasV12, and myrAKT led to (i) temporal expression of pauci-mannose/mono-antennary type N-glycans and GD3 (hTERT); (ii) switching from ganglio- to globo-series glycosphingolipids and the appearance of Neu5Gc (hTERT and SV40ER); (iii) temporal expression of bisecting GlcNAc residues, alpha2,6-sialylation, and stage-specific embryonic antigen-4, accompanied by suppression of core 2 O-glycan biosynthesis (hTERT, SV40ER and Ras); and (iv) increased expression of (neo)lacto-series glycosphingolipids and fucosylated N-glycans (hTERT, SV40ER, Ras and AKT). These sequential and transient glycomic alterations may be useful for tumor grade diagnosis and tumor prognosis, and also for the prediction of treatment response. PMID- 26132163 TI - Predicting Impacts of Future Climate Change on the Distribution of the Widespread Conifer Platycladus orientalis. AB - Chinese thuja (Platycladus orientalis) has a wide but fragmented distribution in China. It is an important conifer tree in reforestation and plays important roles in ecological restoration in the arid mountains of northern China. Based on high resolution environmental data for current and future scenarios, we modeled the present and future suitable habitat for P. orientalis, evaluated the importance of environmental factors in shaping the species' distribution, and identified regions of high risk under climate change scenarios. The niche models showed that P. orientalis has suitable habitat of ca. 4.2*106 km2 across most of eastern China and identified annual temperature, monthly minimum and maximum ultraviolet B radiation and wet-day frequency as the critical factors shaping habitat availability for P. orientalis. Under the low concentration greenhouse gas emissions scenario, the range of the species may increase as global warming intensifies; however, under the higher concentrations of emissions scenario, we predicted a slight expansion followed by contraction in distribution. Overall, the range shift to higher latitudes and elevations would become gradually more significant. The information gained from this study should be an useful reference for implementing long-term conservation and management strategies for the species. PMID- 26132162 TI - Sortase Enzyme-Mediated Generation of Site-Specifically Conjugated Antibody Drug Conjugates with High In Vitro and In Vivo Potency. AB - Antibody drug conjugates (ADCs) have recently been proven to be highly potent anti-tumor drugs, typically exceeding the efficacy of conventional monoclonal antibodies (mAbs). ADCs are currently produced by chemical conjugation of a small molecule toxin to the mAb through lysine or cysteine side chains. This leads to heterogeneous mixtures of ADCs in which variable numbers of drugs are conjugated to individual antibodies and in which the site of conjugation cannot be defined. Consequently, there is currently significant interest in further development of drug conjugation technologies, with a particular focus on site-specific payload conjugation. Here, we present an enzymatic conjugation platform based on the S. aureus sortase A-mediated transpeptidation reaction, allowing the efficient generation of ADCs with toxins conjugated to pre-defined sites at pre-defined drug-to-antibody ratios. For this, two modifications were introduced: first, immunoglobulin heavy (IgH) and light (IgL) chains were modified at their C termini by addition of the sortase A recognition motif LPETG, and second, the small molecule tubulin polymerization inhibitors monomethylauristatin E (MMAE) and maytansine were modified by addition of a pentaglycine peptide, thus making them suitable substrates for sortase A-mediated transpeptidation. We demonstrate efficient generation and characterization of the anti-CD30 ADC Ac10-vcPAB-MMAE, an enzymatically conjugated counterpart of brentuximab vedotin (Adcetris), as well as several anti-HER-2 ADCs including trastuzumab-maytansine, the counterpart of trastuzumab emtansine (Kadcyla). ADCs generated in this manner were found to display in vitro cell killing activities indistinguishable from the classic conjugates. Further, when tested in vivo in a HER-2-overexpressing ovarian cancer xenograft mouse model, enzymatically generated trastuzumab-maytansine was found to lead to complete regression of established tumors, similar to Kadcyla. PMID- 26132164 TI - Dysgraphia as a Mild Expression of Dystonia in Children with Absence Epilepsy. AB - BACKGROUND: Absence epilepsy (AE) is etiologically heterogeneous and has at times been associated with idiopathic dystonia. OBJECTIVES: Based on the clinical observation that children with AE often exhibit, interictally, a disorder resembling writer's cramp but fully definable as dysgraphia, we tested the hypothesis that in this particular population dysgraphia would represent a subtle expression of dystonia. METHODS: We ascertained the prevalence of dysgraphia in 82 children with AE (mean age 9.7) and average intelligence and compared them with 89 age-, gender- and class-matched healthy children (mean age 10.57) using tests for handwriting fluency and quality, based on which we divided patients and controls into four subgroups: AE/dysgraphia, AE without dysgraphia, controls with dysgraphia and healthy controls. We compared the blink reflex recovery cycle in children belonging to all four subgroups. RESULTS: We identified dysgraphia in 17/82 children with AE and in 7/89 controls (20.7 vs 7.8%; P = 0.016) with the former having a 3.4-times higher risk of dysgraphia regardless of age and gender (odd ratio: 3.49; 95% CI 1.2, 8.8%). The AE/dysgraphia subgroup performed worse than controls with dysgraphia in one test of handwriting fluency (P = 0.037) and in most trials testing handwriting quality (P< 0.02). In children with AE/dysgraphia the blink reflex showed no suppression at short interstimulus intervals, with a difference for each value emerging when comparing the study group with the three remaining subgroups (P<0.001). CONCLUSIONS: In children with AE, dysgraphia is highly prevalent and has a homogeneous, distinctive pathophysiological substrate consistent with idiopathic dystonia. PMID- 26132165 TI - Using a Novel Absolute Ontogenetic Age Determination Technique to Calculate the Timing of Tooth Eruption in the Saber-Toothed Cat, Smilodon fatalis. AB - Despite the superb fossil record of the saber-toothed cat, Smilodon fatalis, ontogenetic age determination for this and other ancient species remains a challenge. The present study utilizes a new technique, a combination of data from stable oxygen isotope analyses and micro-computed tomography, to establish the eruption rate for the permanent upper canines in Smilodon fatalis. The results imply an eruption rate of 6.0 millimeters per month, which is similar to a previously published average enamel growth rate of the S. fatalis upper canines (5.8 millimeters per month). Utilizing the upper canine growth rate, the upper canine eruption rate, and a previously published tooth replacement sequence, this study calculates absolute ontogenetic age ranges of tooth development and eruption in S. fatalis. The timing of tooth eruption is compared between S. fatalis and several extant conical-toothed felids, such as the African lion (Panthera leo). Results suggest that the permanent dentition of S. fatalis, except for the upper canines, was fully erupted by 14 to 22 months, and that the upper canines finished erupting at about 34 to 41 months. Based on these developmental age calculations, S. fatalis individuals less than 4 to 7 months of age were not typically preserved at Rancho La Brea. On the whole, S. fatalis appears to have had delayed dental development compared to dental development in similar-sized extant felids. This technique for absolute ontogenetic age determination can be replicated in other ancient species, including non-saber toothed taxa, as long as the timing of growth initiation and growth rate can be determined for a specific feature, such as a tooth, and that growth period overlaps with the development of the other features under investigation. PMID- 26132166 TI - Functional Activity Limitation and Quality of Life of Leprosy Cases in an Endemic Area in Northeastern Brazil. AB - BACKGROUND: Few studies have evaluated the association between quality of life (QoL) and functional activity limitations (FAL) of leprosy patients as determined by the Screening of Activity Limitation and Safety Awareness scale (SALSA). AIM: To identify the association between FALs and the QoL of patients during and post leprosy treatment. MATERIALS AND METHODS: Cross-sectional survey of 104 patients with leprosy followed in specialist reference centres in Sergipe, Brazil, between June and October 2014. QoL was evaluated using the World Health Organization-QoL BREF (WHOQoL-BREF) questionnaire. The SALSA scale was used to measure FALs. RESULTS: Low SALSA scores were present in 76% of patients. QoL scores were lower for the physical and environmental domains, with median (interquartile range (IQR)) scores of 53.6 (32.1-67.9) and 53.1 (46.9-64.8), respectively. There was a statistical association between increasing SALSA scores and lower QoL as measured by the WHOQoL-BREF. CONCLUSION: Functional limitations are associated with lower QoL in leprosy patients, especially in the physical and environmental WHOQoL-BREF domains. PMID- 26132167 TI - Dosimetric Evaluation of a Simple Planning Technique for Improving Intensity Modulated Radiotherapy for Nasopharyngeal Cancer. AB - PURPOSE: To evaluate the dosimetric outcomes of a simple planning technique for improving intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer (NPC). METHODS: For 39 NPC cases, generally acceptable original plans were generated and were improved by the two planning techniques, respectively: (1) a basal-dose-compensation (BDC) technique, in which the treatment plans were re optimized based on the original plans; (2) a local-dose-control (LDC) technique, in which the original plans were re-optimized with constraints for hot and cold spots. The BDC, original, and LDC plans were then compared regarding homogeneity index (HI) and conformity index (CI) of planning target volumes (PTVs), organ-at risk (OAR) sparing and monitor units (MUs) per fraction. The whole planning times were also compared between the BDC and LDC plans. RESULTS: The BDC plans had superior HIs / CIs, by 13-24% / 3-243%, respectively, over the original plans. Compared to the LDC plans, the BDC plans provided better HIs only for PTVnx (the PTV of nasopharyngeal primary tumor) by 11% and better CIs for all PTVs by 2 134%. The BDC technique spared most OARs, by 1-9%. The average MUs of the BDC, original, and LDC plans were 2149, 2068 and 2179, respectively. The average whole planning times were 48 and 69 minutes for the BDC and LDC plans, respectively. CONCLUSIONS: For the IMRT of nasopharyngeal cancer, the BDC planning technique can improve target dose homogeneity, conformity and OAR sparing, with better planning efficiency. PMID- 26132168 TI - Correction: Bacillus subtilis KCTC 11782BP-Produced Alginate Oligosaccharide Effectively Suppresses Asthma via T-Helper Cell Type 2-Related Cytokines. AB - [This corrects the article DOI: 10.1371/journal.pone.0117524.]. PMID- 26132170 TI - Persistence of racial disparities in prescription of first-generation antipsychotics in the USA. AB - PURPOSE: The aim of this study was to estimate the prevalence of first-generation antipsychotics (FGA) prescribed for treatment of psychiatric and neurological conditions and use of benztropine to reduce extrapyramidal side effects (EPS) by patient race/ethnicity in a nationally representative sample of adult outpatient visits. METHODS: The study sample included all outpatient visits (N = 8154) among patients aged 18-69 years where a prescription for one or more antipsychotics was recorded across 6 years of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (2005-2010). Use of FGA was compared by race/ethnicity using multiple logistic regression models accounting for patient and clinical characteristics stratified by neighborhood poverty rate. Frequency of EPS was determined by use of benztropine to reduce or prevent EPS. RESULTS: Black patients were significantly more likely than White patients to use FGA (odds ratio = 1.48, p = 0.040) accounting for psychiatric and neurological diagnoses, treatment setting, metabolic factors, neighborhood poverty, and payer source. Black patients were more than twice as likely as White patients to receive higher-potency FGA (haloperidol or fluphenazine), particularly in higher poverty areas (odds ratio = 2.50, p < 0.001). Use of FGA, higher among Black than White patients, was positively associated with use of benztropine to reduce EPS. CONCLUSIONS: Racial disparities in the pharmacological treatment of severe mental disorders persist 30 years after the introduction of second-generation antipsychotics. The relatively high frequency of FGA of use among Black patients compared with White patients despite more Food and Drug Administration-approved indications and lower EPS risk for second-generation antipsychotics requires additional research. PMID- 26132172 TI - Rhythmic Aortic Contractions Induced by Electrical Stimulation In Vivo in the Rat. AB - For over a century, the behavior of the aorta and other large arteries has been described as passive elastic tubes in which no active contraction occurs in the smooth muscle wall. In response to pulsatile pressure changes, the vessels undergo a 'passive' elastic dilatation-contraction cycle, described as a "Windkessel" effect. However, Mangel and colleagues have presented evidence that is contrary to this view. They reported that in the rabbit, the aorta undergoes rhythmic 'active' (contraction) during the cardiac cycle; but these findings have been largely ignored. In the present study, we observed spontaneous contractions in synchrony with the heartbeat in another species (rat). In addition we demonstrate that aorta contractions are of neurogenic origin. Electrical stimulation of the aorta evoked contractions that occur at a rate that is in the range of the animal's heartbeat and are suppressed by tetrodotoxin and the alpha adrenergic receptor blocker, phentolamine. Altogether, these findings indicate that aortic contractions are under neural control from the heart. PMID- 26132171 TI - Capillary Isoelectric Focusing Immunoassay for Fat Cell Differentiation Proteomics. AB - Profiling cellular proteome is critical to understanding signal integration during cell fate determination. In this study, the capability of capillary isoelectric focusing (cIEF) immunoassays to detect post-translational modifications (PTM) of protein isoforms is demonstrated. cIEF immunoassays exhibit protein detection sensitivity at up to 5 orders of magnitude higher than traditional methods. This detection ultra-sensitivity permits proteomic profiling of several nanograms of tissue samples. cIEF immunoassays are employed to simultaneously profile three protein kinases during fat cell differentiation: cGMP-dependent protein kinase type I (PKG-I) of the nitric oxide (NO) signaling pathway, protein kinase B (Akt) of the insulin signaling pathway, and extracellular signal-regulated kinase (ERK) of the mitogen-activated protein kinase (MAPK) signaling pathway. Interestingly, a switch in the expression level of PKG- isoforms is observed during fat cell differentiation. While both PKG Ialpha and PKG-Ibeta isoforms are present in preadipocytes, only PKG-Ibeta isoform is expressed in adipocytes. On the other hand, the phosphorylation level increases for Akt while decreases for ERK1 and ERK2 following the maturation of preadipocytes into adipocytes. Taken together, cIEF immunoassay provides a highly sensitive means to study fat cell differentiation proteomics. cIEF immunoassay should be a powerful proteomics tool to study complex protein signal integration in biological systems. PMID- 26132173 TI - An Academic Support Strategy: The "Magic Pencil". PMID- 26132174 TI - Avatar Case Studies: A Learning Activity to Bridge the Gap Between Classroom and Clinical Practice in Nursing Education. PMID- 26132176 TI - Flow Cytometry of Extracellular Vesicles: Potential, Pitfalls, and Prospects. AB - Evidence suggests that extracellular vesicles (EVs) can play roles in physiology and pathology, providing impetus to explore their use as diagnostic and therapeutic targets. However, EVs are also small, heterogeneous, and difficult to measure, and so this potential has not yet been realized. The development of improved approaches to EV detection and characterization will be critical to further understanding their roles in physiology and disease. Flow cytometry has been a popular tool for measuring cell-derived EVs, but has often been used in an uncritical manner in which fundamental principles and limitations of the instrument are ignored. Recent efforts to standardize procedures and document the effects of different methodologies have helped to address this shortcoming, but much work remains. In this paper, I address some of the instrument, reagent, and analysis considerations relevant to measurement of individual EVs in flow, with the aim of clarifying a path to quantitative and standardized measurement of these interesting and potentially important biological nanoparticles. PMID- 26132175 TI - Visualization of Telomere Integrity and Function In Vitro and In Vivo Using Immunofluorescence Techniques. AB - In cancer cells, telomere length maintenance occurs largely via the direct synthesis of TTAGGG repeats at chromosome ends by telomerase, or less frequently by the recombination-dependent alternative lengthening of telomeres (ALT) pathway. The latter is characterized by the atypical clustering of telomeres within promyelocytic leukemia (PML) nuclear bodies, which harbor proteins that are linked with DNA repair and recombination activity. For this reason, it is speculated that these associated PML bodies represent the sites of the recombination that maintains telomere length. The protocols described here can be employed for the routine investigation of the structural integrity of telomeres and the association of proteins at telomeres in normal cells, challenged cells, and archived formalin-fixed paraffin-embedded clinical tissue specimens that may have activated the ALT pathway. PMID- 26132169 TI - Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High Density Imputation. AB - Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency >=0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated. PMID- 26132177 TI - Collection, Storage, and Preparation of Human Blood Cells. AB - Human peripheral blood is often studied by flow cytometry in both the research and clinical laboratories. The methods for collection, storage, and preparation of peripheral blood will vary depending on the cell lineage to be examined as well as the type of assay to be performed. This unit presents protocols for collection of blood, separation of leukocytes from whole blood by lysis of erythrocytes, isolating mononuclear cells by density gradient separation, and assorted non-flow sorting methods, such as magnetic bead separations, for enriching specific cell populations, including monocytes, T lymphocytes, B lymphocytes, neutrophils, and platelets, prior to flow cytometric analysis. A protocol is also offered for cryopreservation of cells, since clinical research often involves retrospective flow cytometric analysis of samples stored over a period of months or years. PMID- 26132178 TI - High Throughput-Based Mitochondrial Function Assays by Multi-Parametric Flow Cytometry. AB - Mitochondrial dysfunction has been increasingly implicated as an important mechanism for chemical-induced toxicity. In the present unit, we describe a multi parametric flow cytometry assay to assess the effects of drug or chemical-induced mitochondrial dysfunction in cells. Cells are cultured in a glucose-supplemented medium and exposed to increasing concentrations of various chemicals. Several key mitochondrial/cellular parameters known to be directly impacted by mitochondrial dysfunction, such as mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (ROS) production, intracellular reduced glutathione (GSH) level, and cell viability, are simultaneously measured by flow cytometry. PMID- 26132180 TI - Caring for women in their post reproductive life: current recommendations on hormone replacement therapy. PMID- 26132181 TI - Epidemiology of goitre in Sri Lanka in the post-iodization era. AB - INTRODUCTION: Previous studies of goitre in Sri Lanka proposed the presence of a goitre belt, which was refuted subsequently. Epidemiology of goitre in the post iodization era needs re-evaluation. Objectives To describe the epidemiology of goitre in Sri Lanka. METHODS: A descriptive cross-sectional study was conducted in designated zones except in conflict areas in 2006/2007. An interviewer administered questionnaire was used and patients were evaluated clinically, biochemically and cytologically. RESULTS: Among 5200 participans 426 had goitre. Mean age was 36.3 (SD 17.3) years. Goitre was commonest in the age group 40-49 years with a female pre-ponderance. The prevalence was similar in all zones with pockets of high prevalence in each zone. Overall islandwide adjusted prevalence was 6.8% (95% CI = 6.0-7.6). CONCLUSIONS: There was no identifiable goitre belt.There were pockets of high prevalence in all zones. Goitre remains a public health issue despite universal iodization. PMID- 26132182 TI - Auxological outcome of growth hormone therapy at cessation of treatment in a cohort of growth hormone deficient Sri Lankan patients. AB - INTRODUCTION: Recombinant human growth hormone (r-hGH) for growth hormone deficiency (GHD) has been available free in the state hospitals of Sri Lanka since 2009. OBJECTIVES: The aims were to compare height standard deviation scores (SDS) before and after treatment and compare heights at final assessment in relation to the target height (TH) and TH range. METHODS: Patients with confirmed GHD followed up at the University Unit of the Lady Ridgeway Hospital, Colombo were studied. Anthropometric data were prospectively recorded from presentation to cessation of therapy. The height SDS before and after treatment were calculated and the heights at final assessment were compared with the TH and TH range. RESULTS: Sixteen patients (15 boys) had completed treatment. The mean age at diagnosis was 145.38 (SD=34.28) months with a mean skeletal age of 97.5 (SD=42.85) months. Mean ages at commencement was 164.75 (SD=36.81) months and at cessation of therapy 212.06 (SD=30.12) months duration of therapy was 47.31 (SD=23.99) months.Majority had isolated GHD and 8 patients had pituitary hypoplasia on neuro-imaging. The height SDS improved significantly with treatment from -4.438 (1.18) to -3.37 (0.81), p<0.001. When finally assessed at ages ranging from 15 years 10 months to 26 years 9 months, one patient had reached the TH while six were in the TH range. CONCLUSIONS: Auxological response to therapy was significant although treatment was started late due to financial constraints. PMID- 26132183 TI - A comparison of endometrial thickness following augmentation of ovulation with clomifene citrate or letrozole in women with ovulatory infertility. AB - OBJECTIVES: To compare endometrial thickness following augmentation of ovulation with clomifene (CC) and letrozole and to assess the rate of multi-follicle development and the FSH fluctuations during the stimulated cycles. METHODS: A comparative study was carried out at the infertility clinic of Faculty of Medicine, University of Kelaniya, Sri Lanka. Each arm included 25 participants. They received either 100 mg of CC or 2.5 mg of letrozole per day for 5 days starting from 2nd day of the cycle. The fluctuation of FSH in the follicular phase of the cycle, the endometrial thickness and the number of pre-ovulatory follicles on the day of detecting a mature follicle, were measured. RESULTS: Treatment with letrozole resulted in a smaller rise in the follicular phase FSH, which was shorter in duration than with CC. Also it resulted in a higher mean endometrial thickness at the time of detecting a mature follicle [9.89 (SD=2.02) mm vs. 8.58 (SD=1.32) mm; p=0.021]. Augmentation of ovulation with CC showed a trend towards multi-follicle development compared to letrozole. CONCLUSIONS: This study suggests that letrozole is superior to CC in augmentation of ovulation in terms of endometrial growth and mono-follicle development. However more studies are needed to assess how these differences affect the treatment outcome before it is recommended for clinical use. PMID- 26132184 TI - Environmental and occupational exposures as a cause of male infertility. AB - OBJECTIVES: To determine the association between environmental and occupational exposures, semen parameters and lead (Pb) and cadmium (Cd) levels in seminal plasma of men investigated for infertility. METHODS: Data were collected from 300 men investigated for infertility using an interviewer administered questionnaire. Seminal fluid analysis and classification was done according to WHO guidelines. Positive exposure was defined as environmental or occupational exposure to agro or industrial chemicals, heavy metals and living in areas within 50 m of potential sources of pollution for three months or more. Seminal plasma lead and cadmium levels were estimated by graphite furnace atomic absorption spectrophotometry after digestion with nitric acid. The means of sperm parameters, Pb and Cd concentrations between exposed and non exposed groups were compared using t-test. RESULTS: Mean age was 34.8 (95% CI 34.2-35.4) years BMI was 24.3 (95% CI 23.8-24.7) kg/m2 and duration of the infertility was 45.7 (41.7 49.6) months. In this study, 54.6% were exposed to toxins through environmental or occupational sources. All sperm parameters were lower in the exposed group when compared to the non exposed. Lead and cadmium were detected in 38.3% and 23% of men respectively. The distance from the source of possible environmental or occupational exposure was negatively correlated to seminal plasma Pb (r=0.06, p>0.05) and Cd (r=0.26, p<0.05) concentrations. In the exposed, mean lead concentration was 17.7 (95% CI 15.0-20.4) MUg/dl and 13.5 (95% CI 11.2-15.7) MUg/dl in non exposed and cadmium concentration in exposed was 1.2 (95% CI 1.1 1.4) MUg/dl and 1.1 (0.9-1.3) MUg/dl in non-exposed. CONCLUSIONS: Environmental and occupational exposures were associated with reduced sperm count motility, viability, normal forms and detectable levels of lead and cadmium in seminal plasma. PMID- 26132185 TI - Effect of different cooking methods on glycaemic index of Indian and Pakistani basmati rice varieties. AB - INTRODUCTION: Glycaemic index (GI) reflects the blood glucose response after ingestion of a 50 g digestible carbohydrate portion. Many factors affect the GI, including degree of starch gelatinization. METHODS: The objective was to determine the GI and the effect of different cooking methods on GI of a Pakistani basmati rice (PBR) and an Indian basmati rice (IBR) frequently purchased by Sri Lankans. This was a crossover study. Participants were ten healthy individuals aged 20-30 years whose BMI range was 18.5-23.5 kgm(-2). Proximate composition, [carbohydrate, protein, fat, soluble dietary fibre (SDF), insoluble dietary fibre (IDF) and ash], amylose content and GI of the two rice varieties were determined by using standard methods. Rice was cooked separately in a rice cooker and a microwave by adding 1 cup of rice (110 g) and 1 cup of water (150 ml)). Glucose was used as the standard. GI values were expressed as the average value of 10 participants. RESULTS: Fat, total dietary fibre (TDF), SDF and IDF contents were significantly (p<0.05) higher in IBR when compared to PBR. The GI values of IBR and PBR cooked in a rice cooker (GI=54 SD=8; GI=64 SD=12) or microwave (GI=43 SD=28; GI=56 SD=12) belonged to low and medium GI categories respectively. A percentage reduction in GI values was seen in PBR (12.5%) and IBR (20.4%) when cooked in a microwave oven compared to a rice cooker. CONCLUSIONS: Irrespective of the method of cooking PBR had medium GI and IBR had low GI. PMID- 26132186 TI - Genotypes of hepatitis B virus identified in patients tested prior to endoscopy from a Teaching Hospital in the Central Province of Sri Lanka. AB - The present study was carried out to identify the hepatitis B virus (HBV) genotypes in six patients attending the surgical clinic who were positive for hepatitis B surface antigen. DNA was extracted from the serum of patients and subjected to a modified nested PCR to detect a 585 bp region within the S gene of the HBV genome. Positive PCR products were purified and sequenced via a cycle sequencing method. The sequence data were analyzed with reference sequences in the HepSEQ database to identify the particular HBV genotype of the samples. Nested PCR for the S gene of the HBV genome was positive in 2 out of 6 samples. The genotyping and sequence analysis of the PCR products showed HBV genotype A with a homology of 98% to the reference sequences in the HepSeq database. PMID- 26132187 TI - Accidental methyl salicylate poisoning in two adults. PMID- 26132188 TI - Survival of a patient after self-injection of paraquat and surgical excision of the injection site. PMID- 26132189 TI - Isolated coccygeal tuberculosis. PMID- 26132190 TI - Pulmonary fibrosis with cholesterol granulomata in a patient working in a fireworks factory. PMID- 26132191 TI - Antiphospholipid syndrome in a man presenting with cold autoimmune haemolytic anaemia. PMID- 26132192 TI - Successful management of a pregnancy complicated by essential thrombocythaemia with pegylated interferon. PMID- 26132193 TI - Allogeneic bone marrow transplant in a child with thalassaemia. PMID- 26132194 TI - Re: Outcome of retrograde ureteric stenting as a urinary drainage procedure in ureteric obstruction related to malignant lesions. PMID- 26132195 TI - miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells. AB - CD82/KAI1, a member of the tetraspanin superfamily, is a suppressor of metastasis and CD82 inhibits canonical Wnt signaling via downregulation of several Frizzled (FZD) isoforms, resulting in accumulation of beta-catenin at the cell membrane. In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs). The miRanda algorithm predicted 11 miRNAs from FZD sequences. Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells. Transfection with miR-203 and miR338 3p mimics or inhibitors revealed that miR-203 downregulated FZD2 mRNA (by 0.268 fold) and protein expression (by 0.701-fold). Moreover, transfection with the miR 203 mimic also inhibited cell migration. Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway. PMID- 26132196 TI - Genetic Basis and Functional Consequences of Differential Expression of the CmeABC Efflux Pump in Campylobacter jejuni Isolates. AB - The CmeABC multidrug efflux transporter of Campylobacter jejuni plays a key role in antimicrobial resistance and is suppressed by CmeR, a transcriptional regulator of the TetR family. Overexpression of CmeABC has been observed in laboratory-generated mutants, but it is unknown if this phenotype occurs naturally in C. jejuni isolates and if it has any functional consequences. To answer these questions, expression of cmeABC in natural isolates obtained from broiler chickens, turkeys and humans was examined, and the genetic mechanisms and role of cmeABC differential expression in antimicrobial resistance was determined. Among the 64 C. jejuni isolates examined in this study, 43 and 21 were phenotypically identified as overexpression (OEL) and wild-type expression (WEL) levels. Representative mutations of the cmeABC promoter and/or CmeR-coding sequence were analyzed using electrophoretic mobility shift assays and transcriptional fusion assays. Reduced CmeR binding to the mutated cmeABC promoter sequences or decreased CmeR levels increased cmeABC expression. Several examined amino acid substitutions in CmeR did not affect its binding to the cmeABC promoter, but a mutation that led to C-terminal truncation of CmeR abolished its DNA-binding activity. Interestingly, some OEL isolates harbored no mutations in known regulatory elements, suggesting that cmeABC is also regulated by unidentified mechanisms. Overexpression of cmeABC did not affect the susceptibility of C. jejuni to most tested antimicrobials except for chloramphenicol, but promoted the emergence of ciprofloxacin-resistant mutants under antibiotic selection. These results link CmeABC overexpression in natural C. jejuni isolates to various mutations and indicate that this phenotypic change promotes the emergence of antibiotic-resistant mutants under selection pressure. Thus, differential expression of CmeABC may facilitate Campylobacter adaptation to antibiotic treatments. PMID- 26132197 TI - Refining Trait Resilience: Identifying Engineering, Ecological, and Adaptive Facets from Extant Measures of Resilience. AB - The current paper presents a new measure of trait resilience derived from three common mechanisms identified in ecological theory: Engineering, Ecological and Adaptive (EEA) resilience. Exploratory and confirmatory factor analyses of five existing resilience scales suggest that the three trait resilience facets emerge, and can be reduced to a 12-item scale. The conceptualization and value of EEA resilience within the wider trait and well-being psychology is illustrated in terms of differing relationships with adaptive expressions of the traits of the five-factor personality model and the contribution to well-being after controlling for personality and coping, or over time. The current findings suggest that EEA resilience is a useful and parsimonious model and measure of trait resilience that can readily be placed within wider trait psychology and that is found to contribute to individual well-being. PMID- 26132198 TI - Virulence profile: Leonard Mermel. PMID- 26132199 TI - Microwave Accelerated Green Synthesis of Stable Silver Nanoparticles with Eucalyptus globulus Leaf Extract and Their Antibacterial and Antibiofilm Activity on Clinical Isolates. AB - A simple and rapid microwave assisted method of green synthesis of silver nanoparticles (AgNPs) was developed using aqueous leaf extract of Eucalyptus globulus(ELE), and their antibacterial and antibiofilm potential investigated. With this aim, the aqueous solutions of ELE and AgNO3(1 mM) were mixed (1:4 v/v), and microwave irradiated at 2450 Mhz, for 30 sec. The instant color change of the ELE-AgNO3 mixture from pale yellow to dark brown indicated ELE-AgNPs synthesis. The intensity of peak at 428 nm in UV-Vis spectra, due to the surface plasmon resonance of AgNPs, varied with the amount of ELE, AgNO3 concentration, pH and time of incubation. The biosynthesized ELE-AgNPs were characterized by UV-visible spectroscopy, XRD, TEM, SEM-EDX, FTIR and TGA analyses. The size of ELE-AgNPs was determined to be in range of 1.9-4.3 nm and 5-25 nm, with and without microwave treatment, respectively. SEM exhibited the capping of AgNPs with the ELE constituents, and validated by FTIR analysis. The FTIR data revealed the presence of plant organic constituents and metabolites bound to ELE-AgNPs, which contributes for their stability. The antimicrobial activity of ELE-AgNPs was assessed by growth and biofilm inhibition of extended spectrum beta-lactamase (ESBL) producing Pseudomonas aeruginosa, Escherichia coli and methicillin resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) clinical bacterial isolates. The results demonstrated that S. aureus were more sensitive to ELE-AgNPs than E. coli and P. aeruginosa. MRSA exhibited higher sensitive than MSSA, whereas P. aeruginosa were more sensitive than E. coli to ELE-AgNPs treatment. Also, significant (83 +/- 3% and 84 +/- 5%) biofilm inhibition was observed in case of S. aureus and P. aeruginosa, respectively. The results elucidated environmentally friendly, economical and quick method for production of colloidal bio-functionalized ELE-AgNPs, for effectual clinical applications, as broad spectrum antibacterial agents and biofilm inhibitors. PMID- 26132200 TI - Risk of Criminal Victimisation in Outpatients with Common Mental Health Disorders. AB - BACKGROUND: Crime victimisation is a serious problem in psychiatric patients. However, research has focused on patients with severe mental illness and few studies exist that address victimisation in other outpatient groups, such as patients with depression. Due to large differences in methodology of the studies that address crime victimisation, a comparison of prevalence between psychiatric diagnostic groups is hard to make. Objectives of this study were to determine and compare one-year prevalence of violent and non-violent criminal victimisation among outpatients from different diagnostic psychiatric groups and to examine prevalence differences with the general population. METHOD: Criminal victimisation prevalence was measured in 300 outpatients living in Amsterdam, The Netherlands. Face-to-face interviews were conducted with outpatients with depressive disorder (n = 102), substance use disorder (SUD, n = 106) and severe mental illness (SMI, n = 92) using a National Crime Victimisation Survey, and compared with a matched general population sample (n = 10865). RESULTS: Of all outpatients, 61% reported experiencing some kind of victimisation over the past year; 33% reported violent victimisation (3.5 times more than the general population) and 36% reported property crimes (1.2 times more than the general population). Outpatients with depression (67%) and SUD (76%) were victimised more often than SMI outpatients (39%). Younger age and hostile behaviour were associated with violent victimisation, while being male and living alone were associated with non-violent victimisation. Moreover, SUD was associated with both violent and non-violent victimisation. CONCLUSION: Outpatients with depression, SUD, and SMI are at increased risk of victimisation compared to the general population. Furthermore, our results indicate that victimisation of violent and non-violent crimes is more common in outpatients with depression and SUD than in outpatients with SMI living independently in the community. PMID- 26132201 TI - Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium. AB - BACKGROUND: The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses. METHODOLOGY/PRINCIPAL FINDINGS: We studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035). CONCLUSION: Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future. PMID- 26132202 TI - mTOR Directs Breast Morphogenesis through the PKC-alpha-Rac1 Signaling Axis. AB - Akt phosphorylation is a major driver of cell survival, motility, and proliferation in development and disease, causing increased interest in upstream regulators of Akt like mTOR complex 2 (mTORC2). We used genetic disruption of Rictor to impair mTORC2 activity in mouse mammary epithelia, which decreased Akt phosphorylation, ductal length, secondary branching, cell motility, and cell survival. These effects were recapitulated with a pharmacological dual inhibitor of mTORC1/mTORC2, but not upon genetic disruption of mTORC1 function via Raptor deletion. Surprisingly, Akt re-activation was not sufficient to rescue cell survival or invasion, and modestly increased branching of mTORC2-impaired mammary epithelial cells (MECs) in culture and in vivo. However, another mTORC2 substrate, protein kinase C (PKC)-alpha, fully rescued mTORC2-impaired MEC branching, invasion, and survival, as well as branching morphogenesis in vivo. PKC-alpha-mediated signaling through the small GTPase Rac1 was necessary for mTORC2-dependent mammary epithelial development during puberty, revealing a novel role for Rictor/mTORC2 in MEC survival and motility during branching morphogenesis through a PKC-alpha/Rac1-dependent mechanism. PMID- 26132203 TI - Sociocultural and Demographic Risk Factors for the Development of Multiple Sclerosis in Kuwait: A Case - Control Study. AB - INTRODUCTION: Immunological, genetic and environmental factors are believed to play important roles in the pathogenesis of Multiple Sclerosis (MS). There have been many studies on risk factors for MS but these have been mainly in Caucasian populations; robust studies in Arab populations remain relatively uncommon. This study therefore aimed to identify behavioral, socio-cultural, and demographic factors associated with development of MS in Kuwait, a high income Arab country, currently undergoing a demographic transition. SUBJECTS AND METHODS: In this case control study, 195 Kuwaiti MS patients and 146 healthy age and sex-matched controls were recruited. Both groups of subjects were interviewed using a structured questionnaire, in relation to anthropometric, socio-cultural and demographic data, residence during the 1990/91 Gulf War and current and past medical history, including medications. We also clinically evaluated, and retrospectively reviewed medical records of patients to derive appropriate clinical information, including associated chronic medical illness requiring long term treatment. RESULTS: On multiple logistic regression analysis after adjustment for potential confounders including age, gender and BMI, in all the subjects, a positive associations prevail with presence of MS and some sociocultural and demographic factors, which included non-Bedouin ethnicity (AOR 2, 95% CI 1.0-3.9, p 0.049), positive family history of MS (AOR 10.6, 95% CI 3.0 36.9), p < 0.001), and low daily sunlight exposure of < 15min/day (AOR 5.3, 95% CI 2.7-10.5 p < 0.001). In addition, while 41.8% of MS patients indicated at least one comorbidity, only 26.8% of the controls reported any associated physical illness, with the suggestion that presence of certain comorbidities might increase MS risk (AOR 2.4, 95% CI 1.3-4.7, p < 0.001). Other risk variables such as smoking status and mode of routine outdoor dressing were not significant in all the MS subjects taken as a whole, but demonstrated variably positive associations in the MS subgroup classified as those with established disease and those who were newly diagnosed and drug naive. CONCLUSIONS: This study suggests that a positive family history of MS and presence of certain comorbidities appeared to be associated with an increased risk of developing MS. In contrast, relatively increased amount of daily sunlight exposure and Bedouin ethnicity appear to somewhat be protective. It is speculated that the relationship of sunlight exposure with MS might be due to vitamin D availability, and is deserving of further study. PMID- 26132204 TI - Linking GPS Telemetry Surveys and Scat Analyses Helps Explain Variability in Black Bear Foraging Strategies. AB - Studying diet is fundamental to animal ecology and scat analysis, a widespread approach, is considered a reliable dietary proxy. Nonetheless, this method has weaknesses such as non-random sampling of habitats and individuals, inaccurate evaluation of excretion date, and lack of assessment of inter-individual dietary variability. We coupled GPS telemetry and scat analyses of black bears Ursus americanus Pallas to relate diet to individual characteristics and habitat use patterns while foraging. We captured 20 black bears (6 males and 14 females) and fitted them with GPS/Argos collars. We then surveyed GPS locations shortly after individual bear visits and collected 139 feces in 71 different locations. Fecal content (relative dry matter biomass of ingested items) was subsequently linked to individual characteristics (sex, age, reproductive status) and to habitats visited during foraging bouts using Brownian bridges based on GPS locations prior to feces excretion. At the population level, diet composition was similar to what was previously described in studies on black bears. However, our individual-based method allowed us to highlight different intra-population patterns, showing that sex and female reproductive status had significant influence on individual diet. For example, in the same habitats, females with cubs did not use the same food sources as lone bears. Linking fecal content (i.e., food sources) to habitat previously visited by different individuals, we demonstrated a potential differential use of similar habitats dependent on individual characteristics. Females with cubs-of-the-year tended to use old forest clearcuts (6-20 years old) to feed on bunchberry, whereas females with yearling foraged for blueberry and lone bears for ants. Coupling GPS telemetry and scat analyses allows for efficient detection of inter-individual or inter-group variations in foraging strategies and of linkages between previous habitat use and food consumption, even for cryptic species. This approach could have interesting ecological implications, such as supporting the identification of habitats types abundant in important food sources for endangered species targeted by conservation measures or for management actions for depredating animals. PMID- 26132205 TI - Sharing with More Caring: Coordinating and Improving the Ethical Governance of Data and Biomaterials Obtained from Children. AB - INTRODUCTION: Research on complex health conditions such as neurodevelopmental disorders increasingly relies on large-scale research and clinical studies that would benefit from data sharing initiatives. Organizations that share data stand to maximize the efficiency of invested research dollars, expedite research findings, minimize the burden on the patient community, and increase citation rates of publications associated with the data. OBJECTIVE: This study examined ethics and governance information on websites of databases involving neurodevelopmental disorders to determine the availability of information on key factors crucial for comprehension of, and trust and participation in such initiatives. METHODS: We identified relevant databases identified using online keyword searches. Two researchers reviewed each of the websites and identified thematic content using principles from grounded theory. The content for each organization was interrogated using the gap analysis method. RESULTS: Sixteen websites from data sharing organizations met our inclusion criteria. Information about types of data and tissues stored, data access requirements and procedures, and protections for confidentiality were significantly addressed by data sharing organizations. However, special considerations for minors (absent from 63%), controls to check if data and tissues are being submitted (absent from 81%), disaster recovery plans (absent from 81%), and discussions of incidental findings (absent from 88%) emerged as major gaps in thematic website content. When present, content pertaining to special considerations for youth, along with other ethics guidelines and requirements, were scattered throughout the websites or available only from associated documents accessed through live links. CONCLUSION: The complexities of sharing data acquired from children and adolescents will only increase with advances in genomic and neuro science. Our findings suggest that there is a need to improve the consistency, depth and accessibility of governance and policies on which these collaborations can lean specifically for vulnerable young populations. PMID- 26132207 TI - Electrochemical Control of Rapid Bioorthogonal Tetrazine Ligations for Selective Functionalization of Microelectrodes. AB - We demonstrate that bioorthogonal tetrazine ligations can be utilized to rapidly modify electrode surfaces, both with redox probes and enzymes. Furthermore, we show that the redox-active nature of 1,2,4,5-tetrazines can be exploited to gain electrochemical control over surface modification. To our knowledge this is the first demonstration of controlling a tetrazine ligation by changing the redox state of one of the reactants. We utilize the redox-switchable feature of tetrazine ligations for the site-selective functionalization of a 10 MUm spaced interdigitated array of microelectrodes. In addition, we were able to achieve potential controlled ligation of the redox enzyme horseradish peroxidase to a macroscopic planar electrode. The rapid kinetics, bioorthogonal reactivity, and electrochemical control provided by tetrazine ligations should lead to numerous applications related to electrode functionalization. PMID- 26132206 TI - Seasonality of Pneumococcal Nasopharyngeal Carriage in Rural Gambia Determined within the Context of a Cluster Randomized Pneumococcal Vaccine Trial. AB - BACKGROUND: We conducted an ancillary study among individuals who had participated in a PCV-7 trial in rural Gambia, to determine the influence of season on the prevalence of pneumococcal carriage. METHODS: 636 individuals above 30 months of age were followed from 4 to 20 months after vaccination with PCV-7 or meningococcal-conjugate-vaccine. Nasopharyngeal swabs were collected periodically between November 2006 and June 2008. Overall, 4,495 NPS were collected. RESULTS: Prevalence of pneumococcal nasopharyngeal carriage in the study subjects (median age 11 years) was 55.0%; this prevalence decreased linearly with increasing age (p = 0.001). Prevalence of carriage was significantly higher during the dry than the rainy season for any pneumococcal carriage [57.6% versus 47.8% (p<0.001)], pneumococcal vaccine serotype carriage [10.3% versus 6.5% (p< 0.001)] and non-vaccine serotype carriage [49.7% versus 42.7% (p<0.001)]. Differences remained significant in the adjusted analysis. CONCLUSIONS: In areas of Africa with marked variation in rainfall, seasonality of pneumococcal carriage needs to be considered when interpreting carriage data. PMID- 26132208 TI - The increase in serum 25-hydroxyvitamin D following weight loss does not contribute to the improvement in insulin sensitivity, insulin secretion and beta cell function. AB - Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (beta-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI >= 27 kg/m(2) were divided based on weight loss at 1 year: < 5% (non-responders, n 56) and >= 5% (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9.5% of their weight when compared with non-responders who lost only 0.8% of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P = 0.0003) and disposition index (P = 0.02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8.9 (SD 12.5) v. 3.6 (SD 10.7) nmol/l, P = 0.05). However, it had not been associated with amelioration of insulin sensitivity and beta-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or beta cell function. PMID- 26132210 TI - Brain responds to another person's eye blinks in a natural setting-the more empathetic the viewer the stronger the responses. AB - An observer's brain is known to respond to another person's small nonverbal signals, such as gaze shifts and eye blinks. Here we aimed to find out how an observer's brain reacts to a speaker's eye blinks in the presence of other audiovisual information. Magnetoencephalographic brain responses along with eye gaze were recorded from 13 adults who watched a video of a person telling a story. The video was presented first without sound (visual), then with sound (audiovisual), and finally the audio story was presented with a still-frame picture on the screen (audio control). The viewers mainly gazed at the eye region of the speaker. Their saccades were suppressed at about 180 ms after the start of the speaker's blinks, a subsequent increase of saccade occurence to the base level, or higher, at around 340 ms. The suppression occurred in visual and audiovisual conditions but not during the control audio presentation. Prominent brain responses to blinks peaked in the viewer's occipital cortex at about 250 ms, with no differences in mean peak amplitudes or latencies between visual and audiovisual conditions. During the audiovisual, but not visual-only, presentation, the responses were the stronger the more empathetic the subject was according to the Empathic Concern score of the Interpersonal Reactivity Index questionnaire (Spearman's rank correlation, 0.73). The other person's eye blinks, nonverbal signs that often go unnoticed, thus elicited clear brain responses even in the presence of attention-attracting audiovisual information from the narrative, with stronger responses in people with higher empathy scores. PMID- 26132209 TI - Uranium Biominerals Precipitated by an Environmental Isolate of Serratia under Anaerobic Conditions. AB - Stimulating the microbially-mediated precipitation of uranium biominerals may be used to treat groundwater contamination at nuclear sites. The majority of studies to date have focussed on the reductive precipitation of uranium as U(IV) by U(VI) and Fe(III)-reducing bacteria such as Geobacter and Shewanella species, although other mechanisms of uranium removal from solution can occur, including the precipitation of uranyl phosphates via bacterial phosphatase activity. Here we present the results of uranium biomineralisation experiments using an isolate of Serratia obtained from a sediment sample representative of the Sellafield nuclear site, UK. When supplied with glycerol phosphate, this Serratia strain was able to precipitate 1 mM of soluble U(VI) as uranyl phosphate minerals from the autunite group, under anaerobic and fermentative conditions. Under phosphate-limited anaerobic conditions and with glycerol as the electron donor, non-growing Serratia cells could precipitate 0.5 mM of uranium supplied as soluble U(VI), via reduction to nano-crystalline U(IV) uraninite. Some evidence for the reduction of solid phase uranyl(VI) phosphate was also observed. This study highlights the potential for Serratia and related species to play a role in the bioremediation of uranium contamination, via a range of different metabolic pathways, dependent on culturing or in situ conditions. PMID- 26132211 TI - Colloidal Drop Deposition on Porous Substrates: Competition among Particle Motion, Evaporation, and Infiltration. AB - Recent interest in printable electronics and in particular paper- and textile based electronics has fueled research in inkjet printing of colloidal drops on porous substrates. On nonporous substrates, the interplay of particle motion and solvent evaporation determines the final deposition morphology of the evaporating colloidal drop. For porous substrates, solvent infiltration into the pores adds a layer of complexity to the deposition patterns that have not been fully elucidated in the literature. In this study, the deposition of picoliter-sized aqueous colloidal droplets containing nanometer- and micrometer-sized particles onto nanoporous anodic aluminum oxide substrates is examined for different drop and particle sizes and relative humidities as well as pore diameters, porosities, and wettabilities of the porous substrates. For the cases considered, solvent infiltration is found to be much faster than both evaporation and particle motion near the contact line, and thus when the substrate fully imbibes the solvent, the well-known "coffee-ring" deposition is suppressed. However, when the solvent is only partially imbibed, a residual droplet volume exists upon completion of the infiltration. For such cases, two time scales are of importance: the time for particle motion to the contact line as a result of both diffusion and advection, t(P), and the evaporation time of the residual drop volume, t(EI). Their ratio, t(P)/t(EI), determines whether the coffee-ring deposition will be formed (t(P)/t(EI) < 1) or suppressed (t(P)/t(EI) > 1). PMID- 26132212 TI - Examining Associations between Self-Rated Health and Proficiency in Literacy and Numeracy among Immigrants and U.S.-Born Adults: Evidence from the Program for the International Assessment of Adult Competencies (PIAAC). AB - This paper uses data from the Program for the International Assessment of Adult Competencies (PIAAC) to analyze the relationship between self-reported health (SRH) and literacy and numeracy proficiency for immigrants compared to U.S.-born respondents and for Hispanic versus Asian immigrants. The research questions were: (1) Are literacy and numeracy scores associated with adults' SRH? (2) Are associations between SRH and literacy and numeracy proficiency moderated by immigrant status? (3) Among immigrants, are literacy and numeracy scores more strongly associated with SRH for Hispanics versus Asians? Immigrants had significantly lower literacy and numeracy scores, yet reported better health than U.S.-born respondents. Ordinal logistic regression analyses showed that literacy and numeracy were both positively related to SRH for immigrants and U.S.-born adults, and should therefore be viewed as part of the growing evidence that literacy is an independent and significant social determinant of health. Second, U.S.-born and immigrant adults accrued similarly positive health benefits from stronger literacy and numeracy skills. Third, although Hispanic immigrants were more disadvantaged than Asian immigrants on almost all socioeconomic characteristics and had significantly lower literacy and numeracy scores and worse SRH than Asian immigrants, both Hispanic and Asian immigrants experienced similar positive health returns from literacy and numeracy proficiency. These findings underscore the potential health benefits of providing adult basic education instruction, particularly for immigrants with the least formal schooling and fewest socioeconomic resources. PMID- 26132213 TI - Trends and determinants of gastric bacterial colonization of preterm neonates in a NICU setting. AB - BACKGROUND: Newborn gastrointestinal (GI) tract is considered sterile but rapidly acquires a diverse microbiota from its intimate environment. Early acquisition of a bacterial species in the upper GI tract may play a role in establishing the colonic microbiota. There is paucity of molecular data on the upper GI tract microbiota in preterm neonates. METHODS: Gastric aspirates from 22 neonates with an average gestational age 27.7 weeks (+/-2.8), weighing 973.2 grams (+/-297.9) admitted to a neonatal intensive care unit were collected prospectively from weeks 1-4 of life. All samples were evaluated for microbiota using 16S rRNA-based Denaturing Gradient Gel Electrophoresis. Bacterial species colonization and its association with maternal and neonatal demographics, and neonatal clinical characteristics were analyzed. RESULTS: Bacteroides spp. was the predominant species in all four weeks. Bifidobacterium spp. colonization was significantly higher in exclusively breast milk fed compared to partially breast milk (PBM) fed neonates in first (p = 0.03) and third (p = 0.03) week of life. Anaerobic bacteria colonization decreased from first through fourth week of life (p = 0.03). Aerobic bacteria colonization was highly dynamic throughout the four week period. Premature rupture of membrane (p = 0.05) and birth outside of study hospital (p = 0.006) influenced the acquisition of bacteria in the first week of life. Birth weight was positively correlated with total number of bacterial species (p = 0.002) and anaerobes (p = 0.004) in PBM-fed neonates during the fourth week of life. H. pylori and Ureaplasma were not detected in any of our samples. CONCLUSION: Gastric bacterial colonization in preterm neonates is unstable during early weeks of life. Delayed oral feeding and use of antibiotics may be responsible for paucity of bacterial species. Monitoring of the gastric microbiota and concurrent examination of stool microbiota may yield important information on the utility of gastric signature patterns for predicting colon microbiota that may drive GI and immune dysfunctions. PMID- 26132214 TI - Structures of cGMP-Dependent Protein Kinase (PKG) Ialpha Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability. AB - cGMP-dependent protein kinase (PKG) Ialpha is a central regulator of smooth muscle tone and vasorelaxation. The N-terminal leucine zipper (LZ) domain dimerizes and targets PKG Ialpha by interacting with G-kinase-anchoring proteins. The PKG Ialpha LZ contains C42 that is known to form a disulfide bond upon oxidation and to activate PKG Ialpha. To understand the molecular details of the PKG Ialpha LZ and C42-C42' disulfide bond, we determined crystal structures of the PKG Ialpha wild-type (WT) LZ and C42L LZ. Our data demonstrate that the C42 C42' disulfide bond dramatically stabilizes PKG Ialpha and that the C42L mutant mimics the oxidized WT LZ structurally. PMID- 26132215 TI - Properties of targeted preamplification in DNA and cDNA quantification. AB - OBJECTIVE: Quantification of small molecule numbers often requires preamplification to generate enough copies for accurate downstream enumerations. Here, we studied experimental parameters in targeted preamplification and their effects on downstream quantitative real-time PCR (qPCR). METHODS: To evaluate different strategies, we monitored the preamplification reaction in real-time using SYBR Green detection chemistry followed by melting curve analysis. Furthermore, individual targets were evaluated by qPCR. RESULT: The preamplification reaction performed best when a large number of primer pairs was included in the primer pool. In addition, preamplification efficiency, reproducibility and specificity were found to depend on the number of template molecules present, primer concentration, annealing time and annealing temperature. The amount of nonspecific PCR products could also be reduced about 1000-fold using bovine serum albumin, glycerol and formamide in the preamplification. CONCLUSION: On the basis of our findings, we provide recommendations how to perform robust and highly accurate targeted preamplification in combination with qPCR or next-generation sequencing. PMID- 26132217 TI - Laser-Modified Black Titanium Oxide Nanospheres and Their Photocatalytic Activities under Visible Light. AB - A facile pulse laser ablation approach for preparing black titanium oxide nanospheres, which could be used as photocatalysts under visible light, is proposed. The black titanium oxide nanospheres are prepared by pulsed-laser irradiation of pure titanium oxide in suspended aqueous solution. The crystalline phases, morphology, and optical properties of the obtained nanospheres are characterized by means of X-ray diffraction (XRD), field-emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS), and UV-vis NIR diffuse reflectance spectroscopy. It is shown that high-energy laser ablation of titanium oxide suspended solution benefited the formation of Ti(3+) species and surface disorder on the surface of the titanium oxide nanospheres. The laser modified black titanium oxide nanospheres could absorb the full spectrum of visible light, thus exhibiting good photocatalytic performance under visible light. PMID- 26132216 TI - Modeling of Virion Collisions in Cervicovaginal Mucus Reveals Limits on Agglutination as the Protective Mechanism of Secretory Immunoglobulin A. AB - Secretory immunoglobulin A (sIgA), a dimeric antibody found in high quantities in the gastrointestinal mucosa, is broadly associated with mucosal immune protection. A distinguishing feature of sIgA is its ability to crosslink pathogens, thereby creating pathogen/sIgA aggregates that are too large to traverse the dense matrix of mucin fibers in mucus layers overlying epithelial cells and consequently reducing infectivity. Here, we use modeling to investigate this mechanism of "immune exclusion" based on sIgA-mediated agglutination, in particular the potential use of sIgA to agglutinate HIV in cervicovaginal mucus (CVM) and prevent HIV transmission. Utilizing reported data on HIV diffusion in CVM and semen, we simulate HIV collision kinetics in physiologically-thick mucus layers-a necessary first step for sIgA-induced aggregation. We find that even at the median HIV load in semen of acutely infected individuals possessing high viral titers, over 99% of HIV virions will penetrate CVM and reach the vaginal epithelium without colliding with another virion. These findings imply that agglutination is unlikely to be the dominant mechanism of sIgA-mediated protection against HIV or other sexually transmitted pathogens. Rather, we surmise that agglutination is most effective against pathogens either present at exceedingly high concentrations or that possess motility mechanisms other than Brownian diffusion that significantly enhance encounter rates. PMID- 26132218 TI - Eating Disorder in Juvenile Fibromyalgia. PMID- 26132219 TI - Adapting a Driving Simulator to Study Pedestrians' Street-Crossing Decisions: A Feasibility Study. AB - The decision when to cross a street safely is a challenging task that poses high demands on perception and cognition. Both can be affected by normal aging, neurodegenerative disorder, and brain injury, and there is an increasing interest in studying street-crossing decisions. In this article, we describe how driving simulators can be modified to study pedestrians' street-crossing decisions. The driving simulator's projection system and the virtual driving environment were used to present street-crossing scenarios to the participants. New sensors were added to measure when the test person starts to cross the street. Outcome measures were feasibility, usability, task performance, and visual exploration behavior, and were measured in 15 younger persons, 15 older persons, and 5 post stroke patients. The experiments showed that the test is feasible and usable, and the selected difficulty level was appropriate. Significant differences in the number of crashes between young participants and patients (p = .001) as well as between healthy older participants and patients (p = .003) were found. When the approaching vehicle's speed is high, significant differences between younger and older participants were found as well (p = .038). Overall, the new test setup was well accepted, and we demonstrated that driving simulators can be used to study pedestrians' street-crossing decisions. PMID- 26132220 TI - The Effect of a Liner on the Dispersion of Sacral Interface Pressures During Spinal Immobilization. AB - Sacral pressure ulcers are a significant problem following spinal cord injury and are felt to be in part due to the high interface-pressures generated while strapped to the spine board. The objective of this study was to determine sacral interface-pressure and sensing area in healthy volunteers on a spine board and the effects of a gel pressure dispersion liner. Thirty-seven volunteers were placed on a pressure-sensing mat between the subject and the spine board. Measurements were carried out with and without a gel liner. Pressures and sensing area were recorded every minute for 40 minutes. The highest pressure was generated at the sacral prominence of each subject. Mean interface-pressures were higher on the spine board alone than with the gel liner (p < .0001). Overall, mean sensing area was lower on the spine board than with the gel liner (p < .0001). Standard spinal immobilization causes high sacral interface-pressures. The addition of a gel liner on the spine board decreased overall mean sacral pressures and increased mean sensing area. Generation of sacral pressure ulcers may be related to the initial interface-pressures generated while the patient is strapped to the spine board. The addition of a gel liner may reduce the incidence of sacral pressure ulcers. PMID- 26132221 TI - Validity of a Smartphone-Based Fall Detection Application on Different Phones Worn on a Belt or in a Trouser Pocket. AB - The objective of this study was to evaluate the sensitivity and specificity of a smartphone-based fall detection application when different smartphone models are worn on a belt or in a trouser pocket. Eight healthy adults aged between 18 and 24 years old simulated 10 different types of true falls, 5 different types of falls with recovery, and 11 daily activities, five consecutive times. Participants wore one smartphone in a pocket that was attached to their belt and another one in their trouser pocket. All smartphones were equipped with a built in accelerometer and the fall detection application. Four participants tested the application on a Samsung S3 and four tested the application on a Samsung S3 mini. Sensitivity scores were .75 (Samsung S3 belt), .88 (Samsung S3 mini trouser pocket), and .90 (Samsung S3 mini belt/Samsung S3 trouser pocket). Specificity scores were .87 (Samsung S3 trouser pocket), .91 (Samsung S3 mini trouser pocket), .97 (Samsung S3 belt), and .99 (Samsung S3 mini belt). These results suggest that an application on a smartphone can generate valid fall alarms when worn on a belt or in a trouser pocket. However, sensitivity should be improved before implementation of the application in practice. PMID- 26132222 TI - Socket Interface Pressure and Amputee Reported Outcomes for Comfortable and Uncomfortable Conditions of Patellar Tendon Bearing Socket: A Pilot Study. AB - The objectives of the current study were to compare intra-socket pressure differences between comfortable and uncomfortable socket conditions, and the usefulness of subject perception of satisfaction, activity limitations, and socket comfort in distinguishing between these two socket conditions. Five unilateral trans-tibial amputees took part in the study. They answered the Socket Comfort Score (SCS) and Trinity Amputation and Prosthetic Experience Scale (TAPES) questionnaires before the interface pressure (in standing and walking) was measured for the uncomfortable socket condition at five regions of the residual limb. Participants were then provided with a comfortable socket and wore it for two weeks. Participants who were satisfied with the socket fit after two weeks repeated the SCS and TAPES questionnaires and interface pressure measurements. The differences between the test results of the two conditions were not statistically significant, except for the interface pressure at the popliteal region during the early stance phase, TAPES socket fit subscale, and the SCS. Due to large variability of the data and the lack of statistical significance, no firm conclusion can be made on the possible relationship between the interface pressure values and the patient-reported outcomes of the two socket conditions. A larger sample size and longer acclimation period are required to locate significant differences. PMID- 26132224 TI - A Kinect-Based Sign Language Hand Gesture Recognition System for Hearing- and Speech-Impaired: A Pilot Study of Pakistani Sign Language. AB - Sign language provides hearing and speech impaired individuals with an interface to communicate with other members of the society. Unfortunately, sign language is not understood by most of the common people. For this, a gadget based on image processing and pattern recognition can provide with a vital aid for detecting and translating sign language into a vocal language. This work presents a system for detecting and understanding the sign language gestures by a custom built software tool and later translating the gesture into a vocal language. For the purpose of recognizing a particular gesture, the system employs a Dynamic Time Warping (DTW) algorithm and an off-the-shelf software tool is employed for vocal language generation. Microsoft((r)) Kinect is the primary tool used to capture video stream of a user. The proposed method is capable of successfully detecting gestures stored in the dictionary with an accuracy of 91%. The proposed system has the ability to define and add custom made gestures. Based on an experiment in which 10 individuals with impairments used the system to communicate with 5 people with no disability, 87% agreed that the system was useful. PMID- 26132225 TI - Providing Assistive Technology Applications as a Service Through Cloud Computing. AB - Users with disabilities interact with Personal Computers (PCs) using Assistive Technology (AT) software solutions. Such applications run on a PC that a person with a disability commonly uses. However the configuration of AT applications is not trivial at all, especially whenever the user needs to work on a PC that does not allow him/her to rely on his / her AT tools (e.g., at work, at university, in an Internet point). In this paper, we discuss how cloud computing provides a valid technological solution to enhance such a scenario.With the emergence of cloud computing, many applications are executed on top of virtual machines (VMs). Virtualization allows us to achieve a software implementation of a real computer able to execute a standard operating system and any kind of application. In this paper we propose to build personalized VMs running AT programs and settings. By using the remote desktop technology, our solution enables users to control their customized virtual desktop environment by means of an HTML5-based web interface running on any computer equipped with a browser, whenever they are. PMID- 26132226 TI - Improving Target Acquisition for Computer Users With Athetosis. AB - Prior work has highlighted the challenges faced by people with athetosis when trying to acquire on-screen targets using a mouse or trackball. The difficulty of positioning the mouse cursor within a confined area has been identified as a challenging task. We have developed a target acquisition assistance algorithm that features transition assistance via directional gain variation based on target prediction, settling assistance via gain reduction in the vicinity of a predicted target, and expansion of the predicted target as the cursor approaches it. We evaluated the algorithm on improving target acquisition efficiency among seven participants with athetoid cerebral palsy. Our results showed that the algorithm significantly reduced the overall movement time by about 20%. Considering the target acquisition occurs countless times in the course of regular computer use, the accumulative effect of such improvements can be significant for improving the efficiency of computer interaction among people with athetosis. PMID- 26132227 TI - Differences between Cryptococcus neoformans and Cryptococcus gattii in the Molecular Mechanisms Governing Utilization of D-Amino Acids as the Sole Nitrogen Source. AB - The ability to grow on media containing certain D-amino acids as a sole nitrogen source is widely utilized to differentiate Cryptococcus gattii from C. neoformans. We used the C. neoformans H99 and C. gattii R265 strains to dissect the mechanisms of D-amino acids utilization. We identified three putative D-amino acid oxidase (DAO) genes in both strains and showed that each DAO gene plays different roles in D-amino acid utilization in each strain. Deletion of DAO2 retarded growth of R265 on eleven D-amino acids suggesting its prominent role on D-amino acid assimilation in R265. All three R265 DAO genes contributed to growth on D-Asn and D-Asp. DAO3 was required for growth and detoxification of D-Glu by both R265 and H99. Although growth of H99 on most D-amino acids was poor, deletion of DAO1 or DAO3 further exacerbated it on four D-amino acids. Overexpression of DAO2 or DAO3 enabled H99 to grow robustly on several D-amino acids suggesting that expression levels of the native DAO genes in H99 were insufficient for growth on D-amino acids. Replacing the H99 DAO2 gene with a single copy of the R265 DAO2 gene also enabled its utilization of several D-amino acids. Results of gene and promoter swaps of the DAO2 genes suggested that enzymatic activity of Dao2 in H99 might be lower compared to the R265 strain. A reduction in virulence was only observed when all DAO genes were deleted in R265 but not in H99 indicating a pathobiologically exclusive role of the DAO genes in R265. These results suggest that C. neoformans and C. gattii divergently evolved in D-amino acid utilization influenced by their major ecological niches. PMID- 26132228 TI - Predictors of Health Care Use of Women with Breast Cancer: A Systematic Review. AB - The aim of this study was to identify predictors of health care use among women with breast cancer by conducting a systematic review. Potentially relevant studies were identified by searching the PubMed, EMBASE, PsycINFO, CINAHL, and Cochrane Library databases. Also, backward and forward citation searches were performed. Studies were selected if they addressed associations between (a) sociodemographic, enabling (e.g., income), clinical and health related, or psychosocial predictors, and (b) medical, psychosocial, or paramedical health care use of adult women with breast cancer. The health care types of interest were hospital utilization and provider visits. An evaluation of aggregated findings was performed to determine consistency of findings between studies. Sixteen studies were included in the review. Higher age, a more advanced cancer stage, more comorbid disorders, having a mastectomy, a lymph node dissection, and breast reconstruction were consistently associated with higher hospital utilization. None of the patient characteristics were consistently associated with medical, psychosocial, or paramedical health care use-but psychosocial or paramedical associations were also less examined. In conclusion, sociodemographic, medical, and treatment-related factors were consistently associated with (higher) health care use of breast cancer patients. Practitioners may use this information to anticipate future use of subgroups of patients. Results may also be used in the development of interventions that target relevant predictors, to reduce patients' health care use and accompanying health care costs. Furthermore, more research is needed to identify predictors of psychosocial and paramedical health care use. PMID- 26132229 TI - Reporting quality of randomised controlled trials published in prosthodontic and implantology journals. AB - The purpose of this study was to examine the reporting quality of randomised controlled trials (RCTs) published in prosthodontic and implantology journals. Thirty issues of nine journals in prosthodontics and implant dentistry were searched for RCTs, covering the years 2005-2012: The Journal of Prosthetic Dentistry, Journal of Oral Rehabilitation, The International Journal of Prosthodontics, The International Journal of Periodontics & Restorative Dentistry, Clinical Oral Implants Research, Clinical Implant Dentistry & Related Research, The International Journal of Oral & Maxillofacial Implants, Implant Dentistry and Journal of Dentistry. The reporting quality was assessed using a modified Consolidated Standards of Reporting Trials (CONSORT) statement checklist. Data were analysed using descriptive statistics followed by univariable and multivariable examination of statistical associations (alpha = 0.05). A total of 147 RCTs were identified with a mean CONSORT score of 69.4 (s.d. = 9.7). Significant differences were found among journals with the Journal of Oral Rehabilitation achieving the highest score (80.6, s.d. = 5.5) followed by Clinical Oral Implants Research (73.7, s.d. = 8.3). Involvement of a statistician/methodologist was significantly associated with increased CONSORT scores. Overall, the reporting quality of RCTs in major prosthodontic and implantology journals requires improvement. This is of paramount importance considering that optimal reporting of RCTs is an important prerequisite for clinical decision-making. PMID- 26132230 TI - Reversible Oxidation of a Conserved Methionine in the Nuclear Export Sequence Determines Subcellular Distribution and Activity of the Fungal Nitrate Regulator NirA. AB - The assimilation of nitrate, a most important soil nitrogen source, is tightly regulated in microorganisms and plants. In Aspergillus nidulans, during the transcriptional activation process of nitrate assimilatory genes, the interaction between the pathway-specific transcription factor NirA and the exportin KapK/CRM1 is disrupted, and this leads to rapid nuclear accumulation and transcriptional activity of NirA. In this work by mass spectrometry, we found that in the absence of nitrate, when NirA is inactive and predominantly cytosolic, methionine 169 in the nuclear export sequence (NES) is oxidized to methionine sulfoxide (Metox169). This oxidation depends on FmoB, a flavin-containing monooxygenase which in vitro uses methionine and cysteine, but not glutathione, as oxidation substrates. The function of FmoB cannot be replaced by alternative Fmo proteins present in A. nidulans. Exposure of A. nidulans cells to nitrate led to rapid reduction of NirA Metox169 to Met169; this reduction being independent from thioredoxin and classical methionine sulfoxide reductases. Replacement of Met169 by isoleucine, a sterically similar but not oxidizable residue, led to partial loss of NirA activity and insensitivity to FmoB-mediated nuclear export. In contrast, replacement of Met169 by alanine transformed the protein into a permanently nuclear and active transcription factor. Co-immunoprecipitation analysis of NirA KapK interactions and subcellular localization studies of NirA mutants lacking different parts of the protein provided evidence that Met169 oxidation leads to a change in NirA conformation. Based on these results we propose that in the presence of nitrate the activation domain is exposed, but the NES is masked by a central portion of the protein (termed nitrate responsive domain, NiRD), thus restricting active NirA molecules to the nucleus. In the absence of nitrate, Met169 in the NES is oxidized by an FmoB-dependent process leading to loss of protection by the NiRD, NES exposure, and relocation of the inactive NirA to the cytosol. PMID- 26132231 TI - Multi-Biomarkers for Early Detection of Type 2 Diabetes, Including 10- and 12 (Z,E)-Hydroxyoctadecadienoic Acids, Insulin, Leptin, and Adiponectin. AB - We have previously found that fasting plasma levels of totally assessed 10- and 12-(Z,E)-hydroxyoctadecadienoic acid (HODE) correlated well with levels of glycated hemoglobin (HbA1c) and glucose during oral glucose tolerance tests (OGTT); these levels were determined via liquid chromatography-mass spectrometry after reduction and saponification. However, 10- and 12-(Z,E)-HODE alone cannot perfectly detect early impaired glucose tolerance (IGT) and/or insulin resistance, which ultimately lead to diabetes. In this study, we randomly recruited healthy volunteers (n = 57) who had no known history of any diseases, and who were evaluated using the OGTT, the HODE biomarkers, and several additional proposed biomarkers, including retinol binding protein 4 (RBP4), adiponectin, leptin, insulin, glycoalbumin, and high sensitivity-C-reactive protein. The OGTT revealed that our volunteers included normal individuals (n = 44; Group N), "high-normal" individuals (fasting plasma glucose 100-109 mg/dL) with IGT (n = 11; Group HN+IGT), and diabetic individuals (n = 2; Group D). We then used these groups to evaluate the potential biomarkers for the early detection of type 2 diabetes. Plasma levels of RBP4 and glycoalbumin were higher in Group HN+IGT, compared to those in Group N, and fasting levels of 10- and 12 (Z,E)-HODE/linoleic acids were significantly correlated with levels of RBP4 (p = 0.003, r = 0.380) and glycoalbumin (p = 0.006, r = 0.316). Furthermore, we developed a stepwise multiple linear regression models to predict the individuals' insulin resistance index (the Matsuda Index 3). Fasting plasma levels of 10- and 12-(Z,E)-HODE/linoleic acids, glucose, insulin, and leptin/adiponectin were selected as the explanatory variables for the models. The risks of type 2 diabetes, early IGT, and insulin resistance were perfectly predicted by comparing fasting glucose levels to the estimated Matsuda Index 3 (fasting levels of 10- and 12-(Z,E)-HODE/linoleic acids, insulin, and leptin/adiponectin). PMID- 26132232 TI - Screening Foodstuffs for Class 1 Integrons and Gene Cassettes. AB - Antibiotic resistance is one of the greatest threats to health in the 21st century. Acquisition of resistance genes via lateral gene transfer is a major factor in the spread of diverse resistance mechanisms. Amongst the DNA elements facilitating lateral transfer, the class 1 integrons have largely been responsible for spreading antibiotic resistance determinants amongst Gram negative pathogens. In total, these integrons have acquired and disseminated over 130 different antibiotic resistance genes. With continued antibiotic use, class 1 integrons have become ubiquitous in commensals and pathogens of humans and their domesticated animals. As a consequence, they can now be found in all human waste streams, where they continue to acquire new genes, and have the potential to cycle back into humans via the food chain. This protocol details a streamlined approach for detecting class 1 integrons and their associated resistance gene cassettes in foodstuffs, using culturing and PCR. Using this protocol, researchers should be able to: collect and prepare samples to make enriched cultures and screen for class 1 integrons; isolate single bacterial colonies to identify integron-positive isolates; identify bacterial species that contain class 1 integrons; and characterize these integrons and their associated gene cassettes. PMID- 26132235 TI - The importance of scientific publication in the development of public health. PMID- 26132234 TI - Association between Visit-to-Visit Glucose Variability and Cognitive Function in Aged Type 2 Diabetic Patients: A Cross-Sectional Study. AB - BACKGROUND AND PURPOSE: Diabetes is associated with cognitive decline as well as the development of dementia. Although mean blood glucose levels are typically used to assess the status of diabetic patients, glucose variability is also involved in the manifestation of macro- and microvascular complications in this population. Thus, the present study sought to determine whether visit-to-visit glucose variability contributes to cognitive decline in patients with type 2 diabetes. METHODS: The present study assessed 68 patients with type 2 diabetes using several validated neuropsychological measures. All patients had no cerebrovascular disease, history of hypoglycemia, psychiatric conditions, or other medical illnesses. Standard deviations (SDs) and coefficients of variance (CVs) of the patients' blood glucose (after fasting and 2 hours postprandial; FBS and PP2), and glycated hemoglobin (HbA1c) values were used as indices of glucose variability. The cognitive outcome parameters were transformed with z-scores and entered into a multiple linear regression model that included educational status, age, sex, vascular risk factors, and mean glucose parameters as covariates. RESULTS: The mean age of the total patient population was 70.9 years; 46 (67.6%) of the patients were men, and the median follow-up duration at our endocrinology outpatient clinic was 4.8 years. The mean FBS and PP2 glucose levels of the patients were 132 mg/dL and 199 mg/dL, respectively, and the mean HbA1c level was 8.0%. A univariable analysis revealed that only the PP2 value was associated with the Mini-Mental State Examination (MMSE) score, and multivariable analysis revealed that a high SD and/or CV for PP2 glucose were associated with low scores on the Rey Complex Figure Copy test and/or the Verbal Learning Test. Additionally, a high SD and a higher CV for HbA1c level were significantly associated with low MMSE and Digit Span test scores even after adjusting for mean HbA1c values. CONCLUSIONS: The present data indicate that a greater degree of visit-to-visit glucose variability influenced specific types of cognitive function in type 2 diabetic patients independently of mean blood glucose levels. Future studies should focus on whether reductions in glycemic variability will improve the cognitive decline observed in type 2 diabetic patients. PMID- 26132236 TI - The Ciencia & Saude Coletiva journal and the process of institutionalization of a field of knowledge and practices. AB - This paper takes as its starting point the concepts that make up the process of institutionalization of a field of knowledge in the following phases: 1. Differentiation of subjects, methods and techniques of knowledge or existing disciplines, 2. The subject previously considered as peripheral is now seem as part of a particular field of knowledge, 3. The new field becomes significant in the set of an area and starts the standardization of recruitment of human resources, selection of experts and financial resources, and 4. Consolidation of the new field, building its culture within the scientific community, with its social networks of communication, scientific associations and its own publications. Our central objective is to analyze the role of the Ciencia e Saude Coletiva Journal in the process of institutionalization of the Collective Health; we situate the Collective Health and its stages, make a brief report on the history of scientific publications by emphasizing the Brazilian studies on the public health field, and work the early stages of the Journal. PMID- 26132237 TI - Indicators of national focus of the research published by Public Health journals edited in Brazil. AB - This report presents a set of bibliometric indicators and statistics which explain the high level of production of articles on research in public and collective health in Brazil which are published in the main nationally edited journals in the field. The predominance of publications in the Portuguese language by Brazilian authors results in a lower impact in terms of citations received as measured by the bibliometric indexes Scimago/Scopus and JCR/WoS. These bibliometric indexes are used to measure the production and performance of research and journals. Nevertheless, the performance of these same journals stands out in SciELO, and is competitive internationally in the broader context of Google Scholar Metrics. The challenge faced by journals in Brazil is developing and applying editorial policies for the valuation of research with a national focus, and its internationalization. PMID- 26132238 TI - Editorial challenges of the Revista de Saude Publica. AB - The editors of the Revista de Saude Publica describe the journal's editorial profile and discuss the challenges of scientific publication in the area. A historical overview of almost 50 years of the journal is reported, with the temporal projection of their bibliometric indicators. Qualitative and quantitative parameters of its editorial profile and indexes are also reported. Budget constraints and the actions being taken to address them are discussed. The difficulty in allocating reviewers for manuscripts submitted to the editorial process is also discussed; an issue that affects scientific publication in many areas of knowledge. In particular, we sought to reflect on the proposal of measures to boost the editorial process by alleviating the shortage of reviewers and their possible harmful consequences for the editorial process. PMID- 26132239 TI - A brief history of cadernos de Saude Publica/reports in Public Health. AB - This article was written as part of the 20th-year commemorative issue of Ciencia e Saude Coletiva (C&SC). We take advantage of this opportunity to revisit the successful history of Cadernos de Saude Publica (CSP)/Reports in Public Health in its 30 years of publication, progressing from a quarterly periodical with limited circulation to a monthly journal indexed in the main scientific databases. We also summarize some themes from our recent editorials, including the internationalization of scientific journals, the demand for relevant and original articles, plagiarism, and peer review. We also discuss the article submission management system developed by CSP and conclude with ideas on cooperation between journals in the public health field. PMID- 26132240 TI - Ciencia & Saude coletiva Journal at the national and international context of scientific communication. AB - The article discusses the role of the Ciencia & Saude Coletiva Journal in the dissemination of knowledge in Brazil and in the international scientific community, its new challenges and role in the consolidation of the national public health field. Its history is outlined, positioning it as a scientific journal and the themes approached in it are analyzed. Among the findings, it is emphasized that the journal features a structured space by the habitus of public health, and creates its own habitus that contributes to structure this field. In addition, the journal contributes to the development of critical mass in the area and is committed to the Brazilian Public Health System. PMID- 26132241 TI - The history of a movement: Saude em Debate magazine and Brazilian health reform. AB - This article traces significant moments in the history of the magazine Saude em Debate - sourcing references and information from documents, historical studies, editions of the magazine, academic work and interviews with physicians and writers who contributed to its creation. In its 39 years of existence, although there may have been variations in the magazine's editorial policy, its role as a means for exchange of ideas and debate on critical health thinking, and making a contribution by in some way intervening in the Brazilian political process, has not changed. The magazine established itself with a firm reputation as a vehicle of scientific communication especially in the areas of health policy and management, expanding the scope of subjects over time. Among the challenges it has faced, as well as that of financial sustenance, has been its role as an instrument for dissemination of Latin American thinking in the field of health. PMID- 26132242 TI - The Brazilian Journal of Epidemiology: 18 years of contributing to knowledge dissemination. AB - The Revista Brasileira de Epidemiologia (RBE - Brazilian Journal of Epidemiology) is completing 18 years as a vehicle for the dissemination of knowledge in the area of health. This knowledge relates to theoretical perspectives, the analysis of the reality of existing health conditions, as well as practices within health services. Fitting within all the disciplines of the field of public health, the origins of this journal, and the concepts that it covers, reflect movements within the health sector and also shadow the areas of operation proposed in the "Master Plans for the Development of Epidemiology in Brazil". Over time, there has been increasing demand for the publication of articles within the journal, a fact that has favored its growing impact factor. The RBE adopted an editorial policy designed to disseminate its production in a bilingual form in order to attain greater international visibility and to meet the needs of both researchers and professionals in the field. Like all Brazilian scientific journals, it has suffered from the absence of national scien-tific and technological policies designed to provide more effective assistive in ensuring its sustainability. Looking towards the future, it is hoped that the RBE will achieve even greater impact within academia, in relation to health service professionals, and, not least, that it will achieve a high impact within society at large. PMID- 26132243 TI - From occupational safety and health to Workers' Health: history and challenges to the Brazilian Journal of Occupational Health. AB - The Revista Brasileira de Saude Ocupacional (RBSO) - Brazilian Journal of Occupational Health - is an academic peer-reviewed journal in the field of Workers' Health that has been published by Fundacentro since 1973. Its historical trajectory, current performance, challenges and future perspectives were approached, in this paper, from a documental analysis. The journal's history can be divided into three periods, starting during the military government. At the beginning, the journal was the official vehicle for the Brazilian occupational accidents prevention policy, in which Fundacentro played a central role. The early 1980s opens space for technical-scientific publications and the field of Workers' Health emerges on the journal's pages. In 2005-6, a restructuring process is implemented, ensuring independent editorial policy and structures. Since 2006, 139 original papers and 9 thematic issues have been published. The journal is indexed in 9 bibliographic databases, has been ranked B1 in the field of interdisciplinary studies and B2 in the field of public health by CAPES, has an upward trend in the SciELO Impact Factor, and has an h-index of 5 in Google Scholar. Nevertheless, the low scientific production in the field and the high rate of rejection of manuscripts may jeopardize the survival of the journal, which is the main locus for scientific publications in the field of Workers' Health. PMID- 26132244 TI - Celebrating Ciencia & Saude Coletiva, reminiscing about the trajectory of Physis. AB - We describe the history and characteristics of the journal Physis by presenting an overview of what was published in the 24 years since its first issue. We present some data relating to quotations and a critical discussion of same. We end with a discussion of recently observed movements in policies of government agencies regarding scientific policy, expressing our concern and advocating a policy fomenting the diversity and the broadening of the scope of vehicles of scientific dissemination. PMID- 26132245 TI - An interdisciplinary space of scientific communication in Collective (Public) Health: the journal interface--Communication, Health, Education. AB - This is a reflection upon 17 years of experience in the production of an interdisciplinary scientific journal, the publication "Interface: Communication, Health, Education," whose scope is in the fields of Collective (Public) Health, Education and Communication. It also examines retrospectively the themes published by the journal, seeking to identify them in different sections of this publication. Finally, the evolution of the journal is analyzed. PMID- 26132246 TI - Saude e Sociedade Journal: partnership and openness to new approaches. AB - The text traces the trajectory of the Saude e Sociedade scientific journal, published by the School of Public Health, University of Sao Paulo in partnership with the Associacao Paulista de Saude Publica since 1992. It presents the context of the era in which the journal was created and its mission of divulging the contributions of Human and Social Sciences to Health Care, the challenges it has faced over the length of its history until today, its goals and strategies for improving scientific quality, the journal's visibility, becoming indexed in various national and international bibliographic databases and about its internationalization and sustainability, reaffirming its founding principles. PMID- 26132247 TI - Epidemiology and Health Services: the trajectory of the Brazilian National Health System Journal. AB - Epidemiology and Health Services - Brazilian National Health System Journal (Epidemiologia e Servicos de Saude - RESS) is a scientific journal published by the Brazilian Ministry of Health. It is the continuation of the Brazilian National Health System Epidemiological Report (Informe Epidemiologico do SUS - IESUS), created in 1992. Its name changed to Epidemiology and Health Services in 2003. RESS is centred on epidemiology in health services. Its mission is to disseminate epidemiological knowledge applicable to the surveillance, prevention and control of diseases relevant to Public Health, aiming to improve the services offered by the Brazilian National Health System. This article describes RESS' trajectory, right from its creation as IESUS, up until its consolidation as an important Brazilian scientific journal in the Public Health field. Initiatives that have contributed to the journal's development are highlighted, such as the revision and implementation of the plan to strengthen the journal, the growth of its editorial board, actions aimed at promoting publication integrity, as well as activities to disseminate it, including the creation of the RESS Evidencia Prize. As a result, RESS has evolved greatly in terms of its performance indicators and was indexed in relevant bibliographical databases. PMID- 26132248 TI - Body dissatisfaction among pregnant women: an integrative review of the literature. AB - The body image of pregnant women is an issue that should be further investigated by professionals in the area, especially in view of the fact that maternal and infant health has gained such prominence. The scope of this integrative review is to analyze the literature relating to body image and body dissatisfaction among pregnant women. Research was based on articles extracted from the Scopus, PubMed, BVS and PsycINFO databases, by cross-referencing "pregnancy" with the keywords "body image" and "body dissatisfaction." Once the inclusion and exclusion criteria had been adopted, forty studies were analyzed. These produced inconclusive data about body dissatisfaction during pregnancy. Symptoms of depression, low self-esteem, an inadequate approach towards healthy eating and weight gain above recommended limits have been associated with a negative body image. The contradictory findings could be related to the different instruments used to measure body image. In view of the possible impact that a negative body image can have on maternal and infant health during pregnancy, it is recommended that further investigations are made, in particular related to the development of a specific tool to evaluate the body image of pregnant women. PMID- 26132249 TI - Vulnerability synthetic indices: a literature integrative review. AB - The concept of vulnerability is delimited by dynamic social and multigenerational processes involving at least three dimensions: exposure to risk trajectories, internal and external capabilities of reaction and possibilities of adaptation based on both the intensity of risk and the resilience of people. In order to identify and describe the synthetic indices of vulnerability, there was an integrative literature review. We consulted free access articles indexed in the following databases: BioMed, Bireme, PubMed, Reldalyc, SciELO and Web of Science; and we used controlled descriptors in English and Portuguese for all time slots available with selection and analysis of 47 studies that reported results of 23 synthetic indices of vulnerability. The results showed that the synthetic indices of vulnerability address four themes: social determinants of health; environmental and climatic conditions; family and course of life; territories and specific geographic areas. It was concluded that the definition of the components and indicators, as well as the methodologies adopted for the construction of synthetic indices need to be evaluated by means of the limitations and advantages of reporting the vulnerability through summary measures in policy formulation and decision-making aimed at human development. PMID- 26132250 TI - [Boletim Epidemiologico Paulista (Paulista Epidemiologic Bulletin)--persistent trajectory]. AB - The Paulista Epidemiologic Bulletin (Bepa), created in 2004 is a monthly publication from the Coordinating Office of Diseases Control (CCD), from the State Office of Health of Sao Paulo (SES-SP) responsible for planning and executing actions of health promotion and preventing any risks and diseases throughout the covered areas of the system (SUS-SP). Originally as a proposal of a fast publication of objective informations it suffered transformations along the years and turned out to be an important tool for service actions and health managers. Funded exclusively by public resources it tries hard to maintain the monthly periodicity and disclosure of epidemiologic data, description of programmatic actions, health situation analysis and striking reports concerning the history of public health in Sao Paulo. PMID- 26132251 TI - Ilza Veith (1912-2013) and Genevieve Miller (1914-2013): long lives dedicated to the history of medicine. AB - This article analyzes bibliographic aspects of two historians of medicine: Ilza Veith (1912-2013) and Genevieve Miller (1914-2013). Both women trained at the Institute of History of Medicine at Johns Hopkins University and both had the historian Henry Ernest Sigerist (1891-1957) as their intellectual mentor. Both women were the authors of original works, Ilza in the field of oriental medicine and Genevieve in the field of the history of science, and throughout their careers they made important contributions to research, teaching and the dissemination of the history of medicine, which was marked by their pioneering activities. PMID- 26132253 TI - [Health at the border: quantitative and qualitative analysis of patients treated at the Maternal and Child Care Center in Foz do Iguacu, Brazil]. AB - Foz do Iguacu participates in the SIS-Fronteiras program and installed the Maternal and Child Care Center (CMI) to offer prenatal care service to pregnant Brazilian women resident in Paraguay (Brasiguaias). To analyze the characteristics of the CMI and compare the profile of Brasiguaias with pregnant Brazilian women resident in Brazil, a quantitative and qualitative approach in methodology was applied. It was found that Brasiguaias go to the CMI because of the precariousness of services of the Paraguayan Health System. They tend to be younger, bear more children, have lower education and are unmarried compared with pregnant Brazilian woman resident in Brazil. They omit where they live to avoid being denied the right or receiving inferior treatment than local pregnant Brazilian women and seek obstetric treatment later to avoid being denied attendance. Pregnant Brazilian women resident in Paraguay are onerous to the municipality, especially due to misinformation about their reproductive and pregnancy history, which increases the chances of undergoing cesarean delivery and hospitalization of the mother and/or infant due to complications. Effective actions in relation to maternal and child health in the border areas need to be prioritized. PMID- 26132252 TI - Guilherme Rodrigues da Silva: the development of the field of collective health in Brazil. AB - This article describes the academic trajectory of Professor Guilherme Rodrigues da Silva and his contribution in the formation of Collective Health in Brazil. Three key aspects are covered: active participation in medical education, both undergraduate and graduate level; its application in scientific research for the study of neglected diseases and the development of epidemiological methodology; his contribution in establishing health policy with emphasis on the Unique Health System (Sistema Unico de Saude - SUS). PMID- 26132254 TI - Qualitative study on adolescents' reasons to non-adherence to dental treatment. AB - The study aimed to reflect on adolescents' speeches regarding their justifications for non-adherence to dental treatment. This is a qualitative research derived from a quantitative research aimed at adolescents from 15 to 19 years of public schools belonging to the area of 34 Primary Health Units - Family Health, in Piracicaba, SP, in 2012. The adolescents were evaluated, diagnosed and referred for dental treatment. One year after this intervention and with non adherence to treatment, we used a qualitative method to deeply understand this phenomenon. We conducted 25 interviews with a semi-structured script, divided into three blocks: adopted or did not adopt actions recommended; arguments justifying the non-adherence of recommended actions; dimensions related to oral health importance. We adopted the thematic analysis and non-adherence was related to some aspects and grouped in: no priority; priority and change of priority. We concluded that the main reasons for non-adherence are related to different priorities, and orthodontic brace was a potent stimulator of interest and establishment of priorities in oral health care among adolescents. PMID- 26132255 TI - [Stressor events in the family environment that are indicative of mental health problems in children of school age]. AB - The scope of this article is to evaluate the relationship between stressor events that occurred last year in the family of children and adolescents that are indicative of mental health problems in a sample of students from two schools in a city in southern Brazil. It involved a cross-sectional study with 1,075 students enrolled in two public elementary schools. The Strengths and Difficulties Questionnaire was used to assess emotional and behavioral factors of the child and the Social Readjustment Rating Scale (SRRS) of Holmes and Rahe (1967) to assess stressor events. The chi-square and Poisson regression test with robust variance adjustment for expressing the results in the prevalence ratio (PR) and confidence intervals of 95% were used. The chances of presenting problems of hyperactivity were 1.42 (95% CI 1.10 to 1.83) times higher in the intermediate tercile and 1.37 (95% CI 1.06-1.78) in the higher tercile compared with the lower tercile. With respect to relationship problems the chances were of 1.49 (95% CI 1.15 to 1.93) times higher in the higher tercile when compared with the lower tercile. The results suggest that environmental factors may be strongly related to the etiology of mental disorders in childhood and adolescence. PMID- 26132256 TI - [The inclusion of sexuality as an essential aspect of comprehensive care for individuals with mental disorders]. AB - The scope of this study was to understand the representations of mental health service patients and professionals concerning the sexuality of the former. Thirty nine patients and 54 professionals of the public mental health services, divided up into six focal groups, were interviewed individually. Data analysis was based on the Structural Analysis of Narrative technique. Individuals with mental disorders do not perceive sexual health as a right and have difficulty taking care of themselves in the face of gender stereotypes, and for the contexts related with exclusion and poverty. Among the mental health service professionals, sexuality negation of mentally-ill individuals had been the commom representation. They classify this behavior as "not a normal representation" and believe that it must be restrained. Dialogues about sexuality with users are almost inexistent. Mental health service professionals are not prepared for integral assistance, which requires permanent qualification and the inclusion of this subject in the fundamental formation of health related careers, in a interdisciplinary way. PMID- 26132257 TI - Guardianship Councilors' views on the effectiveness of the existing network in providing full protection to children and teenagers in situations of sexual violence. AB - This article aimed to ascertain the point of view of Guardianship Councilors about the main difficulties of operation and mobilization faced by the Guardianship Councils network in ensuring full protection to children and teenagers in a situation of sexual abuse and exploitation in the municipality of Rio de Janeiro. The qualitative study, based on thematic analysis of 12 interviews (with individuals and as focus groups), reconstituted the scenario reported by the Councilors and the limitations that they experienced on their sphere of activity. The results indicate the following problems perceived: (i) insufficiency of institutions for specialized care; (ii) professionals without the necessary training/experience; (iii) delays; and (iv) lack of communication and coordination between institutions able to ensure the necessary protection measures for the cases concerned. PMID- 26132258 TI - Dynamics of intergenerational family relationships from the viewpoint of elderly residents in the city of Jequie (Bahia), Brazil. AB - This study aimed to describe the dynamics of intergenerational family relationships from the viewpoint of the elderly. It is a study of qualitative approach, developed with 32 elderly people registered in the coverage area of a Family Health Program in a city in the state of Bahia. Data were collected through semi-structured interviews during the first half of 2013, through home visits. We applied to thematic content analysis, and four categories emerged: harmonic intergenerational family relationships; conflicting intergenerational family relationships; family relationships permeated by intergenerational carefor the elderly; intergenerational relationships permeated by elderly caring for their grandchildren. The categories enabled an understanding of the dynamics of intergenerational family relationships from the viewpoint of elderly, unveiling family relationships guided in the care, support, family unity and even conflicts. PMID- 26132259 TI - HIV infection in male adolescents: a qualitative study. AB - 'The gradual reduction in the incidence of AIDS among men who have sex with men has not occurred in the youngest age group; on the contrary, it is growing. This paper examines the vulnerabilities of adolescent males at risk of HIV infection. This is a qualitative study conducted through interviews with HIV positive young men undergoing treatment, whose diagnosis was made during adolescence. The interviews were recorded and transcribed in full. They were analyzed by intensive reading, classified by issues, and interpreted from a hermeneutic-dialectic perspective in dialogue with the literature. We interviewed 16 young men whose diagnosis occurred between the ages of 11 and 19 and for all of them the method of HIV transmission was sexual; 12 of the men were homosexual and 4 were heterosexual. It was evident that vulnerable situations included disbelief in the possibility of contamination, subjection to sex, homophobia and commercial sexual exploitation. This study demonstrates the importance of the formulation of public policies on sexual and reproductive health, which include adolescents and young men. These policies should embody the perspective of masculinity in all its widest aspects, as well as actions in favor of sexual diversity. PMID- 26132260 TI - A decision-support tool for the control of urban noise pollution. AB - Improving the quality of life is increasingly seen as an important urban planning goal. In order to reach it, various tools are being developed to mitigate the negative impacts of human activities on society. This paper develops a methodology for quantifying the population's exposure to noise, by proposing a classification of urban blocks. Taking into account the vehicular flow and traffic composition of the surroundings of urban blocks, we generated a noise map by applying a computational simulation. The urban blocks were classified according to their noise range and then the population was estimated for each urban block, by a process which was based on the census tract and the constructed area of the blocks. The acoustical classes of urban blocks and the number of inhabitants per block were compared, so that the population exposed to noise levels above 65 dB(A) could be estimated, which is the highest limit established by legislation. As a result, we developed a map of the study area, so that urban blocks that should be priority targets for noise mitigation actions can be quickly identified. PMID- 26132261 TI - [Women's experiences and care practices in the cancer treatment process]. AB - This article seeks to understand the viewpoint of cancer patients about the disease process and the therapeutic procedures that they experience. Cancer treatments provoke a series of physical and emotional consequences in patients. Thus, patients undergo a restructuring of life and establish mechanisms to "take care of themselves." The methodology used was an ethnographic approach through interviews, field notes and participant observation. The ethnographic approach revealed how these women being given conventional treatment in a given hospital create shared care technologies based on sociability. PMID- 26132262 TI - [Determinants of active aging according to quality of life and gender]. AB - The scope of this study was to construct an indicator of active aging and assess its association with quality of life and possible determinants according to gender. The AGEQOL (Aging, Gender and Quality of Life) study was used to interview 2052 individuals aged 60 years and older residing in Sete Lagoas in the State of Minas Gerais. The association between active aging, quality of life and possible determinants was performed by multiple logistic regression with a 5% level of statistical significance separately for each gender. Most men were in the active aging group (58%), and 51.8% of women were in the normal aging group (p < 0.001). The quality of life in the Physical, Psychological, and total Score domains remained associated with the outcome in the final model for both genders. Among the men, the behavioral and community participation factors were positive predictors of active aging. Women with higher incomes, who did not suffer falls and engaged in community participation, had a better chance of belonging to the active aging group. The conclusion drawn is that quality of life and participation in groups are the main determinants of active aging, and the other factors associated with active aging are different for each gender. PMID- 26132263 TI - Greater access to information on how to prevent oral cancer among elderly using primary health care. AB - Educative actions are an important component of health promotion in Brazil's primary healthcare program, the Family Health Strategy (FHS). The efficacy of these actions is evidenced by compliance with healthy behaviors and in the reduction of rates of mortality and morbidity. The objective of this study was to identify whether access to information regarding the prevention of oral cancer is greater among elders whose residences are registered with the FHS. SPSS(r) was utilized to obtain estimates that were corrected for sample design, considering the magnitude of the associations between access to such information with personal determinants, the use and cost of healthcare, health-related behaviors and health outcomes. 58.9% of the 492 participating elders reported having access to such information. We verified that there was a greater chance for access among residents of houses registered by the FHS; those with greater per capita income (2.01/1.183.43); non-smokers (2.00/1.16-3.46); those that realized oral self examination (6.35/3.46-11.64); and those that did not perceive discomfort in the mouth, head or neck (2.06/1.02-4.17). Access was greater among residents of homes registered by the FHS. Personal determinants of health, health-related behaviors and health outcomes are influenced or influence access to information regarding the prevention and management of oral diseases. PMID- 26132264 TI - The permanent relation between biology, power and war: the dual use of the biotechnological development. AB - Throughout the twentieth century, the biological advance had a closer and closer relation with the strategies of power in search of high technology. From 1970, the manipulation of genetically recombined pathogenic agents was a high technological breakthrough that radically over passed traditional biology and reinforced the war relations of science. The biotechnological revolution started along with new perspectives for the political and military field of science. From this point of the biotechnological development a new paradigm for war, as well as for the sciences of life, was then created and new challenges for International Health in the twenty first century came into scene. Through a historical account related to power, this paper is meant to present the mechanism of articulation existent between science and power and to contribute for understanding how the military field is naturally inserted in the biotechnological development which, in its essence, produces biotechnologies for civil and military uses. PMID- 26132265 TI - Best practices in school food and nutrition units of public schools of Bayeux, PB, Brazil. AB - The occurrence of foodborne illness outbreaks is increasing in schools, and due to the number of children who consume school meals as the only daily meal, this factor becomes even more worrisome. In this sense, the aim of this study was to evaluate the hygienic-health aspects of Food and Nutrition Units (SFNU) of public schools of Bayeux / PB in relation to the adoption of best practices in school food and nutrition. Data were collected through SFNU checklist during visits to units in 29 schools. The health risk of units evaluated was from regular to very high regarding structure and facilities, hygiene of food handlers, environment and food preparation. It was found that 10.3% of handlers used clean and adequate uniforms, and environment and equipment showed poor conservation status in 75.9% and 89.7% of Units, respectively; control of urban pests and vectors was not effective and cleaning of fresh produce was incorrectly conducted in 51.7% of SFNU of schools evaluated. It could be concluded that the production of meals in SFNU of schools evaluated does not meet the requirements established by the best practices in school food and nutrition. PMID- 26132266 TI - Pathways for graduation evaluation in Dentistry: logical model building and validation criteria. AB - The need for universal access to health care and the failure of the pedagogical model centered on only the transmission of knowledge has led to changes in the training of health professionals. The aim of this study was to provide a new alternative for evaluation of Dentistry courses based on the National Curriculum Guidelines (NCG) of the area. For this, a logical model was formulated on the need for training in the oral health pathway which allowed for the construction of a criteria matrix, validated by Delphi consensus technique and modified by the participation of 33 "experts." The matrix dimensions presented as a pedagogical approach the profile of graduates, the teaching-service integration and orientation of health care. The detailing of these dimensions into sub-dimensions and of measurable criteria allowed for deepening structural elements of the NCG unexplored in other studies evaluating undergraduate courses in Dentistry. The final instrument proposed in this study is differentiated alternative assessment training, for both dentists and other professionals, considering that the NCG of all healthcare courses provide for the training focused on the health needs of the population, integrated to Unified Health System (SUS) and based on student centered learning. PMID- 26132268 TI - Regime Shift in an Exploited Fish Community Related to Natural Climate Oscillations. AB - Identifying the various drivers of marine ecosystem regime shifts and disentangling their respective influence are critical tasks for understanding biodiversity dynamics and properly managing exploited living resources such as marine fish communities. Unfortunately, the mechanisms and forcing factors underlying regime shifts in marine fish communities are still largely unknown although climate forcing and anthropogenic pressures such as fishing have been suggested as key determinants. Based on a 24-year-long time-series of scientific surveys monitoring 55 fish and cephalopods species, we report here a rapid and persistent structural change in the exploited fish community of the eastern English Channel from strong to moderate dominance of small-bodied forage fish species with low temperature preferendum that occurred in the mid-1990s. This shift was related to a concomitant warming of the North Atlantic Ocean as attested by a switch of the Atlantic Multidecadal Oscillation from a cold to a warm phase. Interestingly, observed changes in the fish community structure were opposite to those classically induced by exploitation as larger fish species of higher trophic level increased in abundance. Despite not playing a direct role in the regime shift, fishing still appeared as a forcing factor affecting community structure. Moreover, although related to climate, the regime shift may have been facilitated by strong historic exploitation that certainly primed the system by favoring the large dominance of small-bodied fish species that are particularly sensitive to climatic variations. These results emphasize that particular attention should be paid to multidecadal natural climate variability and its interactions with both fishing and climate warming when aiming at sustainable exploitation and ecosystem conservation. PMID- 26132269 TI - Pentafluoroethyl-substituted alpha-silanes: model compounds for new insights. AB - To further investigate the alpha-effect in silanes bearing a geminal donor atom, the model compounds (C2F5)3SiCH2NMe2, (C2F5)3SiCH2OMe and (C2F5)3SiONMe2 were prepared by introduction of pentafluoroethyl groups via nucleophilic substitution of the corresponding chloro-derivatives with pentafluoroethyl lithium. The substances were characterised by NMR spectroscopy and X-ray diffraction via in situ crystallization techniques. The solid state structures of these highly electronegatively substituted alpha-silanes contain monomeric molecules. The Si-C N angle in (C2F5)3SiCH2NMe2 shows a value of 115.3(2) degrees and the Si-C-O angle in (C2F5)3SiCH2OMe a value of 105.4(1) degrees . Both values are smaller than the Si-C-C angle of the reference compound (C2F5)3SiCH2CH3 with a value of 118.6(2) degrees indicating attractive interaction between the silicon atom and the respective donor atoms. The Si-O-N angle in (C2F5)3SiONMe2 is extremely narrow at 82.0(1) degrees . This behaviour was further investigated by gas electron diffraction and by quantum-chemical calculations. The NBO method finds no significant orbital interactions between Si and N/O atoms in the Si-C-N, Si-C O and Si-O-N units. The IQA model describes the compounds as strongly stabilised by electrostatic interactions between formally non-bonded silicon and donor atoms. PMID- 26132270 TI - Computational Model of Primary Visual Cortex Combining Visual Attention for Action Recognition. AB - Humans can easily understand other people's actions through visual systems, while computers cannot. Therefore, a new bio-inspired computational model is proposed in this paper aiming for automatic action recognition. The model focuses on dynamic properties of neurons and neural networks in the primary visual cortex (V1), and simulates the procedure of information processing in V1, which consists of visual perception, visual attention and representation of human action. In our model, a family of the three-dimensional spatial-temporal correlative Gabor filters is used to model the dynamic properties of the classical receptive field of V1 simple cell tuned to different speeds and orientations in time for detection of spatiotemporal information from video sequences. Based on the inhibitory effect of stimuli outside the classical receptive field caused by lateral connections of spiking neuron networks in V1, we propose surround suppressive operator to further process spatiotemporal information. Visual attention model based on perceptual grouping is integrated into our model to filter and group different regions. Moreover, in order to represent the human action, we consider the characteristic of the neural code: mean motion map based on analysis of spike trains generated by spiking neurons. The experimental evaluation on some publicly available action datasets and comparison with the state-of-the-art approaches demonstrate the superior performance of the proposed model. PMID- 26132271 TI - The Role of the Radial Margin: Further Call for Standardization of Colon Cancer Care. PMID- 26132272 TI - The magnetic anal sphincter: a seductive promise still not kept. PMID- 26132273 TI - Structure-Based Development of a Protein-Protein Interaction Inhibitor Targeting Tumor Necrosis Factor Receptor-Associated Factor 6. AB - The interactions between tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and TNF superfamily receptors (TNFRSFs) are promising targets for rheumatoid arthritis (RA) treatment. However, due to the challenging nature of protein-protein interactions (PPIs), a potent inhibitor that surpasses the affinity of the TRAF6-TNFRSF interactions has not been developed. We developed a small-molecule PPI inhibitor of TRAF6-TNFRSF interactions using NMR and in silico techniques. The most potent compound, TRI4, exhibited an affinity higher than those of TNFRSFs and competitively inhibited a TRAF6-TNFRSF interaction. Structural characterization of the TRAF6-TRI4 complex revealed that TRI4 supplants key interactions in the TRAF6-TNFRSF interfaces. In addition, some TRAF6-TRI4 interactions extend beyond the TRAF6-TNFRSF interfaces and increase the binding affinity. Our successful development of TRI4 provides a new opportunity for RA treatment and implications for structure-guided development of PPI inhibitors. PMID- 26132274 TI - A new 9,10-dihydrophenanthrene from Dendrobium moniliforme. AB - A new 9,10-dihydrophenanthrene,1,5-dihydroxy-3,4,7-trimethoxy-9,10 dihydrophenanthrene (1) was isolated and identified from the whole plants of Dendrobium moniliforme, as well as 24 known compounds including hircinol (2), (2R*,3S*)-3-hydroxymethyl-9-methoxy-2-(4'-hydroxy-3',5'-dimethoxyphenyl)-2,3,6,7 tetrahydro-phenanthro[4,3-b]furan-5,11-diol (3), diospyrosin (4), aloifol I (5), moscatilin (6), 3,4'-dihydroxy-3',4,5-trimethoxybibenzyl (7), gigantol (8), 3,3' dihydroxy-4,5-dimethoxybibenzyl (9), longicornuol A (10), N-trans cinnamoyltyramine (11), paprazine (12), N-trans-feruloyl 3'-O-methyldopamine (13), moupinamide (14), dihydroconiferyl dihydro-p-coumarate (15), dihydrosinapyl dihydro-p-coumarate (16), 3-isopropyl-5-acetoxycyclohexene-2-one-1 (17), p hydroxybenzaldehyde (18), vanillin (19), p-hydroxyphenylpropionic acid (20), vanillic acid (21), protocatechuic acid (22), (+)-syringaresinol (23), beta sitosterol (24) and daucosterol (25). Compounds 3, 4, 13, 16, 17 and 20 were isolated from the Dendrobium genus for the first time, and compounds 2, 5, 7, 9 12, 14, 15, 18, 21 and 22 were originally obtained from D. moniliforme. PMID- 26132275 TI - Potentiation of Glibenclamide Hypoglycaemia in Mice by MK-467, a Peripherally Acting Alpha2-Adrenoceptor Antagonist. AB - Pharmacological antagonism and genetic depletion of pancreatic alpha2A adrenoceptors increase insulin secretion in mice and enhance the insulinotropic action of glibenclamide, a representative of the sulphonylurea class of insulin secretagogues used in the therapy of type 2 diabetes. Antagonism of alpha2 adrenoceptors in the central nervous system (CNS) causes tachycardia and hypertension, making generalized alpha2-adrenoceptor blockade unfavourable for clinical use despite its potential to decrease blood glucose levels. The purpose of this study was to test the acute effects of the peripherally acting alpha2 adrenoceptor antagonist MK-467 alone and in combination with glibenclamide in non diabetic C57BL/6N mice. Cardiovascular safety was assessed in freely moving mice with radiotelemetry. Dose-dependent decreases in blood glucose and increases in plasma insulin concentrations were seen with the combination of MK-467 and glibenclamide; the combinations were much more potent than glibenclamide or MK 467 alone. Furthermore, MK-467 had no effect on mean arterial pressure or heart rate in freely moving mice and did not prevent the centrally mediated hypotensive effect of the alpha2-adrenoceptor agonist medetomidine. Thus, peripheral blockade of alpha2-adrenoceptors does not evoke the same cardiovascular adverse effects as antagonism of CNS alpha2-adrenoceptors. The current results indicate that the combined use of small doses of a peripherally acting alpha2-adrenoceptor antagonist with a sulphonylurea drug could provide a novel option for the treatment of type 2 diabetes, especially in patients with increased tonic alpha2 adrenoceptor-mediated inhibition of insulin secretion. PMID- 26132276 TI - CR3 and Dectin-1 Collaborate in Macrophage Cytokine Response through Association on Lipid Rafts and Activation of Syk-JNK-AP-1 Pathway. AB - Collaboration between heterogeneous pattern recognition receptors (PRRs) leading to synergistic coordination of immune response is important for the host to fight against invading pathogens. Although complement receptor 3 (CR3) and Dectin-1 are major PRRs to detect fungi, crosstalk between these two receptors in antifungal immunity is largely undefined. Here we took advantage of Histoplasma capsulatum which is known to interact with both CR3 and Dectin-1 and specific particulate ligands to study the collaboration of CR3 and Dectin-1 in macrophage cytokine response. By employing Micro-Western Array (MWA), genetic approach, and pharmacological inhibitors, we demonstrated that CR3 and Dectin-1 act collaboratively to trigger macrophage TNF and IL-6 response through signaling integration at Syk kinase, allowing subsequent enhanced activation of Syk-JNK-AP 1 pathway. Upon engagement, CR3 and Dectin-1 colocalize and form clusters on lipid raft microdomains which serve as a platform facilitating their cooperation in signaling activation and cytokine production. Furthermore, in vivo studies showed that CR3 and Dectin-1 cooperatively participate in host defense against disseminated histoplasmosis and instruct adaptive immune response. Taken together, our findings define the mechanism of receptor crosstalk between CR3 and Dectin-1 and demonstrate the importance of their collaboration in host defense against fungal infection. PMID- 26132277 TI - Impact of diabetes on cognitive function and brain structure. AB - Both type 1 and type 2 diabetes have been associated with reduced performance on multiple domains of cognitive function and with structural abnormalities in the brain. With an aging population and a growing epidemic of diabetes, central nervous system-related complications of diabetes are expected to rise and could have challenging future public health implications. In this review, we will discuss the brain structural and functional changes that have been associated with type 1 and type 2 diabetes. Diabetes duration and glycemic control may play important roles in the development of cognitive impairment in diabetes, but the exact underlying pathophysiological mechanisms causing these changes in cognition and structure are not well understood. Future research is needed to better understand the natural history and the underlying mechanisms, as well as to identify risk factors that predict who is at greatest risk of developing cognitive impairment. This information will lead to the development of new strategies to minimize the impact of diabetes on cognitive function. PMID- 26132278 TI - Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus. AB - Alzheimer's disease is a neurodegenerative disease affecting the aging population. A key neuropathological feature of the disease is the over-production of amyloid-beta and the deposition of amyloid-beta plaques in brain regions of the afflicted individuals. Throughout the years scientists have generated numerous Alzheimer's disease mouse models that attempt to replicate the amyloid beta pathology. Unfortunately, the mouse models only selectively mimic the disease features. Neuronal death, a prominent effect in the brains of Alzheimer's disease patients, is noticeably lacking in these mice. Hence, we and others have employed a method of directly infusing soluble oligomeric species of amyloid-beta - forms of amyloid-beta that have been proven to be most toxic to neurons - stereotaxically into the brain. In this report we utilize male C57BL/6J mice to document this surgical technique of increasing amyloid-beta levels in a select brain region. The infusion target is the dentate gyrus of the hippocampus because this brain structure, along with the basal forebrain that is connected by the cholinergic circuit, represents one of the areas of degeneration in the disease. The results of elevating amyloid-beta in the dentate gyrus via stereotaxic infusion reveal increases in neuron loss in the dentate gyrus within 1 week, while there is a concomitant increase in cell death and cholinergic neuron loss in the vertical limb of the diagonal band of Broca of the basal forebrain. These effects are observed up to 2 weeks. Our data suggests that the current amyloid beta infusion model provides an alternative mouse model to address region specific neuron death in a short-term basis. The advantage of this model is that amyloid-beta can be elevated in a spatial and temporal manner. PMID- 26132280 TI - Differences Between New Immigrants From the Former Soviet Union and Veteran Residents in Knowledge, Perception, and Risk Factors of Stroke. AB - BACKGROUND: Stroke is the fourth most common cause of death in developed countries and a leading cause of acquired disability in adults. Awareness of risk factors and warning signs for stroke has a considerable impact on early arrival at the hospital and early thrombolytic treatment. Delays in seeking medical treatment following the onset of stroke symptoms have been shown to be more common among ethnic minorities. OBJECTIVE: The aim of the current study was to examine stroke awareness and knowledge among new immigrants from the Former Soviet Union (IFSUs) compared with veteran residents (VRs). METHODS: The study was conducted by students of the nursing master of arts program. Data were collected during March 2010 and June 2014. Trained registered nurses conducted interviews, using a structured, pretested, open-ended questionnaire. Participants were recruited by a snowball method from among the interviewers' friends and family members, 40 years or older with no history of stroke. RESULTS: A total of 643 Israelis, 420 VRs (65.3%) and 223 IFSUs (34.7%), were interviewed; 40.7% were men, with a mean age of 52.6 (SD, 9.3) years. Compared with VRs, IFSUs were more likely to report previous myocardial infarction (P = .022), hypertension (P < .001), and diabetes (P = .012). The mean number of stroke warning signs reported by IFSUs was higher than that reported by VRs (P = .031). When asked about risk factors for stroke, IFSUs more often stated hypertension (P = .03), whereas VRs more often reported family history (P = .03). Immigrants from the Former Soviet Union were more aware of strategies for the prevention of stroke than VRs (P = .02). The preferred sources of information about stroke for IFSUs, as distinguished from VRs, were personal doctors (P = .001) and radio programs (P = .03). CONCLUSIONS: Veteran residents showed lower levels of knowledge about stroke. Educational campaigns aimed at increasing knowledge of stroke among Israel's general population in Israel, as well as culturally targeting specific subgroups, are recommended. PMID- 26132279 TI - Cognitive Function Does Not Impact Self-reported Health-Related Quality of Life in Heart Failure Patients. AB - BACKGROUND: Adults with heart failure (HF) often demonstrate impairment across multiple domains of cognitive functioning and report poor health-related quality of life (HRQoL). Previous researchers have found that cognitive deficits were generally not associated with HRQoL in a carefully evaluated sample. The exception was memory, which was only weakly associated with HRQoL. However, cognitive deficits interfere with self-care and disease self-management, which could be expected to affect HRQoL. OBJECTIVE: We sought to verify this counterintuitive finding in a large well-characterized sample of HF patients using a well-validated neuropsychological battery. METHODS: Participants were 302 adults (63% male) predominately white (72.5%) HF patients (68.7 +/- 9.6 years) recruited from 2 medical centers. Self-reported HRQoL was assessed using the Kansas City Cardiomyopathy Questionnaire. Participants completed a neuropsychological battery examining attention, executive function, memory, and visuospatial functioning. Hierarchical multiple linear regression was used for analyses. RESULTS: Mild global cognitive impairment was observed in 29.5% of the sample (Modified Mini-Mental State [3MS] Examination score <90). Controlling for gender, depression, HF severity, premorbid IQ, comorbidities, and education, only executive function predicted HRQoL, beta = .17, P < .05. However, executive function accounted for only 0.6% of the variance in HRQoL. CONCLUSION: Cognitive function generally did not predict HRQoL in HF patients. The correlates of HRQoL in HF do not appear to include mild cognitive impairment. Other factors may play a bigger role such as disease severity, age, and depressive symptoms. Future studies should investigate modifiable determinants of HRQoL in HF patients, toward the goal of finding interventions that preserve HRQoL during this chronic illness. PMID- 26132281 TI - Experiences of Young Adults With Pacemakers and/or Implantable Cardioverter Defibrillators. AB - BACKGROUND: The number of implanted devices (pacemakers [PMs] and implantable cardioverter defibrillators [ICDs]) is increasing. Because of technological advances, these devices are used in greater numbers in children and adolescents. Challenges of having these devices have been well studied in adults, but little is known about the lived experiences from the perspective of young adults. OBJECTIVE: This study explored the lived experiences, coping behaviors, and challenges of young adults who had cardiac devices implanted during childhood. METHODS: A descriptive qualitative study design was used. Purposive sampling was used to identify young adults aged 18 to 29 years, living with a PM and/or ICD. Participants were interviewed about their experiences and challenges related to living with a PM or ICD, with common themes identified and analyzed. RESULTS: A total of 6 participants were interviewed for this study. The challenges of living with a PM and/or ICD included insecurity about physical appearance, device compliance, physical sensations of the device, future uncertainty, and limited support. The identified coping behaviors utilized by the participants were confrontation, acceptance, educating others, spreading awareness, avoidance, and humor. The overall lived experiences described were appreciation for device benefits, fear of device malfunction, and attracting attention. CONCLUSIONS: The lived experiences of young recipients often mirror that of older adults; however, it is clear that there are challenges and coping behaviors unique to young adults living with a PM and/or ICD. It is important to educate healthcare providers about the unique challenges that young adults may face so they can provide the appropriate support to this population. PMID- 26132282 TI - HIV and coronary arterial remodeling from the Multicenter AIDS Cohort Study (MACS). AB - OBJECTIVE: Positive remodeling (PR), a coronary artery characteristic associated with risk for myocardial infarction (MI), may be more prevalent in HIV-infected (HIV+) people. We evaluated the prevalence of PR using coronary CT angiography (CCTA) in HIV+ and HIV-uninfected (HIV-) men. METHODS: Men enrolled in the Multicenter AIDS Cohort Study underwent CCTA if they were 40-70 years, had normal kidney function and no history of coronary revascularization. Multivariable logistic regression models were used to estimate the odds ratio (OR) of PR by HIV serostatus, adjusting for demographics and coronary artery disease (CAD) risk factors. Analysis of PR among atherosclerotic segments further adjusted for plaque type and stenosis. RESULTS: The prevalence of PR was 8.4% versus 12.1% (p = 0.10) for HIV- and HIV + men, respectively. After demographic adjustment, HIV + men had twice the odds of PR [OR 2.01(95% CI 1.20-3.38)], which persisted after CAD risk factor adjustment [1.76(1.00-3.10)]. Higher systolic blood pressure, total cholesterol, diabetes medication use, older age, segment number with plaque present, mixed and non-calcified plaque, and stenosis>50%, were associated with increased odds of PR, while higher HDL cholesterol, higher nadir CD4 count, and black race were associated with lower PR odds. Among atherosclerotic segments, the association between HIV infection and PR persisted, but was not statistically significantly. CONCLUSION: HIV+ men have more positively remodeled arterial segments, which may be due to more coronary segments with atherosclerosis or HIV related immunosuppression. Further studies are needed to evaluate whether PR contributes to higher rates of MI in HIV+ individuals. PMID- 26132284 TI - Letter: WEB Aneurysm Treatment: Occlusion Stability and "Compression". PMID- 26132283 TI - Neutrophil count improves the GRACE risk score prediction of clinical outcomes in patients with ST-elevation myocardial infarction. AB - OBJECTIVE: Both the Global Registry of Acute Coronary Events (GRACE) risk score and neutrophil count could predict clinical outcomes in patients with acute coronary syndromes. However, the ability of them to identify high risk patients leaves room for improvement. The purpose of the present study was to evaluate whether the combination of them could have a better performance in predicting clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). METHODS: A total of 1287 consecutive STEMI patients were recruited at two centers in China. Neutrophil count was measured and the GRACE risk score was calculated. RESULTS: During a median period of 37 months (IQR, 29-47), 135 (10.9%) patients had major adverse cardiovascular events (MACE), including 116 all-cause death. Neutrophil count and the GRACE risk score were higher in patients with MACE. Both neutrophil count and the GRACE score were significant and independent predictors for MACE [HR: 1.260 (1.203-1.319), P < 0.001; HR: 1.007 (1.002-1.011), P < 0.001; respectively). Combination of them increased the area under the ROC (0.698 vs. 0.796, P < 0.001). The addition of neutrophil count to GRACE model enhanced net reclassification improvement (0.637, P = 0.020) and integrated discrimination improvement (0.180, P < 0.001), suggesting effective discrimination and reclassification. CONCLUSION: Both neutrophil count and the GRACE risk score are independent predictors for MACE in patients with STEMI. A combination of them could derive a more accurate prediction for clinical outcomes in these patients. PMID- 26132285 TI - In Reply: WEB Aneurysm Treatment: Occlusion Stability and "Compression". PMID- 26132286 TI - Successful Working Memory Processes and Cerebellum in an Elderly Sample: A Neuropsychological and fMRI Study. AB - BACKGROUND: Imaging studies help to understand the evolution of key cognitive processes related to aging, such as working memory (WM). This study aimed to test three hypotheses in older adults. First, that the brain activation pattern associated to WM processes in elderly during successful low load tasks is located in posterior sensory and associative areas; second, that the prefrontal and parietal cortex and basal ganglia should be more active during high-demand tasks; third, that cerebellar activations are related to high-demand cognitive tasks and have a specific lateralization depending on the condition. METHODS: We used a neuropsychological assessment with functional magnetic resonance imaging and a core N-back paradigm design that was maintained across the combination of four conditions of stimuli and two memory loads in a sample of twenty elderly subjects. RESULTS: During low-loads, activations were located in the visual ventral network. In high loads, there was an involvement of the basal ganglia and cerebellum in addition to the frontal and parietal cortices. Moreover, we detected an executive control role of the cerebellum in a relatively symmetric fronto-parietal network. Nevertheless, this network showed a predominantly left lateralization in parietal regions associated presumably with an overuse of verbal storage strategies. The differential activations between conditions were stimuli-dependent and were located in sensory areas. CONCLUSION: Successful WM processes in the elderly population are accompanied by an activation pattern that involves cerebellar regions working together with a fronto-parietal network. PMID- 26132287 TI - Neurocysticercotic Calcifications and Hippocampal Sclerosis: A Case-Control Study. AB - OBJECTIVE: The exact role of calcified neurocysticercotic lesions (CNLs) in epilepsy is yet unknown and controversial. Although the relationship between CNLs, epilepsy and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE HS) has already been addressed, to our knowledge, no study has actually provided strong statistical evidence, nor reported the ODDS ratio for these associations. Therefore, we designed this case-control study to assess the likelihood of having MTLE-HS versus other forms of epilepsy in the presence of CNLs. METHODS: In this case-control study we included 119 consecutive patients with epilepsy and 106 disease controls (headache) with previous CT scans. We subdivided cases into MTLE HS and other epilepsies. We used brain CT scans to define presence or absence of CNLs. After exploratory analyses, we used logistic regression to analyze the association between CNLs, epilepsy subgroups and disease controls. RESULTS: CNLs were found in 31.09% of cases and in 11.32% of controls (p<0.001). The initial analysis comparing epilepsy versus controls revealed a significant association between CNLs and epilepsy (OR = 5.32; 95%CI = 2.43-11.54; p<0.001). However, when we compared MTLE-HS versus other epilepsies versus controls we confirmed that CNLs were associated with MTLE-HS (OR = 11.27, 95%CI = 4.73-26.85; p<0.001) but other epilepsies were not. We found no difference in the CNLs load and no difference in the location of the CNLs when we compared patients with MTLE-HS, other epilepsies and disease controls. SIGNIFICANCE: The inclusion of controls allowed us to estimate the likelihood of having epilepsy in the presence of CNLs. We found that patients with CNLs were 11 times more likely to have MTLE-HS; however, the presence of CNLs did not change the odds of having other types of epilepsy. These findings raise the possibility of neurocysticercosis playing a role in the pathophysiology of MTLE-HS and need further confirmation in other series. PMID- 26132288 TI - Improvement of Cell Survival During Human Pluripotent Stem Cell Definitive Endoderm Differentiation. AB - Definitive endoderm (DE) is a vital precursor for internal organs such as liver and pancreas. Efficient protocol to differentiate human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) to DE is essential for regenerative medicine and for modeling diseases; yet, poor cell survival during DE differentiation remains unsolved. In this study, our use of B27 supplement in modified differentiation protocols has led to a substantial improvement. We used an SOX17-enhanced green fluorescent protein (eGFP) reporter hESC line to compare and modify established DE differentiation protocols. Both total live cell numbers and the percentages of eGFP-positive cells were used to assess differentiation efficiency. Among tested protocols, three modified protocols with serum-free B27 supplement were developed to generate a high number of DE cells. Massive cell death was avoided during DE differentiation and the percentage of DE cells remained high. When the resulting DE cells were further differentiated toward the pancreatic lineage, the expression of pancreatic-specific markers was significantly increased. Similar high DE differentiation efficiency was observed in H1 hESCs and iPSCs through the modified protocols. In B27 components, bovine serum albumin was found to facilitate DE differentiation and cell survival. Using our modified DE differentiation protocols, satisfactory quantities of quality DE can be produced as primary material for further endoderm lineage differentiation. PMID- 26132289 TI - RM1 Semiempirical Quantum Chemistry: Parameters for Trivalent Lanthanum, Cerium and Praseodymium. AB - The RM1 model for the lanthanides is parameterized for complexes of the trications of lanthanum, cerium, and praseodymium. The semiempirical quantum chemical model core stands for the [Xe]4fn electronic configuration, with n =0,1,2 for La(III), Ce(III), and Pr(III), respectively. In addition, the valence shell is described by three electrons in a set of 5d, 6s, and 6p orbitals. Results indicate that the present model is more accurate than the previous sparkle models, although these are still very good methods provided the ligands only possess oxygen or nitrogen atoms directly coordinated to the lanthanide ion. For all other different types of coordination, the present RM1 model for the lanthanides is much superior and must definitely be used. Overall, the accuracy of the model is of the order of 0.07A for La(III) and Pr(III), and 0.08A for Ce(III) for lanthanide-ligand atom distances which lie mostly around the 2.3A to 2.6A interval, implying an error around 3% only. PMID- 26132290 TI - Response to "Comment on 'Association between Lifetime Exposure to Inorganic Arsenic in Drinking Water and Coronary Heart Disease in Colorado Residents'". PMID- 26132291 TI - The Challenges of Afghanistan and Iraq Veterans' Transition from Military to Civilian Life and Approaches to Reconnection. AB - Afghanistan and Iraq veterans experienced traumas during deployment, and disrupted connections with friends and family. In this context, it is critical to understand the nature of veterans' transition to civilian life, the challenges navigated, and approaches to reconnection. We investigated these issues in a qualitative study, framed by homecoming theory, that comprised in-depth interviews with 24 veterans. Using an inductive thematic analysis approach, we developed three overarching themes. Military as family explored how many veterans experienced the military environment as a "family" that took care of them and provided structure. Normal is alien encompassed many veterans experiences of disconnection from people at home, lack of support from institutions, lack of structure, and loss of purpose upon return to civilian life. Searching for a new normal included strategies and supports veterans found to reconnect in the face of these challenges. A veteran who had successfully transitioned and provided support and advice as a peer navigator was frequently discussed as a key resource. A minority of respondents-those who were mistreated by the military system, women veterans, and veterans recovering from substance abuse problems were less able to access peer support. Other reconnection strategies included becoming an ambassador to the military experience, and knowing transition challenges would ease with time. Results were consistent with and are discussed in the context of homecoming theory and social climate theory. Social support is known to be protective for veterans, but our findings add the nuance of substantial obstacles veterans face in locating and accessing support, due to disconnection and unsupportive institutions. Larger scale work is needed to better understand how to foster peer connection, build reconnection with family, and engage the broader community to understand and support veterans; interventions to support reconnection for veterans should be developed. PMID- 26132292 TI - Novel CYP27B1 Gene Mutations in Patients with Vitamin D-Dependent Rickets Type 1A. AB - The CYP27B1 gene encodes 25-hydroxyvitamin D-1alpha-hydroxylase. Mutations of this gene cause vitamin D-dependent rickets type 1A (VDDR-IA, OMIM 264700), which is a rare autosomal recessive disorder. To investigate CYP27B1 mutations, we studied 8 patients from 7 unrelated families. All coding exons and intron-exon boundaries of CYP27B1 gene were amplified by PCR from peripheral leukocyte DNA and subsequently sequenced. Homozygous mutations in the CYP27B1 gene were found in all the patients and heterozygous mutations were present in their normal parents. One novel single nucleotide variation (SNV, c.1215 T>C, p.R379R in the last nucleotide of exon 7) and three novel mutations were identified:, a splice donor site mutation (c.1215+2T>A) in intron 7, a 16-bp deletion in exon 6 (c.1022 1037del16), and a 2-bp deletion in exon 5 (c.934_935delAC). Both c.1215 T>C and c.1215+2T>A were present together in homozygous form in two unrelated patients, and caused exon 7 skipping. However, c.1215 T>C alone has no effect on pre-mRNA splicing. The skipping of exon 7 resulted in a shift of downstream reading frame and a premature stop codon 57 amino acids from L380 (p.L380Afs*57). The intra exon deletions of c.1022-1037del16 and c.934_935delAC also resulted in a frameshift and the creation of premature stop codons at p.T341Rfs*5, and p.T312Rfs*19, respectively, leading to the functional inactivation of the CYP27B1 gene. Clinically, all the patients required continued calcitriol treatment and the clinical presentations were consistent with the complete loss of vitamin D1alpha-hydroxylase activity. In conclusion, three novel mutations have been identified. All of them caused frameshift and truncated proteins. The silent c.1215 T>C SNV has no effect on pre-mRNA splicing and it is likely a novel SNP. The current study further expands the CYP27B1 mutation spectrum. PMID- 26132295 TI - New Family of Lanthanide-Based Complexes with Different Scorpionate-Type Ligands: A Rare Case Where Dysprosium and Ytterbium Analogues Display Single-Ion-Magnet Behavior. AB - A new family of lanthanide complexes [Ln(Tpz)2Bpz].xCH2Cl2 (Ln = Gd, Tb, Dy, Ho, x = 0.5; Ln = Yb, x = 1; Tpz = hydrotris(pyrazolyl)borate; Bpz = dihydrobis(pyrazolyl)borate) has been synthesized. Those complexes have been characterized by single-crystal X-ray diffraction, and the magnetic properties have been investigated. Both dysprosium and ytterbium analogues display single ion-magnet behavior, despite the difference in their spatial distribution of 4f electronic charges. Theoretical calculations with crystal field parameters have been carried out to gain better insight of the relaxation pathways that may be involved in those two complexes. PMID- 26132294 TI - Low Copy Number of the AMY1 Locus Is Associated with Early-Onset Female Obesity in Finland. AB - BACKGROUND: The salivary alpha-amylase locus (AMY1) is located in a highly polymorphic multi allelic copy number variable chromosomal region. A recent report identified an association between AMY1 copy numbers and BMI in common obesity. The present study investigated the relationship between AMY1 copy number, BMI and serum amylase in childhood-onset obesity. PATIENTS: Sixty-one subjects with a history of childhood-onset obesity (mean age 19.1 years, 54% males) and 71 matched controls (19.8 yrs, 45% males) were included. All anthropometric measures were greater in the obese; their mean BMI was 40 kg/m2 (range 25-62 kg/m2) compared with 23 kg/m2 in the controls (15-32 kg/m2). RESULTS: Mean AMY1 copy numbers did not differ between the obese and control subjects, but gender differences were observed; obese men showed the highest and obese women the lowest number of AMY1 copies (p=0.045). Further, only in affected females, AMY1 copy number correlated significantly with whole body fat percent (r=-0.512, p=0.013) and BMI (r=-0.416, p=0.025). Finally, a clear linear association between AMY1 copy number and serum salivary amylase was observed in all subgroups but again differences existed between obese males and females. CONCLUSIONS: In conclusion, our findings suggest that AMY1 copy number differences play a role in childhood-onset obesity but the effect differs between males and females. Further studies in larger cohorts are needed to confirm these observations. PMID- 26132293 TI - Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets. AB - BACKGROUND: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct. METHODS: Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large group of neuropsychiatric patients. Two groups were analyzed: Group 1 with TBI (n=104), PTSD (n=104) or both (n=73) closely matched for demographics and comorbidity, compared to each other and healthy controls (N=116); Group 2 with TBI (n=7,505), PTSD (n=1,077) or both (n=1,017) compared to n=11,147 without either. ROIs and visual readings (VRs) were analyzed using a binary logistic regression model with predicted probabilities inputted into a Receiver Operating Characteristic analysis to identify sensitivity, specificity, and accuracy. One-way ANOVA identified the most diagnostically significant regions of increased perfusion in PTSD compared to TBI. Analysis included a 10-fold cross validation of the protocol in the larger community sample (Group 2). RESULTS: For Group 1, baseline and on-task ROIs and VRs showed a high level of accuracy in differentiating PTSD, TBI and PTSD+TBI conditions. This carefully matched group separated with 100% sensitivity, specificity and accuracy for the ROI analysis and at 89% or above for VRs. Group 2 had lower sensitivity, specificity and accuracy, but still in a clinically relevant range. Compared to subjects with TBI, PTSD showed increases in the limbic regions, cingulum, basal ganglia, insula, thalamus, prefrontal cortex and temporal lobes. CONCLUSIONS: This study demonstrates the ability to separate PTSD and TBI from healthy controls, from each other, and detect their co-occurrence, even in highly comorbid samples, using SPECT. This modality may offer a clinical option for aiding diagnosis and treatment of these conditions. PMID- 26132296 TI - Thermoresponsive PDMAEMA Brushes: Effect of Gold Nanoparticle Deposition. AB - The paper addresses the effect of gold nanoparticle (Au-NP) deposition on the thermoresponsive volume phase transition of the weak polyelectrolyte poly(2 (dimethylamino)ethyl methacrylate) (PDMAEMA) brushes. PDMAEMA brushes were synthesized via surface-initiated atom transfer radical polymerization (SI-ATRP). The PDMAEMA/Au-NP composite brushes were fabricated by immersing the brush modified wafer in the Au-NP suspension. Atomic force microscopy (AFM), ellipsometry, and scanning electron microscopy (SEM) have been employed to characterize the neat PDMAEMA brushes and PDMAEMA/Au-NP composite brushes. All neat PDMAEMA brushes swelled below the volume phase transition temperature and collapsed with increasing temperature over a broad temperature range independent of the initial brush thickness. Water uptake of the brushes is also independent of initial brush thickness. The adsorption of the charged Au-NPs significantly affects the degree of swelling and the thermoresponsive properties of the brushes. PDMAEMA/Au-NP composite brushes do not exhibit any noticeable phase transition at the experimental temperature range irrespective of the initial brush thickness. The reason for this behavior is attributed to a combination of the following: the decreased conformational entropy of the Au-NP adsorbed polymer chains, the increased hydrophilicity of the system due to the charged Au-NPs, and the ~13 nm diameter Au-NPs causing steric hindrance. We have also shown that the AFM full-indentation method can be successfully applied to determine the polymer brush thicknesses. PMID- 26132297 TI - A genomic approach to alcoholism. PMID- 26132298 TI - Clinical and Demographic Characteristics of Binge Drinkers Associated with Lack of Efficacy of Brief Intervention and Medical Advice. AB - Brief Counseling Intervention (BCI) and Medical advice (MA) are psychotherapeutic approaches used for the treatment of binge drinkers in Primary Care. Although binge drinking is a common pattern of alcohol misuse in Europe and in the US, no studies have evaluated those subjects who do not respond to Brief Counseling Interventions or Medical Advice. OBJECTIVE: To determine the clinical and demographic characteristics of binge drinkers in whom BCI or MA are not effective in reducing harmful alcohol use. METHODS: This is a secondary analysis of data from a randomized alcohol brief intervention trial with a 12-month follow-up period. A total of 674 subjects (89%) participated right through to the end of the study. The primary outcome measure was change in harmful alcohol use from baseline to 12 months. RESULTS: The strongest baseline predictors of harmful alcohol use during follow-up were educational status, young adults, and high number of cigarettes smoked, present family history of alcoholism, treatment condition and number of drinks per episode of binge drinking. CONCLUSIONS: Binge drinkers are a heterogeneous group that responds to brief intervention or MA but in a subgroup of them these interventions fail to prevent harmful alcohol use. Other interventions should be implemented for these subjects. PMID- 26132299 TI - Exposure to tobacco, alcohol and drugs of abuse during pregnancy. A study of prevalence among pregnant women in Malaga (Spain). AB - The prevalence of substance abuse in women who become pregnant is similar to that of the general population, resulting in a high fetal exposure rate during the most vulnerable period regarding neurodevelopment and organogenesis. The present study was intended to assess the level of prenatal exposure to tobacco, alcohol or illicit drugs in the city of Malaga (Spain). It was designed as a cross sectional study, and based on the anonymous self-reports of participants. A total of 451 pregnant women were recruited in the first, second or third trimester. The prevalence in each of the quarters respectively was 21.2%, 18.5% and 13.3% for smoking, 40.7%, 23.1% and 17.1% for alcohol and 4.8%, 1.9% and 1.2% for cannabis. We also found that a higher educational level was associated with a lower consumption of tobacco (RR 0.659 [0.537-0.810] p<0.0001) and greater exposure to alcohol (RR 1.87 [1.30-2.69] p<0.0007). These results, particularly in regard to alcohol intake, are sufficiently alarming to alert obstetric care providers about the need to implement preventive measures. PMID- 26132300 TI - Motivational interviewing group at inpatient detoxification, its influence in maintaining abstinence and treatment retention after discharge. AB - The relapse rate after discharge from inpatient detoxification is high. The objective of this pilot study is to assess the sociodemographic, clinical and therapeutic factors associated with maintaining abstinence in patients who participated in a brief motivational interviewing group during admission for detoxification. A total of 46 patients, diagnosed substance dependent according to DSM -IV, and admitted to the Hospital Detoxification Unit, participated in a brief motivational interviewing group. Sociodemographic, clinical, motivation to change (University of Rhode Island Change Assessment, URICA) and satisfaction with the treatment group (Treatment Perceptions Questionnaire, CPT) data were collected. Abstinence and treatment retention two months after discharge were assessed by weekly telephone calls. A survival analysis was performed. Being male, having more cognitions of the maintenance stage of change at discharge, being satisfied with group therapy and therapist during hospitalization are associated with longer abstinence after discharge. The brief motivational interviewing group approach with patients admitted for detoxification is related to greater likelihood of maintaining abstinence and subsequent treatment retention. PMID- 26132301 TI - Predictors of weekly alcohol drinking and alcohol-related problems in binge drinking undergraduates. AB - The important implications generated by binge drinking among university students justify the interest to determine which factors predict its occurrence. Specifically, this study aims to assess the role of personality and drinking onset in predicting weekly alcohol consumption, and the impact of the whole set of variables in predicting the number of consequences associated with consumption in undergraduates. Two hundred and thirteen freshmen who were intensive consumers (binge drinkers) from the University Complutense of Madrid were evaluated. All of them filled in a self-registration of consumption, the BIS-11, the NEO-FFI and the IECI consequences associated with intake. The hierarchical regression analysis shows that the drinking onset appears to be a relevant predictor variable in explaining weekly consumption and the number of consequences. The same can be said of the weekly consumption variable with regard to the number of consequences. In general, the influence of personality is quite limited. It is interesting to point out that responsibility and impulsivity, along with age, explain most of the weekly consumption behavior among males. With respect to the consequences of consumption, only impulsivity and neuroticism contribute to explain them, but with less strength than age and weekly consumption. Our results justify the need to plan tighter interventions and consider new predictors that help to explain further weekly consumption in women. PMID- 26132302 TI - Epidemiology of Alcohol Abuse Among Spanish Immigrant Populations. AB - In recent years, the immigrant population has substantially increased in Spain. However, there is a lack of information in the knowledge of alcohol abuse among Spanish immigrants. We describe the epidemiology of alcohol abuse among foreign born immigrants versus Spanish natives. We carried out a cross-sectional study that uses data from the European Survey of Health on the General Population of Spain of 2009. A sample of 22,188 subjects was analyzed (of whom, 3,162 were foreign). Proxies of problematic alcohol consumption were the prevalence of excessive average consumption and the prevalence of excessive episodic consumption (binge drinking). Descriptive analysis of the population, determination of area of origin with major alcohol consumption and related factors for each kind of consumption, separating immigrant and native population, were performed. The immigrant profile was heterogeneous, though predominantly aged between 35 and 54, and were living with their family and working. 3.4% of immigrants and 3.2% of natives were considered excessive drinkers; 8.9% and 10%, respectively, reported binge drinking in the last year. Immigrants from Northern and Western Europe, and Latin America, Andean countries had significantly a higher report of frequent alcohol consumption and/or binge drinking compared to native. On the contrary, born in Africa was a protective factor. Unemployment was the most relevant related factor, being more important in the immigrant population. The excessive alcohol consumption in immigrants is dissimilar; the interventions must be adapted to their social situation, environments and areas of origin. PMID- 26132303 TI - Hepatitis C associated to substance abuse: ever closer to a treatment without Interferon. AB - With 3-4 million of new infections occurring annually, hepatitis C virus (HCV) infection is a global Public Health problem. In fact, hepatitis C virus infection is one of the leading causes of liver disease in the world; in Western countries, two thirds of the new HCV infections are associated with injection drug use. The treatment of hepatitis C will change in the coming years with the irruption of new anti-HCV drugs, the so called Direct Antiviral Agents (DAA) that attack key proteins of the HCV life cycle. The new antiviral drugs are effective, safer and better tolerated. The 2014 WHO HCV treatment guidelines include some of them. The new DAA are used in combination and it is expected that Interferon will be not necessary in future treatment regimens against HCV infection. The irruption of new and potent antivirals mandate the review of the current standards of care in the HCV infected population. More inclusive and proactive treatment policies will be necessary in those individuals with substance use disorders. PMID- 26132304 TI - Would Adding an Anesthesic to Nicotine Mouth Spray Increase Smoking Cessation Rates? Would this Justify Starting a Research Project? AB - Letter to the editor. PMID- 26132305 TI - Differentiation of Normal and Cancer Cell Adhesion on Custom Designed Protein Nanopatterns. AB - Cell adhesion to the extracellular matrix is deregulated in metastasis. However, traditional surfaces used to study cell adhesion do not faithfully mimic the in vivo microenvironment. Electron beam lithography (EBL) is able to generate customized protein nanopatterns. Here, we used an EBL-based green lithography approach to fabricate homogeneous and gradient, single (fibronectin, K-casein) and double (fibronectin, laminin) active component protein nanopatterns with micrometer scale spacing to investigate differences in adhesion of breast cancer cells (BCC) and normal mammary epithelial cells (NMEC). Our results showed that as expected, in contrast to NMEC, BCC were plastic: they tolerated nonadhesion promoting regions, adapted to flow and exploited gradients better. In addition, the number of focal adhesions but not their area appeared to be the dominant parameter for regulation of cell adhesion. Our findings also demonstrated that custom designed protein nanopatterns, which can properly mimic the in vivo microenvironment, enable realistic distinction of normal and cancerous cell adhesion. PMID- 26132306 TI - A randomized pilot study of dietary treatments for polycystic ovary syndrome in adolescents. AB - BACKGROUND: Evidence is lacking to recommend one diet over another when treating polycystic ovary syndrome (PCOS). OBJECTIVES: To obtain preliminary data, comparing the impact of a low-glycaemic load (LGL) vs. low-fat (LF) diet on biochemical hyperandrogenism in overweight and obese adolescents with PCOS. To ascertain feasibility of recruiting study participants, in partnership with an adolescent clinic, and implementing dietary interventions. METHODS: Randomized controlled trial of 19 overweight and obese adolescents with PCOS and not using hormonal contraceptives (HCs). Interventions comprised nutrition education, dietary counselling and cooking workshops to foster adherence to a LGL (45% carbohydrate, 35% fat, 20% protein) or LF (55% carbohydrate, 25% fat, 20% protein) diet over 6 months. Serum bioavailable testosterone was the primary outcome. RESULTS: Sixteen (LGL, n = 7; LF, n = 9) participants completed the study. Body fat percentage decreased (P < 0.05) in response to the interventions, with no difference between the LGL and LF groups (-1.2% vs. -2.2%; P = 0.16). Bioavailable testosterone did not change for either group (-0.4 vs. -1.8 ng dL( 1) ; P = 0.35). Regarding feasibility, recruiting adolescents posed a challenge, and use of HCs was a main reason for ineligibility. Participants attended 5.9 of 6 in-person visits and 2.6 of 3 cooking workshops, completed 4.9 of 6 telephone counselling calls, and reported high satisfaction with the diets and cooking workshops (>=8 on a 10-cm scale). CONCLUSIONS: Dietary interventions were beneficial for weight control but did not attenuate biochemical hyperandrogenism. Innovative strategies are needed to recruit adolescents for studies aimed at assessing independent effects of diet on features of PCOS. PMID- 26132307 TI - Tuberculosis Biomarker Extraction and Isothermal Amplification in an Integrated Diagnostic Device. AB - In this study, we integrated magnetic bead-based sample preparation and isothermal loop mediated amplification (LAMP) of TB in a single tube. Surrogate sputum samples produced by the Program for Appropriate Technology in Health containing inactivated TB bacteria were used to test the diagnostic. In order to test the sample preparation method, samples were lysed, and DNA was manually extracted and eluted into water in the tube. In a thermal cycler, LAMP amplified TB DNA from 103 TB cells/mL of sputum at 53.5 +/- 3.3 minutes, 104 cells/mL at 46.3 +/- 2.2 minutes, and 105 cells/mL at 41.6 +/- 1.9 minutes. Negative control samples did not amplify. Next, sample preparation was combined with in-tubing isothermal LAMP amplification by replacing the water elution chamber with a LAMP reaction chamber. In this intermediate configuration, LAMP amplified 103 cells/mL at 74 +/- 10 minutes, 104 cells/mL at 60 +/- 9 minutes, and 105 TB cells/mL of sputum at 54 +/- 9 minutes. Two of three negative controls did not amplify; one amplified at 100 minutes. In the semi-automated system, DNA was eluted directly into an isothermal reaction solution containing the faster OptiGene DNA polymerase. The low surrogate sputum concentration, 103 TB cells/mL, amplified at 52.8 +/- 3.3 minutes, 104 cells/mL at 45.4 +/- 11.3 minutes, and 105 cells/mL at 31.8 +/- 2.9 minutes. TB negative samples amplified at 66.4 +/- 7.4 minutes. This study demonstrated the feasibility of a single tube design for integrating sample preparation and isothermal amplification, which with further development could be useful for point-of-care applications, particularly in a low-resource setting. PMID- 26132309 TI - Automatic Clustering Using Multi-objective Particle Swarm and Simulated Annealing. AB - This paper puts forward a new automatic clustering algorithm based on Multi Objective Particle Swarm Optimization and Simulated Annealing, "MOPSOSA". The proposed algorithm is capable of automatic clustering which is appropriate for partitioning datasets to a suitable number of clusters. MOPSOSA combines the features of the multi-objective based particle swarm optimization (PSO) and the Multi-Objective Simulated Annealing (MOSA). Three cluster validity indices were optimized simultaneously to establish the suitable number of clusters and the appropriate clustering for a dataset. The first cluster validity index is centred on Euclidean distance, the second on the point symmetry distance, and the last cluster validity index is based on short distance. A number of algorithms have been compared with the MOPSOSA algorithm in resolving clustering problems by determining the actual number of clusters and optimal clustering. Computational experiments were carried out to study fourteen artificial and five real life datasets. PMID- 26132308 TI - Novel Role for p110beta PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells. AB - The organismal roles of the ubiquitously expressed class I PI3K isoform p110beta remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110beta, we document that full inactivation of p110beta leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110beta kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110beta results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110beta was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110beta also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110beta inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110beta inactivation. In line with a crucial role for p110beta in SCs, selective inactivation of p110beta in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110beta and AR have previously been reported to functionally interact. PMID- 26132310 TI - Determination of Geochemically Important Sterols and Triterpenols in Sediments Using Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry (UHPLC MS/MS). AB - A fast, sensitive, and selective ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method that is able to quantify geochemical biomarkers in sediment is described. A pool of 10 sterols, which can be used as biomarkers of autochthonous (cholesterol, cholestanol, brassicasterol, ergosterol), allochthonous (stigmasterol, beta-sitosterol, campesterol, and stigmastanol) and anthropogenic (coprostanol and epicoprostanol) organic matter (OM), and three triterpenols (lupeol, alpha-amyrin, and beta-amyrin) were chosen as the analytes. The method showed excellent analytical parameters, and, compared with the traditional GC-MS methods that are commonly applied for the analysis of sterols, this method requires no sample cleanup or derivatization and presents improved values for the LOD and LOQ. UHPLC can separate the diastereoisomers (epicoprostanol, coprostanol, and cholestanol) and the isomers (lupeol, alpha amyrin, and beta-amyrin). The method was successfully applied for the quantification of the biomarkers, and thus, it was applied to assess the OM sources and the impacts of anthropogenic activities in sediments from different environments, such as Antarctica and other Brazilian systems (Continental Shelf, Sao Sebastiao Channel, and Santos Estuary). Unique profiles of the biomarkers were observed for the contrasting environments, and beta-amyrin and cholesterol were more predominant in the Santos Estuary and Antarctica samples, respectively. The sterol ratios indicated a higher level of sewage contamination in the Santos Estuary. PMID- 26132311 TI - Removal of Trace Elements by Cupric Oxide Nanoparticles from Uranium In Situ Recovery Bleed Water and Its Effect on Cell Viability. AB - In situ recovery (ISR) is the predominant method of uranium extraction in the United States. During ISR, uranium is leached from an ore body and extracted through ion exchange. The resultant production bleed water (PBW) contains contaminants such as arsenic and other heavy metals. Samples of PBW from an active ISR uranium facility were treated with cupric oxide nanoparticles (CuO NPs). CuO-NP treatment of PBW reduced priority contaminants, including arsenic, selenium, uranium, and vanadium. Untreated and CuO-NP treated PBW was used as the liquid component of the cell growth media and changes in viability were determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in human embryonic kidney (HEK 293) and human hepatocellular carcinoma (Hep G2) cells. CuO-NP treatment was associated with improved HEK and HEP cell viability. Limitations of this method include dilution of the PBW by growth media components and during osmolality adjustment as well as necessary pH adjustment. This method is limited in its wider context due to dilution effects and changes in the pH of the PBW which is traditionally slightly acidic however; this method could have a broader use assessing CuO-NP treatment in more neutral waters. PMID- 26132312 TI - Intranasal spray medications for maintenance therapy of allergic rhinitis. AB - BACKGROUND: Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR) by providing direct delivery of medication to the nasal mucosa, reducing the potential for systemic adverse effects, decreasing burden of disease, and improving quality of life. OBJECTIVE: To review currently available intranasal sprays indicated for maintenance therapy of AR in the United States: intranasal antihistamines (INAH); intranasal corticosteroids (INCS); and MP AzeFlu, a single formulation nasal spray of the INAH, azelastine hydrochloride, and the INCS, fluticasone propionate. METHODS: MEDLINE searches were conducted to identify placebo-controlled studies of commercially available prescription nasal sprays at U.S.-approved doses and indications, and published after an earlier systematic review of AR treatment. Inclusion criteria were >=20 subjects; duration of >=2 weeks for seasonal (or episodic) AR, >=4 weeks for perennial (or persistent) AR, and reporting a total nasal symptom score as a primary or secondary outcome. RESULTS: Twenty studies met the inclusion criteria: 4 pediatric, 16 adult/adolescent. There were 4 perennial AR studies (381 children, 1607 adults) and 16 seasonal AR trials (3081 children, 6548 adults). In these studies, 2451 subjects (481 children, 1970 adults) received an INCS, 3001 (1116 children, 1885 adults) received an INAH, and 346 adult subjects received MP AzeFlu. All active treatments were well tolerated and effective as measured by the reduction in nasal symptoms. Head-to-head comparisons were only available for MP-AzeFlu versus the individual active agent components. MP-AzeFlu provided significantly greater symptom relief than either azelastine or fluticasone propionate alone and with an onset starting at 30 minutes after the dose. CONCLUSION: The most recent addition to intranasal sprays for the maintenance therapy of AR is MP-AzeFlu, a single formulation nasal spray of azelastine hydrochloride and fluticasone propionate in an advanced delivery system. Analysis of clinical data showed this to be the first new intranasal medication that provides greater clinical benefit than an INCS in treating AR. PMID- 26132313 TI - No reduced risk of overall, colorectal, lung, breast, and prostate cancer with metformin therapy in diabetic patients: database analyses from Germany and the UK. AB - BACKGROUND: In observational studies, a lower cancer risk was reported for patients with diabetes using metformin. However, many of these studies had shortcomings like time-related biases. We aimed to compare the incidence rate of any cancer and some selected cancer sites in metformin, sulfonylurea, and insulin users and to reduce some major biases common in observational studies. METHODS: In a retrospective database study, we used patient data from general practices throughout Germany and the UK. Eighty thousand two hundred and sixty-three patients aged 30-89 years at diagnosis of diabetes were observed for a mean follow-up of 4.8 years after the first antidiabetes medication. In Cox regression models adjusted for age, sex, country, metabolic factors, diabetes duration, medication, and comorbidity, patients who started using metformin were compared with those who started using sulfonylurea (or insulin) (intention-to-treat type analysis), and, additionally, patients with metformin monotherapy were compared with those with sulfonylurea (or insulin) monotherapy. The initial 12 months of follow-up after the first antidiabetes prescription were excluded. RESULTS: Four thousand seven hundred seventy-nine (6.0%) incident cases of cancer were identified. Throughout all analyses, hazard ratios were close to the null for comparisons of metformin use with sulfonylurea and insulin use. For example, in intention-to-treat analyses comparing metformin with sulfonylurea use, hazard ratios were 1.05 (95%CI: 0.99-1.12) for any cancer, 1.05 (0.85-1.30) for colorectal, 1.04 (0.82-1.31) for lung, 1.03 (0.81-1.30) for breast, and 0.89 (0.73-1.08) for prostate cancer. CONCLUSION: This study provides evidence that metformin has no protective effect on the incidence of cancer in persons with diabetes. PMID- 26132314 TI - B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment. AB - BACKGROUND: Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS. METHODS: In this single-center, open-label, one-armed phase II study (NCT01156909), 29 patients were included for treatment with rituximab (500 mg/m2) two infusions two weeks apart, followed by maintenance rituximab infusions after 3, 6, 10 and 15 months, and with follow-up for 36 months. FINDINGS: Major or moderate responses, predefined as lasting improvements in self-reported Fatigue score, were detected in 18 out of 29 patients (intention to treat). Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. At end of follow-up (36 months), 11 out of 18 responding patients were still in ongoing clinical remission. For major responders, the mean lag time from first rituximab infusion until start of clinical response was 23 weeks (range 8-66). Among the nine patients from the placebo group in the previous randomized study with no significant improvement during 12 months follow-up after saline infusions, six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study. Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight patients experienced one or more transient symptom flares after rituximab infusions. There was no unexpected toxicity. CONCLUSION: In a subgroup of ME/CFS patients, prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses. The observed patterns of delayed responses and relapse after B-cell depletion and regeneration, a three times higher disease prevalence in women than in men, and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS may be a variant of an autoimmune disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01156909. PMID- 26132315 TI - Five-year results of a randomized clinical trial of conventional surgery, endovenous laser ablation and ultrasound-guided foam sclerotherapy in patients with great saphenous varicose veins. AB - BACKGROUND: A variety of techniques exist for the treatment of patients with great saphenous vein (GSV) varicosities. Few data exist on the long-term outcomes of these interventions. METHODS: Patients undergoing conventional surgery, endovenous laser ablation (EVLA) and ultrasound-guided foam sclerotherapy (UGFS) for GSV varicose veins were followed up for 5 years. Primary outcome was obliteration or absence of the treated GSV segment; secondary outcomes were absence of GSV reflux, and change in Chronic Venous Insufficiency quality-of-life Questionnaire (CIVIQ) and EuroQol - 5D (EQ-5DTM) scores. RESULTS: A total of 224 legs were included (69 conventional surgery, 78 EVLA, 77 UGFS), 193 (86.2 per cent) of which were evaluated at final follow-up. At 5 years, Kaplan-Meier estimates of obliteration or absence of the GSV were 85 (95 per cent c.i. 75 to 92), 77 (66 to 86) and 23 (14 to 33) per cent in the conventional surgery, EVLA and UGFS groups respectively. Absence of above-knee GSV reflux was found in 85 (73 to 92), 82 (72 to 90) and 41 (30 to 53) per cent respectively. CIVIQ scores deteriorated over time in patients in the UGFS group (0.98 increase per year, 95 per cent c.i. 0.16 to 1.79), and were significantly worse than those in the EVLA group (-0.44 decrease per year, 95 per cent c.i. -1.22 to 0.35) (P = 0.013). CIVIQ scores for the conventional surgery group did not differ from those in the EVLA and UGFS groups (0.44 increase per year, 95 per cent c.i. -0.41 to 1.29). EQ 5DTM scores improved equally in all groups. CONCLUSION: EVLA and conventional surgery were more effective than UGFS in obliterating the GSV 5 years after intervention. UGFS was associated with substantial rates of GSV reflux and inferior CIVIQ scores compared with EVLA and conventional surgery. REGISTRATION NUMBER: NCT00529672 (http://www.clinicaltrials.gov). PMID- 26132316 TI - High-Fat, High-Calorie Diet Enhances Mammary Carcinogenesis and Local Inflammation in MMTV-PyMT Mouse Model of Breast Cancer. AB - Epidemiological studies provide strong evidence that obesity and the associated adipose tissue inflammation are risk factors for breast cancer; however, the molecular mechanisms are poorly understood. We evaluated the effect of a high fat/high-calorie diet on mammary carcinogenesis in the immunocompetent MMTV-PyMT murine model. Four-week old female mice (20/group) were randomized to receive either a high-fat (HF; 60% kcal as fat) or a low-fat (LF; 16% kcal) diet for eight weeks. Body weights were determined, and tumor volumes measured by ultrasound, each week. At necropsy, the tumors and abdominal visceral fat were weighed and plasma collected. The primary mammary tumors, adjacent mammary fat, and lungs were preserved for histological and immunohistochemical examination and quantification of infiltrating macrophages, crown-like structure (CLS) formation, and microvessel density. The body weight gains, visceral fat weights, the primary mammary tumor growth rates and terminal weights, were all significantly greater in the HF-fed mice. Adipose tissue inflammation in the HF group was indicated by hepatic steatosis, pronounced macrophage infiltration and CLS formation, and elevations in plasma monocyte chemoattractant protein-1 (MCP-1), leptin and proinflammatory cytokine concentrations. HF intake was also associated with higher tumor-associated microvascular density and the proangiogenic factor MCP-1. This study provides preclinical evidence in a spontaneous model of breast cancer that mammary adipose tissue inflammation induced by diet, enhances the recruitment of macrophages and increases tumor vascular density suggesting a role for obesity in creating a microenvironment favorable for angiogenesis in the progression of breast cancer. PMID- 26132317 TI - Tumour Movement in Proton Therapy: Solutions and Remaining Questions: A Review. AB - Movement of tumours, mostly by respiration, has been a major problem for treating lung cancer, liver tumours and other locations in the abdomen and thorax. Organ motion is indeed one component of geometrical uncertainties that includes delineation and target definition uncertainties, microscopic disease and setup errors. At present, minimising motion seems to be the easiest to implement in clinical practice. If combined with adaptive approaches to correct for gradual anatomical variations, it may be a practical strategy. Other approaches such as repainting and tracking could increase the accuracy of proton therapy delivery, but advanced 4D solutions are needed. Moreover, there is a need to perform clinical studies to investigate which approach is the best in a given clinical situation. The good news is that existing and emerging technology and treatment planning systems as will without doubt lead in the forthcoming future to practical solutions to tackle intra-fraction motion in proton therapy. These developments may also improve motion management in photon therapy as well. PMID- 26132320 TI - General Practitioner Preferences in Managing Care of Multiple Sclerosis Patients. AB - BACKGROUND: Multiple sclerosis (MS) is a lifelong neurological disorder requiring care in a variety of settings. The purpose of this study is to describe preferences of general practitioners (GPs) with regards to providing care for MS patients. METHODS: A stratified sample of 900 GPs in the province of Quebec were sent a questionnaire, with 266 returning completed questionnaires. Respondents were surveyed about their preferences using four clinical scenarios describing hypothetical patients experiencing different stages of MS. Respondents were asked whether they would continue managing the patient themselves, formally refer the patient to a specialist, or seek specialist advice. RESULTS: In two scenarios representing stable courses, 40.9% and 61.6% of GPs, respectively, intended to manage the patient themselves. GPs who reported having experience with MS patients were more likely to report an intention to continue management. In one scenario, GPs operating in rural areas were less likely to consider management than those in the Montreal metropolitan area (odds ratio=0.422, 95% confidence interval 0.20-0.90). CONCLUSIONS: For MS patients with a stable disease course, an important proportion of GPs appear to be willing to manage long-term care for MS patients. PMID- 26132328 TI - Electrically switchable polymer stabilised broadband infrared reflectors and their potential as smart windows for energy saving in buildings. AB - Electrically switchable broadband infrared reflectors that are relatively transparent in the visible region have been fabricated using polymer stabilised cholesteric liquid crystals. The IR reflectors can change their reflection/transmission properties by applying a voltage in response to changes in environmental conditions. Simulations predict that a significant amount of energy can be saved on heating, cooling and lighting of buildings in places such as Madrid by using this switchable IR reflector. We have also fabricated a switchable IR reflector which can also generate electricity. These polymer based switchable IR reflectors are of high potential as windows of automobiles and buildings to control interior temperatures and save energy. PMID- 26132327 TI - Lethal and Sublethal Effects of Insecticides Used on Citrus, on the Ectoparasitoid Tamarixia radiata. AB - Huanglongbing (HLB) is a disease associated with the bacteria "Candidatus Liberibacter spp." and has been devastating citrus orchards around the world. Its management involves control of the insect vector, the Asian citrus psyllid Diaphorina citri Kuwayama. However, the indiscriminate use of chemicals has caused pest outbreaks and eliminated the natural enemies of the vector, such as the parasitoid Tamarixia radiata (Waterston), the main agent for biological control of D. citri. This study assessed the lethal and sublethal effects of insecticides recommended for integrated production of citrus on the parasitoid T. radiata. When adult parasitoids were exposed to residues of 25 insecticides, 20% of them, i.e., gamma-cyhalothrin, etofenprox, azadirachtin, tebufenozide and pyriproxyfen, were considered as harmless (Class 1), 12% as slightly harmful (Class 2), 12% as moderately harmful (Class 3) and 56% as harmful (Class 4), according to the classification proposed by the IOBC/WPRS. Afterward, 14 insecticides (5 harmless and 9 harmful) were sprayed on the parasitoid pupae. Of the 14 insecticides tested, only the organophosphates dimethoate and chlorpyrifos affected the parasitoid emergence. The effects of insecticides on the parasitism capacity of adults exposed to residues of azadirachtin, etofenprox, gamma cyhalothrin, pyriproxyfen and tebufenozide (harmless) were also evaluated. Tebufenozide and gamma-cyhalothrin affected the parasitism of the F0 generation, but did not affect the emergence of the F1 and F2 generations. Therefore, for an effective IPM program, selective insecticides or harmful pesticides to adult parasitoids could be used in the field, provided that the adults do not occur naturally and the chemical applications do not coincide with parasitoid releases. PMID- 26132329 TI - Use of Anthropogenic Sea Floor Structures by Australian Fur Seals: Potential Positive Ecological Impacts of Marine Industrial Development? AB - Human-induced changes to habitats can have deleterious effects on many species that occupy them. However, some species can adapt and even benefit from such modifications. Artificial reefs have long been used to provide habitat for invertebrate communities and promote local fish populations. With the increasing demand for energy resources within ocean systems, there has been an expansion of infrastructure in near-shore benthic environments which function as de facto artificial reefs. Little is known of their use by marine mammals. In this study, the influence of anthropogenic sea floor structures (pipelines, cable routes, wells and shipwrecks) on the foraging locations of 36 adult female Australian fur seals (Arctocephalus pusillus doriferus) was investigated. For 9 (25%) of the individuals, distance to anthropogenic sea floor structures was the most important factor in determining the location of intensive foraging activity. Whereas the influence of anthropogenic sea floor structures on foraging locations was not related to age and mass, it was positively related to flipper length/standard length (a factor which can affect manoeuvrability). A total of 26 (72%) individuals tracked with GPS were recorded spending time in the vicinity of structures (from <1% to >75% of the foraging trip duration) with pipelines and cable routes being the most frequented. No relationships were found between the amount of time spent frequenting anthropogenic structures and individual characteristics. More than a third (35%) of animals foraging near anthropogenic sea floor structures visited more than one type of structure. These results further highlight potentially beneficial ecological outcomes of marine industrial development. PMID- 26132330 TI - Painful Muscle Cramps Possibly Associated with Withdrawal from Methylphenidate. PMID- 26132331 TI - Effects of Prolactin and Lactation on A15 Dopamine Neurones in the Rostral Preoptic Area of Female Mice. AB - There are several distinct populations of dopamine neurones in the hypothalamus. Some of these, such as the A12 tuberoinfundibular dopamine neurones and the A14 periventricular dopamine neurones, are known to be regulated by the anterior pituitary hormone prolactin, whereas others, such as the A13 zona incerta dopaminergic neurones, are not. The present study aimed to investigate the role of prolactin in the regulation of a fourth population of hypothalamic dopamine neurones: the A15 dopamine population in the rostral hypothalamus. These neurones may play a role in the regulation of gonadotrophin-releasing hormone (GnRH) secretion, and we hypothesised that they might contribute to the suppression of GnRH release and infertility caused by hyperprolactinaemia. Under basal (low prolactin) conditions, only 8% of A15 dopamine neurones in the anteroventral periventricular nucleus (AVPV) of vehicle-treated dioestrous mice expressed phosphorylated signal transducer and activator of transcription 5 (pSTAT5), as labelled by immunohistochemistry. We have previously shown that this transcription factor can be used as an index of prolactin-receptor activation. Following acute prolactin administration, 35% of AVPV dopamine neurones co expressed pSTAT5, whereas, during lactation, when endogenous prolactin levels are chronically elevated, 55% of AVPV dopamine neurones expressed pSTAT5. There was also a significant increase in dopamine turnover in the rostral hypothalamus, both in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis and in the rostral preoptic area during lactation, with the 3,4 dihydroxyphenylacetic acid/dopamine ratio increasing from 0.28 +/- 0.04 and 0.14 +/- 0.01 in dioestrous mice to 0.82 +/- 0.06 and 0.38 +/- 0.03, respectively, in day 7 lactating mice. It is not yet known whether this change is driven by the hyperprolactinaemia of lactation, or another lactation-specific signal. These data demonstrate that the A15 dopaminergic neurones of the rostral hypothalamus are responsive to exogenous prolactin and may be regulated by endogenous prolactin during lactation. PMID- 26132332 TI - Contribution of Aggregate States and Energetic Disorder to a Squaraine System Targeted for Organic Photovoltaic Devices. AB - Squaraine dyes have significant potential for use in organic photovoltaic devices because their chemical and packing structure tunability leads to a broad solid state panchromaticity. Nevertheless, broadening of the spectrum does not always give rise to increasing power conversion efficiencies. Furthermore, the same processing strategy used to make devices from different squaraines does not lead to the same optimized performance. In this work, by varying the environmental conditions of a set of anilinic squaraines, we demonstrate that spin-cast thin films are made up of a complex set of states, with each state contributing differently to the overall device efficiency. We demonstrate crystallochromy in that small changes in the packing structure give rise to dramatically different absorption spectra. Through a remarkable comparison between squaraines in poly(methyl methacrylate) solid solution and squaraine:PC60BM blends, we also show long-range and orientational disorder broadening, which distorts the ability to correlate qualitative spectroscopic assessment with an understanding of the device mechanism. We conclude that a full quantitative assessment of the populations of each excited state must be carried out in order to make progress toward an improved understanding of each state's contribution to charge transfer at the bulk heterojunction interface. PMID- 26132333 TI - Structure and Function of Cu(I)- and Zn(II)-ATPases. AB - Copper and zinc are micronutrients essential for the function of many enzymes while also being toxic at elevated concentrations. Cu(I)- and Zn(II)-transporting P-type ATPases of subclass 1B are of key importance for the homeostasis of these transition metals, allowing ion transport across cellular membranes at the expense of ATP. Recent biochemical studies and crystal structures have significantly improved our understanding of the transport mechanisms of these proteins, but many details about their structure and function remain elusive. Here we compare the Cu(I)- and Zn(II)-ATPases, scrutinizing the molecular differences that allow transport of these two distinct metal types, and discuss possible future directions of research in the field. PMID- 26132334 TI - Transparent conductive oxide-free perovskite solar cells with PEDOT:PSS as transparent electrode. AB - Perovskite solar cells (PSCs) have been attracting considerable attention because of their low fabrication cost and impressive energy conversion efficiency. Most PSCs are built on transparent conductive oxides (TCOs) such as fluorine-doped tin oxide (FTO) or indium tin oxide (ITO), which are costly and rigid. Therefore, it is significant to explore alternative materials as the transparent electrode of PSCs. In this study, highly conductive and highly transparent poly(3,4 ethylenedioxythiophene):polystyrenesulfonate ( PEDOT: PSS) films were investigated as the transparent electrode of both rigid and flexible PSCs. The conductivity of PEDOT: PSS films on rigid glass or flexible poly(ethylene terephthalate) (PET) substrate is significantly enhanced through a treatment with methanesulfonic acid (MSA). The optimal power conversion efficiency (PCE) is close to 11% for the rigid PSCs with an MSA-treated PEDOT: PSS film as the transparent electrode on glass, and it is more than 8% for the flexible PSCs with a MSA-treated PEDOT: PSS film as the transparent electrode on PET. The flexible PSCs exhibit excellent mechanical flexibility in the bending test. PMID- 26132335 TI - Mononuclear and Terminally Bound Titanium Nitrides. AB - The Ti(III) azido complex (PN)2Ti(N3) (PN(-) = (N-(2-(diisopropylphosphino)-4 methylphenyl)-2,4,6-trimethylanilide), can be reduced with KC8 to afford the nitride salt [MU2-K(OEt2)]2[(PN)2Ti=N]2 in excellent yield. While treatment of the dimer with 18-crown-6 yields a mononuclear nitride, complete encapsulation of the alkali metal with cryptand provides the terminally bound nitride as a discrete salt [K(2,2,2-Kryptofix)][(PN)2Ti=N]. All complexes reported here have been structurally confirmed and also spectroscopically, and the Ti-Nnitride bonding has been probed theoretically via DFT-based methods. PMID- 26132336 TI - Postoperative Expansion is not a Primary Cause of Infection in Immediate Breast Reconstruction with Tissue Expanders. AB - Perioperative infection is the most common and dreaded complication associated with tissue expander (TE) breast reconstruction. Historically, the expansion period was thought to be the time of greatest hazard to the implant. However, recent institutional observations suggest infectious complications occur prior to expansion. This investigation, therefore, was conducted to determine the timing of infectious complications associated with two-stage TE breast reconstructions. Following IRB approval, a retrospective review of all consecutive two-stage immediate TE breast reconstructions at a single institution from November 2007 to November 2011 was conducted. Reconstructions were then divided into two cohorts: those suffering infectious complications and those that did not. Infectious complications including minor cellulitis, major cellulitis, abscess drainage, and explantation were identified. Various operative and patient variables were evaluated in comparison. Eight hundred ninety immediate two-stage TE breast reconstructions met inclusion criteria. Patients suffering infection were older (55.4 years versus 49.3 years; p < 0.001), and more likely to have therapeutic mastectomy (94% versus 61%; p < 0.0001), the use of acellular dermal matrix (ADM; 72.5% versus 54.9%; p = 0.001), and greater initial TE fill (448.6 mL versus 404.7 mL; p = 0.0078). The average time to developing of infectious symptoms was 29.6 days (range 9-142 days), with 94.6% (n = 87) of infections prior to the start of expansion. Perioperative infections in immediate two-stage TE to implant breast reconstructions are significant and occur mostly prior to the start of expansion. Thus, challenging the conventional wisdom that instrumentation during expander filling as the primary cause of implant infections. Possible etiologic factors include greater age, therapeutic mastectomy versus prophylactic mastectomy, larger initial TE fill, and the use of ADM. PMID- 26132337 TI - Fungal serotype-specific differences in bacterial-yeast interactions. AB - Cryptococcus neoformans (Cn) causes meningoencephalitis in immunocompromised individuals. This encapsulated fungus can be found interacting with environmental microbes in soil contaminated with pigeon excrement. Cn survival within polymicrobial and other challenging communities has been shown to affect the evolution of its virulence factors. We compared the survival of 10 serotype A and D strains after interaction with the soil bacterium, Acinetobacter baumannii (Ab). Although co-incubation with Ab stimulated virulence factors production by strains of both cryptococcal serotypes, on average, serotype A strains displayed significantly higher survival rate, number of metabolically active cells within biofilms, and capsular polysaccharide production and release than serotype D strains. Our findings suggest that interactions of Cn with other microorganisms influence the fungus' regulation and production of virulence factors, important elements needed for the successful colonization of the human host. PMID- 26132338 TI - Multifocal capillary malformations in an older, asymptomatic child with a novel RASA1 mutation. AB - Multifocal capillary malformation (CM) is the cardinal feature of patients with RASA1 mutations. These CMs are 'red flags', signalling the possible association with an arteriovenous malformation (AVM) or an arteriovenous fistula (AVF). We report an 8-year-old boy who presented with > 20 CMs, who was found to have a novel mutation in the RASA1 gene. Radiological screening of children with RASA1 mutations is not standardized, and we elected to carry out baseline magnetic resonance imaging of the brain and spine in our case, which gave normal results. We discuss the recent literature and our approach in the management of such a case. PMID- 26132339 TI - The Serine Protease EspC from Enteropathogenic Escherichia coli Regulates Pore Formation and Cytotoxicity Mediated by the Type III Secretion System. AB - Type III secretion systems (T3SSs) are specialized macromolecular machines critical for bacterial virulence, and allowing the injection of bacterial effectors into host cells. The T3SS-dependent injection process requires the prior insertion of a protein complex, the translocon, into host cell membranes consisting of two-T3SS hydrophobic proteins, associated with pore-forming activity. In all described T3SS to date, a hydrophilic protein connects one hydrophobic component to the T3SS needle, presumably insuring the continuum between the hollow needle and the translocon. In the case of Enteropathogenic Escherichia coli (EPEC), the hydrophilic component EspA polymerizes into a filament connecting the T3SS needle to the translocon composed of the EspB and EspD hydrophobic proteins. Here, we identify EspA and EspD as targets of EspC, a serine protease autotransporter of Enterobacteriaceae (SPATE). We found that in vitro, EspC preferentially targets EspA associated with EspD, but was less efficient at proteolyzing EspA alone. Consistently, we found that EspC did not regulate EspA filaments at the surface of primed bacteria that was devoid of EspD, but controlled the levels of EspD and EspA secreted in vitro or upon cell contact. While still proficient for T3SS-mediated injection of bacterial effectors and cytoskeletal reorganization, an espC mutant showed increased levels of cell-associated EspA and EspD, as well as increased pore formation activity associated with cytotoxicity. EspP from enterohaemorrhagic E. coli (EHEC) also targeted translocator components and its activity was interchangeable with that of EspC, suggesting a common and important function of these SPATEs. These findings reveal a novel regulatory mechanism of T3SS-mediated pore formation and cytotoxicity control during EPEC/EHEC infection. PMID- 26132340 TI - Localised corrosion: general discussion. PMID- 26132342 TI - Extrahepatic comorbidities associated with hepatitis C virus in HIV-infected patients. AB - PURPOSE OF REVIEW: HIV infection facilitates progression of hepatitis C virus (HCV)-related liver fibrosis, thus increasing the risk of cirrhosis and decompensated liver disease. Although the primary target of HCV infection is the liver, extrahepatic manifestations related to HCV contribute significantly to morbidity and mortality in patients with chronic hepatitis C. We review current data on extrahepatic comorbidities associated with HCV in HIV-infected patients. RECENT FINDINGS: A large proportion of individuals coinfected with HIV/HCV has extrahepatic manifestations that may be indirectly or directly related to HCV infection. Extrahepatic manifestations include autoimmune and/or lymphoproliferative disorders, and cardiovascular, renal, metabolic, and central nervous system manifestations. Chronic immune activation and systemic inflammation, hallmarks of both HIV and HCV infection, may contribute greatly to extrahepatic comorbidities of HCV in this population group. There is substantial evidence that successful antiviral therapy might reduce both hepatic and extrahepatic manifestations of HCV infection in patients coinfected with HIV/HCV. SUMMARY: A substantial burden of the morbidity and the mortality related to HCV in patients with or without HIV infection depends on its extrahepatic manifestations. HCV eradication following successful antiviral therapy might reduce both. PMID- 26132343 TI - Assessing liver disease in HIV-HCV coinfected patients. AB - PURPOSE OF REVIEW: It is estimated that up to 10% of patients with HIV have chronic hepatitis C (HCV)-HIV coinfection in the Western world. Assessment of liver disease is essential in such patients in order to diagnose cirrhosis at an early stage, prioritize for anti-HCV treatment but also assess fibrosis regression after sustained viral response (SVR). In this review, we present a critical appraisal of liver disease assessment in patients with HIV-HCV co infection. RECENT FINDINGS: Liver biopsy has largely been replaced by noninvasive fibrosis assessment in most coinfected patients, although it is still of value if there are concerns of additional diagnoses. Noninvasive assessment includes serum markers and liver stiffness measurement using elastography-based techniques. Certain serum markers, such as FIB-4, SHASTA index, and Fibrometer HIVC have been specifically developed in patients with HIV-HCV coinfection. Transient elastography has advantages over serum markers, as it is not influenced by concomitant antiretroviral medication, HIV replication, CD4 cell count, or nonliver inflammatory processes. SUMMARY: Noninvasive markers are increasingly used for clinical decision-making and predicting clinical outcomes in HIV-HCV coinfected patients. The concept of residual risk for liver-related events after SVR needs to be further explored with noninvasive fibrosis tools in prospective studies. PMID- 26132341 TI - Establishment and Characterization of UTI and CAUTI in a Mouse Model. AB - Urinary tract infections (UTI) are highly prevalent, a significant cause of morbidity and are increasingly resistant to treatment with antibiotics. Females are disproportionately afflicted by UTI: 50% of all women will have a UTI in their lifetime. Additionally, 20-40% of these women who have an initial UTI will suffer a recurrence with some suffering frequent recurrences with serious deterioration in the quality of life, pain and discomfort, disruption of daily activities, increased healthcare costs, and few treatment options other than long term antibiotic prophylaxis. Uropathogenic Escherichia coli (UPEC) is the primary causative agent of community acquired UTI. Catheter-associated UTI (CAUTI) is the most common hospital acquired infection accounting for a million occurrences in the US annually and dramatic healthcare costs. While UPEC is also the primary cause of CAUTI, other causative agents are of increased significance including Enterococcus faecalis. Here we utilize two well-established mouse models that recapitulate many of the clinical characteristics of these human diseases. For UTI, a C3H/HeN model recapitulates many of the features of UPEC virulence observed in humans including host responses, IBC formation and filamentation. For CAUTI, a model using C57BL/6 mice, which retain catheter bladder implants, has been shown to be susceptible to E. faecalis bladder infection. These representative models are being used to gain striking new insights into the pathogenesis of UTI disease, which is leading to the development of novel therapeutics and management or prevention strategies. PMID- 26132344 TI - Combining UHPLC-High Resolution MS and Feeding of Stable Isotope Labeled Polyketide Intermediates for Linking Precursors to End Products. AB - We present the results from stable isotope labeled precursor feeding studies combined with ultrahigh performance liquid chromatography-high resolution mass spectrometry for the identification of labeled polyketide (PK) end-products. Feeding experiments were performed with (13)C8-6-methylsalicylic acid (6-MSA) and (13)C14-YWA1, both produced in-house, as well as commercial (13)C7-benzoic acid and (2)H7-cinnamic acid, in species of Fusarium, Byssochlamys, Aspergillus, and Penicillium. Incorporation of 6-MSA into terreic acid or patulin was not observed in any of six evaluated species covering three genera, because the 6-MSA was shunted into (2Z,4E)-2-methyl-2,4-hexadienedioic acid. This indicates that patulin and terreic acid may be produced in a closed compartment of the cell and that (2Z,4E)-2-methyl-2,4-hexadienedioic acid is a detoxification product toward terreic acid and patulin. In Fusarium spp., YWA1 was shown to be incorporated into aurofusarin, rubrofusarin, and antibiotic Y. In A. niger, benzoic acid was shown to be incorporated into asperrubrol. Incorporation levels of 0.7-20% into the end-products were detected in wild-type strains. Thus, stable isotope labeling is a promising technique for investigation of polyketide biosynthesis and possible compartmentalization of toxic metabolites. PMID- 26132345 TI - Ionization Mechanism of Matrix-Assisted Laser Desorption/Ionization. AB - In past studies, mistakes in determining the ionization mechanism in matrix assisted laser desorption/ionization (MALDI) were made because an inappropriate ion-to-neutral ratio was used. The ion-to-neutral ratio of the analyte differs substantially from that of the matrix in MALDI. However, these ratios were not carefully distinguished in previous studies. We begin by describing the properties of ion-to-neutral ratios and reviews early experimental measurements. A discussion of the errors committed in previous theoretical studies and a comparison of recent experimental measurements follow. We then describe a thermal proton transfer model and demonstrate how the model appropriately describes ion to-neutral ratios and the total ion intensity. Arguments raised to challenge thermal ionization are then discussed. We demonstrate how none of the arguments are valid before concluding that thermal proton transfer must play a crucial role in the ionization process of MALDI. PMID- 26132346 TI - Sensor Array Design for Complex Sensing Tasks. AB - Chemical detection in complex environments presents numerous challenges for successful implementation. Arrays of sensors are often implemented for complex chemical sensing tasks, but systematic understanding of how individual sensor response characteristics contribute overall detection system performance remains elusive, with generalized strategies for design and optimization of these arrays rarely reported and even less commonly adopted by practitioners. This review focuses on the literature of nonspecific sensor array design and optimization strategies as well as related work that may inform future efforts in complex sensing with arrays. PMID- 26132347 TI - Single-Molecule Investigations of Morphology and Mass Transport Dynamics in Nanostructured Materials. AB - Nanostructured materials such as mesoporous metal oxides and phase-separated block copolymers form the basis for new monolith, membrane, and thin film technologies having applications in energy storage, chemical catalysis, and separations. Mass transport plays an integral role in governing the application specific performance characteristics of many such materials. The majority of methods employed in their characterization provide only ensemble data, often masking the nanoscale, molecular-level details of materials morphology and mass transport. Single-molecule fluorescence methods offer direct routes to probing these characteristics on a single-molecule/single-nanostructure basis. This article provides a review of single-molecule studies focused on measurements of anisotropic diffusion, adsorption, partitioning, and confinement in nanostructured materials. Experimental methods covered include confocal and wide field fluorescence microscopy. The results obtained promise to deepen our understanding of mass transport mechanisms in nanostructures, thus aiding in the realization of advanced materials systems. PMID- 26132348 TI - Synthetic Nano- and Micromachines in Analytical Chemistry: Sensing, Migration, Capture, Delivery, and Separation. AB - Synthetic nano- and microscale machines move autonomously in solution or drive fluid flows by converting sources of energy into mechanical work. Their sizes are comparable to analytes (sub-nano- to microscale), and they respond to signals from each other and their surroundings, leading to emergent collective behavior. These machines can potentially enable hitherto difficult analytical applications. In this article, we review the development of different classes of synthetic nano and micromotors and pumps and indicate their possible applications in real-time in situ chemical sensing, on-demand directional transport, cargo capture and delivery, as well as analyte isolation and separation. PMID- 26132349 TI - Patterns in Wheeled Mobility Skills Training, Equipment Evaluation, and Utilization: Findings from the SCIRehab Project. AB - Patients with traumatic spinal cord injury (SCI) participate in manual and power wheelchair (WC) skills training during inpatient rehabilitation; wheeled mobility evaluations aim to optimize use, fit, and function of equipment following discharge. Occupational and physical therapists documented treatment sessions during inpatient rehabilitation to describe types and quantity of WC skills training and adaptive equipment (AE) provided by neurological level of injury. Most patients participated in WC skills training; variation in type and frequency exists. Propulsion/driving skills were practiced most frequently. A majority of patients participated in equipment evaluations; assessment/prescription and fitting were performed frequently; mat evaluations were done infrequently. Most patients received mobility equipment in a timely manner; they continued to use their WC and were satisfied with its fit and function at the one-year injury anniversary. High levels of respondent satisfaction with fit and function of WCs suggest clinicians are prescribing mobility devices adequately and accurately supplementing information obtained during equipment assessment and fitting sessions with information from general treatment sessions. Variation in type and frequency of WC training provided by level of SCI and in types of WC prescribed use provides a foundation for future research to relate treatment modalities with functional and participation outcomes. PMID- 26132350 TI - Prevalence of Sensor Saturation in Wheelchair Seat Interface Pressure Mapping. AB - Pressure mapping is a frequently used tool with great power to provide information about the forces between a patient and a wheelchair seat. One widely recognized limitation to this paradigm is the possibility of data loss due to sensor saturation. In this study, we seek to quantify and describe the saturation observed in the measurement of interface pressures of wheelchair users. We recorded approximately two minutes of interface pressure data from 22 elderly wheelchair users (11M/11F, 80 +/- 10 years) and found that 4.7% of data frames had 1 saturated sensor, and 9.0% had more than one saturated sensor, for a total of 13.7% of all frames of data. Data from three of the 22 subjects (13.6%) were substantially affected by the persistent presence of saturated sensors. We conclude that for this population of elderly wheelchair users, sensor saturation may be a concern and should be factored properly into study design a priori. PMID- 26132352 TI - Toilet Grab-Bar Preference and Center of Pressure Deviation During Toilet Transfers in Healthy Seniors, Seniors With Hip Replacements, and Seniors Having Suffered a Stroke. AB - Multiple toilet grab-bar configurations are required by people with a diverse spectrum of disability. The study purpose was to determine toilet grab-bar preference of healthy seniors, seniors with a hip replacement, and seniors post stroke, and to determine the effect of each configuration on centre of pressure (COP) displacement during toilet transfers. METHODS: 14 healthy seniors, 7 ambulatory seniors with a hip replacement, and 8 ambulatory seniors post-stroke participated in the study. Toilet transfers were performed with no bars (NB), commode (C), two vertical bars (2VB), one vertical bar (1VB), a horizontal bar (H), two swing-away bars (S) and a diagonal bar (D). COP was measured using pressure sensitive floor mats. Participants rated the safety, ease of use, helpfulness, comfort and preference for instalment. RESULTS: 2VB was most preferred and had the smallest COP deviation. Least preferred was H and NB. C caused largest COP displacement but had favourable ratings. DISCUSSION: The preference and safety of the 2VB should be considered in the design of accessible toilets and in accessibility construction guidelines. However these results need to be verified in non-ambulatory populations. C is frequently prescribed, but generates large COP deviation, suggesting it may present an increased risk of falls. PMID- 26132353 TI - Overview and Categorization of Robots Supporting Independent Living of Elderly People: What Activities Do They Support and How Far Have They Developed. AB - Over the past decades, many robots for the elderly have been developed, supporting different activities of elderly people. A systematic review in four scientific literature databases and a search in article references and European projects was performed in order to create an overview of robots supporting independent living of elderly people. The robots found were categorized based on their development stage, the activity domains they claim to support, and the type of support provided (i.e., physical, non-physical, and/or non-specified). In total, 107 robots for the elderly were identified. Six robots were still in a concept phase, 95 in a development phase, and six of these robots were commercially available. These robots claimed to provide support related to four activity domains: mobility, self-care, interpersonal interaction & relationships, and other activities. Of the many robots developed, only a small percentage is commercially available. Technical ambitions seem to be guiding robot development. To prolong independent living, the step towards physical support is inevitable and needs to be taken. However, it will be a long time before a robot will be capable of supporting multiple activities in a physical manner in the home of an elderly person in order to enhance their independent living. PMID- 26132354 TI - Augmentative and Alternative Communication System (AAC) for Social Inclusion of People With Complex Communication Needs in the Industry. AB - Inclusion of people with special needs in the labor market has been increasing in some regions of Brazil as a result of the Articles 6 and 7 of the Constitution of the Federal Republic of Brazil and the Quota Law (No. 8.213/91, Art. 93) which entitle people with disabilities to work in order to improve their social condition. To support persons with complex communication needs in the workplace, 40 graphic symbols termed "symbols of industrial expressions" were developed within the framework of the COMMUNIS package. The symbols were developed for a company of the food sector in the Metropolitan Region of Curitiba, Brazil. Individual interviews were held with the human resources professionals, as well as with employees with complex communication needs in order to identify problems, assess requirements, and generate a list of specific symbols to develop. The symbols were then validated with regard to their ease of recognition. Only five symbols needed revision. The results suggest that it is possible to develop a set of symbols for the workplace that are judged to be iconic by human resources professionals and employees with complex communication needs. PMID- 26132355 TI - Voice-Activated Lightweight Reacher to Assist with Upper Extremity Movement Limitations: A Case Study. AB - The focus of this research was to design a functional and user-friendly reacher for people with spinal cord injuries (SCIs). Engineering advancements have taken assistive robotics to new dimensions. Technologies such as wheelchair robotics and myo-electronically controlled systems have opened up a wide range of new applications to assist people with physical disabilities. Similarly, exo-skeletal limbs and body suits have provided new foundations from which technologies can aid function. Unfortunately, these devices have issues of usability, weight, and discomfort with donning. The Smart Assistive Reacher Arm (SARA) system, developed in this research, is a voice-activated, lightweight, mobile device that can be used when needed. SARA was built to help overcome daily reach challenges faced by individuals with limited arm and hand movement capability, such as people with cervical level 5-6 (C5-6) SCI. This article shows that a functional reacher arm with voice control can be beneficial for this population. Comparison study with healthy participants and an SCI participant shows that, when using SARA, a person with SCI can perform simple reach and grasp tasks independently, without someone else's help. This suggests that the interface is intuitive and can be easily used to a high level of proficiency by a SCI individual. PMID- 26132356 TI - Effect of a Wheelie Training Method With the Front Wheels on a Ramp in Novice Able-Bodied Participants: A Randomized Controlled Trial. AB - The objective of this study was to determine if wheelie training that begins with learning how to balance with the front wheels on a ramp would increase the success rate, reduce the training time, and improve retention rates. A randomized controlled trial design was used to evaluate the effectiveness of wheelie training on a ramp setting (ramp group, n = 26) and conventional training (conventional group, n = 26). The main outcome measures were success rates in achieving wheelie competence, training time, and the retention rate in 7 and 30 days respectively. The results showed that the success rate for each training group both reached 100%. The mean training times for the conventional group and the ramp group were 86.0 +/- 35.7 and 76.0 +/- 25.8 minutes. Training time was not significantly affected by the training method (p = 0.23), but it was affected by gender, with women requiring an average of 92.0 +/- 31.4 minutes in comparison with 70.0 +/- 27.5 minutes for men (p = 0.01). The skill retention rate after 7 and 30 days was 100% for both groups. Neither success rate nor training time for wheelie skill acquisition by learners were improved by learning wheelie balance on a ramp. However, a high retention rate of wheelie skills for both training groups was found, which implies that success can be achieved by training on a ramp used in this study. PMID- 26132357 TI - Robot-assisted rectal cancer surgery deserves a fair trial. PMID- 26132358 TI - Ingestion of food pellets containing Escherichia coli overexpressing the heat shock protein DnaK protects Penaeus vannamei (Boone) against Vibrio harveyi (Baumann) infection. AB - Feeding aquatic animals with bacterial encapsulated heat-shock proteins (Hsps) is potentially a new method to combat vibriosis, an important disease affecting aquatic animals used in aquaculture. Food pellets comprised of shrimp and containing Escherichia coli overexpressing either DnaK-DnaJ-GrpE, the prokaryotic equivalents of Hsp70-Hsp40-Hsp20, or only DnaK were fed to juveniles of the white leg shrimp Penaeus vannamei, and protection against pathogenic Vibrio harveyi was determined. Maintaining pellets at different temperatures for varying lengths of time reduced the number of live adhering E. coli, as did contact with sea water, demonstrating that storage and immersion adversely affected bacterial survival and attachment to pellets. Feeding P. vannamei with E. coli did not compromise their survival, indicating that the bacteria were not pathogenic to shrimp. Feeding P. vannamei with pellets containing bacteria overproducing DnaK (approximately 60 cells g(-1) pellets) boosted P. vannamei survival twofold against V. harveyi, suggesting that DnaK plays a role in Vibrio tolerance. Pellets containing DnaK were effective in providing protection to P. vannamei for up to 2 weeks before loss of viability and that DnaK encapsulated by these bacteria enhanced shrimp resistance against Vibrio infection. PMID- 26132359 TI - Proteome analysis in thyroid pathology. AB - The incidence of thyroid cancer has continuously increased due to its detection in the preclinical stage. Clinical research in thyroid pathology is focusing on the development of new diagnostic tools to improve the stratification of nodules that have biological, practical and economic consequences on the management of patients. Several clinical questions related to thyroid carcinoma remain open and the use of proteomic research in the hunt for new targets with potential diagnostic applications has an important role in the solutions. Many different proteomic approaches are used to investigate thyroid lesions, including mass spectrometry profiling and imaging technologies. These approaches have been applied to different human tissues (cytological specimens, frozen sections, formalin-fixed paraffin embedded tissue or Tissue Micro Arrays). Moreover, other specimens are used for biomarker discovery, such as cell lines and the secretome. Alternative approaches, such as metabolomics and lipidomics, are also used and integrated within proteomics. PMID- 26132360 TI - Strategies for appropriate antibiotic use in intensive care unit. AB - The comsumption of antibiotics is high, mainly in intensive care units. Unfortunately, most are inappropriately used leading to increased multi-resistant bacteria. It is well known that initial empirical therapy with broad-spectrum antibiotics reduce mortality rates. However the prolonged and irrational use of antimicrobials may also increase the risk of toxicity, drug interactions and diarrhea due to Clostridium difficile. Some strategies to rational use of antimicrobial agents include avoiding colonization treatment, de-escalation, monitoring serum levels of the agents, appropriate duration of therapy and use of biological markers. This review discusses the effectiveness of these strategies, the importance of microbiology knowledge, considering there are agents resistant to Staphylococcus aureus and Klebsiella pneumoniae, and reducing antibiotic use and bacterial resistance, with no impact on mortality. PMID- 26132361 TI - Giant prostatic hyperplasia: report of a previously asymptomatic man presenting with gross hematuria and hypovolemic shock. AB - Giant prostatic hyperplasia is a rare condition characterized by very high volume benign prostatic enlargement (>500g). Few cases have been reported so far and most of them are associated with severe lower urinary symptoms. We report the first case of asymptomatic giant prostatic hyperplasia in an elderly man who had a 720g prostate adenoma, sudden gross hematuria and hypovolemic shock. The patient was successfully treated with open transvesical prostatectomy and had an uneventful postoperative recovery. PMID- 26132362 TI - Extensive cervical lymphadenitis mimicking bacterial adenitis as the first presentation of Kawasaki disease. AB - Cervical adenitis >1.5cm in diameter is the less frequently observed criteria in patients with Kawasaki disease and it is usually found in association with other symptoms during the acute phase. Moreover, the finding of fever and lymphadenitis with intense local signs of inflammation and phlegmon is rarely seen as the initial manifestation of Kawasaki disease. We report the case of a 7-year-old boy who had cervical lymphadenitis with adjacent cellulitis and phlegmon mimicking bacterial adenitis as the first presentation of Kawasaki disease. The patient had fever, cervical lymphadenitis with adjacent cellulitis, and severe headache. Cefadroxil was prescribed based on the clinical diagnosis of bacterial adenitis. Because he remained febrile and phlogistic signs worsened, after 1 day of hospitalization, antibiotics were administrated intravenously (ceftriaxone and oxacillin). The computed tomography of the neck showed primary infectious/inflammatory process. On the fourth day, the patient had dry and scaly lips, and treatment with oxacillin was replaced by clindamycin because the patient was still febrile. On the ninth day, he presented non-exudative bilateral conjunctival injection. On the tenth day of febrile disease, a rash appeared on his trunk, hands and feet. Patient's symptoms resolved after intravenous administration of immunoglobulin (2g/kg/dose), and he was discharged 2 days later. On the 14th day, the patient had lamellar desquamation of fingers. Kawasaki disease should be considered as a differential diagnosis in children with febrile cervical lymphadenitis unresponsive to empiric antibiotics even if they have adjacent cellulitis and phlegmon. PMID- 26132363 TI - Association of Radial Margin Positivity With Colon Cancer. AB - IMPORTANCE: In colon cancer, radial margin positivity (RMP) is defined as primary disease involvement at the cut edge of the mesentery or nonserosalized portions of the colon. Although extensively studied for rectal malignancies, RMP has unclear prognostic implications for tumors of the colon. OBJECTIVE: To determine the effect of RMP on perioperative outcomes as well as survival and disease-free survival in colon cancer. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study including all patients with surgically treated colon cancer at a tertiary care center from January 1, 2004, through December 31, 2011. The cohort was retrospectively extracted from an institutional patient data repository and included in a data repository maintained prospectively starting June 1, 2011, to April 1, 2014. Participants included 984 patients with surgical colon cancer in the given period, excluding patients with intramucosal tumors (n = 47), palliative resections (n = 24), and patients where radial margin status was not assessable (n = 16). MAIN OUTCOMES AND MEASURES: Surgical characteristics, postoperative staging, and long-term outcomes, including recurrence and disease free survival. RESULTS: Of the 984 included cases, 52 (5.3%) had an involved radial margin. Patients with RMP had much higher rates of multivisceral resection (40.4% vs 12.8%; relative risk, 3.16 [95% CI, 2.18-4.58]; P < .001) and conversion (50.0% vs 13.7%; relative risk, 3.78 [95% CI, 1.56-9.18]; P = .01). All patients with RMP had American Joint Committee on Cancer stage II cancer or higher, with higher rates of node positivity (86.5% vs 38.8%; relative risk, 2.23 [95% CI, 1.95-2.55]; P < .001), metastasis (34.6% vs 6.7%; relative risk, 5.20 [95% CI, 3.34-8.11]; P < .001), extramural vascular invasion (76.9% vs 28.4%; relative risk, 2.71 [95% CI, 2.26-3.24]; P < .001), and high-grade tumor (45.1% vs 18.2%; relative risk, 3.01 [95% CI, 2.44-3.88]; P < .001). In patients without baseline metastasis, metastatic disease in follow-up was considerably higher in patients with RMP (37.5% vs 12.5%; relative risk, 3.32 [95% CI, 2.79-3.95]; P < .001), especially peritoneal (18.8% vs 2.6%; relative risk, 7.24 [95% CI, 2.40 21.8]; P < .001) and liver (18.8% vs 6%; relative risk, 3.10 [95% CI, 1.08-8.92]; P = .04) metastasis. In multivariable Cox regression, the hazard ratio for survival adjusted for baseline staging, age, comorbidity, smoking, and neoadjuvant chemotherapy was higher (hazard ratio, 3.39; 95% CI, 2.41-4.77; P < .001) compared with metastasis adjusted for baseline staging, smoking, and neoadjuvant chemotherapy (hazard ratio, 2.03; 95% CI, 1.43-2.89; P < .001). The median follow-up duration for patients alive on April 1, 2014, was 51 months (interquartile range, 33-76 months). CONCLUSIONS AND RELEVANCE: An involved radial margin leads to high rates of conversion and multivisceral resection. Although occurring infrequently, RMP is an important stage-independent outcome predictor strongly associated with recurrence, risk of death, and shorter survival. Preoperative assessment, especially imaging, could play a key role in the timely identification of potential patients with RMP to take adequate preparatory surgical and therapeutic measures. PMID- 26132364 TI - Using the TAT to Assess the Relation Between Gender Identity and the Use of Defense Mechanisms. AB - The purpose of this study is to explore whether 2 different dimensions of personality, when assessed at an implicit level with the Thematic Apperception Test (TAT; Murray, 1943 ) will show a theoretically meaningful coherence not demonstrated when 1 is assessed at an implicit level and the other at an explicit level. Gender identity and defense mechanisms were assessed implicitly using the TAT. Gender identity was compared with a self-report measure of gender-related attributes assessed at the explicit level. The results showed a theoretically meaningful coherence when different dispositions were assessed at the same level, but a lack of agreement when similar dispositions were assessed at different levels. The study is based on a secondary analysis of data from 2 previously published papers (Cramer, 1998 ; Cramer & Westergren, 1999 ). PMID- 26132365 TI - fMRI Validation of fNIRS Measurements During a Naturalistic Task. AB - We present a method to compare brain activity recorded with near-infrared spectroscopy (fNIRS) in a dance video game task to that recorded in a reduced version of the task using fMRI (functional magnetic resonance imaging). Recently, it has been shown that fNIRS can accurately record functional brain activities equivalent to those concurrently recorded with functional magnetic resonance imaging for classic psychophysical tasks and simple finger tapping paradigms. However, an often quoted benefit of fNIRS is that the technique allows for studying neural mechanisms of complex, naturalistic behaviors that are not possible using the constrained environment of fMRI. Our goal was to extend the findings of previous studies that have shown high correlation between concurrently recorded fNIRS and fMRI signals to compare neural recordings obtained in fMRI procedures to those separately obtained in naturalistic fNIRS experiments. Specifically, we developed a modified version of the dance video game Dance Dance Revolution (DDR) to be compatible with both fMRI and fNIRS imaging procedures. In this methodology we explain the modifications to the software and hardware for compatibility with each technique as well as the scanning and calibration procedures used to obtain representative results. The results of the study show a task-related increase in oxyhemoglobin in both modalities and demonstrate that it is possible to replicate the findings of fMRI using fNIRS in a naturalistic task. This technique represents a methodology to compare fMRI imaging paradigms which utilize a reduced-world environment to fNIRS in closer approximation to naturalistic, full-body activities and behaviors. Further development of this technique may apply to neurodegenerative diseases, such as Parkinson's disease, late states of dementia, or those with magnetic susceptibility which are contraindicated for fMRI scanning. PMID- 26132366 TI - Transfecting RAW264.7 Cells with a Luciferase Reporter Gene. AB - Transfection of desired genetic materials into cells is an inevitable procedure in biomedical research studies. While numerous methods have been described, certain types of cells are resistant to many of these methods and yield low transfection efficiency(1), potentially hindering research in those cell types. In this protocol, we present an optimized transfection procedure to introduce luciferase reporter genes as a plasmid DNA into the RAW264.7 macrophage cell line. Two different types of transfection reagents (lipid-based and polyamine based) are described, and important notes are given throughout the protocol to ensure that the RAW264.7 cells are minimally altered by the transfection procedure and any experimental data obtained are the direct results of the experimental treatment. While transfection efficiency may not be higher compared to other transfection methods, the described procedure is robust enough for detecting luciferase signal in RAW264.7 without changing the physiological response of the cells to stimuli. PMID- 26132367 TI - Induction Chemotherapy Followed by Concurrent Full-dose Gemcitabine and Intensity modulated Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma. AB - OBJECTIVE: To evaluate the outcomes and toxicity of concurrent full-dose gemcitabine and intensity-modulated radiation therapy (IMRT) for patients with borderline resectable and locally advanced pancreatic adenocarcinoma after induction chemotherapy. MATERIALS AND METHODS: From 2009 to 2012, 32 patients were treated with concurrent gemcitabine and IMRT for borderline resectable or locally advanced pancreatic adenocarcinoma. All patients received induction FOLFIRINOX or gemcitabine-based chemotherapy before chemoradiation. The radiotherapy volume was limited to the primary tumor, and the median dose was 55 Gy in 25 fractions. Gemcitabine was administered weekly during radiotherapy on days 1, 8, 22, and 29 at a median weekly dose of 800 mg/m2. RESULTS: Twenty-five patients had locally advanced disease and 7 had borderline resectable disease. The median follow-up time was 14.6 months. The median progression-free and overall survival were 13.9 and 23.1 months, with a trend toward improved overall survival for patients receiving induction FOLFIRINOX compared with gemcitabine based therapy. A radiographic complete or partial response was achieved in 13 patients (41%), with 4 (13%) having complete radiographic responses. Surgical resection was performed in 10 patients (31%)--6 patients with locally advanced disease and 4 with borderline resectable disease. Grade 3/4 hematologic toxicity during and up to 6 weeks after chemoradiation occurred in 12 patients (38%); grade 3 nonhematologic toxicity occurred in 7 patients (22%), with no grade 4 or 5 toxicity. All patients completed their radiotherapy. CONCLUSIONS: Concurrent full-dose gemcitabine and limited-field IMRT after induction chemotherapy for the treatment of borderline resectable and locally advanced pancreatic cancer is promising with acceptable toxicity rates. PMID- 26132368 TI - Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo. AB - Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment. PMID- 26132369 TI - Dealing with the moral distress of "reality shock". PMID- 26132370 TI - 20 questions: Evidence-based practice or sacred cow? PMID- 26132371 TI - Parental attachment, self-control, and depressive symptoms in Chinese and Italian adolescents: Test of a mediation model. AB - The current study investigated the relationship between parental attachment and depressive symptoms as well as the mediating effect of self-control in two different cultures. Samples were 1305 Chinese and 1327 Italian adolescents. They completed the Inventory of Parental and Peer Attachment, the Self-Restraint Subscale of the Adolescents' Self-Consciousness Scale, and the Children's Depression Inventory that assessed parental attachment, self-control, and depressive symptoms, respectively. Results showed that: (1) Few cultural differences in depressive symptom were observed. (2) Parental attachment and self control were negatively related to depressive symptoms in both cultures. (3) Self control mediated the relations between parental attachment and depressive symptoms in both cultures. (4) The direct and indirect effects were invariant across cultures. In conclusion, parental attachment and self-control are important for adolescents' depressive symptoms in Chinese and Italian adolescents. PMID- 26132372 TI - Investigating DNA methylation dynamics and safety of human embryonic stem cell differentiation toward striatal neurons. AB - The potential use of human embryonic stem cells (hESCs) in cell-based therapies points out the critical importance of epigenomic evaluation for cell-based therapies. Specifically, DNA methylation appears to be a crucial player in establishing cell fate commitment and lineage choices. In this study, we report the global changes observed on the CpG islands distributed in promoters, gene bodies, and intergenic regions and the major biochemical pathways and genes involved in methylation changes as H9-hESCs turn into a neuronal culture containing medium-sized spiny striatal neurons (MSNs). Using an ontogeny recapitulating protocol of striatal neuron differentiation, we analyzed DNA methylation profiles during the conversion from pluripotency to neuropotency up to the acquisition of a mature neuronal phenotype. H9-hESCs changed the methylation pattern both through de novo methylation and hypomethylation of specific gene promoters. Bioinformatic analysis allowed us to identify a panel of striatal-associated genes, which were regulated by DNA methylation and differentially expressed during striatal commitment. Importantly, DNA methylation analysis revealed that H9-hESCs did not acquire methylation-based oncogenic properties after differentiation. Indeed, hypermethylation of cancer-associated genes that characterize transformed cells, such as Polycomb repressive complex associated genes, was not detected in the neuronal cultures. However, the oncosuppressor gene, BCL2L11, became hypermethylated in H9-hESC-derived mature neurons. Whole-genome DNA methylation profiling could become a technological platform to predict the differentiative potential of hESC-derived cultures and establish further biosafety assessment quality control tools of the cell-based products. PMID- 26132374 TI - Real Time Quantification of Ultrafast Photoinduced Bimolecular Electron Transfer Rate: Direct Probing of the Transient Intermediate. AB - Fluorescence quenching studies through steady-state and time-resolved measurements are inadequate to quantify the bimolecular electron transfer rate in bulk homogeneous solution due to constraints from diffusion. To nullify the effect of diffusion, direct evaluation of the rate of formation of a transient intermediate produced upon the electron transfer is essential. Methyl viologen, a well-known electron acceptor, produces a radical cation after accepting an electron, which has a characteristic strong and broad absorption band centered at 600 nm. Hence it is a good choice to evaluate the rate of photoinduced electron transfer reaction employing femtosecond broadband transient absorption spectroscopy. The time constant of the aforementioned process between pyrene and methyl viologen in methanol has been estimated to be 2.5 +/- 0.4 ps using the same technique. The time constant for the backward reaction was found to be 14 +/ 1 ps. These values did not change with variation of concentration of quencher, i.e., methyl viologen. Hence, we can infer that diffusion has no contribution in the estimation of rate constants. However, on changing the solvent from methanol to ethanol, the time constant of the electron transfer reaction has been found to increase and has accounted for the change in solvent reorganization energy. PMID- 26132373 TI - Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology. AB - We discuss considerations that are essential when evaluating exposure to nonpersistent, semivolatile environmental chemicals such as phthalates and phenols (e.g., bisphenol A). A biomarker should be chosen to best represent usual personal exposures and not recent, adventitious, or extraneous exposures. Biomarkers should be selected to minimize contamination arising from collection, sampling, or analysis procedures. Pharmacokinetics should be considered; for example, nonpersistent, semivolatile chemicals are metabolized quickly, and urine is the compartment with the highest concentrations of metabolites. Because these chemicals are nonpersistent, knowledge of intraindividual reliability over the biologic window of interest is also required. In recent years researchers have increasingly used blood as a matrix for characterizing exposure to nonpersistent chemicals. However, the biologic and technical factors noted above strongly support urine as the optimal matrix for measuring nonpersistent, semivolatile, hydrophilic environmental agents. PMID- 26132375 TI - Solution Dynamics of Redox Noninnocent Nitrosoarene Ligands: Mapping the Electronic Criteria for the Formation of Persistent Metal-Coordinated Nitroxide Radicals. AB - The redox-noninnocence of metal-coordinated C-organo nitrosoarenes has been established on the basis of solid-state characterization techniques, but the solution-phase properties of this class of metal-coordinated radicals have been relatively underexplored. In this report, the solution-phase properties and dynamics of the bis-nitrosobenzene diradical complex trans-Pd(kappa(1)-N PhNO)2(CNAr(Dipp2))2 are presented. This complex, which is best described as containing singly reduced phenylnitroxide radical ligands, is shown to undergo facile nitrosobenzene dissociation in solution to form the metalloxaziridine Pd(eta(2)-N,O-PhNO)(CNAr(Dipp2))2 and thus is not a persistent species in solution. An equilibrium between trans-Pd(kappa(1)-N-PhNO)2(CNAr(Dipp2))2, Pd(eta(2)-N,O-PhNO)(CNAr(Dipp2))2, and free nitrosobenzene is established in solution, with the metalloxaziridine being predominantly favored. Efforts to perturb this equilibrium by the addition of excess nitrosobenzene reveal that the formation of trans-Pd(kappa(1)-N-PhNO)2(CNAr(Dipp2))2 is in competition with insertion-type chemistry of Pd(eta(2)-N,O-PhNO)(CNAr(Dipp2))2 and is therefore not a viable strategy for the production of a kinetically persistent bis nitroxide radical complex. Electronic modification of the nitrosoarene framework was explored as a means to generate a persistent trans-Pd(kappa(1)-N ArNO)2(CNAr(Dipp2))2 complex. While most substitution schemes failed to significantly perturb the kinetic lability of the nitrosoarene ligands in the corresponding trans-Pd(kappa(1)-N-ArNO)2(CNAr(Dipp2))2 complexes, utilization of para-formyl or para-cyano nitrosobenzene produced bis-nitroxide diradical complexes that display kinetic persistence in solution. The origin of this persistence is rationalized by the ability of para-formyl- and para-cyano-aryl groups to both attenuate the trans effect of the corresponding nitrosoarene and, more importantly, delocalize spin density away from the aryl-nitroxide NO unit. The results presented here highlight the inherent instability of metal coordinated nitroxide radicals and suggest a general synthetic strategy for kinetically stabilizing these species in solution. PMID- 26132376 TI - Non-Alcoholic Fatty Liver Disease (NAFLD) in children and adolescents with Prader Willi Syndrome (PWS). AB - We tested the hypothesis that patients with Prader-Willi syndrome (PWS) may be at lower risk of developing non-alcoholic fatty liver disease (NAFLD) because of a higher insulin sensitivity. Twenty-one PWS patients and 42 control subjects closely similar for age, gender, pubertal stage and body mass index (CNT), were studied. Metabolic profile and body composition were assessed. NAFLD was established by a validated method of US grading (range from G0 to G3). PWS patients showed a significantly better metabolic profile (lower waist circumference, fasting glucose levels, HOMA-IR, cholesterol, transaminase levels and trunk fat mass/fat mass ratio). Furthermore, NAFLD G1stage was significantly more frequent in PWS subjects (P < 0.05), whereas G2 stage was significantly more frequent in control patients (P < 0.05). NAFLD grading seems to correlate with body composition in PWS, also after adjustment for sex and GH treatment. To our knowledge, this is the first report suggesting a reduced risk of NAFLD in PWS children. PMID- 26132377 TI - What influences retrospective self-appraised recovery status among Danes with low back problems? A comparative qualitative investigation. AB - STUDY DESIGN: Phenomenological, qualitative investigation. The discord between commonly used outcome measures and patients' self-perceived recovery is problematic in the investigation and rehabilitation of low-back pain-related disorders. To better understand the course and development of this costly and disabling condition, the complex process of patient recovery requires further elucidation. OBJECTIVE: To explore issues and experiences impacting retrospective, self-appraised recovery. METHODS: Semi-structured interviews were conducted with 32 purposively sampled individuals, after which computer-assisted substantive categorization and thematic analysis was performed. RESULTS: Self appraised status could be determined as "recovered" for 17 respondents, "unsure" for 6, and "not recovered" for 9. Recovery/non-recovery hinged on continued pain related issues and the perception that injury/trauma made recovery impossible. Individuals who had difficulties relating the recovery construct to their context as well as those who were sceptical of pain-free periods were unable to appraise their status. CONCLUSION: This investigation confirms that pain is central to the resolution of recurrent low-back pain associated disorders. However, recovery also involves "redefinition" and "readjustment". In the investigation and rehabilitation of ambiguous, regional musculoskeletal disorders, our results provide further sensitizing concepts, derived through naturalistic observation, that are useful in the development of a more comprehensive explanatory framework of patient recovery. PMID- 26132378 TI - Brine-Stabilized 2,2,2-Trifluorodiazoethane and Its Application in the Synthesis of CF3-Substituted Cyclopropane alpha-Amino Acids. AB - A facile thermodynamic cyclopropanation of trisubstituted olefinic azlactones with a stock solution of CF3CHN2 in CH3CN is realized. This method shows excellent generality, affording a wide range of trifluoromethyl-substituted cyclopropanes bearing azlactone rings in good to high yields and diastereoselectivities. With the products in hand, the trifluoromethyl substituted cyclopropane alpha-amino acids and relative peptide derivatives could be readily obtained. PMID- 26132379 TI - Collision-Induced Dissociation Mass Spectrometry: A Powerful Tool for Natural Product Structure Elucidation. AB - Mass spectrometry is a powerful tool in natural product structure elucidation, but our ability to directly correlate fragmentation spectra to these structures lags far behind similar efforts in peptide sequencing and proteomics. Often, manual data interpretation is required and our knowledge of the expected fragmentation patterns for many scaffolds is limited, further complicating analysis. Here, we summarize advances in natural product structure elucidation based upon the application of collision induced dissociation fragmentation mechanisms. PMID- 26132380 TI - Metal-silicate Partitioning at High Pressure and Temperature: Experimental Methods and a Protocol to Suppress Highly Siderophile Element Inclusions. AB - Estimates of the primitive upper mantle (PUM) composition reveal a depletion in many of the siderophile (iron-loving) elements, thought to result from their extraction to the core during terrestrial accretion. Experiments to investigate the partitioning of these elements between metal and silicate melts suggest that the PUM composition is best matched if metal-silicate equilibrium occurred at high pressures and temperatures, in a deep magma ocean environment. The behavior of the most highly siderophile elements (HSEs) during this process however, has remained enigmatic. Silicate run-products from HSE solubility experiments are commonly contaminated by dispersed metal inclusions that hinder the measurement of element concentrations in the melt. The resulting uncertainty over the true solubility and metal-silicate partitioning of these elements has made it difficult to predict their expected depletion in PUM. Recently, several studies have employed changes to the experimental design used for high pressure and temperature solubility experiments in order to suppress the formation of metal inclusions. The addition of Au (Re, Os, Ir, Ru experiments) or elemental Si (Pt experiments) to the sample acts to alter either the geometry or rate of sample reduction respectively, in order to avoid transient metal oversaturation of the silicate melt. This contribution outlines procedures for using the piston cylinder and multi-anvil apparatus to conduct solubility and metal-silicate partitioning experiments respectively. A protocol is also described for the synthesis of uncontaminated run-products from HSE solubility experiments in which the oxygen fugacity is similar to that during terrestrial core-formation. Time resolved LA-ICP-MS spectra are presented as evidence for the absence of metal inclusions in run-products from earlier studies, and also confirm that the technique may be extended to investigate Ru. Examples are also given of how these data may be applied. PMID- 26132381 TI - Genome-, Transcriptome- and Proteome-Wide Analyses of the Gliadin Gene Families in Triticum urartu. AB - Gliadins are the major components of storage proteins in wheat grains, and they play an essential role in the dough extensibility and nutritional quality of flour. Because of the large number of the gliadin family members, the high level of sequence identity, and the lack of abundant genomic data for Triticum species, identifying the full complement of gliadin family genes in hexaploid wheat remains challenging. Triticum urartu is a wild diploid wheat species and considered the A-genome donor of polyploid wheat species. The accession PI428198 (G1812) was chosen to determine the complete composition of the gliadin gene families in the wheat A-genome using the available draft genome. Using a PCR based cloning strategy for genomic DNA and mRNA as well as a bioinformatics analysis of genomic sequence data, 28 gliadin genes were characterized. Of these genes, 23 were alpha-gliadin genes, three were gamma-gliadin genes and two were omega-gliadin genes. An RNA sequencing (RNA-Seq) survey of the dynamic expression patterns of gliadin genes revealed that their synthesis in immature grains began prior to 10 days post-anthesis (DPA), peaked at 15 DPA and gradually decreased at 20 DPA. The accumulation of proteins encoded by 16 of the expressed gliadin genes was further verified and quantified using proteomic methods. The phylogenetic analysis demonstrated that the homologs of these alpha-gliadin genes were present in tetraploid and hexaploid wheat, which was consistent with T. urartu being the A-genome progenitor species. This study presents a systematic investigation of the gliadin gene families in T. urartu that spans the genome, transcriptome and proteome, and it provides new information to better understand the molecular structure, expression profiles and evolution of the gliadin genes in T. urartu and common wheat. PMID- 26132383 TI - Valuing Reductions in Fatal Illness Risks: Implications of Recent Research. AB - The value of mortality risk reductions, conventionally expressed as the value per statistical life, is an important determinant of the net benefits of many government policies. US regulators currently rely primarily on studies of fatal injuries, raising questions about whether different values might be appropriate for risks associated with fatal illnesses. Our review suggests that, despite the substantial expansion of the research base in recent years, few US studies of illness-related risks meet criteria for quality, and those that do yield similar values to studies of injury-related risks. Given this result, combining the findings of these few studies with the findings of the more robust literature on injury-related risks appears to provide a reasonable range of estimates for application in regulatory analysis. Our review yields estimates ranging from about $4.2 million to $13.7 million with a mid-point of $9.0 million (2013 dollars). Although the studies we identify differ from those that underlie the values currently used by Federal agencies, the resulting estimates are remarkably similar, suggesting that there is substantial consensus emerging on the values applicable to the general US population. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26132382 TI - ITS2 Secondary Structure Improves Discrimination between Medicinal "Mu Tong" Species when Using DNA Barcoding. AB - DNA barcoding is a promising species identification method, but it has proved difficult to find a standardized DNA marker in plant. Although the ITS/ITS2 RNA transcript has been proposed as the core barcode for seed plants, it has been criticized for being too conserved in some species to provide enough information or too variable in some species to align it within the different taxa ranks. We selected 30 individuals, representing 16 species and four families, to explore whether ITS2 can successfully resolve species in terms of secondary structure. Secondary structure was predicted using Mfold software and sequence-structure was aligned by MARNA. RNAstat software transformed the secondary structures into 28 symbol code data for maximum parsimony (MP) analysis. The results showed that the ITS2 structures in our samples had a common four-helix folding type with some shared motifs. This conserved structure facilitated the alignment of ambiguous sequences from divergent families. The structure alignment yielded a MP tree, in which most topological relationships were congruent with the tree constructed using nucleotide sequence data. When the data was combined, we obtained a well resolved and highly supported phylogeny, in which individuals of a same species were clustered together into a monophyletic group. As a result, the different species that are often referred to as the herb "Mu tong" were successfully identified using short fragments of 250 bp ITS2 sequences, together with their secondary structure. Thus our analysis strengthens the potential of ITS2 as a promising DNA barcode because it incorporates valuable secondary structure information that will help improve discrimination between species. PMID- 26132384 TI - Improved Stress Control in Serotonin Transporter Knockout Rats: Involvement of the Prefrontal Cortex and Dorsal Raphe Nucleus. AB - Variations in serotonin transporter (5-HTT) expression have been associated with altered sensitivity to stress. Since controllability is known to alter the impact of a stressor through differential activation of the medial prefrontal cortex (mPFC) and dorsal raphe nucleus (DRN), and that these regions are functionally affected by genetic 5-HTT down-regulation, we hypothesized that 5-HTT expression modulates the effect of controllability on stressor impact and coping. Here, we investigated the effects of a signaled stress controllability task or a yoked uncontrollable stressor on behavioral responding and mPFC and DRN activation. 5 HTT(-/-) rats proved better capable of acquiring the active avoidance task than 5 HTT(+/+) animals. Controllability determined DRN activation in 5-HTT(+/+), but not 5-HTT(-/-), rats, whereas controllability-related activation of the mPFC was independent of genotype. These findings suggest that serotonergic activation in the DRN is involved in stress coping in a 5-HTT expression dependent manner, whereas mPFC activation seems to be implicated in control over stress independently of 5-HTT expression. We speculate that alterations in serotonergic feedback in the DRN might be a potential mechanism driving this differential stress coping. PMID- 26132386 TI - Gates, Bloomberg establish fund to fight tobacco industry worldwide: Effort aims to assist low-income countries. PMID- 26132387 TI - ASCO report highlights challenges in delivering high-quality care. PMID- 26132388 TI - Majority of survivors of childhood cancer experience comorbidities. PMID- 26132389 TI - Mersch J, Jackson MA, Park M, Nebgen D, Peterson SK, Singletary C, Arun BK and Litton JK. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121:269-275. PMID- 26132391 TI - Uremic Toxins Induce ET-1 Release by Human Proximal Tubule Cells, which Regulates Organic Cation Uptake Time-Dependently. AB - In renal failure, the systemic accumulation of uremic waste products is strongly associated with the development of a chronic inflammatory state. Here, the effect of cationic uremic toxins on the release of inflammatory cytokines and endothelin 1 (ET-1) was investigated in conditionally immortalized proximal tubule epithelial cells (ciPTEC). Additionally, we examined the effects of ET-1 on the cellular uptake mediated by organic cation transporters (OCTs). Exposure of ciPTEC to cationic uremic toxins initiated production of the inflammatory cytokines IL-6 (117 +/- 3%, p < 0.001), IL-8 (122 +/- 3%, p < 0.001), and ET-1 (134 +/- 5%, p < 0.001). This was accompanied by a down-regulation of OCT mediated 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP+) uptake in ciPTEC at 30 min (23 +/- 4%, p < 0.001), which restored within 60 min of incubation. Exposure to ET-1 for 24 h increased the ASP+ uptake significantly (20 +/- 5%, p < 0.001). These effects could be blocked by BQ-788, indicating activation of an ET-B-receptor-mediated signaling pathway. Downstream the receptor, iNOS inhibition by (N(G)-monomethyl-l-arginine) l-NMMA acetate or aminoguanidine, as well as protein kinase C activation, ameliorated the short term effects. These results indicate that uremia results in the release of cytokines and ET-1 from human proximal tubule cells, in vitro. Furthermore, ET-1 exposure was found to regulate proximal tubular OCT transport activity in a differential, time-dependent, fashion. PMID- 26132392 TI - Influenza vaccination in patients with cancer: factors associated with vaccination practices for patients and their household members. AB - Presented in part: IDWeek 2014; Philadelphia, PA; October 8-12, 2014 (Poster 1120). PMID- 26132393 TI - Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial. AB - BACKGROUND: Low/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized. METHODS: 1016 adults (692 men, 324 postmenopausal women) underwent double-blind sex-stratified randomization to placebo, simvastatin 20mg, or pravastatin 40mg (6 months). The Overt-Aggression Scale-Modified-Aggression-Subscale (OASMa) assessed behavioral aggression. A significant sex-statin interaction was deemed to dictate sex-stratified analysis. Exploratory analyses assessed the influence of baseline-aggression, testosterone change (men), sleep and age. RESULTS: The sex-statin interaction was significant (P=0.008). In men, statins tended to decrease aggression, significantly so on pravastatin: difference=-1.0(SE=0.49)P=0.038. Three marked outliers (OASMa-change >=40 points) offset otherwise strong significance-vs-placebo: statins: 1.3(SE=0.38)P=0.0007; simvastatin:-1.4(SE=0.43)P=0.0011; pravastatin: 1.2(SE=0.45)P=0.0083. Age<=40 predicted greater aggression-decline on statins: difference=-1.4(SE=0.64)P=0.026. Aggression-protection was emphasized in those with low baseline aggression: age<40-and-low-baseline-aggression (N=40) statin difference-vs-placebo=-2.4(SE=0.71)P=0.0016. Statins (especially simvastatin) lowered testosterone, and increased sleep problems. Testosterone-drop on statins predicted aggression-decline: beta=0.64(SE=0.30)P=0.034, particularly on simvastatin: beta=1.29(SE=0.49)P=0.009. Sleep-worsening on statins significantly predicted aggression-increase: beta=2.2(SE=0.55)P<0.001, particularly on simvastatin (potentially explaining two of the outliers): beta=3.3(SE=0.83)P<0.001. Among (postmenopausal) women, a borderline aggression increase on statins became significant with exclusion of one younger, surgically menopausal woman (N=310) beta=0.70(SE=0.34)P=0.039. The increase was significant, without exclusions, for women of more typical postmenopausal age (>=45): (N=304) beta=0.68(SE=0.34)P=0.048 - retaining significance with modified age-cutoffs (>=50 or >=55). Significance was observed separately for simvastatin. The aggression-increase in women on statins was stronger in those with low baseline aggression (N=175) beta=0.84(SE=0.30)P=0.006. No statin effect on whole blood serotonin was observed; and serotonin-change did not predict aggression-change. CONCLUSION: Statin effects on aggression differed by sex and age: Statins generally decreased aggression in men; and generally increased aggression in women. Both findings were selectively prominent in participants with low baseline aggression - bearing lower change-variance, rendering an effect more readily evident. TRIAL REGISTRATION: Clinicaltrials.gov NCT00330980. PMID- 26132394 TI - An Algorithm for Protein Helix Assignment Using Helix Geometry. AB - Helices are one of the most common and were among the earliest recognized secondary structure elements in proteins. The assignment of helices in a protein underlies the analysis of its structure and function. Though the mathematical expression for a helical curve is simple, no previous assignment programs have used a genuine helical curve as a model for helix assignment. In this paper we present a two-step assignment algorithm. The first step searches for a series of bona fide helical curves each one best fits the coordinates of four successive backbone Calpha atoms. The second step uses the best fit helical curves as input to make helix assignment. The application to the protein structures in the PDB (protein data bank) proves that the algorithm is able to assign accurately not only regular alpha-helix but also 310 and pi helices as well as their left-handed versions. One salient feature of the algorithm is that the assigned helices are structurally more uniform than those by the previous programs. The structural uniformity should be useful for protein structure classification and prediction while the accurate assignment of a helix to a particular type underlies structure function relationship in proteins. PMID- 26132396 TI - The Behavioral Space of Zebrafish Locomotion and Its Neural Network Analog. AB - How simple is the underlying control mechanism for the complex locomotion of vertebrates? We explore this question for the swimming behavior of zebrafish larvae. A parameter-independent method, similar to that used in studies of worms and flies, is applied to analyze swimming movies of fish. The motion itself yields a natural set of fish "eigenshapes" as coordinates, rather than the experimenter imposing a choice of coordinates. Three eigenshape coordinates are sufficient to construct a quantitative "postural space" that captures >96% of the observed zebrafish locomotion. Viewed in postural space, swim bouts are manifested as trajectories consisting of cycles of shapes repeated in succession. To classify behavioral patterns quantitatively and to understand behavioral variations among an ensemble of fish, we construct a "behavioral space" using multi-dimensional scaling (MDS). This method turns each cycle of a trajectory into a single point in behavioral space, and clusters points based on behavioral similarity. Clustering analysis reveals three known behavioral patterns-scoots, turns, rests-but shows that these do not represent discrete states, but rather extremes of a continuum. The behavioral space not only classifies fish by their behavior but also distinguishes fish by age. With the insight into fish behavior from postural space and behavioral space, we construct a two-channel neural network model for fish locomotion, which produces strikingly similar postural space and behavioral space dynamics compared to real zebrafish. PMID- 26132395 TI - The bZIP Transcription Factor HAC-1 Is Involved in the Unfolded Protein Response and Is Necessary for Growth on Cellulose in Neurospora crassa. AB - High protein secretion capacity in filamentous fungi requires an extremely efficient system for protein synthesis, folding and transport. When the folding capacity of the endoplasmic reticulum (ER) is exceeded, a pathway known as the unfolded protein response (UPR) is triggered, allowing cells to mitigate and cope with this stress. In yeast, this pathway relies on the transcription factor Hac1, which mediates the up-regulation of several genes required under these stressful conditions. In this work, we identified and characterized the ortholog of the yeast HAC1 gene in the filamentous fungus Neurospora crassa. We show that its mRNA undergoes an ER stress-dependent splicing reaction, which in N. crassa removes a 23 nt intron and leads to a change in the open reading frame. By disrupting the N. crassa hac-1 gene, we determined it to be crucial for activating UPR and for proper growth in the presence of ER stress-inducing chemical agents. Neurospora is naturally found growing on dead plant material, composed primarily by lignocellulose, and is a model organism for the study of plant cell wall deconstruction. Notably, we found that growth on cellulose, a substrate that requires secretion of numerous enzymes, imposes major demands on ER function and is dramatically impaired in the absence of hac-1, thus broadening the range of physiological functions of the UPR in filamentous fungi. Growth on hemicellulose however, another carbon source that necessitates the secretion of various enzymes for its deconstruction, is not impaired in the mutant nor is the amount of proteins secreted on this substrate, suggesting that secretion, as a whole, is unaltered in the absence of hac-1. The characterization of this signaling pathway in N. crassa will help in the study of plant cell wall deconstruction by fungi and its manipulation may result in important industrial biotechnological applications. PMID- 26132397 TI - Small-World Brain Network and Dynamic Functional Distribution in Patients with Subcortical Vascular Cognitive Impairment. AB - To investigate the topological properties of the functional connectivity and their relationships with cognition impairment in subcortical vascular cognitive impairment (SVCI) patients, resting-state fMRI and graph theory approaches were employed in 23 SVCI patients and 20 healthy controls. Functional connectivity between 90 brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Moreover, all of them were subjected to a battery of cognitive assessment, and the correlations between graph metrics and cognitive performance were further analyzed. Our results are as follows: functional brain networks of both SVCI patients and controls showed small-world attributes over a range of thresholds(0.15<=sparsity<=0.40). However, global topological organization of the functional brain networks in SVCI was significantly disrupted, as indicated by reduced global and local efficiency, clustering coefficients and increased characteristic path lengths relative to normal subjects. The decreased activity areas in SVCI predominantly targeted in the frontal-temporal lobes, while subcortical regions showed increased topological properties, which are suspected to compensate for the inefficiency of the functional network. We also demonstrated that altered brain network properties in SVCI are closely correlated with general cognitive and praxis dysfunction. The disruption of whole-brain topological organization of the functional connectome provides insight into the functional changes in the human brain in SVCI. PMID- 26132398 TI - Corrigendum: Ecto-domain phosphorylation promotes functional recovery from spinal cord injury. PMID- 26132407 TI - A Dilemma: Premature Thelarche or Normal Pubertal Development. PMID- 26132406 TI - Nisin ZP, a Bacteriocin and Food Preservative, Inhibits Head and Neck Cancer Tumorigenesis and Prolongs Survival. AB - The use of small antimicrobial peptides or bacteriocins, like nisin, to treat cancer is a new approach that holds great promise. Nisin exemplifies this new approach because it has been used safely in humans for many years as a food preservative, and recent laboratory studies support its anti-tumor potential in head and neck cancer. Previously, we showed that nisin (2.5%, low content) has antitumor potential in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. The current studies explored a naturally occurring variant of nisin (nisin ZP; 95%, high content) for its antitumor effects in vitro and in vivo. Nisin ZP induced the greatest level of apoptosis in HNSCC cells compared to low content nisin. HNSCC cells treated with increasing concentrations of nisin ZP exhibited increasing levels of apoptosis and decreasing levels of cell proliferation, clonogenic capacity, and sphere formation. Nisin ZP induced apoptosis through a calpain-dependent pathway in HNSCC cells but not in human oral keratinocytes. Nisin ZP also induced apoptosis dose-dependently in human umbilical vein endothelial cells (HUVEC) with concomitant decreases in vascular sprout formation in vitro and reduced intratumoral microvessel density in vivo. Nisin ZP reduced tumorigenesis in vivo and long-term treatment with nisin ZP extended survival. In addition, nisin treated mice exhibited normal organ histology with no evidence of inflammation, fibrosis or necrosis. In summary, nisin ZP exhibits greater antitumor effects than low content nisin, and thus has the potential to serve as a novel therapeutic for HNSCC. PMID- 26132409 TI - Allele frequencies of human platelet antigens in Banjar, Bugis, Champa, Jawa and Kelantan Malays in Peninsular Malaysia. AB - OBJECTIVES: The major aims of this study are to characterise and compile allelic data of human platelet antigen (HPA)-1 to -6 and -15 systems in five Malay sub ethnic groups in Peninsular Malaysia. BACKGROUND: HPAs are polymorphic glycoproteins expressed on the surface of platelet membranes and are genetically differentiated across ethnogeographically unrelated populations. METHODS: Blood samples were obtained with informed consent from 192 volunteers: Banjar (n = 30), Bugis (n = 37), Champa (n = 51), Jawa (n = 39) and Kelantan (n = 35). Genotyping was done using polymerase chain reaction-sequence specific primer method. RESULTS: In general, frequencies of HPAs in the Malay sub-ethnic groups are more similar to those in Asian populations compared with other more distinct populations such as Indians, Australian Aborigines and Europeans. CONCLUSIONS: This study provides the first HPA datasets for the selected Malay sub-ethnic groups. Subsequent analyses including previously reported HPA data of Malays, Chinese and Indians revealed details of the genetic relationships and ancestry of various sub-populations in Peninsular Malaysia. Furthermore, the comprehensive HPA allele frequency information from Peninsular Malaysia provided in this report has potential applications for future study of diseases, estimating risks associated with HPA alloimmunization and for developing an efficient HPA-typed donor recruitment strategy. PMID- 26132408 TI - The Catalytic and Non-catalytic Functions of the Brahma Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in Drosophila. AB - Daily rhythms in gene expression play a critical role in the progression of circadian clocks, and are under regulation by transcription factor binding, histone modifications, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Although previous studies have shown that clock controlled genes exhibit rhythmic chromatin modifications, less is known about the functions performed by chromatin remodelers in animal clockwork. Here we have identified the Brahma (Brm) complex as a regulator of the Drosophila clock. In Drosophila, CLOCK (CLK) is the master transcriptional activator driving cyclical gene expression by participating in an auto-inhibitory feedback loop that involves stimulating the expression of the main negative regulators, period (per) and timeless (tim). BRM functions catalytically to increase nucleosome density at the promoters of per and tim, creating an overall restrictive chromatin landscape to limit transcriptional output during the active phase of cycling gene expression. In addition, the non-catalytic function of BRM regulates the level and binding of CLK to target promoters and maintains transient RNAPII stalling at the per promoter, likely by recruiting repressive and pausing factors. By disentangling its catalytic versus non-catalytic functions at the promoters of CLK target genes, we uncovered a multi-leveled mechanism in which BRM fine-tunes circadian transcription. PMID- 26132410 TI - Plasmonic Ag Core-Satellite Nanostructures with a Tunable Silica-Spaced Nanogap for Surface-Enhanced Raman Scattering. AB - Plasmonic Ag core-satellite nanostructures were synthesized by utilizing the ultrathin silica shell as a spacer to generate a tunable nanogap between the Ag core and satellites. To synthesize the nanoparticles, Ag nanoparticles (Ag NPs) with a diameter of ~60 nm were synthesized as cores, on which Raman dyes were adsorbed and then tunable ultrathin silica shells from 2.0 to 6.5 nm were coated, followed by the deposition of Ag NPs as satellites onto the silica surface. The relationships between the SERS signal and the important parameters, including the satellite diameter and the nanogap distance, were studied by experimental methods and theoretical calculations. The maximum SERS intensity of the core-satellite nanoparticles was over 14.6 times stronger than that of the isolated Raman encoded Ag/PATP@SiO2 NP. The theoretical calculations indicated that the local maximum calculated enhancement factor (EF) of the hot spots with a 2.0 nm nanogap was 9.5 * 10(5). The well-defined Ag core-satellite nanostructures have a high structural uniformity and an anomalously strong electromagnetic enhancement for highly quantitative SERS, leading to a better understanding of hot spot formation and providing new insights into the optimal design and synthesis of the hot SERS nanostructures in a controlled manner. PMID- 26132412 TI - Synergy Potential of Indole Alkaloids and Its Derivative against Drug-resistant Escherichia coli. AB - Antibacterial and synergy potential of naturally occurring indole alkaloids (IA): 10-methoxy tetrahydroalstonine (1), isoreserpiline (2), 10 and 11 demethoxyreserpiline (3), reserpiline (4), serpentine (5), ajmaline (6), ajmalicine (7), yohimbine (8), and alpha-yohimbine (9) was evaluated using microbroth dilution assay. Further, alpha-yohimbine (9) was chemically transformed into six semisynthetic derivatives (9A-9F), and their antibacterial and synergy potential in combination with nalidixic acid (NAL) against E. coli strains CA8000 and DH5alpha were also evaluated. The IA 1, 2, 4, 5, 9 and the derivative 9F showed eightfold reduction in the MIC of NAL against the DH5alpha and four- to eightfold reduction against CA8000. These alkaloids also reduced MIC of another antibiotic, tetracycline up to 8folds, against the MDREC-KG4, a multidrug-resistant clinical isolate of E. coli. Mode of action study of these alkaloids showed efflux pumps inhibitory potential, which was supported by their in silico binding affinity and downregulation of efflux pump genes. These results may be of great help in the development of cost-effective antibacterial combinations for treating patients infected with multidrug-resistant Gram negative infections. PMID- 26132413 TI - Identification and Co-complex Structure of a New S. pyogenes SpeB Small Molecule Inhibitor. AB - The secreted Streptococcus pyogenes cysteine protease SpeB is implicated in host immune system evasion and bacterial virulence. We present a small molecule inhibitor of SpeB 2477 identified from a high-throughput screen based on the hydrolysis of a fluorogenic peptide substrate Ac-AIK-AMC. 2477 inhibits other SpeB-related proteases but not human caspase-3, suggesting that the molecule targets proteases with the papain-like structural fold. A 1.59 A X-ray crystal structure of 2477 bound to the SpeB active site reveals the mechanism of inhibition and the essential constituents of 2477 necessary for binding. An assessment against a panel of 2477 derivatives confirms our structural findings and shows that a carbamate and nitrile on 2477 are required for SpeB inhibition, as these moieties provide an extensive network of electrostatic and hydrogen bonding interactions with SpeB active site residues. Surprisingly, despite 2477 having a reduced inhibitory potential against papain, the majority of 2477 related compounds inhibit papain to a much greater and broader extent than SpeB. These findings indicate that SpeB is more stringently selective than papain for this panel of small molecule inhibitors. On the basis of our structural and biochemical characterization, we propose modifications to 2477 for subsequent rounds of inhibitor design that will impart specificity to SpeB over other papain like proteases, including alterations of the compound to exploit the differences in CA protease active site pocket sizes and electrostatics. PMID- 26132411 TI - Evidence for the Use of Multiple Mechanisms by Herpes Simplex Virus-1 R7020 to Inhibit Intimal Hyperplasia. AB - Intimal hyperplasia (IH) is the primary cause of vein bypass graft failure. The smooth muscle cell (SMC) is a key element of IH as it phenotypically switches from a contractile to a synthetic state which can become pathological. R7020, which is an engineered strain of Herpes Simplex Virus-1, inhibits IH in animal models. Although it has many characteristics which make it a strong candidate for use as a prophylactic agent how it inhibits IH is not well understood. The objective of this study was to identify modes of action used by R7020 to function in blood vessels that may also contribute to its inhibition of IH. The cytopathic effect of R7020 on SMCs was determined in vitro and in a rabbit IH model. In vitro assays with R7020 infected SMCs were used to quantify the effect of dose on the release kinetics of the virus as well as the effects of R7020 on cell viability and the adhesion of peripheral blood mononuclear cells (PBMCs) to SMCs in the absence and presence of tumor necrosis factor alpha (TNF-alpha). The observed cytopathic effect, which included R7020 positive filopodia that extend from cell to cell and the formation of syncytia, suggests that R7020 remains cell associated after egress and spreads cell to cell instead of by diffusion through the extracellular fluid. This would allow the virus to rapidly infect vascular cells while evading the immune system. The directionality of the filopodia in vivo suggests that the virus preferentially travels from the media towards the intima targeting SMCs that would lead to IH. The formation of syncytia would inhibit SMC proliferation as incorporated cells are not able to multiply. It was also observed that R7020 induced the fusion of PBMCs with syncytia suggesting the virus may limit the effect of macrophages on IH. Furthermore, R7020 inhibited the proliferative effect of TNF-alpha, an inflammatory cytokine associated with increased IH. Thus, the results of this study suggest that R7020 inhibits IH through multiple mechanisms. PMID- 26132414 TI - Tubulointerstitial lesions in lupus nephritis: International multicentre study in a large cohort of patients with repeat biopsy. AB - BACKGROUND: The glomerulocentric International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification is the gold standard for the evaluation of lupus nephritis, while tubulointerstitial (TIN) parameters are often under-recognized in pathological reports. METHODS: Renal biopsies from 142 patients who underwent repeat biopsy (RB) were evaluated for the following histological parameters: (i) inflammatory interstitial infiltrates; (ii) interstitial fibrosis; (iii) tubulitis; and (iv) tubular atrophy. The inter relationships between the four TIN variables were explored by multivariate analysis. A linear mixed model was used to investigate the potential impact of TIN variables on eGFR and proteinuria at the two biopsy occasions. RESULTS: The study showed that moderate-severe lesions were not so frequent at the reference biopsy, but more extensively represented upon RB. A strong association was found between the two inflammatory indices and between those related to chronic damage, while the relationship with the ISN/RPS classification was present at RB. If class IV-G was the most related with TIN (especially at RB), the existence of primary TIN in class II patients was also confirmed. Finally, our results support the hypothesis that tubulitis is an independent predictive factor for eGFR. CONCLUSIONS: We recommend that the standard histological evaluation of SLE nephritis also includes TIN features. PMID- 26132415 TI - Highly carbonylated cellulose nanofibrous membranes utilizing maleic anhydride grafting for efficient lysozyme adsorption. AB - Construction of adsorptive materials for simple, efficient, and high-throughput adsorption of proteins is critical to meet the great demands of highly purified proteins in biotechnological and biopharmaceutical industry; however, it has proven extremely challenging. Here, we report a cost-effective strategy to create carbonyl groups surface-functionalized nanofibrous membranes under mild conditions for positively charged protein adsorption. Our approach allows maleic anhydride to in situ graft on cellulose nanofibrous membranes (CMA) to construct adsorptive membranes with large surface area and tortuous porous structure. Thereby, the resultant CMA membranes exhibited high adsorption capacity of 160 mg g(-1), fast equilibrium within 12 h, and good reversibility to lysozyme. Moreover, the dynamic adsorption was performed under low pressure-drops (750 Pa), with a relatively high saturation adsorption amount of 118 mg g(-1), which matched well with the requirements for proteins purification. Considering the excellent adsorption performance of the as-prepared adsorptive membranes, this simple and intriguing approach may pave a way for the design and development of robust and cost-effective adsorption membranes to meet the great demands for fast and efficient adsorption of positively charged proteins. PMID- 26132416 TI - Decoding and Discrimination of Chemical Cues and Signals: Avoidance of Predation and Competition during Parental Care Behavior in Sympatric Poison Frogs. AB - The evolution of chemical communication and the discrimination between evolved functions (signals) and unintentional releases (cues) are among the most challenging issues in chemical ecology. The accurate classification of inter- or intraspecific chemical communication is often puzzling. Here we report on two different communication systems triggering the same parental care behavior in the poison frog Ranitomeya variabilis. This species deposits its tadpoles and egg clutches in phytotelmata and chemically recognizes and avoids sites with both predatory conspecific and non-predatory heterospecific tadpoles (of the species Hyloxalus azureiventris). Combining chemical analyses with in-situ bioassays, we identified the molecular formulas of the chemical compounds triggering this behavior. We found that both species produce distinct chemical compound combinations, suggesting two separate communication systems. Bringing these results into an ecological context, we classify the conspecific R. variabilis compounds as chemical cues, advantageous only to the receivers (the adult frogs), not the emitters (the tadpoles). The heterospecific compounds, however, are suggested to be chemical signals (or cues evolving into signals), being advantageous to the emitters (the heterospecific tadpoles) and likely also to the receivers (the adult frogs). Due to these assumed receiver benefits, the heterospecific compounds are possibly synomones which are advantageous to both emitter and receiver - a very rare communication system between animal species, especially vertebrates. PMID- 26132417 TI - Sexual dimorphism in medulloblastoma features. AB - AIMS: Male sex is a risk factor for medulloblastoma (MB), and is also a negative predictor for clinical outcome. The aim of this study was to assess sex differences in tumour biological features and hormone receptor profiles in a cohort of MB patients. METHODS AND RESULTS: Sixty-four MBs and five normal cerebella were included in the study. Cell proliferation (Ki67), apoptosis (cleaved caspase-3) and microvessel density (CD31) were evaluated in tumours by immunohistochemistry. Tissues were analysed for oestrogen receptor (ER)alpha, ERbeta1, ERbeta2, ERbeta5 and androgen receptor (AR) expression. The results demonstrated sex-specific features in MBs, with tumours from females showing a higher apoptosis/proliferation ratio and less tumour vascularization than tumours from males. MBs were negative for ERalpha and AR, but expressed ERbeta isoforms at similar levels between the sexes. Altogether, these findings indicate that signalling mechanisms that control cell turnover and angiogenesis operate more efficiently in females than in males. The lack of sex differences in the hormone receptor profiles suggests that circulating oestrogens could be the major determinants of the sexual dimorphism observed in MB features. CONCLUSIONS: Here, we provide molecular support for epidemiological data showing sex differences in MB incidence and outcome, completely defining the hormone receptor profile of the tumours. PMID- 26132418 TI - The protective role of the Bowman-Birk protease inhibitor in soybean lunasin digestion: the effect of released peptides on colon cancer growth. AB - Lunasin is a naturally-occurring peptide demonstrating chemopreventive, antioxidant and anti-inflammatory properties. To exhibit these activities, orally ingested lunasin needs to survive proteolytic attack of digestive enzymes to reach target tissues in active form/s. Preliminary studies suggested the protective role of protease inhibitors, such as the Bowman-Birk inhibitor and Kunitz-trypsin inhibitor, against lunasin's digestion by both pepsin and pancreatin. This work describes in depth the behaviour of lunasin under conditions simulating the transit through the gastrointestinal tract in the absence or presence of soybean Bowman-Birk isoinhibitor 1 (IBB1) in both active and inactive states. By liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the remaining lunasin at the end of gastric and gastro duodenal phases was quantified. Protection against the action of pepsin was independent of the amount of IBB1 present in the analyzed samples, whereas an IBB1 dose-dependent protective effect against trypsin and chymotrypsin was observed. Peptides released from lunasin and inactive IBB1 were identified by MS/MS. The remaining lunasin and IBB1 as well as their derived peptides could be responsible for the anti-proliferative activity against colon cancer cells observed for the digests obtained at the end of simulated gastrointestinal digestion. PMID- 26132419 TI - Statin-induced coronary artery disease regression rates differ in men and women. AB - PURPOSE OF REVIEW: Whether statins are equi-efficacious in women and men continues to be debated. The potential antiatherosclerotic effects of high intensity statin therapy on coronary atheroma in women compared with men have only very recently been characterized. This review aims to summarize the evidence underlying these recent observations. RECENT FINDINGS: Coronary intravascular ultrasound (IVUS) is a highly sensitive plaque imaging tool, and serial changes of plaque burden on IVUS are known to associate with incident cardiovascular events. Study of coronary atheroma by intravascular ultrasound: effect of rosuvastatin versus atorvastatin was a randomized controlled trial employing serial IVUS to evaluate the antiatherosclerotic efficacy of high-dose rosuvastatin and atorvastatin during a 24-month study period. Study of coronary atheroma by intravascular ultrasound: effect of rosuvastatin versus atorvastatin revealed significantly greater coronary atheroma regression in women compared with men, particularly in the setting of lower achieved LDL cholesterol. Results of this analysis also identified a significant interaction between sex and type of statin used. SUMMARY: These findings support the broad use of statins, especially high-intensity statins, in women with coronary artery disease, who may in fact derive greater benefit than men. These findings also suggest the need for dedicated clinical trials involving women, supporting the notion of more personalized therapeutic strategies for tackling atherosclerotic disease. PMID- 26132420 TI - A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells. AB - When cytotoxic T lymphocytes (CTL) or natural killer (NK) cells recognize tumor cells or cells infected with intracellular pathogens, they release their cytotoxic granule content to eliminate the target cells and the intracellular pathogen. Death of the host cells and intracellular pathogens is triggered by the granule serine proteases, granzymes (Gzms), delivered into the host cell cytosol by the pore forming protein perforin (PFN) and into bacterial pathogens by the prokaryotic membrane disrupting protein granulysin (GNLY). To investigate the molecular mechanisms of target cell death mediated by the Gzms in experimental in vitro settings, protein expression and purification systems that produce high amounts of active enzymes are necessary. Mammalian secreted protein expression systems imply the potential to produce correctly folded, fully functional protein that bears posttranslational modification, such as glycosylation. Therefore, we used a cost-efficient calcium precipitation method for transient transfection of HEK293T cells with human Gzms cloned into the expression plasmid pHLsec. Gzm purification from the culture supernatant was achieved by immobilized nickel affinity chromatography using the C-terminal polyhistidine tag provided by the vector. The insertion of an enterokinase site at the N-terminus of the protein allowed the generation of active protease that was finally purified by cation exchange chromatography. The system was tested by producing high levels of cytotoxic human Gzm A, B and M and should be capable to produce virtually every enzyme in the human body in high yields. PMID- 26132421 TI - Antiproliferative Trihydroxyalkylcyclohexenones from Pleiogynium timoriense. AB - Investigation of a DCM extract of the bark of Pleiogynium timoriense from the former Merck collection of natural product extracts for antiproliferative activity indicated that it was active with an IC50 value of 1.3 MUg/mL against the A2780 ovarian cancer cell line. Bioassay-directed fractionation of this extract yielded the three new bioactive trihydroxyalkylcyclohexenones 1-3. Their structures were determined by a combination of spectroscopic and chemical methods. Compounds 1-3 exhibited submicromolar antiproliferative activity against the A2780 human ovarian cancer cell line, with IC50 values of 0.8, 0.7, and 0.8 MUM, respectively. PMID- 26132422 TI - Publication Patterns in Death Studies: 40 Years On. AB - As a living legacy to the founding editorship of Hannelore Wass, Death Studies has played a leading role in promoting scholarship in the field of thanatology for nearly 4 decades. In this article, the authors analyze publication patterns in the journal in the 25 years since Wass handed off the journal's editorial management to her successor, focusing on changing patterns of authorship, topical focus, and methodological emphasis of articles across this period. The results document the increasing feminization of the field, the impressive internationality of the research networks driving its development, and the substantial empirical foundation for major lines of research concerned with bereavement, death attitudes, and suicide. Placed against the backdrop of early trends in publication during Wass's overview, such findings suggest the maturation of research in this interdisciplinary specialty and validate her long range anticipation of the field's prospects as this flagship journal moves toward its fifth decade of publication. PMID- 26132423 TI - Effects of rapid maxillary expansion on nasal mucociliary clearance. AB - OBJECTIVE: To evaluate the changes in nasal mucociliary clearance in orthodontic patients after rapid maxillary expansion (RME) therapy. MATERIALS AND METHODS: Forty-two children (25 boys and 17 girls) participated in this study. The RME group consisted of 21 patients (mean age, 13.8 years), who had undergone RME at the initiation of orthodontic treatment. The control group consisted of 21 subjects (mean age, 13.6 years), who were attending the department of orthodontics for active orthodontic treatment. The nasal mucociliary clearance was assessed by the saccharin test. Saccharin transit times (STTs) were measured for each treated subject before expansion (T1), after RME (T2), and after a 3 month retention period (T3). Records were obtained at the same time intervals for each group. RESULTS: The STT decreased significantly in the RME group after expansion and retention (P < .05). A statistically significant difference was found when the STTs of the control and RME groups were compared after expansion and retention (P < .05). CONCLUSIONS: The STTs of young orthodontic patients with maxillary narrowness and without any history of nasal or systemic disease were within normal limits. However, RME increased the mucociliary clearance in patients who had maxillary narrowness, having positive effects on nasal physiology and increasing nasal cavity volume. PMID- 26132424 TI - Comparison of robot-assisted and laparoscopic partial nephrectomy for complex renal tumours with a RENAL nephrometry score >=7: peri-operative and oncological outcomes. AB - OBJECTIVE: To evaluate the peri-operative, functional and oncological outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for moderately or highly complex tumours (defined as RENAL nephrometry score >=7). PATIENTS AND METHODS: We retrospectively analysed the medical charts of 216 patients with complex tumours who underwent LPN (n = 135) or RAPN (n = 81) between 2008 and 2014. Peri-operative data, pathological variables, complications, functional and oncological outcomes were reviewed. RESULTS: Demographic characteristics were similar in the two groups. LPN was associated with a longer operating time (149.6 vs 135.6 min; P = 0.017) and greater estimated blood loss (220.8 vs 196.5 mL; P = 0.013). RAPN was associated with a higher direct cost. There were no differences in warm ischaemia time, transfusion rate, conversion rate, hospital stay, operative complications and estimated glomerular filtration rate change at 6 months after surgery. The mean follow-ups for LPN and RAPN were 31.4 and 16.5 months, respectively. The 3-year recurrence free survival rate was 95.2% for LPN and 97.1% for RAPN (P = 0.71). CONCLUSION: In patients with complex tumours, RAPN and LPN provided acceptable and similar results in terms of peri-operative, functional and oncological outcomes. RAPN was superior to LPN in terms of estimated blood loss and operating time, and LPN was the more cost-effective approach. Both surgery techniques remain viable options in the management of complex tumours with RENAL scores >=7. PMID- 26132425 TI - An injectable and fast-degradable poly(ethylene glycol) hydrogel fabricated via bioorthogonal strain-promoted azide-alkyne cycloaddition click chemistry. AB - Biocompatible and degradable injectable materials prepared via bioorthogonal reactions are highly promising for biomedical applications because they can be formed in situ and administered in a minimally invasive way. In this work, a PEG based injectable hydrogel was fabricated via a copper-free, strain-promoted azide alkyne cycloaddition (SPAAC) click chemistry. Azide and cyclooctyne moieties on the PEG backbones underwent a rapid click reaction to trigger the formation of the hydrogel within several minutes. Resulting from the introduction of ester groups into the cross-linked network, the hydrogel presented pH-dependent hydrolysis and biological fast degradability. Good biocompatibility of the hydrogel was verified by in vitro cytotoxicity assay and in vivo studies. The hydrogel formed in situ after subcutaneously injecting the gel precursors into Kungming (KM) mice. The implanted hydrogel caused a mild inflammatory response in vivo, and the surrounding tissues fully recovered a week after the injection. The injectable and fast-degradable hydrogel fabricated by the bioorthogonal click reaction may be useful as biomaterials such as embolic agents for interventional therapy. PMID- 26132426 TI - Endoscopes and the "Superbug" Outbreak. PMID- 26132427 TI - Effect of Leishmania spp infection on the survival, life expectancy, fecundity and fertility of Lutzomyia longipalpiss.l. and Lutzomyia pseudolongipalpis. AB - We evaluated the effects of Leishmaniaspp infection on several population parameters of Lutzomyia longipalpis sensu lato andLutzomyia pseudolongipalpis, vectors of visceral leishmaniasis in Venezuela, under experimental conditions during the first post-feeding period. Females of both species were allowed to feed and engorge on a suspension of fresh washed human red blood cells in foetal calf serum. These blood cells were either non-infected or infected with one of the fourLeishmaniaspp strains and were offered through a chicken skin membrane. The longevity, life expectancy and the fecundity of uninfected flies were similar in both species, but the fertility was significantly lower in uninfected Lu. longipalpis females. In all cases, the infection of Lu. longipalpis and Lu. pseudolongipalpis by the Leishmaniastrains resulted in significant detrimental effects, which exerted a fitness cost expressed by reduced survival and life expectancy, as well as decreased fertility and fecundity compared with the control groups. Nevertheless, differences in these parameters were observed between these vector species depending on whether they were infected with the autochthonous Venezuelan Leishmania infantum strain (NESA) or the Brazilian reference strain (PP75). The experimental data obtained agree with field data on the natural infection of these vector species and the significance of this scenario is discussed. PMID- 26132428 TI - Draft genome sequence of a multidrug-resistant Acinetobacter baumannii ST15 (CC15) isolated from Brazil. AB - Acinetobacter baumannii is an important pathogen frequently associated with nosocomial outbreaks around the world. In Brazil, A. baumannii has become particularly problematic because of its prevalence and the carbapenems resistance. Here, we report the draft genome sequence of a multidrug-resistant A. baumannii(ST15/CC15) isolated in 2009 from the state of Espirito Santo (Southeast Brazil). We observed important resistance determinant genes in an estimated genome size of 4,102,788 bp with 3,862 predicted coding regions. A detailed report of the genomic data analysis might help to understand the specific features of highly successful strains belonged to a relevant complex clonal in different Brazilian geographical regions. PMID- 26132429 TI - Detection of influenza B lineages from 2001 to 2013 in a tertiary hospital in the city of Sao Paulo, Brazil. AB - Two antigenically distinct lineages of influenza B viruses, the Victoria-like and Yamagata-like strains, currently circulate among humans. Surveillance from United States of America and Europe over the last 10 years showed that the chance of a correct matching between vaccine and the circulating lineage had been 50%. We investigated influenza B infection in different patient groups (asymptomatic, general community, with comorbidities and hospitalised) attended at a tertiary hospital in the city of Sao Paulo, Brazil between 2001-2013. All samples were screened for influenza B virus by one-step real-time reverse transcription polymerase chain reaction. From 2,992 respiratory samples collected, 114 (3.8%) tested positive for influenza B. Teenagers (13-18 years) presented the highest rate of 18.5% (odds ratio 22.87, 95% confidence interval 2.90-180.66, p < 0.001). One hundred nine samples could be characterised: 50 were Yamagata-like and 59 were Victoria-like strains. Mismatching between the vaccine and predominant circulating strain was observed in 2002 and 2013 seasons. Based on data collected during a period of 12 years, we found that influenza B was more frequent in teenagers. Co-circulation of both lineages and mismatch with the vaccine strain can occur. Our data highlighted the importance of quadrivalent vaccines and future analysis of the age groups included in vaccination programs. PMID- 26132430 TI - Development of a novel plaque reduction neutralisation test for hantavirus infection. AB - In the Americas, hantaviruses cause severe cardiopulmonary syndrome (HCPS) with a high fatality rate. Hantavirus infection is commonly diagnosed using serologic techniques and reverse transcription-polymerase chain reaction. This paper presents a novel plaque reduction neutralisation test (PRNT) for detecting antibodies to Brazilian hantavirus. Using PRNT, plaque detection was enhanced by adding 0.6% of dimethyl sulfoxide into the overlay culture medium of the infected cells. This procedure facilitated clear visualisation of small plaques under the microscope and provided for easy and accurate plaque counting. The sera from 37 HCPS patients from the city of Ribeirao Preto, Brazil was evaluated for the Rio Mamore virus (RIOMV) using PRNT. Six samples exhibited neutralising antibodies; these antibodies exhibited a low titre. The low level of seropositive samples may be due to fewer cross-reactions between two different hantavirus species; the patients were likely infected by Araraquara virus (a virus that has not been isolated) and RIOMV was used for the test. This assay offers a new approach to evaluating and measuring neutralising antibodies produced during hantavirus infections and it can be adapted to other hantaviruses, including viruses that will be isolated in the future. PMID- 26132431 TI - How Transdiagnostic Factors of Personality and Psychopathology Can Inform Clinical Assessment and Intervention. AB - Research suggests that many mental disorders-mood and anxiety, substance use, and personality psychopathology-are related through relatively few latent transdiagnostic factors. With regard to the comorbidity of personality disorders and common mental disorders, factor structures such as internalizing externalizing have been replicated in numerous samples, across the life span, and around the globe. One critical feature of transdiagnostic factors is that they serve as a point of intersection between personality and psychopathology, making them particularly relevant phenomena for applied clinical work. Although numerous studies have supported the significance of transdiagnostic factors for research and classification purposes, there has been comparatively less articulation of how such factors might be of benefit to practicing assessment clinicians. Herein, we present an overview of transdiagnostic factor research findings, and we apply these findings to the clinical topics of assessment, diagnosis, and treatment. For clinicians as well as researchers, the use of transdiagnostic constructs presents positive implications for efforts to understand, characterize, and ameliorate psychopathology-including its manifestations as personality disorder in a valid, effective, and efficient way. PMID- 26132432 TI - Review of invasive meningococcal disease during the last 40 years in Turkey. AB - Due to the lack of comprehensive surveillance data representing Turkey, the authors aimed to derive information by panoramically reviewing all articles related to invasive meningococcal disease (IMD) published in the last 40 years. The following databases were reviewed: Ulakbim (the national database), BIOSIS Previews (from 1995), Evidence-Based Medicine Reviews-Cochrane Database of Systematic Reviews (from 2005), Embase (from 1996), Ovid MEDLINE(R) (from 1946) and Journals@Ovid Full Text (2014). Twenty-seven articles, 10 published in international journals and 17 in national journals, were identified. Only two were multicenter sentinel meningitis surveillance studies. Also, 74% of IMD patients were aged 5 years or younger and the median overall case fatality rate during childhood was 18.44%. Turkey is a country where meningococcal vaccination on a national basis is recommended by WHO. A vaccination strategy for serogroups B and W135 targeting the first 5 years, covering especially the first 12 months, would be appropriate. PMID- 26132433 TI - Deep Into the Fibers! Postmortem Diffusion Tensor Imaging in Forensic Radiology. AB - PURPOSE: In traumatic brain injury, diffusion-weighted and diffusion tensor imaging of the brain are essential techniques for determining the pathology sustained and the outcome. Postmortem cross-sectional imaging is an established adjunct to forensic autopsy in death investigation. The purpose of this prospective study was to evaluate postmortem diffusion tensor imaging in forensics for its feasibility, influencing factors and correlation to the cause of death compared with autopsy. METHODS: Postmortem computed tomography, magnetic resonance imaging, and diffusion tensor imaging with fiber tracking were performed in 10 deceased subjects. The Likert scale grading of colored fractional anisotropy maps was correlated to the body temperature and intracranial pathology to assess the diagnostic feasibility of postmortem diffusion tensor imaging and fiber tracking. RESULTS: Optimal fiber tracking (>15,000 fiber tracts) was achieved with a body temperature at 10 degrees C. Likert scale grading showed no linear correlation (P > 0.7) to fiber tract counts. No statistically significant correlation between total fiber count and postmortem interval could be observed (P = 0.122). Postmortem diffusion tensor imaging and fiber tracking allowed for radiological diagnosis in cases with shearing injuries but was impaired in cases with pneumencephalon and intracerebral mass hemorrhage. CONCLUSIONS: Postmortem diffusion tensor imaging with fiber tracking provides an exceptional in situ insight "deep into the fibers" of the brain with diagnostic benefit in traumatic brain injury and axonal injuries in the assessment of the underlying cause of death, considering influencing factors for optimal imaging technique. PMID- 26132434 TI - Real-time Electrophysiology: Using Closed-loop Protocols to Probe Neuronal Dynamics and Beyond. AB - Experimental neuroscience is witnessing an increased interest in the development and application of novel and often complex, closed-loop protocols, where the stimulus applied depends in real-time on the response of the system. Recent applications range from the implementation of virtual reality systems for studying motor responses both in mice and in zebrafish, to control of seizures following cortical stroke using optogenetics. A key advantage of closed-loop techniques resides in the capability of probing higher dimensional properties that are not directly accessible or that depend on multiple variables, such as neuronal excitability and reliability, while at the same time maximizing the experimental throughput. In this contribution and in the context of cellular electrophysiology, we describe how to apply a variety of closed-loop protocols to the study of the response properties of pyramidal cortical neurons, recorded intracellularly with the patch clamp technique in acute brain slices from the somatosensory cortex of juvenile rats. As no commercially available or open source software provides all the features required for efficiently performing the experiments described here, a new software toolbox called LCG was developed, whose modular structure maximizes reuse of computer code and facilitates the implementation of novel experimental paradigms. Stimulation waveforms are specified using a compact meta-description and full experimental protocols are described in text-based configuration files. Additionally, LCG has a command-line interface that is suited for repetition of trials and automation of experimental protocols. PMID- 26132435 TI - Reduction of Iatrogenic Atrial Septal Defects with an Anterior and Inferior Transseptal Puncture Site when Operating the Cryoballoon Ablation Catheter. AB - The cryoballoon catheter ablates atrial fibrillation (AF) triggers in the left atrium (LA) and pulmonary veins (PVs) via transseptal access. The typical transseptal puncture site is the fossa ovalis (FO) - the atrial septum's thinnest section. A potentially beneficial transseptal site, for the cryoballoon, is near the inferior limbus (IL). This study examines an alternative transseptal site near the IL, which may decrease the frequency of acute iatrogenic atrial septal defect (IASD). Also, the study evaluates the acute pulmonary vein isolation (PVI) success rate utilizing the IL location. 200 patients were evaluated by retrospective chart review for acute PVI success rate with an IL transseptal site. An additional 128 IL transseptal patients were compared to 45 FO transseptal patients by performing Doppler intracardiac echocardiography (ICE) post-ablation to assess transseptal flow after removal of the transseptal sheath. After sheath removal and by Doppler ICE imaging, 42 of 128 (33%) IL transseptal patients demonstrated acute transseptal flow, while 45 of 45 (100%) FO transseptal puncture patients had acute transseptal flow. The difference in acute transseptal flow detection between FO and IL sites was statistically significant (P <0.0001). Furthermore, 186 of 200 patients (with an IL transseptal puncture) did not need additional ablation(s) and had achieved an acute PVI by a "cryoballoon only" technique. An IL transseptal puncture site for cryoballoon AF ablations is an effective location to mediate PVI at all four PVs. Additionally, an IL transseptal location can lower the incidence of acute transseptal flow by Doppler ICE when compared to the FO. Potentially, the IL transseptal site may reduce later IASD complications post-cryoballoon procedures. PMID- 26132436 TI - Self-assembling bubble carriers for oral protein delivery. AB - Successful oral delivery of therapeutic proteins such as insulin can greatly improve the quality of life of patients. This study develops a bubble carrier system by loading diethylene triamine pentaacetic acid (DTPA) dianhydride, a foaming agent (sodium bicarbonate; SBC), a surfactant (sodium dodecyl sulfate; SDS), and a protein drug (insulin) in an enteric-coated gelatin capsule. Following oral administration to diabetic rats, the intestinal fluid that has passed through the gelatin capsule saturates the mixture; concomitantly, DTPA dianhydride produces an acidic environment, while SBC decomposes to form CO2 bubbles at acidic pH. The gas bubbles grow among the surfactant molecules (SDS) owing to the expansion of the generated CO2. The walls of the CO2 bubbles consist of a self-assembled film of water that is in nanoscale and may serve as a colloidal carrier to transport insulin and DTPA. The grown gas bubbles continue to expand until they bump into the wall and burst, releasing their transported insulin, DTPA, and SDS into the mucosal layer. The released DTPA and SDS function as protease inhibitors to protect the insulin molecules as well as absorption enhancers to augment their epithelial permeability and eventual absorption into systemic circulation, exerting their hypoglycemic effects. PMID- 26132437 TI - Free Energy Landscapes of Alanine Oligopeptides in Rigid-Body and Hybrid Water Models. AB - Replica exchange molecular dynamics is used to study the effect of different rigid-body (mTIP3P, TIP4P, SPC/E) and hybrid (H1.56, H3.00) water models on the conformational free energy landscape of the alanine oligopeptides (acAnme and acA5nme), in conjunction with the CHARMM22 force field. The free energy landscape is mapped out as a function of the Ramachandran angles. In addition, various secondary structure metrics, solvation shell properties, and the number of peptide-solvent hydrogen bonds are monitored. Alanine dipeptide is found to have similar free energy landscapes in different solvent models, an insensitivity which may be due to the absence of possibilities for forming i-(i + 4) or i-(i + 3) intrapeptide hydrogen bonds. The pentapeptide, acA5nme, where there are three intrapeptide backbone hydrogen bonds, shows a conformational free energy landscape with a much greater degree of sensitivity to the choice of solvent model, though the three rigid-body water models differ only quantitatively. The pentapeptide prefers nonhelical, non-native PPII and beta-sheet populations as the solvent is changed from SPC/E to the less tetrahedral liquid (H1.56) to an LJ like liquid (H3.00). The pentapeptide conformational order metrics indicate a preference for open, solvent-exposed, non-native structures in hybrid solvent models at all temperatures of study. The possible correlations between the properties of solvent models and secondary structure preferences of alanine oligopeptides are discussed, and the competition between intrapeptide, peptide solvent, and solvent-solvent hydrogen bonding is shown to be crucial in the relative free energies of different conformers. PMID- 26132439 TI - Comment on "Fluorotechnology Is Critical to Modern Life: The FluoroCouncil Counterpoint to the Madrid Statement". PMID- 26132438 TI - EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas. AB - BACKGROUND: Squamous cell carcinomas (SCC) account for approximately 30% of non small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC. METHODS: Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro. RESULTS: EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration. CONCLUSIONS: EMX2 expression is down regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. PMID- 26132440 TI - Computational and Mass-Spectrometry-Based Workflow for the Discovery and Validation of Missing Human Proteins: Application to Chromosomes 2 and 14. AB - In the framework of the C-HPP, our Franco-Swiss consortium has adopted chromosomes 2 and 14, coding for a total of 382 missing proteins (proteins for which evidence is lacking at protein level). Over the last 4 years, the French proteomics infrastructure has collected high-quality data sets from 40 human samples, including a series of rarely studied cell lines, tissue types, and sample preparations. Here we described a step-by-step strategy based on the use of bioinformatics screening and subsequent mass spectrometry (MS)-based validation to identify what were up to now missing proteins in these data sets. Screening database search results (85,326 dat files) identified 58 of the missing proteins (36 on chromosome 2 and 22 on chromosome 14) by 83 unique peptides following the latest release of neXtProt (2014-09-19). PSMs corresponding to these peptides were thoroughly examined by applying two different MS-based criteria: peptide-level false discovery rate calculation and expert PSM quality assessment. Synthetic peptides were then produced and used to generate reference MS/MS spectra. A spectral similarity score was then calculated for each pair of reference-endogenous spectra and used as a third criterion for missing protein validation. Finally, LC-SRM assays were developed to target proteotypic peptides from four of the missing proteins detected in tissue/cell samples, which were still available and for which sample preparation could be reproduced. These LC SRM assays unambiguously detected the endogenous unique peptide for three of the proteins. For two of these, identification was confirmed by additional proteotypic peptides. We concluded that of the initial set of 58 proteins detected by the bioinformatics screen, the consecutive MS-based validation criteria led to propose the identification of 13 of these proteins (8 on chromosome 2 and 5 on chromosome 14) that passed at least two of the three MS based criteria. Thus, a rigorous step-by-step approach combining bioinformatics screening and MS-based validation assays is particularly suitable to obtain protein-level evidence for proteins previously considered as missing. All MS/MS data have been deposited in ProteomeXchange under identifier PXD002131. PMID- 26132451 TI - Cerebral Venous Sinus Thrombosis in Users of a Hormonal Vaginal Ring. AB - BACKGROUND: Oral contraceptive pills (OCPs) are a well-established precipitant of thrombosis. The local release of hormone from the vaginal ring still results in systemic administration and therefore predisposes users to increased risk of venous thrombosis. Although representing only 1% of strokes, cerebral venous sinus thrombosis is eight times more likely in women taking OCPs than in nonusers, and the incidence of cerebral venous sinus thrombosis associated with the vaginal ring is unknown but is likely to be increased. CASES: We report four cases of cerebral venous sinus thrombosis in women using hormonal vaginal rings with negative thrombophilia testing who presented to our facility over a 2-year period. Three of the four women required mechanical thrombectomy in addition to anticoagulation, but all four women recovered and were discharged home with minimal or no neurologic deficits. CONCLUSIONS: Increased recognition of the thrombogenic potential of hormonal vaginal rings may promote earlier venous imaging and result in better clinical outcomes. PMID- 26132450 TI - Deep venous thrombosis in patients with chronic spinal cord injury. AB - CONTEXT/OBJECTIVE: Deep venous thrombosis (DVT) is a well-known complication of an acute spinal cord injury (SCI). However, the prevalence of DVT in patients with chronic SCI has only been reported in a limited number of studies. The aim of our study was to examine the prevalence of DVT in patients with SCI beyond three months after injury. DESIGN: Cross-sectional study. SETTING: Rehabilitation Department at the Bydgoszcz University Hospital in Poland. PARTICIPANTS: Sixty three patients with SCI that were more than 3 months post injury. The patients, ranging in age from 13 to 65 years, consisted of 15 women and 48 men; the mean age of the patients was 32.1 years. The time from injury varied from 4 to 124 months. OUTCOME MEASURES: Clinical assessment, D-dimer and venous duplex scan. RESULTS: The venous duplex scan revealed DVT in 5 of the 63 patients. The post injury time in four of the patients varied between 4 and 5 months; one patient was 42 months post-injury. CONCLUSION: DVT occurred in patients with chronic SCI, mainly by the 6th post injury month. PMID- 26132452 TI - Severe Postcoital Bleeding From a Uterine Artery Pseudoaneurysm 4 Months After Cesarean Delivery. AB - BACKGROUND: Uterine artery pseudoaneurysm is considered a rare complication of gynecologic and obstetric procedures. The delayed diagnosis of this condition may result in life-threatening hemorrhage. CASE: A 34-year-old woman underwent an urgent cesarean delivery for labor dystocia. The procedure was complicated with hemorrhage from the uterine incision angles requiring extra hemostatic suture. She presented with secondary postpartum hemorrhage on day 14 and again with life threatening postcoital vaginal bleeding 4 months after cesarean delivery. Magnetic resonance imaging and angiography revealed a uterine artery Pseudoaneurysm, which was treated with uterine artery embolization. CONCLUSION: Uterine artery pseudoaneurysm should be considered as a differential diagnosis in patients presenting with postpartum hemorrhage, especially if bleeding is significant and recurrent, particularly after an operative delivery. The diagnosis of a pseudoaneurysm can be made by color Doppler ultrasonography, computed tomography, magnetic resonance imaging, and angiography. PMID- 26132453 TI - Gestational Trophoblastic Disease Diagnosis Delayed by the Hook Effect. AB - BACKGROUND: A "hook effect" resulting from saturation of antibodies used in pregnancy tests can occur at human chorionic gonadotropin (hCG) levels above 500,000 milliinternational units/mL, resulting in falsely negative values. CASE: A 34-year-old woman, gravida 5 para 3, presented to the emergency department after heavy bleeding. Ultrasonogram revealed a uterine mass, urine pregnancy test result was negative, and endometrial biopsy inconclusive. The patient was discharged and presented 10 days later with recurrent bleeding. Urine pregnancy test result was again negative, but serum hCG was 581 milliinternational units/mL. Serial dilution revealed an actual hCG higher than 5 million milliinternational units/mL. She was diagnosed with gestational trophoblastic disease. CONCLUSION: Awareness of the risk of a false-negative pregnancy test result when hCG levels are extremely high may prevent delayed diagnosis of gestational trophoblastic disease. PMID- 26132454 TI - Pheochromocytoma in a Pregnant Woman With Prior Traumatic Aortic Injury. AB - BACKGROUND: Pheochromocytoma, a catecholamine-producing tumor seldom encountered in pregnancy, is often heralded by nonspecific symptoms and undue mortality with delayed diagnosis. The presence of an aortic pseudoaneurysm poses a management challenge given the risk of aortic rupture amplified by hypertensive events. CASE: A 30-year-old woman, gravida 3 para 1, presented at 23 6/7 weeks of gestation with vomiting, chest pain, and severe hypertension. Investigation revealed adrenal pheochromocytoma and pseudoaneurysm at the site of a previous aortic injury. Prazosin and phenoxybenzamine achieved alpha-blockade with subsequent addition of labetalol for beta-blockade. Concerns for aortic dissection led to endovascular aortic repair at 30 2/7 weeks of gestation. A female neonate was delivered by urgent cesarean delivery for persistent postprocedure fetal bradycardia. An adrenalectomy followed with near-immediate symptom resolution. Mother and neonate remain well. CONCLUSION: The case underscores the necessity of a meticulous approach to hypertension management and the pivotal role of diligent multidisciplinary collaboration to achieve a safe outcome. PMID- 26132455 TI - Nonhemorrhagic Adrenal Infarction With Magnetic Resonance Imaging Features During Pregnancy. AB - BACKGROUND: Adrenal infarction is an infrequent cause of severe abdominal pain during pregnancy. The magnetic resonance imaging (MRI) features of adrenal infarction have not previously been thoroughly described. CASES: A 20-year-old woman, gravida 1 para 0, presented at 27 4/7 weeks of gestation with sudden-onset right upper quadrant and flank pain. A 29-year-old woman, gravida 2 para 1, presented at 17 5/7 weeks of gestation with sudden-onset right abdominal and flank pain and again at 35 5/7 weeks of gestation with sudden-onset severe left flank and upper quadrant pain. In both patients, unilateral adrenal infarction was diagnosed on contrast-enhanced computed tomography after initial nondiagnostic ultrasonography and MRI. Clinical presentation and MRI features of nonhemorrhagic adrenal infarction are described. CONCLUSION: Nonhemorrhagic adrenal infarction may be an underdiagnosed cause of acute abdominal pain during pregnancy and can be diagnosed with MRI. PMID- 26132456 TI - Accidental Trichloroacetic Acid Burn in a Gynecology Office. AB - BACKGROUND: Trichloroacetic acid is routinely used by gynecologists to treat anogenital diseases, and accidental exposure to the health care providers may result in serious burns. This case serves to raise awareness of accidental exposure of trichloroacetic acid and describes preventive, first aid, and treatment recommendations that may limit the incidence and severity of burn injury among gynecologists. CASE: A 32-year-old female gynecologist incurred a deep second-degree, 12*14-cm, work-related chemical burn by unintentionally spilling a container of approximately 20 mL of 80% trichloroacetic acid onto her right thigh during an outpatient procedure. First aid included removal of her soaked clothing, 5 minutes of soap and cold water irrigation, and liberal placement of petroleum-based ointment onto the injury site. Treatment consisted of topical silver sulfadiazine cream twice a day, coverage with silver impregnated silicone foam dressing, and a circumferential soft bandage to minimize sheer forces along the wound. A 9-month follow-up demonstrated a well healed, mildly hypopigmented, aesthetically favorable wound with return of sensation. CONCLUSION: Accidental trichloroacetic acid burns are a potential hazard in a gynecology office. Health care workers should be familiar with prevention, first aid, and appropriate treatment that often can result in acceptable long-term outcomes. PMID- 26132457 TI - Tranexamic Acid for Hyperfibrinolytic Hemorrhage During Conservative Management of Placenta Percreta. AB - BACKGROUND: Complications of conservative management of abnormal placentation in which the placenta is left in situ for resorption include secondary hemorrhage, infection, and disseminated intravascular coagulation. CASE: A 41-year old woman received conservative treatment for placenta percreta. Nine weeks after delivery, she developed gingival bleeding, easy bruising, and moderate-to-severe vaginal bleeding. Hemostasis testing established the diagnosis of isolated hyperfibrinolysis; acute disseminated intravascular coagulation was excluded. Bleeding was successfully treated using the antifibrinolytic agent tranexamic acid. Eight weeks later uncomplicated curettage was performed. CONCLUSION: Isolated hyperfibrinolysis is a potential cause of bleeding during conservative management of placenta increta and percreta. Management of this treatment approach should include hemostasis monitoring, because hyperfibrinolysis can be successfully controlled using fibrinolysis inhibitors. PMID- 26132458 TI - Ultrasound-Guided Drainage of Supralevator Hematoma in a Hemodynamically Stable Patient. AB - BACKGROUND: Paravaginal hematomas can be life-threatening. In patients with intact vaginal walls and perineum, they may pose a diagnostic and therapeutic challenge. Supralevator hematomas are much less common than infralevator hematomas. CASE: We present a case of puerperal hemorrhagic shock after a normal vaginal delivery in a low-risk parous woman resulting from an occult supralevator hematoma. Because the woman was hemodynamically unstable initially, she underwent a vaginal surgical drainage. A week later, the supravaginal hematoma reformed. At this time the patient was hemodynamically stable, and ultrasound-guided drainage was performed, which resulted in complete resolution of the hematoma within 10 days. CONCLUSION: In a clinically stable puerperal patient, ultrasound-guided drainage of a supralevator hematoma resulted in rapid and complete resolution of symptoms. PMID- 26132459 TI - Disseminated Intravascular Coagulation Complicating the Conservative Management of Placenta Percreta. AB - BACKGROUND: Retention of the placenta is an option in the management of placenta percreta; however, it may be associated with significant morbidity. CASE: We present a case of conservative management of placenta percreta. Disseminated intravascular coagulation (DIC) developed 49 days after delivery. An urgent hysterectomy was performed, followed by rapid normalization of coagulation parameters. CONCLUSION: Disseminated intravascular coagulation may complicate the conservative management of placenta percreta and can manifest weeks after delivery in the absence of antecedent hemorrhage or infection. The time course and presentation of this case are similar to the development of DIC after prolonged retention of a fetal demise with a probable shared pathophysiology. Close follow-up may facilitate prompt diagnosis of DIC, thereby minimizing associated morbidity. PMID- 26132460 TI - Design and Characterization of Phosphine Iron Hydrides: Toward Hydrogen-Producing Catalysts. AB - Diamagnetic iron chloro compounds [(P(Ph)2N(Ph)2)FeCp*Cl] [1Cl] and [(P(Cy)2N(Ph)2)FeCp*Cl] [2Cl] and the corresponding hydrido complexes [(P(Ph)2N(Ph)2)FeCp*H] [1H] and [(P(Cy)2N(Ph)2)FeCp*H] [2H] have been synthesized and characterized by NMR spectroscopy, electrochemical studies, electronic absorption, and (57)Fe Mossbauer spectroscopy (P(Ph)2N(Ph)2 = 1,3,5,7-tetraphenyl 1,5-diphospha-3,7-diazacyclooctane, P(Cy)2N(Ph)2 = 1,5-dicyclohexyl-3,7-diphenyl 1,5-diphospha-3,7-diazacyclooctane, Cp* = pentamethylcyclopentadienyl). Molecular structures of [2Cl], [1H], and [2H], derived from single-crystal X-ray diffraction, revealed that these compounds have a typical piano-stool geometry. The results show that the electronic properties of the hydrido complexes are strongly influenced by the substituents at the phosphorus donor atoms of the P(R)2N(Ph)2 ligand, whereas those of the chloro complexes are less affected. These results illustrate that the hydride is a strong-field ligand, as compared to chloride, and thus leads to a significant degree of covalent character of the iron hydride bonds. This is important in the context of possible catalytic intermediates of iron hydrido species, as proposed for the catalytic cycle of [FeFe] hydrogenases and other synthetic catalysts. Both hydrido compounds [1H] and [2H] show enhanced catalytic currents in cyclic voltammetry upon addition of the strong acid trifluoromethanesulfonimide [NHTf2] (pKa(MeCN) = 1.0). In contrast to the related complex [(P(tBu)N(Bn))2FeCp(C6F5)H], which was reported by Liu et al. (Nat. Chem. 2013, 5, 228-233) to be an electrocatalyst for hydrogen splitting, the here presented hydride complexes [1H] and [2H] show the tendency for electrocatalytic hydrogen production. Hence, the catalytic direction of this class of monoiron compounds can be reversed by specific ligand modifications. PMID- 26132461 TI - Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons. AB - Sustained enhancement of axonal signaling and increased neurotransmitter release by the activation of pre-synaptic nicotinic acetylcholine receptors (nAChRs) is an important mechanism for neuromodulation by acetylcholine (ACh). The difficulty with access to probing the signaling mechanisms within intact axons and at nerve terminals both in vitro and in vivo has limited progress in the study of the pre synaptic components of synaptic plasticity. Here we introduce a gene-chimeric preparation of ventral hippocampal (vHipp)-accumbens (nAcc) circuit in vitro that allows direct live imaging to analyze both the pre- and post-synaptic components of transmission while selectively varying the genetic profile of the pre- vs post synaptic neurons. We demonstrate that projections from vHipp microslices, as pre synaptic axonal input, form multiple, reliable glutamatergic synapses with post synaptic targets, the dispersed neurons from nAcc. The pre-synaptic localization of various subtypes of nAChRs are detected and the pre-synaptic nicotinic signaling mediated synaptic transmission are monitored by concurrent electrophysiological recording and live cell imaging. This preparation also provides an informative approach to study the pre- and post-synaptic mechanisms of glutamatergic synaptic plasticity in vitro. PMID- 26132462 TI - Multiscale reconstruction for MR fingerprinting. AB - PURPOSE: To reduce the acquisition time needed to obtain reliable parametric maps with Magnetic Resonance Fingerprinting. METHODS: An iterative-denoising algorithm is initialized by reconstructing the MRF image series at low image resolution. For subsequent iterations, the method enforces pixel-wise fidelity to the best matching dictionary template then enforces fidelity to the acquired data at slightly higher spatial resolution. After convergence, parametric maps with desirable spatial resolution are obtained through template matching of the final image series. The proposed method was evaluated on phantom and in vivo data using the highly undersampled, variable-density spiral trajectory and compared with the original MRF method. The benefits of additional sparsity constraints were also evaluated. When available, gold standard parameter maps were used to quantify the performance of each method. RESULTS: The proposed approach allowed convergence to accurate parametric maps with as few as 300 time points of acquisition, as compared to 1000 in the original MRF work. Simultaneous quantification of T1, T2, proton density (PD), and B0 field variations in the brain was achieved in vivo for a 256 * 256 matrix for a total acquisition time of 10.2 s, representing a three-fold reduction in acquisition time. CONCLUSION: The proposed iterative multiscale reconstruction reliably increases MRF acquisition speed and accuracy. Magn Reson Med 75:2481-2492, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26132463 TI - The Association of Satisfaction and Perceived Burden With Anxiety and Depression in Primary Caregivers of Dependent Elderly Relatives. AB - Some researchers have viewed caregiver burden and satisfaction as two ends of the same continuum rather than as independent aspects of the caregiving experience. We conducted a cross-sectional study of primary caregivers of dependent elderly relatives in Spain (N = 200; probabilistic sample), to determine whether satisfaction and perceived burden coexisted in caregivers, and whether these variables, considered separately and in combination, were associated with anxiety and depression, while controlling for objective aspects of care recipients' needs. Data on satisfaction with care, perceived burden, objective burden, anxiety, and depression were gathered in 2013 by interviews in caregivers' homes. Descriptive, bivariate, and multivariate analyses were performed. Of the 200 primary caregivers, 12.5% reported both high satisfaction with care and high perceived burden. Anxiety and depression levels were lower in caregivers with high satisfaction and low perceived burden than in those with low satisfaction and high burden or with high satisfaction and high burden. Our findings support the following conclusions: (1) Satisfaction may be experienced despite the presence of stressful factors; (2) the combination of high satisfaction and low burden might have protective effects on anxiety and depression in caregivers. PMID- 26132464 TI - Deep-Ultraviolet Resonance Raman (DUVRR) Spectroscopy of Therapeutic Monoclonal Antibodies Subjected to Thermal Stress. AB - The structural assessment of Rituximab, an IgG1 mAb, was investigated with deep ultraviolet resonance Raman (DUVRR) spectroscopy. DUVRR spectroscopy was used to monitor the changes to the secondary structure of Rituximab under thermal stress. DUVRR spectra showed obvious changes from 22 to 72 degrees C. Specifically, changes in the amide I vibrational mode were assigned to an increase in unordered structure (random coil). Structural changes in samples heated to 72 degrees C were related to loss in drug potency via a complement dependent cytotoxicity (CDC) bioassay. The DUVRR spectroscopic method shows promise as a tool for the quality assessment of mAb drug products and would represent an improvement over current methodology in terms of analysis time and sample preparation. To determine the scope of the method, protein pharmaceuticals of different molecular weights (ranging from 4 to 143 kDa) and secondary structure (beta-sheet, alpha helix and unordered structure) were analyzed. The model illustrated the method's sensitivity for the analysis of protein drug products of different secondary structure. Results show promise for DUVRR spectroscopy as a rapid screening tool of a variety of formulated protein pharmaceuticals. PMID- 26132467 TI - Should Symbionts Be Nice or Selfish? Antiviral Effects of Wolbachia Are Costly but Reproductive Parasitism Is Not. AB - Symbionts can have mutualistic effects that increase their host's fitness and/or parasitic effects that reduce it. Which of these strategies evolves depends in part on the balance of their costs and benefits to the symbiont. We have examined these questions in Wolbachia, a vertically transmitted endosymbiont of insects that can provide protection against viral infection and/or parasitically manipulate its hosts' reproduction. Across multiple symbiont strains we find that the parasitic phenotype of cytoplasmic incompatibility and antiviral protection are uncorrelated. Strong antiviral protection is associated with substantial reductions in other fitness-related traits, whereas no such trade-off was detected for cytoplasmic incompatibility. The reason for this difference is likely that antiviral protection requires high symbiont densities but cytoplasmic incompatibility does not. These results are important for the use of Wolbachia to block dengue virus transmission by mosquitoes, as natural selection to reduce these costs may lead to reduced symbiont density and the loss of antiviral protection. PMID- 26132465 TI - Mitral Annular and Coronary Artery Calcification Are Associated with Mortality in HIV-Infected Individuals. AB - BACKGROUND: HIV infection increases cardiovascular risk. Coronary artery calcification (CAC) and mitral annular calcification (MAC) identify patients at risk for cardiovascular disease (CVD). The purpose of this study was to examine the association between MAC, CAC and mortality in HIV-infected individuals. METHODS AND RESULTS: We studied 152 asymptomatic HIV-infected individuals with transthoracic echocardiography (TTE) and computed tomography (CT). MAC was identified on TTE using standardized criteria. Presence of CAC, CAC score and CAC percentiles were determined using the modified Agatston criteria. Mortality data was obtained from the Social Security and National Death Indices (SSDI/NDI). The median age was 49 years; 87% were male. The median duration of HIV was 16 years; 84% took antiretroviral therapy; 64% had an undetectable viral load. CVD risk factors included hypertension (35%), smoking (62%) and dyslipidemia (35%). Twenty five percent of individuals had MAC, and 42% had CAC. Over a median follow-up of 8 years, 11 subjects died. Subjects with CAC had significantly higher mortality compared to those with MAC only or no MAC. The Harrell's C-statistic of CAC was 0.66 and increased to 0.75 when MAC was added (p = 0.05). MAC, prior CVD, age and HIV viral load were independently associated with higher age- and gender-adjusted CAC percentiles in an adjusted model (p < 0.05 for all). CONCLUSION: In HIV patients, the presence of MAC, traditional risk factors and HIV viral load were independently associated with CAC. Presence of CAC and MAC may be useful in identifying HIV-infected individuals at higher risk for death. PMID- 26132468 TI - In Vivo Osteogenic Potential of Biomimetic Hydroxyapatite/Collagen Microspheres: Comparison with Injectable Cement Pastes. AB - The osteogenic capacity of biomimetic calcium deficient hydroxyapatite microspheres with and without collagen obtained by emulsification of a calcium phosphate cement paste has been evaluated in an in vivo model, and compared with an injectable calcium phosphate cement with the same composition. The materials were implanted into a 5 mm defect in the femur condyle of rabbits, and bone formation was assessed after 1 and 3 months. The histological analysis revealed that the cements presented cellular activity only in the margins of the material, whereas each one of the individual microspheres was covered with osteogenic cells. Consequently, bone ingrowth was enhanced by the microspheres, with a tenfold increase compared to the cement, which was associated to the higher accessibility for the cells provided by the macroporous network between the microspheres, and the larger surface area available for osteoconduction. No significant differences were found in terms of bone formation associated with the presence of collagen in the materials, although a more extensive erosion of the collagen-containing microspheres was observed. PMID- 26132469 TI - Evidences on the Ability of Mycorrhizal Genus Piloderma to Use Organic Nitrogen and Deliver It to Scots Pine. AB - Ectomycorrhizal (ECM) symbiosis has been proposed to link plant photosynthesis and soil organic matter (SOM) decomposition through the production of fungal enzymes which promote SOM degradation and nitrogen (N) uptake. However, laboratory and field evidence for the existence of these processes are rare. Piloderma sp., a common ECM genus in boreal forest soil, was chosen as model mycorrhiza for this study. The abundance of Piloderma sp. was studied in root tips and soil over one growing season and in winter. Protease production was measured from ectomycorrhiza and soil solution in the field and pure fungal cultures. We also tested the effect of Piloderma olivaceum on host plant organic N nutrition in the laboratory. The results showed that Piloderma sp. was highly abundant in the field and produced extracellular proteases, which correlated positively with the gross primary production, temperature and soil respiration. In the laboratory, Piloderma olivaceum could improve the ability of Pinus sylvestris L. to utilize N from extragenous proteins. We suggest that ECM fungi, although potentially retaining N in their hyphae, are important in forest C and N cycling due to their ability to access proteinaeous N. As Piloderma sp. abundance appeared to be seasonally highly variable, recycling of fungal-bound N after hyphal death may therefore be of primary importance for the N cycling in boreal ecosystems. PMID- 26132470 TI - The sequence of prenatal growth restraint and post-natal catch-up growth leads to a thicker intima-media and more pre-peritoneal and hepatic fat by age 3-6 years. AB - BACKGROUND: Infants born small-for-gestational-age (SGA) who develop post-natal weight catch-up are at risk for insulin resistance, central adiposity and cardiovascular disease in later life, even in the absence of overweight. OBJECTIVE: In young (age 3-6 years) non-obese SGA children, we assessed arterial health (as judged by intima-media thickness [IMT]) and abdominal fat distribution (subcutaneous, visceral, preperitoneal and hepatic components by magnetic resonance imaging [MRI] and/or ultrasound [US]) besides a selection of endocrine markers. METHODS: Comparisons of measures in SGA (n = 27) vs. appropriate-for-GA (AGA) children (n = 19) of similar height, weight and body mass index. Longitudinal outcomes (age 3-6 years) were carotid IMT (cIMT); fasting glucose, circulating insulin, IGF-I and high-molecular-weight (HMW) adiponectin; abdominal fat partitioning by US. Cross-sectional outcomes (age 6 years) were aortic IMT (aIMT) and abdominal fat partitioning by MRI. RESULTS: At 3 and 6 years, cIMT and IGF-I results were higher and HMW adiponectin lower in SGA than AGA children; at 6 years, SGA subjects had also a thicker aIMT and more pre-peritoneal and hepatic fat, and were less insulin sensitive (all P values between <0.05 and <0.0001). cIMT correlated positively with pre-peritoneal fat, particularly at 6 years. Post SGA status and weight gain in early childhood (between 3 and 6 years) were independent predictors of cIMT at 6 years, explaining 48 % of its variance. CONCLUSION: SGA children aged 3-6 years were found to have a thicker intima- media and more pre-peritoneal and hepatic fat than AGA children of comparable size. PMID- 26132471 TI - Transcription factors that interact with p53 and Mdm2. AB - The tumor suppressor p53 is activated upon cellular stresses such as DNA damage, oncogene activation, hypoxia, which transactivates sets of genes that induce DNA repair, cell cycle arrest, apoptosis, or autophagy, playing crucial roles in the prevention of tumor formation. The central regulator of the p53 pathway is Mdm2 which inhibits transcriptional activity, nuclear localization and protein stability. More than 30 cellular p53-binding proteins have been isolated and characterized including Mdm2, Mdm4, p300, BRCA1/2, ATM, ABL and 53BP-1/2. Most of them are nuclear proteins; however, not much is known about p53-binding transcription factors. In this review, we focus on transcription factors that directly interact with p53/Mdm2 through direct binding including Dmp1, E2F1, YB-1 and YY1. Dmp1 and YB-1 bind only to p53 while E2F1 and YY1 bind to both p53 and Mdm2. Dmp1 has been shown to bind to p53 and block all the known functions for Mdm2 on p53 inhibition, providing a secondary mechanism for tumor suppression in Arf-null cells. Although E2F1-p53 binding provides a checkpoint mechanism to silence hyperactive E2F1, YB-1 or YY1 interaction with p53 subverts the activity of p53, contributing to cell cycle progression and tumorigenesis. Thus, the modes and consequences for each protein-protein interaction vary from the viewpoint of tumor development and suppression. PMID- 26132472 TI - Beyond Gene Inactivation: Evolution of Tools for Analysis of Serotonergic Circuitry. AB - In the brain, serotonin (5-hydroxytryptamine, 5-HT) controls a multitude of physiological and behavioral functions. Serotonergic neurons in the raphe nuclei give rise to a complex and extensive network of axonal projections throughout the whole brain. A major challenge in the analysis of these circuits is to understand how the serotonergic networks are linked to the numerous functions of this neurotransmitter. In the past, many studies employed approaches to inactivate different genes involved in serotonergic neuron formation, 5-HT transmission, or 5-HT metabolism. Although these approaches have contributed significantly to our understanding of serotonergic circuits, they usually result in life-long gene inactivation. As a consequence, compensatory changes in serotonergic and other neurotransmitter systems may occur and complicate the interpretation of the observed phenotypes. To dissect the complexity of the serotonergic system with greater precision, approaches to reversibly manipulate subpopulations of serotonergic neurons are required. In this review, we summarize findings on genetic animal models that enable control of 5-HT neuronal activity or mapping of the serotonergic system. This includes a comparative analysis of several mouse and rat lines expressing Cre or Flp recombinases under Tph2, Sert, or Pet1 promoters with a focus on specificity and recombination efficiency. We further introduce applications for Cre-mediated cell-type specific gene expression to optimize spatial and temporal precision for the manipulation of serotonergic neurons. Finally, we discuss other temporally regulated systems, such as optogenetics and designer receptors exclusively activated by designer drugs (DREADD) approaches to control 5-HT neuron activity. PMID- 26132473 TI - The relationship between the Rat Grimace Scale and mechanical hypersensitivity testing in three experimental pain models. AB - BACKGROUND: The assessment of facial expressions associated with pain has been used to evaluate pain in humans and has recently found application in non-human mammals. These so called 'grimace scales' have the potential to be developed into a widely accepted non-invasive method of measuring pain in laboratory rodents. Currently, common methodologies to assess pain rely on nociceptive tests that assess stimulus evoked withdrawal responses. These tests, however, are limited to the assessment of a reflexive response without an affective component. This study aimed to use the recently developed Rat Grimace Scale (RGS) and assess its relationship with a conventional nociceptive test (the application of von Frey filaments). METHODS: Fifty-two adult, male Wistar rats were randomized to one of five treatment groups: intraplantar carrageenan, intraplantar complete Freund's adjuvant (CFA), plantar incision, anaesthetic control and saline injection control. The RGS and response to mechanical hypersensitivity testing was evaluated at predetermined time points before and after treatment until withdrawal responses returned to baseline levels. RESULTS: The RGS score significantly increased in all pain models. The peak RGS score also coincided with the development of paw hypersensitivity. However, mechanical hypersensitivity persisted after RGS scores returned to baseline. CONCLUSION: This study confirms that the three pain models induce pain in rodents and showed that peak pain coincided with peak mechanical hypersensitivity. However, mechanical hypersensitivity remained once pain subsided, mimicking the human experience of CFA injection. These findings further our understanding of the roles of, and relationship between, these assays in the assessment of nociception and pain. PMID- 26132474 TI - Accessible Transportation, Geographic Elevation, and Masticatory Ability Among Elderly Residents of a Rural Area. AB - Given that public transportation networks are often worse in rural areas than in urban areas, rural residents who do not drive can find it difficult to access health-promoting goods, services, and resources related to masticatory ability. Moreover, geographical location, assessed by elevation, could modify this association. The aim of this study was to test whether the association between access to transportation and masticatory ability varied by elevation. Data were collected from a cross-sectional study conducted in Mizuho and Iwami counties, Japan. Objective masticatory ability was evaluated using a test gummy jelly and elevation was estimated by the geographic information systems according to the participant's address. After excluding subjects with missing data, 672 subjects (Mizuho = 401 and Iwami = 271) were analyzed. After adjustment for potential confounders, being a driver was not significantly associated with masticatory ability among elderly people living at low elevation (<=313 m) in Mizuho county. However, after the same adjustment, being a driver remained significantly associated with increased masticatory ability among elderly at high elevations. Similar findings were observed in Iwami county. Accessible transportation was significantly associated with increased mastication ability in elderly people living at high elevations, but not in those living at low elevations. PMID- 26132475 TI - Accessibility of Catering Service Venues and Adolescent Drinking in Beijing, China. AB - This study assessed the association between accessibility of catering service venues and adolescents' alcohol use over the previous 30 days. The data were collected from cross-sectional surveys conducted in 2014, 2223 students at 27 high schools in Chaoyang and Xicheng districts, Beijing using self-administered questionnaires to collect the adolescents information on socio-demographic characteristics and recent alcohol experiences. The accessibility of, and proximity to, catering service venues were summarized by weights, which were calculated by multiplication of the type-weight and the distance-weight. All sampled schools were categorized into three subgroups (low, middle, and high geographic density) based on the tertile of nearby catering service venues, and a multi-level logistic regression analysis was performed to explore variance between the school levels. Considering the setting characteristics, the catering service venues weighted value was found to account for 8.6% of the school level variance of adolescent alcohol use. The odds ratios (OR) and 95% confidence intervals (CI) of drinking over the past 30-days among adolescents with medium and high accessibility of catering service venues were 1.17 (0.86, 1.57) and 1.47 (1.06, 2.02), respectively (p < 0.001 for trend test). This study addressed a gap in the adolescent drinking influence by the catering service venues around schools in China. Results suggest that the greater accessibility of catering service venues around schools is associated with a growing risk of recent drinking. PMID- 26132476 TI - The Construction and Validation of the Heat Vulnerability Index, a Review. AB - The occurrence of extreme heat and its adverse effects will be exacerbated with the trend of global warming. An increasing number of researchers have been working on aggregating multiple heat-related indicators to create composite indices for heat vulnerability assessments and have visualized the vulnerability through geographic information systems to provide references for reducing the adverse effects of extreme heat more effectively. This review includes 15 studies concerning heat vulnerability assessment. We have studied the indicators utilized and the methods adopted in these studies for the construction of the heat vulnerability index (HVI) and then further reviewed some of the studies that validated the HVI. We concluded that the HVI is useful for targeting the intervention of heat risk, and that heat-related health outcomes could be used to validate and optimize the HVI. In the future, more studies should be conducted to provide references for the selection of heat-related indicators and the determination of weight values of these indicators in the development of the HVI. Studies concerning the application of the HVI are also needed. PMID- 26132477 TI - The Prefrontal Cortex Activity and Psychological Effects of Viewing Forest Landscapes in Autumn Season. AB - Recently reported research indicate that forest environments have physiological and psychological relaxing effects compared to urban environments. However, some researchers claim that the stress of the subjects from being watched by others during measurements can affect the measurement result in urban experiments conducted in the center of a street. The present study was conducted to determine whether forest environments have physiological and psychological relaxing effects, using comparison of viewing a forest area with viewing an urban area from the roof of an urban building without being watched by others. Near-infrared spectroscopy (NIRS) measurement was performed on subjects while they viewed scenery for 15 min at each experimental site (urban and forest areas). Subjective assessments were performed after the NIRS measurement was complete. Total hemoglobin and oxyhemoglobin concentrations were significantly lower in the forest area than in the urban area. For semantic differential in subjective assessments, feelings of "comfortable", "natural", and "soothed" were significantly higher in the forest area than in the urban area, and for profile of mood states, negative emotions were significantly lower in the forest area than in the urban area. The results of physiological and psychological measurements show that viewing the forest enabled effective relaxation. PMID- 26132478 TI - Arsenic Accumulation and Translocation in Mangrove (Aegiceras corniculatum L.) Grown in Arsenic Contaminated Soils. AB - Mangrove wetlands serve as both a sink and source for arsenic (As), as mangrove plants are able to uptake and accumulate As. The present study used pot experiments to evaluate As accumulation and translocation in mangrove (Aegiceras corniculatum L.) seedlings grown in As contaminated soils. Results indicated that A. corniculatum seedlings grew normally under As stress with minute growth inhibition and biomass reduction at different As treatment concentrations in a range of 0-150 mg.kg(-1). As concentrations in roots, stems and leaves were increased with increasing As treatment concentrations, but As accumulated mainly in roots, with accumulation rates of 74.54%-89.26% of the total As accumulation. In particular, relatively high bioconcentration factor (BCF) in root (2.12-1.79), low BCF in stem (0.44-0.14) and leaf (0.06-0.01), and thereby a low translocation factor (TF) in stem/root (0.21-0.08) and leaf/root (0.02-0.008) were observed. These results demonstrated that A. corniculatum is an As excluder with the innate capacity to tolerate As stress and root tissues may be employed as a bio indicator of As in polluted sediments. Additionally, A. corniculatum is a potential candidate mangrove species for As phytostabilization in tropical and subtropical estuarine wetlands. PMID- 26132479 TI - Scrub Typhus Incidence Modeling with Meteorological Factors in South Korea. AB - Since its recurrence in 1986, scrub typhus has been occurring annually and it is considered as one of the most prevalent diseases in Korea. Scrub typhus is a 3rd grade nationally notifiable disease that has greatly increased in Korea since 2000. The objective of this study is to construct a disease incidence model for prediction and quantification of the incidences of scrub typhus. Using data from 2001 to 2010, the incidence Artificial Neural Network (ANN) model, which considers the time-lag between scrub typhus and minimum temperature, precipitation and average wind speed based on the Granger causality and spectral analysis, is constructed and tested for 2011 to 2012. Results show reliable simulation of scrub typhus incidences with selected predictors, and indicate that the seasonality in meteorological data should be considered. PMID- 26132480 TI - The Significance of Experiences of Nature for People with Parkinson's Disease, with Special Focus on Freezing of Gait--The Necessity for a Biophilic Environment. A Multi-Method Single Subject Study. AB - Freezing of Gait (FOG) is a common condition in people with Parkinson's disease (PD). FOG entails suddenly experiencing difficulties moving or feeling that one's feet are as glued to the ground. It is triggered, e.g., when passing through doorways. Earlier studies suggest that being in natural environments affects FOG in a positive way. Five subjects were recruited to serve as five single subject cases. We used interviews, observations, questionnaires and collected gait pattern data with aid of an accelerometer. A special designed outdoor setting was used, where we investigated whether passing through hedge openings with or without built elements triggered FOG. We found that no one experienced a FOG reaction when they passed through hedge openings without built elements. However, FOG was triggered when a doorframe was inserted into a hedge opening, and/or when peripheral vision was blocked. We interpret the results such that the doorframe triggered a phobic reflex, causing a freezing reaction. Passing through hedge openings does not trigger FOG, which we interpret as a biophilic reaction. Our results, if repeated in future studies, may have significance to everyday lives of PD patients, who could get a simpler life by consciously prioritizing stays in natural surroundings. PMID- 26132481 TI - Removal Efficiency of Faecal Indicator Organisms, Nutrients and Heavy Metals from a Peri-Urban Wastewater Treatment Plant in Thohoyandou, Limpopo Province, South Africa. AB - Wastewater treatment facilities are known sources of fresh water pollution. This study was carried out from January to June 2014 to assess the reduction efficiency of some selected contaminants in the Thohoyandou wastewater treatment plant (WWTP). The pH and electrical conductivity of the effluent fell within the South African wastewater discharge guidelines. The WWTP showed the chemical oxygen demand reduction efficiency required by the Department of Water Affairs (DWA) guidelines of 75 mg/L for the months of April and June, although it was below this standard in March and May. Free chlorine concentration varied between 0.26-0.96 mg/L and exceeded the DWA guideline value of 0.25 mg/L. The concentration of nitrate-nitrogen (NO3(-) N) in the influent and effluent varied between 0.499-2.31 mg/L and 7.545-19.413 mg/L, respectively. The concentration of NO3- N in the effluent complied with DWA effluent discharge standard of 15 mg/L, except in April and May. Phosphate concentrations in the influent and effluent were in the ranges of 0.552-42.646 mg/L and 1.572-32.554 mg/L, respectively. The WWTP showed reduction efficiencies of E. coli and Enterococci during some sampling periods but the level found in the effluent exceeded the recommended guideline value of 1000 cfu/100 mL for faecal indicator organisms in wastewater effluents. Consistent removal efficiencies were observed for Al (32-74%), Fe (7 32%) and Zn (24-94%) in most of the sampling months. In conclusion, the Thohoyandou WWTP is inefficient in treating wastewater to the acceptable quality before discharge. PMID- 26132482 TI - A Longitudinal Twin Study of Insomnia Symptoms in Adults. AB - OBJECTIVE: Twin modeling was used to conduct a genetically informative longitudinal analysis of insomnia symptoms in both sexes. METHOD: Data from the Virginia Adult Twin Studies of Psychiatric and Substance Use Disorders (n = 7,500) were used. Past-month insomnia symptoms were assessed at two time points with the shortened version of the Symptom Checklist-90. A composite score for the insomnia items (trouble falling asleep, restless or disturbed sleep, early morning awakenings) was computed. Twin modeling on the composite score was conducted in OpenMx to decompose the phenotypic variance, to examine the longitudinal stability of etiologic influences on insomnia symptoms, and to test for sex differences. RESULTS: Insomnia symptoms were most commonly endorsed at a mild severity level (composite score mean = 2.24, standard deviation = 2.51). There was no evidence for sex effects in either of the univariate models, and insomnia symptoms were found to be modestly heritable (~25% at Time 1 and ~22% at Time 2). In the longitudinal measurement model, which accounts for error of measurement, the heritability for the latent factor of insomnia symptoms increased substantially, and demonstrated quantitative sex differences. The heritability of the latent insomnia factor was ~59% in females and ~38% in males. CONCLUSIONS: Genetic factors influence insomnia symptoms in adults, moreso for females than males, and these influences are largely stable over time. When taking into account measurement error, heritability estimates are substantial, but unique environmental factors continue to account for a large amount of variance in insomnia symptoms. PMID- 26132483 TI - Corrigendum: Biomineralization mediated by anaerobic methane-consuming cell consortia. PMID- 26132488 TI - Relationship between dual task walking, cognition, and depression in oldest old people. AB - BACKGROUND: The purpose of the study was to investigate the relationship between dual task walking, cognition, and depression in oldest old people living in the community. METHODS: We conducted an observational cross-sectional study at Federal University of Sao Carlos (Brazil). We assessed 67 community-dwelling older adults aged 80 years and over, who were able to walk alone and did not present with a risk of dementia (assessed by Mini-Mental State Examination, MMSE). The assessment consisted of anamnesis, dual task using the Timed Up and Go test associated with a motor task (TUGT-motor) and a cognitive task (TUGT cognitive); cognitive measures using MMSE, Montreal Cognitive Assessment (MoCA), Clock Drawing test (CDT) and verbal fluency, and depressive measures by the Geriatric Depression Scale (GDS). RESULTS: There was a correlation with higher magnitude between cognitive tests and TUGT-cognitive, compared to TUGT-motor. For TUGT-motor, the highest correlations with cognitive tests were found between time and MMSE, MoCA (total score), and MoCA visuospatial/executive domain. For TUGT cognitive, the highest correlations with cognitive tests were between number of steps and MMSE and between time and MMSE. GDS showed a significant weak correlation with number of steps taken in TUGT-motor, wrong words, and correct/time of TUGT-cognitive. CONCLUSIONS: Dual task performances are associated with cognition in oldest old. Furthermore, dual task tests have less influence of educational level, are functional, fast, and easily applicable in clinical practice. Future studies are needed to confirm if dual task test is useful for cognitive screening in oldest old. PMID- 26132489 TI - Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption. AB - The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis. PMID- 26132490 TI - Chinese Herbal Preparation Xuebijing Potently Inhibits Inflammasome Activation in Hepatocytes and Ameliorates Mouse Liver Ischemia-Reperfusion Injury. AB - The Chinese herb preparation Xuebijing injection (XBJ) has been widely used in the management of various septic disorders or inflammation-related conditions, however the molecular mechanism of its anti-inflammatory effect remains largely elusive. In the current study, we found that XBJ treatment potently ameliorated mouse hepatic ischemia-reperfusion (IR) injury, manifested as decreased liver function tests (LDH, ALT, AST), improved inflammation and less hepatocyte apoptosis. Notably, XBJ markedly inhibited inflammasome activation and IL-1 production in mouse livers subjected to IRI, even in the absence of Kupffer cells, suggesting Kupffer cells are not necessary for hepatic inflammasome activation upon Redox-induced sterile inflammation. This finding led us to investigate the role of XBJ on hepatocyte apoptosis and inflammasome activation using an in vitro hydrogen peroxide (H2O2)-triggered hepatocyte injury model. Our data clearly demonstrated that XBJ potently inhibited apoptosis, as well as caspase-1 cleavage and IL-1beta production in a time- and dose-dependent manner in isolated hepatocytes, suggesting that in addition to its known modulatory effect on NF-kappaB-dependent inflammatory gene expression, it also has a direct impact on hepatocyte inflammasome activation. The current study not only deepens our understanding of how XBJ ameliorates inflammation and apoptosis, but also has immediate practical significance in many clinical situations such as partial hepatectomy, liver transplantation, etc. PMID- 26132491 TI - Social and Environmental Impacts of Forest Management Certification in Indonesia. AB - In response to unsustainable timber production in tropical forest concessions, voluntary forest management certification programs such as the Forest Stewardship Council (FSC) have been introduced to improve environmental, social, and economic performance over existing management practices. However, despite the proliferation of forest certification over the past two decades, few studies have evaluated its effectiveness. Using temporally and spatially explicit village level data on environmental and socio-economic indicators in Kalimantan (Indonesia), we evaluate the performance of the FSC-certified timber concessions compared to non-certified logging concessions. Employing triple difference matching estimators, we find that between 2000 and 2008 FSC reduced aggregate deforestation by 5 percentage points and the incidence of air pollution by 31%. It had no statistically significant impacts on fire incidence or core areas, but increased forest perforation by 4 km2 on average. In addition, we find that FSC reduced firewood dependence (by 33%), respiratory infections (by 32%) and malnutrition (by 1 person) on average. By conducting a rigorous statistical evaluation of FSC certification in a biodiversity hotspot such as Indonesia, we provide a reference point and offer methodological and data lessons that could aid the design of ongoing and future evaluations of a potentially critical conservation policy. PMID- 26132492 TI - Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via beta3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia. AB - Chronic intermittent hypoxia (IH) induces activation of the sympathoadrenal system, which plays a pivotal role in attenuating hypoxic pulmonary vasoconstriction (HPV) via central beta1-adrenergic receptors (AR) (brain) and peripheral beta2AR (pulmonary arteries). Prolonged hypercatecholemia has been shown to upregulate beta3AR. However, the relationship between IH and beta3AR in the modification of HPV is unknown. It has been observed that chronic stimulation of beta3AR upregulates inducible nitric oxide synthase (iNOS) in cardiomyocytes and that IH exposure causes expression of iNOS in RAW264.7 macrophages. iNOS has been shown to have the ability to dilate pulmonary vessels. Hence, we hypothesized that chronic IH activates beta3AR/iNOS signaling in pulmonary macrophages, leading to the promotion of NO secretion and attenuated HPV. Sprague Dawley rats were exposed to IH (3-min periods of 4-21% O2) for 8 h/d for 6 weeks. The urinary catecholamine concentrations of IH rats were high compared with those of controls, indicating activation of the sympathoadrenal system following chronic IH. Interestingly, chronic IH induced the migration of circulating monocytes into the lungs and the predominant increase in the number of pro inflammatory pulmonary macrophages. In these macrophages, both beta3AR and iNOS were upregulated and stimulation of the beta3AR/iNOS pathway in vitro caused them to promote NO secretion. Furthermore, in vivo synchrotron radiation microangiography showed that HPV was significantly attenuated in IH rats and the attenuated HPV was fully restored by blockade of beta3AR/iNOS pathway or depletion of pulmonary macrophages. These results suggest that circulating monocyte-derived pulmonary macrophages attenuate HPV via activation of beta3AR/iNOS signaling in chronic IH. PMID- 26132493 TI - Dispersal Timing: Emigration of Insects Living in Patchy Environments. AB - Dispersal is a life-history trait affecting dynamics and persistence of populations; it evolves under various known selective pressures. Theoretical studies on dispersal typically assume 'natal dispersal', where individuals emigrate right after birth. But emigration may also occur during a later moment within a reproductive season ('breeding dispersal'). For example, some female butterflies first deposit eggs in their natal patch before migrating to other site(s) to continue egg-laying there. How breeding compared to natal dispersal influences the evolution of dispersal has not been explored. To close this gap we used an individual-based simulation approach to analyze (i) the evolution of timing of breeding dispersal in annual organisms, (ii) its influence on dispersal (compared to natal dispersal). Furthermore, we tested (iii) its performance in direct evolutionary contest with individuals following a natal dispersal strategy. Our results show that evolution should typically result in lower dispersal under breeding dispersal, especially when costs of dispersal are low and population size is small. By distributing offspring evenly across two patches, breeding dispersal allows reducing direct sibling competition in the next generation whereas natal dispersal can only reduce trans-generational kin competition by producing highly dispersive offspring in each generation. The added benefit of breeding dispersal is most prominent in patches with small population sizes. Finally, the evolutionary contests show that a breeding dispersal strategy would universally out-compete natal dispersal. PMID- 26132494 TI - Frequency and characteristics of circulating CD4(+) CD28(null) T cells in patients with psoriasis. AB - BACKGROUND: Psoriasis is a chronic inflammatory disease that affects the skin. CD4(+) CD28(null) cells are a subset of T lymphocytes associated with systemic inflammation and increased cardiovascular disease risk, and may be involved in the pathogenesis of psoriasis. OBJECTIVES: To study the features of circulating CD4(+) CD28(null) cells in patients with psoriasis, adjusted for the influence of known cardiovascular disease risk factors. METHODS: Forty-two patients with psoriasis and 42 controls entered the study. Peripheral blood mononuclear cells were analysed for the frequency of CD4(+) CD28(null) T lymphocytes and their expression of cytotoxic granules and homing receptors. Immunostaining for cutaneous cytotoxic granules was assessed in skin biopsies from 11 patients. RESULTS: There were no differences in the frequency of CD4(+) CD28(null) T cells between groups in all situations analysed. However, there was an increased number of cells expressing cytotoxic granules and a decreased number expressing CXCR3 in ex vivo samples of patients with psoriasis. A negative correlation was observed between the frequency of ex vivo CD4(+) CD28(null) cells and psoriasis severity. After clinical remission in nine patients, ex vivo CD4(+) CD28(null) lymphocytes expressing cytotoxic granules decreased. Perforin-, granzyme B- and granulysin containing cells were found in skin lesions. Patients with psoriasis also had increased plasma levels of C-reactive protein. CONCLUSIONS: These data suggest that cytotoxic cells, such as CD4(+) CD28(null) lymphocytes, within an inflammatory environment may play a role in the pathogenesis of psoriasis. PMID- 26132495 TI - Induction and nosocomial dissemination of carbapenem and polymyxin-resistant Klebsiella pneumoniae. AB - INTRODUCTION: Polymyxins are antimicrobial agents capable of controlling carbapenemase-producing Klebsiella pneumoniae infection. METHODS: We report a cluster of four patients colonized or infected by polymyxin-resistant and Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. RESULTS: Three patients were hospitalized in adjacent wards, and two were admitted to the intensive care unit. The index case maintained prolonged intestinal colonization by KPC-producing K. pneumoniae. Three patients received polymyxin B before the isolation of polymyxin-resistant K. pneumoniae. CONCLUSIONS: Colonization by KPC producing K. pneumoniae and previous use of polymyxin B may be causally related to the development of polymyxin-resistant microorganisms. PMID- 26132496 TI - First report of Rhodnius montenegrensis (Hemiptera, Reduviidae, Triatominae) in the State of Acre, Brazil. AB - INTRODUCTION: This paper reports, for the first time, the presence of Rhodnius montenegrensis in the State of Acre, Brazil. METHODS: Two female R. montenegrensis were collected in a dwelling in the rural area of Rio Branco, Acre, Brazil. RESULTS: The occurrence of this species was confirmed, and the number of Triatominae species in the State of Acre increased from four to five. CONCLUSIONS: Further studies should be performed to reach a clearer understanding of the ecology of this arthropod, its possible role in transmitting Chagas' disease and rangeliosis, and its current geographical distribution in the region. PMID- 26132497 TI - Description of continuous data using bar graphs: a misleading approach. AB - INTRODUCTION: With the ease provided by current computational programs, medical and scientific journals use bar graphs to describe continuous data. METHODS: This manuscript discusses the inadequacy of bars graphs to present continuous data. RESULTS: Simulated data show that box plots and dot plots are more-feasible tools to describe continuous data. CONCLUSIONS: These plots are preferred to represent continuous variables since they effectively describe the range, shape, and variability of observations and clearly identify outliers. By contrast, bar graphs address only measures of central tendency. Bar graphs should be used only to describe qualitative data. PMID- 26132498 TI - Prevalence of zoonotic visceral leishmaniasis in dogs in an endemic area of Brazil. AB - INTRODUCTION: The northeast region of Brazil is endemic for zoonotic visceral leishmaniasis (ZVL). The aim of this study was to determine the prevalence of infection in dogs in Petrolina. METHODS: Blood samples were collected from dogs (n = 600), and bone-marrow biopsy was performed in animals with positive serological test results that presented clinical signs of ZVL. The serological analyses were performed using an enzyme-linked immunosorbent assay (ELISA) (S7(r)Biogene). RESULTS: Of the 600 dogs tested, 19% (115/600) presented anti-L. infantum chagasi antibodies. CONCLUSIONS: Our data are important because canine infection is an important risk factor for the human disease. PMID- 26132499 TI - Hepatitis E virus infection in Brazil: results of laboratory-based surveillance from 1998 to 2013. AB - INTRODUCTION: Data on hepatitis E virus (HEV) in Brazil are limited. We analyzed 15 years of HEV surveillance data in a major clinical laboratory in Sao Paulo, Brazil. METHODS: The seroprevalence of HEV of 2,271 patients subjected to anti HEV tests from 1998 to 2013 were analyzed. RESULTS: HEV seroprevalence was 2.1%, and the anti-HEV IgM positivity rate was 4.9%. Six hepatitis E patients were identified. CONCLUSIONS: HEV seroprevalence and detection rates appear to have increased in recent years. Hepatitis E should be investigated further and included in the differential diagnosis of hepatitis in Brazil. PMID- 26132500 TI - Analyzing Mixing Inhomogeneity in a Microfluidic Device by Microscale Schlieren Technique. AB - In this paper, we introduce the use of microscale schlieren technique to measure mixing inhomogeneity in a microfluidic device. The microscale schlieren system is constructed from a Hoffman modulation contrast microscope, which provides easy access to the rear focal plane of the objective lens, by removing the slit plate and replacing the modulator with a knife-edge. The working principle of microscale schlieren technique relies on detecting light deflection caused by variation of refractive index. The deflected light either escapes or is obstructed by the knife-edge to produce a bright or a dark band, respectively. If the refractive index of the mixture varies linearly with its composition, the local change in light intensity in the image plane is proportional to the concentration gradient normal to the optical axis. The micro-schlieren image gives a two-dimensional projection of the disturbed light produced by three dimensional inhomogeneity. To accomplish quantitative analysis, we describe a calibration procedure that mixes two fluids in a T-microchannel. We carry out a numerical simulation to obtain the concentration gradient in the T-microchannel that correlates closely with the corresponding micro-schlieren image. By comparison, a relationship between the grayscale readouts of the micro-schlieren image and the concentration gradients presented in a microfluidic device is established. Using this relationship, we are able to analyze the mixing inhomogeneity from associate micro-schlieren image and demonstrate the capability of microscale schlieren technique with measurements in a microfluidic oscillator(4). For optically transparent fluids, microscale schlieren technique is an attractive diagnostic tool to provide instantaneous full-field information that retains the three-dimensional features of the mixing process. PMID- 26132501 TI - Thromboelastography (TEG(r)) compared with total platelet count in thrombocytopenia haematological malignancy patients with bleeding: a pilot observational study. AB - BACKGROUND: There has been no reported use of Thromboelastography((r)) (TEG((r)) ) in assessing thrombocytopenic haematological malignancy (HM) patients experiencing bleeding. OBJECTIVES: To assess whether there are differences in TEG((r)) variables in thrombocytopenic HM patients experiencing clinically significant bleeding compared with those not experiencing bleeding. METHODS: Thirty adult patients with HM and a total platelet count (TPC) of <= 30 * 10(9) L(-1) were observed for greater than or equal to grade two World Health Organisation (WHO) bleeding episodes for 72 h. They had TPC, TEG((r)) parameters [maximal amplitude (MA), reaction time (R-time), alpha (alpha-angle) and functional fibrinogen (FF) levels], activated partial thromboplastin time (APTT) and prothrombin time (PT) measured at inclusion, 24 and 48 h. RESULTS: Five patients had nine significant bleeding episodes. Patients bleeding (n) were all more hypocoaguable when measured by TEG((r)) than patients not bleeding at inclusion n = 4 (MA: 16.9 vs 31.8 mm, P < 0.01; R-time: 10.1 vs 7.5 min, P = 0.02; alpha-angle: 18.8 vs 28.4, P < 0.01; FF: 182.4 vs 204 mg dL(-1), P < 0.01), at 24 h n = 3 (MA 18 vs 29.4 mm, P = 0.02; R-time: 9.4 vs 7.4 mins, P = 0.02; alpha-angle: 21.6 vs 26.5, P = 0.04 and FF: 168 vs 201 mg dL(-1) P = 0.01) and at 48 h n = 2 (MA: 29.7 vs 23.0, P = 0.02; R-time: 8.1 vs 6.7 mins, P = 0.05; alpha angle: 22.6 vs 26.5, P = 0.04; FF: 170 vs 208 mg dL(-1), P = 0.01). There were no significant differences in TPC, APTT or PT between patients that bled and those that did not at each time point. CONCLUSIONS: Thrombocytopenic HM patients experiencing bleeding are hypocoaguable on TEG((r)). PMID- 26132502 TI - Bariatric Surgery vs Lifestyle Intervention for Type 2 Diabetes Mellitus. PMID- 26132503 TI - What is the mechanism for in vivo loss of skeletal muscle function in elderly women? PMID- 26132504 TI - Subsequent growth performance and digestive physiology of broilers fed on starter diets containing spray-dried porcine plasma as a substitute for meat meal. AB - A 4 * 2 factorial experiment was conducted to investigate the effect of inclusion of spray-dried porcine plasma (SDPP), in lieu of meat meal, in the starter diet on performance and digestive physiology of broiler chickens between hatch and 35 d of age. Four levels of SDPP (0, 5, 10 or 20 g/kg) were included in the starter diets in lieu of meat meal on either wheat- or maize-based diets. Over the first 10 d, and throughout the 35-d experimental period, birds gained more body weight with increasing concentrations of SDPP regardless to the type of grain used. Inclusion of SDPP in the starter diet markedly improved feed per gain in the starter phase and across the 35-d study. There was no significant effect of the type of grain and its interaction with SDPP on the body weight gain and feed per gain for the two assessed periods. At d 10, the relative weight of the gizzard+proventriculus, spleen and liver increased with increasing concentrations of SDPP. At 24 d of age, the grain and SDPP inclusion significantly interacted, depressing the weight of bursa and spleen in birds that received the highest concentration of SDPP in the maize-based diet. Birds fed on the maize-based diets had higher relative weight of pancreas than those on the wheat-based diets. Increasing concentrations of SDPP in the starter diet improved the activities of maltase, sucrase and alkaline phosphatase at 24 d of age. The interaction of grain and SDPP concentration was significant for sucrase activity in birds on the wheat-based diets. Chickens on maize-based diets had higher alkaline phosphatase and maltase activities than those on wheat-based diets. Chicks that were offered SDPP-containing starter diets had longer villi, deeper crypts and lower villi/crypt than the control at 24 d of age regardless of the grain type used. Furthermore, longer villi and larger villi/crypt were found in chicken groups fed on wheat-based diets than those on maize-based diets. Chickens on maize-based diets had higher dressing percentage and relative breast weight than those on wheat-based diets at 35 d of age. It can be concluded that supplementation of starter diets with SDPP would be beneficial to the long-term growth of broiler chickens. The effect of the basal grain used in the diet is minimal. PMID- 26132505 TI - Rehabilitation in Madagascar: Challenges in implementing the World Health Organization Disability Action Plan. AB - OBJECTIVE: To provide an update on rehabilitation in Madagascar by using local knowledge to outline the potential barriers and facilitators for implementation of the World Health Organization (WHO) Disability Action Plan (DAP). METHODS: A 14-day extensive workshop programme (September-October 2014) was held at the University Hospital Antananarivo and Antsirabe, with the Department of Health Madagascar, by rehabilitation staff from Royal Melbourne Hospital, Australia. Attendees were rehabilitation professionals (n=29) from 3 main rehabilitation facilities in Madagascar, who identified various challenges faced in service provision, education and attitudes/approaches to people with disabilities. Their responses and suggested barriers/facilitators were recorded following consensus agreement, using objectives listed in the DAP. RESULTS: The barriers and facilitators outlined by participants in implementing the DAP objectives include: engagement of health professionals and institutions using a multi-sectoral approach, new partnerships, strategic collaboration, provision of technical assistance, future policy directions, and research and development. Other challenges for many basic policies included: access to rehabilitation services, geographical coverage, shortage of skilled work-force, limited info-technology systems; lack of care-models and facility/staff accreditation standards; limited health services infrastructure and "disconnect" between acute and community-based rehabilitation. CONCLUSION: The DAP summary actions were useful planning tools to improve access, strengthen rehabilitation services and community-based rehabilitation, and collate data for outcome research. PMID- 26132506 TI - Synthesis and Antifeedant Activity of Racemic and Optically Active Hydroxy Lactones with the p-Menthane System. AB - Two racemic and two enantiomeric pairs of new delta-hydroxy-gamma-lactones based on the p-menthane system were prepared from racemic and optically active cis- and trans-piperitols. The Johnson-Claisen rearrangement of the piperitols, epoxidation of the gammadelta-unsaturated esters, and acidic lactonization of the epoxy esters were described. The structures of the compounds were confirmed spectroscopically. The antifeedant activities of the hydroxy lactones and racemic piperitone were evaluated against three insect pests: lesser mealworm, Alphitobius diaperinus (Panzer); Colorado potato beetle, Leptinotarsa decemlineata (Say); and peach-potato aphid, Myzus persicae (Sulz.). The chemical transformation of piperitone by the introduction of a lactone moiety and a hydroxy group changed its antifeedant properties. Behavioral bioassays showed that the feeding deterrent activity depended on the insect species and the structure of the compounds. All hydroxy lactones deterred the settling of M. persicae. Among chewing insects, the highest sensitivity showed A. diaperinus adults. PMID- 26132507 TI - Psychometric Evidence of a Multidimensional Measure of Prosocial Behaviors for Spanish Adolescents. AB - Prior theories and scholars rarely distinguished between distinct forms of prosocial behaviors (i.e., actions intended to benefit others) and most scholars operationalize prosocial behaviors as a global construct. Furthermore, stringent tests of psychometric properties of prosocial behavior measures are rare, especially in countries other than the United States. The present study was designed to examine the structure and functions of a multidimensional measure of prosocial behaviors in youth from Spain. Six hundred and 66 adolescents (46% girls; M age = 15.33 years, SD = 0.47 years) from Valencia, Spain, completed the Prosocial Tendencies Measure-Revised (PTM-R), measures of sympathy, perspective taking, and a global measure of prosocial behavior. Results showed that the hypothesized 6-factor structure of the PTM-R had good fit, the best fit model as compared to alternative models, and that there were several unique patterns of relations between specific forms of prosocial behaviors and sympathy, perspective taking, and the global measure of prosocial behavior. Furthermore, although there were significant gender differences in some forms of prosocial behaviors, the structure of the PTM-R was equivalent across gender. Discussion focuses on the implications for theories and measurement of prosocial behaviors. PMID- 26132508 TI - In vivo topical application of acetyl aspartic acid increases fibrillin-1 and collagen IV deposition leading to a significant improvement of skin firmness. AB - OBJECTIVE: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. METHOD: Two separate double blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. RESULTS: Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin-firming active ingredient. CONCLUSION: In this study, we showed the in vivo efficacy of 1% A-A-A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti-ageing 'cosmeceutical' ingredient answering the needs of our key consumer base. PMID- 26132509 TI - Integrating transcriptomic and metabolomic analysis to understand natural leaf senescence in sunflower. AB - Leaf senescence is a complex process, which has dramatic consequences on crop yield. In sunflower, gap between potential and actual yields reveals the economic impact of senescence. Indeed, sunflower plants are incapable of maintaining their green leaf area over sustained periods. This study characterizes the leaf senescence process in sunflower through a systems biology approach integrating transcriptomic and metabolomic analyses: plants being grown under both glasshouse and field conditions. Our results revealed a correspondence between profile changes detected at the molecular, biochemical and physiological level throughout the progression of leaf senescence measured at different plant developmental stages. Early metabolic changes were detected prior to anthesis and before the onset of the first senescence symptoms, with more pronounced changes observed when physiological and molecular variables were assessed under field conditions. During leaf development, photosynthetic activity and cell growth processes decreased, whereas sucrose, fatty acid, nucleotide and amino acid metabolisms increased. Pathways related to nutrient recycling processes were also up regulated. Members of the NAC, AP2-EREBP, HB, bZIP and MYB transcription factor families showed high expression levels, and their expression level was highly correlated, suggesting their involvement in sunflower senescence. The results of this study thus contribute to the elucidation of the molecular mechanisms involved in the onset and progression of leaf senescence in sunflower leaves as well as to the identification of candidate genes involved in this process. PMID- 26132510 TI - Updates in the approach to intrathoracic sarcomas. AB - Primary intrathoracic sarcomas constitute a rare, heterogeneous group of neoplasms that occur in the lung parenchyma, pleura, and mediastinum. Although pathologically diverse, they frequently show similar clinical and radiological features, and accurate histopathological diagnosis is therefore crucial for correct management and prognostication. The characterization of sarcomas can be difficult, as there is frequent overlap between the histological patterns of benign and malignant lesions, and between different malignant tumours and with non-mesenchymal neoplasms. This is particularly critical within the thorax, where many spindle cell neoplasms represent tumours of epithelial origin or metastatic disease. Immunohistochemistry and molecular genetic techniques are important ancillary contributors to histological interpretation, but several groups of tumours still lack reliable immunohistochemical markers or reproducible genetic changes. We review the pathology of the major types of intrathoracic sarcoma with reference to clinical factors, morphology, immunohistochemistry, and molecular genetics. PMID- 26132511 TI - Intraoperative biomarkers in renal transplantation. AB - The emerging need for biomarkers in the management of renal transplantation is highlighted by the severity of related complications such as acute renal failure and ischaemia/reperfusion injury (IRI) and by the increasing efforts to identify novel markers of these events to predict and monitor delayed graft function (DGF) and long-term outcome. In clinical studies candidate markers such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and interleukin-18 have been demonstrated to be valid biomarkers with high predictive value for DFG in a post-transplant setting. However, studies investigating biomarkers for early diagnosis of IRI and assumable DGF as well as identification of potential graft recipients at increased risk at the time point of transplantation lack further confirmation and translation into clinical practice. This review summarizes the current literature on the value of IRI biomarkers in outcome prediction following renal transplantation as well their capacity as surrogate end points from an intraoperative perspective. PMID- 26132512 TI - Evaluation of the use of low-level laser therapy in pain control in orthodontic patients: A randomized split-mouth clinical trial. AB - OBJECTIVE: To evaluate the effect of using low-level laser therapy (LLLT) to control pain and discomfort during orthodontic treatment. MATERIALS AND METHODS: A randomized, split-mouth clinical trial was conducted with 30 volunteers in need of orthodontic treatment, of both genders, aged between 18 and 40 years, who were randomly divided into two groups. One hemiarch was considered the exposed group (EG) and the other, the placebo group (PG). Both groups had elastic separators placed mesially and distally to the first molars of the two hemiarches at different times. The EG received an AIGaAs diode LLLT (810 nm, 100 mW, 2J/cm(2)) application for 15 seconds per point (interdental papilla at the mesial, distal, and near the root apex) immediately after separator placement on the maxillary right side. The PG also had elastics placed around the maxillary right molars, but received only simulated LLLT application. The elastics were left in place for 5 days, and after a waiting period of 1 week, they were inserted on the left side in both groups; however, the order of laser application was changed. While the separator remained in place, the patient marked his degree of perceived discomfort on a Visual Analog Scale (VAS) at 5 minutes (T0), 24 hours (T1), and 120 hours (T2), after LLLT application. RESULTS: A statistically significant difference was observed (P < .005) in reducing discomfort in the exposed group compared with the placebo group. This reduction of discomfort in the EG was observed at all time intervals. CONCLUSIONS: A sincle AIGaAs diode LLLT application may be indicated for the control or reduction of pain in the early stages of orthodontic treatment. PMID- 26132513 TI - Abnormal behavior of threshold voltage shift in bias-stressed a-Si:H thin film transistor under extremely high intensity illumination. AB - We report on the unusual behavior of threshold voltage turnaround in a hydrogenated amorphous silicon (a-Si:H) thin film transistor (TFT) when biased under extremely high intensity illumination. The threshold voltage shift changes from negative to positive gate bias direction after ~30 min of bias stress even when the negative gate bias stress is applied under high intensity illumination (>400 000 Cd/cm(2)), which has not been observed in low intensity (~6000 Cd/cm(2)). This behavior is more pronounced in a low work function gate metal structure (Al: 4.1-4.3 eV), compared to the high work function of Cu (4.5-5.1 eV). Also this is mainly observed in shorter wavelength of high photon energy illumination. However, this behavior is effectively prohibited by embedding the high energy band gap (~8.6 eV) of SiOx in the gate insulator layer. These imply that this behavior could be originated from the injection of electrons from gate electrode, transported and trapped in the electron trap sites of the SiNx/a-Si:H interface, which causes the shift of threshold voltage toward positive gate bias direction. The results reported here can be applicable to the large-sized outdoor displays which are usually exposed to the extremely high intensity illumination. PMID- 26132514 TI - The role of amorphous precursors in the crystallization of La and Nd carbonates. AB - Crystalline La and Nd carbonates can be formed from poorly-ordered nanoparticulate precursors, termed amorphous lanthanum carbonate (ALC) and amorphous neodymium carbonate (ANC). When reacted in air or in aqueous solutions these precursors show highly variable lifetimes and crystallization pathways. We have characterized these precursors and the crystallization pathways and products with solid-state, spectroscopic and microscopic techniques to explain the differences in crystallization mechanisms between the La and Nd systems. ALC and ANC consist of highly hydrated, 10-20 nm spherical nanoparticles with a general formula of REE2(CO3)3.5H2O (REE = La, Nd). The stabilities differ by ~2 orders of magnitude, with ANC being far more stable than ALC. This difference is due to the Nd(3+) ion having a far higher hydration energy compared to the La(3+) ion. This, together with temperature and reaction times, leads to clear differences not only in the kinetics and mechanisms of crystallization of the amorphous precursor La- and Nd-carbonate phases but also in the resulting crystallite sizes and morphologies of the end products. All crystalline La and Nd carbonates developed spherulitic morphologies when crystallization occurred from hydrous phases in solution at temperatures above 60 degrees C (La system) and 95 degrees C (Nd system). We suggest that spherulitic growth occurs due to a rapid breakdown of the amorphous precursors and a concurrent rapid increase in supersaturation levels in the aqueous solution. The kinetic data show that the crystallization pathway for both La and Nd carbonate systems is dependent on the reaction temperature and the ionic potential of the REE(3+) ion. PMID- 26132515 TI - Societal Norms Rather Than Sexual Orientation Influence Kin Altruism and Avuncularity in Tribal Urak-Lawoi, Italian, and Spanish Adult Males. AB - Homosexual males could balance their low fitness by increasing benefits to relatives either through kin-directed altruism or by avuncularity (altruistic behavior toward the children of siblings). Evidence in support of kin selection and avuncularity includes the fact that homosexuals seem to be more empathic and altruistic than heterosexuals. Other studies have not confirmed behaviors that increase kin altruism in homosexuals. We explored altruistic behavior and avuncularity in a sample of 278 subjects, either homosexual or heterosexual, from three populations: Italian, Spanish, and Urak-Lawoi, a Southeast Asian tribal population. Among the Urak-Lawoi, the kathoeys, androphilic men who dress and behave as women, were compared with heterosexuals. All populations were rated for societal norms on the expression of affiliative behavior. No greater kin altruism or avuncularity among the kathoeys or in homosexuals in either Mediterranean population was found. Greater avuncularity and kin-directed altruism, independent of sexual orientation, were found among the Urak-Lawoi, and these traits were the least prevalent among the Italians, corresponding to different societal norms. The increase in kin altruism and avuncularity was associated in all males with societal differences and norms on general altruism toward nonkin children, suggesting it is not an adaptive design to maintain homosexuality in humans. PMID- 26132518 TI - Synthetic Cannabinoids. AB - Synthetic cannabinoids (SCBs), also known under the brand names of "Spice," "K2," "herbal incense," "Cloud 9," "Mojo" and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential. There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors. Although both Delta tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than is natural cannabis. This is likely due to SCBs being direct agonists of the cannabinoid receptors, whereas THC is a partial agonist. Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants. The largest group of users is men in their 20s who participate in polydrug use. The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain. Acute kidney injury has also been strongly associated with SCB use. Treatment mostly involves symptom management and supportive care. More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes. PMID- 26132516 TI - Formative Evaluation of a Text Messaging Intervention to Promote Varenicline Adherence Among Tobacco-Dependent Persons with HIV. AB - Few published studies describe processes in the development of mobile health interventions. This study reports data from a formative evaluation of a text messaging intervention being developed to increase adherence to smoking cessation medication (varenicline) among tobacco-dependent persons with HIV/AIDS. Four focus groups were conducted (N = 29) using a mixed-methods approach to assess: (a) beliefs and preferences regarding the use of varenicline, (b) preferences for receiving tobacco-related texts, and (c) the acceptability of draft text messages. Themes that emerged from the focus groups were that (a) participants were cautious and wanted to discuss varenicline carefully with health care providers, (b) participants preferred simple messages that were positive and encouraging, (c) messages should emphasize tobacco cessation and not varenicline adherence, and (d) texts would serve as a reminder about goals and foster support and connectedness with the health care team. Overall, 47 out of the 100 messages received a grade of C or less (rated on a 5-point grade scale: A, B, C, D, or F), the majority of which focused on medication adherence. All participants reported that they were likely to read the messages. The majority (64%) indicated that they preferred receiving 2 or more messages per day. Gathering systematic participant feedback provides critical input in intervention planning. PMID- 26132519 TI - Bronchobiliary Fistula Presenting With Recurrent Pneumonia and Cholelithoptysis. PMID- 26132520 TI - Horses for courses: reaching outside drug-like chemical space for inhibitors of challenging drug targets. PMID- 26132521 TI - Gold nanoparticles to improve HIV drug delivery. AB - BACKGROUND: Antiretroviral therapy (ART) has improved lifespan and quality of life of patients infected with the HIV-1. However, ART has several potential limitations, including the development of drug resistance and suboptimal penetration to selected anatomic compartments. Improving the delivery of antiretroviral molecules could overcome several of the limitations of current ART. RESULTS & CONCLUSION: Two to ten nanometer diameter inorganic gold crystals serve as a base scaffold to combine molecules with an array of properties in its surface. We show entry into different cell types, antiviral activity of an HIV integrase inhibitor conjugated in a gold nanoparticle and penetration into the brain in vivo without toxicity. Herein, gold nanoparticles prove to be a promising tool to use in HIV therapy. PMID- 26132522 TI - Steroidal scaffolds as FXR and GPBAR1 ligands: from chemistry to therapeutical application. AB - Bile acids (BAs) are experiencing a new life. Next to their ancestral roles in lipid digestion and solubilization, BAs are today recognized signaling molecules involved in many physiological functions. These signaling pathways involve the activation of metabolic nuclear receptors, mainly the BA sensor FXR, and the dedicated membrane G protein-coupled receptor, GPBAR1 (TGR5). As a consequence, the discovery of GPBAR1/FXR selective or dual modulators represents an important answer to the urgent demand of new pharmacological opportunity for several human diseases including dyslipidemia, cholestasis, nonalcoholic steatohepatitis, Type 2 diabetes and inflammation. Targeted oriented discovery of natural compounds and medicinal chemistry manipulation have allowed the development of promising drug candidates. PMID- 26132523 TI - The PI3K/Akt/PTEN/mTOR pathway: a fruitful target for inducing cell death in rheumatoid arthritis? AB - PI3K/Akt/mTOR signaling regulates diverse cellular processes. Abnormal PI3K/Akt/mTOR signaling is a characteristic feature of cancer. As such inhibition of PI3K/Akt/mTOR signaling using small molecule inhibitors has been a focus of recently developed anticancer drugs. Rheumatoid arthritis and psoriatic arthritis are autoimmune-mediated inflammatory diseases. PI3K signaling could now be targeted to determine its contribution to rheumatoid and psoriatic arthritis where deregulated proliferation and aberrant survival of activated immune cells, macrophages, monocytes, dendritic cells and synovial fibroblasts significantly overlap with abnormal growth of cancer cells. The results of some recent studies in psoriatic arthritis using PI3K signaling inhibitors suggests that small molecule inhibitor strategies directed at PI3K signaling may be a useful future therapy for immune-mediated arthritis. PMID- 26132524 TI - Progress in the research of GPIIb/IIIa antagonists. AB - This review covers the recent advances in the development of small RGD (Arg-Gly Asp sequence) containing peptides and their mimetics as potential antithrombotic agents. Glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists include monoclonal antibodies, RGD peptides, peptide hybrids and nonpeptide mimetics. The current trend in the development of nonpeptide mimetics is clearly directed toward orally active and safe antithrombotic drug candidates. But several nonpeptide mimetics, being evaluated for their oral activity in human clinical trials, are currently not approved for clinical use due to poor safety profile. It is expected that newer and more effective nonpeptide mimetics will be developed in the near future. PMID- 26132525 TI - Isatin sulfonamides: potent caspases-3 and -7 inhibitors, and promising PET and SPECT radiotracers for apoptosis imaging. AB - Caspases-3 and -7 play an essential role in apoptosis. Isatin sulfonamides have been identified as potent inhibitors of these executing caspases. Besides pharmacological application, these compounds can also serve as recognition units to target caspases using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) when labeled with a positron or a gamma emitter. Fluorinated, alkylated, arylated isatin derivatives, in addition to derivatives modified with heterocycles, have been prepared in order to improve their binding potency, selectivity and metabolic stability. Structural optimization has led to stable, highly active inhibitors, which after labeling have been applied in PET studies in tumor mouse models and for first preclinical and clinical investigations with healthy human volunteers. The results support further development of such radiotracers for clinical apoptosis imaging. PMID- 26132526 TI - Activity and property landscape modeling is at the interface of chemoinformatics and medicinal chemistry. AB - Property landscape modeling (PLM) methods are at the interface of experimental sciences and computational chemistry. PLM are becoming a common strategy to describe systematically structure-property relationships of datasets. Thus far, PLM have been used mainly in medicinal chemistry and drug discovery. Herein, we survey advances on key topics on PLM with emphasis on questions often raised regarding the outcomes of the property landscape studies. We also emphasize on concepts of PLM that are being extended to other experimental areas beyond drug discovery. Topics discussed in this paper include applications of PLM to further characterize protein-ligand interactions, the utility of PLM as a quantitative and descriptive approach, and the statistical validation of property cliffs. PMID- 26132527 TI - Engineering 3D Cellularized Collagen Gels for Vascular Tissue Regeneration. AB - Synthetic materials are known to initiate clinical complications such as inflammation, stenosis, and infections when implanted as vascular substitutes. Collagen has been extensively used for a wide range of biomedical applications and is considered a valid alternative to synthetic materials due to its inherent biocompatibility (i.e., low antigenicity, inflammation, and cytotoxic responses). However, the limited mechanical properties and the related low hand-ability of collagen gels have hampered their use as scaffold materials for vascular tissue engineering. Therefore, the rationale behind this work was first to engineer cellularized collagen gels into a tubular-shaped geometry and second to enhance smooth muscle cells driven reorganization of collagen matrix to obtain tissues stiff enough to be handled. The strategy described here is based on the direct assembling of collagen and smooth muscle cells (construct) in a 3D cylindrical geometry with the use of a molding technique. This process requires a maturation period, during which the constructs are cultured in a bioreactor under static conditions (without applied external dynamic mechanical constraints) for 1 or 2 weeks. The "static bioreactor" provides a monitored and controlled sterile environment (pH, temperature, gas exchange, nutrient supply and waste removal) to the constructs. During culture period, thickness measurements were performed to evaluate the cells-driven remodeling of the collagen matrix, and glucose consumption and lactate production rates were measured to monitor the cells metabolic activity. Finally, mechanical and viscoelastic properties were assessed for the resulting tubular constructs. To this end, specific protocols and a focused know-how (manipulation, gripping, working in hydrated environment, and so on) were developed to characterize the engineered tissues. PMID- 26132528 TI - Antiviral Matrine-Type Alkaloids from the Rhizomes of Sophora tonkinensis. AB - Three new matrine-type alkaloids, (+)-5alpha-hydroxyoxysophocarpine (1), (-) 12beta-hydroxyoxysophocarpine (2), and (+)-5alpha-hydroxylemannine (3), along with 14 known analogues, (-)-sophocarpine (4), (-)-5alpha-hydroxysophocarpine (5), (-)-9alpha-hydroxysophocarpine (6), (+)-12alpha-hydroxysophocarpine (7), (-) 12beta-hydroxysophocarpine (8), (+)-oxysophocarpine (9), (+)-matrine (10), (+) sophoranol (11), (+)-9alpha-hydroxymatrine (12), (-)-14beta-hydroxymatrine (13), (+)-oxymatrine (14), (+)-5alpha-hydroxyoxymatrine (15), (-)-14beta hydroxyoxymatrine (16), and (+)-sophoramine (17), were isolated from the rhizomes of Sophora tonkinensis. Their structures were elucidated via spectrometric data analyses, and the absolute configurations were established by single-crystal X ray diffraction and ECD data. Alkaloids 2, 6, 11, and 13 exhibited antiviral activity against the Coxsackie virus B3 (CVB3), with IC50 values of 26.62-252.18 MUM, and alkaloids 7, 8, and 17 inhibited influenza virus A/Hanfang/359/95 (H3N2) replication with IC50 values of 63.07-242.46 MUM. PMID- 26132529 TI - Induced Pluripotent Stem Cell-Derived Conditioned Medium Attenuates Acute Kidney Injury by Downregulating the Oxidative Stress-Related Pathway in Ischemia Reperfusion Rats. AB - Teratoma-like formation addresses a critical safety concern for the potential utility of induced pluripotent stem cells (iPSCs). Therefore, therapy utilizing iPSC-derived conditioned medium (iPSC-CM) for acute kidney injury (AKI) has attracted substantial interest. A recent study showed that iPSC-CM effectively alleviated ventilator-induced lung injury in rats. It prompts us to assess the therapeutic effects of iPSC-CM on ischemic AKI. First, we assessed the changes in renal function and tubular cell apoptosis by intraperitoneal administration of iPSC-CM to ischemia-reperfusion (I/R) rats. Second, we explored the oxidative stress-related pathway in the apoptosis of renal tubular cells subjected to hypoxia-reoxygenation (H/R). Administration of iPSC-CM significantly improved renal function and protected tubular cells against apoptosis in rats with I/R AKI, and the optimal effect was observed at the 50-fold concentrated iPSC-CM. iPSC-CM also mitigated the H/R-induced apoptosis of NRK-52E cells in vitro. Reactive oxygen species (ROS) production was augmented in kidneys following I/R and in NRK-52E cells subjected to H/R. Meanwhile, expressions of phosphorylated p38 MAPK, TNF-alpha, and cleaved caspase 3 and NF-kappaB activity were consistently increased in vivo and in vitro. Following administration of iPSC-CM, ROS production was abolished, and inflammatory cytokine expression was significantly suppressed. Annexin V-propidium iodide flow cytometry and in situ TUNEL assay further showed that iPSC-CM markedly attenuated H/R- or I/R-induced tubular cell apoptosis. Intriguingly, treatment with iPSC-CM significantly improved the survival of rats with I/R-induced AKI. iPSC-CM represents a favorable source of stem cell-based therapy and may serve as a potential therapeutic strategy for kidney repair in ischemic AKI. PMID- 26132530 TI - Primary and secondary ataxias. AB - PURPOSE OF REVIEW: This article discusses recent advances in the understanding of clinical and genetic aspects of primary ataxias, including congenital, autosomal recessive, autosomal dominant, episodic, X-linked, and mitochondrial ataxias, as well as idiopathic degenerative and secondary ataxias. RECENT FINDINGS: Many important observations have been published in recent years in connection with primary ataxias, particularly new loci and genes. The most commonly inherited ataxias may present with typical and atypical phenotypes. In the group of idiopathic degenerative ataxias, genes have been found in patients with multiple system atrophy type C. Secondary ataxias represent an important group of sporadic, cerebellar, and afferent/sensory ataxias. SUMMARY: Knowledge of primary ataxias has been growing rapidly in recent years. Here we review different forms of primary ataxia, including inherited forms, which are subdivided into congenital, autosomal recessive cerebellar ataxias, autosomal dominant cerebellar ataxias, episodic ataxias, X-linked ataxias, and mitochondrial ataxias, as well as sporadic ataxias and idiopathic degenerative ataxias. Secondary or acquired ataxias are also reviewed and the most common causes are discussed. PMID- 26132531 TI - In-vivo brain neuroimaging provides a gateway for integrating biological and clinical biomarkers of Alzheimer's disease. AB - PURPOSE OF REVIEW: Only 5% of the Alzheimer's cases are explained by genetic mutations, whereas the remaining 95% are sporadic. The pathophysiological mechanisms underlying sporadic Alzheimer's disease are not well understood, suggesting a complex multifactorial cause. This review summarizes the recent findings on research aiming to show how biomarkers can be used for revealing the underlying mechanisms of preclinical stage Alzheimer's disease and help in their diagnosis. RECENT FINDINGS: The undisputed successful publicly accessible repositories provide longitudinal brain images, clinical, genetic and proteomic information of Alzheimer's disease. By combining with increasingly sophisticated data analysis methods, it is a great opportunity for searching new biomarkers. Innovative studies validated theoretical models of disease progression demonstrating the sequential ordering of well-established biomarkers. Novel observations shed light on the interaction between biomarkers to confirm that disease progression is related to multiple pathological factors. A typical example is the tau-associated neuronal toxicity that can be additionally potentiated by amyloid beta peptides. To increase further the complexity, studies report specific impact of common genetic variants that can be traced from childhood through middle age up to the symptomatic onset of Alzheimer's disease. SUMMARY: The discovery of efficient therapies to prevent the disease or modify the progression of disease requires a more thorough understanding of the underlying biological processes. Neuroimaging, genetic and proteomic biomarkers for Alzheimer's disease are critically discussed and proposed to be included in clinical descriptions and diagnostic guidelines. PMID- 26132532 TI - Advances in MRI-based computational neuroanatomy: from morphometry to in-vivo histology. AB - PURPOSE OF REVIEW: Current computational neuroanatomy based on MRI focuses on morphological measures of the brain. We present recent methodological developments in quantitative MRI (qMRI) that provide standardized measures of the brain, which go beyond morphology. We show how biophysical modelling of qMRI data can provide quantitative histological measures of brain tissue, leading to the emerging field of in-vivo histology using MRI (hMRI). RECENT FINDINGS: qMRI has greatly improved the sensitivity and specificity of computational neuroanatomy studies. qMRI metrics can also be used as direct indicators of the mechanisms driving observed morphological findings. For hMRI, biophysical models of the MRI signal are being developed to directly access histological information such as cortical myelination, axonal diameters or axonal g-ratio in white matter. Emerging results indicate promising prospects for the combined study of brain microstructure and function. SUMMARY: Non-invasive brain tissue characterization using qMRI or hMRI has significant implications for both research and clinics. Both approaches improve comparability across sites and time points, facilitating multicentre/longitudinal studies and standardized diagnostics. hMRI is expected to shed new light on the relationship between brain microstructure, function and behaviour, both in health and disease, and become an indispensable addition to computational neuroanatomy. PMID- 26132533 TI - Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation. AB - Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically. PMID- 26132534 TI - Following Coupled Electronic-Nuclear Motion through Conical Intersections in the Ultrafast Relaxation of beta-Apo-8'-carotenal. AB - Ultrafast transient electronic absorption, one- and two- dimensional electronic vibrational spectroscopies were used to study the nonradiative relaxation dynamics of beta-apo-8'-carotenal (bapo), a model aldehyde containing carotenoid, in cyclohexane and acetonitrile solutions. 2D electronic-vibrational (2DEV) spectroscopy allows for a direct correlation between the intrinsically coupled electronic and vibrational degrees of freedom, which are thought to play an important role in driving relaxation of bapo from the bright S2 and lower-lying dark S1 state. Line shapes of features in the 2DEV spectra allow us to make more definitive assignments of excited state vibrations of bapo in acetonitrile. Anisotropy studies definitively demonstrate that the excited state dynamics of bapo do not involve a trans-cis isomerization, counter to prior hypotheses. For specific vibrational modes, the electronic and vibrational line shapes remain correlated beyond the decay of the S2 excited state, indicating that the transfer of molecules to the S1 state is impulsive and involves a conical intersection in the vertical Franck-Condon region. PMID- 26132535 TI - Family composition and symptom severity among Veterans with comorbid PTSD and substance use disorders. AB - Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) frequently co-occur and affect a substantial proportion of military Veterans. Although the impact of parental PTSD and SUD on child development is well-documented, little is known about the influence of family composition on PTSD/SUD symptom severity. The present study investigated children in the home as an independent risk factor for symptom severity in a sample of treatment-seeking Veterans (N = 94; 92% male) with comorbid PTSD/SUD. Twenty-seven percent of the sample had minor children (age 18 or younger) living in the home. Veterans with children in the home evidenced significantly higher PTSD symptomatology as measured by the Clinical Administered PTSD Scale (CAPS; M = 82.65 vs. M = 72.17; t = -2.18; p < .05), and reported using marijuana more frequently than Veterans without children in the home (34% vs. 13% of past 60 days; t = -2.35, p < .05). In a multivariate model, having children in the home accounted for unique variance (DeltaR(2) = .07) in PTSD severity after accounting for a range of covariates; however, having children in the home did not account for unique variance in substance use. Directions for future research as well as potential clinical implications for parents seeking treatment for PTSD/SUD are discussed. PMID- 26132536 TI - Electronic cigarette use and its association with smoking in Hong Kong Chinese adolescents. AB - BACKGROUND: Electronic cigarettes (e-cigarettes) are increasingly used in adolescents with unknown impacts on conventional cigarette smoking. We examined the associations of e-cigarette use with smoking intention, nicotine addiction and smoking cessation in Chinese adolescents. METHODS: A total of 45,128 students (age 14.6 +/- 1.9; boys 51.4%) from 75 randomly selected schools in Hong Kong reported e-cigarette use (in the past 30 days), conventional cigarette use and socio-demographic characteristics in an anonymous questionnaire survey. Adjusted odds ratios (AORs) of intention to smoke, morning smoking urge, intention to quit and quit attempts; and beta-coefficient (beta) of cigarette consumption per day were calculated in relation to e-cigarette use. RESULTS: E-cigarette use was associated with intention to smoke with an AOR (95% CI) of 1.74 (1.30-2.31) in all students, 2.18 (1.12-4.23) in never and 2.79 (2.05-3.79) in ever smokers (non significant interaction by smoking status). The associations were also significant in experimental and former smokers but not in current smokers. In current smokers, e-cigarette use was significantly associated with heavier smoking (beta 2.54, 95% CI 1.28-3.81) and morning smoking urge (AOR 2.54, 95% CI 1.50-3.11), and non-significantly associated with lower quit intention (0.76, 0.52-1.09) and attempts (0.80, 0.56-1.23). CONCLUSIONS: E-cigarette use was associated with smoking intention in never, experimental and former smokers in Hong Kong Chinese adolescents. In current smokers, e-cigarette use was associated with nicotine addiction but not quit intention and attempts. Prospective studies with detailed measurements on e-cigarette use are warranted for further studies. PMID- 26132537 TI - Response to "Comment on 'Fluorotechnology Is Critical to Modern Life: The FluoroCouncil Counterpoint to the Madrid Statement'". PMID- 26132538 TI - Molecular dynamics investigations of BioH protein substrate specificity for biotin synthesis. AB - BioH, an enzyme of biotin synthesis, plays an important role in fatty acid synthesis which assembles the pimelate moiety. Pimeloyl-acyl carrier protein (ACP) methyl ester, which is long known to be a biotin precursor, is the physiological substrate of BioH. Azelayl methyl ester, which has a longer chain than pimeloyl methyl ester, conjugated to ACP is also indeed accepted by BioH with very low rate of hydrolysis. To date, the substrate specificity for BioH and the molecular origin for the experimentally observed rate changes of hydrolysis by the chain elongation have remained elusive. To this end, we have investigated chain elongation effects on the structures by using the fully atomistic molecular dynamics simulations combined with binding free energy calculations. The results indicate that the substrate specificity is determined by BioH together with ACP. The added two methylenes would increase the structural flexibility by protein motions at the interface of ACP and BioH, instead of making steric clashes with the side chains of the BioH hydrophobic cavity. On the other hand, the slower hydrolysis of azelayl substrate is suggested to be associated with the loose of contacts between BioH and ACP, and with the lost electrostatic interactions of two ionic/hydrogen bonding networks at the interface of the two proteins. The present study provides important insights into the structure-function relationships of the complex of BioH with pimeloyl-ACP methyl ester, which could contribute to further understanding about the mechanism of the biotin synthetic pathway, including the catalytic role of BioH. PMID- 26132548 TI - Noninvasive Positive-Pressure Ventilation in Acute Respiratory Distress Syndrome in Patients With Acute Pancreatitis: A Retrospective Cohort Study. AB - OBJECTIVES: Noninvasive positive-pressure ventilation (NPPV) in acute respiratory distress syndrome (ARDS) is controversial. We aimed to assess the efficacy of NPPV on ARDS in acute pancreatitis (AP). METHODS: In this retrospective, single center cohort study, demographic data, clinical and biochemical parameters of AP and developed ARDS on admission as well as before and after use of NPPV, and clinical outcomes were retrieved from the medical record database. Degrees of ARDS at presentation were retrospectively classified using the Berlin Definition. RESULTS: Of 379 patients identified, 127 were eligible for inclusion and had NPPV for more than 24 hours. There were 44 mild, 64 moderate, and 19 severe patients with ARDS at presentation; endotracheal intubation rates were 0% (0/44), 23.4% (15/64), and 47.4% (9/19); and the mortality rates were 0% (0/44), 9.4% (6/64), and 15.8% (3/19), respectively. After NPPV treatment, systolic pressure, heart rate, respiratory rate, and fraction of inspired oxygen decreased, whereas oxygen saturation increased significantly in the NPPV success group compared with the failed group. Similar findings were also observed between survivors and nonsurvivors. CONCLUSIONS: Noninvasive positive-pressure ventilation may be an effective option for the initial treatment of ARDS patients in AP, but the use of NPPV should be applied prudently in the most severe cases. PMID- 26132549 TI - Two-photon Imaging of Intracellular Ca2+ Handling and Nitric Oxide Production in Endothelial and Smooth Muscle Cells of an Isolated Rat Aorta. AB - Calcium is a very important regulator of many physiological processes in vascular tissues. Most endothelial and smooth muscle functions highly depend on changes in intracellular calcium ([Ca(2+)]i) and nitric oxide (NO). In order to understand how [Ca(2+)]i, NO and downstream molecules are handled by a blood vessel in response to vasoconstrictors and vasodilators, we developed a novel technique that applies calcium-labeling (or NO-labeling) dyes with two photon microscopy to measure calcium handling (or NO production) in isolated blood vessels. Described here is a detailed step-by-step procedure that demonstrates how to isolate an aorta from a rat, label calcium or NO within the endothelial or smooth muscle cells, and image calcium transients (or NO production) using a two photon microscope following physiological or pharmacological stimuli. The benefits of using the method are multi-fold: 1) it is possible to simultaneously measure calcium transients in both endothelial cells and smooth muscle cells in response to different stimuli; 2) it allows one to image endothelial cells and smooth muscle cells in their native setting; 3) this method is very sensitive to intracellular calcium or NO changes and generates high resolution images for precise measurements; and 4) described approach can be applied to the measurement of other molecules, such as reactive oxygen species. In summary, application of two photon laser emission microscopy to monitor calcium transients and NO production in the endothelial and smooth muscle cells of an isolated blood vessel has provided high quality quantitative data and promoted our understanding of the mechanisms regulating vascular function. PMID- 26132550 TI - Neutral "Cp-Free" Silyl-Lanthanide(II) Complexes: Synthesis, Structure, and Bonding Analysis. AB - Complexes featuring lanthanide silicon bonds represent a research area still in its infancy. Herein, we report a series of Cp-free lanthanide (+II) complexes bearing sigma-bonded silyl ligands. By reactions of LnI2 (Ln = Yb, Eu, Sm) either with a 1,4-oligosilanyl dianion [K-Si(SiMe3)2SiMe2SiMe2Si(SiMe3)2-K)] (1) or with 2 (Me3Si)3SiK (3) the corresponding neutral metallacyclopentasilanes ({Me2Si(Me3Si)2Si}2)Ln.(THF)4 (Ln = Yb (2a), Eu (2b), Sm (2c)), or the disilylated complexes ({Me3Si}3Si)2Ln.(THF)3 (Ln = Yb (4a), Eu (4b), Sm (4c)), were selectively obtained. Complexes 2b, 2c, 4b, and 4c represent the first examples of structurally characterized Cp-free Eu and Sm complexes with silyl ligands. In both series, a linear correlation was observed between the Ln-Si bond lengths and the covalent radii of the corresponding lanthanide metals. Density functional theory calculations were also carried out for complexes 2a-c and 4a-c to elucidate the bonding situation between the Ln(+II) centers and Si. PMID- 26132551 TI - Complete 1 H NMR assignment of cedranolides. AB - Complete and unambiguous 1 H NMR chemical shift assignment of alpha-cedrene (2) and cedrol (9), as well as for alpha-pipitzol (1), isocedrol (10), and the six related compounds 3-8 has been established by iterative full spin analysis using the PERCH NMR software (PERCH Solutions Ltd., Kuopio, Finland). The total sets of coupling constants are described and correlated with the conformational equilibria of the five-membered ring of 1-10, which were calculated using the complete basis set method. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26132552 TI - Confocal Raman Microscopy for pH-Gradient Preconcentration and Quantitative Analyte Detection in Optically Trapped Phospholipid Vesicles. AB - The ability of a vesicle membrane to preserve a pH gradient, while allowing for diffusion of neutral molecules across the phospholipid bilayer, can provide the isolation and preconcentration of ionizable compounds within the vesicle interior. In this work, confocal Raman microscopy is used to observe (in situ) the pH-gradient preconcentration of compounds into individual optically trapped vesicles that provide sub-femtoliter collectors for small-volume samples. The concentration of analyte accumulated in the vesicle interior is determined relative to a perchlorate-ion internal standard, preloaded into the vesicle along with a high-concentration buffer. As a guide to the experiments, a model for the transfer of analyte into the vesicle based on acid-base equilibria is developed to predict the concentration enrichment as a function of source-phase pH and analyte concentration. To test the concept, the accumulation of benzyldimethylamine (BDMA) was measured within individual 1 MUm phospholipid vesicles having a stable initial pH that is 7 units lower than the source phase. For low analyte concentrations in the source phase (100 nM), a concentration enrichment into the vesicle interior of (5.2 +/- 0.4) * 10(5) was observed, in agreement with the model predictions. Detection of BDMA from a 25 nM source-phase sample was demonstrated, a noteworthy result for an unenhanced Raman scattering measurement. The developed model accurately predicts the falloff of enrichment (and measurement sensitivity) at higher analyte concentrations, where the transfer of greater amounts of BDMA into the vesicle titrates the internal buffer and decreases the pH gradient. The predictable calibration response over 4 orders of magnitude in source-phase concentration makes it suitable for quantitative analysis of ionizable compounds from small-volume samples. The kinetics of analyte accumulation are relatively fast (~15 min) and are consistent with the rate of transfer of a polar aromatic molecule across a gel-phase phospholipid membrane. PMID- 26132553 TI - Effect of Internet-Based Cognitive Apprenticeship Model (i-CAM) on Statistics Learning among Postgraduate Students. AB - Because students' ability to use statistics, which is mathematical in nature, is one of the concerns of educators, embedding within an e-learning system the pedagogical characteristics of learning is 'value added' because it facilitates the conventional method of learning mathematics. Many researchers emphasize the effectiveness of cognitive apprenticeship in learning and problem solving in the workplace. In a cognitive apprenticeship learning model, skills are learned within a community of practitioners through observation of modelling and then practice plus coaching. This study utilized an internet-based Cognitive Apprenticeship Model (i-CAM) in three phases and evaluated its effectiveness for improving statistics problem-solving performance among postgraduate students. The results showed that, when compared to the conventional mathematics learning model, the i-CAM could significantly promote students' problem-solving performance at the end of each phase. In addition, the combination of the differences in students' test scores were considered to be statistically significant after controlling for the pre-test scores. The findings conveyed in this paper confirmed the considerable value of i-CAM in the improvement of statistics learning for non-specialized postgraduate students. PMID- 26132556 TI - Copper-Catalyzed gamma-Sulfonylation of alpha,beta-Unsaturated Carbonyl Compounds by Means of Silyl Dienol Ethers. AB - A regioselective method for the introduction of sulfonyl groups at the gamma carbon of enone systems is reported. Using a copper catalyst and readily available sulfonyl chlorides, a range of silyl dienol ethers are sulfonylated in good yield under mild reaction conditions. The sulfone derivatives formed are poised for further synthetic manipulations as demonstrated by regioselective alkylations. PMID- 26132554 TI - Functional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality. AB - Viruses often encode proteins with multiple functions due to their compact genomes. Existing approaches to identify functional residues largely rely on sequence conservation analysis. Inferring functional residues from sequence conservation can produce false positives, in which the conserved residues are functionally silent, or false negatives, where functional residues are not identified since they are species-specific and therefore non-conserved. Furthermore, the tedious process of constructing and analyzing individual mutations limits the number of residues that can be examined in a single study. Here, we developed a systematic approach to identify the functional residues of a viral protein by coupling experimental fitness profiling with protein stability prediction using the influenza virus polymerase PA subunit as the target protein. We identified a significant number of functional residues that were influenza type-specific and were evolutionarily non-conserved among different influenza types. Our results indicate that type-specific functional residues are prevalent and may not otherwise be identified by sequence conservation analysis alone. More importantly, this technique can be adapted to any viral (and potentially non viral) protein where structural information is available. PMID- 26132555 TI - Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes. AB - Long QT syndrome (LQTS) is an arrhythmogenic disorder that can lead to sudden death. To date, mutations in 15 LQTS-susceptibility genes have been implicated. However, the genetic cause for approximately 20% of LQTS patients remains elusive. Here, we performed whole-exome sequencing analyses on 59 LQTS and 61 unaffected individuals in 35 families and 138 unrelated LQTS cases, after genetic screening of known LQTS genes. Our systematic analysis of familial cases and subsequent verification by Sanger sequencing identified 92 candidate mutations in 88 genes for 23 of the 35 families (65.7%): these included eleven de novo, five recessive (two homozygous and three compound heterozygous) and seventy-three dominant mutations. Although no novel commonly mutated gene was identified other than known LQTS genes, protein-protein interaction (PPI) network analyses revealed ten new pathogenic candidates that directly or indirectly interact with proteins encoded by known LQTS genes. Furthermore, candidate gene based association studies using an independent set of 138 unrelated LQTS cases and 587 controls identified an additional novel candidate. Together, mutations in these new candidates and known genes explained 37.1% of the LQTS families (13 in 35). Moreover, half of the newly identified candidates directly interact with calmodulin (5 in 11; comparison with all genes; p=0.042). Subsequent variant analysis in the independent set of 138 cases identified 16 variants in the 11 genes, of which 14 were in calmodulin-interacting genes (87.5%). These results suggest an important role of calmodulin and its interacting proteins in the pathogenesis of LQTS. PMID- 26132557 TI - An Optimized Fluorescence-Based Bidimensional Immunoproteomic Approach for Accurate Screening of Autoantibodies. AB - Serological proteome analysis (SERPA) combines classical proteomic technology with effective separation of cellular protein extracts on two-dimensional gel electrophoresis, western blotting, and identification of the antigenic spot of interest by mass spectrometry. A critical point is related to the antigenic target characterization by mass spectrometry, which depends on the accuracy of the matching of antigenic reactivities on the protein spots during the 2D immunoproteomic procedures. The superimposition, based essentially on visual criteria of antigenic and protein spots, remains the major limitation of SERPA. The introduction of fluorescent dyes in proteomic strategies, commonly known as 2D-DIGE (differential in-gel electrophoresis), has boosted the qualitative capabilities of 2D electrophoresis. Based on this 2D-DIGE strategy, we have improved the conventional SERPA by developing a new and entirely fluorescence based bi-dimensional immunoproteomic (FBIP) analysis, performed with three fluorescent dyes. To optimize the alignment of the different antigenic maps, we introduced a landmark map composed of a combination of specific antibodies. This methodological development allows simultaneous revelation of the antigenic, landmark and proteomic maps on each immunoblot. A computer-assisted process using commercially available software automatically leads to the superimposition of the different maps, ensuring accurate localization of antigenic spots of interest. PMID- 26132558 TI - Early menarche and chronic widespread musculoskeletal complaints--Results from the HUNT study. AB - BACKGROUND: There is a predominance of chronic widespread musculoskeletal complaints (WMSC) among women. Previous studies suggest an association between hormonal factors and pain. However, it is not known whether earlier age at menarche is associated with higher prevalence of chronic WMSC. The aim of this study was to investigate the association between age at menarche and chronic WMSC. METHODS: Data from a cross-sectional study of inhabitants >=20 years in Nord-Trondelag County (Helseundersokelsen i Nord-Trondelag -HUNT), conducted in 1995-1997 (HUNT 2) were used. The study population comprised 32,673 women with valid information of age at menarche (exposure) and chronic WMSC (outcome data). RESULTS: In total, 8986 (27.5%) women reported WMSC. The overall prevalence of WMSC was 29.7% among those with menarche <=12 years and 26.7% among those with menarche >12 years. The prevalence of chronic WMSC was consistently higher for those with early age at menarche in all age groups. The crude odds ratio for chronic WMSC, when comparing women with age at menarche <=12 years to women with age at menarche >12 years, was 1.16 (95% CI: 1.10-1.22). The corresponding odds ratio was 1.26 (95% CI: 1.19-1.34) when adjusted for age, education, body mass index (BMI), smoking, alcohol consumption, depression, systolic blood pressure (SBP) and parity. CONCLUSION: In this cross-sectional study, there was an association between early age at menarche and chronic WMSC later in life, but the difference in absolute risk was low (3%). PMID- 26132559 TI - Functional BCL-2 regulatory genetic variants contribute to susceptibility of esophageal squamous cell carcinoma. AB - B-cell lymphoma-2 (BCL-2) prevents apoptosis and its overexpression could promote cancer cell survival. Multiple functional BCL-2 genetic polymorphisms, such as rs2279115, rs1801018 and rs1564483, have been identified previously and might be involved in cancer development through deregulating BCL-2 expression. Therefore, we examined associations between these three polymorphisms and esophageal squamous cell carcinoma (ESCC) susceptibility as well as its biological function in vivo. Genotypes were determined in two independent case-control sets consisted of 1588 ESCC patients and 1600 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. The impact of the rs2279115 polymorphism on BCL-2 expression was detected using esophagus tissues. Our results demonstrated that the BCL-2 rs2279115 AA genotype was significantly associated with decreased ESCC risk compared with the CC genotype (OR = 0.72, 95% CI = 0.57-0.90, P = 0.005), especially in nonsmokers (OR = 0.42, 95% CI = 0.29-0.59, P = 0.001) or nondrinkers (OR = 0.44, 95% CI = 0.32 0.62, P = .002). Genotype-phenotype correlation studies demonstrated that subjects with the rs2279115 CA and AA genotypes had a statistically significant decrease of BCL-2 mRNA expression compared to the CC genotype in both normal and cancerous esophagus tissues. Our results indicate that the BCL-2 rs2279115 polymorphism contributes to ESCC susceptibility in Chinese populations. PMID- 26132560 TI - MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2. AB - Doxorubicin (DOX) is an anthracycline drug with a wide spectrum of antineoplastic activities. However, it causes cardiac cytotoxicity, and this limits its clinical applications. MicroRNA-21 (miR-21) plays a vital role in regulating cell proliferation and apoptosis. While miR-21 is preferentially expressed in adult cardiomyocytes and involved in cardiac development and heart disease, little is known regarding its biological functions in responding to DOX-induced cardiac cytotoxicity. In this study, the effects of DOX on mouse cardiac function and the expression of miR-21 were examined in both mouse heart tissues and rat H9C2 cardiomyocytes. The results showed that the cardiac functions were more aggravated in chronic DOX injury mice compared with acute DOX-injury mice; DOX treatment significantly increased miR-21 expression in both mouse heart tissue and H9C2 cells. Over-expression of miR-21 attenuated DOX-induced apoptosis in cardiamyocytes whereas knocking down its expression increased DOX-induced apoptosis. These gain- and loss- of function experiments showed that B cell translocation gene 2 (BTG2) was a target of miR-21. The expression of BTG2 was significantly decreased both in myocardium and H9C2 cells treated with DOX. The present study has revealed that miR-21 protects mouse myocardium and H9C2 cells against DOX-induced cardiotoxicity probably by targeting BTG2. PMID- 26132562 TI - Analysis of Phenolic Compounds and Antioxidant Activity in Wild Blackberry Fruits. AB - Twenty three different wild blackberry fruit samples were assessed regarding their phenolic profiles and contents (by LC/MS quadrupole time-of-flight (QTOF) and antioxidant activity (ferric reducing ability of plasma (FRAP) and 2,2 azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS)) by two different extraction methods. Thirty four phenolic compounds were detected (8 anthocyanins, 15 flavonols, 3 hydroxycinnamic acids, 6 ellagic acid derivatives and 2 flavones). In samples, where pressurized liquid extraction (PLE) was used for extraction, a greater increase in yields of phenolic compounds was observed, especially in ellagic acid derivatives (max. 59%), flavonols (max. 44%) and anthocyanins (max. 29%), than after extraction by the ultrasonic technique extraction (UAE) method. The content of phenolic compounds was significantly correlated with the antioxidant activity of the analyzed samples. Principal component analysis (PCA) revealed that the PLE method was more suitable for the quantitative extraction of flavonols, while the UAE method was for hydroxycinnamic acids. PMID- 26132561 TI - Eriodictyol Protects Endothelial Cells against Oxidative Stress-Induced Cell Death through Modulating ERK/Nrf2/ARE-Dependent Heme Oxygenase-1 Expression. AB - The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease. PMID- 26132563 TI - Advances in the in Vivo Raman Spectroscopy of Malignant Skin Tumors Using Portable Instrumentation. AB - Raman spectroscopy has emerged as a promising tool for real-time clinical diagnosis of malignant skin tumors offering a number of potential advantages: it is non-intrusive, it requires no sample preparation, and it features high chemical specificity with minimal water interference. However, in vivo tissue evaluation and accurate histopathological classification remain a challenging task for the successful transition from laboratory prototypes to clinical devices. In the literature, there are numerous reports on the applications of Raman spectroscopy to biomedical research and cancer diagnostics. Nevertheless, cases where real-time, portable instrumentations have been employed for the in vivo evaluation of skin lesions are scarce, despite their advantages in use as medical devices in the clinical setting. This paper reviews the advances in real time Raman spectroscopy for the in vivo characterization of common skin lesions. The translational momentum of Raman spectroscopy towards the clinical practice is revealed by (i) assembling the technical specifications of portable systems and (ii) analyzing the spectral characteristics of in vivo measurements. PMID- 26132564 TI - Synthesis and Biological Evaluation of Novel Dehydroabietic Acid Derivatives Conjugated with Acyl-Thiourea Peptide Moiety as Antitumor Agents. AB - A series of dehydroabietic acid (DHAA) acyl-thiourea derivatives were designed and synthesized as potent antitumor agents. The in vitro pharmacological screening results revealed that the target compounds exhibited potent cytotoxicity against HeLa, SK-OV-3 and MGC-803 tumor cell lines, while they showed lower cytotoxicity against HL-7702 normal human river cells. Compound 9n (IC50 = 6.58 +/- 1.11 MUM) exhibited the best antitumor activity against the HeLa cell line and even displayed more potent inhibitory activity than commercial antitumor drug 5-FU (IC50 = 36.58 +/- 1.55 MUM). The mechanism of representative compound 9n was then studied by acridine orange/ethidium bromide staining, Hoechst 33,258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay and flow cytometry, which illustrated that this compound could induce apoptosis in HeLa cells. Cell cycle analysis indicated that compound 9n mainly arrested HeLa cells in the S phase stage. Further investigation demonstrated that compound 9n induced apoptosis of HeLa cells through a mitochondrial pathway. PMID- 26132565 TI - New Hybrid Nanomaterial Based on Self-Assembly of Cyclodextrins and Cobalt Prussian Blue Analogue Nanocubes. AB - Supramolecular self-assembly has been demonstrated to be a useful approach to developing new functional nanomaterials. In this work, we used a cobalt Prussian blue analogue (PBA, Co3[Co(CN)6]2) compound and a beta-cyclodextrin (CD) macrocycle to develop a novel host-guest PBA-CD nanomaterial. The preparation of the functional magnetic material involved the self-assembly of CD molecules onto a PBA surface by a co-precipitation method. According to transmission electronic microscopy results, PBA-CD exhibited a polydisperse structure composed of 3D nanocubes with a mean edge length of 85 nm, which became shorter after CD incorporation. The supramolecular arrangement and structural, crystalline and thermal properties of the hybrid material were studied in detail by vibrational and electronic spectroscopies and X-ray diffraction. The cyclic voltammogram of the hybrid material in a 0.1 mol . L(-1) NaCl supporting electrolyte exhibited a quasi-reversible redox process, attributed to Co2+/Co3+ conversion, with an E1/2 value of 0.46 V (vs. SCE), with higher reversibility observed for the system in the presence of CD. The standard rate constants for PBA and PBA-CD were determined to be 0.07 and 0.13 s(-1), respectively, which suggests that the interaction between the nanocubes and CD at the supramolecular level improves electron transfer. We expect that the properties observed for the hybrid material make it a potential candidate for (bio)sensing designs with a desirable capability for drug delivery. PMID- 26132566 TI - The Effect of Diagnostic Absorbed Doses from 131I on Human Thyrocytes in Vitro. AB - BACKGROUND: Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). MATERIALS AND METHODS: We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. RESULTS: According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. CONCLUSIONS: Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the "thyroid stunning" reduces the NIS protein synthesis. PMID- 26132567 TI - Inferring Invasion History of Red Swamp Crayfish (Procambarus clarkii) in China from Mitochondrial Control Region and Nuclear Intron Sequences. AB - Identifying the dispersal pathways of an invasive species is useful for adopting the appropriate strategies to prevent and control its spread. However, these processes are exceedingly complex. So, it is necessary to apply new technology and collect representative samples for analysis. This study used Approximate Bayesian Computation (ABC) in combination with traditional genetic tools to examine extensive sample data and historical records to infer the invasion history of the red swamp crayfish, Procambarus clarkii, in China. The sequences of the mitochondrial control region and the proPOx intron in the nuclear genome of samples from 37 sites (35 in China and one each in Japan and the USA) were analyzed. The results of combined scenarios testing and historical records revealed a much more complex invasion history in China than previously believed. P. clarkii was most likely originally introduced into China from Japan from an unsampled source, and the species then expanded its range primarily into the middle and lower reaches and, to a lesser extent, into the upper reaches of the Changjiang River in China. No transfer was observed from the upper reaches to the middle and lower reaches of the Changjiang River. Human-mediated jump dispersal was an important dispersal pathway for P. clarkii. The results provide a better understanding of the evolutionary scenarios involved in the rapid invasion of P. clarkii in China. PMID- 26132568 TI - Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates. AB - Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID- 26132569 TI - Echinacoside Induces Apoptosis in Human SW480 Colorectal Cancer Cells by Induction of Oxidative DNA Damages. AB - Echinacoside is a natural compound with potent reactive oxygen species (ROS) scavenging and anti-oxidative bioactivities, which protect cells from oxidative damages. As cancer cells are often under intense oxidative stress, we therefore tested if Echinacoside treatment would promote cancer development. Surprisingly, we found that Echinacoside significantly inhibited the growth and proliferation of a panel of cancer cell lines. Treatment of the human SW480 cancer cells with Echinacoside resulted in marked apoptosis and cell cycle arrest, together with a significant increase in active caspase 3 and cleaved PARP, and upregulation of the G1/S-CDK blocker CDKN1B (p21). Interestingly, immunocytochemistry examination of drug-treated cancer cells revealed that Echinacoside caused a significant increase of intracellular oxidized guanine, 8-oxoG, and dramatic upregulation of the double-strand DNA break (DSB)-binding protein 53BP1, suggesting that Echinacoside induced cell cycle arrest and apoptosis in SW480 cancer cells via induction of oxidative DNA damages. These results establish Echinacoside as a novel chemical scaffold for development of anticancer drugs. PMID- 26132570 TI - Listeria Meningitis Complicating Alemtuzumab Treatment in Multiple Sclerosis- Report of Two Cases. AB - Alemtuzumab, a humanized monoclonal antibody targeting the surface molecule CD52, leads to a rapid depletion of immune cells in the innate and adaptive immune system. In phase 2 and 3 trials in multiple sclerosis (MS), infections have been reported more frequently in alemtuzumab than in interferon beta treated patients. Here we report two patients treated with alemtuzumab for MS developing Listeria meningitis few days after the first infusion cycle. Both patients recovered completely after prompt diagnosis and adequate treatment. Physicians and patients should be aware of this serious, but treatable complication. PMID- 26132572 TI - Inhibition of autophagy in peripheral blood mononuclear cells by vaginal fluid from women with a malignant adnexal mass. AB - Inhibition of autophagy is a characteristic of ovarian cancer. We determined whether inhibition of autophagy by vaginal fluid could provide a non-invasive test for cancer risk stratification in women presenting with an adnexal mass. Vaginal fluid supernatants from 90 women undergoing evaluation for a suspicious adnexal mass were incubated with peripheral blood mononuclear cells (PBMCs) obtained from healthy women under conditions that induce autophagy. Rapamycin, an autophagy inducer, was added to some cultures. After 48 hr the cells were collected, lysed and assayed by ELISA for intracellular p62 concentration. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration is inversely proportional to the extent of autophagy induction. Clinical information including pathological diagnoses was obtained after completion of laboratory studies. Mean p62 levels were 9.4 ng/ml in the 21 women with a subsequent malignant diagnosis, 4.5 ng/ml in the eight women with a borderline tumor diagnosis and 3.6 ng/ml in the 61 women with benign disease (p < 0.0001, malignant vs. others). When rapamycin was added to the vaginal fluid-PBMC co-incubation, p62 levels in samples from women with a malignant diagnosis decreased to 3.3 ng/ml, a level comparable to what was observed with the nonmalignant samples. Vaginal fluid inhibition of autophagy can differentiate between women with malignant and benign adnexal masses. PMID- 26132578 TI - A scoping study to explore the cost-effectiveness of next-generation sequencing compared with traditional genetic testing for the diagnosis of learning disabilities in children. AB - BACKGROUND: Learning disability (LD) is a serious and lifelong condition characterised by the impairment of cognitive and adaptive skills. Some cases of LD with unidentified causes may be linked to genetic factors. Next-generation sequencing (NGS) techniques are new approaches to genetic testing that are expected to increase diagnostic yield. OBJECTIVES: This scoping study focused on the diagnosis of LD in children and the objectives were to describe current pathways that involve the use of genetic testing; collect stakeholder views on the changes in service provision that would need to be put in place before NGS could be used in clinical practice; describe the new systems and safeguards that would need to be put in place before NGS could be used in clinical practice; and explore the cost-effectiveness of using NGS compared with conventional genetic testing. METHODS: A research advisory group was established. This group provided ongoing support by e-mail and telephone through the lifetime of the study and also contributed face-to-face through a workshop. A detailed review of published studies and reports was undertaken. In addition, information was collected through 33 semistructured interviews with key stakeholders. RESULTS: NGS techniques consist of targeted gene sequencing, whole-exome sequencing (WES) and whole-genome sequencing (WGS). Targeted gene panels, which are the least complex, are in their infancy in clinical settings. Some interviewees thought that during the next 3-5 years targeted gene panels would be superseded by WES. If NGS technologies were to be fully introduced into clinical practice in the future a number of factors would need to be overcome. The main resource-related issues pertaining to service provision are the need for additional computing capacity, more bioinformaticians, more genetic counsellors and also genetics-related training for the public and a wide range of staff. It is also considered that, as the number of children undergoing genetic testing increases, there will be an increase in demand for information and support for families. The main issues relating to systems and safeguards are giving informed consent, sharing unanticipated findings, developing ethical and other frameworks, equity of access, data protection, data storage and data sharing. There is little published evidence on the cost-effectiveness of NGS technologies. The major barriers to determining cost-effectiveness are the uncertainty around diagnostic yield, the heterogeneity of diagnostic pathways and the lack of information on the impact of a diagnosis on health care, social care, educational support needs and the wider family. Furthermore, as NGS techniques are currently being used only in research, costs and benefits to the NHS are unclear. CONCLUSIONS: NGS technologies are at an early stage of development and it is too soon to say whether they can offer value for money to the NHS as part of the LD diagnostic process. Substantial organisational changes, as well as new systems and safeguards, would be required if NGS technologies were to be introduced into NHS clinical practice. Considerable further research is required to establish whether using NGS technologies to diagnose learning disabilities is clinically effective and cost effective. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26132579 TI - Impact of a Hurricane Shelter Viral Gastroenteritis Outbreak on a Responding Medical Team. AB - Introduction In late October of 2012, Hurricane Sandy struck the northeast United States and shelters were established throughout the impacted region. Numerous cases of infectious viral gastroenteritis occurred in several of these shelters. Such outbreaks are common and have been well described in the past. Early monitoring for, and recognition of, the outbreak allowed for implementation of aggressive infection control measures. However, these measures required intensive medical response team involvement. Little is known about how such outbreaks affect the medical teams responding to the incident. Hypothesis/Problem Describe the impact of an infectious viral gastroenteritis outbreak within a single shelter on a responding medical team. METHODS: The number of individuals staying in the single shelter each night (as determined by shelter staff) and the number of patients treated for symptoms of viral gastroenteritis were recorded each day. On return from deployment, members of a single responding medical team were surveyed to determine how many team members became ill during, or immediately following, their deployment. RESULTS: The shelter population peaked on November 5, 2012 with 811 individuals sleeping in the shelter. The first patients presented to the shelter clinic with symptoms of viral gastroenteritis on November 4, 2012, and the last case was seen on November 21, 2012. A total of 64 patients were treated for nausea, vomiting, or diarrhea over the 17-day period. A post-deployment survey was sent to 66 deployed medical team members and 45 completed the survey. Twelve (26.7%) of the team members who responded to the survey experienced symptoms of probable viral gastroenteritis. Team members reported onset of symptoms during deployment as well as after returning home. Symptoms started on days 4-8, 8-14, on the trip home, and after returning home in four, four, two, and two team members, respectively. CONCLUSION: Medical teams providing shelter care during viral gastroenteritis outbreaks are susceptible to contracting the virus while caring for patients. When responding to similar incidents in the future, teams should not only be ready to implement aggressive infectious control measures but also be prepared to care for team members who become ill. PMID- 26132580 TI - Correction: The MAT Locus Genes Play Different Roles in Sexual Reproduction and Pathogenesis in Fusarium graminearum. PMID- 26132581 TI - Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse? AB - BACKGROUND: Effective fetal growth requires adequate maternal nutrition coupled to active transport of nutrients across the placenta, which, in turn requires ATP. Epidemiological and experimental evidence has shown that impaired maternal nutrition in utero results in an adverse postnatal phenotype for the offspring. Placental mitochondrial function might link maternal food intake to fetal growth since impaired placental ATP production, in response to poor maternal nutrition, could be a pathway linking maternal food intake to reduced fetal growth. METHOD: We assessed the effects of maternal diet on placental water content, ATP levels and mitochondrial DNA (mtDNA) content in mice at embryonic (E) day 18 (E18). Females maintained on either low- (LPD) or normal- (NPD) protein diets were mated with NPD males. RESULTS: Fetal dry weight and placental efficiency (embryo/placental fresh weight) were positively correlated (r = 0.53, P = 0.0001). Individual placental dry weight was reduced by LPD (P = 0.003), as was the expression of amino acid transporter Slc38a2 and of growth factor Igf2. Placental water content, which is regulated by active transport of solutes, was increased by LPD (P = 0.0001). However, placental ATP content was also increased (P = 0.03).To investigate the possibility of an underlying mitochondrial stress response, we studied cultured human trophoblast cells (BeWos). High throughput imaging showed that amino acid starvation induces changes in mitochondrial morphology that suggest stress-induced mitochondrial hyperfusion. This is a defensive response, believed to increase mitochondrial efficiency, that could underlie the increase in ATP observed in placenta. CONCLUSIONS: These findings reinforce the pathophysiological links between maternal diet and conceptus mitochondria, potentially contributing to metabolic programming. The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism. This may extend to post-implantation trophoblast responses to nutrition. PMID- 26132582 TI - The Possible Mechanisms of the Impaired Insulin Secretion in Hypothyroid Rats. AB - Although the insulin secretion deficit in hypothyroid male rats has been documented, the underling mechanisms of the effect of hypothyroidism on insulin secretion are not clear. Isolated islets of the PTU-induced hypothyroid and control rats were exposed to glibenclamide, acetylcholine, and nifedipine in the presence of glucose concentrations of 2.8 or 8.3 and 16.7 mmol/L. Glucokinase and hexokinase specific activity, glucokinase content, and glucose transporter 2 protein expression were also determined in the isolated islets. Isolated islets from the hypothyroid rats showed a defect in insulin secretion in response to high glucose. In the presence of glibenclamide or acetylcholine, the isolated islets from the hypothyroid and control rats stimulated by glucose concentration of 16.7 mmol/L secreted similar amounts of insulin. In the presence of glucose concentrations of 8.3 mmol/L and 16.7 mmol/L, nifedipine was able to diminish insulin secretion from isolated islets of both groups, indicating that probably the defect may not arise from L type calcium channels or the steps beyond depolarization or the elements involved in the acetylcoline signaling pathway. Glucokinase content and hexokinase specific activity were also the same in the control and hypothyroid groups. On the other hand, glucokinase specific activity and glucose transporter 2 protein expression were significantly (p<0.001 and p<0.01 respectively) lower in the islets isolated from the hypothyroid rats (6.50 +/- 0.46 mU/min/mg protein and 0.55 +/- 0.09 arbitrary unit) compared to the controls (10.93 +/- 0.83 mU/min/mg protein and 0.98 +/- 0.07 arbitrary unit) respectively. In conclusion, the results of this study indicated that hypothyroidism reduced insulin secretion from isolated pancreatic islets, which confirms the finding of the previous studies; in addition, the insulin secretion deficit observed in hypothyroid rats may arise from the abnormalities in some parts of the glucose sensor apparatus of the pancreatic islets including glucokinase activity and glucose transporter 2 protein expression. PMID- 26132583 TI - Salivary Matrix Metalloproteinase-8 and -9 and Myeloperoxidase in Relation to Coronary Heart and Periodontal Diseases: A Subgroup Report from the PAROKRANK Study (Periodontitis and Its Relation to Coronary Artery Disease). AB - BACKGROUND AND OBJECTIVE: Matrix metalloproteinase (MMP) -8, -9 and myeloperoxidase (MPO) are inflammatory mediators. The potential associations between MMP-8, -9, MPO and their abilities to reflect cardiovascular risk remains to be evaluated in saliva. The objective of this study was to investigate the levels and associations of salivary MMP-8, -9, MPO and tissue inhibitors of metalloproteinase (TIMP)-1 in myocardial infarction (MI) patients and controls with or without periodontitis. MATERIALS AND METHODS: 200 patients with a first MI admitted to coronary care units in Sweden from May 2010 to December 2011 and 200 controls matched for age, gender, residential area and without previous MI were included. Dental examination and saliva sample collection was performed 6-10 weeks after the MI in patients and at baseline in controls. The biomarkers MMP 8, -9, MPO and TIMP-1 were analyzed by time-resolved immunofluorescence assay (IFMA), Western blot and Enzyme-Linked ImmunoSorbent Assay (ELISA). RESULTS: After compensation for gingivitis, gingival pockets and smoking, the mean salivary levels of MMP-8 (543 vs 440 ng/mL, p = 0.003) and MPO (1899 vs 1637 ng/mL, p = 0.02) were higher in non-MI subjects compared to MI patients. MMP-8, 9 and MPO correlated positively with clinical signs of gingival/periodontal inflammation while TIMP-1 correlated mainly negatively with these signs. The levels of latent and active forms of MMP-8 did not differ between the MI and non MI groups. Additionally, MMP-8, MPO levels and MMP-8/TIMP-1 ratio were significantly higher in men compared to women with MI. CONCLUSIONS: This study shows that salivary levels of the analyzed biomarkers are associated with periodontal status. However, these biomarkers could not differentiate between patients with or without a MI. These findings illustrate the importance to consider the influence of oral conditions when analyzing levels of inflammatory salivary biomarkers. PMID- 26132584 TI - The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis. AB - BACKGROUND: In India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects. RESULTS: We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases) between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India. PMID- 26132586 TI - Three-Year Outcomes of Bariatric Surgery vs Lifestyle Intervention for Type 2 Diabetes Mellitus Treatment: A Randomized Clinical Trial. AB - IMPORTANCE: Questions remain about the role and durability of bariatric surgery for type 2 diabetes mellitus (T2DM). OBJECTIVE: To compare the remission of T2DM following surgical and nonsurgical treatments. DESIGN, SETTING, AND PARTICIPANTS: In this 3-arm randomized clinical trial conducted at the University of Pittsburgh Medical Center from October 1, 2009, to June 26, 2014, in Pittsburgh, Pennsylvania, outcomes were assessed 3 years after treating 61 obese participants aged 25 to 55 years with T2DM. Analysis was conducted with an intent-to-treat population. INTERVENTIONS: Participants were randomized to either an intensive lifestyle weight loss intervention for 1 year followed by a low-level lifestyle intervention for 2 years or surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) followed by low-level lifestyle intervention in years 2 and 3. MAIN OUTCOMES AND MEASURES: Primary end points were partial and complete T2DM remission and secondary end points included diabetes medications and weight change. RESULTS: Body mass index (calculated as weight in kilograms divided by height in meters squared) was less than 35 for 26 participants (43%), 50 (82%) were women, and 13 (21%) were African American. Mean (SD) values were 100.5 (13.7) kg for weight, 47.3 (6.6) years for age, 7.8% (1.9%) for hemoglobin A1c level, and 171.3 (72.5) mg/dL for fasting plasma glucose level. Partial or complete T2DM remission was achieved by 40% (n = 8) of RYGB, 29% (n = 6) of LAGB, and no intensive lifestyle weight loss intervention participants (P = .004). The use of diabetes medications was reduced more in the surgical groups than the lifestyle intervention-alone group, with 65% of RYGB, 33% of LAGB, and none of the intensive lifestyle weight loss intervention participants going from using insulin or oral medication at baseline to no medication at year 3 (P < .001). Mean (SE) reductions in percentage of body weight at 3 years were the greatest after RYGB at 25.0% (2.0%), followed by LAGB at 15.0% (2.0%) and lifestyle treatment at 5.7% (2.4%) (P < .01). CONCLUSIONS AND RELEVANCE: Among obese participants with T2DM, bariatric surgery with 2 years of an adjunctive low-level lifestyle intervention resulted in more disease remission than did lifestyle intervention alone. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01047735. PMID- 26132587 TI - Facile and Efficient Preparation of Tri-component Fluorescent Glycopolymers via RAFT-controlled Polymerization. AB - Synthetic glycopolymers are instrumental and versatile tools used in various biochemical and biomedical research fields. An example of a facile and efficient synthesis of well-controlled fluorescent statistical glycopolymers using reversible addition-fragmentation chain-transfer (RAFT)-based polymerization is demonstrated. The synthesis starts with the preparation of beta-galactose containing glycomonomer 2-lactobionamidoethyl methacrylamide obtained by reaction of lactobionolactone and N-(2-aminoethyl) methacrylamide (AEMA). 2 Gluconamidoethyl methacrylamide (GAEMA) is used as a structural analog lacking a terminal beta-galactoside. The following RAFT-mediated copolymerization reaction involves three different monomers: N-(2-hydroxyethyl) acrylamide as spacer, AEMA as target for further fluorescence labeling, and the glycomonomers. Tolerant of aqueous systems, the RAFT agent used in the reaction is (4-cyanopentanoic acid)-4 dithiobenzoate. Low dispersities (<=1.32), predictable copolymer compositions, and high reproducibility of the polymerizations were observed among the products. Fluorescent polymers are obtained by modifying the glycopolymers with carboxyfluorescein succinimidyl ester targeting the primary amine functional groups on AEMA. Lectin-binding specificities of the resulting glycopolymers are verified by testing with corresponding agarose beads coated with specific glycoepitope recognizing lectins. Because of the ease of the synthesis, the tight control of the product compositions and the good reproducibility of the reaction, this protocol can be translated towards preparation of other RAFT-based glycopolymers with specific structures and compositions, as desired. PMID- 26132588 TI - Y2O3:Yb,Er@mSiO2-Cu(x)S double-shelled hollow spheres for enhanced chemo /photothermal anti-cancer therapy and dual-modal imaging. AB - Multifunctional composites have gained significant interest due to their unique properties which show potential in biological imaging and therapeutics. However, the design of an efficient combination of multiple diagnostic and therapeutic modes is still a challenge. In this contribution, Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) with up-conversion fluorescence have been successfully prepared through a facile integrated sacrifice template method, followed by a calcination process. It is found that the double-shelled structure with large specific surface area and uniform shape is composed of an inner shell of luminescent Y2O3:Yb,Er and an outer mesoporous silica shell. Ultra small Cu(x)S nanoparticles (about 2.5 nm) served as photothermal agents, and a chemotherapeutic agent (doxorubicin, DOX) was then attached onto the surface of mesoporous silica, forming a DOX-DSHS-Cu(x)S composite. The composite exhibits high anti-cancer efficacy due to the synergistic photothermal therapy (PTT) induced by the attached Cu(x)S nanoparticles and the enhanced chemotherapy promoted by the heat from the Cu(x)S-based PTT when irradiated by 980 nm near infrared (NIR) light. Moreover, the composite shows excellent in vitro and in vivo X-ray computed tomography (CT) and up-conversion fluorescence (UCL) imaging properties owing to the doped rare earth ions, thus making it possible to achieve the target of imaging-guided synergistic therapy. PMID- 26132589 TI - Antipsychotic Use in Youth Without Psychosis: A Double-edged Sword. PMID- 26132585 TI - The Discovery of Novel Biomarkers Improves Breast Cancer Intrinsic Subtype Prediction and Reconciles the Labels in the METABRIC Data Set. AB - BACKGROUND: The prediction of breast cancer intrinsic subtypes has been introduced as a valuable strategy to determine patient diagnosis and prognosis, and therapy response. The PAM50 method, based on the expression levels of 50 genes, uses a single sample predictor model to assign subtype labels to samples. Intrinsic errors reported within this assay demonstrate the challenge of identifying and understanding the breast cancer groups. In this study, we aim to: a) identify novel biomarkers for subtype individuation by exploring the competence of a newly proposed method named CM1 score, and b) apply an ensemble learning, as opposed to the use of a single classifier, for sample subtype assignment. The overarching objective is to improve class prediction. METHODS AND FINDINGS: The microarray transcriptome data sets used in this study are: the METABRIC breast cancer data recorded for over 2000 patients, and the public integrated source from ROCK database with 1570 samples. We first computed the CM1 score to identify the probes with highly discriminative patterns of expression across samples of each intrinsic subtype. We further assessed the ability of 42 selected probes on assigning correct subtype labels using 24 different classifiers from the Weka software suite. For comparison, the same method was applied on the list of 50 genes from the PAM50 method. CONCLUSIONS: The CM1 score portrayed 30 novel biomarkers for predicting breast cancer subtypes, with the confirmation of the role of 12 well-established genes. Intrinsic subtypes assigned using the CM1 list and the ensemble of classifiers are more consistent and homogeneous than the original PAM50 labels. The new subtypes show accurate distributions of current clinical markers ER, PR and HER2, and survival curves in the METABRIC and ROCK data sets. Remarkably, the paradoxical attribution of the original labels reinforces the limitations of employing a single sample classifiers to predict breast cancer intrinsic subtypes. PMID- 26132590 TI - Influence of high dose of phytase and an emulsifier on performance, apparent metabolisable energy and nitrogen retention in broilers fed on diets containing soy oil or tallow. AB - The effects of high dose of microbial phytase and an emulsifier on the performance, apparent metabolisable energy (AME) and nitrogen (N) retention in broilers fed on diets containing different fat sources were examined in a 5-week trial. Two fat sources (soy oil and tallow), two inclusion levels of E. coli phytase (500 or 1000 phytase units (FTU)/kg diet) and two inclusion levels of lysolecithin emulsifier (0 or 3.5 g/kg of diet) were evaluated in a 2 * 2 * 2 factorial arrangement of treatments. Throughout the 5-week trial, soy oil supplementation improved weight gain and feed per gain compared with tallow, but had no effect on feed intake. The high dose of phytase increased the weight gain and feed intake and lowered the feed per gain during d 1-21, but had no effect on performance parameters over the whole trial period. An effect of emulsifier was observed for feed intake during d 1-21 and over the whole trial period. Addition of emulsifier increased feed intake compared with diets without emulsifier. During weeks 1, 2, 3 and 5, birds fed on soy oil-based diets had higher nitrogen corrected AME (AMEN) compared with those fed on tallow-based diets. During weeks 2, 3 and 5, the effect of phytase was significant for AMEN, with the high dose increasing the AMEN. During week 2, AMEN was increased with emulsifier addition. During weeks 1, 2, 3 and 5, birds fed on soy oil-based diets had higher fat retention compared with those fed on tallow-based diets. The high dose of phytase improved the retention of fat during week 5 and the addition of emulsifier resulted in higher fat retention during week 1. During weeks 2, 3 and 5, an interaction between fat source * phytase * emulsifier was observed for N retention. In soy oil-based diets, emulsifier plus 1000 FTU/kg phytase increased N retention compared with other groups, while in tallow-based diets, emulsifier addition increased N retention in diets with 500 FTU/kg, but not in 1000 FTU/kg diet. Overall, the present data suggest that the dietary fat source influenced performance, AMEN and fat retention in broiler chickens. There is opportunity to improve bird performance during d 1-21, AMEN and fat retention with higher doses of microbial phytase. Addition of the emulsifier increased the AMEN during week 2 and tract retention of fat during week 1, but this effect was not translated into improvements in performance. PMID- 26132591 TI - Reconstruction and validation of a constraint-based metabolic network model for bone marrow-derived mesenchymal stem cells. AB - OBJECTIVES: Over recent years, constraint-based modelling of metabolic networks has become increasingly popular; the models are suitable for system-level modelling of cell physiology. The goal of the present work was to reconstruct a constraint-based metabolic network model of bone marrow-derived mesenchymal stem cells (BMMSCs). MATERIALS AND METHODS: To reconstruct a BMMSC-specific metabolic model, transcriptomic data of BMMSCs, and additionally, the human generic metabolic network model (Recon1) were used. Then, using the mCADRE algorithm, a draft metabolic network was reconstructed. Literature and proteomic data were subsequently used to refine and improve the draft. From this, iMSC1255 was derived to be the metabolic network model of BMMSCs. RESULTS: iMSC1255 has 1255 genes, 1850 metabolites and 2288 reactions. After including additional constraints based on previously reported experimental results, our model successfully predicted BMMSC growth rate and metabolic phenotypes. CONCLUSIONS: Here, iMSC1255 is introduced to be the metabolic network model of bone marrow derived mesenchymal stem cells. Based on current knowledge, this is the first report on genome-scale reconstruction and validation of a stem cell metabolic network model. PMID- 26132592 TI - Development of Cutting and Suction Device with Twist Blade Screw for Minimally Invasive Surgery: Evaluation of Suction Performance. AB - In this study, we aim to develop a narrow-diameter and long-bore device for minimally invasive surgery that achieves the simultaneous cutting and suction of body tissue such as the diseased part of an organ. In this paper, we propose a screw made of a thin metal plate, and we developed a prototype device using this screw. For smooth operation, the suction performance must be superior to the cutting performance. Therefore, we performed experiments and evaluated the suction performance of the developed device assuming the crushed tissue pieces correspond to a highly viscous fluid. From the results, we confirmed that the suction volume is almost proportional to the rotation speed of the screw in the low speed range, and the device has an upper limit of suction volume at a certain rotation speed. Considering practical use, its proportional speed range is suitable for the device controllability of cutting and suction volume, and the size of the device tip needs to be 1 mm or more. Based on these conditions, we are planning to examine the shape of the cutting edge for realizing efficient cutting and suction and we will complete the device. PMID- 26132593 TI - High Catalytic Activity of Amorphous Ir-Pi for Oxygen Evolution Reaction. AB - Large-scale production of hydrogen gas by water electrolysis is hindered by the sluggish kinetics of oxygen evolution reaction (OER) at the anode. The development of a highly active and stable catalyst for OER is a challenging task. Electrochemically prepared amorphous metal-based catalysts have gained wide attention after the recent discovery of a cobalt-phosphate (Co-Pi) catalyst. Herein, an amorphous iridium-phosphate (Ir-Pi) is investigated as an oxygen evolution catalyst. The catalyst is prepared by the anodic polarization of carbon paper electrodes in neutral phosphate buffer solutions containing IrCl3. The Ir Pi film deposited on the substrate has significant amounts of phosphate and Ir centers in an oxidation state higher than +4. Phosphate plays a significant role in the deposition of the catalyst and also in its activity toward OER. The onset potential of OER on the Ir-Pi is about 150 mV lower in comparison with the Co-Pi under identical experimental conditions. Thus, Ir-Pi is a promising catalyst for electrochemical oxidation of water. PMID- 26132594 TI - Impaired leucocyte activation is underlining the lower thrombotic risk of essential thrombocythaemia patients with CALR mutations as compared with those with the JAK2 mutation. PMID- 26132595 TI - High-flow oxygen, a primary oxygenation technique for endolaryngeal airway surgery: Our experience with 10 patients. PMID- 26132597 TI - Topical tacrolimus for atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) (or atopic eczema) is a chronic inflammatory skin condition that affects children and adults and has an important impact on quality of life. Topical corticosteroids (TCS) are the first-line therapy for this condition; however, they can be associated with significant adverse effects when used chronically. Tacrolimus ointment (in its 2 manufactured strengths of 0.1% and 0.03%) might be an alternative treatment. Tacrolimus, together with pimecrolimus, are drugs called topical calcineurin inhibitors (TCIs). OBJECTIVES: To assess the efficacy and safety of topical tacrolimus for moderate and severe atopic dermatitis compared with other active treatments. SEARCH METHODS: We searched the following databases up to 3 June 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 5, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), and the Global Resource of Eczema Trials (GREAT database). We searched six trials registers and checked the bibliographies of included studies for further references to relevant trials. We contacted specialists in the field for unpublished data.A separate search for adverse effects of topical tacrolimus was undertaken in MEDLINE and EMBASE on 30 July 2013. We also scrutinised the U.S. Food and Drug Administration (FDA) websites for adverse effects information. SELECTION CRITERIA: All randomised controlled trials (RCTs) of participants with moderate to severe atopic dermatitis (both children and adults) using topical tacrolimus at any dose, course duration, and follow-up time compared with other active treatments. DATA COLLECTION AND ANALYSIS: Two authors independently screened and examined the full text of selected studies for compliance with eligibility criteria, risk of bias, and data extraction. Our three prespecified primary outcomes were physician's assessment, participant's self-assessment of improvement, and adverse effects. Our secondary outcomes included assessment of improvement of the disease by validated or objective measures, such as SCORAD (SCORing Atopic Dermatitis), the EASI (Eczema Area and Severity Index), and BSA (Body Surface Area) scores. MAIN RESULTS: We included 20 studies, with 5885 participants. The variability of drug doses, outcomes, and follow-up periods made it difficult to carry out meta analyses.A single trial showed that tacrolimus 0.1% was better than low-potency TCS by the physician's assessment (risk ratio (RR) 3.09, 95% confidence interval (CI) 2.14 to 4.45, 1 study, n = 371, moderate-quality evidence). It was also marginally better than low-potency TCS on face and neck areas and moderate potency TCS on the trunk and extremities by the physician's assessment (RR 1.32, 95% CI 1.17 to 1.49, 1 study, n = 972, moderate level of evidence) and for some of the secondary outcomes. Compared with pimecrolimus 1%, people treated with tacrolimus were almost twice as likely to improve by the physician's assessment (RR 1.80, 95% CI 1.34 to 2.42, 2 studies, n = 506, moderate quality of evidence). Compared with the lower concentration of 0.03%, the tacrolimus 0.1% formulation reduced the risk of not having an improvement by 18% as evaluated by the physician's assessment (RR 0.82, 95% CI 0.72 to 0.92, 6 studies, n = 1640, high quality evidence). Tacrolimus 0.1% compared with moderate-to-potent TCS showed no difference by the physician's assessment, and 2 secondary outcomes (1 study, 377 participants) and a marginal benefit favouring tacrolimus 0.1% was found by the participant's assessment (RR 1.21, 95% CI 1.13 to 1.29, 1 study, n = 974, low quality of evidence) and SCORAD.Based on data from 2 trials, tacrolimus 0.03% was superior to mild TCS for the physician's assessment (RR 2.58, 95% CI 1.96 to 3.38, 2 studies, n = 790, moderate-quality evidence) and the participant's self assessment (RR 1.64, 95% CI 1.41 to 1.90, 1 study, n = 416, moderate quality of evidence). One trial showed moderate benefit of tacrolimus 0.03% compared with pimecrolimus 1% on the physician's assessment (RR 1.42, 95% CI 1.02 to 1.98, 1 study, n = 139, low-quality evidence), but the effects were equivocal when evaluating BSA. In the comparison of tacrolimus 0.03% with moderate-to-potent corticosteroids, no difference was found in most of the outcomes measured (including physician's and participant's assessment and also for the secondary outcomes), but in two studies, a marginal benefit favouring the corticosteroid group was found for the EASI and BSA scores.Burning was more frequent in those using calcineurin inhibitors than those using corticosteroid tacrolimus 0.03% (RR 2.48, 95% CI 1.96 to 3.14, 5 studies, 1883 participants, high-quality evidence), but no difference was found for skin infections. Symptoms observed were mild and transient. The comparison between the two calcineurin inhibitors (pimecrolimus and tacrolimus) showed the same overall incidence of adverse events, but with a small difference in the frequency of local effects.Serious adverse events were rare; occurred in both the tacrolimus and corticosteroid groups; and in most cases, were considered to be unrelated to the treatment. No cases of lymphoma were noted in the included studies nor in the non-comparative studies. Cases were only noted in spontaneous reports, cohorts, and case-control studies. Systemic absorption was rarely detectable, only in low levels, and this decreased with time. Exception is made for diseases with severe barrier defects, such as Netherton's syndrome, lamellar ichthyosis, and a few others, with case reports of a higher absorption. We evaluated clinical trials; case reports; and in vivo, in vitro, and animal studies; and didn't find any evidence that topical tacrolimus could cause skin atrophy. AUTHORS' CONCLUSIONS: Tacrolimus 0.1% was better than low-potency corticosteroids, pimecrolimus 1%, and tacrolimus 0.03%. Results were equivocal when comparing both dose formulations to moderate-to-potent corticosteroids. Tacrolimus 0.03% was superior to mild corticosteroids and pimecrolimus. Both tacrolimus formulations seemed to be safe, and no evidence was found to support the possible increased risk of malignancies or skin atrophy with their use. The reliability and strength of the evidence was limited by the lack of data; thus, findings of this review should be interpreted with caution. We did not evaluate costs. PMID- 26132598 TI - Mercury(II) determination in commercial cosmetics and local Thai traditional medicines by flow injection spectrophotometry. AB - OBJECTIVE: The proposed method was developed for the enhancement of sensitivity for Hg(II) determination using dithizone by adding SDS in the presence of ascorbic acid in sulphuric acid medium. METHOD: The method was based on the reaction between Hg(II) and 1,5-diphenylthiocarbazone (dithizone), in the presence of sodium dodecyl sulphate (SDS) as an anionic surfactant (to avoid solvent extraction) and ascorbic acid in a slightly acidic medium resulting in a soluble orange coloured Hg(II)-dithizone complex which gave the maximum absorption at 490 nm. No extraction system was required in this method. RESULT: Under the optimum conditions, a linear calibration graph was obtained over the concentration range of 0.05-1.50 MUg mL(-1). The method was characterized by a limit of detection (LOD, defined as 3sigma) and limit of quantification (LOQ, defined as 10sigma) of 0.03 and 0.14 MUg mL(-1), respectively. The relative standard deviations for replicate injection were 1.32 and 0.78% (n = 11) for 0.05 and 0.20 MUg mL(-1) of Hg(II) standard solutions, respectively. The developed method has been satisfactorily applied for Hg(II) determination in commercial cosmetics and local Thai traditional medicines. Results obtained by the proposed method are compared favourably with those analysed by ICP-MS. CONCLUSION: Enhancement of sensitivity and rapidity for Hg(II) assay by FIA could be achieved by adding SDS in ascorbic acid. The method would be useful for routine analysis of Hg(II) in real samples. PMID- 26132599 TI - A multiparental cross population for mapping QTL for agronomic traits in durum wheat (Triticum turgidum ssp. durum). AB - Multiparental cross designs for mapping quantitative trait loci (QTL) provide an efficient alternative to biparental populations because of their broader genetic basis and potentially higher mapping resolution. We describe the development and deployment of a recombinant inbred line (RIL) population in durum wheat (Triticum turgidum ssp. durum) obtained by crossing four elite cultivars. A linkage map spanning 2664 cM and including 7594 single nucleotide polymorphisms (SNPs) was produced by genotyping 338 RILs. QTL analysis was carried out by both interval mapping on founder haplotype probabilities and SNP bi-allelic tests for heading date and maturity date, plant height and grain yield from four field experiments. Sixteen QTL were identified across environments and detection methods, including two yield QTL on chromosomes 2BL and 7AS, with the former mapped independently from the photoperiod response gene Ppd-B1, while the latter overlapped with the vernalization locus VRN-A3. Additionally, 21 QTL with environment-specific effects were found. Our results indicated a prevalence of environment-specific QTL with relatively small effect on the control of grain yield. For all traits, functionally different QTL alleles in terms of direction and size of genetic effect were distributed among parents. We showed that QTL results based on founder haplotypes closely matched functional alleles at known heading date loci. Despite the four founders, only 2.1 different functional haplotypes were estimated per QTL, on average. This durum wheat population provides a mapping resource for detailed genetic dissection of agronomic traits in an elite background typical of breeding programmes. PMID- 26132600 TI - Common Data Elements for Muscle Biopsy Reporting. AB - CONTEXT: There is no current standard among myopathologists for reporting muscle biopsy findings. The National Institute of Neurological Disorders and Stroke has recently launched a common data element (CDE) project to standardize neuromuscular data collected in clinical reports and to facilitate their use in research. OBJECTIVE: To develop a more-uniform, prospective reporting tool for muscle biopsies, incorporating the elements identified by the CDE project, in an effort to improve reporting and educational resources. DESIGN: The variation in current biopsy reporting practice was evaluated through a study of 51 muscle biopsy reports from self-reported diagnoses of genetically confirmed or undiagnosed muscle disease from the Congenital Muscle Disease International Registry. Two reviewers independently extracted data from deidentified reports and entered them into the revised CDE format to identify what was missing and whether or not information provided on the revised CDE report (complete/incomplete) could be successfully interpreted by a neuropathologist. RESULTS: Analysis of the data highlighted showed (1) inconsistent reporting of key clinical features from referring physicians, and (2) considerable variability in the reporting of pertinent positive and negative histologic findings by pathologists. CONCLUSIONS: We propose a format for muscle-biopsy reporting that includes the elements in the CDE checklist and a brief narrative comment that interprets the data in support of a final interpretation. Such a format standardizes cataloging of pathologic findings across the spectrum of muscle diseases and serves emerging clinical care and research needs with the expansion of genetic-testing therapeutic trials. PMID- 26132602 TI - A Swiss Longitudinal Study of the Prevalence of, and Overlap Between, Sexual Problems in Men and Women Aged 20 to 50 Years Old. AB - The aim of this study was to obtain data on the development and course of sexual problems and their interrelationships by investigating a representative sample of men and women over a period of 30 years. A representative sample of 299 women selected from the complete electoral register and 292 men selected from screening lists for military service in Zurich, Switzerland, answered questions about their sexuality as part of a series of seven interviews between ages 20 (1979) and 50 (2008). Of the initial sample of 591 participants, 43% (57% of them male) were lost to follow-up. Interviews were conducted using the Structured Psychopathological Interview and Rating of the Social Consequences of Psychological Disturbances for Epidemiology (SPIKE), a semistructured interview. Sexual problems were identified on the basis of the study participants' self appraisal. One-year prevalence rates, lifetime risks, and overlap of functional, emotional, and sexual desire problems in men and women were evaluated. The findings confirmed higher lifetime risks in women than in men for any sexual problem (females 67.0%; males 46.0%) and for functional (39.3%; 22.1%), emotional (35.7%; 15.9%), and sexual desire problems (51.6%; 33.3%). While in general men's sexual problems increased with age, no such association was observed in women. The overlap of all three problems (functional, emotional, and sexual desire) was reported by 16.9% of women but only 5.0% of men. Although there are commonalities, the type but also the development and, in particular, the overlap of sexual problems in women and men are markedly different. PMID- 26132603 TI - Effects of Issue Involvement and Framing of a Responsible Drinking Message on Attitudes, Intentions, and Behavior. AB - To decrease the prevalence and the amount of alcohol consumption among students, health messages advocating responsible alcohol behavior can be used. However, it is unclear whether responsible drinking messages are most effective when they use a gain frame, presenting the advantages of responsible drinking, or a loss frame, presenting the disadvantages of irresponsible drinking. This study tests the effects of framing and the moderating role of involvement with the issue of responsible drinking. A three-wave, between-subjects, experimental study was conducted, in which participants (N = 90) were exposed to either a gain- or loss framed message about responsible drinking behavior at Wave 2. At all three waves, attitudes, intentions and behavior toward responsible drinking were measured. Results showed that for participants with low issue- involvement, a gain frame led to more positive attitudes and intentions toward responsible alcohol use, whereas a loss frame did not have any effects for them. For participants with high issue involvement, a loss frame led to more positive attitudes and intentions toward responsible alcohol use, whereas a gain frame did not have an effect on attitude and only a delayed effect on intention. However, there were no effects of frame and issue involvement on adhering to the guideline of responsible alcohol use and average drinking behavior. PMID- 26132601 TI - Cancer as the Disintegration of Robustness: Population-Level Variance in Gene Expression Identifies Key Differences Between Tobacco- and HPV-Associated Oropharyngeal Carcinogenesis. AB - CONTEXT: Oropharyngeal squamous cell carcinoma is associated both with tobacco use and with human papillomavirus (HPV) infection. It is argued that carcinogen driven tumorigenesis is a distinct disease from its virally driven counterpart. We hypothesized that tumorigenesis is the result of a loss of genotypic robustness resulting in an increase in phenotypic variation in tumors compared with adjacent histologically normal tissues, and that carcinogen-driven tumorigenesis results in greater variation than its virally driven counterpart. OBJECTIVES: To examine the loss of robustness in carcinogen-driven and virally driven oropharyngeal squamous cell carcinoma samples, and to identify potential pathways involved. DESIGN: We used coefficients of variation for messenger RNA and microRNA expression to measure the loss of robustness in oropharyngeal squamous cell carcinoma samples. Tumors were compared with matched normal tissues, and were further categorized by HPV and patient smoking status. Weighted gene coexpression networks were constructed for genes with highly variable expression among the HPV- tumors from smokers. RESULTS: We observed more genes with variable messenger RNA expression in tumors compared with normal tissues, regardless of HPV and smoking status, and more microRNAs with variable expression in HPV- and HPV+ tumors from smoking patients than from nonsmokers. For both the messenger RNA and microRNA data, we observed more variance among HPV- tumors from smokers compared with HPV+ tumors from nonsmokers. The gene coexpression network construction highlighted pathways that have lost robustness in carcinogen-induced tumors but appear stable in virally induced tumors. CONCLUSIONS: Using coefficients of variation and coexpression networks, we identified multiple altered pathways that may play a role in carcinogen-driven tumorigenesis. PMID- 26132604 TI - Fatal Neuroleptic Malignant Syndrome Associated With Quetiapine. AB - Acute psychosis developed in an elderly patient with Parkinson disease and she was admitted and treated with quetiapine (Seroquel). One day later, high fever unexplained by infection appeared associated with restlessness, confusion, convulsion, leukocytosis, and extreme serum creatine kinase levels. She died of neuroleptic malignant syndrome (NMS) despite intensive treatment. Quetiapine is an atypical neuroleptic agent, rarely associated with NMS in the absence of other contributing drugs. Our case strongly establishes quetiapine-induced NMS (Naranjo scale 6) and is also unique in the abrupt onset and severe refractory course. The steep increase in the prescription of quetiapine worldwide mandates better recognition of this severe adverse reaction, which is fortunately rare, to allow immediate drug withdrawal and appropriate treatment. PMID- 26132606 TI - Introduction: Intracranial aneurysm surgery, part 2. PMID- 26132605 TI - Potential clinical application of interleukin-27 as an antitumor agent. AB - Cancer immunotherapies such as sipuleucel-T and ipilimumab are promising new treatments that harness the power of the immune system to fight cancer and achieve long-lasting remission. Interleukin (IL)-27, a member of the IL-12 heterodimeric cytokine family, has pleiotropic functions in the regulation of immune responses with both pro-inflammatory and anti-inflammatory properties. Evidence obtained using a variety of preclinical mouse models indicates that IL 27 possesses potent antitumor activity against various types of tumors through multiple mechanisms without apparent adverse effects. These mechanisms include those mediated not only by CD8(+) T cells, natural killer cells and macrophages, but also by antibody-dependent cell-mediated cytotoxicity, antiangiogenesis, direct antiproliferative effects, inhibition of expression of cyclooxygenase-2 and prostaglandin E2 , and suppression of epithelial-mesenchymal transition, depending on the characteristics of individual tumors. However, the endogenous role of IL-27 subunits and one of its receptor subunits, WSX-1, in the susceptibility to tumor development after transplantation of tumor cell lines or endogenously arising tumors seems to be more complicated. IL-27 functions as a double-edged sword: IL-27 increases IL-10 production and the expression of programmed death ligand 1 and T-cell immunoglobulin and mucin domain-3, and promotes the generation of regulatory T cells, and IL-27 receptor alpha singling enhances transformation; IL-27 may augment protumor effects as well. Here, we review both facets of IL-27, antitumor effects and protumor effects, and discuss the potential clinical application of IL-27 as an antitumor agent. PMID- 26132607 TI - Left pterional craniotomy for thrombectomy and clipping of ruptured left MCA giant aneurysm. AB - Giant aneurysms present a challenge to cerebrovascular surgeons on many fronts. These lesions have significant mass effect on surrounding tissues and are often partially thrombosed with thickened or calcified walls; these difficulties are amplified in cases of subarachnoid hemorrhage. The treatment of these lesions often requires debulking or resection of the aneurysm with or without trapping and bypassing the aneurysm segment. The case presented is of a man with a ruptured giant left middle cerebral artery (MCA) aneurysm presenting with seizure. The treatment of this giant aneurysm involves dissection, opening and internal evacuation including the use of ultrasonic aspiration, resection, and clipping. The patient was given aspirin preoperatively in preparation for possible superficial temporal artery-MCA or saphenous vein bypass if clipping was not possible. Vessel patency was evaluated using intraoperative Doppler and indocyanine green angiography. Intraoperative somatosensory and motor evoked potential monitoring is performed in all cases. Postoperatively, the patient was neurologically intact. At 1 year his modified Rankin Scale is 1, with his only symptom being intermittent headache. The video can be found here: http://youtu.be/8dimNdiIObE . PMID- 26132608 TI - Clipping of a ruptured anterior communicating artery aneurysm with right A1-A2 sectioning and reanastomosis. AB - We showcase the microsurgical clipping of a previously coiled and ruptured anterior communicating artery aneurysm, done through a right-sided approach. Initial clipping with a fenestrated clip occluded the flow in the right A2. After temporary clipping of both A1 and A2 vessels, we cut the right A1 and A2, clipped the aneurysm with a straight clip while preserving the flow in the left A1 and A2 and then performed reanastomosis of the right A1-A2 in an end to end fashion. This strategy allowed for complete obliteration of the aneurysm while preserving the flow in all four vessels. The video can be found here: http://youtu.be/4Y024zU5NVo. PMID- 26132609 TI - Microsurgical technique of symptomatic intracavernous aneurysm. AB - Symptomatic intracavernous aneurysm is rare. Cranial nerves in the cavernous sinus are subjected to the mass effect of an expanding aneurysm. Microsurgical clipping is the treatment of choice to relieve compressive cranial neuropathy. In this video, the authors present a case of intracavernous aneurysm causing diplopia, ptosis, and facial numbness. The patient was operated on via a pretemporal transclinoid-transcavernous approach. The aneurysm was completely obliterated through direct clipping. There were no new-onset neurologic deficits and complications after the operation. Complete recovery of the diplopia, ptosis, and facial numbness was observed at the 6-month postoperative follow up. The video can be found here: http://youtu.be/4w5QUoNIAQM. PMID- 26132610 TI - Microsurgical clip reconstruction techniques for aneurysms with significant calcified neck. AB - A common surgical complication of clipping aneurysms with a calcified neck is the calcified atheroma compromising the parent arteries after clipping the neck. Clips can slip downward at the calcified neck or cause calcified atheroma encroaching the parent arteries. This video demonstrates a reconstructive clip technique to avoid these issues. A fenes-trated clip is placed first to reconstruct the distal parent artery-aneurysm neck with the fenestrated ring over the thickest calcification. Then, a straight clip reconstructs the proximal artery-aneurysm junction, leaving the thickest point of calcified walls pinching together by themselves to achieve aneurysm occlusion while preserving the parent arteries. The video can be found here: http://youtu.be/9CM3o5_qlNQ. PMID- 26132611 TI - Microsurgical clipping of a giant vertebrobasilar junction aneurysm under hypothermic circulatory arrest. AB - Giant posterior circulation aneurysms pose a significant challenge to neurovascular surgeons. Among various treatment methods that have been applied individually or in combination, clipping under hypothermic circulatory arrest (HCA) is rarely used. We present a 62-year-old man who initially underwent coil occlusion of the right vertebral artery (VA) for a 2.5 cm giant vertebrobasilar junction (VBJ) aneurysm. His neurological condition had declined gradually and the aneurysm grew to 4 cm in size. The patient underwent clip reconstruction of giant VBJ aneurysm under HCA. His postoperative course was prolonged due to his preexisting neurological deficits. His preoperative Modified Rankin Score was 5, and improved postoperatively to 3 at three and six months, and to 2 at one year. The video can be found here: http://youtu.be/L53SiLV8eJY. PMID- 26132612 TI - ICA aneurysm surgically treated utilizing a choroidal to PCOM bypass and vein bypass. AB - This video shows the surgical repair of a 2.3 cm ICA aneurysm found in a 58-year old woman, who presented for right eye vision changes. The patient underwent a right modified orbitozygomatic craniotomy and saphenous vein bypass from the common carotid to the temporal M2. The aneurysm was then opened and repaired. However, since the anterior choroidal artery was not filling, a salvage bypass between the anterior choroidal and the PCOM was done. Both bypasses were patent and the patient has done well with a mRS of 1 for vision symptoms. The video can be found here: http://youtu.be/ciMyzfXgo8l. PMID- 26132613 TI - Clipping of posteriorly projecting large posterior communicating aneurysm via transsylvian anterior temporal approach. AB - Clipping of a posterior projecting large posterior communicating aneurysm via transsylvian anterior temporal approach is presented. To expose and clip this large aneurysm, retraction of the temporal lobe is required via the conventional pterional approach. In this video, we demonstrate microsurgical techniques as to how to dissect and mobilize the sylvian veins as well as a bridging vein to the sphenoparietal sinus, and the middle cerebral artery branches to the frontal lobe side. After the microsurgical dissection, a wide anteriolateral temporal space is obtained without significant temporal lobe retraction. The aneurysm was completely obliterated via this approach. The video can be found here: http://youtu.be/vU9Nxm7Yn-A. PMID- 26132614 TI - Microsurgical confirmation of perforating arteries arising from the fundus of a posterior communicating artery aneurysm. AB - Perforating arteries rarely project from the fundus of an aneurysm. We present the case of a 35-year-old woman who was found to have a right posterior communicating artery (PCOM) aneurysm via catheter angiography. Superselective microcatheter angiography revealed that perforating arteries arose from the aneurysm fundus that supplied the anterolateral thalamus. Microsurgical exploration confirmed several small perforating arteries arising from the aneurysm dome as well as an atretic distal PCOM artery. Given the complex anatomy, the lesion was unsuitable for clipping. We propose that this aneurysm represents a developmental variant whereby the proximal PCOM artery becomes atretic and terminates in PCOM perforators. The video can be found here: http://youtu.be/iDcp9fsDjq4. PMID- 26132615 TI - "Picket Fence" clipping technique for large and complex aneurysms. AB - The "picket fence" clipping technique is a method for clipping large aneurysms when conventional clipping across the neck is not feasible, either due to complex anatomy, atherosclerosis, calcification, or compromise of branch origins. This has also been described as a dome fenestration tube. Parallel straight clips, simple and/or fenestrated, are stacked vertically from dome to neck with the tips reconstructing the neck. In this video, the "picket fence" clipping technique is demonstrated on a large middle cerebral artery (MCA) aneurysm. A total of 14 clips reconstructed the neck, completely occluding the aneurysm and preserving outflow in all branch vessels. The video can be found here: http://youtu.be/0N5rYR6Op8Y. PMID- 26132616 TI - Microsurgical management of a large ICA bifurcation aneurysm. AB - A 70-year-old man with progressive visual disturbances, left superior quadrantanopsia, and right-sided papilledema underwent imaging that demonstrated a right internal carotid artery (ICA) terminus aneurysm with third-ventricle mass effect and ipsilateral optic nerve and chiasm compression. We performed a right modified orbitozygomatic craniotomy, with proximal control and dissection of the aneurysm and small perforator arteries. Temporary ICA and anterior cerebral artery (ACA) clips allowed placement of a large curved permanent clip, reconstructing the ICA bifurcation and maintaining adequate patency of the ACA and middle cerebral artery. Complete aneurysm obliteration was confirmed by intraoperative indocyanine green angiography and postoperative CT angiography. The video can be found here: http://youtu.be/5WEEgmA-g2A. PMID- 26132617 TI - Microsurgical treatment of recurrent coiled aneurysms. AB - The number of endovascularly-treated aneurysms has steadily increased over the past two decades. A small but significant number of recurrent or partially recanalized aneurysms have been identified. If repeat endovascular therapies are not feasible due to anatomical or technical considerations, surgical clipping may be considered. The technical challenges in the microsurgical treatment include coils interfering with the clip application; the possibility of an aneurysm that is less collapsible and less easy to manipulate; and intraluminal thrombus formation requiring thrombus and coil removal. The video presents the technical steps and nuances for clipping. The technical issues for coil removal are illustrated in two cases. The video can be found here: http://youtu.be/NvhSDVT4iuE. PMID- 26132618 TI - Technical nuances of clipping a middle cerebral artery bifurcation aneurysm. AB - Broad-necked middle cerebral artery aneurysms present unique challenges for the vascular neurosurgeon, who must contend with smaller vessels and often a complex clipping strategy. Due to their superficial location, these lesions are still commonly selected for microsurgical clipping. We present a case of a 42-year-old woman with significant vascular disease with a right middle cerebral artery aneurysm. We discuss the key surgical steps, demonstrate the microsurgical dissection and intraoperative rupture encountered and the final clipping strategy, as well as the postoperative course in this operative video presentation. The video can be found here: http://youtu.be/qZ2gvqz7XdQ . PMID- 26132619 TI - Intracranial blister aneurysms: clip reconstruction techniques. AB - Intracranial blister aneurysms are difficult to treat cerebrovascular lesions that typically affect the anterior circulation. These rare aneurysms can lead to acute rupture which usually cannot be treated via endovascular methods, but still require urgent surgical intervention. Surgical options are limited given their unique pathology and often require a combination of wrapping and clip reconstruction. In this video we present two patients with acute subarachnoid hemorrhage secondary to ruptured blister aneurysms. We demonstrate several surgical techniques for repairing the vascular defect with and without intraoperative rupture. The video can be found here: http://youtu.be/nz-JM45uKQU. PMID- 26132620 TI - Ophthalmic artery aneurysm treated by surgical clipping and balloon-assisted temporary carotid occlusion. AB - A 29-year-old woman is diagnosed with a large broad-base right ophthalmic artery aneurysm. Despite an intact visual field, she complained of mild right visual blurriness. Between endovascular and surgical treatments, surgery was favored due to her young age. It was decided to perform the surgery with simultaneous endovascular temporary carotid balloon occlusion. A right pterional craniotomy and intradural anterior clinoidectomy were performed, the balloon was positioned in the petrous carotid, and the distal durai ring was opened exposing the proximal neck. Under temporary proximal carotid balloon occlusion and distal carotid clip occlusion, the aneurysm was fully dissected and clipped. Intraoperative angiogram confirmed complete aneurysm occlusion and patency of the ophthalmic artery. The patient's neurological exam remained unchanged. The video can be found here: http://youtu.be/BIQKTl9bDqA . PMID- 26132621 TI - Direct suction decompression and fenestrated clip reconstruction of complex paraclinoid carotid artery aneurysm: operative video and nuances of skull base technique. AB - Direct microsurgical clipping of complex paraclinoid carotid artery aneuryms remains a formidable technical challenge due to the auneurysm's deep location at the skull base, with adjacent bony anatomy, large size, wide neck, and complex neuroanatomical relationships. In this operative video atlas manuscript, the author demonstrates a step-by-step technique for microsurgical clip reconstruction of a large complex ventral paraclinoid carotid artery aneurysm, using a trapping and direct suction decompression strategy followed by multiple fenestrated clip reconstruction of the internal carotid artery (ICA) via a modified orbitozygomatic approach. The nuances of skull base techniques are illustrated including extradural optic nerve decompression, extradural anterior clinoidectomy, incision of the falciform ligament to untether the optic nerve, and release of the distal durai ring to obtain proximal control. Reconstruction of the ICA and preservation of the anterior choroidal artery were achieved with multiple fenestrated clips. Aneurysm obliteration and patency of flow through the ICA was confirmed on video indocyanine green and catheter angiography. Although novel endovascular strategies continue to evolve, these microsurgical skull base techniques should remain in the surgical armamentarium for treating these complex cranial base vascular lesions. The video can be found here: http://youtu.be/IPS6lslk1ds. PMID- 26132622 TI - Clip reconstruction of giant vertebral artery aneurysm after failed flow reduction therapy. AB - Flow reduction therapy is sometimes utilized for difficult aneurysms, but it does not always work. A 42-year-old man presented with headache, dizziness, and slight gait disturbance due to left thrombosed giant vertebral aneurysm. Clip ligation of the VA after the PICA origin was performed for flow reduction based on the CFD analysis. Two months later, the aneurysm showed minor hemorrhage and hydrocephalus, and thrombectomy and clip reconstruction of the VA was performed. He returned to work with slight ipsilateral facial palsy (House & Brackmann grade 2). The video can be found here: http://youtu.be/-AUVk6nxefQ. PMID- 26132623 TI - Far-lateral transcondylar approach for microsurgical trapping of an anterior inferior cerebellar artery aneurysm. AB - Aneurysms of the posterior circulation remain challenging lesions given their proximity to the brainstem and cranial nerves. Many of these aneurysms may best be approached through a retrosigmoid-suboccipital craniectomy with a far-lateral transcondylar extension. In this narrated video illustration, we present the case of a 37-year-old man with an incidentally discovered right-sided anterior inferior cerebellar artery (AICA) aneurysm. Diagnostic studies included CT angiography and cerebral angiography. A suboccipital craniectomy and far-lateral transcondylar extension were performed for microsurgical trapping and excision of the AICA aneurysm. The techniques of the retrosigmoid craniectomy, C-1 laminectomy, condylectomy and microsurgical trapping of the aneurysm are reviewed. The video can be found here: http://youtu.be/JiM3CXVwXnk. PMID- 26132624 TI - Left temporal craniotomy for clipping of fusiform aneurysm of posterior cerebral artery. AB - Aneurysms of the posterior cerebral artery (PCA) are a distinct pathological entity and are surgically challenging. Fusiform aneurysms involving the PCA are quite rare and scarcely reported in the literature. In this video, we demonstrate the utility of the subtemporal approach to surgically reconstruct an unruptured, fusiform aneurysm of the left PCA, located at the junction of P3 and P4 segments. Curved clips were used to reconstruct the aneurysm such that flow was maintained in the parent vessel as well as distal branches. Postoperatively, the patient remained neurologically intact. The video can be found here: http://youtu.be/l7yzUPsaMc4. PMID- 26132625 TI - Cranio-orbito-zygomatic approach for a previously coiled/recurrent giant MCA aneurysm in a hybrid angio/OR suite. AB - We present surgical clipping of a giant middle cerebral artery aneurysm. The patient is a 64-year-old woman who suffered subarachnoid hemorrhage in 2005. She was treated with coiling of the aneurysm at an outside institution. She presented to our clinic with headaches and was found on angiography to have giant recurrence of the aneurysm. To allow adequate exposure for clipping, we performed the surgery through a cranio-orbito-zygomatic (COZ) skull base approach, which is demonstrated. The surgery was performed in an operating room/angiography hybrid suite allowing for high quality intraoperative angiography. The technique and room flow are also demonstrated. The video can be found here: http://youtu.be/eePcyOMi85M. PMID- 26132626 TI - Contralateral approach for clipping of bilateral anterior circulation aneurysms. AB - Patients with bilateral anterior circulation aneurysms present a management challenge. These lesions may be treated in a staged manner or alternatively, for select patients, a contralateral approach may be utilized to treat bilateral aneurysms with a single surgery. In this narrated video illustration, we present the case of a 57-year-old woman with incidentally discovered bilateral aneurysms (left middle cerebral artery [MCA], left anterior choroidal artery and right MCA). A contralateral approach through a left pterional craniotomy was performed formicrosurgical clipping of all three aneurysms. The techniques of pterional craniotomy, contralateral approach, microsurgical clipping and intraoperative angiography are reviewed. The authors are grateful to Wuyang Yang, M.D. for his assistance. The video can be found here: http://youtu.be/MlPIu3hQZkg. PMID- 26132627 TI - Conditional Deletion of TAK1 in T Cells Reveals a Pivotal Role of TCRalphabeta+ Intraepithelial Lymphocytes in Preventing Lymphopenia-Associated Colitis. AB - The kinase TAK is required for the development of conventional and regulatory T cells. We previously reported that mice with conditional deletion of TAK1 in T cells (Lck-cre:TAK1fl/fl mice) exhibited severe T lymphopenia, and were nevertheless predisposed to spontaneous colitis with unknown etiology. Here we focused on the immunopathological mechanism in colitic Lck-cre:TAK1fl/fl mice. We found that 'leaky' CD4+ T cells retaining TAK1 acquired inflammatory phenotypes that contribute to disease onset in Lck-cre:TAK1fl/fl mice. Furthermore, the gut microbiota-triggered signaling was also a key event leading to the pathogenesis. We discovered that Lck-cre:TAK1fl/fl mice were almost completely devoid of TCRalphabeta+CD8alpha+ intestinal intraepithelial lymphocytes (IELs) and this was largely due to the developmental defect of the thymic precursors by TAK1 deficiency. Remarkably, transfer of TCRalphabeta+CD8alpha+ IELs from wild-type mice ameliorated colitis in Lck-cre:TAK1fl/fl mice. Taken together, our current study highlighted the emerging role of TAK1 in configuring the gut-specialized T cell subset, which regulates mucosal homeostasis under lymphopenic conditions. PMID- 26132629 TI - Office management of obstructive sleep apnoea: appliances. AB - PURPOSE OF REVIEW: Oral appliances are becoming increasingly common in the treatment of obstructive sleep apnoea (OSA). They work by advancing the mandible and opening the pharynx. There are several types of devices available for use. Many patients intolerant to continuous positive airway pressure (CPAP) are using oral appliances for OSA. RECENT FINDINGS: Oral appliances have been shown to improve polysomnography, quality of life and health measures associated with OSA. There is current work to better identify patients who are ideal candidates. Development of titratable devices and monitoring are optimizing usage. They have been compared with CPAP, with both showing improvement in OSA; however, CPAP remains superior overall. SUMMARY: Oral appliances are becoming first-line therapy for mild and moderate OSA. They provide a meaningful alternative in severe OSA for patients unable to use CPAP. Device titration and usage monitoring are beginning to hone oral appliances as a therapeutic option. PMID- 26132628 TI - Generation of Recombinant Human IgG Monoclonal Antibodies from Immortalized Sorted B Cells. AB - Finding new methods for generating human monoclonal antibodies is an active research field that is important for both basic and applied sciences, including the development of immunotherapeutics. However, the techniques to identify and produce such antibodies tend to be arduous and sometimes the heavy and light chain pair of the antibodies are dissociated. Here, we describe a relatively simple, straightforward protocol to produce human recombinant monoclonal antibodies from human peripheral blood mononuclear cells using immortalization with Epstein-Barr Virus (EBV) and Toll-like receptor 9 activation. With an adequate staining, B cells producing antibodies can be isolated for subsequent immortalization and clonal expansion. The antibody transcripts produced by the immortalized B cell clones can be amplified by PCR, sequenced as corresponding heavy and light chain pairs and cloned into immunoglobulin expression vectors. The antibodies obtained with this technique can be powerful tools to study relevant human immune responses, including autoimmunity, and create the basis for new therapeutics. PMID- 26132630 TI - Update on the evidence for functional rhinoplasty techniques. AB - PURPOSE OF REVIEW: Functional rhinoplasty is a term that is commonly used to describe any technique used to address nasal obstruction in the nasal valve region. The cause of nasal valve collapse differs based on the site. Internal valve collapse may be idiopathic or associated with previous rhinoplasty, trauma, or weakened cartilage in older patients. External valve collapse is usually idiopathic and less likely to be associated with previous surgery. Various techniques have been developed over time, and the data in support of functional rhinoplasty continue to increase. RECENT FINDINGS: This article discusses popular techniques currently in use, as well as newer techniques that have been described over the past several years. In addition, there is a trend toward utilizing objective testing and validated assessment scales to assess postoperative changes. SUMMARY: Functional rhinoplasty utilizes a multitude of techniques to address nasal valve collapse. Although high-level data are lacking, the current literature is in support of nasal valve correction to improve nasal breathing. Most importantly, the technique employed is unique for each patient. PMID- 26132632 TI - Effects of Concentration on Like-Charge Pairing of Guanidinium Ions and on the Structure of Water: An All-Atom Molecular Dynamics Simulation Study. AB - Like-charge ion-pair formation in an aqueous solution of guanidinium chloride (GdmCl) has two important facets. On one hand, it describes the role of the arginine (ARG) side chain in aggregation and dimer formation in proteins, and on the other hand, it lends support for the direct mechanism of protein denaturation by GdmCl. We employ all-atom molecular dynamics simulations to investigate the effect of GdmCl concentration on the like-charge ion-pair formation of guanidinium ions (Gdm(+)). From analyses of the radial distribution function (RDF) between the carbon atoms of two guanidinium moieties, the existence of both contact pairs and solvent-separated pairs has been observed. Although the peak height corresponding to the contact-pair state decreases, the number of Gdm(+) ions in the contact-pair state actually increases with increasing GdmCl concentration. We have also investigated the effect of the concentration of Gdm(+) on the structure of water. The effect of GdmCl concentration on the radial and tetrahedral structures of water is found to be negligibly small; however, GdmCl concentration has a considerable effect on the hydrogen-bonding structure of water. It is demonstrated that the presence of chloride ions, not Gdm(+), in the first solvation shell of water causes the distortion in the hydrogen-bonding network of water. In order to establish that Gdm(+) not only stacks against another Gdm(+) but also directly attacks the ARG residue of a protein or peptide, simulation of an ARG-rich peptide in 6 M aqueous solution of GdmCl has been performed. The analyses of RDFs and orientation distributions reveal that the Gdm(+) moiety of the GdmCl attacks the same moiety in the ARG side chain with a parallel stacking orientation. PMID- 26132631 TI - An Injectable and Drug-loaded Supramolecular Hydrogel for Local Catheter Injection into the Pig Heart. AB - Regeneration of lost myocardium is an important goal for future therapies because of the increasing occurrence of chronic ischemic heart failure and the limited access to donor hearts. An example of a treatment to recover the function of the heart consists of the local delivery of drugs and bioactives from a hydrogel. In this paper a method is introduced to formulate and inject a drug-loaded hydrogel non-invasively and side-specific into the pig heart using a long, flexible catheter. The use of 3-D electromechanical mapping and injection via a catheter allows side-specific treatment of the myocardium. To provide a hydrogel compatible with this catheter, a supramolecular hydrogel is used because of the convenient switching from a gel to a solution state using environmental triggers. At basic pH this ureido-pyrimidinone modified poly(ethylene glycol) acts as a Newtonian fluid which can be easily injected, but at physiological pH the solution rapidly switches into a gel. These mild switching conditions allow for the incorporation of bioactive drugs and bioactive species, such as growth factors and exosomes as we present here in both in vitro and in vivo experiments. The in vitro experiments give an on forehand indication of the gel stability and drug release, which allows for tuning of the gel and release properties before the subsequent application in vivo. This combination allows for the optimal tuning of the gel to the used bioactive compounds and species, and the injection system. PMID- 26132633 TI - Effect of (minor or major) maternal trauma on fetal motility: A prospective study. AB - BACKGROUND: Fetal motility represents the spontaneous activity of the central nervous system and as such can be used to evaluate its functional integrity. Maternal mechanical trauma in pregnancy is a risk factor for hypoxic ischemic brain injury and can potentially affect the CNS and fetal motility. AIM: To study motility in fetuses after maternal trauma. STUDY DESIGN: Prospective study; 1-h sonographic observations at 2-8h (T1), 24-72h (T2) and >72h (T3) after trauma. SUBJECTS: Fetuses exposed to trauma after 20weeks gestational age. OUTCOME MEASURES: Motor aspects; differentiation into specific movement patterns, quality and quantity of general movements were compared to a normal population. Obstetrical outcome; neurological outcome at term and 1year of age. RESULTS: Sixteen fetuses were examined between 2012 and 2014. Median gestational age at time of trauma was 25+6 (range 20-38) weeks. Most traumas were traffic accidents or falls, injuries were mainly minor. Motility assessment showed abnormal differentiation in 2/16; 2/14 and 0/16; abnormal quality in 2/16; 3/14 and 6/16; and abnormal quantity in 6/16, 9/14 and 9/16 at T1, T2 and T3 respectively. Preterm delivery occurred once. Neurological development was normal in 13/14 infants at term and 14/14 at one year. CONCLUSIONS: This study shows that maternal trauma affected fetal motility in the majority of the fetuses. The changes in motility support the concern that even minor mechanical trauma may have influence on the functional integrity of the central nervous system, although no neurological sequelae were present at 1year. PMID- 26132634 TI - Development of an impurity-profiling method for source identification of spilled benzene series compounds by gas chromatography with mass spectrometry: Toluene as a case study. AB - In this study, an impurity profiling method was established for the source identification of spilled benzene series compounds. Toluene was used as a case study to demonstrate the feasibility of this approach. Gas chromatography with mass spectrometry was applied for identification and quantification of the impurities including ethyl benzene, p-xylene, m-xylene, and o-xylene in toluene. Impurities in toluene were detected at very low levels by applying mass spectrometry in selected-ion monitoring mode. Eight authentic toluene samples collected from different manufacturers were analyzed by the developed gas chromatography with mass spectrometry method to construct the characteristic impurity profiling of toluene. Then, combined with scatter distribution, similarity analysis and t-test, a suite of diagnostic ratios based on the impurity distribution was used for the differentiation of toluene from different sources. Results indicated that scatter distribution method can discriminate the original toluene samples from different manufacturers. Similarity calculation and t-test methods can identify effectively the weathered toluene samples. The proposed impurity profiling method was useful for discrimination between toluene samples from different sources. Statistical analysis of these impurity profiles demonstrated the potential to investigate whether two questioned spilled toluene samples encountered in forensic casework are from the same source. PMID- 26132636 TI - Glycated Reconstructed Human Skin as a Platform to Study the Pathogenesis of Skin Aging. AB - The advanced glycation end products (AGEs) of proteins are common factors in the pathophysiology of a number of disorders related to aging. The skin generation of AGEs occurs mainly through nonenzymatic glycation reactions of extracellular matrix (ECM) proteins in the dermis. The AGEs have been touted as one of the factors responsible for healing impairment and loss of elasticity of healing skin, affecting growth, differentiation, and cellular motility, as well as cytokines response, metalloproteinases expression, and vascular hemostasis. In this study, we generated an in vitro full-thickness reconstructed skin based on a glycated collagen matrix dermal compartment to evaluate the effects of glycation on dermal ECM and ultimately on the epidermis. Epidermal differentiation and stratification patterns and the glycation-induced ECM changes were evaluated by histology, immunohistochemistry, and mRNA levels. In this study, we reported for the first time that changes in the dermal matrix caused by collagen I in vitro glycation processes also affect the epidermal compartment. We demonstrated that glycation of collagen induces expression of carboxymethyllysine in dermal and epidermal compartments and, consequently, an aging phenotype consisting of poor stratification of epidermal layers and vacuolization of keratinocyte cytoplasm. Increased expression of cell-cell adhesion markers, such as desmoglein and E cadherin in glycated skins, is observed in the stratum spinosum, as well as an increased compression of dermal collagen matrix. We also submitted our 3D model of reconstructed glycated skin to screening of anti-AGE molecules, such as aminoguanidine, which prevented the glycated morphological status. Controlled human studies investigating the effects of anti-AGE strategies against skin aging are largely missing. In this context, we proposed the use of skin equivalents as an efficient model to investigate cellular interactions and ECM changes in the aging skin, and to elucidate the role of anti-AGEs molecules in this process. PMID- 26132635 TI - Occurrence and Characterization of Cronobacter spp. in Dehydrated Rice Powder from Chinese Supermarket. AB - Cronobacter spp. are emerging food-borne pathogens and have been identified as causative agents of meningitis and necrotizing enterocolitis in infants. Dehydrated rice is popular with a wide range of people and it is frequently used as a substitute for infant milk powder to baby older than four months. The occurrence of Cronobacter spp. was investigated in 1,012 samples of dehydrated rice powder collected from 14 manufacturers in China during 2010 to 2012. The isolates were identified using fusA allele sequencing and subtyped using pulsed field gel electrophoresis. Seventy-six samples (7.5%) contained Cronobacter spp. The prevalence among manufacturers ranged from 0-28.8%. The 76 isolates included 4 species [Cronobacter sakazakii (52 isolates) Cronobacter malonaticus (14 isolates), Cronobacter dublinensis (7 isolates), and Cronobacter muytjensii (3 isolates)]. Twenty-three unique fusA alleles and sixty-six PFGE-patterns were detected. All isolated strains were observed to be sensitive or to show intermediate susceptibility to eight tested antimicrobial agents. The study revealed serious contamination of dehydrated rice powder by Cronobacter spp., with prevalence varying among manufacturers in China. Identified Cronobacter species, fusA alleles, and subtypes were diverse. PMID- 26132637 TI - Quantitative Analysis of Climbing Defects in a Drosophila Model of Neurodegenerative Disorders. AB - Locomotive defects resulting from neurodegenerative disorders can be a late onset symptom of disease, following years of subclinical degeneration, and thus current therapeutic treatment strategies are not curative. Through the use of whole exome sequencing, an increasing number of genes have been identified to play a role in human locomotion. Despite identifying these genes, it is not known how these genes are crucial to normal locomotive functioning. Therefore, a reliable assay, which utilizes model organisms to elucidate the role of these genes in order to identify novel targets of therapeutic interest, is needed more than ever. We have designed a sensitized version of the negative geotaxis assay that allows for the detection of milder defects earlier and has the ability to evaluate these defects over time. The assay is performed in a glass graduated cylinder, which is sealed with a wax barrier film. By increasing the threshold distance to be climbed to 17.5 cm and increasing the experiment duration to 2 min we have observed a greater sensitivity in detecting mild mobility dysfunctions. The assay is cost effective and does not require extensive training to obtain highly reproducible results. This makes it an excellent technique for screening candidate drugs in Drosophila mutants with locomotion defects. PMID- 26132638 TI - Multicenter Analysis of the Factors Associated With Unplanned Extubation in the PICU. AB - OBJECTIVE: To identify factors associated with unplanned extubation in PICUs. DESIGN: A prospective, case-controlled multicenter study. SETTING: Eleven Pediatric Intensive Care Units collaborating through the National Association of Children's Hospitals and Related Institutions PICU focus group. PATIENTS: Patients with unplanned extubation events and control patients without unplanned extubation. INTERVENTIONS: Unplanned extubation events were prospectively tracked for 1 year at 11 centers. When an unplanned extubation occurred, up to four controls were randomly identified of other intubated patients in the unit. For each event and control, data associated with unplanned extubation events, reintubation, and outcomes were collected. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-nine unplanned extubation events occurred out of 25,500 endotracheal tube days in the study (0.74 unplanned extubations/100 endotracheal days; 95% CI, 0.64-0.85), with 654 associated controls. Unplanned extubation rates ranged by site from 0.3 to 2.1 unplanned extubations/100 endotracheal days. Children less than 6 years had an increased rate of unplanned extubation (0.83 for < 6 yr vs 0.45 for >= 6 yr; p = 0.001). After multivariate analysis, inadequate patient sedation (odds ratio, 9.1; 95% CI, 4.5-18.5), loose or slimy endotracheal tube (odds ratio, 10.4; 95% CI, 5.0-22.2), a planned extubation in the next 12 hours (odds ratio, 2.3; 95% CI, 1.3-4.1), and a nurse pulled from another unit (odds ratio, 3.8; 95% CI, 1.4-9.9) were associated with unplanned extubation. Sixty percent of unplanned extubations required reintubation. CONCLUSIONS: The rate of unplanned extubation is higher in patients aged less than 6 years. Patient factors, such as decreased level of sedation, loose or slimy endotracheal tube, and staffing factors such as floating nurse from another unit, contribute to unplanned extubation in children. PMID- 26132640 TI - Quantitative O-Glycomics by Microwave-Assisted beta-Elimination in the Presence of Pyrazolone Analogues. AB - O-Linked glycosylation of serine/threonine residues is a posttranslational modification of proteins and is essential for protein recognition and lipid functions on cell surfaces and within cells. The characterization of differently structured O-linked glycans (O-glycans) is particularly challenging because there is no known endoglycosidase for such groups. Therefore, chemical digestion approaches have been widely used; however, it is sometimes difficult to suppress unwanted side reactions. Recently, we reported a novel O-glycomics procedure using beta-elimination in the presence of pyrazolone analogues (BEP). In the present study, we describe a microwave (MW)-assisted BEP procedure for rapid and quantitative O-glycomic analysis. Following optimization of the reaction conditions, the MW-assisted BEP reaction substantially improved the recovery of total O-glycans from model glycoproteins (PSM) and the reaction time was reduced from 16 to 2 h. Combined with sequential solid-phase extractions, this MW assisted BEP procedure enabled O-glycomic analyses of various biological samples. PMID- 26132639 TI - Chromosome Scaffold is a Double-Stranded Assembly of Scaffold Proteins. AB - Chromosome higher order structure has been an enigma for over a century. The most important structural finding has been the presence of a chromosome scaffold composed of non-histone proteins; so-called scaffold proteins. However, the organization and function of the scaffold are still controversial. Here, we use three dimensional-structured illumination microscopy (3D-SIM) and focused ion beam/scanning electron microscopy (FIB/SEM) to reveal the axial distributions of scaffold proteins in metaphase chromosomes comprising two strands. We also find that scaffold protein can adaptably recover its original localization after chromosome reversion in the presence of cations. This reversion to the original morphology underscores the role of the scaffold for intrinsic structural integrity of chromosomes. We therefore propose a new structural model of the chromosome scaffold that includes twisted double strands, consistent with the physical properties of chromosomal bending flexibility and rigidity. Our model provides new insights into chromosome higher order structure. PMID- 26132641 TI - Single-Step Synthesis of 5,6,7,8-Tetrahydroindolizines via Annulation of 2 Formylpiperidine and 1,3-Dicarbonyl Compounds. AB - An expedient single-step synthesis of 5,6,7,8-tetrahydroindolizines has been achieved via the annulation of commercially available 2-formylpiperidine hydrochloride and 1,3-dicarbonyl compounds in THF in the presence of pyrrolidine and 4 A molecular sieves. A variety of beta-ketoesters, ketones, and amides participated in this annulation chemistry, affording the desired 5,6,7,8 tetrahydroindolizines in moderate to good yields. PMID- 26132642 TI - Ergogenic Effects of Caffeine Consumption in a 3-min All-Out Arm Crank Test in Paraplegic and Tetraplegic Compared With Able-Bodied Individuals. AB - The aim of our study was to investigate the effect of caffeine supplementation on 3-min all-out arm crank exercise performance in paraplegic (P) and tetraplegic (T) compared with able-bodied (AB) participants. A placebo-controlled, randomized, crossover, and double-blind study design was chosen to investigate the differences between caffeine (CAF) and placebo (PLC). In total, 34 healthy, trained participants were tested. Seventeen were AB (median [minimum; maximum] VO2peak: 33.9 mL/min/kg [23.6; 57.6]), 10 were P (VO2peak: 34.4 mL/min/kg [19.5; 48.8]), and 7 were T (VO2peak: 13.6 mL/min/kg [8.6; 16.3]). All participants performed two 3-min all-out tests on an arm crank ergometer following the ingestion of either PLC or CAF. Power output parameters, plasma caffeine (PC), epinephrine (EPI), and norepinephrine (NOR) concentrations were assessed. CAF significantly increased average power over the first 30 s (p = .028) and 60 s (p = .005) in P, but not in T (p = .61; p = .87) nor in AB (p = .25; p = .44). Peak power was increased in the CAF trial in AB (+46 W) as well as in P (+21 W) but was not significantly different from PLC (AB: p = .10; P: p = .17). PC significantly increased in all groups (AB: p = .002; P: p = .005; T: p = .018) whereas EPI showed a significant increase only in AB (p = .002) and in P (p = .018). NOR increased significantly in AB (p = .018) but did not increase in the other groups. Caffeine seems to enhance short-duration exercise performance in P. In contrast, T showed a high interindividual variability and overall no ergogenic effect was detected in this group. PMID- 26132651 TI - Standardless multicomponent qNMR analysis of compounds with overlapped resonances based on the combination of ICA and PULCON. AB - A fast and reliable nuclear magnetic resonance (NMR) method for quantitative analysis of targeted compounds with overlapped signals in complex mixtures has been established. The method is based on the combination of chemometric treatment for spectra deconvolution and the PULCON principle (pulse length based concentration determination) for quantification. Independent component analysis (ICA) (mutual information least dependent component analysis (MILCA) algorithm) was applied for spectra deconvolution in up to six component mixtures with known composition. The resolved matrices (independent components, ICs and ICA scores) were used for identification of analytes, calculating their relative concentrations and absolute integral intensity of selected resonances. The absolute analyte concentrations in multicomponent mixtures and authentic samples were then calculated using the PULCON principle. Instead of conventional application of absolute integral intensity in case of undisturbed signals, the multiplication of resolved IC absolute integral and its relative concentration in the mixture for each component was used. Correction factors that are required for quantification and are unique for each analyte were also estimated. The proposed method was applied for analysis of up to five components in lemon and orange juice samples with recoveries between 90% and 111%. The total duration of analysis is approximately 45 min including measurements, spectra decomposition and quantification. The results demonstrated that the proposed method is a promising tool for rapid simultaneous quantification of up to six components in case of spectral overlap and the absence of reference materials. PMID- 26132652 TI - Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling. AB - The mechanism of enzymatic peptide hydrolysis in matrix metalloproteinase-2 (MMP 2) was studied at atomic resolution through quantum mechanics/molecular mechanics (QM/MM) simulations. An all-atom three-dimensional molecular model was constructed on the basis of a crystal structure from the Protein Data Bank (ID: 1QIB), and the oligopeptide Ace-Gln-Gly~Ile-Ala-Gly-Nme was considered as the substrate. Two QM/MM software packages and several computational protocols were employed to calculate QM/MM energy profiles for a four-step mechanism involving an initial nucleophilic attack followed by hydrogen bond rearrangement, proton transfer, and C-N bond cleavage. These QM/MM calculations consistently yield rather low overall barriers for the chemical steps, in the range of 5-10 kcal/mol, for diverse QM treatments (PBE0, B3LYP, and BB1K density functionals as well as local coupled cluster treatments) and two MM force fields (CHARMM and AMBER). It, thus, seems likely that product release is the rate-limiting step in MMP-2 catalysis. This is supported by an exploration of various release channels through QM/MM reaction path calculations and steered molecular dynamics simulations. PMID- 26132653 TI - Metal-on-Metal Hip Arthroplasty: A Review of Adverse Reactions and Patient Management. AB - Recent alarming joint registry data highlighting increased revision rates has prompted further research into the area of metal-on-metal hip replacements and resurfacings. This review article examines the latest literature on the topic of adverse reactions to metal debris and summarises the most up-to-date guidelines on patient management. Adverse reactions to metal debris can cause significant damage to soft tissue and bone if not diagnosed early. Furthermore, not every patient with an adverse reaction to metal debris will be symptomatic. As such, clinicians must remain vigilant when assessing and investigating these patients in order to detect failing implants and initiate appropriate management. PMID- 26132654 TI - Postpartum Maternal and Neonatal Hospitalizations Among Women with HIV: A Population-Based Study. AB - Postpartum maternal and neonatal readmissions in the period shortly following birth are indicators of serious morbidity. We compared the risk of postpartum maternal and neonatal hospitalizations in women living with and without HIV in Ontario, Canada. We conducted a population-based study of pregnancies in Ontario between April 1, 2002 and March 31, 2011 using Ontario's administrative health care databases. Generalized estimating equations were used to derive adjusted odds ratios (aORs) and 95% confidence intervals (CI) for the association of HIV infection with postpartum maternal hospitalizations within 30 days of hospital discharge and neonatal hospitalizations within 30 and 60 days of hospital discharge. Between 2002/2003 and 2010/2011, 1,133,505 pregnancies were available for analysis, of which 634 (0.06%) were to women living with HIV. The proportion of postpartum maternal hospitalizations (2.8% versus 1.1%; odds ratio 2.53; 95% CI 1.57 to 4.07) was higher among women with HIV. The multivariable adjusted odds ratio was 1.54 (95% CI 0.93 to 2.55). The proportions of neonates hospitalized within 30 (2.6% versus 3.7%; aOR 0.68, 95% CI 0.42 to 1.10) and 60 days (4.9% versus 4.9%; aOR 0.86, 95% CI 0.60 to 1.24) of discharge were similar among infants born to women with and without HIV. Women living with HIV are at a higher risk of postpartum maternal hospitalizations than women not living with HIV. The effect of HIV infection was attenuated by multivariable adjustment, suggesting that sociodemographic or health care factors are responsible for much of the difference in outcomes. PMID- 26132655 TI - Viremia during pregnancy and risk of childhood leukemia and lymphomas in the offspring: Nested case-control study. AB - A possible role for infections of the pregnant mother in the development of childhood acute leukemias and lymphomas has been suggested. However, no specific infectious agent has been identified. Offspring of 74,000 mothers who had serum samples taken during pregnancy and stored in a large-scale biobank were followed up to the age of 15 years (750,000 person years) through over-generation linkages between the biobank files, the Swedish national population and cancer registers to identify incident leukemia/lymphoma cases in the offspring. First-trimester sera from mothers of 47 cases and 47 matched controls were retrieved and analyzed using next generation sequencing. Anelloviruses were the most common viruses detected, found in 37/47 cases and in 40/47 controls, respectively (OR: 0.6, 95% CI: 0.2-1.9). None of the detected viruses was associated with leukemia/lymphoma in the offspring. Viremia during pregnancy was common, but no association with leukemia/lymphoma risk in the offspring was found. PMID- 26132656 TI - Comparative Magnetic Resonance Imaging and Histopathological Correlates in Two SOD1 Transgenic Mouse Models of Amyotrophic Lateral Sclerosis. AB - Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal disease due to motoneuron degeneration. Magnetic resonance imaging (MRI) is becoming a promising non-invasive approach to monitor the disease course but a direct correlation with neuropathology is not feasible in human. Therefore in this study we aimed to examine MRI changes in relation to histopathology in two mouse models of ALS (C57BL6/J and 129S2/SvHsd SOD1G93A mice) with different disease onset and progression. A longitudinal in vivo analysis of T2 maps, compared to ex vivo histological changes, was performed on cranial motor nuclei. An increased T2 value was associated with a significant tissue vacuolization that occurred prior to motoneuron loss in the cranial nuclei of C57 SOD1G93A mice. Conversely, in 129Sv SOD1G93A mice, which exhibit a more severe phenotype, MRI detected a milder increase of T2 value, associated with a milder vacuolization. This suggests that alteration within brainstem nuclei is not predictive of a more severe phenotype in the SOD1G93A mouse model. Using an ex vivo paradigm, Diffusion Tensor Imaging was also applied to study white matter spinal cord degeneration. In contrast to degeneration of cranial nuclei, alterations in white matter and axons loss reflected the different disease phenotype of SOD1G93A mice. The correspondence between MRI and histology further highlights the potential of MRI to monitor progressive motoneuron and axonal degeneration non-invasively in vivo. The identification of prognostic markers of the disease nevertheless requires validation in multiple models of ALS to ensure that these are not merely model specific. Eventually this approach has the potential to lead to the development of robust and validated non-invasive imaging biomarkers in ALS patients, which may help to monitor the efficacy of therapies. PMID- 26132657 TI - Vestiges of an Ancient Border in the Contemporary Genetic Diversity of North Eastern Europe. AB - It has previously been demonstrated that the advance of the Neolithic Revolution from the Near East through Europe was decelerated in the northernmost confines of the continent, possibly as a result of space and resource competition with lingering Mesolithic populations. Finland was among the last domains to adopt a farming lifestyle, and is characterized by substructuring in the form of a distinct genetic border dividing the northeastern and southwestern regions of the country. To explore the origins of this divergence, the geographical patterns of mitochondrial and Y-chromosomal haplogroups of Neolithic and Mesolithic ancestry were assessed in Finnish populations. The distribution of these uniparental markers revealed a northeastern bias for hunter-gatherer haplogroups, while haplogroups associated with the farming lifestyle clustered in the southwest. In addition, a correlation could be observed between more ancient mitochondrial haplogroup age and eastern concentration. These results coupled with prior archeological evidence suggest the genetic northeast/southwest division observed in contemporary Finland represents an ancient vestigial border between Mesolithic and Neolithic populations undetectable in most other regions of Europe. PMID- 26132658 TI - The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease. AB - A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P <0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC >43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P <0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation. PMID- 26132659 TI - Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer. AB - Gliomas are a highly heterogeneous group of brain tumours that are refractory to treatment, highly invasive and pro-angiogenic. Glioblastoma patients have an average survival time of less than 15 months. Understanding the molecular basis of different grades of glioma, from well differentiated, low-grade tumours to high-grade tumours, is a key step in defining new therapeutic targets. Here we use a data-driven approach to learn the structure of gene regulatory networks from observational data and use the resulting models to formulate hypothesis on the molecular determinants of glioma stage. Remarkably, integration of available knowledge with functional genomics datasets representing clinical and pre clinical studies reveals important properties within the regulatory circuits controlling low and high-grade glioma. Our analyses first show that low and high grade gliomas are characterised by a switch in activity of two subsets of Rho GTPases. The first one is involved in maintaining normal glial cell function, while the second is linked to the establishment of multiple hallmarks of cancer. Next, the development and application of a novel data integration methodology reveals novel functions of RND3 in controlling glioma cell migration, invasion, proliferation, angiogenesis and clinical outcome. PMID- 26132671 TI - Nocebo effects in the treatment of major depression: results from an individual study participant-level meta-analysis of the placebo arm of duloxetine clinical trials. AB - BACKGROUND: The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. METHOD: This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. RESULTS: TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. DISCUSSION: In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. CONCLUSIONS: The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation. PMID- 26132670 TI - Positive psychiatry: its time has come. AB - Traditionally, psychiatry has been defined and practiced as a branch of medicine focused on the diagnosis and treatment of mental illnesses. Based on growing empirical evidence, we believe that this definition warrants expansion to include the concept of positive psychiatry. In the present article, we provide a critical overview of this emerging field and a select review of relevant scientific literature. Positive psychiatry may be defined as the science and practice of psychiatry that seeks to understand and promote well-being through assessment and interventions involving positive psychosocial characteristics (PPCs) in people who suffer from or are at high risk of developing mental or physical illnesses. It can also benefit nonclinical populations. Positive psychiatry has 4 main components: (1) positive mental health outcomes (eg, well-being), (2) PPCs that comprise psychological traits (resilience, optimism, personal mastery and coping self-efficacy, social engagement, spirituality and religiosity, and wisdom including compassion) and environmental factors (family dynamics, social support, and other environmental determinants of overall health), (3) biology of positive psychiatry constructs, and (4) positive psychiatry interventions including preventive ones. There are promising empirical data to suggest that positive traits may be improved through psychosocial and biological interventions. As a branch of medicine rooted in biology, psychiatry, especially with the proposed conceptualization of positive psychiatry, is well poised to provide major contributions to the positive mental health movement, thereby impacting the overall health care of the population. PMID- 26132672 TI - A 4-year follow-up of attention-deficit/hyperactivity disorder in a population sample. AB - BACKGROUND: Prior follow-up studies of attention-deficit/hyperactivity disorder (ADHD) ascertained ADHD cases in clinical samples mostly from North America but rarely from European countries. They have provided a good deal of information about the persistence of ADHD and its impairments, but the degree to which these results generalize to population samples and to other countries is not certain. Prior studies have also not assessed predictors of new-onset ADHD in youth without ADHD. METHOD: At baseline, 7,912 of 18 million telephone numbers were randomly selected from throughout France from October 2, 2008, through December 11, 2008. Among 4,186 eligible families, 1,012 (24.2%) were successfully recruited at baseline, when a telephone interview was administered to all families about a child in the 6- to 12-year age range. Four years later, we attempted to recruit the entire sample to assess the persistence of ADHD and its impairments and the emergence of new associated conditions. RESULTS: 86.5% of the families assessed at baseline were followed-up (N = 875). Participants who were and were not interviewed at follow-up did not differ on any clinical or demographic features. At follow-up, the prevalence of full or subthreshold ADHD was 65.8% for ADHD participants and 9.8% for those not having ADHD at baseline. Among the children who were not diagnosed with ADHD at baseline, 3.4% were diagnosed with ADHD at follow-up. Both the persistence of ADHD and new onsets of ADHD were significantly predicted by several baseline clinical features and by having a family history of ADHD (all P values < .05). CONCLUSIONS: We replicated prior predictors of ADHD's persistence and provide new data about predictors of new ADHD onsets in the population. Our data about subthreshold ADHD support a dimensional conceptualization of the disorder and address the potential clinical utility of a subthreshold diagnostic category. PMID- 26132673 TI - Choosing medications for treatment-resistant depression based on mechanism of action. PMID- 26132674 TI - Improving the practice of clinical psychopharmacotherapy: the process of long term management for patients and caregivers. PMID- 26132675 TI - Single-dose ketamine followed by daily D-Cycloserine in treatment-resistant bipolar depression. PMID- 26132676 TI - Maintaining the initial clinical response after ketamine in bipolar and unipolar depression: an important next-step challenge. PMID- 26132680 TI - Bioequivalence of generic drugs: a simple explanation for a US Food and Drug Administration requirement. AB - There is a widespread misconception that for a generic drug to be deemed bioequivalent to a branded drug, it must contain 80%-125% of the active ingredient that is present in the branded version. More correctly, bioequivalence is studied in randomized crossover trials that compare the generic drug with the reference agent, and the relevant outcome measures are pharmacokinetic (PK) parameters such as peak drug concentration and area under the curve, which describe the rate and extent of absorption of the drug. The ratio of each PK characteristic of the generic drug to the reference drug is computed; the ideal value of this ratio is 1:1, or just 1.00 (indicating a perfect match, or perfect bioequivalence). Because this ideal is probably unattainable, the US Food and Drug Administration requires that the 90% confidence interval of the PK ratio should lie between 0.80 and 1.25. For the entire 90% confidence interval to meet this requirement, the mean PK value of the generic product should actually lie quite close to that of the reference standard. Therefore, the variation between the generic and the reference is actually small. These concepts are explained in this article with the help of simple, easy-to-understand examples. PMID- 26132681 TI - Sex-specific association between antidepressant use and body weight in a population-based study in older adults. AB - OBJECTIVE: To investigate the association between antidepressant use and body weight in a population-based study in older adults. METHOD: All participant records (N = 7,269) from the prospective Rotterdam Study with data on anthropometrics and current depressive symptoms were studied post hoc (data were collected between September 1993 and December 2011). The association between antidepressant use, derived from pharmacy records, and change in body mass index (BMI) between repeated examination rounds was analyzed. Current depressive symptoms (assessed by questionnaire) and baseline BMI (for the change in BMI analysis only) were deemed important covariates. Additional analyses were stratified by sex and restricted to long-term use (>= 90 days) and by level of binding affinity to the serotonin reuptake transporter (denoted as hSERT antidepressants). RESULTS: Participants who used selective serotonin reuptake inhibitors (SSRIs, n = 198) had a larger increase in BMI compared to nonusers (+0.74 and +0.23 kg/m(2), respectively, P < .001) between repeated examination rounds. No change in BMI was observed for users of tricyclic antidepressants (n = 146) and other antidepressants (n = 57) compared to nonusers. Weight gain was observed only in women who were treated for >= 90 days with hSERT antidepressants or SSRIs, and not in men (P value for interaction = .002). CONCLUSIONS: Within our study of older adults, hSERT antidepressants were associated with an increased body weight in women, which is supported by the biological function of serotonin in weight control and the differences in serotonergic signaling between males and females. PMID- 26132682 TI - Acupuncture for residual insomnia associated with major depressive disorder: a placebo- and sham-controlled, subject- and assessor-blind, randomized trial. AB - OBJECTIVE: To evaluate the efficacy and safety of acupuncture for residual insomnia and other residual symptoms associated with major depressive disorder (MDD). METHOD: 150 participants having significant insomnia for more than 3 months and a history of MDD (both based on DSM-IV-TR criteria) were recruited from 4 psychiatric outpatient clinics in Hong Kong from May 2011 to August 2013 to receive 9 sessions of treatment over 3 weeks. They were randomized to receive acupuncture, minimal acupuncture, or placebo acupuncture. Primary outcome was sleep diary-derived sleep efficiency. Secondary outcomes included other sleep diary parameters, actigraphy, anxiety and depressive symptoms, daytime functioning, and adverse events. RESULTS: The mean difference in sleep diary derived sleep efficiency at 1-week posttreatment was -1.40 (95% CI, -7.08 to 4.28) between the acupuncture and minimal acupuncture groups and was 3.10 (95% CI, -3.64 to 9.84) between the acupuncture and placebo acupuncture groups. A chi(2) test showed that acupuncture produced a significantly higher proportion of participants achieving sleep-onset latency <= 30 minutes than did minimal acupuncture at 1-week posttreatment (P = .04). However, there was no significant between-group difference in most of the other outcomes. Treatment blinding was successful, as a majority of participants did not know which treatment they had received. CONCLUSIONS: Acupuncture was well tolerated, but the efficacy was only mild and similar to that of minimal acupuncture and placebo acupuncture. A high proportion of patients remained clinically significantly affected by insomnia after treatment. The finding raises certain doubts about the value of acupuncture and underscores the difficulties in the treatment of residual insomnia in MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01707706. PMID- 26132683 TI - Half of obsessive-compulsive disorder cases misdiagnosed: vignette-based survey of primary care physicians. AB - OBJECTIVE: Medical settings are the primary mode of care for mental health problems; physicians' abilities with regard to psychiatric diagnosis and treatment recommendations are therefore essential. While misdiagnosis can occur across all psychiatric conditions, the heterogeneous nature of obsessive compulsive disorder (OCD) may make this condition at an elevated risk for misidentification. The study's aim was to assess primary care physicians' ability to identify OCD. METHOD: The study was cross-sectional in design. An online, vignette-based survey was emailed to 1,172 physicians from 5 major medical hospitals in the Greater New York Area. The email included a link to the survey, which consisted of 1 of 8 randomized OCD vignettes; each vignette focused on one of the following common manifestations of OCD: obsessions regarding aggression, contamination, fear of saying things, homosexuality, pedophilia, religion, somatic concerns, or symmetry. Participants provided diagnostic impressions and treatment recommendations for the individual described in the vignette. Data collection took place from December 10, 2012, through January 18, 2013. RESULTS: Two hundred eight physicians completed the survey. The overall misidentification rate was 50.5%. Vignette type was the strongest predictor of a correct OCD response (Wald chi(2)7 = 40.58; P <.0001). Misidentification rates by vignette were homosexuality (84.6%), aggression (80.0%), saying certain things (73.9%), pedophilia (70.8%), somatic concerns (40.0%), religion (37.5%), contamination (32.3%), and symmetry (3.70%). Participants who misidentified the OCD vignette were less likely to recommend a first-line empirically supported treatment (cognitive-behavioral therapy [CBT] = 46.7%, selective serotonin reuptake inhibitor [SSRI] = 8.6%) compared to participants who correctly identified the OCD vignette (CBT = 66.0%, SSRI = 35.0%). Antipsychotic recommendation rates were elevated among incorrect versus correct responders (12.4% vs 1.9%). CONCLUSIONS: Elevated OCD misdiagnosis rates and the impact of incorrect diagnoses on treatment recommendations highlight the need for greater training regarding OCD symptomatology and empirically supported treatments. PMID- 26132684 TI - Exploring the construct of subjective sleep quality in patients with insomnia. AB - OBJECTIVE: The construct of subjective sleep quality is poorly understood. One widely used measure of subjective sleep quality is the Pittsburgh Sleep Quality Index (PSQI). The role of psychiatric illness in the association between the PSQI and a prospective, sleep diary-derived sleep quality measure (SDSQ) was investigated plus the degree to which the PSQI may reflect mood states. METHOD: A sample of 211 insomnia patients (International Classification of Sleep Disorders, Second Edition) divided by the presence or absence of a comorbid psychiatric disorder (DSM-IV-TR) and recruited between January 2004 and February 2009, completed the PSQI (primary outcome) and 2 weeks of sleep diary monitoring. First, correlations between PSQI and SDSQ were compared; second, regression analyses were used to investigate whether the association between PSQI and SDSQ depends on diagnostic status; third, the differences in sleep quality between the groups, plus the contribution of anxiety and depression in explaining these differences, were explored. RESULTS: The correlation between PSQI and SDSQ was significant only in the nonpsychiatric group (P < .001). The association between PSQI and SDSQ was moderated by diagnostic status: it was weaker in psychiatric patients (P = .047). Patients with psychiatric comorbidity scored significantly higher on the PSQI than those without (P < .001); this difference disappeared after controlling for anxiety. There were no group differences for the SDSQ. CONCLUSIONS: The present findings suggest that (1) psychiatric patients may be more biased in their retrospective sleep quality ratings, and (2) the PSQI total score may reflect sleep-related distress. The use of a prospective sleep diary measure in patients with a psychiatric disorder is recommended. PMID- 26132685 TI - Targeting relational aggression in veterans: the Strength at Home Friends and Family intervention. AB - OBJECTIVE: We evaluated the effectiveness of Strength at Home Friends and Families (SAH-F), a dyadic group intervention to prevent relational aggression and its negative consequences, in a community-based sample of service members/veterans and significant others who reported relational difficulties. METHOD: Participants included 70 veterans and their loved ones. Recruitment was conducted from October 2010 through March 2012. Participants completed an initial assessment that included measures of relational aggression and functioning, depressive symptoms, and posttraumatic stress disorder (PTSD) symptoms. Participants were enrolled in the 10-week SAH-F targeting social information processing mechanisms hypothesized to underlie the relationship between trauma and aggression and were reassessed at program completion and 3 months after intervention. RESULTS: Significant reductions in psychological aggression were seen both at program completion and at 3-month follow-up for both veterans (standardized mean gain effect size [ESsg] = -0.45, P < .05) and significant others (ESsg = -0.30, P < .05). Perpetration of physical aggression remained low after pretreatment and did not increase. Relationship adjustment reported by significant others, but not veterans, indicated a significant improvement from pretreatment to program completion (ESsg = 0.33, P < .05). Significant (P < .05) decreases in depressive symptoms were observed from pretreatment to program completion for veterans (ESsg = -0.30, P < .05) and significant others (ESsg = 0.55, P < .05), and significant decreases in PTSD symptoms were observed from pretreatment to follow-up for veterans and significant others (ESsg = -0.52, P < .05). CONCLUSIONS: Results provide support for the effectiveness of SAH-F in reducing relational aggression in military member/significant other dyads and enhancing relationship quality and mental health. PMID- 26132686 TI - Prosodic and semantic affect perception in remitted patients with bipolar I disorder. AB - OBJECTIVE: Bipolar disorder is associated with impairments in emotion processing that are present during both mood episodes and periods of remission. In this context, most previous studies have investigated facial emotion recognition abilities. In contrast, the current study focused on the perception of prosodic and semantic affect. METHOD: The present study directly contrasted the perception of prosodic and semantic affect in 58 remitted patients meeting DSM-IV criteria for bipolar I disorder and 45 healthy volunteers by using 2 subtests of the Comprehensive Affective Testing System (CATS) and investigated the relationship of prosodic and semantic affect perception with patients' outcomes. Participants were investigated from June 2011 until May 2013. RESULTS: Patients and controls did not differ regarding the recognition of the vocal emotion while ignoring the affective meaning of test trials (CATS 1), but patients significantly more often misinterpreted sad as happy prosody (P = .039). In addition, patients were impaired in recognizing the affective meaning of test trials while ignoring the vocal emotion (CATS 2; P = .052). Again, they significantly more often misinterpreted a sad affective meaning as a happy one (P = .025). However, the findings on misinterpretations did not withstand Bonferroni correction for multiple testing. CATS 1 test performance was negatively correlated with depression scores, whereas a positive association was found between performance on both tests and patients' functioning. Patients indicated a significantly lower quality of life (P < .001); however, multiple mediation analysis revealed that this finding was not mediated by differences in prosodic and/or semantic affect perception between the 2 groups. CONCLUSIONS: Even during periods of remission, patients with bipolar disorder may be impaired in semantic but not prosodic affect perception. Notably, they may frequently misinterpret sadly expressed emotions as happy ones. Our findings underscore the relevance of these deficits in the psychosocial context. PMID- 26132688 TI - The association of childhood trauma and personality disorders with chronic depression: A cross-sectional study in depressed outpatients. AB - OBJECTIVE: Chronic depression has often been associated with childhood trauma. There may, however, be an interaction between personality pathology, childhood trauma, and chronic depression. This interaction has not yet been studied. METHOD: This retrospective analysis is based on 279 patients contacted for a randomized trial in an outpatient psychotherapy center over a period of 18 months from 2010 to 2012. Current diagnoses of a personality disorder and presence of chronic depression were systematically assessed using the Structured Clinical Interview for DSM-IV. Retrospective reports of childhood trauma were collected using the short form of the Childhood Trauma Questionnaire (CTQ-SF). DSM-IV defined chronic depression was the primary outcome. The association between chronic depression, childhood trauma, and personality disorders was analyzed using correlations. Variables that had at least a small effect on correlation analysis were entered into a series of logistic regression analyses to determine the predictors of chronic depression and the moderating effect of childhood trauma. RESULTS: The presence of avoidant personality disorder, but no CTQ-SF scale, was associated with the chronicity of depression (odds ratio [OR] = 2.20, P = .015). The emotional abuse subscale of the CTQ-SF did, however, correlate with avoidant personality disorder (OR = 1.15, P = .000). The level of emotional abuse had a moderating effect on the effect of avoidant personality disorder on the presence of chronic depression (OR = 1.08, P = .004). Patients who did not suffer from avoidant personality disorder had a decreased rate of chronic depression if they retrospectively reported more severe levels of emotional abuse (18.9% vs 39.7%, respectively). CONCLUSIONS: The presence of avoidant personality pathology may interact with the effect of childhood trauma in the development of chronic depression. This has to be confirmed in a prospective study. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01226238. PMID- 26132687 TI - D-Cycloserine facilitation of exposure therapy improves weight regain in patients with anorexia nervosa: a pilot randomized controlled trial. AB - OBJECTIVE: Exposure therapy in anorexia nervosa has preliminarily been shown to be effective for increasing food intake. D-Cycloserine is a glutamatergic N methyl-d-aspartate receptor agonist that has been shown to facilitate the benefits of exposure therapy for anxiety disorders by enhancing the emotional learning in the exposures; therefore, we examined D-cycloserine-facilitation of exposure therapy to increase body mass index (BMI) in patients with anorexia nervosa. METHOD: Participants (N = 36) with anorexia nervosa (diagnosed via DSM IV) were recruited from a partial hospitalization eating disorder clinic between February 2013 and November 2013. Participants were randomly assigned to receive exposure therapy plus D-cycloserine (n = 20) or placebo (n = 16). Participants completed psychoeducation and 4 sessions of exposure therapy, with medication (D cycloserine vs placebo) given prior to the first 3 exposure sessions. They also completed a 1-month follow-up. RESULTS: As hypothesized, participants in the D cycloserine group showed a significantly greater increase in BMI than those in the placebo group (Wilk Lambda = 0.86, F3,32 = 2.20, P = .043, etap(2) = 0.12). D Cycloserine participants gained 3 pounds relative to 0.5 pounds in the placebo group. Both groups experienced significantly decreased anxiety over the course of therapy (Wilk Lambda = 0.80, F3,32 = 3.32, P = .023, etap(2) = 0.20). CONCLUSIONS: This study preliminarily demonstrates that D-cycloserine facilitates exposure therapy for anorexia nervosa, leading to increased weight gain. A potential mechanism is that participants who receive D-cycloserine may generalize learning from within-session exposures to food intake during other similar meals, resulting in sustained increases in BMI. Further research is needed to confirm these findings and test the putative mechanism that generalized learning from exposure therapy can increase BMI and stabilize a healthy weight. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01996644. PMID- 26132689 TI - Clinical risk factors for weight gain during psychopharmacologic treatment of depression: results from 2 large German observational studies. AB - OBJECTIVE: Weight gain during psychopharmacologic treatment has considerable impact on the clinical management of depression, treatment continuation, and risk for metabolic disorders. As no profound clinical risk factors have been identified so far, the aim of our analyses was to determine clinical risk factors associated with short-term weight development in 2 large observational psychopharmacologic treatment studies for major depression. METHOD: Clinical variables at baseline (age, gender, depression psychopathology, anthropometry, disease history, and disease entity) were analyzed for association with percent change in body mass index (BMI; normal range, 18.5 to 25 kg/m(2)) during 5 weeks of naturalistic psychopharmacologic treatment in patients who had a depressive episode as single depressive episode, in the course of recurrent unipolar depression or bipolar disorder according to DSM-IV criteria. 703 patients participated in the Munich Antidepressant Response Signature (MARS) project, an ongoing study since 2002, and 214 patients participated in a study conducted at the University of Muenster from 2004 to 2006 in Germany. RESULTS: Lower BMI, weight-increasing side effects of medication, severity of depression, and psychotic symptoms could be identified as clinical risk factors associated with elevated weight gain during the initial treatment phase of 5 weeks in both studies. Based on these results, a composite risk score for weight gain consisting of BMI <= 25 kg/m(2), Hamilton Depression Rating Scale (17-item) score > 20, presence of psychotic symptoms, and administration of psychopharmacologic medication with potential weight-gaining side effects was highly discriminative for mean weight gain (F4,909 = 26.77, P = 5.14E-21) during short-term psychopharmacologic treatment. CONCLUSIONS: On the basis of our results, depressed patients with low to normal BMI, severe depression, or psychotic symptoms should be considered at higher risk for weight gain during acute antidepressant treatment. We introduce a new risk score that might be considered in psychopharmacologic decisions for the prevention of weight gain and resulting metabolic disorders. PMID- 26132690 TI - Functional versus syndromal recovery in patients with major depressive disorder and bipolar disorder. AB - OBJECTIVE: Many patients with major depressive disorder (MDD) or bipolar disorder (BD) experience impairments in daily life. We investigated whether patients with single-episode MDD (MDD-s), recurrent MDD (MDD-r), and BD differ in functional impairments, whether time since last episode (syndromal state, in 4 categories) contributes to impairment, whether this association is moderated by diagnosis, and the role of depressive symptoms. METHOD: Data were derived from 1,664 participants in the Netherlands Study of Depression and Anxiety (MDD-s, n = 483; MDD-r, n = 1,063; BD, n = 118), from 2006 into 2009. In additional analyses, 530 healthy controls were included. DSM-IV-TR diagnosis and information about syndromal state were based on the Composite International Diagnostic Interview. Psychosocial impairment was assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Adjusted associations between diagnosis, syndromal state, impairment, and depression severity were investigated. RESULTS: Syndromal state not being taken into account, patients with BD experienced more functional impairment than patients with MDD-s or with MDD-r, and in all diagnostic groups, impairments decreased with increasing time since last episode. However, impact of syndromal state on functioning showed a different course between diagnostic groups (mean [SD] WHODAS score: current: MDD s 30.8 [2.8], MDD-r 32.7 [0.9], BD 37.7 [2.1], P = .07; recently remitted: MDD-s 21.7 [3.5], MDD-r 24.0 [1.2], BD 22.1[3.2], P = .7; remitted: MDD-s 10.6 [3.7], MDD-r 21.6 [1.4], BD 19.2 [4.4], P = .02; remitted > 1 year: MDD-s 13.3 [0.6], MDD-r 14.7 [0.5], BD 17.1 [2.2], P = .8). Depression severity accounted for these differences. Moreover, functioning in all remitted patients remained impaired when compared to that in healthy controls. CONCLUSION: Functional recovery may take up to 1 year after syndromal remission in recurrent depressive and bipolar disorder, mainly due to residual depressive symptoms, emphasizing the need for prolonged continuation treatment. PMID- 26132691 TI - Novel approaches to study design and intervention for residual symptoms of MDD. PMID- 26132692 TI - Electroacupuncture in treating residual insomnia associated with depression: lessons learned. PMID- 26132693 TI - What to make of misidentification rates in obsessive-compulsive disorder. PMID- 26132694 TI - There are two sides to every question: exploring the construct of sleep quality. PMID- 26132695 TI - Time for dyadic treatments for low-level partner aggression. PMID- 26132696 TI - Advancements in treating intimate partner violence in veterans. PMID- 26132697 TI - Treatment for depression and the risk of weight gain. PMID- 26132698 TI - Major depressive disorder: treat the disability, not the diagnosis. PMID- 26132699 TI - Distinguishing functional from syndromal recovery: implications for clinical care and research. PMID- 26132700 TI - Dose-Dependent effect of lithium on cognition in mild cognitive impairment. PMID- 26132701 TI - Dr Miskowiak and colleagues reply. PMID- 26132703 TI - Distractor Effect of Auditory Rhythms on Self-Paced Tapping in Chimpanzees and Humans. AB - Humans tend to spontaneously align their movements in response to visual (e.g., swinging pendulum) and auditory rhythms (e.g., hearing music while walking). Particularly in the case of the response to auditory rhythms, neuroscientific research has indicated that motor resources are also recruited while perceiving an auditory rhythm (or regular pulse), suggesting a tight link between the auditory and motor systems in the human brain. However, the evolutionary origin of spontaneous responses to auditory rhythms is unclear. Here, we report that chimpanzees and humans show a similar distractor effect in perceiving isochronous rhythms during rhythmic movement. We used isochronous auditory rhythms as distractor stimuli during self-paced alternate tapping of two keys of an electronic keyboard by humans and chimpanzees. When the tempo was similar to their spontaneous motor tempo, tapping onset was influenced by intermittent entrainment to auditory rhythms. Although this effect itself is not an advanced rhythmic ability such as dancing or singing, our results suggest that, to some extent, the biological foundation for spontaneous responses to auditory rhythms was already deeply rooted in the common ancestor of chimpanzees and humans, 6 million years ago. This also suggests the possibility of a common attentional mechanism, as proposed by the dynamic attending theory, underlying the effect of perceiving external rhythms on motor movement. PMID- 26132704 TI - Evaluation of the Antitumor Efficacy of RNAi-Mediated Inhibition of CDC20 and Heparanase in an Orthotopic Liver Tumor Model. AB - Over 90% of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. This study investigated the antitumor efficacy of the inhibition of cell division cycle protein 20 (CDC20) and heparanase (HPSE) expression in Hepa1-6 mouse hepatoma cells. Cell viability was measured by the MTT assay. Cell cycle was analyzed by cytometry. The invasion assay was performed using the Transwell chamber. The orthotopic liver tumor model was established by inoculating the livers of immunocompetent Kunming mice with Hepa1-6 cells. The MTT assay showed that 50 and 100 nM CDC20 siRNA-1 and HPSE siRNA-2 significantly reduced Hepa1-6 cell viability with the combination of CDC20 and HPSE siRNA being the most effective. Silencing of CDC20 or both CDC20 and HPSE expression significantly induced G2/M phase cell cycle arrest in Hepa1-6 HCC cells. Silencing HPSE expression significantly inhibited the invasion ability of Hepa1-6 cells with the combination of CDC20 and HPSE silencing being more effective than HPSE alone. Silencing CDC20 and HPSE expression significantly inhibited HCC tumor growth in the orthotopic liver tumor model, but the combination was most effective. Silencing CDC20 and HPSE expression activated cell apoptosis and autophagy. In conclusion, targeting inhibition of both CDC20 and HPSE expression is an ideal strategy for HCC therapy. PMID- 26132702 TI - Improved Angiogenesis in Response to Localized Delivery of Macrophage-Recruiting Molecules. AB - Successful engineering of complex organs requires improved methods to promote rapid and stable vascularization of artificial tissue scaffolds. Toward this goal, tissue engineering strategies utilize the release of pro-angiogenic growth factors, alone or in combination, from biomaterials to induce angiogenesis. In this study we have used intravital microscopy to define key, dynamic cellular changes induced by the release of pro-angiogenic factors from polyethylene glycol diacrylate hydrogels transplanted in vivo. Our data show robust macrophage recruitment when the potent and synergistic angiogenic factors, PDGFBB and FGF2 were used as compared with VEGF alone and intravital imaging suggested roles for macrophages in endothelial tip cell migration and anastomosis, as well as pericyte-like behavior. Further data from in vivo experiments show that delivery of CSF1 with VEGF can dramatically improve the poor angiogenic response seen with VEGF alone. These studies show that incorporating macrophage-recruiting factors into the design of pro-angiogenic biomaterial scaffolds is a key strategy likely to be necessary for stable vascularization and survival of implanted artificial tissues. PMID- 26132705 TI - Vibrational Signatures of Solvent-Mediated Deformation of the Ternary Core Ion in Size-Selected [MgSO4Mg(H2O)n=4-11](2+) Clusters. AB - Elucidation of the molecular-level mechanics underlying the dissolution of salts is one of the long-standing, fundamental problems in electrolyte chemistry. Here we follow the incremental structural changes that occur when water molecules are sequentially added to the ternary [MgSO4Mg](2+) ionic assembly using cryogenic vibrational predissociation spectroscopy of the cold, mass-selected [MgSO4Mg(H2O)n=4-11](2+) cluster ions. Although the bare [MgSO4Mg](2+) ion could not be prepared experimentally, its calculated minimum energy structure corresponds to a configuration where the two Mg(2+) ions attach on opposite sides of the central SO4(2-) ion in a bifurcated fashion to yield a D2d symmetry arrangement. Analysis of the observed spectral patterns indicate that water molecules preferentially attach to the flanking Mg(2+) ions for the n <= 7 hydrates, which results in an incremental weakening of the interaction between the ions. Water molecules begin to interact with the sequestered SO4(2-) anion promptly at n = 8, where changes in the band pattern clearly demonstrate that the intrinsic bifurcated binding motif among the ions evolves into quasilinear Mg(2+) O-S arrangements as water molecules H-bond to the now free SO groups. Although condensed-phase MgSO4 occurs with a stable hexahydrate in which water molecules lie between the ion pairs, addition of a sixth water molecule to one of the Mg(2+) ions in the n = 11 cluster occurs with the onset of the second hydration shell such that the cation remains coordinated to one of the SO4(2-) oxygen atoms. PMID- 26132706 TI - Editorial: The Rise of the Asterisk: One Step to Facilitate Team Science. PMID- 26132709 TI - Strategies to Improve Survival From Cardiac Arrest: A Report From the Institute of Medicine. PMID- 26132711 TI - Erratum: Do Learning Effects Lead to Path Dependencies in Hospitals? Study of the Effects on Reorganisation Processes. PMID- 26132710 TI - Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported. AB - BACKGROUND: It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. OBJECTIVE: We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status. METHODS: We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines. Inflammatory cytokines were investigated using a Th1/Th2 assay including 14 chemokines and cytokines; tissue concentrations were normalized according to tissue weight and total protein concentration. Individual cytokines and multivariate inflammatory profiles were compared between biopsy sites and between patients and controls. RESULTS: We found significantly higher concentrations of Th2 cytokines in nasal polyps compared to inferior turbinate and bronchial biopsies. In addition, we showed that the inflammatory profile of nasal polyps and bronchial biopsies correlated significantly (p<0.01). From the Th2 cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma. CONCLUSION: Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally, this study indicates for the first time that nasal polyps potentially play an important role in the airway inflammation rather than being a secondary phenomenon. PMID- 26132712 TI - Population genetic structure and approximate Bayesian computation analyses reveal the southern origin and northward dispersal of the oriental fruit moth Grapholita molesta (Lepidoptera: Tortricidae) in its native range. AB - The oriental fruit moth (OFM) Grapholita molesta is one of the most destructive orchard pests. Assumed to be native to China, the moth is now distributed throughout the world. However, the evolutionary history of this moth in its native range remains unknown. In this study, we explored the population genetic structure, dispersal routes and demographic history of the OFM in China and South Korea based on mitochondrial genes and microsatellite loci. The Mantel test indicated a significant correlation between genetic distance and geographical distance in the populations. Bayesian analysis of population genetic structure (baps) identified four nested clusters, while the geneland analysis inferred five genetic groups with spatial discontinuities. Based on the approximate Bayesian computation approach, we found that the OFM was originated from southern China near the Shilin area of Yunnan Province. The early divergence and dispersal of this moth was dated to the Penultimate glaciation of Pleistocene. Further dispersal from southern to northern region of China occurred before the last glacial maximum, while the expansion of population size in the derived populations in northern region of China occurred after the last glacial maximum. Our results indicated that the current distribution and structure of the OFM were complicatedly influenced by climatic and geological events and human activities of cultivation and wide dissemination of peach in ancient China. We provide an example on revealing the origin and dispersal history of an agricultural pest insect in its native range as well as the underlying factors. PMID- 26132713 TI - Rapid Aluminum Nanoparticle Production by Milling in NH3 and CH3NH2 Atmospheres: An Experimental and Theoretical Study. AB - Ball milling of aluminum in gaseous atmospheres of ammonia and monomethylamine (MMA) was found to produce particles in the 100 nm size range with high efficiency. A combination of mass spectrometry, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis with mass spectrometric product analysis (TGA MS), scanning electron microscopy (SEM), infrared spectroscopy, and dynamic light scattering (DLS) was used to study the particles and the chemical interactions responsible for particle production. To help understand the nature of the surface chemistry, high level quantum chemical calculations were performed to predict the structures and energetics for binding and reactions of NH3 and MMA on aluminum surfaces. Both NH3 and MMA react with aluminum under milling conditions, producing H2 and other gaseous products, and leaving the surfaces functionalized. The surface functionalization enhances size reduction by reducing the surface free energy and the tendency toward mechanochemical welding. For both NH3 and MMA, the particle cores are metallic aluminum, but the surface chemical properties are quite different. The ammonia-milled particles are capped by an AlNxOyHz layer ~10 nm thick, which passivates the particles. The MMA-milled particles are capped with a thinner passivating layer, such that they are pyrophoric in air and react with N2 at elevated temperatures. PMID- 26132714 TI - Quantitation of Endothelial Cell Adhesiveness In Vitro. AB - One of the cardinal processes of inflammation is the infiltration of immune cells from the lumen of the blood vessel to the surrounding tissue. This occurs when endothelial cells, which line blood vessels, become adhesive to circulating immune cells such as monocytes. In vitro measurement of this adhesiveness has until now been done by quantifying the total number of monocytes that adhere to an endothelial layer either as a direct count or by indirect measurement of the fluorescence of adherent monocytes. While such measurements do indicate the average adhesiveness of the endothelial cell population, they are confounded by a number of factors, such as cell number, and do not reveal the proportion of endothelial cells that are actually adhesive. Here we describe and demonstrate a method which allows the enumeration of adhesive cells within a tested population of endothelial monolayer. Endothelial cells are grown on glass coverslips and following desired treatment are challenged with monocytes (that may be fluorescently labeled). After incubation, a rinsing procedure, involving multiple rounds of immersion and draining, the cells are fixed. Adhesive endothelial cells, which are surrounded by monocytes are readily identified and enumerated, giving an adhesion index that reveals the actual proportion of endothelial cells within the population that are adhesive. PMID- 26132715 TI - Opioid Use Trajectories, Injection Drug Use, and Hepatitis C Virus Risk Among Young Adult Immigrants from the Former Soviet Union Living in New York City. AB - Available evidence suggests that young former Soviet Union immigrants in New York City have high rates of non-medical prescription opioid and heroin use, drug injection and injection-related risk behavior, making them vulnerable to hepatitis C virus (HCV)/human immunodeficiency virus (HIV) infection, overdose and associated harms. This group has been the focus of little research, however. This paper presents quantitative and qualitative data from 80 former Soviet immigrants (ages 18-29) to characterize their opioid use trajectories, injection risk behavior, HCV/HIV testing histories and self-reported HCV/HIV serostatus, and provides clinically meaningful data to inform tailored education, prevention and harm reduction interventions. PMID- 26132716 TI - Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes. AB - BACKGROUND: At birth, infants' lungs are fluid-filled; this fluid must be replaced by air to allow for effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume in the lungs. OBJECTIVES: To assess the efficacy of initial sustained (> one second duration) lung inflation compared to standard inflations (<= one second) in newly born infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We searched on PubMed (1966 to 1 February 2015), EMBASE (1980 to 1 February 2015) and the Cochrane Central Register of Controlled Trials (the Cochrane Library 2015). No language restrictions were applied. We searched the abstracts of the Pediatric Academic Societies (PAS) from 2000 to 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing giving initial sustained lung inflations (SLI) vs. standard inflations to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed methodological quality of the included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up and handling of outcome data). We evaluated the treatment effect using a fixed-effect model using risk ratio for categorical data and using mean, standard deviation (SD) and weighted mean difference (WMD) for continuous data. MAIN RESULTS: Two trials enrolling 352 infants met our inclusion criteria. There were no differences in the rates of mortality during hospitalisation (RR 1.59, 95% CI 0.81 to 3.10; two trials, 352 infants), intubation in the first three days of life (RR 0.85, 95% CI 0.72 to 1.02; two trials, 352 infants) or chronic lung disease (RR 1.06, 95% CI 0.79 to 1.42; two trials, 349 infants) between infants who received sustained versus standard inflations. The rate of patent ductus arteriosus (reported as need for pharmacological treatment) was higher in the sustained inflation group (RR 1.27, 95% CI 1.03 to 1.56; two trials, 352 infants). AUTHORS' CONCLUSIONS: At present there is insufficient evidence from clinical trials to determine the efficacy and safety of initial sustained lung inflation for newborn infants resuscitated with PPV. RCTs comparing PPV with and without sustained inflations at neonatal resuscitation are warranted. PMID- 26132718 TI - Cup-like blasts in B-lymphoblastic leukaemia. PMID- 26132717 TI - Influence of Partner Type on Acceptability and Likelihood of Use of a Rectal Microbicide Among Young Men Who Have Sex With Men in the United States and Puerto Rico. AB - This study examined how acceptability of placebo gel with receptive anal intercourse (RAI) and likelihood of future rectal microbicide use varied across partner types. Because no rectal microbicide is available yet, use of placebo permitted the study of gel use behavior in real-life circumstances. A total of 87 men who have sex with men (MSM) aged 18 to 30 years inserted placebo gel rectally before RAI during 12 weeks. Using mixed-methods design, participants completed a behavioral questionnaire and in-depth interview. In all, 62 men (71.3%) reported gel use with a lover (i.e., spouse equivalent, boyfriend), 32 (36.8%) with a one night stand (i.e., man with whom you had sex once), and 29 (33.3%) with an "other" male partner. While gel acceptability was high across partner types, use with lovers was facilitated by trust and familiarity; yet trust made participants believe protection was less necessary. Conversely, participants expressed high likelihood of using gel with one-night stands, whom they perceived as riskier; yet they felt less comfortable discussing gel with them, often resorting to covert use or forgoing gel. A successful microbicide will be positioned as a sexual pleasure enhancer so that men can present it to their lovers and other partners as a gel that improves sex and secondarily prevents human immunodeficiency virus (HIV). PMID- 26132719 TI - Recent advances in alternative counter electrode materials for Co-mediated dye sensitized solar cells. AB - Recently, considerable attention has been paid to dye-sensitized solar cells (DSSCs) which are based on Co(2+)/Co(3+) redox shuttles, because of their unparalleled merits including higher redox potential, reduced corrosiveness towards metallic conductors, low costs and high power conversion efficiencies (PCE) (13%). The counter electrode (CE) is an essential component in DSSCs, and plays a crucial role in catalyzing Co(3+) ion reduction in Co-based DSSCs. In this mini-review, we review recent developments in CE materials for Co-mediated DSSCs including: noble metal platinum (Pt), carbon materials, transition metal compounds (TMCs), polymers, and their corresponding hybrids, highlighting important contributions worldwide that promise low cost, efficient, and robust Co mediated DSSC systems. Additionally, the crucial challenges associated with employing these low-cost CE catalysts for Co-based redox couples in DSSCs are stressed. PMID- 26132720 TI - Antioxidants protect calsequestrin-1 knockout mice from halothane- and heat induced sudden death. AB - BACKGROUND: Mice lacking calsequestrin-1 (CASQ1-null), a Ca-binding protein that modulates the activity of Ca release in the skeletal muscle, exhibit lethal hypermetabolic episodes that resemble malignant hyperthermia in humans when exposed to halothane or heat stress. METHODS: Because oxidative species may play a critical role in malignant hyperthermia crises, we treated CASQ1-null mice with two antioxidants, N-acetylcysteine (NAC, Sigma-Aldrich, Italy; provided ad libitum in drinking water) and (+/-)-6-hydroxy-2,5,7,8-tetramethylchromane-2 carboxylic acid (Trolox, Sigma-Aldrich; administered by intraperitoneal injection), before exposure to halothane (2%, 1 h) or heat (41 degrees C, 1 h). RESULTS: NAC and Trolox significantly protected CASQ1-null mice from lethal episodes, with mortality being 79% (n = 14), 25% (n = 16), and 20% (n = 5) during halothane exposure and 86% (n = 21), 29% (n = 21), and 33% (n = 6) during heat stress in untreated, NAC-treated, and Trolox-treated mice, respectively. During heat challenge, an increase in core temperature in CASQ1-null mice (42.3 degrees +/- 0.1 degrees C, n=10) was significantly reduced by both NAC and Trolox (40.6 degrees +/- 0.3 degrees C, n = 6 and 40.5 degrees +/- 0.2 degrees C, n = 6). NAC treatment of CASQ1-null muscles/mice normalized caffeine sensitivity during in vitro contracture tests, Ca transients in single fibers, and significantly reduced the percentage of fibers undergoing rhabdomyolysis (37.6 +/- 2.5%, 38/101 fibers in 3 mice; 11.6 +/- 1.1%, 21/186 fibers in 5 mice). The protective effect of antioxidant treatment likely resulted from mitigation of oxidative stress, because NAC reduced mitochondrial superoxide production, superoxide dismutase type-1 expression, and 3-nitrotyrosine expression, and increased both reduced glutathione and reduced glutathione/oxidized glutathione ratio. CONCLUSION: These studies provide a deeper understanding of the mechanisms that underlie hyperthermic crises in CASQ1-deficient muscle and demonstrate that antioxidant pretreatment may prevent them. PMID- 26132722 TI - Repetitive Implantable Cardioverter Defibrillator Shocks: What is the Mechanism? PMID- 26132721 TI - AMPK Phosphorylation Modulates Pain by Activation of NLRP3 Inflammasome. AB - AIMS: Impairment in adenosine monophosphate-activated protein kinase (AMPK) activity and NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation are associated with several metabolic and inflammatory diseases. In this study, we investigated the role of AMPK/NLRP3 inflammasome axis in the molecular mechanism underlying pain perception. RESULTS: Impairment in AMPK activation induced by compound C or sunitinib, two AMPK inhibitors, provoked hyperalgesia in mice (p<0.001) associated with marked NLRP3 inflammasome protein activation and increased serum levels of interleukin-1beta (IL-1beta) (24.56+/ 0.82 pg/ml) and IL-18 (23.83+/-1.882 pg/ml) compared with vehicle groups (IL 1beta: 8.15+/-0.44; IL-18: 4.92+/-0.4). This effect was rescued by increasing AMPK phosphorylation via metformin treatment (p<0.001), caloric restriction diet (p<0.001), or NLRP3 inflammasome genetic inactivation using NLRP3 knockout (nlrp3(-/-)) mice (p<0.001). Deficient AMPK activation and overactivation of NLRP3 inflammasome axis were also observed in blood cells from patients with fibromyalgia (FM), a prevalent human chronic pain disease. In addition, metformin treatment (200 mg/daily), which increased AMPK activation, restored all biochemical alterations examined by us in blood cells and significantly improved clinical symptoms, such as, pain, fatigue, depression, disturbed sleep, and tender points, in patients with FM. INNOVATION AND CONCLUSIONS: These data suggest that AMPK/NLRP3 inflammasome axis participates in chronic pain and that NLRP3 inflammasome inhibition by AMPK modulation may be a novel therapeutic target to fight against chronic pain and inflammatory diseases as FM. PMID- 26132723 TI - Conferring high-temperature tolerance to nontransgenic tomato scions using graft transmission of RNA silencing of the fatty acid desaturase gene. AB - We investigated graft transmission of high-temperature tolerance in tomato scions to nontransgenic scions from transgenic rootstocks, where the fatty acid desaturase gene (LeFAD7) was RNA-silenced. Tomato was transformed with a plasmid carrying an inverted repeat of LeFAD7 by Agrobacterium. Several transgenic lines showed the lower amounts of LeFAD7 RNA and unsaturated fatty acids, while nontransgenic control did not, and siRNA was detected in the transgenic lines, but not in control. These lines grew under conditions of high temperature, while nontransgenic control did not. Further, the nontransgenic plants were grafted onto the silenced transgenic plants. The scions showed less of the target gene RNA, and siRNA was detected. Under high-temperature conditions, these grafted plants grew, while control grafted plants did not. Thus, it was shown that high temperature tolerance was conferred in the nontransgenic scions after grafting onto the silenced rootstocks. PMID- 26132725 TI - Voluntary or Mandatory? The Valence Framing Effect of Attitudes Regarding HPV Vaccination. AB - This study addresses the issue of valence framing effect in the context of immunization, a preventive behavior often addressed by the equation of benefit versus risk. The authors examined how framing (support vs. oppose) the issue of HPV vaccination in Israel's immunization routine affects attitudes regarding vaccine regulations. The study also examined issue involvement as a moderator of valence framing effect. The results demonstrate that participants in the positive framing condition tended to express greater support for voluntary immunization than participants in the negative framing condition (77.5% and 48.5%, respectively). Among those who supported the mandatory HPV immunization policy, the negative framing condition was more prominent than the positive condition (51.5% and 22.5%, respectively). The analysis of interaction between valence framing and issue involvement showed that the latter tends to moderate the direct effect of framing on attitudes towards vaccination. Findings indicate that even attitudes towards such consequential preventive behaviors as vaccination could be affected by different framing of the issue, especially for those who are less involved. Implications of predilection for freedom of choice regarding vaccination are also discussed. PMID- 26132724 TI - Treatment of Young People With Antipsychotic Medications in the United States. AB - IMPORTANCE: Despite concerns about rising treatment of young people with antipsychotic medications, little is known about trends and patterns of their use in the United States. OBJECTIVE: To describe antipsychotic prescription patterns among young people in the United States, focusing on age and sex. DESIGN, SETTING, AND PARTICIPANTS: A retrospective descriptive analysis of antipsychotic prescriptions among patients aged 1 to 24 years was performed with data from calendar years 2006 (n = 765,829), 2008 (n = 858,216), and 2010 (n = 851,874), including a subset from calendar year 2009 with service claims data (n = 53,896). Data were retrieved from the IMS LifeLink LRx Longitudinal Prescription database, which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population. MAIN OUTCOMES AND MEASURES: The percentage of young people filling 1 or more antipsychotic prescriptions during the study year by sex and age group (younger children, 1-6 years; older children, 7-12 years; adolescents, 13-18 years; and young adults, 19-24 years) was calculated. Among young people with antipsychotic use, percentages with specific clinical psychiatric diagnoses and 1 or more antipsychotic prescriptions from a psychiatrist and from a child and adolescent psychiatrist were also determined. RESULTS: The percentages of young people using antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults. In 2010, males were more likely than females to use antipsychotics, especially during childhood and adolescence: 0.16% vs 0.06% for younger children, 1.20% vs 0.44% for older children, 1.42% vs 0.95% for adolescents, and 0.88% vs 0.81% for young adults. Among young people treated with antipsychotics in 2010, receiving a prescription from a psychiatrist was less common among younger children (57.9%) than among other age groups (range, 70.4%-77.9%). Approximately 29.3% of younger children treated with antipsychotics in 2010 received 1 or more antipsychotic prescriptions from a child and adolescent psychiatrist. Among young people with claims for mental disorders in 2009 who were treated with antipsychotics, the most common diagnoses were attention-deficit/hyperactivity disorder in younger children (52.5%), older children (60.1%), and adolescents (34.9%) and depression in young adults (34.5%). CONCLUSIONS AND RELEVANCE: Antipsychotic use increased from 2006 to 2010 for adolescents and young adults but not for children aged 12 years or younger. Peak antipsychotic use in adolescence, especially among boys, and clinical diagnosis patterns are consistent with management of developmentally limited impulsive and aggressive behaviors rather than psychotic symptoms. PMID- 26132726 TI - Emergency Food Supplies in Food Secure Households. AB - Introduction Limited food supply paired with reduced access to food during emergency disasters can lead to malnutrition. To date, research evaluating the adequacy of household emergency food supplies relies on self-reported data from surveys and has not been measured objectively in households in the United States. The main objective of this study was to describe household calorie availability and nutrient density in a normal situation and to project changes that could occur when emergencies (eg, natural disasters) restrict replenishment of food supplies and disrupt water and/or energy needed for food preparation and storage. Hypothesis The calorie availability of the food supply within households in New Jersey (USA) is anticipated to be well above the recommended 3-day period. However, it is anticipated that the nutritional density of the food supply within these households will be negative. Additionally, the disaster-related factors that diminish the ability to consume stored food (eg, lack of water, power for cooking, and/or proper storage) will further reduce the caloric and nutritional adequacy of the household food supply. METHODS: The household food supplies of 100 food secure families in New Jersey were inventoried at a non-emergency point in time. The number of days that the inventoried food supply would provide all household members 100% of the daily value (DV) for calories and other nutrients was determined. Additionally, the effects of water and power shortages on nutritional availability of household food supply were estimated. RESULTS: The households had an average of 33.16 days (SD=21.97; range=8.14-125.17 days) of calories at 100% DV for all household members. Lack of water, energy for cooking, or both would render a decrease in the total household calories by 28%, 35%, or 38%, respectively. Loss of power for greater than five days would reduce availability of household calories by 27%. A positive nutrient density was observed with and without the food-related resources of water and power. CONCLUSION: The mean food supply within the sampled households exceeds the current emergency preparedness recommendations, even when considering specific nutrients and emergency-related factors that affect ability to consume the food supply. Cross-sectional observation of the household food supply of food secure families in New Jersey reveals adequate dietary-based emergency preparedness and low vulnerability to emergency-induced food insecurity. PMID- 26132727 TI - Significance of P-cadherin overexpression and possible mechanism of its regulation in intrahepatic cholangiocarcinoma and pancreatic cancer. AB - It has become evident that P-cadherin, one of the classical cadherins, contributes to the malignant behavior of several types of cancer. In this study, we analyzed the expression of P-cadherin and its clinicopathological and prognostic values in intrahepatic cholangiocarcinoma (ICC) and pancreatic cancer. Furthermore, we investigated the functional role of P-cadherin in these cancer cells by knockdown and overexpression in vitro and by analyzing the correlation between the P-cadherin expression and its promoter methylation status. Thirty of 59 ICC cases (51%) and 36 of 73 pancreatic cancer cases (49%) stained positive for P-cadherin with mainly membranous distribution in tumor cells by immunohistochemistry. P-cadherin expression was significantly correlated with several clinicopathological factors, which reflect tumor behavior, and was identified as an independent adverse prognostic factor for disease-free survival in patients with ICC (relative risk [RR] 2.93, P = 0.04) and pancreatic cancer (RR 2.68, P = 0.005) via multivariate analyses. P-cadherin downregulation by siRNA suppressed migration and invasion, and P-cadherin overexpression induced the opposite effects in both ICC and pancreatic cancer cells, without any effects on cell proliferation. P-cadherin expression was related to its promoter methylation status in both cell lines and cancer tissues. In summary, P-cadherin overexpression may serve as a useful biomarker of invasive phenotype and poor prognosis; P-cadherin expression was found to be regulated by its promoter methylation. These results suggest that P-cadherin represents a novel therapeutic target for the treatment of ICC and pancreatic cancer. PMID- 26132728 TI - The Relationship among Carotid Artery Remodeling, Cardiac Geometry, and Serum N Terminal Pro-B-Type Natriuretic Peptide Level in Asymptomatic Asians: Sex Differences and Longitudinal GEE Study. AB - BACKGROUND: Carotid artery remodeling is known to be associated with a variety of cardiovascular diseases. However, there is limited information regarding gender differences in carotid remodeling. We sought to investigate the associations among blood pressure (BP), carotid artery remodeling and cardiac geometries, and further explore gender differences. MATERIALS AND METHODS: In a large cohort of asymptomatic adults undergoing routine health screening with repeated observations, we related measures of carotid artery diameter (CCAD) to various BP components, cardiac geometries and blood N-terminal pro-brain natriuretic peptide (NT-proBNP) level, both from baseline cross-sectional and longitudinal dataset using generalized estimating equations (GEE). RESULTS: A total of 2,914 person visits (baseline: n=998, mean age: 47 +/- 8.9 years, 34% female) were studied (median: 6 +/- 1.73 years follow up). We observed that CCAD was larger in men (p<0.01) and positively related to baseline age or all blood pressure components (including systolic BP [SBP], diastolic BP [DBP] and pulse pressure [PP], all p<0.01) even after accounting for clinical covariates, which did not change significantly at follow up (repeat-visit longitudinal GEE models). At baseline, per each increased unit of CCAD was associated with elevated LV mass index (beta coef: 6.72, with odds ratio [OR]: 1.47, 95% CI: 1.06 to 2.07 for ventricular hypertrophy; AUROC: 0.65, CCAD cut-off: 7.25mm) and NT-proBNP (beta-coef: 5.35, OR: 4.22, 95% CI: 1.42 to 12.6 for >=300pg/mL; AUROC: 0.79, CCAD cut-off: 7.95mm, all p<0.05), which remained significant in multi-variate and longitudinal models. There was a prominent sex interaction (p for interaction with age and systolic BP: 0.004 and 0.028 respectively), where the longitudinal associations of age and systolic BP with increasing CCAD as more pronounced in women than men. CONCLUSION: These data demonstrated that carotid artery remodeling may parallel subclinical biomarker of cardiac dysfunction, and further showed greater effects of aging and higher blood pressure on such remodeling process in women than men. Further study is warranted to understand how this predisposition of elderly hypertensive women to vascular remodeling may play a role in clinical settings. PMID- 26132729 TI - Life-Threatening Abnormal Behavior Incidence in 10-19 Year Old Patients Administered Neuraminidase Inhibitors. AB - Much discussion has surrounded the association between the administration of neuraminidase inhibitors (NI) and severe abnormal behaviors, including sudden running away and jumping from a high place, which can be life-threatening if no one intervenes. Using data on the number of abnormal behaviors and patients who had been prescribed NI in Japan, we calculated the incidence rate of severe abnormal behaviors among influenza patients who had been prescribed NI. Then, we evaluated the relative risk between the four types of NI on severe abnormal behavior. We found no significant difference in the incidence rates of abnormal behavior by the type of NI. Results implicate that the current policy of package inserts, which warn physicians that patients who were administered ANY type of NI might exhibit abnormal behavior, seems to be appropriate. PMID- 26132730 TI - Dendritic Cell-Mediated Phagocytosis but Not Immune Activation Is Enhanced by Plasmin. AB - Removal of dead cells in the absence of concomitant immune stimulation is essential for tissue homeostasis. We recently identified an injury-induced protein misfolding event that orchestrates the plasmin-dependent proteolytic degradation of necrotic cells. As impaired clearance of dead cells by the innate immune system predisposes to autoimmunity, we determined whether plasmin could influence endocytosis and immune cell stimulation by dendritic cells - a critical cell that links the innate and adaptive immune systems. We find that plasmin generated on the surface of necrotic cells enhances their phagocytic removal by human monocyte-derived dendritic cells. Plasmin also promoted phagocytosis of protease-resistant microparticles by diverse mouse dendritic cell sub-types both in vitro and in vivo. Together with an increased phagocytic capacity, plasmin treated dendritic cells maintain an immature phenotype, exhibit reduced migration to lymph nodes, increase their expression/release of the immunosuppressive cytokine TGF-beta, and lose their capacity to mount an allogeneic response. Collectively, our findings support a novel role for plasmin formed on dead cells and other phagocytic targets in maintaining tissue homeostasis by increasing the phagocytic function of dendritic cells while simultaneously decreasing their immunostimulatory capacity consistent with producing an immunosuppressive state. PMID- 26132731 TI - Canonical Single Nucleotide Polymorphisms (SNPs) for High-Resolution Subtyping of Shiga-Toxin Producing Escherichia coli (STEC) O157:H7. AB - The objective of this study was to develop a canonical, parsimoniously informative SNP panel for subtyping Shiga-toxin producing Escherichia coli (STEC) O157:H7 that would be consistent with epidemiological, PFGE, and MLVA clustering of human specimens. Our group had previously identified 906 putative discriminatory SNPs, which were pared down to 391 SNPs based on their prevalence in a test set. The 391 SNPs were screened using a high-throughput form of TaqMan PCR against a set of clinical isolates that represent the most diverse collection of O157:H7 isolates from outbreaks and sporadic cases examined to date. Another 30 SNPs identified by others were also screened using the same method. Two additional targets were tested using standard TaqMan PCR endpoint analysis. These 423 SNPs were reduced to a 32 SNP panel with the almost the same discriminatory value. While the panel partitioned our diverse set of isolates in a manner that was consistent with epidemiological data and PFGE and MLVA phylogenies, it resulted in fewer subtypes than either existing method and insufficient epidemiological resolution in 10 of 47 clusters. Therefore, another round of SNP discovery was undertaken using comparative genomic resequencing of pooled DNA from the 10 clusters with insufficient resolution. This process identified 4,040 potential SNPs and suggested one of the ten clusters was incorrectly grouped. After its removal, there were 2,878 SNPs, of which only 63 were previously identified and 438 occurred across multiple clusters. Among highly clonal bacteria like STEC O157:H7, linkage disequilibrium greatly limits the number of parsimoniously informative SNPs. Therefore, it is perhaps unsurprising that our panel accounted for the potential discriminatory value of numerous other SNPs reported in the literature. We concluded published O157:H7 SNPs are insufficient for effective epidemiological subtyping. However, the 438 multi-cluster SNPs we identified may provide the additional information required. PMID- 26132732 TI - Prescribed 3-D Direct Writing of Suspended Micron/Sub-micron Scale Fiber Structures via a Robotic Dispensing System. AB - A 3-axis dispensing system is utilized to control the initiating and terminating fiber positions and trajectory via the dispensing software. The polymer fiber length and orientation is defined by the spatial positioning of the dispensing system 3-axis stages. The fiber diameter is defined by the prescribed dispense time of the dispensing system valve, the feed rate (the speed at which the stage traverses from an initiating to a terminating position), the gauge diameter of the dispensing tip, the viscosity and surface tension of the polymer solution, and the programmed drawing length. The stage feed rate affects the polymer solution's evaporation rate and capillary breakup of the filaments. The dispensing system consists of a pneumatic valve controller, a droplet-dispensing valve and a dispensing tip. Characterization of the direct write process to determine the optimum combination of factors leads to repeatedly acquiring the desired range of fiber diameters. The advantage of this robotic dispensing system is the ease of obtaining a precise range of micron/sub-micron fibers onto a desired, programmed location via automated process control. Here, the discussed self-assembled micron/sub-micron scale 3D structures have been employed to fabricate suspended structures to create micron/sub-micron fluidic devices and bioengineered scaffolds. PMID- 26132733 TI - Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module. AB - Undergraduate biology students are required to learn, understand and apply a variety of cellular and molecular biology concepts and techniques in preparation for biomedical, graduate and professional programs or careers in science. To address this, a simple laboratory module was devised to teach the concepts of cell division, cellular communication and cancer through the application of animal cell culture techniques. Here the mouse mammary tumor (MMT) cell line is used to model for breast cancer. Students learn to grow and characterize these animal cells in culture and test the effects of traditional and non-traditional chemotherapy agents on cell proliferation. Specifically, students determine the optimal cell concentration for plating and growing cells, learn how to prepare and dilute drug solutions, identify the best dosage and treatment time course of the antiproliferative agents, and ascertain the rate of cell death in response to various treatments. The module employs both a standard cell counting technique using a hemocytometer and a novel cell counting method using microscopy software. The experimental procedure lends to open-ended inquiry as students can modify critical steps of the protocol, including testing homeopathic agents and over-the counter drugs. In short, this lab module requires students to use the scientific process to apply their knowledge of the cell cycle, cellular signaling pathways, cancer and modes of treatment, all while developing an array of laboratory skills including cell culture and analysis of experimental data not routinely taught in the undergraduate classroom. PMID- 26132734 TI - The Role of Concentration Dependent Static Permittivity of Electrolyte Solutions in the Debye-Huckel Theory. AB - The Debye-Huckel theory has been extended to allow for arbitrary concentration dependence of the electrolyte solution static permittivity. The theory follows the lines advanced by Erich Huckel ( Huckel, E. Phys. Z. 1925, 26, 93) but gives rise to more general and lucid results. New theoretical expressions have been obtained for the excess free energy of solution, activity coefficient of water and mean ionic activity coefficient. The thermodynamic functions contain two terms representing interionic interactions and ion-water (solvation) interactions. The theory has been applied to calculate the activity coefficients of components in the aqueous solutions of alkali metal chlorides from LiCl to CsCl at ambient conditions making use of permittivities taken from experimental dielectric relaxation studies. Calculations without parameter adjustment have demonstrated a semiquantitative agreement with experimental data, reproducing both the nonmonotonic concentration dependence of the activity coefficients and the ordering of activity coefficients for the salts with different cations. A good agreement with experimental data is obtained for the aqueous solutions of LiCl in the concentration range up to 10 mol/kg. The nonmonotonic concentration dependence of activity coefficients is explained as a result of a balance between the effect of interionic interactions and the solvation contribution which appears quite naturally in the framework of the Debye-Huckel approach after incorporation of variable permittivity of solution. PMID- 26132736 TI - A new designed hydrazine group-containing ruthenium complex used for catalytic hydrogenation of esters. AB - A hydrazine group-containing nitrogen-phosphine ligand and corresponding ruthenium complexes were synthesized. When these complexes were used for hydrogenation of esters, excellent performance was observed (TON up to 17, 200). A wide substrate scope was suitable for this catalytic system. PMID- 26132735 TI - Effects of complement activation on allograft injury. AB - PURPOSE OF REVIEW: To summarize the current knowledge regarding mechanisms linking the complement system to transplant injury, highlighting findings reported since 2013. RECENT FINDINGS: Building upon the documentation that complement activation is a pathogenic mediator of posttransplant ischemia reperfusion injury, emerging evidence from animal models indicates that blocking either the classical or lectin pathways attenuates ischemia-reperfusion injury. Immune cell-derived and locally activated complement, including intracellular C3, positively modulates alloreactive T-cell activation and expansion, whereby simultaneously inhibiting regulatory T-cell induction and function, and together promoting transplant rejection. Although alloantibody-initiated complement activation directly injures target cells, complement-dependent signals activate endothelial cells to facilitate T-cell-dependent inflammation. Complement activation within allografts contributes to progressive chronic injury and fibrosis. SUMMARY: The complement cascade, traditionally considered to be relevant to transplantation only as an effector mechanism of antibody-initiated allograft injury, is now understood to damage the allograft through multiple mechanisms. Complement activation promotes posttransplant ischemia-reperfusion injury, formation and function of alloantibody, differentiation and function of alloreactive T cells, and contributes to chronic progressive allograft failure. The recognition that complement affects transplant injury at many levels provides a foundation for targeting complement as a therapy to prolong transplant survival and improve patient health. PMID- 26132737 TI - A Genetic Porcine Model of Cancer. AB - The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic "oncopig" line encoding Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRASG12D and TP53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into immunocompromised mice. Finally, injection of AdCre directly into these oncopigs led to the rapid and reproducible tumor development of mesenchymal origin. Transgenic animals receiving AdGFP (green fluorescent protein) did not have any tumor mass formation or altered histopathology. This oncopig line could thus serve as a genetically malleable model for potentially a wide spectrum of cancers, while controlling for temporal or spatial genesis, which should prove invaluable to studies previously hampered by the lack of a large animal model of cancer. PMID- 26132738 TI - Optogenetic Stimulation of Neural Grafts Enhances Neurotransmission and Downregulates the Inflammatory Response in Experimental Stroke Model. AB - Compelling evidence suggests that transplantation of neural stem cells (NSCs) from multiple sources ameliorates motor deficits after stroke. However, it is currently unknown to what extent the electrophysiological activity of grafted NSC progeny participates in the improvement of motor deficits and whether excitatory phenotypes of the grafted cells are beneficial or deleterious to sensorimotor performances. To address this question, we used optogenetic tools to drive the excitatory outputs of the grafted NSCs and assess the impact on local circuitry and sensorimotor performance. We genetically engineered NSCs to express the Channelrhodopsin-2 (ChR2), a light-gated cation channel that evokes neuronal depolarization and initiation of action potentials with precise temporal control to light stimulation. To test the function of these cells in a stroke model, rats were subjected to an ischemic stroke and grafted with ChR2-NSCs. The grafted NSCs identified with a human-specific nuclear marker survived in the peri-infarct tissue and coexpressed the ChR2 transgene with the neuronal markers TuJ1 and NeuN. Gene expression analysis in stimulated versus vehicle-treated animals showed a differential upregulation of transcripts involved in neurotransmission, neuronal differentiation, regeneration, axonal guidance, and synaptic plasticity. Interestingly, genes involved in the inflammatory response were significantly downregulated. Behavioral analysis demonstrated that chronic optogenetic stimulation of the ChR2-NSCs enhanced forelimb use on the stroke-affected side and motor activity in an open field test. Together these data suggest that excitatory stimulation of grafted NSCs elicits beneficial effects in experimental stroke model through cell replacement and non-cell replacement, anti inflammatory/neurotrophic effects. PMID- 26132739 TI - EphB4 Promotes Osteogenesis of CTLA4-Modified Bone Marrow-Derived Mesenchymal Stem Cells Through Cross Talk with Wnt Pathway in Xenotransplantation. AB - BACKGROUND: Cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig)-modified bone marrow-derived mesenchymal stem cells (MSCs-CTLA4) have excellent osteogenic function in xenografts, but their mechanism of action remains to be elucidated. As bidirectional signaling between erythropoietin-producing hepatocyte receptors B4 (EphB4) and ephrinB2 is vital for bone remodeling, this study aimed to fully characterize the role of MSCs-CTLA4 in promoting bone regeneration in xenotransplantation through EphB4/ephrinB2 and their cross talk with the Wnt/beta catenin pathway. METHODS: MSCs-CTLA4 were investigated for their osteogenic capacity through xenotransplantation in vivo. MSCs-CTLA4 were treated with ephrinB2-FC or FC under conditions of osteogenic induction and cultured with or without immune activation conditions established by phytohemagglutinin and peripheral blood mononuclear cells in vitro. Osteogenesis markers and the Wnt pathway-related molecules such as EphB4, runt-related transcription factor 2 (Runx2), collagen 1 (COL1), osteocalcin (OCN), alkaline phosphatase (ALP), calcium nodus, beta-catenin, phospho-glycogen synthase kinase 3-beta (p-GSK 3beta)-Ser9, and glycogen synthase kinase 3-beta (GSK-3beta) were detected. RESULTS: MSCs-CTLA4-based xenografts show better osteogenic capacity compared with MSC-based xenografts. EphB4 expression was reduced in MSCs compared with MSCs-CTLA4 under immune activation conditions. In ephrinB2-FC-treated cells, levels of osteogenesis markers were increased compared with FC-treated cells. The activity of GSK-3 was inhibited and the expression of beta-catenin in MSCs was increased by ephrinB2-FC treatment. CONCLUSIONS: CTLA4 modification maintains EphB4 expression in MSCs under immune activation conditions, and EphB4 cross talk with the Wnt pathway promotes osteogenic differentiation of MSCs-CTLA4. PMID- 26132740 TI - Agarose Microchambers for Long-term Calcium Imaging of Caenorhabditis elegans. AB - Behavior is controlled by the nervous system. Calcium imaging is a straightforward method in the transparent nematode Caenorhabditis elegans to measure the activity of neurons during various behaviors. To correlate neural activity with behavior, the animal should not be immobilized but should be able to move. Many behavioral changes occur during long time scales and require recording over many hours of behavior. This also makes it necessary to culture the worms in the presence of food. How can worms be cultured and their neural activity imaged over long time scales? Agarose Microchamber Imaging (AMI) was previously developed to culture and observe small larvae and has now been adapted to study all life stages from early L1 until the adult stage of C. elegans. AMI can be performed on various life stages of C. elegans. Long-term calcium imaging is achieved without immobilizing the animals by using short externally triggered exposures combined with an electron multiplying charge-coupled device (EMCCD) camera recording. Zooming out or scanning can scale up this method to image up to 40 worms in parallel. Thus, a method is described to image behavior and neural activity over long time scales in all life stages of C. elegans. PMID- 26132741 TI - Association Between Progression and Improvement of Acute Kidney Injury and Mortality in Critically Ill Children. AB - OBJECTIVE: To determine whether the progression and/or improvement of acute kidney injury in critically ill children is associated with mortality. DESIGN: Retrospective. SETTING: Multidisciplinary, tertiary care, 24-bed PICU. PATIENTS: A TOTAL OF: 8,260 patients who were 1 month to 21 years old with no chronic kidney disease admitted between May 2003 and March 2012. INTERVENTIONS: We analyzed patients based on their acute kidney injury stage as per the Kidney Disease Improving Global Outcomes acute kidney injury serum creatinine staging criteria on ICU admission, peak (highest acute kidney injury stage reached), and trough (lowest acute kidney injury stage after the peak) during their ICU stay. Nonrenal organ dysfunction was measured with a modified Pediatric Logistic Organ Dysfunction score. The primary outcome was 28-day mortality. p values were based on Yates-corrected chi-square test and logistic regression. MEASUREMENTS AND MAIN RESULTS: Of the 8,260 patients, 529 (6.4%) had acute kidney injury on ICU admission and 974 (11.8%) had acute kidney injury during their ICU course. The 28 day mortality was 2.7% for patients with no acute kidney injury and 25.3% for patients with acute kidney injury. Patients in whom acute kidney injury developed or had worsening acute kidney injury from admission to peak and reached acute kidney injury stage 2 or 3 had higher mortality than those who remained at an acute kidney injury stage 1 (17.3-17.8% vs 32.2-37.9%; p <= 0.003). Patients whose acute kidney injury resolved after the peak had lower mortality than those who retained the same degree of acute kidney injury (9-13.5% vs 37.3-44%; p <= 0.04). Patients with acute kidney injury that resolved still had higher mortality than those who never developed acute kidney injury (11.2% vs 2.7%; p < 0.001). Multivariate regression demonstrated that the association between mortality and acute kidney injury progression was independent of severity of illness at admission and the severity of nonrenal organ dysfunction during the first week of ICU stay (p <= 0.01). CONCLUSION: Progression of acute kidney injury per the Kidney Disease Improving Global Outcomes staging criteria is independently associated with increased mortality in the PICU while its improvement is associated with a stepwise decrease in mortality. PMID- 26132742 TI - Outcomes of Preterm Neonates Transferred Between Tertiary Perinatal Centers. AB - OBJECTIVE: To verify if preterm neonates transferred between tertiary referral centers have worse outcomes than matched untransferred infants. DESIGN: Cohort study with a historically matched control group. SETTING: Two tertiary-level neonatal ICUs. PATIENTS: Seventy-five neonates per group. INTERVENTIONS: Transfer between tertiary-level neonatal ICUs carried out by a fully equipped transportation team. MEASUREMENTS AND MAIN RESULTS: We measured in-hospital mortality, frequency of intraventricular hemorrhage greater than 2nd grade, periventricular leukomalacia, necrotizing enterocolitis greater than or equal to grade 2, bronchopulmonary dysplasia, composite outcomes (in-hospital mortality/bronchopulmonary dysplasia, in-hospital mortality/intraventricular hemorrhage > 2nd grade, and bronchopulmonary dysplasia/periventricular leukomalacia/intraventricular hemorrhage > 2nd grade), length of neonatal ICU stay, weight at discharge, and time spent on ventilatory support. Seventy-five similar (except for antenatal steroids administration) neonates were enrolled in each cohort. Cohorts did not differ in mortality, bronchopulmonary dysplasia, intraventricular hemorrhage greater than 2nd grade, periventricular leukomalacia, necrotizing enterocolitis greater than or equal to grade 2, any composite outcomes, neonatal ICU stay, weight at discharge, and duration of respiratory support. Results were unchanged adjusting for antenatal steroids. CONCLUSIONS: Neonatal transfer between tertiary-level centers does not impact on clinical outcomes, if performed under optimal conditions. PMID- 26132743 TI - Cerebrovascular Pressure Reactivity in Children With Traumatic Brain Injury. AB - OBJECTIVE: Traumatic brain injury is a significant cause of morbidity and mortality in children. Cerebral autoregulation disturbance after traumatic brain injury is associated with worse outcome. Pressure reactivity is a fundamental component of cerebral autoregulation that can be estimated using the pressure reactivity index, a correlation between slow arterial blood pressure, and intracranial pressure fluctuations. Pressure-reactivity index has shown prognostic value in adult traumatic brain injury, with one study confirming this in children. Pressure-reactivity index can identify a cerebral perfusion pressure range within which pressure reactivity is optimal. An increasing difference between optimal cerebral perfusion pressure and cerebral perfusion pressure is associated with worse outcome in adult traumatic brain injury; however, this has not been investigated in children. Our objective was to study pressure-reactivity index and optimal cerebral perfusion pressure in pediatric traumatic brain injury, including associations with outcome, age, and cerebral perfusion pressure. DESIGN: Prospective observational study. SETTING: ICU, Royal Children's Hospital, Melbourne, Australia. PATIENTS: Patients with traumatic brain injury who are 6 months to 16 years old, are admitted to the ICU, and require arterial blood pressure and intracranial pressure monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure, intracranial pressure, and end-tidal CO2 were recorded electronically until ICU discharge or monitoring cessation. Pressure-reactivity index and optimal cerebral perfusion pressure were computed according to previously published methods. Clinical data were collected from electronic medical records. Outcome was assessed 6 months post discharge using the modified Glasgow Outcome Score. Thirty-six patients were monitored, with 30 available for follow-up. Pressure-reactivity index correlated with modified Glasgow Outcome Score (Spearman rho = 0.42; p = 0.023) and was higher in patients with unfavorable outcome (0.23 vs -0.09; p = 0.0009). A plot of pressure reactivity index averaged within 5 mm Hg cerebral perfusion pressure bins showed a U-shape, reaffirming the concept of cerebral perfusion pressure optimization in children. Optimal cerebral perfusion pressure increased with age (rho = 0.40; p = 0.02). Both the duration and magnitude of negative deviations in the difference between cerebral perfusion pressure and optimal cerebral perfusion pressure were associated with unfavorable outcome. CONCLUSIONS: In pediatric patients with traumatic brain injury, pressure-reactivity index has prognostic value and can identify cerebral perfusion pressure targets that may differ from treatment protocols. Our results suggest but do not confirm that cerebral perfusion pressure targeting using pressure-reactivity index as a guide may positively impact on outcome. This question should be addressed by a prospective clinical study. PMID- 26132744 TI - Transhepatic Central Venous Catheters in Pediatric Patients With Congenital Heart Disease. AB - OBJECTIVES: Patients with congenital heart disease may have limited venous access routes as a result of multiple central venous catheters, surgical interventions, and catheterization procedures. Unconventional venous access includes transhepatic central venous catheter. We evaluated transhepatic central venous catheter placed in patients with congenital heart disease and risk factors associated with complications and outcomes. DESIGN: Demographic, procedural, and complication data were retrospectively collected on all patients who underwent transhepatic central venous catheter placement at our center over the past 10 years. SETTING: This study was completed in a tertiary congenital heart center. PATIENTS: A total of 92 transhepatic central venous catheters were placed in 54 patients (63% male patients). The median age and weight of the patient population was 5.7 months and 5.5 kg, respectively. INTERVENTIONS: Placement of a transhepatic central venous catheter. MEASUREMENTS AND MAIN RESULTS: Successful catheter placement occurred in 96% of cases with median procedure time of 54 minutes with a procedural complication rate of 14%. A total of 86 complications occurred in 54 catheters placed during 2,166 catheter-days (39.7 complications per 1,000 catheter-days). Individual complication rates per 1,000 catheter-days included catheter dysfunction (14.8), dislodgement (8.8), systemic infection (5.1), thrombosis (4.2), local infection (3.7), and bleeding (3.2). Two complications contributed to patient deaths. Factors associated with developing complications included polyurethane central venous catheters (p = 0.03) and catheter duration at least 21 days (p = 0.004). The overall mortality in this population was 50% with median length of hospitalization of 49 days (interquartile range, 33-97). CONCLUSIONS: Transhepatic central venous catheters represent a viable option for patients with limited access. Polyurethane catheters and catheter duration at least 21 days are associated with increased transhepatic central venous catheter complications. Although complication rates are higher than more traditional forms of central venous catheters, the long duration of hospitalization and high mortality rates in this patient population attest to their risks for poor outcomes irrespective of venous access. PMID- 26132745 TI - Metabarcoding Analysis of Fungal Diversity in the Phyllosphere and Carposphere of Olive (Olea europaea). AB - The fungal diversity associated with leaves, flowers and fruits of olive (Olea europaea) was investigated in different phenological stages (May, June, October and December) using an implemented metabarcoding approach. It consisted of the 454 pyrosequencing of the fungal ITS2 region and the subsequent phylogenetic analysis of relevant genera along with validated reference sequences. Most sequences were identified up to the species level or were associated with a restricted number of related taxa enabling supported speculations regarding their biological role. Analyses revealed a rich fungal community with 195 different OTUs. Ascomycota was the dominating phyla representing 93.6% of the total number of detected sequences followed by unidentified fungi (3.6%) and Basidiomycota (2.8%). A higher level of diversity was revealed for leaves compared to flowers and fruits. Among plant pathogens the genus Colletotrichum represented by three species (C. godetiae syn. C. clavatum, C. acutatum s.s and C. karstii) was the most abundant on ripe fruits but it was also detected in other organs. Pseudocercospora cladosporioides was detected with a high frequency in all leaf samples and to a less extent in ripe fruits. A much lower relative frequency was revealed for Spilocaea oleagina and for other putative pathogens including Fusarium spp., Neofusicoccum spp., and Alternaria spp. Among non-pathogen taxa, Aureobasidium pullulans, the species complex of Cladosporium cladosporioides and Devriesia spp. were the most represented. This study highlights the existence of a complex fungal consortium including both phytopathogenic and potentially antagonistic microorganisms that can have a significant impact on olive productions. PMID- 26132746 TI - Increasing Protein Distribution Has No Effect on Changes in Lean Mass During a Rugby Preseason. AB - Increasing the frequency of protein consumption is recommended to stimulate muscle hypertrophy with resistance exercise. This study manipulated dietary protein distribution to assess the effect on gains in lean mass during a rugby preseason. Twenty-four developing elite rugby athletes (age 20.1 +/- 1.4 years, mass 101.6 +/- 12.0 kg; M +/- SD) were instructed to consume high biological value (HBV) protein at their main meals and immediately after resistance exercise while limiting protein intake between meals. To manipulate protein intake frequency, the athletes consumed 3 HBV liquid protein supplements (22 g protein) either with main meals (bolus condition) or between meals (frequent condition) for 6 weeks in a 2 * 2 crossover design. Dietary intake and change in lean mass values were compared between conditions by analysis of covariance and correlational analysis. The dietary manipulation successfully altered the protein distribution score (average number of eating occasions containing > 20 g of protein) to 4.0 +/- 0.8 and 5.9 +/- 0.7 (p < .01) for the bolus and frequent conditions, respectively. There was no difference in gains in lean mass between the bolus (1.4 +/- 1.5 kg) and frequent (1.5 +/- 1.4 kg) conditions (p = .91). There was no clear effect of increasing protein distribution from approximately 4 6 eating occasions on changes in lean mass during a rugby preseason. However, other dietary factors may have augmented adaptation. PMID- 26132747 TI - Defect-Engineered Heat Transport in Graphene: A Route to High Efficient Thermal Rectification. AB - Low-dimensional materials such as graphene provide an ideal platform to probe the correlation between thermal transport and lattice defects, which could be engineered at the molecular level. In this work, we perform molecular dynamics simulations and non-contact optothermal Raman measurements to study this correlation. We find that oxygen plasma treatment could reduce the thermal conductivity of graphene significantly even at extremely low defect concentration (~ 83% reduction for ~ 0.1% defects), which could be attributed mainly to the creation of carbonyl pair defects. Other types of defects such as hydroxyl, epoxy groups and nano-holes demonstrate much weaker effects on the reduction where the sp(2) nature of graphene is better preserved. With the capability of selectively functionalizing graphene, we propose an asymmetric junction between graphene and defective graphene with a high thermal rectification ratio of ~ 46%, as demonstrated by our molecular dynamics simulation results. Our findings provide fundamental insights into the physics of thermal transport in defective graphene, and two-dimensional materials in general, which could help on the future design of functional applications such as optothermal and electrothermal devices. PMID- 26132748 TI - Dihalo(imidazolium)sulfuranes: A Versatile Platform for the Synthesis of New Electrophilic Group-Transfer Reagents. AB - The syntheses of imidazolium thiocyanates and imidazolium thioalkynes from dihalo(imidazolium) sulfuranes are reported and their reactivities as CN(+) and R CC(+) synthons evaluated, respectively. The easy and scalable preparation of these electrophilic reagents, their operationally simple handling, broad substrate scope, and functional group tolerance clearly illustrate the potential of these species to become a reference for the direct electrophilic cyanation and alkynylation of organic substrates. PMID- 26132749 TI - Targeted Data-Independent Acquisition and Mining Strategy for Trace Drug Metabolite Identification Using Liquid Chromatography Coupled with Tandem Mass Spectrometry. AB - Detection and identification of unknown or low-level drug-related metabolites in complex biological materials is an ongoing challenge. A highly selective and sensitive method could be a possible solution. Here, we proposed a targeted data independent acquisition and mining (TDIAM) strategy for the rapid identification of trace drug metabolites using ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). In this strategy, raw data is acquired by a novel tm-MS scan, which contains an interleaved full MS scan with a targeted mass range and a product ion scan by selecting all ions in the targeted mass range as precursor ions. For efficient discovery of metabolites, raw data are analyzed by a new postacquisition processing method, Molecule- and Fragmentation-driven Mass Defect Filters (MF MDFs), which was developed based on the fragmentation of parent drug to pick out molecular ions and fragment ions of potential metabolites from the complex matrix. When applying the proposed strategy to paclitaxel metabolism research, we successfully identified 10 metabolites, among which six were not previously reported. The results demonstrated that TDIAM greatly improved throughput, detective sensitivity, and selectivity and, more importantly, yielded almost the same spectrum as traditional HRMS/MS. Therefore, TDIAM provides structure enriched evidence to confirm the existence and elucidate the structures of metabolites. This strategy is suitable for identification of metabolites present at low concentrations in a complex matrix, and it has the potential to provide an efficient, sensitive, and labor-saving solution for drug metabolite research. PMID- 26132750 TI - Stereoselective Alkylation of (S)-N-Acyl-4-isopropyl-1,3-thiazolidine-2-thiones Catalyzed by (Me3P)2NiCl2. AB - The structurally simple (Me3P)2NiCl2 complex catalyzes SN1-type alkylations of chiral N-acyl thiazolidinethiones with diarylmethyl methyl ethers and other stable carbenium cations. The former can contain a variety of functional groups and heteroatoms at the alpha-position. The resultant adducts are isolated as single diastereomers in high yields and can be converted into enantiomerically pure derivatives in a straightforward manner. PMID- 26132752 TI - Structure and stability of noble gas bound EX3+ compounds (E = C, Ge, Sn, Pb; X = H, F, Cl, Br). AB - It has been analyzed at the MP2/def2-QZVPPD level whether EX3+ (E = C-Pb; X = H, F-Br) can bind noble gas atoms. Geometrical and electronic structures, dissociation energy values, thermochemical parameters, natural bond order, electron density, and energy decomposition analyses highlight the possibility of such noble gas bound EX3+ compounds. Except He and Ne, the other heavier congeners of this family make quite strong bonds with E. In fact, the dissociations of Ar-Rn bound analogues turn out to be endergonic in nature at 298 K, except in the cases of ArGe Cl3+, Ar/KrGeBr3+, and ArSnBr3+. GeH3+ and EF3+ (E = Ge-Pb) can even bind two Ng atoms with reasonably high dissociation energy. As the pz orbital of the E center in EX3+ plays a crucial role in its binding with the noble gas atoms, the effect of the pi back-bonding causing X -> E electron transfer ought to be properly understood. Due to the larger back-donation, the Ng binding ability of EX3+ gradually decreases along F to Br. EH2+ and the global minimum HE(+...) H2 (E = Sn, Pb) complexes are also able to bind Ar-Rn atoms quite effectively. The Ng?E bonds in Ar-Rn bound CH3+, GeH3+, and EF3+ (E = Ge Pb) and Xe/Rn?E bonds in NgECl3+ and NgEBr3+ (E = Ge, Sn) are mainly of covalent type. PMID- 26132751 TI - Comorbidities and Quality of Life among Breast Cancer Survivors: A Prospective Study. AB - Many breast cancer survivors have coexistent chronic diseases or comorbidities at the time of their cancer diagnosis. The purpose of the study was to evaluate the association of comorbidities on breast cancer survivors' quality of life. A prospective design was used to recruit 140 women before cancer surgery, 134 women completed the study. Comorbidities were assessed using self-report and verified by medical record review and the Charlson Comorbidity Index (CCI) before and 12 month after cancer surgery. Quality of life was evaluated using Short-Form Health Survey (SF-36 v2). Descriptive statistics, chi-square tests, t-tests, Fisher's exact test, and correlations were performed for data analysis. A total of 28 comorbidities were identified. Among the 134 patients, 73.8% had at least one of the comorbidities, 54.7% had 2-4, and only 7.4% had 5-8. Comorbidities did not change at 12 months after surgery. Numbers of comorbidities by patients' self report and weighted categorization of comorbidities by CCI had a similar negative correlation with overall quality of life scores as well as domains of general health, physical functioning, bodily pain, and vitality. Comorbidities, specifically hypertension, arthritis, and diabetes, were associated with poorer quality of life in multiple domains among breast cancer survivors. Future research should consider the combined influence of comorbidity and cancer on patients' quality of life. PMID- 26132753 TI - Eight Personal Characteristics Associated with the Power to Live with Disasters as Indicated by Survivors of the 2011 Great East Japan Earthquake Disaster. AB - People perceive, judge, and behave differently in disasters and in a wide range of other difficult situations depending on their personal characteristics. The power to live, as captured by characteristics that are advantageous for survival in such situations, has thus far been modeled in arbitrary ways. Conceptualizing such characteristics in more objective ways may be helpful for systematic preparations for future disasters and life difficulties. Here, we attempted to identify the major factors of the power to live by summarizing the opinions of survivors of the 2011 Great East Japan Earthquake disaster. We conducted personal interviews with 78 survivors about their survival experiences and elicited their opinions about the power to live as relevant to those experiences. We then incorporated these opinions into a questionnaire that was completed by 1400 survivors. Factor analysis identified eight factors related to the power to live: leadership, problem solving, altruism, stubbornness, etiquette, emotional regulation, self-transcendence, and active well-being. All factors had sufficient internal construct validity, and six of them showed significant associations with one or more measures of survival success in the disaster, including immediate tsunami evacuation, problem solving in refugee situations, recovery during reconstruction, physical health, and mental health. Overall, the personal characteristics described by the eight factors largely overlap with those described in previous arbitrary models. Further research should investigate the domains, phases, and contexts in which each factor contributes to survival, address whether the factors are rooted in nature or in nurture, and explore their psychological or physiological bases. PMID- 26132755 TI - Natriuretic peptides and cardiovascular variability. PMID- 26132754 TI - Association of Television Viewing Time with Body Composition and Calcified Subclinical Atherosclerosis in Singapore Chinese. AB - OBJECTIVE: Sedentary behavior such as television viewing may be an independent risk factor for coronary heart disease. However, few studies have assessed the impact of television viewing time on coronary artery calcification and it remains unclear how body fat contributes to this relationship. The aim of this study is to evaluate the association between television viewing time and subclinical atherosclerosis and whether effects on visceral or subcutaneous fat may mediate any associations observed. METHODS: This was a cross-sectional study of 398 Chinese participants (192 men and 206 women) from Singapore prospective study. Participants were free from known cardiovascular diseases and underwent interview, health screening, computed tomography scans of coronary arteries and abdomen. Spearman's correlation was used to test the correlation between television viewing time, physical activity, body composition and abdominal fat distribution. The association between television viewing time and subclinical atherosclerosis was assessed by multiple logistic regression analysis. RESULTS: In men, television viewing time was significantly correlated with higher body fat mass index, percent body fat, subcutaneous and visceral fat. These associations were in the same direction, but weaker and not statistically significant in women. Television viewing time (hours/day) was associated with subclinical atherosclerosis in men (odds ratio: 1.41, 95% CI: 1.03-1.93) but no significant association was observed in women (odds ratio: 0.88, 95% CI: 0.59-1.31) after adjusting for potential socio-demographic and lifestyle confounders. Further adjustments for biological factors did not affect these associations. CONCLUSIONS: Television viewing time was associated with greater adiposity and higher subcutaneous and visceral fat in men. TV viewing time was also associated with subclinical atherosclerosis in men and the potential mechanisms underlying this association require further investigation. PMID- 26132756 TI - Sleep apnea and night-time hypertension: a role for the vasopressin system? PMID- 26132757 TI - Home or ambulatory blood pressure monitoring for the diagnosis of hypertension? PMID- 26132758 TI - Does skin microcirculation represent a faithful mirror of uric acid alterations? PMID- 26132759 TI - Nondipping status and impaired nitroglycerin-mediated vasodilation in resistant hypertension: evidence and mechanisms. PMID- 26132760 TI - Long-term chronic baroreflex activation: persistent efficacy in patients with heart failure and reduced ejection fraction. AB - AIMS: Baroreflex activation therapy (BAT) has recently been shown to reduce muscle sympathetic nerve activity and hospitalization rate while improving clinical variables through 6 months of therapy in patients with heart failure and reduced ejection fraction (HFrEF). The objective of the present study is to extend the information on this patient cohort over a long-term follow-up. METHODS AND RESULTS: Eleven patients were enrolled in the study and presented with optimized, stable medical therapy, New York Heart Association Class III HFrEF with left ventricular ejection fraction 40% or less, impaired functional capacity and no active cardiac resynchronization therapy. For the present report, muscle sympathetic nerve activity, baroreflex sensitivity data and hospitalization rate together with standard clinical data were collected at 12 and 21.5 +/- 4.2 months following BAT activation. Two patients died during long-term follow-up. The remaining nine patients maintained the improvements observed at 6 months, including reduced sympathetic activity and rates of hospitalization. CONCLUSION: BAT provides long-term chronic reductions in sympathetic activity and utilization of hospital resources in patients with HFrEF. General clinical presentation, quality of life and functional capacity are likewise improved and maintained. The temporal association of BAT with sympathetic drive diminution and improvement in objective clinical measures suggests a cause-and-effect relationship that will be verified in future randomized controlled trials of outcome. PMID- 26132762 TI - Dietary fiber and blood pressure. PMID- 26132761 TI - A case report of reninoma: radiological and pathological features of the tumour and characterization of tumour-derived juxtaglomerular cells in culture. AB - CASE REPORT: A 20-year-old woman presented with malignant hypertension associated with hypokalemia, metabolic alkalosis and elevated plasma renin and aldosterone levels. Computed tomography angiography (CTA) evidenced a 22 mm tissular mass in the posterior cortex of the left kidney, and 18F-flurodeoxyglucose PET (18-FDG PET) imaging showed no hypermetabolism of the tumour. Following nephron-sparing surgery, blood pressure and potassium levels rapidly normalized, allowing interruption of all treatments within 2 weeks. DISCUSSION: Reninoma is a rare juxtaglomerular cell tumour (JGCT) producing excessive amounts of renin resulting in severe hypertension. Pathological studies revealed that tumoural cells highly expressed renin and contained electron-dense structures, typical of renin containing granules. Tumoural cells also exhibited the vascular cell surface marker CD34, but, in contrast with previous reports, did not express the tyrosine protein kinase Kit (cKit or CD117). Dissociation of the tumour allowed to obtain confluent cultures of elongated smooth muscle actin (SMA)-positive cells producing high amounts of renin. However, after the first passage, subcultured human juxtaglomerular cells rapidly lost renin and CD34 expressions and their ability to produce renin. CONCLUSION: The present case of reninoma emphasizes the need for CTA in the etiologic work up of otherwise unexplained severe hypertension. 18-FDG PET imaging showed no hypermetabolism of the tumour, in accordance with its reported benignity. Pathological studies further emphasized that high expressions of renin and CD34 are typical hallmarks of reninoma. Although CD117 has been proposed to represent a reliable marker of JGCT, the present findings indicate that reninomas may not always express this marker. PMID- 26132763 TI - Ribosomal Protein Mutations Result in Constitutive p53 Protein Degradation through Impairment of the AKT Pathway. AB - Mutations in ribosomal protein (RP) genes can result in the loss of erythrocyte progenitor cells and cause severe anemia. This is seen in patients with Diamond Blackfan anemia (DBA), a pure red cell aplasia and bone marrow failure syndrome that is almost exclusively linked to RP gene haploinsufficiency. While the mechanisms underlying the cytopenia phenotype of patients with these mutations are not completely understood, it is believed that stabilization of the p53 tumor suppressor protein may induce apoptosis in the progenitor cells. In stark contrast, tumor cells from zebrafish with RP gene haploinsufficiency are unable to stabilize p53 even when exposed to acute DNA damage despite transcribing wild type p53 normally. In this work we demonstrate that p53 has a limited role in eliciting the anemia phenotype of zebrafish models of DBA. In fact, we find that RP-deficient embryos exhibit the same normal p53 transcription, absence of p53 protein, and impaired p53 response to DNA damage as RP haploinsufficient tumor cells. Recently we reported that RP mutations suppress activity of the AKT pathway, and we show here that this suppression results in proteasomal degradation of p53. By re-activating the AKT pathway or by inhibiting GSK-3, a downstream modifier that normally represses AKT signaling, we are able to restore the stabilization of p53. Our work indicates that the anemia phenotype of zebrafish models of DBA is dependent on factors other than p53, and may hold clinical significance for both DBA and the increasing number of cancers revealing spontaneous mutations in RP genes. PMID- 26132764 TI - Graph Theoretical Analysis Reveals: Women's Brains Are Better Connected than Men's. AB - Deep graph-theoretic ideas in the context with the graph of the World Wide Web led to the definition of Google's PageRank and the subsequent rise of the most popular search engine to date. Brain graphs, or connectomes, are being widely explored today. We believe that non-trivial graph theoretic concepts, similarly as it happened in the case of the World Wide Web, will lead to discoveries enlightening the structural and also the functional details of the animal and human brains. When scientists examine large networks of tens or hundreds of millions of vertices, only fast algorithms can be applied because of the size constraints. In the case of diffusion MRI-based structural human brain imaging, the effective vertex number of the connectomes, or brain graphs derived from the data is on the scale of several hundred today. That size facilitates applying strict mathematical graph algorithms even for some hard-to-compute (or NP-hard) quantities like vertex cover or balanced minimum cut. In the present work we have examined brain graphs, computed from the data of the Human Connectome Project, recorded from male and female subjects between ages 22 and 35. Significant differences were found between the male and female structural brain graphs: we show that the average female connectome has more edges, is a better expander graph, has larger minimal bisection width, and has more spanning trees than the average male connectome. Since the average female brain weighs less than the brain of males, these properties show that the female brain has better graph theoretical properties, in a sense, than the brain of males. It is known that the female brain has a smaller gray matter/white matter ratio than males, that is, a larger white matter/gray matter ratio than the brain of males; this observation is in line with our findings concerning the number of edges, since the white matter consists of myelinated axons, which, in turn, roughly correspond to the connections in the brain graph. We have also found that the minimum bisection width, normalized with the edge number, is also significantly larger in the right and the left hemispheres in females: therefore, the differing bisection widths are independent from the difference in the number of edges. PMID- 26132765 TI - Technology Use for Problem Solving in Adolescent Type 1 Diabetes. PMID- 26132766 TI - Epidemiological investigation of MERS-CoV spread in a single hospital in South Korea, May to June 2015. AB - In this report, we describe 37 MERS-CoV infection cases (1 primary, 25 secondary, 11 tertiary cases) in a single hospital in South Korea. The median incubation period was six days (95% CI: 4-7 days) and the duration between suspected symptom onset and laboratory confirmation was 6.5 days (95% CI: 4-9). While incubation period was two days longer, the duration from suspected symptom onset to confirmation was shorter in tertiary compared with secondary infections. PMID- 26132767 TI - Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015. AB - South Korea is experiencing the largest outbreak of Middle East respiratory syndrome coronavirus infections outside the Arabian Peninsula, with 166 laboratory-confirmed cases, including 24 deaths up to 19 June 2015. We estimated that the mean incubation period was 6.7 days and the mean serial interval 12.6 days. We found it unlikely that infectiousness precedes symptom onset. Based on currently available data, we predict an overall case fatality risk of 21% (95% credible interval: 14-31). PMID- 26132768 TI - The role of superspreading in Middle East respiratory syndrome coronavirus (MERS CoV) transmission. AB - As at 15 June 2015, a large transmission cluster of Middle East respiratory syndrome coronavirus (MERSCoV)was ongoing in South Korea. To examine the potential for such events, we estimated the level of heterogeneity in MERS-CoV transmission by analyzing data on cluster size distributions. We found substantial potential for superspreading; even though it is likely that R0 < 1 overall, our analysis indicates that cluster sizes of over 150 cases are not unexpected forMERS-CoV infection. PMID- 26132770 TI - Influenza case definitions need to be fit for purpose. PMID- 26132769 TI - Event-based surveillance of food- and waterborne diseases in Europe: urgent inquiries (outbreak alerts) during 2008 to 2013. AB - During 2008 to 2013, 215 outbreak alerts, also known as 'urgent inquiries' (UI), for food- and waterborne diseases were launched in Europe, the majority of them (135; 63%) being related to salmonellosis. For 110 (51%) UI, a potential food vehicle of infection was identified, with vegetables being the most reported category (34;31%). A total of 28% (n = 60) of the outbreaks reported had an international dimension, involving at least two countries (mean: 4; standard deviation: 2; range:2-14). Participating countries posted 2,343 messages(initial posts and replies, excluding updates), with a median of 11 messages per urgent inquiry (range:1-28). Of 60 multicountry UI, 50 involved between two and four countries. The UI allowed early detection of multicountry outbreaks, facilitated the identification of the suspected vehicles and consequently contributed to the timely implementation of control measures. The introduction of an epidemic intelligence information system platform in 2010 has strengthened the role of the Food- and Waterborne Diseases and Zoonoses network in facilitating timely exchange of information between public health authorities of the participating countries. PMID- 26132771 TI - ECDC guidance on prevention of HIV and STIs suggests seven components for inclusion in national EU/EEA public health programmes. PMID- 26132772 TI - Erratum for Euro Surveill. 2014;19(34). PMID- 26132773 TI - Erratum for Euro Surveill. 2015;20(24). PMID- 26132774 TI - Impact of segmentation errors and retinal blood vessels on retinal nerve fibre layer measurements using spectral-domain optical coherence tomography. AB - PURPOSE: To investigate the impact of retinal blood vessels and retinal nerve fibre layer (RNFL) segmentation errors on RNFL measurement. METHODS: One eye of 180 subjects (60 normal, 66 mild-to-moderate and 54 advanced glaucoma subjects) was randomly selected for RNFL imaging with a spectral-domain OCT. The boundaries of the RNFL detected by the instrument software were checked, and the segmentation errors were corrected by a customized computer program. The differences in average and regional RNFL thicknesses (RNFLT) before and after the correction were analysed to determine the frequency of segmentation error (defined as an absolute difference in average RNFLT >5.0 MUm). The ratio of retinal blood vessel cross-sectional area to RNFL cross-sectional area was calculated. RESULTS: The difference in average RNFLT (postsegmentation minus presegmentation refinement) ranged from -3.0 to 2.5 MUm (mean +/- standard deviation: 0.83 +/- 0.86 MUm) in the normal, -2.5 to 5.0 MUm (0.56 +/- 1.08 MUm) in the mild-to-moderate glaucoma and -11.0 to 9.5 MUm (0.05 +/- 3.49 MUm) in the advanced glaucoma groups (p = 0.003). A total of 15% of eyes had average RNFLT measurement error >5.0 MUm in the advanced glaucoma group. The proportion of retinal blood vessels in the RNFL also increased with the severity of glaucoma (p < 0.001) with 4.2 +/- 1.0% in the normal group, 4.9 +/- 1.5% in the mild-to moderate and 8.5 +/- 3.5% in the advanced glaucoma groups. CONCLUSIONS: Inclusion of retinal blood vessels and RNFL segmentation error could adversely affect RNFL measurement, particularly in advanced glaucoma when the RNFL was thin. PMID- 26132775 TI - Molecular Design and Property Prediction for a Series of Novel Dicyclic Cyclotrimethylene Trinitramines (RDX) Derivatized as High Energy Density Materials. AB - Quantum chemistry calculations and thermodynamics methods were carried out to screen out novel high energy density materials (HEDMs) from several new derivatives with dicyclic structures of Cyclotrimethylene trinitramine (RDX). Their volumes, densities, heats of formation, detonation properties and impact sensitivities have been calculated with thermodynamics methods under DFT B3LYP 6 31++g (d, p) level and all of these compounds exhibit good performance as HEDMs. Especially, R4 has given outstanding values as a potential HEDM. Its crystal density (2.07 g/cm(3)), heat of detonation (1.67 kJ/g), detonation velocity (10051m/s), and detonation pressure (48.5 GPa) are even higher than those of CL 20 while its impact sensitivity (h50, 16 cm) remains a relative safety value. The results indicate that the derivative work in common explosives is a good strategy which can design novel HEDMs with high energetic properties and low sensitivity. And furthermore, some mature processes can be used to synthesize them. PMID- 26132777 TI - Increased Plasma S100A12 Levels Are Associated With Diabetic Retinopathy and Prognostic Biomarkers of Macrovascular Events in Type 2 Diabetic Patients. AB - PURPOSE: To explore the association between plasma S100A12 levels and the presence of diabetic retinopathy (DR) and disease outcomes. METHODS: Fasting venous blood samples were collected from 372 subjects (264 relatively healthy subjects with type 2 diabetes and 108 nondiabetic subjects). The plasma CRP, pentosidine, soluble form of the receptor for advanced glycation end products (sRAGE), and S100A12 levels were analyzed in all of the patients and controls. In total, 264 patients with diabetes were followed through office visits and medical records for an average of 17.6 +/- 1.5 months to determine the occurrence of major adverse disease end points. RESULTS: An increase in the plasma levels of S100A12, pentosidine, sRAGE, and hs-CRP from healthy to T2DM to T2DM with DR was observed. Multivariate logistic regression revealed that plasma S100A12 levels were independently associated with the presence of DR in the patients with T2DM (odds ratio, 1.421; 95% confidence interval [CI], 1.036-2.531; P = 0.033). The receiver operating characteristic (ROC) curves for developing DR using the Log S100A12, Log pentosidine, Log sRAGE, and Log hs-CRP values revealed that the area under the receiver operating characteristic curves (AUC) were 0.822 (P < 0.001), 0.561 (P = 0.092), 0.572 (P = 0.051), and 0.566 (P = 0.068), respectively. Increased plasma S100A12 levels might be predictive of future major adverse disease end points in DR patients without a previous diagnosis of macrovascular disease. CONCLUSIONS: The plasma levels of S100A12 are closely associated with the presence of DR and might be a better biomarker for DR and the prediction of future macrovascular events. PMID- 26132776 TI - RefMoB, a Reflectivity Feature Model-Based Automated Method for Measuring Four Outer Retinal Hyperreflective Bands in Optical Coherence Tomography. AB - PURPOSE: To validate a model-driven method (RefMoB) of automatically describing the four outer retinal hyperreflective bands revealed by spectral-domain optical coherence tomography (SDOCT), for comparison with histology of normal macula; to report thickness and position of bands, particularly band 2 (ellipsoid zone [EZ], commonly called IS/OS). METHODS: Foveal and superior perifoveal scans of seven SDOCT volumes of five individuals aged 28 to 69 years with healthy maculas were used (seven eyes for validation, five eyes for measurement). RefMoB determines band thickness and position by a multistage procedure that models reflectivities as a summation of Gaussians. Band thickness and positions were compared with those obtained by manual evaluators for the same scans, and compared with an independent published histological dataset. RESULTS: Agreement among manual evaluators was moderate. Relative to manual evaluation, RefMoB reported reduced thickness and vertical shifts in band positions in a band-specific manner for both simulated and empirical data. In foveal and perifoveal scans, band 1 was thick relative to the anatomical external limiting membrane, band 2 aligned with the outer one-third of the anatomical IS ellipsoid, and band 3 (IZ, interdigitation of retinal pigment epithelium and photoreceptors) was cleanly delineated. CONCLUSIONS: RefMoB is suitable for automatic description of the location and thickness of the four outer retinal hyperreflective bands. Initial results suggest that band 2 aligns with the outer ellipsoid, thus supporting its recent designation as EZ. Automated and objective delineation of band 3 will help investigations of structural biomarkers of dark-adaptation changes in aging. PMID- 26132778 TI - IL-13 Stimulates Proliferation and Expression of Mucin and Immunomodulatory Genes in Cultured Conjunctival Goblet Cells. AB - PURPOSE: To investigate the effects of IL-13 on goblet cell proliferation, differentiation, and expression of mucin and immunomodulatory genes. METHODS: Explants were excised from the conjunctiva of young C57BL/6 mice. Cultures received 200 MUL per week of either Keratinocyte media (KSFM) or KSFM supplemented with 10 ng/mL IL-13 and were incubated for 3 (D3), 7 (D7), or 14 (D14) days. Subsequently, cell proliferation was assessed or cultures were immunostained, collected for dot blot, or for reverse transcription (RT) and quantitative real-time PCR (qPCR) or for RT-PCR gene array. RESULTS: The cultured conjunctival epithelium expressed goblet cell associated keratin 7 and mucins MUC5AC and MUC2 and when stimulated with IL-13 showed increased proliferation at D3 and D7 (P < 0.05) compared with control. MUC5AC expression was increased in the IL-13-treated group at D3 and D14 (P < 0.05). IL-13-treated cultures showed increased chemokine ligand 26 (CCL26), chloride channel calcium activated channel 3 (CLCA3), fas ligand (FasL), and Relm-beta at D7. All conjunctival cultures expressed MUC2, and its expression was decreased at D3 (P < 0.05) and increased at D14 (P < 0.05) with IL-13 treatment. CONCLUSIONS: This study demonstrated that conjunctival goblet cells are IL-13 responsive cells that produce factors known to maintain epithelial barrier, stimulate mucin production, and modulate immune response in nonocular mucosa when treated with IL-13. The functional significance of IL-13-stimulated factors remains to be determined. PMID- 26132779 TI - Aldose Reductase Mediates Transforming Growth Factor beta2 (TGF-beta2)-Induced Migration and Epithelial-To-Mesenchymal Transition of Lens-Derived Epithelial Cells. AB - PURPOSE: Cataract surgery involves removal of lens tissue, but is associated with a high complication rate due to regrowth of residual lens epithelial cells to produce posterior capsule opacification (PCO) and diminished visual acuity. As inhibitors of aldose reductase (AR) have been shown to suppress markers of PCO, our studies were designed to identify a role for AR in the pathogenesis of PCO. METHODS: Sorbinil-mediated AR inhibition was determined by measuring sorbitol accumulation. Cell migration was measured using both transwell and scratch assays. Proteins in the SMAD signaling pathway were measured by Western blotting. The interactions of AR and SMADs were demonstrated by co-immunoprecipitation (Co IP) and proximity ligation assay (PLA). Epithelial-to-mesenchymal transition (EMT) expression was measured by Western blot and quantitative PCR (q-PCR). Matrix metalloproteinase (MMP)-2 and MMP-9 activities were measured in conditioned medium by zymography. RESULTS: We observed that either Sorbinil mediated AR inhibition or siRNA-mediated AR gene knockdown prevented migration of lens epithelial cells following exposure to TGF-beta2. AR inhibition or AR knockdown reduced SMAD and MMP activation triggered by TGF-beta2. In addition, we demonstrated AR inhibition or AR knockdown decreased TGF-beta2-induced expression of EMT markers. Co-IP studies and PLA were used to demonstrate that AR and SMAD2 interact either directly or in close concert with additional factor(s) in a nonenzymatic manner. CONCLUSIONS: This study demonstrates that AR participates in the response of lens epithelial cells to TGF-beta2. Our studies raise the possibility that AR inhibition may be effective in preventing development of PCO by disrupting the TGF-beta2/SMAD pathway. PMID- 26132780 TI - The Effects of Increasing Ocular Surface Stimulation on Blinking and Tear Secretion. AB - PURPOSE: To investigate the effect of varying levels of ocular surface stimulation on the timing and amplitude of the blink and tear secretion. METHODS: Following instillation of fluorescein dye, increasing levels of air flow were directed toward the central corneas of 10 healthy subjects. Interblink interval (IBI), tear meniscus height (TMH), and fluorescence intensity were measured simultaneously. Because blinking can obscure changes in TMH, we developed novel measures of tear secretion by calculating tear meniscus fluorescein concentration (TMFC) from intensity using a mathematical model. The change of TMH and TMFC over trials and the slope of the TMFC within each IBI (IBI-TTR) were further calculated. RESULTS: The mean IBI was decreased by 8.08 +/- 8.54 seconds from baseline to maximum air stimulation. The TMH increase was highly variable (0.41 +/- 0.39 mm) among subjects, compared to the fluorescence tear turnover metrics: decrease in TMFC of 2.84 +/- 0.98 natural logarithm or ln(%) and IBI-TTR of 0.065 +/- 0.032 ln(%)/sec. Ocular surface stimulation was highly correlated with the TMFC and IBI-TTR, but less so with TMH (Pearson's r = 0.71, 0.69, and 0.40, P < 0.01, respectively). Blinking and tearing were significantly correlated with each other (Pearson's r = 0.56, P < 0.01), but tearing lagged behind by an average of 6.54 +/- 4.07 seconds. CONCLUSIONS: Blinking and tearing share a common origin with sensory stimulation at the ocular surface. Both showed a dose-response increase with surface stimulation and were correlated with each other. These methods can potentially be used to understand alterations in ocular surface sensory function and associated protective responses in dry eye and other disorders of the ocular surface. PMID- 26132783 TI - Interfacing Lab-on-a-Chip Embryo Technology with High-Definition Imaging Cytometry. AB - To spearhead deployment of zebrafish embryo biotests in large-scale drug discovery studies, automated platforms are needed to integrate embryo in-test positioning and immobilization (suitable for high-content imaging) with fluidic modules for continuous drug and medium delivery under microperfusion to developing embryos. In this work, we present an innovative design of a high throughput three-dimensional (3D) microfluidic chip-based device for automated immobilization and culture and time-lapse imaging of developing zebrafish embryos under continuous microperfusion. The 3D Lab-on-a-Chip array was fabricated in poly(methyl methacrylate) (PMMA) transparent thermoplastic using infrared laser micromachining, while the off-chip interfaces were fabricated using additive manufacturing processes (fused deposition modelling and stereolithography). The system's design facilitated rapid loading and immobilization of a large number of embryos in predefined clusters of traps during continuous microperfusion of drugs/toxins. It was conceptually designed to seamlessly interface with both upright and inverted fluorescent imaging systems and also to directly interface with conventional microtiter plate readers that accept 96-well plates. Compared with the conventional Petri dish assays, the chip-based bioassay was much more convenient and efficient as only small amounts of drug solutions were required for the whole perfusion system running continuously over 72 h. Embryos were spatially separated in the traps that assisted tracing single embryos, preventing interembryo contamination and improving imaging accessibility. PMID- 26132781 TI - The Relationship Between Serum 25-Hydroxyvitamin D Levels and Nuclear Cataract in the Carotenoid Age-Related Eye Study (CAREDS), an Ancillary Study of the Women's Health Initiative. AB - PURPOSE: To investigate the relationship between serum 25-hydroxyvitamin D (25[OH]D) levels and nuclear cataract among participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI) Observational Study (OS). METHODS: Nuclear cataract was assessed from slit lamp photographs (2001-2004) taken 6 years after collecting serum analyzed for 25(OH)D levels at WHI baseline (1994-1998) in 1278 CAREDS participants age 50 to 79 years. Multivariate (age, iris color, smoking, pulse pressure) odds ratios (ORs) for nuclear cataract (nuclear opacities > level 4 or cataract extraction) by quintiles of serum 25(OH)D were estimated using logistic regression. RESULTS: No significant association was observed between serum 25(OH)D and nuclear cataract among women of all ages (age-adjusted OR [95% confidence interval (CI)] 0.97 [0.65-1.45]). However, there was a significant age interaction (P for interaction = 0.04). There were no significant associations in the women 70 years or older. In women younger than 70 years, we observed an inverse association between serum 25(OH)D and nuclear cataract (multivariate adjusted ORs [95% CI] 0.54 [0.29-0.99] and 0.66 [0.36-1.20] for quintiles 4 and 5 vs. 1, respectively; P = 0.03). Further adjustment for 25(OH)D determinants (body mass index, vitamin D intake, and UVB exposure) attenuated this association. CONCLUSIONS: Serum 25(OH)D levels were unrelated to nuclear opacities in this study sample. However, exploratory analyses suggest a protective association in women younger than 70 years. Further investigations of the relationship between vitamin D and nuclear lens opacities are warranted. PMID- 26132784 TI - Parylene-coated ionic liquid-carbon nanotube actuators for user-safe haptic devices. AB - Simple fabrication, high power-to-weight and power-to-volume ratios, and the ability to operate in open air at low voltage make the ionic electroactive polymer actuators highly attractive for haptic applications. Whenever a direct tactile stimulation of the skin is involved, electrical and chemical insulation as well as a long-term stability of the actuator are required. Because of its inherent physicochemical properties such as high dielectric strength, resistance to solvents, and biological inactivity, Parylene C meets the requirements for making biocompatible actuators. We have studied the displacement and the generated force of Parylene-coated carbon nanotube actuators as well as the encapsulation quality. A 2 MUm coating creates an effective electrical insulation of the actuators without altering the blocking force at frequencies from 50 mHz to 1 Hz. Moreover, the generated strain is preserved at higher frequencies (from 0.5 to 5 Hz). We employed a simple mechanical model to explain the relation between the key parameters-flexural stiffness, displacement, and force-for uncoated and coated actuators. In addition, we demonstrated that our Parylene coated actuators are not damaged by rinsing in liquid media such as 2-propanol or water. In conclusion, our results indicate that Parylene C encapsulated actuators are safe to touch and can be used in contact with human skin and in biomedical applications in direct contact with tissues and physiological fluids. PMID- 26132782 TI - Seeking signatures of reinforcement at the genetic level: a hitchhiking mapping and candidate gene approach in the house mouse. AB - Reinforcement is the process by which prezygotic isolation is strengthened as a response to selection against hybridization. Most empirical support for reinforcement comes from the observation of its possible phenotypic signature: an accentuated degree of prezygotic isolation in the hybrid zone as compared to allopatry. Here, we implemented a novel approach to this question by seeking for the signature of reinforcement at the genetic level. In the house mouse, selection against hybrids and enhanced olfactory-based assortative mate preferences are observed in a hybrid zone between the two European subspecies Mus musculus musculus and M. m. domesticus, suggesting a possible recent reinforcement event. To test for the genetic signature of reinforcing selection and identify genes involved in sexual isolation, we adopted a hitchhiking mapping approach targeting genomic regions containing candidate genes for assortative mating in mice. We densely scanned these genomic regions in hybrid zone and allopatric samples using a large number of fast evolving microsatellite loci that allow the detection of recent selection events. We found a handful of loci showing the expected pattern of significant reduction in variability in populations close to the hybrid zone, showing assortative odour preference in mate choice experiments as compared to populations further away and displaying no such preference. These loci lie close to genes that we pinpoint as testable candidates for further investigation. PMID- 26132785 TI - Isolation and Characterization of Neutrophils with Anti-Tumor Properties. AB - Neutrophils, the most abundant of all white blood cells in the human circulation, play an important role in the host defense against invading microorganisms. In addition, neutrophils play a central role in the immune surveillance of tumor cells. They have the ability to recognize tumor cells and induce tumor cell death either through a cell contact-dependent mechanism involving hydrogen peroxide or through antibody-dependent cell-mediated cytotoxicity (ADCC). Neutrophils with anti-tumor activity can be isolated from peripheral blood of cancer patients and of tumor-bearing mice. These neutrophils are termed tumor-entrained neutrophils (TEN) to distinguish them from neutrophils of healthy subjects or naive mice that show no significant tumor cytotoxic activity. Compared with other white blood cells, neutrophils show different buoyancy making it feasible to obtain a > 98% pure neutrophil population when subjected to a density gradient. However, in addition to the normal high-density neutrophil population (HDN), in cancer patients, in tumor-bearing mice, as well as under chronic inflammatory conditions, distinct low-density neutrophil populations (LDN) appear in the circulation. LDN co-purify with the mononuclear fraction and can be separated from mononuclear cells using either positive or negative selection strategies. Once the purity of the isolated neutrophils is determined by flow cytometry, they can be used for in vitro and in vivo functional assays. We describe techniques for monitoring the anti-tumor activity of neutrophils, their ability to migrate and to produce reactive oxygen species, as well as monitoring their phagocytic capacity ex vivo. We further describe techniques to label the neutrophils for in vivo tracking, and to determine their anti-metastatic capacity in vivo. All these techniques are essential for understanding how to obtain and characterize neutrophils with anti-tumor function. PMID- 26132787 TI - Correction: The Effects of Threonine Phosphorylation on the Stability and Dynamics of the Central Molecular Switch Region of 18.5-kDa Myelin Basic Protein. PMID- 26132786 TI - Improved electrochemical performance of nitrogen doped TiO2-B nanowires as anode materials for Li-ion batteries. AB - N-doped TiO2-B nanowires are prepared by the solvothermal method using TiN nanoparticles as the starting material. X-ray photoelectron spectroscopy shows that the N dopants preferentially occupy the interstitial sites of TiO2-B up to a content of ~0.55 at%. Above this critical value, the N dopants will substitute the oxygen atoms which improve the electronic conductivity of TiO2-B. The maximum proportion of substituted-N in the TiO2-B nanowires is ~1.3 at%. Raman scattering shows that the substituted-N strengthens the Ti(1)-O1-Ti(2) and O1-Ti(1)-O3 bonds of TiO2-B. This improves the stability of the corresponding local structures, thus reducing the distortion of the Li(+) diffusion channel along the b-axis of TiO2-B. As a result, the substituted-N has more of an impact on the electrochemical properties of TiO2-B than the interstitial-N does. The TiO2-B nanowires containing substituted-N dopants exhibit a remarkably enhanced electrochemical performance compared to pure TiO2-B. They show a discharge capacity of 153 mA h g(-1) at the 20 C rate with a capacity retention of 76% after 1000 cycles. In addition, they can deliver a discharge capacity of 100 mA h g(-1) at an ultra-high rate of 100 C, indicating their great potential in high power lithium ion batteries. PMID- 26132788 TI - Competitive Effects of Calcium and Magnesium Ions on the Photochemical Transformation and Associated Cellular Uptake of Iron by the Freshwater Cyanobacterial Phytoplankton Microcystis aeruginosa. AB - Photochemical reduction of iron and iron uptake by Microcystis were investigated in a freshwater medium (pH 8) containing a range of calcium (Ca) and magnesium (Mg) ion concentrations (0.002-20 mM). In a medium containing the chelator ethylenediaminetetraacetic acid (EDTA), 50-fold increases in net photochemical formation rates of unchelated ferrous iron (Fe(II)') were observed as the concentration of calcium or magnesium metal (Me) was increased to exceed the concentration of EDTA. Kinetic modeling of iron transformation processes indicated that the facilitated Fe(II)' formation is attributed to Me-promoted photoreductive dissociation of the ferric iron-EDTA complex. In the medium containing Suwanee River fulvic acid, in contrast, the competitive effect of Me on photochemical Fe(II)' formation appears to be negligible due to the weak binding affinities of fulvic acid to Me. The cellular iron uptake rate in the EDTA-buffered system increased by ~3-fold in the excess Me condition where the increased rate of photochemical Fe(II)' formation was observed, whereas the presence of Me resulted in a decrease in iron uptake rate in the fulvic acid system (by up to 5-fold). The decrease in iron uptake is likely caused by Me binding to iron transporters and other entities involved in intracellular iron transport. The findings of this study indicate a significant effect of Ca and Mg concentrations in natural waters on iron uptake by Microcystis, with the magnitude of effect depending strongly on ligand type. PMID- 26132789 TI - Dual-Modality Noninvasive Mapping of Sentinel Lymph Node by Photoacoustic and Near-Infrared Fluorescent Imaging Using Dye-Loaded Mesoporous Silica Nanoparticles. AB - The imaging of sentinel lymph nodes (SLNs), the first defense against primary tumor metastasis, has been considered as an important strategy for noninvasive tracking tumor metastasis in clinics. In this study, we developed an imaging contrast system based on fluorescent dye-loaded mesoporous silica nanoparticles (MSNPs) that integrate near-infrared (NIR) fluorescent and photoacoustic (PA) imaging modalities for efficient SLN mapping. By balancing the ratio of dye and nanoparticles for simultaneous optimization of dual-modality imaging (NIR and PA), the dye encapsulated MSNP platform was set up to generate both a moderate NIR emission and PA signals simultaneously. Moreover, the underlying mechanisms of the relevance between optical and PA properties were discovered. Subsequently, dual-modality imaging was achieved to visualize tumor draining SLNs up to 2 weeks in a 4T1 tumor metastatic model. Obvious differences in uptake rate and contrast between metastatic and normal SLNs were observed both in vivo and ex vivo. Based on all these imaging data, it was demonstrated that the dye-loaded MSNPs allow detection of regional lymph nodes in vivo with time-domain NIR fluorescent and PA imaging methods efficiently. PMID- 26132802 TI - Should We Reject Donated Organs on Moral Grounds or Permit Allocation Using Non Medical Criteria?: A Qualitative Study. AB - Conditional and directed deceased organ donations occur when donors (or often their next of kin) attempt to influence the allocation of their donated organs. This can include asking that the organs are given to or withheld from certain types of people, or that they are given to specified individuals. Donations of these types have raised ethical concerns, and have been prohibited in many countries, including the UK. In this article we report the findings from a qualitative study involving interviews with potential donors (n = 20), potential recipients (n = 9) and transplant staff (n = 11), and use these results as a springboard for further ethical commentary. We argue that although participants favoured unconditional donation, this preference was grounded in a false distinction between 'medical' and 'non-medical' allocation criteria. Although there are good reasons to maintain organ allocation based primarily upon the existing 'medical' criteria, it may be premature to reject all other potential criteria as being unacceptable. Part of participants' justification for allocating organs using 'medical' criteria was to make the best use of available organs and avoid wasting their potential benefit, but this can also justify accepting conditional donations in some circumstances. We draw a distinction between two types of waste - absolute and relative - and argue that accepting conditional donations may offer a balance between these forms of waste. PMID- 26132803 TI - Effect of Early Rehabilitation during Intensive Care Unit Stay on Functional Status: Systematic Review and Meta-Analysis. AB - BACKGROUND AND AIM: Critically ill survivors may have functional impairments even five years after hospital discharge. To date there are four systematic reviews suggesting a beneficial impact for mobilisation in mechanically ventilated and intensive care unit (ICU) patients, however there is limited information about the influence of timing, frequency and duration of sessions. Earlier mobilisation during ICU stay may lead to greater benefits. This study aims to determine the effect of early rehabilitation for functional status in ICU/high-dependency unit (HDU) patients. DESIGN: Systematic review and meta-analysis. MEDLINE, EMBASE, CINALH, PEDro, Cochrane Library, AMED, ISI web of science, Scielo, LILACS and several clinical trial registries were searched for randomised and non-randomised clinical trials of rehabilitation compared to usual care in adult patients admitted to an ICU/HDU. Results were screened by two independent reviewers. Primary outcome was functional status. Secondary outcomes were walking ability, muscle strength, quality of life, and healthcare utilisation. Data extraction and methodological quality assessment using the PEDro scale was performed by primary reviewer and checked by two other reviewers. The authors of relevant studies were contacted to obtain missing data. RESULTS: 5733 records were screened. Seven articles were included in the narrative synthesis and six in the meta-analysis. Early rehabilitation had no significant effect on functional status, muscle strength, quality of life, or healthcare utilisation. However, early rehabilitation led to significantly more patients walking without assistance at hospital discharge (risk ratio 1.42; 95% CI 1.17-1.72). There was a non significant effect favouring intervention for walking distance and incidence of ICU-acquired weakness. CONCLUSIONS: Early rehabilitation during ICU stay was not associated with improvements in functional status, muscle strength, quality of life or healthcare utilisation outcomes, although it seems to improve walking ability compared to usual care. Results from ongoing studies may provide more data on the potential benefits of early rehabilitation in critically ill patients. PMID- 26132804 TI - Conundrum of Sexual Decision Making in Marital Relationships: Safer-Sex Knowledge, Behavior, and Attitudes of Married Women in Zambia. AB - Recent research suggests that Zambian women face an increasing risk of contracting human immunodeficiency virus (HIV) within marital relationships. Married women's perceived ability to negotiate safer sex or adopt self-efficacy practices is recognized as critical in preventing new infections within marriage. Yet women's self-efficacy practices, such as requesting condom use or refusing sex within marriage, are influenced by individual and context-specific factors. Using the 2007 Zambia Demographic and Health Survey data from 4,306 married women, this article examines the association between married women's perceived ability to negotiate safer sex and a range of attitudinal, knowledge, and sociodemographic variables. Results from complementary log-log regression models reveal that married women who have factual knowledge about HIV transmission and prevention, as well as those who have been tested for their HIV serostatus, were more likely to report they can request that their husbands use a condom. Rural married women were more likely to report they can refuse their husbands sex compared to woman in urban areas. Likewise, married women who agree that a wife is justified in refusing her husband sex if he sleeps with other women were more likely to report they can negotiate safer sex compared to women who disagree. These findings suggest that married women are able to negotiate safer sex if they have correct factual knowledge about HIV transmission and are aware of their rights within marital relations. PMID- 26132790 TI - Regulation of Transcript Elongation. AB - Bacteria lack subcellular compartments and harbor a single RNA polymerase that synthesizes both structural and protein-coding RNAs, which are cotranscriptionally processed by distinct pathways. Nascent rRNAs fold into elaborate secondary structures and associate with ribosomal proteins, whereas nascent mRNAs are translated by ribosomes. During elongation, nucleic acid signals and regulatory proteins modulate concurrent RNA-processing events, instruct RNA polymerase where to pause and terminate transcription, or act as roadblocks to the moving enzyme. Communications among complexes that carry out transcription, translation, repair, and other cellular processes ensure timely execution of the gene expression program and survival under conditions of stress. This network is maintained by auxiliary proteins that act as bridges between RNA polymerase, ribosome, and repair enzymes, blurring boundaries between separate information-processing steps and making assignments of unique regulatory functions meaningless. Understanding the regulation of transcript elongation thus requires genome-wide approaches, which confirm known and reveal new regulatory connections. PMID- 26132805 TI - FT overexpression induces precocious flowering and normal reproductive development in Eucalyptus. AB - Eucalyptus trees are among the most important species for industrial forestry worldwide. However, as with most forest trees, flowering does not begin for one to several years after planting which can limit the rate of conventional and molecular breeding. To speed flowering, we transformed a Eucalyptus grandis * urophylla hybrid (SP7) with a variety of constructs that enable overexpression of FLOWERING LOCUS T (FT). We found that FT expression led to very early flowering, with events showing floral buds within 1-5 months of transplanting to the glasshouse. The most rapid flowering was observed when the cauliflower mosaic virus 35S promoter was used to drive the Arabidopsis thaliana FT gene (AtFT). Early flowering was also observed with AtFT overexpression from a 409S ubiquitin promoter and under heat induction conditions with Populus trichocarpa FT1 (PtFT1) under control of a heat-shock promoter. Early flowering trees grew robustly, but exhibited a highly branched phenotype compared to the strong apical dominance of nonflowering transgenic and control trees. AtFT-induced flowers were morphologically normal and produced viable pollen grains and viable self- and cross-pollinated seeds. Many self-seedlings inherited AtFT and flowered early. FT overexpression-induced flowering in Eucalyptus may be a valuable means for accelerating breeding and genetic studies as the transgene can be easily segregated away in progeny, restoring normal growth and form. PMID- 26132806 TI - Improved Confidence Intervals for the Youden Index. AB - The Youden Index is a summary measurement of the receiver operating characteristic (ROC) curve for the accuracy of a diagnostic test with ordinal or continuous endpoints. The bootstrap confidence interval based on the adjusted proportion estimate was shown to have satisfactory performance among the existing confidence intervals, including the parametric interval via the delta method. In this article, we propose two confidence intervals using the square-and-add limits based on the Wilson score method. We compare the two proposed intervals with the existing interval with extensive simulation studies. The new interval based on the empirical proportion estimate generally has better performance than that based on the adjusted proportion estimate. A real example from a clinical trial of prostate cancer is illustrated for the application of the new intervals. PMID- 26132807 TI - Information Seeking in Uncertainty Management Theory: Exposure to Information About Medical Uncertainty and Information-Processing Orientation as Predictors of Uncertainty Management Success. AB - Uncertainty management theory outlines the processes through which individuals cope with health-related uncertainty. Information seeking has been frequently documented as an important uncertainty management strategy. The reported study investigates exposure to specific types of medical information during a search, and one's information-processing orientation as predictors of successful uncertainty management (i.e., a reduction in the discrepancy between the level of uncertainty one feels and the level one desires). A lab study was conducted in which participants were primed to feel more or less certain about skin cancer and then were allowed to search the World Wide Web for skin cancer information. Participants' search behavior was recorded and content analyzed. The results indicate that exposure to two health communication constructs that pervade medical forms of uncertainty (i.e., severity and susceptibility) and information processing orientation predicted uncertainty management success. PMID- 26132808 TI - WHO European Childhood Obesity Surveillance Initiative: health-risk behaviours on nutrition and physical activity in 6-9-year-old schoolchildren. AB - OBJECTIVE: To assess to what extent eight behavioural health risks related to breakfast and food consumption and five behavioural health risks related to physical activity, screen time and sleep duration are present among schoolchildren, and to examine whether health-risk behaviours are associated with obesity. DESIGN: Cross-sectional design as part of the WHO European Childhood Obesity Surveillance Initiative (school year 2007/2008). Children's behavioural data were reported by their parents and children's weight and height measured by trained fieldworkers. Descriptive statistics and logistic regression analyses were performed. SETTING: Primary schools in Bulgaria, Lithuania, Portugal and Sweden; paediatric clinics in the Czech Republic. SUBJECTS: Nationally representative samples of 6-9-year-olds (n 15 643). RESULTS: All thirteen risk behaviours differed statistically significantly across countries. Highest prevalence estimates of risk behaviours were observed in Bulgaria and lowest in Sweden. Not having breakfast daily and spending screen time >=2 h/d were clearly positively associated with obesity. The same was true for eating 'foods like pizza, French fries, hamburgers, sausages or meat pies' >3 d/week and playing outside <1 h/d. Surprisingly, other individual unhealthy eating or less favourable physical activity behaviours showed either no or significant negative associations with obesity. A combination of multiple less favourable physical activity behaviours showed positive associations with obesity, whereas multiple unhealthy eating behaviours combined did not lead to higher odds of obesity. CONCLUSIONS: Despite a categorization based on international health recommendations, individual associations of the thirteen health-risk behaviours with obesity were not consistent, whereas presence of multiple physical activity related risk behaviours was clearly associated with higher odds of obesity. PMID- 26132810 TI - Effects of reduced water quality on coral reefs in and out of no-take marine reserves. AB - Near-shore marine environments are increasingly subjected to reduced water quality, and their ability to withstand it is critical to their persistence. The potential role marine reserves may play in mitigating the effects of reduced water quality has received little attention. We investigated the spatial and temporal variability in live coral and macro-algal cover and water quality during moderate and major flooding events of the Fitzroy River within the Keppel Bay region of the Great Barrier Reef Marine Park from 2007 to 2013. We used 7 years of remote sensing data on water quality and data from long-term monitoring of coral reefs to quantify exposure of coral reefs to flood plumes. We used a distance linear model to partition the contribution of abiotic and biotic factors, including zoning, as drivers of the observed changes in coral and macro algae cover. Moderate flood plumes from 2007 to 2009 did not affect coral cover on reefs in the Keppel Islands, suggesting the reef has intrinsic resistance against short-term exposure to reduced water quality. However, from 2009 to 2013, live coral cover declined by ~ 50% following several weeks of exposure to turbid, low salinity water from major flood plume events in 2011 and subsequent moderate events in 2012 and 2013. Although the flooding events in 2012 and 2013 were smaller than the flooding events between 2007 to 2009, the ability of the reefs to withstand these moderate floods was lost, as evidenced by a ~ 20% decline in coral cover between 2011 to 2013. Although zoning (no-take reserve or fished) was identified a significant driver of coral cover, we recorded consistently lower coral cover on reserve reefs than on fished reefs throughout the study period and significantly lower cover in 2011. Our findings suggest that even reefs with an inherent resistance to reduced water quality are not able to withstand repeated disturbance events. The limitations of reserves in mitigating the effects of reduced water quality on near-shore coral reefs underscores the importance of integrated management approaches that combine effective land-based management with networks of no-take reserves. PMID- 26132809 TI - Anti-citrullinated-protein-antibody-specific intravenous immunoglobulin attenuates collagen-induced arthritis in mice. AB - Administration of intravenous immunoglobulin (IVIg) is a recognized safe and efficient immunomodulation therapy for many autoimmune diseases. Anti-idiotypic antibody binding to pathogenic autoantibodies was proposed as one of the mechanisms attributed to the protective activity of IVIg in autoimmunity. The aim of this study was to fractionate the anti-anti-citrullinated protein anti idiotypic-antibodies (anti-ACPA) from an IVIg preparation and to test it as a treatment for collagen-induced arthritis in mice. IVIg was loaded onto an ACPA column. The eluted fraction was defined as ACPA-specific-IVIg (ACPA-sIVIg). Collagen-induced-arthritis (CIA) was induced in mice. Mice were treated weekly with ACPA-sIVIg, low-dose-IVIg, high-dose-IVIg and phosphate-buffered saline (PBS). Sera-ACPA titres, anti-collagen anitbodies and cytokine levels were analysed by enzyme-linked immunosorbent assay (ELISA); antibody-forming-cell activity by enzyme-linked imunospot (ELISPOT) assay; and expansion of regulatory T cell (Treg ) population by fluorescence activated cell sorter (FACS). ACPA sIVIg inhibited ACPA binding to citrullinated-peptides (CCP) in vitro 100 times more efficiently than the IVIg compound. ACPA-sIVIg was significantly more effective than the IVIg-preparation in attenuating the development of collagen induced arthritis. Splenocytes from CIA mice treated with ACPA-sIVIg reduced the ACPA and anti-collagen-antibody titres, including the number of anti-collagen and ACPA antibody-forming cells. In parallel, splenocytes from ACPA-sIVIg treated mice secreted higher levels of anti-inflammatory cytokines and lower proinflammatory cytokines. The ACPA-sIVIg inhibitory potential was accompanied with expansion of the Treg population. Low-dose IVIg did not affect the humoral and cellular response in the CIA mice in comparison to the PBS-treated mice. Based on our results, IVIg may be considered as a safe compound for treating patients with rheumatoid arthritis by neutralizing pathogenic autoantibodies, reducing proinflammatory cytokines and expanding the Treg population. PMID- 26132811 TI - Gpr97 Is Dispensable for Inflammation in OVA-Induced Asthmatic Mice. AB - BACKGROUND: Asthma is a complex inflammatory disorder involving the activation and invasion of various immune cells. GPR97 is highly expressed in some immunocytes, including mast cells and eosinophils, which play critical roles in asthma development. However, the role of Gpr97 in regulating airway inflammation in asthma has rarely been reported. In this study, we investigated the potential role of Gpr97 in the development of allergic asthma in mice. METHODS: Relevant airway asthmatic mouse models were constructed with both wild-type and Gpr97-/- mice sensitized to 250 MUg ovalbumin (OVA). The levels of interleukin IL-4, IL-6 and IFN-gamma, which are involved in OVA-induced asthma, in the bronchoalveolar lavage fluid (BALF) and the IgE level in the serum were examined by enzyme-linked immunosorbent assay (ELISA). The invasion of mast cells and eosinophils into lung tissues was assessed by immunohistochemical and eosinophil peroxidase activity assays, respectively. Goblet cell hyperplasia and mucus production were morphologically evaluated with periodic acid-Schiff (PAS) staining. RESULTS: In our study, no obvious alteration in the inflammatory response or airway remodeling was found in the Gpr97-deficient mice with OVA-induced asthma. Neither the secretion of cytokines, including IL-4, IL-6 and IFN-gamma, nor inflammatory cell recruitment was altered in the Gpr97-deficient mice. Moreover, Gpr97 deficiency did not affect airway remodeling or mucus production in the asthma mouse model. CONCLUSION: Our findings imply that Gpr97 might not be required for the development of airway inflammation in OVA-induced allergic asthma in mice. PMID- 26132812 TI - Design and Construction of Artificial Extracellular Matrix (aECM) Proteins from Escherichia coli for Skin Tissue Engineering. AB - Recombinant technology is a versatile platform to create novel artificial proteins with tunable properties. For the last decade, many artificial proteins that have incorporated functional domains derived from nature (or created de novo) have been reported. In particular, artificial extracellular matrix (aECM) proteins have been developed; these aECM proteins consist of biological domains taken from fibronectin, laminins and collagens and are combined with structural domains including elastin-like repeats, silk and collagen repeats. To date, aECM proteins have been widely investigated for applications in tissue engineering and wound repair. Recently, Tjin and coworkers developed integrin-specific aECM proteins designed for promoting human skin keratinocyte attachment and propagation. In their work, the aECM proteins incorporate cell binding domains taken from fibronectin, laminin-5 and collagen IV, as well as flanking elastin like repeats. They demonstrated that the aECM proteins developed in their work were promising candidates for use as substrates in artificial skin. Here, we outline the design and construction of such aECM proteins as well as their purification process using the thermo-responsive characteristics of elastin. PMID- 26132813 TI - A Hydrogel Construct and Fibrin-based Glue Approach to Deliver Therapeutics in a Murine Myocardial Infarction Model. AB - The murine MI model is widely recognized in the field of cardiovascular disease, and has consistently been used as a first step to test the efficacy of treatments in vivo. The traditional, established protocol has been further fine-tuned to minimize the damage to the animal. Notably, the pectoral muscle layers are teased away rather than simply cut, and the thoracotomy is approached intercostally as opposed to breaking the ribs in a sternotomy, preserving the integrity of the ribcage. With these changes, the overall stress on the animal is decreased. Stem cell therapies aimed to alleviate the damage caused by MIs have shown promise over the years for their pro-angiogenic and anti-apoptotic benefits. Current approaches of delivering cells to the heart surface typically involve the injection of the cells either near the damaged site, within a coronary artery, or into the peripheral blood stream. While the cells have proven to home to the damaged myocardium, functionality is limited by their poor engraftment at the site of injury, resulting in diffusion into the blood stream. This manuscript highlights a procedure that overcomes this obstacle with the use of a cell encapsulated hydrogel patch. The patch is fabricated prior to the surgical procedure and is placed on the injured myocardium immediately following the occlusion of the left coronary artery. To adhere the patch in place, biocompatible external fibrin glue is placed directly on top of the patch, allowing for it to dry to both the patch and the heart surface. This approach provides a novel adhesion method for the application of a delicate cell encapsulating therapeutic construct. PMID- 26132814 TI - Weak Micelle-Like Aggregation in Ternary Liquid Mixtures as Revealed by Conductivity, Surface Tension, and Light Scattering. AB - A very small concentration of NaBr is added to ternary, transparent, and thermodynamically stable mixtures of water, ethanol, and octanol. Measuring the electrical conductivity along lines with constant water to ethanol ratios reveals remarkable composition dependencies similar to those found in classical surfactant-based microemulsions. Indeed, light-scattering experiments along the same composition lines and additional surface tension measurements confirm the onset of aggregation and possibly direct, bicontinuous, and reversed structures in these surfactant-free systems such as in classical microemulsions. PMID- 26132816 TI - How are cancer and connective tissue diseases related to sarcoidosis? AB - PURPOSE OF REVIEW: Several studies have suggested an association between sarcoidosis and cancer, and between sarcoidosis and connective tissue diseases (CTDs). In this review, we discuss the evidence supporting and refuting these associations. RECENT FINDINGS: In terms of a cancer risk in sarcoidosis patients, the data are somewhat conflicting but generally show a very small increased risk. The data supporting an association between sarcoidosis and CTD are not as robust as for cancer. However, it appears that scleroderma is the CTD most strongly associated with sarcoidosis. SUMMARY: There are several important clinical and research-related implications of the association of sarcoidosis and CTDs. First, rigorous efforts should be made to exclude alternative causes for granulomatous inflammation before establishing a diagnosis of sarcoidosis. Second, the association between sarcoidosis and both cancer and CTDs may yield important insights into the immunopathogenesis of all three diseases. Finally, these data provide insight in answering a common question asked by sarcoidosis patients, 'Am I at an increased risk of developing cancer?' We believe that although there is an increased (relative) risk of cancer in sarcoidosis patients compared with the general population, that increased risk is quite small (low absolute risk). PMID- 26132815 TI - Using fMRI to Investigate Memory in Young Children Born Small for Gestational Age. AB - OBJECTIVES: Intrauterine growth restriction (IUGR) can lead to infants being born small for gestational age (SGA). SGA is associated with differences in brain anatomy and impaired cognition. We investigated learning and memory in children born SGA using neuropsychological testing and functional Magnetic Resonance Imaging (fMRI). STUDY DESIGN: 18 children born appropriate for gestational age (AGA) and 34 SGA born children (18 with and 16 without postnatal catch-up growth) participated in this study. All children were between 4 and 7 years old. Cognitive functioning was assessed by IQ and memory testing (Digit/Word Span and Location Learning). A newly developed fMRI picture encoding task was completed by all children in order to assess brain regions involved in memory processes. RESULTS: Neuropsychological testing demonstrated that SGA children had IQ's within the normal range but lower than in AGA and poorer performances across measures of memory. Using fMRI, we observed memory related activity in posterior parahippocampal gyrus as well as the hippocampus proper. Additionally, activation was seen bilaterally in the prefrontal gyrus. Children born SGA showed less activation in the left parahippocampal region compared to AGA. CONCLUSIONS: This is the first fMRI study demonstrating different brain activation patterns in 4-7 year old children born SGA, suggesting that intrauterine growth restriction continues to affect neural functioning in children later-on. PMID- 26132817 TI - Personalized medicine in idiopathic pulmonary fibrosis: facts and promises. AB - PURPOSE OF REVIEW: In this article, we summarize and discuss the most recent literature on personalized medicine in idiopathic pulmonary fibrosis (IPF), a chronic progressive and almost invariably lethal disease of unknown cause. This review is timely as major advances in our understanding of disease pathobiology and improvements in molecular techniques have recently led to the identification of potential surrogates of diagnosis, prognosis and response to treatment. RECENT FINDINGS: The most promising and advanced candidate biomarkers are presented based on their proposed mechanistic pathways (e.g. alveolar epithelial cell dysfunction, immune dysregulation, microbiome, extracellular matrix remodeling and fibroproliferation, epigenetic markers and metabolomics). Recent data suggest that components of the immune system may contribute to the development of IPF. A potential role for infections as a cofactor in disease development and progression or as a trigger in disease exacerbation has also recently been proposed. SUMMARY: Clinical management of IPF is unsatisfactory because of limited availability of truly effective therapies, lack of accurate predictors of disease behavior and absence of simple short-term measures of therapeutic response. A number of putative biomarkers have been identified in patients with IPF, although none has been validated to the standard necessary for their use in either therapeutic trials or clinical practice. Currently, ongoing prospective longitudinal studies will hopefully permit such validation. PMID- 26132818 TI - The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. AB - OBJECTIVES: Lignosulfonic acid (LA), a low-cost lignin-derived polyanionic macromolecule, was extensively studied for its anti-HIV and anti-HSV activity in various cellular assays, its mechanism of viral inhibition and safety profile as potential microbicide. RESULTS: LA demonstrated potent inhibitory activity of HIV replication against a wide range of R5 and X4 HIV strains and prevented the uptake of HIV by bystander CD4+ T cells from persistently infected T cells in vitro (IC50: 0.07 - 0.34 MUM). LA also inhibited HSV-2 replication in vitro in different cell types (IC50: 0.42 - 1.1 MUM) and in rodents in vivo. Furthermore, LA neutralized the HIV-1 and HSV-2 DC-SIGN-mediated viral transfer to CD4+ T cells (IC50: ~1 MUM). In addition, dual HIV-1/HSV-2 infection in T cells was potently blocked by LA (IC50: 0.71 MUM). No antiviral activity was observed against the non-enveloped viruses Coxsackie type B4 and Reovirus type 1. LA is defined as a HIV entry inhibitor since it interfered with gp120 binding to the cell surface of T cells. Pretreatment of PBMCs with LA neither increased expression levels of cellular activation markers (CD69, CD25 and HLA-DR), nor enhanced HIV-1 replication. Furthermore, we found that LA had non-antagonistic effects with acyclovir, PRO2000 or LabyA1 (combination index (CI): 0.46 - 1.03) in its anti-HSV-2 activity and synergized with tenofovir (CI: 0.59) in its anti HIV-1 activity. To identify mechanisms of LA resistance, we generated in vitro a mutant HIV-1 NL4.3LAresistant virus, which acquired seven mutations in the HIV-1 envelope glycoproteins: S160N, V170N, Q280H and R389T in gp120 and K77Q, N113D and H132Y in gp41. Additionally, HIV-1 NL4.3LAresistant virus showed cross resistance with feglymycin, enfuvirtide, PRO2000 and mAb b12, four well-described HIV binding/fusion inhibitors. Importantly, LA did not affect the growth of vaginal Lactobacilli strains. CONCLUSION: Overall, these data highlight LA as a potential and unique low-cost microbicide displaying broad anti-HIV and anti-HSV activity. PMID- 26132820 TI - The Sound of Voice: Voice-Based Categorization of Speakers' Sexual Orientation within and across Languages. AB - Empirical research had initially shown that English listeners are able to identify the speakers' sexual orientation based on voice cues alone. However, the accuracy of this voice-based categorization, as well as its generalizability to other languages (language-dependency) and to non-native speakers (language specificity), has been questioned recently. Consequently, we address these open issues in 5 experiments: First, we tested whether Italian and German listeners are able to correctly identify sexual orientation of same-language male speakers. Then, participants of both nationalities listened to voice samples and rated the sexual orientation of both Italian and German male speakers. We found that listeners were unable to identify the speakers' sexual orientation correctly. However, speakers were consistently categorized as either heterosexual or gay on the basis of how they sounded. Moreover, a similar pattern of results emerged when listeners judged the sexual orientation of speakers of their own and of the foreign language. Overall, this research suggests that voice-based categorization of sexual orientation reflects the listeners' expectations of how gay voices sound rather than being an accurate detector of the speakers' actual sexual identity. Results are discussed with regard to accuracy, acoustic features of voices, language dependency and language specificity. PMID- 26132819 TI - Genetic Variability of Bovine Viral Diarrhea Virus and Evidence for a Possible Genetic Bottleneck during Vertical Transmission in Persistently Infected Cattle. AB - Bovine viral diarrhea virus (BVDV), a Pestivirus in the family Flaviviridae, is an economically important pathogen of cattle worldwide. The primary propagators of the virus are immunotolerant persistently infected (PI) cattle, which shed large quantities of virus throughout life. Despite the absence of an acquired immunity against BVDV in these PI cattle there are strong indications of viral variability that are of clinical and epidemiological importance. In this study the variability of E2 and NS5B sequences in multiple body compartments of PI cattle were characterized using clonal sequencing. Phylogenetic analyses revealed that BVDV exists as a quasispecies within PI cattle. Viral variants were clustered by tissue compartment significantly more often than expected by chance alone with the central nervous system appearing to be a particularly important viral reservoir. We also found strong indications for a genetic bottleneck during vertical transmission from PI animals to their offspring. These quasispecies analyses within PI cattle exemplify the role of the PI host in viral propagation and highlight the complex dynamics of BVDV pathogenesis, transmission and evolution. PMID- 26132821 TI - Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring. AB - Several in vivo pre-clinical studies in Polycystic Kidney Disease (PKD) utilize orthologous rodent models to identify and study the genetic and molecular mechanisms responsible for the disease, and are very convenient for rapid drug screening and testing of promising therapies. A limiting factor in these studies is often the lack of efficient non-invasive methods for sequentially analyzing the anatomical and functional changes in the kidney. Magnetic resonance imaging (MRI) is the current gold standard imaging technique to follow autosomal dominant polycystic kidney disease (ADPKD) patients, providing excellent soft tissue contrast and anatomic detail and allowing Total Kidney Volume (TKV) measurements.A major advantage of MRI in rodent models of PKD is the possibility for in vivo imaging allowing for longitudinal studies that use the same animal and therefore reducing the total number of animals required. In this manuscript, we will focus on using Ultra-high field (UHF) MRI to non-invasively acquire in vivo images of rodent models for PKD. The main goal of this work is to introduce the use of MRI as a tool for in vivo phenotypical characterization and drug monitoring in rodent models for PKD. PMID- 26132822 TI - Functional Repair of Rat Corticospinal Tract Lesions Does Not Require Permanent Survival of an Immunoincompatible Transplant. AB - Cell transplantation is one of the most promising strategies for repair of human spinal cord injuries. Animal studies from a number of laboratories have shown that transplantation of olfactory ensheathing cells cultured from biopsies of the olfactory bulb mediate axonal regeneration and remyelination and restore lost functions in spinal cord injuries. For translation from small laboratory experimental injuries to the large spinal cord injuries encountered in human patients the numbers of cells that can be obtained from a patient's own olfactory bulb becomes a serious limiting factor. Furthermore, removal of an olfactory bulb requires invasive surgery and risks unilateral anosmia. We here report that xenografted mouse bulbar olfactory ensheathing cells immunoprotected by daily cyclosporine restore directed forepaw reaching function in rats with chronic C1/2 unilateral corticospinal tract lesions. Once function had been established for 10 days, cyclosporine was withdrawn. Thirteen out of 13 rats continued to increase directed forepaw reaching. Immunohistochemistry shows that in all cases neurofilament-positive axons were present in the lesion, but that the grafted cells had been totally rejected. This implies that once grafted cells have acted as bridges for axon regeneration across the lesion site their continued presence is no longer necessary for maintaining the restored function. This raises the possibility that in the future a protocol of temporary immunoprotection might allow for the use of the larger available numbers of immunoincompatible allografted cells or cell lines, which would avoid the need for removing a patient's olfactory bulb. PMID- 26132823 TI - Mycobacterium Bovis Abdominal Tuberculosis in a Young Child. AB - Abdominal tuberculosis can mimic many processes resulting in delayed diagnosis and unnecessary surgery. We describe a child of Moroccan parents with an abdominal mass caused by Mycobacterium bovis. The case stresses the need for increased awareness of M. bovis tuberculosis (TB) in general and extrapulmonary TB in the setting of foreign-born individuals who travel periodically to TB endemic regions. PMID- 26132824 TI - Meningomyeloradiculitis as an Unusual Presentation of Neuroborreliosis in Childhood. AB - We report a pediatric case of Lyme neuroborreliosis-associated meningomyeloradiculitis with atypical manifestations and negative initial cerebrospinal fluid borrelial antibodies. Transverse myelitis and painful radiculoneuritis have rarely been described in pediatric neuroborreliosis. Clinical manifestations are wide ranging and nonspecific, and the serologic diagnosis is often delayed in the acute phase. PMID- 26132825 TI - Reactivation of Human Herpes Virus-6 After Pediatric Stem Cell Transplantation: Risk Factors, Onset, Clinical Symptoms and Association With Severity of Acute Graft-Versus-Host Disease. AB - BACKGROUND AND METHODS: To study clinical symptoms, timing and consequences of human herpesvirus-6 (HHV-6) reactivation after pediatric allogeneic stem cell transplantation (SCT), HHV-6 was investigated by plasma polymerase chain reaction in a cohort of 106 pediatric SCT recipients. RESULTS: HHV-6 viremia was detected post-SCT in 48% of the patients with a median time of onset at 20 days after SCT. In week 3 and 4 post-SCT, HHV-6 is the most common infectious agent detected. In up to 30% of the patients with fever of unknown origin, HHV-6 was the only detected infectious agent to explain fever. Patients transplanted with an unrelated donor or receiving serotherapy were at increased risk of HHV-6 reactivation. The onset of HHV-6 reactivation coincided with the appearance of lymphocytes and monocytes in peripheral blood. Treatment with alemtuzumab (MabCampath) delayed both lymphocyte and monocyte engraftment and, concomitantly, onset of HHV-6 reactivation was delayed in those cases. HHV-6 reactivation was not associated with an increased incidence of acute graft-versus-host disease (GvHD). However, progression to grade II-IV GvHD was in 9 of 10 patients associated with HHV-6 reactivation before GvHD (P = 0.006) and HHV-6 was the only infection with such an association. CONCLUSIONS: HHV-6 frequently reactivates after pediatric SCT around the time of mononuclear cell engraftment and is associated with an increased severity of GvHD. HHV-6 may explain fever of unknown origin in 30% of the patients early after SCT. Assessment of HHV-6 reactivation in patients early after SCT can be instrumental for clinical decision making. PMID- 26132826 TI - Viral Load in Infants Hospitalized for Respiratory Syncytial Virus Bronchiolitis Correlates with Recurrent Wheezing at Thirty-Six-Month Follow-Up. AB - The relationship between viral infection, host immune response in infants with respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing is discussed. We measured RSV-RNA load and interferon-lambda1-3 expression in the nasopharyngeal washings from 68 infants hospitalized for RSV bronchiolitis, and wheezing was assessed 36 months after the first episode of bronchiolitis. Higher RSV-RNA load and higher interferon-lambda2/3 levels were found in children with recurrent wheezing at 36-month follow-up. PMID- 26132827 TI - Effects of Caffeine Supplementation on Plasma and Blood Mononuclear Cell Interleukin-10 Levels After Exercise. AB - This study compared the response of interleukin (IL)-10, and also of IL-6 and IL 12 p40, to exercise and caffeine supplementation between plasma and blood mononuclear cells (BMNCs). Participants in the study (n = 28) were randomly allocated in a double-blind fashion to either caffeine (n = 14) or placebo (n = 14) treatments. One hour before completing a 15-km run competition, athletes took 6 mg/kg body mass of caffeine or a placebo. Plasma and BMNCs were purified from blood samples taken before and after competition. Concentrations of interleukins (IL-10, IL-6, and IL-12 p40), cyclic adenosine monophosphate (cAMP), caffeine, adrenaline, and cortisol were measured in plasma. IL-10, IL-6, and IL-12 p40 and cAMP levels were also determined in BMNCs. Exercise induced significant increases in IL-6 and IL-10 plasma levels, with higher increases in the caffeine supplemented group. After 2-hr recovery, these levels returned to almost preexercise values. However, no effect of caffeine on BMNC cytokines was observed. IL-10, IL-6, and IL-12 p40 levels in BMNCs increased mainly at 2 hr postexercise. cAMP levels increased postexercise in plasma and after recovery in BMNCs, but no effects of caffeine were observed. In conclusion, caffeine did not modify cytokine levels in BMNCs in response to exercise. However, higher increases of IL-10 were observed in plasma after exercise in the supplemented participants, which could suppose an enhancement of the anti-inflammatory properties of exercise. PMID- 26132829 TI - Correction to "Spontaneous Formation of Photochromic Coatings Made of Reversible Microfibrils and Nanofibrils on an Elastomer Substrate". PMID- 26132830 TI - Kinetic Energy of Tornadoes in the United States. AB - Tornadoes can cause catastrophic destruction. Here total kinetic energy (TKE) as a metric of destruction is computed from the fraction of the tornado path experiencing various damage levels and a characteristic wind speed for each level. The fraction of the path is obtained from a model developed for the Nuclear Regulatory Commission that combines theory with empirical data. TKE is validated as a useful metric by comparing it to other indexes and loss indicators. Half of all tornadoes have TKE exceeding 62.1 GJ and a quarter have TKE exceeding 383.2 GJ. One percent of the tornadoes have TKE exceeding 31.9 TJ. April has more energy than May with fewer tornadoes; March has more energy than June with half as many tornadoes. September has the least energy but November and December have the fewest tornadoes. Alabama ranks number one in terms of tornado energy with 2.48 PJ over the period 2007-2013. TKE can be used to help better understand the changing nature of tornado activity. PMID- 26132831 TI - Biogenic amines at a low level of evolution: Production, functions and regulation in the unicellular Tetrahymena. AB - The unicellular eukaryote Tetrahymena synthesize, store and secrete biogenic amines (histamine, serotonin, epinephrine, dopamine, melatonin) and also can take up amines from the milieu. It also has (G-protein-coupled) receptors (binding sites) for these amines as well, as second messengers. The factors infuencing the mentioned processes are shown. For certain amines the genes and the coded enzymes are demonstrated. The amines influence phagocytosis, cell division, ciliary regeneration, glucose metabolism and chemotaxis. There are interhormone actions between the amines, and between the amines and other hormones produced by Tetrahymena. The critical review discusses the role of amines in the early stages of evolution and compares this to their functions in mammals. It tries to give answer how and why biogenic amines were selected to hormones, and why new functions formed for them in higher ranked animals, preserving also the ancient ones. PMID- 26132828 TI - Structure and mechanism of a bacterial host-protein citrullinating virulence factor, Porphyromonas gingivalis peptidylarginine deiminase. AB - Citrullination is a post-translational modification of higher organisms that deiminates arginines in proteins and peptides. It occurs in physiological processes but also pathologies such as multiple sclerosis, fibrosis, Alzheimer's disease and rheumatoid arthritis (RA). The reaction is catalyzed by peptidylarginine deiminases (PADs), which are found in vertebrates but not in lower organisms. RA has been epidemiologically associated with periodontal disease, whose main infective agent is Porphyromonas gingivalis. Uniquely among microbes, P. gingivalis secretes a PAD, termed PPAD (Porphyromonas peptidylarginine deiminase), which is genetically unrelated to eukaryotic PADs. Here, we studied function of PPAD and its substrate-free, substrate-complex, and substrate-mimic-complex structures. It comprises a flat cylindrical catalytic domain with five-fold alpha/beta-propeller architecture and a C-terminal immunoglobulin-like domain. The PPAD active site is a funnel located on one of the cylinder bases. It accommodates arginines from peptide substrates after major rearrangement of a "Michaelis loop" that closes the cleft. The guanidinium and carboxylate groups of substrates are tightly bound, which explains activity of PPAD against arginines at C-termini but not within peptides. Catalysis is based on a cysteine-histidine-asparagine triad, which is shared with human PAD1-PAD4 and other guanidino-group modifying enzymes. We provide a working mechanism hypothesis based on 18 structure-derived point mutants. PMID- 26132832 TI - Occurrence of Fusarium verticillioides and Fusarium musae on banana fruits marketed in Hungary. AB - Fusarium strains were isolated from rotten banana fruit imported into Hungary from some African and some Neotropical countries. The strains were identified using morphological features, 2-benzoxazolinone tolerance, translation elongation factor (EF-1alpha) sequences and inter simple sequence repeat (ISSR) analysis. All strains from Africa proved to be F. verticillioides whereas the strains from the Neotropics are Fusarium musae. According to the PCR proof and the fumonisin toxin measurement F. musae strains cannot produce any fumonisins (FB1-4). PMID- 26132833 TI - A yeast two-hybrid screen reveals a strong interaction between the Legionella chaperonin Hsp60 and the host cell small heat shock protein Hsp10. AB - L. pneumophila is an intracellular bacterium that replicates inside a membrane bound vacuole called Legionella-containing vacuole (LCV), where it plentifully liberates its HtpB chaperonin. From LCV, HtpB reaches the host cell cytoplasm, where it interacts with SAMDC, a cytoplasmic protein required for synthesis of host polyamines that are important for intracellular growth of L. pneumophila. Additionally, cytoplasmic expression of HtpB in S. cerevisiae induces pseudohyphal growth, and in mammalian cells recruits mitochondria to LCV, and modifies actin microfilaments organization. This led us to hypothesize here that HtpB recruits a protein(s) from eukaryotic cells that is involved in the emergence of the aforementioned phenotypes. To identify this protein, a commercially available HeLa cDNA library was screened using a yeast two-hybrid system. Approximately 5*10(6) yeast clones carrying HeLa cDNA library plasmid were screened. Twenty-one positive clones were identified. DNA sequence analysis revealed that all of these positive clones encoded the mammalian small heat shock protein Hsp10. Based on the fact that chaperonions are required to interact with co-chaperonins to function properly in protein folding, we believe that HtpB recruits the host cell Hsp10 to appropriately interact with SAMDC and to induce the multifunction phenotypes deemed important in L. pneumophila pathogenesis. PMID- 26132834 TI - Status of soluble ST2 levels in serum of HTLV-1 infected individuals. AB - ST2 is a member of IL-1 receptor family expressed on Th2 cells and regulates Th2 responces. The gene of ST2 encodes soluble ST2 (sST2) and the transmembrane ST2 (ST2L) isoforms through alternative mRNA splicing. The discovery of IL33/ ST2 signaling pathway, has drawn a great scientific attention to this system. sST2 has been shown to be an indacating factor in various infl ammatory conditions. This study aims to evaluate serum sST2 levels in HTLV-1 infected patients. This study included 49 HTLV-1 seropositive cases of which 14 were sympthomatic. Controls consisted of 30 healthy volunteers. sST2 level was measured using a quantitative ELISA assay and the results of the study groups were compared. Corroborating the previous reports, sST2 was lower in females (P = 0.003). The sST2 levels was slightly increased in HTLV-1 patients, though such increase was not statistically significant (P = 0.91), in addition sST2 level did not correlate significantly to the disease duration (P = 0.78). Despite some other chronic viral infection, HTLV-1 seems not to induce high serum sST2. However owing to relatively high normal variation of sST2 levels and rather small sample size, we stongly recommend further reseach with preferably larger sample size to evalute sST2 in HTLV-1 infected patients. PMID- 26132835 TI - Molecular typing, pathogenicity factor genes and antimicrobial susceptibility of vancomycin resistant enterococci in Belgrade, Serbia. AB - In this study the distribution of species and antimicrobial resistance among vancomycin resistant enterococci (VRE) recovered from clinical specimens obtained from five hospitals in Belgrade was analyzed. Strains were further characterized by pulsed-field gel electrophoresis (PFGE). Polymerase chain reaction (PCR) was used to investigate the presence of vanA and vanB genes and pathogenicity factor genes. Identification of 194 VRE isolates revealed 154 Enterococcus faecium, 21 Enterococcus faecalis, 10 Enterococcus raffinosus and 9 Enterococcus gallinarum. This study revealed existence of 8 major clones of VRE. PCR determined vanA gene to be present in all of the VRE studied. Esp and hyl genes were present in 29.22% and 27.92% of E. faecium, respectively, and in 76.19% and 0 of E. faecalis, respectively. Esp and hyl genes were not found more frequently in members of predominant clones of E. faecium than in single isolates; nor was their presence connected to invasiveness. PMID- 26132836 TI - Simkania negevensis: Is it a real respiratory pathogen? AB - Simkania negevensis, a recently discovered Chlamydia-like organism, has been associated with respiratory infections such as pneumonia, bronchiolitis and chronic obstructive pulmonary disease in children and adults. The aim of the present study was to evaluate S. negevensis in the etiology of pediatric community-acquired pneumonia, bronchiolitis and asthma exacerbation in our region. Overall, 102 patients and 46 healthy controls were included in the study. S. negevensis was investigated by real time PCR (Primer Design, UK) in nasopharyngeal swab samples. It failed to be detected in either the study or control group. In conclusion, our results suggest that S. negevensis is not an important respiratory pathogen in our region. PMID- 26132837 TI - Human vomeronasal epithelium development: An immunohistochemical overview. AB - The vomeronasal organ (VNO) is the receptor structure of the vomeronasal system (VNS) in vertebrates. It is found bilaterally in the submucosa of the inferior part of the nasal septum. There are ongoing controversies regarding the functionality of this organ in humans. In this study we propose the immunohistochemical evaluation of changes in components of the human vomeronasal epithelium during foetal development. We used 45 foetuses of different age, which were included in three age groups. After VNO identification immunohistochemical reactions were performed using primary antibodies against the following: neuron specific enolase, calretinin, neurofilament, chromogranin, synaptophysin, cytokeratin 7, pan-cytokeratin and S100 protein. Digital slides were obtained and following colorimetric segmentation, surface area measurements were performed. The VNO was found in less than half of the studied specimens (42.2%). Neuron specific enolase and calretinin immunoexpression showed a decreasing trend with foetal age, while the other neural/neuroendocrine markers were negative in all specimens. Cytokeratin 7 expression increased with age, while Pan-Ctk had no significant variations. S100 protein immunoexpression also decreased around the VNO. The results of the present work uphold the theory of regression of the neuroepithelium that is present during initial stages of foetal development. PMID- 26132838 TI - Diversity and ecological tolerance of bacteria isolated from the rhizosphere of halophyton plants living nearby Kiskunsag soda ponds, Hungary. AB - Many halophytes and halophilic microorganisms are capable to adapt to the extremities of saline habitats. This study reveals the taxonomic diversity and ecological tolerance of bacteria isolated from the rhizosphere of three different halophytes (Bolboschoenus maritimus, Puccinellia limosa and Aster tripolium) living in the vicinity of Kiskunsag soda ponds. Following a sampling in September 2013, altogether 76 bacterial strains were isolated using two different media. The strains were identified on the basis of 16S rRNA gene sequencing following ARDRA grouping. Salt and pH tolerance of the strains were examined by measuring their growth in broths containing 0-15% NaCl (w/V) and characterized with pH 7-12 values. Among the strains genera of Anaerobacillus, Bacillus and Exiguobacterium (Firmicutes), Agromyces, Isoptericola, Microbacterium, Micrococcus, Nocardiopsis, Nesterenkonia and Streptomyces (Actinobacteria), Halomonas and Idiomarina (Proteobacteria) and Anditalea (Bacteroidetes) were identified. The Bolboschoenus and Puccinellia samples characterized with the highest pH and electric conductivity values were dominated by Bacillus, Halomonas and Nesterenkonia, respectively. The salt tolerance of the bacterial strains was strongly dependent on the sampling location and plant species. In contrast, growth of bacterial strains in broths with alkaline pH values was more balanced. The strains from the Puccinellia sample showed the widest salt and pH tolerance. PMID- 26132839 TI - Seroprevalence and entomological study on Chikungunya virus at the Croatian littoral. AB - During 2011-2012, a total of 1008 serum samples from randomly selected inhabitants of seven Croatian counties located on the Adriatic Coast were tested for the presence of chikungunya virus (CHIKV) IgG antibodies using indirect immunofluorescence assay. Nine participants (0.9%) from four counties were found to be seropositive to CHIKV. Seroprevalence varied from 0.5% to 1.8% between counties. Additionally, a total of 3,699 mosquitoes were captured in 126 localities from August 16 to September 24, 2011. Three mosquito species were found: Ae. albopictus (3010/81.4%), Cx. pipiens (688/18.6%) and only one specimen of the Cs. longiareolata. Female mosquitoes (N = 1,748) were pooled. All pools tested negative for CHIKV RNA using a real-time RT-PCR. PMID- 26132840 TI - Sustained Benefit from ivacaftor demonstrated by combining clinical trial and cystic fibrosis patient registry data. AB - RATIONALE: In clinical trials, patients with cystic fibrosis and a G551D mutation who received ivacaftor experienced improvements in pulmonary and nutritional outcomes. However, whether these improvements reflect a change in disease trajectory cannot be determined without longer-term analyses with an appropriate comparator population. OBJECTIVES: To examine, over a 3-year period, whether ivacaftor therapy affects pulmonary function and nutritional measures in patients with CF with a G551D mutation compared with patients with CF who are homozygous for the F508del mutation. METHODS: A propensity score was used to match patients with CF greater than or equal to 6 years of age who have a G551D mutation and received ivacaftor in clinical trials for up to 144 weeks with data from patients in the U.S. Cystic Fibrosis Foundation Patient Registry who are homozygous for the F508del mutation. Matching was based on variables including age, sex, weight for age, height for age, body mass index for age, % predicted FEV1, and chronic therapies (dornase alfa, inhaled antibiotics, inhaled and oral corticosteroids). MEASUREMENTS AND MAIN RESULTS: By calculating the annual estimated rate of decline in lung function for G551D patients receiving ivacaftor and comparing it with the rate of decline in lung function for matched F508del control patients, we show that the rate of lung function decline in G551D ivacaftor-treated patients was slower by nearly half. Moreover, treatment with ivacaftor is shown to improve body mass index and weight-for-age z scores for G551D patients over the 3-year analysis period. CONCLUSIONS: These findings suggest that ivacaftor is a disease-modifying therapy for the treatment of cystic fibrosis. PMID- 26132841 TI - Colossal Room-Temperature Electrocaloric Effect in Ferroelectric Polymer Nanocomposites Using Nanostructured Barium Strontium Titanates. AB - The electrocaloric effect (ECE) refers to conversion of thermal to electrical energy of polarizable materials and could form the basis for the next-generation refrigeration and power technologies that are highly efficient and environmentally friendly. Ferroelectric materials such as ceramic and polymer films exhibit large ECEs, but each of these monolithic materials has its own limitations for practical cooling applications. In this work, nanosized barium strontium titanates with systematically varied morphologies have been prepared to form polymer nanocomposites with the ferroelectric polymer matrix. The solution processed polymer nanocomposites exhibit an extraordinary room-temperature ECE via the synergistic combination of the high breakdown strength of a ferroelectric polymer matrix and the large change of polarization with temperature of ceramic nanofillers. It is found that a sizable ECE can be generated under both modest and high electric fields, and further enhanced greatly by tailoring the morphology of the ferroelectric nanofillers such as increasing the aspect ratio of the nanoinclusions. The effect of the geometry of the nanofillers on the dielectric permittivity, polarization, breakdown strength, ECE and crystallinity of the ferroelectric polymer has been systematically investigated. Simulations based on the phase-field model have been carried out to substantiate the experimental results. With the remarkable cooling energy density and refrigerant capacity, the polymer nanocomposites are promising for solid-state cooling applications. PMID- 26132842 TI - Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats. AB - Environmental enrichment (EE) exerts beneficial effects on brain plasticity, cognition, and anxiety/depression, leading to a brain that can counteract deficits underlying various brain disorders. Because the complexity of the EE commonly used makes it difficult to identify causal aspects, we examined possible factors using a 2 * 2 design with social EE (two vs. six rats) and physical EE (physically enriched vs. nonenriched). For the first time, we demonstrate that social and physical EE have differential effects on brain plasticity, cognition, and ultrasonic communication. Expectedly, physical EE promoted neurogenesis in the dentate gyrus of the hippocampal formation, but not in the subventricular zone, and, as a novel finding, affected microRNA expression levels, with the activity-dependent miR-124 and miR-132 being upregulated. Concomitant improvements in cognition were observed, yet social deficits were seen in the emission of prosocial 50-kHz ultrasonic vocalizations (USV) paralleled by a lack of social approach in response to them, consistent with the intense world syndrome/theory of autism. In contrast, social EE had only minor effects on brain plasticity and cognition, but led to increased prosocial 50-kHz USV emission rates and enhanced social approach behavior. Importantly, social deficits following physical EE were prevented by additional social EE. The finding that social EE has positive whereas physical EE has negative effects on social behavior indicates that preclinical studies focusing on EE as a potential treatment in models for neuropsychiatric disorders characterized by social deficits, such as autism, should include social EE in addition to physical EE, because its lack might worsen social deficits. PMID- 26132843 TI - Four-component relativistic DFT calculations of (77) Se NMR chemical shifts: A gateway to a reliable computational scheme for the medium-sized organoselenium molecules. AB - A versatile high-accuracy computational scheme for the (77) Se nuclear magnetic resonance (NMR) chemical shifts of the medium-sized organoselenium compounds is suggested within a framework of a full four-component relativistic density functional theory (DFT). The main accuracy factors (DFT functionals, relativistic geometry, vibrational corrections, and solvent effects) are addressed. The best result is achieved with NMR-oriented KT2 functional of Keal-Tozer characterized by a fairly small error of only 30 ppm for the span of about 1700 ppm (<2%). PMID- 26132845 TI - Nursing and Medical Perceptions of a Hospital Rapid Response System: New Process But Same Old Game? AB - Perhaps no other patient safety intervention depends so acutely on effective interprofessional teamwork for patient survival than the hospital rapid response system. Yet, little is known about nurse-physician relationships when rescuing at risk patients. This study compared nursing and medical staff perceptions of a mature rapid response system at a large tertiary hospital. Findings indicate that the rapid response system may be failing to address a hierarchical culture and systems-level barriers to early recognition and response to patient deterioration. PMID- 26132844 TI - Marine Peptides: Bioactivities and Applications. AB - Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products. PMID- 26132847 TI - Alexander Rich (November 15, 1924-April 27, 2015). PMID- 26132846 TI - Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways. AB - One of the promising possibilities of the clinical application of cold plasma, so called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment. PMID- 26132849 TI - Mechanism of Ascorbate-Induced Cell Death in Human Pancreatic Cancer Cells: Role of Bcl-2, Beclin 1 and Autophagy. AB - The present study investigates the anticancer effect of ascorbate in MIA-PaCa-2 human pancreatic cancer cells using both in vitro and in vivo models, with a focus on assessing the role of oxidative stress and autophagy as important mechanistic elements in its anticancer actions. We showed that ascorbate suppresses the growth of human pancreatic cancer cells via the induction of oxidative stress and caspase-independent cell death. Ascorbate induces the formation of autophagosomes and the presence of autophagy inhibitors suppresses ascorbate-induced cell death. These data suggest that the induction of autophagosome formation contributes to ascorbate-induced pancreatic cancer cell death. PMID- 26132848 TI - Contact- and Protein Transfer-Dependent Stimulation of Assembly of the Gliding Motility Machinery in Myxococcus xanthus. AB - Bacteria engage in contact-dependent activities to coordinate cellular activities that aid their survival. Cells of Myxococcus xanthus move over surfaces by means of type IV pili and gliding motility. Upon direct contact, cells physically exchange outer membrane (OM) lipoproteins, and this transfer can rescue motility in mutants lacking lipoproteins required for motility. The mechanism of gliding motility and its stimulation by transferred OM lipoproteins remain poorly characterized. We investigated the function of CglC, GltB, GltA and GltC, all of which are required for gliding. We demonstrate that CglC is an OM lipoprotein, GltB and GltA are integral OM beta-barrel proteins, and GltC is a soluble periplasmic protein. GltB and GltA are mutually stabilizing, and both are required to stabilize GltC, whereas CglC accumulate independently of GltB, GltA and GltC. Consistently, purified GltB, GltA and GltC proteins interact in all pair-wise combinations. Using active fluorescently-tagged fusion proteins, we demonstrate that GltB, GltA and GltC are integral components of the gliding motility complex. Incorporation of GltB and GltA into this complex depends on CglC and GltC as well as on the cytoplasmic AglZ protein and the inner membrane protein AglQ, both of which are components of the gliding motility complex. Conversely, incorporation of AglZ and AglQ into the gliding motility complex depends on CglC, GltB, GltA and GltC. Remarkably, physical transfer of the OM lipoprotein CglC to a DeltacglC recipient stimulates assembly of the gliding motility complex in the recipient likely by facilitating the OM integration of GltB and GltA. These data provide evidence that the gliding motility complex in M. xanthus includes OM proteins and suggest that this complex extends from the cytoplasm across the cell envelope to the OM. These data add assembly of gliding motility complexes in M. xanthus to the growing list of contact-dependent activities in bacteria. PMID- 26132850 TI - Gradient x Isocratic Elution CCC on the Isolation of Verbascoside and Other Phenylethanoids: Influence of the Complexity of the Matrix. AB - Verbascoside is a phenylethanoid glycoside widely distributed in nature, especially among the order Lamiales, occurring in numerous plants that are constituents of folk medicine preparations. This natural compound, previously isolated by our group from the ethyl acetate extract of Lantana trifolia using the gradient approach in countercurrent chromatography, was now isolated from the butanol extract of the same plant and from Lippia alba f. intermedia (Verbenaceae) using countercurrent chromatography in either gradient or isocratic elution modes. The ethyl acetate extract of L. alba, rich in phenylethanoids and flavonoids, was fractionated using countercurrent chromatography in the step gradient elution approach. The four-step solvent system was composed of n-hexane ethyl acetate-n-butanol-water (4 : 10 : X : 10), where X = 1 (solvent system A), 3 (solvent system B), 5 (solvent system C), and 7 (solvent system D), and allowed for the isolation of verbascoside along with other phenylethanoids and flavonoids from both plants. Verbascoside and 2'-O-beta-apiosylverbascoside were further isolated from the n-butanol extract of L. trifolia using the solvent system ethyl acetate-n-butanol-water 10 : 2 : 10 on an isocratic run. The difference in the complexity of the two plant extracts demanded different purification steps, which included a second high-speed countercurrent chromatography purification using the isocratic elution mode. PMID- 26132851 TI - Piperine Congeners as Inhibitors of Vascular Smooth Muscle Cell Proliferation. AB - Successful vascular healing after percutaneous coronary interventions is related to the inhibition of abnormal vascular smooth muscle cell proliferation and efficient re-endothelialization. In the search for vascular smooth muscle cell anti-proliferative agents from natural sources we identified piperine (1), the main pungent constituent of the fruits from Piper nigrum (black pepper). Piperine inhibited vascular smooth muscle cell proliferation with an IC50 of 21.6 uM, as quantified by a resazurin conversion assay. Investigations of ten piperamides isolated from black pepper fruits and 15 synthesized piperine derivatives resulted in the identification of three potent vascular smooth muscle cell proliferation inhibitors: the natural alkaloid pipertipine (4), and the two synthetic derivatives (2E,4E)-N,N-dibutyl-5-(3,5-dimethoxyphenyl)penta-2,4 dienamide (14) and (E)-N,N-dibutyl-3-(naphtho[2,3-d][1,3]dioxol-5-yl)acrylamide (20). They showed IC50 values of 3.38, 6.00, and 7.85 uM, respectively. Furthermore, the synthetic compound (2E,4E)-5-(4-fluorophenyl)-1-(piperidin-1 yl)penta-2,4-dien-1-one (12) was found to be cell type selective, by inhibiting vascular smooth muscle cell proliferation with an IC50 of 11.8 uM without influencing the growth of human endothelial cells. PMID- 26132852 TI - Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MS. AB - A quantitative assay for determination of the main bufadienolides bersaldegenin-1 acetate (1), bersaldegenin-3-acetate (2), bryophyllin A (3), and bersaldegenin 1,3,5-orthoacetate (4) in Bryophyllum pinnatum leaves and manufactured products was developed and validated. The assay involved extraction by pressurised liquid extraction, followed by quantification by ultrahigh performance liquid chromatography-tandem mass spectroscopy. The ultrahigh performance liquid chromatography-tandem mass spectroscopy method was applied to various batches of leaves harvested on several dates from plants grown at two locations (Brazil and Germany). In addition, press juices prepared from plants cultivated in Germany and Brazil were analysed. The total bufadienolide content ranged from 16.28 to 40.50 mg/100 g dry weight in leaves from plants grown in Brazil. The total content of these four bufadienolides was significantly lower in plants cultivated in Germany (3.78-12.49 mg/100 g dry weight, resp.). The total amounts of bufadienolides were 0.091-0.163 mg/100 mL and 0.89-1.16 mg/100 mL in press juices obtained from plants cultivated in Germany and Brazil, respectively. When analysing single leaves from individual plants, the content of bufadienolides was markedly higher in young leaves. For comparative purposes, the content of these bufadienolides was also determined in Bryophyllum daigremontianum and Bryophyllum tubiflorum. Bersaldegenin-1,3,5-orthoacetate (4) was predominant in the leaves of B. daigremontianum and in the stems of B. tubiflorum, while the leaves of B. tubiflorum contained very low amounts of 1-4. PMID- 26132853 TI - New Bioactive Lupane Triterpene Coumaroyl Esters Isolated from Buxus cochinchinensis. AB - Five new lupane triterpene coumaroyl esters (1-5), together with betulin (6) and a known Buxus alkaloid, N-3-benzoyldihydrocyclomicrophylline F (7), were isolated from a CHCl3-soluble partition of a methanol extract of Buxus cochinchinensis Pierre ex Gagnep. (Buxaceae) collected in Vietnam. Isolation work was monitored using human colon cancer cells (HT-29). The structures of the new compounds (1-5) were determined on the basis of spectroscopic data interpretation. In addition to their cytotoxicity against HT-29 cells and nuclear factor-kappa B (p65) inhibitory activity in an enzyme-linked immunosorbent assay, all isolates as well as two semisynthetic compounds derived from betulin and 5, respectively, were also evaluated for their in vitro antiplasmodial activities against the drug resistant Dd2 strain of Plasmodium falciparum and antifungal effects on the growth of the pathogenic yeast Candida albicans. The new lupane triterpene coumaroyl esters (1-5), along with a betulin derivative and the known Buxus alkaloid, were found to show significant in vitro antimalarial activities, with IC50 values ranging from 0.26 to 2.07 uM. PMID- 26132854 TI - Gamma-Terpinene Modulates Acute Inflammatory Response in Mice. AB - The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this study was to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gamma-terpinene displayed reduced paw edema induced by carrageenan from 1-24 h after challenge. A similar reduction was observed when gamma-terpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophil migration as well as the production of interleukin-1beta and tumor necrosis factor-alpha when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties. PMID- 26132855 TI - Imperialine and Verticinone from Bulbs of Fritillaria wabuensis Inhibit Pro inflammatory Mediators in LPS-stimulated RAW 264.7 Macrophages. AB - The bulbs of plants belonging to the Fritillaria cirrhosa-group have been used as antitussive and expectorant herbs in traditional Chinese medicine for thousands of years. In this study, we isolated two isomers of verticinone and imperialine, steroidal alkaloids belonging to the cevanine group, from bulbs of Fritillaria wabuensis, which is a part of the Fritillaria cirrhosa group, and investigated their anti-inflammatory effects and relative mechanisms on lipopolysaccharide stimulated RAW 264.7 macrophages. Our results clearly demonstrate that verticinone or imperialine could dose-dependently inhibit nitric oxide production and also suppress inducible nitric oxide synthase and cyclooxygenase-2 expressions. In addition, verticinone or imperialine suppress the production of pro-inflammatory cytokines in a dose dependent manner, such as tumor necrosis factor-alpha and interleukin-1beta. The effect of verticinone and imperialine on the activation of nuclear factor-kappaB was also evaluated. The phosphorylation of nuclear factor-kappaB stimulated with LPS is also down-regulated by verticinone or imperialine in a concentration dependent manner, which coincided with the inhibition of phosphorylation forms of inhibitory kappaB-alpha, a crucial inhibitory factor of nuclear factor-kappaB. Generally, the anti inflammatory effects and mechanisms of verticinone and imperialine are mediated by the inhibition of the nuclear factor-kappaB activation signaling pathway. According to the results of our researches, verticinone and imperialine may present great potentials to be developed as therapeutics for inflammatory diseases. PMID- 26132856 TI - Oxysophocarpine Ameliorates Carrageenan-induced Inflammatory Pain via Inhibiting Expressions of Prostaglandin E2 and Cytokines in Mice. AB - Oxysophocarpine is an alkaloid extracted from Sophora alopecuroides. We investigated the analgesic effect of oxysophocarpine on carrageenan-induced inflammatory pain in mice, in order to explore its possible mechanisms. Mouse ear swelling tests and carrageenan-induced paw edema tests were used to investigate the effects of oxysophocarpine on inflammatory pain in mice. Morphological changes on inflamed paw sections were measured by hematoxylin-eosin staining. The mRNA and protein expression of extracellular signal-regulated kinase, phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and prostaglandin E2 were investigated by real-time quantitative polymerase chain reaction, immunohistochemistry, western-blot and enzyme-linked immunosorbent assay. In our results, oxysophocarpine shows a significant anti-inflammatory effect in the mouse ear swelling test. Oxysophocarpine also significantly reduced the paw edema volume and improved mechanical allodynia threshold value on carrageenan-induced inflammatory pain, as well as relieved paw tissues inflammatory damage and reduced the numbers of neutrophils in mice. Oxysophocarpine significantly suppressed over-expression of cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and prostaglandin E2, and inhibited the over phosphorylation of extracellular signal-regulated kinase 1/2. Based on these findings we propose that oxysophocarpine attenuates inflammatory pain by suppressing the levels of phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, prostaglandin E2, tumor necrosis factor alpha, interleukin-1 beta and interleukin-6. PMID- 26132857 TI - Polyphenolic Compounds as Pancreatic Lipase Inhibitors. AB - Obesity and its associated diseases such as diabetes mellitus and coronary heart diseases are a major challenge for our society. An important target for the treatment of obesity includes the development of inhibitors of nutrient digestion and absorption. Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the discovery of potent agents. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion. PMID- 26132858 TI - Natural Products for the Treatment of Type 2 Diabetes Mellitus. AB - Type 2 diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia. High blood sugar can produce long-term complications such as cardiovascular and renal disorders, retinopathy, and poor blood flow. Its development can be prevented or delayed in people with impaired glucose tolerance by implementing lifestyle changes or the use of therapeutic agents. Some of these drugs have been obtained from plants or have a microbial origin, such as galegine isolated from Galega officinalis, which has a great similarity to the antidiabetic drug metformin. Picnogenol, acarbose, miglitol, and voglibose are other antidiabetic products of natural origin. This review compiles the principal articles on medicinal plants used for treating diabetes and its comorbidities, as well as mechanisms of natural products as antidiabetic agents. Inhibition of alpha-glucosidase and alpha-amylase, effects on glucose uptake and glucose transporters, modification of mechanisms mediated by the peroxisome proliferator activated receptor, inhibition of protein tyrosine phosphatase 1B activity, modification of gene expression, and activities of hormones involved in glucose homeostasis such as adiponectin, resistin, and incretin, and reduction of oxidative stress are some of the mechanisms in which natural products are involved. We also review the most relevant clinical trials performed with medicinal plants and natural products such as aloe, banaba, bitter melon, caper, cinnamon, cocoa, coffee, fenugreek, garlic, guava, gymnema, nettle, sage, soybean, green and black tea, turmeric, walnut, and yerba mate. Compounds of high interest as potential antidiabetics are: fukugetin, palmatine, berberine, honokiol, amorfrutins, trigonelline, gymnemic acids, gurmarin, and phlorizin. PMID- 26132859 TI - Messaging to Increase Public Support for Naloxone Distribution Policies in the United States: Results from a Randomized Survey Experiment. AB - BACKGROUND: Barriers to public support for naloxone distribution include lack of knowledge, concerns about potential unintended consequences, and lack of sympathy for people at risk of overdose. METHODS: A randomized survey experiment was conducted with a nationally-representative web-based survey research panel (GfK KnowledgePanel). Participants were randomly assigned to read different messages alone or in combination: 1) factual information about naloxone; 2) pre-emptive refutation of potential concerns about naloxone distribution; and 3) a sympathetic narrative about a mother whose daughter died of an opioid overdose. Participants were then asked if they support or oppose policies related to naloxone distribution. For each policy item, logistic regression models were used to test the effect of each message exposure compared with the no-exposure control group. RESULTS: The final sample consisted of 1,598 participants (completion rate: 72.6%). Factual information and the sympathetic narrative alone each led to higher support for training first responders to use naloxone, providing naloxone to friends and family members of people using opioids, and passing laws to protect people who administer naloxone. Participants receiving the combination of the sympathetic narrative and factual information, compared to factual information alone, were more likely to support all policies: providing naloxone to friends and family members (OR: 2.0 [95% CI: 1.4 to 2.9]), training first responders to use naloxone (OR: 2.0 [95% CI: 1.2 to 3.4]), passing laws to protect people if they administer naloxone (OR: 1.5 [95% CI: 1.04 to 2.2]), and passing laws to protect people if they call for medical help for an overdose (OR: 1.7 [95% CI: 1.2 to 2.5]). CONCLUSIONS: All messages increased public support, but combining factual information and the sympathetic narrative was most effective. Public support for naloxone distribution can be improved through education and sympathetic portrayals of the population who stands to benefit from these policies. PMID- 26132860 TI - KRAS-dependent sorting of miRNA to exosomes. AB - Mutant KRAS colorectal cancer (CRC) cells release protein-laden exosomes that can alter the tumor microenvironment. To test whether exosomal RNAs also contribute to changes in gene expression in recipient cells, and whether mutant KRAS might regulate the composition of secreted microRNAs (miRNAs), we compared small RNAs of cells and matched exosomes from isogenic CRC cell lines differing only in KRAS status. We show that exosomal profiles are distinct from cellular profiles, and mutant exosomes cluster separately from wild-type KRAS exosomes. miR-10b was selectively increased in wild-type exosomes, while miR-100 was increased in mutant exosomes. Neutral sphingomyelinase inhibition caused accumulation of miR 100 only in mutant cells, suggesting KRAS-dependent miRNA export. In Transwell co culture experiments, mutant donor cells conferred miR-100-mediated target repression in wild-type-recipient cells. These findings suggest that extracellular miRNAs can function in target cells and uncover a potential new mode of action for mutant KRAS in CRC. PMID- 26132862 TI - Pain-related psychological distress, self-rated health and significance of neuropathic pain in Danish soldiers injured in Afghanistan. AB - BACKGROUND: Pain and mental health concerns are prevalent among veterans. While the majority of research has focused on chronic pain as an entity, there has been little work directed towards investigating the role of neuropathic pain in relation to psychological comorbidity. As such, we hypothesised that participants with signs of neuropathic pain would report higher levels of psychological distress and diminished self-rated health compared to those without a neuropathic component. METHODS: A retrospective review of standardised questionnaires (PainDETECT Questionnaire, Post-traumatic Stress Disorder Checklist-Civilian, the Hospital Anxiety and Depression Scale, and EuroQOL Visual Analogue Scale) administered to injured soldiers. The participants were classified into three groups according to the PainDETECT questionnaire: non-neuropathic pain, possible neuropathic pain and definite neuropathic pain. RESULTS: Fifty-three participants were included. The Post-traumatic Stress Disorder Checklist-Civilian score was in median (interquartile range) 26 (22-31), the Hospital Anxiety and Depression Scale score was 4 (2-6.5) and 2 (1-5) for anxiety and depression respectively. Evidence of neuropathic pain correlated positively with the Post-traumatic Stress Disorder Checklist-Civilian score (rho = 0.469, P < 0.001) and Hospital Anxiety and Depression Scale subscale for anxiety score (rho = 0.357, P = 0.009), and inversely with the EuroQOL Visual Analogue Scale score (rho = -0.361, P = 0.008). In multivariate regression analyses, the associations remained when adjusting for socio-demographics and clinical characteristics. CONCLUSIONS: The results from the present study suggest that neuropathic pain is related to increased psychological distress and deterioration in self-rated health in injured soldiers. PMID- 26132861 TI - How scent and nectar influence floral antagonists and mutualists. AB - Many plants attract and reward pollinators with floral scents and nectar, respectively, but these traits can also incur fitness costs as they also attract herbivores. This dilemma, common to most flowering plants, could be solved by not producing nectar and/or scent, thereby cheating pollinators. Both nectar and scent are highly variable in native populations of coyote tobacco, Nicotiana attenuata, with some producing no nectar at all, uncorrelated with the tobacco's main floral attractant, benzylacetone. By silencing benzylacetone biosynthesis and nectar production in all combinations by RNAi, we experimentally uncouple these floral rewards/attractrants and measure their costs/benefits in the plant's native habitat and experimental tents. Both scent and nectar increase outcrossing rates for three, separately tested, pollinators and both traits increase oviposition by a hawkmoth herbivore, with nectar being more influential than scent. These results underscore that it makes little sense to study floral traits as if they only mediated pollination services. PMID- 26132863 TI - A study examining senior nursing students' expectations of work and the workforce. AB - AIM: This study explored traditional and accelerated Bachelor of Science nursing students' expectations of nursing work and the workforce. BACKGROUND: Role transition difficulty is blamed for much of the 15-60% newly licensed registered nurse turnover in their first 3 years of employment. METHOD: This qualitative study consisted of 14 focus groups (n = 98) to determine Bachelor of Science nursing students' expectations of work as newly licensed registered nurses. RESULTS: Two overriding themes for accelerated and traditional students emerged: stressors and coping strategies. Students believe four stressors will affect their progression into the newly licensed registered nurse role and have developed coping strategies. CONCLUSION: This study suggests that students have experienced stressors in the clinical environment and anticipate them in the newly licensed registered nurse role. During transition, strategies such as 'fitting in' and 'staying safe' will be employed to ensure work success. IMPLICATIONS FOR NURSING MANAGEMENT: Younger generations value a healthy work life balance and a positive working environment. These nurses will not tolerate positions that do not align with their values. With the aging of citizens in the USA and the predicted nursing shortage, nursing management needs to employ strategies to retain newly licensed registered nurses. PMID- 26132864 TI - Central serous chorioretinopathy: what we have learnt so far. AB - Central serous chorioretinopathy (CSCR) is a common retinal cause of visual loss. The mainstays of management are observation, photodynamic therapy (PDT) and laser procedures. Over the past decade, there has been rapid development in the existing and novel imaging techniques, functional testing and management of CSCR. However, there is no convincing treatment designed for CSCR yet. In recent years, the advances in PDT, with various adjustments in fluence and verteporfin dosage, and the comparisons between different types of PDT for acute and chronic CSCR in recent studies have provided greater insights into the role of PDT in treating CSCR. Novel laser procedures, such as the diode micropulse laser, have shown comparable efficacy to conventional lasers without laser-induced damage. Antivascular endothelial growth factor, which was originally developed for treating cancers, has emerged to be a potentially effective treatment for CSCR. The potential role of mineralocorticoid receptor antagonists in treating CSCR has provided greater understanding of the pathogenesis. Based on the relevant studies, mainly from the past decade, we discuss updates to the management of CSCR according to the risk factor modifications, pharmacological interventions, PDT and laser procedures and concluded that PDT is the current best option for CSCR. PMID- 26132865 TI - King v. Burwell--ACA Armageddon Averted. PMID- 26132867 TI - Composition-dependent electrocatalytic activity of palladium-iridium binary alloy nanoparticles supported on the multiwalled carbon nanotubes for the electro oxidation of formic acid. AB - Surface-functionalized multiwalled carbon nanotubes (MWCNTs) supported Pd100-xIrx binary alloy nanoparticles (Pd100-xIrx/MWCNT) with tunable Pd/Ir atomic ratios were synthesized by a thermolytic process at varied ratios of bis(acetylacetonate) palladium(II) and iridium(III) 2,4-pentanedionate precursors and then applied as the electrocatalyst for the formic acid electro-oxidation. The X-ray diffraction pattern (XRD) and transmission electron microscope (TEM) analysis showed that the Pd100-xIrx alloy nanoparticles with the average size of 6.2 nm were uniformly dispersed on the MWCNTs and exhibited a single solid solution phase with a face-centered cubic structure. The electrocatalytic properties were evaluated through the cyclic voltammetry and chronoamperometry tests, and the results indicated that both the activity and stability of Pd100 xIrx/MWCNT were strongly dependent on the Pd/Ir atomic ratios: the best electrocatalytic performance in terms of onset potential, current density, and stability against CO poisoning was obtained for the Pd79Ir21/MWCNT. Moreover, compared with pure Pd nanoparticles supported on MWCNTs (Pd/MWCNT), the Pd79Ir21/MWCNT exhibited enhanced steady-state current density and higher stability, as well as maintained excellent electrocatalytic activity in high concentrated formic acid solution, which was attributed to the bifunctional effect through alloying Pd with transition metal. PMID- 26132866 TI - Effects of Simulated Rare Earth Recycling Wastewaters on Biological Nitrification. AB - Increasing rare earth element (REE) supplies by recycling and expanded ore processing will result in generation of new wastewaters. In some cases, disposal to a sewage treatment plant may be favored, but plant performance must be maintained. To assess the potential effects of such wastewaters on biological treatment, model nitrifying organisms Nitrosomonas europaea and Nitrobacter winogradskyi were exposed to simulated wastewaters containing varying levels of yttrium or europium (10, 50, and 100 ppm), and the extractant tributyl phosphate (TBP, at 0.1 g/L). Y and Eu additions at 50 and 100 ppm inhibited N. europaea, even when virtually all of the REE was insoluble. Provision of TBP with Eu increased N. europaea inhibition, although TBP alone did not substantially alter activity. For N. winogradskyi cultures, Eu or Y additions at all tested levels induced significant inhibition, and nitrification shut down completely with TBP addition. REE solubility was calculated using the previously developed MSE (Mixed Solvent Electrolyte) thermodynamic model. The model calculations reveal a strong pH dependence of solubility, typically controlled by the precipitation of REE hydroxides but also likely affected by the formation of unknown phosphate phases, which determined aqueous concentrations experienced by the microorganisms. PMID- 26132878 TI - Modeling the Photoelectron Spectra of MoNbO2(-) Accounting for Spin Contamination in Density Functional Theory. AB - Spin contamination in density functional studies has been identified as a cause of discrepancies between theoretical and experimental spectra of metal oxide clusters such as MoNbO2. We perform calculations to simulate the photoelectron spectra of the MoNbO2 anion using broken-symmetry density functional theory incorporating recently developed approximate projection methods. These calculations are able to account for the presence of contaminating spin states at single-reference computational cost. Results using these new tools demonstrate the significant effect of spin-contamination on geometries and force constants and show that the related errors in simulated spectra may be largely overcome by using an approximate projection model. PMID- 26132879 TI - Copper-64 Labeled Macrobicyclic Sarcophagine Coupled to a GRP Receptor Antagonist Shows Great Promise for PET Imaging of Prostate Cancer. AB - The gastrin-releasing peptide receptor (GRPr) is an important molecular target for the visualization and therapy of tumors and can be targeted with radiolabeled bombesin derivatives. The present study aims to develop statine-based bombesin receptor antagonists suitable for labeling with 64Cu for imaging by positron emission tomography (PET). The potent GRPr antagonist D-Phe-Gln-Trp-Ala-Val-Gly His-Sta-Leu-NH2 was conjugated to the sarcophagine (3,6,10,13,16,19 hexaazabicyclo[6.6.6] icosane=Sar) derivative 5-(8-methyl-3,6,10,13,16,19-hexaaza bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar) via PEG4 (LE1) and PEG2 (LE2) spacers and radiolabeled with 64Cu2+ with >95% yield and specific activities of about 100 MBq/nmol. Both Cu(II) conjugates have high affinity for GRPr (IC50: natCu-LE1, 1.4+/-0.1 nM; natCu-LE2, 3.8+/-0.6 nM). The antagonistic properties of both conjugates were confirmed by Ca2+-flux measurements. Biodistribution studies of Cu-64-LE1 exhibited specific targeting of the tumor (19.6+/-4.7% IA/g at 1 h p.i.) and GRPr-positive organs. Biodistribution and PET images at 4 and 24 h postinjection showed increasing tumor-to-background ratios with time. This was illustrated by the acquisition of PET images showing high tumor-to-normal tissue contrast. This study demonstrates the high affinity of the MeCOSar-PEGx-bombesin conjugates to GRPr. The stability of 64Cu complexes of MeCOSar, the long half-life of 64Cu, and the suitable biodistribution profile of the 64Cu-labeled peptides lead to PET images of high contrast suitable for potential translation into the clinic. PMID- 26132881 TI - Self-propelled micromotors based on Au-mesoporous silica nanorods. AB - Here, a chemical powered micromotor from the assembly of Au-SiO2 nanorods is presented. This new micromotor can be propelled efficiently by hydrogen bubbles generated from a hydrolysis reaction of aqueous NaBH4 and KBH4 and by oxygen bubbles produced by decomposition of H2O2. The monodisperse Au nanoparticles in mesoporous silica particles could catalyze the decomposition of two different kinds of fuels and produce bubbles. High speeds of 80 MUm s(-1) and recycles of more than 30 times are achieved in both NaBH4 and H2O2 media. Locomotion and rolling forms of movement were found. The locomotion forms can be obtained in a larger proportion by patterning the Au-SiO2 nanorods and a PDMS membrane. These micromotors that use multiple fuel sources to power them offer a broader scope of preparation and show considerable promise for diverse applications of nanomotors in different chemical environments. PMID- 26132880 TI - Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis. AB - Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS QMA to quantify skewed XCI in two applications with diagnostic utility. PMID- 26132882 TI - Cyclophilin A/Cluster of Differentiation 147 Interactions Participate in Early Brain Injury After Subarachnoid Hemorrhage in Rats. AB - OBJECTIVES: Cyclophilin A has been found to be involved in many inflammatory diseases via its receptor, cluster of differentiation 147 (CD147). This study was designed to estimate the potential role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury. DESIGN: Controlled in vivo laboratory study. SETTING: Animal research laboratory. SUBJECTS: Two hundred ninety adult male Sprague-Dawley rats weighing 300-350 g. INTERVENTIONS: A prechiasmatic cistern single-injection model was used to produce experimental subarachnoid hemorrhage in Sprague-Dawley rats. The expressions of cyclophilin A and CD147, the interaction between cyclophilin A and CD147, and the secretion of cyclophilin A were assessed using immunofluorescence staining, Western blot analysis, and coimmunoprecipitation analysis. Down-regulation of cyclophilin A expression by small interfering RNA was performed, and recombinant human cyclophilin A and monoclonal antibody of CD147 were exploited to study the role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury. MEASUREMENTS AND MAIN RESULTS: The expressions of cyclophilin A and CD147 in neurons were higher than that of the sham group and peaked at 24 hours after subarachnoid hemorrhage. Compared with sham group, subarachnoid hemorrhage was found to increase the secretion of cyclophilin A and the interaction between cyclophilin A and CD147. Cyclophilin A small interfering RNA and anti-CD147 treatments were found to ameliorate subarachnoid hemorrhage-induced early brain injury, including cortical apoptosis and necrosis, brain edema, blood-brain barrier damage, and neurobehavioral deficits. Cyclophilin A small interfering RNA and anti-CD147 treatments also decreased the phosphorylation of extracellular signal-regulated protein kinase 1/2, the protein levels of p53 and caspase-3, and the level of active nuclear factor-kappaB. Finally, recombinant human cyclophilin A treatment resulted in an opposite effect, which was inhibited by anti-CD147 treatment. CONCLUSIONS: Cyclophilin A/CD147 interactions may participate in subarachnoid hemorrhage-induced early brain injury via increasing neuronal apoptosis pathway, at least partly through the ERK1/2-nuclear factor-kappaB pathway. Cyclophilin A/CD147 may be a suitable therapeutic target for subarachnoid hemorrhage. PMID- 26132883 TI - Self-Perceptions of Sexual Attractiveness: Satisfaction With Physical Appearance is Not of Primary Importance Across Gender and Sexual Orientation. AB - Research on self-perceived sexual attractiveness has predominantly focused on the importance of physical appearance, overlooking nonphysical traits that may contribute to these self-perceptions. The present study examined and compared the importance of a variety of traits for self-perceived sexual attractiveness. Self identified heterosexual, gay, and bisexual men (N = 1,801) and heterosexual, lesbian, and bisexual women (N = 1,092) completed an online questionnaire examining self-perceived sexual attractiveness, body esteem, sexual esteem, adherence to gender norms, and sexual experience. Body esteem and sexual esteem were significant predictors of self-perceived sexual attractiveness, regardless of gender and sexual orientation. Adhering to a masculine gender norm was a significant predictor among all groups (to varying extents) but heterosexual women. Adhering to a feminine gender norm was a significant predictor among heterosexual men and bisexual women. Finally, sexual experience was a significant predictor for all men and bisexual women. Furthermore, while body esteem was a predictor across all groups, for most individuals it did not appear to be of primary importance, with either sexual esteem or masculinity proving to be of greater importance. These findings suggest the need to consider traits related to both physical and nonphysical factors for improving an individual's self perceived sexual attractiveness. PMID- 26132884 TI - The relationship between phonological short-term memory, receptive vocabulary, and fast mapping in children with specific language impairment. AB - BACKGROUND: Children with specific language impairment (SLI) often experience word-learning difficulties, which are suggested to originate in the early stage of word learning: fast mapping. Some previous research indicates significantly poorer fast mapping capabilities in children with SLI compared with typically developing (TD) counterparts, with a range of methodological factors impacting on the consistency of this finding. Research has explored key issues that might underlie fast mapping difficulties in children with SLI, with strong theoretical support but little empirical evidence for the role of phonological short-term memory (STM). Additionally, further research is required to explore the influence of receptive vocabulary on fast mapping capabilities. Understanding the factors associated with fast mapping difficulties that are experienced by children with SLI may lead to greater theoretically driven word-learning intervention. AIMS: To investigate whether children with SLI demonstrate significant difficulties with fast mapping, and to explore the related factors. It was hypothesized that children with SLI would score significantly lower on a fast mapping production task compared with TD children, and that phonological STM and receptive vocabulary would significantly predict fast mapping production scores in both groups of children. METHODS & PROCEDURES: Twenty-three children with SLI (mean = 64.39 months, SD = 4.10 months) and 26 TD children (mean = 65.92 months, SD = 2.98) were recruited from specialist language and mainstream schools. All participants took part in a unique, interactive fast-mapping task whereby nine novel objects with non-word labels were presented and production accuracy was assessed. A non-word repetition test and the Peabody Picture Vocabulary Test Fourth Edition (PPVT-IV) were also administered as measures of phonological STM capacity and receptive vocabulary, respectively. OUTCOMES & RESULTS: Results of the fast-mapping task indicated that children with SLI had significantly poorer fast mapping production scores than TD children. Scores from the non-word repetition task were also significantly lower for the SLI group, revealing reduced phonological STM capacity. Phonological STM capacity and receptive vocabulary emerged as significant predictors of fast mapping performance when the group data were combined in a multiple regression analysis. CONCLUSIONS & IMPLICATIONS: These results suggest that the word-learning difficulties experienced by children with SLI may originate at the fast mapping stage, and that phonological STM and receptive vocabulary significantly predict fast mapping ability. These findings contribute to the theoretical understanding of word learning difficulties in children with SLI and may inform lexical learning intervention. PMID- 26132885 TI - The Effects of Alveolar Ridge Preservation: A Meta-Analysis. AB - PURPOSE: The aim of this article was to analyze the horizontal, vertical, and histological effects of alveolar ridge preservation (ARP) versus the ones of unassisted socket healing, in the format of an up-to-date review and meta analysis. MATERIALS AND METHODS: An extensive electronic search in the electronic databases of the National Library of Medicine was conducted for articles published up to June 2014 to identify literature presenting data on the topic of ARP. Only randomized controlled trials, controlled clinical trials, and prospective trials were included for meta-analysis. RESULTS: After screening 903 abstracts from the electronic database, we included 64 studies in qualitative and 18 in quantitative synthesis. Quality assessment characterized a medium risk of bias for the included literature. The meta-analysis showed a mean difference between test and control groups of approximately 1.31 to 1.54 mm in bucco-oral bone width and 0.91 to 1.12 mm in bone height. Additionally, the intergroup difference in percentage of vital bone was assessed to be inconclusive across the included studies. Implants could be inserted into the determined position without further augmentation in 90.1% of the experimental sites, while this was the case in only 79.2% of the control sockets. CONCLUSIONS: Resorption of the alveolar ridge cannot be totally stopped by ARP, while it still can be prevented compared with unassisted healing. No reliable predictions on the histological effects could be made due to limited data. Further on, no recommendation for a specific technique of ARP could be made. In conclusion, there is still need for ongoing research on the topic, even though the lower percentage of implant sites that needed additional augmentation in test sockets seemed to bring a patient benefit. PMID- 26132886 TI - Against 'Saving Lives': Equal Concern and Differential Impact. AB - Bioethicists often present 'saving lives' as a goal distinct from, and competing with, that of extending lives by as much as possible. I argue that this usage of the term is misleading, and provides unwarranted rhetorical support for neglecting the magnitudes of the harms and benefits at stake in medical allocation decisions, often to the detriment of the young. Equal concern for all persons requires weighting equal interests equally, but not all individuals have an equal interest in 'life-saving' treatment. PMID- 26132887 TI - Effects of Online Self-Regulation Activities on Physical Activity Among Pregnant and Early Postpartum Women. AB - Physical and psychological changes that occur during pregnancy present a unique challenge for women's physical activity. Using a theory-based prospective design, this study examines the effects of pregnant women's (a) physical activity cognitions (self-efficacy, outcome expectancy, and safety beliefs) and (b) online self-regulation activities (goal-setting and self-monitoring) on subsequent changes in their physical activity intentions and behavior during pregnancy and immediately postpartum. The authors used data from three panel surveys administered to pregnant women enrolled in a web-based intervention to promote healthy pregnancy and postpartum weight, as well as log data on their use of self regulatory features on the intervention website. Perceived self-efficacy and perceived safety of physical activity in pregnancy enhanced subsequent intentions to be physically active. Repeated goal-setting and monitoring of those goals helped to maintain positive intentions during pregnancy, but only repeated self monitoring transferred positive intentions into actual behavior. Theoretically, this study offers a better understanding of the roles of self-regulation activities in the processes of goal-striving. The authors also discuss practical implications for encouraging physical activity among pregnant and early postpartum women. PMID- 26132889 TI - Improved Expression and Characterization of a Multidomain Xylanase from Thermoanaerobacterium aotearoense SCUT27 in Bacillus subtilis. AB - A xylanase gene was cloned and characterized from Thermoanerobacterium aotearoense SCUT27, which was attested to consist of a signal peptide, one glycoside hydrolase family 10 domain, four carbohydrate binding modules, and three surface layer homology domains. The change of expression host from Escherichia coli to Bacillus subtilis resulted in a 4.1-fold increase of specific activity for the truncated XynADeltaSLH. Five different versions of secretion signals in B. subtilis indicated that it was preferably routed via a Sec dependent pathway. Purified XynADeltaSLH showed a high activity of 379.8 U/mg on beechwood xylan. XynADeltaSLH was optimally active at 80 degrees C, pH 6.5. Thin layer chromatography results showed that xylobiose and the presumed methylglucuronoxylotriose (MeGlcAXyl3) were the main products liberated from beechwood xylan catalyzed by the recombinant xylanase. All of the results suggest that XynADeltaSLH is a suitable candidate for generating xylooligosaccharides from cellulosic materials for industrial uses. PMID- 26132888 TI - Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins. AB - Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi product analysis by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented. PMID- 26132891 TI - Propagation Behaviors of an Acid Wavefront Through a Microchannel Junction. AB - Waves in reaction-diffusion systems yield a wealth of dynamic self-assembling phenomena in nature. Recent studies have been devoted to utilizing these active waves in conjunction with microscale technology. To provide a compass for controlling reaction-diffusion waves in microspaces, we have investigated the propagation behavior of one specific variety of the reaction-diffusion wave: an acid wave that utilizes an autocatalytic proton-production reaction. Furthermore, the acid wave that we have investigated occurs in a microchannel with a junction connecting circular and straight regions. The obtained results were compared with a neutralization wave that involves only a neutralization reaction. The acid wave was ignited by the addition of the appropriate amount of H2SO4 into the circular region that was filled with a substrate solution, where proton-consuming and proton-producing reactions followed a rapid neutralization reaction. At this stage, the wave penetrated and propagated into the channel region. Comparison between the acid and the neutralization waves clarified that the acid wave required a minimum threshold of H2SO4 concentration in order to be ignited and that the propagation of the acid wave was temporarily delayed because of the presence of intermediate chemical reaction steps. Furthermore, the propagation dynamics was found to be tuned through the configuration of the microchannel. The importance of microchannel configuration, especially for systems with a junction connecting different shapes, is discussed in terms of Fick's law and in terms of the proton flux from the circular to the straight regions. PMID- 26132890 TI - Trabecular Meshwork Response to Pressure Elevation in the Living Human Eye. AB - The mechanical characteristics of the trabecular meshwork (TM) are linked to outflow resistance and intraocular pressure (IOP) regulation. The rationale behind this technique is the direct observation of the mechanical response of the TM to acute IOP elevation. Prior to scanning, IOP is measured at baseline and during IOP elevation. The limbus is scanned by spectral-domain optical coherence tomography at baseline and during IOP elevation (ophthalmodynamometer (ODM) applied at 30 g force). Scans are processed to enhance visualization of the aqueous humor outflow pathway using ImageJ. Vascular landmarks are used to identify corresponding locations in baseline and IOP elevation scan volumes. Schlemm canal (SC) cross-sectional area (SC-CSA) and SC length from anterior to posterior along its long axis are measured manually at 10 locations within a 1 mm segment of SC. Mean inner to outer wall distance (short axis length) is calculated as the area of SC divided by its long axis length. To examine the contribution of adjacent tissues to the effect IOP elevations, measurements are repeated without and with smooth muscle relaxation with instillation of tropicamide. TM migration into SC is resisted by TM stiffness, but is enhanced by the support of its attachment to adjacent smooth muscle within the ciliary body. This technique is the first to measure the living human TM response to pressure elevation in situ under physiological conditions within the human eye. PMID- 26132892 TI - Use of the Parell Frontal Sinus T-Stent to prevent external auditory canal stenosis. PMID- 26132893 TI - Nail bed reconstruction with local flaps after full-thickness chemical burn. PMID- 26132894 TI - Keloid removal by shave excision with adjuvant external beam radiation therapy. PMID- 26132895 TI - A Sucrose Mouth Rinse Does Not Improve 1-hr Cycle Time Trial Performance When Performed in the Fasted or Fed State. AB - Carbohydrate mouth rinsing during exercise has been suggested to enhance performance of short (45-60 min) bouts of high-intensity (>75% VO2peak) exercise. Recent studies indicate that this performance enhancing effect may be dependent on the prandial state of the athlete. The purpose of this study was to define the impact of a carbohydrate mouth rinse on ~1-hr time trial performance in both the fasted and fed states. Using a double-blind, crossover design, 14 trained male cyclists (27 +/- 6 years; 5.0 +/- 0.5 W . kg(-1)) were selected to perform 4 time trials of ~1 hr (1,032 +/- 127 kJ) on a cycle ergometer while rinsing their mouths with a 6.4% sucrose solution (SUC) or a noncaloric sweetened placebo (PLA) for 5 s at the start and at every 12.5% of their set amount of work completed. Two trials were performed in an overnight fasted state and two trials were performed 2 h after consuming a standardized breakfast. Performance time did not differ between any of the trials (fasted-PLA: 68.6 +/- 7.2; fasted-SUC: 69.6 +/- 7.5; fed-PLA: 67.6 +/- 6.6; and fed-SUC: 69.0 +/- 6.3 min; Prandial State * Mouth Rinse Solution p = .839; main effect prandial state p = .095; main effect mouth rinse solution p = .277). In line, mean power output and heart rate during exercise did not differ between trials. In conclusion, a sucrose mouth rinse does not improve ~1-hr time trial performance in well-trained cyclists when performed in either the fasted or the fed state. PMID- 26132896 TI - Reorganization of corticospinal tract fibers after spinal cord injury in adult macaques. AB - Previous studies have shown that sprouting of corticospinal tract (CST) fibers after spinal cord injury (SCI) contributes to recovery of motor functions. However, the neuroanatomical mechanism underlying the functional recovery through sprouting CST fibers remains unclear. Here we investigated the pattern of reorganization of CST fibers below the lesion site after SCI in adult macaques. Unilateral lesions were made at the level between the C7 and the C8 segment. The extent of spontaneous recovery of manual dexterity was assessed with a reaching/grasping task. The impaired dexterous manual movements were gradually recovered after SCI. When anterograde tract tracing with biotinylated dextran amine was performed to identify the intraspinal reinnervation of sprouting CST fibers, it was found that the laminar distribution of CST fibers was changed. The sprouting CST fibers extended preferentially into lamia IX where the spinal motor neuron pool was located, to innervate the motor neurons directly. Instead, few, if any, CST fibers were distributed in the dorsal laminae. The present results indicate that CST fibers below the lesion site after SCI in macaques are reorganized in conjunction with the recovery of dexterous manual movements. PMID- 26132898 TI - Congenital analbuminaemia diagnosed in adulthood in an Australian family. PMID- 26132899 TI - Laboratory testing in management of patients with suspected Ebolavirus disease: infection control and safety. AB - If routine laboratory safety precautions are followed, the risk of laboratory acquired infection from handling specimens from patients with Ebolavirus disease (EVD) is very low, especially in the early 'dry' stage of disease. In Australia, border screening to identify travellers returning from EVD-affected west African countries during the 2014-2015 outbreak has made it unlikely that specimens from patients with unrecognised EVD would be sent to a routine diagnostic laboratory. Australian public health and diagnostic laboratories associated with hospitals designated for the care of patients with EVD have developed stringent safety precautions for EVD diagnostic and other tests likely to be required for supportive care of the sickest (and most infectious) patients with EVD, including as wide a range of point-of-care tests as possible. However, it is important that the stringent requirements for packaging, transport and testing of specimens that might contain Ebolavirus--which is a tier 1 security sensitive biology agent--do not delay the diagnosis and appropriate management of other potentially serious but treatable infectious diseases, which are far more likely causes of a febrile illness in people returning from west Africa. If necessary, urgent haematology, biochemistry and microbiological tests can be performed safely, whilst awaiting the results of EVD tests, in a PC-2 laboratory with appropriate precautions including: use of recommended personal protective equipment (PPE) for laboratory staff; handling any unsealed specimens in a class 1 or II biosafety cabinet; using only centrifuges with sealed rotors; and safe disposal or decontamination of all used equipment and laboratory waste. PMID- 26132900 TI - Extracorporeal Life Support. PMID- 26132897 TI - High-throughput RNA sequencing reveals structural differences of orthologous brain-expressed genes between western lowland gorillas and humans. AB - The human brain and human cognitive abilities are strikingly different from those of other great apes despite relatively modest genome sequence divergence. However, little is presently known about the interspecies divergence in gene structure and transcription that might contribute to these phenotypic differences. To date, most comparative studies of gene structure in the brain have examined humans, chimpanzees, and macaque monkeys. To add to this body of knowledge, we analyze here the brain transcriptome of the western lowland gorilla (Gorilla gorilla gorilla), an African great ape species that is phylogenetically closely related to humans, but with a brain that is approximately one-third the size. Manual transcriptome curation from a sample of the planum temporale region of the neocortex revealed 12 protein-coding genes and one noncoding-RNA gene with exons in the gorilla unmatched by public transcriptome data from the orthologous human loci. These interspecies gene structure differences accounted for a total of 134 amino acids in proteins found in the gorilla that were absent from protein products of the orthologous human genes. Proteins varying in structure between human and gorilla were involved in immunity and energy metabolism, suggesting their relevance to phenotypic differences. This gorilla neocortical transcriptome comprises an empirical, not homology- or prediction-driven, resource for orthologous gene comparisons between human and gorilla. These findings provide a unique repository of the sequences and structures of thousands of genes transcribed in the gorilla brain, pointing to candidate genes that may contribute to the traits distinguishing humans from other closely related great apes. PMID- 26132901 TI - Interleukin-10 is a critical regulator of white matter lesion containment following viral induced demyelination. AB - Neurotropic coronavirus induces an acute encephalomyelitis accompanied by focal areas of demyelination distributed randomly along the spinal column. The initial areas of demyelination increase only slightly after the control of infection. These circumscribed focal lesions are characterized by axonal sparing, myelin ingestion by macrophage/microglia, and glial scars associated with hypertrophic astrocytes, which proliferate at the lesion border. Accelerated virus control in mice lacking the anti-inflammatory cytokine IL-10 was associated with limited initial demyelination, but low viral mRNA persistence similar to WT mice and declining antiviral cellular immunity. Nevertheless, lesions exhibited sustained expansion providing a model of dysregulated white matter injury temporally remote from the acute CNS insult. Expanding lesions in the absence of IL-10 are characterized by sustained microglial activation and partial loss of macrophage/microglia exhibiting an acquired deactivation phenotype. Furthermore, IL-10 deficiency impaired astrocyte organization into mesh like structures at the lesion borders, but did not prevent astrocyte hypertrophy. The formation of discrete foci of demyelination in IL-10 sufficient mice correlated with IL-10 receptor expression exclusively on astrocytes in areas of demyelination suggesting a critical role for IL-10 signaling to astrocytes in limiting expansion of initial areas of white matter damage. GLIA 2015;63:2106-2120. PMID- 26132902 TI - Microbial diversity in shallow-water hydrothermal sediments of Kueishan Island, Taiwan as revealed by pyrosequencing. AB - Kueishan Island is a young volcanic island in the southernmost edge of the Okinawa Trough in the northeastern part of Taiwan. A cluster of hydrothermal vents is located off the southeastern tip of the Island at water depths between 10 and 80 m. This paper presents the results of the first study on the microbial communities in bottom sediments collected from the shallow-water hydrothermal vents of Kueishan Island. Small-subunit ribosomal RNA gene-based high-throughput 454 pyrosequencing was used to characterize the assemblages of bacteria, archaea, and small eukaryotes in sediment samples collected at various distances from the hydrothermal vents. Sediment from the vent area contained the highest diversity of archaea and the lowest diversity of bacteria and small eukaryotes. Epsilonproteobacteria were the most abundant group in the vent sediment, but their abundance decreased with increasing distance from the vent area. Most Epsilonproteobacteria belonged to the mesophilic chemolithoautotrophic genera Sulfurovum and Sulfurimonas. Recent reports on these two genera have come from deep-sea hydrothermal vents. Conversely, the relative contribution of Gammaproteobacteria to the bacterial community increased with increasing distance from the vent area. Our study revealed the contrasting effects of venting on the benthic bacterial and archaeal communities, and showed that the sediments of the shallow-waters hydrothermal vents were dominated by chemoautotrophic bacteria. The present work broadens our knowledge on microbial diversity in shallow-water hydrothermal vent habitats. PMID- 26132903 TI - A Multi-Target Approach toward the Development of Novel Candidates for Antidermatophytic Activity: Ultrastructural Evidence on alpha-Bisabolol-Treated Microsporum gypseum. AB - Multi-target strategies are directed toward targets that are unrelated (or distantly related) and can create opportunities to address different pathologies. The antidermatophytic activities of nine natural skin lighteners: alpha bisabolol, kojic acid, beta-arbutin, azelaic acid, hydroquinone, nicotinamide, glycine, glutathione and ascorbyl tetraisopalmitate, were evaluated, in comparison with the known antifungal drug fluconazole, on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Nannizzia cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Arthroderma gypseum, Trichophyton rubrum and Trichophyton tonsurans. alpha-Bisabolol showed the best antifungal activity against all fungi and in particular; against M. gypseum. Further investigations were conducted on this fungus to evaluate the inhibition of spore germination and morphological changes induced by alpha-bisabolol by TEM. PMID- 26132904 TI - Anemarrhena asphodeloides Non-Steroidal Saponin Components Alter the Pharmacokinetic Profile of Its Steroidal Saponins in Rat. AB - A rapid, selective and sensitive UPLC-MS/MS assay was established to determine the plasma concentrations of four steroidal saponins. Sprague-Dawley rats were allocated to four groups which were orally administered Anemarrhena asphodeloides extracts (ASE), ASE combined with macromolecular fraction (ASE-MF), ASE combined with small molecule fraction (ASE-SF) and ASE combined with small molecule and macromolecular fraction (ASE-SF-MF) containing approximately the same dose of ASE. At different time points, the concentration of timosaponin BII, anemarsaponin BIII, timosaponin AIII and timosaponin E1 in rat plasma were determined and main pharmacokinetic parameters including Cmax, Tmax, T1/2, AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student's t-test with p < 0.05 as the level of significance. MF had no effect on the pharmacokinetic behaviors and parameters of four steroidal saponins. It was found that Cmax and AUC of four steroidal saponins in group ASE-SF and ASE-SF-MF, were significantly increased compared with those in group ASE. These results indicate that SF in A. asphodeloides extracts could increase the absorption and improve the bioavailability of the steroidal saponins. PMID- 26132905 TI - Inhibition of Tapeworm Thioredoxin and Glutathione Pathways by an Oxadiazole N Oxide Leads to Reduced Mesocestoides vogae Infection Burden in Mice. AB - Parasitic flatworms cause serious infectious diseases that affect humans and livestock in vast regions of the world, yet there are few effective drugs to treat them. Thioredoxin glutathione reductase (TGR) is an essential enzyme for redox homeostasis in flatworm parasites and a promising pharmacological target. We purified to homogeneity and characterized the TGR from the tapeworm Mesocestoides vogae (syn. M. corti). This purification revealed absence of conventional TR and GR. The glutathione reductase activity of the purified TGR exhibits a hysteretic behavior typical of flatworm TGRs. Consistently, M. vogae genome analysis revealed the presence of a selenocysteine-containing TGR and absence of conventional TR and GR. M. vogae thioredoxin and glutathione reductase activities were inhibited by 3,4-bis(phenylsulfonyl)-1,2,5-oxadiazole N2-oxide (VL16E), an oxadiazole N-oxide previously identified as an inhibitor of fluke and tapeworm TGRs. Finally, we show that mice experimentally infected with M. vogae tetrathyridia and treated with either praziquantel, the reference drug for flatworm infections, or VL16E exhibited a 28% reduction of intraperitoneal larvae numbers compared to vehicle treated mice. Our results show that oxadiazole N oxide is a promising chemotype in vivo and highlights the convenience of M. vogae as a model for rapid assessment of tapeworm infections in vivo. PMID- 26132906 TI - The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene beta-Caryophyllene from the Essential Oil of Aquilaria crassna. AB - The present study reports a bioassay-guided isolation of beta-caryophyllene from the essential oil of Aquilaria crassna. The structure of beta-caryophyllene was confirmed using FT-IR, NMR and MS. The antimicrobial effect of beta-caryophyllene was examined using human pathogenic bacterial and fungal strains. Its anti oxidant properties were evaluated by DPPH and FRAP scavenging assays. The cytotoxicity of beta-caryophyllene was tested against seven human cancer cell lines. The corresponding selectivity index was determined by testing its cytotoxicity on normal cells. The effects of beta-caryophyllene were studied on a series of in vitro antitumor-promoting assays using colon cancer cells. Results showed that beta-caryophyllene demonstrated selective antibacterial activity against S. aureus (MIC 3 +/- 1.0 uM) and more pronounced anti-fungal activity than kanamycin. beta-Caryophyllene also displayed strong antioxidant effects. Additionally, beta-caryophyllene exhibited selective anti-proliferative effects against colorectal cancer cells (IC50 19 uM). The results also showed that beta caryophyllene induces apoptosis via nuclear condensation and fragmentation pathways including disruption of mitochondrial membrane potential. Further, beta caryophyllene demonstrated potent inhibition against clonogenicity, migration, invasion and spheroid formation in colon cancer cells. These results prompt us to state that beta-caryophyllene is the active principle responsible for the selective anticancer and antimicrobial activities of A. crassnia. beta Caryophyllene has great potential to be further developed as a promising chemotherapeutic agent against colorectal malignancies. PMID- 26132907 TI - The Curcumin Analogue 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one Induces Apoptosis and Downregulates E6 and E7 Oncogene Expression in HPV16 and HPV18 Infected Cervical Cancer Cells. AB - In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5 bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17, 1.03 +/- 0.5 MUM; 2.6 +/- 0.9 MUM) and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13, 2.8 +/- 0.4; 6.7 +/- 2.4 MUM) in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cancer. PMID- 26132908 TI - Synthesis, Antiviral Bioactivity of Novel 4-Thioquinazoline Derivatives Containing Chalcone Moiety. AB - A series of novel 4-thioquinazoline derivatives containing chalcone moiety were designed, synthesized and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds exhibited moderate to good anti-TMV activity. In particular, compounds M2 and M6 possessed appreciable protection activities against TMV in vivo, with 50% effective concentration (EC50) values of 138.1 and 154.8 MUg/mL, respectively, which were superior to that of Ribavirin (436.0 MUg/mL). The results indicated that chalcone derivatives containing 4-thioquinazoline moiety could effectively control TMV. Meanwhile, the structure-activity relationship (SAR) of the target compounds, studied using the three-dimensional quantitative structure-activity relationship (3D-QSAR) method of comparative molecular field analysis (CoMFA) based on the protection activities against TMV, demonstrated that the CoMFA model exhibited good predictive ability with the cross-validated q2 and non-cross-validated r2 values of 0.674 and 0.993, respectively. Meanwhile, the microscale thermophoresis (MST) experimental showed that the compound M6 may interaction with the tobacco mosaic virus coat protein (TMV CP). PMID- 26132909 TI - Investigations on Synperiplanar and Antiperiplanar Isomers of Losartan: Theoretical and Experimental NMR Studies. AB - Losartan inhibits the renin-angiotensin-aldosterone system by blocking the angiotensin II receptor. It is commonly used in cardiovascular diseases, such as hypertension. Several publications applied the ab initio and density functional theory methods to investigate the molecule of losartan. Only in one of them were the nuclear magnetic resonance spectra calculations carried out, and their results were correlated with the experimental values. The authors focused their attention on calculations of the anion form of losartan, taking into consideration both its synperiplanar and antiperiplanar configurations. Coefficients of determination and mean absolute deviation parameters were calculated for the experimental and calculated chemical shifts for every used basis set. They showed a noticeably stronger correlation for the anti-isomers than for the syn-isomers. Moreover, the solvation model increased the value of this parameter. The results of calculations confirmed that an anti-conformation of the analyte seems to be the preferred one, and such an orientation might be most potent within the receptor cavity, which is in agreement with the results of previous studies. PMID- 26132910 TI - Culture Condition Optimization and Pilot Scale Production of the M12 Metalloprotease Myroilysin Produced by the Deep-Sea Bacterium Myroides profundi D25. AB - The protease myroilysin is the most abundant protease secreted by marine sedimental bacterium Myroides profundi D25. As a novel elastase of the M12 family, myroilysin has high elastin-degrading activity and strong collagen swelling ability, suggesting its promising biotechnological potential. Because myroilysin cannot be maturely expressed in Escherichia coli, it is important to be able to improve the production of myroilysin in the wild strain D25. We optimized the culture conditions of strain D25 for protease production by using single factor experiments. Under the optimized conditions, the protease activity of strain D25 reached 1137 +/- 53.29 U/mL, i.e., 174% of that before optimization (652 +/- 23.78 U/mL). We then conducted small scale fermentations of D25 in a 7.5 L fermentor. The protease activity of strain D25 in small scale fermentations reached 1546.4 +/- 82.65 U/mL after parameter optimization. Based on the small scale fermentation results, we further conducted pilot scale fermentations of D25 in a 200 L fermentor, in which the protease production of D25 reached approximately 1100 U/mL. These results indicate that we successfully set up the small and pilot scale fermentation processes of strain D25 for myroilysin production, which should be helpful for the industrial production of myroilysin and the development of its biotechnological potential. PMID- 26132911 TI - Ambiphilic Frustrated Lewis Pair Exhibiting High Robustness and Reversible Water Activation: Towards the Metal-Free Hydrogenation of Carbon Dioxide. AB - The synthesis and structural characterization of a phenylene-bridged Frustrated Lewis Pair (FLP) having a 2,2,6,6-tetramethylpiperidine (TMP) as the Lewis base and a 9-borabicyclo[3.3.1]nonane (BBN) as the Lewis acid is reported. This FLP exhibits unique robustness towards the products of carbon dioxide hydrogenation. The compound shows reversible splitting of water, formic acid and methanol while no reaction is observed in the presence of excess formaldehyde. The molecule is incredibly robust, showing little sign of degradation after heating at 80 degrees C in benzene with 10 equiv. of formic acid for 24 h. The robustness of the system could be exploited in the design of metal-free catalysts for the hydrogenation of carbon dioxide. PMID- 26132912 TI - Low-dose sirolimus controls recurrent iron deficiency in a patient with blue rubber bleb nevus syndrome. PMID- 26132913 TI - Relationship of smartphone use severity with sleep quality, depression, and anxiety in university students. AB - BACKGROUND AND AIMS: The usage of smartphones has increased rapidly in recent years, and this has brought about addiction. The aim of the current study was to investigate the relationship between smartphone use severity and sleep quality, depression, and anxiety in university students. METHODS: In total, 319 university students (203 females and 116 males; mean age = 20.5 +/- 2.45) were included in the study. Participants were divided into the following three groups: a smartphone non-user group (n = 71, 22.3%), a low smartphone use group (n = 121, 37.9%), and a high smartphone use group (n = 127, 39.8%). All participants were evaluated using the Pittsburgh Sleep Quality Index, Beck Depression Inventory, Beck Anxiety Inventory; moreover, participants other than those in the smartphone non-user group were also assessed with the Smartphone Addiction Scale. RESULTS: The findings revealed that the Smartphone Addiction Scale scores of females were significantly higher than those of males. Depression, anxiety, and daytime dysfunction scores were higher in the high smartphone use group than in the low smartphone use group. Positive correlations were found between the Smartphone Addiction Scale scores and depression levels, anxiety levels, and some sleep quality scores. CONCLUSIONS: The results indicate that depression, anxiety, and sleep quality may be associated with smartphone overuse. Such overuse may lead to depression and/or anxiety, which can in turn result in sleep problems. University students with high depression and anxiety scores should be carefully monitored for smartphone addiction. PMID- 26132914 TI - Bipolar spectrum disorders in a clinical sample of patients with Internet addiction: hidden comorbidity or differential diagnosis? AB - BACKGROUND AND AIMS: Behavioral addictions and bipolar disorders have a certain probability of co-occurrence. While the presence of a manic episode has been defined as an exclusion criterion for gambling disorder, no such exclusion has been formulated for Internet addiction. METHODS: A clinical sample of 368 treatment seekers presenting with excessive to addictive Internet use was screened for bipolar spectrum disorders using the Mood Disorder Questionnaire. Psychopathology was assessed by the Symptom Checklist 90R and a clinical interview was administered to screen for comorbid disorders. RESULTS: Comorbid bipolar disorders were more frequent in patients meeting criteria for Internet addiction (30.9%) than among the excessive users (5.6%). This subgroup showed heightened psychopathological symptoms, including substance use disorders, affective disorders and personality disorders. Further differences were found regarding frequency of Internet use regarding social networking sites and online pornography. DISCUSSION: Patients with Internet addiction have a heightened probability for meeting criteria of bipolar disorders. It is not possible to draw conclusions regarding the direction of this association but it is recommended to implement screening for bipolar disorders in patients presenting with Internet addiction. CONCLUSION: Similar to gambling disorder, it might prove necessary to subsume bipolar disorders as an exclusion criterion for the future criteria of Internet addiction. PMID- 26132915 TI - Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy. AB - BACKGROUND: Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. CASE PRESENTATIONS: We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid "bad dreams" remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. RESULTS: The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient's regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. CONCLUSIONS: These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies. PMID- 26132917 TI - Manipulation of Interrenal Cell Function in Developing Zebrafish Using Genetically Targeted Ablation and an Optogenetic Tool. AB - Zebrafish offer an opportunity to study conserved mechanisms underlying the ontogeny and physiology of the hypothalamic-pituitary-adrenal/interrenal axis. As the final effector of the hypothalamic-pituitary-adrenal/interrenal axis, glucocorticoids exert both rapid and long-term regulatory functions. To elucidate their specific effects in zebrafish, transgenic approaches are necessary to complement pharmacological studies. Here, we report a robust approach to specifically manipulate endogenous concentrations of cortisol by targeting heterologous proteins to interrenal cells using a promoter element of the steroidogenic acute regulatory protein. To test this approach, we first used this regulatory region to generate a transgenic line expressing the bacterial nitroreductase protein, which allows conditional targeted ablation of interrenal cells. We demonstrate that this line can be used to specifically ablate interrenal cells, drastically reducing both basal and stress-induced cortisol concentrations. Next, we coupled this regulatory region to an optogenetic actuator, Beggiatoa photoactivated adenylyl cyclase, to increase endogenous cortisol concentrations in a blue light-dependent manner. Thus, our approach allows specific manipulations of steroidogenic interrenal cell activity for studying the effects of both hypo- and hypercortisolemia in zebrafish. PMID- 26132918 TI - Sympathetic Nerve Activity Maintains an Anti-Inflammatory State in Adipose Tissue in Male Mice by Inhibiting TNF-alpha Gene Expression in Macrophages. AB - Adipose tissue macrophages (ATMs) play an important role in the inflammatory response in obese animals. How ATMs are regulated in lean animals has remained elusive, however. We now show that the sympathetic nervous system (SNS) is necessary to maintain the abundance of the mRNA for the proinflammatory cytokine TNF-alpha at a low level in ATMs of lean mice. Intracerebroventricular injection of agouti-related neuropeptide increased the amount of TNF-alpha mRNA in epididymal (epi) white adipose tissue (WAT), but not in interscapular brown adipose tissue (BAT), through inhibition of sympathetic nerve activity in epiWAT. The surgical denervation and beta-adrenergic antagonist propranolol up-regulated TNF-alpha mRNA in both epiWAT and BAT in vivo. Signaling by the beta2-adrenergic receptor (AR) and protein kinase A down-regulated TNF-alpha mRNA in epiWAT explants and suppressed lipopolysaccharide-induced up-regulation of TNF-alpha mRNA in the stromal vascular fraction of this tissue. beta-AR-deficient (beta less) mice manifested an increased plasma TNF-alpha concentration and increased TNF-alpha mRNA abundance in epiWAT and BAT. TNF-alpha mRNA abundance was greater in ATMs (CD11b(+) cells of the stromal vascular fraction) from epiWAT or BAT of wild-type mice than in corresponding CD11b(-) cells, and beta2-AR mRNA abundance was greater in ATMs than in CD11b(-) cells of epiWAT. Our results show that the SNS and beta2-AR-protein kinase A pathway maintain an anti-inflammatory state in ATMs of lean mice in vivo, and that the brain melanocortin pathway plays a role in maintaining this state in WAT of lean mice via the SNS. PMID- 26132919 TI - Glucagon-Like Peptide 2 (GLP-2) Stimulates Postprandial Chylomicron Production and Postabsorptive Release of Intestinal Triglyceride Storage Pools via Induction of Nitric Oxide Signaling in Male Hamsters and Mice. AB - The intestinal overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles is a common feature of diabetic dyslipidemia and contributes to cardiovascular risk in insulin resistant states. We previously reported that glucagon-like peptide-2 (GLP-2) is a key endocrine stimulator of enterocyte fat absorption and chylomicron output in the postprandial state. GLP 2's stimulatory effect on chylomicron production in the postabsorptive state has been confirmed in human studies. The mechanism by which GLP-2 regulates chylomicron production is unclear, because its receptor is not expressed on enterocytes. We provide evidence for a key role of nitric oxide (NO) in mediating the stimulatory effects of GLP-2 during the postprandial and postabsorptive periods. Intestinal chylomicron production was assessed in GLP-2-treated hamsters administered the pan-specific NO synthase (NOS) inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), and in GLP-2-treated endothelial NOS knockout mice. L-NAME blocked GLP-2-stimulated apoB48 secretion and reduced triglycerides (TGs) in the TG-rich lipoprotein (TRL) fraction of the plasma in the postprandial state. Endothelial NOS-deficient mice were resistant to GLP-2 stimulation and secreted fewer large apoB48-particles. When TG storage pools were allowed to accumulate, L NAME mitigated the GLP-2-mediated increase in TRL-TG, suggesting that NO is required for early mobilization and secretion of stored TG and preformed chylomicrons. Importantly, the NO donor S-nitroso-L-glutathione was able to elicit an increase in TRL-TG in vivo and stimulate chylomicron release in vitro in primary enterocytes. We describe a novel role for GLP-2-mediated NO-signaling as a critical regulator of intestinal lipid handling and a potential contributor to postprandial dyslipidemia. PMID- 26132921 TI - Deciphering the Hypoglycemic Glucagon Response: Development of a Graded Hyperinsulinemic Hypoglycemic Clamp Technique in Female Mice. AB - Glucose lowering therapy in type 1 and type 2 diabetes is often associated with hypoglycemic events. To avoid this, glucose lowering therapies need to be developed that support the hypoglycemic defense mechanisms. Such development needs a tool for evaluating counterregulatory mechanisms in vivo. A sustained glucagon release during hypoglycemia is of most importance to hypoglycemic defense mechanisms. We have therefore developed a graded hyperinsulinemic hypoglycemic clamp in mice and used it to evaluate counterregulatory glucagon dynamics. Glucose was clamped at narrow intervals aiming at 2.5, 3.5, 4.5, and 6.0 mmol/L. Glucagon levels were increased during hypoglycemia in a glucose dependent way with a glucagon counterregulatory threshold between 3.5 and 4.0 mmol/L. Modelling the glucose-glucagon relationship using a hyperbolic curve with the equation: plasma glucagon = -4.20 + 90.79/blood glucose showed high correlation. When comparing this method to the insulin tolerance test as an approach to study glucagon dynamics in vivo, we found that the graded clamp more efficiently evoked a robust, predictable, glucagon response with considerably less variation in blood glucose. In conclusion, we have developed a tool for the study of in vivo glucagon dynamics during hypoglycemia in mice and demonstrated a hyperbolic glucose-counterregulatory glucagon relationship. PMID- 26132920 TI - The Effects of a Single Developmentally Entrained Pulse of Testosterone in Female Neonatal Mice on Reproductive and Metabolic Functions in Adult Life. AB - Early postnatal exposures to sex steroids have been well recognized to modulate predisposition to diseases of adulthood. There is a complex interplay between timing, duration and dose of endocrine exposures through environmental or dietary sources that may alter the sensitivity of target tissues to the exogenous stimuli. In this study, we determined the metabolic and reproductive programming effects of a single developmentally entrained pulse of testosterone (T) given to female mice in early postnatal period. CD-1 female mice pups were injected with either 5 MUg of T enanthate (TE) or vehicle (control [CON] group) within 24 hours after birth and followed to adult age. A total of 66% of T-treated mice exhibited irregular cycling, anovulatory phenotype, and significantly higher ovarian weights than vehicle-treated mice. Longitudinal nuclear magnetic resonance measurements revealed that TE group had greater body weight, whole-body lean, and fat mass than the CON group. Adipose tissue cellularity analysis in TE group revealed a trend toward higher size and number than their littermate CONs. The brown adipose tissue of TE mice exhibited white fat infiltration with down regulation of several markers, including uncoupling protein 1 (UCP-1), cell death inducing DNA fragmentation factor, alpha-subunit-like effector A, bone morphogenetic protein 7 as well as brown adipose tissue differentiation-related transcription regulators. T-injected mice were also more insulin resistant than CON mice. These reproductive and metabolic reprogramming effects were not observed in animals exposed to TE at 3 and 6 weeks of age. Collectively, these data suggest that sustained reproductive and metabolic alterations may result in female mice from a transient exposure to T during a narrow postnatal developmental window. PMID- 26132922 TI - Simultaneous Nanoscale Surface Charge and Topographical Mapping. AB - Nanopipettes are playing an increasingly prominent role in nanoscience, for sizing, sequencing, delivery, detection, and mapping interfacial properties. Herein, the question of how to best resolve topography and surface charge effects when using a nanopipette as a probe for mapping in scanning ion conductance microscopy (SICM) is addressed. It is shown that, when a bias modulated (BM) SICM scheme is used, it is possible to map the topography faithfully, while also allowing surface charge to be estimated. This is achieved by applying zero net bias between the electrode in the SICM tip and the one in bulk solution for topographical mapping, with just a small harmonic perturbation of the potential to create an AC current for tip positioning. Then, a net bias is applied, whereupon the ion conductance current becomes sensitive to surface charge. Practically this is optimally implemented in a hopping-cyclic voltammetry mode where the probe is approached at zero net bias at a series of pixels across the surface to reach a defined separation, and then a triangular potential waveform is applied and the current response is recorded. Underpinned with theoretical analysis, including finite element modeling of the DC and AC components of the ionic current flowing through the nanopipette tip, the powerful capabilities of this approach are demonstrated with the probing of interfacial acid-base equilibria and high resolution imaging of surface charge heterogeneities, simultaneously with topography, on modified substrates. PMID- 26132923 TI - The Cell Cycle Timing of Human Papillomavirus DNA Replication. AB - Viruses manipulate the cell cycle of the host cell to optimize conditions for more efficient viral genome replication. One strategy utilized by DNA viruses is to replicate their genomes non-concurrently with the host genome; in this case, the viral genome is amplified outside S phase. This phenomenon has also been described for human papillomavirus (HPV) vegetative genome replication, which occurs in G2-arrested cells; however, the precise timing of viral DNA replication during initial and stable replication phases has not been studied. We developed a new method to quantitate newly synthesized DNA levels and used this method in combination with cell cycle synchronization to show that viral DNA replication is initiated during S phase and is extended to G2 during initial amplification but follows the replication pattern of cellular DNA during S phase in the stable maintenance phase. E1 and E2 protein overexpression changes the replication time from S only to both the S and G2 phases in cells that stably maintain viral episomes. These data demonstrate that the active synthesis and replication of the HPV genome are extended into the G2 phase to amplify its copy number and the duration of HPV genome replication is controlled by the level of the viral replication proteins E1 and E2. Using the G2 phase for genome amplification may be an important adaptation that allows exploitation of changing cellular conditions during cell cycle progression. We also describe a new method to quantify newly synthesized viral DNA levels and discuss its benefits for HPV research. PMID- 26132924 TI - Data Mining Approaches for Genomic Biomarker Development: Applications Using Drug Screening Data from the Cancer Genome Project and the Cancer Cell Line Encyclopedia. AB - Developing reliable biomarkers of tumor cell drug sensitivity and resistance can guide hypothesis-driven basic science research and influence pre-therapy clinical decisions. A popular strategy for developing biomarkers uses characterizations of human tumor samples against a range of cancer drug responses that correlate with genomic change; developed largely from the efforts of the Cancer Cell Line Encyclopedia (CCLE) and Sanger Cancer Genome Project (CGP). The purpose of this study is to provide an independent analysis of this data that aims to vet existing and add novel perspectives to biomarker discoveries and applications. Existing and alternative data mining and statistical methods will be used to a) evaluate drug responses of compounds with similar mechanism of action (MOA), b) examine measures of gene expression (GE), copy number (CN) and mutation status (MUT) biomarkers, combined with gene set enrichment analysis (GSEA), for hypothesizing biological processes important for drug response, c) conduct global comparisons of GE, CN and MUT as biomarkers across all drugs screened in the CGP dataset, and d) assess the positive predictive power of CGP-derived GE biomarkers as predictors of drug response in CCLE tumor cells. The perspectives derived from individual and global examinations of GEs, MUTs and CNs confirm existing and reveal unique and shared roles for these biomarkers in tumor cell drug sensitivity and resistance. Applications of CGP-derived genomic biomarkers to predict the drug response of CCLE tumor cells finds a highly significant ROC, with a positive predictive power of 0.78. The results of this study expand the available data mining and analysis methods for genomic biomarker development and provide additional support for using biomarkers to guide hypothesis-driven basic science research and pre-therapy clinical decisions. PMID- 26132925 TI - Hg Stable Isotope Time Trend in Ringed Seals Registers Decreasing Sea Ice Cover in the Alaskan Arctic. AB - Decadal time trends of mercury (Hg) concentrations in Arctic biota suggest that anthropogenic Hg is not the single dominant factor modulating Hg exposure to Arctic wildlife. Here, we present Hg speciation (monomethyl-Hg) and stable isotopic composition (C, N, Hg) of 53 Alaskan ringed seal liver samples covering a period of 14 years (1988-2002). In vivo metabolic effects and foraging ecology explain most of the observed 1.6 0/00 variation in liver delta(202)Hg, but not Delta(199)Hg. Ringed seal habitat use and migration were the most likely factors explaining Delta(199)Hg variations. Average Delta(199)Hg in ringed seal liver samples from Barrow increased significantly from +0.38 +/- 0.080/00 (+/-SE, n = 5) in 1988 to +0.59 +/- 0.070/00 (+/-SE, n = 7) in 2002 (4.1 +/- 1.2% per year, p < 0.001). Delta(199)Hg in marine biological tissues is thought to reflect marine Hg photochemistry before biouptake and bioaccumulation. A spatiotemporal analysis of sea ice cover that accounts for the habitat of ringed seals suggests that the observed increase in Delta(199)Hg may have been caused by the progressive summer sea ice disappearance between 1988 and 2002. While changes in seal liver Delta(199)Hg values suggests a mild sea ice control on marine MMHg breakdown, the effect is not large enough to induce measurable HgT changes in biota. This suggests that Hg trends in biota in the context of a warming Arctic are likely controlled by other processes. PMID- 26132926 TI - Inflammatory Factors in Reproductive Medicine. PMID- 26132927 TI - Inflammatory Factors in Reproductive Medicine. PMID- 26132928 TI - Vulvodynia: The Role of Inflammation in the Etiology of Localized Provoked Pain of the Vulvar Vestibule (Vestibulodynia). AB - Vulvar pain affecting the vestibule (vestibulodynia) is an enigmatic pain disorder that greatly affects quality of life and sexual functioning. The most common form of the disorder (localized provoked vulvodynia) is initiated by genital contact but is otherwise asymptomatic. Findings on examination are limited to excessive tenderness of the vestibule with light touch with cotton swab but may also include localized erythema and pelvic floor muscle tightness and tenderness. This review will summarize the literature regarding the role of inflammation in the genesis of the disorder. Some evidence exists for altered histology consisting of increased numbers of mast cells and nerve endings. Immunological abnormalities that have been reported include altered cytokines and neurokines. Abnormal inflammatory response and heightened sensitivity of the vaginal opening has been documented in a murine model of vaginal infection with Candida albicans. In vitro studies of fibroblasts from the vestibule of affected women with vestibulodynia demonstrate a proinflammatory response to C albicans that may be important in the initiation of pain. However, thus far none of the findings have led to adequate treatments. PMID- 26132930 TI - The Emerging Role of Chronic Low-Grade Inflammation in the Pathophysiology of Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) has become increasingly common over recent years and is associated with reproductive features as well as cardiometabolic risk factors, including visceral obesity, dyslipidemia and impaired glucose homeostasis, and potentially cardiovascular disease. Emerging evidence suggests that these long-term metabolic effects are linked to a low-grade chronic inflammatory state with the triad of hyperinsulinemia, hyperandrogenism, and low grade inflammation acting together in a vicious cycle in the pathophysiology of PCOS. Dysregulation of the sympathetic nervous system may also act as an important component, potentially creating a tetrad in the pathophysiology of PCOS. The aim of this review is to examine the role of chronic inflammation and the sympathetic nervous system in the development of obesity and PCOS and review potential therapeutic options to alleviate low-grade inflammation in this setting. PMID- 26132932 TI - Nutrient-Induced Inflammation in Polycystic Ovary Syndrome: Role in the Development of Metabolic Aberration and Ovarian Dysfunction. AB - A pathophysiology paradigm shift has emerged with the discovery that polycystic ovary syndrome (PCOS) is a proinflammatory state. Despite the dogma that the compensatory hyperinsulinemia of insulin resistance is the promoter of hyperandrogenism, physiological insulin infusion has no effect on androgen levels in PCOS. The dogma also does not explain the cause of hyperandrogenism and ovarian dysfunction in the 30 to 50% of women with PCOS who are of normal weight and lack insulin resistance. Inflammation is the underpinning of insulin resistance in obesity and type 2 diabetes, and may also be the cause of insulin resistance when present in PCOS. The origin of inflammation in PCOS has been ascribed to excess abdominal adiposity or frank obesity. However, nutrients such as glucose and saturated fat can incite inflammation from circulating mononuclear cells (MNC) of women with PCOS independent of excess adiposity and insulin resistance, and can also promote atherogenesis. Hyperandrogenism activates MNC in the fasting state to increase MNC sensitivity to nutrients, and is a potential mechanism for initiating inflammation in PCOS. However, chronic ovarian androgen suppression does not reduce inflammation in normal-weight women with PCOS. Direct exposure of ovarian theca cells to proinflammatory stimuli in vitro increases androgen production. These findings may be corroborated in vivo with anti inflammatory therapy to normal-weight insulin-sensitive women with PCOS without abdominal adiposity to observe for amelioration of ovarian dysfunction. PMID- 26132929 TI - Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways. AB - Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease. PMID- 26132931 TI - Inflammation and Human Ovarian Follicular Dynamics. AB - Inflammation is a biologic process that mediates tissue effects including vasodilation, hyperemia, edema, collagenolysis, and cell proliferation through complex immunologic pathways. In regard to the ovary, inflammation has key physiologic roles in ovarian folliculogenesis and ovulation. On the other hand, inflammatory processes are subject to underlying pathology and, if pushed, proinflammatory conditions may have a negative impact on ovarian follicular dynamics. Obesity and polycystic ovary syndrome (PCOS) serve as examples of conditions associated with chronic endogenous production of low-grade proinflammatory cytokines. Both conditions negatively impact ovarian folliculogenesis and ovulation. The pages that follow summarize the role of inflammation in normal ovarian follicular dynamics and evidence for its role in mediating the negative effects of obesity and PCOS on ovarian follicular dynamics. The review concludes with a summary supporting a role for lifestyle factors that favorably impact inflammatory process involved in obesity and PCOS to improve ovarian function. PMID- 26132933 TI - Gap Junctions in Leiomyomas and the Human Female Reproductive Tract. AB - The aim of the study was to critically examine existing data on the contribution of gap junctions to the function of the female reproductive tract and their role in cancer and benign gynecologic disease such as uterine leiomyomas and to evaluate the potential for clinical applications of gap junction intercellular communication (GJIC) in the treatment of diseases of the female reproductive tract. Gap junction proteins are present in all organs of the female reproductive tract. GJIC is vital to folliculogenesis, embryo implantation, and vascular changes associated with pregnancy and synchronization of uterine contractions of parturition. Loss of GJIC is associated with malignancy, and therapeutic restoration of GJIC reduces tumor growth and reverses chemotherapy resistance. GJIC is critical for various cell and tissue functions including the function of the female reproductive tract. Exploitation of the properties of GJIC may lead to novel treatments for both benign and malignant gynecologic diseases. GJIC is critical for various cell and tissue functions including specialized functions of the female reproductive tract and potential maintenance of the benign behavior of uterine leiomyomas. PMID- 26132934 TI - The Role of Inflammatory Pathways in Implantation Failure: Chronic Endometritis and Hydrosalpinges. AB - The process of implantation is highly complex and involves a delicate interplay between the embryo and the appropriate maternal environment. The failure to implant is thought to be due to maternal factors or embryonic factors. Inflammation can be a part of the normal physiologic process during implantation; however, there are also pathologic entities that adversely affect uterine receptivity. This review will focus on chronic endometritis and hydrosalpinges as two specific inflammatory processes that contribute to implantation failure. For both chronic endometritis and hydrosalpinges, we will review the diagnosis, pathophysiology, and effect on implantation following treatment. The existing literature conclusively demonstrates that hydrosalpinges should be addressed by either laparoscopic salpingectomy or proximal tubal occlusion prior to in vitro fertilization. The picture for chronic endometritis is less clear since the diagnosis and treatment of chronic endometritis are not standardized, and there are no available randomized controlled trials on this topic. Future studies may target gene expression arrays as a method for further elucidating the role of inflammatory markers in normal and abnormal implantation processes. PMID- 26132935 TI - Immune Function and Recurrent Pregnancy Loss. AB - Recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages, is attributable to multiple causes. However, in 50% of cases no known cause is found. Although endometritis is a known cause of miscarriage, other inflammatory processes may play a role in idiopathic, recurrent loss. The fetoplacental unit evades rejection by the maternal immune system by poorly understood mechanisms. Despite this seemingly immune-privileged state for the fetus, human implantation requires inflammatory mediators for attachment and implantation. This review describes how the immune system must simultaneously permit and restrict trophoblastic invasion for healthy implantation and maintenance of pregnancy. Included in this review is a detailed description of the immune milieu in the decidua and abnormalities that are associated with RPL. Finally, autoimmune states associated with RPL and their treatment in an obstetrical setting are reviewed. PMID- 26132936 TI - Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors. AB - BACKGROUND: A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. METHODS: Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores <= -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry. RESULTS: The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion. CONCLUSIONS: A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer driver gene. PMID- 26132937 TI - India's Aspirations for Universal Health Coverage. PMID- 26132938 TI - Placebo Effects in Medicine. PMID- 26132940 TI - Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia. AB - BACKGROUND: In patients with acquired aplastic anemia, destruction of hematopoietic cells by the immune system leads to pancytopenia. Patients have a response to immunosuppressive therapy, but myelodysplastic syndromes and acute myeloid leukemia develop in about 15% of the patients, usually many months to years after the diagnosis of aplastic anemia. METHODS: We performed next generation sequencing and array-based karyotyping using 668 blood samples obtained from 439 patients with aplastic anemia. We analyzed serial samples obtained from 82 patients. RESULTS: Somatic mutations in myeloid cancer candidate genes were present in one third of the patients, in a limited number of genes and at low initial variant allele frequency. Clonal hematopoiesis was detected in 47% of the patients, most frequently as acquired mutations. The prevalence of the mutations increased with age, and mutations had an age-related signature. DNMT3A mutated and ASXL1-mutated clones tended to increase in size over time; the size of BCOR- and BCORL1-mutated and PIGA-mutated clones decreased or remained stable. Mutations in PIGA and BCOR and BCORL1 correlated with a better response to immunosuppressive therapy and longer and a higher rate of overall and progression free survival; mutations in a subgroup of genes that included DNMT3A and ASXL1 were associated with worse outcomes. However, clonal dynamics were highly variable and might not necessarily have predicted the response to therapy and long-term survival among individual patients. CONCLUSIONS: Clonal hematopoiesis was prevalent in aplastic anemia. Some mutations were related to clinical outcomes. A highly biased set of mutations is evidence of Darwinian selection in the failed bone marrow environment. The pattern of somatic clones in individual patients over time was variable and frequently unpredictable. (Funded by Grant-in Aid for Scientific Research and others.). PMID- 26132943 TI - IMAGES IN CLINICAL MEDICINE. Subglottic Stenosis. PMID- 26132939 TI - A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. AB - BACKGROUND: Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS: We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS: At baseline, the mean (+/-SD) age of the patients was 45.1+/-12.0 years, the mean weight was 106.2+/-21.4 kg, and the mean BMI was 38.3+/-6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4+/-7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8+/-6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS: In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.). PMID- 26132941 TI - Afamelanotide for Erythropoietic Protoporphyria. AB - BACKGROUND: Erythropoietic protoporphyria is a severe photodermatosis that is associated with acute phototoxicity. Patients with this condition have excruciating pain and a markedly reduced quality of life. We evaluated the safety and efficacy of an alpha-melanocyte-stimulating hormone analogue, afamelanotide, to decrease pain and improve quality of life. METHODS: We conducted two multicenter, randomized, double-blind, placebo-controlled trials of subcutaneous implants containing 16 mg of afamelanotide. Patients in the European Union (74 patients) and the United States (94 patients) were randomly assigned, in a 1:1 ratio, to receive a subcutaneous implant containing either afamelanotide or placebo every 60 days (a total of five implants in the European Union study and three in the U.S study). The type and duration of sun exposure, number and severity of phototoxic reactions, and adverse events were recorded over the respective 180-day and 270-day study periods. Quality of life was assessed with the use of validated questionnaires. A subgroup of U.S. patients underwent photoprovocation testing. The primary efficacy end point was the number of hours of direct exposure to sunlight without pain. RESULTS: In the U.S. study, the duration of pain-free time after 6 months was longer in the afamelanotide group (median, 69.4 hours, vs. 40.8 hours in the placebo group; P=0.04). In the European Union study, the duration of pain-free time after 9 months was also longer in the afamelanotide group than in the placebo group (median, 6.0 hours vs. 0.8 hours; P=0.005), and the number of phototoxic reactions was lower in the the afamelanotide group (77 vs. 146, P=0.04). In both trials, quality of life improved with afamelanotide therapy. Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug. CONCLUSIONS: Afamelanotide had an acceptable side-effect and adverse-event profile and was associated with an increased duration of sun exposure without pain and improved quality of life in patients with erythropoietic protoporphyria. (Funded by Clinuvel Pharmaceuticals and others; ClinicalTrials.gov numbers, NCT01605136 and NCT00979745.). PMID- 26132942 TI - An Integrated View of Potassium Homeostasis. PMID- 26132944 TI - CLINICAL PROBLEM-SOLVING. A Man with Fever, Cough, and Rash. PMID- 26132945 TI - Another Agent for Obesity--Will This Time Be Different? PMID- 26132946 TI - Causality and Chance in the Development of Cancer. PMID- 26132947 TI - Anatomical versus Functional Testing for Coronary Artery Disease. PMID- 26132948 TI - Anatomical versus Functional Testing for Coronary Artery Disease. PMID- 26132949 TI - Anatomical versus Functional Testing for Coronary Artery Disease. PMID- 26132950 TI - Anatomical versus Functional Testing for Coronary Artery Disease. PMID- 26132951 TI - Anatomical versus Functional Testing for Coronary Artery Disease. PMID- 26132952 TI - Vaccine against Pneumococcal Pneumonia in Adults. PMID- 26132953 TI - Vaccine against Pneumococcal Pneumonia in Adults. PMID- 26132954 TI - Vaccine against Pneumococcal Pneumonia in Adults. PMID- 26132955 TI - Vaccine against Pneumococcal Pneumonia in Adults. PMID- 26132957 TI - Chikungunya Virus Infections. PMID- 26132956 TI - Chikungunya Virus Infections. PMID- 26132958 TI - Chikungunya Virus Infections. PMID- 26132959 TI - Fibrosis--A Common Pathway to Organ Injury and Failure. PMID- 26132961 TI - Fibrosis--A Common Pathway to Organ Injury and Failure. PMID- 26132960 TI - Fibrosis--A Common Pathway to Organ Injury and Failure. PMID- 26132962 TI - Real-Time Localization of Parathyroid Adenoma during Parathyroidectomy. PMID- 26132963 TI - IMAGES IN CLINICAL MEDICINE. Jaccoud's Arthropathy. PMID- 26132964 TI - Neuro-Ophthalmic Syndromes and Processing Speed in Multiple Sclerosis. AB - The impact of prior neuro-ophthalmic syndromes on the performance on vision-based neuropsychological tasks in patients with multiple sclerosis (MS) is unknown. Two groups of MS participants, one with (Msos+) and the other without (Msos-), a history of neuro-ophthalmic syndromes, underwent neuropsychological assessment and were compared with healthy age- and education-matched controls (HC). Participants with Msos+ performed significantly worse on the symbol digit modalities test than the Msos- (P < 0.03) and the HC groups (P < 0.01) and coding (P < 0.01). A clinical history of neuro-ophthalmic syndromes is associated with reduced performance on visual processing speed tasks. PMID- 26132965 TI - Hemorrhage Within the Optic Nerve From a Cavernous Hemangioma of the Optic Disc. AB - A 49-year-old woman with a known right optic disc cavernous hemangioma experienced pain with eye movements and worsening of a superior visual field defect. While she retained 20/20 visual acuity in each eye, findings on magnetic resonance imaging were consistent with a hemorrhage in the anterior portion of the right intraorbital optic nerve. Her visual function stabilized spontaneously. We are unaware of previous reports of hemorrhage into the optic nerve from a cavernous hemangioma of the optic disc. PMID- 26132966 TI - Progressive Multifocal Leukoencephalopathy: Recent Advances and a Neuro Ophthalmological Review. AB - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe often fatal opportunistic infection of the central nervous system caused by reactivation of a ubiquitous polyoma virus, JC virus. Although typically characterized by multifocal asymmetric subcortical white matter lesions, it may be monofocal and affect the cortical gray matter. Among the broad spectrum of clinical manifestations that occurs with PML, visual complaints are common. EVIDENCE ACQUISITION: Combination of representative personally observed cases of PML and comprehensive review of case series of PML from 1958 through 2014. RESULTS: Neuro-ophthalmic signs and symptoms were reported in approximately 20% 50% of patients with PML and can be the presenting manifestation in half of these. A majority of these presentations occur from damage to cerebral visual pathways resulting in visual field defects, cortical blindness, and other disorders of visual association. Given the decreased frequency of infratentorial and cerebellar involvement, ocular motility disorders are less common. CONCLUSIONS: Visual complaints occur in patients with PML and are often the presenting sign. Awareness of this condition is helpful in avoiding unnecessary delays in the diagnosis of PML and management of the underlying condition. Recent guidelines have established criteria for diagnosis of PML in the high-risk patient population and strategies to mitigate the risk in these populations. PMID- 26132967 TI - Refractory knee giant cell tumor of the synovial membrane treated with intra articular injection of Infliximab: a case series and review of the literature. AB - Giant cell tumor (GCT) of the synovial membrane, also known as pigmented villonodular synovitis, causes a progressive, relapsing and destructive arthropathy affecting one or more synovial joints. Systemic therapy can be combined to intra-articular treatments, including surgical synoviectomy, especially when monoarticular. Despite that, the synovial membrane commonly grows again with clinical relapse. Here, we report three case of patients diagnosed with GCT of the knee who had an early relapse of the disease even after surgical synoviectomy. All of them underwent intra-articular therapy with infliximab and subsequent synoviectomy to eradicate residual tissue. A complete remission of CGT was achieved without relapse occurring during the follow-up. These preliminary data need to be confirmed by further clinical trials; however, intra-articular therapy with infliximab might be deemed a potential option to treat CGT of a single joint. PMID- 26132974 TI - An Efficient Method for Identifying Gene Fusions by Targeted RNA Sequencing from Fresh Frozen and FFPE Samples. AB - Fusion genes are known to be key drivers of tumor growth in several types of cancer. Traditionally, detecting fusion genes has been a difficult task based on fluorescent in situ hybridization to detect chromosomal abnormalities. More recently, RNA sequencing has enabled an increased pace of fusion gene identification. However, RNA-Seq is inefficient for the identification of fusion genes due to the high number of sequencing reads needed to detect the small number of fusion transcripts present in cells of interest. Here we describe a method, Single Primer Enrichment Technology (SPET), for targeted RNA sequencing that is customizable to any target genes, is simple to use, and efficiently detects gene fusions. Using SPET to target 5701 exons of 401 known cancer fusion genes for sequencing, we were able to identify known and previously unreported gene fusions from both fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissue RNA in both normal tissue and cancer cells. PMID- 26132976 TI - A novel approach for the synthesis of ultrathin silica-coated iron oxide nanocubes decorated with silver nanodots (Fe3O4/SiO2/Ag) and their superior catalytic reduction of 4-nitroaniline. AB - A novel sonochemical approach was developed for the synthesis of different core/shell structures of Fe3O4/SiO2/Ag nanocubes and SiO2/Ag nanospheres. The total reaction time of the three sonochemical steps for the synthesis of Fe3O4/SiO2/Ag nanocubes is shorter than that of the previously reported methods. A proposed reaction mechanism for the sonochemical functionalization of the silica and the silver on the surface of magnetic nanocubes was discussed in detail. Transmission electron microscopy revealed that the surface of Fe3O4/SiO2 nanocubes was decorated with small Ag nanoparticles of approximately 10-20 nm in size, and the energy dispersive spectroscopy mapping analysis confirmed the morphology of the structure. Additionally, X-ray diffraction data were used to confirm the formation of both phases of a cubic inverse spinel structure for Fe3O4 and bcc structures for Ag in the core/shell structure of the Fe3O4/SiO2/Ag nanocubes. The as-synthesized Fe3O4/SiO2/Ag nanocubes showed a high efficiency in the catalytic reduction reaction of 4-nitroaniline to 4-phenylenediamine and a better performance than both Ag and SiO2/Ag nanoparticles. The grafted silver catalyst was recycled and reused at least fifteen times without a significant loss of catalytic efficiency. PMID- 26132975 TI - DNA Polyplexes as Combinatory Drug Carriers of Doxorubicin and Cisplatin: An in Vitro Study. AB - Double helix nucleic acids were used as a combination drug carrier for doxorubicin (DOX), which physically intercalates with DNA double helices, and cisplatin (CDDP), which binds to DNA without an alkylation reaction. DNA interacting with DOX, CDDP, or both was complexed with positively charged, endosomolytic polymers. Compared with the free drug, the polyplexes (100-170 nm in size) delivered more drug into the cytosol and the nucleus and demonstrated similar or superior (up to a 7-fold increase) in vitro cell-killing activity. Additionally, the gene expression activities of most of the chemical drug-loaded plasmid DNA (pDNA) polyplexes were not impaired by the physical interactions between the nucleic acid and DOX/CDDP. When a model reporter pDNA (luciferase) was employed, it expressed luciferase protein at 0.7- to 1.4-fold the amount expressed by the polyplex with no bound drugs (a control), which indicated the fast translocation of the intercalated or bound drugs from the "carrier DNA" to the "nuclear DNA" of target cells. The proposed concept may offer the possibility of versatile combination therapies of genetic materials and small molecule drugs that bind to nucleic acids to treat various diseases. PMID- 26132977 TI - Industry Funded Continuing Medical Education: The Potential for Bias. PMID- 26132978 TI - Withdrawing or Withholding Life-Sustaining Therapy. PMID- 26132980 TI - FLAMSA reduced-intensity conditioning is equally effective in AML patients with primary induction failure as well as in first or second complete remission. AB - Reduced-intensity conditioning regimens have demonstrated lower toxicity but increased relapse rates in the context of allogeneic hematopoietic stem cell transplantation (aSCT) for patients with acute myelogenous leukemia (AML). The FLAMSA- reduced-intensity conditioning (RIC) regimen, combining a cytoreductive and a transplant-conditioning part, has been described to be efficacious in patients with refractory disease. We retrospectively analyzed clinical data of 130 patients with AML after aSCT following FLAMSA RIC at our center. The median follow-up was 37 (10-125) months. The 4-yr overall and disease-free survival rates of the whole cohort were 45% and 40%. Cumulative incidence of relapse was 29%, 35%, and 40% at 1, 2, and 4 yr. There were no significant differences regarding overall and disease-free survival for patients transplanted in CR1, CR2, or primary induction failure (PIF). Patients with refractory disease after salvage therapy had significantly lower disease-free and overall survival (OS). Disease-free and OS rates were also significantly decreased in patients with 10% or more BLASTS at transplant. non-relapse mortality was 15%, 19%, and 20% at 1, 2, and 4 yr and similar in all cohorts. These data underscore the potency of the FLAMSA RIC regimen for patients with AML especially with PIF. The decision for re induction therapy prior to aSCT in relapsed patients has to be weighed against the potential toxicity of this approach and might be influenced by the amount of leukemic BLASTS present. Only randomised trials will answer this important question. PMID- 26132979 TI - Systems Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting. AB - In a recent National Research Council document, new strategies for risk assessment were described to enable more accurate and quicker assessments. This report suggested that evaluating individual responses through increased use of bio-monitoring could improve dose-response estimations. Identification of specific biomarkers may be useful for diagnostics or risk prediction as they have the potential to improve exposure assessments. This paper discusses systems biology, biomarkers of effect, and computational toxicology approaches and their relevance to the occupational exposure limit setting process. The systems biology approach evaluates the integration of biological processes and how disruption of these processes by chemicals or other hazards affects disease outcomes. This type of approach could provide information used in delineating the mode of action of the response or toxicity, and may be useful to define the low adverse and no adverse effect levels. Biomarkers of effect are changes measured in biological systems and are considered to be preclinical in nature. Advances in computational methods and experimental -omics methods that allow the simultaneous measurement of families of macromolecules such as DNA, RNA, and proteins in a single analysis have made these systems approaches feasible for broad application. The utility of the information for risk assessments from -omics approaches has shown promise and can provide information on mode of action and dose-response relationships. As these techniques evolve, estimation of internal dose and response biomarkers will be a critical test of these new technologies for application in risk assessment strategies. While proof of concept studies have been conducted that provide evidence of their value, challenges with standardization and harmonization still need to be overcome before these methods are used routinely. PMID- 26132981 TI - Cyclodextrin-Based Solid-Gas Clathrates. AB - "Cyclodextrin-gas" clathrates were obtained by crystallization from water solution of alpha-, beta-, and gamma-cyclodextrins (CDs) under pressure of the gas to be entrapped into the CD molecules. When the pressure is released, these clathrates are stable at ambient conditions and dissociate at elevated temperature, which makes them interesting for various applications as foam boosters in food and other industries. It was found that under these conditions alpha-CD forms clathrates with all of the gases used in this study (N2, N2O, CO2, Ar), whereas beta- and gamma-CDs can form clathrates only with N2. The concentration of the cyclodextrin and the temperature and pressure of the gas were varied for achieving higher clathrate yield and larger amount of embedded gas. Highest values of about 2 wt % were found for alpha-CD-N2O, as it releases in the temperature range of 40-60 degrees C. PMID- 26132982 TI - Structural Ensemble of CD4 Cytoplasmic Tail (402-419) Reveals a Nearly Flat Free Energy Landscape with Local alpha-Helical Order in Aqueous Solution. AB - The human cluster determinant 4 (CD4), expressed primarily on the surface of T helper cells, serves as a coreceptor in T-cell receptor recognition of MHC II antigen complexes. Besides its cellular functions, CD4 serves as a primary receptor of human immunodeficiency virus (HIV) type 1. The cytoplasmic tail of CD4 (residues 402-419) is known to be involved in direct interaction with the HIV 1 proteins Vpu and Nef. These two viral accessory proteins (Vpu and Nef) downregulate CD4 in HIV-1 infected cells by multiple strategies and make the body susceptible to all forms of infections. In this work, we carried out extensive replica exchange molecular dynamics simulations in explicit water with three popular protein force fields Amber ff99SB, Amber ff99SB*-ILDN, and CHARMM36 to characterize the equilibrium conformational ensemble of CD4-tail (402-419) and further validated the simulated ensembles with known NMR data. We found that ff99SB*-ILDN gives a better description of the structural ensemble of this peptide compared with ff99SB and CHARMM36. The peptide adopts multiple distinct conformations with varying degree of residual secondary structures. In particular, we observed 28, 7, and 5% average alpha-helical, beta-strand, and 3(10)-helix content, respectively, for ff99SB*-ILDN. The peptide chain shows the tendency of helix formation in a cooperative manner, seeding at residues 407-410, and subsequently extending toward both ends of the chain. Furthermore, we constructed Markov state model (MSM) from large-scale molecular dynamics simulations to study the dynamics of transitions between different metastable states explored by this peptide. The mean first passage times computed from MSM indicate rapid interconversion of these states, and the time scales of transitions range from several nanoseconds to hundreds of microseconds. Our results show good agreement with experimental data and could help to understand the key molecular mechanisms of T-cell activation and HIV-mediated receptor interference. PMID- 26132983 TI - Implementing the Modified 2009 American Thyroid Association Risk Stratification System in Thyroid Cancer Patients with Low and Intermediate Risk of Recurrence. AB - OBJECTIVE: The primary purpose of this study was to validate the proposed modified 2009 American Thyroid Association Risk Stratification System (M-2009 RSS) in patients with thyroid cancer and to compare the findings with those of the 2009 ATA Risk of Recurrence (2009 ATA-RR) and the Ongoing Risk of recurrence system. The secondary purpose was to assess which risk stratification system had the best predictive value to foresee the probability of structural incomplete response or the no evidence of disease (NED) status at the end of follow-up. SUBJECTS AND METHODS: This retrospective review included 149 patients with differentiated thyroid cancer who had low and intermediate 2009 ATA-RR and were treated at a single experienced center and followed-up for a median of 6 years (range 3-12 years). Each patient was risk stratified using both the 2009 ATA-RR and the M-2009-RSS. The primary endpoints were 1) the best response to initial therapy defined as either excellent response, biochemical or structural incomplete response, or indeterminate response; 2) clinical status at final follow-up defined as either NED, biochemical incomplete response, structural incomplete response, indeterminate response, or recurrence (biochemical or structural disease identified after a period of NED), and 3) ongoing RR defined as low or high risk according several outcomes after initial treatment. RESULTS: Mean age of included patients was 45.3+/-13 years. Both the ATA 2009-RR and the M 2009-RSS provided clinically meaningful graded estimates with regard to the status of NED at the end of follow-up in low-risk patients (84% for 2009 ATA-RR and 74% for M-2009-RSS) or the likelihood of having persistent structural disease (0% for 2009 ATA RR and 3.6% for the M-2009-RSS). When patients were classified as low risk, the positive predictive value (PPV) and negative predictive value (NPV) to predict structural disease was 0% and 88.7% for the 2009 ATA-RR, 3.6% and 86.5% for the M-2009-RSS, and 1.6% and 68.2% for the ongoing RR (p=0.022 and 0.055 of chi-square test for PPV and NPV, respectively). CONCLUSIONS: Despite expanding the definition of low risk to include small-volume lymph node metastases, minor extrathyroidal extension, and minimally invasive follicular thyroid cancer, the M-2009-RSS predicts clinical outcomes (structural incomplete response and NED at the end of follow-up) that are very similar to the previously validated 2009 ATA RR classification system. PMID- 26132984 TI - A microporous lanthanum metal-organic framework as a bi-functional chemosensor for the detection of picric acid and Fe(3+) ions. AB - A microporous lanthanum metal-organic framework [La(TPT)(DMSO)2].H2O (La-MOF ()), has been synthesized using a rigid unsymmetrical tricarboxylate ligand of p terphenyl-3,4'',5-tricarboxylic acid (H3TPT). The structure of is constructed by bi-nuclear lanthanum clusters and fully deprotonated TPT(3-) ligands, which can be simplified into a 3,6-connected flu-3,6-C2/c topology with a point symbol of (4(4).6)2(4.6(2).8(7).10(2)). The pi-electron rich ligand H3TPT enables to have blue luminescence when excited at 342 nm at ambient temperature. Meanwhile, exhibits the selective detection of picric acid (PA) and Fe(3+) ions in ethanol solution over other nitroaromatic compounds and metal ions. The high quenching efficiency and selectivity of makes it a potential bi-functional chemosensor for both PA and Fe(3+) ions. PMID- 26132985 TI - Failure of sugammadex to reverse rocuronium-induced neuromuscular blockade: Simply an outlier or are we missing something? PMID- 26132986 TI - Towards plant protein refinery: Review on protein extraction using alkali and potential enzymatic assistance. AB - The globally increasing protein demands require additional resources to those currently available. Furthermore, the optimal usage of protein fractions from both traditional and new protein resources, such as algae and leaves, is essential. Here, we present an overview on alkaline plant protein extraction including the potentials of enzyme addition in the form of proteases and/or carbohydrolases. Strategic biomass selection, combined with the appropriate process conditions can increase protein yields after extraction. Enzyme addition, especially of proteases, can be useful when alkaline protein extraction yields are low. These additions can also be used to enable processing at a pH closer to 7 to avoid the otherwise severe conditions that denature proteins. Finally, a protein biorefinery concept is presented that aims to upcycle residual biomass by separating essential amino acids to be used for food and feed, and non-essential amino acids for production of bulk chemicals. PMID- 26132988 TI - PROGRESSION OF AGE-RELATED MACULAR DEGENERATION OVERLYING A LARGE CHOROIDAL VESSEL. AB - PURPOSE: To describe a patient who showed progression of age-related macular degeneration along the course of an underlying large choroidal vessel. METHODS: Retrospective case report. RESULTS: An 84-year-old woman was diagnosed with age related macular degeneration and followed for more than 6 years. Retinal pigment epithelial changes were more advanced in her right eye which had a thinner choroid than the fellow left eye. Multimodal imaging with swept-source optical coherence tomography showed that the progression of outer retinal and retinal pigment epithelial changes appeared to follow the course of a large choroidal vessel. CONCLUSION: The authors hypothesize that large choroidal vessels can compress the overlying choriocapillaris, possibly leading to outer retinal ischemia, which subsequently could focally accelerate the course of age-related macular degeneration. PMID- 26132987 TI - Synaptic ultrastructure changes in trigeminocervical complex posttrigeminal nerve injury. AB - Trigeminal nerves collecting sensory information from the orofacial area synapse on second-order neurons in the dorsal horn of subnucleus caudalis and cervical C1/C2 spinal cord (Vc/C2, or trigeminocervical complex), which is critical for sensory information processing. Injury to the trigeminal nerves may cause maladaptive changes in synaptic connectivity that plays an important role in chronic pain development. Here we examined whether injury to the infraorbital nerve, a branch of the trigeminal nerves, led to synaptic ultrastructural changes when the injured animals have developed neuropathic pain states. Transmission electron microscopy was used to examine synaptic profiles in Vc/C2 at 3 weeks postinjury, corresponding to the time of peak behavioral hypersensitivity following chronic constriction injury to the infraorbital nerve (CCI-ION). Using established criteria, synaptic profiles were classified as associated with excitatory (R-), inhibitory (F-), and primary afferent (C-) terminals. Each type was counted within the superficial dorsal horn of the Vc/C2 and the means from each rat were compared between sham and injured animals; synaptic contact length was also measured. The overall analysis indicates that rats with orofacial pain states had increased numbers and decreased mean synaptic length of R-profiles within the Vc/C2 superficial dorsal horn (lamina I) 3 weeks post-CCI-ION. Increases in the number of excitatory synapses in the superficial dorsal horn of Vc/C2 could lead to enhanced activation of nociceptive pathways, contributing to the development of orofacial pain states. PMID- 26132989 TI - Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung. AB - Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that has been traditionally characterized by incompletely reversible airflow limitation. Yet, the latter is poorly correlated with many other clinically relevant characteristics of the disease. Thus, the identification of biomarkers to more accurately assess this heterogeneity and disease severity may facilitate the discovery and development of new treatments and better management of patients with COPD. One molecule that has attracted attention as a potentially useful biomarker specifically for the emphysema subpopulation is the soluble receptor for advanced glycation end products (sRAGE). As the soluble isoform of a key proinflammatory signaling receptor, sRAGE acts as a "decoy" for RAGE ligands and prevents their interaction with the receptor. Multiple reports have now linked sRAGE to COPD, and more specifically to emphysema, and evidence is accumulating that this link is likely mechanistic in nature. Here we review the current state of knowledge about sRAGE biology, the mechanistic links to COPD, and the evidence for using it as a biomarker for emphysema. We also discuss sRAGE as a potential target for therapeutic intervention in COPD. PMID- 26132990 TI - Interactive effects of hypoxia, hypercapnia and lung volume on sympathetic nerve activity in humans. AB - NEW FINDINGS: What is the central question of this study? The central question of this study was to investigate the interaction of mild exposures to O2 and CO2 on chemoreflex control of SNA and the modulation of lung volume and respiratory phase on this interaction. What is the main finding and its importance? We demonstrate that the synergistic interaction of oxygen- and carbon dioxide chemosensitive control of the sympathetic nervous system with hypoxia and hypercapnia exists at very mild excitatory stimuli, is significantly overridden by lung inflation and does not extend to inhibitory modulation by hypocapnia in healthy subjects. These findings demonstrate the important inhibitory modulation of sympathetic nerve activity by lung inflation mechanisms in healthy individuals even in the presence of strong sympathoexcitatory stimuli. We hypothesized that simultaneous stimulation of O2 - and CO2 -sensitive chemoreflexes produces synergistic activation of the sympathetic nervous system and that this effect would be most apparent at low lung volume (expiratory) phases of respiration. Each subject (n = 11) breathed 16 gas mixtures in random order: a 4 * 4 matrix of normoxic to hypoxic (8, 12, 16 and 21% O2 ) combined with normocapnic to hypercapnic gases (0, 2, 4 and 6% CO2). Tidal volume, arterial pressure, heart rate and muscle sympathetic nerve activity (MSNA) were measured continuously before and while breathing each gas mixture for 2 min. Changes in MSNA were determined for each gas mixture. The MSNA was subdivided into low and high lung volume and respiratory phases to investigate further modulation by components of normal respiratory phase. Both hypoxia and hypercapnia increased mean MSNA independently. Mean and low lung volume MSNA increased exponentially with increasing levels of combined hypoxia and hypercapnia and resulted in a significant interaction (P < 0.01). In contrast, MSNA during the high lung volume phase of respiration never increased significantly (P > 0.4). Similar but less pronounced effects were found for expiratory and inspiratory phases of respiration. These effects created marked respiratory periodicity in MSNA at higher levels of combined hypoxia and hypercapnia. Finally, the response to hypoxia was not affected by hypocapnia, suggesting that the interaction occurs only during excitatory chemosensitive stimuli. These data indicate that hypoxia and hypercapnia interact to elicit synergistic sympathoexcitation and that withdrawal of sympathoinhibitory effects of lung inflation exaggerates this chemoreflex interaction. PMID- 26132991 TI - Effect of Stay-Green Wheat, a Novel Variety of Wheat in China, on Glucose and Lipid Metabolism in High-Fat Diet Induced Type 2 Diabetic Rats. AB - The use of natural hypoglycemic compounds is important in preventing and managing Type 2 diabetes mellitus (T2DM). Forty male Sprague-Dawley rats weighing 150-180 g were divided into four groups to investigate the effects of the compounds in stay-green wheat (SGW), a novel variety of wheat in China, on T2DM rats. The control group (NDC) was fed with a standard diet, while T2DM was induced in the rats belonging to the other three groups by a high-fat diet followed by a streptozotocin (STZ) injection. The T2DM rats were further divided into a T2DM control group (DC), which was fed with the normal diet containing 50% common wheat flour, a high dose SGW group (HGW) fed with a diet containing 50% SGW flour, and a low dose SGW group (LGW) fed with a diet containing 25% SGW flour and 25% common wheat flour. Our results showed that SGW contained cereal antioxidants, particularly high in flavonoids and anthocyanins (46.14 +/- 1.80 mg GAE/100 g DW and 1.73 +/- 0.14 mg CGE/100 g DW, respectively). Furthermore, SGW exhibited a strong antioxidant activity in vitro (30.33 +/- 2.66 MUg TE/g DW, p < 0.01). Administration of the SGW at a high and low dose showed significant down regulatory effects on fasting blood glucose (decreasing by 11.3% and 7.0%, respectively), insulin levels (decreasing by 12.3% and 9.7%, respectively), and lipid status (decreasing by 9.1% and 7.5%, respectively) in T2DM rats (p < 0.01). In addition, the T2DM groups treated with SGW at a high and low dose showed a significant increase in the blood superoxide dismutase (1.17 fold and 1.15 fold, respectively) and glutathione peroxidase activities (1.37 fold and 1.30 fold, respectively) compared with the DC group (p < 0.01). The normalized impaired antioxidant status of the pancreatic islet and of the liver compared with the DC group was also significantly increased. Our results indicated that SGW components exerting a glycemic control and a serum lipid regulation effect may be due to their free radical scavenging capacities to reduce the risk of T2DM in experimental diabetic rats. PMID- 26132992 TI - Impact of Weight Loss on Plasma Leptin and Adiponectin in Overweight-to-Obese Post Menopausal Breast Cancer Survivors. AB - Women who are obese at the time of breast cancer diagnosis have higher overall mortality than normal weight women and some evidence implicates adiponectin and leptin as contributing to prognostic disadvantage. While intentional weight loss is thought to improve prognosis, its impact on these adipokines is unclear. This study compared the pattern of change in plasma leptin and adiponectin in overweight-to-obese post-menopausal breast cancer survivors during weight loss. Given the controversies about what dietary pattern is most appropriate for breast cancer control and regulation of adipokine metabolism, the effect of a low fat versus a low carbohydrate pattern was evaluated using a non-randomized, controlled study design. Anthropometric data and fasted plasma were obtained monthly during the six-month weight loss intervention. While leptin was associated with fat mass, adiponectin was not, and the lack of correlation between leptin and adiponectin concentrations throughout weight loss implies independent mechanisms of regulation. The temporal pattern of change in leptin but not adiponectin was affected by magnitude of weight loss. Dietary pattern was without effect on either adipokine. Mechanisms not directly related to dietary pattern, weight loss, or fat mass appear to play dominant roles in the regulation of circulating levels of these adipokines. PMID- 26132993 TI - A Systematic Review of the Efficacy of Bioactive Compounds in Cardiovascular Disease: Phenolic Compounds. AB - The prevalence of cardiovascular diseases (CVD) is rising and is the prime cause of death in all developed countries. Bioactive compounds (BAC) can have a role in CVD prevention and treatment. The aim of this work was to examine the scientific evidence supporting phenolic BAC efficacy in CVD prevention and treatment by a systematic review. Databases utilized were Medline, LILACS and EMBASE, and all randomized controlled trials (RCTs) with prospective, parallel or crossover designs in humans in which the effects of BAC were compared with that of placebo/control were included. Vascular homeostasis, blood pressure, endothelial function, oxidative stress and inflammatory biomarkers were considered as primary outcomes. Cohort, ecological or case-control studies were not included. We selected 72 articles and verified their quality based on the Scottish Intercollegiate Guidelines Network, establishing diverse quality levels of scientific evidence according to two features: the design and bias risk of a study. Moreover, a grade of recommendation was included, depending on evidence strength of antecedents. Evidence shows that certain polyphenols, such as flavonols can be helpful in decreasing CVD risk factors. However, further rigorous evidence is necessary to support the BAC effect on CVD prevention and treatment. PMID- 26132995 TI - Expanding the WHO list of essential medicines for children: A call for further action. PMID- 26132997 TI - POTENTIAL PLACE OF SGLT2 INHIBITORS IN TREATMENT PARADIGMS FOR TYPE 2 DIABETES MELLITUS. AB - OBJECTIVE: Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms. METHODS: The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin. RESULTS: Evidence from clinical trials in patients with T2DM supports the use of SGLT2 inhibitors either as monotherapy or in addition to other glucose-lowering treatments as adjuncts to diet and exercise, and we have gained significant clinical experience in a relatively short time. CONCLUSION: The drugs appear to be useful in a variety of T2DM populations, contingent primarily on renal function. Most obviously, SGLT2 inhibitors appear to be well suited for patients with potential for hypoglycemia or weight gain. In clinical trials, patients treated with SGLT2 inhibitors have experienced moderate weight loss and a low risk of hypoglycemic events except when used in combination with an insulin secretagogue. In addition, SGLT2 inhibitors have been shown to reduce blood pressure, so they may be beneficial in patients with T2DM complicated by hypertension. SGLT2 inhibitors were incorporated into the 2015 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia and received an even more prominent position in the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive diabetes management guidelines and algorithm. PMID- 26132998 TI - Incidence of geriatric hip fractures in Tasmania 2011-2012. PMID- 26132994 TI - Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity. AB - Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with L-arginine supplementation exhibited less consistent results; however, L-citrulline, the precursor of L-arginine, may be a promising alternative. In this study, we determined the effects of L-citrulline compared to L-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with L-citrulline or L-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. L arginine and L-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that L-citrulline, and not L-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues. PMID- 26132999 TI - Dual-Size Silicon Nanocrystal-Embedded SiO(x) Nanocomposite as a High-Capacity Lithium Storage Material. AB - SiOx-based materials attracted a great deal of attention as high-capacity Li(+) storage materials for lithium-ion batteries due to their high reversible capacity and good cycle performance. However, these materials still suffer from low initial Coulombic efficiency as well as high production cost, which are associated with the complicated synthesis process. Here, we propose a dual-size Si nanocrystal-embedded SiOx nanocomposite as a high-capacity Li(+) storage material prepared via cost-effective sol-gel reaction of triethoxysilane with commercially available Si nanoparticles. In the proposed nanocomposite, dual-size Si nanocrystals are incorporated into the amorphous SiOx matrix, providing a high capacity (1914 mAh g(-1)) with a notably improved initial efficiency (73.6%) and stable cycle performance over 100 cycles. The highly robust electrochemical and mechanical properties of the dual-size Si nanocrystal-embedded SiOx nanocomposite presented here are mainly attributed to its peculiar nanoarchitecture. This study represents one of the most promising routes for advancing SiOx-based Li(+) storage materials for practical use. PMID- 26133000 TI - Factors Associated with Incomplete Bladder Emptying in Older Women with Overactive Bladder Symptoms. AB - OBJECTIVES: To identify factors associated with incomplete bladder emptying in older women with overactive bladder (OAB) symptoms. DESIGN: Retrospective medical records review. SETTING: Urodynamic laboratory at a large academic health care system in the southeast United States. PARTICIPANTS: Medical records from women aged 65 and older who presented to clinic with OAB symptoms and who had completed outpatient urodynamic testing (N = 203). MEASUREMENTS: Three cutoff values of postvoid residual (PVR) volume (100, 150, 200 mL) were created a priori to classify incomplete bladder emptying. Age; vaginal parity; diabetes mellitus (DM); and a history of cerebrovascular accident, back surgery or injury, pelvic surgery, anti-urinary incontinence surgery, and pelvic organ prolapse were included in univariate and multivariate logistic regression models to determine factors associated with incomplete bladder emptying. RESULTS: When PVR volume of 200 mL or greater was used to define incomplete bladder emptying, history of back surgery or injury (odds ratio (OR) = 4.30, 95% confidence interval (CI) = 1.16 15.91) and pelvic surgery (OR = 4.42, 95% CI = 1.51-12.95) were significantly associated with incomplete bladder emptying in multivariate analysis. No factors were significantly associated with PVR volumes of 100 mL or greater or 150 mL or greater. CONCLUSION: PVR volumes should be assessed in older women with OAB symptoms and a history of back surgery or injury or pelvic surgery, especially before the administration of antimuscarinic medications. Caution in interpreting these findings is needed because PVR volumes obtained from pressure-flow studies may differ from those obtained from natural voiding. Lack of data on medications that can contribute to incomplete bladder emptying and the small number of women with cerebrovascular accident, back surgery or injury, and DM may have influenced the results. PMID- 26133003 TI - The Multidimensional Nature of Relationships: The Perceptions of Iranian Nursing Students and Educators of the Student-Educator Relationship. AB - BACKGROUND: The student-educator relationship in nursing is very important to the success of teaching and learning. The perceptions of students and educators of this relationship affect its success. Therefore, it is necessary to better understand this relationship. PURPOSE: The purpose of the current study was to explore Iranian nursing students' and educators' perceptions of student-educator relationship in clinical nursing education. METHODS: In this conventional content analysis study, eight Bachelor of Nursing students and 10 clinical nursing educators from nursing and midwifery school in Mashhad (Iran) participated. Purposive sampling was used to select participants. Data were gathered using semistructured interviews. To analyze data, a conventional content analysis approach was used to identify meaning units and their condensation and to make codes and create categories RESULTS: : Results showed that the multidimensional nature of the student-educator relationship in clinical nursing education consists of (a) dimensions related to the educator, (b) dimensions related to the student, and (c) dimensions of relationship quality. Each of these categories is composed of codes that showed the perception of participants about the nature of relationship. CONCLUSIONS: On the basis of the unique features and attributes regarding relationship perceptions in clinical nursing education identified among the participants of this study, students and educators in Iran should pay greater attention to establishing the relationship as it relates to these attributes. PMID- 26133004 TI - Analysis of the Issues and Needs of Parents of Children With Developmental Disabilities in Japan Using Focus Group Interviews. AB - BACKGROUND: The number of Japanese children with developmental disabilities (DDs) has seen a steady increase in recent years. The parents and families of children with DD experience distress both at the time of DD diagnosis and afterward. AIM: This study aimed to elucidate the issues and needs of the parents of children with DD to facilitate the development of effective support strategies necessary to help the family handle the special needs of their child with DD. METHODS: Japanese-speaking parents with children who were aged 3-14 years and currently being treated in a hospital for DDs were invited to participate in one of three focus groups. A trained moderator led each 90-minute audio-recorded group using a semistructured interview guide. All transcripts were coded using thematic content analysis. RESULTS: Six categories of parents' significant issues were identified, with three of the categories classified as critical needs. CONCLUSIONS: The issues and needs identified in this study are useful for developing an effective family support program and a related performance framework. Key concerns include providing relevant information support, providing counseling and consultation support for parents and siblings, and providing resources to children with DD that are necessary to help them deal effectively with their disabilities. PMID- 26133007 TI - Fibromyalgia incidence among patients with hepatitis B infection. AB - AIM: The purpose of our investigation was to evaluate the incidence of fibromyalgia syndrome (FMS) and identify FMS-related clinical symptoms in hepatitis B virus (HBV) patients. METHODS: One hundred and eighteen HBV surface antigen (HbsAg)-positive patients (40 with chronic active hepatitis B, 40 hepatitis B carriers and 38, all of whom had been antiretroviral-treated for at least 3 months) were included in this study. In addition, 60 age- and gender matched HbsAg-negative healthy controls were included in the study. RESULTS: There was no significant difference in age, gender or body mass index (BMI) between the two groups (P > 0.05). Serum aspartate aminotransferase and alanine aminotransferase levels were significantly higher in HBV patients relative to the control group (P < 0.05). The incidence of FMS, widespread body pain, fatigue, sleep disturbance, anxiety, morning stiffness, arthralgia was significantly greater among HBV patients relative to the control group. Additionally, the mean tender point counts and the visual analog scale values were significantly higher among the HBV patients (P < 0.05). CONCLUSIONS: The results of the present study demonstrate that FMS incidence is greater among HBV patients relative to control subjects. However, there were no differences in FMS incidence among the subgroups of HBV diagnoses. PMID- 26133008 TI - Bayesian Source Attribution of Salmonellosis in South Australia. AB - Salmonellosis is a significant cause of foodborne gastroenteritis in Australia, and rates of illness have increased over recent years. We adopt a Bayesian source attribution model to estimate the contribution of different animal reservoirs to illness due to Salmonella spp. in South Australia between 2000 and 2010, together with 95% credible intervals (CrI). We excluded known travel associated cases and those of rare subtypes (fewer than 20 human cases or fewer than 10 isolates from included sources over the 11-year period), and the remaining 76% of cases were classified as sporadic or outbreak associated. Source-related parameters were included to allow for different handling and consumption practices. We attributed 35% (95% CrI: 20-49) of sporadic cases to chicken meat and 37% (95% CrI: 23-53) of sporadic cases to eggs. Of outbreak-related cases, 33% (95% CrI: 20-62) were attributed to chicken meat and 59% (95% CrI: 29-75) to eggs. A comparison of alternative model assumptions indicated that biases due to possible clustering of samples from sources had relatively minor effects on these estimates. Analysis of source-related parameters showed higher risk of illness from contaminated eggs than from contaminated chicken meat, suggesting that consumption and handling practices potentially play a bigger role in illness due to eggs, considering low Salmonella prevalence on eggs. Our results strengthen the evidence that eggs and chicken meat are important vehicles for salmonellosis in South Australia. PMID- 26133009 TI - Longitudinal Associations Between Metabolic Syndrome Components and Telomere Shortening. AB - CONTEXT: Deterioration of metabolic syndrome (MetS) has been associated with short telomere length (TL). Large-scale longitudinal studies with repeated measures of MetS and TL are lacking. OBJECTIVES: We examined whether baseline MetS components predict TL over time, and whether deteriorations in MetS parallel telomere attrition. DESIGN AND SETTING: Participants were part of The Netherlands Study of Depression and Anxiety, an ongoing prospective cohort study. PARTICIPANTS: This study included 1808 participants age 18-65 years. MAIN OUTCOME MEASURES: Leukocyte TL (using qPCR) and MetS components (waist circumference, triglycerides, high-density lipoprotein [HDL] cholesterol, systolic blood pressure, and fasting glucose) were determined at baseline and after 6 years. Generalized estimated equation models were used to examine the associations between baseline MetS and TL over time, and linear regressions were used to associate 6-year changes in both MetS components and TL, while adjusting for sociodemographic and lifestyle factors. RESULTS: Higher baseline waist circumference (B = -29.7; P = .006) and glucose (B = -26.4; P = .02), and lower HDL (B = 25.5; P = .03) were consistently associated with shorter TL over followup. Greater 6-year increase in waist circumference was associated with larger telomere attrition (B = -41.8; P = .01), and similar but nonsignificant associations were observed for larger increase in triglycerides and glucose levels. CONCLUSIONS: Metabolic dysregulations are associated with shorter telomeres over two time points. In particular, increasing abdominal adiposity is accompanied by accelerated telomere attrition. Future studies should elucidate underlying mechanisms of this bidirectional relationship and investigate whether targeting obesity may reduce telomere attrition to prevent further deterioration toward cardiovascular and aging-related complications. PMID- 26133010 TI - Lessons from modENCODE. AB - The modENCODE (Model Organism Encyclopedia of DNA Elements) Consortium aimed to map functional elements-including transcripts, chromatin marks, regulatory factor binding sites, and origins of DNA replication-in the model organisms Drosophila melanogaster and Caenorhabditis elegans. During its five-year span, the consortium conducted more than 2,000 genome-wide assays in developmentally staged animals, dissected tissues, and homogeneous cell lines. Analysis of these data sets provided foundational insights into genome, epigenome, and transcriptome structure and the evolutionary turnover of regulatory pathways. These studies facilitated a comparative analysis with similar data types produced by the ENCODE Consortium for human cells. Genome organization differs drastically in these distant species, and yet quantitative relationships among chromatin state, transcription, and cotranscriptional RNA processing are deeply conserved. Of the many biological discoveries of the modENCODE Consortium, we highlight insights that emerged from integrative studies. We focus on operational and scientific lessons that may aid future projects of similar scale or aims in other, emerging model systems. PMID- 26133011 TI - Engineering of parallel plasmonic-photonic interactions for on-chip refractive index sensors. AB - Ultra-narrow linewidth in the extinction spectrum of noble metal nanoparticle arrays induced by the lattice plasmon resonances (LPRs) is of great significance for applications in plasmonic lasers and plasmonic sensors. However, the challenge of sustaining LPRs in an asymmetric environment greatly restricts their practical applications, especially for high-performance on-chip plasmonic sensors. Herein, we fully study the parallel plasmonic-photonic interactions in both the Au nanodisk arrays (NDAs) and the core/shell SiO2/Au nanocylinder arrays (NCAs). Different from the dipolar interactions in the conventionally studied orthogonal coupling, the horizontal propagating electric field introduces the out of-plane "hot spots" and results in electric field delocalization. Through controlling the aspect ratio to manipulate the "hot spot" distributions of the localized surface plasmon resonances (LSPRs) in the NCAs, we demonstrate a high performance refractive index sensor with a wide dynamic range of refractive indexes ranging from 1.0 to 1.5. Both high figure of merit (FOM) and high signal to-noise ratio (SNR) can be maintained under these detectable refractive indices. Furthermore, the electromagnetic field distributions confirm that the high FOM in the wide dynamic range is attributed to the parallel coupling between the superstrate diffraction orders and the height-induced LSPR modes. Our study on the near-field "hot-spot" engineering and far-field parallel coupling paves the way towards improved understanding of the parallel LPRs and the design of high performance on-chip refractive index sensors. PMID- 26133012 TI - The Impact of Diagnostic Changes on the Rise in Thyroid Cancer Incidence: A Population-Based Study in Selected High-Resource Countries. AB - BACKGROUND: Thyroid cancer (TC) incidence is rising in many countries, but the corresponding mortality is constant or declining. Incidence increases appear largely restricted to small papillary TC in young/middle-age individuals. We compared age-specific incidence rates across countries and time periods in order to estimate the fraction of TC possibly attributable to increased surveillance of the thyroid gland (diagnostic changes) following the introduction of neck ultrasonography in the 1980s. METHODS: We focused on high-resource countries, including four Nordic countries, England and Scotland, France, Italy, the United States, Australia, Japan, and the Republic of Korea. Before the 1970s, TC incidence in Nordic countries increased proportionally to the second power of age, consistent with the multistage model of carcinogenesis. Using this historical observation for reference, we attributed the progressive departure from linearity of the age curves in each country to an increased detection of asymptomatic disease in young/middle-age individuals. The proportion of cases attributable to diagnostic changes was estimated from the difference between observed rates and those expected using the Nordic countries as reference. RESULTS: Diagnostic changes may account for >=60% of TC cases diagnosed in 2003 2007 in women aged under 80 years in France, Italy, the United States, Australia, and the Republic of Korea, and approximately 50% in other assessed countries, except Japan (30%). The proportions attributable to diagnostic changes were higher in countries with largest incidence increases and were consistent across sexes, although increases were smaller and delayed in men. CONCLUSIONS: A large proportion of TC cases diagnosed in high-resource countries in the last two decades are likely to be due to diagnostic changes. This proportion has progressively increased over time, and it is likely to grow further in the future. Since there is evidence of harm but no proof of benefit from the intense scrutiny of the thyroid, the dangers of overdiagnosis and overtreatment of TC should be urgently addressed. PMID- 26133013 TI - Flirtation reduces males' fecundity but not longevity. AB - Theory predicts that due to limited resources males should strategically adjust their investment in reproduction and survival. Based on different conceptual framework, experimental designs, and study species, many studies support while others contradict this general prediction. Using a moth Ephestia kuehniella whose adults do not feed and thus have fixed resources for their lifetime fitness, we investigated whether males adjusted their investment in various life activities under dynamic socio-sexual environment. We allowed focal males to perceive rivals or additional females without physical contact. We show that males do not adjust the number of sperm they transfer to mates in a given copulation at different immediate or both immediate and mean sperm competition levels. Contradictory to general predictions, our results demonstrate that cues from additional females increase males' investment in courtship and reduce their lifetime number of copulations and sperm ejaculated, whereas cues from rivals have no effect on these parameters. Males have similar longevity in all treatments. We suggest that the sex pheromone produced by multiple females overstimulate males, increasing males' costly flirtations, and reducing their lifetime copulation frequency and fecundity. This finding offers a novel explanation for the success of mating disruption strategy using sex pheromones in pest management. PMID- 26133014 TI - A case of bilateral macrodontia of mandibular second premolars from a Chalcolithic context in the Iberian Peninsula. AB - Isolated macrodontia, consisting of the gigantism of a single tooth, is an extremely rare condition. Only 16 cases of isolated macrodontia of mandibular second premolars have been reported to date. Although the aetiology of this phenomenon remains unknown, many authors have related it to the control of the apoptotic process, leading to the patterning and size of dental cusps. There is not a clear genetic inheritance pattern since only two of those 16 cases correspond to close relatives. To our knowledge, there have been no reports of isolated macrodontia of mandibular second premolars in archaeological remains. Cova del Panta de Foix site is a Chalcolithic sepulchral cave situated in the North-East of the Iberian Peninsula in which the remains of at least 30 individuals were recovered. Most of these individuals show several signs of environmental stressors. The current study presents the first case of isolated bilateral macrodontia of mandibular premolars from an archaeological context, corresponding to a young male individual discovered in this site. This condition could be the last consequence of environmental factors epigenetically affecting apoptosis processes in early tooth development and a possible genetic predisposition to show a shape-deviation in the dentition. PMID- 26133016 TI - Toward the Healthiest Symbiosis. PMID- 26133015 TI - Inhibitory killer cell immunoglobulin-like receptor (iKIR) mismatches improve survival after T-cell-repleted haploidentical transplantation. AB - Alloreactivity triggered by interaction between killer cell immunoglobulin-like receptors (KIRs) and natural killer (NK) cells plays a role in the graft-versus tumor effect after hematopoietic stem cell transplantation (SCT). Our aim in this study was to evaluate this role in the setting of T-cell-repleted haploidentical SCT with postinfusion high-dose cyclophosphamide (PT-Cy). We included 33 patients. Among patient-donor pairs with at least 1 inhibitory KIR (iKIR) gene mismatch, event-free survival (EFS) and cumulative incidence of relapse 1 year after transplant were significantly better (85% vs. 37% [P = 0.008] and 18% vs. 46% [P = 0.041], respectively). A subanalysis in 12 patients with Hodgkin's lymphoma (HL) showed an improvement in EFS 1 year after transplant in those patients with KIR ligand mismatch (100% vs. 25%, P = 0.012), although overall survival (OS) was not affected (85% vs. 80%, P = 0.2). Eight of 12 patient-donors pairs presented iKIR mismatches. Of note, this outcome was better in the small subgroup, both for EFS (100% vs. 25%, P = 0.012) and for OS (100% vs. 37%, P = 0.004). Our data suggest that in the setting of T-cell-repleted haploidentical SCT with PT-Cy, iKIR mismatch is associated with improved survival, with particularly good results for both iKIR and KIR ligand mismatches in patients with HL. PMID- 26133017 TI - Four super water-stable lanthanide-organic frameworks with active uncoordinated carboxylic and pyridyl groups for selective luminescence sensing of Fe(3.). AB - Four super water-stable isostructural lanthanide-organic frameworks, [Ln(HL)(H2O)2]n.2H2O (1-Ln) (Ln = Eu, Tb, Nd and Sm), have been successfully synthesized under hydrothermal conditions with 3,5-di(2,4 dicarboxylphenyl)pyridine (H4L) and Ln(NO3)3.6H2O. 1-Ln shows a novel 2D layered structure with uncoordinated carboxylic and pyridyl groups pointing to the interior of interlayer channels. The luminescent properties of 1-Eu in the solid state and one steeped in aqueous solution have been measured, which show excellent luminescence and good luminescent stability in water. Next 1-Eu was chosen as a probe for sensing different metal ions. Consequently, 1-Eu exhibits a highly selective response to Fe(3+) through the luminescence quenching effect in aqueous solutions. The probable mechanisms of the quenching effects have been investigated in detail. PMID- 26133018 TI - "Crude Vaccine Effectiveness" Is a Misleading Term in Test-negative Studies of Influenza Vaccine Effectiveness. PMID- 26133019 TI - Lies, Damned Lies, and Health Inequality Measurements: Understanding the Value Judgments. AB - Measuring and monitoring socioeconomic health inequalities are critical for understanding the impact of policy decisions. However, the measurement of health inequality is far from value neutral, and one can easily present the measure that best supports one's chosen conclusion or selectively exclude measures. Improving people's understanding of the often implicit value judgments is therefore important to reduce the risk that researchers mislead or policymakers are misled. While the choice between relative and absolute inequality is already value laden, further complexities arise when, as is often the case, health variables have both a lower and upper bound, and thus can be expressed in terms of either attainments or shortfalls, such as for mortality/survival.We bring together the recent parallel discussions from epidemiology and health economics regarding health inequality measurement and provide a deeper understanding of the different value judgments within absolute and relative measures expressed both in attainments and shortfalls, by graphically illustrating both hypothetical and real examples. We show that relative measures in terms of attainments and shortfalls have distinct value judgments, highlighting that for health variables with two bounds the choice is no longer only between an absolute and a relative measure but between an absolute, an attainment- relative and a shortfall-relative one. We illustrate how these three value judgments can be combined onto a single graph which shows the rankings according to all three measures, and illustrates how the three measures provide ethical benchmarks against which to judge the difference in inequality between populations. PMID- 26133020 TI - Commentary: Value Judgments in Health Inequality Measurement. PMID- 26133021 TI - Brief Report: Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection. AB - BACKGROUND: Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period. METHODS: We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome coronavirus, using data from the epidemic in 2003 in Hong Kong. RESULTS: We estimated the incubation period of severe acute respiratory syndrome based on a subset of patients with available data on exposure periods and a separate subset of patients in a putative common source outbreak, and we found associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders. CONCLUSIONS: Our findings suggest that patients with a shorter incubation period went on to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association. PMID- 26133022 TI - Brief Report: Databases in the Asia-Pacific Region: The Potential for a Distributed Network Approach. AB - BACKGROUND: This study describes the availability and characteristics of databases in Asian-Pacific countries and assesses the feasibility of a distributed network approach in the region. METHODS: A web-based survey was conducted among investigators using healthcare databases in the Asia-Pacific countries. Potential survey participants were identified through the Asian Pharmacoepidemiology Network. RESULTS: Investigators from a total of 11 databases participated in the survey. Database sources included four nationwide claims databases from Japan, South Korea, and Taiwan; two nationwide electronic health records from Hong Kong and Singapore; a regional electronic health record from western China; two electronic health records from Thailand; and cancer and stroke registries from Taiwan. CONCLUSIONS: We identified 11 databases with capabilities for distributed network approaches. Many country-specific coding systems and terminologies have been already converted to international coding systems. The harmonization of health expenditure data is a major obstacle for future investigations attempting to evaluate issues related to medical costs. PMID- 26133023 TI - The Authors Respond. PMID- 26133024 TI - Dietary Patterns and Cognitive Decline Among Chinese Older Adults. AB - BACKGROUND: Prospective evidence of associations of dietary patterns with cognitive decline is limited and inconsistent. We examined how cognitive changes among Chinese older adults relate to either an adapted Mediterranean diet score or factor analysis-derived dietary patterns. METHODS: This prospective cohort study comprised 1,650 adults >=55 years of age, who completed a cognitive screening test at two or more waves of the China Health and Nutrition Survey in 1997, 2000, or 2004. Outcomes were repeated measures of global cognitive scores, composite cognitive z scores (standardized units [SU]), and standardized verbal memory scores (SU). Baseline diet was measured by 24-hour recalls over 3 days. We used linear mixed effects models to evaluate how changes in cognitive scores were associated with adapted Mediterranean diet score and two dietary pattern scores derived from factor analysis. RESULTS: Among adults >=65 years of age, compared with participants in the lowest tertile of adapted Mediterranean diet, those in the highest tertile had a slower rate of cognitive decline (difference in mean SU change/year beta = 0.042; 95% confidence interval [CI]: 0.002, 0.081). A wheat based diverse diet derived by factor analysis shared features of the adapted Mediterranean diet, with the top tertile associated with slower annual decline in global cognitive function (beta = 0.069 SU/year; 95% CI: 0.023, 0.114). We observed no associations among adults <65 years of age. CONCLUSIONS: Our findings suggest that an adapted Mediterranean diet or a wheat-based, diverse diet with similar components may reduce the rate of cognitive decline in later life in the Chinese population. PMID- 26133025 TI - Review Article: The Fraction of Influenza Virus Infections That Are Asymptomatic: A Systematic Review and Meta-analysis. AB - BACKGROUND: The fraction of persons with influenza virus infection, who do not report any signs or symptoms throughout the course of infection is referred to as the asymptomatic fraction. METHODS: We conducted a systematic review and meta analysis of published estimates of the asymptomatic fraction of influenza virus infections. We found that estimates of the asymptomatic fraction were reported from two different types of studies: first, outbreak investigations with short term follow-up of potentially exposed persons and virologic confirmation of infections; second, studies conducted across epidemics typically evaluating rates of acute respiratory illness among persons with serologic evidence of infection, in some cases adjusting for background rates of illness from other causes. RESULTS: Most point estimates from studies of outbreak investigations fell in the range 4%-28% with low heterogeneity (I = 0%) with a pooled mean of 16% (95% confidence interval = 13%, 19%). Estimates from the studies conducted across epidemics without adjustment were very heterogeneous (point estimates 0%-100%; I = 97%), while estimates from studies that adjusted for background illnesses were more consistent with point estimates in the range 65%-85% and moderate heterogeneity (I = 58%). Variation in estimates could be partially explained by differences in study design and analysis, and inclusion of mild symptomatic illnesses as asymptomatic in some studies. CONCLUSIONS: Estimates of the asymptomatic fraction are affected by the study design, and the definitions of infection and symptomatic illness. Considerable differences between the asymptomatic fraction of infections confirmed by virologic versus serologic testing may indicate fundamental differences in the interpretation of these two indicators. PMID- 26133026 TI - Interactions Between Air Pollution and Obesity on Blood Pressure and Hypertension in Chinese Children. AB - BACKGROUND: Little information exists regarding the effect of interaction of obesity and long-term air pollution exposure on children's blood pressure and hypertension in areas with high levels of air pollution. The aim of this study is to assess effect modification by obesity on the association between exposure and blood pressure in Chinese children. METHODS: We studied 9,354 Chinese children, ages 5-17 years old, from 24 elementary schools and 24 middle schools in the Seven Northeastern Cities during 2012-2013. Four-year average concentrations of particles with an aerodynamic diameter <=10 um (PM10), sulfur dioxide, nitrogen dioxides, and ozone (O3) were measured at the monitoring stations in the 24 districts. We used generalized additive models and two-level logistic regression models to examine the health effects. RESULTS: Consistent interactions were found between exposure and obesity on blood pressure and hypertension. The association between exposure and hypertension was consistently larger for overweight/obese children than for children with normal-weight, with odds ratios for hypertension ranging from 1.16 per 46.3MUg/m for O3 (95% confidence interval [CI] = 1.12, 1.20) to 2.91 per 30.6MUg/m for PM10 (95% CI = 2.32, 3.64), and estimated increases in mean systolic and diastolic blood pressure ranging from 0.57 mmHg (95% CI = 0.36, 0.78) and 0.63 mmHg (95% CI = 0.46, 0.81) per 46.3 MUg/m for O3 to 4.04 mmHg (95% CI = 3.00, 5.09) and 2.02 mmHg (95% CI = 1.14, 2.89) per 23.4 MUg/m for sulfur dioxide. CONCLUSIONS: Obesity amplifies the association of long term air pollution exposure with blood pressure and hypertension in Chinese children. PMID- 26133027 TI - Shedding light on cell cycle control by T and B lymphocytes. PMID- 26133028 TI - Retraction: Hyaluronan activation of the Nlrp3 inflammasome contributes to the development of airway hyperresponsiveness. PMID- 26133029 TI - Targeted Activation of Toll-Like Receptors: Conjugation of a Toll-Like Receptor 7 Agonist to a Monoclonal Antibody Maintains Antigen Binding and Specificity. AB - Therapeutic activation of Toll-like receptors (TLR) has potential for cancer immunotherapy, for augmenting the activity of antitumor monoclonal antibodies (mAbs), and for improved vaccine adjuvants. A previous attempt to specifically target TLR agonists to dendritic cells (DC) using mAbs failed because conjugation led to nonspecific binding and mAbs lost specificity. We demonstrate here for the first time the successful conjugation of a small molecule TLR7 agonist to an antitumor mAb (the anti-hCD20 rituximab) without compromising antigen specificity. The TLR7 agonist UC-1V150 was conjugated to rituximab using two conjugation methods, and yield, molecular substitution ratio, retention of TLR7 activity, and specificity of antigen binding were compared. Both conjugation methods produced rituximab-UC-1V150 conjugates with UC-1V150: rituximab ratio ranging from 1:1 to 3:1 with drug loading quantified by UV spectroscopy and drug substitution ratio verified by MALDI TOF mass spectroscopy. The yield of purified conjugates varied with conjugation method and dropped as low as 31% using a method previously described for conjugating UC-1V150 to proteins, where a bifunctional cross-linker was first reacted with rituximab and second to the TLR7 agonist. We therefore developed a direct conjugation method by producing an amine reactive UV active version of UC-1V150, termed NHS:UC-1V150. Direct conjugation with NHS:UC-1V150 was quick and simple and gave improved conjugate yields of 65 78%. Rituximab-UC-1V150 conjugates had the expected pro-inflammatory activity in vitro (EC50 28-53 nM) with a significantly increased activity over unconjugated UC-1V150 (EC50 547 nM). Antigen binding and specificity of the rituxuimab-UC 1V150 conjugates was retained, and after incubation with human peripheral blood leukocytes, all conjugates bound strongly only to CD20-expressing B cells while no nonspecific binding to CD20-negative cells was observed. Selective targeting of Toll-like receptor activation directly within tumors or to DC is now feasible. PMID- 26133030 TI - Effect of micronized cellulose powder on the efficacy of topical oxymetazoline in allergic rhinitis. AB - BACKGROUND: Defective nasal barrier function is implicated in allergic rhinitis, which results in persistent inflammation and clinical symptoms, among which congestion plays a prominent role. In searching ways to improve the efficacy of nasally applied drugs in this condition, we tested the hypothesis that hydroxypropylmethylcellulose (HPMC), known as a mucoprotective agent, could enhance the efficacy of a decongestant (oxymetazoline nasal spray, 0.05%) by "sealing" it to the mucosa. METHODS: This double-blind placebo-controlled study was conducted with 40 patients (mean age, 35 years; 23 women) with persistent allergic rhinitis. The patients were randomized to receive 1 puff of oxymetazoline, followed by 1 puff of either HPMC or lactose powder (placebo) twice a day for 7 days and then only oxymetazoline rescue medication for another week. Peak inspiratory nasal flow (PNIF) was measured for 360 minutes after oxymetazoline and HPMC or placebo insufflation on days 1 and 8, and at a single point on day 15. Symptoms assessments involve visual analog scales and total nasal symptom scores. RESULTS: HPMC significantly enhanced oxymetazoline increased PNIF at days 1 (p = 0.042) and 8 (p = 0.006). Baseline PNIF was greater in the HPMC group at day 15 (p = 0.014), indicative of further reduced nasal congestion. All nasal symptoms improved in both groups at day 8, but only the HPMC group showed further amelioration at day 15. Rescue medication was smaller in the HPMC group between days 8 and 15. CONCLUSION: HPMC enhances decongestion through mucoadhesion but may also be augmenting the mucosal barrier in allergic rhinitis, which explains the carryover efficacy of oxymetazoline for a week after its discontinuation. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01986582. PMID- 26133037 TI - Beneficial Effects of Red Yeast Rice on High-Fat Diet-Induced Obesity, Hyperlipidemia, and Fatty Liver in Mice. AB - Obesity is a common cause of hyperlipidemia, which is a major coronary risk factor. Previous studies have shown red yeast rice (RYR) effectiveness in lowering low-density lipoprotein cholesterol. The aim of this study was to investigate the effects of RYR on obesity and hyperlipidemia. Mice were randomly separated into five groups: the control group with a normal diet, the high-fat diet (HFD) group fed a HFD without any treatment, and HFD-fed groups supplemented with RYR (1 g/kg/day for 8 weeks, 1 g/kg/day for 12 weeks, and 2.5 g/kg/day for 8 weeks). Body weight was recorded twice and food intake thrice weekly. Liver and fat pads were surgically removed and weighed. The levels of lipid parameters, liver enzymes, and leptin levels were measured. The HFD feeding resulted in obesity, which was associated with increases in body weight, liver weight, fat pad weight, liver enzymes, and plasma leptin levels with the development of hyperlipidemia. RYR prevented weight gain and fat pad weight in mice fed a HFD. RYR alleviated blood lipid parameters, liver enzymes, and leptin levels, and improved atherogenic index. These findings suggest that RYR has therapeutic potential in treating obesity and hyperlipidemia. PMID- 26133038 TI - Experiences of Families Transmitting Values in a Rapidly Changing Society: Implications for Family Therapists. AB - Intergenerational value transmission affects parent-child relationships and necessitates constant negotiation in families. Families with adolescents from rapidly changing societies face unique challenges in balancing the traditional collectivistic family values that promote harmony with emerging values that promote autonomy. Using modern Turkey as an example of such a culture, the authors examine the transmission process in families that hold more traditional and collectivistic values than their adolescent children. Special consideration is given to generational and cultural differences in the autonomy and relatedness dimensions. PMID- 26133039 TI - Molecular Pac-Man and Tacos: layered Cu(II) cages from ligands with high binding site concentrations. AB - The in situ formation and subsequent Cu(ii) ligation of the polydentate pro ligands o-[(E)-(2-hydroxy-3-methoxyphenyl)methylideneamino]benzohydroxamic acid (L1H3), o-[(E)-(2-hydroxy-3-methoxy-5 bromophenyl)methylideneamino]benzohydroxamic acid (L2H3) and o-[(E)-(2 hydroxyphenyl)methylideneamino]benzohydroxamic acid (L3H3), leads to the self assembly of the cages [Cu(ii)10(L1)4(2-aph)2(H2O)2](ClO4)4.5MeOH (), [Cu(ii)14(L1)8(MeOH)2.5(H2O)7.5](NO3)4.3MeOH.7H2O (), [Cu(ii)14(L2)8(MeOH)4(H2O)6](NO3)4.6H2O (), [Cu(ii)14(L3)8(MeOH)6(H2O)2](NO3)4.4MeOH.8H2O () and [Cu(ii)30O(OH)4(OMe)2(L1)16(MeOH)4(H2O)2](ClO4)4.2MeOH.30H2O (). Each member comprises a highly unusual topology derived from off-set, stacked, near planar layers of polynuclear subunits connected through long Cu(ii)-O contacts. The exact topology observed is dependent on the specific reaction conditions and methodologies employed. Dc magnetic susceptibility studies on , , and reveals strong antiferromagnetic exchange between the Cu(ii) centres in all siblings. We also present the 1D coordination polymer {[Cu(ii)(L4)].H2O}n () comprising the pseudo macrocyclic ligand [[2-[(E)-(2-hydroxy-3-methoxy phenyl)methyleneamino]benzoyl]amino]ethanimidate (L4H2), which is formed upon the incorporation of an MeCN unit at the hydroxamate group of precursor ligand L1H3. PMID- 26133040 TI - Self-reported versus measured body height and weight in Polish adult men: the risk of underestimating obesity rates. AB - BACKGROUND: In some epidemiological studies, self-reported height and weight are often used to save time and money. Self-reported height and weight are commonly used to assess the prevalence of obesity. The aim of this study was to assess the differences between self-reported and measured height and weight in adult men, and to determine how the accuracy of self-reported data depended on age and education. The prevalence of obesity was also calculated based both on self reported and measured data. MATERIAL AND METHODS: Data were collected during two population studies carried out in Wroclaw in 2010. One study included 1,194 19 year-old males who reported for the health examination mandated by the National Conscription Board (younger group). The other group included 355 men between 35 and 80 years old who reported for a ten-year follow-up (older group). Data were analyzed separately for both age groups. RESULTS: Both younger and older subjects overestimated their height by 1.4 cm and 1.0 cm (1.4 cm, 95 % CI: 1.26, 1.51, and 1.0 cm, 95 % CI: 0.85, 1.26, respectively). On average, younger subjects overestimated their weight by 0.7 kilograms (95 % CI: 0.55, 0.92), whereas older subjects underestimated their weight by 0.9 kilograms (95 % CI: -1.15, -0.48). The lower the level of education, the more the subjects overestimated their height. CONCLUSIONS: Adult men systematically overestimate their height and underestimate their weight. The magnitude of the inaccuracy depends on level of education. When self-reported data are used, the prevalence of obesity is generally underestimated. Using self-reported data to calculate BMI can lead to a substantial underestimation of the proportion of underweight and obese individuals in a population. Finally, using self-reported values for height in studies on social inequality may lead to false conclusions. : Background: In some epidemiological studies, self-reported height and weight are often used to save time and money. Self-reported height and weight are commonly used to assess the prevalence of obesity. The aim of this study was to assess the differences between self-reported and measured height and weight in adult men, and to determine how the accuracy of self-reported data depended on age and education. The prevalence of obesity was also calculated based both on self-reported and measured data. Material and methods: Data were collected during two population studies carried out in Wroclaw in 2010. One study included 1,194 19-year-old males who reported for the health examination mandated by the National Conscription Board (younger group). The other group included 355 men between 35 and 80 years old who reported for a ten-year follow-up (older group). Data were analyzed separately for both age groups. Results: Both younger and older subjects overestimated their height by 1.4 cm and 1.0 cm (1.4 cm, 95 %CI: 1.26, 1.51, and 1.0 cm, 95 %CI: 0.85, 1.26, respectively). On average, younger subjects overestimated their weight by 0.7 kilograms (95 %CI: 0.55, 0.92), whereas older subjects underestimated their weight by 0.9 kilograms (95 %CI: -1.15, -0.48). The lower the level of education, the more the subjects overestimated their height. Conclusions: Adult men systematically overestimate their height and underestimate their weight. The magnitude of the inaccuracy depends on level of education. When self-reported data are used, the prevalence of obesity is generally underestimated. Using self-reported data to calculate BMI can lead to a substantial underestimation of the proportion of underweight and obese individuals in a population. Finally, using self-reported values for height in studies on social inequality may lead to false conclusions. PMID- 26133041 TI - A Hard Nut to Crack: Reducing Chemical Migration in Food-Contact Materials. PMID- 26133043 TI - The global transcriptional landscape of Bacillus amyloliquefaciens XH7 and high throughput screening of strong promoters based on RNA-seq data. AB - Bacillus amyloliquefaciens is an important industrial microbe for the production of many industrial enzymes and primary metabolites. Although the complete genome sequence of B. amyloliquefaciens has been now published, transcript structures of B. amyloliquefaciens remain poorly defined. In this study, high-throughput RNA sequencing (RNA-seq) technology was applied to dissect the transcriptome of B. amyloliquefaciens strain XH7. In total, 3936 out of a total of 4204 B. amyloliquefaciens genes (93.6%) were transcribed under the selected growth condition. Transcriptional start sites (TSS) of 1064 annotated genes and 749 operons were identified. To screen for strong promoters, a beta-galactoside reporter was fused to eight candidate promoters from 288 genes with higher expression levels (RPKM values) than the control gene P43-bgaB. The results illustrated that the candidate promoter Pr2 (promoter for the sigW gene) displayed the strongest beta-galactosidase specific activity during the post-log phase, suggesting that it could be used effectively for heterologous gene expression. The presented data will contribute to the further study of the B. amyloliquefaciens transcriptome by identifying useful promoters for industrial uses. PMID- 26133044 TI - A Focus on Vaccine Development. PMID- 26133042 TI - H-ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses. AB - Aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H-Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H ficolin in fungal defence. Additionally, we investigated the presence of H ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H-Ficolin exhibited demonstrable binding to A. fumigatus conidia via l fucose, d-mannose and N-acetylglucosamine residues in a calcium- and pH-dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H-ficolin opsonization manifested an increase in interleukin-8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen activated protein kinase MAPK kinase 1/2, p38 MAPK and c-Jun N-terminal kinase. Finally, H-ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0.00726). Receiver operating characteristics curve analysis further highlighted the potential of H-ficolin as a diagnostic marker for lung infection (area under the curve = 0.77; P < 0.0001). Hence, H-ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus-host interactions and modulated immune responses. PMID- 26133045 TI - Immunization with Recombinant Adenoviral Vectors Expressing HCV Core or F Proteins Leads to T Cells with Reduced Effector Molecules Granzyme B and IFN gamma: A Potential New Strategy for Immune Evasion in HCV Infection. AB - Multispecific, broad, and potent T cell responses have been correlated with viral clearance in hepatitis C virus (HCV) infection. However, the majority of infected patients develop chronic infection, suggesting that natural infection mostly leads to development of inefficient T cell immunity. Multiple mechanisms of immune modulation and evasion have been shown in HCV infection through various investigations. This study examined the generation and modulation of T cell responses against core and frameshift (F) proteins of HCV. A single immunization of mice with replication incompetent recombinant adenovirus vectors encoding for F or core antigens induces poor T cell responses and leads to generation of CD4+ and CD8+ T cells with low granzyme B (GrB) expression. These T cells have impaired GrB enzyme activity and are unable to kill peptide loaded target cells. The low intracellular expression of GrB is not due to degranulation of cytotoxic granules containing cytotoxic T cells. Addition of exogenous IL-2 in in vitro cultures leads to partial recovery of GrB production, whereas immunization with the Toll-like receptor (TLR) agonist poly I:C leads to complete restoration of GrB expression in both CD4+ and CD8+ T cells. Thus, a possible new strategy of T cell modulation is recognized wherein effector T cells are caused to be dysfunctional by HCV-derived antigens F or core, and strategies are also delineated to overcome this dysfunction. These studies are important in the investigation of prophylactic vaccine and immunotherapy strategies for HCV infection. PMID- 26133046 TI - Role of Dendritic Cell-Specific ICAM-3-Grabbing Nonintegrin on Dendritic Cells in the Recognition of Hepatitis B Virus. AB - Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is an essential process for virus infection, such as HIV and hepatitis C, and plays a role in immune escape. However, the role of DC-SIGN in hepatitis B virus (HBV) infection is still unknown. The aim of this study was to investigate the role of DC-SIGN in mediating the maturation and activation of dendritic cells (DCs) when infected by HBV. Highly mannosylated HBV particles were obtained by treating HBV-producing HepG2.2.15 cells with the a-mannosidase I-inhibitor kifunensine. Highly mannosylated HBV or wild type HBV was added to infect the DCs of the DC-SIGN gene silencing group and normal group, respectively. Then, the expression of CDla, CD80, CD83, CD86 and HLA-DR on DCs was detected by flow cytometry, the capacity of stimulating lymphocyte proliferation was tested by MTT assay, the level of IL 12p70 that was released by DCs was measured by enzyme-linked immunosorbent assay, and the expression of the proteins NF-kappaBp65 and p38 was detected by western blot. Both wild type and highly mannosylated HBV could promote DCs maturation and activation. However, the highly mannosylated HBV could promote DCs immune activation more strongly. The difference in the effect on DCs between the two types of HBV could be eliminated by DC-SIGN gene silencing. DC-SIGN can promote the maturation and activation of DCs when recognized HBV, but wild type HBV can escape recognition by DC-SIGN to a certain extent with the help of demannosylated modification, leading to defective DCs function and chronic HBV infection. PMID- 26133047 TI - Use of Adjuvants to Enhance the Immune Response Induced by a DNA Vaccine Against Bovine Herpesvirus-1. AB - This study investigated the induction of humoral and cellular immune response by a DNA vaccine based on the bovine herpesvirus-1 (BoHV-1) glycoprotein D with commercial adjuvants (SEPPIC), in the murine model and in a preliminary assay in cattle, in order to select vaccines candidates that can improve cellular response. A DNA vaccine with most of the adjuvants used in this study was able to elicit a gD and viral-specific humoral immune response in vaccinated mice. Nevertheless, only a DNA vaccine with Montanide GEL 01 PR and Montanide Essai 903110 induced viral-specific proliferation and the highest levels of IFN-gamma secretion. Since a cellular response is important to deal with BoHV-1 infection, both adjuvants were tested in a small trial using bovines to corroborate improvement of a cellular response in the natural host. It was observed that a DNA vaccine with Montanide Essai 903110 induced the highest BoHV-1 specific IFN gamma production in cattle. So, this adjuvant is proposed as a suitable candidate to be tested in a BoHV-1 DNA vaccine for protection against viral challenge in bovines. PMID- 26133049 TI - Vaccine Technology V: The art of taking vaccines to disease prevention. PMID- 26133048 TI - Children with breakthrough varicella infection requiring hospitalization in Turkey (VARICOMP Study 2008-2013). AB - INTRODUCTION: Varicella in previously immunized individuals, known as "breakthrough varicella". While the majority of breakthrough cases are mild, some may be severe, requiring hospitalization in previously healthy children or children with an underlying condition. METHODS: This report, as a part of the prospective national pediatric varicella hospitalizations study (including 29 centers, represent 50% of pediatric population) in Turkey, is aimed to evaluate breakthrough varicella infection requiring hospitalization before the routine use of single-dose live varicella vaccine in national program from 2008 to 2013 (<10% of the pediatric age group received a single-dose vaccine). RESULTS: In the time period, 1939 children were hospitalized due to varicella infection in Turkey; 36 children (20 boys, 16 girls, mean age 68.0+37.6 months, all received single dose live varicella vaccine) with breakthrough varicella infection. Breakthrough varicella infection might be severe in previously healthy children (61.1%) and children with immune-compromising conditions (38.9%). The time elapsed between vaccination and hospitalization was approximately 5 years, and neurological complications, mainly encephalitis and meningitis, were the most common reason for hospitalization in previously healthy children. CONCLUSION: Pediatric breakthrough varicella requiring hospitalization have been seen in Turkey, is mainly observed in previously healthy children at 5 years after a single-dose varicella vaccine. The varicella vaccine has been implemented as part of the National Immunization Program in Turkey in 2013 (a single dose at age 12 months). Further surveillance in the same settings could evaluate the effectiveness of national immunization with single-dose varicella vaccine at 12 months of age and potential need for second dose of vaccine. PMID- 26133051 TI - Pneumothorax following nerve stimulator-guided axillary brachial plexus block in a dog. PMID- 26133050 TI - Detection of Small Pulmonary Nodules with Ultrashort Echo Time Sequences in Oncology Patients by Using a PET/MR System. AB - PURPOSE: To investigate the utility of a free-breathing ultrashort echo time (UTE) sequence for the evaluation of small pulmonary nodules in oncology patients by using a hybrid positron emission tomography (PET)/magnetic resonance (MR) imaging system and to compare the nodule detection rate between UTE and a conventional three-dimensional gradient-recalled-echo (GRE) technique. MATERIALS AND METHODS: In this HIPAA-compliant, institutional review board-approved prospective study, 82 pulmonary nodules were identified in eight patients with extrathoracic malignancies. Patients underwent free-breathing UTE and dual-echo three-dimensional GRE imaging of the lungs in a hybrid PET/MR imaging unit immediately after clinical PET/computed tomography (CT). CT was considered the reference standard for nodule detection. Two reviewers identified nodules and obtained measurements on MR images. The McNemar test was used to evaluate differences in nodule detection rate between MR techniques, and interrater agreement was assessed by using Bland-Altman plots. RESULTS: Mean nodule diameter +/- standard deviation was 6.2 mm +/- 2.7 (range, 3-17 mm). The detection rate was higher for UTE imaging than for dual-echo GRE imaging for nodules of at least 4 mm (82% vs 34%, respectively; P < .001), with the largest difference in detection noted in the 4-8-mm nodule group (79% vs 21%, P < .001). UTE imaging displayed a higher detection rate than dual-echo GRE imaging for nodules without fluorodeoxyglucose avidity (68% vs 22%, respectively; P < .001). Interrater reliability of nodule detection with MR imaging was high (kappa = 0.90 for UTE imaging and kappa = 0.92 for dual-echo GRE imaging). CONCLUSION: A free-breathing UTE sequence has high sensitivity for the detection of small pulmonary nodules (4 8 mm) and outperformed a three-dimensional dual-echo GRE technique for the detection of small, non-fluorodeoxyglucose-avid nodules. PMID- 26133052 TI - Dynamics of Single Hydrogen Bubbles at a Platinum Microelectrode. AB - Bubble dynamics, including the formation, growth, and detachment, of single H2 bubbles was studied at a platinum microelectrode during the electrolysis of 1 M H2SO4 electrolyte. The bubbles were visualized through a microscope by a high speed camera. Electrochemical measurements were conducted in parallel to measure the transient current. The periodic current oscillations, resulting from the periodic formation and detachment of single bubbles, allow the bubble lifetime and size to be predicted from the transient current. A comparison of the bubble volume calculated from the current and from the recorded bubble image shows a gas evolution efficiency increasing continuously with the growth of the bubble until it reaches 100%. Two different substrates, glass and epoxy, were used to embed the Pt wire. While nearly no difference was found with respect to the growth law for the bubble radius, the contact angle differs strongly for the two types of cell. Data provided for the contact point evolution further complete the image of single hydrogen bubble growth. Finally, the velocity field driven by the detached bubble was measured by means of PIV, and the effects of the convection on the subsequent bubble were evaluated. PMID- 26133053 TI - An Auto-Ethnographic Study of "Open Dialogue": The Illumination of Snow. AB - This auto-ethnographic study describes the changes in the author's thinking and clinical work connected to her first-hand experience of Open Dialogue, which is an innovative, psychosocial approach to severe psychiatric crises developed in Tornio, Finland. In charting this trajectory, there is an emphasis on three interrelated themes: the micropolitics of U.S. managed mental health care; the practice of "dialogicality" in Open Dialogue; and the historical, cultural, and scientific shifts that are encouraging the adaptation of Open Dialogue in the United States. The work of Gregory Bateson provides a conceptual framework that makes sense of the author's experience and the larger trends. The study portrays and underscores how family and network practices are essential to responding to psychiatric crises and should not be abandoned in favor of a reductionist, biomedical model. PMID- 26133054 TI - Unilateral adrenal hemorrhagic infarction in essential thrombocythemia. AB - Adrenal hemorrhage is a rare disease associated with various conditions. We report a case of a 68-year-old woman with abdominal and back pain. The diagnostic work-up showed a left adrenal gland infarction associated with essential thrombocythemia. Treatment consisted in painkillers and treating the underlying condition in order to prevent further thrombotic events. PMID- 26133055 TI - Evaluation of the Effect of N-Acetylcysteine on Protein Deposition on Contact Lenses in Patients with the Boston Keratoprosthesis Type I. AB - PURPOSE: To establish the efficacy of topical N-acetylcysteine (NAC) as a treatment to reduce protein deposition on the contact lens surface. METHODS: In this prospective, nonrandomized clinical trial, a total of 10 eyes (9 patients) were enrolled from a single center. All patients had a prior ocular history of either a Boston Keratoprosthesis type I or trichiasis from Stevens-Johnson syndrome, which necessitated full-time contact lens wear. Four visits were required to complete the study. During visit 1, a new contact lens was inserted and a baseline examination was performed. Visit 2 served as the control month, whereas visits 3 and 4 were month 1 and 2 on treatment with 20% NAC. At the end of each visit the contact lens was replaced. The lenses from visit 2 (control month-without NAC) and from visit 3 (treatment month-with NAC) were collected for proteomic analysis. The main outcome measures were to quantify protein deposition, as well as to assess the visual acuity and ocular surface symptoms before and after treatment. RESULTS: Topical NAC resulted in a 20% decrease in protein deposition. This correlated with a trend for improvement in visual acuity and increased subjective improvement in vision at month 1 (P=0.0153) and 2 (P=0.0016). CONCLUSIONS: NAC reduced protein deposition, decreased ocular surface symptoms, and improved contact lens transparency, thereby providing increased optical clarity. PMID- 26133056 TI - Effect of Glaucoma Medication in Tear Film Osmolarity of Patients Without Symptoms of Ocular Discomfort. AB - PURPOSE: To evaluate tear film osmolarity in patients with no symptoms of ocular discomfort treated with intraocular pressure (IOP)-lowering medication and compare it with tear film osmolarity of controls. METHODS: This was a cross sectional study of 61 patients with glaucoma or ocular hypertension (study group) and 32 age-matched normals (control group). Neither group of patients reported ocular discomfort. Tear film osmolarity was measured with the TearLab Osmolarity System (TearLab Corp, San Diego, CA), and results were compared between groups. Correlation of osmolarity with parameters associated with medication use (time, number of medications, and number of instillations) was assessed. RESULTS: Mean age of the patients in the medication group was 71+/-10.18 years and in the control group was 69+/-10.23 years (P=0.247). In the medication group, the tear film osmolarity was 295.56+/-12.54 mOsms/L and in the control group, it was 294.84+/-14.73 mOsms/L (P=0.807). Regarding the percentage of patients with tear film hyperosmolarity (osmolarity>=316 mOsms/L), in the group of normal patients, 3 had osmolarity more than or equal to the selected cutoff value (9.3%) and in the medication group, 7 patients (8.2%). Difference of the percentage between groups was not statistically significant (P=0.999, chi-square test). Tear film osmolarity in the medication group was not correlated to any of the parameters related to treatment. CONCLUSIONS: Patients treated with IOP-lowering medication do not exhibit tear film hyperosmolarity as long as they do not report symptoms of ocular discomfort. PMID- 26133057 TI - Efficacy and Safety of Glaucoma Patients' Switch from a 2% Dorzolamide/0.5% Timolol Fixed-Combination Brand-Name Drug to Its Generic Counterpart. AB - PURPOSE: To compare the efficacy and safety of the brand-name and generic 2% dorzolamide/0.5% timolol fixed-combination (DTFC) drugs in glaucoma patients. METHODS: This was a prospective single-center study, in which patients using only the brand-name DTFC (Cosopt((r)); Merck and Co, Inc.) drug and those using Cosopt with prostaglandin analogs (PGs) were enrolled. In the patients using Cosopt (Group A) and Cosopt with PGs (Group B), Cosopt was switched to its generic counterpart (Batidor((r)); Bausch & Lomb, Inc.). The intraocular pressure (IOP) was measured before the switch and 4, 8, and 12 weeks after the switch in both groups. The questionnaire on the discomfort symptoms and on the discomfort score for the use of eye drops was answered by the patients in both groups before the switch and 12 weeks after the switch. RESULTS: A total of 112 patients were enrolled in the study, 62 in Group A and 50 in Group B. The IOPs before the switch and 4, 8, and 12 weeks after the switch showed no statistical difference in both groups (P>0.05). There were higher incidences of bitter taste and blurring with Cosopt, and there was a higher incidence of headache with Batidor in both groups, but no significant differences (P>0.05) were noted. There was, likewise, no significant difference in the discomfort score between 2 drugs in both groups (P>0.05). CONCLUSIONS: After the switch, the IOP-lowering effect of the generic drug Batidor was similar to that of the brand-name drug Cosopt in the monotherapy and combination therapy with PGs. No significant differences were found in terms of the discomfort symptoms and discomfort score between the 2 drugs. PMID- 26133058 TI - The Efficiency of Intravitreal Dexamethasone Implants in the Treatment of Macular Edema Secondary to Retinal Vein Occlusion. AB - PURPOSE: To evaluate the efficacy and safety of dexamethasone (DEX) intravitreal implant for the treatment of macular edema due to branch retinal vein occlusion. METHODS: We included 22 eyes of 22 patients in this retrospective study. Visual acuity tested in logMAR with Early Treatment Diabetic Retinopathy Study (ETDRS) chart, central macular thickness (CMT) measurements, intraocular pressure (IOP), and side effects after treatment were observed monthly. RESULTS: Best corrected visual acuity improved significantly in the first 3 months after the first intravitreal DEX implantation, but no statistically significant change was observed in the following 3 months. Statistically significant improvement was observed in the first 4 months after the second injection of DEX implant, but no statistically significant change was observed in the 2 following months. A statistically significant decrease in CMT was observed in the first 4 months after the first injection, but no statistically significant change was observed in the following 2 months. A statistically significant decrease in CMT was observed in the first 3 months after the second injection, but no statistically significant change was observed in the following 3 months. The IOP could be controlled with medication in all the participants with elevated IOP. Of the patients, 3 had cataracts requiring surgery. CONCLUSION: Both functional and anatomical effects of DEX implant were obvious in the first 3 months after injection. Repeated injections and frequent examination might be required. Side effects such as cataract may require surgical intervention, whereas IOP elevation may be managed by topical drops. PMID- 26133059 TI - Choroidal Thickness Changes After Intravitreal Antivascular Endothelial Growth Factor Therapy for Age-Related Macular Degeneration: Ranibizumab Versus Aflibercept. AB - PURPOSE: To compare the changes in subfoveal choroidal thickness (CT) in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal ranibizumab or aflibercept. METHODS: In this retrospective case series, the medical records of 28 patients with nAMD treated with at least 3 consecutive monthly injections of ranibizumab (0.5 mg/0.05 mL) or aflibercept (2 mg/0.05 mL) between December 2013 and June 2014 and who were followed up for at least 3 months were reviewed. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography. RESULTS: Choroidal thickness decreased over time in the aflibercept group, but was unchanged throughout the study in the ranibizumab group. At each time point, the decrease was significantly greater in aflibercept-treated eyes compared with ranibizumab treated eyes (P<0.05). No significant change in best-corrected visual acuity (BCVA) was seen in either group during follow-up. There was no correlation between change in choroidal thickness and age, sex, duration of previous antivascular endothelial growth factor treatment, number of previous injections, spherical equivalent, baseline choroidal thickness, and the BCVA outcome in either group. CONCLUSIONS: Subfoveal choroidal thickness appeared to decrease significantly in eyes with nAMD during 3 months of aflibercept treatment. No corresponding decrease in choroidal thickness occurred in ranibizumab-treated eyes. PMID- 26133060 TI - Suppression of heme oxygenase-1 activity reduces airway hyperresponsiveness and inflammation in a mouse model of asthma. AB - OBJECTIVE: Carbon monoxide (CO) levels in expired gas are higher in patients with bronchial asthma than in healthy individuals. Heme oxygenase-1 (HO-1) is a rate limiting enzyme that catalyzes the degradation of heme to yield biliverdin, CO and free iron. Thus, HO-1 is implicated in the pathogenesis of bronchial asthma. However, whether HO-1 expression and activity in lung tissue are related to allergic airway inflammation remains unclear. We investigated whether expression of HO-1 is related to allergic airway inflammation in lungs and whether HO-1 could influence airway hyperresponsiveness and eosinophilia in mice sensitized to ovalbumin (OVA). METHODS: C57BL/6 mice immunized with OVA were challenged thrice with an aerosol of OVA every second day for 8 days. HO-1-positive cells were identified by immunostaining in lung tissue, and zinc protoporphyrin (Zn-PP), a competitive inhibitor of HO-1, was administered intraperitoneally to OVA immunized C57BL/6 mice on day 23 (day before inhalation of OVA) and immediately before inhalation on the subsequent 4 days (total five doses). Mice were analyzed for effects of HO-1 on AHR, inflammatory cell infiltration and cytokine levels in lung tissue. Ethical approval was obtained from the concerned institutional review board. RESULTS: Number of HO-1-positive cells increased in the subepithelium of the bronchi after OVA challenge, and HO-1 localized to alveolar macrophages. Zn-PP clearly inhibited AHR, pulmonary eosinophilia and IL-5 and IL 13 expression in the lung tissue. CONCLUSION: Expression of HO-1 is induced in lung tissue during attacks of allergic bronchial asthma, and its activity likely amplifies and prolongs allergic airway inflammation. PMID- 26133061 TI - Ethnopharmacological analysis of medicinal plants used against non-communicable diseases in Rodrigues Island, Indian Ocean. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Rodrigues is an autonomous outer island that form part of the Republic of Mauritius and one of three islands that constitute the Mascarene archipelago in the Indian Ocean. Though herbal medicine is in common use in Rodrigues, there has been no ethnopharmacological study to document quantitatively such traditional practise particularly against non-communicable diseases (NCD) which is currently a growing major health issue on the island. The aim of the present study was to collect, analyse and document traditionally used medicinal plants (MP) from key informants and traditional medicine practitioners (TMP) in the tropical island of Rodrigues to treat and/or manage common NCD. MATERIALS AND METHODS: Data was collected via face-to-face interviews with MP users (n=113) and TMP (n=9). Seven quantitative ethnopharmacological indices, namely family use value (FUV), use value (UV), informant agreement ratio (IAR), relative frequency of citation (RFC), fidelity level (FL), relative importance (RI) and ethnobotanicity index (EI) were calculated. RESULTS: Hundred and three plants belonging to 55 families were recorded for the treatment and/or management of 27 different NCD. Three of the MP (Terminalia bentzoe (L.) L.F, Sarcostemma cf. adontolepis Balf.f. and Clerodendrum laciniatum Balf.f.) recorded are endemic to Rodrigues and 2 (Carissa xylopicron Thouars., Phyllanthus casticum Willemet f.) endemic to the Mascarene Islands. The most solicited MP family was Asteraceae with a total of 8 species. Citrus aurantifolia (Christm.) Swingle scored the highest RFC (RFC=1.02) value. Ten plants were found to score 100% FL and the highest IAR (0.98) was observed for the disease category of certain conditions originating in the perinatal period. Arecaceae scored the highest FUV value and Ayapana triplinervis (Vahl) R.M. King et H.Rob highest UV (UV= 2.72). CONCLUSION: Given the dearth of updated information on traditional medicine of Rodrigues, this study can provide an opportunity to establish valuable primary information on the different MP used by the local people and hence can open new perspectives for further pharmacological research. PMID- 26133062 TI - Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic against alpha-naphthylisothiocyanate-induced cholestatic liver injury in rats. AB - ETHNOPHARMACOLOGY RELEVANCE: The decoction of the flowers of Abelmoschus manihot (L.) Medic was traditionally used for the treatment of jaundice and various types of chronic and acute hepatitis in Anhui and Jiangsu Provinces of China for hundreds of years. Phytochemical studies have indicated that total flavonoids extracted from flowers of A. manihot (L.) Medic (TFA) were the major constituents of the flowers. Our previous studies have investigated the hepatoprotective effects of the TFA against carbon tetrachloride (CCl4) induced hepatocyte damage in vitro and liver injury in vivo. This study aimed to investigate the protective effects and mechanisms of TFA on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in rats. MATERIAL AND METHODS: The hepatoprotective activities of TFA (125, 250 and 500mg/kg) were investigated on ANIT-induced cholestatic liver injury in rats. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were used as indices of hepatic cell damage and measured. Meanwhile, the serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA) were used as indices of biliary cell damage and cholestasis and evaluated. Hepatic malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione transferase (GST), tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) were measured in the liver homogenates. The bile flow in 4h was estimated and the histopathology of the liver tissue was evaluated. Furthermore, the expression of transporters, bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and Na(+)-taurocholate cotransporting polypeptide (NTCP) were studied by western blot and reverse transcription-quantitative real-time polymerase chain reaction (RT-PCR) to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. RESULTS: The oral administration of TFA to ANIT treated rats could reduce the increases in serum levels of ALT, AST, LDH, ALP, GGT, TBIL, DBIL and TBA. Decreased bile flow by ANIT was restored with TFA treatment. Concurrent administration of TFA reduced the severity of polymorphonuclear neutrophil infiltration and other histological damages, which were consistent with the serological tests. Hepatic MDA and GSH contents in liver tissue were reduced, while SOD and GST activities, which had been suppressed by ANIT, were elevated in the groups pretreated with TFA. With TFA intervention, levels of TNF-alpha and NO in liver were decreased. Additionally, TFA was found to increase the expression of liver BSEP, MRP2, and NTCP in both protein and mRNA levels in ANIT-induced liver injury with cholestasis. CONCLUSION: TFA exerted protective effects against ANIT-induced liver injury. The possible mechanisms could be related to anti-oxidative damage, anti-inflammation and regulating the expression of hepatic transporters. It layed the foundation for the further research on the mechanisms of cholestasis as well as the therapeutic effects of A. manihot (L.) Medic for the treatment of jaundice. PMID- 26133063 TI - "The medicine from behind": The frequent use of enemas in western African traditional medicine. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Purgative enemas form an integral part of African traditional medicine. Besides possible benefits, serious health risks of rectal herbal therapy have been described in literature. To design appropriate health education programs, it is essential to understand traditional herbal practices and local perceptions of health and illness. Little is known about the herbal ingredients of enemas in Sub-Saharan Africa and consumers' personal reasons to use them. AIM OF THE STUDY: To analyze the importance of enema use with regard to plant species used and illnesses treated in West and Central Africa, to understand the local health beliefs that underlie frequent enema use and to evaluate which recipes and practices could be beneficial or harmful. MATERIALS AND METHODS: We extracted data from 266 ethnobotanical questionnaires on medicinal (in particular women's health and childcare) and ritual plant use in Ghana, Benin and Gabon. Plants mentioned during interviews were vouchered and identified in herbaria. Health issues treated by means of enemas were ranked according to the number of plant species used for a specific illness. We compared our results with findings of medical research on benefits and risks of enema use in Sub-Saharan Africa. RESULTS: We recorded ca. 213 different plant species used in hundreds of recipes for rectal insertions, mostly in Ghana and Gabon. Stomachache, abdominal pain, female infertility and birth facilitation were treated with the highest number of plants species. Cleansing the intestines of young children to promote their health by getting rid of 'dirt', instead of treating constipation, was an important cultural practice that required the rectal application of herbal medicine, as well as other cultural bound health issues like stimulating children to walk at an early age. Tradition, the bitter taste of herbal medicine and the rapid effect of enemas were frequently mentioned reasons for enema use. DISCUSSION AND CONCLUSIONS: Literature indicates that although enemas can help to improve the hygienic conditions of a household with young infants, frequent enema use can pose serious risks like direct toxicity caused by harmful ingredients, mechanical injury and infections. In Africa, enemas containing herbal medicine are common methods of administering herbal medicine for a variety of diseases, rather than just medicinal treatments for constipation as previously thought. Health professionals should be aware of the extent of, and motivation behind enema use to develop culturally appropriate education programs, especially targeted at vulnerable groups such as elderly people, parents of young infants and pregnant women. PMID- 26133064 TI - Unusual O-alkylation of 2-hydroxy-1,4-naphthoquinone utilizing alkoxymethyl chlorides. AB - A new type of O-alkylation of 2-hydroxy-1,4-naphthoquinone with alkoxymethyl chlorides is described. The reaction course can be controlled by the choice of base and yields O-alkylated or O-alkoxymethylated products in high yield with high selectivity. PMID- 26133065 TI - Novel pH-responsive polymeric micelles prepared through self-assembly of amphiphilic block copolymer with poly-4-vinylpyridine block synthesized by mechanochemical solid-state polymerization. AB - We fabricated polymeric micelles containing 5-fluorouracil (5-FU) or fluorescein using the amphiphilic block copolymer, poly-4-vinylpyridine-b-6-O-methacryloyl galactopyranose. Although the polymeric micelles were stable at pH 7.4, they readily decomposed at pH 5, resulting in near complete release of 5-FU. Uptake of polymeric micelles containing fluorescein by HepG2 and HCT116 cells was also investigated. With both cell types, strong fluorescence was observed after a 12-h incubation, but the fluorescence weakened after 24 h of incubation. The fluorescein incorporated into the polymeric micelles was released into acidic organelles (endosome and/or lysosome), from which it diffused throughout the cell. The cytotoxicity of polymeric micelles containing 5-FU was evaluated against HepG2 cells using a CCK-8 assay. The results suggest that polymeric micelles containing 5-FU are more cytotoxic to HepG2 cells than free 5-FU. PMID- 26133066 TI - Synthesis and anticancer activity of some new thiopyrano[2,3-d]thiazoles incorporating pyrazole moiety. AB - The knoevenagel condensation of 3-phenyl-4-thioxo-2-thiazolidinone (1) with 1 phenyl-3-aryl-1H-pyrazole-4-carbaldehydes 2a-d in refluxing glacial acetic acid or in polyethylene glycol-400 (PEG-400) at room temperature without catalyst, afforded the corresponding 5-hetarylmethylene derivatives 3a-d. [4+2]Cycloaddition reaction of compounds 3 with N-arylmaleimides, acrylonitrile and ethyl acrylate afforded thiopyrano[2,3-d]thiazole derivatives 5a-p. The anticancer activity of some of the newly synthesized compounds was investigated against different human cancer cell lines (MCF7 and HEPG2) and confirmed by molecular docking. Moreover, the structure for one representative example of the new products was confirmed by X-ray crystallography. The structure of all the newly synthesized compounds was established by elemental and spectral data. PMID- 26133068 TI - Synthetic approaches for sulfur derivatives containing 1,2,4-triazine moiety: their activity for in vitro screening towards two human cancer cell lines. AB - A series of sulfur 1,2,4-triazine derivatives were prepared and evaluated as anticancer compounds for two human breast cancer cell lines (MCF-7, MDA-MB-231) with some of them acting as low micromolar inhibitors. Evaluation of the cytotoxicity using a 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium bromide (MTT) assay, the inhibition of [(3)H]thymidine incorporation into DNA, and collagen synthesis inhibition demonstrated that these products exhibit cytotoxic effects on these breast cancer cell lines in vitro. The most effective were disulfide and sulfenamide compounds with two valence sulfur atoms. A structure activity relationship study was performed using X-ray analysis and theoretical calculations at an ab initio density functional theory (DFT) level. PMID- 26133067 TI - P-Glycoprotein (ABCB1) limits the brain distribution of YQA-14, a novel dopamine D3 receptor antagonist. AB - YQA-14 is a promising agent for treating addiction to cocaine and opioids. However, previous studies have showed there is marked contrast between the relatively small differences in pharmacological action in vivo and the large differences in their respective receptor binding properties in vitro. We hypothesized that the conflict between the in vivo and in vitro outcomes was attributable to poor brain exposure to YQA-14 caused by drug efflux transporters. To address this issue, we investigated the directional flux of YQA-14 across Caco 2 cells at 37 degrees C or 4 degrees C and the bidirectional transport in the presence and absence of transporter chemical inhibitors. These phenomena were further investigated by an in vivo determination of the brain and blood pharmacokinetics (PK) profile of YQA-14 following intraperitoneal administration with and without inhibitor. The efflux ratio of YQA-14 on Caco-2 cell monolayers was 2.39 and the efflux was temperature-dependent. When co-incubated with GF120918 or LY335979, the efflux of YQA-14 was markedly decreased. However, there was no significant difference in the permeability of YQA-14 when the cells were treated with Ko143. In vivo experiments showed that the brain-to-plasma ratio increased by more than 75-fold and 20-fold with co-administration of GF120918 and LY335979, respectively. Use of Ko143 did not change the brain-to-blood ratio of YQA-14. The results indicate that the brain distribution of YQA-14 was restricted because of active efflux transport at the blood brain barrier. In addition, P glycoprotein (P-gp) played a dominant role in limiting the distribution of YQA-14 to the brain. PMID- 26133069 TI - A new methodology for functionalization at the 3-position of indoles by a combination of boron Lewis acid with nitriles. AB - We discovered that a reagent comprising a combination of PhBCl2 and nitriles was useful for syntheses of both 3-acylindoles and 1-(1H-indol-3-yl)alkylamine from indoles. The reaction proceeded selectively at the 3-position of indoles providing 3-acylindoles in moderate to high yields on treatment with the above reagent. Furthermore, the reaction provided the corresponding amine products in moderate to high yields after the intermediate imine was reduced by NaBH3CN. These reactions proceeded under mild conditions and are applicable to the formation of indoles functionalized at the 3-position. PMID- 26133070 TI - Sesquiterpenes from the fruiting bodies of Ramaria formosa and their human neutrophil elastase inhibitory activity. AB - Two new sesquiterpene derivatives (1 and 2), ramarin A (1) and ramarin B (2), together with three known compounds (3-5) were isolated from the fruiting bodies of Ramaria formosa. The structures of the two sesquiterpenes were established by extensive spectroscopic studies and chemical evidence. The inhibitory activity of the isolated compounds (1-5) against human neutrophil elastase (HNE) was evaluated in vitro. All compounds tested inhibited HNE by 35-30% at the highest concentration used (100 uM), whereas the positive control, epigallocatechin gallate (EGCG), exhibited 60% inhibition at 100 uM. PMID- 26133071 TI - Anti-inflammatory tirucallane saponins from Paramignya scandens. AB - Five new tirucallane saponins, paramignyosides A-E (1-5), were isolated from the water fraction of the Paramignya scandens stem and leaves. Their structures were elucidated on the basis of spectroscopic evidence including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one dimensional (1D)- and 2D-NMR. The effects of isolated compounds on pro-inflammatory cytokines were evaluated by measuring the production of interleukin (IL)-12 p40, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Paramignyoside C (3) exhibited selective and potent inhibitory effect (IC50=5.03+/-0.19 uM) on the production of IL-12 p40 comparable to that of the positive control, SB203580 (IC50=5.00+/-0.16 uM). Further studies are required to confirm efficacy in vivo and the mechanism of anti-inflammatory effects. PMID- 26133072 TI - Estrogen receptor 2b deficiency impairs the antiviral response of zebrafish. AB - Although several studies have demonstrated the ability of some endocrine disruptive chemicals (EDCs) to alter the physiology of zebrafish, the immune reproductive interaction has received little attention in this species. In this study, we used a homozygous line carrying an insertion of 8 amino acids in the ligand-binding domain of the estrogen receptor 2b gene (esr2b) to further understand the role of estrogen signaling on innate immunity. Adult mutant fish showed distorted sexual ratios related with alterations in testicular morphology and supraphysiological testosterone and 17beta-estradiol (E2) levels. Immunity wise, although esr2b mutant fish showed unaltered antibacterial responses, they were unable to mount an effective antiviral response upon viral challenge. RT qPCR analysis demonstrated that mutant fish were able to induce the genes encoding major antiviral molecules, including Ifnphi1, Ifnphi2, Infphi3, Mxb and Mxc, and the negative feedback regulator of cytokine signaling Socs1. Notably, although esr2b mutant larvae showed a similar resistance to SVCV infection to their wild type siblings, waterborne E2 increased their viral susceptibility. Similarly, the exposure of adult wild type zebrafish to E2 also resulted in increased susceptibility to SVCV infection. Finally, the administration of recombinant Ifnphi1 hardly reversed the higher viral susceptibility of esr2b mutant zebrafish, suggesting that elevated socs1 levels impair Ifn signaling. All together, these results uncover an important role for E2 and Esr signaling in the fine-tuning of sexual hormone balance and the antiviral response of vertebrates. PMID- 26133073 TI - Optimizing the flattening filter free beam selection in RapidArc(r)-based stereotactic body radiotherapy for Stage I lung cancer. AB - OBJECTIVE: To optimize the flattening filter-free (FFF) beam selection in stereotactic body radiotherapy (SBRT) treatment for Stage I lung cancer in different fraction schemes. METHODS: Treatment plans from 12 patients suffering from Stage I lung cancer were designed using the 6XFFF and 10XFFF beams in different fraction schemes of 4 * 12, 3 * 18 and 1 * 34 Gy. Plans were evaluated mainly in terms of organs at risk (OARs) sparing, normal tissue complication probability (NTCP) estimation and treatment efficiency. RESULTS: Compared with the 10XFFF beam, 6XFFF beam showed statistically significant lower dose to all the OARs investigated. The percentage of NTCP reduction for both lung and chest wall was about 10% in the fraction schemes of 4 * 12 and 3 * 18 Gy, whereas only 7.4% and 2.6% was obtained in the 1 * 34 Gy scheme. For oesophagus, heart and spinal cord, the reduction was greater with the 6XFFF beam, but their absolute estimates were <10(-6)%. The mean beam-on time for 6XFFF and 10XFFF beams at 4 * 12, 3 * 18 and 1 * 34 Gy schemes were 2.2 +/- 0.2 vs 1.5 +/- 0.1, 3.3 +/- 0.9 vs 2.0 +/- 0.5 and 6.3 +/- 0.9 vs 3.5 +/- 0.4 min, respectively. CONCLUSION: The 6XFFF beam obtains better OARs sparing and lower incidence of NTCP in SBRT treatment of Stage I lung cancer, whereas the 10XFFF beam improves the treatment efficiency. To balance the OARs sparing and intrafractional variation owing to the prolonged treatment time, the authors recommend using the 6XFFF beam in the 4 * 12 and 3 * 18 Gy schemes but the 10XFFF beam in the 1 * 34 Gy scheme. ADVANCES IN KNOWLEDGE: This study optimizes the FFF beam selection in different fraction schemes in SBRT treatment of Stage I lung cancer. PMID- 26133074 TI - Biliary dilatation in the presence of a periampullary duodenal diverticulum. AB - OBJECTIVE: Periampullary diverticulum (PAD) often presents as an incidental CT finding. Its significance and its effect on biliary dilation are unclear. The aim of our study was to determine if the presence of a PAD is associated with abnormal dilation of the common bile duct (CBD). METHODS: Patients with PAD were retrospectively identified from the radiology database from November 2011 to November 2012 and those with known pancreaticobiliary pathology were excluded, except patients with cholelithiasis and prior cholecystectomy. A total of 150 patients with PAD were selected as well as a control group of 150 patients with no PAD. Data with respect to demographics, PAD size and location, ductal diameter, previous cholecystectomy and liver function tests were collected. To compare the groups, the Student's t-test and chi(2) analysis were used where appropriate. RESULTS: The male : female ratio was 1 : 1.2 with a median average of 71 years in the PAD group. There was no statistical difference in the CBD measurement (at the pre-ampulla and pancreatic head, and distal to confluence) between the PAD and control groups (4.8, 6.9 and 6.8 mm for the PAD group; 4.7, 6.8 and 6.4 mm for the control group; p = 0.5, 0.7 and 0.3). Also, no difference was observed in the right and left intrahepatic biliary ducts (2.7, 2.7 mm for the PAD group; 2.5, 2.6 mm for the control group; p = 0.2, 0.6). There was a significantly higher incidence of cholecystectomy history (23% vs 8.7%, p < 0.01) and cholelithiasis (22% vs 11%, p < 0.01) in the PAD group, and no difference in the liver function tests. Subgroup analysis of small vs large PAD (<20 mm, >=20 mm) did not show a difference in the CBD and intrahepatic biliary duct measurements. When comparing cholecystectomy vs non-cholecystectomy groups, CBD measurements were significantly higher in the cholecystectomy group. CONCLUSION: Our study confirms that PAD on its own does not lead to abnormal CBD dilatation. However, increased incidence of cholelithiasis and cholecystectomy was noted in the presence of PAD. ADVANCES IN KNOWLEDGE: PAD on its own does not cause CBD dilatation. PMID- 26133076 TI - Straightforward Synthesis of Purine 4'-Alkoxy-2'-deoxynucleosides: First Report of Mixed Purine-Pyrimidine 4'-Alkoxyoligodeoxynucleotides as New RNA Mimics. AB - Purine and pyrimidine 4'-alkoxy-2'-deoxynucleosides were efficiently prepared from nucleoside 4'-5'-enol acetates in three steps by N-iodosuccinimide promoted alkoxylation, hydrolysis, and reduction followed by conversion to phosphoramidite monomers for the solid-phase synthesis of the oligonucleotides. Fully modified 4' alkoxyoligodeoxynucleotides, which are characterized by a prevalent N-type (RNA like) conformation, exhibited superior chemical and nuclease resistance as well as excellent hybridization properties with a strong tendency for RNA-selective hybridization, suggesting a potential application of 4'-alkoxy oligodeoxynucleotides in antisense technologies. PMID- 26133077 TI - Habituation to a stressor predicts adolescents' adiposity. AB - BACKGROUND AND OBJECTIVES: Stress is associated with gains in adiposity. One factor that determines how much stress is experienced is how quickly an adolescent reduces responding (habituates) across repeated stressors. The purpose of this study was to determine the association of body mass index (BMI) percentile and the rate of habituation to a stressor. DESIGN: Thirty-four adolescents completed anthropometric measures and a habituation protocol using a within study design. METHODS: The habituation protocol measured the rate of decline in perceived stress and heart rate (HR) across four, two-minute serial subtraction trials. RESULTS: Multivariate linear regression revealed the habituation rate of the HR predicted BMI percentile after adjusting for gender, socioeconomic status, and initial HR (beta = 17.2, p < .04). CONCLUSIONS: Slower habituation to a laboratory stressor was associated with greater BMI percentiles in adolescents. PMID- 26133075 TI - Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation. AB - Molecular imaging provides considerable insight into biological processes for greater understanding of health and disease. Numerous advances in medical physics, chemistry and biology have driven the growth of this field in the past two decades. With exquisite sensitivity, depth of detection and potential for theranostics, radioactive imaging approaches have played a major role in the emergence of molecular imaging. At the same time, developments in materials science, characterization and synthesis have led to explosive progress in the nanoparticle (NP) sciences. NPs are generally defined as particles with a diameter in the nanometre size range. Unique physical, chemical and biological properties arise at this scale, stimulating interest for applications as diverse as energy production and storage, chemical catalysis and electronics. In biomedicine, NPs have generated perhaps the greatest attention. These materials directly interface with life at the subcellular scale of nucleic acids, membranes and proteins. In this review, we will detail the advances made in combining radioactive imaging and NPs. First, we provide an overview of the NP platforms and their properties. This is followed by a look at methods for radiolabelling NPs with gamma-emitting radionuclides for use in single photon emission CT and planar scintigraphy. Next, utilization of positron-emitting radionuclides for positron emission tomography is considered. Finally, recent advances for multimodal nuclear imaging with NPs and efforts for clinical translation and ongoing trials are discussed. PMID- 26133078 TI - Deciphering the evolution of birdwing butterflies 150 years after Alfred Russel Wallace. AB - One hundred and fifty years after Alfred Wallace studied the geographical variation and species diversity of butterflies in the Indomalayan-Australasian Archipelago, the processes responsible for their biogeographical pattern remain equivocal. We analysed the macroevolutionary mechanisms accounting for the temporal and geographical diversification of the charismatic birdwing butterflies (Papilionidae), a major focus of Wallace's pioneering work. Bayesian phylogenetics and dating analyses of the birdwings were conducted using mitochondrial and nuclear genes. The combination of maximum likelihood analyses to estimate biogeographical history and diversification rates reveals that diversity-dependence processes drove the radiation of birdwings, and that speciation was often associated with founder-events colonizing new islands, especially in Wallacea. Palaeo-environment diversification models also suggest that high extinction rates occurred during periods of elevated sea level and global warming. We demonstrated a pattern of spatio-temporal habitat dynamics that continuously created or erased habitats suitable for birdwing biodiversity. Since birdwings were extinction-prone during the Miocene (warmer temperatures and elevated sea levels), the cooling period after the mid-Miocene climatic optimum fostered birdwing diversification due to the release of extinction. This also suggests that current global changes may represent a serious conservation threat to this flagship group. PMID- 26133080 TI - Optimizing the dermal accumulation of a tazarotene microemulsion using skin deposition modeling. AB - CONTEXT: It is well known that microemulsions are mainly utilized for their transdermal rather than their dermal drug delivery potential due to their low viscosity, and the presence of penetration enhancing surfactants and co surfactants. OBJECTIVE: Applying quality by design (QbD) principles, a tazarotene microemulsion formulation for local skin delivery was optimized by creating a control space. MATERIALS AND METHODS: Critical formulation factors (CFF) were oil, surfactant/co-surfactant (SAA/CoS), and water percentages. Critical quality attributes (CQA) were globular size, microemulsion viscosity, tazarotene skin deposition, permeation, and local accumulation efficiency index. RESULTS AND DISCUSSION: Increasing oil percentage increased globular size, while the opposite occurred regarding SAA/CoS, (p = 0.001). Microemulsion viscosity was reduced by increasing oil and water percentages (p < 0.05), due to the inherent high viscosity of the utilized SAA/CoS. Drug deposition in the skin was reduced by increasing SAA/CoS due to the increased hydrophilicity and viscosity of the system, but increased by increasing water due to hydration effect (p = 0.009). Models with very good fit were generated, predicting the effect of CFF on globular size, microemulsion viscosity, and drug deposition. A combination of 40% oil and 45% SAA/CoS showed the maximum drug deposition of 75.1%. Clinical skin irritation study showed that the aforementioned formula was safe for topical use. CONCLUSION: This article suggests that applying QbD tools such as experimental design is an efficient tool for drug product design. PMID- 26133081 TI - Can thiolation render a low molecular weight polymer of just 20-kDa mucoadhesive? AB - The objective was to investigate whether even low-molecular weight polymers (LMWPs) can be rendered mucoadhesive due to thiolation. Interceded by the double catalytic system carbodiimide/N-hydroxysuccinimide, cysteamine was covalently attached to a copolymer, poly(4-styrenesulfonic acid-co-maleic acid) (PSSA-MA) exhibiting a molecular weight of just 20 kDa. Depending on the amount of added N hydroxysuccinimide and cysteamine, the resulting PSSA-MA-cysteamine (PC) conjugates exhibited increasing degree of thiolation, highest being "PC 2300" exhibiting 2300.16 +/- 149.86 MUmol thiol groups per gram of polymer (mean +/- SD; n = 3). This newly developed thiolated polymer was evaluated regarding mucoadhesive, rheological and drug release properties as well from the toxicological point of view. Swelling behavior in 100 mM phosphate buffer pH 6.8 was improved up to 180-fold. Furthermore, due to thiolation, the mucoadhesive properties of the polymer were 240-fold improved. Rheological measurements of polymer/mucus mixtures confirmed results obtained by mucoadhesion studies. In comparison to unmodified polymer, PC 2300 showed 2.3-, 2.3- and 2.4-fold increase in dynamic viscosity, elastic modulus and viscous modulus, respectively. Sustained release of the model drug codeine HCl out of the thiomer was provided for 2.5 h (p < 0.05), whereas the drug was immediately released from the unmodified polymer. Moreover, the thiomer was found non-toxic over Caco-2 cells for a period of 6- and 24-h exposure. Findings of the present study provide evidence that due to thiolation LMWPs can be rendered highly mucoadhesive as well as cohesive and that a controlled drug release out of such polymers can be provided. PMID- 26133082 TI - Thermal, mechanical and drug release characteristics of an acrylic film using active pharmaceutical ingredient as non-traditional plasticizer. AB - The objective of this study was to investigate thermal and mechanical properties as well as in vitro drug release of Eudragit(r) RL (ERL) film using chlorpheniramine maleate (CPM) as either active pharmaceutical ingredient or non traditional plasticizer. Differential scanning calorimeter was used to measure the glass transition temperature (Tg) of 0-100% w/w CPM in ERL physical mixture. Instron testing machine was used to investigate Young's modulus, tensile stress and tensile strain (%) of ERL film containing 20-60% w/w CPM. Finally, a Franz diffusion cell was used to study drug release from ERL films obtained from four formulations, i.e. CRHP0/0, CRHP0/5, CRHP2/0 and CRHP2/5. The Tg of ERL was decreased when the weight percentage of CPM increased. The reduction of the Tg could be described by Kwei equation, indicating the interaction between CPM and ERL. Modulus and tensile stress decreased whereas tensile strain (%) increased when weight percentage of CPM increased. The change of mechanical properties was associated with the reduction of the Tg when weight percentage of CPM increased. ERL films obtained from four formulations could release the drug in no less than 10 h. Cumulative amount of drug release per unit area of ERL film containing only CPM (CRHP0/0) was lower than those obtained from the formulations containing traditional plasticizer (CRHP0/5), surfactant (CRHP2/0) or both of them (CRHP2/5). The increase of drug release was a result of the increase of drug permeability through ERL film and drug solubility based on traditional plasticizer and surfactant, respectively. PMID- 26133083 TI - Metabolic interactions of magnolol with cytochrome P450 enzymes: uncompetitive inhibition of CYP1A and competitive inhibition of CYP2C. AB - Magnolol (MAG; 5,5'-diallyl-2,2'-biphenyldiol) is a major bioactive component of Magnolia officinalis. We investigated the metabolic interactions of MAG with hepatic cytochrome P450 monooxygenase (CYP) through in vitro microsomal metabolism study using human (HLM) and rat liver microsomes (RLM). CYP2C and 3A subfamilies were significantly involved in the metabolism of MAG, while CYP1A subfamily was not in HLM and RLM. The relative contribution of phase I enzymes including CYP to the metabolism of MAG was comparable to that of uridine diphosphate glucuronosyltransferase (UGT) in RLM. Moreover, MAG potently inhibited the metabolic activity of CYP1A (IC50 of 1.62 MUM) and 2C (IC50 of 5.56 MUM), while weakly CYP3A (IC50 of 35.0 MUM) in HLM and RLM. By the construction of Dixon plot, the inhibition type of MAG on CYP activity in RLM was determined as follows: uncompetitive inhibitor for CYP1A (Ki of 1.09-12.0 MUM); competitive inhibitor for CYP2C (Ki of 10.0-15.2 MUM) and 3A (Ki of 93.7-183 MUM). Based on the comparison of the current IC50 and Ki values with a previously reported liver concentration (about 13 MUM) of MAG after its seven times oral administration at a dose of 50 mg/kg in rats, it is suggested that MAG could show significant inhibition of CYP1A and 2C, but not CYP3A, in the in vivo rat system. These results could lead to further studies in clinically significant metabolism mediated MAG-drug interactions. PMID- 26133084 TI - Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain. AB - OBJECTIVE: Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. METHODS: Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 degrees C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software aided image processing. RESULTS: Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% +/- 6.67 after 72 h), improved formulation stability at 4 degrees C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. CONCLUSION: Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer's disease management. PMID- 26133085 TI - In vitro-in vivo correlations: general concepts, methodologies and regulatory applications. AB - The major objective of in vitro-in vivo correlations is to be able to use in vitro data to predict in vivo performance serving as a surrogate for an in vivo bioavailability test and to support biowaivers. Therefore, the aims of this review are: (i) to clarify the factors involved during bio-predictive dissolution method development; and (ii) the elements that may affect the mathematical analysis in order to exploit all information available. This article covers the basic aspects of dissolution media and apparatus used in the development of in vivo predictive dissolution methods, including the latest proposals in this field as well as the summary of the mathematical methods for establishing the in vitro in vivo relationship and their scope and limitations. The incorporation of physiological relevant factors in the in vitro dissolution method is essential to get accurate in vivo predictions. Standard quality control dissolution methods do not necessarily reflect the in vivo behavior, so they rarely are useful for predicting in vivo performance. The combination of physiological based dissolution methods with physiological-based pharmacokinetics models incorporating gastrointestinal variables will lead to robust tools for drug and formulation development, nevertheless their regulatory use for biowaiver application still require harmonization of the mathematical methods proposed and more detailed recommendations about the procedures for setting up dissolution specifications. PMID- 26133086 TI - Neurons without dendrites?--A novel type of neurosecretory cell in locusts. AB - Small-diameter nerves were found that are associated with the lateral peripheral nerves of the unfused abdominal ganglia of locusts. Such small nerves were observed in about 30% of all cases in Locusta migratoria, more than 60% in Schistocerca gregaria. Retrograde staining of these small nerves showed two somata in the posterior, lateral, and ventral region of an abdominal ganglion. These cells give rise to the small nerves that accompany the big lateral nerves and, on their surface, form putative neurohaemal release sites. Astonishingly the cells do not form any dendritic ramifications within the neuropile of the ganglia. PMID- 26133087 TI - Probabilistic Analysis of Localized DNA Hybridization Circuits. AB - Molecular devices made of nucleic acids can perform complex information processing tasks at the nanoscale, with potential applications in biofabrication and smart therapeutics. However, limitations in the speed and scalability of such devices in a well-mixed setting can significantly affect their performance. In this article, we propose designs for localized circuits involving DNA molecules that are arranged on addressable substrates and interact via hybridization reactions. We propose designs for localized elementary logic circuits, which we compose to produce more complex devices, including a circuit for computing the square root of a four bit number. We develop an efficient method for probabilistic model checking of localized circuits, which we implement within the Visual DSD design tool. We use this method to prove the correctness of our circuits with respect to their functional specifications and to analyze their performance over a broad range of local rate parameters. Specifically, we analyze the extent to which our localized designs can overcome the limitations of well mixed circuits, with respect to speed and scalability. To provide an estimate of local rate parameters, we propose a biophysical model of localized hybridization. Finally, we use our analysis to identify constraints in the rate parameters that enable localized circuits to retain their advantages in the presence of unintended interferences between strands. PMID- 26133088 TI - The predictive value of the prealbumin-to-fibrinogen ratio in patients with acute pancreatitis. AB - OBJECTIVE: Early identification of severe acute pancreatitis (SAP) progression is important in acute pancreatitis (AP) treatment. The Ranson, APACHE II and CTSI systems are difficult to use and exhibit limited predictive value. Prealbumin and fibrinogen are acute phase reactants generally used to assess the nutritional statuses and coagulation functions of AP patients, respectively. Here, we explored the value of the combination of these two markers for evaluating AP severity and prognosis. METHODS: One hundred and sixty-nine AP patients, including mild AP (MAP) (n = 101) and severe AP (SAP) patients (n = 68), were enrolled. Their Ranson, APACHE II and CTSI scores, routine laboratory test results, and prealbumin and fibrinogen levels were determined after admission. Multivariate regression analysis was performed to determine the independent predictors of AP severity. ROC curves were generated to determine the suitabilities of prealbumin and fibrinogen levels and the above-mentioned scores for SAP prediction. RESULTS: The SAP patients exhibited higher scores, white blood cell counts, CRP and fibrinogen levels but lower calcium, prealbumin levels and prealbumin/fibrinogen ratio than the MAP patients (p < 0.05). The multivariate regression analysis demonstrated that the prealbumin/fibrinogen ratio was a good predictor of severity and outperformed CRP. The prealbumin/fibrinogen ratio was correlated with CRP, hospitalisation length and complication occurrence in SAP. The ROC curve analyses showed that the prealbumin/fibrinogen ratio exhibited superior sensitivity, specificity, PPV and NPV for SAP prediction over the scoring systems. With a cut-off of 31.70 mg/g, the sensitivity, specificity, PPV and NPV were 76.5%, 94.1%, 89.6% and 85.6%, respectively. CONCLUSIONS: The prealbumin/fibrinogen ratio is a promising predictor of AP severity and prognosis. PMID- 26133089 TI - Estimated glomerular filtration rates through 144 weeks on therapy in HIV-1 infected subjects receiving atazanavir/ritonavir and abacavir/lamivudine or simplified to unboosted atazanavir/abacavir/lamivudine. PMID- 26133090 TI - Misclassification of Breast Imaging Reporting and Data System (BI-RADS) Mammographic Density and Implications for Breast Density Reporting Legislation. AB - USA states have begun legislating mammographic breast density reporting to women, requiring that women undergoing screening mammography who have dense breast tissue (Breast Imaging Reporting and Data System [BI-RADS] density c or d) receive written notification of their breast density; however, the impact that misclassification of breast density will have on this reporting remains unclear. The aim of this study was to assess reproducibility of the four-category BI-RADS density measure and examine its relationship with a continuous measure of percent density. We enrolled 19 radiologists, experienced in breast imaging, from a single integrated health care system. Radiologists interpreted 341 screening mammograms at two points in time 6 months apart. We assessed intra- and interobserver agreement in radiologists'; interpretations of BI-RADS density and explored whether agreement depended upon radiologist characteristics. We examined the relationship between BI-RADS density and percent density in a subset of 282 examinations. Intraradiologist agreement was moderate to substantial, with kappa varying across radiologists from 0.50 to 0.81 (mean = 0.69, 95% CI [0.63, 0.73]). Intraradiologist agreement was higher for radiologists with >=10 years experience interpreting mammograms (difference in mean kappa = 0.10, 95% CI [0.01, 0.24]). Interradiologist agreement varied widely across radiologist pairs from slight to substantial, with kappa ranging from 0.02 to 0.72 (mean = 0.46, 95% CI [0.36, 0.55]). Of 145 examinations interpreted as "nondense" (BI-RADS density a or b) by the majority of radiologists, 82.8% were interpreted as "dense" (BI-RADS density c or d) by at least one radiologist. Of 187 examinations interpreted as "dense" by the majority of radiologists, 47.1% were interpreted as "nondense" by at least one radiologist. While the examinations of almost half of the women in our study were interpreted clinically as having BI-RADS density c or d, only about 10% of examinations had percent density >50%. Our results suggest that breast density reporting based on a single BI-RADS density interpretation may be misleading due to high interradiologist variability and a lack of correspondence between BI-RADS density and percent density. PMID- 26133091 TI - The sexually driven epidemic in youths in China's southwestern border region was caused by dynamic emerging multiple recombinant HIV-1 strains. AB - Dehong prefecture, Yunnan province on China's southwestern border was the gateway of the country's AIDS epidemic. Studies on HIV-1 molecular epidemiology will provide key information on virus transmission dynamics and help to inform HIV prevention strategies. HIV-1 infected youths (age 16-25 years) diagnosed in the continuous 3 months in 2009 to 2012 were enrolled. By means of phylogenetic and statistical analyses, It was showed that two thirds (133/205) of youths in Dehong, of which 74.1% were infected sexually, were infected by uncharacterized recombinant HIV-1 strains. Among them about 59.4% (79/131) were unique recombinant forms (URFs) and 40.6% (54/131) formed 11 transmission clusters, termed potential circulating recombinant forms (pCRFs). The emergence of recombinants was statistically significant related with people of low education, residents outside the capital city of Dehong and being Myanmar residents. It was the first report with ongoing HIV-1 recombinant strains in a sexually driven epidemic area in China. Great efforts should be put on reducing multiple risk exposures behavior in local young people, containing the spread of pCRFs to other regions, and preventing the URFs from evolving into future CRFs. Collaborative prevention across border is needed to better control the local AIDS epidemic. PMID- 26133092 TI - Propofol suppresses proliferation and invasion of glioma cells by upregulating microRNA-218 expression. AB - Propofol (2,6-diisopropylphenol) is a commonly used intravenous anesthetic agent. The present study aimed to assess the effect of propofol on the proliferation and invasion of human glioma cells, and to determine the potential underlying molecular mechanisms. The effects of propofol on U373 glioblastoma cell proliferation, apoptosis and invasion were detected by an MTT assay, caspase-3 activity measurement and a MatrigelTM invasion assay, respectively. MicroRNA (miR)-218 expression and matrix metalloproteinase (MMP)-2 protein expression levels were analyzed by quantitative polymerase chain reaction and western blot analysis, respectively. In addition, miR-218 precursor was transfected into the cells to assess whether overexpression of miR-218 could affect MMP-2 expression. Anti-miR-218 was transfected into the cells to evaluate the role of miR-218 in the effects of propofol on the biological behavior of glioma cells. The results of the present study demonstrated that propofol significantly increased the expression levels of miR-218, inhibited U373 cell proliferation and invasion, and facilitated apoptosis. In addition, treatment with propofol efficiently reduced MMP-2 protein expression levels, and overexpression of miR-218 also decreased MMP 2 protein expression levels. Whereas, neutralization of miR-218 using the anti miR-218 antibody reversed the effects of propofol on the biological behavior of U373 cells, and on the inhibition of MMP-2 protein expression. In conclusion, propofol may effectively suppress proliferation and invasion, and induce the apoptosis of glioma cells, at least partially through upregulation of miR-218 expression. PMID- 26133093 TI - Primary Caregivers' Support for Female Family Members With Breast or Gynecologic Cancer. AB - BACKGROUND: Female patients with cancer depend on loved ones; thus, family support is pivotal to assist patients in successfully adjusting to life with treatment routines. OBJECTIVE: Our study explored the experiences of primary caregivers who provide care and support for female family members with cancer. METHODS: This study used a qualitative phenomenological research approach. Interviews and journaling about the caregiving experience were conducted with the family members of female cancer patients-6 spouses, 11 daughters, 1 son, and 1 younger sister. Data analysis involved Giorgi's 3-step phenomenological analysis method. RESULTS: The central theme of the primary caregivers' supportive care for their female family member with cancer was "being with" her. This was composed of the following themes: "being there for her via efforts," "living through feelings of guilt and anxiety," and "lessons learned from cancer in the family." CONCLUSIONS: This study reveals an integrated picture of family caregivers' supportive caring experiences. By providing both positive and negative aspects of the caregiving experience, the findings in this study will provide a theoretical foundation to develop more successful support programs for family caregivers of female patients with cancer. IMPLICATIONS FOR PRACTICE: Family-oriented education programs need to be developed to include both the family and the patient in the long journey of cancer. The family caregivers' feelings of guilt regarding the cause of the illness and feelings of anxiety about the uncertainty of the illness should be assessed and managed during the course of the patients' treatment and care. PMID- 26133094 TI - Heterogeneity of Relational Backgrounds is Associated With Variation in Non Suicidal Self-Injurious Behavior. AB - Non-suicidal self-injury (NSSI) is a self-destructive behavior of common prevalence in adolescence and young adulthood. Engagement in NSSI has been consistently linked in the literature with perceptions of one's parent-child relationships as negative or invalidating. However, the potential for multiple combinations of such relational characteristics to be associated with varying cognitive and behavioral manifestations of NSSI remains uninvestigated. In the current study, a person-centered approach to studying perceived parent-child relationship quality and NSSI was adopted; functions and behavioral severity of NSSI were then compared across the different relational profiles created. A latent profile analysis in a sample of 264 self-injuring university students (205 females; m(age) = 19.37 years, sd = 1.50) revealed four distinct profiles, two characterized by negative parent-child perceptions and two by positive parent child perceptions. The perceived relational dimensions of these profiles were unique compared to a parallel group of 264 non-self-injurers (207 females; m(age) = 19.27 years, sd = 1.33). Participants reporting negative parent-child relationships endorsed more severe NSSI, and engaged in NSSI to regulate aggressive emotions. In contrast, individuals reporting positive parent-child relationships engaged in less extreme manifestations of NSSI overall, suggesting lower psychological deficits. Findings suggest that, although not all self injurers perceive their relationships with parents negatively, variation in the perception of relational quality is implicated in behavioral and cognitive variation in NSSI engagement. PMID- 26133095 TI - Foreword to 5th International Conference on Whole Body Vibration Injuries held at Academic Medical Center, University of Amsterdam, The Netherlands, 5-7 June 2013. PMID- 26133096 TI - Florida Nurse Leader Survey Findings: Key Leadership Competencies, Barriers to Leadership, and Succession Planning Needs. AB - OBJECTIVE: This study examined barriers to nursing leadership and succession planning needs for nurse leaders in Florida. BACKGROUND: The Florida Action Coalition responded to the call to prepare and enable nurses to lead change to advance health, through a grant supported by the Robert Wood Johnson Foundation and Florida Blue Foundation. METHODS: This is a nurse leader subset of a 56-item statewide survey of actively licensed RNs and advanced RN practitioners in Florida conducted via a cross-sectional, exploratory descriptive research design. RESULTS: Key findings included a description of leadership competencies, barriers, and succession planning practices. Florida nurse leaders are aging and less diverse than the general population and report limited utilization of succession planning by their organizations. CONCLUSIONS: In Florida, attention must be directed to resources and strategies to develop skilled nurse leaders and plan succession. PMID- 26133097 TI - Sitter Reduction Through Mobile Video Monitoring: A Nurse-Driven Sitter Protocol and Administrative Oversight. AB - This article describes the implementation of a mobile video monitoring program, combined with a nursing-driven sitter protocol and administrative oversight, resulting in a significant return on investment over a 2-year period. Program implementation, structures, and processes are described. Financial and quality outcomes are summarized and compared to national benchmarks. PMID- 26133098 TI - Unusual triskelion patterns and dye-labelled GUVs: consequences of the interaction of cholesterol-containing linear-hyperbranched block copolymers with phospholipids. AB - Cholesterol (Ch) linked to a linear-hyperbranched block copolymer composed of poly(ethylene glycol) (PEG) and poly(glycerol) (hbPG) was investigated for its membrane anchoring properties. Two polyether-based linear-hyperbranched block copolymers with and without a covalently attached rhodamine fluorescence label (Rho) were employed (Ch-PEG30-b-hbPG23 and Ch-PEG30-b-hbPG17-Rho). Compression isotherms of co-spread 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1 palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) with the respective polymers were measured on the Langmuir trough and the morphology development of the liquid-condensed (LC) domains was studied by epi-fluorescence microscopy. LC domains were strongly deformed due to the localization of the polymers at the domain interface, indicating a line activity for both block copolymers. Simultaneously, it was observed that the presence of the fluorescence label significantly influences the domain morphology, the rhodamine labelled polymer showing higher line activity. Adsorption isotherms of the polymers to the water surface or to monolayers of DPPC and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), respectively, were collected. Again the rhodamine labelled polymer showed higher surface activity and a higher affinity for insertion into lipid monolayers, which was negligibly affected when the sub-phase was changed to aqueous sodium chloride solution or phosphate buffer. Calorimetric investigations in bulk confirmed the results found using tensiometry. Confocal laser scanning microscopy (CLSM) of giant unilamellar vesicles (GUVs) also confirmed the polymers' fast adsorption to and insertion into phospholipid membranes. PMID- 26133099 TI - Hydrazinonicotinic acid derivatization for selective ionization and improved glycan structure characterization by MALDI-MS. AB - The analysis of glycan is important for understanding cell biology and disease processes because the glycans play a key role in many important biological behaviors, such as cell division, cellular localization, tumor immunology and inflammation. Nevertheless, it is still hard work to analyze glycans by MALDI-MS, which generally stems from the inherent low abundance and the low ionization efficiency of glycans. Moreover, the difficulty in generating informative fragmentations further hinders glycans structure characterization. In this work, hydrazinonicotinic acid (HYNIC) was used as a novel derivatized reagent for improved and selective detection of glycans. Through tagging the reducing terminus of glycans with the diazanyl group of HYNIC, significant enhancement of the ionization efficiency of glycans was achieved. After derivatization, the signal to noise ratio (S/N) of the maltoheptaose was improved by more than one order of magnitude in positive mode. HYNIC derivatization also allowed the sensitive detection of sialylated glycan in negative mode, with a 15 fold enhancement of S/N. Interestingly, it is noteworthy that the HYNIC reagent not only effectively labeled the reducing end of glycans in the presence of tryptic peptides, but also suppressed the ionization of peptides, enabling the direct detection of glycans from glycoprotein without separation. Therefore, analysis of glycans became easier due to the omission of a pre-separation step. Importantly, by using different acid reagents as the catalyst, derivatized product signals corresponding to [M + Na](+) or [M + H](+) were obtained respectively, which yield complementary fragmentation patterns for the structure elucidation of glycans. Finally, more than 40 N-glycans were successfully detected in 10 MUL human serum using this method. PMID- 26133100 TI - One-pot synthesis of spiropyrroloquinoline-isoindolinone and their aza-analogs via the Ugi-4CR/metal-free intramolecular bis-annulation process. AB - This presentation discloses a one-pot synthesis of a series of spiropyrroloquinoline isoindolinone and spiropyrroloquinoline aza-isoindolinone scaffolds. The reaction proceeds by the combination of a Ugi four-component reaction (4CR) and two intramolecular cyclizations under metal-free conditions. The proof of the structures relies on analytical investigation and X-ray crystallography. PMID- 26133101 TI - Expression of the orexin system in the porcine uterus, conceptus and trophoblast during early pregnancy. AB - Orexin A and B are hypothalamic peptides derived from the prepro-orexin (PPO) precursor. Orexins stimulate food intake and arousal. Those peptides bind and activate two G protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Numerous authors have suggested that orexins play an important role in the regulation of the reproductive functions. The objective of the present study was to analyse the presence of and changes in the gene and protein expression pattern of the orexin system in the porcine uterus, conceptus and trophoblast (chorioallantois) during early pregnancy. In the endometrium, the highest PPO and OX1R gene expression was detected on days 15 to 16 of gestation. The OX2R mRNA content in the endometrium was higher on days 10 to 11 and 15 to 16 than on days 12 to 13 and 27 to 28. In the trophoblasts, PPO gene expression was higher on days 30 to 32 than on days 27 to 28. The highest PPO protein content in the endometrium was noted on days 12 to 13. The highest OX1R protein content in the endometrium was detected on days 10 to 11, whereas OX2R protein on days 15 to 16. In the trophoblasts, PPO and OX1R protein levels were more pronounced on days 27 to 28 than on days 30 to 32, but OX2R expression was higher on days 30 to 32. The expression of PPO, OX1R and OX2R was different in the conceptuses and trophoblasts during early pregnancy. Local orexin production and the presence of the specific orexin receptors suggest that the orexin system may participate in the control of porcine reproductive functions by exerting endocrine and auto/paracrine effects on the uterus, conceptuses and trophoblasts during early pregnancy. This study provides the first evidence for the presence of orexins and their receptors in the uteri, conceptuses and trophoblasts in pigs during early pregnancy. The local orexin system is dependent on the stage of pregnancy. PMID- 26133102 TI - Synthesis and characterization of new related substances of the antiarrhythmic drug dronedarone hydrochloride. AB - Two new potential impurities of antiarrhythmic drug substance Dronedarone Hydrochloride together with debutyldronedarone were detected by LC-MS analysis during process development. A successful synthetic strategy for the synthesis of these potential impurities was developed facilitating the access to new impurity reference standards. Their synthesis and characterization are discussed in detail. The availability of these impurity standards allowed cost reduction through the increase of process control. PMID- 26133103 TI - Rapid determination of 1-deoxynojirimycin in Morus alba L. leaves by direct analysis in real time (DART) mass spectrometry. AB - A new method based on a Direct Analysis in Real Time (DART) ionization source coupled with triple quadrupole tandem mass spectrometry has been developed for rapid qualitative and quantitative analyses of 1-deoxynojirimycin (DNJ) in mulberry leaves. Two ions produced from DNJ, [M+H](+) (m/z 164) and [M-2H+H](+) (m/z 162), are observed using DART-MS in the positive ion mode. The peak areas of the two selected ions monitoring (SIM) signals of ([M+H](+) (m/z 164) and [M 2H+H](+) (m/z 162)) are integrated to determine the peak area for quantitative analyses. A reasonable linear regression equation is obtained in the range of 1.01 to 40.50 MUg/mL, with a linear coefficient (R(2)) of 0.996. The limits of detection (LOD) and quantification (LOQ) of the method are 0.25 and 0.80 MUg/mL, respectively. The range of recovery is shown to be 87.73-95.61%. The results derived from the developed DART-MS method are in good agreement with those from the conventional HPLC-FLD method. By contrast, DART-MS in SIM mode is a simple, rapid and high-throughput approach for the determination of the DNJ content in mulberry leaves. The present method is advantageous for the rapid screening of mulberry leaves containing high DNJ contents. PMID- 26133104 TI - Determination of dihydromyricetin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study. AB - Ampelopsis grossedentata (Hand.-Mazz.) W.T. Wang has long been used as a traditional Chinese medicinal herb among the indigenous people in the Yangtze River region of China. Dihydromyricetin (DMY) is the most abundant (approximately 30%) and bioactive constituent in A. grossedentata (Hand.-Mazz.) W.T. Wang, and recent studies have demonstrated its various pharmacological activities. In the present study, a first specific, sensitive, rapid and reliable LC-MS/MS method for the determination of DMY in rat plasma was developed and validated. The plasma samples were prepared with protein precipitation method, and chromatographic separation was performed on a Welch Ultimate XB-C18 column (50 * 2.1 mm, 5 MUm) using a gradient elution with water and acetonitrile. The mass spectrometry (MS) analysis was conducted in negative ionization mode with multiple reaction monitoring (MRM) transitions at m/z 319.1->192.8 for DMY and m/z 609.0->301.2 for rutin (IS). The plasma concentration profiles and pharmacokinetic parameters were analyzed after oral administration of dextroisomer and racemate DMY at the dose of 100 mg/kg in rats. The method validation was conducted over the calibration range of 10.0-5000 ng/ml with the intra- and inter-day precision and accuracy within 12.0% (RSD) and 5.6% (RE). The recoveries, matrix effect and stability under different conditions were all proved acceptable. The values of Tmax, AUC(0-infinity) and Vd were significantly different between the groups of dextroisomer and racemate DMY (P<0.05), and pharmacokinetic results revealed their poor absorptions into blood, probably high tissue distributions and slow elimination processes. The present study will provide helpful information for the further studies and future clinical applications of DMY. PMID- 26133105 TI - An integrated strategy of marker ingredients searching and near infrared spectroscopy rapid evaluation for the quality control of Chinese eaglewood. AB - The application of near infrared spectroscopy (NIRS) in traditional Chinese medicine (TCM) has usually been limited by its blindness to qualitative or quantitative multivariate analysis and because its chemical significance is easily ignored. Here, an integrated technology of ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/Tof) and NIRS was proposed to set up a systematic quality control of Chinese Eaglewood (CE). UPLC-Q/Tof combined with principle compound analysis (PCA) was used to identify the marker ingredients of CE. Four types of highly oxidized 5,6,7,8-tetrahydro-2 (2-phenylethyl) chromones (THPECs) were then identified as potential markers to distinguish the authenticity of the CE. Based on the marker ingredients, the definite wavenumber intervals and spectral pretreatment pattern of NIRS were selected to act as an alternative evaluation technology directed against CE powder samples. Calibration equations were developed from the contents of the four markers, as detected by high performance liquid chromatography (HPLC) and NIRS data, using synergy interval partial least squares (siPLS) algorithm with Leave-One-Out (LOO) cross-validation. Using siPLS regression, satisfactory calibration statistics were obtained for the prediction of the marker ingredients. The correlation coefficient (r) between the predicted and reference results for the test set was used as an evaluation parameter for the models (r>0.9). Hierarchical cluster analysis and partial least squares-discriminant analysis (PLS-DA) were applied to further analyze the quantitative results from NIRS. From this systematic method, 50 CE samples were divided into superior, qualified, unqualified, and fake samples, displaying a more elaborate division than PLS-DA, which is only based on whole NIR spectra or HPLC. This tandem technique of UPLC-Q/Tof and NIRS assessment presented in this work can be used as a rapid evaluation approach for the quality control of complicated herbal medicines. PMID- 26133106 TI - The role of neutral and ionized oxygen defects in the emission of tin oxide nanocrystals for near white light application. AB - Tin oxide (SnO2) nanocrystals (NCs) based phosphor was synthesized by a green chemistry microwave-assisted hydrothermal method at different reactor pressures. The x-ray diffraction analysis showed that a single rutile SnO2 phase with a tetragonal lattice structure was formed. The photoluminescence emission was measured for He-Cd laser excitation at 325 nm and it showed a broad band emission from 400 to 800 nm for all the synthesized reactor pressures. The broad emission spectra were due to the creation of various oxygen and tin defects as confirmed by x-ray photoelectron spectroscopy data. The origin of the emission in the SnO2 NCs is discussed with the help of an energy band diagram. Analysis suggests that the visible emission of SnO2 NCs is due to a transition of an electron from a level close to the conduction band edge to a deeply trapped hole in the SnO2 NCs. The NCs were found to be suitable for warm near white light emission device applications. PMID- 26133107 TI - Low-dose UVB irradiation prevents MMP2-induced skin hyperplasia by inhibiting inflammation and ROS. AB - Skin cancer is one of the most common types of malignancy in the world. UV radiation is known as the primary environmental carcinogen responsible for skin cancer development. However, UV radiation is a ubiquitous substance existing in the environment and the physiological effect of UV radiation is consistently ignored. Therefore, in the present study, the physiological effect of UV radiation on inhibition of skin cancer was investigated. Normal mouse skin was processing by no pre-radiation or pre-radiation of low-dose UV before a medium or high dose of UV radiation. We found that the low-dose pre-radiated mouse skin tissue exhibited low skin inflammation, skin ROS production and consequently low skin epithelial hyperplasia after the medium-dose UV radiation compared with the no pre-radiated mouse. However, this inhibition was not indicated in the high dose UV radiation group after low-dose pre-radiation. Furthermore, western blot analysis and gelatin zymography showed low expression and activation of MMP2 in the skin tissues processed following medium-dose radiation, but not in tissues treated with high-dose radiation after a low-dose pre-radiation. Further investigation of MMP2 inhibitors of TIMP2/TIMP4 showed an upregulated TIMP2 expression, but not TIMP4. Collectively, these data indicate that low-dose pre radiation attenuates the skin inflammation and ROS production induced by medium dose UV radiation and also elevates TIMP2 to withstand MMP2, therefore suppressing skin hyperplasia. The present study indicates a novel concept or prophylactic function of moderate UV radiation as a preventative strategy. PMID- 26133108 TI - Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation. AB - OBJECTIVES: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD). METHODS: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. RESULTS: (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin beta receptor (LTbetaR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes. CONCLUSION: We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression. PMID- 26133109 TI - Download Alert: Understanding Gastroenterology Patients' Perspectives on Health Related Smartphone Apps. AB - OBJECTIVES: The aims of this study were to understand patients' willingness to use different types of health-related smartphone apps and to explore their attitudes on the overall value, usability, feasibility, credibility, intrusiveness, and obtrusiveness of these apps. METHODS: Questionnaires were distributed to adult patients presenting to gastroenterology clinics at an academic medical center. The 25-question survey consisted of 5-point Likert-type scale statements, multiple-choice questions, and open-ended questions. RESULTS: Participants were mainly White (N=94, 78%) and smartphone owners (N=125, 93%). The mean age was 40.8 years (N=121, s.d.=13.2). Participants were willing to use most types of apps unless it monitored their location or social networking activity. Half were less willing to use an app if it required a visible accessory. Most participants were willing to use a health-related app up to 5 min a day indefinitely but unwilling to pay out-of-pocket for it. Participants generally disagreed that an app would be hard to learn how to use, interfere with their daily routine, or be embarrassing to use in public. Overall, participants felt that health-related apps could help them and their doctors better manage their medical problems, but were neutral in trusting their quality. Most worried that personal information used for an app would fall into the wrong hands. CONCLUSION: Gastroenterology patients were willing to use and valued most types of health-related apps. They perceived this technology as feasible, usable, and relatively unobtrusive unless a visible accessory was required. However, many were concerned about their privacy. PMID- 26133110 TI - Cirrhosis is Associated with an Increased 30-Day Mortality After Venous Thromboembolism. AB - OBJECTIVES: Patients with cirrhosis are at increased risk of venous thromboembolism (VTE), but the impact of cirrhosis on the clinical course following VTE is unclear. In a nationwide cohort study, we examined 30-day mortality among patients with cirrhosis and VTE. METHODS: We used Danish population-based health-care databases (1994-2011) to identify patients with incident VTE, i.e., deep venous thrombosis (DVT), pulmonary embolism (PE), and portal vein thrombosis (PVT). Among these, we identified 745 patients with cirrhosis and 3647 patients without cirrhosis (matched on gender, year of birth, calendar year of VTE diagnosis and VTE type). We assessed the 30-day mortality risk among VTE patients with and without cirrhosis, and the mortality rate ratios (MRRs), using an adjusted Cox model with 95% confidence interval. We obtained information on immediate cause of death for patients who died within 30 days after VTE. RESULTS: The 30-day mortality risk for DVT was 7% for patients with cirrhosis and 3% for patients without cirrhosis. Corresponding PE-related mortality risks were 35% and 16%, and PVT-related mortality risks were 19% and 15%, respectively. The adjusted 30-day MRRs were 2.17 (1.24-3.79) for DVT, 1.83 (1.30-2.56) for PE, and 1.30 (0.80-2.13) for PVT. Though overall mortality was higher in patients with cirrhosis than patients without cirrhosis, the proportions of deaths due to PE were similar among patients (25% and 24%, respectively). CONCLUSIONS: Cirrhosis is a predictor for increased short-term mortality following VTE, with PE as the most frequent cause of death. PMID- 26133111 TI - DNA Photosensitization by an "Insider": Photophysics and Triplet Energy Transfer of 5-Methyl-2-pyrimidone Deoxyribonucleoside. AB - The main chromophore of (6-4) photoproducts, namely, 5-methyl-2-pyrimidone (Pyo), is an artificial noncanonical nucleobase. This chromophore has recently been reported as a potential photosensitizer that induces triplet damage in thymine DNA. In this study, we investigate the spectroscopic properties of the Pyo unit embedded in DNA by means of explicit solvent molecular-dynamics simulations coupled to time-dependent DFT and quantum-mechanics/molecular-mechanics techniques. Triplet-state transfer from the Pyo to the thymine unit was monitored in B-DNA by probing the propensity of this photoactive pyrimidine analogue to induce a Dexter-type triplet photosensitization and subsequent DNA damage. PMID- 26133112 TI - Group 1 and 2 cyclic (alkyl)(amino)carbene complexes. AB - The first examples of cyclic (alkyl)(amino)carbene (CAAC) ligands bound to electropositive metal centres (K, Mg, Sr and Ba) have been isolated and characterised. Preliminary studies demonstrate that all complexes are active for polar monomer polymerisation under ambient conditions affording desirable hydroxyl-terminated telechelic polymers. PMID- 26133113 TI - Religiosity aspects in patients with epilepsy. AB - The objectives of this study were to assess religiosity aspects in patients with epilepsy (PWEs) and controls and to determine whether such aspects were related to the samples' clinical, sociodemographic, and QOL-31 data. The Duke Religion Index was administered to 159 adult PWEs and 50 controls. The relationships between the Duke Religion Index and the study variables of the two groups were compared. Intrinsic religiosity (IR) and nonorganizational religiosity (NOR) were higher in PWEs than in controls. Logistic regression showed that being female (p=0.022) and having mesial temporal lobe epilepsy with hippocampus sclerosis (MTLE-HS) (p=0.003) were predictors of high organizational religiosity (OR) and that high NOR was associated with MTLE-HS (p=0.026) and controlled seizures. Further, only MTLE-HS (p=0.002) was predictive of high IR. The Duke Religion Index and QOLIE-31 scores were not related. Different forms of interictal religiosity are related to clinical aspects of epilepsy. PMID- 26133114 TI - Importance of Understanding the Validity and Reliability of Visual Analogue Scales for Rating of Personality--Reply. PMID- 26133115 TI - Paenibacillus populi sp. nov., a novel bacterium isolated from the rhizosphere of Populus alba. AB - A novel aerobic bacterium, designated strain LAM0705(T), was isolated from the rhizosphere of Populus alba in the Peking University Third Hospital. Cells of strain LAM0705(T) were observed to be Gram-stain positive, motile, spore-forming and rod-shaped. The optimal temperature and pH for growth were found to be 30 degrees C and pH 7.5, respectively. Strain LAM0705(T) was found to be able to grow in the presence 0-5 % NaCl (w/v) (optimum 1.0 %). The major fatty acids of strain LAM0705(T) were identified as anteiso-C15:0, C16:0 and iso-C16:0. The dominant polar lipids were found to consist of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The cell wall peptidoglycan of strain LAM0705(T) was found to contain meso-diaminopimelic acid. The predominant menaquinone was identified as MK-7. The G+C content of genomic DNA was found to be 48 mol% when determined by the T m method. The 16S rRNA gene sequence similarity analysis indicated that strain LAM0705(T) is closely related to Paenibacillus agaridevorans DSM 1355(T) and Paenibacillus thailandensis KCTC 13043(T) with 97.8 and 96.1 % sequence similarity, respectively. The DNA-DNA hybridization value between strain LAM0705(T) and P. agaridevorans DSM 1355(T) was 47 +/- 0.8 %. On the basis of its phenotypic, phylogenetic and chemotaxonomic characteristics, strain LAM0705(T) is concluded to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus populi sp. nov. is proposed. The type strain is LAM0705(T) (=ACCC 06427(T) = JCM 19843(T)). PMID- 26133116 TI - Single-incision robotic colectomy (SIRC): Current status and future directions. AB - By combining laparo-endoscopic single-site surgery (LESS) techniques with the da Vinci robotic platform, single-incision robotic colectomy (SIRC) aims to further minimize incision-related complications and improve cosmetic outcomes from the current standard of care, laparoscopic colectomy. While there is limited literature on SIRC, all available reports suggest SIRC to be a safe and feasible procedure in terms of perioperative outcomes. Future research should focus on further clarification of proposed benefits of SIRC such as cosmetics, ergonomics, incidence of incision-related complications, and long-term oncologic outcomes. PMID- 26133117 TI - Lack of an Association between the SDF-1 rs1801157 Polymorphism and Coronary Heart Disease: A Meta-Analysis. AB - Recent studies have shown that the single-nucleotide polymorphism (SNP) rs1801157 in the stromal cell-derived factor (SDF)-1 gene is associated with susceptibility to coronary heart disease (CHD). However, published studies have shown inconsistent results. Therefore, a meta-analysis was carried out to evaluate the association between rs1801157 and CHD in the literature. A systematic literature search was performed using the PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure and Chinese Wan Fang databases. Heterogeneity and publication bias were also evaluated. Seven eligible studies that involved 4656 cases and 2654 controls were finally included in this meta-analysis. Overall, the results showed that the rs1801157 polymorphism was not statistically associated with the risk of CHD under all genetic models but that rs1801157 was associated with decreased susceptibility to myocardial infarction (MI) in subgroup analyses. Moreover, no association was found between rs1801157 and the susceptibility to CHD in either Caucasians or Asians. In conclusion, our meta analysis demonstrated that the rs1801157 polymorphism is not associated with the susceptibility to CHD but may be associated with a decreased risk of MI. However, further large-scale, case-control studies with rigorous designs should be conducted to confirm these conclusions. PMID- 26133118 TI - Bufalin inhibits TGF-beta-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-beta receptors. AB - The epithelial-to-mesenchymal transition (EMT) is a well-known prerequisite for cancer cells to acquire the migratory and invasive capacity, and to subsequently metastasize. Bufalin is one of the major active components of the traditional Chinese medicine Chan Su, and accumulating evidence has shown its anticancer effect in multipe types of cancer. However, the role of bufalin in transforming growth factor-beta (TGF-beta)-induced EMT and migration remains unclear. In the present study, the effect of bufalin on TGF-beta-induced EMT and migration was investigated in human lung cancer A549 cells. TGF-beta induced EMT in A549 cells and increased their migratory ability, which were markedly suppressed by bufalin. Additionally, TGF-beta-induced upregulation of Twist2 and zinc finger E-box binding homeobox 2 (ZEB2), as well as the phosphorylation of Smad2 and Smad3 were also inhibited by bufalin. However, the Smad-independent signaling pathways were not affected. Further analysis showed that the TGF-beta receptor I (TbetaRI) and TGF-beta receptor II (TbetaRII) were downregulated in the presence of bufalin. Pretreatment with SB431542, a potent inhibitor of the phosphorylation of TbetaRI, significantly attenuated TGF-beta-induced EMT, mimicking the effect of bufalin on A549 cells. Taken together, these results suggest that bufalin suppresses TGF beta-induced EMT and migration by downregulating TbetaRI and TbetaRII in A549 cells. PMID- 26133119 TI - Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core. AB - The proteasome is a highly regulated protease complex fundamental for cell homeostasis and controlled cell cycle progression. It functions by removing a wide range of specifically tagged proteins, including key cellular regulators. Here we present the structure of the human 20S proteasome core bound to a substrate analogue inhibitor molecule, determined by electron cryo-microscopy (cryo-EM) and single-particle analysis at a resolution of around 3.5 A. Our map allows the building of protein coordinates as well as defining the location and conformation of the inhibitor at the different active sites. These results open new prospects to tackle the proteasome functional mechanisms. Moreover, they also further demonstrate that cryo-EM is emerging as a realistic approach for general structural studies of protein-ligand interactions. PMID- 26133120 TI - Family member deaths across adulthood predict Alzheimer's disease risk: The Cache County Study. AB - OBJECTIVES: Parental death during childhood, and offspring and spouse death during adulthood have individually been associated with faster cognitive decline and higher Alzheimer's disease (AD) risk in late life. However, the cumulative effect of childhood and adulthood family deaths on AD risk among different age cohorts has not been studied. METHODS: To examine these associations, this prospective cohort study uses a population-based sample of 4545 initially non demented participants (56.7% female; age M = 75.0/SD = 6.9 years) observed at four triennial waves, linked with objective Utah Population Database data on cumulative mother, father, sibling, spouse, and offspring death experienced during childhood and adulthood. Cox regression modeled survival time from baseline interview to AD onset, as a function of family deaths during childhood or adulthood, among different age groups, along with gender and presence of epsilon4 allele at apolipoprotein E (APOE) polymorphic genetic locus. RESULTS: Age group significantly moderated the relationship between family death and AD; among persons aged 65-69 years at baseline (children of the Great Depression), those exposed to 3-4 deaths and 5+ deaths during adulthood exhibited a doubling of AD risk (adjusted hazard ratio, aHR = 2.25, p = .038, and aHR = 2.72, p = .029), while among persons aged 80 years and older, those exposed to 3-4 deaths during adulthood exhibited lower AD risk (HR = 0.539, p = 0.014). In a combined model of childhood and adulthood deaths, these findings persisted. CONCLUSIONS: Results suggest a cohort effect in the link between family member deaths during adulthood and AD risk later in life. PMID- 26133122 TI - Hepatic myeloid-derived suppressor cells in cancer. AB - Myeloid-derived suppressor cells are key components of tumor-induced immune suppression. They are composed of a heterogeneous population of immature myeloid cells that abrogates innate and adaptive immune responses. Myeloid-derived suppressor cells accumulate not only in peripheral blood, secondary lymphoid organs and tumors, but also in the liver in preclinical tumor models and in hepatocellular carcinoma patients. The liver, continuously exposed to food and microbial antigens from the intestine, avoids autoimmune damage through the use of specialized mechanisms of immune tolerance. In the context of cancer, myeloid derived suppressor cells profit the intrinsic tolerogenic properties of the liver to accumulate and exert various immune-suppressive and tumor-promoting mechanisms which go from inducing immune cell dysfunction to supporting the generation of liver metastases. In this review, we seek to describe the phenotype, function, accumulation and therapeutic targeting of hepatic myeloid-derived suppressor cells both in preclinical settings and in the context of human hepatocellular carcinoma. PMID- 26133121 TI - An Act of Balance Between Adaptive and Maladaptive Immunity in Depression: a Role for T Lymphocytes. AB - Historically the monoaminergic neurotransmitter system, in particular the serotonergic system, was seen as being responsible for the pathophysiology of major depressive disorder (MDD). With the advent of psychoneuroimmunology an important role of the immune system in the interface between the central nervous systems (CNS) and peripheral organ systems has emerged. In addition to the well characterised neurobiological activities of cytokines, T cell function in the context of depression has been neglected so far. In this review we will investigate the biological roles of T cells in depression. Originally it was thought that the adaptive immune arm including T lymphocytes was excluded from the CNS. It is now clear that peripheral naive T cells not only carry out continuous surveillance within the brain but also maintain neural plasticity. Furthermore animal studies demonstrate that regulatory T lymphocytes can provide protection against maladaptive behavioural responses associated with depression. Psychogenic stress as a major inducer of depression can lead to transient trafficking of T lymphocytes into the brain stimulating the secretion of certain neurotrophic factors and cytokines. The separate and combined mechanism of CD4 and CD8 T cell activation is likely to determine the response pattern of CNS specific neurokines and neurotrophins. Under chronic stress-induced neuroinflammatory conditions associated with depression, T cell responses may become maladaptive and can be involved in neurodegeneration. Additionally, intracellular adhesion and MHC molecule expression as well as glucocorticoid receptor expression within the brain may play a role in determining T lymphocyte functionality in depression. Taken together, T lymphocyte mechanisms, which confer susceptibility or resilience to MDD, are not yet fully understood. Further insight into the cellular and molecular mechanisms which balance the adaptive and maladaptive roles of T lymphocytes may provide a better understanding of both the neuro- degenerative and -regenerative repair functions as present within the neuroimmune network during depression. Furthermore T cells may be important players in restoration of normal behaviour and immune cell homeostasis in depression. PMID- 26133123 TI - Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs. AB - Human hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide particularly in Asia. Deregulation of cellular energetics was recently included as one of the cancer hallmarks. Compounds that target the mitochondria in cancer cells were proposed to have therapeutic potential. Biguanide drugs which inhibit mitochondrial complex I and repress mTOR signaling are clinically used to treat type 2 diabetes mellitus patients (T2DM) and were recently found to reduce the risk of HCC in T2DM patients. However, whether alteration of energy metabolism is involved in regulating the sensitivity of HCC to biguanide drugs is still unclear. In the present study, we treated four HCC cell lines with mitochondrial inhibitors (rotenone and oligomycin) and biguanide drugs (metformin and phenformin), and found that the HCC cells which had a higher mitochondrial respiration rate were more sensitive to these treatments; whereas the HCC cells which exhibited higher glycolysis were more resistant. When glucose was replaced by galactose in the medium, the altered energy metabolism from glycolysis to mitochondrial respiration in the HCC cells enhanced the cellular sensitivity to mitochondrial inhibitors and biguanides. The energy metabolism change enhanced AMP-activated protein kinase (AMPK) activation, mTOR repression and downregulation of cyclin D1 and Mcl-1 in response to the mitochondrial inhibitors and biguanides. In conclusion, our results suggest that increased mitochondrial oxidative metabolism upregulates the sensitivity of HCC to biguanide drugs. Enhancing the mitochondrial oxidative metabolism in combination with biguanide drugs may be a therapeutic strategy for HCC. PMID- 26133124 TI - Peribulbar versus retrobulbar anaesthesia for cataract surgery. AB - BACKGROUND: Cataract is a major cause of blindness worldwide. Unless medically contraindicated, cataract surgery is usually performed under local (regional) anaesthesia. Local anaesthesia involves the blockage of a nerve subserving a given part of the body. It involves infiltration of the area around the nerve with local anaesthetic. The two main approaches in the eye are retrobulbar and peribulbar. There is debate over whether the peribulbar approach provides more effective, safer anaesthesia for cataract surgery than retrobulbar block. OBJECTIVES: The objective of this review was to assess the effects of peribulbar anaesthesia (PB) compared to retrobulbar anaesthesia (RB) on pain scores, ocular akinesia, patient acceptability and ocular and systemic complications. SEARCH METHODS: In the previous version of our review, we searched the databases until December 2007. In this updated version, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (March 2015); MEDLINE (1960 to March 2015); and EMBASE (1980 to March 2015). SELECTION CRITERIA: We included randomized controlled clinical trials comparing peribulbar anaesthesia and retrobulbar anaesthesia for cataract surgery. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted trial authors for additional information, study methodology and missing data. We carried out a descriptive narrative of results as the included studies used varied methods for reporting the outcomes. We performed a subgroup analysis for globe akinesia. MAIN RESULTS: We included six trials involving 1438 participants. Three of the six trials had adequate sequence generation while all the trials had unclear allocation concealment There was no evidence of any difference in pain perception during surgery with either retrobulbar or peribulbar anaesthesia. Both were largely effective. There was no evidence of any difference in complete akinesia or the need for further injections of local anaesthetic. Conjunctival chemosis was more common after peribulbar block (relative risk (RR) 2.11, 95% confidence interval (CI) 1.46 to 3.05) and lid haematoma was more common after retrobulbar block (RR 0.36, 95% CI 0.15 to 0.88). Retrobulbar haemorrhage was uncommon and occurred only once, in a patient who had a retrobulbar block. AUTHORS' CONCLUSIONS: There is little to choose between peribulbar and retrobulbar block in terms of anaesthesia and akinesia during surgery measuring acceptability to patients, need for additional injections and development of severe complications. Severe local or systemic complications were rare for both types of block. PMID- 26133125 TI - Effects of the Visual Exercise Environments on Cognitive Directed Attention, Energy Expenditure and Perceived Exertion. AB - Green exercise research often reports psychological health outcomes without rigorously controlling exercise. This study examines effects of visual exercise environments on directed attention, perceived exertion and time to exhaustion, whilst measuring and controlling the exercise component. Participants completed three experimental conditions in a randomized counterbalanced order. Conditions varied by video content viewed (nature; built; control) during two consistently ordered exercise bouts (Exercise 1: 60% VO2peakInt for 15-mins; Exercise 2: 85% VO2peakInt to voluntary exhaustion). In each condition, participants completed modified Backwards Digit Span tests (a measure of directed attention) pre- and post-Exercise 1. Energy expenditure, respiratory exchange ratio and perceived exertion were measured during both exercise bouts. Time to exhaustion in Exercise 2 was also recorded. There was a significant time by condition interaction for Backwards Digit Span scores (F2,22 = 6.267, p = 0.007). Scores significantly improved in the nature condition (p < 0.001) but did not in the built or control conditions. There were no significant differences between conditions for either perceived exertion or physiological measures during either Exercise 1 or Exercise 2, or for time to exhaustion in Exercise 2. This was the first study to demonstrate effects of controlled exercise conducted in different visual environments on post-exercise directed attention. Via psychological mechanisms alone, visual nature facilitates attention restoration during moderate-intensity exercise. PMID- 26133126 TI - Breastfeeding Rates and Growth Charts--the Zhejiang Infant Feeding Trial. AB - A randomised control trial was undertaken in Hangzhou, China, to study the influence of the growth chart used on breastfeeding rates. Mothers with infants who were being fully breastfed at 6 weeks after birth (n = 1602) were invited to participate in the trial; 1415 agreed to participate and 1295 completed the study. Two growth charts were used, one that was heavier for the first six months of life (Chart A, n = 686) and a lighter growth chart (Chart B, n = 609). Mothers were interviewed and infants measured at 6 weeks and 3, 4, 5 and 6 months after delivery. At 6 months the full breastfeeding rates were 18.1% in the group using the heavier growth chart compared to 22.8% in the lighter growth chart group. After adjusting for potential confounders this difference remained significant (aOR 1.41, 95% confidence intervals 1.02, 1.93). These results suggest that breastfeeding rates may be influenced by the type of growth chart used. Mothers who perceive that their infants are not growing adequately (i.e., using the heavier charts) may introduce other foods to their infants earlier than mothers using the lighter chart. While a larger trial is required to confirm the results, in the interim it is suggested that if heavier growth charts are used, a lower percentile line could be used to assess adequacy of growth. PMID- 26133127 TI - Extremely Low Frequency Magnetic Field Exposure and Parkinson's Disease--A Systematic Review and Meta-Analysis of the Data. AB - OBJECTIVE: To examine the association between occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and Parkinson's disease. METHODS: We systematically searched publications reporting risk estimates of Parkinson's disease in workers exposed to ELF-MF. Summary relative risks were obtained with random effects meta-analysis. RESULTS: We included 11 studies. To assign exposure, four studies evaluated occupational records, four used census, interview or questionnaire information and three used death certificates. Risk of Parkinson's disease was not elevated in workers exposed to ELF-MF with a summary relative risk of 1.05, 95% CI 0.98-1.13. CONCLUSIONS: Overall, there was no evidence that the exposure to ELF-MF increases the risk of Parkinson's disease. PMID- 26133128 TI - Cross-Sectional Study of Hepatitis A Virus Infection in the Pantanal Population before Vaccine Implementation in Brazil: Usage of Non-Invasive Specimen Collection. AB - Population-based prevalence studies are essential tools for screening of hepatitis A and provide important data on susceptible groups. However, surveillance in isolated communities is difficult because of the limited access to these areas and the need for blood sample collection. This study aimed to determine the anti-HAV prevalence using oral fluid samples to provide an alternative tool for epidemiological studies that might be useful for vaccination related decisions. The study population was composed of 224 volunteers from South Pantanal, aged 3 to 86 years old. This study was performed using oral fluids, previously standardized for anti-HAV antibody detection, which were collected using a ChemBio device. Eluates were tested using modified commercial EIA to detect anti-HAV antibodies. The overall prevalence was 79.1%, corresponding to 178 reactive EIA tests out of 224 samples. The age stratified data revealed a prevalence of 47.8% between 0-10 years, 84% in 11-20 years and 91.9% in subjects older than 21 years. Results indicate that hepatitis A prevalence was higher in adolescents and adults, corroborating the literature reports. Thus, oral fluid samples could replace serum in HAV epidemiological studies in isolated communities as they are efficient at detecting anti-HAV antibodies. PMID- 26133129 TI - Cost-Effectiveness of a New Nordic Diet as a Strategy for Health Promotion. AB - Inappropriate diets constitute an important health risk and an increasing environmental burden. Healthy regional diets may contribute to meeting this dual challenge. A palatable, healthy and sustainable New Nordic diet (NND) based on organic products from the Nordic region has been developed. This study assesses whether a large-scale introduction of NND is a cost-effective health promotion strategy by combining an economic model for estimating the utility-maximizing composition of NND, a life cycle assessment model to assess environmental effects of the dietary change, and a health impact model to assess impacts on the disease burden. Consumer expenditure for food and beverages in the NND is about 16% higher than currently, with the largest relative difference in low-income households. Environmental loads from food consumption are 15%-25% lower, and more than 18,000 disability-adjusted life years (DALY) will be saved per year in Denmark. NND exhibits a cost-effectiveness ratio of about ?73,000-94,000 per DALY saved. This cost-effectiveness improves considerably, if the NND's emphasis on organic and Nordic-origin products is relaxed. PMID- 26133130 TI - Association Between Geographic Elevation, Bone Status, and Exercise Habits: The Shimane CoHRE Study. AB - In recent years, there has been growing interest in the association between the residential environment and health. The association between residential environment (i.e., geographic elevation) and bone status is unknown. Furthermore, these associations could differ by exercise habits due to the chronically greater daily activity caused by steep slopes in mountainous areas. The aim of this study was to test whether the association between bone status of elderly people measured using quantitative ultrasound (QUS) and elevation varied according to the exercise habits in a mountainous area population. Data were collected from a cross-sectional study conducted during 2012-2013. QUS value was expressed as a proportion of the young adult mean (%YAM), with higher scores donating better bone status. After excluding subjects with missing data, we analyzed the data for 321 men and 500 women. Our results indicate that %YAM was not associated with elevation among men, or among women with exercise habits. However, elevation was associated with %YAM among women without exercise habits. Our results highlight the importance of considering residential environment and exercise habits when establishing promotion strategies to maintain bone status of the elderly people who live in rural mountainous areas. PMID- 26133131 TI - Toxicity and Bioaccumulation of Heavy Metals in Spinach (Spinacia oleracea) Grown in a Controlled Environment. AB - The impact of heavy metal toxicity on the shoot and root lengths, total protein, fiber characteristics, moisture content and nutrient composition of spinach (Spinacia oleracea) was evaluated. Plants were grown in pots containing soil and treated with different concentrations (mg/kg) of lead (Pb; 300, 400 and 500), cadmium (Cd; 0.5, 1 and 1.5) and zinc (Zn; 250, 500, and 700) as well as mixtures of Cd and Pb (0.5/300, 1/400, 1.5/500), Cd and Zn (0.5/250, 1/500, 1.5/700), and Pb and Zn (300/250, 400/500, 500/700). Soil contaminated by long-term irrigation with wastewater containing heavy metals was simulated. An increase in concentrations of heavy metals both individually and as mixtures significantly (p < 0.05) reduced the growth parameters and nutrient contents of S. oleracea. The uptake patterns of heavy metals in mixtures showed antagonistic impacts on each other. The toxicities of the mixtures Cd and Pb, Cd and Zn as well as Pb and Zn were higher than those observed in separate heavy metal applications but less than their additive sums. The toxicity caused by individual heavy metals was the highest for Cd followed by Pb and Zn. The highest toxicity was observed in plants grown in soil contaminated by Cd and Pb. PMID- 26133132 TI - Sexual Health of Polish Athletes with Disabilities. AB - The purpose of this study was to determine sexual functioning of Polish athletes with disabilities (including paralympians). The study encompassed 218 people with physical disabilities, aged between 18 and 45 (149 men and 69 women). The entire research population was divided into three groups: Polish paralympians (n = 45), athletes with disabilities (n = 126) and non-athletes with disabilities (n = 47). The quality of sexual life of Polish paralympians was measured by using the Polish version of Female Sexual Function Index and International Index of Erectile Function. Clinically significant erectile dysfunctions were most often diagnosed in non-athletes (83.33%) with 50% result of severe erectile dysfunctions, followed by athletes and paralympians with comparable results of 56.98% and 54.17% respectively (p = 0.00388). Statistically significant clinical sexual dysfunctions concerned lubrication, orgasm as well as pain domains, and prevailed among female non-athletes (68.42%, 68.42% and 57.89%). Practising sports at the highest level has a favourable effect on the sexuality of men and women with physical disabilities. Men with physical disabilities manifest more sexual disorders than women, an aspect which should be considered by health-care professionals working with people with disabilities. PMID- 26133133 TI - Two-Year Monitoring of Water Samples from Dam of Iskar and the Black Sea, Bulgaria, by Molecular Analysis: Focus on Mycobacterium spp. AB - The coast of the Bulgarian Black Sea is a popular summer holiday destination. The Dam of Iskar is the largest artificial dam in Bulgaria, with a capacity of 675 million m3. It is the main source of tap water for the capital Sofia and for irrigating the surrounding valley. There is a close relationship between the quality of aquatic ecosystems and human health as many infections are waterborne. Rapid molecular methods for the analysis of highly pathogenic bacteria have been developed for monitoring quality. Mycobacterial species can be isolated from waste, surface, recreational, ground and tap waters and human pathogenicity of nontuberculose mycobacteria (NTM) is well recognized. The objective of our study was to perform molecular analysis for key-pathogens, with a focus on mycobacteria, in water samples collected from the Black Sea and the Dam of Iskar. In a two year period, 38 water samples were collected-24 from the Dam of Iskar and 14 from the Black Sea coastal zone. Fifty liter water samples were concentrated by ultrafiltration. Molecular analysis for 15 pathogens, including all species of genus Mycobacterium was performed. Our results showed presence of Vibrio spp. in the Black Sea. Rotavirus A was also identified in four samples from the Dam of Iskar. Toxigenic Escherichia coli was present in both locations, based on markers for stx1 and stx2 genes. No detectable amounts of Cryptosporidium were detected in either location using immunomagnetic separation and fluorescence microscopy. Furthermore, mass spectrometry analyses did not detect key cyanobacterial toxins. On the basis of the results obtained we can conclude that for the period 2012-2014 no Mycobacterium species were present in the water samples. During the study period no cases of waterborne infections were reported. PMID- 26133134 TI - Comparison of the Cumulative Incidence Rates of Coal Workers' Pneumoconiosis between 1970 and 2013 among Four State-Owned Colliery Groups in China. AB - The purpose of this study was to identify differences in the incidence characteristics of coal workers' pneumoconiosis (CWP) based on data from four large state-owned colliery groups of China, by comparing the cumulative incidence rates of CWP. We investigated 87,904 coal workers from the Datong, Kailuan, Fuxin, and Tiefa Colliery Groups, who were exposed to dust for at least 1 year. The cumulative incidence rate of CWP was calculated with the life-table method and stratified analysis among coal workers with different occupational categories during different years of first dust exposure. Our results showed the cumulative incidence rate of Datong was higher than that of any other colliery group among workers with different occupational categories during different years of first dust exposure. For Datong workers who started their dust exposure in the 1970s, the cumulative incidence rates of CWP among tunneling, mining, combining, and helping workers were 34.77%, 10.20%, 34.59%, and 4.91% during the observed time of 34 years, respectively. For those in the 1980s, the cumulative incidence rates were 32.29%, 13.51%, 2.98%, and 0.47%, respectively. The cumulative incidence rates of Fuxin and Tiefa were the lowest. In conclusion, the Datong colliery has the highest cumulative incidence rate of CWP among the four studied collieries, followed by Kailuan. The cumulative incidence rates of Fuxin and Tiefa were the lowest. Additional dust-proofing measures for decreasing dust concentrations are still necessary. PMID- 26133135 TI - Membranes and Bone Substitutes in a One-Stage Procedure for Horizontal Bone Augmentation: A Histologic Double-Blind Parallel Randomized Controlled Trial. AB - The aim of this histologic, double-blind, parallel, randomized controlled trial was to compare anorganic bone mineral-collagen membranes (BB) and betatricalcium phosphate-pericardium collagen membranes (CJ) in a one-stage procedure for horizontal bone augmentation. A biopsy was performed in the regenerated area at abutment connection 6 months after surgery. Five patients were assigned and treated with the BB combination and five patients were treated with the CJ combination. At abutment connection, 6 months after grafting, no significant differences were evident in the histomorphometric comparisons, even if the percentage of residual graft, using the marrow spaces and soft tissue as a reference, tended to be greater in the CJ group (P = .0759). PMID- 26133136 TI - Clinical and Laboratory Steps for Fabricating a Complete-Arch Fixed Prosthesis Using CAD/CAM. AB - The fabrication of a full-arch maxillary prosthesis has been associated with several prosthetic complications and difficulties. Even though it has been reported that phonetics, esthetics, and proper lip support are difficult to achieve, there is a scarcity in the literature regarding the clinical and laboratory procedures necessary to minimize these complications. This article provides clinical and laboratory steps that may enable the clinician to achieve more predictable restorative results when using computer-aided design/computer assisted manufacture (CAD/CAM) to fabricate a full-arch maxillary implant supported prosthesis. The technique presented here describes the use of an implant-retained diagnostic wax-up that is subsequently duplicated to an interim polymethylmethacrylate prosthesis using CAD/CAM before fabricating the definitive restoration. PMID- 26133137 TI - An Evaluation of Antibiotic Use in Periodontal and Implant Practices. AB - In past decades, warnings about overprescription and misuse of antibiotics- which are now considered to be responsible for antimicrobial resistance, allergies, ineffectiveness, and suprainfections-have been made to both medical and dental clinicians. To help assess the antibiotic prescribing habits of dentists, a survey was created and emailed through the Survey Monkey tool to 102 randomly selected board-certified periodontists. Each was asked to answer multiple-choice questions regarding their use of an antibiotic protocol in 10 specific periodontal or implant-related clinical circumstances. This group of practitioners and the 10 clinical circumstances were chosen to limit the wide variety of clinical conditions treated by dentists and to narrow the scope of variables when antibiotics are considered. All 102 participants returned the questionnaire, and 96% to 100% of respondents reported that they had treated 8 of the 10 circumstances, with 89.9% and 80.8% having treated the other two conditions listed in the survey; this allowed subsequent questioning of the respondents on their antibiotic prescribing protocols. Although the validity of antibiotics for dental procedures may be questioned based on present information, as many as 50% or more of the dentists answering the survey prescribed antibiotics. The prescription, initiation, and duration of antibiotics varied considerably in many of the 10 specific circumstances, including treatment of acute and chronic periodontitis, sinus or ridge augmentation, and immediate or delayed implant placement. Based on the results of the survey, it was obvious that definitive guidelines and protocols are needed as well as expanded postgraduate training regarding antibiotic use. PMID- 26133138 TI - Treatment of Multiple Adjacent Miller Class III Gingival Recessions with a Modified Tunnel Technique: A Case Series. AB - Modified coronally advanced tunnel (MCAT) technique with connective tissue graft (CTG) was used in treating multiple adjacent Miller Class III gingival recessions in nine patients. Clinical evaluations were recorded at baseline and 12 months after surgery. The results showed that 50% of complete root coverage and 78% of mean root coverage were attained 1 year after surgery and interdental space fill was 73% at 12 months. The study demonstrated that CTG using the MCAT technique may be an efficient way to treat multiple adjacent Miller Class III gingival recessions, especially when aiming for interdental space fill. Success, however, seems to be related to the amount of tissue present initially. PMID- 26133139 TI - Human Histologic Analysis of an Immediately Loaded Single-Tooth Mandibular First Molar Implant. AB - The crestal bone level around an immediately loaded contemporary hybrid implant with a multisurface topography was examined 8 weeks after implant placement and loading. Histologic analysis showed tight contact between the implant surface and surrounding bone, and demonstrated radiographic and histologic features of successful osseointegration. Very high bone-toimplant contact without epithelial downgrowth was noted. The buccal and lingual bone levels coincided with the original bone relationship to the implant shoulder at the time of implant placement, with no signs of resorption. PMID- 26133140 TI - The Dual Function of a Dermal Allograft in Immediate Implant Therapy. AB - Immediate implant placement often requires tissue augmentation simultaneously. Both hard and soft tissue grafting can improve long-term physiologic and esthetic outcomes. Bone replacement grafts are frequently combined with barrier membranes (guided bone regeneration [GBR]). When these materials are resorbable, they are often composed of collagen or synthetic polymers. These techniques do not address the need for soft tissue augmentation, and harvesting of autogenous soft tissue grafts is required. The use of a dermal allograft composed of natural, non-cross linked collagen eliminates the need for the second surgical site to harvest autogenous soft tissue. This article demonstrates the dual functionality of a dermal allograft serving as both a GBR membrane and a biologically incorporated soft tissue biomaterial in immediate implant therapy. PMID- 26133141 TI - A Titanium Mesh and Particulate Allograft for Vertical Ridge Augmentation in the Posterior Mandible: A Pilot Study. AB - This preliminary study was designed to test the clinical efficacy of a modified Ti-mesh combined with particulate allograft for vertical ridge augmentation (VRA). Five healthy patients with vertical ridge deficiency in the posterior mandible were recruited. Preoperative width of the keratinized mucosa (KM) and mucosal thickness (MT) were measured. Cone beam computed tomography (CBCT) scans were taken preoperatively, immediately, and 5 months after VRA. The amount of vertical bone gain was measured on CBCT scans. Bone core biopsies were taken for histomorphometric examinations. The mean +/- standard deviation KM on the facial and lingual sides was 3.9 +/- 1.7 mm and 3.3 +/- 1.3 mm, respectively. The mean thickness of the flaps, measured at the facial, lingual, and crestal sites, was 2.9 +/- 0.8 mm, 1.8 +/- 0.8 mm, and 3.2 +/- 1.2 mm, respectively. The mean vertical gain was 3.4 +/- 1.9 mm when only the sites with the greatest vertical defect in each subject were studied. Histometric analysis of the bone cores revealed that percentages of the soft tissue, residual allograft, and new bone were 42.2% +/- 10.0%, 25.2% +/- 13.5%, and 32.6% +/- 4.9%. The use of a Ti-mesh and particulate allograft may be a viable option for vertical augmentation of sites with slight to moderate ridge deficiency. PMID- 26133142 TI - Comparison of Direct and Indirect Techniques to Develop Customized Implant Impression Copings: A Pilot Study. AB - The aim of this pilot study was to compare a direct and an indirect technique for fabricating customized impression copings. The accuracy of these techniques to capture the tissue contours that have been developed using implant-supported fixed interim restorations (ISFIRs) in single implants for their esthetic value were evaluated. Five patients presenting with maxillary central incisor ISFIRs were enrolled in the study. Customized impression copings were fabricated using a direct and an indirect technique. Specimens of experimental (direct and indirect technique) and control groups (ISFIR) were compared in terms of linear measurements on their buccolingual (BL) and mesiodistal (MD) dimensions at three different levels: platform, middle, and gingival margin. Statistically significant differences were detected between the control group and the direct technique specimens on both the gingival margin and middle levels (P < .05). Between the direct and indirect techniques, statistically significant differences were found in their MD and BL dimensions at the gingival margin level (G-MD, G BL) and the buccolingual dimension at the middle level (M-BL) (P < .05). The indirect technique used for the fabrication of customized implant impression copings seems to be more accurate in capturing the profile of the ISFIR at all three levels (platform, middle, and gingival margin). The direct technique is accurate only at the platform level. PMID- 26133143 TI - Success of Unsplinted Implant-Retained Removable Mandibular and Maxillary Overdentures: A Retrospective Study of Consecutive Cases. AB - Implant-retained overdentures have been provided on both splinted and freestanding implants. For the mandible, a long history shows that both approaches can be successful over the long term. For the maxilla, many clinicians prefer to splint the implants because of concerns about softer bone quality and insufficient data supporting the use of freestanding overdenture abutments. However, a few investigations have found survival rates for unsplinted maxillary overdentures to be comparable to those for splinted ones. The present study analyzed records of consecutive patients who were treated with unsplinted maxillary and mandibular overdentures and followed for 4 to 107 months. A total of 31 overdentures were identified, 15 maxillary and 16 mandibular, supported by 129 implants. All the overdentures, along with all the implants, survived throughout the follow-up period. PMID- 26133144 TI - Fate of a Bovine-Derived Xenograft in Maxillary Sinus Floor Elevation After 14 Years: Histologic and Radiologic Analysis. AB - This report assesses the results following sinus floor augmentation performed 14 years previously in which bovine bone xenograft material was used without implant insertion. After sinus floor augmentation, using a 20:80 mixture of autogenous bone and inorganic bovine bone material (Bio-Oss), bone biopsy specimens were taken from the grafted site, processed with Donath's sawing and grinding technique, stained with toluidine blue, and mounted on high-sensitivity plates for histology and microradiography. Histologic and microradiographic analysis showed the ingrowth of newly formed bone into the graft with interspersed residual Bio-Oss granules. The percentage of Bio- Oss and newly formed bone was 10.18% and 9.32%, respectively, within a total surface area of 70.61 mm2 at the site of the corresponding missing first molar, and the percentage of Bio-Oss and newly formed bone was 11.47% and 14.96%, respectively, within a total surface area of 63.92 mm2 at the corresponding missing second molar. The newly formed bone was vital without signs of resorption. This study produced strong evidence that newly formed bone was distributed throughout the bone substitute material around all of its granules and that the grafted site consisted of vital bone even in its central parts. The differences in degradation rate and/or whether the effect of bone graft substitutes alone and/ or in combination with other types, shapes, and sizes of graft materials needs further clinical investigation, especially in regard to long-term changes. PMID- 26133145 TI - LipStaT: The Lip Stabilization Technique- Indications and Guidelines for Case Selection and Classification of Excessive Gingival Display. AB - Excessive gingival display (EGD) is an esthetic concern affecting a substantial portion of the population. Identification, diagnosis, and classification of all factors resulting in EGD are imperative for its appropriate management. While many authors have described these factors individually, the authors of the current study propose a simple classification, which includes major etiologies of EGD. Where EGD is associated with maxillary lip hypermobility, a proposal of a subclass 1-3 is offered. A "decision-making tree" to help guide clinicians in managing EGD is included. A detailed description of the lip stabilization technique (LipStaT), including indications, surgical guidelines, postsurgical management, and clinical cases with long-term follow-up, is presented. PMID- 26133146 TI - The ABC Protocol in the Esthetic Zone: A Comprehensive Surgical and Prosthetic Approach. AB - The purpose of this article is to present a surgical and restorative protocol for the replacement of missing teeth in the esthetic zone. The ABC protocol consists of digitally guided implantation, autogenous bone graft (A), followed by bovine bone xenograft (B) and connective tissue graft (C). Autogenous bone is placed in contact with the implant surface to induce osseointegration; bovine bone xenograft is then applied to augment the ridge dimension and provide long-term stability. Connective tissue is used to provide additional volume. The ABC biomaterial sequence offers favorable hard and soft tissue dimensions and immediate provisional restoration predictably leads to an esthetically pleasing definitive prosthesis. PMID- 26133147 TI - Surgical Techniques to Increase the Apicocoronal Dimension of the Attached Gingiva: A 1-Year Comparison Between the Free Gingival Graft and the Modified Apically Repositioned Flap. AB - The attached gingiva is a desirable anatomical element for the maintenance of gingival health. The free gingival graft (FGG) and the modified apically repositioned flap (MARF) are predictable surgical techniques often employed to increase the zone of attached gingiva. This randomized study compared the FGG and the MARF in increasing the zone of attached gingiva in contralateral sides of 15 patients 1 year posttreatment. There was an increase in keratinized tissue and attached gingiva in both groups. Gingival recession did not significantly change between pre- and posttreatment levels in either group. The MARF surgical time was approximately half as long as that of the FGG. The authors conclude that both techniques are viable; however, the main advantages of the MARF were decreased surgical time and less postoperative discomfort. PMID- 26133148 TI - Influence of Conventional and Digital Wax-ups on Axial Tooth Contour. AB - The aim of this study was to evaluate the impact of conventional and digital diagnostic wax-up on the axial tooth contour. Dental models of 15 patients were collected. Each model received conventional wax-up and digital wax-up. The conventional wax-up was based on tooth modification with dental wax on actual models. The digital wax-up involved fitting an average tooth form on virtual pretreatment models. Each wax-up model was digitally superimposed on the corresponding pretreatment model. For each modified tooth, analysis planes were extracted at three locations: mesial line angle, midtooth, and distal line angle. The impact of the following variables was evaluated: interarch location (maxilla vs mandible), intra-arch location (anterior vs posterior), tooth category (incisors, canines, premolars, and molars), and tooth location (midtooth vs line angle). The axial contour of the modified teeth increased after each wax-up, and this increase was directly proportional to the distance from the gingival margin. There is a clear tendency for the digital wax-up to cause a greater contour increase than the conventional wax-up. The anterior teeth were associated with a greater tooth contour increase than posterior teeth and the contour of the molars was the least affected. Although the conventional wax-up contour alteration was significantly less than for the digital wax-up, the actual difference was minimal. PMID- 26133149 TI - Location of Posterosuperior Alveolar Artery and Correlation with Maxillary Sinus Anatomy. AB - The blood supply to both the lateral wall of the maxillary sinus and the overlying membrane originates from the posterosuperior alveolar artery (PSAA) and the infraorbital artery. The purpose of the present study was to evaluate the anatomic characteristics of the PSAA in a large number of subjects of the Lebanese population. Images of 696 sinuses were analyzed using cone beam computed tomography (CT). Coronal, axial, and sagittal CT images were evaluated for the presence of an osseous canal in the lateral wall of the sinus, and the prevalence, position, and location of the canal were studied and presented. PMID- 26133150 TI - Consecutive Case Series Using a Composite Allograft Containing Mesenchymal Cells with an Amnion-Chorion Barrier to Treat Mandibular Class III/IV Furcations. AB - This retrospective case series describes a layered regenerative approach for five Class III and one borderline Class IV furcation, involving treatment consisting of root management that included conditioning with tetracycline solution followed by the topical application of recombinant platelet-derived growth factor BB. A composite allograft with mesenchymal stem cells was subsequently placed into the furcation and covered by a barrier derived from human amnion-chorion with flaps advanced to completely cover the site. Three furcations, including the one diagnosed as Class IV, had complete closure, two were converted to Class I, and in one instance, there was no improvement. This regenerative algorithm for mandibular Class III furcations may present the potential to save these teeth by altering the prognosis, which has traditionally been poor to hopeless, resulting in many of these teeth routinely being extracted. PMID- 26133151 TI - Review of Neoadjuvant Chemotherapy Alone in Locally Advanced Rectal Cancer. AB - BACKGROUND: Currently, the standard management of locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy followed by resection. Despite the significant improvement in local recurrence, survival benefits are not gained due to distant failure and radiotherapy-associated toxicity. Compliance to adjuvant chemotherapy after preoperative chemoradiotherapy is also poor. Neoadjuvant chemotherapy alone followed by surgery may be an alternative. The objective of this review is to determine the efficacy of neoadjuvant chemotherapy alone in operable LARC. MATERIALS AND METHODS: Electronic databases searched (from database inception-December 2013) were Medline, PubMed, Embase, Scopus, Cochrane library, and the Clinical Trials Register. Specific journals were also hand searched. The selection criteria were studies published in English investigating stage II-III non-metastatic rectal cancer patients treated with neoadjuvant chemotherapy (oral, intravenous or rectal route) followed by curative resection. The primary outcome measure was tumour response. Secondary outcome measures included acute toxicity, operative morbidity, R0 resection, local recurrence, overall survival (OS) and disease-free survival (DFS). RESULTS: One randomised phase III trial, six single-arm phase II trials and one retrospective case series study were eligible for inclusion. Six studies administered fluoropyrimidine based multiple agent regimens and two studies administered fluorouracil-based monotherapy. The studies with multiple agents and stronger chemotherapy regimens (intravenous and/or oral) followed by delayed surgery showed better tumour response rates. The overall objective response rate was good and ranged from 62.5 to 93.7 %. Pathological complete response ranged from 3.8 to 33.3 %. The R0 resection and compliance rates were also high ranging from 90 to 100 % and 72 to 100 %, respectively. Grade 3-4 toxicities ranged from 2.3 to 39 %. Four- to 5 year OS and DFS ranged from 67.2 to 91 % and 60.5 to 84 %, respectively. CONCLUSION: This review demonstrates that neoadjuvant chemotherapy could be affectively administered in LARC and could provide a good alternative to chemoradiotherapy in moderate-risk rectal cancers without compromising short- and long-term outcomes. PMID- 26133152 TI - The New Zealand experience of varroa invasion highlights research opportunities for Australia. AB - The Varroa mite (Varroa destructor) is implicated as a major disease factor in honey bee (Apis mellifera) populations worldwide. Honey bees are extensively relied upon for pollination services, and in countries such as New Zealand and Australia where honey bees have been introduced specifically for commercial pollinator services, the economic effects of any decline in honey bee numbers are predicted to be profound. V. destructor established in New Zealand in 2000 but as yet, Australia remains Varroa-free. Here we analyze the history of V. destructor invasion and spread in New Zealand and discuss the likely long-term impacts. When the mite was discovered in New Zealand, it was considered too well established for eradication to be feasible. Despite control efforts, V. destructor has since spread throughout the country. Today, assessing the impacts of the arrival of V. destructor in this country is compromised by a paucity of data on pollinator communities as they existed prior to invasion. Australia's Varroa-free status provides a rare and likely brief window of opportunity for the global bee research community to gain understanding of honey bee-native pollinator community dynamics prior to Varroa invasion. PMID- 26133153 TI - EMBO workshop al fin del mundo: a meeting on membrane trafficking and its implication for polarity and diseases. AB - The EMBO worskhop at the "end of the world'" (al fin del mundo), a meeting on membrane trafficking and its implication for polarity and diseases, took place in the Chilean Patagonia surrounded by the landscapes once witnessed by Charles Darwin. The meeting showcased some of the best membrane trafficking science with an emphasis in neuroscience and disease models. Speakers from Europe, USA, South America and the graduate students behind it; embarked on an enthusiastic and eclectic dialog where a wide range of cell types, model genetic systems, and diseases where discussed. This meeting demonstrated the power of trafficking concepts to integrate diverse biology and to formulate mechanisms of normal and disease cells. PMID- 26133154 TI - Erratum. PMID- 26133157 TI - Atrial fibrillation and hypertrophic cardiomyopathy: who to anticoagulate? AB - Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac conditions. Atrial fibrillation (AF) has been demonstrated to be the most frequent arrhythmia encountered in HCM patients. Research focusing on AF and embolic stroke in HCM patients has been sparse and the sample size of most studies is small. The prognostic significance of AF in HCM patients is still not well known. The aim of this article is to provide further understanding of the anti-coagulation requirement of HCM patients with AF. PMID- 26133159 TI - Pentagonal helices in a periodic metal-organic framework. Crystals as computers for discovering structures of minimal transitivity. AB - The structure of a recently-published metal-organic framework is deconstructed into its underlying net which is found to be of exceptional complexity. It is shown that this is because of local pentagonal symmetry and the structure is in fact the simplest possible (minimal transitivity) given that local symmetry. PMID- 26133158 TI - Predictors of outcome in patients with parvovirus B19 positive endomyocardial biopsy. AB - OBJECTIVE: Primary objective was to establish the prognostic value of the myocardial load of PVB19 genomes in patients presenting for work-up of myocarditis and/or unclear cardiomyopathy in comparison to clinical, and CMR parameters. METHODS: 108 consecutive patients who underwent EMB because of suspected myocarditis and/or unclear cardiomyopathy, and had evidence of myocardial PVB19 genome, were enrolled. Primary endpoint was all-cause mortality; secondary endpoint was a composite of cardiac mortality and hospitalization for heart failure. RESULTS: Mean LV-EF was 40%. We found n = 27 patients to have a viral load >= 500 GE (IQR 559-846), n = 72 had 100-499 GE, and n = 9 had <100 GE. Immunohistology revealed chronic myocarditis in n = 66, acute myocarditis in n = 1, DCM in n = 17, PVB19 genome only in n = 13, and other pathologies in n = 11. During follow-up 11 patients died, two suffered SCD but were successfully shocked by ICD, and 21 were hospitalized for heart failure. Interestingly, not the viral load, but functional parameters such as LV-EF, LV-EDV (endpoint 2), as well as the histologic diagnosis of DCM and the presence of LGE (for all endpoints) reached statistical significance. In fact, the presence of LGE yields an odds ratio for a lethal event of 8.56 (endpoint 1), and of 5.52 for endpoint 2. No patient with normal LV-EF, or the absence of LGE, suffered cardiac death during long-term follow-up. CONCLUSION: The viral load of PVB19 genomes in the myocardium is not related to the long-term outcome. Furthermore, this study suggests a growing role of imaging for risk stratification in non-ischemic myocardial disease. PMID- 26133160 TI - Whole Grain Consumption Increases Gastrointestinal Content of Sulfate-Conjugated Oxylipins in Pigs - A Multicompartmental Metabolomics Study. AB - The effects of increased intake of dietary fiber as either whole grain rye or as resistant starch compared to a typical low dietary fiber Western-style diet on the metabolomics responses were studied in gastrointestinal content and tissue, peripheral plasma, and urine using a multicompartmental nontargeted liquid chromatography-mass spectrometry (LC-MS) approach in pigs. Both unsupervised and supervised multivariate analyses were used to study differences between the intervention groups, revealing significant effects of the dietary intervention on gastrointestinal contents and urine metabolites. Consumption of a diet composed of whole grain rye flakes and enzyme treated wheat bran increased gastrointestinal content of novel sulfate- and acetic acid-conjugated oxylipins, and urinary secretion of phenolic compounds. Furthermore, potential gastrointestinal and urinary biomarkers for consumption of resistant starch, whole grain rye, and a low dietary fiber intake were detected using multiblock analysis. This study provides insight into microbial fermentation products in the gastrointestinal tract and suggests a potential role in sulfate conjugation of metabolites on the bioavailability of ingested nutrients. PMID- 26133161 TI - [Health literacy in childhood and adolescence: An overview and current state of research]. AB - BACKGROUND: Health literacy is multidisciplinary and brings together many concepts, and is of increasing importance for disease protection, health promotion, and prevention, and for health policy within Europe. Although its importance is increasingly recognised, adults are mostly the target audience, whereas children and adolescents, in addition to education and schools, have so far been neglected. OBJECTIVES: The aim is to give an overview of the state of the art in childhood and adolescence health literacy research, and to identify any existing gaps. MATERIALS: A literature review has been performed to identify the relevant research data. RESULTS: Limitations in developmental and age adjusted conceptual frameworks and a lack of prevalence data, however, significantly impede our understanding of the meaning of health literacy in children and adolescents. School health promotion programmes could serve as a platform for effective health literacy education, beginning in early childhood. CONCLUSIONS: In addition to compatibility with a broader literacy perspective, the proximity to several theories of health promotion and defined concepts, and the importance of school health promotion and education, it is vital to focus research on current gaps in the understanding of health literacy determinants, health literacy as a determinant of health, and in terms of the design and systematic implementation of intervention programmes. PMID- 26133162 TI - [Occupational gratification crisis and sickness absence in Germany: Cross sectional results from the lidA-study]. AB - BACKGROUND: Demographic change is leading to a shrinking and ageing workforce in industrialized nations. Therefore, sickness absence may become a relevant problem. Increasing absenteeism and retirement rates due to mental disorders raise the question of an association between work-related stress and sickness absence. Studies on this matter, particularly in older employees, are rare. OBJECTIVES: We studied for the first time in Germany the relationship between effort-reward imbalance (ERI) and overall or long-term sickness absence. MATERIALS AND METHODS: LidA ( "Living at Work") is a German cohort study on work, age, health, and work participation. A total of 6,339 employees born in 1959 and 1965 who were subject to social insurance contributions were interviewed nationwide using a representative sample concept. The response rate was 27.3 %. The sample showed high representativeness and no selectivity relating to 16 sociodemographic items. Sickness absence was defined as at least one long-term sickness absence with at least 43 days of absenteeism. Work-related stress was parameterized by ERI tertiles. Multiple logistic regression adjusting for age, sex, mental disorders, social status, and working time was performed. RESULTS: High levels of work-related stress were significantly associated with overall and long-term sickness absence among older employees after adjusting for covariates. CONCLUSIONS: Our unique findings on work-related stress and sickness absence in Germany are in agreement with the results of most international studies. Reducing work-related stress could help to preserve the workforce. PMID- 26133163 TI - Dopamine transporter imaging in essential tremor with and without parkinsonian features. AB - Mild parkinsonian features can be observed in patients with essential tremor (ET). Although dopamine transporter (DAT) imaging is usually normal in ET, some studies found mild dopaminergic deficit in ET patients compared to healthy controls (HC). We analyzed clinical and DAT imaging data in ET patients with and without parkinsonian features. Thirty-nine ET patients with and without parkinsonian features and 13 HC underwent detailed examination by a movement disorders neurologist and 123-I ioflupane SPECT. Two independent radiologists "blinded" to the clinical diagnosis analyzed images visually and by semi quantitative calculation of striatal binding ratios in different volumes of interests. ET patients were divided into pure ET group (no parkinsonian features, n = 22), ET-P [one parkinsonian feature not sufficient for the clinical diagnosis of Parkinson's disease (PD), n = 9], and ET + PD (two or more parkinsonian features meeting diagnostic criteria for PD, n = 8). As expected, ET + PD patients had the lowest striatal binding ratios. We also found a trend toward slightly lower striatal binding ratios in ET patients ET compared to HC, especially in caudate nucleus. There was no significant correlation between striatal binding ratios, ET severity or duration. Patients with ET and parkinsonian features represent a heterogeneous group that includes ET + PD and ET-P. The latter group shares some clinical features with PD but has no dopaminergic deficit on DAT imaging as determined by visual image interpretation. On the other hand, minimal dopaminergic deficit (as compared to controls) is detected in some ET patients with semi-quantitative image analysis, although the pattern may be different from that of PD. PMID- 26133164 TI - The triplet puzzle theory indicates extensive formation of heteromers between opioid and chemokine receptor subtypes. AB - Biochemical studies had previously demonstrated examples of heteromerization between opioid and chemokine receptors. Based on the triplet puzzle theory, it has been discovered that opioid receptors are structurally more closely related to chemokine receptors than to other class A G-protein-coupled receptors. Their similarity is established in terms of the number of triplet homologies Asn-Leu Ala, Thr-Leu-Pro, and Tyr-Ala-Phe in the amino acid code of extensive numbers of members of these two receptor groups. Such widespread similarities probably mean that many opioid and chemokine receptor subtypes utilize some of these mutual triplets to form heteromers. The findings underline that heteromerization among these two receptor groups can represent a major general mechanism for significant interactions between opioid peptides and chemokines in pain and neuroinflammation within the neural-glial networks of the CNS including immune cells. PMID- 26133165 TI - Antimicrobial Susceptibility Patterns in Urinary Tract Infections in Dogs (2010 2013). AB - BACKGROUND: Urinary tract infections (UTIs) are common in dogs. The responsible bacterial populations have evolved with increasing resistance to many antimicrobials. OBJECTIVE: To characterize the antimicrobial susceptibility patterns of canine urinary tract isolates over a 51-month period. ANIMALS: One thousand six hundred and thirty-six bacterial isolates from 1,028 dogs. METHODS: Aerobic bacterial isolate growth and susceptibility data from urine cultures of dogs were identified, retrospectively. Medical records were reviewed to obtain signalment, comorbidities, and antimicrobial use in the previous 30 days. The UTIs were further categorized as uncomplicated, complicated, or pyelonephritis. RESULTS: Common bacterial isolates identified were Escherichia coli (52.5%), Staphylococcus spp. (13.6%), and Enterococcus spp. (13.3%). In vitro susceptibility among all isolates varied for commonly prescribed antimicrobials (amoxicillin [59%], amoxicillin/clavulanic acid [76%], cephalexin [66%], enrofloxacin [74%] and trimethoprim-sulfamethoxazole [86%]). For all antimicrobials tested (except aminoglycosides), in vitro susceptibility was higher in uncomplicated versus complicated infections (P < .05). Uncomplicated infection isolate susceptibility rates remained <=90% for PO administered antimicrobials. Administration of amoxicillin, doxycycline, and enrofloxacin, but not amoxicillin/clavulanic acid in the previous 30 days was associated with resistance to that antimicrobial. Multidrug resistant isolates of E. coli and Staphylococcus spp. were more common in dogs with complicated than uncomplicated UTIs (36% versus 21%, P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: In vitro susceptibility was highly variable and no PO administered antimicrobial had >90% efficacy among isolates tested. Multidrug resistance was frequent among isolates tested suggesting that routine culture and susceptibility testing is indicated. Previously prescribed antimicrobials may affect empirical choices made pending susceptibility testing. PMID- 26133166 TI - Assessment of arterial stiffness using pulse wave velocity in tacrolimus users the first year post kidney transplantation: a prospective cohort study. AB - BACKGROUND: The leading cause of death in end stage renal disease is cardiovascular disease (CVD). Kidney transplantation is associated with improved survival over dialysis. We hypothesized that arterial stiffness, a marker of CVD, would improve in patients post kidney transplant, potentially explaining one mechanism of survival benefit from transplant. METHODS: After obtaining Institutional Review Board approval and informed consent, we performed a longitudinal prospective cohort study of 66 newly transplanted adult kidney transplant recipients, using aortic pulse wave velocity (PWV) to assess arterial stiffness over a 12 month period. All patients were assessed within one month of transplant (baseline) and 12 months post transplant. The primary outcome was change in PWV score at 12 months which we assessed using Wilcoxon Signed Rank test. Secondary analyses included correlation of predictors with PWV score at both time points. RESULTS: The median age of the cohort was 49.7 years at transplant, with 27 % Black and 27 % female. At baseline, 43 % had tobacco use, 30 % had a history of CVD, and 42 % had diabetes. Median baseline calcium was 9.1 mg/dL and median phosphorus was 5.1 mg/dL. Median PWV score was 9.25 and 8.97 m/s at baseline versus month 12, respectively, showing no significant change (median change of -0.07, p = 0.7). In multivariable regression, subjects with increased age at transplant (p = 0.008), diabetes (p = 0.002), and a higher baseline PWV score (p < 0.001) were at increased risk of having a high PWV score 12 months post transplant. CONCLUSION: Aortic arterial stiffness does not progress in the first year post kidney transplant. Increasing age, diabetes, and higher baseline PWV score identify patients at risk for increased arterial stiffness. Further research that assesses patients for greater than one year and includes a control dialysis group would be helpful in further understanding the change in arterial stiffness post transplantation. PMID- 26133168 TI - Cell Free DNA of Tumor Origin Induces a 'Metastatic' Expression Profile in HT-29 Cancer Cell Line. AB - BACKGROUND: Epithelial cells in malignant conditions release DNA into the extracellular compartment. Cell free DNA of tumor origin may act as a ligand of DNA sensing mechanisms and mediate changes in epithelial-stromal interactions. AIMS: To evaluate and compare the potential autocrine and paracrine regulatory effect of normal and malignant epithelial cell-related DNA on TLR9 and STING mediated pathways in HT-29 human colorectal adenocarcinoma cells and normal fibroblasts. MATERIALS AND METHODS: DNA isolated from normal and tumorous colonic epithelia of fresh frozen surgically removed tissue samples was used for 24 and 6 hour treatment of HT-29 colon carcinoma and HDF-alpha fibroblast cells. Whole genome mRNA expression analysis and qRT-PCR was performed for the elements/members of TLR9 signaling pathway. Immunocytochemistry was performed for epithelial markers (i.e. CK20 and E-cadherin), DNA methyltransferase 3a (DNMT3a) and NFkappaB (for treated HDFalpha cells). RESULTS: Administration of tumor derived DNA on HT29 cells resulted in significant (p<0.05) mRNA level alteration in 118 genes (logFc>=1, p<=0.05), including overexpression of metallothionein genes (i.e. MT1H, MT1X, MT1P2, MT2A), metastasis-associated genes (i.e. TACSTD2, MACC1, MALAT1), tumor biomarker (CEACAM5), metabolic genes (i.e. INSIG1, LIPG), messenger molecule genes (i.e. DAPP, CREB3L2). Increased protein levels of CK20, E-cadherin, and DNMT3a was observed after tumor DNA treatment in HT-29 cells. Healthy DNA treatment affected mRNA expression of 613 genes (logFc>=1, p<=0.05), including increased expression of key adaptor molecules of TLR9 pathway (e.g. MYD88, IRAK2, NFkappaB, IL8, IL-1beta), STING pathway (ADAR, IRF7, CXCL10, CASP1) and the FGF2 gene. CONCLUSIONS: DNA from tumorous colon epithelium, but not from the normal epithelial cells acts as a pro-metastatic factor to HT-29 cells through the overexpression of pro-metastatic genes through TLR9/MYD88 independent pathway. In contrast, DNA derived from healthy colonic epithelium induced TLR9 and STING signaling pathway in normal fibroblasts. PMID- 26133167 TI - Activation of Phosphatidylinositol-Linked Dopamine Receptors Induces a Facilitation of Glutamate-Mediated Synaptic Transmission in the Lateral Entorhinal Cortex. AB - The lateral entorhinal cortex receives strong inputs from midbrain dopamine neurons that can modulate its sensory and mnemonic function. We have previously demonstrated that 1 uM dopamine facilitates synaptic transmission in layer II entorhinal cortex cells via activation of D1-like receptors, increased cAMP-PKA activity, and a resulting enhancement of AMPA-receptor mediated currents. The present study assessed the contribution of phosphatidylinositol (PI)-linked D1 receptors to the dopaminergic facilitation of transmission in layer II of the rat entorhinal cortex, and the involvement of phospholipase C activity and release of calcium from internal stores. Whole-cell patch-clamp recordings of glutamate mediated evoked excitatory postsynaptic currents were obtained from pyramidal and fan cells. Activation of D1-like receptors using SKF38393, SKF83959, or 1 uM dopamine induced a reversible facilitation of EPSCs which was abolished by loading cells with either the phospholipase C inhibitor U-73122 or the Ca2+ chelator BAPTA. Neither the L-type voltage-gated Ca2+ channel blocker nifedipine, nor the L/N-type channel blocker cilnidipine, blocked the facilitation of synaptic currents. However, the facilitation was blocked by blocking Ca2+ release from internal stores via inositol 1,4,5-trisphosphate (InsP3) receptors or ryanodine receptors. Follow-up studies demonstrated that inhibiting CaMKII activity with KN-93 failed to block the facilitation, but that application of the protein kinase C inhibitor PKC(19-36) completely blocked the dopamine-induced facilitation. Overall, in addition to our previous report indicating a role for the cAMP-PKA pathway in dopamine-induced facilitation of synaptic transmission, we demonstrate here that the dopaminergic facilitation of synaptic responses in layer II entorhinal neurons also relies on a signaling cascade dependent on PI linked D1 receptors, PLC, release of Ca2+ from internal stores, and PKC activation which is likely dependent upon both DAG and enhanced intracellular Ca2+. These signaling pathways may collaborate to enhance sensory and mnemonic function in the entorhinal cortex during tonic release of dopamine. PMID- 26133169 TI - Comparative Transcriptome Analysis of Shoots and Roots of TNG67 and TCN1 Rice Seedlings under Cold Stress and Following Subsequent Recovery: Insights into Metabolic Pathways, Phytohormones, and Transcription Factors. AB - Cold stress affects rice growth, quality and yield. The investigation of genome wide gene expression is important for understanding cold stress tolerance in rice. We performed comparative transcriptome analysis of the shoots and roots of 2 rice seedlings (TNG67, cold-tolerant; and TCN1, cold-sensitive) in response to low temperatures and restoration of normal temperatures following cold exposure. TNG67 tolerated cold stress via rapid alterations in gene expression and the re establishment of homeostasis, whereas the opposite was observed in TCN1, especially after subsequent recovery. Gene ontology and pathway analyses revealed that cold stress substantially regulated the expression of genes involved in protein metabolism, modification, translation, stress responses, and cell death. TNG67 takes advantage of energy-saving and recycling resources to more efficiently synthesize metabolites compared with TCN1 during adjustment to cold stress. During recovery, expression of OsRR4 type-A response regulators was upregulated in TNG67 shoots, whereas that of genes involved in oxidative stress, chemical stimuli and carbohydrate metabolic processes was downregulated in TCN1. Expression of genes related to protein metabolism, modification, folding and defense responses was upregulated in TNG67 but not in TCN1 roots. In addition, abscisic acid (ABA)-, polyamine-, auxin- and jasmonic acid (JA)-related genes were preferentially regulated in TNG67 shoots and roots and were closely associated with cold stress tolerance. The TFs AP2/ERF were predominantly expressed in the shoots and roots of both TNG67 and TCN1. The TNG67-preferred TFs which express in shoot or root, such as OsIAA23, SNAC2, OsWRKY1v2, 24, 53, 71, HMGB, OsbHLH and OsMyb, may be good candidates for cold stress tolerance-related genes in rice. Our findings highlight important alterations in the expression of cold-tolerant genes, metabolic pathways, and hormone-related and TF-encoding genes in TNG67 rice during cold stress and recovery. The cross-talk of hormones may play an essential role in the ability of rice plants to cope with cold stress. PMID- 26133170 TI - Increased CCL2, CCL3, CCL5, and IL-1beta cytokine concentration in piriform cortex, hippocampus, and neocortex after pilocarpine-induced seizures. AB - BACKGROUND: Cytokines and chemokines play an important role in the neuroinflammatory response to an initial precipitating injury such as status epilepticus (SE). These signaling molecules participate in recruitment of immune cells, including brain macrophages (microglia), as well as neuroplastic changes, deterioration of damaged tissue, and epileptogenesis. This study describes the temporal and brain region pattern expression of numerous cytokines, including chemokines, after pilocarpine-induced seizures and discusses them in the larger context of their potential involvement in the changes that precede the development of epilepsy. FINDINGS: Adult rats received pilocarpine to induce SE and 90 min after seizure onset were treated with diazepam to mitigate seizures. Rats were subsequently deeply anesthetized and brain regions (hippocampus, piriform cortex, neocortex, and cerebellum) were freshly dissected at 2, 6, and 24 h or 5 days after seizures. Using methodology identical to our previous studies, simultaneous assay of multiple cytokines (CCL2, CCL3, CCL5, interleukin IL-1beta, tumor necrosis factor (TNF-alpha)), and vascular endothelial growth factor (VEGF) was performed and compared to control rats. These proteins were selected based on existing evidence implicating them in the epileptogenic progression. A robust increase in CCL2 and CCL3 concentrations in the hippocampus, piriform cortex, and neocortex was observed at all time-points. The concentrations peaked with a ~200-fold increase 24 h after seizures and were two orders of magnitude greater than the significant increases observed for CCL5 and IL-1beta in the same brain structures. TNF-alpha levels were altered in the piriform cortex and neocortex (24 h) and in the hippocampus (5 days) after SE. CONCLUSIONS: Pilocarpine-induced status epilepticus causes a rapid increase of multiple cytokines in limbic and neocortical regions. Understanding the precise spatial and temporal pattern of cytokines and chemokine changes could provide more viable therapeutic targets to reduce, reverse, or prevent the development of epilepsy following a precipitating injury. PMID- 26133171 TI - Mosquitoes Reset Malaria Parasites. PMID- 26133172 TI - Platelet functional alterations in a Bernard-Soulier syndrome patient with filamin A mutation. AB - Defects in filamin A (FLNA) gene could lead to low platelet counts and decreased surface expression of glycoprotein (GP) Ibalpha. Here, we report and investigate the FLNA genomic alteration of a case with Bernard-Soulier syndrome (BSS), a rare hereditary bleeding disorder caused by quantitative or qualitative abnormalities in the GP Ib-IX-V receptor. DNA sequencing analysis reveals the presence of a GP Ibalpha c.987G > A mutation and a FLNA c.1582 G > A mutation in this patient. Transient transfection studies show that GP Ibalpha c.987G > A mutation abolishes the surface expression of GP Ibalpha on the transfected CHO cells. On the other hand, abnormal responses to collagen, including the platelet aggregation, secretion, and GP VI signaling pathways, are associated with FLNA c.1582G > A mutation. Our findings confirm a central role for FLNA in platelet-adhesive functions. The interaction between FLNA and GP Ibalpha in platelets deserves to be investigated. PMID- 26133173 TI - Screening for Suitable Reference Genes for Quantitative Real-Time PCR in Heterosigma akashiwo (Raphidophyceae). AB - The raphidophyte Heterosigma akashiwo is a globally distributed harmful alga that has been associated with fish kills in coastal waters. To understand the mechanisms of H. akashiwo bloom formation, gene expression analysis is often required. To accurately characterize the expression levels of a gene of interest, proper reference genes are essential. In this study, we assessed ten of the previously reported algal candidate genes (rpL17-2, rpL23, cox2, cal, tua, tub, ef1, 18S, gapdh, and mdh) for their suitability as reference genes in this species. We used qRT-PCR to quantify the expression levels of these genes in H. akashiwo grown under different temperatures, light intensities, nutrient concentrations, and time points over a diel cycle. The expression stability of these genes was evaluated using geNorm and NormFinder algorithms. Although none of these genes exhibited invariable expression levels, cal, tub, rpL17-2 and rpL23 expression levels were the most stable across the different conditions tested. For further validation, these selected genes were used to normalize the expression levels of ribulose-1, 5-bisphosphate carboxylase/oxygenase large unite (HrbcL) over a diel cycle. Results showed that the expression of HrbcL normalized against each of these reference genes was the highest at midday and lowest at midnight, similar to the diel patterns typically documented for this gene in algae. While the validated reference genes will be useful for future gene expression studies on H. akashiwo, we expect that the procedure used in this study may be helpful to future efforts to screen reference genes for other algae. PMID- 26133174 TI - Pregnancy wastage among HIV infected women in a high HIV prevalence district of India. AB - BACKGROUND: Bagalkot district in Karnataka state is one of the highest HIV prevalence districts in India. A large proportion of the girls also marry at early age in the district and negative pregnancy outcomes among the HIV positive women likely to have large pregnancy wastages. Therefore, this study examined the pregnancy wastages and the associated factors among HIV positive women in a high prevalent district in India. METHODS: We used data from a cross-sectional survey conducted recently among randomly selected currently married HIV positive women, 15-29 years of age, in one of the high HIV prevalence districts in India. The study used the experience of reported pregnancy wastage as an outcome variable, and both bi-variate and multivariate logistic regression analyses were carried out to understand the factors associated with the pregnancy wastage among HIV infected women. RESULTS: Overall, 17% of the respondents reported pregnancy wastage, of which 81% were due to spontaneous abortions. Respondents who became pregnant since testing HIV positive reported significantly higher level of pregnancy wastage as compared to those were pregnant before they were tested for HIV. (AOR = 1.9; p = 0.00). While a positive association between duration of marriage and pregnancy wastage was noticed (AOR = 7.4; p = 0.01), there was a negative association between number of living children and pregnancy wastage (AOR = 0.24; p = 0.00). Living in a joint family was associated with increased reporting of pregnancy wastage as compared to those living in nuclear families (AOR = 1.7; p = 0.03). CONCLUSIONS: HIV prevention and care programs need to consider the reproductive health needs of HIV infected married women as a priority area since large proportion of these women reported negative pregnancy outcomes. There is also a need to explore ways to raise the age at marriage in order to stop women getting married before the legal age at marriage. PMID- 26133175 TI - Computer vision and augmented reality in gastrointestinal endoscopy. AB - Augmented reality (AR) is an environment-enhancing technology, widely applied in the computer sciences, which has only recently begun to permeate the medical field. Gastrointestinal endoscopy-which relies on the integration of high definition video data with pathologic correlates-requires endoscopists to assimilate and process a tremendous amount of data in real time. We believe that AR is well positioned to provide computer-guided assistance with a wide variety of endoscopic applications, beginning with polyp detection. In this article, we review the principles of AR, describe its potential integration into an endoscopy set-up, and envisage a series of novel uses. With close collaboration between physicians and computer scientists, AR promises to contribute significant improvements to the field of endoscopy. PMID- 26133177 TI - Exercise in Youth with Type 1 Diabetes. AB - Exercise is important in the management of type 1 diabetes mellitus (T1DM). Modern diabetes care includes the goal that all youth meet guidelines for regular physical activity. Evidence suggests regular physical activity improves cardiovascular health, lipid profiles, psychosocial wellbeing and, possibly, glycemic control in youth with T1DM. However, exercise is especially problematic for children and adolescents because wide glycemic excursions commonly occur during and after exercise and may increase the risk of severe hypoglycemia. In addition, youth with T1DM have abnormal counterregulatory hormone responses, further increasing the risk of exercise-associated hypoglycemia. Recent studies have demonstrated that this risk is present during, and many hours after exercise, and have tested strategies to prevent exercise-induced hypoglycemia in youth. Despite these recent studies, the fear of hypoglycemia remains a major impediment to achieving target glycemic control in youth, targets that have recently been tightened. Equally, data suggests fear of hypoglycemia is the major impediment to participation in regular daily exercise in T1DM. Recent advances in insulin delivery systems and in real time continuous glucose monitoring have improved care for youth with T1DM, allowing safer participation in exercise programs. The impending development and approval of "closed loop" insulin delivery systems (the artificial pancreas) holds great promise for the safe participation in exercise for all youth with T1DM. PMID- 26133176 TI - Monitoring of Water Spectral Pattern Reveals Differences in Probiotics Growth When Used for Rapid Bacteria Selection. AB - Development of efficient screening method coupled with cell functionality evaluation is highly needed in contemporary microbiology. The presented novel concept and fast non-destructive method brings in to play the water spectral pattern of the solution as a molecular fingerprint of the cell culture system. To elucidate the concept, NIR spectroscopy with Aquaphotomics were applied to monitor the growth of sixteen Lactobacillus bulgaricus one Lactobacillus pentosus and one Lactobacillus gasseri bacteria strains. Their growth rate, maximal optical density, low pH and bile tolerances were measured and further used as a reference data for analysis of the simultaneously acquired spectral data. The acquired spectral data in the region of 1100-1850nm was subjected to various multivariate data analyses - PCA, OPLS-DA, PLSR. The results showed high accuracy of bacteria strains classification according to their probiotic strength. Most informative spectral fingerprints covered the first overtone of water, emphasizing the relation of water molecular system to cell functionality. PMID- 26133178 TI - Role of Fibroblast Growth Factor 21 (FGF21) in the Regulation of Statural Growth. AB - In this review, we discuss the evidence supporting the causative role of increased FGF21 expression in reduced GH action and impaired longitudinal bone growth. Fibroblast Growth Factor (FGF) 21 (FGF21) is a member of a subfamily of FGFs which lack the FGF heparin-binding domain. Thus, these FGFs can function as endocrine as well as paracrine factors. During fasting, increased expression of FGF21 induces gluconeogenesis, fatty acid oxidation, and ketogenesis: as a result, FGF21 is considered a key regulator of the metabolic adaptation to fasting. In addition, recent evidence indicates that FGF21 may regulate longitudinal bone growth. It has been shown that transgenic mice overexpressing FGF21 exhibit reduced bone growth and hepatic Growth Hormone (GH) insensitivity. FGF21 knock-out mice exposed to chronic food restriction experience greater body and tibial growth than their food-restricted wild-type littermates, suggesting that the increased FGF21 expression in wild-type mice during undernutrition leads to reduced skeletal growth. The FGF21-mediated attenuation of bone growth appears to be secondary to reduced GH sensitivity, both systemically and locally in the long bones' growth plate. The effects of FGF21 on GH action are direct, and may result from the reduced translocation of GH receptors from the cytoplasm to the cell membrane. Lastly, we discuss recent studies which have shown that FGF21 in infancy is inversely correlated with linear growth rate. In conclusion, all the evidence discussed in this review indicates that FGF21 may be an important negative regulator of mammalian growth. PMID- 26133179 TI - A Pilot Study to Assess the Vestibular Apparatus Function with Videonystagmography During Chronic Otitis Media with Effusion. AB - OBJECTIVE: To assess the effect of chronic middle ear effusion (CMEE) on balance and equilibrium. MATERIAL AND METHODS: Prospective study controlling two groups of children. The active arm consisted of children having a unilateral or bilateral CMEE that persisted for at least 3 months. The control group consisted of children presenting with normal middle ear. Children and parents in both groups were questioned about any symptom of vertigo, dizziness, disequilibrium or child's tendency to fall. ENT exam included an assessment with pneumatic and microscopic otoscopy, evaluation of the vestibular system with the Romberg test, the Fukuda test, the head-shaking test and the Starwalk test. RESULTS: The study group consisted of 15 children (mean = 6.5 years, SD = 2; 10 females and 5 males). The control group consisted also of 15 children (mean = 7.2 years, SD = 1.8; 8 females and 7 males). The duration of MEE was between 3 and 12 months (mean = 8 months). Three children (20%) in the study group had a history of vertigo, imbalance, disequilibrium and/or tendency to fall. None of the children in the control group had such a history (p = 0.22); Five children in the study group had abnormal head-shaking test, Fukuda and/or Starwalk tests (33.33%). Two children in the control group had such a finding (13.33%) (p = 0.39). Romberg test was normal in all children in both groups. In the study group, one child showed positional and spontaneous nystagmus on VNG testing. Another one showed positional nystagmus. Hence, 2 children had abnormal findings on VNG (13.33%). In the control group, VNG was normal in all children (p = 0.46). Tympanometry showed a type B curve in 26 ears, a type C curve in 3 ears and type A in one ear. In the control group all patients presented a type A curve. CONCLUSION: This paper describes the first study using VNG in a population of children with CMEE. The presence of balance disturbances associated or not with hearing loss is of paramount importance to the clinician as to the indications of myringotomy with a tube intervention. PMID- 26133180 TI - Non-transfusion Dependent Thalassemias: A Developing Country Perspective. AB - Non-transfusion-dependent thalassemias (NTDT) encompass a group of hereditary chronic hemolytic anemia, which, as the name indicates, not require regular blood transfusion for survival. These include beta-thalassemia intermedia, hemoglobin E/beta-thalassemia, and Hemoglobin H disease (alpha- thalassemia intermedia). Individuals with structural variant of hemoglobin especially Hemoglobin S and Hemoglobin C associated with "alpha" or "beta" thalassemia in heterozygous condition may also present with similar features of NTDT. NTDT patients are not immune to the development of transfusion unrelated complications in the long run. These hereditary chronic hemolytic anemias are still under-recognized in developing countries like India, where the disease burden might be high causing significant morbidity. The pathophysiologic hallmark that characterizes this group of disorders (ineffective erythropoiesis, hemolysis, chronic anemia) leads to a number of serious complications, similar to transfusion dependent thalassemia. So, timely diagnosis and institution of appropriate preventive/remedial measures as well as education of patient population can help decrease the morbidity to a significant extent. In the present review, focus will be on the pathophysiological mechanisms and available management options of NTDT from a developing country perspective like India. PMID- 26133181 TI - Molecular Subgrouping of Medulloblastoma: Impact Upon Research and Clinical Practice. AB - Medulloblastoma, the most common primary pediatric malignant brain tumor is a molecularly heterogeneous disease with different developmental origins, distinct phenotypes, diverse biological behaviour, and contrasting clinical outcomes. The current clinico-radiological risk-classification fails to take account of this heterogeneity and existent prognostic variability. It is widely accepted that dysregulation of normal developmental processes constitute a key mechanism of tumorigenesis in at least a subset of medulloblastomas. Several attempts at biological classification have successfully identified distinct subgroups with subgroup-specific gene signatures, demographics, histologic subtypes, and rates of metastases. Several research groups have classified medulloblastoma into molecular subgroups using a variety of different genomic approaches and platforms such as gene expression profiling, microRNA profiling and methylation arrays. Recently, a consensus has emerged that classifies medulloblastoma into four distinct molecular subgroups named as wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4 respectively. However, such integrative approaches have limited applicability in the clinic due to the need of fresh-frozen tissues and elaborate molecular biology tools. In parallel, some groups have proposed and validated traditional antibody-based approaches using immunohistochemistry on archival specimen for rapid and reliable molecular subgrouping to be applied in any basic neuropathology laboratory. Heterogeneity within each of these four consensus subgroups has also been demonstrated that needs to be considered in the design of future clinical trials. There is a compelling need to integrate molecular biomarkers with clinico-pathologic outcome indicators to refine risk stratification as well as develop novel molecularly targeted agents for optimizing therapeutic index and personalizing therapy. PMID- 26133182 TI - New Insights into the Surgical Management of Tetralogy of Fallot: Physiological Fundamentals and Clinical Relevance. AB - The surgical treatment of tetralogy of Fallot can be considered as a success story in the history of congenital heart diseases. Since the early outcome is no longer the main issue, the focus moved to the late sequelae of TOF repair, i.e. the pulmonary insufficiency and the secondary adaptation of the right ventricle. This review provides recent insights into the pathophysiological alterations of the right ventricle in relation to the reconstruction of the right ventricular outflow tract after repair of tetralogy of Fallot. Its clinical relevance is documented by addressing the policy changes regarding the optimal management at the time of surgical repair as well as properly defining criteria and timing for late pulmonary valve implantation. PMID- 26133184 TI - Increased calorie consumption corresponds to weight gain levels across the globe. PMID- 26133183 TI - The g.-165 T>C Rather than Methylation Is Associated with Semen Motility in Chinese Holstein Bulls by Regulating the Transcriptional Activity of the HIBADH Gene. AB - The 3-hydroxyisobutyrate dehydrogenase (HIBADH) is regarded as a human sperm motility marker. However, the molecular mechanisms involved in the regulation of expression of the HIBADH gene in bulls remain largely unknown. HIBADH was detected in the testis, epididymis, and sperm via reverse transcription polymerase chain reaction and Western blot analysis. It is also expressed in the seminiferous epithelium, spermatids, and the entire epididymis, as detected by immunohistochemistry. Furthermore, HIBADH was expressed in the neck-piece and mid piece of bull spermatids, as shown in the immunofluorescence assay. Using serially truncated bovine HIBADH promoters and luciferase constructs, we discovered an 878 bp (-703 bp to +175 bp) fragment that constitutes the core promoter region. One SNP g.-165 T>C of HIBADH was identified and genotyped in 307 Chinese Holstein bulls. Correlation analysis revealed that bulls with the TT genotype had higher initial sperm motility than those with the CC genotype (P < 0.05). Furthermore, the T- or C-containing loci (designated as pGL3-T and pGL3-C) were transiently transfected into MLTC-1 to test the effect of SNP on HIBADH expression. The luciferase reporter assay showed that the pGL3-T genotype exhibited 58% higher transcriptional activity than the pGL3-C genotype (P < 0.05). The bisulfite sequencing analysis revealed that the methylation pattern of the core promoter presented hypomethylation in the ejaculated semen in high motility and low-motility bulls. The results demonstrated for the first time that the g.-165 T>C rather than methylation in the 5'-flanking region could affect the bovine sperm motility through the regulation of HIBADH gene transcriptional activity. PMID- 26133185 TI - Recent advancements in structured-illumination microscopy toward live-cell imaging. AB - Fluorescence microscopy allows us to observe fluorescently labeled molecules in diverse biological processes and organelle structures within living cells. However, the diffraction limit restricts its spatial resolution to about half of its wavelength, limiting the capability of biological observation at the molecular level. Structured-illumination microscopy (SIM), a type of super resolution microscopy, doubles the spatial resolution in all three dimensions by illuminating the sample with a patterned excitation light, followed by computer reconstruction. SIM uses a relatively low illumination power compared with other methods of super-resolution microscopy and is easily available for multicolor imaging. SIM has great potential for meeting the requirements of live-cell imaging. Recent developments in diverse types of SIM have achieved higher spatial (~50 nm lateral) and temporal (~100 Hz) resolutions. Here, we review recent advancements in SIM and discuss its application in noninvasive live-cell imaging. PMID- 26133186 TI - What Role Do Changes in the Demographic Composition Play in the Declining Trends in Alcohol Consumption and the Increase of Non-drinkers Among Swedish Youth? A Time-series Analysis of Trends in Non-drinking and Region of Origin 1971-2012. AB - AIM: Non-drinkers among youth in Sweden have increased markedly during the last 15 years. The aim of this study is to investigate the temporal association between region of origin among Swedish youth and rates of non-drinking. DATA AND METHOD: Data on non-drinkers were obtained from The Swedish Council on Information and Other drugs (CAN) yearly school surveys among Swedish ninth-grade students over the period 1971-2013. Annual data of region of origin for 1968-2012 has been compiled from Statistics Sweden (SCB) and consists of all 15-year-olds in Sweden and their region of birth; Sweden, The Nordic Countries, Europe, The Middle East and the rest of the world. Autoregressive Integrated Moving Average (ARIMA) modelling was applied in order to estimate these associations. RESULTS: Descriptive results revealed a change in the demography of Swedish 15- to 16-year olds. In the early 1990s 1% of Swedish 15- to 16-year-olds were born in a Middle East country, this proportion increased to 6% in 2012. Furthermore, those born in the rest of the world (non-European or non-Nordic countries) increased from 1% to almost 4%. Similarly, the trend of non-drinkers increased from about 20% to more than 40% among Swedish 15- to 16-year-olds during the same period. However, a more thorough analysis using ARIMA modelling revealed no significant association between rates of region of origin and non-drinking. CONCLUSION: The marked increase in non-drinkers during the last 15 years is not associated to changes in the demographic composition, in terms of region of origin, among Swedish youth. PMID- 26133187 TI - Changing of the Guard--Greetings from the New Editor in Chief. PMID- 26133188 TI - Depletion of enteroantigen-activated CD4+ T cells: effects on proliferation and pathogenicity. AB - Naive CD4(+) T cells depleted of natural Treg (CD25(+)) cells proliferate extensively when exposed to a fecal extract [enteroantigen (eAg)] pulsed on antigen-presenting cells (APC). When transplanted into SCID recipient mice, the CD25-depleted T cells induce a chronic colitis with a lethal course. We observed here that if T cells, pre-activated for 48h by eAg from BALB/c or SCID mice, are removed and then reexposed to either of the two sources of antigen, these T cells have completely lost their anti-eAg proliferative capacity in vitro. This observation indicates that eAgs derived from Balb/c and SCID mice are recognized by similar subsets of T cells. However, when transferred into SCID mice, eAg activation-depleted T cells are still capable of inducing a severe colitis fully comparable with the disease induced by naive CD4(+) T cells. PMID- 26133190 TI - Transverse Movement of the Median Nerve in the Carpal Tunnel during Wrist and Finger Motion in Patients with Carpal Tunnel Syndrome. AB - Carpal tunnel syndrome (CTS) is the most common peripheral compression neuropathy of the upper extremity. Repetitive wrist and finger motion has been suggested as a major factor of pathogenesis of CTS. However, little is known about the pathomechanics of CTS. We aimed to evaluate the movement of the median nerve in the carpal tunnel during wrist and finger motions using transverse ultrasound in 21 patients with CTS (5 men and 16 women with mean age 69.0 years). We examined quantitatively the median nerve location as a coordinate within the carpal tunnel at varied wrist positions with all fingers full extension and flexion respectively in the affected and unaffected sides. We thus found that at all wrist positions during finger motion, the median nerve moved significantly more ulnopalmarly in the affected side compared to the unaffected side (p < 0.05). Especially, at the wrist palmar-flexion position as a provocative test, the nerve moved significantly (p < 0.05) the most ulnopalmarly among all wrist positions in the affected side. The nerve was the most strongly compressed against the transverse carpal ligament by the flexor tendons. Additionally, the displacement amount of the nerve in the dorsal-palmar direction was significantly smaller in the affected side than in the unaffected side. These findings indicate that such a pattern of nerve movement has the potential to distinguish affected from unaffected individuals. This ultrasound information could be useful in better understanding of the pathomechanics of CTS, and in further improvement of diagnosis and treatment for CTS. PMID- 26133189 TI - Patient doses from CT examinations in Turkey. AB - PURPOSE: We aimed to establish the first diagnostic reference levels (DRLs) for computed tomography (CT) examinations in adult and pediatric patients in Turkey and compare these with international DRLs. METHODS: CT performance information and examination parameters (for head, chest, high-resolution CT of the chest [HRCT-chest], abdominal, and pelvic protocols) from 1607 hospitals were collected via a survey. Dose length products and effective doses for standard patient sizes were calculated from the reported volume CT dose index (CTDIvol). RESULTS: The median number of protocols reported from the 167 responding hospitals (10% response rate) was 102 across five different age groups. Third quartile CTDIvol values for adult pelvic and all pediatric body protocols were higher than the European Commission standards but were comparable to studies conducted in other countries. CONCLUSION: The radiation dose indicators for adult patients were similar to those reported in the literature, except for those associated with head protocols. CT protocol optimization is necessary for adult head and pediatric chest, HRCT-chest, abdominal, and pelvic protocols. The findings from this study are recommended for use as national DRLs in Turkey. PMID- 26133191 TI - Socket reaction moments in transtibial prostheses during walking at clinically perceived optimal alignment. AB - BACKGROUND AND AIM: The socket reaction moments are directly measured at the base of a socket and may be useful for fitting a prosthesis. Previous studies have focused on the effect of prosthetic alignment changes on them. The aim of this study was to explore their range at clinically perceived optimal alignment by investigating the individual differences. TECHNIQUE: In total, 11 amputees using unilateral transtibial prostheses with solid-ankle-cushion-heel (SACH) feet were recruited. The socket reaction moments were measured using a custom instrumented prosthesis alignment component and plotted. Eight variables that were related to their magnitude (N m/kg) and timing (% stance of event) as well as cadence (steps/minute) were calculated for each amputee. Their mean, standard deviation, maximum value, minimum value, and range were subsequently analyzed. DISCUSSION: This study may serve as a foundation to explore the range of individual differences in socket reaction moments in transtibial prostheses. CLINICAL RELEVANCE: Socket reaction moments can be conveniently measured in the clinical setting. Prosthetists could potentially use them as one of the criteria to align prosthesis in addition to observational gait analysis and amputees perception. PMID- 26133192 TI - The influence of thermoplastic thoraco lumbo sacral orthoses on standing balance in subjects with idiopathic scoliosis. AB - BACKGROUND: Idiopathic scoliosis patients have postural equilibrium problems. OBJECTIVE: The objective of this study was to assess postural control in subjects with idiopathic scoliosis following a 4-month intervention in an unbraced position. STUDY DESIGN: Quasi-experimental. METHODS: Eight healthy girls and eight girls with idiopathic scoliosis took part. A Kistler force platform was used with a frequency of 100 Hz for recording data. The center of pressure was recorded in different positions out of brace for scoliosis and healthy subjects. Test conditions were single limb and double limb stance, with eyes open and closed, and foam and rigid surfaces. RESULTS: The data reflected a weak balance of idiopathic scoliosis subjects compared to healthy subjects. After 1 and 4 months of wearing the brace, center of pressure and center of gravity sway increased in the majority of the tests, although there were no significant differences in any of the test conditions (p > 0.05). While the center of pressure sway in medio-lateral direction decreased after 4 months of wearing a brace, in other variables center of pressure and center of gravity sway increased. CONCLUSION: Idiopathic scoliosis patients have weak balance in comparison to healthy subjects. In addition, following a period of 4 months of wearing a brace, balance parameters in the scoliosis subjects did not improve. The results show that we need more follow-up of orthoses wearing in idiopathic scoliosis subjects and suggest more studies at least 1-year follow-up to identify the efficiency of brace wear on balance. CLINICAL RELEVANCE: Scoliosis can alter postural stability and balance performance during quiet standing. Spinal deformity can alter a subject's ability to compensate for postural changes and cause gait deviations. This study investigated balance differences between the healthy and idiopathic scoliosis patients and the results of thoraco lumbo sacral orthosis brace wear. It might provide some new insight into the conservative treatment of idiopathic scoliosis patients for clinicians and researchers. PMID- 26133193 TI - Highly branched RuO2 nanoneedles on electrospun TiO2 nanofibers as an efficient electrocatalytic platform. AB - Highly single-crystalline ruthenium dioxide (RuO2) nanoneedles were successfully grown on polycrystalline electrospun titanium dioxide (TiO2) nanofibers for the first time by a combination of thermal annealing and electrospinning from RuO2 and TiO2 precursors. Single-crystalline RuO2 nanoneedles with relatively small dimensions and a high density on electrospun TiO2 nanofibers are the key feature. The general electrochemical activities of RuO2 nanoneedles-TiO2 nanofibers and Ru(OH)3-TiO2 nanofibers toward the reduction of [Fe(CN)6](3-) were carefully examined by cyclic voltammetry carried out at various scan rates; the results indicated favorable charge-transfer kinetics of [Fe(CN)6](3-) reduction via a diffusion-controlled process. Additionally, a test of the analytical performance of the RuO2 nanoneedles-TiO2 nanofibers for the detection of a biologically important molecule, hydrogen peroxide (H2O2), indicated a high sensitivity (390.1 +/- 14.9 MUA mM(-1) cm(-2) for H2O2 oxidation and 53.8 +/- 1.07 MUA mM(-1) cm(-2) for the reduction), a low detection limit (1 MUM), and a wide linear range (1 1000 MUM), indicating H2O2 detection performance better than or comparable to that of other sensing systems. PMID- 26133194 TI - The evaluation of cardiac tamponade risk in patients with pericardial effusion detected by non-gated chest CT. AB - BACKGROUND: Although pericardial effusion is often identified using non-gated chest computed tomography (CT), findings predictive of cardiac tamponade have not been adequately established. PURPOSE: To determine the findings predictive of clinical cardiac tamponade in patients with moderate to large pericardial effusion using non-gated chest CT. MATERIAL AND METHODS: We performed a retrospective analysis of 134 patients with moderate to large pericardial effusion who were identified from among 4581 patients who underwent non-gated chest CT. Cardiac structural changes, including right ventricular outflow tract (RVOT), were qualitatively evaluated. The inferior vena cava ratio with hepatic (IVCupp) and renal portions (IVClow) and effusion size were measured. The diagnostic performance of each structural change was calculated, and multivariate analysis was used to determine the predictors of cardiac tamponade. RESULTS: Of the 134 patients (mean age, 70.3 years; 64 men), 37 (28%) had cardiac tamponade. The sensitivity and specificity were 76% and 74% for RVOT compression; 87% and 84% for an IVClow ratio >=0.77; and 60% and 77% for an effusion size >=25.5 mm, respectively. Multivariate logistic regression analysis demonstrated that RVOT compression, an IVClow ratio >=0.77, and an effusion size >=25.5 mm were independent predictors of cardiac tamponade. The combination of these three CT findings had a sensitivity, specificity, and accuracy of 81%, 95%, and 91%, respectively. CONCLUSION: In patients with moderate to large pericardial effusion, non-gated chest CT provides additional information for predicting cardiac tamponade. PMID- 26133195 TI - Urgent transcatheter arterial embolization for the treatment of ruptured renal angiomyolipoma with spontaneous hemorrhage. AB - Background The rich neovascularization of renal angiomyolipoma (AML) has a tendency for spontaneous rupture with subsequent hemorrhage. Nephrectomy or nephron-sparing surgery has rarely been used as a primary treatment in urgent situations. Purpose To evaluate the safety and long-term outcomes for patients treated by urgent transcatheter arterial embolization (TAE) for spontaneous ruptured renal AML with severe hemorrhage. Material and Methods A retrospective evaluation was performed of 25 renal AML cases with spontaneous hemorrhage confirmed by imaging. Polyvinyl alcohol (PVA) particles and coils of multiple sizes were used to embolize the spontaneous renal AML ruptures. Results The technical success rate of TAE was 96% (24/25). One week post-TAE, 1 patient with recurrent hemorrhage underwent emergency nephrectomy. Minor complications affected 16 patients with post-embolization syndrome; 15 patients resolved using conservative measures and one patient received nephrectomy post TAE 1 week later. All patients were followed up for 24-72 months (median, 50.2 months). Surgical treatment was avoided for 92% (23/25) of patients, and the re-embolization rate was 0% at 2 years post TAE. In the 23 patients without surgical treatment, the mean maximum diameter of renal AML was reduced from 12.4 +/- 5.5 cm to 6.3 +/- 2.5 cm and no hemorrhage occurred during follow-up. Conclusion Urgent TAE is a technically feasible and minimally invasive procedure for controlling severe hemorrhage and preservation of renal function following spontaneous ruptured renal AML. PMID- 26133196 TI - Metabolic Engineering of Synechocystis sp. PCC 6803 for Production of the Plant Diterpenoid Manoyl Oxide. AB - Forskolin is a high value diterpenoid with a broad range of pharmaceutical applications, naturally found in root bark of the plant Coleus forskohlii. Because of its complex molecular structure, chemical synthesis of forskolin is not commercially attractive. Hence, the labor and resource intensive extraction and purification from C. forskohlii plants remains the current source of the compound. We have engineered the unicellular cyanobacterium Synechocystis sp. PCC 6803 to produce the forskolin precursor 13R-manoyl oxide (13R-MO), paving the way for light driven biotechnological production of this high value compound. In the course of this work, a new series of integrative vectors for use in Synechocystis was developed and used to create stable lines expressing chromosomally integrated CfTPS2 and CfTPS3, the enzymes responsible for the formation of 13R-MO in C. forskohlii. The engineered strains yielded production titers of up to 0.24 mg g( 1) DCW 13R-MO. To increase the yield, 13R-MO producing strains were further engineered by introduction of selected enzymes from C. forskohlii, improving the titer to 0.45 mg g(-1) DCW. This work forms a basis for further development of production of complex plant diterpenoids in cyanobacteria. PMID- 26133197 TI - Preferences for Social Support During Social Evaluation in Men: The Role of Worry About a Relationship Partner's Negative Evaluation. AB - Most individuals seek proximity to support figures when distressed. However, individuals may not want a relationship partner present when their performance is being evaluated during difficult tasks, because they would worry about their partner's evaluation. Male participants' performance on difficult tasks was evaluated by critical judges. Then participants were asked if they wanted a close relationship partner present when they come back for similar tasks the following week. Worry about a partner's negative evaluation predicted not wanting the partner present. The direct effect of attachment-related anxiety on wanting more support was suppressed by its indirect effects in the opposite direction through distress and worry about a partner's negative evaluation. The indirect effect of attachment-related avoidance on wanting less support through distress and worry about partner's negative evaluation was also significant. Findings contribute to our understanding of preferences for support and effects on well-being. PMID- 26133198 TI - But, I Signed the Form. PMID- 26133199 TI - Decreased Radiation Exposure and Increased Efficacy in Extracorporeal Lithotripsy Using a New Ultrasound Stone Locking System. AB - PURPOSE: To compare fluoroscopy duration, radiation dose, and efficacy of two ultrasound stone localization systems during extracorporeal shockwave lithotripsy (SWL) treatment. PATIENTS AND METHODS: Monocentric prospective data were obtained from patients consecutively treated for renal stones using the Sonolith((r)) i sys (EDAP TMS) lithotripter, with fluoroscopy combined with ultrasound localization using an "outline" Automatic Ultrasound Positioning Support (AUPS) (group A), or the "free-line" Visio-Track (VT) (EDAP-TMS) hand-held three dimensional ultrasound stone locking system (group B). Efficacy rate was defined as the within-groups proportion stone free or with partial stone fragmentation not needing additional procedures. Statistical analysis used Pearson chi-square tests for categoric variables, nonparametric Mann-Whitney tests for continuous variables, and linear regression for operator learning curve with VT. Continuous variables were reported as median (range) values. RESULTS: Patients in group A (n=73) and group B (n=81) were comparable in baseline characteristics (age, kidney stone size, others) and in SWL application (duration, number of shocks, energy [Joules]). During SWL, the median (range) duration (seconds) of radiation exposure was 159.5 (0-690) in group A and 3.5 (0-478) in group B (P<0.001) and irradiation dose (mGy.cm(2)), 10598 (0-54843) in group A and 163 (0-13926) in group B (P<0.001). Fluoroscopy time significantly decreased with operator experience using VT. The efficacy rate was 54.5% in group A and 79.5% in group B (P=0.001). CONCLUSION: VT significantly reduced fluoroscopy use during SWL and the duration and dose of patient exposure to ionizing radiation. Stone treatment efficacy was significantly greater with VT mainly because of a better real-time monitoring of the stone. PMID- 26133200 TI - Partially covered versus uncovered self-expandable nitinol stents with anti migration properties for the palliation of malignant distal biliary obstruction: A randomized controlled trial. AB - OBJECTIVE: Covered self-expandable metal stents (SEMSs) are increasingly used as alternatives to uncovered SEMSs for the palliation of inoperable malignant distal biliary obstruction to counteract tumor ingrowth. We aimed to compare the outcomes of partially covered and uncovered SEMSs with identical mesh structures and anti-migration properties, such as low axial force and flared ends. MATERIALS AND METHODS: One hundred and three patients who were diagnosed with inoperable malignant distal biliary obstruction between January 2006 and August 2013 were randomly assigned to either the partially covered (n = 51) or uncovered (n = 52) SEMS group. RESULTS: There were no significant differences in the cumulative stent patency, overall patient survival, stent dysfunction-free survival and overall adverse events, including pancreatitis and cholecystitis, between the two groups. Compared to the uncovered group, stent migration (5.9% vs. 0%, p = 0.118) and tumor overgrowth (7.8% vs. 1.9%, p = 0.205) were non-significantly more frequent in the partially covered group, whereas tumor ingrowth showed a significantly higher incidence in the uncovered group (5.9% vs. 19.2%, p = 0.041). Stent migration in the partially covered group occurred only in patients with short stenosis of the utmost distal bile duct (two in ampullary cancer, one in bile duct cancer), and did not occur in any patients with pancreatic cancer. CONCLUSIONS: For the palliation of malignant distal biliary obstruction, endoscopic placement of partially covered SEMSs with anti-migration designs and identical mesh structures to uncovered SEMSs failed to prolong cumulative stent patency or reduce stent migration. PMID- 26133201 TI - Sex Differences in Gray Matter Changes and Brain-Behavior Relationships in Patients with Stimulant Dependence. AB - PURPOSE: To investigate whether sex modulates the effects of stimulant dependence on gray matter volume (GMV) in patients who have achieved long-term abstinence and to characterize how sex modulates GMV according to specific behavioral measures, such as dependence symptom count, behavioral approach, and impulsivity. MATERIALS AND METHODS: Colorado Multiple Institutional Review Board approval and informed consent were obtained. In this prospective parallel group study, 127 age and sex-matched participants (68 control subjects [28 women, 40 men] and 59 patients with stimulant dependence [28 women, 31 men]) underwent T1-weighted spoiled gradient-echo inversion recovery magnetic resonance imaging of the brain at 3 T. Images were segmented by using voxel-based morphometric software. After adjustment for age, education, and head size, the effects of group according to sex on GMV and main effects were analyzed throughout the whole brain by using an analysis of covariance family-wise cluster corrected for multiple comparisons, with a threshold P value of less than .05. Dependence symptom count and behavioral measurements were correlated with GMV in the whole brain and in five a priori regions of interest. RESULTS: The effects of group according to sex on GMV were significant in numerous regions (P < .001). Compared with female control subjects, women with stimulant dependence had significantly lower GMV in widespread brain regions (P < .001). There were no significant differences in GMV between male control subjects and men with stimulant dependence (P = .625). Dependence symptom count negatively correlated with GMV in the nucleus accumbens in women (left: r = -0.364, P = .047; right: r = -0.407, P = .031) but not in men (left: r = -0.063, P = .737; right: r = -0.174, P = .349). Behavioral approach (P = .002) and impulsivity (P = .013) correlated negatively with frontal and temporal GMV changes in women with stimulant dependence but not in the other groups. CONCLUSION: Vast changes in GMV were observed in women with stimulant dependence after prolonged abstinence, but were not observed in men. Sexual dimorphism in drug-related neuroanatomic changes and brain-behavior relationships may be mechanisms underlying the difference in clinical profiles of addiction between women and men. PMID- 26133202 TI - Medicinal Plants Used by the Nicobarese Inhabiting Little Nicobar Island of the Andaman and Nicobar Archipelago, India. AB - BACKGROUND: This study is an attempt to document the medicinal plants used by the tribal community of Little Nicobar Island. Despite modern healthcare facilities, tribals often consume medicinal herbs, with traditional knowledge practitioners (TKPs) serving as local medical experts. OBJECTIVES: The aim is to conduct an ethnomedicinal survey among the Nicobarese, whose medicinal practices are yet to be documented. METHODS: Field research was conducted in all five villages of Little Nicobar Island, situated in the southernmost part of the Andaman and Nicobar Archipelago, during 2012-2013. Seven TKPs were interviewed using a questionnaire-guided ethnomedicinal survey protocol. The data obtained were analyzed using the informant consensus factor (ICF) and use value. Voucher specimens of all the cited plant species were deposited at the Regional Medical Research Centre (Indian Council of Medical Research), Port Blair. RESULTS: Uses of 34 medicinal plant species, belonging to 23 families encompassing 32 genera, were recorded during the survey. These 34 species are employed to treat a total of 16 ailments. The highest ICF (1.00) was obtained for respiratory diseases. The Euphorbiaceae family exhibited the highest number of citations, and plants with the highest use values were Glochidion calocarpum Kurz, Senna occidentalis (L.) Link, Ocimum tenuiflorum L., and Passiflora suberosa L. Of the medicinal plants reported, the most common growth form was herbs. Remedies were generally prepared using water. The medicinal plant preparations were administered topically or orally. INTERPRETATION AND CONCLUSIONS: Traditional knowledge of herbal medicines is handed down orally through generations. These plants attained a significant role under the healthcare of the Nicobarese residing in Little Nicobar Island. Efforts to ensure their documentation are necessary in order to prevent its loss, either because of natural calamities or lack of interest among younger generations in carrying out their tradition. PMID- 26133203 TI - Consensus Recommendations to NCCIH from Research Faculty in a Transdisciplinary Academic Consortium for Complementary and Integrative Health and Medicine. AB - BACKGROUND: This commentary presents the most impactful, shared priorities for research investment across the licensed complementary and integrative health (CIH) disciplines according to the Academic Consortium for Complementary and Alternative Health Care (ACCAHC). These are (1) research on whole disciplines; (2) costs; and (3) building capacity within the disciplines' universities, colleges, and programs. The issue of research capacity is emphasized. DISCUSSION: ACCAHC urges expansion of investment in the development of researchers who are graduates of CIH programs, particularly those with a continued association with accredited CIH schools. To increase capacity of CIH discipline researchers, we recommend National Center for Complementary and Integrative Health (NCCIH) to (1) continue and expand R25 grants for education in evidence-based healthcare and evidence-informed practice at CIH schools; (2) work to limit researcher attrition from CIH institutions by supporting career development grants for clinicians from licensed CIH fields who are affiliated with and dedicated to continuing to work in accredited CIH schools; (3) fund additional stand-alone grants to CIH institutions that already have a strong research foundation, and collaborate with appropriate National Institutes of Health (NIH) institutes and centers to create infrastructure in these institutions; (4) stimulate higher percentages of grants to conventional centers to require or strongly encourage partnership with CIH institutions or CIH researchers based at CIH institutions, or give priority to those that do; (5) fund research conferences, workshops, and symposia developed through accredited CIH schools, including those that explore best methods for studying the impact of whole disciplines; and (6) following the present NIH policy of giving priority to new researchers, we urge NCCIH to give a marginal benefit to grant applications from CIH clinician-researchers at CIH academic/research institutions, to acknowledge that CIH concepts require specialized expertise to translate to conventional perspectives. SUMMARY: We commend NCCIH for its previous efforts to support high-quality research in the CIH disciplines. As NCCIH develops its 2016-2020 strategic plan, these recommendations to prioritize research based on whole disciplines, encourage collection of outcome data related to costs, and further support capacity building within CIH institutions remain relevant and are a strategic use of funds that can benefit the nation's health. PMID- 26133204 TI - A Yoga Intervention Program for Patients Suffering from Symptoms of Posttraumatic Stress Disorder: A Qualitative Descriptive Study. AB - OBJECTIVE: To understand how individuals with symptoms of posttraumatic stress disorder (PTSD) perceive a trauma-sensitive Kundalini yoga (KY) program. METHODS: Digitally recorded telephone interviews 30-60 minutes in duration were conducted with 40 individuals with PTSD participating in an 8-week KY treatment program. Interviews were transcribed verbatim and analyzed using qualitative thematic analysis techniques. RESULTS: Qualitative analysis identifies three major themes: self-observed changes, new awareness, and the yoga program itself. Findings suggest that participants noted changes in areas of health and well-being, lifestyle, psychosocial integration, and perceptions of self in relation to the world. Presented are practical suggestions for trauma-related programming. CONCLUSION: There is a need to consider alternative and potentially empowering approaches to trauma treatment. Yoga-related self-care or self-management strategies are widely accessible, are empowering, and may address the mind-body elements of PTSD. PMID- 26133205 TI - Challenges to Enrollment and Participation in Mindfulness-Based Stress Reduction Among Veterans: A Qualitative Study. AB - BACKGROUND: Mindfulness-Based Stress Reduction (MBSR) is associated with reduced depressive symptoms, quality of life improvements, behavioral activation, and increased acceptance among veterans. This study was conducted to increase the reach and impact of a veterans' MBSR program by identifying barriers to enrollment and participation to inform modifications in program delivery. OBJECTIVE: Verify or challenge suspected barriers, and identify previously unrecognized barriers, to enrollment and participation in MBSR among veterans. DESIGN: A retrospective qualitative analysis of semistructured interviews. SETTING/LOCATION: VA Puget Sound Health Care System (Seattle, WA). SUBJECTS: 68 interviewed, and 48 coded and analyzed before reaching saturation. APPROACH: Content analysis of semistructured interviews. RESULTS: Of the participants who enrolled, most (78%) completed the program and described MBSR positively. Veterans identified insufficient or inaccurate information, scheduling issues, and an aversion to groups as barriers to enrollment. Participants who discontinued the program cited logistics (e.g., scheduling and medical issues), negative reactions to instructors or group members, difficulty understanding the MBSR practice purposes, and struggling to find time for the practices as barriers to completion. Other challenges (cohort dynamics, teacher impact on group structure and focus, instructor lack of military service, and physical and psychological challenges) did not impede participation; we interpreted these as growth-facilitating challenges. Common conditions among veterans (chronic pain, posttraumatic stress disorder, and depression) were not described as barriers to enrollment or completion. CONCLUSIONS: Women-only MBSR groups and tele-health MBSR groups could improve accessibility to MBSR for veterans by addressing barriers such as commute anxiety, time restrictions, and an aversion to mixed gender groups among women. Educating MBSR teachers about veteran culture and health challenges faced by veterans, adding psychoeducation materials that relate mindfulness practice to conditions common among veterans, and improving visual aids for mindful movement exercises in the workbook could better accommodate veterans who participate in MBSR. PMID- 26133208 TI - Scary smart. PMID- 26133209 TI - Public policies, one health, and veterinary medicine. PMID- 26133210 TI - The Healthy Pets Healthy Families initiative as an example of one health in action. PMID- 26133206 TI - Effect of Inhaled Lavender and Sleep Hygiene on Self-Reported Sleep Issues: A Randomized Controlled Trial. AB - OBJECTIVES: To compare the effectiveness of lavender (Lavandula angustifolia) and sleep hygiene versus sleep hygiene alone on sleep quantity and sleep quality and to determine sustained effect at two-week follow-up. DESIGN: A randomized controlled trial with investigator blinding and steps taken to blind the participants. SETTING: Participants' usual sleep setting. SUBJECTS: Seventy-nine college students with self-reported sleep issues. INTERVENTIONS: The intervention took place over five nights with baseline, postintervention, and two-week follow up assessments. Both groups practiced good sleep hygiene and wore an inhalation patch on their chest at night. One group wore a patch with 55 MUl of lavender essential oil and the other group wore a blank patch. OUTCOME MEASURES: Sleep quantity was measured using a Fitbit((r)) tracker and a sleep diary, and sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance short form. RESULTS: The lavender and sleep hygiene group demonstrated better sleep quality at postintervention and two-week follow-up (PSQI p=0 .01, <0.001 and PROMIS p=0.04, 0.007, respectively). The sleep-hygiene only group also demonstrated better sleep quality but to a lesser extent (PSQI p=0.02, 0.06 and PROMIS p=0.03, 0.03, respectively). Additionally, a clinical effect was found for the lavender group at postintervention, along with a significant finding for waking feeling refreshed (p=0.01). Sleep quantity did not differ between groups. CONCLUSIONS: Lavender and sleep hygiene together, and sleep hygiene alone to a lesser degree, improved sleep quality for college students with self-reported sleep issues, with an effect remaining at follow-up. PMID- 26133211 TI - What Is Your Diagnosis? Pathological fracture secondary to primary bone neoplasia. PMID- 26133212 TI - Theriogenology Question of the Month. Enlarged ovary due to granulosa theca cell tumor. PMID- 26133213 TI - Animal Behavior Case of the Month. Compulsive disorder. PMID- 26133214 TI - Pathology in Practice. Herpesviral dermatitis. PMID- 26133215 TI - Pathology in Practice. Histiocytic sarcoma. PMID- 26133216 TI - Signalment, clinical features, echocardiographic findings, and outcome of dogs and cats with ventricular septal defects: 109 cases (1992-2013). AB - OBJECTIVE: To determine the signalment, clinical features, echocardiographic findings, and outcome of dogs and cats with ventricular septal defects (VSDs). DESIGN: Retrospective case series. ANIMALS: 56 dogs and 53 cats with VSDs. PROCEDURES: Medical records of dogs and cats with VSDs diagnosed by means of conventional and Doppler echocardiography were reviewed. Signalment, clinical status, echocardiographic findings, and outcome data were recorded. Variables of interest were analyzed for the study population and subgroups according to species and clinical status. RESULTS: VSDs were isolated (ie, solitary defects) in 53 of 109 (48.6%) patients. Most (82/109 [75.2%]) VSDs were membranous or perimembranous. Terriers and French Bulldogs were commonly represented canine breeds. Most isolated VSDs were subclinical (43/53 [81%]) and had a pulmonary-to systemic flow ratio < 1. 5 (24/32 [75%]). The VSD diameter and VSD-to-aortic diameter ratio were significantly correlated with pulmonary-to-systemic flow ratio in dogs (r = 0.529 and r = 0.689, respectively) and in cats (r = 0.713 and r = 0.829, respectively). One dog underwent open surgical repair for an isolated VSD and was excluded from survival analysis. Of the remaining animals with isolated VSDs for which data were available (37/52 [71%]), no subclinically affected animals developed signs after initial diagnosis, and median age at death from all causes was 12 years. CONCLUSIONS AND CLINICAL RELEVANCE: Most dogs and cats with isolated VSDs had a long survival time; few had clinical signs at diagnosis, and none with follow-up developed clinical signs after diagnosis. PMID- 26133217 TI - Putative precipitating factors for hepatic encephalopathy in dogs: 118 cases (1991-2014). AB - OBJECTIVE: To elucidate the relationship between plasma ammonia concentration and severity of hepatic encephalopathy and determine whether factors that precipitate hepatic encephalopathy in humans are associated with the presence of clinical signs of hepatic encephalopathy in dogs previously treated for the disease. DESIGN: Retrospective case series. ANIMALS: 118 dogs with hepatic encephalopathy. PROCEDURES: The medical records database of a veterinary teaching hospital was searched for records of dogs in which hepatic encephalopathy was diagnosed between October 1, 1991, and September 1, 2014. Hepatic encephalopathy severity was graded on a 5-point scale, and the correlation between disease severity and plasma ammonia concentration was determined. Respective associations between hepatic encephalopathy and systemic inflammatory response syndrome, gastrointestinal hemorrhage, dietary indiscretion, constipation, furosemide treatment, azotemia, hypokalemia, hyponatremia, alkalosis, and hyperammonemia were assessed by Fisher exact tests followed by multivariable logistic regression. RESULTS: Severity of hepatic encephalopathy at hospital admission was not significantly correlated with plasma ammonia concentration. Dogs treated for hepatic encephalopathy prior to hospital admission were significantly less likely to have clinical signs of the disease at hospital admission, compared with dogs that were not treated for the disease (OR, 0.36; 95% confidence interval, 0.17 to 0.78). None of the putative precipitating factors for hepatic encephalopathy were significantly associated with the presence of clinical signs of the disease at hospital admission. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that hepatic encephalopathy treatment alleviated clinical signs of the disease. Further investigation is necessary to identify precipitating factors for hepatic encephalopathy in dogs. PMID- 26133218 TI - Surgically planned versus histologically measured lateral tumor margins for resection of cutaneous and subcutaneous mast cell tumors in dogs: 46 cases (2010 2013). AB - OBJECTIVE: To compare preplanned lateral surgical margins and measured lateral histologic margins for cutaneous and subcutaneous mast cell tumor (MCT) resections in dogs. DESIGN: Retrospective case series. SAMPLE: 51 biopsy specimens from dogs (n = 46) with MCTs. PROCEDURES: All canine patients that underwent curative-intent surgical resection of cutaneous or subcutaneous MCTs from January 1, 2010, through June 30, 2013, with complete medical records including signalment, body condition score (BCS), surgery report (with measured surgical margins), and histopathology report were included. The surgically measured tumor margins in each quadrant were grouped and compared with the corresponding histologic margins. Specimens from dogs with truncal MCTs and a BCS of 7 to 9 on a scale from 1 to 9 (ie, high) were compared with those of dogs with a BCS of 4 to 6 to evaluate effect of BCS on tissue margins. RESULTS: 51 specimens were included. Surgically mapped lateral margins differed significantly from histologically reported margins in all 4 quadrants. The mean histologic margins were 35% to 42% smaller than the surgical margins for the combined 51 specimens. A higher BCS did not significantly influence the magnitude of the decrease in lateral margins measured histologically. No significant difference was found for the magnitude of the differences between any of the 4 lateral margins. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that surgical and histologic margins may differ significantly for canine cutaneous and subcutaneous MCTs. This may be a result of tissue shrinkage following excision and fixation, extension of the MCT beyond palpable margins, or both. Histologic measurements may significantly underestimate the tumor-free margins in dogs with cutaneous and subcutaneous MCTs. PMID- 26133219 TI - Clinical disease associated with epizootic hemorrhagic disease virus in cattle in Illinois. AB - OBJECTIVE: To describe the clinical manifestation of epizootic hemorrhagic disease virus (EHDV) in cattle during an outbreak in northwestern Illinois in the fall of 2013. DESIGN: Outbreak survey. SAMPLE: 18 EHDV-affected cattle herds. PROCEDURES: Herds with confirmed EHDV-infected cattle were selected for the survey on the basis of having a manager willing to participate. A survey was developed and administered to obtain information regarding the demographics of EHDV-affected herds and the clinical signs and outcomes for EHDV-infected cattle. RESULTS: The managers of 13 beef and 5 dairy herds participated in the survey. The herds contained approximately 1,400 cattle, of which 61 were infected with EHDV and 16 died. Most cattle clinically affected with EHDV were adults, although 1 herd had 6 calves with clinical signs, and EHDV was identified during postmortem testing of 1 of those calves. Clinical signs most commonly observed were oral ulcerations or erosions, anorexia, weight loss, and lameness that typically lasted > 7 days. Of the 18 herds, 17 had wooded areas and 14 had at least 1 pond or marsh on the property. Deer were observed on the property of all farms. The EHDV outbreak in cattle coincided with an EHDV outbreak in deer in the region. CONCLUSIONS AND CLINICAL RELEVANCE: This large-scale outbreak of EHDV in US cattle was unusual because calves were affected. Because there is no way to effectively predict or prevent an EHDV outbreak in cattle, development of a vaccine for use in cattle during an outbreak would be beneficial. PMID- 26133220 TI - Financial expectations of first-year veterinary students. AB - OBJECTIVE: To assess student awareness of the financial costs of pursuing a veterinary education, to determine student expectations for financial returns of a veterinary career, and to identify associations between student debt and factors such as future career plans or personality type. DESIGN: Survey. SAMPLE: First-year veterinary students at the University of Minnesota College of Veterinary Medicine. PROCEDURES: In 2013, prior to the first day of class, all incoming first-year students received an email invitation to complete an online survey. The survey contained questions about demographics, current financial situation, current debt, expected debt at graduation, expected annual income following graduation, intent to pursue specialty training, and Myers-Briggs personality type. RESULTS: 72 of 102 (71%) students completed the survey; 65 respondents answered all relevant questions and provided usable data. Student responses for expected debt at graduation were comparable to national averages for veterinary college graduates; responses for expected annual income following graduation were lower than averages for University of Minnesota veterinary college graduates and national averages. However, students predicted even lower annual income if they did not attend veterinary college. Expected debt and expected annual income were not correlated with factors such as personality type or future career plans. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that first-year veterinary students were aware of the financial costs of their veterinary education and had realistic expectations for future salaries. For typical veterinary students, attending veterinary college appeared to be financially worthwhile, given lower expected earnings otherwise. PMID- 26133221 TI - Digital breast tomosynthesis within a symptomatic "one-stop breast clinic" for characterization of subtle findings. AB - OBJECTIVE: The aim of the study was to evaluate the diagnostic accuracy of combination of full-field digital mammography [two dimension (2D)] and digital breast tomosynthesis [DBT, three dimension (3D)] by comparing the combination with 2D imaging in a symptomatic setting. METHODS: A retrospective analysis was conducted involving 103 patients who attended symptomatic breast clinics between March 2012 and September 2012. All had subtle signs on 2D images or ultrasound. Mammographic score distribution was compared between 2D imaging and 2D + 3D imaging, followed by comparison with the gold-standard histopathology. Receiver operative characteristic curves and area under curve (AUC) were calculated for 2D imaging and the combination imaging (2D + 3D). SPSS((r)) v. 21 (IBM Corp., New York, NY; formerly SPSS Inc., Chicago, IL) was used for data analysis with p < 0.05 as statistically significant. RESULTS: M3 lesions were reduced from 91 (85.8%) to 18 (16.9%) with the combination imaging. The mean AUC +/- 95% confidence interval for 2D images alone was 0.721 (0.662-0.905) and for combined 2D and 3D images was 0.901 (0.765-1.00). The difference in AUCs between the two modalities was 0.180. CONCLUSION: DBT (3D imaging) increases diagnostic accuracy in a symptomatic breast clinic setting and reduces the number of M3 mammograms, when used as an adjuvant to 2D images. Therefore, DBT has the potential to increase workflow efficiency in a symptomatic setting by reducing benign biopsies. ADVANCES IN KNOWLEDGE: DBT reduces the number of M3 mammograms when used in the symptomatic breast setting and has the potential to reduce benign biopsies. PMID- 26133222 TI - Assessment of early therapeutic response to sorafenib in renal cell carcinoma xenografts by dynamic contrast-enhanced and diffusion-weighted MR imaging. AB - OBJECTIVE: To investigate the feasibility of dynamic contrast-enhanced MRI (DCE MRI) and diffusion-weighted MRI (DWI) in monitoring early therapeutic response to sorafenib in renal cell carcinoma (RCC) xenograft models. METHODS: Sorafenib (40 mg kg(-1)) was administered orally to BALB/c nude mice (n = 9) bearing subcutaneous tumours of human RCC ACHN xenografts. DCE-MRI and DWI were obtained 0, 1, 3 and 7 days after therapy, and DCE-MRI parameters (K(trans) and ve) and apparent diffusion coefficient (ADC) values were calculated. Tumour size and volume changes were correlated with changes in DCE-MRI parameters or ADC values after therapy. RESULTS: Following therapy, K(trans) showed a significant decrease over time (p = 0.005), whereas ve did not demonstrate significant changes between time points (p = 0.97). ADC values showed a progressive increase over time (p = 0.004). Compared with pre-therapy, K(trans) showed a significant decrease after 3 days of therapy (p = 0.039), and ADC values increased significantly after 7 days (p = 0.039). Tumour size and volume did not show significant changes during 7 days. Tumour size and volume changes were not associated with changes in DCE-MRI parameters or ADC values. CONCLUSION: DCE-MRI and DWI may show early physiological changes within 1 week after initiating sorafenib treatment on human RCC xenografts. ADVANCES IN KNOWLEDGE: The quantitative parameters of DCE-MRI and DWI may offer the potential for assessing early therapeutic response to sorafenib in clinical trials. PMID- 26133223 TI - Imaging features of poorly controlled congenital adrenal hyperplasia in adults. AB - Congenital adrenal hyperplasia (CAH) is a genetic autosomal recessive condition most frequently as a result of a mutation in the 21-hydroxylase enzyme gene. Patients with poorly controlled CAH can manifest characteristic imaging findings as a result of adrenocorticotrophic hormone stimulation or the effects of cortisol precursor excess on various target organs. We present a spectrum of imaging findings encountered in adult patients with poorly treated CAH, with an emphasis on radiological features and their clinical relevance. PMID- 26133224 TI - Evidence of dose saving in routine CT practice using iterative reconstruction derived from a national diagnostic reference level survey. AB - OBJECTIVE: To assess the influence and significance of the use of iterative reconstruction (IR) algorithms on patient dose in CT in Australia. METHODS: We examined survey data submitted to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) National Diagnostic Reference Level Service (NDRLS) during 2013 and 2014. We compared median survey dose metrics with categorization by scan region and use of IR. RESULTS: The use of IR results in a reduction in volume CT dose index of between 17% and 44% and a reduction in dose-length product of between 14% and 34% depending on the specific scan region. The reduction was highly significant (p < 0.001, Wilcoxon rank-sum test) for all six scan regions included in the NDRLS. Overall, 69% (806/1167) of surveys included in the analysis used IR. CONCLUSION: The use of IR in CT is achieving dose savings of 20-30% in routine practice in Australia. IR appears to be widely used by participants in the ARPANSA NDRLS with approximately 70% of surveys submitted employing this technique. ADVANCES IN KNOWLEDGE: This study examines the impact of the use of IR on patient dose in CT on a national scale. PMID- 26133225 TI - Splenic infarction associated with sickle cell trait at low altitude. AB - OBJECTIVE AND IMPORTANCE: Sickle cell trait is widely known to be associated with splenic infarction at high altitudes. Although textbooks and reviews imply that this complication does not occur at low altitudes, we encountered such a case and identified several previous cases in the literature. CLINICAL PRESENTATION: An 18 year-old woman with sickle cell trait who resided near sea level presented with left upper quadrant abdominal pain and was found to have multiple splenic infarcts. She was otherwise well, with no comorbidities that would predispose to hypoxemia or vascular injury. A review of the literature revealed 12 previously published cases of low-altitude splenic infarction in patients with sickle trait; 7 of those patients had comorbidities that likely predisposed to splenic infarction. INTERVENTION: None. CONCLUSION: Spontaneous splenic infarction can occur in patients with sickle trait who live at low altitudes. It is unclear whether this complication is rare, or whether it is relatively common but under recognized. PMID- 26133227 TI - Further Validation of the Pillbox Test in a Mixed Clinical Sample. AB - OBJECTIVE: The purpose of this research was to provide further criterion and construct validation of the Pillbox Test, a brief, ecologically valid measure designed to assess executive functioning(EF). METHOD: Participants were 179 older male veterans who completed the Pillbox Test as part of a neuropsychological evaluation. RESULTS: Performance on the Pillbox Test differed significantly between patients with and without dementia, with total error scores of >= 5 and >= 7 showing similar levels of sensitivity and specificity at 67% and at or near 70%, respectively. Hierarchical multiple regression analysis revealed that measures of EF predicted performance on the Pillbox Test above and beyond measures of processing speed, but not above and beyond measures in other cognitive domains. CONCLUSIONS: Findings suggest the Pillbox Test is a promising new performance-based measure of executive functioning that can discriminate between patients with and without dementia. PMID- 26133226 TI - A Minority of Patients with Type 1 Diabetes Routinely Downloads and Retrospectively Reviews Device Data. AB - BACKGROUND: In type 1 diabetes (T1D), periodic review of blood glucose and insulin dosing should be performed, but it is not known how often patients review these data on their own. We describe the proportion of patients with T1D who routinely downloaded and reviewed their data at home. MATERIALS AND METHODS: A cross-sectional survey of 155 adults and 185 caregivers of children with T1D at a single academic institution was performed. "Routine Downloaders" (downloaded four or more times in the past year) were also considered "Routine Reviewers" if they reviewed their data most of the time they downloaded from devices. Logistic regression was used to identify factors associated with being a Routine Reviewer. RESULTS: Only 31% of adults and 56% of caregivers reported ever downloading data from one or more devices, whereas 20% and 40%, respectively, were considered Routine Downloaders. Only 12% of adults and 27% of caregivers were Routine Reviewers. Mean hemoglobin A1c was lower in Routine Reviewers compared with non Routine Reviewers (7.2+/-1.0% vs. 8.1+/-1.6% [P=0.03] in adults and 7.8+/-1.4% vs. 8.6+/-1.7% [P=0.001] in children). In adjusted analysis of adults, the odds ratio of being a Routine Reviewer of one or more devices for every 10-year increase in age was 1.5 (95% confidence interval, 1.1, 2.1 [P=0.02]). For every 10 years since diabetes diagnosis, the odds ratio of being a Routine Reviewer was 1.7 (95% confidence interval, 1.2, 2.4 [P=0.01]). For caregivers, there were no statistically significant factors associated with being a Routine Reviewer. CONCLUSIONS: A minority of T1D patients routinely downloads and reviews data from their devices on their own. Further research is needed to understand obstacles, provide better education and tools for self-review, and determine if patient self review is associated with improved glycemic control. PMID- 26133228 TI - Natural co-occurrence of ochratoxin A, ochratoxin B and aflatoxins in Sicilian red wines. AB - The natural occurrence of ochratoxin A, ochratoxin B, aflatoxin B1, aflatoxin B2, aflatoxin G1 and aflatoxin G2 (OTA, OTB, AFB1, AFB2, AFG1, AFG2) in red wines was investigated by HPLC/FLD after immunoaffinity column clean-up in 57 market samples produced in Sicily (Italy). The results showed a very low incidence of these mycotoxins in analysed samples, confirming the high degree of quality and safety of Sicilian red wines. The results indicated 71.9% and 64.9% positive samples for OTA and OTB respectively, with an average level of 0.13 MUg l(-1), well below the European maximum permitted levels (MLs). The aflatoxin most frequently detected in the samples was AFG1, present in 57.9% of samples, while the other aflatoxins were rarely present. Recovery experiments were carried out on eight mycotoxin-free red wines spiked with OTA, OTB, AFB1, AFB2, AFG1 and AFG2 at two different levels. The limits of detection (LODs) in wines were 0.02 ug l( 1) for OTA, 0.04 ug l(-1) for OTB, 0.03 ug l(-1) for AFG1, AFG2 and AFB2, and 0.05 ug l(-1) for AFB1. A good correlation was found, with good performances in term of precision for the method. PMID- 26133229 TI - Involvement of Kruppel-like factor 9 in bleomycin-induced pulmonary toxicity. AB - Oxidative stress or the production of reactive oxygen species (ROS) has been implicated as an important factor in the development of bleomycin (BLM)-induced pulmonary toxicity; however, the mechanism behind the toxicity remains to be elucidated. The present study aimed to investigate the key factor involved in BLM induced toxicity. The study was conducted in human pulmonary fibroblast (HPF) cells and in a mouse model. The ROS level, cell death assay, protein and gene expression levels of Kruppel-like factor 9 (Klf9) and other associated factors were assessed. A dose-dependent increase in ROS, lipid peroxidation, cell death, and protein and mRNA expression levels of NF-E2-related transcription factor 2 (Nrf2) and Klf9 were observed in BLM-treated cells. However, the expression levels of the other antioxidant proteins assessed, including catalase, super oxide dismutase, glutathione reductase and thioredoxin reductase 2, were decreased. The expression levels of Nrf2 were decreased in cells treated with a higher concentration (>200 uM) of BLM. These results suggested that in response to increased intracellular levels of ROS, above a critical threshold, Nrf2 stimulates the expression of Klf9, resulting in a further increase in Klf9 mediated ROS production and subsequent cell death. Furthermore, the data suggested that Klf9 may be considered as an adjunctive therapeutic target for BLM induced pulmonary toxicity. PMID- 26133231 TI - Treatment of resistant influenza virus infection in a hospitalized patient with cystic fibrosis with DAS181, a host-directed antiviral. AB - We report a cystic fibrosis patient infected with influenza 2009H1N1 who had persistent viral shedding and clinical deterioration despite prolonged treatment with oseltamivir and zanamivir. The patient was diagnosed with H275Y neuraminidase inhibitor resistant influenza during treatment, thus was treated for 10 days with DAS181, an investigational host-directed inhaled sialidase fusion protein. Viral clearance occurred after 5 days of therapy and the patient became eligible for lung transplantation. Although the patient succumbed prior to receiving a transplant, this case exemplifies the potential utility of a host directed approach against influenza which has potential to become resistant to neuraminidase inhibitors. PMID- 26133230 TI - Total Synthesis of Shishijimicin A. AB - The total synthesis of the rare but extremely potent antitumor agent shishijimicin A has been achieved via a convergent strategy involving carboline disaccharide 3 and hydroxy enediyne thioacetate 4. PMID- 26133233 TI - An Evolutionary Perspective on Family Studies: Differential Susceptibility to Environmental Influences. AB - An evolutionary perspective of human development provides the basis for the differential-susceptibility hypothesis which stipulates that individuals should differ in their susceptibility to environmental influences, with some being more affected than others by both positive and negative developmental experiences and environmental exposures. This paper reviews evidence consistent with this claim while revealing that temperamental and genetic characteristics play a role in distinguishing more and less susceptible individuals. The differential susceptibility framework under consideration is contrasted to the traditional diathesis-stress view that "vulnerability" traits predispose some to being disproportionately affected by (only) adverse experiences. We raise several issues stimulated by the literature that need to be clarified in further research. Lastly, we suggest that therapy may differ in its effects depending on an individual's susceptibility. PMID- 26133232 TI - Shoot bending promotes flower bud formation by miRNA-mediated regulation in apple (Malus domestica Borkh.). AB - Flower induction in apple (Malus domestica Borkh.) trees plays an important life cycle role, but young trees produce fewer and inferior quality flower buds. Therefore, shoot bending has become an important cultural practice, significantly promoting the capacity to develop more flower buds during the growing seasons. Additionally, microRNAs (miRNAs) play essential roles in plant growth, flower induction and stress responses. In this study, we identified miRNAs potentially involved in the regulation of bud growth, and flower induction and development, as well as in the response to shoot bending. Of the 195 miRNAs identified, 137 were novel miRNAs. The miRNA expression profiles revealed that the expression levels of 68 and 27 known miRNAs were down-regulated and up-regulated, respectively, in response to shoot bending, and that the 31 differentially expressed novel miRNAs between them formed five major clusters. Additionally, a complex regulatory network associated with auxin, cytokinin, abscisic acid (ABA) and gibberellic acid (GA) plays important roles in cell division, bud growth and flower induction, in which related miRNAs and targets mediated regulation. Among them, miR396, 160, 393, and their targets associated with AUX, miR159, 319, 164, and their targets associated with ABA and GA, and flowering-related miRNAs and genes, regulate bud growth and flower bud formation in response to shoot bending. Meanwhile, the flowering genes had significantly higher expression levels during shoot bending, suggesting that they are involved in this regulatory process. This study provides a framework for the future analysis of miRNAs associated with multiple hormones and their roles in the regulation of bud growth, and flower induction and formation in response to shoot bending in apple trees. PMID- 26133234 TI - Zopiclone use associated with increased risk of acute pancreatitis: a case control study in Taiwan. AB - BACKGROUND: The purpose of this study was to assess the relationship between zopiclone use and the risk of acute pancreatitis in Taiwan. METHODS: This was a population-based case-control study. The data source was from the database of the Taiwan National Health Insurance Program since 2000-2011. We identified 5169 subjects aged 20-84 years with a first-time attack of acute pancreatitis as the patients and 20,676 sex-matched and age-matched subjects without acute pancreatitis as the controls. Active use of zopiclone was defined as subjects who received at least one prescription for zopiclone within 30 days before the date of diagnosing acute pancreatitis. The lack of zopiclone prescription was defined as 'never use'. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess the risk of acute pancreatitis associated with zopiclone use by the multivariable logistic regression model. RESULTS: After adjustment for potential confounding variables, the adjusted OR of acute pancreatitis was 2.36 for subjects with active use of zopiclone (95% CI 1.70-3.28), as compared with those with never use of zopiclone. In further analysis, as a reference of subjects with never use of zopiclone and without alcohol-related disease and biliary stone, the adjusted OR increased to 14.44 in those with active use of zopiclone and with alcohol-related disease or biliary stone (95% CI 7.47-27.89). CONCLUSIONS: Subjects actively using zopiclone are associated with increased risk of acute pancreatitis. Clinicians should take acute pancreatitis risk into account when prescribing zopiclone, particularly comorbid with alcohol-related disease or biliary stone. PMID- 26133235 TI - Total Mastectomy or Breast Conservation Therapy? How Radiation Oncologist Accessibility Determines Treatment Choice and Quality: A SEER Data-base Analysis. AB - Mastectomy and breast conservation therapy (BCT) are equivalent in survival for treatment of early stage breast cancer. This study evaluated the impact of radiation oncologist accessibility on choice of breast conserving surgery (BCS) versus mastectomy, and the appropriate receipt of radiotherapy after BCS. In the National Cancer Institute Survival, Epidemiology, and End Results data base, the authors selected breast cancer cases from 2004 to 2008 with the following criteria: T2N1M0 or less, lobular or ductal histology, and treatment with simple or partial mastectomy. We combined the Health Resources and Services Administration Area Resource File to define average radiation oncologist density (ROD) by county over the same time period. We evaluated tumor characteristics, demographic information, and ROD with respect to BCS rates and receipt of radiation therapy after BCS in univariable and multivariable analyses. In 118,773 cases analyzed, mastectomy was performed 33.2% of the time relative to BCS. After adjustment for demographic and tumor variables, the odds of having BCS versus mastectomy were directly associated with ROD (multiplicative change in odds for a single unit increase in ROD [95% CI] = 1.02 [1.01-1.03]; p < 0.001). Adjuvant radiation therapy was not administered in 28.2% of BCS cases. When adjusting for demographic and tumor variables, the odds of having BCS without adjuvant radiation were inversely associated with ROD (0.95 [0.94-0.97]; p < 0.001). We observed a direct relationship between ROD and BCS rates independent of demographic and tumor variables, and an inverse trend for omission of radiotherapy after BCS. Access to radiation oncologists may represent an important factor in surgical choice and receiving appropriate BCT in early stage breast cancer. PMID- 26133236 TI - Topical treatment with Xiaozheng Zhitong Paste alleviates bone cancer pain by inhibiting proteinase-activated receptor 2 signaling pathway. AB - Herbal analgesic Xiaozheng Zhitong Paste (XZP) and related modifications are often used in traditional Chinese medicine to manage cancer pain. However, its underlying mechanism remains unknown. To investigate the effects and mechanism of XZP on bone cancer pain in a rat model of breast cancer-induced bone pain, a bone cancer pain model was established by inoculating Walker 256 cells into Wistar rats. Bone cancer-bearing rats were topically treated with different doses of XZP or injected with 5 mg/kg of osteoprotegerin (OPG) as positive control. Bone destruction, bone mineral content (BMC) and bone mineral density (BMD) were analyzed by radiology. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were examined to determine pain levels. Trypsin, TNF-alpha and IL-1beta serum levels were determined using enzyme-linked immunosorbent assay (ELISA). Central sensitization markers such as c-Fos, GFAP, IBA1 and CGRP, as well as proteinase-activated receptor 2 (PAR2) signaling pathway mediators such as PAR2, PKC-gamma, PKA and TRPV1, were determined by quantitative RT-PCR and western blotting assay. XZP treatment significantly mitigated bone cancer-related nociceptive behavior, bone damage, BMC and BMD; and decreased radiological scores in rats. XZP treatment significantly inhibited IBA1, GFAP, c-Fos and CGRP expressions in the spinal cord; and significantly mitigated trypsin, TNF-alpha and IL-1beta serum levels. Furthermore, PAR2, PKC-gamma, PKA and TRPV1 relative mRNA levels and protein expression in bone lesions were significantly reduced in rats treated with XZP. XZP significantly alleviates breast cancer-induced bone pain by inhibiting the PAR2 signaling pathway. PMID- 26133237 TI - Dielectric charging by AFM in tip-to-sample space mode: overview and challenges in revealing the appropriate mechanisms. AB - The study of charge distribution on the surface and in the bulk of dielectrics is of great scientific interest because of the information gained on the storage and transport properties of the medium. Nevertheless, the processes at the nanoscale level remain out of the scope of the commonly used diagnostic methods. Atomic force microscopy (AFM) is currently applied for both injection and imaging of charges on dielectric thin films at the nanoscale level to answer the increasing demand for characterization of miniaturized components used in microelectronics, telecommunications, electrophotography, electrets, etc. However, the mechanisms for dielectric charging by AFM are not well documented, and an analysis of the literature shows that inappropriate mechanisms are sometimes presented. It is shown here that corona discharge, frequently pointed out as a likely mechanism for dielectric charging by AFM in tip-to-sample space mode, cannot develop in such small distances. Furthermore, a review of different mechanisms surmised to be at the origin of dielectric charging at the nanoscale level is offered. Field electron emission enhanced by thermionic emission is identified as a likely mechanism for dielectric charging at the nanoscale level. Experimental validation of this mechanism is obtained for typical electric field strengths in AFM. PMID- 26133238 TI - Costs of hospitalization in preterm infants: impact of antenatal steroid therapy. AB - OBJECTIVE: To estimate the costs of hospitalization in premature infants exposed or not to antenatal corticosteroids (ACS). METHOD: Retrospective cohort analysis of premature infants with gestational age of 26-32 weeks without congenital malformations, born between January of 2006 and December of 2009 in a tertiary, public university hospital. Maternal and neonatal demographic data, neonatal morbidities, and hospital inpatient services during the hospitalization were collected. The costs were analyzed using the microcosting technique. RESULTS: Of 220 patients that met the inclusion criteria, 211 (96%) charts were reviewed: 170 newborns received at least one dose of antenatal corticosteroid and 41 did not receive the antenatal medication. There was a 14-37% reduction of the different cost components in infants exposed to ACS when the entire population was analyzed, without statistical significance. Regarding premature infants who were discharged alive, there was a 24-47% reduction of the components of the hospital services costs for the ACS group, with a significant decrease in the length of stay in the neonatal intensive care unit (NICU). In very-low birth weight infants, considering only the survivors, ACS promoted a 30-50% reduction of all elements of the costs, with a 36% decrease in the total cost (p=0.008). The survivors with gestational age <30 weeks showed a decrease in the total cost of 38% (p=0.008) and a 49% reduction of NICU length of stay (p=0.011). CONCLUSION: ACS reduces the costs of hospitalization of premature infants who are discharged alive, especially those with very low birth weight and <30 weeks of gestational age. PMID- 26133239 TI - Galactosylated pullulan-curcumin conjugate micelles for site specific anticancer activity to hepatocarcinoma cells. AB - Galactosylated pullulan-curcumin conjugate (LANH2-Pu Ald-Cur SA) is developed for target specific delivery of curcumin to hepatocarcinoma cells by five step synthetic strategy, which includes oxidation of pullulan (Pu Ald), introduction of amino group to the targeting ligand (LANH2), grafting of the LANH2 to Pu Ald, modification of curcumin (Cur SA) and conjugation of Cur SA to pullulan. Nongalactosylated pullulan-curcumin conjugate (Pu-Cur SA) is also prepared to compare the enhancement in cytotoxicity offered by the targeting group. Both LANH2-Pu Ald-Cur SA and Pu-Cur SA conjugates could self assemble to micelle in water with hydrodynamic diameters of 355+/-9nm and 363+/-10nm, respectively. Both conjugates show spherical morphology and enhance stability of curcumin in physiological pH. Compared to Pu-Cur SA, LANH2-Pu Ald-Cur SA exhibits higher toxicity and internalization towards HepG2 cells. This indicates the enhanced uptake of LANH2-Pu Ald-Cur SA conjugate via ASGPR (asialoglycoprotein receptor) mediated endocytosis into HepG2 cells. PMID- 26133240 TI - A Mechanism-Based Model for the Prediction of the Metabolic Sites of Steroids Mediated by Cytochrome P450 3A4. AB - Early prediction of xenobiotic metabolism is essential for drug discovery and development. As the most important human drug-metabolizing enzyme, cytochrome P450 3A4 has a large active cavity and metabolizes a broad spectrum of substrates. The poor substrate specificity of CYP3A4 makes it a huge challenge to predict the metabolic site(s) on its substrates. This study aimed to develop a mechanism-based prediction model based on two key parameters, including the binding conformation and the reaction activity of ligands, which could reveal the process of real metabolic reaction(s) and the site(s) of modification. The newly established model was applied to predict the metabolic site(s) of steroids; a class of CYP3A4-preferred substrates. 38 steroids and 12 non-steroids were randomly divided into training and test sets. Two major metabolic reactions, including aliphatic hydroxylation and N-dealkylation, were involved in this study. At least one of the top three predicted metabolic sites was validated by the experimental data. The overall accuracy for the training and test were 82.14% and 86.36%, respectively. In summary, a mechanism-based prediction model was established for the first time, which could be used to predict the metabolic site(s) of CYP3A4 on steroids with high predictive accuracy. PMID- 26133241 TI - Homo-FRET Based Biosensors and Their Application to Multiplexed Imaging of Signalling Events in Live Cells. AB - Multiplexed imaging of Forster Resonance Energy Transfer (FRET)-based biosensors potentially presents a powerful approach to monitoring the spatio-temporal correlation of signalling pathways within a single live cell. Here, we discuss the potential of homo-FRET based biosensors to facilitate multiplexed imaging. We demonstrate that the homo-FRET between pleckstrin homology domains of Akt (Akt PH) labelled with mCherry may be used to monitor 3'-phosphoinositide accumulation in live cells and show how global analysis of time resolved fluorescence anisotropy measurements can be used to quantify this accumulation. We further present multiplexed imaging readouts of calcium concentration, using fluorescence lifetime measurements of TN-L15-a CFP/YFP based hetero-FRET calcium biosensor with 3'-phosphoinositide accumulation. PMID- 26133242 TI - Lack of Globulin Synthesis during Seed Development Alters Accumulation of Seed Storage Proteins in Rice. AB - The major seed storage proteins (SSPs) in rice seeds have been classified into three types, glutelins, prolamins, and globulin, and the proportion of each SSP varies. It has been shown in rice mutants that when either glutelins or prolamins are defective, the expression of another type of SSP is promoted to counterbalance the deficit. However, we observed reduced abundances of glutelins and prolamins in dry seeds of a globulin-deficient rice mutant (Glb-RNAi), which was generated with RNA interference (RNAi)-induced suppression of globulin expression. The expression of the prolamin and glutelin subfamily genes was reduced in the immature seeds of Glb-RNAi lines compared with those in wild type. A proteomic analysis of Glb-RNAi seeds showed that the reductions in glutelin and prolamin were conserved at the protein level. The decreased pattern in glutelin was also significant in the presence of a reductant, suggesting that the polymerization of the glutelin proteins via intramolecular disulfide bonds could be interrupted in Glb-RNAi seeds. We also observed aberrant and loosely packed structures in the storage organelles of Glb-RNAi seeds, which may be attributable to the reductions in SSPs. In this study, we evaluated the role of rice globulin in seed development, showing that a deficiency in globulin could comprehensively reduce the expression of other SSPs. PMID- 26133243 TI - Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure. AB - The biological effects of low-dose ionizing radiation (LDIR) exposure in humans are not comprehensively understood, generating a high degree of controversy in published literature. The earliest stages of human development are known to be among the most sensitive to stress exposures, especially genotoxic stresses. However, the risks stemming from exposure to LDIR, particularly within the clinical diagnostic relevant dose range, have not been directly evaluated in human embryonic stem cells (hESCs). Here, we describe the dynamics of the whole genome transcriptional responses of different hESC lines to both LDIR and, as a reference, high-dose IR (HDIR). We found that even doses as low as 0.05 Gy could trigger statistically significant transient changes in a rather limited subset of genes in all hESCs lines examined. Gene expression signatures of hESCs exposed to IR appear to be highly dose-, time-, and cell line-dependent. We identified 50 genes constituting consensus gene expression signature as an early response to HDIR across all lines of hESC examined. We observed substantial differences in biological pathways affected by either LDIR or HDIR in hESCs, suggesting that the molecular mechanisms underpinning the responses of hESC may fundamentally differ depending on radiation doses. PMID- 26133244 TI - Identification of miRNAs and Their Targets in Cotton Inoculated with Verticillium dahliae by High-Throughput Sequencing and Degradome Analysis. AB - MicroRNAs (miRNAs) are a group of endogenous small non-coding RNAs that play important roles in plant growth, development, and stress response processes. Verticillium wilt is a vascular disease in plants mainly caused by Verticillium dahliae Kleb., the soil-borne fungal pathogen. However, the role of miRNAs in the regulation of Verticillium defense responses is mostly unknown. This study aimed to identify new miRNAs and their potential targets that are involved in the regulation of Verticillium defense responses. Four small RNA libraries and two degradome libraries from mock-infected and infected roots of cotton (both Gossypium hirsutum L. and Gossypium barbadense L.) were constructed for deep sequencing. A total of 140 known miRNAs and 58 novel miRNAs were identified. Among the identified miRNAs, many were differentially expressed between libraries. Degradome analysis showed that a total of 83 and 24 genes were the targets of 31 known and 14 novel miRNA families, respectively. Gene Ontology analysis indicated that many of the identified miRNA targets may function in controlling root development and the regulation of Verticillium defense responses in cotton. Our findings provide an overview of potential miRNAs involved in the regulation of Verticillium defense responses in cotton and the interactions between miRNAs and their corresponding targets. The profiling of these miRNAs lays the foundation for further understanding of the function of small RNAs in regulating plant response to fungal infection and Verticillium wilt in particular. PMID- 26133245 TI - A New Oviraptorid Dinosaur (Dinosauria: Oviraptorosauria) from the Late Cretaceous of Southern China and Its Paleobiogeographical Implications. AB - The Ganzhou area of Jiangxi Province, southern China is becoming one of the most productive oviraptorosaurian localities in the world. A new oviraptorid dinosaur was unearthed from the uppermost Upper Cretaceous Nanxiong Formation of Ganzhou area. It is characterized by an anterodorsally sloping occiput and quadrate (a feature shared with Citipati), a circular supratemporal fenestra that is much smaller than the lower temporal fenestra, and a dentary in which the dorsal margin above the external mandibular fenestra is strongly concave ventrally. The position of the anteroventral corner of the external naris in relation to the posterodorsal corner of the antorbital fenestra provides new insight into the craniofacial evolution of oviraptorosaurid dinosaurs. A phylogenetic analysis recovers the new taxon as closely related to the Mongolian Citipati. Six oviraptorid dinosaurs from the Nanxiong Formation (Ganzhou and Nanxiong) are distributed within three clades of the family. Each of the three clades from the Nanxiong Formation has close relatives in Inner Mongolia and Mongolia, and in both places each clade may have had a specific diet or occupied a different ecological niche. Oviraptorid dinosaurs were geographically widespread across Asia in the latest Cretaceous and were an important component of terrestrial ecosystems during this time. PMID- 26133246 TI - 5-Azacitidine induces demethylation of PTPL1 and inhibits growth in non-Hodgkin lymphoma. AB - Non-Hodgkin lymphoma (NHL) consists of various lymphoid malignancies with a diverse clinical pathology and biological characteristics. Methylation of cytosine residues by DNA methyltransferases at CpG dinucleotides in the promoter region of the genes is a major epigenetic modification in mammalian genomes that can have profound effects on gene expression. The PTPL1 methylation pattern was screened by methylation-specific polymerase chain reaction (MSP) in 7 lymphoma derived cell lines and in 47 samples of diffuse large B cell lymphoma (DLBCL). The PTPL1 gene was hypermethylated in the CA46, Raji, Jurkat and DB cell lines; however, it was unmethylated in the Hut78, Maver and Z138 cell lines. The expression of PTPL1 mRNA was re-inducible by 5-azacytidine (5-Aza), an agent of DNA demethylation. The methylations were detected in 59.6% of DLBCL versus 6.3% in reactive lymph node proliferation. Therefore, the present data showed that PTPL1 was epigenetically regulated in NHL suggesting an involvement of the PTPL1 tumor-suppressor genes in NHL, and highlights 5-Aza as a potential therapeutic candidate for NHL. PMID- 26133247 TI - Pathology of Internal Limiting Membrane Specimens Following Intravitreal Injection of Ocriplasmin. AB - PURPOSE: To describe ultrastructure and immunocytochemistry of internal limiting membrane peelings after unsuccessful treatment with ocriplasmin, to compare with untreated eyes, and to correlate with clinical imaging data. DESIGN: Interventional comparative case series. METHODS: Internal limiting membrane specimens were removed from 10 eyes with small macular holes and vitreomacular traction during vitrectomy after intravitreal ocriplasmin injection without release of traction or closure of macular holes during follow-up. Based on optical coherence tomography analysis, specimens from 10 other eyes without ocriplasmin treatment served as controls. All specimens were processed as flat mounts for phase-contrast microscopy followed by immunolabeling for fluorescence microscopy and embedding in epoxy resin with serial sectioning for transmission electron microscopy. RESULTS: Despite the absence of contractive epiretinal membranes on optical coherence tomography, we found epiretinal cells and vitreous collagen fibrils on the internal limiting membrane in specimens removed from eyes with and without previous pharmacologic vitreolysis. Immunolabeling revealed glial cells and hyalocytes in macular holes, whereas myofibroblasts were predominant in vitreomacular traction. There was no apparent damage of the vitreoretinal interface after unsuccessful pharmacologic vitreolysis compared to untreated controls. CONCLUSIONS: Epiretinal cell proliferation and vitreous collagen fibrils with close adhesions to the internal limiting membrane are not always detectable by optical coherence tomography or may not have been recognized. Since they are associated with unsuccessful ocriplasmin treatment, presence and topography of epiretinal cells and vitreous collagen remnants on the internal limiting membrane should be further elucidated in order to refine criteria and indications for case selection in pharmacologic vitreolysis. PMID- 26133248 TI - Effect of Topical Tacrolimus in the Treatment of Thygeson's Superficial Punctate Keratitis. AB - PURPOSE: To evaluate topical tacrolimus ointment for treating Thygeson's superficial punctate keratitis (Thygeson SPK). DESIGN: Retrospective interventional case series. METHODS: setting: Institutional practice. PATIENT POPULATION: The medical records of 14 patients (9 women; age range, 9-65 years) with Thygeson SPK were reviewed retrospectively. Diagnosis was based on the history and clinical examination. INTERVENTION: Patients were treated with tacrolimus 0.03% eye ointment instilled into the lower fornix twice daily for the first 2 weeks, followed by nocturnal application. The clinical signs and symptoms were assessed after 1 month of treatment. The drug was tapered with disease improvement. MAIN OUTCOME MEASURE(S): Treatment efficacy and side effects. RESULTS: All patients had bilateral disease (average duration, 6 years). All patients, except 2 who used the medication irregularly, had improved visual acuity (VA), symptoms, and signs as long as the medication was applied. Before treatment 28.57% of patients had VA between 20/30 and 20/50, with improvement after treatment to 20/25 or 20/20. Attempts to withdraw the medication resulted in recurrent disease, and, therefore, treatment was not curative during the study period. No significant local medication side effects were reported. CONCLUSION: Tacrolimus eye ointment 0.03% was effective for controlling Thygeson SPK for a long period with good patient tolerance and no noticeable local or systemic side effects. During the average 6-year follow-up, treatment was not curative. Randomized studies are difficult to conduct because of the disease rarity. PMID- 26133249 TI - Local Recurrence After Primary Proton Beam Therapy in Uveal Melanoma: Risk Factors, Retreatment Approaches, and Outcome. AB - PURPOSE: To evaluate the risk factors, recurrence rates, retreatments, and long term patient outcomes following proton beam therapy for uveal melanoma. DESIGN: Retrospective interventional case series. METHODS: All patients treated with primary proton beam therapy for uveal melanoma at the oncology service at Charite Berlin and Helmholtz-Zentrum-Berlin between May 1998 and December 2008 were reviewed for local recurrence. Of 982 patients, 982 eyes matched the inclusion criteria. The data were obtained from electronic health records, operative reports, discharge letters, and radiation planning. Comparisons of fundus photographs and ultrasound measurements were performed to assess the growth pattern of the tumor and to determine the success of retreatment, in the case that a globe-retaining therapy was undertaken. RESULTS: Of 982 patients, 35 patients (3.6%) developed local recurrence. The median follow-up was 60.7 months (6.0-170.4 months). Local control rate was 96.4% and the overall eye retention rate was 95.0% in this cohort. Local recurrence was correlated with a higher risk for metastasis and reduced survival. Largest tumor diameter was identified as the sole statistically significant risk factor for local recurrence (P = .00001). All globe-retaining retreatment approaches for local recurrence, including proton beam therapy, brachytherapy, and transpupillary thermotherapy used for recurrences at the tumor margins, showed good local tumor control and similar metastasis-free survivals. CONCLUSIONS: This study showed that each globe retaining retreatment approach can result in satisfying local tumor control. In case of early detection of local recurrence, preservation of the globe can be warranted. Therefore, regularly performed follow-ups should be ensured. PMID- 26133250 TI - Chronic central serous chorioretinopathy imaged by optical coherence tomographic angiography. AB - PURPOSE: To describe optical coherence tomographic (OCT) angiography findings in chronic central serous chorioretinopathy (CSC), and to characterize their OCT B scans by means of the split-spectrum amplitude-decorrelation angiography algorithm. DESIGN: Evaluation of an imaging technique in a cohort of patients. METHODS: Fluorescein (FA) and indocyanine green (ICGA) angiography (Heidelberg Spectralis, Heidelberg, Germany), OCT angiography, and OCT angiography with the split-spectrum amplitude-decorrelation angiography algorithm (XR Optovue, Fremont, California, USA) were performed. A qualitative analysis of the entire imaging data was done. RESULTS: Twelve eyes of 10 patients were included. Mean visual acuity was 20/30. All eyes presented findings consistent with chronic CSC (lasting more than 6 months) on biomicroscopic examination, autofluorescence, FA, ICGA, and OCT. ICGA showed the characteristic choroidal hyperpermeability, while there was no evidence of choroidal neovascularization (CNV). OCT B-scans showed 2 distinct profiles of the retinal pigment epithelium (RPE): a slight RPE detachment with small undulations was evident in 7 of 12 eyes, while 5 eyes presented a flat RPE profile. OCT angiography in 7 eyes (58%) revealed the presence of a distinct CNV corresponding to the ICGA hyperpermeability. The qualitative analysis of the OCT B-scans compared to the OCT angiographic images demonstrated that the CNV corresponded to the small undulations within the slight RPE detachment, confirming its vascularized nature. On the contrary, OCT angiography showed a normal choroidal circulation in the remaining 5 eyes (42%) with a flat RPE profile. CONCLUSIONS: OCT angiography allows detection of CNV in chronic CSC not visible with other imaging techniques. CNV corresponds to the small undulating RPE detachment on B-scan. This might allow an appropriate treatment resulting in a better visual outcome. PMID- 26133251 TI - Functional Defects in Color Vision in Patients With Choroideremia. AB - PURPOSE: To characterize defects in color vision in patients with choroideremia. DESIGN: Prospective cohort study. METHODS: Thirty patients with choroideremia (41 eyes) and 10 age-matched male controls (19 eyes) with visual acuity of >=6/36 attending outpatient clinics in Oxford Eye Hospital underwent color vision testing with the Farnsworth-Munsell 100 hue test, visual acuity testing, and autofluorescence imaging. To exclude changes caused by degeneration of the fovea, a subgroup of 14 patients with a visual acuity >=6/6 was analyzed. Calculated color vision total error scores were compared between the groups and related to a range of factors using a random-effects model. RESULTS: Mean color vision total error scores were 120 (95% confidence interval [CI] 92, 156) in the >=6/6 choroideremia group, 206 (95% CI 161, 266) in the <6/6 visual acuity choroideremia group, and 47 (95% CI 32, 69) in the control group. Covariate analysis showed a significant difference in color vision total error score between the groups (P < .001 between each group). CONCLUSIONS: Patients with choroideremia have a functional defect in color vision compared with age-matched controls. The color vision defect deteriorates as the degeneration encroaches on the fovea. The presence of an early functional defect in color vision provides a useful biomarker against which to assess successful gene transfer in gene therapy trials. PMID- 26133252 TI - Sequestrated lumbar disc fragment mimicking ventral epidural abscess. PMID- 26133253 TI - Intramedullary pilocytic astrocytoma. PMID- 26133254 TI - Conservative treatment for Landells and Van Peteghem type II atlas fracture accompanied with atlantoaxial rotatory subluxation. PMID- 26133255 TI - Does provocative discography cause clinically important injury to the lumbar intervertebral disc? A 10-year matched cohort study. AB - BACKGROUND CONTEXT: Provocative discography, an invasive diagnostic procedure involving disc puncture with pressurization, is a test for presumptive discogenic pain in the lumbar spine. The clinical validity of this test is unproven. Data from multiple animal studies confirm that disc puncture causes early disc degeneration. A recent study identified radiographic disc degeneration on magnetic resonance imaging (MRI) performed 10 years later in human subjects exposed to provocative discography. The clinical effect of this disc degeneration after provocative discography is unknown. PURPOSE: The aim of this study was to investigate the clinical effects of lumbar provocative discography on patients subjected to this evaluation method. STUDY DESIGN/SETTING: A prospective, 10-year matched cohort study. PATIENT SAMPLE: Subjects (n=75) without current low back pain (LBP) problems were recruited to participate in a study of provocative discography at the L3-S1 discs. A closely matched control cohort was simultaneously recruited to undergo a similar evaluation except for discography injections. OUTCOME MEASURES: The primary outcome variables were diagnostic imaging events and lumbar disc surgery events. The secondary outcome variables were serious LBP events, disability events, and medical visits. METHODS: The discography subjects and control subjects were followed by serial protocol evaluations at 1, 2, 5, and 10 years after enrollment. The lumbar disc surgery events and diagnostic imaging (computed tomography (CT) or MRI) events were recorded. In addition, the interval and cumulative lumbar spine events were recorded. RESULTS: Of the 150 subjects enrolled, 71 discography subjects and 72 control subjects completed the baseline evaluation. At 10-year follow-up, 57 discography and 53 control subjects completed all interval surveillance evaluations. There were 16 lumbar surgeries in the discography group, compared with four in the control group. Medical visits, CT/MRI examinations, work loss, and prolonged back pain episodes were all more frequent in the discography group compared with control subjects. CONCLUSION: The disc puncture and pressurized injection performed during provocative discography can increase the risk of clinical disc problems in exposed patients. PMID- 26133256 TI - The distribution of bone mass in the lumbar vertebrae: are we measuring the right target? AB - BACKGROUND CONTEXT: The ideal target of bone mineral density (BMD) measurements of the spine is the trabecula-rich vertebral body. Yet, spine BMD measurements routinely obtained with dual-energy X-ray absorptiometry also include the posterior elements of the vertebra, which are mainly cortical bone and insensitive to bone loss. PURPOSE: We compared the bone mass of the vertebral body and posterior elements to determine the contributions of vertebral components to vertebral BMD measurements. STUDY DESIGN: A micro-computed tomography study of lumbar vertebral bone. METHODS: From a spine archive, 144 cadaveric lumbar vertebrae (L1-L5) from 48 male human spines (mean age, 50 years) were scanned in air using micro-computed tomography to measure bone volume, bone mineral content (BMC) and BMD of the vertebral body, posterior elements, and entire vertebra. The contributions of the vertebral components to the total vertebral BMC and volume were compared, and the correlations between the BMC and BMD of the vertebrae and their components were examined. RESULTS: Overall, the vertebral body contributed about one-third of the total vertebral BMC and two thirds of the total vertebral volume, and the posterior elements contributed the remainder. The vertebral body BMC and BMD were poorly correlated to those of the posterior elements (r=0.39 for BMC and r=0.34 for BMD, p<.0001) and moderately correlated to the whole vertebra (r=0.77 and 0.75, respectively, p<.0001). The BMC and BMD of the posterior elements and whole vertebra were more strongly correlated (r=0.89 and 0.84, respectively, p<.0001). CONCLUSIONS: The posterior elements are the primary contributor to vertebral BMC and BMD measurements. Dual energy X-ray absorptiometry spine BMD measurements are likely to be more representative of the posterior elements than the targeted vertebral body. The findings elucidate the extent of the limitation of dual-energy X-ray absorptiometry spine BMD measurements. PMID- 26133257 TI - A rare case of sarcoma involving atlas. PMID- 26133258 TI - Phenotype profiling of Modic changes of the lumbar spine and its association with other MRI phenotypes: a large-scale population-based study. AB - BACKGROUND CONTEXT: Modic changes (MC) are associated with low back pain. They represent vertebral endplate and adjacent vertebral marrow changes on magnetic resonance imaging (MRI), classified into three types. Because of small sample sizes, patient cohorts, and limited phenotype assessment, the morphology and involvement of MC and their association with other spinal phenotypes remain speculative. PURPOSE: We addressed and proposed a phenotypic profiling of MC and their relationship with lumbar MRI phenotypes in a large-scale population-based study. STUDY DESIGN/SETTING: A cross-sectional study of the Hong Kong Disc Degeneration Cohort. PATIENT SAMPLE: The study population consisted of 1,546 Southern Chinese volunteers. OUTCOME MEASURES: Topographical and morphological dimensions of MC, presence of disc degeneration (DD) and displacement, and Schmorl nodes were evaluated. METHODS: Axial T1-weighted and sagittal T2-weighted MRIs (3T) were assessed. RESULTS: Females were 62.4% (mean age, 49 years). The overall prevalence of MC was 21.9% (6.3% Type I and 15.5% Type II). Of all MC, 76% were located at the two lowest lumbar levels. Modic changes at the two lowest lumbar levels were more commonly located laterally (p<.001), less commonly anteriorly (p<.001), and were more extensive horizontally (p=.006) but not in vertical height compared with the upper levels. Type I MC were less common in the anterior part (p=.022), larger in size (height p=.004), and affected more likely the whole horizontal plane (p=.016) than Type II MC. Modic changes were associated with disc displacement, Schmorl nodes, and DD at the affected level (all p<.001), and the strength of association increased with the size of the lesion. Type I MC were associated more strongly with disc displacement (p=.008) and DD (p=.022) than Type II MC. CONCLUSIONS: Our large-scale MRI study is the first to definitely note that MC were size- and type-dependently significantly associated with disc pathology and endplate abnormalities. Our phenotype profiling of MC may have clinical utility. PMID- 26133259 TI - Epidemiology of atlas fractures--a national registry-based cohort study of 1,537 cases. AB - BACKGROUND CONTEXT: The epidemiology of fractures of the first cervical vertebra the atlas-has not been well documented. Previous studies concerning atlas fractures focus on treatment and form a weak platform for epidemiologic study. PURPOSE: This study aims to provide reliable epidemiologic data on atlas fractures. STUDY DESIGN: This was a national registry-based cohort study. PATIENT SAMPLE: A total of 1,537 cases of atlas fractures between 1997 and 2011 from the Swedish National Patient Registry (NPR). OUTCOME MEASURES: The outcome measures were annual incidence and mortality. METHODS: Data from the NPR and the Swedish Cause of Death Registry were extracted, including age, gender, diagnosis, comorbidity, treatment codes, and date of death. The Charlson Comorbidity Index was calculated and a survival analysis performed. RESULTS: A total of 869 (56.5%) cases were men, and 668 (43.5%) were women. The mean age of the entire population was 64 years. The proportion of atlas fractures of all registered cervical fractures was 10.6%. In 19% of all cases, there was an additional fracture of the axis, and 7% of all cases had additional subaxial cervical fractures. Patients with fractures of the axis were older than patients with isolated atlas fractures. The annual incidence almost doubled during the study period, and in 2011, it was 17 per million inhabitants. The greatest increase in incidence occurred in the elderly population. CONCLUSIONS: Atlas fractures occurred predominantly in the elderly population. Further study is needed to determine the cause of the increasing incidence. PMID- 26133260 TI - A cornucopia of screening and diagnostic techniques for human papillomavirus associated cervical carcinomas. AB - Cervical carcinoma is one of the major consequences of human papillomavirus (HPV) infections. Although HPV infections of cervix do not always progress to cancer, 90% cases of cervical cancer have been found associated with high risk HPV (hrHPV) infection. Usually, HPV infection is asymptomatic; however, this asymptomatic infection can cause abnormal changes in cervix ultimately leading to cancer development. These changes can be detected by the application of screening tests at regular time intervals. For this purpose, morphological, cytological, and DNA based techniques are available. Nevertheless, abnormal screening tests have only the predictive value for precancerous lesions and thus require further evaluation which is usually done by using diagnostic techniques. So far, colposcopy and histological examination alone were considered as the gold standards for cervical cancer diagnosis. Currently, some tests based on expression level of host cell biomarkers are also being used along with histology for diagnostic purpose. Albeit, these tests have significant specificity and sensitivity values but they are unable to suggest a particular viral genotype involved in infection. Diagnostic methods such as PCR, HPV genotyping assays, microarray, and mRNA based assays are useful to predict the genotypes as well as the quantity of viral load in a host cell. Similarly, these diagnostic procedures have high specificity and sensitivity ranges. However, only few of them are practiced commonly, as approval of these tests as routine diagnostic tests requires clinical validation and cost effectiveness. PMID- 26133268 TI - Inhibition of growth and migration of oral and cervical cancer cells by citrus polyphenol. AB - BACKGROUND/PURPOSE: It has been confirmed that polyphenolic compounds present in food have various pharmaceutical functions. The purpose of this study was to evaluate citrus polyphenol (CP) for dental applications. The culture medium with CP was developed to inhibit the proliferation of oral cancer cells. CP could be used as a supplemental compound for topical application for oral cancer patients. METHODS: In this study, the metabolic activity and cell toxicity of CP (at concentrations of 1%, 0.1%, and 0.01%) for oral and cervical cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays (n = 6). Furthermore, the effects of CP on motilities of oral and cervical cancer cells were also evaluated using a scratch assay model. RESULTS: We found that the growth of Ca9-22 and HeLa cells on tissue culture polystyrene was greatly inhibited when 1% CP was added to the medium. In addition, significant differences (p < 0.01) in cytotoxicities of oral and cervical cancer cells were observed after 6 days in the culture medium to which 1% CP was added. Furthermore, using a scratch assay model to evaluate the migratory abilities of oral and cervical cancer cells, it was also found that CP could inhibit the migratory abilities of cancer cells. CONCLUSION: The results confirmed the feasibility of the topical application of CP as a supplemental compound for inhibition of cancer cell proliferation and migration. PMID- 26133261 TI - Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms. AB - NADPH oxidases (Nox) represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS). Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases. PMID- 26133262 TI - Herbal formula, Scutellariae radix and Rhei rhizoma attenuate dimethylnitrosamine induced liver fibrosis in a rat model. AB - The bioactive components extracted from Scutellariae radix and Rhei rhizoma (SR) have been commonly used to treat liver diseases. The aim of this study was to verify the underlying mechanisms and antifibrotic effects of ethanol extract from the herbal combinatorial formula (SRE) in a dimethylnitrosamine (DMN) administered rat model, with functional proteome tools. Our results indicated that the hepatic collagen content and alpha-smooth muscle actin expression were obviously alleviated by treatment with SRE. Comprehensive proteomics revealed global protein changes, and the network analysis implied that SRE application would attenuate oxidative stress and cytoskeleton dysregulation caused by DMN exposure. Next, marked downregulation of antioxidant enzymes mediated by DMN treatment was restored in the presence of SRE, while SRE treatment contributed to decreased MDA content. Moreover, protein carbonylation and DNA adduction induced by oxidative stress finally leading to liver injury were also reduced under SRE administration. These findings demonstrate that SRE could effectively prevent hepatic fibrosis mainly through regulating the redox status, and subsequently modulating the modification of intracellular molecules. Our experiments might help in developing novel therapeutic strategies against oxidation-caused liver diseases. PMID- 26133269 TI - Diffusion-mediated dephasing in the dipole field around a single spherical magnetic object. AB - In this work, the time evolution of the free induction decay caused by the local dipole field of a spherical magnetic perturber is analyzed. The complicated treatment of the diffusion process is replaced by the strong-collision approximation that allows a determination of the free induction decay in dependence of the underlying microscopic tissue parameters such as diffusion coefficient, sphere radius and susceptibility difference. The interplay between susceptibility- and diffusion-mediated effects yields several dephasing regimes of which, so far, only the classical regimes of motional narrowing and static dephasing for dominant and negligible diffusion, respectively, were extensively examined. Due to the asymmetric form of the dipole field for spherical objects, the free induction decay exhibits a complex component in contradiction to the cylindrical case, where the symmetric local dipole field only causes a purely real induction decay. Knowledge of the shape of the corresponding frequency distribution is necessary for the evaluation of more sophisticated pulse sequences and a detailed understanding of the off-resonance distribution allows improved quantification of transverse relaxation. PMID- 26133270 TI - Determining the location and nearest neighbours of aluminium in zeolites with atom probe tomography. AB - Zeolite catalysis is determined by a combination of pore architecture and Bronsted acidity. As Bronsted acid sites are formed by the substitution of AlO4 for SiO4 tetrahedra, it is of utmost importance to have information on the number as well as the location and neighbouring sites of framework aluminium. Unfortunately, such detailed information has not yet been obtained, mainly due to the lack of suitable characterization methods. Here we report, using the powerful atomic-scale analysis technique known as atom probe tomography, the quantitative spatial distribution of individual aluminium atoms, including their three dimensional extent of segregation. Using a nearest-neighbour statistical analysis, we precisely determine the short-range distribution of aluminium over the different T-sites and determine the most probable Al-Al neighbouring distance within parent and steamed ZSM-5 crystals, as well as assess the long-range redistribution of aluminium upon zeolite steaming. PMID- 26133271 TI - High expression of transforming acidic coiled coil-containing protein 3 strongly correlates with aggressive characteristics and poor prognosis of gastric cancer. AB - Transforming acidic coiled coil-containing protein 3 (TACC3) is well understood to regulate mitotic spindle dynamics and centrosome integrity during mitosis. TACC3 has been suggested to be deregulated in a variety of human malignancies and may be involved in the process of cancer progression. The aim of the present study was to determine the status of TACC3 expression in gastric cancer (GC) and to clarify its clinical/prognostic significance. In the present study, we applied quantitative PCR (qPCR) and western blotting to examine TACC3 mRNA/protein expression in paired GC tissues and matched adjacent non-malignant tissues. Immunohistochemistry (IHC) was performed on a large cohort of 186 postoperative GC samples. Chi-square test, Kaplan-Meier analysis and Cox regression modelling were used to analyse the data. Upregulated mRNA and protein expression levels of TACC3 were observed in the majority of the GC tissues based on qPCR and western blotting compared to the adjacent non-cancerous gastric tissues. Specific IHC staining for TACC3 was predominantly identified in the cytoplasm of the cancer cells. A high expression of TACC3 was detected in 102 of the 186 (54.8%) tissue samples and was significantly associated with the extracapsular extension of the tumour (P<0.001), tumour relapse (P<0.001) and shortened overall survival in GC (P<0.001). Further analysis demonstrated that the TACC3 expression level stratified the patient outcome in stage II (P=0.040), stage III (P<0.001), T3/4 (P<0.001), N positive (P<0.001) and poorly differentiated/undifferentiated tumour subgroups (P<0.001). The Cox regression analysis suggested that a high expression of TACC3 was an independent prognostic factor for GC patients. The measurement of TACC3 protein expression may be beneficial for predicting clinical outcomes for GC patients. PMID- 26133272 TI - Domestic estimated breeding values and genomic enhanced breeding values of bulls in comparison with their foreign genomic enhanced breeding values. AB - Estimated breeding values (EBVs) and genomic enhanced breeding values (GEBVs) for milk production of young genotyped Holstein bulls were predicted using a conventional BLUP - Animal Model, a method fitting regression coefficients for loci (RRBLUP), a method utilizing the realized genomic relationship matrix (GBLUP), by a single-step procedure (ssGBLUP) and by a one-step blending procedure. Information sources for prediction were the nation-wide database of domestic Czech production records in the first lactation combined with deregressed proofs (DRP) from Interbull files (August 2013) and domestic test-day (TD) records for the first three lactations. Data from 2627 genotyped bulls were used, of which 2189 were already proven under domestic conditions. Analyses were run that used Interbull values for genotyped bulls only or that used Interbull values for all available sires. Resultant predictions were compared with GEBV of 96 young foreign bulls evaluated abroad and whose proofs were from Interbull method GMACE (August 2013) on the Czech scale. Correlations of predictions with GMACE values of foreign bulls ranged from 0.33 to 0.75. Combining domestic data with Interbull EBVs improved prediction of both EBV and GEBV. Predictions by Animal Model (traditional EBV) using only domestic first lactation records and GMACE values were correlated by only 0.33. Combining the nation-wide domestic database with all available DRP for genotyped and un-genotyped sires from Interbull resulted in an EBV correlation of 0.60, compared with 0.47 when only Interbull data were used. In all cases, GEBVs had higher correlations than traditional EBVs, and the highest correlations were for predictions from the ssGBLUP procedure using combined data (0.75), or with all available DRP from Interbull records only (one-step blending approach, 0.69). The ssGBLUP predictions using the first three domestic lactation records in the TD model were correlated with GMACE predictions by 0.69, 0.64 and 0.61 for milk yield, protein yield and fat yield, respectively. PMID- 26133273 TI - Defining Subthreshold PTSD in the DSM-IV Literature: A Look Toward DSM-5. AB - Subthreshold posttraumatic stress disorder (PTSD), whether due to absence of symptom development or partial remission, is the subject of research and clinical work despite being absent from the DSM. A problem with the literature is that subthreshold definitions are inconsistent across studies and therefore aggregating results is difficult. This study compared the diagnostic hit rates and validity of commonly used definitions of Subthreshold PTSD in a single sample. Three definitions of Subthreshold PTSD were extracted from the literature and two were formed, including a model of DSM-5 PTSD-criterion sets, and a definition that requires six or more PTSD symptoms, but no particular criterion set. Participants (N = 654) with a criterion A stressor, but without full PTSD diagnosis, were included. Most individuals did not meet any definition of Subthreshold PTSD. Findings are discussed in light of previous research and need for increased understanding of the diagnostic implications of Subthreshold PTSD. PMID- 26133274 TI - The Practice of Holy Fasting in the Late Middle Ages: A Psychiatric Approach. AB - During the Late Middle Ages, the practice of fasting among religious women in an attempt to follow a pious and ascetic life was common. In this paper, three cases of medieval religious women are described with a particular attention to the figure of St. Catherine of Siena, her life, popularity, and iconography. In the Middle Ages, holy fasting was characterized by a refusal to eat that could involve binging and purging, lack of menstruation, an interest in cooking for others, and in some cases death due to inanition. In the Medieval narratives of fasting holy women, we can see patterns that are compatible with symptoms of anorexia nervosa. From a psychiatric perspective, it is possible to elucidate and understand the practice of fasting among religious people in the Late Middle Ages. PMID- 26133275 TI - Nonallelic homologous recombination of the FCGR2/3 locus results in copy number variation and novel chimeric FCGR2 genes with aberrant functional expression. AB - The human FCGR2/3 locus, containing five highly homologous genes encoding the major IgG receptors, shows extensive copy number variation (CNV) associated with susceptibility to autoimmune diseases. Having genotyped >4000 individuals, we show that all CNV at this locus can be explained by nonallelic homologous recombination (NAHR) of the two paralogous repeats that constitute the majority of the locus, and describe four distinct CNV regions (CNRs) with a highly variable prevalence in the population. Apart from CNV, NAHR events also created several hitherto unidentified chimeric FCGR2 genes. These include an FCGR2A/2C chimeric gene that causes a decreased expression of FcgammaRIIa on phagocytes, resulting in a decreased production of reactive oxygen species in response to immune complexes, compared with wild-type FCGR2A. Conversely, FCGR2C/2A chimeric genes were identified to lead to an increased expression of FCGR2C. Finally, a rare FCGR2B null-variant allele was found, in which a polymorphic stop codon of FCGR2C is introduced into one FCGR2B gene, resulting in a 50% reduction in protein expression. Our study on CNRs and the chimeric genes is essential for the correct interpretation of association studies on FCGR genes as a determinant for disease susceptibility, and may explain some as yet unidentified extreme phenotypes of immune-mediated disease. PMID- 26133276 TI - Anatase TiO2 ultrathin nanobelts derived from room-temperature-synthesized titanates for fast and safe lithium storage. AB - Lithium-ion batteries (LIBs) are promising energy storage devices for portable electronics, electric vehicles, and power-grid applications. It is highly desirable yet challenging to develop a simple and scalable method for constructions of sustainable materials for fast and safe LIBs. Herein, we exploit a novel and scalable route to synthesize ultrathin nanobelts of anatase TiO2, which is resource abundant and is eligible for safe anodes in LIBs. The achieved ultrathin nanobelts demonstrate outstanding performances for lithium storage because of the unique nanoarchitecture and appropriate composition. Unlike conventional alkali-hydrothermal approaches to hydrogen titanates, the present room temperature alkaline-free wet chemistry strategy guarantees the ultrathin thickness for the resultant titanate nanobelts. The anatase TiO2 ultrathin nanobelts were achieved simply by a subsequent calcination in air. The synthesis route is convenient for metal decoration and also for fabricating thin films of one/three dimensional arrays on various substrates at low temperatures, in absence of any seed layers. PMID- 26133277 TI - Mechanically durable, superomniphobic coatings prepared by layer-by-layer technique for self-cleaning and anti-smudge. AB - Superomniphobic surfaces are of interest for anti-fouling, self-cleaning, anti smudge and low-drag applications. Many bioinspired surfaces developed previously are of limited use due to a lack of mechanical durability. From a previously developed technique, an adapted layer-by-layer approach involving charged species with electrostatic interactions between layers is combined with an uncharged fluorosilane layer to result in a durable, superomniphobic coating. This technique can provide the flexibility needed to improve adhesion to the substrate with the addition of a low surface tension coating at the air interface. In this work, polyelectrolyte binder, SiO2 nanoparticles, and fluorosilane layers are deposited, providing the combination of surface roughness and low surface tension to result in a superomniphobic coating with droplets of liquids with surface tensions from 72 to 21 mN m(-1) displaying contact angles exceeding 155 degrees with low tilt angles. The durability of these coatings was examined through the use of micro- and macrowear experiments. These coatings currently display levels of transparency acceptable for automotive applications. Fabrication via this novel combination of techniques results in durable, superomniphobic coatings displaying improved performance compared to existing work where either the durability or the repellency is compromised. PMID- 26133278 TI - Up-scaling the synthesis of Cu2O submicron particles with controlled morphologies for solar H2 evolution from water. AB - The synthesis of Cu2O was studied to examine the effects of up-scaling on the size and morphology of the resultant particles. As a result, a successful protocol employing an automated laboratory reactor was developed for large-scale synthesis of phase-pure Cu2O colloids with specific sizes in the submicron to micrometer range (0.2-2.6 MUm). The as-synthesized products have been studied by means of powder X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, UV-Vis-NIR spectroscopy, scanning electron microscopy, and photoelectrochemical measurements. A broad range of morphologies, both equilibrium (stellated octahedrons, cubes, cuboctahedrons, truncated octahedrons, truncated cuboctahedrons) and metastable (cage-like hierarchical structures, microspheres with flower-like texture), with uniform sizes have been selectively prepared either by careful tuning of synthesis conditions. Recrystallization of primary aggregates through Ostwald ripening is proposed as the formation mechanism for these Cu2O structures. As a photocathode for photoelectrochemical H2 evolution, Cu2O submicron cubes with exposed {001} facets exhibit a high open circuit potential of ca. 0.9 V vs. the RHE at pH 1. PMID- 26133279 TI - Anesthesia outside the operating room. PMID- 26133280 TI - Sedative medications outside the operating room and the pharmacology of sedatives. AB - PURPOSE OF REVIEW: There is a growing medical demand for suitable sedatives and analgesics to support the ongoing progress in diagnostic procedures and imaging techniques. This review provides an update of the pharmacology of the most commonly used drugs used for these procedures and shortly mention new drugs on the horizon. RECENT FINDINGS: There are many drugs available for procedural sedation; however, they all have drawbacks and shortcomings. Multiple adverse effects are associated with the use of these agents, hence monitoring is essential, and emergency equipment should be readily available. Newer drugs are on the horizon (e.g., remimazolam, fospropofol, and etomidate analogues) with a theoretical more predictable onset and offset; whether these will revolutionize the sedational practice sedation remains unknown. SUMMARY: Clinicians should be aware of the pharmacokinetic/pharmacodynamic differences of all agents in order to select appropriate medications for specific procedures and patients. PMID- 26133282 TI - Multi-view stereophotogrammetry for post-mastectomy breast reconstruction. AB - A multi-view three-dimensional stereophotogrammetry system was developed to capture 3D shape of breasts for breast cancer patients. The patients had received immediate unilateral breast reconstruction after mastectomy by the extended latissimus dorsi flap and without contralateral surgery. In order to capture the whole breast shape including the inframammary fold, the patients were introduced to the imaging room and leaned over the imaging rig to open up the inframammary fold and to expose the entire area of each breast. The imaging system consisted of eight high-resolution ([Formula: see text] pixels) digital cameras and four flash units. The cameras were arranged in four stereo pairs from four different view angles to cover the whole surface of the breasts. The system calibration was carried out ahead of every capture session, and the stereo images were matched to generate four range images to be integrated using an elastic model proposed. A watertight breast mesh model was reconstructed to measure the volume of the breast captured. The accuracy of using the developed multi-view stereophotogrammetry system for breast volume measurement was 11.12cc with SEM 7.74cc, comparing to the measurements of the water displacement method. It was concluded that the 3D stereophotogrammetry image system developed was more reliable than the method of water displacement. PMID- 26133283 TI - Building a three-dimensional model of the upper gastrointestinal tract for computer simulations of swallowing. AB - We aimed to provide realistic three-dimensional (3D) models to be used in numerical simulations of peristaltic flow in patients exhibiting difficulty in swallowing, also known as dysphagia. To this end, a 3D model of the upper gastrointestinal tract was built from the color cryosection images of the Visible Human Project dataset. Regional color heterogeneities were corrected by centering local histograms of the image difference between slices. A voxel-based model was generated by stacking contours from the color images. A triangle mesh was built, smoothed and simplified. Visualization tools were developed for browsing the model at different stages and for virtual endoscopy navigation. As result, a computer model of the esophagus and the stomach was obtained, mainly for modeling swallowing disorders. A central-axis curve was also obtained for virtual navigation and to replicate conditions relevant to swallowing disorders modeling. We show renderings of the model and discuss its use for simulating swallowing as a function of bolus rheological properties. The information obtained from simulation studies with our model could be useful for physicians in selecting the correct nutritional emulsions for patients with dysphagia. PMID- 26133285 TI - Pressure and electric field-induced metallization in the phase-engineered ZrX2 (X = S, Se, Te) bilayers. AB - The phase-, pressure- and electric field-induced changes in the electronic properties of Zr dichalcogenide, ZrX2 (X = S, Se, Te), bilayers are investigated using density functional theory. On going from the trigonal (T) to hexagonal (H) phase, a significant modulation in the electronic structure of bilayer dichalcogenides is predicted. This is mainly due to the distinct stacking nature of the bilayer in two phases leading to a delicate difference in the interplanar interaction, which is concurrently affected by the nature of X-X bonding. Application of the pressure reduces the band gap of layered dichalcogenides leading to the metallization of the ZrTe2 bilayer for ~6 GPa. Similarly, application of the transverse electric field (0.05-0.25 V A(-1)) induces a complete metallization in dichalcogenide bilayers. Our results show that band gap engineering by changing the phase, applying pressure and electric field can be an effective strategy to modulate the electronic properties of bilayer dichalcogenides for the next-generation device applications. PMID- 26133284 TI - Does left atrial appendage closure improve the success of pulmonary vein isolation? Results of a randomized clinical trial. AB - PURPOSE: The combination of left atrial appendage (LAA) occlusion with pulmonary vein isolation (PVI) potentially represents a comprehensive treatment for atrial fibrillation (AF), controlling symptoms while at the same time reducing the risk of stroke and the need for chronic anticoagulation. The aim of this randomized clinical trial was to assess the impact of LAA closure added to PVI in patients with high-risk AF. METHODS: Patients with a history of symptomatic paroxysmal or persistent AF refractory to >= 2 antiarrhythmic drugs, CHA2DS2-VASc score >= 2, and HAS-BLED score >= 3 were randomized to PVI-only (n = 44) or PVI with LAA closure (n = 45). RESULTS: Six patients in PVI + LAA closure group crossed over to PVI-only group due to failure of LAA closure device implantation. On-treatment comparisons at the 24 month follow-up revealed that 33 (66%) of the 50 PVI group and 23 (59%) of the 39 PVI with LAA closure group were AF-free on no antiarrhythmic drugs (p = 0.34). The PVI + LAA closure treatment was significantly associated with a higher AF burden during the blanking period: 9.7 +/- 10.8 vs 4.2 +/- 4.1% (p = 0.004). At the end follow-up, there were no serious complications and no strokes or thromboembolic events in either group. CONCLUSIONS: The combination of LAA closure device implantation with PVI was safe but was not observed to influence the success of PVI in patients with symptomatic refractory AF. Early AF after ablation, however, is increased by LAA closure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01695824. PMID- 26133286 TI - Self-assembly and crystallisation of indented colloids at a planar wall. AB - We report experimental and simulation studies of the structure of a monolayer of indented ("lock and key") colloids, on a planar surface. On adding a non absorbing polymer with prescribed radius and volume fraction, depletion interactions are induced between the colloids, with controlled range and strength. For spherical particles, this leads to crystallisation, but the indented colloids crystallise less easily than spheres, in both simulation and experiment. Nevertheless, simulations show that indented colloids do form plastic (rotator) crystals. We discuss the conditions under which this occurs, and the possibilities of lower-symmetry crystal states. We also comment on the kinetic accessibility of these states. PMID- 26133287 TI - Early history of scapular fractures. AB - The first to use the term Scapula was Vesalius (1514-1564) and thus it has remained ever since. Probably the oldest injured scapula, from 250 million years ago, was described by Chinese authors of a skeletal examination of a fossilised remains of a dinosaur Yangchuanosaurus hepingensis. In humans, the oldest known scapular fractures date back to the prehistoric and early historic times. In ancient times, a fracture of acromion was described in the treatises of Hippocrates. Early modern history of the treatment of scapular fractures is closely interlinked with the history of the French surgery. The first to point out the existence of these fractures were Petit, Du Verney and Desault in the 18th century. The first study devoted solely to scapular fractures was published by Traugott Karl August Vogt in 1799. Thomas Callaway published in 1849 an extensive dissertation on injuries to the shoulder girdle, in which he discussed a number of cases known at that time. The first radiograph of a scapular fracture was published by Petty in 1907. Mayo Robson (1884), Lambotte (1913) and Lane (1914) were pioneers in the surgical treatment of these fractures, followed in 1923 by the French surgeons Lenormat, Dujarrier and Basset. The first internal fixation of the glenoid fossa, including a radiograph, was published by Fischer in 1939. PMID- 26133288 TI - Infrared assessment of knee instability in ACL deficient patients. AB - PURPOSE: Previous clinical studies have shown that anterior cruciate ligament (ACL) ruptures require reconstructive surgery. The main goal of this study is an objective test definition for unstable knee diagnosis based on real measurements by using infrared cameras and adequate software. METHODS: In the study of gait analysis 35 males with deficient ACL's participated. Pathological parameters for anterior posterior translation (APT) and internal external rotation (IER) and their values of kinematic data were obtained from a gait analysis 3D system. Movement curves were obtained by recording the position of fluorescent markers over time. A machine learning algorithm was developed in order to support decisions on the severity of the ACL injury and its corresponding deficiency. The algorithm was based on logistic regression. RESULTS: The value of APT, designated as exponentiation of the ? coefficient (Exp (?)) of APT, showed that the likelihood of ACL-deficient knee occurrence due to higher values of APT is 1.1758 (95 % CI) times more frequent than that of the patients with lower values of APT. The value of IER, designated as Exp (?) of IER, showed that the patients with higher values of IER present 2.2516 (95 % CI) times higher values of ACL deficient knee frequency than those with lower values. CONCLUSION: This study showed that the creation of ordered pairs of pathological parameters gives a wider picture of ACL deficiency and that such an algorithm may improve both examination and treatment of patients. PMID- 26133289 TI - Intra-operative gaps affect outcome and postoperative kinematics in vivo following cruciate-retaining total knee arthroplasty. AB - PURPOSE: The following investigation evaluates the effect of intra-operative gaps after posterior cruciate ligament-retaining total knee arthroplasty using two dimensional/three-dimensional registration and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). METHODS: Patients were divided into two groups according to their 90 degrees -0 degrees component gap changes using a device designed by our laboratory. The wide gap group was defined as more than 3 mm (4.3 +/- 0.7 mm), and the narrow gap group was defined as less than 3 mm (1.3 +/- 1.3 mm). RESULTS: Under non-WB (weight bearing) conditions, the wide flexion gap group (N = 10) showed a significant anterior displacement of the medial femoral condyle as compared with the narrow flexion gap group (N = 20). Despite no significant differences observed under WB conditions, both femoral condyle positions during flexion were significantly more posterior than during extension. WOMAC of the tight gap group showed worse scores for two functional items demanding knee flexion (bending to floor and getting on/off toilet). CONCLUSION: The large flexion gap could influence the late rollback under non-WB conditions and better WOMAC functional scores in the flexion items. Three to four millimetre laxity at 90 degrees -0 degrees component gaps may be adequate and might be necessary to carry out daily life activities. PMID- 26133290 TI - Prevalence of associated injuries after anterior shoulder dislocation: a prospective study. AB - PURPOSE: Anterior shoulder dislocation can be associated with many lesions such as Bankart lesions, rotator cuff tears (RCT), Hill-Sachs lesions or greater tuberosity fractures. It has been documented that early management of the associated injury affords better recovery of shoulder function. The aim of this study was to highlight the incidence of associated injuries after anterior shoulder dislocation. METHODS: A total of 240 patients with traumatic anterior glenohumeral dislocations were subjected to complete history taking, neurovascular assessment and pre-reduction plain X-ray. An X-ray was taken immediately after reduction. Ultrasonography (US) and magnetic resonance imaging (MRI) were done within one week after reduction in all patients. Nerve conduction studies were ordered for any patient with suspected nerve injury. RESULTS: Associated lesions were reported in 144 (60%) patients. RCT was the most common injury (67 cases). It was isolated in 34 patients (14.15%), while it was combined with other lesions in 33 cases (13.75%). Axillary nerve injury was encountered in 38 patients, of them 8 (3.33%) were isolated and 30 (12.5%) were combined. Greater tuberosity fracture was found in 37 patients, of them 15 (6.25%) were combined with axillary nerve injury, and in the other 22 patients (9.17%) the fracture was isolated. All cases with Hill-Sachs and Bankart lesion were combined lesions with no isolated cases. There was a significant relation between the incidence of associated injuries and age, mechanism of injury and the affected side. CONCLUSIONS: Lesions associated with traumatic anterior glenohumeral dislocations are more frequent than expected. Thorough clinical examination and detailed imaging including US and MRI are mandatory to avoid a missed diagnosis. PMID- 26133291 TI - (E)- and (Z)-stereodefined enol phosphonates derived from beta-ketoesters: stereocomplementary synthesis of fully-substituted alpha,beta-unsaturated esters. AB - A versatile, robust, and stereocomplementary synthesis of fully-substituted (E)- and (Z)-stereodefined alpha,beta-unsaturated esters 3 from accessible alpha substituted beta-ketoesters 1via (E)- and (Z)-enol phosphonates was achieved. The present method involves two accessible reaction sequences: (i) (E)- and (Z) stereocomplementary enol phosphorylations of a wide variety of beta-ketoesters 1 (24 examples; 71-99% yield, each >95: 5 ds), and (ii) (E)- and (Z) stereoretentive Suzuki-Miyaura cross-coupling (16 examples; 71-91% yield, >81/19 ds) and Negishi cross-coupling (32 examples; 65-96% yield, >95 : 5 ds) using (E)- and (Z)-enol phosphonates 2. 1H-NMR monitoring for a key reactive N phosphorylammonium (imidazolium) intermediate I and an application in the synthesis of both (E)- and (Z)-tamoxifen precursors 6 are described. PMID- 26133292 TI - Living long and ageing well: is epigenomics the missing link between nature and nurture? AB - Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50% of the variability in human lifespan with another 25% explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages. PMID- 26133293 TI - Is Meta-Analysis for Utility Values Appropriate Given the Potential Impact Different Elicitation Methods Have on Values? AB - A growing number of published articles report estimates from meta-analysis or meta-regression on health state utility values (HSUVs), with a view to providing input into decision-analytic models. Pooling HSUVs is problematic because of the fact that different valuation methods and different preference-based measures (PBMs) can generate different values on exactly the same clinical health state. Existing meta-analyses of HSUVs are characterised by high levels of heterogeneity, and meta-regressions have identified significant (and substantial) impacts arising from the elicitation method used. The use of meta-regression with few utility values and inclusion criteria that extend beyond the required utility value has not helped. There is the potential to explore greater use of mapping between different PBMs and valuation methods prior to data synthesis, which could support greater use of pooling values. Researchers wishing to populate decision analytic models have a responsibility to incorporate all high-quality evidence available. In relation to HSUVs, greater understanding of the differences between different methods and greater consistency of methodology is required before this can be achieved. PMID- 26133294 TI - [In Process Citation]. PMID- 26133295 TI - [Initial treatment of severely injured patients: A challenge for trauma surgery]. PMID- 26133296 TI - Molecular characterization of a novel mycovirus from Rhizoctonia fumigata AG-Ba isolate C-314 Baishi. AB - The complete genome sequence of a novel dsRNA virus isolated from Rhizoctonia fumigata AG-Ba isolate C-314 Baishi (designated as Rhizoctonia fumigata virus 1, RfV1) was determined. The RfV1 genome was 9,907 bp in length and contained two open reading frames (ORFs). ORF1 potentially coded for a 198.10-kDa protein (P1). P1 shared low but significant amino acid sequence similarity to the putative protein encoded by Lentinula edodes mycovirus (LeV) ORF1. P1 contained a NUDIX domain, which was also present in the putative proteins encoded by the ORF1s of LeV and Phlebiopsis gigantea large virus 1 (PgLV-1). ORF2 potentially coded for a 146.72-kDa protein (P2) that contained the conserved motifs of the RNA-dependent RNA polymerase (RdRp). ORF1 and ORF2 were overlapping, and it was predicted that ORF2 could be translated as a fusion with ORF1 via a ribosomal -1 frameshifting mechanism. Phylogenetic analysis indicated that RfV1 clustered with PgLV-1, LeV and Rosellinia necatrix megabirnavirus 1 (RnMBV1) in a separate clade independent of other virus genera. We propose that RfV1, along with PgLV-1 and LeV, should be grouped into a new viral genus related to the family Megabirnaviridae. This is the first report of the full-length genome sequence of a novel mycovirus isolated from R. fumigata. PMID- 26133297 TI - Laparoscopic major hepatectomies: current trends and indications. A comparison with the open technique. AB - Diffusion of laparoscopic major hepatectomies is experiencing a steady increasing trend, although slower compared to minor resections. The aim of this single center study is to discuss current trends and indications in the application of minimally invasive techniques to major hepatic resections. Preoperative patients and disease characteristics of 49 laparoscopic major hepatectomies (LPS group), performed between 2005 and 2015, were compared with 585 open hepatectomies (Open group) to analyze differences in patients recruitment. Factors which were found to be differently distributed between groups were used as covariates in a propensity score-based case-matched analysis with a 1:3 ratio between LPS group and 147 patients from the Open group (constituting Open-mat group). Short-term outcome was analyzed in matched groups. ASA score, previous abdominal surgery, previous interventional procedures, indication, lesion size and associated procedures were significantly different between the LPS and the Open group. Short term outcome analysis revealed that blood loss (200 vs 350 mL, p = 0.044) and time for functional recovery (3 vs 4 days, p = 0.05) were reduced in the LPS compared to the Open-mat group, in spite of longer length of surgery (260 vs 170 min, p = 0.041) and comparable oncological adequacy. Even though data on technical feasibility of laparoscopic major resections and their benefits in terms of blood loss and functional recovery support the diffusion of minimally invasive approach, the limit of the technique is still represented by the reduced pool of suitable candidates. PMID- 26133298 TI - Protein-energy malnutrition at mid-adulthood does not imprint long-term metabolic consequences in male rats. AB - PURPOSE: The long-term effects of the development of chronic metabolic diseases such as type 2 diabetes and obesity have been associated with nutritional insults in critical life stages. In this study, we evaluated the effect of a low-protein diet on metabolism in mid-adulthood male rats. METHODS: At 90 days of age, Wistar male rats were fed a low-protein diet (4.0 %, LP group) for 30 days, whereas control rats were fed a normal-protein diet (20.5 %, NP group) throughout their lifetimes. To allow for dietary rehabilitation, from 120 to 180 days of age, the LP rats were fed a normal-protein diet. Then, we measured body composition, fat stores, glucose-insulin homeostasis and pancreatic islet function. RESULTS: At 120 days of age, just after low-protein diet treatment, the LP rats displayed a strong lean phenotype, hypoinsulinemia, as assessed under fasting and glucose tolerance test conditions, as well as weak pancreatic islet insulinotropic response to glucose and acetylcholine (p < 0.01). At 180 days of age, after poor protein diet rehabilitation, the LP rats displayed a slight lean phenotype (p < 0.05), which was associated with a high body weight gain (p < 0.001). Additionally, fat pad accumulation, glycemia and insulinemia, as well as the pancreatic islet insulinotropic response, were not significantly different between the LP and NP rats (p > 0.05). CONCLUSIONS: Taken together, the present data suggest that the effects of dietary restriction as a stressor in adulthood are reversible with dietary rehabilitation, indicating that adulthood is not a sensitive or critical time window for metabolic programming. PMID- 26133299 TI - Bee's honey attenuates non-alcoholic steatohepatitis-induced hepatic injury through the regulation of thioredoxin-interacting protein-NLRP3 inflammasome pathway. AB - PURPOSE: We aim to examine whether honey ameliorates hepatic injury in non alcoholic steatohepatitis (NASH) animal and cell line steatosis models. METHODS: NASH was induced in female Sprague-Dawley rat by 8-week feeding with a high-fat diet. During the experiment, 5 g/kg honey was intragastrically fed daily. Rat normal hepatocyte BRL-3A cell was treated with sodium palmitate (SP) to induce steatosis in the absence or presence of honey pre-treatment or specific siRNA/overexpress plasmid of thioredoxin-interacting protein (TXNIP) or antagonist/agonist of Nod-like receptor protein 3 (NLRP3). RESULTS: Honey significantly improved the high-fat-diet-induced hepatic injury, steatosis, fibrosis, oxidative stress, and inflammation in rats. Honey also inhibited the overexpression of TXNIP and the activation of NLRP3 inflammasome. These effects were replicated in BRL-3A cell line which showed that the down-regulation of TXNIP or inhibition of NLRP3 contributed to the suppression of NLRP3 inflammasome activation, inflammation, and re-balanced lipid metabolism. In contrast, overexpression of TXNIP or agonism of NLRP3 exacerbated the cellular damage induced by SP. CONCLUSION: Suppression of the TXNIP-NLRP3 inflammasome pathway may partly contribute to the amelioration of hepatic injury during the progression of NASH by honey. Targeting hepatic TXNIP-NLRP3 inflammasome pathway is a potential therapeutic way for the prevention and treatment of NASH. PMID- 26133300 TI - Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron. AB - Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT3 receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB disruption and brain pathology, (ii) nanoparticles exacerbate SD induced brain damage, and (iii) serotonin 5-HT3 receptor antagonist ondansetron is neuroprotective in SD that is further potentiated byTiO2-nanowired delivery, not reported earlier. PMID- 26133301 TI - Thrombomodulin and High-Sensitive C-Reactive Protein Levels in Blood Correlate with the Development of Cerebral Infarction Among Asians. AB - Our meta-analysis was designed to obtain the correlation between thrombomodulin (TM) and high-sensitive C-reactive protein (hs-CRP) levels and the development of cerebral infarction (CI). Case-control studies relevant to the role plasma TM levels and serum hs-CRP levels in the development of CI were retrieved both electronically and manually and further screened according to a predetermined inclusion and exclusion criteria. All enrolled studies were analyzed for meta regression analyses, sensitivity analyses, and assessments of publication bias. Comprehensive Meta-analysis 2.0 software (CMA 2.0) was used for statistical analysis. A total of 359 studies were initially retrieved, and 13 studies were eventually recruited into our meta-analysis with a total of 881 CI patients (plasma TM levels: n = 513; serum hs-CRP levels: n = 368) and 1067 healthy controls. The results of our meta-analysis suggested that plasma TM levels and serum hs-CRP levels in CI patients were significantly higher than those in healthy controls. In conclusion, increased plasma TM levels and serum hs-CRP levels in CI patients were associated with the development of CI in Asians. PMID- 26133303 TI - Dehydration: Isonatremic, Hyponatremic, and Hypernatremic Recognition and Management. PMID- 26133304 TI - Over-the-Counter Medications: Update on Cough and Cold Preparations. PMID- 26133305 TI - Depression and Suicide in Children and Adolescents. PMID- 26133302 TI - Cerebral Oedema, Blood-Brain Barrier Breakdown and the Decrease in Na(+),K(+) ATPase Activity in the Cerebral Cortex and Hippocampus are Prevented by Dexamethasone in an Animal Model of Maple Syrup Urine Disease. AB - Maple syrup urine disease (MSUD) is a rare metabolic disorder associated with acute and chronic brain dysfunction. This condition has been shown to lead to macroscopic cerebral alterations that are visible on imaging studies. Cerebral oedema is widely considered to be detrimental for MSUD patients; however, the mechanisms involved are still poorly understood. Therefore, we investigated whether acute administration of branched-chain amino acids (BCAA) causes cerebral oedema, modifies the Na(+),K(+)-ATPase activity, affects the permeability of the blood-brain barrier (BBB) and alters the levels of cytokines in the hippocampus and cerebral cortex of 10-day-old rats. Additionally, we investigated the influence of concomitant administration of dexamethasone on the alterations caused by BCAA. Our results showed that the animals submitted to the model of MSUD exhibited an increase in the brain water content, both in the cerebral cortex and in the hippocampus. By investigating the mechanism of cerebral oedema, we discovered an association between H-BCAA and the Na(+),K(+)-ATPase activity and the permeability of the BBB to small molecules. Moreover, the H-BCAA administration increases Il-1beta, IL-6 and TNF-alpha levels in the hippocampus and cerebral cortex, whereas IL-10 levels were decreased in the hippocampus. Interestingly, we showed that the administration of dexamethasone successfully reduced cerebral oedema, preventing the inhibition of Na(+),K(+)-ATPase activity, BBB breakdown and the increase in the cytokines levels. In conclusion, these findings suggest that dexamethasone can improve the acute cerebral oedema and brain injury associated with high levels of BCAA, either through a direct effect on brain capillary Na(+),K(+)-ATPase or through a generalized effect on the permeability of the BBB to all compounds. PMID- 26133306 TI - Index of suspicion. Case 1: Listlessness in a 4-month-old Girl. PMID- 26133307 TI - Index of suspicion. Case 2: Fever and Irritability in a 15-year-old Boy With Autism. PMID- 26133308 TI - Index of suspicion. Case 3: Emesis and Unsteady Gait in 35-month-old Boy. PMID- 26133309 TI - Precocious Puberty. PMID- 26133310 TI - Visual Diagnosis: 20-month-old Boy With a One-Day History of Fever and Cough. PMID- 26133311 TI - Preparation and evaluation of nanocellulose-gold nanoparticle nanocomposites for SERS applications. AB - Nanocellulose is of research interest due to its extraordinary optical, thermal, and mechanical properties. The incorporation of guest nanoparticles into nanocellulose substrates enables production of novel nanocomposites with a broad range of applications. In this study, gold nanoparticle/bacterial cellulose (AuNP/BC) nanocomposites were prepared and evaluated for their applicability as surface-enhanced Raman scattering (SERS) substrates. The nanocomposites were prepared by citrate mediated in situ reduction of Au(3+) in the presence of a BC hydrogel at 303 K. Both the size and morphology of the AuNPs were functions of the HAuCl4 and citrate concentrations. At high HAuCl4 concentrations, Au nanoplates form within the nanocomposites and are responsible for high SERS enhancements. At lower HAuCl4 concentrations, uniform nanospheres form and the SERS enhancement is dependent on the nanosphere size. The time-resolved increase in the SERS signal was probed as a function of drying time with SERS 'hot-spots' primarily forming in the final minutes of nanocomposite drying. The application of the AuNP/BC nanocomposites for detection of the SERS active dyes MGITC and R6G as well as the environmental contaminant atrazine is illustrated as is its use under low and high pH conditions. The results indicate the broad applicability of this nanocomposite for analyte detection. PMID- 26133312 TI - Current Status of Fractional Laser Resurfacing. AB - Fractional lasers were first developed based on observations of lasers designed for hair transplantation. In 2007, ablative fractional laser resurfacing was introduced. The fractionation allowed deeper tissue penetration, leading to greater tissue contraction, collagen production and tissue remodeling. Since then, fractional erbium:YAG resurfacing lasers have also been introduced. These lasers have yielded excellent results in treating photoaging, acne scarring, and dyschromia. With the adjustment of microspot density, pulse duration, number of passes, and fluence, the surgeon can adjust the treatment effects. These lasers have allowed surgeons to treat patients with higher Fitzpatrick skin types (types IV to VI) and greater individualize treatments to various facial subunits. Immunohistochemical analysis has demonstrated remodeling effects of the tissues for several months, producing longer lasting results. Adjuvant treatments are also under investigation, including concomitant face-lift, product deposition, and platelet-rich plasma. Finally, there is a short recovery time from treatment with these lasers, allowing patients to resume regular activities more quickly. Although there is a relatively high safety profile for ablative fractionated lasers, surgeons should be aware of the limitations of specific treatments and the associated risks and complications. PMID- 26133313 TI - Interventions for post-stroke fatigue. AB - BACKGROUND: Post-stroke fatigue (PSF) is a common and distressing problem after stroke. The best ways to prevent or treat PSF are uncertain. Several different interventions can be argued to have a rational basis. OBJECTIVES: To determine whether, among people with stroke, any intervention reduces the proportion of people with fatigue, fatigue severity, or both; and to determine the effect of intervention on health-related quality of life, disability, dependency and death, and whether such intervention is cost effective. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched May 2014), Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 4), MEDLINE (1950 to May 2014), EMBASE (1980 to May 2014), CINAHL (1982 to May 2014), AMED (1985 to May 2014), PsycINFO (1967 to May 2014), Digital Dissertations (1861 to May 2014), British Nursing Index (1985 to May 2014), PEDro (searched May 2014) and PsycBITE (searched May 2014). We also searched four ongoing trials registries, scanned reference lists, performed citation tracking of included trials and contacted experts. SELECTION CRITERIA: Two review authors independently scrutinised all titles and abstracts and excluded obviously irrelevant studies. We obtained the full texts for potentially relevant studies and three review authors independently applied the inclusion criteria. We included randomised controlled trials (RCTs) that compared an intervention with a control, or compared different interventions for PSF. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias for each included trial. The primary outcomes were severity of fatigue, or proportion of people with fatigue after treatment. We performed separate analyses for trials investigating efficacy in treating PSF, trials investigating efficacy in preventing PSF and trials not primarily investigating efficacy in PSF but which reported fatigue as an outcome. We pooled results from trials that had a control arm. For trials that compared different potentially active interventions without a control arm, we performed analyses for individual trials without pooling.We calculated standardised mean difference (SMD) as the effect size for continuous outcomes and risk ratio (RR) for dichotomous outcomes. We pooled the results using a random-effects model and assessed heterogeneity using the I(2) statistic. We performed separate subgroup analyses for pharmacological and non pharmacological interventions. We also performed sensitivity analyses to assess the influence of methodological quality. MAIN RESULTS: We retrieved 12,490 citations, obtained full texts for 58 studies and included 12 trials (three from the 2008 search and nine from the 2014 search) with 703 participants. Eight trials primarily investigated the efficacy in treating PSF, of which six trials with seven comparisons provided data suitable for meta-analysis (five pharmacological interventions: fluoxetine, enerion, (-)-OSU6162, citicoline and a combination of Chinese herbs; and two non-pharmacological interventions: a fatigue education programme and a mindfulness-based stress reduction programme). The fatigue severity was lower in the intervention groups than in the control groups (244 participants, pooled SMD -1.07, 95% confidence interval (CI) -1.93 to -0.21), with significant heterogeneity between trials (I(2) = 87%, degrees of freedom (df) = 6, P value < 0.00001). The beneficial effect was not seen in trials that had used adequate allocation concealment (two trials, 89 participants, SMD -0.38, 95% CI -0.80 to 0.04) or trials that had used adequate blinding of outcome assessors (four trials, 198 participants, SMD -1.10, 95% CI 2.31 to 0.11).No trial primarily investigated the efficacy in preventing PSF.Four trials (248 participants) did not primarily investigate the efficacy on fatigue but other symptoms after stroke. None of these interventions showed any benefit on reducing PSF, which included tirilazad mesylate, continuous positive airway pressure for sleep apnoea, antidepressants and a self management programme for recovery from chronic diseases. AUTHORS' CONCLUSIONS: There was insufficient evidence on the efficacy of any intervention to treat or prevent fatigue after stroke. Trials to date have been small and heterogeneous, and some have had a high risk of bias. Some of the interventions described were feasible in people with stroke, but their efficacy should be investigated in RCTs with a more robust study design and adequate sample sizes. PMID- 26133314 TI - Supramolecular Fluorescent Nanoparticles Constructed via Multiple Non-Covalent Interactions for the Detection of Hydrogen Peroxide in Cancer Cells. AB - Overabundance of hydrogen peroxide originating from environmental stress and/or genetic mutation can lead to pathological conditions. Thus, the highly sensitive detection of H2 O2 is important. Herein, supramolecular fluorescent nanoparticles self-assembled from fluorescein isothiocyanate modified beta-cyclodextrin (FITC beta-CD)/rhodamine B modified ferrocene (Fc-RB) amphiphile were prepared through host-guest interaction between FITC-beta-CD host and Fc-RB guest for H2 O2 detection in cancer cells. The self-assembled nanoparticles based on a combination of multiple non-covalent interactions in aqueous medium showed high sensitivity to H2 O2 while maintaining stability under physiological condition. Owing to the fluorescence resonance energy transfer (FRET) effect, addition of H2 O2 led to obvious fluorescence change of nanoparticles from red (RB) to green (FITC) in fluorescent experiments. In vitro study showed the fluorescent nanoparticles could be efficiently internalized by cancer cells and then disrupted by endogenous H2 O2 , accompanying with FRET from "on" to "off". These supramolecular fluorescent nanoparticles constructed via multiple non-covalent interactions are expected to have potential applications in diagnosis and imaging of diseases caused by oxidative stresses. PMID- 26133315 TI - Ceftolozane/Tazobactam: A Novel Cephalosporin/beta-Lactamase Inhibitor Combination. AB - Ceftolozane/tazobactam is a novel antipseudomonal beta-lactam/beta-lactamase inhibitor combination that is currently approved by the United States Food and Drug Administration for the treatment of complicated intraabdominal infections (cIAI) and complicated urinary tract infections (cUTI). It exhibits bactericidal properties through inhibition of bacterial cell wall biosynthesis, which is mediated through penicillin-binding proteins (PBPs). Ceftolozane is a potent PBP3 inhibitor and has a higher affinity for PBP1b compared with other beta-lactam agents. Ceftolozane/tazobactam differs from other cephalosporins due to its increased activity against some AmpC beta-lactamases and Pseudomonas aeruginosa. The addition of tazobactam provides enhanced activity against extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and certain anaerobic organisms. Population pharmacokinetic studies for ceftolozane and ceftolozane/tazobactam are best described by a two-compartment model with zero order input and linear elimination. Similar to other cephalosporins, the best pharmacodynamic property to predict efficacy for ceftolozane/tazobactam is a concentration that remains above the minimum inhibitory concentration (MIC) for 40-50% of the dosing interval. For Enterobacteriaceae and P. aeruginosa strains, the time above the MIC (T > MIC) needed to produce bactericidal activity was much less with ceftolozane than other cephalosporins, with T > MIC requirements of approximately 30%. For currently approved indications, the dose of ceftolozane/tazobactam is 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) intravenously every 8 hours given as a 1-hour infusion. Ceftolozane has low plasma protein binding (20%) and is predominantly excreted unchanged in the urine (>= 92%). Dosage adjustments are required for moderate-to-severe renal impairment and in patients receiving hemodialysis. Based on data from clinical trials, adverse effects due to ceftolozane/tazobactam do not differ considerably from other cephalosporins, with the most common being nausea, diarrhea, headache, and pyrexia. Ceftolozane/tazobactam is a promising new agent for the treatment of cIAI and cUTI, including those caused by multidrug-resistant gram-negative organisms. PMID- 26133316 TI - Subclinical Carotid Atherosclerosis Burden in the Japanese: Comparison between Okinawa and Nagano Residents. AB - AIM: The prevalence of overweight and a change in atherosclerotic lipid profiles may be linked to region-specific differences in atherosclerotic diseases. We evaluated whether the lipid phenotype could be linked to region- and sex-specific differences in the degree of atherosclerosis. METHODS: Non-diabetic subjects included Okinawa (n=1674) and Nagano (n=1392) residents aged 30-75 years who underwent carotid ultrasonography for the measurement of maximum intima-media thickness (max IMT). RESULTS: Average max IMT was higher in Okinawa men and women, and the increase in max IMT with age was enhanced in men. Multiple regression analysis showed that in addition to age and systolic blood pressure, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol were IMT determinants only in men for both Okinawa and Nagano. Meanwhile, HDL cholesterol was a determinant for Okinawa men and women, but not for Nagano men and women. CONCLUSIONS: This is the first report to show region- and sex-specific differences in the determinants for max IMT in a Japanese population. The evaluation of the relationship between lipid profile patterns and region- and sex specific differences in carotid atherosclerosis burden may be required. PMID- 26133317 TI - ATF3 Inhibits Tenascin-C-induced Foam Cell Formation in LPS-Stimulated THP-1 Macrophages by Suppressing TLR-4. AB - AIM: Efficiently inhibiting the formation of macrophage foam cells is indispensable for mitigating and treating atherosclerosis. Tenascin-C (TN-C) plays an important role in promoting atherosclerosis; therefore, it is essential to inhibit foam cell formation associated with TN-C for controlling atherosclerosis. Activating transcription factor 3 (ATF3) is one of the factors involved in regulating the complex process of foam cell formation. This study aimed to explore the role of TN-C and ATF3 in LPS-stimulated THP-1-derived macrophages. METHODS: RT-PCR was used for evaluating the expression of TN-C in LPS-stimulated THP-1 macrophages. Further, exogenous TN-C was introduced and incubated with cultured THP-1 macrophages to confirm the effect of TN-C on LPS stimulated THP-1 macrophages. ATF3-modified THP-1 macrophages were constructed and verified by western blot. High performance liquid chromatography (HPLC) assay and Oil red O staining were applied for detecting cholesteryl ester/total cholesterol (CE/TC) and lipid formation in THP-1 macrophages. RESULTS: The expression of TN-C was determined to be upregulated in LPS-stimulated THP-1 macrophages in a dose- and time-dependent manner. HPLC assay and Oil red O staining confirmed that TN-C can enhance LPS-induced THP-1 macrophage foam cell formation. Moreover, ATF3 can act as a negative regulatory factor for inhibiting TN-C-induced foam cell formation by suppressing TLR-4 in LPS-stimulated THP-1 macrophages. CONCLUSION: ATF3 can inhibit TN-C-induced foam cell formation in LPS stimulated THP-1 macrophages by suppressing TLR-4. It may be a useful molecular target to control TN-C-induced foam cell formation in atherosclerosis. PMID- 26133318 TI - Association between Ophthalmological Changes and Cardiovascular Diseases in Patients with Chronic Kidney Disease Undergoing Hemodialysis. AB - AIMS: Patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) have a high prevalence of cardiovascular diseases (CVD). Arterial sclerosis plays an important role in the pathogenesis of CVD. However, to date, there have been no reports of assessment of the association between retinal arterial sclerosis and CVD in patients with CKD on HD. The aim of this study was to assess retinal arterial sclerosis and to investigate the relationship between retinal arterial changes in patients with CKD on HD and arterial stiffness/past history of CVD. METHODS: We examined the data of 44 patients (21 female, 23 male) with CKD receiving HD treatment at Saiseikai Kurihashi Hospital. The relationship between ophthalmological changes and arterial stiffness [pulse wave velocity (PWV)] or past history of CVD was evaluated. All medications being taken were recorded, and biochemical parameters were analyzed. RESULTS: Significant correlations were found between the presence of arteriosclerotic retinopathy [Scheie classification S grade (grade 0: 7 patients, grade 1: 18 patients, grade 2: 14 patients, grade 3: 4 patients, and grade 4: 1 patient)] and results of the evaluation of arterial stiffness (PWV) and past history of CVD (p=0.001, p=0.045). Other ophthalmological findings were not associated with a history of CVD or arterial stiffness. CONCLUSION: We showed that the classification (Scheie S grade) of retinopathy on ophthalmoscopic examination may be a useful tool for predicting arterial stiffness and its association with CVD. PMID- 26133319 TI - Critically ill Patients and Platelet-Derived Microparticles. PMID- 26133320 TI - Gadolinium deposition in the brain: another concern regarding gadolinium-based contrast agents. PMID- 26133322 TI - The fate of abstracts presented at Turkish national radiology congresses in 2010 2012. AB - PURPOSE: This study aims to evaluate the analysis and publication rates of abstracts presented at the Turkish National Radiology meetings in 2010-2012. METHODS: Abstracts presented in the national radiology meetings of 2010, 2011, and 2012 were included in the study. The presentations were classified according to presentation type (oral or poster presentations), study type, study design, imaged organ or body systems, imaging modalities, time interval between the presentation and the publication date, and the journal in which the article was published. The conversion rate of presentations into full-text articles in peer reviewed journals were surveyed through PubMed. The time from presentation in the meetings to publication was determined. The distribution of journals was also demonstrated. RESULTS: The total number of presentations submitted in three national radiology meetings was 3,192. The publication rate was 11% for the 2010 meeting, 8.2% for the 2011 meeting, and 9.6% for the 2012 meeting. A total of 300 papers were published, with an average of 15 months (range, 0-42 months) between presentation and final publication. The first three refereed international journals with the most number of papers derived from these meetings were Diagnostic and Interventional Radiology, Clinical Imaging, and European Journal of Radiology. CONCLUSION: The overall publication rate of scientific abstracts from Turkey was lower than those from overseas countries. Encouraging the authors to conduct higher-quality research would raise the publication rate as well as improve the quality and success of our scientific meetings. PMID- 26133321 TI - The role of computed tomography in the diagnosis of acute and chronic pulmonary embolism. AB - Pulmonary embolism (PE) is a potentially life threatening condition requiring adequate diagnosis and treatment. Computed tomography pulmonary angiography (CTPA) is excellent for including and excluding PE, therefore CT is the first choice diagnostic imaging technique in patients suspected of having acute PE. Due to its wide availability and low invasiveness, CTPA tends to be overused. Correct implementation of clinical decision rules in diagnostic workup for PE improves adequate use of CT. Also, CT adds prognostic value by evaluating right ventricular (RV) function. CT-assessed RV dysfunction and to lesser extent central emboli location predicts PE-related mortality in normotensive and hypotensive patients, while PE embolic obstruction index has limited prognostic value. Simple RV/left ventricular (LV) diameter ratio measures >1.0 already predict risk for adverse outcome, whereas ratios <1.0 can safely exclude adverse outcome. Consequently, assessing the RV/LV diameter ratio may help identify patients who are potential candidates for treatment at home instead of treatment in the hospital. A minority of patients develop chronic thromboembolic pulmonary hypertension (CTEPH) following acute PE, which is a life-threatening condition that can be diagnosed by CT. In proximal CTEPH, involving the more central pulmonary arteries, thrombectomy usually results in good outcome in terms of both functional status and long-term survival rate. CT is becoming the imaging method of choice for diagnosing CTEPH as it can identify patients who may benefit from thrombectomy. New CT developments such as distensibility measurements and dual energy or subtraction techniques may further refine diagnosis and prognosis for improved patient care. PMID- 26133323 TI - 17beta-Estradiol-Loaded PEGlyated Upconversion Nanoparticles as a Bone-Targeted Drug Nanocarrier. AB - Hormone replacement therapy (HRT) plays an important role in the treatment and prevention of osteoporosis. Here, 17beta-estradiol (E2)-loaded PEGlyated upconversion nanoparticles (E2-UCNP@pPEG) were synthesized that retained E2 bioactivity and improved delivery efficiency over a relatively long time-period. E2-UCNP@pPEG was synthesized and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR), among other methods. The loading efficiency of E2 was determined to be 14.5 wt %, and the nanocarrier effectively facilitated sustained release. Confocal upconversion luminescence (UCL) imaging using the CW 980 nm laser as excitation resource revealed significant interactions of E2-UCNP@pPEG with preosteoblasts. E2-UCNP@pPEG treatment of preosteoblasts induced positive effects on differentiation, matrix maturation, and mineralization. Moreover, in situ and ex vivo UCL imaging studies disclosed that E2 encapsulated in the nanocomposite was passively delivered to bone. Our results collectively suggest that this nanoreservoir provides an effective drug-loading system for hormonelike drug delivery and support its considerable potential as a therapeutic agent for osteoporosis. PMID- 26133324 TI - Publication Bias: A remediable form of bias? PMID- 26133325 TI - Reproductive health status and life skills of adolescent girls dwelling in slums in Chennai, India. AB - BACKGROUND: Adolescent girls dwelling in slums are vulnerable to poor reproductive health due to lack of awareness about reproductive health and low life skills. These girls are in a crucial stage of their life cycle and their health can impact the health of future generations. Despite adolescents comprising almost one-quarter of the Indian population they are ill served in terms of reproductive health. METHODS: This cross-sectional study was done among 130 slum-dwelling adolescent girls, aged 13-19 years, using multistage sampling method from five slums in Chennai, southern India. The reproductive and menstrual morbidity profile, personal and environmental menstrual hygiene was assessed to determine their reproductive health-seeking behaviour and life skills. RESULTS: Ninety-five (73%) girls (95% CI 66.23-81.36) reported menstrual morbidity and 66 (51%; 95% CI 50.74-52.25) had symptoms suggestive of reproductive/urinary tract infection. Of the girls surveyed, 55 (42%) were married. Nearly 25% (95% CI 23.07 26.92) of the married girls had a history of abortion and 18% (95% CI 11.32 25.07) had self-treated with medications for the same. Contraceptive use among ever-married girls was 22.7% (95% CI 20.83-24.56). Even though 75% of respondents knew about HIV/AIDS, their knowledge of modes of transmission and prevention were low (39% and 19%, respectively). Almost 39% of respondents felt shame or insecurity as the key barrier for not seeking reproductive healthcare. About 52% had low life skill levels. On logistic regression, menstrual morbidity was high among those with low life skills, symptoms suggestive of reproductive/urinary tract infection were high among those who were married before 14 years of age and life skills were high among those who belonged to the scheduled caste community. CONCLUSION: There is a high prevalence of menstrual/reproductive morbidity, self treated abortion and low knowledge about modes of HIV transmission/prevention and use of contraceptives among adolescent girls in slums in Chennai. There is a need to initiate community-level life skill education, sex education and behaviour change communication. PMID- 26133326 TI - Experience of non-scalpel vasectomy in a rural area of Tamil Nadu. AB - BACKGROUND: Only 0.7% of men participate in the sterilization programme in Tamil Nadu. Various strategies were adopted to achieve a target of 10%. We aimed to assess the motivational strategies adopted by the health staff of Sathya Vijayanagaram block of Thiruvannamalai district in Tamil Nadu to improve the acceptance of non-scalpel vasectomy among the beneficiaries and to describe the sociodemographic characteristics of the acceptors of the technique. METHODS: This qualitative study, conducted in November-December 2010, involved in-depth interviews of the health staff of Cheyyar Health Unit district. All those who accepted non-scalpel vasectomy between 2007 and 2010 were interviewed. RESULTS: Early identification of targets and sustained motivation through a team approach, supported by administrative arrangements and intense information-education communication activities, resulted in non-scalpel vasectomy contributing to 13% of all sterilizations. Acceptors were men from lower socioeconomic strata. CONCLUSION: The strategies adopted by the health system have contributed to the acceptance of non-scalpel vasectomy in the remote villages of a block in Tamil Nadu. This endeavour may be replicated in other districts of Tamil Nadu and others states of India to achieve the goals set for population control. PMID- 26133327 TI - Three siblings with multiform seizures: An unusual presentation of Doose syndrome. AB - Doose syndrome, or epilepsy with myoclonic-atonic seizures, is a rare electroclinical syndrome. It is important to distinguish it from related epilepsy syndromes such as Lennox Gestaut syndrome and Dravet syndrome. We report the occurrence of this disorder in three siblings born of a non-consanguineous marriage. PMID- 26133328 TI - Chronic myeloid leukaemia: A paradigm shift in management. AB - In early 2000, a better understanding of the molecular biology of chronic myeloid leukaemia established a central role for enhanced tyrosine kinase activity leading to targeted therapy with imatinib mesylate. This paradigm shift in the management of this disease has improved the median survival from 8-9 years before 2000 to an estimated 25 years. Rapid research in this area along with well designed multicentric clinical trials have resulted in the development of second- and third-generation tyrosine kinase inhibitors, which are more effective for patients who develop resistance to imatinib. The synergy of haematological, cytogenetic and molecular parameters is the mainstay of monitoring patients with chronic myelod leukaemia. Early identification of patients likely to have suboptimal response to initial tyrosine kinase inhibitors and when to discontinue therapy in those with an optimal response are areas of active research. PMID- 26133329 TI - Risk of pre-eclampsia after kidney donation: Primum non nocere. PMID- 26133330 TI - Community health worker-based intervention for diabetes care: Feasibility and cultural acceptability in India. PMID- 26133331 TI - Should birth preparedness and complication readiness (BPCR) interventions be scaled up in developing countries? PMID- 26133332 TI - Making a postgraduate journal club an effective learning opportunity: Experience from the Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi. PMID- 26133333 TI - Recent trends in the commercialization of medical care in China. PMID- 26133334 TI - The topsy turvy world of drug brand names. PMID- 26133335 TI - The 'middle path' and the perils of moderation in medicine. PMID- 26133336 TI - Manu Liladhar Kothari. PMID- 26133337 TI - Remembering Manubhai Kothari. PMID- 26133338 TI - Adult health and social care integration. PMID- 26133345 TI - An unusual cause of hip pain. PMID- 26133346 TI - Team-based learning in a medical centre in Malaysia: Perspectives of the faculty. PMID- 26133347 TI - Non-aqueous, non-vitreous humour in medical journals. PMID- 26133348 TI - Effect of music on stress and academic performance of undergraduate medical students. PMID- 26133349 TI - Does the present undergraduate curriculum emphasize the principles of enhanced recovery after surgery (ERAS)? PMID- 26133350 TI - Nobel prize in physiology or medicine awarded for discovery of human brain's internal GPS system. PMID- 26133351 TI - Pork nasal packing research paper wins 2014 Ig Nobel prize in medicine. PMID- 26133352 TI - Study published in the NMJI wins Research Paper of the Year award at the BMJ Awards India 2014. PMID- 26133354 TI - Polymer-Doxorubicin Conjugate Micelles Based on Poly(ethylene glycol) and Poly(N (2-hydroxypropyl) methacrylamide): Effect of Negative Charge and Molecular Weight on Biodistribution and Blood Clearance. AB - Well-defined water-soluble block copolymers poly(ethylene glycol)-b-poly(N-(2 hydroxypropyl) methacrylamide-co-N-methacryloylglycylglycine) (PEG-b-P(HPMA-co MAGG)) and their doxorubicin (Dox) conjugates with different composition and molecular weight were synthesized. These Dox conjugates can form micelles in buffer solution. The physicochemical properties, in vivo biodistribution, blood clearance, and especially the tumor accumulation of copolymers and micelles were studied. Severe liver accumulation can be observed for PEG-b-PMAGG copolymers. This was quite different from their Dox conjugate for which decreased RES uptake and elevated kidney accumulation could be observed. When decrease the negative charge to an appropriate amount such as 8-10 mol %, both RES uptake and kidney accumulation could be suppressed. Obvious tumor accumulation could be achieved especially when the molecular weight were increased from ~40 to ~80 KDa. These results provided us with a guideline for the design of nanoscaled drug delivery system as well as a potential option for treating kidney-related cancers. PMID- 26133355 TI - Novel 3-substituted-2-oxoindoline-based N-hydroxypropenamides as histone deacetylase inhibitors and antitumor agents. AB - Histone deacetylases (HDAC) are currently a group of validated targets for anticancer drug discovery and development. In our research program to find novel small molecules targeting these enzymes, we designed and synthesized two series of 3-hydroxyimino-2-oxoindoline- and 3- methoxyimino-2-oxoindoline-based N hydroxypropenamides (3a-g, 6a-g). The results show that these propenamides potently inhibited HDAC2 with IC50 values in sub-micromolar range, approximately 10-fold lower than that of SAHA (also known as suberoylanilohydroxamic acid). Evaluation of cytotoxicity of these compounds in three human cancer cell lines revealed that most of the synthesized compounds were up to 5-fold more cytotoxic than SAHA. Docking studies showed that the compounds bound to HDAC2 at the binding site with higher binding affinities compared to SAHA. Our present results demonstrate that these novel 3-substituted-2-oxoindoline-based N hydroxypropenamides are potential for further development as anticancer agents. PMID- 26133356 TI - Design, green synthesis and pharmacological evaluation of novel 5,6-diaryl-1,2,4 triazines bearing 3-morpholinoethylamine moiety as potential antithrombotic agents (.). AB - The aim of this research work was to investigate a series of novel 5,6-diaryl 1,2,4-triazines (3a-3q) containing 3-morpholinoethylamine side chain, and to address their antiplatelet activity by in vitro, ex vivo and in vivo methods. All compounds were synthesized by environment benign route and their structures were unambiguously confirmed by spectral data. Compounds (3l) and (3m) were confirmed by their single crystal X-ray structures. Out of all the synthesized compounds, 10 were found to be more potent in vitro than aspirin; six of them were found to be prominent in ex vivo assays and one compound (3d) was found to have the most promising antithrombotic profile in vivo. Moreover, compound (3d) demonstrated less ulcerogenicity in rats as compared to aspirin. The selectivity of the most promising compound (3d) for COX-1 and COX-2 enzymes was determined with the help of molecular docking studies and the results were correlated with the biological activity. PMID- 26133357 TI - Monocyclic beta-lactam and unexpected oxazinone formation: synthesis, crystal structure, docking studies and antibacterial evaluation. AB - Novel monocyclic beta-lactam derivatives bearing aryl, phenyl and heterocyclic rings were synthesized as possible antibacterial agents. Cyclization of imines (3h, 3t) with phenylacetic acid in the presence of phosphoryl chloride and triethyl amine did not afford the expected beta-lactams. Instead, highly substituted 1,3-oxazin-4-ones (4h, 4t) were isolated as the only product and confirmed by single crystal X-ray analysis of 4t. The results of antibacterial activity showed that compound 4l exhibited considerable antibacterial activity with MIC and MBC values of 62.5 ug/mL against Klebsiella pneumoniae. Cytotoxicity assay on Chinese Hamster Ovary (CHO) cell line revealed non-cytotoxic behavior of compounds 4d, 4h, 4k and 4l up to 200 MUg/mL conc. Molecular docking was performed for compound 4l with penicillin binding protein-5 to identify the nature of interactions. The results of both in silico and in vitro evaluation provide the basis for compound 4l to be carried as a potential lead molecule in the drug discovery pipeline against bacterial infections. PMID- 26133358 TI - The Prototype of Indicators of a Responsive Partner Shapes Information Processing: A False Recognition Study. AB - When judging whether a relationship partner can be counted on to "be there" when needed, people may draw upon knowledge structures to process relevant information. We examined one such knowledge structure using the prototype methodology: indicators of a partner who is likely to be there when needed. In the first study (N = 91), the structure, content, and reliability of the prototype of indicators were examined. Then, using a false recognition study (N = 77), we demonstrated that once activated, the prototype of indicators of a partner who is likely to be there when needed affects information processing. Thus, the prototype of indicators may shape how people process support-relevant information in everyday life, affecting relationship outcomes. Using this knowledge structure may help a person process relevant information quickly and with cognitive economy. However, it may also lead to biases in judgments in certain situations. PMID- 26133359 TI - Tn7-Based Device for Calibrated Heterologous Gene Expression in Pseudomonas putida. AB - The soil bacterium Pseudomonas putida is increasingly attracting considerable interest as a platform for advanced metabolic engineering through synthetic biology approaches. However, genomic context, gene copy number, and transcription/translation interplay often introduce considerable uncertainty to the design of reliable genetic constructs. In this work, we have established a standardized heterologous expression device in which the promoter strength is the only variable; the remaining parameters of the flow have stable default values. To this end, we tailored a mini-Tn7 delivery transposon vector that inserts the constructs in a single genomic locus of P. putida's chromosome. This was then merged with a promoter insertion site, an unvarying translational coupler, and a downstream location for placing the gene(s) of interest under fixed assembly rules. This arrangement was exploited to benchmark a collection of synthetic promoters with low transcriptional noise in this bacterial host. Growth experiments and flow cytometry with single-copy promoter-GFP constructs revealed a robust, constitutive behavior of these promoters, whose strengths and properties could be faithfully compared. This standardized expression device significantly extends the repertoire of tools available for reliable metabolic engineering and other genetic enhancements of P. putida. PMID- 26133360 TI - Sexual Dysfunction in Cancer Patients and Survivors #293. PMID- 26133361 TI - Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems. AB - PURPOSE: To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. MATERIALS AND METHODS: All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. RESULTS: On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. CONCLUSION: The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. PMID- 26133362 TI - Irreversible optic neuritis after infliximab treatment in a patient with ulcerative colitis. AB - This article reports the first known case of permanent blindness due to irreversible unilateral optic neuritis (ON) related to infliximab (Remicade) treatment of a patient with ulcerative colitis. A young male, with a family history of inflammatory bowel disease, was diagnosed with ulcerative colitis at the age of 20. He was treated with steroids and a 5-aminosalicylic acid drug without considerable effect, and later admitted to our hospital due to a relapse during reduction of the prednisolone dosage. A new colonoscopy showed moderate ulcerative colitis activity and the patient was declared as a steroid nonresponder. A treatment of 400 mg intravenous infliximab was initiated along with 150 mg/day of azathioprine (Imurel). Three days after the second infliximab treatment the patient woke up with no vision on the left eye and with pain during ocular movement. Brain and orbitae magnetic resonance imaging showed ON on the left optical nerve without any abscess or thrombosis. The patient was treated with 1000 mg methylprednisolone (Solu-Medrol) intravenous for 3 days and afterward with 75 mg prednisolone orally without any effect. At the 3-month follow up, the patient's vision had not improved, and he was declared permanently blind on the left eye. A neurologist also examined the patient, but no abnormality or cause of the ON was found. PMID- 26133364 TI - The evidential value of developmental age imaging for assessing age of majority. AB - AIM: To consider the evidential value of developmental age images for identifying age of majority. METHODS: The published literature on hand-wrist X-rays, MRI scans of the distal radius and orthopantomograms of the lower left third molar is considered in terms of the mean age of attainment of the adult appearance and the diagnostic test performance of the adult appearance to predict adult status, either administratively (under-17 football) or forensically. RESULTS: The mean age of attainment of a mature hand-wrist X-ray is under 18 years and most individuals are mature before age 18. For the MRI wrist scan and the third molar the age of attainment is over 19 years and the adult appearance is an indicator of adulthood, while the immature appearance is uninformative about likely age. So MRI and third molars have high specificity, but low sensitivity. CONCLUSIONS: Bone age assessed by hand-wrist X-ray is uninformative and should not be used. The adult appearance of MRI wrist scans and third molars provide evidence of being over-age, although there remains a small risk of minors being misclassified as adult. The immature appearance is uninformative about likely age and, overall, more than one third of assessments are wrong. PMID- 26133363 TI - Lower Preprandial Insulin and Altered Fuel Use in HIV/Antiretroviral-Exposed Infants in Cameroon. AB - CONTEXT: Intrauterine HIV/antiretroviral (ARV) and postnatal ARVs are known to perturb energy metabolism and could have permanent effects on future metabolic health. Such maladaptive effects could be mediated by changes in mitochondrial function and intermediary metabolism due to fetal and early-life ARV exposure in HIV/ARV-exposed uninfected (HEU) infants. OBJECTIVE: The objective of the study was to understand the relationship(s) between mitochondrial fuel use (assessed via acylcarnitines and branched chain amino acids) and preprandial insulin in infants exposed to in utero HIV/ARV plus postnatal zidovudine or nevirapine compared with HIV/ARV-unexposed uninfected (HUU) infants. DESIGN: This was a prospective cohort study with the following three groups: 1) intrauterine HIV/ARV/postnatal zidovudine-exposed (HEU-A), 2) intrauterine HIV/ARV/postnatal nevirapine-exposed (HEU-N), and 3) HUU infants. Principal component analysis and linear regression modeling were performed to assess the association between in utero HIV/ARV exposure and infant insulin. SETTING: The study was conducted at Cameroonian urban antenatal centers. PARTICIPANTS: HIV-infected and -uninfected pregnant woman/infant dyads participated in the study. MAIN OUTCOME: Preprandial insulin was the main outcome measured. RESULTS: Of 366 infants, 38 were HEU-A, 118 HEU-N. Forty intermediary metabolites were consolidated into seven principal components. In a multivariate analysis, both HEU-A (beta = -.116, P= .012) and HEU-N (beta = -.070, P= .022) demonstrated lower insulin compared with HUU infants. However, at high levels of plasma metabolites, HEU-A (beta = .027, P= .050) exhibited higher insulin levels than HEU-N or HUU infants. A unique array of short-chain acylcarnitines (beta = .044, P= .001) and branched-chain amino acids (beta = .033, P= .012) was associated with insulin. CONCLUSION: HEU-A and HEU-N infants have lower preprandial insulin levels at 6 weeks of age and appear to use metabolic fuel substrates differently than HUU infants. Future studies are warranted to determine whether observed differences have lasting metabolic implications, such as later insulin resistance. PMID- 26133365 TI - Challenges facing European agriculture and possible biotechnological solutions. AB - Agriculture faces many challenges to maximize yields while it is required to operate in an environmentally sustainable manner. In the present study, we analyze the major agricultural challenges identified by European farmers (primarily related to biotic stresses) in 13 countries, namely Belgium, Bulgaria, the Czech Republic, France, Germany, Hungary, Italy, Portugal, Romania, Spain, Sweden, UK and Turkey, for nine major crops (barley, beet, grapevine, maize, oilseed rape, olive, potato, sunflower and wheat). Most biotic stresses (BSs) are related to fungi or insects, but viral diseases, bacterial diseases and even parasitic plants have an important impact on yield and harvest quality. We examine how these challenges have been addressed by public and private research sectors, using either conventional breeding, marker-assisted selection, transgenesis, cisgenesis, RNAi technology or mutagenesis. Both national surveys and scientific literature analysis followed by text mining were employed to evaluate genetic engineering (GE) and non-GE approaches. This is the first report of text mining of the scientific literature on plant breeding and agricultural biotechnology research. For the nine major crops in Europe, 128 BS challenges were identified with 40% of these addressed neither in the scientific literature nor in recent European public research programs. We found evidence that the private sector was addressing only a few of these "neglected" challenges. Consequently, there are considerable gaps between farmer's needs and current breeding and biotechnology research. We also provide evidence that the current political situation in certain European countries is an impediment to GE research in order to address these agricultural challenges in the future. This study should also contribute to the decision-making process on future pertinent international consortia to fill the identified research gaps. PMID- 26133366 TI - The evaluation of MCI, MI, PMI and GT on both genders with different age and dental status. AB - OBJECTIVES: The aim of this study was to measure the mandibular cortical index (MCI), mental index (MI), panoramic mandibular index (PMI) and cortical bone thickness in the zone of the gonial angle (GT) in panoramic radiographies from a large sample of males and females and to determine how they relate to patients' age, gender and dental status. METHODS: 910 panoramic radiographs were obtained and grouped into age, dental status and gender. The MCI, MI, PMI and GT were analysed. RESULTS: Remarkable differences were observed for MCI and GT regarding gender, age groups and dental status on both sides (p < 0.05). While age and dental status had an effect on the MI and PMI in females, dental status had an effect on the MI and PMI in males (p < 0.05). Also, gender had an effect on the MI and PMI (p < 0.05). CONCLUSIONS: The effects of age and tooth loss are different in females and males. In females, the harmful effects of tooth loss and age are more prominent according to the PMI and MI measurements. The effects of age and tooth loss in the GT and MCI measurements are similar, and these indices can be accepted as more reliable in studies including both genders. PMID- 26133367 TI - Proposal of a hybrid approach for tumor progression and tumor-induced angiogenesis. AB - One of the main challenges in cancer modelling is to improve the knowledge of tumor progression in areas related to tumor growth, tumor-induced angiogenesis and targeted therapies efficacy. For this purpose, incorporate the expertise from applied mathematicians, biologists and physicians is highly desirable. Despite the existence of a very wide range of models, involving many stages in cancer progression, few models have been proposed to take into account all relevant processes in tumor progression, in particular the effect of systemic treatments and angiogenesis. Composite biological experiments, both in vitro and in vivo, in addition with mathematical modelling can provide a better understanding of theses aspects. In this work we proposed that a rational experimental design associated with mathematical modelling could provide new insights into cancer progression. To accomplish this task, we reviewed mathematical models and cancer biology literature, describing in detail the basic principles of mathematical modelling. We also analyze how experimental data regarding tumor cells proliferation and angiogenesis in vitro may fit with mathematical modelling in order to reconstruct in vivo tumor evolution. Additionally, we explained the mathematical methodology in a comprehensible way in order to facilitate its future use by the scientific community. PMID- 26133368 TI - Social representations of male circumcision as prophylaxis against HIV/AIDS in Zimbabwe. AB - BACKGROUND: The World Health Organisation recommended the scale-up of voluntary medical male circumcision (VMMC) as an additional HIV prevention method in 2007 and several countries with high HIV prevalence rates including Zimbabwe have since adopted the procedure. Since then researchers have been preoccupied with establishing the level of knowledge and acceptability of circumcision in communities that did not traditionally circumcise. Despite evidence to suggest that knowledge and acceptability of voluntary medical male circumcision is high, there is also emerging evidence that suggest that uptake of circumcision among men has been below expectations. The purpose of this study was thus to investigate people's representations of male circumcision that may influence its uptake. METHODS: Data for this study was collected through focus group discussions with men and women aged between 18 and 49 years. This age group was selected because they are still very sexually active and are within the target population of the upscale of voluntary medical male circumcision programme. Women were included in the study because they would be directly involved in a decision to have their son(s) get circumcised for HIV prevention. The study was carried out in Harare, Zimbabwe. Obtained qualitative data was analysed using thematic content analysis. RESULTS: Results suggest that circumcision is perceived as an alien culture or something for "younger" men or "boys" who are not yet married. The findings also suggest that there are beliefs that circumcision maybe associated with satanic rituals. The issue of condom use after circumcision was also discussed and it was found that some men do not see the need for using condoms after getting circumcised. CONCLUSIONS: There is an urgent need for the development of communications that directly address the misconceptions about voluntary medical male circumcision. There is need for communication that encourages circumcised men to continue using condoms. PMID- 26133369 TI - The Assessment of Motor and Process Skills as a measure of ADL ability in schizophrenia. AB - BACKGROUND: Functional impairments in schizophrenia are substantial, complex, and persistent. Objective measurement of ADL ability, functional capacity and performance is needed for effective intervention planning and outcome evaluation. OBJECTIVE: To evaluate ADL ability in people with schizophrenia using the Assessment of Motor and Process Skills (AMPS) and to determine the utility of using the AMPS to predict levels of assistance required for successful community living. METHOD: In a retrospective audit, AMPS ADL measures of a consecutive sample of 64 people with schizophrenia admitted to a mental health facility were compared with normative data and with recommended "cut-off" measures for competency to live independently in the community. RESULTS: Substantial difficulties were measured in both ADL motor (mean z = -1.5) and ADL process ability (mean z = -2.1). AMPS ability measures did not predict problems with independent living for 62.5% of the patients. CONCLUSION: People with schizophrenia admitted to an inpatient rehabilitation facility experienced significant difficulty performing ADL tasks. AMPS is a useful measure of ADL ability but should be used in conjunction with measures of functional performance in order to plan interventions and supports for people with schizophrenia that reflect the complexity of factors affecting community functioning. PMID- 26133370 TI - Reversibility of Defective Hematopoiesis Caused by Telomere Shortening in Telomerase Knockout Mice. AB - Telomere shortening is common in bone marrow failure syndromes such as dyskeratosis congenita (DC), aplastic anemia (AA) and myelodysplastic syndromes (MDS). However, improved knowledge of the lineage-specific consequences of telomere erosion and restoration of telomere length in hematopoietic progenitors is required to advance therapeutic approaches. We have employed a reversible murine model of telomerase deficiency to compare the dependence of erythroid and myeloid lineage differentiation on telomerase activity. Fifth generation Tert-/- (G5 Tert-/-) mice with shortened telomeres have significant anemia, decreased erythroblasts and reduced hematopoietic stem cell (HSC) populations associated with neutrophilia and increased myelopoiesis. Intracellular multiparameter analysis by mass cytometry showed significantly reduced cell proliferation and increased sensitivity to activation of DNA damage checkpoints in erythroid progenitors and in erythroid-biased CD150hi HSC, but not in myeloid progenitors. Strikingly, Cre-inducible reactivation of telomerase activity restored hematopoietic stem and progenitor cell (HSPC) proliferation, normalized the DNA damage response, and improved red cell production and hemoglobin levels. These data establish a direct link between the loss of TERT activity, telomere shortening and defective erythropoiesis and suggest that novel strategies to restore telomerase function may have an important role in the treatment of the resulting anemia. PMID- 26133371 TI - Blueberry Anthocyanins-Enriched Extracts Attenuate Cyclophosphamide-Induced Cardiac Injury. AB - We sought to explore the effect of blueberry anthocyanins-enriched extracts (BAE) on cyclophosphamide (CTX)-induced cardiac injury. The rats were divided randomly into five groups including normal control, CTX 100 mg/kg, BAE 80mg/kg, CTX+BAE 20mg/kg and CTX+BAE 80mg/kg groups. The rats in the three BAE-treated groups were administered BAE for four weeks. Seven days after BAE administration, rats in CTX group and two BAE-treated groups were intraperitoneally injected with a single dose of 100 mg/kg CTX. Cardiac injury was assessed using physiological parameters, Echo, morphological staining, real-time PCR and western blot. In addition, cardiotoxicity indices, inflammatory cytokines expression and oxidative stress markers were also detected. Four weeks 20mg/kg and 80mg/kg dose of BAE treatment following CTX exposure attenuated mean arterial blood pressure, heart rate and activities of heart enzymes, improved cardiac dysfunction, left ventricular hypertrophy and fibrosis. Importantly, BAE also attenuated CTX induced LV leukocyte infiltration and inflammatory cytokines expression, ameliorated oxidative stress as well as cardiomyocyte apoptosis. In conclusion, BAE attenuated the CTX-induced cardiac injury and the protective mechanisms were related closely to the anti-inflammatory, antioxidant and anti-inflammatory characteristics of BAE. PMID- 26133372 TI - Blockade of the N-Methyl-D-Aspartate Glutamate Receptor Ameliorates Lipopolysaccharide-Induced Renal Insufficiency. AB - N-methyl-D-aspartate (NMDA) receptor activation in rat kidney reduces renal perfusion and ultrafiltration. Hypoperfusion-induced ischemia is the most frequent cause of functional insufficiency in the endotoxemic kidney. Here, we used non-hypotensive rat model of lipopolysaccharide-induced endotoxemia to examine whether NMDA receptor hyperfunction contributes to acute kidney injury. Lipopolysaccharide-induced renal damage via increased enzymuria and hemodynamic impairments were ameliorated by co-treatment with the NMDA receptor blocker, MK 801. The NMDA receptor NR1 subunit in the rat kidney mainly co-localized with serine racemase, an enzyme responsible for synthesizing the NMDA receptor co agonist, D-serine. The NMDA receptor hyperfunction in lipopolysaccharide-treated kidneys was demonstrated by NR1 and serine racemase upregulation, particularly in renal tubules, and by increased D-serine levels. Lipopolysaccharide also induced cell damage in cultured tubular cell lines and primary rat proximal tubular cells. This damage was mitigated by MK-801 and by small interfering RNA targeting NR1. Lipopolysaccharide increased cytokine release in tubular cell lines via toll like receptor 4. The release of interleukin-1beta from these cells are the most abundant. An interleukin-1 receptor antagonist not only attenuated cell death but also abolished lipopolysaccharide-induced NR1 and serine racemase upregulation and increases in D-serine secretion, suggesting that interleukin-1beta-mediated NMDA receptor hyperfunction participates in lipopolysaccharide-induced tubular damage. The results of this study indicate NMDA receptor hyperfunction via cytokine effect participates in lipopolysaccharide-induced renal insufficiency. Blockade of NMDA receptors may represent a promising therapeutic strategy for the treatment of sepsis-associated renal failure. PMID- 26133374 TI - Anthropometric Risk Factors for Differentiated Thyroid Cancer in Young Men and Women From Eastern France: A Case-Control Study. AB - The incidence of thyroid cancer has risen over the past decade, along with a rise in obesity. We studied the role of anthropometric risk factors for differentiated thyroid cancer at the time of diagnosis and at age 20 years in a case-control study conducted in eastern France between 2005 and 2010. The study included 761 adults diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006. They were matched with 825 controls from the general population. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, those with papillary cancer only, and women only. The risk of thyroid cancer was higher for participants with a high body surface area (BSA), great height, or excess weight and for women with a high body fat percentage. Conversely, no significant association was found between body mass index and the risk of thyroid cancer. In the present study, we provide further evidence of the role of BSA and excess weight in the risk of thyroid cancer. These epidemiologic observations should be confirmed by further exploration of the biological mechanisms responsible for the associations of obesity and BSA with thyroid cancer. PMID- 26133375 TI - Hierarchy, Dominance, and Deliberation: Egalitarian Values Require Mental Effort. AB - Hierarchy and dominance are ubiquitous. Because social hierarchy is early learned and highly rehearsed, the value of hierarchy enjoys relative ease over competing egalitarian values. In six studies, we interfere with deliberate thinking and measure endorsement of hierarchy and egalitarianism. In Study 1, bar patrons' blood alcohol content was correlated with hierarchy preference. In Study 2, cognitive load increased the authority/hierarchy moral foundation. In Study 3, low-effort thought instructions increased hierarchy endorsement and reduced equality endorsement. In Study 4, ego depletion increased hierarchy endorsement and caused a trend toward reduced equality endorsement. In Study 5, low-effort thought instructions increased endorsement of hierarchical attitudes among those with a sense of low personal power. In Study 6, participants' thinking quickly allocated more resources to high-status groups. Across five operationalizations of impaired deliberative thought, hierarchy endorsement increased and egalitarianism receded. These data suggest hierarchy may persist in part because it has a psychological advantage. PMID- 26133373 TI - Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication. AB - Kaposi's Sarcoma-Associated Herpesvirus (KSHV) is an oncogenic virus which has adapted unique mechanisms to modulate the cellular microenvironment of its human host. The pathogenesis of KSHV is intimately linked to its manipulation of cellular signaling pathways, including the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. We have previously shown that KSHV ORF45 contributes to the sustained activation of both ERK and p90 ribosomal S6 kinase (RSK, a major functional mediator of ERK/MAPK signaling) during KSHV lytic replication. ORF45-activated RSK is required for optimal KSHV lytic gene expression and progeny virion production, though the underlying mechanisms downstream of this activation are still unclear. We hypothesized that the activation of RSK by ORF45 causes differential phosphorylation of cellular and viral substrates, affecting biological processes essential for efficient KSHV lytic replication. Accordingly, we observed widespread and significant differences in protein phosphorylation upon induction of lytic replication. Mass spectrometry-based phosphoproteomic screening identified putative substrates of ORF45-activated RSK in KSHV-infected cells. Bioinformatic analyses revealed that nuclear proteins, including several transcriptional regulators, were overrepresented among these candidates. We validated the ORF45/RSK-dependent phosphorylation of several putative substrates by employing KSHV BAC mutagenesis, kinase inhibitor treatments, and/or CRISPR-mediated knockout of RSK in KSHV infected cells. Furthermore, we assessed the consequences of knocking out these substrates on ORF45/RSK-dependent regulation of gene expression and KSHV progeny virion production. Finally, we show data to support that ORF45 regulates the translational efficiency of a subset of viral/cellular genes with complex secondary structure in their 5' UTR. Altogether, these data shed light on the mechanisms by which KSHV ORF45 manipulates components of the host cell machinery via modulation of RSK activity. Thus, this study has important implications for the pathobiology of KSHV and other diseases in which RSK activity is dysregulated. PMID- 26133376 TI - Quality Improvement Process in a Large Intensive Care Unit: Structure and Outcomes. AB - Quality improvement in the health care setting is a complex process, and even more so in the critical care environment. The development of intensive care unit process measures and quality improvement strategies are associated with improved outcomes, but should be individualized to each medical center as structure and culture can differ from institution to institution. The purpose of this report is to describe the structure of quality improvement processes within a large medical intensive care unit while using examples of the study institution's successes and challenges in the areas of stat antibiotic administration, reduction in blood product waste, central line-associated bloodstream infections, and medication errors. PMID- 26133377 TI - Antioxidant Properties of Whole Body Periodic Acceleration (pGz). AB - The recognition that oxidative stress is a major component of several chronic diseases has engendered numerous trials of antioxidant therapies with minimal or no direct benefits. Nanomolar quantities of nitric oxide released into the circulation by pharmacologic stimulation of eNOS have antioxidant properties but physiologic stimulation as through increased pulsatile shear stress of the endothelium has not been assessed. The present study utilized a non-invasive technology, periodic acceleration (pGz) that increases pulsatile shear stress such that upregulation of cardiac eNOS occurs, We assessed its efficacy in normal mice and mouse models with high levels of oxidative stress, e.g. Diabetes type 1 and mdx (Duchene Muscular Dystrophy). pGz increased protein expression and upregulated eNOS in hearts. Application of pGz was associated with significantly increased expression of endogenous antioxidants (Glutathioneperoxidase-1(GPX-1), Catalase (CAT), Superoxide, Superoxide Dismutase 1(SOD1). This led to an increase of total cardiac antioxidant capacity along with an increase in the antioxidant response element transcription factor Nrf2 translocation to the nucleus. pGz decreased reactive oxygen species in both mice models of oxidative stress. Thus, pGz is a novel non-pharmacologic method to harness endogenous antioxidant capacity. PMID- 26133378 TI - Hepatitis C Virus Nonstructural Protein 5A Inhibits MG132-Induced Apoptosis of Hepatocytes in Line with NF-kappaB-Nuclear Translocation. AB - BACKGROUND: Hepatitis C virus (HCV) infection is one of the major causes of cirrhosis and hepatocellular carcinoma. HCV nonstructural protein 5A (NS5A) is an attractive antiviral target and plays an important role in HCV replication as well as hepatocarcinogenesis. The aim of this study was to assess the effect of HCV NS5A protein in the abrogation of apoptotic cell death induced by the proteasome inhibitor MG132. METHODS: Apoptotic responses to MG132 and the expression of molecules involved in NF-kappaB signaling pathways in human hepatocytes were investigated with or without the expression of HCV NS5A. RESULTS: HCV NS5A protected HepG2 cells against MG132-induced apoptosis, in line with NF-kappaB-nuclear translocation. A similar NF-kappaB-nuclear translocation was observed in Huh7 cells infected with HCV JFH1. In agreement with this, after treatment with MG132, HCV NS5A could elevate the transcription of several NF kappaB target genes such as BCL2 and BCLXL to inhibit MG132-induced apoptosis in hepatocytes. HCV HCV NS5A also enhanced phosphorylation of IkappaBalpha. Consistent with a conferred prosurvival advantage, HCV NS5A reduced MG132-induced poly(adenosine diphosphate-ribose) polymerase cleavage. CONCLUSIONS: HCV NS5A expression enhances phosphorylation of IkappaBalpha, liberates NF-kappaB for nuclear translocation and downregulates MG132-induced apoptotic pathways in human hepatocytes. It is possible that the disruption of proteasome-associated apoptosis plays a role in the pathogenesis of HCV infection. PMID- 26133381 TI - Healthcare quality and safety in developing countries. PMID- 26133380 TI - Associations of Independent IL2RA Gene Variants with Intermediate Uveitis. AB - PURPOSE: The genetic background for the concomitance of uveitis and other autoimmune diseases remains elusive. Here the role of two IL2RA gene variants (rs11594656 and rs12722495) was investigated in intermediate uveitis and HLAB27 acute anterior uveitis. MATERIALS AND METHODS: One hundred fifty-nine patients with HLAB27 acute anterior uveitis, 85 patients with intermediate uveitis, 138 HLAB27 negative controls and 100 HLAB27 positive controls were recruited for this case-control study. Main outcome measures were genotype distribution and allelic frequencies determined by polymerase chain reaction. RESULTS: The frequencies of carriers of the minor allele at rs11594656 and rs12722495 were significantly different in patients with intermediate uveitis compared to HLAB27 positive and negative controls combined (p<0.05). For rs12722495 the minor G allele was protective (genotypic OR: 0.29 [0.12-0.69]), and for rs11594656 the minor A allele conferred risk (genotypic OR: 1.59 [1.09-2.32]). No significant differences in genotype distribution were found between patients with HLAB27 acute anterior uveitis and HLAB27 positive or negative control subjects. CONCLUSIONS: We found rs11594656 and rs12722495 to be associated with intermediate uveitis but not with HLAB27 acute anterior uveitis. The genetic heterogeneity found at the IL2RA locus could help explain patterns of concomitance with other autoimmune diseases. PMID- 26133379 TI - Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: the VTEval Project. AB - INTRODUCTION: Venous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date. METHODS AND ANALYSIS: The VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three 'all-comer' studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings. ETHICS AND DISSEMINATION: The VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBER: NCT02156401. PMID- 26133382 TI - Are administrative data valid when measuring patient safety in hospitals? A comparison of data collection methods using a chart review and administrative data. AB - OBJECTIVE: To evaluate the validity and reliability of German Diagnosis Related Group administrative data to measure indicators of patient safety in comparison to clinical records. DESIGN: A cross-sectional study was conducted using chart review (CR) as gold standard and screening of associated administrative data based on DRG coding. SETTING: Three German somatic acute care hospitals for adults. PARTICIPANTS: A total of 3000 cases treated between May and December, 2010. MAIN OUTCOME MEASURES: Eight indicators were used to analyse the incidence of associated adverse events (AEs): pressure ulcers, catheter-related infections, respiratory failure, deep vein thromboses, hospital-acquired pneumonia, acute renal failure, acute myocardial infarction and wound infections. We calculated sensitivity, specificity, positive predictive value (PPV) and Cohen's Kappa with 95% confidence intervals. RESULTS: Screening of administrative data identified 171 AEs and 456 were identified by CR. A number of 135 identical events were identified by both methods. Sensitivities for the detection of AEs using administrative data ranged from 6 to 100%. Specificities ranged from 99 to 100%. PPV were 33 to 100% and reliabilities were 12 to 85%. CONCLUSIONS: Indicators based on German administrative data deviate widely from indicators based on clinical data. Therefore, hospitals should be cautious to use indicators based on administrative data for quality assurance. However, some might be useful for case findings and quality improvement. The precision of the evaluated indicators needs further development to detect AEs by the valid use of administrative data. PMID- 26133383 TI - Dynactin-dependent cortical dynein and spherical spindle shape correlate temporally with meiotic spindle rotation in Caenorhabditis elegans. AB - Oocyte meiotic spindles orient with one pole juxtaposed to the cortex to facilitate extrusion of chromosomes into polar bodies. In Caenorhabditis elegans, these acentriolar spindles initially orient parallel to the cortex and then rotate to the perpendicular orientation. To understand the mechanism of spindle rotation, we characterized events that correlated temporally with rotation, including shortening of the spindle in the pole-to pole axis, which resulted in a nearly spherical spindle at rotation. By analyzing large spindles of polyploid C. elegans and a related nematode species, we found that spindle rotation initiated at a defined spherical shape rather than at a defined spindle length. In addition, dynein accumulated on the cortex just before rotation, and microtubules grew from the spindle with plus ends outward during rotation. Dynactin depletion prevented accumulation of dynein on the cortex and prevented spindle rotation independently of effects on spindle shape. These results support a cortical pulling model in which spindle shape might facilitate rotation because a sphere can rotate without deforming the adjacent elastic cytoplasm. We also present evidence that activation of spindle rotation is promoted by dephosphorylation of the basic domain of p150 dynactin. PMID- 26133384 TI - Proteomic identification of novel cytoskeletal proteins associated with TbPLK, an essential regulator of cell morphogenesis in Trypanosoma brucei. AB - Trypanosoma brucei is the causative agent of African sleeping sickness, a devastating disease endemic to sub-Saharan Africa with few effective treatment options. The parasite is highly polarized, including a single flagellum that is nucleated at the posterior of the cell and adhered along the cell surface. These features are essential and must be transmitted to the daughter cells during division. Recently we identified the T. brucei homologue of polo-like kinase (TbPLK) as an essential morphogenic regulator. In the present work, we conduct proteomic screens to identify potential TbPLK binding partners and substrates to better understand the molecular mechanisms of kinase function. These screens identify a cohort of proteins, most of which are completely uncharacterized, which localize to key cytoskeletal organelles involved in establishing cell morphology, including the flagella connector, flagellum attachment zone, and bilobe structure. Depletion of these proteins causes substantial changes in cell division, including mispositioning of the kinetoplast, loss of flagellar connection, and prevention of cytokinesis. The proteins identified in these screens provide the foundation for establishing the molecular networks through which TbPLK directs cell morphogenesis in T. brucei. PMID- 26133385 TI - Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition. AB - Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target. PMID- 26133387 TI - Magnetically Targeted Stem Cell Delivery for Regenerative Medicine. AB - Stem cells play a special role in the body as agents of self-renewal and auto reparation for tissues and organs. Stem cell therapies represent a promising alternative strategy to regenerate damaged tissue when natural repairing and conventional pharmacological intervention fail to do so. A fundamental impediment for the evolution of stem cell therapies has been the difficulty of effectively targeting administered stem cells to the disease foci. Biocompatible magnetically responsive nanoparticles are being utilized for the targeted delivery of stem cells in order to enhance their retention in the desired treatment site. This noninvasive treatment-localization strategy has shown promising results and has the potential to mitigate the problem of poor long-term stem cell engraftment in a number of organ systems post-delivery. In addition, these same nanoparticles can be used to track and monitor the cells in vivo, using magnetic resonance imaging. In the present review we underline the principles of magnetic targeting for stem cell delivery, with a look at the logic behind magnetic nanoparticle systems, their manufacturing and design variants, and their applications in various pathological models. PMID- 26133388 TI - Increased Risk of Leukemia After Radioactive Iodine Therapy in Patients with Thyroid Cancer: A Nationwide, Population-Based Study in Korea. AB - BACKGROUND: The use of radioactive iodine therapy (RAIT) is increasing in thyroid cancer management. The association between RAIT at high doses and leukemia is well known, but studies of this association in a large population are lacking. This study aims to investigate the association between RAIT and leukemia in the context of current practice. METHODS: Retrospective analysis of a 542,845 person year (PY) follow-up of thyroid cancer patients was conducted using the Korean National Health Insurance claims database between January 2008 and December 2013. Patients were categorized according to RAIT dose (no RAI; low dose, <=30 mCi; moderate dose, 31-100 mCi; high dose, 101-150 mCi; and very high dose, >150 mCi). RESULTS: Among 211,360 thyroid cancer patients, 72 (0.03%) patients developed leukemia during follow-up (median 877 days). The cumulative incidence of leukemia per 10(5) person-year (PY) was 9.8 in the no RAI [95% confidence interval (CI) 6.4-14.4]; 6.1 [CI 1.7-15.7] in the low-dose; 8.6 [CI 3.2-18.7] in the moderate dose; 29.5 [CI 18.3-45.1] in the high-dose; and 20.9 [CI 11.7-34.4] in the very high-dose groups. The hazard ratios were elevated significantly in the high- and very high-dose groups (HR 3.1 and 2.1, respectively, p<0.001) when compared with the no RAI group. CONCLUSIONS: RAIT exceeding 100 mCi was strongly associated with the development of leukemia in a nationwide, population-based study, while lower RAIT doses were not. Considering the favorable survival of patients with thyroid cancer and the potential harm of RAIT, physicians need to consider the pros and cons of RAIT when using this treatment option. PMID- 26133386 TI - Medical Textiles as Vascular Implants and Their Success to Mimic Natural Arteries. AB - Vascular implants belong to a specialised class of medical textiles. The basic purpose of a vascular implant (graft and stent) is to act as an artificial conduit or substitute for a diseased artery. However, the long-term healing function depends on its ability to mimic the mechanical and biological behaviour of the artery. This requires a thorough understanding of the structure and function of an artery, which can then be translated into a synthetic structure based on the capabilities of the manufacturing method utilised. Common textile manufacturing techniques, such as weaving, knitting, braiding, and electrospinning, are frequently used to design vascular implants for research and commercial purposes for the past decades. However, the ability to match attributes of a vascular substitute to those of a native artery still remains a challenge. The synthetic implants have been found to cause disturbance in biological, biomechanical, and hemodynamic parameters at the implant site, which has been widely attributed to their structural design. In this work, we reviewed the design aspect of textile vascular implants and compared them to the structure of a natural artery as a basis for assessing the level of success as an implant. The outcome of this work is expected to encourage future design strategies for developing improved long lasting vascular implants. PMID- 26133389 TI - Quest for Orthologs Entails Quest for Tree of Life: In Search of the Gene Stream. AB - Quest for Orthologs (QfO) is a community effort with the goal to improve and benchmark orthology predictions. As quality assessment assumes prior knowledge on species phylogenies, we investigated the congruency between existing species trees by comparing the relationships of 147 QfO reference organisms from six Tree of Life (ToL)/species tree projects: The National Center for Biotechnology Information (NCBI) taxonomy, Opentree of Life, the sequenced species/species ToL, the 16S ribosomal RNA (rRNA) database, and trees published by Ciccarelli et al. (Ciccarelli FD, et al. 2006. Toward automatic reconstruction of a highly resolved tree of life. Science 311:1283-1287) and by Huerta-Cepas et al. (Huerta-Cepas J, Marcet-Houben M, Gabaldon T. 2014. A nested phylogenetic reconstruction approach provides scalable resolution in the eukaryotic Tree Of Life. PeerJ PrePrints 2:223) Our study reveals that each species tree suggests a different phylogeny: 87 of the 146 (60%) possible splits of a dichotomous and rooted tree are congruent, while all other splits are incongruent in at least one of the species trees. Topological differences are observed not only at deep speciation events, but also within younger clades, such as Hominidae, Rodentia, Laurasiatheria, or rosids. The evolutionary relationships of 27 archaea and bacteria are highly inconsistent. By assessing 458,108 gene trees from 65 genomes, we show that consistent species topologies are more often supported by gene phylogenies than contradicting ones. The largest concordant species tree includes 77 of the QfO reference organisms at the most. Results are summarized in the form of a consensus ToL (http://swisstree.vital-it.ch/species_tree) that can serve different benchmarking purposes. PMID- 26133391 TI - Suppression of KLF8 induces cell differentiation and sensitizes colorectal cancer to 5-fluorouracil. AB - KLF8 is a member of the KLF transcription factor family that plays an important role in oncogenesis. However, the role of KLF8 in colorectal cancer remains unknown. The aims of the present study were to examine KLF8 expression in colorectal cancers, to determine the role of KLF8 in cell differentiation and to investigate the antiproliferative effect of KLF8 silencing. The expression of KLF8 and phospho-ERK proteins was analyzed, and the effects of KLF8 suppression on cell differentiation and growth were evaluated. In addition, the biological impact of KLF8 knockdown on colorectal cancer cells was investigated in vitro and in vivo. The expression of the KLF8 protein was higher in 10/14 (71.43%) fresh cancer tissues compared with adjacent normal tissues, and the blockade of ERK signaling by U0126 decreased the expression of KLF8 in a time- and dose-dependent manner. Furthermore, KLF8-siRNA induced the expression of carcinoembryonic antigen (CEA) and E-cadherin as well as the maturation of F-actin. KLF8 suppression inhibited serum-dependent, anchorage-dependent and -independent cell growth. Moreover, KLF8 silencing induced apoptosis and sensitized cancer cells to 5-fluorouracil (5-FU). A strong antitumorigenic effect by lenti-KLF8-shRNA, which was enhanced when combined with 5-FU treatment, was exerted in nude mice. Thus, KLF8 suppression induced cell differentiation and inhibited tumorigenesis. PMID- 26133390 TI - A Novel Terminal-Repeat Retrotransposon in Miniature (TRIM) Is Massively Expressed in Echinococcus multilocularis Stem Cells. AB - Taeniid cestodes (including the human parasites Echinococcus spp. and Taenia solium) have very few mobile genetic elements (MGEs) in their genome, despite lacking a canonical PIWI pathway. The MGEs of these parasites are virtually unexplored, and nothing is known about their expression and silencing. In this work, we report the discovery of a novel family of small nonautonomous long terminal repeat retrotransposons (also known as terminal-repeat retrotransposons in miniature, TRIMs) which we have named ta-TRIM (taeniid TRIM). ta-TRIMs are only the second family of TRIM elements discovered in animals, and are likely the result of convergent reductive evolution in different taxonomic groups. These elements originated at the base of the taeniid tree and have expanded during taeniid diversification, including after the divergence of closely related species such as Echinococcus multilocularis and Echinococcus granulosus. They are massively expressed in larval stages, from a small proportion of full-length copies and from isolated terminal repeats that show transcriptional read-through into downstream regions, generating novel noncoding RNAs and transcriptional fusions to coding genes. In E. multilocularis, ta-TRIMs are specifically expressed in the germinative cells (the somatic stem cells) during asexual reproduction of metacestode larvae. This would provide a developmental mechanism for insertion of ta-TRIMs into cells that will eventually generate the adult germ line. Future studies of active and inactive ta-TRIM elements could give the first clues on MGE silencing mechanisms in cestodes. PMID- 26133392 TI - Quality of life assessment in cosmetics: specificity and interest of the international BeautyQol instrument. AB - The wide use of cosmetics and their perceived benefits upon well-being imply objective descriptions of their effects upon the different dimensions contributing to the quality of life (QoL). Such a goal pleas for using relevant and validated scientific instruments with robust measurement methods. This paper discusses the interest of the new validated questionnaire BeautyQoL specifically designed to assess the effect of cosmetic products on physical appearance and QoL. After conducting a review of skin appearance and QoL, three phases of the international codevelopment have been carried out in the following sequence: semi directed interviews (Phase 1), acceptability study (Phase 2), and validation study (Phase 3). Data collection and validation process have been carried out in 16 languages. This review confirms that QoL instruments developed in dermatology are not suitable to assess cosmetic products, mainly because of their lack of sensitivity. General acceptability of BeautyQol was very good. Forty-two questions have been structured in five dimensions that explained 76.7% of the total variance: Social Life, Self-confidence, Mood, Vitality, and Attractiveness. Cronbach's alpha coefficients are between 0.932 and 0.978, confirming the good internal consistency of the results. The BeautyQol questionnaire is the first international instrument specific to cosmetic products and physical appearance that has been validated in 16 languages and could be used in a number of clinical trials and descriptive studies to demonstrate the added value of these products on the QoL. PMID- 26133395 TI - Enhanced electrical conductivity and hardness of silver-nickel composites by silver-coated multi-walled carbon nanotubes. AB - We investigated electrical conductivity and Vickers hardness of Ag- and Ni-based composites prepared by powder metallurgy involving spark plasma sintering. The starting composition was Ag:Ni = 61:39 vol%, which provided an electrical conductivity of 3.30 * 10(5) S cm(-1) and a hardness of 1.27 GPa. The addition of bare multi-walled carbon nanotubes (MWNTs, 1.45 vol%) increased hardness (1.31 GPa) but decreased electrical conductivity (2.99 * 10(5) S cm(-1)) and carrier mobility (11 cm(2) V(-1) s(-1)) due to the formation of Ni3C in the interface between the MWNTs and Ni during spark plasma sintering. The formation of Ni3C was prevented by coating the surface of the nanotubes with Ag (nAgMWNTs), concomitantly increasing electrical conductivity (3.43 * 10(5) S cm(-1)) and hardness (1.37 GPa) of the sintered specimen (Ag:Ni:nAgMWNTs = 59.55:39:1.45 vol%). The electrical contact switching time (133 357) was also increased by 30%, demonstrating excellent feasibility as electrical contact materials for electric power industries. PMID- 26133393 TI - Aortic dilation, genetic testing, and associated diagnoses. AB - PURPOSE: The aims of this study were to determine the genetic diagnoses most frequently associated with aortic dilation in a large population and to describe the results of genetic testing in the same. METHODS: A retrospective review of records from patients with known aortic dilation identified through an echocardiogram database was performed. During the study period, different chromosomal microarray platforms and molecular diagnostic techniques were used. RESULTS: A total of 715 patients (mean age, 9.7 years; 67% male) met study inclusion criteria. The overall frequency of underlying presumptive or confirmed genetic diagnoses was 17% (125/715). Molecular evaluation for possible underlying aortopathy-related disorders was performed in 9% of patients (66/715). Next generation sequencing panels were performed in 16 patients, and pathogenic abnormalities were detected in 4 (25%). Microarrays were conducted in 10% of patients (72/715), with a total of 23 pathogenic copy-number variants identified in 19 patients (26%). Marfan syndrome was the most frequently recognized genetic disorder associated with aortic dilation, but other cytogenetic abnormalities and associated diagnoses also were identified. CONCLUSION: The differential diagnosis in patients with aortic dilation is broad and includes many conditions outside the common connective tissue disorder spectrum. A genetics evaluation should be considered to assist in the diagnostic evaluation.Genet Med 18 4, 356-363. PMID- 26133394 TI - POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. AB - PURPOSE: Germ-line mutations in the exonuclease domains of POLE and POLD1 have been recently associated with polyposis and colorectal cancer (CRC) predisposition. Here, we aimed to gain a better understanding of the phenotypic characteristics of this syndrome to establish specific criteria for POLE and POLD1 mutation screening and to help define the clinical management of mutation carriers. METHODS: The exonuclease domains of POLE and POLD1 were studied in 529 kindred, 441 with familial nonpolyposis CRC and 88 with polyposis, by using pooled DNA amplification and massively parallel sequencing. RESULTS: Seven novel or rare genetic variants were identified. In addition to the POLE p.L424V recurrent mutation in a patient with polyposis, CRC and oligodendroglioma, six novel or rare POLD1 variants (four of them, p.D316H, p.D316G, p.R409W, and p.L474P, with strong evidence for pathogenicity) were identified in nonpolyposis CRC families. Phenotypic data from these and previously reported POLE/POLD1 carriers point to an associated phenotype characterized by attenuated or oligo adenomatous colorectal polyposis, CRC, and probably brain tumors. In addition, POLD1 mutations predispose to endometrial and breast tumors. CONCLUSION: Our results widen the phenotypic spectrum of the POLE/POLD1-associated syndrome and identify novel pathogenic variants. We propose guidelines for genetic testing and surveillance recommendations.Genet Med 18 4, 325-332. PMID- 26133396 TI - Recent advances and future applications of microfluidic live-cell microarrays. AB - Microfluidic live-cell microarrays show much promise as screening tools for biomedical research because they could shed light on key biological processes such as cell signaling and cell-to-cell and cell-to-substrate dynamic responses. While miniaturization reduces the need for expensive clinical grade reagents, the integration of functional components including micropumps, biosensors, actuators, mixers and gradient generators results in improved assay reliability, reproducibility and well-defined cell culture conditions. The present review addresses recent technological advances in microfluidic live-cell microarray technology with a special focus on the applications of microfluidic single-cell, multi-cell and 3D cell microarrays. PMID- 26133398 TI - Cell and protein compatible 3D bioprinting of mechanically strong constructs for bone repair. AB - Rapid prototyping of bone tissue engineering constructs often utilizes elevated temperatures, organic solvents and/or UV light for materials processing. These harsh conditions may prevent the incorporation of cells and therapeutic proteins in the fabrication processes. Here we developed a method for using bioprinting to produce constructs from a thermoresponsive microparticulate material based on poly(lactic-co-glycolic acid) at ambient conditions. These constructs could be engineered with yield stresses of up to 1.22 MPa and Young's moduli of up to 57.3 MPa which are within the range of properties of human cancellous bone. Further study showed that protein-releasing microspheres could be incorporated into the bioprinted constructs. The release of the model protein lysozyme from bioprinted constructs was sustainted for a period of 15 days and a high degree of protein activity could be measured up to day 9. This work suggests that bioprinting is a viable route to the production of mechanically strong constructs for bone repair under mild conditions which allow the inclusion of viable cells and active proteins. PMID- 26133397 TI - Resistance of R-Ras knockout mice to skin tumour induction. AB - The R-ras gene encodes a small GTPase that is a member of the Ras family. Despite close sequence similarities, R-Ras is functionally distinct from the prototypic Ras proteins; no transformative activity and no activating mutations of R-Ras in human malignancies have been reported for it. R-Ras activity appears inhibitory towards tumour proliferation and invasion, and to promote cellular quiescence. Contrary to this, using mice with a deletion of the R-ras gene, we found that R Ras facilitates DMBA/TPA-induced skin tumour induction. The tumours appeared in wild-type (WT) mice on average 6 weeks earlier than in R-Ras knockout (R-Ras KO) mice. WT mice developed almost 6 times more tumours than R-Ras KO mice. Despite strong R-Ras protein expression in the dermal blood vessels, no R-Ras could be detected in the epidermis from where the tumours arose. The DMBA/TPA skin tumourigenesis-model is highly dependent upon inflammation, and we found a greatly attenuated skin inflammatory response to DMBA/TPA-treatment in the R-Ras KO mice in the context of leukocyte infiltration and proinflammatory cytokine expression. Thus, these data suggest that despite its characterised role in promoting cellular quiescence, R-Ras is pro-tumourigenic in the DMBA/TPA tumour model and important for the inflammatory response to DMBA/TPA treatment. PMID- 26133399 TI - Evaluation of seamless ligation cloning extract preparation methods from an Escherichia coli laboratory strain. AB - Seamless ligation cloning extract (SLiCE) is a simple and efficient method for DNA cloning without the use of restriction enzymes. Instead, SLiCE uses homologous recombination activities from Escherichia coli cell lysates. To date, SLiCE preparation has been performed using an expensive commercially available lytic reagent. To expand the utility of the SLiCE method, we evaluated different methods for SLiCE preparation that avoid using this reagent. Consequently, cell extracts prepared with buffers containing Triton X-100, which is a common and low cost nonionic detergent, exhibited sufficient cloning activity for seamless gene incorporation into a vector. PMID- 26133400 TI - Perspective: Treating electron over-delocalization with the DFT+U method. AB - Many people in the materials science and solid-state community are familiar with the acronym "DFT+U." For those less familiar, this technique uses ideas from model Hamiltonians that permit the description of both metals and insulators to address problems of electron over-delocalization in practical implementations of density functional theory (DFT). Exchange-correlation functionals in DFT are often described as belonging to a hierarchical "Jacob's ladder" of increasing accuracy in moving from local to non-local descriptions of exchange and correlation. DFT+U is not on this "ladder" but rather acts as an "elevator" because it systematically tunes relative energetics, typically on a localized subshell (e.g., d or f electrons), regardless of the underlying functional employed. However, this tuning is based on a metric of the local electron density of the subshells being addressed, thus necessitating physical or chemical or intuition about the system of interest. I will provide a brief overview of the history of how DFT+U came to be starting from the origin of the Hubbard and Anderson model Hamiltonians. This history lesson is necessary because it permits us to make the connections between the "Hubbard U" and fundamental outstanding challenges in electronic structure theory, and it helps to explain why this method is so widely applied to transition-metal oxides and organometallic complexes alike. PMID- 26133401 TI - Communication: State-to-state dynamics of the Cl + H2O -> HCl + OH reaction: Energy flow into reaction coordinate and transition-state control of product energy disposal. AB - Quantum state-to-state dynamics of a prototypical four-atom reaction, namely, Cl + H2O -> HCl + OH, is investigated for the first time in full dimensionality using a transition-state wave packet method. The state-to-state reactivity and its dependence on the reactant internal excitations are analyzed and found to share many similarities both energetically and dynamically with the H + H2O -> H2 + OH reaction. The strong enhancement of reactivity by the H2O stretching vibrational excitations in both reactions is attributed to the favorable energy flow into the reaction coordinate near the transition state. On the other hand, the insensitivity of the product state distributions with regard to reactant internal excitation stems apparently from the transition-state control of product energy disposal. PMID- 26133402 TI - Communication: Rotational excitation of HCl by H: Rigid rotor vs. reactive approaches. AB - We report fully quantum time-independent calculations of cross sections for the collisional excitation of HCl by H, an astrophysically relevant process. Our calculations are based on the Bian-Werner ClH2 potential energy surface and include the possibility of HCl destruction through reactive collisions. The strongest collision-induced rotational HCl transitions are those with Deltaj = 1, and the magnitude of the HCl-H inelastic cross sections is of the same order of magnitude as the HCl-H2 ones. Results of exact calculations, i.e., including the reactive channels, are compared to pure inelastic calculations based on the rigid rotor approximation. A very good agreement is found between the two approaches over the whole energy range 10-3000 cm(-1). At the highest collisional energies, where the reaction takes place, the rigid rotor approach slightly overestimates the cross sections, as expected. Hence, the rigid rotor approach is found to be reliable at interstellar temperatures. PMID- 26133403 TI - Communication: Direct tests of single-parameter aging. AB - This paper presents accurate data for the physical aging of organic glasses just below the glass transition probed by monitoring the following quantities after temperature up and down jumps: the shear-mechanical resonance frequency (~360 kHz), the dielectric loss at 1 Hz, the real part of the dielectric constant at 10 kHz, and the loss-peak frequency of the dielectric beta process (~10 kHz). The setup used allows for keeping temperature constant within 100 MUK and for thermal equilibration within a few seconds after a temperature jump. The data conform to a new simplified version of the classical Tool-Narayanaswamy aging formalism, which makes it possible to calculate one relaxation curve directly from another without any fitting to analytical functions. PMID- 26133404 TI - A systematic benchmark of the ab initio Bethe-Salpeter equation approach for low lying optical excitations of small organic molecules. AB - The predictive power of the ab initio Bethe-Salpeter equation (BSE) approach, rigorously based on many-body Green's function theory but incorporating information from density functional theory, has already been demonstrated for the optical gaps and spectra of solid-state systems. Interest in photoactive hybrid organic/inorganic systems has recently increased and so has the use of the BSE for computing neutral excitations of organic molecules. However, no systematic benchmarks of the BSE for neutral electronic excitations of organic molecules exist. Here, we study the performance of the BSE for the 28 small molecules in Thiel's widely used time-dependent density functional theory benchmark set [Schreiber et al., J. Chem. Phys. 128, 134110 (2008)]. We observe that the BSE produces results that depend critically on the mean-field starting point employed in the perturbative approach. We find that this starting point dependence is mainly introduced through the quasiparticle energies obtained at the intermediate GW step and that with a judicious choice of starting mean-field, singlet excitation energies obtained from BSE are in excellent quantitative agreement with higher-level wavefunction methods. The quality of the triplet excitations is slightly less satisfactory. PMID- 26133405 TI - A generalized Derjaguin approximation for electrical-double-layer interactions at arbitrary separations. AB - Derjaguin's approximation provides the electrical-double-layer interaction force between two arbitrary convex surfaces as the product of the corresponding one dimensional parallel-plate interaction potential and an effective radius R (function of the radii of curvature and relative orientation of the two surfaces at minimum separation). The approximation holds when both the Debye length 1/kappa and minimum separation h are small compared to R. We show here that a simple transformation, R=>[R]?[[K1][K2]/K1K2], yields an approximation uniformly valid for arbitrary separations h; here, Ki is the Gaussian curvature of particle i at minimum separation, and [ ? ] is an operator which adds h/2 to all radii of curvature present in the expression on which it acts. We derive this result in two steps. First, we extend the two-dimensional ray-theory analysis of Schnitzer [Phys. Rev. E 91, 022307 (2015)], valid for kappah, kappaR ? 1, to three dimensions. We thereby obtain a general closed form expression for the force by matching nonlinear diffuse-charge boundary layers with a WKBJ-type expansion describing the bulk potential, and subsequent integration via Laplace's method of the traction over the medial surface generated by all spheres maximally inscribed between the two surfaces. Second, we exploit the existence of an overlap domain, 1 ? kappah ? kappaR, where both the ray-theory and the Derjaguin approximations hold, to systematically form the generalized mapping. The validity of the result is demonstrated by comparison with numerical computations. PMID- 26133406 TI - Transition matrices and orbitals from reduced density matrix theory. AB - In this contribution, we report two different methodologies for characterizing the electronic structure reorganization occurring when a chromophore undergoes an electronic transition. For the first method, we start by setting the theoretical background necessary to the reinterpretation through simple tensor analysis of (i) the transition density matrix and (ii) the natural transition orbitals in the scope of reduced density matrix theory. This novel interpretation is made more clear thanks to a short compendium of the one-particle reduced density matrix theory in a Fock space. The formalism is further applied to two different classes of excited states calculation methods, both requiring a single-determinant reference, that express an excited state as a hole-particle mono-excited configurations expansion, to which particle-hole correlation is coupled (time dependent Hartree-Fock/time-dependent density functional theory) or not (configuration interaction single/Tamm-Dancoff approximation). For the second methodology presented in this paper, we introduce a novel and complementary concept related to electronic transitions with the canonical transition density matrix and the canonical transition orbitals. Their expression actually reflects the electronic cloud polarisation in the orbital space with a decomposition based on the actual contribution of one-particle excitations from occupied canonical orbitals to virtual ones. This approach validates our novel interpretation of the transition density matrix elements in terms of the Euclidean norm of elementary transition vectors in a linear tensor space. A proper use of these new concepts leads to the conclusion that despite the different principles underlying their construction, they provide two equivalent excited states topological analyses. This connexion is evidenced through simple illustrations of (in)organic dyes electronic transitions analysis. PMID- 26133407 TI - Selection of active spaces for multiconfigurational wavefunctions. AB - The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F2, ozone, and NO2), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr2). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions are discussed: finding the UHF solutions, discontinuities on potential energy surfaces, and inclusion of dynamical electron correlation and generalization to excited states. PMID- 26133408 TI - Photoelectron circular dichroism in the multiphoton ionization by short laser pulses. I. Propagation of single-active-electron wave packets in chiral pseudo potentials. AB - A theoretical method to study the angle-resolved multiphoton ionization of polyatomic molecules is developed. It is based on the time-dependent formulation of the Single Center (TDSC) method and consists in the propagation of single active-electron wave packets in the effective molecular potentials in the presence of intense laser pulses. For this purpose, the time-dependent Schrodinger equation for one electron, moving in a molecular field and interacting with an arbitrary laser pulse, is solved in spherical coordinates by an efficient numerical approach. As a test, the method is applied to the one- and two-photon ionizations of a model methane-like chiral system by circularly polarized short intense high-frequency laser pulses. Thereby, we analyze the photoelectron circular dichroism (PECD) in the momentum distribution. The considered model application illustrates the capability of the TDSC method to study multiphoton PECD in fixed-in-space and randomly oriented chiral molecules. PMID- 26133409 TI - On the rejection-based algorithm for simulation and analysis of large-scale reaction networks. AB - Stochastic simulation for in silico studies of large biochemical networks requires a great amount of computational time. We recently proposed a new exact simulation algorithm, called the rejection-based stochastic simulation algorithm (RSSA) [Thanh et al., J. Chem. Phys. 141(13), 134116 (2014)], to improve simulation performance by postponing and collapsing as much as possible the propensity updates. In this paper, we analyze the performance of this algorithm in detail, and improve it for simulating large-scale biochemical reaction networks. We also present a new algorithm, called simultaneous RSSA (SRSSA), which generates many independent trajectories simultaneously for the analysis of the biochemical behavior. SRSSA improves simulation performance by utilizing a single data structure across simulations to select reaction firings and forming trajectories. The memory requirement for building and storing the data structure is thus independent of the number of trajectories. The updating of the data structure when needed is performed collectively in a single operation across the simulations. The trajectories generated by SRSSA are exact and independent of each other by exploiting the rejection-based mechanism. We test our new improvement on real biological systems with a wide range of reaction networks to demonstrate its applicability and efficiency. PMID- 26133410 TI - Linear transformation of anharmonic molecular force constants between normal and Cartesian coordinates. AB - A full derivation of the analytic transformation of the quadratic, cubic, and quartic force constants from normal coordinates to Cartesian coordinates is given. Previous attempts at this transformation have resulted in non-linear transformations; however, for the first time, a simple linear transformation is presented here. Two different approaches have been formulated and implemented, one of which does not require prior knowledge of the translation-rotation eigenvectors from diagonalization of the Hessian matrix. The validity of this method is tested using two molecules H2O and c-C3H2D(+). PMID- 26133411 TI - Self-consistent Kohn-Sham method based on the adiabatic-connection fluctuation dissipation theorem and the exact-exchange kernel. AB - A self-consistent Kohn-Sham method based on the adiabatic-connection fluctuation dissipation (ACFD) theorem, employing the frequency-dependent exact exchange kernel fx is presented. The resulting SC-exact-exchange-only (EXX)-ACFD method leads to even more accurate correlation potentials than those obtained within the direct random phase approximation (dRPA). In contrast to dRPA methods, not only the Coulomb kernel but also the exact exchange kernel fx is taken into account in the EXX-ACFD correlation which results in a method that, unlike dRPA methods, is free of self-correlations, i.e., a method that treats exactly all one-electron systems, like, e.g., the hydrogen atom. The self-consistent evaluation of EXX ACFD total energies improves the accuracy compared to EXX-ACFD total energies evaluated non-self-consistently with EXX or dRPA orbitals and eigenvalues. Reaction energies of a set of small molecules, for which highly accurate experimental reference data are available, are calculated and compared to quantum chemistry methods like Moller-Plesset perturbation theory of second order (MP2) or coupled cluster methods [CCSD, coupled cluster singles, doubles, and perturbative triples (CCSD(T))]. Moreover, we compare our methods to other ACFD variants like dRPA combined with perturbative corrections such as the second order screened exchange corrections or a renormalized singles correction. Similarly, the performance of our EXX-ACFD methods is investigated for the non covalently bonded dimers of the S22 reference set and for potential energy curves of noble gas, water, and benzene dimers. The computational effort of the SC-EXX ACFD method exhibits the same scaling of N(5) with respect to the system size N as the non-self-consistent evaluation of only the EXX-ACFD correlation energy; however, the prefactor increases significantly. Reaction energies from the SC-EXX ACFD method deviate quite little from EXX-ACFD energies obtained non-self consistently with dRPA orbitals and eigenvalues, and the deviation reduces even further if the Coulomb kernel is scaled by a factor of 0.75 in the dRPA to reduce self-correlations in the dRPA correlation potential. For larger systems, such a non-self-consistent EXX-ACFD method is a competitive alternative to high-level wave-function-based methods, yielding higher accuracy than MP2 and CCSD methods while exhibiting a better scaling of the computational effort than CCSD or CCSD(T) methods. Moreover, EXX-ACFD methods were shown to be applicable in situation characterized by static correlation. PMID- 26133412 TI - The multi-configurational time-dependent Hartree approach revisited. AB - The multi-configurational time-dependent Hartree (MCTDH) approach facilitates accurate high-dimensional quantum dynamics simulations. In the approach, the wavefunction is expanded in a direct product of self-adapting time-dependent single-particle functions (SPFs). The equations of motion for the expansion coefficients and the SPFs are obtained via the Dirac-Frenkel variational principle. While this derivation yields well-defined differential equations for the motion of occupied SPFs, singularities in the working equations resulting from unoccupied SPFs have to be removed by a regularization procedure. Here, an alternative derivation of the MCTDH equations of motion is presented. It employs an analysis of the time-dependence of the single-particle density matrices up to second order. While the analysis of the first order terms yields the known equations of motion for the occupied SPFs, the analysis of the second order terms provides new equations which allow one to identify optimal choices for the unoccupied SPFs. The effect of the optimal choice of the unoccupied SPFs on the structure of the MCTDH equations of motion and their regularization is discussed. Generalized equations applicable in the multi-layer MCTDH framework are presented. Finally, the effects resulting from the initial choice of the unoccupied SPFs are illustrated by a simple numerical example. PMID- 26133413 TI - Parametrizing linear generalized Langevin dynamics from explicit molecular dynamics simulations. AB - Fundamental understanding of complex dynamics in many-particle systems on the atomistic level is of utmost importance. Often the systems of interest are of macroscopic size but can be partitioned into a few important degrees of freedom which are treated most accurately and others which constitute a thermal bath. Particular attention in this respect attracts the linear generalized Langevin equation, which can be rigorously derived by means of a linear projection technique. Within this framework, a complicated interaction with the bath can be reduced to a single memory kernel. This memory kernel in turn is parametrized for a particular system studied, usually by means of time-domain methods based on explicit molecular dynamics data. Here, we discuss that this task is more naturally achieved in frequency domain and develop a Fourier-based parametrization method that outperforms its time-domain analogues. Very surprisingly, the widely used rigid bond method turns out to be inappropriate in general. Importantly, we show that the rigid bond approach leads to a systematic overestimation of relaxation times, unless the system under study consists of a harmonic bath bi-linearly coupled to the relevant degrees of freedom. PMID- 26133414 TI - Beyond the electric-dipole approximation: A formulation and implementation of molecular response theory for the description of absorption of electromagnetic field radiation. AB - We present a formulation of molecular response theory for the description of a quantum mechanical molecular system in the presence of a weak, monochromatic, linearly polarized electromagnetic field without introducing truncated multipolar expansions. The presentation focuses on a description of linear absorption by adopting the energy-loss approach in combination with the complex polarization propagator formulation of response theory. Going beyond the electric-dipole approximation is essential whenever studying electric-dipole-forbidden transitions, and in general, non-dipolar effects become increasingly important when addressing spectroscopies involving higher-energy photons. These two aspects are examined by our study of the near K-edge X-ray absorption fine structure of the alkaline earth metals (Mg, Ca, Sr, Ba, and Ra) as well as the trans-polyenes. In following the series of alkaline earth metals, the sizes of non-dipolar effects are probed with respect to increasing photon energies and a detailed assessment of results is made in terms of studying the pertinent transition electron densities and in particular their spatial extension in comparison with the photon wavelength. Along the series of trans-polyenes, the sizes of non dipolar effects are probed for X-ray spectroscopies on organic molecules with respect to the spatial extension of the chromophore. PMID- 26133415 TI - A new class of ensemble conserving algorithms for approximate quantum dynamics: Theoretical formulation and model problems. AB - We develop two classes of quasi-classical dynamics that are shown to conserve the initial quantum ensemble when used in combination with the Feynman-Kleinert approximation of the density operator. These dynamics are used to improve the Feynman-Kleinert implementation of the classical Wigner approximation for the evaluation of quantum time correlation functions known as Feynman-Kleinert linearized path-integral. As shown, both classes of dynamics are able to recover the exact classical and high temperature limits of the quantum time correlation function, while a subset is able to recover the exact harmonic limit. A comparison of the approximate quantum time correlation functions obtained from both classes of dynamics is made with the exact results for the challenging model problems of the quartic and double-well potentials. It is found that these dynamics provide a great improvement over the classical Wigner approximation, in which purely classical dynamics are used. In a special case, our first method becomes identical to centroid molecular dynamics. PMID- 26133416 TI - Application of a new ensemble conserving quantum dynamics simulation algorithm to liquid para-hydrogen and ortho-deuterium. AB - We apply the Feynman-Kleinert Quasi-Classical Wigner (FK-QCW) method developed in our previous work [Smith et al., J. Chem. Phys. 142, 244112 (2015)] for the determination of the dynamic structure factor of liquid para-hydrogen and ortho deuterium at state points of (T = 20.0 K, n = 21.24 nm(-3)) and (T = 23.0 K, n = 24.61 nm(-3)), respectively. When applied to this challenging system, it is shown that this new FK-QCW method consistently reproduces the experimental dynamic structure factor reported by Smith et al. [J. Chem. Phys. 140, 034501 (2014)] for all momentum transfers considered. This shows that FK-QCW provides a substantial improvement over the Feynman-Kleinert linearized path-integral method, in which purely classical dynamics are used. Furthermore, for small momentum transfers, it is shown that FK-QCW provides nearly the same results as ring-polymer molecular dynamics (RPMD), thus suggesting that FK-QCW provides a potentially more appealing algorithm than RPMD since it is not formally limited to correlation functions involving linear operators. PMID- 26133417 TI - Computing intramolecular charge and energy transfer rates using optimal modes. AB - In our recent work [X. Yang and E. R. Bittner, J. Phys. Chem. A 118, 5196 (2014)], we showed how to construct a reduced set of nuclear motions that capture the coupling between electronic and nuclear degrees of freedom over the course of an electronic transition. We construct these modes, referred to as "Lanczos modes," by applying a search algorithm to find linear combinations of vibrational normal modes that optimize the electronic/nuclear coupling operator. Here, we analyze the irreducible representations of the dominant contributions of these modes and find that for the cases considered here, these belong to totally symmetric irreducible representations of the donor and acceptor moieties. Upon investigating the molecular geometry changes following the transition, we propose that the electronic transition process can be broken into two steps, in the agreement of Born-Oppenheimer approximation: a fast excitation transfer occurs, facilitated by the "primary Lanczos mode," followed by slow nuclear relaxation on the final electronic diabatic surface. PMID- 26133418 TI - Variance decomposition in stochastic simulators. AB - This work aims at the development of a mathematical and computational approach that enables quantification of the inherent sources of stochasticity and of the corresponding sensitivities in stochastic simulations of chemical reaction networks. The approach is based on reformulating the system dynamics as being generated by independent standardized Poisson processes. This reformulation affords a straightforward identification of individual realizations for the stochastic dynamics of each reaction channel, and consequently a quantitative characterization of the inherent sources of stochasticity in the system. By relying on the Sobol-Hoeffding decomposition, the reformulation enables us to perform an orthogonal decomposition of the solution variance. Thus, by judiciously exploiting the inherent stochasticity of the system, one is able to quantify the variance-based sensitivities associated with individual reaction channels, as well as the importance of channel interactions. Implementation of the algorithms is illustrated in light of simulations of simplified systems, including the birth-death, Schlogl, and Michaelis-Menten models. PMID- 26133419 TI - An EQT-cDFT approach to determine thermodynamic properties of confined fluids. AB - We present a continuum-based approach to predict the structure and thermodynamic properties of confined fluids at multiple length-scales, ranging from a few angstroms to macro-meters. The continuum approach is based on the empirical potential-based quasi-continuum theory (EQT) and classical density functional theory (cDFT). EQT is a simple and fast approach to predict inhomogeneous density and potential profiles of confined fluids. We use EQT potentials to construct a grand potential functional for cDFT. The EQT-cDFT-based grand potential can be used to predict various thermodynamic properties of confined fluids. In this work, we demonstrate the EQT-cDFT approach by simulating Lennard-Jones fluids, namely, methane and argon, confined inside slit-like channels of graphene. We show that the EQT-cDFT can accurately predict the structure and thermodynamic properties, such as density profiles, adsorption, local pressure tensor, surface tension, and solvation force, of confined fluids as compared to the molecular dynamics simulation results. PMID- 26133420 TI - Efficient preconditioning of the electronic structure problem in large scale ab initio molecular dynamics simulations. AB - We present an improved preconditioning scheme for electronic structure calculations based on the orbital transformation method. First, a preconditioner is developed which includes information from the full Kohn-Sham matrix but avoids computationally demanding diagonalisation steps in its construction. This reduces the computational cost of its construction, eliminating a bottleneck in large scale simulations, while maintaining rapid convergence. In addition, a modified form of Hotelling's iterative inversion is introduced to replace the exact inversion of the preconditioner matrix. This method is highly effective during molecular dynamics (MD), as the solution obtained in earlier MD steps is a suitable initial guess. Filtering small elements during sparse matrix multiplication leads to linear scaling inversion, while retaining robustness, already for relatively small systems. For system sizes ranging from a few hundred to a few thousand atoms, which are typical for many practical applications, the improvements to the algorithm lead to a 2-5 fold speedup per MD step. PMID- 26133421 TI - Adaptive resolution simulation of polarizable supramolecular coarse-grained water models. AB - Multiscale simulations methods, such as adaptive resolution scheme, are becoming increasingly popular due to their significant computational advantages with respect to conventional atomistic simulations. For these kind of simulations, it is essential to develop accurate multiscale water models that can be used to solvate biophysical systems of interest. Recently, a 4-to-1 mapping was used to couple the bundled-simple point charge water with the MARTINI model. Here, we extend the supramolecular mapping to coarse-grained models with explicit charges. In particular, the two tested models are the polarizable water and big multiple water models associated with the MARTINI force field. As corresponding coarse grained representations consist of several interaction sites, we couple orientational degrees of freedom of the atomistic and coarse-grained representations via a harmonic energy penalty term. This additional energy term aligns the dipole moments of both representations. We test this coupling by studying the system under applied static external electric field. We show that our approach leads to the correct reproduction of the relevant structural and dynamical properties. PMID- 26133422 TI - Accurate ab initio potential energy surface, thermochemistry, and dynamics of the F(-) + CH3F SN2 and proton-abstraction reactions. AB - We develop a full-dimensional global analytical potential energy surface (PES) for the F(-) + CH3F reaction by fitting about 50 000 energy points obtained by an explicitly correlated composite method based on the second-order Moller-Plesset perturbation-F12 and coupled-cluster singles, doubles, and perturbative triples F12a methods and the cc-pVnZ-F12 [n = D, T] basis sets. The PES accurately describes the (a) back-side attack Walden inversion mechanism involving the pre- and post-reaction (b) ion-dipole and (c) hydrogen-bonded complexes, the configuration-retaining (d) front-side attack and (e) double-inversion substitution pathways, as well as (f) the proton-abstraction channel. The benchmark quality relative energies of all the important stationary points are computed using the focal-point analysis (FPA) approach considering electron correlation up to coupled-cluster singles, doubles, triples, and perturbative quadruples method, extrapolation to the complete basis set limit, core-valence correlation, and scalar relativistic effects. The FPA classical(adiabatic) barrier heights of (a), (d), and (e) are -0.45(-0.61), 46.07(45.16), and 29.18(26.07) kcal mol(-1), respectively, the dissociation energies of (b) and (c) are 13.81(13.56) and 13.73(13.52) kcal mol(-1), respectively, and the endothermicity of (f) is 42.54(38.11) kcal mol(-1). Quasiclassical trajectory computations of cross sections, scattering (theta) and initial attack (alpha) angle distributions, as well as translational and internal energy distributions are performed for the F(-) + CH3F(v = 0) reaction using the new PES. Apart from low collision energies (Ecoll), the SN2 excitation function is nearly constant, the abstraction cross sections rapidly increase with Ecoll from a threshold of ~40 kcal mol(-1), and retention trajectories via double inversion are found above Ecoll = ~ 30 kcal mol(-1), and at Ecoll = ~ 50 kcal mol(-1), the front-side attack cross sections start to increase very rapidly. At low Ecoll, the indirect mechanism dominates (mainly isotropic backward-forward symmetric theta distribution and translationally cold products) and significant long-range orientation effects (isotropic alpha distribution) and barrier recrossings are found. At higher Ecoll, the SN2 reaction mainly proceeds with direct rebound mechanism (backward scattering and hot product translation). PMID- 26133423 TI - Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations. AB - In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n -> pi(*) transition induces a cleavage of the C-N single bond of 2 formyl-2H-azirine to yield beta-formylvinylnitrene in open-shell singlet state. However, the n -> pi(*) excitation of the imine chromophore results in a cleavage of the C-C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. beta-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed into 2-formyl-2H-azirine and oxazole, respectively. The N-O bond cleavages on both S1((1)pipi(*)) and S2((1)nNpi(*)) of isoxazole are ultrafast processes, and they give products of 2 formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet beta-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H azirines and isoxazoles. PMID- 26133424 TI - A model study of assisted adiabatic transfer of population in the presence of collisional dephasing. AB - Previous studies have demonstrated that when experimental conditions generate non adiabatic dynamics that prevents highly efficient population transfer between states of an isolated system by stimulated Raman adiabatic passage (STIRAP), the addition of an auxiliary counter-diabatic field (CDF) can restore most or all of that efficiency. This paper examines whether that strategy is also successful in a non-isolated system in which the energies of the states fluctuate, e.g., when a solute is subject to collisions with solvent. We study population transfer in two model systems: (i) the three-state system used by Demirplak and Rice [J. Chem. Phys. 116, 8028 (2002)] and (ii) a four-state system, derived from the simulation studies of Demirplak and Rice [J. Chem. Phys. 125, 194517 (2006)], that mimics HCl in liquid Ar. Simulation studies of the vibrational manifold of HCl in dense fluid Ar show that the collision induced vibrational energy level fluctuations have asymmetric distributions. Representations of these asymmetric energy level fluctuation distributions are used in both models (i) and (ii). We identify three sources of degradation of the efficiency of STIRAP generated selective population transfer in model (ii): too small pulse areas of the laser fields, unwanted interference arising from use of strong fields, and the vibrational detuning. For both models (i) and (ii), our examination of the efficiency of STIRAP + CDF population transfer under the influence of the asymmetric distribution of the vibrational energy fluctuations shows that there is a range of field strengths and pulse durations under which STIRAP + CDF control of population transfer has greater efficiency than does STIRAP generated population transfer. PMID- 26133425 TI - Fe2: As simple as a Herculean labour. Neutral (Fe2), cationic (Fe2(+)), and anionic (Fe2(-)) species. AB - We have studied 175 molecular states of the Fe2 diatomic by constructing full potential energy curves dissociating to the ground Fe((5)D) + Fe((5)D) and first excited Fe((5)D) + Fe((5)F) dissociation channels by multireference configuration interaction methods and large basis sets. The ground X(9)Sigmag (-) and the first excited (7)Sigmau (-) states have been detailed by a multitude of plain and explicitly correlated F12 methods at both the valence and core-valence computational levels. The potential curves of most of the states present strong interactions/avoided crossings that trigger a severe non adiabatic behavior. For reasons of completeness, the ground states of the charged Fe2 (-,+) species have also been considered. PMID- 26133426 TI - The temperature and size distribution of large water clusters from a non equilibrium model. AB - A hybrid Lagrangian-Eulerian approach is used to examine the properties of water clusters formed in neon-water vapor mixtures expanding through microscale conical nozzles. Experimental size distributions were reliably determined by the sodium doping technique in a molecular beam machine. The comparison of computed size distributions and experimental data shows satisfactory agreement, especially for (H2O)n clusters with n larger than 50. Thus validated simulations provide size selected cluster temperature profiles in and outside the nozzle. This information is used for an in-depth analysis of the crystallization and water cluster aggregation dynamics of recently reported supersonic jet expansion experiments. PMID- 26133427 TI - Accurate ab initio vibrational energies of methyl chloride. AB - Two new nine-dimensional potential energy surfaces (PESs) have been generated using high-level ab initio theory for the two main isotopologues of methyl chloride, CH3 (35)Cl and CH3 (37)Cl. The respective PESs, CBS-35( HL), and CBS 37( HL), are based on explicitly correlated coupled cluster calculations with extrapolation to the complete basis set (CBS) limit, and incorporate a range of higher-level (HL) additive energy corrections to account for core-valence electron correlation, higher-order coupled cluster terms, scalar relativistic effects, and diagonal Born-Oppenheimer corrections. Variational calculations of the vibrational energy levels were performed using the computer program TROVE, whose functionality has been extended to handle molecules of the form XY 3Z. Fully converged energies were obtained by means of a complete vibrational basis set extrapolation. The CBS-35( HL) and CBS-37( HL) PESs reproduce the fundamental term values with root-mean-square errors of 0.75 and 1.00 cm(-1), respectively. An analysis of the combined effect of the HL corrections and CBS extrapolation on the vibrational wavenumbers indicates that both are needed to compute accurate theoretical results for methyl chloride. We believe that it would be extremely challenging to go beyond the accuracy currently achieved for CH3Cl without empirical refinement of the respective PESs. PMID- 26133428 TI - Ab initio intermolecular potential energy surface and thermophysical properties of nitrous oxide. AB - We present an analytical intermolecular potential energy surface (PES) for two rigid nitrous oxide (N2O) molecules derived from high-level quantum-chemical ab initio calculations. Interaction energies for 2018 N2O-N2O configurations were computed utilizing the counterpoise-corrected supermolecular approach at the CCSD(T) level of theory using basis sets up to aug-cc-pVQZ supplemented with bond functions. A site-site potential function with seven sites per N2O molecule was fitted to the pair interaction energies. We validated our PES by computing the second virial coefficient as well as shear viscosity and thermal conductivity in the dilute-gas limit. The values of these properties are substantiated by the best experimental data. PMID- 26133429 TI - Chemical dynamics simulations of the monohydrated OH(-)(H2O) + CH3I reaction. Atomic-level mechanisms and comparison with experiment. AB - Direct dynamics simulations, with B97-1/ECP/d theory, were performed to study the role of microsolvation for the OH(-)(H2O) + CH3I reaction. The SN2 reaction dominates at all reactant collision energies, but at higher collision energies proton transfer to form CH2I(-), and to a lesser extent CH2I(-) (H2O), becomes important. The SN2 reaction occurs by direct rebound and stripping mechanisms, and 28 different indirect atomistic mechanisms, with the latter dominating. Important components of the indirect mechanisms are the roundabout and formation of SN2 and proton transfer pre-reaction complexes and intermediates, including [CH3--I--OH](-). In contrast, for the unsolvated OH(-) + CH3I SN2 reaction, there are only seven indirect atomistic mechanisms and the direct mechanisms dominate. Overall, the simulation results for the OH(-)(H2O) + CH3I SN2 reaction are in good agreement with experiment with respect to reaction rate constant, product branching ratio, etc. Differences between simulation and experiment are present for the SN2 velocity scattering angle at high collision energies and the proton transfer probability at low collision energies. Equilibrium solvation by the H2O molecule is unimportant. The SN2 reaction is dominated by events in which H2O leaves the reactive system as CH3OH is formed or before CH3OH formation. Formation of solvated products is unimportant and participation of the (H2O)CH3OH --I(-) post-reaction complex for the SN2 reaction is negligible. PMID- 26133430 TI - On the ultrafast charge migration and subsequent charge directed reactivity in Cl?N halogen-bonded clusters following vertical ionization. AB - In this article, we have presented ultrafast charge transfer dynamics through halogen bonds following vertical ionization of representative halogen bonded clusters. Subsequent hole directed reactivity of the radical cations of halogen bonded clusters is also discussed. Furthermore, we have examined effect of the halogen bond strength on the electron-electron correlation- and relaxation-driven charge migration in halogen bonded complexes. For this study, we have selected A Cl (A represents F, OH, CN, NH2, CF3, and COOH substituents) molecules paired with NH3 (referred as ACl:NH3 complex): these complexes exhibit halogen bonds. To the best of our knowledge, this is the first report on purely electron correlation- and relaxation-driven ultrafast (attosecond) charge migration dynamics through halogen bonds. Both density functional theory and complete active space self-consistent field theory with 6-31 + G(d, p) basis set are employed for this work. Upon vertical ionization of NCCl?NH3 complex, the hole is predicted to migrate from the NH3-end to the ClCN-end of the NCCl?NH3 complex in approximately 0.5 fs on the D0 cationic surface. This hole migration leads to structural rearrangement of the halogen bonded complex, yielding hydrogen bonding interaction stronger than the halogen bonding interaction on the same cationic surface. Other halogen bonded complexes, such as H2NCl:NH3, F3CCl:NH3, and HOOCCl:NH3, exhibit similar charge migration following vertical ionization. On the contrary, FCl:NH3 and HOCl:NH3 complexes do not exhibit any charge migration following vertical ionization to the D0 cation state, pointing to interesting halogen bond strength-dependent charge migration. PMID- 26133431 TI - The effect of Coulomb interactions on nonlinear thermovoltage and thermocurrent in quantum dots. AB - In the present work, we theoretically study the nonlinear regime of charge transport through a quantum dot coupled to the source and drain reservoirs. The investigation is carried out using a nonequilibrium Green's function formalism beyond the Hartree-Fock approximation. Employed approximations for the relevant Green's functions allow to trace a transition from Coulomb blockade regime to Kondo regime in the thermoelectric transport. Effects arising when electrons move in response to thermal gradient applied across the system are discussed, including experimentally observed thermovoltage zeros. PMID- 26133432 TI - Electronic spectra of linear HC5H and cumulene carbene H2C5. AB - The 1(3)Sigmau (-)<-X(3)Sigmag (-) transition of linear HC5H (A) has been observed in a neon matrix and gas phase. The assignment is based on mass selective experiments, extrapolation of previous results of the longer HC2n+1H homologues, and density functional and multi-state CASPT2 theoretical methods. Another band system starting at 303 nm in neon is assigned as the 1(1)A1<-X~(1)A1 transition of the cumulene carbene pentatetraenylidene H2C5 (B). PMID- 26133433 TI - State interactions and illumination of hidden states through perturbations and observations of new states: High energy resonance enhanced multiphoton ionization of HI. AB - Hydrogen iodide, a Hund's case (c) molecule, serves as a benchmark compound for studying rich molecular state interactions between Rydberg and valence states as well as between Rydberg states at high energies (72,300-74,600 cm(-1)) by mass resolved resonance enhanced multiphoton ionization (REMPI). Perturbations in the spectra appearing as deformations in line-positions, line-intensities, and linewidths are found to be either due to near-degenerate or non-degenerate interactions, both homogeneous and heterogeneous in nature. Perturbation analyses allow indirect observation as well as characterization of "hidden states" to some extent. Furthermore, new observable spectral features are assigned and characterized. PMID- 26133434 TI - Sub-Doppler infrared spectroscopy of propargyl radical (H2CCCH) in a slit supersonic expansion. AB - The acetylenic CH stretch mode (nu1) of propargyl (H2CCCH) radical has been studied at sub-Doppler resolution (~60 MHz) via infrared laser absorption spectroscopy in a supersonic slit-jet discharge expansion, where low rotational temperatures (Trot = 13.5(4) K) and lack of spectral congestion permit improved determination of band origin and rotational constants for the excited state. For the lowest J states primarily populated in the slit jet cooled expansion, fine structure due to the unpaired electron spin is resolved completely, which permits accurate analysis of electron spin-rotation interactions in the vibrationally excited states (epsilonaa = - 518.1(1.8), epsilonbb = - 13.0(3), epsiloncc = - 1.8(3) MHz). In addition, hyperfine broadening in substantial excess of the sub Doppler experimental linewidths is observed due to nuclear spin-electron spin contributions at the methylenic (-CH2) and acetylenic (-CH) positions, which permits detailed modeling of the fine/hyperfine structure line contours. The results are consistent with a delocalized radical spin density extending over both methylenic and acetylenic C atoms, in excellent agreement with simple resonance structures as well as ab initio theoretical calculations. PMID- 26133435 TI - Non-Newtonian behavior and molecular structure of Cooee bitumen under shear flow: A non-equilibrium molecular dynamics study. AB - The rheology and molecular structure of a model bitumen (Cooee bitumen) under shear are investigated in the non-Newtonian regime using non-equilibrium molecular dynamics simulations. The shear viscosity, normal stress differences, and pressure of the bitumen mixture are computed at different shear rates and different temperatures. The model bitumen is shown to be a shear-thinning fluid at all temperatures. In addition, the Cooee model is able to reproduce experimental results showing the formation of nanoaggregates composed of stacks of flat aromatic molecules in bitumen. These nanoaggregates are immersed in a solvent of saturated hydrocarbon molecules. At a fixed temperature, the shear shinning behavior is related not only to the inter- and intramolecular alignments of the solvent molecules but also to the decrease of the average size of the nanoaggregates at high shear rates. The variation of the viscosity with temperature at different shear rates is also related to the size and relative composition of the nanoaggregates. The slight anisotropy of the whole sample due to the nanoaggregates is considered and quantified. Finally, the position of bitumen mixtures in the broad literature of complex systems such as colloidal suspensions, polymer solutions, and associating polymer networks is discussed. PMID- 26133436 TI - Nonlinear dielectric response of polar liquids. AB - The dielectric constant of a polar liquid in a strong electric field changes, in the lowest order, proportionally to the squared field magnitude. The proportionality coefficient (dielectric slope) is traditionally analyzed by mean field models in terms of the saturation of alignment of individual dipoles as prescribed by the Langevin function. Only a decrease of the dielectric constant induced by the field is allowed by this model, in contrast to observations. Here, the dielectric slope is expressed in terms of the fourth-order cumulant of the liquid dipole moment. The cumulant is in turn separated into the two-particle dipolar correlations, expressed in terms of the Kirkwood factor and the liquid compressibility, and higher, triple and four-particle, dipolar correlations. The model allows both positive and negative dielectric slopes. Two-particle and higher-order correlations largely compensate each other. The analysis of experimental data suggests that dielectric slope gives experimental access to non trivial triple and four-particle orientational correlations in polar liquids. PMID- 26133437 TI - Clathrate structure-type recognition: Application to hydrate nucleation and crystallisation. AB - For clathrate-hydrate polymorphic structure-type (sI versus sII), geometric recognition criteria have been developed and validated. These are applied to the study of the rich interplay and development of both sI and sII motifs in a variety of hydrate-nucleation events for methane and H2S hydrate studied by direct and enhanced-sampling molecular dynamics (MD) simulations. In the case of nucleation of methane hydrate from enhanced-sampling simulation, we notice that already at the transition state, ~80% of the enclathrated CH4 molecules are contained in a well-structured (sII) clathrate-like crystallite. For direct MD simulation of nucleation of H2S hydrate, some sI/sII polymorphic diversity was encountered, and it was found that a realistic dissipation of the nucleation energy (in view of non-equilibrium relaxation to either microcanonical (NVE) or isothermal-isobaric (NPT) distributions) is important to determine the relative propensity to form sI versus sII motifs. PMID- 26133438 TI - Possible existence of two amorphous phases of D-mannitol related by a first-order transition. AB - We report that the common polyalcohol D-mannitol may have two amorphous phases related by a first-order transition. Slightly above its glass transition temperature Tg (284 K), the supercooled liquid (SCL) of D-mannitol transforms to a low-energy, apparently amorphous phase with stronger hydrogen bonds. The enthalpy of this so-called Phase X is approximately halfway between those of the known amorphous and crystalline phases, a position low for glass aging and high for crystal polymorphs. Similar to the SCL, Phase X is transparent with broad X ray diffraction and Raman scattering; upon temperature cycling, it exhibits a glass-transition-like change of heat capacity. On fast heating, Phase X transforms back to the SCL near Tg + 50 K, enabling a determination of their equilibrium temperature. The presence of D-sorbitol as a plasticizer enables observation of a first-order transition from the SCL to Phase X entirely in the liquid state (liquid-liquid transition). The transition from D-mannitol's SCL to Phase X has intriguing similarities with the formation of the glacial phase of triphenyl phosphite (TPP) and the conversion from high-density to low-density amorphous ice, both studied intensely in the context of polyamorphism. All three processes occur near Tg with substantial enthalpy decrease toward the crystalline phases; the processes in water and D-mannitol both strengthen the hydrogen bonds. In contrast to TPP, D-mannitol's Phase X forms more rapidly and can transform back to the SCL. These features make D-mannitol a valuable new model for understanding polyamorphism. PMID- 26133439 TI - Investigation of the CH3Cl + CN(-) reaction in water: Multilevel quantum mechanics/molecular mechanics study. AB - The CH3Cl + CN(-) reaction in water was studied using a multilevel quantum mechanics/molecular mechanics (MM) method with the multilevels, electrostatic potential, density functional theory (DFT) and coupled-cluster single double triple (CCSD(T)), for the solute region. The detailed, back-side attack SN2 reaction mechanism was mapped along the reaction pathway. The potentials of mean force were calculated under both the DFT and CCSD(T) levels for the reaction region. The CCSD(T)/MM level of theory presents a free energy activation barrier height at 20.3 kcal/mol, which agrees very well with the experiment value at 21.6 kcal/mol. The results show that the aqueous solution has a dominant role in shaping the potential of mean force. The solvation effect and the polarization effect together increase the activation barrier height by ~11.4 kcal/mol: the solvation effect plays a major role by providing about 75% of the contribution, while polarization effect only contributes 25% to the activation barrier height. Our calculated potential of mean force under the CCSD(T)/MM also has a good agreement with the one estimated using data from previous gas-phase studies. PMID- 26133440 TI - Dynamic heterogeneity in crossover spin facilitated model of supercooled liquid and fractional Stokes-Einstein relation. AB - Kinetically constrained models have gained much interest as models that assign the origins of interesting dynamic properties of supercooled liquids to dynamical facilitation mechanisms that have been revealed in many experiments and numerical simulations. In this work, we investigate the dynamic heterogeneity in the fragile-to-strong liquid via Monte Carlo method using the model that linearly interpolates between the strong liquid-like behavior and the fragile liquid-like behavior by an asymmetry parameter b. When the asymmetry parameter is sufficiently small, smooth fragile-to-strong transition is observed both in the relaxation time and the diffusion constant. Using these physical quantities, we investigate fractional Stokes-Einstein relations observed in this model. When b is fixed, the system shows constant power law exponent under the temperature change, and the exponent has the value between that of the Frederickson-Andersen model and the East model. Furthermore, we investigate the dynamic length scale of our systems and also find the crossover relation between the relaxation time. We ascribe the competition between energetically favored symmetric relaxation mechanism and entropically favored asymmetric relaxation mechanism to the fragile to-strong crossover behavior. PMID- 26133441 TI - The interplay between dynamic heterogeneities and structure of bulk liquid water: A molecular dynamics simulation study. AB - In order to study the interplay between dynamical heterogeneities and structural properties of bulk liquid water in the temperature range 130-350 K, thus including the supercooled regime, we use the explicit trend of the distribution functions of some molecular properties, namely, the rotational relaxation constants, the atomic mean-square displacements, the relaxation of the cross correlation functions between the linear and squared displacements of H and O atoms of each molecule, the tetrahedral order parameter q and, finally, the number of nearest neighbors (NNs) and of hydrogen bonds (HBs) per molecule. Two different potentials are considered: TIP4P-Ew and a model developed in this laboratory for the study of nanoconfined water. The results are similar for the dynamical properties, but are markedly different for the structural characteristics. In particular, for temperatures higher than that of the dynamic crossover between "fragile" (at higher temperatures) and "strong" (at lower temperatures) liquid behaviors detected around 207 K, the rotational relaxation of supercooled water appears to be remarkably homogeneous. However, the structural parameters (number of NNs and of HBs, as well as q) do not show homogeneous distributions, and these distributions are different for the two water models. Another dynamic crossover between "fragile" (at lower temperatures) and "strong" (at higher temperatures) liquid behaviors, corresponding to the one found experimentally at T(*) ~ 315 +/- 5 K, was spotted at T(*) ~ 283 K and T(*) ~ 276 K for the TIP4P-Ew and the model developed in this laboratory, respectively. It was detected from the trend of Arrhenius plots of dynamic quantities and from the onset of a further heterogeneity in the rotational relaxation. To our best knowledge, it is the first time that this dynamical crossover is detected in computer simulations of bulk water. On the basis of the simulation results, the possible mechanisms of the two crossovers at molecular level are discussed. PMID- 26133442 TI - Cooling-rate dependence of kinetic and mechanical stabilities of simulated glasses. AB - Glasses created through vapor deposition on a substrate maintained at a proper temperature possess higher kinetic and mechanical stabilities than glasses created by cooling at a constant rate. Molecular dynamics simulations are being increasingly used to understand why vapor deposition improves glasses' stability. There are, however, few detailed molecular dynamics studies of the dependence of the properties of glasses cooled at a constant rate on the rate of cooling. Thus, there is no clear benchmark for comparing ultrastable simulated glasses to simulated glasses prepared through cooling at a constant rate. Here, we examine the dependence of the properties of simulated glasses on the cooling rate used in their preparation. We examine the kinetic stability by measuring the time it takes for a glass to transform back to a liquid upon heating and heterogeneous dynamics during heating. We also examine properties of the energy landscape, and we evaluate mechanical stability by calculating the shear modulus of the glass. The methods outlined here can be used to assess kinetic and mechanical stabilities of simulated glasses generated using specialized algorithms and provide a benchmark for those algorithms. PMID- 26133443 TI - Pressure-induced reversible phase transition in thiourea dioxide crystal. AB - The effect of high pressure on the crystal structure of thiourea dioxide has been investigated by Raman spectroscopy and angle-dispersive X-ray diffraction (ADXRD) in a diamond anvil cell up to 10.3 GPa. The marked changes in the Raman spectra at 3.7 GPa strongly indicated a structural phase transition associated with the distortions of hydrogen bonding. There were no further changes up to the maximum pressure of 10.3 GPa and the observed transition was completely reversible when the system was brought back to ambient pressure. This transition was further confirmed by the changes of ADXRD spectra. The high-pressure phase was indexed and refined to an orthorhombic structure with a possible space group Pbam. The results from the first-principles calculations suggested that this phase transition was mainly related to the changes of hydrogen-bonded networks in thiourea dioxide. PMID- 26133444 TI - Geometric and electronic structures of potassium-adsorbed rubrene complexes. AB - The geometric and electronic structures of potassium-adsorbed rubrene complexes are studied in this article. It is found that the potassium-rubrene (K1RUB) complexes inherit the main symmetry characteristics from their pristine counterparts and are thus classified into D2- and C2h-like complexes according to the relative orientations of the four phenyl side groups. The geometric structures of K1RUB are governed by two general effects on the total energy: Deformation of the carbon frame of the pristine rubrene increases the total energy, while proximity of the potassium ion to the phenyl ligands decreases the energy. Under these general rules, the structures of D2- and C2h-like K1RUB, however, exhibit their respective peculiarities. These peculiarities can be illustrated by their energy profiles of equilibrium structures. For the potassium adsorption-sites, the D2-like complexes show minimum-energy basins, whereas the C2h-like ones have single-point minimum-energies. If the potassium atom ever has the energy to diffuse from the minimum-energy site, the potassium diffusion path on the D2-like complexes is most likely along the backbone in contrast to the C2h like ones. Although the electronic structures of the minimum-energy structures of D2- and C2h-like K1RUB are very alike, decompositions of their total spectra reveal insights into the electronic structures. First, the spectral shapes are mainly determined by the facts that, in comparison with the backbone carbons, the phenyl carbons have more uniform chemical environments and far less contributions to the electronic structures around the valence-band edge. Second, the electron dissociated from the potassium atom mainly remains on the backbone and has little effects on the electronic structures of the phenyl groups. Third, the two phenyls on the same side of the backbone as the potassium atom have more similar chemical environments than the other two on the opposite side, which leads to the largely enhanced resemblance of the simulated to the experimental spectra. Fourth, the HOMO and LUMO are mainly the alpha and beta components of the 2p orbitals of the backbone carbons, respectively. PMID- 26133445 TI - Tuning interfacial thermal conductance of graphene embedded in soft materials by vacancy defects. AB - Nanocomposites based on graphene dispersed in matrices of soft materials are promising thermal management materials. Their effective thermal conductivity depends on both the thermal conductivity of graphene and the conductance of the thermal transport across graphene-matrix interfaces. Here, we report on molecular dynamics simulations of the thermal transport across the interfaces between defected graphene and soft materials in two different modes: in the "across" mode, heat enters graphene from one side of its basal plane and leaves through the other side; in the "non-across" mode, heat enters or leaves graphene simultaneously from both sides of its basal plane. We show that as the density of vacancy defects in graphene increases from 0% to 8%, the conductance of the interfacial thermal transport in the "across" mode increases from 160.4 +/- 16 to 207.8 +/- 11 MW/m(2) K, while that in the "non-across" mode increases from 7.2 +/ 0.1 to 17.8 +/- 0.6 MW/m(2) K. The molecular mechanisms for these variations of thermal conductance are clarified using the phonon density of states and structural characteristics of defected graphene. On the basis of these results and effective medium theory, we show that it is possible to enhance the effective thermal conductivity of thermal nanocomposites by tuning the density of vacancy defects in graphene despite the fact that graphene's thermal conductivity always decreases as vacancy defects are introduced. PMID- 26133446 TI - Stability of micro-Cassie states on rough substrates. AB - We numerically study different forms of nanoscale gaseous domains on a model for rough surfaces. Our calculations based on the constrained lattice density functional theory show that the inter-connectivity of pores surrounded by neighboring nanoposts, which model the surface roughness, leads to the formation of stable microscopic Cassie states. We investigate the dependence of the stability of the micro-Cassie states on substrate roughness, fluid-solid interaction, and chemical potential and then address the differences between the origin of the micro-Cassie states and that of surface nanobubbles within similar models. Finally, we show that the micro-Cassie states share some features with experimentally observed micropancakes at solid-water interfaces. PMID- 26133447 TI - Selective encapsulation by Janus particles. AB - We employ Monte Carlo simulation to examine encapsulation in a system comprising Janus oblate spheroids and isotropic spheres. More specifically, the impact of variations in temperature, particle size, inter-particle interaction range, and strength is examined for a system in which the spheroids act as the encapsulating agents and the spheres as the encapsulated guests. In this picture, particle interactions are described by a quasi-square-well patch model. This study highlights the environmental adaptation and selectivity of the encapsulation system to changes in temperature and guest particle size, respectively. Moreover, we identify an important range in parameter space where encapsulation is favored, as summarized by an encapsulation map. Finally, we discuss the generalization of our results to systems having a wide range of particle geometries. PMID- 26133448 TI - Ten new predicted covalent organic frameworks with strong optical response in the visible and near infrared. AB - We use density functional theory to predict and evaluate 10 novel covalent organic frameworks (COFs), labeled (X4Y)(BDC)3, (X = C/Si; Y = C, Si, Ge, Sn, and Pb), with topology based on metal organic framework isoreticular metal-organic framework (IRMOF-1), but with new elements substituted for the corner atoms. We show that these new materials are stable structures using frequency calculations. For two structures, (C4C and Si4C) molecular dynamics simulations were performed to demonstrate stability of the systems up to 600 K for 10 ps. This demonstrates the remarkable stability of these systems, some of which may be experimentally accessible. For the C4C material, we also explored the stability of isolated corners and linkers and vacuum and started to build the structure from these pieces. We discuss the equilibrium lattice parameters, formation enthalpies, electronic structures, chemical bonding, and mechanical and optical properties. The predicted bulk moduli of these COFs range from 18.9 to 23.9 GPa, larger than that of IRMOF-1 (ca. 15.4 GPa), and larger than many existing 3D COF materials. The band gaps range from 1.5 to 2.1 eV, corresponding to 600-830 nm wavelength (orange through near infrared). The negative values of the formation enthalpy suggest that they are stable and should be experimentally accessible under suitable conditions. Seven materials distort the crystal structure to a lower space group symmetry Fm-3, while three materials maintain the original Fm-3m space group symmetry. All of the new materials are highly luminescent. We hope that this work will inspire efforts for experimental synthesis of these new materials. PMID- 26133449 TI - Structure, thermodynamic properties, and phase diagrams of few colloids confined in a spherical pore. AB - We study a system of few colloids confined in a small spherical cavity with event driven molecular dynamics simulations in the canonical ensemble. The colloidal particles interact through a short range square-well potential that takes into account the basic elements of attraction and excluded-volume repulsion of the interaction among colloids. We analyze the structural and thermodynamic properties of this few-body confined system in the framework of inhomogeneous fluids theory. Pair correlation function and density profile are used to determine the structure and the spatial characteristics of the system. Pressure on the walls, internal energy, and surface quantities such as surface tension and adsorption are also analyzed for a wide range of densities and temperatures. We have characterized systems from 2 to 6 confined particles, identifying distinctive qualitative behavior over the thermodynamic plane T - rho, in a few particle equivalent to phase diagrams of macroscopic systems. Applying the extended law of corresponding states, the square well interaction is mapped to the Asakura-Oosawa model for colloid-polymer mixtures. We link explicitly the temperature of the confined square-well fluid to the equivalent packing fraction of polymers in the Asakura-Oosawa model. Using this approach, we study the confined system of few colloids in a colloid-polymer mixture. PMID- 26133450 TI - Thermoelectric energy recovery at ionic-liquid/electrode interface. AB - A thermally chargeable capacitor containing a binary solution of 1-ethyl-3 methylimidazolium bis(trifluoromethylsulfonyl)-imide in acetonitrile is electrically charged by applying a temperature gradient to two ideally polarisable electrodes. The corresponding thermoelectric coefficient is -1.7 mV/K for platinum foil electrodes and -0.3 mV/K for nanoporous carbon electrodes. Stored electrical energy is extracted by discharging the capacitor through a resistor. The measured capacitance of the electrode/ionic-liquid interface is 5 MUF for each platinum electrode while it becomes four orders of magnitude larger, ~36 mF, for a single nanoporous carbon electrode. Reproducibility of the effect through repeated charging-discharging cycles under a steady-state temperature gradient demonstrates the robustness of the electrical charging process at the liquid/electrode interface. The acceleration of the charging by convective flows is also observed. This offers the possibility to convert waste-heat into electric energy without exchanging electrons between ions and electrodes, in contrast to what occurs in most thermogalvanic cells. PMID- 26133451 TI - Self-crowding induced phase separation in protein dispersions. AB - The coupling between protein conformation, molecular volume, and solution phase behaviour is studied theoretically for a two-state, coarse-grained protein model in which protein molecules can reversibly switch between a native and a non native excited state. In the model, native and non-native conformers are represented by perfect spheres with different hard-core diameters. We presume the larger, non-native species to attract each other through some unspecified potential. We find that at low concentrations the native state is stabilised energetically and that at high concentrations the native state is again stabilised but this time by self-crowding, i.e., a lack of free volume. These two regimes are separated by two first-order transitions from a region where the non native conformational state is prevalent, stabilised by attractive interactions between the proteins. The calculated phase diagram is very sensitive to even quite small differences in particle volumes and has unusual features, including the loss of a critical point if the size difference is sufficiently large. PMID- 26133452 TI - Fluids confined in wedges and by edges: From cluster integrals to thermodynamic properties referred to different regions. AB - Recently, new insights into the relation between the geometry of the vessel that confines a fluid and its thermodynamic properties were traced through the study of cluster integrals for inhomogeneous fluids. In this work, I analyze the thermodynamic properties of fluids confined in wedges or by edges, emphasizing on the question of the region to which these properties refer. In this context, the relations between the line-thermodynamic properties referred to different regions are derived as analytic functions of the dihedral angle alpha, for 0 < alpha < 2pi, which enables a unified approach to both edges and wedges. As a simple application of these results, I analyze the properties of the confined gas in the low-density regime. Finally, using recent analytic results for the second cluster integral of the confined hard sphere fluid, the low density behavior of the line thermodynamic properties is analytically studied up to order two in the density for 0 < alpha < 2pi and by adopting different reference regions. PMID- 26133453 TI - An analytical equation of state for describing isotropic-nematic phase equilibria of Lennard-Jones chain fluids with variable degree of molecular flexibility. AB - We develop an equation of state (EoS) for describing isotropic-nematic (IN) phase equilibria of Lennard-Jones (LJ) chain fluids. The EoS is developed by applying a second order Barker-Henderson perturbation theory to a reference fluid of hard chain molecules. The chain molecules consist of tangentially bonded spherical segments and are allowed to be fully flexible, partially flexible (rod-coil), or rigid linear. The hard-chain reference contribution to the EoS is obtained from a Vega-Lago rescaled Onsager theory. For the description of the (attractive) dispersion interactions between molecules, we adopt a segment-segment approach. We show that the perturbation contribution for describing these interactions can be divided into an "isotropic" part, which depends only implicitly on orientational ordering of molecules (through density), and an "anisotropic" part, for which an explicit dependence on orientational ordering is included (through an expansion in the nematic order parameter). The perturbation theory is used to study the effect of chain length, molecular flexibility, and attractive interactions on IN phase equilibria of pure LJ chain fluids. Theoretical results for the IN phase equilibrium of rigid linear LJ 10-mers are compared to results obtained from Monte Carlo simulations in the isobaric-isothermal (NPT) ensemble, and an expanded formulation of the Gibbs-ensemble. Our results show that the anisotropic contribution to the dispersion attractions is irrelevant for LJ chain fluids. Using the isotropic (density-dependent) contribution only (i.e., using a zeroth order expansion of the attractive Helmholtz energy contribution in the nematic order parameter), excellent agreement between theory and simulations is observed. These results suggest that an EoS contribution for describing the attractive part of the dispersion interactions in real LCs can be obtained from conventional theoretical approaches designed for isotropic fluids, such as a Perturbed-Chain Statistical Associating Fluid Theory approach. PMID- 26133454 TI - Operational electrochemical stability of thiophene-thiazole copolymers probed by resonant Raman spectroscopy. AB - We report on the electrochemical stability of hole polarons in three conjugated polymers probed by resonant Raman spectroscopy. The materials considered are all isostructural to poly(3-hexyl)thiophene, where thiazole units have been included to systematically deepen the energy level of the highest occupied molecular orbital (HOMO). We demonstrate that increasing the thiazole content planarizes the main conjugated backbone of the polymer and improves the electrochemical stability in the ground state. However, these more planar thiazole containing polymers are increasingly susceptible to electrochemical degradation in the polaronic excited state. We identify the degradation mechanism, which targets the C=N bond in the thiazole units and results in disruption of the main polymer backbone conjugation. The introduction of thiazole units to deepen the HOMO energy level and increase the conjugated backbone planarity can be beneficial for the performance of certain optoelectronic devices, but the reduced electrochemical stability of the hole polaron may compromise their operational stability. PMID- 26133455 TI - Phase field modelling of strain induced crystal growth in an elastic matrix. AB - When a crystal phase grows in an amorphous matrix, such as a crystallisable elastomer, containing cross-links and/or entanglements, these "topological constraints" need to be pushed away from the crystal phase to allow further crystallization. The accumulation of these topological constraints in the vicinity of the crystal interface may store elastic energy and affect the phase transition. To evaluate the consequences of such mechanism, we introduce a phase field model based on the Flory theory of entropic elasticity. We show that the growth process is indeed sensibly affected, in particular, an exponential increase of the surface energy with the displacement of the interface is induced. This explains the formation of stable nano-crystallites as it is observed in the Strain Induced Crystallization (SIC) of natural rubber. Although simple, the model developed here is able to account for many interesting features of SIC, for instance, the crystallite shapes and their sizes which depend on the applied deformation. PMID- 26133456 TI - On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein. AB - The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data. PMID- 26133457 TI - A catalytic oligomeric motor that walks along a filament track. AB - Most biological motors in the cell execute chemically powered conformational changes as they walk on biopolymer filaments in order to carry out directed transport functions. Synthetic motors that operate in a similar manner are being studied since they have the potential to perform similar tasks in a variety of applications. In this paper, a synthetic nanomotor that moves along a filament track, without invoking motor conformational changes, is constructed and its properties are studied in detail. The motor is an oligomer comprising three linked beads with specific binding properties. The filament track is a stiff polymer chain, also described by a linear chain of linked coarse-grained molecular groups modeled as beads. Reactions on the filament that are catalyzed by a motor bead and use fuel in the environment, in conjunction within the binding affinities of the motor beads to the filament beads, lead to directed motion. The system operates out of equilibrium due to the state of the filament and supply of fuel. The motor, filament, and surrounding medium are all described at microscopic level that permits a full analysis of the motor motion. A stochastic model that captures the main trends seen in the simulations is also presented. The results of this study point to some of the key features that could be used to construct nanomotors that undergo biased walks powered by chemical reactions on filaments. PMID- 26133458 TI - Publisher's Note: "Impact of secondary structure and hydration water on the dielectric spectrum of poly-alanine and possible relation to the debate on slaved versus slaving water" [J. Chem. Phys. 142, 215104 (2015)]. PMID- 26133459 TI - Erratum: "Interfaces of propylene carbonate" [J. Chem. Phys. 138, 114708 (2013)]. PMID- 26133460 TI - Beneficial reciprocal effects of bone marrow stromal cells and Schwann cells from adult rats in a dynamic co-culture system in vitro without intercellular contact. AB - In order to examine how implanted bone marrow stromal cells (BMSCs) encourage peripheral nerve regeneration, the present study investigated the interaction of BMSCs and Schwann cells (SCs) using an indirect in vitro co-culture model. SCs and BMSCs were obtained from adult Sprague-Dawley rats. The passaged BMSCs were CD29- and CD44-positive but CD45-negative and were co-cultured with the primary SCs using a Millicell system, which allows BMSCs and SCs to grow in the same culture medium but without direct contact. Expression of the typical SC markers S 100 and glial fibrillary acidic protein (GFAP) of the treated BMSCs as well as the proliferation capacity of the co-cultured SCs was evaluated by immunocytochemical staining on the 3rd and 5th day of co-culture. Immunocytochemical staining showed that >75% of the BMSCs in the indirect co culture model were GFAP- and S-100-positive on the 3rd and 5th day after co culture, as opposed to <5% of the BMSCs in the control group. On the 3rd day after co-culture, only a few co-cultured BMSCs showed the typical SC-like morphology, while most BMSCs still kept their native appearance. By contrast, on the 5th day after co-culture, almost all of the co-cultured BMSCs appeared with the typical SC-like morphology. Furthermore, 70.71% of the SCs in the indirect co culture model were S-100-positive on the 5th day of co-culture, as opposed to >30.43% of the SCs in the control group. These results indicated that BMSCs may interact synergistically with SCs with regard to promoting peripheral nerve regeneration. PMID- 26133461 TI - Functional Imaging Biomarkers: Potential to Guide an Individualised Approach to Radiotherapy. AB - The identification of robust prognostic and predictive biomarkers would transform the ability to implement an individualised approach to radiotherapy. In this regard, there has been a surge of interest in the use of functional imaging to assess key underlying biological processes within tumours and their response to therapy. Importantly, functional imaging biomarkers hold the potential to evaluate tumour heterogeneity/biology both spatially and temporally. An ever increasing range of functional imaging techniques is now available primarily involving positron emission tomography and magnetic resonance imaging. Small scale studies across multiple tumour types have consistently been able to correlate changes in functional imaging parameters during radiotherapy with disease outcomes. Considerable challenges remain before the implementation of functional imaging biomarkers into routine clinical practice, including the inherent temporal variability of biological processes within tumours, reproducibility of imaging, determination of optimal imaging technique/combinations, timing during treatment and design of appropriate validation studies. PMID- 26133462 TI - Cardiac Side-effects From Breast Cancer Radiotherapy. AB - Breast cancer radiotherapy reduces the risk of cancer recurrence and death. However, it usually involves some radiation exposure of the heart and analyses of randomised trials have shown that it can increase the risk of heart disease. Estimates of the absolute risks of radiation-related heart disease are needed to help oncologists plan each individual woman's treatment. The risk for an individual woman varies according to her estimated cardiac radiation dose and her background risk of ischaemic heart disease in the absence of radiotherapy. When it is known, this risk can then be compared with the absolute benefit of the radiotherapy. At present, many UK cancer centres are already giving radiotherapy with mean heart doses of less than 3 Gy and for most women the benefits of the radiotherapy will probably far outweigh the risks. Technical approaches to minimising heart dose in breast cancer radiotherapy include optimisation of beam angles, use of multileaf collimator shielding, intensity-modulated radiotherapy, treatment in a prone position, treatment in deep inspiration (including the use of breath-hold and gating techniques), proton therapy and partial breast irradiation. The multileaf collimator is suitable for many women with upper pole left breast cancers, but for women with central or lower pole cancers, breath holding techniques are now recommended in national UK guidelines. Ongoing work aims to identify ways of irradiating pan-regional lymph nodes that are effective, involve minimal exposure of organs at risk and are feasible to plan, deliver and verify. These will probably include wide tangent-based field-in-field intensity modulated radiotherapy or arc radiotherapy techniques in combination with deep inspiratory breath-hold, and proton beam irradiation for women who have a high predicted heart dose from intensity-modulated radiotherapy. PMID- 26133463 TI - Exosome-based strategies for Diagnosis and Therapy. AB - Exosomes are small extracellular vesicles (30-120 nm) of endosomal origin, which are gaining the attention of the scientific community. Originally considered only a waste disposal system, they are now emerging as another class of signal mediators. Exosomes are secreted by any cell type and retrieved in every body fluid, such as blood, urine, saliva and amniotic liquid. Remarkably, their biochemical content includes not only lipids and proteins, but also nucleic acids, mainly miRNA and mRNA, with a few reports also indicating the presence of genomic and mitochondrial DNA. Their properties have stimulated extensive research to exploit them as a source of biomarkers for the diagnosis and the follow-up of several pathologies. Furthermore, exosomes are relatively robust and stable, so they appear attractive as gene and drug delivery vehicles. They have also revealed immunomodulatory and regenerative properties, which are encouraging their application for therapeutic purposes. Several issues remain to be addressed: exosome isolation is still time consuming and unsatisfactorily reproducible, making it difficult to compare results among laboratories, improve our knowledge of their physiological function and correlate their features with pathological outcomes. Nevertheless, the number of patents trying to address these problems is growing exponentially and many novelties will reach the scientific community in the next few years. PMID- 26133465 TI - Toxicity of environmental Gesagard to goldfish may be connected with induction of low intensity oxidative stress in concentration- and tissue-related manners. AB - Prometryn is a selective herbicide commonly used in agriculture as the commercial preparation, Gesagard. Goldfish (Carassius auratus) exposure for 96h to 0.2, 1, or 5mgL(-1) Gesagard 500FW (corresponding to 0.1, 0.5, and 2.5mgL(-1) of prometryn) on indices of oxidative stress (lipid peroxides, protein carbonyls, and thiol content) and activities of antioxidant and related enzymes in gills, liver, and kidney was studied. Gills appeared to be the most resistant to Gesagard treatment, reacting to only the highest concentration of herbicide with enhanced levels of low molecular mass thiols and activities of glutathione S transferase (GST) and glutathione reductase. Goldfish exposure to 0.2-5mgL(-1) Gesagard resulted in enhancement of carbonyl protein level and activity of superoxide dismutase (SOD), but reduced the lipid peroxide (LOOH) content and activity of glutathione peroxidase in liver. Kidney appeared to be the main target organ of Gesagard toxicity, showing the greatest number of parameters affected even under low concentrations of herbicide. An increase in the content of L-SH and activity of SOD was accompanied with decreased activities of catalase, GST, and glucose-6-phosphate dehydrogenase and reduced levels of LOOH in kidney of Gesagard treated fish. The treatment also induced various histological changes in goldfish liver and kidney which could be related to their dysfunction. The present study indicates that Gesagard induced oxidative stress of differing intensities in the three goldfish tissues and demonstrated that kidney would be the best target organ to analyze, reveal, and monitor Gesagard effects on fish. PMID- 26133466 TI - Identification of urine protein biomarkers with the potential for early detection of lung cancer. AB - Lung cancer is the leading cause of cancer-related deaths and has an overall 5 year survival rate lower than 15%. Large-scale clinical trials have demonstrated a significant relative reduction in mortality in high-risk individuals with low dose computed tomography screening. However, biomarkers capable of identifying the most at-risk population and detecting lung cancer before it becomes clinically apparent are urgently needed in the clinic. Here, we report the identification of urine biomarkers capable of detecting lung cancer. Using the well-characterized inducible Kras (G12D) mouse model of lung cancer, we identified alterations in the urine proteome in tumor-bearing mice compared with sibling controls. Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls. Importantly, we identified 7 proteins commonly found to be significantly up regulated in both tumor-bearing mice and patients. In an independent cohort, we showed that 2 of the 7 proteins were up-regulated in urine samples from lung cancer patients but not in those from controls. The kinetics of these proteins correlated with the disease state in the mouse model. These tumor biomarkers could potentially aid in the early detection of lung cancer. PMID- 26133468 TI - Radiographic Implications of Fat Grafting to the Reconstructed Breast. AB - Autologous fat transfer is often used to smooth contour irregularities in the reconstructed breast. A potential concern with this technique is that it results in calcified lesions in the breast that can complicate subsequent cancer surveillance. The purpose of this review was to determine how fat grafting to the reconstructed breast impacts postoperative breast imaging. This is a matched cohort analysis of patients who underwent postmastectomy breast reconstruction with and without fat grafting as a secondary procedure. Nonfat grafted reconstructive patients were matched based on age, year of initial reconstruction, and type of reconstruction. Postoperative imaging at our institution was required for inclusion. The two groups were compared in terms of incidence and distribution of radiographic studies performed in follow-up and the need for biopsies. Fifty-one reconstructed breasts with a history of fat grafting were compared to 51 nonfat grafted, reconstructed breasts. The fat grafted group underwent a total of 204 breast imaging studies over a mean follow-up of 4.2 years, while the nonfat grafted group underwent 167 studies over 4.1 years (p = 0.21). More mammograms, ultrasounds, and magnetic resonance images were performed after fat grafting, but a significant difference was evident only for mammography (34 versus 12, p = 0.05). The incidence of breast biopsy to clarify abnormal imaging was nonsignificantly higher in the fat grafted group (17.6% versus 7.8%, p = 0.14). Fewer than 10 percent of imaging studies in the fat grafted cohort were performed to investigate a clinical or radiographic abnormality occupying the same breast quadrant as prior fat injection. Breast cancer patients treated with fat grafting required more breast imaging and biopsies than their nonfat grafted counterparts, but the areas of suspicion poorly corresponded to the site of prior fat grafting. Multimodal breast reconstruction may drive the additional diagnostic burden and not the fat grafting technique itself. PMID- 26133469 TI - Palladium-platinum core-shell icosahedra with substantially enhanced activity and durability towards oxygen reduction. AB - Conformal deposition of platinum as ultrathin shells on facet-controlled palladium nanocrystals offers a great opportunity to enhance the catalytic performance while reducing its loading. Here we report such a system based on palladium icosahedra. Owing to lateral confinement imposed by twin boundaries and thus vertical relaxation only, the platinum overlayers evolve into a corrugated structure under compressive strain. For the core-shell nanocrystals with an average of 2.7 platinum overlayers, their specific and platinum mass activities towards oxygen reduction are enhanced by eight- and sevenfold, respectively, relative to a commercial catalyst. Density functional theory calculations indicate that the enhancement can be attributed to the weakened binding of hydroxyl to the compressed platinum surface supported on palladium. After 10,000 testing cycles, the mass activity of the core-shell nanocrystals is still four times higher than the commercial catalyst. These results demonstrate an effective approach to the development of electrocatalysts with greatly enhanced activity and durability. PMID- 26133470 TI - Associating cooking additives with sodium hydroxide to pretreat bamboo residues for improving the enzymatic saccharification and monosaccharides production. AB - Cooking additive pulping technique is used in kraft mill to increase delignification degree and pulp yield. In this work, cooking additives were firstly applied in the sodium hydroxide pretreatment for improving the bioconversion of bamboo residues to monosaccharides. Meanwhile, steam explosion and sulfuric acid pretreatments were also carried out on the sample to compare their impacts on monosaccharides production. Results indicated that associating anthraquinone with sodium hydroxide pretreatment showed the best performance in improving the original carbohydrates recovery, delignification, enzymatic saccharification, and monosaccharides production. After consecutive pretreatment and enzymatic saccharification process, 347.49 g, 307.48 g, 142.93 g, and 87.15 g of monosaccharides were released from 1000 g dry bamboo residues pretreated by sodium hydroxide associating with anthraquinone, sodium hydroxide, steam explosion and sulfuric acid, respectively. The results suggested that associating cooking additive with sodium hydroxide is an effective pretreatment for bamboo residues to enhance enzymatic saccharification for monosaccharides production. PMID- 26133471 TI - Volatile fatty acids production from sewage organic matter by combined bioflocculation and anaerobic fermentation. AB - This work aims at exploring the feasibility of a combined process bioflocculation to concentrate sewage organic matter and anaerobic fermentation to produce volatile fatty acids (VFA). Bioflocculation, using a high-loaded aerobic membrane bioreactor (HL-MBR), was operated at an HRT of 1h and an SRT of 1 day. The HL-MBR process removed on average 83% of sewage COD, while only 10% of nitrogen and phosphorus was removed. During anaerobic fermentation of HL-MBR concentrate at an SRT of 5 days and 35 degrees C, specific VFA production rate of 282 mg VFA-COD/g VSS could be reached and consisted of 50% acetate, 40% propionate and 10% butyrate. More than 75% of sewage COD was diverted to the concentrate, but only 15% sewage COD was recovered as VFA, due to incomplete VSS degradation at the short treatment time applied. This shows that combined process for the VFA production is technologically feasible and needs further optimization. PMID- 26133472 TI - Combustion of hazardous biological waste derived from the fermentation of antibiotics using TG-FTIR and Py-GC/MS techniques. AB - The combustion characteristics for three kinds of antibiotics residue (AR) materials were investigated by TG-FTIR and Py-GC/MS technique. The TG results indicated that AR combustion involved three stages, and correlation between the H/C atomic ratio of the raw materials and peak temperature of weight loss for the second stage was obtained. The FTIR spectra identified evolving gaseous products as CO2, CH4, HCNO, NH3, HCN, and NO. An AR material with a low H/C ratio promoted the formation of CO2 and HCN, but suppressed the yields of NH3 and CH4. The Py GC/MS results suggested that abundant volatiles can be produced, including alkenes, benzene, phenols, furans, acid, and heterocyclic-N, nitrile-N and amine N compounds, and confirmed the FTIR absorption characteristics in the low temperature range. A possible pathway for the AR combustion was also tentatively presented. PMID- 26133473 TI - The correlation between cellulose allomorphs (I and II) and conversion after removal of hemicellulose and lignin of lignocellulose. AB - H2SO4, NaOH and H3PO4 were applied to decompose lignocellulose samples (giant reeds, pennisetum and cotton stalks) to investigate the correlation between cellulose allomorphs (cellulose I and II) and conversion of cellulose. The effect of removal of hemicellulose and lignin on the surface morphology, crystallinity index (CrI), cellulose allomorphs (cellulose I and II), and enzymatic hydrolysis under different pretreatments was also studied. CrI caused by H3PO4 pretreatment reached 11.19%, 24.93% and 8.15% for the three samples, respectively. Corn stalk showed highest conversion of cellulose among three samples, irrespective of the pretreatment used. This accounted for the widely use of corn stalk as the renewable crop substrate to synthesize biofuels like ethanol. CrI of cellulose I (CrI-I) negatively affects cellulose conversion but CrI of cellulose II (CrI-II) positively affects cellulose conversion. It contributes to make the strategy to transform cellulose I to cellulose II and enhancing enzymatic hydrolysis of lignocellulose. PMID- 26133474 TI - Microalgal cell disruption in a high-power ultrasonic flow system. AB - A 2-kW continuous ultrasonic flow system (UFS) was found effective in the disruption of two microalgal strains: Scenedesmus dimorphus and Nannochloropsis oculata. Compared to the control, cell debris concentration of UFS treatments increased up to 202% for S. dimorphus and 112% for N. oculata. Similarly, Nile red stained lipid fluorescence density (NRSLD) increased up to 59.5% and 56.3% for S. dimorphus and N. oculata, respectively. It was also found that increasing ultrasound intensity improved cell disruption efficiency indicated by up to 54% increase in NRSLFD of the two strains. Increasing sonication-processing time to 3 min resulted in 33.0% increase for S. dimorphus and 45.7% increase for N. oculata in NRSLFD compared to the control. Cell recirculation was found beneficial to cell disruption, however, higher initial cell concentration significantly reduced cell disruption efficiency, indicated by 98.2% decrease in NRSLFD per cell when initial cell concentration increased from 4.25 * 10(6) to 1.7 * 10(7)cells ml( 1). PMID- 26133475 TI - Methods coagulation/flocculation and flocculation with ballast agent for effective harvesting of microalgae. AB - The effects of coagulant (FeCl3.6H2O), various flocculants based on polyacrylamide (PAA), polyethylenoxide (PEO) and flocculated biomass as ballast agent, dosage and sedimental time on flocculation efficiency of harvesting Chlorella vulgaris GKV1 cultivated in a laboratory were investigated. The results of this work indicated that the flocculation efficiency achieved about 90% after 5 min of sedimentation when adding of coagulant and flocculant mixture (FeCl3 50 mg/l+PEO based Sibfloc-718 7.5 mg/l) or flocculant with ballast agent (Sibfloc 718 7.5 mg/l+10% flocculated biomass). PAA and PEO showed good flocculation efficiency at dosage of 0.025 and 0.015 g/l, respectively without pH adjustment. Finally, the most suitable flocculation method was discussed in this paper. PMID- 26133476 TI - Pyrolysis of microalgal biomass in carbon dioxide environment. AB - This work mechanistically investigated the influence of CO2 in the thermo chemical process of microalgal biomass (Chlorella vulgaris and Microcystis aeruginosa) to achieve a fast virtuous cycle of carbon via recovering energy. This work experimentally justified that the influence of CO2 in pyrolysis of microalgal biomass could be initiated at temperatures higher than 530 degrees C, which directly led to the enhanced generation of syngas. For example, the concentration of CO from pyrolysis of M. aeruginosa increased up to ~ 3000% at 670 degrees C in the presence of CO2. The identified universal influence of CO2 could be summarized by the expedited thermal cracking of VOCs evolved from microalgal biomass and by the unknown reaction between VOCs and CO2. This identified effectiveness of CO2 was different from the Boudouard reaction, which was independently occurred with dehydrogenation. Thus, microalgal biomass could be a candidate for the thermo-chemical process (pyrolysis and gasification). PMID- 26133477 TI - Biodiesel production process from microalgae oil by waste heat recovery and process integration. AB - In this work, the optimization of microalgae oil (MO) based biodiesel production process is carried out by waste heat recovery and process integration. The exergy analysis of each heat exchanger presented an efficient heat coupling between hot and cold streams, thus minimizing the total exergy destruction. Simulation results showed that the unit production cost of optimized process is 0.592$/L biodiesel, and approximately 0.172$/L biodiesel can be avoided by heat integration. Although the capital cost of the optimized biodiesel production process increased 32.5% and 23.5% compared to the reference cases, the operational cost can be reduced by approximately 22.5% and 41.6%. PMID- 26133478 TI - Prediction of moisture variation during composting process: A comparison of mathematical models. AB - This study was carried out to develop and compare three models for simulating the moisture content during composting. Model 1 described changes in water content using mass balance, while Model 2 introduced a liquid-gas transferred water term. Model 3 predicted changes in moisture content without complex degradation kinetics. Average deviations for Model 1-3 were 8.909, 7.422 and 5.374 kg m(-3) while standard deviations were 10.299, 8.374 and 6.095, respectively. The results showed that Model 1 is complex and involves more state variables, but can be used to reveal the effect of humidity on moisture content. Model 2 tested the hypothesis of liquid-gas transfer and was shown to be capable of predicting moisture content during composting. Model 3 could predict water content well without considering degradation kinetics. PMID- 26133479 TI - Using local lexicalized rules to identify heart disease risk factors in clinical notes. AB - Heart disease is the leading cause of death globally and a significant part of the human population lives with it. A number of risk factors have been recognized as contributing to the disease, including obesity, coronary artery disease (CAD), hypertension, hyperlipidemia, diabetes, smoking, and family history of premature CAD. This paper describes and evaluates a methodology to extract mentions of such risk factors from diabetic clinical notes, which was a task of the i2b2/UTHealth 2014 Challenge in Natural Language Processing for Clinical Data. The methodology is knowledge-driven and the system implements local lexicalized rules (based on syntactical patterns observed in notes) combined with manually constructed dictionaries that characterize the domain. A part of the task was also to detect the time interval in which the risk factors were present in a patient. The system was applied to an evaluation set of 514 unseen notes and achieved a micro-average F-score of 88% (with 86% precision and 90% recall). While the identification of CAD family history, medication and some of the related disease factors (e.g. hypertension, diabetes, hyperlipidemia) showed quite good results, the identification of CAD-specific indicators proved to be more challenging (F-score of 74%). Overall, the results are encouraging and suggested that automated text mining methods can be used to process clinical notes to identify risk factors and monitor progression of heart disease on a large-scale, providing necessary data for clinical and epidemiological studies. PMID- 26133480 TI - Emerging medical informatics with case-based reasoning for aiding clinical decision in multi-agent system. AB - This research aims to depict the methodological steps and tools about the combined operation of case-based reasoning (CBR) and multi-agent system (MAS) to expose the ontological application in the field of clinical decision support. The multi-agent architecture works for the consideration of the whole cycle of clinical decision-making adaptable to many medical aspects such as the diagnosis, prognosis, treatment, therapeutic monitoring of gastric cancer. In the multi agent architecture, the ontological agent type employs the domain knowledge to ease the extraction of similar clinical cases and provide treatment suggestions to patients and physicians. Ontological agent is used for the extension of domain hierarchy and the interpretation of input requests. Case-based reasoning memorizes and restores experience data for solving similar problems, with the help of matching approach and defined interfaces of ontologies. A typical case is developed to illustrate the implementation of the knowledge acquisition and restitution of medical experts. PMID- 26133481 TI - Using Analysis of Governance to Unpack Community-Based Conservation: A Case Study from Tanzania. AB - Community-based conservation policies and programs are often hollow with little real devolution. But to pass a judgment of community-based or not community-based on such initiatives and programs obscures what is actually a suite of attributes. In this paper, we analyze governance around a specific case of what is nominally community-based conservation-Ikona Wildlife Management Area (WMA) in Tanzania using two complementary sets of criteria. The first relates to governance "powers": planning powers, regulatory powers, spending powers, revenue-generating powers, and the power to enter into agreements. The second set of criteria derive from the understanding of governance as a set of social functions: social coordination, shaping power, setting direction, and building community. The analysis helps to detail ways in which the Tanzanian state through policy and regulations has constrained the potential for Ikona WMA to empower communities and community actors. Although it has some features of community-based conservation, community input into how the governance social functions would be carried out in the WMA was constrained from the start and is now largely out of community hands. The two governance powers that have any significant community based flavor-spending powers and revenue-generating powers-relate to the WMA's tourism activities, but even here the picture is equivocal at best. The unpacking of governance that we have done, however, reveals that community empowerment through the processes associated with creating and recognizing indigenous and community-conserved areas is something that can be pursued through multiple channels, some of which might be more strategic than others. PMID- 26133482 TI - Information Needs Assessment for Coastal and Marine Management and Policy: Ecosystem Services Under Changing Climatic, Land Use, and Demographic Conditions. AB - Changing climatic, demographic, and land use conditions are projected to alter the provisioning of ecosystem services in estuarine, coastal, and nearshore marine ecosystems, necessitating mitigation and adaptation policies and management. The current paradigm of research efforts occurring in parallel to, rather than in collaboration with, decision makers will be insufficient for the rapid responses required to adapt to and mitigate for projected changing conditions. Here, we suggest a different paradigm: one where research begins by engaging decision makers in the identification of priority data needs (biophysical, economic, and social). This paper uses synthesized interview data to provide insight into the varied demands for scientific research as described by decision makers working on coastal issues in Oregon, USA. The findings highlight the need to recognize (1) the differing framing of ecosystem services by decision makers versus scientists; and (2) the differing data priorities relevant to inland versus coastal decision makers. The findings further serve to highlight the need for decision makers, scientists, and funders to engage in increased communication. This research is an important first step in advancing efforts toward evidence-based decision making in Oregon and provides a template for further research across the US. PMID- 26133483 TI - Arylene ethynylene macrocycles: from molecular hosts to components of high performance supramolecular architectures. AB - Supramolecular chemistry of conjugated and conformationally rigid arylene ethynylene macrocycles (AEMs) has been the subject of increasing recent interest. AEMs are suited to function as supramolecular building blocks and hosts for small molecular guests thanks to their well-defined, non-collapsible central cavities and the potential for long range ordering through intermolecular pi-stacking. Their syntheses are highly modular--albeit typically lengthy--allowing access to a great structural variety of AEM candidates for applications as carbon-rich mesogens and ligands in liquid crystals, nanoporous solids, molecular electronics, and chemical sensors. In this perspective, we highlight our recent work on the inclusion complexes and porous materials constructed from AEMs. Through this prism, we reflect on the recent advances and the remaining challenges in the supramolecular chemistry of AEMs. PMID- 26133484 TI - Use of re-esterified palm oils, differing in their acylglycerol structure, in fattening pig diets. AB - Re-esterified oils are new fat sources obtained from the chemical esterification of acid oils with glycerol (both economically interesting by-products from oil refining and biodiesel industries, respectively). The different fatty acid (FA) positional distribution and acylglycerol composition of re-esterified oils may enhance the apparent absorption of saturated fatty acids (SFA) and, therefore, their overall nutritive value, which might lead to an increased deposition of SFA. The aim of the present study was to investigate the potential use of re esterified palm oils, in comparison with their corresponding acid and native oils in fattening pig diets, studying their effects on fatty acid apparent absorption, acylglycerol and free fatty acid (FFA) composition of feces, growth performance, carcass-fat depots and fatty acid composition of backfat. Seventy-two crossbred boars and gilts (average weight of 24.7 +/- 2.55 kg) were blocked by initial BW (nine blocks of BW for each gender), housed in adjacent individual boxes, and fed one of the four dietary treatments, which were the result of a basal diet supplemented with 4% (as-fed basis) of native palm oil (PN), acid palm oil (PA), re-esterified palm oil low in mono- and diacylglycerols (PEL), or re-esterified palm oil high in mono- and diacylglycerols (PEH). Regarding results from the digestibility balance, PA and PN showed similar apparent absorption coefficients (P>0.05), despite the high, FFA content of the former. However, re-esterified palm oils (both PEL and PEH) showed a higher apparent absorption of total FA than did their corresponding native and acid oils (P0.05). We conclude that re esterified oils are interesting fat sources to be considered in fattening pigs. PMID- 26133485 TI - Highly Active Biocatalytic Coatings from Protein-Polymer Diblock Copolymers. AB - A method for fabricating nanostructured biocatalysts using bioconjugate block copolymer self-assembly is demonstrated, yielding very high protein loadings and activity per unit area, compared to more-established enzyme encapsulation methods. Self-assembled heterogeneous biocatalysts are fabricated by flow coating myoglobin-b-poly(N-isopropylacrylamide) (myoglobin-PNIPAM) block copolymers onto solid supports, and films are stabilized by lightly cross-linking with glutaraldehyde. The conjugates form weakly ordered, nonbirefringent micellar and lamellar assemblies in concentrated solution and disordered but micro-phase separated structures in thin solid films. The low diffusion resistance in the bioconjugate film imparted by the water-swollen PNIPAM nanostructures, the high enzyme density within the film, and high retention of protein activity results in extremely high catalytic activity: 5-10 times greater than catalysts fabricated using other well-established methods. PMID- 26133486 TI - Treatment with PPARdelta agonist alleviates non-alcoholic fatty liver disease by modulating glucose and fatty acid metabolic enzymes in a rat model. AB - Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition which is associated with certain features of metabolic syndrome and insulin resistance. Peroxisome proliferator-activated receptor (PPAR)delta is an important regulator of energy metabolism and insulin resistance in diabetes. However, the function of PPARdelta in NAFLD has not yet been fully elucidated. In the present study, in order to explore the function of PPARdelta in NAFLD, we created a rat model of NALFD induced by a high-fat diet (HFD) and treated the rats with GW501516, a PPARdelta agonist. We found that the lipid levels decreased, and hepatocellular ballooning and inflammatory cell infiltration were also significantly decreased following treatment of the rats with GW501516 compared to the untreated rats. Treatment with GW501516 also significantly decreased the homeostasis model assessment of insulin resistance (HOMA-IR) index, as well as the low-density lipoprotein (LDL) levels. In addition, treatment with GW501516 increased the levels of insulin-like growth factor-1 (IGF-1) and high density lipoprotein (HDL) compared to the HFD group. Furthermore, the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) in the HFD group were all restored to the normal control levels following treatment with GW501516. RT-qPCR and immunohistochemical staining revealed that the expression levels of sterol regulatory element binding protein-1c (SREBP-1c) and glucose transporter 2 (GLUT-2) were both restored to normal control levels following treatment with GW501516. Also, the levels of enzymes related to lipid metabolism were increased following treatment with GW501516. In conclusion, our findings demonstrate that treatment with GW501516 alleviates NAFLD by modulating glucose and fatty acid metabolism. PMID- 26133487 TI - Creating One's Reality: The Interaction of Politics Perceptions and Enactment Behavior. AB - The current study investigated the previously unexamined relationship between politics perceptions and employee enactment behavior. Consistent with previous job stress and sense-making research, we hypothesized that individuals reporting low levels of enactment behaviors would be more adversely affected by politics perceptions than those who engaged in high levels of enactment behavior. Results across two samples provided strong support for the hypothesized relationships. Specifically, employees who reported low levels of enactment behavior experienced less satisfaction, less person-environment fit, and reported lower levels of effort when faced with highly political environments. Conversely, levels of satisfaction and person-environment fit perceptions of individuals reporting high levels of enactment behaviors were largely unaffected by highly political contexts. Implications of these findings, strengths and limitations, and avenues for future research are provided. PMID- 26133489 TI - Dimensionless equations to describe microalgal growth in a planar cultivation system. AB - OBJECTIVES: To develop dimensionless equations to describe microalgal growth in planar photobioreactor or raceway pond systems that are generalized to all phototrophic species and reactor length scales. RESULTS: Expressions for biomass growth and mean light intensity within a nutrient replete, well-mixed, phototrophic cell culture in a planar cultivation system were developed in terms of dimensionless variables for biomass, time and light intensity, plus two new dimensionless parameters. The first dimensionless parameter represents a species specific physiological characteristic based on maximum growth rate and cell maintenance, while the second represents the light input. Optimal biomass productivities and photosynthetic conversion efficiencies are easily determined from the dimensionless expressions and system-specific performances can be easily determined by back substituting with the relevant cell culture and photobioreactor parameters. CONCLUSION: The dimensionless expressions are useful for understanding and determining the relevant bioprocess parameters in a generalized form applicable to all strains and reactor length scales. PMID- 26133488 TI - Attributing discrimination to weight: associations with well-being, self-care, and disease status in patients with type 2 diabetes mellitus. AB - This study examined the association between attributing self-reported discrimination to weight and diabetes outcomes (glycemic control, diabetes related distress, and diabetes self-care). A community dwelling sample of 185 adults (mean age 55.4; 80 % White/Caucasian 65 % female) with poorly controlled type 2 diabetes (HbA1c level >= 7.5 %) provided demographic and several self report measures (including diabetes-related distress, diabetes self-care activities, discrimination, and attributions of discrimination), and had height, weight, and glycated hemoglobin (HbA1c) assessed by trained research staff as part of a larger research study. Individuals who attributed self-reported discrimination to weight had significantly higher HbA1c levels, higher levels of diabetes-related distress, and worse diabetes-related self-care behaviors (general diet, exercise, and glucose testing). These relationships persisted even when controlling for BMI, overall discrimination, depressive symptoms, and demographic characteristics. Results indicate that the perception of weight stigma among individuals with type 2 diabetes is strongly associated with a range of poor diabetes outcomes. Efforts to reduce exposure to and/or teach adaptive coping for weight stigma may benefit patients with type 2 diabetes. PMID- 26133491 TI - Acylation of (Hetero)Arenes through C-H Activation with Aroyl Surrogates. AB - In this Minireview, the major achievements in the acylation of arenes and heteroarenes by C-H activation with aroyl groups are summarized and discussed. As the products are carbonyl-containing compounds that are typical products from carbonylation chemistry, the possible inspirations for these reactions are also discussed, as are mechanistic issues and possible problems for carbonylative diaryl ketone synthesis by C-H activation. PMID- 26133490 TI - Trastuzumab and docetaxel in a preclinical organotypic breast cancer model using tissue slices from mammary fat pad: Translational relevance. AB - With the ever-increasing number of drugs approved to treat cancers, selection of the optimal treatment regimen for an individual patient is challenging. Breast cancer complexity requires novel predictive methods and tools. In the present study, we set up experimental conditions to obtain an 'ex vivo' organotypic culture from xenotransplanted mice aiming at recapitulating the human clinical condition. The effect of trastuzumab (large biological molecule) and docetaxel (small chemical entity) was subsequently investigated on this organotypic model and compared with in vivo and in vitro activity on tumor cells. Tissue slices of 200 um were obtained from mammary fat pad of SCID mice xenotransplanted with human MCF-7 breast cancer cells. Viability and proliferation were evaluated by 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) colorimetric assay and Ki-67 immunohistochemistry,and apoptosis by cleaved caspase-3 immunohistochemistry. In vivo antitumor activity of trastuzumab and docetaxel was determined by caliper measurement of tumor volume and Ki-67 expression on explanted masses by immunohistochemistry. A Teflon support and normoxia were necessary experimental conditions to obtain high viability of excised breast cancer infiltrated mammary fat pad slices upon 48 h cultivation, as shown by MTT proliferation assay, and Ki-67 expression. Breast cancer tissue slices treated for 48 h with trastuzumab or docetaxel showed a significant dose-dependent reduction of viability by MTT assay. Consistently, both drugs down-modulated Ki 67 and increased cleaved caspase-3. Tumor masses collected from docetaxel- or trastuzumab-treated mice showed a similar reduction of proliferation markers. By contrast, MCF-7 cell cultures were significantly inhibited by docetaxel but not by trastuzumab. Tumor tissue slices represent a more predictive experimental cancer model compared to cell cultures for both small and large molecule antitumor efficacy. This observation supports the relevance of microenvironment in the overall tumor biology and response to therapeutics. PMID- 26133495 TI - Vulvar Intraepithelial Neoplasia (VIN) and Condylomata. AB - Human papillomavirus (HPV) infection of the lower genital tract is common and its effects are variable. The majority of infections are transient and the related pathology is self-resolving. Condyloma accuminatum is caused predominantly by HPV 6, 11 and can be managed with medical or surgical therapy. Vulvar intraepithelial neoplasia is a treatable precursor to vulvar cancer with 2 main forms: one related to HPV and the other to chronic vulvar inflammatory conditions. It may be treated medically, surgically, or potentially via the use of therapeutic HPV vaccines. Preventive utilization of a quadrivalent HPV vaccine has the potential to decrease HPV-related lower genital disease burden substantially. PMID- 26133496 TI - First-trimester Ultrasound and Aneuploidy Screening in Multifetal Pregnancies. AB - First-trimester ultrasound provides valuable information to help optimize the management of multifetal pregnancies. First trimester ultrasound the use of ultrasound and screening for aneuploidy has been well studied in singleton pregnancies. While evidence supporting the use of ultrasound in multiple gestations is well established, aneuploidy screening continues to evolve and its role in the prenatal setting has been less well studied. We review the importance of early first trimester ultrasound in assessing gestational age and chorionicity and early identification of anomalies, and review the various methods and limitations of aneuploidy screening and invasive diagnostic procedures in multiples. PMID- 26133497 TI - Hydrodynamic instabilities in shear flows of dry cohesive granular particles. AB - We extend the dynamic van der Waals model introduced by A. Onuki [Phys. Rev. Lett., 2005, 94, 054501] to the description of cohesive granular flows under a plane shear to study their hydrodynamic instabilities. By numerically solving the dynamic van der Waals model, we observed various heterogeneous structures of density fields in steady states, where the viscous heating is balanced with the energy dissipation caused by inelastic collisions. Based on the linear stability analysis, we found that the spatial structures are determined by the mean volume fraction, the applied shear rate, and the inelasticity, where the instability is triggered if the system is thermodynamically unstable, i.e. the pressure, p, and the volume fraction, phi, satisfy ?p/?phi < 0. PMID- 26133498 TI - Precise risk factors for Osgood-Schlatter disease. AB - INTRODUCTION: A number of studies have examined the risk factors for Osgood Schlatter disease (OSD). Studies on risk factors have not necessarily accurately demonstrated the risk factors of this disease because they were not prospective cohort studies or the populations in the studies were not categorized by the skeletal maturation of the tibial tuberosity. We can identify the precise risk factors for OSD by performing a prospective cohort study of a group of asymptomatic patients in particular times of adolescent using ultrasonography. In the present study, we aimed to investigate the precise risk factors for OSD. METHODS: For all examinations, we used a 3-stage classification for tibial tuberosity development observed on ultrasonography: sonolucent (stage S), individual (stage I), and connective stages (stage C). Among 150 players with 300 knees, we included 37 male players with 70 knees at asymptomatic stage I on the first examination. We re-examined the included knees 1 year after the first examination and compared 10 knees with OSD (OSD group) and 60 knees without OSD (control group). Height, body weight, body mass index, tightness of the quadriceps femoris and hamstring muscles, muscle strength during knee extension, and flexion were assessed during the first medical examination. RESULTS: The incidence of OSD was 14.3 % in this 1-year cohort study. A significant difference was found in body weight, quadriceps muscle tightness, and muscle tightness and strength during knee extension between the 2 groups. The precise risk factors for OSD were increased, namely the quadriceps femoris muscle tightness and strength during knee extension and flexibility of the hamstring muscles, using logistic regression analysis. CONCLUSIONS: This information may be useful for teaching quadriceps stretching in preadolescent male football players with stage I. PMID- 26133499 TI - JAMA PATIENT PAGE. Suntan and Sunburn. PMID- 26133500 TI - Indifference of marmosets with prenatal valproate exposure to third-party non reciprocal interactions with otherwise avoided non-reciprocal individuals. AB - Autism is characterized by deficits in social interaction and social recognition. Although animal models of autism have demonstrated that model animals engage less in social interaction or attend less to conspecifics than control animals, no animal model has yet replicated the deficit in recognition of complex social interaction as is seen in humans with autism. Here, we show that marmosets discriminated between human actors who reciprocated in social exchanges and those who did not; however, marmosets with foetal exposure to valproic acid (VPA marmosets) did not. In the reciprocal condition, two actors exchanged food equally, while in the non-reciprocal condition, one actor (non-reciprocator) ended up with all food and the other actor with none. After observing these exchanges, the control marmosets avoided receiving food from the non-reciprocator in the non-reciprocal condition. However, the VPA marmosets did not show differential preferences in either condition, suggesting that the VPA marmosets did not discriminate between reciprocal and non-reciprocal interactions. These results indicate that normal marmosets can evaluate social interaction between third-parties, while the VPA marmosets are unable to recognize whether an individual is being reciprocal or not. This test battery can serve as a useful tool to qualify primate models of autism. PMID- 26133501 TI - Modeling Opponents in Adversarial Risk Analysis. AB - Adversarial risk analysis has been introduced as a framework to deal with risks derived from intentional actions of adversaries. The analysis supports one of the decisionmakers, who must forecast the actions of the other agents. Typically, this forecast must take account of random consequences resulting from the set of selected actions. The solution requires one to model the behavior of the opponents, which entails strategic thinking. The supported agent may face different kinds of opponents, who may use different rationality paradigms, for example, the opponent may behave randomly, or seek a Nash equilibrium, or perform level-k thinking, or use mirroring, or employ prospect theory, among many other possibilities. We describe the appropriate analysis for these situations, and also show how to model the uncertainty about the rationality paradigm used by the opponent through a Bayesian model averaging approach, enabling a fully decision theoretic solution. We also show how as we observe an opponent's decision behavior, this approach allows learning about the validity of each of the rationality models used to predict his decision by computing the models' (posterior) probabilities, which can be understood as a measure of their validity. We focus on simultaneous decision making by two agents. PMID- 26133502 TI - Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells. AB - Nrf2 is a redox sensitive transcription factor that is involved in the co ordinated transcription of genes involved in redox homeostasis. But the role of Nrf2 in DNA repair is not investigated in detail. We have employed A549 and MCF7 cells to study the role of Nrf2 on DNA repair by inhibiting Nrf2 using all-trans retinoic acid (ATRA) or by knock down approach prior to radiation exposure (4 Gy). DNA damage and repair analysis was studied by gammaH2AX foci formation and comet assay. Results suggested that the inhibition of Nrf2 in A549 or MCF7 cells led to significant slowdown in DNA repair as compared to respective radiation controls. The persistence of residual DNA damage even in the presence of free radical scavenger N-acetyl cysteine, suggested that the influence of Nrf2 on DNA repair was not linked to its antioxidant functions. Further, its influence on non homologous end joining repair pathway was studied by inhibiting both Nrf2 and DNA PK together. This led to synergistic reduction of survival fraction, indicating that Nrf2 may not be influencing the NHEJ pathway. To investigate the role of homologous recombination repair (HR) pathway, RAD51 foci formation was monitored. There was a significant reduction in the foci formation in cells treated with ATRA or shRNA against Nrf2 as compared to their respective radiation controls. Further, Nrf2 inhibition led to significant reduction in mRNA levels of RAD51. BLAST analysis was also performed on upstream regions of DNA repair genes to identify antioxidant response element and found that many repair genes that are involved in HR pathway may be regulated by Nrf2. Together, these results suggest the involvement of Nrf2 in DNA repair, a hitherto unknown function of Nrf2, putatively through its influence on HR pathway. PMID- 26133503 TI - Relative quantitation of multi-antennary N-glycan classes: combining PGC-LC-ESI MS with exoglycosidase digestion. AB - In the search for N-glycan disease biomarkers current glycoanalytical methods may not be revealing a complete picture of precious samples, and we may be missing valuable structural information that fall outside analysis windows. We report a targeted strategy combining PGC-LC-ESI-MS with exoglycosidases to improve the relative quantitation of tri and tetra-antennary glycan classes. PMID- 26133504 TI - Nanoscopic yttrium oxide fluorides: non-aqueous fluorolytic sol-gel synthesis and structural insights by 19F and 89Y MAS NMR. AB - Nanoscopic yttrium acetate fluorides Y(CH(3)COO)(3-z)F(z) and yttrium oxide fluorides YO(3-z)/(2)F(z )were prepared with tunable Y/F molar ratios via the fluorolytic sol-gel route. All samples were characterized by X-ray diffraction, elemental analysis and thermal analysis. In addition, local structures of all samples were studied by (19)F MAS, (19)F-(89)Y CP MAS and (1)H-(89)Y CP MAS NMR spectroscopy and the respective chemical shifts are given. For both classes of compounds, only the fluorination using one equivalent of F (z = 1) leads to defined, well crystalline matrices: yttrium acetate fluoride Y(CH(3)COO)(2)F and r-YOF. PMID- 26133505 TI - International collaborative research on infectious diseases by Japanese universities and institutes in Asia and Africa, with a special emphasis on J GRID. AB - In developed countries including Japan, malignant tumor (cancer), heart disease and cerebral apoplexy are major causes of death, but infectious diseases are still responsible for a high number of deaths in developing countries, especially among children aged less than 5 years. World Health Statistics published by WHO reports a high percentage of mortality from infectious diseases in children, and many of these diseases may be subject to transmission across borders and could possibly invade Japan. Given this situation, the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan initiated Phase I of the Program of Founding Research Centers for Emerging and Reemerging Infectious Disease, which ran from FY 2005 to 2009, and involved 8 Japanese universities and 2 research centers. The program was established for the following purposes: 1) creation of a domestic research structure to promote the accumulation of fundamental knowledge about infectious diseases, 2) establishment of 13 overseas research collaboration centers in 8 countries at high risk of emerging and reemerging infections and at which Japanese researchers are stationed and conduct research in partnership with overseas instructors, 3) development of a network among domestic and overseas research centers, and 4) development of human resources. The program was controlled under MEXT and managed by the RIKEN Center of Research Network for Infectious Diseases (Riken CRNID). Phase II of the program was set up as the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID), and has been running in FY 2010-2014. Phase III will start in April 2015, and will be organized by the newly established Japanese governmental organization "Japan Agency for Medical Research and Development (AMED)", the so-called Japanese style NIH. The Collaborative Research Center of Okayama University for Infectious Diseases in India (CRCOUI) was started up in 2007 at the National Institute of Cholera and Enteric Disease, Kolkata, India. Major projects of CRCOUI are concerned with diarrheal diseases such as, 1) active surveillance of diarrheal patients, 2) development of dysentery vaccines, 3) viable but nonculturable (VBNC) Vibrio cholerae, and 4) pathogenic mechanisms of various diarrhogenic microorganisms. This review article outlines project of J GRID and CRCOUI which the authors carried out collaboratively with NICED staff members. PMID- 26133506 TI - Killing effect of peppermint vapor against pink-slime forming microorganisms. AB - The killing effect of peppermint vapor (PMV) against pink-slime forming microorganisms, Methylobacterium mesophilicum as a bacterium and Rhodotorula mucilaginosa as a yeast, was investigated by the agar vapor assay. In this method, microbial cells were spread over the agar surface exposed to PMV in a petri dish, and then transferred into a recovery liquid. When 60MUl of the peppermint liquid was added to a paper disc, a marked killing effect of PMV was observed after 48h against M. mesophilicum and after 168h against R. mucilaginosa. M. mesophilicum and R. mucilaginosa were found to be more resistant to PMV than Escherichia coli and Candida albicans, used as reference microorganisms, respectively. With the addition of 0.03% sodium pyruvate as a hydrogen peroxide scavenger in agar, the killing effect of PMV against E. coli and C. albicans was decreased, whereas it was little changed against M. mesophilicum and R. mucilaginosa. In fact, the properties of the killing effect of hydrogen peroxide solution at 0.2-1.0mM was in accord with those of PMV. M. mesophilicum and R. mucilaginosa were more resistant to the oxidant than E. coli and C. albicans, respectively. Results obtained suggested that reactive oxygen species (ROS) may be involved in the killing action of PMV and therefore pink slime formers are more resistant to PMV than non-pink-slime formers because of the presence of carotenoids as an antioxidant in cells. We also suggest that the use of PMV appeared to be a potential tool for the control of pink-slime forming microorganisms occurring in wet areas of houses such as the bathroom and washing room. PMID- 26133507 TI - Rapid and simple colorimetric detection of Escherichia coli O157:H7 in apple juice using a novel recombinant bacteriophage-based Method. AB - In this study, a bacteriophage-based method for the colorimetric detection of E. coli O157:H7 in apple juice was investigated. Firstly, a gene encoding Cytochrome c Peroxidase (CCP) chromogenic enzyme was inserted into a wild type PP01 phage genome to construct the recombinant PP01ccp phage that was used in the production of the chromogenic enzyme through specific infection into E. coli O157:H7. The method was then examined in the colorimetric detection of E. coli O157:H7 in broth, and the appearance of E. coli O157:H7 in broth was confirmed by the color change after a few minutes of the enzyme assay. Secondly, the method was investigated in the colorimetric detection of E. coli O157:H7 in apple juice. A low E. coli O157:H7 concentration as 1 CFU mL(-1) was detected in 15 h that was in a shorter time than in previous bioluminescence phage-based methods. Moreover, the method is much simpler compared to other previous phage-based methods since it enables detection without the need for expensive apparatus. PMID- 26133508 TI - Presence of extracellular NAD(+) and NADH in cultures of wood-degrading fungi. AB - Our previous studies indicated that extracellular glycoproteins produced by some white-rot and brown-rot basidiomycetous fungi reduce Fe(III) to Fe(II) and O2 to H2O2 and produce hydroxyl radicals. The continuous generation of hydroxyl radicals requires a constant supply of O2 and an electron donor for the reduction of oxidized forms of the glycoproteins to the reduced forms. However, electron donors for this reaction, such as NADH, have not been identified. In this study, the amounts of the extracellular pyridine coenzymes, NAD(+) and NADH, were measured in agar cultures of four white-rot fungi, one brown-rot fungus, and three soft-rot fungi. The sums of NAD(+) and NADH detected in wood-containing cultures of all five basidiomycetes were greater than those in glucose cultures. The amounts of NAD(+) were higher than those of NADH in all wood-containing cultures except that of Irpex lacteus, and NAD(+) was greater than NADH in all glucose cultures except that of Fomitopsis palustris. Significant amounts of pyridine coenzymes were present in glucose and wood-containing cultures of the three soft-rot fungi. The non-wood-degrading fungus, Penicillium funiculosum, did not produce NAD(+) or NADH in either glucose or wood-containing cultures. The extracellular pyridine coenzyme levels were relatively high compared to the rates of extracellular hydroxyl radical generation in wood-degrading fungal cultures. Thus, white-, brown-, and soft-rot fungi produce pyridine coenzymes that could serve as electron donors for the production of hydroxyl radicals during wood degradation. PMID- 26133509 TI - Novel toxicity of Bacillus thuringiensis strains against the melon fruit fly, Bactrocera cucurbitae (Diptera: Tephritidae). AB - Bactrocera cucurbitae (melon fruit fly) is one of the most detrimental vegetable damaging pests in Bangladesh. The toxicity of Bacillus thuringiensis (Bt) has been reported against a few genera of Bactrocera in addition to numerous other insect species. Bt strains, harbouring cry1A-type genes were, therefore, assayed in vivo against the 3(rd) instar larvae of B. cucurbitae in this study. The biotype-based prevalence of cry1 and cry1A genes was calculated to be 30.8% and 11.16%, respectively, of the test strains (n=224) while their prevalence was greatest in biotype kurstaki. Though three indigenous Bt strains from biotype kurstaki with close genetic relationship exhibited higher toxicity, maximum mortalities were recorded for Btk HD-73 (96%) and the indigenous Bt JSc1 (93%). LC50 and LC99 values were determined to be 6.81 and 8.32 for Bt JSc1, 7.30 and 7.92 for Bt SSc2, and 6.99 and 7.67 for Btk HD-73, respectively. The cause of toxicity and its variation among the strains was found to be correlated with the synergistic toxic effects of cry1, cry2, cry3 and cry9 gene products, i.e. relevant Cry proteins. The novel toxicity of the B. thuringiensis strains against B. cucurbitae revealed in the present study thus will help in developing efficient and eco-friendly control measures such as Bt biopesticides and transgenic Bt cucurbits. PMID- 26133510 TI - Utilization of coconut oil cake for the production of lipase using Bacillus coagulans VKL1. AB - The overproduction of enzymes was performed by manipulating the medium components. In our study, solvent-tolerant thermophilic lipase-producing Bacillus coagulans was isolated from soil samples and a stepwise optimization strategy was employed to increase the lipase production using coconut oil cake basal medium. In the first step, the influence of pH, temperature, carbon source, nitrogen source and inducers on lipase activity was investigated by the One-Factor-At-A Time (OFAT) method. In the second step, the three significant factors resulted from OFAT were optimized by the statistical approach (CCD).The optimum values of olive oil (0.5%), Tween 80 (0.6%) and FeSO4 (0.05%) was found to be responsible for a 3.2-fold increase in the lipase production identified by Central Composite Design. PMID- 26133511 TI - Formation and elution of toxic compounds from gamma-ray-sterilized medical products and the Ames test of eluted components. AB - No formation of N,N'-methylene dianiline (MDA) was observed in chain-extended thermoplastic polyurethane (PU) when sterilized by autoclaving or gamma-ray irradiation. No formation of MDA was observed in nonchain-extended thermoplastic PU when sterilized by gamma-ray irradiation. Less than 1 ppm of MDA was produced in nonchain-extended thermoplastic PU subjected to autoclave sterilization. Autoclave sterilization did not produce MDA in thermosetting PU potting material. MDA formation in potting material was promoted by gamma-ray irradiation and increased with increasing irradiation doses at a quadratic equation of regression. MDA formation at 100 kGy irradiation amounted to a few ppm and less than one ppm at 25 kGy irradiation: therefore, the potential risk to human recipients was not significant. The elution of compounds other than MDA from potting material was more problematic. Solvent extracts from potting material showed mutagenicity in the absence of metabolic activity (S9Mix). MDA showed mutagenicity in the presence of metabolic activity, therefore MDA was not the major mutagenic candidate. The chemical and biological characteristics of the specific mutagens should be identified in a further study. The lack of MDA formation and a smaller presence of mutagens in autoclave-sterilized potting material indicated that autoclave sterilization was preferable if the material is able to tolerate heating. PMID- 26133512 TI - Bacterial contamination in cold water samples obtained from water dispensers. AB - We carried out a basic study in order to evaluate the bacterial contamination in water dispensers. Water samples were obtained from water dispensers from October 2012 to November 2013, and standard plate counts (at 36C, 24 h) of the samples, as well as heterotrophic plate counts (at 25C, 7 d), were estimated with the standard methods for the examination of drinking water in Japan. Standard plate counts exceeding the water-quality standard (1.0*10(2) CFU/ml) were observed in 42 of the 140 samples (30.0%), with a maximum detected bacterial count of 2.1*10(5) CFU/ml. The rate of the standard plate counts exceeding the water quality standard tended to be higher when using a one-way type method or water dispensers with natural water. Ralstonia spp. was most commonly isolated, and Pseudomonas aeruginosa was isolated in a few cases. Some opportunistic pathogens were also isolated, suggesting that we should be more concerned about bacterial contamination in cold water supplied from water dispensers. PMID- 26133513 TI - Heated scallop-shell powder treatment for deactivation and removal of Listeria sp. biofilm formed at a low temperature. AB - The ability of heated scallop-shell powder (HSSP) to work against Listeria sp. biofilm formed at a low temperature was investigated. A biofilm of L. innocua ATCC 33090 was grown on a glass plate at 15C for 15 days, then immersed in HSSP slurry. Following treatment, the disinfection ability of the HSSP against the biofilm was non-destructively quantified by conductimetric assay. The biofilm grown at 15C was less sensitive than that grown at 37C to HSSP treatment and alkaline treatment. The biofilm grown at 15C was completely deactivated by 30 min of HSSP treatment (10 mg/mL, pH 12.5). In contrast, after 30 min treatment with alkaline solution at pH 12.5 or sodium hypochlorite (100 ppm), the activity was reduced by only one order of magnitude. The disinfection efficacy of HSSP (10 mg/mL) against L. innocua is similar to or higher than that of sodium hypochlorite (200 ppm). Fluorescence microscopy validated the results of the conductimetric assay. Therefore, HSSP treatment is a potentially powerful alternative control agent against Listeria sp. biofilms that present hazards in the food industry. PMID- 26133515 TI - Cardiac Assist Devices and Hemodialysis Catheter Procedures - What Do the Nephrologists Need to Know? AB - The use of ventricular assist devices (VAD) and total artificial heart (TAH) is increasing rapidly, and a large proportion of these device recipients already have or will develop severe renal dysfunction at the time of device implantation. As a consequence, nephrologists are becoming more and more involved in the care of this challenging population. As nephrologists take upon themselves many aspects of dialysis vascular access care, they need to be familiar with the special circumstances of performing hemodialysis catheter procedures in these patients. This review describes the important characteristics of these devices that have serious implications for the technique of placing or replacing dialysis catheters. These implications apply for both tunneled and nontunneled dialysis catheters and so concern all nephrologists, not only the interventionalists. We describe the important anatomical factors, anticoagulation management, device management, vascular access management and technical considerations of placing or replacing tunneled and nontunneled hemodialysis catheters from the perspective of a nephrologist establishing and maintaining lifesaving dialysis vascular access. Without a good understanding of these devices, serious consequences such as VAD rotor damage or blockage, or artificial heart valve blockage or damage can occur. These artificial devices are lifesaving, and any such complication is unacceptable. This review describes steps to minimize the risks. PMID- 26133516 TI - CDC releases a National Public Health Action Plan for the Detection, Prevention, and Management of Infertility. PMID- 26133514 TI - Short-term Periodization Models: Effects on Strength and Speed-strength Performance. AB - Dividing training objectives into consecutive phases to gain morphological adaptations (hypertrophy phase) and neural adaptations (strength and power phases) is called strength-power periodization (SPP). These phases differ in program variables (volume, intensity, and exercise choice or type) and use stepwise intensity progression and concomitant decreasing volume, converging to peak intensity (peaking phase). Undulating periodization strategies rotate these program variables in a bi-weekly, weekly, or daily fashion. The following review addresses the effects of different short-term periodization models on strength and speed-strength both with subjects of different performance levels and with competitive athletes from different sports who use a particular periodization model during off-season, pre-season, and in-season conditioning. In most periodization studies, it is obvious that the strength endurance sessions are characterized by repetition zones (12-15 repetitions) that induce muscle hypertrophy in persons with a low performance level. Strictly speaking, when examining subjects with a low training level, many periodization studies include mainly hypertrophy sessions interspersed with heavy strength/power sessions. Studies have demonstrated equal or statistically significant higher gains in maximal strength for daily undulating periodization compared with SPP in subjects with a low to moderate performance level. The relatively short intervention period and the lack of concomitant sports conditioning call into question the practical value of these findings for competitive athletes. Possibly owing to differences in mesocycle length, conditioning programs, and program variables, competitive athletes either maintained or improved strength and/or speed-strength performance by integrating daily undulating periodization and SPP during off season, pre-season and in-season conditioning. In high-performance sports, high repetition strength training (>15) should be avoided because it does not provide an adequate training stimulus for gains in muscle cross-sectional area and strength performance. High-volume circuit strength training performed over 2 years negatively affected the development of the power output and maximal strength of the upper extremities in professional rugby players. Indeed, meta analyses and results with weightlifters, American Football players, and throwers confirm the necessity of the habitual use of >=80% 1 RM: (1) to improve maximal strength during the off-season and in-season in American Football, (2) to reach peak performance in maximal strength and vertical jump power during tapering in track-and-field, and (3) to produce hypertrophy and strength improvements in advanced athletes. The integration and extent of hypertrophy strength training in in-season conditioning depend on the duration of the contest period, the frequency of the contests, and the proportion of the conditioning program. Based on the literature, 72 h between hypertrophy strength training and strength-power training should be provided to allow for adequate regeneration times and therefore maximal stimulus intensities in training. This conclusion is only valid if the muscle is not trained otherwise during this regeneration phase. Thus, rotating hypertrophy and strength-power sessions in a microcycle during the season is a viable option. Comparative studies in competitive athletes who integrated strength training during pre-season conditioning confirm a tendency for gains in explosive strength and statistically significant improvements in medicine ball throw through SPP but not through daily undulating periodization. These findings indicate that to maximize the speed-strength in the short term (peaking), elite athletes should perform strength-power training twice per week. It is possible to perform a single strength-power session with the method of maximum explosive strength actions moving high-weight loads (90% 1 repetition maximum [RM]) at least 1-2 days before competition because of the shorter regeneration times and potentiation effects. Compared with ballistic strength training (30% 1 RM), this method has been shown to provide statistically superior gains in maximal strength, peak power, impulse size, and explosive strength during tapering in track-and-field throwers. The speed-strength performance in drop jumps of strength-trained subjects showed potentiation effects 48-148 h after a single strength-power training session. Regarding neuromuscular performance, plyometric exercises can even be performed after strength-power training on the same day if a minimum rest period of 3 h is provided. PMID- 26133517 TI - Taking a PAWS to Reflect on How the Work of a Therapy Dog Supports a Trauma Informed Approach to Prisoner Health. AB - Canada's Correctional Investigator has found that mental health disorders, alone or in combination with alcohol and drug abuse, challenge public health and safety. Trauma is a key contributor among Canada's inmate population. Therapy dogs can assist in supporting individuals with mental health, addiction, and trauma concerns. This case report presents the work of a St. John Ambulance therapy dog in a trauma-informed approach to prisoner health. The Substance Abuse and Mental Health Services Administration articulates six evidence-based trauma principles for service providers; safety; trustworthiness and transparency; peer support; collaboration and mutuality; empowerment, voice, and choice; and cultural, historical, and gender issues. These principles are used as a lens to examine what the therapy dog appears to offer instinctively and effortlessly in its interactions with prisoners. Illustrative examples are provided.Video Abstract available for additional insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JFN/A16). PMID- 26133518 TI - Stranded Motorist Deaths in Harris County, Texas: A Deadly Game of Highway Roulette. AB - The Centers for Disease Control and Prevention recognize that nonintentional injuries are a leading cause of death and disability. Current literature identifies risk factors and prevention strategies for motor vehicle crashes and auto-pedestrian incidents. However, scant literature provides prevention strategies for the stranded motorist (SM). The SM is defined as any occupant of a vehicle that is stopped in or on the side of a road. The purpose of this case report was to identify and describe the circumstances of SM death. Death data were identified from the medicolegal death investigation agency. Between 2004 and 2014, Harris County, Texas, had 46 SM deaths, and of those deaths, 74% occurred while outside the vehicle, and most motorists become stranded because of mechanical issues (67%). An outcome of the report was a public service announcement aimed at primary injury prevention. The medicolegal death investigation agency changed how they categorize the SM. PMID- 26133519 TI - Adjuvant treatment with infusional 5-fluorouracil in high risk adenocarcinoma of the stomach or gastroesophageal junction. AB - PURPOSE: In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5 fluorouracil continuous infusion scheme. METHODS: We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m(2) iv with leucovorin 200 mg/m(2) iv and 1200 mg/m(2) in 46-hour infusion of 5-fluorouracil (D'Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5 fluorouracil continuously infusion 225 mg/m(2)/day and four additional infusions of chemotherapy one month after complete radiochemotherapy. RESULTS: Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3-102.1 months), and the 3-year survival rates were 52.7 %. CONCLUSIONS: This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results. PMID- 26133520 TI - GRP78 and alpha2-macroglobulin are new promising targets for metastatic castrate resistant prostate cancer treatment. PMID- 26133521 TI - Intraoperative electron-beam radiation therapy with or without external-beam radiotherapy in the management of paraaortic lymph-node oligometastases from gynecological malignancies. AB - PURPOSE: To analyze long-term outcomes and prognostic factors in patients with paraaortic lymph-node oligometastases (LNO) from gynecological malignancies treated in a multimodal protocol. METHODS: Patients with a histological diagnosis of LNO gynecological cancer [uterine cervix (n = 14, 40 %), endometrial (n = 18, 51 %), ovarian (n = 3, 9 %)] who underwent surgery with radical intent and intraoperative radiotherapy (IORT), median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 51 % received external-beam radiotherapy (EBRT). RESULTS: From 1997 to 2012, a total of 35 patients from a single institution were analyzed. With a median follow-up time of 55 months (range 2-148), 5-year loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS) were 79, 44 and 49 %, respectively. On multivariate analysis, no EBRT treatment to the LNO (p = 0.03), and time interval from primary tumor diagnosis to LNO <24 months (p = 0.04) remained significantly associated with locoregional recurrence (LRR). We found on multivariate analysis that only R1 margin status (p = 0.01) was significantly associated with OS. CONCLUSION: From the current series of patients with gynecological LNO, it emerges the fact that EBRT promotes local control. Future prospective studies might be designed according to the predicted risk of LRR focusing on different subgroups. PMID- 26133522 TI - Salivary gland myoepithelial carcinoma. AB - Salivary gland myoepithelial carcinoma (MC) or malignant myoepithelioma is a rare entity. MC usually presents as a slow-growing painless mass arising in the parotid gland, but may involve other salivary glands. This tumour may be particularly locally aggressive, but its clinical and biological features are not yet fully understood. MC may arise from pre-existing benign lesions, such as pleomorphic adenomas or benign myoepitheliomas, or may arise de novo. It usually affects patients over 50 years old, with no gender preference. Because it is often asymptomatic, the presentation and diagnosis can be delayed by months, even years. The current WHO classification considers MC to be an intermediate- to high grade malignancy. Other published data suggest it is likely to be a high-grade neoplasm, consistent with its aggressive behaviour. Its epidemiology, histopathological features, immunohistochemical profile, clinical behaviour and optimal management are not well understood. Following review of the current literature we aim to address these. PMID- 26133523 TI - [Cardiovascular diseases in childhood]. AB - Cardiac imaging in childhood poses significant challenges for the instrumentation and the operator. Small cardiac structures, high heart beat rates, non-compliant or sedated patients and in addition to the challenge of detecting acquired heart diseases, a broad spectrum of congenital heart defects (CHD) needs to be addressed, preferably without the burden of ionizing radiation. These challenges require not only accurate anatomical imaging but also a comprehensive assessment of hemodynamic and functional parameters for prognosis and risk stratification. With an incidence of 1 % among all live births, CHDs are the most frequent form of congenital organ dysplasia. Advances in the diagnostics and treatment of even very complex forms of CHD lead to a higher number of patients requiring follow-up with cardiac imaging in childhood. As an example congenital defects, such as tetralogy of Fallot or valvular regurgitation need regular assessment of cardiac volumes and function. Arrhythmogenic right ventricular cardiomyopathy requires recognition of fatty infiltration in the myocardium and in hypertrophic cardiomyopathy or myocarditis evidence of scar tissue or fibrosis portends a poor prognosis for the patient. For adequate assessment of the hemodynamics of complex CHD, the investigator must be aware of the patient's medical history in order to judge the course of the circulation that might diverge from the norm. A close knit cooperation and communication between all involved medical sub-specialties therefore needs to be guaranteed. PMID- 26133524 TI - Erratum to: Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in plants. PMID- 26133525 TI - Scientific Versus Experiential Evidence: Discourse Analysis of the Chronic Cerebrospinal Venous Insufficiency Debate in a Multiple Sclerosis Forum. AB - BACKGROUND: The vascular hypothesis of multiple sclerosis (MS), called chronic cerebrospinal venous insufficiency (CCSVI), and its treatment (known as liberation therapy) was immediately rejected by experts but enthusiastically gripped by patients who shared their experiences with other patients worldwide by use of social media, such as patient online forums. Contradictions between scientific information and lay experiences may be a source of distress for MS patients, but we do not know how patients perceive and deal with these contradictions. OBJECTIVE: We aimed to understand whether scientific and experiential knowledge were experienced as contradictory in MS patient online forums and, if so, how these contradictions were resolved and how patients tried to reconcile the CCSVI debate with their own illness history and experience. METHODS: By using critical discourse analysis, we studied CCSVI-related posts in the patient online forum of the German MS Society in a chronological order from the first post mentioning CCSVI to the time point when saturation was reached. For that time period, a total of 117 CCSVI-related threads containing 1907 posts were identified. We analyzed the interaction and communication practices of and between individuals, looked for the relation between concrete subtopics to identify more abstract discourse strands, and tried to reveal discourse positions explaining how users took part in the CCSVI discussion. RESULTS: There was an emotionally charged debate about CCSVI which could be generalized to 2 discourse strands: (1) the "downfall of the professional knowledge providers" and (2) the "rise of the nonprofessional treasure trove of experience." The discourse strands indicated that the discussion moved away from the question whether scientific or experiential knowledge had more evidentiary value. Rather, the question whom to trust (ie, scientists, fellow sufferers, or no one at all) was of fundamental significance. Four discourse positions could be identified by arranging them into the dimensions "trust in evidence-based knowledge," "trust in experience-based knowledge," and "subjectivity" (ie, the emotional character of contributions manifested by the use of popular rhetoric that seemed to mask a deep personal involvement). CONCLUSIONS: By critical discourse analysis of the CCSVI discussion in a patient online forum, we reconstruct a lay discourse about the evidentiary value of knowledge. We detected evidence criteria in this lay discourse that are different from those in the expert discourse. But we should be cautious to interpret this dissociation as a sign of an intellectual incapability to understand scientific evidence or a naive trust in experiential knowledge. Instead, it might be an indication of cognitive dissonance reduction to protect oneself against contradictory information. PMID- 26133526 TI - Visualization and dissemination of multidimensional proteomics data comparing protein abundance during Caenorhabditis elegans development. AB - Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/ . Graphical Abstract ?. PMID- 26133527 TI - Chemical ionization mass spectrometry using carbon nanotube field emission electron sources. AB - A novel chemical ionization (CI) source has been developed based on a carbon nanotube (CNT) field emission electron source. The CNT-based electron source was evaluated and compared with a standard filament thermionic electron source in a commercial explosives trace detection desktop mass spectrometer. This work demonstrates the first reported use of a CNT-based ion source capable of collecting CI mass spectra. Both positive and negative modes were investigated. Spectra were collected for a standard mass spectrometer calibration compound, perfluorotributylamine (PFTBA), as well as trace explosives including trinitrotoluene (TNT), Research Department explosive (RDX), and pentaerythritol tetranitrate (PETN). The electrical characteristics, lifetime at operating pressure, and power requirements of the CNT-based electron source are reported. The CNT field emission electron sources demonstrated an average lifetime of 320 h when operated in constant emission mode under elevated CI pressures. The ability of the CNT field emission source to cycle on and off can provide enhanced lifetime and reduced power consumption without sacrificing performance and detection capabilities. Graphical Abstract ?. PMID- 26133530 TI - Editor's Desk: The Value Issue. PMID- 26133531 TI - Exploring the Value Proposition for Workforce Health: Business Leader Attitudes About the Role of Health as a Driver of Productivity and Performance. AB - A survey of more than 500 leaders showing how business leaders think about the concepts of productivity and performance, and also their beliefs about the connection between health, productivity, and performance. PMID- 26133532 TI - What Really Does Matter in Workplace Wellness, and Who Cares About ROI Anyway? PMID- 26133534 TI - Persistent Sexual Dysfunction and Suicidal Ideation in Young Men Treated with Low Dose Finasteride: A Pharmacovigilance Study. AB - STUDY OBJECTIVE: Finasteride, a 5alpha-reductase inhibitor, is marketed in a low dose (1 mg) as a popular therapy for androgenic alopecia in young men. As case reports and small surveys have suggested a link between persistent sexual dysfunction (SD) and suicidal ideation (SI) with low-dose finasteride, the aim of this study was to detect signals of SD and SI secondary to low-dose finasteride use in young men. DESIGN: Retrospective pharmacovigilance disproportionality analysis. DATA SOURCE: United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. MEASUREMENTS AND MAIN RESULTS: Low-dose finasteride-related adverse event reports for men aged 18-45 years that were submitted to the FAERS between 1998 and 2013 were retrieved. Multi-item Gamma Poisson Shrinker disproportionality analysis was applied to calculate the empirical Bayes geometric mean (EBGM) and corresponding 95% confidence interval (CI) as an association metric between low-dose finasteride and the events of interest. Signals were defined as associations with thresholds of a CI lower limit of 2.0 or greater. Medical Dictionary for Regulatory Activities Preferred Terms denoting to SD and SI were identified to reflect the outcome of interest. In total, of 4910 reports, 577 persistent SD and 39 SI adverse event reports (11.8% and 7.9%, respectively) were identified for young men using low-dose finasteride; 34 (87.2%) of the 39 men with SI also experienced SD. The majority of these events were serious (e.g., contributed to the patient's death, hospitalization, or disability). Low-dose finasteride was associated with more than expected reporting of SD in young men compared with reporting of these events with all other drugs within the database (EBGM 28.0, 95% CI 26.1-30.0). Disproportional reporting in SI events was noted, although it did not reach signal threshold (EBGM 1.72; 95% CI 1.31-2.23). Among serious SD events, 43% led to disability; 28% required medical intervention, including hospitalization; and 5% were life-threatening. Six fatal SD reports were identified. CONCLUSION: Persistent SD might be a potential risk of low-dose finasteride for androgenic alopecia therapy in young men, and this risk might contribute to SI. Our findings provide a strong hypothesis for pharmacoepidemiologic studies to further examine this association. PMID- 26133535 TI - 150th Anniversary Series: Desmosomes and the Hallmarks of Cancer. AB - Desmosomes represent adhesive, spot-like intercellular junctions that in association with intermediate filaments mechanically link neighboring cells and stabilize tissue architecture. In addition to this structural function, desmosomes also act as signaling platforms involved in the regulation of cell proliferation, differentiation, migration, morphogenesis, and apoptosis. Thus, deregulation of desmosomal proteins has to be considered to contribute to tumorigenesis. Proteolytic fragmentation and downregulation of desmosomal cadherins and plaque proteins by transcriptional or epigenetic mechanisms were observed in different cancer entities suggesting a tumor-suppressive role. However, discrepant data in the literature indicate that context-dependent differences based on alternative intracellular, signal transduction lead to altered outcome. Here, modulation of Wnt/beta-catenin signaling by plakoglobin or desmoplakin and of epidermal growth factor receptor signaling appears to be of special relevance. This review summarizes current evidence on how desmosomal proteins participate in carcinogenesis, and depicts the molecular mechanisms involved. PMID- 26133536 TI - Antioxidant and antimicrobial activity of natural phenolic extract from defatted soybean flour by-product for stone fruit postharvest application. AB - BACKGROUND: Fresh fruit is highly perishable during storage and transport, so there has been growing interest in finding safe and natural antimicrobial compounds as a control tool. Phenolic compounds are secondary metabolites naturally present in vegetable material and have been associated with antimicrobial and antioxidant properties. Therefore, the aim of this study was to investigate the antioxidant capacity and potential antimicrobial effect of phenolic extract obtained from defatted soybean flour against selected pathogenic bacteria and microorganisms responsible of fruit decay. RESULTS: Analysis of phenolic composition by HPLC-MS showed the presence of a wide range of compounds, with isoflavones and phenolic acids the main polyphenols identified. Furthermore, the phenolic extract had important antioxidant activity by two different assays. Related to antimicrobial activity, in vitro experiments demonstrated that phenolic extract displayed a high activity against the main foodborne pathogens, while a moderate inhibition was found against five spoilage yeasts and Monilia laxa and a scarce effect for Penicillium glabrum, Cladosporium uredinicola and Botrytis cinerea. Interestingly these compounds considerably inhibited the mycelial growth of Monilia laxa, in both in vitro and in vivo experiments. CONCLUSION: The results of the present study revealed that defatted soybean flour is an important source of phenolic compounds with remarkable antimicrobial and antioxidant activity, suggesting the possibility of using them as natural additives in postharvest treatments to extend the shelf life of fruit. PMID- 26133537 TI - New finding that might explain why the skin wrinkles more on various parts of the face. AB - The mechanism of formation of facial wrinkles has not been fully clarified due to the existence of many distinct influential factors. To clarify the relationship between facial wrinkles and structures in the skin, especially sebaceous glands, image analysis was performed on the forehead and lateral canthus regions of cadaveric skin specimens; 58 male and female donated cadavers (age range at death 20s - 90 s) were included in the study. Specimens were obtained from forehead and lateral canthus region after measuring wrinkle depth. Then tissue slices were prepared to observe the sebaceous gland and its density was measured and analyzed in relation to wrinkle depth, retinacula cutis density, dermal thickness, and solar elastosis degree. A correlation was found between sebaceous gland density and wrinkle depth in forehead specimens with a lower retinacula cutis density. Wrinkles were shallower in specimens with a higher sebaceous gland density. However, no such correlation was found in lateral canthus wrinkles, presumably due to the lack of sebaceous glands in that region. In addition, specimens with a higher sebaceous gland density tended to have a thicker dermis and/or less solar elastosis. Sebaceous gland density seems to be one of the multiple factors that prevent wrinkle deepening, and that is why wrinkles are deeper in the lateral canthus area than in the forehead. Functional studies will elucidate the mechanism of wrinkle formation in the future. PMID- 26133538 TI - Does oral alpha-galactosidase relieve irritable bowel symptoms? AB - OBJECTIVE: Abdominal bloating is reported by a majority of irritable bowel syndrome (IBS) patients. Excess colonic fermentation may cause gaseous symptoms. Several foodstuffs contain oligosaccharides with an alpha-galactosidic linkage that is resistant to mammalian hydrolases. Assisted hydrolysis by exogenous alpha galactosidase enzyme (AG) could offer a way of controlling IBS symptoms by reducing colonic fermentation and gas production. The aim of this study was to assess the effect of AG on symptom severity and quality of life in IBS patients with abdominal bloating or flatulence. METHODS: A total of 125 subjects with IBS received AG or placebo at meals for 12 weeks. IBS-Symptom Severity Score (IBS SSS) and quality of life (QoL) were assessed at baseline, during the treatment and at 4-week follow-up. RESULTS: AG showed a trend toward a more prominent decrease in IBS-SSS. The responder rate at week 16 was higher for the AG group. No difference was detected in QoL between AG and placebo groups. A total of 25 patients (18 in AG group and 7 in placebo group, p = 0.016) withdrew from the study. Abdominal pain and diarrhea were more often reported as reason for withdrawal in AG group. CONCLUSIONS: We found no evidence to support the use of AG routinely in IBS patients. Improvement of clinical response at 4-week follow up may suggest a long-term effect of unknown mechanism, but could also be attributed to non-responder drop out. Gastrointestinal (GI) side effects may be a coincidence in this study, but irritation of GI tract by AG administration cannot be excluded. PMID- 26133539 TI - Photothermal confocal multicolor microscopy of nanoparticles and nanodrugs in live cells. AB - Growing biomedical applications of non-fluorescent nanoparticles (NPs) for molecular imaging, disease diagnosis, drug delivery, and theranostics require new tools for real-time detection of nanomaterials, drug nano-carriers, and NP-drug conjugates (nanodrugs) in complex biological environments without additional labeling. Photothermal (PT) microscopy (PTM) has enormous potential for absorption-based identification and quantification of non-fluorescent molecules and NPs at a single molecule and 1.4 nm gold NP level. Recently, we have developed confocal PTM providing three-dimensional (3D) mapping and spectral identification of multiple chromophores and fluorophores in live cells. Here, we summarize recent advances in the application of confocal multicolor PTM for 3D visualization of single and clustered NPs, alone and in individual cells. In particular, we demonstrate identification of functionalized magnetic and gold silver NPs, as well as graphene and carbon nanotubes in cancer cells and among blood cells. The potential to use PTM for super-resolution imaging (down to 50 nm), real-time NP tracking, guidance of PT nanotherapy, and multiplex cancer markers targeting, as well as analysis of non-linear PT phenomena and amplification of nanodrug efficacy through NP clustering and nano-bubble formation are also discussed. PMID- 26133540 TI - HIV Drug Resistance Surveillance Among Jamaican Men Who Have Sex with Men Should Be Prioritized for Reducing HIV Transmission. AB - The prevalence of human immunodeficiency virus type 1 (HIV-1) is highest among men who have sex with men (MSM) in Jamaica but no genotypic data are available on the virus strains that are responsible for the epidemic among this key population. HIV-1 polymerase (pol) genes from 65 MSM were sequenced and used to predict drug resistance mutations. An HIV drug resistance prevalence of 28% (minimum 13%) was observed among this cohort, with the most frequent mutations conferring resistance to efavirenz, nevirapine, and lamivudine. Phylogenetic analysis of the sequences revealed 10 times the number of linked HIV infections among this cohort than respondent reporting. HIV treatment and prevention efforts in Jamaica could benefit significantly from Pol genotyping of the HIV strains infecting socially vulnerable MSM prior to initiating antiretroviral therapy (ART), as this would guide suppressive ART and unearth HIV transmission clusters to enable more effective delivery of treatment and prevention programs. PMID- 26133541 TI - The effects of some bromophenols on human carbonic anhydrase isoenzymes. AB - Carbonic anhydrases (CAs, EC 4.2.1.1), which are involved in a variety of physiological and pathological processes, are ubiquitous metalloenzymes mainly catalyzing the reversible hydration of carbon dioxide (CO2) to bicarbonate ([Formula: see text]) and proton (H(+)). In this study, a dozen of bromophenol derivatives (1-12) were evaluated as metalloenzyme CA (EC 4.2.1.1) inhibitors against the human carbonic anhydrase isoenzymes I and II (hCA I and II). Cytosolic hCA I and II isoenzymes were effectively inhibited by bromophenol derivatives (1-12) with Kis in the low nanomolar range of 1.85 +/- 0.58 to 5.04 +/- 1.46 nM against hCA I and in the range of 2.01 +/- 0.52 to 2.94 +/- 1.31 nM against hCA II, respectively. PMID- 26133543 TI - Facile and Scalable Preparation of Solid Silver Nanoparticles (<10 nm) for Flexible Electronics. AB - Metal conductive ink for flexible electroncs has exhibited a promising future recently. Here, an innovative strategy was reported to synthesize silver nanocolloid (2.5+/-0.5 nm) and separate solid silver nanoparticles (<10 nm) effectively. Specifically, silver nitrate (AgNO3) was used as a silver precursor, sodium borohydride (NaBH4) as a reducing agent, fatty acid (CnH2n+1COOH) as a dispersant agent, and ammonia (NH3.H2O) and hydrochloride (HCl) as a pH regulator and complexing agent in aqueous solution. The main mechanism is the solubility changes of fatty acid salts (CnH2n+1COO-NH4+) and fatty acid (CnH2n+1COOH) coated on the synthesized silver nanoparticles (NPs) in aqueous solution. This change determines the suspension and precipitation of silver NPs directly. The results show that when n in dispersant is 12 and molar ratio (C12H24O2/AgNO3) is 1.0, the separation yield of silver NPs is up to 94.8%. After sintering at 125 degrees C for 20 min, the as-prepared conductive silver nanoink (20 wt %) presents a satisfactory resistivity (as low as 6.6 MUOmega.cm on the polyester-PET substrate), about 4 times the bulk silver. In addition, the efficacy of the as prepared conductive ink was verified with the construction of a radio frequency antenna by inkjet printing and conductive character pattern (Fudan-Fudan) by direct wiring, showing excellent electrical performance. PMID- 26133542 TI - Cyclopropane derivatives as potential human serine racemase inhibitors: unveiling novel insights into a difficult target. AB - d-Serine is the co-agonist of NMDA receptors and binds to the so-called glycine site. d-Serine is synthesized by human serine racemase (SR). Over activation of NMDA receptors is involved in many neurodegenerative diseases and, therefore, the inhibition of SR might represent a novel strategy for the treatment of these pathologies. SR is a very difficult target, with only few compounds so far identified exhibiting weak inhibitory activity. This study was aimed at the identification of novel SR inhibitor by mimicking malonic acid, the best-known SR inhibitor, with a cyclopropane scaffold. We developed, synthesized, and tested a series of cyclopropane dicarboxylic acid derivatives, complementing the synthetic effort with molecular docking. We identified few compounds that bind SR in high micromolar range with a lack of significant correlation between experimental and predicted binding affinities. The thorough analysis of the results can be exploited for the development of more potent SR inhibitors. PMID- 26133544 TI - pH-Responsive Micelle Sequestrant Polymers Inhibit Fat Absorption. AB - Current antiobesity therapeutics are associated with side effects and/or poor long-term patient compliance, necessitating development of more efficacious and safer alternatives. Herein, we designed and engineered a new class of orally acting pharmaceutical agents, or micelle sequestrant polymers (MSPs), that could respond to the pH change in the gastrointestinal (GI) tract and potentially sequester lipid micelles; inhibiting lipid absorption through a pH-triggered flocculation process. These MSPs, derived from poly(2-(diisopropylamino)ethyl methacrylate) and poly(2-(dibutylamino)ethyl methacrylate), were soluble in acidic media, but they transitioned to become insoluble around pH 7.2 and 6.1, respectively. MSPs showed substantial bile acid and triglyceride sequestration capacity with fast pH response tested in vitro. In vivo study showed that orally dosed MSPs significantly enhanced fecal elimination of triglycerides and bile acids. Several MSPs increased fecal elimination of triglycerides by 9-10 times compared with that of the control. In contrast, fecal concentration of bile acids, but not triglycerides, was increased by cholestyramine or Welchol. Importantly, fecal elimination of bile acids and triglycerides was unaltered by addition of control dietary fibers. MSPs may serve as a novel approach to weight loss that inhibits excess caloric intake by preventing absorption of excess dietary triglycerides. PMID- 26133545 TI - Demographic factors and dental health of Swedish children and adolescents. AB - OBJECTIVE: To investigate the dental health of Swedish children and adolescents with reference to age, gender and residence. MATERIAL AND METHODS: Electronic dental records from 300,988 3-19-year-olds in one Swedish region were derived in a cross-sectional study in years 2007-2009. The DMFT system was used. Age was categorized into 3-6/7-9/10-12/13-15/16-17/18-19-year-olds and residence into 'metropolitan', 'urban' and 'rural' areas. ANOVA, generalized linear regression models and Fisher's exact test were used. RESULTS: Among 7-9-year-old children, nine out of 10 were free from fillings and manifest caries, while for 18-19-year olds; this proportion was one third. Girls (18-19-year-olds) had a significantly lower risk of caries compared to boys of the same age, RR for the DT index = 0.83 (95% CI = 0.81-0.85). This pattern was reversed in 7-12-year-old children. Children and adolescents in metropolitan and urban areas had significantly more caries than subjects in rural areas, for instance the RR for the DT index in metropolitan 7-9-year-olds was 2.26 (95% CI = 2.11-2.42) compared to their rural counterparts. CONCLUSIONS: In the permanent dentition, the overall pattern revealed that girls <= 12 years had a higher risk of caries, while adolescent girls had a lower risk of caries, both compared with boys of corresponding ages. Living in an urban or metropolitan area entailed a higher risk of caries than living in a rural area. A greater occurrence of dental caries in adolescents than in children was confirmed. The findings should have implications for planning and evaluation of oral health promotion and disease prevention activities. PMID- 26133546 TI - Identification of novel monocistronic HTLV-1 mRNAs encoding functional Rex isoforms. AB - BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) gene expression is controlled by the key regulatory proteins Tax and Rex. The concerted action of these proteins results in a two-phase kinetics of viral expression that depends on a time delay between their action. However, it is difficult to explain this delay, as Tax and Rex are produced from the same mRNA. In the present study we investigated whether HTLV-1 may produce novel mRNA species capable of expressing Rex and Tax independently. FINDINGS: Results revealed the expression of three alternatively spliced transcripts coding for novel Rex isoforms in infected cell lines and in primary samples from infected patients. One mRNA coded for a Tax isoform and a Rex isoform, and two mRNAs coded for Rex isoforms but not Tax. Functional assays showed that these Rex isoforms exhibit activity comparable to canonic Rex. An analysis of the temporal expression of these transcripts upon ex vivo culture of cells from infected patients and cell lines transfected with a molecular clone of HTLV-1 revealed early expression of the dicistronic tax/rex mRNAs followed by the monocistronic mRNAs coding for Rex isoforms. CONCLUSION: The production of monocistronic HTLV-1 mRNAs encoding Rex isoforms with comparable activity to canonical Rex, but with distinct timing, would support a prolonged duration of Rex function with gradual loss of Tax, and is consistent with the two-phase expression kinetics. A thorough understanding of these regulatory circuits will shed light on the basis of viral latency and provide groundwork to develop strategies for eradicating persistent infections. PMID- 26133547 TI - Unmet clinical needs in chronic migraine: Rationale for study and design of COMPEL, an open-label, multicenter study of the long-term efficacy, safety, and tolerability of onabotulinumtoxinA for headache prophylaxis in adults with chronic migraine. AB - BACKGROUND: Chronic migraine is a neurological condition with a large individual and socioeconomic burden of disease. The recently completed Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical development program established the efficacy and safety of onabotulinumtoxinA as a prophylactic treatment for chronic migraine patients. However, clinical questions remain. A long-term evaluation study of onabotulinumtoxinA aims to address some of the remaining questions in the treatment of chronic migraine. The clinical rationale, study design, and treatment plan of this ongoing study are reviewed in this paper. METHODS/DESIGN: The Chronic migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) study will enroll approximately 500 adult patients with chronic migraine at international sites. Patients will be evaluated over 108 weeks, following a 4-week baseline period. Qualified subjects will receive 155 U of onabotulinumtoxinA every 12 weeks for 9 open-label cycles. The primary endpoint will be mean change from baseline in frequency of headache days at 108 weeks. Other endpoints will include additional assessments of the efficacy and safety of onabotulinumtoxinA and the effect of onabotulinumtoxinA on quality-of life measures, disability, and health economic outcomes. The impact of onabotulinumtoxinA on common comorbidities (eg, sleep, anxiety, and fatigue) will also be assessed. DISCUSSION: Recruitment and enrollment are ongoing. Post approval, open-label studies are often designed to more closely resemble clinical practice and provide an opportunity to continue the evaluation of the efficacy and safety of approved treatments. By creating a large database and analyzing a variety of outcome measures over an extended time frame, the COMPEL study will seek to contribute substantially to the existing knowledge of the chronic migraine population and the long-term management of this debilitating disorder. CLINICAL TRIAL REGISTRATION NUMBER: NCT01516892. PMID- 26133548 TI - Smoking cessation and smokefree environments for tuberculosis patients in Indonesia-a cohort study. AB - BACKGROUND: Research indicates that smoking substantially increases the risk of tuberculosis (TB), delay in diagnosis, failure of TB treatment and death from TB. Quitting smoking is one of the best ways to prevent unwanted outcomes. Exposure to secondhand smoke increases the risks of both TB infection and development of active TB disease among children and adults. TB patients who smoke in the home are also placing their families at a greater risk of TB infection. It is very important to keep homes smokefree. The present study assessed the implementation and effectiveness of an intervention that promotes smoking cessation and smokefree environments for TB patients. METHODS: All consecutive new sputum smear positive TB patients (aged >= 15 years old) diagnosed and registered in 17 health centres between 1 January 2011 and 31 December 2012 were enrolled. The ABC (A=ask, B=brief advice, C=cessation support) intervention was offered for 5 to 10 minutes within DOTS services at each visit. Smoking status and smokefree environments at home were assessed at the first visit, each monthly follow up and at month six. Factors associated with quitting were analysed by univariable and multivariable analysis RESULTS: Of the 750 TB patients registered, 582 (77.6%) were current smokers, 40 (5.3%) were ex-smokers and 128 (17.1%) were never smokers. Of the 582 current smokers, 66.8% had quit smoking at month six. A time from waking to first cigarette of >30 minutes, having a smokefree home and the display of "no smoking" signage at home at month six were significantly associated with quitting. Of the 750 TB patients, 86.1% had created a smokefree home at six month follow-up compared with 18.5% at baseline. All 80 health facilities were 100% tobacco-free at the end of 2012 compared with only 52 (65%) when the intervention began in March 2011. CONCLUSIONS: Brief advice of 5-10 minutes with minimal cessation support at every visit of TB patients resulted in high quit rates and higher awareness of adverse health effects of secondhand smoke exposure, which led patients to make their homes smokefree and health providers to make health care tobacco-free. PMID- 26133549 TI - Nitric Oxide Increases Arterial Endotheial Permeability through Mediating VE Cadherin Expression during Arteriogenesis. AB - Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis. PMID- 26133550 TI - Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity. AB - Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-beta type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID- 26133551 TI - HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days--Implications for HIV Remission. AB - HIV infection can be effectively controlled by anti-retroviral therapy (ART) in most patients. However therapy must be continued for life, because interruption of ART leads to rapid recrudescence of infection from long-lived latently infected cells. A number of approaches are currently being developed to 'purge' the reservoir of latently infected cells in order to either eliminate infection completely, or significantly delay the time to viral recrudescence after therapy interruption. A fundamental question in HIV research is how frequently the virus reactivates from latency, and thus how much the reservoir might need to be reduced to produce a prolonged antiretroviral-free HIV remission. Here we provide the first direct estimates of the frequency of viral recrudescence after ART interruption, combining data from four independent cohorts of patients undergoing treatment interruption, comprising 100 patients in total. We estimate that viral replication is initiated on average once every ~6 days (range 5.1- 7.6 days). This rate is around 24 times lower than previous thought, and is very similar across the cohorts. In addition, we analyse data on the ratios of different 'reactivation founder' viruses in a separate cohort of patients undergoing ART interruption, and estimate the frequency of successful reactivation to be once every 3.6 days. This suggests that a reduction in the reservoir size of around 50 70-fold would be required to increase the average time-to-recrudescence to about one year, and thus achieve at least a short period of anti-retroviral free HIV remission. Our analyses suggests that time-to-recrudescence studies will need to be large in order to detect modest changes in the reservoir, and that macaque models of SIV latency may have much higher frequencies of viral recrudescence after ART interruption than seen in human HIV infection. Understanding the mean frequency of recrudescence from latency is an important first step in approaches to prolong antiretroviral-free viral remission in HIV. PMID- 26133552 TI - Do Children and Adolescents with Anorexia Nervosa Display an Inefficient Cognitive Processing Style? AB - OBJECTIVE: This study aimed to examine neuropsychological processing in children and adolescents with Anorexia Nervosa (AN). The relationship of clinical and demographic variables to neuropsychological functioning within the AN group was also explored. METHOD: The performance of 41 children and adolescents with a diagnosis of AN were compared to 43 healthy control (HC) participants on a number of neuropsychological measures. RESULTS: There were no differences in IQ between AN and HC groups. However, children and adolescents with AN displayed significantly more perseverative errors on the Wisconsin Card Sorting Test, and lower Style and Central Coherence scores on the Rey Osterrieth Complex Figure Test relative to HCs. CONCLUSION: Inefficient cognitive processing in the AN group was independent of clinical and demographic variables, suggesting it might represent an underlying trait for AN. The implications of these findings are discussed. PMID- 26133554 TI - Investigation of Marine-Derived Fungal Diversity and Their Exploitable Biological Activities. AB - Marine fungi are potential producers of bioactive compounds that may have pharmacological and medicinal applications. Fungi were cultured from marine brown algae and identified using multiple target genes to confirm phylogenetic placement. These target genes included the internal transcribed spacer (ITS), the nuclear large subunit (LSU), and the beta-tubulin region. Various biological activities of marine-derived fungi were evaluated, including their antifungal, antioxidant and cellulolytic enzyme activities. As a result, a total of 50 fungi was isolated from the brown algae Sargassum sp. Among the 50 isolated fungi, Corollospora angusta was the dominant species in this study. The genus Arthrinium showed a relatively strong antifungal activity to all of the target plant pathogenic fungi. In particular, Arthrinium saccharicola KUC21221 showed high radical scavenging activity and the highest activities in terms of filter paper units (0.39 U/mL), endoglucanase activity (0.38 U/mL), and beta-glucosidase activity (1.04 U/mL). PMID- 26133555 TI - Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion. AB - Critical limb ischemia (CLI) induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate. Monocytes negatively isolated with magnetic beads from peripheral blood of healthy donors were treated with fucoidan. Fucoidan induced a 1.5-fold increase in monocyte adhesion to gelatin (p < 0.05) and a five-fold increase in chemotaxis in Boyden chambers (p < 0.05). Fucoidan also enhanced migration 2.5-fold in a transmigration assay (p < 0.05). MMP9 activity in monocyte supernatants was significantly enhanced by fucoidan (p < 0.05). Finally, Western blot analysis of fucoidan-treated monocytes showed upregulation of ERK/p38 phosphorylation. Inhibition of ERK/p38 phosphorylation abrogated fucoidan enhancement of migration (p < 0.01). Fucoidan displays striking biological effects, notably promoting monocyte adhesion and migration. These effects involve the ERK and p38 pathways, and increased MMP9 activity. Fucoidan could improve critical limb ischemia by promoting monocyte recruitment. PMID- 26133553 TI - Biological Activity of Recently Discovered Halogenated Marine Natural Products. AB - This review presents the biological activity-antibacterial, antifungal, anti parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity-of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included. PMID- 26133556 TI - A Cost-Effectiveness Analysis of First Trimester Non-Invasive Prenatal Screening for Fetal Trisomies in the United States. AB - BACKGROUND: Non-invasive prenatal testing (NIPT) is a relatively new technology for diagnosis of fetal aneuploidies. NIPT is more accurate than conventional maternal serum screening (MSS) but is also more costly. Contingent NIPT may provide a cost-effective alternative to universal NIPT screening. Contingent screening used a two-stage process in which risk is assessed by MSS in the first stage and, based on a risk cutoff, high-risk pregnancies are referred for NIPT. The objective of this study was to (1) determine the optimum MSS risk cutoff for contingent NIPT and (2) compare the cost effectiveness of optimized contingent NIPT to universal NIPT and conventional MSS. STUDY DESIGN: Decision-analytic model using micro-simulation and probabilistic sensitivity analysis. We evaluated cost effectiveness from three perspectives: societal, governmental, and payer. RESULTS: From a societal perspective, universal NIPT dominated both contingent NIPT and MSS. From a government and payer perspective, contingent NIPT dominated MSS. Compared to contingent NIPT, adopting a universal NIPT would cost $203,088 for each additional case detected from a government perspective and $263,922 for each additional case detected from a payer perspective. CONCLUSIONS: From a societal perspective, universal NIPT is a cost-effective alternative to MSS and contingent NIPT. When viewed from narrower perspectives, contingent NIPT is less costly than universal NIPT and provides a cost-effective alternative to MSS. PMID- 26133557 TI - Identification of an Endophytic Antifungal Bacterial Strain Isolated from the Rubber Tree and Its Application in the Biological Control of Banana Fusarium Wilt. AB - Banana Fusarium wilt (also known as Panama disease) is one of the most disastrous plant diseases. Effective control methods are still under exploring. The endophytic bacterial strain ITBB B5-1 was isolated from the rubber tree, and identified as Serratia marcescens by morphological, biochemical, and phylogenetic analyses. This strain exhibited a high potential for biological control against the banana Fusarium disease. Visual agar plate assay showed that ITBB B5-1 restricted the mycelial growth of the pathogenic fungus Fusarium oxysporum f. sp. cubense race 4 (FOC4). Microscopic observation revealed that the cell wall of the FOC4 mycelium close to the co-cultured bacterium was partially decomposed, and the conidial formation was prohibited. The inhibition ratio of the culture fluid of ITBB B5-1 against the pathogenic fungus was 95.4% as estimated by tip culture assay. Chitinase and glucanase activity was detected in the culture fluid, and the highest activity was obtained at Day 2 and Day 3 of incubation for chitinase and glucanase, respectively. The filtrated cell-free culture fluid degraded the cell wall of FOC4 mycelium. These results indicated that chitinase and glucanase were involved in the antifungal mechanism of ITBB B5-1. The potted banana plants that were inoculated with ITBB B5-1 before infection with FOC4 showed 78.7% reduction in the disease severity index in the green house experiments. In the field trials, ITBB B5-1 showed a control effect of approximately 70.0% against the disease. Therefore, the endophytic bacterial strain ITBB B5-1 could be applied in the biological control of banana Fusarium wilt. PMID- 26133559 TI - Exploring heterogeneity among mentally disordered offenders--The key to targeting Interventions. PMID- 26133558 TI - Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (Review). AB - For early detection of cancer, education and screening are important, but the most critical factor is the development of early diagnostic tools. Methods that recognize the warning signs of cancer and take prompt action lead to an early diagnosis; simple tests can identify individuals in a healthy population who have the disease but have not developed symptoms. Early detection of cancer is significant and is one of the most promising approaches by which to reduce the growing cancer burden and guide curative treatment. The early diagnosis of patients with breast cancer is challenging, since it is the most common cancer in women worldwide. Despite the advent of mammography in screening for breast cancer, low-resource, low-cost alternative tools must be implemented to complement mammography findings. IgM is part of the first line of defense of an organism and is responsible for recognizing and eliminating infectious particles and removing transformed cells. Most studies on breast cancer have focused on the development of IgG-like molecules as biomarkers or as a treatment for the advanced stages of cancer, but autoantibodies (IgM) and tumor-associated antigens (proteins or carbohydrates with aberrant structures) have not been examined as early diagnostic tools for breast cancer. The present review summarizes the function of natural and adaptive IgM in eliminating cancer cells in the early stages of pathology and their value as early diagnostic tools. IgM, as a component of the immune system, is being used to identify tumor-associated antigens and tumor-associated carbohydrate antigens. PMID- 26133561 TI - Triamcinolone spray: no-rub application as effective as rub application. AB - BACKGROUND: Adherence to therapy is important to achieve successful treatment outcomes. Although effective, topical treatments in dermatology may result in sticky skin or may be too time-consuming to apply, thereby creating adherence issues. Spray formulations have excellent products aesthetics, but may require a 2-step application process. AIMS: This study was conducted to determine whether the spray formulation of triamcinolone acetonide (TAC) 0.2% works equally well in a no-rub and rub application process. METHODS: Fifty patients 18 years of age and older with mild symmetrical arm or leg eczema or atopic dermatitis were enrolled in a 2-week investigator-blinded study. One limb was randomized to be treated with TAC spray and no rubbing, and the other was to be treated with TAC spray and rubbing. Patients applied the spray three times daily for 2 weeks. The use of moisturizers was not permitted. RESULTS: After 2 weeks, there was a highly clinical and statistical (P < 0.001) improvement in all investigator and patient parameters evaluated with both the no-rub and rub techniques. There was no difference in final assessment scores between the no-rub and rub applications (P > 0.7), and no study product tolerability issues were identified. Transepidermal water loss and corneometry measures revealed no issues in skin barrier impairment even though patients were not permitted to use moisturizers. CONCLUSION: This study demonstrates the application parity between a no-rub and rub application of TAC spray in the absence of a moisturizer. Both techniques resulted in clinical and significant improvement in eczema and atopic dermatitis and neither resulted in skin barrier issues. PMID- 26133560 TI - Clinical Utility of a Coronary Heart Disease Risk Prediction Gene Score in UK Healthy Middle Aged Men and in the Pakistani Population. AB - BACKGROUND: Numerous risk prediction algorithms based on conventional risk factors for Coronary Heart Disease (CHD) are available but provide only modest discrimination. The inclusion of genetic information may improve clinical utility. METHODS: We tested the use of two gene scores (GS) in the prospective second Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284 cases), and Pakistani case-control studies from Islamabad/Rawalpindi (321 cases/228 controls) and Lahore (414 cases/219 controls). The 19-SNP GS included SNPs in loci identified by GWAS and candidate gene studies, while the 13-SNP GS only included SNPs in loci identified by the CARDIoGRAMplusC4D consortium. RESULTS: In NPHSII, the mean of both gene scores was higher in those who went on to develop CHD over 13.5 years of follow-up (19-SNP p=0.01, 13-SNP p=7x10-3). In combination with the Framingham algorithm the GSs appeared to show improvement in discrimination (increase in area under the ROC curve, 19-SNP p=0.48, 13-SNP p=0.82) and risk classification (net reclassification improvement (NRI), 19-SNP p=0.28, 13-SNP p=0.42) compared to the Framingham algorithm alone, but these were not statistically significant. When considering only individuals who moved up a risk category with inclusion of the GS, the improvement in risk classification was statistically significant (19-SNP p=0.01, 13-SNP p=0.04). In the Pakistani samples, risk allele frequencies were significantly lower compared to NPHSII for 13/19 SNPs. In the Islamabad study, the mean gene score was higher in cases than controls only for the 13-SNP GS (2.24 v 2.34, p=0.04). There was no association with CHD and either score in the Lahore study. CONCLUSION: The performance of both GSs showed potential clinical utility in European men but much less utility in subjects from Pakistan, suggesting that a different set of risk loci or SNPs may be required for risk prediction in the South Asian population. PMID- 26133562 TI - Re: Shear Wave Elastography for Localization of Prostate Cancer Lesions and Assessment of Elasticity Thresholds: Implications for Targeted Biopsies and Active Surveillance Protocols: K. Boehm, G. Salomon, B. Beyer, J. Schiffmann, K. Simonis, M. Graefen and L. Budaeus J Urol 2015;193:794-800. PMID- 26133565 TI - CORRIGENDUM: CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy. PMID- 26133566 TI - Phase 1 study assessing the steady-state concentration of ceftazidime and avibactam in plasma and epithelial lining fluid following two dosing regimens. AB - OBJECTIVES: The aim of this Phase 1, open-label study (NCT01395420) was to measure and compare concentrations of ceftazidime and avibactam in bronchial epithelial lining fluid (ELF) and plasma, following administration of two different dosing regimens in healthy subjects. PATIENTS AND METHODS: Healthy volunteers received 2000 mg of ceftazidime + 500 mg of avibactam (n = 22) or 3000 mg of ceftazidime + 1000 mg of avibactam (n = 21), administered intravenously every 8 h for 3 days (total of nine doses). Bronchoscopy with bronchoalveolar lavage was performed once per subject, 2, 4, 6 or 8 h after the last infusion. Pharmacokinetic parameters were estimated from individual plasma concentrations and the composite ELF concentration-time profile. Safety was assessed. RESULTS: Forty-three subjects received treatment (2000 mg of ceftazidime + 500 mg of avibactam, n = 22; 3000 mg of ceftazidime + 1000 mg of avibactam, n = 21). Plasma and ELF concentrations increased dose-proportionally for both drugs, with 1.5- and 2-fold increases in AUCtau, for respective components. Ceftazidime Cmax and AUCtau in ELF were ~ 23%-26% and 31%-32% of plasma exposure. Avibactam Cmax and AUCtau in ELF were ~ 28%-35% and 32%-35% of plasma exposure. ELF and plasma elimination were similar for both drugs. No serious adverse events were observed. CONCLUSIONS: Both ceftazidime and avibactam penetrated dose-proportionally into ELF, with ELF exposure to both drugs ~ 30% of plasma exposure. PMID- 26133567 TI - K-edge imaging with the XPAD3 hybrid pixel detector, direct comparison of CdTe and Si sensors. AB - We investigate the improvement from the use of high-Z CdTe sensors for pre clinical K-edge imaging with the hybrid pixel detectors XPAD3. We compare XPAD3 chips bump bonded to Si or CdTe sensors in identical experimental conditions. Image performance for narrow energy bin acquisitions and contrast-to-noise ratios of K-edge images are presented and compared. CdTe sensors achieve signal-to-noise ratios at least three times higher than Si sensors within narrow energy bins, thanks to their much higher detection efficiency. Nevertheless Si sensors provide better contrast-to-noise ratios in K-edge imaging when working at equivalent counting statistics, due to their better estimation of the attenuation coefficient of the contrast agent. Results are compared to simulated data in the case of the XPAD3/Si detector. Good agreement is observed when including charge sharing between pixels, which have a strong impact on contrast-to-noise ratios in K-edge images. PMID- 26133568 TI - Using Record Linkage to Improve Race Data Quality for American Indians and Alaska Natives in Two Pacific Northwest State Hospital Discharge Databases. AB - OBJECTIVE: To evaluate and adjust for American Indian and Alaska Native (AI/AN) racial misclassification in two hospital discharge datasets in the Pacific Northwest. DATA SOURCES/STUDY SETTING: Oregon (2010-2011) and Washington (2011) hospital discharge datasets were linked with the Northwest Tribal Registry (NTR), a registry of AI/AN individuals who accessed services at Indian health facilities in the Northwest. STUDY DESIGN: Record linkage was used to match state hospital records to the NTR. A state record was considered misclassified if it matched the NTR and was coded as non-AI/AN or missing race data. Effect of misclassification was evaluated by comparing prelinkage and postlinkage, age-adjusted hospital discharge rates. DATA COLLECTION/EXTRACTION METHODS: Researchers used Link Plus 2.0 software (Atlanta, GA, USA) for linkages and SAS 9.4 (Cary, NC, USA) for statistical analyses. PRINCIPAL FINDINGS: In Oregon, 55.4 percent of matching records were misclassified (66.5 percent miscoded white, and 22.1 percent were missing race information). In Washington, 44.9 percent of matching records were misclassified (61.8 percent miscoded white, and 32.7 percent were missing race information). Linkage increased ascertainment of AI/AN hospitalizations by 31.8 percent in Oregon and 33.9 percent in Washington. Linkage increased the rate ratio (RR) for AI/AN hospitalizations in comparison to non-Hispanic whites (NHW) from 0.81 to 1.07 in Oregon, and from 1.21 to 1.62 in Washington. CONCLUSION: Correction of race in hospital discharge datasets through linkage with a reference file of known AI/AN individuals is an important first step before analytic research on AI/AN health care in the Pacific Northwest can be accomplished with administrative datasets. PMID- 26133569 TI - Membrane-Associated Conformation of HIV-1 Nef Investigated with Hydrogen Exchange Mass Spectrometry at a Langmuir Monolayer. AB - In the companion paper to this work, we described development of a new type of hydrogen exchange (HX) mass spectrometry (MS) measurement that integrates Langmuir monolayers. With Langmuir monolayers, the lipid packing density can be reproducibly controlled and changed as desired. Analysis of HX in proteins that may undergo conformational changes as a function of lipid packing (for example, conformational rearrangements after insertion into a lipid layer) are then possible. We previously used neutron reflection to characterize just such a conformational change in the myristoylated HIV-1 Nef protein (myrNef): at high lipid packing density, myrNef could not insert into the lipids and maintained a compact conformation adjacent to the monolayer, whereas at lower lipid packing density, myrNef was able to insert N-terminal arm residues, causing displacement of the core domain away from the monolayer. In order to locate where conformation may have been altered by lipid association, we applied the HX MS Langmuir monolayer method to myrNef associated with monolayers of packing densities identical to those used for the prior neutron reflection measurements. The results show that the N-terminal region and the C-terminal unstructured loop undergo conformational changes when associated with a low density lipid monolayer. The results are not consistent with the hypothesis of myrNef dimerization upon membrane association in the absence of other myrNef binding partners. The HX MS Langmuir monolayer method provides new and meaningful information for myrNef that helps explain necessary conformational changes required for function at the membrane. PMID- 26133570 TI - 2015 ACC/HRS/SCAI Left Atrial Appendage Occlusion Device Societal Overview. PMID- 26133571 TI - Mother-Infant Contingent Vocalizations in 11 Countries. AB - Mother-infant vocal interactions serve multiple functions in child development, but it remains unclear whether key features of these interactions are community common or community-specific. We examined rates, interrelations, and contingencies of vocal interactions in 684 mothers and their 51/2-month-old infants in diverse communities in 11 countries (Argentina, Belgium, Brazil, Cameroon, France, Israel, Italy, Japan, Kenya, South Korea, and the United States). Rates of mothers' and infants' vocalizations varied widely across communities and were uncorrelated. However, collapsing the data across communities, we found that mothers' vocalizations to infants were contingent on the offset of the infants' nondistress vocalizing, infants' vocalizations were contingent on the offset of their mothers' vocalizing, and maternal and infant contingencies were significantly correlated. These findings point to the beginnings of dyadic conversational turn taking. Despite broad differences in the overall talkativeness of mothers and infants, maternal and infant contingent vocal responsiveness is found across communities, supporting essential functions of turn taking in early-childhood socialization. PMID- 26133572 TI - Computer Game Play Reduces Intrusive Memories of Experimental Trauma via Reconsolidation-Update Mechanisms. AB - Memory of a traumatic event becomes consolidated within hours. Intrusive memories can then flash back repeatedly into the mind's eye and cause distress. We investigated whether reconsolidation-the process during which memories become malleable when recalled-can be blocked using a cognitive task and whether such an approach can reduce these unbidden intrusions. We predicted that reconsolidation of a reactivated visual memory of experimental trauma could be disrupted by engaging in a visuospatial task that would compete for visual working memory resources. We showed that intrusive memories were virtually abolished by playing the computer game Tetris following a memory-reactivation task 24 hr after initial exposure to experimental trauma. Furthermore, both memory reactivation and playing Tetris were required to reduce subsequent intrusions (Experiment 2), consistent with reconsolidation-update mechanisms. A simple, noninvasive cognitive-task procedure administered after emotional memory has already consolidated (i.e., > 24 hours after exposure to experimental trauma) may prevent the recurrence of intrusive memories of those emotional events. PMID- 26133573 TI - Structural Features of a Bacteroidetes-Affiliated Cellulase Linked with a Polysaccharide Utilization Locus. AB - Previous gene-centric analysis of a cow rumen metagenome revealed the first potentially cellulolytic polysaccharide utilization locus, of which the main catalytic enzyme (AC2aCel5A) was identified as a glycoside hydrolase (GH) family 5 endo-cellulase. Here we present the 1.8 A three-dimensional structure of AC2aCel5A, and characterization of its enzymatic activities. The enzyme possesses the archetypical (beta/alpha)8-barrel found throughout the GH5 family, and contains the two strictly conserved catalytic glutamates located at the C terminal ends of beta-strands 4 and 7. The enzyme is active on insoluble cellulose and acts exclusively on linear beta-(1,4)-linked glucans. Co crystallization of a catalytically inactive mutant with substrate yielded a 2.4 A structure showing cellotriose bound in the -3 to -1 subsites. Additional electron density was observed between Trp178 and Trp254, two residues that form a hydrophobic "clamp", potentially interacting with sugars at the +1 and +2 subsites. The enzyme's active-site cleft was narrower compared to the closest structural relatives, which in contrast to AC2aCel5A, are also active on xylans, mannans and/or xyloglucans. Interestingly, the structure and function of this enzyme seem adapted to less-substituted substrates such as cellulose, presumably due to the insufficient space to accommodate the side-chains of branched glucans in the active-site cleft. PMID- 26133574 TI - MicroRNA let-7b-regulated epidermal stem cell proliferation in hypertrophied anal papillae. AB - The present study investigated the role of epidermal stem cell-expressed microRNA let-7b in the pathogenesis of hypertrophied anal papillae. Hypertrophied anal papillae were examined for the presence of epidermal stem cells. Epidermal stem cells were identified using flow cytometry and immunofluorescent staining for the cell surface markers, integrin alpha6 and integrin beta1 subunits. Expression levels of microRNA let-7b in alpha6+/beta1+and alpha6-/beta1-cells were compared using reverse transcription-quantitative polymerase chain reaction and northern blotting. Lentivirus-mediated expression of microRNA let-7b in epidermal stem cells was utilized in order to study the effects of this microRNA on the cell cycle proteins, cyclin D1 (CCND1) and cyclin-dependent kinase 4 (CDK4). MicroRNA let-7b-overexpressing cells were examined using flow cytometry, in order to determine the effects of the microRNA on cell cycle progression. alpha6+/beta1+epidermal stem cells were identified in hypertrophic anal papillae. Following isolation and enrichment of the alpha6+/beta1+population, these cells were found to have a rapid rate of proliferation in vitro. The expression of cell cycle-related proteins was elevated in this population, compared with that in alpha6-/beta1-cells. The expression of microRNA let-7b in alpha6+/beta1+epidermal stem cells was significantly lower than that in alpha6-/beta1-cells. Two microRNA let-7b target genes, CCND1 and CDK4, were found to be upregulated in alpha6+/beta1+cells. When the exogenous precursor, microRNA let-7, was overexpressed in alpha6+/beta1+ epidermal stem cells, the cell proliferation rate was significantly lower than that in cells expressing microRNA let-7 containing a mutated seed sequence. The addition of exogenous microRNA let-7 resulted in an increased expression level of mature microRNA let-7b, while the expression of CCND1 and CDK4 was reduced. Epidermal stem cells transfected with microRNA let-7b were arrested in the G2/M phase and the percentage of cells in S-phase was significantly reduced. In conclusion, let-7b expression results in upregulation of the cell cycle-related proteins, CCND1 and CDK4, resulting in the excessive proliferation that leads to the formation of hypertrophic anal papillae. PMID- 26133575 TI - Systematic review and meta-analysis of hepatic arterial infusion chemotherapy as bridging therapy for colorectal liver metastases. AB - BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has been shown to be beneficial in the management of unresectable colorectal liver metastases (CRLM). This systematic review evaluates the potential role of HAIC as a neoadjuvant downstaging therapy, prior to hepatic resection with curative intent for initially unresectable CRLM. METHODS: A literature search was conducted using Pubmed, EMBASE and Medline databases from January 2000 to November 2013. Studies adopting HAIC as a neoadjuvant bridging therapy for hepatic resection for CRLM were included. RESULTS: Eleven studies (n = 1514) were included. HAIC response rate was 50% and achieved conversion to surgery rate in 18% of patients. The median overall and 5-year survival for patients who underwent conversion to hepatectomy was 53 months and 49% compared to 16 months and 3% for patients who did not undergo surgery. Meta-analysis demonstrated strong association between hepatectomy and improved 5-year survival (RR 0.56, 95% CI = 0.48-0.65, Z = 7.26, p < 0.00001). CONCLUSION: For patients presenting with unresectable CRLM, HAIC in conjunction with current systemic chemotherapy may allow some patients to undergo resection and potentially provide long-term survival. PMID- 26133576 TI - Is radioembolization ((90)Y) better than doxorubicin drug eluting beads (DEBDOX) for hepatocellular carcinoma with portal vein thrombosis? A retrospective analysis. AB - INTRODUCTION: This study compares radioembolization ((90)Y) versus doxorubicin drug eluting beads (DEBDOX) in the treatment of unresectable hepatocellular carcinoma with portal vein thrombosis. METHODS: Using our prospectively maintained, multi-center, non-controlled intra-arterial therapy registry, we identified 28 consecutive patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT) treated with DEBDOX and 20 with (90)Y. Follow-up protocol consisted of a 3-phase CT scan of the liver within 3 months post-treatment. Tumor response rates were measured according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. RESULTS: There were 65 and 29 treatments in the DEBDOX and (90)Y groups respectively. Median age of DEBDOX was 59.8 (35-81) and (90)Y was 66.5 (49-82) years. A defined number of lesions were seen in 78% DEBDOX and 50% (90)Y patients. Patients were similar in the remaining 8 baseline characteristics including performance status, Child Pugh and extent of PVT. There were fewer overall side effects in the DEBDOX group compared to the (90)Y group (11% vs 39%; P = 0.03). There was better disease control (mRECIST) in the DEBDOX group compared to the (90)Y group (67% vs 20%; P = 0.0014). Median survival times were 10 months in DEBDOX and 3 months in the (90)Y group respectively from first treatment (log-rank, P = 0.037). CONCLUSION: DEBDOX is safe for patients with HCC and PVT and may have lower toxicity than (90)Y. It may also provide better disease control and survival benefit. Further studies are warranted to validate our observations and to determine if current clinical practice should be altered. PMID- 26133577 TI - p62 regulates CD40-mediated NFkappaB activation in macrophages through interaction with TRAF6. AB - CD40 is a member of the tumor necrosis factor (TNF) receptor family. Activation induced recruitment of adapter proteins, so-called TNF-receptor-associated factors (TRAFs) to the cytoplasmic tail of CD40 triggers signaling cascades important in the immune system, but has also been associated with excessive inflammation in diseases such as atherosclerosis and rheumatoid arthritis. Especially, pro-inflammatory nuclear factor kappaB (NFkappaB) signaling emanating from CD40-associated TRAF6 appears to be a key pathogenic driving force. Consequently, targeting the CD40-TRAF6 interaction is emerging as a promising therapeutic strategy, but the underlying molecular machinery of this signaling axis is to date poorly understood. Here, we identified the multifunctional adaptor protein p62 as a critical regulator in CD40-mediated NFkappaB signaling via TRAF6. CD40 activation triggered formation of a TRAF6-p62 complex. Disturbing this interaction tremendously reduced CD40-mediated NFkappaB signaling in macrophages, while TRAF6-independent signaling pathways remained unaffected. This highlights p62 as a potential target in hyper-inflammatory, CD40-associated pathologies. PMID- 26133578 TI - Built to fight: variable loading conditions and stress distribution in stag beetle jaws. AB - Designing very robust structures in an efficient way is a reoccurring challenge in engineering. For male stag beetle weaponry, the solution to this problem was evolved by natural and sexual selection. Stag beetle armature is adapted to perform under extreme circumstances: male stag beetles fight pugnacious battles over females, by using their extremely large jaws as ferocious weapons. During violent encounters, these jaws have to withstand forces with a wide range of unpredictable directions at several application points. We constructed 1020 finite element models with different input forces to investigate how the male jaws are structurally adapted to avoid failure. The cross-sectional shape of the jaw is adapted to provide robustness against the reaction forces of biting. Nevertheless, the jaw's shape cannot prevent the fact that bite forces induce relatively high material stresses compared to other force directions. Also, males do not confine themselves in combats to bite with the most robust jaw regions. Both observations emphasize the usefulness of bite force modulation to avoid jaw failure. This is likely effectuated by a sensory network in the jaw exoskeleton, as sensor densities are nicely correlated to the maximal material stress caused by 510 different loading directions. Probably, stag beetles use this sensory information to adjust their fighting strategy as well. Finally, male jaws also need to resist the forceful bites inflicted by opponents. Even though this loading applies at other locations along the jaw, and bends the jaw in the opposite direction, our models show that the jaws are equally robust against these external forces as they are against the forces caused by their own biting. PMID- 26133580 TI - POINT/COUNTERPOINT: Systemic alpha-particles are likely to yield more important advances in radiotherapy than are protons. PMID- 26133579 TI - Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs. AB - BACKGROUND: Genome editing (GE) is a method that enables specific nucleotides in the genome of an individual to be changed. To date, use of GE in livestock has focussed on simple traits that are controlled by a few quantitative trait nucleotides (QTN) with large effects. The aim of this study was to evaluate the potential of GE to improve quantitative traits that are controlled by many QTN, referred to here as promotion of alleles by genome editing (PAGE). METHODS: Multiple scenarios were simulated to test alternative PAGE strategies for a quantitative trait. They differed in (i) the number of edits per sire (0 to 100), (ii) the number of edits per generation (0 to 500), and (iii) the extent of use of PAGE (i.e. editing all sires or only a proportion of them). The base line scenario involved selecting individuals on true breeding values (i.e., genomic selection only (GS only)-genomic selection with perfect accuracy) for several generations. Alternative scenarios complemented this base line scenario with PAGE (GS + PAGE). The effect of different PAGE strategies was quantified by comparing response to selection, changes in allele frequencies, the number of distinct QTN edited, the sum of absolute effects of the edited QTN per generation, and inbreeding. RESULTS: Response to selection after 20 generations was between 1.08 and 4.12 times higher with GS + PAGE than with GS only. Increases in response to selection were larger with more edits per sire and more sires edited. When the total resources for PAGE were limited, editing a few sires for many QTN resulted in greater response to selection and inbreeding compared to editing many sires for a few QTN. Between the scenarios GS only and GS + PAGE, there was little difference in the average change in QTN allele frequencies, but there was a major difference for the QTN with the largest effects. The sum of the effects of the edited QTN decreased across generations. CONCLUSIONS: This study showed that PAGE has great potential for application in livestock breeding programs, but inbreeding needs to be managed. PMID- 26133581 TI - Dosimetric characterization and organ dose assessment in digital breast tomosynthesis: Measurements and Monte Carlo simulations using voxel phantoms. AB - PURPOSE: Due to its capability to more accurately detect deep lesions inside the breast by removing the effect of overlying anatomy, digital breast tomosynthesis (DBT) has the potential to replace the standard mammography technique in clinical screening exams. However, the European Guidelines for DBT dosimetry are still a work in progress and there are little data available on organ doses other than to the breast. It is, therefore, of great importance to assess the dosimetric performance of DBT with respect to the one obtained with standard digital mammography (DM) systems. The aim of this work is twofold: (i) to study the dosimetric properties of a combined DBT/DM system (MAMMOMAT Inspiration Siemens((r))) for a tungsten/rhodium (W/Rh) anode/filter combination and (ii) to evaluate organs doses during a DBT examination. METHODS: For the first task, measurements were performed in manual and automatic exposure control (AEC) modes, using two homogeneous breast phantoms: a PMMA slab phantom and a 4 cm thick breast-shaped rigid phantom, with 50% of glandular tissue in its composition. Monte Carlo (MC) simulations were performed using Monte Carlo N-Particle eXtended v.2.7.0. A MC model was implemented to mimic DM and DBT acquisitions for a wide range of x-ray spectra (24 -34 kV). This was used to calculate mean glandular dose (MGD) and to compute series of backscatter factors (BSFs) that could be inserted into the DBT dosimetric formalism proposed by Dance et al. Regarding the second aim of the study, the implemented MC model of the clinical equipment, together with a female voxel phantom ("Laura"), was used to calculate organ doses considering a typical DBT acquisition. Results were compared with a standard two view mammography craniocaudal (CC) acquisition. RESULTS: Considering the AEC mode, the acquisition of a single CC view results in a MGD ranging from 0.53 +/- 0.07 mGy to 2.41 +/- 0.31 mGy in DM mode and from 0.77 +/- 0.11 mGy to 2.28 +/- 0.32 mGy in DBT mode. Regarding the BSF, the results achieved may lead to a MGD correction of about 6%, contributing to the improvement of the current guidelines used in these applications. Finally, considering the MC results obtained for the organ dose study, the radiation doses found for the tissues of the body other than the breast were in the range of tens of MUSv, and are in part comparable to the ones obtained in standard DM. Nevertheless, in a single DBT examination, some organs (such as lung and thyroid) receive higher doses (of about 9% and 21%, respectively) with respect to the CC DM acquisition. CONCLUSIONS: Taking into account an average breast with a thickness of 4.5 cm, the MGDs for DM and DBT acquisitions were below the achievable value (2.0 mGy) defined by the European protocol. Additionally, in the case of a fusion imaging study (DM + DBT), the MGD for a 4.5 cm thick breast is of the order of 1.88 +/- 0.36 mGy. Finally, organ dose evaluations underline the need to improve awareness concerning dose estimation of DBT exams for some organs, especially when radiation risk is assessed by using the effective dose. PMID- 26133583 TI - Exploitation of temporal redundancy in compressed sensing reconstruction of fMRI studies with a prior-based algorithm (PICCS). AB - PURPOSE: Compressed sensing is a technique used to accelerate magnetic resonance imaging (MRI) acquisition without compromising image quality. While it has proven particularly useful in dynamic imaging procedures such as cardiac cine, very few authors have applied it to functional magnetic resonance imaging (fMRI). The purpose of the present study was to check whether the prior image constrained compressed sensing (PICCS) algorithm, which is based on an available prior image, can improve the statistical maps in fMRI better than other strategies that also exploit temporal redundancy. METHODS: PICCS was compared to spatiotemporal total variation (TTV) and k-t FASTER, since they have already demonstrated high performance and robustness in other MRI applications, such as cardiac cine MRI and resting state fMRI, respectively. The prior image for PICCS was the average of all undersampled data. Both PICCS and TTV were solved using the split Bregman formulation. K-t FASTER algorithm relies on matrix completion to reconstruct the undersampled k-spaces. The three algorithms were evaluated using two datasets with high and low signal-to-noise ratio (SNR)-BOLD contrast-acquired in a 7 T preclinical MRI scanner and retrospectively undersampled at various rates (i.e., acceleration factors). The authors evaluated their performance in terms of the sensitivity/specificity of BOLD detection through receiver operating characteristic curves and by visual inspection of the statistical maps. RESULTS: With high SNR studies, PICCS performed similarly to the state-of-the-art algorithms TTV and k-t FASTER and provided consistent BOLD signal at the ROI. In scenarios with low SNR and high acceleration factors, PICCS still provided consistent maps and higher sensitivity/specificity than TTV, whereas k-t FASTER failed to provide significant maps. CONCLUSIONS: The authors performed a comparison between three reconstructions (PICCS, TTV, and k-t FASTER) that exploit temporal redundancy in fMRI. The prior-based algorithm, PICCS, preserved BOLD activation and sensitivity/specificity better than TTV and k-t FASTER in noisy scenarios. The PICCS algorithm can potentially reach an acceleration factor of *8 and still provide BOLD contrast in the ROI with an area under the curve over 0.99. PMID- 26133582 TI - Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies. AB - PURPOSE: Previous studies have demonstrated how imaging of the breast with patients lying prone using a supportive positioning device markedly facilitates longitudinal and/or multimodal image registration. In this contribution, the authors' primary objective was to determine if there are differences in the standardized uptake value (SUV) derived from [(18)F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in breast tumors imaged in the standard supine position and in the prone position using a specialized positioning device. METHODS: A custom positioning device was constructed to allow for breast scanning in the prone position. Rigid and nonrigid phantom studies evaluated differences in prone and supine PET. Clinical studies comprised 18F-FDG-PET of 34 patients with locally advanced breast cancer imaged in the prone position (with the custom support) followed by imaging in the supine position (without the support). Mean and maximum values (SUVpeak and SUVmax, respectively) were obtained from tumor regions-of-interest for both positions. Prone and supine SUV were linearly corrected to account for the differences in 18F-FDG uptake time. Correlation, Bland-Altman, and nonparametric analyses were performed on uptake time-corrected and uncorrected data. RESULTS: SUV from the rigid PET breast phantom imaged in the prone position with the support device was 1.9% lower than without the support device. In the nonrigid PET breast phantom, prone SUV with the support device was 5.0% lower than supine SUV without the support device. In patients, the median (range) difference in uptake time between prone and supine scans was 16.4 min (13.4-30.9 min), which was significantly-but not completely-reduced by the linear correction method. SUVpeak and SUVmax from prone versus supine scans were highly correlated, with concordance correlation coefficients of 0.91 and 0.90, respectively. Prone SUVpeak and SUVmax were significantly lower than supine in both original and uptake time-adjusted data across a range of index times (P < < 0.0001, Wilcoxon signed rank test). Before correcting for uptake time differences, Bland-Altman analyses revealed proportional bias between prone and supine measurements (SUVpeak and SUVmax) that increased with higher levels of FDG uptake. After uptake time correction, this bias was significantly reduced (P < 0.01). Significant prone-supine differences, with regard to the spatial distribution of lesions relative to isocenter, were observed between the two scan positions, but this was poorly correlated with the residual (uptake time corrected) prone-supine SUVpeak difference (P = 0.78). CONCLUSIONS: Quantitative 18F-FDG-PET/CT of the breast in the prone position is not deleteriously affected by the support device but yields SUV that is consistently lower than those obtained in the standard supine position. SUV differences between scans arising from FDG uptake time differences can be substantially reduced, but not removed entirely, with the current correction method. SUV from the two scan orientations is quantitatively different and should not be assumed equivalent or interchangeable within the same subject. These findings have clinical relevance in that they underscore the importance of patient positioning while scanning as a clinical variable that must be accounted for with longitudinal PET measurement, for example, in the assessment of treatment response. PMID- 26133584 TI - Multiatlas whole heart segmentation of CT data using conditional entropy for atlas ranking and selection. AB - PURPOSE: Cardiac computed tomography (CT) is widely used in clinical diagnosis of cardiovascular diseases. Whole heart segmentation (WHS) plays a vital role in developing new clinical applications of cardiac CT. However, the shape and appearance of the heart can vary greatly across different scans, making the automatic segmentation particularly challenging. The objective of this work is to develop and evaluate a multiatlas segmentation (MAS) scheme using a new atlas ranking and selection algorithm for automatic WHS of CT data. Research on different MAS strategies and their influence on WHS performance are limited. This work provides a detailed comparison study evaluating the impacts of label fusion, atlas ranking, and sizes of the atlas database on the segmentation performance. METHODS: Atlases in a database were registered to the target image using a hierarchical registration scheme specifically designed for cardiac images. A subset of the atlases were selected for label fusion, according to the authors' proposed atlas ranking criterion which evaluated the performance of each atlas by computing the conditional entropy of the target image given the propagated atlas labeling. Joint label fusion was used to combine multiple label estimates to obtain the final segmentation. The authors used 30 clinical cardiac CT angiography (CTA) images to evaluate the proposed MAS scheme and to investigate different segmentation strategies. RESULTS: The mean WHS Dice score of the proposed MAS method was 0.918 +/- 0.021, and the mean runtime for one case was 13.2 min on a workstation. This MAS scheme using joint label fusion generated significantly better Dice scores than the other label fusion strategies, including majority voting (0.901 +/- 0.276, p < 0.01), locally weighted voting (0.905 +/- 0.0247, p < 0.01), and probabilistic patch-based fusion (0.909 +/- 0.0249, p < 0.01). In the atlas ranking study, the proposed criterion based on conditional entropy yielded a performance curve with higher WHS Dice scores compared to the conventional schemes (p < 0.03). In the atlas database study, the authors showed that the MAS using larger atlas databases generated better performance curves than the MAS using smaller ones, indicating larger atlas databases could produce more accurate segmentation. CONCLUSIONS: The authors have developed a new MAS framework for automatic WHS of CTA and investigated alternative implementations of MAS. With the proposed atlas ranking algorithm and joint label fusion, the MAS scheme is able to generate accurate segmentation within practically acceptable computation time. This method can be useful for the development of new clinical applications of cardiac CT. PMID- 26133585 TI - Tailoring automatic exposure control toward constant detectability in digital mammography. AB - PURPOSE: The automatic exposure control (AEC) modes of most full field digital mammography (FFDM) systems are set up to hold pixel value (PV) constant as breast thickness changes. This paper proposes an alternative AEC mode, set up to maintain some minimum detectability level, with the ultimate goal of improving object detectability at larger breast thicknesses. METHODS: The default "opdose" AEC mode of a Siemens MAMMOMAT Inspiration FFDM system was assessed using poly(methyl methacrylate) (PMMA) of thickness 20, 30, 40, 50, 60, and 70 mm to find the tube voltage and anode/filter combination programmed for each thickness; these beam quality settings were used for the modified AEC mode. Detectability index (d'), in terms of a non-prewhitened model observer with eye filter, was then calculated as a function of tube current-time product (mAs) for each thickness. A modified AEC could then be designed in which detectability never fell below some minimum setting for any thickness in the operating range. In this study, the value was chosen such that the system met the achievable threshold gold thickness (Tt) in the European guidelines for the 0.1 mm diameter disc (i.e., Tt <= 1.10 MUm gold). The default and modified AEC modes were compared in terms of contrast-detail performance (Tt), calculated detectability (d'), signal difference-to-noise ratio (SDNR), and mean glandular dose (MGD). The influence of a structured background on object detectability for both AEC modes was examined using a CIRS BR3D phantom. Computer-based CDMAM reading was used for the homogeneous case, while the images with the BR3D background were scored by human observers. RESULTS: The default opdose AEC mode maintained PV constant as PMMA thickness increased, leading to a reduction in SDNR for the homogeneous background 39% and d' 37% in going from 20 to 70 mm; introduction of the structured BR3D plate changed these figures to 22% (SDNR) and 6% (d'), respectively. Threshold gold thickness (0.1 mm diameter disc) for the default AEC mode in the homogeneous background increased by 62% in going from 20 to 70 mm PMMA thickness; in the structured background, the increase was 39%. Implementation of the modified mode entailed an increase in mAs at PMMA thicknesses >40 mm; the modified AEC held threshold gold thickness constant above 40 mm PMMA with a maximum deviation of 5% in the homogeneous background and 3% in structured background. SDNR was also held constant with a maximum deviation of 4% and 2% for the homogeneous and the structured background, respectively. These results were obtained with an increase of MGD between 15% and 73% going from 40 to 70 mm PMMA thickness. CONCLUSIONS: This work has proposed and implemented a modified AEC mode, tailored toward constant detectability at larger breast thickness, i.e., above 40 mm PMMA equivalent. The desired improvement in object detectability could be obtained while maintaining MGD within the European guidelines achievable dose limit. (A study designed to verify the performance of the modified mode using more clinically realistic data is currently underway.). PMID- 26133586 TI - Correction of MRI-induced geometric distortions in whole-body small animal PET MRI. AB - PURPOSE: The fusion of positron emission tomography (PET) and magnetic resonance imaging (MRI) data can be a challenging task in whole-body PET-MRI. The quality of the registration between these two modalities in large field-of-views (FOV) is often degraded by geometric distortions of the MRI data. The distortions at the edges of large FOVs mainly originate from MRI gradient nonlinearities. This work describes a method to measure and correct for these kind of geometric distortions in small animal MRI scanners to improve the registration accuracy of PET and MRI data. METHODS: The authors have developed a geometric phantom which allows the measurement of geometric distortions in all spatial axes via control points. These control points are detected semiautomatically in both PET and MRI data with a subpixel accuracy. The spatial transformation between PET and MRI data is determined with these control points via 3D thin-plate splines (3D TPS). The transformation derived from the 3D TPS is finally applied to real MRI mouse data, which were acquired with the same scan parameters used in the phantom data acquisitions. Additionally, the influence of the phantom material on the homogeneity of the magnetic field is determined via field mapping. RESULTS: The spatial shift according to the magnetic field homogeneity caused by the phantom material was determined to a mean of 0.1 mm. The results of the correction show that distortion with a maximum error of 4 mm could be reduced to less than 1 mm with the proposed correction method. Furthermore, the control point-based registration of PET and MRI data showed improved congruence after correction. CONCLUSIONS: The developed phantom has been shown to have no considerable negative effect on the homogeneity of the magnetic field. The proposed method yields an appropriate correction of the measured MRI distortion and is able to improve the PET and MRI registration. Furthermore, the method is applicable to whole-body small animal imaging routines including different standard MRI sequences. PMID- 26133587 TI - A novel computer aided breast mass detection scheme based on morphological enhancement and SLIC superpixel segmentation. AB - PURPOSE: To develop a computer-aided detection (CAD) scheme for mass detection on digitized mammograms that achieves a high sensitivity while maintaining a low false positive (FP) rate using morphological enhancement and simple linear iterative clustering (SLIC) method. METHODS: The authors developed a multiple stage method for breast mass detection. The proposed CAD scheme consists of five major components: (1) preprocessing based on morphological enhancement, which enhances mass-like patterns while removing unrelated background clutters, (2) segmentation of mass candidates based on the SLIC method, which groups mass and background tissue into different regions, (3) prescreening of suspicious regions using rule-based classification that eliminates regions unlikely to represent masses, (4) potential lesion contour refinement based on distance regularized level set evolution, and (5) FP reduction based on feature extraction and an ensemble of undersampled support vector machines. Two datasets were built to design and evaluate the system: a mass dataset containing 187 cases (386 mammograms) and a nonmass dataset containing 88 mammograms. All cases were acquired from the digital database for screening mammography (DDSM). Approximately two thirds of the available masses were used for training the system, and the remaining masses and nonmass dataset were used for testing. RESULTS: Testing of the proposed CAD system on the mass dataset yielded a mass based sensitivity of 98.55%, 97.10%, 92.75% at 0.84, 0.63, 0.55 FP mark/image, respectively. Tested on the nonmass dataset, the scheme showed a FP rate of 0.55, 0.34, 0.30 mark/image. CONCLUSIONS: The results indicate that the system is promising in improving the performance of current CAD systems by reducing FP rate while achieving relatively high sensitivity. PMID- 26133588 TI - Technical Note: Improvements in geant4 energy-loss model and the effect on low energy electron transport in liquid water. AB - PURPOSE: The geant4-DNA physics models are upgraded by a more accurate set of electron cross sections for ionization and excitation in liquid water. The impact of the new developments on low-energy electron transport simulations by the geant4 Monte Carlo toolkit is examined for improving its performance in dosimetry applications at the subcellular and nanometer level. METHODS: The authors provide an algorithm for an improved implementation of the Emfietzoglou model dielectric response function of liquid water used in the geant4-DNA existing model. The algorithm redistributes the imaginary part of the dielectric function to ensure a physically motivated behavior at the binding energies, while retaining all the advantages of the original formulation, e.g., the analytic properties and the fulfillment of the f-sum-rule. In addition, refinements in the exchange and perturbation corrections to the Born approximation used in the geant4-DNA existing model are also made. RESULTS: The new ionization and excitation cross sections are significantly different from those of the geant4-DNA existing model. In particular, excitations are strongly enhanced relative to ionizations, resulting in higher W-values and less diffusive dose-point-kernels at sub-keV electron energies. CONCLUSIONS: An improved energy-loss model for the excitation and ionization of liquid water by low-energy electrons has been implemented in geant4-DNA. The suspiciously low W-values and the unphysical long tail in the dose-point-kernel have been corrected owing to a different partitioning of the dielectric function. PMID- 26133589 TI - Online adaptation and verification of VMAT. AB - PURPOSE: This work presents a method for fast volumetric modulated arc therapy (VMAT) adaptation in response to interfraction anatomical variations. Additionally, plan parameters extracted from the adapted plans are used to verify the quality of these plans. The methods were tested as a prostate class solution and compared to replanning and to their current clinical practice. METHODS: The proposed VMAT adaptation is an extension of their previous intensity modulated radiotherapy (IMRT) adaptation. It follows a direct (forward) planning approach: the multileaf collimator (MLC) apertures are corrected in the beam's eye view (BEV) and the monitor units (MUs) are corrected using point dose calculations. All MLC and MU corrections are driven by the positions of four fiducial points only, without need for a full contour set. Quality assurance (QA) of the adapted plans is performed using plan parameters that can be calculated online and that have a relation to the delivered dose or the plan quality. Five potential parameters are studied for this purpose: the number of MU, the equivalent field size (EqFS), the modulation complexity score (MCS), and the components of the MCS: the aperture area variability (AAV) and the leaf sequence variability (LSV). The full adaptation and its separate steps were evaluated in simulation experiments involving a prostate phantom subjected to various interfraction transformations. The efficacy of the current VMAT adaptation was scored by target mean dose (CTVmean), conformity (CI95%), tumor control probability (TCP), and normal tissue complication probability (NTCP). The impact of the adaptation on the plan parameters (QA) was assessed by comparison with prediction intervals (PI) derived from a statistical model of the typical variation of these parameters in a population of VMAT prostate plans (n = 63). These prediction intervals are the adaptation equivalent of the tolerance tables for couch shifts in the current clinical practice. RESULTS: The proposed adaptation of a two-arc VMAT plan resulted in the intended CTVmean (Delta <= 3%) and TCP (DeltaTCP <= 0.001). Moreover, the method assures the intended CI95% (Delta <= 11%) resulting in lowered rectal NTCP for all cases. Compared to replanning, their adaptation is faster (13 s vs 10 min) and more intuitive. Compared to the current clinical practice, it has a better protection of the healthy tissue. Compared to IMRT, VMAT is more robust to anatomical variations, but it is also less sensitive to the different correction steps. The observed variations of the plan parameters in their database included a linear dependence on the date of treatment planning and on the target radius. The MCS is not retained as QA metric due to a contrasting behavior of its components (LSV and AAV). If three out of four plan parameters (MU, EqFS, AAV, and LSV) need to lie inside a 50% prediction interval (3/4 50%PI), all adapted plans will be accepted. In contrast, all replanned plans do not meet this loose criterion, mainly because they have no connection to the initially optimized and verified plan. CONCLUSIONS: A direct (forward) VMAT adaptation performs equally well as (inverse) replanning but is faster and can be extended to real-time adaptation. The prediction intervals for the machine parameters are equivalent to the tolerance tables for couch shifts in the current clinical practice. A 3/4-50%PI QA criterion accepts all the adapted plans but rejects all the replanned plans. PMID- 26133590 TI - Technical Note: Experimental determination of the effective point of measurement of two cylindrical ionization chambers in a clinical proton beam. AB - PURPOSE: IAEA TRS-398 notes that cylindrical ionization chambers are preferred for reference proton dosimetry. If a cylindrical ionization chamber is used in a phantom to measure the dose as a function of depth, the effective point of measurement (EPOM) must be taken into account. IAEA TRS-398 recommends a displacement of 0.75 times the inner cavity radius (0.75R) for heavy ion beams. Theoretical models by Palmans and by Bhullar and Watchman confirmed this value. However, the experimental results vary from author to author. The purpose of this study is to accurately measure the displacement and explain the past experimental discrepancies. METHODS: In this work, we measured the EPOM of cylindrical ionization chambers with high accuracy by comparing the Bragg-peak position obtained with cylindrical ionization chambers (PTW 30013, PTW 31016) to that obtained using a plane-parallel ionization chamber (PTW 34045). RESULTS: The EPOMs of PTW 30013 and 31016 were shifted by 0.92 +/- 0.07 R with R = 3.05 mm and 0.90 +/- 0.14 R with R = 1.45 mm, respectively, from the reference point toward the source. CONCLUSIONS: The EPOMs obtained were greater than the value of 0.75R proposed by the IAEA TRS-398 and the analytical results. PMID- 26133592 TI - Development and evaluation of aperture-based complexity metrics using film and EPID measurements of static MLC openings. AB - PURPOSE: Complexity metrics have been suggested as a complement to measurement based quality assurance for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). However, these metrics have not yet been sufficiently validated. This study develops and evaluates new aperture-based complexity metrics in the context of static multileaf collimator (MLC) openings and compares them to previously published metrics. METHODS: This study develops the converted aperture metric and the edge area metric. The converted aperture metric is based on small and irregular parts within the MLC opening that are quantified as measured distances between MLC leaves. The edge area metric is based on the relative size of the region around the edges defined by the MLC. Another metric suggested in this study is the circumference/area ratio. Earlier defined aperture-based complexity metrics-the modulation complexity score, the edge metric, the ratio monitor units (MU)/Gy, the aperture area, and the aperture irregularity-are compared to the newly proposed metrics. A set of small and irregular static MLC openings are created which simulate individual IMRT/VMAT control points of various complexities. These are measured with both an amorphous silicon electronic portal imaging device and EBT3 film. The differences between calculated and measured dose distributions are evaluated using a pixel-by-pixel comparison with two global dose difference criteria of 3% and 5%. The extent of the dose differences, expressed in terms of pass rate, is used as a measure of the complexity of the MLC openings and used for the evaluation of the metrics compared in this study. The different complexity scores are calculated for each created static MLC opening. The correlation between the calculated complexity scores and the extent of the dose differences (pass rate) are analyzed in scatter plots and using Pearson's r-values. RESULTS: The complexity scores calculated by the edge area metric, converted aperture metric, circumference/area ratio, edge metric, and MU/Gy ratio show good linear correlation to the complexity of the MLC openings, expressed as the 5% dose difference pass rate, with Pearson's r-values of -0.94, -0.88, -0.84, -0.89, and -0.82, respectively. The overall trends for the 3% and 5% dose difference evaluations are similar. CONCLUSIONS: New complexity metrics are developed. The calculated scores correlate to the complexity of the created static MLC openings. The complexity of the MLC opening is dependent on the penumbra region relative to the area of the opening. The aperture-based complexity metrics that combined either the distances between the MLC leaves or the MLC opening circumference with the aperture area show the best correlation with the complexity of the static MLC openings. PMID- 26133591 TI - Computer-aided pulmonary image analysis in small animal models. AB - PURPOSE: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. METHODS: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors' system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. RESULTS: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT'09 data set. CONCLUSIONS: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases. PMID- 26133593 TI - Modeling of electrodes and implantable pulse generator cases for the analysis of implant tip heating under MR imaging. AB - PURPOSE: The authors' purpose is to model the case of an implantable pulse generator (IPG) and the electrode of an active implantable medical device using lumped circuit elements in order to analyze their effect on radio frequency induced tissue heating problem during a magnetic resonance imaging (MRI) examination. METHODS: In this study, IPG case and electrode are modeled with a voltage source and impedance. Values of these parameters are found using the modified transmission line method (MoTLiM) and the method of moments (MoM) simulations. Once the parameter values of an electrode/IPG case model are determined, they can be connected to any lead, and tip heating can be analyzed. To validate these models, both MoM simulations and MR experiments were used. The induced currents on the leads with the IPG case or electrode connections were solved using the proposed models and the MoTLiM. These results were compared with the MoM simulations. In addition, an electrode was connected to a lead via an inductor. The dissipated power on the electrode was calculated using the MoTLiM by changing the inductance and the results were compared with the specific absorption rate results that were obtained using MoM. Then, MRI experiments were conducted to test the IPG case and the electrode models. To test the IPG case, a bare lead was connected to the case and placed inside a uniform phantom. During a MRI scan, the temperature rise at the lead was measured by changing the lead length. The power at the lead tip for the same scenario was also calculated using the IPG case model and MoTLiM. Then, an electrode was connected to a lead via an inductor and placed inside a uniform phantom. During a MRI scan, the temperature rise at the electrode was measured by changing the inductance and compared with the dissipated power on the electrode resistance. RESULTS: The induced currents on leads with the IPG case or electrode connection were solved for using the combination of the MoTLiM and the proposed lumped circuit models. These results were compared with those from the MoM simulations. The mean square error was less than 9%. During the MRI experiments, when the IPG case was introduced, the resonance lengths were calculated to have an error less than 13%. Also the change in tip temperature rise at resonance lengths was predicted with less than 4% error. For the electrode experiments, the value of the matching impedance was predicted with an error less than 1%. CONCLUSIONS: Electrical models for the IPG case and electrode are suggested, and the method is proposed to determine the parameter values. The concept of matching of the electrode to the lead is clarified using the defined electrode impedance and the lead Thevenin impedance. The effect of the IPG case and electrode on tip heating can be predicted using the proposed theory. With these models, understanding the tissue heating due to the implants becomes easier. Also, these models are beneficial for implant safety testers and designers. Using these models, worst case conditions can be determined and the corresponding implant test experiments can be planned. PMID- 26133594 TI - Statistical analysis of lung nodule volume measurements with CT in a large-scale phantom study. AB - PURPOSE: To determine inter-related factors that contribute substantially to measurement error of pulmonary nodule measurements with CT by assessing a large scale dataset of phantom scans and to quantitatively validate the repeatability and reproducibility of a subset containing nodules and CT acquisitions consistent with the Quantitative Imaging Biomarker Alliance (QIBA) metrology recommendations. METHODS: The dataset has about 40 000 volume measurements of 48 nodules (5-20 mm, four shapes, three radiodensities) estimated by a matched filter estimator from CT images involving 72 imaging protocols. Technical assessment was performed under a framework suggested by QIBA, which aimed to minimize the inconsistency of terminologies and techniques used in the literature. Accuracy and precision of lung nodule volume measurements were examined by analyzing the linearity, bias, variance, root mean square error (RMSE), repeatability, reproducibility, and significant and substantial factors that contribute to the measurement error. Statistical methodologies including linear regression, analysis of variance, and restricted maximum likelihood were applied to estimate the aforementioned metrics. The analysis was performed on both the whole dataset and a subset meeting the criteria proposed in the QIBA Profile document. RESULTS: Strong linearity was observed for all data. Size, slice thickness * collimation, and randomness in attachment to vessels or chest wall were the main sources of measurement error. Grouping the data by nodule size and slice thickness * collimation, the standard deviation (3.9%-28%), and RMSE (4.4%-68%) tended to increase with smaller nodule size and larger slice thickness. For 5, 8, 10, and 20 mm nodules with reconstruction slice thickness <=0.8, 3, 3, and 5 mm, respectively, the measurements were almost unbiased (-3.0% to 3.0%). Repeatability coefficients (RCs) were from 6.2% to 40%. Pitch of 0.9, detail kernel, and smaller slice thicknesses yielded better (smaller) RCs than those from pitch of 1.2, medium kernel, and larger slice thicknesses. Exposure showed no impact on RC. The overall reproducibility coefficient (RDC) was 45%, and reduced to about 20%-30% when the slice thickness and collimation were fixed. For nodules and CT imaging complying with the QIBA Profile (QIBA Profile subset), the measurements were highly repeatable and reproducible in spite of variations in nodule characteristics and imaging protocols. The overall measurement error was small and mostly due to the randomness in attachment. The bias, standard deviation, and RMSE grouped by nodule size and slice thickness * collimation in the QIBA Profile subset were within +/-3%, 4%, and 5%, respectively. RCs are within 11% and the overall RDC is equal to 11%. CONCLUSIONS: The authors have performed a comprehensive technical assessment of lung nodule volumetry with a matched-filter estimator from CT scans of synthetic nodules and identified the main sources of measurement error among various nodule characteristics and imaging parameters. The results confirm that the QIBA Profile set is highly repeatable and reproducible. These phantom study results can serve as a bound on the clinical performance achievable with volumetric CT measurements of pulmonary nodules. PMID- 26133595 TI - A new automated quantification algorithm for the detection and evaluation of focal liver lesions with contrast-enhanced ultrasound. AB - PURPOSE: Detect and classify focal liver lesions (FLLs) from contrast-enhanced ultrasound (CEUS) imaging by means of an automated quantification algorithm. METHODS: The proposed algorithm employs a sophisticated segmentation method to detect and contour focal lesions from 52 CEUS video sequences (30 benign and 22 malignant). Lesion detection involves wavelet transform zero crossings utilization as an initialization step to the Markov random field model toward the lesion contour extraction. After FLL detection across frames, time intensity curve (TIC) is computed which provides the contrast agents' behavior at all vascular phases with respect to adjacent parenchyma for each patient. From each TIC, eight features were automatically calculated and employed into the support vector machines (SVMs) classification algorithm in the design of the image analysis model. RESULTS: With regard to FLLs detection accuracy, all lesions detected had an average overlap value of 0.89 +/- 0.16 with manual segmentations for all CEUS frame-subsets included in the study. Highest classification accuracy from the SVM model was 90.3%, misdiagnosing three benign and two malignant FLLs with sensitivity and specificity values of 93.1% and 86.9%, respectively. CONCLUSIONS: The proposed quantification system that employs FLLs detection and classification algorithms may be of value to physicians as a second opinion tool for avoiding unnecessary invasive procedures. PMID- 26133596 TI - A rapid noninvasive characterization of CT x-ray sources. AB - PURPOSE: The aim of this study is to generate spatially varying half value layers (HVLs) that can be used to construct virtual equivalent source models of computed tomography (CT) x-ray sources for use in Monte Carlo CT dose computations. METHODS: To measure the spatially varying HVLs, the authors combined a cylindrical HVL measurement technique with the characterization of bowtie filter relative attenuation (COBRA) geometry. An apparatus given the name "HVL Jig" was fabricated to accurately position a real-time dosimeter off-isocenter while surrounded by concentric cylindrical aluminum filters (CAFs). In this geometry, each projection of the rotating x-ray tube is filtered by an identical amount of high-purity (type 1100 H-14) aluminum while the stationary radiation dose probe records an air kerma rate versus time waveform. The CAFs were progressively nested to acquire exposure data at increasing filtrations to calculate the HVL. Using this dose waveform and known setup geometry, each timestamp was related to its corresponding fan angle. Data were acquired using axial CT protocols (i.e., rotating tube and stationary patient table) at energies of 80, 100, and 120 kVp on a single CT scanner. These measurements were validated against the more laborious conventional step-and-shoot approach (stationary x-ray tube). RESULTS: At each energy, HVL data points from the COBRA-cylinder technique were fit to a trendline and compared with the conventional approach. The average relative difference in HVL between the two techniques was 1.3%. There was a systematic overestimation in HVL due to scatter contamination. CONCLUSIONS: The described method is a novel, rapid, accurate, and noninvasive approach that allows one to acquire the spatially varying fluence and HVL data using a single experimental setup in a minimum of three scans. These measurements can be used to characterize the CT beam in terms of the angle-dependent fluence and energy spectra along the bowtie filter direction, which can serve as input for accurate CT dose computations. PMID- 26133597 TI - Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with (131)I-metaiodobenzylguanidine with implications for the activity to administer. AB - PURPOSE: The aim was to investigate whole-body and red marrow absorbed doses in treatments of neuroblastoma (NB) and adult neuroendocrine tumors (NETs) with (131)I-metaiodobenzylguanidine and to propose a simple method for determining the activity to administer when dosimetric data for the individual patient are not available. METHODS: Nine NB patients and six NET patients were included, giving in total 19 treatments as four patients were treated twice. Whole-body absorbed doses were determined from dose-rate measurements and planar gamma-camera imaging. For six NB and five NET treatments, red marrow absorbed doses were also determined using the blood-based method. RESULTS: Dosimetric data from repeated administrations in the same patient were consistent. In groups of NB and NET patients, similar whole-body residence times were obtained, implying that whole body absorbed dose per unit of administered activity could be reasonably well described as a power function of the patient mass. For NB, this functional form was found to be consistent with dosimetric data from previously published studies. The whole-body to red marrow absorbed dose ratio was similar among patients, with values of 1.4 +/- 0.6-1.7 +/- 0.7 (1 standard deviation) in NB treatments and between 1.5 +/- 0.6 and 1.7 +/- 0.7 (1 standard deviation) in NET treatments. CONCLUSIONS: The consistency of dosimetric results between administrations for the same patient supports prescription of the activity based on dosimetry performed in pretreatment studies, or during the first administration in a fractionated schedule. The expressions obtained for whole body absorbed doses per unit of administered activity as a function of patient mass for NB and NET treatments are believed to be a useful tool to estimate the activity to administer at the stage when the individual patient biokinetics has not yet been measured. PMID- 26133598 TI - Investigating the limits of PET/CT imaging at very low true count rates and high random fractions in ion-beam therapy monitoring. AB - PURPOSE: External beam radiotherapy with protons and heavier ions enables a tighter conformation of the applied dose to arbitrarily shaped tumor volumes with respect to photons, but is more sensitive to uncertainties in the radiotherapeutic treatment chain. Consequently, an independent verification of the applied treatment is highly desirable. For this purpose, the irradiation induced beta(+)-emitter distribution within the patient is detected shortly after irradiation by a commercial full-ring positron emission tomography/x-ray computed tomography (PET/CT) scanner installed next to the treatment rooms at the Heidelberg Ion-Beam Therapy Center (HIT). A major challenge to this approach is posed by the small number of detected coincidences. This contribution aims at characterizing the performance of the used PET/CT device and identifying the best performing reconstruction algorithm under the particular statistical conditions of PET-based treatment monitoring. Moreover, this study addresses the impact of radiation background from the intrinsically radioactive lutetium-oxyorthosilicate (LSO)-based detectors at low counts. METHODS: The authors have acquired 30 subsequent PET scans of a cylindrical phantom emulating a patientlike activity pattern and spanning the entire patient counting regime in terms of true coincidences and random fractions (RFs). Accuracy and precision of activity quantification, image noise, and geometrical fidelity of the scanner have been investigated for various reconstruction algorithms and settings in order to identify a practical, well-suited reconstruction scheme for PET-based treatment verification. Truncated listmode data have been utilized for separating the effects of small true count numbers and high RFs on the reconstructed images. A corresponding simulation study enabled extending the results to an even wider range of counting statistics and to additionally investigate the impact of scatter coincidences. Eventually, the recommended reconstruction scheme has been applied to exemplary postirradiation patient data-sets. RESULTS: Among the investigated reconstruction options, the overall best results in terms of image noise, activity quantification, and accurate geometrical recovery were achieved using the ordered subset expectation maximization reconstruction algorithm with time-of-flight (TOF) and point-spread function (PSF) information. For this algorithm, reasonably accurate (better than 5%) and precise (uncertainty of the mean activity below 10%) imaging can be provided down to 80,000 true coincidences at 96% RF. Image noise and geometrical fidelity are generally improved for fewer iterations. The main limitation for PET-based treatment monitoring has been identified in the small number of true coincidences, rather than the high intrinsic random background. Application of the optimized reconstruction scheme to patient data-sets results in a 25% - 50% reduced image noise at a comparable activity quantification accuracy and an improved geometrical performance with respect to the formerly used reconstruction scheme at HIT, adopted from nuclear medicine applications. CONCLUSIONS: Under the poor statistical conditions in PET based treatment monitoring, improved results can be achieved by considering PSF and TOF information during image reconstruction and by applying less iterations than in conventional nuclear medicine imaging. Geometrical fidelity and image noise are mainly limited by the low number of true coincidences, not the high LSO related random background. The retrieved results might also impact other emerging PET applications at low counting statistics. PMID- 26133599 TI - Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty. AB - PURPOSE: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. METHODS: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goals to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. RESULTS: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. CONCLUSIONS: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality. PMID- 26133600 TI - Speckle contrast diffuse correlation tomography of complex turbid medium flow. AB - PURPOSE: Developed herein is a three-dimensional (3D) flow contrast imaging system leveraging advancements in the extension of laser speckle contrast imaging theories to deep tissues along with our recently developed finite-element diffuse correlation tomography (DCT) reconstruction scheme. This technique, termed speckle contrast diffuse correlation tomography (scDCT), enables incorporation of complex optical property heterogeneities and sample boundaries. When combined with a reflectance-based design, this system facilitates a rapid segue into flow contrast imaging of larger, in vivo applications such as humans. METHODS: A highly sensitive CCD camera was integrated into a reflectance-based optical system. Four long-coherence laser source positions were coupled to an optical switch for sequencing of tomographic data acquisition providing multiple projections through the sample. This system was investigated through incorporation of liquid and solid tissue-like phantoms exhibiting optical properties and flow characteristics typical of human tissues. Computer simulations were also performed for comparisons. A uniquely encountered smear correction algorithm was employed to correct point-source illumination contributions during image capture with the frame-transfer CCD and reflectance setup. RESULTS: Measurements with scDCT on a homogeneous liquid phantom showed that speckle contrast-based deep flow indices were within 12% of those from standard DCT. Inclusion of a solid phantom submerged below the liquid phantom surface allowed for heterogeneity detection and validation. The heterogeneity was identified successfully by reconstructed 3D flow contrast tomography with scDCT. The heterogeneity center and dimensions and averaged relative flow (within 3%) and localization were in agreement with actuality and computer simulations, respectively. CONCLUSIONS: A custom cost-effective CCD-based reflectance 3D flow imaging system demonstrated rapid acquisition of dense boundary data and, with further studies, a high potential for translatability to real tissues with arbitrary boundaries. A requisite correction was also found for measurements in the fashion of scDCT to recover accurate speckle contrast of deep tissues. PMID- 26133601 TI - Technical Note: Convergence analysis of a polyenergetic SART algorithm. AB - PURPOSE: The authors analyze a recently proposed polyenergetic version of the simultaneous algebraic reconstruction technique (SART). This algorithm, denoted polyenergetic SART (pSART), replaces the monoenergetic forward projection operation used by SART with a postlog, polyenergetic forward projection, while leaving the rest of the algorithm unchanged. While the proposed algorithm provides good results empirically, convergence of the algorithm was not established mathematically in the original paper. METHODS: The authors analyze pSART as a nonlinear fixed point iteration by explicitly computing the Jacobian of the iteration. A necessary condition for convergence is that the spectral radius of the Jacobian, evaluated at the fixed point, is less than one. A short proof of convergence for SART is also provided as a basis for comparison. RESULTS: The authors show that the pSART algorithm is not guaranteed to converge, in general. The Jacobian of the iteration depends on several factors, including the system matrix and how one models the energy dependence of the linear attenuation coefficient. The authors provide a simple numerical example that shows that the spectral radius of the Jacobian matrix is not guaranteed to be less than one. A second set of numerical experiments using realistic CT system matrices, however, indicates that conditions for convergence are likely to be satisfied in practice. CONCLUSIONS: Although pSART is not mathematically guaranteed to converge, their numerical experiments indicate that it will tend to converge at roughly the same rate as SART for system matrices of the type encountered in CT imaging. Thus, the authors conclude that the algorithm is still a useful method for reconstruction of polyenergetic CT data. PMID- 26133602 TI - Tracking fuzzy borders using geodesic curves with application to liver segmentation on planning CT. AB - PURPOSE: This work aims to develop a robust and efficient method to track the fuzzy borders between liver and the abutted organs where automatic liver segmentation usually suffers, and to investigate its applications in automatic liver segmentation on noncontrast-enhanced planning computed tomography (CT) images. METHODS: In order to track the fuzzy liver-chestwall and liver-heart borders where oversegmentation is often found, a starting point and an ending point were first identified on the coronal view images; the fuzzy border was then determined as a geodesic curve constructed by minimizing the gradient-weighted path length between these two points near the fuzzy border. The minimization of path length was numerically solved by fast-marching method. The resultant fuzzy borders were incorporated into the authors' automatic segmentation scheme, in which the liver was initially estimated by a patient-specific adaptive thresholding and then refined by a geodesic active contour model. By using planning CT images of 15 liver patients treated with stereotactic body radiation therapy, the liver contours extracted by the proposed computerized scheme were compared with those manually delineated by a radiation oncologist. RESULTS: The proposed automatic liver segmentation method yielded an average Dice similarity coefficient of 0.930 +/- 0.015, whereas it was 0.912 +/- 0.020 if the fuzzy border tracking was not used. The application of fuzzy border tracking was found to significantly improve the segmentation performance. The mean liver volume obtained by the proposed method was 1727 cm(3), whereas it was 1719 cm(3) for manual-outlined volumes. The computer-generated liver volumes achieved excellent agreement with manual-outlined volumes with correlation coefficient of 0.98. CONCLUSIONS: The proposed method was shown to provide accurate segmentation for liver in the planning CT images where contrast agent is not applied. The authors' results also clearly demonstrated that the application of tracking the fuzzy borders could significantly reduce contour leakage during active contour evolution. PMID- 26133603 TI - Technical Note: Nanometric organic photovoltaic thin film detectors for dose monitoring in diagnostic x-ray imaging. AB - PURPOSE: To fabricate organic photovoltaic (OPV) cells with nanometric active layers sensitive to ionizing radiation and measure their dosimetric characteristics in clinical x-ray beams in the diagnostic tube potential range of 60-150 kVp. METHODS: Experiments were designed to optimize the detector's x-ray response and find the best parameter combination by changing the active layer thickness and the area of the electrode. The OPV cell consisted of poly (3 hexylthiophene-2,5-diyl): [6,6]-phenyl C61 butyric acid methyl ester photoactive donor and acceptor semiconducting organic materials sandwiched between an aluminum electrode as an anode and an indium tin oxide electrode as a cathode. The authors measured the radiation-induced electric current at zero bias voltage in all fabricated OPV cells. RESULTS: The net OPV current as a function of beam potential (kVp) was proportional to kVp(-0.5) when normalized to x-ray tube output, which varies with kVp. Of the tested configurations, the best combination of parameters was 270 nm active layer thicknesses with 0.7 cm(2) electrode area, which provided the highest signal per electrode area. For this cell, the measured current ranged from approximately 0.7 to 2.4 nA/cm(2) for 60-150 kVp, corresponding to about 0.09 nA-0.06 nA/mGy air kerma, respectively. When compared to commercial amorphous silicon thin film photovoltaic cells irradiated under the same conditions, this represents 2.5 times greater sensitivity. An additional 40% signal enhancement was observed when a 1 mm layer of plastic scintillator was attached to the cells' beam-facing side. CONCLUSIONS: Since both OPVs can be produced as flexible devices and they do not require external bias voltage, they open the possibility for use as thin film in vivo detectors for dose monitoring in diagnostic x-ray imaging. PMID- 26133604 TI - Comparison of breathing gated CT images generated using a 5DCT technique and a commercial clinical protocol in a porcine model. AB - PURPOSE: To demonstrate that a "5DCT" technique which utilizes fast helical acquisition yields the same respiratory-gated images as a commercial technique for regular, mechanically produced breathing cycles. METHODS: Respiratory-gated images of an anesthetized, mechanically ventilated pig were generated using a Siemens low-pitch helical protocol and 5DCT for a range of breathing rates and amplitudes and with standard and low dose imaging protocols. 5DCT reconstructions were independently evaluated by measuring the distances between tissue positions predicted by a 5D motion model and those measured using deformable registration, as well by reconstructing the originally acquired scans. Discrepancies between the 5DCT and commercial reconstructions were measured using landmark correspondences. RESULTS: The mean distance between model predicted tissue positions and deformably registered tissue positions over the nine datasets was 0.65 +/- 0.28 mm. Reconstructions of the original scans were on average accurate to 0.78 +/- 0.57 mm. Mean landmark displacement between the commercial and 5DCT images was 1.76 +/- 1.25 mm while the maximum lung tissue motion over the breathing cycle had a mean value of 27.2 +/- 4.6 mm. An image composed of the average of 30 deformably registered images acquired with a low dose protocol had 6 HU image noise (single standard deviation) in the heart versus 31 HU for the commercial images. CONCLUSIONS: An end to end evaluation of the 5DCT technique was conducted through landmark based comparison to breathing gated images acquired with a commercial protocol under highly regular ventilation. The techniques were found to agree to within 2 mm for most respiratory phases and most points in the lung. PMID- 26133605 TI - Automatic segmentation method for bone and blood vessel in murine hindlimb. AB - PURPOSE: The goal of this paper is to address three problems existing in vessel extraction of murine hindlimb. First, the bone can hardly be separated from blood vessels because the intensity of contrast enhanced blood vessels is similar to that of bones. Second, as an automatic blood vessel segmentation method, the vesselness method is sensitive to sharp boundaries, resulting in false positive effect in nonvascular regions. Finally, thin blood vessels are always broken after segmentation because of the low signal-to-noise ratio. METHODS: The proposed automatic segmentation method for bone and blood vessel in this paper includes three important modules. (1) To eliminate the interference of bones on the segmentation of blood vessels, the authors employ split Bregman method to segment bones in the first place. (2) The authors propose an edge extension strategy to cope with the false positive effect of the vesselness method on the sharp boundaries of hindlimb after the removal of bones. Then, the authors segment the blood vessels using the vesselness method combined with multiscale bi Gaussian filtering. (3) The authors reconnect the broken blood vessels after segmentation based on centerline and morphological dilation. RESULTS: The bones' segmentation from the murine hindlimbs was conducted using the split Bregman, manual, and thresholding methods, respectively. Compared with the thresholding method, the split Bregman method could finely segment the bones from blood vessels, and the results were comparable to that of manual segmentation. After removing bones, the vesselness method combined with the bi-Gaussian filtering with and without edge extension was performed. The vesselness results with the edge extension strategy could effectively eliminate the false positive effect on sharp boundaries in nonvascular regions. Some of the blood vessels segmented by thresholding from the vesselness results were disconnected. Thus, the authors employed the vascular connection method based on centerline and morphological dilation to connect the broken blood vessels. Compared with the vascular connection utilizing the spatial-variant and -invariant morphological closing methods, the proposed vascular connection method reconnected the broken blood vessels and meanwhile maintained the nonbroken ones unchanged. CONCLUSIONS: Our proposed method is suitable for the segmentation of bones and blood vessels in murine hindlimbs. For the segmentation of bones, the split Bregman method improves the distinguishability between bones and blood vessels, since both the intensity information and the geometrical size are exploited. For the segmentation of blood vessels, vesselness method with the edge extension strategy eliminates the false positive effect on the nonvascular sharp boundaries. After segmentation, the proposed vascular connection method based on centerline and morphological dilation can reconnect the broken blood vessels without affecting the nonbroken ones. PMID- 26133606 TI - A prototype, glassless densitometer traceable to primary optical standards for quantitative radiochromic film dosimetry. AB - PURPOSE: To evaluate a prototype densitometer traceable to primary optical standards and compare its performance to an EPSON Expression((r)) 10000XL flatbed scanner (the Epson) for quantitative radiochromic film (RCF) dosimetry. METHODS: A prototype traceable laser densitometry system (LDS) was developed to mitigate common film scanning artifacts, such as positional scan dependence and high noise in low-dose regions, by performing point-based measurements of RCF suspended in free-space using coherent light. The LDS and the Epson optical absorbance scales were calibrated up to 3 AU, using reference materials calibrated at a primary standards laboratory and a scanner calibration factor (SCF). Calibrated optical density (OD) was determined for 96 Gafchromic((r)) EBT3 film segments before and after irradiation to one of 16 dose levels between 0 and 10 Gy, exposed to (60)Co in a polymethyl-methacrylate (PMMA) phantom. The sensitivity was determined at each dose level and at two rotationally orthogonal readout orientations to obtain the sensitometric response of each RCF dosimetry system. LDS rotational scanning dependence was measured at nine angles between 0 degrees and 180 degrees , due to the expected interference between coherent light and polarizing EBT3 material. The response curves were fit to the analytic functions predicted by two physical response models: the two-parameter single-hit model and the four-parameter percolation model. RESULTS: The LDS and the Epson absorbance measurements were linear to primary optical standards to within 0.2% and 0.3% up to 2 and 1 AU, respectively. At higher densities, the LDS had an over-response (2.5% at 3 AU) and the Epson an under-response (3.1% and 9.8% at 2 and 3 AU, respectively). The LDS and the Epson SCF over the applicable range were 0.968% +/- 0.2% and 1.561% +/- 0.3%, respectively. The positional scan dependence was evaluated on each digitizer and shown to be mitigated on the LDS, as compared to the Epson. Maximum EBT3 rotational dependence was found to have a strong dependence on dose (0.1% and 34% at 30 mGy and 5 Gy, respectively). The preferred EBT3 polymerization axis angle was constant within experimental uncertainties. In its most sensitive orientation, the LDS-measured EBT3 sensitivity was 7.13 * 10(-4) +/- 9.2 * 10(-6) AU/mGy, which represented a 4.5 fold increase over the Epson of 1.58 * 10(-4) +/- 9.8 * 10(-6) AU/mGy. To first order approximations, EBT3 response was linear up to 500 mGy to within 0.80% and to within 7.5% for the most sensitive LDS and the Epson orientations, respectively. The corresponding single-hit and percolation model relative residual norms were 0.082 and 0.074 for LDS as compared to 0.29 and 0.18 for the Epson, which represented a significant increase in LDS-measured agreement with the simple physical model. Less sensitive LDS and the Epson orientations showed a marked decrease in the physical model agreement, which suggested that suboptimal readout device characteristics may be the origin of the complex sensitometric functional forms currently required for accurate RCF dosimetry. CONCLUSIONS: The prototype densitometer was shown to be superior to a conventional scanner for quantitative RCF dosimetry based on physical models of film response. The Epson was shown to be a reliable tool for routine RCF dosimetry in a clinical setting, yet calibration to primary optical standards did not mitigate the necessity for complex, empirical functional form fitting. PMID- 26133607 TI - Micrometer-resolved film dosimetry using a microscope in microbeam radiation therapy. AB - PURPOSE: Microbeam radiation therapy (MRT) is a still preclinical tumor therapy approach that uses arrays of a few tens of micrometer wide parallel beams separated by a few 100 MUm. The production, measurement, and planning of such radiation fields are a challenge up to now. Here, the authors investigate the feasibility of radiochromic film dosimetry in combination with a microscopic readout as a tool to validate peak and valley doses in MRT, which is an important requirement for a future clinical application of the therapy. METHODS: Gafchromic((r)) HD-810 and HD-V2 films are exposed to MRT fields at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF) and are afterward scanned with a microscope. The measured dose is compared with Monte Carlo calculations. Image analysis tools and film handling protocols are developed that allow accurate and reproducible dosimetry. The performance of HD 810 and HD-V2 films is compared and a detailed analysis of the resolution, noise, and energy dependence is carried out. Measurement uncertainties are identified and analyzed. RESULTS: The dose was measured with a resolution of 5 * 1000 MUm(2) and an accuracy of 5% in the peak and between 10% and 15% in the valley region. As main causes for dosimetry uncertainties, statistical noise, film inhomogeneities, and calibration errors were identified. Calibration errors strongly increase at low doses and exceeded 3% for doses below 50 and 70 Gy for HD-V2 and HD-810 films, respectively. While the grain size of both film types is approximately 2 MUm, the statistical noise in HD-V2 is much higher than in HD-810 films. However, HD-810 films show a higher energy dependence at low photon energies. CONCLUSIONS: Both film types are appropriate for dosimetry in MRT and the microscope is superior to the microdensitometer used before at the ESRF with respect to resolution and reproducibility. However, a very careful analysis of the image data is required. Dosimetry at low photon energies should be performed with great caution due to the energy sensitivity of the films. In this respect, HD-V2 films showed to have an advantage over HD-810 films. However, HD-810 films have a lower statistical noise level. When a higher resolution is required, e.g., for the dosimetry of pencil beam irradiations, noise may render HD-V2 films inapplicable. PMID- 26133608 TI - Deterministic absorbed dose estimation in computed tomography using a discrete ordinates method. AB - PURPOSE: Organ dose estimation for a patient undergoing computed tomography (CT) scanning is very important. Although Monte Carlo methods are considered gold standard in patient dose estimation, the computation time required is formidable for routine clinical calculations. Here, the authors instigate a deterministic method for estimating an absorbed dose more efficiently. METHODS: Compared with current Monte Carlo methods, a more efficient approach to estimating the absorbed dose is to solve the linear Boltzmann equation numerically. In this study, an axial CT scan was modeled with a software package, Denovo, which solved the linear Boltzmann equation using the discrete ordinates method. The CT scanning configuration included 16 x-ray source positions, beam collimators, flat filters, and bowtie filters. The phantom was the standard 32 cm CT dose index (CTDI) phantom. Four different Denovo simulations were performed with different simulation parameters, including the number of quadrature sets and the order of Legendre polynomial expansions. A Monte Carlo simulation was also performed for benchmarking the Denovo simulations. A quantitative comparison was made of the simulation results obtained by the Denovo and the Monte Carlo methods. RESULTS: The difference in the simulation results of the discrete ordinates method and those of the Monte Carlo methods was found to be small, with a root-mean-square difference of around 2.4%. It was found that the discrete ordinates method, with a higher order of Legendre polynomial expansions, underestimated the absorbed dose near the center of the phantom (i.e., low dose region). Simulations of the quadrature set 8 and the first order of the Legendre polynomial expansions proved to be the most efficient computation method in the authors' study. The single thread computation time of the deterministic simulation of the quadrature set 8 and the first order of the Legendre polynomial expansions was 21 min on a personal computer. CONCLUSIONS: The simulation results showed that the deterministic method can be effectively used to estimate the absorbed dose in a CTDI phantom. The accuracy of the discrete ordinates method was close to that of a Monte Carlo simulation, and the primary benefit of the discrete ordinates method lies in its rapid computation speed. It is expected that further optimization of this method in routine clinical CT dose estimation will improve its accuracy and speed. PMID- 26133609 TI - Technical Note: Relation between dual-energy subtraction of CT images for electron density calibration and virtual monochromatic imaging. AB - PURPOSE: For accurate tissue inhomogeneity correction in radiotherapy treatment planning, the author previously proposed a simple conversion of the energy subtracted computed tomography (CT) number to an electron density (DeltaHU-rhoe conversion), which provides a single linear relationship between DeltaHU and rhoe over a wide rhoe range. The purpose of the present study was to reveal the relation between the DeltaHU image for rhoe calibration and a virtually monochromatic CT image by performing numerical analyses based on the basis material decomposition in dual-energy CT. METHODS: The author determined the weighting factor, alpha0, of the DeltaHU-rhoe conversion through numerical analyses of the International Commission on Radiation Units and Measurements Report-46 human body tissues using their attenuation coefficients and given rhoe values. Another weighting factor, alpha(E), for synthesizing a virtual monochromatic CT image from high- and low-kV CT images, was also calculated in the energy range of 0.03 < E < 5 MeV, assuming that cortical bone and water were the basis materials. The mass attenuation coefficients for these materials were obtained using the xcom photon cross sections database. The effective x-ray energies used to calculate the attenuation were chosen to imitate a dual-source CT scanner operated at 80-140 and 100-140 kV/Sn. RESULTS: The determined alpha0 values were 0.455 for 80-140 kV/Sn and 0.743 for 100-140 kV/Sn. These values coincided almost perfectly with the respective maximal points of the calculated alpha(E) curves located at approximately 1 MeV, in which the photon-matter interaction in human body tissues is exclusively the incoherent (Compton) scattering. CONCLUSIONS: The DeltaHU image could be regarded substantially as a CT image acquired with monoenergetic 1-MeV photons, which provides a linear relationship between CT numbers and electron densities. PMID- 26133611 TI - Determining the in vivo elastic properties of dermis layer of human skin using the supersonic shear imaging technique and inverse analysis. AB - PURPOSE: Human skin consists of several layers including epidermis, dermis, and hypodermis. The determination of the in vivo mechanical properties of an individual skin layer represents a great challenge to date. In this study, the authors explore the use of the supersonic shear imaging (SSI) technique and inverse analysis to determine the in vivo elastic properties of the dermis layer of human skin. METHODS: The measurements are conducted on the volar forearms and dorsal forearms of 18 healthy volunteers (nine females and nine males) using the SSI technique that gives the velocities of the shear wave generated by the acoustic force. Finite element analysis is carried out to simulate the propagation of the shear wave in the multilayer soft media and the results are used to interpret the experimental data and deduce the shear modulus of the dermis layer. RESULTS: The shear moduli of the skin dermis layer obtained for the 18 healthy volunteers exhibit significant anisotropy. A standard statistical analysis demonstrates the differences between sexes. CONCLUSIONS: This study demonstrates that the SSI technique together with the inverse analysis represents a useful tool to characterize the in vivo elastic properties of human skin. PMID- 26133610 TI - Quantitative single-particle digital autoradiography with alpha-particle emitters for targeted radionuclide therapy using the iQID camera. AB - PURPOSE: Alpha-emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50-80 MUm), causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with alpha emitters may thus inactivate targeted cells with minimal radiation damage to surrounding tissues. Tools are needed to visualize and quantify the radioactivity distribution and absorbed doses to targeted and nontargeted cells for accurate dosimetry of all treatment regimens utilizing alpha particles, including RIT and others (e.g., Ra-223), especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, the ionizing-radiation quantum imaging detector (iQID) camera, for use in alpha-RIT experiments. METHODS: The iQID camera is a scintillator-based radiation detection system that images and identifies charged-particle and gamma-ray/x-ray emissions spatially and temporally on an event-by-event basis. It employs CCD CMOS cameras and high-performance computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, the authors evaluated its characteristics for alpha-particle imaging, including measurements of intrinsic detector spatial resolutions and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine 211 ((211)At) activity distributions in cryosections of murine and canine tissue samples. RESULTS: The highest spatial resolution was measured at ~20 MUm full width at half maximum and the alpha-particle background was measured at a rate as low as (2.6 +/- 0.5) * 10(-4) cpm/cm(2) (40 mm diameter detector area). Simultaneous imaging of multiple tissue sections was performed using a large-area iQID configuration (o 11.5 cm). Estimation of the (211)At activity distribution was demonstrated at mBq/MUg-levels. CONCLUSIONS: Single-particle digital autoradiography of alpha emitters has advantages over traditional film-based autoradiographic techniques that use phosphor screens, in terms of spatial resolution, sensitivity, and activity quantification capability. The system features and characterization results presented in this study show that the iQID is a promising technology for microdosimetry, because it provides necessary information for interpreting alpha-RIT outcomes and for predicting the therapeutic efficacy of cell-targeted approaches using alpha emitters. PMID- 26133612 TI - Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data. AB - PURPOSE: Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. METHODS: The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. RESULTS: The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power-law descriptions of the phantom images were in general agreement with real human images. The Singlet approach offered more realistic contrast as compared to the Doublet approach, but at the expense of air bubbles and air pockets that formed during the filling process. CONCLUSIONS: The presented physical breast phantoms and their matching virtual breast phantoms offer realistic breast anatomy, patient variability, and ease of use, making them a potential candidate for performing both system quality control testing and virtual clinical trials. PMID- 26133614 TI - A framework for the correction of slow physiological drifts during MR-guided HIFU therapies: Proof of concept. AB - PURPOSE: While respiratory motion compensation for magnetic resonance (MR)-guided high intensity focused ultrasound (HIFU) interventions has been extensively studied, the influence of slow physiological motion due to, for example, peristaltic activity, has so far been largely neglected. During lengthy interventions, the magnitude of the latter can exceed acceptable therapeutic margins. The goal of the present study is to exploit the episodic workflow of these therapies to implement a motion correction strategy for slow varying drifts of the target area and organs at risk over the entire duration of the intervention. METHODS: The therapeutic workflow of a MR-guided HIFU intervention is in practice often episodic: Bursts of energy delivery are interleaved with periods of inactivity, allowing the effects of the beam on healthy tissues to recede and/or during which the plan of the intervention is reoptimized. These periods usually last for at least several minutes. It is at this time scale that organ drifts due to slow physiological motion become significant. In order to capture these drifts, the authors propose the integration of 3D MR scans in the therapy workflow during the inactivity intervals. Displacements were estimated using an optical flow algorithm applied on the 3D acquired images. A preliminary study was conducted on ten healthy volunteers. For each volunteer, 3D MR images of the abdomen were acquired at regular intervals of 10 min over a total duration of 80 min. Motion analysis was restricted to the liver and kidneys. For validating the compatibility of the proposed motion correction strategy with the workflow of a MR-guided HIFU therapy, an in vivo experiment on a porcine liver was conducted. A volumetric HIFU ablation was completed over a time span of 2 h. A 3D image was acquired before the first sonication, as well as after each sonication. RESULTS: Following the volunteer study, drifts larger than 8 mm for the liver and 5 mm for the kidneys prove that slow physiological motion can exceed acceptable therapeutic margins. In the animal experiment, motion tracking revealed an initial shift of up to 4 mm during the first 10 min and a subsequent continuous shift of ~2 mm/h until the end of the intervention. This leads to a continuously increasing mismatch of the initial shot planning, the thermal dose measurements, and the true underlying anatomy. The estimated displacements allowed correcting the planned sonication cell cluster positions to the true target position, as well as the thermal dose estimates during the entire intervention and to correct the nonperfused volume measurement. A spatial coherence of all three is particularly important to assure a confluent ablation volume and to prevent remaining islets of viable malignant tissue. CONCLUSIONS: This study proposes a motion correction strategy for displacements resulting from slowly varying physiological motion that might occur during a MR-guided HIFU intervention. The authors have shown that such drifts can lead to a misalignment between interventional planning, energy delivery, and therapeutic validation. The presented volunteer study and in vivo experiment demonstrate both the relevance of the problem for HIFU therapies and the compatibility of the proposed motion compensation framework with the workflow of a HIFU intervention under clinical conditions. PMID- 26133613 TI - Optical cone beam tomography of Cherenkov-mediated signals for fast 3D dosimetry of x-ray photon beams in water. AB - PURPOSE: To test the use of a three-dimensional (3D) optical cone beam computed tomography reconstruction algorithm, for estimation of the imparted 3D dose distribution from megavoltage photon beams in a water tank for quality assurance, by imaging the induced Cherenkov-excited fluorescence (CEF). METHODS: An intensified charge-coupled device coupled to a standard nontelecentric camera lens was used to tomographically acquire two-dimensional (2D) projection images of CEF from a complex multileaf collimator (MLC) shaped 6 MV linear accelerator x ray photon beam operating at a dose rate of 600 MU/min. The resulting projections were used to reconstruct the 3D CEF light distribution, a potential surrogate of imparted dose, using a Feldkamp-Davis-Kress cone beam back reconstruction algorithm. Finally, the reconstructed light distributions were compared to the expected dose values from one-dimensional diode scans, 2D film measurements, and the 3D distribution generated from the clinical Varian ECLIPSE treatment planning system using a gamma index analysis. A Monte Carlo derived correction was applied to the Cherenkov reconstructions to account for beam hardening artifacts. RESULTS: 3D light volumes were successfully reconstructed over a 400 * 400 * 350 mm(3) volume at a resolution of 1 mm. The Cherenkov reconstructions showed agreement with all comparative methods and were also able to recover both inter- and intra-MLC leaf leakage. Based upon a 3%/3 mm criterion, the experimental Cherenkov light measurements showed an 83%-99% pass fraction depending on the chosen threshold dose. CONCLUSIONS: The results from this study demonstrate the use of optical cone beam computed tomography using CEF for the profiling of the imparted dose distribution from large area megavoltage photon beams in water. PMID- 26133615 TI - Parenchymal texture analysis in digital mammography: A fully automated pipeline for breast cancer risk assessment. AB - PURPOSE: Mammographic percent density (PD%) is known to be a strong risk factor for breast cancer. Recent studies also suggest that parenchymal texture features, which are more granular descriptors of the parenchymal pattern, can provide additional information about breast cancer risk. To date, most studies have measured mammographic texture within selected regions of interest (ROIs) in the breast, which cannot adequately capture the complexity of the parenchymal pattern throughout the whole breast. To better characterize patterns of the parenchymal tissue, the authors have developed a fully automated software pipeline based on a novel lattice-based strategy to extract a range of parenchymal texture features from the entire breast region. METHODS: Digital mammograms from 106 cases with 318 age-matched controls were retrospectively analyzed. The lattice-based approach is based on a regular grid virtually overlaid on each mammographic image. Texture features are computed from the intersection (i.e., lattice) points of the grid lines within the breast, using a local window centered at each lattice point. Using this strategy, a range of statistical (gray-level histogram, co-occurrence, and run-length) and structural (edge-enhancing, local binary pattern, and fractal dimension) features are extracted. To cover the entire breast, the size of the local window for feature extraction is set equal to the lattice grid spacing and optimized experimentally by evaluating different windows sizes. The association between their lattice-based texture features and breast cancer was evaluated using logistic regression with leave-one-out cross validation and further compared to that of breast PD% and commonly used single ROI texture features extracted from the retroareolar or the central breast region. Classification performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). DeLong's test was used to compare the different ROCs in terms of AUC performance. RESULTS: The average univariate performance of the lattice-based features is higher when extracted from smaller than larger window sizes. While not every individual texture feature is superior to breast PD% (AUC: 0.59, STD: 0.03), their combination in multivariate analysis has significantly better performance (AUC: 0.85, STD: 0.02, p < 0.001). The lattice-based texture features also outperform the single-ROI texture features when extracted from the retroareolar or the central breast region (AUC: 0.60-0.74, STD: 0.03). Adding breast PD% does not make a significant performance improvement to the lattice-based texture features or the single-ROI features (p > 0.05). CONCLUSIONS: The proposed lattice-based strategy for mammographic texture analysis enables to characterize the parenchymal pattern over the entire breast. As such, these features provide richer information compared to currently used descriptors and may ultimately improve breast cancer risk assessment. Larger studies are warranted to validate these findings and also compare to standard demographic and reproductive risk factors. PMID- 26133616 TI - Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina. AB - PURPOSE: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (l) 4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. METHODS: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. RESULTS: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 +/- 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 +/- 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. CONCLUSIONS: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life. PMID- 26133617 TI - Hierarchical and symmetric infant image registration by robust longitudinal example-guided correspondence detection. AB - PURPOSE: To investigate anatomical differences across individual subjects, or longitudinal changes in early brain development, it is important to perform accurate image registration. However, due to fast brain development and dynamic tissue appearance changes, it is very difficult to align infant brain images acquired from birth to 1-yr-old. METHODS: To solve this challenging problem, a novel image registration method is proposed to align two infant brain images, regardless of age at acquisition. The main idea is to utilize the growth trajectories, or spatial-temporal correspondences, learned from a set of longitudinal training images, for guiding the registration of two different time point images with different image appearances. Specifically, in the training stage, an intrinsic growth trajectory is first estimated for each training subject using the longitudinal images. To register two new infant images with potentially a large age gap, the corresponding images patches between each new image and its respective training images with similar age are identified. Finally, the registration between the two new images can be assisted by the learned growth trajectories from one time point to another time point that have been established in the training stage. To further improve registration accuracy, the proposed method is combined with a hierarchical and symmetric registration framework that can iteratively add new key points in both images to steer the estimation of the deformation between the two infant brain images under registration. RESULTS: To evaluate image registration accuracy, the proposed method is used to align 24 infant subjects at five different time points (2-week old, 3-month-old, 6-month-old, 9-month-old, and 12-month-old). Compared to the state-of-the-art methods, the proposed method demonstrated superior registration performance. CONCLUSIONS: The proposed method addresses the difficulties in the infant brain registration and produces better results compared to existing state of-the-art registration methods. PMID- 26133618 TI - Development of an accurate EPID-based output measurement and dosimetric verification tool for electron beam therapy. AB - PURPOSE: To develop an efficient and robust tool for output measurement and absolute dose verification of electron beam therapy by using a high spatial resolution and high frame-rate amorphous silicon flat panel electronic portal imaging device (EPID). METHODS: The dosimetric characteristics of the EPID, including saturation, linearity, and ghosting effect, were first investigated on a Varian Clinac 21EX accelerator. The response kernels of the individual pixels of the EPID to all available electron energies (6, 9, 12, 16, and 20 MeV) were calculated by using Monte Carlo (MC) simulations, which formed the basis to deconvolve an EPID raw images to the incident electron fluence map. The two dimensional (2D) dose distribution at reference depths in water was obtained by using the constructed fluence map with a MC simulated pencil beam kernel with consideration of the geometric and structural information of the EPID. Output factor measurements were carried out with the EPID at a nominal source-surface distance of 100 cm for 2 * 2, 3 * 3, 6 * 6, 10 * 10, and 15 * 15 cm(2) fields for all available electron energies, and the results were compared with that measured in a solid water phantom using film and a Farmer-type ion chamber. The dose distributions at a reference depth specific to each energy and the flatness and symmetry of the 10 * 10 cm(2) electron beam were also measured using EPID, and the results were compared with ion chamber array and water scan measurements. Finally, three patient cases with various field sizes and irregular cutout shapes were also investigated. RESULTS: EPID-measured dose changed linearly with the monitor units and showed little ghosting effect for dose rate up to 600 MU/min. The flatness and symmetry measured with the EPID were found to be consistent with ion chamber array and water scan measurements. The EPID-measured output factors for standard square fields of 2 * 2, 3 * 3, 6 * 6, 10 * 10, 15 * 15 cm(2) agreed with film and ion chamber measurements. The average discrepancy between EPID and ion chamber/film measurements was 0.81% +/- 0.60% (SD) and 1.34% +/- 0.75%, respectively. For the three clinical cases, the difference in output between the EPID- and ion chamber array measured values was found to be 1.13% +/- 0.11%, 0.54% +/- 0.10%, and 0.74% +/- 0.11%, respectively. Furthermore, the gamma-index analysis showed an excellent agreement between the EPID- and ion chamber array measured dose distributions: 100% of the pixels passed the criteria of 3%/3 mm. When the gamma-index was set to be 2%/2 mm, the pass rate was found to be 99.0% +/- 0.07%, 98.2% +/- 0.14%, and 100% for the three cases. CONCLUSIONS: The EPID dosimetry system developed in this work provides an accurate and reliable tool for routine output measurement and dosimetric verification of electron beam therapy. Coupled with its portability and ease of use, the proposed system promises to replace the current film-based approach for fast and reliable assessment of small and irregular electron field dosimetry. PMID- 26133619 TI - Experimental depth dose curves of a 67.5 MeV proton beam for benchmarking and validation of Monte Carlo simulation. AB - PURPOSE: To measure depth dose curves for a 67.5 +/- 0.1 MeV proton beam for benchmarking and validation of Monte Carlo simulation. METHODS: Depth dose curves were measured in 2 beam lines. Protons in the raw beam line traversed a Ta scattering foil, 0.1016 or 0.381 mm thick, a secondary emission monitor comprised of thin Al foils, and a thin Kapton exit window. The beam energy and peak width and the composition and density of material traversed by the beam were known with sufficient accuracy to permit benchmark quality measurements. Diodes for charged particle dosimetry from two different manufacturers were used to scan the depth dose curves with 0.003 mm depth reproducibility in a water tank placed 300 mm from the exit window. Depth in water was determined with an uncertainty of 0.15 mm, including the uncertainty in the water equivalent depth of the sensitive volume of the detector. Parallel-plate chambers were used to verify the accuracy of the shape of the Bragg peak and the peak-to-plateau ratio measured with the diodes. The uncertainty in the measured peak-to-plateau ratio was 4%. Depth dose curves were also measured with a diode for a Bragg curve and treatment beam spread out Bragg peak (SOBP) on the beam line used for eye treatment. The measurements were compared to Monte Carlo simulation done with geant4 using topas. RESULTS: The 80% dose at the distal side of the Bragg peak for the thinner foil was at 37.47 +/- 0.11 mm (average of measurement with diodes from two different manufacturers), compared to the simulated value of 37.20 mm. The 80% dose for the thicker foil was at 35.08 +/- 0.15 mm, compared to the simulated value of 34.90 mm. The measured peak-to-plateau ratio was within one standard deviation experimental uncertainty of the simulated result for the thinnest foil and two standard deviations for the thickest foil. It was necessary to include the collimation in the simulation, which had a more pronounced effect on the peak to-plateau ratio for the thicker foil. The treatment beam, being unfocussed, had a broader Bragg peak than the raw beam. A 1.3 +/- 0.1 MeV FWHM peak width in the energy distribution was used in the simulation to match the Bragg peak width. An additional 1.3-2.24 mm of water in the water column was required over the nominal values to match the measured depth penetration. CONCLUSIONS: The proton Bragg curve measured for the 0.1016 mm thick Ta foil provided the most accurate benchmark, having a low contribution of proton scatter from upstream of the water tank. The accuracy was 0.15% in measured beam energy and 0.3% in measured depth penetration at the Bragg peak. The depth of the distal edge of the Bragg peak in the simulation fell short of measurement, suggesting that the mean ionization potential of water is 2-5 eV higher than the 78 eV used in the stopping power calculation for the simulation. The eye treatment beam line depth dose curves provide validation of Monte Carlo simulation of a Bragg curve and SOBP with 4%/2 mm accuracy. PMID- 26133620 TI - Characterization of XR-RV3 GafChromic((r)) films in standard laboratory and in clinical conditions and means to evaluate uncertainties and reduce errors. AB - PURPOSE: To investigate the optimal use of XR-RV3 GafChromic((r)) films to assess patient skin dose in interventional radiology while addressing the means to reduce uncertainties in dose assessment. METHODS: XR-Type R GafChromic films have been shown to represent the most efficient and suitable solution to determine patient skin dose in interventional procedures. As film dosimetry can be associated with high uncertainty, this paper presents the EURADOS WG 12 initiative to carry out a comprehensive study of film characteristics with a multisite approach. The considered sources of uncertainties include scanner, film, and fitting-related errors. The work focused on studying film behavior with clinical high-dose-rate pulsed beams (previously unavailable in the literature) together with reference standard laboratory beams. RESULTS: First, the performance analysis of six different scanner models has shown that scan uniformity perpendicular to the lamp motion axis and that long term stability are the main sources of scanner-related uncertainties. These could induce errors of up to 7% on the film readings unless regularly checked and corrected. Typically, scan uniformity correction matrices and reading normalization to the scanner specific and daily background reading should be done. In addition, the analysis on multiple film batches has shown that XR-RV3 films have generally good uniformity within one batch (<1.5%), require 24 h to stabilize after the irradiation and their response is roughly independent of dose rate (<5%). However, XR-RV3 films showed large variations (up to 15%) with radiation quality both in standard laboratory and in clinical conditions. As such, and prior to conducting patient skin dose measurements, it is mandatory to choose the appropriate calibration beam quality depending on the characteristics of the x ray systems that will be used clinically. In addition, yellow side film irradiations should be preferentially used since they showed a lower dependence on beam parameters compared to white side film irradiations. Finally, among the six different fit equations tested in this work, typically used third order polynomials and more rational and simplistic equations, of the form dose inversely proportional to pixel value, were both found to provide satisfactory results. Fitting-related uncertainty was clearly identified as a major contributor to the overall film dosimetry uncertainty with up to 40% error on the dose estimate. CONCLUSIONS: The overall uncertainty associated with the use of XR RV3 films to determine skin dose in the interventional environment can realistically be estimated to be around 20% (k = 1). This uncertainty can be reduced to within 5% if carefully monitoring scanner, film, and fitting-related errors or it can easily increase to over 40% if minimal care is not taken. This work demonstrates the importance of appropriate calibration, reading, fitting, and other film-related and scan-related processes, which will help improve the accuracy of skin dose measurements in interventional procedures. PMID- 26133621 TI - Pulmonary imaging using respiratory motion compensated simultaneous PET/MR. AB - PURPOSE: Pulmonary positron emission tomography (PET) imaging is confounded by blurring artifacts caused by respiratory motion. These artifacts degrade both image quality and quantitative accuracy. In this paper, the authors present a complete data acquisition and processing framework for respiratory motion compensated image reconstruction (MCIR) using simultaneous whole body PET/magnetic resonance (MR) and validate it through simulation and clinical patient studies. METHODS: The authors have developed an MCIR framework based on maximum a posteriori or MAP estimation. For fast acquisition of high quality 4D MR images, the authors developed a novel Golden-angle RAdial Navigated Gradient Echo (GRANGE) pulse sequence and used it in conjunction with sparsity-enforcing k t FOCUSS reconstruction. The authors use a 1D slice-projection navigator signal encapsulated within this pulse sequence along with a histogram-based gate assignment technique to retrospectively sort the MR and PET data into individual gates. The authors compute deformation fields for each gate via nonrigid registration. The deformation fields are incorporated into the PET data model as well as utilized for generating dynamic attenuation maps. The framework was validated using simulation studies on the 4D XCAT phantom and three clinical patient studies that were performed on the Biograph mMR, a simultaneous whole body PET/MR scanner. RESULTS: The authors compared MCIR (MC) results with ungated (UG) and one-gate (OG) reconstruction results. The XCAT study revealed contrast to-noise ratio (CNR) improvements for MC relative to UG in the range of 21%-107% for 14 mm diameter lung lesions and 39%-120% for 10 mm diameter lung lesions. A strategy for regularization parameter selection was proposed, validated using XCAT simulations, and applied to the clinical studies. The authors' results show that the MC image yields 19%-190% increase in the CNR of high-intensity features of interest affected by respiratory motion relative to UG and a 6%-51% increase relative to OG. CONCLUSIONS: Standalone MR is not the traditional choice for lung scans due to the low proton density, high magnetic susceptibility, and low T2 (*) relaxation time in the lungs. By developing and validating this PET/MR pulmonary imaging framework, the authors show that simultaneous PET/MR, unique in its capability of combining structural information from MR with functional information from PET, shows promise in pulmonary imaging. PMID- 26133622 TI - Assessment of performance and reproducibility of applying a content-based image retrieval scheme for classification of breast lesions. AB - PURPOSE: To develop a new computer-aided diagnosis (CAD) scheme using a content based image retrieval (CBIR) approach for classification between the malignant and benign breast lesions depicted on the digital mammograms and assess CAD performance and reproducibility. METHODS: An image dataset including 820 regions of interest (ROIs) was used. Among them, 431 ROIs depict malignant lesions and 389 depict benign lesions. After applying an image preprocessing process to define the lesion center, two image features were computed from each ROI. The first feature is an average pixel value of a mapped region generated using a watershed algorithm. The second feature is an average pixel value difference between a ROI's center region and the rest of the image. A two-step CBIR approach uses these two features sequentially to search for ten most similar reference ROIs for each queried ROI. A similarity based classification score was then computed to predict the likelihood of the queried ROI depicting a malignant lesion. To assess the reproducibility of the CAD scheme, we selected another independent testing dataset of 100 ROIs. For each ROI in the testing dataset, we added four randomly queried lesion center pixels and examined the variation of the classification scores. RESULTS: The area under the ROC curve (AUC) = 0.962 +/ 0.006 was obtained when applying a leave-one-out validation method to 820 ROIs. Using the independent testing dataset, the initial AUC value was 0.832 +/- 0.040, and using the median classification score of each ROI with five queried seeds, AUC value increased to 0.878 +/- 0.035. CONCLUSIONS: The authors demonstrated that (1) a simple and efficient CBIR scheme using two lesion density distribution related features achieved high performance in classifying breast lesions without actual lesion segmentation and (2) similar to the conventional CAD schemes using global optimization approaches, improving reproducibility is also one of the challenges in developing CAD schemes using a CBIR based regional optimization approach. PMID- 26133623 TI - Comparison of breast specific gamma imaging and molecular breast tomosynthesis in breast cancer detection: Evaluation in phantoms. AB - PURPOSE: Breast specific gamma imaging or molecular breast imaging (BSGI) obtains 2D images of (99m)Tc sestamibi distribution in the breast. Molecular breast tomosynthesis (MBT) maps the tracer distribution in 3D by acquiring multiple projections over a limited angular range. Here, the authors compare the performance of the two technologies in terms of spatial resolution, lesion contrast, and contrast-to-noise ratio (CNR) in phantom studies under conditions of clinically relevant sestamibi dose and imaging time. METHODS: The systems tested were a Dilon 6800 and a MBT prototype developed at the University of Virginia. Both systems comprise a pixelated sodium iodide scintillator, an array of position sensitive photomultipliers, and a parallel hole collimator. The active areas and energy resolution of the systems are similar. System sensitivity, spatial resolution, lesion contrast, and CNR were measured using a Petri dish, a point source phantom, and a breast phantom containing simulated lesions at two depths, respectively. A single BSGI projection was acquired. Five MBT projections were acquired over +/-20 degrees . For both modalities, the total scan count density was comparable to that observed for each in typical 10 min human scans following injection of 22 mCi (814 MBq) of (99m)Tc-sestamibi. To assess the impact of reducing the tracer dose, the pixel counts of projection images were later binomially subsampled by a factor of 2 to give images corresponding to an injected activity of approximately 11 mCi (407 MBq). Both unprocessed (pixelated) BSGI projections and interpolated (smoothed) BSGI images displayed by default on the Dilon 6800 workstation were analyzed. Volumetric images were reconstructed from the MBT projections using a maximum likelihood expectation maximization algorithm and extracted slices were analyzed. RESULTS: Over a depth range of 1.5-7.5 cm, BSGI spatial resolution was 5.6-11.5 mm in unprocessed projections and 5.7-12.0 mm in interpolated images. Over the same range, the in-slice MBT spatial resolution was 6.7-9.4 mm. Lesion contrast was significantly improved with MBT relative to BSGI for five out of eight lesions imaged at either the 22 mCi or the 11 mCi dose level (p < 0.05). At both dose levels, significant improvements in CNR with MBT were also found for five out of eight lesions (9.8, 7.8, 6.2 mm lesions at water depth of 1.7 cm and 9.8, 7.8 mm lesions at water depth of 4.5 cm, p < 0.05). The 6.2 and 4.9 mm lesions located at 4.5 cm below the water surface were not visible in either modality at either activity level. CONCLUSIONS: Under conditions of equal dose, imaging time and similar detectors, compared to BSGI, MBT provided higher lesion contrast, higher CNR, and spatial resolution that was less depth dependent. PMID- 26133624 TI - GMctdospp: Description and validation of a CT dose calculation system. AB - PURPOSE: To develop a Monte Carlo (MC)-based computed tomography (CT) dose estimation method with a graphical user interface with options to define almost arbitrary simulation scenarios, to make calculations sufficiently fast for comfortable handling, and to make the software free of charge for general availability to the scientific community. METHODS: A framework called GMctdospp was developed to calculate phantom and patient doses with the MC method based on the EGSnrc system. A CT scanner was modeled for testing and was adapted to half value layer, beam-shaping filter, z-profile, and tube-current modulation (TCM). To validate the implemented variance reduction techniques, depth-dose and cross profile calculations of a static beam were compared against DOSXYZnrc/EGSnrc. Measurements for beam energies of 80 and 120 kVp at several positions of a CT dose-index (CTDI) standard phantom were compared against calculations of the created CT model. Finally, the efficiency of the adapted code was benchmarked against EGSnrc defaults. RESULTS: The CT scanner could be modeled accurately. The developed TCM scheme was confirmed by the dose measurement. A comparison of calculations to DOSXYZnrc showed no systematic differences. Measurements in a CTDI phantom could be reproduced within 2% average, with a maximal difference of about 6%. Efficiency improvements of about six orders of magnitude were observed for larger organ structures of a chest-examination protocol in a voxelized phantom. In these cases, simulations took 25 s to achieve a statistical uncertainty of ~0.5%. CONCLUSIONS: A fast dose-calculation system for phantoms and patients in a CT examination was developed, successfully validated, and benchmarked. Influences of scan protocols, protection method, and other issues can be easily examined with the developed framework. PMID- 26133625 TI - Detection of urinary bladder mass in CT urography with SPAN. AB - PURPOSE: The authors are developing a computer-aided detection system for bladder cancer on CT urography (CTU). In this study, the authors focused on developing a system for detecting masses fully or partially within the contrast-enhanced (C) region of the bladder. METHODS: With IRB approval, a data set of 70 patients with biopsy-proven bladder lesions fully or partially immersed within the contrast enhanced region (C region) of the bladder was collected for this study: 35 patients for the training set (39 malignant, 7 benign lesions) and 35 patients for the test set (49 malignant, 4 benign lesions). The bladder in the CTU images was automatically segmented using the authors' conjoint level set analysis and segmentation system, which they developed specifically to segment the bladder. A closed contour of the C region of the bladder was generated by maximum intensity projection using the property that the dependently layering contrast material in the bladder will be filled consistently to the same level along all CTU slices due to gravity. Potential lesion candidates within the C region contour were found using the authors' Straightened Periphery ANalysis (SPAN) method. SPAN transforms a bladder wall to a straightened thickness profile, marks suspicious pixels on the profile, and clusters them into regions of interest to identify potential lesion candidates. The candidate regions were automatically segmented using the authors' autoinitialized cascaded level set segmentation method. Twenty three morphological features were automatically extracted from the segmented lesions. The training set was used to determine the best subset of these features using simplex optimization with the leave-one-out case method. A linear discriminant classifier was designed for the classification of bladder lesions and false positives. The detection performance was evaluated on the independent test set by free-response receiver operating characteristic analysis. RESULTS: At the prescreening step, the authors' system achieved 84.4% sensitivity with an average of 4.3 false positives per case (FPs/case) for the training set, and 84.9% sensitivity with 5.4 FPs/case for the test set. After linear discriminant analysis (LDA) classification with the selected features, the FP rate improved to 2.5 FPs/case for the training set, and 4.3 FPs/case for the test set without missing additional true lesions. By varying the threshold for the LDA scores, at 2.5 FPs/case, the sensitivities were 84.4% and 81.1% for the training and test sets, respectively. At 1.7 FPs/case, the sensitivities decreased to 77.8% and 75.5%, respectively. CONCLUSIONS: The results demonstrate the feasibility of the authors' method for detection of bladder lesions fully or partially immersed in the contrast-enhanced region of CTU. PMID- 26133626 TI - A radiation quality correction factor k for well-type ionization chambers for the measurement of the reference air kerma rate of (60)Co HDR brachytherapy sources. AB - PURPOSE: The aim of this study was to investigate whether a chamber-type-specific radiation quality correction factor kQ can be determined in order to measure the reference air kerma rate of (60)Co high-dose-rate (HDR) brachytherapy sources with acceptable uncertainty by means of a well-type ionization chamber calibrated for (192)Ir HDR sources. METHODS: The calibration coefficients of 35 well-type ionization chambers of two different chamber types for radiation fields of (60)Co and (192)Ir HDR brachytherapy sources were determined experimentally. A radiation quality correction factor kQ was determined as the ratio of the calibration coefficients for (60)Co and (192)Ir. The dependence on chamber-to-chamber variations, source-to-source variations, and source strength was investigated. RESULTS: For the PTW Tx33004 (Nucletron source dosimetry system (SDS)) well-type chamber, the type-specific radiation quality correction factor kQ is 1.19. Note that this value is valid for chambers with the serial number, SN >= 315 (Nucletron SDS SN >= 548) onward only. For the Standard Imaging HDR 1000 Plus well-type chambers, the type-specific correction factor kQ is 1.05. Both kQ values are independent of the source strengths in the complete clinically relevant range. The relative expanded uncertainty (k = 2) of kQ is UkQ = 2.1% for both chamber types. CONCLUSIONS: The calibration coefficient of a well-type chamber for radiation fields of (60)Co HDR brachytherapy sources can be calculated from a given calibration coefficient for (192)Ir radiation by using a chamber-type-specific radiation quality correction factor kQ. However, the uncertainty of a (60)Co calibration coefficient calculated via kQ is at least twice as large as that for a direct calibration with a (60)Co source. PMID- 26133627 TI - (90)Y -PET imaging: Exploring limitations and accuracy under conditions of low counts and high random fraction. AB - PURPOSE: (90)Y -positron emission tomography (PET) imaging is becoming a recognized modality for postinfusion quantitative assessment following radioembolization therapy. However, the extremely low counts and high random fraction associated with (90)Y -PET may significantly impair both qualitative and quantitative results. The aim of this work was to study image quality and noise level in relation to the quantification and bias performance of two types of Siemens PET scanners when imaging (90)Y and to compare experimental results with clinical data from two types of commercially available (90)Y microspheres. METHODS: Data were acquired on both Siemens Biograph TruePoint [non-time-of flight (TOF)] and Biograph microcomputed tomography (mCT) (TOF) PET/CT scanners. The study was conducted in three phases. The first aimed to assess quantification and bias for different reconstruction methods according to random fraction and number of true counts in the scan. The NEMA 1994 PET phantom was filled with water with one cylindrical insert left empty (air) and the other filled with a solution of (90)Y . The phantom was scanned for 60 min in the PET/CT scanner every one or two days. The second phase used the NEMA 2001 PET phantom to derive noise and image quality metrics. The spheres and the background were filled with a (90)Y solution in an 8:1 contrast ratio and four 30 min acquisitions were performed over a one week period. Finally, 32 patient data (8 treated with Therasphere((r)) and 24 with SIR-Spheres((r))) were retrospectively reconstructed and activity in the whole field of view and the liver was compared to theoretical injected activity. RESULTS: The contribution of both bremsstrahlung and LSO trues was found to be negligible, allowing data to be decay corrected to obtain correct quantification. In general, the recovered activity for all reconstruction methods was stable over the range studied, with a small bias appearing at extremely high random fraction and low counts for iterative algorithms. Point spread function (PSF) correction and TOF reconstruction in general reduce background variability and noise and increase recovered concentration. Results for patient data indicated a good correlation between the expected and PET reconstructed activities. A linear relationship between the expected and the measured activities in the organ of interest was observed for all reconstruction method used: a linearity coefficient of 0.89 +/- 0.05 for the Biograph mCT and 0.81 +/- 0.05 for the Biograph TruePoint. CONCLUSIONS: Due to the low counts and high random fraction, accurate image quantification of (90)Y during selective internal radionuclide therapy is affected by random coincidence estimation, scatter correction, and any positivity constraint of the algorithm. Nevertheless, phantom and patient studies showed that the impact of number of true and random coincidences on quantitative results was found to be limited as long as ordinary Poisson ordered subsets expectation maximization reconstruction algorithms with random smoothing are used. Adding PSF correction and TOF information to the reconstruction greatly improves the image quality in terms of bias, variability, noise reduction, and detectability. On the patient studies, the total activity in the field of view is in general accurately measured by Biograph mCT and slightly overestimated by the Biograph TruePoint. PMID- 26133628 TI - On the effect of intrafraction motion in a single fraction step-shoot IMRT. AB - PURPOSE: The authors studied the respiratory motion effect in a single step-shoot intensity modulated radiotherapy (IMRT) to assess the basic properties of the uncertainty in the delivered dose due to the unknown starting phase of the motion. METHODS: Using computer simulations, the motion-averaged dose for open beams with various field sizes was calculated for two one-dimensional trajectories with different motion amplitudes at 20 equally spaced starting phases. The properties of the standard deviation (SD) of delivered dose were analyzed. The dependence of SD on the field size, motion amplitude, and delivery time was investigated and experimentally validated. To study effect of number of small monitor unit (MU) segments on the dose uncertainty, the authors generated 1000 pairs of multisegment beams such that each pair consists of two beams with the same total MU and different segment MU. The SD at the central axis point was compared for each pair. RESULTS: The authors proved that the direct time dependent dose accumulation can be calculated using a convolution formula for a single fraction step-shoot IMRT treatment. Single segment simulation showed that the maximum dose uncertainty occurred symmetrically at the beam penumbra for a sinusoidal motion. For other sinusoidal motions (sin(2n) n > 1), the maximum dose uncertainty occurred at asymmetrical locations and may be beyond the penumbra region. The SD of relative dose periodically varied with delivery time with decreasing envelope for both motion trajectories. The SD of absolute dose was a periodic function of the delivery time for a given field size and motion amplitude and was proved to be true for any periodic motion. The SD reduced to zero when the delivery time was an integer multiple of the motion period. Analytical function sigmaA=3betasin(2)pi/Tdeltat 4/3sin(4)pi/Tdeltat+2/3sin(6)pi/Tdeltat was found to fit the delivery time dependence of the SD for motions studied in this paper and was verified with experimental data and an irregular motion. The dose uncertainty increased with motion amplitude and decreased slowly with field size. Simulations for 1000 beam pairs with multiple segments demonstrated that the probability that more small MU segments did not introduce larger dose uncertainty at central axis point for three cutoff small MUs (2.5/5/10) was 55.8%/51.9%/43.4% and 54.6%/54.4%/45%, respectively, for a sin and a sin(4) motion in a conventional treatment. These probabilities became 53.6%/50.9%/47.2% and 51.0%/50.2%/47.8%, respectively, for a hypofractionated treatment. CONCLUSIONS: The periodic dependence of the dose uncertainty on the delivery time can be modeled with an analytic function, and the functional form is independent of motion trajectories in this paper. The relation of dose uncertainty between different dose schemes can be obtained using this function. The dose uncertainty at central axis point for a beam with more small MU segments may not be greater than a beam with less small MU segments. By varying the dose rate of each segment such that the delivery time is close to the integer multiples of the motion period, the interplay effect can be reduced. PMID- 26133629 TI - Single-frequency excitation wideband MRI (SE-WMRI). AB - PURPOSE: In this study, single-frequency excitation wideband magnetic resonance imaging (MRI) (SE-WMRI) was proposed to obtain high-quality accelerated images by reducing phase-encoding steps while applying separation gradients. METHODS: A zig zag k-space trajectory with reduced phase-encoding steps and an increased readout sampling rate was proposed. A unique gradient design with buffer intervals near the trajectory turns was employed to avoid undersampling and image artifacts. A gridding method and Fourier transform were used for image reconstruction. Quantitative analysis was performed on phantom images to investigate the characteristics of the acceleration method. RESULTS: The proposed method showed evident improvements in the accelerated phantom images, substantially reducing the ringing and blurring artifacts found using previous methods. Furthermore, the accelerated images exhibited the same signal-to-noise ratio as standard imaging. The accelerated in vivo experiment also produced the same quality as standard imaging. CONCLUSIONS: The proposed SE-WMRI method can effectively remove image artifacts and acquire images of higher temporal or spatial resolutions with less compromise. PMID- 26133630 TI - A data-mining framework for large scale analysis of dose-outcome relationships in a database of irradiated head and neck cancer patients. AB - PURPOSE: To develop a hypothesis-generating framework for automatic extraction of dose-outcome relationships from an in-house, analytic oncology database. METHODS: Dose-volume histograms (DVH) and clinical outcomes have been routinely stored to the authors' database for 684 head and neck cancer patients treated from 2007 to 2014. Database queries were developed to extract outcomes that had been assessed for at least 100 patients, as well as DVH curves for organs-at-risk (OAR) that were contoured for at least 100 patients. DVH curves for paired OAR (e.g., left and right parotids) were automatically combined and included as additional structures for analysis. For each OAR-outcome combination, only patients with both OAR and outcome records were analyzed. DVH dose points, DVt, at a given normalized volume threshold Vt were stratified into two groups based on severity of toxicity outcomes after treatment completion. The probability of an outcome was modeled at each Vt = [0%, 1%, ..., 100%] by logistic regression. Notable OAR outcome combinations were defined as having statistically significant regression parameters (p < 0.05) and an odds ratio of at least 1.05 (5% increase in odds per Gy). RESULTS: A total of 57 individual and combined structures and 97 outcomes were queried from the database. Of all possible OAR-outcome combinations, 17% resulted in significant logistic regression fits (p < 0.05) having an odds ratio of at least 1.05. Further manual inspection revealed a number of reasonable models based on either reported literature or proximity between neighboring OARs. The data-mining algorithm confirmed the following well-known OAR-dose/outcome relationships: dysphagia/larynx, voice changes/larynx, esophagitis/esophagus, xerostomia/parotid glands, and mucositis/oral mucosa. Several surrogate relationships, defined as OAR not directly attributed to an outcome, were also observed, including esophagitis/larynx, mucositis/mandible, and xerostomia/mandible. CONCLUSIONS: Prospective collection of clinical data has enabled large-scale analysis of dose-outcome relationships. The current data mining framework revealed both known and novel dosimetric and clinical relationships, underscoring the potential utility of this analytic approach in hypothesis generation. Multivariate models and advanced, 3D dosimetric features may be necessary to further evaluate the complex relationship between neighboring OAR and observed outcomes. PMID- 26133631 TI - Internal respiratory surrogate in multislice 4D CT using a combination of Fourier transform and anatomical features. AB - PURPOSE: The purpose of this study was to develop a novel algorithm to create a robust internal respiratory signal (IRS) for retrospective sorting of four dimensional (4D) computed tomography (CT) images. METHODS: The proposed algorithm combines information from the Fourier transform of the CT images and from internal anatomical features to form the IRS. The algorithm first extracts potential respiratory signals from low-frequency components in the Fourier space and selected anatomical features in the image space. A clustering algorithm then constructs groups of potential respiratory signals with similar temporal oscillation patterns. The clustered group with the largest number of similar signals is chosen to form the final IRS. To evaluate the performance of the proposed algorithm, the IRS was computed and compared with the external respiratory signal from the real-time position management (RPM) system on 80 patients. RESULTS: In 72 (90%) of the 4D CT data sets tested, the IRS computed by the authors' proposed algorithm matched with the RPM signal based on their normalized cross correlation. For these data sets with matching respiratory signals, the average difference between the end inspiration times (Deltatins) in the IRS and RPM signal was 0.11 s, and only 2.1% of Deltatins were more than 0.5 s apart. In the eight (10%) 4D CT data sets in which the IRS and the RPM signal did not match, the average Deltatins was 0.73 s in the nonmatching couch positions, and 35.4% of them had a Deltatins greater than 0.5 s. At couch positions in which IRS did not match the RPM signal, a correlation-based metric indicated poorer matching of neighboring couch positions in the RPM-sorted images. This implied that, when IRS did not match the RPM signal, the images sorted using the IRS showed fewer artifacts than the clinical images sorted using the RPM signal. CONCLUSIONS: The authors' proposed algorithm can generate robust IRSs that can be used for retrospective sorting of 4D CT data. The algorithm is completely automatic and requires very little processing time. The algorithm is cost efficient and can be easily adopted for everyday clinical use. PMID- 26133632 TI - Performance of today's dual energy CT and future multi energy CT in virtual non contrast imaging and in iodine quantification: A simulation study. AB - PURPOSE: To study the performance of different dual energy computed tomography (DECT) techniques, which are available today, and future multi energy CT (MECT) employing novel photon counting detectors in an image-based material decomposition task. METHODS: The material decomposition performance of different energy-resolved CT acquisition techniques is assessed and compared in a simulation study of virtual non-contrast imaging and iodine quantification. The material-specific images are obtained via a statistically optimal image-based material decomposition. A projection-based maximum likelihood approach was used for comparison with the authors' image-based method. The different dedicated dual energy CT techniques are simulated employing realistic noise models and x-ray spectra. The authors compare dual source DECT with fast kV switching DECT and the dual layer sandwich detector DECT approach. Subsequent scanning and a subtraction method are studied as well. Further, the authors benchmark future MECT with novel photon counting detectors in a dedicated DECT application against the performance of today's DECT using a realistic model. Additionally, possible dual source concepts employing photon counting detectors are studied. RESULTS: The DECT comparison study shows that dual source DECT has the best performance, followed by the fast kV switching technique and the sandwich detector approach. Comparing DECT with future MECT, the authors found noticeable material image quality improvements for an ideal photon counting detector; however, a realistic detector model with multiple energy bins predicts a performance on the level of dual source DECT at 100 kV/Sn 140 kV. Employing photon counting detectors in dual source concepts can improve the performance again above the level of a single realistic photon counting detector and also above the level of dual source DECT. CONCLUSIONS: Substantial differences in the performance of today's DECT approaches were found for the application of virtual non-contrast and iodine imaging. Future MECT with realistic photon counting detectors currently can only perform comparably to dual source DECT at 100 kV/Sn 140 kV. Dual source concepts with photon counting detectors could be a solution to this problem, promising a better performance. PMID- 26133633 TI - Efficient imaging of midbrain nuclei using inverse double-echo steady-state acquisition. AB - PURPOSE: Imaging of midbrain nuclei using T2- or T2*-weighted MRI often entails long echo time, leading to long scan time. In this study, an inverse double-echo steady-state (iDESS) technique is proposed for efficiently depicting midbrain nuclei. METHODS: Thirteen healthy subjects participated in this study. iDESS was performed along with two sets of T2*-weighted spoiled gradient-echo images (SPGR1, with scan time identical to iDESS and SPGR2, using clinical scanning parameters as a reference standard) for comparison. Generation of iDESS composite images combining two echo signals was optimized for maximal contrast-to-noise ratio (CNR) between the red nuclei and surrounding tissues. Signal-to-noise ratios (SNRs) were calculated from the occipital lobe. Comparison was also made using phase-enhanced images as in standard susceptibility-weighted imaging (SWI). RESULTS: The iDESS images present significantly higher SNR efficiency (171.3) than SPGR1 (158.7, p = 0.013) and SPGR2 (95.5, p < 10(-8)). iDESS CNR efficiency (19.2) is also significantly greater than SPGR1 (6.9, p < 10(-6)) and SPGR2 (14.3, p = 0.0016). Compared with DESS, iDESS provides further advantage on enhanced phase information and hence improved contrast on SWI-processed images. CONCLUSIONS: iDESS efficiently depicts midbrain nuclei with improved CNR efficiency, increased SNR efficiency, and reduced scan time and is less prone to susceptibility signal loss from air-tissue interfaces. PMID- 26133634 TI - Resting myocardial blood flow quantification using contrast-enhanced magnetic resonance imaging in the presence of stenosis: A computational fluid dynamics study. AB - PURPOSE: The extent to which atherosclerotic plaques affect contrast agent (CA) transport in the coronary arteries and, hence, quantification of myocardial blood flow (MBF) using magnetic resonance imaging (MRI) is unclear. The purpose of this work was to evaluate the influence of plaque induced stenosis both on CA transport and on the accuracy of MBF quantification. METHODS: Computational fluid dynamics simulations in a high-detailed realistic vascular model were employed to investigate CA bolus transport in the coronary arteries. The impact of atherosclerosis was analyzed by inserting various medium- to high-grade stenoses in the vascular model. The influence of stenosis morphology was examined by varying the stenosis shapes but keeping the area reduction constant. Errors due to CA bolus transport were analyzed using the tracer-kinetic model MMID4. RESULTS: Dispersion of the CA bolus was found in all models and for all outlets, but with a varying magnitude. The impact of stenosis was complex: while high grade stenoses amplified dispersion, mild stenoses reduced the effect. Morphology was found to have a marked influence on dispersion for a small number of outlets in the post-stenotic region. Despite this marked influence on the concentration time curves, MBF errors were less affected by stenosis. In total, MBF was underestimated by -7.9% to -44.9%. CONCLUSIONS: The presented results reveal that local hemodynamics in the coronary vasculature appears to have a direct impact on CA bolus dispersion. Inclusion of atherosclerotic plaques resulted in a complex alteration of this effect, with both degree of area reduction and stenosis morphology affecting the amount of dispersion. This strong influence of vascular transport effects impairs the accuracy of MRI-based MBF quantification techniques and, potentially, other bolus-based perfusion measurement techniques like computed tomography perfusion imaging. PMID- 26133635 TI - Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections. AB - PURPOSE: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)]. METHODS: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11-0.33 MPa, 306 kHz driving frequency) DefinityTM microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water path control images. RESULTS: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors' previous experimental measurements using source-based skull corrections O'Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285-1294 (2014)]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood-brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections. CONCLUSIONS: Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography. PMID- 26133637 TI - Comment on "ROC analysis in patient specific quality assurance" [Med. Phys. 40(4), 042103 (7pp.) (2013)]. PMID- 26133636 TI - Microcalcification detectability using a bench-top prototype photon-counting breast CT based on a Si strip detector. AB - PURPOSE: To investigate the feasibility of detecting breast microcalcification (MUCa) with a dedicated breast computed tomography (CT) system based on energy resolved photon-counting silicon (Si) strip detectors. METHODS: The proposed photon-counting breast CT system and a bench-top prototype photon-counting breast CT system were simulated using a simulation package written in matlab to determine the smallest detectable MUCa. A 14 cm diameter cylindrical phantom made of breast tissue with 20% glandularity was used to simulate an average-sized breast. Five different size groups of calcium carbonate grains, from 100 to 180 MUm in diameter, were simulated inside of the cylindrical phantom. The images were acquired with a mean glandular dose (MGD) in the range of 0.7-8 mGy. A total of 400 images was used to perform a reader study. Another simulation study was performed using a 1.6 cm diameter cylindrical phantom to validate the experimental results from a bench-top prototype breast CT system. In the experimental study, a bench-top prototype CT system was constructed using a tungsten anode x-ray source and a single line 256-pixels Si strip photon-counting detector with a pixel pitch of 100 MUm. Calcium carbonate grains, with diameter in the range of 105-215 MUm, were embedded in a cylindrical plastic resin phantom to simulate MUCas. The physical phantoms were imaged at 65 kVp with an entrance exposure in the range of 0.6-8 mGy. A total of 500 images was used to perform another reader study. The images were displayed in random order to three blinded observers, who were asked to give a 4-point confidence rating on each image regarding the presence of MUCa. The MUCa detectability for each image was evaluated by using the average area under the receiver operating characteristic curve (AUC) across the readers. RESULTS: The simulation results using a 14 cm diameter breast phantom showed that the proposed photon-counting breast CT system can achieve high detection accuracy with an average AUC greater than 0.89 +/- 0.07 for MUCas larger than 120 MUm in diameter at a MGD of 3 mGy. The experimental results using a 1.6 cm diameter breast phantom showed that the prototype system can achieve an average AUC greater than 0.98 +/- 0.01 for MUCas larger than 140 MUm in diameter using an entrance exposure of 1.2 mGy. CONCLUSIONS: The proposed photon-counting breast CT system based on a Si strip detector can potentially offer superior image quality to detect MUCa with a lower dose level than a standard two-view mammography. PMID- 26133639 TI - Comment on "Characterization of the Exradin W1 scintillator for use in radiotherapy" [Med. Phys. 42, 297-304 (2015)]. PMID- 26133638 TI - Response to "Comment on 'ROC analysis in patient specific quality assurance' " [Med. Phys. 40, 042103 (7pp.) (2013)]. PMID- 26133640 TI - Response to "Comment on 'Characterization of the Exradin W1 scintillator for use in radiotherapy' " [Med. Phys. 42, 297-304 (2015)]. PMID- 26133642 TI - Making eye contact without awareness. AB - Direct gaze is a potent non-verbal signal that establishes a communicative connection between two individuals, setting the course for further interactions. Although consciously perceived faces with direct gaze have been shown to capture attention, it is unknown whether an attentional preference for these socially meaningful stimuli exists even in the absence of awareness. In two experiments, we recorded participants' eye movements while they were exposed to faces with direct and averted gaze rendered invisible by interocular suppression. Participants' inability to correctly guess the occurrence of the faces in a manual forced-choice task demonstrated complete unawareness of the faces. However, eye movements were preferentially directed towards faces with direct compared to averted gaze, indicating a specific sensitivity to others' gaze directions even without awareness. This oculomotor preference suggests that a rapid and automatic establishment of mutual eye contact constitutes a biological advantage, which could be mediated by fast subcortical pathways in the human brain. PMID- 26133641 TI - Reptilian Transcriptomes v2.0: An Extensive Resource for Sauropsida Genomics and Transcriptomics. AB - Despite the availability of deep-sequencing techniques, genomic and transcriptomic data remain unevenly distributed across phylogenetic groups. For example, reptiles are poorly represented in sequence databases, hindering functional evolutionary and developmental studies in these lineages substantially more diverse than mammals. In addition, different studies use different assembly and annotation protocols, inhibiting meaningful comparisons. Here, we present the "Reptilian Transcriptomes Database 2.0," which provides extensive annotation of transcriptomes and genomes from species covering the major reptilian lineages. To this end, we sequenced normalized complementary DNA libraries of multiple adult tissues and various embryonic stages of the leopard gecko and the corn snake and gathered published reptilian sequence data sets from representatives of the four extant orders of reptiles: Squamata (snakes and lizards), the tuatara, crocodiles, and turtles. The LANE runner 2.0 software was implemented to annotate all assemblies within a single integrated pipeline. We show that this approach increases the annotation completeness of the assembled transcriptomes/genomes. We then built large concatenated protein alignments of single-copy genes and inferred phylogenetic trees that support the positions of turtles and the tuatara as sister groups of Archosauria and Squamata, respectively. The Reptilian Transcriptomes Database 2.0 resource will be updated to include selected new data sets as they become available, thus making it a reference for differential expression studies, comparative genomics and transcriptomics, linkage mapping, molecular ecology, and phylogenomic analyses involving reptiles. The database is available at www.reptilian-transcriptomes.org and can be enquired using a wwwblast server installed at the University of Geneva. PMID- 26133643 TI - Drug fever as an adverse effect of acitretin in complicated psoriasis patient. AB - We present a case of a 63-year old man with severe chronic plaque psoriasis and a recent history of lung cancer, wherein fever appeared suddenly after initiation of treatment with low dose acitretin. Tumor recurrence or infection was not found during extensive examinations, nevertheless the patient was empirically treated with broad-spectrum antibiotics without any effect on fever. Immediately after discontinuation of acitretin therapy, the fever disappeared. The patient was followed for next 2 years, during this period similar problems did not reappear, although there has been a relapse of psoriasis and the patient was switched later on biological treatment. PMID- 26133644 TI - Leptin and metabolic syndrome in patients with Duchenne/Becker muscular dystrophy. AB - OBJECTIVES: To determine whether patients with Duchenne/Becker muscular dystrophy (DMD/BMD) have components of metabolic syndrome (MetSy) and to evaluate whether leptin is associated with components of MetSy. METHODS: This study included 78 patients (nine, <6 years of age; 54, 6 to <16 years of age; and 15 patients, >=16 years of age). Obesity and body fat mass were determined by waist circumference and dual-energy X-ray absorptiometry, respectively. A 12-h fasting blood sample was collected in the morning. Patients were categorized into four groups according to the number of criteria for MetSy: group 0: none; group 1: one; group 2: two and group 3: three or more criteria. RESULTS: All age groups showed components of MetSy. The concentration of these components was significantly higher in patients >=16 years old. The prevalence of hypertriglyceridemia was from ~37% to 46% in all age groups. The prevalence of MetSy was 7.1% for patients from 6 to <16 years of age and 24% for patients >=16 years of age. Serum leptin levels increased significantly (P < 0.05) with age; the highest (13.43 +/- 9.4 ng/ml) value was observed in patients >16 years of age. Total leptin was correlated with the number of patients with MetSy (r = 0.383; P = 0.001). CONCLUSIONS: Components of MetSy are significant in patients with DMD/BMD. A high prevalence of hypertriglyceridemia was observed. Younger patients with DMD/BMD have risk factors for MetSy. Although leptin increased according to different degrees of MetSy, this relation disappeared when the body fat was corrected by leptin; therefore, the association could be caused by a common risk factor-fat. PMID- 26133645 TI - Rural Food and Physical Activity Assessment Using an Electronic Tablet-Based Application, New York, 2013-2014. AB - INTRODUCTION: A community's built environment can influence health behaviors. Rural populations experience significant health disparities, yet built environment studies in these settings are limited. We used an electronic tablet based community assessment tool to conduct built environment audits in rural settings. The primary objective of this qualitative study was to evaluate the usefulness of the tool in identifying barriers and facilitators to healthy eating and active living. The second objective was to understand resident perspectives on community features and opportunities for improvement. METHODS: Participants were recruited from 4 rural communities in New York State. Using the tool, participants completed 2 audits, which consisted of taking pictures and recording audio narratives about community features perceived as assets or barriers to healthy eating and active living. Follow-up focus groups explored the audit experience, data captured, and opportunities for change. RESULTS: Twenty-four adults (mean age, 69.4 y (standard deviation, 13.2 y), 6 per community, participated in the study. The most frequently captured features related to active living were related to roads, sidewalks, and walkable destinations. Restaurants, nontraditional food stores, and supermarkets were identified in the food environment in relation to the cost, quality, and selection of healthy foods available. In general, participants found the assessment tool to be simple and enjoyable to use. CONCLUSION: An electronic tablet-based tool can be used to assess rural food and physical activity environments and may be useful in identifying and prioritizing resident-led change initiatives. This resident-led assessment approach may also be helpful for informing and evaluating rural community-based interventions. PMID- 26133646 TI - Self-Management and Health Care Use in an Adolescent and Young Adult Medicaid Population With Differing Chronic Illnesses. AB - INTRODUCTION: Few studies of adults question the validity of the claim that self management reduces the use of health care services and, as a result, health care costs. The aim of our study was to determine the relationship between self management and health care use in a population of adolescent and young adult recipients of North Carolina Medicaid with chronic health conditions, who received care in either the pediatric or adult clinic. Our secondary objective was to characterize the patterns of health care use among this same population. METHODS: One hundred and fifty adolescents or young adults aged 14 to 29 were recruited for this study. Participants completed a demographics questionnaire and the self-management subdomain of the University of North Carolina TRxANSITION Scale. Information on each participant's emergency department and inpatient use was obtained by using the North Carolina Medicaid Provider Portal. RESULTS: This cohort had a high level of emergency health care use; average lifetime use was 3.18 (standard deviation [SD], 5.58) emergency department visits, 2.02 (SD, 3.42) inpatient visits, and 12.5 (SD, 23.9 ) days as an inpatient. Age group (pediatric or adult), diagnosis, race/ethnicity, and sex were controlled for in all analyses. Results indicate that patients with a high rate of disease self management had more emergency department visits and hospitalizations and a longer length of stay in the hospital than did those with a low rate. CONCLUSION: In a group of North Carolina Medicaid recipients with chronic conditions, better self management is associated with more health care use. This is likely the result of many factors, including more interactions with health care professionals, greater ability to recognize the need for emergency medical attention, and the use of the emergency department for primary health care. PMID- 26133647 TI - Meeting the Healthy People 2020 Objectives to Reduce Cancer Mortality. AB - INTRODUCTION: Healthy People 2020 (HP2020) calls for a 10% to 15% reduction in death rates from 2007 to 2020 for selected cancers. Trends in death rates can be used to predict progress toward meeting HP2020 targets. METHODS: We used mortality data from 1975 through 2009 and population estimates and projections to predict deaths for all cancers and the top 23 cancers among men and women by race. We apportioned changes in deaths from population risk and population growth and aging. RESULTS: From 1975 to 2009, the number of cancer deaths increased among white and black Americans primarily because of an aging white population and a growing black population. Overall, age-standardized cancer death rates (risk) declined in all groups. From 2007 to 2020, rates are predicted to continue to decrease while counts of deaths are predicted to increase among men (15%) and stabilize among women (increase <10%). Declining death rates are predicted to meet HP2020 targets for cancers of the female breast, lung and bronchus, cervix and uterus, colon and rectum, oral cavity and pharynx, and prostate, but not for melanoma. CONCLUSION: Cancer deaths among women overall are predicted to increase by less than 10%, because of, in part, declines in breast, cervical, and colorectal cancer deaths among white women. Increased efforts to promote cancer prevention and improve survival are needed to counter the impact of a growing and aging population on the cancer burden and to meet melanoma target death rates. PMID- 26133648 TI - Impact of Health Insurance Expansions on Nonelderly Adults With Hypertension. AB - INTRODUCTION: Hypertension is a risk factor for cardiovascular disease (CVD), the leading cause of death in the United States. The treatment and control of hypertension is inadequate, especially among patients without health insurance coverage. The Affordable Care Act offered an opportunity to improve hypertension management by increasing the number of people covered by insurance. This study predicts the long-term effects of improved hypertension treatment rates due to insurance expansions on the prevalence and mortality rates of CVD of nonelderly Americans with hypertension. METHODS: We developed a state-transition model to simulate the lifetime health events of the population aged 25 to 64 years. We modeled the effects of insurance coverage expansions on the basis of published findings on the relationship between insurance coverage, use of antihypertensive medications, and CVD-related events and deaths. RESULTS: The model projected that currently anticipated health insurance expansions would lead to a 5.1% increase in treatment rate among hypertensive patients. Such an increase in treatment rate is estimated to lead to 111,000 fewer new coronary heart disease events, 63,000 fewer stroke events, and 95,000 fewer CVD-related deaths by 2050. The estimated benefits were slightly greater for men than for women and were greater among nonwhite populations. CONCLUSION: Federal and state efforts to expand insurance coverage among nonelderly adults could yield significant health benefits in terms of CVD prevalence and mortality rates and narrow the racial/ethnic disparities in health outcomes for patients with hypertension. PMID- 26133649 TI - Delineation of 134Cs uptake pathways (seawater and food) in the variegated scallop Mimachlamys varia. AB - Among bivalves, scallops have been shown to be good bioindicator species for radionuclide monitoring. The present paper looked at the Cs bioaccumulation capacities of the variegated scallop Mimachlamys varia exposed separately via seawater and food under laboratory conditions. Results were compared with data previously obtained for the king scallop Pecten maximus, the only Pectinid species for which Cs accumulation has been studied in laboratory. Results indicated that M. varia has higher uptake capacity (CF: 1.86 +/- 0.08) but lower absorption efficiency (A0l: 33 +/- 5%) than P. maximus when exposed to waterborne Cs (CF of P. maximus: 0.94 +/- 0.05 and A0l: 45 +/- 3%). When scallops were fed radiolabeled phytoplankton, the assimilation efficiency of Cs was similar for the two species (AE: 24 +/- 3% for M. varia and 28 +/- 4% for P. maximus). Interspecific differences in terms of accumulation and retention, can be explained by physiological factors (including size of individuals) and/or difference in storage mechanisms. Indeed, organotropism differed between the two scallop species, suggesting the occurrence of specific redistribution mechanisms towards the tissues involved in Cs storage, excretion and detoxification. Finally, the present study examined the relative contribution of the different exposure pathways (seawater and food) to global (134)Cs bioaccumulation for M. varia. Results showed that food constitutes the main accumulation pathway, contributing for 77% of the global (134)Cs bioaccumulation. PMID- 26133650 TI - A low pre-infall mass for the Carina dwarf galaxy from disequilibrium modelling. AB - Dark matter-only simulations of galaxy formation predict many more subhalos around a Milky Way-like galaxy than the number of observed satellites. Proposed solutions require the satellites to inhabit dark matter halos with masses 10(9) 10(10 )Msun at the time they fell into the Milky Way. Here we use a modelling approach, independent of cosmological simulations, to obtain a pre-infall mass of 3.6(-2.3)(+3.8) * 10(8) Msun for one of the Milky Way's satellites: Carina. This determination of a low halo mass for Carina can be accommodated within the standard model only if galaxy formation becomes stochastic in halos below ~10(10 )Msun. Otherwise Carina, the eighth most luminous Milky Way dwarf, would be expected to inhabit a significantly more massive halo. The implication of this is that a population of 'dark dwarfs' should orbit the Milky Way: halos devoid of stars and yet more massive than many of their visible counterparts. PMID- 26133651 TI - Primary lung tumor segmentation from PET-CT volumes with spatial-topological constraint. AB - PURPOSE: Accurate lung tumor segmentation is a prerequisite for effective radiation therapy and surgical planning. However, tumor delineation is challenging when the tumor boundaries are indistinct on PET or CT. To address this problem, we developed a segmentation method to improve the delineation of primary lung tumors from PET-CT images. METHODS: We formulated the segmentation problem as a label information propagation process in an iterative manner. Our model incorporates spatial-topological information from PET and local intensity changes from CT. The topological information of the regions was extracted based on the metabolic activity of different tissues. The spatial-topological information moderates the amount of label information that a pixel receives: The label information attenuates as the spatial distance increases and when crossing different topological regions. Thus, the spatial-topological constraint assists accurate tumor delineation and separation. The label information propagation and transition model are solved under a random walk framework. RESULTS: Our method achieved an average DSC of 0.848 +/- 0.036 and HD (mm) of 8.652 +/- 4.532 on 40 patients with lung cancer. The t test showed a significant improvement (p value < 0.05) in segmentation accuracy when compared to eight other methods. Our method was better able to delineate tumors that had heterogeneous FDG uptake and which abutted adjacent structures that had similar densities. CONCLUSIONS: Our method, using a spatial-topological constraint, provided better lung tumor delineation, in particular, when the tumor involved or abutted the chest wall and the mediastinum. PMID- 26133652 TI - A study of crowdsourced segment-level surgical skill assessment using pairwise rankings. AB - PURPOSE: Currently available methods for surgical skills assessment are either subjective or only provide global evaluations for the overall task. Such global evaluations do not inform trainees about where in the task they need to perform better. In this study, we investigated the reliability and validity of a framework to generate objective skill assessments for segments within a task, and compared assessments from our framework using crowdsourced segment ratings from surgically untrained individuals and expert surgeons against manually assigned global rating scores. METHODS: Our framework includes (1) a binary classifier trained to generate preferences for pairs of task segments (i.e., given a pair of segments, specification of which one was performed better), (2) computing segment level percentile scores based on the preferences, and (3) predicting task-level scores using the segment-level scores. We conducted a crowdsourcing user study to obtain manual preferences for segments within a suturing and knot-tying task from a crowd of surgically untrained individuals and a group of experts. We analyzed the inter-rater reliability of preferences obtained from the crowd and experts, and investigated the validity of task-level scores obtained using our framework. In addition, we compared accuracy of the crowd and expert preference classifiers, as well as the segment- and task-level scores obtained from the classifiers. RESULTS: We observed moderate inter-rater reliability within the crowd (Fleiss' kappa, kappa = 0.41) and experts (kappa = 0.55). For both the crowd and experts, the accuracy of an automated classifier trained using all the task segments was above par as compared to the inter-rater agreement [crowd classifier 85 % (SE 2 %), expert classifier 89 % (SE 3 %)]. We predicted the overall global rating scores (GRS) for the task with a root-mean-squared error that was lower than one standard deviation of the ground-truth GRS. We observed a high correlation between segment-level scores (rho >= 0.86) obtained using the crowd and expert preference classifiers. The task-level scores obtained using the crowd and expert preference classifier were also highly correlated with each other (rho >= 0.84), and statistically equivalent within a margin of two points (for a score ranging from 6 to 30). Our analyses, however, did not demonstrate statistical significance in equivalence of accuracy between the crowd and expert classifiers within a 10 % margin. CONCLUSIONS: Our framework implemented using crowdsourced pairwise comparisons leads to valid objective surgical skill assessment for segments within a task, and for the task overall. Crowdsourcing yields reliable pairwise comparisons of skill for segments within a task with high efficiency. Our framework may be deployed within surgical training programs for objective, automated, and standardized evaluation of technical skills. PMID- 26133653 TI - Rate of Reoperation Is Not the Same as Rate of Migration. PMID- 26133654 TI - In-Situ ESEM and EELS Observation of Water Uptake and Ice Formation in Multilayer Graphene Oxide. AB - Graphene oxide (GO) is hydrophilic and swells significantly when in contact with water. Here, we investigate the change in thickness of multilayer graphene oxide membranes due to intercalation of water, via humidity-controlled observation in an environmental scanning electron microscope (ESEM). The thickness increases reproducibly with increasing relative humidity. Electron energy loss spectroscopy (EELS) reveals the existence of water ice under cryogenic conditions, even in high vacuum environment. Additionally, we demonstrate that freezing then thawing water trapped in the multilayer graphene oxide membrane leads to the opening up of micron-scale inter-lamellar voids due to the expansion of ice crystals. PMID- 26133655 TI - Uric acid as a modulator of glucose and lipid metabolism. AB - In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine. Uric acid is similarly produced in the liver, adipose tissue and muscle and is primarily excreted through the urinary tract. Several factors, including a high-fructose diet and the use of xenobiotics and alcohol, contribute to hyperuricaemia. Hyperuricaemia belongs to a cluster of metabolic and haemodynamic abnormalities, called metabolic syndrome, characterised by abdominal obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. Hyperuricaemia reduction in the Pound mouse or fructose-fed rats, as well as hyperuricaemia induction by uricase inhibition in rodents and studies using cell culture have suggested that uric acid plays an important role in the development of metabolic syndrome. These studies have shown that high uric acid levels regulate the oxidative stress, inflammation and enzymes associated with glucose and lipid metabolism, suggesting a mechanism for the impairment of metabolic homeostasis. Humans lacking uricase, the enzyme responsible for uric acid degradation, are susceptible to these effects. In this review, we summarise the current knowledge of the effects of uric acid on the regulation of metabolism, primarily focusing on liver, adipose tissue and skeletal muscle. PMID- 26133656 TI - rAdinbitor, a disintegrin from Agkistrodon halys brevicaudus stejneger, inhibits tumorigenicity of hepatocarcinoma via enhanced anti-angiogenesis and immunocompetence. AB - Adinbitor is a disintegrin previously obtained from Agkistrodon halys brevicaudus stejneger by our group. Here, we investigated the in vitro and in vivo anti-tumor activities of recombinant Adinbitor (rAdinbitor). rAdinbitor stimulation can inhibit the in vitro proliferation, migration and invasion capacities of murine hepatocarcinoma H22 and Hca-F cells. The administrations of rAdinbitor either by gavage or intraperitoneal injection suppress the tumor malignancy and prolong the survival rate and time of H22-transplanted mice. The number and size of formed blood vessels decreased dramatically in tumorous tissues in that the expression levels of vascular endothelial growth factor (VEGF) and cluster of differentiation 34 (CD34) were significantly decreased in responding to rAdinbitor treatment. The protein levels of IL-18 and IgG increased significantly in the serum of H22-transplanted tumor mice with rAdinbitor treatment. rAdinbitor shows in vitro and in vivo anti-tumor effects as an angiogenesis inhibitor and immunocompetence enhancer. PMID- 26133657 TI - Effect of selective estrogen receptor modulators on metabolic homeostasis. AB - Selective estrogen receptor modulators (SERMs) are estrogen receptor (ER) ligands that exhibit either estrogen agonistic or antagonistic activity in a tissue specific manner. The first and second generation SERMs, tamoxifen and raloxifene, are used for treatment of ER positive breast cancer and postmenopausal osteoporosis respectively. The third-generation SERM, bazedoxifene (BZA), effectively prevents osteoporosis while blocking the estrogenic stimulation in breast and uterus. Notably, BZA combined with conjugated estrogens (CE) in a tissue-selective estrogen complex (TSEC) is a new menopausal treatment. Postmenopausal estrogen deficiency predisposes to metabolic syndrome and type 2 diabetes, and therefore the effects of SERMs and TSECs on metabolic homeostasis are gaining attention. In this article, we summarize current knowledge about the impact of SERMs on metabolic homeostasis and metabolic disorders in animal models and postmenopausal women. PMID- 26133658 TI - alpha-Lipoic acid attenuates LPS-induced liver injury by improving mitochondrial function in association with GR mitochondrial DNA occupancy. AB - alpha-Lipoic acid (LA) has been demonstrated to be a key regulator of energy metabolism. However, whether LA can protect the liver from inflammation, as well as the underlying mechanism involved, are still largely unclear. In the present study, mice treated with lipopolysaccharide (LPS) and injected with LA were used as a model. Liver injury, energy metabolism and mitochondrial regulation were investigated to assess the protective effect of LA on the liver and explore the possible mechanisms involved. Our results showed that LA attenuated liver injury, as evidenced by the decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels after LA treatment compared with the LPS-treated group. The hepatic ATP and NADH levels, expression levels of most mitochondrial DNA (mtDNA)-encoded genes as well as mitochondrial complex I, IV and V activities were all significantly increased in the LA-treated group compared with the LPS treated group. Levels of Sirt3 protein, which is essential for the regulation of mitochondrial metabolism, were also increased in the LA-treated group. Regarding the regulation of mtDNA-encoded genes expression, we observed no obvious change in the methylation status of the mtDNA D-loop region. However, compared to the LPS-treated group, LA treatment increased glucocorticoid receptor (GR) protein expression in the liver, as well as the level of GR occupancy on the mtDNA D-loop region. Our study demonstrates that LA exerts a liver-protective effect in an inflammation state by improving mitochondrial function. Furthermore, to the best of our knowledge, we demonstrate for the first time that GR may be involved in this effect via an enhanced binding to the mtDNA transcriptional control region, thereby regulating the expression of mtDNA-encoded genes. PMID- 26133659 TI - Metabolic endotoxemia with obesity: Is it real and is it relevant? AB - Obesity is associated with metabolic derangements in multiple tissues, which contribute to the progression of insulin resistance and the metabolic syndrome. The underlying stimulus for these metabolic derangements in obesity are not fully elucidated, however recent evidence in rodents and humans suggests that systemic, low level elevations of gut derived endotoxin (lipopolysaccharide, LPS) may play an important role in obesity related, whole-body and tissue specific metabolic perturbations. LPS initiates a well-characterized signaling cascade that elicits many pro- and anti-inflammatory pathways when bound to its receptor, Toll-Like Receptor 4 (TLR4). Low-grade elevation in plasma LPS has been termed "metabolic endotoxemia" and this state is associated with a heightened pro-inflammatory and oxidant environment often observed in obesity. Given the role of inflammatory and oxidative stress in the etiology of obesity related cardio-metabolic disease risk, it has been suggested that metabolic endotoxemia may serve a key mediator of metabolic derangements observed in obesity. This review provides supporting evidence of mechanistic associations with cell and animal models, and provides complimentary evidence of the clinical relevance of metabolic endotoxemia in obesity as it relates to inflammation and metabolic derangements in humans. Discrepancies with endotoxin detection are considered, and an alternate method of reporting metabolic endotoxemia is recommended until a standardized measurement protocol is set forth. PMID- 26133661 TI - Failure of hippocampal deactivation during loss events in treatment-resistant depression. AB - Major depressive disorder is characterized by anhedonia, cognitive biases, ruminations, hopelessness and increased anxiety. Blunted responses to rewards have been reported in a number of recent neuroimaging and behavioural studies of major depressive disorder. In contrast, neural responses to aversive events remain an under-studied area. While selective serotonergic reuptake inhibitors are often effective in treating major depressive disorder, their mechanism of action remains unclear. Following a series of animal model investigations of depressive illness and serotonergic function, Deakin and Graeff predicted that brain activity in patients with major depressive disorder is associated with an overactive dorsal raphe nucleus with overactive projections to the amygdala, periaqueductal grey and striatum, and an underactive median raphe nucleus with underactive projections to the hippocampus. Here we describe an instrumental loss avoidance and win-gain reinforcement learning functional magnetic resonance imaging study with 40 patients with highly treatment-resistant major depressive disorder and never-depressed controls. The dorsal raphe nucleus/ periaqueductal grey region of the midbrain and hippocampus were found to be overactive in major depressive disorder during unsuccessful loss-avoidance although the median raphe nucleus was not found to be underactive. Hippocampal overactivity was due to a failure to deactivate during loss events in comparison to controls, and hippocampal over-activity correlated with depression severity, self-report 'hopelessness' and anxiety. Deakin and Graeff argued that the median raphe nucleus normally acts to inhibit consolidation of aversive memories via the hippocampus and this system is underactive in major depressive disorder, facilitating the development of ruminations, while the dorsal raphe nucleus system is engaged by distal cues predictive of threats and is overactive in major depressive disorder. During win events the striatum was underactive in major depressive disorder. We tested individual patient consistency of these findings using within-study replication. Abnormal hippocampal activity correctly predicted individual patient diagnostic status in 97% (sensitivity 95%, specificity 100%) of subjects, and abnormal striatal activity predicted diagnostic status in 84% (sensitivity 79%, specificity 89%) of subjects. We conclude that the neuroimaging findings were largely consistent with Deaken and Graeff's predictions, abnormally increased hippocampal activity during loss events was an especially consistent abnormality, and brainstem serotonergic nuclei merit further study in depressive illness. PMID- 26133660 TI - Increased TRPC5 glutathionylation contributes to striatal neuron loss in Huntington's disease. AB - Aberrant glutathione or Ca(2+) homeostasis due to oxidative stress is associated with the pathogenesis of neurodegenerative disorders. The Ca(2+)-permeable transient receptor potential cation (TRPC) channel is predominantly expressed in the brain, which is sensitive to oxidative stress. However, the role of the TRPC channel in neurodegeneration is not known. Here, we report a mechanism of TRPC5 activation by oxidants and the effect of glutathionylated TRPC5 on striatal neurons in Huntington's disease. Intracellular oxidized glutathione leads to TRPC5 activation via TRPC5 S-glutathionylation at Cys176/Cys178 residues. The oxidized glutathione-activated TRPC5-like current results in a sustained increase in cytosolic Ca(2+), activated calmodulin-dependent protein kinase and the calpain-caspase pathway, ultimately inducing striatal neuronal cell death. We observed an abnormal glutathione pool indicative of an oxidized state in the striatum of Huntington's disease transgenic (YAC128) mice. Increased levels of endogenous TRPC5 S-glutathionylation were observed in the striatum in both transgenic mice and patients with Huntington's disease. Both knockdown and inhibition of TRPC5 significantly attenuated oxidation-induced striatal neuronal cell death. Moreover, a TRPC5 blocker improved rearing behaviour in Huntington's disease transgenic mice and motor behavioural symptoms in littermate control mice by increasing striatal neuron survival. Notably, low levels of TRPC1 increased the formation of TRPC5 homotetramer, a highly Ca(2+)-permeable channel, and stimulated Ca(2+)-dependent apoptosis in Huntington's disease cells (STHdh(Q111/111)). Taken together, these novel findings indicate that increased TRPC5 S-glutathionylation by oxidative stress and decreased TRPC1 expression contribute to neuronal damage in the striatum and may underlie neurodegeneration in Huntington's disease. PMID- 26133662 TI - Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies. AB - Congenital myasthenic syndromes are inherited disorders that arise from impaired signal transmission at the neuromuscular junction. Mutations in at least 20 genes are known to lead to the onset of these conditions. Four of these, ALG2, ALG14, DPAGT1 and GFPT1, are involved in glycosylation. Here we identify a fifth glycosylation gene, GMPPB, where mutations cause congenital myasthenic syndrome. First, we identified recessive mutations in seven cases from five kinships defined as congenital myasthenic syndrome using decrement of compound muscle action potentials on repetitive nerve stimulation on electromyography. The mutations were present through the length of the GMPPB, and segregation, in silico analysis, exon trapping, cell transfection followed by western blots and immunostaining were used to determine pathogenicity. GMPPB congenital myasthenic syndrome cases show clinical features characteristic of congenital myasthenic syndrome subtypes that are due to defective glycosylation, with variable weakness of proximal limb muscle groups while facial and eye muscles are largely spared. However, patients with GMPPB congenital myasthenic syndrome had more prominent myopathic features that were detectable on muscle biopsies, electromyography, muscle magnetic resonance imaging, and through elevated serum creatine kinase levels. Mutations in GMPPB have recently been reported to lead to the onset of muscular dystrophy dystroglycanopathy. Analysis of four additional GMPPB associated muscular dystrophy dystroglycanopathy cases by electromyography found that a defective neuromuscular junction component is not always present. Thus, we find mutations in GMPPB can lead to a wide spectrum of clinical features where deficit in neuromuscular transmission is the major component in a subset of cases. Clinical recognition of GMPPB-associated congenital myasthenic syndrome may be complicated by the presence of myopathic features, but correct diagnosis is important because affected individuals can respond to appropriate treatments. PMID- 26133663 TI - Cerebrospinal fluid tau and amyloid-beta1-42 in patients with dementia. AB - Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-beta1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-beta1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-beta1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-beta1-42 and amyloid-beta1 42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-beta1 42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-beta1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with Lewy bodies and Parkinson's disease dementia groups 53%, 34%, 67% and 53% of the subjects, respectively had abnormal amyloid-beta1-42 levels, 41%, 41%, 28% and 28% had abnormal total tau levels, and 29%, 28%, 25% and 19% had abnormal phosphorylated tau levels. Cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels. In addition, cerebrospinal fluid amyloid-beta1 42, total tau, phosphorylated tau and the amyloid-beta1-42:phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-beta1-42 in Parkinson's disease dementia and vascular dementia. The results support the use of cerebrospinal fluid biomarkers to differentiate between dementias in clinical practice, and to estimate disease severity. PMID- 26133664 TI - The improvement of the energy resolution in epi-thermal neutron region of Bonner sphere using boric acid water solution moderator. AB - Bonner sphere is useful to evaluate the neutron spectrum in detail. We are improving the energy resolution in epi-thermal neutron region of Bonner sphere, using boric acid water solution as a moderator. Its response function peak is narrower than that for polyethylene moderator and the improvement of the resolution is expected. The resolutions between polyethylene moderator and boric acid water solution moderator were compared by simulation calculation. Also the influence in the uncertainty of Bonner sphere configuration to spectrum estimation was simulated. PMID- 26133665 TI - Photostimulated luminescence detection and radiation effects on cinnamon (Cinnamomum zeylanicum) spice. AB - The increase of disease borne pathogens in foods has promoted the use of new technologies in order to eliminate these pathogen microorganisms and extend the shelf-life of the foodstuffs. In particular, Cinnamon (Cinnamomum zeylanicum) contains an important number of pathogen microorganisms and it is frequently sterilized by gamma radiation. However, it is important to develop the detection methods for irradiated food in order to keep the dose control and also to analyze the radiation effects in their chemical property. This work reports (i) the photostimulated luminescence (PSL) detection of irradiated cinnamon and thermoluminescence (TL) detection of the inorganic polymineral fraction separated from this spice, and (ii) the proximate chemical analysis carried out on fat, protein and dietetic fiber contents. The detection limits using the PSL and TL methods were 500 Gy and 10 Gy, respectively, and the fat content was increased significantly with the gamma dose that could be related to the lipid oxidation in the cinnamon. PMID- 26133666 TI - Fenofibrate and extended-release niacin improve the endothelial protective effects of HDL in patients with metabolic syndrome. AB - BACKGROUND: Fibrates and niacin are at present the most effective therapies to increase plasma levels of high density lipoprotein-cholesterol (HDL-C); to date, limited data are available on their effects on HDL protective functions. METHODS AND RESULTS: Within a multicenter, randomized, open-label, cross-over study, 37 patients with metabolic syndrome received 6weeks' treatment with fenofibrate or extended-release niacin (ER niacin), with a 4weeks' wash-out period. HDL ability to preserve endothelial cell homeostasis was assessed by incubating cultured endothelial cells with HDL isolated from patients at baseline and after each treatment. HDL isolated from patients at baseline were as effective as control HDL in inhibiting vascular cell adhesion molecule-1 (VCAM-1) expression, but less efficient in promoting endothelial cell nitric oxide (NO) release. Both fenofibrate and ER niacin increased HDL ability to inhibit TNFalpha-induced VCAM 1 expression (+7% and +11%, respectively). Fenofibrate and ER niacin also improved the impaired HDL ability to induce the expression of endothelial nitric oxide synthase and NO production (+10% and +8%, respectively). Interestingly, HDL isolated after treatment showed an ability to promote endothelial NO release similar to HDL isolated from controls. No differences were observed between the two drugs. With both drugs, HDL function was improved irrespective of baseline HDL-C levels. CONCLUSION: Treatment with fenofibrate or ER niacin in patients with metabolic syndrome not only increased HDL-C levels but also improved the endothelial protective effects of HDL. PMID- 26133667 TI - Nature and nurture in atherosclerosis: The roles of acylcarnitine and cell membrane-fatty acid intermediates. AB - Macrophages recycle components of dead cells, including cell membranes. When quantities of lipids from cell membranes of dead cells exceed processing capacity, phospholipid and cholesterol debris accumulate as atheromas. Plasma lipid profiles, particularly HDL and LDL cholesterol, are important tools to monitor atherosclerosis risk. Membrane lipids are exported, as triglycerides or phospholipids, or as cholesterol or cholesterol esters, via lipoproteins for disposal, for re-use in cell membranes, or for fat storage. Alternative assays evaluate other aspects of lipid pathology. A key process underlying atherosclerosis is backup of macrophage fatty acid catabolism. This can be quantified by accumulation of acylcarnitine intermediates in extracellular fluid, a direct assay of adequacy of beta-oxidation to deal with membrane fatty acid recycling. Further, membranes of somatic cells, such as red blood cells (RBC), incorporate fatty acids that reflect dietary intake. Changes in RBC lipid composition occur within days of ingesting modified fats. Since diets with high saturated fat content or artificial trans-fatty acids promote atherosclerosis, RBC lipid content shifts occur with atherosclerosis, and can show cellular adaptation to pathologically stiff membranes by increased long-chain doubly unsaturated fatty acid production. Additional metabolic changes with atherosclerosis of potential utility include inflammatory cytokine production, modified macrophage signaling pathways, and altered lipid-handling enzymes. Even after atherosclerotic lesions appear, approaches to minimize macrophage overload by reducing rate of fat metabolism are promising. These include preventive measures, and drugs including statins and the newer PCSK9 inhibitors. New cell based biochemical and cytokine assays provide data to prevent or monitor atherosclerosis progression. PMID- 26133668 TI - The angiotensin receptor blocker losartan reduces coronary arteriole remodeling in type 2 diabetic mice. AB - Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on coronary microvascular structural remodeling. The renin-angiotensin-aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT1R signaling dictates vascular smooth muscle growth that partially underlies coronary arteriole remodeling in T2DM. Control and db/db mice were given AT1R blocker losartan via drinking water for 4 weeks. Using pressure myography, we found that coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved coronary flow reserve. Our data suggest that Ang II-AT1R signaling mediates, at least in part, coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the coronary microvasculature in T2DM may help reduce cardiac ischemic events. PMID- 26133669 TI - Substrate and stereocontrolled iodocycloetherification of highly functionalized enantiomerically pure allylic alcohols: application to synthesis of cytotoxic 2 epi jaspine B and its biological evaluation. AB - Stereoselectivities of electrophilic additions of molecular iodine to enantiomerically pure highly functionalized allylic alcohols with internal nucleophiles have been investigated. The intramolecular nucleophilic attack on the I2-pi complex by an oxygen nucleophile to obtain tri- and tetrasubstituted THFs is highly regio-, stereoselective and substrate controlled. The application of this study has been shown by utilizing one of the THFs 4a as a key intermediate to complete the total synthesis of marine anti-cancer natural product 2-epi jaspine B. PMID- 26133671 TI - The conjoined twin sisters Helen and Judith (1701-1723) and their pictorial impact in later 18th-century science. AB - Given the uniqueness of the Hungarian conjoined twin sisters Helen and Judith (1701-1723) and their lasting influence as an anatomical showcase if not model for mental or social deviant states, we present here a closer scrutiny of their introduction into the scientific literature of the later 18th century by analyzing depictions of the twins from 1707 onwards. PMID- 26133672 TI - On the importance of a precise crystal structure for simulating gas adsorption in nanoporous materials. AB - We show that simulation of gas adsorption in nanoporous sorbents may be highly sensitive to accurate crystallographic coordinates, even for frameworks anticipated to have low flexibility. PMID- 26133670 TI - The BEACH Domain Protein SPIRRIG Is Essential for Arabidopsis Salt Stress Tolerance and Functions as a Regulator of Transcript Stabilization and Localization. AB - Members of the highly conserved class of BEACH domain containing proteins (BDCPs) have been established as broad facilitators of protein-protein interactions and membrane dynamics in the context of human diseases like albinism, bleeding diathesis, impaired cellular immunity, cancer predisposition, and neurological dysfunctions. Also, the Arabidopsis thaliana BDCP SPIRRIG (SPI) is important for membrane integrity, as spi mutants exhibit split vacuoles. In this work, we report a novel molecular function of the BDCP SPI in ribonucleoprotein particle formation. We show that SPI interacts with the P-body core component DECAPPING PROTEIN 1 (DCP1), associates to mRNA processing bodies (P-bodies), and regulates their assembly upon salt stress. The finding that spi mutants exhibit salt hypersensitivity suggests that the local function of SPI at P-bodies is of biological relevance. Transcriptome-wide analysis revealed qualitative differences in the salt stress-regulated transcriptional response of Col-0 and spi. We show that SPI regulates the salt stress-dependent post-transcriptional stabilization, cytoplasmic agglomeration, and localization to P-bodies of a subset of salt stress-regulated mRNAs. Finally, we show that the PH-BEACH domains of SPI and its human homolog FAN (Factor Associated with Neutral sphingomyelinase activation) interact with DCP1 isoforms from plants, mammals, and yeast, suggesting the evolutionary conservation of an association of BDCPs and P-bodies. PMID- 26133674 TI - Predicting Responses to Bids for Sexual and Romantic Escalation in Cross-Sex Friendships. AB - The transition from a platonic cross-sex friendship to a more intimate sexual and/or romantic relationship is an interesting, yet somewhat understudied, phenomenon. In this study, we introduce and test relationship adaptation theory to predict cross-sex friends' predispositions for reciprocating a bid for escalation to an exclusive dating or friends with benefits (FWB) relationship. Analyses of data collected from 288 participants found participants' dating status, anticipated rewards from escalating the relationship, expected social disapproval, friendship quality, and their friend's attractiveness predicted disposition to reciprocating a cross-sex friend's hypothetical bid for escalation to an exclusive romantic escalation. In addition, participants' biological sex, anticipated rewards from escalating the relationship, expected social disapproval, sexual permissiveness, and their friend's attractiveness emerged as predictors of disposition toward a friend's hypothetical bid to escalate a platonic friendship to a FWB relationship. PMID- 26133673 TI - FGF-2 induces the proliferation of human periodontal ligament cells and modulates their osteoblastic phenotype by affecting Runx2 expression in the presence and absence of osteogenic inducers. AB - The exact phenotype of human periodontal ligament cells (hPDLCs) remains a controversial area. Basic fibroblast growth factor (FGF-2) exhibits various functions and its effect on hPDLCs is also controversial. Therefore, the present study examined the effect of FGF-2 on the growth and osteoblastic phenotype of hPDLCs with or without osteogenic inducers (dexamethasone and beta glycerophosphate). FGF-2 was added to defined growth culture medium and osteogenic inductive culture medium. Cell proliferation, osteogenic differentiation and mineralization were measured. The selected differentiation markers, Runx2, collagen type I, alpha1 (Col1a1), osteocalcin (OCN) and epidermal growth factor receptor (EGFR), were investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Runx2 and OCN protein expression was measured by western blotting. FGF-2 significantly increased the proliferation of hPDLCs, but did not affect alkaline phosphatase activity. RT qPCR analysis revealed enhanced mRNA expression of Runx2, OCN and EGFR, but suppressed Col1a1 gene expression in the absence of osteogenic inducers, whereas all these gene levels had no clear trend in their presence. The Runx2 protein expression was clearly increased, but the OCN protein level showed no evident trend. The mineralization assay demonstrated that FGF-2 inhibited mineralized matrix deposition with osteogenic inducers. These results suggested that FGF-2 induces the growth of immature hPDLCs, which is a competitive inhibitor of epithelial downgrowth, and suppresses their differentiation into mineralized tissue by affecting Runx2 expression. Therefore, this may lead to the acceleration of periodontal regeneration. PMID- 26133675 TI - Spatiotemporal Floral Scent Variation of Penstemon digitalis. AB - Variability in floral volatile emissions can occur temporally through floral development, during diel cycles, as well as spatially within a flower. These spatiotemporal patterns are hypothesized to provide additional information to floral visitors, but they are rarely measured, and their attendant hypotheses are even more rarely tested. In Penstemon digitalis, a plant whose floral scent has been shown to be under strong phenotypic selection for seed fitness, we investigated spatiotemporal variation in floral scent by using dynamic headspace collection, respectively solid-phase microextraction, and analyzed the volatile samples by combined gas chromatography-mass spectrometry. Total volatile emission was greatest during flowering and peak pollinator activity hours, suggesting its importance in mediating ecological interactions. We also detected tissue and reward-specific compounds, consistent with the hypothesis that complexity in floral scent composition reflects several ecological functions. In particular, we found tissue-specific scents for the stigma, stamens, and staminode (a modified sterile stamen common to all Penstemons). Our findings emphasize the dynamic nature of floral scents and highlight a need for greater understanding of ecological and physiological mechanisms driving spatiotemporal patterns in scent production. PMID- 26133676 TI - Phomalactone from a Phytopathogenic Fungus Infecting ZINNIA elegans (ASTERACEAE) Leaves. AB - Zinnia elegans Jacq. plants are infected by a fungus that causes dark red spots with necrosis on leaves, particularly in late spring to the middle of summer in the Mid-South of the United States. This fungal disease causes the leaves to wilt and eventually kills the plant. The fungus was isolated, cultured in potato dextrose broth, and identified as Nigrospora sphaerica by molecular techniques. Two major lactone metabolites (phomalactone and catenioblin A) were isolated from liquid culture of N. sphaerica isolated from Z. elegans. When injected into leaves of Z. elegans, phomalactone caused lesions similar to those of the fungus. The lesion sizes were proportional to the concentration of the phomalactone. Phomalactone, but not catenioblin A, was phytotoxic to Z. elegans and other plant species by inhibition of seedling growth and by causing electrolyte leakage from photosynthetic tissues of both Z. elegans leaves and cucumber cotyledons. This latter effect may be related to the wilting caused by the fungus in mature Z. elegans plants. Phomalactone was moderately fungicidal to Coletotrichum fragariae and two Phomopsis species, indicating that the compound may keep certain other fungi from encroaching into plant tissue that N. sphaerica has infected. Production of large amounts of phomalactone by N. sphaerica contributes to the pathogenic behavior of this fungus, and may have other ecological functions in the interaction of N. sphaerica with other fungi. This is the first report of isolation of catenioblin A from a plant pathogenic fungus. The function of catenioblin A is unclear, as it was neither significantly phyto- nor fungitoxic. PMID- 26133677 TI - WITHDRAWN: Perioperative ketamine for acute postoperative pain. PMID- 26133678 TI - Extent and Location of the Excitatory and Inhibitory Cortical Hand Representation Maps: A Navigated Transcranial Magnetic Stimulation Study. AB - Voluntary muscle action and control are modulated by the primary motor cortex, which is characterized by a well-defined somatotopy. Muscle action and control depend on a sensitive balance between excitatory and inhibitory mechanisms in the cortex and in the corticospinal tract. The cortical locations evoking excitatory and inhibitory responses in brain stimulation can be mapped, for example, as a pre-surgical procedure. The purpose of this study was to find the differences between excitatory and inhibitory motor representations mapped using navigated transcranial magnetic stimulation (nTMS). The representations of small hand muscles were mapped to determine the areas and the center of gravities (CoGs) in both hemispheres of healthy right-handed volunteers. The excitatory representations were obtained via resting motor evoked potential (MEP) mapping, with and without a stimulation grid. The inhibitory representations were mapped using the grid and measuring corticospinal silent periods (SPs) during voluntary muscle contraction. The excitatory representations were larger on the dominant hemisphere compared with the non-dominant (p < 0.05). The excitatory CoGs were more medial (p < 0.001) and anterior (p < 0.001) than the inhibitory CoGs. The use of the grid did not influence the areas or the CoGs. The results support the common hypothesis that the MEP and SP representations are located at adjacent sites. Furthermore, the dominant hemisphere seems to be better organized for controlling excitatory motor functions with respect to TMS. In addition, the inhibitory representations could provide further information about motor reorganization and aid in surgery planning when the functional cortical representations are located in abnormal cortical regions. PMID- 26133679 TI - Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling. AB - Widdrol is an odorous compound derived from Juniperus chinensis that is widely used in traditional medicine to treat fever, inflammation and cancer. It was previously reported that widdrol has antitumor activity by apoptosis induction in cancer cells in vitro. However, its anti-angiogenic activity remains elusive. In the present study, we investigated the anti-angiogenic activity of widdrol and the molecular mechanisms involved. Widdrol inhibited cell proliferation via G1 phase arrest induction in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Additionally, it was associated with a decreased expression of cyclin-dependent kinase 2 (CDK2) and an increased expression of p21, a CDK inhibitor. Widdrol significantly inhibited the cell migration and tube formation of HUVECs using an in vitro angiogenesis assay. The results showed that widdrol suppressed phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream proteins, such as AKT, focal adhesion kinase (FAK) and endothelial nitric oxide synthase (eNOS). Moreover, widdrol effectively reduced tumor growth and blood vessel formation in colon tumor xenograft mice. Collectively, these results suggested that widdrol may act as a potential anti angiogenic agent by inhibiting vessel sprouting and growth, which may have implications for angioprevention. PMID- 26133686 TI - A new Keggin-like niobium-phosphate cluster that reacts reversibly with hydrogen peroxide. AB - Polyoxoniobate clusters that are stable in acidic solutions are rare and particularly useful in industrial processes. Here we report a new pentaphosphate niobate polyoxometalate cluster (TMA)9H3Nb9P5O41.28H2O (Nb9P5) that is stable over a wide pH range and that can be converted reversibly into the peroxo form. PMID- 26133680 TI - Serum Albumin Binding Inhibits Nuclear Uptake of Luminescent Metal-Complex-Based DNA Imaging Probes. AB - The DNA binding and cellular localization properties of a new luminescent heterobimetallic Ir(III) Ru(II) tetrapyridophenazine complex are reported. Surprisingly, in standard cell media, in which its tetracationic, isostructural Ru(II) Ru(II) analogue is localized in the nucleus, the new tricationic complex is poorly taken up by live cells and demonstrates no nuclear staining. Consequent cell-free studies reveal that the Ir(III) Ru(II) complex binds bovine serum albumin, BSA, in Sudlow's Site I with a similar increase in emission and binding affinity to that observed with DNA. Contrastingly, in serum-free conditions the complex is rapidly internalized by live cells, where it localizes in cell nuclei and functions as a DNA imaging agent. The absence of serum proteins also greatly alters the cytotoxicity of the complex, where high levels of oncosis/necrosis are observed due to this enhanced uptake. This suggests that simply increasing the lipophilicity of a DNA imaging probe to enhance cellular uptake can be counterproductive as, due to increased binding to serum albumin protein, this strategy can actually disrupt nuclear targeting. PMID- 26133687 TI - Velocity statistics of dynamic spinners in out-of-equilibrium magnetic suspensions. AB - We report on the velocity statistics of an out-of-equilibrium magnetic suspension in a spinner phase confined at a liquid interface. The suspension is energized by a uniaxial alternating magnetic field applied parallel to the interface. In a certain range of the magnetic field parameters the system spontaneously undergoes a transition into a dynamic spinner phase (ensemble of hydrodynamically coupled magnetic micro-rotors) comprised of two subsystems: self-assembled spinning chains and a gas of rotating single particles. Both subsystems coexist in a dynamic equilibrium via continuous exchange of the particles. Spinners excite surface flows that significantly increase particle velocity correlations in the system. For both subsystems the velocity distributions are strongly non Maxwellian with nearly exponential high-energy tails, P(v) ~ exp(-|v/v0|). The kurtosis, the measure of the deviation from the Gaussian statistics, is influenced by the frequency of the external magnetic field. We show that in the single-particle gas the dissipation is mostly collisional, whereas the viscous damping dominates over collisional dissipation for the self-assembled spinners. The dissipation increases with the frequency of the applied magnetic field. Our results provide insights into non-trivial dissipation mechanisms determining self assembly processes in out-of-equilibrium magnetic suspensions. PMID- 26133688 TI - Increases in the longevity of desiccation-phase developing rice seeds: response to high-temperature drying depends on harvest moisture content. AB - BACKGROUND AND AIMS: Previous studies have suggested that the drying conditions routinely used by genebanks may not be optimal for subsequent seed longevity. The aim of this study was to compare the effect of hot-air drying and low-temperature drying on subsequent seed longevity for 20 diverse rice accessions and to consider how factors related to seed production history might influence the results. METHODS: Seeds of rice, Oryza sativa, were produced according to normal regeneration procedures at IRRI. They were harvested at different times [harvest date and days after anthesis (DAA), once for each accession] and dried either in a drying room (DR; 15 % relative humidity, 15 degrees C) or in a flat-bed heated air batch dryer (BD; 45 degrees C, 8 h d(-1)) for up to six daily cycles followed by drying in the DR. Relative longevity was assessed by storage at 10.9 % moisture content and 45 degrees C. KEY RESULTS: Initial drying in the BD resulted in significantly greater longevity compared with the DR for 14 accessions (seed lots): the period of time for viability to fall to 50 % for seeds dried in the BD as a percentage of that for seeds dried throughout in the DR varied between 1.3 and 372.2 % for these accessions. The seed lots that responded the most were those that were harvested earlier in the season and at higher moisture content. Drying in the BD did not reduce subsequent longevity compared with DR drying for any of the remaining accessions. CONCLUSIONS: Seeds harvested at a moisture content where, according to the moisture desorption isotherm, they could still be metabolically active (>16.2 %) may be in the first stage of the post-mass maturity, desiccation phase of seed development and thus able to increase longevity in response to hot-air drying. The genebank standards regarding seed drying for rice and, perhaps, for other tropical species should therefore be reconsidered. PMID- 26133689 TI - Climate warming could increase recruitment success in glacier foreland plants. AB - BACKGROUND AND AIMS: Glacier foreland plants are highly threatened by global warming. Regeneration from seeds on deglaciated terrain will be crucial for successful migration and survival of these species, and hence a better understanding of the impacts of climate change on seedling recruitment is urgently needed to predict future plant persistence in these environments. This study presents the first field evidence of the impact of climate change on recruitment success of glacier foreland plants. METHODS: Seeds of eight foreland species were sown on a foreland site at 2500 m a.s.l., and at a site 400 m lower in altitude to simulate a 2.7 degrees C increase in mean annual temperature. Soil from the site of origin was used to reproduce the natural germination substrate. Recruitment success, temperature and water potential were monitored for 2 years. The response of seed germination to warming was further investigated in the laboratory. KEY RESULTS: At the glacier foreland site, seedling emergence was low (0 to approx. 40 %) and occurred in summer in all species after seeds had experienced autumn and winter seasons. However, at the warmer site there was a shift from summer to autumn emergence in two species and a significant increase of summer emergence (13-35 % higher) in all species except two. Survival and establishment was possible for 60-75 % of autumn-emerged seedlings and was generally greater under warmer conditions. Early snowmelt in spring caused the main ecological factors enhancing the recruitment success. CONCLUSIONS: The results suggest that warming will influence the recruitment of glacier foreland species primarily via the extension of the snow-free period in spring, which increases seedling establishment and results in a greater resistance to summer drought and winter extremes. The changes in recruitment success observed here imply that range shifts or changes in abundance are possible in a future warmer climate, but overall success may be dependent on interactions with shifts in other components of the plant community. PMID- 26133690 TI - Global 5-methylcytosine alterations in DNA during ageing of Quercus robur seeds. AB - BACKGROUND AND AIMS: Epigenetic regulation plays an important role in the management of plant growth, development and response to stress factors, and several reports have indicated that DNA methylation plays a critical role in seed development and viability. This study examines changes in 5-methylcytosine (m(5)C) levels in the DNA of seeds during ageing, a process that has important implications for plant conservation and agriculture. METHODS: Changes in the global level of m(5)C were measured in mature seeds of oak, Quercus robur. The extent of DNA methylation was measured using a protocol based on two-dimensional thin-layer chromatography. Viability of seeds was determined by germination and seedling emergence tests. KEY RESULTS: An ageing-related decrease in total m(5)C during storage of recalcitrant seeds was highly and significantly correlated with a decrease in seed viability, as reflected by a reduction in germination (r = 0.8880) and seedling emergence (r = 0.8269). CONCLUSIONS: The decrease in viability during ageing of Q. robur seeds is highly correlated with a global decline in the amount of m(5)C in genomic DNA, and it is possible that this may represent a typical response to ageing and senescence in recalcitrant seeds. Potential mechanisms that drive changes in genomic DNA methylation during ageing are discussed, together with their implications for seed viability. PMID- 26133691 TI - Programmed death-ligand 1, 2 expressions are decreased in the psoriatic epidermis. AB - Psoriatic keratinocytes are one of the key components that amplify and maintain chronic inflammation. We hypothesized that lack of proper regulatory functions of keratinocytes can be responsible for chronic inflammation in psoriasis. Programmed death-ligands (PD-L) 1, 2 are expressed on keratinocytes, and expressions by nonlymphoid cells are important for mediating peripheral T cell tolerance. In our study, we investigated whether PD-L1, 2 expressions are altered in keratinocytes of psoriatic epidermis compared to normal epidermis. Epidermis was separated and analyzed for PD-L1, 2 expressions in mRNA and protein levels. Immunohistochemical stainings were done in skin biopsy samples from psoriasis, normal skin, allergic contact dermatitis (ACD), pityriasis rosea (PR) and lichen planus (LP). Expressions of PD-L1, 2 mRNA levels were significantly decreased in psoriatic epidermis compared to normal epidermis. In protein levels, PD-L1 expression was significantly decreased in psoriatic epidermis. However, PD-L2 expression was not detected in both normal and psoriatic epidermis. Immunohistochemical stainings revealed significantly less PD-L1 expression in psoriatic epidermis compared to normal epidermis. Even compared to other cutaneous inflammatory diseases, psoriatic epidermis showed less expression than ACD, PR and LP. PD-L2 expression was minimally detected in normal epidermis and not in psoriatic epidermis, but its expression was increased in ACD, PR and LP. In conclusion, we demonstrated that PD-L1, 2 are decreased in psoriatic epidermis in mRNA and protein levels. In addition, we showed that their expression was significantly lower than other inflammatory skin diseases. We suggest that decreased expression of PD-L1, 2 on psoriatic epidermis can contribute to its chronic unregulated inflammatory characteristics. PMID- 26133692 TI - Sound Production Treatment: Synthesis and Quantification of Outcomes. AB - PURPOSE: This investigation was designed to provide a quantification and synthesis of a series of single-case experimental design investigations into the effects of sound production treatment, an articulatory-kinematic treatment for acquired apraxia of speech (AOS). The main purpose was to perform a meta-analysis of aggregated sound production treatment data in order to provide benchmarks to serve as indicators of magnitude of change. Additional analyses explored various factors influencing effect sizes and level of performance. METHOD: Effect sizes were calculated for treated and untreated items for 24 participants across 10 investigations. Benchmarks were calculated as the quartiles of the distributions of the effect sizes. Correlational analyses were performed to examine (a) end-of treatment performance relative to follow-up performance, (b) response of trained items relative to untrained items, and (c) effect size relative to participant variables. RESULTS: Effect sizes were predominantly large and positive; benchmarks for treated items were larger than those for untreated items. End of treatment and follow-up performance were positively correlated, and response generalization was positively correlated with AOS severity. CONCLUSION: These benchmarks may assist in evaluating the effects of interventions for individuals with AOS utilizing similar outcome measures in both clinical and research settings. PMID- 26133693 TI - Morita-Baylis-Hillman adduct derivatives (MBHADs): versatile reactivity in Lewis base-promoted annulation. AB - Lewis base-promoted annulation reactions with MBHADs have emerged as a key platform for the construction of functionalized carbo- and heterocycles. MBHADs, which are economical and readily available, exert diverse and amazing reactivity when reacted with a wide range of electrophiles. A variety of carbo- and heterocycles, most of which are predominant in natural products and pharmaceuticals, could be constructed with high efficiency. This tutorial review will describe these annulation reactions, with a special emphasis on recent work regarding diverse reactivities of MBHADs. PMID- 26133694 TI - C3G (RapGEF1), a regulator of actin dynamics promotes survival and myogenic differentiation of mouse mesenchymal cells. AB - RapGEF1 (C3G) is a ubiquitously expressed protein that is essential for mammalian embryonic development. We have shown earlier that C3G regulates cytoskeletal dynamics and is required for neuronal differentiation. To determine if C3G plays a wider role in differentiation of multiple tissue types, we examined its role in skeletal muscle differentiation using the model system of C2C12 cells in culture. C3G protein is highly expressed in mouse skeletal muscle and its transcript and protein levels increase as C2C12 cells are induced to differentiate. Increase in C3G was predominantly seen in the nuclei of myotubes. Ectopic expression of C3G promoted myotube formation when cells were cultured in growth as well as differentiation medium and, enhanced MHC levels were associated with C3G expression. C3G induced differentiation required its catalytic and protein interaction domains and was dependent on the function of cellular R-Ras. Knockdown of cellular C3G using small hairpin RNA reduced expression of muscle specific markers and beta-catenin, resulting in impaired differentiation. Disabling C3G function also resulted in enhanced cell death suggesting that cellular C3G is required for cell survival. In cells grown in growth medium, over expressed C3G increased Akt activity, and C3G knockdown reduced it. C3G expression also suppressed cyclin D1 levels, and induced p27 expression, molecules involved in regulating cell proliferation. Endogenous C3G localizes to focal adhesions in myotubes and C3G expressing cells show distinct stress fibers, elongation and parallel alignment. Expression of a dominant negative construct of C3G, disrupts actin cytoskeleton and formation of focal adhesions resulting in detachment of cells from the substratum and inhibition of differentiation. Our results provide evidence that C3G plays an important role in myogenic differentiation by coordinating cell cycle exit, actin dynamics and survival signaling. PMID- 26133695 TI - Preface - The special issue on mitophagy. PMID- 26133696 TI - One-step electrochemical synthesis of ultrathin graphitic carbon nitride nanosheets and their application to the detection of uric acid. AB - Ultrathin graphitic carbon nitride nanosheets (g-C3N4) with a thickness of about 2 nm were synthesized by a one-step electrochemical method for the first time. The possible mechanism of the electrochemical synthesis was discussed. This as synthesized g-C3N4 showed intrinsic peroxidase-like activity and was successfully applied for the detection of uric acid. PMID- 26133697 TI - Influence of adjuvants on the dissipation of fenpropimorph, pyrimethanil, chlorpyrifos and lindane on the solid/gas interface. AB - The use of pesticides is an integral part of modern agriculture and contributes to the productivity and the quality of the cultivated crop. However, use of pesticides imposes a huge burden on the environment. Volatilisation of pesticides contaminates the environment, affects nearby crops, bystanders and residents but research to mitigate this environmental contamination remains scarce. In this study, the use of adjuvants to reduce the volatilisation and mitigate the environmental contamination was investigated. Dissipation of fenpropimorph, pyrimethanil, chlorpyrifos-ethyl and lindane as pure active ingredient, formulated by different adjuvants and in a commercial formulation were studied. An empirical model assuming exponential decay of the volatilisation rate was used to calculate the volatilisation. In 48 h, up to 90% of the pure fenpropimorph and lindane volatilised. Addition of adjuvants was shown to reduce the volatilisation of pesticides by up to 80%. Commercial formulation was able to reduce the volatilisation of pyrimethanil but the formulation of fenpropimorph had no effect on its volatilisation. PMID- 26133698 TI - Sorption of Cu and Zn in low organic matter-soils as influenced by soil properties and by the degree of soil weathering. AB - Copper and Zn sorption and desorption, among other factors, depend on soil pH, but in soils with different degree of weathering the role of other soil properties (e.g., oxides content and the level of their crystallinity) has not been thoroughly examined. We conducted batch sorption and desorption tests using 21 low-organic C soils that belonged to the soil orders of Entisols, newly developed soils, Inceptisols, and Alfisols, the most weathered soils. Zinc sorption was lower than that of Cu, and its desorption faster, confirming that it is a highly mobile metal. Alfisols had the weaker affinity for metals, due to the lower soil pH typical of this soil order, but also due to the low reactivity colloids they contained. Correlation analyses showed that Fe oxides in Alfisols increased metal release from soils, while they decreased metal desorption from Entisols. We conclude that in low organic matter-content soils, where the protective role of organic colloids is not to be expected, high soil pH alone is not sufficient to protect against metal contamination, but the degree of soil weathering is also important, due to the dominant role of other mineral phases (here, Fe oxides). PMID- 26133699 TI - Subcellular distribution and chemical forms of cadmium in Impatiens walleriana in relation to its phytoextraction potential. AB - Impatiens (Impatiens walleriana) has been shown to be a potential cadmium (Cd) hyperaccumulator, but its mechanisms in accumulation and detoxification have not been reported. Rooted cuttings of Impatiens were planted in artificially Cd contaminated soils for 50 days with total target concentrations of 0, 10, 20, 40, 80, and 120 mg/kg. The subcellular distribution and chemical forms of Cd in the different organs were analyzed after the pot experiment. Compared with the control group, various Cd treatments affected the growth exhibitions of Impatiens, but most of them were not statistically significant. The Cd accumulation of different organs increased with an increase in the soil Cd concentrations for most of the treatments, and it was in the decreasing order of root>stem>leaf. In the roots of Impatiens, Cd was mainly compartmentalized in the soluble fraction (Fs), which has a high migration capacity and will further translocate to the shoot. The Cd was mainly compartmentalized in the cell wall fraction (Fcw) in the shoots as a mechanism of tolerance. Most of the Cd in the various organs of Impatiens was mainly in the forms of pectate and protein integrated (FNaCl), whereas a minor portion was a water soluble fraction (FW). The experimental results show that the Cd in the Fs, FW, and FNaCl in the roots of Impatiens had a high mobility and will further translocate to the shoot. They could be used to estimate the Cd accumulated in the shoots of Impatiens. PMID- 26133700 TI - Facile sonochemical synthesis of pH-responsive copper nanoclusters for selective and sensitive detection of Pb(2+) in living cells. AB - A one-pot sonochemical reaction of Cu(NO3)2 with glutathione (GSH), the latter functioning as a reducing agent and a stabilizing agent, rapidly affords Cu nanoclusters (NCs). The as-prepared GSH-CuNCs possess a small size (~2.2 +/- 0.2 nm), red luminescence with quantum yield (5.3%), and water-dispersibility. Moreover, the fluorescence of the as-prepared GSH-CuNCs is responsive to pH so that the intensity of fluorescence increases rapidly with decreasing pH from 9 to 4. Besides, the GSH-CuNCs would be aggregated by Pb(2+) ions in aqueous solution which results in quenching of the fluorescence. Therefore, such GSH-CuNCs would be excellent candidates as fluorescent probes for the label-free detection of Pb(2+) with the limit of detection at 1.0 nM. Importantly, CAL-27 cells are used as models to achieve potential application as probes for monitoring Pb(2+) in living cells. Thus, these fluorescent CuNCs could work as an alternative to conventional fluorescent probes for biolabeling, sensing and other applications. PMID- 26133701 TI - Purinergic Signaling Is a Novel Mechanism of the Cellular Response to Ionizing Radiation. AB - Recent studies suggest the effect of radiation is observed not only in irradiated cells but also in adjacent non-irradiated cells (bystander effect), although the mechanism has not yet been fully revealed. This bystander effect may be caused by intercellular communication via a gap junction or by messengers released from irradiated cells, such as reactive oxygen species, nitric oxide, or cytokines. However, an unknown mechanism is also possible in the bystander effect. On the other hand, it is known that extracellular ATP, ADP, uridine 5'-triphosphate (UTP), and uridine 5'-diphosphate (UDP), which are released from cells, act as intercellular signaling molecules by activating purinergic P2X and P2Y receptors (purinergic signaling). Recently, I have suggested these extracellular nucleotides may be novel mediators of a radiation-induced bystander effect, because our recent studies indicated that purinergic signaling is involved in important cellular responses to radiation. Our data indicate that ionizing irradiation causes activation of the transient receptor potential melastatin type 2 (TRPM2) channel, and then ATP is released from cells through the anion channel or connexin43 hemichannel mediated by the activation of a P2X7 receptor. The released nucleotides activate P2Y6 and P2Y12 receptors, which are involved in the DNA damage response after irradiation. Activation of the P2Y6 receptor is also involved in radiation-induced activation of the epithelial growth factor receptor extracellular signal regulated protein kinase (EGFR-ERK)1/2 pathway and subsequent nuclear translocation of EGFR, which plays a role in DNA repair. Further, the induction of an antioxidant after irradiation is also mediated by the activation of the P2Y receptor. In conclusion, purinergic signaling could play an important role in the protective cellular response to ionizing irradiation. PMID- 26133702 TI - Foreword. PMID- 26133703 TI - Modulation of Cell Death and Survival by Adipokines in the Liver. AB - Adipokines, hormones predominantly produced from adipose tissue, have been shown to impart dynamic functions in the liver. Emerging evidence has shown that adipokines are also involved in modulating liver cell survival and/or death. Among the various adipokines, adiponectin and leptin directly regulate proliferation of hepatocytes, Kupffer cells, and hepatic stellate cells. Moreover, these adipokines control apoptosis and cell cycle of hepatic cancer cells in a complex manner. Adiponectin possesses both pro- and anti-proliferative properties, whereas leptin appears to play roles as a pro-survival hormone. Recent studies have revealed that regulation of cell death and proliferation is one of the critical factors regulating liver physiology by adipokines. In this review, we summarize the effects of adipokines on apoptosis and survival of liver cells and also demonstrate their implications in regulating various liver functions and decipher the underlying molecular mechanisms. PMID- 26133704 TI - Sestrin2: A Promising Therapeutic Target for Liver Diseases. AB - Sestrin2 (Sesn2), a highly conserved antioxidant protein, is induced by various stresses, including oxidative and energetic stress, and protects cells against those stresses. In normal physiological conditions, redox-homeostasis plays an essential role in cell survival and performs the cellular functions to protect the cells against oxidative damage. The liver is susceptible to oxidative stress, since it is responsible for xenobiotic detoxification and energy metabolism. For this reason, oxidative stress is associated with the pathogenesis of liver diseases. Recently, the role of Sesn2 has been investigated in liver injury and related diseases. In this paper, we review the role of Sesn2 in the pathophysiology of liver diseases and the potential clinical applications of Sesn2 as a therapeutic target to prevent/treat liver diseases. This article promotes our understanding of liver disease progression and advances the development of strategies for pharmacological intervention. PMID- 26133705 TI - Metabolism of Sulfur-Containing Amino Acids in the Liver: A Link between Hepatic Injury and Recovery. AB - Methionine is an essential sulfur-containing amino acid that is metabolized mainly in the liver, where it is converted to S-adenosylmethionine (SAM) by methionine adenosyltransferase. Importantly, SAM is a metabolically pleiotropic molecule that participates in three types of biochemical reactions; transmethylation, transsulfuration (which results in the transfer of sulfur from methionine to serine to form cysteine), and amino propylation (to synthesize polyamines). Critical roles of SAM in the liver have been extensively studied using transgenic animals with chronically reduced or increased hepatic SAM levels. Interestingly, both models with abnormal hepatic SAM concentrations develop liver disease suggesting that SAM homeostasis plays a pivotal role in liver disease. The transsulfuration pathway is connected to the production of glutathione (GSH), which has potent antioxidant capacity in the liver. Accumulating data show that GSH depletion renders the liver vulnerable to oxidative stress and prone to progression of liver disease. In this review, we highlight the importance of homeostasis in the metabolism of sulfur-containing amino acids with a particular focus on the transsulfuration pathway which could be a promising therapeutic target in liver injury. PMID- 26133706 TI - Peptidyl-Prolyl cis/trans Isomerase NIMA-Interacting 1 as a Therapeutic Target in Hepatocellular Carcinoma. AB - Phosphorylation of proteins on serine or threonine residues preceding proline is a pivotal signaling mechanism regulating cell proliferation. The recent identification and characterization of the enzyme peptidyl-prolyl cis/trans isomerase never in mitosis A (NIMA)-interacting 1 (PIN1) has led to the discovery of a new mechanism regulating phosphorylation in cell signaling. PIN1 specifically binds phosphorylated serine or threonine residues immediately preceding proline (pSer/Thr-Pro) and then regulates protein functions, including catalytic activity, phosphorylation status, protein interactions, subcellular location, and protein stability, by promoting cis/trans isomerization of the peptide bond. Recent results have indicated that such conformational changes following phosphorylation represent a novel signaling mechanism in the regulation of many cellular functions. Understanding this mechanism also provides new insight into the pathogenesis and treatment of human hepatocellular carcinoma. A better understanding of the role of PIN1 in the pathogenesis of hepatocellular carcinoma may lead to the identification of molecular targets for prevention and therapeutic intervention. PMID- 26133707 TI - Differential Roles of Angiogenesis in the Induction of Fibrogenesis and the Resolution of Fibrosis in Liver. AB - Liver fibrosis is a wound healing process that includes inflammation, deposition of extracellular matrix molecules, and pathological neovascularization. Angiogenesis, which is defined by the formation of new blood vessels from pre existing vessels, is a complex and dynamic process under both physiological and pathological conditions. Although whether angiogenesis can induce or occur in parallel with the progression of hepatic fibrosis has not yet been determined, intrahepatic sinusoidal formation and remodeling are key features of liver fibrosis. Some recent evidence has suggested that experimental inhibition of angiogenesis ameliorates the development of liver fibrosis, while other recent studies indicate that neutralization or genetic ablation of vascular endothelial growth factor (VEGF) in myeloid cells can delay tissue repair and fibrosis resolution in damaged liver. In this review, we briefly summarize the current knowledge about the differential roles of angiogenesis in the induction of fibrogenesis and the resolution of fibrosis in damaged livers. Possible strategies for the prevention and treatment of liver fibrosis are also discussed. PMID- 26133708 TI - Molecular Targeted Therapy for Hepatocellular Carcinoma: Present Status and Future Directions. AB - Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most lethal neoplasm, causing an estimated 700000 deaths annually. Currently HCC has only one systemic molecular targeted therapy, the multi-kinase inhibitor, sorafenib. The standard-of-care for advanced liver cancer is limited because sorafenib can expand the median life expectancy of patients for only 1 year. Thus there is an urgent need to develop a novel molecular targeted therapy to improve therapeutic outcomes for HCC. HCCs are phenotypically and genetically heterogeneous tumors driven by diverse molecular mechanisms. However, HCCs exhibit certain common traits selected through genetic and epigenetic alterations. The identification of common molecular alterations may provide an opportunity to develop more effective anticancer treatment through targeted therapy. Recent studies in liver cancer biology have revealed a limited number of molecular targets responsible for initiating and maintaining dysregulated cell proliferation, including vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), c-mesenchymal-epithelial transition factor-1 (c-Met), mammalian target of rapamycin (mTOR) and histone deacetylases (HDACs). New treatments involving inhibitors targeting several of these critical pathways are in development. This review describes the current understanding of target pathways, ongoing clinical trials using HCC-targeted agents, and future directions in the treatment of HCC. PMID- 26133709 TI - Time-Dependent Inhibition of hOAT1 and hOAT3 by Anthraquinones. AB - We previously showed that anthraquinones (including rhein, emodin, aloe-emodin, chrysophanol and physcion) were inhibitors of human organic anion transporter 1 (hOAT1) and hOAT3, causing transporter-mediated drug-drug interactions in rats. In this study, the time-dependent inhibition (TDI) of hOAT1 and hOAT3 by anthraquinones was investigated. Madin-Darby canine kidney (MDCK)-hOAT1, HEK293 hOAT3 and their parental cells were used. Preincubation with chrysophanol or physcion for 30 min significantly increased the inhibition of hOAT1, but preincubation with rhein, emodin, aloe-emodin or probenecid had no effect on hOAT1 activity. By contrast, preincubation of hOAT3 with emodin, aloe-emodin, chrysophanol or physcion for 30 min significantly increased its inhibition, but preincubation with rhein or probenecid had no effect on activity. As the incubating time lengthened, from 0 to 60 min, both the inhibition of hOAT1 by chrysophanol and physcion and the inhibition of hOAT3 by emodin, aloe-emodin, chrysophanol and physcion were observed to increase in a time-dependent manner. In conclusion, our results suggest that some anthraquinones contribute to the TDI of hOAT1 and hOAT3. An inhibition study without the preincubation procedure may underestimate the inhibitory potential of anthraquinones against hOAT1 and hOAT3. The underlying mechanisms of TDI of hOAT1 and hOAT3 need to be further investigated. PMID- 26133710 TI - Population Pharmacokinetics in China: The Dynamics of Intravenous Voriconazole in Critically Ill Patients with Pulmonary Disease. AB - Pharmacokinetic research in China on the use of voriconazole in critically ill adult patients with different pulmonary diseases remains to be explored. This study evaluated the population pharmacokinetics of the use of voriconazole (VRC) in critically ill patients to determine covariate effects on VRC pharmacokinetics by NONMEM, which could further optimize VRC dosing in this population. A one compartment model with first-order absorption and elimination best fit the data, giving 4.28 L/h clearance and 93.4 L volume of distribution of VRC. The model variability, described as an approximate percentage coefficient of interindividual variability in clearance and volume of distribution, was 72.94% and 26.50%, respectively. A significant association between Cmin and drug response or grade 2 hepatotoxicity was observed (p=0.002, <0.001, respectively, 1.5-4.0 ug/mL) via logistic multivariate regression. Monte Carlo simulations at 100, 150, 200, and 250 mg dosage predicted effectiveness at 45.99%, 99.76%, 98.76%, and 67.75% within the 1.5-4.0 ug/mL range, suggesting that a 150 or 200 mg intravenous dose twice daily is best suited to achieve the target steady state trough concentration range in critically ill patients with pulmonary disease. PMID- 26133711 TI - The Effect of 1 ug/kg Dexmedetomidine Combined with High-Volume/Low-Concentration Caudal Ropivacaine in Children Undergoing Ambulatory Orchiopexy. AB - When local anesthetics are used, the administration of dexmedetomidine (DEX) can prolong analgesic duration. However, the effect of caudal DEX on high volume/low concentration (HVLC) local anesthetics has not been studied. We investigated the analgesic effect of DEX added to a HVLC of ropivacaine for caudal block in children. Eighty children (the American Society of Anesthesiologists (ASA) status I; age, 1-6 years) undergoing ambulatory orchiopexy were enrolled in the study. Children were randomly assigned to undergo a caudal block with 1.5 mL/kg of 0.15% ropivacaine and either 1 ug/kg of DEX (DEX group, n=40) or the same amount of saline (Control group, n=40) under general anesthesia. The results showed that the time to first analgesic request was significantly longer in the DEX group than in the control group. The sevoflurane requirement for anesthesia and frequency of emergence agitation (EA) were also significantly lower in the DEX group. There was no difference in adverse events between the two groups. In conclusion, a dose of 1 ug/kg of caudal DEX prolonged the first analgesic request time, although the immediate postoperative pain scores were comparable in both groups. Furthermore, caudal DEX significantly reduced the sevoflurane requirement and the frequency of EA. PMID- 26133712 TI - Reduced Food-Effect on Intestinal Absorption of Dronedarone by Self microemulsifying Drug Delivery System (SMEDDS). AB - The oral absorption of dronedarone (DRN), a benzofuran derivative with anti arrhythmic activity, is significantly affected by food intake. The absolute bioavailability of the marketed product (Multaq, Sanofi, U.S.) was about 4% without food, but increased to 15% when administered with a high fat meal. Therefore, to reduce the food-effect on the intestinal absorption of DRN, a novel self-microemulsifying drug delivery system (SMEDDS) was formulated and the comparative in vivo absorption studies with the marketed product were carried out using male beagle dogs either in the fasted or fed state. The SMEDDS consisted of the drug, Labrafil M 1944CS, and Kolliphor EL in a weight ratio of 1 : 1 : 2, rapidly formed a fine oil-in-water emulsion with a droplet size less than 50 nm. An in vivo absorption study revealed that the area-under-curve (AUC0-24 h) and maximal plasma concentration (Cmax) were 10.4-fold (p<0.05) and 8.6-fold (p<0.05) higher, respectively, after the marketed product was orally administered to beagles in the fed state when compared to those in the fasted state. This food effect were remarkably alleviated by SMEDDS formulation, with AUC0-24 h and Cmax 2.9-fold (p<0.05) and 2.6-fold (p<0.05) higher in the fed state when compared to the fasted state, by facilitating intestinal absorption of DRN in the fasted state. The results of this study suggest that SMEDDS may decrease the differences in oral absorption of DRN between the prandial states, improving therapeutic efficacy as well as patient compliance. PMID- 26133713 TI - Clopidogrel Napadisilate Monohydrate Loaded Surface-Modified Solid Dispersion: Physicochemical Characterization and in Vivo Evaluation. AB - To develop a novel solid dispersion of clopidogrel napadisilate monohydrate (CNM) with improved stability and oral bioavailability, surface-modified solid dispersions were prepared by spray-drying using water as a solvent, Tween 80 as a surfactant, and hydroxypropylmethyl cellulose (HPMC) as a hydrophilic polymer, and optimized according to drug solubility. Its solid-state characterization was evaluated by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The stability study was performed at 50 degrees C/75% RH over a period of 6 weeks. Its dissolution profiles and oral bioavailability in rats were also compared with that of CNM and clopidogrel bisulfate (CB). The solid dispersion, composed of CNM/HPMC/Tween80 at a weight ratio of 10/2.5/2.5, in which CNM was in the crystalline state, increased the drug solubility approximately 4.6-fold. It showed a significantly better dissolution profile than that of CNM in all the dissolution media, and gave either similar or higher dissolution compared to that of CB. This solubility and dissolution enhancement was attributed to improved wetting and solubilization of CNM crystals due to hydrophilic carriers attached on the drug surface. It had excellent stability, thereby addressing the stability problem of CB powder. Furthermore, it increased the area under curve (AUC) values by about 4-fold and 1.6-fold compared to CNM and CB, respectively, suggesting that it improved the oral bioavailability of the drug in rats. Thus, this solid dispersion system prepared with water, HPMC and Tween 80 can be used to enhance the bioavailability of CNM as well as to solve the stability problem of CB. PMID- 26133714 TI - Synthesis and Antibacterial Activity of Novel Pleuromutilin Derivatives. AB - In this study we describe the design, synthesis, and antibacterial activity of novel pleuromutilin analogs. A series of new compounds containing piperazine and alkylamino or arylamino groups was synthesized. The new compounds were characterized via (1)H-NMR, (13)C-NMR, Fourier transform (FT)-IR and MS, and were further evaluated for their in vitro activity against seven Gram-positive, and one Gram-negative, pathogens. Antibacterial data revealed that all compounds exhibited moderate to good antibacterial activities against sensitive Gram positive pathogens. Specifically, 9d displayed the best activity: its activity to Staphylococcus aureus (ATCC25923) is 0.125 ug/mL, which is equal to the control compound tiamulin. The antibacterial activities of 9d to Streptococcus suis (minimum inhibitory concentration (MIC) of 2 ug/mL), Streptococcus agalactiae (MIC of 0.5 ug/mL), and Streptococcus dysgalactiae (MIC of 0.5 ug/mL) were also excellent compared with the control drug erythromycin (MIC of >128 ug/mL). The binding modes of these compounds with active sites were calculated using the programs of Molecular Operating Environment (MOE) and Pymol. PMID- 26133715 TI - Serum Metabolomics in Rats after Acute Paraquat Poisoning. AB - Paraquat is one of the most widely used herbicides in the world and is highly toxic to humans and animals. In this study, we developed a serum metabolomic method based on GC/MS to evaluate the effects of acute paraquat poisoning on rats. Pattern recognition analysis, including both principal component analysis and partial least squares-discriminate analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the level of octadecanoic acid, L-serine, L-threonine, L-valine, and glycerol in the acute paraquat poisoning group (36 mg/kg) increased, while the levels of hexadecanoic acid, D-galactose, and decanoic acid decreased. These findings provide an overview of systematic responses to paraquat exposure and metabolomic insight into the toxicological mechanism of paraquat. Our results indicate that metabolomic methods based on GC/MS may be useful to elucidate the mechanism of acute paraquat poisoning through the exploration of biomarkers. PMID- 26133716 TI - Hypercalcemia Leads to Delayed Corneal Wound Healing in Ovariectomized Rats. AB - Hypercalcemia is often observed in postmenopausal women as well as in patients with primary hyperparathyroidism or malignant tumors. In this study, we investigated the relationship between calcium ion (Ca(2+)) levels in lacrimal fluid and the rate of corneal wound healing in hypercalcemia using ovariectomized (OVX) rat debrided corneal epithelium. We also determined the effects of Ca(2+) levels on cell adhesion, proliferation and viability in a human cornea epithelial cell line (HCE-T). The calcium content in bones of OVX rats decreased after ovariectomy. Moreover, the Ca(2+) content in the blood of OVX rats was increased 1 month after ovariectomy, and decreased. The Ca(2+) content in the lacrimal fluid of OVX rats was also increased after ovariectomy, and then decreased similarly as in blood. Corneal wound healing in OVX rats was delayed in comparison with Sham rats (control rats), and a close relationship was observed between the Ca(2+) levels in lacrimal fluid and the rate of corneal wound healing in Sham and OVX rats (y=-0.7863x+8.785, R=0.78, n=25). In addition, an enhancement in Ca(2+) levels caused a decrease in the viability in HCE-T cells. It is possible that enhanced Ca(2+) levels in lacrimal fluid may cause a decrease in the viability of corneal epithelial cells, resulting in a delay in corneal wound healing. These findings provide significant information that can be used to design further studies aimed at reducing corneal damage of patients with hypercalcemia. PMID- 26133717 TI - A Simple Protocol for the Myocardial Differentiation of Human iPS Cells. AB - We have developed a simple protocol for inducing the myocardial differentiation of human induced pluripotent stem (iPS) cells. Human iPS cell-derived embryonic bodies (EBs) were treated with a combination of activin-A, bone morphogenetic protein-4 and wnt-3a for one day in serum-free suspension culture, and were subsequently treated with noggin for three days. Thereafter, the EBs were subjected to adherent culture in media with 5% serum. All EBs were differentiated into spontaneously beating EBs, which were identified by the presence of striated muscles in transmission electron microscopy and the expression of the specific cardiomyocyte markers, NKX2-5 and TNNT2. The beating rate of the beating EBs was decreased by treatment with a rapidly activating delayed rectifier potassium current (Ikr) channel blocker, E-4031, an Ikr trafficking inhibitor, pentamidin, and a slowly activating delayed rectifier potassium current (Iks) channel blocker, chromanol 293B, and was increased by treatment with a beta-receptor agonist, isoproterenol. At a low concentration, verapamil, a calcium channel blocker, increased the beating rate of the beating EBs, while a high concentration decreased this rate. These findings suggest that the spontaneously beating EBs were myocardial cell clusters. This simple protocol for myocardial differentiation would be useful in providing a sufficient number of the beating myocardial cell clusters for studies requiring human myocardium. PMID- 26133718 TI - Deferiprone Protects against Photoreceptor Degeneration Induced by Tunicamycin in the Rat Retina. AB - Endoplasmic reticulum stress has been reported to be involved in the pathogenesis of retinitis pigmentosa, macular degeneration and diabetic retinopathy. In the present study, we examined the effects of deferiprone, an iron chelator, on photoreceptor degeneration induced by tunicamycin (300 nmol/eye), an endoplasmic reticulum stress inducer, in the rat retina. Scotopic electroretinogram measurement and morphometric evaluation were done 7 d after the injection of tunicamycin. In the scotopic electroretinogram, intravitreal deferiprone (5 nmol/eye) injected simultaneously with tunicamycin significantly reduced the decreases in a- and b-wave amplitudes induced by tunicamycin. Morphometric evaluation showed that deferiprone significantly reduced thinning of the outer nuclear layer, the inner segment and the outer segment. These results suggest that iron chelation therapy may be a good candidate for the treatment of eye diseases related to endoplasmic reticulum stress. PMID- 26133719 TI - Fulgidic Acid Isolated from the Rhizomes of Cyperus rotundus Suppresses LPS Induced iNOS, COX-2, TNF-alpha, and IL-6 Expression by AP-1 Inactivation in RAW264.7 Macrophages. AB - To identify bioactive natural products possessing anti-inflammatory activity, the potential of fulgidic acid from the rhizomes of Cyperus rotundus and the underlying mechanisms involved in its anti-inflammatory activity were evaluated in this study. Fulgidic acid reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these findings, fulgidic acid suppressed the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level, as well as iNOS, COX-2, TNF-alpha, and IL-6 at mRNA levels. Fulgidic acid suppressed the LPS-induced transcriptional activity of activator protein-1 (AP-1) as well as the phosphorylation of c-Fos and c-Jun. On the other hand, fulgidic acid did not show any effect on LPS-induced nuclear factor kappaB (NF-kappaB) activity. Taken together, these results suggest that the anti inflammatory effect of fulgidic acid is associated with the suppression of iNOS, COX-2, TNF-alpha, and IL-6 expression through down-regulating AP-1 activation in LPS-induced RAW264.7 macrophages. PMID- 26133720 TI - Excitatory Amino Acid Transporter 1-Mediated L-Glutamate Transport at the Inner Blood-Retinal Barrier: Possible Role in L-Glutamate Elimination from the Retina. AB - The purpose of this study was to elucidate the transport mechanism(s) of L glutamate (L-Glu), a neuroexcitatory neurotransmitter, in the inner blood-retinal barrier (BRB). The L-Glu transport was evaluated by an in vitro uptake study with a conditionally-immortalized rat retinal capillary endothelial cell line, TR iBRB2 cells. L-Glu uptake by TR-iBRB2 exhibited time- and concentration dependence, and was composed of high- and low-affinity processes with Michaelis Menten constants (Km) of 19.3 uM and 275 uM, respectively. Under Na(+)-free conditions, L-Glu uptake by TR-iBRB2 involved one-saturable kinetics with a Km of 190 uM, which is similar to that of the low-affinity process of L-Glu uptake under normal conditions. Moreover, substrates/inhibitors of system Xc(-), which is involved in blood-to-retina transport of compounds across the inner BRB, strongly inhibited the L-Glu uptake under Na(+)-free conditions, suggesting that Na(+)-independent low-affinity L-Glu transport at the inner BRB is carried out by system Xc(-). Regarding the Na(+)-dependent high affinity process of L-Glu transport at the inner BRB, L-Glu uptake by TR-iBRB2 under normal conditions was significantly inhibited by substrates/inhibitors of excitatory amino acid transporter (EAAT) 1-5, but not alanine-serine-cysteine transporters. Reverse transcription polymerase chain reaction (RT-PCR) analysis and immunoblot analysis demonstrated that mRNA and protein of EAAT1 are expressed in TR-iBRB2 cells, whereas mRNAs and/or proteins of EAAT2-5 are not. Immunohistochemical analysis revealed that EAAT1 protein is localized on the abluminal membrane of the retinal capillaries. In conclusion, EAAT1 most likely mediates Na(+)-dependent high affinity L-Glu transport at the inner BRB and appears to take part in L-Glu elimination from the retina across the inner BRB. PMID- 26133721 TI - Isolated trisomy 13 in refractory anemia with excess blasts: report of two cases and a brief literature review of this possible association. PMID- 26133722 TI - Gradual increase of chronic lymphocytic leukemia incidence in Korea, 1999-2010: comparison to plasma cell myeloma. AB - Chronic lymphocytic leukemia (CLL) and plasma cell myeloma (PCM) have markedly higher incidences in Western countries compared with Asian countries. To track the change of incidence in Korea, we investigated the 12-year incidence and compared findings with national cancer databases in Taiwan and the United States (US). The age-standardized incidence rates (ASRs) of CLL and PCM in Korea during 1999-2010 were 0.13/100,000 and 1.23/100,000. The annual percentage change (APC) in the incidence rates were 4.17% for CLL and 4.68% for PCM. These increasing trends were similar findings to Taiwan. In the US, the ASRs of CLL and PCM were 3.21/100 000 and 3.97/100,000. The APC of CLL and PCM incidence rate were 0.68% and 0.50%. The incidence rates of CLL in Korea gradually increased during the study period, while those of PCM showed a steeper ascent. In contrast, the incidence rates of CLL and PCM in the US appear to be stable. PMID- 26133723 TI - Silibinin suppresses NPM-ALK, potently induces apoptosis and enhances chemosensitivity in ALK-positive anaplastic large cell lymphoma. AB - Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), an oncogenic fusion protein carrying constitutively active tyrosine kinase, is known to be central to the pathogenesis of ALK-positive anaplastic large cell lymphoma (ALK+ALCL). Here, it is reported that silibinin, a non-toxic naturally-occurring compound, potently suppressed NPM-ALK and effectively inhibited the growth and soft agar colony formation of ALK+ALCL cells. By western blots, it was found that silibinin efficiently suppressed the phosphorylation/activation of NPM-ALK and its key substrates/downstream mediators (including STAT3, MEK/ERK and Akt) in a time- and dose-dependent manner. Correlating with these observations, silibinin suppressed the expression of Bcl-2, survivin and JunB, all of which are found to be upregulated by NPM-ALK and pathogenetically important in ALK+ALCL. Lastly, silibinin augmented the chemosensitivity of ALK+ALCL cells to doxorubicin, particularly the small cell sub-set expressing the transcriptional activity of Sox2, an embryonic stem cell marker. To conclude, the findings suggest that silibinin might be useful in treating ALK+ALCL. PMID- 26133724 TI - Radioimmunotherapy consolidation using 131I-tositumomab for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma in first remission. AB - Despite initial responses to chemoimmunotherapy, relapse and minimal residual disease (MRD) remain major issues in treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients. We administered (131)I tositumomab to patients in complete response (CR) or partial response (PR) after induction chemotherapy. Toxicities and rate of PR to CR conversion and MRD elimination were assessed three months later. The study stopped prematurely after enrolling 16 patients. Four (25%) were in CR, 12 (75%) in PR, and 12 (75%) had MRD. Three months after treatment with (131)I-tositumomab, CR was achieved (n = 8; 50%) or sustained (n = 4; 25%) in 12 patients and MRD was eliminated in four of 12 patients (33%). Hematologic toxicities were anemia in one patient (6%), neutropenia in 13 (81%), and thrombocytopenia in eight (50%). Two patients (12%) developed MDS 17 and 20 months after consolidation. Consolidation with (131)I tositumomab for CLL/SLL patients in first remission is feasible and may provide the benefit of converting PR to CR and/or eliminating MRD. PMID- 26133725 TI - Circulating miRNA-122, miRNA-199a, and miRNA-16 as Biomarkers for Early Detection of Hepatocellular Carcinoma in Egyptian Patients with Chronic Hepatitis C Virus Infection. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. Having a very poor prognosis, it currently ranks as the third most common cause of cancer-related deaths. MiRNAs are a set of small, single-stranded, non coding RNA molecules that negatively regulate gene expression at the post transcriptional level. Several miRNAs were found to be frequently deregulated in HCC. OBJECTIVE: To investigate whether miRNA-122, miRNA-199a, and miRNA-16 are altered in sera of hepatitis C virus (HCV)-induced HCC patients compared with chronic HCV patients without HCC, and to assess their diagnostic value to differentiate between HCC and chronic HCV in order to develop a non-invasive diagnostic and prognostic tool for HCC. METHODS: We analysed the expression of mature miRNA-122, miRNA-199a, and miRNA-16 in serum by a singleplex TaqMan two step stem loop quantitative real-time reverse-transcription PCR (qRT-PCR) in 40 newly diagnosed HCC patients and 40 chronic HCV liver cirrhosis patients, as well as 20 apparently healthy individuals as a control group, using RNU48 as a normalisation control. RESULTS: Serum miR-16 was significantly lower in HCC than in HCV patients (P = 0.033). The serum level of miR-199a in chronic HCV patients was significantly lower than in healthy controls (P = 0.001). Receiver operating curve (ROC) analysis for serum miRNA-16 for discriminating HCC from HCV patients showed that at the cut-off value of 0.904, the sensitivity and specificity for this marker were 57.5 and 70 %, respectively. The combination of serum miR-16 with serum alpha fetoprotein (AFP) resulted in improved sensitivity to 85% and increased diagnostic accuracy to 87.5 %. Serum miR-199a and miR-16 were significantly associated with several parameters of HCC such as tumour size and number. CONCLUSION: The combination of serum miR-16 and serum AFP is a significant improvement on the current best practice of serum AFP for HCC in HCVpositive patients. Serum miR-199a and miR-16 could be used as potential indicators of the progress of HCC. PMID- 26133726 TI - Acupuncture-induced changes of pressure pain threshold are mediated by segmental inhibition--a randomized controlled trial. AB - Our aim was to distinguish between spinal and supraspinal mechanisms in the intact nervous system by comparing homosegmental and heterosegmental effects of electroacupuncture (EA) and manual acupuncture (MA) on sensory perception in healthy volunteers by means of quantitative sensory testing. Seventy-two healthy volunteers were randomly assigned to receive either MA or EA at SP 6, SP 9, GB 39, and ST 36 at the left leg or relaxed for 30 minutes (control group [CG]). Blinded examiners assessed 13 sensory modalities (thermal and mechanical detection and pain thresholds) at the upper arms and lower legs before and after intervention by means of a standardized quantitative sensory testing battery. Change scores of all 13 sensory thresholds were compared between groups. The main outcome measure was the change score of the pressure pain threshold (PPT). There were no baseline differences between groups. Pressure pain threshold change scores at the lower left leg, in the same segment as the needling site, differed significantly (P = 0.008) between the EA (median: 103.01 kPa) and CG groups (median: 0.00 kPa) but not between the MA (median: 0.00 kPa) and CG groups. No further significant change score differences were found between one of the acupuncture groups and the CG. The PPT can be changed by EA. The PPT increase was confined to the segment of needling, which indicates that it is mainly mediated by segmental inhibition in the spinal cord. This underscores the importance of segmental needling and electrical stimulation in clinical practice. PMID- 26133727 TI - Do psychological factors influence recovery from complex regional pain syndrome type 1? A prospective study. AB - Previous studies have shown that the outcomes of complex regional pain syndrome (CRPS) vary significantly between patients, but few studies have identified prognostic indicators. The aim of this study was to determine whether psychological factors are associated with recovery from recently onset CRPS amongst patients followed prospectively for 1 year. Sixty-six patients with CRPS (type 1) were recruited within 12 weeks of symptom onset and assessed immediately and at 6 and 12 months, during which time they received treatment as usual. At each assessment, the following were measured: signs and symptoms of CRPS, pain, disability, depression, anxiety, stress, pain-related fear, pain catastrophising, laterality task performance, body perception disturbance, and perceived ownership of the limb. Mixed-effects models for repeated measures were conducted to identify baseline variables associated with CRPS severity, pain, and disability over the 12 months. Results showed that scores for all 3 outcome variables improved over the study period. Males and those with lower levels of baseline pain and disability experienced the lowest CRPS severity scores over 12 months. Those with lower baseline anxiety and disability had the lowest pain intensity over the study period, and those with lower baseline pain and pain-related fear experienced the least disability over the 12 months. This suggests that anxiety, pain-related fear, and disability are associated with poorer outcomes in CRPS and could be considered as target variables for early treatment. The findings support the theory that CRPS represents an aberrant protective response to perceived threat of tissue injury. PMID- 26133728 TI - Minimal Modification to the Trerotola Backbleeding Technique Increases Its Effectiveness. AB - Thrombectomy of a clotted upper arm access may be complicated by brachial artery embolization. A number of techniques have been described to relieve the embolization that may not always be successful. Backbleeding is one such technique. We describe a minimal modification that makes backbleeding more effective. PMID- 26133729 TI - Langerhans Cell Histiocytosis (LCH) in Egyptian Children: Does Reactivation Affect the Outcome? AB - OBJECTIVE: To report a single centre outcome of management of Langerhans cell histiocytosis (LCH), a clonal disease with involvement of various body systems. METHODS: Retrospective analysis of 80 pediatric LCH patients at Children Cancer Hospital-Egypt between July 2007 and December 2011 was performed. Patients were stratified and treated according to LCH III protocol. The median follow up period was 42 mo (range: 1.18 to 71 mo). RESULTS: At wk 6 and 12, 'better' response was obtained in 61 (76 %) and 74 (93 %) patients respectively. Afterwards, reactivation occurred in 25 patients (38 %), of them multiple episodes occurred in 5 patients (6.25 %), managed by repetition of 1st line treatment for once or more. The 5 y overall survival (OS) and event free survival (EFS) was 96.3 and 55 % respectively. At last follow up, better status was reached in 70 patients, 3 in each 'intermediate' and 'worse' status. Three high risk patients died and one patient was lost to follow up. CONCLUSIONS: In a single Egyptian pediatric LCH experience, the response to treatment is satisfactory and survival remains the rule except in high risk organs disease that still needs a new molecule for salvage. However in multiple reactivations, patients do well with repetition of the 1st line of treatment with or without methotrexate. PMID- 26133730 TI - Risk Factors for Steroid Dependency in Children with Idiopathic Nephrotic Syndrome in India. PMID- 26133731 TI - Rare Association of Chiari's Network and Ventricular Arrhythmias in a Late Premature Neonate. PMID- 26133732 TI - Genetic dissection on rice grain shape by the two-dimensional image analysis in one japonica * indica population consisting of recombinant inbred lines. AB - KEY MESSAGE: This article used seven characters from the 2D image analysis to dissect the genetic architecture underlying rice grain shape in one japonica * indica population consisting of 215 recombinant inbred lines. Two-dimensional (2D) digital image analysis is efficient for investigating the rice grain shape characters in large genetic and breeding populations. In this study, we used 2D image analysis to investigate seven characters, i.e., grain length (GL), grain width (GW), length-to-width ratio (LW), grain area (GA), grain circumference (GC), grain diameter (GD), and grain roundness (GR), in one japonica * indica genetic population consisting of 215 recombinant inbred lines. GL and GW can be recorded manually as well, and have been extensively used together with LW (i.e., GL/GW) in genetic studies on grain shape. GC and GA can be hardly measured manually, and have not been used together with GD and GR. Results indicated that the seven characters could be precisely measured by 2D image analysis, genotype by environment interaction was low, and heritability was high. Each character was controlled by a few major stable genes and multiple minor additive genes. A total of 51 QTL were detected for the seven characters across four diverse environments, 22 from GL, GW, and LW, the three traditional characters, and 29 from the other four characters. The 51 QTL were clustered in eighteen marker intervals. Comparing with previous studies and analyzing the stability of identified QTL, we found six non-reported marker intervals, one each on chromosomes 2 and 3, and two each on chromosomes 6 and 8. The newly identified loci and the large-scale phenotyping system would greatly improve our knowledge about the genetic architecture and the future rice breeding on grain shape. PMID- 26133733 TI - Genome-wide association analysis of symbiotic nitrogen fixation in common bean. AB - KEY MESSAGE: Significant SNPs and candidate genes for symbiotic nitrogen fixation (SNF) and related traits were identified on Pv03, Pv07 and Pv09 chromosomes of common bean. A genome-wide association study (GWAS) was conducted to explore the genetic basis of variation for symbiotic nitrogen fixation (SNF) and related traits in the Andean Diversity Panel (ADP) comprising 259 common bean (Phaseolus vulgaris) genotypes. The ADP was evaluated for SNF and related traits in both greenhouse and field experiments. After accounting for population structure and cryptic relatedness, significant SNPs were identified on chromosomes Pv03, Pv07 and Pv09 for nitrogen derived from atmosphere (Ndfa) in the shoot at flowering, and for Ndfa in seed. The SNPs for Ndfa in shoot and Ndfa in seed co-localized on Pv03 and Pv09. Two genes Phvul.007G050500 and Phvul.009G136200 that code for leucine-rich repeat receptor-like protein kinases (LRR-RLK) were identified as candidate genes for Ndfa. LRR-RLK genes play a key role in signal transduction required for nodule formation. Significant SNPs identified in this study could potentially be used in marker-assisted breeding to accelerate genetic improvement of common bean for SNF. PMID- 26133734 TI - Mapping quantitative trait loci for peroxidase activity and developing gene specific markers for TaPod-A1 on wheat chromosome 3AL. AB - KEY MESSAGE: Three novel QTL for peroxidase activity were mapped, and gene specific markers for TaPod-A1 were developed and validated using RILs derived from the Doumai/Shi 4185 cross and 281 wheat cultivars. TaPod-A1 is within one of the three QTL. Peroxidase (POD) activity in grain is an important factor determining the color of flour and end-use products of wheat, such as noodles and steamed bread. Mapping QTL for POD activity, characterization of POD genes and development of gene-specific markers are important for molecular marker-assisted selection in wheat breeding. Quantitative trait loci (QTL) for POD activity in common wheat were mapped using a recombinant inbred line (RIL) population derived from a Doumai/Shi 4185 cross grown in four environments and genotyped using the wheat 90 K iSelect assay. Three novel QTL for POD activity, QPod.caas-3AL, QPod.caas-4BS and QPod.caas-5AS, were identified on chromosomes 3AL, 4BS and 5AS, explaining 5.3-21.2% of phenotypic variance across environments. The full-length genomic DNA (gDNA) sequence of a POD gene, designated TaPod-A1, on chromosome 3A was characterized by homolog cloning and PCR verification. Two complementary dominant sequence-tagged site (STS) markers, POD-3A1 and POD-3A2, were developed based on single nucleotide polymorphisms (SNPs) between two alleles at the TaPod A1 locus, amplifying 291- and 766-bp fragments in cultivars with lower and higher POD activities, respectively. The two gene-specific markers were mapped on chromosome 3AL using a set of Chinese Spring (CS) nulli-tetrasomic lines, and ditelosomic lines 3AL and 3AS. QTL analysis indicated that QPod.caas-3AL co segregated with the gene-specific markers POD-3A1 and POD-3A2. POD-3A1 and POD 3A2 were verified on 281 wheat cultivars and advanced lines, and showed significant (P < 0.05) associations with POD activities. POD-3A1 and POD-3A2 may be useful as markers for improving color attributes in wheat breeding programs. PMID- 26133735 TI - Molecular tagging of a new broad-spectrum powdery mildew resistance allele Pm2c in Chinese wheat landrace Niaomai. AB - KEY MESSAGE: A new broad-spectrum powdery mildew resistance allele Pm2c was identified and mapped in Chinese wheat landrace Niaomai. Chinese wheat landrace Niaomai showed resistance to 27 of 28 Chinese Blumeria graminis f. sp tritici (Bgt) races. Genetic analysis of an F2 population and its derived F2:3 families from the cross Niaomai * Mingxian 169 and backcross population, Niaomai/2*Mingxian 169, indicated that the resistance of Niaomai to Bgt races was conferred by a single dominant resistance gene, temporarily designated PmNM. Molecular tagging showed that PmNM was located on chromosome 5DS and flanked by SSR markers Xcfd81 and Xcfd78 with the genetic distances of 0.1/0.4 cM and 4.9/7.5 cM, respectively. Niaomai showed a different array of responses compared to lines with Pm2a, Pm2b, PmD57-5D, PmLX66, PmX3986-2 and Pm48 genes, sharing the same Xcfd81 allele but differing from Xcfd78 allele for Pm2a and Pm2b lines. Allelism tests based on crosses of Niaomai with Ulka/8*Cc and KM2939 showed that PmNM is allelic to Pm2a and Pm2b. We concluded that PmNM is a new allele of Pm2, re-designated Pm2c. Pm2c could be transferred into wheat cultivars by marker assisted selection to improve the powdery mildew resistance of breeding cultivars/lines. PMID- 26133736 TI - Anxiogenic role of vasopressin during the early postnatal period: maternal separation-induced ultrasound vocalization in vasopressin-deficient Brattleboro rats. AB - Both animal and human studies suggest that in adulthood, plasma vasopressin level correlates well with anxiety. Little is known about the mood regulation during the perinatal period. Here, we aim to investigate the influence of vasopressin on anxiety during the early postnatal age. As a sign of distress, rat pups emit ultrasonic vocalizations (USVs) when they are separated from their mother. This USV was detected in 7- to 8-day-old vasopressin-deficient Brattleboro pups, and they were compared to their heterozygote littermates and wild-type pups. The results were confirmed by V1b antagonist treatment (SSR149415 10 mg/kg ip 30 min before test) in wild-types. Chlordiazepoxide (3 mg/kg ip 30 min before test)-an anxiolytic-was used to test the interaction with the GABAergic system. At the end of the test, stress-hormone levels were measured by radioimmunoassay. Vasopressin deficient pups vocalized substantially less than non-deficient counterparts. Treatment with V1b antagonist resulted in similar effect. Chlordiazepoxide reduced the frequency and duration of the vocalization only in wild-types. Reduced vocalization was accompanied by smaller adrenocorticotropin levels but the level of corticosterone was variable. Our results indicate that the anxiolytic effect of vasopressin deficiency (both genetic and pharmacological) exists already during the early postnatal age. Vasopressin interacts with the GABAergic system. As mood regulation does not go parallel with glucocorticoid levels, we suggest that vasopressin might have a direct effect on special brain areas. PMID- 26133737 TI - Taurine supplementation preserves hypothalamic leptin action in normal and protein-restricted mice fed on a high-fat diet. AB - Malnutrition programs the neuroendocrine axis by disruption of food-intake control, leading to obesity. Taurine (Tau) is neuroprotective and improves anorexigenic actions in the hypothalamus. We evaluated the hypothalamic gene expression profile and food-intake control in protein-restricted mice submitted to a high-fat diet (HFD) and Tau supplementation. Mice were fed on a control (14 % protein-C) or a protein-restricted diet (6 % protein-R) for 6 weeks. Thereafter, mice received, or not, HFD for 8 weeks (CH and RH) with or without 5 % Tau supplementation (CHT and RHT). Protein restriction led to higher food intake, but calories were matched to controls. Excessive calorie intake occurred in HFD mice and this was prevented by Tau supplementation only in the CH group. Additionally, RH and CH mice developed hypothalamic leptin resistance, which was prevented by Tau. Global alterations in the expressions of genes involved in hypothalamic metabolism, cellular defense, apoptosis and endoplasmic reticulum stress pathways were induced by dietary manipulations and Tau treatment. The orexigenic peptides NPY and AgRP were increased by protein restriction and lowered by the HFD. The anorexigenic peptide Pomc was increased by HFD, and this was prevented by Tau only in CH mice. Thus, food intake was disrupted by dietary protein restriction and obesity. HFD-induced alterations were not enhanced by previous protein deficiency, but the some beneficial effects of Tau supplementation upon food intake were blunted by protein restriction. Tau effects upon feeding behavior control are complex and involve interactions with a vast gene network, preventing hypothalamic leptin resistance. PMID- 26133738 TI - Transglutaminase 2 up-regulation is associated with RANKL/OPG pathway in cultured HPDL cells and THP-1-differentiated macrophages. AB - Recent evidence emphasized that transglutaminase 2 (TG2), a protein cross-linking enzyme, may play a role in the early phase of inflammation. High levels of TG2 have been associated with the constitutive activation of nuclear factor-kappa B (NF-kappaB) that is considered the main regulator of inflammation. In this context, the receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-kappaB have extensive functions in the regulation of cytokine secretion associated with different pathological conditions. The human periodontal ligament (HPDL) cells, which express and secrete osteoprotegerin (OPG) and RANKL, represent an useful "ex vivo" model for monitoring cell response in inflammatory microenvironments, such as periodontitis-dependent tissue response. Thus, we evaluated TG2 expression and alterations in RANKL/OPG ratio occurring in cultured HPDL cells. The HPDL cells were obtained from patients with chronic periodontitis (CP) and healthy subjects. We observed the up-regulation of some inflammatory markers, such as IL-6, TNF-alpha, and HMGB-1, and at the same time an increase in TG2 mRNA levels in HPDL cells from CP patients compared with healthy subjects. We found a positive correlation between RANKL/OPG ratio and TG2 mRNA levels in HPDL cells from CP patients. In the parallel experiments, we demonstrated that TG2 inhibition reduced RANKL expression in both HPDL cells from CP patients and monocytes differentiated to macrophages by tetradecanoyl phorbol acetate treatment. Given the RANKL key role in NF-kappaB pathway and the observed up-regulation of pro-inflammatory cytokines, our data suggest that TG2 may be involved in molecular mechanisms of inflammatory response occurring in periodontal disease. PMID- 26133739 TI - The Space From Heart Disease Intervention for People With Cardiovascular Disease and Distress: A Mixed-Methods Study. AB - BACKGROUND: Poor self-management of symptoms and psychological distress leads to worse outcomes and excess health service use in cardiovascular disease (CVD). Online-delivered therapy is effective, but generic interventions lack relevance for people with specific long-term conditions, such as cardiovascular disease. OBJECTIVE: To develop a comprehensive online CVD-specific intervention to improve both self-management and well-being, and to test acceptability and feasibility. METHODS: Informed by the Medical Research Council (MRC) guidance for the development of complex interventions, we adapted an existing evidence-based generic intervention for depression and anxiety for people with CVD. Content was informed by a literature review of existing resources and trial evidence, and the findings of a focus group study. Think-aloud usability testing was conducted to identify improvements to design and content. Acceptability and feasibility were tested in a cross-sectional study. RESULTS: Focus group participants (n=10) agreed that no existing resource met all their needs. Improvements such as "collapse and expand" features were added based on findings that participants' information needs varied, and specific information, such as detecting heart attacks and when to seek help, was added. Think-aloud testing (n=2) led to changes in font size and design changes around navigation. All participants of the cross-sectional study (10/10, 100%) were able to access and use the intervention. Reported satisfaction was good, although the intervention was perceived to lack relevance for people without comorbid psychological distress. CONCLUSIONS: We have developed an evidence-based, theory-informed, user-led online intervention for improving self-management and well-being in CVD. The use of multiple evaluation tests informed improvements to content and usability. Preliminary acceptability and feasibility has been demonstrated. The Space from Heart Disease intervention is now ready to be tested for effectiveness. This work has also identified that people with CVD symptoms and comorbid distress would be the most appropriate sample for a future randomized controlled trial to evaluate its effectiveness. PMID- 26133740 TI - Renal cortical necrosis is a disappearing entity in obstetric acute kidney injury in developing countries: our three decade of experience from India. AB - RATIONAL: Obstetrical complications are the commonest causes of Renal Cortical Necrosis (RCN). However, the overall incidence of RCN in obstetric acute kidney injury in developing countries has been decreasing in recent years. OBJECTIVE: The aim of this study was to evaluate the changing profile of RCN in obstetric AKI over the last three decades. METHODS: This single center study included patients with biopsy proven renal cortical necrosis over a period of 32 years from 1982 to 2014. The diagnosis of RCN was suspected in patients with prolonged AKI (>4 weeks) with absolute anuria in the setting of hemorrhage, hypotension and sepsis; and was confirmed by renal biopsy. The changing pattern in the incidence, etiology and outcome of RCN in patients with obstetric AKI was compared in the three study periods, namely 1982-1991, 1992-2002 and 2003-2014. RESULTS: Over a period of 32 years, RCN was diagnosed in 15/259(5.8%) cases of obstetric AKI. Diffuse and patchy cortical necrosis were noted in 8(53.3%) and 7(46.7%) patients, respectively. RCN occurred in 17%(11/65), 2.4%(3/125) and 1.44%(1/69) patients in 1982-1991, 1992-2002 and 2003-2014, respectively. Septic abortion was commonest cause of RCN in the first two study periods but no case was observed in last decade. The decrease in incidence of RCN over the three decades was statistically significant (p-value < 0.001). Maternal mortality decreased to zero in 2003-2014 from 72.7% in 1982-1991. CONCLUSIONS: The incidence of RCN in obstetric AKI in developing countries has declined low enough to label it as a disappearing entity. PMID- 26133741 TI - Heparin calcium treated Henoch-Schonlein purpura nephritis in children through inhibiting hyperfibrinolysis. AB - AIM: To explore the underlying mechanism of low-molecular-weight heparin calcium therapy on Henoch-Schonlein purpura nephritis (HSPN). METHODS: Eighty-nine children with severe HSPN were randomized into control group (treated with conventional therapy, n = 45) and treatment group (treated with conventional therapy plus low-molecular-weight heparin calcium, n = 44). The concentrations of plasma fibrinogen (Fg), d-dimer and fibrin degradation products (FDPs) were detected before and after treatment. The urinary red blood cell (RBC) and 24 h proteinuria were determined weekly for assessing the children's kidney function. RESULTS: Two groups were well-matched at baseline. After 8 weeks of treatment, the clinical outcomes of HSPN and outcome of proteinuria of the treatment group were better than the control group (p < 0.05); the content of Fg, d-dimer and FDP in plasma of the treatment group were lower than the control group (p < 0.05); but there was no difference about the curative effect of hematuria and the coagulation function between the two groups (p > 0.05). CONCLUSIONS: Fibrinolytic system may participate in the kidney injury of HSPN children and low-molecular weight heparin calcium could correct blood hypercoagulability through inhibiting hyperfibrinolysis, and thus improving the blood supply of kidney. PMID- 26133742 TI - Placental growth factor and placental protein 13 in patients with Balkan endemic nephropathy, a worldwide disease. AB - BACKGROUND: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease occurring in people living in along the tributaries of the Danube River. The aim of the study was to determine serum level and urinary excretion of placental growth factor (PlGF) and placental protein 13 (PP13) in patients with BEN. METHODS: Thirty patients with BEN from the South Morava River region of Serbia and 18 controls were studied. Age of patients was 74 yr (53-87) and 73 yr (66-83) in controls. RESULTS: In patients with BEN, serum creatinine was significantly higher than in controls (129.7 vs. 83.2 umol/L, respectively), but GFR was lower in patients than in controls (40.7 vs. 54.6 mL/min). Serum PlGF was significantly higher in BEN patients than in controls (9.90 vs. 6.80 pg/mL), urinary excretion being significantly lower in patients (0.20 vs. 0.90 pg/mmol creat.). Serum PP13 was significantly lower in BEN patients (208.2 vs. 291.0 pg/mL). Urinary excretion of PP13 was also significantly lower in BEN patients than in controls (32.5 vs. 182.5 pg/mmol creat). In multivariate regression analysis BEN, sex and age were significant determinants of the observed changes in PlGF and PP13. CONCLUSION: Important changes of PlGF and PP13 in patients with BEN were demonstrated, where kidney disease, female sex, and the age have been significant determinants. PMID- 26133743 TI - Gender Role, Gender Identity and Sexual Orientation in CAIS ("XY-Women") Compared With Subfertile and Infertile 46,XX Women. AB - The perception of gender development of individuals with complete androgen insensitivity syndrome (CAIS) as unambiguously female has recently been challenged in both qualitative data and case reports of male gender identity. The aim of the mixed-method study presented was to examine the self-perception of CAIS individuals regarding different aspects of gender and to identify commonalities and differences in comparison with subfertile and infertile XX chromosomal women with diagnoses of Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) and polycystic ovary syndrome (PCOS). The study sample comprised 11 participants with CAIS, 49 with MRKHS, and 55 with PCOS. Gender identity was assessed by means of a multidimensional instrument, which showed significant differences between the CAIS group and the XX-chromosomal women. Other-than female gender roles and neither-female-nor-male sexes/genders were reported only by individuals with CAIS. The percentage with a not exclusively androphile sexual orientation was unexceptionally high in the CAIS group compared to the prevalence in "normative" women and the clinical groups. The findings support the assumption made by Meyer-Bahlburg ( 2010 ) that gender outcome in people with CAIS is more variable than generally stated. Parents and professionals should thus be open to courses of gender development other than typically female in individuals with CAIS. PMID- 26133744 TI - Visible to near-infrared plasmon-enhanced catalytic activity of Pd hexagonal nanoplates for the Suzuki coupling reaction. AB - Photocatalytic conversion of solar energy to chemical energy is an efficient process in green chemistry because it facilitates room temperature chemical transformations by generating electronically excited states in photocatalysts. We report here on the robust synthesis, detailed structural characterization, and especially photocatalytic properties of plasmonic Pd hexagonal nanoplates for chemical reactions. The Pd hexagonal nanoplates are twin crystals, and composed of the top and bottom faces enclosed by the {111} planes with stacking faults and the side surfaces bound by mixed six {111} and six {100} planes. The Pd hexagonal nanoplates with well-defined and tunable longitudinal localized surface plasmon resonance (LSPR) have enabled the direct harvesting of visible to near-infrared light for catalytic cross coupling reactions. Upon plasmon excitation, the catalytic Suzuki coupling reactions of iodobenzene and phenylboronic acid accelerate by a plasmonic photocatalytic effect of plasmon induced hot electrons. The turnover frequency (TOF) of the Pd hexagonal nanoplates in a reaction illuminated with a lambda = 300-1000 nm Xenon lamp at 176 mW cm(-2) was 2.5 and 2.7 times higher than that of non-plasmonic {111}-enclosed Pd nanooctahedra and {100}-enclosed Pd nanocubes, respectively, and 1.7 times higher than the TOF obtained when the reaction was thermally heated to the same temperature. PMID- 26133746 TI - Comments on 'Sample size calculation for the proportional hazards cure model' by Songfeng Wang, Jiajia Zhang and Wenbin Lu. PMID- 26133747 TI - Authors' reply to comments on 'Sample size calculation for the proportional hazards cure model'. PMID- 26133745 TI - Phone behaviour and its relationship to loneliness in older adults. AB - OBJECTIVES: Loneliness and social isolation are two important health outcomes among older adults. Current assessment of these outcomes relies on self-report which is susceptible to bias. This paper reports on the relationship between loneliness and objective measures of isolation using a phone monitoring device. METHOD: Phone monitors were installed in the homes of 26 independent elderly individuals from the ORCATECH Life Laboratory cohort (age 86 +/- 4.5, 88% female) and used to monitor the daily phone usage for an average of 174 days. Loneliness was assessed using the 20-item University of California Los Angeles (UCLA) Loneliness scale. A mixed effects negative binomial regression was used to model the relationship between loneliness and social isolation, as assessed using the total number of calls, controlling for cognitive function, pain, age, gender, and weekday. A secondary analysis examined the differential effect of loneliness on incoming and outgoing calls. RESULTS: The average UCLA Loneliness score was 35.3 +/- 7.6, and the median daily number of calls was 4. Loneliness was negatively associated with telephone use (IRR = 0.99, p < 0.05). Daily phone use was also associated with gender (IRR = 2.03, p < 0.001) and cognitive status (IRR = 1.51, p < 0.001). The secondary analysis revealed that loneliness was significantly related to incoming (IRR = 0.98, p < 0.01) but not outgoing calls. CONCLUSIONS: These results demonstrate the close relationship between loneliness and social isolation, showing that phone behaviour is associated with emotional state and cognitive function. Because phone behaviour can be monitored unobtrusively, it may be possible to sense loneliness levels in older adults using objective assessments of key aspects of behaviour. PMID- 26133748 TI - The subparaneurial compartment: A new concept in the clinicoanatomic classification of peripheral nerve lesions. AB - Based on our experience in treating peripheral non-neural sheath derived pathology, we have identified a novel pattern of lesion progression along the anatomic course of nerves. This report highlights the existence of a subparaneurial compartment around peripheral nerves. We first applied an anatomic framework to review MR images and intraoperative photographs of patients treated by the senior author in the last 10 years. After identifying a pattern that was consistent with subparaneurial lesion progression, we searched for other examples of cases that might exhibit this pattern. Four examples of subparaneurial pathology were identified, a hemangioma of the ulnar nerve, a ganglion cyst of the common fibular nerve, a lymphoma of the sciatic nerve and a lipoma of the ulnar nerve. All four patients were operated on and had intraoperative photographs; three had high resolution MR imaging. This report highlights the existence of pathology contained within a subparaneurial compartment, outside of the epineurium, that follows the course of the nerve and surrounds it circumferentially. The subparaneurial localization of peripheral nerve lesions has hitherto received little attention. Identification of this new pattern on preoperative MRI may have implications for surgical management. PMID- 26133749 TI - Prevalence and prognostic value of hepatic histological alterations in patients with Crohn's disease. AB - Variable degrees of liver histological changes in patients with Crohn's disease (CD) have been reported. OBJECTIVE: To evaluate the liver histological alterations and their prognostic significance in patients affected by CD without abnormalities of liver biochemical parameters and ultrasound features. MATERIAL AND METHODS: A prospective, single-blind study, including 35 consecutive patients with CD that underwent bowel resection with a contemporary performance of liver biopsy from 1992 to 2003. EXCLUSION CRITERIA: the presence of standard causes of liver disease, such as alcohol consumption exceeding 20 g/day, primary sclerosing cholangitis, viral infections, celiac disease, metabolic syndrome and alterations of the metabolism. Patients were followed up with regular evaluation of hepatic cytolysis, cholestasis, synthesis and ultrasound performance. After a mean interval of 14 years (from May to December 2013), liver fibrosis was assessed by Fibroscan(r). RESULTS: Histological alterations were shown in 60% of patients, without serious liver injuries (no case of inflammation or significant fibrosis). Fibroscan(r) was performed in 33 subjects and no significant changes were observed (mean value of liver stiffness: 5.2 +/- 1.2 kPa). The minimal microscopic damage did not evolve either in patients with a normal histology or in those with an altered histology at baseline (p = 0.9). Only patients who took azathioprine had a statistically significant increase of liver stiffness values (5.7 +/- 1.5 kPa vs 4.7 +/- 1.3 kPa, p = 0.017). CONCLUSIONS: Patients with CD do not need additional examinations compared to the general population, unless clinical or biochemical abnormalities are found. PMID- 26133751 TI - Anti-Obesity Effects of the Mixture of Eriobotrya japonica and Nelumbo nucifera in Adipocytes and High-Fat Diet-Induced Obese Mice. AB - The present study is to evaluate the anti-obesity effects of Eriobotrya japonica (EJ), Nelumbo nucifera (NN), and their mixture (MIX, 1:1 ratio) in 3T3-L1 adipocytes and high-fat diet-induced obese mice. The treatment of EJ, NN, and MIX in 3T3-L1 adipocytes effectively inhibited lipid accumulation, significantly decreased expression of peroxisome proliferator-activated receptor gamma (PPARgamma), sterol regulatory element binding protein (SREBP1c), and adipocyte lipid-binding protein (aP2), and significantly increased phosphorylation of AMP activated protein kinase (AMPK). Moreover, oral treatment of MIX showed stronger effects than individual treatment. C57BL/6J mice (6 week old) were divided into two groups; low fat diet (LFD) containing 10% calories from fat and high fat diet (HFD) containing 60% calories from fat. The HFD groups were further divided into five subgroups; treated with distilled water (HFD), treated with 400 mg/kg EJ (EJ400), treated with 400 mg/kg NN (NN400), treated with 200 mg/kg MIX (MIX200), and treated with 400 mg/kg MIX (MIX400) during 13 weeks. In our results, the administration of EJ, NN, and MIX significantly decreased body weight (BW), fat weight, liver weight, hepatic triglyceride (TG) and total cholesterol (TC), lipid droplets in the liver, food efficacy ratio, and the plasma TG, TC, glucose, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in a dose-dependent manner, and MIX treatment showed stronger effect than their individual treatments. Similarly, MIX treatment decreased the expression of PPARgamma, SREBP-1c, FAS, and ACC more strongly in the adipose tissue than single treatments. In conclusion, the MIX of EJ and NN extract may strongly regulate BW gain than EJ or NN alone, and its anti-obesity effect is associated with the control of lipid metabolism, including adipogenesis and lipogenesis. PMID- 26133750 TI - Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium tuberculosis Infection in HIV-Infected Individuals. AB - Cytokines are signaling biomolecules that serve as key regulators of our immune system. CD4(+) T-cells can be grouped into 2 major categories based on their cytokine profile: T-helper 1 (TH1) subset and T-helper 2 (TH2) subset. Protective immunity against HIV infection requires TH1-directed CD4 T-cell responses, mediated by cytokines, such as interleukin-1beta (IL-1beta), IL-12, interferon gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). Cytokines released by the TH1 subset of CD4 T-cells are considered important for mediating effective immune responses against intracellular pathogens such as Mycobacterium tuberculosis (M. tb). Oxidative stress and redox imbalance that occur during HIV infection often lead to inappropriate immune responses. Glutathione (GSH) is an antioxidant present in nearly all cells and is recognized for its function in maintaining redox homeostasis. Our laboratory previously reported that individuals with HIV infection have lower levels of GSH. In this study, we report a link between lower levels of GSH and dysregulation of TH1- and TH2-associated cytokines in the plasma samples of HIV-positive subjects. Furthermore, we demonstrate that supplementing individuals with HIV infection for 13 weeks with liposomal GSH (lGSH) resulted in a significant increase in the levels of TH1 cytokines, IL-1beta, IL-12, IFN-gamma, and TNF-alpha. lGSH supplementation in individuals with HIV infection also resulted in a substantial decrease in the levels of free radicals and immunosuppressive cytokines, IL-10 and TGF-beta, relative to those in a placebo-controlled cohort. Finally, we determined the effects of lGSH supplementation in improving the functions of immune cells to control M. tb infection by conducting in vitro assays using peripheral blood mononuclear cells collected from HIV-positive individuals at post-GSH supplementation. Our studies establish a correlation between low levels of GSH and increased susceptibility to M. tb infection through TH2-directed response, which may be relieved with lGSH supplementation enhancing the TH1 response. PMID- 26133752 TI - UPLC/Q-TOFMS-Based Metabolomics Studies on the Protective Effect of Panax notoginseng Saponins on Alcoholic Liver Injury. AB - Consistent, excessive alcohol consumption leads to liver injury. The aim of the present study is to evaluate the possible efficacy of Panax notoginseng saponins (PNS) against chronic alcohol-induced liver injury using LC-MS-based urinary metabolomics. Mice were fed a Lieber-DeCarli liquid diet containing alcohol or isocaloric maltose dextrin as a control diet with or without PNS (200 mg/kg/BW) for 4 weeks. Treatment with PNS significantly reduced the increases in plasma ALT and AST levels, hepatic levels of reactive oxygen species (ROS) and malondialdehyde (MDA), which induced by chronic alcohol exposure. Conversely, PNS was also found to restore the glutathione (GSH) depletion and increase the superoxide dismutase (SOD) activities. The end-point urine sample of each mouse was collected overnight (24 h) in metabolic cages and their metabolic profiling changes were analyzed using UPLC/Q-TOFMS followed by multivariate statistical analysis. After 4 week of Lieber-DeCarli alcohol diet feeding, the metabolic profile experienced great perturbation in PCA score plot, and the treatment of PNS could assist to regulate the disturbed metabolic profile induced by alcohol exposure. Additionally, sixteen potential biomarkers responsible for derivations of the metabolic profile induced by alcohol exposure were identified, and the alcohol-induced changes in these biomarkers, except hexanoylglycine, could be partially or nearly reversed by PNS treatment. Taken together, PNS protects against chronic alcohol-induced liver injury. Our findings demonstrated that the LC-MS-based metabolomics approach is a useful tool to investigate the efficacy of Chinese medicines. PMID- 26133753 TI - BMP-2 Derived Peptide and Dexamethasone Incorporated Mesoporous Silica Nanoparticles for Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells. AB - Bone morphogenetic protein-2 (BMP-2), a growth factor that induces osteoblast differentiation and promotes bone regeneration, has been extensively investigated in bone tissue engineering. The peptides of bioactive domains, corresponding to residues 73-92 of BMP-2 become an alternative to reduce adverse side effects caused by the use of high doses of BMP-2 protein. In this study, BMP-2 peptide functionalized mesoporous silica nanoparticles (MSNs-pep) were synthesized by covalently grafting BMP-2 peptide on the surface of nanoparticles via an aminosilane linker, and dexamethasone (DEX) was then loaded into the channel of MSNs to construct nanoparticulate osteogenic delivery systems (DEX@MSNs-pep). The in vitro cell viability of MSNs-pep was tested with bone mesenchymal stem cells (BMSCs) exposure to different particle concentrations, revealing that the functionalized MSNs had better cytocompatibility than their bare counterparts, and the cellular uptake efficiency of MSNs-pep was remarkably larger than that of bare MSNs. The in vitro results also show that the MSNs-pep promoted osteogenic differentiation of BMSCs in terms of the levels of alkaline phosphatase (ALP) activity, calcium deposition, and expression of bone-related protein. Moreover, the osteogenic differentiation of BMSCs can be further enhanced by incorporating of DEX into MSNs-pep. After intramuscular implantation in rats for 3 weeks, the computed tomography (CT) images and histological examination indicate that this nanoparticulate osteogenic delivery system induces effective osteoblast differentiation and bone regeneration in vivo. Collectively, the BMP-2 peptide and DEX incorporated MSNs can act synergistically to enhance osteogenic differentiation of BMSCs, which have potential applications in bone tissue engineering. PMID- 26133754 TI - Preparation and Supramolecular Recognition of Multivalent Peptide-Polysaccharide Conjugates by Cucurbit[8]uril in Hydrogel Formation. AB - Supramolecular hydrogels were fabricated by physically cross-linking phenylalanine functionalized polysaccharides with cucurbit[8]uril in water. We report a facile 2-step method of functionalization of the polysaccharides hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), and guar with the dipeptide Phe-Cys. Addition of cucurbit[8]uril to the functional polysaccharides initiated physical cross-linking on account of strong 1:2 "homoternary" complexes with the pendant Phe residues. In particular, HA and CMC based soft hydrogels displayed impressive viscoelastic behavior which was characterized using rheology, demonstrating accessibility to an array of material properties which would find broad applicability in many fields. PMID- 26133755 TI - Cushing's syndrome: an update on current pharmacotherapy and future directions. AB - INTRODUCTION: Endogenous Cushing's syndrome (CS) is characterized by chronic overproduction of cortisol and is associated with increased mortality and morbidity. It can be caused by a pituitary adenoma, ectopic adrenocorticotropic hormone (ACTH) production or primary adrenal disease. Successful tumor-directed surgery is the keystone treatment. When surgery is unsuccessful, contraindicated or in case of acute disease, pharmacotherapy is indicated to treat hypercortisolism. AREAS COVERED: In this review, pharmacotherapeutic options for CS will be covered discussing the different possible targets, that is: i) inhibition of ACTH secretion; ii) suppression of steroidogenesis; and iii) blockade of cortisol effects at tissue level. Preclinical and clinical studies will be discussed considering mono- and combination therapy, taking into account efficacy, toxicity and mechanism of action. Per CS entity, future directions of pharmacotherapies will be addressed. EXPERT OPINION: The number of medical treatment options for CS has increased in the past years. In contrast to decades ago, prospective trials are now being performed focusing on pituitary-directed drugs like pasireotide, the glucocorticoid receptor blocker mifepristone and 'new generation' steroid synthesis inhibitors. Future studies will focus on tumor shrinking effects of neuromodulatory drugs, the optimal order and combination of pharmacotherapy, long-term efficacy and safety and new targets for medical treatment of CS. PMID- 26133756 TI - Visual Prognosis and Ocular Complications in Herpetic versus HLA-B27- or Ankylosing Spondylitis-associated Anterior Uveitis. AB - PURPOSE: To investigate the visual prognosis and ocular complications in patients with herpetic versus HLA-B27 associated anterior uveitis (AU). METHODS: This was a retrospective, observational study conducted at the ophthalmology department of the University Medical Center of Groningen. Sixty-two herpetic and 113 HLA-B27 associated AU patients were included. The main outcome measures were visual acuity and ocular complications. RESULTS: Visual acuity over time was significantly lower in herpetic as compared to HLA-B27 AU, mainly due to corneal scarring. The incidence rate of any ocular complication was higher in herpetic AU compared to HLA-B27-associated AU (0.140/EY versus 0.076/EY, p = <0.001), which was mainly due to glaucoma (0.033/EY versus 0.004/EY, p < 0.001) and cataract (0.059/EY versus 0.023/EY, p < 0.001). CONCLUSIONS: The most prominent finding was a worse visual prognosis in herpetic AU, which is probably related to higher prevalence of corneal scarring and glaucoma. In addition, herpetic AU patients have more ocular complications overall. PMID- 26133758 TI - Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats. AB - Shenfu decoction (SFD) can be used to treat patients with sign of Yangqi decline or Yang exhaustion related to chronic heart failure (CHF). We conducted a gas chromatography with time-of-flight mass spectrometer (GC/TOF-MS)-based metabolomic study to increase the understanding of CHF and assess the efficacies and mechanisms of SFD in treating CHF induced by coronary artery ligation in rats. Based on unsupervised principal component analysis, there was a clear separation between the CHF and sham surgery group, which revealed that CHF disturbed the metabolism of endogenous substances and significantly altered the urine metabolite fingerprints. After SFD treatment, the metabolomics profile found in CHF was significantly reversed, shifting much closer to normal controls and sham surgery group, indicating that SFD has therapeutic effects in CHF, which is in accordance with the hemodynamic assay results. Metabolomic pathway analysis demonstrated that several pathways including fatty acid biosynthesis, fatty acid elongation, steroid biosynthesis, galactose metabolism, and amino acid metabolism were significantly altered in CHF rats. Therefore, we may infer that SFD shows therapeutic efficacy in CHF by restoring these disturbed metabolic pathways, especially those related to energy metabolism. This study offers new methodologies for increasing the understanding of CHF and systematically characterizing the efficacies and mechanisms of SFD in treating CHF. PMID- 26133757 TI - The role and potential of umbilical cord blood in an era of new therapies: a review. AB - In light of pioneering findings in the 1980s and an estimation of more than 130 million global annual births, umbilical cord blood (UCB) is considered to be the most plentiful reservoir of cells and to have regenerative potential for many clinical applications. Although UCB is used mainly against blood disorders, the spectrum of diseases for which it provides effective therapy has been expanded to include non-hematopoietic conditions; UCB has also been used as source for regenerative cell therapy and immune modulation. Thus, collection and banking of UCB-derived cells have become a popular option. However, there are questions regarding the cost versus the benefits of UCB banking, and it also raises complex ethical and legal issues. This review discusses many issues surrounding the conservation of UCB-derived cells and the great potential and current clinical applications of UCB in an era of new therapies. In particular, we describe the practical issues inherent in UCB collection, processing, and long-term storage as well as the different types of 'stem' or progenitor cells circulating in UCB and their uses in multiple clinical settings. Given these considerations, the trend toward UCB will continue to provide growing assistance to health care worldwide. PMID- 26133759 TI - Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model. AB - We recently reported the protective effects of chlorogenic acid (CGA) in a transient middle cerebral artery occlusion (tMCAo) rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA) was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion) were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP)-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p.) dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB) leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema. PMID- 26133760 TI - Chemical Characterization of Different Sumac and Pomegranate Extracts Effective against Botrytis cinerea Rots. AB - Pomegranate (Punica granatum L.) peel and sumac (Rhus coriaria L.) fruit and leaf extracts were chemically characterized and their ability to inhibit table grape (cv. Italia) rots caused by Botrytis cinerea was evaluated on artificially inoculated berries. Different extraction methods were applied and extracts were characterized through Ultra Fast High Performance Liquid Chromatography coupled to Photodiode array detector and Electrospray ionization Mass spectrometer (UPLC PDA-ESI/MSn) for their phenol and anthocyanin contents. The concentrated pomegranate peel extract (PGE-C) was the richest in phenols (66.97 g gallic acid equivalents/kg) while the concentrated sumac extract from fruits (SUF-C) showed the highest anthocyanin amount (171.96 mg cyanidin 3-glucoside equivalents/kg). Both phenolic and anthocyanin profile of pomegranate and sumac extracts were quite different: pomegranate extract was rich in cyanidin 3-glucoside, pelargonidin 3-glucoside and ellagic acid derivatives, while sumac extract was characterized by 7-methyl-cyanidin 3-galactoside and gallic acid derivatives. The concentrated extracts from both pomegranate peel and sumac leaves significantly reduced the development of Botrytis rots. In particular, the extract from pomegranate peel completely inhibited the pathogen at different intervals of time (0, 12, and 24 h) between treatment and pathogen inoculation on fruits maintained at 22-24 degrees C and high relative humidity (RH). This extract may represent a valuable alternative to control postharvest fungal rots in view of its high efficacy because of the low cost of pomegranate peel, which is a waste product of processing factories. PMID- 26133761 TI - A Highlight of Recent Advances in Aptamer Technology and Its Application. AB - Aptamers and SELEX (systematic evolution of ligands by exponential enrichment) technology have gained increasing attention over the past 25 years. Despite their functional similarity to protein antibodies, oligonucleotide aptamers have many unique properties that are suitable for clinical applications and industrialization. Aptamers may be superior to antibodies in fields such as biomarker discovery, in vitro and in vivo diagnosis, precisely controlled drug release, and targeted therapy. However, aptamer commercialization has not occurred as quickly as expected, and few aptamer-based products have yet successfully entered clinical and industrial use. Thus, it is important to critically review some technical barriers of aptamer and SELEX technology per se that may impede aptamer development and application. To date, how to rapidly obtain aptamers with superior bioavailability over antibodies remains the key issue. In this review, we discuss different chemical and structural modification strategies aimed to enhance aptamer bioavailability. We also discuss improvements to SELEX process steps to shorten the selection period and improve the SELEX process success rate. Applications in which aptamers are particularly suited and perform differently or superior to antibodies are briefly introduced. PMID- 26133762 TI - Induction of Mitochondrial Dependent Apoptosis in Human Leukemia K562 Cells by Meconopsis integrifolia: A Species from Traditional Tibetan Medicine. AB - OBJECTIVES: Meconopsis integrifolia (M. integrifolia) is one of the most popular members in Traditional Tibetan Medicine. This study aimed to investigate the anticancer effect of M. integrifolia and to detect the underlying mechanisms of these effects. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and trypan blue assay were used to evaluate the cytotoxicity of M. integrifolia. Changes in cell nuclear morphology and reactive oxygen species (ROS) level were observed by fluorescent microscopy. Apoptosis ratio, DNA damage and mitochondrial membrane potential (MMP) loss were analyzed by flow cytometry. Western blotting assay was adopted to detect the proteins related to apoptosis. Immunofluorescence was used to observe the release of cytochrome C. RESULTS: The obtained data revealed that M. integrifolia could significantly inhibit K562 cell viability, mainly by targeting apoptosis induction and cell cycle arrest in G2/M phase. Collapse in cell morphology, chromatin condensation, DNA damage and ROS accumulation were observed. Further mechanism detection revealed that mitochondrion might be a key factor in M. integrifolia-induced apoptosis. CONCLUSIONS: M. integrifolia could induce mitochondria mediated apoptosis and cell cycle arrest in G2/M phase with little damage to normal cells, suggesting that M. integrifolia might be a potential and efficient anticancer agent that deserves further investigation. PMID- 26133763 TI - Synthesis and Biological Evaluation of Lipophilic 1,4-Naphthoquinone Derivatives against Human Cancer Cell Lines. AB - To examine the effect of hydrophobicity on the anticancer activity of 1,4 naphthoquinone derivatives, a series of compounds bearing a 2-O-alkyl-, 3-C-alkyl or 2/3-N-morpholinoalkyl group were synthesized and evaluated for their anticancer activity against five human cancer cell lines in vitro. The cytotoxicity of these derivatives was assayed against HT-29, SW480, HepG2, MCF-7 and HL-60 cells by the MTT assay. Among them, 2-hydroxy-3-farnesyl-1,4 naphthoquinone (11a) was found to be the most cytotoxic against these cell lines. Our results showed that the effectiveness of compound 11a may be attributed to its suppression of the survival of HT-29. Secondly, in the Hoechst 33258 staining test, compound 11a-treated cells exhibited nuclear condensation typical of apoptosis. Additionally, cell cycle analysis by flow cytometry indicated that compound 11a arrested HT-29 cells in the S phase. Furthermore, cell death detected by Annexin V-FITC/propidium iodide staining showed that compound 11a efficiently induced apoptosis of HT-29 in a concentration-dependent manner. Taken together, compound 11a effectively inhibits colon cancer cell proliferation and may be a potent anticancer agent. PMID- 26133764 TI - Effect of a Bromo Substituent on the Glutathione Peroxidase Activity of a Pyridoxine-like Diselenide. AB - In search for better mimics of the glutathione peroxidase enzymes, pyridoxine like diselenides 6 and 11, carrying a 6-bromo substituent, were prepared. Reaction of 2,6-dibromo-3-pyridinol 5 with sodium diselenide provided 6 via aromatic nucleophilic substitution of the 2-bromo substituent. LiAlH4 caused reduction of all four ester groups and returned 11 after acidic workup. The X-ray structure of 6 showed that the dipyridyl diselenide moiety was kept in an almost planar, transoid conformation. According to NBO-analysis, this was due to weak intramolecular Se...O (1.1 kcal/mol) and Se...N-interactions (2.5 kcal/mol). That the 6-bromo substituent increased the positive charge on selenium was confirmed by NPA-analysis and seen in calculated and observed (77)Se NMR-shifts. Diselenide 6 showed a more than 3-fold higher reactivity than the corresponding des-bromo compound 3a and ebselen when evaluated in the coupled reductase assay. Experiments followed for longer time (2 h) confirmed that diselenide 6 is a better GPx-catalyst than 11. On the basis of (77)Se-NMR experiments, a catalytic mechanism for diselenide 6 was proposed involving selenol, selenosulfide and seleninic acid intermediates. At low concentration (10 MUM) where it showed only minimal toxicity, it could scavenge ROS produced by MNC- and PMNC-cells more efficiently than Trolox. PMID- 26133765 TI - Evaluating Positron Emission Tomography Use in Differentiated Thyroid Cancer. AB - BACKGROUND: Using the Surveillance, Epidemiology, and End Results-Medicare database, a substantial increase was found in the use of positron emission tomography (PET) scans after 2004 in differentiated thyroid cancer (DTC) patients. The reason for the increased utilization of the PET scan was not clear based on available the data. Therefore, the indications for and outcomes of PET scans performed at an academic institution were evaluated. METHODS: A retrospective cohort study was performed of DTC patients who underwent surgery at the University of Michigan Health System from 2006 to 2011. After identifying patients who underwent a PET scan, indications, rate of positive PET scans, and impact on management were evaluated. For positive scans, the location of disease was characterized, and presence of disease on other imaging was determined. RESULTS: Of the 585 patients in the cohort, 111 (19%) patients had 200 PET scans performed for evaluation of DTC. Indications for PET scan included: elevated thyroglobulin and negative radioiodine scan in 52 scans (26.0%), thyroglobulin antibodies in 13 scans (6.5%), rising thyroglobulin in 18 scans (9.0%), evaluation of abnormality on other imaging in 22 scans (11.0%), evaluation of extent of disease in 33 scans (16.5%), follow-up of previous scan in 57 scans (28.5%), other indications in two scans (1.0%), and unclear indications in three scans (1.5%). The PET scan was positive in 124 studies (62.0%); positivity was identified in the thyroid bed on 25 scans, cervical or mediastinal lymph nodes on 105 scans, lung on 28 scans, bone on four scans, and other areas on 14 scans. Therapy following PET scan was surgery in 66 cases (33.0%), chemotherapy or radiation in 23 cases (11.5%), observation in 110 cases (55.0%), and palliative care in one case (0.5%). Disease was identifiable on other imaging in 66% of cases. PET scan results changed management in 59 cases (29.5%). CONCLUSIONS: In this academic medical center, the PET scan was utilized in 19% of patients. Indications for the PET scan included conventional indications, such as elevated thyroglobulin with noniodine avid disease, and more controversial uses, such as evaluation of extent of disease or abnormalities on other imaging tests. PET scan results changed management in about 30% of cases. PMID- 26133766 TI - Is there association between hyperdense middle cerebral artery sign on CT scan and time from stroke onset within the first 24-hours? AB - BACKGROUND: The hyperdense artery sign (HAS) on CT brain scan is an assumed radiological marker of acute intra-arterial thrombotic occlusion. However, the relationship between HAS between time of stroke onset has not been adequately investigated, leading to uncertainty regarding its validity as a marker of acute ischaemia. We attempted to determine if the presence of the hyperdense artery sign is associated with time from stroke onset. METHODS: Retrospective cross sectional study conducted in a tertiary referral centre. Consecutive patients with acute ischaemic stroke and confirmed middle cerebral arterial occlusion on initial CT angiogram from 2007-2011 were included. Visual estimation and manual measurement of Hounsfield units of affected and corresponding non-affected artery on non-contrast CT was completed and mean density was calculated from four separate readings. Primary outcome measures were Time from stroke onset and HAS on both visual estimation and the ratio of mean value in Hounsfield Units (HU) of affected to non-affected artery. RESULTS: One hundred and fifty-four subjects with confirmed arterial occlusion on CT Angiogram were included in the study. There were no significant differences in age distribution or vascular risk factor presence between subjects with or without HAS. Subjects with HAS were less likely to be male (50.9% vs 70.8%, p = 0.02).) HAS was found in 106 (68.8%) of all subjects. Median NIHSS score at presentation was significantly higher in the HAS group (17 vs 12, p = 0.02). No statistically significant association between HAS and stroke onset time or density ratio between affected and non-affected artery was detected overall within either the first 24-h or on subgroup analysis of those in the first 4.5-h. A small subgroup of three patients with stroke onset greater than 24-h all had absent HAS. CONCLUSIONS: No evidence of a correlation between time of stroke onset and presence of a HAS within the first 24-h post acute ischaemic stroke was identified. The HAS was associated with a higher NIHSS score at presentation. PMID- 26133767 TI - Pancreaticogastrostomy in pure laparoscopic pancreaticoduodenectomy--A novel pancreatic-gastric anastomosis technique. AB - BACKGROUND: Although many surgical procedures are now routinely performed laparoscopically, pure laparoscopic pancreaticoduodenectomy (LPD) is not commonly performed because of the technical difficulty of pancreatic resection and the associated reconstruction procedures. Several pancreatic-enteric anastomosis techniques for LPD have been reported, but most are adaptations of open procedures. To accomplish pure LPD, we consider it necessary to establish new pancreatic-enteric anastomosis techniques that are specifically developed for LPD and are safe and feasible to perform. RESULTS: One patient developed a postoperative pancreatic fistula (International Study Group of Pancreatic Fistula criteria, grade B) and subsequent postoperative delayed gastric emptying (International Study Group of Pancreatic Surgery criteria, grade C). No other major complications occurred. We developed a novel pancreatic-gastric anastomosis technique that enabled us to safely perform pure LPD. The main pancreatic duct was stented with a 4-Fr polyvinyl catheter during pancreatic resection. A small hole was created in the posterior wall of the stomach and was bluntly dilated. A 5-cm incision was made in the anterior stomach, and the pancreatic drainage tube was passed into the stomach through the hole in the posterior wall. The remnant pancreas was pulled into the stomach, and was easily positioned and secured in place with only four to six sutures between the pancreatic capsule and the gastric mucosa. We used this technique to perform pure LPD in five patients between December 2012 and July 2013. CONCLUSIONS: Our new technique is technically easy and provides secure fixation between the gastric wall and the pancreas. This technique does not require main pancreatic duct dilatation, and the risk of intra-abdominal abscess formation due to postoperative pancreatic fistula may be minimized. Although this technique requires further investigation as it may increase the risk of delayed gastric emptying, it may be a useful method of performing pancreaticogastrostomy in pure LPD. TRIAL REGISTRATION: ISRCTN16761283 . Registered 16 January 2015. PMID- 26133768 TI - Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests. AB - The quality of diets in rodent feeding trials is crucial. We describe the contamination with environmental pollutants of 13 laboratory rodent diets from 5 continents. Measurements were performed using accredited methodologies. All diets were contaminated with pesticides (1-6 out of 262 measured), heavy metals (2-3 out of 4, mostly lead and cadmium), PCDD/Fs (1-13 out of 17) and PCBs (5-15 out of 18). Out of 22 GMOs tested for, Roundup-tolerant GMOs were the most frequently detected, constituting up to 48% of the diet. The main pesticide detected was Roundup, with residues of glyphosate and AMPA in 9 of the 13 diets, up to 370 ppb. The levels correlated with the amount of Roundup-tolerant GMOs. Toxic effects of these pollutants on liver, neurodevelopment, and reproduction are documented. The sum of the hazard quotients of the pollutants in the diets (an estimator of risk with a threshold of 1) varied from 15.8 to 40.5. Thus the chronic consumption of these diets can be considered at risk. Efforts toward safer diets will improve the reliability of toxicity tests in biomedical research and regulatory toxicology. PMID- 26133769 TI - A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile. AB - BACKGROUND: The incidence of pancreatic cancer (PC) continues to increase in the world, while most patients are diagnosed with advanced stages and survive <12 months. This poor prognosis is attributable to difficulty of early detection. Here we developed and evaluated a multivariate index composed of plasma free amino acids (PFAAs) for early detection of PC. METHODS: We conducted a cross sectional study in multi-institutions in Japan. Fasting plasma samples from PC patients (n = 360), chronic pancreatitis (CP) patients (n = 28), and healthy control (HC) subjects (n = 8372) without apparent cancers who were undergoing comprehensive medical examinations were collected. Concentrations of 19 PFAAs were measured by liquid chromatography-mass spectrometry. We generated an index consisting of the following six PFAAs: serine, asparagine, isoleucine, alanine, histidine, and tryptophan as variables for discrimination in a training set (120 PC and matching 600 HC) and evaluation in a validation set (240 PC, 28 CP, and 7772 HC). RESULTS: Several amino acid concentrations in plasma were significantly altered in PC. Plasma tryptophan and histidine concentrations in PC were particularly low, while serine was particularly higher than that of HC. The area under curve (AUC) based on receiver operating characteristic (ROC) curve analysis of the resulting index to discriminate PC from HC were 0.89 [95% confidence interval (CI), 0.86-0.93] in the training set. In the validation set, AUCs based on ROC curve analysis of the PFAA index were 0.86 (95% CI, 0.84-0.89) for all PC patients versus HC subjects, 0.81 (95% CI, 0.75-0.86) for PC patients from stage IIA to IIB versus HC subjects, and 0.87 (95% CI, 0.80-0.93) for all PC patients versus CP patients. CONCLUSIONS: These findings suggest that the PFAA profile of PC was significantly different from that of HC. The PFAA index is a promising biomarker for screening and diagnosis of PC. PMID- 26133770 TI - Phenylbutyrate Is Bacteriostatic against Mycobacterium tuberculosis and Regulates the Macrophage Response to Infection, Synergistically with 25-Hydroxy-Vitamin D3. AB - Adjunctive vitamin D treatment for pulmonary tuberculosis enhances resolution of inflammation but has modest effects on bacterial clearance. Sodium 4 phenylbutyrate (PBA) is in clinical use for a range of conditions and has been shown to synergise with vitamin D metabolites to upregulate cathelicidin antimicrobial peptide (CAMP) expression. We investigated whether clinically attainable plasma concentrations of PBA (0.4-4 mM) directly affect Mycobacterium tuberculosis (Mtb) growth and human macrophage and PBMC response to infection. We also tested the ability of PBA to enhance the immunomodulatory actions of the vitamin D metabolite 25(OH)D3 during infection and synergistically inhibit intracellular Mtb growth. PBA inhibited Mtb growth in broth with an MIC99 of 1 mM, which was reduced to 0.25 mM by lowering pH. During human macrophage infection, PBA treatment restricted Mtb uptake, phagocytic receptor expression and intracellular growth in a dose-dependent manner. PBA independently regulated CCL chemokine secretion and induced expression of the antimicrobial LTF (lactoferrin), the anti-inflammatory PROC (protein C) and multiple genes within the NLRP3 inflammasome pathway. PBA co-treatment with 25(OH)D3 synergistically modulated expression of numerous vitamin D-response genes, including CAMP, CYP24A1, CXCL10 and IL-37. This synergistic effect was dependent on MAPK signalling, while the effect of PBA on LTF, PROC and NLRP3 was MAPK-independent. During PBA and 25(OH)D3 co-treatment of human macrophages, in the absence of exogenous proteinase 3 (PR3) to activate cathelicidin, Mtb growth restriction was dominated by the effect of PBA, while the addition of PR3 enhanced growth restriction by 25(OH)D3 and PBA co-treatment. This suggests that PBA augments vitamin D-mediated cathelicidin-dependent Mtb growth restriction by human macrophages and independently induces antimicrobial and anti-inflammatory action. Therefore through both host-directed and bacterial-directed mechanisms PBA and vitamin D may prove an effective combinatorial adjunct therapy for tuberculosis to both resolve immunopathology and enhance bacterial clearance. PMID- 26133771 TI - Interference and Mechanism of Dill Seed Essential Oil and Contribution of Carvone and Limonene in Preventing Sclerotinia Rot of Rapeseed. AB - This study aimed to evaluate the inhibitory effects of dill (Anethum graveolens L.) seed essential oil against Sclerotinia sclerotiorum and its mechanism of action. The antifungal activities of the two main constituents, namely carvone and limonene, were also measured. Mycelial growth and sclerotial germination were thoroughly inhibited by dill seed essential oil at the 1.00 MUL/mL under contact condition and 0.125MUL/mL air under vapor condition. Carvone also contributed more than limonene in inhibiting the growth of S. sclerotiorum. Carvone and limonene synergistically inhibited the growth of the fungus. In vivo experiments, the essential oil remarkably suppressed S. sclerotiorum, and considerable morphological alterations were observed in the hyphae and sclerotia. Inhibition of ergosterol synthesis, malate dehydrogenase, succinate dehydrogenase activities, and external medium acidification were investigated to elucidate the antifungal mechanism of the essential oil. The seed essential oil of A. graveolens can be extensively used in agriculture for preventing the oilseed crops fungal disease. PMID- 26133772 TI - PIG3 plays an oncogenic role in papillary thyroid cancer by activating the PI3K/AKT/PTEN pathway. AB - The p53-inducible gene 3 (PIG3 or TP53I3) is a downstream gene of p53, which can be involved in the process of apoptosis induced by p53 via the production of reactive oxygen species (ROS). However, the functional significance of PIG3 in cancer remains to be determined. This aim of this study was to examine the mRNA and protein expression of PIG3 in papillary thyroid carcinoma (PTC) and normal thyroid tissues, assess the relationship between PIG3 expression and clinicopathological parameters in PTC and examine its role in the proliferation of PTC cell lines. The results showed that PIG3 was aberrantly overexpressed in the majority of specimens of PTC while the expression of p53 was lower in PTC compared with normal thyroid tissues. Anti-PIG3 immuno-reactivity positively correlated with TNM grade. In the PTC cell lines, PIG3 silencing using small interfering RNA (siRNAs) impaired their ability of proliferation and decreased the activity of the PI3K/AKT/PTEN pathway. The results suggested that PIG3 plays an oncogenic role in PTC via the regulation of the PI3K/AKT/PTEN pathway and support the exploration of PIG3 as a novel biomarker for patients with PTC. PMID- 26133774 TI - CCR 20th Anniversary Commentary: Paving the Way for Circulating Tumor Cells. AB - Cancer cells can enter the bloodstream, form distant metastases, and ultimately lead to death. A study by Allard and colleagues, which was published in the October 15, 2004, issue of Clinical Cancer Research, concluded that the CellSearch system could be used as a reliable tool to investigate circulating tumor cells and their clinical utility, and it spurred a still-growing interest in the field. PMID- 26133776 TI - Replication of Genetic Polymorphisms Reported to Be Associated with Taxane Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel--letter. PMID- 26133775 TI - Molecular Pathways: Overcoming Radiation Resistance by Targeting DNA Damage Response Pathways. AB - DNA double-strand breaks are the critical lesions responsible for the majority of ionizing radiation-induced cell killing. Thus, the ability of tumor cells to elicit a DNA damage response following radiation, via activation of DNA repair and cell-cycle checkpoints, promotes radiation resistance and tumor cell survival. Consequently, agents that target these DNA damage response pathways are being developed to overcome radiation resistance. Overall, these agents are effective radiosensitizers; however, their mechanisms of tumor cell selectivity are not fully elucidated. In this review, we focus on the crucial radiation induced DNA damage responses as well as clinical and translational advances with agents designed to inhibit these responses. Importantly, we describe how synthetic lethality can provide tumor cell-selective radiosensitization by these agents and expand the therapeutic window for DNA damage response-targeted agents used in combination with radiotherapy. PMID- 26133778 TI - Correction: Low Levels of Her2/neu Expressed by Ewing's Family Tumor Cell Lines Can Redirect Cytokine-Induced Killer Cells. AB - In this article (Clin Cancer Res 2005;11:4561-70), which was published in the June 15, 2005, issue of Clinical Cancer Research (1), one of the authors' names was misprinted. The corrected name should read as follows: "Mobin Karimi." The publisher regrets this error. PMID- 26133777 TI - Replication of Genetic Polymorphisms Reported to Be Associated with Taxane Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel--response. PMID- 26133779 TI - Correction: Survivin as a Prognostic Marker for Urothelial Carcinoma of the Bladder: A Multicenter External Validation Study. AB - In this article (Clin Cancer Res 2009;15:7012-9), which was published in the November 15, 2009, issue of Clinical Cancer Research (1), the study support was incorrectly listed as "NIH T32 training grant T32CA082088." The article did not receive NIH support. The correct support listing should read as follows: "Departmental support from the University of Texas Southwestern Medical Center." The authors regret this error. PMID- 26133780 TI - Long-term evaluation of ink clearance in tattoos with different color intensity using the 1064-nm Q-switched Nd:YAG laser. AB - OBJECTIVE: The aim of the study was to evaluate the efficacy of tattoo removal treatments using the 1064-nm Q-switched (QS) Nd:YAG laser. BACKGROUND DATA: Today, QS lasers appear to be the most common, effective, and safest methods to treat unwanted markings. MATERIAL AND METHODS: A total of 64 patients with 75 unwanted tattoos were enrolled in the study. Tattoo clearance was evaluated according to the color intensity - concentration of pigment: group I (34) - black; group II (41) - gray. Consideration included methods of tattooing and tattoo techniques. RESULTS: In group I, after the first treatment session the median of clearance was 30% (10-50%), while in group II, the median was 50% (40 70%). After the second treatment session, median in group I increased to 40% (30 50%). Median of group II increased to 70% (50-80%). The highest number of treatment in group I was 7. After that, the median grew to 75%, while the highest amount of treatment in group II was 5 and a median of 90% was achieved. CONCLUSIONS: Effects were dependent upon the amount of ink deposited in the tissue. Old amateur tattoos and tattoos containing small quantities of ink (technique: shading and lines) demonstrated the quickest and the most efficacious results. Tattoos with large quantities of ink, obtained by filling, required the greatest number of treatment sessions. The final outcome in tattoo clearing can only be assessed following treatment completion, which may in some cases take 2-3 years. Presumably, in some cases, complete clearance is impossible. PMID- 26133782 TI - Different Effects of Regional Species Pool on Plant Diversity between Forest and Grassland Biomes in Arid Northwest China. AB - Species pool hypothesis is broadly known and frequently tested in various regions and vegetation types. However it has not been tested in the arid Xinjiang region of China due to lack of data. Here with systematic data from references and field survey, we comprehensively examined species pool hypothesis in this region. Took species richness in 0.1 degrees * 0.1 degrees grid cells as regional species richness (RSR) which were obtained from the distribution maps of vascular plant species, and took species diversity of 190 and 103 plots in forest and grassland biomes across Xinjiang as local species richness (LSR), together with the digitalized soil pH and climate data, we tested the species pool hypothesis in this region. We found that: (1) the average RSR was higher in mountains than that in basins and it was negatively correlated with soil pH in mountains while positively correlated with soil pH in basins in Xinjiang; (2) RSR showed a positive correlation with mean annual precipitation (MAP) while showed a hump shaped pattern with mean annual temperature (MAT); and the changing patterns of LSR were different for forest and grassland along the geographical and climate gradients; (3) LSR of forest was more affected by RSR than by climate, while on the contrary, LSR of grassland was more affected by climate than by RSR. Our results validated the species pool hypothesis in revealing that RSR had a significant role in shaping LSR patterns in addition to climate. We concluded that the relative effects of climate vs. RSR on LSR differed markedly between the forest and grassland communities across Xinjiang. Our results also showed that RSR revealed a contrasting relationship with soil pH in mountains and in basins, which might reflect differences in evolutionary processes of various habitats. In summary, our research systematically analyzed the correlation of species richness in regional and local scales in Xinjiang which provides more insights into the understanding of species pool hypothesis. PMID- 26133781 TI - Effects of Endocrine Disruptor Compounds, Alone or in Combination, on Human Macrophage-Like THP-1 Cell Response. AB - The aim of the present study was to evaluate the immunological effects on human macrophages of four endocrine disruptor compounds (EDCs) using the differentiated human THP-1 cell line as a model. We studied first the effects of these EDCs, including Bisphenol A (BPA), di-ethylhexyl-phthalate (DEHP), dibutyl phthalate (DBP) and 4-tert-octylphenol (4-OP), either alone or in combination, on cytokine secretion, and phagocytosis. We then determined whether or not these effects were mediated by estrogen receptors via MAPK pathways. It was found that all four EDCs studied reduced strongly the phagocytosis of the differentiated THP-1 cells and that several of these EDCs disturbed also TNF-alpha, IL-1 beta and IL-8 cytokine secretions. Furthermore, relative to control treatment, decreased ERK 1/2 phosphorylation was always associated with EDCs treatments-either alone or in certain combinations (at 0.1 MUM for each condition). Lastly, as treatments by an estrogen receptor antagonist suppressed the negative effects on ERK 1/2 phosphorylation observed in cells treated either alone with BPA, DEHP, 4-OP or with the combined treatment of BPA and DEHP, we suggested that estrogen receptor dependent pathway is involved in mediating the effects of EDCs on human immune system. Altogether, these results advocate that EDCs can disturb human immune response at very low concentrations. PMID- 26133784 TI - Time-based position estimation in monolithic scintillator detectors. AB - Gamma-ray detectors based on bright monolithic scintillation crystals coupled to pixelated photodetectors are currently being considered for several applications in the medical imaging field. In a typical monolithic detector, both the light intensity and the time of arrival of the earliest scintillation photons can be recorded by each of the photosensor pixels every time a gamma interaction occurs. Generally, the time stamps are used to determine the gamma interaction time while the light intensities are used to estimate the 3D position of the interaction point. In this work we show that the spatio-temporal distribution of the time stamps also carries information on the location of the gamma interaction point and thus the time stamps can be used as explanatory variables for position estimation. We present a model for the spatial resolution obtainable when the interaction position is estimated using exclusively the time stamp of the first photon detected on each of the photosensor pixels. The model is shown to be in agreement with experimental measurements on a 16 mm * 16 mm * 10 mm LSO : Ce,0.2%Ca crystal coupled to a digital photon counter (DPC) array where a spatial resolution of 3 mm (root mean squared error) is obtained. Finally we discuss the effects of the main parameters such as scintillator rise and decay time, light output and photosensor single photon time resolution and pixel size. PMID- 26133783 TI - Transcriptome Profiling of Tomato Fruit Development Reveals Transcription Factors Associated with Ascorbic Acid, Carotenoid and Flavonoid Biosynthesis. AB - Tomato (Solanum lycopersicum) serves as a research model for fruit development; however, while it is an important dietary source of antioxidant nutrients, the transcriptional regulation of genes that determine nutrient levels remains poorly understood. Here, the transcriptomes of fruit at seven developmental stages (7, 14, 21, 28, 35, 42 and 49 days after flowering) from two tomato cultivars (Ailsa Craig and HG6-61) were evaluated using the Illumina sequencing platform. A total of 26,397 genes, which were expressed in at least one developmental stage, were detected in the two cultivars, and the expression patterns of those genes could be divided into 20 groups using a K-mean cluster analysis. Gene Ontology term enrichment analysis indicated that genes involved in RNA regulation, secondary metabolism, hormone metabolism and cell wall metabolism were the most highly differentially expressed genes during fruit development and ripening. A co expression analysis revealed several transcription factors whose expression patterns correlated with those of genes associated with ascorbic acid, carotenoid and flavonoid biosynthesis. This transcriptional correlation was confirmed by agroinfiltration mediated transient expression, which showed that most of the enzymatic genes in the ascorbic acid biosynthesis were regulated by the overexpression of each of the three transcription factors that were tested. The metabolic dynamics of ascorbic acid, carotenoid and flavonoid were investigated during fruit development and ripening, and some selected transcription factors showed transcriptional correlation with the accumulation of ascorbic acid, carotenoid and flavonoid. This transcriptome study provides insight into the regulatory mechanism of fruit development and presents candidate transcription factors involved in secondary metabolism. PMID- 26133786 TI - Upregulation of microRNA-335 and microRNA-584 contributes to the pathogenesis of severe preeclampsia through downregulation of endothelial nitric oxide synthase. AB - The aim of the present study was to identify the differentially expressed microRNAs (miRNAs) in placenta from patients with preeclampsia, and examine their roles in the pathogenesis of preeclampsia in vivo and ex vivo. The placental expression levels of miRNAs were examined in tissue samples harvested from 20 patients with preeclampsia and 20 healthy control individuals. A total of 18 miRNAs were differentially expressed (12 upregulated and six downregulated) among the preeclampsia cases, compared with the controls. By further functional/pathway analysis, two significantly upregulated miRNAs, miR-335 and miR-584, were identified. These target endothelial nitric oxide synthase (eNOS), which has been repeatedly reported to be involved in the development of preeclampsia. The present study then verified eNOS as a target gene of miR-335 and miR-584 using a luceriferase assay, and confirmed the expression patterns of the two miRNAs and eNOS in preeclampsic and normal placentas. Additionally, to examine the function of miR-584 and miR-335 in human placenta, the present study transiently transfected the HTR8/Svneo cell line with miR-584 and miR-335 mimics or their inhibitors, and the results of a subsequent Transwell insert invasion assay revealed that miR-584 and miR-335 inhibited the migratory ability of the trophoblast cells, and that the effect was 'rescued' by overexpressed eNOS. These data revealed a negative regulatory role of miR-584 and miR-335 in the migration of HTR-8/SVneo cells by targeting eNOS, and identified miR-584 and miR-335 as potential novel therapeutic targets in preeclampsia. PMID- 26133788 TI - Correction to Electrochemical Detection of Low Concentrations of Mercury in Water Using Gold Nanoparticles. PMID- 26133785 TI - miR-16 rescues F508del-CFTR function in native cystic fibrosis epithelial cells. AB - Cystic fibrosis (CF) is due to mutations in the CFTR gene, which prevents correct folding, trafficking and function of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. The dysfunctional effect of CFTR mutations, principally the F508del-CFTR mutant, is further manifested by hypersecretion of the pro-inflammatory chemokine interleukin-8 into the airway lumen, which further contributes to morbidity and mortality. We have hypothesized that microRNA (miR) based therapeutics could rescue the dysfunctional consequences of mutant CFTR. Here we report that a miR-16 mimic can effectively rescue F508del-CFTR protein function in airway cell lines and primary cultures, of differentiated human bronchial epithelia from F508del homozygotes, which express mutant CFTR endogenously. We also identify two other miRs, miR-1 and miR-302a, which are also active. Although miR-16 is expressed at basal comparable levels in CF and control cells, miR-1 and miR-302a are undetectable. When miR mimics are expressed in CF lung or pancreatic cells, the expression of the F508del-CFTR protein is significantly increased. Importantly, miR-16 promotes functional rescue of the cyclic AMP-activated apical F508del-CFTR chloride channel in primary lung epithelial cells from CF patients. We interpret these findings to suggest that these miRs may constitute novel targets for CF therapy. PMID- 26133787 TI - Tissue Transglutaminase contributes to experimental multiple sclerosis pathogenesis and clinical outcome by promoting macrophage migration. AB - Multiple sclerosis is a serious neurological disorder, resulting in e.g., sensory, motor and cognitive deficits. A critical pathological aspect of multiple sclerosis (MS) is the influx of immunomodulatory cells into the central nervous system (CNS). Identification of key players that regulate cellular trafficking into the CNS may lead to the development of more selective treatment to halt this process. The multifunctional enzyme tissue Transglutaminase (TG2) can participate in various inflammation-related processes, and is known to be expressed in the CNS. In the present study, we question whether TG2 activity contributes to the pathogenesis of experimental MS, and could be a novel therapeutic target. In human post-mortem material, we showed the appearance of TG2 immunoreactivity in leukocytes in MS lesions, and particular in macrophages in rat chronic-relapsing experimental autoimmune encephalomyelitis (cr-EAE), an experimental MS model. Clinical deficits as observed in mouse EAE were reduced in TG2 knock-out mice compared to littermate wild-type mice, supporting a role of TG2 in EAE pathogenesis. To establish if the enzyme TG2 represents an attractive therapeutic target, cr-EAE rats were treated with TG2 activity inhibitors during ongoing disease. Reduction of TG2 activity in cr-EAE animals dramatically attenuated clinical deficits and demyelination. The mechanism underlying these beneficial effects pointed toward a reduction in macrophage migration into the CNS due to attenuated cytoskeletal flexibility and RhoA GTPase activity. Moreover, iNOS and TNFalpha levels were selectively reduced in the CNS of cr-EAE rats treated with a TG2 activity inhibitor, whereas other relevant inflammatory mediators were not affected in CNS or spleen by reducing TG2 activity. We conclude that modulating TG2 activity opens new avenues for therapeutic intervention in MS which does not affect peripheral levels of inflammatory mediators. PMID- 26133789 TI - Black Hydroxylated Titanium Dioxide Prepared via Ultrasonication with Enhanced Photocatalytic Activity. AB - The amorphous TiO2 derived from hydroxylation has become an effective approach for the enhancement of photocatalytic activity of TiO2 since a kind of special black TiO2 was prepared by engineering disordered layers on TiO2 nanocrystals via hydrogenation. In this contribution, we prepared totally amorphous TiO2 with various degrees of blackness by introducing hydroxyls via ultrasonic irradiation, through which can we remarkably enhance the photocatalytic activity of TiO2 with improved light harvesting and narrowed band gap. PMID- 26133790 TI - Diplopia and ocular motility in orbital blow-out fractures: 10-year retrospective study. AB - OBJECTIVE: To investigate diplopia (binocular single vision [BSV] test) and ocular motility (uniocular field of fixation [UFOF] test) characteristics in blow out fractures of the orbit and their value in fracture management. MATERIAL AND METHODS: Patients with isolated blow-out fractures treated from 2000 to 2010 were included. BSV scores were stratified into three categories: low BSV category (0 60); moderate BSV category (61-80), and high BSV category (81-100). UFOF scores were also divided into three categories: low score (60-240), moderate score (241 270), and high score (271-365) categories. RESULTS: A total of 183 patients (106 surgically and 77 conservatively managed) met the inclusion criteria. There was no significant improvement in BSV postoperatively in surgically managed patients with preoperatively high BSV, whereas there was significant improvement (p < 0.05) for the high BSV category in the conservative group. Preoperative BSV was found to be significantly related (p < 0.05) to postoperative BSV, subjective diplopia outcome, follow-up time, and number of follow-up visits. However, improvement of BSV score in the surgical group was not found to be significantly correlated with subjective outcome in relation to diplopia. Preoperative UFOF score has no influence on subjective outcome in relation to diplopia. Surgical timing, approach, and choice of implant material were not found to be statistically related to final diplopia outcome, follow-up time, or number of follow-up visits. CONCLUSIONS: BSV is better correlated with diplopia outcome, follow-up time, and number of follow-up visits than is UFOF. On the basis of this study, surgical intervention would not be recommended for blow-out fracture cases with BSV score >80% for correction of diplopia alone. PMID- 26133791 TI - Current rectification in a single molecule diode: the role of electrode coupling. AB - We demonstrate large rectification ratios (> 100) in single-molecule junctions based on a metal-oxide cluster (polyoxometalate), using a scanning tunneling microscope (STM) both at ambient conditions and at low temperature. These rectification ratios are the largest ever observed in a single-molecule junction, and in addition these junctions sustain current densities larger than 10(5) A cm( 2). By following the variation of the I-V characteristics with tip-molecule separation we demonstrate unambiguously that rectification is due to asymmetric coupling to the electrodes of a molecule with an asymmetric level structure. This mechanism can be implemented in other type of molecular junctions using both organic and inorganic molecules and provides a simple strategy for the rational design of molecular diodes. PMID- 26133792 TI - Hint1 knockout results in a compromised activation of protein kinase C gamma in the brain. AB - Previous studies have implicated a role of the histidine triad nucleotide-binding protein 1 (Hint1) in the pathogenesis of schizophrenia. Protein kinase C gamma (PKCgamma) could be potentially involved in the Hint1-implicated pathogenesis since PKCgamma was identified as a Hint1 interacting protein. Recently, a debate was brought forward from the understanding how Hint1 affects the expression and activity of PKCgamma in the brain. In the present study, we use Hint1 knockout mice and biochemical analysis to define the effect of Hint1 on protein PKCgamma. Our data reveal that Hint1-deficiency in mouse brains led to increased protein levels of PKCgamma in the cortex and hippocampus, the striatum and thalamus and amygdala. Without stimulation, PKCgamma protein in Hint1-deficient brain displayed a basal activity that was reflected by control-leveled phosphorylations of PKCgamma T514 and T674 at its kinase domain. Upon psycho-stimulation, both sites of PKCgamma T514 and T674 were activated in these brain structures via phosphorylation; however, the phosphorylation level at the site of PKCgamma T674 apparently attenuated in Hint1-deficient mice compared to wild-type control. Thus, we conclude that Hint1 deficiency leads to an increased protein level of PKCgamma in the brain and a compromised activation response of PKCgamma upon stimulation. These findings suggest an inhibitory role of Hint1 on the protein PKCgamma in the brain and an impaired PKCgamma-mediated phosphorylation signal in Hint1-deficient neuron. PMID- 26133793 TI - Central nervous system-specific knockout of Brg1 causes growth retardation and neuronal degeneration. AB - Changes in chromatin structure (chromatin remodeling) are essential regulatory processes for neuronal development, but the molecular mechanisms are unclear. The aim of the present study was to assess the effects of conditional knockout (Ko) of the Brahma-related gene-1 (Brg1) in the mouse central nervous system (CNS) on postnatal development. Brg1 was deleted in the CNS by crossing mice carrying the Brg1 conditional allele with a transgenic line expressing Cre under the control of the Nex 1 promoter. Brg1, PSD-95, NR2A and NR2B protein expressions were assessed using western blotting. Immunofluorescence, Nissl and TUNEL staining were used to assess cortical neuron viability. Hippocampal neurons were extracted from mouse embryos to observe the effects of neuronal degeneration associated with oxidative stress using Paraquat dichloride x-hydrate or 80% oxygen. Brg1(fx/fx);NEX-Cre mice were significantly smaller in both body size and brain size after P35 conditional Ko of Brg1 in mouse cortical progenitors. The amount of neurons and their dendritic branches were significantly reduced in Brg1 Ko cortexes during early postnatal development. Absence of Brg1 may result in increased number of astrocytes. Loss of Brg1 increased damaged and dying neurons associated with oxidative stress. Furthermore, loss of NR2A in the Brg1 Ko cortex during early postnatal development, and delayed the NR2B-NR2A switch. Therefore, Brg1 may play a critical role in neuronal growth by regulating the NR2B-NR2A switch. Our findings provide an insight in chromatin remodeling regulation in postnatal neuronal development. PMID- 26133794 TI - Activation of transcription factors STAT1 and STAT5 in the mouse median eminence after systemic ciliary neurotrophic factor administration. AB - Exogenously administered ciliary neurotrophic factor (CNTF) causes weight loss in obese rodents and humans through leptin-like activation of the Jak-STAT3 signaling pathway in hypothalamic arcuate neurons. Here we report for the first time that 40min after acute systemic treatment, rat recombinant CNTF (intraperitoneal injection of 0.3mg/kg of body weight) induced nuclear translocation of the tyrosine-phosphorylated forms of STAT1 and STAT5 in the mouse median eminence and other circumventricular organs, including the vascular organ of the lamina terminalis and the subfornical organ. In the tuberal hypothalamus of treated mice, specific nuclear immunostaining for phospo-STAT1 and phospho-STAT5 was detected in ependymal cells bordering the third ventricle floor and lateral recesses, and in median eminence cells. Co-localization studies documented STAT1 and STAT5 activation in median eminence beta-tanycytes and underlying radial glia-like cells. A few astrocytes in the arcuate nucleus responded to CNTF by STAT5 activation. The vast majority of median eminence tanycytes and radial glia-like cells showing phospho-STAT1 and phospho-STAT5 immunoreactivity were also positive for phospho-STAT3. In contrast, STAT3 was the sole STAT isoform activated by CNTF in arcuate nucleus and median eminence neurons. Finally, immunohistochemical evaluation of STAT activation 20, 40, 80, and 120min from the injection demonstrated that cell activation was accompanied by c-Fos expression. Collectively, our findings show that CNTF activates STAT3, STAT1, and STAT5 in vivo. The distinctive activation pattern of these STAT isoforms in the median eminence may disclose novel targets and pathways through which CNTF regulates food intake. PMID- 26133795 TI - Behavior and modeling of two-dimensional precedence effect in head-unrestrained cats. AB - The precedence effect (PE) is an auditory illusion that occurs when listeners localize nearly coincident and similar sounds from different spatial locations, such as a direct sound and its echo. It has mostly been studied in humans and animals with immobile heads in the horizontal plane; speaker pairs were often symmetrically located in the frontal hemifield. The present study examined the PE in head-unrestrained cats for a variety of paired-sound conditions along the horizontal, vertical, and diagonal axes. Cats were trained with operant conditioning to direct their gaze to the perceived sound location. Stereotypical PE-like behaviors were observed for speaker pairs placed in azimuth or diagonally in the frontal hemifield as the interstimulus delay was varied. For speaker pairs in the median sagittal plane, no clear PE-like behavior occurred. Interestingly, when speakers were placed diagonally in front of the cat, certain PE-like behavior emerged along the vertical dimension. However, PE-like behavior was not observed when both speakers were located in the left hemifield. A Hodgkin-Huxley model was used to simulate responses of neurons in the medial superior olive (MSO) to sound pairs in azimuth. The novel simulation incorporated a low threshold potassium current and frequency mismatches to generate internal delays. The model exhibited distinct PE-like behavior, such as summing localization and localization dominance. The simulation indicated that certain encoding of the PE could have occurred before information reaches the inferior colliculus, and MSO neurons with binaural inputs having mismatched characteristic frequencies may play an important role. PMID- 26133796 TI - Evidence for distinct brain networks in the control of rule-based motor behavior. AB - Reach guidance when the spatial location of the viewed target and hand movement are incongruent (i.e., decoupled) necessitates use of explicit cognitive rules (strategic control) or implicit recalibration of gaze and limb position (sensorimotor recalibration). In a patient with optic ataxia (OA) and bilateral superior parietal lobule damage, we recently demonstrated an increased reliance on strategic control when the patient performed a decoupled reach (Granek JA, Pisella L, Stemberger J, Vighetto A, Rossetti Y, Sergio LE. PLoS One 8: e86138, 2013). To more generally understand the fundamental mechanisms of decoupled visuomotor control and to more specifically test whether we could distinguish these two modes of movement control, we tested healthy participants in a cognitively demanding dual task. Participants continuously counted backward while simultaneously reaching toward horizontal (left or right) or diagonal (equivalent to top-left or top-right) targets with either veridical or rotated (90 degrees ) cursor feedback. By increasing the overall neural load and selectively compromising potentially overlapping neural circuits responsible for strategic control, the complex dual task served as a noninvasive means to disrupt the integration of a cognitive rule into a motor action. Complementary to our previous results observed in patients with optic ataxia, here our dual task led to greater performance deficits during movements that required an explicit rule, implying a selective disruption of strategic control in decoupled reaching. Our results suggest that distinct neural processing is required to control these different types of reaching because in considering the current results and previous patient results together, the two classes of movement could be differentiated depending on the type of interference. PMID- 26133797 TI - Single-unit activity, threshold crossings, and local field potentials in motor cortex differentially encode reach kinematics. AB - A diversity of signals can be recorded with extracellular electrodes. It remains unclear whether different signal types convey similar or different information and whether they capture the same or different underlying neural phenomena. Some researchers focus on spiking activity, while others examine local field potentials, and still others posit that these are fundamentally the same signals. We examined the similarities and differences in the information contained in four signal types recorded simultaneously from multielectrode arrays implanted in primary motor cortex: well-isolated action potentials from putative single units, multiunit threshold crossings, and local field potentials (LFPs) at two distinct frequency bands. We quantified the tuning of these signal types to kinematic parameters of reaching movements. We found 1) threshold crossing activity is not a proxy for single-unit activity; 2) when examined on individual electrodes, threshold crossing activity more closely resembles LFP activity at frequencies between 100 and 300 Hz than it does single-unit activity; 3) when examined across multiple electrodes, threshold crossing activity and LFP integrate neural activity at different spatial scales; and 4) LFP power in the "beta band" (between 10 and 40 Hz) is a reliable indicator of movement onset but does not encode kinematic features on an instant-by-instant basis. These results show that the diverse signals recorded from extracellular electrodes provide somewhat distinct and complementary information. It may be that these signal types arise from biological phenomena that are partially distinct. These results also have practical implications for harnessing richer signals to improve brain-machine interface control. PMID- 26133798 TI - pigk Mutation underlies macho behavior and affects Rohon-Beard cell excitability. AB - The study of touch-evoked behavior allows investigation of both the cells and circuits that generate a response to tactile stimulation. We investigate a touch insensitive zebrafish mutant, macho (maco), previously shown to have reduced sodium current amplitude and lack of action potential firing in sensory neurons. In the genomes of mutant but not wild-type embryos, we identify a mutation in the pigk gene. The encoded protein, PigK, functions in attachment of glycophosphatidylinositol anchors to precursor proteins. In wild-type embryos, pigk mRNA is present at times when mutant embryos display behavioral phenotypes. Consistent with the predicted loss of function induced by the mutation, knock down of PigK phenocopies maco touch insensitivity and leads to reduced sodium current (INa) amplitudes in sensory neurons. We further test whether the genetic defect in pigk underlies the maco phenotype by overexpressing wild-type pigk in mutant embryos. We find that ubiquitous expression of wild-type pigk rescues the touch response in maco mutants. In addition, for maco mutants, expression of wild type pigk restricted to sensory neurons rescues sodium current amplitudes and action potential firing in sensory neurons. However, expression of wild-type pigk limited to sensory cells of mutant embryos does not allow rescue of the behavioral touch response. Our results demonstrate an essential role for pigk in generation of the touch response beyond that required for maintenance of proper INa density and action potential firing in sensory neurons. PMID- 26133799 TI - Medial frontal ~4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion. AB - The temporal control of action is a highly conserved and critical mammalian behavior. Here, we investigate the neuronal basis of this process using an interval timing task. In rats and humans, instructional timing cues triggered spectral power across delta and theta bands (2-6 Hz) from the medial frontal cortex (MFC). Humans and rodents with dysfunctional dopamine have impaired interval timing, and we found that both humans with Parkinson's disease (PD) and rodents with local MFC dopamine depletion had attenuated delta and theta activity. In rodents, spectral activity in this range could functionally couple single MFC neurons involved in temporal processing. Without MFC dopamine, these neurons had less functional coupling with delta/theta activity and less temporal processing. Finally, in humans this 2- to 6-Hz activity was correlated with executive function in matched controls but not in PD patients. Collectively, these findings suggest that cue-evoked low-frequency rhythms could be a clinically important biomarker of PD that is translatable to rodent models, facilitating mechanistic inquiry and the development of neurophysiological biomarkers for human disease. PMID- 26133800 TI - Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients. AB - Facial flushing in rosacea is often induced by trigger events. However, trigger causation mechanisms are currently unclear. This study tested the central hypothesis that rosacea causes sympathetic and axon reflex-mediated alterations resulting in trigger-induced symptomatology. Twenty rosacea patients and age/sex matched controls participated in one or a combination of symptom triggering stressors. In protocol 1, forehead skin sympathetic nerve activity (SSNA; supraorbital microneurography) was measured during sympathoexcitatory mental (2 min serial subtraction of novel numbers) and physical (2-min isometric handgrip) stress. In protocol 2, forehead skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (capacitance hygrometry) were measured during sympathoexcitatory heat stress (whole body heating by perfusing 50 degrees C water through a tube-lined suit). In protocol 3, cheek, forehead, forearm, and palm skin blood flow were measured during nonpainful local heating to induce axon reflex vasodilation. Heart rate (HR) and mean arterial pressure (MAP) were recorded via finger photoplethysmography to calculate cutaneous vascular conductance (CVC; flux.100/MAP). Higher patient transepithelial water loss was observed (rosacea 0.20 +/- 0.02 vs. control 0.10 +/- 0.01 mg.cm(-2).min(-1), P < 0.05). HR and MAP changes were not different between groups during sympathoexcitatory stressors or local heating. SSNA during early mental (32 +/- 9 and 9 +/- 4% increase) and physical (25 +/- 4 and 5 +/- 1% increase, rosacea and controls, respectively) stress was augmented in rosacea (both P < 0.05). Heat stress induced more rapid sweating and cutaneous vasodilation onset in rosacea compared with controls. No axon reflex vasodilation differences were observed between groups. These data indicate that rosacea affects SSNA and that hyperresponsiveness to trigger events appears to have a sympathetic component. PMID- 26133801 TI - Brain activity mapping at multiple scales with silicon microprobes containing 1,024 electrodes. AB - The coordinated activity of neural ensembles across multiple interconnected regions has been challenging to study in the mammalian brain with cellular resolution using conventional recording tools. For instance, neural systems regulating learned behaviors often encompass multiple distinct structures that span the brain. To address this challenge we developed a three-dimensional (3D) silicon microprobe capable of simultaneously measuring extracellular spike and local field potential activity from 1,024 electrodes. The microprobe geometry can be precisely configured during assembly to target virtually any combination of four spatially distinct neuroanatomical planes. Here we report on the operation of such a device built for high-throughput monitoring of neural signals in the orbitofrontal cortex and several nuclei in the basal ganglia. We perform analysis on systems-level dynamics and correlations during periods of conditioned behavioral responding and rest, demonstrating the technology's ability to reveal functional organization at multiple scales in parallel in the mouse brain. PMID- 26133802 TI - Evidence for the initiation of decompression sickness by exposure to intense underwater sound. AB - Mass stranding of cetaceans (whales and dolphins), in close association with the activity of naval sonar systems, has been reported on numerous occasions. Necropsy showed bubble-associated lesions similar to those described in human decompression sickness (DCS). We examined the hypothesis that exposure to underwater sound may potentiate DCS. Rats were subjected to immersion and simulated dives with and without simultaneous acoustic transmissions at pressure levels and frequencies of 204 dB/8 kHz and 183.3 dB/15 kHz. DCS severity was assessed using the rotating wheel method. Recording of somatosensory evoked potentials (SSEPs) was employed under general anesthesia as an electrophysiological measure of neurologic insult. A significantly higher rate of decompression sickness was found among animals exposed to the 204-dB/8-kHz sound field. Significantly higher pathological SSEPs scores were noted for both underwater sound protocols. Pathological SSEPs scores in animals immersed during the acoustic transmissions, but without changes in ambient pressure, were comparable to those observed in animals exposed to the dive profile. The results demonstrate induction of neurological damage by intense underwater sound during immersion, with a further deleterious effect when this was combined with decompression stress. The study outcome has potential implications for human diving safety and may provide an explanation for the mass stranding of cetaceans purportedly associated with sonar activity. PMID- 26133803 TI - Hand interception of occluded motion in humans: a test of model-based vs. on-line control. AB - Two control schemes have been hypothesized for the manual interception of fast visual targets. In the model-free on-line control, extrapolation of target motion is based on continuous visual information, without resorting to physical models. In the model-based control, instead, a prior model of target motion predicts the future spatiotemporal trajectory. To distinguish between the two hypotheses in the case of projectile motion, we asked participants to hit a ball that rolled down an incline at 0.2 g and then fell in air at 1 g along a parabola. By varying starting position, ball velocity and trajectory differed between trials. Motion on the incline was always visible, whereas parabolic motion was either visible or occluded. We found that participants were equally successful at hitting the falling ball in both visible and occluded conditions. Moreover, in different trials the intersection points were distributed along the parabolic trajectories of the ball, indicating that subjects were able to extrapolate an extended segment of the target trajectory. Remarkably, this trend was observed even at the very first repetition of movements. These results are consistent with the hypothesis of model-based control, but not with on-line control. Indeed, ball path and speed during the occlusion could not be extrapolated solely from the kinematic information obtained during the preceding visible phase. The only way to extrapolate ball motion correctly during the occlusion was to assume that the ball would fall under gravity and air drag when hidden from view. Such an assumption had to be derived from prior experience. PMID- 26133805 TI - Trajectories and Determinants of Elder Care in Rural China During an 8-Year Period: Why Having Sons Makes a Difference. AB - Using 8-year panel data for 1,355 older adults in rural Anhui province, China, this study examined the trajectories and determinants of elder care provided by adult children to their older parents. The results of two-level latent variable growth models showed that trajectories of elder care differed by the gender of children, with an increase in care from sons but a decrease in care from daughters over time. Children's life stages influenced their care provision but differed by gender. Functional impairment of parents and care provided by siblings in the family also affected the care provided by each child. The findings reflect the patrilineal nature of Chinese family systems and demonstrate the linkages between critical life events and caregiving behaviors of adult children. Findings of this study can inform the formulation of elder care policies that meet the needs of families with different structures and at different life stages. PMID- 26133804 TI - Distinctive receptive field and physiological properties of a wide-field amacrine cell in the macaque monkey retina. AB - At early stages of visual processing, receptive fields are typically described as subtending local regions of space and thus performing computations on a narrow spatial scale. Nevertheless, stimulation well outside of the classical receptive field can exert clear and significant effects on visual processing. Given the distances over which they occur, the retinal mechanisms responsible for these long-range effects would certainly require signal propagation via active membrane properties. Here the physiology of a wide-field amacrine cell-the wiry cell-in macaque monkey retina is explored, revealing receptive fields that represent a striking departure from the classic structure. A single wiry cell integrates signals over wide regions of retina, 5-10 times larger than the classic receptive fields of most retinal ganglion cells. Wiry cells integrate signals over space much more effectively than predicted from passive signal propagation, and spatial integration is strongly attenuated during blockade of NMDA spikes but integration is insensitive to blockade of NaV channels with TTX. Thus these cells appear well suited for contributing to the long-range interactions of visual signals that characterize many aspects of visual perception. PMID- 26133806 TI - Accuracy of estimated breeding values with genomic information on males, females, or both: an example on broiler chicken. AB - BACKGROUND: As more and more genotypes become available, accuracy of genomic evaluations can potentially increase. However, the impact of genotype data on accuracy depends on the structure of the genotyped cohort. For populations such as dairy cattle, the greatest benefit has come from genotyping sires with high accuracy, whereas the benefit due to adding genotypes from cows was smaller. In broiler chicken breeding programs, males have less progeny than dairy bulls, females have more progeny than dairy cows, and most production traits are recorded for both sexes. Consequently, genotyping both sexes in broiler chickens may be more advantageous than in dairy cattle. METHODS: We studied the contribution of genotypes from males and females using a real dataset with genotypes on 15 723 broiler chickens. Genomic evaluations used three training sets that included only males (4648), only females (8100), and both sexes (12 748). Realized accuracies of genomic estimated breeding values (GEBV) were used to evaluate the benefit of including genotypes for different training populations on genomic predictions of young genotyped chickens. RESULTS: Using genotypes on males, the average increase in accuracy of GEBV over pedigree-based EBV for males and females was 12 and 1 percentage points, respectively. Using female genotypes, this increase was 1 and 18 percentage points, respectively. Using genotypes of both sexes increased accuracies by 19 points for males and 20 points for females. For two traits with similar heritabilities and amounts of information, realized accuracies from cross-validation were lower for the trait that was under strong selection. CONCLUSIONS: Overall, genotyping males and females improves predictions of all young genotyped chickens, regardless of sex. Therefore, when males and females both contribute to genetic progress of the population, genotyping both sexes may be the best option. PMID- 26133807 TI - Association between prenatal exposure to polybrominated diphenyl ethers and young children's neurodevelopment in China. AB - The use of polybrominated diphenyl ethers (PBDEs) has been dramatically increasing over the last two decades in China. Animal studies suggest that prenatal exposure to PBDEs may result in neurodevelopmental deficits. Two hundred thirty-two participating mothers were recruited from a prospective birth cohort in rural northern China between September 2010 and February 2012. We analyzed 232 cord blood specimens for selected PBDE congeners and examined their association with children's developmental quotients (DQs) at 12 (n=192) and 24 (n=149) months of age based on the Gesell Developmental Schedules (motor, adaptive, language, and social domains). There were no substantial differences by demographic characteristics among the three time points: baseline, 12 and 24 months of age. Median cord blood levels of PBDE congeners 47, 99, 100, and 153 were 3.71, 6.70, 2.63, and 2.19 ng/g lipid, respectively. At 12 months of age, neither the individual nor total (the sum of BDEs 47, 99, 100, and 153) congener levels were associated with any of the four domain DQs. However, at 24 months of age, a 10 fold increase in BDE-99 levels was associated with a 2.16-point decrease [95% confidence interval (CI): -4.52, -0.20] in language domain DQs and a 10-fold increase in BDE-47 levels was associated with a 1.89-point decrease (95% CI: 3.75, -0.03) in social domain DQs. Prenatal exposure to PBDEs was associated with lower DQs in young children. The results contribute to the growing evidence that PBDEs could act as developmental neurotoxicants,and the findings have implications for children's environmental health in China. PMID- 26133808 TI - Assessing responses of cardiovascular mortality to particulate matter air pollution for pre-, during- and post-2008 Olympics periods. AB - BACKGROUND: The link between particulate air pollution and cardiovascular (CVD) mortality has been investigated. However, there is little direct evidence that reduction measures which decrease particulate air pollution would lead to a reduction in CVD mortality. OBJECTIVES: In Beijing, China, air quality improvement strategies were developed and actions were taken before and during the 2008 Olympic and Paralympic Games. Taking advantage of this opportunity, the aim of the study was to assess the effects of changes in particulate air pollution before (May 20-July 20, 2008), during (August 1-September 20, 2008) and after (October 1-December 1, 2008) the Olympics period. METHODS: Concentrations of air pollution, meteorology and CVD death counts were obtained from official networks and monitoring sites located on the Peking University campus. Air pollution effects with lags of 0-4 days as well as of the 5-day average on cause specific CVD mortality were investigated for the complete study period (May 20 December 1, 2008) using Quasi-Poisson regression models. Different gender and age subgroups were taken into account. Additionally, effect modification by air mass origin was investigated. In a second step, air pollution effects were estimated for the three specific periods by including an interaction term in the models. RESULTS: We observed large concentration decreases in all measured air pollutants during the unique pollution intervention for the Beijing 2008 Olympics. For the whole period, adverse effects of particulate air pollution were observed on CVD mortality with a 1-day delay as well as for the 5-day average exposure, e.g. an 8.8% (95%CI: 2.7-15.2%) increase in CVD mortality with an interquartile range increase in ultrafine particles. The effects were more pronounced in females, the elderly and for cerebrovascular deaths, but not modified by air mass origin. The specific sub-period analysis results suggested that the risks of CVD mortality were lowest during the Olympic Games where strongest reduction measures have been applied. CONCLUSIONS: The results indicated that the reduction of air pollution due to air quality control measures led to a decreased risk of CVD mortality in Beijing. Our findings provide new insight into efforts to reduce ambient air pollution. PMID- 26133810 TI - A proposal for a self removal suture (DZ suture) in dermatologic surgery. PMID- 26133809 TI - Perinatal exposure to chlordecone and infant growth. AB - BACKGROUND: The intensive use of chlordecone (an organochlorine insecticide) in the French West Indies until 1993 resulted in a long-term soil and water contamination. Chlordecone has known hormonal properties and exposure through contaminated food during critical periods of development (gestation and early infancy) may affect growth. OBJECTIVES: We aimed to assess the impact of prenatal and postnatal exposure to chlordecone on the growth of children from the TIMOUN mother-child cohort. METHODS: Chlordecone was determined in cord plasma at birth (N=222) and in breast milk samples (at 3 months). Dietary chlordecone intake was estimated at 7 and 18 months, with food-frequency questionnaires and food specific contamination data. Anthropometric measurements were taken at the 3-, 7- and 18-month visits and measurements reported in the infants' health records were noted. Structured Jenss-Bayley growth models were fitted to individual height and weight growth trajectories. The impact of exposure on growth curve parameters was estimated directly with adjusted mixed non-linear models. Weight, height and body mass index (BMI), and instantaneous height and weight growth velocities at specific ages were also analyzed relative to exposure. RESULTS: Chlordecone in cord blood was associated with a higher BMI in boys at 3 months, due to greater weight and lower height, and in girls at 8 and 18 months, mostly due to lower height. Postnatal exposure was associated with lower height, weight and BMI at 3, 8 and 18 months, particularly in girls. CONCLUSION: Chlordecone exposure may affect growth trajectories in children aged 0 to 18 months. PMID- 26133812 TI - Borderline Personality Disorder in the perinatal period: early infant and maternal outcomes. AB - OBJECTIVE: This study examines pregnancy and early infant outcomes of pregnant women with a clinical diagnosis of Borderline Personality Disorder presenting for obstetric services to a major metropolitan maternity hospital in Victoria, Australia. METHOD: A retrospective case review of pregnancy and early infant outcomes on 42 women who had been diagnosed with Borderline Personality Disorder via psychiatric assessment using DSM-IV-R criteria was undertaken. Outcomes were compared with a control group of 14,313 consisting of women and infants of non affected women from the same hospital over the same period of time. RESULTS: Women presenting for obstetric services with a clinical diagnosis of Borderline Personality Disorder experienced considerable psychosocial impairment. They anticipated birth as traumatic and frequently requested early delivery. High comorbidity with substance abuse was found and high rates of referral to child protective services. Mothers with Borderline Personality Disorder were significantly more likely to have negative birth outcomes such as lowered Apgar scores, prematurity and special care nursery referral when compared with controls. CONCLUSIONS: These findings offer preliminary evidence to be considered by clinicians in developing treatments and services for the perinatal care of women with Borderline Personality Disorder and their infants. Further research is required in order to develop evidence informed clinical guidelines for the management of women with Borderline Personality Disorder and their infants. PMID- 26133813 TI - Gut feelings 2. Mind, mood and gut in inflammatory bowel disease: approaches to psychiatric care. AB - OBJECTIVES: The authors aim to provide a clinically-focused summary of psychiatric complications of inflammatory bowel disease (IBD), and give treatment recommendations.A narrative review of literature drawn from PubMed and Medline. CONCLUSIONS: IBD is a chronic, debilitating and potentially body integrity altering condition with significant morbidity and a slight increase in mortality. Co-morbidity with anxiety and depression is common. Onset in the younger years can disturb development. Psychotherapy may be most useful for addressing fatigue, pain and assisting with coping. There is a lack of evidence to guide treatment of depression in this population. PMID- 26133811 TI - Long-term adjunctive lacosamide treatment in patients with partial-onset seizures. AB - OBJECTIVE: To evaluate long-term (up to 5.5 years) safety, seizure reduction, and maintenance of efficacy of the antiepileptic drug (AED) lacosamide as adjunctive treatment in an open-label extension trial (SP774; ClinicalTrials.gov: NCT00515619). METHODS: Three hundred and seventy-six adults with partial-onset seizures taking 1-3 AEDs enrolled following completion of a double-blind trial of adjunctive lacosamide. During open-label treatment, dosage of lacosamide (100-800 mg/day) and/or concomitant AEDs could be adjusted to optimize tolerability and seizure control. RESULTS: Kaplan-Meier estimates of patient retention were 74.5% at 12 months, 52.9% at 36 months, and 40.6% at 60 months; median open-label treatment duration was 1183 days (~3.2 years). The most frequently reported treatment-emergent adverse events were dizziness (24.2%), headache (14.4%), diplopia (13.8%), and nasopharyngitis (13.8%); 9.0% of patients discontinued due to adverse events, most commonly dizziness (1.3%). Median percent reduction in 28 day seizure frequency from baseline of the double-blind trial was 49.9% overall, 55.4% for 1-year completers, and 62.3% for 3-year completers. Overall, 50.0% of patients were considered >=50% responders (achieved >=50% reduction in 28-day seizure frequency); 55.9% of 1-year completers and 63.0% of 3-year completers were >=50% responders. CONCLUSION: In eligible patients who entered the open label extension trial, lacosamide was generally well tolerated. For most patients within each yearly completer cohort, seizure reduction was maintained over time. PMID- 26133814 TI - [Efficacy and safety of telbivudine alone and combined with adefovir for the treatment of nucleos(t)ide-naive chronic hepatitis B in patients with high-level hepatitis B virus load]. AB - OBJECTIVE: To compare the efficacy of telbivudine monotherapy and telbivudine combination therapy with adefovir in patients with nucleos(t)ide-naive chronic hepatitis B, high-level hepatitis B virus (HBV) load and hepatitis B e antigen (HBeAg)-positivity, and to explore the relationship between treatment regimen adherence and treatment outcomes. METODS: A retrospective study was performed with 123 HBeAg-positive, high-level viral load (HBV DNA>=10(7) copies/ml), nucleos(t)ide-naive chronic hepatitis B patients. Fifty-three of the patients received combination therapy with telbivudine and adefovir dipivoxil,while 70 patients received the telbivudine monotherapy. All patients were tested for rates of conversion to HBV DNA-negative status,alanine aminotransferase (ALT) normalization, HBeAg seroconversion, drug resistance, and side effects at treatment weeks 12, 24, and 48. Treatment regimen adherence was assessed through self-reporting, and interviews were used to explore the relationships to treatment outcomes. The chisquare test, t test and Fisher's exact test were used for statistical analyses. RESULTS: The rates of HBV DNA negative conversion in the combination group at treatment weeks 12, 24 and 48 were 62.3% (33/53), 88.7% (47/53) and 94.3% (50/53) and were significantly different from those in the monotherapy group at weeks 12 and 24.The rates of ALT normalization were significantly different between the two groups at treatment week 12 (94.3% vs. 77.1%). The rate of HBeAg seroconversion in the combination group at treatment week 48 was 39.6%, and significantly different than that of the monotherapy group. The rates of drug-resistance in the combination and monotherapy groups at treatment week 48 were 3.8% and 11.4%, and the proportion of non-adherence to the treatment regimen was 53.3%, which significantly affected treatment outcome. No side effects occurred in either treatment group. CONCLUSION: Telbivudine combination treatment with adefovir was more effective than telbivudine monotherapy and elicited a low drug resistance rate in nucleos(t)idenaive chronic hepatitis B patients with high-level HBV load and HBeAg-positivity. Adherence to the therapy regimen was a key factor influencing treatment outcomes. PMID- 26133815 TI - [Relationship between hepatitis B surface antigen, HBV DNA quantity and liver fibrosis severity]. AB - OBJECTIVE: To explore the correlation between serum hepatitis B surface antigen (HBsAg) level and hepatic tissue pathological staging in patients with chronic hepatitis B (CHB). METHODS: Clinical data was collected from our hospital's records for 302 CHB patients with HBsAg-positive status for more than 6 months and who had undergone hepatic biopsy. The HBsAg level,HBV DNA level and other clinical data were measured using commercial diagnostic assays. Liver histology was scored using the GS staging system. Correlation between serum HBsAg quantity, HBV DNA quantity, stage of inflammation and degree of fibrosis was assessed statistically. RESULTS: The correlation of serum HBsAg level and HBV DNA level was notable. The serum HBsAg level was a variable affecting hepatic tissue pathological stage significantly. Serum HBsAg level appeared to be a highly specific and sensitive diagnostic marker of hepatic fibrosis. As the severity of liver fibrosis increased, the quantitative levels of platelet (PLT), HBsAg and HBV DNA gradually decreased, and the APRI index gradually increased; there were significant differences between the groups (all P<0.001). Serum HBsAg and HBV DNA levels in patients with hepatitis B e antigen-positive (HBeAg(+)) status showed strong correlation (r=0.721, P<0.0001) by Spearman analysis. HBeAg(+) patients with moderate to severe fibrosis (S2-4) exhibited significantly lower serum HBsAg and HBV DNA levels compared with patients with no or mild fibrosis (S0-1; t=5.475 and 4.826, P<0.001). ROC analysis suggested that a serum HBsAg cutoff of 4.46 log 10 IU/mL (28 800 IU/mL) would provide a theoretical sensitivity of 76.3%, with theoretical specificity of 70.5% in HBeAg(+) CHB patients. A serum HBV DNA cutoff of 7.13 log 10 IU/mL (1.35*10(7) copies/mL) would provide a theoretical sensitivity of 71.1%, with theoretical specificity of 73.4% in HBeAg(+) CHB patients. Logistic regression analysis showed that the level of HBsAg was an independent prognostic factor of moderate to severe liver fibrosis, with alanine aminotransferase, aspartate aminotransferase, HBsAg, HBV DNA and PLT (P<0.001). CONCLUSION: HBsAg and HBV DNA levels decrease gradually along with aggravation of liver fibrosis. The cutoff values of 28800 IU/mL for HBsAg and 1.35*10(7) copies/mL ofHBV DNA provide higher specificity and sensitivity for predicting the degree of liver fibrosis in HBeAg-positive CHB patients, and the former is an independent predictor of severe liver fibrosis. PMID- 26133816 TI - [Safety and clinical efficacy of TIPS with various stents for treatment of cirrhosis with esophageal gastric varices bleeding]. AB - OBJECTIVE: To assess the safety and clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with various stents for treating patients with cirrhosis and esophageal gastric varices bleeding. METHODS: One hundred and five patients were stratified according to stent type: bare stent group, covered stent-grafts group, combined stents group. Rates of success, shunt insufficiency, rebleeding, patient survival, and major complications were observed. The shunt insufficiency rate, rebleeding rate, and survival rate were calculated by the life tables method, the Kaplan-Meier analytical curve, and the log-rank test; a p value less than 0.05 was considered statistically significant. RESULTS: The overall success rate of all TIPS for treating the esophageal gastric varices bleeding was 100%. The overall shunt insufficiency rates at 6-, 12-and 24-months post-TIPS were 8%, 9% and 16%, rebleeding rates were 2%, 6% and 17%, and survival rates were 100%, 97% and 94%. The shunt insufficiency rate was 26% in the bare stent group, 14% in the covered stent-grafis group, and 5% in the combined stents group (x2=1.00, P=0.61). The rebleeding rate was 33% in the bare stent group, 7% in the covered stent-grafts group, and 3%in the combined stents group (x2=1.69, P=0.43). The survival rate was 92% in the bare stent group, 93% in the covered stent-grafts group, and 100% in the combined stents group (x2=1.91, P=0.39). The shunt insufficiency rates were higher in patients with splenectomy than in those without splenectomy (30% vs.14%; x2=4.15, P=0.04). The intraperitoneal hemorrhage rates in the covered stent-grafis group and the combined stents group were significantly lower than that in the bare stent group (0% vs 0% vs 13%; x2=8.88, P=0.01). CONCLUSIONS: TIPS with an 8 mm stent effectively treated and prevented esophageal gastric varices bleeding in patients with cirrhosis. Intraperitoneal hemorrhaging caused by TIPS was significantly decreased in the covered stent grafts group and combined stents group,which represented an improvement in safety of this treatment. However, the influence of covered stent-grafis and combined stents towards the clinical efficacy of TIPS needs further study. PMID- 26133817 TI - [Clinical study on FibroTouch and multi-parameter model for diagnosis of hepatic fibrosis in patients with chronic liver disease]. AB - OBJECTIVE: To explore the clinical application and related factors of FibroTouch in the diagnosis of liver fibrosis in patients with chronic liver disease through comparison of the specificity and sensitivity of FibroTouch and multi-parameter models, and to identify whether FibroTouch is a more accurate and safe method in diagnosis of liver fibrosis and evaluation of the therapeutic effect. METHODS: A total of 190 patients with chronic liver disease were performed liver biopsy and underwent liver stiffness measurement (LSM) using FibroTouch in department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University from January 2014 to February 2015. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were tested by enzymic method with automatic biochemistry analyzer. Blood platelet counts were detected by automatic blood cell analyzer. AST-to-PLT ratio index (APRI) and fibrosis index based on the 4 factor (FIB-4) were calculated. The diagnostic values of FibroTouch, APRI and FIB-4 for liver fibrosis degree were calculated and compared by receiver operating characteristic (ROC) curves. The related factors of LSM were analyzed by Spearman analysis. RESULTS: There was significant correlation between LSM and histological fibrosis (r=0.804, P=0.000). The area under ROC curve of LSM for S(>=2, S>=3 and S=4 was 0.894, 0.938 and 0.961, respectively, which was significantly higher than APRI (0.678, 0.698 and 0.658) and FIB-4 (0.765, 0.785 and 0.775). On Spearman analysis, LSM was positively correlated with age, ALT, AST, TBIL ((>=2*ULN) and the grade of liver inflammation (r=0.309, 0.558, 0.504, 0.492 and 0.532, respectively) but negatively with PLT (r=-0.444), (all P<0.05). CONCLUSIONS: LSM is a convenient and reliable approach for diagnosis of liver fibrosis in patients with chronic liver disease. The sensitivity and specificity of Fibrotouch in diagnosis of hepatic fibrosis is superior to APRI and FIB-4, and age, high level ofALT, AST and TBIL (>=2*ULN) were independent predictors of LSM inaccuracy. PMID- 26133818 TI - [Correlation between polymorphisms in the human leukocyte antigen-DQB1 alleles and hepatitis B with primary hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the correlation between polymorphisms in human leukocyte antigen (HLA)-DQB 1 and primary liver cancer (PLC) with hepatitis B virus (HBV) and to search for susceptibility and resistance genes related to PLC with HBV. METHODS: One hundred and eighteen patients with HBV-related liver cancer were enrolled from the First Hospital of Shanxi Medical University. Patients were stratified by family history of hepatitis B (39 with; 79 without) and HBV DNA positivity (60 positive, >=1*10(3) IU/mL; 58 negative, <1*10(3) IU/mL). The HLA-DQB 1 genotype was determined by PCR and direct nucleotide sequence analysis genotyping. Allele frequencies were calculated by the direct counting method. Betweengroup comparisons were carried out with the Chi-square test or Mann-Whitney U test. RESULTS: The allele frequencies of HLA-DQBl*0202 and HLA-DQBl*0301 were significantly higher in patients with hepatocellular carcinoma (HCC) than the control group (1 1.8% and 29.3% vs. 7.6% and 21.1%; U=2.43 and 3.09, P<0.05, RR=1.581 and 1.477). The allele frequencies of HLA-DQB1*0202 and HLADQB 1*0301 were significantly higher in patients with HCC and familial history of hepatitis B than in the normal population (14.1% and 29.5% vs. 7.6% and 21.1%; U=3.76 and 3.16, P less than 0.05, RR=1.928 and 1.495). The allele frequency of HLA-DQB 1*0301 was significantly higher in the HBV DNA positive group than in the HBV DNA negative group (35.0% vs. 23.3%; x2=5.543, P less than 0.05, RR=1.775), while the frequency of HLA-DQB1*0302 was significantly lower in the HBV DNA positive group than in the HBV DNA negative group (10.9% vs. 14.7%; x2=4.604, P<0.05, RR=0.229). CONCLUSIONS: The HLA-DQB 1 *0202 and HLA-DQB 1*0301 alleles may represent susceptibility for PLC with hepatitis B as well as for familial hepatitis B liver cancer. The HLA-DQB 1*0301 allele may support replication of HBV DNA, facilitating progression to liver cancer. The HLA-DQB1*0302 allele may inhibit replication of HBV DNA and reduce the incidence of liver cancer. PMID- 26133819 TI - [Meta-analysis of risk factors of gastroesophageal varices rebleeding after therapeutic endoscopy]. AB - OBJECTIVE: To investigate the risk factors of gastroesophageal varices rebleeding after therapeutic endoscopy. METHODS: Medline,EMBASE and the China Biology Medicine Database were searched for literature published between January 2000 to May 2013 on topics related to risk factors of gastroesophageal varices rebleeding after therapeutic endoscopy. Data from each study that meet the requirements for analysis were extracted and subjected to meta-analysis. RESULTS: Sixteen studies were collected for use in this meta-analysis. The odds ratio (OR) value of portal vein embolus was 7.88 (P<0.00001). The OR value of beta-blockers or nitrate medications was 0.53 (P=0.0008). The standardized mean difference (SMD) value of number of ligation points was 0.94 (P<0.01). The SMD value of albumin in the subgroup with follow-up time of less than or equal to 14 days was-0.89 (P<0.00001), while the SMD value of prothrombin time in the subgroup with follow up time of less than or equal to 14 days was 1.78 (P<0.00001). CONCLUSIONS: Portal vein embolus, hepatocellular carcinoma, diameter of the portal vein, Child Pugh classification C, moderate/excessive ascites, prothrombin time, and number of ligation points were risk factors of gastroesophageal varices early rebleeding after therapeutic endoscopy. Portal vein embolus, hepatocellular carcinoma, and diameter of the portal vein were risk factors of gastroesophageal varices long term rebleeding after therapeutic endoscopy. Beta blockers or nitrate medications were protective factors of gastroesophageal varices rebleeding after therapeutic endoscopy. PMID- 26133820 TI - [Effects of telmisartan on resistin expression in a rat model of nonalcoholic steatohepatitis and insulin resistance]. AB - OBJECTIVE: To investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system. METHODS: Forty-five male Sprague Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses. RESULTS: Compared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (P<0.01). The levels of serum resistin, and of resistin protein and mRNA in liver, were significantly higher in the MC group than in the NC group of rats (all P less than 0.01). The body weight of rats in the TP group was significantly lower than those in the MC group (P<0.05). The levels of serrn resistin, resistin protein and mRNA in the liver, and insulin resistance were significantly lower in the TP group than in the MC group of rats (all P<0.01). The PP group did not show significant differences in any of these measures, except for loss of body weight (P<0.05). CONCLUSION: Telmisartan elicits preventive and protective effects in a NASH rat model.Telmisartan may improve insulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA. PMID- 26133821 TI - [Effects of 4-phenylbutyric acid on carbon tetrachloride-induced acute liver injury in mice]. AB - OBJECTIVE: To explore the effects and the molecular mechanisms of 4-phenylbutyric acid (PBA) on carbon tetraehloride (CCl4)-induced acute liver injury in mice. METHODS: Sixty adult, healthy, male ICR mice were divided equally into the control group, PBA group, CCl4 12 h group, CCl4 24 h group, CCl4 48 h group, CCl4 72 h group, PBA+CCl4 12 h group, PBA+CCl4 24 h group, PBA+CCl4 48 h group, and PBA+CCl4 72 h group. The CCl4 groups and the PBA+CCl4 groups were intraperitoneally (i.p.) injected with CCl4 (300 mL/kg). In the PBA+CCl4 groups, the mice were i.p. injected with PBA (400 mg/kg). All mice were sacrificed to collect blood and liver specimens at different time points after the CCl4 treatment. Serum alanine aminotransferase (ALT) was detected. Histological examination was performed using hematoxylin-eosin staining and light microscopy, and apoptosis was detected using terminal transferase dUTP nick end labeling. The hepatic distribution of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. The hepatic protein expression of glucose-regulated protein (GRP78), C/EBP homologousprotein (CHOP), phosphorylated c-Jun N-terminal kinases (p-JNK), phosphorylated eukaryotic initiation factor 2a subunit (p-eIF2a), phosphorylated serine threonine kinase (p-akt), and nuclear factor-kappa B p65 (NF-kappa Bp65) were determined by western blot. RESULTS: The serum ALT level in the PBA+CCl4 groups was reduced as compared with that in the CCl4 groups at the various time points examined.The liver-to-body weight ratio of two groups showed a significant difference only at the 48 h time point (P<0.01). PBA reduced the degree of hepatic necrosis and apoptosis caused by CCl4, and reduced the expression of hepatic GRP78 and other endoplasmic reticulum stress-related proteins (P<0.01). The protein levels of p-akt, NF-kappa Bp65 and PCNA was significantly decreased in the PBA+CCl4 groups (P<0.01). CONCLUSION: The endoplasmic reticulum stress inhibitor PBA alleviated acute hepatic necrosis and apoptosis but restrained hepatic proliferation. PMID- 26133822 TI - Photoluminescence excitation measurements using pressure-tuned laser diodes. AB - Pressure-tuned laser diodes in external cavity were used as tunable sources for photoluminescence excitation (PLE) spectroscopy. The method was demonstrated in the 720 nm-1070 nm spectral range using a few commercial laser diodes. The samples for PLE measurements were quantum-well structures grown on GaAs and on InP. The method is superior to standard PLE measurements using titanium sapphire laser because it can be extended to any spectral range where anti-reflection coated laser diodes are available. PMID- 26133823 TI - A photoelastic measurement system for residual stress analysis in scintillating crystals by conoscopic imaging. AB - The assessment of the stress state of scintillating crystals is an important issue for producers as well as users of such materials, because residual stress may arise during growth process. In this paper, a measurement system, based on the use of a photoelastic, conoscopic optical setup, is proposed for the assessment of stress state in scintillating crystals. Local stress values can be measured on the crystal in order to observe their spatial distribution. With the proposed system, it is possible to vary the dimensions of the inspected measurement volume. It has been validated with reference to a known stress state induced in a birefringent crystal sample and it has been tested for the case of loaded and unloaded samples, showing sub-millimetric spatial resolution and stress uncertainty <=0.25 MPa. The proposed measurement system is a valid method for the inspection of scintillating crystals required by producers and users of such materials. PMID- 26133824 TI - Single-pulse picking at kHz repetition rates using a Ge plasma switch at the free electron laser FELBE. AB - We demonstrate a system for picking of mid-infrared and terahertz (THz) radiation pulses from the free-electron laser (FEL) FELBE operating at a repetition rate of 13 MHz. Single pulses are reflected by a dense electron-hole plasma in a Ge slab that is photoexcited by amplified near-infrared (NIR) laser systems operating at repetition rates of 1 kHz and 100 kHz, respectively. The peak intensity of picked pulses is up to 400 times larger than the peak intensity of residual pulses. The required NIR fluence for picking pulses at wavelengths in the range from 5 MUm to 30 MUm is discussed. In addition, we show that the reflectivity of the plasma decays on a time scale from 100 ps to 1 ns dependent on the wavelengths of the FEL and the NIR laser. The plasma switch enables experiments with the FEL that require high peak power but lower average power. Furthermore, the system is well suited to investigate processes with decay times in the MUs to ms regime, i.e., much longer than the 77 ns long pulse repetition period of FELBE. PMID- 26133825 TI - An atomic magnetometer with autonomous frequency stabilization and large dynamic range. AB - The operation of a highly sensitive atomic magnetometer using elliptically polarized resonant light is demonstrated. It is based on measurement of zero magnetic field resonance in degenerate two level systems using polarimetric detection. The transmitted light through the polarimeter is used for laser frequency stabilization, whereas reflected light is used for magnetic field measurement. Thus, the experimental geometry allows autonomous frequency stabilization of the laser frequency leading to compact operation of the overall device and has a preliminary sensitivity of <10 pT/Hz(1/2) @ 1 Hz. Additionally, the dynamic range of the device is improved by feedback controlling the bias magnetic field without compromising on its sensitivity. PMID- 26133826 TI - The generation of 68 Gbps quantum random number by measuring laser phase fluctuations. AB - The speed of a quantum random number generator is essential for practical applications, such as high-speed quantum key distribution systems. Here, we push the speed of a quantum random number generator to 68 Gbps by operating a laser around its threshold level. To achieve the rate, not only high-speed photodetector and high sampling rate are needed but also a very stable interferometer is required. A practical interferometer with active feedback instead of common temperature control is developed to meet the requirement of stability. Phase fluctuations of the laser are measured by the interferometer with a photodetector and then digitalized to raw random numbers with a rate of 80 Gbps. The min-entropy of the raw data is evaluated by modeling the system and is used to quantify the quantum randomness of the raw data. The bias of the raw data caused by other signals, such as classical and detection noises, can be removed by Toeplitz-matrix hashing randomness extraction. The final random numbers can pass through the standard randomness tests. Our demonstration shows that high speed quantum random number generators are ready for practical usage. PMID- 26133827 TI - The design of double electrostatic-lens optics for resonance enhanced multiphoton ionization and photoelectron imaging experiments. AB - Compared to single ion/electron-optics for velocity-map imaging, a double focusing lens assembly designed not only allows for mapping velocity imaging of photoelectrons but also allows for investigating the vibrational structure of the intermediate states of neutral species in resonance enhanced multiphoton ionization (REMPI) spectra. In this presentation, in order to record REMPI and photoelectron spectra separately, we have constructed a compact photoelectron velocity-map imaging (VMI) apparatus combined with an opposite linear Wiley Mclaren time-of-flight mass spectrometer (TOFMS). A mass resolution (m/Deltam) of ~1300 for TOFMS and electron energy resolution (DeltaE/E) of 2.4% for VMI have been achieved upon three-photon ionization of Xe atom at 258.00 nm laser wavelength. As a benchmark, in combination of one-color (1 + 1) REMPI and photoelectron imaging of benzene via 6(1) and 6(1)1(1) vibronic levels in the S1 state, the vibrational structures of the cation and photoelectron angular anisotropy are unraveled. In addition, two-color (1 + 1') REMPI and photoelectron imaging of aniline was used to complete the accurate measurement of ionization potential (62,271 +/- 3 cm(-1)). The results suggest that the apparatus is a powerful tool for studying photoionization dynamics in the photoelectron imaging using vibrational-state selected excitation to the intermediate states of neutrals based on REMPI technique. PMID- 26133828 TI - Characterization of a new electrostatic storage ring for photofragmentation experiments. AB - We describe the design of and the first commissioning experiments with a newly constructed electrostatic storage ring named SAPHIRA (Storage Ring in Aarhus for PHoton-Ion Reaction Analysis). With an intense beam of Cu(-) at 4 keV, the storage ring is characterized in terms of the stored ion beam decay rate, the longitudinal spreading of an injected ion bunch, as well as the direct measurements of the transverse spatial distributions under different conditions of storage. The ion storage stability in SAPHIRA was investigated systematically in a selected region of its electrical configuration space. PMID- 26133829 TI - Figure correction of a metallic ellipsoidal neutron focusing mirror. AB - An increasing number of neutron focusing mirrors is being adopted in neutron scattering experiments in order to provide high fluxes at sample positions, reduce measurement time, and/or increase statistical reliability. To realize a small focusing spot and high beam intensity, mirrors with both high form accuracy and low surface roughness are required. To achieve this, we propose a new figure correction technique to fabricate a two-dimensional neutron focusing mirror made with electroless nickel-phosphorus (NiP) by effectively combining ultraprecision shaper cutting and fine polishing. An arc envelope shaper cutting method is introduced to generate high form accuracy, while a fine polishing method, in which the material is removed effectively without losing profile accuracy, is developed to reduce the surface roughness of the mirror. High form accuracy in the minor-axis and the major-axis is obtained through tool profile error compensation and corrective polishing, respectively, and low surface roughness is acquired under a low polishing load. As a result, an ellipsoidal neutron focusing mirror is successfully fabricated with high form accuracy of 0.5 MUm peak-to valley and low surface roughness of 0.2 nm root-mean-square. PMID- 26133830 TI - Photoluminescence-based detection of particle contamination on extreme ultraviolet reticles. AB - Here, we propose a comparison-free inspection technique to detect particle contamination on the reticle of extreme ultraviolet (EUV) lithography systems, based on the photoluminescence spectral characteristics of the contaminant particles and their elemental composition. We have analyzed the spectra from different particles found on reticles in EUV lithographic systems and have determined the minimum detectable particle size: 25 nm for organic particles and 100 nm for Al particles. Stainless steel coatings (50 nm thick and 50 * 50 MUm(2) in area) exhibit detectable photoluminescence, and the estimated minimum detectable particle is 2 MUm. PMID- 26133831 TI - A Ku band pulsed electron paramagnetic resonance spectrometer using an arbitrary waveform generator for quantum control experiments at millikelvin temperatures. AB - We present a 17 GHz (Ku band) arbitrary waveform pulsed electron paramagnetic resonance spectrometer for experiments down to millikelvin temperatures. The spectrometer is located at room temperature, while the resonator is placed either in a room temperature magnet or inside a cryogen-free dilution refrigerator; the operating temperature range of the dilution unit is from ca. 10 mK to 8 K. This combination provides the opportunity to perform quantum control experiments on electron spins in the pure-state regime. At 0.6 T, spin echo experiments were carried out using gamma-irradiated quartz glass from 1 K to 12.3 mK. With decreasing temperatures, we observed an increase in spin echo signal intensities due to increasing spin polarizations, in accordance with theoretical predictions. Through experimental data fitting, thermal spin polarization at 100 mK was estimated to be at least 99%, which was almost pure state. Next, to demonstrate the ability to create arbitrary waveform pulses, we generate a shaped pulse by superposing three Gaussian pulses of different frequencies. The resulting pulse was able to selectively and coherently excite three different spin packets simultaneously-a useful ability for analyzing multi-spin system and for controlling a multi-qubit quantum computer. By applying this pulse to the inhomogeneously broadened sample, we obtain three well-resolved excitations at 8 K, 1 K, and 14 mK. PMID- 26133832 TI - Synchronous characterization of semiconductor microcavity laser beam. AB - We report on a high-resolution double-channel imaging method used to synchronously map the intensity- and optical-frequency-distribution of a laser beam in the plane orthogonal to the propagation direction. The synchronous measurement allows us to show that the laser frequency is an inhomogeneous distribution below threshold, but that it becomes homogeneous across the fundamental Gaussian mode above threshold. The beam's tails deviations from the Gaussian shape, however, are accompanied by sizeable fluctuations in the laser wavelength, possibly deriving from manufacturing details and from the influence of spontaneous emission in the very low intensity wings. In addition to the synchronous spatial characterization, a temporal analysis at any given point in the beam cross section is carried out. Using this method, the beam homogeneity and spatial shape, energy density, energy center, and the defects-related spectrum can also be extracted from these high-resolution pictures. PMID- 26133833 TI - Inverse mirror plasma experimental device-A new magnetized linear plasma device with wide operating range. AB - Inverse mirror plasma experimental device has been designed and fabricated for detailed experimental investigation of phase mixing and wave breaking of plasma oscillation/wave. The device produces quiescent magnetized plasma over a wide operating range using multifilamentary source with low filament spacing in cusp geometry along with a flexible transition magnetic field region between the plasma source chamber and the main chamber. Argon plasma has been produced in the device over a wide pressure range from 1.7 * 10(-5) mbar to 9 * 10(-4) mbar, achieving plasma densities in the range of ~10(9) cm(-3)-10(12) cm(-3) and temperatures in the range of ~1.7 eV-5 eV. To fulfill a desired prerequisite of having quiescent plasma (deltan/n <= 1%) for realizing phase mixing of nonlinear plasma oscillation and other wave experiments, a quiescent magnetized plasma is obtained: typical quiescence, deltan/n ~ 0.5% at 10(-4) mbar and B(main) ~ 1 kG. The potential of the multifilamentary plasma source has been experimentally explored using a flexible transition magnetic field and the usual control features of a filament discharge. Probe measurements reveal that the plasma to be axially and radially uniform, an excellent scenario for wave launching and studying its propagating and phase mixing characteristics. PMID- 26133834 TI - A linear radio frequency plasma reactor for potential and current mapping in a magnetized plasma. AB - Langmuir probe measurements in front of high power ion cyclotron resonant frequency antennas are not possible or simply too noisy to be analyzed properly. A linear experiment is a radio frequency (RF) magnetized plasma discharge reactor designed to probe the rectified potential in front of such antennas but at low power level (1 kW) to next improve antenna design and mitigate sheath effects. The maximum magnetic field is 0.1 T, and the RF amplifier can work between 10 kHz and 250 MHz allowing ion cyclotron resonances for argon or helium. The first measurements with no magnetic field are presented here, especially 2D potential maps extracted from the RF compensated probe measurements yield ni ~ 10(15) m(-3) and Te ~ 2 eV for RF power lower than 100 W. Series resonances in the chamber are highlighted and allow to deduce the plasma parameters from a simple equivalent impedance model of the plasma in helium gas. Next studies will be focused on magnetized plasmas and especially magnetized RF sheaths. PMID- 26133835 TI - A fast rise-rate, adjustable-mass-bit gas puff valve for energetic pulsed plasma experiments. AB - A fast rise-rate, variable mass-bit gas puff valve based on the diamagnetic repulsion principle was designed, built, and experimentally characterized. The ability to hold the pressure rise-rate nearly constant while varying the total overall mass bit was achieved via a movable mechanical restrictor that is accessible while the valve is assembled and pressurized. The rise-rates and mass bits were measured via piezoelectric pressure transducers for plenum pressures between 10 and 40 psig and restrictor positions of 0.02-1.33 cm from the bottom of the linear restrictor travel. The mass-bits were found to vary linearly with the restrictor position at a given plenum pressure, while rise-rates varied linearly with plenum pressure but exhibited low variation over the range of possible restrictor positions. The ability to change the operating regime of a pulsed coaxial plasma deflagration accelerator by means of altering the valve parameters is demonstrated. PMID- 26133836 TI - Electric field induced Lyman-alpha emission of a hydrogen beam for electric field measurements. AB - Electric field induced Lyman-alpha emission is a new way of measuring weak electric fields in vacuum and in a plasma. It is based on the emission of Lyman alpha radiation (121.6 nm) by a low-energy metastable H atom beam due to Stark quenching of the 2s level induced by the field. In this paper, we describe the technique in detail. Test measurements have been performed in vacuum between two plates polarized at a controlled voltage. The intensity of emitted radiation, proportional to the square of the field modulus, has been recorded by a lock-in technique, which gives an excellent signal to noise ratio. These measurements provide an in situ calibration that can be used to obtain the absolute value of the electric field. A diagnostic of this type can help to address a long standing challenge in plasma physics, namely, the problem of measuring electric fields without disturbing the equilibrium of the system that is being studied. PMID- 26133837 TI - Neutron yield enhancement in laser-induced deuterium-deuterium fusion using a novel shaped target. AB - Neutron yields have direct correlation with the energy of incident deuterons in experiments of laser deuterated target interaction [Roth et al., Phys. Rev. Lett. 110, 044802 (2013) and Higginson et al., Phys. Plasmas 18, 100703 (2011)], while deuterated plasma density is also an important parameter. Experiments at the Shenguang II laser facility have produced neutrons with energy of 2.45 MeV using d (d, n) He reaction. Deuterated foil target and K-shaped target were employed to study the influence of plasma density on neutron yields. Neutron yield generated by K-shaped target (nearly 10(6)) was two times higher than by foil target because the K-shaped target results in higher density plasma. Interferometry and multi hydro-dynamics simulation confirmed the importance of plasma density for enhancement of neutron yields. PMID- 26133838 TI - Sub-micrometer resolution proximity X-ray microscope with digital image registration. AB - A compact laboratory proximity soft X-ray microscope providing submicrometer spatial resolution and digital image registration is described. The microscope consists of a laser-plasma soft X-ray radiation source, a Schwarzschild objective to illuminate the test sample, and a two-coordinate detector for image registration. Radiation, which passes through the sample under study, generates an absorption image on the front surface of the detector. Optical ceramic YAG:Ce was used to convert the X-rays into visible light. An image was transferred from the scintillator to a charge-coupled device camera with a Mitutoyo Plan Apo series lens. The detector's design allows the use of lenses with numerical apertures of NA = 0.14, 0.28, and 0.55 without changing the dimensions and arrangement of the elements of the device. This design allows one to change the magnification, spatial resolution, and field of view of the X-ray microscope. A spatial resolution better than 0.7 MUm and an energy conversion efficiency of the X-ray radiation with a wavelength of 13.5 nm into visible light collected by the detector of 7.2% were achieved with the largest aperture lens. PMID- 26133839 TI - Automation of a single-DNA molecule stretching device. AB - We automate the manipulation of genomic-length DNA in a nanofluidic device based on real-time analysis of fluorescence images. In our protocol, individual molecules are picked from a microchannel and stretched with pN forces using pressure driven flows. The millimeter-long DNA fragments free flowing in micro- and nanofluidics emit low fluorescence and change shape, thus challenging the image analysis for machine vision. We demonstrate a set of image processing steps that increase the intrinsically low signal-to-noise ratio associated with single molecule fluorescence microscopy. Furthermore, we demonstrate how to estimate the length of molecules by continuous real-time image stitching and how to increase the effective resolution of a pressure controller by pulse width modulation. The sequence of image-processing steps addresses the challenges of genomic-length DNA visualization; however, they should also be general to other applications of fluorescence-based microfluidics. PMID- 26133840 TI - Method of mechanical holding of cantilever chip for tip-scan high-speed atomic force microscope. AB - In tip-scan atomic force microscopy (AFM) that scans a cantilever chip in the three dimensions, the chip body is held on the Z-scanner with a holder. However, this holding is not easy for high-speed (HS) AFM because the holder that should have a small mass has to be able to clamp the cantilever chip firmly without deteriorating the Z-scanner's fast performance, and because repeated exchange of cantilever chips should not damage the Z-scanner. This is one of the reasons that tip-scan HS-AFM has not been established, despite its advantages over sample stage-scan HS-AFM. Here, we present a novel method of cantilever chip holding which meets all conditions required for tip-scan HS-AFM. The superior performance of this novel chip holding mechanism is demonstrated by imaging of the alpha3beta3 subcomplex of F1-ATPase in dynamic action at ~7 frames/s. PMID- 26133841 TI - Novel comparison of microscopy and diffraction techniques on the structure of iron oxide nanoparticle monolayers transferred by Langmuir-Schaefer method. AB - Iron oxide nanoparticles undergo self-assembly into well-ordered monolayer films of macroscopic size at the air-water interface. This self-assembly process is the result of the van der Waals forces between the constituent particles. For roughly spherical particles, this monolayer is a 2D hexagonal close packed lattice. With Grazing Incidence X-Ray Diffraction (GID), one can obtain global statistical information about the film's spacing and correlation length. Herein, we demonstrate that comparable structural information can be obtained by a novel Fourier transform analysis method applied to Scanning Electron Microscopy (SEM) images taken of the film after it has been transferred to a silicon substrate. This consists of using numerical methods to isolate the lattice structure of the monolayer in the SEM image to which a 2D discrete Fourier Transform is applied and the result integrated. This results in Bragg peak information akin to that obtained from GID, whose structure shows the same hexagonal close packed lattice with similar spacing and of greater peak contrast. This analysis technique may prove to be a suitable alternative or compliment to GID for many applications. PMID- 26133842 TI - A versatile x-ray microtomography station for biomedical imaging and materials research. AB - An x-ray microtomography station implemented at the X-ray Applied Crystallography Laboratory of the State University of Campinas is described. The station is based on a propagation based phase contrast imaging setup with a microfocus source and digital x-ray area detectors. Due to its simplicity, this setup is ideal for fast, high resolution imaging and microtomography of small biological specimens and materials research samples. It can also be coupled to gratings to use and develop new techniques as the harmonic spatial coherent imaging, which allow scattering contrast imaging. Details of the experimental setup, equipment, and software integration are described. Test microtomography for setup commissioning and characterization is shown. We conclude that phase contrast enhanced x-ray imaging and microtomography with resolution below 5 MUm voxel size are possible and data sets as wide as 2000 * 2000 * 2000 voxels are obtained with this instrumentation. PMID- 26133843 TI - Microcantilever based distance control between a probe and a surface. AB - We demonstrate a method to control the distance between a custom probe and a sample on a MUm to nm scale. The method relies on the closed-loop feedback on the angular deflection of an in-contact AFM microcantilever. High performance in stability and accuracy is achieved in this method by taking advantage of the small mechanical feedback path between surface and probe. We describe how internal error sources that find their origin in the microcantilever and feedback can be minimized to achieve an accurate and precise control up to 3 nm. In particular, we investigated how hysteresis effects in the feedback caused by friction forces between tip and substrate can be minimized. By applying a short calibration procedure, distance control from contact to several micrometers probe sample distance can be obtained with an absolute nanometer-scale accuracy. The method presented is compatible with any probe that can be fixed on a microcantilever chip and can be easily built into existing AFM systems. PMID- 26133844 TI - Study of in situ adsorption kinetics of polyelectrolytes and liposomes using quartz crystal microbalance: Influence of experimental layout. AB - Quartz Crystal Microbalance (QCM) is a widely used technique to characterize adsorption/desorption phenomena at the solid/liquid interface. However, the obtained adsorption/desorption kinetics curves are often not reproducible and present some noise and long term fluctuations. In this work, the accuracy of a commercial QCM to measure the adsorbed amount of polyelectrolytes and biological molecules was evaluated in terms of experimental QCM configurations with respect to quality, stability, and reproducibility of the measured data. Evaluation consisted in comparing the adsorption kinetics curves of the cationic polyelectrolyte poly(ethyleneimine) and the anionic 1,2-dipalmitoyl-sn-glycero-3 phospho-(1'-rac-glycerol) (sodium salt) liposomes, when setting the quartz crystal surface in stationary horizontal open, stationary horizontal closed, stationary vertical open, continuous vertical closed, and stationary vertical closed measuring configuration. For this last configuration, a new cell was designed and implemented. The analysis of the kinetics curves revealed that horizontal modes are more unstable when subjected to fostering noise due to the mechanical vibrations and lead to resonance frequency shift. This shift is caused by the measurement of non-adsorbed molecules which are deposited on the quartz crystal due to gravity force. The vertical modes proved to be more reproducible and reliable. PMID- 26133845 TI - ALICE-An advanced reflectometer for static and dynamic experiments in magnetism at synchrotron radiation facilities. AB - We report on significant developments of a high vacuum reflectometer (diffractometer) and spectrometer for soft x-ray synchrotron experiments which allows conducting a wide range of static and dynamic experiments. Although the chamber named ALICE was designed for the analysis of magnetic hetero- and nanostructures via resonant magnetic x-ray scattering, the instrument is not limited to this technique. The versatility of the instrument was testified by a series of pilot experiments. Static measurements involve the possibility to use scattering and spectroscopy synchrotron based techniques (photon-in photon-out, photon-in electron-out, and coherent scattering). Dynamic experiments require either laser or magnetic field pulses to excite the spin system followed by x-ray probe in the time domain from nano- to femtosecond delay times. In this temporal range, the demagnetization/remagnetization dynamics and magnetization precession in a number of magnetic materials (metals, alloys, and magnetic multilayers) can be probed in an element specific manner. We demonstrate here the capabilities of the system to host a variety of experiments, featuring ALICE as one of the most versatile and demanded instruments at the Helmholtz Center in Berlin-BESSY II synchrotron center in Berlin, Germany. PMID- 26133846 TI - Electrochemical cell for in situ electrodeposition of magnetic thin films in a superconducting quantum interference device magnetometer. AB - An electrochemical cell is designed and applied for in situ electrodeposition of magnetic thin films in a commercial SQUID magnetometer system. The cell is constructed in such a way that any parasitic contribution of the cell and of the substrate for electrodeposition to the magnetic moment of the deposited film is reduced to a minimum. A remanent minor contribution is readily taken into account by a proper analysis of the detected signal. Thus, a precise determination of the absolute magnetic moment of the electrodeposited magnetic film during its growth and dissolution is achieved. The feasibility of the cell design is demonstrated by performing Co electrodeposition using cyclic voltammetry. For an average Co film thickness of (35.6 +/- 3.0) atomic layers, a magnetic moment per Co atom of (1.75 +/- 0.11) MU(B) was estimated, in good agreement with the literature bulk value. PMID- 26133847 TI - Near-isothermal furnace for in situ and real time X-ray radiography solidification experiments. AB - In this paper, we present a newly developed near-isothermal X-ray transparent furnace for in situ imaging of solidification processes in thin metallic samples. We show that the furnace is ideally suited to study equiaxed microstructure evolution and grain interaction. To observe the growth dynamics of equiaxed dendritic structures, a minimal temperature gradient across the sample is required. A uniform thermal profile inside a circular sample is achieved by positioning the sample in the center of a cylindrical furnace body surrounded by a circular heater arrangement. Performance tests with the hypo-eutectic Al 15wt.%Cu and the near-eutectic Al-33wt.%Cu alloys validate the near-isothermal character of the sample environment. Controlled cooling rates of less than 0.5 K min(-1) up to 10 K min(-1) can be achieved in a temperature range of 720 K-1220 K. Integrated in our rotatable laboratory X-ray facility, X-RISE, the furnace provides a large field of view of 10.5 mm in diameter and a high spatial resolution of ~4 MUm. With the here presented furnace, equiaxed dendrite growth models can be rigorously tested against experiments on metal alloys by, e.g., enabling dendrite growth velocities to be determined as a function of undercooling or solutal fields in front of the growing dendrite to be measured. PMID- 26133848 TI - Single-crystal Brillouin spectroscopy with CO2 laser heating and variable q. AB - We describe a Brillouin spectroscopy system integrated with CO2 laser-heating and Raman spectroscopic capabilities. Temperature is determined by measurements of the grey-body thermal radiation emitted by the hot sample, with the system response calibrated relative to a standard tungsten ribbon lamp. High-pressure laser-heating Brillouin scattering measurements of acoustic velocities on liquid water and ice compressed in a diamond-anvil cell were performed at temperatures up to 2500 +/- 150 K at high pressure. Single-crystal laser-heating Brillouin measurements were made on the (111) plane of San Carlos olivine at ~13 GPa, 1300 +/- 200 K. The pressure as measured by ruby fluorescence is shown to be within +/ 0.5 GPa of the pressure on the olivine sample during laser heating when KCl and KBr are used as pressure-transmitting media. In addition, the system is designed for continuously variable scattering angles from forward scattering (near 0 degrees scattering angle) up to near back scattering (~141 degrees ). This novel setup allows us to probe a wide range of wave vectors q for investigation of phonon dispersion on, for example, crystals with large unit cells (on the scale of hundreds of nm). PMID- 26133849 TI - Rotating disk electrode system for elevated pressures and temperatures. AB - We describe the development and test of an elevated pressure and temperature rotating disk electrode (RDE) system that allows measurements under well-defined mass transport conditions. As demonstrated for the oxygen reduction reaction on polycrystalline platinum (Pt) in 0.5M H2SO4, the setup can easily be operated in a pressure range of 1-101 bar oxygen, and temperature of 140 degrees C. Under such conditions, diffusion limited current densities increase by almost two orders of magnitude as compared to conventional RDE setups allowing, for example, fuel cell catalyst studies under more realistic conditions. Levich plots demonstrate that the mass transport is indeed well-defined, i.e., at low electrode potentials, the measured current densities are fully diffusion controlled, while at higher potentials, a mixed kinetic-diffusion controlled regime is observed. Therefore, the setup opens up a new field for RDE investigations under temperature and current density conditions relevant for low and high temperature proton exchange membrane fuel cells. PMID- 26133850 TI - An improved sensor for electrochemical microcalorimetry, based on lithiumtantalate. AB - We have developed a pyroelectric sensor for electrochemical microcalorimetry, based on LiTaO3, which provides unprecedented sensitivity for the detection of electrochemically induced heat effects. Deterioration of the heat signal by electrostriction effects on the electrode surface is suppressed by a multilayered construction, where an intermediate sapphire sheet dampens mechanical deformations. Thus, well textured thin metal films become viable candidates as electrodes. We demonstrate the sensor performance for Cu underpotential deposition on (111)-textured Au films on sapphire. The sensor signal compares well with a purely thermal signal induced by heating with laser pulses. The high sensitivity of the sensor is demonstrated by measuring heat effects upon double layer charging in perchloric acid, i.e., in the absence of electrochemical charge or ion-transfer reactions. PMID- 26133851 TI - A combined electrochemical and optical trapping platform for measuring single cell respiration rates at electrode interfaces. AB - Metal-reducing bacteria gain energy by extracellular electron transfer to external solids, such as naturally abundant minerals, which substitute for oxygen or the other common soluble electron acceptors of respiration. This process is one of the earliest forms of respiration on earth and has significant environmental and technological implications. By performing electron transfer to electrodes instead of minerals, these microbes can be used as biocatalysts for conversion of diverse chemical fuels to electricity. Understanding such a complex biotic-abiotic interaction necessitates the development of tools capable of probing extracellular electron transfer down to the level of single cells. Here, we describe an experimental platform for single cell respiration measurements. The design integrates an infrared optical trap, perfusion chamber, and lithographically fabricated electrochemical chips containing potentiostatically controlled transparent indium tin oxide microelectrodes. Individual bacteria are manipulated using the optical trap and placed on the microelectrodes, which are biased at a suitable oxidizing potential in the absence of any chemical electron acceptor. The potentiostat is used to detect the respiration current correlated with cell-electrode contact. We demonstrate the system with single cell measurements of the dissimilatory-metal reducing bacterium Shewanella oneidensis MR-1, which resulted in respiration currents ranging from 15 fA to 100 fA per cell under our measurement conditions. Mutants lacking the outer-membrane cytochromes necessary for extracellular respiration did not result in any measurable current output upon contact. In addition to the application for extracellular electron transfer studies, the ability to electronically measure cell-specific respiration rates may provide answers for a variety of fundamental microbial physiology questions. PMID- 26133852 TI - A radio-frequency coil for the microwave characterization of vortex dynamics in thin film superconductors. AB - A radio-frequency coil for the experimental investigation of the magnetic properties of thin superconducting films under microwave fields at different values of temperature and dc magnetic field has been developed. The system has been used for low-temperature microwave frequency-dependent magnetization measurements in a Pb thin film with an engineered periodical antidot array. The characteristic frequencies and the electric and magnetic fields of the resonant system formed by a multi-turn coil with a sample loaded in its core are estimated using the helical approach. A good agreement of the calculated values with those recorded in swept-frequency spectra is obtained. The relation between the characteristics of the resonant structure and the frequency-driven magnetic response of the sample at different nominal microwave powers documents the capability and sensitivity of the layout. PMID- 26133853 TI - Development of an improved H-bridge cascaded static synchronous compensator in power system. AB - This paper presents a new configuration of H-bridge cascaded static synchronous compensator (STATCOM) based on auto disturbance rejection control and modulation wave shifting control intended for installation in industrial and utility power distribution systems. It proposes an improved controller that devotes itself not only to satisfying the requirement of dynamic reactive power compensation but also to achieving the balance of DC capacitor voltage. The new configuration is prominent in having no restriction on the number of power module. Simulation results show the proposed controller exhibits better performance in terms of response time and transient stability compared with the proportion integration controller. Two actual H-bridge cascaded STATCOMs are constructed at 10 kV, 2 MVA and 380 V, 6.5 kVA, respectively, and a series of verifications test are executed in 380 V, 6.5 kVA STATCOM experimental system. The experiment results further prove that H-bridge cascaded STATCOM with the proposed controller has excellent dynamic performance and strong robustness. PMID- 26133854 TI - Design and microwave test of an ultrawideband input/output structure for sheet beam travelling wave tubes. AB - Broadband operation is of great importance for the applications of travelling wave tubes such as high-data communication and wideband radar. An input/output (I/O) structure operating with broadband property plays a significant role to achieve these applications. In this paper, a Y-type branch waveguide (YTBW) coupler and its improvements are proposed and utilized to construct an extremely wideband I/O structure to ensure the broadband operation for sheet beam travelling wave tubes (SB-TWTs). Cascaded reflection resonators are utilized to improve the isolation characteristic and transmission efficiency. Furthermore, to minimize the reflectivity of the port connected with the RF circuit, wave absorbing material (WAM) is loaded in the resonator. Simulation results for the YTBW loaded with WAM predict an excellent performance with a 50.2% relative bandwidth for port reflectivity under -15 dB, transmission up to -1.5 dB, and meanwhile isolation under -20 dB. In addition, the coupler has a relatively compact configuration and the beam tunnel can be widened, which is beneficial for the propagation of the electrons. A Q-band YTBW loaded with two reflection resonators is fabricated and microwave tested. Vector network analyzer (VNA) measured results have an excellent agreement with our simulation, which verify our theoretical analysis and simulation calculation. PMID- 26133855 TI - Single spin optically detected magnetic resonance with 60-90 GHz (E-band) microwave resonators. AB - Magnetic resonance with ensembles of electron spins is commonly performed around 10 GHz, but also at frequencies above 240 GHz and in corresponding magnetic fields of over 9 T. However, experiments with single electron and nuclear spins so far only reach into frequency ranges of several 10 GHz, where existing coplanar waveguide structures for microwave (MW) delivery are compatible with single spin readout techniques (e.g., electrical or optical readout). Here, we explore the frequency range up to 90 GHz, with magnetic fields of up to ~3 T for single spin magnetic resonance in conjunction with optical spin readout. To this end, we develop MW resonators with optical single spin access. In our case, rectangular 60-90 GHz (E-band) waveguides guarantee low-loss supply of microwaves to the resonators. Three dimensional cavities, as well as coplanar waveguide resonators, enhance MW fields by spatial and spectral confinement with a MW efficiency of 1.36 mT/?W. We utilize single nitrogen vacancy (NV) centers as hosts for optically accessible spins and show that their properties regarding optical spin readout known from smaller fields (<0.65 T) are retained up to fields of 3 T. In addition, we demonstrate coherent control of single nuclear spins under these conditions. Furthermore, our results extend the applicable magnetic field range of a single spin magnetic field sensor. Regarding spin based quantum registers, high fields lead to a purer product basis of electron and nuclear spins, which promises improved spin lifetimes. For example, during continuous single-shot readout, the (14)N nuclear spin shows second-long longitudinal relaxation times. PMID- 26133856 TI - Unidirectional rotating coordinate rotation digital computer algorithm based on rotational phase estimation. AB - The improved coordinate rotation digital computer (CORDIC) algorithm gives high precision and resolution phase rotation, but it has some shortages such as high iterations and big system delay. This paper puts forward unidirectional rotating CORDIC algorithm to solve these problems. First, using under-damping theory, a part of unidirectional phase rotations is carried out. Then, the threshold value of angle is determined based on phase rotation estimation method. Finally, rotation phase estimation completes the rest angle iterations. Furthermore, the paper simulates and implements the numerical control oscillator by Quartus II software and Modelsim software. According to the experimental results, the algorithm reduces iterations and judgment of sign bit, so that it decreases system delay and resource utilization and improves the throughput. We always analyze the error brought by this algorithm. It turned out that the algorithm has a good application prospect in global navigation satellite system and channelized receiver. PMID- 26133857 TI - Real-time implementation of frequency-modulated continuous-wave synthetic aperture radar imaging using field programmable gate array. AB - A new miniature linear frequency-modulated continuous-wave radar which mounted on an unmanned aerial vehicle is presented. It allows the accomplishment of high resolution synthetic aperture radar imaging in real-time. Only a Kintex-7 field programmable gate array from Xilinx is utilized for whole signal processing of sophisticated radar imaging algorithms. The proposed hardware architecture achieves remarkable improvement in integration, power consumption, volume, and computing performance over its predecessor designs. The realized design is verified by flight campaigns. PMID- 26133858 TI - Development of 600 kV triple resonance pulse transformer. AB - In this paper, a triple-resonance pulse transformer based on an air-core transformer is introduced. The voltage across the high-voltage winding of the air core transformer is significantly less than the output voltage; instead, the full output voltage appears across the tuning inductor. The maximum ratio of peak load voltage to peak transformer voltage is 2.77 in theory. By analyzing pulse transformer's lossless circuit, the analytical expression for the output voltage and the characteristic equation of the triple-resonance circuit are presented. Design method for the triple-resonance pulse transformer (iterated simulation method) is presented, and a triple-resonance pulse transformer is developed based on the existing air-core transformer. The experimental results indicate that the maximum ratio of peak voltage across the load to peak voltage across the high voltage winding of the air-core transformer is approximately 2.0 and the peak output voltage of the triple-resonance pulse transformer is approximately 600 kV. PMID- 26133860 TI - Electropyroelectric technique: A methodology free of fitting procedures for thermal effusivity determination in liquids. AB - This paper describes an alternative methodology to determine the thermal effusivity of a liquid sample using the recently proposed electropyroelectric technique, without fitting the experimental data with a theoretical model and without having to know the pyroelectric sensor related parameters, as in most previous reported approaches. The method is not absolute, because a reference liquid with known thermal properties is needed. Experiments have been performed that demonstrate the high reliability and accuracy of the method with measurement uncertainties smaller than 3%. PMID- 26133859 TI - Modelling, verification, and calibration of a photoacoustics based continuous non invasive blood glucose monitoring system. AB - This paper examines the use of photoacoustic spectroscopy (PAS) at an excitation wavelength of 905 nm for making continuous non-invasive blood glucose measurements. The theoretical background of the measurement technique is verified through simulation. An apparatus is fabricated for performing photoacoustic measurements in vitro on glucose solutions and in vivo on human subjects. The amplitude of the photoacoustic signals measured from glucose solutions is observed to increase with the solution concentration, while photoacoustic amplitude obtained from in vivo measurements follows the blood glucose concentration of the subjects, indicating a direct proportionality between the two quantities. A linear calibration method is applied separately on measurements obtained from each individual in order to estimate the blood glucose concentration. The estimated glucose values are compared to reference glucose concentrations measured using a standard glucose meter. A plot of 196 measurement pairs taken over 30 normal subjects on a Clarke error grid gives a point distribution of 82.65% and 17.35% over zones A and B of the grid with a mean absolute relative deviation (MARD) of 11.78% and a mean absolute difference (MAD) of 15.27 mg/dl (0.85 mmol/l). The results obtained are better than or comparable to those obtained using photoacoustic spectroscopy based methods or other non invasive measurement techniques available. The accuracy levels obtained are also comparable to commercially available continuous glucose monitoring systems. PMID- 26133861 TI - Characterization of rectangular vertical cracks using burst vibrothermography. AB - We use burst vibrothermography to characterize, i.e., to determine the dimensions and location of buried vertical cracks of rectangular shape. Surface breaking as well as buried cracks are investigated. We calculate the surface temperature distribution generated by a rectangular vertical crack when excited by an ultrasound burst of constant power. By fitting synthetic data with added white noise, we analyze the effect of the burst duration on the accuracy of the retrieved dimensions and depth of the crack. We take data on samples containing artificial calibrated vertical cracks. The results of the fittings performed on these experimental data show that it is possible to characterize rectangular vertical cracks from burst vibrothermography experiments. PMID- 26133862 TI - High resolution quartz flexure accelerometer based on laser self-mixing interferometry. AB - As common high-precision inertial sensors, quartz flexure accelerometers have a wide application prospect in low-cost inertial navigation systems. To ameliorate their resolution performance restricted by differential capacitance detection, we proposed a modified type of quartz flexure accelerometer based on an emerging optical technique named laser self-mixing interferometry, which is utilized to sense the displacement of a quartz pendulous reed, and then an equal and opposite force is accordingly produced to maintain the reed motionless relative to the inertial frame. The configuration and working principle of the improved accelerometer have been introduced and analyzed. The preliminary experiments indicate that its bias stability reaches 0.75-0.85 MUg, which shows some progress when compared to the traditional type. Further improvements are mainly limited by the characteristics of the laser diode and the multiple reflections from the pendulous reed. PMID- 26133863 TI - Novel method for estimating the dynamic characteristics of pressure sensor in shock tube calibration test. AB - A shock tube is usually used to excite the dynamic characteristics of the pressure sensor used in an aircraft. This paper proposes a novel estimation method for determining the dynamic characteristic parameters of the pressure sensor. A preprocessing operation based on Grey Model [GM(1,1)] and bootstrap method (BM) is employed to analyze the output of a calibrated pressure sensor under step excitation. Three sequences, which include the estimated value sequence, upper boundary, and lower boundary, are obtained. The processing methods on filtering and modeling are used to explore the three sequences independently. The optimal estimated, upper boundary, and lower boundary models are then established. The three models are solved, and a group of dynamic characteristic parameters corresponding to the estimated intervals are obtained. A shock tube calibration test consisting of two experiments is performed to validate the performance of the proposed method. The results show that the relative errors of the dynamic characteristic parameters of time and frequency domains do not exceed 9% and 10%, respectively. Moreover, the nominal and estimated values of the parameters fall into the estimated intervals limited by the upper and lower values. PMID- 26133864 TI - Design of a MEMS piezoresistive differential pressure sensor with small thermal hysteresis for air data modules. AB - The design, fabrication, and evaluation results of a MEMS piezoresistive differential pressure sensor fabricated by the dry etching process are described in this paper. The proposed sensor is designed to have optimal performances in mid-pressure range from 0 psi to 20 psi suitable for a precision air data module. The piezoresistors with a Wheatstone bridge structure are implanted where the thermal effects are minimized subject to sustainment of the sensitivity. The rectangular-shaped silicon diaphragm is adopted and its dimension is analyzed for improving pressure sensitivity and linearity. The bridge resistors are driven by constant current to compensate temperature effects on sensitivity. The designed differential pressure sensor is fabricated by using MEMS dry etching techniques, and the fabricated sensing element is attached and packaged in a Kovar package in consideration of leakage and temperature hysteresis. The implemented sensors are tested and evaluated as well. The evaluation results show the static RSS (root sum square) accuracy including nonlinearity, non-repeatability, and pressure hysteresis before temperature compensation is about 0.09%, and the total error band which includes the RSS accuracy, the thermal hysteresis, and other thermal effects is about 0.11%, which confirm the validity of the proposed design process. PMID- 26133865 TI - Multiplexed displacement fiber sensor using thin core fiber exciter. AB - This letter reports a multiplexed optical displacement sensor using a thin core fiber (TCF) exciter. The TCF exciter is followed by a stripped single mode optical fiber. A small section of buffer is used as the movable component along the single mode fiber. Ultra-weak cladding mode reflection (< - 75 dB) was employed to probe the refractive index discontinuity between the air and buffer coating boundary. The position change of the movable buffer segment results in a delay change of the cladding mode reflection. Thus, it is a measure of the displacement of the buffer segment with respect to the glass fiber. The insertion loss of one sensor was measured to be less than 3 dB. A linear relationship was evaluated between the measurement position and absolute position of the moving actuator. Multiplexed capability was demonstrated and no cross talk was found between the sensors. PMID- 26133866 TI - Fuzzy multi-objective optimization for movement performance of deep-notch elliptical flexure hinges. AB - Compared with commonly used flexure hinges, deep-notch elliptical flexure hinges are more suitable for flexible mechanisms with high precise transmission requirements. The rotation stiffness model of deep-notch elliptical flexure hinges was built first, and the compliance matrix was analyzed and solved by using Newton-Cotes quadrature formula to simplify the calculation of compliance coefficients; on the other hand, the fuzzy multi-objective optimization model with distribution was constructed, and a detailed example was given out to validate the effectiveness of the fuzzy optimization. The experiment results show that the desired angular displacement alpha(z) around the z axis is increased by 30.13%; while the undesired alpha(y) that around the y axis is decreased by 15.74% in experiment. The line displacements of Delta(y) and Delta(z) along the Y and Z axes are decreased by 18.15% and 47.69%, respectively. All the optimization data show that after the fuzzy optimization, the rotation capacity of z axis has been raised, and the motion capacity of the undesired directions has been restrained, so that the movement precision and the performance of the deep-notch elliptical flexure hinge can be improved, which is more suitable for the optical waveguide packaging positioning platform with high precision transmission. PMID- 26133867 TI - Lithographically fabricated silicon microreactor for in situ characterization of heterogeneous catalysts-Enabling correlative characterization techniques. AB - We report on a new modular setup on a silicon-based microreactor designed for correlative spectroscopic, scattering, and analytic on-line gas investigations for in situ studies of heterogeneous catalysts. The silicon microreactor allows a combination of synchrotron radiation based techniques (e.g., X-ray diffraction and X-ray absorption spectroscopy) as well as infrared thermography and Raman spectroscopy. Catalytic performance can be determined simultaneously by on-line product analysis using mass spectrometry. We present the design of the reactor, the experimental setup, and as a first example for an in situ study, the catalytic partial oxidation of methane showing the applicability of this reactor for in situ studies. PMID- 26133868 TI - Fast pulsed operation of a small non-radioactive electron source with continuous emission current control. AB - Non-radioactive electron sources are of great interest in any application requiring the emission of electrons at atmospheric pressure, as they offer better control over emission parameters than radioactive electron sources and are not subject to legal restrictions. Recently, we published a simple electron source consisting only of a vacuum housing, a filament, and a single control grid. In this paper, we present improved control electronics that utilize this control grid in order to focus and defocus the electron beam, thus pulsing the electron emission at atmospheric pressure. This allows short emission pulses and excellent stability of the emitted electron current due to continuous control, both during pulsed and continuous operations. As an application example, this electron source is coupled to an ion mobility spectrometer. Here, the pulsed electron source allows experiments on gas phase ion chemistry (e.g., ion generation and recombination kinetics) and can even remove the need for a traditional ion shutter. PMID- 26133869 TI - Efficient scalable solid-state neutron detector. AB - We report on scalable solid-state neutron detector system that is specifically designed to yield high thermal neutron detection sensitivity. The basic detector unit in this system is made of a (6)Li foil coupled to two crystalline silicon diodes. The theoretical intrinsic efficiency of a detector-unit is 23.8% and that of detector element comprising a stack of five detector-units is 60%. Based on the measured performance of this detector-unit, the performance of a detector system comprising a planar array of detector elements, scaled to encompass effective area of 0.43 m(2), is estimated to yield the minimum absolute efficiency required of radiological portal monitors used in homeland security. PMID- 26133870 TI - Versatile atomic force microscopy setup combined with micro-focused X-ray beam. AB - Micro-focused X-ray beams produced by third generation synchrotron sources offer new perspective of studying strains and processes at nanoscale. Atomic force microscope setup combined with a micro-focused synchrotron beam allows precise positioning and nanomanipulation of nanostructures under illumination. In this paper, we report on integration of a portable commercial atomic force microscope setup into a hard X-ray synchrotron beamline. Details of design, sample alignment procedure, and performance of the setup are presented. PMID- 26133871 TI - Development and application of an apparatus for high-temperature measurement of magnetic susceptibility. AB - An apparatus for high-temperature measurement of magnetic susceptibility using the modified Gouy method was developed. It can be used at temperatures of up to 1200 degrees C. The apparatus consists of the heating system, weighing system, and temperature-programming controller. The sample should be placed at a position of relatively constant B(dB/dz) in a gradient magnetic field. Each crucible is used only once for a single measurement to reduce the error. The reliable accuracy and good repeatability of the apparatus are demonstrated by measuring the magnetic susceptibilities of a DD483 superalloy, Ni-based solid solution alloy, and Ni3Al-based solid solution alloy at various temperatures. The results also successfully explain the change in the gamma' precipitation in DD483 superalloys. Therefore, the apparatus provides a convenient and powerful tool for investigating high-temperature phase transitions in the presence of a magnetic field. PMID- 26133873 TI - 3D-printed slit nozzles for Fourier transform microwave spectroscopy. AB - 3D printing is a new technology whose applications are only beginning to be explored. In this report, we describe the application of 3D printing to the design and construction of supersonic nozzles. Nozzles can be created for $0.50 or less, and the ease and low cost can facilitate the optimization of nozzle performance for the needs of any particular experiment. The efficacy of a variety of designs is assessed by examining rotational spectra of OCS (carbonyl sulfide) and Ar-OCS using a Fourier transform microwave spectrometer with tandem cavity and chirped-pulse capabilities. A slit geometry which, to the best of our knowledge has not been used in conjunction with Fourier transform microwave spectrometers, was found to increase the signal-to-noise ratio for the J = 1<-0 transition of OCS, by a factor of three to four compared with that obtained using our standard circular nozzle. Corresponding gains for the Ar-OCS complex were marginal, at best, but further optimization of nozzle geometry should be possible. The spectrometer itself is designed to allow rapid switching between cavity and chirped-pulse modes of operation without the need to break vacuum. This feature, as well as the newly incorporated chirped-pulse capability, is described in detail. PMID- 26133872 TI - ChiMS: Open-source instrument control software platform on LabVIEW for imaging/depth profiling mass spectrometers. AB - ChiMS is an open-source data acquisition and control software program written within LabVIEW for high speed imaging and depth profiling mass spectrometers. ChiMS can also transfer large datasets from a digitizer to computer memory at high repetition rate, save data to hard disk at high throughput, and perform high speed data processing. The data acquisition mode generally simulates a digital oscilloscope, but with peripheral devices integrated for control as well as advanced data sorting and processing capabilities. Customized user-designed experiments can be easily written based on several included templates. ChiMS is additionally well suited to non-laser based mass spectrometers imaging and various other experiments in laser physics, physical chemistry, and surface science. PMID- 26133874 TI - The boiling Twente Taylor-Couette (BTTC) facility: Temperature controlled turbulent flow between independently rotating, coaxial cylinders. AB - A new Taylor-Couette system has been designed and constructed with precise temperature control. Two concentric independently rotating cylinders are able to rotate at maximum rates of f(i) = +/- 20 Hz for the inner cylinder and f(o) = +/- 10 Hz for the outer cylinder. The inner cylinder has an outside radius of r(i) = 75 mm, and the outer cylinder has an inside radius of r(o) = 105 mm, resulting in a gap of d = 30 mm. The height of the gap is L = 549 mm, giving a volume of V = 9.3 L. The geometric parameters are eta = r(i)/r(o) = 0.714 and Gamma = L/d = 18.3. With water as working fluid at room temperature, the Reynolds numbers that can be achieved are Re(i) = omega(i)r(i)(r(o) - r(i))/nu = 2.8 * 10(5) and Re(o) = omega(o)r(o)(r(o) - r(i))/nu = 2 * 10(5) or a combined Reynolds number of up to Re = (omega(i)r(i) - omega(o)r(o))(r(o) - r(i))/nu = 4.8 * 10(5). If the working fluid is changed to the fluorinated liquid FC-3284 with kinematic viscosity 0.42 cSt, the combined Reynolds number can reach Re = 1.1 * 10(6). The apparatus features precise temperature control of the outer and inner cylinders separately and is fully optically accessible from the side and top. The new facility offers the possibility to accurately study the process of boiling inside a turbulent flow and its effect on the flow. PMID- 26133875 TI - A cable-driven wrist robotic rehabilitator using a novel torque-field controller for human motion training. AB - Rehabilitation technologies have great potentials in assisted motion training for stroke patients. Considering that wrist motion plays an important role in arm dexterous manipulation of activities of daily living, this paper focuses on developing a cable-driven wrist robotic rehabilitator (CDWRR) for motion training or assistance to subjects with motor disabilities. The CDWRR utilizes the wrist skeletal joints and arm segments as the supporting structure and takes advantage of cable-driven parallel design to build the system, which brings the properties of flexibility, low-cost, and low-weight. The controller of the CDWRR is designed typically based on a virtual torque-field, which is to plan "assist-as-needed" torques for the spherical motion of wrist responding to the orientation deviation in wrist motion training. The torque-field controller can be customized to different levels of rehabilitation training requirements by tuning the field parameters. Additionally, a rapidly convergent parameter self-identification algorithm is developed to obtain the uncertain parameters automatically for the floating wearable structure of the CDWRR. Finally, experiments on a healthy subject are carried out to demonstrate the performance of the controller and the feasibility of the CDWRR on wrist motion training or assistance. PMID- 26133876 TI - Note: Real time optical sensing of alpha-radiation emitting radioactive aerosols based on solid state nuclear track detector. AB - A sensitive radioactive aerosols sensor has been designed and developed. Its design guidance is based on the need for a low operational cost and reliable measurements to provide daily aerosol monitoring. The exposure of diethylene glycol bis (allylcarbonate) to radiation causes modification of its physico chemical properties like surface roughness and reflectance. In the present study, optical sensor based on the reflectance measurement has been developed with an aim to monitor real time presence of alpha radioactive aerosols emitted from thorium nitrate hydrate. The results shows that the fabricated sensor can detect 0.0157 kBq to 0.1572 kBq of radio activity by radioactive aerosols generated from (Th(NO3)4 ? 5H2O) at 0.1 ml/min flow rate. The proposed instrument will be helpful to monitor radioactive aerosols in/around a nuclear facility, building construction sites, mines, and granite polishing factories. PMID- 26133877 TI - Note: Enhanced energy harvesting from low-frequency magnetic fields utilizing magneto-mechano-electric composite tuning-fork. AB - A magnetic-field energy harvester using a low-frequency magneto-mechano-electric (MME) composite tuning-fork is proposed. This MME composite tuning-fork consists of a copper tuning fork with piezoelectric Pb(Zr(1-x)Ti(x))O3 (PZT) plates bonded near its fixed end and with NdFeB magnets attached at its free ends. Due to the resonance coupling between fork prongs, the MME composite tuning-fork owns strong vibration and high Q value. Experimental results show that the proposed magnetic field energy harvester using the MME composite tuning-fork exhibits approximately 4 times larger maximum output voltage and 7.2 times higher maximum power than the conventional magnetic-field energy harvester using the MME composite cantilever. PMID- 26133878 TI - Note: Device for underwater laboratory simulation of unconfined blast waves. AB - Shock tubes simulate blast waves to study their effects in air under laboratory conditions; however, few experimental models exist for simulating underwater blast waves that are needed for facilitating experiments in underwater blast transmission, determining injury thresholds in marine animals, validating numerical models, and exploring mitigation strategies for explosive well removals. This method incorporates an oxy-acetylene driven underwater blast simulator which creates peak blast pressures of about 1860 kPa. Shot-to-shot consistency was fair, with an average standard deviation near 150 kPa. Results suggest that peak blast pressures from 460 kPa to 1860 kPa are available by adjusting the distance from the source. PMID- 26133879 TI - Note: Improving low-light-level image detection sensitivity with higher speed using auxiliary sinusoidal light signal. AB - An improved active imaging method, which upgraded the detection sensitivity by applying an auxiliary sawtooth wave light signal, was reported. Nevertheless, such method sacrificed the imaging speed. To speed up imaging, a sinusoidal light signal is used instead and superposed with the undetectable low-light-level signal on the image sensor. After acquiring a superimposed image set in one sine wave cycle, an unbiased low-light-level image estimation is obtained by using least-square optimization. Through probabilistic analysis and experimental study, we demonstrate that the sinusoidal signal could improve the detection sensitivity 1/3 faster than the sawtooth wave signal. PMID- 26133880 TI - Note: On the wavelength dependence of the intensity calibration factor of extreme ultraviolet spectrometer determined with profile measurement of bremsstrahlung continuum. AB - The absolute calibration factor of extreme ultraviolet spectroscopic instrument which has recently been determined from absolute radiation profile measurement of bremsstrahlung continuum has been investigated by comparing the calculated diffraction efficiency of grating. An overall tendency of the wavelength dependence of the calibration factor from 40 A to 500 A can be reproduced by that of the grating efficiency, especially the agreement between the measured calibration factor and the calculated grating efficiency has been found to be fairly good for the wavelength range 200 A-500 A. PMID- 26133881 TI - Note: A single-chamber tool for plasma activation and surface functionalization in microfabrication. AB - We present a simple apparatus for improved surface modification of polydimethylsiloxane (PDMS) microfluidic devices. A single treatment chamber for plasma activation and chemical/physical vapor deposition steps minimizes the time dependent degradation of surface activation that is inherent in multi-chamber techniques. Contamination and deposition irregularities are also minimized by conducting plasma activation and treatment phases in the same vacuum environment. An inductively coupled plasma driver allows for interchangeable treatment chambers. Atomic force microscopy confirms that silane deposition on PDMS gives much better surface quality than standard deposition methods, which yield a higher local roughness and pronounced irregularities in the surface. PMID- 26133882 TI - Note: Using fast digitizer acquisition and flexible resolution to enhance noise cancellation for high performance nanosecond transient absorbance spectroscopy. AB - We demonstrate a nanosecond transient absorbance spectrometer that utilizes flexible resolution and rapid data acquisition triggering modes. The instrument features signal-to-noise (S/N) levels enhanced by an order of magnitude especially within the first 100 ns. The primary gain in S/N comes from our sequential subtraction method, which requires a fast digitizer trigger rearm time to detect every laser trigger event. PMID- 26133883 TI - Note: A high-efficiency multi-coincidence method designed for molecular fragmentation studies. AB - A high-efficiency multi-coincidence method is developed based on the hardware electronic multiple coincidence units. The multi-hit signals originating from one single detector can be selected and measured in coincidence. The performance of the method is tested by the electron impact three-body fragmentation of CO2(3+). Compared to the conventional method, the relative and absolute coincidence efficiencies of the triple-coincidence measurement are improved by about 200 and 3 times, respectively. PMID- 26133884 TI - Note: A non-invasive electronic measurement technique to measure the embedded four resistive elements in a Wheatstone bridge sensor. AB - The work shows a measurement technique to obtain the correct value of the four elements in a resistive Wheatstone bridge without the need to separate the physical connections existing between them. Two electronic solutions are presented, based on a source-and-measure unit and using discrete electronic components. The proposed technique brings the possibility to know the mismatching or the tolerance between the bridge resistive elements and then to pass or reject it in terms of its related common-mode rejection. Experimental results were taken in various Wheatstone resistive bridges (discrete and magnetoresistive integrated bridges) validating the proposed measurement technique specially when the bridge is micro-fabricated and there is no physical way to separate one resistive element from the others. PMID- 26133886 TI - Erratum: "Momentum resolution in inverse photoemission" [Rev. Sci. Instrum. 86, 013908 (2015)]. PMID- 26133887 TI - Corrigendum: Increased CRF signalling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal. PMID- 26133888 TI - Erratum to: Ethical Considerations of Physician Career Involvement in Global Health Work: A Framework. PMID- 26133889 TI - Reproductive Ethics in Commercial Surrogacy: Decision-Making in IVF Clinics in New Delhi, India. AB - As a neo-liberal economy, India has become one of the new health tourism destinations, with commercial gestational surrogacy as an expanding market. Yet the Indian Assisted Reproductive Technology (ART) Bill has been pending for five years, and the guidelines issued by the Indian Council of Medical Research are somewhat vague and contradictory, resulting in self-regulated practices of fertility clinics. This paper broadly looks at clinical ethics in reproduction in the practice of surrogacy and decision-making in various procedures. Through empirical research in New Delhi, the capital of India, from December 2011 to November 2012, issues of decision-making on embryo transfer, fetal reduction, and mode of delivery were identified. Interviews were carried out with doctors in eighteen ART clinics, agents from four agencies, and fourteen surrogates. In aiming to fulfil the commissioning parents' demands, doctors were willing to go to the greatest extent possible in their medical practice. Autonomy and decision making regarding choice of the number of embryos to transfer and the mode of delivery lay neither with commissioning parents nor surrogate mothers but mostly with doctors. In order to ensure higher success rates, surrogates faced the risk of multiple pregnancy and fetal reduction with little information regarding the risks involved. In the globalized market of commercial surrogacy in India, and with clinics compromising on ethics, there is an urgent need for formulation of regulative law for the clinical practice and maintenance of principles of reproductive ethics in order to ensure that the interests of surrogate mothers are safeguarded. PMID- 26133890 TI - Conflicts Between Parents and Health Professionals About a Child's Medical Treatment: Using Clinical Ethics Records to Find Gaps in the Bioethics Literature. AB - Clinical ethics records offer bioethics researchers a rich source of cases that clinicians have identified as ethically complex. In this paper, we suggest that clinical ethics records can be used to point to types of cases that lack attention in the current bioethics literature, identifying new areas in need of more detailed bioethical work. We conducted an analysis of the clinical ethics records of one paediatric hospital in Australia, focusing specifically on conflicts between parents and health professionals about a child's medical treatment. We identified, analysed, and compared cases of this type from the clinical ethics records with cases of this type discussed in bioethics journals. While the cases from journals tended to describe situations involving imminent risk to the child's life, a significant proportion of the clinical ethics records cases involved different stakes for the child involved. These included distress, poorer functional outcome, poorer psychosocial outcome, or increased risk of surgical complications. Our analysis suggests that one type of case that warrants more detailed ethics research is parental refusal of recommended treatment, where the refusal does not endanger the child's life but rather some other aspect of the child's well-being. PMID- 26133891 TI - The Tortoise Transformation as a Prospect for Life Extension. AB - The value of extending the human lifespan remains a key philosophical debate in bioethics. In building a case against the extension of the species-typical human life, Nicolas Agar considers the prospect of transforming human beings near the end of their lives into Galapagos tortoises, which would then live on decades longer. A central question at stake in this transformation is the persistence of human consciousness as a condition of the value of the transformation. Agar entertains the idea that consciousness could persist in some measure, but he thinks little is to be gained from the transformation because the experiences available to tortoises pale in comparison to those available to human beings. Moreover, he thinks persisting human consciousness and values would degrade over time, being remade by tortoise needs and environment. The value available in the transformation would not, then, make the additional years of life desirable. Agar's account does not, however, dispose of the tortoise transformation as a defensible preference. Some people might still want this kind of transformation for symbolic reasons, but it would probably be better that no human consciousness persist, since that consciousness would be inexpressible as such. Even so, it is not irrational to prefer various kinds of lifespan extension even if they involve significant modifications to human consciousness and values. PMID- 26133892 TI - Surrogacy, Compensation, and Legal Parentage: Against the Adoption Model. AB - Surrogate motherhood is treated as a form of adoption in many countries: the birth mother and her partner are presumed to be the parents of the child, while the intended parents have to adopt the baby once it is born. Other than compensation for expenses related to the pregnancy, payment to surrogates is not permitted. We believe that the failure to compensate surrogate mothers for their labour as well as the significant risks they undertake is both unfair and exploitative. We accept that introducing payment for surrogates would create a significant tension in the adoption model. However, we recommend rejecting the adoption model altogether rather than continuing to prohibit compensation to surrogates. PMID- 26133893 TI - Teaching Conflict: Professionalism and Medical Education. AB - Resistance by physicians, medical researchers, medical educators, and medical students to pharmaceutical industry influence in medicine is often based on the notion that physicians (guided by the ethics of their profession) and the industry (guided by profit) are in conflict. This criticism has taken the form of a professional movement opposing conflict of interest (COI) in medicine and medical education and has resulted in policies and guidelines that frame COI as the problem and outline measures to address this problem. In this paper, I offer a critique of this focus on COI that is grounded in a broader critique of neo liberalism, arguing it individualizes the relationship between physicians and industry, too neatly delineates between the two entities, and reduces the network of social, economic, and political relations to this one dilemma. PMID- 26133894 TI - Preparing a collection of radiology examinations for distribution and retrieval. AB - OBJECTIVE: Clinical documents made available for secondary use play an increasingly important role in discovery of clinical knowledge, development of research methods, and education. An important step in facilitating secondary use of clinical document collections is easy access to descriptions and samples that represent the content of the collections. This paper presents an approach to developing a collection of radiology examinations, including both the images and radiologist narrative reports, and making them publicly available in a searchable database. MATERIALS AND METHODS: The authors collected 3996 radiology reports from the Indiana Network for Patient Care and 8121 associated images from the hospitals' picture archiving systems. The images and reports were de-identified automatically and then the automatic de-identification was manually verified. The authors coded the key findings of the reports and empirically assessed the benefits of manual coding on retrieval. RESULTS: The automatic de-identification of the narrative was aggressive and achieved 100% precision at the cost of rendering a few findings uninterpretable. Automatic de-identification of images was not quite as perfect. Images for two of 3996 patients (0.05%) showed protected health information. Manual encoding of findings improved retrieval precision. CONCLUSION: Stringent de-identification methods can remove all identifiers from text radiology reports. DICOM de-identification of images does not remove all identifying information and needs special attention to images scanned from film. Adding manual coding to the radiologist narrative reports significantly improved relevancy of the retrieved clinical documents. The de identified Indiana chest X-ray collection is available for searching and downloading from the National Library of Medicine (http://openi.nlm.nih.gov/). PMID- 26133895 TI - Impact of electronic diabetes registry 'Meaningful Use' on quality of care and hospital utilization. AB - OBJECTIVE: To investigate whether the use of diabetes registries meeting Meaningful Use core objectives in primary care practices is associated with differences in quality of care and hospital utilization rates. MATERIALS AND METHODS: A practice assessment survey was conducted to identify whether and how practices were using diabetes registries. Insurance claims data from 2010 were used to compare the health outcomes of patients from practices that used diabetes registries meeting Meaningful Use-related objectives to the outcomes of patients from other practices. Logistic hierarchical linear modeling was used to analyze the data. RESULTS: Records from 12,514 diabetic patients (including 10,809 with type 2 diabetes) from 50 urban practices were included in the analysis. The results suggest that patients with type 2 diabetes who were treated in practices using registries for patient reminders were more likely to have completed the recommended laboratory testing (odds ratio [OR] 1.26, p < 0.01) and dilated retinal examinations (OR 1.14, p < 0.01). Patients in practices using registries for quality improvement were less likely to have 'avoidable hospitalization' (OR 0.83, p < 0.01) and emergency room visits (OR 0.76, p < 0.01). The use of a diabetes registry did not have a significant impact on the quality of care or hospital utilization for patients with type 1 diabetes. CONCLUSION: Use of diabetes registries meeting Meaningful Use core objectives is associated with higher completion or recommended lab tests and a lower hospital utilization rate for patients with type 2 diabetes. PMID- 26133896 TI - Association between left ventricular global longitudinal strain, health-related quality of life and functional capacity in chronic kidney disease patients with preserved ejection fraction. AB - AIM: Patients with chronic kidney disease (CKD) have a significant burden of dyspnoea and fatigue in spite having normal left ventricular (LV) ejection fraction (EF). Global longitudinal strain (GLS) can detect subtle changes in LV function. This study aimed to evaluate the relationship between LV function, functional capacity and quality of life (QOL) in CKD patients with preserved EF. METHODS: A cross-sectional study of patients with stage 3/4 CKD (n = 108). Clinical characteristics, biochemical data, functional capacity (6-min walk test (6MWT), timed up and go (TUG) test) and QOL (short form-12 (SF-12v2TM) ) were measured. Echocardiogram was used to assess GLS, EF and diastolic function (E/A, e' and E/e'). RESULTS: The mean age was 58.1 +/- 9.9 years, 55.6% were men, estimated glomerular filtration rate was 44.8 +/- 10.6 mL/min/1.73 m(2), GLS was 18.5 +/- 3.6% and 19.4% had impaired GLS (>-16%). Patients with impaired GLS had a significantly shorter 6MWT and slower TUG test compared with patients with preserved GLS. Bivariate analysis showed GLS and E/e' correlated with distance walked in 6MWT (GLS (r = -0.24, P = 0.02); E/e'(r = -0.38, P = 0.002) ). Following adjustment for potential confounders, GLS remained independently associated with 6MWT (model R(2) = 0.37, P < 0.001). Mean physical component summary scores (PCS) and mental component summary scores (MCS) were 43.0 +/- 10.2 and 50.9 +/- 9.5. There was no cardiac parameter that was independently associated with PCS. However women, lower systolic blood pressure and GLS was associated with lower MCS (model R(2) = 0.30, P < 0.001). CONCLUSION: GLS was associated with measures of functional capacity and QOL in CKD patients with preserved EF. PMID- 26133897 TI - The Hairless Stem Phenotype of Cotton (Gossypium barbadense) Is Linked to a Copia Like Retrotransposon Insertion in a Homeodomain-Leucine Zipper Gene (HD1). AB - Cotton (Gossypium) stem trichomes are mostly single cells that arise from stem epidermal cells. In this study, a homeodomain-leucine zipper gene (HD1) was found to cosegregate with the dominant trichome locus previously designated as T1 and mapped to chromosome 6. Characterization of HD1 orthologs revealed that the absence of stem trichomes in modern Gossypium barbadense varieties is linked to a large retrotransposon insertion in the ninth exon, 2565 bp downstream from the initial codon in the At subgenome HD1 gene (At-GbHD1). In both the At and Dt subgenomes, reduced transcription of GbHD1 genes is caused by this insertion. The disruption of At-HD1 further affects the expression of downstream GbMYB25 and GbHOX3 genes. Analyses of primitive cultivated accessions identified another retrotransposon insertion event in the sixth exon of At-GbHD1 that might predate the previously identified retrotransposon in modern varieties. Although both retrotransposon insertions results in similar phenotypic changes, the timing of these two retrotransposon insertion events fits well with our current understanding of the history of cotton speciation and dispersal. Taken together, the results of genetics mapping, gene expression and association analyses suggest that GbHD1 is an important component that controls stem trichome development and is a promising candidate gene for the T1 locus. The interspecific phenotypic difference in stem trichome traits also may be attributable to HD1 inactivation associated with retrotransposon insertion. PMID- 26133898 TI - Alternative intubation techniques vs Macintosh laryngoscopy in patients with cervical spine immobilization: systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Immobilization of the cervical spine worsens tracheal intubation conditions. Various intubation devices have been tested in this setting. Their relative usefulness remains unclear. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library for randomized controlled trials comparing any intubation device with the Macintosh laryngoscope in human subjects with cervical spine immobilization. The primary outcome was the risk of tracheal intubation failure at the first attempt. Secondary outcomes were quality of glottis visualization, time until successful intubation, and risk of oropharyngeal complications. RESULTS: Twenty-four trials (1866 patients) met inclusion criteria. With alternative intubation devices, the risk of intubation failure was lower compared with Macintosh laryngoscopy [risk ratio (RR) 0.53; 95% confidence interval (CI) 0.35-0.80]. Meta-analyses could be performed for five intubation devices (Airtraq, Airwayscope, C-Mac, Glidescope, and McGrath). The Airtraq was associated with a statistically significant reduction of the risk of intubation failure at the first attempt (RR 0.14; 95% CI 0.06-0.33), a higher rate of Cormack-Lehane grade 1 (RR 2.98; 95% CI 1.94-4.56), a reduction of time until successful intubation (weighted mean difference -10.1 s; 95% CI -3.2 to -17.0), and a reduction of oropharyngeal complications (RR 0.24; 95% CI 0.06-0.93). Other devices were associated with improved glottis visualization but no statistically significant differences in intubation failure or time to intubation compared with conventional laryngoscopy. CONCLUSIONS: In situations where the spine is immobilized, the Airtraq device reduces the risk of intubation failure. There is a lack of evidence for the usefulness of other intubation devices. PMID- 26133899 TI - Detection of UV-induced cyclobutane pyrimidine dimers by near-infrared spectroscopy and aquaphotomics. AB - Ultraviolet (UV) radiation causes cellular DNA damage, among which cyclobutane pyrimidine dimers (CPDs) are responsible for a variety of genetic mutations. Although several approaches have been developed for detection of CPDs, conventional methods require time-consuming steps. Aquaphotomics, a new approach based on near-infrared spectroscopy (NIRS) and multivariate analysis that determines interactions between water and other components of the solution, has become an effective method for qualitative and quantitative parameters measurement in the solutions. NIR spectral patterns of UVC-irradiated and nonirradiated DNA solutions were evaluated using aquaphotomics for detection of UV-induced CPDs. Groups of UV-irradiated and nonirradiated DNA samples were classified (87.5% accuracy) by soft independent modeling of class analogy (SIMCA). A precise regression model calculated from NIR water spectral patterns based on UVC doses (r Val = 0.9457) and the concentration of cis-syn cyclobutane thymine dimers (cis-syn T<>Ts; r Val = 0.9993) was developed using partial least squares regression (PLSR), while taking advantage of water spectral patterns, particularly around 1400-1500 nm. Our results suggested that, in contrast to DNA, the formation of cis-syn T<>Ts increased the strongly hydrogen bonded water. Additionally, NIRS could qualitatively and quantitatively detect cis-syn T<>Ts in isolated DNA aqueous solutions upon UVC exposure. PMID- 26133900 TI - Islands within islands: two montane palaeo-endemic birds impacted by recent anthropogenic fragmentation. AB - Anthropogenic habitat fragmentation of species that live in naturally patchy metapopulations such as mountaintops or sky islands experiences two levels of patchiness. Effects of such multilevel patchiness on species have rarely been examined. Metapopulation theory suggests that patchy habitats could have varied impacts on persistence, dependent on differential migration. It is not known whether montane endemic species, evolutionarily adapted to natural patchiness, are able to disperse between anthropogenic fragments at similar spatial scales as natural patches. We investigated historic and contemporary gene flow between natural and anthropogenic patches across the distribution range of a Western Ghats sky-island-endemic bird species complex. Data from 14 microsatellites for 218 individuals detected major genetic structuring by deep valleys, including one hitherto undescribed barrier. As expected, we found strong effects of historic genetic differentiation across natural patches, but not across anthropogenic fragments. Contrastingly, contemporary differentiation (D(PS)) was higher relative to historic differentiation (F(ST)) in anthropogenic fragments, despite the species' ability to historically traverse shallow valleys. Simulations of recent isolation resulted in high D(PS)/F(ST) values, confirming recent isolation in Western Ghats anthropogenic fragments and also suggesting that this ratio can be used to identifying recent fragmentation in the context of historic connectedness. We suggest that in this landscape, in addition to natural patchiness affecting population connectivity, anthropogenic fragmentation additionally impacts connectivity, making anthropogenic fragments akin to islands within natural islands of montane habitat, a pattern that may be recovered in other sky-island systems. PMID- 26133901 TI - Far from Membranes, BEACH Domains Regulate Stress-Related mRNAs. PMID- 26133902 TI - Efficacy of a Chinese Herbal Medicine in Providing Adequate Relief of Constipation-predominant Irritable Bowel Syndrome: A Randomized Controlled Trial. AB - BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is the most common chronic functional bowel disorder, with few treatment options. IBS affects 10%-20% of the population; as many as 58% of patients have constipation-predominant IBS (IBS-C). We evaluated efficacy and safety of a standardized, specifically formulated Chinese herbal medicine (CHM) preparation in treatment of patients with IBS-C. METHODS: We performed a double-blind trial of 125 patients with IBS-C (according to Rome III criteria), who were recruited from 13 medical centers or clinics in Australia from July 2009 through February 2012. Patients were randomly assigned to groups given a standardized extract of 7 selected CHM ingredients (n = 61) or placebo (controls, n = 64) for 8 weeks (5 capsules, twice daily). Subjects were then followed for 16 weeks. Chemical definition, standardization, and stability testing of the formulation were completed. Subjects completed a self administered, validated binary questionnaire of global symptom improvement at weeks 2, 4, 8, and 16 (primary outcome). Secondary outcomes included results from the self-administered IBS Symptom Severity Scale and the Bristol Stool Form Scale (BSFS), which were completed at weeks 4, 8, and 16. RESULTS: There was statistically and clinically significant (per protocol analyses) improvement among subjects who received CHM (n = 50) vs controls (n = 58) for 8 weeks. A greater proportion of subjects receiving CHM reported adequate relief (P = .010). Compared with controls, the CHM group had improved bowel habits vs controls at week 8, including lower IBS Symptom Severity Scale scores (P < .001), reduced straining during defecation (P = .002), and a significant decrease in hard lumpy stools (P = .031). The CHM group also had increased stool consistency, which was based on the Bristol Stool Form Scale (week 8, P < .001). There was no statistically significant difference between groups in abdominal pain at week 8 (P = .692). The CHM was well-tolerated. CONCLUSIONS: In a prospective, controlled study, CHM reduced symptoms of IBS-C, increased bowel satisfaction and stool consistency, and reduced straining and hard lumpy stools, compared with placebo. Clinical trial registration no: ACTRN12609000558224. PMID- 26133903 TI - Estimation of Glomerular Filtration Rate in Patients With Cirrhosis by Using New and Conventional Filtration Markers and Dimethylarginines. AB - BACKGROUND & AIMS: Equations used to estimate glomerular filtration rate (GFR) are not accurate in patients with cirrhosis. We aimed to develop a new equation to estimate the GFR in subjects with cirrhosis and compare its performance with chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C and creatinine-cystatin C equations, which were derived in populations without cirrhosis. METHODS: From 2010 through 2014, we measured GFR in 103 subjects with cirrhosis based on non-radiolabeled iothalamate plasma clearance. We measured blood levels of creatinine, cystatin C, beta-trace protein, beta2-microglobulin, L-arginine, and symmetric and asymmetric dimethylarginines simultaneously with GFR. Multivariate linear regression analysis was performed to develop models to estimate GFR. Overall accuracy, defined by the root mean square error (RMSE) of our newly developed model to estimate GFR, was compared with that of the CKD-EPI equations. To obtain an unbiased estimate of our new equation to estimate GFR, we used a leave-one-out cross-validation strategy. RESULTS: After we considered all the candidate variables and blood markers of GFR, the most accurate equation we identified to estimate GFR included serum levels of creatinine and cystatin C, as well as patients' age, sex, and race. Overall, the accuracy of this equation (RMSE = 22.92) was superior to that of the CKD-EPI cystatin C equation (RMSE = 27.27, P = .004). Among subjects with cirrhosis and diuretic-refractory ascites, the accuracy of the equation we developed to estimate GFR (RMSE = 19.36) was greater than that of the CKD-EPI cystatin C (RMSE = 27.30, P = .003) and CKD-EPI creatinine-cystatin C equations (RMSE = 23.37, P = .004). CONCLUSIONS: We developed an equation that estimates GFR in subjects with cirrhosis and diuretic refractory ascites with greater accuracy than the CKD-EPI cystatin C equation or CKD-EPI creatinine-cystatin C equation. PMID- 26133904 TI - Uptake of Colon Capsule Endoscopy vs Colonoscopy for Screening Relatives of Patients With Colorectal Cancer. AB - BACKGROUND & AIMS: The efficacy of screening colonoscopy in first-degree relatives (FDRs) of patients with colorectal cancer (CRC) is limited by suboptimal uptake. We compared screening uptake of colon capsule endoscopy (CCE) vs colonoscopy in this population. METHODS: We performed a prospective study of 329 asymptomatic FDRs of patients with CRC who were randomly assigned to groups examined by CCE (PillCam, second generation; n = 165) or colonoscopy (n = 164) at a tertiary hospital in Spain from July 2012 through December 2013. Crossover was permitted for patients who did not wish to undergo the assigned procedure. Subjects assigned to CCE who had a significant lesion (polyp >= 10 mm, >2 polyps of any size, or CRC) were invited to undergo colonoscopy. RESULTS: One hundred twenty subjects in the CCE group and 113 in the colonoscopy group were eligible for inclusion. In the intention-to-screen analysis, uptake was similar between groups (55.8% CCE vs 52.2% colonoscopy; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.51-1.44; P = .57); 57.4% of subjects crossed over from the CCE group, and 30.2% crossed over from the colonoscopy group (OR, 3.11; 95% CI, 1.51 6.41; P = .002). Unwillingness to repeat bowel preparation in the case of a positive result was the main reason that subjects assigned to the CCE group crossed over; fear of colonoscopy was the reason that most patients in this group crossed over. A significant lesion was detected in 14 subjects (11.7%) in the CCE group and 13 subjects (11.5%) in the colonoscopy group (OR, 1.02; 95% CI, 0.45 2.26; P = .96). CONCLUSIONS: In a prospective study, similar numbers of FDRs of patients with CRC assigned to undergo CCE or colonoscopy agreed to participate, but most preferred to undergo colonoscopy. CCE was as effective as colonoscopy in detecting significant lesions; it could be a valid rescue strategy for subjects who reject screening colonoscopy. ClinicalTrials.gov number: NCT01557101. PMID- 26133905 TI - Abdominal Splenosis Mimicking a Liver Mass: Diagnosis by EUS-FNA. PMID- 26133906 TI - Vibrational modes of aminothiophenol: a TERS and DFT study. AB - We report Tip Enhanced Raman Spectroscopy (TERS) mapping and Density Functional (DFT) calculations of aminothiophenol (ATP) grafted on a gold surface. The TERS mapping has demonstrated Raman modes of (ATP) and its dimerised derivative Dimercaptoazobenzene (DMAB). This feature confirms that the plasmon activated chemical reaction of ATP has occurred during TERS measurements. In some specific part of the samples some unidentified Raman modes are observed. We suggest that they could come from intermediate species formed during the conversion of ATP into DMAB. These modes are compared with calculated Raman spectra of some possible intermediate species. These results confirm the high potentiality of TERS measurements for nanochemistry. PMID- 26133907 TI - The Surgical Management of Klatskin Tumours: Has Anything Changed in the Last Decade? AB - Surgical treatment of hilar cholangiocarcinomas requires complex pre-, intra- and post-operative decision-making. Despite the significant progress in liver surgery over the years, several issues such as the role of pre-operative biliary drainage, portal vein embolisation, staging laparoscopy and neo-adjuvant chemotherapy remain unresolved. Operative strategies such as vascular resection, caudate lobe resection and liver transplant have also been practiced in order to improve R0 resectability and improved survival. The review aims to consolidate evidence from major studies in the last 11 years. Survival data were only included from studies that reported the results in at least 30 patients with 1 year follow-up. A significant number of patients may be prevented an unnecessary laparotomy if they underwent a staging laparoscopy. There remain no guidelines as to when portal vein embolisation or pre-operative biliary drainage should be employed but most studies agree with pre-operative biliary drainage being an absolute indication if portal vein embolisation is performed. Concomitant hepatectomy and caudate lobectomy increases R0 resection but vascular resection cannot be routinely recommended. Liver transplant at specialised centres in selective patients has had impressive results. Guidelines are required for pre operative biliary drainage and portal vein embolisation and randomised trials are required in order to define the role of vascular resection in achieving a R0 resection and increasing survival. PMID- 26133908 TI - Pyogenic Liver Abscess: Does Escherichia Coli Cause more Adverse Outcomes than Klebsiella Pneumoniae? AB - BACKGROUND: This paper aims to demonstrate if Escherichia coli pyogenic liver abscess (ECPLA) results in adverse outcomes compared to Klebsiella pneumoniae PLA (KPPLA). METHODS: A retrospective review of all patients admitted at a tertiary hospital in Singapore from 2003 to 2011 was performed. Patients with age <18 years, amoebic liver abscess, infected liver cyst, culture negative abscess or ruptured liver abscess requiring urgent surgical intervention were excluded. Only patients with blood or pus culture confirmation of ECPLA (n = 24) or KPPLA (n = 264) were included. Median length of hospital stay, failure of non-operative therapy and 30-day mortality are the reported outcomes. RESULTS: ECPLA affects older patients (68 vs. 62 years, p = 0.049). Ischemic heart disease was more common in ECPLA (29 vs. 14 %, p = 0.048) and there was no difference in diabetic state (42 vs. 38 %, p = 0.743). ECPLA is more commonly associated with hyperbilirubinemia (60 vs. 34 umol/L, p = 0.003), increased gamma-glutamyl transpeptidase (236 vs. 16 IU/L, p = 0.038) and gallstones (58 vs. 30 %, p = 0.004). KPPLA are larger in size (6 vs. 4 cm, p = 0.006) and had percutaneous drainage (PD) more frequently (64 vs. 42 %, p = 0.034). There was no difference in median hospital stay (14 vs. 14 days, p = 0.110) or 30-day mortality (17 vs. 10 %, p = 0.307) between ECPLA and KPPLA. Among patients with ECPLA, antibiotic treatment with PD appeared to have higher mortality compared to antibiotic treatment alone (30 vs. 7 %) but this was not significant (p = 0.272). CONCLUSION: In the setting of multimodal care, outcomes of ECPLA are comparable to KPPLA. PMID- 26133909 TI - In Response to: Torsney KM, Cocker DM, Slesser AAP (2015) The Modern Surgeon and Competency Assessment: Are the Workplace-Based Assessments Evidence-Based? PMID- 26133910 TI - Single-Site Robotic Cholecystectomy: The Timeline of Progress. AB - AIM: To investigate the learning curve and perioperative outcomes of single-site robotic cholecystectomy during the first 102 cases by a single surgeon. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database was performed on the first 102 cases of single-site robotic cholecystectomy. Patients were divided into five chronological groups based on the date of surgery, with 20 patients in each group except the 5th group which had 22 patients. The groups were compared by docking time, robotic dissection time, and overall surgery time. A P value of 0.05 was used as statistically significant. RESULTS: The female to male ratio was 2:1. The mean age was 51 years (18-87) and the mean BMI was 28.26 (18-41). Overall, 69 % of the patients underwent elective cholecystectomy and 31 % required urgent surgery. In all, 17 % of patients had previous abdominal surgeries. In total, 45 % of procedures were regarded as same day surgery. The total mean length of stay was 1.97 days (0-8). The mean operative time was 110 min (36-265), mean robotic console time 70 min (26-179), and mean docking time 9 min (1-26). The overall conversion rate was 3.9 % and the complication rate was 4 %. The docking time, robotic time, and average operative time were significantly different in the first group as compared to the remaining the five groups (P = 0.001). CONCLUSION: Single-site robotic cholecystectomy is safe in both elective and urgent conditions, and in patients with previous abdominal surgeries. It has a short learning curve. PMID- 26133911 TI - Overexpression of heparan sulfate 6-O-sulfotransferase-2 enhances fibroblast growth factor-mediated chondrocyte growth and differentiation. AB - In our previous study, we reported that heparan sulfate 6-O-sulfotransferase-2 (HS6ST2) plays an important role in the cartilage of patients with osteoarthritis and Kashin-Beck disease and that it regulates aggrecan (Acan) metabolism and the viability of chondrocytes. However, its role in chondrocyte differentiation remains poorly understood. In the present study, we aimed to investigate the role of HS6ST2 in chondrocyte differentiation in vitro using mouse prechondrocytic cells. We found that the overexpression or silencing of HS6ST2 significantly enhanced or abrogated the effects of fibroblast growth factor (FGF)-2 on chondrocyte growth, respectively. We found that the overexpression of HS6ST2 significantly induced the expression of Acan as well as the amount of total proteoglycans in the prechondrocytic cells in the presence of FGF-2, whereas the silencing of HS6ST2 caused the opposite effect. Furthermore, the expresssion of FGF-2-induced sex-determining region Y-type high mobility group box protein 9 (SOX9), a major transcription factor for chondrocyte proliferation and differentiation, was also enhanced or blocked by HS6ST2 overexpression or HS6ST2 knockdown, respectively. Additionally, Wnt/beta-catenin signaling, which inhibited chondrocyte proliferation and differentiation, was suppressed by HS6ST2. Taken together, these data suggest that HS6ST2 plays an important role in regulating chondrocyte growth and differentiation by modulating FGF-2 signaling, thus indicating that it may be a potential and valuable molecular target for the treatment of skeletal dysplasias, such as dwarfism. PMID- 26133912 TI - Elastomeric Nanocomposite Foams for the Removal of Heavy Metal Ions from Water. AB - We report the fabrication and utilization of elastomeric polymer nanocomposite foams for the efficient removal of Pb2+ and Hg2+ heavy metal ions from polluted water. The polydimethylsiloxane (PDMS) foams are properly modified in order to become hydrophilic and allow the polluted water to penetrate in their volume. The ZnSe colloidal nanocrystals (NCs) that decorate the surface of the foams, act as active components able to entrap the metal ions. In this way, after the dipping of the nanocomposite foams in water polluted with Pb2+ or Hg2+, a cation exchange reaction takes place, and the heavy metal ions are successfully removed. The removal capacity for the Pb2+ ions exceeds 98% and the removal of Hg2+ ions approaches almost 100% in the studied concentrations region of 20-40 ppm. The reaction is concluded after 24 h, but it should be noticed that after the first hour, more than 95% of both the metal ions is removed. The color of the foams changes upon heavy metal ions entrapment, providing thus the opportunity of an easy detection of the presence of the ions in water. Taking into account that the fabricated foams provide good elastic properties and resistance to heat, they can be used in different conditions of water remediation. PMID- 26133914 TI - Ursodeoxycholic acid effectively kills drug-resistant gastric cancer cells through induction of autophagic death. AB - Carcinoma cells that have acquired drug resistance often exhibit cross-resistance to various other cytotoxic stimuli. Here, we investigated the effects of ursodeoxycholic acid (UDCA), a gastrointestinal tumor-suppressor, on a cisplatin resistant SNU601 gastric cancer subline (SNU601/R). While other anticancer drugs, including L-OHP, etoposide, and death ligand TRAIL, had minimal effects on the viability of these resistant cells, they were sensitive to UDCA. The UDCA-induced reduction in the viability of the SNU601/R cells was accomplished through autophagy while the primary means of cell death in the parental SNU601 cells (SNU601/WT) was apoptosis. Previously, we demonstrated that the UDCA-triggered apoptosis of gastric cancer cells was regulated by a cell surface death receptor, TRAIL-R2/DR5, which was upregulated and re-distributed on lipid rafts. The UDCA stimulation of TRAIL-R2/DR5 also occurred in the SNU601/R cells despite the lack of apoptosis. In the present study, we found that CD95/Fas, another cell surface death receptor, was also translocated into lipid rafts in response to UDCA although it was not involved in the decrease in cell viability. Specifically, raft relocalization of CD95/Fas was triggered by UDCA in the SNU601/WT cells in which apoptosis occurred, but not in the SNU601/R cells where autophagic death occurred. Notably, UDCA reduced ATG5 levels, an essential component of autophagy, in the SNU601/WT, but not in the SNU601/R cell line. Moreover, in CD95/Fas silenced SNU601/WT cells, UDCA did not decrease ATG5 levels and induced autophagic cell death rather than apoptosis. These results imply that raft distributed CD95/Fas may support UDCA-induced apoptosis via downregulation of ATG5 levels, preventing the autophagic pathway. Taken together, these results suggest that UDCA induces both apoptotic and autophagic cell death depending on the intracellular signaling environment, thereby conferring the advantage to overcome drug resistance through apoptotic defects. PMID- 26133913 TI - Patterns of Care for Localized Breast Cancer in Oklahoma, 2003-2006. AB - Despite well-established clinical guidelines for breast cancer treatment, Standard of Care (SOC) is not universal in the U.S. The purpose of this study was to describe the extent to which patients receive guideline-based, stage-specific treatments for localized female breast cancer in Oklahoma. Data were obtained from the Oklahoma Central Cancer Registry for the period 2003-2006. We included localized, invasive female breast cancers and analyzed both treatment and demographic factors. We used the National Comprehensive Cancer Network (NCCN) treatment guidelines to determine SOC. Among women who received breast conserving surgery (BCS), we used logistic regression to evaluate factors related to SOC. In Oklahoma, 92 percent of the 4,177 localized breast cancer patients were treated with recognized SOC. In women aged >=65 years with BCS, those >=75 years had a lower adjusted odds of meeting SOC than did those without insurance, with comorbid conditions, or whose comorbid status was unknown. Among women aged <65 years, those with Medicare/Medicaid, Medicare only, or without insurance, along with comorbid conditions, had a lower adjusted odds of meeting SOC. Overall, 92 percent of women met SOC. Factors such as age, insurance type, and comorbid conditions were associated with meeting SOC. PMID- 26133915 TI - What's God Got to Do with It? How Religiosity Predicts Atheists' Health. AB - The relationship between atheism and health is poorly understood within the Religion/Spirituality-health literature. While the extant literature promotes the idea that Attendance, Prayer, and Religiosity are connected to positive health outcomes, these relationships have not been established when controlling for whether a person is an atheist. Data from the 2008-2012 American General Social Survey (n = 3210) were used to investigate this relationship. Results indicated that atheists experienced Religiosity more negatively than non-atheists. Additionally, results demonstrated that non-belief in God was not related to better or worse perceived global health, suggesting that belief in God is not inherently linked to better reported health. PMID- 26133916 TI - Rapid review: sinonasal surgery vs. medical therapy for asthma in patients with chronic rhinosinusitis with or without nasal polyps. AB - The objective of the study was to compare the effect of sinonasal surgery vs. medical treatment on asthma in patients with chronic rhinosinusitis with or without nasal polyps. We executed a PRISMA guidelines-based systematic search of the following databases: PubMed, CENTRAL, Embase, Scopus and CINAHL. The search ran from database inception until 26 Feb 2014. We included controlled clinical trials comparing surgical intervention with medical intervention in patients with chronic rhinosinusitis with or without nasal polyps. We included only English papers. We used a pre-defined data collection form. Two authors independently assessed study quality. We assessed directness of evidence and risk of bias using pre-defined criteria. Our search yielded 2004 original articles, six of which satisfied our inclusion criteria. One article was excluded from further review because no comparison could be made of the subgroup of operated asthmatic patients versus the non-surgical control group. Only one study used objective pulmonary function measurements in asthmatics undergoing sinonasal surgery and therefore had the highest directness of evidence. Also it had a low risk of bias. Patient characteristics, treatments and outcome measures varied across studies, as did the observed effect. Risk of bias was high in most studies. Patient characteristics, treatment and outcome measurement differed across studies, making a comparison of the effects difficult. There is a risk of publication language bias. There is insufficient evidence either for or against sinonasal surgery for asthma control as compared to medical treatment. PMID- 26133917 TI - Erratum to: Open questions and novel concepts in oral cancer surgery. PMID- 26133918 TI - Re: Tumor size measured by preoperative ultrasonography and postoperative pathologic examination in papillary thyroid carcinoma: relative differences according to size, calcification and coexisting thyroiditis. PMID- 26133919 TI - The effects of bone pate on human osteoblasts cell cultures. AB - The aim of the present study was to evaluate the effect of bone pate on human osteoblast differentiation by measuring cell viability, alkaline phosphatase activity and expression of the transcription factors and of the major components of the extracellular matrix. Although bone pate has been used in ear surgery for many years and when placed in contact with mastoid and external auditory canal bone become viable, the cellular mechanisms that lead to its osteointegration have never been described. Bone pate taken from four patients subjected to mastoidectomy and affected by middle ear and mastoid cholesteatoma was placed in contact with osteoblast-like cell cultures. Four experimental conditions were obtained: cell cultures treated with bone pate, with bone pate mixed with fibrin glue, with fibrin glue and untreated. After 24 h, the viability of the cells was evaluated; after 1 week, alkaline phosphatase activity and the expression of transcription factors and bone matrix proteins were assessed by quantitative polymerase chain reaction. After 24 h osteoblasts showed increased viability when treated with bone pate (19 % increase) and bone pate mixed with fibrin glue (34 % increase). After 1 week, the number of alkaline phosphatase positive cells increased by 97 and 94 % in cultures treated with bone pate alone and bone pate mixed with fibrin glue. Treatment with bone pate upregulated transcription factors and components of the extracellular matrix. The present data show that bone pate has a high osteoinductive potential on human osteoblasts, enhancing their activity. PMID- 26133920 TI - A Sex Disparity Among Earthquake Victims. AB - OBJECTIVE: Understanding who is most vulnerable during an earthquake will help health care responders prepare for future disasters. We analyzed the demography of casualties from the Christchurch earthquake in New Zealand. METHODS: The demography of the total deceased, injured, and hospitalized casualties of the Christchurch earthquake was compared with that of the greater Christchurch population, the Christchurch central business district working population, and patients who presented to the single acute emergency department on the same month and day over the prior 10 years. Sex data were compared to scene of injury, context of injury, clinical characteristics of injury, and injury severity scores. RESULTS: Significantly more females than males were injured or killed in the entire population of casualties (P20% were injured at commercial or service localities (444/2032 males [22%]; 1105/4627 females [24%]). Adults aged between 20 and 69 years (1639/2032 males [81%]; 3717/4627 females [80%]) were most frequently injured. CONCLUSION: Where people were and what they were doing at the time of the earthquake influenced their risk of injury. PMID- 26133921 TI - Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer. AB - Resistance to aromatase inhibitors (AIs) involves increased HER2. One mechanism by which HER2 may mediate resistance is through expansion of the tumor initiating cell (TIC) population. This study investigates whether combining all-trans retinoic acid (ATRA) and histone deacetylase inhibitor entinostat (ENT) can inhibit TICs and HER2 in AI-resistant cells and tumors. Modulation of cell viability and HER2 expression were assessed in AI-resistant cells treated with ATRA + ENT. Letrozole-resistant LTLT-Ca cells treated with ATRA + ENT were assayed for changes in TIC characteristics, such as TIC markers (BCRP, ALDH, and BMI-1), side population (SP), and mammosphere formation. Xenograft tumors of MCF 7Ca cells made resistant to letrozole were treated with ATRA, ATRA + letrozole, ATRA + ENT, or ATRA + ENT + letrozole. Resulting tumors were assayed for changes in TIC characteristics. Patient samples taken pre- and post-AI treatment were analyzed for changes in ERalpha and HER2 protein expression. Treatment with ATRA + ENT reduced HER2 expression and viability (P < 0.001) in AI-resistant cells, as well as decreased SP (P < 0.0001), mammosphere formation (P < 0.01), and expression of TIC molecular markers (P < 0.01) in LTLT-Ca. A reduction in tumor growth rate was observed in mice treated with ENT + ATRA + letrozole when compared to mice treated with single agents (P < 0.0001) or ENT + ATRA (P = 0.02). Decreased TIC characteristics, including mammosphere formation (P < 0.05), were observed in tumors from the triple combination. An increase in HER2 and downregulation in ERalpha protein expression was observed in patients upon resistance to AI (P < 0.005). These studies indicate that the combination of ATRA and ENT inhibits the TIC population of AI-resistant cells and may be effective in reducing tumor recurrence. PMID- 26133923 TI - Pilates for low back pain. AB - BACKGROUND: Non-specific low back pain is a major health problem worldwide. Interventions based on exercises have been the most commonly used treatments for patients with this condition. Over the past few years, the Pilates method has been one of the most popular exercise programmes used in clinical practice. OBJECTIVES: To determine the effects of the Pilates method for patients with non specific acute, subacute or chronic low back pain. SEARCH METHODS: We conducted the searches in CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro and SPORTDiscus from the date of their inception to March 2014. We updated the search in June 2015 but these results have not yet been incorporated. We also searched the reference lists of eligible papers as well as six trial registry websites. We placed no limitations on language or date of publication. SELECTION CRITERIA: We only included randomised controlled trials that examined the effectiveness of Pilates intervention in adults with acute, subacute or chronic non-specific low back pain. The primary outcomes considered were pain, disability, global impression of recovery and quality of life. DATA COLLECTION AND ANALYSIS: Two independent raters performed the assessment of risk of bias in the included studies using the 'Risk of bias' assessment tool recommended by The Cochrane Collaboration. We also assessed clinical relevance by scoring five questions related to this domain as 'yes', 'no' or 'unclear'. We evaluated the overall quality of evidence using the GRADE approach and for effect sizes we used three levels: small (mean difference (MD) < 10% of the scale), medium (MD 10% to 20% of the scale) or large (MD > 20% of the scale). We converted outcome measures to a common 0 to 100 scale when different scales were used. MAIN RESULTS: The search retrieved 126 trials; 10 fulfilled the inclusion criteria and we included them in the review (a total sample of 510 participants). Seven studies were considered to have low risk of bias, and three were considered as high risk of bias.A total of six trials compared Pilates to minimal intervention. There is low quality evidence that Pilates reduces pain compared with minimal intervention, with a medium effect size at short-term follow-up (less than three months after randomisation) (MD 14.05, 95% confidence interval (CI) -18.91 to -9.19). For intermediate-term follow-up (at least three months but less than 12 months after randomisation), two trials provided moderate quality evidence that Pilates reduces pain compared to minimal intervention, with a medium effect size (MD -10.54, 95% CI -18.46 to 2.62). Based on five trials, there is low quality evidence that Pilates improves disability compared with minimal intervention, with a small effect size at short term follow-up (MD -7.95, 95% CI -13.23 to -2.67), and moderate quality evidence for an intermediate-term effect with a medium effect size (MD -11.17, 95% CI 18.41 to -3.92). Based on one trial and low quality evidence, a significant short term effect with a small effect size was reported for function (MD 1.10, 95% CI 0.23 to 1.97) and global impression of recovery (MD 1.50, 95% CI 0.70 to 2.30), but not at intermediate-term follow-up for either outcome.Four trials compared Pilates to other exercises. For the outcome pain, we presented the results as a narrative synthesis due to the high level of heterogeneity. At short-term follow up, based on low quality evidence, two trials demonstrated a significant effect in favour of Pilates and one trial did not find a significant difference. At intermediate-term follow-up, based on low quality evidence, one trial reported a significant effect in favour of Pilates, and one trial reported a non-significant difference for this comparison. For disability, there is moderate quality evidence that there is no significant difference between Pilates and other exercise either in the short term (MD -3.29, 95% CI -6.82 to 0.24) or in the intermediate term (MD -0.91, 95% CI -5.02 to 3.20) based on two studies for each comparison. Based on low quality evidence and one trial, there was no significant difference in function between Pilates and other exercises at short-term follow up (MD 0.10, 95% CI -2.44 to 2.64), but there was a significant effect in favour of other exercises for intermediate-term function, with a small effect size (MD 3.60, 95% CI -7.00 to -0.20). Global impression of recovery was not assessed in this comparison and none of the trials included quality of life outcomes. Two trials assessed adverse events in this review, one did not find any adverse events, and another reported minor events. AUTHORS' CONCLUSIONS: We did not find any high quality evidence for any of the treatment comparisons, outcomes or follow-up periods investigated. However, there is low to moderate quality evidence that Pilates is more effective than minimal intervention for pain and disability. When Pilates was compared with other exercises we found a small effect for function at intermediate-term follow-up. Thus, while there is some evidence for the effectiveness of Pilates for low back pain, there is no conclusive evidence that it is superior to other forms of exercises. The decision to use Pilates for low back pain may be based on the patient's or care provider's preferences, and costs. PMID- 26133924 TI - Ca(II) -catalyzed alkenylation of alcohols with vinylboronic acids. AB - Direct alkenylation of a variety of alcohols with vinylboronic acids has been accomplished using the air-stable calcium(II) complex Ca(NTf2 )2 under mild conditions with short reaction times. For reluctant transformations, an ammonium salt was used as an additive to circumvent the reactivity issue. PMID- 26133925 TI - Family Ratings of Communication Largely Reflect Expressive Language and Conversation-Level Ability in People With Aphasia. AB - PURPOSE: Family ratings of communication and social interactions represent an important source of information about people with aphasia. Because of the reliance on family/partner ratings as an outcome measure in many aphasia treatment studies and in the clinic, there is a great need for the validation of commonly used family/partner rating measures, and a better understanding of predictors of family ratings of communication. METHOD: The communication ability of 130 individuals with aphasia due to neurologic illness was rated by family members/partners on the Communicative Effectiveness Index (CETI; Lomas et al., 1989). Information on aphasia severity, mood, quality of life, nonverbal cognitive functioning, and various demographic factors was collected. RESULTS: Principal component analysis confirmed a 2-factor model best represents the relationships among CETI rating items, and this model largely consists of a conversation-level ability factor. Family ratings were largely predicted by the patient's expressive (not receptive) language but also patient self-perceived quality of communication life. CONCLUSIONS: Family/partners typically rate the effectiveness of communication based largely on expressive language, despite the fact that other aspects of the aphasia (e.g., listening comprehension) are as important for everyday communication. PMID- 26133926 TI - Complete genome sequence of Bifidobacterium pseudocatenulatum JCM 1200(T) isolated from infant feces. AB - Bifidobacterium pseudocatenulatum JCM 1200(T) was isolated from infant feces. This paper is the first report demonstrating the fully sequenced and completely annotated genome of a B. pseudocatenulatum strain. PMID- 26133927 TI - Complete genome sequence of Bifidobacterium bifidum JCM 1255(T) isolated from feces of a breast-fed infant. AB - Bifidobacterium bifidum JCM 1255(T) was isolated from feces of a breast-fed infant. Here we report the complete genome sequence of this organism. PMID- 26133928 TI - Comparing effects of perfusion and hydrostatic pressure on gene profiles of human chondrocyte. AB - Hydrostatic pressure and perfusion have been shown to regulate the chondrogenic potential of articular chondrocytes. In order to compare the effects of hydrostatic pressure plus perfusion (HPP) and perfusion (P) we investigated the complete gene expression profiles of human chondrocytes under HPP and P. A simplified bioreactor was constructed to apply loading (0.1 MPa for 2 h) and perfusion (2 ml) through the same piping by pressurizing the medium directly. High-density monolayer cultures of human chondrocytes were exposed to HPP or P for 4 days. Controls (C) were maintained in static cultures. Gene expression was evaluated by sequencing (RNAseq) and quantitative real-time PCR analysis. Both treatments changed gene expression levels of human chondrocytes significantly. Specifically, HPP and P increased COL2A1 expression and decreased COL1A1 and MMP 13 expression. Despite of these similarities, RNAseq revealed a list of cartilage genes including ACAN, ITGA10 and TNC, which were differentially expressed by HPP and P. Of these candidates, adhesion related molecules were found to be upregulated in HPP. Both HPP and P treatment had beneficial effects on chondrocyte differentiation and decreased catabolic enzyme expression. The study provides new insight into how hydrostatic pressure and perfusion enhance cartilage differentiation and inhibit catabolic effects. PMID- 26133929 TI - Complete genome sequence of Lactobacillus salivarius Ren, a probiotic strain with anti-tumor activity. AB - Lactobacillus salivarius Ren (LsR) (CGMCC No. 3606) is a probiotic strain that was isolated from the feces of a healthy centenarian living in Bama, Guangxi, China. Previous studies have shown that this strain decreases 4-nitroquinoline 1 oxide (4-NQO)-induced genotoxicity in vitro. It also suppresses 4-NQO-induced oral carcinogenesis and 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis, and therefore may be used as an adjuvant therapeutic agent for cancer. Here, we report the complete genome sequence of LsR that consists of a circular chromosome of 1751,565 bp and two plasmids (pR1, 176,951 bp; pR2, 49,848 bp). PMID- 26133931 TI - Analysis of linear viscoelastic behaviour of alginate gels: effects of inner relaxation, water diffusion, and syneresis. AB - The mechanical behaviour of ionically cross-linked alginate gels is investigated here in detail. To determine the range of linear response of the materials, uniaxial, unconfined compression and torsional deformation experiments are performed, obtaining both the stress-strain and the viscoelastic behaviour of the gels. On-line measurements of the radii of the cylindrical gel samples in these experiments are also reported. The linearity range in the gel mechanical response is found to be rather limited, up to 6% strain, at most, contrary to more optimistic conclusions usually reported in the literature. We confirm the presence of a stress-diffusion coupling phenomenon in our alginates, i.e., the migration of water from/into the gels in response to the applied deformation. A phenomenon of inner (constitutive) relaxation of the network component of the gels is also clearly identified, and observed to occur, in parallel with solvent diffusion, upon compression. At sufficiently longer times after a deformation step, syneresis is always observed, with concomitant nonstandard viscoelastic effects, such as the growth of a normal force in torsion, and a size dependent decay of the longitudinal force in compression. We applied a two-fluid model, recently developed by two of the present authors [D. Larobina and F. Greco, J. Chem. Phys., 2012, 136(13), 134904], to simulate the relaxation tests upon torsional and compressive deformations, and to fit our own experiments. The model is found to well describe the coupling between constitutive relaxation and diffusion, and to reproduce the available force and radii data before the advent of syneresis. PMID- 26133930 TI - Complete genome sequence of Bifidobacterium catenulatum JCM 1194(T) isolated from human feces. AB - Bifidobacterium catenulatum JCM 1194(T) was isolated from human feces. This paper is the first report demonstrating the fully sequenced and completely annotated genome of a B. catenulatum strain. PMID- 26133932 TI - Relations between youths' conceptions of spirituality and their developmental outcomes. AB - This study uses a positive youth development (PYD) approach to explore whether differences in youths' conceptions of spirituality were linked to patters of difference regarding 6 domains of PYD. Using data from the 4-H Study of Positive Youth Development, findings revealed a consistent trend across 6 domains of positive development. Youth who had coherent conceptions of being spiritual generally scored highest on measures of positive development, whereas youth in the ambiguous spirituality group (i.e., less coherent) scored the lowest. However, follow-up analyses reveal that such relations did not hold over time. Implications of findings include youth development professionals aiming to nurture the spiritual growth of youth should encourage more coherent notions of spirituality among the youth they serve. PMID- 26133933 TI - The Effects of Near-Infrared Spectroscopy on the Neurocognitive Functions in the Patients Undergoing Coronary Artery Bypass Grafting with Asymptomatic Carotid Artery Disease: A Randomized Prospective Study. AB - PURPOSE: The purpose of this study was to research the use of near-infrared spectroscopy (NIRS) on the neurocognitive functions in the patients undergoing coronary artery bypass grafting (CABG) with asymptomatic carotid artery disease. METHODS: The study design was carried out with the participation of 79 patients in a prospective, randomized and double blind control method. The patients were separated into two groups as NIRS (n = 43) and no NIRS (n = 36). A neurocognitive test was applied preoperatively and postoperatively to all patients before discharge. Cognitive functions were evaluated by applying the Montreal Cognitive Assessment test (MoCA). RESULTS: The decrease in the postoperative score of mean MoCA in no NIRS group was statistically significant when compared to preoperatively (p <0.001). Postoperative mean MoCA score was found to be significantly higher in NIRS group (NIRS: 26.8 +/- 1.9 vs. no NIRS: 23.6 +/- 2.5, p <0.001). It has been determined that there was a moderately positive significant correlation between the increase in the NIRS used patients (%) and increase in the MoCA score of the patients (r = 0.59, p <0.001). CONCLUSION: Intraoperative NIRS usage in the patients undergoing CABG with carotid artery disease might be useful due to its postoperative positive effects on the cognitive functions. PMID- 26133934 TI - Quantitative analysis of 3-dimensional facial soft tissue photographic images: technical methods and clinical application. AB - BACKGROUND: The recent advent of 3D photography has created the potential for comprehensive facial evaluation. However, lack of practical true 3D analysis of the information collected from 3D images has been the factor limiting widespread utilization in orthodontics. Current evaluation of 3D facial soft tissue images relies on subjective visual evaluation and 2D distances to assess facial disharmony. The objectives of this project strive to map the surface and define boundaries of 3D facial soft tissue, modify mathematical functions to average multiple 3D facial images, and mathematically average 3D facial images allowing generation of color-coded surface deviation relative to a true average. METHODS: Collaboration headed by UCLA Orthodontics with UCLA Neuroimaging was initiated to modify advanced brain mapping technology to accurately map the facial surface in 3D. 10 subjects were selected as a sample for development of the technical protocol. 3dMD photographic images were segmented, corrected using a series of topology correcting algorithms, and process to create close meshes. Shapes were mapped to a sphere using conformal and area preserving maps, and were then registered using a spherical patch mapping approach. Finally an average was created using 7-parameter procrustes alignment. RESULTS: Size-standardized average facial images were generated for the sample population. A single patient was then superimposed on the average and color-coded displacement maps were generated to demonstrate the clinical applicability of this protocol. Further confirmation of the methods through 3D superimposition of the initial (T0) average to the 4 week (T4) average was completed and analyzed. CONCLUSIONS: The results of this investigation suggest that it is possible to average multiple facial images of highly variable topology. The immediate application of this research will be rapid and detailed diagnostic imaging analysis for orthodontic and surgical treatment planning. There is great potential for application to anthropometrics and genomics. This investigation resulted in establishment of a protocol for mapping the surface of the human face in three dimensions. PMID- 26133936 TI - Extracellular and Intracellular Signaling for Neuronal Polarity. AB - Neurons are one of the highly polarized cells in the body. One of the fundamental issues in neuroscience is how neurons establish their polarity; therefore, this issue fascinates many scientists. Cultured neurons are useful tools for analyzing the mechanisms of neuronal polarization, and indeed, most of the molecules important in their polarization were identified using culture systems. However, we now know that the process of neuronal polarization in vivo differs in some respects from that in cultured neurons. One of the major differences is their surrounding microenvironment; neurons in vivo can be influenced by extrinsic factors from the microenvironment. Therefore, a major question remains: How are neurons polarized in vivo? Here, we begin by reviewing the process of neuronal polarization in culture conditions and in vivo. We also survey the molecular mechanisms underlying neuronal polarization. Finally, we introduce the theoretical basis of neuronal polarization and the possible involvement of neuronal polarity in disease and traumatic brain injury. PMID- 26133938 TI - Utility of immunophenotyping of plasma cells in multiple myeloma. PMID- 26133939 TI - Urinary retinol binding protein is a potential biomarker for renal function in primary systemic amyloidosis: A retrospective study. PMID- 26133940 TI - A new piece to the stereotypy "puzzle" in chronic lymphocytic leukemia. PMID- 26133941 TI - Chemical shift assignments of a new folded domain from yeast Pcf11. AB - The yeast protein Pcf11 is a component of the cleavage/polyadenylation factor IA (CF IA) complex involved in the 3' processing of pre-mRNA. Pcf11 interacts with RNA and the C-terminal domain (CTD) of the largest subunit of RNA polymerase II via the CTD-interaction domain (CID), and other peptide regions mediate contacts with CF IA subunits Clp1 and Rna14/Rna15. We have identified a novel domain adjacent to the CID and have determined the backbone and sidechain (1)H, (13)C and (15)N chemical shift assignments for the bacterially produced construct. Despite the reduced sequence complexity due to numerous glutamine and leucine residues, secondary chemical shift analysis indicates that the domain is composed of three well-defined helical regions with relaxation measurements consistent with a folded independent domain. The proximity of this previously uncharacterized domain close to the N-terminal CID prompts speculation for a putative role in modulating CTD and RNA binding, or possible intermolecular contacts within CF IA. PMID- 26133942 TI - Divergent Patterns of Incidence in Peripheral Neuroblastic Tumors. AB - BACKGROUND: Prior research on trends in neuroblastoma incidence has conflicted. We aimed to compare how ganglioneuroblastoma and neuroblastoma incidence have changed. PROCEDURE: Using the Surveillance Epidemiology and End Results (SEER) 9 population-based registry, we identified 2081 malignant peripheral neuroblastic tumors in patients 0 to 14 years from 1973 to 2009. Age-adjusted annual incidence rates were calculated using SEER*Stat, and Joinpoint Regression Program was used to calculate annual percent change (APC) and analyze trends. Data were stratified by histology, age, and stage. RESULTS: Overall peripheral neuroblastic tumor incidence increased by an APC of 0.47 (P=0.045). However, ganglioneuroblastoma incidence decreased (APC=-1.48; P=0.003), whereas neuroblastoma incidence increased (APC=0.79; P=0.008). When divided by age and stage, locoregional neuroblastoma incidence increased in infants until a significant inflection point in 1996 (APC=4.19; P<0.001) and then decreased sharply (APC=-6.80; P=0.160). CONCLUSIONS: Ganglioneuroblastoma incidence has decreased, whereas neuroblastoma incidence has increased. These changes could be real, or reflect bias from classification changes or increased detection. Neuroblastoma incidence increased most markedly in infants with locoregional disease only until 1996, then declined, which may reflect changes in tumor ascertainment and folate supplementation. PMID- 26133943 TI - Erratum to: A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control. PMID- 26133935 TI - Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature. AB - Spreading depression (SD) is a transient wave of near-complete neuronal and glial depolarization associated with massive transmembrane ionic and water shifts. It is evolutionarily conserved in the central nervous systems of a wide variety of species from locust to human. The depolarization spreads slowly at a rate of only millimeters per minute by way of grey matter contiguity, irrespective of functional or vascular divisions, and lasts up to a minute in otherwise normal tissue. As such, SD is a radically different breed of electrophysiological activity compared with everyday neural activity, such as action potentials and synaptic transmission. Seventy years after its discovery by Leao, the mechanisms of SD and its profound metabolic and hemodynamic effects are still debated. What we did learn of consequence, however, is that SD plays a central role in the pathophysiology of a number of diseases including migraine, ischemic stroke, intracranial hemorrhage, and traumatic brain injury. An intriguing overlap among them is that they are all neurovascular disorders. Therefore, the interplay between neurons and vascular elements is critical for our understanding of the impact of this homeostatic breakdown in patients. The challenges of translating experimental data into human pathophysiology notwithstanding, this review provides a detailed account of bidirectional interactions between brain parenchyma and the cerebral vasculature during SD and puts this in the context of neurovascular diseases. PMID- 26133944 TI - Comparison of the effects of sodium hyaluronate-chondroitin sulphate and corticosteroid in the treatment of lateral epicondylitis: a prospective randomized trial. AB - BACKGROUND: Hyaluronic acid and glycosaminoglycans have shown positive effects in improving lateral epicondylitis and other tendinosis conditions. Therefore, we designed a prospective, randomized study to compare the effects of a combined sodium hyaluronate and chondroitin sulfate (HA + CS) injection versus a triamcinolone injection in the treatment of lateral epicondylitis. METHODS: In total, 57 consecutive patients with clinically diagnosed lateral epicondylitis were divided randomly into two groups. In the HA + CS group, 25 patients received a single injection of a solution containing an HA + CS combination and prilocaine HCl, while the 32 patients in the triamcinolone group received a single injection of a solution of triamcinolone and prilocaine HCl. We evaluated the pain and function outcome measures using the Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaire at the beginning of the study, and 3 and 6 months after the injection. Additionally, the Minimum Clinically Important Difference values and percentage changes in the PRTEE subscale scores between the assessments were calculated. RESULTS: No serious adverse events were reported throughout the study. The mean pain and function scores for the HA + CS and triamcinolone groups had significantly improved at 3 months, but the mean function scores in the HA + CS group were statistically significantly better when compared to the triamcinolone group. At 6 months, both groups had significantly improved mean pain and function scores, compared to the baseline scores; however, the mean pain and function scores in the 6-month HA + CS treatment group were better than in the 6-month triamcinolone group. The relative change for the mean total score in the HA + CS group was much better when compared with the triamcinolone group, and the HA + CS treatment group showed clinically significant improvement when compared with triamcinolone group at 3 and 6 months. CONCLUSIONS: This study supports the idea that for a single injection treatment of patients with lateral epicondylitis, a combination injection of HA + CS may offer better pain benefits for 6 months after injection, when compared to triamcinolone. TYPE OF STUDY/LEVEL OF EVIDENCE: Level II, Randomized Clinical Trial, Prospective Comparative Study. PMID- 26133945 TI - Solution-Dispersible Metal Nanorings with Deliberately Controllable Compositions and Architectural Parameters for Tunable Plasmonic Response. AB - We report a template-based technique for the preparation of solution-dispersible nanorings composed of Au, Ag, Pt, Ni, and Pd with control over outer diameter (60 400 nm), inner diameter (25-230 nm), and height (40 nm to a few microns). Systematic and independent control of these parameters enables fine-tuning of the three characteristic localized surface plasmon resonance modes of Au nanorings and the resulting solution-based extinction spectra from the visible to the near infrared. This synthetic approach provides a new pathway for solution-based investigations of surfaces with negative curvature. PMID- 26133946 TI - The direct effect of exposure to disease in early life on the height of young adult men in southern Sweden, 1814-1948. AB - This paper considers whether short-term variation in exposure to disease early in life, as measured by a variety of mortality rates, has an effect on the height of young adults. Height information for men born in southern Sweden, 1814-1948, and included in the Scanian Economic Demographic Database (SEDD), was obtained from records of medical inspections carried out as part of Sweden's system of universal conscription. Community-level infant mortality rates were calculated not only by year of birth but also for time in utero and in the first year of life. Comparison between brothers was used to remove the influence of confounding factors. The results suggest that any effect that exposure to disease in early life, as measured by mortality rates, may have had on height, either through selection or scarring, is likely to have been very weak. Supplementary material for this article is available at: http://dx.doi.org/10.1080/00324728.2015.1045545. PMID- 26133947 TI - Congenital methemoglobinemia type 2 and cerebellar atrophy/hypoplasia. PMID- 26133948 TI - Role of admission serum albumin levels in patients with intracerebral hemorrhage. AB - Low serum albumin levels have been reported to be an independent predictor of increased morbidity and mortality in multiple disease conditions. The aim of our study was to identify the impact of low serum albumin levels on mortality and outcomes at discharge in patients with intracerebral hemorrhage. We retrospectively reviewed our prospective database of patients with intracerebral hemorrhage from January 2010 to December 2011. Patients were dichotomized into two groups based on their serum albumin levels upon admission. Hypoalbuminemia was defined as serum albumin levels <=3.4 g/dl. The two groups were compared using Fisher's exact test for categorical variables and t test for continuous variables. Poor outcome was defined as death or discharge to a long-term nursing facility (modified Rankin Score 4-6). Out of 97 patients admitted with intracerebral hemorrhage, 90 met our inclusion criteria (42 had normal levels and 48 had hypoalbuminemia). The baseline characteristics, risk factors, etiology, location and volume of intracerebral hemorrhage, admission blood glucose, white cell count, length of hospital stay, length of intensive care unit stay, and complications were similar between both groups. Although admission hypoalbuminemia did not impact in-hospital mortality (28 vs 24 %, p = 0.635), there was a significant increase in poor outcomes at discharge (59 vs 31 %, p = 0.009) (OR 1.8; 95 % CI; 1.2-2.8). Similar to other diseases, hypoalbuminemia was associated with poor functional outcomes in patients with intracerebral hemorrhage. This will need to be confirmed in larger prospective studies before adopting therapeutic and preventive strategies in future. PMID- 26133949 TI - Percheron artery infarction in the differential diagnosis of acute confusional state with normal initial brain MRI. PMID- 26133950 TI - An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice. AB - Cancer cachexia is characterized by muscle wasting caused partly by systemic inflammation. We previously demonstrated an immune-modulating diet (IMD), an enteral diet enriched with immunonutrition and whey-hydrolyzed peptides, to have antiinflammatory effects in some experimental models. Here, we investigated whether the IMD in combination with chemotherapy could prevent cancer cachexia in colon 26 tumor-bearing mice. Forty tumor-bearing mice were randomized into 5 groups: tumor-bearing control (TB), low dose 5-fluorouracil (5-FU) and standard diet (LF/ST), low dose 5-FU and IMD (LF/IMD), high dose 5-FU and standard diet (HF/ST) and high dose 5-FU and IMD (HF/IMD). The ST and IMD mice received a standard diet or the IMD ad libitum for 21 days. Muscle mass in the IMD mice was significantly higher than that in the ST mice. The LF/IMD in addition to the HF/ST and HF/IMD mice preserved their body and carcass weights. Plasma prostaglandin E2 levels were significantly lower in the IMD mice than in the ST mice. A combined effect was also observed in plasma interleukin-6, glucose, and vascular endothelial growth factor levels. Tumor weight was not affected by different diets. In conclusion, the IMD in combination with chemotherapy prevented cancer cachexia without suppressing chemotherapeutic efficacy. PMID- 26133951 TI - Correction: Controllable poly-crystalline bilayered and multilayered graphene film growth by reciprocal chemical vapor deposition. AB - Correction for 'Controllable poly-crystalline bilayered and multilayered graphene film growth by reciprocal chemical vapor deposition' by Qinke Wu et al., Nanoscale, 2015, 7, 10357-10361. PMID- 26133952 TI - Unforgiveness, depression, and health in later life: the protective factor of forgivingness. AB - OBJECTIVES: Feeling unforgiven by others has been linked to poor health outcomes. The current study examined whether feeling unforgiven by others is associated with depression and self-rated health among older adults in the United States. The potential moderating roles of forgiving others and self-forgiveness in the association between unforgiveness and both depression and self-rated health was also assessed along with gender differences. METHOD: Data were drawn from a sample of 1009 adults in Wave 2 of the Religion, Aging, and Health Survey, a national sample of adults aged over 67. Depression was measured using the eight item short form from the Center for Epidemiologic Studies-Depression (CES-D) scale. Self-rated health was assessed with a one-item indicator. RESULTS: Analyses indicated that higher levels of self-forgiveness ameliorated the relationship between unforgiveness by others and depression for men and women and higher levels of forgiving others attenuated the association between unforgiveness by others and depression for women. Self-forgiveness was protective of depression for women who reported unforgiveness by others and low levels of forgiving others. Regardless of levels of self-forgiveness, men who were most likely to forgive others experienced a significant association between unforgiveness by others and depression. Neither forgiving others nor the self were significant moderators in the association between unforgiveness and self rated health. CONCLUSION: Forgiving others and the self may be protective of well being when women feel unforgiven by others. These findings have implications for forgiveness intervention programs and contribute to literature pertaining to forgiveness and health in later life. PMID- 26133959 TI - Photodynamic inactivation induced by carboxypterin: a novel non-toxic bactericidal strategy against planktonic cells and biofilms of Staphylococcus aureus. AB - Microbial related contamination is of major concern and can cause substantial economic losses. Photodynamic inactivation (PDI) has emerged as a suitable approach to inhibit microorganism proliferation. In this work, PDI induced by 6 carboxypterin (Cap), a biocompatible photosensitizer (PS), was analyzed. The growth inhibition of Staphylococcus aureus exposed to artificial UV-A radiation and sunlight in the presence of Cap was investigated. After UV-A irradiation, 50 MUM Cap was able to decrease by three orders (with respect to the initial value) the number of S. aureus cells in early biofilms. However, this concentration was 500 times higher than that needed for eradicating planktonic cells. Importantly, under solar exposure, 100 MUM Cap was able to suppress sessile bacterial growth. Thus, this strategy is able to exert a bactericidal effect on sessile bacteria and to eradicate planktonic cells by exposing the Cap-containing sample to sunlight. PMID- 26133958 TI - Risk of Incident Coronary Heart Disease Events in Men Compared to Women by Menopause Type and Race. AB - BACKGROUND: We examined whether type of menopause affects sex differences in coronary heart disease (CHD) events and whether the impact is similar in blacks and whites. METHODS AND RESULTS: Participants were enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007 without CHD at baseline (n=23 086). Cox regression models were used to calculate the hazard of incident nonfatal CHD (definite or probable myocardial infarction) and acute CHD death, adjusting for age, age at last menstrual period <45 years, region, education level, income, diabetes, smoking, systolic blood pressure, lipid levels, albumin-creatinine ratio, physical activity, C-reactive protein, body mass index, waist circumference, and medication use. White women in natural menopause (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31, 0.66) and surgical menopause (HR, 0.65; 95% CI, 0.42, 0.99) had a reduced hazard of nonfatal events, compared to white men. Black women in natural menopause (HR, 0.69; 95% CI, 0.47, 1.03), but not surgical menopause (HR, 0.81; 95% CI, 0.51, 1.29), had a marginally reduced hazard of nonfatal events, compared to black men. Women had lower risk of acute CHD death than men regardless of their menopause type and race. CONCLUSIONS: Sex differences in the risk of incident CHD events were larger among whites than blacks and varied by type of menopause. Women consistently had a lower risk of incident CHD death than men, but the magnitude of sex differences was greater in whites than blacks for nonfatal events, regardless of menopause type. PMID- 26133960 TI - Assessment of the anatomical variation to be found in the normal tricuspid valve. AB - The normal tricuspid valve is tri-leaflet, supported by tendinous cords, which are themselves supported by papillary muscles. There can be marked variation in the anatomy of the normal tricuspid valve, which must be understood to differentiate it from pathological malformations. The tricuspid valve of 100 normal heart specimens was examined. The three leaflets of the tricuspid valve, along with the papillary muscles supporting the zones of apposition were identified, and details of the anatomy recorded and analyzed. All three leaflets were identified in all 100 hearts. The septal leaflet had tendinous cord attachments in 93 specimens to the ventricular septum. The medial papillary muscle had a single head in the majority of specimens, supporting the zone of apposition with the antero-superior leaflet in 97 specimens. The anterior papillary muscle attached to the mid-portion of the antero-superior leaflet in 62 specimens, and supplied the zone of apposition between the antero-superior and inferior leaflets in 81 specimens. There were rough zone cord attachments to the antero-superior leaflets in all specimens. The inferior leaflet had basal cord attachments in 87 specimens, with attachments to multiple small muscular heads in 37 specimens. The inferior papillary muscle was well formed in only 58 specimens. Although certain features are relatively constant, multiple variations in the normal tricuspid valve have been identified. Knowledge of these normal variations is necessary in understanding the function of this complex valve apparatus, along with the potential for pathology. PMID- 26133961 TI - Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion. AB - The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1alpha, tumor necrosis factor alpha (TNF-alpha), and macrophage inflammatory protein (MIP)-1beta and storage associated suppression of the production of DC IL-10, TNF-alpha, and IL-8. For the overall inflammatory response, IL-6, TNF-alpha, MIP-1alpha, MIP-1beta, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1beta significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications. PMID- 26133937 TI - The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill. AB - Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca(2+) dysregulation is present through altered Ca(2+) homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models. PMID- 26133962 TI - In vivo measurement of GABA transmission in healthy subjects and schizophrenia patients. AB - OBJECTIVE: Postmortem studies in schizophrenia reveal alterations in gene products that regulate the release and extracellular persistence of GABA. However, results of in vivo studies of schizophrenia measuring total tissue GABA with magnetic resonance spectroscopy (MRS) have been inconsistent. Neither the postmortem nor the MRS studies directly address the physiological properties of GABA neurotransmission. The present study addresses this question through an innovative positron emission tomography (PET) paradigm. METHOD: The binding of [(11)C]flumazenil, a benzodiazepine-specific PET radiotracer, was measured before and after administration of tiagabine (0.2 mg/kg of body weight), a GABA membrane transporter (GAT1) blocker, in 17 off-medication patients with schizophrenia and 22 healthy comparison subjects. Increased extracellular GABA, through GAT1 blockade, enhances the affinity of GABAA receptors for benzodiazepine ligands, detected as an increase in [(11)C]flumazenil tissue distribution volume (VT). RESULTS: [(11)C]Flumazenil VT was significantly increased across all cortical brain regions in the healthy comparison group but not in the schizophrenia group. This lack of effect was most prominent in the antipsychotic-naive schizophrenia group. In this subgroup, [(11)C]flumazenil DeltaVT in the medial temporal lobe was correlated with positive symptoms, and baseline [(11)C]flumazenil VT in the medial temporal lobe was negatively correlated with visual learning. In the healthy comparison group but not the schizophrenia group, [(11)C]flumazenil DeltaVT was positively associated with gamma-band oscillation power. CONCLUSIONS: This study demonstrates, for the first time, an in vivo impairment in GABA transmission in schizophrenia, most prominent in antipsychotic-naive individuals. The impairment in GABA transmission appears to be linked to clinical symptoms, disturbances in cortical oscillations, and cognition. PMID- 26133964 TI - Non-invasive gene targeting to the fetal brain after intravenous administration and transplacental transfer of plasmid DNA using PEGylated immunoliposomes. AB - Research was undertaken to establish transplacental delivery of active genes to fetal brain by a non-viral vector, antibody-specific targeted therapeutic procedure. PEGylated immunoliposomes (PILs) containing firefly luciferase DNA under the influence of the SV40 promoter injected intravenously into near-term pregnant mice produced luminometric evidence of CNS tissue luciferase activity at 48-h post-injection in all newborn pups. In utero delivery of this pGL3 DNA was shown after a single i.v. injection in maternal and neonatal brains, spleen and lesser amounts in lungs, with only negligible background levels in negative controls exposed to unencapsulated pDNA. In addition to studies of normal wild type mice, we similarly injected pregnant Lafora Knockout (EPM2a null-mutant) and demonstrated luciferase activity days later in the maternal and newborn pup brains of both types. Delivery of PILs containing a second reporter gene (the pSV40 beta-galactosidase transgene) transplacentally by the same procedure was also successful. Histochemical and biochemical demonstration of beta galactosidase was documented for all mutant and non-mutant neonates. Brain areas of highest Lafora body development (such as the hippocampus and pontine nuclei) showed intraneuronal beta-glucosidase activity. We conclude that receptor mediated transport of PIL-borne gene therapeutics across both the placental barrier as well as the fetal BBB in utero is feasible. PMID- 26133965 TI - Shape Transformation of Light-Responsive Pyrene-Containing Micelles and Their Influence on Cytoviability. AB - The amphiphilic pyrene-containing random copolymers with light-responsive pyrene ester bonds were synthesized by copolymerizing 1-pyrenemethyl acrylate (PA) and N,N-dimethylacrylamide (DMA). The P(DMA-co-PA) copolymers formed spherical micelles in water, which were transformed into nanorods as a result of cleavage of the pyrene ester bonds under UV irradiation. In vitro culture with A549 cells and Raw cells showed that compared to the nonphotodegradable ones, the photodegradable P(DMA-co-PA) micelles caused significantly higher cytotoxicity under the same UV irradiation. The intracellular reactive oxygen species (ROS) level had a positive correlation with the cytotoxicity regardless of the cell types. The nonphotodegradable pyrene-containing micelles produced a lower level of ROS under UV irradiation. However, the photodecomposable P(DMA-co-PA) micelles produced a significant higher level of ROS under the same trigger of UV irradiation, which caused the shape transformation of micelles to nanorods and higher cytotoxicity simultaneously. PMID- 26133963 TI - Molecular mechanisms and timing of cortical immune activation in schizophrenia. AB - OBJECTIVE: Immune-related abnormalities are commonly reported in schizophrenia, including higher mRNA levels for the viral restriction factor interferon-induced transmembrane protein (IFITM) in the prefrontal cortex. The authors sought to clarify whether higher IFITM mRNA levels and other immune-related disturbances in the prefrontal cortex are the consequence of an ongoing molecular cascade contributing to immune activation or the reflection of a long-lasting maladaptive response to an in utero immune-related insult. METHOD: Quantitative polymerase chain reaction was employed to measure mRNA levels for immune-related cytokines and transcriptional regulators, including those reported to regulate IFITM expression, in the prefrontal cortex from 62 schizophrenia and 62 healthy subjects and from adult mice exposed prenatally to maternal immune activation or in adulthood to the immune stimulant poly(I:C). RESULTS: Schizophrenia subjects had markedly higher mRNA levels for interleukin 6 (IL-6) (+379%) and interferon beta (+29%), which induce IFITM expression; lower mRNA levels for Schnurri-2 ( 10%), a transcriptional inhibitor that lowers IFITM expression; and higher mRNA levels for nuclear factor-kappaB (+86%), a critical transcription factor that mediates cytokine regulation of immune-related gene expression. In adult mice that received daily poly(I:C) injections, but not in offspring with prenatal exposure to maternal immune activation, frontal cortex mRNA levels were also markedly elevated for IFITM (+304%), multiple cytokines including IL-6 (+493%), and nuclear factor-kappaB (+151%). CONCLUSIONS: These data suggest that higher prefrontal cortex IFITM mRNA levels in schizophrenia may be attributable to adult, but not prenatal, activation of multiple immune markers and encourage further investigation into the potential role of these and other immune markers as therapeutic targets in schizophrenia. PMID- 26133967 TI - Survival after resection of perihilar cholangiocarcinoma-development and external validation of a prognostic nomogram. AB - BACKGROUND: The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS: A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS: For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS: The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials. PMID- 26133966 TI - Planning and reporting of quality-of-life outcomes in cancer trials. AB - BACKGROUND: Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN: Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS: Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS: About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers. PMID- 26133969 TI - Therapeutic Effectiveness in the Treatment of Experimental Bacterial Keratitis with Ion-activated Mucoadhesive Hydrogel. AB - PURPOSE: To investigate the therapeutic effectiveness of ion-activated mucoadhesive hydrogel system in the treatment of experimental bacterial keratitis. MATERIALS AND METHODS: Mucoadhesive systems were prepared using gellan or sodium alginate alone and combined with sodium carboxymethylcellulose (NaCMC) to enhance the gel bioadhesion properties. The in vivo antimicrobial efficacy of selected mucoadhesive systems was studied in an experiment on bacterial keratitis in rabbit's eyes and compared with that of the marketed conventional eyedrops. RESULTS: Ocular tolerance was studied in the eye of albino rabbits and tested formulations were non-irritant with no sign of inflammation. Better improvement in experimental bacterial keratitis in rabbit eyes was observed in animals treated with mucoadhesive hydrogel formulation (GG5 and GS5) compared with marketed drug solution. CONCLUSION: The developed system is a viable alternative to conventional eyedrops of GTN due to its ability to enhance bioavailability through its longer precorneal residence time. PMID- 26133968 TI - The relationship between the parenteral dose of fish oil supplementation and the variation of liver function tests in hospitalized adult patients. AB - BACKGROUND: Hepatic dysfunction is a complication associated with parenteral nutrition (PN). Our primary objective was to study the relationship between doses of intravenous fish oil (FO) emulsion in PN and the variation in the main liver function tests (LFTs) in hospitalized PN-treated adults. As a secondary objective, we studied the safety of FO administration. METHODS: We conducted a retrospective study in adult patients receiving FO supplementation in PN. Demographic, nutritional and safety variables were collected. Variation of LFTs was defined as the difference between values just before the first administration of FO and values at the end of PN. A multiple linear regression was performed to study the association between PN-lipids (FO or vegetable) and the variation of each LFT; the following variables were used to adjust the effect of lipids: sepsis, length of stay in the intensive care unit and lipids dose. Student t-test was used to study safety variables. Data were analyzed using SPSS 19.0. RESULTS: Patients (53, median age 68 years (24-90); 62% men) with the principal diagnosis of digestive neoplasm (42%) received PN for a median of 19 (7-75) days. In the multivariate analysis, the amount of FO was related to a decrease in gamma glutamyl transferase (GGT) (B = -2.23;CI95 % = -4.41/-0.05), a decrease in alkaline phosphatase (AP) (B = -1.23;CI95 % = -2.07/-0.37), and a decrease in alanine aminotransferase (ALT) (B = -0.82; CI95 % = -1.19/-0.44). No differences were found in safety variables. CONCLUSIONS: GGT, AP and ALT improved with FO PN supplementation. Moreover, the improvement was greater when the doses of FO were higher. FO administration in PN is safe. PMID- 26133970 TI - Endothelium-Dependent Relaxation Effect of Apocynum venetum Leaf Extract via Src/PI3K/Akt Signalling Pathway. AB - Botanical herbs are consumed globally not only as an essential diet but also as medicines or as functional/recreational food supplements. The extract of the Apocynum venetum leaves (AVLE), also known as Luobuma, exerts its antihypertensive effect via dilating the blood vessels in an endothelium- and concentration-dependent manner with optimal effect seen at as low as 10 ug/mL. A commercial Luoboma "antihypertensive tea" is available commercially in the western province of China. The present study seeks to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of AVLE in rat aortas and human umbilical vein endothelial cells (HUVECs). Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of polyethyleneglycol catalase (PP2, 20 uM; inhibitor of Src kinase), wortmannin (30 nM) and LY294002 (20 uM; PI3 (phosphatidylinositol3)-Kinase inhibitor), N(G)-nitro-L-arginine (L-NAME, 100 uM; endothelial NO synthase inhibitor (eNOS)) and ODQ (1 uM; soluble guanylyl cyclase inhibitor). Total nitrite and nitrate (NOx) level and protein expression of p-Akt and p-eNOS were measured. AVLE-induced endothelium-dependent relaxation was reduced by PP2, wortmannin and LY294002 and abolished by L-NAME and ODQ. AVLE significantly increased total NOx level in rat aortas and in HUVECs compared to control. It also instigated phosphorylation of Akt and eNOS in cultured HUVECs in a concentration-dependent manner and this was markedly suppressed by PP2, wortmannin and LY294002. AVLE also inhibited superoxide generated from both NADPH oxidase and xanthine/xanthine oxidase system. Taken together, AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway and possesses superoxide scavenging activity. PMID- 26133971 TI - Caffeine Affects Time to Exhaustion and Substrate Oxidation during Cycling at Maximal Lactate Steady State. AB - This study analyzed the effects of caffeine intake on whole-body substrate metabolism and exercise tolerance during cycling by using a more individualized intensity for merging the subjects into homogeneous metabolic responses (the workload associated with the maximal lactate steady state-MLSS). MLSS was firstly determined in eight active males (25 +/- 4 years, 176 +/- 7 cm, 77 +/- 11 kg) using from two to four constant-load tests of 30 min. On two following occasions, participants performed a test until exhaustion at the MLSS workload 1 h after taking either 6 mg/kg of body mass of caffeine or placebo (dextrose), in a randomized, double-blinded manner. Respiratory exchange ratio was calculated from gas exchange measurements. There was an improvement of 22.7% in time to exhaustion at MLSS workload following caffeine ingestion (95% confidence limits of +/-10.3%, p = 0.002), which was accompanied by decrease in respiratory exchange ratio (p = 0.001). These results reinforce findings indicating that sparing of the endogenous carbohydrate stores could be one of the several physiological effects of caffeine during submaximal performance around 1 h. PMID- 26133972 TI - Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats. AB - The effect of ellagic acid on oxidative stress and hypertension induced by Nomega Nitro-L-arginine methyl ester hydrochloride (L-NAME) was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day) for five weeks. L-NAME induced high systolic blood pressure (SBP) and increased heart rate (HR), hindlimb vascular resistance (HVR) and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg) prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability. PMID- 26133973 TI - Food Reformulation, Responsive Regulation, and "Regulatory Scaffolding": Strengthening Performance of Salt Reduction Programs in Australia and the United Kingdom. AB - Strategies to reduce excess salt consumption play an important role in preventing cardiovascular disease, which is the largest contributor to global mortality from non-communicable diseases. In many countries, voluntary food reformulation programs seek to reduce salt levels across selected product categories, guided by aspirational targets to be achieved progressively over time. This paper evaluates the industry-led salt reduction programs that operate in the United Kingdom and Australia. Drawing on theoretical concepts from the field of regulatory studies, we propose a step-wise or "responsive" approach that introduces regulatory "scaffolds" to progressively increase levels of government oversight and control in response to industry inaction or under-performance. Our model makes full use of the food industry's willingness to reduce salt levels in products to meet reformulation targets, but recognizes that governments remain accountable for addressing major diet-related health risks. Creative regulatory strategies can assist governments to fulfill their public health obligations, including in circumstances where there are political barriers to direct, statutory regulation of the food industry. PMID- 26133974 TI - Photoconversion of beta-Lapachone to alpha-Lapachone via a Protonation-Assisted Singlet Excited State Pathway in Aqueous Solution: A Time-Resolved Spectroscopic Study. AB - The photophysical and photochemical reactions of beta-lapachone were studied using femtosecond transient absorption, nanosecond transient absorption, and nanosecond time-resolved resonance Raman spectroscopy techniques and density functional theory calculations. In acetonitrile, beta-lapachone underwent an efficient intersystem crossing to form the triplet state of beta-lapachone. However, in water-rich solutions, the singlet state of beta-lapachone was predominantly quenched by the photoinduced protonation of the carbonyl group at the beta position (O9). After protonation, a series of fast reaction steps occurred to eventually generate the triplet state alpha-lapachone intermediate. This triplet state of alpha-lapachone then underwent intersystem crossing to produce the ground singlet state of alpha-lapachone as the final product. 1,2 Naphthoquinone is examined in acetonitrile and water solutions in order to elucidate the important roles that water and the pyran ring play during the photoconversion from beta-lapachone to alpha-lapachone. beta-Lapachone can also be converted to alpha-lapachone in the ground state when a strong acid is added to an aqueous solution. Our investigation indicates that beta-lapachone can be converted to alpha-lapachone by photoconversion in aqueous solutions by a protonation-assisted singlet excited state reaction or by an acid-assisted ground state reaction. PMID- 26133975 TI - Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: robust response of alveolar type 1 epithelial cells. AB - BACKGROUND: Engineered nanoparticles (NP) are being developed for inhaled drug delivery. This route is non-invasive and the major target; alveolar epithelium provides a large surface area for drug administration and absorption, without first pass metabolism. Understanding the interaction between NPs and target cells is crucial for safe and effective NP-based drug delivery. We explored the differential effect of neutral, cationic and anionic polystyrene latex NPs on the target cells of the human alveolus, using primary human alveolar macrophages (MAC) and primary human alveolar type 2 (AT2) epithelial cells and a unique human alveolar epithelial type I-like cell (TT1). We hypothesized that the bioreactivity of the NPs would relate to their surface chemistry, charge and size as well as the functional role of their interacting cells in vivo. METHODS: Amine (ANP) and carboxyl- surface modified (CNP) and unmodified (UNP) polystyrene NPs, 50 and 100 nm in diameter, were studied. Cells were exposed to 1-100 MUg/ml (1.25 125 MUg/cm(2); 0 MUg/ml control) NP for 4 and 24 h at 37 degrees C with or without the antioxidant, N-acetyl cysteine (NAC). Cells were assessed for cell viability, reactive oxygen species (ROS), oxidised glutathione (GSSG/GSH ratio), mitochondrial integrity, cell morphology and particle uptake (using electron microscopy and laser scanning confocal microscopy). RESULTS: ANP-induced cell death occurred in all cell types, inducing increased oxidative stress, mitochondrial disruption and release of cytochrome C, indicating apoptotic cell death. UNP and CNP exhibited little cytotoxicity or mitochondrial damage, although they induced ROS in AT2 and MACs. Addition of NAC reduced epithelial cell ROS, but not MAC ROS, for up to 4 h. TT1 and MAC cells internalised all NP formats, whereas only a small fraction of AT2 cells internalized ANP (not UNP or CNP). TT1 cells were the most resistant to the effects of UNP and CNP. CONCLUSION: ANP induced marked oxidative damage and cell death via apoptosis in all cell types, while UNP and CNP exhibited low cytotoxicity via oxidative stress. MAC and TT1 cell models show strong particle-internalization compared to the AT2 cell model, reflecting their cell function in vivo. The 50 nm NPs induced a higher bioreactivity in epithelial cells, whereas the 100 nm NPs show a stronger effect on phagocytic cells. PMID- 26133976 TI - Phylo-typing of clinical Escherichia coli isolates originating from bovine mastitis and canine pyometra and urinary tract infection by means of quadruplex PCR. AB - BACKGROUND: Escherichia coli is one of the major causative agents of bovine mastitis worldwide, and is typically associated with acute, clinical mastitis. Besides this, E. coli strains which belong to the extra-intestinal pathogenic group are also the major cause of urinary tract infections and pyometra in dogs. OBJECTIVES: In this study, it was aimed to investigate phylo-groups/subgroups in 155 E. coli isolates obtained from acute bovine mastitis, 43 from urinary tract infections of dogs and 20 from canine pyometra by a formerly described triplex PCR and recently described new quadruplex polymerase chain reaction (PCR) method. RESULTS: Group A1 (n = 118; 76%) and B1 (n = 71; 46%) were found to be the most prevalent groups by triplex and quadruplex PCR assays in mastitis isolates, respectively. Phylo-typing of 43 urinary tract isolates also revealed that most of the isolates belonged to A1 (n = 23; 54%) by triplex and B2 (n = 36; 84%) by quadruplex PCR assays. The isolates assigned as group A1 (n = 17; 85%) by triplex PCR could not be classified by quadruplex PCR in pyometra isolates. CONCLUSIONS: The results support the hypothesis that E. coli strains isolated from bovine mastitis cases are environmental. Also, groups C, E and F were identified as new phylo-groups for the first time in acute bovine mastitis cases. The comparison of triplex PCR with quadruplex PCR results revealed that most of the groups assigned in triplex PCR were altered by quadruplex PCR assay. PMID- 26133977 TI - Staff perspectives of barriers to women accessing birthing services in Nepal: a qualitative study. AB - BACKGROUND: Nepal has made significant progress with regard to reducing the maternal mortality ratio but a major challenge remains the under-utilisation of skilled birth attendants who are predominantly facility based. Studies have explored women's views of the barriers to facility birth; however the voices of staff who offer services have not been studied in detail. This research explores the views of staff as to the key reasons why pregnant women do not give birth in a maternity-care facility. METHODS: This mixed methods study comprised qualitative interviews and non-participant observation. The study was conducted in two small non-governmental hospitals, one semi-rural and one urban, in Kathmandu Valley. Twenty interviews were conducted with health care providers and other staff in these hospitals. The interviews were undertaken with the aid of a Nepali translator, with some interviews being held in English. Twenty-five hours of non-participant observation was conducted in both maternity hospitals . Both observation and interview data were analysed thematically. Ethical approval was granted by the Nepal Research Health Council and Bournemouth University's Ethics Committee. RESULTS: Key themes that emerged from the analysis reflected barriers that women experience in accessing services at different conceptual levels and resembled the three phases of delay model by Thaddeus and Maine. This framework is used to present the barriers. First Phase Delays are: 1) lack of awareness that the facility/services exist; 2) women being too busy to attend; 3) poor services; 4) embarrassment; and 5) financial issues. Themes for the second Phase of Delay are: 1) birthing on the way; and 2) by-passing the facility in favour of one further away. The final Phase involved: 1) absence of an enabling environment; and 2) disrespectful care. CONCLUSION: This study highlights a multitude of barriers, not all of the same importance or occuring at the same time in the pregnancy journey. It is clear that staff are aware of many of the barriers for women in reaching the facility to give birth, and these fit with previous literature of women's views. However, staff had limited insight into barriers occuring within the facility itself and were more likely to suggest that this was a problem for other institutions and not theirs. PMID- 26133978 TI - Renal vein thrombosis mimicking urinary calculus: a dilemma of diagnosis. AB - BACKGROUND: Renal vein thrombosis (RVT) with flank pain, and hematuria, is often mistaken with renal colic originating from ureteric or renal calculus. Especially in young and otherwise healthy patients, clinicians are easily misled by clinical presentation and calcified RVT. CASE PRESENTATION: A 38-year-old woman presented with flank pain and hematuria suggestive of renal calculus on ultrasound. She underwent extracorporeal shock wave lithotripsy that failed, leading to the recommendation that percutaneous lithotomy was necessary to remove the renal calculus. In preoperative view of the unusual shape of the calculus without hydronephrosis, noncontrast computed tomography was taken and demonstrated left ureteric calculus. However computed tomography angiography revealed, to our surprise, a calcified RVT that was initially thought to be a urinary calculus. CONCLUSION: This case shows that a calcified RVT might mimic a urinary calculus on conventional ultrasonography and ureteric calculus on noncontrast computed tomography. Subsequent computed tomography angiography disclosed that a calcified RVT caused the imaging findings, thus creating a potentially dangerous clinical pitfall. Hence, it is suggested that the possibility of a RVT needs to be considered in the differential diagnosis whenever one detects an uncommon shape for a urinary calculus. PMID- 26133979 TI - Knockdown of zinc transporter ZIP5 (SLC39A5) expression significantly inhibits human esophageal cancer progression. AB - ZIP5 is a central player in mammalian zinc metabolism. Studies suggest that ZIP5 is differentially expressed during esophageal tumorigenesis, yet the role of ZIP5 in esophageal cancer cells has not yet been clarified. Immunohistochemistry, western blotting and qRT-PCR techniques were used to detect ZIP5 expression in esophageal squamous cell carcinoma (ESCC) tissues. We established a stable knockdown ZIP5 cell line (KYSE170K) derived from the ESCC cell line KYSE170. We conducted MTT and CCK-8 assays to determine the role of ZIP5 in cell proliferation, Transwell assays to detect migration and invasion, and flow cytometry (FCM) to detect apoptosis and cell cycle percentage using KYSE170K cells. We conducted a gene profiling study to detect the expression of genes related to tumor progression. The results demonstrated that ZIP5 protein and mRNA expression was highest in ESCC, intermediate in para-carcinoma and lowest in normal tissue. ZIP5 knockdown decreased proliferation by 28 and 38%, respectively, according to the MTT and CCK-8 assays. Migration and invasion decreased by 54 and 68%, respectively, according to the Transwell assays. COX2 expression was decreased by 68 and 75% at the mRNA and protein level, respectively, and cyclin D1 mRNA and protein expression was decreased following 62 and 60%, respectively, by knockdown of ZIP5, which upregulated the mRNA and protein expression of E-cadherin by 80 and 60%, respectively. ZIP5 knockdown inhibited the proliferation, migration and invasion of ESCC and suppressed COX2, cyclin D1 and E-cadherin expression, which led to the inhibition of cell progression in ESCC. PMID- 26133980 TI - Probe-based confocal laser endomicroscopy quantitative morphometric markers associated with portal hypertension in duodenal mucosa. AB - BACKGROUND & AIMS: Early detection of portal hypertension (PH) may help to prevent the morbidity of late-stage cirrhosis by stratifying disease severity and enabling disease-modifying interventions in potentially reversible conditions like non-alcoholic fatty liver disease and alcoholic hepatitis. This study seeks to correlate morphometric features by confocal endomicroscopy with established surrogate clinical markers of PH. METHODS: Patients with and without PH scheduled for upper endoscopy at VA Boston participated in this IRB-approved study. Real time probe-based confocal endomicroscopy (pCLE) was performed in the duodenum. Vascular and epithelial morphometry was performed off-line, in a blinded manner, using image-processing software. RESULTS: Morphometric analysis of pCLE images from 16 patients with PH and 15 control patients was performed. Statistically significant differences were observed among control and PH patients for average vessel diameter (AVD: 11.7 MUm vs. 17.1 MUm), average vessel branching (AVB: 0.11 vs. 0.31 bifurcations per image frame), and average columnar cell height (ACCH: 40.0 MUm vs. 52.0 MUm). Spearman correlations comparing AVD, AVB and ACCH to portal gastropathy scores (0.86, 0.44 and 0.70) and to grade of oesophageal varices (0.88, 0.41 and 0.66) were statistically significant. Similarly, Pearson correlations of AVD and ACCH to spleen size (0.72 and 0.57), platelet count ( 0.69 and -0.40) and the platelet count/spleen size ratio (-0.69 and -0.41) were also found to be statistically significant. CONCLUSIONS: Duodenal pCLE reveals microvascular dilatation and altered epithelial cell volume/morphology in PH. These morphometric pCLE markers correlate with surrogate markers of PH. Additional studies will define the correlation between microscopic vascular patterns, epithelial cell volume and the hepatic venous pressure gradient. PMID- 26133981 TI - Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study. AB - The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different granulomas share core similarities in their immunological/inflammatory characteristics, they also exhibit significant divergence. Despite similar numbers of CD68+ macrophages in the different lesions, the extent of immune reactivity, as determined by the density of CD3+ T cells in the macrophage rich areas, and the extent of fibrosis, shows considerable variation. Both quantitative and qualitative differences among significantly differentially expressed genes (SDEG) were noted in each of the lesion types studied. Further, network/pathway analysis of SDEG revealed differential regulation of inflammatory response, immune cell trafficking, and cell mediated immune response in the different lesions. Our data highlight the formidable challenges facing ongoing efforts to identify peripheral blood biomarkers due to the diversity of lesion types and complexity of local immune responses in the lung. PMID- 26133982 TI - Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection. AB - Glycans play important roles in host-microbe interactions. Tissue-specific expression patterns of the blood group glycosyltransferase beta-1,4-N acetylgalactosaminyltransferase 2 (B4galnt2) are variable in wild mouse populations, and loss of B4galnt2 expression is associated with altered intestinal microbiota. We hypothesized that variation in B4galnt2 expression alters susceptibility to intestinal pathogens. To test this, we challenged mice genetically engineered to express different B4galnt2 tissue-specific patterns with a Salmonella Typhimurium infection model. We found B4galnt2 intestinal expression was strongly associated with bacterial community composition and increased Salmonella susceptibility as evidenced by increased intestinal inflammatory cytokines and infiltrating immune cells. Fecal transfer experiments demonstrated a crucial role of the B4galnt2-dependent microbiota in conferring susceptibility to intestinal inflammation, while epithelial B4galnt2 expression facilitated epithelial invasion of S. Typhimurium. These data support a critical role for B4galnt2 in gastrointestinal infections. We speculate that B4galnt2 specific differences in host susceptibility to intestinal pathogens underlie the strong signatures of balancing selection observed at the B4galnt2 locus in wild mouse populations. PMID- 26133983 TI - The Porcine TSPY Gene Is Tricopy but Not a Copy Number Variant. AB - The testis-specific protein Y-encoded (TSPY) gene is situated on the mammalian Y chromosome and exhibits some remarkable biological characteristics. It has the highest known copy number (CN) of all protein coding genes in the human and bovine genomes (up to 74 and 200, respectively) and also shows high individual variability. Although the biological function of TSPY has not yet been elucidated, its specific expression in the testis and several identified binding domains within the protein suggests roles in male reproduction. Here we describe the porcine TSPY, as a multicopy gene with three copies located on the short arm of the Y-chromosome with no variation at three exon loci among 20 animals of normal reproductive health from four breeds of domestic pigs (Pietrain, Landrace, Duroc and Yorkshire). To further investigate the speculation that porcine TSPY is not a copy number variant, we have included five Low-fertility boars and five boars with exceptional High-fertility records. Interestingly, there was no difference between the High- and Low-fertile groups, but we detected slightly lower TSPY CN at all three exons (2.56-2.85) in both groups, as compared to normal animals, which could be attributed to technical variability or somatic mosaicism. The results are based on both relative quantitative real-time PCR (qPCR) and droplet digital PCR (ddPCR). Chromosomal localization of the porcine TSPY was done using fluorescence in situ hybridization (FISH) with gene specific PCR probes. PMID- 26133984 TI - The Frequency of Unhealthy Food Advertising on Mainland Chinese Television (TV) and Children and Adolescents' Risk of Exposure to Them. AB - OBJECTIVE: To conduct an analysis of the frequency of unhealthy food advertising on mainland Chinese television (TV) and children and adolescents' risk of exposure to them. METHODS: The frequencies of all types of advertisements (ads) on forty TV channels in mainland China, the exact ad broadcast times, and the name and brand of all snacks and western fast foods advertised were recorded from 0800 hours to 2400 hours on both a weekday and a weekend day in a week. The difference in the frequencies of the diverse types of ads over eight time intervals (each time interval was 2 hours) were compared, and the trends in ad frequencies during the time intervals were described. RESULTS: The TV channels broadcast 155 (91-183) (expressed as median [P25-P75]) food ads, 87 (38-123) snack ads, 49 (11-85) beverage ads, and 58 (25-76) ads of snacks suitable for limited consumption (SSLCs) in a day. The proportion of snack ads among food ads (SPF%) was 55.5% (40.3%-71.0%), and the proportion of SSLC ads among snack ads (LPS%) was 67.4% (55.4%-79.3%). The ad frequencies for food, snacks, SSLCs, and beverages demonstrated significant differences among the eight time intervals (all P=0.000). TV channels broadcast the most frequent ads for food, snacks, SSLCs, and beverages during the time interval from 2000 hours to 2200 hours among the eight time intervals. CONCLUSIONS: Chinese children and adolescents may be at a high risk of exposure to unhealthy food advertising on TV. Reducing the exposure risk strongly requires multisectoral cooperation. PMID- 26133985 TI - Source Tracking and Succession of Kimchi Lactic Acid Bacteria during Fermentation. AB - This study aimed at evaluating raw materials as potential lactic acid bacteria (LAB) sources for kimchi fermentation and investigating LAB successions during fermentation. The bacterial abundances and communities of five different sets of raw materials were investigated using plate-counting and pyrosequencing. LAB were found to be highly abundant in all garlic samples, suggesting that garlic may be a major LAB source for kimchi fermentation. LAB were observed in three and two out of five ginger and leek samples, respectively, indicating that they can also be potential important LAB sources. LAB were identified in only one cabbage sample with low abundance, suggesting that cabbage may not be an important LAB source. Bacterial successions during fermentation in the five kimchi samples were investigated by community analysis using pyrosequencing. LAB communities in initial kimchi were similar to the combined LAB communities of individual raw materials, suggesting that kimchi LAB were derived from their raw materials. LAB community analyses showed that species in the genera Leuconostoc, Lactobacillus, and Weissella were key players in kimchi fermentation, but their successions during fermentation varied with the species, indicating that members of the key genera may have different acid tolerance or growth competitiveness depending on their respective species. PMID- 26133986 TI - Performance analysis of a dedicated breast MR-HIFU system for tumor ablation in breast cancer patients. AB - MR-guided HIFU ablation is a promising technique for the non-invasive treatment of breast cancer. A phase I study was performed to assess the safety and treatment accuracy and precision of MR-HIFU ablation in breast cancer patients (n=10) using a newly developed MR-HIFU platform dedicated to applications in the breast. In this paper a technical analysis of the performance of the dedicated breast MR-HIFU system during breast tumors ablation is described. The main points of investigation were the spatial targeting accuracy and precision of the system and the performance of real-time respiration-corrected MR thermometry.The mean targeting accuracy was in the range of 2.4-2.6 mm, whereas the mean targeting precision was in the range of 1.5-1.8 mm. To correct for respiration-induced magnetic field fluctuations during MR temperature mapping a look-up-table (LUT) based correction method was used. An optimized procedural sedation protocol in combination with the LUT-based correction method allowed for precise MR thermometry during the ablation procedure (temperature standard deviation <3 degrees C). No unwanted heating in the near field (i.e. skin) nor in the far field (pectoral muscle) was detected.The newly developed dedicated breast MR-HIFU system allows for safe, accurate and precise ablation of breast tumors. PMID- 26133987 TI - Site promiscuity of coliphage HK022 integrase as tool for gene therapy. PMID- 26133988 TI - Molecular cloning and characterization of presenilin gene in Bombyx mori. AB - Presenilin (PS), the catalytic core of the gamma-secretase complex, is considered to be a causative protein of the early-onset familial form of Alzheimer's disease. Aging is a risk factor for Alzheimer's disease and a number of genetic studies have utilized Bombyx mori (B. mori) as a model, making it possible to use B. mori to investigate Alzheimer's disease. However, the homologous gene of human PS in B. mori has remained to be elucidated. In the present study, the PS homologue gene in B. mori was identified and characterized, and six B. mori presenilin (BmPS) mRNA transcripts were generated by selecting multiple transcription start sites and/or alternative splice sites. The longest mRNA of BmPS (termed BmPS1) contains a 153 nt 5' untranslated region (UTR), a 1,440 nt open reading frame and a 1,063 nt 3' UTR. The predicted protein of BmPS1 consists of 479 amino acid residues and has two highly-conserved aspartate residues, which form the catalytic core of aspartic proteases. It exhibits a sequence identity of ~44 and 51% with homologues in Homo sapiens and Drosophila melanogaster, respectively. However, the amino acid sequence of the BmPS loop region does not completely match between the two B. mori strains R13Q and Dazao. Genomic analysis revealed that B. mori had a single copy of the BmPS gene, which was composed of 14 exons. A total of four isoforms of BmPS (BmPS-A, -B, -C and -D) owing to multiple transcriptional start sites and alternative splice sites were identified. The alternative splicing events occurring in the loop region improved the diversity of the BmPS protein and were detectable in all tissues, as determined using reverse transcription quantitative polymerase chain reaction (RT qPCR). Furthermore, the expression levels of BmPS in the brain at different developmental stages were detected using RT-qPCR, and significantly higher expression levels of BmPS were found in the adult stage compared with those in the larval and pupal stages. The present study on BmPS provided insight into the pathogenesis of Alzheimer's disease and mechanisms of silkworm developmental regulation. PMID- 26133990 TI - Four-Year-Olds Use a Mixture of Spatial Reference Frames. AB - Keeping track of unseen objects is an important spatial skill. In order to do this, people must situate the object in terms of different frames of reference, including body position (egocentric frame of reference), landmarks in the surrounding environment (extrinsic frame reference), or other attached features (intrinsic frame of reference). Nardini et al. hid a toy in one of 12 cups in front of children, turned the array when they were not looking, and then asked them to point to the cup with the toy. This forced children to use the intrinsic frame (information about the array of cups) to locate the hidden toy. Three-year olds made systematic errors by using the wrong frame of reference, 4-year-olds were at chance, and only 5- and 6-year-olds were successful. Can we better understand the developmental change that takes place at four years? This paper uses a modelling approach to re-examine the data and distinguish three possible strategies that could lead to the previous results at four years: (1) Children were choosing cups randomly, (2) Children were pointing between the egocentric/extrinsic-cued location and the correct target, and (3) Children were pointing near the egocentric/extrinsic-cued location on some trials and near the target on the rest. Results heavily favor the last possibility: 4-year-olds were not just guessing or trying to combine the available frames of reference. They were using the intrinsic frame on some trials, but not doing so consistently. These insights suggest that accounts of improving spatial performance at 4 years need to explain why there is a mixture of responses. Further application of the selected model also suggests that children become both more reliant on the correct frame and more accurate with any chosen frame as they mature. PMID- 26133989 TI - The Role of Vascular Endothelial Growth Factor Receptor-1 Signaling in the Recovery from Ischemia. AB - Vascular endothelial growth factor (VEGF) is one of the most potent angiogenesis stimulators. VEGF binds to VEGF receptor 1 (VEGFR1), inducing angiogenesis through the receptor's tyrosine kinase domain (TK), but the mechanism is not well understood. We investigated the role of VEGFR1 tyrosine kinase signaling in angiogenesis using the ischemic hind limb model. Relative to control mice, blood flow recovery was significantly impaired in mice treated with VEGFA-neutralizing antibody. VEGFR1 tyrosine kinase knockout mice (TK-/-) had delayed blood flow recovery from ischemia and impaired angiogenesis, and this phenotype was unaffected by treatment with a VEGFR2 inhibitor. Compared to wild type mice (WT), TK-/- mice had no change in the plasma level of VEGF, but the plasma levels of stromal-derived cell factor 1 (SDF-1) and stem cell factor, as well as the bone marrow (BM) level of pro-matrix metalloproteinase-9 (pro-MMP-9), were significantly reduced. The recruitment of cells expressing VEGFR1 and C-X-C chemokine receptor type 4 (CXCR4) into peripheral blood and ischemic muscles was also suppressed. Furthermore, WT transplanted with TK-/- BM significantly impaired blood flow recovery more than WT transplanted with WT BM. These results suggest that VEGFR1-TK signaling facilitates angiogenesis by recruiting CXCR4+VEGFR1+ cells from BM. PMID- 26133991 TI - Towards an Understanding of the Interactions between Freshwater Inflows and Phytoplankton Communities in a Subtropical Estuary in the Gulf of Mexico. AB - Subtropical estuaries worldwide face increased pressure on their ecosystem health and services due to increasing human population growth and associated land use/land cover changes, expansion of ports, and climate change. We investigated freshwater inflows (river discharge) and the physico-chemical characteristics of Galveston Bay (Texas, USA) as mechanisms driving variability in phytoplankton biomass and community composition between February 2008 and December 2009. Results of multivariate analyses (hierarchical cluster analysis, PERMANOVA, Mantel test, and nMDS ordination coupled to environmental vector fitting) revealed that temporal and spatial differences in phytoplankton community structure correlate to differences in hydrographic and water quality parameters. Spatially, phytoplankton biomass and community composition responded to nutrient loading from the San Jacinto River in the northwest region of the bay (consistent with nutrient limitation) while hydraulic displacement (and perhaps other processes) resulted in overall lower biomass in the Trinity River delta (northeast region). The influence of inflows on phytoplankton diminished along a north to south gradient in the bay. Temporally, temperature and variables associated with freshwater inflow (discharge volume, salinity, inorganic nitrogen and phosphorus concentrations) were major influences on phytoplankton dynamics. Dissolved inorganic nitrogen: phosphorus (DIN:DIP) ratios suggest that phytoplankton communities will be predominately nitrogen limited. Diatoms dominated during periods of moderate to high freshwater inflows in winter/spring and were more abundant in the upper bay while cyanobacteria dominated during summer/fall when inflow was low. Given the differential influences of freshwater inflow on the phytoplankton communities of Galveston Bay, alterations upstream (magnitude, timing, frequency) will likely have a profound effect on downstream ecological processes and corresponding ecosystem services. PMID- 26133992 TI - Intraoperative Endovascular Stent-graft Repair of a Popliteal Artery Laceration and Occlusion during Total Knee Arthroplasty. AB - Injury to the popliteal vessels during total knee arthroplasty is a rare but serious complication that can cause permanent loss of function. Its incidence has been reported to be on the rise with an incidence ranging from 0.03% to 0.51%. Although rare, these complications deserve attention as they may have dire consequences, with mortality reaching 7%, amputation in up to 42%, and other morbidities such as ischemic nerve injury (foot drop). We present a case of a 78 year-old female with a pulseless limb after intraoperative injury of the popliteal artery during total knee replacement surgery who was immediately investigated with digital subtraction angiography and found to have a popliteal artery laceration with significant bleeding and a distal occlusion of the artery that was repaired endovascularly. A covered stent graft was used to simultaneously exclude the arterial laceration and to recanalize the localized popliteal occlusion. To our knowledge, this is the first report of an iatrogenic popliteal artery laceration and occlusion treated endovascularly in the intraoperative time. PMID- 26133993 TI - Very Long Segment Congenital Thoracoabdominal Aortic Coarctation (Diffuse Aortic Dysplasia) with Infrarenal Aortobi-Iliac and Cavobi-Iliac Aplasia in a 30-Year Old Patient. AB - Congenital dysplastic aortic syndromes range from coarctation at the aortic isthmus to more extended aortic disease (midaortic syndrome). The latter is usually restricted to dysplastic aortic segments of up to 15 cm. Long segment dysplasia of the entire abdominal or thoracic aorta is extremely rare. This case of a 30-year-old patient with a very long segment congenital thoracoabdominal aortic coarctation and infrarenal aortobi-iliac and cavobi-iliac aplasia represents to our knowledge the most extended congenital vascular malformation in a surviving adult patient. The developed extensive collateral pathways ensured the survival of the patient, so that the main clinical manifestation was a refractory hypertension. Because of the extent of the disease, open surgery represented the only viable option. Interestingly, after 30 years of uncontrollable hypertension, the patient's blood pressure promptly responded to surgical treatment. A concomitant infrarenal aplasia of both the aorta and cava vein is also very unusual and points to a major developmental deficit during vascular embryogenesis. PMID- 26133994 TI - A Comparison of Training Experience, Training Satisfaction, and Job Search Experiences between Integrated Vascular Surgery Residency and Traditional Vascular Surgery Fellowship Graduates. AB - BACKGROUND: The first 2 integrated vascular residents in the United States graduated in 2012, and in 2013, 11 more entered the job market. The purpose of this study was to compare the job search experiences of the first cohort of integrated 0 + 5 graduates to their counterparts completing traditional 5 + 2 fellowship programs. METHODS: An anonymous, Web-based, 15-question survey was sent to all 11 graduating integrated residents in 2013 and to the 25 corresponding 5 + 2 graduating fellows within the same institution. Questions focused on the following domains: training experience, job search timelines and outcomes, and overall satisfaction with each training paradigm. RESULTS: Survey response was nearly 81% for the 0 + 5 graduates and 64% for the 5 + 2 graduates. Overall, there was no significant difference between residents and fellows in the operative experience obtained as measured by the number of open and endovascular cases logged. Dedicated research time during the entire training period was similar between residents and fellows. Nearly all graduates were extremely satisfied with their training and had positive experiences during their job searches with respect to starting salaries, numbers of offers, and desired practice type. More 0 + 5 residents chose academic and mixed practices over private practices compared with 5 + 2 fellowship graduates. CONCLUSIONS: Although longer term data are needed to understand the impact of the addition of 0 + 5 graduating residents to the vascular surgery work force, preliminary survey results suggest that both training paradigms (0 + 5 and 5 + 2) provide positive training experiences that result in excellent job search experiences. Based on the current and future need for vascular surgeons in the work force, the continued growth and expansion of integrated 0 + 5 vascular surgery residency positions as an alternative to traditional fellowship training is thus far justified. PMID- 26133995 TI - Open Thrombectomy for Primary Acute Mesentericoportal Venous Thrombosis--Should It Be Done? AB - Mesentericoportal venous thrombosis (MVT) is a rare condition, accounting for 5 15% of acute mesenteric ischemia. Primary MVT is even rarer, with some reports quoting an incidence rate of 10-30% of reported cases. It presents a diagnostic challenge and is associated with a significant mortality rate, ranging from 13% to 50%. As it is an uncommon condition, the evidence in current literature regarding the treatment of MVT is limited. We discuss our surgical experience with a case of acute primary MVT that was managed with good clinical outcome and discuss the current evidence for the treatment of acute MVT. A 50-year-old Chinese lady with no significant past medical history presented with a 2-day history of abdominal pain and epigastric tenderness on examination. Computed tomography of her abdomen and pelvis showed evidence of extensive acute thrombi present in portal confluence extending into the superior mesenteric vein, associated with submucosal edema in some central jejunal loops. Despite systemic anticoagulation therapy with intravenous heparin, the patient deteriorated clinically, and decision was made for an exploratory laparotomy, small bowel resection, and open thrombectomy. Postoperative recovery was uneventful. She was discharged on postoperative day 13 with lifelong oral anticoagulation. In conclusion, we describe the successful management of a patient with extensive acute primary MVT where open thrombectomy was performed together with small bowel resection. PMID- 26133996 TI - Stress Management in Patients Undergoing Carotid Endarterectomy for Carotid Artery Stenosis: A Pilot Randomized Controlled Trial. AB - BACKGROUND: Psychological stress is common to patients submitted to cardiovascular operations. The purpose of this pilot, single-center, open-label, randomized controlled trial was to investigate the effects of a stress management program (SMP) on patients undergoing carotid endarterectomy (CEA). METHODS: A sample of 24 patients with significant (>70%) carotid stenosis was finally randomized to SMP (intervention group; n = 12) or no-stress management intervention (control group; n = 12) before CEA. SMP consisted of 2 relaxation techniques (relaxation-breathing and guided imagery) before and 8 weeks after CEA. Measurements included Perceived Stress Scale (PSS), Hospital Anxiety and Depression Scale (HADS), Health Locus of Control Scale (HLC), and blood pressure and heart rate. RESULTS: The 2 groups did not differ in terms of demographic characteristics, vascular risk factors, and baseline psychometric measurements. No delay on the time of surgery was caused by the practice of the relaxation techniques. Both perceived stress and anxiety improved within the intervention group at the end of the program (P = 0.005 and P = 0.007, respectively). No improvement in PSS-14, HLC, and HADS scores were documented in control group at the end of the 8-week follow-up period. The intervention group had lower PSS-14 scores at 8 weeks after CEA (median PSS-14 score, 20 points; range, 10-28) compared with control group (median PSS, 25 points; range, 11-47; P = 0.026). No significant effect of SMP was found for blood pressure and heart rate measurements. CONCLUSIONS: Our results indicate that relaxation techniques appear to be beneficial in terms of stress and anxiety reduction in patients undergoing CEA. These findings require independent confirmation in the setting of a larger, double-blind randomized controlled trial. PMID- 26133997 TI - A Case of Mesenchymal Chondrosarcoma Arising from the Femoral Vein with 8 Years of Follow-up. AB - Mesenchymal chondrosarcoma (MCS) is an infrequent malignancy of bone and soft tissue that is characterized by a peculiar bimorphic histologic pattern with areas of undifferentiated malignant small cells surrounding well-differentiated cartilaginous islands. Involvement of the large vessels is a rare occurrence. Here, we report a case of MCS arising from the femoral vein that was treated by wide-margin resection combined with autogenous vein revascularization and then followed up for 8 years. The long-term postoperative results showed distant metastasis to the pancreas and both lobes of the lung, without recurrence at the primary site. This case indicates that for MCS arising from the femoral vein, although wide-margin resection combined with autogenous vein revascularization may avoid recurrence at the primary site, this treatment strategy has no obvious benefit for controlling long-term distant metastases. PMID- 26133998 TI - Effect of fiber diameter on the assembly of functional 3D cardiac patches. AB - The cardiac ECM has a unique 3D structure responsible for tissue morphogenesis and strong contractions. It is divided into three fiber groups with specific roles and distinct dimensions; nanoscale endomysial fibers, perimysial fibers with a diameter of 1 MUm, and epimysial fibers, which have a diameter of several micrometers. We report here on our work, where distinct 3D fibrous scaffolds, each of them recapitulating the dimension scales of a single fiber population in the heart matrix, were fabricated. We have assessed the mechanical properties of these scaffolds and the contribution of each fiber population to cardiomyocyte morphogenesis, tissue assembly and function. Our results show that the nanoscale fiber scaffolds were more elastic than the microscale scaffolds, however, cardiomyocytes cultured on microscale fiber scaffolds exhibited enhanced spreading and elongation, both on the single cell and on the engineered tissue levels. In addition, lower fibroblast proliferation rates were observed on these microscale topographies. Based on the collected data we have fabricated composite scaffolds containing micro and nanoscale fibers, promoting superior tissue morphogenesis without compromising tissue contraction. Cardiac tissues, engineered within these composite scaffolds exhibited superior function, including lower excitation threshold and stronger contraction forces than tissue engineered within the single-population fiber scaffolds. PMID- 26133999 TI - Circuital characterisation of space-charge motion with a time-varying applied bias. AB - Understanding the behaviour of space-charge between two electrodes is important for a number of applications. The Shockley-Ramo theorem and equivalent circuit models are useful for this; however, fundamental questions of the microscopic nature of the space-charge remain, including the meaning of capacitance and its evolution into a bulk property. Here we show that the microscopic details of the space-charge in terms of resistance and capacitance evolve in a parallel topology to give the macroscopic behaviour via a charge-based circuit or electric-field based circuit. We describe two approaches to this problem, both of which are based on energy conservation: the energy-to-current transformation rule, and an energy-equivalence-based definition of capacitance. We identify a significant capacitive current due to the rate of change of the capacitance. Further analysis shows that Shockley-Ramo theorem does not apply with a time-varying applied bias, and an additional electric-field-based current is identified to describe the resulting motion of the space-charge. Our results and approach provide a facile platform for a comprehensive understanding of the behaviour of space-charge between electrodes. PMID- 26134000 TI - 2beta, 3beta, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) isolated from Actinidia chinensis Radix inhibits NCI-H460 cell proliferation by decreasing NF-kappaB expression. AB - A natural ursolic compound, 2beta, 3beta, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) was isolated from the root of Actinidia chinensis Planch (A. chinensis Radix). Since a large number of triterpenoid compound has marked anticancer effects toward various types of cancer cell lines in vitro, this study was carried out to investigate the anticancer effect of TUA in non-small cell lung cancer cells (NSCLCCs) and the underlying apoptotic mechanism of TUA was examined in NCI-H460 cell lines. Cell proliferation, apoptosis and cell cycle were measured using a cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The activity of transcription factor NF-kappaB was determined by EMSA method. The expression of apoptosis- and proliferation-related proteins was determined by western blotting. The effect of TUA on NF-kappaB mRNA expression in NCI-H460 cells was detected by RT-PCR. TUA significantly suppressed the viability of NCI-H460 cells. Also, TUA significantly increased the sub G1 population by cell cycle analysis and in a concentration dependent manner in NCI-H460 cells. Such an effect was accompanied by p65 (NF-kappaB subunit) inactivation by an inhibition of IkappaBalpha phosphorylation, and by inhibition of p65 mRNA expressions. Consistently Overall, our findings suggest that TUA induces apoptosis via inhibition of NF-kappaB (p65) expression level and activation of IkappaBalpha in NCI-H460 cells as a potent anticancer candidate for lung cancer treatment. PMID- 26134001 TI - Improvement of in vivo anticancer and antiangiogenic potential of thalidomide derivatives. AB - The strategy of antiangiogenic drugs is based on inhibiting formation of new blood vessels as alternative to limit cancer progression. In this work, we investigated the antitumor and antiangiogenic potential of eight thalidomide derivatives. Most of the molecules was not cytotoxic but 2a, 2d and 3d revealed weak antiproliferative activity on HL-60, Sarcoma 180 (S180) and normal peripheral blood mononuclear cells. Thalidomide, 2a and 2b were able to inhibit tumor growth (53.5%, 67.9% and 67.4%, respectively) in S180-bearing mice and presented moderate and reversible toxicity on liver, kidneys and spleens. Both analogs (2a and 2b) inhibited cell migration of endothelial (HUVEC) and melanoma cells (MDA/MB-435) at 50MUg/mL. Immunohistochemistry labeling assays with CD-31 (PECAM-1) antibody showed microvascular density (MVD) was significantly reduced in thalidomide, 2a and 2b groups (30+/-4.9, 64.6+/-1.8 and 46.5+/-19.5%, respectively) (p<0.05). Neovascularization evaluated by Chorioallantoic Membrane Assay (CAM) with compounds 2a and 2b showed reduction of vessels' number (12. 9+/ 2.3 and 14.8+/-3.3%), neovascularization area (13.1+/-1.7 and 14.3+/-1.7%) and total length of vessels (9.2+/-1.5 and 9.9+/-1.9%). On the other hand, thalidomide did not alter vascularization parameters. Consequently, addition of thiosemicarbazone pharmacophore group into the phthalimidic ring improved the in vivo antitumor and antiangiogenic potential of the analogs 2a and 2b. PMID- 26134002 TI - Delayed pressure urticaria: response to treatment with sulfasalazine in a case series of seventeen patients. AB - We retrospectively identified 17 patients with delayed pressure urticaria (DPU), diagnosed by history and confirmed with provocative pressure testing. The average age in the cohort was 42.6 years with 10 women and seven men. The mean duration of disease before diagnosis was 19.7 months (range, 1-60 months). The diagnosis of DPU was not included in the differential diagnosis of referring physicians and was not a diagnostic consideration in any of seven biopsies obtained. None of the patients responded adequately to treatment with antihistamines, but all 17 responded transiently when treated with either oral or intramuscular steroids. Eleven patients experienced complete or near complete resolution of DPU with treatment with sulfasalazine (SZ). Four patients had a partial response while two were unable to continue therapy because of drug intolerance. SZ appears to be a low cost and effective treatment for DPU. PMID- 26134003 TI - Origin of microglia: current concepts and past controversies. AB - Microglia are the resident macrophages of the central nervous system (CNS), which sit in close proximity to neural structures and are intimately involved in brain homeostasis. The microglial population also plays fundamental roles during neuronal expansion and differentiation, as well as in the perinatal establishment of synaptic circuits. Any change in the normal brain environment results in microglial activation, which can be detrimental if not appropriately regulated. Aberrant microglial function has been linked to the development of several neurological and psychiatric diseases. However, microglia also possess potent immunoregulatory and regenerative capacities, making them attractive targets for therapeutic manipulation. Such rationale manipulations will, however, require in depth knowledge of their origins and the molecular mechanisms underlying their homeostasis. Here, we discuss the latest advances in our understanding of the origin, differentiation, and homeostasis of microglial cells and their myelomonocytic relatives in the CNS. PMID- 26134006 TI - [ITD mutation burden for the prognosis in FLT3-ITD positive acute myeloid leukemia patients]. AB - OBJECTIVE: To explore the impact of ITD mutation characteristics on the overall survival (OS) and complete remission duration (CRD) in FLT3-ITD positive non-M3 acute myeloid leukemia (AML). METHODS: Capillary electrophoresis was used to detect the FLT3-ITD characteristics after PCR amplication. Single or multiple mutations were identified by the numbers of peak. FLT3-ITD mutation burden was calculated by the peak area of mutant divided by the wild-type and mutant peak areas. Clinical data was collected and followed up in the FLT3-ITD mutation patients. RESULTS: Multiple ITD mutations were common in patients aged 60 and above. Patients with single ITD mutation had higher percentage of blasts in bone marrow than multiple ITD mutations (0.758 vs 0.638, P=0.028). The numbers and length of FLT3-ITD mutation had no impact on prognosis. Patients with less than 10% of ITD mutation burden showed no difference with the intermediate-risk c-kit group in OS and CRD, but the two groups had longer OS and CRD than ITD mutation burden above 10% (OS: undefined, undefined, 9.9 months, P<0.05; CRD: undefined, undefined, 6.7 months, P<0.05). In patients with ITD mutation burden above 10%, cases with NPM1 or CEBPA mutation alone had markedly longer CRD than ITD mutation alone (25.0 vs 5.1 months, P=0.003), while OS were similar (11.4 vs 8.0 months, P>0.05). CONCLUSION: Non-M3 AML patients with less than 10% FLT3-ITD mutation burden had a better prognosis than those above 10%. PMID- 26134005 TI - MetaDiff: differential isoform expression analysis using random-effects meta regression. AB - BACKGROUND: RNA sequencing (RNA-Seq) allows an unbiased survey of the entire transcriptome in a high-throughput manner. A major application of RNA-Seq is to detect differential isoform expression across experimental conditions, which is of great biological interest due to its direct relevance to protein function and disease pathogenesis. Detection of differential isoform expression is challenging because of uncertainty in isoform expression estimation owing to ambiguous reads and variability in precision of the estimates across samples. It is desirable to have a method that can account for these issues and is flexible enough to allow adjustment for covariates. RESULTS: In this paper, we present MetaDiff, a random effects meta-regression model that naturally fits for the above purposes. Through extensive simulations and analysis of an RNA-Seq dataset on human heart failure, we show that the random-effects meta-regression approach is computationally fast, reliable, and can improve the power of differential expression analysis while controlling for false positives due to the effect of covariates or confounding variables. In contrast, several existing methods either fail to control false discovery rate or have reduced power in the presence of covariates or confounding variables. The source code, compiled JAR package and documentation of MetaDiff are freely available at https://github.com/jiach/MetaDiff. CONCLUSION: Our results indicate that random-effects meta-regression offers a flexible framework for differential expression analysis of isoforms, particularly when gene expression is influenced by other variables. PMID- 26134004 TI - Transcriptional and Epigenetic Regulation of Oligodendrocyte Development and Myelination in the Central Nervous System. AB - Central nervous system (CNS) myelination by oligodendrocytes (OLs) is a highly orchestrated process involving well-defined steps from specification of neural stem cells into proliferative OL precursors followed by terminal differentiation and subsequent maturation of these precursors into myelinating OLs. These specification and differentiation processes are mediated by profound global changes in gene expression, which are in turn subject to control by both extracellular signals and regulatory networks intrinsic to the OL lineage. Recently, basic transcriptional mechanisms that control OL differentiation and myelination have begun to be elucidated at the molecular level and on a genome scale. The interplay between transcription factors activated by differentiation promoting signals and master regulators likely exerts a crucial role in controlling stage-specific progression of the OL lineage. In this review, we describe the current state of knowledge regarding the transcription factors and the epigenetic programs including histone methylation, acetylation, chromatin remodeling, micro-RNAs, and noncoding RNAs that regulate development of OLs and myelination. PMID- 26134007 TI - [Clinical analysis of 25 patients with aggressive peripheral T-cell lymphoma in advanced stage treated with autologous stem cell transplantation]. AB - OBJECTIVE: To investigate the outcomes of autologous stem cell transplantation (ASCT) for patients with aggressive peripheral T-cell lymphoma (PTCLs) in advanced stage. METHODS: The clinical data of 25 patients in complete remission (CR) with aggressive PTCLs received ASCT from May 1997 to June 2013 were retrospectively analyzed. RESULTS: 1 Of the 25 cases, 16 were unspecified PTCL (PTCL-U), 4 with angioimmunoblastic T cell lymphoma (AITL), 3 with anaplastic large cell lymphoma (ALCL) and 2 with hepatosplenic T cell lymphoma (HSTL), with a median age of 30(12-54) years old. Ratio of male to female is 16?9. The distribution of stages was 8 cases with stage III and 17 patients with stage IV. Nine patients presented with bone marrow involvement. Before ASCT, 18 patients were in CR1 and 7 patients were in CR2. 2Two patients with HSTL in stage IVB and IPI score 4/5 in CR1 relapsed and died within 12 months after ASCT. At a median follow-up of 38 (range 14-110) months, the estimated 3-year probability of PFS and OS for the other 23 patients was (63.1 +/- 10.5)% and (71.8 +/- 9.9)%, respectively. The patients in first CR had a better survival than the patients in second CR. The 3-year probability of PFS were (74.9 +/- 11.0)% vs (33.3 +/- 19.2)% (P=0.092) and OS were (80.2 +/- 10.4)% vs (50.0 +/- 20.4)% (P=0.043), respectively. The 3-year probability of PFS and OS were (40.0 +/- 17.4)% and (53.3 +/- 17.3)% in bone marrow involvement patients and the corresponding figure were (77.9 +/- 11.3)% and (84.4 +/- 10.2)% in non- bone marrow involvement patients. CONCLUSION: ASCT could improve the survival of aggressive PTCLs. Non CR1 status and bone marrow involvement had negative influence on OS in patients with aggressive PTCLs treated by ASCT. The prognosis was very poor in patients with HSTL and satisfactory regimens should be investigated. PMID- 26134008 TI - [Effects of stromal cells on sentitivity to imatinib in Sup-B15 Philadelphia chromosome positive acute lymphoblastic leukemia cells]. AB - OBJECTIVE: To investigate the sensitivity of imatinib (IM) on Sup-B15 Ph+ acute lmphoblastic leukemia (ALL) cells indused by stromal cells OP9, and to further explore its mechanism. METHODS: The study is divided into two group, Sup-B15 cells group and co-cultured with OP9 cells group (Sup-B15/OP9 group). The inhibitory effects of IM on leukemia cells were measured by CCK-8 test, and the apoptosis by Annexin V/7-AAD dyeing and the percentage of CD 34+CD38- leukemia cells were determined by flow cytometry. ALDH1, CD144, and beta-catenin mRNA were detected by real-time RT-PCR, protein levels by Western blot. Inmunoprecipitation was used to detect the level of beta-catenin connected to CD144. RESULTS: IM presented inhibitory effects on Sup-B15 and Sup-B15/OP9 cells at multiple concentrations from 10 MUmol/L to 45 MUmol/L. The IC50 of IM on Sup-B15/OP and Sup-B15 cells were 35.8 MUmol/L and 6.3 MUmol/L, respectively (P<0.05). After 24 h of 30 MUmol/L IM treatment, the percentages of apoptosis cells in Sup-B15/OP9 and Sup-B 15 cell were (14.24 +/- 2.11)% and (3.45 +/- 0.68)%, respectively (P<0.05). The percentage of CD34+CD38- cells in Sup-B15/OP9 group was significantly higher than that in Sup-B15 group [(3.42 +/- 0.28)% vs (0.16 +/- 0.15)%, P<0.05]. As compared to Sup-B15 cells, the transcription of ALDH1 in Sup B15/OP9 group was remarkably upregulated (0.097 +/- 0.012 vs 0.046 +/- 0.010, P<0.05), and the CD133 protein level was also upregulated in Sup-B15/OP9 group. The transcription of CD144 in Sup-B15/OP9 group was remarkably upregulated compared with Sup-B15 group (0.103 +/- 0.015 vs 0.010+/-0.003, P<0.05), as well as the CD144 protein. beta-catenin mRNA transcription has no obvious changes between Sup-B15 group and Sup-B15/OP9 group (P>0.05), while the whole beta catenin protein and the cell nucleus beta-catenin significantly increased, as well as the beta-catenin protein combined with CD144. CONCLUSION: Co-cultured with OP9 cells, Sup-B15 cells show less sensitivity to imatinib. The raising activity of CD144 and CD144/beta-catenin signaling may work in this procession. PMID- 26134009 TI - [Involvement of oxidative stress in embelin-induced cell death in leukemia HL-60 cells]. AB - OBJECTIVE: To evaluate the effects of Embelin on HL-60 cells by the impact of oxidative stress on DNA double-strain breaks (DSBs). METHODS: HL-60 cells were treated with Embelin in different concentration (3, 10, 30, 100, and 300 MUg/ml) for 24 h, and inhibitory effects was examined by CCK-8 assay. Reactive oxygen species (ROS) levels were evaluated by flow cytometry using DCFH-DA. Comet assay was used to detect the extent of DSBs. RESULTS: Embelin inhibited proliferation of HL-60 cells in a dose-dependent manner. At the concentration of 10, 30, 100, and 300 MUg/ml, the inhibition rate was (12.74 +/- 2.27)%, (23.49 +/- 1.96)%, (30.30+/-1.89)%, and (57.55 +/- 3.59)% (P<0.05). Embelin also lead to high level of intracellular ROS and deterioration of DNA damage (P<0.05). When HL-60 cells were pretreated with ROS scavenger N-acetyl-l-cysteine (NAC) for 2 h and then treated with 300 MUg/ml Embelin for 24 h, the intracellular ROS level declined and DSBs relieved (P<0.05). Meanwhile, embelin-induced cell viability significantly declined to (32.75 +/- 2.70)% (P<0.05). CONCLUSION: Embelin induced the death of HL-60 cells by increasing the generation of intracellular oxidation and the oxidative stress, which drived the damage of DNA double-strand. PMID- 26134010 TI - [Vascular endothelial injury induced by anti-endothelial cell antibody in allogeneic hematopoietic stem cell transplantation]. AB - OBJECTIVE: To clarify the role of endothelial cells (ECs) injury induced by anti endothelial cell antibody (AECA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Serum immunoglobulin (IgG) from allo-HSCT recipients were purified and incubated with human umbilical vein vascular endothelium (HUVEC) in vitro, then the functional changes and cell apoptosis were tested. RESULTS: After incubation with AECA positive IgG, soluble adhesion molecules significantly elevated in culture supernatant. When concentration of IgG was 160, 320, and 640 MUg/ml, concentrations of soluble intercellular adhesion molecule-1 in supernatant were statistically higher in AECA positive groups [(117.10 +/- 12.82) vs (78.17 +/- 4.90) pg/ml, (151.30 +/- 15.35) vs (89.46 +/- 6.02) pg/ml, (239.00 +/- 32.53) vs (127.80 +/- 13.86) pg/ml, P<0.01)]. When concentration of IgG was 40, 80, 160, 320, and 640 MUg/ml, concentrations of soluble vascular cell adhesion molecule-1 in supernatant were also statistically higher in AECA positive groups [(38.51 +/- 3.76) vs (24.78 +/- 2.59) pg/ml, (61.34 +/- 6.99) vs (38.20 +/- 3.17) pg/ml, (135.60 +/- 24.46) vs (63.73 +/- 5.08) pg/ml, (221.30 +/- 29.40) vs (112.80 +/- 8.91) pg/ml, (420.90 +/- 31.70) vs (224.40 +/- 20.79) pg/ml, P<0.01]. Clotting activity factors also elevated in culture supernatant after incubation with AECA positive IgG. When concentration of IgG was 80, 160, 320, and 640 MUg/ml, concentrations of von Willebrand factor were statistically higher in AECA positive groups [(19.51 +/- 0.72) vs (17.17 +/- 0.60) ng/ml, P=0.0193; (22.97 +/- 1.18) vs (18.27 +/- 0.61) ng/ml, (26.40 +/- 1.54) vs (19.53 +/- 0.70) ng/ml, (34.35 +/- 1.60) vs (23.81 +/- 0.92) ng/ml, P<0.01]. When concentration of IgG was 320 and 640 MUg/ml, concentrations of thrombomodulin were statistically higher in AECA positive groups [(57.50 +/- 4.50) vs (40.31 +/- 4.39) pg/ml, P=0.0132; (59.18 +/- 4.11) vs (38.84 +/- 5.16) pg/ml, P<0.01]. However, inflammatory factors (IL-1beta, IL-6, IL-8 and ANG2) were not statistically different in AECA positive and negative groups (P>0.05). Moreover, IgG from AECA positive samples did not change the proliferation or cell apoptosis. CONCLUSION: AECA from allo-HSCT recipients dysregulates ECs' function in vitro, but do not induce apoptosis, which is valuable in the pathophysiology of graft-versus-host disease (GVHD) and other complications after allo-HSCT. PMID- 26134011 TI - [Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT]. AB - OBJECTIVE: To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). METHODS: A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. RESULTS: All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of II-IV degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 +/- 7.8)%, (66.7 +/- 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. CONCLUSION: Bu/ID-Flu conditioning regimen for MDS and MDS AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application. PMID- 26134012 TI - [Autologous hematopoietic stem cell transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: a single center experience from the BDHALL2000/02 protocol]. AB - OBJECTIVE: To evaluate the results of autologous hematopoietic stem cell transplantation (auto-HSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL). METHODS: From January 2000 to December 2007, the clinical data of auto-HSCT in adults Ph-ALL with complete remession (CR) 1 according to BDHALL2000/02 protocol were analyzed. RESULTS: A total of 56 patients were enrolled and the probabilities of standard risk, intermediated risk and high-risk group were 41.1%, 33.9%, and 25.0%, respectively. After a median follow-up of 75 months (range 7-177 months), the 5-year overall survival (OS), events free survival (EFS) and relapse free survival (RFS) were (51.8 +/- 6.7)%, (51.8 +/- 6.7)%, and (60.5 +/- 6.9)%, respectively. And the 5-year accumulative relapse rate was (39.1 +/- 6.9)%. The 5-year OS of standard risk, intermediate risk, high-risk group were (60.9 +/- 10.2)%, (52.6 +/- 11.5)%, and (35.7 +/- 2.8)%, respectively. The 5-year RFS among three groups were (68.3 +/- 9.9)%, (62.5 +/- 12.1)%, and (44.9 +/- 14.1)%, respectively. The 5-year EFS among three groups were (60.9 +/- 10.2)%, (52.6 +/- 11.5)%, and (35.7 +/- 12.8)%, respectively. The 5-year accumulative relapse rate among three groups were (31.7 +/- 9.9)%, (37.5 +/- 12.1)%, and (55.1 +/- 14.1)%, respectively. There was no statistical significance of any survival rates between standard and intermediate risk groups, just as intermediate and high-risk groups. The OS and EFS in standard risk group were superior to those in high-risk group (P=0.040 and P=0.029, respectively), while there was no statistical significance of RFS and accumulative relapse rate between the two groups. The clinical factors listed below did not influenced the prognosis in the univariate analysis (P>0.05), including more than 5 weeks reaching to CR, WBC count at diagnosis, different immunophenotype (T or B cells), myeloid antigen expression, hyperdiploid chromosome karyotype, complex chromosome abnormality, conditioning regimen with or without TBI, duration between transplantation and diagnosis. CONCLUSION: Ph ALL adults could achieve a satisfactory CR and better survial according to BDHALL2000/02 protocol followed by auto-HSCT, especially for the standard or intermediate risk group, and no-donors high-risk patients. PMID- 26134013 TI - [Inhibitory effects of Hes1 on acute myeloid leukemia cells]. AB - OBJECTIVE: To elucidate the impact of Hes1 on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. METHODS: The expression levels of Hes1 and p21 in AML patient samples and myeloid leukemia cell lines were analyzed by real time PCR. Hes1 was up-regulated by retrovirus transfection in AML cell lines and the proliferation capacity were assayed by MTT, cell cycle by Hoechst/PY, apoptosis by AnnexinV. RESULTS: The expression of Hes1 in primary AML cells and HL-60, U937, KG1a cell lines were 0.67 +/- 0.24, 0.59 +/- 0.43, 0.42 +/- 0.03, and 0.32 +/- 0.26, respectively, and p21 were 0.54 +/- 0.01, 0.44 +/- 0.12, 0.36 +/- 0.12, and 0.59 +/- 0.43, respectively. Hes1 expression levels after transduction in HL-60, U937, KG1a were 4.9 +/- 0.2, 5.2 +/- 0.4, 5.8 +/- 0.5, respectively. Induced activation of Hes1 led to AML cells growth arrest and apoptosis, which was associated with an enhanced p21 expression. Besides, activated Hes1 led to AML cells growth inhibition in vivo. CONCLUSION: Hes1 could mediate growth arrest and apoptosis in AML cells, which may be a novel target for AML. PMID- 26134014 TI - [Diagnostic value of three evaluation methods of 18F-FDG PET/CT in detecting bone marrow infiltration in patients with newly diagnosed diffuse large B-cell lymphoma]. AB - OBJECTIVE: To evaluate three methods of 18F-FDG PET/CT in detecting bone marrow infiltration in patients with newly diagnosed diffuse large B-cell lymphoma. METHODS: Seventy-seven patients with newly diagnosed diffuse large B-cell lymphoma from July 2012 to June 2014 were retrospectively analyzed. All patients received both 18F-FDG PET/CT scan and bone marrow biopsy in the region of the posterior iliac crests. There were three evaluation methods of 18F-FDG PET/CT to detect bone marrow infiltration, including visual comparison (the FDG uptake in bone marrow of iliac crests was higher than the normal liver tissue), the maximal standardized uptake values (SUV(max)) in bone marrow of iliac crests (more than or equal to 2.5), the ratio of maximal standardized uptake values of iliac crests bone marrow to liver parenchyma intensity (more than 1). All results were compared with the bone marrow biopsy. RESULTS: Visual comparison of 18F-FDG PET/CT could be used to diagnose bone marrow infiltration, with the sensitivity of 100.00%, specificity of 80.00%, positive predictive value of 48.00%, and negative predictive value of 100.00%. When the SUV(max) of iliac crests was used as the diagnostic threshold, the sensitivity was 75.00%, with 92.31% specificity, 64.29% positive predictive value, and 95.24% negative predictive value. The ratio of SUV(max) had the best diagnostic efficiency, with sensitivity of 100.00%, specificity of 90.77%, positive predictive value of 66.67%, and negative predictive value of 100.00%. CONCLUSION: The ratio of SUV(max) is a valuable diagnostic method in detecting diffuse large B-cell lymphoatic bone marrow involvement. PMID- 26134015 TI - [Clinical and biological characteristics of non-IgM lymphoplasmacytic lymphoma]. AB - OBJECTIVE: To observe the clinical and biological characteristics of Non-IgM secreting lymphoplasmacytic lymphoma (LPL) and draw the differences between non IgM LPL and Waldenstrom macroglobulinemia (WM). METHODS: Records of 13 patients with non-IgM LPL were retrospectively analyzed between January 2000 and December 2013. The cytogenetic aberrations were detected by fluorescence in situ hybridisation (FISH). RESULTS: In the cohort, 7 males and 6 females with a median age of 63 years (range 43 to 74), two patients were IgA secreting, 6 with IgG secreting and 5 patients without monoclonal globulin. The major complaint at diagnosis included anemia associated symptom (53.8%), mucocutaneous hemorrhage and superficial lymphadenopathy (15.4%). Eight patients had B symptom at diagnosis. All of the 13 patients had bone marrow involvement and anemia, and 10 patients had 2 or 3 lineage cytopenia. In 5 patients with available immunophenotypic data, all expressed CD19, CD20, CD22 and CD25, but missed the expression of CD10, CD103 and CD38. Two cases had CD5 or sIgM positive alone. Another 2 patients were CD23 or CD11c positive and 3 patients were FMC7 positive. Cytogenetic aberrations had been detected by FISH in 7 patients, but only two (28.6%) patients had aberrations with del(6q). CONCLUSION: The clinical and biological characteristics had no significantly difference between non-IgM LPL and WM. PMID- 26134016 TI - [Cytotoxity of pomalidomide combined CAR-T cell for multiple myeloma cell RPMI8226 and U266]. AB - OBJECTIVE: To observe the cytotoxity of CD138-CAR-T cells on human multiple myeloma cell RPMI8226 and U266 cells and explore the impact of pomalidomide on the cytotoxity of CD138-CAR-T on RPMI8226 and U266 cells. METHODS: The cytotoxity of CD138-CAR-T and CD138-CAR-T combined pomalidomide on RPMI8226 and U266 was detected by CFSE/7AAD. The effctor cells were co-cultured with target cells at 5:1 for 18 h, and then the supernatant were collected and used for ELISA assays. RESULTS: After 18 h co-culture, the cytotoxity of CD138-CAR-T on RPMI8226 and U266 was significantiy higher than control (P<0.01). There was no significant change on the cytotoxity of pomalidoide combined with CD138-CAR-T on RPMI8226 and U266. The results showed that co-cultured system contribted to a markedly increased production of IFN-gamma, after adding pomalidomide to the co-cultured system. It can significantly enhance the production of IFN-gamma, compared with CD138-CAR-T alone. CONCLUSION: CD138-CAR-T had significantly cytotoxity on U266 and RPMI8226. Pomalidomide could promote CD138-CAR-T cells IFN-gamma production. PMID- 26134017 TI - [Clinical analysis of multiple myeloma patients with bone-related extramedullary disease: a longitudinal study on 834 consecutive patients in a single center of China]. AB - OBJECTIVE: To analyse the incidence, clinical features, prognosis of bone-related extramedullary disease (bEMD) and its relationship with strict EMD (sEMD) in MM patients. METHODS: The records of 834 consecutive newly diagnosed patients with MM in our hospital between 1993 and 2013 were retrospectively reviewed. RESULTS: 1Among 834 patients at diagnosis, 32 cases (3.8%) showed bEMD, and 40 cases (4.8%) showed sEMD. Patients with bEMD at presentation showed significant lower level of lactate dehydrogenase (180.9 U/L vs 299.2 U/L, P=0.034) and higher overall response rate (ORR) (95.7% vs 66.7%, P=0.009) compared with sEMD patients. While the above two parameters were comparable between patients with bEMD and without EMD. 2As to the prognosis of patients without autologous hematopoietic stem cell transplantation (auto-HSCT), the overall survival (OS) of patients with sEMD, bEMD and without EMD was 14.0, 37.5, and 38.0 months, respectively. The time to progression (TTP) of the three groups was 11.5, 27.0, and 22.0 months, respectively. Compared to the patients with sEMD, the outcomes (both OS and TTP) of the other two groups was significantly better (P<0.05). Patients with bEMD at presentation was comparable to the patients without EMD, but the two groups were better than the patients with sEMD. 3The incidence of bEMD during follow-up was 0.5%. The OS of patients with sEMD, bEMD and without EMD during follow-up was 26.0, 17.0, and 40.0 months, respectively. The TTP of the three groups was 13.0, 11.0, and 25.0 months, respectively. The outcomes (both OS and TTP) of patients with bEMD at relapse/progression showed no significant difference as compared with the other two groups (P>0.05). CONCLUSION: The clinical features of MM patients with bEMD are different from the patients with sEMD. Outcomes of this population is significantly better than the latter, and is comparable to the patients without EMD. It suggests that bEMD alone has no negative prognostic significance in MM patients. PMID- 26134018 TI - [Treatment outcomes and prognostic analysis of 61 Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis]. AB - OBJECTIVE: To investigate the outcomes, survival status, and the prognostic factors of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV HLH) patients. METHODS: A retrospective study was carried out to analyze the clinical data of 61 EBV-HLH cases, from January 2008 to July 2014. Prognostic factors were analyzed through COX model (single factor and multiple factors). RESULTS: A total of 246 patients with HLH were diagnosed, among which 102 cases were with EBV infection (including 61 EBV-HLH, 36 lymphoma associated HLH, 5 primary HLH. Among the 61 cases, 40 were male and 21 were female, with a ration of 1.9:1. The median age was 28 years (range, 12-78). 1, 3, 6 and 12-month overall survival rates of 61 EBV-HLH were 65.6%, 47.5%, 32.4%, and 25.0%, respectively. The median follow-up time was 3 (0.5-28) months. 12 patients didn't use etoposide within 4 weeks after diagnosis, while HLH-94 protocol was used in 33 patients and HLH-2004 protocol was used in 16 patients. Response rates of theses three groups were 33.3%, 51.5%, and 43.8%, respectively (P=0.401). There was statistically difference between the group without etoposide and the HLH-94/ HLH-2004 group in the overall survival rate (P=0.033). Serum albumin level (P=0.033) and whether EBV could became negative (P=0.010) were independent predictors for EBV-HLH. CONCLUSION: EBV-HLH patients have severe clinical feature and poor prognosis. Early application of immune chemotherapy based on etoposide can improve survival. Serum albumin level and whether EBV can become negative are independent prognostic factors for survival. PMID- 26134019 TI - [Efficacy and safety of rhTPO in the treatment of pediatric primary immune thrombocytopenia]. AB - OBJECTIVE: To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treatment of pediatric primary immune thrombocytopenia (ITP). METHODS: The clinical characteristics of 41 pediatric ITP patients who received rhTPO therapy from December 2006 to September 2014 were retrospectively analyzed (as rhTPO group). During the same time another 26 pediatric ITP patients who received vindesine combined with human immunoglobulin therapy were selected as control group. The treatment outcomes were evaluated. RESULTS: A total of 67 cases of pediatric ITP, 31 males and 36 females with a median age 10.0(1.6-17.0) years were enrolled, including 19 cases of newly disgnosed ITP, 18 cases of persistent ITP and 30 cases of chronic ITP. Of them, 43 cases of whom were severe ITP (PLT<10*109/L). The total response rate had no statistically significant difference between the rhTPO group and the control group (68.29% vs 65.38%, P=0.806), neither in newly ITP, persistent and chronic ITP (P=0.320, P=0.763). In severe ITP patients, 17 of 30 cases (56.67%) achieved response with rhTPO therapy, while the control group was 61.54% (8/13) (P=0.766). The median maximum peak of platelet counts and the time of the platelet counts >30*109/L and > 50*109/L had no statistically significant differences in rhTPO group compared with the control group [52(7-608)*109/L vs 40(3-152)*109/L, P=0.05; 7(3-13) d vs 4(2-24) d, P=0.202; 7.5(4-15) d vs 5.5(4-23) d, P=0.557]. The mean platelet counts were 43(3-605)*109/L in the rhTPO group, which were higher than the control group [32(-14-149)*109/L, P=0.042]. No severe adverse effects were observed in both groups. CONCLUSION: For pediatric ITP, rhTPO has a similar outcomes with vindesine combined with human immunoglobulin, and it is an effective and safe treatment option. PMID- 26134020 TI - [Study on C5b-9 deposited on the membrane of platelets and its dysfunction in patients with paroxysmal nocturnal hemoglobinuria]. AB - OBJECTIVE: To explore the expression levels of terminal complement complex (C5b 9) and CD62p on platelets and the soluble C5b-9 (sC5b-9) level in serum in patients with PNH or PNH-aplastic anemia (AA). METHODS: Serum levels of sC5b-9, complement C3 and C4 were detected by using ELISA in 25 patients with PNH/PNH-AA. The quantities of C5b-9 and CD62p on the membrane of platelets were detected by flow cytometry. RESULTS: 1In PNH/PNH-AA group, the serum sC5b-9 level [390.27(265.73-676.87) MUg/L] was lower than that in control group [540.39(344.20 1 576.78) MUg/L] (P<0.01). 2The platelet PNH clone (CD59-CD61+/CD61+) size [50.58(23.29-81.60)%] was bigger in the PNH/PNH-AA group than that [23.57(15.58 29.02)%] in control group (P<0.01). The percentages of C5b-9 deposition (C5b 9+CD61+/CD61+) were higher on the PNH clone platelets (CD59-CD61+) in the PNH/PNH AA group [(17.53 +/- 6.27)%] than those on the normal platelets (CD59+CD61+) in PNH patients 11.33+/-5.03)%] and control [(10.88+/-3.58)%] group (P<0.01). 3 The expression of CD62p (CD62p+CD61+/CD61+) on PNH clone platelets in PNH patients [(61.98 +/- 11.71)%] was higher than that on the normal platelets in PNH patients [(43.76+/-11.30)%] and control group [(38.23+/-18.07)%] (P<0.01). In addition, the expression of CD62p on normal platelets was higher in PNH patients than control (P<0.05). 4The deposition of C5b-9 positively correlated with the expression of CD62p on the platelets (r=0.559, P=0.002). CONCLUSION: Deficiency of CD59 antigen on platelets in PNH patients may lead to the deposition of C5b-9 on its membrane and its dysfunction, which may contribute to thrombosis events in PNH. PMID- 26134021 TI - [The impact of autophagy on proliferation of HEL cells and hematopoietic cells of polycythemia vera patients with JAK2 V617F mutation]. AB - OBJECTIVE: To detect the activity of autophagy and explore the impact on survival and proliferation of HEL cells and hematopoietic cells of polycythemia vera (PV) patients with JAK2 V617F mutation. METHODS: Flow cytometry, AO staining and Western blot methods were used to detect the autophagy activity and the expression of LC3-II protein of JAK2 V617F+ HEL cells and hematopoietic cells of 12 newly diagnosed PV patients with JAK2 V617F mutation. HEL cells and bone marrow cells of 3 PV patients were treated with rapamycin or 3-MA to induce and inhibit autophagy, respectively. CellTiter Glo(R) method was used to detect the proliferation activity of cells. RESULTS: There was higher level of mean LC3-II fluorescence intensity in HEL cells (159 389 +/- 29 001) than that in K562 cells (96 047 +/- 24 134) (P=0.044). The formation of autophagosome in HEL cells is more than that in K562 cells detected by microscope. What's more, the level of mean LC3-II fluorescence intensity in 12 PV patients' myeloid cells (92 842 +/- 4 250) was higher than that of 15 healthy volunteers (86 633 +/- 2 504) (P=0.001). The expression of LC3-II protein was higher in PV patients' peripheral blood cells than that in healthy volunteers detected by Western blot. After treated with rapamycin 12, 24, 48 h, the activity of autophagy in HEL cells and bone marrow cells of 3 PV patients were increased and the proliferation activity was higher than the control group, the proliferation activity at 48 h were (101 413 +/- 3 720), (18 744 +/- 1 015), respectively. However, after treated with 3-MA 12, 24, 48 h, the activity of autophagy was decreased and the proliferation activity was lower than the control group, the proliferation activity at 48 h were (5 732 +/- 166), (5 371 +/- 56), respectively. CONCLUSION: There is high basical activity of autophagy in JAK2 V617F+ HEL cells and hematopoietic cells of PV patients with JAK2 V617F mutation. Up-regulated autophagy promotes proliferation of JAK2 V617F+ HEL cells and bone marrow cells of PV patients with JAK2 V617F mutation. Decreased autophagy inhibits proliferation of JAK2 V617F+ HEL cells and bone marrow cells of PV patients with JAK2 V617F mutation. PMID- 26134022 TI - [Expression of human mutT homologue 1 (hMTH1) and its clinical significance in acute lymphoblastic leukemia]. PMID- 26134023 TI - [Asian variant of intravascular large B cell lymphoma with leukemia:a case report and literature review]. PMID- 26134024 TI - [Unrelated cord blood transplantation in the treatment of paroxysmal nocturnal hemoglobinuria: a case report and literature review]. PMID- 26134025 TI - [Intermittent and spontaneous gingival hemorrhage and purpura]. PMID- 26134026 TI - [T-cell prolymphocytic leukemia treated with alemtuzumab and followed by autologous hematopoietic stem cell transplantation: a case report]. PMID- 26134027 TI - Effects on health of air pollution: a narrative review. AB - Air pollution is a complex and ubiquitous mixture of pollutants including particulate matter, chemical substances and biological materials. There is growing awareness of the adverse effects on health of air pollution following both acute and chronic exposure, with a rapidly expanding body of evidence linking air pollution with an increased risk of respiratory (e.g., asthma, chronic obstructive pulmonary disease, lung cancer) and cardiovascular disease (e.g., myocardial infarction, heart failure, cerebrovascular accidents). Elderly subjects, pregnant women, infants and people with prior diseases appear especially susceptible to the deleterious effects of ambient air pollution. The main diseases associated with exposure to air pollutants will be summarized in this narrative review. PMID- 26134029 TI - L-type amino acid transporter-1 and CD98 expression in bone and soft tissue tumors. AB - L-type amino acid transporter-1 (LAT1) is expressed in many cancers. We examined LAT1 and CD98 expression immunohistochemically in surgically resected specimens of various bone and soft tissue tumors. Out of 226 cases, 79 (35%) were LAT1(+) and 95 (42%) were CD98(+) . In bone tumors, LAT1 was highly expressed in osteoblastoma (89%), chondrosarcoma (50%), and osteosarcoma (60%); in soft tissue tumors, LAT1 was highly expressed in rhabdomyosarcoma (80%), synovial sarcoma (63%), Ewing's sarcoma (60%), epithelioid sarcoma (100%) and angiosarcoma (100%). In malignant soft tissue tumors, LAT1 expression was associated with higher histological grade. High CD98 expression was seen in many bone tumors of intermediate and high malignancy. Among soft tissue tumors, CD98 was expressed in tendon sheath giant cell tumor and malignant peripheral nerve sheath tumor (57%), Ewing's sarcoma (50%) and undifferentiated sarcoma (64%). Some of the malignant soft tissue tumors expressed both LAT1 and CD98. This study showed that LAT1 and CD98 was expressed in many malignant and intermediate bone tumors, and some malignant soft tissue tumors. PMID- 26134030 TI - Which terms should be used to describe autism? Perspectives from the UK autism community. AB - Recent public discussions suggest that there is much disagreement about the way autism is and should be described. This study sought to elicit the views and preferences of UK autism community members - autistic people, parents and their broader support network - about the terms they use to describe autism. In all, 3470 UK residents responded to an online survey on their preferred ways of describing autism and their rationale for such preferences. The results clearly show that people use many terms to describe autism. The most highly endorsed terms were 'autism' and 'on the autism spectrum', and to a lesser extent, 'autism spectrum disorder', for which there was consensus across community groups. The groups disagreed, however, on the use of several terms. The term 'autistic' was endorsed by a large percentage of autistic adults, family members/friends and parents but by considerably fewer professionals; 'person with autism' was endorsed by almost half of professionals but by fewer autistic adults and parents. Qualitative analysis of an open-ended question revealed the reasons underlying respondents' preferences. These findings demonstrate that there is no single way of describing autism that is universally accepted and preferred by the UK's autism community and that some disagreements appear deeply entrenched. PMID- 26134028 TI - Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. AB - Bile acids are signalling molecules, which activate the transmembrane receptor TGR5 and the nuclear receptor FXR. BA sequestrants (BAS) complex bile acids in the intestinal lumen and decrease intestinal FXR activity. The BAS-BA complex also induces glucagon-like peptide-1 (GLP-1) production by L cells which potentiates beta-cell glucose-induced insulin secretion. Whether FXR is expressed in L cells and controls GLP-1 production is unknown. Here, we show that FXR activation in L cells decreases proglucagon expression by interfering with the glucose-responsive factor Carbohydrate-Responsive Element Binding Protein (ChREBP) and GLP-1 secretion by inhibiting glycolysis. In vivo, FXR deficiency increases GLP-1 gene expression and secretion in response to glucose hence improving glucose metabolism. Moreover, treatment of ob/ob mice with the BAS colesevelam increases intestinal proglucagon gene expression and improves glycaemia in a FXR-dependent manner. These findings identify the FXR/GLP-1 pathway as a new mechanism of BA control of glucose metabolism and a pharmacological target for type 2 diabetes. PMID- 26134032 TI - Effect of N-n-butyl haloperidol iodide on ROS/JNK/Egr-1 signaling in H9c2 cells after hypoxia/reoxygenation. AB - Reactive oxygen species (ROS)-induced oxidative stress in cells is an important pathophysiological process during myocardial ischemia/reperfusion (I/R) injury, and the transcription factor Egr-1 is a master switch for various damage pathways during reperfusion injury. An in vitro model of myocardial I/R injury and H9c2 cardiomyoblast cells hypoxia/reoxygenation (H/R) was used to assess whether there is abnormal intracellular ROS/JNK/Egr-1 signaling. We also assessed whether N-n butyl haloperidol (F2), which exerts protective effects during myocardial I/R injury, can modulate this pathway. H/R induced ROS generation, JNK activation, and increased the expression of Egr-1 protein in H9c2 cells. The ROS scavengers edaravone (EDA) and N-acetyl-L-cysteine (NAC) reduced ROS level, downregulated JNK activation, and Egr-1 expression in H9c2 cells after H/R. The JNK inhibitor SP600125 inhibited Egr-1 overexpression in H9c2 cells caused by H/R. F2 could downregulate H/R-induced ROS level, JNK activation, and Egr-1 expression in H9c2 cells in a dose-dependent manner. The ROS donor hypoxanthine-xanthine oxidase (XO/HX) and the JNK activator ANISO antagonized the effects of F2. Therefore, H/R activates ROS/Egr-1 signaling pathway in H9c2 cells, and JNK activation plays an important role in this pathway. F2 regulates H/R-induced ROS/JNK/Egr-1 signaling, which might be an important mechanism by which it antagonizes myocardial I/R injury. PMID- 26134034 TI - The Affordable Care Act and Expanded Insurance Eligibility Among Nonelderly Adult Cancer Survivors. AB - BACKGROUND: Cancer survivors may face barriers to accessing health insurance and experience financial hardship because of medical expenditures. We examined potential improvements in access to insurance for cancer survivors through adult Medicaid expansions and premium tax credits in the new insurance marketplaces under the Affordable Care Act (ACA). METHODS: Eligibility for Medicaid and premium tax credits was simulated for cancer survivors age 18 to 64 years in the 2008 to 2010 Medical Expenditure Panel Survey using a detailed deterministic model. Financial hardship was determined as: 1) delays or unmet need for medical, prescription, or dental care because of cost or insurance issues and/or 2) family out-of-pocket medical spending that was 20% or more of gross income. Descriptive analyses were stratified by whether the state of residence chose to expand Medicaid by January 2015. All statistical tests were two-sided. RESULTS: Overall, 14.7% of 9.44 million cancer survivors were uninsured, with 18% reporting financial hardship. Under the ACA, 19% overall, 30% of the uninsured, and 39% of those reporting financial hardship would be Medicaid eligible. An additional 10% would be eligible for premium tax credits, with the remainder able to participate in the Marketplace without tax credits. However, 21% of uninsured cancer survivors in states not expanding Medicaid would be ineligible for assistance with coverage. CONCLUSIONS: Under the ACA, many of the uninsured and a larger proportion of survivors facing financial hardship will be eligible for Medicaid or premium tax credits in the Marketplaces. ACA implementation will dramatically enhance insurance availability and is likely to reduce financial hardship for vulnerable cancer survivors. PMID- 26134033 TI - Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis. AB - BACKGROUND: Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. METHODS: We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. RESULTS: Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10(-6)). CONCLUSION: This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk. PMID- 26134035 TI - 2015 ACC/HRS/SCAI left atrial appendage occlusion device societal overview. PMID- 26134037 TI - Cell-Free Fetal DNA, Telomeres, and the Spontaneous Onset of Parturition. AB - Multiple previous reports have provided compelling support for the premise that spontaneous parturition is mediated by activation of inflammation-related signaling pathways leading to increased secretion of cytokines and chemokines, the influx of neutrophils and macrophages into the pregnant uterus, increased production of uterine activation proteins (eg, connexin-43, cyclo-oxygenase-2, oxytocin receptors, etc), activation of matrix metalloproteinases, and the release of uterotonins leading to cervical ripening, membrane rupture, and myometrial contractions. The missing link has been the fetal/placental signal that triggers these proinflammatory events in the absence of microbial invasion and intrauterine infection. This article reviews the biomedical literature regarding the increase in cell-free fetal DNA (cffDNA), which is released during apoptosis in the placenta and fetal membranes at term, the ability of apoptosis modified vertebrate DNA to stimulate toll-like receptor-9 (TLR9) leading to increased release of cytokines and chemokines, and the potential "fail-safe" role for the anti-inflammatory cytokine IL-10. This article also reviews the literature supporting the key role that telomere loss plays in regard to increasing the ability of vertebrate (including placental) DNA to stimulate TLR9, and in regard to signaling the onset of apoptosis in the placenta and fetal membranes, thereby providing a biologic clock that determines the length of gestation and the timing for the onset of parturition. In summary, this literature review provides a strong rationale for future research to test the hypothesis that telomere loss and increased cffDNA levels trigger the proinflammatory events leading to the spontaneous onset of parturition in mammals: the "cffDNA/telomere hypothesis." PMID- 26134038 TI - Understanding the light soaking effect of ZnMgO buffer in CIGS solar cells. AB - This study investigated the mechanism underlying the light soaking effect of a ZnMgO buffer in Cu(In,Ga)Se2 (CIGS) solar cells, where the cell efficiency increased with an increase of light soaking time. The ZnMgO buffer layer was deposited by an atomic layer deposition method. With light soaking, the cell efficiency of ZnMgO/CIGS cells increased mainly by the increase of the fill factor and partly by the increase of the open-circuit voltage. With light soaking, the electron carrier concentration of the ZnMgO layer increased and the XPS intensity of the hydroxyl bond in the ZnMgO layer decreased. Based on the above results and the comparison of other buffers in literature, we assumed that the hydrogen atoms broken away from the hydroxyl bond by photon irradiation occupied the interstitial sites of the ZnMgO layer as a donor atom and also passivated the defects at the ZnMgO/CIGS interface. The increase of the fill factor and open circuit voltage was explained based on H doping in the ZnMgO layer and H passivation at the ZnO/CIGS interface. PMID- 26134036 TI - Integrative Analysis Reveals Regulatory Programs in Endometriosis. AB - Endometriosis is a common gynecological disease found in approximately 10% of reproductive-age women. Gene expression analysis has been performed to explore alterations in gene expression associated with endometriosis; however, the underlying transcription factors (TFs) governing such expression changes have not been investigated in a systematic way. In this study, we propose a method to integrate gene expression with TF binding data and protein-protein interactions to construct an integrated regulatory network (IRN) for endometriosis. The IRN has shown that the most regulated gene in endometriosis is RUNX1, which is targeted by 14 of 26 TFs also involved in endometriosis. Using 2 published cohorts, GSE7305 (Hover, n = 20) and GSE7307 (Roth, n = 36) from the Gene Expression Omnibus database, we identified a network of TFs, which bind to target genes that are differentially expressed in endometriosis. Enrichment analysis based on the hypergeometric distribution allowed us to predict the TFs involved in endometriosis (n = 40). This included known TFs such as androgen receptor (AR) and critical factors in the pathology of endometriosis, estrogen receptor alpha, and estrogen receptor beta. We also identified several new ones from which we selected FOXA2 and TFAP2C, and their regulation was confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry (IHC). Further, our analysis revealed that the function of AR and p53 in endometriosis is regulated by posttranscriptional changes and not by differential gene expression. Our integrative analysis provides new insights into the regulatory programs involved in endometriosis. PMID- 26134039 TI - Fusion of CT Angiography or MR Angiography with Unenhanced CBCT and Fluoroscopy Guidance in Endovascular Treatments of Aorto-Iliac Steno-Occlusion: Technical Note on a Preliminary Experience. AB - AIM: To evaluate the feasibility of image fusion (IF) of pre-procedural arterial phase CT angiography or MR angiography with intra-procedural fluoroscopy for road mapping in endovascular treatment of aorto-iliac steno-occlusive disease. MATERIALS AND METHODS: Between September and November, 2014, we prospectively evaluated 5 patients with chronic aorto-iliac steno-occlusive disease, who underwent endovascular treatment in the angiography suite. Fusion image road mapping was performed using angiographic phase CT images or MR images acquired before and intra-procedural unenhanced cone-beam CT. Radiation dose of the procedure, volume of intra-procedural iodinated contrast medium, fluoroscopy time, and overall procedural time were recorded. Reasons for potential fusion imaging inaccuracies were also evaluated. RESULTS: Image co-registration and fusion guidance were feasible in all procedures. Mean radiation dose of the procedure was 60.21 Gycm2 (range 55.02-63.75 Gycm2). The mean total procedure time was 32.2 min (range 27-38 min). The mean fluoroscopy time was 12 min and 3 s. The mean procedural iodinated contrast material dose was 24 mL (range 20-40 mL). CONCLUSIONS: IF gives Interventional Radiologists the opportunity to use new technologies in order to improve outcomes with a significant reduction of contrast media administration. PMID- 26134040 TI - Imaging surveillance programs for women at high breast cancer risk in Europe: Are women from ethnic minority groups adequately included? (Review). AB - Women from ethnic minority groups, including immigrants and refugees are reported to have low breast cancer (BC) screening rates. Active, culturally-sensitive outreach is vital for increasing participation of these women in BC screening programs. Women at high BC risk and who belong to an ethnic minority group are of special concern. Such women could benefit from ongoing trials aimed at optimizing screening strategies for early BC detection among those at increased BC risk. Considering the marked disparities in BC survival in Europe and its enormous and dynamic ethnic diversity, these issues are extremely timely for Europe. We systematically reviewed the literature concerning European surveillance studies that had imaging in the protocol and that targeted women at high BC risk. The aim of the present review was thereby to assess the likelihood that women at high BC risk from minority ethnic groups were adequately included in these surveillance programs. Twenty-seven research groups in Europe reported on their imaging surveillance programs for women at increased BC risk. The benefit of strategies such as inclusion of magnetic resonance imaging and/or more intensive screening was clearly documented for the participating women at increased BC risk. However, none of the reports indicated that sufficient outreach was performed to ensure that women at increased BC risk from minority ethnic groups were adequately included in these surveillance programs. On the basis of this systematic review, we conclude that the specific screening needs of ethnic minority women at increased BC risk have not yet been met in Europe. Active, culturally-sensitive outreach is needed to identify minority women at increased BC risk and to facilitate their inclusion in on-going surveillance programs. It is anticipated that these efforts would be most effective if coordinated with the development of European-wide, population-based approaches to BC screening. PMID- 26134041 TI - Molecular cloning and functional analysis of minipig UDP-glucuronosyltransferase 1A6. AB - 1. UDP-glucuronosyltransferase 1A6 (UGT1A6) plays important roles in the glucuronidation of numerous drugs, environmental pollutants, and endogenous substances. Minipigs have been used as experimental animals in pharmacological and toxicological studies because many of their physiological characteristics are similar to those of humans. The aim of the present study was to examine similarities and differences in the enzymatic properties of UGT1A6 between humans and minipigs. 2. Minipig UGT1A6 (mpUGT1A6) cDNA was cloned by the RACE method, and the corresponding proteins were expressed in insect cells. The enzymatic function of mpUGT1A6 was analyzed by the kinetics of serotonin glucuronidation. 3. Amino acid homology between human UGT1A6 (hUGT1A6) and mpUGT1A6 was 79.9%. The kinetics of serotonin glucuronidation by recombinant hUGT1A6 and mpUGT1A6 enzymes fit the Michaelis-Menten equation. The Km, Vmax, and CLint values of hUGT1A6 were 10.5 mM, 4.04 nmol/min/mg protein, and 0.39 uL/min/mg protein, respectively. The Km value of mpUGT1A6 was similar to that of hUGT1A6, whereas the Vmax and CLint values of mpUGT1A6 were approximately 2-fold higher than those of hUGT1A6. 4. These results suggest that the enzymatic properties of UGT1A6 enzymes are moderately different between humans and minipigs. PMID- 26134042 TI - Antitumor effects of a drug combination targeting glycolysis, glutaminolysis and de novo synthesis of fatty acids. AB - There is a strong rationale for targeting the metabolic alterations of cancer cells. The most studied of these are the higher rates of glycolysis, glutaminolysis and de novo synthesis of fatty acids (FAs). Despite the availability of pharmacological inhibitors of these pathways, no preclinical studies targeting them simultaneously have been performed. In the present study it was determined whether three key enzymes for glycolysis, glutaminolysis and de novo synthesis of FAs, hexokinase-2, glutaminase and fatty acid synthase, respectively, were overexpressed as compared to primary fibroblasts. In addition, we showed that at clinically relevant concentrations lonidamine, 6-diazo-5-oxo-L norleucine and orlistat, known inhibitors of the mentioned enzymes, exerted a cell viability inhibitory effect. Genetic downregulation of the three enzymes also reduced cell viability. The three drugs were highly synergistic when administered as a triple combination. Of note, the cytotoxicity of the triple combination was low in primary fibroblasts and was well tolerated when administered into healthy BALB/c mice. The results suggest the feasibility and potential clinical utility of the triple metabolic targeting which merits to be further studied by using either repositioned old drugs or newer, more selective inhibitors. PMID- 26134043 TI - From "What Is?" to "What Isn't?" Computational Biology. PMID- 26134044 TI - The tRNA(Gly) T10003C mutation in mitochondrial haplogroup M11b in a Chinese family with diabetes decreases the steady-state level of tRNA(Gly), increases aberrant reactive oxygen species production, and reduces mitochondrial membrane potential. AB - Mitochondrial diabetes originates mainly from mutations located in maternally transmitted, mitochondrial tRNA-coding genes. In a genetic screening program of type 2 diabetes conducted with a Chinese Han population, we found one family with suggestive maternally transmitted diabetes. The proband's mitochondrial genome was analyzed using DNA sequencing. Total 42 known nucleoside changes and 1 novel variant were identified, and the entire mitochondrial DNA sequence was assigned to haplogroup M11b. Phylogenetic analysis showed that a homoplasmic mutation, 10003T>C transition, occurred at the highly conserved site in the gene encoding tRNA(Gly). Using a transmitochondrial cybrid cell line harboring this mutation, we observed that the steady-state level of tRNA(Gly) significantly affected and the amount of tRNA(Gly) decreased by 97%, production of reactive oxygen species was enhanced, and mitochondrial membrane potential, mtDNA copy number and cellular oxygen consumption rate were remarkably decreased compared with wild type cybrid cells. The homoplasmic 10003T>C mutation in the mitochondrial tRNA(Gly) gene suggested to be as a pathogenesis-related mutation which might contribute to the maternal inherited diabetes in the Han Chinese family. PMID- 26134046 TI - Alcohol consumption and liver cancer risk: a meta-analysis. AB - PURPOSE: Alcohol is a confirmed risk factor of liver cancer. Yet, its dose response function and synergistic effects with other risk factors remain unclear. METHODS: We performed a meta-analysis on publications up to May 2014. A total of 112 publications were identified. The meta-relative risk (mRR) and the dose response trend were calculated. Tests for heterogeneity, publication bias, and sensitivity analyses were performed. The synergy index (SI) was recorded or calculated, whenever possible. RESULTS: Compared to individuals who never drank or drank at very low frequencies, the mRR for ever drinkers was 1.29 (95% confidence interval, CI 1.16-1.42) and 1.46 (95% CI 1.27-1.65) for case-control studies, and 1.07 (95% CI 0.87-1.27) for cohort studies. Being a current drinker was associated with an increased liver cancer risk in case-control studies (mRR = 1.55, 95% CI 0.38-2.73), but not in cohort studies (mRR = 0.86, 95% CI 0.74 0.97). The dose-response relation between alcohol and liver cancer was apparent with RR = 1.08 (95% CI 1.04-1.11) for 12 g/day (~1 drink), 1.54 (95% CI 1.36 1.74) for 50 g/day, 2.14 (95% CI 1.74-2.62) for 75 g/day, 3.21 (95% CI 2.34-4.40) for 100 g/day, and 5.20 (95% CI 3.25-8.29) for 125 g/day of alcohol consumption. There were synergistic effects of alcohol consumption with hepatitis (S = 2.14, 95% CI 1.31-2.98) and with diabetes (S = 3.57, 95% CI 2.29-4.84) on the risk of liver cancer, although this may be subject to publication bias. CONCLUSION: Overall, one alcoholic drink per day (~12 g/day) may be associated with a 1.1 times higher liver cancer risk. Further studies on the synergistic effects of alcohol consumption and other major risk factors are warranted. PMID- 26134045 TI - Prognostic Value of Biomarkers in Acute Non-massive Pulmonary Embolism: A Systematic Review and Meta-analysis. AB - BACKGROUND: Various biomarkers have been evaluated to risk stratify patients with acute pulmonary embolism (PE). We aimed to summarize the available evidence to compare the prognostic value of three most widely studied biomarkers in normotensive patients with acute PE. METHOD: A systematic literature review of database, including Pubmed, EMBASE and Cochrane, was done. Studies were included if those were done on patients with acute PE and serum troponin or brain natriuretic peptide and N-terminal proBNP (BNP/NT-proBNP) or Heart-type fatty acid-binding protein (H-FABP) assay was done. The primary end point was short term all-cause mortality. The secondary end points were PE-related mortality and serious adverse events. RESULTS: All three biomarkers were significantly associated with increased risk for short-term all-cause mortality, PE-related mortality and serious adverse events. All-cause mortality: troponin [odds ratio (OR) 4.80; 95% CI 3.25-7.08, I(2) = 54%], BNP or NT-proBNP (OR 7.98; 95% CI 4.34 14.67, I(2) = 0%); PE-related mortality: troponin (OR 3.80; 95% CI 2.74-5.27, I(2) = 0%), BNP or NT-proBNP (OR 7.57; 95% CI 2.89-19.81, I (2) = 0%) and H-FABP (OR 25.97; 95% CI 6.63-101.66, I(2) = 40%). H-FABP has the lowest negative likelihood ratio (NLR) of 0.17 for mortality followed by high-sensitive cardiac troponin T (hs-cTnT) with NLR of 0.21. CONCLUSION: None of the biomarker identifies a subgroup of patients who can be managed as an outpatient versus patients who may get benefit from thrombolytics with certainty; however, H-FABP and hs-cTnT showed some promising results and should be investigated further. PMID- 26134047 TI - Home paint exposures and risk of childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium. AB - PURPOSE: It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression. RESULTS: Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting. CONCLUSIONS: Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods. PMID- 26134048 TI - The negative impact of tobacco smoking on survival after prostate cancer diagnosis. AB - PURPOSE: Tobacco smoking has been found to increase prostate cancer (PCa) mortality in cohorts of healthy men, but its effects on prognosis of men with PCa are still unclear. This study investigated the role of smoking on long-term survival after PCa diagnosis. METHODS: A retrospective cohort including 780 men with incident PCa previously enrolled (between 1995 and 2002) as cases in an Italian case-control study. Information on vital status up to 2013 (median follow up 13 years) and cause of death were retrieved through health archives. Hazard ratios (HRs) of all-cause and PCa-specific death, and corresponding 95 % confidence intervals (CIs), were calculated using Cox models, adjusting for Gleason score and major confounders. RESULTS: Out of 263 PCa deceased patients, 81 died because of PCa. Smokers at PCa diagnosis reported increased risks of all cause (HR = 1.5, 95% CI 1.1-2.2) and PCa death (HR = 2.0, 95% CI 1.0-3.8), as compared to never smokers. Dose-response effects emerged according to smoking intensity (HRs for >15 cigarettes/day: 1.9, 95% CI 1.3-3.0, for all causes and 2.3, 95% CI 1.1-4.9, for PCa) and duration (HRs for >45 years: 1.7, 95% CI 1.1 2.6, for all causes and 2.6, 95% CI 1.2-5.5, for PCa). Conversely, former smokers at PCa diagnosis showed no statistically significant higher risks of PCa death. The effects of smoking were consistent in strata of Gleason score. CONCLUSIONS: Current smoking at PCa diagnosis negatively impacted PCa-specific, long-term survival, regardless of Gleason score. Our findings suggest that smoking could be a modifiable risk factor to improve prognosis of men diagnosed with PCa. PMID- 26134049 TI - Revving up the immune therapy business. AB - Giant pharmaceutical companies and biotech startups are seizing opportunities to advance their oncologic immunotherapy business and provide patients with more effective treatment options. PMID- 26134050 TI - Biomarkers define distinct types of diffuse glioma. AB - Three genetic markers performed far better than histologic criteria to classify diffuse low-grade gliomas, laying the foundation for molecular diagnosis of this heterogeneous group of brain tumors. PMID- 26134051 TI - Outcomes of emergency department thoracotomy in a tertiary care Canadian trauma centre. AB - OBJECTIVE: Emergency department thoracotomy (EDT) is a rare and potentially life saving intervention performed for trauma patients in extremis. EDT is rare at Canadian trauma centres because of our infrequent occurrence of penetrating trauma. This study was undertaken to evaluate outcomes at a Canadian level 1 trauma facility and compare survival to large published datasets. Also, we evaluated the appropriateness of an EDT performed at our centre based on published national guidelines. METHODS: Retrospective medical record review of all patients undergoing an EDT during their resuscitation in the emergency department. Records were identified using our trauma registry, and all charts were manually reviewed. The primary outcome was survival to hospital discharge. RESULTS: Over a 20-year period, 58 EDTs were performed with 6 (10.3%) survivors. Patients undergoing an EDT secondary to penetrating trauma had the highest survival (5 of 24 patients or 20.8% survival) compared to patients undergoing an EDT for blunt trauma (1 of 34 patients or 2.9% survival). Patients undergoing an EDT who had not suffered cardiac arrest represented the group with the highest survival rate (3 of 6 patients or 50% survival). The majority of EDTs (79.3%) were indicated, and no patient undergoing an EDT survived if it was performed outside of published guidelines. CONCLUSIONS: Survival following an EDT in our small, regional trauma centre is consistent with survival rates from larger published datasets. An EDT should continue to be performed under accepted clinical indications. PMID- 26134052 TI - Predictors of Low-Acuity Emergency Department Use by Patients Enrolled in a Family Health Team. AB - BACKGROUND: The primary aim of this study was to determine the characteristics and develop a predictive model describing low acuity users of the emergency department (ED) by patients followed by a family health team (FHT). The secondary aim was to contrast this information with characteristics of high acuity users. We also sought to determine what factors were predictive of leaving without being seen (LWBS). METHODS: This retrospective descriptive correlational study explored characteristics and factors predictive of low acuity ED utilization. The sample included all FHT patients with ED visits in 2011. The last ED record was chosen for review. Sex, age, Canadian Triage and Acuity Scale (CTAS), presenting complaint(s), time of day, day of week, number of visits, and diagnosis were recorded. RESULTS: Of 1580 patients who visited the ED in 2011, 56% were CTAS 1-3 visits, 24% CTAS 4-5 and 20% had no CTAS recorded. Patients who were older than age 65 were approximately half as likely to have a CTAS level of 4-5 compared to younger patients (OR=0.605, CI=0.441,0.829). Patients older than age 65 were 1.75 times more likely to be CTAS level 1-2 (OR=1.745, CI=1.277, 2.383). Patients who went to the ED during the day were less likely to LWBS compared to night visits (OR=0.697, CI=0.532, 0.912). Interpretation Most low acuity ED utilization is by patients under the age of 65, while high acuity ED utilization is more common among patients older than age 65. Patients are more likely to LWBS during late evening and overnight periods (9 pm-7 am). PMID- 26134053 TI - Outcome Feedback within Emergency Medicine Training Programs: An Opportunity to Apply the Theory of Deliberate Practice? AB - OBJECTIVES: Outcome feedback is the process of learning patient outcomes after their care within the emergency department. We conducted a national survey of Canadian Royal College emergency medicine (EM) residents and program directors to determine the extent to which active outcome feedback and follow-up occurred. We also compared the perceived educational value of outcome feedback between residents and program directors. METHODS: We distributed surveys to all Royal College-accredited adult and pediatric EM training programs using a modified Dillman method. We analyzed the data using student's t-test for continuous variables and Fisher's exact test for categorical variables. RESULTS: We received 210 completed surveys from 260 eligible residents (80.8%) and 21 of 24 program directors (87.5%) (overall 81.3%). Mandatory active outcome feedback was not present in any EM training program for admitted or discharged patients (0/21). Follow-up was performed electively by 89.4% of residents for patients admitted to the hospital, and by 44.2% of residents for patients discharged home. A majority of residents (76.9%) believed that patient follow-up should be mandatory compared to 42.9% of program directors (p=0.002). The perceived educational value of outcome feedback was 5.8/7 for residents and 5.1/7 for program directors (difference 0.7; p=0.002) based on a seven-point Likert scale (1=not important; 7=very important). CONCLUSION: While Canadian EM training programs do not mandate follow-up, it is performed electively by the majority of residents surveyed. Residents place a significantly greater educational value on outcome feedback than their program directors, and believe that follow-up should be a mandatory component of EM residencies. PMID- 26134054 TI - Emergency medicine residents' beliefs about contributing to an online collaborative slideshow. AB - OBJECTIVE: Collaborative writing applications (CWAs), such as the Google DocsTM platform, can improve skill acquisition, knowledge retention, and collaboration in medical education. Using CWAs to support the training of residents offers many advantages, but stimulating them to contribute remains challenging. The purpose of this study was to identify emergency medicine (EM) residents' beliefs about their intention to contribute summaries of landmark articles to a Google DocsTM slideshow while studying for their Royal College of Physicians and Surgeons of Canada (RCPSC) certification exam. METHOD: Using the Theory of Planned Behavior, the authors interviewed graduating RCPSC EM residents about contributing to a slideshow. Residents were asked about behavioral beliefs (advantages/disadvantages), normative beliefs (positive/negative referents), and control beliefs (barriers/facilitators). Two reviewers independently performed qualitative content analysis of interview transcripts to identify salient beliefs in relation to the defined behaviors. RESULTS: Of 150 eligible EM residents, 25 participated. The main reported advantage of contributing to the online slideshow was learning consolidation (n=15); the main reported disadvantage was information overload (n=3). The most frequently reported favorable referents were graduating EM residents writing the certification exam (n=16). Few participants (n=3) perceived any negative referents. The most frequently reported facilitator was peer-reviewed high-quality scientific information (n=9); and the most frequently reported barrier was time constraints (n=22). CONCLUSION: Salient beliefs exist regarding EM residents' intention to contribute content to an online collaborative writing project using a Google DocsTM slideshow. Overall, participants perceived more advantages than disadvantages to contributing and believed that this initiative would receive wide support. However, participants reported several barriers that need to be addressed to increase contributions. Our intention is for the beliefs identified in this study to contribute to the design of a theory-based questionnaire to explore determinants of residents' intentions to contribute to an online collaborative writing project. This will help develop implementation strategies for increasing contributions to other CWAs in medical education. PMID- 26134055 TI - Accuracy of physician-estimated probability of brain injury in children with minor head trauma. AB - OBJECTIVE: To evaluate the accuracy of physician estimates of the probability of intracranial injury in children with minor head trauma. METHODS: This is a subanalysis of a large prospective multicentre cohort study performed from July 2001 to November 2005. During data collection for the derivation of a clinical prediction rule for children with minor head trauma, physicians indicated their estimate of the probability of brain injury visible on computed tomography (P Injury) and the probability of injury requiring intervention (P-Intervention) by choosing one of the following options: 0%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 90%, and 100%. We compared observed frequencies to expected frequencies of injury using Pearson's chi2-test in analyses stratified by the level of each type of predicted probability and by year of age. RESULTS: In 3771 eligible subjects, the mean predicted risk was 4.6% (P-Injury) and 1.4% (P Intervention). The observed frequency of injury was 4.1% (any injury) and 0.6% (intervention). For all levels of P-Injury from 1% to 40%, the observed frequency of injury was consistent with the expected frequency. The observed frequencies for the 50%, 75%, and 90% levels were lower than expected (p<0.05). For estimates of P-Intervention, the observed frequency was consistently higher than the expected frequency. Physicians underestimated risk for infants (mean P Intervention 6.2%, actual risk 12.3%, p<0.001). CONCLUSIONS: Physician estimates of probability of any brain injury in children were collectively accurate for children with low and moderate degrees of predicted risk. Risk was underestimated in infants. PMID- 26134056 TI - A prehospital treat-and-release protocol for supraventricular tachycardia. AB - OBJECTIVE: Paroxysmal supraventricular tachycardia (SVT) is a common dysrhythmia treated in the prehospital setting. Emergency medical service (EMS) agencies typically require patients treated for SVT to be transported to the hospital. This retrospective cohort study evaluated the impact, paramedic adherence, and patient re-presentation rates of a treat-and-release (T+R) protocol for uncomplicated SVT. METHODS: Data were linked from the Alberta Health Services EMS electronic patient care record (EPCR) database for the City of Calgary to the Regional Emergency Department Information System (REDIS). All SVT patients treated by EMS between September 1, 2010, and September 30, 2012, were identified. Databases were queried to identify re-presentations to EMS or an emergency department (ED) within 72 hours of T+R. RESULTS: There were 229 confirmed SVT patient encounters, including 75 T+R events. Of these 75 T+R events, 10 (13%, 95% confidence interval [CI] [7.4, 23]) led to an EMS re presentation within 72 hours, and 4 (5%, 95% CI [2.1, 13]) led to an ED. All re presentations were attributed to a single individual. After excluding 15 records that were incomplete due to limitations in the EPCR platform, 43 of 60 (72%) T+R encounters met all protocol criteria for T+R. CONCLUSION: The T+R protocol evaluated in this study applied to a significant proportion of patients presenting to EMS with SVT. Risk of re-presentation following T+R was low, and paramedic protocol adherence was reasonable. T+R appears to be a viable option for uncomplicated SVT in the prehospital setting. PMID- 26134057 TI - Prolonged prehospital tourniquet placement associated with severe complications: a case report. PMID- 26134058 TI - CAEP 2014 Academic symposium: "How to make research succeed in your department: How to fund your research program". AB - OBJECTIVE: We sought to gather a comprehensive list of funding strategies and opportunities for emergency medicine (EM) centres across Canada, and make recommendations on how to successfully fund all levels of research activity, including research projects, staff salaries, infrastructure, and researcher stipends. METHODS: We formed an expert panel consisting of volunteers recognized nationally for their scholarly work in EM. First, we conducted interviews with academic leaders and researchers to obtain a description of their local funding strategies using a standardized open-ended questionnaire. Panelists then identified emerging funding models. Second, we listed funding opportunities and initiatives at the provincial, national, and international levels. Finally, we used an iterative consensus-based approach to derive pragmatic recommendations after incorporating comments and suggestions from participants at an academic symposium. RESULTS: Our review of funding strategies identified four funding models: 1) investigator dependent model, 2) practice plan, 3) generous benefactor, and 4) mixed funding. Recommendations in this document include approaches for research contributors and producers (seven recommendations), for local academic leaders (five recommendations), and for national organizations, such as the Canadian Association of Emergency Physicians (CAEP) (three recommendations). CONCLUSIONS: Funding for research in EM varies across Canada and is largely insecure. We offer recommendations to help facilitate funding for large and small projects, for salary support, and for local and national leaders to advance EM research. We believe that these recommendations will increase funding for all levels of EM research activity, including research projects, staff salaries, infrastructure, and researcher stipends. PMID- 26134059 TI - Negative Word Production in Adults With Right Hemisphere Brain Damage: Effects of Implicit Assessment and Contextual Bias. AB - PURPOSE: Both theory and evidence suggest that unilateral right hemisphere brain damage (RHD) should impair the processing of negative emotions. Typical metalinguistic assessments, however, may obscure processing strengths. This study investigated whether adults with RHD would produce proportionately fewer negative emotion words than control participants in an implicit assessment task and whether a negatively toned contextual bias would enhance performance. METHODS: Eleven participants with RHD and 10 control participants without brain damage watched a video in 2 parts and described each segment. Between segments, participants evaluated the emotion conveyed by sentences designed to induce the negative bias. RESULTS: The primary outcome measure, percentage of negative emotion words in video descriptions, did not differ between groups. After the contextual bias, this measure significantly increased for both groups, whereas production of motion words, a control variable, remained constant. CONCLUSIONS: Findings are consistent with a view that attributes some deficient RHD performances to the nature and/or demands of explicit metalinguistic assessment tasks. These results call for modulation of prevailing hypotheses that attribute negative emotion processing as an undifferentiated whole solely to the right cerebral hemisphere. The results also further substantiate the rationale of an experimental treatment that exploits contextual bias and priming for individuals with RHD. PMID- 26134060 TI - WITHDRAWN: Diclofenac for acute pain in children. PMID- 26134061 TI - Chemically Modified Graphene: The Influence of Structural Properties on the Assessment of Antioxidant Capacity. AB - Graphene materials obtained by different synthetic routes possess dissimilar amount of defects and surface functionalities, which can influence their electrochemical performance towards the detection of electroactive probes. Oxygen containing groups can be either detrimental to the heterogeneous charge transfer or promote favorable interactions between the graphene surface and the analyte of interest, depending on the structure of the latter. Here, we compared three chemically modified graphenes, obtained by various procedures and carrying different amounts of oxygen functionalities, for the detection of standard gallic acid, a compound commonly used as an index of the antioxidant capacity of food and beverages. We found that electrochemically reduced graphene provided the best electrochemical performance in terms of calibration sensitivity, selectivity, and linearity of response. Our findings are important in order to understand the suitability of graphene platforms for the assessment of food quality. PMID- 26134062 TI - [The intradermal tuberculin test: literature, directive and implementation in practice]. AB - OBJECTIVE: Because of an increase in the number of cases of bovine tuberculosis in southern Germany (Allgau region, mainly in the administrative district Swabia) during recent years, blanket tuberculosis testing was resumed in this region. The aim of this study was to review the veterinarians' current knowledge regarding the technique of the intradermal tuberculin test. As a consequence, a guide with precise instructions for the execution and interpretation of intradermal tuberculin testing in cattle based on the current legislation should be created. MATERIAL AND METHODS: Using a questionnaire, farm-animal practitioners' knowledge and experiences of intradermal tuberculin testing were surveyed, collected and evaluated. Legislative texts on tuberculosis (particularly testing of tuberculosis) were evaluated in their current and previous versions, and compared with the experiences reported by the veterinarians. RESULTS: A total of 137 veterinarians participated and 130 returned questionnaires could be evaluated. Forty-four of the 130 participants were involved in tuberculosis testing when the survey was performed. Of these 44 questionnaires, 42 were incorporated in the final evaluation. The majority of the veterinarians perform the intradermal tuberculosis test as laid down in the Commission Regulation (EC) no. 1226/2002 of 8 July 2002 amending Annex B to Council Directive 64/432/EEC. However, many practitioners do not comply with the requirements of the Commission Regulation (EC) no. 1226/2002 when evaluating the results of the intradermal tuberculosis test. Veterinarians showing the least accordance with required standards only test single animals or work in areas other than Swabia. CONCLUSIONS: In areas severely affected by tuberculosis, the technique of intradermal tuberculosis testing is performed almost as demanded by the Commission Regulation (EC) no. 1226/2002. However, a more uniform and careful approach should be sought when monitoring the results. The guide designed in the context of this study can help to improve the performance of the intradermal tuberculosis test. The information from the literature review also shows that there is currently no standardized method of intradermal tuberculosis testing. PMID- 26134063 TI - An ultralow background substrate for protein microarray technology. AB - We herein report an ultralow background substrate for protein microarrays. Conventional protein microarray substrates often suffer from non-specific protein adsorption and inhomogeneous spot morphology. Consequently, surface treatment and a suitable printing solution are required to improve the microarray performance. In the current work, we improved the situation by developing a new microarray substrate based on a fluorinated ethylene propylene (FEP) membrane. A polydopamine microspot array was fabricated on the FEP membrane, with proteins conjugated to the FEP surface through polydopamine. Uniform microspots were obtained on FEP without the application of a special printing solution. The modified FEP membrane demonstrated ultralow background signal and was applied in protein and peptide microarray analysis. PMID- 26134064 TI - Ameliorative effects of Nigella sativa on dyslipidemia. AB - INTRODUCTION: Dyslipidemia is an established risk factor for ischemic heart disease. Nigella sativa (NS) is a medicinal plant that has been used for the treatment and prevention of a variety of diseases, in particular hyperlipidemia. METHODS: We reviewed the existing literature published until 2014 by using the following keywords: ''Nigella sativa'', ''black cumin'', ''black seeds'', ''thymoquinone'', and ''lipid''. RESULTS: In the conducted studies, different preparations of NS including seed powder (100 mg-20 g daily), seed oil (20-800 mg daily), thymoquinone (3.5-20 mg daily), and seed extract (methanolic extract especially), were shown to reduce plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, but the effect on high-density lipoprotein cholesterol (HDL-C) was not significant. NS and thymoquinone have been reported to be safe and well tolerated with no severe adverse effect. In clinical trials, NS was found to be effective when added as adjunct to standard antihyperlipidemic and antidiabetic medications. Lipid-modifying effects of NS could be attributed to the inhibition of intestinal cholesterol absorption, decreased hepatic cholesterol synthesis, and up-regulation of LDL receptors. CONCLUSIONS: Overall, the evidence from experimental and a clinical studies suggests that NS seeds are a promising natural therapy for dyslipidemic patients. PMID- 26134066 TI - ENDOCRINOLOGY AND ART. Proportionate dwarfism in a painting of Rodrigo de Villandrando (1620). PMID- 26134065 TI - Tadalafil modulates aromatase activity and androgen receptor expression in a human osteoblastic cell in vitro model. AB - PURPOSE: Phosphodiesterase type-5 inhibitor (PDE5i) tadalafil administration in men with erectile dysfunction is associated with increased testosterone/estradiol ratio, leading to hypothesize a potential increased effect of androgen action on target tissues. We aimed to characterize, in a cellular model system in vitro, the potential modulation of aromatase and sex steroid hormone receptors upon exposure to tadalafil (TAD). METHODS: Human osteoblast-like cells SAOS-2 were chosen as an in vitro model system since osteoblasts are target of steroid hormones. Cells were tested for viability upon TAD exposure, which increased cell proliferation. Then, cells were treated with/without TAD for several times to evaluate potential modulation in PDE5, aromatase (ARO), androgen (AR) and estrogen (ER) receptor expression. RESULTS: Osteoblasts express significant levels of both PDE5 mRNA and protein. Exposure of cells to increasing concentrations of TAD (10(-8)-10(-7) M) decreased PDE5 mRNA and protein expression. Also, TAD inhibited ARO mRNA and protein expression leading to an increase in testosterone levels in the supernatants. Interestingly, TAD increased total AR mRNA and protein expression and decreased ERalpha, with an increased ratio of AR/ER, suggesting preferential androgenic vs estrogenic pathway activation. CONCLUSIONS: Our results demonstrate for the first time that TAD decreases ARO expression and increases AR protein expression in human SAOS-2, strongly suggesting a new control of steroid hormones pathway by PDE5i. These findings might represent the first evidence of translational actions of PDE5i on AR, which leads to hypothesize a growing relevance of this molecule in men with prostate cancer long-term treated with TAD for sexual rehabilitation. PMID- 26134067 TI - Professional knowledge among Swedish and Saudi healthcare practitioners regarding oro-facial pain in children and adolescents. AB - Oro-facial pain (OFP) and temporomandibular disorders (TMD) in children and adolescents are a growing problem. To meet patients' healthcare needs, professionals must perform their work intuitively and with quality. Therefore, a high degree of professional knowledge is necessary. To investigate the professional knowledge regarding OFP/TMD in children and adolescents among Swedish and Saudi Arabian dental and medical specialists compared with Swedish OFP specialists. One questionnaire including the four domains Chronic pain and behaviour; Aetiology; Diagnosis and classification; Treatment and prognosis was distributed to 383 potential participants, that is physicians and dentists in Sweden and Saudi Arabia. The Swedish OFP/TMD specialists were used as a reference group. The response rates from Sweden and Saudi Arabia were 49% and 86%, respectively. The degree of agreement was highest in the domain Chronic pain and behaviour, especially for the Swedish groups. Regarding the other three domains, the agreement was modest to poor. In general, Swedish groups showed a higher agreement with Swedish OFP/TMD specialists than Saudi Arabian groups. This study shows that professional knowledge regarding OFP/TMD in children and adolescents is limited among Swedish and Saudi Arabian dental and medical professionals compared to Swedish OFP/TMD specialists. In Swedish groups, the professional knowledge is more accurate than in the corresponding Saudi Arabian. With these results in mind, and the frequent prevalence of OFP/TMD in children and adolescents, one can draw the conclusion that there is a need for modern medical education regarding OFP/TMD among both physicians and dentists, especially in Saudi Arabia. PMID- 26134068 TI - Comparative Study on Therapeutic Efficacy Between Hand-Assisted Laparoscopic Surgery and Conventional Laparotomy for Acute Obstructive Right-Sided Colon Cancer. AB - INTRODUCTION: This retrospective study aims to compare open colectomy and hand assisted laparoscopic surgery (HALS) in the management of acute obstructive right sided colon cancer and to analyze and evaluate the feasibility and safety of HALS. PATIENTS AND METHODS: Ten consecutive patients who underwent hand-assisted laparoscopic right hemicolectomy due to acute obstructive right-sided colon cancer were retrospectively well matched with 25 patients scheduled for a conventional laparotomy during the same time. Demographic, intraoperative, and postoperative data were assessed. RESULTS: The HALS group had the advantage in the length of incision (5.8+/-0.7 cm) over the conventional group (16+/-2.3 cm) (P<.05), and the mean blood loss during the operations was significantly less in the HALS group (30+/-15.2 mL) than in the laparotomy group (90+/-29.4 mL) (P<.05). Moreover, the time of postoperative ambulation was earlier (2.5+/-0.8 days versus 3.2+/-0.9 days) (P<.05). Seven cases underwent intestinal decompression for severe intestinal dilatation and had a satisfactory result. The hand-assisted device can fairly meet the demands of a minimally invasive operation and can protect the abdominal incision and avoid infection. There was no intergroup difference in complication rate, although the conventional group had a higher rate. CONCLUSIONS: In this study, compared with conventional laparotomy for acute obstructive right-sided colon neoplasm, HALS is associated with less blood loss, shorter incision, and earlier ambulation. Emergency laparoscopic-assisted right hemicolectomy can be safely performed in patients with obstructing right-sided colonic carcinoma. If practiced more, it might be advocated as a bridge between the conventional open approach and traditional laparoscopic surgery. PMID- 26134069 TI - First Report: Robot-Assisted Total Pelvic Exenteration for Locally Advanced Prostate Cancer. AB - Pelvic exenteration is used in the treatment of several pelvic cancers, including those of the rectum, uterus, and bladder. We report the first case of robotic pelvic exenteration for the treatment of symptomatic prostate cancer involving the rectum and bladder. A six-port transperitoneal robotic approach was used. Bilateral extended lymphadenectomy up to the inferior mesenteric artery was performed. The rectum and bladder were removed en bloc, and a double-barrel anastomosis was then performed with both ureters being connected to the lower opening of the colostomy. Operative time was 249 minutes, and estimated blood loss was 600 mL. No intraoperative or postoperative complications were recorded. Biopsy of the rectum and bladder showed prostatic adenocarcinoma with a Gleason score of 9 (5+4), and 1 of 17 nodes was positive for cancer. Postoperative prostate-specific antigen level was 1.24 ng/mL. The patient is already 19 months after surgery with optimal quality of life. Thus pelvic exenteration is a feasible alternative for highly symptomatic prostate cancer involving adjacent pelvic organs. PMID- 26134070 TI - Duodenotubular Flap-New Biliary Reconstructive Procedure. AB - BACKGROUND: Although Roux-en-Y hepaticojejunostomy is considered the gold standard of biliary reconstruction after excision of a choledochal cyst, there is increasing popularity of hepaticoduodenostomy, as it is easier to perform laparoscopically and provides physiologic bile drainage into the duodenum. Our animal research study had the goal to develop and test a new biliary reconstructive procedure (the duodenotubular flap [DTF]), with the advantages of providing physiological bile flow into the duodenum, technical simplicity of duodenal conduit construction, and ability of endoscopic assessment in case of complications. MATERIALS AND METHODS: The DTF procedure consists of transection of the common bile duct (CBD), construction of the DTF from the second part of the duodenum, and biliary-enteric anastomosis. The first group of 6 dogs underwent reconstruction as a single surgical procedure. The second group of 4 dogs underwent the DTF procedure after the preparatory step of laparoscopic clipping of the CBD (for 7 days), to simulate the pathology of the choledochal cyst (extrahepatic biliary obstruction) and to ease the anastomosis. Laboratory analyses were performed pre- and postoperatively. RESULTS: From the first group, 3 dogs developed a postoperative leak at the biliary-enteric anatomosis. The leak was recognized on postoperative day 4 in 2 dogs. They underwent an emergency abdominal exploration with redo anastomosis and had a complete recovery. The third dog died suddenly on postoperative day 10. Autopsy revealed incomplete disruption of the biliary-enteric anastomosis. In the second group, 3 dogs had an uneventful recovery, but 1 died on postoperative day 3. Autopsy revealed intraperitoneal bleeding with intact anastomotic and staple sites. None of the dogs in either group experienced leak at the staple lines, and none of the 8 surviving dogs developed postoperative cholangitis during the follow-up period from 15 to 20 months. CONCLUSIONS: The DTF procedure is feasible, simple, and quick, simulating physiological anatomy. Regarding the safety, a wide anastomosis seems to be the core of success. PMID- 26134071 TI - Multicomponent mannose-containing liposomes efficiently deliver RNA in murine immature dendritic cells and provide productive anti-tumour response in murine melanoma model. AB - Here we demonstrate the ability of mannosylated liposomes (ML) targeted to mannose receptors (MR) to perform the targeted delivery of model plasmid DNA encoding EGFP and total tumour RNA into murine bone-marrow-derived dendritic cells (DCs) and enhance the efficiency of anti-tumour response triggered by these DCs in murine melanoma model. ML consist of cationic lipid 2X3 (1,26-Bis(cholest 5-en-3beta-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride), helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), and 2.5, 5 or 10% mol. of novel mannosylated lipoconjugates. In the structure of lipoconjugates D-mannose was attached to ditetradecylglycerol residue via succinyl (lipoconjugate 1) or diethylsquarate (lipoconjugate 2) linker groups. ML spontaneously form complexes with plasmid DNA and RNA due to electrostatic interaction between positively charged lipid amino group and negatively charged phosphate of nucleic acids. ML demonstrated the benefit in transfection efficiency (TE) of pDNA into DC progenitors and immature DCs in comparison with the control liposomes at low N/P (nitrogen to phosphate) ratios (1/1 and 2/1) but not at high N/P ratios where the TE was comparable with control liposomes. Moreover, ML at low N/P were more effective in RNA delivery into immature DCs in comparison with DC progenitors. At high N/P ratios liposomal formulations containing 5 and 10% mol. of mannosylated lipoconjugate 2 with diethylsquarate linker were the most effective (up to 50% of transfected cells). DCs transfected ex vivo with ML/melanoma B16 RNA complexes after i.v. injection into mice caused five- to six-fold inhibition of melanoma lung metastasis number. Moreover, the i.v. injection of ML/melanoma B16 RNA complexes into mice induced generation of the melanoma B16-specific cytotoxic T-lymphocytes, which were two-fold more efficient in B16 cell killing than those from control liposome group. PMID- 26134072 TI - Assessing potential peptide targeting ligands by quantification of cellular adhesion of model nanoparticles under flow conditions. AB - Sophisticated drug delivery systems are coated with targeting ligands to improve the specific adhesion to surface receptors on diseased cells. In our study, we developed a method with which we assessed the potential of peptide ligands to specifically bind to receptor overexpressing target cells. Therefore, a microfluidic setup was used where the cellular adhesion of nanoparticles with ligand and of control nanoparticles was observed in parallel under the same experimental conditions. The effect of the ligand on cellular binding was quantified by counting the number of adhered nanoparticles with ligand and differently labeled control nanoparticles on single cells after incubation under flow conditions. To provide easy-to-synthesize, stable and reproducible nanoparticles which mimic the surface characteristics of drug delivery systems and meet the requirements for quantitative analysis, latex beads based on amine modified polystyrene were used as model nanoparticles. Two short peptides were tested to serve as targeting ligand on the beads by increasing the specific binding to HuH7 cells. The c-Met binding peptide cMBP2 was used for hepatocyte growth factor receptor (c-Met) targeting and the peptide B6 for transferrin receptor (TfR) targeting. The impact of the targeting peptide on binding was investigated by comparing the beads with ligand to different internal control beads: 1) without ligand and tailored surface charge (electrostatic control) and 2) with scrambled peptide and similar surface charge, but a different amino acid sequence (specificity control). Our results demonstrate that the method is very useful to select suitable targeting ligands for specific nanoparticle binding to receptor overexpressing tumor cells. We show that the cMBP2 ligand specifically enhances nanoparticle adhesion to target cells, whereas the B6 peptide mediates binding to tumor cells mainly by nonspecific interactions. All together, we suggest that cMBP2 is a suitable choice for specific receptor targeting whereas the peptide B6 should not be considered as specific targeting moiety. PMID- 26134073 TI - Robot-assisted cardiac surgery. AB - Recognition of the significant advantages of minimizing surgical trauma has resulted in the development of minimally invasive surgical procedures. Endoscopic surgery offers patients the benefits of minimally invasive surgery, and surgical robots have enhanced the ability and precision of surgeons. Consequently, technological advances have facilitated totally endoscopic robotic cardiac surgery, which has allowed surgeons to operate endoscopically rather than through a median sternotomy during cardiac surgery. Thus, repairs for structural heart conditions, including mitral valve plasty, atrial septal defect closure, multivessel minimally invasive direct coronary artery bypass grafting (MIDCAB), and totally endoscopic coronary artery bypass graft surgery (CABG), can be totally endoscopic. Robot-assisted cardiac surgery as minimally invasive cardiac surgery is reviewed. PMID- 26134074 TI - Chemical Insight into the Adsorption of Chromium(III) on Iron Oxide/Mesoporous Silica Nanocomposites. AB - Magnetic iron oxide/mesoporous silica nanocomposites consisting of iron oxide nanoparticles embedded within mesoporous silica (MCM-41) and modified with aminopropyl functional groups were prepared for application to Cr(III) adsorption followed by magnetic recovery of the nanocomposite materials from aqueous solution. The composite materials were extensively characterized using physicochemical techniques, such as powder X-ray diffraction, thermogravimetric and elemental analysis, nitrogen adsorption, and zeta potential measurements. For aqueous Cr(III) at pH 5.4, the iron oxide/mesoporous silica nanocomposite exhibited a superior equilibrium adsorption capacity of 0.71 mmol/g, relative to 0.17 mmol/g for unmodified mesoporous silica. The aminopropyl-functionalized iron oxide/mesoporous silica nanocomposites displayed an equilibrium adsorption capacity of 2.08 mmol/g, the highest adsorption capacity for Cr(III) of all the materials evaluated in this study. Energy-dispersive spectroscopy (EDS) with transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) experiments provided insight into the chemical nature of the adsorbed chromium species. PMID- 26134075 TI - Effect of Total Dissolved Solids on Fertilization and Development of Two Salmonid Species. AB - Some studies have shown that the early life stages of salmonids are particularly sensitive to elevated concentrations of total dissolved solids (TDS). We evaluated the effect of TDS released in treated effluent into Snap Lake (Northwest Territories, Canada) by the Snap Lake Diamond Mine on two salmonids native to Snap Lake: Salvenius namaycush (lake trout) and Thymallus arcticus (Arctic grayling). Exposures encompassed the embryo-alevin-fry early life stages and extended to 142 days for lake trout and 69 days for Arctic grayling. Such extended testing is uncommon with these two species. Two exposures were conducted with each species, one initiated prior to fertilization, and the other subsequent to fertilization. Fertilization, survival, and growth were not adversely affected for either species by TDS at concentrations >1400 mg/L, with the exception of survival of lake trout, which produced an LC20 of 991 mg/L in one test, and >1484 mg/L in the second test. For the specific TDS composition tested, which was dominated by chloride (45 %-47 %) and calcium (20 %-21 %), the early life stages of these two fish species were relatively insensitive. Although some authors have suggested lower TDS regulatory limits for salmonid early life stages, our study indicates that this is not necessary, at least for these two fish species and for the specific ionic composition tested. PMID- 26134076 TI - Effect of Zinc Supplementation on Serological Response to Vaccination Against Streptococcus Pneumoniae in Patients Undergoing Chemotherapy for Colorectal Cancer. AB - The aim of the study was to evaluate the effect of zinc supplementation on the antibody titer and the 23-valent pneumococcal seroconversion after vaccination in patients undergoing chemotherapy for colorectal cancer. The study included 25 patients undergoing postsurgery chemotherapy for colorectal adenocarcinoma (chemo group). Subjects were assessed in the perioperative period (prevaccination), before chemotherapy (4th wk) and after 3 cycles of chemotherapy (16th wk). Thirty two healthy volunteers (control group) were included in the study. Participants received the 23-valent pneumococcal conjugate vaccine, and capsules containing zinc (Zn) sulfate (70 mg daily) or identical placebo capsules (containing wheat starch with no added Zn) for 16 wk and were randomly allocated on one of the following groups: chemo-Zn (n = 10), chemo-placebo (n = 15), control-Zn (n = 21), and control-placebo (n = 11). The antipneumococcal antibody titer against 6 polysaccharides was analyzed by ELISA and compared using linear mixed models. The seroconversion rate was compared using Fisher's exact test. An immune response to the vaccination against pneumococcus was observed in all participants. In the 16th wk, the polysaccharide 6 concentration was lower in the chemo-Zn group [2.96 (1.74-5.03) MUg/mL] compared with the Chemo-Placebo group [10.75 (5.37-21.54) MUg/mL] and the seroconversion rate was lower in the chemo-placebo (36%) compared with the control-placebo (85%) (P = 0.027). Zinc supplementation did not change the antibody titer after vaccination. However, the lower seroconversion rate observed in the chemo-placebo suggests an influence of zinc in the vaccinal protection. PMID- 26134077 TI - Erratum to: ATP-association to intrabacterial nanotransportation system in Vibrio cholerae. PMID- 26134078 TI - Low Vitamin D Levels are Associated With Need for Surgical Correction of Pediatric Fractures. AB - BACKGROUND: There is growing concern over the relationship between the severity of pediatric fractures and low vitamin D [25-hydroxyvitaminD (25(OH)D)] status. OBJECTIVE: Compare 25(OH)D levels and lifestyle of children with fractures to nonfracture controls to determine if 25(OH)D levels are associated with fractures and if there is a 25(OH)D fragility fracture threshold. METHODS: Pediatric fracture and nonfracture controls were included. Bone health survey and medical record data were analyzed. Fractures were categorized using the Abbreviated Injury Scale (AIS). AIS 3 fractures were identified as fractures that required surgical intervention. Univariate and multivariable ordinal regression analyses were performed to identify potential risk factors for increased fracture severity. RESULTS: A total of 369 fracture patients and 662 nonfracture controls aged 18 years and younger were included. Both groups' 25(OH)D levels were comparable. 25(OH)D was 27.5+/-8.9 in the fracture group compared with 27.4+/-9.1 ng/mL in nonfracture controls (P=0.914). AIS 3 fractures had lower 25(OH)D levels (24.6+/-9.3 ng/mL) versus AIS 1 and 2 (30.0+/-10.8 and 28.3+/-8.4, respectively, P=0.001). Univariate correlations for AIS severity were found with age (P=0.015) and outdoor playtime (P=0.042). Adjusted odds ratios for 25(OH)D levels <12 ng/mL was 55.4 (P=0.037), 25(OH)D between 12 and 20 ng/mL was 6.7 (P=0.039), 25(OH)D between 20 and 30 ng/mL was 2.8 (P=0.208), and 25(OH)D between 30 and 40 was 1.7 (P=0.518). CLINICAL RELEVANCE: Occurrence of a pediatric fracture was not associated with 25(OH)D levels in our study. However, children with lower vitamin D levels were found to be at higher risk for more severe fractures. Early evidence suggests that the target serum level for 25(OH)D should be at least 40 ng/mL in patients less than 18 years of age as the relative risk of more severe fractures increased as 25(OH)D levels decreased <40 ng/mL. LEVEL OF EVIDENCE: Level III. PMID- 26134080 TI - Remarkable shape memory effect of a natural biopolymer in aqueous environment. AB - Remarkable water-stimulated shape memory effect was revealed in a natural biopolymer of peacock's tail covert feathers of which the innate shape can almost be fully recovered after severe deformation by a short hydration step. The shape memory effect manifests a good stability of high recovery rate and ratio during cycles of deformation and subsequent recovery. Both strength and energy absorption efficiency of medullary foam can be recovered despite the apparent decrease in the first deformation stroke caused by structural damage. A kinetic model developed from non-equilibrium thermodynamic fluctuation theory was adopted to describe the shape recovery process by considering the viscoelastic relaxation. The effects of hydration on mechanical properties, recovery kinetics, activation process and dynamic mechanical behaviors were also evaluated. Mechanisms were explored based on the lubrication, swelling effect and structural changes of macromolecular chains or segments in terms of their mobility. This study is expected to aid in understanding the responses of natural biological materials to environmental stimuli and to provide useful information for synthetic shape memory materials from the bio-inspiration perspective. PMID- 26134088 TI - From Definitive Endoderm to Gut-a Process of Growth and Maturation. AB - The intestine and colon carries out vital functions, and their lifelong maintenance is of the upmost importance. Research over the past decades has carefully addressed bowel function, how it is maintained and begun to unravel how disorders such as cancer and inflammatory bowel disease form. In contrast, very little is known about the molecular mechanisms that trigger tissue maturation during development. With this review, our aim is to carefully provide a critical appraisal of the literature to give a state-of-the-art view of intestinal development. Starting from definitive endoderm at gastrulation to the emergence of a structure with mature properties, the tissue undergoes complex morphogenetic processes that rely on both biophysical changes and secreted signaling molecules. We will also discuss how new and exciting developments using in vitro models are likely to provide new insights into this process and potential therapeutic strategies for gastrointestinal disorders. PMID- 26134079 TI - Biomaterial bridges enable regeneration and re-entry of corticospinal tract axons into the caudal spinal cord after SCI: Association with recovery of forelimb function. AB - Severed axon tracts fail to exhibit robust or spontaneous regeneration after spinal cord injury (SCI). Regeneration failure reflects a combination of factors, including the growth state of neuronal cell bodies and the regeneration inhibitory environment of the central nervous system. However, while spared circuitry can be retrained, target reinnervation depends on longitudinally directed regeneration of transected axons. This study describes a biodegradable implant using poly(lactide-co-glycolide) (PLG) bridges as a carrier scaffold to support regeneration after injury. In order to detect regeneration of descending neuronal tracts into the bridge, and beyond into intact caudal parenchyma, we developed a mouse cervical implantation model and employed Crym:GFP transgenic mice. Characterization of Crym:GFP mice revealed that descending tracts, including the corticospinal tract, were labeled by green fluorescent protein (GFP), while ascending sensory neurons and fibers were not. Robust co localization between GFP and neurofilament-200 (NF-200) as well as GFP and GAP-43 was observed at both the rostral and caudal bridge/tissue interface. No evidence of similar regeneration was observed in mice that received gelfoam at the lesion site as controls. Minimal co-localization between GFP reporter labeling and macrophage markers was observed. Taken together, these data suggest that axons originating from descending fiber tracts regenerated, entered into the PLG bridge at the rostral margin, continued through the bridge site, and exited to re-enter host tissue at the caudal edge of the intact bridge. Finally, regeneration through implanted bridges was associated with a reduction in ipsilateral forelimb errors on a horizontal ladder task. PMID- 26134089 TI - Methodological approach to determine minor, considerable, and major treatment effects in the early benefit assessment of new drugs. AB - At the beginning of 2011, the early benefit assessment of new drugs was introduced in Germany with the Act on the Reform of the Market for Medicinal Products (AMNOG). The Federal Joint Committee (G-BA) generally commissions the Institute for Quality and Efficiency in Health Care (IQWiG) with this type of assessment, which examines whether a new drug shows an added benefit (a positive patient-relevant treatment effect) over the current standard therapy. IQWiG is required to assess the extent of added benefit on the basis of a dossier submitted by the pharmaceutical company responsible. In this context, IQWiG was faced with the task of developing a transparent and plausible approach for operationalizing how to determine the extent of added benefit. In the case of an added benefit, the law specifies three main extent categories (minor, considerable, major). To restrict value judgements to a minimum in the first stage of the assessment process, an explicit and abstract operationalization was needed. The present paper is limited to the situation of binary data (analysis of 2 * 2 tables), using the relative risk as an effect measure. For the treatment effect to be classified as a minor, considerable, or major added benefit, the methodological approach stipulates that the (two-sided) 95% confidence interval of the effect must exceed a specified distance to the zero effect. In summary, we assume that our approach provides a robust, transparent, and thus predictable foundation to determine minor, considerable, and major treatment effects on binary outcomes in the early benefit assessment of new drugs in Germany. After a decision on the added benefit of a new drug by G-BA, the classification of added benefit is used to inform pricing negotiations between the umbrella organization of statutory health insurance and the pharmaceutical companies. PMID- 26134090 TI - Correction: Enhanced photoelectrochemical water oxidation via atomic layer deposition of TiO2 on fluorine-doped tin oxide nanoparticle films. AB - Correction for 'Enhanced photoelectrochemical water oxidation via atomic layer deposition of TiO2 on fluorine-doped tin oxide nanoparticle films' by Isvar A. Cordova, et al., Nanoscale, 2015, 7, 8584-8592. PMID- 26134091 TI - Is a practice-based rural research network feasible in Europe? AB - Research in family medicine is a well-established entity nationally and internationally, covering all aspects of primary care including remote and isolated practices. However, due to limited capacity and resources in rural family medicine, its potential is not fully exploited yet. An idea to foster European rural primary care research by establishing a practice-based research network has been recently put forward by several members of the European Rural and Isolated Practitioners Association (EURIPA) and the European General Practice Research Network (EGPRN). Two workshops on why, and how to design a practice based research network among rural family practices in Europe were conducted at two international meetings. This paper revisits the definition of practice-based research in family medicine, reflects on the current situation in Europe regarding the research in rural family practice, and discusses a rationale for practice-based research in rural family medicine. A SWOT analysis was used as the main tool to analyse the current situation in Europe regarding the research in rural family practice at both meetings. The key messages gained from these meetings may be employed by the Wonca Working Party on research, the International Federation of Primary Care Research Network and the EGPRN that seek to introduce a practice-based research approach. The cooperation and collaboration between EURIPA and EGPRN creates a fertile ground to discuss further the prospect of a European practice-based rural family medicine research network, and to draw on the joint experience. PMID- 26134092 TI - Explaining fatigue: an examination of patient causal attributions and their (in)congruence with family doctors' initial causal attributions. AB - BACKGROUND: General practitioners (GPs) and patients can have different ideas about the causes of fatigue, which may hinder management of fatigue. OBJECTIVE: To investigate the causal attributions of patients and their GPs for fatigue, their level of agreement, and the association between patients' attributions, and fatigue characteristics and other illness perceptions. METHODS: Baseline data, collected between 2004 and 2006, of a prospective cohort study among 642 adult patients presenting to Dutch primary care practices (n = 147) with a main symptom of fatigue, were used. Patient causal attributions and illness perceptions were measured using the revised illness perception questionnaire (fatigue version). GP causal attributions were measured with an open question included in the form that was completed at the end of the patient's visit. Fatigue severity was measured using the checklist individual strength. RESULTS: Psychosocial causes were among the most often reported causal attributions by both patients and GPs. In 33% of 519 cases, the GP had no idea about the cause whereas the patient did. Overall, the agreement between the first reported causal attribution of patients and GPs was low. Qualitative differences in the labelling of causes were also found. Type of attribution (physical vs psychosocial/psychological) was associated with duration of fatigue (40 vs 25 months), and personal control (score 17.4 vs. 18.9). CONCLUSION: Most patients and GPs had ideas about the causes of fatigue, but differences were found in the first reported causes and the labelling of causes. The findings may provide leads for optimizing communication about fatigue. PMID- 26134093 TI - Plasmonic Vesicles of Amphiphilic Nanocrystals: Optically Active Multifunctional Platform for Cancer Diagnosis and Therapy. AB - Vesicular structures with compartmentalized, water-filled cavities, such as liposomes of natural and synthetic amphiphiles, have tremendous potential applications in nanomedicine. When block copolymers self-assemble, the result is polymersomes with tailored structural properties and built-in releasing mechanisms, controlled by stimuli-responsive polymer building blocks. More recently, chemists are becoming interested in multifunctional hybrid vesicles containing inorganic nanocrystals with unique optical, electronic, and magnetic properties. In this Account, we review our recent progress in assembling amphiphilic plasmonic nanostructures to create a new class of multifunctional hybrid vesicles and applying them towards cancer diagnosis and therapy. Localized surface plasmon resonance (LSPR) gives plasmonic nanomaterials a unique set of optical properties that are potentially useful for both biosensing and nanomedicine. For instance, the strong light scattering at their LSPR wavelength opens up the applications of plasmonic nanostructures in single particle plasmonic imaging. Their superior photothermal conversion properties, on the other hand, make them excellent transducers for photothermal ablation and contrast agents for photoacoustic imaging. Of particular note for ultrasensitive detection is that the confined electromagnetic field resulting from excitation of LSPR can give rise to highly efficient surface enhanced Raman scattering (SERS) for molecules in close proximity. We have explored several ways to combine well defined plasmonic nanocrystals with amphiphilic polymer brushes of diverse chemical functionalities. In multiple systems, we have shown that the polymer grafts impart amphiphilicity-driven self-assembly to the hybrid nanoparticles. This has allowed us to synthesize well-defined vesicles in which we have embedded plasmonic nanocrystals in the shell of collapsed hydrophobic polymers. The hydrophilic brushes extend into external and interior aqueous environment to stabilize the vesicular structure. More importantly, we have demonstrated that strong interparticle coupling greatly enhances the optical properties (scattering, photothermal conversion, and SERS) in plasmonic vesicles. In combination with the loading capacity of the vesicles, this technology can provide unique opportunities for integrated diagnosis and therapy, multimodality combination therapy, and imaging-guided therapy. One key property differentiating the plasmonic vesicles from other vesicular structures containing nanocrystals is that we can tailor the interparticle coupling and disintegration of the plasmonic vesicles by altering structural parameters and conformational changes of the covalently bound polymer brushes. This gives us tremendous flexibility to engineer plasmonic vesicles for ultrasensitive detection and targeted therapy. Through bringing together advances in nanochemistry, polymer chemistry, self assembly, and nanophotonics, we expect to further expand our capability of tailoring optical and structural characteristics of plasmonic vesicles to address challenges in medical settings. PMID- 26134094 TI - Age differences in rumination and autobiographical retrieval. AB - OBJECTIVES: Higher well-being in older adults compared to young adults is a well known phenomenon. However, the variables associated with this effect are still uncertain. Negative repetitive thinking (rumination) is a transdiagnostic variable related to psychopathology. It is strongly associated with depression and a lack of specificity in autobiographical retrieval. This research explores age differences in the association of rumination with mood, autobiographical memories and working memory. METHOD: Two groups of participants (older adults versus young adults), recruited through a public announcement, were compared in a cross-sectional study. RESULTS: Older adults ruminated less than young participants. Rumination was positively associated with depression scores but not with working memory scores in both samples. More importantly, the interaction between brooding rumination and negative autobiographical memories was the only significant variable to explain the variance of mood scores in young participants. However, in older participants, the interaction between brooding and positive autobiographical memories significantly explained the variance of mood scores. Digit span forward and the interaction of brooding by negative autobiographical memories also significantly explained mood scores in older adults. CONCLUSION: These results suggest that a different interaction between brooding rumination and the valence of autobiographical memories may be a relevant variable associated with mood differences by age. PMID- 26134096 TI - An Unexpected Cause of Hemoptysis. PMID- 26134095 TI - Occurrence of Ergot and Ergot Alkaloids in Western Canadian Wheat and Other Cereals. AB - A new method was developed to analyze 10 ergot alkaloids in cereal grains. Analytes included both "ine" and "inine" type ergot alkaloids. Validation of the method showed it performed with good accuracy and precision and that minor enhancement due to matrix effects was present during LC-MS/MS analysis, but was mitigated by use of an internal standard. The method was used to survey durum and wheat harvested in 2011, a year in which ergot infection was particularly widespread in western Canada. A strong linear relationship between the concentration of ergot alkaloids and the presence of ergot sclerotia was observed. In addition, shipments of cereals from 2010-2012 were also monitored for ergot alkaloids. Concentrations of total ergot alkaloids in shipments were lower than observed in harvest samples, and averaged from 0.065 mg/kg in barley to 1.14 mg/kg in rye. In shipments, the concentration of ergot alkaloids was significantly lower in wheat of higher grades. PMID- 26134098 TI - Generating patient-specific induced pluripotent stem cells-derived cardiomyocytes for the treatment of cardiac diseases. AB - INTRODUCTION: Induced pluripotent stem cells (iPSC) represent an appealing cell source to develop disease-modeling assays, drug testing assays and cell-based replacement therapies especially for cardiac disorders. AREAS COVERED: The development of efficient protocols to generate pure populations of cardiac myocytes is a prerequisite to provide reproducible, robust and valid assays. Different techniques have been recently proposed that allow production of high yield high-quality cardiomyocytes. In addition, the newly developed genome editing techniques offer multiple opportunities to manipulate the genome of patient-specific iPSC thus generating syngeneic iPSC lines. Genome-editing techniques will also allow engineering of iPSC to make them suitable for replacement therapies. EXPERT OPINION: Since their discovery, iPSCs have shown promise to revolutionize the way human diseases are studied. During the last years, different protocols have been developed to achieve reproducible and efficient differentiation of iPSCs including in cardiac and vascular cells. The recent introduction of the genome-editing techniques now allow targeted manipulation of the genome of patient-specific and control iPSCs lines. This approach would help to address a couple of current limitations, including the generation of isogenic lines for disease modeling and of clinical-grade lines for replacement therapy. PMID- 26134097 TI - Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells. AB - Interferon lambda 4 (IFN-lambda4) is a novel type-III interferon that can be generated only in individuals carrying a DeltaG frame-shift allele of an exonic genetic variant (rs368234815-DeltaG/TT). The rs368234815-DeltaG allele is strongly associated with decreased clearance of hepatitis C virus (HCV) infection. Here, we further explored the biological function of IFN-lambda4 expressed in human hepatic cells-a hepatoma cell line HepG2 and fresh primary human hepatocytes (PHHs). We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Not only did we observe significant intracellular retention of IFN-lambda4 but also detected secreted IFN-lambda4 in the culture media of expressing cells. Secreted IFN-lambda4 induced strong activation of the interferon-stimulated genes (ISGs) in IFN-lambda4-expressing and surrounding cells in transwell assays. Specifically, in PHHs, secreted IFN-lambda4 induced expression of the CXCL10 transcript and a corresponding pro-inflammatory chemokine, IP-10. In IFN-lambda4 expressing HepG2 cells, we also observed decreased proliferation and increased cell death. All IFN-lambda4-induced phenotypes--activation of ISGs, decreased proliferation, and increased cell death--could be inhibited by an anti-IFN lambda4-specific antibody. Our study offers new insights into biology of IFN lambda4 and its possible role in HCV clearance. PMID- 26134099 TI - Magnetic Biocomposites for Remote Melting. AB - A new approach toward the fabrication of biocompatible composites suitable for remote melting is presented. It is shown that magnetite nanoparticles (MNP) can be embedded into a matrix of biocompatible thermoplastic dextran esters. For that purpose, fatty acid esters of dextran with adjustable melting points in the range of 30-140 degrees C were synthesized. Esterification of the polysaccharide by activation of the acid as iminium chlorides guaranteed mild reaction conditions leading to high quality products as confirmed by FTIR- and NMR spectroscopy as well as by gel permeation chromatography (GPC). A method for the preparation of magnetically responsive bionanocomposites was developed consisting of combined dissolution/suspension of the dextran ester and hydrophobized MNPs in an organic solvent followed by homogenization with ultrasonication, casting of the solution, drying and melting of the composite for a defined shaping. This process leads to a uniform distribution of MNPs in nanocomposite as revealed by scanning electron microscope. Samples of different geometries were exposed to high frequency alternating magnetic field. It could be shown that defined remote melting of such biocompatible nanocomposites is possible for the first time. This may lead to a new class of magnetic remote control systems, which are suitable for controlled release applications or self-healing materials. PMID- 26134100 TI - Transcatheter aortic valve implantation: long-term clinical outcome and valve durability. AB - Transcatheter aortic valve implantation (TAVI) is a widely used intervention in patients who are at high risk or contraindicated for cardiac surgery. The procedure is technically feasible in most patients and has very good mid-term clinical outcomes. In this special report, we evaluated the long-term outcome after TAVI and durability of percutaneously implanted aortic valve prostheses by reviewing all available long-term follow-up data. We herein present the clinical and hemodynamic data derived from patients 2-5 years after TAVI and describe all published cases of prosthesis degeneration. PMID- 26134101 TI - Posterior Scleritis: Analysis of Epidemiology, Clinical Factors, and Risk of Recurrence in a Cohort of 114 Patients. AB - PURPOSE: To describe the clinical and epidemiological characteristics of patients with posterior scleritis, and to analyze the response to treatment and time to relapse. METHODS: Retrospective study of 114 cases of posterior scleritis from two tertiary care, university-affiliated, referral centers in the United Kingdom and India between 2004 and 2013. Data included sociodemographic factors, medical history, clinical, laboratory and ultrasound findings, therapies, and outcomes. LogMAR visual acuity at presentation and final visit and time to relapse were the main outcome measures. RESULTS: The mean age was 45.9 +/- 16.8 years, 71.1% were women, and 18 (15.8%) patients had bilateral disease; 71 (62.3%) cases were idiopathic. Rheumatoid polyarthritis (12.28%), systemic lupus erythematous (4.38%) and pANCA(+) systemic vasculitis (5.26%) were the most frequent systemic associations. VA improved by 0.24 +/- 0.36 LogMAR between presentation and last follow up (p < 0.001). The median time to remission was 210 days (95% CI: 184-256 days). Recurrences after remission were observed in 36.63%. The observed incidence rate of posterior scleritis relapse after remission was 15.81% per person-year (95% CI: 11.78-20.77%). Systemic disease was present significantly in patients more than 50 years of age (OR = 2.29; 95% CI: 1.01-5.17; p = 0.044). CONCLUSION: Posterior scleritis is an uncommon disease causing pain and visual loss. In around 40% of the cases, it can be associated with other systemic diseases. Median time to relapse was 210 days. Relapses may occur in around 1 in 3 patients, with an incidence rate of 15.81% per person/year. PMID- 26134102 TI - Diversity Performance Analysis on Multiple HAP Networks. AB - One of the main design challenges in wireless sensor networks (WSNs) is achieving a high-data-rate transmission for individual sensor devices. The high altitude platform (HAP) is an important communication relay platform for WSNs and next generation wireless networks. Multiple-input multiple-output (MIMO) techniques provide the diversity and multiplexing gain, which can improve the network performance effectively. In this paper, a virtual MIMO (V-MIMO) model is proposed by networking multiple HAPs with the concept of multiple assets in view (MAV). In a shadowed Rician fading channel, the diversity performance is investigated. The probability density function (PDF) and cumulative distribution function (CDF) of the received signal-to-noise ratio (SNR) are derived. In addition, the average symbol error rate (ASER) with BPSK and QPSK is given for the V-MIMO model. The system capacity is studied for both perfect channel state information (CSI) and unknown CSI individually. The ergodic capacity with various SNR and Rician factors for different network configurations is also analyzed. The simulation results validate the effectiveness of the performance analysis. It is shown that the performance of the HAPs network in WSNs can be significantly improved by utilizing the MAV to achieve overlapping coverage, with the help of the V-MIMO techniques. PMID- 26134103 TI - Robust and Accurate Modeling Approaches for Migraine Per-Patient Prediction from Ambulatory Data. AB - Migraine is one of the most wide-spread neurological disorders, and its medical treatment represents a high percentage of the costs of health systems. In some patients, characteristic symptoms that precede the headache appear. However, they are nonspecific, and their prediction horizon is unknown and pretty variable; hence, these symptoms are almost useless for prediction, and they are not useful to advance the intake of drugs to be effective and neutralize the pain. To solve this problem, this paper sets up a realistic monitoring scenario where hemodynamic variables from real patients are monitored in ambulatory conditions with a wireless body sensor network (WBSN). The acquired data are used to evaluate the predictive capabilities and robustness against noise and failures in sensors of several modeling approaches. The obtained results encourage the development of per-patient models based on state-space models (N4SID) that are capable of providing average forecast windows of 47 min and a low rate of false positives. PMID- 26134104 TI - On the Design of Smart Parking Networks in the Smart Cities: An Optimal Sensor Placement Model. AB - Smart parking is a typical IoT application that can benefit from advances in sensor, actuator and RFID technologies to provide many services to its users and parking owners of a smart city. This paper considers a smart parking infrastructure where sensors are laid down on the parking spots to detect car presence and RFID readers are embedded into parking gates to identify cars and help in the billing of the smart parking. Both types of devices are endowed with wired and wireless communication capabilities for reporting to a gateway where the situation recognition is performed. The sensor devices are tasked to play one of the three roles: (1) slave sensor nodes located on the parking spot to detect car presence/absence; (2) master nodes located at one of the edges of a parking lot to detect presence and collect the sensor readings from the slave nodes; and (3) repeater sensor nodes, also called "anchor" nodes, located strategically at specific locations in the parking lot to increase the coverage and connectivity of the wireless sensor network. While slave and master nodes are placed based on geographic constraints, the optimal placement of the relay/anchor sensor nodes in smart parking is an important parameter upon which the cost and efficiency of the parking system depends. We formulate the optimal placement of sensors in smart parking as an integer linear programming multi-objective problem optimizing the sensor network engineering efficiency in terms of coverage and lifetime maximization, as well as its economic gain in terms of the number of sensors deployed for a specific coverage and lifetime. We propose an exact solution to the node placement problem using single-step and two-step solutions implemented in the Mosel language based on the Xpress-MPsuite of libraries. Experimental results reveal the relative efficiency of the single-step compared to the two step model on different performance parameters. These results are consolidated by simulation results, which reveal that our solution outperforms a random placement in terms of both energy consumption, delay and throughput achieved by a smart parking network. PMID- 26134105 TI - Highly Sensitive H2S Sensor Based on the Metal-Catalyzed SnO2 Nanocolumns Fabricated by Glancing Angle Deposition. AB - As highly sensitive H2S gas sensors, Au- and Ag-catalyzed SnO2 thin films with morphology-controlled nanostructures were fabricated by using e-beam evaporation in combination with the glancing angle deposition (GAD) technique. After annealing at 500 degrees C for 40 h, the sensors showed a polycrystalline phase with a porous, tilted columnar nanostructure. The gas sensitivities (S = Rgas/Rair) of Au and Ag-catalyzed SnO2 sensors fabricated by the GAD process were 0.009 and 0.015, respectively, under 5 ppm H2S at 300 degrees C, and the 90% response time was approximately 5 s. These sensors showed excellent sensitivities compared with the SnO2 thin film sensors that were deposited normally (glancing angle = 0 degrees , S = 0.48). PMID- 26134106 TI - GPS/GLONASS Combined Precise Point Positioning with Receiver Clock Modeling. AB - Research has demonstrated that receiver clock modeling can reduce the correlation coefficients among the parameters of receiver clock bias, station height and zenith tropospheric delay. This paper introduces the receiver clock modeling to GPS/GLONASS combined precise point positioning (PPP), aiming to better separate the receiver clock bias and station coordinates and therefore improve positioning accuracy. Firstly, the basic mathematic models including the GPS/GLONASS observation equations, stochastic model, and receiver clock model are briefly introduced. Then datasets from several IGS stations equipped with high-stability atomic clocks are used for kinematic PPP tests. To investigate the performance of PPP, including the positioning accuracy and convergence time, a week of (1-7 January 2014) GPS/GLONASS data retrieved from these IGS stations are processed with different schemes. The results indicate that the positioning accuracy as well as convergence time can benefit from the receiver clock modeling. This is particularly pronounced for the vertical component. Statistic RMSs show that the average improvement of three-dimensional positioning accuracy reaches up to 30% 40%. Sometimes, it even reaches over 60% for specific stations. Compared to the GPS-only PPP, solutions of the GPS/GLONASS combined PPP are much better no matter if the receiver clock offsets are modeled or not, indicating that the positioning accuracy and reliability are significantly improved with the additional GLONASS satellites in the case of insufficient number of GPS satellites or poor geometry conditions. In addition to the receiver clock modeling, the impacts of different inter-system timing bias (ISB) models are investigated. For the case of a sufficient number of satellites with fairly good geometry, the PPP performances are not seriously affected by the ISB model due to the low correlation between the ISB and the other parameters. However, the refinement of ISB model weakens the correlation between coordinates and ISB estimates and finally enhance the PPP performance in the case of poor observation conditions. PMID- 26134107 TI - Optical Fiber Sensors for Aircraft Structural Health Monitoring. AB - Aircraft structures require periodic and scheduled inspection and maintenance operations due to their special operating conditions and the principles of design employed to develop them. Therefore, structural health monitoring has a great potential to reduce the costs related to these operations. Optical fiber sensors applied to the monitoring of aircraft structures provide some advantages over traditional sensors. Several practical applications for structures and engines we have been working on are reported in this article. Fiber Bragg gratings have been analyzed in detail, because they have proved to constitute the most promising technology in this field, and two different alternatives for strain measurements are also described. With regard to engine condition evaluation, we present some results obtained with a reflected intensity-modulated optical fiber sensor for tip clearance and tip timing measurements in a turbine assembled in a wind tunnel. PMID- 26134108 TI - UAV-Based Photogrammetry and Integrated Technologies for Architectural Applications--Methodological Strategies for the After-Quake Survey of Vertical Structures in Mantua (Italy). AB - This paper examines the survey of tall buildings in an emergency context like in the case of post-seismic events. The after-earthquake survey has to guarantee time-savings, high precision and security during the operational stages. The main goal is to optimize the application of methodologies based on acquisition and automatic elaborations of photogrammetric data even with the use of Unmanned Aerial Vehicle (UAV) systems in order to provide fast and low cost operations. The suggested methods integrate new technologies with commonly used technologies like TLS and topographic acquisition. The value of the photogrammetric application is demonstrated by a test case, based on the comparison of acquisition, calibration and 3D modeling results in case of use of a laser scanner, metric camera and amateur reflex camera. The test would help us to demonstrate the efficiency of image based methods in the acquisition of complex architecture. The case study is Santa Barbara Bell tower in Mantua. The applied survey solution allows a complete 3D database of the complex architectural structure to be obtained for the extraction of all the information needed for significant intervention. This demonstrates the applicability of the photogrammetry using UAV for the survey of vertical structures, complex buildings and difficult accessible architectural parts, providing high precision results. PMID- 26134109 TI - Tetrathiafulvalene Vinylogue-Fluorene Co-oligomers: Synthesis, Properties, and Supramoleclar Interactions with Carbon Nanotubes. AB - A series of bis(dithiafulvenyl)-end-capped fluorene derivatives was prepared and subjected to a one-pot iodine-promoted oxidative polymerization to yield pi conjugated co-oligomers containing tetrathiafulvalene vinylogue and fluorene repeat units. The resulting pi-oligomers were characterized to take either acyclic or cyclic molecular structures, depending on the pi-conjugation length of the monomer used for the polymerization. Electronic and electrochemical redox properties were examined by UV-vis spectroscopic and cyclic voltammetric analyses, while the supramolecular interactions of the pi-oligomers with single walled carbon nanotubes were investigated by UV-vis-NIR and Raman spectroscopy. PMID- 26134110 TI - Qualitatively Assessing the Experiences of College Students Completing AlcoholEdu: Do Participants Report Altering Behavior After Intervention? AB - To reduce college student drinking and associated alcohol-related consequences, many universities are turning to e-interventions, such as AlcoholEdu. To date, however, results of evaluations examining the impact of AlcoholEdu are mixed. Among these evaluations, few qualitative assessments have examined the experiences and perceptions of students who complete AlcoholEdu. This investigation aimed to assess whether students (a) find the program educational and engaging, (b) implemented specific strategies learned from participation, and (c) self-report altering their behavior as a result of participation. Even though respondents universally reported an increase in alcohol-related knowledge, there was an evident disconnect between this knowledge and their actual behavior. In other words, respondents reported that they did not implement what was taught in AlcoholEdu. Moreover, students highlighted several limitations associated with the program that would have influenced its overall impact, such as ignoring video segments of the program and clicking through assessments simply to complete the task. If used, college administrators and health professionals should implement e interventions such as AlcoholEdu as one component of a multifaceted approach rather than a panacea for the current high-risk drinking practices of college students. PMID- 26134111 TI - Consumer attitudes about the role of multivitamins and other dietary supplements: report of a survey. AB - BACKGROUND: U.S. nutrition surveys find that intakes of many nutrients fall short of recommendations. The majority of U.S. adults use multivitamins and other dietary supplements as one means of improving nutrient intakes. Some policy makers and health professionals appear reluctant to recommend routine use of dietary supplements to fill nutrient gaps in the diet, in part because they are concerned that people will view the supplements as a substitute for dietary improvement and that the use of supplements may lead to overconsumption of micronutrients. Surveys find that in fact users of dietary supplements tend to have better diets and adopt other healthy habits, suggesting that the supplements are viewed as one aspect of an overall effort to improve wellness. Furthermore, evidence demonstrates that the incidence of excess micronutrient intake is low. We report the results of a survey probing consumer attitudes about the role of dietary supplements. METHODS: The Council for Responsible Nutrition funded a survey to measure consumer attitudes about the role of multivitamins, calcium and/or vitamin D supplements, and other supplements in improving dietary intakes. The research was designed and analyzed by FoodMinds and was fielded using Toluna's On-line Omnibus. The weighted sample of 2159 respondents is representative of U.S. adults. RESULTS: Nearly 90% of the survey respondents agreed that multivitamins and supplements of calcium and/or vitamin D can help meet nutrient needs when desirable intakes are not achieved through food alone. At the same time, 80% agreed that dietary supplements should not be used to replace healthy dietary or lifestyle habits, and 82% agreed that people considering taking a high dose, single nutrient supplement should talk with their physician. CONCLUSIONS: These results provide additional support for the conclusion that the vast majority of consumers recognize that multivitamins and other supplements can help fill nutrient gaps but should not be viewed as replacements for a healthy diet. This suggests that policy makers and health professionals could feel comfortable recommending rational dietary supplementation as one means of improving nutrient intakes, without being unduly concerned that such a recommendation would lead consumers to discount the importance of good dietary habits. PMID- 26134112 TI - Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue. AB - INTRODUCTION: The accumulation of neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein, starts spreading early in specific regions in the course of Alzheimer's disease (AD), correlating with the progression of memory dysfunction. The non-invasive imaging of tau could therefore facilitate the early diagnosis of AD, differentiate it from other dementing disorders and allow evaluation of tau immunization therapy outcomes. In this study we characterized the in vitro binding properties of THK5117, a tentative radiotracer for positron emission tomography (PET) imaging of tau brain deposits. RESULTS: Saturation and competition binding studies of (3)H-THK5117 in post-mortem AD brain tissue showed the presence of multiple binding sites. THK5117 binding was significantly higher in hippocampal (p < 0.001) and temporal (p < 0.01) tissue homogenates in AD compared to controls. Autoradiography studies with (3)H-THK5117 was performed on large frozen brain sections from three AD cases who had been followed clinically and earlier undergone in vivo (18)F-FDG PET investigations. The three AD cases showed distinct differences in regional THK5117 binding that were also observed in tau immunohistopathology as well as in clinical presentation. A negative correlation between in vivo (18)F-FDG PET and in vitro (3)H-THK5117 autoradiography was observed in two of the three AD cases. CONCLUSIONS: This study supports that new tau PET tracers will provide further understanding on the role of tau pathology in the diversity of the clinical presentation in AD. PMID- 26134113 TI - Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells. AB - Advanced prostate cancer has highly invasive potential, which may lead to metastasis associated with poor prognosis. Sulforaphane (SFN), abundant in cruciferous vegetables, exhibited effective resistance to carcinogenesis in a variety of tumors. The aim of the present study was to investigate whether SFN inhibited invasion in human prostate cancer cells via sustained activation of ERK1/2 and downstream signaling by an invasion assay, gelatin zymography and western blot analysis. The results showed that SFN inhibited invasion and we characterized the underlying mechanisms in human DU145 prostate cancer cells. SFN (15 uM) changed cell morphology leading to short-cell pseudopodia which may suppress tumor migration and invasion. The Transwell assay showed that SFN phosphorylated ERK1/2 in a dose- and time-dependent manner and significantly inhibited cell invasion, while the effect was reduced by the ERK1/2 blocker PD98059 (25 uM). Furthermore, these effects contributed to the upregulation of E cadherin and the downregulation of CD44v6 and were eradicated by PD98059. Western blot analysis and gelatin zymography showed that SFN decreased the expression and activity of MMP-2. Thus, SFN inhibited invasion by activating ERK1/2 to upregulate E-cadherin and downregulate CD44v6, thereby reducing MMP-2 expression and activity. E-cadherin is an invasion inhibitor, while CD44v6 and MMP-2 are invasion promoters. Therefore, SFN is a prospective therapeutic agent that may be used to prevent invasion in prostate cancer. PMID- 26134114 TI - Serum WFA+ -M2BP levels as a prognostic factor in patients with early hepatocellular carcinoma undergoing curative resection. AB - BACKGROUND & AIMS: Serum tumour markers for hepatocellular carcinoma (HCC) have less prognostic significance in early stage. Serum Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+) -M2BP) levels are reportedly associated with hepatocarcinogenic potential in patients with chronic liver diseases. We investigated the prognostic significance of pretreatment serum WFA(+) -M2BP levels in patients with early-stage HCC. METHODS: A total of 240 patients who underwent hepatic resection for naive Barcelona Clinic Liver Cancer (BCLC) class 0 or A HCC were analysed. WFA(+) -M2BP and tumour markers for HCC were measured from serum obtained just prior to treatment. Post-operative recurrence and survival rates were compared according to these serum markers, tumour stage and Child-Pugh class. RESULTS: There was an association between serum WFA(+) -M2BP levels and the fibrosis grade of resected noncancerous liver tissue, whereas no association was found between WFA(+) -M2BP levels and tumour progression or liver function. In a multivariate analysis, pretreatment serum WFA(+) -M2BP level was associated with recurrence and survival, respectively, independent of HCC progression or fibrosis grade of resected noncancerous liver tissue. Recurrence rates after hepatic resection were significantly higher in patients with a pretreatment serum WFA(+) -M2BP >= 3.00 than those with a pretreatment serum WFA(+) -M2BP < 3.00 (P = 0.0038). Survival rates were lower in patients with a pretreatment serum WFA(+) -M2BP >= 3.00 than those with a pretreatment serum WFA(+) -M2BP < 3.00 (P = 0.0187). CONCLUSIONS: Serum WFA(+) -M2BP level is a prognostic factor for recurrence and survival, in addition to tumour progression and liver function, in patients with early-stage HCC treated with curative hepatic resection. PMID- 26134115 TI - Mothers' perspectives on the perinatal loss of a co-twin: a qualitative study. AB - BACKGROUND: There is a growing body of literature exploring the emotional impact of perinatal loss upon parents but only limited research focussing specifically on the views and experiences of parents who have experienced a loss from a twin or higher order pregnancy. We undertook a qualitative study to provide an in depth understanding of the experiences of mothers who have had a loss from a twin pregnancy and subsequently continued visiting hospital whilst their surviving twin was cared for. METHODS: A qualitative study involving semi-structured interviews. Mothers were recruited from a Neonatal Intensive Care Unit and Fetal Medicine department. Fourteen interviews were carried out with mothers who had experienced a loss in pregnancy or the neonatal period and had a surviving twin on the neonatal unit. Data were analysed using a generative thematic approach. RESULTS: The analysis identified three key themes in the accounts mothers gave of their experiences: the status of 'special'; the importance of trust; and control and empowerment. Where the surviving co-twin remained in hospital for many weeks, mothers described the emotional support of health professionals as crucial to their wellbeing. Few mothers sought formal bereavement support, instead they kept their grief 'on hold' in order to support their surviving baby. Due to the trauma of their loss, mothers reflected that they had been unable to make informed decisions, in particular in relation to the funeral of their deceased baby. CONCLUSIONS: Our study highlighted that there are a specific set of issues for mothers who have lost a baby from a twin pregnancy. Relatively small changes to practice however, made a significant difference to wellbeing during their time in hospital with a surviving twin. Findings from this research will provide insight into the needs of bereaved mothers, will inform healthcare planning and the development of care packages. PMID- 26134116 TI - A conceptual framework: the early and late phases of skeletal muscle dysfunction in the acute respiratory distress syndrome. AB - Patients with acute respiratory distress syndrome (ARDS) often develop severe diaphragmatic and limb skeletal muscle dysfunction. Impaired muscle function in ARDS is associated with increased mortality, increased duration of mechanical ventilation, and functional disability in survivors. In this review, we propose that muscle dysfunction in ARDS can be categorized into an early and a late phase. These early and late phases are based on the timing in relationship to lung injury and the underlying mechanisms. The early phase occurs temporally with the onset of lung injury, is driven by inflammation and disuse, and is marked predominantly by muscle atrophy from increased protein degradation. The ubiquitin proteasome, autophagy, and calpain-caspase pathways have all been implicated in early-phase muscle dysfunction. Late-phase muscle weakness persists in many patients despite resolution of lung injury and cessation of ongoing acute inflammation-driven muscle atrophy. The clinical characteristics and mechanisms underlying late-phase muscle dysfunction do not involve the massive protein degradation and atrophy of the early phase and may reflect a failure of the musculoskeletal system to regain homeostatic balance. Owing to these underlying mechanistic differences, therapeutic interventions for treating muscle dysfunction in ARDS may differ during the early and late phases. Here, we review clinical and translational investigations of muscle dysfunction in ARDS, placing them in the conceptual framework of the early and late phases. We hypothesize that this conceptual model will aid in the design of future mechanistic and clinical investigations of the skeletal muscle system in ARDS and other critical illnesses. PMID- 26134118 TI - The Calcium Goes Meow: Effects of Ions and Glycosylation on Fel d 1, the Major Cat Allergen. AB - The major cat allergen, Fel d 1, is a structurally complex protein with two N glycosylation sites that may be filled by different glycoforms. In addition, the protein contains three putative Ca2+ binding sites. Since the impact of these Fel d 1 structure modifications on the protein dynamics, physiology and pathology are not well established, the present work employed computational biology techniques to tackle these issues. While conformational effects brought upon by glycosylation were identified, potentially involved in cavity volume regulation, our results indicate that only the central Ca2+ ion remains coordinated to Fel d 1 in biological solutions, impairing its proposed role in modulating phospholipase A2 activity. As these results increase our understanding of Fel d 1 structural biology, they may offer new support for understanding its physiological role and impact into cat-promoted allergy. PMID- 26134119 TI - Initial assessment of image quality for low-dose PET: evaluation of lesion detectability. AB - In the context of investigating the potential of low-dose PET imaging for screening applications, we developed methods to assess small lesion detectability as a function of the number of counts in the scan. We present here our methods and preliminary validation using tuberculosis cases. FDG-PET data from seventeen patients presenting diffuse hyper-metabolic lung lesions were selected for the study, to include a wide range of lesion sizes and contrasts. Reduced doses were simulated by randomly discarding events in the PET list mode, and ten realizations at each simulated dose were generated and reconstructed. The data were grouped into 9 categories determined by the number of included true events, from >40 M to <250 k counts. The images reconstructed from the original full statistical set were used to identify lung lesions, and each was, at every simulated dose, quantified by 6 parameters: lesion metabolic volume, lesion-to background contrast, mean lesion tracer uptake, standard deviation of activity measurements (across realizations), lesion signal-to-noise ratio (SNR), and Hotelling observer SNR. Additionally, a lesion-detection task including 550 images was presented to several experienced image readers for qualitative assessment. Human observer performances were ranked using receiver operating characteristic analysis. The observer results were correlated with the lesion image measurements and used to train mathematical observer models. Absolute sensitivities and specificities of the human observers, as well as the area under the ROC curve, showed clustering and performance similarities among images produced from 5 million or greater counts. The results presented here are from a clinically realistic but highly constrained experiment, and more work is needed to validate these findings with a larger patient population. PMID- 26134117 TI - Clinical intervals and diagnostic characteristics in a cohort of prostate cancer patients in Spain: a multicentre observational study. AB - BACKGROUND: Little is known about the healthcare process for patients with prostate cancer, mainly because hospital-based data are not routinely published. The main objective of this study was to determine the clinical characteristics of prostate cancer patients, the, diagnostic process and the factors that might influence intervals from consultation to diagnosis and from diagnosis to treatment. METHODS: We conducted a multicentre, cohort study in seven hospitals in Spain. Patients' characteristics and diagnostic and therapeutic variables were obtained from hospital records and patients' structured interviews from October 2010 to September 2011. We used a multilevel logistic regression model to examine the association between patient care intervals and various variables influencing these intervals (age, BMI, educational level, ECOG, first specialist consultation, tumour stage, PSA, Gleason score, and presence of symptoms) and calculated the odds ratio (OR) and the interquartile range (IQR). To estimate the random inter-hospital variability, we used the median odds ratio (MOR). RESULTS: 470 patients with prostate cancer were included. Mean age was 67.8 (SD: 7.6) years and 75.4% were physically active. Tumour size was classified as T1 in 41.0% and as T2 in 40% of patients, their median Gleason score was 6.0 (IQR:1.0), and 36.1% had low risk cancer according to the D'Amico classification. The median interval between first consultation and diagnosis was 89 days (IQR:123.5) with no statistically significant variability between centres. Presence of symptoms was associated with a significantly longer interval between first consultation and diagnosis than no symptoms (OR:1.93, 95%CI 1.29-2.89). The median time between diagnosis and first treatment (therapeutic interval) was 75.0 days (IQR:78.0) and significant variability between centres was found (MOR:2.16, 95%CI 1.45-4.87). This interval was shorter in patients with a high PSA value (p = 0.012) and a high Gleason score (p = 0.026). CONCLUSIONS: Most incident prostate cancer patients in Spain are diagnosed at an early stage of an adenocarcinoma. The period to complete the diagnostic process is approximately three months whereas the therapeutic intervals vary among centres and are shorter for patients with a worse prognosis. The presence of prostatic symptoms, PSA level, and Gleason score influence all the clinical intervals differently. PMID- 26134120 TI - Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women. AB - Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd(3+)-sensitive, Na(+) dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na(+)-dependent leak current in human myometrium and demonstrate that the Na(+)-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca(2+) and K(+) channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 MUM Gd(3+) or by superfusing the cells with a Na(+)-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ~90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd(3+)-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability. PMID- 26134121 TI - Glutathione-induced drought stress tolerance in mung bean: coordinated roles of the antioxidant defence and methylglyoxal detoxification systems. AB - Drought is considered one of the most acute environmental stresses presently affecting agriculture. We studied the role of exogenous glutathione (GSH) in conferring drought stress tolerance in mung bean (Vigna radiata L. cv. Binamoog 1) seedlings by examining the antioxidant defence and methylglyoxal (MG) detoxification systems and physiological features. Six-day-old seedlings were exposed to drought stress (-0.7 MPa), induced by polyethylene glycol alone and in combination with GSH (1 mM) for 24 and 48 h. Drought stress decreased seedling dry weight and leaf area; resulted in oxidative stress as evidenced by histochemical detection of hydrogen peroxide (H2O2) and [Formula: see text] in the leaves; increased lipid peroxidation (malondialdehyde), reactive oxygen species like H2O2 content and [Formula: see text] generation rate and lipoxygenase activity; and increased the MG level. Drought decreased leaf succulence, leaf chlorophyll and relative water content (RWC); increased proline (Pro); decreased ascorbate (AsA); increased endogenous GSH and glutathione disulfide (GSSG) content; decreased the GSH/GSSG ratio; increased ascorbate peroxidase and glutathione S-transferase activities; and decreased the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and catalase. The activities of glyoxalase I (Gly I) and glyoxalase II (Gly II) increased due to drought stress. In contrast to drought stress alone, exogenous GSH enhanced most of the components of the antioxidant and glyoxalase systems in drought-affected mung bean seedlings at 24 h, but GSH did not significantly affect AsA, Pro, RWC, leaf succulence and the activities of Gly I and DHAR after 48 h of stress. Thus, exogenous GSH supplementation with drought significantly enhanced the antioxidant components and successively reduced oxidative damage, and GSH up-regulated the glyoxalase system and reduced MG toxicity, which played a significant role in improving the physiological features and drought tolerance. PMID- 26134122 TI - Effect of K+ and Ca2+ on the indole-3-acetic acid- and fusicoccin-induced growth and membrane potential in maize coleoptile cells. AB - The role of potassium (K(+)) and calcium (Ca(2+)) in the regulation of plant growth and development is complex and needs a diverse range of physiological studies. Both elements are essential for satisfactory crop production. Here, the effects of K(+) and Ca(2+) ions on endogenous growth and growth in the presence of either indole-3-acetic acid (IAA) or fusicoccin (FC) were studied in maize (Zea mays) coleoptiles. Membrane potentials of coleoptile parenchymal cells, incubated in media containing IAA, FC and different concentrations of K(+) and Ca(2+), were also determined. Growth experiments have shown that in the absence of K(+) in the incubation medium, both endogenous and IAA- or FC-induced growth were significantly inhibited by 0.1 and 1 mM Ca(2+), respectively, while in the presence of 1 mM K(+) they were inhibited only by 1 mM Ca(2+). At 10 mM K(+), endogenous growth and growth induced by either IAA or FC did not depend on Ca(2+) concentration. TEA-Cl, a potassium channel blocker, added 1 h before IAA or FC, caused a reduction of growth by 59 or 45 %, respectively. In contrast to TEA-Cl, verapamil, the Ca(2+) channel blocker, did not affect IAA- and FC-induced growth. It was also found that in parenchymal cells of maize coleoptile segments, membrane potential (Em) was strongly affected by the medium K(+), independently of Ca(2+). However, lack of Ca(2+) in the incubation medium significantly reduced the IAA- and FC-induced membrane potential hyperpolarization. TEA-Cl applied to the control medium in the same way as in growth experiments caused Em hyperpolarization synergistic with hyperpolarization produced by IAA or FC. Verapamil did not change either the Em of parenchymal cells incubated in the control medium or the IAA- and FC-induced membrane hyperpolarization. The data presented here have been discussed considering the role of K(+) uptake channels in regulation of plant cell growth. PMID- 26134123 TI - Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease. AB - Arterial stiffness is an independent determinant of cardiovascular risk and a marker of subclinical organ damage. Metabolomics may facilitate identification of novel low-molecular cardiovascular risk factors. The aim of the present study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects. We studied 42 men with symptomatic PAD (aged 66+/-7 years) and 46 healthy men (aged 66+/-8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass spectrometry. Serum oxidized low-density lipoprotein (oxLDL) level was measured by enzyme linked immunosorbent assay. The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. In contrast, serum levels of pyruvate, citrate, alpha-ketoglutarate, aconitate and cysteine were higher in the control group. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R(2)=0.61; P<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R(2)=0.52; P<0.001). Our study describes for the first time significant differences in metabolomic signature of patients with advanced atherosclerosis compared with clinically healthy controls. The aPWV is independently associated with serum levels of tyrosine and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers. PMID- 26134124 TI - Reassessment of data on timing peak flow-mediated vasodilatation confirms that endothelial function returns to normal 11 years after preeclampsia. PMID- 26134125 TI - Effect of N- and T-type calcium channel blocker on proteinuria, blood pressure and kidney function in hypertensive patients: a meta-analysis. AB - The combination of a calcium channel blocker (CCB) and a blocker of the renin angiotensin-aldosterone system (RAAS) is recommended in clinical practice guidelines. L/N- and L/T-type CCBs might provide an additional effect on lowering proteinuria. Therefore, we conducted a meta-analysis to assess the efficacy of L/N- and L/T-type CCBs in hypertensive patients with proteinuria. We searched MEDLINE, Scopus, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for single-arm studies and randomized controlled trials (RCTs) that examined the effect of L/N- and L/T-type CCBs as add-on therapy compared with standard antihypertensive regimen for proteinuria on hemodynamic and kidney related parameters in hypertensive patients with proteinuria. Random-effect model meta-analyses were used to compute changes in the outcomes of interest. We identified 17 RCTs, representing 1905 patients. By meta-analysis, L/N- and L/T type CCB add-on therapy did not yield significant changes in systolic and diastolic blood pressure compared with standard treatment, but there was a significant lowering of the pulse rate. However, L/N- and L/T-type CCBs resulted in a significant standardized net decrease in albuminuria and proteinuria (-1.01; 95% confidence interval (CI), -1.78 to -0.23; P=0.01), and a standardized net improvement in the estimated glomerular filtration rate and serum creatinine (0.23; 95% CI, 0.11 to 0.35, P<0.001; and -0.25; 95% CI, -0.46 to -0.03; P=0.02, respectively). Despite no additional lowering effect on blood pressure, L/N- and L/T-type CCBs combined with a blocker of the RAAS provided a decrease in proteinuria and improvement in kidney function. Further studies are required to establish the long-term kidney benefits of this combination therapy. PMID- 26134126 TI - Bilirubin exerts pro-angiogenic property through Akt-eNOS-dependent pathway. AB - Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3 kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner. PMID- 26134127 TI - Impact of depression on masked hypertension and variability in home blood pressure in treated hypertensive patients. AB - This study was conducted to determine the effects of depression and/or insomnia on masked hypertension (MHT) compared with other types of HT and on variability in home-measured blood pressure (HBP) and clinic BP (CBP). Three hundred and twenty-eight hypertensives (132 women) aged 68+/-10 years were classified into four BP types: controlled HT (CHT), white-coat HT, MHT and sustained HT (SHT), based on CBP (140/90 mm Hg) and morning HBP (135/85 mm Hg) measurements. A score of ?16 on the Center for Epidemiologic Studies Depression Scale (CES-D) was defined as depression. The mean values and s.d. of BP were calculated from measurements taken during the 14 consecutive days just before the CES-D evaluation. Compared with the CHT group, the risk of depression was 2.77-fold higher in the SHT group and even higher in the MHT group (7.02-fold). The association between depression and MHT was augmented in the presence of insomnia and was somewhat stronger in women. A HBP variability index defined as s.d./mean BPs in both morning and night time was significantly higher in MHT than in the other BP types, whereas that of CBP was not. Both morning and night-time HBP variability were significantly higher in depressive patients than in non depressives. These suggest that depression is associated with MHT and that increases both morning and night-time HBP variability but not CBP variability. Physicians should be mindful of mental stresses such as depression in their hypertensive patients when forming strategies to control BP over the diurnal cycle. PMID- 26134128 TI - Herpesvirus Genome Recognition Induced Acetylation of Nuclear IFI16 Is Essential for Its Cytoplasmic Translocation, Inflammasome and IFN-beta Responses. AB - The IL-1beta and type I interferon-beta (IFN-beta) molecules are important inflammatory cytokines elicited by the eukaryotic host as innate immune responses against invading pathogens and danger signals. Recently, a predominantly nuclear gamma-interferon-inducible protein 16 (IFI16) involved in transcriptional regulation has emerged as an innate DNA sensor which induced IL-1beta and IFN beta production through inflammasome and STING activation, respectively. Herpesvirus (KSHV, EBV, and HSV-1) episomal dsDNA genome recognition by IFI16 leads to IFI16-ASC-procaspase-1 inflammasome association, cytoplasmic translocation and IL-1beta production. Independent of ASC, HSV-1 genome recognition results in IFI16 interaction with STING in the cytoplasm to induce interferon-beta production. However, the mechanisms of IFI16-inflammasome formation, cytoplasmic redistribution and STING activation are not known. Our studies here demonstrate that recognition of herpesvirus genomes in the nucleus by IFI16 leads into its interaction with histone acetyltransferase p300 and IFI16 acetylation resulting in IFI16-ASC interaction, inflammasome assembly, increased interaction with Ran-GTPase, cytoplasmic redistribution, caspase-1 activation, IL 1beta production, and interaction with STING which results in IRF-3 phosphorylation, nuclear pIRF-3 localization and interferon-beta production. ASC and STING knockdowns did not affect IFI16 acetylation indicating that this modification is upstream of inflammasome-assembly and STING-activation. Vaccinia virus replicating in the cytoplasm did not induce nuclear IFI16 acetylation and cytoplasmic translocation. IFI16 physically associates with KSHV and HSV-1 genomes as revealed by proximity ligation microscopy and chromatin immunoprecipitation studies which is not hampered by the inhibition of acetylation, thus suggesting that acetylation of IFI16 is not required for its innate sensing of nuclear viral genomes. Collectively, these studies identify the increased nuclear acetylation of IFI16 as a dynamic essential post-genome recognition event in the nucleus that is common to the IFI16-mediated innate responses of inflammasome induction and IFN-beta production during herpesvirus (KSHV, EBV, HSV-1) infections. PMID- 26134129 TI - Expression and Characterization of the RKOD DNA Polymerase in Pichia pastoris. AB - The present study assessed high-level expression of the KOD DNA polymerase in Pichia pastoris. Thermococcus kodakaraensis KOD1 is a DNA polymerase that is widely used in PCR. The DNA coding sequence of KOD was optimized based on the codon usage bias of P. pastoris and synthesized by overlapping PCR, and the nonspecific DNA-binding protein Sso7d from the crenarchaeon Sulfolobus solfataricus was fused to the C-terminus of KOD. The resulting novel gene was cloned into a pHBM905A vector and introduced into P. pastoris GS115 for secretory expression. The yield of the target protein reached approximately 250 mg/l after a 6-d induction with 1% (v/v) methanol in shake flasks. This yield is much higher than those of other DNA polymerases expressed heterologously in Escherichia coli. The recombinant enzyme was purified, and its enzymatic features were studied. Its specific activity was 19,384 U/mg. The recombinant KOD expressed in P. pastoris exhibited excellent thermostability, extension rate and fidelity. Thus, this report provides a simple, efficient and economic approach to realize the production of a high-performance thermostable DNA polymerase on a large scale. This is the first report of the expression in yeast of a DNA polymerase for use in PCR. PMID- 26134130 TI - Ex Vivo Perfusion-Simulation Measurements of Microbubbles as a Scattering Contrast Agent for Grating-Based X-Ray Dark-Field Imaging. AB - The investigation of dedicated contrast agents for x-ray dark-field imaging, which exploits small-angle scattering at microstructures for contrast generation, is of strong interest in analogy to the common clinical use of high-atomic number contrast media in conventional attenuation-based imaging, since dark-field imaging has proven to provide complementary information. Therefore, agents consisting of gas bubbles, as used in ultrasound imaging for example, are of particular interest. In this work, we investigate an experimental contrast agent based on microbubbles consisting of a polyvinyl-alcohol shell with an iron oxide coating, which was originally developed for multimodal imaging and drug delivery. Its performance as a possible contrast medium for small-animal angiography was examined using a mouse carcass to realistically consider attenuating and scattering background signal. Subtraction images of dark field, phase contrast and attenuation were acquired for a concentration series of 100%, 10% and 1.3% to mimic different stages of dilution in the contrast agent in the blood vessel system. The images were compared to the gold-standard iodine-based contrast agent Solutrast, showing a good contrast improvement by microbubbles in dark-field imaging. This study proves the feasibility of microbubble-based dark-field contrast-enhancement in presence of scattering and attenuating mouse body structures like bone and fur. Therefore, it suggests a strong potential of the use of polymer-based microbubbles for small-animal dark-field angiography. PMID- 26134131 TI - Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting calreticulin expression in H9c2 cells. AB - Doxorubicin (DOX) is a potent and currently available antitumor therapeutic agent; however, its clinical application is limited by the occurrence of cardiotoxicity. Preliminary evidence indicates that hydrogen sulfide (H2S) may exert protective effects against DOX cardiotoxicity. Therefore, the aim of the present study was to investigate whether calreticulin (CRT) is involved in the cardioprotection of H2S against DOX-induced cardiotoxicity. DOX was observed to markedly induce injuries, including cytotoxicity and apoptosis, and also enhance the expression level of CRT. Notably, pretreatment of H9c2 cells with sodium hydrosulfide (a donor of H2S) significantly attenuated the decreased cell viability, the increased apoptosis rate and the increased expression level of CRT in H9c2 cells. In addition, pretreatment of H9c2 cells with N-acetyl-L-cysteine, a scavenger of reactive oxygen species (ROS) prior to exposure to DOX, markedly decreased the expression of CRT. These results indicate that exogenous H2S attenuates DOX-induced cardiotoxicity by inhibiting CRT expression in H9c2 cardiac cells. PMID- 26134132 TI - Revealing the toughening mechanism of graphene-polymer nanocomposite through molecular dynamics simulation. AB - By employing united atom molecular dynamics simulation, we have investigated the effects of polymer-graphene interaction epsilon(np) volume fraction of grapheme phi thermodynamics of polymer matrix (rubbery versus glassy), interfacial interaction in the case of the same dispersion state, shape of nanoparticles (NPs) such as C60 CNT and graphene at the same loading on the toughening efficiency of polymer nanocomposites. By beginning with the pure polymer, we observe that a plateau stress occurs at long chain length because entangled polymer chains in fibrils cannot become broken. We find that the work needed to dissipate during the failure increases with the increase of epsilon(np) and phi and the yield point in the stress-strain behavior occurs at a smaller strain for an attractive NPs filled system compared to the pure case, attributed to the more mechanically heterogeneous environment. The thermodynamics of the polymer matrix (below and above Tg) seems to have a significant effect on the toughening efficiency of graphene sheets. In the case of the same dispersion state, stronger interfacial interaction always induces long and highly orientated polymer fibrils along the deformation direction, with graphene sheets being encapsulated in these fiber-like bundles. By characterizing the interaction energy between polymer polymer and polymer-graphene as a function of the strain, we find that the separation of polymer chains from the graphene sheets cease immediately after the yield point, followed by the continuous propagation of the cavities by excluding surrounded polymer chains and graphene sheets together. We also find that at the same attractive interfacial interaction and same loading, the toughening efficiency exhibits the following order: graphene > CNT > C60 Generally, the toughening mechanism of graphene sheets results from the formation of long and highly orientated polymer fibrils to prevent the occurrence of the rupture, which can be greatly improved by the strong interfacial interaction and the large surface area compared to CNT and C60 This also indicates that polymer matrices with high flexibility and mobility of polymer chains tend to be better toughened. It is hoped that this simulation work will provide rational guidance for fabricating high performance of polymer nanocomposites with excellent toughness. PMID- 26134133 TI - Detection of Staphylococcus aureus enterotoxin production genes from patient samples using an automated extraction platform and multiplex real-time PCR. AB - To minimize specimen volume, handling and testing time, we have developed two TaqMan((r)) multiplex real-time PCR (rtPCR) assays to detect staphylococcal enterotoxins A-E and Toxic Shock Syndrome Toxin production genes directly from clinical patient stool specimens utilizing a novel lysis extraction process in parallel with the Roche MagNA Pure Compact. These assays are specific, sensitive and reliable for the detection of the staphylococcal enterotoxin encoding genes and the tst1 gene from known toxin producing strains of Staphylococcus aureus. Specificity was determined by testing a total of 47 microorganism strains, including 8 previously characterized staphylococcal enterotoxin producing strains against each rtPCR target. Sensitivity for these assays range from 1 to 25 cfu per rtPCR reaction for cultured isolates and 8-20 cfu per rtPCR for the clinical stool matrix. PMID- 26134134 TI - Multiple scale model for cell migration in monolayers: Elastic mismatch between cells enhances motility. AB - We propose a multiscale model for monolayer of motile cells that comprise normal and cancer cells. In the model, the two types of cells have identical properties except for their elasticity; cancer cells are softer and normal cells are stiffer. The goal is to isolate the role of elasticity mismatch on the migration potential of cancer cells in the absence of other contributions that are present in real cells. The methodology is based on a phase-field description where each cell is modeled as a highly-deformable self-propelled droplet. We simulated two types of nearly confluent monolayers. One contains a single cancer cell in a layer of normal cells and the other contains normal cells only. The simulation results demonstrate that elasticity mismatch alone is sufficient to increase the motility of the cancer cell significantly. Further, the trajectory of the cancer cell is decorated by several speed "bursts" where the cancer cell quickly relaxes from a largely deformed shape and consequently increases its translational motion. The increased motility and the amplitude and frequency of the bursts are in qualitative agreement with recent experiments. PMID- 26134135 TI - Atherosclerotic Plaque Analysis: A Pilot Study to Assess a Novel Tool to Predict Outcome Following Lower Limb Endovascular Intervention. AB - INTRODUCTION: Atherosclerotic plaque analysis using computed tomography angiography (CTA) has been found to be accurate and reproducible in the coronary and carotid arteries. The aim of our study was to assess the utility of this technique in predicting outcome following lower limb endovascular interventions. METHODS: Pre-procedural CTA was retrospectively analysed in 50 patients who had undergone femoropopliteal (F-P) angioplasty (and/or stenting). Plaque analysis was performed using TeraRecon workstation by two observers blinded to the long term outcome. Using the Hounsfield units (HU) scale atherosclerotic plaque composition was subdivided into volumes of soft (-100-100 HU) fibrocalcific (101 300 HU) or calcified (300-1000 HU) components. The relationship between plaque composition, clinical and procedural variables, and the study end points (vessel patency, binary restenosis rate, and Amputation-Free Survival [AFS]) were assessed using multivariate analysis. RESULTS: The technical success rate of the endovascular procedure was 98%, with 48% of patients receiving F-P stents. The AFS was 90%, primary patency 84%, assisted primary patency 88%, and binary restenosis 44% all at 1 year. A significantly greater total volume of calcified plaque (1.1 [.01-3.2] cm(3) vs. .11 [0-1.86] cm(3), p < .001) was found in patients developing restenosis (>50%) compared with those who did not. Patients with a calcified plaque volume greater than 1.1 cm(3) had a significantly worse AFS than those with a volume less than 1.1 cm(3) (p = .0038). Multivariate analysis showed that the percentage calcified plaque (p = .003, HR 11.4, 95% CI 1.45-37.29) was an independent predictor of binary restenosis at 12 months, and that absolute volume of calcified plaque (p = .001, HR 3.56, 95% CI 1.64-7.7) was independently associated with AFS. CONCLUSIONS: The burden of calcified plaque, but not soft or fibrocalcific plaque is related to restenosis, reintervention, and AFS. Computed tomography plaque analysis may form an important non-invasive tool for risk stratification in patients undergoing F-P endovascular procedures. PMID- 26134136 TI - Molecular properties of diacylglycerol kinase-epsilon in relation to function. AB - The epsilon isoform of mammalian diacylglycerol kinase (DGKepsilon) is an enzyme that associates strongly with membranes and acts on a lipid substrate, diacylglycerol. The protein has one segment that is predicted to be a transmembrane helix, but appears to interconvert between a transmembrane helix and a re-entrant helix. Despite the hydrophobicity of this segment and the fact that the lipid substrate is also hydrophobic, removal of this hydrophobic segment by truncating the protein at the amino terminus has no effect on its enzymatic activity. The amino acid sequence of the catalytic segment of DGKepsilon is highly homologous to that of a bacterial DGK, DgkB. This has allowed us to predict a conformation of DGKepsilon based on the known crystal structure of DgkB. An important property of DGKepsilon is that it is specific for diacylglycerol species containing an arachidonoyl group. The region of DGKepsilon that interacts with this group is found within the accessory domain of the protein and not in the active site nor in the hydrophobic amino terminus. The nature of the acyl chain specificity of the enzyme indicates that DGKepsilon is associated with the synthesis of phosphatidylinositol. Defects or deletion of the enzyme give rise to several disease states. PMID- 26134137 TI - Novel sulfated phosphoglycolipids from Natronomonas moolapensis. AB - Polar lipid pattern determination is often used for the taxonomic classification of halophilic Archaea in addition to a genomic characterization. During the analysis of polar lipid extracts from the recently described haloarchaeon Natrononomonas moolapensis, an unknown glycolipid was detected. Fragmentation patterns observed from preliminary mass spectrometric analysis initially suggested the presence of a sulfo-hexosyl-phosphatidylglycerol. However, by NMR spectroscopy and enzymatic assays the existence of two isomeric molecules with different hexoses (1-(6-sulfo-d-glcp/galf-beta1,2-glycero)-phospho-2,3 diphytanylglycerol) could be shown. The structural origin from phosphatidylglycerol distinguishes these glycolipids within Archaea, because all other characterized haloarchaeal glycolipids consist of diphytanylglycerol directly linked to an oligoglycosyl moiety. Now the door is open to investigate the physical and functional consequences of these architectural differences of the head groups. PMID- 26134139 TI - Affiliative Subgroups in Preschool Classrooms: Integrating Constructs and Methods from Social Ethology and Sociometric Traditions. AB - Recent studies of school-age children and adolescents have used social network analyses to characterize selection and socialization aspects of peer groups. Fewer network studies have been reported for preschool classrooms and many of those have focused on structural descriptions of peer networks, and/or, on selection processes rather than on social functions of subgroup membership. In this study we started by identifying and describing different types of affiliative subgroups (HMP- high mutual proximity, LMP- low mutual proximity, and ungrouped children) in a sample of 240 Portuguese preschool children using nearest neighbor observations. Next, we used additional behavioral observations and sociometric data to show that HMP and LMP subgroups are functionally distinct: HMP subgroups appear to reflect friendship relations, whereas LMP subgroups appear to reflect common social goals, but without strong, within subgroup dyadic ties. Finally, we examined the longitudinal implications of subgroup membership and show that children classified as HMP in consecutive years had more reciprocated friendships than did children whose subgroup classification changed from LMP or ungrouped to HMP. These results extend previous findings reported for North American peer groups. PMID- 26134138 TI - De novo Transcriptome Assembly of Common Wild Rice (Oryza rufipogon Griff.) and Discovery of Drought-Response Genes in Root Tissue Based on Transcriptomic Data. AB - BACKGROUND: The perennial O. rufipogon (common wild rice), which is considered to be the ancestor of Asian cultivated rice species, contains many useful genetic resources, including drought resistance genes. However, few studies have identified the drought resistance and tissue-specific genes in common wild rice. RESULTS: In this study, transcriptome sequencing libraries were constructed, including drought-treated roots (DR) and control leaves (CL) and roots (CR). Using Illumina sequencing technology, we generated 16.75 million bases of high quality sequence data for common wild rice and conducted de novo assembly and annotation of genes without prior genome information. These reads were assembled into 119,332 unigenes with an average length of 715 bp. A total of 88,813 distinct sequences (74.42% of unigenes) significantly matched known genes in the NCBI NT database. Differentially expressed gene (DEG) analysis showed that 3617 genes were up-regulated and 4171 genes were down-regulated in the CR library compared with the CL library. Among the DEGs, 535 genes were expressed in roots but not in shoots. A similar comparison between the DR and CR libraries showed that 1393 genes were up-regulated and 315 genes were down-regulated in the DR library compared with the CR library. Finally, 37 genes that were specifically expressed in roots were screened after comparing the DEGs identified in the above described analyses. CONCLUSION: This study provides a transcriptome sequence resource for common wild rice plants and establishes a digital gene expression profile of wild rice plants under drought conditions using the assembled transcriptome data as a reference. Several tissue-specific and drought-stress related candidate genes were identified, representing a fully characterized transcriptome and providing a valuable resource for genetic and genomic studies in plants. PMID- 26134140 TI - Effectiveness of antibacterial prophylaxis with non-absorbable polymyxin B compared to levofloxacin after allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: Fluoroquinolones are widely used for antibacterial prophylaxis during neutropenia following hematopoietic stem cell transplantation (HSCT). Nevertheless, data are inadequate as to whether fluoroquinolones decrease mortality rate compared with other antibiotics. METHODS: We retrospectively compared the efficacy of antibacterial prophylaxis using non-absorbable polymyxin B (PB) (n = 106) or systemic levofloxacin (LVFX) (n = 140) after allogeneic SCT at our institute between 2004 and 2013. RESULTS: No significant difference was observed between the 2 groups in the cumulative incidences of failure of prophylaxis (P = 0.21), clinically documented infections (P = 0.70), or non relapse mortality within the first 100 days after transplantation (P = 0.42). With bacteremia, the rate of resistance to LVFX was 82% in the PB group and 100% in the LVFX group (P = 0.41). Also, no significant difference was found in overall survival between the 2 groups (P = 0.78). CONCLUSION: Our results indicate no difference in the effectiveness of antibacterial prophylaxis between systemic antibiotic LVFX and non-absorbable antibiotic PB. PMID- 26134141 TI - In Vivo Profiling Reveals a Competent Heat Shock Response in Adult Neurons: Implications for Neurodegenerative Disorders. AB - The heat shock response (HSR) is the main pathway used by cells to counteract proteotoxicity. The inability of differentiated neurons to induce an HSR has been documented in primary neuronal cultures and has been proposed to play a critical role in ageing and neurodegeneration. However, this accepted dogma has not been demonstrated in vivo. We used BAC transgenic mice generated by the Gene Expression Nervous System Atlas project to investigate the capacity of striatal medium sized spiny neurons to induce an HSR as compared to that of astrocytes and oligodendrocytes. We found that all cell populations were competent to induce an HSR upon HSP90 inhibition. We also show the presence and relative abundance of heat shock-related genes and proteins in these striatal cell populations. The identification of a competent HSR in adult neurons supports the development of therapeutics that target the HSR pathway as treatments for neurodegenerative disorders. PMID- 26134142 TI - An exposure-weighted score test for genetic associations integrating environmental risk factors. AB - Current methods for detecting genetic associations lack full consideration of the background effects of environmental exposures. Recently proposed methods to account for environmental exposures have focused on logistic regressions with gene-environment interactions. In this report, we developed a test for genetic association, encompassing a broad range of risk models, including linear, logistic and probit, for specifying joint effects of genetic and environmental exposures. We obtained the test statistics by maximizing over a class of score tests, each of which involves modified standard tests of genetic association through a weight function. This weight function reflects the potential heterogeneity of the genetic effects by levels of environmental exposures under a particular model. Simulation studies demonstrate the robust power of these methods for detecting genetic associations under a wide range of scenarios. Applications of these methods are further illustrated using data from genome-wide association studies of type 2 diabetes with body mass index and of lung cancer risk with smoking. PMID- 26134143 TI - Dichroic spin-valley photocurrent in monolayer molybdenum disulphide. AB - The aim of valleytronics is to exploit confinement of charge carriers in local valleys of the energy bands of semiconductors as an additional degree of freedom in optoelectronic devices. Thanks to strong direct excitonic transitions in spin coupled K valleys, monolayer molybdenum disulphide is a rapidly emerging valleytronic material, with high valley polarization in photoluminescence. Here we elucidate the excitonic physics of this material by light helicity-dependent photocurrent studies of phototransistors. We demonstrate that large photocurrent dichroism (up to 60%) can also be achieved in high-quality molybdenum disulphide monolayers grown by chemical vapour deposition, due to the circular photogalvanic effect on resonant excitations. This opens up new opportunities for valleytonic applications in which selective control of spin-valley-coupled photocurrents can be used to implement polarization-sensitive light-detection schemes or integrated spintronic devices, as well as biochemical sensors operating at visible frequencies. PMID- 26134144 TI - GPCRtm: An amino acid substitution matrix for the transmembrane region of class A G Protein-Coupled Receptors. AB - BACKGROUND: Protein sequence alignments and database search methods use standard scoring matrices calculated from amino acid substitution frequencies in general sets of proteins. These general-purpose matrices are not optimal to align accurately sequences with marked compositional biases, such as hydrophobic transmembrane regions found in membrane proteins. In this work, an amino acid substitution matrix (GPCRtm) is calculated for the membrane spanning segments of the G protein-coupled receptor (GPCR) rhodopsin family; one of the largest transmembrane protein family in humans with great importance in health and disease. RESULTS: The GPCRtm matrix reveals the amino acid compositional bias distinctive of the GPCR rhodopsin family and differs from other standard substitution matrices. These membrane receptors, as expected, are characterized by a high content of hydrophobic residues with regard to globular proteins. On the other hand, the presence of polar and charged residues is higher than in average membrane proteins, displaying high frequencies of replacement within themselves. CONCLUSIONS: Analysis of amino acid frequencies and values obtained from the GPCRtm matrix reveals patterns of residue replacements different from other standard substitution matrices. GPCRs prioritize the reactivity properties of the amino acids over their bulkiness in the transmembrane regions. A distinctive role is that charged and polar residues seem to evolve at different rates than other amino acids. This observation is related to the role of the transmembrane bundle in the binding of ligands, that in many cases involve electrostatic and hydrogen bond interactions. This new matrix can be useful in database search and for the construction of more accurate sequence alignments of GPCRs. PMID- 26134145 TI - Erlotinib and gefitinib for treating non-small cell lung cancer that has progressed following prior chemotherapy (review of NICE technology appraisals 162 and 175): a systematic review and economic evaluation. AB - BACKGROUND: Lung cancer is the second most diagnosed cancer in the UK. Over 70% of lung cancers are non-small cell lung cancers (NSCLCs). Patients with stage III or IV NSCLC may be offered treatment to improve survival, disease control and quality of life. One-third of these patients receive further treatment following disease progression; these treatments are the focus of this systematic review. OBJECTIVES: To appraise the clinical effectiveness and cost-effectiveness of erlotinib [Tarceva((r)), Roche (UK) Ltd] and gefitinib (IRESSA((r)), AstraZeneca) compared with each other, docetaxel or best supportive care (BSC) for the treatment of NSCLC after disease progression following prior chemotherapy. The effectiveness of treatment with gefitinib was considered only for patients with epidermal growth factor mutation-positive (EGFR M+) disease. DATA SOURCES: Four electronic databases (EMBASE, MEDLINE, The Cochrane Library, PubMed) were searched for randomised controlled trials (RCTs) and economic evaluations. Manufacturers' evidence submissions to the National Institute for Health and Care Excellence were also considered. REVIEW METHODS: Outcomes for three distinct patient groups based on EGFR mutation status [EGFR M+, epidermal growth factor mutation negative (EGFR M-) and epidermal growth factor mutation status unknown (EGFR unknown)] were considered. Heterogeneity of the data precluded statistical analysis. A de novo economic model was developed to compare treatments (incremental cost per quality-adjusted life-year gained). RESULTS: Twelve trials were included in the review. The use of gefitinib was compared with chemotherapy (n = 6) or BSC (n = 1), and the use of erlotinib was compared with chemotherapy (n = 3) or BSC (n = 1). One trial compared the use of gefitinib with the use of erlotinib. No trials included solely EGFR M+ patients; all data were derived from retrospective subgroup analyses from six RCTs [Kim ST, Uhm JE, Lee J, Sun JM, Sohn I, Kim SW, et al. Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy. Lung Cancer 2012;75:82-8, V-15-32, Tarceva In Treatment of Advanced NSCLC (TITAN), BR.21, IRESSA Survival Evaluation in Lung cancer (ISEL) and IRESSA NSCLC Trial Evaluating REsponse and Survival versus Taxotere (INTEREST)]. These limited data precluded conclusions regarding the clinical effectiveness of any treatment for EGFR M+ patients. For EGFR M- patients, data were derived from the TArceva Italian Lung Optimization tRial (TAILOR) trial and Docetaxel and Erlotinib Lung Cancer Trial (DELTA). Retrospective data were also derived from subgroup analyses of BR.21, Kim et al., TITAN, INTEREST and ISEL. The only statistically significant reported results were for progression-free survival (PFS) for TAILOR and DELTA, and favoured docetaxel over erlotinib [TAILOR hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.06 to 1.82; DELTA HR 1.44, 95% CI 1.08 to 1.92]. In EGFR unknown patients, nine trials (INTEREST, IRESSA as Second line Therapy in Advanced NSCLC - KoreA, Li, Second-line Indication of Gefitinib in NSCLC, V-15-32, ISEL, DELTA, TITAN and BR.21) reported overall survival data and only one (BR.21) reported a statistically significant result favouring the use of erlotinib over BSC (HR 0.7, 95% CI 0.58 to 0.85). For PFS, BR.21 favoured the use of erlotinib when compared with BSC (HR 0.61, 95% CI 0.51 to 0.74) and the use of gefitinib was favoured when compared with BSC (HR 0.82, 95% CI 0.73 to 0.92) in ISEL. Limitations in the clinical data precluded assessment of cost effectiveness of treatments for an EGFR M+ population by the Assessment Group (AG). The AG's economic model suggested that for the EGFR M- population, the use of erlotinib was not cost-effective compared with the use of docetaxel and compared with BSC. For EGFR unknown patients, the use of erlotinib was not cost effective when compared with BSC. CONCLUSIONS/FUTURE WORK: The lack of clinical data available for distinct patient populations limited the conclusions of the assessment. Future trials should distinguish between patients with EGFR M+ and EGFR M- disease. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26134146 TI - Corrosion scales and passive films: general discussion. PMID- 26134149 TI - Reply: To PMID 25596171. PMID- 26134150 TI - Surface modification of alumina-coated silica nanoparticles in aqueous sols with phosphonic acids and impact on nanoparticle interactions. AB - It is often necessary to tailor nanoparticle (NP) interactions and their compatibility with a polymer matrix by grafting organic groups, but the commonly used silanization route offers little versatility, particularly in water. Herein, alumina-coated silica NPs in aqueous sols have been modified for the first time with low molecular-weight phosphonic acids (PAs) bearing organic groups of various hydrophobicities and charges: propyl, pentyl and octyl PAs, and two PAs bearing hydrophilic groups, either a neutral diethylene glycol (DEPA) or a potentially charged carboxylic acid (CAPA) group. The interactions and aggregation in the sols have been investigated using zeta potential measurements, dynamic light scattering, transmission electron microscopy, and small-angle scattering methods. The surface modification has been studied using FTIR and (31)P MAS NMR spectroscopies. Both high grafting density rho and high hydrophobicity of the groups on the PAs induced aggregation, whereas suspensions of NPs grafted by DEPA remained stable up to the highest rho. Unexpectedly, CAPA modified NPs showed aggregation even at low rho, suggesting that the carboxylic end group was also grafted to the surface. Surface modification of aqueous sols with PAs allows thus for the grafting of a higher density and a wider variety of organic groups than organosilanes, offering an increased control of the interactions between NPs, which is of interest for designing waterborne nanocomposites. PMID- 26134148 TI - Uncovering miRNAs involved in crosstalk between nutrient deficiencies in Arabidopsis. AB - Integrating carbon (C), nitrogen (N), and sulfur (S) metabolism is essential for the growth and development of living organisms. MicroRNAs (miRNAs) play key roles in regulating nutrient metabolism in plants. However, how plant miRNAs mediate crosstalk between different nutrient metabolic pathways is unclear. In this study, deep sequencing of Arabidopsis thaliana small RNAs was used to reveal miRNAs that were differentially expressed in response to C, N, or S deficiency. Comparative analysis revealed that the targets of the differentially expressed miRNAs are involved in different cellular responses and metabolic processes, including transcriptional regulation, auxin signal transduction, nutrient homeostasis, and regulation of development. C, N, and S deficiency specifically induced miR169b/c, miR826 and miR395, respectively. In contrast, miR167, miR172, miR397, miR398, miR399, miR408, miR775, miR827, miR841, miR857, and miR2111 are commonly suppressed by C, N, and S deficiency. In particular, the miRNAs that are induced specifically by a certain nutrient deficiency are often suppressed by other nutrient deficiencies. Further investigation indicated that the modulation of nutrient-responsive miRNA abundance affects the adaptation of plants to nutrient starvation conditions. This study revealed that miRNAs function as important regulatory nodes of different nutrient metabolic pathways. PMID- 26134151 TI - Coincidence of superficial brachiomedian artery and bitendinous palmaris longus: a case report. AB - We present a unique unilateral case of a superficial brachiomedian artery that coincides with a variable palmaris longus muscle in a male cadaver. The superficial brachiomedian artery branched at the distal part of the right arm and coursed superficially in the cubital and antebrachial regions. Then it passed through the carpal canal and formed a complete superficial palmar arch by joining the trunk of the ulnar artery. The variable bitendinous palmaris longus was composed of a central belly and two asymmetrical tendons inserting mainly on the ulnar side of the flexor retinaculum. The knowledge of this arterial variant is of high clinical relevance for the catheterization, for the harvesting of the forearm artery as a graft, for the collateral circulation in cases of arterial occlusion, for surgical management of the carpal tunnel syndrome, or in cases of injury of the superficially located variant artery. PMID- 26134153 TI - Correction: Synthesis of 2-deoxy-2,2-difluoro-alpha-maltosyl fluoride and its X ray structure in complex with Streptomyces coelicolor GlgEI-V279S. AB - Correction for 'Synthesis of 2-deoxy-2,2-difluoro-alpha-maltosyl fluoride and its X-ray structure in complex with Streptomyces coelicolor GlgEI-V279S' by Sandeep Thanna et al., Org. Biomol. Chem., 2015, DOI: 10.1039/c5ob00867k. PMID- 26134152 TI - Circulating miR-103 and miR-720 as novel serum biomarkers for patients with colorectal cancer. AB - Circulating microRNAs (miRNAs) have been reported as a biomarker for human malignancies, including colorectal cancer (CRC). The purpose of this study was to identify a novel biomarker for CRC through examination of serum miRNAs from the patients with CRC. Microarray analysis of miRNA expression was performed using paired pre- and post-operative serum from 10 CRC patients. miR-103 and miR-720 decreased significantly in the post-operative serum when compared to pre operative serum. With an extended scale validation by qRT-PCR (quantitative real time polymerase chain reaction) in 30 CRC patients, we confirmed that serum miR 103 and miR-720 decreased significantly after surgery (P=0.0004, and P=0.0274, respectively). Next, we examined serum miR-103 and miR-720 levels in 32 non cancer patients and 84 CRC patients, and we found that expression of these two miRNAs was significantly higher in CRC patients than non-cancer patients. Furthermore, clinical and pathological survey indicated that high expression of miR-103 was significantly associated with histological differentiation grade, and lymphatic invasion and high expression of miR-720 was significantly associated with male gender and lymph node metastasis. Our data suggest that circulating miR 103 and miR-720 show potential as novel serum biomarkers for CRC. PMID- 26134155 TI - Disposition and metabolism of cabotegravir: a comparison of biotransformation and excretion between different species and routes of administration in humans. AB - 1. Cabotegravir [(3S,11aR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7 dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8 carboxamide] is an HIV-1 integrase inhibitor under development as a tablet for both oral lead-in therapy and long-acting (LA) injectable for intramuscular dosing. 2. Metabolism, pharmacokinetics and excretion were investigated in healthy human subjects who received either a single oral dose (28.2 mg) of [(14)C]cabotegravir in a mass balance study, or LA formulations of unlabeled cabotegravir (200-800 mg), intramuscularly or subcutaneously, in a separate study. Metabolism, distribution and excretion of [(14)C]cabotegravir were also investigated in mice, rats and monkeys. 3. Recovery of radioactivity in humans represented a mean total of 85.3% of the dose, including 26.8% in the urine. The mean apparent terminal phase half-life was similar for both cabotegravir and radioactivity, 39 h compared to 41 h. 4. Following oral, intramuscular and subcutaneous administration, cabotegravir was the major component in plasma and the glucuronic acid conjugate (M1) represented the predominant component in urine. Cabotegravir was present in bile along with its major metabolite (M1). 5. The primary metabolite of [(14)C]cabotegravir in mouse, rat and monkey was the same as that in human. In vitro phenotyping experiments demonstrated that cabotegravir was metabolized by UDP-glucuronosyltransferase (UGT) 1A1 and UGT1A9. PMID- 26134154 TI - Elevated BP after AKI. AB - The connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP--defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit--during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization. PMID- 26134156 TI - MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy. AB - Radioresistance has become a challenge in the treatment of pancreatic cancer, which limits the efficacy and outcomes of radiotherapy in clinical treatment. Autophagy, recognized as an adaptive response to cell stress, has recently been involved in the radioresistance of cancer cells. MicroRNAs (miRNAs) are also involved in the radioresistance of pancreatic cancer cells. In the present study, we established a radioresistant pancreatic cancer cell line and found that miRNA 216a was significantly downregulated whereas the autophagy activity was increased as compared with the control. Forced expression of miR-216a was found to inhibit the expression of beclin-1, a critical autophagic gene, as well as autophagy. Using bioinformatics analysis and the dual-luciferase reporter gene assay, we found that miR-216a directly interacted with 3'-untranslated region (UTR) of beclin-1. Furthermore, the forced expression of miR-216a inhibited cell growth and colony formation ability and promoted the cell apoptosis of radioresistant pancreatic cancer cells in response to irradiation. By contrast, overexpression of beclin-1 abrogated the effects of miR-216a. Furthermore, miR-216a sensitized xenograft tumor to irradiation treatment and inhibited irradiation-induced autophagy by regulating beclin-1. Collectively, the results demonstrated that miR 216a enhanced the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy, suggesting a promising molecular target for improving the radiotherapy of pancreatic cancer. PMID- 26134157 TI - Efficacy and safety profile of prolonged release oxycodone in combination with naloxone (OXN PR) in Parkinson's disease patients with chronic pain. AB - Pain is a relevant and often underestimated non-motor symptom affecting the quality of life of patients with Parkinson's disease (PD). Although some pain symptoms can be effectively treated by dopaminergic medication, a correct diagnosis of the different types and distribution of pain in PD is challenging, and accordingly, its treatment remains troublesome. We evaluated the efficacy and the safety of a prolonged release oral formulation of oxycodone hydrochloride combined with naloxone hydrochloride dehydrate, in a fixed ratio of 2:1 (OXN PR). A total of 16 PD patients with history of pain with a minimum intensity of four on numerical rating scale (NRS) received low-dose OXN PR (5/2.5 mg twice daily) and were observed for a period of 8 weeks. The primary efficacy measure was the pain severity measured with NRS and Brief Pain Inventory (BPI). Secondary efficacy measured the safety profile by recording the occurrence of side effects, clinical global impression of change (CGI-C), Parkinson's disease sleep scale 2 (PDSS-2), Bowel function index (BFI). Data were collected and analyzed using descriptive statistics. Patients who completed the study (14 out of 16) reported a significant pain relief as observed by the reduction of NRS and BPI scores. No adjustment of dopaminergic therapy was required. No significant changes were observed in bowel function and constipation symptoms as measured by the BFI during the 8-week period. Similarly, no changes were observed in PDSS-2 score, whereas an improvement was recorded by CGI-C compared to baseline. Low-dose oral OXN PR was efficacious for the management of pain symptoms of patients with PD. More importantly, patients did not experience significant side effects, such as constipation or sedation. Our study provides evidence that opioids can be used to treat pain symptoms in PD patients. PMID- 26134158 TI - Echocardiography in the diagnosis of patients with absent pulmonary valve syndrome: a review study of 12 years. AB - Absent pulmonary valve syndrome (APVS) is a rare congenital heart disease that is easily misdiagnosed as tetralogy of Fallot (TOF). We herein discuss the echocardiographic features of APVS, compare its two subtypes, and clarify some differences between APVS and TOF. From July 1998 to October 2011, 31 patients diagnosed with APVS at Fuwai Hospital underwent echocardiography, computed tomography, or cardiac angiography. APVS was clinically categorized as either infant-type or child-type. We compared the echocardiographic similarities and differences between APVS and TOF and between the two subtypes of APVS. Although enlargement or aneurysmal dilatation was present in the main pulmonary artery (PA) and its branch in most patients, pulmonary dysplasia or even an absent left PA was found in a few patients. Four important echocardiographic features of APVS useful for distinguishing this syndrome from TOF were (1) absence of the pulmonary valve or presence of pulmonary valve dysplasia, (2) concurrent stenosis and regurgitation at the pulmonary annulus, (3) significant aneurysmal dilatation in the areas of the PAs, and (4) increased rather than decreased PA pressure. 10 patients had infant-type APVS and 21 had child-type APVS. Compared with child type APVS, infant-type APVS was usually characterized by a lower oxygen saturation, more dilated main PA and right PA, lower aorta-PA ratio, higher diastolic PA pressure, and lower incidence of an absent left PA. Echocardiography is important for diagnosing APVS and distinguishing it from TOF. There are minimal differences in the echocardiographic features between infant-type and child-type APVS. PMID- 26134160 TI - Measuring 'virtue' in medicine. AB - Virtue-approaches to medical ethics are becoming ever more influential. Virtue theorists advocate redefining right or good action in medicine in terms of the character of the doctor performing the action (rather than adherence to rules or principles). In medical education, too, calls are growing to reconceive medical education as a form of character formation (rather than instruction in rules or principles). Empirical studies of doctors' ethics from a virtue-perspective, however, are few and far between. In this respect, theoretical and empirical study of medical ethics are out of alignment. In this paper, we survey the empirical study of medical ethics and find that most studies of doctors' ethics are rules- or principles-based and not virtue-based. We outline the challenges that exist for studying medical ethics empirically from a virtue-based perspective and canvas the runners and riders in the effort to find virtue-based assessments of medical ethics. PMID- 26134159 TI - Coronary computed tomography angiography for the assessment of chest pain: current status and future directions. AB - Chest pain is one of the most common presenting symptoms leading to presentation to medical clinics and Emergency Departments worldwide. Defining the nature and etiology of chest pain can pose a diagnostic dilemma for clinicians, despite the availability of several diagnostic algorithms and guidelines to assist them in evaluating these patients. Most investigations in patients with acute chest pain are initially performed to either exclude or diagnose and manage potentially life threatening conditions such as acute coronary syndrome, pulmonary embolism and aortic dissection. In cases of stable chest pain syndromes, the focus shifts to determining the presence, extent and severity of coronary artery disease. In recent years, coronary computed tomography angiography (CCTA) is being increasingly used worldwide in the assessment of both stable and acute chest pain syndromes. This review evaluates the current evidence regarding the clinical utility of CCTA in the stable and acute chest pain settings and outlines the latest advances in CCTA techniques, including functional assessment of coronary stenoses, and their potential clinical application to improve patient care in a cost-effective manner. PMID- 26134161 TI - The Soybean-Specific Maturity Gene E1 Family of Floral Repressors Controls Night Break Responses through Down-Regulation of FLOWERING LOCUS T Orthologs. AB - Photoperiodism is a rhythmic change of sensitivity to light, which helps plants to adjust flowering time according to seasonal changes in daylength and to adapt to growing conditions at various latitudes. To reveal the molecular basis of photoperiodism in soybean (Glycine max), a facultative short-day plant, we analyzed the transcriptional profiles of the maturity gene E1 family and two FLOWERING LOCUS T (FT) orthologs (FT2a and FT5a). E1, a repressor for FT2a and FT5a, and its two homologs, E1-like-a (E1La) and E1Lb, exhibited two peaks of expression in long days. Using two different approaches (experiments with transition between light and dark phases and night-break experiments), we revealed that the E1 family genes were expressed only during light periods and that their induction after dawn in long days required a period of light before dusk the previous day. In the cultivar Toyomusume, which lacks the E1 gene, virus induced silencing of E1La and E1Lb up-regulated the expression of FT2a and FT5a and led to early flowering. Therefore, E1, E1La, and E1Lb function similarly in flowering. Regulation of E1 and E1L expression by light was under the control of E3 and E4, which encode phytochrome A proteins. Our data suggest that phytochrome A-mediated transcriptional induction of E1 and its homologs by light plays a critical role in photoperiodic induction of flowering in soybean. PMID- 26134162 TI - Producing the Ethylene Signal: Regulation and Diversification of Ethylene Biosynthetic Enzymes. AB - Strictly controlled production of ethylene gas lies upstream of the signaling activities of this crucial regulator throughout the plant life cycle. Although the biosynthetic pathway is enzymatically simple, the regulatory circuits that modulate signal production are fine tuned to allow integration of responses to environmental and intrinsic cues. Recently identified posttranslational mechanisms that control ethylene production converge on one family of biosynthetic enzymes and overlay several independent reversible phosphorylation events and distinct mediators of ubiquitin-dependent protein degradation. Although the core pathway is conserved throughout seed plants, these posttranslational regulatory mechanisms may represent evolutionarily recent innovations. The evolutionary origins of the pathway and its regulators are not yet clear; outside the seed plants, numerous biochemical and phylogenetic questions remain to be addressed. PMID- 26134163 TI - Subtle Regulation of Potato Acid Invertase Activity by a Protein Complex of Invertase, Invertase Inhibitor, and SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE. AB - Slowing down cold-induced sweetening (CIS) of potato (Solanum tuberosum) tubers is of economic importance for the potato industry to ensure high-quality products. The conversion of sucrose to reducing sugars by the acid invertase StvacINV1 is thought to be critical for CIS. Identification of the specific StvacINV1 inhibitor StInvInh2B and the alpha- and beta-subunits of the interacting protein SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE from the wild potato species Solanum berthaultii (SbSnRK1) has led to speculation that invertase activity may be regulated via a posttranslational mechanism that remains to be elucidated. Using bimolecular fluorescence complementation assays, this study confirmed the protein complex by pairwise interactions. In vitro kinase assays and protein phosphorylation analysis revealed that phosphorylation of SbSnRK1alpha is causal for StvacINV1 activity and that its active form blocks the inhibition of StInvInh2B by SbSnRK1beta, whereas its inactive form restores the function of SbSnRK1beta that prevents StInvInh2B from repressing StvacINV1. Overexpression of SbSnRK1alpha in CIS-sensitive potato confirmed that SbSnRK1alpha has significant effects on acid invertase-associated sucrose degradation. A higher level of SbSnRK1alpha expression was accompanied by elevated SbSnRK1alpha phosphorylation, reduced acid invertase activity, a higher sucrose-hexose ratio, and improved chip color. Our results lend new insights into a subtle regulatory mode of invertase activity and provide a novel approach for potato CIS improvement. PMID- 26134164 TI - Complete Mitochondrial Complex I Deficiency Induces an Up-Regulation of Respiratory Fluxes That Is Abolished by Traces of Functional Complex I. AB - Complex I (NADH:ubiquinone oxidoreductase) is central to cellular NAD(+) recycling and accounts for approximately 40% of mitochondrial ATP production. To understand how complex I function impacts respiration and plant development, we isolated Arabidopsis (Arabidopsis thaliana) lines that lack complex I activity due to the absence of the catalytic subunit NDUFV1 (for NADH:ubiquinone oxidoreductase flavoprotein1) and compared these plants with ndufs4 (for NADH:ubiquinone oxidoreductase Fe-S protein4) mutants possessing trace amounts of complex I. Unlike ndufs4 plants, ndufv1 lines were largely unable to establish seedlings in the absence of externally supplied sucrose. Measurements of mitochondrial respiration and ATP synthesis revealed that compared with ndufv1, the complex I amounts retained by ndufs4 did not increase mitochondrial respiration and oxidative phosphorylation capacities. No major differences were seen in the mitochondrial proteomes, cellular metabolomes, or transcriptomes between ndufv1 and ndufs4. The analysis of fluxes through the respiratory pathway revealed that in ndufv1, fluxes through glycolysis and the tricarboxylic acid cycle were dramatically increased compared with ndufs4, which showed near wild type-like fluxes. This indicates that the strong growth defects seen for plants lacking complex I originate from a switch in the metabolic mode of mitochondria and an up-regulation of respiratory fluxes. Partial reversion of these phenotypes when traces of active complex I are present suggests that complex I is essential for plant development and likely acts as a negative regulator of respiratory fluxes. PMID- 26134165 TI - Tissue-Specific Apocarotenoid Glycosylation Contributes to Carotenoid Homeostasis in Arabidopsis Leaves. AB - Attaining defined steady-state carotenoid levels requires balancing of the rates governing their synthesis and metabolism. Phytoene formation mediated by phytoene synthase (PSY) is rate limiting in the biosynthesis of carotenoids, whereas carotenoid catabolism involves a multitude of nonenzymatic and enzymatic processes. We investigated carotenoid and apocarotenoid formation in Arabidopsis (Arabidopsis thaliana) in response to enhanced pathway flux upon PSY overexpression. This resulted in a dramatic accumulation of mainly beta-carotene in roots and nongreen calli, whereas carotenoids remained unchanged in leaves. We show that, in chloroplasts, surplus PSY was partially soluble, localized in the stroma and, therefore, inactive, whereas the membrane-bound portion mediated a doubling of phytoene synthesis rates. Increased pathway flux was not compensated by enhanced generation of long-chain apocarotenals but resulted in higher levels of C13 apocarotenoid glycosides (AGs). Using mutant lines deficient in carotenoid cleavage dioxygenases (CCDs), we identified CCD4 as being mainly responsible for the majority of AGs formed. Moreover, changed AG patterns in the carotene hydroxylase mutants lutein deficient1 (lut1) and lut5 exhibiting altered leaf carotenoids allowed us to define specific xanthophyll species as precursors for the apocarotenoid aglycons detected. In contrast to leaves, carotenoid hyperaccumulating roots contained higher levels of beta-carotene-derived apocarotenals, whereas AGs were absent. These contrasting responses are associated with tissue-specific capacities to synthesize xanthophylls, which thus determine the modes of carotenoid accumulation and apocarotenoid formation. PMID- 26134166 TI - Ethylene Regulates the Arabidopsis Microtubule-Associated Protein WAVE-DAMPENED2 LIKE5 in Etiolated Hypocotyl Elongation. AB - The phytohormone ethylene plays crucial roles in the negative regulation of plant etiolated hypocotyl elongation. The microtubule cytoskeleton also participates in hypocotyl cell growth. However, it remains unclear if ethylene signaling-mediated etiolated hypocotyl elongation involves the microtubule cytoskeleton. In this study, we functionally identified the previously uncharacterized microtubule associated protein WAVE-DAMPENED2-LIKE5 (WDL5) as a microtubule-stabilizing protein that plays a positive role in ethylene-regulated etiolated hypocotyl cell elongation in Arabidopsis (Arabidopsis thaliana). ETHYLENE-INSENSITIVE3, a key transcription factor in the ethylene signaling pathway, directly targets and up regulates WDL5. Etiolated hypocotyls from a WDL5 loss-of-function mutant (wdl5-1) were more insensitive to 1-aminocyclopropane-1-carboxylic acid treatment than the wild type. Decreasing WDL5 expression partially rescued the shorter etiolated hypocotyl phenotype in the ethylene overproduction mutant eto1-1. Reorganization of cortical microtubules in etiolated hypocotyl cells from the wdl5-1 mutant was less sensitive to 1-aminocyclopropane-1-carboxylic acid treatment. These findings indicate that WDL5 is an important participant in ethylene signaling inhibition of etiolated hypocotyl growth. This study reveals a mechanism involved in the ethylene regulation of microtubules through WDL5 to inhibit etiolated hypocotyl cell elongation. PMID- 26134168 TI - Watts Towers. Sam Rodia as a contemporary artist. PMID- 26134167 TI - Plastidial Glycolytic Glyceraldehyde-3-Phosphate Dehydrogenase Is an Important Determinant in the Carbon and Nitrogen Metabolism of Heterotrophic Cells in Arabidopsis. AB - This study functionally characterizes the Arabidopsis (Arabidopsis thaliana) plastidial glycolytic isoforms of glyceraldehyde-3-phosphate dehydrogenase (GAPCp) in photosynthetic and heterotrophic cells. We expressed the enzyme in gapcp double mutants (gapcp1gapcp2) under the control of photosynthetic (Rubisco small subunit RBCS2B [RBCS]) or heterotrophic (phosphate transporter PHT1.2 [PHT]) cell-specific promoters. Expression of GAPCp1 under the control of RBCS in gapcp1gapcp2 had no significant effect on the metabolite profile or growth in the aerial part (AP). GAPCp1 expression under the control of the PHT promoter clearly affected Arabidopsis development by increasing the number of lateral roots and having a major effect on AP growth and metabolite profile. Our results indicate that GAPCp1 is not functionally important in photosynthetic cells but plays a fundamental role in roots and in heterotrophic cells of the AP. Specifically, GAPCp activity may be required in root meristems and the root cap for normal primary root growth. Transcriptomic and metabolomic analyses indicate that the lack of GAPCp activity affects nitrogen and carbon metabolism as well as mineral nutrition and that glycerate and glutamine are the main metabolites responding to GAPCp activity. Thus, GAPCp could be an important metabolic connector of glycolysis with other pathways, such as the phosphorylated pathway of serine biosynthesis, the ammonium assimilation pathway, or the metabolism of gamma aminobutyrate, which in turn affect plant development. PMID- 26134170 TI - Duplex Ratio Tests as Diagnostic Biomarkers in Malignant Melanoma. AB - Chromosomal instability is a well-described feature of malignant tumors. Melanomas have typical patterns of chromosomal instability compared with benign nevi, which have minimal DNA copy number change. A few malignant melanomas and their benign counterparts, nevi, prove difficult to diagnose on histopathologic analysis alone, which is currently the gold standard. Quantitative PCR-based assays called duplex ratio tests (DRTs) have been developed by our laboratory for application using DNA from FFPE samples of melanomas and nevi. The reproducibility and accuracy of the DRTs were demonstrated and appropriate correction factors for DNA quality calculated for each assay, based on the results of 108 diploid samples. As a panel, seven DRTs were able to differentiate unambiguous cases of melanoma and nevi with a sensitivity of 87% (95% CI, 83% 91%) and a specificity of 88% (95% CI, 84%-92%) in a series of 145 melanomas and 123 nevi. The DRT scores for 20 nonmetastasizing primary melanomas and 20 metastasizing primary melanomas revealed that DRTs had a marginal benefit as prognostic markers. DRTs have early potential to act as molecular biomarkers of melanoma on FFPE specimens pending validation, and DRTs may have applicability as prognostic markers in melanoma or other tumor types if new DRTs to relevant loci are developed. PMID- 26134169 TI - Structural Model of RNA Polymerase II Elongation Complex with Complete Transcription Bubble Reveals NTP Entry Routes. AB - The RNA polymerase II (Pol II) is a eukaryotic enzyme that catalyzes the synthesis of the messenger RNA using a DNA template. Despite numerous biochemical and biophysical studies, it remains elusive whether the "secondary channel" is the only route for NTP to reach the active site of the enzyme or if the "main channel" could be an alternative. On this regard, crystallographic structures of Pol II have been extremely useful to understand the structural basis of transcription, however, the conformation of the unpaired non-template DNA part of the full transcription bubble (TB) is still unknown. Since diffusion routes of the nucleoside triphosphate (NTP) substrate through the main channel might overlap with the TB region, gaining structural information of the full TB is critical for a complete understanding of Pol II transcription process. In this study, we have built a structural model of Pol II with a complete transcription bubble based on multiple sources of existing structural data and used Molecular Dynamics (MD) simulations together with structural analysis to shed light on NTP entry pathways. Interestingly, we found that although both channels have enough space to allow NTP loading, the percentage of MD conformations containing enough space for NTP loading through the secondary channel is twice higher than that of the main channel. Further energetic study based on MD simulations with NTP loaded in the channels has revealed that the diffusion of the NTP through the main channel is greatly disfavored by electrostatic repulsion between the NTP and the highly negatively charged backbones of nucleotides in the non-template DNA strand. Taken together, our results suggest that the secondary channel is the major route for NTP entry during Pol II transcription. PMID- 26134172 TI - Electromagnetic therapy for treating venous leg ulcers. AB - BACKGROUND: Leg ulceration is a common, chronic, recurring condition. The estimated prevalence of leg ulcers in the UK population is 1.5 to 3 per 1000. Venous ulcers (also called stasis or varicose ulcers) comprise 80% to 85% of all leg ulcers. Electromagnetic therapy (EMT) is sometimes used as a treatment to assist the healing of chronic wounds such as venous leg ulcers. OBJECTIVES: To assess the effects of EMT on the healing of venous leg ulcers. SEARCH METHODS: For this fourth update, we searched The Cochrane Wounds Group Specialised Register (searched 30 January 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 12). SELECTION CRITERIA: Randomised controlled trials comparing EMT with sham-EMT or other treatments. DATA COLLECTION AND ANALYSIS: Standard Cochrane Collaboration methods were employed. At least two review authors independently scrutinised search results and obtained full reports of potentially eligible studies for further assessment. We extracted and summarised details of eligible studies using a data extraction sheet, and made attempts to obtain missing data by contacting study authors. A second review author checked data extraction, and we resolved disagreements after discussion between review authors. MAIN RESULTS: Three randomised controlled trials (RCTs) of low or unclear risk of bias, involving 94 people, were included in the original review; subsequent updates have identified no new trials. All the trials compared the use of EMT with sham-EMT. Meta-analysis of these trials was not possible due to heterogeneity. In the two trials that reported healing rates; one small trial (44 participants) reported that significantly more ulcers healed in the EMT group than the sham-EMT group however this result was not robust to different assumptions about the outcomes of participants who were lost to follow up. The second trial that reported numbers of ulcers healed found no significant difference in healing. The third trial was also small (31 participants) and reported significantly greater reductions in ulcer size in the EMT group however this result may have been influenced by differences in the prognostic profiles of the treatment groups. AUTHORS' CONCLUSIONS: It is not clear whether electromagnetic therapy influences the rate of healing of venous leg ulcers. Further research would be needed to answer this question. PMID- 26134171 TI - Voice Relative Fundamental Frequency Via Neck-Skin Acceleration in Individuals With Voice Disorders. AB - PURPOSE: This study investigated the use of neck-skin acceleration for relative fundamental frequency (RFF) analysis. METHOD: Forty individuals with voice disorders associated with vocal hyperfunction and 20 age- and sex-matched control participants were recorded with a subglottal neck-surface accelerometer and a microphone while producing speech stimuli appropriate for RFF. Rater reliabilities, RFF means, and RFF standard deviations derived from the accelerometer were compared with those derived from the microphone. RESULTS: RFF estimated from the accelerometer had slightly higher intrarater reliability and identical interrater reliability compared with values estimated with the microphone. Although sensor type and the Vocal Cycle * Sensor and Vocal Cycle * Sensor * Group interactions showed significant effects on RFF means, the typical RFF pattern could be derived from either sensor. For both sensors, the RFF of individuals with vocal hyperfunction was lower than that of the controls. Sensor type and its interactions did not have significant effects on RFF standard deviations. CONCLUSIONS: RFF can be reliably estimated using an accelerometer, but these values cannot be compared with those collected via microphone. Future studies are needed to determine the physiological basis of RFF and examine the effect of sensors on RFF in practical voice assessment and monitoring settings. PMID- 26134173 TI - Minimally invasive surgery for endometrial cancer. AB - PURPOSE OF REVIEW: To critically appraise the pertinent literature on traditional laparoscopy and robotically assisted laparoscopy for the treatment of endometrial cancer. RECENT FINDINGS: Multiple retrospective and prospective studies on traditional laparoscopy and retrospective studies on robotically assisted laparoscopy for the treatment of uterine cancers have shown reduced blood loss, shorter length of hospital stay and decreased incidence and severity of postoperative surgical complications compared with laparotomy. Minimally invasive techniques maintain equivalent oncologic results with regard to the number of dissected lymph nodes and overall and disease-free survival rates.Compared with traditional laparoscopy, robotic surgery has a lower rate of conversion to laparotomy, lower blood loss and presents significant ergonomic advantages for the surgeon facilitating execution of complex oncologic procedures. Minimally invasive techniques are particularly advantageous in obese patients, reducing perioperative and postoperative abdominal wound complications. SUMMARY: A thorough review of the literature indicates that minimally invasive approach has a number of established advantages over laparotomy that makes it the surgical treatment option of choice in endometrial carcinoma patients. PMID- 26134175 TI - Self-assembly of amphiphilic Janus dendrimers into mechanically robust supramolecular hydrogels for sustained drug release. AB - Compounds that can gelate aqueous solutions offer an intriguing toolbox to create functional hydrogel materials for biomedical applications. Amphiphilic Janus dendrimers with low molecular weights can readily form self-assembled fibers at very low mass proportion (0.2 wt %) to create supramolecular hydrogels (G'?G'') with outstanding mechanical properties and storage modulus of G'>1000 Pa. The G' value and gel melting temperature can be tuned by modulating the position or number of hydrophobic alkyl chains in the dendrimer structure; thus enabling exquisite control over the mesoscale material properties in these molecular assemblies. The gels are formed within seconds by simple injection of ethanol solvated dendrimers into an aqueous solution. Cryogenic TEM, small-angle X-ray scattering, and SEM were used to confirm the fibrous structure morphology of the gels. Furthermore, the gels can be efficiently loaded with different bioactive cargo, such as active enzymes, peptides, or small-molecule drugs, to be used for sustained release in drug delivery. PMID- 26134176 TI - Insertion and Management of Temporary Pacemakers. AB - Temporary pacemakers are used in a variety of critical care settings. These life saving devices are reviewed in 2 major categories in this review: first, the insertion and management of epicardial pacemakers after and during cardiac surgery; and second, the insertion of transvenous temporary pacemakers for the emergent treatment of bradyarrhythmias. Temporary epicardial pacemakers are used routinely in patients recovering from cardiac surgery. Borrowing from advances in cardiac resynchronization therapy there are many theoretical and untested benefits to pacing the postoperative cardiac surgery patient. Temporary transvenous pacing is traditionally an emergency procedure to stabilize patients suffering from hemodynamically unstable bradyarrhythmia. We review the traditional and expanding use of transvenous pacemakers inside and outside the operating room. PMID- 26134177 TI - The Post-Anesthetic Care of Pediatric Patients With Pulmonary Hypertension. AB - Few conditions make even the most experienced pediatric anesthesiologists take pause. Pulmonary hypertension is one such condition due to the associated high perioperative morbidity and mortality. Much is written about the intraoperative management of pediatric pulmonary hypertension. This article will instead focus on postoperative care and review the evidence in support of a risk stratification approach for the post-anesthetic disposition of these patients. The total risk for post-anesthetic adverse events includes the patient's baseline risk factors and the incremental risks imposed by the procedure and anesthetic. A proposal with recommendations to guide practitioners and a table summarizing relevant factors are provided. Last, the readers' attention is drawn to the heterogeneity of pulmonary hypertensive disease. Pulmonary arterial hypertension (precapillary) differs significantly from pulmonary venous hypertension (postcapillary); the anesthetic management for one may be relatively contraindicated in the other. Their dissimilarities justify the need to distinguish them for study and research endeavors. PMID- 26134179 TI - Poly (I:C) downregulates platelet production and function through type I interferon. AB - Thrombocytopenia is a frequent complication of viral infections; the underlying mechanisms appear to depend on the identity of the virus involved. Previous research, including reports from our group, indicates that as well as having antiviral activity type I interferons (IFN I) selectively downregulate platelet production. In this study we extended understanding of the role of endogenous IFN I in megakaryo/thrombopoiesis by evaluating platelet and megakaryocyte physiology in mice treated with polyinosinic:polycytidylic acid [poly (I:C)], a synthetic analogue of double-stranded RNA, Toll-like receptor-3 ligand and strong IFNbeta inducer. Mice-treated with poly (I:C) showed thrombocytopaenia, an increase in mean platelet volume and abnormal haemostatic and inflammatory platelet-mediated functionality, indicated by decreased fibrinogen binding and platelet adhesion, prolonged tail bleeding times and impaired P-Selectin externalisation, RANTES release and thrombin-induced platelet-neutrophil aggregate formation. These changes were associated with an increase in size and an abnormal distribution of bone marrow megakaryocytes within the vascular niche and were directly correlated with the plasmatic and bone marrow IFNbeta levels. All these effects were absent in genetically modified mice lacking the IFN I receptor. Our results suggest that IFN I is the central mediator of poly (I:C)-induced thrombocytopenia and platelet dysfunction and indicate that these abnormalities are due to changes in the last stages of megakaryocyte development. These data provide new evidence for the role of IFN I in megakaryocyte distribution in the bone marrow niches and its influence on thrombopoiesis and haemostasis. PMID- 26134180 TI - On-the-Fly Kinetic Monte Carlo Simulation of Aqueous Phase Advanced Oxidation Processes. AB - We have developed an on-the-fly kinetic Monte Carlo (KMC) model to predict the degradation mechanisms and fates of intermediates and byproducts that are produced during aqueous-phase advanced oxidation processes (AOPs). The on-the-fly KMC model is composed of a reaction pathway generator, a reaction rate constant estimator, a mechanistic reduction module, and a KMC solver. The novelty of this work is that we develop the pathway as we march forward in time rather than developing the pathway before we use the KMC method to solve the equations. As a result, we have fewer reactions to consider, and we have greater computational efficiency. We have verified this on-the-fly KMC model for the degradation of polyacrylamide (PAM) using UV light and titanium dioxide (i.e., UV/TiO2). Using the on-the-fly KMC model, we were able to predict the time-dependent profiles of the average molecular weight for PAM. The model provided detailed and quantitative insights into the time evolution of the molecular weight distribution and reaction mechanism. We also verified our on-the-fly KMC model for the destruction of (1) acetone, (2) trichloroethylene (TCE), and (3) polyethylene glycol (PEG) for the ultraviolet light and hydrogen peroxide AOP. We demonstrated that the on-the-fly KMC model can achieve the same accuracy as the computer-based first-principles KMC (CF-KMC) model, which has already been validated in our earlier work. The on-the-fly KMC is particularly suitable for molecules with large molecular weights (e.g., polymers) because the degradation mechanisms for large molecules can result in hundreds of thousands to even millions of reactions. The ordinary differential equations (ODEs) that describe the degradation pathways cannot be solved using traditional numerical methods, but the KMC can solve these equations. PMID- 26134178 TI - Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors. AB - Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. PMID- 26134181 TI - Allergic rhinitis and voice change. AB - The aim of this study was to investigate voice function in patients with birch pollen allergy. Voice recordings for acoustic analysis were performed during pollen season and non-pollen season, with 30 patients and 30 controls, and all participants answered a questionnaire about voice symptoms. The results show that the patients reported more voice symptoms than controls during both seasons. In the non-pollen season the symptoms were decreased in the patient group but not in the controls. Speaking fundamental frequency was lower in patients compared to controls during both seasons. The results suggest chronic edema of the vocal folds in the patients. Laryngeal examination with stroboscope was not performed but is recommended for future patients diagnosed with an air-borne allergy. PMID- 26134182 TI - Is testing the voice under sedation reliable in medialization thyroplasty? AB - OBJECTIVES: Medialization thyroplasty is an accepted method for improving non compensated unilateral vocal cord palsy. Most surgeons decide the depth of penetration of the prosthesis by monitoring the voice changes in the patient during the surgical procedure. General anesthesia with intubation is incompatible with this procedure. Sedation is recommended. In this study we want to objectivize and quantify the influence of sedation and position on voice in order to know if this anesthetic procedure is justified in medialization thyroplasties. STUDY DESIGN: A prospective study. METHODS: This study involved 15 adult patients who underwent sedation. Voice recordings were performed in each patient in three different positions and conditions: the seated position without sedation, the supine position without sedation, and the supine position under the effects of sedation. The sedation drugs used were midazolam, fentanyl, and propofol. The level of sedation was monitored using the observational scale and the bispectral index. RESULTS: The acoustic data obtained from sustained vowel sounds from patient recordings showed that sedation significantly affected the values of pitch. Compared to recordings from patients without sedation, pitch values in patients under sedation were significantly higher for jitter local and shimmer local recordings and significantly lower for pitch and harmonics-to-noise ratio. The supine position was shown not to influence on the voice. CONCLUSIONS: Sedation exerts an important influence on voice quality. General anesthesia could be an alternative, focusing our attention on monitoring the glottis with a fibrolaryngoscope during the surgical procedure. No sedation at all can also be an alternative. PMID- 26134183 TI - Integrating Microarray Data and GRNs. AB - With the completion of the Human Genome Project and the emergence of high throughput technologies, a vast amount of molecular and biological data are being produced. Two of the most important and significant data sources come from microarray gene-expression experiments and respective databanks (e,g., Gene Expression Omnibus-GEO (http://www.ncbi.nlm.nih.gov/geo)), and from molecular pathways and Gene Regulatory Networks (GRNs) stored and curated in public (e.g., Kyoto Encyclopedia of Genes and Genomes-KEGG (http://www.genome.jp/kegg/pathway.html), Reactome (http://www.reactome.org/ReactomeGWT/entrypoint.html)) as well as in commercial repositories (e.g., Ingenuity IPA (http://www.ingenuity.com/products/ipa)). The association of these two sources aims to give new insight in disease understanding and reveal new molecular targets in the treatment of specific phenotypes.Three major research lines and respective efforts that try to utilize and combine data from both of these sources could be identified, namely: (1) de novo reconstruction of GRNs, (2) identification of Gene-signatures, and (3) identification of differentially expressed GRN functional paths (i.e., sub-GRN paths that distinguish between different phenotypes). In this chapter, we give an overview of the existing methods that support the different types of gene expression and GRN integration with a focus on methodologies that aim to identify phenotype-discriminant GRNs or subnetworks, and we also present our methodology. PMID- 26134184 TI - PIVKA-II is an independent prognostic factor for overall survival of HCC patients and maybe associated with epithelial-mesenchymal transition. PMID- 26134185 TI - Safety, complications and outcome of large volume paracentesis with or without albumin therapy in children with severe ascites due to liver disease. AB - BACKGROUND & AIMS: There are currently no published data on post-paracentesis circulatory dysfunction (PPCD) or its prevention in children. Our study was aimed to analyze the safety and complications of large volume paracentesis (LVP) in children with severe ascites due to chronic liver disease with or without albumin therapy. METHODS: A prospective longitudinal observational study enrolled children with severe ascites who underwent single time LVP at admission. They were divided into albumin infused (AI) and albumin non-infused (ANI) groups. Hemodynamic monitoring and laboratory parameters including plasma renin activity (PRA) were compared between baseline, 48 h and day 6 of LVP. Their outcome at 3 months and maximal follow-up were noted. RESULTS: 32 children (AI, n=17; ANI, n=15) had comparable baseline characteristics and 90.6% had high PRA at onset. The incidence of PPCD was 37.5% (ANI: 67%; AI: 12%, p=0.003), occurred if ascitic fluid extraction was >197.5 ml/kg (sensitivity: 90%; specificity: 50%, p=0.01) and if flow rate was higher in ANI group (1224 +/- 476 vs. 678 +/- 214 ml/h, p=0.009). ANI patients were susceptible to asymptomatic, persistent hyponatremia (baseline vs. day 6, 131 +/- 4 vs. 128 +/- 6 mEq/L; p=0.04) and had higher rates of recurrent ascites (42%) and hospital readmission (67%) within 3 months. No survival benefit among the AI or non-PPCD groups was demonstrated. CONCLUSIONS: LVP is safe in all age groups, best performed under albumin cover to overcome the problems of PPCD and hyponatremia. It is prudent to restrict volume extraction to less than 200 ml/kg actual dry weight for all and flow rate of 680 ml/h in ANI. PMID- 26134186 TI - Foods, Drugs and Environmental Factors: Novel Kounis Syndrome Offenders. AB - Kounis syndrome is hypersensitivity coronary disorder induced by various types of environmental exposures, drugs, conditions and stents. Allergic, hypersensitivity, anaphylactic and anaphylactoid reactions are associated with this syndrome. The disorder manifests as coronary spasms, acute myocardial infarction and stent thrombosis and affects the cerebral and mesenteric as well as coronary arteries. Importantly, its manifestations are broad and its etiology is continuously increasing. Recently, a variety of unusual etiologies have been reported including Anisakis simplex, scombroid syndrome, the use of Gelofusin or ultrasound contrast agents, kiwifruit, fly bites, and bee stings. Furthermore, losartan and the paradox of corticosteroid allergy have been implicated as possible causes. Although not rare, Kounis syndrome is infrequently diagnosed. Therefore, awareness of its etiology, manifestations and pathophysiology is important for providing the proper diagnosis and treatment and determining prognosis. PMID- 26134187 TI - Effects of Add-on Therapy Consisting of a Selective Mineralocorticoid Receptor Blocker on Arterial Stiffness in Patients with Uncontrolled Hypertension. AB - OBJECTIVE: Aldosterone plays an important role in the pathogenesis of atherosclerosis; however, the significance of mineralocorticoid receptor blockade for atherosclerosis has not been fully elucidated. In this study, the effect of add-on eplerenone on the degree of arterial stiffness was examined in patients with uncontrolled hypertension. METHODS: Forty-seven uncontrolled hypertensive patients who had previously been treated with anti-hypertensive drugs were examined retrospectively. Thirty-two patients received add-on therapy consisting of eplerenone (Group E) and 15 patients received add-on therapy with a Calcium channel blocker (CCB) or an increased dose of CCB (Group C) in addition to their baseline medications. Both the systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were significantly decreased at two and 12 months in Group C. In contrast, neither the SBP nor DBP values were significantly changed at two months and eventually decreased at 12 months in Group E. The degree of arterial stiffness, as evaluated according to the cardio-ankle vascular index (CAVI), did not improve at either two or 12 months in Group C, whereas the CAVI values improved as early as at two months and the improvement was sustained at 12 months in Group E. The extent of change in the CAVI was not associated with the level of changes in the SBP or DBP values in Group E. CONCLUSION: Treatment with eplerenone added to the patient's baseline medications improves the degree of arterial stiffness as early as at two months after the beginning of treatment, independent of the blood pressure-lowering actions of these drugs in patients with uncontrolled hypertension. PMID- 26134188 TI - An Open-label Longitudinal Study on the Efficacy of Switching from Insulin Glargine or Detemir to Degludec in Type 2 Diabetes Mellitus. AB - OBJECTIVE: Insulin degludec (IDeg), a new long-acting basal insulin, and FlexTouch, a new injection device, recently became available in Japan. The efficacy and usefulness of IDeg and FlexTouch, compared with insulin glargine or detemir, were assessed in patients with type 2 diabetes mellitus. METHODS: We performed an open-label longitudinal trial in 20 patients. After informed consent was obtained, all subjects recorded their self-monitoring data of the blood glucose (BG) level; thereafter, basal insulin was replaced by an IDeg-prefilled FlexTouch with the same dose and duration of time (2 weeks). After using FlexTouch, the patients were provided a device-specific questionnaire. RESULTS: The patients were divided into two groups according to the dose of basal insulin (>=10 U and <10 U). Although the mean fasting BG levels were unchanged, the mean BG levels before basal insulin injection and its standard deviation were significantly reduced after switching to IDeg in the patients receiving a higher dose of basal insulin (mean BG before basal insulin injection: 164 to 144 mg/dL, p=0.002; mean standard deviation: 32 to 22, p=0.031); however, this difference was not observed in the patients receiving a lower dose. The patients with a shorter duration of diabetes and a single injection of insulin preferred FlexTouch compared with conventional insulin devices. CONCLUSION: Replacing basal insulin with IDeg is useful for the stable and accurate control of blood glucose levels in type 2 diabetes for those receiving a higher dose of basal insulin. Furthermore, the patients with a shorter duration of diabetes and a single insulin injection preferred FlexTouch. PMID- 26134189 TI - Incidence of Vitamin D Deficiency and Its Relevance to Bone Metabolism in Japanese Postmenopausal Women with Type 2 Diabetes Mellitus. AB - OBJECTIVE: The aim of this study was to assess the incidence of vitamin D deficiency in Japanese postmenopausal women with type 2 diabetes mellitus. METHODS: Serum 25-hydroxyvitamin D [25(OH)D], intact-parathyroid hormone (PTH), and various bone markers were measured. The primary outcome was the serum level of 25(OH)D. PATIENTS: This study included postmenopausal women with type 2 diabetes mellitus. RESULTS: The study patients included 170 women with a mean 25(OH)D of 20.0 ng/mL. With regard to the serum level of 25(OH)D, the patients were defined as normal (>=30 ng/mL, 8.2% of the patients) and abnormal (<30 ng/mL, 91.8% of the patients, vitamin D deficiency). The latter group was subdivided into severe deficiency (<10 ng/mL, 2.9% of the patients), deficiency (10-19 ng/mL, 47.1% of the patients), and insufficiency (20-29 ng/mL, 41.8% of the patients). There was a significant negative correlation between the serum 25(OH)D level with type I collagen cross-linked N-telopeptides (NTX) and intact PTH, but not between 25(OH)D and the bone quality markers. There was a significant positive correlation between 25(OH)D and the radial bone mineral density, but not between 25(OH)D and the bone mineral density on the lumbar vertebrae and femur. A multivariate analysis identified NTX as the only significant determinant of 25(OH)D. The cutoff value of 25(OH)D was 18.5 ng/mL based on a Receiver Operatorating Characteristic analysis. CONCLUSION: Our results showed an alarmingly high incidence of vitamin D deficiency in Japanese women with type 2 diabetes mellitus, with a risk of radial bone osteoporosis, particularly in those patients with a serum 25(OH)D level of <18.5 ng/mL. PMID- 26134190 TI - Mesalazine-induced Pleuropericarditis in a Patient with Crohn's Disease. AB - A 16-year-old boy was diagnosed with Crohn's disease. Treatment with oral mesalazine was started at 3 g per day; however, he complained of high fever, a nonproductive cough, and left shoulder pain after 2 weeks. His chest radiography and chest computed tomography showed cardiomegaly and left pleural effusion, while an echocardiogram revealed pericardial effusion. Because no infection was detected by thoracentesis and the drug lymphocyte stimulation tests for mesalazine were positive, the patient was diagnosed with mesalazine-induced pleuropericarditis. After the cessation of mesalazine, the clinical symptoms and laboratory findings quickly improved. PMID- 26134191 TI - A Patient with Vigorous Achalasia and Rapid Enlargement of an Epiphrenic Esophageal Diverticulum. AB - A 47-year-old man was found to have a 3-cm epiphrenic esophageal diverticulum on an upper gastrointestinal (UGI) barium study. He developed the symptoms of heartburn approximately 12 months later. UGI endoscopy indicated non-erosive gastroesophageal reflux disease (NERD) and an epiphrenic esophageal diverticulum. A proton pump inhibitor (PPI) did not relieve the symptoms. An UGI barium study at that time showed that the epiphrenic esophageal diverticulum had enlarged to 7 cm, and esophageal manometry showed findings of achalasia and diffuse esophageal spasm (DES), thus vigorous achalasia was diagnosed. Resection of the epiphrenic esophageal diverticulum, myotomy, and fundoplication (the Heller-Dor procedure) were successfully performed and no postoperative symptoms were encountered. PMID- 26134192 TI - Sarcomatoid Hepatocellular Carcinoma with Spontaneous Intraperitoneal Bleeding. AB - An 80-year-old woman was admitted to our hospital with right hypochondralgia. Abdominal ultrasonography showed a well-circumscribed round lesion in segments 5 and 6 of the liver. Contrast-enhanced ultrasonography (CEUS) indicated that the tumor was enhanced in the arterial phase, changing to hypo-enhanced 30 seconds following contrast injection. After admission, the patient complained of epigastralgia, and CEUS subsequently demonstrated extravasation from the tumor. Although abdominal angiography was successful for achieving hemostasis, the tumor grew rapidly and the patient died. An autopsy revealed the presence of sarcomatoid hepatocellular carcinoma (HCC). The literature is lacking in details regarding CEUS findings for sarcomatoid HCC and rupture. We herein report a rare case of sarcomatoid HCC. PMID- 26134193 TI - Portosystemic Encephalopathy without Liver Cirrhosis Masquerading as Depression. AB - A 69-year-old woman was hospitalized due to progressive lethargy with hyperammonemia. Five months before the current admission, she was diagnosed with depression based on her low level of daily physical activity and thus began taking antidepressants. Abdominal computed tomography revealed a portosystemic shunt running between the left renal vein and inferior mesenteric vein. Balloon occluded retrograde transvenous obliteration of the shunt vessel was performed, and the patient showed a remarkable clinical improvement. The possibility of a portosystemic shunt should be considered in the presence or absence of underlying liver disease and the ammonia level should be measured before diagnosing depression, as portosystemic encephalopathy may be reversible with interventional radiology treatment. PMID- 26134194 TI - Two Cases of Liver Abscesses Derived from Dental Disease in Patients with Alcoholic Chronic Pancreatitis. AB - Among the etiologies of pyogenic liver abscess (PLA), bacterial spread from the biliary tract or portal flow is the major cause, while the onset of PLA due to arterial bacterial transmission is rare. We herein report two cases of PLA thought to be caused by arterial transmission from dental disease. In both cases, there was benign biliary stricture as a result of alcoholic chronic pancreatitis, although normal oral flora was detected as the causative bacteria and oral hygiene was poor in both patients. We presumed that the origin of PLA was dental disease and successfully treated the patients with percutaneous drainage, antibiotics and dental procedures. PMID- 26134195 TI - Myocardial Calcification with a Latent Risk of Congestive Heart Failure in a Patient with Apical Hypertrophic Cardiomyopathy. AB - Myocardial calcification is rare. An 88-year-old man who had previously been diagnosed with apical hypertrophic cardiomyopathy exhibited left ventricular asynergy on echocardiography before undergoing cholecystectomy. Computed tomography revealed severe calcification in the apical region of the left ventricular myocardium, although the coronary arteries were intact and the hemodynamics on right heart catheterization were normal. The cause of the left ventricular asynergy appeared to be myocardial calcification, thought to be the result of rheumatic fever based on the patient's past history. Stress echocardiography showed a latent risk for the development of heart failure due to the distensibility of the calcified left ventricular myocardium. PMID- 26134196 TI - Thyroid Storm with Heart Failure Treated with a Short-acting Beta-adrenoreceptor Blocker, Landiolol Hydrochloride. AB - Beta-adrenoreceptor blockers are essential in controlling the peripheral actions of thyroid hormones and a rapid heart rate in patients with thyroid storm, although they should be used with great caution when there is the potential for heart failure. A 67-year-old woman was diagnosed as having thyroid storm in addition to marked tachycardia with atrial fibrillation and heart failure associated with a reduced left ventricular function. The administration of an oral beta blocker, bisoprolol fumarate, induced hypotension and was not tolerable for the patient, whereas landiolol hydrochloride, a short-acting intravenous beta adrenoreceptor blocker with high cardioselectivity and a short elimination half life, was useful for controlling the patient's tachycardia and heart failure without causing hemodynamic deterioration. PMID- 26134197 TI - Identifying the Cause of the "Saturation Gap": Two Cases of Dapsone-induced Methemoglobinemia. AB - Diaphenylsulfone (DDS: Dapsone) is used for Pneumocystis pneumonia (PCP) prophylaxis, and methemoglobinemia has rarely been reported as a side effect of DDS. We herein report two cases of DDS-related methemoglobinemia in an 81-year old man with organizing pneumonia and an 84-year-old woman with eosinophilic pneumonia under treatment with prednisolone. Both patients initially received trimethoprim/sulfamethoxazole for PCP prophylaxis and were switched to DDS due to side effects and subsequently exhibited a clinically unexplainable decrease in SpO2. Methemoglobinemia was diagnosed based on the findings of arterial blood gas analyses. In both cases, the methemoglobinemia improved after discontinuing DDS. PMID- 26134198 TI - Pulmonary Langerhans Cell Histiocytosis in an Adult Diagnosed with Solitary Inguinal Lymphadenopathy. AB - We herein report an extremely rare case of pulmonary Langerhans cell histiocytosis with a solitary enlarged inguinal lymph node. A 19-year-old man presented with a non-productive cough lasting for over a five-month period and an enlarged left inguinal lymph node that had persisted for four months. A histopathological study of the lymph node specimens found Langerhans cells coupled with eosinophils. Positive immunohistochemical staining for langerin, Cluster of Differentiation 1a, S100 in the Langerhans cells confirmed the diagnosis, and a mildly impaired ventilation function in addition to multiple peripheral pulmonary cystic lesions were detected. The patient was managed with prednisone (0.5 mg/kg daily), with slow tapering over several months. PMID- 26134199 TI - Immune-mediated Neuropathy with Anti-disialosyl IgM Antibodies in Diffuse Large B cell Lymphoma: A Case Report and Literature Review. AB - A 36-year-old man with diffuse large B-cell lymphoma presented with polyneuropathy, and the diagnostic work-up revealed the presence of IgM antibodies against gangliosides with disialosyl residues (GD1b, GD3). He was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone and received high-dose intravenous immunoglobulin for the treatment of neuropathy. After initiating the treatments, the patient's neurological impairment improved dramatically. He currently remains in complete remission without a flare-up of the polyneuropathy. Based upon our experience and other case reports of lymphoma with immune-mediated neuropathy caused by anti disialosyl ganglioside IgM antibodies, we conclude that determining the anti ganglioside antibody profile and beginning early treatment should be considered promptly for patients with malignant lymphoma who develop polyneuropathy. PMID- 26134200 TI - RS3PE Syndrome with Iliopsoas Bursitis Distinguished from an Iliopsoas Abscess Using a CT-guided Puncture. AB - A 55-year-old man was diagnosed with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Contrast-enhanced computed tomography for cancer screening showed a mass with low-density centers with an enhanced rim in the left iliopsoas muscle. We suspected an iliopsoas abscess and performed computed-tomography-guided puncture of the mass. Both Gram staining and the culture of the fluid were negative. We diagnosed the patient with RS3PE syndrome with iliopsoas bursitis and administered low-dose corticosteroids without antibiotics. The symptoms, including left hip pain, quickly disappeared following treatment. Clinicians should be aware that iliopsoas bursitis may resemble an iliopsoas abscess. As a result, it is important to make an accurate differential diagnosis. PMID- 26134201 TI - A Patient with Dengue Fever Presenting with Rhabdomyolysis. AB - A 16-year-old boy stayed in Tokyo near Yoyogi Park for extracurricular high school activities. After returning home, he experienced an episode of fever and visited our emergency outpatient unit. He initially exhibited symptoms of leukopenia, thrombocytopenia and concomitant rhabdomyolysis and after admission simultaneously developed a biphasic fever and systemic erythema. Based on the results of reverse transcription polymerase chain reaction testing, he was finally diagnosed with dengue fever. After an absence of 70 years, dengue fever has reemerged as a domestic infection. Awareness of this trend led to our diagnosis. PMID- 26134202 TI - Severe Sepsis due to Otogenic Pneumococcal Meningitis with Pneumocephalus without Meningeal Symptoms. AB - The absence of meningeal signs and symptoms is rare in patients with bacterial meningitis and may lead to a delay in diagnosis and treatment. Furthermore, the onset of bacterial meningitis associated with pneumocephalus is a rare complication of ear infections. We herein report a rare case of otogenic meningitis complicated by pneumocephalus that was initially missed due to the absence of typical meningeal signs and symptoms and later diagnosed correctly based on a thorough review of the patient's systems. PMID- 26134203 TI - Cytomegalovirus-induced Duodenal Papillitis. PMID- 26134204 TI - Emphysematous Gastritis in a Patient with Breast Cancer. PMID- 26134205 TI - Post-stenotic Helical Aortic Flow on 4D-flow MRI. PMID- 26134206 TI - Giant Left Atrial Appendage Mimicking a Mediastinal Tumor. PMID- 26134207 TI - A Rare Form of Intra-isthmus Reentry. PMID- 26134208 TI - Relapsing Polychondritis Followed Up with FDG-PET. PMID- 26134209 TI - Colon Involvement in Blastic Plasmacytoid Dendritic Cell Neoplasm. PMID- 26134211 TI - An Unusual Cause of Hematuria: Emphysematous Cystitis. PMID- 26134210 TI - An Uncommon Diagnostic Algorithm for a Common Condition. PMID- 26134212 TI - Erratum for Renal and Vascular Protective Effects of Ezetimibe in Chronic Kidney Disease. PMID- 26134214 TI - Appropriateness of Parenteral Nutrition Usage in Cancer Patients. AB - This study is to investigate the indication appropriateness of parenteral nutrition (PN) administration in cancer patients. Between December 2013 and August 2014, all cancer patients who received PN (including total PN and Kabiven) in a regional hospital of Southern Taiwan were included in this retrospective study. A total of 107 cancer patients received PN. Among them, colorectal cancer was the most common type of cancer (n = 45, 42.1%), followed by gastric cancer, head and neck cancer, and esophageal cancer. After evaluation of the appropriateness of PN administration, 88 (82.2%) PN episodes were considered appropriate and unavoidable, 4 (3.7%) as appropriate and avoidable but 15 (14.1%) as inappropriate. In conclusion, PN could be inappropriately used by some oncologic physicians. Physicians and nutrition support team specialists should carefully evaluate the indication of PN administration for cancer patients to obey the generally acknowledged usage rule. PMID- 26134213 TI - [Hip replacement in patients with neuromuscular disorders]. AB - BACKGROUND: Primary total hip replacement in patients with neuromuscular disorders is a challenge for the surgeon and the perioperative team. OBJECTIVES: Special considerations have to be given to implant selection as well as surgical approach and surgical technique. METHODS: The paper presents the current literature on total hip replacements in patients with neuromuscular disorders and the authors' personal experience. RESULTS: Interdisciplinary perioperative management, special knowledge of the anatomic and neuromuscular pathology in patients with neuromuscular disorders, as well as detailed preoperative planning are essential to avoid complications. The choice of the surgical approach should be based on the underlying neuromuscular pathology (spastic vs. paralytic) as well as the need to extend the surgery (soft tissue balancing, femoral shortening osteotomy, acetabular reconstruction). In addition to standard implants special acetabular components might be required for patients with an increased risk of postoperative dislocation, and modular femoral components are indicated for patients with excessive femoral anteversion. CONCLUSIONS: Total hip replacement is a successful treatment option for patients with neuromuscular disorders. While most patients will experience pain relief, functional improvements often depend on the underlying neuromuscular disorder and the preoperative function level. The treatment is complex and requires a specialized team to optimize the outcome of the surgery. PMID- 26134215 TI - Evaluation of semi-quantitative method for quantification of dopamine transporter in human PET study with 18F-FE-PE2I. AB - OBJECTIVES: Positron emission tomography (PET) with 18F-FE-PE2I is useful for investigating the function of dopamine transporter, and kinetics of 18F-FE-PE2I could be described by standard two-tissue compartment model (2CM) using plasma input function. In this study, we investigated the feasibility of semi quantitative methods for estimating binding potential (BPND) and transporter occupancy to shorten the scan period and to reduce the effect of statistical noise on quantitative outcomes using computer simulation and human PET studies with 18F-FE-PE2I. METHODS: In the simulations, time-activity curves (TACs) for the putamen with a wide range of BPND were generated. In these TACs, BPNDs were estimated by standardized uptake value ratio (SUVR) using various integration intervals and the simplified reference tissue model (SRTM) with the cerebellum as reference region, and reduction of BPND assuming transporter occupancy by antipsychotics was calculated from BPND obtained from TACs with various BPND values. These estimates were evaluated by comparison with those of 2CM. In human studies with normal volunteers, BPNDs were estimated in the caudate and putamen using SUVR and SRTM with the cerebellar reference region, and compared with BPND by standard 2CM. RESULTS: In the simulations, BPND estimated by SUVR with late time frames and SRTM showed linear correlation with those by 2CM, although the estimates by SUVR were overestimated and affected by the cerebral blood flow as BPND became higher. As for transporter occupancy, SRTM showed higher linearity with 2CM and less effect of statistical noise than the SUVR method. In human studies, BPND by SRTM and SUVR with late time frames showed good correlation with BPND by 2CM. CONCLUSIONS: Although SRTM is more reliable than the SUVR method for BPND and occupancy estimation, SUVR using late time frames has the potential to provide practical indices of BPND and occupancy with a shorter scan period. PMID- 26134216 TI - Application of the newly developed Japanese adenosine normal database for adenosine stress myocardial scintigraphy. AB - OBJECTIVES: The currently available Japanese normal database (NDB) in stress myocardial perfusion scintigraphy recommended by the Japanese Society of Nuclear Medicine (JSNM-NDB) is created based on the data from exercise tests. The newly developed adenosine normal database (ADS-NDB) remains to be validated for patients undergoing adenosine stress test. We tested whether the diagnostic accuracy of adenosine stress test is improved by the use of ADS-NDB (Kanazawa University). METHODS: Of 233 consecutive patients undergoing (99m)Tc-MIBI adenosine stress test, 112 patients were tested. The stress/rest myocardial (99m)Tc-MIBI single-photon emission computed tomography (SPECT) images were analyzed by AutoQUANT 7.2 with both ADS-NDB and JSNM-NDB. The summed stress score (SSS) and summed difference score (SDS) were calculated. The agreements of the post-stress defect severity between ADS-NDB and JSNM-NDB were assessed using a weighted kappa statistic. RESULTS: In all patients, mean SSSs of all, right coronary artery (RCA), left anterior descending (LAD), and left circumflex (LCx) territories were significantly lower with ADS-NDB than those with JSNM-NDB. Mean SDSs in all, RCA, and LAD territories were significantly lower with ADS-NDB than those with JSNM-NDB. In 28 patients with significant coronary stenosis, the mean SSS in the RCA territory was significantly lower with ADS-NDB than that with JSNM NDB. In 84 patients without ischemia, both mean SSSs and SDSs in all, RCA, LAD, and LCx territories were significantly lower with ADS-NDB than those with JSNM NDB. Weighted kappa values of all patients, patients with significant stenosis, and patients without ischemia were 0.89, 0.83, and 0.92, respectively. CONCLUSIONS: Differences were observed between results from ADS-NDB and JSNM-NDB. The diagnostic accuracy of adenosine stress myocardial perfusion scintigraphy may be improved by reducing false-positive results. PMID- 26134217 TI - Effect of cooperativity in lithium bonding on the strength of halogen bonding and tetrel bonding: (LiCN)n...ClYF3 and (LiCN)n...YF3Cl (Y = C, Si and n = 1-5) complexes as a working model. AB - This paper reports results of cooperativity in lithium bonding on the strength of halogen bonding and tetrel bonding in complexes pairing CF3Cl and SiF3Cl with (LiCN)n complexes, where n varies from 1 to 5. Molecular geometries and stabilization energies of title complexes are calculated at the MP2 level with 6 311++G(d,p) basis set. Cooperative effects are found in terms of structural and energetic properties when lithium, halogen, and tetrel bonds are present in these complexes simultaneously. Our results reveal that strength of halogen and tetrel bondings are enhanced due to cooperativity of Li...N interactions in lithium bonded complexes. Good linear correlations between cooperativity parameters and electronic properties of complexes were established in the present study. PMID- 26134219 TI - Non-Small-Cell Lung Cancer: Role of the Immune System and Potential for Immunotherapy. AB - As the leading cause of cancer death worldwide, lung cancer continues to impose a major burden on healthcare systems and cause significant challenges for clinicians and patients. Most patients present with advanced disease at the time of diagnosis and have a poor prognosis, with the vast majority surviving less than 5 years. Although new therapies have been introduced in recent years that target molecular disease drivers present in a subset of patients, there is a significant need for treatments able to improve response and extend survival while minimizing effects on quality of life. Recent evidence of clinical efficacy for immunotherapeutic approaches for lung cancer suggests that they will become the next major therapeutic advance for this disease. Non-small-cell lung cancer, which accounts for approximately 85% of lung cancer cases, has historically been considered a nonimmunogenic disease; however, as with several other malignancies, recent data show that much of this lack of immune responsiveness is functional rather than structural (i.e., possible to overcome therapeutically). This review explores the key elements of the immune system involved in non-small-cell lung cancer and briefly examines immunotherapeutic strategies in development to shift the balance of immune activity away from a tumor-induced immune-suppressive state toward an active antitumor immune response. PMID- 26134220 TI - Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer: In what state is this art? AB - Therapeutic antibodies to programmed death receptor 1 (PD-1) and its ligand PD-L1 show promising clinical results. Anti-PD-L1 immunohistochemistry (IHC) may be a biomarker to select patients more likely to respond to these treatments. However, the development of at least four different therapeutics, each with a different anti-PD-L1 IHC assay, has raised concerns among pathologists and oncologists alike. This article reviews existing data on the IHC biomarker aspects of studies using these drugs in non-small-cell lung cancer (NSCLC) and considers the challenges ahead, should these drug/IHC assay combinations reach routine practice. For each the known biomarker assays in development, there is a different monoclonal IHC antibody clone, produced by one of two diagnostics companies. Each test requires proprietary staining platforms and uses different definitions of a "positive" test for PD-L1 expression, on tumor cells and, in one test, also on tumor infiltrating immune cells. There are still considerable gaps in our knowledge of the technical aspects of these tests, and of the biological implications and associations of PD-L1 expression in NSCLC, considering heterogeneity of expression, dynamic changes in expression, and prognostic implications among other factors. The International Association for the Study of Lung Cancer Pathology Committee raises the prospect of trying not only to harmonize and standardize testing for PD-L1 by IHC, at least at a technical level, but also, ideally, as a predictive marker, to facilitate availability of this test and a promising treatment for patients with NSCLC. PMID- 26134222 TI - Association of PDCD1 and CTLA-4 Gene Expression with Clinicopathological Factors and Survival in Non-Small-Cell Lung Cancer: Results from a Large and Pooled Microarray Database. AB - INTRODUCTION: Immune checkpoint blockade is being investigated in clinical trials and showed great potential in lung cancer. The prognostic roles of and clinicopathological factors associated with immune checkpoint gene expression, CTLA-4 and PDCD1 remain largely undefined, which encodes cytotoxic-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1), respectively. METHODS: We used a lung cancer database of 1715 patients measured by Affymetrix microarrays to analyze the association of gene expression with clinicopathological factors and survival. Hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) were calculated. Cutoffs were determined by median across the entire database. RESULTS: In 909 patients with histology information, significantly higher PDCD1 and CTLA-4 expression were found in squamous carcinoma than adenocarcinoma. In 848 patients with known smoking history, current/former smokers were found to have significantly elevated gene expression compared with nonsmokers. Significant higher expression of both genes were found in TNM stage II versus I. Higher expression of PDCD1 predicted worse OS in univariate analysis, but not in multivariate (HR: 1.22; 95% CI: 0.53-2.79). CTLA-4 was marginally significant in univariate analysis of the entire set (HR: 1.15; 95% CI: 0.99-1.34). In patients with information for multivariate analysis, higher expression of CTLA-4 was associated with worse OS (HR: 1.96; 95% CI: 1.18-3.31). CONCLUSIONS: In this study with large number of patients, PDCD1 and CTLA-4 expression is significantly higher in squamous carcinoma and current/former smokers. Higher expression of CTLA-4, but not PDCD1 predicts worse survival. PMID- 26134221 TI - The IASLC Lung Cancer Staging Project: Proposals for the Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. AB - INTRODUCTION: An international database was collected to inform the 8 edition of the anatomic classification of lung cancer. The present analyses concern its primary tumor (T) component. METHODS: From 1999 to 2010, 77,156 evaluable patients, 70,967 with non-small-cell lung cancer, were collected; and 33,115 had either a clinical or a pathological classification, known tumor size, sufficient T information, and no metastases. Survival was measured from date of diagnosis or surgery for clinically and pathologically staged tumors. Tumor-size cutpoints were evaluated by the running log-rank statistics. T descriptors were evaluated in a multivariate Cox regression analysis adjusted for age, gender, histological type, and geographic region. RESULTS: The 3-cm cutpoint significantly separates T1 from T2. From 1 to 5 cm, each centimeter separates tumors of significantly different prognosis. Prognosis of tumors greater than 5 cm but less than or equal to 7 cm is equivalent to T3, and that of those greater than 7 cm to T4. Bronchial involvement less than 2 cm from carina, but without involving it, and total atelectasis/pneumonitis have a T2 prognosis. Involvement of the diaphragm has a T4 prognosis. Invasion of the mediastinal pleura is a descriptor seldom used. CONCLUSIONS: Recommended changes are as follows: to subclassify T1 into T1a (<=1 cm), T1b (>1 to <=2 cm), and T1c (>2 to <=3 cm); to subclassify T2 into T2a (>3 to <=4 cm) and T2b (>4 to <=5 cm); to reclassify tumors greater than 5 to less than or equal to 7 cm as T3; to reclassify tumors greater than 7 cm as T4; to group involvement of main bronchus as T2 regardless of distance from carina; to group partial and total atelectasis/pneumonitis as T2; to reclassify diaphragm invasion as T4; and to delete mediastinal pleura invasion as a T descriptor. PMID- 26134223 TI - An Integrated Prognostic Classifier for Stage I Lung Adenocarcinoma Based on mRNA, microRNA, and DNA Methylation Biomarkers. AB - INTRODUCTION: Up to 30% stage I lung cancer patients suffer recurrence within 5 years of curative surgery. We sought to improve existing protein-coding gene and microRNA expression prognostic classifiers by incorporating epigenetic biomarkers. METHODS: Genome-wide screening of DNA methylation and pyrosequencing analysis of HOXA9 promoter methylation were performed in two independently collected cohorts of stage I lung adenocarcinoma. The prognostic value of HOXA9 promoter methylation alone and in combination with mRNA and miRNA biomarkers was assessed by Cox regression and Kaplan-Meier survival analysis in both cohorts. RESULTS: Promoters of genes marked by polycomb in embryonic stem cells were methylated de novo in tumors and identified patients with poor prognosis. The HOXA9 locus was methylated de novo in stage I tumors (p < 0.0005). High HOXA9 promoter methylation was associated with worse cancer-specific survival (hazard ratio [HR], 2.6; p = 0.02) and recurrence-free survival (HR, 3.0; p = 0.01), and identified high-risk patients in stratified analysis of stages IA and IB. Four protein-coding gene (XPO1, BRCA1, HIF1alpha, and DLC1), miR-21 expression, and HOXA9 promoter methylation were each independently associated with outcome (HR, 2.8; p = 0.002; HR, 2.3; p = 0.01; and HR, 2.4; p = 0.005, respectively), and when combined, identified high-risk, therapy naive, stage I patients (HR, 10.2; p = 3 * 10). All associations were confirmed in two independently collected cohorts. CONCLUSION: A prognostic classifier comprising three types of genomic and epigenomic data may help guide the postoperative management of stage I lung cancer patients at high risk of recurrence. PMID- 26134225 TI - Surgical Intervention for Non-Small-Cell Lung Cancer Patients with Pleural Carcinomatosis: Results From the Japanese Lung Cancer Registry in 2004. AB - INTRODUCTION: A subset of non-small-cell lung cancer (NSCLC) patients with malignant pleural effusion and/or malignant pleural nodules is now classified as stage IV and is generally considered a contraindication to surgery. However, several reports have demonstrated that the prognosis of patients with pleural carcinomatosis first detected at thoracotomy is relatively favorable. The aim of this study was to describe the results of surgical intervention in NSCLC patients with pleural carcinomatosis in Japan. METHODS: In 2010, the Japanese Joint Committee of Lung Cancer Registry conducted a nationwide registration of lung cancer patients who underwent surgery in 2004. Using this database, we performed a retrospective study focused on pleural carcinomatosis. We examined the clinicopathological features, the current status of therapy, and surgical outcomes in patients with pleural carcinomatosis. RESULTS: Among the 11,420 registered NSCLC patients, 329 (2.9%) patients had pleural carcinomatosis. The median survival time and 5-year survival rate of 313 patients without other metastatic disease were 34.0 months and 29.3%, respectively. Primary tumor resection was performed in 256 (81.8%) patients, and macroscopic complete resection was achieved in 152 (48.6%) patients, with 5-year survival rates of 33.1% and 37.1%, respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status (p < 0.001), best stage nodal status (p = 0.002), and the presence or absence of gross residual tumor (p = 0.013) were independent predictors of survival. CONCLUSION: In our surgical registry for NSCLC, patients with pleural carcinomatosis accounted for 2.9%, and macroscopic complete resection for them was associated with better survival. PMID- 26134224 TI - Functional FLT1 Genetic Variation is a Prognostic Factor for Recurrence in Stage I-III Non-Small-Cell Lung Cancer. AB - BACKGROUND: We propose that single-nucleotide polymorphisms (SNPs) in genes of the vascular endothelial growth factor pathway of angiogenesis will associate with survival in non-small-cell lung cancer (NSCLC) patients. METHODS: Fifty three SNPs in vascular endothelial growth factor-pathway genes were genotyped in 150 European stage I-III NSCLC patients and tested for associations with patient survival. Replication was performed in an independent cohort of 142 European stage I-III patients. Reporter gene assays were used to assess the effects of SNPs on transcriptional activity. RESULTS: In the initial cohort, five SNPs associated (q < 0.05) with relapse-free survival (RFS). The minor alleles of intronic FLT1 SNPs, rs7996030 and rs9582036, associated with reduced RFS (hazard ratio [HR] = 1.67 [95% confidence interval, CI, 1.22-2.29] and HR = 1.51 [95% CI, 1.14-2.01], respectively) and reduced transcriptional activity. The minor alleles of intronic KRAS SNPs, rs12813551 and rs10505980, associated with increased RFS (HR = 0.64 [0.46-0.87] and HR = 0.64 [0.47-0.87], respectively), and the minor allelic variant of rs12813551 also reduced transcriptional activity. Lastly, the minor allele of the intronic KRAS SNP rs10842513 associated with reduced RFS (HR = 1.65 [95% CI, 1.16-2.37]). Analysis of the functional variants suggests they are located in transcriptional enhancer elements. The negative effect of rs9582036 on RFS was confirmed in the replication cohort (HR = 1.69 [0.99-2.89], p = 0.028), and the association was significant in pooled analysis of both cohorts (HR = 1.67 [1.21-2.30], p = 0.0001). CONCLUSIONS: The functional FLT1 variant rs9582036 is a prognostic determinant of recurrence in stage I-III NSCLC. Its predictive value should be tested in the adjuvant setting of stage I-III NSCLC. PMID- 26134226 TI - Proposed Modification of Nodal Staging as an Alternative to the Seventh Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Improves the Prognostic Prediction in the Resected Esophageal Squamous-Cell Carcinoma. AB - INTRODUCTION: The 7th American Joint Committee on Cancer (AJCC) tumor-node metastasis staging system for esophageal cancer defined N classification based on the number of metastatic lymph nodes (LNs). However, this classification might neglect the extent of LNs metastasis. This study aimed to revise N classification based on the extent of LNs metastasis and propose a modification to the current AJCC staging system for better representing the prognostic characteristics of Chinese esophageal squamous-cell carcinoma (ESCC). METHODS: We retrospectively reviewed 1993 ESCC patients who underwent curative resection. The proposed N categories based on the number of LNs metastasis stations were compared with the current staging system by univariate and multivariate Cox regression analyses. Homogeneity, discriminatory ability, and monotonicity of gradients of two staging systems were compared using likelihood ratio chi statistics and Akaike information criterion calculations. RESULTS: The survival differences were not significant for N2 versus N3 category (p = 0.231) and stages IIIB versus IIIC (p = 0.713) based on the 7th AJCC staging system. When the modified staging system was adopted, the survival difference for N2 versus N3 and IIIB versus IIIC could be well discriminated. Statistical analysis showed that the modified staging system had higher likelihood ratio chi scores and smaller Akaike information criterion values than the 7th AJCC staging system, which represented the optimum prognostic stratification. CONCLUSIONS: The modified staging system with the revised N categories based on the number of LNs metastasis stations better predicts the survival of Chinese ESCC population than the 7th AJCC staging system. Further studies are required to confirm this result. PMID- 26134228 TI - VAMP2-NRG1 Fusion Gene is a Novel Oncogenic Driver of Non-Small-Cell Lung Adenocarcinoma. AB - INTRODUCTION: Neuregulin 1 (NRG1) has been discovered as the tail moiety of fusion genes with several distinct partner head genes in lung cancers. These fusion genes activate ERBB2/ERBB3 receptor-mediated cell signaling and thereby function as oncogenic drivers. METHODS: We have carried out whole-transcriptome sequencing of 100 non-small-cell lung carcinoma tumors and isolated a novel fusion gene consisting of vesicle-associated membrane protein 2 (VAMP2) and NRG1. Reverse transcription-polymerase chain reaction and genomic DNA analysis were used to demonstrate interchromosomal translocation. Immunoblotting and soft agar assays were used to examine stimulating activity of the fusion gene through ERBB2/ERBB3 signaling pathway. RESULTS: The most highly expressed splice variant of VAMP2-NRG1 fusion gene was shown to be membrane bound and display EGF-like domain of NRG1 extracellularly. VAMP2-NRG1 promotes anchorage-independent colony formation of H1568 lung adenocarcinoma cells. Ectopic expression of the fusion gene stimulates phosphorylation of ERBB2 and ERBB3 as well as downstream targets, AKT and ERK, confirming activation of the signaling pathway. CONCLUSION: VAMP2 NRG1 is a novel oncogenic fusion gene representing a new addition to the list of NRG1 fusion genes, which together may form an important diagnostic and clinical category of lung adenocarcinoma cases. PMID- 26134227 TI - Multitrial Evaluation of Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Extensive-Stage Small-Cell Lung Cancer. AB - INTRODUCTION: We previously reported that progression-free survival (PFS) may be a candidate surrogate end point for overall survival (OS) in first-line extensive stage small-cell lung cancer (ES-SCLC) using data from three randomized trials (Foster, Cancer 2011). In this validation study (N0424-Alliance), we assessed the patient-level and trial-level surrogacy of PFS using data from seven new first line phase II/III ES-SCLC trials and across all 10 trials as well (seven new, three previous). METHODS: Individual patient data were utilized across the seven new trials (2259 patients) and all 10 trials (2855 patients). Patient-level surrogacy (Kendall's tau) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed through association of the log hazard ratios on OS and PFS across trials, including weighted (by trial size) least squares regression (WLS R2) of Cox model effects and correlation of the copula effects (copula R2). The minimum effect on the surrogate (MES) needed to detect a nonzero treatment effect on OS was also calculated. RESULTS: The median OS and PFS across all 10 trials were 9.8 and 5.9 months, respectively. PFS showed strong surrogacy within the 7 new trials (copula R2 = 0.90 [standard error = 0.27], WLS R2 = 0.83 [95% confidence interval: 0.43, 0.95]; MES = 0.67, and Kendall's tau = 0.58) and across all 10 trials (copula R2 = 0.81 [standard errors = 0.25], WLS R2 = 0.77 [95% confidence interval: 0.47-0.91], MES = 0.70, and Kendall's tau = 0.57). CONCLUSIONS: PFS demonstrated strong surrogacy for OS in first-line ES-SCLC based on this external validation study of individual patient data. PFS is a good alternative end point to OS and should be considered when resource constraints (time or patient) might make it useful or desirable in place of OS. Additional analyses are needed to assess its appropriateness for targeted agents in this disease setting. PMID- 26134229 TI - Dosimetric Consequences of 3D Versus 4D PET/CT for Target Delineation of Lung Stereotactic Radiotherapy. AB - INTRODUCTION: Lung tumor delineation is frequently performed using 3D positron emission tomography (PET)/computed tomography (CT), particularly in the radiotherapy treatment planning position, by generating an internal target volume (ITV) from the slow acquisition PET. We investigate the dosimetric consequences of stereotactic ablative body radiotherapy (SABR) planning on 3D PET/CT in comparison with gated (4D) PET/CT. METHODS: In a prospective clinical trial, patients with lung metastases were prescribed 26 Gy single-fraction SABR to the covering isodose. Contemporaneous 3D PET/CT and 4D PET/CT was performed in the same patient position. An ITV was generated from each data set, with the planning target volume (PTV) being a 5-mm isotropic expansion. Dosimetric parameters from the SABR plan derived using the 3D volumes were evaluated against the same plan applied to 4D volumes. RESULTS: Ten lung targets were evaluated. All 3D plans were successfully optimized to cover 99% of the PTV by the 26 Gy prescription. In all cases, the calculated dose delivered to the 4D target was less than the expected dose to the PTV based on 3D planning. Coverage of the 4D-PTV by the prescription isodose ranged from 74.48% to 98.58% (mean of 90.05%). The minimum dose to the 4D-ITV derived by the 3D treatment plan (mean = 93.11%) was significantly lower than the expected dose to ITV based on 3D PET/CT calculation (mean = 111.28%), p < 0.01. In all but one case, the planned prescription dose did not cover the 4D-PET/CT derived ITV. CONCLUSIONS: Target delineation using 3D PET/CT without additional respiratory compensation techniques results in significant target underdosing in the context of SABR. PMID- 26134230 TI - Cystic Brain Metastases in NSCLC Harboring the EML4-ALK Translocation after Treatment with Crizotinib. PMID- 26134231 TI - A Case of Nontuberculous Mycobacteria Highly Suspected as Lung Cancer Invading the Aortic Arch. PMID- 26134232 TI - A Rare Case of Intrapulmonary Ewing Sarcoma Presenting with Left Atrial Tumor Thrombus. PMID- 26134233 TI - Identification of a Novel ALK G1123S Mutation in a Patient with ALK-rearranged Non-small-cell Lung Cancer Exhibiting Resistance to Ceritinib. PMID- 26134234 TI - Discordant HER2 Exon 20 Mutation Status Determines a Differential Sensitivity to Afatinib. PMID- 26134235 TI - Better Prognostic Models May Result in Improved Patient Selection for Adjuvant Therapies After Complete Resection of Solitary Fibrous Tumors of the Pleura. PMID- 26134236 TI - Reply to "Better Prognostic Models May Result in Improved Patient Selection for Adjuvant Therapies After Complete Resection of Solitary Fibrous Tumors of the Pleura". PMID- 26134237 TI - No Increased Risk for Mesothelioma in Relation to Natural-Occurring Asbestos in Southern Nevada. PMID- 26134238 TI - Reply to "No Increased Risk for Mesothelioma in Relation to Natural-Occurring Asbestos in Southern Nevada". PMID- 26134239 TI - Afatinib for Erlotinib Refractory Brain Metastases in a Patient with EGFR-Mutant Non-Small-Cell Lung Cancer: Can High-Affinity TKI Substitute for High-Dose TKI? PMID- 26134240 TI - Emergence of amae crying in early infancy as a possible social communication tool between infants and mothers. AB - Amae is defined as "wishing to be loved (Scheidlinger (1999). The Journal of the American Academy of Psychoanalysis, 27(1), p. 91)". Amae crying is known as crying of infants when seeking intimate emotional communication with caregivers. The objective of this study was to delineate when and how amae crying emerges in early infancy. Crying episodes of four infants were observed bimonthly, in the natural context of their homes, from birth to 6 months of age, for approximately 60min per session. Crying episodes (total=275) as determined by two coders were analyzed with respect to several behavioral measures. Results indicated that amae crying emerged at the age of 2 months, and consistently accounted for 30-40% of the total crying episodes after the ages of 3 months. Amae crying could be accurately identified when infants were not in acute discomfort and had already got the attention of their mothers. At such times, infants did not shed tears, cried with a fussy voice, and frequently looked at their mothers. Mothers responded to amae crying more promptly than they did to other types of crying behaviors. It is concluded that 3 months of age, when infants probably begin to use crying as a social communication tool is a major turning point for crying behavior from the perspective of its biological and social roles. It is suggested that amae crying might play an important role in strengthening and encouraging mother-infant interactions. PMID- 26134241 TI - Rapid and Nondestructive Identification of Polytypism and Stacking Sequences in Few-Layer Molybdenum Diselenide by Raman Spectroscopy. AB - Various combinations of interlayer shear modes emerge in few-layer molybdenum diselenide grown by chemical vapor deposition depending on the stacking configuration of the sample. Raman measurements may also reveal polytypism and stacking faults, as supported by first principles calculations and high resolution transmission electron microscopy. Thus, Raman spectroscopy is an important tool in probing stacking-dependent properties in few-layer 2D materials. PMID- 26134243 TI - Digging adaptation in insectivorous subterranean eutherians. The enigma of Mesoscalops montanensis unveiled by geometric morphometrics and finite element analysis. AB - The enigmatic Early Miocene fossorial mammal Mesoscalops montanensis shows one of the most modified humeri among terrestrial mammals. It has been suggested, on qualitative considerations, that this species has no extant homologues for humerus kinematics and that, functionally, the closest extant group is represented by Chrysochloridae. We combine here three dimensional geometric morphometrics, finite element analysis and phylogenetic comparative methods to explore the shape and mechanical stress states of Mesoscalops montanensis as well as of extant and extinct Talpidae and Chrysochloridae under realistic digging simulations. Evolutionary convergence analyses reveal that the shape of Mesoscalops montanensis represents a unique morphology in the context of fossorial mammals and that its functional performance, albeit superficially similar to that of extant Chrysochloridae, still represents a nonconvergent optimum for adaptation to digging. PMID- 26134244 TI - Periodically Modulated Size-Dependent Elastic Properties of Armchair Graphene Nanoribbons. AB - First-principles calculations were conducted on armchair graphene nanoribbons (AGNRs) to simulate the elastic behavior of AGNRs with hydrogen-terminated and bare edges. The results show width-dependent elastic properties with a periodicity of three, which depends on the nature of edge. The edge eigenstress and eigendisplacement models are able to predict the width-dependent nominal Young's modulus and Poisson's ratio, while the Clar structure explains the crucial role of edges in the periodically modulated size-dependent elastic properties. PMID- 26134242 TI - Connecting Mitochondria, Metabolism, and Stem Cell Fate. AB - As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases. PMID- 26134245 TI - Association of CLOCK, ARNTL, and NPAS2 gene polymorphisms and seasonal variations in mood and behavior. AB - Seasonal affective disorder (SAD) is a condition of seasonal mood changes characterized by recurrent depression in autumn or winter that spontaneously remits in spring or summer. Evidence has suggested that circadian gene variants contribute to the pathogenesis of SAD. In this study, we investigated polymorphisms in the CLOCK, ARNTL, and NPAS2 genes in relation to seasonal variation in 507 healthy young adults. Seasonal variations were assessed with the Seasonality Pattern Assessment Questionnaire. The prevalence of SAD was 12.0% (winter-type 9.3%, summer-type 2.8%). No significant difference was found between the groups in the genotype distribution of ARNTL rs2278749 and NPAS2 rs2305160. The T allele of CLOCK rs1801260 was significantly more frequent in seasonals (SAD + subsyndromal SAD) compared with non-seasonals (p = 0.020, odds ratio = 1.89, 95% confidence interval = 1.09-3.27). Global seasonality score was significantly different among genotypes of CLOCK rs1801260, but not among genotypes of ARNTL rs2278749 and NPAS2 rs2305160. However, statistical difference was observed in the body weight and appetite subscales among genotypes of ARNTL rs2278749 and in the body weight subscale among genotypes of NPAS2 rs2305160. There was synergistic interaction between CLOCK rs1801260 and ARNTL rs2278749 on seasonality. To our knowledge, this study is the first to reveal an association between the CLOCK gene and seasonal variations in mood and behavior in the Korean population. Although we cannot confirm previous findings of an association between SAD and the ARNTL and NPAS2 genes, these genes may influence seasonal variations through metabolic factors such as body weight and appetite. The interaction of the CLOCK and ARNTL genes contributes to susceptibility for SAD. PMID- 26134247 TI - A new triterpenoid glycoside from the leaves and stems of Duranta repens. AB - A new triterpenoid glycoside (1) was isolated from the methanol extract of the leaves and stems of Duranta repens L. (Verbenaceae) along with 14 known compounds consisting of eight triterpenoids, four iridoids, one phenylethanoid glycoside and one flavonoid. The chemical structure of 1 was determined to be bayogenin 3-O [beta-D-glucopyranoside]-28-O-[alpha-L-rhamnopyranosyl-(1->5)-O-beta-D apiofuranosyl-(1->4)-O-alpha-L-rhamnopyranosyl-(1->2)-O-alpha-L-arabinopyranosyl] ester, based on spectroscopic data. In addition, the inhibitory effects of the isolates on lipoxygenase activity were examined. Among them, acteoside and apigenin resulted in 94 +/- 3.6% and 82 +/- 4.7% inhibition, respectively, at 0.5 mM. PMID- 26134248 TI - Protein structural dynamics revealed by time-resolved X-ray solution scattering. AB - One of the most important questions in biological science is how a protein functions. When a protein performs its function, it undergoes regulated structural transitions. In this regard, to better understand the underlying principle of a protein function, it is desirable to monitor the dynamic evolution of the protein structure in real time. To probe fast and subtle motions of a protein in physiological conditions demands an experimental tool that is not only equipped with superb spatiotemporal resolution but also applicable to samples in solution phase. Time-resolved X-ray solution scattering (TRXSS), discussed in this Account, fits all of those requirements needed for probing the movements of proteins in aqueous solution. The technique utilizes a pump-probe scheme employing an optical pump pulse to initiate photoreactions of proteins and an X ray probe pulse to monitor ensuing structural changes. The technical advances in ultrafast lasers and X-ray sources allow us to achieve superb temporal resolution down to femtoseconds. Because X-rays scatter off all atomic pairs in a protein, an X-ray scattering pattern provides information on the global structure of the protein with subangstrom spatial resolution. Importantly, TRXSS is readily applicable to aqueous solution samples of proteins with the aid of theoretical models and therefore is well suited for investigating structural dynamics of protein transitions in physiological conditions. In this Account, we demonstrate that TRXSS can be used to probe real-time structural dynamics of proteins in solution ranging from subtle helix movement to global conformational change. Specifically, we discuss the photoreactions of photoactive yellow protein (PYP) and homodimeric hemoglobin (HbI). For PYP, we revealed the kinetics of structural transitions among four transient intermediates comprising a photocycle and, by applying structural analysis based on ab initio shape reconstruction, showed that the signaling of PYP involves the protrusion of the N-terminus with significant increase of the overall protein size. For HbI, we elucidated the dynamics of complex allosteric transitions among transient intermediates. In particular, by applying structural refinement analysis based on rigid-body modeling, we found that the allosteric transition of HbI accompanies the rotation of quaternary structure and the contraction between two heme domains. By making use of the experimental and analysis methods presented in this Account, we envision that the TRXSS can be used to probe the structural dynamics of various proteins, allowing us to decipher the working mechanisms of their functions. Furthermore, when combined with femtosecond X-ray pulses generated from X-ray free electron lasers, TRXSS will gain access to ultrafast protein dynamics on sub-picosecond time scales. PMID- 26134249 TI - In Vitro Evaluation of Cu, Fe, and Zn Bioaccessibility in the Presence of Babassu Mesocarp. AB - In vitro gastrointestinal digestion of babassu mesocarp in the absence and presence of milk and lignin was performed to evaluate the bioaccessibility of Cu, Fe, and Zn. Extractions using NaOH solutions (pH 7 and 12) were carried out to evaluate the interactions of Cu(II), Fe(III), and Zn(II) with the extracted compounds and with the washed mesocarp. Studies using reference solutions showed a decrease in the free concentration of the elements in the presence of mesocarp. Phytate, a component present in the mesocarp, can be the main compound responsible for the elements' interactions with mesocarp. Lignin increases the elements' soluble fractions; however, the elements' concentrations in the dialyzed fractions, representing the bioaccessible portion, were very low. On the other hand, Cu, Fe, and Zn bioaccessibility in milk was not influenced by the mesocarp. PMID- 26134250 TI - Efficacy of the new infliximab biosimilar CT-P13 induction therapy in Crohn's disease and ulcerative colitis - experiences from a single center. AB - BACKGROUND: CT-P13 is the first biosimilar monoclonal antibody to infliximab (IFX); it has been approved for the same indications as its IFX counterpart in Hungary. The aim of this study was to assess the efficacy of CT-P13 induction therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Patients diagnosed with CD and UC, who were administered CT-P13, were prospectively enrolled. Disease activity was estimated at the start and after the induction therapy. In patients with UC, sigmoideoscopy was also performed at the end of the induction therapy. RESULTS: Eighteen CD and 21 UC patients were enrolled. Induction treatment was completed in 16 of the CD and 15 of the UC patients. In those with luminal CD, clinical response and remission was achieved in 6 (37.5%) and 8 (50%) of the patients at Week 8. In UC, clinical response and remission was achieved in 3 (20%) and 10 (66.7%) patients at Week 8. Mucosal healing was shown in 11 patients. CONCLUSIONS: This was the first study to prospectively evaluate the outcome of CT-P13 induction therapy in CD and UC. Our results confirm that induction with CT-P13 is safe and effective. PMID- 26134252 TI - Allergen immunotherapy: what's new, what's next? AB - Although three sublingual immunotherapy tablets have been approved in the USA and more are under study, it is not clear that sublingual immunotherapy tablets will answer the needs of many patients in the USA, and this is due to the limited number of allergens that will be offered. Alternatives that employ off-label, currently available extracts hold the greatest likelihood of entering the US allergy practice. Those approaches that employ recombinant technology to produce hypoallergenic products face a long and expensive pathway to approval. Which of the many approaches under study will make it to the market is presently not clear. PMID- 26134251 TI - cEBP Homologous Protein Expression in Macrophages Regulates the Magnitude and Duration of IL-6 Expression and Dextran Sodium Sulfate Colitis. AB - Cellular stress enhances inflammatory cytokine gene expression by inducing cEBP homologous protein (CHOP). Engaging cell stress via thapsigargin induced CHOP and selectively prolonged lipopolysaccharide-stimulated interleukin-6 (IL-6) expression in bone marrow-derived macrophages from wild-type (WT) but not CHOP knockout (KO) mice. To determine the impact of this mechanism in vivo we employed dextran sodium sulfate (DSS)-induced colitis in irradiated mice reconstituted with bone marrow from WT or CHOP KO mice. WT recipients of CHOP KO bone marrow exhibited more rapid recovery from disease than did mice reconstituted with WT bone marrow as reflected in increased survival, reduced clinical scores, and colonic histopathology. No differences in mesenteric lymph node cell populations were observed between mice with WT or CHOP KO bone marrow during colitis. CD11b(+) macrophages infiltrating the lamina propria were, however, reduced in DSS-treated mice reconstituted with CHOP KO bone marrow. CHOP expression was observed within the infiltrating inflammatory CD11b(+) macrophages. Furthermore, IL-6 expression within the inflamed colon was significantly lower in mice with CHOP-deficient bone marrow. Our findings indicate that CHOP expression in myeloid cells plays an important role in determining the magnitude and duration of inflammatory response in vivo by modulating expression of proinflammatory cytokines such as IL-6 in infiltrating macrophages. PMID- 26134253 TI - Agriproteomics of Bread Wheat: Comparative Proteomics and Network Analyses of Grain Size Variation. AB - Agriproteomics signifies the merging of agriculture research and proteomics systems science and is impacting plant research and societal development. Wheat is a frequently consumed foodstuff, has highly variable grain size that in effect contributes to wheat grain yield and the end-product quality. Very limited information is available on molecular basis of grain size due to complex multifactorial nature of this trait. Here, using liquid chromatography-mass spectrometry, we investigated the proteomics profiles from grains of wheat genotypes, Rye selection 111 (RS111) and Chinese spring (CS), which differ in their size. Significant differences in protein expression were found, including 33 proteins uniquely present in RS111 and 32 only in CS, while 54 proteins were expressed from both genotypes. Among differentially expressed proteins, 22 were upregulated, while 21 proteins were downregulated in RS111 compared to CS. Functional classification revealed their role in energy metabolism, seed storage, stress tolerance and transcription. Further, protein interactive network analysis was performed to predict the targets of identified proteins. Significantly different interactions patterns were observed between these genotypes with detection of proteins such as Cyp450, Sus2, and WRKY that could potentially affect seed size. The present study illustrates the potentials of agriproteomics as a veritable new frontier of plant omics research. PMID- 26134254 TI - Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum. AB - Major depressive disorder (MDD) is a highly prevalent, debilitating mental illness of importance for global health. However, its molecular pathophysiology remains poorly understood. Combined proteomics and metabolomics approaches should provide a comprehensive understanding of MDD's etiology. The present study reports novel "-omics" insights from a rodent model of MDD. Cerebellar samples from chronic mild stressed (CMS)-treated depressed rats and controls were compared with a focus on the differentially expressed proteins and metabolites using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and gas chromotography/mass spectrometry (GC-MS) metabolomics techniques, respectively. The combined analyses found significant alterations associated with cerebellar energy metabolism, as indicated by (1) abnormal amino acid metabolism accompanied by corresponding metabolic enzymatic alterations and disturbed protein turnover, (2) increased glycolytic and tricarboxylic acid (TCA) cycle enzyme levels paralleled by changes in the concentrations of associated metabolites, and (3) perturbation of ATP biosynthesis through adenosine accompanied by perturbation of the mitochondrial respiratory chain. To the best of our knowledge, this study is the first to integrate proteomics and metabolomics analyses to examine the pathophysiological mechanism(s) underlying MDD in a CMS rodent model of depression. These results can offer important insights into the pathogenesis of MDD. PMID- 26134255 TI - Botulinum Toxin as a Pain Killer: Players and Actions in Antinociception. AB - Botulinum neurotoxins (BoNTs) have been widely used to treat a variety of clinical ailments associated with pain. The inhibitory action of BoNTs on synaptic vesicle fusion blocks the releases of various pain-modulating neurotransmitters, including glutamate, substance P (SP), and calcitonin gene related peptide (CGRP), as well as the addition of pain-sensing transmembrane receptors such as transient receptor potential (TRP) to neuronal plasma membrane. In addition, growing evidence suggests that the analgesic and anti-inflammatory effects of BoNTs are mediated through various molecular pathways. Recent studies have revealed that the detailed structural bases of BoNTs interact with their cellular receptors and SNAREs. In this review, we discuss the molecular and cellular mechanisms related to the efficacy of BoNTs in alleviating human pain and insights on engineering the toxins to extend therapeutic interventions related to nociception. PMID- 26134257 TI - Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study. AB - The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox(r)) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect was assessed 2, 4, 8, 12, and 20 weeks after A/Ona (drooling problems (VAS), impact (0-7), treatment effect (0-5), unstimulated whole saliva (UWS) flow and composition)) and analyzed by two-way ANOVA. The effect was unchanged-moderate in A to moderate-marked in F. Changes in all parameters were significant in E and F, but with swallowing problems <=5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response. PMID- 26134256 TI - Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro Rehabilitation. AB - Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP) results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX) as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders including post-traumatic neuralgia, phantom limb, and complex regional pain syndrome with focal dystonia. The use of BTX-A could represent a novel therapeutic strategy in caring for neuropathic pain whenever common pharmacological tools have been ineffective. However, large and well designed clinical trials are needed to recommend BTX-A use in the relief of neuropathic pain. PMID- 26134258 TI - Three Peptide Modulators of the Human Voltage-Gated Sodium Channel 1.7, an Important Analgesic Target, from the Venom of an Australian Tarantula. AB - Voltage-gated sodium (NaV) channels are responsible for propagating action potentials in excitable cells. NaV1.7 plays a crucial role in the human pain signalling pathway and it is an important therapeutic target for treatment of chronic pain. Numerous spider venom peptides have been shown to modulate the activity of NaV channels and these peptides represent a rich source of research tools and therapeutic lead molecules. The aim of this study was to determine the diversity of NaV1.7-active peptides in the venom of an Australian Phlogius sp. tarantula and to characterise their potency and subtype selectivity. We isolated three novel peptides, MU-TRTX-Phlo1a, -Phlo1b and -Phlo2a, that inhibit human NaV1.7 (hNaV1.7). Phlo1a and Phlo1b are 35-residue peptides that differ by one amino acid and belong in NaSpTx family 2. The partial sequence of Phlo2a revealed extensive similarity with ProTx-II from NaSpTx family 3. Phlo1a and Phlo1b inhibit hNaV1.7 with IC50 values of 459 and 360 nM, respectively, with only minor inhibitory activity on rat NaV1.2 and hNaV1.5. Although similarly potent at hNaV1.7 (IC50 333 nM), Phlo2a was less selective, as it also potently inhibited rNaV1.2 and hNaV1.5. All three peptides cause a depolarising shift in the voltage dependence of hNaV1.7 activation. PMID- 26134259 TI - Culture-Independent Study of the Late-Stage of a Bloom of the Toxic Dinoflagellate Ostreopsis cf. ovata: Preliminary Findings Suggest Genetic Differences at the Sub-Species Level and Allow ITS2 Structure Characterization. AB - Available genomic data for the toxic, bloom-forming, benthic Ostreopsis spp. are traditionally obtained from isolates rather than from individuals originally present in environmental samples. Samples from the final phase of the first reported Ostreopsis bloom in European North Atlantic waters (Algarve, south coast of Portugal) were studied and characterized, using a culture-independent approach. In the first instance, a microscopy-based analysis revealed the intricate complexity of the samples. Then, we evaluated the adequacy of commonly used molecular tools (i.e., primers and nuclear ribosomal markers) for the study of Ostreopsis diversity in natural samples. A PCR-based methodology previously developed to identify/detect common Ostreopsis species was tested, including one new combination of existing PCR primers. Two sets of environmental rRNA sequences were obtained, one of them (1052 bp) with the newly tested primer set. These latter sequences encompass both the ITS1-5.8S-ITS2 region and the D1/D2 domain of the LSU rRNA gene, leading us to an accurate identification of ITS2. In turn, this allowed us to predict and show for the first time the ITS2 secondary structure of Ostreopsis. With 92 bp in length and a two-helix structure, the ITS2 of this genus revealed to be unique among the dinoflagellates. Both the PCR approach as the phylogenetic analyses allowed to place the Ostreopsis cells observed in the samples within the O. cf. ovata phylospecies' complex, discarding the presence of O. cf. siamensis. The (phylo)genetic results point out a certain level of nucleotide sequence divergence, but were inconclusive in relation to a possible geographic origin of the O. cf. ovata population from the Algarve's bloom. PMID- 26134260 TI - Fischer Indolizations as a Strategic Platform for the Total Synthesis of Picrinine. AB - Picrinine, which is a member of the akuammiline family of alkaloids, was first isolated in 1965 from the leaves of Alstonia scholaris. The natural product possesses a daunting polycyclic skeleton that contains a furanoindoline, a bridged [3.3.1]azabicycle, two N,O-acetal linkages, and six stereogenic centers. These structural features render picrinine a challenging and attractive target for total synthesis. This paper provides a full account of our synthetic forays toward picrinine, which culminates in the first total synthesis of this long standing target. Central to the success of our approach is the use of the Fischer indolization reaction to introduce the C7 quaternary stereocenter and the indoline nucleus of the natural product's scaffold. We probe some of the subtleties of this classic transformation by examining some of the most complex Fischer indolization substrates to date. Additionally, we describe various roadblocks encountered in our experimental efforts, which were successfully overcome to complete the total synthesis of picrinine. PMID- 26134261 TI - Fears, Uncertainties, and Hopes: Patient-Initiated Actions and Doctors' Responses During Oncology Interviews. AB - New cancer patients frequently raise concerns about fears, uncertainties, and hopes during oncology interviews. This study sought to understand when and how patients raise their concerns, how doctors responded to these patient-initiated actions, and implications for communication satisfaction. A subsampling of video recorded and transcribed encounters was investigated involving 44 new patients and 14 oncologists. Patients completed pre/post self-report measures about fears, uncertainties, and hopes as well as postevaluations of interview satisfaction. Conversation analysis was used to initially identify pairs of patient-initiated and doctor-responsive actions. A coding scheme was subsequently developed, and two independent coding teams, comprised of two coders each, reliably identified patient-initiated and doctor-responsive social actions. Interactional findings reveal that new cancer patients initiate actions much more frequently than previous research had identified, concerns are usually raised indirectly, and with minimal emotion. Doctors tend to respond to these concerns immediately, but with even less affect, and rarely partner with patients. From pre/post results, it was determined that the higher patients' reported fears, the higher their postvisit fears and lower their satisfaction. Patients with high uncertainty were highly proactive (e.g., asked more questions), yet reported even greater uncertainties after encounters. Hopeful patients also exited interviews with high hopes. Overall, new patients were very satisfied: oncology interviews significantly decreased patients' fears and uncertainties, while increasing hopes. Discussion raises key issues for improving communication and managing quality cancer care. PMID- 26134263 TI - miR-130a acts as a potential diagnostic biomarker and promotes gastric cancer migration, invasion and proliferation by targeting RUNX3. AB - MicroRNAs (miRNAs) are abnormally expressed in various types of cancer. miR-130a expression and function in gastric cancer has yet to be elucidated. The aim of the present study was to identify the miR-130a expression and function in gastric cancer. miR-130a expression was examined in gastric cancer cell lines and tissues by RT-qPCR. The diagnostic and prognostic significance of miR-130a in gastric cancer was analyzed by receiver-operating characteristic (ROC) curve and Kaplan Meier analysis. miR130a expression was identified and the diagnostic significance in the serum of gastric cancer patients and healthy controls was analyzed using RT-qPCR and ROC curves, respectively. A target gene for miR-130a was identified using luciferase reporter assays, and gastric cancer tumorigenesis ability was examined by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays. The results showed that miR-130a was upregulated in gastric cancer. The low-miR-130a group had significantly improved overall survival compared to the high-miR-130a group. Furthermore, the expression of miR-130a in plasma in gastric cancer patients was upregulated and diagnostic value for gastric cancer of miR-130a is more effective than the tumor markers carcinoembryonic antigen (CEA) and CA-199. miR-130a directly targeted runt related transcription factor 3 (RUNX3) and promoted gastric cancer tumorigenesis by targeting RUNX3. miR-130a may therefore be a useful marker for the diagnosis and prognosis of gastric cancer. Additionally, miR-130a was identified as an oncogene that promotes gastric cancer tumorigenesis by targeting RUNX3. PMID- 26134264 TI - Determinants of platelet count are different in patients with compensated and decompensated cirrhosis. AB - BACKGROUND & AIMS: Different mechanisms including portal hypertension and hypersplenism have been involved in the development of thrombocytopenia in cirrhosis. However, the relative contribution of each one is unknown. The aim was to evaluate simultaneously different mechanisms that determine platelet count in cirrhosis. METHODS: Cross-sectional study including cirrhotics (n = 120) with hepatic venous pressure gradient (HVPG) measurement. Samples were obtained from peripheral (P) veins to evaluate thrombopoietin (TPO), stem cell factor, hepatocyte growth factor (HGF), tumour necrosis factor, interleukin-(IL6) and (IL11) and from hepatic (H) veins to evaluate TPO. A subgroup (n = 72) had spleen volume estimation. H and P-TPO were also measured in non-cirrhotic patients (n = 15). RESULTS: Patients (Child A: 55, B: 43, C: 22) had a median platelet count of 81 000/mm(3) (IQR 60 500, 110 750), which correlated with spleen volume (r = 0.38, P < 0.001). Platelets were associated also to HVPG (r = -0.47, P = 0.004) and P-TPO (r = 0.31, P = 0.050) only in compensated patients. H-TPO decreased, and the proportion of patients with P-TPO > H-TPO increased, with the presence and the severity of liver disease. H-TPO was correlated with liver function (bilirubin r = -0.350, P < 0.001 and international normalized ratio r = -0.227, P = 0.011). Patients with H-TPO < P-TPO had higher levels of IL-11 and HGF. CONCLUSION: Platelet count in cirrhosis is associated mainly to spleen volume, although portal hypertension as estimated by HVPG and liver function plays a significant role in compensated patients. H-TPO and the proportion of patients with P-TPO > H-TPO were associated to the presence and severity of liver disease. PMID- 26134262 TI - Predictive biomarkers in precision medicine and drug development against lung cancer. AB - The molecular characterization of various cancers has shown that cancers with the same origins, histopathologic diagnoses, and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis. A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been identified. Therapeutic agents targeting some of these cancer drivers have been successfully developed, resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer patients. However, because such therapeutic drugs often benefit only a limited number of patients, the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies. Thus, biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug development. This review discusses the molecular heterogeneity of lung cancer pathogenesis; predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1), and immune checkpoints; biomarkers associated with resistance to these therapeutics; and approaches to identify predictive biomarkers in anticancer drug development. The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate. Additionally, such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits. PMID- 26134266 TI - Physician burnout: can we make a difference together? AB - BACKGROUND: Despite the documented prevalence and clinical ramifications of physician distress, few rigorous studies have tested interventions to address the problem. METHODS: OBJECTIVE: To test the hypothesis that an intervention involving a facilitated physician small-group curriculum would result in improvement in well-being. DESIGN: A randomized clinical trial of practicing physicians. Additional data were collected on nontrial participants responding to annual surveys timed to coincide with the trial surveys. SETTING: Department of Medicine at the Mayo Clinic in Rochester, Minnesota between September 2010 and June 2012. PARTICIPANTS: The study involved 74 practicing physicians in the Department of Medicine and 350 nontrial participants responding to annual surveys. INTERVENTIONS: The intervention involved 19 biweekly facilitated physician discussion groups incorporating elements of mindfulness, reflection, shared experience, and small-group learning for 9 months. Protected time (1 hour of paid time every other week) for participants was provided by the institution. OUTCOMES: Meaning in work, empowerment and engagement in work, burnout, symptoms of depression, quality of life, and job satisfaction were assessed using validated metrics. RESULTS: Empowerment and engagement at work increased by 5.3 points in the intervention arm vs. a 0.5-point decline in the control arm by 3 months after the study (P = .04), an improvement sustained at 12 months (+5.5 vs. +1.3 points; P = .03). Rates of high depersonalization at 3 months had decreased by 15.5 % in the intervention arm vs. a 0.8 % increase in the control arm (P = .004). This difference was also sustained at 12 months (9.6 % vs. 1.5 % decrease; P = .02). No statistically significant differences in stress, symptoms of depression, overall quality of life, or job satisfaction were seen. In additional comparisons including the nontrial physician cohort, the proportion of participants strongly agreeing that their work was meaningful increased 6.3 % in the study intervention arm but decreased 6.3 % in the study control arm and 13.4 % in the nonstudy cohort (P = .04). Rates of depersonalization, emotional exhaustion, and overall burnout decreased substantially in the trial intervention arm, decreased slightly in the trial control arm, and increased in the nontrial cohort (P = .03, P = .007, and P = .002 for each outcome, respectively). CONCLUSIONS: An intervention for physicians based on a facilitated small-group curriculum improved meaning and engagement in work and reduced depersonalization, with sustained results 12 months after the study. PMID- 26134265 TI - Thymoquinone inhibits TNF-alpha-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation. AB - Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine produced by monocytes/macrophage that plays a pathological role in rheumatoid arthritis (RA). In this study, we investigate the effect of thymoquinone (TQ), a phytochemical found in Nigella sativa, in regulating TNF-alpha-induced RA synovial fibroblast (RA-FLS) activation. Treatment with TQ (1-5MUM) had no marked effect on the viability of human RA-FLS. Pre-treatment of TQ inhibited TNF-alpha induced interleukin-6 (IL-6) and IL-8 production and ICAM-1, VCAM-1, and cadherin 11 (Cad-11) expression in RA-FLS (p<0.01). Evaluation of the signaling events showed that TQ inhibited TNF-alpha-induced phospho-p38 and phospho-JNK expression, but had no inhibitory effect on NF-kappaB pathway, in RA-FLS (p<0.05; n=4). Interestingly, we observed that selective down-regulation of TNF-alpha induced phospho-p38 and phospho-JNK activation by TQ is elicited through inhibition of apoptosis-regulated signaling kinase 1 (ASK1). Furthermore, TNF alpha selectively induced phosphorylation of ASK1 at Thr845 residue in RA-FLS, which was inhibited by TQ pretreatment in a dose dependent manner (p<0.01). Pre treatment of RA-FLS with ASK1 inhibitor (TC ASK10), blocked TNF-alpha induced expression of ICAM-1, VCAM-1, and Cad-11. Our results suggest that TNF-alpha induced ASK1-p38/JNK pathway is an important mediator of cytokine synthesis and enhanced expression of adhesion molecule in RA-FLS and TQ, by selectively inhibiting this pathway, may have a potential therapeutic value in regulating tissue destruction observed in RA. PMID- 26134267 TI - High pressure balloon dilation for vesicourethral anastomotic strictures after radical prostatectomy. AB - BACKGROUND: Vesicourethral anastomotic stricture (VAS) is a rare but serious complication following radical prostatectomy (RP), and various types of managements for VAS have been proposed. We investigated the efficacy of transurethral balloon dilation in the management of VAS after RP. METHODS: A total of 128 consecutive patients underwent open RP at our hospital between 2008 and 2013; of these, 10 patients (7.8%) developed VAS. Transurethral balloon dilation was performed in all 10 patients, using a high pressure balloon catheter under fluoroscopic and endoscopic guidance. Follow-up endoscopy was performed, and patients in whom the stricture had recurred underwent repeat dilation. We retrospectively evaluated the management of VAS and short-term efficacy of high pressure balloon dilation. RESULTS: The mean time from RP to diagnosis of VAS was 9 months (2-40 months); eight patients (80%) were diagnosed within 6 months of RP. Balloon dilation of VAS was technically successful in all patients, and no perioperative complications were recorded. The median follow-up after balloon dilation was 24 months (7-67 months). There was no recurrence of VAS in eight patients (80%) after the first balloon dilation, and all patients were controlled within the twice. CONCLUSION: High pressure balloon dilation is a highly effective and minimally invasive procedure for treating VAS. PMID- 26134268 TI - Eliminating the dose-rate effect in a radiochromic silicone-based 3D dosimeter. AB - Comprehensive dose verification, such as 3D dosimetry, may be required for safe introduction and use of advanced treatment modalities in radiotherapy. A radiochromic silicone-based 3D dosimetry system has recently been suggested, though its clinical use has so far been limited by a considerable dose-rate dependency of the dose response. In this study we have investigated the dose-rate dependency with respect to the chemical composition of the dosimeter. We found that this dependency was reduced with increasing dye concentration, and the dose response was observed to be identical for dosimeters irradiated with 2 and 6 Gy min(-1) at concentrations of 0.26% (w/w) dye and 1% (w/w) dye solvent. Furthermore, for the optimized dosimeter formulation, no dose-rate effect was observed due to the attenuation of the beam fluence with depth. However, the temporal stability of the dose response decreased with dye concentration; the response was reduced by (62 +/- 1)% within approximately 20 h upon irradiation, at the optimal chemical composition and storage at room temperature. In conclusion, this study presents a chemical composition for a dose-rate independent silicone dosimeter which has considerably improved the clinical applicability of such dosimeters, but at the cost of a decreased stability. PMID- 26134270 TI - Carry-Over or Compensation? The Impact of Winter Harshness and Post-Winter Body Condition on Spring-Fattening in a Migratory Goose Species. AB - Environmental conditions at one point of the annual cycle of migratory species may lead to cross-seasonal effects affecting fitness in subsequent seasons. Based on a long-term mark-resighting dataset and scoring of body condition in an arctic breeding goose species, we demonstrate a substantial effect of winter harshness on post-winter body condition. However, this effect was compensated along the spring migration corridor, and did not persist long enough to influence future reproduction. This highlights the importance of temporal scale when assessing impacts of environmental effects, and suggests a state-dependent physiological mechanism adjusting energy accumulation according to internal energy stores carried into spring. In support of these findings, the development of body condition was unaffected by whether geese used supplementary feeding sites or not. While there was no effect of winter harshness on the average population pre breeding body condition, individual variations in early spring body condition (probably related to different life-histories) were partly traceable throughout spring. This strongly indicates a carry-over effect on the individual level, possibly related to differences in dominance, site use, disturbance or migration strategy, which may potentially affect future reproduction. PMID- 26134269 TI - Reducing the impact of influenza-associated secondary pneumococcal infections. AB - When administered prophylactically, we show that the Toll-like receptor-2 (TLR-2) agonist PEG-Pam2Cys (pegylated-S-(2,3-bis(palmitoyloxy)propyl)cysteine) not only mediates potent anti-viral activity against influenza virus but also reduces the impact of secondary infections with Streptococcus pneumoniae (the pneumococcus) by reducing (i) pulmonary viral and bacterial burdens, (ii) the levels of proinflammatory cytokines that normally accompany influenza and S. pneumoniae secondary infections and (iii) the vascular permeability of the pulmonary tract that can allow bacterial invasion of the blood in mice. We also show that an inactivated detergent-disrupted influenza virus vaccine formulated with the Pam2Cys-based adjuvant R4-Pam2Cys provides the host with both immediate and long term protection against secondary pneumococcal infections following influenza virus infection through innate and specific immune mechanisms, respectively. Vaccinated animals generated influenza virus-specific immune responses that provided the host with long-term protection against influenza virus and its sequelae. This vaccine, which generates an immediate response, provides an additional countermeasure, which is ideal for use even in the midst of an influenza outbreak. PMID- 26134271 TI - Synthesis, properties and applications of 2D non-graphene materials. AB - As an emerging class of new materials, two-dimensional (2D) non-graphene materials, including layered and non-layered, and their heterostructures are currently attracting increasing interest due to their promising applications in electronics, optoelectronics and clean energy. In contrast to traditional semiconductors, such as Si, Ge and III-V group materials, 2D materials show significant merits of ultrathin thickness, very high surface-to-volume ratio, and high compatibility with flexible devices. Owing to these unique properties, while scaling down to ultrathin thickness, devices based on these materials as well as artificially synthetic heterostructures exhibit novel and surprising functions and performances. In this review, we aim to provide a summary on the state-of-the art research activities on 2D non-graphene materials. The scope of the review will cover the preparation of layered and non-layered 2D materials, construction of 2D vertical van der Waals and lateral ultrathin heterostructures, and especially focus on the applications in electronics, optoelectronics and clean energy. Moreover, the review is concluded with some perspectives on the future developments in this field. PMID- 26134272 TI - Ischemic preconditioning maintains the immunoreactivities of glucokinase and glucokinase regulatory protein in neurons of the gerbil hippocampal CA1 region following transient cerebral ischemia. AB - Glucokinase (GK) is involved in the control of blood glucose homeostasis. In the present study, the effect of ischemic preconditioning (IPC) on the immunoreactivities of GK and its regulatory protein (GKRP) following 5 min of transient cerebral ischemia was investigated in gerbils. The gerbils were randomly assigned to four groups (sham-operated group, ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated group). IPC was induced by subjecting the gerbils to 2 min of ischemia, followed by 1 day of recovery. In the ischemia-operated group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) at 5 days post ischemia; however, in the IPC+ischemia-operated group, the neurons in the SP were well protected. Following immunohistochemical investigation, the immunoreactivities of GK and GKRP in the neurons of the SP were markedly decreased in the CA1, but not the CA2/3, from 2 days post-ischemia, and were almost undetectable in the SP 5 days post-ischemia. In the IPC + ischemia operated group, the immunoreactivities of GK and GKRP in the SP of the CA1 were similar to those in the sham-group. In brief, the findings of the present study demonstrated that IPC notably maintained the immunoreactivities of GK and GKRP in the neurons of the SP of CA1 following ischemia-reperfusion. This indicated that GK and GKRP may be necessary for neuron survival against transient cerebral ischemia. PMID- 26134273 TI - HPMA-based polymeric micelles for curcumin solubilization and inhibition of cancer cell growth. AB - Curcumin (CM) has been reported as a potential anticancer agent. However, its pharmaceutical applications as therapeutic agent are hampered because of its poor aqueous solubility. The present study explores the advantages of polymeric micelles composed of block copolymers of methoxypoly(ethylene glycol) (mPEG) and N-(2-hydroxypropyl) methacrylamide (HPMA) modified with monolactate, dilactate and benzoyl side groups to enhance CM solubility and inhibitory activity against cancer cells. Amphiphilic block copolymers, omega-methoxypoly(ethylene glycol)-b (N-(2-benzoyloxypropyl) methacrylamide) (PEG-HPMA-Bz) were synthesized and characterized by (1)H NMR and GPC. One polymer with a molecular weight of 28,000Da was used to formulate CM and compared with other aromatic substituted polymers. CM was loaded by a fast heating method (PEG-HPMA-DL and PEG-HPMA-Bz-L) and a nanoprecipitation method (PEG-HPMA-Bz). Physicochemical characteristics and cytotoxicity/cytocompatibility of the CM loaded polymeric micelles were evaluated. It was found that HPMA-based polymeric micelles significantly enhanced the solubility of CM. The PEG-HPMA-Bz micelles showed the best solubilization properties. CM loaded polymeric micelles showed sustained release of the loading CM for more than 20days. All of CM loaded polymeric micelles formulations showed a significantly potent cytotoxic effect against three cancer cell lines. HPMA based polymeric micelles are therefore promising nanodelivery systems of CM for cancer therapy. PMID- 26134274 TI - Type VI Secretion System Transports Zn2+ to Combat Multiple Stresses and Host Immunity. AB - Type VI secretion systems (T6SSs) are widespread multi-component machineries that translocate effectors into either eukaryotic or prokaryotic cells, for virulence or for interbacterial competition. Herein, we report that the T6SS-4 from Yersinia pseudotuberculosis displays an unexpected function in the transportation of Zn2+ to combat diverse stresses and host immunity. Environmental insults such as oxidative stress induce the expression of T6SS-4 via OxyR, the transcriptional factor that also regulates many oxidative response genes. Zinc transportation is achieved by T6SS-4-mediated translocation of a novel Zn2+-binding protein substrate YezP (YPK_3549), which has the capacity to rescue the sensitivity to oxidative stress exhibited by T6SS-4 mutants when added to extracellular milieu. Disruption of the classic zinc transporter ZnuABC together with T6SS-4 or yezP results in mutants that almost completely lost virulence against mice, further highlighting the importance of T6SS-4 in resistance to host immunity. These results assigned an unconventional role to T6SSs, which will lay the foundation for studying novel mechanisms of metal ion uptake by bacteria and the role of this process in their resistance to host immunity and survival in harmful environments. PMID- 26134276 TI - Similarity computation strategies in the microRNA-disease network: a survey. AB - Various microRNAs have been demonstrated to play roles in a number of human diseases. Several microRNA-disease network reconstruction methods have been used to describe the association from a systems biology perspective. The key problem for the network is the similarity computation model. In this article, we reviewed the main similarity computation methods and discussed these methods and future works. This survey may prompt and guide systems biology and bioinformatics researchers to build more perfect microRNA-disease associations and may make the network relationship clear for medical researchers. PMID- 26134275 TI - Inhibition of P-glycoprotein Gene Expression and Function Enhances Triptolide induced Hepatotoxicity in Mice. AB - Triptolide (TP) is the major active principle of Tripterygium wilfordii Hook f. and very effective in treatment of autoimmune diseases. However, TP induced hepatotoxicity limited its clinical applications. Our previous study found that TP was a substrate of P-glycoprotein and its hepatobiliary clearance was markedly affected by P-gp modulation in sandwich-cultured rat hepatocytes. In this study, small interfering RNA (siRNA) and specific inhibitor tariquidar were used to investigate the impact of P-gp down regulation on TP-induced hepatotoxicity. The results showed that when the function of P-gp was inhibited by mdr1a-1 siRNA or tariquidar, the systemic and hepatic exposures of TP were significantly increased. The aggravated hepatotoxicity was evidenced with the remarkably lifted levels of serum biomarkers (ALT and AST) and pathological changes in liver. The other toxicological indicators (MDA, SOD and Bcl-2/Bax) were also significantly changed by P-gp inhibition. The data analysis showed that the increase of TP exposure in mice was quantitatively correlated to the enhanced hepatotoxicity, and the hepatic exposure was more relevant to the toxicity. P-gp mediated clearance played a significant role in TP detoxification. The risk of herb-drug interaction likely occurs when TP is concomitant with P-gp inhibitors or substrates in clinic. PMID- 26134277 TI - The Profile of T Helper Subsets in Bone Marrow Microenvironment Is Distinct for Different Stages of Acute Myeloid Leukemia Patients and Chemotherapy Partly Ameliorates These Variations. AB - BACKGROUND: T helper (Th) cells immune regulation is important for the pathogenesis of acute myeloid leukemia (AML). Recurrent Th abnormalities in AML peripheral blood were reported, while the comprehensive status of various Th subsets is rarely investigated in bone marrow (BM) microenvironment which is the origin of AML leukemic blast cells. METHODS: BM was extracted from 48 newly diagnosed (ND), 34 complete-remission (CR), 19 relapsed-refractory AML patients and 15 controls. Slight iron deficiency anemia patients were used as controls. Th subsets frequencies were examined by flow cytometry. BM plasma Th-associated cytokines levels were determined by ELISA. The expression of key transcription factor was examined by RT-PCR. RESULTS: Th22, Th17, Th1, Th2 cells, IL-22 and RORC expression were significantly decreased, while Treg cells, related cytokine IL-10 and transcription factor Foxp3 were markedly elevated in ND compared to CR patients or controls. Meanwhile, the imbalanced Th1/Th2 and Th17/Treg ratio were observed in ND and relapsed-refractory patients. Negative correlation between Th1 or Th2 and peripheral WBC, between Th17/Treg or Th1/Th2 and leukemic blast existed in ND patients. Moreover, chemotherapy ameliorated these variations. CONCLUSION: Th subsets in BM are distinct for different stages of AML and chemotherapy partly ameliorates the abnormality. Our findings suggest that these cells and cytokines may be implicated in AML pathogenesis and provided therapeutic insights. PMID- 26134278 TI - Detection of antibodies against fimbria type 3 (Fim3) is useful diagnostic assay for pertussis. AB - Isolation of Bordetella pertussis and detection of the pertussis genome are not always successful because of low bacterial loads in adult patients with pertussis. Antibodies against pertussis toxin (PT) are measured but have low sensitivity in vaccinated subjects. There is no reliable diagnostic method at present. In this study, a fluorescent-EIA against several pertussis antigens and genome detection were investigated to establish clinical laboratory diagnostic methods for pertussis. The study was conducted in an outpatient clinic between September 2007 and 2013. Subjects consisted of 209 patients including adults suspected of pertussis and 35 staff members of the clinic. Loop-mediated isothermal amplification (LAMP) was performed to detect the pertussis genome in 5' UTR of the pertussis toxin (PT) gene. The catalytic region of the adenylate cyclase toxin (catACT), C-terminal of filamentous hemagglutinin (cFHA), and type 3 fimbria (Fim3) were selected, which are not pertussis vaccine component. Conventional PT and FHA antibodies were examined together with type 2 fimbria (Fim2) antibodies, and these are vaccine antigens. Pertussis DNA was detected in 23 (11%) out of 209. Detection sensitivity was high in young infants. Antibodies against Fim3 showed a higher positive rate in all age groups. Staff members at the pediatric outpatient clinic showed serological booster responses in Fim2 and Fim3 antibodies more sensitively than those in PT antibodies during outbreaks. LAMP was useful for detecting the pertussis genome in young infants, whereas a serological assay for fluorescent-EIA against Fim2 and Fim3 was preferable for adolescents and adults. PMID- 26134279 TI - Do We Perceive Others Better than Ourselves? A Perceptual Benefit for Noise Vocoded Speech Produced by an Average Speaker. AB - In different tasks involving action perception, performance has been found to be facilitated when the presented stimuli were produced by the participants themselves rather than by another participant. These results suggest that the same mental representations are accessed during both production and perception. However, with regard to spoken word perception, evidence also suggests that listeners' representations for speech reflect the input from their surrounding linguistic community rather than their own idiosyncratic productions. Furthermore, speech perception is heavily influenced by indexical cues that may lead listeners to frame their interpretations of incoming speech signals with regard to speaker identity. In order to determine whether word recognition evinces similar self-advantages as found in action perception, it was necessary to eliminate indexical cues from the speech signal. We therefore asked participants to identify noise-vocoded versions of Dutch words that were based on either their own recordings or those of a statistically average speaker. The majority of participants were more accurate for the average speaker than for themselves, even after taking into account differences in intelligibility. These results suggest that the speech representations accessed during perception of noise-vocoded speech are more reflective of the input of the speech community, and hence that speech perception is not necessarily based on representations of one's own speech. PMID- 26134280 TI - Reaching women where they are: eliminating the initial in-person medical abortion visit. AB - The requirement that every woman desiring medical abortion must come in person to a clinical facility to obtain the drugs is a substantial barrier for many women. To eliminate this requirement in the United States, two key components of the standard initial visit would need to be restructured. First, alternatives to ultrasound and pelvic exam would need to be identified for ensuring that gestational age is within the limit for safe and effective treatment. This is probably feasible: for example, data from a large study suggest that in selected patients menstrual history is highly sensitive for this purpose. Second, the Food and Drug Administration would need to remove the medically unwarranted restriction on distribution of mifepristone. These two changes could allow provision of the service by a broader range of providers in nontraditional venues or even by telemedicine. Such options could have profound benefits in reducing cost and expanding access to abortion. PMID- 26134281 TI - From qualified physician to licensed health care professional: the time has come to change mifepristone's label. PMID- 26134283 TI - Double-observer line transect surveys with Markov-modulated Poisson process models for animal availability. AB - We develop maximum likelihood methods for line transect surveys in which animals go undetected at distance zero, either because they are stochastically unavailable while within view or because they are missed when they are available. These incorporate a Markov-modulated Poisson process model for animal availability, allowing more clustered availability events than is possible with Poisson availability models. They include a mark-recapture component arising from the independent-observer survey, leading to more accurate estimation of detection probability given availability. We develop models for situations in which (a) multiple detections of the same individual are possible and (b) some or all of the availability process parameters are estimated from the line transect survey itself, rather than from independent data. We investigate estimator performance by simulation, and compare the multiple-detection estimators with estimators that use only initial detections of individuals, and with a single-observer estimator. Simultaneous estimation of detection function parameters and availability model parameters is shown to be feasible from the line transect survey alone with multiple detections and double-observer data but not with single-observer data. Recording multiple detections of individuals improves estimator precision substantially when estimating the availability model parameters from survey data, and we recommend that these data be gathered. We apply the methods to estimate detection probability from a double-observer survey of North Atlantic minke whales, and find that double-observer data greatly improve estimator precision here too. PMID- 26134282 TI - Effect of long-term prophylaxis in the development of cytomegalovirus-specific T cell immunity in D+/R- solid organ transplant recipients. AB - BACKGROUND: This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. METHODS: A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon gamma-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively). CONCLUSIONS: The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease. PMID- 26134284 TI - A new class of chiral materials hosting magnetic skyrmions beyond room temperature. AB - Skyrmions, topologically protected vortex-like nanometric spin textures in magnets, have been attracting increasing attention for emergent electromagnetic responses and possible technological applications for spintronics. In particular, metallic magnets with chiral and cubic/tetragonal crystal structure may have high potential to host skyrmions that can be driven by low electrical current excitation. However, experimental observations of skyrmions have been limited to below room temperature for the metallic chiral magnets, specifically for the MnSi type B20 compounds. Towards technological applications, transcending this limitation is crucial. Here we demonstrate the formation of skyrmions with unique spin helicity both at and above room temperature in a family of cubic chiral magnets: beta-Mn-type Co-Zn-Mn alloys with a different chiral space group from that of B20 compounds. Lorentz transmission electron microscopy, magnetization and small-angle neutron scattering measurements unambiguously reveal formation of a skyrmion crystal under application of a magnetic field in both thin-plate and bulk forms. PMID- 26134285 TI - Hydroxychloroquine Destabilizes Phospho-S6 in Human Renal Carcinoma Cells. AB - mTOR inhibitors are used to treat metastatic renal cell cancer (RCC), but most patients eventually become resistant. One possible mechanism for resistance is upregulation of autophagy, a pathway that helps recycle intracellular proteins and promotes cell survival. Hydroxychloroquine (HCQ), a potent autophagy inhibitor used to treat malaria and autoimmune disorders, is currently being studied in the context of cancer treatment. Here, we have investigated the effects of HCQ on three different renal carcinoma derived cell lines. We found that HCQ treatment inhibits RCC cell growth, promotes apoptosis, inhibits mitochondrial oxygen consumption, and increases rates of glycolysis. To understand the molecular mechanism behind these effects, we examined various nodes in the mTOR pathway and compared the effects of HCQ with the effects of the mTOR inhibitor RAD001. A key downstream readout of the pathway, phospho-S6 protein, was inhibited by both HCQ and RAD001. However, the upstream kinase, P70S6K was only inhibited by RAD001 and not HCQ, suggesting that the block by HCQ was downstream of P70S6K. Treatment with the proteasome inhibitor bortezomib restored phospho-S6 levels, suggesting that the reduction of phospho-S6 is caused by increased degradation of phospho-S6, but not total S6. Surprisingly, treatment with other autophagy inhibitors did not exhibit the same effects. Our findings suggest that HCQ causes the down-regulation of phospho-S6 in RCC cell lines via a novel mechanism that is not shared with other autophagy inhibitors. PMID- 26134287 TI - Corrosion control: general discussion. PMID- 26134286 TI - 2-Deoxy-d-Glucose Can Complement Doxorubicin and Sorafenib to Suppress the Growth of Papillary Thyroid Carcinoma Cells. AB - Tumor cells display a shift in energy metabolism from oxidative phosphorylation to aerobic glycolysis. A subset of papillary thyroid carcinoma (PTC) is refractory to surgery and radioactive iodine ablation. Doxorubicin and sorafenib are the drugs of choice for treating advanced thyroid cancer but both induce adverse effects. In this study, we assessed the anti-cancer activity of 2-deoxy-d glucose (2-DG) alone and in combination with doxorubicin or sorafenib in PTC cell lines with (BCPAP) and without (CG3) the BRAFV600E mutation. BCPAP cells were more glycolytic than CG3 cells, as evidenced by their higher extracellular l lactate production, lower intracellular ATP level, lower oxygen consumption rate (OCR), and lower ratio of OCR/extracellular acidification rate. However, dose dependent reduction in cell viability, intracellular ATP depletion, and extracellular l-lactate production were observed after 2-DG treatment. Regression analysis showed that cell growth in both cell lines was dependent on ATP generation. 2-DG increased the chemosensitivity of BCPAP and CG3 cell lines to doxorubicin and sorafenib. These results demonstrate that the therapeutic effects of low combined doses of 2-DG and doxorubicin or sorafenib are similar to those of high doses of doxorubicin or sorafenib alone in PTC cell lines regardless of the BRAFV600E mutation. PMID- 26134289 TI - Risk factors and potential preventive measures for nephropatia epidemica in Sweden 2011-2012: a case-control study. AB - INTRODUCTION: Nephropatia epidemica (NE), a relatively mild form of hemorrhagic fever with renal syndrome caused by the Puumala virus (PUUV), is endemic in northern Sweden. We aim to study the risk factors associated with NE in this region. METHODS: We conducted a matched case-control study between June 2011 and July 2012. We compared confirmed NE cases with randomly selected controls, matched by age, sex, and place of infection or residence. We analyzed the association between NE and several occupational, environmental, and behavioral exposures using conditional logistic regression. RESULTS: We included in the final analysis 114 cases and 300 controls, forming 246 case-control pairs. Living in a house with an open space beneath, making house repairs, living less than 50 m from the forest, seeing rodents, and smoking were significantly associated with NE. CONCLUSION: Our results could orient public health policies targeting these risk factors and subsequently reduce the NE burden in the region. PMID- 26134288 TI - Comparative Anterior Pituitary miRNA and mRNA Expression Profiles of Bama Minipigs and Landrace Pigs Reveal Potential Molecular Network Involved in Animal Postnatal Growth. AB - The anterior pituitary is the most important endocrine organ modulating animal postnatal growth, mainly by controlling growth hormone (GH) gene transcription, synthesis, and secretion. As an ideal model for animal postnatal growth studies, the Bama minipig is characterized as having a lower growth performance and fewer individual differences compared with larger pig breeds. In this study, anterior pituitaries from Bama minipig and Landrace pig were used for miRNA and mRNA expression profile analysis using miRNA microarrays and mRNA-seq. Consequently, a total of 222 miRNAs and 12,909 transcripts were detected, and both miRNAs and mRNAs in the two breeds showed high correlation (r > 0.97). Additionally, 41 differentially expressed miRNAs and 2,254 transcripts were identified. Pathways analysis indicated that 32 pathways significantly differed in the two breeds. Importantly, two GH-regulation-signalling pathways, cAMP and inositol 1, 4, 5 triphosphate (IP3), and multiple GH-secretion-related transcripts were significantly down-regulated in Bama minipigs. Moreover, TargetScan and RNAHybrid algorithms were used for predicting differentially expressed miRNAs (DE miRNAs) and differentially expressed mRNAs (DE mRNAs) interaction. By examining their fold-changes, interestingly, most DE miRNA-DE mRNA target pairs (63.68-71.33%) presented negatively correlated expression pattern. A possible network among miRNAs, mRNAs, and GH-regulation pathways was also proposed. Among them, two miRNA-mRNA interactions (Y-47 targets FSHB; ssc-miR-133a-3p targets GNAI3) were validated by dual-luciferase assay. These data will be helpful in understanding the possible molecular mechanisms involved in animal postnatal growth. PMID- 26134290 TI - Application of nanomaterials in the bioanalytical detection of disease-related genes. AB - In the diagnosis of genetic diseases and disorders, nanomaterials-based gene detection systems have significant advantages over conventional diagnostic systems in terms of simplicity, sensitivity, specificity, and portability. In this review, we describe the application of nanomaterials for disease-related genes detection in different methods excluding PCR-related method, such as colorimetry, fluorescence-based methods, electrochemistry, microarray methods, surface-enhanced Raman spectroscopy (SERS), quartz crystal microbalance (QCM) methods, and dynamic light scattering (DLS). The most commonly used nanomaterials are gold, silver, carbon and semiconducting nanoparticles. Various nanomaterials based gene detection methods are introduced, their respective advantages are discussed, and selected examples are provided to illustrate the properties of these nanomaterials and their emerging applications for the detection of specific nucleic acid sequences. PMID- 26134291 TI - Nanozyme-strip for rapid local diagnosis of Ebola. AB - Ebola continues to rage in West Africa. In the absence of an approved vaccine or treatment, the priority in controlling this epidemic is to promptly identify and isolate infected individuals. To this end, a rapid, highly sensitive, and easy-to use test for Ebola diagnosis is urgently needed. Here, by using Fe3O4 magnetic nanoparticle (MNP) as a nanozyme probe, we developed a MNP-based immunochromatographic strip (Nanozyme-strip), which detects the glycoprotein of Ebola virus (EBOV) as low as 1 ng/mL, which is 100-fold more sensitive than the standard strip method. The sensitivity of the Nanozyme-strip for EBOV detection and diagnostic accuracy for New Bunyavirus clinical samples is comparable with ELISA, but is much faster (within 30 min) and simpler (without need of specialist facilities). The results demonstrate that the Nanozyme-strip test can rapidly and sensitively detect EBOV, providing a valuable simple screening tool for diagnosis of infection in Ebola-stricken areas. PMID- 26134292 TI - Integrated OLED as excitation light source in fluorescent lateral flow immunoassays. AB - The integration of organic light emitting diodes (OLEDs) as excitation light sources for quantum dot-based fluorescent lateral flow immunoassay systems (LFIA) was investigated. This approach has the potential to deliver a sensitive visible detection scheme for low-cost, disposable lab-on-chip point-of-care (POC) diagnosis system. Thin film phosphorescent green OLEDs fabricated on plastic substrates were integrated on-chip to excite the test line of a quantum dot-based LFIA (QD-LFIA). OLEDs were fabricated by sequential deposition of organic thin films (total of ~100 nm) onto ITO-coated PET substrates. CdSe/ZnS QDs emitting at 655 nm and Au nanoparticles (NP - 10 nm size) conjugated antibodies were used for the fluorescence QD-LFIA and conventional reflection-mode Au NP-LFIA, respectively. Thin plastic color light filters were integrated for filtering the excitation light source and, thereby, increasing the contrast of the emitted light for optimized visual detection. Integration of the OLED and color filters with the analytical membrane was achieved using adhesive techniques facilitated by the planar nature of the layers, which suggests possible large scale manufacturing using roll-to-roll processing. Gray scale analysis from digital images captured with a digital camera was used to quantify the visual sensitivity. The signal intensity, signal-to-noise ratio (SNR) and the limit of detection (LOD) of OLED integrated QD-LFIAs were compared to Au NP LFIAs. OLED QD LFIA exhibited superior performance in all signal aspects: 7-8* higher signal intensity and SNR, and a 7* lower LOD of 3 nM (measured at S/N=3). These results demonstrate the potential of OLED-integrated in LFIA devices for obtaining sensitive, fast and low-cost POC diagnostics. PMID- 26134293 TI - Capturing coevolutionary signals inrepeat proteins. AB - BACKGROUND: The analysis of correlations of amino acid occurrences in globular domains has led to the development of statistical tools that can identify native contacts - portions of the chains that come to close distance in folded structural ensembles. Here we introduce a direct coupling analysis for repeat proteins - natural systems for which the identification of folding domains remains challenging. RESULTS: We show that the inherent translational symmetry of repeat protein sequences introduces a strong bias in the pair correlations at precisely the length scale of the repeat-unit. Equalizing for this bias in an objective way reveals true co-evolutionary signals from which local native contacts can be identified. Importantly, parameter values obtained for all other interactions are not significantly affected by the equalization. We quantify the robustness of the procedure and assign confidence levels to the interactions, identifying the minimum number of sequences needed to extract evolutionary information in several repeat protein families. CONCLUSIONS: The overall procedure can be used to reconstruct the interactions at distances larger than repeat-pairs, identifying the characteristics of the strongest couplings in each family, and can be applied to any system that appears translationally symmetric. PMID- 26134297 TI - Improved method for rapid detection of phthalates in bottled water by gas chromatography-mass spectrometry. AB - An improved gas chromatography-mass spectrometry (GC-MS) method for simple, rapid and precise quantification of phthalates in drinking water is presented. This method was validated for bis (2-n-butoxyethyl) phthalate (DBEP), bis (2-n ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP), di-butyl phthalate (DBP), diethyl phthalate (DEP), dihexyl phthalate (DHP), dimethyl phthalate (DMP), di-n-octyl phthalate (DNOP) and dinonyl phthalate (DINP). Linearity of 0.9984>r(2)>0.9975 in the range of 0.075-4.8MUg/mL for the selected phthalates was obtained. Accuracy values were in the range of 93-114% and RSD% for the analysis of 1.2MUg/mL of each phthalate was below 2.3% (n=9). This new method design has significantly improved the detection in terms of rapidity, specificity, repeatability and accuracy compared to available methods. The procedure has been applied to the analyses of three different brands of commercially available bottled mineral water and the corresponding plastic bottles. Phthalates were extracted with dichloromethane and re-constituted in cyclohexane prior to GC-MS analysis. When the validated GC-MS method was applied to the quantification of the selected phthalates in the samples, only DBP (up to 0.0675+/-0.0018MUg/mL) and DEHP (up to 1.6848+/-0.1631MUg/mL) were found. Furthermore, we provide specific data about the concentration of DBP and DEHP in bottled water attributable to migration of phthalates from respective plastic bottles. PMID- 26134298 TI - Metabolites characterization of timosaponin AIII in vivo and in vitro by using liquid chromatography-mass spectrometry. AB - Timosaponin AIII, a major saponin found in Anemarrhena asphodeloides Bge., exhibits a wide spectrum of bioactivities. It is believed that it may be further developed into a promising new drug. To better understand the pharmacological activities of the component, the investigation of its in vivo and in vitro metabolism was necessary. In this study, the metabolic profile of timosaponin AIII was investigated using liquid chromatography-mass spectrometric (LC/MS) techniques. Two different types of mass spectrometers-aquadrupole time-of-flight (Q-TOF) mass spectrometer and hybrid quadrupole/linear ion trap (Q-TRAP) mass spectrometer were employed to acquire structural information on timosaponin AIII metabolites. Plasma, bile, urine and feces were collected from rats after a single oral dose of 400mg/kg of water solution. A total of 19 metabolites were detected and tentatively identified based on the mass spectral fragmentation patterns, elution order or confirmed using available reference standard. Two metabolites were detected after incubating with rat liver microsomal. What's more, we isolated sarsasapogenin from the collection of urine samples after timosaponin AIII (5.0g) giving orally to 20 rats at a dose of 150.0mg/kg in an interval of 7 days. The present study provided important information about the metabolism of timosaponin AIII which will be helpful for fully understanding the mechanism of this compound's action. PMID- 26134299 TI - Host Responses and Regulation by NFkappaB Signaling in the Liver and Liver Epithelial Cells Infected with A Novel Tick-borne Bunyavirus. AB - Infection in humans by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus transmitted by ticks, is often associated with pronounced liver damage, especially in fatal cases. Little has been known, however, about how liver cells respond to SFTSV and how the response is regulated. In this study we report that proinflammatory cytokines were induced in liver tissues of C57/BL6 mice infected with SFTSV, which may cause tissue necrosis in mice. Human liver epithelial cells were susceptible to SFTSV and antiviral interferon (IFN) and IFN inducible proteins were induced upon infection. We observed that infection of liver epithelial cells led to significant increases in proinflammatory cytokines and chemokines, including IL-6, RANTES, IP-10, and MIP-3a, which were regulated by NFkappaB signaling, and the activation of NFkappaB signaling during infection promoted viral replication in liver epithelial cells. Viral nonstructural protein NSs was inhibitory to the induction of IFN-beta, but interestingly, NFkappaB activation was enhanced in the presence of NSs. Therefore, NSs plays dual roles in the suppression of antiviral IFN-beta induction as well as the promotion of proinflammatory responses. Our findings provide the first evidence for elucidating host responses and regulation in liver epithelial cells infected by an emerging bunyavirus. PMID- 26134301 TI - Ultrafast photoinduced dynamics of the organolead trihalide perovskite CH3NH3PbI3 on mesoporous TiO2 scaffolds in the 320-920 nm range. AB - We present femtosecond broadband transient absorption experiments for the investigation of the carrier dynamics in the organolead trihalide perovskite CH3NH3PbI3. The perovskite was prepared on a mesoporous TiO2 scaffold either by 1 step deposition from solution or by 2-step methods employing deposition of lead iodide followed by an on-surface reaction with methylammonium iodide. The thin films were characterized by XRD and FTIR chemical mapping. After pumping with an ultrashort laser pulse at 400 or 500 nm, the dynamics were monitored by a broadband supercontinuum reaching from the near IR (920 nm) into the UV. Specifically, the usage of quartz substrates and thin perovskite/TiO2 films enabled us to cover the spectral development down to 320 nm. The charge carrier dynamics were largely independent from the specific route of perovskite preparation: initial ultrafast carrier relaxation steps with time constants tauCC and tauCOP of <0.08, 0.2 and 2.6 ps were assigned to carrier-carrier and carrier optical phonon scattering. Pronounced sub-band-gap absorption was found in the near IR at early times. Transient carrier temperatures were extracted from a Boltzmann fit to the blue wing of the photobleach band in the time range 0.2-700 ps, allowing us to distinguish between the decay of acoustic phonons (tauAP = 50 and >1000 ps) and Auger recombination (tauAR = 9, 75 and 450 ps). Carrier relaxation was accompanied by formation of an absorption band around 550 nm, with a characteristic structure assignable to a transient Stark effect, i.e. a red shift of the perovskite spectrum due to the appearance of a directed electric field in the material and possibly additional influence of lattice heating. We observed a substantial Stokes shift between the relaxed photobleach and photoluminescence bands. Contributions of unreacted PbI2 to the transient absorption features appear to be negligible. PMID- 26134300 TI - The effect of human leukocyte antigen G alleles on human papillomavirus infection and persistence in a cohort of HIV-positive pregnant women from Brazil. AB - Patients with compromised immune systems have more severe intraepithelial lesions and more rapid disease progression, in addition to increased risk for cervical cancer. Persistent infection by the human papillomavirus (HPV) is a necessary step in that process. By inducing expression of inhibitory ligands of natural killer cells, like HLA-G, HPV avoids the elimination of infected cells. Recent studies have investigated polymorphisms in HLA-G that may be associated with susceptibility to HPV infection and persistence. One hundred-forty HIV(+) pregnant women from Brazil had a DNA fragment comprising HLA-G exons 2-4 PCR amplified, cloned, sequenced and analyzed for allele determination. Altogether, 22 alleles comprising 52 different genotypes were found. Four novel HLA-G alleles were characterized. We have not observed association of specific HLA-G alleles with HPV infection, but found a protective effect of the G:01:01:02 allele against the occurrence of intraepithelial lesions. In addition to describing new HLA-G alleles and defining new reference sequences, our data provide a better understanding of the impact of HLA-G alleles on HPV-related disease. PMID- 26134302 TI - Establishment of a highly metastatic model with a newly isolated lung adenocarcinoma cell line. AB - Lung cancer is the leading cause of malignancy-related death worldwide, and metastasis always results in a poor prognosis. However, therapeutic progress is hampered by a deficiency of appropriate pre-clinical metastatic models. To bridge this experimental gap, we developed an in vivo metastatic model via subcutaneous (s.c.) injection. The original cell line (XL-2) adopted in this model was newly isolated from the ascites of a patient with extensive metastases of lung adenocarcinoma, thereby avoiding any alteration of its initial molecular biology features from artificial serial cultivation. After comprehensive phenotypical and histological analysis, it was identified as a lung adenocarcinoma cell line. Additionally, the drug test showed that XL-2 cell line was sensitive to docetaxel, and resistant to doxorubicin, indicating it might serve as a cell line model of drug resistance for identifying mechanisms of tumors resistant to doxorubicin. Through this s.c. model, we further obtained a highly metastatic cell line (designated XL-2sci). The metastatic rate of mice in XL-2 group was 3/10, in contrast to the rate of 9/10 in XL-2sci group. Optical imaging, micro computed tomography (micro-CT) scanning and Transwell assays were further applied to identify the enhanced metastatic capacity of Xl-2sci cells both in vivo and in vitro. Compared with XL-2 cells, ITRAQ labeled proteomics profiling study showed that some tumor metastasis-associated proteins were upregulated in XL-2sci cells, which also indicated the reliability of our model. Proliferation ability of XL-2 and XL-2sci were also evaluated. Results showed that highly metastatic XL-2sci possessed a decreased proliferation capacity versus XL-2, which demonstrated that its increased metastatic activity was not facilitated by a faster growth rate. In conclusion, we successfully developed an in vivo metastatic model using a newly established lung adenocarcinoma cell line, which will be beneficial to further investigations of lung cancer metastasis and to the development of anti metastasis drugs. PMID- 26134303 TI - The effects of modeling contingencies in the treatment of food selectivity in children with autism. AB - The current study investigated the effectiveness of stating and modeling contingencies in increasing food consumption for two children with food selectivity. Results suggested that stating and modeling a differential reinforcement (DR) contingency for food consumption was effective in increasing consumption of two target foods for one child, and stating and modeling a DR plus nonremoval of the spoon contingency was effective in increasing consumption of the remaining food for the first child and all target foods for the second child. PMID- 26134304 TI - Interaction of six protoberberine alkaloids with human organic cation transporters 1, 2 and 3. AB - 1. Organic cation transporters (OCTs) play an important role in drug safety and efficacy. Protoberberine alkaloids are ubiquitous organic cations or weak bases with remarkable biological actives. This study was to elucidate the potential interaction of alkaloids (coptisine, jatrorrhizine, epiberberine, berberrubine, palmatine and corydaline) with OCTs using Madin-Darby canine kidney (MDCK) cells stably expressing human OCT1, OCT2 and OCT3. 2. All the tested alkaloids significantly inhibited the uptake of MPP(+), a model OCT substrate, in MDCK hOCTs cells with the IC50 of 0.931-9.65 MUM. Additionally, coptisine, jatrorrhizine and epiberberine were substrates of all the hOCTs with the Km of 0.273-5.80 MUM, whereas berberrubine was a substrate for hOCT1 and hOCT2, but not for hOCT3, the Km values were 1.27 and 1.66 MUM, respectively. The transport capacity of coptisine in MDCK cells expressing the variants of hOCT1-P341L or hOCT2-A270S was significantly higher than that in wild-type (WT) cells with the Clint (Vmax/Km) of 379 +/- 7.4 and 433 +/- 5.7 MUl/mg protein/min, respectively. 3. The above data indicate that the tested alkaloids are potent inhibitors, and coptisine, jatrorrhizine, epiberberine and berberrubine are substrates of hOCT1, hOCT2 and/or hOCT3 with high affinity. In addition, the variants (OCT1-P341L and OCT2-A270S) possess higher transport capacity to coptisine than WT hOCTs. PMID- 26134305 TI - A limited overlap between intratumoral distribution of 1-(5-fluoro-5-deoxy-alpha D-arabinofuranosyl)-2-nitroimidazole and copper-diacetyl-bis[N(4) methylthiosemicarbazone]. AB - Positron emission tomography (PET) imaging of tumor hypoxia provides valuable information for cancer treatment planning. Two types of PET tracers, nitroimidazole compounds and [62,64Cu] copper-diacetyl-bis[N(4)-methylthio- semicarbazone] (Cu-ATSM), have been used for imaging hypoxic tumors. High accumulation of these tracers in tumors was shown to predict poor prognosis. Both similar and different intratumoral distributions of these PET tracers have been reported with some studies questioning the dependence of the Cu-ATSM accumulation on hypoxia. In the present study, we compared the intratumoral distribution and cellular uptake of 1-(5-fluoro-5-deoxy-alpha-D-arabinofuranosyl)-2-nitroimidazole (FAZA) and Cu-ATSM. Intratumoral distributions of FAZA and Cu-ATSM compared by double tracer autoradiography in xenografts of 8 cancer cell lines and 3 cancer tissue originated spheroids (CTOSs) showed that only a limited overlap was observed between the regions with high levels of FAZA and Cu-ATSM accumulation in all the xenografts. Immunohistochemistry in the regions enriched with FAZA and Cu ATSM in xenografts demonstrated that pimonidazole adducts were in regions that accumulated high levels of FAZA, while HIF-1alpha was in areas enriched with either tracer. In addition, we examined the cellular uptake of FAZA and Cu-ATSM at different levels of oxygen concentration in 4 cell lines and revealed that cellular uptake of FAZA was increased with the decrease of oxygen concentration from 20 to 2 and from 2 to 1%, while the Cu-ATSM uptake increased with the decrease of oxygen concentration from 20 to 2%, but did not increase with the decrease from 2 to 1%. Our findings indicate that intratumoral distributions of FAZA and Cu-ATSM were essentially non-overlapping and although hypoxia affects the buildup of both tracers, the accumulation of Cu-ATSM occurred at milder hypoxia compared to the conditions required for the accumulation of FAZA. Therefore, accumulation levels of FAZA and Cu-ATSM may be considered as independent biomarkers. PMID- 26134306 TI - Magnetic resonance imaging of bilateral split lateral rectus transposition to the medial globe. AB - PURPOSE: Medial transposition of the split or intact lateral rectus (LR) muscle in oculomotor palsy improves extreme exotropia. We studied rectus pulley positions using high-resolution surface coil MRI before and after LR split with medial transposition surgery in a patient with bilateral oculomotor and trochlear nerve palsies. METHODS: This is a report of a 14-year-old girl with 90Delta exotropia due to bilateral oculomotor and trochlear nerve palsies following traumatic midbrain infarction at age 6 years. Surgery comprised longitudinal division of each LR into a superior and inferior, threading of both halves between the inferior rectus (IR) and inferior oblique inferiorly, and inferior to the superior oblique and the superior rectus superiorly, with suturing of each 10 mm posterior to the medial rectus (MR) insertion. RESULTS: Pre-operative MRI of the orbit and extraocular muscles (EOMs) with thin, 2-mm slices revealed bilateral atrophy of all EOMs supplied by the oculomotor and trochlear nerves. Post-operative MRI at 2 months demonstrated no significant changes in rectus EOM pulley positions compared with pre-operative values. CONCLUSIONS: The LR pulley does not change position even after split LR transposition to the MR insertion, confirming the profound constraint of the connective tissue pulley system on the LR path. PMID- 26134307 TI - Histopathologic features of a resolving orbital Langerhans cell histiocytosis. PMID- 26134308 TI - Scorpion Venom Heat-Resistant Peptide Attenuates Glial Fibrillary Acidic Protein Expression via c-Jun/AP-1. AB - Scorpion venom has been used in the Orient to treat central nervous system diseases for many years, and the protein/peptide toxins in Buthus martensii Karsch (BmK) venom are believed to be the effective components. Scorpion venom heat-resistant peptide (SVHRP) is an active component of the scorpion venom extracted from BmK. In a previous study, we found that SVHRP could inhibit the formation of a glial scar, which is characterized by enhanced glial fibrillary acidic protein (GFAP) expression, in the epileptic hippocampus. However, the cellular and molecular mechanisms underlying this process remain to be clarified. The results of the present study indicate that endogenous GFAP expression in primary rat astrocytes was attenuated by SVHRP. We further demonstrate that the suppression of GFAP was primarily mediated by inhibiting both c-Jun expression and its binding with AP-1 DNA binding site and other factors at the GFAP promoter. These results support that SVHRP contributes to reducing GFAP at least in part by decreasing the activity of the transcription factor AP-1. In conclusion, the effects of SVHRP on astrocytes with respect to the c-Jun/AP-1 signaling pathway in vitro provide a practical basis for studying astrocyte activation and inhibition and a scientific basis for further studies of traditional medicine. PMID- 26134309 TI - Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism and Risk of Schizophrenia: A Meta-analysis of Case-Control Studies. AB - According to evidences from previous family and association studies, it has been claimed that genetic factors are involved in the neuropathogenesis of Schizophrenia disorder. Whether the Val66Met variant of brain-derived neurotrophic factor (BDNF) gene plays any roles in the pathogenesis of this syndrome or could be a potential biomarker for prognosis of this disorder has been a long-standing controversial issue. We performed a meta-analysis restricted to case-control studies and searched Pubmed, PsychInfo, and Google scholar using keywords including 'association,' 'Val66Met,' 'BDNF,' and 'schizophrenia' published up to May 1, 2015. A total of 39 studies for schizophrenia were combined by fixed- and random-effects models. The pooled results from the schizophrenia sample indicated no significant evidence for the association of Val/Val and Val/Met genotypes of BDNF gene with schizophrenia, but it was observed that there is an association between Met/Met polymorphism and schizophrenia in Asian, European, and Chinese populations, this means that the risk of schizophrenia in Asian, European, and Chinese populations with Met/Met genotype is, respectively, 9, 26, and 9%. There was a significant association between BDNF Val66Met polymorphism and schizophrenia in our meta-analysis study. We cannot rule out the possibility that other polymorphisms in the BDNF gene are involved in the pathophysiology of schizophrenia. In addition, more studies should be conducted on the polymorphisms in other genes to elucidate their possible roles in schizophrenia. PMID- 26134310 TI - Protocatechuic Acid Inhibits Inflammatory Responses in LPS-Stimulated BV2 Microglia via NF-kappaB and MAPKs Signaling Pathways. AB - Protocatechuic acid (PA), a major metabolite of anthocyanins, has been reported to possess antioxidant and anti-inflammatory activities. However, the effects of PA on LPS-induced inflammatory responses in microglia have not been reported. The aim of this study was to investigate the anti-inflammatory effects and molecular mechanisms of PA on LPS-stimulated BV2 microglia. The production of inflammatory mediators TNF-alpha, IL-6, IL-1beta, and PGE2 were detected by ELISA. TLR4, NF kappaB and MAPKs activation were detected by western blotting. Our results demonstrated that PA dose-dependently inhibited LPS-induced TNF-alpha, IL-6, IL 1beta, and PGE2 production. In addition, PA suppressed LPS-induced TLR4 expression, NF-kappaB and MAPKs activation, which resulted in the inhibition of inflammatory mediators. In conclusion, these results suggested that PA exhibited anti-inflammatory effects on LPS-stimulated BV2 microglia and the mechanisms were involved in the inhibition of TLR4-mediated NF-kappaB and MAPKs signaling pathways. PMID- 26134311 TI - Dendritic nanoconjugates for intracellular delivery of neutral oligonucleotides. AB - Dendrimer-based gene delivery has been constrained by intrinsic toxicity and suboptimal nanostructure. Conjugation of neutral morpholino oligonucleotides (ONs) with PAMAM dendrimers resulted in neutral, uniform, and ultra-small (~10 nm) nanoconjugates. The nanoconjugates dramatically enhanced cellular delivery of the ONs in cancer cells. After release from the dendrimer in the cytosol, the ONs produced potent functional activity without causing significant cytotoxicity. When carrying an apoptosis-promoting ON, the nanoconjugates produced cancer cell killing directly. Thus, the dendritic nanoconjugates may provide an effective tool for delivering ONs to tumors and other diseased tissues. PMID- 26134312 TI - microRNAs as Developmental Regulators. AB - The field of miRNA biology is relatively young, but its impact on our understanding of the regulation of a wide array of cell functions is far reaching. The importance of miRNAs in development has become nearly ubiquitous, with miRNAs contributing to development of most cells and organs. Although miRNAs are clearly interwoven into known regulatory networks that control cell development, the specific modalities by which they intersect are often quite distinct and cleverly achieved. The frequently emerging theme of feed-back and feed-forward loops to either counterbalance or reinforce the gene programs that they influence is a common thread. Many of these examples of miRNAs as developmental regulators are presently found in organs with different miRNAs and targets, whereas novel, unexpected themes emerge in the context of mouse development as we learn more about this rapidly developing area of biology. PMID- 26134314 TI - Mechanisms and Evidence of Genital Coevolution: The Roles of Natural Selection, Mate Choice, and Sexual Conflict. AB - Genital coevolution between the sexes is expected to be common because of the direct interaction between male and female genitalia during copulation. Here we review the diverse mechanisms of genital coevolution that include natural selection, female mate choice, male-male competition, and how their interactions generate sexual conflict that can lead to sexually antagonistic coevolution. Natural selection on genital morphology will result in size coevolution to allow for copulation to be mechanically possible, even as other features of genitalia may reflect the action of other mechanisms of selection. Genital coevolution is explicitly predicted by at least three mechanisms of genital evolution: lock and key to prevent hybridization, female choice, and sexual conflict. Although some good examples exist in support of each of these mechanisms, more data on quantitative female genital variation and studies of functional morphology during copulation are needed to understand more general patterns. A combination of different approaches is required to continue to advance our understanding of genital coevolution. Knowledge of the ecology and behavior of the studied species combined with functional morphology, quantitative morphological tools, experimental manipulation, and experimental evolution have been provided in the best-studied species, all of which are invertebrates. Therefore, attention to vertebrates in any of these areas is badly needed. PMID- 26134315 TI - Paleobiological Perspectives on Early Microbial Evolution. AB - Microfossils, stromatolites, and chemical biosignatures indicate that Earth became a biological planet more than 3.5 billion years ago, making most of life's history microbial. Proterozoic rocks preserve a rich record of cyanobacteria, including derived forms that differentiate multiple cell types. Stromatolites, in turn, show that microbial communities covered the seafloor from tidal flats to the base of the photic zone. The Archean record is more challenging to interpret, particularly on the question of cyanobacterial antiquity, which remains to be resolved. In the late Neoproterozoic Era, increasing oxygen and radiating eukaryotes altered the biosphere, with planktonic algae gaining ecological prominence in the water column, whereas seaweeds and, eventually, animals spread across shallow seafloors. From a microbial perspective, however, animals, algae, and, later, plants simply provided new opportunities for diversification, and, to this day, microbial metabolisms remain the only essential components of biogeochemical cycles. PMID- 26134313 TI - Emergent Properties of the Metaphase Spindle. AB - A metaphase spindle is a complex structure consisting of microtubules and a myriad of different proteins that modulate microtubule dynamics together with chromatin and kinetochores. A decade ago, a full description of spindle formation and function seemed a lofty goal. Here, we describe how work in the last 10 years combining cataloging of spindle components, the characterization of their biochemical activities using single-molecule techniques, and theory have advanced our knowledge. Taken together, these advances suggest that a full understanding of spindle assembly and function may soon be possible. PMID- 26134316 TI - The Origin of Mutants Under Selection: How Natural Selection Mimics Mutagenesis (Adaptive Mutation). AB - Selection detects mutants but does not cause mutations. Contrary to this dictum, Cairns and Foster plated a leaky lac mutant of Escherichia coli on lactose medium and saw revertant (Lac(+)) colonies accumulate with time above a nongrowing lawn. This result suggested that bacteria might mutagenize their own genome when growth is blocked. However, this conclusion is suspect in the light of recent evidence that revertant colonies are initiated by preexisting cells with multiple copies the conjugative F'lac plasmid, which carries the lac mutation. Some plated cells have multiple copies of the simple F'lac plasmid. This provides sufficient LacZ activity to support plasmid replication but not cell division. In nongrowing cells, repeated plasmid replication increases the likelihood of a reversion event. Reversion to lac(+) triggers exponential cell growth leading to a stable Lac(+) revertant colony. In 10% of these plated cells, the high-copy plasmid includes an internal tandem lac duplication, which provides even more LacZ activity-sufficient to support slow growth and formation of an unstable Lac(+) colony. Cells with multiple copies of the F'lac plasmid have an increased mutation rate, because the plasmid encodes the error-prone (mutagenic) DNA polymerase, DinB. Without DinB, unstable and stable Lac(+) revertant types form in equal numbers and both types arise with no mutagenesis. Amplification and selection are central to behavior of the Cairns-Foster system, whereas mutagenesis is a system-specific side effect or artifact caused by coamplification of dinB with lac. Study of this system has revealed several broadly applicable principles. In all populations, gene duplications are frequent stable genetic polymorphisms, common near-neutral mutant alleles can gain a positive phenotype when amplified under selection, and natural selection can operate without cell division when variability is generated by overreplication of local genome subregions. PMID- 26134318 TI - Adult Neurogenesis in Humans. AB - Adult neurogenesis appears very well conserved among mammals. It was, however, not until recently that quantitative data on the extent of this process became available in humans, largely because of methodological challenges to study this process in man. There is substantial hippocampal neurogenesis in adult humans, but humans appear unique among mammals in that there is no detectable olfactory bulb neurogenesis but continuous addition of new neurons in the striatum. PMID- 26134319 TI - Nuclear DNA Content Varies with Cell Size across Human Cell Types. AB - Variation in the size of cells, and the DNA they contain, is a basic feature of multicellular organisms that affects countless aspects of their structure and function. Within humans, cell size is known to vary by several orders of magnitude, and differences in nuclear DNA content among cells have been frequently observed. Using published data, here we describe how the quantity of nuclear DNA across 19 different human cell types increases with cell volume. This observed increase is similar to intraspecific relationships between DNA content and cell volume in other species, and interspecific relationships between diploid genome size and cell volume. Thus, we speculate that the quantity of nuclear DNA content in somatic cells of humans is perhaps best viewed as a distribution of values that reflects cell size distributions, rather than as a single, immutable quantity. PMID- 26134317 TI - Epigenetic Regulation of Chromatin States in Schizosaccharomyces pombe. AB - This article discusses the advances made in epigenetic research using the model organism fission yeast Schizosaccharomyces pombe. S. pombe has been used for epigenetic research since the discovery of position effect variegation (PEV). This is a phenomenon in which a transgene inserted within heterochromatin is variably expressed, but can be stably inherited in subsequent cell generations. PEV occurs at centromeres, telomeres, ribosomal DNA (rDNA) loci, and mating-type regions of S. pombe chromosomes. Heterochromatin assembly in these regions requires enzymes that modify histones and the RNA interference (RNAi) machinery. One of the key histone-modifying enzymes is the lysine methyltransferase Clr4, which methylates histone H3 on lysine 9 (H3K9), a classic hallmark of heterochromatin. The kinetochore is assembled on specialized chromatin in which histone H3 is replaced by the variant CENP-A. Studies in fission yeast have contributed to our understanding of the establishment and maintenance of CENP-A chromatin and the epigenetic activation and inactivation of centromeres. PMID- 26134320 TI - Molecular Genetic Strategies in the Study of Corticohippocampal Circuits. AB - The first reproductively viable genetically modified mice were created in 1982 by Richard Palmiter and Ralph Brinster (Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM. 1982. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300: 611-615). In the subsequent 30 plus years, numerous ground breaking technical advancements in genetic manipulation have paved the way for improved spatially and temporally targeted research. Molecular genetic studies have been especially useful for probing the molecules and circuits underlying how organisms learn and remember-one of the most interesting and intensively investigated questions in neuroscience research. Here, we discuss selected genetic tools, focusing on corticohippocampal circuits and their implications for understanding learning and memory. PMID- 26134323 TI - What motivates use of community-based human immunodeficiency virus testing in rural South Africa? AB - Despite substantial progress in implementing HIV testing, challenges remain in achieving widespread uptake particularly in rural resource-limited settings. We sought to understand motivations for HIV testing in a community-based HIV testing programme in rural South Africa. We conducted a questionnaire survey in participants undergoing voluntary HIV testing within an ongoing community-based integrated HIV/tuberculosis intensive case finding programme at congregate rural settings. Participants responded to a six-item non-mutually exclusive motivations survey which included the topics of feeling ill, recent HIV exposure, risky lifestyle, illness in a family member, and pregnancy. Among 2068 respondents completing the survey, 1393 (67.4%) were women, median age was 40 years (IQR 19 56), and 1235 (59.7%) were first-time testers. Among all testers, 142 (6.9%) were HIV-positive with median CD4 count was 346 cells/mm(3) (IQR 218-542). Community based testing for HIV is acceptable and meets the needs of community members in rural South Africa. Motivations for HIV testing at the community level are complex and differ according to gender, age, site of community testing, and HIV status. These differences can be utilised to improve the focus and yield of community-based HIV screening. PMID- 26134324 TI - The role of Clinical Trial Units in investigator- and industry-initiated research projects. AB - Six multidisciplinary competence centres (Clinical Trial Units, CTUs) in Basel, Berne, Geneva, Lausanne, St. Gallen and Zurich provide professional support to clinical researchers in the planning, implementation, conduct and evaluation of clinical studies. Through their coordinated network, these units promote high quality, nationally harmonised and internationally standardised clinical research conduct in Switzerland. We will describe why this network has been established, how it has been successful in stilling the growing need for clinical research support, which training and education opportunities it offers, and how it created national awareness for the still-existing hurdles towards clinical research excellence in Switzerland. Taking the CTU Basel as an example, we show that a considerable number (25%) of the studies submitted for regulatory approval in 2013 were supported by the CTU, decreasing the number of findings in ethics reviews by about one-third. We conclude that these achievements, together with a Swiss national funding model for clinical research, and improved national coordination, will be critical factors to successfully position Swiss clinical research at the international forefront. PMID- 26134325 TI - Moral Distress, Moral Courage. PMID- 26134322 TI - Identification of Chemical Inhibitors of beta-Catenin-Driven Liver Tumorigenesis in Zebrafish. AB - Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. The search for targeted treatments has been hampered by the lack of relevant animal models for the genetically diverse subsets of HCC, including the 20-40% of HCCs that are defined by activating mutations in the gene encoding beta-catenin. To address this chemotherapeutic challenge, we created and characterized transgenic zebrafish expressing hepatocyte-specific activated beta-catenin. By 2 months post fertilization (mpf), 33% of transgenic zebrafish developed HCC in their livers, and 78% and 80% of transgenic zebrafish showed HCC at 6 and 12 mpf, respectively. As expected for a malignant process, transgenic zebrafish showed significantly decreased mean adult survival compared to non-transgenic control siblings. Using this novel transgenic model, we screened for druggable pathways that mediate beta catenin-induced liver growth and identified two c-Jun N-terminal kinase (JNK) inhibitors and two antidepressants (one tricyclic antidepressant, amitriptyline, and one selective serotonin reuptake inhibitor) that suppressed this phenotype. We further found that activated beta-catenin was associated with JNK pathway hyperactivation in zebrafish and in human HCC. In zebrafish larvae, JNK inhibition decreased liver size specifically in the presence of activated beta catenin. The beta-catenin-specific growth-inhibitory effect of targeting JNK was conserved in human liver cancer cells. Our other class of hits, antidepressants, has been used in patient treatment for decades, raising the exciting possibility that these drugs could potentially be repurposed for cancer treatment. In support of this proposal, we found that amitriptyline decreased tumor burden in a mouse HCC model. Our studies implicate JNK inhibitors and antidepressants as potential therapeutics for beta-catenin-induced liver tumors. PMID- 26134327 TI - Research at the Bedside: It Makes A Difference. AB - Research at the bedside makes a difference for our patients, and also for our nurses. However, it is now time to broaden our focus from research on interventions or events at a narrow point in time to research that addresses care across the continuum. This continuum may start at the point of injury, such as the battlefield through en route care delivered during the 8000-mile journey home for our wounded warriors, or for critically ill patients as they move between the emergency department, operating room, and intensive care unit. This focus also requires researchers to consider "care within context," that is, research- and evidence-based practice tailored to the unique conditions of the care environment. Beyond conducting research and developing new knowledge is the challenge of translating evidence into practice. A culture of inquiry is a critical element in the successful translation of evidence into practice. In a culture of inquiry, nurses are encouraged to question and evaluate their practice, provide evidence-based care, and actively participate in and lead clinical inquiry. This article draws from a program of applied clinical research reflecting care across the continuum within both military and civilian health care settings and discusses how the application of these research findings and the advancement of a culture of inquiry make a difference for both patients and nurses. PMID- 26134328 TI - Testing the Feasibility of Skype and FaceTime Updates With Parents in the Neonatal Intensive Care Unit. AB - BACKGROUND: Effective provider-parent relationships are essential during critical illness when treatment decisions are complex, the environment is crowded and unfamiliar, and outcomes are uncertain. OBJECTIVES: To evaluate the feasibility of daily Skype or FaceTime updates with parents of patients in the neonatal intensive care unit (NICU) and to assess the intervention's potential for improving parent-provider relationships. METHODS: A pre/post mixed-methods approach was used. NICU parent participants received daily Skype or FaceTime updates for 5 days and completed demographic and feasibility surveys. Parents also completed Penticuff's Parents' Understanding survey before and after the intervention. Nurses and physicians completed feasibility surveys after each update. RESULTS: Twenty-six parents were enrolled and 15 completed the study. More than 90% of providers and parents perceived the intervention to be reliable and easy to use, and about 80% of parents and providers rated video and audio quality as either excellent or good. Frozen screens and missed updates due to scheduling problems were challenges. Two of the 4 subscores on the Parents' Understanding survey improved significantly. Qualitative data favor the intervention as meaningful for parents. CONCLUSIONS: Real-time videoconferencing via Skype or FaceTime is feasible for providing updates for parents when they cannot be present in the NICU and can be used to include parents in bedside rounds. Videoconferencing updates may improve relationships between parents and the health care team. PMID- 26134321 TI - Structural Components of Synaptic Plasticity and Memory Consolidation. AB - Consolidation of implicit memory in the invertebrate Aplysia and explicit memory in the mammalian hippocampus are associated with remodeling and growth of preexisting synapses and the formation of new synapses. Here, we compare and contrast structural components of the synaptic plasticity that underlies these two distinct forms of memory. In both cases, the structural changes involve time dependent processes. Thus, some modifications are transient and may contribute to early formative stages of long-term memory, whereas others are more stable, longer lasting, and likely to confer persistence to memory storage. In addition, we explore the possibility that trans-synaptic signaling mechanisms governing de novo synapse formation during development can be reused in the adult for the purposes of structural synaptic plasticity and memory storage. Finally, we discuss how these mechanisms set in motion structural rearrangements that prepare a synapse to strengthen the same memory and, perhaps, to allow it to take part in other memories as a basis for understanding how their anatomical representation results in the enhanced expression and storage of memories in the brain. PMID- 26134329 TI - Complexity Assessment and Monitoring to Ensure Optimal Outcomes Tool for Measuring Pediatric Critical Care Nursing. AB - BACKGROUND: Historically, nursing productivity has been measured in adult settings and based on time, intensity, and resource allocation. OBJECTIVE: To develop a comprehensive measure of pediatric critical care nursing workload. METHODS: An expert panel of pediatric critical care nurses used a modified Delphi method to identify 14 domains of nursing care with a number of corresponding care items in each domain. By consensus, they assigned each care item a cognitive complexity rating from 1 to 5. The panel next developed a classification system (classes I-V) to support interpretation of the patient's total score. The Complexity Assessment and Monitoring to Ensure Optimal Outcomes (CAMEO) tool was initiated with a cohort of 75 pediatric cardiac critical care patients to verify comprehensive capture of nursing care. Results of completed CAMEO tools were summarized by using descriptive statistics. RESULTS: The cognitive workload across 14 domains of care was described, and each care item in the domain was scored. The range of CAMEO total scores was 25 to 230 (median, 124). For the initial cohort of patients, the cognitive complexity of care classifications were 13% as class I or II, 80% as class III or IV, and 7% as class V. CONCLUSIONS: The CAMEO tool was comprehensive in describing and quantifying the cognitive workload of pediatric critical care nurses. The CAMEO classification process informs staffing needs that support synergy between the needs of patients and their families and nurses' knowledge and skill. Articulation of nursing care focused on informed clinical decision making is needed to justify the value of skilled nurses. PMID- 26134330 TI - Influence of Institutional Guidelines on Oral Hygiene Practices in Intensive Care Units. AB - BACKGROUND: Maintaining oral hygiene is a key component of preventing ventilator associated pneumonia; however, practices are inconsistent. OBJECTIVES: To explore how characteristics of institutional guidelines for oral hygiene influence nurses' oral hygiene practices and perceptions of that practice. METHODS: Oral hygiene section of a larger survey study on prevention of ventilator-associated pneumonia. Critical care nurses at 8 hospitals in Northern California that had more than 1000 ventilator days in 2009 were recruited to participate in the survey. Twenty-one questions addressed oral hygiene practices and practice perceptions. Descriptive statistics, analysis of variance, and Spearman correlations were used for analyses. RESULTS: A total of 576 critical care nurses (45% response rate) responded to the survey. Three types of institutional oral hygiene guidelines existed: nursing policy, order set, and information bulletin. Nursing policy provided the most detail about the oral hygiene care; however, adherence, awareness, and priority level were higher with order sets (P < .05). The content and method of disseminating these guidelines varied, and nursing practices were affected by these differences. Nurses assessed the oral cavity and used oral swabs more often when those practices were included in institutional guidelines. CONCLUSIONS: The content and dissemination method of institutional guidelines on oral hygiene do influence the oral hygiene practices of critical care nurses. Future studies examining how institutional guidelines could best be incorporated into routine workflow are needed. PMID- 26134331 TI - Clinical Indicators for Endotracheal Suctioning in Adult Patients Receiving Mechanical Ventilation. AB - BACKGROUND: Critically ill patients who need mechanical ventilation require endotracheal suctioning. Guidelines recommend coarse crackles over the trachea and/or the presence of a sawtooth pattern on the flow-volume loop of the ventilator waveform as the best indicators. OBJECTIVE: To determine clinical cues for endotracheal suctioning in patients who require mechanical ventilation. METHODS: A descriptive study of 42 adult patients receiving mechanical ventilation. After baseline endotracheal suctioning with a closed-system device, patients were assessed hourly up to 4 hours for guideline-based cues for endotracheal suctioning and lung sounds were auscultated. Endotracheal suctioning was done when cues were detected or 4 hours after baseline suctioning. Secretions were collected, measured, and weighed. RESULTS: Most patients were male (62%) and white (93%). Mean age was 51 years, and mean duration of mechanical ventilation was 7.5 days. The median time to endotracheal suctioning was 2 hours, and a mean of 4.4 mL of secretions was removed. Three patients had no cues identified but had 1.0 mL or more of secretions. The most frequent cues were crackles over the trachea (88%), sawtooth waveform (33%), coughing (29%), and visible secretions (5%). Cues resolved and physiological parameters improved after suctioning. Coarse lung sounds did not improve. CONCLUSIONS: Patients receiving mechanical ventilation should be routinely assessed for coarse crackles over the trachea, the most common indicator for endotracheal suctioning. Despite common practice, assessment of lung sounds to identify the need for suctioning is not supported. PMID- 26134332 TI - Using Endotracheal Suctioning For Patients. PMID- 26134333 TI - Scoring Systems for Outcome Prediction in a Cardiac Surgical Intensive Care Unit: A Comparative Study. AB - BACKGROUND: Most scoring systems used to predict clinical outcome in critical care were not designed for application in cardiac surgery patients. OBJECTIVES: To compare the predictive ability of the most widely used scoring systems (Acute Physiology and Chronic Health Evaluation [APACHE] II, Simplified Acute Physiology Score [SAPS] II, and Sequential Organ Failure Assessment [SOFA]) and of 2 specialized systems (European System for Cardiac Operative Risk Evaluation [EuroSCORE] II and the cardiac surgery score [CASUS]) for clinical outcome in patients after cardiac surgery. METHODS: Consecutive patients admitted to a cardiac surgical intensive care unit (CSICU) were prospectively studied. Data on the preoperative condition, intraoperative parameters, and postoperative course were collected. EuroSCORE II, CASUS, and scores from 3 general severity-scoring systems (APACHE II, SAPS II, and SOFA) were calculated on the first postoperative day. Clinical outcome was defined as 30-day mortality and in-hospital morbidity. RESULTS: A total of 150 patients were included. Thirty-day mortality was 6%. CASUS was superior in outcome prediction, both in relation to discrimination (area under curve, 0.89) and calibration (Brier score = 0.043, chi(2) = 2.2, P = .89), followed by EuroSCORE II for 30-day mortality (area under curve, 0.87) and SOFA for morbidity (Spearman rho= 0.37 and 0.35 for the CSICU length of stay and duration of mechanical ventilation, respectively; Wilcoxon W = 367.5, P = .03 for probability of readmission to CSICU). CONCLUSIONS: CASUS can be recommended as the most reliable and beneficial option for benchmarking and risk stratification in cardiac surgery patients. PMID- 26134334 TI - Atrial Fibrillation and Mortality in Critically Ill Patients: A Retrospective Study. AB - BACKGROUND: Although atrial fibrillation is common in critically ill patients, no large studies on its impact on patient mortality in general intensive care units have been done. OBJECTIVE: To evaluate the association between atrial fibrillation and hospital mortality in critically ill patients. METHODS: In a retrospective cohort study, critically ill patients who had atrial fibrillation during a 2-year period were compared with patients who did not. The primary outcome was death during the hospital stay. Secondary outcomes were duration of mechanical ventilation and lengths of stay in the intensive care unit and hospital. RESULTS: Among a total of 2018 first-time admissions to the intensive care unit during the study period, 421 patients (20.9%) had atrial fibrillation. Patients with atrial fibrillation had higher mortality, significantly longer duration of mechanical ventilation, and longer stays in the intensive care unit and in the hospital than did patients without this cardiac arrhythmia. However, multiple logistic regression analysis indicated that atrial fibrillation was not independently associated with a higher risk for death. CONCLUSION: Atrial fibrillation may not be independently associated with hospital mortality. PMID- 26134335 TI - Factors Associated With Occipital Pressure Ulcers in Hospitalized Infants and Children. AB - BACKGROUND: The occiput is a common location for development of pressure ulcers in hospitalized infants and young children. However, risk factors associated with occurrence of the ulcers have not been fully described. OBJECTIVE: To identify factors associated with development of occipital pressure ulcers in acutely ill infants and children. METHODS: Charts of all patients with occipital pressure ulcers reported in a computerized safety event reporting system since its implementation in 2005 and of any patients with such ulcers recalled by members of the skin care special interest group were reviewed retrospectively. RESULTS: During a 4-year period, 60 cases of occipital pressure ulcers were identified: 40% stage I, 12% stage II, 30% unstageable, and 18% deep tissue Injury. The median age of the sample was 12 months. Among the patients, 86% were in the intensive care unit with cardiovascular or pulmonary problems. A total of 68% had comorbid conditions. Most of the patients were less than 1 year old; were critically ill, requiring high-risk therapies; and had multiple medical devices in place. Patients with the ulcers were commonly treated with mechanical ventilation (83%) and sedation (74%) and were described as agitated (42%). Many of these patients were receiving vasoactive medications (50%) and had vascular access devices in the neck that restricted head movement (45%). When documented, the median Braden Q score was 16. CONCLUSIONS: Infants and children at risk for occipital pressure ulcers can be prospectively identified, allowing implementation of nursing interventions to prevent these ulcers. PMID- 26134336 TI - Pressure Ulcer Incidence in Patients Wearing Nasal-Oral Versus Full-Face Noninvasive Ventilation Masks. AB - BACKGROUND: Device-related pressure ulcers from noninvasive ventilation masks alter skin integrity and cause patients discomfort. OBJECTIVE: To examine the incidence, location, and stage of pressure ulcers and patients' comfort with a nasal-oral mask compared with a full-face mask. METHODS: A before-after study of a convenience sample of patients with noninvasive ventilation orders in 5 intensive care units was conducted. Two groups of 100 patients each received either the nasal-oral mask or the full-face mask. Skin was assessed before the mask was applied and every 12 hours after that or upon mask removal. Comfort levels were assessed every 12 hours on a Likert scale of 1 to 5 (1, most comfortable). RESULTS: A pressure ulcer developed in 20% of patients in the nasal oral mask group and 2% of patients in the full-face mask group (P < .001). Comfort scores were significantly lower (more comfortable) with the full-face mask (mean [SD], 1.9 [1.1]) than with the nasal-oral mask (mean [SD], 2.7 [1.2], P < .001). Neither mean hours worn nor percentage adherence differed significantly: 28.9 (SD, 27.2) hours and 92% for full-face mask and 25 (SD, 20.7) and 92% for nasal-oral mask. No patients who had a pressure ulcer develop with the nasal-oral mask had a pressure ulcer develop with the full-face mask. CONCLUSION: The full-face mask resulted in significantly fewer pressure ulcers and was more comfortable for patients. The full-face mask is a reasonable alternative to traditional nasal-oral masks for patients receiving noninvasive ventilation. PMID- 26134337 TI - Telemetry Monitoring: Are Admission Criteria Based on Evidence? PMID- 26134338 TI - Drug Induced ECG Abnormalities. PMID- 26134339 TI - Defining the Medical Intensive Care Unit in the Words of Patients and Their Family Members: A Freelisting Analysis. AB - BACKGROUND: No validated conceptual framework exists for understanding the outcomes of patient- and family-centered care in critical care. OBJECTIVE: To explore the meaning of intensive care unit among patients and their families by using freelisting. METHODS: The phrase intensive care unit was used to prompt freelisting among intensive care unit patients and patients' family members. Freelisting is an anthropological technique in which individuals define a domain by listing all words that come to mind in response to a topic. Salience scores, derived from the frequency with which a word was mentioned, the order in which it was mentioned, and the length of each list, were calculated and analyzed. RESULTS: Among the 45 participants, many words were salient to both patients and patients' family members. Words salient solely for patients included consciousness, getting better, noisy, and personal care. Words salient solely for family members included sadness, busy, professional, and hope. The words suffering, busy, and team were salient solely for family members of patients who lived, whereas sadness, professionals, and hope were salient solely for family members of patients who died. The words caring and death were salient for both groups. CONCLUSIONS: Intensive care unit patients and their families define intensive care unit by using words to describe sickness, caring, medical staff, emotional states, and physical qualities of the unit. The results validate the importance of these topics among patients and their families in the intensive care unit and illustrate the usefulness of freelisting in critical care research. PMID- 26134340 TI - Communicating with Patients' Families and Physicians About Prognosis and Goals of Care. AB - BACKGROUND: Integrating palliative care into intensive care requires active involvement of bedside nurses in discussions of patients' prognosis and goals of care. OBJECTIVE: To improve critical care nurses' skills and confidence to engage in discussions with patients' families and physicians about prognosis and goals of care by using a focused educational intervention. METHODS: An 8-hour-long workshop was developed for critical care nurses. Key roles and skills of nurses in communication about prognosis and goals of care were defined. Participants practiced skills during facilitated role-plays. A reflection session addressed burnout, distress, and self-care. Participants completed surveys before, immediately after, and 3 months after their workshop, rating their confidence and skill in performing key tasks. Use of a participant focus group and open-response items in the surveys further elucidated the impact of the workshop. RESULTS: Between March 2011 and April 2013, a total of 82 critical care nurses completed a workshop. Compared with before the workshop, after the workshop, nurses reported greater skill and confidence for 14 survey items (P < .001), including assessing families' understanding of prognosis and goals of care, addressing families' emotional needs, and contributing to family meetings. Increases were sustained 3 months after the workshop. CONCLUSION: Defining roles and providing opportunities for skills practice and reflection can enhance nurses' confidence to engage in discussions about prognosis and goals of care. PMID- 26134341 TI - Cerebral Perfusion Pressure and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Whether delayed cerebral ischemia (DCI) mediates the relationship between Hunt and Hess grade and outcomes after aneurysmal subarachnoid hemorrhage remains unknown. OBJECTIVES: To investigate the relationship between cerebral perfusion pressure, DCI, Hunt and Hess grade, and outcomes after aneurysmal subarachnoid hemorrhage. METHODS: DCI was defined as neurological deterioration due to impaired cerebral blood flow. Relationships between minimum cerebral perfusion pressure and onset and occurrence of DCI were tested by using logistic regression and the accelerated failure time model. The mediation effect of DCI on relationships between Hunt and Hess grade and outcomes was tested by using the bootstrap confidence interval. Outcomes at 3 and 12 months included mortality and neuropsychological, functional, and physical outcomes. RESULTS: DCI occurred in 211 patients (42%). About one-third of the patients had poor functional outcome at 3 (32%) and 12 (30%) months. Impaired neuropsychological outcome was observed in 33% of patients at 3 months and 17% at 12 months. For every increase of 10 mm Hg in cerebral perfusion pressure, odds for DCI increased by 2.78 (95% CI, 2.00 3.87). High perfusion pressure was associated with earlier onset of DCI (P < .001). CONCLUSIONS: DCI does not mediate the relationship of Hunt and Hess grade to functional outcome or death. The relationship between cerebral perfusion pressure and DCI was most likely due to induced hypertension and hypervolemia. Clinical guidelines may need to include limits for induced hypertension. PMID- 26134342 TI - Lack of consistency in the relationship between asymptomatic DVT detected by venography and symptomatic VTE in thromboprophylaxis trials. AB - Asymptomatic deep-vein thrombosis (DVT) detected by mandatory venography, a surrogate outcome, comprises most of the efficacy outcome events in recent thromboprophylaxis trials. The validity of this surrogate to estimate trade-off between thrombotic and bleeding events in these clinical trials requires a consistent relationship between asymptomatic DVT and symptomatic venous thromboembolism (VTE). In this systematic review of high quality VTE prevention trials, we examined the consistency of the ratios of asymptomatic DVT to symptomatic VTE across a broad range of indications. Studies were identified from citations listed in the chapters on VTE prevention in the antithrombotic guidelines by the American College of Chest Physicians, 2012. A study was eligible if it: 1) was a randomised trial comparing an anticoagulant with standard of care; 2) included at least 500 participants; 3) reported asymptomatic or all DVT rates; and 4) reported symptomatic VTE rates. Of the 26 eligible trials, 19 trials were conducted in orthopaedic patients, five in general surgery patients and two in general medical patients. The overall median rates (ranges) for asymptomatic DVT and symptomatic VTE were 9.11 % (0.75 to 54.87 %) and 0.49 % (0.00 to 3.10 %), respectively. The median ratio was 14.53, with a wide range (2.75 to 103.86). Wide variability in the ratios persisted despite indication- and anticoagulant-specific analyses. In VTE prevention trials of alternative anticoagulants, the wide variability in the ratios of asymptomatic DVT to symptomatic VTE precludes judging the trade-off between thrombotic and bleeding events on the basis of composite outcomes dominated by venographic DVT. PMID- 26134343 TI - The complete chloroplast genome sequence of Spathiphyllum kochii. AB - The complete chloroplast sequence of the Spathiphyllum kochii is 163 368 bp in length, containing a pair of inverted repeats of 25 270 bp separated by a large single-copy region and a small single-copy region of 90 482 bp and 22 346 bp, respectively. The chloroplast genome encodes 133 predicted functional genes, including 88 protein-coding genes, four ribosomal RNA genes and 37 transfer RNA genes, 18 of which are duplicated in the inverted repeat regions. The cpDNA is GC rich (37.6%). The chloroplast genome of S. kochii reported here will lay basis for identification, utilization and protection of its germplasm resources. PMID- 26134344 TI - Corrigendum. PMID- 26134345 TI - The mitochondrial genome of Tenthredo tienmushana (Takeuchi) and a related phylogenetic analysis of the sawflies (Insecta: Hymenoptera). AB - The mitochondrial genome sequence of Tenthredo tienmushana (Takeuchi, 1940) (Hymenoptera: Tenthredinidae) (GenBank accession KR703581) was reported. The length of the sequenced region of this mitochondrial genome is 14,943 bp, with 13 protein-coding, two rRNA, 19 tRNA (the trnI, trnQ, and trnM were failed to sequence) genes and a partial A + T-rich region. As in most other sequenced mitochondrial genomes of the suborder "Symphyta", there is no gene rearrangement in the sequenced region compared with the pupative ancestral gene arrangement of insects. All protein-coding genes start with ATN codons. Eleven, one, and one protein-coding genes stop with termination codon TAA, TA, and T, respectively. Phylogenetic analysis using the Bayesian method based on all codon positions of the 13 protein-coding genes supports the monophyly of Tenthredinoidea. Two families of the Tenthredinoidea, i.e. Tenthredinidae and Pergidae, form the basal lineage of the Hymenoptera. Within the Tenthredinidae, the subfamily Tenthrediniinae and Allantinae form a sister lineage and then sister to the Nematinae. The Orussidae was recovered to be a sister group to the Apocrita, which contains Ichneumonidae and Vespidae in our analysis. The Cephoidea is sister to the lineage of Orussoidea + Apocrita. PMID- 26134346 TI - Exploring attitudes toward eating disorders among elite athlete support personnel. AB - To date, little is known about the beliefs, attitudes, and experiences of athlete support personnel (ASP) working in elite sport toward disordered eating (DE) and eating disorders (EDs). This study seeks to explore this area of mental health, employing an attribution model of stigma as a conceptual lens. Interviews were undertaken with 14 service providers (seven males and seven females) working in high-performance sport in Ireland. In contrast to previous research in the general population, findings revealed that sport-based personnel, in the main, did not hold the individual responsible for the development of their eating disorder. The predominant emotional response of those who had worked with an athlete with a known or suspected eating disorder was anxiety and worry. In line with the findings of previous studies with other health professionals, negative views on the prognosis of those with EDs were expressed by the ASP. Furthermore, confidentiality was found to be a significant barrier to bringing athletes' disclosure of problematic eating or exercise behavior to the fore. The findings of this study add to the limited research exploring attitudes toward EDs in sport and highlights the importance of greater education and openness toward this particular mental health problem. PMID- 26134347 TI - Interplay of Electrostatics and Hydrophobic Effects in the Metamorphic Protein Human Lymphotactin. AB - The human lymphotactin (hLtn) is a protein that features two native states both of which are physiologically relevant: it is a monomer (hLtn10) at 10 degrees C with 200 mM salt and a dimer (hLtn40) at 40 degrees C and without salt. Here we focus on the networks of electrostatic and hydrophobic interactions that display substantial changes upon the conversion from hLtn10 to hLtn40 since they are expected to modulate the relative stability of the two folds. In addition to the Arg 23-Arg 43 interaction discussed in previous work, we find several other like charge pairs that are likely important to the stability of hLtn10. Free energy perturbation calculations are carried out to explicitly evaluate the contribution of the Arg 23-Arg 43 interaction to the hLtn10 stability. hLtn40 features a larger number of salt bridges, and a set of hydrophobic residues undergo major changes in the solvent accessible surface area between hLtn10 and hLtn40, pointing to their importance to the relative stability of the two folds. We also discuss the use of explicit and implicit solvent simulations for characterizing the conformational ensembles under different solution conditions. PMID- 26134348 TI - An Application of Inverse Probability Weighting Estimation of Marginal Structural Models of a Continuous Exposure: Benzodiazepines and Delirium. PMID- 26134349 TI - Dealing with the Serious Underrepresentation of Editors from Low-income Countries. PMID- 26134350 TI - High Birth Prevalence Rates for Congenital Anomalies in South American Regions. PMID- 26134351 TI - Colloid Mobilization in a Fractured Soil during Dry-Wet Cycles: Role of Drying Duration and Flow Path Permeability. AB - In subsurface soils, colloids are mobilized by infiltrating rainwater, but the source of colloids and the process by which colloids are generated between rainfalls are not clear. We examined the effect of drying duration and the spatial variation of soil permeability on the mobilization of in situ colloids in intact soil cores (fractured and heavily weathered saprolite) during dry-wet cycles. Measuring water flux at multiple sampling ports at the core base, we found that water drained through flow paths of different permeability. The duration of antecedent drying cycles affected the amount of mobilized colloids, particularly in high-flux ports that received water from soil regions with a large number of macro- and mesopores. In these ports, the amount of mobilized colloids increased with increased drying duration up to 2.5 days. For drying durations greater than 2.5 days, the amount of mobilized colloids decreased. In contrast, increasing drying duration had a limited effect on colloid mobilization in low-flux ports, which presumably received water from soil regions with fewer macro- and mesopores. On the basis of these results, we attribute this dependence of colloid mobilization upon drying duration to colloid generation from dry pore walls and distribution of colloids in flow paths, which appear to be sensitive to the moisture content of soil after drying and flow path permeability. The results are useful for improving the understanding of colloid mobilization during fluctuating weather conditions. PMID- 26134352 TI - Recent therapeutic approaches for spinal cord injury. AB - A spinal cord injury (SCI) often causes permanent changes in strength and sensation functions below the site of the injury and affects thousands of people each year. Transplantation of stem cells is a promising approach in acute SCI as it may support spinal cord repair. However, in case of chronic SCI greater amounts of nervous tissue have to be regenerated, leaving scaffold transplantation the only feasible option for cellular engraftment and nervous bridging. The aim of regenerative medicine, specifically tissue engineering, is to create a microenvironment that mimics native extracellular matrix (ECM), capable of promoting specific cell-matrix interactions, coaxing cell behavior, and fostering host tissue regeneration. In this regard, nanostructured scaffolds are currently the most promising advanced substrates capable of supporting nervous fiber ingrowth and delivery of neurotrophic drugs. Among them, electrospinning technique and Self-Assembling Peptides (SAPs) have recently attracted lots of attention for their reproducible synthesis and high tailorability. This review highlights clinical trials and recent encouraging strategies for spinal cord repair comprising both cell therapy and nanomedicine. PMID- 26134353 TI - One-strand oligonucleotide probe for fluorescent label-free "turn-on" detection of T4 polynucleotide kinase activity and its inhibition. AB - Thioflavin T (ThT), as one of the most exciting fluorogenic molecules, boasts the "molecular-rotor" ability to induce DNA sequences containing guanine repeats to fold into G-quadruplex structures. It has been demonstrated to sense this change by its remarkable fluorescence enhancement. In this work, taking T4 polynucleotide kinase (PNK) as a model, the ThT/G-quadruplex based platform and lambdaexonuclease (lambdaexo) cleavage reaction were combined to design a label free "turn-on" strategy for fast, simple and accurate detection of T4 PNK activity and its inhibition. In the presence of T4 PNK, the designed thioflavin T based molecular beacon (TMB) DNA probe could be phosphorylated and then digested by the cleavage of lambdaexo, releasing the G-quartets. These then bound to ThT to form ThT/G-quadruplexes with an obvious fluorescence generation, for the "turn on" detection of T4 PNK. In comparison to traditional methods, the proposed TMB probe is convenient, requiring no sophisticated labeling and separation processes and displaying high analytical performance. It exhibits a satisfying detection result for the activity of T4 PNK with a low detection limit of 0.001 U mL(-1). This is not only meaningful for further research on disease-related biochemical processes, but also valuable for molecular-target therapies. PMID- 26134354 TI - Composition-solubility-structure relationships in calcium (alkali) aluminosilicate hydrate (C-(N,K-)A-S-H). AB - The interplay between the solubility, structure and chemical composition of calcium (alkali) aluminosilicate hydrate (C-(N,K-)A-S-H) equilibrated at 50 degrees C is investigated in this paper. The tobermorite-like C-(N,K-)A-S-H products are more crystalline in the presence of alkalis, and generally have larger basal spacings at lower Ca/Si ratios. Both Na and K are incorporated into the interlayer space of the C-(N,K-)A-S-H phases, with more alkali uptake observed at higher alkali and lower Ca content. No relationship between Al and alkali uptake is identified at the Al concentrations investigated (Al/Si <= 0.1). More stable C-(N,K-)A-S-H is formed at higher alkali content, but this factor is only significant in some samples with Ca/Si ratios <=1. Shorter chain lengths are formed at higher alkali and Ca content, and cross-linking between (alumino)silicate chains in the tobermorite-like structure is greatly promoted by increasing alkali and Al concentrations. The calculated solubility products do not depend greatly on the mean chain length in C-(N,K-)A-S-H at a constant Ca/(Al + Si) ratio, or the Al/Si ratio in C-(N,K-)A-S-H. These results are important for understanding the chemical stability of C-(N,K-)A-S-H, which is a key phase formed in the majority of cements and concretes used worldwide. PMID- 26134355 TI - Hydrogen-bonding pincer complexes with two protic N-heterocyclic carbenes from direct metalation of a 1,8-bis(imidazol-1-yl)carbazole by platinum, palladium, and nickel. AB - Pincer protic N-heterocyclic carbene (PNHC) complexes were synthesized by direct metalation, the formation of a metal carbon bond from an unfunctionalized C?H bond in a single synthetic step. Significantly, direct metalation succeeded even for a first-row metal, nickel. The chloride complexes were isolated and then converted to the acetate, triflate, or in the platinum case, a hydride analogue. Crystal structures and (1) H, (13) C, and (15) N NMR data, as well as IR spectra, document the effects of intramolecular hydrogen bonding and the planar but flexible pincer framework. Anti-Markovnikov addition of O?H bonds to alkynes, including catalyzed alkyne hydration, were demonstrated on the Pt triflate analog. PMID- 26134356 TI - A novel mice model of metabolic syndrome: the high-fat-high-fructose diet-fed ICR mice. AB - Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS. PMID- 26134357 TI - Helicobacter sp. MIT 01-6451 infection during fetal and neonatal life in laboratory mice. AB - Helicobacter sp. MIT 01-6451 has been detected in SPF mice kept in Japan. To characterize strain MIT 01-6451, its infection route during fetal and neonatal life and effects on pregnancy were investigated using immunocompetent and immunodeficient mouse strains (BALB/c, C57BL/6, and SCID). MIT 01-6451 was detected in the uterus, vagina, and mammary glands of 50% of infected SCID mice, whereas these tissues were all negative in immunocompetent mice. No fetal infections with MIT 01-6451 were detected at 16-18 days after pregnancy in any mouse strain. In newborn mice, MIT 01-6451 was detected in intestinal tissue of C57BL/6 and SCID mice at 9-11 days after birth, but not in BALB/c mice. The IgA and IgG titers to MIT 01-6451 in sera of C57BL/6 female mice were significantly lower than those of BALB/c mice. Although no significant differences in the number of newborns per litter were observed between MIT 01-6451-infected and MIT 01-6451-free dams, the birth rate was lower in infected SCID mice than in control SCID mice. The present results indicated that MIT 01-6451 infects newborn mice after birth rather than by vertical transmission to the fetus via the placenta and that MIT 01-6451 infection shows opportunistically negative effects on the birth rate. In addition, the maternal immune response may affect infection of newborn mice with MIT 01-6451 through breast milk. PMID- 26134358 TI - Organ failures on admission in patients with Ebola virus disease. PMID- 26134360 TI - End-of-life organ donation: preserving public trust and professional integrity in intensive care medicine. PMID- 26134359 TI - beta-D-Glucan and Candida albicans germ tube antibody in ICU patients with invasive candidiasis. AB - PURPOSE: To assess the performance of (1->3)-beta-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) for the diagnosis of invasive candidiasis (IC) in a prospective cohort of 107 unselected, non-neutropenic ICU patients. METHODS: BDG (cutoff positivity >=80 pg/mL) and CAGTA (cutoff positivity >=1/160) assays were performed twice a week. Confounding factors included amoxicillin clavulanate and piperacillin-tazobactam treatments, recent surgery, Gram-positive bloodstream infection, renal replacement therapy, and enteral nutrition. Patients were classified as neither colonized nor infected (n = 29), Candida spp. colonization (n = 63) (low grade, n = 32; high grade, n = 31), and invasive candidiasis (IC) (n = 15). RESULTS: BDG levels were higher in patients with IC and high-grade colonization than in the remaining groups (p = 0.012), and two consecutive measurements >=80 pg/mL discriminated IC from the remaining groups (sensitivity 80%, specificity 75.7%). For the discrimination between IC and Candida spp. colonization, the AUC for the maximum value of BDG was 0.667 (95% CI 0.544-0.790) and for the maximum value of CAGTA 0.545 (95% CI 0.395-0.694). Significant changes of BDG and CAGTA kinetics in IC patients treated with antifungals were not observed. In patients neither colonized nor infected or with low-grade Candida spp. colonization, none of the confounding factors was associated with a significant increase in BDG positivity. CONCLUSIONS: Two consecutive BDG levels >=80 pg/mL allowed discrimination among IC and high-grade colonization. Systemic antifungal therapy could not be monitored with biomarker kinetics, and BDG levels were not subject to interference by confounding factors in either colonized or infected patients or with low-grade colonization. PMID- 26134361 TI - Associations between family characteristics and parental empowerment in the family, family service situations and the family service system. AB - BACKGROUND: Parental empowerment signifies parents' sense of confidence in managing their children, interacting with services that their children use and improving child care services. High empowerment is associated with parents' resilience to demands and their confidence to make decisions and take actions that positively affect their families. Most families with children access various healthcare and education services. Professionals working in these services are therefore ideally placed to reinforce parental empowerment. However, little is known about the characteristics associated with parental empowerment within a generic sample of parents or in the context of basic child care services. AIM: The aim of this study was to assess how family characteristics are associated with maternal and paternal empowerment in the family, in service situations and in the service system. METHOD: Parental empowerment was measured among 955 parents (mothers = 571; fathers = 384) of children aged 0-9 years using the Generic Family Empowerment Scale. Family characteristics were assessed through questions on children, parents and the life situation. Associations between empowerment and family characteristics were evaluated using one-way analysis of variance and t-test. Parental empowerment was predicted by multiple linear regression analysis. RESULTS: Parents' concerns related to their parenting, such as whether they possessed sufficient skills as a parent or losing their temper with children, as well as experiences of stress in everyday life, were negatively associated with all dimensions of maternal and paternal empowerment. Both determinants were more common and more significant in empowerment than child related problems. CONCLUSION: Promoting parental self-confidence and providing appropriate emotional and concrete support for everyday functioning may reinforce parental empowerment, thereby enhancing families' well-being and coping, as well as improving their access to required services and timely support. Finally, it may facilitate the provision of better services to all families. PMID- 26134362 TI - In situ production of silver nanoparticles on an aldehyde-equipped conjugated porous polymer and subsequent heterogeneous reduction of aromatic nitro groups at room temperature. AB - In a metal-free procedure, chelating thiol groups and an electrophile react to assemble a robust, conjugated porous polymer with pendant aldehyde functionalities. These groups are able to reduce Ag(i) ions to generate, in situ, Ag(0) nanoparticles evenly dispersed in the polymer matrix. The Ag(0)-polymer composite enables selective reduction of aromatic nitro compounds as a heterogeneous catalyst, and can be conveniently recycled multiple times. PMID- 26134363 TI - High frequency of decreased antithrombin level in pregnant women with thrombosis. AB - Venous thromboembolism (VTE) occurs frequently in pregnant women and is a significant cause of maternal death. Hemostatic abnormalities were examined in 18 pregnant women with thrombosis. We studied five families with congenital antithrombin (AT) deficiency, and two families with congenital protein C (PC) deficiency. One woman with PC deficiency showed protein S (PS) Tokushima. The AT activity levels were significantly lower at the onset of thrombosis in the pregnant women than during the stable state. The PS activity and antigen levels were also significantly lower at the onset of thrombosis. In the patients with congenital AT deficiency, AT activity was significantly low in the stable state and decreased further at the onset of thrombosis. Although AT levels were normal before pregnancy, they subsequently decreased and in two cases the patients required the administration of AT after pregnancy. Gene analysis revealed one family with AT Budapest, one family with AT Toyama, and three families with AT Glasgow. Additionally, there were one family with PC Tochigi and one family with combined heterozygous of PC deficiency and PS Tokushima. In conclusion, the deficiency of natural anticoagulants, especially AT, is an important cause of pregnancy-related VTE. PMID- 26134364 TI - Imatinib-induced gastric antral vascular ectasia in three patients with chronic myeloid leukaemia. AB - Imatinib is generally well tolerated, but gastric antral vascular ectasia (GAVE) remains a rare but significant complication of imatinib therapy. Whilst this complication has been described in other disease settings, only one other case of GAVE has been reported in a chronic myeloid leukaemia (CML) patient receiving imatinib. Herein, we present three CML patients with GAVE complicating imatinib therapy. In all cases, GAVE resolved only with cessation of imatinib. This confirms a causal relationship between GAVE and imatinib. GAVE should be considered as a possible cause of anaemia and upper gastrointestinal bleeding in patients receiving imatinib therapy. PMID- 26134365 TI - Serum level of miR-10-5p as a prognostic biomarker for acute myeloid leukemia. AB - MicroRNAs (miRNAs) are a type of small non-coding RNA molecule that play important roles in tumor initiation, chemotherapy response, promotion, and progression by negatively interfering with gene expression. The aim of the present study was to investigate the serum expression status and explore the prognostic significance of miR-10a-5p in acute myeloid leukemia (AML). The serum expression level of miR-10a-5p in de novo AML was significantly higher, compared with that in controls. The area under the receiver operator characteristic (ROC) curve was of 0.831 in the diagnostic value of miR-10a-5p. In the complete remission (CR) group, the serum expression level of miR-10a-5p was similar to that of healthy subjects and demonstrated a significant downtrend when compared to that on the day of diagnosis. Nevertheless, miR-10a-5p expression was found to significantly increase in cases of relapsed AML when compared individually to the CR population. On analysis of the association of miR-10a-5p expression with the clinical characteristics at diagnosis in AML patients, lower CR rates occurred more frequently in the high-expression group. In addition, high miR-10a-5p expression was associated with poorer overall survival (OS). These data suggest that miR-10a-5p may serve as a biomarker useful to improving the management of AML patients. PMID- 26134366 TI - Sensitization of HER2 Positive Breast Cancer Cells to Lapatinib Using Plants Derived Isothiocyanates. AB - Nearly 25% of all breast cancer is characterized by overexpression of HER2 (human epidermal growth factor receptor 2) which leads to overactivation of prosurvival signal transduction pathways, especially through Akt-mTOR-S6K kinases, and results in enhanced proliferation, migration, induction of angiogenesis, and apoptosis inhibition. Anti-HER2 targeted therapies, such as specific monoclonal antibodies or small-molecule tyrosine kinase inhibitors, even in combination, still seem to be insufficient due to incidence of primary or acquired resistance and prevalence of serious side-effects of these drugs. We assumed that combination of compounds that target different levels of the above-mentioned signal transduction pathway might be more effective in eradication of breast cancer cells. In our in vitro research we used a commercially available drug, lapatinib, acting at the level of the receptor in combination with 1 of the plant derived isothiocyanates: sulforaphane, erucin, or sulforaphene, as it has been shown previously that sulforaphane inhibits Akt-mTOR-S6K1 pathway in breast cancer cells. We used 2 HER2 overexpressing breast cancer cell lines, SKBR-3 and BT-474. Combinations of the drug and isothiocyanates considerably decreased their viability. This action was synergistic and was accompanied by a decrease in phosphorylation of HER2, Akt, and S6. Combined treatment induced apoptosis more efficiently than either agent alone; however the most effective was a combination of lapatinib with erucin. These findings might support the optimization of therapy based on lapatinib treatment. PMID- 26134367 TI - Solar Water Splitting Using Semiconductor Photocatalyst Powders. AB - Solar energy conversion is essential to address the gap between energy production and increasing demand. Large scale energy generation from solar energy can only be achieved through equally large scale collection of the solar spectrum. Overall water splitting using heterogeneous photocatalysts with a single semiconductor enables the direct generation of H2 from photoreactors and is one of the most economical technologies for large-scale production of solar fuels. Efficient photocatalyst materials are essential to make this process feasible for future technologies. To achieve efficient photocatalysis for overall water splitting, all of the parameters involved at different time scales should be improved because the overall efficiency is obtained by the multiplication of all these fundamental efficiencies. Accumulation of knowledge ranging from solid-state physics to electrochemistry and a multidisciplinary approach to conduct various measurements are inevitable to be able to understand photocatalysis fully and to improve its efficiency. PMID- 26134368 TI - The fuzzy diagnostic boundaries among left ventricular outflow tract obstruction in hypertensive hypertrophy, hypertrophic cardiomyopathy, and Takotsubo syndrome. PMID- 26134369 TI - MiR-17-5p as circulating biomarkers for the severity of coronary atherosclerosis in coronary artery disease. PMID- 26134370 TI - Multiple and recurrent spontaneous coronary artery dissection: Angiographically visible and invisible dissections in the same patient. PMID- 26134371 TI - Matrix metalloproteinases and their tissue inhibitor after reperfused ST elevation myocardial infarction treated with doxycycline. Insights from the TIPTOP trial. AB - BACKGROUND: The TIPTOP (Early Short-term Doxycycline Therapy In Patients with Acute Myocardial Infarction and Left Ventricular Dysfunction to Prevent The Ominous Progression to Adverse Remodelling) trial demonstrated that a timely, short-term therapy with doxycycline is able to reduce LV dilation, and both infarct size and severity in patients treated with primary percutaneous intervention (pPCI) for a first ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. In this secondary, pre-defined analysis of the TIPTOP trial we evaluated the relationship between doxycycline and plasma levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). METHODS: In 106 of the 110 (96%) patients enrolled in the TIPTOP trial, plasma MMPs and TIMPs were measured at baseline, and at post-STEMI days 1, 7, 30 and 180. To evaluate the remodeling process, 2D-Echo studies were performed at baseline and at 6months. A (99m)Tc-SPECT was performed to evaluate the 6-month infarct size and severity. RESULTS: Doxycycline therapy was independently related to higher plasma TIMP-2 levels at day 7 (p<0.05). Plasma TIMP-2 levels above the median value at day 7 were correlated with the 6-month smaller infarct size (3% [0%-16%] vs. 12% [0%-30%], p=0.002) and severity (0.55 [0.44-0.64] vs. 0.45 [0.29-0.60], p=0.002), and LV dilation (-1ml/m(2) [from -7ml/m(2) to 9ml/m(2)] vs. 3ml/m(2) [from -2ml/m(2) to 19ml/m(2)], p=0.04), compared to their counterpart. CONCLUSIONS: In this clinical setting, doxycycline therapy results in higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6month infarct size and severity as well as LV dilation. PMID- 26134372 TI - Effect of personalized external aortic root support on aortic root motion and distension in Marfan syndrome patients. AB - OBJECTIVE: Personalized external aortic root support (PEARS) is a novel surgical approach with the aim of stabilizing the aortic root size and decreasing risk of dissection in Marfan syndrome patients. A bespoke polymer mesh tailored to each patient's individual aorta shape is produced by modeling and then surgically implanted. The aim of this study is to assess the mechanical effects of PEARS on the aortic root systolic downward motion (an important determinant of aortic wall stress), aortic root distension and on the left ventricle (LV). METHODS/RESULTS: A cohort of 27 Marfan patients had a prophylactic PEARS surgery between 2004 and 2012 with 24 having preoperative and follow-up cardiovascular magnetic resonance imaging studies. Systolic downward aortic root motion, aortic root distension, LV volumes/mass and mitral annular systolic excursion before the operation and in the latest follow-up were measured randomly and blinded. After a median follow-up of 50.5 (IQR 25.5-72) months following implantation of PEARS, systolic downward motion of aortic root was significantly decreased (12.6+/-3.6mm pre-operation vs 7.9+/-2.9mm latest follow-up, p<0.00001). There was a tendency for a decrease in systolic aortic root distension but this was not significant (median 4.5% vs 2%, p=0.35). There was no significant change in LV volumes, ejection fraction, mass and mitral annular systolic excursion in follow-up. CONCLUSIONS: PEARS surgery decreases systolic downward aortic root motion which is an important determinant of longitudinal aortic wall stress. Aortic wall distension and Windkessel function are not significantly impaired in the follow-up after implantation of the mesh which is also supported by the lack of deterioration of LV volumes or mass. PMID- 26134373 TI - Identifying and Eliminating Emissive Sub-bandgap States in Thin Films of PbS Nanocrystals. AB - Chemical oxidation of under-charged Pb atoms reduces the density of trap states by a factor of 40 in films of colloidal PbS quantum dots for devices. These emissive sub-bandgap states are a byproduct of several standard ligand-exchange procedures. X-ray photoelectron spectro-scopy measurements and density function theory simulations demonstrate that they are associated with under-charged Pb. PMID- 26134374 TI - A Meta-Analysis of Mesenchymal Stem Cells in Animal Models of Parkinson's Disease. AB - Multiple studies have been performed to evaluate the effects of mesenchymal stem cells (MSCs) in animal models of Parkinson's disease (PD). We performed a meta analysis to estimate the treatment effect of unmodified MSCs on behavioral outcomes in preclinical studies of PD. We performed a systematic literature search to identify studies that used behavioral testing to evaluate the treatment effect of unmodified MSCs in PD models. Meta-analysis was used to determine pooled effect size for rotational behavior and limb function, and meta-regression was performed to explore sources of heterogeneity. Twenty-five studies, including three delivery routes, a wide range of doses, and multiple PD models, were examined. Significant improvement was seen in the pooled standardized mean difference (SMD) for both rotational behavior [SMD: 1.24, 95% confidence interval (95% CI): 0.84, 1.64] and limb function (SMD: 0.84, 95% CI: 0.01, 1.66). Using meta-regression, intravenous administration and higher dose had a larger effect on limb function. Treatment with MSCs improves behavioral outcomes in PD models. Our analyses suggest that MSCs could be considered for early-stage clinical trials in the treatment of PD. PMID- 26134375 TI - Involvement of doublesex and mab-3-related transcription factors in human female germ cell development demonstrated by xenograft and interference RNA strategies. PMID- 26134379 TI - High-Q/V Monolithic Diamond Microdisks Fabricated with Quasi-isotropic Etching. AB - Optical microcavities enhance light-matter interactions and are essential for many experiments in solid state quantum optics, optomechanics, and nonlinear optics. Single crystal diamond microcavities are particularly sought after for applications involving diamond quantum emitters, such as nitrogen vacancy centers, and for experiments that benefit from diamond's excellent optical and mechanical properties. Light-matter coupling rates in experiments involving microcavities typically scale with Q/V, where Q and V are the microcavity quality factor and mode-volume, respectively. Here we demonstrate that microdisk whispering gallery mode cavities with high Q/V can be fabricated directly from bulk single crystal diamond. By using a quasi-isotropic oxygen plasma to etch along diamond crystal planes and undercut passivated diamond structures, we create monolithic diamond microdisks. Fiber taper based measurements show that these devices support TE- and TM-like optical modes with Q > 1.1 * 10(5) and V < 11(lambda/n) (3) at a wavelength of 1.5 MUm. PMID- 26134380 TI - Recurrent human papillomavirus-related airway squamous cell carcinomas. PMID- 26134381 TI - Cinnamomum cassia: an implication of serotonin reuptake inhibition in animal models of depression. AB - The aim of the study was to explore the traditional use of Cinnamomum cassia against depression. The standardised methanolic extract of the bark of C. cassia was evaluated for antidepressant activity using various behavioural tests, i.e. tail suspension test (TST), forced swim test (FST) and locomotor activity test. The serotonergic and noradrenergic modulation was assessed using 5 hydroxytryptophan (5-HTP)-induced head twitches and yohimbine potentiation tests, respectively. The fluoxetine and phenelzine were used as positive controls in the study. The C. cassia extract significantly decreased the immobility time in TST (maximum effective dose tested was 50 mg/kg) while no effect was observed in FST and locomotor activity test. The extract significantly increased the 5-HTP induced head twitches while yohimbine-induced lethality remained unaltered. The aforementioned results are similar to that caused by fluoxetine. The standardised methanolic extract of C. cassia demonstrated antidepressant activity that can be attributed to rise in serotonin levels. PMID- 26134382 TI - Polysaccharide Modification through Green Technology: Role of Endodextranase in Improving the Physicochemical Properties of (1->3)(1->6)-alpha-D-Glucan. AB - The structure and properties of bioengineered (1->3)(1->6)-alpha-D-glucan subjected to endodextranase treatment were investigated. Upon enzyme treatment, OD220 and Mw decreased substantially during the first 60 min and thereafter slowed as the modification progressed. Compared to the native glucan, the modified sample solution had a lighter opalescent, bluish-white color. The morphological analysis revealed that bioengineered glucan produced quite a few small particles after hydrolysis. The molecular weight distribution curve gradually shifted to the low Mw region with a significant broadening distribution, and the chain hydrolysis reaction followed a combination of zeroth- and first-order processes. The NMR results showed some specific alpha-1,6 linkages of glucan chains were cleaved with enzyme treatment. The viscosity of modified glucan solution was markedly reduced, and the Newtonian plateaus were also observed at high shear rates (10-100 1/s). The above results suggested that the modified (1->3)(1->6)-alpha-D-glucan showed a tailor-made solution character similar to that of arabic gum and would be used as a novel food gum substitute in the design of artificial carbohydrate-based foods. PMID- 26134383 TI - Latest advances in molecular topology applications for drug discovery. AB - INTRODUCTION: Molecular topology (MT) has emerged in recent years as a powerful approach for the in silico generation of new drugs. In the last decade, its application has become more and more popular among the leading research groups in the field of quantitative structure-activity relationships (QSAR) and drug design. This has, in turn, contributed to the rapid development of new techniques and applications of MT in QSAR studies, as well as the introduction of new topological indices. AREAS COVERED: This review collates the main innovative techniques in the field of MT and provides a description of the novel topological indices recently introduced, through an exhaustive recompilation of the most significant works carried out by the leading research groups in the field of drug design and discovery. The objective is to show the importance of MT methods combined with the effectiveness of the descriptors. EXPERT OPINION: Recent years have witnessed a remarkable rise in QSAR methods based on MT and its application to drug design. New methodologies have been introduced in the area such as QSAR multi-target, Markov networks or perturbation methods. Moreover, novel topological indices, such as Bourgas' descriptors and other new concepts as the derivative of a graph or cliques capable to distinguish between conformers, have also been introduced. New drugs have also been discovered, including anticonvulsants, anineoplastics, antimalarials or antiallergics, just to name a few. In the authors' opinion, MT and QSAR have moved from an attractive possibility to representing a foundation stone in the process of drug discovery. PMID- 26134384 TI - Hyporeactivity of Alveolar Macrophages and Higher Respiratory Cell Permissivity Characterize DBA/2J Mice Infected by Influenza A Virus. AB - Influenza A virus remains a major public health problem. Mouse models have been widely used to study influenza infection in mammals. DBA/2J and C57BL/6J represent extremes in terms of susceptibility to influenza A infection among inbred laboratory mouse strains. Several studies focused specifically on the factors responsible for the susceptibility of DBA/2J or the resistance of C57BL/6J and resulted in impressive lists of candidate genes or factors over- or underexpressed in one of the strains. We adopted a different phenotypical approach to identify the critical steps of the infection process accounting for the differences between DBA/2J and C57BL/6J strains. We concluded that both a dysfunction of alveolar macrophages and an increased permissivity of respiratory cells rendered DBA/2J more susceptible to influenza infection. PMID- 26134385 TI - Predictive and prognostic cancer biomarkers revisited. AB - While both prognostic and predictive cancer biomarkers predict clinical outcome, the term 'predictive biomarker' is reserved for the association of a specific therapy with a specific clinical outcome. The advent of genomic signatures and next generation sequencing as candidate predictive biomarkers has led to lengthy and expensive processes for biomarker qualification. The urgency to bring novel predictive cancer biomarkers to practice faster and cheaper requires strategies to lower the bar to biomarker implementation. Three strategies are suggested: identify biomarkers closely coupled to biologic mechanism associated with the clinical endpoint and scalable from cells to humans; identify biomarkers that can be reliably detected and quantified; and assess biomarkers by capacity to reduce toxicity as well as to increase therapy efficacy. Biomarker selection directly and closely related to production of end points by biologic mechanism demonstrated by a ladder of evidence should require less burden of proof clinically than biomarkers that are merely associative. PMID- 26134386 TI - Lower periprosthetic bone loss and good fixation of an ultra-short stem compared to a conventional stem in uncemented total hip arthroplasty. AB - BACKGROUND AND PURPOSE: We hypothesized that an ultra-short stem would load the proximal femur in a more physiological way and could therefore reduce the adaptive periprosthetic bone loss known as stress shielding. PATIENTS AND METHODS: 51 patients with primary hip osteoarthritis were randomized to total hip arthroplasty (THA) with either an ultra-short stem or a conventional tapered stem. The primary endpoint was change in periprosthetic bone mineral density (BMD), measured with dual-energy x-ray absorptiometry (DXA), in Gruen zones 1 and 7, two years after surgery. Secondary endpoints were change in periprosthetic BMD in the entire periprosthetic region, i.e. Gruen zones 1 through 7, stem migration measured with radiostereometric analysis (RSA), and function measured with self administered functional scores. RESULTS: The periprosthetic decrease in BMD was statistically significantly lower with the ultra-short stem. In Gruen zone 1, the mean difference was 18% (95% CI: -27% to -10%). In zone 7, the difference was 5% (CI: -12% to -3%) and for Gruen zones 1-7 the difference was also 5% (CI: -9% to 2%). During the first 6 weeks postoperatively, the ultra-short stems migrated 0.77 mm more on average than the conventional stems. 3 months after surgery, no further migration was seen. The functional scores improved during the study and were similar in the 2 groups. INTERPRETATION: Up to 2 years after total hip arthroplasty, compared to the conventional tapered stem the ultra-short uncemented anatomical stem induced lower periprosthetic bone loss and had equally excellent stem fixation and clinical outcome. PMID- 26134387 TI - Reducing Concurrent Sexual Partnerships Among Blacks in the Rural Southeastern United States: Development of Narrative Messages for a Radio Campaign. AB - In the United States, heterosexual transmission of HIV infection is dramatically higher among Blacks than among Whites. Overlapping (concurrent) sexual partnerships promote HIV transmission. The authors describe their process for developing a radio campaign (Escape the Web) to raise awareness among 18-34-year old Black adults of the effect of concurrency on HIV transmission in the rural South. Radio is a powerful channel for the delivery of narrative-style health messages. Through six focus groups (n = 51) and 42 intercept interviews, the authors explored attitudes toward concurrency and solicited feedback on sample messages. Men were advised to (a) end concurrent partnerships and not to begin new ones; (b) use condoms consistently with all partners; and (c) tell others about the risks of concurrency and benefits of ending concurrent partnerships. The narrative portrayed risky behaviors that trigger initiation of casual partnerships. Women were advised to (a) end partnerships in which they are not their partner's only partner; (b) use condoms consistently with all partners; and (c) tell others about the risks of concurrency and benefits of ending concurrent partnerships. Messages for all advised better modeling for children. PMID- 26134388 TI - Dietary modulation of the gut microbiota--a randomised controlled trial in obese postmenopausal women. AB - The gut microbiota has been implicated in obesity and its progression towards metabolic disease. Dietary interventions that target the gut microbiota have been suggested to improve metabolic health. The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity. A total of fifty-eight obese postmenopausal women were randomised to a single blinded, parallel-group intervention of 6-week duration, with a daily intake of either L. paracasei F19 (9.4 * 1010 colony-forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models. The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test (P< 0.05) and improved insulin sensitivity measured by Matsuda index (P< 0.05). Comparison of gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage showed alterations in abundance of thirty-three metagenomic species (P< 0.01), including decreased relative abundance of eight Faecalibacterium species. These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity. The intake of L. paracasei F19 did not modulate metabolic markers compared with placebo. In conclusion, flaxseed mucilage improves insulin sensitivity and alters the gut microbiota; however, the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species. PMID- 26134390 TI - Doctor Janusz M. Szajewski, MD (1924-2015). PMID- 26134389 TI - Nanotechnology applications in hematological malignancies (Review). AB - A major limitation to current cancer therapies is the development of therapy related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up. PMID- 26134391 TI - Biomarkers in heart failure: ready for use? PMID- 26134392 TI - Biomarkers for prognosis in atrial fibrillation: unfulfilled hopes. PMID- 26134393 TI - Manual aspiration thrombectomy complemented with local thrombolysis for acute renal artery embolism. PMID- 26134394 TI - Correction for Wexler et al., Default perception of high-speed motion. PMID- 26134395 TI - Correction for Wang et al., Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway. PMID- 26134397 TI - Corrections for Elmendorf et al., Experiment, monitoring, and gradient methods used to infer climate change effects on plant communities yield consistent patterns. PMID- 26134398 TI - Pre-T-cell receptor binds MHC: Implications for thymocyte signaling and selection. PMID- 26134396 TI - A lipid switch unlocks Parkinson's disease-associated ATP13A2. AB - ATP13A2 is a lysosomal P-type transport ATPase that has been implicated in Kufor Rakeb syndrome and Parkinson's disease (PD), providing protection against alpha synuclein, Mn(2+), and Zn(2+) toxicity in various model systems. So far, the molecular function and regulation of ATP13A2 remains undetermined. Here, we demonstrate that ATP13A2 contains a unique N-terminal hydrophobic extension that lies on the cytosolic membrane surface of the lysosome, where it interacts with the lysosomal signaling lipids phosphatidic acid (PA) and phosphatidylinositol(3,5)bisphosphate [PI(3,5)P2]. We further demonstrate that ATP13A2 accumulates in an inactive autophosphorylated state and that PA and PI(3,5)P2 stimulate the autophosphorylation of ATP13A2. In a cellular model of PD, only catalytically active ATP13A2 offers cellular protection against rotenone induced mitochondrial stress, which relies on the availability of PA and PI(3,5)P2. Thus, the N-terminal binding of PA and PI(3,5)P2 emerges as a key to unlock the activity of ATP13A2, which may offer a therapeutic strategy to activate ATP13A2 and thereby reduce alpha-synuclein toxicity or mitochondrial stress in PD or related disorders. PMID- 26134401 TI - Reduced proliferation in breast cancer cells contacting the neighboring adipocytes in human breast cancer tissues. PMID- 26134399 TI - Effect of platelet-rich plasma on the healing of cutaneous defects exposed to acute to chronic wounds: a clinico-histopathologic study in rabbits. AB - BACKGROUND: Platelet-rich plasma (PRP) contains numerous growth factors to promote wound healing and angiogenesis. The aim of this study was to gain further information about the benefits of platelet-rich-plasma for healing cutaneous acute to chronic wounds. METHODS: A total of 30 New Zealand albino rabbits (n = 15/group) were randomly assigned to two experimental groups: control group, and PRP group. Bilateral resection defects measuring 3 cm were surgically created on the dorsolateral of the cutaneous in animals and the defects were randomly divided into two mentioned groups. Wound area, neovascularization, size and epithelialization were compared on days 7, 14 and 21 post-wounding. Histopathological analyses were conducted on 15 specimens from each group after sacrifice by the cellular aspects of the regeneration of the tissue. RESULTS: Our results were indicated that the wound area of PRP was smaller than that in the non-treated group on days 7, 14 and 21. Furthermore, a significant decrease of the wound size was observed in PRP groups that were significantly greater than that in the control group. A significant increase of the mean vascular density was noted in the PRP treated groups compared to the control groups at day 14 and especially day 21. This results indicated that PRP treated group' enhanced angiogenesis at the wound beds as compared to no treatment group. CONCLUSION: These results could be useful for researchers in the growing fields of tissue repair and experimental wound healing. Further studies will be essential to determine the role of PRP in clinical practice. PMID- 26134400 TI - Preoperative serum 8-hydroxydeoxyguanosine is associated with chemoresistance and is a powerful prognostic factor in endometrioid-type epithelial ovarian cancer. AB - BACKGROUND: Oxidative stress is a widely seen phenomenon in several carcinomas. Increasing evidence also suggests that it has a significant role in the development of epithelial ovarian carcinoma (EOC). 8-Hydroxydeoxyguanosine (8 OHdG) is one of the main indicators of oxidative stress and increased expression of 8-OHdG has previously been seen in EOC. DJ-1 is an oncoprotein connected to oxidative stress regulation, but its role in ovarian cancer is not well known. We investigated redox status in different histotypes of EOC by measuring serum 8 OHdG and DJ-1 concentrations and their associations with known prognostic factors. METHODS: Serum samples from newly diagnosed EOC patients were collected in 1996-2009 and stored at the Department of Obstetrics and Gynecology, Oulu University Hospital. Serum 8-OHdG and DJ-1 levels were measured by using commercially available ELISA kits. Clinical data was gathered retrospectively from the patients' files. Results were analyzed by using SPSS software. RESULTS: In total, 112 patient samples were analyzed (38 serous, 20 mucinous, 34 endometrioid and 20 clear-cell). High serum 8-OHdG levels were associated with poor overall survival (OS) (p = 0.019), poor disease-free survival (DFS) (p = 0.020), platinum resistance (p = 0.002), serous histology versus other (p = 0.033), stage III-IV versus I-II (p = 0.009) and suboptimal surgical outcome (p = 0.012). Regarding histotypes, in the endometrioid EOC group in particular, serum 8-OHdG levels were significantly associated with poor DFS (p = 0.005), suboptimal surgical outcome (p = 0.025), and platinum resistance (p = 0.007). The prognostic significance of 8-OHdG in patients with endometrioid cancer in terms of DFS was confirmed in Cox regression analysis. High DJ-1 levels were associated with high histological grade (p = 0.029) and nonsignificantly associated with serous histology vs. other histology (p = 0.089). CONCLUSIONS: An elevated serum 8-OHdG level is a significant predictor of poor prognosis, especially in cases of the endometrioid subtype of ovarian carcinoma. High 8-OHdG levels are associated with all traditional factors of poor prognosis in ovarian cancer and they also predict earlier development of platinum resistance. These results could be valuable when deciding the primary treatment mode for EOC patients. PMID- 26134402 TI - Identification of key amino acids responsible for the distinct aggregation properties of microtubule-associated protein 2 and tau. AB - The carboxyl-terminal sequence of tau composes the framework for its intracellular inclusions that appear in diverse neurodegenerative disorders known as tauopathies. However, microtubule-associated protein 2 (MAP2), which contains a homologous carboxyl-terminal sequence of tau, is undetectable in the mature tau inclusions. The mechanisms underlying this phenomenon have remained largely unknown. Here, we show that tau and MAP2 have different aggregation properties: tau aggregates to form filaments but MAP2 remains to be granules. Exchanging (221) YKPV(224) of tau (0N3R) near the PHF6 motif for (340) TKKI(343) of MAP2c profoundly changed aggregation properties, suggesting that the YKPV motif is important for filament formation, whereas the TKKI motif is for granule formation. Thus, these minimal sequences may determine the different fates of tau and MAP2 in the formation of inclusions in tauopathies. Tau and microtubule associated protein 2 (MAP2) are homologous microtubule-associated proteins in neurons. So far, it is largely unknown why tau but not MAP2 is selectively involved in the filamentous inclusions (neurofibrillary tangles, NFT) formation in tauopathies, including Alzheimer's disease. In this study, we found that the difference of only two amino acids in tau and MAP2 sequences may determine their different fates in tauopathies. These results may lead to the elucidation of tau deregulation in pathological conditions. PMID- 26134403 TI - Case management in primary palliative care is associated more strongly with organisational than with patient characteristics: results from a cross-sectional prospective study. AB - BACKGROUND: Case managers have been introduced in Dutch primary palliative care; these are nurses with expertise in palliative care who offer support to patients and informal carers in addition to the care provided by the general practitioner and home care nurses. This study aims to describe support and investigate what characteristics of patients and the organizational setting are related to the number of contacts and to the number of times topics are discussed between the case manager and patients and/or informal carers. METHODS: Prospective study following cancer patients (n = 662) receiving support from a palliative care case manager in Dutch primary care, using registration forms filled out by the case manager after contact with the patient and/or informal carer. In backward linear regression, the association was studied between patient or organizational characteristics and the number of contacts and the number of times conversation topics were discussed. RESULTS: Organizational characteristics add more to explained variability in data than patient characteristics. Case managers provide support in a flexible manner with regard to the number, mode, persons present, and duration of contacts. Support covered all domains of palliative care, with most attention given to physical complaints, life expectancy and psychological aspects. CONCLUSIONS: Support offered by the case managers is prompted by characteristics of the organization for which they work. This is contradictory to the idea of patient centered care highly valued in palliative care. PMID- 26134404 TI - Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events. AB - BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention. PMID- 26134405 TI - alpha2-Macroglobulin Can Crosslink Multiple Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) Molecules and May Facilitate Adhesion of Parasitized Erythrocytes. AB - Rosetting, the adhesion of Plasmodium falciparum-infected erythrocytes to uninfected erythrocytes, involves clonal variants of the parasite protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) and soluble serum factors. While rosetting is a well-known phenotypic marker of parasites associated with severe malaria, the reason for this association remains unclear, as do the molecular details of the interaction between the infected erythrocyte (IE) and the adhering erythrocytes. Here, we identify for the first time a single serum factor, the abundant serum protease inhibitor alpha2-macroglobulin (alpha2M), which is both required and sufficient for rosetting mediated by the PfEMP1 protein HB3VAR06 and some other rosette-mediating PfEMP1 proteins. We map the alpha2M binding site to the C terminal end of HB3VAR06, and demonstrate that alpha2M can bind at least four HB3VAR06 proteins, plausibly augmenting their combined avidity for host receptors. IgM has previously been identified as a rosette-facilitating soluble factor that acts in a similar way, but it cannot induce rosetting on its own. This is in contrast to alpha2M and probably due to the more limited cross-linking potential of IgM. Nevertheless, we show that IgM works synergistically with alpha2M and markedly lowers the concentration of alpha2M required for rosetting. Finally, HB3VAR06+ IEs share the capacity to bind alpha2M with subsets of genotypically distinct P. falciparum isolates forming rosettes in vitro and of patient parasite isolates ex vivo. Together, our results are evidence that P. falciparum parasites exploit alpha2M (and IgM) to expand the repertoire of host receptors available for PfEMP1-mediated IE adhesion, such as the erythrocyte carbohydrate moieties that lead to formation of rosettes. It is likely that this mechanism also affects IE adhesion to receptors on vascular endothelium. The study opens opportunities for broad-ranging immunological interventions targeting the alpha2M--(and IgM-) binding domains of PfEMP1, which would be independent of the host receptor specificity of clinically important PfEMP1 antigens. PMID- 26134407 TI - Gonad establishment during asexual reproduction in the annelid Pristina leidyi. AB - Animals that can reproduce by both asexual agametic reproduction and sexual reproduction must transmit or re-establish their germ line post-embryonically. Although such a dual reproductive mode has evolved repeatedly among animals, how asexually produced individuals establish their germ line remains poorly understood in most groups. We investigated germ line development in the annelid Pristina leidyi, a species that typically reproduces asexually by paratomic fission, intercalating a new tail and head in the middle of the body followed by splitting. We found that in fissioning individuals, gonads occur in anterior segments in the anterior-most individual as well as in new heads forming within fission zones. Homologs of the germ line/multipotency genes piwi, vasa, and nanos are expressed in the gonads, as well as in proliferative tissues including the posterior growth zone, fission zone, and regeneration blastema. In fissioning animals, certain cells on the ventral nerve cord express a homolog of piwi, are abundant near fission zones, and sometimes make contact with gonads. Such cells are typically undetectable near the blastema and posterior growth zone. Time lapse imaging provides direct evidence that cells on the ventral nerve cord migrate preferentially towards fission zones. Our findings indicate that gonads form routinely in fissioning individuals, that a population of piwi-positive cells on the ventral nerve cord is associated with fission and gonads, and that cells resembling these piwi-positive cells migrate along the ventral nerve cord. We suggest that the piwi-positive ventral cells are germ cells that transmit the germ line across asexually produced individuals via migration along the ventral nerve cord. PMID- 26134406 TI - Dissecting the Mechanisms of Doxorubicin and Oxidative Stress-Induced Cytotoxicity: The Involvement of Actin Cytoskeleton and ROCK1. AB - We have recently reported that ROCK1 deficiency in mouse embryonic fibroblasts (MEF) has superior anti-apoptotic and pro-survival effects than antioxidants against doxorubicin, a chemotherapeutic drug. Although oxidative stress is the most widely accepted mechanism, our studies suggest that ROCK1-dependent actin cytoskeleton remodeling plays a more important role in mediating doxorubicin cytotoxicity on MEFs. To further explore the contributions of ROCK1-dependent actin cytoskeleton remodeling in response to stress, this study investigates the mechanistic differences between the cytotoxic effects of doxorubicin versus hydrogen peroxide (H2O2), with a focus on cytoskeleton alterations, apoptosis and necrosis induction. We found that both types of stress induce caspase activation but with different temporal patterns and magnitudes in MEFs: H2O2 induces the maximal levels (2 to 4-fold) of activation of caspases 3, 8, and 9 within 4 h, while doxorubicin induces much higher maximal levels (15 to 25-fold) of caspases activation at later time points (16-24 h). In addition, necrosis induced by H2O2 reaches maximal levels within 4 h while doxorubicin-induced necrosis largely occurs at 16-24 h secondary to apoptosis. Moreover, both types of stress induce actin cytoskeleton remodeling but with different characteristics: H2O2 induces disruption of stress fibers associated with cytosolic translocation of phosphorylated myosin light chain (p-MLC) from stress fibers, while doxorubicin induces cortical F-actin formation associated with cortical translocation of p MLC from central stress fibers. Furthermore, N-acetylcysteine (an antioxidant) is a potent suppressor for H2O2-induced cytotoxic effects including caspase activation, necrosis, and cell detachment, but shows a much reduced inhibition on doxorubicin-induced changes. On the other hand, ROCK1 deficiency is a more potent suppressor for the cytotoxic effects induced by doxorubicin than by H2O2. These results support the notion that doxorubicin induces caspase activation, necrosis, and actin cytoskeleton alterations largely through ROCK1-dependent and oxidative stress-independent pathways. PMID- 26134408 TI - Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line. AB - Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 degrees C. The 3 (4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer. PMID- 26134410 TI - Photoluminescence from low thermal budget silicon nano-crystals in silica. AB - We have developed a novel method to fabricate Si nanocrystals in a silica matrix with a considerably reduced thermal budget using pulsed laser deposition. Normally, Si nanocrystals are formed through phase separation by annealing a Si rich SiO2 film at 1100 degrees C; we show Si nanocrystal formation in as deposited films at 550 degrees C. We suggest the mechanism for this is through surface diffusion during deposition. We also show the ability to vary the size of these nanocrystals by adjusting the deposition conditions and can increase their size through annealing. If the nanocrystals are small they have excellent photoluminescence properties however larger nanocrystals have poor luminescence. PMID- 26134409 TI - Treatment of Prion Disease with Heterologous Prion Proteins. AB - Prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep are fatal neurodegenerative diseases for which there is no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPsc or PrPres). Both in vitro (cell culture and cell free conversion assays) and in vivo (animal) studies have demonstrated the strong dependence of this conversion process on protein sequence homology between the initial prion inoculum and the host's own cellular prion protein. The presence of non-homologous (heterologous) proteins is often inhibitory to this conversion process. We hypothesize that the presence of heterologous prion proteins from one species might therefore constitute an effective treatment for prion disease in another species. To test this hypothesis, we infected mice intracerebrally with murine adapted RML-Chandler scrapie and treated them with heterologous prion protein (purified bacterially expressed recombinant hamster prion protein) or vehicle alone. Treated animals demonstrated reduced disease associated pathology, decreased accumulation of protease-resistant disease-associated prion protein, with delayed onset of clinical symptoms and motor deficits. This was concomitant with significantly increased survival times relative to mock-treated animals. These results provide proof of principle that recombinant hamster prion proteins can effectively and safely inhibit prion disease in mice, and suggest that hamster or other non-human prion proteins may be a viable treatment for prion diseases in humans. PMID- 26134411 TI - Comparison of the Oral Microbiomes of Canines and Their Owners Using Next Generation Sequencing. AB - The oral microbiome, which is closely associated with many diseases, and the resident pathogenic oral bacteria, which can be transferred by close physical contact, are important public health considerations. Although the dog is the most common companion animal, the composition of the canine oral microbiome, which may include human pathogenic bacteria, and its relationship with that of their owners are unclear. In this study, 16S rDNA pyrosequencing was used to compare the oral microbiomes of 10 dogs and their owners and to identify zoonotic pathogens. Pyrosequencing revealed 246 operational taxonomic units in the 10 samples, representing 57 genera from eight bacterial phyla. Firmicutes (57.6%), Proteobacteria (21.6%), Bacteroidetes (9.8%), Actinobacteria (7.1%), and Fusobacteria (3.9%) were the predominant phyla in the human oral samples, whereas Proteobacteria (25.7%), Actinobacteria (21%), Bacteroidetes (19.7%), Firmicutes (19.3%), and Fusobacteria (12.3%) were predominant in the canine oral samples. The predominant genera in the human samples were Streptococcus (43.9%), Neisseria (10.3%), Haemophilus (9.6%), Prevotella (8.4%), and Veillonella (8.1%), whereas the predominant genera in the canine samples were Actinomyces (17.2%), Unknown (16.8), Porphyromonas (14.8), Fusobacterium (11.8), and Neisseria (7.2%). The oral microbiomes of dogs and their owners were appreciably different, and similarity in the microbiomes of canines and their owners was not correlated with residing in the same household. Oral-to-oral transfer of Neisseria shayeganii, Porphyromonas canigingivalis, Tannerella forsythia, and Streptococcus minor from dogs to humans was suspected. The finding of potentially zoonotic and periodontopathic bacteria in the canine oral microbiome may be a public health concern. PMID- 26134412 TI - A Collision Risk Model to Predict Avian Fatalities at Wind Facilities: An Example Using Golden Eagles, Aquila chrysaetos. AB - Wind power is a major candidate in the search for clean, renewable energy. Beyond the technical and economic challenges of wind energy development are environmental issues that may restrict its growth. Avian fatalities due to collisions with rotating turbine blades are a leading concern and there is considerable uncertainty surrounding avian collision risk at wind facilities. This uncertainty is not reflected in many models currently used to predict the avian fatalities that would result from proposed wind developments. We introduce a method to predict fatalities at wind facilities, based on pre-construction monitoring. Our method can directly incorporate uncertainty into the estimates of avian fatalities and can be updated if information on the true number of fatalities becomes available from post-construction carcass monitoring. Our model considers only three parameters: hazardous footprint, bird exposure to turbines and collision probability. By using a Bayesian analytical framework we account for uncertainties in these values, which are then reflected in our predictions and can be reduced through subsequent data collection. The simplicity of our approach makes it accessible to ecologists concerned with the impact of wind development, as well as to managers, policy makers and industry interested in its implementation in real-world decision contexts. We demonstrate the utility of our method by predicting golden eagle (Aquila chrysaetos) fatalities at a wind installation in the United States. Using pre-construction data, we predicted 7.48 eagle fatalities year-1 (95% CI: (1.1, 19.81)). The U.S. Fish and Wildlife Service uses the 80th quantile (11.0 eagle fatalities year-1) in their permitting process to ensure there is only a 20% chance a wind facility exceeds the authorized fatalities. Once data were available from two-years of post construction monitoring, we updated the fatality estimate to 4.8 eagle fatalities year-1 (95% CI: (1.76, 9.4); 80th quantile, 6.3). In this case, the increased precision in the fatality prediction lowered the level of authorized take, and thus lowered the required amount of compensatory mitigation. PMID- 26134414 TI - Manual preferences for visually- and haptically-guided grasping. AB - Studies have shown that individuals exhibit a right-hand preference for grasping during visually-guided tasks. Recently, we have found that when vision is occluded right-hand preference decreases dramatically. It remains unknown however, if this decrease is a result of visual occlusion or the effects of relying only on haptic feedback. Therefore, in the present study, we sought to explore the contributions of vision and haptics (separately and in conjunction) to hand preference for grasping. Right- and left-handed individuals were tested on a block building task under four different visual and haptic conditions: 1) vision/normal haptic feedback (V/H), 2) no vision/normal haptic feedback (NV/H), 3) vision/constrained haptic feedback (V/Constrained-H), and 4) no vision/constrained haptic feedback (NV/Constrained-H). Vision was occluded using a blindfold and haptic feedback was constrained by asking participants to wear textured gloves. Right-handed individuals displayed a right-hand preference when vision was available (V/H and V/Constrained-H groups), but this preference was much greater when haptic feedback was constrained (V/Constrained-H group). When vision was occluded and haptic feedback was used to complete the task (NV/H) no hand preference was found. Finally hand preference was similar between the V/H and the NV/Constrained-H groups. For left-handed individuals, no differences in hand use were found between the different sensory groups, but the NV/H group showed a clear left-hand preference for haptically-guided grasping. The results suggest that haptics plays an important role in hand preference for grasping. Furthermore, they support a left-hand/right-hemisphere specialization for haptically-guided grasping (regardless of handedness) and a right-hand/left hemisphere specialization for visually-guided grasping (at least in right-handed individuals). PMID- 26134413 TI - FOXL2 modulates cartilage, skeletal development and IGF1-dependent growth in mice. AB - BACKGROUND: Haploinsufficiency of the FOXL2 transcription factor in humans causes Blepharophimosis/Ptosis/Epicanthus Inversus syndrome (BPES), characterized by eyelid anomalies and premature ovarian failure. Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis. We report here that mice lacking Foxl2 also show defects in postnatal growth and embryonic bone and cartilage formation. METHODS: Foxl2 (-/-) male mice at different stages of development have been characterized and compared to wild type. Body length and weight were measured and growth curves were created. Skeletons were stained with alcian blue and/or alizarin red. Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-FOXL2 and anti-SOX9 antibodies followed by confocal microscopy. Genes differentially expressed in skull vaults were evaluated by microarray analysis. Analysis of the GH/IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR. RESULTS: Compared to wild-type, Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization, with down-regulation of the GH/IGF1 axis. Consistent with these effects, we find FOXL2 expressed in embryos at 9.5 dpc in neural tube epithelium, in head mesenchyme near the neural tube, and within the first branchial arch; then, starting at 12.5 dpc, expressed in cartilaginous tissue; and at PO and P7, in hypothalamus. CONCLUSIONS: Our results support FOXL2 as a master transcription factor in a spectrum of developmental processes, including growth, cartilage and bone formation. Its action overlaps that of SOX9, though they are antagonistic in female vs male gonadal sex determination but conjoint in cartilage and skeletal development. PMID- 26134415 TI - Perceptual blurring and recognition memory: A desirable difficulty effect revealed. AB - Recent research in the area of desirable difficulty--defined as processing difficulty at either encoding or retrieval that improves long-term retention--has demonstrated that perceptually blurring an item makes processing less fluent, but does not improve remembering (Yue et al., 2013). This result led us to examine more closely perceptual blurring as a potential desirable difficulty. In Experiment 1, better recognition of blurry than clear words was observed, a result that contrasts with those reported by Yue et al. This result was replicated in Experiment 2, in which both mixed-list and pure-list designs were used. The following experiments were conducted to determine when blurring does and does not result in enhanced remembering. The desirable difficulty effect observed in Experiments 1 and 2 was replicated in Experiments 3A, 3B, and 3C, despite varying encoding intent during study, context reinstatement at the time of test, study list length, and the nature of the distractor task between study and test phases. It was only in Experiments 4A and 4B that a null effect of perceptual blurring on remembering was found. These experiments demonstrated that (1) the level of blurring used is critical, with a lower blurring level producing results similar to Yue et al. (2013), and (2) the introduction of judgments of learning at the time of study eliminated the benefit of blurring on remembering. These results extend the desirable difficulty principle to encoding manipulations involving perceptual blurring, and identify judgments of learning at encoding as a powerful moderator of this particular desirable difficulty effect. PMID- 26134416 TI - Hepatic denervation and dyslipidemia in obese Zucker (fa/fa) rats. AB - Human and animal studies increasingly point toward a neural pathogenesis of the metabolic syndrome, involving hypothalamic and autonomic nervous system dysfunction. We hypothesized that increased very-low-density lipoprotein triglyceride (VLDL-TG) secretion by the liver in a rat model for dyslipidemia, that is, the obese Zucker (fa/fa) rat, is due to relative hyperactivity of sympathetic, and/or hypoactivity of parasympathetic hepatic innervation. To test the involvement of the autonomic nervous system, we surgically denervated the sympathetic or parasympathetic hepatic nerve in obese Zucker rats. Our results show that cutting the sympathetic hepatic nerve lowers VLDL-TG secretion in obese rats, finally resulting in lower plasma TG concentrations after 6 weeks. In contrast, a parasympathetic denervation results in increased plasma total cholesterol concentrations. The effect of a sympathetic or parasympathetic denervation of the liver was independent of changes in humoral factors or changes in body weight or food intake. In conclusion, a sympathetic denervation improves the lipid profile in obese Zucker rats, whereas a parasympathetic denervation increases total cholesterol levels. We believe this is a novel treatment target, which should be further investigated. PMID- 26134417 TI - The 2014 liver ultrasound tracking benchmark. AB - The Challenge on Liver Ultrasound Tracking (CLUST) was held in conjunction with the MICCAI 2014 conference to enable direct comparison of tracking methods for this application. This paper reports the outcome of this challenge, including setup, methods, results and experiences. The database included 54 2D and 3D sequences of the liver of healthy volunteers and tumor patients under free breathing. Participants had to provide the tracking results of 90% of the data (test set) for pre-defined point-landmarks (healthy volunteers) or for tumor segmentations (patient data). In this paper we compare the best six methods which participated in the challenge. Quantitative evaluation was performed by the organizers with respect to manual annotations. Results of all methods showed a mean tracking error ranging between 1.4 mm and 2.1 mm for 2D points, and between 2.6 mm and 4.6 mm for 3D points. Fusing all automatic results by considering the median tracking results, improved the mean error to 1.2 mm (2D) and 2.5 mm (3D). For all methods, the performance is still not comparable to human inter-rater variability, with a mean tracking error of 0.5-0.6 mm (2D) and 1.2-1.8 mm (3D). The segmentation task was fulfilled only by one participant, resulting in a Dice coefficient ranging from 76.7% to 92.3%. The CLUST database continues to be available and the online leader-board will be updated as an ongoing challenge. PMID- 26134418 TI - Microarray based analysis of gene regulation by microRNA in intervertebral disc degeneration. AB - The present study aimed to explore the underlying mechanism of the development of intervertebral disc degeneration (IDD) by bioinformatics based on microarray datasets. GSE 19943 and GSE 34095 datasets downloaded from Gene Expression Omnibus data were used to screen the differentially expressed genes (DEGs) in IDD. The correlation between microRNAs and target genes was investigated using different algorithms. The underlying molecular mechanisms of the target genes were then explored using Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology function enrichment analysis. A total of 9 differentially expressed microRNAs, including 3 down- and 6 upregulated microRNAs and 850 DEGs were identified in tissue from patients with IDD. Two regulation networks of the target genes by microRNAs were constructed, including 33 upregulated microRNA target gene pairs and 4 downregulated microRNA-target gene pairs. Certain target genes had been demonstrated to be involved in IDD progression via various pathways, including in the cell cycle and pathways in cancer. In addition, two important microRNAs (microRNA-222 and microRNA-589) were identified that were pivotal for the development of IDD, and their target genes, CDKNAB and SMAD4. In conclusion, a comprehensive miRNA-target gene regulatory network was constructed, which was found to be important in IDD progression. PMID- 26134420 TI - Nano-sized Superlattice Clusters Created by Oxygen Ordering in Mechanically Alloyed Fe Alloys. AB - Creating and maintaining precipitates coherent with the host matrix, under service conditions is one of the most effective approaches for successful development of alloys for high temperature applications; prominent examples include Ni- and Co-based superalloys and Al alloys. While ferritic alloys are among the most important structural engineering alloys in our society, no reliable coherent precipitates stable at high temperatures have been found for these alloys. Here we report discovery of a new, nano-sized superlattice (NSS) phase in ball-milled Fe alloys, which maintains coherency with the BCC matrix up to at least 913 degrees C. Different from other precipitates in ferritic alloys, this NSS phase is created by oxygen-ordering in the BCC Fe matrix. It is proposed that this phase has a chemistry of Fe3O and a D03 crystal structure and becomes more stable with the addition of Zr. These nano-sized coherent precipitates effectively double the strength of the BCC matrix above that provided by grain size reduction alone. This discovery provides a new opportunity for developing high-strength ferritic alloys for high temperature applications. PMID- 26134419 TI - Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator. AB - Ferric uptake regulator (Fur) plays a key role in the iron homeostasis of prokaryotes, such as bacterial pathogens, but the molecular mechanisms and structural basis of Fur-DNA binding remain incompletely understood. Here, we report high-resolution structures of Magnetospirillum gryphiswaldense MSR-1 Fur in four different states: apo-Fur, holo-Fur, the Fur-feoAB1 operator complex and the Fur-Pseudomonas aeruginosa Fur box complex. Apo-Fur is a transition metal ion independent dimer whose binding induces profound conformational changes and confers DNA-binding ability. Structural characterization, mutagenesis, biochemistry and in vivo data reveal that Fur recognizes DNA by using a combination of base readout through direct contacts in the major groove and shape readout through recognition of the minor-groove electrostatic potential by lysine. The resulting conformational plasticity enables Fur binding to diverse substrates. Our results provide insights into metal ion activation and substrate recognition by Fur that suggest pathways to engineer magnetotactic bacteria and antipathogenic drugs. PMID- 26134421 TI - Vacuolar-ATPase-mediated intracellular sequestration of ellipticine contributes to drug resistance in neuroblastoma cells. AB - Neuroblastoma is the most common cancer in infants and the fourth most common cancer in children. Aggressive cell growth and chemoresistance are notorious obstacles in neuroblastoma therapy. Exposure to the anticancer drug ellipticine inhibits efficiently growth of neuroblastoma cells and induces apoptosis in these cells. However, ellipticine induced resistance in these cells. The upregulation of a vacuolar (V)-ATPase gene is one of the factors associated with resistance development. In accordance with this finding, we found that levels of V-ATPase protein expression are higher in the ellipticine-resistant UKF-NB-4ELLI line than in the parental ellipticine-sensitive UKF-NB-4 cell line. Treatment of ellipticine-sensitive UKF-NB-4 and ellipticine-resistant UKF-NB-4ELLI cells with ellipticine-induced cytoplasmic vacuolization and ellipticine is concentrated in these vacuoles. Confocal microscopy and staining of the cells with a lysosomal marker suggested these vacuoles as lysosomes. Transmission electron microscopy and no effect of an autophagy inhibitor wortmannin ruled out autophagy. Pretreatment with a V-ATPase inhibitor bafilomycin A and/or the lysosomotropic drug chloroquine prior to ellipticine enhanced the ellipticine-mediated apoptosis and decreased ellipticine-resistance in UKF-NB-4ELLI cells. Moreover, pretreatment with these inhibitors increased formation of ellipticine-derived DNA adducts, one of the most important DNA-damaging mechanisms responsible for ellipticine cytotoxicity. In conclusion, resistance to ellipticine in the tested neuroblastoma cells is associated with V-ATPase-mediated vacuolar trapping of this drug, which may be decreased by bafilomycin A and/or chloroquine. PMID- 26134423 TI - Spiers Memorial Lecture. New tools for observing the growth and assembly of colloidal inorganic nanocrystals. AB - We present two examples of the use of liquid cells to study colloidal inorganic nanocrystals using in situ transmission electron microscopy. The first uses a liquid cell to quantify the interaction potential between pairs of colloidal nanocrystals, and the second demonstrates direct imaging of nanocrystal growth and structure in the liquid cell. PMID- 26134424 TI - Ruscogenin suppresses mouse neutrophil activation: Involvement of protein kinase A pathway. AB - Ruscogenin, a natural steroidal sapogenin, presents in both food and medicinal plants. It has been found to exert significant anti-inflammatory activities. Considering that activation of neutrophil is a key feature of inflammatory diseases, this study was performed to investigate the inhibitory effect of ruscogenin and its underlying mechanisms responsible for neutrophil activation. Ruscogenin displayed potent antioxidative effects against Formyl-Met-Leu-Phe (FMLP)-induced extra- and intracellular superoxide generation in mouse bone marrow neutrophils, with IC50 values of 1.07+/-0.32 MUM and 1.77+/-0.46 MUM, respectively. Phorbol myristate acetate (PMA)-elicited extra- and intracellular superoxide generation were also suppressed by ruscogenin, with IC50 values of 1.56+/-0.46 MUM and 1.29+/-0.49 MUM, respectively. However, ruscogenin showed weak inhibition in NaF-induced response. Inhibition of superoxide generation was mediated neither by a superoxide-scavenging ability nor by a cytotoxic effect. Furthermore, ruscogenin inhibited the membrane translocation of p47phox and p67phox. It reduced FMLP-induced phosphorylation of cytosolic phospholipase A2 (cPLA2) and p21-activated kinase (PAK). The cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were increased by ruscogenin. Moreover, ruscogenin inhibited phosphorylation of protein kinase B (Akt), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal regulated kinase 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK). In addition, the inhibitory effects of ruscogenin on superoxide production and the phosphorylation of Akt, p38MAPK, and ERK1/2 were reversed by PKA inhibitor (H89), suggesting a PKA-dependent mechanism. In summary, our data suggest that ruscogenin inhibits activation of neutrophil through cPLA2, PAK, Akt, MAPKs, cAMP, and PKA signaling pathways. Increased PKA activity is associated with suppression of the phosphorylation of Akt, p38MAPK, and ERK1/2 pathways. PMID- 26134422 TI - Genome Wide Binding Site Analysis Reveals Transcriptional Coactivation of Cytokinin-Responsive Genes by DELLA Proteins. AB - The ability of plants to provide a plastic response to environmental cues relies on the connectivity between signaling pathways. DELLA proteins act as hubs that relay environmental information to the multiple transcriptional circuits that control growth and development through physical interaction with transcription factors from different families. We have analyzed the presence of one DELLA protein at the Arabidopsis genome by chromatin immunoprecipitation coupled to large-scale sequencing and we find that it binds at the promoters of multiple genes. Enrichment analysis shows a strong preference for cis elements recognized by specific transcription factor families. In particular, we demonstrate that DELLA proteins are recruited by type-B ARABIDOPSIS RESPONSE REGULATORS (ARR) to the promoters of cytokinin-regulated genes, where they act as transcriptional co activators. The biological relevance of this mechanism is underpinned by the necessity of simultaneous presence of DELLAs and ARRs to restrict root meristem growth and to promote photomorphogenesis. PMID- 26134425 TI - Dehydroepiandrosterone and 7-oxo-dehydroepiandrosterone in male reproductive health: Implications of differential regulation of human Sertoli cells metabolic profile. AB - Dehydroepiandrosterone (DHEA) is a precursor of androgen synthesis whose action is partially exerted through its metabolites. 7-Oxo-dehydroepiandrosterone (7-oxo DHEA) is a common DHEA metabolite, non-convertible to androgens, which constitutes a promising therapeutic strategy for multiple conditions. Sertoli cells (SCs) are responsible for the support of spermatogenesis, having unique metabolic characteristics strongly modulated by androgens. Consequently, disruptions in androgen synthesis compromise SCs function and hence male fertility. We aimed to evaluate the effects of DHEA and 7-oxo-DHEA in human SCs (hSCs) metabolism and oxidative profile. To do so, hSCs were exposed to increasing concentrations of DHEA and 7-oxo-DHEA (0.025, 1 and 50 MUM) that revealed to be non-cytotoxic in these experimental conditions. We measured hSCs metabolites consumption/production by (1)H NMR, the protein expression levels of key players of the glycolytic pathway by Western blot as well as the levels of carbonyl groups, nitration and lipid peroxidation by Slot blot. The obtained data demonstrated that 7-oxo-DHEA is a more potent metabolic modulator than DHEA since it increased hSCs glycolytic flux. DHEA seem to redirect hSCs metabolism to the Krebs cycle, while 7-oxo-DHEA has some inhibitory effect in this path. The highest 7-oxo-DHEA concentrations (1 and 50 MUM) also increased lactate production, which is of extreme relevance for the successful progression of spermatogenesis in vivo. None of these steroids altered the intracellular oxidative profile of hSCs, illustrating that, at the concentrations used they do not have pro- nor antioxidant actions in hSCs. Our study represents a further step in the establishment of safe doses of DHEA and 7-oxo-DHEA to hSCs, supporting its possible use in hormonal and non-hormonal therapies against male reproductive problems. PMID- 26134426 TI - Effects of estradiol, estrogen receptor subtype-selective agonists and genistein on glucose metabolism in leptin resistant female Zucker diabetic fatty (ZDF) rats. AB - The leptin resistant Zucker diabetic fatty (ZDF) rats are hyperphagic and become obese, but whereas the males develop type 2 diabetes mellitus (T2DM), the females remain euglycaemic. As estrogen deficiency is known to increase the risk of developing T2DM, we evaluated the role of ER subtypes alpha and beta in the development of glucose tolerance in leptin resistant ovariectomized (OVX) ZDF rats. At least six rats per group were treated with either vehicle (OVX), 17beta estradiol (E2), ER subtype-selective agonists (Alpha and Beta), or genistein (Gen) for 17 weeks. At the end of the treatment period a glucose tolerance assay was performed and the metabolic flux of (13)C-glucose for the E2 group was investigated. OVX ZDF rats treated with E2, Alpha, Beta, and Gen tolerated the glucose significantly better than untreated controls. E2 treatment increased absorbance/flux of (13)C-glucose to metabolic relevant tissues such liver, adipose tissue, gastrocnemius, and soleus muscle. Moreover, whereas Alpha treatment markedly increased mRNA expression of GLUT4 in gastrocnemius muscle, Beta treatment resulted in the largest fiber sizes of the soleus muscle. Treatment with Gen increased both the mRNA expression of GLUT 4 and the fiber sizes in the skeletal muscle. In addition, E2 and Alpha treatment decreased food intake and body weight gain. In summary, estrogen-improved glucose absorption is mediated via different molecular mechanisms: while activation of ER alpha seems to stimulate muscular GLUT4 functionality, activation of ER beta results in a hypertrophy of muscle fibers. In addition, selective activation of ER alpha decreased food intake and body weight gain. Our data further indicate that ER subtype-selective agonists and genistein improve systemic glucose tolerance also in the absence of a functional leptin signaling pathway. PMID- 26134427 TI - Predictors of Nonelective Removal of Peripherally Inserted Central Catheters in Infants. AB - BACKGROUND: Nonelective removal of peripherally inserted central catheters (PICCs) due to complications continues to be a major concern in neonatal intensive care units (NICUs) around the world. Nonelective removal results in interruption of intravenous therapy, added costs, stress, and negative impacts on infant's health. Identification of predictors of complications that lead to nonelective removal of PICCs would allow for the initiation of preventive strategies to improve the quality of care. AIM: To identify predictors of nonelective removal of PICCs in neonates. METHODS: A prospective cohort study with a sample of 524 PICC lines inserted in 436 neonates admitted to a tertiary level NICU of a Brazilian hospital. Data were collected on all neonates between August 31, 2010, and August 30, 2012. Neonates were monitored daily from insertion of the catheter until its removal. Bivariate analysis and a logistic regression were conducted in order to identify predictors of nonelective removal. RESULTS: A diagnosis of a transitory metabolic disorder (hypoglycemia; disorders of calcium, magnesium, sodium, or potassium; or dehydration), previous PICC line insertion, insertion of dual-lumen polyurethane PICC, noncentral tip position, and multiple intravenous solutions in a single-lumen silicone PICC were predictors of nonelective removal of PICC lines. CONCLUSION: The avoidance of repeated PICC insertions, noncentral tip position, and placement of single-lumen silicone PICCs for administration of four or more intravenous solutions is suggested. Interventions should be explored that facilitate PICC insertion success and correct tip placement. PMID- 26134428 TI - Nitric Oxide, Inflammation, Lipid Profile, and Cortisol in Normal- and Overweight Women With Fibromyalgia. AB - OBJECTIVES: Research has identified many factors associated with fibromyalgia (FM), but findings have been inconsistent. This study aimed to investigate changes in levels of nitric oxide (NO), inflammatory markers, lipid profile, and cortisol in normal- and overweight patients with FM and controls. Since most patients with FM are overweight, we explored possible changes in these markers according to body mass index (BMI). METHODS: This preliminary study was performed on serum samples of women with FM and age-matched controls, grouped according to their BMI: 12 normal-weight patients and 12 controls and 13 overweight patients and 8 controls. Ozone-based chemiluminescence assay was used to measure NO. Inflammatory mediators and cortisol were determined by immunoassay. Lipid profile was measured by a spectrophotometric procedure. Functional capacity was assessed by the fibromyalgia impact questionnaire (FIQ). RESULTS: Normal-weight patients showed higher levels of C-reactive protein (CRP) and apolipoprotein B compared to controls (both p < .05). CRP, apolipoprotein B, and triglycerides were higher in overweight patients versus overweight controls (all p < .05) and in overweight versus normal-weight patients (CRP p < .01; apolipoprotein B, triglycerides p < .05). The other markers were unaffected. Apolipoprotein B (r = .762; p < .05) and NO (r = -.921; p < .05) levels correlated with FIQ score in normal-weight patients. CRP level correlated with FIQ (r = .912; p < .05) in overweight patients. CONCLUSIONS: CRP and apolipoprotein B, biomarkers linked to cardiovascular events, may be associated with FM-related dysfunction in normal- and overweight women with FM. Their increased levels in these patients may indicate an increased risk of cardiovascular disease. PMID- 26134429 TI - Mixtures of multivariate power exponential distributions. AB - An expanded family of mixtures of multivariate power exponential distributions is introduced. While fitting heavy-tails and skewness have received much attention in the model-based clustering literature recently, we investigate the use of a distribution that can deal with both varying tail-weight and peakedness of data. A family of parsimonious models is proposed using an eigen-decomposition of the scale matrix. A generalized expectation-maximization algorithm is presented that combines convex optimization via a minorization-maximization approach and optimization based on accelerated line search algorithms on the Stiefel manifold. Lastly, the utility of this family of models is illustrated using both toy and benchmark data. PMID- 26134430 TI - Clinical and biological markers of difficult-to-treat severe chronic rhinosinusitis. AB - Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the upper airways of which two major phenotypes exist, CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). Some patients with CRS have suboptimal response to current guideline treatments. These patients remain severe and uncontrolled by treatment and have a poor quality of life. It is highly important to identify both clinical and biological markers, so-called biomarkers, in this subset of patients. The presence of nasal polyps and comorbidity with asthma and with aspirin-exacerbated respiratory disease (AERD) are the most common clinical traits that have been associated to difficult-to-treat severe CRS. In addition to clinical traits, numerous biological markers, with known etiopathogenic roles in CRS, have been associated to difficult-to-treat or recalcitrant CRS. This review summarizes the existing knowledge of the clinical and biological markers associated to difficult-to-treat or uncontrolled severe CRS. PMID- 26134432 TI - Gastrojejunocolic fistula as a cause of hypoalbuminemia and bilateral leg edema. PMID- 26134431 TI - Severe asthma in school-age children: evaluation and phenotypic advances. AB - Although the majority of children with asthma have a favorable clinical response to treatment with low to moderate doses of inhaled corticosteroids (ICS), a small subset of children have "severe" asthma characterized by ongoing symptoms and airway inflammation despite treatment with high doses of ICS and even oral corticosteroids. Although there is symptom heterogeneity in the affected children, children with severe asthma share the risk for adverse outcomes, including recurrent and potentially life-threatening exacerbations, which contribute to substantial economic burden. This article reviews current knowledge of severe asthma in school-age children (age 6-17 years) with a focus on recent literature published after January 2012. Clinical management approaches for children with severe asthma are discussed as well as current phenotyping efforts and emerging phenotypic-directed therapies that may be of benefit for subpopulations of children with severe asthma in the future. PMID- 26134433 TI - Bleeding from portal biliopathy in situs inversus totalis. PMID- 26134434 TI - Adenocarcinoma arising from ectopic gastric mucosa in an esophageal inlet patch: treatment by endoscopic submucosal dissection. PMID- 26134435 TI - Keep the fire burning: Current avenues in the quest of treating mitochondrial disorders. AB - Mitochondrial diseases are very heterogeneous in their genetic cause and clinical manifestation. During the last few decades progress has been made in the diagnosis of mitochondrial diseases, but an established therapy is so far lacking. Several experimental strategies targeting different points of intervention are currently being assessed world-wide. Numerous mouse models of OXPHOS disorders have become available enabling further optimization and validation of therapeutic strategies and paving the way for future clinical trials. In this review, we provide an update on current developments towards treatment as well as the potential and status of transition into therapeutic use. PMID- 26134436 TI - Heat-Denatured Lysozyme Inactivates Murine Norovirus as a Surrogate Human Norovirus. AB - Human norovirus infects humans through the consumption of contaminated food, contact with the excrement or vomit of an infected person, and through airborne droplets that scatter the virus through the air. Being highly infectious and highly viable in the environment, inactivation of the norovirus requires a highly effective inactivating agent. In this study, we have discovered the thermal denaturing capacity of a lysozyme with known antimicrobial activity against gram positive bacteria, as well as its inactivating effect on murine norovirus. This study is the first report on the norovirus-inactivating effects of a thermally denatured lysozyme. We observed that lysozymes heat-treated for 40 min at 100 degrees C caused a 4.5 log reduction in infectivity of norovirus. Transmission electron microscope analysis showed that virus particles exposed to thermally denatured lysozymes were expanded, compared to the virus before exposure. The amino acid sequence of the lysozyme was divided into three sections and the peptides of each artificially synthesised, in order to determine the region responsible for the inactivating effect. These results suggest that thermal denaturation of the lysozyme changes the protein structure, activating the region responsible for imparting an inactivating effect against the virus. PMID- 26134437 TI - Step-and-Shoot IMRT by Siemens Beams: An EPID Dosimetry Verification During Treatment. AB - PURPOSE: This work reports the extension of a semiempirical method based on the correlation ratios to convert electronic portal imaging devices transit signals into in vivo doses for the step-and-shoot intensity-modulated radiotherapy Siemens beams. The dose reconstructed at the isocenter point Diso, compared to the planned dose, Diso,TPS, and a gamma-analysis between 2-dimensional electronic portal imaging device images obtained day to day, seems to supply a practical method to verify the beam delivery reproducibility. METHOD: The electronic portal imaging device images were obtained by the superposition of many segment fields, and the algorithm for the Diso reconstruction for intensity-modulated radiotherapy step and shoot was formulated using a set of simulated intensity modulated radiotherapy beams. Moreover, the in vivo dose-dedicated software was integrated with the record and verify system of the centers. RESULTS: Three radiotherapy centers applied the in vivo dose procedure at 30 clinical intensity modulated radiotherapy treatments, each one obtained with 5 or 7 beams, and planned for patients undergoing radiotherapy for prostatic tumors. Each treatment beam was checked 5 times, obtaining 900 tests of the ratios R = Diso/Diso,TPS. The average R value was equal to 1.002 +/- 0.056 (2 standard deviation), while the mean R value for each patient was well within 5%, once the causes of errors were removed. The gamma-analysis of the electronic portal imaging device images, with 3% 3 mm acceptance criteria, showed 90% of the tests with Pgamma < 1 >= 95% and gammamean <= 0.5. The off-tolerance tests were found due to incorrect setup or presence of morphological changes. This preliminary experience shows the great utility of obtaining the in vivo dose results in quasi real time and close to the linac, where the radiotherapy staff may immediately spot possible causes of errors. The in vivo dose procedure presented here is one of the objectives of a project, for the development of practical in vivo dose procedures, financially supported by the Istituto Nazionale di Fisica Nucleare. PMID- 26134439 TI - A triazine di(carboxy)porphyrin dyad versus a triazine di(carboxy)porphyrin triad for sensitizers in DSSCs. AB - Two porphyrin-chromophores, i.e. triad PorZn-(PorCOOH)(2)-(piper)2 (GZ-T1) and dyad (PorZn)(2)-NMe2 (GZ-T1), have been synthesized and their photophysical and electrochemical properties have been investigated. The optical properties together with the appropriate electronic energy levels, i.e. the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels, revealed that both porphyrin assemblies can function as sensitizers for dye sensitized solar cells (DSSCs). The and -based DSSCs have been prepared and studied using 20 mM CDCA as coadsorbent and were found to exhibit an overall power conversion efficiency (PCE) of 5.88% and 4.56%, respectively (under an illumination intensity of 100 mW cm(-2) with TiO(2) films of 12 MUm). The higher PCE of the -sensitized DSSC, as revealed from the current voltage characteristic under illumination and the incident photon to current conversion efficiency (IPCE) spectra of the two DSSCs, is mainly attributed to its enhanced short circuit current (J(sc)), although both the open circuit voltage (V(oc)) and the fill factor are improved too. The electrochemical impedance spectra (EIS) demonstrated a shorter electron transport time, longer electron lifetime and higher charge recombination resistance for the DSSC sensitized with the dye as well as a larger dye loading onto the TiO(2) surface. PMID- 26134438 TI - Assessment of Treatment Response With Diffusion-Weighted MRI and Dynamic Contrast Enhanced MRI in Patients With Early-Stage Breast Cancer Treated With Single-Dose Preoperative Radiotherapy: Initial Results. AB - Single-dose preoperative stereotactic body radiotherapy is a novel radiotherapy technique for the early-stage breast cancer, and the treatment response pattern of this technique needs to be investigated on a quantitative basis. In this work, dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted magnetic resonance imaging were used to study the treatment response pattern in a unique cohort of patients with early-stage breast cancer treated with preoperative radiation. Fifteen female qualified patients received single-dose preoperative radiotherapy with 1 of the 3 prescription doses: 15 Gy, 18 Gy, and 21 Gy. Magnetic resonance imaging scans including both diffusion-weighted magnetic resonance imaging and dynamic contrast-enhanced magnetic resonance imaging were acquired before radiotherapy for planning and after radiotherapy but before surgical resection. In diffusion-weighted magnetic resonance imaging, the regional averaged apparent diffusion coefficient was calculated. In dynamic contrast-enhanced magnetic resonance imaging, quantitative parameters K (trans) and v e were evaluated using the standard Tofts model based on the average contrast agent concentration within the region of interest, and the semiquantitative initial area under the concentration curve (iAUC6min) was also recorded. These parameters' relative changes after radiotherapy were calculated for gross tumor volume, clinical target volume, and planning target volume. The initial results showed that after radiotherapy, initial area under the concentration curve significantly increased in planning target volume (P < .006) and clinical target volume (P < .006), and v e significantly increased in planning target volume (P < .05) and clinical target volume (P < .05). Statistical studies suggested that linear correlations between treatment dose and the observed parameter changes exist in most examined tests, and among these tests, the change in gross tumor volume regional averaged apparent diffusion coefficient (P < .012) and between treatment dose and planning target volume K (trans) (P < .029) were found to be statistically significant. Although it is still preliminary, this pilot study may be useful to provide insights for future works. PMID- 26134440 TI - Safety of topotecan monotherapy for relapsed small cell lung cancer patients with pre-existing interstitial lung disease. AB - PURPOSE: To investigate the safety of intravenous topotecan monotherapy for relapsed small cell lung cancer (SCLC) patients with pre-existing interstitial lung disease (ILD). METHODS: A total of 77 patients who received topotecan for the treatment of relapsed SCLC between April 2007 and April 2014 were reviewed. Patients with pre-existing ILD were identified using the pretreatment chest computed tomography. The safety of intravenous topotecan for SCLC patients with ILD was retrospectively examined, particularly focusing on topotecan-induced acute exacerbation of ILD (AE-ILD). RESULTS: Twenty-three patients were identified as having pre-existing ILD [median age 74 (range 55-85) years; 21 men]. At the first topotecan administration, two-thirds (65.2%) had an Eastern Cooperative Oncology Group performance status 0 or 1. Topotecan was administered intravenously as second-line (n = 11) or later chemotherapy (n = 12). The median number of treatment cycles was two (range 1-7). The most common adverse events with grade 3 or 4 were neutropenia in 13 patients (56.5%) and thrombocytopenia in 10 patients (43.5%). Febrile neutropenia was observed in six patients (26.1%) and resulted in one death. AE-ILD occurred in five patients (21.7%; 95% confidence interval 4.9-38.5 %) 5-18 days after the last administration of topotecan and was fatal in three cases. CONCLUSIONS: Intravenous topotecan monotherapy can be unsafe for relapsed SCLC patients with pre-existing ILD. Clinicians should be cautious regarding topotecan-induced AE-ILD as a lethal complication. PMID- 26134444 TI - Controversies in total knee arthroplasty: Cochrane evidence or surgeons' philosophy? PMID- 26134441 TI - Preferential recruitment of the maternal centromere-specific histone H3 (CENH3) in oat (Avena sativa L.) * pearl millet (Pennisetum glaucum L.) hybrid embryos. AB - Chromosome elimination occurs frequently in interspecific hybrids between distantly related species in Poaceae. However, chromosomes from both parents behave stably in a hybrid of female oat (Avena sativa L.) pollinated by pearl millet (Pennisetum glaucum L.). To analyze the chromosome behavior in this hybrid, we cloned the centromere-specific histone H3 (CENH3) genes of oat and pearl millet and produced a pearl millet-specific anti-CENH3 antibody. Application of this antibody together with a grass species common anti-CENH3 antibody revealed the dynamic CENH3 composition of the hybrid cells before and after fertilization. Despite co-expression of CENH3 genes encoded by oat and pearl millet, only an oat-type CENH3 was incorporated into the centromeres of both species in the hybrid embryo. Oat CENH3 enables a functional centromere in pearl millet chromosomes in an oat genetic background. Comparison of CENH3 genes among Poaceae species that show chromosome elimination in interspecific hybrids revealed that the loop 1 regions of oat and pearl millet CENH3 exhibit exceptionally high similarity. PMID- 26134445 TI - Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion. AB - DNA ligases are essential for the maintenance of genome integrity as they are indispensable for DNA replication, recombination and repair. The present study was undertaken to gain insights into the prevalence and clinical significance of ligase IV (LIG4) expression in prostate cancer. A total of 11,152 prostate cancer specimens were analyzed by immunohistochemistry for LIG4 expression. Results were compared to follow-up data, ERG status and deletions at PTEN, 3p13, 5q21 and 6q15. LIG4 expression was predominantly localized in the nucleus of the cells with increased intensities in malignant as compared to benign prostate epithelium. In prostate cancer, LIG4 expression was found in 91% of interpretable tumors, including 12% cancers with weak, 23% with moderate and 56% with strong LIG4 positivity. Strong LIG4 expression was tightly linked to advanced Gleason score (P<0.0001) and positive nodal involvement (P=0.03). There was a remarkable accumulation of strong LIG4 expression in tumors harboring TMPRSS2:ERG fusion and PTEN deletions (P<0.0001 each). High LIG4 expression was also tightly related to early biochemical recurrence when all tumors (P<0.0001) or the subsets of ERG negative (P=0.0004) or ERG-positive prostate cancers (P=0.006) were analyzed. Multivariate analysis including parameters that are available before surgery demonstrated independent association with biochemical recurrence for advanced Gleason grade on biopsy, high preoperative PSA level, high clinical stage (P<0.0001 each) and for LIG4 immunostaining (P=0.03). Our study identifies LIG4 as a predictor of an increased risk for early PSA recurrence in prostate cancer. Moreover, the strong association with TMPRSS2:ERG fusion and PTEN deletions suggest important interactions between these pathways in prostate cancers. PMID- 26134446 TI - Pancreaticoduodenectomy for distal cholangiocarcinoma: surgical results, prognostic factors, and long-term follow-up. AB - PURPOSE: Prognostic indicators for distal cholangiocarcinoma have not been widely confirmed because of its rarity. Despite the early appearance of symptoms, it has a very poor prognosis. The aim of this study was to identify prognostic factors in patients undergoing pancreaticoduodenectomy (PD) for distal bile duct cancer (DBDC) in a high-volume center for pancreatic disease. METHODS: From January 2000 to December 2013, 1490 PD were performed for periampullary disease. Data from all patients with histologically proven cholangiocarcinoma were reviewed. Preoperative data, post-operative complications, pathologic features, and survival were investigated. RESULTS: Among 50 histologically proven DBDC (3.3 %), 4 patients who underwent CBD resection were excluded. Thus, the study population consisted of 46 patients. Overall surgical morbidity rate was 67.4 %; mortality was nil. Major complications were pancreatic fistula (47.8 %), abdominal collections (34.8 %), post-pancreatectomy hemorrhage (21.7 %), and delayed gastric emptying (10.9 %). The majority of resections were R0 (73.9 %). The presence of metastatic lymph nodes (N1) was identified in 76.1 % of cases. Among N1 cases, the most frequently involved lymph nodes were pancreaticoduodenal nodes (50 %), hepatoduodenal ligament nodes (21.7 %), superior mesenteric artery nodes (8.7 %), and anterior hepatic artery nodes (4.3 %). Overall, survival rates were 88.8, 40, and 18 % at 1, 3, and 5 years, respectively. Median survival was 31 months. By univariate analysis, only tumor grading and nodal metastasis were predictors of poor prognosis (p < 0.05). These findings were not confirmed in multivariate analysis. CONCLUSIONS: This study shows that DBDC is a rare entity even if large surgical series are reviewed. Tumor differentiation and nodal status have been confirmed as important prognostic factors. Pancreaticoduodenectomy remains the procedure of choice in order to obtain free surgical margins and in order to harvest the correct number of lymph nodes for a correct staging. PMID- 26134447 TI - Nitrate removal from high strength nitrate-bearing wastes in granular sludge sequencing batch reactors. AB - A 6-L sequencing batch reactor (SBR) was operated for development of granular sludge capable of denitrification of high strength nitrates. Complete and stable denitrification of up to 5420 mg L(-1) nitrate-N (2710 mg L(-1) nitrate-N in reactor) was achieved by feeding simulated nitrate waste at a C/N ratio of 3. Compact and dense denitrifying granular sludge with relatively stable microbial community was developed during reactor operation. Accumulation of large amounts of nitrite due to incomplete denitrification occurred when the SBR was fed with 5420 mg L(-1) NO3-N at a C/N ratio of 2. Complete denitrification could not be achieved at this C/N ratio, even after one week of reactor operation as the nitrite levels continued to accumulate. In order to improve denitrification performance, the reactor was fed with nitrate concentrations of 1354 mg L(-1), while keeping C/N ratio at 2. Subsequently, nitrate concentration in the feed was increased in a step-wise manner to establish complete denitrification of 5420 mg L(-1) NO3-N at a C/N ratio of 2. The results show that substrate concentration plays an important role in denitrification of high strength nitrate by influencing nitrite accumulation. Complete denitrification of high strength nitrates can be achieved at lower substrate concentrations, by an appropriate acclimatization strategy. PMID- 26134448 TI - Facilitation of uniform maturation of human retinal pigment epithelial cells through collective movement in culture. AB - Understanding of the fundamental mechanisms that govern tight junction formation of retinal pigment epithelial (RPE) cells provides surface design strategies for promoting their maturation in culture. RPE cells were cultured to investigate their migratory behavior and the expression of tight junction protein ZO-1 in the central and peripheral regions of a culture vessel. Regardless of locational differences in the culture vessel, the cells at day 1 were elongated in shape, did not form tight junctions, and migrated actively. As the culture progressed, the cells in the central region slowly moved with morphological change of a cobblestone-like shape via interaction between contact cells and exhibiting the shift from random migration to collective movement toward the center, accompanied by tight junction formation. On the other hand, the cells in the peripheral region maintained the random migration at day 5, meaning spatial heterogeneity in maturation in the vessel. At day 5, RPE cells were incubated in medium with Rac1 inhibitor and the exposure to the Rac1 inhibitor triggered the rapid conversion of migratory behavior from random migration to collective movement toward the center of the vessel, resulting in uniform maturation. These findings indicate that the change in migratory patterns is an important cues and the collective movement toward the center causes the facilitation of uniform maturation in the vessel. PMID- 26134449 TI - Correction to "Stitched alpha-Helical Peptides via Bis Ring-Closing Metathesis". PMID- 26134450 TI - HLA-DQ genotypes - but not immune markers - differ by ethnicity in patients with childhood onset type 1 diabetes residing in Belgium. AB - AIM: The aim of this study was to compare genetic (HLA-DQ) and immune markers in a large population of type 1 diabetic (T1D) children and adolescents residing in the same environment, but of different ethnic origin: European Caucasians (EC), Moghrabin Caucasians (MC), Black Africans (BA) and of Mixed Origin (MO). METHODS: Retrospective study, including 452 patients with T1D aged 0.1-17.5 yr at diagnosis recruited at the Diabetology Clinic of the University Children's Hospital Queen Fabiola from May 1995 to March 2013. HLA-DQ genotyping, diabetes associated autoantibodies, organ-specific autoantibodies, and other markers of autoimmunity were studied. RESULTS: The proportion of the different ethnic groups was: 55% EC, 35% MC, 6% BA, and 4% MO. Between these four groups, there were no significant differences concerning age, hemoglobin A1c (HbA1c), presence of diabetic ketoacidosis, random C-peptide level at diagnosis and 2 yr later. The two most frequent haplotypes were DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302 with a significant higher prevalence in MC and EC (p = 0.002 and 0.03, respectively). The high-risk heterozygous genotype DQA1*0301-DQB1*0302/DQA1*0501 DQB1*0201 was more frequent in EC than in MC, whereas the homozygous genotype DQA1*0501-DQB1*0201/DQA1*0501-DQB1*0201 was more prevalent in MC (p = 0.019). These susceptible genotypes were more frequent in youngest patients (p = 0.003). Diabetes-associated autoantibodies, organ-specific autoantibodies, and other immune markers did not statistically differ between ethnic groups. CONCLUSIONS: These observations in a large population of T1D children and adolescents of different ethnic groups residing in Belgium show significant differences in HLA DQ status, but not in diabetes-associated autoantibodies, organ-specific autoantibodies, or other immune markers. PMID- 26134452 TI - Old is new again: a chemical probe for targeting mitochondria and monitoring mitochondrial membrane potential in cells. AB - Here, we explore the new application of an old molecule. We find that the tetraphenylethene-indolium molecule (TPE-indo) can both image the mitochondria (in the aggregated state), and indicate mitochondrial activity by the fluorescence change of TPE-indo. TPE-indo shows good photostability, longer emission wavelength, targeting effect for mitochondria, and better response to the changes of the mitochondrial membrane potential (DeltaPsim). PMID- 26134451 TI - PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies. AB - PURPOSE: Despite the promising applications of PLGA based particles, studies examining the fate and consequences of these particles after intra-articular administration in the joint are scanty. This study was carried out to evaluate the neutrality of the unloaded delivery system on different articular cell types. To facilitate tracking, we have thus developed a fluorescent core of particles, combined to a hyaluronate shell for cell recognition. METHODS: Fluorescence pictures were taken at time intervals to assess the internalization and the corresponding inflammatory response was monitored by RT-qPCR and biochemical measurements. After NPs pre-treatment, mesenchymal stem cells (MSCs) were cultured into chondrogenic, adipogenic or osteogenic differentiation media, to investigate if NPs exposure interferes with differentiation ability. Finally, intra-articular injections were performed in healthy rat knees and joint's structure analysed by histological studies. RESULTS: Particles were detected in cytoplasm 8 h after exposure. Internalization led to a slight and reversible increase of inflammatory markers, but lower than in inflammatory conditions. We have confirmed particles exposure minimal neutrality on MSCs pluripotency. Histological exams of joint after intra-articular injections do not demonstrate any side effects of NPs. CONCLUSIONS: Our findings suggest that such a delivery platform is well tolerated locally and could be used to deliver active molecules to the joint. PMID- 26134453 TI - Effect of ACL graft material on anterior knee force during simulated in vivo ovine motion applied to the porcine knee: An in vitro examination of force during 2000 cycles. AB - This study determined how anterior cruciate ligament (ACL) reconstruction affected the magnitude and temporal patterns of anterior knee force and internal knee moment during 2000 cycles of simulated gait. Porcine knees were tested using a six degree-of-freedom robot, examining three porcine allograft materials compared with the native ACL. Reconstructions were performed using: (1) bone patellar tendon-bone allograft (BPTB), (2) reconstructive porcine tissue matrix (RTM), or (3) an RTM-polymer hybrid construct (Hybrid). Forces and moments were measured over the entire gait cycle and contrasted at heel strike, mid stance, toe off, and peak flexion. The Hybrid construct performed the best, as magnitude and temporal changes in both anterior knee force and internal knee moment were not different from the native ACL knee. Conversely, the RTM knees showed greater loss in anterior knee force during 2000 cycles than the native ACL knee at heel strike and toe off, with an average force loss of 46%. BPTB knees performed the least favorably, with significant loss in anterior knee force at all key points and an average force loss of 61%. This is clinically relevant, as increases in post-operative knee laxity are believed to play a role in graft failure and early onset osteoarthritis. PMID- 26134454 TI - Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress. AB - Mycotoxins are considered to be significant contaminants of food and animal feed. Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. ZEN has been shown to be cytotoxic, genotoxic, and mutagenic in different cell types. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in ZEN-mediated toxicity in human intestine (HCT116) and kidney (HEK293) cells and evaluated the effects of the two common dietary compounds Quercetin (QUER) and Crocin (CRO). We show that ZEN treatment induces ER stress and activates the unfolded protein response (UPR) as evidenced by XBP1 mRNA splicing and upregulation of GRP78, ATF4, GADD34, PDIA6, and CHOP. Activation of the ER stress response is associated with activation of the mitochondrial pathway of apoptosis. This apoptotic process is characterized by an increase in ROS generation and lipid peroxidation, a loss of mitochondrial transmembrane potential (DeltaPsim), and an activation of caspases and DNA damages. We also demonstrate that the antioxidant properties of QUER and CRO help to prevent ER stress and reduce ZEN induced apoptosis in HCT116 and HEK293 cells. Our results suggest that antioxidant molecule might be helpful to prevent ZEN-induced ER stress and toxicity. PMID- 26134455 TI - Increased titer and reduced lactate accumulation in recombinant retrovirus production through the down-regulation of HIF1 and PDK. AB - Many mammalian cell lines used in the manufacturing of biopharmaceuticals exhibit high glycolytic flux predominantly channeled to the production of lactate. The accumulation of lactate in culture reduces cell viability and may also decrease product quality. In this work, we engineered a HEK 293 derived cell line producing a recombinant gene therapy retroviral vector, by down-regulating hypoxia inducible factor 1 (HIF1) and pyruvate dehydrogenase kinase (PDK). Specific productivity of infectious viral titers could be increased more than 20 fold for single gene knock-down (HIF1 or PDK) and more than 30-fold under combined down-regulation. Lactate production was reduced up to 4-fold. However, the reduction in lactate production, alone, was not sufficient to enhance the titer: high-titer clones also showed significant enrollment of metabolic routes not related to lactate production. Transcriptome analysis indicated activation of biological amines metabolism, detoxification routes, including glutathione metabolism, pentose phosphate pathway, glycogen biosynthesis and amino acid catabolism. The latter were validated by enzyme activity assays and metabolite profiling, respectively. High-titer clones also presented substantially increased transcript levels of the viral genes expression cassettes. The results herein presented demonstrate the impact of HIF1 and PDK down-regulation on the production performance of a mammalian cell line, reporting one of the highest fold-increase in specific productivity of infectious virus titers achieved by metabolic engineering. They additionally highlight the contribution of secondary pathways, beyond those related to lactate production, that can be also explored to pursue improved metabolic status favoring a high-producing phenotype. PMID- 26134456 TI - Chronic Hypoxia Increases Intracellular Ca(2+) Concentration via Enhanced Ca(2+) Entry Through Receptor-Operated Ca(2+) Channels in Pulmonary Venous Smooth Muscle Cells. AB - BACKGROUND: Hypoxic pulmonary hypertension (HPH) is characterized by pulmonary vascular remodeling. Intracellular Ca(2+)concentration ([Ca(2+)]i) is an essential signal for myocyte proliferation. Whether chronic hypoxia (CH) affects the basal [Ca(2+)]I and Ca(2+)entry through store- and/or receptor-operated calcium channels (SOCC, ROCC), and whether canonical transient receptor potential (TRPC) proteins are involved in CH-induced Ca(2+)influx and proliferation in pulmonary venous smooth muscle cells (PVSMCs) is examined. METHODS AND RESULTS: Rats were exposed to CH. PVSMCs were isolated from distal pulmonary veins. In freshly isolated PVSMCs, CH increased the basal [Ca(2+)]i; removal of Ca(2+)or application of SKF-96365 reversed the elevated [Ca(2+)]i, whereas nifedipine had no effect. Receptor-operated Ca(2+)entry (ROCE) was expressed in PVSMCs. In freshly isolated PVSMCs from CH rats, ROCE was enhanced, whereas store-operated Ca(2+)entry had no alteration. Furthermore, real-time polymerase chain reaction and western blotting showed that mRNA and protein expression level of TRPC6, but neither TRPC1 nor TRPC3, in pulmonary venous smooth muscle (PV) from CH rats and PVSMCs exposed to CH was greater than in normal PV and PVSMCs. The knockdown of TRPC6 in hypoxic PVSMCs with siRNA inhibited the enhanced ROCE and attenuated CH induced PVSMCs proliferation. CONCLUSIONS: The enhanced Ca(2+)entry through ROCC, due to upregulated TRPC6, is a novel pathogenic mechanism contributing to the increased basal [Ca(2+)]iin PVSMCs and excessive PVSMC proliferation during the development of HPH. PMID- 26134457 TI - Long-Term Clinical Outcomes of True and Non-True Bifurcation Lesions According to Medina Classification- Results From the COBIS (COronary BIfurcation Stent) II Registry. AB - BACKGROUND: Little is known about the clinical outcomes of patients with different types of coronary bifurcation lesions. We sought to compare long-term clinical outcomes of patients with true or non-true bifurcation lesions who underwent percutaneous coronary intervention. METHODS AND RESULTS: We compared major adverse cardiac events (MACE: cardiac death, myocardial infarction [MI], or target lesion revascularization) between 1,502 patients with true bifurcation lesions (51.8%) and 1,395 with non-true bifurcation lesions (48.2%). True bifurcation lesions were defined as Medina classification (1.1.1), (1.0.1), or (0.1.1) lesions. During a median follow-up of 36 months, MACE occurred in 296 (10.2%) patients. Patients with true bifurcation lesions had a significantly higher risk of MACE than those with non-true bifurcation lesions (HR 1.39; 95% CI 1.08-1.80; P=0.01). Among true bifurcation lesions, Medina (1.1.1) and (0.1.1) were associated with a higher risk of cardiac death or MI than Medina (1.0.1) (HR 4.15; 95% CI 1.01-17.1; P=0.05). During the procedure, side branch occlusion occurred more frequently in Medina (1.1.1) and (1.0.1) than Medina (0.1.1) lesions (11.5% vs. 7.4%, P=0.03). CONCLUSIONS: Patients with true bifurcation lesions had worse clinical outcomes than those with non-true bifurcation lesions. Procedural and long-term clinical outcomes differed according to the type of bifurcation lesion. These findings should be considered in future bifurcation studies. PMID- 26134458 TI - Land Use Regression Models of On-Road Particulate Air Pollution (Particle Number, Black Carbon, PM2.5, Particle Size) Using Mobile Monitoring. AB - Land Use Regression (LUR) models typically use fixed-site monitoring; here, we employ mobile monitoring as a cost-effective alternative for LUR development. We use bicycle-based, mobile measurements (~85 h) during rush-hour in Minneapolis, MN to build LUR models for particulate concentrations (particle number [PN], black carbon [BC], fine particulate matter [PM2.5], particle size). We developed and examined 1224 separate LUR models by varying pollutant, time-of-day, and method of spatial and temporal smoothing of the time-series data. Our base-case LUR models had modest goodness-of-fit (adjusted R(2): ~0.5 [PN], ~0.4 [PM2.5], 0.35 [BC], ~0.25 [particle size]), low bias (<4%) and absolute bias (2-18%), and included predictor variables that captured proximity to and density of emission sources. The spatial density of our measurements resulted in a large model building data set (n = 1101 concentration estimates); ~25% of buffer variables were selected at spatial scales of <100m, suggesting that on-road particle concentrations change on small spatial scales. LUR model-R(2) improved as sampling runs were completed, with diminishing benefits after ~40 h of data collection. Spatial autocorrelation of model residuals indicated that models performed poorly where spatiotemporal resolution of emission sources (i.e., traffic congestion) was poor. Our findings suggest that LUR modeling from mobile measurements is possible, but that more work could usefully inform best practices. PMID- 26134459 TI - beta-Tetrachlorotetramethoxyporphycenes: positional effect of substituents on structure and photophysical properties. AB - We report the regiospecific synthesis of the first chloro-substituted porphycenes as two positional isomers of beta-tetrachlorotetramethoxyporphycene. The positional effect of the substituents on these isomers could be clearly distinguished in their structure and photophysical properties. PMID- 26134460 TI - The emergence of extracellular vesicles in urology: fertility, cancer, biomarkers and targeted pharmacotherapy. AB - Extracellular vesicles (EV) are small membrane-bound vesicles enriched in a selective repertoire of mRNA, miRNA, proteins and cell surface receptors from parental cells and are actively involved in the transmission of inter and intracellular signals. Cancer cells produce EV that contain cargo including DNA, mRNA, miRNA and proteins that allow EV to create epigenetic changes in target cells both locally and systemically. Cancer-derived EV play critical roles in tumorigenesis, cancer cell migration, metastasis, evasion of host immune defense, chemoresistance, and they promote a premetastatic niche favourable to micrometastatic seeding. Their unique molecular profiles acquired from originator cells and their presence in numerous body fluids, including blood and urine, make them promising candidates as biomarkers for prostate, renal and bladder cancers. EV may ultimately serve as targets for therapy and as platforms for personalized medicine in urology. As urologic malignancy comprises 28% of new solid tumour diagnoses and 15% of cancer-related deaths, EV-related research is rapidly emerging and providing unique insights into disease progression. In this report, we review the current literature on EV in the setting of genitourinary fertility and malignancy. PMID- 26134461 TI - Okadaic acid is taken-up into the cells mediated by human hepatocytes transporter OATP1B3. AB - Okadaic acid is known as a diarrheal shellfish poison. It is thought that there is no specific target organ for okadaic acid after it has been absorbed into the body. However, the details of its pharmacokinetics are still unknown. In this study, we demonstrated that okadaic acid was more toxic to the hepatocyte specific uptake transporter OATP1B1- or OATP1B3-expressing cells than control vector-transfected cells. In addition, PP2A activity, which is a target molecule of okadaic acid, was more potently inhibited by okadaic acid in OATP1B1- or OATP1B3-expressing cells compared with control vector-transfected cells. The cytotoxicity of okadaic acid in OATP1B1- or OATP1B3-expressing cells was attenuated by known substrates of OATP1B1- and OATP1B3, but not in control vector transfected cells. Furthermore, after uptake inhibition study using OATP1B3 expressing cells, Dixon plot showed that okadaic acid inhibited the uptake of hepatotoxin microcystin-LR, which is a substrate for OATP1B1 and OATP1B3, in a competitive manner. These results strongly suggested that okadaic acid is a substrate for OATP1B3 and probably for OATP1B1, and could be involved in unknown caused liver failure and liver cancer. Since okadaic acid possesses cytotoxicity and cell proliferative activity by virtue of its known phosphatase inhibition activity. PMID- 26134462 TI - Improved oxygenation during standing performance of deep breathing exercises with positive expiratory pressure after cardiac surgery: A randomized controlled trial. AB - OBJECTIVE: Breathing exercises after cardiac surgery are often performed in a sitting position. It is unknown whether oxygenation would be better in the standing position. The aim of this study was to evaluate oxygenation and subjective breathing ability during sitting vs standing performance of deep breathing exercises on the second day after cardiac surgery. METHODS: Patients undergoing coronary artery bypass grafting (n = 189) were randomized to sitting (controls) or standing. Both groups performed 3 * 10 deep breaths with a positive expiratory pressure device. Peripheral oxygen saturation was measured before, directly after, and 15 min after the intervention. Subjective breathing ability, blood pressure, heart rate, and pain were assessed. RESULTS: Oxygenation improved significantly in the standing group compared with controls directly after the breathing exercises (p < 0.001) and after 15 min rest (p = 0.027). The standing group reported better deep breathing ability compared with controls (p = 0.004). A slightly increased heart rate was found in the standing group (p = 0.047). CONCLUSION: After cardiac surgery, breathing exercises with positive expiratory pressure, performed in a standing position, significantly improved oxygenation and subjective breathing ability compared with sitting performance. Performance of breathing exercises in the standing position is feasible and could be a valuable treatment for patients with postoperative hypoxaemia. PMID- 26134463 TI - Age determination in dogs using ocular light reflection, dental abrasion and tartar. AB - OBJECTIVE: The knowledge of an animal's age is important for disease probability, prognoses, or epidemiological questions, but unfortunately, it is often unknown for dogs in animal shelters. A simple estimating procedure is preferable being quick and easy to perform, even for non-veterinarians. MATERIAL AND METHODS: In 295 dogs the dimension of light reflection (diameter in millimetres), visible on the posterior lens capsule using a penlight, the grade of dental abrasion and dental tartar were documented photographically and the exact weight and age in days were obtained. These photographs were evaluated blinded. The dogs were divided randomly into two groups. The first group was used to establish a model for age determination using linear and logistic regression models considering the documented parameters, which was then validated with the data of the second group. RESULTS: The size of ocular light reflection and age correlated significantly (r = 0.781; p < 0.001; sy,x = 2.45 years [SD of y for given x]). The linear regression model gave the final equation: Estimated age [months] = 13.954 + 33.400 * lens reflection [mm] + 8.406 * dental abrasion [grade] + 8.871 * tartar [grade] with a standard error of estimation of 2.26 years. CONCLUSION AND CLINICAL RELEVANCE: Age determination, even based on three parameters results in a large standard deviation making age estimation in dogs very crude. PMID- 26134464 TI - The role of a structure directing agent tetramethylammonium template in the initial steps of silicate oligomerization in aqueous solution. AB - The understanding of the formation of silicate oligomers in the initial stage of zeolite synthesis is of fundamental scientific and technological importance. The use of different organic structure directing agents is known to be a key factor in the formation of different silicate species, and the final zeolite structure. Tetramethylammonium (TMA(+)), for example, is indispensable for the formation of the LTA zeolite type. However, the role of a TMA(+) template has not yet been elucidated at the molecular level. In this study, ab initio molecular dynamic simulations were combined with thermodynamic integration to arrive at an understanding of the role of TMA(+) in the formation of various silicate species, ranging from dimer to 4-ring. Free energy profiles show that trimer and 3-ring silicate are less favourable than other oligomers such as linear tetramer, branched tetramer and 4-ring structures. TMA(+) exhibits an important role in controlling the predominant species in solution via its coordination with silicate structures during the reaction process. This can explain that formation of D4R.8TMA crystals, as observed in experiment, is controlled by the single 4 ring formation step. PMID- 26134465 TI - Peripheral Nerve Repair: Multimodal Comparison of the Long-Term Regenerative Potential of Adipose Tissue-Derived Cells in a Biodegradable Conduit. AB - Tissue engineering is a popular topic in peripheral nerve repair. Combining a nerve conduit with supporting adipose-derived cells could offer an opportunity to prevent time-consuming Schwann cell culture or the use of an autograft with its donor site morbidity and eventually improve clinical outcome. The aim of this study was to provide a broad overview over promising transplantable cells under equal experimental conditions over a long-term period. A 10-mm gap in the sciatic nerve of female Sprague-Dawley rats (7 groups of 7 animals, 8 weeks old) was bridged through a biodegradable fibrin conduit filled with rat adipose-derived stem cells (rASCs), differentiated rASCs (drASCs), human (h)ASCs from the superficial and deep abdominal layer, human stromal vascular fraction (SVF), or rat Schwann cells, respectively. As a control, we resutured a nerve segment as an autograft. Long-term evaluation was carried out after 12 weeks comprising walking track, morphometric, and MRI analyses. The sciatic functional index was calculated. Cross sections of the nerve, proximal, distal, and in between the two sutures, were analyzed for re-/myelination and axon count. Gastrocnemius muscle weights were compared. MRI proved biodegradation of the conduit. Differentiated rat ASCs performed significantly better than undifferentiated rASCs with less muscle atrophy and superior functional results. Superficial hASCs supported regeneration better than deep hASCs, in line with published in vitro data. The best regeneration potential was achieved by the drASC group when compared with other adipose tissue-derived cells. Considering the ease of procedure from harvesting to transplanting, we conclude that comparison of promising cells for nerve regeneration revealed that particularly differentiated ASCs could be a clinically translatable route toward new methods to enhance peripheral nerve repair. PMID- 26134466 TI - A Geomimetic Approach to the Formation and Identification of Fossil Sterane Biomarkers in Crude Oil: 18-nor-D-homo-Androstane and 5alpha,14beta-Androstane. AB - A diazonium ion derived from 18-aminoandrostane rearranged upon decomposition by a carbonium and a carbenium ion to furnish a mixture of a cyclopropanated compound and two D-homo-androstenes. Hydrogenation of this mixture gave the saturated hydrocarbons, 18-nor-D-homo-androstane and 5alpha,14beta-androstane, which are both fossil sterane biomarkers in Neoproterozoic crude oil. The so far unknown constitution and configuration as well as the geochemical genesis were established by this experiment. The starting material for this investigation, 18 aminoandrostane, was prepared in twelve steps from androstan-17-one (12.5% overall yield) with a Barton reaction as the key step. PMID- 26134467 TI - Human T-lymphotropic virus type I proviral loads in patients with adult T-cell leukemia-lymphoma: Comparison between cutaneous type and other subtypes. AB - Adult T-cell leukemia-lymphoma (ATL), characterized by various clinicopathological features, is divided into four clinical subtypes, namely, acute, lymphoma, chronic and smoldering types, and the treatment strategy differs according to the clinical subtype. The designation cutaneous type ATL has been proposed to describe a peculiar subgroup of smoldering type ATL in which the skin is predominantly affected. However, diagnostic criteria and prognostic factors for cutaneous type ATL remain to be determined. Therefore, we performed a retrospective study to obtain a precise method for subtype classification and to clearly define cutaneous type ATL. A total of 87 ATL patients (acute, n = 31; lymphoma, n = 6; chronic, n = 24; smoldering, n = 26) were enrolled. The human T lymphotropic virus type I (HTLV-1) proviral load in peripheral blood and the serum soluble interleukin-2 receptor (sIL-2R) level were evaluated with respect to the clinical features of the different types of ATL. The HTLV-1 proviral load was significantly increased in the acute and chronic type and the serum sIL-2R level was increased in the acute and lymphoma type. The HTLV-1 proviral load was significantly lower in cutaneous than other smoldering types of ATL without skin lesions. The clinical findings of cutaneous type ATL were also different from other subtypes. These results indicate that, in combination, determination of the HTLV-1 proviral load and the serum sIL-2R level is useful for distinguishing among the different types of ATL, and strongly suggest that cutaneous type ATL is a distinct clinical entity. PMID- 26134469 TI - Plasmonic swings during the Fenton reaction: catalytic sensing of organics in water via fullerene-decorated gold nanoparticles. AB - Fullerene-decorated gold nanoparticles were used to catalyse the Fenton reaction and the electron transfer cycle of the catalyst shifts the gold surface plasmon resonance back and forth. The plasmonic swing frequency is in accord with the redox reaction rate and could be applied for detection of organics in water. PMID- 26134468 TI - Long-term stability, functional competence, and safety of microencapsulated specific pathogen-free neonatal porcine Sertoli cells: a potential product for cell transplant therapy. AB - BACKGROUND: Porcine Sertoli cells (pSCs) have been employed for cell therapy in pre-clinical studies for several chronic/immune diseases as they deliver molecules associated with trophic and anti-inflammatory effects. To be employed for human xenografts, pSCs products need to comply with safety and stability. To fulfill such requirements, we employed a microencapsulation technology to increase pre-transplant storage stability of specific pathogen-free pSCs (SPF pSCs) and evaluated the in vivo long-term viability and safety of grafts. METHODS: Specific pathogen free neonatal pigs underwent testis excision under sterility. pSCs were isolated, characterized by immunofluorescence (IF) and cytofluorimetric analysis (CA) and examined in terms of viability and function [namely, production of anti-mullerian hormone (AMH), inhibin B, and transforming growth factor beta-1 (TFGbeta-1)]. After microencapsulation in barium alginate microcapsules (Ba-MC), long-term SPF-pSCs (Ba-MCpSCs) viability and barium concentrations were evaluated at 1, 24 throughout 40 h to establish pre transplant storage conditions. RESULTS: The purity of isolated pSCs was about 95% with negligible contaminating cells. Cultured pSCs monolayers, both prior to and after microencapsulation, maintained high function and full viability up to 24 h of storage. At 40 h post-encapsulation, pSCs viability decreased to 80%. Barium concentration in Ba-MCpSCs lagged below the normal maximum daily allowance and was stable for 4 months in mice with no evident side effects. CONCLUSIONS: Such results suggest that this protocol for the isolation and microencapsulation of pSCs is compatible with long-haul transportation and that Ba-MCpSCs could be potentially employable for xenotransplantation. PMID- 26134471 TI - alpha-Linolenic Acid Reduces Growth of Both Triple Negative and Luminal Breast Cancer Cells in High and Low Estrogen Environments. AB - Flaxseed, rich in alpha-linolenic acid (ALA), is a complementary breast cancer (BC) therapy; however ALA effectiveness and mechanism are unclear. Variation in cellular expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and estrogen (E2) levels may alter ALA effectiveness. This research determined the effect of ALA on growth, apoptosis, and phospholipid fatty acids of 4 BC cell lines with varying receptor expression +/- E2. MCF-7 (ER+/PR+/HER2-), BT-474 (ER+/PR+/HER2+), MDA-MB-231 (ER-/PR-/HER2-) and MDA-MB-468 (ER-/PR-/HER2-) cells were incubated with ALA (50-200 MUM) +/- 1 nM E2 for 48-72 h. ALA dose-dependently reduced growth, measured by trypan blue exclusion, of all cells (55-80% with 75 MUM), and this effect was not altered by E2. ALA (75 MUM)+E2 induced apoptosis, measured by flow cytometry (up to 111.2%). Decreased growth and increased apoptosis is related to increased cell phospholipid % ALA (up to 25.1%), measured by gas chromatography. ALA is shown for the first time to reduce cell growth and induce apoptosis regardless of receptor expression and E2 environment, by incorporating into BC phospholipids, supporting the use of ALA and ALA-rich foods as a safe, inexpensive complementary therapy for a wide range of BC. PMID- 26134472 TI - Understanding the Growth Rates of Polymer Cocrystallization in the Binary Mixtures of Different Chain Lengths: Revisited. AB - Polymers often contain a polydispersity of chain lengths, which brings a complicated influence on crystallization behaviors. In our previous publication (J. Phys. Chem. B 2008, 112, 7370), we reported dynamic Monte Carlo simulations of cocrystallization in the binary mixtures of long (32-mer) and short (16-mer) homologue chains. We observed a linear dependence of crystal growth rates on the volume fractions of the long-chain component at low temperatures. In this article, with new confirming data, we further observed that the mole fractions also give linear dependence to the crystal growth rates, but split into two regimes. We attributed the phenomenon of two regimes to the variation between two thicknesses of lamellar crystals. The small thickness in the regime of low mole fractions is dominated by the metastable integer-number folding of 16-mers, which causes the "self-poisoning" effect on the crystal growth rates. PMID- 26134470 TI - Controlled Living Nanowire Growth: Precise Control over the Morphology and Optical Properties of AgAuAg Bimetallic Nanowires. AB - Inspired by the concept of living polymerization reaction, we are able to produce silver-gold-silver nanowires with a precise control over their total length and plasmonic properties by establishing a constant silver deposition rate on the tips of penta-twinned gold nanorods used as seed cores. Consequently, the length of the wires increases linearly in time. Starting with ~210 nm * 32 nm gold cores, we produce nanowire lengths up to several microns in a highly controlled manner, with a small self-limited increase in thickness of ~4 nm, corresponding to aspect ratios above 100, whereas the low polydispersity of the product allows us to detect up to nine distinguishable plasmonic resonances in a single colloidal solution. We analyze the spatial distribution and the nature of the plasmons by electron energy loss spectroscopy and obtain excellent agreement between measurements and electromagnetic simulations, clearly demonstrating that the presence of the gold core plays a marginal role, except for relatively short wires or high-energy modes. PMID- 26134473 TI - Potency of Both Human Th1 and NK Helper Cell Activation is Determined by IL-12p70 Producing PAMP-Matured DCs. AB - Besides T helper (Th) cells, natural killer (NK) cells have also been described to participate in the shaping of dendritic cell (DC)-mediated adaptive immune responses. At present, it remains unclear to what extent the induction of these NK helper cell immune mechanisms is coupled with Th responses and whether both helper immune responses are induced by the same DC upon specific pathogen recognition receptor (PRR) stimulation. In this study, we demonstrate that maturation of DCs with a cocktail containing FMKp (membrane fragments of Klebsiella pneumoniae) mounts both Th cell and NK cell helper responses in a PRR triggered dose-dependent manner as determined by the capacity of the helper cells to produce IFN-gamma. Furthermore, by triggering an additional PRR pathway [FMKp in combination with poly(I:C) lyovec], we reveal that both approaches modulate the amount of DC-derived IL-12p70 and that this cytokine is the key determinant of the DC-induced Th1 and NK cell helper responses. Moreover, all PRR triggers able to induce IL-12-producing mature DCs are sufficient to induce these helper responses. We propose the existence of a single program used by DCs to induce potent cellular immune responses by stimulating both T helper and NK cell helper processes. This knowledge can help to select the proper PRR triggers in preventive and therapeutic vaccine design. PMID- 26134476 TI - Hierarchical nanostructured WO3-SnO2 for selective sensing of volatile organic compounds. AB - It remains a challenge to find a suitable gas sensing material that shows a high response and shows selectivity towards various gases simultaneously. Here, we report a mixed metal oxide WO3-SnO2 nanostructured material synthesized in situ by a simple, single-step, one-pot hydrothermal method at 200 degrees C in 12 h, and demonstrate its superior sensing behavior towards volatile organic compounds (VOCs) such as ammonia, ethanol and acetone. SnO2 nanoparticles with controlled size and density were uniformly grown on WO3 nanoplates by varying the tin precursor. The density of the SnO2 nanoparticles on the WO3 nanoplates plays a crucial role in the VOC selectivity. The responses of the present mixed metal oxides are found to be much higher than the previously reported results based on single/mixed oxides and noble metal-doped oxides. In addition, the VOC selectivity is found to be highly temperature-dependent, with optimum performance obtained at 200 degrees C, 300 degrees C and 350 degrees C for ammonia, ethanol and acetone, respectively. The present results on the cost-effective noble metal-free WO3-SnO2 sensor could find potential application in human breath analysis by non-invasive detection. PMID- 26134475 TI - Pharmacology of Indole and Indazole Synthetic Cannabinoid Designer Drugs AB FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA. AB - Synthetic cannabinoid (SC) designer drugs based on indole and indazole scaffolds and featuring l-valinamide or l-tert-leucinamide side chains are encountered with increasing frequency by forensic researchers and law enforcement agencies and are associated with serious adverse health effects. However, many of these novel SCs are unprecedented in the scientific literature at the time of their discovery, and little is known of their pharmacology. Here, we report the synthesis and pharmacological characterization of AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, 5F-ADBICA, and several analogues. All synthesized SCs acted as high potency agonists of CB1 (EC50 = 0.24-21 nM) and CB2 (EC50 = 0.88-15 nM) receptors in a fluorometric assay of membrane potential, with 5F-ADB-PINACA showing the greatest potency at CB1 receptors. The cannabimimetic activities of AB-FUBINACA and AB-PINACA in vivo were evaluated in rats using biotelemetry. AB-FUBINACA and AB-PINACA dose-dependently induced hypothermia and bradycardia at doses of 0.3-3 mg/kg, and hypothermia was reversed by pretreatment with a CB1 (but not CB2) antagonist, indicating that these SCs are cannabimimetic in vivo, consistent with anecdotal reports of psychoactivity in humans. PMID- 26134477 TI - Blunt maxillary fracture and cheek bite: two rare causes of traumatic pneumomediastinum. AB - Subcutaneous facial emphysema is a well-known consequence of oral and maxillofacial traumatic injury. In some rare cases, the subcutaneous air collection could spread through the retropharyngeal and paralatero-cervical spaces, reaching the mediastinum. This clinical entity is known as pneumomediastinum and represents a severe and, sometimes, life-threatening condition. Other reported causes of pneumomediastinum are esophageal and tracheal traumatic or iatrogenic rupture. Finally, the so-called spontaneous pneumomediastinum is caused by a sudden increase in alveolar pressure and is usually seen in young men. We present two cases of pneumomediastinum as a consequence of unusual traumatic damage of orofacial tissues, followed by repeated sneezing and Valsalva maneuver. PMID- 26134478 TI - Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection. AB - INTRODUCTION: With the introduction of the coformulated dolutegravir, abacavir and lamivudine , a new single tablet regimen (STR) is made available for the use in treatment-naive and treatment-experienced HIV-infected patients. This drug combination is the fourth STR that will be positioned next to the STRs with efavirenz, rilpivirine or elvitegravir as third agents, respectively. AREAS COVERED: The objective of this review is to provide an overview of the efficacy and safety of the combined dolutegravir/abacavir/lamivudine coformulation. The review will focus on dolutegravir and includes both published data as well as data presented at recent major international HIV/AIDS conferences. EXPERT OPINION: The dolutegravir/abacavir/lamivudine regimen is highly effective in achieving sustained suppression of HIV-1 RNA plasma concentrations. The STR has a favorable safety profile and a low potential for drug interactions, which will contribute to a prominent role in therapy. As this STR contains abacavir as backbone component, the use requires patients to be HLA-B*5701 negative, with good hepatic function. Other first-line treatment combinations are preferred for patients with hepatitis B co-infection or with a high cardiovascular risk. PMID- 26134479 TI - Entrapment of a chiral cobalt complex within silver: a novel heterogeneous catalyst for asymmetric carboxylation of benzyl bromides with CO2. AB - A novel way to accommodate heterogeneous catalysis, CO2 fixation and asymmetric synthesis on one catalyst is reported. The [Co]@Ag composite was prepared for the first time and used for asymmetric carboxylation of benzyl bromides with CO2. All the procedures were performed under mild conditions. Moreover, the [Co]@Ag composite has terrific stability and reusability. PMID- 26134481 TI - The Patentability of Stem Cells in Australia. AB - The potential therapeutic applications of stem cells are unlimited. However, the ongoing political and social debate surrounding the intellectual property and patenting considerations of stem cell research has led to the implementation of strict legislative regulations. In Australia the patent landscape surrounding stem cells has evolved considerably over the past 20 years. The Australian Patents Act 1990 includes a specific exclusion to the patentability of human beings and of biological processes for their generation. However, this exclusion has received no judicial consideration to date, and so its scope and potential impact on stem cell patents is unclear. PMID- 26134482 TI - Interfacing Solution-Grown C60 and (3-Pyrrolinium)(CdCl3 ) Single Crystals for High-Mobility Transistor-Based Memory Devices. AB - Aligned ferroelectric single crystals of (3-pyrrolinium)(CdCl3 ) can be prepared from solution on top of aligned semiconducting C60 single crystals using an orthogonal solvent. Memory devices based on these ferroelectric/semiconductor bilayered heterojunctions exhibit much larger hysteresis compared with that of only C60 single crystals. More importantly, the introduction of the ferroelectric layer induces the memory window without dramatically reducing the charge mobility. PMID- 26134480 TI - Immune Response in Hepatitis B Virus Infection. AB - Hepatitis B virus (HBV) can replicate within hepatocytes without causing direct cell damage. The host immune response is, therefore, not only essential to control the spread of virus infection, but it is also responsible for the inflammatory events causing liver pathologies. In this review, we discuss how HBV deals with host immunity and how we can harness it to achieve virus control and suppress liver damage. PMID- 26134483 TI - Pott's Disease of the Thoracic Spine and Abscess of the Chest Wall. PMID- 26134485 TI - Site Selective Azo Coupling for Peptide Cyclization and Affinity Labeling of an SH3 Protein. AB - A key challenge in bioconjugation is to control the site selectivity of the reaction. Chemical reagents often react with proteineous chemical groups without showing preference to their location or microenvironment in the protein; to confine the reaction to an amino acid at a specific site, one needs to distinguish this residue from others despite their identical chemical properties. Here, we report a strategy that utilizes proximity-driven reactivity to achieve site selective azo coupling between tyrosine and aryldiazonium. A phenylalanine analogue with an aryldiazonium moiety at its side chain was incorporated into a synthetic peptide and was found to react only with tyrosine in its vicinity but also to remain inert to others that are not immediately adjacent, a property attained by fine regulation of the electronic effect of the substituent on the aryl ring. Proximity-driven intramolecular azo coupling was showcased in cyclization of a beta-hairpin peptide, structural features of the azo linked cyclic peptide was elucidated by NMR, and intermolecular azo coupling was achieved between an SH3 protein Abl-SH3 and its polyproline peptide ligands at specific tyrosine residues. This approach is generally applicable to develop covalent affinity labels for SH3 proteins because of the high occurrence rate of tyrosine at the peptide-binding site of SH3 proteins. PMID- 26134486 TI - Confocal microscopy characterization of BRAFV600E mutated melanomas. AB - Thanks to modern techniques, molecular signatures for melanoma are now identifiable and have opened new horizons in the treatment of metastatic disease with molecular-targeted therapies. We distinguish different melanoma subtypes on the basis of genetic mutations such as BRAFV600E and we can therefore hypothesize the existence of corresponding morphological patterns that might be detected in vivo by noninvasive diagnostic tools such as dermoscopy and confocal microscopy. Eight BRAFV600E mutated melanomas (six primary and two metastases) were collected, matched in terms of age, sex, and thickness wild-type controls, and analyzed. In this preliminary study, regression, corresponding to fibrosis and melanophages in the dermis, was the predominant pattern and was also observed confocally when dermoscopy showed no peppering. In particular, confocal microscopy could not only detect regression but also provided a semiquantitative analysis of its grade through the count of melanophages. Confocal microscopy can be proposed as a useful tool in the preliminary screening and characterization of BRAFV600E mutated melanomas, providing new insights for patients' screening and follow-up. PMID- 26134484 TI - Differential Effects of Glycyrrhiza Species on Genotoxic Estrogen Metabolism: Licochalcone A Downregulates P450 1B1, whereas Isoliquiritigenin Stimulates It. AB - Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by upregulating P450 1B1. The present study tested the three authenticated medicinal species of licorice [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)] used by women as dietary supplements for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI-specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI ? GG > GU and LigC ? LicA ? LigF. The Michael acceptor chalcone, LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as nontoxic and 4-MeOE1 as genotoxic biomarkers in the nontumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 MUg/mL), and LigC (1 MUM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-alpha and IFN-gamma). LicA (1, 10 MUM) decreased cytokine- and TCDD-induced P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50 = 12.3 MUM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 MUg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that, of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women's health. Additionally, the differential effects of the Glycyrrhiza species on estrogen metabolism emphasize the importance of standardization of botanical supplements to species-specific bioactive compounds. PMID- 26134487 TI - A new steroid from the Red Sea soft coral Lobophytum lobophytum. AB - Chemical investigation of the soft coral Lobophytum lobophytum collected from the Red Sea led to the isolation of a new compound gorgostan-5,25-dien-3beta-ol (1), and two known compounds gorgosterol (2), and alismol (3). Structures were elucidated by employing extensive NMR and HR-ESI-MS experiments. PMID- 26134488 TI - Needs assessment to improve neonatal intensive care in Mexico. AB - BACKGROUND: At the time of the research, Dr Weiss was a clinical fellow in neonatal-perinatal medicine at Baylor College of Medicine, Texas Children's Hospital. Dr Profit was on faculty at Baylor College of Medicine, Texas Children's Hospital, Department of Pediatrics, Section of Neonatology. He held a secondary appointment in the Department of Medicine, Section of Health Services Research and conducted his research at the VA Health Services Research and Development Center of Excellence where he collaborated with Dr Kowalkowski.: Improving the quality of neonatal intensive care is an important health policy priority in Mexico. A formal assessment of barriers and priorities for quality improvement has not been undertaken. AIM: To provide guidance to providers and policy makers with regard to addressing opportunities for better care delivery in Mexican neonatal intensive care units. OBJECTIVE: To conduct a needs assessment regarding improvement of quality of neonatal intensive care delivery in Mexico. METHODS: Spanish-language survey administered to a volunteer sample of Mexican neonatal care providers attending a large paediatric conference in Mexico in June 2011. Survey domains included institutional context of quality improvement, barriers, priorities, safety culture, and respondents' characteristics. Results were analysed using descriptive analyses of frequencies, proportions and percentage positive response (PPR) rates. RESULTS: Of 91 respondents, the majority identified neonatology as their primary specialty (n = 48, 65%) and were physicians (n = 55, 73%). Generally, providers expressed a desire to improve quality of care (PPR 69%) but reported notable deterrents. Respondents (n, %) identified family inability to pay (38, 48%), overcrowded work areas (38, 44%), insufficient financial reimbursement (25, 36%), lack of availability of nurses (26, 30%), ancillary staff (25, 29%), and subspecialists (22, 25%) as the principal barriers. Respiratory care (27, 39%)--reduction of mechanical ventilation and initiation of nasal continuous positive airway pressure--and reduction in frequency of late-onset infections (19, 28%) were selected as top clinical priorities. There were substantial opportunities for improving safety (PPR 48%) and teamwork climate (PPR 58%). CONCLUSION: These findings may guide efforts to improving quality of care delivery in Mexican neonatal intensive care units. PMID- 26134489 TI - An Experimental Study of Medical Error Explanations: Do Apology, Empathy, Corrective Action, and Compensation Alter Intentions and Attitudes? AB - Medical malpractice lawsuits are a growing problem in the United States, and there is much controversy regarding how to best address this problem. The medical error disclosure framework suggests that apologizing, expressing empathy, engaging in corrective action, and offering compensation after a medical error may improve the provider-patient relationship and ultimately help reduce the number of medical malpractice lawsuits patients bring to medical providers. This study provides an experimental examination of the medical error disclosure framework and its effect on amount of money requested in a lawsuit, negative intentions, attitudes, and anger toward the provider after a medical error. Results suggest empathy may play a large role in providing positive outcomes after a medical error. PMID- 26134490 TI - Influence of intramammary infection of a single gland in dairy cows on the cow's milk quality. AB - Intramammary infection (IMI), comprises a group of costly diseases affecting dairy animals worldwide. Many dairy parlours are equipped with on-line computerised data acquisition systems designed to detect IMI. However, the data collected is related to the cow level, therefore the contribution of infected glands to the recorded parameters may be over estimated. The present study aimed at evaluating the influence of single gland IMI by different bacteria species on the cow's overall milk quality. A total of 130 cows were tested 239 times; 79 cows were tested once and the others were examined 2-8 times. All of the analysed data refer to the number of tests performed, taking into account the repeated testing of the same cows. Of the cows tested ~50% were free of infection in all 4 glands and the others were infected in one gland with different coagulase negative staphylococci (CNS), Streptococcus dysgalactiae, or were post infected with Escherichia coli (PIEc), i.e., free of bacterial infection at the time of sampling but 1-2 months after clinical infection by E. coli. Overall, infection with bacteria had significant effects on somatic cell count (SCC) and lactose concentration. Examining each bacterium reveals that the major influence on those parameters was the sharp decrease in lactose in the PIEc and curd firmness in PIEc and Strep. Individual gland milk production decreased ~20% in Strep. dysgalactiae- and ~50% in PIEc-infected glands with respect to glands with no bacterial findings. Significant differences were found in lactose, SCC, rennet clotting time and curd firmness in the milk of infected glands and among those, these parameters were significantly higher in Strep. dysgalactiae and PIEc than in CNS infected cows. The current results using quarter-milking reinforces the importance of accurate IMI detection in relation to economic and welfare factors, and moreover, emphasises the need for technical sensing and constant reporting to the farmer about changes in the milk quality of every animal. PMID- 26134491 TI - miR-133a inhibits cervical cancer growth by targeting EGFR. AB - MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in cervical carcinogenesis and progression. microRNA-133a (miR-133a) has been reported to play a tumor-suppressor role in a range of cancers. However, the role and underlying molecular mechanism of miR-133a in cervical cancer have not been investigated. In the present study, we investigated the role of miR-133a in the tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-133a was investigated using real-time reverse transcription-polymerase chain reaction (qRT-PCR) in 30 cervical specimens and matched adjacent normal tissues and cervical cancer cell lines. We found that the expression level of miR-133a was significantly downregulated in cervical cancer tissues and cervical cancer cell lines, and the aberrant expression of miR-133a was correlated with lymph node metastasis, histological grade and FIGO stage. The role of miR-133a in tumorigenicity of cervical cancer cells was assessed by the restoration of miR 133a. We found that restoration of miR-133a inhibited cell proliferation, colony formation, migration and invasion, promoted cell apoptosis in vitro and suppressed tumorigenicity in vivo. The epidermal growth factor receptor (EGFR) was confirmed to be a direct target of miR-133a in cervical cancer cells using luciferase assay and western blotting. Restoration of miR-133a inhibited EGFR expression and activated the AKT and ERK signaling pathways. These results showed that miR-133a suppresses cervical cancer growth in vitro and in vivo through targeting EGFR, suggesting that miR-133a can be a potential target for the treatment of cervical cancer. PMID- 26134492 TI - Intraoperative Measurement of the Distance from the Bottom of Osteotomy to the Mandibular Canal Using a Novel Ultrasonic Device. AB - BACKGROUND: In our previous study, we found that a novel ultrasound (US) device may serve as a useful intraoperative tool to measure the distance from osteotomy to the inferior alveolar canal (IAC). PURPOSE: To validate our previous results in a larger group of osteotomies in the posterior mandible. METHODS: During dental implant placement surgery, osteotomies were created using a standardized 2 mm-diameter pilot drill. The distance from the bottom of the osteotome to the IAC was assessed using an ultrasonic device and compared with a standard panoramic radiograph used to measure the same residual distance. The total distance from the crestal bone to the IAC was measured on a preoperative computed tomography (CT) and compared with total US measurements by summing the drill depth with residual depth measurements. RESULTS: Mean radiographic and US residual distances were 5.19 +/- 1.95 mm, 5.01 +/- 1.82 mm, p = 0.79 respectively. These measurements presented strong positive correlations (r = 0.61, p = .01). Mean total CT distance was 13.48 +/- 2.66 mm; mean total US calculation was 13.69 +/- 2.51 mm. No significant difference was found (p > .05). CONCLUSIONS: The results support our previous pilot study and confirm that the tested US device identifies the IAC and measures the distance from the osteotomy to the roof of the mandibular canal. PMID- 26134493 TI - Giving Your Last Gift: A Study of the Knowledge, Attitude and Information of Greek Students Regarding Organ Donation. AB - BACKGROUND: Organ donation rates in Greece are the lowest in the European Union. Studying and improving young students' awareness may increase organ donation rates. This study aimed to investigate young students' knowledge, attitude and information regarding organ donation and whether they are modified by putative predictors. MATERIAL AND METHODS: A 62-item electronic questionnaire was sent to 1451 eligible students aged 18-30 years in 16 Greek public technical schools. Two composite scales (knowledge and attitude) were created. The multivariate statistical analysis included ordinal logistic and linear regression, as appropriate. RESULTS: Only 37.9% of the students knew the correct definition of organ donation, 40.3% knew which organs can be donated, 27.4% were informed about the new Greek legislation, and 83.1% acknowledged the need for better information. Although 60.5% would donate an organ after death, only 16.1% would become living donors. Although 83.1% of the students declared knowing what brain death means, 18.6% believe that a brain-dead person could fully recover and 32.3% are unsure about it. Being a health professional or a blood donor, the parent's educational level, the wish to donate all organs after death, the information from announcements or posters, the fear of organ removal after death without prior consent, the consent for autopsy, the wish for better information, and the misbelief that a brain-dead person could fully recover emerged as important predictors of the knowledge and attitude, regarding organ donation. CONCLUSIONS: An important lack of knowledge and misperceptions were noted regarding organ donation. Significant predictors were identified. PMID- 26134494 TI - Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor. AB - Comprehensive studies that consolidate selective ligands, quantitative comparisons of G protein versus arrestin-2/3 coupling, together with structure activity relationship models for G protein-coupled receptor (GPCR) systems are less commonly employed. Here we examine biased signaling at the nociceptin/orphanin FQ opioid receptor (NOPR), the most recently identified member of the opioid receptor family. Using real-time, live-cell assays, we identified the signaling profiles of several NOPR-selective ligands in upstream GPCR signaling (G protein and arrestin pathways) to determine their relative transduction coefficients and signaling bias. Complementing this analysis, we designed novel ligands on the basis of NOPR antagonist J-113,397 [(+/-)-1 [(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3 dihydro-2H-benzimidazol-2-one] to explore structure-activity relationships. Our study shows that NOPR is capable of biased signaling, and further, the NOPR selective ligands MCOPPB [1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-(3R)-3 piperidinyl-1H-benzimidazole trihydrochloride] and NNC 63-0532 [8-(1 naphthalenylmethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-3-acetic acid, methyl ester] are G protein-biased agonists. Additionally, minor structural modification of J-113,397 can dramatically shift signaling from antagonist to partial agonist activity. We explore these findings with in silico modeling of binding poses. This work is the first to demonstrate functional selectivity and identification of biased ligands at the nociceptin opioid receptor. PMID- 26134496 TI - How Well Do Molecular and Pedigree Relatedness Correspond, in Populations with Diverse Mating Systems, and Various Types and Quantities of Molecular and Demographic Data? AB - Kinship analyses are important pillars of ecological and conservation genetic studies with potentially far-reaching implications. There is a need for power analyses that address a range of possible relationships. Nevertheless, such analyses are rarely applied, and studies that use genetic-data-based-kinship inference often ignore the influence of intrinsic population characteristics. We investigated 11 questions regarding the correct classification rate of dyads to relatedness categories (relatedness category assignments; RCA) using an individual-based model with realistic life history parameters. We investigated the effects of the number of genetic markers; marker type (microsatellite, single nucleotide polymorphism SNP, or both); minor allele frequency; typing error; mating system; and the number of overlapping generations under different demographic conditions. We found that (i) an increasing number of genetic markers increased the correct classification rate of the RCA so that up to >80% first cousins can be correctly assigned; (ii) the minimum number of genetic markers required for assignments with 80 and 95% correct classifications differed between relatedness categories, mating systems, and the number of overlapping generations; (iii) the correct classification rate was improved by adding additional relatedness categories and age and mitochondrial DNA data; and (iv) a combination of microsatellite and single-nucleotide polymorphism data increased the correct classification rate if <800 SNP loci were available. This study shows how intrinsic population characteristics, such as mating system and the number of overlapping generations, life history traits, and genetic marker characteristics, can influence the correct classification rate of an RCA study. Therefore, species specific power analyses are essential for empirical studies. PMID- 26134497 TI - The phosphorylation of alpha-synuclein: development and implication for the mechanism and therapy of the Parkinson's disease. AB - Parkinson's disease (PD) is cited to be the second most common neuronal degenerative disorders; however, the exact mechanism of PD is still unclear. alpha-synuclein is one of the key proteins in PD pathogenesis as it's the main component of the PD hallmark Lewy bodies (LBs). Nowadays, the study of alpha synuclein phosphorylation mechanism related to the PD pathology has become a research hotspot, given that 90% of alpha-synuclein deposition in LBs is phosphorylated at Ser129, whereas in normal brains, only 4% or less of alpha synuclein is phosphorylated at the residue. Here, we review the related study of PD pathological mechanism involving the phosphorylation of alpha-synuclein mainly at Ser129, Ser87, and Tyr125 residues in recent years, as well as some explorations relating to potential clinical application, in an attempt to describe the development and implication for the mechanism and therapy of PD. Given that some of the studies have yielded paradoxical results, there is need for more comprehensive research in the field. The phosphorylation of alpha synuclein might provide a breakthrough for PD mechanism study and even supply a new therapeutic strategy. The milestone study on the phosphorylation of alpha synuclein mainly at Ser129, Ser87, and Tyr125 relating to PD in recent years as well as some clinical application exploration are overviewed. The potential pathways of the phosphorylated alpha-synuclein related to PD are also summarized. The review may supply more ideas and thinking on this issue for the scientists in related research field. PMID- 26134495 TI - Fulfilling the Promise of "Biased" G Protein-Coupled Receptor Agonism. AB - The fact that over 30% of current pharmaceuticals target heptahelical G protein coupled receptors (GPCRs) attests to their tractability as drug targets. Although GPCR drug development has traditionally focused on conventional agonists and antagonists, the growing appreciation that GPCRs mediate physiologically relevant effects via both G protein and non-G protein effectors has prompted the search for ligands that can "bias" downstream signaling in favor of one or the other process. Biased ligands are novel entities with distinct signaling profiles dictated by ligand structure, and the potential prospect of biased ligands as better drugs has been pleonastically proclaimed. Indeed, preclinical proof-of concept studies have demonstrated that both G protein and arrestin pathway selective ligands can promote beneficial effects in vivo while simultaneously antagonizing deleterious ones. But along with opportunity comes added complexity and new challenges for drug discovery. If ligands can be biased, then ligand classification becomes assay dependent, and more nuanced screening approaches are needed to capture ligand efficacy across several dimensions of signaling. Moreover, because the signaling repertoire of biased ligands differs from that of the native agonist, unpredicted responses may arise in vivo as these unbalanced signals propagate. For any given GPCR target, establishing a framework relating in vitro efficacy to in vivo biologic response is crucial to biased drug discovery. This review discusses approaches to describing ligand efficacy in vitro, translating ligand bias into biologic response, and developing a systems level understanding of biased agonism in vivo, with the overall goal of overcoming current barriers to developing biased GPCR therapeutics. PMID- 26134498 TI - Erratum to: Antitumor activity of the ERK inhibitor SCH722984 against BRAF mutant, NRAS mutant and wild-type melanoma. PMID- 26134499 TI - Erratum to GLP-1 receptor agonists: a review of head-to-head clinical studies. AB - SAGE Publications wish to apologise for the following error which was introduced into "GLP-1 receptor agonists: a review of head-to-head clinical studies" by Jennifer M. Trujillo, Wesley Nuffer and Samuel L. Ellis. This article was published in Therapeutic Advances in Endocrinology and Metabolism 2015, volume 6(1) 19-28, DOI: 10.1177/2042018814559725. PMID- 26134500 TI - Prognostic significance of ALCAM (CD166/MEMD) expression in cutaneous melanoma patients. AB - BACKGROUND: ALCAM (activated leukocyte cell adhesion molecule, CD166, MEMD) is a transmembrane protein of immunoglobulin superfamily (Ig-SF) and plays an important role in human malignant melanoma progression and formation of locoregional and distant metastases. The study using melanoma cell lines showed that overexpression of ALCAM is directly related with the increase of cytoaggregation and the ability to form cell nests. The aim of the study was to assess the expression and intracellular localization of ALCAM in primary skin melanomas and metastatic lesions from regional lymph nodes. Also, prognostic significance of ALCAM expression in primary tumor cells and metastatic lesion cells was evaluated in the context of 5-year observation. METHODS: Formalin-fixed paraffin-embedded tissue specimens from 104 primary cutaneous melanomas and 16 regional lymph nodes metastases were studied for the expression of ALCAM measured by immunohistochemistry. RESULTS: We demonstrate that high ALCAM expression in primary melanoma cells (IRS >=8) is strongly correlated with unfavorable prognosis as compared with patients with lower ALCAM immunoreactivity in tumor compartment as regards cancer specific overall survival (CSOS) (P = 0.001) and disease free survival (DFS) (P < 0.001). Additionally lower ALCAM immunoreactivity in nodal metastatic foci was significantly statistically correlated with deeper melanoma invasion in the primary tumor according to Clark scale (P = 0.032). It was also found that decreased ALCAM expression (IRS <8) in nodal metastases shows a trend related with a correlation with shorter cancer specific overall survival (P = 0.083). Statistically significant correlations were also demonstrated between the presence of ulceration and decreased intensity of lymphocytic inflammatory infiltration and a high percentage of ALCAM-positive cells (P = 0.035, P = 0.01, respectively). CONCLUSIONS: High ALCAM expression in melanoma cells of the primary tumor can be used as a marker of negative outcome and may indicate a more invasive phenotype of cancer cells, which would require a more intensive therapeutic strategy. Low expression of ALCAM in regional lymph node metastases is a feature associated with unfavorable prognosis in patients with cutaneous melanoma. Our study is the first one to evaluate the effect of increased ALCAM expression on long-term survival in melanoma patients. PMID- 26134502 TI - Tannic acid modulates excitability of sensory neurons and nociceptive behavior and the Ionic mechanism. AB - M/Kv7 K(+) channels, Ca(2+)-activated Cl(-) channels (CaCCs) and voltage gated Na(+) channels expressed in dorsal root ganglia (DRG) play an important role in nociception. Tannic acid has been proposed to be involved in multiple beneficial health effects; tannic acid has also been described to be analgesic. However the underlying mechanism is unknown. In this study, we investigated the effects of tannic acid on M/Kv7 K(+), Na(+) currents and CaCCs, and the effects on bradykinin-induced nociceptive behavior. A perforated patch technique was used. The bradykinin-induced rat pain model was used to assess the analgesic effect of tannic acid. We demonstrated that tannic acid enhanced M/Kv7 K(+) currents but inhibited bradykinin-induced activation of CaCC/TMEM16A currents in rat small DRG neurons. Tannic acid potentiated Kv7.2/7.3 and Kv7.2 currents expressed in HEK293B cells, with an EC50 of 7.38 and 5.40 uM, respectively. Tannic acid inhibited TTX-sensitive and TTX-insensitive currents of small DRG neurons with IC50 of 5.25 and 8.43 uM, respectively. Tannic acid also potently suppressed the excitability of small DRG neurons. Furthermore, tannic acid greatly reduced bradykinin-induced pain behavior of rats. This study thus demonstrates that tannic acid is an activator of M/Kv7 K(+) and an inhibitor of voltage-gated Na(+) channels and CaCC/TMEM16A, which may underlie its inhibitory effects on excitability of DRG neurons and its analgesic effect. Tannic acid could be a useful agent in treatment of inflammatory pain conditions such as osteoarthritis, rheumatic arthritis and burn pain. PMID- 26134501 TI - Directed evolution of anti-HER2 DARPins by SNAP display reveals stability/function trade-offs in the selection process. AB - In vitro display technologies have proved to be powerful tools for obtaining high affinity protein binders. We recently described SNAP display, an entirely in vitro DNA display system that uses the SNAP-tag to link protein with its encoding DNA in water-in-oil emulsions. Here, we apply SNAP display for the affinity maturation of a designed ankyrin repeat proteins (DARPin) that binds to the extracellular domain of HER2 previously isolated by ribosome display. After four SNAP display selection cycles, proteins that bound specifically to HER2 in vitro, with dissociation constants in the low- to sub-nanomolar range, were isolated. In vitro affinities of the panel of evolved DARPins directly correlated with the fluorescence intensities of evolved DARPins bound to HER2 on a breast cancer cell line. A stability trade-off is observed as the most improved DARPins have decreased thermostability, when compared with the parent DARPin used as a starting point for affinity maturation. Dissection of the framework mutations of the highest affinity variant, DARPin F1, shows that functionally destabilising and compensatory mutations accumulated throughout the four rounds of evolution. PMID- 26134503 TI - Selenate specifically sensitizes drug-resistant cancer cells by increasing apoptosis via G2 phase cell cycle arrest without P-GP inhibition. AB - The purpose of this study was to identify conditions that will increase the sensitivity of drug-resistant cancer cells. Selenium derivatives have been shown to present anti-cancer properties in the clinic. Currently, selenate, selenite, selenomethionine (SeMet), methyl-selenocysteine (MSC), and methaneselenic acid (MSA) are the most common selenium derivatives used as drugs in humans. Herein, we tested whether these selenium derivatives can sensitize KBV20C cancer cells, which are highly resistant to anti-cancer drugs such as vincristine. All five drugs could sensitize KBV20C cells to the same extent as they sensitized the sensitive parent KB cells, suggesting that selenium-derived drugs can be used for drug-resistant cancer cells. We also observed that these drugs did not inhibit the P-glycoprotein (P-gp) pumping-out ability, suggesting that the sensitization by selenium-derived drugs does not depend on P-gp activity in resistant KBV20C cells. Interestingly, using a cell viability assay, microscopic observation, and Hoechst staining, we found that selenate highly sensitized drug-resistant KBV20C cells by activating the apoptotic pathway, when compared to sensitive KB cells. Furthermore, we investigated why selenate sensitizes resistant KBV20C cells. Selenate-induced toxicity was associated with an increase in G2-phase cell cycle arrest in KBV20C cells, suggesting that the selenate-induced increase in apoptosis resulted from cell cycle arrest in resistant KBV20C cells. Our findings may contribute to the development of selenate-based therapies for patients resistant to cancer drugs. PMID- 26134504 TI - Eucalyptol induces hyperexcitability and epileptiform activity in snail neurons by inhibiting potassium channels. AB - The effects of eucalyptol (1,8-cineole) were studied on the activity of central neurons of land snail Caucasotachea atrolabiata. Eucalyptol (3 mM) depolarized the membrane potential and increased the frequency of spontaneous activity in a time dependent and reversible manner. These effects were associated with suppression of afterhyperpolarization and significant reduction of amplitude and slope of rising and falling phases of action potentials. While the eucalyptol induced suppression of action potential amplitude and rising slope were essentially dependent on membrane depolarization, its actions on repolarization slope and afterhyperpolarization were not affected by resetting the membrane potential close to the control value. These findings suggest an inhibitory action on the potassium channels that underlie repolarization and afterhyperpolarization. Eucalyptol also increased the frequency of driven action potentials but suppressed the post stimulus inhibitory period, indicating an inhibitory action on calcium-activated potassium channels. A higher concentration of eucalyptol, 5mM, reversibly changed the pattern of activity to burst firing associated with paroxysmal depolarization shift (PDS). Low doses of eucalyptol and potassium channel blockers, tetraethylammonium and 4-aminopyridine, synergistically acted to induce burst firing. At high concentration (30 mM), tetraethylammonium was able to induce burst firing and PDS. The sodium currents and ion channel phosphorylation by protein kinases A and C were not required for the eucalyptol-induced epileptiform activity, but calcium currents were essential for this action. Our findings show the excitatory and epileptogenic action of eucalyptol, which is most likely mediated through direct inhibitory action on potassium channels. PMID- 26134505 TI - Hyper-osmolarity and calcium chelation: Effects on cystic fibrosis mucus. AB - A non-functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) leads to the disease cystic fibrosis (CF). Although the CFTR is expressed in multiple organs, pulmonary disease is the major cause of illness and death in patients with CF. Stagnant mucus, causing airway obstruction, bacterial overgrowth, persistent inflammation and tissue destruction characterizes the disease, but how the defect in CFTR function is coupled to the mucus phenotype is still controversial. We have recently shown that bicarbonate ions passing through CFTR are necessary for proper unfolding of the MUC2 mucin, thus highlighting the importance of bicarbonate ion transport via the CFTR and the ability of these ions to raise the pH and chelate calcium bound to the mucin as the important steps in forming normal mucus. In order to find potential CF treatments and expand our knowledge about the usefulness of bicarbonate as an active ingredient in formulations to alleviate mucus plugging, we used an Ussing-type chamber and explants from the F508del-CFTR mutant mouse ileum to test the effect of calcium chelators on mucus attachment, either in isolation or in combination with osmolytes such as mannitol or hypertonic saline. We found that increasing the concentration of bicarbonate, both alone or in combination with increased osmolarity of the solution, detached the otherwise attached CF mucus. PMID- 26134506 TI - Chansu inhibits the expression of cortactin in colon cancer cell lines in vitro and in vivo. AB - BACKGROUND: Chansu is a transitional Chinese medicine that has been used for centuries as therapy for inflammation, anaesthesia and arrhythmia in China and other Asian countries. Recently, it has also been used for anti-cancer purposes. We have previously shown that Chansu has a huge pro-apoptotic potential on colon cancer cells, but to date the detailed mechanism of this action is not well understood. METHODS: One of the major components of Chansu, Cinobufagin (CBF) was used to treat cancer cells. The expressions of levels of cortactin, an important factor in tumour progression and cancer invasion, were assessed in in vitro and in vivo experiments. Additional analyses were performed in subcellular protein fractions and immune-fluorescent staining was used to define cortactin protein expression and the changes of location in CBF-treated cells. RESULTS: CBF strongly inhibited the expression of cortactin in HCT116 cells. There were reductions of both mRNA transcription and protein synthesis, which were more significant in the absence of oxygen in vitro. In addition, nuclear translocation of cortactin was observed in HCT116 cells post CBF exposure but not in the negative control, indicating that CBF is likely to interrupt co-localisation of cortactin to cytoskeletal proteins. Most importantly, CBF could diminish the expression of cortactin in human HCT116 xenograft tumours in nude mouse in vivo. CONCLUSIONS: CBF inhibits cortactin expression and nuclear translocation in colon cancer cells in vitro and in mouse models bearing human colon tumour in vivo, suggesting it might disrupt actin-regulated cell movement. Thus, CBF or Chansu could be developed as an effective anti-cancer therapy to stop local invasion and metastasis. PMID- 26134507 TI - Prevalence of allergic conjunctivitis among basic school children in the Kumasi Metropolis (Ghana): a community-based cross-sectional study. AB - BACKGROUND: There seems a preponderance of hospital-based studies on the prevalence of Allergic Conjunctivitis (AC) compared to community-based ones, particularly among children in Ghana and Africa as a whole. Meanwhile, literature supports the possibility of underdiagnosing AC in the hospital setting; exponentially so when males generally have poor hospital-attending behavior. This may lead to underestimation of the true burden of AC. Consequently, the purpose of the current community-based study was to determine the prevalence of AC among basic school children in the Kumasi Metropolis, while identifying its associated symptoms. METHODS: A cross-sectional community-based study involving 1571 students from 11 basic schools (Primary and JHS) participated in the study. Data collection started in November 2011 and was completed in March 2014. After history taking, subjects underwent a battery of tests; visual acuity, objective refraction, anterior and posterior segments examination with a slit-lamp and a direct ophthalmoscope respectively. RESULTS: The prevalence of AC was 39.9 %. The mean (+/- SD) age of participants was 8 +/- 0.65 years. AC was significantly associated with gender (p < 0.05), but not with age (p > 0.05). A total of 70 % of the students with AC never had any form of treatment. CONCLUSIONS: AC is an endemic ocular disease among basic schools in the Kumasi metropolis and therefore calls for pragmatic and proactive measures to reduce its burden and effects on its victims. Public health measures may be required to help reduce the burden associated with this condition. PMID- 26134509 TI - Wavelength-selective absorptance in GaAs, InP and InAs nanowire arrays. AB - The absorptance in vertical nanowire (nw) arrays is a result of three optical phenomena: radial mode resonances, near-field evanescent wave coupling, and Fabry Perot (F-P) modes. The contribution of these optical phenomena to GaAs, InP and InAs nw absorptance was simulated using the finite element method. The study compared the absorptance between finite and semi-infinite nw lengths with varying geometrical parameters, including the nw diameter, length and array period. Simulation results showed that the resonance peak wavelength of the HE11 and HE12 radial modes linearly red-shifted with increasing nw diameter. The absorptance and spectral width of the resonance peaks increased as the nw length increased, with an absorptance plateau for very long nws that depended on diameter and period. Near-field coupling between neighboring nws was observed to increase with decreasing period. The effect of F-P modes was more pronounced for shorter nws, with a significant enhancement of HE12 over HE11 absorptance. Engineering of nw arrays to take advantage of these optical phenomena for multi-spectral photodetector applications is discussed. PMID- 26134508 TI - Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells. AB - Synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oate (CDDO-Me) has been shown as a promising agent against ovarian cancer. However, the underlying mechanism is not well understood. Here, we demonstrate that CDDO Me directly interacts with Hsp90 in cells by cellular thermal shift assay. CDDO Me treatment leads to upregulation of Hsp70 and degradation of Hsp90 clients (ErbB2 and Akt), indicating the inhibition of Hsp90 by CDDO-Me in cells. Knockdown of Hsp90 significantly inhibits cell proliferation and enhances the anti-proliferation effect of CDDO-Me in H08910 ovarian cancer cells. Dithiothreitol inhibits the interaction of CDDO-Me with Hsp90 in cells and abrogates CDDO-Me induced upregulation of Hsp70, degradation of Akt and cell proliferation inhibition. This suggests the anti-ovarian cancer effect of CDDO-Me is possibly mediated by the formation of Michael adducts between CDDO-Me and reactive nucleophiles on Hsp90. This study identifies Hsp90 as a novel target protein of CDDO-Me, and provides a novel insight into the mechanism of action of CDDO-Me in ovarian cancer cells. PMID- 26134510 TI - Huaier Extract Induces Autophagic Cell Death by Inhibiting the mTOR/S6K Pathway in Breast Cancer Cells. AB - Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects. Here, we investigated the role of autophagy in Huaier-induced cytotoxicity in MDA MB-231, MDA-MB-468 and MCF7 breast cancer cells. Huaier treatment inhibited cell viability in all three cell lines and induced various large membranous vacuoles in the cytoplasm. In addition, electron microscopy, MDC staining, accumulated expression of autophagy markers and flow cytometry revealed that Huaier extract triggered autophagy. Inhibition of autophagy attenuated Huaier-induced cell death. Furthermore, Huaier extract inhibited the mammalian target of the rapamycin (mTOR)/S6K pathway in breast cancer cells. After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth. This study is the first to show that Huaier-induced cytotoxicity is partially mediated through autophagic cell death in breast cancer cells through suppression of the mTOR/S6K pathway. PMID- 26134511 TI - VirtualDose: a software for reporting organ doses from CT for adult and pediatric patients. AB - This paper describes the development and testing of VirtualDose--a software for reporting organ doses for adult and pediatric patients who undergo x-ray computed tomography (CT) examinations. The software is based on a comprehensive database of organ doses derived from Monte Carlo (MC) simulations involving a library of 25 anatomically realistic phantoms that represent patients of different ages, body sizes, body masses, and pregnant stages. Models of GE Lightspeed Pro 16 and Siemens SOMATOM Sensation 16 scanners were carefully validated for use in MC dose calculations. The software framework is designed with the 'software as a service (SaaS)' delivery concept under which multiple clients can access the web-based interface simultaneously from any computer without having to install software locally. The RESTful web service API also allows a third-party picture archiving and communication system software package to seamlessly integrate with VirtualDose's functions. Software testing showed that VirtualDose was compatible with numerous operating systems including Windows, Linux, Apple OS X, and mobile and portable devices. The organ doses from VirtualDose were compared against those reported by CT-Expo and ImPACT-two dosimetry tools that were based on the stylized pediatric and adult patient models that were known to be anatomically simple. The organ doses reported by VirtualDose differed from those reported by CT-Expo and ImPACT by as much as 300% in some of the patient models. These results confirm the conclusion from past studies that differences in anatomical realism offered by stylized and voxel phantoms have caused significant discrepancies in CT dose estimations. PMID- 26134513 TI - A commentary on fine mapping and resequencing of the PARK16 locus in Parkinson's disease. PMID- 26134512 TI - Genetic mutations in human rectal cancers detected by targeted sequencing. AB - Colorectal cancer (CRC) is widespread with significant mortality. Both inherited and sporadic mutations in various signaling pathways influence the development and progression of the cancer. Identifying genetic mutations in CRC is important for optimal patient treatment and many approaches currently exist to uncover these mutations, including next-generation sequencing (NGS) and commercially available kits. In the present study, we used a semiconductor-based targeted DNA sequencing approach to sequence and identify genetic mutations in 91 human rectal cancer samples. Analysis revealed frequent mutations in KRAS (58.2%), TP53 (28.6%), APC (16.5%), FBXW7 (9.9%) and PIK3CA (9.9%), and additional mutations in BRAF, CTNNB1, ERBB2 and SMAD4 were also detected at lesser frequencies. Thirty eight samples (41.8%) also contained two or more mutations, with common combination mutations occurring between KRAS and TP53 (42.1%), and KRAS and APC (31.6%). DNA sequencing for individual cancers is of clinical importance for targeted drug therapy and the advantages of such targeted gene sequencing over other NGS platforms or commercially available kits in sensitivity, cost and time effectiveness may aid clinicians in treating CRC patients in the near future. PMID- 26134514 TI - GIGYF2 mutation in late-onset Parkinson's disease with cognitive impairment. AB - Although in the last two decades there has been considerable progress in understanding the genetic basis of Parkinson's disease (PD), the majority of PD is sporadic and its genetic causes are largely unknown. In an attempt to identify novel genetic causes of PD, whole-exome sequencing and subsequent analyses were performed in a family featuring late-onset PD with cognitive impairment. A novel genetic variant (p.Arg610Gly) in the GIGYF2 gene, previously known to be associated with PD, was identified as potential disease-causing mutation. The GIGYF2 p.Arg610Gly mutation situated in the GYF domain of the encoding protein was predicted to be pathogenic and to disrupt the GYF's ligand-binding abilities. Although further research is still required, this finding may shed light on the GIGYF2-associated mechanisms that lead to PD and suggests insulin dysregulation as a disease-specific mechanism for both PD and cognitive dysfunction. PMID- 26134516 TI - The role of matrix metalloproteinases and cysteine-cathepsins on the progression of dentine erosion. AB - OBJECTIVE: To evaluate in vitro the effect of the inhibition of endogenous dentinal enzymes (matrix metalloproteinases-MMPs and cysteine cathepsins-CCs) on dentine erosion. DESIGN: Dentine blocks (4mm*4mm*2mm) from sound human teeth were randomly divided into 7 groups (n=17) according to the treatment: MMP- and CC inhibitor chlorhexidine digluconate (CHX, 10mM); MMP-inhibitor galardin (G, 0.2mM); specific cathepsin B inhibitor (CCB, 0.2mM); non-specific CC inhibitor (CCE-64, 0.5MUM); fluoride (F, 1.23% NaF); placebo (P) and untreated (UT). Inhibitors were applied as gels once for 1min. Specimens were submitted to 5 days of pH cycling including the erosive challenge (Coke, pH 2.64, 90s/day) and remineralisation (artificial saliva). Demineralised organic surface loss was determined profilometrically. Demineralised organic matrix (DOM) was removed with collagenase and the profile was re-evaluated in the absence of collagen fibrils. The differences in profilometric results and DOM thickness among the groups were analysed with ANOVA and Tukey's test (p<0.05). RESULTS: Loss of demineralised tissue (MUm, mean+/-SD) was: CHX 8.4+/-1.7 b, G 8.6+/-1.9 b, CCB 9.6+/-1.4 a, CCE 64 9.9+/-1.3 a, F 9.9+/-1.7 a, P 10.9+/-2.2 a, UT 11.0+/-1.5 a. Loss of mineralised tissue was: CHX 15.4+/-2.2 b, G 16.0+/-1.8 b, CCB 17.6+/-2.4 a, CCE 64 17.6+/-2.0 a, F 17.3+/-2.8 a, P 19.1+/-2.1 a, UT 18.9+/-2.4 a. MMP-inhibitors significantly reduced organic matrix and mineral loss in comparison to all the other groups (p<0.05). No statistically significant differences were found in the thickness of the remaining DOM (p=0.845). CONCLUSION: Dentine endogenous MMPs seem to be the main enzymes responsible for DOM loss and erosion. PMID- 26134515 TI - Molecular genetics of coronary artery disease. AB - Coronary artery disease (CAD) including myocardial infarction (MI) is a common disease and among the leading cause of death in the world. The onset of CAD depends on complex interactions of environmental and genetic factors. To clarify the genetic architecture of MI, we started a genome-wide association study (GWAS) using nearly 100 000 gene-based single-nucleotide polymorphisms (SNPs) from 2000, and identified LTA associated with the increased risk of MI in Japanese population. To our knowledge, this is the first study identified a genetic factor for common disease by GWAS in the worldwide. Through examining the LTA cascade by combination of molecular biological and genetic analyses, we have identified additional MI susceptible genes, LGALS2, PSMA6 and BRAP, so far. Nowadays a lot of large-scale GWAS have identified numerous genetic risk factors for common diseases. In CAD, 51 loci with GWAS significance (P<5 * 10(-8)) have collectively identified by recent large-scale GWAS mainly in Caucasian descent. In this review, we discuss recent advances in molecular genetics for CAD. PMID- 26134517 TI - Lysophosphatidic acid increases the proliferation and migration of adipose derived stem cells via the generation of reactive oxygen species. AB - Phospholipid derivatives, such as lysophosphatidic acid (LPA), exhibit mitogenic effects on mesenchymal stem cells; however, the molecular mechanism underlying this stimulation has yet to be identified. The aims of the present study were as follows: To evaluate the stimulatory effects of LPA on the proliferation and migration of adipose-derived stem cells (ASCs); to study the association between reactive oxygen species (ROS) and LPA signaling in ASCs; and to investigate the microRNAs upregulated by LPA treatment in ASCs. The results of the present study demonstrated that LPA increased the proliferation and migration of ASCs, and acted as a mitogenic signal via extracellular signal-regulated kinases 1/2 and the phosphoinositide 3-kinase/Akt signaling pathways. The LPA1 receptor is highly expressed in ASCs, and pharmacological inhibition of it by Ki16425 significantly attenuated the proliferation and migration of ASCs. In addition, LPA treatment generated ROS via NADPH oxidase 4, and ROS were able to function as signaling molecules to increase the proliferation and migration of ASCs. The induction of ROS by LPA treatment also upregulated the expression of miR-210. A polymerase chain reaction array assay demonstrated that the expression levels of adrenomedullin and Serpine1 were increased following treatment with LPA. Furthermore, transfection with Serpine1-specific small interfering RNA attenuated the migration of ASCs. In conclusion, the present study is the first, to the best of our knowledge, to report that ROS generation and miR-210 expression are associated with the LPA-induced stimulation of ASCs, and that Serpine1 mediates the LPA-induced migration of ASCs. These results further suggest that LPA may be used for ASC stimulation during stem cell expansion. PMID- 26134518 TI - A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax. AB - Anthrax is a highly lethal infectious disease caused by the bacterium Bacillus anthracis, and the associated shock is closely related to the lethal toxin (LeTx) produced by the bacterium. The central role played by the 63 kDa protective antigen (PA63) region of LeTx in the pathophysiology of anthrax makes it an excellent therapeutic target. In the present study, a human/murine chimeric IgG mAb, hmPA6, was developed by inserting murine antibody variable regions into human constant regions using antibody engineering technology. hmPA6 expressed in 293F cells could neutralize LeTx both in vitro and in vivo. At a dose of 0.3 mg/kg, it could protect all tested rats from a lethal dose of LeTx. Even administration of 0.6 mg/kg hmPA6 48 h before LeTx challenge protected all tested rats. The results indicate that hmPA6 is a potential candidate for clinical application in anthrax treatment. PMID- 26134519 TI - A Fine Balance of Dietary Lipids Improves Pathology of a Murine Model of VCP Associated Multisystem Proteinopathy. AB - The discovery of effective therapies and of disease mechanisms underlying valosin containing protein (VCP)-associated myopathies and neurodegenerative disorders remains elusive. VCP disease, caused by mutations in the VCP gene, are a clinically and genetically heterogeneous group of disorders with manifestations varying from hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia (IBMPFD), and amyotrophic lateral sclerosis (ALS). In the present study, we examined the effects of higher dietary lipid percentages on VCPR155H/R155H, VCPR155H/+ and Wild Type (WT) mice from birth until 15 months of age by immunohistochemical and biochemical assays. Findings illustrated improvement in the muscle strength, histology, and autophagy signaling pathway in the heterozygote mice when fed 9% lipid-enriched diets (LED). However, increasing the LED by 12%, 30%, and 48% showed no improvement in homozygote and heterozygote survival, muscle pathology, lipid accumulation or the autophagy cascade. These findings suggest that a balanced lipid supplementation may have a therapeutic strategy for patients with VCP-associated multisystem proteinopathies. PMID- 26134521 TI - Altered expression of the PLAGL1 (ZAC1/LOT1) gene in colorectal cancer: Correlations to the clinicopathological parameters. AB - Pleomorphic adenoma gene-like 1 gene (PLAGL1) encodes a zinc-finger nuclear transcription factor which promotes apoptosis and cell cycle arrest. Loss or downregulation of its expression has been observed in various human neoplasms. This study compared PLAGL1 expression in colorectal cancer (CRC) tissue and colon mucosa of healthy subjects at the mRNA and protein levels, and estimated its prognostic value. The PLAGL1 mRNA levels were also determined in CRC cell lines. We collected paired tumor tissue and unchanged mucosa of the large intestine from 121 CRC patients as well as 72 colon biopsies of healthy subjects obtained during screening colonoscopy. PLAGL1 mRNA levels were determined by quantitative PCR, while PLAGL1 protein expression was estimated by western blotting and immunohistochemistry. PLAGL1 mRNA level in tumor tissue was ~2-fold lower than in samples of corresponding unchanged tissues and biopsies of healthy colon mucosa. Downregulated expression of PLAGL1 mRNA was also observed in all tested CRC cell lines. Although the average content of PLAGL1 protein did not differ significantly between tumor and unchanged tissues of CRC patients or colon mucosa of healthy individuals, the decreased PLAGL1 protein levels in tumor specimens correlated with lymph node involvement, the presence of metastases and higher TNM disease stage. The PLAGL1 expression level did not correlate significantly with patient overall survival; however, the hazard ratio for patients whose tumor tissues showed reduced PLAGL1 immunohistochemical staining was twice higher than in patients with increased PLAGL1 immunoreactivity. In conclusion, these results suggest that dysregulation of PLAGL1 expression may be involved to some extent in the progression of CRC, but the so far collected patient survival data do not confirm applicability of the PLAGL1 expression level as a prognostic factor in CRC. PMID- 26134520 TI - Crystallographic structure of a small molecule SIRT1 activator-enzyme complex. AB - SIRT1, the founding member of the mammalian family of seven NAD(+)-dependent sirtuins, is composed of 747 amino acids forming a catalytic domain and extended N- and C-terminal regions. We report the design and characterization of an engineered human SIRT1 construct (mini-hSIRT1) containing the minimal structural elements required for lysine deacetylation and catalytic activation by small molecule sirtuin-activating compounds (STACs). Using this construct, we solved the crystal structure of a mini-hSIRT1-STAC complex, which revealed the STAC binding site within the N-terminal domain of hSIRT1. Together with hydrogen deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis using full-length hSIRT1, these data establish a specific STAC-binding site and identify key intermolecular interactions with hSIRT1. The determination of the interface governing the binding of STACs with human SIRT1 facilitates greater understanding of STAC activation of this enzyme, which holds significant promise as a therapeutic target for multiple human diseases. PMID- 26134522 TI - Non-Native Ambrosia Beetles as Opportunistic Exploiters of Living but Weakened Trees. AB - Exotic Xylosandrus spp. ambrosia beetles established in non-native habitats have been associated with sudden and extensive attacks on a diverse range of living trees, but factors driving their shift from dying/dead hosts to living and healthy ones are not well understood. We sought to characterize the role of host physiological condition on preference and colonization by two invaders, Xylosandrus germanus and Xylosandrus crassiusculus. When given free-choice under field conditions among flooded and non-flooded deciduous tree species of varying intolerance to flooding, beetles attacked flood-intolerant tree species over more tolerant species within 3 days of initiating flood stress. In particular, flood intolerant flowering dogwood (Cornus florida) sustained more attacks than flood tolerant species, including silver maple (Acer saccharinum) and swamp white oak (Quercus bicolor). Ethanol, a key host-derived attractant, was detected at higher concentrations 3 days after initiating flooding within stems of flood intolerant species compared to tolerant and non-flooded species. A positive correlation was also detected between ethanol concentrations in stem tissue and cumulative ambrosia beetle attacks. When adult X. germanus and X. crassiusculus were confined with no-choice to stems of flood-stressed and non-flooded C. florida, more ejected sawdust resulting from tunneling activity was associated with the flood-stressed trees. Furthermore, living foundresses, eggs, larvae, and pupae were only detected within galleries created in stems of flood-stressed trees. Despite a capability to attack diverse tree genera, X. germanus and X. crassiusculus efficiently distinguished among varying host qualities and preferentially targeted trees based on their intolerance of flood stress. Non flooded trees were not preferred or successfully colonized. This study demonstrates the host-selection strategy exhibited by X. germanus and X. crassiusculus in non-native habitats involves detection of stress-induced ethanol emission and early colonization of living but weakened trees. PMID- 26134524 TI - Amphiphilic zein hydrolysate as a novel nano-delivery vehicle for curcumin. AB - In this paper, we developed amphiphilic zein hydrolysate (ZH) as a novel delivery vehicle, which could be used for preparing curcumin (Cur) nanocomplexes. These ZH Cur nanocomplexes exhibited spherical morphology with a monodisperse size distribution (<50 nm), and the dispersion was transparent, which could have a great application potential in nutraceutical-fortified food and clear beverages. The water solubility of curcumin was considerably enhanced by the nanocomplexation above 8200-fold (vs. free curcumin in water). The good colloidal and storage stability of ZH-Cur nanocomplexes was greatly improved, and more than 60% of curcumin was retained in 72 h storage under ambient conditions. These phenomena appeared to be attributable to the fact that amphiphilic ZH displayed self-assembly properties in water solution and strong interfacial activity at the oil-water interface, as confirmed by micelle formation and dynamic interfacial adsorption respectively. Fluorescence titration and FTIR results indicated the existence of strong hydrophobic interactions between ZH and Cur, which was responsible for the complexation. PMID- 26134523 TI - Hansenula polymorpha Pmt4p Plays Critical Roles in O-Mannosylation of Surface Membrane Proteins and Participates in Heteromeric Complex Formation. AB - O-mannosylation, the addition of mannose to serine and threonine residues of secretory proteins, is a highly conserved post-translational modification found in organisms ranging from bacteria to humans. Here, we report the functional and molecular characterization of the HpPMT4 gene encoding a protein O mannosyltransferase in the thermotolerant methylotrophic yeast Hansenula polymorpha, an emerging host for the production of therapeutic recombinant proteins. Compared to the deletion of HpPMT1, deletion of another major PMT gene, HpPMT4, resulted in more increased sensitivity to the antibiotic hygromycin B, caffeine, and osmotic stresses, but did not affect the thermotolerance of H. polymorpha. Notably, the deletion of HpPMT4 generated severe defects in glycosylation of the surface sensor proteins HpWsc1p and HpMid2p, with marginal effects on secreted glycoproteins such as chitinase and HpYps1p lacking a GPI anchor. However, despite the severely impaired mannosylation of surface sensor proteins in the Hppmt4? mutant, the phosphorylation of HpMpk1p and HpHog1p still showed a high increase upon treatment with cell wall disturbing agents or high concentrations of salts. The conditional Hppmt1pmt4? double mutant strains displayed severely impaired growth, enlarged cell size, and aberrant cell separation, implying that the loss of HpPMT4 function might be lethal to cells in the absence of HpPmt1p. Moreover, the HpPmt4 protein was found to form not only a homomeric complex but also a heteromeric complex with either HpPmt1p or HpPmt2p. Altogether, our results support the function of HpPmt4p as a key player in O mannosylation of cell surface proteins and its participation in the formation of heterodimers with other PMT members, besides homodimer formation, in H. polymorpha. PMID- 26134525 TI - Tinkering signaling pathways by gain and loss of protein isoforms: the case of the EDA pathway regulator EDARADD. AB - BACKGROUND: Only a handful of signaling pathways are major actors of development and responsible for both the conservation and the diversification of animal morphologies. To explain this twofold nature, gene duplication and enhancer evolution were predominantly put forth as tinkering mechanisms whereas the evolution of alternative isoforms has been, so far, overlooked. We investigate here the role of gain and loss of isoforms using Edaradd, a gene of the Ecodysplasin pathway, implicated in morphological evolution. A previous study had suggested a scenario of isoform gain and loss with an alternative isoform (A) newly gained in mammals but secondarily lost in mouse lineage. RESULTS: For a comprehensive view of A and B Edaradd isoforms history during mammal evolution, we obtained sequences for both isoforms in representative mammals and performed in vitro translations to support functional predictions. We showed that the ancestral B isoform is well conserved, whereas the mammal-specific A isoform was lost at least 7 times independently in terminal lineages throughout mammal phylogeny. Then, to gain insights into the functional relevance of this evolutionary pattern, we compared the biological function of these isoforms: i) In cellulo promoter assays showed that they are transcribed from two alternative promoters, only B exhibiting feedback regulation. ii) RT-PCR in various tissues and ENCODE data suggested that B isoform is systematically expressed whereas A isoform showed a more tissue-specific expression. iii) Both isoforms activated the NF-kappaB pathway in an in cellulo reporter assay, albeit at different levels and with different dynamics since A isoform exhibited feedback regulation at the protein level. Finally, only B isoform could rescue a zebrafish edaradd knockdown. CONCLUSIONS: These results suggest that the newly evolved A isoform enables modulating EDA signaling in specific conditions and with different dynamics. We speculate that during mammal diversification, A isoform regulation may have evolved rapidly, accompanying and possibly supporting the diversity of ectodermal appendages, while B isoform may have ensured essential roles. This study makes the case to pay greater attention to mosaic loss of evolutionarily speaking "young" isoforms as an important mechanism underlying phenotypic diversity and not simply as a manifestation of neutral evolution. PMID- 26134526 TI - Morphological and Molecular Revision of the Genus Ozirhincus (Diptera: Cecidomyiidae)-Long-Snouted Seed-Feeding Gall Midges on Asteraceae. AB - The Palaearctic gall-midge genus Ozirhincus is unique among the Cecidomyiidae for its morphology and biology. Unlike most other phytophagous gall midges, species in this genus do not induce galls but develop inside achenes of Asteraceae plants. The heads of adults are characterized by an unusually elongate proboscis, the function of which is unclear. Despite a lot of attention from taxonomists in the 19th and early 20th century, a proper revision of the genus has been hindered by complex host associations, the loss of most relevant type material, and the lack of a thorough comparative study of all life stages. The present revision integrated morphological, molecular, and life-history data to clearly define species boundaries within Ozirhincus, and delimit host-plant ranges for each of them. A phylogenetic analysis based on the mitochondrial COI and 16S genes confirmed the validity of four distinct species but did not resolve the relationships among them. All species are oligophages, and some may occur together on the same host plant. Species with wider host-plant ranges have wider European and circum-Mediterranean distribution ranges, whereas species with narrower host ranges are limited to Europe and the Russian Far East. As part of the present work, O. hungaricus is reinstated from synonymy, O. tanaceti is synonymized under O. longicollis, neotypes are designated for O. longicollis and O. millefolii, and a lectotype is designated for O. anthemidis. PMID- 26134527 TI - Incidence and Burden of the Myelodysplastic Syndromes. AB - Since 2001, cases of myelodysplastic syndromes (MDSs) have been tracked by cancer registries. Examining registry data in the USA, the reported age-adjusted incidence of MDS per 100,000 was 3.3 per year for 2001-2003 and 4.9 per year for 2007-2011, with increases likely a result of growing awareness of reporting requirements. However, active case-finding methods repeatedly demonstrate that population-based registries have underestimated the incidence of MDS due to underreporting and underdiagnosis. Using keyword search strategies of electronic pathology reports or other novel case capture methods, the true incidence of MDS has been estimated between 5.3 and 13.1 per 100,000. Using Medicare billing claims data, the incidence of MDS per 100,000 in patients aged >=65 years has been estimated between 75 and 162. MDS prevalence is estimated to be 60,000 and 170,000 in the USA and projected to grow. Epidemiologic data can help estimate the burden of MDS and expose unmet clinical needs. For example, patients with MDS receiving transfusions had significantly higher reported health care costs versus those that did not (3-year mean of $88,824 vs $29,519). Epidemiologic data also revealed that most MDS patients receiving transfusions do not receive active therapies, despite strong evidence that hypomethylating agents and lenalidomide significantly reduce transfusion burden. Other unmet needs identified by epidemiologic studies include high need for treatment options after failing first line therapy and shared decision making by older MDS patients. PMID- 26134528 TI - Kidney diseases and tissue engineering. AB - Kidney disease is a worldwide public health problem. Renal failure follows several disease stages including acute and chronic kidney symptoms. Acute kidney injury (AKI) may lead to chronic kidney disease (CKD), which can progress to end stage renal disease (ESRD) with a mortality rate. Current treatment options are limited to dialysis and kidney transplantation; however, problems such as donor organ shortage, graft failure and numerous complications remain a concern. To address this issue, cell-based approaches using tissue engineering (TE) and regenerative medicine (RM) may provide attractive approaches to replace the damaged kidney cells with functional renal specific cells, leading to restoration of normal kidney functions. While development of renal tissue engineering is in a steady state due to the complex composition and highly regulated functionality of the kidney, cell therapy using stem cells and primary kidney cells has demonstrated promising therapeutic outcomes in terms of restoration of renal functions in AKI and CKD. In this review, basic components needed for successful renal kidney engineering are discussed, and recent TE and RM approaches to treatment of specific kidney diseases will be presented. PMID- 26134529 TI - Colonization by fragments of the submerged macrophyte Myriophyllum spicatum under different sediment type and density conditions. AB - In this paper, the effect of plant density, sediment type, and macrophyte fragment size on the fragment colonization ability of Myriophyllum spicatum was evaluated in an outdoor experiment. The relative growth rate (RGR) was higher in the mud and low-density treatments than in the sand and high-density treatments. The relative elongation rate (RER) decreased with increasing density and fragment size, with RER values being much higher in the mud than the sand treatments. Both branching number and shoot diameter increased with decreasing density and increasing fragment size, and were significantly higher in the mud than the sand treatments. The shoot : root ratio was higher in the mud treatments than in the sand treatments. Total N content in both the shoot and root was significantly higher in the mud and low-density treatments than in the sand and high-density treatments. Shoot P content only decreased with increasing density, while root P content was higher in the mud and low-density treatments than in the sand and high-density treatments. These data indicate that fragment colonization by M. spicatum is improved by large fragments, low density, and nutrient-rich sediments, and that these conditions contribute to the rapid population expansion of this species. PMID- 26134531 TI - Body Size, Bone Mineral Density, and Body Composition in Obese Women After Laparoscopic Sleeve Gastrectomy: A 1-Year Longitudinal Study. AB - Changes in body weight, waist and hip circumferences, body composition, and skeletal status in women after bariatric surgery were evaluated. Thirty-six women [mean age 41.2 +/- (SD) 9.5 years, weight 115.7+/-18.0 kg, and BMI 42.1+/-5.3 kg/m(2)] underwent laparoscopic sleeve gastrectomy. Bone mineral density (BMD) at lumbar spine, femoral neck, total hip, and total body, and body composition were evaluated at baseline and 3, 6, and 12 months after surgery.Weight, BMI, waist and hip circumferences decreased significantly. Total body bone mineral content (TBBMC) increased by 2.5+/-3.5%, and fat, lean body mass, total mass and fat-% decreased significantly by 38.9+/-12.0%, 15.4+/-5.9%, 26.5+/-8.1%, and 17.6+/ 8.9%, respectively. Slight decreases in total body (0.6+/-2.2%) and spine (1.2+/ 7.1%) BMD were not significant, whereas total hip and femoral neck BMD decreased significantly by 5.3+/-8.2%, and 6.2+/-7.0% (p<0.001). Change (Delta) in TBBMC correlated only with Delta in weight (r=0.38, p<0.05) whereas Delta in all other body composition parameters correlated significantly with Delta in body weight and circumferences (r=0.46-0.98). The Delta in BMD (except total body BMD) correlated significantly with Delta in body composition parameters (r=0.34-0.59). Baseline fat and lean content besides changes in body fat and lean mass accounted for bone changes. In conclusion, bone loss after bariatric surgery is related to post-operative changes in body composition, as well as to weight loss and decrease in waist and hip circumferences. PMID- 26134530 TI - Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA. AB - Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here, we identify post-transcriptional mechanisms that help enforce a cell-cycle arrest in Caulobacter crescentus following nutrient limitation and during entry into stationary phase by limiting the accumulation of DnaA, the conserved replication initiator protein. DnaA is rapidly degraded by the Lon protease following nutrient limitation. However, the rate of DnaA degradation is not significantly altered by changes in nutrient availability. Instead, we demonstrate that decreased nutrient availability downregulates dnaA translation by a mechanism involving the 5' untranslated leader region of the dnaA transcript; Lon-dependent proteolysis of DnaA then outpaces synthesis, leading to the elimination of DnaA and the arrest of DNA replication. Our results demonstrate how regulated translation and constitutive degradation provide cells a means of precisely and rapidly modulating the concentration of key regulatory proteins in response to environmental inputs. PMID- 26134532 TI - Comparison Between Subtotal Parathyroidectomy and Total Parathyroidectomy with Autotransplantation for Secondary Hyperparathyroidism in Patients with Chronic Renal Failure: A Meta-Analysis. AB - We conducted a meta-analysis of randomized and 2-arm prospective or retrospective studies that compared the efficacy of PTX and TPTX+AT in patients with medically uncontrollable secondary HPT due to chronic renal failure. Citations were identified in the Medline, Cochrane, EMBASE, and Google Scholar databases through April 2014. The primary outcome of interest was HPT recurrence rate, while secondary outcomes included changes in serum calcium (Ca(++ )), parathyroid hormone (PTH), alkaline phosphatase (ALP), and phosphate (P) levels. Five studies were included in the present analysis. The NOS score of all the included studies was 7 or above, and heterogeneity among the studies was minimal for 3 of the 5 outcomes. The HPT recurrence rate was similar for patients who underwent SPTX vs. TPTX+AT [odds ratio (OR)=0.825; 95% confidence interval (CI)=0.368 to 1.846; p=0.639]. The changes in serum Ca(++ ), PTH, ALP, and P were also similar between the 2 treatment groups (Ca(++ ): Std diff in means=- 0.166; 95% CI=- 0.703 to 0.371; p=0.545; PTH: pooled diff in means=561.17; 95% CI=-174.30 to 1296.6; p=0.135; ALP: pooled diff in means=0.58; 95% CI=- 70.07 to 71.24; p=0.987; P: pooled Std diff in means=0.26; 95% CI=- 0.091 to 0.630; p=0.143). Our findings indicate that SPTX and TPTX+AT are equally successful in preventing recurrent HPT and improving secondary HPT. We therefore, conclude that the choice of procedure can be left to the surgeons. PMID- 26134533 TI - Endogenous acetylcholine increases alveolar epithelial fluid transport via activation of alveolar epithelial Na,K-ATPase in mice. AB - The contribution of endogenous acetylcholine to alveolar fluid clearance (AFC) and related molecular mechanisms were explored. AFC was measured in Balb/c mice after vagotomy and vagus nerve stimulation. Effects of acetylcholine chloride on AFC in Kunming mice and Na,K-ATPase function in A549 alveolar epithelial cells also were determined. AFC significantly decreased in mice with left cervical vagus nerve transection compared with controls (48.69 +/- 2.57 vs. 66.88 +/- 2.64, P <= 0.01), which was reversed by stimulation of the peripheral (60.81 +/- 1.96, P <= 0.01). Compared with control, acetylcholine chloride dose-dependently increased AFC and elevated Na,K-ATPase activity, and these increases were blocked or reversed by atropine. These effects were accompanied by recruitment of Na,K ATPase alpha1 to the cell membrane. Thus, vagus nerves participate in alveolar epithelial fluid transport by releasing endogenous acetylcholine in the infusion induced pulmonary edema mouse model. Effects of endogenous acetylcholine on AFC are likely mediated by Na,K-ATPase function through activation of muscarinic acetylcholine receptors on alveolar epithelia. PMID- 26134534 TI - Detection and Enumeration of Streptococcus agalactiae from Bovine Milk Samples by Real-Time Polymerase Chain Reaction. AB - The aim of this study was to evaluate the use of real-time polymerase chain reaction (qPCR) combined with DNA extraction directly from composite milk and bulk tank samples for detection and enumeration of Streptococcus agalactiae (SAG) causing subclinical mastitis. Dilutions of sterile reconstituted skim milk inoculated with SAG ATCC 13813 were used to establish a standard curve (cfu/mL) for the qPCR assay targeting SAG. The analytical sensitivity and repeatability of the qPCR assay were determined. Bulk tank (BTM; n = 38) and composite milk samples (CM; n = 26) collected from lactating cows with positive isolation of SAG were submitted to the qPCR protocol and SAG plate counting, with results from both methods compared. Amplification of DNA was not possible in two out of 64 samples, indicating that qPCR was able to detect SAG in 96 and 97% of BTM and CM samples, respectively. The inter-assay coefficient of variation was <5%, showing that the technique had adequate repeatability. The qPCR protocol can be a high throughput and rapid diagnostic assay to accurately detect SAG from BTM and CM samples compared with conventional microbiological culture method. However, the evaluated qPCR protocol is not accurate for enumerating SAG in milk samples, probably due to quantification of DNA of non-viable cells. PMID- 26134535 TI - Halorientalis brevis sp. nov., Isolated from an Inland Salt Lake of China. AB - Halophilic archaeal strain YC89(T) was isolated from Yuncheng salt lake in Shanxi, China. Cells from strain YC89(T) were short rods, lysed in distilled water, stained Gram-negative and formed red-pigmented colonies on agar plate. Strain YC89(T) was able to grow at 25-50 degrees C (optimum 37 degrees C), at 1.4 4.8 M NaCl (optimum 2.6-3.1 M), at 0-1.0 M MgCl2 (optimum 0.3 M) and at pH 6.0 9.5 (optimum pH 7.5). The major polar lipids are phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, sulfated mannosyl glucosyl diether and two unknown glycolipids. 16S rRNA gene analysis revealed that strain YC89(T) was phylogenetically related to Halorientalis persicus D108(T) (95.6% nucleotide identity) and H. regularis TNN28(T) (95.3% nucleotide identity). The rpoB' gene similarities between strain YC89(T) and H. persicus IBRC-M 10043(T) and H. regularis TNN28(T) were 88.1 and 88.0%, respectively. The DNA G+C content of strain YC89(T) was determined to be 61.3 mol%. The phenotypic, chemotaxonomic and phylogenetic properties suggested that strain YC89(T) (=CGMCC 1.12125(T) = JCM 18366(T)) represents a new species of Halorientalis, for which the name H. brevis sp. nov. is proposed. PMID- 26134536 TI - Development and Evaluation of qPCR Assay for Quantitation of Kazachstania slooffiae and Total Yeasts Occurring in the Porcine Gut. AB - Kazachstania slooffiae is the dominating yeast in pig's gut. No methods others than cultivation were applied for enumeration of yeasts within this ecosystem. Therefore, the aim of this study was to develop a real-time quantitative polymerase chain reaction (qPCR) assay to quantitate total yeasts and K. slooffiae in the porcine gut. This work demonstrated that the copy numbers in gDNA can be determined by qPCR using PCR amplicons as a calibrator and one-point calibration method. The gDNA were then used as a calibrator for further analysis. The values of quantitation cycle and PCR amplification efficiency of gDNA calibrator were highly reproducible. DNA was extracted from feces and from 10 different cultured yeasts found in pigs' intestine. The qPCR results using primers NL1/LS2 encoding 26S rDNA correlated (r = 0.984, P < 0.0001) with cultivation results. From two primer sets developed, one set encoding act1 gene was suitable for quantitation of K. slooffiae. The copy numbers of K. slooffiae could be determined by 40% analyzed animals, amounting to about 70% of total yeasts. The application of this method in next studies will help to get more information about K. slooffiae and total yeasts in the gut of pigs. PMID- 26134537 TI - Recent status of organohalogens, heavy metals and PAHs pollution in specific locations in India. AB - Our group of scientists at the Center for Marine Environmental Studies (CMES), Ehime University, Japan has been carrying-out studies in India from the 1980s on chemicals contamination. Due to its agrarian economy, use of fossil fuels, industries, growing population and urbanization, chemicals such as pesticides, dioxins and related chemicals (DRCs), brominated flame retardants (BFRs), heavy metals, and polyaromatic hydrocarbons (PAHs) are widely spread in India. We have published a review (Subramanian and Tanabe, 2007) covering papers published until 2005, on India. A decade had passed and this is the time to provide an update of the spatial and temporal changes during this period and hence this review. At many instances organochlorines such as DDTs and HCHs showed decreasing trends even though they are still at considerable levels. Novel chemicals such as PCDDs/Fs are seen at municipal solid waste dumping sites of India at levels equivalent to similar locations of the developed world. In the e-waste processing sites in India, especially the informal ones, apart from PCDDs/Fs, some brominated flame retardants (BFRs) and heavy metals were present as contaminants. Metro cities of India showed location specific contamination by HCHs, DDTs, PCDDs/Fs, BFRs, PAHs, etc. Coastal regions of India seem to be still unpolluted when compared to the nearby inland locations. This review is concerned mainly with the chemicals that we (CMES) have been evaluating in India in the past three decades. We suggest the importance of further studies, future directions for policy decisions and also for implementing control measures. PMID- 26134538 TI - Assessment of PCDD/Fs formation in the Fenton oxidation of 2-chlorophenol: Influence of the iron dose applied. AB - Toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) may be formed during remediation of chlorinated phenols via Fenton oxidation. To highlight the need for monitoring the production of toxic byproducts in these reactions, this work assessed the influence of iron dose (0.09-0.36 mM) on the Fenton oxidation of 2-chlorophenol (2-CP, 15.56 mM), a potential precursor of PCDD/Fs, by quantifying 2-CP removal and mineralization rates as well as byproducts yields, including PCDD/Fs. Although the increase in the iron dose showed positive contribution to 2-CP oxidation, under the operating conditions of the current study (H2O2 at 20% of the stoichiometric dose and 20 degrees C), there was no effect on the mineralization rate, and TOC and chlorine balances were far to be closed, depicting the presence of chlorinated organic byproducts in the reaction medium. After 4 h of treatment, the total PCDD/Fs concentrations increased by 14.5-39 times related to the untreated sample when the iron doses tested decreased from 0.36 to 0.09 mM, with preferential formation of PCDFs over PCDDs and dominance of lower chlorinated congeners such as tetra and penta-PCDD/Fs. The treatment with the highest iron dose (0.36 mM) exhibited the lowest PCDD/Fs yields and was thus most successful at mitigating toxic byproducts of the Fenton oxidation, leading to lower sample toxic equivalence (TEQ) value. PMID- 26134540 TI - Phenotypic variation and covariation indicate high evolvability of acoustic communication in crickets. AB - Studying the genetic architecture of sexual traits provides insight into the rate and direction at which traits can respond to selection. Traits associated with few loci and limited genetic and phenotypic constraints tend to evolve at high rates typically observed for secondary sexual characters. Here, we examined the genetic architecture of song traits and female song preferences in the field crickets Gryllus rubens and Gryllus texensis. Song and preference data were collected from both species and interspecific F1 and F2 hybrids. We first analysed phenotypic variation to examine interspecific differentiation and trait distributions in parental and hybrid generations. Then, the relative contribution of additive and additive-dominance variation was estimated. Finally, phenotypic variance-covariance (P) matrices were estimated to evaluate the multivariate phenotype available for selection. Song traits and preferences had unimodal trait distributions, and hybrid offspring were intermediate with respect to the parents. We uncovered additive and dominance variation in song traits and preferences. For two song traits, we found evidence for X-linked inheritance. On the one hand, the observed genetic architecture does not suggest rapid divergence, although sex linkage may have allowed for somewhat higher evolutionary rates. On the other hand, P matrices revealed that multivariate variation in song traits aligned with major dimensions in song preferences, suggesting a strong selection response. We also found strong covariance between the main traits that are sexually selected and traits that are not directly selected by females, providing an explanation for the striking multivariate divergence in male calling songs despite limited divergence in female preferences. PMID- 26134541 TI - Indications and risk factors for midurethral sling revision. AB - INTRODUCTION AND HYPOTHESIS: To determine the indications and risk factors for needing midurethral sling revision in a cohort of women undergoing midurethral sling placement. METHODS: This was a case-control study of all women undergoing midurethral sling placement for stress urinary incontinence (SUI) between January 2003 and December 2013. Cases were patients who underwent midurethral sling placement followed by sling revision (incision, partial or complete excision). Controls were patients who underwent sling placement only. Once all subjects had been identified, the electronic medical record was queried for demographic and perioperative and postoperative data. RESULTS: Of 3,307 women who underwent sling placement, 89 (2.7%, 95% CI 1.9 - 3.4) underwent sling revision for one or more of the following indications: urinary retention (43.8%), voiding dysfunction (42.7%), recurrent urinary tract infection (20.2%), mesh erosion (21.3%), vaginal pain/dyspareunia (7.9%), and groin pain (3.4%). The median time from the index to the revision surgery was 7.8 months (2.3 - 17.9 months), but was significantly shorter in patients with urinary retention. The type of sling placed (retropubic or transobturator) was not associated with indication for revision. Patients who underwent revision surgery were more likely to have had previous SUI surgery (adjusted odds ratio 4.4, 95% CI 1.7 - 6.5) and to have undergone concomitant vaginal apical suspension (adjusted odds ratio 2.4, 95% CI 1.4 - 4.5). CONCLUSIONS: The rate of sling revision after midurethral sling placement was 2.7%. Urinary retention and voiding dysfunction were the most common indications. Patients with a history of previous SUI surgery and concomitant apical suspension at the time of sling placement may be at higher risk of requiring revision surgery. PMID- 26134542 TI - Astrocyte elevated gene-1 regulates CCL3/CCR5-induced epithelial-to-mesenchymal transition via Erk1/2 and Akt signaling in cardiac myxoma. AB - In recent years, astrocyte elevated gene-1 (AEG-1) has been reported as a key mediator that is involved in the epithelial-to-mesenchymal transition (EMT) process. However, the mechanisms underlying CCL3/CCR5-AEG-1 pathway-mediated EMT in cardiac myxoma (CM) has not been well featured till now. We used immnohistochemistry and immunoblotting to assess the expression of CCR5 and AEG-1 in 30 cases of CM tissues and cells. Subsequently, cultured CM cells were treated with si-AEG-1 or si-CCR5 and then subjected to in vitro assays. We observed that CCR5 and AEG-1 proteins were highly expressed in CM tissues (73.3 and 76.7%, respectively) and closely correlated with tumor size (>5 cm). Importantly, we validated the expression of AEG-1, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 increased in the CM cell with CCL3 treatment in a time- and concentration dependent manner. When CM cells were treated with si-CCR5, the expression of AEG 1, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 was downregulated. In addition, when CM cells were treated with si-AEG-1, the expression of p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 was also downregulated. Using the cell cycle and proliferation assay, the knockdown of AEG-1 inhibited the entry of G1 into S phase and the proliferation capacity of CM cells. In conclusion, AEG-1 mediates CCL3/CCR5-induced EMT development via both Erk1/2 and Akt signaling pathway in CM patients, which indicates CCL3/CCR5-AEG-1-EMT pathway could be suggested as a useful target to affect the progression of CM. PMID- 26134543 TI - Exogenous and endogenous shifts of attention in perihand space. AB - While some studies have found that attentional orienting is altered in perihand space, most have not. One reason for such discrepancies may be related to the types of cues (uninformative and informative) that have been used, as they are known to induce different types of shifts of attention (exogenous and endogenous, respectively). To systematically address this question, two experiments were performed in which an uninformative peripheral cue (Experiment 1) or an informative central cue (Experiment 2) preceded a peripheral target with a short (100-150 ms) stimulus-onset asynchrony. Participants performed the task with their left hand, right hand, both hands, or no hands near the display. Cueing effects were obtained in both experiments, but they were only modulated by hand position in Experiment 1, with larger effects observed in the right- and both hand conditions. These findings suggest that exogenous attention shifts are affected by hand proximity, while endogenous shifts are not. PMID- 26134544 TI - Newborn Readmissions to Slovenian Children's Hospitals in One Summer Month and One Autumn Month: A Retrospective Study. AB - BACKGROUND: With the shortening length of stay of newborns in hospitals after birth, concerns have been raised about the possible rise in readmission rates. In Slovenia, where the normal length of stay is 3 days, no data on readmissions were available. We sought to determine the frequency and causes for readmissions. METHODS: We conducted a retrospective study on all newborns readmitted to Slovenian children's hospitals and wards in June 2012 and November 2012. We obtained basic demographic data for newborns and mothers, analyzed the frequency of diagnoses, and compared the duration of treatment between summer months and autumn months. RESULTS: The proportion of readmissions in June 2012 and November 2012 was 6% and 5.9%, respectively. Around 10% more boys were readmitted in June 2012 and November 2012. In June 2012, the mean age was 12.2 days, and the mean birth weight was 3444 g. In November, the mean age was 10.5 days, and the mean birth weight was 3271 g. Around 50% of mothers were primiparous, and their mean age was around 31 years. Most received > 10 prenatal check-ups and participated in a prenatal class. The most common diagnosis in June 2012 and November 2012 was jaundice. The duration of treatment did not statistically significantly differ between summer months and autumn months, but it was associated with the admission diagnosis and infants' characteristics. CONCLUSION: Our study showed that the readmission rate in Slovenia was much higher than in some other developed countries. Prospective studies are needed to further confirm the findings and highlight the possible causes for this observation. PMID- 26134545 TI - "A world crazier than us": Vanishing social contexts and the consequences for psychiatric practice in contemporary Romania. AB - Since the end of Communism, mental health care in Romania has increasingly sought to align its practices with idealized models of Western psychiatric practice. Much of this realignment has been made possible by accessing and integrating new pharmaceuticals into psychiatric hospital settings. Less straightforward have been the painful attempts to create a system modeled on international standards for training and certifying psychotherapists. Unfortunately, the political, economic, infrastructural, and epistemological environment of the Romanian mental health care system has prevented many other reforms. This paper examines the ironic trajectory that Romanian psychiatry has taken since the end of state socialism. Specifically, this paper shows how psychiatric practice in most places (outside of university-training hospitals) is increasingly disconnected from a concern with the social conditions that surround mental illness during a period when social upheaval is profoundly impacting the lives of many people who receive mental health care. Thus, as the contribution of social problems to the suffering of those with mental illnesses has increased, some Romanian mental health practitioners have moved away from a concern with these social problems under the guise of aligning their psychiatric practices with (imagined) Western standards of biomedical care. The paper provides a brief history of Romanian psychiatry and explores contemporary challenges and contradictions in many Romanian psychiatric treatment settings through the case study of a 31-year-old Romanian female diagnosed with paranoid schizophrenia. PMID- 26134546 TI - How do health care organizations take on best practices? A scoping literature review. AB - AIMS: The aims of this scoping literature review are to examine and summarize the organizational-level factors, context, and processes that influence the use of evidence-based practice in healthcare organizations. METHODS: A scoping literature review was done to answer the question: What is known from the existing empirical literature about factors, context, and processes that influence the uptake, implementation, and sustainability of evidence-based practice in healthcare organizations? This review used the Arksey and O'Malley framework to describe findings and to identify gaps in the existing research literature. Inclusion and exclusion criteria were developed to screen studies. Relevant studies published between January 1991 and March 2014 were identified using four electronic databases. Study abstracts were screened for eligibility by two reviewers. Following this screening process, full-text articles were reviewed to determine the eligibility of the studies by the primary author. Eligible studies were then analyzed by coding findings with descriptive labels to distinguish elements that appeared relevant to this literature review. Coding was used to form categories, and these categories led to the development of themes. RESULTS: Thirty studies met the eligibility criteria for this literature review. The themes identified were: the process organizations use to select evidence based practices for adoption, use of a needs assessment, linkage to the organization's strategic direction, organizational culture, the organization's internal social networks, resources (including education and training, presence of information technology, financial resources, resources for patient care, and staff qualifications), leadership, the presence of champions, standardization of processes, role clarity of staff, and the presence of social capital. CONCLUSION: Several gaps were identified by this review. There is a lack of research on how evidence-based practices may be sustained by organizations. Most of the research done to date has been cross-sectional. Longitudinal research would give insight into the relationship between organizational characteristics and the uptake, implementation, and sustainability of evidence-based practice. In addition, although it is clear that financial resources are required to implement evidence based practice, existing studies contain a lack of detail about the cost of adopting and using new practices. This scoping review contains a number of implications for healthcare administrators, managers, and providers to consider when adopting and implementing evidence-based practices in healthcare organizations. PMID- 26134547 TI - The association of dietary intake and supplementation of specific polyunsaturated fatty acids with inflammation and functional capacity in chronic obstructive pulmonary disease: a systematic review. AB - OBJECTIVE: This systematic review sought to identify the association of dietary intake and supplementation of specific polyunsaturated fatty acids with inflammation and function in people with chronic obstructive pulmonary disease (COPD). DATA SOURCES: We searched electronic databases including PubMed, CINAHL, MEDLINE, EMBASE, The Cochrane Library, ProQuest Dissertations and Theses, Scopus, Google Scholar, Trove, and WHO International Clinical Trials Registry Platform and reference lists of retrieved articles published prior to August 2014. INCLUSION CRITERIA: We considered observational studies that evaluated dietary intake of omega-3 (eicosapentaenoic acid, docosahexaenoic acid or alpha-linolenic acid) and/or omega-6 fatty acids (gamma-linoleic acid or arachidonic acid), and experimental studies that evaluated omega-3 fatty acid supplementation (containing predominantly one or more omega-3 fatty acids) on airway and systemic inflammatory markers and/or functional capacity outcomes in people with COPD related diagnoses. DATA SYNTHESIS: Since statistical pooling was not possible, the findings were presented in narrative form including tables and figures to aid in data presentation when appropriate. RESULTS: One 8-week randomized controlled trial conducted in 80 COPD patients in the Netherlands showed polyunsaturated fatty acid supplementation significantly improved exercise capacity compared with the control condition [between-group difference in mean peak workload was 9.7 W (2.5-17.0; P = 0.009); and mean duration was 4.3 min (0.6-7.9; P = 0.023)]. One cross-sectional study conducted in 250 COPD patients in Spain found associations of specific dietary omega-3 fatty acids with inflammation were inconsistent. CONCLUSIONS: Limited evidence provides weak support for the use of omega-3 fatty acid supplementation for reducing chronic inflammation and some support for improving functional capacity in COPD patients. There is no consistent evidence showing that low dietary intake of specific omega-3 fatty acids worsens inflammation and/or function. More evidence is required before routinely incorporating this therapy within COPD management plans. PMID- 26134548 TI - Guidance for conducting systematic scoping reviews. AB - Reviews of primary research are becoming more common as evidence-based practice gains recognition as the benchmark for care, and the number of, and access to, primary research sources has grown. One of the newer review types is the 'scoping review'. In general, scoping reviews are commonly used for 'reconnaissance' - to clarify working definitions and conceptual boundaries of a topic or field. Scoping reviews are therefore particularly useful when a body of literature has not yet been comprehensively reviewed, or exhibits a complex or heterogeneous nature not amenable to a more precise systematic review of the evidence. While scoping reviews may be conducted to determine the value and probable scope of a full systematic review, they may also be undertaken as exercises in and of themselves to summarize and disseminate research findings, to identify research gaps, and to make recommendations for the future research. This article briefly introduces the reader to scoping reviews, how they are different to systematic reviews, and why they might be conducted. The methodology and guidance for the conduct of systematic scoping reviews outlined below was developed by members of the Joanna Briggs Institute and members of five Joanna Briggs Collaborating Centres. PMID- 26134549 TI - Location and Influence of Added Block Copolymers on the Droplet Size in Oil-in Oil Emulsions. AB - We have investigated the effect of added polystyrene-b-poly(ethylene oxide) (SO) copolymer on the stability of oil-in-oil (O/O) emulsions containing polystyrene (PS) and poly(ethylene glycol) (PEG) in chloroform (CHCl3) and directly visualized the location of SO in the emulsions by using dye-labeled SO (SO*) with confocal laser scanning microscopy (CLSM). The emulsion formed by PS/PEG/CHCl3 = 14/6/80 (wt %) consisted of a droplet phase of PS in CHCl3 and a continuous phase containing PEG in CHCl3. SO*s with various molecular weights (Mn,SO) and volume fractions of the PS block in SO (fPS) were prepared via living anionic polymerization and subsequent end-esterification. The effect of SO on the droplet size in the emulsions was investigated as a function of both Mn,SO and fPS. Increasing Mn,SO and decreasing fPS were effective at reducing the droplet size down to less than 1 MUm, which is 100 times smaller than in the absence of SO. The location of SO*s in the O/O emulsions was further investigated by CLSM. We found that the location of SO*s changed from the droplet interior to the liquid liquid interface and then to the continuous phase with decreasing fPS. We discuss the possible mechanism in terms of the relation of SO* location to the droplet size. PMID- 26134550 TI - Design, synthesis, pharmacological evaluation and molecular dynamics of beta amino acids morphan-derivatives as novel ligands for opioid receptors. AB - Structure-Activity Relationship (SAR) is a current approach in the design of new pharmacological agents. We previously reported the synthesis of a novel analogue of morphine, a 2-azabicyclo[3.3.1]nonane, which contains a beta-amino acid. This bicyclic core exhibits two distinctive chemical handles for further elaboration, which allowed us to create a library of morphan-containing compounds by in silico molecular docking on the MU opioid receptor. Lead candidates were synthesized and biological tests were performed to evaluate their ability to bind to opioid receptors. The four top compounds, three phenyl esters and an N-phenylethyl morphan derivative, were selected for Molecular Dynamics simulations to get topological and thermodynamic information. Aromatic morphan derivatives displayed an interacting domain which fits into a hydrophobic cleft and the effect of the substituents in their affinity was explained by the differences in the calculated binding free energies. Our results indicate that the 3D arrangement of the aromatic ring in the morphine derivatives is not a key issue for a specific ligand - MU receptor interaction. Thus, these morphan derivatives represent a new class of opioid receptor ligands which may be of great use in the clinical practice. PMID- 26134551 TI - Novel benzidine and diaminofluorene prolinamide derivatives as potent hepatitis C virus NS5A inhibitors. AB - Our study describes the discovery of a series of highly potent hepatitis C virus (HCV) NS5A inhibitors based on symmetrical prolinamide derivatives of benzidine and diaminofluorene. Through modification of benzidine, l-proline, and diaminofluorene derivatives, we developed novel inhibitor structures, which allowed us to establish a library of potent HCV NS5A inhibitors. After optimizing the benzidine prolinamide backbone, we identified inhibitors embedding meta substituted benzidine core structures that exhibited the most potent anti-HCV activities. Furthermore, through a battery of studies including hERG ligand binding assay, CYP450 binding assay, rat plasma stability test, human liver microsomal stability test, and pharmacokinetic studies, the identified compounds 24, 26, 27, 42, and 43 are found to be nontoxic, and are expected to be effective therapeutic anti-HCV agents. PMID- 26134552 TI - Synthesis and evaluation of novel pleuromutilin derivatives with a substituted pyrimidine moiety. AB - A series of novel pleuromutilin derivatives possessing 6-hydroxy pyrimidine moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the synthesized derivatives against methicillin resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), Bacillus subtilis (B. subtilis), and Escherichia coli (E. coli) were tested by the agar dilution method. The majority of the screened compounds displayed potent activities. Compounds 3 and 6a were found to be the most active antibacterial agents against MRSA and MRSE. Moreover, in the vivo experiment, compound 6a showed comparable antibacterial activity to that of tiamulin, with ED50 of 5.47 mg/kg body weight against MRSA. PMID- 26134553 TI - Epidemiology, Clinical Presentation, and Outcomes of Kawasaki Disease Among Hospitalized Children in an Inner City Hospital Before and After Publication of the American Academy of Pediatrics/American Heart Association Guidelines for Treatment of Kawasaki Disease: An 11-Year Period. AB - The effect of 2004 Kawasaki disease (KD) guidelines on diagnosis and outcome of KD is lacking. We studied the epidemiology of KD in our region and compared the incidence, presentation, and outcome of KD before and after publication of the guidelines. A retrospective chart review was conducted for patients admitted with a diagnosis of KD. Demographics, laboratory data, and clinical data were collected. Comparison was made between 2 groups: prepublication (2000-2004) and postpublication (2005-2009) of guidelines. A total of 312 children were included; 64% were African American, 23% White, and 2% Asian; 61% were boys; 79% were complete KD, and 66% were in winter/spring. There was a significant increase in KD cases over the 11 years. There was no significant difference in clinical findings and outcome between the 2 groups. KD admissions in our region significantly increased during the postpublication period. There was no difference in clinical presentation, laboratory findings, or outcome between the 2 groups. PMID- 26134554 TI - Comparison of Different Screening Methods for Hypertension in Han Adolescents. AB - The aim of this study was to compare different methods of screening for hypertension in Han adolescents. We analyzed data on 3136 Han adolescents (1601 boys and 1535 girls) aged 13 to 17 years from the adolescents hypertension survey of Qinhuangdao in 2006. The blood pressure was classified as without hypertension and with hypertension, consistent with the 2004 Working Group on High Blood Pressure in Children and Adolescents guidelines and the selected screening methods. Sensitivity and specificity were then calculated according to gender range. Somu's formulas and the table proposed by Chiolero had low sensitivities (58.4% to 83.1%), despite good specificities (99.0% to 100.0%). The tables proposed by Mitchell and Kaelber had high sensitivities (100%), but their specificities were low (62.0% to 73.8%). Blood pressure-to-height ratio (BPHR) was a good compromise between sensitivities (boys 99.1% and girls 98.9%) and specificities (boys 91.0% and girls 94.9%). As screening tools, the table proposed by Mitchell and Kaelber and BPHR have high sensitivities. However, BPHR demonstrated specific advantages, and it does not require tables. PMID- 26134555 TI - A novel and versatile nanomachine for ultrasensitive and specific detection of microRNAs based on molecular beacon initiated strand displacement amplification coupled with catalytic hairpin assembly with DNAzyme formation. AB - MicroRNAs are small regulatory molecules that can be used as potential biomarkers of clinical diagnosis, and efforts have been directed towards the development of a simple, rapid, and sequence-selective analysis of microRNAs. Here, we report a simple and versatile colorimetric strategy for ultrasensitive and specific determination of microRNAs based on molecular beacon initiated strand displacement amplification (SDA) and catalytic hairpin assembly (CHA) with DNAzyme formation. The presence of target microRNAs triggers strand displacement amplification to release nicking DNA triggers, which initiate CHA to produce large amounts of CHA products. Meanwhile, the numerous CHA products can combine with hemin to form G-quadruplex/hemin DNAzyme, a well-known horseradish peroxidase (HRP) mimic, catalyzing a colorimetric reaction. Moreover, the purification of the SDA mixture has been developed for eliminating matrix interference to decrease nonspecific CHA products. Under the optimal conditions and using the promising amplification strategy, the established colorimetric nanomachine (biosensor) shows high sensitivity and selectivity in a dynamic response range from 5 fM to 5 nM with a detection limit as low as 1.7 fM (S/N = 3). In addition, a versatile colorimetric biosensor has been developed for detection of different miRNAs by only changing the miRNA-recognition domain of molecular beacon. Thus, this colorimetric biosensor may become a potential alternative tool for biomedical research and clinical molecular diagnostics. PMID- 26134557 TI - Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture. AB - Our laboratory has demonstrated that bone morphogenetic protein 13 prevented the effects of annular injury in an ovine model, maintaining intervertebral disc height, cell numbers and increasing extracellular matrix production compared to degenerated controls. The present study sought to examine the molecular effects of bone morphogenetic protein 13 on human degenerated disc cells and localize its expression in both human degenerate and scoliotic disc tissue. Effect of bone morphogenetic protein 13 on human derived nucleus pulposus, annulus fibrosus and endplate cells cultured in alginate beads was evaluated by changes in proteoglycan and collagen content. Migratory potential of disc cells towards bone morphogenetic protein 13 was also examined. Bone morphogenetic protein 13 induced significant proteoglycan accumulation in nucleus (18%), annulus (21%) and endplate (23%) cells cultured in alginate beads (p<0.05) compared to controls. Further bone morphogenetic protein 13 increased collagen I and II protein expression in nucleus and endplate cells. Nucleus cells displayed a significant chemotactic response towards bone morphogenetic protein 13. The endogenous expression of bone morphogenetic protein 13 in degenerate disc tissue was not different to scoliotic disc. Bone morphogenetic protein 13 has the potential to enhance extracellular matrix accumulation and induce cell migration in certain disc cells. PMID- 26134556 TI - Lung function and exhaled nitric oxide in healthy unsedated African infants. AB - BACKGROUND AND OBJECTIVE: Population-appropriate lung function reference data are essential to accurately identify respiratory disease and measure response to interventions. There are currently no reference data in African infants. The aim was to describe normal lung function in healthy African infants. METHODS: Lung function was performed on healthy South African infants enrolled in a birth cohort study, the Drakenstein child health study. Infants were excluded if they were born preterm or had a history of neonatal respiratory distress or prior respiratory tract infection. Measurements, made during natural sleep, included the forced oscillation technique, tidal breathing, exhaled nitric oxide and multiple breath washout measures. RESULTS: Three hundred sixty-three infants were tested. Acceptable and repeatable measurements were obtained in 356 (98%) and 352 (97%) infants for tidal breathing analysis and exhaled nitric oxide outcomes, 345 (95%) infants for multiple breath washout and 293 of the 333 (88%) infants for the forced oscillation technique. Age, sex and weight-for-age z score were significantly associated with lung function measures. CONCLUSIONS: This study provides reference data for unsedated infant lung function in African infants and highlights the importance of using population-specific data. PMID- 26134558 TI - Diagnostic value of fine needle aspiration and core needle biopsy in special types of breast cancer. AB - BACKGROUND: Although fine needle aspiration (FNA) biopsy is an established tool to assess breast lesions, there has been a trend toward using core needle biopsy (CNB) instead. The aim of this study was to compare the diagnostic accuracy of FNA and CNB in special types of breast cancer. METHODS: A retrospective review of diagnostic results of pre-operatively performed FNA or CNB, or a combination of the two, was conducted. The cases include histologically proven invasive ductal carcinoma of no special type (NST n = 159), invasive lobular carcinoma (ILC n = 65), mucinous carcinoma (MUC n = 51), and apocrine carcinoma (APO n = 25). RESULTS: The absolute diagnostic sensitivity of FNA to detect malignancy in ILC and APO patients was inferior to that of NST patients (p < 0.001 for ILC and APO). Within each cancer type, the sensitivity of CNB was higher than that of FNA in the ILC and APO patients (p < 0.001 and p < 0.05, respectively). As for NST and MUC patients, FNA and CNB had equivalent sensitivity. The sensitivity of FNA alone significantly improved when combined with CNB in NST, ILC and APO patients (p < 0.05, p < 0.001, and p < 0.05, respectively). CONCLUSIONS: Our results suggest that FNA has less diagnostic accuracy than CNB for ILC and APO; thus, the use of CNB should be encouraged when these types of cancer are clinically suspected or when the initial FNA is inconclusive. PMID- 26134559 TI - Bax/Bak-dependent, Drp1-independent Targeting of X-linked Inhibitor of Apoptosis Protein (XIAP) into Inner Mitochondrial Compartments Counteracts Smac/DIABLO dependent Effector Caspase Activation. AB - Efficient apoptosis requires Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP), which releases death-promoting proteins cytochrome c and Smac to the cytosol, which activate apoptosis and inhibit X-linked inhibitor of apoptosis protein (XIAP) suppression of executioner caspases, respectively. We recently identified that in response to Bcl-2 homology domain 3 (BH3)-only proteins and mitochondrial depolarization, XIAP can permeabilize and enter mitochondria. Consequently, XIAP E3 ligase activity recruits endolysosomes into mitochondria, resulting in Smac degradation. Here, we explored mitochondrial XIAP action within the intrinsic apoptosis signaling pathway. Mechanistically, we demonstrate that mitochondrial XIAP entry requires Bax or Bak and is antagonized by pro-survival Bcl-2 proteins. Moreover, intramitochondrial Smac degradation by XIAP occurs independently of Drp1-regulated cytochrome c release. Importantly, mitochondrial XIAP actions are activated cell-intrinsically by typical apoptosis inducers TNF and staurosporine, and XIAP overexpression reduces the lag time between the administration of an apoptotic stimuli and the onset of mitochondrial permeabilization. To elucidate the role of mitochondrial XIAP action during apoptosis, we integrated our findings within a mathematical model of intrinsic apoptosis signaling. Simulations suggest that moderate increases of XIAP, combined with mitochondrial XIAP preconditioning, would reduce MOMP signaling. To test this scenario, we pre-activated XIAP at mitochondria via mitochondrial depolarization or by artificially targeting XIAP to the intermembrane space. Both approaches resulted in suppression of TNF-mediated caspase activation. Taken together, we propose that XIAP enters mitochondria through a novel mode of mitochondrial permeabilization and through Smac degradation can compete with canonical MOMP to act as an anti-apoptotic tuning mechanism, reducing the mitochondrial contribution to the cellular apoptosis capacity. PMID- 26134560 TI - Monocyte Chemotactic Protein-induced Protein 1 and 4 Form a Complex but Act Independently in Regulation of Interleukin-6 mRNA Degradation. AB - It was recently demonstrated that MCPIP1 is a critical factor that controls inflammation and immune homeostasis; however, the relationship between MCPIP1 and other members of this protein family is largely unknown. Here, we report that MCPIP1 interacts with MCPIP4 to form a protein complex, but acts independently in the regulation of IL-6 mRNA degradation. In an effort to identify MCPIP1 interacting proteins by co-immunoprecipitation (Co-IP) and mass-spec analysis, MCPIP4 was identified as a MCPIP1-interacting protein, which was further confirmed by Co-IP and mammalian two-hybrid assay. Immunofluorescence staining showed that MCPIP4 was co-localized with MCPIP1 in the GW-body, which features GW182 and Argonaute 2. Further studies showed that MCPIP1 and MCPIP4 act independently in regulation of IL-6 mRNA degradation. These results suggest that MCPIP1 and MCPIP4 may additively contribute to control IL-6 production in vivo. PMID- 26134561 TI - Endogenous Ligand for GPR120, Docosahexaenoic Acid, Exerts Benign Metabolic Effects on the Skeletal Muscles via AMP-activated Protein Kinase Pathway. AB - Docosahexaenoic acid (DHA) is an endogenous ligand of G protein-coupled receptor 120 (GPR120). However, the mechanisms underlying DHA action are poorly understood. In this study, DHA stimulated glucose uptake in the skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner. GPR120-mediated increase in intracellular Ca(2+) was critical for DHA-mediated AMPK phosphorylation and glucose uptake. In addition, DHA stimulated GLUT4 translocation AMPK-dependently. Inhibition of AMPK and Ca(2+)/calmodulin dependent protein kinase kinase blocked DHA-induced glucose uptake. DHA and GW9508, a GPR120 agonist, increased GPR120 expression. DHA-mediated glucose uptake was not observed in GPR120 knockdown conditions. DHA increased AMPK phosphorylation, glucose uptake, and intracellular Ca(2+) concentration in primary cultured myoblasts. Taken together, these results indicated that the beneficial metabolic role of DHA was attributed to its ability to regulate glucose via the GPR120-mediated AMPK pathway in the skeletal muscles. PMID- 26134562 TI - Engineered and Native Coenzyme B12-dependent Isovaleryl-CoA/Pivalyl-CoA Mutase. AB - Adenosylcobalamin-dependent isomerases catalyze carbon skeleton rearrangements using radical chemistry. We have recently demonstrated that an isobutyryl-CoA mutase variant, IcmF, a member of this enzyme family that catalyzes the interconversion of isobutyryl-CoA and n-butyryl-CoA also catalyzes the interconversion between isovaleryl-CoA and pivalyl-CoA, albeit with low efficiency and high susceptibility to inactivation. Given the biotechnological potential of the isovaleryl-CoA/pivalyl-CoA mutase (PCM) reaction, we initially attempted to engineer IcmF to be a more proficient PCM by targeting two active site residues predicted based on sequence alignments and crystal structures, to be key to substrate selectivity. Of the eight mutants tested, the F598A mutation was the most robust, resulting in an ~17-fold increase in the catalytic efficiency of the PCM activity and a concomitant ~240-fold decrease in the isobutyryl-CoA mutase activity compared with wild-type IcmF. Hence, mutation of a single residue in IcmF tuned substrate specificity yielding an ~4000-fold increase in the specificity for an unnatural substrate. However, the F598A mutant was even more susceptible to inactivation than wild-type IcmF. To circumvent this limitation, we used bioinformatics analysis to identify an authentic PCM in genomic databases. Cloning and expression of the putative AdoCbl-dependent PCM with an alpha2beta2 heterotetrameric organization similar to that of isobutyryl CoA mutase and a recently characterized archaeal methylmalonyl-CoA mutase, allowed demonstration of its robust PCM activity. To simplify kinetic analysis and handling, a variant PCM-F was generated in which the alphabeta subunits were fused into a single polypeptide via a short 11-amino acid linker. The fusion protein, PCM-F, retained high PCM activity and like PCM, was resistant to inactivation. Neither PCM nor PCM-F displayed detectable isobutyryl-CoA mutase activity, demonstrating that PCM represents a novel 5'-deoxyadenosylcobalamin dependent acyl-CoA mutase. The newly discovered PCM and the derivative PCM-F, have potential applications in bioremediation of pivalic acid found in sludge, in stereospecific synthesis of C5 carboxylic acids and alcohols, and in the production of potential commodity and specialty chemicals. PMID- 26134563 TI - Metal Fluoride Inhibition of a P-type H+ Pump: STABILIZATION OF THE PHOSPHOENZYME INTERMEDIATE CONTRIBUTES TO POST-TRANSLATIONAL PUMP ACTIVATION. AB - The plasma membrane H(+)-ATPase is a P-type ATPase responsible for establishing electrochemical gradients across the plasma membrane in fungi and plants. This essential proton pump exists in two activity states: an autoinhibited basal state with a low turnover rate and a low H(+)/ATP coupling ratio and an activated state in which ATP hydrolysis is tightly coupled to proton transport. Here we characterize metal fluorides as inhibitors of the fungal enzyme in both states. In contrast to findings for other P-type ATPases, inhibition of the plasma membrane H(+)-ATPase by metal fluorides was partly reversible, and the stability of the inhibition varied with the activation state. Thus, the stability of the ATPase inhibitor complex decreased significantly when the pump transitioned from the activated to the basal state, particularly when using beryllium fluoride, which mimics the bound phosphate in the E2P conformational state. Taken together, our results indicate that the phosphate bond of the phosphoenzyme intermediate of H(+)-ATPases is labile in the basal state, which may provide an explanation for the low H(+)/ATP coupling ratio of these pumps in the basal state. PMID- 26134565 TI - Receptor-mediated Endocytosis 8 Utilizes an N-terminal Phosphoinositide-binding Motif to Regulate Endosomal Clathrin Dynamics. AB - Receptor-mediated endocytosis 8 (RME-8) is a DnaJ domain containing protein implicated in translocation of Hsc70 to early endosomes for clathrin removal during retrograde transport. Previously, we have demonstrated that RME-8 associates with early endosomes in a phosphatidylinositol 3-phosphate (PI(3)P) dependent fashion. In this study, we have now identified amino acid determinants required for PI(3)P binding within a region predicted to adopt a pleckstrin homology-like fold in the N terminus of RME-8. The ability of RME-8 to associate with PI(3)P and early endosomes is largely abolished when residues Lys(17), Trp(20), Tyr(24), or Arg(26) are mutated resulting in diffuse cytoplasmic localization of RME-8 while maintaining the ability to interact with Hsc70. We also provide evidence that RME-8 PI(3)P binding regulates early endosomal clathrin dynamics and alters the steady state localization of the cation independent mannose 6-phosphate receptor. Interestingly, RME-8 endosomal association is also regulated by the PI(3)P-binding protein SNX1, a member of the retromer complex. Wild type SNX1 restores endosomal localization of RME-8 W20A, whereas a SNX1 variant deficient in PI(3)P binding disrupts endosomal localization of wild type RME-8. These results further highlight the critical role for PI(3)P in the RME-8-mediated organizational control of various endosomal activities, including retrograde transport. PMID- 26134564 TI - Glutamate Stimulates Local Protein Synthesis in the Axons of Rat Cortical Neurons by Activating alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors and Metabotropic Glutamate Receptors. AB - Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. By analyzing the metabolic incorporation of azidohomoalanine, a methionine analogue, in newly synthesized proteins, we find that glutamate treatments up-regulate protein translation not only in intact rat cortical neurons in culture but also in the axons emitting from cortical neurons before making synapses with target cells. The process by which glutamate stimulates local translation in axons begins with the binding of glutamate to the ionotropic AMPA receptors and metabotropic glutamate receptor 1 and members of group 2 metabotropic glutamate receptors on the plasma membrane. Subsequently, the activated mammalian target of rapamycin (mTOR) signaling pathway and the rise in Ca(2+), resulting from Ca(2+) influxes through calcium-permeable AMPA receptors, voltage-gated Ca(2+) channels, and transient receptor potential canonical channels, in axons stimulate the local translation machinery. For comparison, the enhancement effects of brain-derived neurotrophic factor (BDNF) on the local protein synthesis in cortical axons were also studied. The results indicate that Ca(2+) influxes via transient receptor potential canonical channels and activated the mTOR pathway in axons also mediate BDNF stimulation to local protein synthesis. However, glutamate- and BDNF-induced enhancements of translation in axons exhibit different kinetics. Moreover, Ca(2+) and mTOR signaling appear to play roles carrying different weights, respectively, in transducing glutamate- and BDNF-induced enhancements of axonal translation. Thus, our results indicate that exposure to transient increases of glutamate and more lasting increases of BDNF would stimulate local protein synthesis in migrating axons en route to their targets in the developing brain. PMID- 26134566 TI - Intracellular Bacterial Pathogens Trigger the Formation of U Small Nuclear RNA Bodies (U Bodies) through Metabolic Stress Induction. AB - Invasive bacterial pathogens induce an amino acid starvation (AAS) response in infected host cells that controls host defense in part by promoting autophagy. However, whether AAS has additional significant effects on the host response to intracellular bacteria remains poorly characterized. Here we showed that Shigella, Salmonella, and Listeria interfere with spliceosomal U snRNA maturation in the cytosol. Bacterial infection resulted in the rerouting of U snRNAs and their cytoplasmic escort, the survival motor neuron (SMN) complex, to processing bodies, thus forming U snRNA bodies (U bodies). This process likely contributes to the decline in the cytosolic levels of U snRNAs and of the SMN complex proteins SMN and DDX20 that we observed in infected cells. U body formation was triggered by membrane damage in infected cells and was associated with the induction of metabolic stresses, such as AAS or endoplasmic reticulum stress. Mechanistically, targeting of U snRNAs to U bodies was regulated by translation initiation inhibition and the ATF4/ATF3 pathway, and U bodies rapidly disappeared upon removal of the stress, suggesting that their accumulation represented an adaptive response to metabolic stress. Importantly, this process likely contributed to shape the host response to invasive bacteria because down regulation of DDX20 expression using short hairpin RNA (shRNA) amplified ATF3- and NF-kappaB-dependent signaling. Together, these results identify a critical role for metabolic stress and invasive bacterial pathogens in U body formation and suggest that this process contributes to host defense. PMID- 26134567 TI - Heat Shock Protein 90 Associates with the Per-Arnt-Sim Domain of Heme-free Soluble Guanylate Cyclase: IMplications for Enzyme Maturation. AB - Heat shock protein 90 (hsp90) drives heme insertion into the beta1 subunit of soluble guanylate cyclase (sGC) beta1, which enables it to associate with a partner sGCalpha1 subunit and mature into a nitric oxide (NO)-responsive active form. We utilized fluorescence polarization measurements and hydrogen-deuterium exchange mass spectrometry to define molecular interactions between the specific human isoforms hsp90beta and apo-sGCbeta1. hsp90beta and its isolated M domain, but not its isolated N and C domains, bind with low micromolar affinity to a heme free, truncated version of sGCbeta1 (sGCbeta1(1-359)-H105F). Surprisingly, hsp90beta and its M domain bound to the Per-Arnt-Sim (PAS) domain of apo-sGC beta1(1-359), which lies adjacent to its heme-binding (H-NOX) domain. The interaction specifically involved solvent-exposed regions in the hsp90beta M domain that are largely distinct from sites utilized by other hsp90 clients. The interaction strongly protected two regions of the sGCbeta1 PAS domain and caused local structural relaxation in other regions, including a PAS dimerization interface and a segment in the H-NOX domain. Our results suggest a means by which the hsp90beta interaction could prevent apo-sGCbeta1 from associating with its partner sGCalpha1 subunit while enabling structural changes to assist heme insertion into the H-NOX domain. This mechanism would parallel that in other clients like the aryl hydrocarbon receptor and HIF1alpha, which also interact with hsp90 through their PAS domains to control protein partner and small ligand binding interactions. PMID- 26134568 TI - Staphylococcus aureus PerR Is a Hypersensitive Hydrogen Peroxide Sensor using Iron-mediated Histidine Oxidation. AB - In many Gram-positive bacteria PerR is a major peroxide sensor whose repressor activity is dependent on a bound metal cofactor. The prototype for PerR sensors, the Bacillus subtilis PerRBS protein, represses target genes when bound to either Mn(2+) or Fe(2+) as corepressor, but only the Fe(2+)-bound form responds to H2O2. The orthologous protein in the human pathogen Staphylococcus aureus, PerRSA, plays important roles in H2O2 resistance and virulence. However, PerRSA is reported to only respond to Mn(2+) as corepressor, which suggests that it might rely on a distinct, iron-independent mechanism for H2O2 sensing. Here we demonstrate that PerRSA uses either Fe(2+) or Mn(2+) as corepressor, and that, like PerRBS, the Fe(2+)-bound form of PerRSA senses physiological levels of H2O2 by iron-mediated histidine oxidation. Moreover, we show that PerRSA is poised to sense very low levels of endogenous H2O2, which normally cannot be sensed by B. subtilis PerRBS. This hypersensitivity of PerRSA accounts for the apparent lack of Fe(2+)-dependent repressor activity and consequent Mn(2+)-specific repressor activity under aerobic conditions. We also provide evidence that the activity of PerRSA is directly correlated with virulence, whereas it is inversely correlated with H2O2 resistance, suggesting that PerRSA may be an attractive target for the control of S. aureus pathogenesis. PMID- 26134569 TI - Constraining the Lateral Helix of Respiratory Complex I by Cross-linking Does Not Impair Enzyme Activity or Proton Translocation. AB - Complex I (NADH:ubiquinone oxidoreductase) is a multisubunit, membrane-bound enzyme of the respiratory chain. The energy from NADH oxidation in the peripheral region of the enzyme is used to drive proton translocation across the membrane. One of the integral membrane subunits, nuoL in Escherichia coli, has an unusual lateral helix of ~75 residues that lies parallel to the membrane surface and has been proposed to play a mechanical role as a piston during proton translocation (Efremov, R. G., Baradaran, R., and Sazanov, L. A. (2010) Nature 465, 441-445). To test this hypothesis we have introduced 11 pairs of cysteine residues into Complex I; in each pair one is in the lateral helix, and the other is in a nearby region of subunit N, M, or L. The double mutants were treated with Cu(2+) ions or with bi-functional methanethiosulfonate reagents to catalyze cross-link formation in membrane vesicles. The yields of cross-linked products were typically 50-90%, as judged by immunoblotting, but in no case did the activity of Complex I decrease by >10-20%, as indicated by deamino-NADH oxidase activity or rates of proton translocation. In contrast, several pairs of cysteine residues introduced at other interfaces of N:M and M:L subunits led to significant loss of activity, in particular, in the region of residue Glu-144 of subunit M. The results do not support the hypothesis that the lateral helix of subunit L functions like a piston, but rather, they suggest that conformational changes might be transmitted more directly through the functional residues of the proton translocation apparatus. PMID- 26134570 TI - RGC-32 Deficiency Protects against Hepatic Steatosis by Reducing Lipogenesis. AB - Hepatic steatosis is associated with insulin resistance and metabolic syndrome because of increased hepatic triglyceride content. We have reported previously that deficiency of response gene to complement 32 (RGC-32) prevents high-fat diet (HFD)-induced obesity and insulin resistance in mice. This study was conducted to determine the role of RGC-32 in the regulation of hepatic steatosis. We observed that hepatic RGC-32 was induced dramatically by both HFD challenge and ethanol administration. RGC-32 knockout (RGC32(-/-)) mice were resistant to HFD- and ethanol-induced hepatic steatosis. The hepatic triglyceride content of RGC32(-/-) mice was decreased significantly compared with WT controls even under normal chow conditions. Moreover, RGC-32 deficiency decreased the expression of lipogenesis related genes, sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase, and stearoyl-CoA desaturase 1 (SCD1). RGC-32 deficiency also decreased SCD1 activity, as indicated by decreased desaturase indices of the liver and serum. Mechanistically, insulin and ethanol induced RGC-32 expression through the NF-kappaB signaling pathway, which, in turn, increased SCD1 expression in a SREBP-1c-dependent manner. RGC-32 also promoted SREBP-1c expression through activating liver X receptor. These results demonstrate that RGC-32 contributes to the development of hepatic steatosis by facilitating de novo lipogenesis through activating liver X receptor, leading to the induction of SREBP-1c and its target genes. Therefore, RGC-32 may be a potential novel drug target for the treatment of hepatic steatosis and its related diseases. PMID- 26134571 TI - Structure and Function of the Hypertension Variant A486V of G Protein-coupled Receptor Kinase 4. AB - G-protein-coupled receptor (GPCR) kinases (GRKs) bind to and phosphorylate GPCRs, initiating the process of GPCR desensitization and internalization. GRK4 is implicated in the regulation of blood pressure, and three GRK4 polymorphisms (R65L, A142V, and A486V) are associated with hypertension. Here, we describe the 2.6 A structure of human GRK4alpha A486V crystallized in the presence of 5' adenylyl beta,gamma-imidodiphosphate. The structure of GRK4alpha is similar to other GRKs, although slight differences exist within the RGS homology (RH) bundle subdomain, substrate-binding site, and kinase C-tail. The RH bundle subdomain and kinase C-terminal lobe form a strikingly acidic surface, whereas the kinase N terminal lobe and RH terminal subdomain surfaces are much more basic. In this respect, GRK4alpha is more similar to GRK2 than GRK6. A fully ordered kinase C tail reveals interactions linking the C-tail with important determinants of kinase activity, including the alphaB helix, alphaD helix, and the P-loop. Autophosphorylation of wild-type GRK4alpha is required for full kinase activity, as indicated by a lag in phosphorylation of a peptide from the dopamine D1 receptor without ATP preincubation. In contrast, this lag is not observed in GRK4alpha A486V. Phosphopeptide mapping by mass spectrometry indicates an increased rate of autophosphorylation of a number of residues in GRK4alpha A486V relative to wild-type GRK4alpha, including Ser-485 in the kinase C-tail. PMID- 26134572 TI - The C-terminal Domain (CTD) of Human DNA Glycosylase NEIL1 Is Required for Forming BERosome Repair Complex with DNA Replication Proteins at the Replicating Genome: DOMINANT NEGATIVE FUNCTION OF THE CTD. AB - The human DNA glycosylase NEIL1 was recently demonstrated to initiate prereplicative base excision repair (BER) of oxidized bases in the replicating genome, thus preventing mutagenic replication. A significant fraction of NEIL1 in cells is present in large cellular complexes containing DNA replication and other repair proteins, as shown by gel filtration. However, how the interaction of NEIL1 affects its recruitment to the replication site for prereplicative repair was not investigated. Here, we show that NEIL1 binarily interacts with the proliferating cell nuclear antigen clamp loader replication factor C, DNA polymerase delta, and DNA ligase I in the absence of DNA via its non-conserved C terminal domain (CTD); replication factor C interaction results in ~8-fold stimulation of NEIL1 activity. Disruption of NEIL1 interactions within the BERosome complex, as observed for a NEIL1 deletion mutant (N311) lacking the CTD, not only inhibits complete BER in vitro but also prevents its chromatin association and reduced recruitment at replication foci in S phase cells. This suggests that the interaction of NEIL1 with replication and other BER proteins is required for efficient repair of the replicating genome. Consistently, the CTD polypeptide acts as a dominant negative inhibitor during in vitro repair, and its ectopic expression sensitizes human cells to reactive oxygen species. We conclude that multiple interactions among BER proteins lead to large complexes, which are critical for efficient BER in mammalian cells, and the CTD interaction could be targeted for enhancing drug/radiation sensitivity of tumor cells. PMID- 26134574 TI - Development of a new platform for secretory production of recombinant proteins in Corynebacterium glutamicum. AB - Corynebacterium glutamicum, which has been for long an industrial producer of various L-amino acids, nucleic acids, and vitamins, is now also regarded as a potential host for the secretory production of recombinant proteins. To harness its potential as an industrial platform for recombinant protein production, the development of an efficient secretion system is necessary. Particularly, regarding protein production in large-scale bioreactors, it would be appropriate to develop a secretory expression system that is specialized for high cell density cultivation conditions. Here we isolated a new signal peptide that mediates the efficient secretion of recombinant proteins under high cell density cultivation conditions. The secretome of C. glutamicum ATCC 13032 under high cell density cultivation conditions was initially investigated, and one major protein was identified as a hypothetical protein encoded by cg1514. Novel secretory production systems were then developed using the Cg1514 signal peptide and its own promoter. Efficient protein secretion was demonstrated using three protein models: endoxylanase, alpha-amylase, and camelid antibody fragment (VHH). For large-scale production, fed-batch cultivations were also conducted and high yields were successfully achieved--as high as 1.07 g/L (endoxylanase), 782.6 mg/L (alpha-amylase), and 1.57 g/L (VHH)--in the extracellular medium. From the culture media, all model proteins could be simply purified by one-step column chromatography with high purities and recovery yields. To the best of our knowledge, this is the first report of the development of an efficient secretory expression system by secretome analysis under high cell density cultivation conditions in C. glutamicum. PMID- 26134575 TI - Growth, Oxygen Consumption, and Behavioral Responses of Danio rerio to Variation in Dietary Protein and Lipid Levels. AB - In recent years, there has been increasing interest in the welfare of ornamental fish. Diet can significantly impact the welfare of fish, which can manifest as changes in the fish's physical health and behavior. The zebrafish, Danio rerio, is a popular ornamental species; however, little is known about their nutritional requirements with possible implications for their welfare. Here, we investigated the effect of diets with increasing crude protein (iso-caloric diets) and lipid (iso-nitrogenous diets) on the growth performance, oxygen consumption, and behavior of zebrafish. We found no significant effects of crude protein (32%-75%) or lipid (8%-16%) on the specific growth rate or oxygen consumption of fish fed 5% of their body mass (BM)/day, although the highest crude protein and lipid diet resulted in an increase in condition factor. Furthermore, the crude protein diets did not affect zebrafish behavior when fed a 2% BM ration, once a day. This study has shown that a diet with 32% crude protein and a diet with 8% crude lipid, when fed at a 5% BM ration, were sufficient to meet the growth requirements of our zebrafish. These diets supported the fish's physical health and thus benefited their welfare. PMID- 26134573 TI - Reduced Nuclease Activity of Apurinic/Apyrimidinic Endonuclease (APE1) Variants on Nucleosomes: IDENTIFICATION OF ACCESS RESIDUES. AB - Non-coding apurinic/apyrimidinic (AP) sites are generated at high frequency in genomic DNA via spontaneous hydrolytic, damage-induced or enzyme-mediated base release. AP endonuclease 1 (APE1) is the predominant mammalian enzyme responsible for initiating removal of mutagenic and cytotoxic abasic lesions as part of the base excision repair (BER) pathway. We have examined here the ability of wild type (WT) and a collection of variant/mutant APE1 proteins to cleave at an AP site within a nucleosome core particle. Our studies indicate that, in comparison to the WT protein and other variant/mutant enzymes, the incision activity of the tumor-associated variant R237C and the rare population variant G241R are uniquely hypersensitive to nucleosome complexes in the vicinity of the AP site. This defect appears to stem from an abnormal interaction of R237C and G241R with abasic DNA substrates, but is not simply due to a DNA binding defect, as the site specific APE1 mutant Y128A, which displays markedly reduced AP-DNA complex stability, did not exhibit a similar hypersensitivity to nucleosome structures. Notably, this incision defect of R237C and G241R was observed on a pre-assembled DNA glycosylase.AP-DNA complex as well. Our results suggest that the BER enzyme, APE1, has acquired distinct surface residues that permit efficient processing of AP sites within the context of protein-DNA complexes independent of classic chromatin remodeling mechanisms. PMID- 26134576 TI - Risk Factors for Progression of Degenerative Aortic Valve Disease in the Japanese The Japanese Aortic Stenosis Study (JASS) Prospective Analysis. AB - BACKGROUND: Because of ethnic difference in the risk of degenerative aortic valve disease (DAVD), risk factors should be clarified in each race to establish prophylactic strategies for severe aortic valve stenosis (AS). METHODS AND RESULTS: This study prospectively followed 359 Japanese subjects with DAVD and age >=50 years for 3 years. As both patients with peak aortic transvalvular flow velocity >=2 m/s and <2 m/s were enrolled, subgroup analysis was also conducted. Most patients were under treatment for their comorbidities. The use of warfarin, but none of the traditional risk factors for atherosclerosis, was related to greater reduction in aortic valve area indexed to body surface area (iAVA). In patients with peak aortic transvalvular flow velocity <2 m/s, the use of an angiotensin-receptor blocker (ARB) was associated with less decrease in iAVA. In patients with peak velocity >=2 m/s, changes in iAVA were not related to any baseline characteristics, but peak velocity was less increased under treatment with an angiotensin-converting enzyme inhibitor (ACEI). CONCLUSIONS: In Japanese, the use of warfarin may exacerbate DAVD, and augmented management of atherosclerotic risk factors beyond the recommendations in the current guidelines is unlikely to exert additional benefit. The prescription of ARB for DAVD patients before the development of AS or ACEI after the development of AS may be useful. PMID- 26134577 TI - Role of Cardiac Magnetic Resonance Imaging in the Management and Treatment of Ventricular Tachycardia in Patients With Structural Heart Disease. AB - Treatment for ventricular tachycardia (VT) generally includes 1 or more of the following options: antiarrhythmic therapy, an implantable cardioverter defibrillator and/or catheter ablation. Catheter ablation is performed with an electroanatomic mapping system to define the heart's 3D anatomy, as well as regions of scar. Radiofrequency energy is then applied to areas of abnormal substrate within which are located channels critical to the VT circuit. Cardiac magnetic resonance (CMR) imaging is a non-invasive modality that provides high resolution images of cardiac structure and function. CMR has become a very useful tool for sudden cardiac death risk stratification and to facilitate successful radiofrequency ablation of VT in patients with abnormal cardiac substrate. The role of CMR in the management and treatment of VT in patients with structural heart disease is reviewed. PMID- 26134578 TI - Photochemical Formation of Hydroxylated Polybrominated Diphenyl Ethers (OH-PBDEs) from Polybrominated Diphenyl Ethers (PBDEs) in Aqueous Solution under Simulated Solar Light Irradiation. AB - Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are of great concern due to their higher toxicity compared to PBDEs. However, the abiologic process whereby PBDEs are converted to OH-PBDEs in the aquatic environment is not well understood. To explore the possibility of OH-PBDEs photoformation in natural water, the photohydroxylation of BDE-47 has been investigated in aqueous Fe(III) and/or fulvic acid (FA) solutions and in natural lake water under simulated solar light irradiation. The results showed that 6-OH-BDE-47 and 2'-OH-BDE-68 were generated from BDE-47 under these conditions. Based on the identification of derivatives and reactive radicals, OH-PBDEs formation can be ascribed to an addition reaction of ortho-tetra-BDE radical and hydroxyl radical ((*)OH), with or without a subsequent Smiles rearrangement reaction. Since the ortho-tetra-BDE radical could be readily produced by the photolysis of BDE-47, even in pure water, (*)OH production was considered as critical for the photoformation of OH PBDEs. Thus, it is reasonable to deduce that the photoreactive components (Fe(III), FA) in aqueous solution played an important role through influencing (*)OH generation. Although the yields of OH-PBDEs did not increase regularly with increasing concentration of these photoreactive components in solution, this study suggests a possible abiotic origin of OH-PBDEs formation in the aquatic environment. PMID- 26134579 TI - Regulation of FA and TAG biosynthesis pathway genes in endosperms and embryos of high and low oil content genotypes of Jatropha curcas L. AB - The rising demand for biofuels has raised concerns about selecting alternate and promising renewable energy crops which do not compete with food supply. Jatropha (Jatropha curcas L.), a non-edible energy crop of the family euphorbiaceae, has the potential of providing biodiesel feedstock due to the presence of high proportion of unsaturated fatty acids (75%) in seed oil which is mainly accumulated in endosperm and embryo. The molecular basis of seed oil biosynthesis machinery has been studied in J. curcas, however, what genetic differences contribute to differential oil biosynthesis and accumulation in genotypes varying for oil content is poorly understood. We investigated expression profile of 18 FA and TAG biosynthetic pathway genes in different developmental stages of embryo and endosperm from high (42%) and low (30%) oil content genotypes grown at two geographical locations. Most of the genes showed relatively higher expression in endosperms of high oil content genotype, whereas no significant difference was observed in endosperms versus embryos of low oil content genotype. The promoter regions of key genes from FA and TAG biosynthetic pathways as well as other genes implicated in oil accumulation were analyzed for regulatory elements and transcription factors specific to oil or lipid accumulation in plants such as Dof, CBF (LEC1), SORLIP, GATA and Skn-1_motif etc. Identification of key genes from oil biosynthesis and regulatory elements specific to oil deposition will be useful not only in dissecting the molecular basis of high oil content but also improving seed oil content through transgenic or molecular breeding approaches. PMID- 26134580 TI - Explanation of non-additive effects in mixtures of similar mode of action chemicals. AB - Many models have been developed to predict the combined effect of drugs and chemicals. Most models are classified into two additive models: independent action (IA) and concentration addition (CA). It is generally considered if the modes of action of chemicals are similar then the combined effect obeys CA; however, many empirical studies report nonlinear effects deviating from the predictions by CA. Such deviations are termed synergism and antagonism. Synergism, which leads to a stronger toxicity, requires more careful management, and hence it is important to understand how and which combinations of chemicals lead to synergism. In this paper, three types of chemical reactions are mathematically modeled and the cause of the nonlinear effects among chemicals with similar modes of action was investigated. Our results show that combined effects obey CA only when the modes of action are exactly the same. Contrary to existing knowledge, combined effects are generally nonlinear even if the modes of action of the chemicals are similar. Our results further show that the nonlinear effects vanish out when the chemical concentrations are low, suggesting that the current management procedure of assuming CA is rarely inappropriate because environmental concentrations of chemicals are generally low. PMID- 26134581 TI - Importance of investigating epigenetic alterations for industry and regulators: An appraisal of current efforts by the Health and Environmental Sciences Institute. AB - Recent technological advances have led to rapid progress in the characterization of epigenetic modifications that control gene expression in a generally heritable way, and are likely involved in defining cellular phenotypes, developmental stages and disease status from one generation to the next. On November 18, 2013, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) held a symposium entitled "Advances in Assessing Adverse Epigenetic Effects of Drugs and Chemicals" in Washington, D.C. The goal of the symposium was to identify gaps in knowledge and highlight promising areas of progress that represent opportunities to utilize epigenomic profiling for risk assessment of drugs and chemicals. Epigenomic profiling has the potential to provide mechanistic information in toxicological safety assessments; this is especially relevant for the evaluation of carcinogenic or teratogenic potential and also for drugs that directly target epigenetic modifiers, like DNA methyltransferases or histone modifying enzymes. Furthermore, it can serve as an endpoint or marker for hazard characterization in chemical safety assessment. The assessment of epigenetic effects may also be approached with new model systems that could directly assess transgenerational effects or potentially sensitive stem cell populations. These would enhance the range of safety assessment tools for evaluating xenobiotics that perturb the epigenome. Here we provide a brief synopsis of the symposium, update findings since that time and then highlight potential directions for future collaborative efforts to incorporate epigenetic profiling into risk assessment. PMID- 26134582 TI - Distortions of ethyne when complexed with a cuprous or argentous halide: the rotational spectrum of C2H2CuF. AB - A new molecule C2H2CuF has been synthesized in the gas phase by means of the reaction of laser-ablated metallic copper with a pulse of gas consisting of a dilute mixture of ethyne and sulfur hexafluoride in argon. The ground-state rotational spectrum was detected by two types of Fourier-transform microwave spectroscopy, namely that conducted in a microwave Fabry-Perot cavity and the chirped-pulse broadband technique. The spectroscopic constants of the six isotopologues (12)C2H2(63)Cu(19)F, (12)C2H2(65)Cu(19)F, (13)C2H2(63)Cu(19)F, (13)C2H2(65)Cu(19)F, (12)C2D2(63)Cu(19)F and (12)C2D2(65)Cu(19)F were determined and interpreted to show that the molecule has a planar, T-shaped geometry belonging to the molecular point group C2v, with CuF forming the stem of the T. Quantitative interpretation reveals that the ethyne molecule is distorted when subsumed into the complex in such manner that the C[triple bond, length as m dash]C bond lengthens (by deltar) and the two H atoms cease to be collinear with the C[triple bond, length as m-dash]C internuclear line. The H atoms move symmetrically away from the approaching Cu atom of CuF, to increase each *[triple bond, length as m-dash]C-H angle by deltaA = 14.65(2) degrees , from 180 degrees to 194.65(2) degrees . Ab initio calculations at the explicitly-correlated level of theory CCSD(T)(F12*)/aug-cc-pVTZ lead to good agreement with the experimental geometry. It is shown that similar distortions deltar and deltaA, similarly determined, for four complexes C2H2MX (M = Cu or Ag; X = F, Cl or CCH) are approximately linearly related to the energies De for the dissociation process C2H2MX = C2H2 + MX. PMID- 26134583 TI - Loss of Vascular Distensibility During Exercise Is an Early Hemodynamic Marker of Pulmonary Vascular Disease. AB - BACKGROUND: Exercise can distend the normally compliant, thin-walled pulmonary vessels. Loss of distensibility has been suggested as an early marker of pulmonary vascular remodeling. We hypothesized that in mild pulmonary vascular disease (PVD), a reduction in vascular distensibility during exercise occurs prior to the development of overt resting pulmonary hypertension (PH). METHODS: Distensibility alpha during exercise (percentage change in vessel diameter per mm Hg increase in transmural pressure) was estimated in 90 subjects using a model of the pulmonary circulation and invasive hemodynamic data. Distensible properties in mild PVD without resting PH (PVD-noPH) (n = 33) were compared with control subjects (n = 26) and PVD with overt resting PH (PVD-PH) (n = 31). RESULTS: Resting mean pulmonary artery pressure (mPpa) levels were 14 +/- 4, 20 +/- 3, and 34 +/- 10 mm Hg with corresponding exercise mPpa-cardiac output slopes of 1.5 +/- 0.6, 3.5 +/- 0.9, and 5.7 +/- 3.2 mm Hg/L/min for control subjects and the PVD noPH and PVD-PH groups, respectively. The distensible model produced high accuracy and precision with no mean bias and 95% limits of agreement of -4.5 to 4.5 mm Hg between calculated and measured mPpa. Distensibility alpha was lowest in the PVD-PH group, intermediate in the PVD-noPH group, and highest in control subjects (0.25 +/- 0.14%/mm Hg vs 0.45 +/- 0.24%/mm Hg vs 1.40 +/- 0.45%/mm Hg, P < .0001). Distensibility alpha discriminated PVD-noPH from control subjects with a sensitivity of 88% and a specificity of 100%. The discriminatory performance of alpha was similar for the subgroup of PVD-noPH, with a strictly normal resting mPpa <= 20 mm Hg. CONCLUSIONS: Loss of pulmonary vascular distensibility during exercise occurs prior to resting PH in PVD. The usefulness of alpha as a novel vascular index for the early detection of PVD warrants further validation. PMID- 26134584 TI - Near peer teaching in medical curricula: integrating student teachers in pathology tutorials. AB - INTRODUCTION: Due to increased cognitive and social congruence with their tutees, near peer teachers (NPTs) may be capable of more effectively delivering course material. This study examines NPTs as pathology tutors alongside more traditional teachers (e.g., consultants and registrars) to explore their acceptability, effectiveness, and years of 'distance' between tutors and tutees. METHOD: In total, 240 first- and second-year undergraduate medical students were taught set material in a pathology tutorial setting by NPTs (fourth-year medical students), registrars, or consultants. Learners were then asked to provide feedback using a 15-item, Likert-type scale. RESULTS: On 11 of the 15 items, there were no significant differences in students' median ratings. However, NPTs were perceived to be significantly more approachable than consultants, more aware of learning outcomes, more receptive to student input, and more invested in exam success. Compared with second-year students, first-year students showed a preference towards registrar tutors in terms of perceived gain of knowledge and use of time. In contrast, second-year students showed a preference towards NPTs, who provided more perceived knowledge gain and investment in exam success. No significant differences were found regarding consultant tutors. DISCUSSION: Perhaps due to increased congruence with tutees, NPTs show promise as tutors within medical curricula. This provides advantages not only to tutees, but also to tutors - who may gain vital teaching experience and offer an effective supplement to 'traditional' faculty educators. PMID- 26134585 TI - Accelerometric assessment of different dimensions of natural walking during the first year after stroke: Recovery of amount, distribution, quality and speed of walking. AB - OBJECTIVES: To describe the course of walking behaviour over a period of 1 year after stroke, using accelerometry, and to compare 1-year data with those from a healthy group. DESIGN: One-year follow-up cohort study. SUBJECTS: Twenty-three stroke patients and 20 age-matched healthy subjects. METHODS: Accelerometer assessments were made in the participants' daily environment for 8 h/day during the 1st (T1), 12th (T2) and 48th (T3) weeks after stroke, and at one time-point in healthy subjects. Primary outcomes were: percentage of time walking and upright (amount); mean duration and number of walking periods (distribution); step regularity and gait symmetry (quality); and walking speed. RESULTS: Time walking, time upright, and number of walking bouts increased during T1 and T2 (p < 0.01) and then levelled off (p > 0.30). Mean duration of walking periods showed no significant improvements (p > 0.30) during all phases. Step regularity, gait symmetry and gait speed showed a tendency to increase consistently from T1 to T3. At T3, amount and distribution variables reached the level of the healthy group, but significant differences remained (p < 0.02) in step regularity and gait speed. CONCLUSION: In this cohort, different outcomes of walking behaviour showed different patterns and levels of recovery, which supports the multi-dimensional character of gait. PMID- 26134587 TI - Formation and Reactivity of a Molecular Magnesium Hydride with a Terminal Mg-H Bond. AB - A complex featuring a terminal magnesium hydride bond supported by an NNNN macrocyclic ligand, [Mg{Me3 TACD?Al(iBu)3}H] (3), was formed from its labile Al(iBu)3 adduct. Use of Al(iBu)3 to block the amido nitrogen of the NNNN macrocyclic ligand was essential to prevent aggregation. The structurally characterized compound 3 reacted with BH3 to give the BH4 derivative, whereas Me3 SiC?CH and PhSiH3 led to the corresponding acetylide and silyl derivative under H2 elimination. Pyridine is inserted into the Mg?H bond to give selectively the 1,4-dihydropyridinate. PMID- 26134586 TI - Downregulated expression of LBH mRNA in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. AB - We performed a gene expression study to explore whether expression levels of LBH contribute to the pathogenesis of systemic lupus erythematosus (SLE) and are associated with the genome-wide association study-identified SNP (rs7579944 and rs906868) and the SLE Disease Activity Index (SLEDAI). Fluorescent quantitative reverse transcription polymerase chain reaction was used to examine the expression of LBH mRNA in peripheral blood mononuclear cells (PBMC) from 62 SLE patients and 69 controls. The expression levels of LBH mRNA in patients with SLE were significantly decreased compared with those in normal controls (P < 0.001). No significant differences were found between LBH mRNA expression levels and SLEDAI scores, SNP rs7579944 and rs906868. This study suggests that decreased expression of LBH mRNA may be correlated with the pathogenesis of SLE. PMID- 26134588 TI - Radio Frequency Transistors and Circuits Based on CVD MoS2. AB - We report on the gigahertz radio frequency (RF) performance of chemical vapor deposited (CVD) monolayer MoS2 field-effect transistors (FETs). Initial DC characterizations of fabricated MoS2 FETs yielded current densities exceeding 200 MUA/MUm and maximum transconductance of 38 MUS/MUm. A contact resistance corrected low-field mobility of 55 cm(2)/(V s) was achieved. Radio frequency FETs were fabricated in the ground-signal-ground (GSG) layout, and standard de embedding techniques were applied. Operating at the peak transconductance, we obtain short-circuit current-gain intrinsic cutoff frequency, fT, of 6.7 GHz and maximum intrinsic oscillation frequency, fmax, of 5.3 GHz for a device with a gate length of 250 nm. The MoS2 device afforded an extrinsic voltage gain Av of 6 dB at 100 MHz with voltage amplification until 3 GHz. With the as-measured frequency performance of CVD MoS2, we provide the first demonstration of a common source (CS) amplifier with voltage gain of 14 dB and an active frequency mixer with conversion gain of -15 dB. Our results of gigahertz frequency performance as well as analog circuit operation show that large area CVD MoS2 may be suitable for industrial-scale electronic applications. PMID- 26134589 TI - A Pilot Study of Self-Reported Physical Activity and Eating Habits in Turkish Cancer Patients Under Chemotherapy. AB - As in all individuals, improving the quality of life, balanced nutrition and physical activity habits must be acquired in cancer patients. The purpose of this study was to determine eating habits and physical activity of cancer patients receiving chemotherapy. Sixty-six patients were completed the questionnaire included sociodemographic data, type of cancer, anthropometric measurements (size and body weight), dietary and physical activity habits. Body mass index for each patient was calculated. Data were analyzed using Statistical Package for Social Science software. Patients were ranged from underweight to obese according to their body mass index: 6.1% of patients were classified as underweight. Almost half (48.5%, n = 32) reported to be regularly physical active, and 46.9% (n = 15) thereof reported 30 min brisk walking. More vegetables consumption was the most popular answer with 62.1% (n = 41), whereas vegetables/fruit or vegetables/legume consumption was 22.7% (n = 15). Gender differences in food choice and preferring the taste of food were not seen as statistically significant. In this article, patients with different types of cancer reported their eating habits and physical activity. Disease-related and worse prognostic factors were found. An institutional program should be offered to cancer patients for consulting about nutrition and physical activity. PMID- 26134590 TI - Polypyrrole-Based Implantable Electroactive Pump for Controlled Drug Microinjection. AB - Implantable devices for long-lasting controlled insulin microinjection are of great value to diabetic patients. To address this need, we develop a flexible electroactive pump based on a biocompatible polypyrrole composite film that comprises a polypyrrole matrix and a macromolecular dopant of polycaprolactone block-polytetrahydrofuran-block-polycaprolactone. Using phosphate-buffered saline as the electrolyte, this film demonstrates much higher electroactivity and reproducibility than conventional Cl--doped polypyrrole, making it an excellent actuator for driving an implantable pump. At a driving current density of 1 mA/cm2, the pump demonstrates a consistent output capacity of 10.5 at 0.35 MUL/s over 20 cycles. This work paves the way for the development of an implantable electroactive pump to improve the quality of life of diabetics. PMID- 26134591 TI - Thermodynamic and Biophysical Analysis of the Membrane-Association of a Histidine Rich Peptide with Efficient Antimicrobial and Transfection Activities. AB - LAH4-L1 is a synthetic amphipathic peptide with antimicrobial activity. The sequence of the 23 amino acid peptide was inspired by naturally occurring frog peptides such as PGLa and magainin. LAH4-L1 also facilitates the transport of nucleic acids through the cell membrane. We have investigated the membrane binding properties and energetics of LAH4-L1 at pH 5.5 with physical-chemical methods. CD spectroscopy was employed to quantitate the membrane-induced random coil-to-helix transition of LAH4-L1. Binding isotherms were obtained with CD spectroscopy as a function of the lipid-to-protein ratio for neutral and negatively charged membranes and were analyzed with both the Langmuir multisite adsorption model and the surface partition/Gouy-Chapman model. According to the Langmuir adsorption model each molecule LAH4-L1 binds 4 POPS molecules, independent of the POPS concentration in the membrane. This is supported by the surface partition/Gouy-Chapman model which predicts an electric charge of LAH4-L1 of z = 4. Binding affinity is dominated by electrostatic attraction. The thermodynamics of the binding process was elucidated with isothermal titration calorimetry. The ITC data revealed that the binding process is composed of at least three different reactions, that is, a coil-to-helix transition with an exothermic enthalpy of about -11 kcal/mol and two endothermic processes with enthalpies of ~4 and ~8 kcal/mol, respectively, which partly compensate the exothermic enthalpy of the conformational change. The major endothermic reaction is interpreted as a deprotonation reaction following the insertion of a highly charged cationic peptide into a nonpolar environment. PMID- 26134592 TI - Functionalising the azobenzene motif delivers a light-responsive membrane interactive compound with the potential for photodynamic therapy applications. AB - When adorned with n-octyl chains azobenzene is able to disrupt a variety of calcein-loaded phospholipid liposomes. The levels of lysis observed are dependent both on the lipid headgroup and the conformation of the azobenzene compound. In all cases studied, it has been shown that the cis-conformer is more membrane interactive than the trans-conformer, suggesting that this class of molecule could be optimised for photo-dynamic therapy applications against infectious pathogens. PMID- 26134593 TI - Use of dual-energy computed tomography for the evaluation of calcinosis in patients with systemic sclerosis. AB - We examined the usefulness of dual-energy computed tomography (DECT) in the evaluation of symptomatic systemic sclerosis (SSc)-related calcinosis of the hands. We performed DECT scan of the hands in 16 patients with symptomatic SSc calcinosis to better characterize the calcinosis, their locations within the soft tissues, and exclude monosodium urate (MSU) crystal deposition. We also compared their computed tomography (CT) images to plain radiographs of one hand. Pertinent clinical information from this cohort was collected. Sixteen SSc patients underwent DECT and plain X-ray imaging of the hands. Five of the 16 SSc patients in our cohort had overlap disease, either rheumatoid arthritis (RA) and/or myopathy. Calcinosis symptoms included painful deposits (88 %), soft tissue swelling (66 %), and recurrent infections (44 %) from these deposits. On DECT, calcinosis deposits had the same color and density as the bone and no MSU was found. However, their CT images showed better details of the calcinosis locations in the soft tissues as well as the bone destruction, especially if there was overlying bulky deposits or flexion contractures. These deposits were most commonly found in the subcutaneous fat pads of the fingertips, along tendon and muscle groups, or within the carpal tunnel. DECT did not confirm MSU in our cohort with calcinosis. However, CT imaging was superior to plain radiographs in locating these deposits within the soft tissues and may be a useful tool to study SSc-calcinosis affecting the hands, particularly in the setting of progressive hand deformities. PMID- 26134594 TI - 7.7% Efficient All-Polymer Solar Cells. AB - By controlling the polymer/polymer blend self-organization rate, all-polymer solar cells composed of a high-mobility, crystalline, naphthalene diimide selenophene copolymer acceptor and a benzodithiophene-thieno[3,4-b]thiophene copolymer donor are achieved with a record 7.7% power conversion efficiency and a record short-circuit current density (18.8 mA cm(-2)). PMID- 26134595 TI - Safety considerations with fenofibrate/simvastatin combination. AB - INTRODUCTION: Fenofibrate/simvastatin combination is useful for patients with mixed dyslipidemia. Aim of this review is to critically present the safety aspects of the fenofibrate/simvastatin combination. AREAS COVERED: Current evidence regarding the adverse effects of fenofibrate/simvastatin combination is critically presented based on the results of large randomized controlled trials and other relevant studies. Additionally, clinical pharmacology, drug interactions and the effects of fenofibrate and simvastatin on metabolic variables and cardiovascular risk are briefly described. EXPERT OPINION: Large randomized clinical trials show that the combined administration of fenofibrate with simvastatin is not associated with significantly increased incidence of serious adverse events compared with simvastatin monotherapy. The incidence of rhabdomyolysis is slightly increased with fibrate/statin combination compared with monotherapy but the actual risk is very low. Although fenofibrate increases creatinine and homocysteine serum levels, the incidence of diabetic nephropathy and thrombotic events was not significantly increased with fenofibrate/simvastatin combination compared with simvastatin monotherapy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. Furthermore, a decrease in albuminuria was observed with fenofibrate in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and ACCORD Lipid trials. Overall, the combined administration of fenofibrate with simvastatin appears to be safe, unless clinicians give fenofibrate/simvastatin combination to patients with predisposing risk factors for the occurrence of adverse events. PMID- 26134596 TI - Preclinical Validation of Multilevel Intraparenchymal Stem Cell Therapy in the Porcine Spinal Cord. AB - BACKGROUND: Although multiple clinical trials are currently testing different stem cell therapies as treatment alternatives for many neurodegenerative diseases and spinal cord injury, the optimal injection parameters have not yet been defined. OBJECTIVE: To test the spinal cord's tolerance to increasing volumes and numbers of stem cell injections in the pig. METHODS: Twenty-seven female Gottingen minipigs received human neural progenitor cell injections using a stereotactic platform device. Cell transplantation in groups 1 to 5 (5-7 pigs in each) was undertaken with the intent of assessing the safety of an injection volume escalation (10, 25, and 50 uL) and an injection number escalation (20, 30, and 40 injections). Motor function and general morbidity were assessed for 21 days. Full necropsy was performed; spinal cords were analyzed for graft survival and microscopic tissue damage. RESULTS: No mortality or permanent surgical complications were observed during the 21-day study period. All animals returned to preoperative baseline within 14 days, showing complete motor function recovery. The histological analysis showed that there was no significant decrease in neuronal density between groups, and cell engraftment ranged from 12% to 31% depending on the injection paradigm. However, tissue damage was identified when injecting large volumes into the spinal cord (50 MUL). CONCLUSION: This series supports the functional safety of various injection volumes and numbers in the spinal cord and gives critical insight into important safety thresholds. These results are relevant to all translational programs delivering cell therapeutics to the spinal cord. PMID- 26134598 TI - Isofuranodiene is the main volatile constituent of Smyrnium perfoliatum L. subsp. perfoliatum growing in central Italy. AB - The essential oil hydrodistilled from the aerial parts of Smyrnium perfoliatum subsp. perfoliatum growing in central Italy was analysed by GC-MS. The main peak in the gas chromatogram was given by the furanosesquiterpene curzerene which is the Cope rearrangement product of isofuranodiene formed into injector and column during the gas chromatographic run. A truthful quantification of these compounds was achieved by HPLC-DAD analysis which showed that isofuranodiene is the main volatile component (180.0 mg/g eo) of S. perfoliatum subsp. perfoliatum, while curzerene occurs in small amounts (18.1 mg/g eo). PMID- 26134597 TI - Paradoxical Increase in Mortality and Rupture of Intracranial Aneurysms in Microsomal Prostaglandin E2 Synthase Type 1-Deficient Mice: Attenuation by Aspirin. AB - BACKGROUND: Inflammation plays an important role in formation and rupture of intracranial aneurysms. Expression of microsomal prostaglandin E2 (PGE2) synthase type 1 (mPGES-1) is increased in the wall of intracranial aneurysms in humans. PGE2, a by-product of mPGES-1, is associated with inflammation and cerebrovascular dysfunction. OBJECTIVE: To test the hypothesis that deletion of mPGES-1 decreases the formation and rupture of intracranial aneurysms in a murine model. METHODS: Intracranial aneurysms were induced in wild-type and mPGES-1 knockout (mPGES-1 KO) mice by using a combination of deoxycorticosterone acetate salt-induced hypertension and intracranial injection of elastase in the basal cistern. Prevalence of aneurysms, subarachnoid hemorrhage, and mortality were assessed. We also tested the effects of administration of aspirin (6 mg/kg/d) by gavage and PGE2 (1 mg/kg/d) by subcutaneous infusion. RESULTS: Systolic blood pressure and prevalence of aneurysm were similar in wild-type and mPGES-1 KO mice. However, mortality and the prevalence of subarachnoid hemorrhage were markedly increased in mPGES-1 KO mice (P < .05). Bone marrow reconstitution studies suggest that mPGES-1 derived from leukocytes does not appear to increase rupture of intracranial aneurysms. Aspirin, but not PGE2, attenuated the increased mortality in mPGES-1 KO mice (P < .05). CONCLUSION: Vascular mPGES-1 plays a protective role in blood vessels and attenuates rupture of cerebral aneurysms. In contrast to effects on abdominal aneurysms, mPGES-1 deficiency is associated with an increase in rupture of cerebral aneurysms and mortality, which are attenuated by low-dose aspirin. PMID- 26134599 TI - "Delayed Villous Maturation" in Placental Reporting: Concordance amongst Consultant Paediatric Pathologists at a Single Specialist Centre. AB - OBJECTIVE: Delayed villous maturation (DVM) has been associated with an increased risk of adverse pregnancy outcome, including stillbirth, in the late third trimester, but there are limited published data. Moreover, it is recognised that the assessment of villous maturation is subjective and hampered by both intra- and interobserver variability. This audit aims to assess concordance in the reporting of DVM among paediatric pathologists at a single specialist centre in order to improve reproducibility of this potentially important diagnosis. METHODS: A retrospective review of singleton placentas from pregnancies at 35 weeks gestation or above submitted for histopathological examination between June December 2013. Placental slides were reviewed independently by all four paediatric pathologists,, blinded to the original report apart from gestational age; villous maturation was assessed as appropriate, accelerated or delayed for the stated gestational age. RESULTS: A total of 464 placental histopathology reports were reviewed, of which 164 were more than 35 weeks gestation; of these, 42 (26%) were originally reported as DVM. Following the audit slide review, a total of 38 cases (23%) were assessed to show DVM by at least one pathologist. Consensus, with at least three pathologists agreeing to a diagnosis of DVM, was achieved in only 14 cases (9% of all cases reviewed; 37% of all cases called DVM). However, the proportion of overall agreement between two of the pathologists was 0.92. CONCLUSION: Concordance for DVM is poor amongst pathologists and subject to much interobserver variability. Consistency may be improved with stringent application of the diagnostic criteria. PMID- 26134600 TI - Exploring the Factor Structure of a Recovery Assessment Measure among Substance Abusing Youth. AB - To date, the measurement of recovery in the field of substance abuse is limited. Youth recovery from substance abuse is an important area to consider, given the complexities of such issues. The Recovery Assessment Scale (RAS) has been validated with mental health patient populations; however, its measurement characteristics have not been examined for individuals in substance abuse treatment. The current study explored the factor structure of the RAS with a sample of 80 substance-abusing youth who participated in a pilot aftercare study (Mage 20.5, SD=3.5; 71.3% male). Reliability analysis showed an internal consistency of alpha=.90 for the entire RAS measure among the youth sample. Results of exploratory factor analysis identified the following four factors: personal determination, skills for recovery, self-control in recovery, and social support/moving beyond recovery among the substance-abusing youth sample. The RAS also demonstrated sound convergent and divergent validity in comparison to other validated measures of functioning, sobriety, and well-being. Collectively, results support that the RAS has adequate psychometric properties for measuring recovery among substance-abusing youth. PMID- 26134601 TI - Are head bandages really required after middle-ear surgery? A systematic review. AB - OBJECTIVE: A systematic review was performed to evaluate the role and effectiveness of head bandages after routine elective middle-ear surgery. METHODS: Studies that compared the effectiveness of head bandage use after elective middle-ear surgery (e.g. myringoplasty, mastoidectomy and cochlear implantation) were identified using the following databases: Ovid Medline and Embase, the Ebsco collections, the Cochrane Library, PubMed, and Google Scholar. An initial search identified 71 articles. All titles and abstracts were reviewed. Thirteen relevant articles were inspected in more detail; of these, only five met the inclusion criteria. These included three randomised, controlled trials, one retrospective case series and one literature review. RESULTS: The three randomised, controlled trials (level of evidence 1b) showed no statistically significant differences in post-operative outcomes (in terms of complications) associated with head bandage use in middle-ear surgery. This finding was supported by the retrospective case series involving patients undergoing cochlear implantation. CONCLUSION: Current available evidence shows no advantage of head bandage use after middle-ear surgery. Head bandages may not be required after routine, uncomplicated middle-ear surgery. PMID- 26134603 TI - Scaling the CRAG to smooth the path to publication in JSAP. PMID- 26134602 TI - Tanshinone IIA enhances bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in nuclei and mitochondria. AB - Heterologous expression of the Drosophila melanogaster multi-substrate deoxyribonucleoside kinase (Dm-dNK) increases the sensitivity of cancer cells to several cytotoxic nucleoside analogs. Thus, it may be used as a suicide gene in combined gene/chemotherapy treatment of cancer. To further characterize this potential suicide gene, we constructed two retroviral vectors that enabled the expression of Dm-dNK in cancer cells. One vector harbored the wild-type enzyme that localized to the nucleus. The other vector harbored a mitochondrial localized mutant enzyme that was constructed by deleting the nuclear localization signal and fusing it to a mitochondrial import signal of cytochrome c oxidase. A thymidine kinase-deficient osteosarcoma cell line was transduced with the recombinant viruses. The sensitivity and bystander cell killing in the presence of pyrimidine nucleoside analogs (E)-5-(2-bromovinyl)-2'-deoxyuridine and 1-beta D-arabinofuranosylthymine were investigated. Tanshinone IIA is a constituent of Danshen; a traditional Chinese medicine used in the treatment of cardiovascular diseases. This study also looked at the influence of Tanshinone IIA on the bystander effect and the underlying mechanisms. We showed that sensitivity of the osteosarcoma cell line to the nucleoside analogs and the efficiency of bystander cell killing were independent of the subcellular localization of Dm-dNK. The enhanced effect of tanshinone IIA on the bystander effect was related to the increased expression of Cx43 and Cx26. PMID- 26134604 TI - Seeking enrolment for a new treatment for canine osteosarcoma. PMID- 26134606 TI - Foreword. PMID- 26134605 TI - Bubbles in the Pericardium. AB - BACKGROUND: Purulent pericarditis is a rare but life-threatening illness. Often, it may be masked by the primary infectious etiology like pneumonia, endocarditis, or CNS infection, leading to a delay in diagnosis and treatment. Echocardiography is the modality of choice for estimating the presence and size of pericardial effusion and detecting presence of tamponade. CASE REPORT: We present a case of a young man with acute respiratory illness in whom clinical exam, electrocardiography, and classic echocardiographic findings played a key role in diagnosis. An echo-dense effusion (rather than echo-free space) appearing like "bubbles" within the pericardial space was seen and a purulent nature of the fluid was strongly suspected. Prompt institution of antimicrobial therapy and timely pericardial drainage resulted in complete clinical recovery of the patient. CONCLUSIONS: In this case, timely diagnosis and prompt treatment of effusion with pericardial drainage and antibiotics resulted in complete recovery from this otherwise devastating infection. PMID- 26134607 TI - Clinical Efficacy of Endoscopic Submucosal Dissection for Adenocarcinomas of the Esophagogastric Junction. AB - Background and Study Aims There are a few reports about the efficacy of endoscopic submucosal dissection (ESD) for adenocarcinomas of the esophagogastric junction (EGJ). However, there is no detailed analysis that divides EGJ cancers into Barrett's adenocarcinoma and gastric cardia adenocarcinoma. The aim of this study was to analyze the efficacy of ESD for EGJ cancers, comparing these two adenocarcinomas. Patients and Methods This study included 43 patients who underwent ESD for type II EGJ cancers between 2004 and 2011. Pathological examination of resected specimens confirmed 14 cases of Barrett's adenocarcinoma and 29 cases of gastric cardia adenocarcinoma. Cutting margins on the oral side were placed 1 cm from the squamocolumnar junction, or 1 cm away from the slight elevation that is an endoscopic sign of subsquamous carcinoma extension. Clinical outcomes, prevalence and length of subsquamous carcinoma extension, and long-term outcomes were compared between these two types of adenocarcinoma. Results No significant differences in clinical outcomes were found between these two types of adenocarcinoma (en bloc, 100 % versus 100 %; complete, 100 % versus 89.7 %; curative, 85.7 % versus 75.9 %). No serious adverse events were encountered. The prevalence of subsquamous carcinoma extension was significantly higher in Barrett's adenocarcinoma compared with gastric cardia adenocarcinoma. Local and distant recurrence were not observed in any cases with curative resection during the follow-up period (1.6 - 87.6 months). Conclusion ESD for EGJ cancers, including both Barrett's adenocarcinoma and gastric cardia adenocarcinoma, was efficient and useful. ESD with a 1 cm safety margin may be acceptable for EGJ cancers. PMID- 26134608 TI - Endoscopy and the Risk of Venous Thromboembolism: A Case-Control Study. AB - Background and Study Aims To assess whether there was an association between endoscopy and the risk of venous thromboembolism (VTE). Patients and Methods Retrospective case - control study of patients diagnosed with VTE over a 3-year period. Each was age- and sex-matched to one of three controls who attended an outpatient appointment on the same date as that of the diagnosis of VTE in the patients. Patients who had undergone endoscopy within 90 days of VTE were included. On a second analysis, patients who were hospitalized and those with inflammatory bowel disease or malignancy were excluded. The difference in occurrence of endoscopy between cases and controls was examined using the McNemar test. The risk of VTE occurring following endoscopy was quantified by means of odds ratios. Results Forty-five of 436 patients (10.3 %) had undergone an endoscopy in the VTE group compared with 14 /436 controls (3.2 %; P < 0.001). The odds ratio for developing a VTE after an endoscopic procedure was 3.58 (95 % CI 1.86 - 7.46) for patients relative to controls. When the 10 hospitalized patients and respective controls were excluded, the odds of VTE remained nearly 3 times as large for patients undergoing endoscopy as for controls (2.92 [95 % CI 1.51, 5.62]; P = 0.001). When patients with inflammatory bowel disease or malignancy were also excluded, no difference was found between patients undergoing endoscopy and controls (1.92 [0.95, 3.85]; P = 0.07). Ten percent of patients with VTE underwent endoscopy in the 3 months before the diagnosis compared with 3 % of controls (P < 0.001). No significant difference was found between the type of endoscopy performed and VTE risk. Conclusions When those with known risk factors for VTE were excluded, no significant increased risk of VTE was found. PMID- 26134609 TI - Duodenal-jejunal bypass liner implantation provokes rapid weight loss and improved glycemic control, accompanied by elevated fasting ghrelin levels. AB - BACKGROUND AND STUDY AIMS: Endoscopic implantation of a duodenal-jejunal bypass liner (DJBL) is a novel bariatric technique to induce weight loss and remission of type 2 diabetes mellitus. Placement of the DJBL mimics the bypass component of the Roux-en-Y gastric bypass (RYGB) procedure. In this observational study, we evaluated improvement of glycemic control and weight loss in the course of the treatment (0 - 24 weeks after DJBL implantation) and analyzed accompanying gut hormone responses. PATIENTS AND METHODS: 12 obese individuals with type 2 diabetes were selected for DJBL implantation. Body weight, fat mass, and fasting plasma levels of glucose, insulin, C-peptide, and glycated hemoglobin (HbA1c), were analyzed at 0, 1, 4 and 24 weeks post-implant. Fasting ghrelin, gastric inhibitory peptide (GIP), and glucagon-like peptide (GLP-1) were determined at 0, 1 and 4 weeks post-implant. RESULTS: Besides significant weight loss, fat mass, fasting insulin, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index were also significantly decreased after DJBL implantation and a 42 % reduction was found in diabetes medication (P < 0.05). The fasting GLP-1 response in the first 4 weeks post-implant was significantly correlated with the fasting insulin and HOMA-IR response. Fasting ghrelin was found to be significantly elevated, in contrast to the decrease in ghrelin that is found after RYGB surgery. CONCLUSIONS: DJBL implantation provoked significant weight loss, a decrease in fat mass, and an early remission of type 2 diabetes, comparable to results seen after RYGB surgery. Gut hormone analyses revealed a potential role of fasting GLP-1 in early remission of type 2 diabetes. Interestingly, the DJBL-induced elevation of ghrelin contradicts the suggested role of reduced ghrelin levels after RYGB in improvement of glycemic control. PMID- 26134611 TI - Over-the-scope clip placement is effective rescue therapy for severe acute upper gastrointestinal bleeding. AB - BACKGROUND AND STUDY AIM: The novel over-the-scope clip (OTSC) allows for excellent apposition of tissue, potentially permitting hemostasis to be achieved in various types of gastrointestinal lesions. This study aimed to evaluate the usefulness and safety of OTSCs for endoscopic hemostasis in patients with upper gastrointestinal bleeding in whom traditional endoscopic methods had failed. PATIENTS AND METHODS: A retrospective case series of all patients who underwent placement of an OTSC for severe recurrent upper gastrointestinal bleeding over a 14-month period was studied. Outcome data for the procedure included achievement of primary hemostasis, episodes of recurrent bleeding, and complications. RESULTS: Twelve consecutive patients (67 % men; mean age 59, range 29 - 86) with ongoing upper gastrointestinal bleeding despite previous endoscopic management were included. They had a mean ASA score of 3 (range 2 - 4), a mean hemoglobin of 7.2 g/dL (range 5.2 - 9.1), and shock was present in 75 % of patients. They had all received packed red blood cells (mean 5.1 units, range 2 - 12). The etiology of bleeding was: duodenal ulcer (n = 6), gastric ulcer (n = 2) Dieulafoy lesion (n = 2), anastomotic ulceration (n = 1), Mallory - Weiss tear (n = 1). Hemostasis was achieved in all patients. Rebleeding occurred in two patients 1 day and 7 days after OTSC placement. There were no complications associated with OTSC application. CONCLUSIONS: OTSC use represents an effective, easily performed, and safe endoscopic therapy for various causes of severe acute gastrointestinal bleeding when conventional endoscopic techniques have failed. This therapy should be added to the armamentarium of therapeutic endoscopists. PMID- 26134610 TI - Adverse events in older patients undergoing ERCP: a systematic review and meta analysis. AB - BACKGROUND AND STUDY AIMS: Biliary and pancreatic diseases are common in the elderly; however, few studies have addressed the occurrence of adverse events in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Our objective was to determine the incidence rates of specific adverse events in this group and calculate incidence rate ratios (IRRs) for selected comparison groups. PATIENTS AND METHODS: Bibliographical searches were conducted in Medline, EMBASE, and Cochrane library databases. The studies included documented the incidence of adverse events (perforation, pancreatitis, bleeding, cholangitis, cardiopulmonary adverse events, mortality) in patients aged >= 65 who underwent ERCP. Pooled incidence rates were calculated for each reported adverse event and IRRs were determined for available comparison groups. A parallel analysis was performed in patients aged >= 80 and >= 90. RESULTS: Our literature search yielded 7429 articles, of which 69 studies met our inclusion criteria. Pooled incidence rates for adverse events (per 1000 ERCPs) in patients aged >= 65 were as follows: perforation 3.8 (95 %CI 1.8 - 7.0), pancreatitis 13.1 (95 %CI 11.0 - 15.5), bleeding 7.7 (95 %CI 5.7 - 10.1), cholangitis 16.1 (95 %CI 11.7 - 21.7), cardiopulmonary events 3.7 (95 %CI 1.5 - 7.6), and death 7.1 (95 %CI 5.2 - 9.4). Patients >= 65 had lower rates of pancreatitis (IRR 0.3, 95 %CI 0.3 - 0.4) compared with younger patients. Octogenarians had higher rates of death (IRR 2.4, 95 %CI 1.3 - 4.5) compared with younger patients, whereas nonagenarians had increased rates of bleeding (IRR 2.4, 95 %CI 1.1 - 5.2), cardiopulmonary events (IRR 3.7, 95 %CI 1.0 - 13.9), and death (IRR 3.8, 95 %CI 1.0 - 14.4). Conclusions ERCP appears to be safe in elderly patients, except in the very elderly who are at higher risk of some adverse events. These data on adverse event rates can help to inform clinical decision-making, the consent process, and comparative effectiveness analyses. PMID- 26134612 TI - The evil lies below the surface: Subsquamous tumor extension in Barrett's adenocarcinoma. PMID- 26134613 TI - ERCP in the elderly: handle with care. PMID- 26134614 TI - Embolization versus surgery for peptic ulcer bleeding after failed endoscopic hemostasis: a meta-analysis. AB - BACKGROUND AND STUDY AIMS: A meta-analysis was conducted to assess the efficacy of transcatheter arterial embolization (TAE) compared with surgery in the management of patients with recurrent nonvariceal upper gastrointestinal bleeding (NVUGIB) after failure of endoscopic hemostasis. PATIENTS AND METHODS: Publications in English and non-English literatures (OVID, MEDLINE, and EMBASE) and abstracts from major international conferences were searched for studies comparing TAE with surgery for treatment of NVUGIB after endoscopic hemostasis failure. Outcome measures included rebleeding rate, all-cause mortality rate, and need for additional interventions to secure hemostasis. RESULTS: From 1234 citations, 6 retrospective comparative studies were included that involved 423 patients (TAE, 182, 56 % male; surgery, 241, 68 % male). TAE patients were older (mean age, TAE 75, surgery, 68). The risk of rebleeding was significantly higher in TAE patients compared with surgically treated patients (relative risk [RR] 1.82, 95 % confidence interval [95 %CI] 1.23 - 2.67), with no statistically significant heterogeneity among the included studies (P = 0.66, I (2) = 0.0 %). After sensitivity analysis excluding studies with a large age difference between the two groups, a higher risk of bleeding remained in the TAE group (RR 2.64, 95 %CI] 1.48 - 4.71). No significant difference in mortality (RR 0.87, 95 %CI 0.59 - 1.29) or requirement for additional interventions (RR 1.67, 95 %CI 0.75 - 3.70) was shown between the two groups. CONCLUSION: A higher rebleeding rate was observed after TAE, suggesting surgery more definitively secured hemostasis, with no significant difference in mortality rate or requirement of additional interventions. The TAE patients were older and in poorer health, thus future randomized studies are needed for accurate comparison of the two modalities. PMID- 26134615 TI - Targeting synthetic Human Papillomavirus (HPV) L2 disulfide-induced N-terminus conformational epitopes for pan-HPV vaccine development. AB - BACKGROUND: Current vaccines against Human Papillomavirus (HPV) are highly effective and based on recombinant virus-like particles (VLPs) of the major capsid protein L1. Since these vaccines are HPV type-specific and expensive for global implementation, an alternative, broader-spectrum immunogen would be the N terminus of the minor capsid protein L2 that induces low titered broadly cross neutralizing antibodies. Here we analyzed the reactivity of different synthetic L2 peptides containing N-terminus amino acids 17-36 in order to test their antigenicity. METHODS: Different synthetic peptides were designed to target the 17-36 amino acid sequences, present in highly antigenic amino-terminus of L2 protein. Six different peptides including Cys22-Cys28 disulfide bonded cyclized L2 peptide were examined for their antigenicity against mouse monoclonal antibody RG-1 and rabbit polyclonal antisera to HPV L2 by enzyme-linked immunosorbent assay (ELISA). RESULTS: Here we report that the cyclized form of synthetic L2 peptide, which is formed through Cys22-Cys28 disulfide bridges, has the highest reactivity to antibodies than other synthetic L2 peptides. CONCLUSION: A cyclized L2 peptide has potential to be an excellent candidate to formulate a low-cost, broadly protective pan-oncogenic HPV vaccine. PMID- 26134616 TI - Predominant contribution of cis-regulatory divergence in the evolution of mouse alternative splicing. AB - Divergence of alternative splicing represents one of the major driving forces to shape phenotypic diversity during evolution. However, the extent to which these divergences could be explained by the evolving cis-regulatory versus trans-acting factors remains unresolved. To globally investigate the relative contributions of the two factors for the first time in mammals, we measured splicing difference between C57BL/6J and SPRET/EiJ mouse strains and allele-specific splicing pattern in their F1 hybrid. Out of 11,818 alternative splicing events expressed in the cultured fibroblast cells, we identified 796 with significant difference between the parental strains. After integrating allele-specific data from F1 hybrid, we demonstrated that these events could be predominately attributed to cis regulatory variants, including those residing at and beyond canonical splicing sites. Contrary to previous observations in Drosophila, such predominant contribution was consistently observed across different types of alternative splicing. Further analysis of liver tissues from the same mouse strains and reanalysis of published datasets on other strains showed similar trends, implying in general the predominant contribution of cis-regulatory changes in the evolution of mouse alternative splicing. PMID- 26134618 TI - Air-gating and chemical-gating in transistors and sensing devices made from hollow TiO2 semiconductor nanotubes. AB - Rapid miniaturization of electronic devices down to the nanoscale, according to Moore's law, has led to some undesirable effects like high leakage current in transistors, which can offset additional benefits from scaling down. Development of three-dimensional transistors, by spatial extension in the third dimension, has allowed higher contact area with a gate electrode and better control over conductivity in the semiconductor channel. However, these devices do not utilize the large surface area and interfaces for new electronic functionality. Here, we demonstrate air gating and chemical gating in hollow semiconductor nanotube devices and highlight the potential for development of novel transistors that can be modulated using channel bias, gate voltage, chemical composition, and concentration. Using chemical gating, we reversibly altered the conductivity of nanoscaled semiconductor nanotubes (10-500 nm TiO2 nanotubes) by six orders of magnitude, with a tunable rectification factor (ON/OFF ratio) ranging from 1 10(6). While demonstrated air- and chemical-gating speeds were slow here (~seconds) due to the mechanical-evacuation rate and size of our chamber, the small nanoscale volume of these hollow semiconductors can enable much higher switching speeds, limited by the rate of adsorption/desorption of molecules at semiconductor interfaces. These chemical-gating effects are completely reversible, additive between different chemical compositions, and can enable semiconductor nanoelectronic devices for 'chemical transistors', 'chemical diodes', and very high-efficiency sensing applications. PMID- 26134617 TI - Significance of filamin A in mTORC2 function in glioblastoma. AB - BACKGROUND: Glioblastoma multiforme (GBM) is one of the most highly metastatic cancers. GBM has been associated with a high level of the mechanistic target of rapamycin complex 2 (mTORC2) activity. We aimed to observe roles of mTORC2 in GBM cells especially on actin cytoskeleton reorganization, cell migration and invasion, and further determine new important players involved in the regulation of these cellular processes. METHODS: To further investigate the significance of mTORC2 in GBM, we treated GBM cells with PP242, an ATP-competitive inhibitor of mTOR, and used RICTOR siRNA to knock down mTORC2 activity. Effects on actin cytoskeleton, focal adhesion, migration, and invasion of GBM cells were examined. To gain insight into molecular basis of the mTORC2 effects on cellular cytoskeletal arrangement and motility/invasion, we affinity purified mTORC2 from GBM cells and identified proteins of interest by mass spectrometry. Characterization of the protein of interest was performed. RESULTS: In addition to the inhibition of mTORC2 activity, we demonstrated significant alteration of actin distribution as revealed by the use of phalloidin staining. Furthermore, vinculin staining was altered which suggests changes in focal adhesion. Inhibition of cell migration and invasion was observed with PP242. Two major proteins that are associated with this mTORC2 multiprotein complex were found. Mass spectrometry identified one of them as Filamin A (FLNA). Association of FLNA with RICTOR but not mTOR was demonstrated. Moreover, in vitro, purified mTORC2 can phosphorylate FLNA likewise its known substrate, AKT. In GBM cells, colocalization of FLNA with RICTOR was observed, and the overall amounts of FLNA protein as well as phosphorylated FLNA are high. Upon treatments of RICTOR siRNA or PP242, phosphorylated FLNA levels at the regulatory residue (Ser2152) decreased. This treatment also disrupted colocalization of Actin filaments and FLNA. CONCLUSIONS: Our results support FLNA as a new downstream effector of mTORC2 controlling GBM cell motility. This new mTORC2-FLNA signaling pathway plays important roles in motility and invasion of glioblastoma cells. PMID- 26134620 TI - The hemodynamic patterns in hypertensive men and women of different age. AB - Aging is associated with cardiovascular remodeling, which can be accelerated in arterial hypertension (AH). The aim of this study was to evaluate the relation between hemodynamic profile and age, as well as to identify the role of sex in hemodynamic patterns of aging in AH. The study comprised 326 patients with AH (mean age: 44.3 years). Two-dimensional echocardiography was performed to evaluate, that is, left ventricular diastolic dysfunction (LVDD) and ejection fraction (LVEF), and ICG to evaluate, that is, acceleration time index (ACI), velocity index (VI), total arterial compliance (TAC), systemic vascular resistance index (SVRI) and thoracic fluid content (TFC). The statistical analysis included interquartile comparison in subgroups of age <19-37 years (Q1), 38-44 years (Q2), 45-51 years (Q3) and 52-68 years (Q4). Aging was associated with: (1) higher prevalence of LVDD (Q1 vs Q4: 11.0% vs 24.7%, P=0.023); (2) altered LV systolic performance-ACI (81.4 vs 64.0 1/100 Omega s(-2), P=0.0001), VI (50.5 vs 42.8 1/1000 Omega s(-1), P=0.006), LVEF (65.4% vs 67.0%, NS); and (3) increased afterload-TAC (2.25 vs 1.87 ml mm Hg(-1), P=0.0001), SVRI (2182 vs 2407 dyn s m(2) cm(-)(5); P=0.045). The 'U-shaped' relation to age was observed for TFC. The above-mentioned hemodynamic trends were more pronounced in men, whereas females presented the 'middle-aged delay'. The influence of aging on cardiovascular system shows in progressive arterial stiffness and impaired left ventricular function. Thoracic fluid reduction may be compensatory to vasoconstriction but its efficiency declines with age. The patterns of cardiovascular aging are different in men and women. PMID- 26134621 TI - Renal sympathetic denervation: effect on ambulatory blood pressure and blood pressure variability in patients with treatment-resistant hypertension. The ReShape CV-risk study. AB - Renal sympathetic denervation (RDN) represents a potential treatment option for highly selected patients with resistant arterial hypertension. In this open label study, we aimed to investigate the response of blood pressure (BP) and short-term BP variability (BPV) to RDN 6 months after procedure. We defined treatment resistant hypertension as office systolic BP>140 mm Hg, despite maximum tolerated doses of ?4 antihypertensive drugs, including a diuretic. In addition, daytime systolic ambulatory blood pressure (ABPM) >135 mm Hg was required after witnessed intake of antihypertensive drugs. Bilateral RDN was performed with the Symplicity Catheter System (n=23). The mean systolic office BP and ABPM fell from 162+/-20 mm Hg to 139+/-19 mm Hg (P<0.001) and from 154+/-20 mm Hg to 144+/-16 mm Hg (P<0.038), respectively. In addition, we observed a significant reduction in diastolic office BP and ABPM. The current study also demonstrated a significant decrease of both systolic and diastolic average real variability, weighted standard deviation (s.d.) as well as conventional s.d. of mean and daytime BP, but not of s.d. of nighttime BP. RDN after witnessed intake of ?4 antihypertensive drugs reduced both office BP and ABPM at 6 months in patients with truly resistant hypertension. Also BPV improved, possibly reflecting an additional effect from intervening on the sympathetic nerve system. PMID- 26134622 TI - Siesta is associated with reduced systolic blood pressure level and decreased prevalence of hypertension in older adults. PMID- 26134623 TI - Cardiac structure and function is related to current blood pressure rather than to previous hypertensive pregnancy. PMID- 26134619 TI - Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging. AB - The development of methods to accurately quantify cell-surface receptors in living tissues would have a seminal impact in oncology. For example, accurate measures of receptor density in vivo could enhance early detection or surgical resection of tumors via protein-based contrast, allowing removal of cancer with high phenotype specificity. Alternatively, accurate receptor expression estimation could be used as a biomarker to guide patient-specific clinical oncology targeting of the same molecular pathway. Unfortunately, conventional molecular contrast-based imaging approaches are not well adapted to accurately estimating the nanomolar-level cell-surface receptor concentrations in tumors, as most images are dominated by nonspecific sources of contrast such as high vascular permeability and lymphatic inhibition. This article reviews approaches for overcoming these limitations based upon tracer kinetic modeling and the use of emerging protocols to estimate binding potential and the related receptor concentration. Methods such as using single time point imaging or a reference tissue approach tend to have low accuracy in tumors, whereas paired-agent methods or advanced kinetic analyses are more promising to eliminate the dominance of interstitial space in the signals. Nuclear medicine and optical molecular imaging are the primary modalities used, as they have the nanomolar level sensitivity needed to quantify cell-surface receptor concentrations present in tissue, although each likely has a different clinical niche. PMID- 26134624 TI - Uric acid blood levels and relationship with the components of metabolic syndrome in hypertensive patients. AB - Associations between high serum uric acid (SUA) levels and high blood pressure (BP), as well as between SUA levels and metabolic syndrome (MetS) have already been reported. The aim of the study was to investigate the relationship between the components of MetS with the SUA levels as also between SUA and apolipoproteins A1 and B (apoA1 and apoB) ratio in hypertensive patients. A total of 2577 consecutive hypertensive patients (1193 male and 1384 female) aged 57.5+/ 13.3 years, were enrolled in our research. Samples were taken to measure SUA, glucose, triglycerides, high density lipoprotein (HDL-C), components of the MetS and apoA1 and apoB. The study population was divided into two groups: group A: SUA levels above normal range (men ?7 mg dl(-1), women ?6 mg dl(-1)) and group B: SUA levels within normal range. In the overall study population, SUA levels showed a statistically significant correlation with waist circumference (WC; r=0.293, P<0.000), triglycerides (r=0.197, P<0.000), glucose (r=0.085, P<0.000), apoB/apoA1 (r=0.136, P<0.000) and HDL-C (r=-0.235, P<0,001). In newly diagnosed untreated hypertensive patients there was also a statistically significant correlation of SUA levels with WC (r=0.331, P<0.001), triglycerides (r=0.228, P<0.001) apoB/apoA1 ratio (r=0.202, P<0.001) and HDL-C (r=-0.278, P<0.001). In hyperurecemic hypertensives there was a statistically significant correlation between SUA levels with WC (r=0.168, P=0.007), apoB/apoA1 ratio (r=0.256, P=0.003) and HDL-C (r=-0.202, P<0.001). SUA levels correlate significantly with all the components of MetS, as well as with the risk factor apoB/apoA1 ratio, in hypertensive patients. PMID- 26134625 TI - Antinociceptive effects of hydroalcoholic extract from Euterpe oleracea Mart. (Acai) in a rodent model of acute and neuropathic pain. AB - BACKGROUND: Plants rich in flavonoids, such as acai (Euterpe oleraceae Mart.), can induce antinociception in experimental animals. Here, we tested an extract obtained from the stones of acai fruits (acai stone extract, ASE), a native plant from the Amazon region of Brazil, in models of acute/inflammatory and chronic pain. METHODS: Antinociceptive effects of ASE were evaluated in the hot plate, formalin, acetic acid writhing, carrageenan, and neuropathic pain models, as well as in thermal hyperalgesia and mechanical allodynia models induced by spinal nerve ligation. Antinociceptive activities were modulated by the administration of cholinergic, adrenergic, opioid, and L-arginine-NO antagonists. RESULTS: Oral administration of ASE (30, 100, or 300 mg.kg(-1)) dose-dependently reduced nociceptive responses to acute/inflammatory pain in mice, including thermal hyperalgesia, acetic acid-induced writhing, and carrageenan-induced thermal hyperalgesia. Moreover, ASE reduced the neurogenic and inflammatory phases after intraplantar injection of formalin in mice. The antinociceptive effect of ASE (100 mg . kg(-1)) in a hot plate protocol, was inhibited by pre-treatment with naloxone (1 mg . kg(-1)), atropine (2 mg . kg(-1)), yohimbine (5 mg . kg(-1)), or L-NAME (30 mg . kg(-1)). Furthermore, ASE prevented chronic pain in a rat spinal nerve ligation model, including thermal hyperalgesia and mechanical allodynia. CONCLUSION: ASE showed significant antinociceptive effect via a multifactorial mechanism of action, indicating that the extract may be useful in the development of new analgesic drugs. PMID- 26134626 TI - Topology adaptive vessel network skeleton extraction with novel medialness measuring function. AB - Vessel tree skeleton extraction is widely applied in vascular structure segmentation, however, conventional approaches often suffer from the adjacent interferences and poor topological adaptability. To avoid these problems, a robust, topology adaptive tree-like structure skeleton extraction framework is proposed in this paper. Specifically, to avoid the adjacent interferences, a local message passing procedure called Gaussian affinity voting (GAV) is proposed to realize adaptive scale-growing of vessel voxels. Then the medialness measuring function (MMF) based on GAV, namely GAV-MMF, is constructed to extract medialness patterns robustly. In order to improve topological adaptability, a level-set graph embedded with GAV-MMF is employed to build initial curve skeletons without any user interaction. Furthermore, the GAV-MMF is embedded in stretching open active contours (SOAC) to drive the initial curves to the expected location, maintaining smoothness and continuity. In addition, to provide an accurate and smooth final skeleton tree topology, topological checks and skeleton network reconfiguration is proposed. The continuity and scalability of this method is validated experimentally on synthetic and clinical images for multi-scale vessels. Experimental results show that the proposed method achieves acceptable topological adaptability for skeleton extraction of vessel trees. PMID- 26134627 TI - Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity in the ?7 SMA Mouse. AB - Spinal muscular atrophy is caused by loss of the SMN1 gene and retention of SMN2. The SMN2 copy number inversely correlates with phenotypic severity and is a modifier of disease outcome. The SMN2 gene essentially differs from SMN1 by a single nucleotide in exon 7 that modulates the incorporation of exon 7 into the final SMN transcript. The majority of the SMN2 transcripts lack exon 7 and this leads to a SMN protein that does not effectively oligomerize and is rapidly degraded. However the SMN2 gene does produce some full-length SMN and the SMN2 copy number along with how much full-length SMN the SMN2 gene makes correlates with severity of the SMA phenotype. However there are a number of discordant SMA siblings that have identical haplotypes and SMN2 copy number yet one has a milder form of SMA. It has been suggested that Plastin3 (PLS3) acts as a sex specific phenotypic modifier where increased expression of PLS3 modifies the SMA phenotype in females. To test the effect of PLS3 overexpression we have over expressed full length PLS3 in SMA mice. To ensure no disruption of functionality or post translational processing of PLS3 we did not place a tag on the protein. PLS3 protein was expressed under the Prion promoter as we have shown previously that SMN expression under this promoter can rescue SMA mice. High levels of PLS3 mRNA were expressed in motor neurons along with an increased level of PLS3 protein in total spinal cord, yet there was no significant beneficial effect on the phenotype of SMA mice. Specifically, neither survival nor the fundamental electrophysiological aspects of the neuromuscular junction were improved upon overexpression of PLS3 in neurons. PMID- 26134628 TI - Motivation to change and perceptions of the admission process with respect to outcome in adolescent anorexia nervosa. AB - BACKGROUND: In patients with anorexia nervosa (AN), there is evidence that readiness to change is an important predictor of outcome with respect to weight gain and improvement in eating disorder psychopathology. In particular, young patients are characterized by a low level of motivation for recovery and perceive more coercion at hospitalization. Thus, a better understanding of the variables that influence readiness to change and perception of the admission process in adolescent AN may help to support patients in initiating change and staying motivated for treatment. METHODS: In 40 adolescent patients diagnosed with AN according to DSM-IV criteria, we assessed in a prospective clinical cohort study the motivation to change using the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ) at admission to inpatient treatment, in week 9 after admission and at discharge. Additional variables were assessed, including depressive symptoms (Beck Depression Inventory, BDI), eating disorder-specific psychopathology (Eating Disorder Inventory, EDI-2), body mass index (BMI) and the percentage of expected body weight (%EBW). The patients' perceptions of the admission process and their perceived need for hospitalization were assessed using a self-report scale developed by Guarda et al. (2007). RESULTS: Younger patients perceived more coercion than older patients did. Low %EBW and more severe eating disorder-specific psychopathology were associated with a greater perceived need for hospitalization. Moreover, low %EBW at admission and a longer duration of illness were accompanied by a greater motivation to change at admission, whereas more severe eating disorder psychopathology was associated with a low motivation to change. The motivation to change increased significantly between admission and discharge. Patients with a greater motivation to change at admission exhibited a higher weekly weight gain during treatment but did not show better outcome in eating disorder-specific psychopathology and depression. CONCLUSIONS: Motivation to change is an important predictor of short-term outcome with respect to weight gain trajectory during treatment of adolescent AN. As patients with a higher BMI at admission and those with more severe eating disorder-specific symptoms seem to be less motivated to change, the crucial issue of motivation to change should be addressed with these patients during the therapeutic process. PMID- 26134629 TI - Anticancer activity of stoppin based on a novel peptide delivery system. AB - Stoppin (L1) is a newly identified anticancer peptide, which is a potent p53 MDM2/MDMX inhibitor. Due to its limitation in cell delivery efficiency, a new peptide delivery system was developed based on a nucleic acid-polypeptide liposome complex and its stability and effectiveness in vitro was investigated. The nucleic acid-stoppin-liposome complex was prepared and characterization of the complex was conducted. The stability of the complex was evaluated by enzyme digestion. Following transfection of the A549 cells with the complex, detection of green fluorescent protein (GFP) and luciferase activity was conducted to evaluate transfection efficiency. In addition, the anticancer activity of the complex was determined by 3-(4,5-dimethyl-thiazolyl-2)-2,5 diphenyltetrazolium bromide assay and apoptosis was detected by flow cytometry. The results indicated that the particle size of the complex was 102+/-10 nm and the encapsulation rate was ~100% when the ratio of liposome, L1 and plasmid was: 4 ul:1 ug:2 ug. The enzyme digestion experiment demonstrated that the complex was resistant to pancreatic and DNA enzyme degradation, indicating that the complex had biological stability. Cell transfection demonstrated that it had a mutual promotion effect on delivery, which could be confirmed by GFP fluorescence and luciferase assay. The cell-killing efficiency of this novel delivery system was three times higher than with stoppin alone at a low concentration. In conclusion, this novel stoppin peptide delivery system was stable. The nucleic acid-peptide-liposome complex can protect the internal component from the degradation of enzymes, promote entry of the peptide into the cells and enhance the anti-tumor activity of stoppin. Therefore, it is a promising approach for peptide delivery, which can be characterized and visualized using plasmids with GFP or luciferase. PMID- 26134630 TI - STAT6-Dependent Collagen Synthesis in Human Fibroblasts Is Induced by Bovine Milk. AB - Since the domestication of the urus, 10.000 years ago, mankind utilizes bovine milk for different purposes. Besides usage as a nutrient also the external application of milk on skin has a long tradition going back to at least the ancient Aegypt with Cleopatra VII as a great exponent. In order to test whether milk has impact on skin physiology, cultures of human skin fibroblasts were exposed to commercial bovine milk. Our data show significant induction of proliferation by milk (max. 2,3-fold, EC50: 2,5% milk) without toxic effects. Surprisingly, bovine milk was identified as strong inducer of collagen 1A1 synthesis at both, the protein (4-fold, EC50: 0,09% milk) and promoter level. Regarding the underlying molecular pathways, we show functional activation of STAT6 in a p44/42 and p38-dependent manner. More upstream, we identified IGF-1 and insulin as key factors responsible for milk-induced collagen synthesis. These findings show that bovine milk contains bioactive molecules that act on human skin cells. Therefore, it is tempting to test the herein introduced concept in treatment of atrophic skin conditions induced e.g. by UV light or corticosteroids. PMID- 26134631 TI - Detoxification mechanisms of honey bees (Apis mellifera) resulting in tolerance of dietary nicotine. AB - Insecticides are thought to be among the major factors contributing to current declines in bee populations. However, detoxification mechanisms in healthy, unstressed honey bees are poorly characterised. Alkaloids are naturally encountered in pollen and nectar, and we used nicotine as a model compound to identify the mechanisms involved in detoxification processes in honey bees. Nicotine and neonicotinoids have similar modes of action in insects. Our metabolomic and proteomic analyses show active detoxification of nicotine in bees, associated with increased energetic investment and also antioxidant and heat shock responses. The increased energetic investment is significant in view of the interactions of pesticides with diseases such as Nosema spp which cause energetic stress and possible malnutrition. Understanding how healthy honey bees process dietary toxins under unstressed conditions will help clarify how pesticides, alone or in synergy with other stress factors, lead to declines in bee vitality. PMID- 26134632 TI - Protein conformational plasticity and complex ligand-binding kinetics explored by atomistic simulations and Markov models. AB - Understanding the structural mechanisms of protein-ligand binding and their dependence on protein sequence and conformation is of fundamental importance for biomedical research. Here we investigate the interplay of conformational change and ligand-binding kinetics for the serine protease Trypsin and its competitive inhibitor Benzamidine with an extensive set of 150 MUs molecular dynamics simulation data, analysed using a Markov state model. Seven metastable conformations with different binding pocket structures are found that interconvert at timescales of tens of microseconds. These conformations differ in their substrate-binding affinities and binding/dissociation rates. For each metastable state, corresponding solved structures of Trypsin mutants or similar serine proteases are contained in the protein data bank. Thus, our wild-type simulations explore a space of conformations that can be individually stabilized by adding ligands or making suitable changes in protein sequence. These findings provide direct evidence of conformational plasticity in receptors. PMID- 26134633 TI - A novel in situ permeation system and its utility in cancer tissue ablation. AB - Focal ablation therapy is an emerging treatment modality for localized cancer lesions. It is an attractive strategy for inhibiting tumor progression and preventing morbidity associated with open surgery. As for intratissue drug delivery systems for use in local therapy, the convection-enhanced delivery (CED) of liquid drugs has been utilized, particularly for the treatment of malignant brain tumors. Although the conventional CED system is useful for providing drug/vehicle-based local therapy, there are several reported disadvantages in terms of the ability to control the extent of drug diffusion. We herein developed and validated a novel in situ permeation (ISP)-MW-1 system for achieving intratissue drug diffusion. The ISP system includes a perfusion catheter connected to an injector and aspirator, which enables intratissue perfusion of the solute diluted in the vehicle in the tip-inserted cavity. We subsequently evaluated the utility of the ISP-MW-1 system for in situ permeation in a subcutaneous tumor model in hamsters. Dehydrated ethanol, saline and 50% acetic acid were evaluated as the vehicle, and methylene blue was used as a dissolved substance for evaluating the diffusion of the agent. As a result, almost all of the tumor tissue within the capsule (tumor size: ~3 cm) was permeated with the dehydrated ethanol and 50% acetic acid and partially with the saline. We further demonstrated that ISP treatment with 50% acetic acid completely ablated the subcutaneous tumors in all of the treated hamsters (n=3). Therefore, the ISP-MW-1 system is a promising approach for controlling the intratissue diffusion of therapeutic agents and for providing local ablation therapy for cancer lesions. We believe that this system may be applicable to a broad range of medicinal and industrial fields, such as regenerative medicine, drug delivery systems, biochemistry and material technologies as well as cancer therapy. PMID- 26134634 TI - Seasonal variations in the regiodistribution of oil extracted from small-spotted catshark and bogue. AB - The aim of this work was to seasonally characterize the nutritional quality of oil extracted from small-spotted catshark (Scyliorhinus canicula) and bogue (Boops boops). The proximate composition, lipid profile and regiodistribution of the fatty acid in the glycerol backbone were analyzed. In addition, three nutritional indexes were calculated (atherogenicity and thrombogenicity indexes and the hypocholesterolaemic/hypercholesterolaemic ratio). Both species presented PUFA as the predominant fraction, the most abundant being DHA. Healthy values of the aforementioned indexes were maintained throughout the year. Moreover, the relative composition of omega 3 fatty acids at the sn-2 position ranged from 47.3 to 66.8 mol%, attracting interest in the employment of these oils as the raw source for the production of 2-monoacylglycerols. Regarding the individual behavior of each fatty acid, DHA presented a high tendency to occupy the sn-2 bond, whereas EPA presented the opposite behavior. PMID- 26134636 TI - Early Events of Synapse Disassembly in the Damaged Retina. PMID- 26134635 TI - Renal Denervation for Resistant Hypertension: Past, Present, and Future. AB - Renal denervation (RDN) for treatment of resistant hypertension was introduced only 5 years ago. A clear pathophysiological role of renal sympathetic activity for the initiation and maintenance of hypertension and promising data showing a substantial and sustained blood pressure (BP) reduction after RDN has promoted the widespread use of the method at least in Europe. However, in a pivotal trial that included a sham-control group, no significant BP lowering effects was observed. Afterwards, it became clear that methodological issues and poor performance and execution of the intervention have hampered the results of Symplicity HTN-3 study, thereby limiting its validity profoundly. Now, in 2015, the renaissance of RDN has begun and new randomized prospective clinical trials have or will be started soon. In the meantime, it may be wise not to ignore all previous findings, as a rescue therapy for treatment resistant hypertension. A new science era emerged, with changes of the interventional approach and selection of patients potentially profiting most from RDN. PMID- 26134637 TI - The Interactions between Bitter and Sweet Taste Processing in Drosophila. PMID- 26134638 TI - Parvalbumin-Positive Inhibitory Interneurons Oppose Propagation But Favor Generation of Focal Epileptiform Activity. AB - Parvalbumin (Pv)-positive inhibitory interneurons effectively control network excitability, and their optogenetic activation has been reported to block epileptic seizures. An intense activity in GABAergic interneurons, including Pv interneurons, before seizures has been described in different experimental models of epilepsy, raising the hypothesis that an increased GABAergic inhibitory signal may, under certain conditions, initiate seizures. It is therefore unclear whether the activity of Pv interneurons enhances or opposes epileptiform activities. Here we use a mouse cortical slice model of focal epilepsy in which the epileptogenic focus can be identified and the role of Pv interneurons in the generation and propagation of seizure-like ictal events is accurately analyzed by a combination of optogenetic, electrophysiological, and imaging techniques. We found that a selective activation of Pv interneurons at the focus failed to block ictal generation and induced postinhibitory rebound spiking in pyramidal neurons, enhancing neuronal synchrony and promoting ictal generation. In contrast, a selective activation of Pv interneurons distant from the focus blocked ictal propagation and shortened ictal duration at the focus. We revealed that the reduced ictal duration was a direct consequence of the ictal propagation block, probably by preventing newly generated afterdischarges to travel backwards to the original focus of ictal initiation. Similar results were obtained upon individual Pv interneuron activation by intracellular depolarizing current pulses. The functional dichotomy of Pv interneurons here described opens new perspectives to our understanding of how local inhibitory circuits govern generation and spread of focal epileptiform activities. PMID- 26134639 TI - NMDA Receptor Plasticity in the Hypothalamic Paraventricular Nucleus Contributes to the Elevated Blood Pressure Produced by Angiotensin II. AB - Hypertension induced by angiotensin II (Ang II) is associated with glutamate dependent dysregulation of the hypothalamic paraventricular nucleus (PVN). Many forms of glutamate-dependent plasticity are mediated by NMDA receptor GluN1 subunit expression and the distribution of functional receptor to the plasma membrane of dendrites. Here, we use a combined ultrastructural and functional analysis to examine the relationship between PVN NMDA receptors and the blood pressure increase induced by chronic infusion of a low dose of Ang II. We report that the increase in blood pressure produced by a 2 week administration of a subpressor dose of Ang II results in an elevation in plasma membrane GluN1 in dendrites of PVN neurons in adult male mice. The functional implications of these observations are further demonstrated by the finding that GluN1 deletion in PVN neurons attenuated the Ang II-induced increases in blood pressure. These results indicate that NMDA receptor plasticity in PVN neurons significantly contributes to the elevated blood pressure mediated by Ang II. PMID- 26134640 TI - Explicit and Implicit Processes Constitute the Fast and Slow Processes of Sensorimotor Learning. AB - A popular model of human sensorimotor learning suggests that a fast process and a slow process work in parallel to produce the canonical learning curve (Smith et al., 2006). Recent evidence supports the subdivision of sensorimotor learning into explicit and implicit processes that simultaneously subserve task performance (Taylor et al., 2014). We set out to test whether these two accounts of learning processes are homologous. Using a recently developed method to assay explicit and implicit learning directly in a sensorimotor task, along with a computational modeling analysis, we show that the fast process closely resembles explicit learning and the slow process approximates implicit learning. In addition, we provide evidence for a subdivision of the slow/implicit process into distinct manifestations of motor memory. We conclude that the two-state model of motor learning is a close approximation of sensorimotor learning, but it is unable to describe adequately the various implicit learning operations that forge the learning curve. Our results suggest that a wider net be cast in the search for the putative psychological mechanisms and neural substrates underlying the multiplicity of processes involved in motor learning. PMID- 26134642 TI - Lesser Neural Pattern Similarity across Repeated Tests Is Associated with Better Long-Term Memory Retention. AB - Encoding and retrieval processes enhance long-term memory performance. The efficiency of encoding processes has recently been linked to representational consistency: the reactivation of a representation that gets more specific each time an item is further studied. Here we examined the complementary hypothesis of whether the efficiency of retrieval processes also is linked to representational consistency. Alternatively, recurrent retrieval might foster representational variability--the altering or adding of underlying memory representations. Human participants studied 60 Swahili-Swedish word pairs before being scanned with fMRI the same day and 1 week later. On Day 1, participants were tested three times on each word pair, and on Day 7 each pair was tested once. A BOLD signal change in right superior parietal cortex was associated with subsequent memory on Day 1 and with successful long-term retention on Day 7. A representational similarity analysis in this parietal region revealed that beneficial recurrent retrieval was associated with representational variability, such that the pattern similarity on Day 1 was lower for retrieved words subsequently remembered compared with those subsequently forgotten. This was mirrored by a monotonically decreased BOLD signal change in dorsolateral prefrontal cortex on Day 1 as a function of repeated successful retrieval for words subsequently remembered, but not for words subsequently forgotten. This reduction in prefrontal response could reflect reduced demands on cognitive control. Collectively, the results offer novel insights into why memory retention benefits from repeated retrieval, and they suggest fundamental differences between repeated study and repeated testing. SIGNIFICANCE STATEMENT: Repeated testing is known to produce superior long-term retention of the to-be-learned material compared with repeated encoding and other learning techniques, much because it fosters repeated memory retrieval. This study demonstrates that repeated memory retrieval might strengthen memory by inducing more differentiated or elaborated memory representations in the parietal cortex, and at the same time reducing demands on prefrontal-cortex-mediated cognitive control processes during retrieval. The findings contrast with recent demonstrations that repeated encoding induces less differentiated or elaborated memory representations. Together, this study suggests a potential neurocognitive explanation of why repeated retrieval is more beneficial for long-term retention than repeated encoding, a phenomenon known as the testing effect. PMID- 26134641 TI - Pronociceptive and Antinociceptive Effects of Buprenorphine in the Spinal Cord Dorsal Horn Cover a Dose Range of Four Orders of Magnitude. AB - Due to its distinct pharmacological profile and lower incidence of adverse events compared with other opioids, buprenorphine is considered a safe option for pain and substitution therapy. However, despite its wide clinical use, little is known about the synaptic effects of buprenorphine in nociceptive pathways. Here, we demonstrate dose-dependent, bimodal effects of buprenorphine on transmission at C fiber synapses in rat spinal cord dorsal horn in vivo. At an analgesically active dose of 1500 MUg.kg(-1), buprenorphine reduced the strength of spinal C-fiber synapses. This depression required activation of spinal opioid receptors, putatively MU1-opioid receptors, as indicated by its sensitivity to spinal naloxone and to the selective MU1-opioid receptor antagonist naloxonazine. In contrast, a 15,000-fold lower dose of buprenorphine (0.1 MUg.kg(-1)), which caused thermal and mechanical hyperalgesia in behaving animals, induced an enhancement of transmission at spinal C-fiber synapses. The ultra-low-dose buprenorphine-induced synaptic facilitation was mediated by supraspinal naloxonazine-insensitive, but CTOP-sensitive MU-opioid receptors, descending serotonergic pathways, and activation of spinal glial cells. Selective inhibition of spinal 5-hydroxytryptamine-2 receptors (5-HT2Rs), putatively located on spinal astrocytes, abolished both the induction of synaptic facilitation and the hyperalgesia elicited by ultra-low-dose buprenorphine. Our study revealed that buprenorphine mediates its modulatory effects on transmission at spinal C-fiber synapses by dose dependently acting on distinct MU-opioid receptor subtypes located at different levels of the neuraxis. PMID- 26134643 TI - Theta Oscillations in Visual Cortex Emerge with Experience to Convey Expected Reward Time and Experienced Reward Rate. AB - The primary visual cortex (V1) is widely regarded as faithfully conveying the physical properties of visual stimuli. Thus, experience-induced changes in V1 are often interpreted as improving visual perception (i.e., perceptual learning). Here we describe how, with experience, cue-evoked oscillations emerge in V1 to convey expected reward time as well as to relate experienced reward rate. We show, in chronic multisite local field potential recordings from rat V1, that repeated presentation of visual cues induces the emergence of visually evoked oscillatory activity. Early in training, the visually evoked oscillations relate to the physical parameters of the stimuli. However, with training, the oscillations evolve to relate the time in which those stimuli foretell expected reward. Moreover, the oscillation prevalence reflects the reward rate recently experienced by the animal. Thus, training induces experience-dependent changes in V1 activity that relate to what those stimuli have come to signify behaviorally: when to expect future reward and at what rate. PMID- 26134644 TI - Prefrontal and Striatal Glutamate Differently Relate to Striatal Dopamine: Potential Regulatory Mechanisms of Striatal Presynaptic Dopamine Function? AB - Theoretical and animal work has proposed that prefrontal cortex (PFC) glutamate inhibits dopaminergic inputs to the ventral striatum (VS) indirectly, whereas direct VS glutamatergic afferents have been suggested to enhance dopaminergic inputs to the VS. In the present study, we aimed to investigate relationships of glutamate and dopamine measures in prefrontostriatal circuitries of healthy humans. We hypothesized that PFC and VS glutamate, as well as their balance, are differently associated with VS dopamine. Glutamate concentrations in the left lateral PFC and left striatum were assessed using 3-Tesla proton magnetic resonance spectroscopy. Striatal presynaptic dopamine synthesis capacity was measured by fluorine-18-l-dihydroxyphenylalanine (F-18-FDOPA) positron emission tomography. First, a negative relationship was observed between glutamate concentrations in lateral PFC and VS dopamine synthesis capacity (n = 28). Second, a positive relationship was revealed between striatal glutamate and VS dopamine synthesis capacity (n = 26). Additionally, the intraindividual difference between PFC and striatal glutamate concentrations correlated negatively with VS dopamine synthesis capacity (n = 24). The present results indicate an involvement of a balance in PFC and striatal glutamate in the regulation of VS dopamine synthesis capacity. This notion points toward a potential mechanism how VS presynaptic dopamine levels are kept in a fine-tuned range. A disruption of this mechanism may account for alterations in striatal dopamine turnover as observed in mental diseases (e.g., in schizophrenia). SIGNIFICANCE STATEMENT: The present work demonstrates complementary relationships between prefrontal and striatal glutamate and ventral striatal presynaptic dopamine using human imaging measures: a negative correlation between prefrontal glutamate and presynaptic dopamine and a positive relationship between striatal glutamate and presynaptic dopamine are revealed. The results may reflect a regulatory role of prefrontal and striatal glutamate for ventral striatal presynaptic dopamine levels. Such glutamate-dopamine relationships improve our understanding of neurochemical interactions in prefrontostriatal circuits and have implications for the neurobiology of mental disease. PMID- 26134645 TI - Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus. AB - Development of novel disease-modifying treatment strategies for neurological disorders, which at present have no cure, represents a major challenge for today's neurology. Translation of findings from animal models to humans represents an unresolved gap in most of the preclinical studies. Gene therapy is an evolving innovative approach that may prove useful for clinical applications. In animal models of temporal lobe epilepsy (TLE), gene therapy treatments based on viral vectors encoding NPY or galanin have been shown to effectively suppress seizures. However, how this translates to human TLE remains unknown. A unique possibility to validate these animal studies is provided by a surgical therapeutic approach, whereby resected epileptic tissue from temporal lobes of pharmacoresistant patients are available for neurophysiological studies in vitro. To test whether NPY and galanin have antiepileptic actions in human epileptic tissue as well, we applied these neuropeptides directly to human hippocampal slices in vitro. NPY strongly decreased stimulation-induced EPSPs in dentate gyrus and CA1 (up to 30 and 55%, respectively) via Y2 receptors, while galanin had no significant effect. Receptor autoradiographic binding revealed the presence of both NPY and galanin receptors, while functional receptor binding was only detected for NPY, suggesting that galanin receptor signaling may be impaired. These results underline the importance of validating findings from animal studies in human brain tissue, and advocate for NPY as a more appropriate candidate than galanin for future gene therapy trials in pharmacoresistant TLE patients. PMID- 26134646 TI - Spontaneous Vesicle Release Is Not Tightly Coupled to Voltage-Gated Calcium Channel-Mediated Ca2+ Influx and Is Triggered by a Ca2+ Sensor Other Than Synaptotagmin-2 at the Juvenile Mice Calyx of Held Synapses. AB - It is well known that voltage-gated calcium channels (VGCCs)-mediated Ca(2+) influx triggers evoked synaptic vesicle release. However, the mechanisms of Ca(2+) regulation of spontaneous miniature vesicle release (mini) remain poorly understood. Here we show that blocking VGCCs at the juvenile mice (C57BL/6) calyx of Held synapse failed to cause an immediate change in minis. Instead, it resulted in a significant reduction (~40%) of mini frequency several minutes after the blockage. By recording VGCC activity and single vesicle fusion events directly at the presynaptic terminal, we found that minis did not couple to VGCC mediated Ca(2+) entry, arguing for a lack of direct correlation between mini and transient Ca(2+) influx. Moreover, mini frequencies displayed a lower apparent Ca(2+) cooperativity than those of evoked release. In agreement with this observation, abrogation of the Ca(2+) sensor synaptotagmin-2 had no effect on apparent Ca(2+) cooperativity of minis. Together, our study provides the first direct evidence that spontaneous minis are not mediated by transient Ca(2+) signals through VGCCs and are triggered by a Ca(2+)-sensing mechanism that is different from the evoked release at these microdomain VGCC-vesicle coupled synapses. PMID- 26134647 TI - A Selective Role for Lmo4 in Cue-Reward Learning. AB - The ability to use environmental cues to predict rewarding events is essential to survival. The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the underlying molecular mechanisms can inform strategies for intervention. The transcriptional regulator LIM-only 4 (LMO4) is highly expressed in pyramidal neurons of the BLA, where it plays an important role in fear learning. Because the BLA also contributes to cue reward learning, we investigated the role of BLA LMO4 in this process using Lmo4 deficient mice and RNA interference. Lmo4-deficient mice showed a selective deficit in conditioned reinforcement. Knockdown of LMO4 in the BLA, but not in the nucleus accumbens, recapitulated this deficit in wild-type mice. Molecular and electrophysiological studies identified a deficit in dopamine D2 receptor signaling in the BLA of Lmo4-deficient mice. These results reveal a novel, LMO4 dependent transcriptional program within the BLA that is essential to cue-reward learning. PMID- 26134648 TI - Autism-Associated Insertion Mutation (InsG) of Shank3 Exon 21 Causes Impaired Synaptic Transmission and Behavioral Deficits. AB - SHANK3 (also known as PROSAP2) is a postsynaptic scaffolding protein at excitatory synapses in which mutations and deletions have been implicated in patients with idiopathic autism, Phelan-McDermid (aka 22q13 microdeletion) syndrome, and other neuropsychiatric disorders. In this study, we have created a novel mouse model of human autism caused by the insertion of a single guanine nucleotide into exon 21 (Shank3(G)). The resulting frameshift causes a premature STOP codon and loss of major higher molecular weight Shank3 isoforms at the synapse. Shank3(G/G) mice exhibit deficits in hippocampus-dependent spatial learning, impaired motor coordination, altered response to novelty, and sensory processing deficits. At the cellular level, Shank3(G/G) mice also exhibit impaired hippocampal excitatory transmission and plasticity as well as changes in baseline NMDA receptor-mediated synaptic responses. This work identifies clear alterations in synaptic function and behavior in a novel, genetically accurate mouse model of autism mimicking an autism-associated insertion mutation. Furthermore, these findings lay the foundation for future studies aimed to validate and study region-selective and temporally selective genetic reversal studies in the Shank3(G/G) mouse that was engineered with such future experiments in mind. PMID- 26134650 TI - alpha6-Containing GABAA Receptors Are the Principal Mediators of Inhibitory Synapse Strengthening by Insulin in Cerebellar Granule Cells. AB - Activity-dependent strengthening of central synapses is a key factor driving neuronal circuit behavior in the vertebrate CNS. At fast inhibitory synapses, strengthening is thought to occur by increasing the number of GABAA receptors (GABARs) of the same subunit composition to preexisting synapses. Here, we show that strengthening of mouse cerebellar granule cell GABAergic synapses occurs by a different mechanism. Specifically, we show that the neuropeptide hormone, insulin, strengthens inhibitory synapses by recruiting alpha6-containing GABARs rather than accumulating more alpha1-containing receptors that are resident to the synapse. Because alpha6-receptors are targeted to functionally distinct postsynaptic sites from alpha1-receptors, we conclude that only a subset of all inhibitory synapses are strengthened. Together with our recent findings on stellate cells, we propose a general mechanism by which mature inhibitory synapses are strengthened. In this scenario, alpha1-GABARs resident to inhibitory synapses form the hardwiring of neuronal circuits with receptors of a different composition fulfilling a fundamental, but unappreciated, role in synapse strengthening. PMID- 26134649 TI - Inactivation of Primate Prefrontal Cortex Impairs Auditory and Audiovisual Working Memory. AB - The prefrontal cortex is associated with cognitive functions that include planning, reasoning, decision-making, working memory, and communication. Neurophysiology and neuropsychology studies have established that dorsolateral prefrontal cortex is essential in spatial working memory while the ventral frontal lobe processes language and communication signals. Single-unit recordings in nonhuman primates has shown that ventral prefrontal (VLPFC) neurons integrate face and vocal information and are active during audiovisual working memory. However, whether VLPFC is essential in remembering face and voice information is unknown. We therefore trained nonhuman primates in an audiovisual working memory paradigm using naturalistic face-vocalization movies as memoranda. We inactivated VLPFC, with reversible cortical cooling, and examined performance when faces, vocalizations or both faces and vocalization had to be remembered. We found that VLPFC inactivation impaired subjects' performance in audiovisual and auditory alone versions of the task. In contrast, VLPFC inactivation did not disrupt visual working memory. Our studies demonstrate the importance of VLPFC in auditory and audiovisual working memory for social stimuli but suggest a different role for VLPFC in unimodal visual processing. SIGNIFICANCE STATEMENT: The ventral frontal lobe, or inferior frontal gyrus, plays an important role in audiovisual communication in the human brain. Studies with nonhuman primates have found that neurons within ventral prefrontal cortex (VLPFC) encode both faces and vocalizations and that VLPFC is active when animals need to remember these social stimuli. In the present study, we temporarily inactivated VLPFC by cooling the cortex while nonhuman primates performed a working memory task. This impaired the ability of subjects to remember a face and vocalization pair or just the vocalization alone. Our work highlights the importance of the primate VLPFC in the processing of faces and vocalizations in a manner that is similar to the inferior frontal gyrus in the human brain. PMID- 26134651 TI - Individual Differences in Temporal Summation of Pain Reflect Pronociceptive and Antinociceptive Brain Structure and Function. AB - Temporal summation of pain (TSP), the perception of increasingly greater pain evoked by repetitive noxious stimuli, is highly variable between individuals. Individuals with facilitated pain processing and/or reduced pain-modulatory capabilities are regarded as pronociceptive, whereas individuals with reduced pain processing capacity are characterized as antinociceptive. Brodmann area (BA) 3a of the primary somatosensory cortex is part of an ascending pathway from the sensory thalamus that mediates TSP. Descending pain modulation involves projections from the subgenual anterior cingulate cortex (sgACC) to the periaqueductal gray to the rostral ventromedial medulla (RVM). Here, we tested the hypothesis that pronociceptive individuals have an enhanced TSP response compared with antinociceptive individuals, marked by facilitated ascending nociceptive processing and/or reduced capacity for descending pain modulation. Eighty healthy humans were tested with a TSP protocol and underwent structural and resting-state functional magnetic resonance imaging. We found large interindividual differences in TSP responses, which were positively correlated with functional connectivity (FC) between individuals' right sensory thalamus with their BA 3a (thal-BA 3a), and with cortical thickness in their insula and medial prefrontal cortex. In contrast, TSP was negatively correlated with FC between individuals' RVM with their sgACC (RVM-sgACC). When subjects were grouped as pronociceptive or antinociceptive based on whether they had greater thal-BA 3a or RVM-sgACC FC respectively, pronociceptive subjects showed greater TSP responses. Furthermore, TSP was positively correlated with the extent of imbalance toward ascending nociceptive processing. Our study indicates that individuals with enhanced TSP have facilitated ascending nociceptive processing and reduced pain-modulatory capacities. SIGNIFICANCE STATEMENT: This study provides novel evidence that an individual's propensity to experience amplified pain with repeated stimuli [i.e., temporal summation of pain (TSP)] reflects attributes of their "pain connectome," namely stronger ascending nociceptive and weaker descending pain-modulatory components. Understanding the individual neural mechanisms underlying TSP within individuals has implications for developing personalized pain-management strategies for chronic pain. PMID- 26134652 TI - Re-Emergent Inhibition of Cochlear Inner Hair Cells in a Mouse Model of Hearing Loss. AB - Hearing loss among the elderly correlates with diminished social, mental, and physical health. Age-related cochlear cell death does occur, but growing anatomical evidence suggests that synaptic rearrangements on sensory hair cells also contribute to auditory functional decline. Here we present voltage-clamp recordings from inner hair cells of the C57BL/6J mouse model of age-related hearing loss, which reveal that cholinergic synaptic inputs re-emerge during aging. These efferents are functionally inhibitory, using the same ionic mechanisms as do efferent contacts present transiently before the developmental onset of hearing. The strength of efferent inhibition of inner hair cells increases with hearing threshold elevation. These data indicate that the aged cochlea regains features of the developing cochlea and that efferent inhibition of the primary receptors of the auditory system re-emerges with hearing impairment. SIGNIFICANCE STATEMENT: Synaptic changes in the auditory periphery are increasingly recognized as important factors in hearing loss. To date, anatomical work has described the loss of afferent contacts from cochlear hair cells. However, relatively little is known about the efferent innervation of the cochlea during hearing loss. We performed intracellular recordings from mouse inner hair cells across the lifespan and show that efferent innervation of inner hair cells arises in parallel with the loss of afferent contacts and elevated hearing threshold during aging. These efferent neurons inhibit inner hair cells, raising the possibility that they play a role in the progression of age-related hearing loss. PMID- 26134654 TI - Transsynaptic Tracing from Taste Receptor Cells Reveals Local Taste Receptor Gene Expression in Gustatory Ganglia and Brain. AB - Taste perception begins in the oral cavity by interactions of taste stimuli with specific receptors. Specific subsets of taste receptor cells (TRCs) are activated upon tastant stimulation and transmit taste signals to afferent nerve fibers and ultimately to the brain. How specific TRCs impinge on the innervating nerves and how the activation of a subset of TRCs leads to the discrimination of tastants of different qualities and intensities is incompletely understood. To investigate the organization of taste circuits, we used gene targeting to express the transsynaptic tracer barley lectin (BL) in the gustatory system of mice. Because TRCs are not synaptically connected with the afferent nerve fibers, we first analyzed tracer production and transfer within the taste buds (TBs). Surprisingly, we found that BL is laterally transferred across all cell types in TBs of mice expressing the tracer under control of the endogenous Tas1r1 and Tas2r131 promotor, respectively. Furthermore, although we detected the BL tracer in both ganglia and brain, we also found local low-level Tas1r1 and Tas2r131 gene, and thus tracer expression in these tissues. Finally, we identified the Tas1r1 and Tas2r131-expressing cells in the peripheral and CNS using a binary genetic approach. Together, our data demonstrate that genetic transsynaptic tracing from bitter and umami receptor cells does not selectively label taste specific neuronal circuits and reveal local taste receptor gene expression in the gustatory ganglia and the brain. SIGNIFICANCE STATEMENT: Previous papers described the organization of taste pathways in mice expressing a transsynaptic tracer from transgenes in bitter or sweet/umami-sensing taste receptor cells. However, reported results differ dramatically regarding the numbers of synapses crossed and the reduction of signal intensity after each transfer step. Nevertheless, all groups claimed this approach appropriate for quality-specific visualization of taste pathways. In the present study, we demonstrate that genetic transsynaptic tracing originating from umami and bitter taste receptor cells does not selectively label taste quality-specific neuronal circuits due to lateral transfer of the tracer in the taste bud and taste receptor expression in sensory ganglia and brain. Moreover, we visualized for the first time taste receptor-expressing cells in the PNS and CNS. PMID- 26134653 TI - Etomidate Impairs Long-Term Potentiation In Vitro by Targeting alpha5-Subunit Containing GABAA Receptors on Nonpyramidal Cells. AB - Previous experiments using genetic and pharmacological manipulations have provided strong evidence that etomidate impairs synaptic plasticity and memory by modulating alpha5-subunit containing GABAA receptors (alpha5-GABAARs). Because alpha5-GABAARs mediate tonic inhibition (TI) in hippocampal CA1 pyramidal cells and etomidate enhances TI, etomidate enhancement of TI in pyramidal cells has been proposed as the underlying mechanism (Martin et al., 2009). Here we tested this hypothesis by selectively removing alpha5-GABAARs from pyramidal neurons (CA1-pyr-alpha5-KO) and comparing the ability of etomidate to enhance TI and block LTP in fl-alpha5 (WT), global-alpha5-KO (gl-alpha5-KO), and CA1-pyr-alpha5 KO mice. Etomidate suppressed LTP in slices from WT and CA1-pyr-alpha5-KO but not gl-alpha5-KO mice. There was a trend toward reduced TI in both gl-alpha5-KO and CA1-pyr-alpha5-KO mice, but etomidate enhanced TI to similar levels in all genotypes. The dissociation between effects of etomidate on TI and LTP in gl alpha5-KO mice indicates that increased TI in pyramidal neurons is not the mechanism by which etomidate impairs LTP and memory. Rather, the ability of etomidate to block LTP in WT and CA1-pyr-alpha5-KO mice, but not in gl-alpha5-KO mice, points toward alpha5-GABAARs on nonpyramidal cells as the essential effectors controlling plasticity in this in vitro model of learning and memory. PMID- 26134656 TI - proBDNF and p75NTR Control Excitability and Persistent Firing of Cortical Pyramidal Neurons. AB - Persistent firing of entorhinal cortex (EC) pyramidal neurons is a key component of working and spatial memory. We report here that a pro-brain-derived neurotrophic factor (proBDNF)-dependent p75NTR signaling pathway plays a major role in excitability and persistent activity of pyramidal neurons in layer V of the EC. Using electrophysiological recordings, we show that proBDNF suppresses persistent firing in entorhinal slices from wild-type mice but not from p75NTR null mice. Conversely, function-blocking proBDNF antibodies enhance excitability of pyramidal neurons and facilitate their persistent firing, and acute exposure to function-blocking p75NTR antibodies results in enhanced firing activity of pyramidal neurons. Genetic deletion of p75NTR specifically in neurons or during adulthood also induces enhanced excitability and persistent activity, indicating that the proBDNF-p75NTR signaling cascade functions within adult neurons to inhibit pyramidal activity. Phosphatidylinositol 4,5-bisphosphate (PIP2) sensitive transient receptor potential canonical channels play a critical role in mediating persistent firing in the EC and we hypothesized that proBDNF-dependent p75NTR activation regulates PIP2 levels. Accordingly, proBDNF decreases cholinergic calcium responses in cortical neurons and affects carbachol-induced depletion of PIP2. Further, we show that the modulation of persistent firing by proBDNF relies on a p75NTR-Rac1-PI4K pathway. The hypothesis that proBDNF and p75NTR maintain network homeostasis in the adult CNS was tested in vivo and we report that p75NTR-null mice show improvements in working memory but also display an increased propensity for severe seizures. We propose that the proBDNF-p75NTR axis controls pyramidal neuron excitability and persistent activity to balance EC performance with the risk of runaway activity. SIGNIFICANCE STATEMENT: Persistent firing of entorhinal cortex (EC) pyramidal neurons is required for working memory. We report here that pro-brain-derived neurotrophic factor (proBDNF) activates p75NTR to induce a Rac1-dependent and phosphatidylinositol 4,5 bisphosphate-dependent signaling cascade that suppresses persistent activity. Conversely, using loss-of-function approaches, we find that endogenous proBDNF or p75NTR activation strongly decreases pyramidal neuron excitability and persistent firing, suggesting that a physiological role of this proBDNF-p75NTR cascade may be to regulate working memory in vivo. Consistent with this, mice rendered null for p75NTR during adulthood show improvements in working memory but also display an increased propensity for severe seizures. We propose that by attenuating EC network performance, the proBDNF-p75NTR signaling cascade reduces the probability of epileptogenesis. PMID- 26134657 TI - Pten Deletion Promotes Regrowth of Corticospinal Tract Axons 1 Year after Spinal Cord Injury. AB - Chronic spinal cord injury (SCI) is a formidable hurdle that prevents a large number of injured axons from crossing the lesion, particularly the corticospinal tract (CST). This study shows that Pten deletion in the adult mouse cortex enhances compensatory sprouting of uninjured CST axons. Furthermore, forced upregulation of mammalian target of rapamycin (mTOR) initiated either 1 month or 1 year after injury promoted regeneration of CST axons. Our results indicate that both developmental and injury-induced mTOR downregulation in corticospinal motor neurons can be reversed in adults. Modulating neuronal mTOR activity is a potential strategy for axon regeneration after chronic SCI. SIGNIFICANCE STATEMENT: As one of the long descending tracts controlling voluntary movement, the corticospinal tract (CST) plays an important role for functional recovery after spinal cord injury. The regeneration of CST has been a major challenge in the field, especially after chronic injuries. Here we developed a strategy to modulate Pten/mammalian target of rapamycin signaling in adult corticospinal motor neurons in the postinjury paradigm. It not only promoted the sprouting of uninjured CST axons, but also enabled the regeneration of injured axons past the lesion in a mouse model of spinal cord injury, even when treatment was delayed up to 1 year after the original injury. The results considerably extend the window of opportunity for regenerating CST axons severed in spinal cord injuries. PMID- 26134655 TI - Increased Basolateral Amygdala Pyramidal Cell Excitability May Contribute to the Anxiogenic Phenotype Induced by Chronic Early-Life Stress. AB - Adolescence represents a particularly vulnerable period during which exposure to stressors can precipitate the onset of psychiatric disorders and addiction. The basolateral amygdala (BLA) plays an integral role in the pathophysiology of anxiety and addiction. Acute and chronic stress promote increases in BLA pyramidal cell firing, and decreasing BLA excitability alleviates anxiety measures in humans and rodents. Notably, the impact of early-life stress on the mechanisms that govern BLA excitability is unknown. To address this gap in our knowledge, we used a rodent model of chronic early-life stress that engenders robust and enduring increases in anxiety-like behaviors and ethanol intake and examined the impact of this model on the intrinsic excitability of BLA pyramidal cells. Adolescent social isolation was associated with a significant increase in the intrinsic excitability of BLA pyramidal cells and a blunting of the medium component of the afterhyperpolarization potential, a voltage signature of calcium activated potassium (Kca) channel activity. Western blot analysis revealed reduced expression of small-conductance Kca (SK) channel protein in the BLA of socially isolated (SI) rats. Bath application of a positive SK channel modulator (1-EBIO) normalized firing in ex vivo recordings from SI rats, and in vivo intra BLA 1-EBIO infusion reduced anxiety-like behaviors. These findings reveal that chronic adolescent stress impairs SK channel function, which contributes to an increase in BLA pyramidal cell excitability and highlights BLA SK channels as promising targets for the treatment of anxiety disorders and comorbid addiction. SIGNIFICANCE STATEMENT: Although anxiety disorders and alcohol addiction frequently co-occur, the mechanisms that contribute to this comorbidity are poorly understood. Here, we used a rodent early-life stress model that leads to robust and longlasting increases in behaviors associated with elevated risk of anxiety disorders and addiction to identify novel neurobiological substrates that may underlie these behaviors. Our studies focused on the primary output neurons of the basolateral amygdala, a brain region that plays a key role in anxiety and addiction. We discovered that early-life stress decreases the activity of a specific class of potassium channels and increases the intrinsic excitability of BLA neurons and present evidence that enhancing the function of these channels normalizes BLA excitability and attenuates anxiety-like behaviors. PMID- 26134659 TI - Significantly improving the yield of recombinant proteins in Bacillus subtilis by a novel powerful mutagenesis tool (ARTP): Alkaline alpha-amylase as a case study. AB - In this study, atmospheric and room temperature plasma (ARTP), a promising mutation breeding technique, was successfully applied to generate Bacillus subtilis mutants that yielded large quantities of recombinant protein. The high throughput screening platform was implemented to select those mutants with the highest yield of recombinant alkaline alpha-amylase (AMY), including the preferred mutant B. subtilis WB600 mut-12#. The yield and productivity of recombinant AMY in B. subtilis WB600 mut-12# increased 35.0% and 8.8%, respectively, the extracellular protein concentration of which increased 37.9%. B. subtilis WB600 mut-12# exhibited good genetic stability. Cells from B. subtilis WB600 mut-12# became shorter and wider than those from the wild-type. This study is the first to report a novel powerful mutagenesis tool (ARTP) that significantly improves the yield of recombinant proteins in B. subtilis and may therefore play an important role in the high expression level of proteins in recombinant microbial hosts. PMID- 26134658 TI - miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction. AB - Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR 155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development. PMID- 26134660 TI - Cloning, expression and purification of d-tagatose 3-epimerase gene from Escherichia coli JM109. AB - An unknown d-tagatose 3-epimerase (DTE) containing a IoIE domain was identified and cloned from Escherichia coli. This gene was subcloned into the prokaryotic expression vector pET-15b, and induced by IPTG in E. coli BL21 expression system. Through His-select gel column purification and fast-protein liquid chromatography, highly purified and stable DTE protein was produced. The molecular weight of the DTE protein was estimated to be 29.8kDa. The latest 83 DTE sequences from public database were selected and analyzed by molecular clustering, multi-sequence alignment. DTEs were roughly divided into five categories. PMID- 26134661 TI - Novel macromolecules derived from coumarin: synthesis and antioxidant activity. AB - The rational design of 4-hydroxycoumarins with tailor-made antioxidant activities is required nowadays due to the wide variety of pharmacologically significant, structurally interesting of coumarins and researcher orientation toward green chemistry and natural products. A simple and unique coumarins have been achieved by reaction of 4-hydroxycoumarin with aromatic aldehyde accompanied with the creation of a macromolecules have 2-aminothiazolidin-4-one. The molecular structures of the compounds were characterized by the Fourier transformation infrared and Nuclear magnetic resonance spectroscopies, in addition to CHN analysis. The scavenging abilities of new compounds against stable DPPH radical (DPPH*) and hydrogen peroxide were done and the results show that the compounds exhibited high antioxidant activates. PMID- 26134662 TI - Effects of Running an Ultramarathon on Cardiac, Hematologic, and Metabolic Biomarkers. AB - Serum biomarkers fluctuate as a result of running marathons, but their changes during ultramarathons have not been adequately studied. We collected blood samples from 20 participants before and 21 participants after the 161-km ultramarathon in Leadville, Colorado in August 2013. Using a portable analyzer, we measured cardiac troponin I (cTnl), hematologic, and metabolic biomarkers. Out of 10 runners for whom we collected both pre- and post-race samples, 8 were able to successfully complete the race. Mean cTnl increased from 0.001 to 0.047 ng/mL (p=0.005). Mean sodium decreased from 141 to 138 mmol/L (p <0.01). However, all runners had a sodium of >=135 mmol/L post-race (reference range 138-146 mmol/L). Mean creatinine increased from 0.93 to 1.17 mg/dL (p <0.05). Only one out of 10 runners had an abnormal creatinine level of 1.8 mg/dL post-race (reference range 0.6-1.3 mg/dL). The other parameters did not reach statistical significance. Analyzing the samples from 21 runners after the race revealed that runners who finished the race in faster time had higher cTnl levels compared to those who finished the race close to the 30-hour cut-off finish time (P=0.005). Running an ultramarathon caused significant changes in cardiac and metabolic parameters. Ultramarathon running intensity and finish time may have effects on post-race cTnl level. PMID- 26134663 TI - Validity of the V-cut Test for Young Basketball Players. AB - The aim of the present study was to assess the reliability, usefulness, validity, age-related differences and responsiveness of a 25- m side-step cutting maneuver test (V-cut test). Fifty young male basketball players performed the V-cut test on 2 occasions separated by 5-7 days to assess test-retest reliability and determine a priori usefulness. Twenty subjects also completed both the L-Run and 505 test to analyze the possible relationships among these 3 tests. Furthermore, 33 players performed the V-cut test 4 times throughout the season to analyze responsiveness. Finally, 53 players (U-14 to U-20) were assessed in the V-cut test to examine the age-related differences. Reliability scores showed high intraclass correlation coefficient (ICC=0.90) and low coefficient of variation (CV=1.4%). The responsiveness of the V-cut test was good, as the typical short- (1.5-1.7%), mid- (1.6-3.1%) and long-term (3.3%) changes in V-cut performance were higher than the CV. Low (r=0.64; CL90%: 0.34; 0.82) to moderate (r=0.76; CL90%: 0.53; 0.88) relationships were found between the V-cut test with the 505 and L-Run test, respectively. Age-related differences analysis showed better V cut test performance as age increased in adolescent basketball players. The V-cut test is reliable to assess change of direction ability (CODA) and it could be used to monitor CODA in adolescent basketball players. PMID- 26134664 TI - The Effect of Performing Bi- and Unilateral Row Exercises on Core Muscle Activation. AB - The purpose of the study was to compare core muscle activation in 3 different row exercises (free-weight bent-over row, seated cable row and machine row) performed unilaterally and bilaterally, at matched effort levels. 15 resistance-trained men (26.0+/-4.4 years, 81.0+/-9.5 kg, 1.81+/-0.07 m) performed the exercises in randomized order. For erector spinae and multifidus, EMG activities in unilateral machine- and cable row were 60-63% and 74-78% of the bilateral performance (P<=0.036). For external oblique, the EMG activities recorded during bilateral exercises were 37-41% of the unilateral performance (P<=0.010). In unilateral cable- and machine rows, the EMG activities in external oblique and multifidus were 50-57% and 70-73% of the free-weight row (P<=0.002). In bilateral free weight row, EMG activity in erector spinae was greater than bilateral machine- (+34%, P=0.004) and unilateral free-weight rows (+12%, P=0.016). For rectus abdominis there were no significant differences between conditions. In conclusion, 1) free-weight row provided greater EMG activity in erector spinae (bilaterally and unilaterally) and multifidus (unilaterally) than machine row; 2) unilateral performance of exercises activated the external oblique more than bilateral performance, regardless of exercise; and 3) generally bilateral performance of exercises provided higher erector spinae and multifidus EMG activity compared to unilateral performance. PMID- 26134665 TI - Combined additive manufacturing approaches in tissue engineering. AB - Advances introduced by additive manufacturing (AM) have significantly improved the control over the microarchitecture of scaffolds for tissue engineering. This has led to the flourishing of research works addressing the optimization of AM scaffolds microarchitecture to optimally trade-off between conflicting requirements (e.g. mechanical stiffness and porosity level). A fascinating trend concerns the integration of AM with other scaffold fabrication methods (i.e. "combined" AM), leading to hybrid architectures with complementary structural features. Although this innovative approach is still at its beginning, significant results have been achieved in terms of improved biological response to the scaffold, especially targeting the regeneration of complex tissues. This review paper reports the state of the art in the field of combined AM, posing the accent on recent trends, challenges, and future perspectives. PMID- 26134666 TI - A homochiral Cu(i) coordination polymer based on achiral precursors and its photocatalytic properties. AB - A homochiral three-dimensional framework material, [Cu(7)(4-bpt)(6)(CN)(H(2)O)] (1) (4-bpt = 3,5-bis(4-pyridyl)-1,2,4-triazole), has been successfully synthesized by solvothermal reaction, which is generated through an unusual spontaneous asymmetrical crystallization from achiral precursors, and its photocatalytic properties in degradation of organic dyes are also investigated. PMID- 26134667 TI - Potential serum biomarkers of treatment response to ustekinumab in patients with psoriasis: a pilot study. PMID- 26134668 TI - The Functional Organization of Neocortical Networks Investigated in Slices with Local Field Recordings and Laser Scanning Photostimulation. AB - The organization of cortical networks can be investigated functionally in brain slices. Laser scanning photostimulation (LSPS) with glutamate-uncaging allows for a rapid survey of all connections impinging on single cells recorded in patch clamp. We sought to develop a variant of the method that would allow for a more exhaustive mapping of neuronal networks at every experiment. We found that the extracellular field recordings could be used to detect synaptic responses evoked by LSPS. One to two electrodes were placed in all six cortical layers of barrel cortex successively and maps were computed from the size of synaptic negative local field potentials. The field maps displayed a laminar organization similar to the one observed in maps computed from excitatory postsynaptic currents recorded in patch-clamp mode. Thus, LSPS combined with field recording is an interesting alternative to obtain for every animal tested a comprehensive map of the excitatory intracortical network. PMID- 26134670 TI - Theory of a microfluidic serial dilution bioreactor for growth of planktonic and biofilm populations. AB - We present the theory of a microfluidic bioreactor with a two-compartment growth chamber and periodic serial dilution. In the model, coexisting planktonic and biofilm populations exchange by adsorption and detachment. The criteria for coexistence and global extinction are determined by stability analysis of the global extinction state. Stability analysis yields the operating diagram in terms of the dilution and removal ratios, constrained by the plumbing action of the bioreactor. The special case of equal uptake function and logistic growth is analytically solved and explicit growth curves are plotted. The presented theory is applicable to generic microfluidic bioreactors with discrete growth chambers and periodic dilution at discrete time points. Therefore, the theory is expected to assist the design of microfluidic devices for investigating microbial competition and microbial biofilm growth under serial dilution conditions. PMID- 26134669 TI - Vitamin D Antagonises the Suppressive Effect of Inflammatory Cytokines on CTLA-4 Expression and Regulatory Function. AB - The immune suppressive protein CTLA-4 is constitutively expressed by Tregs and induced in effector T cells upon activation. Its crucial role in adaptive immunity is apparent from the fatal autoimmune pathology seen in CTLA-4 knockout mice. However, little is known regarding factors that regulate CTLA-4 expression and their effect upon its function to remove CD80 and CD86 from antigen presenting cells by transendocytosis. Th17 cells are emerging as significant players in autoimmunity as well as other diseases. Therefore, in this study we have examined the effects of Th17 polarising conditions on CTLA-4 expression and function in human T cells and show that Th17 conditions can suppress the expression of CTLA-4 and its transendocytic function. In contrast to Th17 cells, vitamin D is inversely associated with autoimmune disease. We have previously shown a striking ability of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) to enhance CTLA-4, however, its effects upon B7 transendocytosis and its activity in the context of inflammation remained unknown. Here we show that induction of CTLA-4 by 1,25(OH)2D3 can actually be enhanced in the presence of Th17 polarising cytokines. Furthermore, its transendocytic function was maintained such that T cells generated in the presence of Th17 conditions and 1,25(OH)2D3 were highly effective at capturing CTLA-4 ligands from antigen presenting cells and suppressing T cell division. Taken together, these data reveal an inhibitory effect of Th17 polarising conditions upon CTLA-4-mediated regulation and show that 1,25(OH)2D3 counteracts this effect. Given the importance of CTLA-4-mediated suppression in the control of autoimmune diseases, our novel data highlight the importance of vitamin D in inflammatory settings. PMID- 26134671 TI - Changes in Women's Facial Skin Color over the Ovulatory Cycle are Not Detectable by the Human Visual System. AB - Human ovulation is not advertised, as it is in several primate species, by conspicuous sexual swellings. However, there is increasing evidence that the attractiveness of women's body odor, voice, and facial appearance peak during the fertile phase of their ovulatory cycle. Cycle effects on facial attractiveness may be underpinned by changes in facial skin color, but it is not clear if skin color varies cyclically in humans or if any changes are detectable. To test these questions we photographed women daily for at least one cycle. Changes in facial skin redness and luminance were then quantified by mapping the digital images to human long, medium, and shortwave visual receptors. We find cyclic variation in skin redness, but not luminance. Redness decreases rapidly after menstrual onset, increases in the days before ovulation, and remains high through the luteal phase. However, we also show that this variation is unlikely to be detectable by the human visual system. We conclude that changes in skin color are not responsible for the effects of the ovulatory cycle on women's attractiveness. PMID- 26134672 TI - High resolution physical mapping of single gene fragments on pachytene chromosome 4 and 7 of Rosa. AB - BACKGROUND: Rosaceae is a family containing many economically important fruit and ornamental species. Although fluorescence in situ hybridization (FISH)-based physical mapping of plant genomes is a valuable tool for map-based cloning, comparative genomics and evolutionary studies, no studies using high resolution physical mapping have been performed in this family. Previously we proved that physical mapping of single-copy genes as small as 1.1 kb is possible on mitotic metaphase chromosomes of Rosa wichurana using Tyramide-FISH. In this study we aimed to further improve the physical map of Rosa wichurana by applying high resolution FISH to pachytene chromosomes. RESULTS: Using high resolution Tyramide FISH and multicolor Tyramide-FISH, 7 genes (1.7-3 kb) were successfully mapped on pachytene chromosomes 4 and 7 of Rosa wichurana. Additionally, by using multicolor Tyramide-FISH three closely located genes were simultaneously visualized on chromosome 7. A detailed map of heterochromatine/euchromatine patterns of chromosome 4 and 7 was developed with indication of the physical position of these 7 genes. Comparison of the gene order between Rosa wichurana and Fragaria vesca revealed a poor collinearity for chromosome 7, but a perfect collinearity for chromosome 4. CONCLUSIONS: High resolution physical mapping of short probes on pachytene chromosomes of Rosa wichurana was successfully performed for the first time. Application of Tyramide-FISH on pachytene chromosomes allowed the mapping resolution to be increased up to 20 times compared to mitotic metaphase chromosomes. High resolution Tyramide-FISH and multicolor Tyramide-FISH might become useful tools for further physical mapping of single-copy genes and for the integration of physical and genetic maps of Rosa wichurana and other members of the Rosaceae. PMID- 26134673 TI - The Intra- and Inter-Rater Reliability of an Instrumented Spasticity Assessment in Children with Cerebral Palsy. AB - AIM: Despite the impact of spasticity, there is a lack of objective, clinically reliable and valid tools for its assessment. This study aims to evaluate the reliability of various performance- and spasticity-related parameters collected with a manually controlled instrumented spasticity assessment in four lower limb muscles in children with cerebral palsy (CP). METHOD: The lateral gastrocnemius, medial hamstrings, rectus femoris and hip adductors of 12 children with spastic CP (12.8 years, +/-4.13 years, bilateral/unilateral involvement n=7/5) were passively stretched in the sagittal plane at incremental velocities. Muscle activity, joint motion, and torque were synchronously recorded using electromyography, inertial sensors, and a force/torque load-cell. Reliability was assessed on three levels: (1) intra- and (2) inter-rater within session, and (3) intra-rater between session. RESULTS: Parameters were found to be reliable in all three analyses, with 90% containing intra-class correlation coefficients >0.6, and 70% of standard error of measurement values <20% of the mean values. The most reliable analysis was intra-rater within session, followed by intra-rater between session, and then inter-rater within session. The Adds evaluation had a slightly lower level of reliability than that of the other muscles. CONCLUSIONS: Limited intrinsic/extrinsic errors were introduced by repeated stretch repetitions. The parameters were more reliable when the same rater, rather than different raters performed the evaluation. Standardisation and training should be further improved to reduce extrinsic error when different raters perform the measurement. Errors were also muscle specific, or related to the measurement set-up. They need to be accounted for, in particular when assessing pre-post interventions or longitudinal follow-up. The parameters of the instrumented spasticity assessment demonstrate a wide range of applications for both research and clinical environments in the quantification of spasticity. PMID- 26134674 TI - Delineating the dynamic uptake and toxicity of Ni and Co mixtures in Enchytraeus crypticus using a WHAM-FTOX approach. AB - Uptake and toxicity of Ni, Co and their mixtures in Enchytraeus crypticus after different exposure times (4, 7, 10 and 14d) were predicted using the WHAM-FTOX model, which incorporates the effects of metal speciation, affinity and competition of metals for binding sites. The combined toxicity of metals was quantified by the toxicity function (FTOX), a linear combination of the amount of metal binding to non-specific ligand sites (vi) and a toxicity coefficient (alphai). Observed body concentrations of Ni and Co in the animals correlated well with the WHAM-calculated amounts binding to humic acid, supporting the use of humic acid as a surrogate for metal binding sites of E. crypticus. The toxicity of metals at different exposure times was well predicted by the WHAM FTOX model. The derived alphaNi increased with time and reached equilibrium after approximately 14d, while alphaCo remained almost independent of time. This suggests for Ni more time is needed than for Co to reach equilibrium of body concentrations, so the toxicity of Ni is much more time-dependent. The WHAM-FTOX model provides a new tool for evaluating the potential mixture toxicity of metals to soil organisms in a dynamic environment. However, as alphai varied with exposure time, caution is warranted when using the parameters estimated from acute toxicity experiments for predicting the chronic toxicity of metal mixtures. PMID- 26134675 TI - Migration of nonylphenol from food-grade plastic is toxic to the coral reef fish species Pseudochromis fridmani. AB - Nonylphenol (NP) is a non-ionic surfactant used extensively in industrial applications, personal care products, and many plastics. We exposed marine orchid dottybacks (Pseudochromis fridmani) for 48h to either glass, Teflon, or two bags labeled as FDA food-grade polyethylene (PE1 and PE2) from different manufacturers. The PE2 bags leached high levels of NP into the contact water, which were taken up by the fish, and decreased short and long-term survival. Concentrations of NP that leached from the bags were consistent with 96h LC50 values determined in this study, indicating NP is the likely toxic agent. Despite being similarly labeled, the NP concentrations that leached from the bags and the resultant toxicity to the fish varied dramatically between manufacturers. This study highlights that some plastics, labeled as food-safe, can be highly toxic to aquatic animals, and could pose a greater threat to humans than previously realized. This study also highlights risks for aquatic animals exposed to increasing quantities of plastic waste. PMID- 26134676 TI - Biomarker analysis of combined oxytetracycline and zinc pollution in earthworms (Eisenia fetida). AB - To determine the interactive action of antibiotics and heavy metals, this study assessed pollutant-induced responses of cellular biomarkers in earthworms (Eisenia fetida) exposed to zinc (Zn(2+)) and oxytetracycline (OTC) in soil. Lysosomal membranes were damaged and coelomocyte apoptosis occurred with exposure to the individual and combined pollutants. Compared with Zn(2+) alone, lysosomal membrane stability and coelomocyte apoptosis decreased in the Zn(2+)-OTC combined treatment, possibly as a result of complexation of Zn(2+) and OTC at alkaline pH. Such complexation could reduce the toxicity of the pollutants. Lysosomal membrane stability and coelomocyte apoptosis are sensitive biomarkers and could be economical and rapid tools for the monitoring and assessment of a variety of pollutants. PMID- 26134677 TI - Targeting Notch signaling by gamma-secretase inhibitor I enhances the cytotoxic effect of 5-FU in gastric cancer. AB - Current medication for gastric cancer patients has a low success rate and the patients develop rapid tolerance to these drugs. Therefore, the development of new regimens is desired. In this study, we determined that Notch-signaling related genes were overexpressed and activated in gastric cancer patients and gastric cancer cell lines. According to recent studies, gamma-secretase inhibitors (GSIs), which function as Notch signaling inhibitors, could be used as therapeutic drugs in cancer. We demonstrated that GSI I (cbz-IL-CHO) is the most effective GSI in gastric cancer cells. We also determined the cell survival signaling-related proteins that were affected by GSI I. The levels of phosphorylated AKT were significantly decreased upon GSI I treatment, and constitutively activated myristoylated AKT completely blocked GSI I-induced apoptosis and cell survival, suggesting that inhibition of AKT signaling is critical for GSI I-mediated effects in gastric cancer cells. In order to maximize the effects and safety of GSI I, a combination treatment with GSI I and 5-FU was performed. Inhibition of gastric cancer cell proliferation with the combination treatment was significantly better than that with the single treatment. All phosphorylated forms of AKT, p44/42, JNK, and p38 were drastically changed by the combination treatment. Orthotopically transplanted gastric tumor burdens in mice were reduced using the combined treatment. The outcomes of this study clearly demonstrated the therapeutic potential of GSI I in gastric cancer, as well as the greater efficacy of the combined treatment of GSI I with 5-FU. Therefore, we suggest that further clinical trials examining the potential of combined GSI I and 5-FU treatment in gastric cancer patients be undertaken. PMID- 26134678 TI - Aurora-A-Dependent Control of TACC3 Influences the Rate of Mitotic Spindle Assembly. AB - The essential mammalian gene TACC3 is frequently mutated and amplified in cancers and its fusion products exhibit oncogenic activity in glioblastomas. TACC3 functions in mitotic spindle assembly and chromosome segregation. In particular, phosphorylation on S558 by the mitotic kinase, Aurora-A, promotes spindle recruitment of TACC3 and triggers the formation of a complex with ch-TOG-clathrin that crosslinks and stabilises kinetochore microtubules. Here we map the Aurora-A binding interface in TACC3 and show that TACC3 potently activates Aurora-A through a domain centered on F525. Vertebrate cells carrying homozygous F525A mutation in the endogenous TACC3 loci exhibit defects in TACC3 function, namely perturbed localization, reduced phosphorylation and weakened interaction with clathrin. The most striking feature of the F525A cells however is a marked shortening of mitosis, at least in part due to rapid spindle assembly. F525A cells do not exhibit chromosome missegregation, indicating that they undergo fast yet apparently faithful mitosis. By contrast, mutating the phosphorylation site S558 to alanine in TACC3 causes aneuploidy without a significant change in mitotic duration. Our work has therefore defined a regulatory role for the Aurora A-TACC3 interaction beyond the act of phosphorylation at S558. We propose that the regulatory relationship between Aurora-A and TACC3 enables the transition from the microtubule-polymerase activity of TACC3-ch-TOG to the microtubule crosslinking activity of TACC3-ch-TOG-clathrin complexes as mitosis progresses. Aurora-A-dependent control of TACC3 could determine the balance between these activities, thereby influencing not only spindle length and stability but also the speed of spindle formation with vital consequences for chromosome alignment and segregation. PMID- 26134680 TI - The achaete-scute complex in Diptera: patterns of noncoding sequence evolution. AB - The achaete-scute complex (AS-C) has been a useful paradigm for the study of pattern formation and its evolution. achaete-scute genes have duplicated and evolved distinct expression patterns during the evolution of cyclorraphous Diptera. Are the expression patterns in different species driven by conserved regulatory elements? If so, when did such regulatory elements arise? Here, we have sequenced most of the AS-C of the fly Calliphora vicina (including the genes achaete, scute and lethal of scute) to compare noncoding sequences with known cis regulatory sequences in Drosophila. The organization of the complex is conserved with respect to Drosophila species. There are numerous small stretches of conserved noncoding sequence that, in spite of high sequence turnover, display binding sites for known transcription factors. Synteny of the blocks of conserved noncoding sequences is maintained suggesting not only conservation of the position of regulatory elements but also an origin prior to the divergence between these two species. We propose that some of these enhancers originated by duplication with their target genes. PMID- 26134681 TI - Alkaline biodegradable implants for osteoporotic bone defects--importance of microenvironment pH. AB - Change of microenvironment pH by biodegradable implants may ameliorate unbalanced osteoporotic bone remodeling. The present work demonstrated that a weak alkaline condition stimulated osteoblasts differentiation while suppressed osteoclast generation. In vivo, implants with an alkaline microenvironment pH (monitored by a pH microelectrode) exhibited a promising healing effect for the repair of osteoporotic bone defects. INTRODUCTION: Under osteoporotic conditions, the response of the bone microenvironment to an endosseous implant is significantly impaired, and this substantially increases the risk of fracture, non-union and aseptic implant loosening. Acid-base equilibrium is an important factor influencing bone cell behaviour. The present purpose was to study the effect of a series of alkaline biodegradable implant materials on regeneration of osteoporotic bone defect, monitoring the microenvironment pH (MUe-pH) over time. METHODS: The proliferation and differentiation potential of osteoporotic rat bone marrow stromal cells and RAW 264.7 cells were examined under various pH conditions. Ovariectomized rat bone defects were filled with specific biodegradable materials, and MUe-pH was measured by pH microelectrode. New osteoid and tartrate-resistant acid phosphatase-positive osteoclast-like cells were examined by Goldner's trichrome and TRAP staining, respectively. The intermediate layer between implants and new bone were studied using energy dispersive X-ray spectroscopy (EDX) linear scanning. RESULTS: In vitro, weak alkaline conditions stimulated osteoporotic rat bone marrow stromal cells (oBMSC) differentiation, while inhibiting the formation of osteoclasts. In vivo, MUe-pH differs from that of the homogeneous peripheral blood and exhibits variations over time particular to each material. Higher initial MUe-pH was associated with more new bone formation, late response of TRAP-positive osteoclast-like cells and the development of an intermediate 'apatitic' layer in vivo. EDX suggested that residual material may influence MUe-pH even 9 weeks post-surgery. CONCLUSION: The pH microelectrode is suitable for in vivo MUe-pH detection. Alkaline biodegradable materials generate an in vivo microenvironmental pH which is higher than the normal physiological value and show promising healing effects in the context of osteoporotic bone defects. PMID- 26134682 TI - Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults. AB - Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. INTRODUCTION: This study aims to assess 25-hydroxyvitamin D-25(OH)D-status in Spanish adult subjects and to analyze its relationships with serum PTH levels, calcium intake, and bone mineral density (BMD). METHODS: A total of 1811 individuals (1154 postmenopausal women and 657 men) aged 44-93 years participated in the study. Serum 25(OH)D, intact parathyroid hormone (PTH), aminoterminal propeptide of type I collagen (P1NP), and C-terminal telopeptide of type I collagen (beta-CTX) levels were measured by electrochemiluminescence. BMD was determined by dual x-ray absorptiometry (DXA) at lumbar spine, femoral neck, and total hip. RESULTS: Serum 25(OH)D levels were below 10, 20, and 30 ng/ml in 5, 40, and 83 % of participants, respectively. There was a significant seasonal difference in mean serum 25(OH)D, with higher levels in summer-autumn. In multivariate analysis, 25(OH)D levels were negatively correlated with age, serum PTH and creatinine, body mass index, smoking, alcohol intake, and a number of chronic diseases, but positively with dairy calcium intake. The magnitude of the difference in serum PTH according to 25(OH)D quartiles was not influenced by calcium intake. A threshold of serum 25(OH)D around 30 ng/ml was observed for serum PTH and hip BMD. CONCLUSIONS: Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. Programs to improve vitamin D status may be required in our country. PMID- 26134683 TI - Overdiagnosis of osteoporosis: fact or fallacy? PMID- 26134684 TI - Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer. AB - PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of the present study was to clarify the significance of PTPRH expression and its regulation by DNA methylation in non small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LADC). PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort that consisted of 145 patients with LADC, a major NSCLC subtype. Gene regulation by DNA methylation was assessed using a DNA methylation inhibitor. PTPRH mRNA expression was significantly upregulated in NSCLC. PTPRH DNA methylation was reduced in LADC samples and inversely correlated with mRNA expression. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines with low PTPRH expression, restored mRNA PTPRH expression levels. Furthermore, low PTPRH methylation was associated with shorter recurrence-free survival (P=1.64x10(-4)) and overall survival (P=5.54x10(-5)). Multivariate analysis revealed that PTPRH DNA methylation was an independent prognostic factor (P=6.88x10(-3)). It was confirmed that PTPRH is overexpressed in NSCLC. Furthermore, we determined that PTPRH is epigenetically regulated by DNA hypomethylation, with prognostic implications for LADC. PMID- 26134685 TI - Blindness alters the microstructure of the ventral but not the dorsal visual stream. AB - Visual deprivation from birth leads to reorganisation of the brain through cross modal plasticity. Although there is a general agreement that the primary afferent visual pathways are altered in congenitally blind individuals, our knowledge about microstructural changes within the higher-order visual streams, and how this is affected by onset of blindness, remains scant. We used diffusion tensor imaging and tractography to investigate microstructural features in the dorsal (superior longitudinal fasciculus) and ventral (inferior longitudinal and inferior fronto-occipital fasciculi) visual pathways in 12 congenitally blind, 15 late blind and 15 normal sighted controls. We also studied six prematurely born individuals with normal vision to control for the effects of prematurity on brain connectivity. Our data revealed a reduction in fractional anisotropy in the ventral but not the dorsal visual stream for both congenitally and late blind individuals. Prematurely born individuals, with normal vision, did not differ from normal sighted controls, born at term. Our data suggest that although the visual streams are structurally developing without normal visual input from the eyes, blindness selectively affects the microstructure of the ventral visual stream regardless of the time of onset. We suggest that the decreased fractional anisotropy of the ventral stream in the two groups of blind subjects is the combined result of both degenerative and cross-modal compensatory processes, affecting normal white matter development. PMID- 26134686 TI - Judging journals' impact. PMID- 26134687 TI - Diverging global trends in heart disease and diabetes: implications for dietary guidelines. PMID- 26134688 TI - Diverging global trends in heart disease and type 2 diabetes: the role of carbohydrates and saturated fats. PMID- 26134689 TI - Highly Sensitive CO2-Responsive Polymeric Microgels That Respond Within Seconds. AB - In this work, polymeric microgels with swift response to CO2 are synthesized by polymerization of tertiary-amine containing methacrylate monomers (N,N diethylaminoethyl methacrylate, DEAEMA) and polyethylene glycol monomethyl ether acrylate (PEGMA) as stabilizers. The obtained microgels are stable but very sensitive to CO2, which can rapidly swell and further collapse within 5 s upon bubbling of CO2, or within minutes in an atmosphere of gaseous CO2. The protonation of the tertiary amine groups in the presence of CO2 induces sensitive swelling and further irreversible collapse of the microgels due to the internal charge repulsion and relatively low cross-linking density in the core area of microgels. This rapid response to CO2 may find further applications in the fields of sensitive detection or responsive loading and release upon CO2 stimulus. PMID- 26134690 TI - Short- and Long-Term Influence of Fluoride-Containing Prophylactics on the Growth of Streptococcus mutans on Titanium Surface. AB - OBJECTIVES: Acidic pH and high fluoride (F(-)) concentration impair the corrosion resistance of titanium (Ti). Caries-preventive products contain high amounts of F(-) and are applied at low pH. The purpose of this study was to evaluate whether fluoride applied in different forms has different short-, mid-, and long-term effects on the growth of the bacteria Streptococcus mutans. MATERIALS AND METHODS: Ti discs with polished surface were treated with a rinse containing 0.025% olaflur, a gel containing 1.25% olaflur, or a 1% aqueous solution of NaF (pH 4.5), and they were incubated with S mutans for 21 days. Control discs did not get prophylactic treatment. Protein assay analysis was performed at regular intervals to estimate the amount of S mutans. Scanning electron microscopic (SEM) images were also taken. RESULTS: Bacterial protein quantity became significantly different only by the 21st day. Fluoride in rinse and gel proved to be superior to NaF in aqueous solution or no treatment (P < 0.01 and P < 0.05, respectively). However, the discs treated with fluoride in gel showed signs of corrosion in SEM images. CONCLUSION: The results suggest that the use of fluoride-containing mouthwashes might be the best and safest oral hygienic choice for patients with oral implants. Furthermore, olaflur seems to be superior to NaF for long-term use at low pH. PMID- 26134692 TI - The rise and rise of advanced practice nursing. PMID- 26134694 TI - Decompressive hemicraniectomy in the management of extensive middle cerebral artery stroke: increased survival, at a price. PMID- 26134695 TI - Oral chronic graft-versus-host disease in Australia: clinical features and challenges in management. AB - Data from the Australasian Bone Marrow Transplant Recipient Registry show a steady increase in the number of allogeneic haemopoietic stem cell transplantations (HSCT) performed annually in Australia and New Zealand. In 2012, 629 allogeneic HSCT were performed. Allogeneic HSCT is associated with numerous potential complications, including chronic graft-versus-host disease (cGVHD). The oral cavity is one of the most frequent sites affected by cGvHD, often leading to significant disability and reduced quality of life. Management strategies are often complex, of variable efficacy and influenced by the availability of various therapeutic agents, access to compounding pharmacies and associated costs. This paper summarises the current status of allogeneic HSCT in Australia and New Zealand with a focus on oral cGvHD and the associated challenges in its management. PMID- 26134696 TI - The art of prescribing: negotiating the decision of generic or branded medications. AB - Prescribing choices between generic and branded medications are not without consequence, and these decisions require careful consideration as these may potentially lead to patient confusion, medication errors and adverse events. Understanding our prescribing decisions may allow for greater patient autonomy and involvement, and potentially minimise medication-related harms. PMID- 26134697 TI - Glycogenic hepatopathy is an under-recognised cause of hepatomegaly and elevated liver transaminases in type 1 diabetes mellitus. AB - Glycogenic hepatopathy (GH) is an under-recognised complication of type 1 diabetes mellitus (T1DM) not controlled to target resulting in hepatomegaly and elevated liver transaminases. We report the case of a 19-year-old man with T1DM not controlled to target who presented with abdominal pain, hepatomegaly and deranged liver transaminases. He was subsequently diagnosed with GH on liver biopsy, with the mainstay of treatment being reduction in caloric intake and insulin. PMID- 26134698 TI - Experience of morning reports in the emergency department. AB - Morning report in the emergency medicine departments is an emerging teaching modality in the medicine curriculum. Our institution, Hotel-Dieu de France hospital, a multidisciplinary tertiary care university hospital affiliated to the Saint Joseph University of Medical Sciences, is the only hospital in Middle East to hold morning reports in the emergency department (ED). We evaluate the usefulness of the morning report as a pedagogic tool as it assesses the content, quality of the discussions, professionalism, leadership, participation and duration of the morning report. The particularity of this paper is that it takes into consideration the interns' input often under-recognised in the studies. An anonymous questionnaire was diffused to the residents and interns that rotated in the ED during the previous year. It consisted of seven multiple-choice questions to evaluate the quality of the presentations, targeted discussions, ethics and professionalism, evidence-based medicine, clinical reasoning, relation of cases to discussions and implication of the ED physician. Overall, of the 63 patients who answered the survey, 65.1% were satisfied by the content. The majority considered the quality of the discussions acceptable and the leadership and participation satisfactory, professionalism was judged poor. Both residents and interns were satisfied of the teaching point of the morning reports. The only fail back observed was professionalism and pathophysiological discussions that require to be added to the sessions, whereas clinical management, teaching points, leadership and time management were completely satisfactory. PMID- 26134699 TI - Granulomatous hepatitis with hepatic mass lesions and a response to infliximab. PMID- 26134700 TI - A near miss! Severe multivessel coronary artery spasm. PMID- 26134701 TI - A case of immunoglobulin G4 (IgG4) tubulointerstitial nephritis with delayed elevation of serum IgG4 levels. PMID- 26134702 TI - The neglected aspects of dementia care. PMID- 26134703 TI - Best practice aminoglycoside monitoring. PMID- 26134704 TI - Author reply: To PMID 25367725. PMID- 26134705 TI - AVP-NPII gene mutations and clinical characteristics of the patients with autosomal dominant familial central diabetes insipidus. AB - BACKGROUND: Familial central diabetes insipidus (DI), usually an autosomal dominant disorder, is caused by mutations in arginine vasopressin-neurophysin II (AVP-NPII) gene that leads to aberrant preprohormone processing and gradual destruction of AVP-secreting cells. OBJECTIVE: To determine clinical and molecular characteristics of patients with familial central DI from two different Turkish families. MATERIALS AND METHODS: The diagnosis of central DI was established by 24-h urine collection, water deprivation test, and desmopressin challenge. To confirm the diagnosis of familial central DI, the entire coding region of AVP-NPII gene was amplified and sequenced. A total of eight affected patients and three unaffected healthy relatives from two families were studied. RESULTS: Genetic analysis revealed a previously reported heterozygous mutation (p.C98X) in family A, and a heterozygous novel mutation (p.G45C) in family B, both detected in exon 2 of AVP-NPII gene. When we compared the clinical characteristics of the two families, it was noticed that as the age of onset of symptoms in family A ranges between 4 and 7 years, it was <1 year in family B. Additionally, pituitary bright spot was present in the affected siblings, but absent in their affected parents. CONCLUSION: Familial central DI is a progressive disease, and age of onset of symptoms can differ depending on the mutation. Bright spot on pituitary MRI might be present at onset, but become invisible over time. Genetic testing and appropriate counseling should be given in familial cases of central DI to ensure adequate treatment, and to avoid chronic water deprivation that might result in growth retardation in childhood. PMID- 26134706 TI - Quantitative comparison of the microscopic anatomy of the human ACL femoral and tibial entheses. AB - The femoral enthesis of the human anterior cruciate ligament (ACL) is known to be more susceptible to injury than the tibial enthesis. To determine whether anatomic differences might help explain this difference, we quantified the microscopic appearance of both entheses in 15 unembalmed knee specimens using light microscopy, toluidine blue stain and image analysis. The amount of calcified fibrocartilage and uncalcified fibrocartilage, and the ligament entheseal attachment angle were then compared between the femoral and tibial entheses via linear mixed-effects models. The results showed marked differences in anatomy between the two entheses. The femoral enthesis exhibited a 3.9-fold more acute ligament attachment angle than the tibial enthesis (p<0.001), a 43% greater calcified fibrocartilage tissue area (p<0.001), and a 226% greater uncalcified fibrocartilage depth (p<0.001), with the latter differences being particularly pronounced in the central region. We conclude that the ACL femoral enthesis has more fibrocartilage and a more acute ligament attachment angle than the tibial enthesis, which provides insight into why it is more vulnerable to failure. PMID- 26134707 TI - Genome-wide investigation and expression analysis of Sodium/Calcium exchanger gene family in rice and Arabidopsis. AB - BACKGROUND: The Na(+)/Ca(2+) Exchanger (NCX) protein family is a member of the Cation/Ca(2+) exchanger superfamily and its members play important roles in cellular Ca(2+) homeostasis. While the functions of NCX family of proteins is well understood in humans, not much is known about the total complement of Na(+)/Ca(2+) exchangers in plants and their role in various physiological and developmental processes. In the present study, we have identified all the NCX proteins encoded in the genomes of rice and Arabidopsis and studied their phylogeny, domain architecture and expression profiles across different tissues, at various developmental stages and under stress conditions. RESULTS: Through whole genome investigation, we identified twenty-two NCX proteins encoded by fifteen genes in rice and sixteen NCX proteins encoded by thirteen genes in Arabidopsis. Based on phylogenetic reconstruction, these could be classified into five clades, members of most of which were found to possess distinct domain architecture. Expression profiling of the identified NCX genes using publicly available MPSS and microarray data showed differential expression patterns under abiotic stresses, and at various development stages. In rice, OsNCX1, OsNCX8, OsNCX9 and OsNCX15 were found to be highly expressed in all the plant parts and various developmental stages. qRT-PCR based expression analysis revealed that OsNCX3, OsNCX10 and OsNCX15 were highly induced by salt and dehydration stress. Besides, expression profiling showed differential regulation of rice NCX genes in response to calcium and EGTA. Interestingly, expression of none of the NCX genes was found to be co-regulated by NaCl and calcium. CONCLUSIONS: Together, our results present insights into the potential role of NCX family of proteins in abiotic stresses and development. Findings of the present investigation should serve as a starting point for future studies aiming functional characterization of plant NCX family proteins. PMID- 26134708 TI - Improving fold activation of small transcription activating RNAs (STARs) with rational RNA engineering strategies. AB - Regulatory RNAs have become integral components of the synthetic biology and bioengineering toolbox for controlling gene expression. We recently expanded this toolbox by creating small transcription activating RNAs (STARs) that act by disrupting the formation of a target transcriptional terminator hairpin placed upstream of a gene. While STARs are a promising addition to the repertoire of RNA regulators, much work remains to be done to optimize the fold activation of these systems. Here we apply rational RNA engineering strategies to improve the fold activation of two STAR regulators. We demonstrate that a combination of promoter strength tuning and multiple RNA engineering strategies can improve fold activation from 5.4-fold to 13.4-fold for a STAR regulator derived from the pbuE riboswitch terminator. We then validate the generality of our approach and show that these same strategies improve fold activation from 2.1-fold to 14.6-fold for an unrelated STAR regulator, opening the door to creating a range of additional STARs to use in a broad array of biotechnologies. We also establish that the optimizations preserve the orthogonality of these STARs between themselves and a set of RNA transcriptional repressors, enabling these optimized STARs to be used in sophisticated circuits. PMID- 26134709 TI - Glycosyldiselenides as lectin ligands detectable by NMR in biofluids. AB - The ability of glycosyldiselenides to act as lectin ligands and their selective detection in plasma by (77)Se NMR is reported. PMID- 26134710 TI - Prosecuting Intimate Partner Sexual Assault: Legal and Extra-Legal Factors That Influence Charging Decisions. AB - Prosecutors play a crucial role in determining whether persons who are accused of intimate partner sexual assault (IPSA) will be sanctioned by the criminal justice system. Prosecutors have unconditional discretion at the initial charging stage because a case rejection decision is typically immune to review. Using qualitative data from 47 IPSA complaints that were referred to Los Angeles County or City prosecution in 2008, this study examines the factors that influence charging decisions. Findings suggest that prosecutors consider both legal and extralegal factors when making charging decisions and that various cultural, legal, and rape myths surrounding IPSA influence these decisions. PMID- 26134711 TI - To Tell or Not to Tell. AB - The underreporting of rape is well known; however, there is less information on women who fail to disclose to anyone. This online study suggests that 24% of 242 women who were non-disclosing compared with those who had disclosed were significantly less likely to seek treatment for emotional injuries. Also, almost two thirds of non-disclosing women believed that the abuse was their fault versus 39.1% of women with prior disclosure. Of clinical interest is that regardless of disclosure pattern, there was no significant difference in reports of depression, anxiety, or posttraumatic stress disorder (PTSD), and the majority of respondents endorsed support for online counseling over telephone or individual contact. PMID- 26134712 TI - Paramagnetic Prussian Blue Analogues CsM(II)[M(III)(CN)6]. The Quest for Spin on Cesium Ions by Use of (133)Cs MAS NMR Spectroscopy. AB - The (133)Cs magic-angle spinning NMR spectra of the paramagnetic compounds CsM(II)[M(III)(CN)6], M(II) = Ni, Co, Fe, Mn; M(II) = Co, Fe, yield unusually large and temperature-dependent signal shifts (up to -950 ppm relative to CsCl at 298 K). Comparison with the spectra of the diamagnetic analogues CsM[Co(CN)6], M = Zn, Cd, shows that the shifts are largely due to the unpaired electrons. This is ascribed to through-bond transfer of spin to the Cs(+) ions, while the through space effect of the magnetic moments on the signal shifts is shown to be virtually negligible. The mechanism inducing negative spin at Cs(+) is discussed. The magnitude of the spin density (average: |5.8 * 10(-3)| (a.u.) (-3)) suggests that Cs(+) is involved in magnetic exchange interactions of corresponding Prussian blue derivatives. PMID- 26134713 TI - A technique for correction of attenuations in synchronous fluorescence spectroscopy. AB - Synchronous fluorescence spectroscopy is an efficient technique for decoupling fluorophores which are masked in fluorescence spectroscopy due to overlapping of dominant fluorophores. By choosing appropriate offsets between excitation and emission wavelengths during signal acquisition from turbid samples, responses of individual fluorophores are highlighted as sharp peaks by using this technique. Some of the peaks may, however, still be missed due to wavelength dependent absorption and scattering effects. In this study a correction technique is used to extract such hidden signatures. The technique is validated using tissue phantoms with known concentrations of fluorophores, absorbers and scatterers. On the basis of validation studies on single and combination of two fluorophores, it is found that lower offsets display better recovery due to minimal influence of absorption by blood. Among the different offsets, 55 nm is found to be optimal for investigation of cervical precancers. PMID- 26134714 TI - Stem Cell Transplant in Severe Glanzmann Thrombasthenia in an Adult Patient. AB - Glanzmann thrombasthenia is an inherited auto-somal recessive disorder characterized by normal platelet count but lack of platelet aggregation due to absence of platelet glycoprotein IIb/IIIa. The disease usually is associated with mild bleeding, but severe fatal hemorrhage may occur. Allogeneic stem cell transplant is the only curative method of treatment. A literature search showed 18 previously reported cases of Glanzmann thrombasthenia treated with allogeneic hematopoietic stem cell transplant. We report an 18-year-old woman with severe Glanzmann thrombasthenia who was treated with allogeneic hematopoietic stem cell transplant from her sister. After 24-month follow-up, the patient was well, had no bleeding tendency, and had mild chronic skin graft-versus-host disease. PMID- 26134715 TI - Translational applications of molecular imaging in cardiovascular disease and stem cell therapy. AB - Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Molecular imaging techniques provide valuable information at cellular and molecular level, as opposed to anatomical and structural layers acquired from traditional imaging modalities. More specifically, molecular imaging employs imaging probes which interact with specific molecular targets and therefore makes it possible to visualize biological processes in vivo. Molecular imaging technology is now progressing towards preclinical and clinical application that gives an integral and comprehensive guidance for the investigation of cardiovascular disease. In addition, cardiac stem cell therapy holds great promise for clinical translation. Undoubtedly, combining stem cell therapy with molecular imaging technology will bring a broad prospect for the study and treatment of cardiac disease. This review will focus on the progresses of molecular imaging strategies in cardiovascular disease and cardiac stem cell therapy. Furthermore, the perspective on the future role of molecular imaging in clinical translation and potential strategies in defining safety and efficacy of cardiac stem cell therapies will be discussed. PMID- 26134716 TI - Differences in activity of actinoporins are related with the hydrophobicity of their N-terminus. AB - Actinoporins are pore-forming toxins (PFT) produced by sea anemones with molecular mass around 20 kDa and high affinity for sphingomyelin. The most studied atinoporins are sticholysins I and II (StI/StII) from Stichodactyla helianthus, equinatoxin II (EqtII) from Actinia equina, and fragaceatoxin C (FraC) from Actinia fragacea. Their N-terminal sequences encompassing residues 1 30 seem to be the best candidates for pore formation. This segment comprises an amphipathic alpha-helix preceded by a more or less hydrophobic segment, depending on the toxin, of around 10 amino acid residues. Although it is clear that the N terminal is the most variable sequence in this protein family, the role of their hydrophobic segment in not fully understood. Here we show a comparison of StI, StII, EqtII, and FraC activities with that of their respective N-terminal synthetic peptides. The hemolytic and permeabilizing activity of the peptides reproduce qualitatively the behavior of their respective parental proteins and are particularly related to the hydrophobicity of the corresponding 1-10 segment. Furthermore, the dendrogram analysis of actinoporins' N-terminal sequence allows relating differences in alignment with differences in activity among the four toxins. We have also evaluated the penetration depth of the N-terminal segment of StI and StII by using Trp-containing peptide-analogs. Our data suggest that the N terminus of StII is more deeply buried into the hydrophobic core of the bilayer than that of StI. We hypothesize that the highest activity of StII could be ascribed to a larger hydrophobic continuum, an uninterrupted sequence of non charged mainly hydrophobic amino acid residues, of its N-terminus promoting a highest ability to partially insert in the membrane core. Moreover, as we show for four related peptides that a higher hydrophobicity contributes to increase the activity, we reinforce the notion that this property must be taken into account to design new potent membranotropic agents. PMID- 26134717 TI - The HAlF4 superacid fragmentation induced by an excess electron attachment. AB - The excess electron attachment to the HAlF4 superacid molecule was studied by employing ab initio CCSD(T) and MP2 methods and a purposely suited aug-cc pVTZ+4s4p3d basis set. The results indicate that the HAlF4 molecule, due to its polarity, may attract a distant excess electron and form a dipole-bound anionic state whose vertical electron binding energy is 1106 cm(-1). The initially formed (HAlF4)(-) anion of a dipole-bound nature undergoes an immediate structural reorganization driven by the (AlF4)(-) strongly-bound superhalogen anion formation. The potential energy surface analysis leads to the conclusion that the (HAlF4)(-) -> (AlF4)(-) + H transformation should proceed spontaneously and involve the simultaneous structure relaxation of the AlF4 moiety (in the direction approaching a tetrahedral geometry) and the excess electron density migration from the area outside the molecular framework to the valence AlF4 region. The fragmentation of the HAlF4 superacid molecule is predicted to be the final effect of the excess electron attachment process. In addition, the important antenna role of the initially formed (HAlF4)(-) dipole-bound anionic state is discussed. PMID- 26134718 TI - The Intensity of Voluntary, Induced, and Spontaneous Cough. AB - BACKGROUND: The intensity of cough is an important determinant of cough severity. Few studies have quantified cough intensity in patients with chronic cough with objective measures. We investigated the intensity of voluntary, induced, and spontaneous cough in patients with chronic cough and healthy control subjects. METHODS: Patients with chronic cough and control subjects underwent physiologic assessment of the intensity of maximum voluntary, capsaicin-induced, and spontaneous cough. Assessments included measurement of gastric pressure (Pga) and esophageal pressure (Pes) during cough, peak cough flow (PCF), expiratory muscle strength (twitch gastric pressure [TwPga]), and cough compression phase duration (CPD). Subjective perception of cough intensity was assessed using a visual analog scale (VAS). RESULTS: Pes, Pga, and PCF during maximum voluntary cough were significantly greater in patients with chronic cough compared with control subjects (P = .003-.042). There was no difference in TwPga between patients and control subjects. CPD was increased in female patients compared with control subjects (mean +/- SD, 0.50 +/- 0.22 s vs 0.28 +/- 0.17 s; P = .007). Mean +/- SD Pes during spontaneous cough was comparable to induced cough (128 +/- 28 cm H2O vs 122 +/- 37 cm H2O, P = .686) but less than maximum voluntary cough (170 +/- 46 cm H2O, P = .020). Median within-subject correlation coefficients between cough intensity VAS and Pes, Pga, and PCF were r = 0.82 to 0.86. CONCLUSIONS: Maximum voluntary cough intensity was increased in patients with chronic cough compared with control subjects. There was no significant difference in expiratory muscle contractility. Further studies should evaluate the compressive phase of cough in more detail. Physiologic measures of cough intensity correlated strongly with subjective perception of intensity in patients with chronic cough and may be relevant objective outcome measures for clinical studies. PMID- 26134719 TI - In Support of a Post-Au.D. Fellowship. PMID- 26134720 TI - Improving Hearing Performance for Cochlear Implant Recipients with Use of a Digital, Wireless, Remote-Microphone, Audio-Streaming Accessory. AB - BACKGROUND: Cochlear implant (CI) recipients experience difficulty understanding speech in noise. Remote-microphone technology that improves the signal-to-noise ratio is recognized as an effective means to improve speech recognition in noise; however, there are no published studies evaluating the potential benefits of a wireless, remote-microphone, digital, audio-streaming accessory device (heretofore referred to as a remote-microphone accessory) designed to deliver audio signals directly to a CI sound processor. PURPOSE: The objective of this study was to compare speech recognition in quiet and in noise of recipients while using their CI alone and with a remote-microphone accessory. RESEARCH DESIGN: A two-way repeated measures design was used to evaluate performance differences obtained in quiet and in increasing levels of competing noise with the CI sound processor alone and with the sound processor paired to the remote microphone accessory. STUDY SAMPLE: Sixteen users of Cochlear Nucleus 24 Freedom, CI512, and CI422 implants were included in the study. DATA COLLECTION AND ANALYSIS: Participants were evaluated in 14 conditions including use of the sound processor alone and with the remote-microphone accessory in quiet and at the following signal levels: 65 dBA speech (at the location of the participant; 85 dBA at the location of the remote microphone) in quiet and competing noise at 50, 55, 60, 65, 70, and 75 dBA noise levels. Speech recognition was evaluated in each of these conditions with one full list of AzBio sentences. RESULTS: Speech recognition in quiet and in all competing noise levels, except the 75 dBA condition, was significantly better with use of the remote-microphone accessory compared with participants' performance with the CI sound processor alone. As expected, in all technology conditions, performance was significantly poorer as the competing noise level increased. CONCLUSIONS: Use of a remote-microphone accessory designed for a CI sound processor provides superior speech recognition in quiet and in noise when compared with performance obtained with the CI sound processor alone. PMID- 26134721 TI - Comparison of Clinical and Traditional Gap Detection Tests. AB - BACKGROUND: Temporal resolution is important for speech recognition and may contribute to variability in speech recognition among patients. Clinical tests of temporal resolution are available, but it is not clear how closely results of those tests correspond to results of traditional temporal resolution tests. PURPOSE: The purpose of this study was to compare the Gaps-in-Noise (GIN) test to a traditional measure of gap detection. STUDY SAMPLE: This study included older adults with hearing loss and younger adults with normal hearing. DATA COLLECTION AND ANALYSIS: Participants completed one practice and two test blocks of each gap detection test, and a measure of speech-in-noise recognition. Individual data were correlated to examine the relationship between the tests. RESULTS: The GIN and traditional gap detection were significantly, but not highly correlated. The traditional gap detection test contributed to variance in speech recognition in noise, while the GIN did not. CONCLUSIONS: The brevity and ease of implementing the GIN in the clinic make it a viable test of temporal resolution. However, it differs from traditional measures in implementation, and as a result relies on different cognitive factors. The GIN thresholds should be interpreted carefully and not presumed to represent an approximation of traditional gap detection thresholds. PMID- 26134722 TI - The Effect of a High Upper Input Limiting Level on Word Recognition in Noise, Sound Quality Preferences, and Subjective Ratings of Real-World Performance. AB - BACKGROUND: One important factor that plays a role in front-end processing is the analog-to-digital converter within current hearing aids. The average input dynamic range of hearing aids is 96 dB SPL with an upper input limiting level (UILL) of 95-105 dB SPL. The UILL of standard hearing aids could distort loud signals, such as loud speech or music, which have root-mean-square values of 90 and 105 dB SPL with crest factors of 12 dB SPL to 14-20 dB SPL, respectively. This indicates that these loud sounds could create a distorted signal for patients when the input limiting level is reached. PURPOSE: To examine if significant differences in word recognition in noise, sound quality preferences, and subjective ratings of real-world performance exist between conventional and high UILL hearing aids. RESEARCH DESIGN: Words in noise and sound quality preferences were assessed using recordings on a Knowles Electronic Manikin for Acoustic Research with conventional and high UILL hearing aids, different microphone modes, and listening conditions. Participants wore the hearing aids for 2 mo and completed questionnaires on subjective performance. STUDY SAMPLE: Ten adults with bilateral slight to moderately severe sensorineural hearing loss were recruited. RESULTS: A four-factor repeated-measures analysis of variance (ANOVA) revealed significant differences between the conventional and high UILL across microphone modes and listening conditions for words in noise [F(2, 18) = 6.0; p < 0.05]. A three-factor repeated-measures ANOVA for sound quality preferences revealed a significant difference only for presentation level [F(1, 9) = 81.0; p < 0.001]. A one-factor ANOVA did not reveal significant differences between the conventional and high UILL on subjective ratings of real-world performance. CONCLUSIONS: Word recognition and sound quality preferences revealed significant differences between the conventional and high UILL; however, there were no differences in subjective ratings of real-world performance. One participant preferred the conventional UILL, two the high UILL, and seven thought performance was equal, which may be due to the listening environments participants encountered, as evidenced by datalogging. PMID- 26134723 TI - Measuring Temporal Resolution (Release of Masking) with a Hughson-Westlake Up Down Instead of a Bekesy-Tracking Procedure. AB - BACKGROUND: A temporal resolution test in addition to the pure-tone audiogram may be of great clinical interest because of its relevance in speech perception and expected relevance in hearing aid fitting. Larsby and Arlinger developed an appropriate clinical test, but this test uses a Bekesy-tracking procedure for estimating masked thresholds in stationary and interrupted noise to assess release of masking (RoM) for temporal resolution. Generally the Hughson-Westlake up-down procedure is used in the clinic to measure the pure-tone thresholds in quiet. A uniform approach will facilitate clinical application and might be appropriate for RoM measurements as well. Because there is no golden standard for measuring the RoM in the clinic, we examine in the present study the Hughson Westlake up-down procedure to measure the RoM and compare the results with the Bekesy-tracking procedure. PURPOSE: The purpose of the current study was to examine the differences between a Bekesy-tracking procedure and the Hughson Westlake up-down procedure for estimating masked thresholds in stationary and interrupted noise to assess RoM. RESEARCH DESIGN: RoM is assessed in eight normal hearing (NH) and ten hearing-impaired (HI) listeners through both methods. Results from both methods are compared with each other and with predicted thresholds from a model. DATA ANALYSIS: Wilcoxon signed-rank tests, paired t tests. RESULTS: Some differences between the two methods were found. We used a model to quantify the results of the two measurement procedures. The results of the Hughson-Westlake procedure were clearly better in agreement with the model than the results of the Bekesy-tracking procedure. Furthermore, the Bekesy tracking procedure showed more spread in the results of the NH listeners than the Hughson-Westlake procedure. CONCLUSIONS: The Hughson-Westlake procedure seems to be an applicable alternative for measuring RoM for temporal resolution in the clinical audiological practice. PMID- 26134724 TI - Discrimination of Stochastic Frequency Modulation by Cochlear Implant Users. AB - BACKGROUND: Past work has shown that low-rate frequency modulation (FM) may help preserve signal coherence, aid segmentation at word and syllable boundaries, and benefit speech intelligibility in the presence of a masker. PURPOSE: This study evaluated whether difficulties in speech perception by cochlear implant (CI) users relate to a deficit in the ability to discriminate among stochastic low rate patterns of FM. RESEARCH DESIGN: RESEARCH DESIGN: This is a correlational study assessing the association between the ability to discriminate stochastic patterns of low-rate FM and the intelligibility of speech in noise. STUDY SAMPLE: Thirteen postlingually deafened adult CI users participated in this study. DATA COLLECTION AND ANALYSIS: Using modulators derived from 5-Hz lowpass noise applied to a 1-kHz carrier, thresholds were measured in terms of frequency excursion both in quiet and with a speech-babble masker present, stimulus duration, and signal to-noise ratio in the presence of a speech-babble masker. Speech perception ability was assessed in the presence of the same speech-babble masker. Relationships were evaluated with Pearson product-moment correlation analysis with correction for family-wise error, and commonality analysis to determine the unique and common contributions across psychoacoustic variables to the association with speech ability. RESULTS: Significant correlations were obtained between masked speech intelligibility and three metrics of FM discrimination involving either signal-to-noise ratio or stimulus duration, with shared variance among the three measures accounting for much of the effect. Compared to past results from young normal-hearing adults and older adults with either normal hearing or a mild-to-moderate hearing loss, mean FM discrimination thresholds obtained from CI users were higher in all conditions. CONCLUSIONS: The ability to process the pattern of frequency excursions of stochastic FM may, in part, have a common basis with speech perception in noise. Discrimination of differences in the temporally distributed place coding of the stimulus could serve as this common basis for CI users. PMID- 26134726 TI - All Treatments in Tinnitus Are Experimental, Controversial, and Futuristic: A Comment on "Experimental, Controversial, and Futuristic Treatments for Chronic Tinnitus" by Folmer et al (2014). PMID- 26134725 TI - List Equivalency of PRESTO for the Evaluation of Speech Recognition. AB - BACKGROUND: There is a pressing clinical need for the development of ecologically valid and robust assessment measures of speech recognition. Perceptually Robust English Sentence Test Open-set (PRESTO) is a new high-variability sentence recognition test that is sensitive to individual differences and was designed for use with several different clinical populations. PRESTO differs from other sentence recognition tests because the target sentences differ in talker, gender, and regional dialect. Increasing interest in using PRESTO as a clinical test of spoken word recognition dictates the need to establish equivalence across test lists. PURPOSE: The purpose of this study was to establish list equivalency of PRESTO for clinical use. RESEARCH DESIGN: PRESTO sentence lists were presented to three groups of normal-hearing listeners in noise (multitalker babble [MTB] at 0 dB signal-to-noise ratio) or under eight-channel cochlear implant simulation (CI Sim). STUDY SAMPLE: Ninety-one young native speakers of English who were undergraduate students from the Indiana University community participated in this study. DATA COLLECTION AND ANALYSIS: Participants completed a sentence recognition task using different PRESTO sentence lists. They listened to sentences presented over headphones and typed in the words they heard on a computer. Keyword scoring was completed offline. Equivalency for sentence lists was determined based on the list intelligibility (mean keyword accuracy for each list compared with all other lists) and listener consistency (the relation between mean keyword accuracy on each list for each listener). RESULTS: Based on measures of list equivalency and listener consistency, ten PRESTO lists were found to be equivalent in the MTB condition, nine lists were equivalent in the CI Sim condition, and six PRESTO lists were equivalent in both conditions. CONCLUSIONS: PRESTO is a valuable addition to the clinical toolbox for assessing sentence recognition across different populations. Because the test condition influenced the overall intelligibility of lists, researchers and clinicians should take the presentation conditions into consideration when selecting the best PRESTO lists for their research or clinical protocols. PMID- 26134728 TI - Body mass index and functional status in community dwelling older Turkish males. AB - Disability is utmost important on an aging population's health. Obesity is associated with increased risk for disability. On-the-other-hand, higher-BMI is reported as associated with better functionality in older people in some reports defined as "obesity paradox". There is some evidence on differential relationship between body weight status and functionality by living setting gender, and different populations. We studied the relation between body mass index and functionality in Turkish community dwelling older males accounting for the most confounding factors: age, multimorbidity, polypharmacy and nutritional status. This is a cross-sectional study in a geriatric outpatient clinic of a university hospital. Functionality was assessed with evaluation of activities of daily living (ADL) and instrumental activities of daily living (IADL) scales. Nutrition was assessed by mini-nutritional assessment test. Two hundred seventy-four subjects comprised our study cohort. Mean age was 74.4 +/- 7.1 years, BMI was 25.8 +/- 4.4 kg/m(2). Linear regression analysis revealed significant and independent association of lower BMI with higher ADL and IADL scores (B = 0.047 and B = 0.128, respectively) (p < 0.05) and better nutritional status (B = 1.94 and B = 3.05, respectively) (p < 0.001) but not with the total number of medications. Higher IADL score was associated with younger age and lower total number of diseases (B = 0.121, B = 0.595, respectively) (p < 0.05) while ADL was not. We suggest that lower BMI is associated with better functional status in Turkish community-dwelling male older people. Our study recommends longitudinal studies with higher participants from different populations, genders and living settings are needed to comment more. PMID- 26134729 TI - External ear canal lesions of crusted scabies: A pitfall of recurrence? PMID- 26134730 TI - Re: Predictive value of cervical length in women with twin pregnancy presenting with threatened preterm labor. N. Melamed, L. Hiersch, R. Gabbay-Benziv, R. Bardin, I. Meizner, A. Wiznitzer and Y. Yogev. Ultrasound Obstet Gynecol 2015; 46: 73-81. PMID- 26134731 TI - Re: Maternal cardiac function, uteroplacental Doppler flow parameters and pregnancy outcome: a systematic review. M. A. M. Kampman, C. M. Bilardo, B. J. M. Mulder, J. G. Aarnoudse, C. Ris-Stalpers, D. J. van Veldhuisen and P. G. Pieper. Ultrasound Obstet Gynecol 2015; 46: 21-28. PMID- 26134732 TI - Reply: examining the reproducibility of ultrasound techniques. PMID- 26134733 TI - Reproducibility of Doppler evaluation: need to include physiological variation in determination of achievable ICCs. PMID- 26134734 TI - Erratum. PMID- 26134735 TI - Therapeutic Ultrasound as a Potential Male Dog Contraceptive: Determination of the Most Effective Application Protocol. AB - Ultrasound is one of the most promising forms of non-invasive contraception and has been studied in several animal models. The objective of the current investigation was to determine the most practical and effective application protocol for dog sterilization. A total of 100 dogs were divided into five equal groups. Group A received 5-min applications three times performed at 48-hr intervals and covering the entire testicular area at frequency of 1 MHz; Group B received 5-min applications three times performed at 48-hr intervals over the dorso-cranial area of the testis at frequency of 3 MHz; Group C received three sequential 5-min applications (at 5-min intervals between applications) covering the entire testicular area at frequency of 1 MHz; Group D received 15-min applications two times performed at 48-hr intervals and covering the entire testicular area at frequency of 1 MHz. The experimental groups' ultrasound had an intensity of 1.5W/cm(2) . The Control Group had the same procedure as Group A, but with the transducer switched-off. Dogs were surgically castrated 40 days following the treatment for histological examination. Azoospermia, testicular volume reduction and apparently irreversible testicular damage were achieved by Group A. No effects were noticed in the other groups. Testosterone levels remained within physiological range with all application protocols. A regimen of three applications of ultrasound at 1 MHz, and 1.5 W/cm(2) , lasting 5 min with an interval of 48 h was effective as permanent sterilization in the dog without hormonal impact. PMID- 26134736 TI - Probing the Dynamics of the Metallic-to-Semiconducting Structural Phase Transformation in MoS2 Crystals. AB - We have investigated the phase transformation of bulk MoS2 crystals from the metastable metallic 1T/1T' phase to the thermodynamically stable semiconducting 2H phase. The metastable 1T/1T' material was prepared by Li intercalation and deintercalation. The thermally driven kinetics of the phase transformation were studied with in situ Raman and optical reflection spectroscopies and yield an activation energy of 400 +/- 60 meV (38 +/- 6 kJ/mol). We calculate the expected minimum energy pathways for these transformations using DFT methods. The experimental activation energy corresponds approximately to the theoretical barrier for a single formula unit, suggesting that nucleation of the phase transformation is quite local. We also report that femtosecond laser writing converts 1T/1T' to 2H in a single laser pass. The mechanisms for the phase transformation are discussed. PMID- 26134737 TI - Computational Modeling of Multiphase Reactors. AB - Multiphase reactors are very common in chemical industry, and numerous review articles exist that are focused on types of reactors, such as bubble columns, trickle beds, fluid catalytic beds, etc. Currently, there is a high degree of empiricism in the design process of such reactors owing to the complexity of coupled flow and reaction mechanisms. Hence, we focus on synthesizing recent advances in computational and experimental techniques that will enable future designs of such reactors in a more rational manner by exploring a large design space with high-fidelity models (computational fluid dynamics and computational chemistry models) that are validated with high-fidelity measurements (tomography and other detailed spatial measurements) to provide a high degree of rigor. Understanding the spatial distributions of dispersed phases and their interaction during scale up are key challenges that were traditionally addressed through pilot scale experiments, but now can be addressed through advanced modeling. PMID- 26134739 TI - Design Criteria for Future Fuels and Related Power Systems Addressing the Impacts of Non-CO2 Pollutants on Human Health and Climate Change. AB - Concerns over the economics, supply chain, and emissions of greenhouse gases associated with the wide use of fossil fuels have led to increasing interest in developing alternative and renewable fuels for stationary power generation and transportation systems. Although there is considerable uncertainty regarding the economic and environmental impacts of alternative and renewable fuels, there is a great need for assessment of potential and emerging fuels to guide research priorities and infrastructure investment. Likewise, there is a great need to identify potential unintended adverse impacts of new fuels and related power systems before they are widely adopted. Historically, the environmental impacts of emerging fuels and power systems have largely focused on carbon dioxide emissions, often called the carbon footprint, which is used to assess impacts on climate change. Such assessments largely ignore the large impacts of emissions of other air pollutants. Given the potential changes in emissions of air pollutants associated with the large-scale use of new and emerging fuels and power systems, there is a great need to better guide efforts to develop new fuels and power systems that can avoid unexpected adverse impacts on the environment and human health. This review covers the nature of emissions, including the key components and impacts from the use of fuels, and the design criteria for future fuels and associated power systems to assure that the non-CO2 adverse impacts of stationary power generation and transportation are minimized. PMID- 26134740 TI - Accurate 3D temperature dosimetry during hyperthermia therapy by combining invasive measurements and patient-specific simulations. AB - PURPOSE: Dosimetry during deep local hyperthermia treatments in the head and neck currently relies on a limited number of invasively placed temperature sensors. The purpose of this study was to assess the feasibility of 3D dosimetry based on patient-specific temperature simulations and sensory feedback. MATERIALS AND METHODS: The study includes 10 patients with invasive thermometry applied in at least two treatments. Based on their invasive thermometry, we optimised patient group thermal conductivity and perfusion values for muscle, fat and tumour using a 'leave-one-out' approach. Next, we compared the accuracy of the predicted temperature (DeltaT) and the hyperthermia treatment quality (DeltaT50) of the optimisations based on the patient-group properties to those based on patient specific properties, which were optimised using previous treatment measurements. As a robustness check, and to enable comparisons with previous studies, we optimised the parameters not only for an applicator efficiency factor of 40%, but also for 100% efficiency. RESULTS: The accuracy of the predicted temperature (DeltaT) improved significantly using patient-specific tissue properties, i.e. 1.0 degrees C (inter-quartile range (IQR) 0.8 degrees C) compared to 1.3 degrees C (IQR 0.7 degrees C) for patient-group averaged tissue properties for 100% applicator efficiency. A similar accuracy was found for optimisations using an applicator efficiency factor of 40%, indicating the robustness of the optimisation method. Moreover, in eight patients with repeated measurements in the target region, DeltaT50 significantly improved, i.e. DeltaT50 reduced from 0.9 degrees C (IQR 0.8 degrees C) to 0.4 degrees C (IQR 0.5 degrees C) using an applicator efficiency factor of 40%. CONCLUSION: This study shows that patient specific temperature simulations combined with tissue property reconstruction from sensory data provides accurate minimally invasive 3D dosimetry during hyperthermia treatments: T50 in sessions without invasive measurements can be predicted with a median accuracy of 0.4 degrees C. PMID- 26134738 TI - Microfluidic Strategies for Understanding the Mechanics of Cells and Cell-Mimetic Systems. AB - Microfluidic systems are attracting increasing interest for the high-throughput measurement of cellular biophysical properties and for the creation of engineered cellular microenvironments. Here we review recent applications of microfluidic technologies to the mechanics of living cells and synthetic cell-mimetic systems. We begin by discussing the use of microfluidic devices to dissect the mechanics of cellular mimics, such as capsules and vesicles. We then explore applications to circulating cells, including erythrocytes and other normal blood cells, and rare populations with potential disease diagnostic value, such as circulating tumor cells. We conclude by discussing how microfluidic devices have been used to investigate the mechanics, chemotaxis, and invasive migration of adherent cells. In these ways, microfluidic technologies represent an increasingly important toolbox for investigating cellular mechanics and motility at high throughput and in a format that lends itself to clinical translation. PMID- 26134741 TI - Temperature dependence of acoustic harmonics generated by nonlinear ultrasound beam propagation in ex vivo tissue and tissue-mimicking phantoms. AB - PURPOSE: Hyperthermia is a cancer treatment technique that could be delivered as a stand-alone modality or in conjunction with chemotherapy or radiation therapy. Noninvasive and real-time temperature monitoring of the heated tissue improves the efficacy and safety of the treatment. A temperature-sensitive acoustic parameter is required for ultrasound-based thermometry. In this paper the amplitude and the energy of the acoustic harmonics of the ultrasound backscattered signal are proposed as suitable parameters for noninvasive ultrasound thermometry. MATERIALS AND METHODS: A commercial high frequency ultrasound imaging system was used to generate and detect acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues. The pressure amplitude and the energy content of the backscattered fundamental frequency (p1 and E1), the second (p2 and E2) and the third (p3 and E3) harmonics were detected in pulse-echo mode. Temperature was increased from 26 degrees to 46 degrees C uniformly through both samples. The amplitude and the energy content of the harmonics and their ratio were measured and analysed as a function of temperature. RESULTS: The average p1, p2 and p3 increased by 69%, 100% and 283%, respectively as the temperature was elevated from 26 degrees to 46 degrees C in tissue samples. In the same experiment the average E1, E2 and E3 increased by 163%, 281% and 2257%, respectively. A similar trend was observed in tissue mimicking gel phantoms. CONCLUSIONS: The findings suggest that the harmonics generated due to nonlinear ultrasound beam propagation are highly sensitive to temperature and could potentially be used for noninvasive ultrasound tissue thermometry. PMID- 26134742 TI - Facile room-temperature solution-phase synthesis of a spherical covalent organic framework for high-resolution chromatographic separation. AB - A simple and facile room-temperature solution-phase synthesis was developed to fabricate a spherical covalent organic framework with large surface area, good solvent stability and high thermostability for high-resolution chromatographic separation of diverse important industrial analytes including alkanes, cyclohexane and benzene, alpha-pinene and beta-pinene, and alcohols with high column efficiency and good precision. PMID- 26134743 TI - Conjugated Polythiophene for Rapid, Simple, and High-Throughput Screening of Antimicrobial Photosensitizers. AB - The cationic conjugated poly[3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5 thiophene hydrochloride] (PMNT) has been developed for high-throughput screening of photodynamic antimicrobial chemotherapy photosensitizers (PSs). The bacterial number can be detected quantitatively by PMNT via various fluorescence quenching efficiencies. The photosensitized inactivation of bacteria is not efficient with ineffective PSs, and thus the bacteria grow exponentially and can be coated tightly by PMNT through electrostatic and hydrophobic interactions, resulting in aggregates and fluorescence quenching of PMNT, whereas, conversely, effective PSs lead to original and strong fluorescence of PMNT. This new platform of high throughput screening is promising for discovering new PSs. PMID- 26134744 TI - Kinetic and Thermodynamic Fragilities of Square Well Fluids with Tunable Barriers to Bond Breaking. AB - An understanding of the origin of fragility, which the rapidity of change of viscosity and related dynamical quantities, has been sought by a variety of approaches over the years. Within the framework of the Adam-Gibbs relation, fragility is in principle related to both the temperature variation of configurational entropy and the high temperature activation energy. Many theoretical analyses have been focused on the variation of configuration entropy, although the importance of the high temperature activation energy in determining the fragility of a glass former has also been emphasized. We explore the latter aspect by considering a model liquid whose high temperature activation energy is modified by hand, through the introduction of a tunable barrier to bond breaking. We show that changes in such a barrier are able to modify the fragility measured from the temperature dependence of dynamical quantities, while a thermodynamic measure of fragility obtained from the configurational entropy remains unchanged. We discuss the implications of our results to our understanding of fragility, and outline open questions that merit further investigation. PMID- 26134745 TI - Ag-mediated cascade decarboxylative coupling and annulation: a convenient route to 2-phosphinobenzo[b]phosphole oxides. AB - The first facile and practical silver-mediated cascade reaction of arylpropiolic acids with diarylphosphine oxides has been developed, providing a general, one step approach to structurally sophisticated 2-phosphinobenzo[b]phosphole oxide frameworks of importance in materials science via sequential decarboxylative C-P cross-coupling and C-H/P-H functionalization with operational simplicity and excellent functional group compatibility. PMID- 26134746 TI - Synthesis of Multishell Nanoplates by Consecutive Epitaxial Growth of Bi2Se3 and Bi2Te3 Nanoplates and Enhanced Thermoelectric Properties. AB - We herein demonstrate the successive epitaxial growth of Bi2Te3 and Bi2Se3 on seed nanoplates for the scalable synthesis of heterostructured nanoplates (Bi2Se3@Bi2Te3) and multishell nanoplates (Bi2Se3@Bi2Te3@Bi2Se3, Bi2Se3@Bi2Te3@Bi2Se3@Bi2Te3). The relative dimensions of the constituting layers are controllable via the molar ratios of the precursors added to the seed nanoplate solution. Reduction of the precursors produces nanoparticles that attach preferentially to the sides of the seed nanoplates. Once attached, the nanoparticles reorganize epitaxially on the seed crystal lattices to form single crystalline core-shell nanoplates. The nanoplates, initially 100 nm wide, grew laterally to 620 nm in the multishell structure, while their thickness increased more moderately, from 5 to 20 nm. The nanoplates were pelletized into bulk samples by spark plasma sintering and their thermoelectric properties are compared. A peak thermoelectric figure of merit (ZT) ~0.71 was obtained at 450 K for the bulk of Bi2Se3@Bi2Te3 nanoplates by simultaneous modulation of electronic and thermal transport in the presence of highly dense grain and phase boundaries. PMID- 26134747 TI - Multiple sclerosis and Parkinson's disease: the two faces of neurodegeneration. Report of the first Greek case and review of the literature. AB - There is still an open debate whether multiple sclerosis (MS) lesions can cause parkinsonian symptoms, or the coexistence of both diseases in the same patient is accidental. Moreover, alpha-synuclein (alpha Syn), the hallmark of Parkinson's disease (PD) seems also to play a crucial role in MS. So far, 42 cases of co occurrence of parkinsonism and MS have been reported, but CSF alpha Syn measurement is lacking. To our knowledge, we report the first case with concomitant MS and PD diagnosis based on both clinico-radiological and CSF alpha Syn findings and review of literature. PMID- 26134748 TI - Wide-Bandgap Benzodithiophene-Benzothiadiazole Copolymers for Highly Efficient Multijunction Polymer Solar Cells. AB - Novel wide-bandgap semiconducting polymers are designed and synthesized for multijunction polymer solar cell (PSC) applications. In single-junction PSCs, BDT FBT-2T exhibits efficiencies exceeding 6.5% for active layer thicknesses between 90 and 250 nm, with the highest efficiency of 7.7% at 100 and 250 nm. This enables tandem PSCs to be created with an efficiency of 8.9%. PMID- 26134749 TI - IL-1beta: a key modulator in asthmatic airway smooth muscle hyper-reactivity. AB - Asthma is a chronic inflammatory disorder of the airway. It is characterized by airway hyper-reactivity, which can be attributed to the chronically inflamed airway. However, the molecular mechanism is still under investigation. In this article, we have shown that IL-1beta is a key molecule that can orchestrate both Toll-like receptor and muscarinic receptor pathways, and that antagonizing the function of IL-1beta has a promising future as a potential drug target for asthma treatment. IL-1beta can activate NF-kappaB pathways via Toll-like receptors, and NF-kappaB will eventually transactivate the genes of cytokines, chemokines, proteins of the complement system, adhesion molecules and immune receptors involved in inflammation. IL-1beta can activate eosinophils, which can release major basic protein (MBP) to antagonize the M2 receptors leading to excessive acetylcholine release. Acetylcholine has an effect on M3 receptors, which are related to airway smooth muscle contraction and mucus production. IL-1beta is reported to activate COX-2 resulting in heterologous desensitization of adenylate cyclase and impairs relaxation of the ASM. IL-1beta is involved in mediation of neutrophilic inflammation. Identification of the prominent role of IL-1beta in asthma could lead to successful use of anti-IL1beta agents. PMID- 26134750 TI - Safety and efficacy of paracetamol and NSAIDs in osteoarthritis: which drug to recommend? AB - INTRODUCTION: Osteoarthritis (OA) is the most common form of arthritis and is a major cause of disability, especially in people >= 45 years old. Several international societies recommend the use of both acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) to alleviate OA pain. However, patients with OA often have comorbidities, notably cardiovascular risk factors, which may hamper the use of these analgesics. AREAS COVERED: This paper reviews the safety of both acetaminophen and NSAIDs in OA. Recent data have pointed to a gastrointestinal and cardiovascular toxicity of acetaminophen, which has been neglected for a long time. In addition, several meta-analyses revealed that acetaminophen is a poor analgesic in OA. Traditional NSAIDs and cyclooxygenase 2 inhibitors (coxibs) have similar analgesic effects but vary greatly in their potential gastrointestinal and cardiovascular toxicity. EXPERT OPINION: Given the putative gastrointestinal and cardiovascular toxicity and poor analgesic properties of acetaminophen in OA, its use in patients with risk factors is questionable. Acetaminophen should be used at the lowest effective dosage and for the shortest time in all OA patients. Given the different safety profiles, the choice of NSAIDs, traditional or coxibs, should be based on individual patient risk factors. A good knowledge of the different strategies to decrease the gastrointestinal and cardiovascular toxic effects of NSAIDs is key to the management of OA. PMID- 26134752 TI - Retraction: Concurrent Suppression of Integrin alpha5, radixin, and RhoA phenocopies the effects of miR-31 on metastasis. PMID- 26134753 TI - Down-regulation of STAT3 expression using vector-based RNA interference promotes apoptosis in Hepatocarcinoma cells. AB - In this study, we followed a DNA vector-based RNAi approach to silence the signal transducer and activator of transcription 3 (STAT3) expression in Bel-7402 cells, to explore how the Janus kinase (JAK)/STAT3 signaling pathway influences the apoptosis of hepatocarcinoma cells. According to GenBank's STAT3 cDNA, the plasmid pGCsi.U6/neoRFP STAT3, which was designed for expression of STAT3 small interfering RNA (siRNA), was constructed and synthesized, and then transfected into Bel-7402 cells using Lipofectamine 2000. Cells with or without siRNA transfection were treated in wells. The apoptotic rate was detected by flow cytometry (FCM) and by staining with the Annexin V/propidium iodide (PI) apoptosis detection kit. Simultaneously, the mitochondrial membrane potential (DeltaPsim) was visualized by JC-1 fluorescence staining and observed using the inverted fluorescence microscope. Furthermore, the expression of caspase-3 protein was analyzed by Western blotting. The results showed that treatment with STAT3 siRNA displayed effects in the Bel-7402 cells, causing a significantly increased apoptotic ratio (P < 0.05). The mitochondrial membrane potential of the STAT3 siRNA group, observed by the JC-1 fluorescence staining, decreased significantly. The protein expression of active caspase-3 increased with STAT3 siRNA treatment, and was significantly higher than that of the control group (P < 0.05). STAT3 gene-silencing significantly improves the apoptotic effect against Bel-7402 cells. PMID- 26134754 TI - Single-bundle nanofiber based OFETs fabricated from a cyclic conjugated organogelator with high field-effect mobility and high photoresponsivity. AB - Single-bundle nanofiber based OFETs were fabricated from a cyclic conjugated organogelator, using a simple gelation method. The devices exhibited typical p type semiconductor properties with dominant hole transport both in the dark and upon illumination under ambient conditions. PMID- 26134755 TI - Occupational sensitization to lactase in the dietary supplement industry. AB - Aerogen lactase exposure carries a risk for the development of allergic asthma and rhinitis; only a few occupationally affected patients have been reported. The authors report the results of allergy testing with employees of a lactase tablets manufacturing plant. The survey involved 13 workers, including a questionnaire, spirometry, basophil activation test (BAT), and skin prick tests (SPTs) with lactase and a panel of common aeroallergens. Furthermore, lactase-specific immunoglobulin E (IgE) antibodies were analyzed. Sensitization to lactase could be proven for 9 workers by SPT and BAT; specific IgE antibodies could be detected in serum samples of all sensitized. However, IgE levels >=0.35 kU/L were only found in 4 sera. These data confirm that occupational exposure to lactase can induce IgE-mediated respiratory sensitization resulting in allergic diseases. Protective measures should thus be obligatory when working with lactase. PMID- 26134756 TI - Protective effect of ursodeoxycholic acid, resveratrol, and N-acetylcysteine on nonalcoholic fatty liver disease in rats. AB - CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Resveratrol (RSV) and N-acetylcysteine (NAC) are safe representatives of natural and synthetic antioxidants, respectively. OBJECTIVE: The objective of this study was to evaluate protective effects of RSV and NAC, compared with ursodeoxycholic acid (UDCA), on experimental NAFLD. MATERIALS AND METHODS: NAFLD was induced by feeding rats a methionine choline-deficient diet (MCDD) for four cycles, each of 4 d of MCDD feeding and 3 d of fasting. Animals were divided into normal control, steatosis control, and five treatment groups, receiving UDCA (25 mg/kg/d), RSV (10 mg/kg/d), NAC (20 mg/kg/d), UDCA + RSV, and UDCA + NAC orally for 28 d. Liver integrity markers (liver index and serum transaminases), serum tumor necrosis factor-alpha (TNF-alpha), glucose, albumin, renal functions (urea, creatinine), lipid profile (total cholesterol; TC, triglycerides, high density lipoproteins, low density lipoproteins; LDL-C, very low density lipoproteins, leptin), and oxidative stress markers (hepatic malondialdehyde; MDA, glutathione; GSH, glutathione-S-transferase; GST) were measured using automatic analyzer, colorimetric kits, and ELISA kits, supported by a liver histopathological study. RESULTS: RSV and NAC administration significantly improved liver index (RSV only), alanine transaminase (52, 52%), TNF-alpha (70, 70%), glucose (69, 80%), albumin (122, 114%), MDA (55, 63%), GSH (160, 152%), GST (84, 84%), TC (86, 86%), LDL-C (83, 81%), and leptin (59, 70%) levels compared with steatosis control values. A combination of RSV or NAC with UDCA seems to ameliorate their effects. DISCUSSION AND CONCLUSION: RSV and NAC are effective on NAFLD through antioxidant, anti-inflammatory, and lipid-lowering potentials, where as RSV seems better than UDCA or NAC. PMID- 26134757 TI - Identification of sesquiterpene coumarins of oleo-gum resin of Ferula assa foetida L. from the Yasuj region. AB - Chemical investigation of the oleo-gum resin of Ferula assa-foetida L. from Yasuj region led to the identification of five sesquiterpene coumarins namely, conferone (1), badrakemin (2), feslol (3), isosamarcandin (4) and samarcandin (5). The compounds were characterised by detailed 1D ((1)H and (13)C) and 2D NMR (HMBC, HSQC and NOESY) experiments. Among these compounds, conferone (1) and isosamarcandin (4) are being newly reported in F. assa-foetida L. PMID- 26134758 TI - Changes in genetic and environmental influences on disordered eating between early and late adolescence: a longitudinal twin study. AB - BACKGROUND: We investigated the genetic and environmental contributions to disordered eating (DE) between early and late adolescence in order to determine whether different sources of heritability and environmental risk contributed to these peak times of emergence of eating disorders. METHOD: Adolescent female twins from the Australian Twin Registry were interviewed over the telephone with the Eating Disorder Examination (EDE). Data were collected at 12-15 and 16-19 years (wave 1: N = 699, 351 pairs; wave 3: N = 499, 247 pairs). Assessments also involved self-report measures related to negative life events and weight-related peer teasing. RESULTS: Unstandardized estimates from the bivariate Cholesky decomposition model showed both genetic influences and non-shared environmental influences increased over adolescence, but shared environmental influences decreased. While non-shared environmental sources active at ages 12-15 years continued to contribute at 16-19 years, new sources of both additive genetic and non-shared environmental risk were introduced at ages 16-19 years. Weight-related peer teasing in early-mid adolescence predicted increases of DE in later adolescence, while negative life events did not. CONCLUSIONS: Two-thirds of the heritable influence contributing to DE in late adolescence was unique to this age group. During late adolescence independent sources of genetic risk, as well as environmental influences are likely to be related in part to peer teasing, appear key antecedents in growth of DE. PMID- 26134759 TI - Binding of MMP-9-degraded fibronectin to beta6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer. AB - Fibronectin (FN) has been recognized as the key element in promoting cell adhesion, migration and oncogenic transformation. alphavbeta6 integrin binds with FN in an RGD-dependent manner and is associated with invasion and poor prognosis in many types of cancers. The extracellular matrix (ECM) is commonly degraded and becomes disorganized in cancers. Previous studies have shown that FN can be degraded into fragments by MMP-9 in vitro; MMP-9 expression is upregulated in breast cancer, therefore, the role of degraded FN in breast cancer progression needs to be investigated. In the present study, expression of beta6 integrin in breast cancer tissues was analyzed. The data were quite consistent with the hypothesis that beta6 integrin expression is an indicator of poor prognosis. Cell surface expression of beta6 integrin was correlated with the invasive behavior of the breast cancer cell lines. MMP-9-degraded FN was used to explore its effects on cell invasion and expression of beta6 integrin. The results indicated that MMP 9-degraded FN can adjust constituents of the alphavbeta6 heterodimers at the early phase and significantly elevate amounts of beta6 integrin subunits at a later period. To better elucidate the mechanism by which beta6 integrin regulates FN-induced cell migration and invasion, we determined the expression and activity of the downstream kinases of beta6 integrin, and elucidated that focal adhesion kinase (FAK)-Src interaction promoted the invasion and migration of breast cancer cells after treatment of MMP-9-degraded FN through the Erk1/2 and PI3K/Akt/Smad 1/5/8 pathways. PMID- 26134760 TI - Pulp canal obliteration after replantation of avulsed immature teeth: a systematic review. AB - BACKGROUND: Avulsion of permanent teeth is one of the most serious dento-alveolar traumatic injuries. Pulp canal obliteration (PCO) is one of the consequences after replantation of avulsed immature teeth. The aim of this systematic review was to determine when calcification following replantation of an avulsed immature tooth begins and to evaluate the prevalence of PCO in these cases. MATERIALS AND METHODS: Electronic database MEDLINE via Ovid, PubMed, Cochrane, and Web of science databases were searched. Hand searching was performed through reference lists of endodontic and trauma textbooks, endodontic and trauma-related journals, and relevant articles from electronic searching. Pooled data from the selected articles were analyzed for prevalence of healing and PCO as well as mean first evidence of PCO. RESULTS: Pulp healing after replantation of immature teeth occurred in 32.9%, while pulpal necrosis occurred in 67.1% of teeth. PCO was the most frequent outcome of pulpal healing as it occurred in 96% of healed pulps. First evidence of obliteration was observed from 3 to 14 months with mean time of 9.5 months (95% CI = 4.5-14.5 months). CONCLUSIONS: PCO is considered the mechanism by which the pulp heals after replantation of avulsed immature permanent teeth. PCO is very fast and can be recognized radiographically during the first year from the onset of the trauma. PMID- 26134761 TI - Serum cardiac troponin I concentrations decrease following treatment of primary immune-mediated haemolytic anaemia. AB - OBJECTIVES: The measurement of serum cardiac troponin I concentrations in dogs with a range of non-primary cardiac illnesses suggests that cardiac myocyte damage is commonplace. Dogs with primary immune-mediated haemolytic anaemia have increased serum cardiac troponin I concentrations at the time of diagnosis. However, it is unclear whether biochemical evidence of cardiac myocyte damage improves following successful treatment of anaemia. METHODS: A haematology profile was performed and serum cardiac troponin I concentrations were measured in 19 dogs with primary immune-mediated haemolytic anaemia before and after treatment. RESULTS: The haematocrit increased significantly (P = 0 . 0001) following treatment of primary IMHA (median pre: 0 . 13 L/L, median post: 0 . 33 L/L). The serum cardiac troponin I concentrations decreased significantly (P < 0 . 05) after treatment (median pre: 0 . 26 ng/mL, median post: 0 . 16 ng/mL). CLINICAL SIGNIFICANCE: Serum cardiac troponin I concentration decreases following successful treatment of primary immune-mediated haemolytic anaemia. The clinical and prognostic significance of serum cardiac troponin I concentrations before and after treatment in dogs with primary immune-mediated haemolytic anaemia merits further investigation. PMID- 26134762 TI - Survival after Gastrectomy in Node-Negative Gastric Cancer: A Review and Meta Analysis of Prognostic Factors. AB - BACKGROUND: Lymph node metastasis is one of the most important prognostic factors for survival of patients with gastric cancer (GC) after surgical resection. Nevertheless, a considerable number of patients have node-negative disease. We performed the present systematic review to evaluate survival and identify prognostic factors in node-negative GC patients undergoing curative intent resection. MATERIAL AND METHODS: Relevant studies published between January 2000 and January 2015 were identified by searching the PubMed database and reviewed systematically. Summary relative risks (RR) and 95% confidence intervals (95% CI) were estimated using random-effects models. RESULTS: Thirty observational studies involving 12 504 patients were included in the review. Median 5-year overall survival was 84.3% (range, 53-96.3%). Pooled analysis showed that old age (RR, 1.26; 95%CI, 1.13-1.42), 3 were more sensitive to A-1155463. Consistently, cell lines with high expression of BCL-XL and NOXA, a pro-apoptotic protein that antagonizes MCL-1 activity were sensitive to A-1155463. Silencing the expression of BCL-X(L) via siRNA killed the cell lines that were sensitive to A-1155463 while having little effect on lines that were resistant. Furthermore, silencing the expression of MCL-1 in resistant cell lines conferred sensitivity to A-1155463, whereas silencing NOXA abrogated sensitivity. CONCLUSIONS: This work demonstrates the utility of characterizing frequent genomic alterations to identify cancer survival genes. In addition, these studies demonstrate the utility of the highly potent and selective compound A-1155463 for investigating the role of BCL-X(L) in mediating the survival of specific tumor types, and indicate that BCL-X(L) inhibition could be an effective treatment for colorectal tumors with high BCL X(L) and NOXA expression. PMID- 26134787 TI - Acyl-CoA N-acyltransferase influences fertility by regulating lipid metabolism and jasmonic acid biogenesis in cotton. AB - Cotton (Gossypium spp.) is an important economic crop and there is obvious heterosis in cotton, fertility has played an important role in this heterosis. However, the genes that exhibit critical roles in anther development and fertility are not well understood. Here, we report an acyl-CoA N-acyltransferase (EC2.3; GhACNAT) that plays a key role in anther development and fertility. Suppression of GhACNAT by virus-induced gene silencing in transgenic cotton (G. hirsutum L. cv. C312) resulted in indehiscent anthers that were full of pollen, diminished filaments and stamens, and plant sterility. We found GhACNAT was involved in lipid metabolism and jasmonic acid (JA) biosynthesis. The genes differentially expressed in GhACNAT-silenced plants and C312 were mainly involved in catalytic activity and transcription regulator activity in lipid metabolism. In GhACNAT-silenced plants, the expression levels of genes involved in lipid metabolism and jasmonic acid biosynthesis were significantly changed, the amount of JA in leaves and reproductive organs was significantly decreased compared with the amounts in C312. Treatments with exogenous methyl jasmonate rescued anther dehiscence and pollen release in GhACNAT-silenced plants and caused self fertility. The GhACNAT gene may play an important role in controlling cotton fertility by regulating the pathways of lipid synthesis and JA biogenesis. PMID- 26134789 TI - Compound focusing mirror and X-ray waveguide optics for coherent imaging and nano diffraction. AB - A compound optical system for coherent focusing and imaging at the nanoscale is reported, realised by high-gain fixed-curvature elliptical mirrors in combination with X-ray waveguide optics or different cleaning apertures. The key optical concepts are illustrated, as implemented at the Gottingen Instrument for Nano Imaging with X-rays (GINIX), installed at the P10 coherence beamline of the PETRA III storage ring at DESY, Hamburg, and examples for typical applications in biological imaging are given. Characteristic beam configurations with the recently achieved values are also described, meeting the different requirements of the applications, such as spot size, coherence or bandwidth. The emphasis of this work is on the different beam shaping, filtering and characterization methods. PMID- 26134788 TI - Identification of Alp1U and Lom6 as epoxy hydrolases and implications for kinamycin and lomaiviticin biosynthesis. AB - The naturally occurring diazobenzofluorenes, kinamycins, fluostatins and lomaiviticins, possess highly oxygenated A-rings, via which the last forms a dimeric pharmacophore. However, neither the A-ring transformation nor the dimerization mechanisms have been explored thus far. Here we propose a unified biosynthetic logic for the three types of antibiotics and verify one key reaction via detailed genetic and enzymatic experiments. Alp1U and Lom6 from the kinamycin and lomaiviticin biosynthesis, respectively, are shown to catalyse epoxy hydrolysis on a substrate that is obtained by chemical deacetylation of a kinamycin-pathway-derived intermediate. Thus, our study provides the first evidence for the existence of an epoxy intermediate in lomaiviticin biosynthesis. Furthermore, our results suggest that the dimerization in the lomaiviticin biosynthesis proceeds after dehydration of a product generated by Lom6. PMID- 26134790 TI - Vibration measurements of high-heat-load monochromators for DESY PETRA III extension. AB - The requirement for vibrational stability of beamline optics continues to evolve rapidly to comply with the demands created by the improved brilliance of the third-generation low-emittance storage rings around the world. The challenge is to quantify the performance of the instrument before it is installed at the beamline. In this article, measurement techniques are presented that directly and accurately measure (i) the relative vibration between the two crystals of a double-crystal monochromator (DCM) and (ii) the absolute vibration of the second crystal cage of a DCM. Excluding a synchrotron beam, the measurements are conducted under in situ conditions, connected to a liquid-nitrogen cryocooler. The investigated DCM utilizes a direct-drive (no gearing) goniometer for the Bragg rotation. The main causes of the DCM vibration are found to be the servoing of the direct-drive goniometer and the flexibility in the crystal cage motion stages. It is found that the investigated DCM can offer relative pitch vibration down to 48 nrad RMS (capacitive sensors, 0-5 kHz bandwidth) and absolute pitch vibration down to 82 nrad RMS (laser interferometer, 0-50 kHz bandwidth), with the Bragg axis brake engaged. PMID- 26134791 TI - X-ray pulse wavefront metrology using speckle tracking. AB - An instrument allowing the quantitative analysis of X-ray pulsed wavefronts is presented and its processing method explained. The system relies on the X-ray speckle tracking principle to accurately measure the phase gradient of the X-ray beam from which beam optical aberrations can be deduced. The key component of this instrument, a semi-transparent scintillator emitting visible light while transmitting X-rays, allows simultaneous recording of two speckle images at two different propagation distances from the X-ray source. The speckle tracking procedure for a reference-less metrology mode is described with a detailed account on the advanced processing schemes used. A method to characterize and compensate for the imaging detector distortion, whose principle is also based on speckle, is included. The presented instrument is expected to find interest at synchrotrons and at the new X-ray free-electron laser sources under development worldwide where successful exploitation of beams relies on the availability of an accurate wavefront metrology. PMID- 26134792 TI - PRIGo: a new multi-axis goniometer for macromolecular crystallography. AB - The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high precision goniometer providing an alternative to (mini-)kappa, traditional three circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around omega and consists of four linear positioners working synchronously to achieve x, y, z translations and chi rotation (0-90 degrees ), followed by a phi stage (0-360 degrees ) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 um, <7 um and <10 um for omega, chi and phi, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described. PMID- 26134793 TI - Design and performance of the APPLE-Knot undulator. AB - Along with the development of accelerator technology, synchrotron emittance has continuously decreased. This results in increased brightness, but also causes a heavy heat load on beamline optics. Recently, optical surfaces with 0.1 nm micro roughness and 0.05 urad slope error (r.m.s.) have become commercially available and surface distortions due to heat load have become a key factor in determining beamline performance, and heat load has become a serious problem at modern synchrotron radiation facilities. Here, APPLE-Knot undulators which can generate photons with arbitrary polarization, with low on-axis heat load, are reported. PMID- 26134794 TI - The Extreme Conditions Beamline P02.2 and the Extreme Conditions Science Infrastructure at PETRA III. AB - A detailed description is presented of the Extreme Conditions Beamline P02.2 for micro X-ray diffraction studies of matter at simultaneous high pressure and high/low temperatures at PETRA III, in Hamburg, Germany. This includes performance of the X-ray optics and instrumental resolution as well as an overview of the different sample environments available for high-pressure studies in the diamond anvil cell. Particularly emphasized are the high-brilliance and high-energy X-ray diffraction capabilities of the beamline in conjunction with the use of fast area detectors to conduct time-resolved compression studies in the millisecond time regime. Finally, the current capability of the Extreme Conditions Science Infrastructure to support high-pressure research at the Extreme Conditions Beamline and other PETRA III beamlines is described. PMID- 26134795 TI - Two-dimensional in situ metrology of X-ray mirrors using the speckle scanning technique. AB - In situ metrology overcomes many of the limitations of existing metrology techniques and is capable of exceeding the performance of present-day optics. A novel technique for precisely characterizing an X-ray bimorph mirror and deducing its two-dimensional (2D) slope error map is presented. This technique has also been used to perform fast optimization of a bimorph mirror using the derived 2D piezo response functions. The measured focused beam size was significantly reduced after the optimization, and the slope error map was then verified by using geometrical optics to simulate the focused beam profile. This proposed technique is expected to be valuable for in situ metrology of X-ray mirrors at synchrotron radiation facilities and in astronomical telescopes. PMID- 26134796 TI - A simple optical system delivering a tunable micrometer pink beam that can compensate for heat-induced deformations. AB - The radiation from an undulator reflected from one or more optical elements (usually termed 'pink-beam') is used in photon-hungry experiments. The optical elements serve as a high-energy cutoff and for focusing purposes. One of the issues with this configuration is maintaining the focal spot dimension as the energy of the undulator is varied, since this changes the heat load absorbed by the first optical element. Finite-element analyses of the power absorbed by a side water-cooled mirror exposed to the radiation emitted by an undulator at the Advanced Photon Source (APS) and at the APS after the proposed upgrade (APSU) reveals that the mirror deformation is very close to a convex cylinder creating a virtual source closer to the mirror than the undulator source. Here a simple optical system is described based on a Kirkpatrick-Baez pair which keeps the focus size to less than 2 um (in the APSU case) with a working distance of 350 mm despite the heat-load-induced change in source distance. Detailed ray tracings at several photon energies for both the APS and APSU show that slightly decreasing the angle of incidence on the mirrors corrects the change in the 'virtual' position of the source. The system delivers more than 70% of the first undulator harmonic with very low higher-orders contamination for energies between 5 and 10 keV. PMID- 26134797 TI - Focusing performance of a multilayer Laue lens with layer placement error described by dynamical diffraction theory. AB - The multilayer Laue lens (MLL) is essentially a linear zone plate with large aspect ratio, which can theoretically focus hard X-rays to well below 1 nm with high efficiency when ideal structures are used. However, the focusing performance of a MLL depends heavily on the quality of the layers, especially the layer placement error which always exists in real MLLs. Here, a dynamical modeling approach, based on the coupled wave theory, is proposed to study the focusing performance of a MLL with layer placement error. The result of simulation shows that this method can be applied to various forms of layer placement error. PMID- 26134798 TI - A phase-space beam position monitor for synchrotron radiation. AB - The stability of the photon beam position on synchrotron beamlines is critical for most if not all synchrotron radiation experiments. The position of the beam at the experiment or optical element location is set by the position and angle of the electron beam source as it traverses the magnetic field of the bend-magnet or insertion device. Thus an ideal photon beam monitor would be able to simultaneously measure the photon beam's position and angle, and thus infer the electron beam's position in phase space. X-ray diffraction is commonly used to prepare monochromatic beams on X-ray beamlines usually in the form of a double crystal monochromator. Diffraction couples the photon wavelength or energy to the incident angle on the lattice planes within the crystal. The beam from such a monochromator will contain a spread of energies due to the vertical divergence of the photon beam from the source. This range of energies can easily cover the absorption edge of a filter element such as iodine at 33.17 keV. A vertical profile measurement of the photon beam footprint with and without the filter can be used to determine the vertical centroid position and angle of the photon beam. In the measurements described here an imaging detector is used to measure these vertical profiles with an iodine filter that horizontally covers part of the monochromatic beam. The goal was to investigate the use of a combined monochromator, filter and detector as a phase-space beam position monitor. The system was tested for sensitivity to position and angle under a number of synchrotron operating conditions, such as normal operations and special operating modes where the photon beam is intentionally altered in position and angle at the source point. The results are comparable with other methods of beam position measurement and indicate that such a system is feasible in situations where part of the synchrotron beam can be used for the phase-space measurement. PMID- 26134799 TI - Development of variable-magnification X-ray Bragg optics. AB - A novel X-ray Bragg optics is proposed for variable-magnification of an X-ray beam. This X-ray Bragg optics is composed of two magnifiers in a crossed arrangement, and the magnification factor, M, is controlled through the azimuth angle of each magnifier. The basic properties of the X-ray optics such as the magnification factor, image transformation matrix and intrinsic acceptance angle are described based on the dynamical theory of X-ray diffraction. The feasibility of the variable-magnification X-ray Bragg optics was verified at the vertical wiggler beamline BL-14B of the Photon Factory. For X-ray Bragg magnifiers, Si(220) crystals with an asymmetric angle of 14 degrees were used. The magnification factor was calculated to be tunable between 0.1 and 10.0 at a wavelength of 0.112 nm. At various magnification factors (M >= 1.0), X-ray images of a nylon mesh were observed with an air-cooled X-ray CCD camera. Image deformation caused by the optics could be corrected by using a 2 * 2 transformation matrix and bilinear interpolation method. Not only absorption contrast but also edge-contrast due to Fresnel diffraction was observed in the magnified images. PMID- 26134800 TI - Resonant inelastic X-ray scattering spectrometer with 25 meV resolution at the Cu K-edge. AB - An unparalleled resolution is reported with an inelastic X-ray scattering instrument at the Cu K-edge. Based on a segmented concave analyzer, featuring single-crystal quartz (SiO2) pixels, the spectrometer delivers a resolution near 25 meV (FWHM) at 8981 eV. Besides the quartz analyzer, the performance of the spectrometer relies on a four-bounce Si(553) high-resolution monochromator and focusing Kirkpatrick-Baez optics. The measured resolution agrees with the ray tracing simulation of an ideal spectrometer. The performance of the spectrometer is demonstrated by reproducing the phonon dispersion curve of a beryllium single crystal. PMID- 26134801 TI - HERMES: a soft X-ray beamline dedicated to X-ray microscopy. AB - The HERMES beamline (High Efficiency and Resolution beamline dedicated to X-ray Microscopy and Electron Spectroscopy), built at Synchrotron SOLEIL (Saint-Auban, France), is dedicated to soft X-ray microscopy. The beamline combines two complementary microscopy methods: XPEEM (X-ray Photo Emitted Electron Microscopy) and STXM (Scanning Transmission X-ray Microscopy) with an aim to reach spatial resolution below 20 nm and to fully exploit the local spectroscopic capabilities of the two microscopes. The availability of the two methods within the same beamline enables the users to select the appropriate approach to study their specific case in terms of sample environment, spectroscopy methods, probing depth etc. In this paper a general description of the beamline and its design are presented. The performance and specifications of the beamline will be reviewed in detail. Moreover, the article is aiming to demonstrate how the beamline performances have been specifically optimized to fulfill the specific requirements of a soft X-ray microscopy beamline in terms of flux, resolution, beam size etc. Special attention has been dedicated to overcome some limiting and hindering problems that are usually encountered on soft X-ray beamlines such as carbon contamination, thermal stability and spectral purity. PMID- 26134802 TI - Laue-DIC: a new method for improved stress field measurements at the micrometer scale. AB - A better understanding of the effective mechanical behavior of polycrystalline materials requires an accurate knowledge of the behavior at a scale smaller than the grain size. The X-ray Laue microdiffraction technique available at beamline BM32 at the European Synchrotron Radiation Facility is ideally suited for probing elastic strains (and associated stresses) in deformed polycrystalline materials with a spatial resolution smaller than a micrometer. However, the standard technique used to evaluate local stresses from the distortion of Laue patterns lacks accuracy for many micromechanical applications, mostly due to (i) the fitting of Laue spots by analytical functions, and (ii) the necessary comparison of the measured pattern with the theoretical one from an unstrained reference specimen. In the present paper, a new method for the analysis of Laue images is presented. A Digital Image Correlation (DIC) technique, which is essentially insensitive to the shape of Laue spots, is applied to measure the relative distortion of Laue patterns acquired at two different positions on the specimen. The new method is tested on an in situ deformed Si single-crystal, for which the prescribed stress distribution has been calculated by finite-element analysis. It is shown that the new Laue-DIC method allows determination of local stresses with a strain resolution of the order of 10(-5). PMID- 26134803 TI - In situ hydrogen loading on zirconium powder. AB - For the first time, various hydride phases in a zirconium-hydrogen system have been prepared in a high-energy synchrotron X-ray radiation beamline and their transformation behaviour has been studied in situ. First, the formation and dissolution of hydrides in commercially pure zirconium powder were monitored in real time during hydrogenation and dehydrogenation, then whole pattern crystal structure analysis such as Rietveld and Pawley refinements were performed. All commonly reported low-pressure phases presented in the Zr-H phase diagram are obtained from a single experimental arrangement. PMID- 26134804 TI - Distinct effect of xenobiotics on the metal-binding properties of protein molecules. AB - The X-ray standing-wave method was applied to study the elemental composition and molecular organization of ordered protein films of alkaline phosphatase exposed to different xenobiotics (drug compounds, lead). Binding of metal ions from triply distilled water to protein molecules has been experimentally observed. Definite differences in the arrangement of impurity metal ions in the films have been established. The considerable enhancement of protein-metal interactions is attributed to partial rearrangement of the protein native structure, induced by xenobiotics. PMID- 26134805 TI - High-accuracy X-ray absorption spectra from mM solutions of nickel (II) complexes with multiple solutions using transmission XAS. AB - A new approach is introduced for determining X-ray absorption spectroscopy (XAS) spectra on absolute and relative scales using multiple solutions with different concentrations by the characterization and correction of experimental systematics. This hybrid technique is a development of standard X-ray absorption fine structure (XAFS) along the lines of the high-accuracy X-ray extended range technique (XERT) but with applicability to solutions, dilute systems and cold cell environments. This methodology has been applied to determining absolute XAS of bis(N-n-propyl-salicylaldiminato) nickel(II) and bis(N-i-propyl salicylaldiminato) nickel(II) complexes with square planar and tetrahedral structures in 15 mM and 1.5 mM dilute solutions. It is demonstrated that transmission XAS from dilute systems can provide excellent X-ray absorption near edge structure (XANES) and XAFS spectra, and that transmission measurements can provide accurate measurement of subtle differences including coordination geometries. For the first time, (transmission) XAS of the isomers have been determined from low-concentration solutions on an absolute scale with a 1-5% accuracy, and with relative precision of 0.1% to 0.2% in the active XANES and XAFS regions after inclusion of systematic corrections. PMID- 26134806 TI - Picosecond-resolved X-ray absorption spectroscopy at low signal contrast using a hard X-ray streak camera. AB - A picosecond-resolving hard-X-ray streak camera has been in operation for several years at Sector 7 of the Advanced Photon Source (APS). Several upgrades have been implemented over the past few years to optimize integration into the beamline, reduce the timing jitter, and improve the signal-to-noise ratio. These include the development of X-ray optics for focusing the X-rays into the sample and the entrance slit of the streak camera, and measures to minimize the amount of laser light needed to generate the deflection-voltage ramp. For the latter, the photoconductive switch generating the deflection ramp was replaced with microwave power electronics. With these, the streak camera operates routinely at 88 MHz repetition rate, thus making it compatible with all of the APS fill patterns including use of all the X-rays in the 324-bunch mode. Sample data are shown to demonstrate the performance. PMID- 26134807 TI - Charge redistribution and a shortening of the Fe--As bond at the quantum critical point of SmO1-xFxFeAs. AB - Many researchers have pointed out that there is a quantum critical point (QCP) in the F-doped SmOFeAs system. In this paper, the electronic structure and local structure of the superconductive FeAs layer in SmO(1-x)FxFeAs as a function of the F-doping concentration have been investigated using Fe and As K-edge X-ray absorption spectroscopy. Experiments performed on the X-ray absorption near-edge structure showed that in the vicinity of the QCP the intensity of the pre-edge feature at the Fe-edge decreases continuously, while there is a striking rise of the shoulder-peak at the As edge, suggesting the occurrence of charge redistribution near the QCP. Further analysis on the As K-edge extended X-ray absorption fine structure demonstrated that the charge redistribution originates mostly from a shortening of the Fe-As bond at the QCP. An evident relationship between the mysterious QCP and the fundamental Fe-As bond was established, providing new insights on the interplay between QCP, charge dynamics and the local structural Fe-As bond in Fe-based superconductors. PMID- 26134808 TI - Energy spectra considerations for synchrotron radiotherapy trials on the ID17 bio medical beamline at the European Synchrotron Radiation Facility. AB - The aim of this study was to validate the kilovoltage X-ray energy spectrum on the ID17 beamline at the European Synchrotron Radiation Facility (ESRF). The purpose of such validation was to provide an accurate energy spectrum as the input to a computerized treatment planning system, which will be used in synchrotron microbeam radiotherapy trials at the ESRF. Calculated and measured energy spectra on ID17 have been reported previously but recent additions and safety modifications to the beamline for veterinary trials warranted a fresh investigation. The authors used an established methodology to compare X-ray attenuation measurements in copper sheets (referred to as half value layer measurements in the radiotherapy field) with the predictions of a theoretical model. A cylindrical ionization chamber in air was used to record the relative attenuation of the X-ray beam intensity by increasing thicknesses of high-purity copper sheets. The authors measured the half value layers in copper for two beamline configurations, which corresponded to differing spectral conditions. The authors obtained good agreement between the measured and predicted half value layers for the two beamline configurations. The measured first half value layer was 1.754 +/- 0.035 mm Cu and 1.962 +/- 0.039 mm Cu for the two spectral conditions, compared with theoretical predictions of 1.763 +/- 0.039 mm Cu and 1.984 +/- 0.044 mm Cu, respectively. The calculated mean energies for the two conditions were 105 keV and 110 keV and there was not a substantial difference in the calculated percentage depth dose curves in water between the different spectral conditions. The authors observed a difference between their calculated energy spectra and the spectra previously reported by other authors, particularly at energies greater than 100 keV. The validation of the beam spectrum by the copper half value layer measurements means the authors can provide an accurate spectrum as an input to a treatment planning system for the forthcoming veterinary trials of microbeam radiotherapy to spontaneous tumours in cats and dogs. PMID- 26134809 TI - Real-space multiple-scattering Hubbard model calculations for d- and f-state materials. AB - Calculations are presented of the electronic structure and X-ray spectra of materials with correlated d- and f-electron states based on the Hubbard model, a real-space multiple-scattering formalism and a rotationally invariant local density approximation. Values of the Hubbard parameter are calculated ab initio using the constrained random-phase approximation. The combination of the real space Green's function with Hubbard model corrections provides an efficient approach to describe localized correlated electron states in these systems, and their effect on core-level X-ray spectra. Results are presented for the projected density of states and X-ray absorption spectra for transition metal- and lanthanide-oxides. Results are found to be in good agreement with experiment. PMID- 26134810 TI - Live small-animal X-ray lung velocimetry and lung micro-tomography at the Australian Synchrotron Imaging and Medical Beamline. AB - The high flux and coherence produced at long synchrotron beamlines makes them well suited to performing phase-contrast X-ray imaging of the airways and lungs of live small animals. Here, findings of the first live-animal imaging on the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron are reported, demonstrating the feasibility of performing dynamic lung motion measurement and high-resolution micro-tomography. Live anaesthetized mice were imaged using 30 keV monochromatic X-rays at a range of sample-to-detector propagation distances. A frame rate of 100 frames s(-1) allowed lung motion to be determined using X-ray velocimetry. A separate group of humanely killed mice and rats were imaged by computed tomography at high resolution. Images were reconstructed and rendered to demonstrate the capacity for detailed, user-directed display of relevant respiratory anatomy. The ability to perform X-ray velocimetry on live mice at the IMBL was successfully demonstrated. High-quality renderings of the head and lungs visualized both large structures and fine details of the nasal and respiratory anatomy. The effect of sample-to-detector propagation distance on contrast and resolution was also investigated, demonstrating that soft tissue contrast increases, and resolution decreases, with increasing propagation distance. This new capability to perform live-animal imaging and high-resolution micro tomography at the IMBL enhances the capability for investigation of respiratory diseases and the acceleration of treatment development in Australia. PMID- 26134811 TI - Quantitative phase retrieval in X-ray Zernike phase contrast microscopy. AB - In recent years, increasing attention has been devoted to X-ray phase contrast imaging, since it can provide high-contrast images by using phase variations. Among the different existing techniques, Zernike phase contrast microscopy is one of the most popular phase-sensitive techniques for investigating the fine structure of the sample at high spatial resolution. In X-ray Zernike phase contrast microscopy, the image contrast is indeed a mixture of absorption and phase contrast. Therefore, this technique just provides qualitative information on the object, which makes the interpretation of the image difficult. In this contribution, an approach is proposed for quantitative phase retrieval in X-ray Zernike phase contrast microscopy. By shifting the phase of the direct light by pi/2 and 3pi/2, two images of the same object are measured successively. The phase information of the object can then be quantitatively retrieved by a proper combination of the measured images. Numerical experiments were carried out and the results confirmed the feasibility of the proposed method. It is expected that the proposed method will find widespread applications in biology, materials science and so on. PMID- 26134812 TI - Characteristics of Friedel pairs and diffraction contrast tomography with non perpendicular rotation axis. AB - The characteristics of Friedel pairs in diffraction contrast tomography (DCT) are studied in the condition that the rotation axis of the sample is not exactly perpendicular to the incident X-ray direction. For the rotation axis approximately aligned along the vertical direction, the Friedel pairs close to the horizontal plane are insensitive to the non-perpendicularity of the rotation axis, and can be used to refine the sample-to-detector distance and X-ray energy, while the Friedel pairs close to the vertical direction are sensitive to the non perpendicularity of the rotation axis, and can be used to determine the rotation axis orientation. The correct matching proportion of Friedel pairs decreases with increasing non-perpendicularity of the rotation axis. A method of data processing considering rotation axis misalignment is proposed, which significantly increases the correct matching and indexing proportions of the diffraction spots. A pure aluminium polycrystalline sample is investigated using DCT at beamline 4W1A of Beijing Synchrotron Radiation Facility. Based on the analysis of Friedel pairs, the sample-to-detector distance and X-ray energy are refined to be 8.67 mm and 20.04 keV, respectively. The non-perpendicular angle of the rotation axis is calculated to be 0.10 degrees . With these refined geometric parameters, the matching proportion of the spatial position of diffraction spots is 90.62%. Three dimensional reconstruction of the sample with 13 grains is realised using the algebraic reconstruction technique. It is demonstrated that the precise correction of the orientation of the sample rotation axis is effective in DCT suffering from rotation axis misalignment, and the higher accuracy in determining the rotation axis is expected to improve the reconstruction precision of grains. PMID- 26134813 TI - Single-image phase retrieval using an edge illumination X-ray phase-contrast imaging setup. AB - A method is proposed which enables the retrieval of the thickness or of the projected electron density of a sample from a single input image acquired with an edge illumination phase-contrast imaging setup. The method assumes the case of a quasi-homogeneous sample, i.e. a sample with a constant ratio between the real and imaginary parts of its complex refractive index. Compared with current methods based on combining two edge illumination images acquired in different configurations of the setup, this new approach presents advantages in terms of simplicity of acquisition procedure and shorter data collection time, which are very important especially for applications such as computed tomography and dynamical imaging. Furthermore, the fact that phase information is directly extracted, instead of its derivative, can enable a simpler image interpretation and be beneficial for subsequent processing such as segmentation. The method is first theoretically derived and its conditions of applicability defined. Quantitative accuracy in the case of homogeneous objects as well as enhanced image quality for the imaging of complex biological samples are demonstrated through experiments at two synchrotron radiation facilities. The large range of applicability, the robustness against noise and the need for only one input image suggest a high potential for investigations in various research subjects. PMID- 26134814 TI - Simultaneous dual-energy X-ray stereo imaging. AB - Dual-energy or K-edge imaging is used to enhance contrast between two or more materials in an object and is routinely realised by acquiring two separate X-ray images each at different X-ray wavelength. On a broadband synchrotron source an imaging system to acquire the two images simultaneously was realised. The single shot approach allows dual-energy and stereo imaging to be applied to dynamic systems. Using a Laue-Bragg crystal splitting scheme, the X-ray beam was split into two and the two beam branches could be easily tuned to either the same or to two different wavelengths. Due to the crystals' mutual position, the two beam branches intercept each other under a non-zero angle and create a stereoscopic setup. PMID- 26134815 TI - Local strain and defects in silicon wafers due to nanoindentation revealed by full-field X-ray microdiffraction imaging. AB - Quantitative characterization of local strain in silicon wafers is critical in view of issues such as wafer handling during manufacturing and strain engineering. In this work, full-field X-ray microdiffraction imaging using synchrotron radiation is employed to investigate the long-range distribution of strain fields in silicon wafers induced by indents under different conditions in order to simulate wafer fabrication damage. The technique provides a detailed quantitative mapping of strain and defect characterization at the micrometer spatial resolution and holds some advantages over conventional methods. PMID- 26134816 TI - 3D imaging of a rice pollen grain using transmission X-ray microscopy. AB - For the first time, the three-dimensional (3D) ultrastructure of an intact rice pollen cell has been obtained using a full-field transmission hard X-ray microscope operated in Zernike phase contrast mode. After reconstruction and segmentation from a series of projection images, complete 3D structural information of a 35 um rice pollen grain is presented at a resolution of ~100 nm. The reconstruction allows a clear differentiation of various subcellular structures within the rice pollen grain, including aperture, lipid body, mitochondrion, nucleus and vacuole. Furthermore, quantitative information was obtained about the distribution of cytoplasmic organelles and the volume percentage of each kind of organelle. These results demonstrate that transmission X-ray microscopy can be quite powerful for non-destructive investigation of 3D structures of whole eukaryotic cells. PMID- 26134817 TI - Methodological challenges of optical tweezers-based X-ray fluorescence imaging of biological model organisms at synchrotron facilities. AB - Recently, a radically new synchrotron radiation-based elemental imaging approach for the analysis of biological model organisms and single cells in their natural in vivo state was introduced. The methodology combines optical tweezers (OT) technology for non-contact laser-based sample manipulation with synchrotron radiation confocal X-ray fluorescence (XRF) microimaging for the first time at ESRF-ID13. The optical manipulation possibilities and limitations of biological model organisms, the OT setup developments for XRF imaging and the confocal XRF related challenges are reported. In general, the applicability of the OT-based setup is extended with the aim of introducing the OT XRF methodology in all research fields where highly sensitive in vivo multi-elemental analysis is of relevance at the (sub)micrometre spatial resolution level. PMID- 26134818 TI - Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity. AB - Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, 'Elettra', Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma. PMID- 26134819 TI - MISTRAL: a transmission soft X-ray microscopy beamline for cryo nano-tomography of biological samples and magnetic domains imaging. AB - The performance of MISTRAL is reported, the soft X-ray transmission microscopy beamline at the ALBA light source (Barcelona, Spain) which is primarily dedicated to cryo soft X-ray tomography (cryo-SXT) for three-dimensional visualization of whole unstained cells at spatial resolutions down to 30 nm (half pitch). Short acquisition times allowing for high-throughput and correlative microscopy studies have promoted cryo-SXT as an emerging cellular imaging tool for structural cell biologists bridging the gap between optical and electron microscopy. In addition, the beamline offers the possibility of imaging magnetic domains in thin magnetic films that are illustrated here with an example. PMID- 26134820 TI - Optical design and multi-length-scale scanning spectro-microscopy possibilities at the Nanoscopium beamline of Synchrotron Soleil. AB - The Nanoscopium 155 m-long beamline of Synchrotron Soleil is dedicated to scanning hard X-ray nanoprobe techniques. Nanoscopium aims to reach <=100 nm resolution in the 5-20 keV energy range for routine user experiments. The beamline design tackles the tight stability requirements of such a scanning nanoprobe by creating an overfilled secondary source, implementing all horizontally reflecting main beamline optics, applying high mechanical stability equipment and constructing a dedicated high-stability building envelope. Multi technique scanning imaging and tomography including X-ray fluorescence spectrometry and spectro-microscopy, absorption, differential phase and dark field contrasts are implemented at the beamline in order to provide simultaneous information on the elemental distribution, speciation and sample morphology. This paper describes the optical concept and the first measured performance of the Nanoscopium beamline followed by the hierarchical length-scale multi-technique imaging experiments performed with dwell times down to 3 ms per pixel. PMID- 26134821 TI - Assessment of freeware programs for the reconstruction of tomography datasets obtained with a monochromatic synchrotron-based X-ray source. AB - Synchrotron-based in-line phase-contrast computed tomography (PC-CT) allows soft tissue to be imaged with sub-gross resolution and has potential to be used as a diagnostic tool. The reconstruction and processing of in-line PC-CT datasets is a computationally demanding task; thus, an efficient and user-friendly software program is desirable. Four freeware programs (NRecon, PITRE, H-PITRE and Athabasca Recon) were compared for the availability of features such as dark- and flat-field calibration, beam power normalization, ring artifact removal, and alignment tools for optimizing image quality. An in-line PC-CT projection dataset (3751 projections, 180 degrees rotation, 10.13 mm * 0.54 mm) was collected from a formalin-fixed canine prostate at the Biomedical Imaging and Therapy Bending Magnet (BMIT-BM) beamline of the Canadian Light Source. This dataset was processed with each of the four software programs and usability of the program was evaluated. Efficiency was assessed by how each program maximized computer processing power during computation. Athabasca Recon had the least-efficient memory usage, least user-friendly interface, and lacked a ring artifact removal feature. NRecon, PITRE and H-PITRE produced similar quality images, but the Athabasca Recon reconstruction suffered from the lack of a native ring remover algorithm. The 64-bit version of NRecon uses GPU (graphics processor unit) memory for accelerated processing and is user-friendly, but does not provide necessary parameters for in-line PC-CT data, such as dark-field and flat-field correction and beam power normalization. PITRE has many helpful features and tools, but lacks a comprehensive user manual and help section. H-PITRE is a condensed version of PITRE and maximizes computer memory for efficiency. To conclude, NRecon has fewer imaging processing tools than PITRE and H-PITRE, but is ideal for less experienced users due to a simple user interface. Based on the quality of reconstructed images, efficient use of computer memory and parameter availability, H-PITRE was the preferred of the four programs compared. PMID- 26134823 TI - International students' experience of a western medical school: a mixed methods study exploring the early years in the context of cultural and social adjustment compared to students from the host country. AB - BACKGROUND: Few studies have addressed the challenges associated with international students as they adapt to studying medicine in a new host country. Higher level institutions have increasing numbers of international students commencing programmes. This paper explores the experiences of a cohort of students in the early years of medical school in Ireland, where a considerable cohort are from an international background. METHODS: A mixed exploratory sequential study design was carried out with medical students in the preclinical component of a five year undergraduate programme. Data for the qualitative phase was collected through 29 semi-structured interviews using the peer interview method. Thematic analysis from this phase was incorporated to develop an online questionnaire combined with components of the Student Adaptation to College Questionnaire and Student Integration Questionnaire. First year students were anonymously surveyed online. The Mokken Scaling procedure was used to investigate the students' experiences, both positive and negative. RESULTS: Three main themes are identified; social adjustment, social alienation and cultural alienation. The response rate for the survey was 49% (467 Respondents). The Mokken Scaling method identified the following scales (i) Positive experience of student life; (ii) Social alienation, which comprised of negative items about feeling lonely, not fitting in, being homesick and (iii) Cultural alienation, which included the items of being uncomfortable around cultural norms of dress and contact between the sexes. With the threshold set to H = 0.4. Subscales of the positive experiences of student life scale are explored further. CONCLUSIONS: Overall student adjustment to a western third level college was good. Students from regions where cultural distance is greatest reported more difficulties in adjusting. Students from these regions also demonstrate very good adaptation. Some students from the host country and more similar cultural backgrounds were also struggling. Acculturation is more complex than being associated with cultural distance and worthy of further exploration. PMID- 26134824 TI - TLR7 and TLR8 expression increases tumor cell proliferation and promotes chemoresistance in human pancreatic cancer. AB - Chronic inflammation as an important epigenetic and environmental factor for putative tumorigenesis and tumor progression may be associated with specific activation of Toll-like receptors (TLR). Recently, carcinogenesis has been suggested to be dependent on TLR7 signaling. In the present study, we determined the role of both TLR7 and TLR8 expression and signaling in tumor cell proliferation and chemoresistance in pancreatic cancer. Expression of TLR7/TLR8 in UICC stage I-IV pancreatic cancer, chronic pancreatitis, normal pancreatic tissue and human pancreatic (PANC1) cancer cell line was examined. For in vitro/in vivo studies TLR7/TLR8 overexpressing PANC1 cell lines were generated and analyzed for effects of (un-)stimulated TLR expression on tumor cell proliferation and chemoresistance. TLR expression was increased in pancreatic cancer, with stage-dependent upregulation in advanced tumors, compared to earlier stages and chronic pancreatitis. Stimulation of TLR7/TLR8 overexpressing PANC1 cells resulted in elevated NF-kappaB and COX-2 expression, increased cancer cell proliferation and reduced chemosensitivity. More importantly, TLR7/TLR8 expression increased tumor growth in vivo. Our data demonstrate a stage-dependent upregulation of both TLR7 and TLR8 expression in pancreatic cancer. Functional analysis in human pancreatic cancer cells point to a significant role of both TLRs in chronic inflammation-mediated TLR7/TLR8 signaling leading to tumor cell proliferation and chemoresistance. PMID- 26134826 TI - Melatonin increases intracellular calcium in the liver, muscle, white adipose tissues and pancreas of diabetic obese rats. AB - Melatonin, a widespread substance with antioxidant and anti-inflammatory properties, has been found to act as an antidiabetic agent in animal models, regulating the release and action of insulin. However, the molecular bases of this antidiabetic action are unknown, limiting its application in humans. Several studies have recently shown that melatonin can modify calcium (Ca(2+)) in diabetic animals, and Ca(2+) has been reported to be involved in glucose homeostasis. The objective of the present study was to assess whether the antidiabetic effect of chronic melatonin at pharmacological doses is established via Ca(2+) regulation in different tissues in an animal model of obesity-related type 2 diabetes, using Zucker diabetic fatty (ZDF) rats and their lean littermates, Zucker lean (ZL) rats. After the treatments, flame atomic absorption spectrometry was used to determine Ca(2+) levels in the liver, muscle, main types of internal white adipose tissue, subcutaneous lumbar fat, pancreas, brain, and plasma. This study reports for the first time that chronic melatonin administration (10 mg per kg body weight per day for 6 weeks) increases Ca(2+) levels in muscle, liver, different adipose tissues, and pancreas in ZDF rats, although there were no significant changes in their brain or plasma Ca(2+) levels. We propose that this additional peripheral dual action mechanism underlies the improvement in insulin sensitivity and secretion previously documented in samples from the same animals. According to these results, indoleamine may be a potential candidate for the treatment of type 2 diabetes mellitus associated with obesity. PMID- 26134825 TI - Decreased Expression of MiRNA-204-5p Contributes to Glioma Progression and Promotes Glioma Cell Growth, Migration and Invasion. AB - Gliomas are the most common malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotype. Although increasing evidence indicated that the deregulation of microRNAs (miRNAs) contributes to tumorigenesis and invasion, little is known about the roles of miR-204-5p in human gliomas. In the present study, the expression of miR-204-5p in clinical glioma tissues was measured by qRT-PCR. The effects of miR-204-5p on glioma cell growth and metastasis were examined by overexpressing or inhibiting miR-204-5p. We found that the expression level of miR-204-5p was significantly reduced in clinical glioma tissues compared with normal brain tissues. Moreover, we revealed that the introduction of miR-204-5p dramatically suppressed glioma cell growth, migration and invasion. Furthermore, mechanistic investigations revealed that RAB22A, a member of the RAS oncogene family, is a direct functional target of miR 204-5p in gliomas. In vivo, restoring miR-204-5p expression in glioma cells suppressed tumorigenesis and increased overall host survival. Our findings suggest that miR-204-5p is a cancer suppressor miRNA and overexpression of miR 204-5p is a novel glioma treatment strategy. PMID- 26134827 TI - Assessment of Allergy to Milk, Egg, Cod, and Wheat in Swedish Schoolchildren: A Population Based Cohort Study. AB - OBJECTIVES: Knowledge about the prevalence of allergies to foods in childhood and adolescence is incomplete. The purpose of this study was to investigate the prevalence of allergies to milk, egg, cod, and wheat using reported data, clinical examinations, and double-blind placebo-controlled food challenges, and to describe the phenotypes of reported food hypersensitivity in a cohort of Swedish schoolchildren. METHODS: In a population-based cohort of 12-year-old children, the parents of 2612 (96% of invited) completed a questionnaire. Specific IgE antibodies to foods were analyzed in a random sample (n=695). Children reporting complete avoidance of milk, egg, cod, or wheat due to perceived hypersensitivity and without physician-diagnosed celiac disease were invited to undergo clinical examination that included specific IgE testing, a celiac screening test, and categorization into phenotypes of food hypersensitivity according to preset criteria. Children with possible food allergy were further evaluated with double-blind challenges. RESULTS: In this cohort, the prevalence of reported food allergy to milk, egg, cod, or wheat was 4.8%. Food allergy was diagnosed in 1.4% of the children after clinical evaluation and in 0.6% following double-blind placebo-controlled food challenge. After clinical examination, children who completely avoided one or more essential foods due to perceived food hypersensitivity were categorized with the following phenotypes: allergy (29%), outgrown allergy (19%), lactose intolerance (40%), and unclear (12%). CONCLUSIONS: There was a high discrepancy in the prevalence of allergy to milk, egg, cod and wheat as assessed by reported data, clinical evaluation, and double-blind food challenges. Food hypersensitivity phenotyping according to preset criteria was helpful for identifying children with food allergy. PMID- 26134828 TI - Pros and cons of methylation-based enrichment methods for ancient DNA. AB - The recent discovery that DNA methylation survives in fossil material provides an opportunity for novel molecular approaches in palaeogenomics. Here, we apply to ancient DNA extracts the probe-independent Methylated Binding Domains (MBD)-based enrichment method, which targets DNA molecules containing methylated CpGs. Using remains of a Palaeo-Eskimo Saqqaq individual, woolly mammoths, polar bears and two equine species, we confirm that DNA methylation survives in a variety of tissues, environmental contexts and over a large temporal range (4,000 to over 45,000 years before present). MBD enrichment, however, appears principally biased towards the recovery of CpG-rich and long DNA templates and is limited by the fast post-mortem cytosine deamination rates of methylated epialleles. This method, thus, appears only appropriate for the analysis of ancient methylomes from very well preserved samples, where both DNA fragmentation and deamination have been limited. This work represents an essential step toward the characterization of ancient methylation signatures, which will help understanding the role of epigenetic changes in past environmental and cultural transitions. PMID- 26134829 TI - Challenges for group leaders working with families dealing with early psychosis: a qualitative study. AB - BACKGROUND: Family work is one of the best researched psychosocial interventions for patients with chronic psychosis. However, family work is less studied for patients with a first episode psychosis and the studies have revealed contradicting results. To our knowledge, no previous studies have examined qualitatively group leaders' experiences with family work. In the present study we wanted to explore challenges faced by mental health professionals working as group leaders for family interventions with first episode psychosis patients. METHOD: A qualitative exploratory study was carried out based on digitally recorded in-depth interviews and a focus group interview with nine experienced mental health professionals. The interviews were transcribed in a slightly modified verbatim mode and analysed by systematic text condensation. RESULTS: Challenges faced by group leaders was classified into six categories: (1) Motivating patients to participate, encouraging potential participants was demanding and time-consuming; (2) Selecting participants by identifying those who can form a functional group and benefit from the intervention; (3) Choosing group format to determine whether a single or multi-family group is best for the participants; (4) Preserving patient independence, while also encouraging them to participate in the intervention; (5) Adherence to the protocol, while customizing adjustments as needed; (6) Fostering good problem-solving by creating a fertile learning environment and choosing the most appropriate problem to solve. CONCLUSIONS: Group leaders face challenges related to recruitment and selection of participants for family work, as well as in conducting sessions. Awareness of these challenges could help health professionals more specifically to tailor the intervention to the specific needs of patients and their families. PMID- 26134830 TI - Skin mucus proteome of gilthead sea bream: A non-invasive method to screen for welfare indicators. AB - In teleosts, the skin mucus is the first physical barrier against physical and chemical attacks. It contains components related to metabolism, environmental influences and nutritional status. Here, we study mucus and composition based on a proteome map of soluble epidermal mucus proteins obtained by 2D-electrophoresis in gilthead sea bream, Sparus aurata. Over 1300 spots were recorded and the 100 most abundant were further analysed by LC-MS/MS and identified by database retrieval; we also established the related specific biological processes by Gene Ontology enrichment. Sixty-two different proteins were identified and classified in 12 GO-groups and into three main functions: structural, metabolic and protection-related. Several of the proteins can be used as targets to determine fish physiological status: actins and keratins, and especially their catabolic products, in the structural functional group; glycolytic enzymes and ubiquitin/proteasome-related proteins in the metabolic functional group; and heat shock proteins, transferrin and hemopexins, in the protection-related group. This study analyses fish mucus, a potential non-invasive tool for characterising fish status, beyond defence capacities, and we postulate some putative candidates for future studies along similar lines. PMID- 26134831 TI - Early Detection of Physical Activity for People With Type 1 Diabetes Mellitus. AB - BACKGROUND: Early detection of exercise in individuals with type 1 diabetes mellitus (T1DM) may allow changes in therapy to prevent hypoglycemia. Currently there is limited experience with automated methods that detect the onset and end of exercise in this population. We sought to develop a novel method to quickly and reliably detect the onset and end of exercise in these individuals before significant changes in blood glucose (BG) occur. METHODS: Sixteen adults with T1DM were studied as outpatients using a diary, accelerometer, heart rate monitor, and continuous glucose monitor for 2 days. These data were used to develop a principal component analysis based exercise detection method. Subjects also performed 60 and 30 minute exercise sessions at 30% and 50% predicted heart rate reserve (HRR), respectively. The detection method was applied to the exercise sessions to determine how quickly the detection of start and end of exercise occurred relative to change in BG. RESULTS: Mild 30% HRR and moderate 50% HRR exercise onset was identified in 6 +/- 3 and 5 +/- 2 (mean +/- SD) minutes, while completion was detected in 3 +/- 8 and 6 +/- 5 minutes, respectively. BG change from start of exercise to detection time was 1 +/- 6 and 1 +/- 3 mg/dL, and, from the end of exercise to detection time was 6 +/- 4 and 17 +/- 13 mg/dL, respectively, for the 2 exercise sessions. False positive and negative ratios were 4 +/- 2% and 21 +/- 22%. CONCLUSIONS: The novel method for exercise detection identified the onset and end of exercise in approximately 5 minutes, with an average BG change of only -6 mg/dL. PMID- 26134832 TI - Modeling the Physiological Factors Affecting Glucose Sensor Function in Vivo. AB - For implantable sensors to become a more viable option for continuous glucose monitoring strategies, they must be able to persist in vivo for periods longer than the 3- to 7-day window that is the current industry standard. Recent studies have attributed such limited performance to tissue reactions resulting from implantation. While in vivo biocompatibility studies have provided much in the way of understanding histology surrounding an implanted sensor, little is known about how each constituent of the foreign body response affects sensor function. Due to the ordered composition and geometry of implant-associated tissue reactions, their effects on sensor function may be computationally modeled and analyzed in a way that would be prohibitive using in vivo studies. This review both explains how physiologically accurate computational models of implant associated tissue reaction can be designed and shows how they have been utilized thus far. Going forward, these in silico models of implanted sensor behavior may soon complement in vivo studies to provide valuable information for improved sensor designs. PMID- 26134833 TI - A Statistical Analysis of a Traffic-Light Food Rating System to Promote Healthy Nutrition and Body Weight. AB - BACKGROUND: Restaurant eating while optimizing nutrition and maintaining a healthy weight is challenging. Even when nutritional information is available, consumers often consider only calories. A quick and easy method to rate both caloric density and nutrition is an unmet need. A food rating system created to address that need is assessed in this study. METHODS: The food rating system categorizes food items into 3 color-coded categories: most healthy (green), medium healthy (yellow), or least healthy (red) based on calorie density and general nutritional quality from national guidelines. Nutritional information was downloaded from 20 popular fast-food chains. Nutritional assessments and the 3 color coded categories were compared using the Wilcoxon and Median tests to demonstrate the significance of nutrition differences. RESULTS: Green foods were significantly lower than yellow foods, which in turn were significantly lower than red foods, for calories and calories from fat, in addition to content of total fat, saturated fat and carbohydrates per 100 g serving weight (all P < .02). The green foods had significantly lower cholesterol than the yellow (P = .0006) and red (P < .0001) foods. Yellow foods had less sugar than red foods (P < .0001). Yellow foods were significantly higher in dietary fiber than red foods (P = .001). CONCLUSION: The food rating color-coded system identifies food items with superior nutrition, and lower caloric density. The smartphone app, incorporating the system, has the potential to improve nutrition; reduce the risk of developing diabetes, hypertension, heart disease, and stroke; and improve public health. PMID- 26134834 TI - Sensitivity of the Predictive Hypoglycemia Minimizer System to the Algorithm Aggressiveness Factor. AB - BACKGROUND: The Predictive Hypoglycemia Minimizer System ("Hypo Minimizer"), consisting of a zone model predictive controller (the "controller") and a safety supervision module (the "safety module"), aims to mitigate hypoglycemia by preemptively modulating insulin delivery based on continuous glucose monitor (CGM) measurements. The "aggressiveness factor," a pivotal variable in the system, governs the speed and magnitude of the controller's insulin dosing characteristics in response to changes in CGM levels. METHODS: Twelve adults with type 1 diabetes were studied in closed-loop in a clinical research center for approximately 24 hours. This analysis focused primarily on the effect of the aggressiveness factor on the automated insulin-delivery characteristics of the controller, and secondarily on the glucose control results. RESULTS: As aggressiveness increased from "conservative" to "medium" to "aggressive," the controller recommended less insulin (-3.3% vs -14.4% vs -19.5% relative to basal) with a higher frequency (5.3% vs 14.4% vs 20.3%) during the critical times when the CGM was reading 90-120 mg/dl and decreasing. Blood glucose analyses indicated that the most aggressive setting resulted in the most desirable combination of the least time spent <70 mg/dl and the most time spent 70-180 mg/dl, particularly in the overnight period. Hyperglycemia, diabetic ketoacidosis, or severe hypoglycemia did not occur with any of the aggressiveness values. CONCLUSION: The Hypo Minimizer's controller took preemptive action to prevent hypoglycemia based on predicted changes in CGM glucose levels. The most aggressive setting was quickest to take action to reduce insulin delivery below basal and achieved the best glucose metrics. PMID- 26134835 TI - Using Continuous Glucose Monitoring Data and Detrended Fluctuation Analysis to Determine Patient Condition: A Review. AB - Patients admitted to critical care often experience dysglycemia and high levels of insulin resistance, various intensive insulin therapy protocols and methods have attempted to safely normalize blood glucose (BG) levels. Continuous glucose monitoring (CGM) devices allow glycemic dynamics to be captured much more frequently (every 2-5 minutes) than traditional measures of blood glucose and have begun to be used in critical care patients and neonates to help monitor dysglycemia. In an attempt to obtain a better insight relating biomedical signals and patient status, some researchers have turned toward advanced time series analysis methods. In particular, Detrended Fluctuation Analysis (DFA) has been a topic of many recent studies in to glycemic dynamics. DFA investigates the "complexity" of a signal, how one point in time changes relative to its neighboring points, and DFA has been applied to signals like the inter-beat interval of human heartbeat to differentiate healthy and pathological conditions. Analyzing the glucose metabolic system with such signal processing tools as DFA has been enabled by the emergence of high quality CGM devices. However, there are several inconsistencies within the published work applying DFA to CGM signals. Therefore, this article presents a review and a "how-to" tutorial of DFA, and in particular its application to CGM signals to ensure the methods used to determine complexity are used correctly and so that any relationship between complexity and patient outcome is robust. PMID- 26134836 TI - Comparison of Subcutaneous Regular Insulin and Lispro Insulin in Diabetics Receiving Continuous Nutrition: A Numerical Study. AB - BACKGROUND: Optimal management of non-critically ill patients with diabetes maintained on continuous enteral feeding (CEN) is poorly defined. Subcutaneous (SQ) lispro and SQ regular insulin were compared in a simulated type 1 and type 2 diabetic patient receiving CEN. METHOD: A glucose-insulin feedback mathematical model was employed to simulate type 1 and type 2 diabetic patients on CEN. Each patient received 25 SQ injections of regular insulin or insulin lispro, ranging from 0-6 U. Primary endpoints were the change in mean glucose concentration (MGC) and change in glucose variability (GV); hypoglycemic episodes were also reported. The model was first validated against patient data. RESULTS: Both SQ insulin preparations linearly decreased MGC, however, SQ regular insulin decreased GV whereas SQ lispro tended to increase GV. Hourly glucose concentration measurements were needed to capture the increase in GV. In the type 2 diabetic patient, "rebound hyperglycemia" occurred after SQ lispro was rapidly metabolized. Although neither SQ insulin preparation caused hypoglycemia, SQ lispro significantly lowered MGC compared to SQ regular insulin. Thus, it may be more likely to cause hypoglycemia. Analyses of the detailed glucose concentration versus time data suggest that the inferior performance of lispro resulted from its shorter duration of action. Finally, the effects of both insulin preparations persisted beyond their duration of actions in the type 2 diabetic patient. CONCLUSIONS: Subcutaneous regular insulin may be the short-acting insulin preparation of choice for this subset of diabetic patients. Clinical trial is required before a definitive recommendation can be made. PMID- 26134838 TI - New thorium(iv)-arsonates with a [Th8O13]6+ octanuclear core. AB - Three new octanuclear Th(iv) arsonates, namely [Th(8)(O)(L)(6)(HL)(6)(H(2)O)(12)].19.5H(2)O (1) (H(3)L = o-HO(3)S-C(6)H(4) AsO(3)H(2)), [Th(8)(O)(L)(6)(HL)(6)(H(2)O)(10)].17H(2)O (2) and [Th(8)(O)(L)(6)(HL)(6)(H(2)O)(5)].0.5H(2)O (3), with o-sulfophenylarsonic acid as the bridging ligand, have been prepared under hydrothermal conditions. Each complex contains [Th(8)O(13)](6+) octanuclear cluster cores composed of two [Th(4)O(6)](4+) units bridged by a MU(2)-oxo anion. The structure of compound features a 0D highly symmetric polynuclear cluster encapsulating the octanuclear core of [Th(8)O(13)](6+) which is further decorated by six L(3-) and six HL(2-) ligands. Compound 2 features one-dimensional chains along the b-axis in which the neighboring clusters similar to are bridged by a pair of sulfophenylarsonate ligands via M-O-S-O-M bridges. Compound 3 with chiral P2(1)2(1)2(1) features two dimensional cluster layers, in which each cluster connects with four neighbors via four M-O-S-O-M linkages. Compounds 2 and 3 display unusual broad green light emission bands at 523 nm (lambda(ex) = 320 nm) and 517 nm (lambda(ex) = 312 nm), respectively, which originate from the ligand-to-metal charge transfer (LMCT) transition. PMID- 26134837 TI - A practice-based randomized controlled trial to improve medication adherence among Latinos with hypertension: study protocol for a randomized controlled trial. AB - BACKGROUND: Latinos experience disproportionately higher rates of uncontrolled hypertension as compared to Blacks and Whites. While poor adherence is a major contributor to disparities in blood pressure control, data in Latino patients are scant. More importantly, translation of interventions to improve medication adherence in community-based primary care practices, where the majority of Latino patients receive their care is non-existent. METHODS: Using a randomized controlled design, this study evaluates the effectiveness of a culturally tailored, practice-based intervention compared to usual care on medication adherence, among 148 Latino patients with uncontrolled hypertension who are non adherent to their antihypertensive medications. Bilingual medical assistants trained as Health Coaches deliver the intervention using an electronic medical record system-embedded adherence script. Patients randomized to the intervention group receive patient-centered counseling with a Health Coach to develop individualized self-monitoring strategies to overcome barriers and improve adherence behaviors. Health Coach sessions are held biweekly for the first 3 months (6 sessions total) and then monthly for the remaining 3 months (3 sessions total). Patients randomized to the usual care group receive standard hypertension treatment recommendations as determined by their primary care providers. The primary outcome is the rate of medication adherence at 6 months. The secondary outcome is reduction in systolic and diastolic blood pressure at 6 months. DISCUSSION: If successful, findings from this study will provide salient information on the translation of culturally tailored, evidence-based interventions targeted at medication adherence and blood pressure control into practice-based settings for this high-risk population. TRIAL REGISTRATION: NCT01643473 on 16 July 2012. PMID- 26134839 TI - Conversion of cheese whey into poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by Haloferax mediterranei. AB - Haloferax mediterranei was cultivated in highly saline medium using cheese whey as the substrate for the production of poly(3-hydroxybutyrate-co-3 hydroxyvalerate), P(3HB-co-3HV). Acid hydrolysis provided a simple inexpensive method to obtain a cheese whey hydrolysate that was used for cultivation of H. mediterranei. Batch bioreactor cultivation of H. mediterranei resulted in the production of an active biomass concentration of 7.54 g L(-1) with a polymer content of 53%, and a volumetric productivity of 4.04 g L(-1) day(-1). Supplementation of the cultivation medium with micronutrients favored galactose consumption that was used for polymer synthesis after exhaustion of the available glucose. P(3HB-co-3HV) with a 3-hydroxyvalerate content of 1.5 mol% was extracted from the biomass by hypo-osmotic shock. The polymer presented a molecular mass of 4.4*10(5), with a polydispersity index of 1.5. This work demonstrated the feasibility of using cheese whey for the production of a value-added biopolymer with high volumetric productivity, by using a glucose- and galactose-rich substrate obtained by acid hydrolysis of cheese whey. The use of H. mediterranei as the producing strain avoids the need for strict sterility due to the culture's high salinity requirements and, also, allows for polymer extraction by simply contacting the biomass with water. PMID- 26134840 TI - Genetics of Primary Inherited Disorders of the Optic Nerve: Clinical Applications. AB - Inherited disorders of the optic nerve significantly impact vision in children and adults. The optic nerve disorders most commonly encountered clinically are glaucoma and primary optic neuropathy including Leber's hereditary optic neuropathy (LHON) and autosomal dominant or Kjer's optic atrophy. Current knowledge of the genetics of optic neuropathy and glaucoma makes it possible to test for mutations in disease-causing genes allowing for presymptomatic testing and risk assessment, and recent advances have revealed important disease mechanisms that may suggest potential therapeutic targets. In this perspective, we describe the current approaches and limitations to genetic testing for these disorders and provide an update on the development of gene-based therapies. PMID- 26134841 TI - Hepadnavirus Genome Replication and Persistence. AB - Hallmarks of the hepadnavirus replication cycle are the formation of covalently closed circular DNA (cccDNA) and the reverse transcription of a pregenomic RNA (pgRNA) in core particles leading to synthesis of the relaxed circular DNA (rcDNA) genome. cccDNA, the template for viral RNA transcription, is the basis for the persistence of these viruses in infected hepatocytes. In this review, we summarize the current state of knowledge on the mechanisms of hepadnavirus reverse transcription and the biochemical and structural properties of the viral reverse transcriptase (RT). We highlight important gaps in knowledge regarding cccDNA biosynthesis and stability. In addition, we discuss the impact of current antiviral therapies on viral persistence, particularly on cccDNA. PMID- 26134842 TI - Hepatitis D Virus: Introduction and Epidemiology. AB - Hepatitis D is caused by the hepatitis D virus (HDV), a unique RNA pathogen that requires the hepatitis B surface antigen (HBsAg) to infect. Hepatitis D is transmitted by the parenteral route. The main susceptible group is patients with chronic HBsAg infection who become superinfected with the virus. Hepatitis D occurs throughout the globe, but control of hepatitis B virus (HBV) in the last two decades has consistently diminished the circulation of HDV in industrialized countries. However, hepatitis D remains a medical issue for injecting drug users (IDUs), as well as immigrants from endemic HDV areas, who are reintroducing the infection in Europe. PMID- 26134843 TI - Initiation, Propagation, and Termination of Partial (Focal) Seizures. AB - The neurophysiological patterns that correlate with partial (focal) seizures are well defined in humans by standard electroencephalogram (EEG) and presurgical depth electrode recordings. Seizure patterns with similar features are reproduced in animal models of partial seizures and epilepsy. However, the network determinants that support interictal spikes, as well as the initiation, progression, and termination of seizures, are still elusive. Recent findings show that inhibitory networks are prominently involved at the onset of these seizures, and that extracellular changes in potassium contribute to initiate and sustain seizure progression. The end of a partial seizure correlates with an increase in network synchronization, which possibly involves both excitatory and inhibitory mechanisms. PMID- 26134844 TI - Simultaneous Determination of Underivatized Vitamin B1 and B6 in Whole Blood by Reversed Phase Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. AB - BACKGROUND: Vitamin B1 (thiamine-diphosphate) and B6 (pyridoxal-5'phosphate) are micronutrients. Analysis of these micronutrients is important to diagnose potential deficiency which often occurs in elderly people due to malnutrition, in severe alcoholism and in gastrointestinal compromise due to bypass surgery or disease. Existing High Performance Liquid Chromatography (HPLC) based methods include the need for derivatization and long analysis time. We developed an Ultra High Performance Liquid Chromatography Tandem Mass spectrometry (UHPLC-MS/MS) assay with internal standards for simultaneous measurement of underivatized thiamine-diphosphate and pyridoxal-5'phosphate without use of ion pairing reagent. METHODS: Whole blood, deproteinized with perchloric acid, containing deuterium labelled internal standards thiamine-diphosphate(thiazole-methyl-D3) and pyridoxal-5'phosphate(methyl-D3), was analyzed by UHPLC-MS/MS. The method was validated for imprecision, linearity, recovery and limit of quantification. Alternate (quantitative) method comparisons of the new versus currently used routine HPLC methods were established with Deming regression. RESULTS: Thiamine diphosphate and pyridoxal-5'phosphate were measured within 2.5 minutes instrumental run time. Limits of detection were 2.8 nmol/L and 7.8 nmol/L for thiamine-diphosphate and pyridoxal-5'phosphate respectively. Limit of quantification was 9.4 nmol/L for thiamine-diphosphate and 25.9 nmol/L for pyridoxal-5'phosphate. The total imprecision ranged from 3.5-7.7% for thiamine diphosphate (44-157 nmol/L) and 6.0-10.4% for pyridoxal-5'phosphate (30-130 nmol/L). Extraction recoveries were 101-102% +/- 2.5% (thiamine-diphosphate) and 98-100% +/- 5% (pyridoxal-5'phosphate). Deming regression yielded slopes of 0.926 and 0.990 in patient samples (n = 282) and national proficiency testing samples (n = 12) respectively, intercepts of +3.5 and +3 for thiamine-diphosphate (n = 282 and n = 12) and slopes of 1.04 and 0.84, intercepts of -2.9 and +20 for pyridoxal-5'phosphate (n = 376 and n = 12). CONCLUSION: The described UHPLC-MS/MS method allows simultaneous determination of underivatized thiamine-diphosphate and pyridoxal-5'phosphate in whole blood without intensive sample preparation. PMID- 26134845 TI - Closed-Loop Control of a Neuroprosthetic Hand by Magnetoencephalographic Signals. AB - OBJECTIVE: A neuroprosthesis using a brain-machine interface (BMI) is a promising therapeutic option for severely paralyzed patients, but the ability to control it may vary among individual patients and needs to be evaluated before any invasive procedure is undertaken. We have developed a neuroprosthetic hand that can be controlled by magnetoencephalographic (MEG) signals to noninvasively evaluate subjects' ability to control a neuroprosthesis. METHOD: Six nonparalyzed subjects performed grasping or opening movements of their right hand while the slow components of the MEG signals (SMFs) were recorded in an open-loop condition. The SMFs were used to train two decoders to infer the timing and types of movement by support vector machine and Gaussian process regression. The SMFs were also used to calculate estimated slow cortical potentials (eSCPs) to identify the origin of motor information. Finally, using the trained decoders, the subjects controlled a neuroprosthetic hand in a closed-loop condition. RESULTS: The SMFs in the open loop condition revealed movement-related cortical field characteristics and successfully inferred the movement type with an accuracy of 75.0 +/- 12.9% (mean +/- SD). In particular, the eSCPs in the sensorimotor cortex contralateral to the moved hand varied significantly enough among the movement types to be decoded with an accuracy of 76.5 +/- 10.6%, which was significantly higher than the accuracy associated with eSCPs in the ipsilateral sensorimotor cortex (58.1 +/- 13.7%; p = 0.0072, paired two-tailed Student's t-test). Moreover, another decoder using SMFs successfully inferred when the accuracy was the greatest. Combining these two decoders allowed the neuroprosthetic hand to be controlled in a closed loop condition. CONCLUSIONS: Use of real-time MEG signals was shown to successfully control the neuroprosthetic hand. The developed system may be useful for evaluating movement-related slow cortical potentials of severely paralyzed patients to predict the efficacy of invasive BMI. PMID- 26134846 TI - A streptozotocin-induced diabetic neuropathic pain model for static or dynamic mechanical allodynia and vulvodynia: validation using topical and systemic gabapentin. AB - Neuropathic vulvodynia is a state of vulval discomfort characterized by a burning sensation, diffuse pain, pruritus or rawness with an acute or chronic onset. Diabetes mellitus may cause this type of vulvar pain in several ways, so this study was conducted to evaluate streptozotocin-induced diabetes as a neuropathic pain model for vulvodynia in female rats. The presence of streptozotocin (50 mg/kg i.p.)-induced diabetes was initially verified by disclosure of pancreatic tissue degeneration, blood glucose elevation and body weight loss 5-29 days after a single treatment. Dynamic (shortened paw withdrawal latency to light brushing) and static (diminished von Frey filament threshold pressure) mechanical allodynia was then confirmed on the plantar foot surface. Subsequently, both static and dynamic vulvodynia was detected by application of the paradigm to the vulval region. Systemic gabapentin (75 mg/kg, i.p.) and topical gabapentin (10 % gel) were finally tested against allodynia and vulvodynia. Topical gabapentin and the control gel vehicle significantly increased paw withdrawal threshold in the case of the static allodynia model and also paw withdrawal latency in the model for dynamic allodynia when compared with the streptozotocin-pretreated group. Likewise, in the case of static and dynamic vulvodynia, there was a significant antivulvodynia effect of systemic and topical gabapentin treatment. These outcomes substantiate the value of this model not only for allodynia but also for vulvodynia, and this was corroborated by the findings not only with systemic but also with topical gabapentin. PMID- 26134847 TI - Serine Arginine-Rich Splicing Factor 1 (SRSF1) Contributes to the Transcriptional Activation of CD3zeta in Human T Cells. AB - T lymphocytes from many patients with systemic lupus erythematosus (SLE) express decreased levels of the T cell receptor (TCR)-associated CD3 zeta (zeta) signaling chain, a feature directly linked to their abnormal phenotype and function. Reduced mRNA expression partly due to defective alternative splicing, contributes to the reduced expression of CD3zeta chain. We previously identified by oligonucleotide pulldown and mass spectrometry approaches, the serine arginine rich splicing factor 1 (SRSF1) binding to the 3' untranslated region (UTR) of CD3zeta mRNA. We showed that SRSF1 regulates alternative splicing of the 3'UTR of CD3zeta to promote expression of the normal full length 3'UTR over an unstable splice variant in human T cells. In this study we show that SRSF1 regulates transcriptional activation of CD3zeta. Specifically, overexpression and silencing of SRSF1 respectively increases and decreases CD3zeta total mRNA and protein expression in Jurkat and primary T cells. Using promoter-luciferase assays, we show that SRSF1 enhances transcriptional activity of the CD3zeta promoter in a dose dependent manner. Chromatin immunoprecipitation assays show that SRSF1 is recruited to the CD3zeta promoter. These results indicate that SRSF1 contributes to transcriptional activation of CD3zeta. Thus our study identifies a novel mechanism whereby SRSF1 regulates CD3zeta expression in human T cells and may contribute to the T cell defect in SLE. PMID- 26134848 TI - An Integer Programming Formulation of the Minimum Common String Partition Problem. AB - We consider the problem of finding a minimum common string partition (MCSP) of two strings, which is an NP-hard problem. The MCSP problem is closely related to genome comparison and rearrangement, an important field in Computational Biology. In this paper, we map the MCSP problem into a graph applying a prior technique and using this graph, we develop an Integer Linear Programming (ILP) formulation for the problem. We implement the ILP formulation and compare the results with the state-of-the-art algorithms from the literature. The experimental results are found to be promising. PMID- 26134850 TI - Nerve transfers and neurotization in peripheral nerve injury, from surgery to rehabilitation. AB - Peripheral nerve injury (PNI) and recent advances in nerve reconstruction (such as neurotization with nerve transfers) have improved outcomes for patients suffering peripheral nerve trauma. The purpose of this paper is to bridge the gap between the electromyographer/clinical neurophysiologist and the peripheral nerve surgeon. Whereas the preceding literature focuses on either the basic science behind nerve injury and reconstruction, or the surgical options and algorithms, this paper demonstrates how electromyography is not just a 'decision tool' when deciding whether to operate but is also essential to all phases of PNI management including surgery and rehabilitation. The recent advances in the reconstruction and rehabilitation of PNI is demonstrated using case examples to assist the electromyographer to understand modern surgical techniques and the unique demands they ask from electrodiagnostic testing. PMID- 26134851 TI - A unique account of ALS in China: exploring ethnic heterogeneity. PMID- 26134849 TI - SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation. AB - The SAM domain and HD domain containing protein 1 (SAMHD1) inhibits retroviruses, DNA viruses and long interspersed element 1 (LINE-1). Given that in dividing cells, SAMHD1 loses its antiviral function yet still potently restricts LINE-1, we propose that, instead of blocking viral DNA synthesis by virtue of its dNTP triphosphohydrolase activity, SAMHD1 may exploit a different mechanism to control LINE-1. Here, we report a new activity of SAMHD1 in promoting cellular stress granule assembly, which correlates with increased phosphorylation of eIF2alpha and diminished eIF4A/eIF4G interaction. This function of SAMHD1 enhances sequestration of LINE-1 RNP in stress granules and consequent blockade to LINE-1 retrotransposition. In support of this new mechanism of action, depletion of stress granule marker proteins G3BP1 or TIA1 abrogates stress granule formation and overcomes SAMHD1 inhibition of LINE-1. Together, these data reveal a new mechanism for SAMHD1 to control LINE-1 by activating cellular stress granule pathway. PMID- 26134852 TI - Generation of stable cell line by using chitosan as gene delivery system. AB - Establishing stable cell lines are useful tools to study the function of various genes and silence or induce the expression of a gene of interest. Nonviral gene transfer is generally preferred to generate stable cell lines in the manufacturing of recombinant proteins. In this study, we aimed to establish stable recombinant HEK-293 cell lines by transfection of chitosan complexes preparing with pDNA which contain LacZ and GFP genes. Chitosan which is a cationic polymer was used as gene delivery system. Stable HEK-293 cell lines were established by transfection of cells with complexes which were prepared with chitosan and pVitro-2 plasmid vector that contains neomycin drug resistance gene, beta gal and GFP genes. The transfection efficiency was shown with GFP expression in the cells using fluorescence microscopy. Beta gal protein expression in stable cells was examined by beta-galactosidase assay as enzymatically and X-gal staining method as histochemically. Full complexation was shown in the above of 1/1 ratio in the chitosan/pDNA complexes. The highest beta-galactosidase activity was obtained with transfection of chitosan complexes. Beta gal gene expression was 15.17 ng/ml in the stable cells generated by chitosan complexes. In addition, intensive blue color was observed depending on beta gal protein expression in the stable cell line with X-gal staining. We established a stable HEK-293 cell line that can be used for recombinant protein production or gene expression studies by transfecting the gene of interest. PMID- 26134854 TI - Smoking is inversely related to cutaneous malignant melanoma: results of a meta analysis. PMID- 26134855 TI - One novel cis-element is essential for correct DYSFUNCTIONAL TAPETUM 1 (DYT1) expression in Arabidopsis thaliana. AB - KEY MESSAGE: We studied the function of DYT1 promoter, found the important sectors controlling specific expression of DYT1 , and identified a new cis element for further investigation of DYT1 upstream genes. DYT1 is a core regulatory gene for tapetum development in Arabidopsis thaliana. However, the mechanism leading to DYT1 tapetum-preferential expression is still unknown up to date. Here we employed promoter truncation and deletion assay to identify a 'CTCC' cis-element, which was essential for correct DYT1 expression within DYT1 promoter region. Through comparing truncated DYT1 promoter-driven GFP expression, the -481 to -513 bp region from the start point of transcription (SPT) of DYT1 was found indispensable for proper DYT1 expression. Further deletion assay around this region revealed that an approximate -468 bp 'CTCC' sequence deletion abolished normal DYT1 expression completely. Bioinformatics assay suggested that this 'CTCC' motif was potentially a novel DNA-recognition sequence, providing new clue for investigating relationship between DYT1 and its upstream genes. PMID- 26134856 TI - Parameters affecting frequency of CRISPR/Cas9 mediated targeted mutagenesis in rice. AB - KEY MESSAGE: Frequency of CRISPR/Cas9-mediated targeted mutagenesis varies depending on Cas9 expression level and culture period of rice callus. Recent reports have demonstrated that the CRISPR/Cas9 system can function as a sequence specific nuclease in various plant species. Induction of mutation in proliferating tissue during embryogenesis or in germline cells is a practical means of generating heritable mutations. In the case of plant species in which cultured cells are used for transformation, non-chimeric plants can be obtained when regeneration occurs from mutated cells. Since plantlets are regenerated from both mutated and non-mutated cells in a random manner, any increment in the proportion of mutated cells in Cas9- and guide RNA (gRNA)-expressing cells will help increase the number of plants containing heritable mutations. In this study, we examined factors affecting mutation frequency in rice calli. Following sequential transformation of rice calli with Cas9- and gRNA- expression constructs, the mutation frequency in independent Cas9 transgenic lines was analyzed. A positive correlation between Cas9 expression level and mutation frequency was found. This positive relationship was observed regardless of whether the transgene or an endogenous gene was used as the target for CRISPR/Cas9-mediated mutagenesis. Furthermore, we found that extending the culture period increased the proportion of mutated cells as well as the variety of mutations obtained. Because mutated and non-mutated cells might proliferate equally, these results suggest that a prolonged tissue culture period increases the chance of inducing de novo mutations in non-mutated cells. This fundamental knowledge will help improve systems for obtaining non-chimeric regenerated plants in many plant species. PMID- 26134857 TI - UV/Vis Spectroscopy Studies of the Photoisomerization Kinetics in Self-Assembled Azobenzene-Containing Adlayers. AB - Direct comparative studies of the photoisomerization of azobenzene derivatives in self-assembled adlayers on Au and as free molecules in dichloromethane solution were performed using UV/vis spectroscopy. For all studied systems a highly reversible trans-cis isomerization in the adlayer is observed. Quantitative studies of the absorbance changes and photoisomerization kinetics reveal that in azobenzenes mounted as freestanding vertical groups on the surface via triazatriangulene-based molecular platforms photoswitching is nearly uninhibited by the local environment in the adlayer. The blue-shift of the pi-pi* transition in adlayers of these molecules is in good agreement with theoretical studies of the effect of excitonic coupling between the molecules. In contrast, in azobenzene-containing thiol self-assembled monolayers the fraction of photoswitching molecules and the photoisomerization kinetics are significantly reduced compared to free molecules in solution. PMID- 26134858 TI - Identification of a member of the catalase multigene family on wheat chromosome 7A associated with flour b* colour and biological significance of allelic variation. AB - Carotenoids (especially lutein) are known to be the pigment source for flour b* colour in bread wheat. Flour b* colour variation is controlled by a quantitative trait locus (QTL) on wheat chromosome 7AL and one gene from the carotenoid pathway, phytoene synthase, was functionally associated with the QTL on 7AL in some, but not all, wheat genotypes. A SNP marker within a sequence similar to catalase (Cat3-A1snp) derived from full-length (FL) cDNA (AK332460), however, was consistently associated with the QTL on 7AL and implicated in regulating hydrogen peroxide (H2O2) to control carotenoid accumulation affecting flour b* colour. The number of catalase genes on chromosome 7AL was investigated in this study to identify which gene may be implicated in flour b* variation and two were identified through interrogation of the draft wheat genome survey sequence consisting of five exons and a further two members having eight exons identified through comparative analysis with the single catalase gene on rice chromosome 6, PCR amplification and sequencing. It was evident that the catalase genes on chromosome 7A had duplicated and diverged during evolution relative to its counterpart on rice chromosome 6. The detection of transcripts in seeds, the co location with Cat3-A1snp marker and maximised alignment of FL-cDNA (AK332460) with cognate genomic sequence indicated that TaCat3-A1 was the member of the catalase gene family associated with flour b* colour variation. Re-sequencing identified three alleles from three wheat varieties, TaCat3-A1a, TaCat3-A1b and TaCat3-A1c, and their predicted protein identified differences in peroxisomal targeting signal tri-peptide domain in the carboxyl terminal end providing new insights into their potential role in regulating cellular H2O2 that contribute to flour b* colour variation. PMID- 26134859 TI - What has become more acceptable? Continuity and changes in older adults' attitudes toward end-of-life care in Japan. PMID- 26134860 TI - Treatment of idiopathic thrombocytopenic purpura in the elderly: A challenge for geriatricians. PMID- 26134861 TI - Effect of Laughing Qigong on an elderly population. PMID- 26134862 TI - X-Linked Retinitis Pigmentosa 2 Is a Novel Maternal-Effect Gene Required for Left Right Asymmetry in Zebrafish. AB - Retinitis pigmentosa 2 (RP2) gene is responsible for up to 20% of X-linked retinitis pigmentosa, a severe heterogeneous genetic disorder resulting in progressive retinal degeneration in humans. In vertebrates, several bodies of evidence have clearly established the role of Rp2 protein in cilia genesis and/or function. Unexpectedly, some observations in zebrafish have suggested the oocyte predominant expression of the rp2 gene, a typical feature of maternal-effect genes. In the present study, we investigate the maternal inheritance of rp2 gene products in zebrafish eggs in order to address whether rp2 could be a novel maternal-effect gene required for normal development. Although both rp2 mRNA and corresponding protein are expressed during oogenesis, rp2 mRNA is maternally inherited, in contrast to Rp2 protein. A knockdown of the protein transcribed from both rp2 maternal and zygotic mRNA results in delayed epiboly and severe developmental defects, including eye malformations, that were not observed when only the protein from zygotic origin was knocked down. Moreover, the knockdown of maternal and zygotic Rp2 revealed a high incidence of left-right asymmetry establishment defects compared to only zygotic knockdown. Here we show that rp2 is a novel maternal-effect gene exclusively expressed in oocytes within the zebrafish ovary and demonstrate that maternal rp2 mRNA is essential for successful embryonic development and thus contributes to egg developmental competence. Our observations also reveal that Rp2 protein translated from maternal mRNA is important to allow normal heart loop formation, thus providing evidence of a direct maternal contribution to left-right asymmetry establishment. PMID- 26134864 TI - Novel technique for visualizing primordial germ cells in sturgeons (Acipenser ruthenus, A. gueldenstaedtii, A. baerii, and Huso huso). AB - Primordial germ cells (PGCs) are the origin of all germ cells in developing embryos. In the sturgeon embryo, PGCs develop from the vegetal hemisphere, which mainly acts as an extraembryonic source of nutrition. Current methods for studying sturgeon PGCs require either killing the fish or using costly and time consuming histological procedures. Here, we demonstrate that visualization of sterlet (Acipenser ruthenus>) PGCs in vivo is feasible by simply labeling the vegetal hemisphere with fluorescein isothiocyanate (FITC)-dextran. We injected FITC-dextrans, with molecular weights varying between 10 000 and 2 000 000, into the vegetal pole of 1- to 4-cell stage embryos. At the neurula to tail-bud developmental stages, FITC-positive PGC-like cells appeared ventrally around the developing tail bud in the experimental group that received a high-molecular weight FITC-dextran. The highest average number of FITC-positive PGC-like cells was observed in embryos injected with FITC-dextran having a molecular weight of 500 000 (FD-500). The pattern of migration of the labeled cells was identical to that of PGCs, clearly indicating that the FITC-positive PGC-like cells were PGCs. Labeled vegetal cells, except for the PGCs, were digested and excreted before the embryos starting feeding. FITC-labeled PGCs were observed in the developing gonads of fish for at least 3 mo after injection. We also found that FD-500 could be used to visualize PGCs in other sturgeon species. To the best of our knowledge, this report is the first to demonstrate in any animal species that PGCs can be visualized in vivo for a long period by the injection of a simple reagent. PMID- 26134865 TI - LH-Independent Testosterone Secretion Is Mediated by the Interaction Between GNRH2 and Its Receptor Within Porcine Testes. AB - Unlike classic gonadotropin-releasing hormone 1 (GNRH1), the second mammalian isoform (GNRH2) is an ineffective stimulant of gonadotropin release. Species that produce GNRH2 may not maintain a functional GNRH2 receptor (GNRHR2) due to coding errors. A full-length GNRHR2 gene has been identified in swine, but its role in reproduction requires further elucidation. Our objective was to examine the role of GNRH2 and GNRHR2 in testicular function of boars. We discovered that GNRH2 levels were higher in the testis than in the anterior pituitary gland or hypothalamus, corresponding to greater GNRHR2 abundance in the testis versus the anterior pituitary gland. Moreover, GNRH2 immunostaining was most prevalent within seminiferous tubules, whereas GNRHR2 was detected in high abundance on Leydig cells. GNRH2 pretreatment of testis explant cultures elicited testosterone secretion similar to that of human chorionic gonadotropin stimulation. Treatment of mature boars with GNRH2 elevated testosterone levels similar to those of GNRH1 treated males, despite minimal GNRH2-induced release of luteinizing hormone (LH). When pretreated with a GNRHR1 antagonist (SB-75), subsequent GNRH2 treatment stimulated low levels of testosterone secretion despite a pattern of LH release similar to that in the previous trial, suggesting that SB-75 inhibited testicular GNRHR2s. Given that pigs lack testicular GNRHR1, these data may indicate that GNRH2 and its receptor are involved in autocrine or paracrine regulation of testosterone secretion. Notably, our data are the first to suggest a biological function of a novel GNRH2-GNRHR2 system in the testes of swine. PMID- 26134866 TI - The Critical Hormone-Sensitive Window for the Development of Delayed Effects Extends to 10 Days after Birth in Female Rats Postnatally Exposed to 17alpha Ethynylestradiol. AB - Neonatal exposure to estrogens is known to cause delayed effects, a late occurring adverse effect on adult female reproductive functions, such as early onset of age-matched abnormal estrous cycling. However, the critical period in which neonates are sensitive to delayed effects inducible by exogenous estrogen exposure has not been clearly identified. To clarify this window, we examined the intensity and timing of delayed effects using rats exposed to ethynylestradiol (EE) at various postnatal ages. After subcutaneous administration of a single dose of EE (20 MUg/kg, which induces delayed effects) on Postnatal Day (PND) 0, 5, 10, or 14 in Wistar rats, hypothalamic and hormonal alterations in young adults and long-term estrous cycling status were investigated as indicators of delayed effects. In young adults, peak luteinizing hormone concentrations at the time of the luteinizing hormone surge showed a decreasing trend, and KiSS1 mRNA expression of the anterior hypothalamus and number of KiSS1-positive cells in the anteroventral periventricular nucleus were significantly decreased in the PND 0, 5, and 10 groups. The reduction in KiSS1 mRNA and KiSS1-postive cells was inversely correlated with age at time of exposure. These groups also exhibited early onset of abnormal estrous cycling, starting from 17 wk of age in the PND0 group and 19 wk of age in the PND5 and 10 groups. These indicators were not apparent in the PND14 group. Our results suggest that PND0-PND10 is the critical window of susceptibility for delayed effects, and PND14 is presumed to be the provisional endpoint of the window. PMID- 26134867 TI - The Role of Endometrial Selectins and Their Ligands on Bovine Conceptus Attachment to the Uterine Epithelium During Peri-Implantation Period. AB - A successful pregnancy depends on the blastocyst's implantation to the maternal endometrium; however, the initial interaction between blastocyst and uterine epithelium has not been well characterized. The objectives of this study were to determine if selectins and their ligands were expressed in the bovine conceptus and/or uterus during the periattachment period and to study whether selectins were associated with conceptus attachment to the uterine epithelium. Through the RNA-sequence analysis of bovine conceptuses on Days 17, 20, and 22 (Day 0 = day of estrus), only the SELL ligand, podocalyxin (PODXL), and P-selectin (SELP) ligand, SELPLG, were found. Quantitative PCR analysis confirmed the presence of PODXL and SELPLG in these conceptuses and revealed that SELL, mRNA and protein, detected in the uterine epithelium but not in conceptuses increased during the periattachment period. In the cultured endometrial epithelial cells (EECs), SELL transcript was up-regulated when uterine flushings from Day 20 pregnant animals were placed onto these cells. SELL was also up-regulated when cultured EECs were treated with progesterone, EGF, or bFGF, but not with IFNT. In the coculture system with EECs and bovine trophoblast CT-1 cells, SELL expression in EECs was effectively reduced by its small interfering RNA; however, IFNT, a marker for CT 1 cell attachment to EECs, was not reduced, nor was a transcription factor of IFNT, CDX2. These observations suggest that the conceptus could attach to the uterine epithelium through the use of endometrial SELL and embryonic selectin ligands, possibly initiating the conceptus attachment process in the bovine species. PMID- 26134868 TI - Coordinated Action of Aquaporins Regulates Sperm Motility in a Marine Teleost. AB - In marine teleosts, such as the gilthead seabream, several aquaporin paralogs are known to be expressed during the hyperosmotic induction of spermatozoon motility in seawater. Here, we used immunological inhibition of channel function to investigate the physiological roles of Aqp1aa, Aqp1ab, and Aqp7 during seabream sperm activation. Double immunofluorescence microscopy of SW-activated sperm showed that Aqp1aa and Aqp7 were respectively distributed along the flagellum and the head, whereas Aqp1ab accumulated in the head and in discrete areas toward the anterior tail. Inhibition of Aqp1aa reduced the rise of intracellular Ca(2+), which is independent of external Ca(2+) and normally occurs upon activation, and strongly inhibited sperm motility. Impaired Aqp1aa function also prevented the intracellular trafficking of Aqp8b to the mitochondrion, where it acts as a peroxiporin allowing H2O2 efflux and ATP production during activation. However, restoring the Ca(2+) levels with a Ca(2+) ionophore in spermatozoa with immunosuppressed Aqp1aa function fully rescued mitochondrial Aqp8b accumulation and sperm motility. In contrast, exposure of sperm to Aqp1ab and Aqp7 antibodies did not affect motility during the initial phase of activation, but latently compromised the trajectory and the pattern of movement. These data reveal the coordinated action of spatially segregated aquaporins during sperm motility activation in a marine teleost, where flagellar-localized Aqp1aa plays a dual Ca(2+)-dependent role controlling the initiation of sperm motility and the activation of mitochondrial detoxification mechanisms, while Aqp1ab and Aqp7 in the head and anterior tail direct the motion pattern. PMID- 26134870 TI - The Incidence of DNA Double-Strand Breaks Is Higher in Late-Cleaving and Less Developmentally Competent Porcine Embryos. AB - Studies in different species, including human, mice, bovine, and swine, demonstrated that early-cleaving embryos have higher capacity to develop to the blastocyst stage and produce better quality embryos with superior capacity to establish pregnancy than late-cleaving embryos. It has also been shown that experimentally induced DNA damage delays embryo cleavage kinetics and reduces blastocyst formation. To gain additional insights into the effects of genome damage on embryo cleavage kinetics and development, the present study compared the occurrence of DNA double-strand breaks (DSBs) with the expression profile of genes involved in DNA repair and cell cycle control between early- and late cleaving embryos. Porcine oocytes matured in vitro were activated, and then early cleaving (before 24 h) and late-cleaving (between 24 and 48 h) embryos were identified and cultured separately. Developing embryos, on Days 3, 5, and 7, were used to evaluate the total cell number and presence of DSBs (by counting the number of immunofluorescent foci for phosphorylated histone H2A.x [H2AX139ph] and RAD51 proteins) and to quantify transcripts of genes involved in DNA repair and cell cycle control by quantitative RT-PCR. Early-cleaving embryos had fewer DSBs, lower transcript levels for genes encoding DNA repair and cell cycle checkpoint proteins, and more cells than late-cleaving embryos. Interestingly, at the blastocyst stage, embryos that developed from early- and late-cleaving groups had similar number of DSBs as well as transcript levels of genes induced by DNA damage. This indicates that only embryos with less DNA damage and/or superior capacity for DNA repair are able to progress to the blastocyst stage. Collectively, findings in this study revealed a negative correlation between the occurrence of DSBs and embryo cleavage kinetics and embryo developmental capacity to the blastocyst stage. PMID- 26134869 TI - Embryonic Poly(A)-Binding Protein Is Required During Early Stages of Mouse Oocyte Development for Chromatin Organization, Transcriptional Silencing, and Meiotic Competence. AB - During oocyte maturation, fertilization, and early embryo development until zygotic genome activation (ZGA), transcription is suppressed, and gene expression is dependent upon the timely activation of stored mRNAs. Embryonic poly(A) binding protein (EPAB) is the predominant poly(A)-binding protein in Xenopus, mouse, and human oocytes and early embryos and is important for regulating translational activation of maternally stored mRNAs. EPAB is critical for early development because Epab(-/-) female mice do not produce mature eggs and are infertile. In this study, we further characterize morphological and molecular aspects of Epab(-/-) oocytes. We demonstrated that Epab(-/-) oocytes are smaller in size, contain peripheral germinal vesicles, and are loosely associated with cumulus cells. The chromatin reorganization of the surrounded nucleolus (SN) configuration and transcriptional silencing that normally occurs during oocyte growth does not occur in Epab(-/-) oocytes. Interestingly, microinjection of Epab mRNA into Epab(-/-) preantral follicle-enclosed oocytes rescues reorganization of chromatin and oocyte maturation to metaphase II. Overall, these results demonstrate an important role for EPAB during oocyte growth and the acquisition of meiotic competence. PMID- 26134872 TI - IN MEMORIAM Stanley R. Glasser, Ph.D. 1926-2015. PMID- 26134871 TI - Mobilization of Dormant Cnot7 mRNA Promotes Deadenylation of Maternal Transcripts During Mouse Oocyte Maturation. AB - Maternal mRNAs in oocytes are remarkably stable. In mouse, oocyte maturation triggers a transition from mRNA stability to instability. This transition is a critical event in the oocyte-to-embryo transition in which a differentiated oocyte loses its identity as it is transformed into totipotent blastomeres. We previously demonstrated that phosphorylation of MSY2, an RNA-binding protein, and mobilization of mRNAs encoding the DCP1A-DCP2 decapping complex contribute to maternal mRNA destruction during meiotic maturation. We report here that Cnot7, Cnot6l, and Pan2, key components of deadenylation machinery, are also dormant maternal mRNAs that are recruited during oocyte maturation. Inhibiting the maturation-associated increase in CNOT7 (or CNOT6L) using a small interference RNA approach inhibits mRNA deadenylation, whereas inhibiting the increase in PAN2 has little effect. Reciprocally, expressing CNOT7 (or CNOT6L) in oocytes prevented from resuming meiosis initiates deadenylation of mRNAs. These effects on deadenylation are also observed when the total amount of poly (A) is quantified. Last, inhibiting the increase in CNOT7 protein results in an ~70% decrease in transcription in 2-cell embryos. PMID- 26134873 TI - RITA enhances irradiation-induced apoptosis in p53-defective cervical cancer cells via upregulation of IRE1alpha/XBP1 signaling. AB - Radiation therapy is the most widely used treatment for patients with cervical cancer. Recent studies have shown that endoplasmic reticulum (ER) stress induces apoptosis and sensitizes tumor cells to radiotherapy, which reportedly induces ER stress in cells. Classical key tumor suppressor p53 is involved in the response to a variety of cellular stresses, including those incurred by ionizing irradiation. A recent study demonstrated that small-molecule RITA (reactivation of p53 and induction of tumor cell apoptosis) increased the radiosensitivity of tumor cells expressing mutant p53 (mtp53). In the present study, we explored the effects and the underlying mechanisms of RITA in regards to the radiosensitivity and ER stress in mtp53-expressing human cervix cancer cells. Treatment with 1 uM of RITA for 24 h before irradiation markedly decreased survival and increased apoptosis in C-33A and HT-3 cells; the effects were not significantly altered by knockdown of p53. In the irradiated C-33A and HT-3 cells, RITA significantly increased the expression of IRE1alpha, the spliced XBP1 mRNA level, as well as apoptosis; the effects were abolished by knockdown of IRE1alpha. Transcriptional pulse-chase assays revealed that RITA significantly increased the stability of IRE1alpha mRNA in the irradiated C-33A and HT-3 cells. In contrast, the same RITA treatment did not show any significant effect on sham-irradiated cells. In conclusion, the present study provides initial evidence that RITA upregulates the expression level of IRE1alpha by increasing the stability of IRE1alpha mRNA in irradiated mtp53-expressing cervical cancer cells; the effect leads to enhanced IRE1alpha/XBP1 ER stress signaling and increased apoptosis in the cells. The present study offers novel insight into the pharmacological potential of RITA in the radiotherapy for cervical cancer. PMID- 26134874 TI - Secondary education and HIV infection in Botswana. PMID- 26134876 TI - The influence of growth patterns on sexual size monomorphism in lemurs. AB - The lack of sexual size dimorphism among lemurs is puzzling given the high degree of polygyny in this clade. It has been proposed that the unique ecological conditions of Madagascar favour rapid completion of growth, limiting the opportunities for bimaturism and sexual size dimorphism in lemurs. Using recently compiled large data sets on many species across the lemur clade, I examined the prevalence of sexual size monomorphism of body mass among lemurs and tested the hypothesis that limited growth durations constrain sexual size dimorphism. I used segmented regression analyses to accurately model growth in each species. The majority of species analysed exhibited a period of rapid growth followed by a distinct period of slow growth prior to attainment of adult body mass. Whereas the first period of growth was constrained by the need to attain the majority of adult body mass prior to the onset of the infant's first dry season, the subsequent period of slow growth was unconstrained and sufficiently long to promote sexual bimaturism. Sex differences in the duration and rate of growth during this second growth phase appeared to account for the sexual size dimorphism exhibited by three lemur species. Therefore, constraints on growth processes do not limit sexual size dimorphism in lemurs, and other explanations for the prevalence of sexual size monomorphism in this clade should be examined. The importance of considering ontogeny in future investigations of sexual size monomorphism in lemurs is highlighted. PMID- 26134875 TI - Length of secondary schooling and risk of HIV infection in Botswana: evidence from a natural experiment. AB - BACKGROUND: An estimated 2.1 million individuals are newly infected with HIV every year. Cross-sectional and longitudinal studies have reported conflicting evidence for the association between education and HIV risk, and no randomised trial has identified a causal effect for education on HIV incidence. We aimed to use a policy reform in secondary schooling in Botswana to identify the causal effect of length of schooling on new HIV infection. METHODS: Data for HIV biomarkers and demographics were obtained from the nationally representative household 2004 and 2008 Botswana AIDS Impact Surveys (N=7018). In 1996, Botswana reformed the grade structure of secondary school, expanding access to grade ten and increasing educational attainment for affected cohorts. Using exposure to the policy reform as an instrumental variable, we used two-stage least squares to estimate the causal effect of years of schooling on the cumulative probability that an individual contracted HIV up to their age at the time of the survey. We also assessed the cost-effectiveness of secondary schooling as an HIV prevention intervention in comparison to other established interventions. FINDINGS: Each additional year of secondary schooling caused by the policy change led to an absolute reduction in the cumulative risk of HIV infection of 8.1 percentage points (p=0.008), relative to a baseline prevalence of 25.5% in the pre-reform 1980 birth cohort. Effects were particularly large in women (11.6 percentage points, p=0.046). Results were robust to a wide array of sensitivity analyses. Secondary school was cost effective as an HIV prevention intervention by standard metrics (cost per HIV infection averted was US$27 753). INTERPRETATION: Additional years of secondary schooling had a large protective effect against HIV risk in Botswana, particularly for women. Increasing progression through secondary school could be a cost-effective HIV prevention measure in HIV-endemic settings, in addition to yielding other societal benefits. FUNDING: Takemi Program in International Health at the Harvard T.H.Chan School of Public Health, Belgian American Educational Foundation, Fernand Lazard Foundation, Boston University, National Institutes of Health. PMID- 26134877 TI - 807C/T polymorphism of platelet glycoprotein Ia gene is associated with cerebral hemorrhage in a Chinese population. AB - Platelet glycoprotein (GP) mediated the role of platelet in coagulation. Platelet GP Ia 807C/T is the only GP polymorphism associated with the expression levels of GP Ia/IIa (the platelet collagen receptor). Recently, the GP Ia 807C/T polymorphism has been reported to have no association with cerebral hemorrhage (CH) in two studies pertained to Caucasian populations. The purpose of this study is to evaluate the association between platelet GP Ia 807C/T polymorphism and CH in a Han Chinese population. We performed genotype analysis for platelet GP Ia 807C/T polymorphism in a case-control study involving 195 patients with CH and 116 age- and sex-matched controls. In contrast to previous reports, we found that the frequencies of GP Ia 807C/T T allele, CT and TT genotype were much higher in CH patients than in controls (33.9% vs. 22.8%, p = 0.004; 45.5% and 11.1% vs. 40.4% and 2.6%, p = 0.022). Logistic regression analysis revealed that the presence of GP Ia 807C/T C allele and CC genotype were both associated with a decreased risk of CH compared with T allele, CT and TT genotypes, respectively (adjusted odds ratio [OR] = 0.565, 95% CI: 0.384-0.887, p = 0.005; adjusted OR = 0.172, 95% CI: 0.043-0.639, p = 0.009; adjusted OR = 0.254, 95% CI: 0.085-0.961, p = 0.041, respectively). These findings indicated that platelet GP Ia 807C/T polymorphism could be a protective factor of CH in the Chinese population. PMID- 26134878 TI - MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease. AB - OBJECTIVE: To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). METHODS: Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. RESULTS: One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. CONCLUSIONS: This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD. PMID- 26134879 TI - Red-fleshed Apples: Old Autochthonous Fruits as a Novel Source of Anthocyanin Antioxidants. AB - In order to promote breeding programs and a full reintroduction into production of two local red-fleshed apple varieties grown in Bekran and Bastam (Iran), the evaluation of their antioxidant properties was of interest. LC-MS(n) based metabolic fingerprinting analyses were applied to investigate the anthocyanin content of both peel and flesh components of the fruits. Cyanidin-3-O-hexoside isomers were present in both 'Bekran' and 'Bastam' apples, whereas 'Bekran' apple was a valuable source of anthocyanin rutinose derivatives. Employing DPPH(*), ABTS(*+), and ORAC methods, the antiradical efficacy was evaluated. The ability of the investigated fruit components to scavenge OH(*), and O(2) (*-) reactive species was also assessed. ID(50) values highlighted the massive antioxidant response of 'Bekran' peel component, able to counteract by 50 % OH(*), and O(2) (*-) at 130.3 and 91.6 MUg/mL, respectively. The cytoprotective screening towards HeLa, HepG2, A549, SH-5YSY, and SK-N-BE(2)-C cell lines evidenced that the investigated Iranian red-fleshed apple fruits were able to exert a significant antioxidant response in hydrogen peroxide oxidized cell systems. Data collected suggested that the revaluation of 'Bekran' and 'Bastam' apple cultivars could represent a precious source of antioxidant compounds whose dietary intake could improve the human well-being reducing risks of free radical related chronic and degenerative diseases. PMID- 26134880 TI - Computing the various pathways of penicillin synthesis and their molar yields. AB - More than 80 years after its discovery, penicillin is still a widely used and commercially highly important antibiotic. Here, we analyse the metabolic network of penicillin synthesis in Penicillium chrysogenum based on the concept of elementary flux modes. In particular, we consider the synthesis of the invariant molecular core of the various subtypes of penicillin and the two major ways of incorporating sulfur: transsulfuration and direct sulfhydrylation. 66 elementary modes producing this invariant core are obtained. These show four different yields with respect to glucose, notably 1/2, 2/5, 1/3, and 2/7, with the highest yield of 1/2 occurring only when direct sulfhydrylation is used and alpha aminoadipate is completely recycled. In the case of no recycling of this intermediate, we find the maximum yield to be 2/7. We compare these values with earlier literature values. Our analysis provides a systematic overview of the redundancy in penicillin synthesis and a detailed insight into the corresponding routes. Moreover, we derive suggestions for potential knockouts that could increase the average yield. PMID- 26134882 TI - Cytomegalovirus Peritonitis Without Gut Perforation But With Concomitant Colitis After a Liver Allograft Transplant. AB - We present a 24-year-old man who developed primary cytomegalovirus peritonitis without gut perforation, but with concomitant colitis 6 weeks after liver transplant from a deceased donor for end-stage liver disease because of primary sclerosing cholangitis. The patient was treated only medically, with no need for surgery, and is well at 12 months. This case represents the need for suspicious for cytomegalovirus peritonitis in the appropriate setting in post liver transplant even in the absence of perforation. PMID- 26134881 TI - The effect of antidepressant treatment on HIV and depression outcomes: results from a randomized trial. AB - BACKGROUND: Depression is a major barrier to HIV treatment outcomes. OBJECTIVE: To test whether antidepressant management decision support integrated into HIV care improves antiretroviral adherence and depression morbidity. DESIGN: Pseudo cluster randomized trial. SETTING: Four US infectious diseases clinics. PARTICIPANTS: HIV-infected adults with major depressive disorder. INTERVENTION: Measurement-based care (MBC) - depression care managers used systematic metrics to give HIV primary-care clinicians standardized antidepressant treatment recommendations. MEASUREMENTS: Primary - antiretroviral medication adherence (monthly unannounced telephone-based pill counts for 12 months). Primary time point - 6 months. Secondary - depressive severity, depression remission, depression-free days, measured quarterly for 12 months. RESULTS: From 2010 to 2013, 149 participants were randomized to intervention and 155 to usual care. Participants were mostly men, Black, non-Hispanic, unemployed, and virally suppressed with high baseline self-reported antiretroviral adherence and depressive severity. Over follow-up, no differences between arms in antiretroviral adherence or other HIV outcomes were apparent. At 6 months, depressive severity was lower among intervention participants than usual care [mean difference -3.7, 95% confidence interval (CI) -5.6, -1.7], probability of depression remission was higher [risk difference 13%, 95% CI 1%, 25%), and suicidal ideation was lower (risk difference -18%, 95% CI -30%, -6%). By 12 months, the arms had comparable mental health outcomes. Intervention arm participants experienced an average of 29 (95% CI: 1-57) more depression-free days over 12 months. CONCLUSION: In the largest trial of its kind among HIV infected adults, MBC did not improve HIV outcomes, possibly because of high baseline adherence, but achieved clinically significant depression improvements and increased depression-free days. MBC may be an effective, resource-efficient approach to reducing depression morbidity among HIV patients. PMID- 26134883 TI - COCATS 4 Task Force 6: Training in Nuclear Cardiology : Endorsed by the American Society of Nuclear Cardiology. PMID- 26134884 TI - COCATS 4 Task Force 7: Training in Cardiovascular Computed Tomographic Imaging : Endorsed by the American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Atherosclerosis Imaging and Prevention, and the Society of Cardiovascular Computed Tomography. PMID- 26134885 TI - Comparative analysis of cadmium-zincum-telluride cameras dedicated to myocardial perfusion SPECT: A phantom study. AB - BACKGROUND: This investigation used image data generated by an anthropomorphic phantom with a cardiac insert for a comparison between two solid state cameras: D SPECT and D530c. METHODS: For each camera, two sets (with and without a simulated transmural defect (TD)) of scans were acquired starting from the in vivo standard count statistics in the left ventricle (LV). Other two acquisitions corresponding to 150% and 50% of the reference count statistics were acquired. Five performance indices related to spatial resolution, contrast, and contrast-to-noise ratio (CNR) were analyzed. RESULTS: D-SPECT showed a lower LV wall thickness and an inferior sharpness than D530c. No significant differences were found in terms of contrast between LV wall and the inner cavity, TD contrast or CNR. No significant differences were observed in CNR when moving from the reference level of count statistics down to 50% or up to 150% of the counts acquired on the LV. CONCLUSIONS: Our results show that D-SPECT and D530c have different performances. The lack of differences in the image performance indices along the range of count statistics explored, indicates that there is the possibility for a further reduction in the injected activity and/or the acquisition time, for both systems. PMID- 26134886 TI - Time to move to PET-MR for cardiovascular imaging. PMID- 26134888 TI - Crystal Structure and Catalytic Behavior in Olefin Epoxidation of a One Dimensional Tungsten Oxide/Bipyridine Hybrid. AB - The tungsten oxide/2,2'-bipyridine hybrid material [WO3(2,2'-bpy)].nH2O (n = 1-2) (1) has been prepared in near quantitative yield by the reaction of H2WO4, 2,2' bpy, and H2O in the mole ratio of ca. 1:2:700 at 160 degrees C for 98 h in a rotating Teflon-lined digestion bomb. The solid-state structure of 1 was solved and refined through Rietveld analysis of high-resolution synchrotron X-ray diffraction data collected for the microcrystalline powder. The material, crystallizing in the orthorhombic space group Iba2, is composed of a one dimensional organic-inorganic hybrid polymer, infinity(1)[WO3(2,2'-bpy)], topologically identical to that found in the previously reported anhydrous phases [MO3(2,2'-bpy)] (M = Mo, W). While in the latter the N,N'-chelated 2,2'-bpy ligands of adjacent corner-shared {MO4N2} octahedra are positioned on the same side of the 1D chain, in 1 the 2,2'-bpy ligands alternate above and below the chain. The catalytic behavior of compound 1 for the epoxidation of cis cyclooctene was compared with that for several other tungsten- or molybdenum based (pre)catalysts, including the hybrid polymer [MoO3(2,2'-bpy)]. While the latter exhibits superior performance when tert-butyl hydroperoxide (TBHP) is used as the oxidant, compound 1 is superior when aqueous hydrogen peroxide is used, allowing near-quantitative conversion of the olefin to the epoxide. With H2O2, compounds 1 and [MoO3(2,2'-bpy)] act as sources of soluble active species, namely, the oxodiperoxo complex [MO(O2)2(2,2'-bpy)], which is formed in situ. Compounds 1 and [WO(O2)2(2,2'-bpy)] (2) were further tested in the epoxidation of cyclododecene, trans-2-octene, 1-octene, (R)-limonene, and styrene. The structure of 2 was determined by single-crystal X-ray diffraction and found to be isotypical with the molybdenum analogue. PMID- 26134889 TI - Selective photosensitization through an AND logic response: optimization of the pH and glutathione response of activatable photosensitizers. AB - A series of pH and GSH responsive photosensitizers were designed and synthesized. pKa values were optimized by adjusting the inductive contribution of substituents to reach a pH range (6.0-7.4) relevant to the tumour microenvironment. pH Activatable behaviour and redox mediated release of the quencher from the PS by GSH allow the construction of an AND logic operator for selective photodynamic action in aqueous solutions. PMID- 26134890 TI - Temperature dependent structural variations of OH(-)(H2O)n, n = 4-7: effects on vibrational and photoelectron spectra. AB - In this work, we identified a large number of structurally distinct isomers of midsized deprotonated water clusters, OH(-)(H2O)n=4-7, using first-principles methods. The temperature dependence of the structural variation in the solvation shell of OH(-) for these clusters was examined under the harmonic superposition approximation. We simulated the vibrational and photoelectron spectra based on these thermodynamic calculations. We found that the isomers with 3-coordinated hydroxide dominate the population in these midsized clusters. Furthermore, an increase in temperature causes a topological change from compact isomers with many intermolecular hydrogen bonds to open isomers with fewer but more directional intermolecular hydrogen bonds. We showed that this evolution in structure can be observed through the change in the vibrational spectra at 3200 3400 cm(-1). In addition, the increase in directional hydrogen bonded isomers, which have outer hydration shell with OH bonds pointing to the hydroxide, causes the vertical detachment energy to increase at higher temperatures. Lastly, we also performed studies to understand the variation in the aforementioned spectral quantities with the variation in the coordination number of the hydroxide. PMID- 26134892 TI - Baroreceptor activity impacts upon controlled but not automatic distractor processing. AB - Changes within the cardiovascular system have been shown to alter sensorimotor and memory performance, pain perception as well as cortical arousal. This influence is assumed to be mediated by afferent feedback of baroreceptors that when stimulated exert inhibitory effects on cortical structures. Mainly responsible for short-term regulation of blood pressure, afferents of the baroreceptors are widely connected to subcortical and cortical structures like the insular cortex. A putative impact on cognitive control processes remains an open question, however. Using a sequential distractor priming task, the present study investigated whether inhibitory influences of baroreceptor activation apply to selective information processing in the presence of irrelevant information. In particular, we assessed distractor-response binding and Negative Priming as indices of automatic and controlled distractor processing, respectively. Baroreceptor activation was experimentally manipulated by the systematic variation of body position. The results showed that only Negative Priming but not distractor-response binding was modulated by body position suggesting that controlled but not automatic processing of distractors is affected by baroreceptor activity. PMID- 26134893 TI - A genetic approach to improving the lives of racing Thoroughbreds. PMID- 26134891 TI - Dyspnea-related cues engage the prefrontal cortex: evidence from functional brain imaging in COPD. AB - BACKGROUND: Dyspnea is the major source of disability in COPD. In COPD, environmental cues (eg, the prospect of having to climb stairs) become associated with dyspnea and may trigger dyspnea even before physical activity commences. We hypothesized that brain activation relating to such cues would be different between patients with COPD and healthy control subjects, reflecting greater engagement of emotional mechanisms in patients. METHODS: Using functional MRI (FMRI), we investigated brain responses to dyspnea-related word cues in 41 patients with COPD and 40 healthy age-matched control subjects. We combined these findings with scores on self-report questionnaires, thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enabled identification of brain networks responsible for pain processing despite absence of a physical challenge. RESULTS: Patients with COPD demonstrated activation in the medial prefrontal cortex and anterior cingulate cortex, which correlated with the visual analog scale (VAS) response to word cues. This activity independently correlated with patient responses on questionnaires of depression, fatigue, and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex, and precuneus correlated with the VAS dyspnea scale but not with the questionnaires. CONCLUSIONS: The findings suggest that engagement of the emotional circuitry of the brain is important for interpretation of dyspnea-related cues in COPD and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and the findings suggest that such mechanisms may be relevant in COPD. PMID- 26134894 TI - Stimulation of angiogenesis by cilostazol accelerates fracture healing in mice. AB - Cilostazol, a selective phosphodiesterase-3 inhibitor, is known to control cyclic adenosine monophosphate (c-AMP) and to stimulate angiogenesis through upregulation of pro-angiogenic factors. There is no information, however, whether cilostazol affects fracture healing. We, therefore, studied the effect of cilostazol on callus formation and biomechanics during fracture repair. Bone healing was analyzed in a murine femur fracture stabilized with an intramedullary screw. Radiological, biomechanical, histomorphometric, histochemical, and protein biochemical analyses were performed at 2 and 5 weeks after fracture. Twenty-five mice received 30 mg/kg body weight cilostazol p.o. daily. Controls (n=24) received equivalent amounts of vehicle. In cilostazol-treated animals radiological analysis at 2 weeks showed an improved healing with an accelerated osseous bridging compared to controls. This was associated with a significantly higher amount of bony tissue and a smaller amount of cartilage tissue within the callus. Western blot analysis showed a higher expression of cysteine-rich protein 61 (CYR61), bone morphogenetic protein (BMP)-4, and receptor activator of NF kappaB ligand (RANKL). At 5 weeks, improved fracture healing after cilostazol treatment was indicated by biomechanical analyses, demonstrating a significant higher bending stiffness compared to controls. Thus, cilostazol improves fracture healing by accelerating both bone formation and callus remodeling. PMID- 26134895 TI - Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation. AB - Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software((r))) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development. PMID- 26134896 TI - The beta-hairpin of 40S exit channel protein Rps5/uS7 promotes efficient and accurate translation initiation in vivo. AB - The eukaryotic 43S pre-initiation complex bearing tRNAi(Met) scans the mRNA leader for an AUG start codon in favorable context. Structural analyses revealed that the beta-hairpin of 40S protein Rps5/uS7 protrudes into the 40S mRNA exit channel, contacting the eIF2?GTP?Met-tRNAi ternary complex (TC) and mRNA context nucleotides; but its importance in AUG selection was unknown. We identified substitutions in beta-strand-1 and C-terminal residues of yeast Rps5 that reduced bulk initiation, conferred 'leaky-scanning' of AUGs; and lowered initiation fidelity by exacerbating the effect of poor context of the eIF1 AUG codon to reduce eIF1 abundance. Consistently, the beta-strand-1 substitution greatly destabilized the 'PIN' conformation of TC binding to reconstituted 43S.mRNA complexes in vitro. Other substitutions in beta-hairpin loop residues increased initiation fidelity and destabilized PIN at UUG, but not AUG start codons. We conclude that the Rps5 beta-hairpin is as crucial as soluble initiation factors for efficient and accurate start codon recognition. PMID- 26134897 TI - miR-135 family members mediate podocyte injury through the activation of Wnt/beta catenin signaling. AB - The upregulation of Wnt/beta-catenin signaling occurs in virtually all types of kidney disease and is associated with podocyte injury. However, the precise mechanisms involved in the development of kidney disease remain to be elucidated. MicroRNAs (miRNAs or miRs) are a class of short non-coding RNAs and they have been shown to be regulators of gene expression, mainly by binding to the untranslated region (UTR) of mRNAs. The aim of the present study was to determine the role of the 2 members of the miR-135 family (miR-135a and miR-135b) in podocyte injury and to elucidate the mechanisms responsible for the damage to podocytes. The results revealed that miR-135a and miR-135b were upregulated in models of podocyte injury and in glomeruli isolated from patients with focal segmental glomerulosclerosis (FSGS). The ectopic expression of miR-135a and miR 135b led to severe podocyte injury and the disorder of the podocyte cytoskeleton. Our findings demonstrated that miR-135a and miR-135b activated Wnt/beta-catenin signaling and induced the nuclear translocation of beta-catenin. Using luciferase reporter assays, reverse transcription-quantitative polymerase chain reaction (RT qPCR) and western blot analysis, glycogen synthase kinase 3beta (GSK3beta) was identified as a target gene of miR-135a and miR-135b. To the best of our knowledge, this is the first study to demonstrate that members of the miR-135 family (specifically miR-135a and miR-135b) regulate the expression of GSK3beta, thus playing a role in the development of podocyte injury and the disorder of the podocyte cytoskeleton. This is an important finding as it may contribute to the development of novel therapeutics for podocyte injury-associated glomerulopathies. PMID- 26134898 TI - An ALS disease mutation in Cdc48/p97 impairs 20S proteasome binding and proteolytic communication. AB - Cdc48 (also known as p97 or VCP) is an essential and highly abundant, double-ring AAA+ ATPase, which is ubiquitous in archaea and eukaryotes. In archaea, Cdc48 ring hexamers play a direct role in quality control by unfolding and translocating protein substrates into the degradation chamber of the 20S proteasome. Whether Cdc48 and 20S cooperate directly in protein degradation in eukaryotic cells is unclear. Two regions of Cdc48 are important for 20S binding, the pore-2 loop at the bottom of the D2 AAA+ ring and a C-terminal tripeptide. Here, we identify an aspartic acid in the pore-2 loop as an important element in 20S recognition. Importantly, mutation of this aspartate in human Cdc48 has been linked to familial amyotrophic lateral sclerosis (ALS). In archaeal or human Cdc48 variants, we find that mutation of this pore-2 residue impairs 20S binding and proteolytic communication but does not affect the stability of the hexamer or rates of ATP hydrolysis and protein unfolding. These results suggest that human Cdc48 interacts functionally with the 20S proteasome. PMID- 26134899 TI - Reproductive and Metabolic Responses of Early-lactating Dairy Cows Fed Different Dietary Protein Sources. AB - Optimal reproduction is very closely tied with optimal nutrition, and early lactation diets in cows are critical to successful reproduction and monitoring is important. To evaluate the effects of different dietary protein sources on metabolic parameters and reproductive activity, a total of 36 Italian Friesian early-lactating dairy cows were assigned for 16 weeks to three dietary treatments as follow: the control diet contained soya bean meal (SBM) as the main protein source, whereas the experimental diets contained faba bean (FB) or pea seeds (PS) as alternative protein sources. Diets were formulated to be isocaloric and isonitrogenous. Cow blood samples were collected, and plasma were analysed for metabolites, biological enzymes, beta-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA). Feeding alternative protein sources had no effects on most metabolic blood profile, except for blood cholesterol, triglycerides and urea. Results from reproductive parameters indicated that cows fed FB diet had a lower insemination index, but a shorter calving to conception period and an improved conception rate and artificial insemination outcome, when compared to cows fed SBM or PS diets. It can be concluded that replacing conventional dietary SBM with alternative protein sources, especially FB, resulted in improved reproductive performances and metabolic parameters in early-lactating dairy cows. PMID- 26134900 TI - Electron-Hole Confinement Symmetry in Silicon Quantum Dots. AB - We report electrical transport measurements on a gate-defined ambipolar quantum dot in intrinsic silicon. The ambipolarity allows its operation as either an electron or a hole quantum dot of which we change the dot occupancy by 20 charge carriers in each regime. Electron-hole confinement symmetry is evidenced by the extracted gate capacitances and charging energies. The results demonstrate that ambipolar quantum dots offer great potential for spin-based quantum information processing, since confined electrons and holes can be compared and manipulated in the same crystalline environment. PMID- 26134901 TI - OneBac 2.0: Sf9 Cell Lines for Production of AAV5 Vectors with Enhanced Infectivity and Minimal Encapsidation of Foreign DNA. AB - Scalable production of recombinant adeno-associated virus vectors (rAAV) in baculovirus-infected Sf9 cells yields high burst sizes but variable infectivity rates per packaged AAV vector genome depending on the chosen serotype. Infectivity rates are particularly low for rAAV5 vectors, based on the genetically most divergent AAV serotype. In this study we describe key improvements of the OneBac system for the generation of rAAV5 vectors, whose manufacturing has been unsatisfactory in all current insect cell-based production systems. The Sf9 cell-based expression strategy for AAV5 capsid proteins was modified to enhance relative AAV5 VP1 levels. This resulted in a 100-fold boost of infectivity per genomic AAV5 particle with undiminished burst sizes per producer cell. Furthermore, the issue of collateral packaging of helper DNA into AAV capsids was approached. By modifications of the AAV rep and cap expression constructs used for the generation of stable Sf9 cell lines, collateral packaging of helper DNA sequences during rAAV vector production was dramatically reduced down to 0.001% of packaged rAAV genomes, while AAV5 burst sizes and infectivity rates were maintained. OneBac 2.0 represents the first insect cell-based scalable production system for high per-particle AAV5 infectivity rates combined with minimal collateral packaging of helper DNA, allowing the manufacturing of safe AAV5-based gene therapies for clinical application. PMID- 26134902 TI - Lectin-Magnetic Beads for Plasma Membrane Isolation. AB - Plasma membrane proteins mainly function to transmit external signals into the cell. Many plasma membrane receptor tyrosine kinases (e.g., HER2 and EGFR) are known to mediate oncogenic progression, making them prime targets for cancer therapy. Recently, it has become important to identify plasma membrane proteins that are differentially expressed in normal versus cancer cells, in drug sensitive versus drug-resistant cells, or among tumor cells that metastasize to different organ sites because these differentially expressed membrane proteins may lead to the identification of therapeutic targets or diagnostic markers. In addition, there is an increased interest in identifying cell-surface proteins that could serve as markers for stem cells, progenitor cells, or cells of different lineages. Traditionally, membrane isolation requires multiple centrifugation steps to isolate different organelles based on their density. With the advent of affinity matrix technology, it is possible to separate organelles based on their molecular differences. A defining characteristic of the plasma membrane is that plasma membrane proteins are more extensively glycosylated than are intracellular membrane proteins. As a result, affinity chromatography employing lectin, a carbohydrate-binding protein, is commonly used to isolate plasma membrane proteins. We have extended this concept for plasma membrane isolation by using concanavalin A (ConA), a lectin with mannose specificity. Here we describe a protocol that uses immobilized ConA bound to magnetic beads to isolate plasma membranes from homogenized cell lysates. The captured plasma membrane proteins are then solubilized from the ConA-magnetic beads by detergents in the presence of a competing sugar, methyl alpha-mannopyranoside. PMID- 26134903 TI - Reconstitution of Mice with Modified Hematopoietic Stem Cells. AB - Stem cell transplantation is well established in humans for the treatment of hematopoietic disease, including hematopoietic malignancies. Similar direct transplant procedures can readily be performed in mice; these procedures can be paired with retroviral infection to introduce exogenous genes or to silence endogenous genes in a subset of cells in the murine hematopoietic system. The resulting mice are chimeric for cells bearing a specific alteration. This approach has the advantage of examining tumorigenesis on a largely wild-type background (if only a subset of cells are infected), a situation that more accurately parallels the human situation. Additionally, tumor development occurs within the appropriate native microenvironment. Here, we describe the isolation and retroviral infection of hematopoietic stem cells (HSCs), as well as the reconstitution and monitoring of tumor formation in lethally irradiated recipient mice. This protocol requires a source of long-term HSCs; these can include either stimulated adult bone marrow or fetal liver-the site of primitive hematopoiesis. PMID- 26134904 TI - Reconstitution of Mice with Modified Liver Stem Cells. AB - Hepatic progenitor cells isolated from fetal liver can be transplanted into recipient mice to reconstitute an organ system. Retroviral infection can be used to introduce putative oncogenes or short-hairpin RNAs (shRNAs) targeting putative tumor suppressors into the cells; reconstituted mice then develop livers that are chimeric for cells bearing a specific alteration. This approach has the advantage of examining tumorigenesis on a largely wild-type background (if only a subset of cells are infected), a situation that more accurately parallels the human situation. Additionally, tumor development occurs within the appropriate native microenvironment. Here, we describe the isolation of hepatic progenitor cells, as well as the reconstitution and tumor monitoring of recipient mice. PMID- 26134905 TI - Boundary Analysis to Determine the Minimal RNA Sequence Required for Protein Binding. AB - Boundary analysis is a powerful and often overlooked method for determining the sequences within an RNA molecule that are required for a specific RNA-protein interaction. In this approach, 5'- and 3'-end-labeled RNAs are fragmented randomly (usually by limited alkaline hydrolysis, but nuclease fragmentation can also be used) such that a ladder of fragments covering the whole molecule of interest is produced. This mixture of fragments is then allowed to bind to the protein (or other molecule) of interest. Bound fragments are selected by affinity or antibody binding and then displayed on a gel. The point at which banding is lost for 5'-end-labeled RNAs defines the 3' boundary of the binding site, and the point at which banding is lost for 3'-end-labeled RNAs defines the 5' boundary of the binding site. PMID- 26134906 TI - Hi-C in Budding Yeast. AB - Hi-C enables simultaneous detection of interaction frequencies between all possible pairs of restriction fragments in the genome. The Hi-C method is based on chromosome conformation capture (3C), which uses formaldehyde cross-linking to fix chromatin regions that interact in three-dimensional space, irrespective of their genomic locations. In the Hi-C protocol described here, cross-linked chromatin is digested with HindIII and the ends are filled in with a nucleotide mix containing biotinylated dCTP. These fragments are ligated together, and the resulting chimeric molecules are purified and sheared to reduce length. Finally, biotinylated ligation junctions are pulled down with streptavidin-coated beads, linked to high-throughput sequencing adaptors, and amplified via polymerase chain reaction (PCR). The resolution of the Hi-C data set will depend on the depth of sequencing and choice of restriction enzyme. When sufficient sequence reads are obtained, information on chromatin interactions and chromosome conformation can be derived at single restriction fragment resolution for complete genomes. PMID- 26134907 TI - Analyzing the Response of RNAi-Treated Drosophila Cells to Death Stimuli by Quantitative Real-Time Polymerase Chain Reaction. AB - A useful complement to animal studies is the use of Drosophila cell lines to analyze cell-death responses. There are numerous Drosophila cell lines available, such as S2 cells, which possess the advantages of being semi-adherent, fast growing, relatively robust, and useful for transfection and knockdown studies, whereas other lines, such as mbn2, are more suitable for analyzing hormone induced cell death and gene expression. Drosophila cell lines are very amenable to knockdown studies as the cells take up double-stranded RNA (dsRNA) from the medium, initiating gene silencing and resulting in a high level of gene knockdown. This means that the cell lines are useful for investigating the response to death stimuli, following gene knockdown, by examining the expression of cell-death genes. This protocol describes the synthesis of dsRNA for treatment of Drosophila cells and the subsequent analysis of cell-death gene expression by quantitative real-time polymerase chain reaction (qPCR). PMID- 26134908 TI - Using Synthetic Peptide Substrates to Measure Drosophila Caspase Activity. AB - Central to the apoptotic pathway is the activation of caspases that are members of a highly conserved family of cysteine proteases. Caspases are synthesized as inactive zymogens and are generally activated by proteolytic cleavage to form the catalytically active enzyme. Caspase activity in apoptotic cells can be measured by assessing the cleavage of commercially available synthetic caspase substrates. The synthetic substrates contain a caspase cleavage site conjugated to a fluorochrome, such as 7-amino-4-methylcoumarin (AMC), or a chromophore, such as p nitroaniline (pNA), for colorimetric detection. Here, we present a protocol for the measurement of caspase activity in Drosophila cell extracts by cleavage of the target peptide in the synthetic substrate that releases a fluorochrome or color-producing agent. The signal is measured by a spectrophotometer, with the intensity of the signal being proportional to the amount of substrate cleaved. PMID- 26134910 TI - Fluorescent Calcium Indicator Protein Expression in the Mouse Brain Using Recombinant Adeno-Associated Viruses. AB - One method for gene delivery and long-term fluorescent calcium indicator protein (FCIP) expression in mammalian neurons in vivo involves the introduction of FCIPs via recombinant adeno-associated virus (rAAV) vectors using constitutive and cell type-specific promoters. This protocol describes the use of rAAVs to express FCIPs in the brain for imaging. Human embryonic kidney 293 cells are first transfected using calcium phosphate. rAAV is then prepared using either an iodixanol gradient or a heparin column. After the virus is purified, its quality is assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, estimation of genomic and functional virus titers by quantitative polymerase chain reaction, and expression in dissociated neurons. Mice are injected with rAAV using a stereotactic instrument and can be imaged ~3 wk later. PMID- 26134909 TI - Fluorescent Calcium Indicator Protein Expression in the Brain Using Tetracycline Responsive Transgenic Mice. AB - To achieve robust long-term fluorescent calcium indicator protein (FCIP) expression in mammalian neurons in vivo, classical mouse transgenesis by pronuclear DNA injection using tetracycline (Tet)-controlled genetic switches can be deployed. This protocol describes methods for regulated expression of FCIP using Tet-responsive transgenic mice. The Tet-inducible system requires three components for inducible and reversible control of gene expression: (1) a potent transcriptional activator protein, either Tet transactivator (tTA) or reverse tTA (rtTA); (2) a minimal Tet-promoter (P(tet)) or a bidirectional Tet-promoter (P(tet)bi) to express one or more responder genes; and (3) Tet or one of its derivatives such as doxycycline (Dox) as an inducer. To ensure a high level of FCIP expression in neurons, transgenic founder mice are screened using an ear fibroblast culture method to identify those that are responsive to Dox treatment before use in experiments. The protocol describes the use of Dox to regulate gene expression and provides a short description of in vivo recording of luciferase activity. PMID- 26134911 TI - Studying Apoptosis in Drosophila. AB - The apoptotic machinery is highly conserved throughout evolution, and central to the regulation of apoptosis is the caspase family of cysteine proteases. Insights into the regulation and function of apoptosis in mammals have come from studies using model organisms. Drosophila provides an exceptional model system for identifying the function of conserved mechanisms regulating apoptosis, especially during development. The characteristic patterns of apoptosis during Drosophila development have been well described, as has the apoptotic response following DNA damage. The focus of this discussion is to introduce methodologies for monitoring apoptosis during Drosophila development and also in Drosophila cell lines. PMID- 26134912 TI - Measuring Chromatin Structure in Budding Yeast. AB - Chromosome conformation capture (3C) has revolutionized the ways in which the conformation of chromatin and its relationship to other molecular functions can be studied. 3C-based techniques are used to determine the spatial arrangement of chromosomes in organisms ranging from bacteria to humans. In particular, they can be applied to the study of chromosome folding and organization in model organisms with small genomes and for which powerful genetic tools exist, such as budding yeast. Studies in yeast allow the mechanisms that establish or maintain chromatin structure to be analyzed at very high resolution with relatively low cost, and further our understanding of these fundamental processes in higher eukaryotes as well. Here we provide an overview of chromatin structure and introduce methods for performing 3C, with a focus on studies in budding yeast. Variations of the basic 3C approach (e.g., 3C-PCR, 5C, and Hi-C) can be used according to the scope and goals of a given experiment. PMID- 26134913 TI - Imaging Live Cells Using Quantum Dots. AB - Quantum dots (QDs) are nanoparticles with fluorescent properties that offer advantages over organic fluorophores. As a result, QDs have found wide application in biological imaging. In this introduction we discuss the approaches for using QDs for labeling and imaging individual cells and cellular processes in live cells both in vivo and in culture. PMID- 26134914 TI - Core curriculum illustration: pediatric traumatic spondylolisthesis of the axis. AB - This is the 16th installment of a series that will highlight one case per publication issue from the bank of cases available online as part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online, please visit the ASER Core Curriculum and Recommendations for Study online at http://www.aseronline.org/curriculum/toc.htm. PMID- 26134915 TI - The cystic duct knot sign: case report with description of a new ultrasound sign of gallbladder torsion. AB - Gallbladder torsion or volvulus is a rare but potentially lethal entity. We report the imaging findings of gallbladder torsion and describe a potentially novel ultrasound sign for the preoperative diagnosis of torsion. An 87-year-old woman presented with a 4-day history of right upper quadrant pain. An initial right upper quadrant ultrasound exam demonstrated cholelithiasis and findings of acute cholecystitis which included gallbladder distension, wall thickening, trace pericholecystic fluid, and a positive sonographic Murphy's sign. Gallbladder torsion was prospectively diagnosed on the subsequent contrast-enhanced CT scan of the abdomen based upon the abnormal transverse orientation of the gallbladder with the neck directed laterally. Ultrasound images were reviewed and a "knot" like hyperechoic nodular appearance of the torsed cystic duct close to the gallbladder neck was clearly apparent. Prospective identification of the torsed cystic duct may prompt the ultrasound diagnosis of gallbladder torsion. PMID- 26134916 TI - Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies. AB - OBJECTIVE: To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents. METHODS: The Cardiff model was populated with data synthesized from three head-to-head randomized clinical trials of up to 30 weeks in China comparing exenatide BID vs insulin glargine as add-on therapies to oral therapies in the Chinese population. The Cardiff model generated outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs, and quality-adjusted life years (QALYs). Cost and QALYs were estimated with a time horizon of 40 years at a discount rate of 3% from a societal perspective. RESULTS: Compared with insulin glargine plus OAD treatments, patients on exenatide BID plus OAD gained 1.88 QALYs, at an incremental cost saving of Chinese Renminbi (RMB) 114,593 (i.e., cost saving of RMB 61078/QALY). The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis. The variables with the most impact on incremental cost-effectiveness ratio included HbA1c level at baseline, health utilities decrement, and BMI at baseline. CONCLUSIONS: Compared with insulin glargine QD, exenatide BID as add-on therapy to OAD is a cost-effective treatment in Chinese patients inadequately controlled by OAD treatments. PMID- 26134917 TI - Prevalence and healthcare costs of obesity-related comorbidities: evidence from an electronic medical records system in the United States. AB - OBJECTIVE: This study estimated the economic burden of obesity-related comorbidities (ORCs) in the US, at both the person and population levels. METHODS: The Geisinger Health System provided electronic medical records and claims between January 2004 and May 2013 for a sample of 153,561 adults (50% males and 97% white). Adults with < 2 years of data, who were underweight (body mass index (BMI) < 18.5 kg/m(2)), or had diseases causing major weight change (e.g., malignancy) during the study period (i.e., continuous enrollment in health plans) were excluded. A total of 21 chronic conditions, with established association with obesity in the literature, were identified by diagnosis codes and/or lab test results. The total healthcare costs were measured in each year. The association between annual costs and ORCs was assessed by a regression, which jointly considered all the ORCs. The per-person incremental costs of a single comorbidity, without any of the other ORCs, were calculated. The population-level economic burden was the product of each ORC's incremental costs and the annual prevalence of the ORC among 100,000 individuals. The prevalence of ORCs was stratified by obesity status to estimate the economic burden among 100,000 individuals with obesity and among those without. RESULTS: This study identified 56,895 adults (mean age = 47 years; mean BMI = 29.6 kg/m(2)). The annual prevalence of ORCs ranged from 0.5% for pulmonary embolism (PE) to 41.8% for dyslipidemia. The per-person annual incremental costs of a single ORC ranged from $120 for angina to $1665 for PE. Hypertensive diseases (HTND), dyslipidemia, and osteoarthritis were the three most expensive ORCs at the population level; each responsible for >=$18 million annually among 100,000 individuals. HTND and osteoarthritis were much more costly among individuals with obesity than those without obesity. LIMITATIONS: Data were from a small geographic region. CONCLUSIONS: ORCs are associated with substantial economic burden, especially for those requiring continuous treatments. PMID- 26134918 TI - DNA Elasticity from Short DNA to Nucleosomal DNA. AB - Active biological processes like transcription, replication, recombination, DNA repair, and DNA packaging encounter bent DNA. Machineries associated with these processes interact with the DNA at short length (<100 base pair) scale. Thus, the study of elasticity of DNA at such length scale is very important. We use fully atomistic molecular dynamics (MD) simulations along with various theoretical methods to determine elastic properties of dsDNA of different lengths and base sequences. We also study DNA elasticity in nucleosome core particle (NCP) both in the presence and the absence of salt. We determine stretch modulus and persistence length of short dsDNA and nucleosomal DNA from contour length distribution and bend angle distribution, respectively. For short dsDNA, we find that stretch modulus increases with ionic strength while persistence length decreases. Calculated values of stretch modulus and persistence length for DNA are in quantitative agreement with available experimental data. The trend is opposite for NCP DNA. We find that the presence of histone core makes the DNA stiffer and thus making the persistence length 3-4 times higher than the bare DNA. Similarly, we also find an increase in the stretch modulus for the NCP DNA. Our study for the first time reports the elastic properties of DNA when it is wrapped around the histone core in NCP. We further show that the WLC model is inadequate to describe DNA elasticity at short length scale. Our results provide a deeper understanding of DNA mechanics and the methods are applicable to most protein-DNA complexes. PMID- 26134919 TI - Metastatic castration-resistant prostate cancer: targeting the mechanisms of resistance to abiraterone acetate and enzalutamide. AB - Persistent androgen receptor (AR) axis is a functionally important pathway for prostate cancer cells and it is currently regarded as a critical therapeutic target. Although the impressive clinical activity of new hormonal agents, such as the second-generation AR antagonist enzalutamide (formerly MDV3100) and the selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone acetate (AA), in patients with metastatic castration-resistant prostate cancer (mCRPC), innate or acquired resistance invariably arises. To date, emerging hypotheses are different, but the mechanisms of resistance to these drugs have not yet been clarified. The aim of this review is to summarize the main data available on the evaluation of the multiple levels of development of resistance to next-generation AR-directed therapies. Understanding how the AR is activated may have clinical implications in defining which patients will respond to existing therapeutic agents and provide a proof for making novel strategies. PMID- 26134920 TI - Thiophene-Diketopyrrolopyrrole-Based Quinoidal Small Molecules as Solution Processable and Air-Stable Organic Semiconductors: Tuning of the Length and Branching Position of the Alkyl Side Chain toward a High-Performance n-Channel Organic Field-Effect Transistor. AB - A series of thiophene-diketopyrrolopyrrole-based quinoidal small molecules (TDPPQ 2-TDPPQ-5) bearing branched alkyl chains with different side-chain lengths and varied branching positions are synthesized. Field-effect transistor (FET) measurement combined with thin-film characterization is utilized to systematically probe the influence of the side-chain length and branching position on the film microstructure, molecular packing, and, hence, charge transport property. All of these TDPPQ derivatives show air-stable n-channel transporting behavior in spin-coated FET devices, which exhibit no significant decrease in mobility even after being stored in air for 2 months. Most notably, TDPPQ-3 exhibits an outstanding n-channel semiconducting property with electron mobilities up to 0.72 cm(2) V(-1) s(-1), which is an unprecedented value for spin coated DPP-based n-type semiconducting small molecules. A balance of high crystallinity, satisfactory thickness uniformity and continuity, and strong intermolecular interaction accounts for the superior charge-transport characteristics of TDPPQ-3 films. Our study demonstrates that tuning the length and branching position of alkyl side chains of semiconducting molecules is a powerful strategy for achieving high FET performance. PMID- 26134922 TI - Directed Magnetic Particle Transport above Artificial Magnetic Domains Due to Dynamic Magnetic Potential Energy Landscape Transformation. AB - An approach for a remotely controllable transport of magnetic micro- and/or nanoparticles above a topographically flat exchange-bias (EB) thin film system, magnetically patterned into parallel stripe domains, is presented where the particle manipulation is achieved by sub-mT external magnetic field pulses. Superparamagnetic core-shell particles are moved stepwise by the dynamic transformation of the particles' magnetic potential energy landscape due to the external magnetic field pulses without affecting the magnetic state of the thin film system. The magnetic particle velocity is adjustable in the range of 1-100 MUm/s by the design of the substrate's magnetic field landscape (MFL), the particle-substrate distance, and the magnitude of the applied external magnetic field pulses. The agglomeration of magnetic particles is avoided by the intrinsic magnetostatic repulsion of particles due to the parallel alignment of the particles' magnetic moments perpendicular to the transport direction and parallel to the surface normal of the substrate during the particle motion. The transport mechanism is modeled by a quantitative theory based on the precise knowledge of the sample's MFL and the particle-substrate distance. PMID- 26134921 TI - Curcumin induces apoptosis and suppresses invasion through MAPK and MMP signaling in human monocytic leukemia SHI-1 cells. AB - CONTEXT: Curcumin is a polyphenolic compound extracted from rhizomes of the tropical plant Curcuma longa L. (Zingiberaceae) and it has antitumor, antioxidative, and anti-inflammatory effects. However, its effects on leukemia cell proliferation and invasion are not clear. OBJECTIVE: This study investigates the effects of curcumin on acute monocytic leukemia SHI-1 cells at the molecular level. MATERIALS AND METHODS: The effects of SHI-1 cells treated with 6.25-25 MUM curcumin for 12-48 h were measured by MTT assay, flow cytometry, and Matrigel transwell assay; the underlying molecular mechanisms were assessed by quantitative PCR, Western blotting, and gelatin zymography. RESULTS: Treatment of SHI-1 cells with curcumin inhibited cell proliferation in a dose- and time dependent manner, and the IC50 values at 12, 24, and 48 h were 32.40, 14.13, and 9.67 MUM. Curcumin inhibited SHI-1 cell proliferation by arresting the cells in the S-phase, increasing the number of Annexin V-FITC(+)/PI(-) cells and promoting the loss of ?Psim. The results of PCR and Western blotting showed that curcumin increased the FasL mRNA level; inhibited Bcl-2, NF-kappaB, and ERK expression; and activated P38 MAPK, JNK, and caspase-3. Additionally, curcumin partially suppressed SHI-1 cell invasion and attenuated the mRNA transcription and secretion of MMP-2 and MMP-9. DISCUSSION AND CONCLUSION: This study demonstrates that curcumin not only induces SHI-1 cell apoptosis, possibly via both intrinsic and extrinsic pathways triggered by JNK, P38 MAPK and ERK signaling, but also partially suppresses SHI-1 cell invasion, likely by reducing the levels of transcription and secretion of MMP-2 and MMP-9. PMID- 26134923 TI - A pH-responsive fluorescent [5]pseudorotaxane formed by self-assembly of cationic water-soluble pillar[5]arenes and a tetraphenylethene derivative. AB - The formation of a pH-responsive fluorescent [5]pseudorotaxane by self-assembly of cationic water-soluble pillar[5]arenes and a tetraphenylethene derivative was reported. PMID- 26134924 TI - Development, optimization, and characterization of polymeric electrospun nanofiber: a new attempt in sublingual delivery of nicorandil for the management of angina pectoris. AB - The objective of the current investigation was to develop a novel biocomposite polymeric nanofiber for sublingual delivery of nicorandil in an attempt to reduce mucosal ulceration and to improve drug bioavailability. Polymeric nanofibers were achieved using vitamin B12 and a blend of hyaluronic acid and polyvinyl alcohol as polymeric constituents. The electrospinning method was used to prepare drug (nicorandil)-loaded nanofibers. The resulting nanofibers were characterized for morphology, drug loading, XRD, DSC, in vitro drug release, degree of swelling, and pharmacokinetic behavior. The prepared nanofibers were found to be uniform, non-beaded, and non-woven, with fiber diameter ranging from 200-450 nm. In vitro drug release substantiated the controlled release behavior of the developed formulation. Histopathology studies demonstrated no evidence of mucosal ulceration at the site of application. Pharmacokinetic studies established the preclinical safety and showed the maintenance of an effective therapeutic level for a prolonged period. The present investigation gives inputs showing that the biocomposite nanofiber assists as a perfect carrier system for sublingual delivery of anti-anginal drugs. PMID- 26134925 TI - In vitro and in vivo evaluation of PEGylated nanoparticles of bendamustine for treatment of lung cancer. AB - The purpose of this study was to develop PEGylated nanoparticles of bendamustine (BM) to improve therapeutic efficiency of drug and reduce the side-effects. The nanoparticles were prepared by a modified diffusion-emulsification method. The particle size and zeta potential of optimized BM-loaded PEGylated NPs were found to be 256 nm and -29.1 mV. The in vitro release showed biphasic behavior, with initial burst release followed by slow sustained delivery. The anti-tumor activity was determined using the A- 549 cell line, by the MTT assay. The stability study revealed that the nanoparticles prepared were stable for 3 months at both 25 degrees C and 4 degrees C. PMID- 26134926 TI - Evaluating the safety of Liptruzet (ezetimibe and atorvastatin): what are the potential benefits beyond low-density lipoprotein cholesterol-lowering effect? AB - INTRODUCTION: The combination of ezetimibe and atorvastatin (Liptruzet - referred to in this article as eze/ator), has recently been approved by the FDA for reducing low-density lipoprotein cholesterol (LDL-c) in patients with primary or mixed hyperlipidemia as in case of homozygous familial hypercholesterolemia. It helps block intestinal absorption of cholesterol and it inhibits the production of cholesterol in the liver. AREAS COVERED: The safety and effectiveness of the eze/ator combination as treatment of hyperlipidemia. Medline was searched for atorvastatin and/or ezetimibe. EXPERT OPINION: The combination of (eze/ator) is proven to be effective in lowering LDL-c. It is not only a safe and effective treatment of hyperlipidemia, but it also reduces inflammatory markers and atherosclerosis. It is not yet clear, however, whether the combination therapy can decrease the risk of diabetes associated with statin administration. Insulin sensitivity is improved by the single administration of ezetimibe, a finding that is documented by several clinical and animal studies. More specifically, ezetimibe has been shown to decrease insulin resistance associated with nonalcoholic fatty liver disease (NAFLD). The effects of combination therapy that have to be explored in future research and clinical trials include whether this combination can be used in the treatment of NAFLD, cholesterol gallstones and portal hypertension. PMID- 26134927 TI - Framework for systematic identification of ethical aspects of healthcare technologies: the SBU approach. AB - OBJECTIVES: Assessment of ethical aspects of a technology is an important component of health technology assessment (HTA). Nevertheless, how the implementation of ethical assessment in HTA is to be organized and adapted to specific regulatory and organizational settings remains unclear. The objective of this study is to present a framework for systematic identification of ethical aspects of health technologies. Furthermore, the process of developing and adapting the framework to a specific setting is described. METHODS: The framework was developed based on an inventory of existing approaches to identification and assessment of ethical aspects in HTA. In addition, the framework was adapted to the Swedish legal and organizational healthcare context, to the role of the HTA agency and to the use of non-ethicists. The framework was reviewed by a group of ethicists working in the field as well as by a wider set of interested parties including industry, interest groups, and other potential users. RESULTS: The framework consists of twelve items with sub-questions, short explanations, and a concluding overall summary. The items are organized into four different themes: the effects of the intervention on health, its compatibility with ethical norms, structural factors with ethical implications, and long term ethical consequences of using the intervention. CONCLUSIONS: In this study, a framework for identifying ethical aspects of health technologies is proposed. The general considerations and methodological approach to this venture will hopefully inspire and present important insights to organizations in other national contexts interested in making similar adaptations. PMID- 26134928 TI - Large-Scale Nanophotonic Solar Selective Absorbers for High-Efficiency Solar Thermal Energy Conversion. AB - An omnidirectional nanophotonic solar selective absorber is fabricated on a large scale using a template-stripping method. The nanopyramid nickel structure achieves an average absorptance of 95% at a wavelength range below 1.3 MUm and a low emittance less than 10% at wavelength >2.5 MUm. PMID- 26134929 TI - miR-99b promotes metastasis of hepatocellular carcinoma through inhibition of claudin 11 expression and may serve as a prognostic marker. AB - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, mainly due to its high rates of postoperative recurrence and metastasis. Moreover, there is no widely accepted prognostic marker of recurrence. Therefore, the aim of the present study was to determine whether such a marker could be provided by a microRNA (miRNA), since recent evidence indicates that miRNAs are important contributors to the metastatic phenotype. In the present study, we showed that miR-99b was expressed at high levels in tissues of patients with HCC and in cell lines derived from HCCs. Elevated levels of miR-99b predicted poor overall survival as well as disease-free survival of patients with HCC. Moreover, miR-99b expression levels correlated with capsule formation and microvascular invasion, which are required for postoperative recurrence. Overexpression or knockdown of miR-99b expression increased or inhibited, respectively, the metastasis of HCC cells in vitro. Furthermore, using a dual luciferase assay, we demonstrated that miR-99b inhibited the expression of claudin 11 (CLDN11), a component of tight junction strands by directly targeting the 3'-untranslated region of CLDN11 mRNA. In addition, CLDN11 expression was increased or decreased when miR-99b expression was inhibited or elevated in the HCC cells, respectively. Moreover, the expression of miR-99b was inversely correlated with CLDN11 mRNA or CLDN11 levels in the HCC tissues. These findings suggest that a high level of miR-99b expression is an independent prognostic factor and correlates with poor survival of patients with HCC. Therefore, inhibition of miR-99b expression may serve as a therapeutic approach for inhibiting the metastatic phenotype of HCC. PMID- 26134930 TI - Anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of beta-sitosterol and lupeol isolated from Diospyros lotus L. AB - In this study, the anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of beta-sitosterol (1) and lupeol (2), isolated from Diospyros lotus L., were explored. Compound 1 showed a marked concentration dependent inhibition against 12-O-tetradecanoylphorbol-13-acetate (20 ng/32 pmol) induced Epstein-Barr virus early antigen activation in Raji cells with IC50 of 270 MUg/ml, without significant toxicity (70% viability). Compound 2 showed significant anti-tumour-promoting effect with IC50 of 412 MUg/ml, without significant toxicity (60% viability). In heat-induced protein denaturation assay, compound 1 exhibited a concentration-dependent attenuation with a maximum effect of 73.5% at 500 MUg/ml with EC50 of 117 MUg/ml, while compound 2 exhibited a maximum effect of 59.2% at 500 MUg/ml with EC50 of 355 MUg/ml. Moreover, in silico docking studies against the phosphoinositide 3-kinase enzyme also show the inhibitory potency of these compounds. In short, both the compounds exhibited a marked anti-tumour-promoting and potent inhibitory effect on thermal-induced protein denaturation. PMID- 26134931 TI - Silica phytoliths in angiosperms: phylogeny and early evolutionary history. PMID- 26134932 TI - Regeneration or replacement? A case report and review of literature. AB - Endodontic treatment of immature necrotic teeth is a real challenge. Recently, a biologically based treatment strategy, referred to as regeneration, has been introduced. Tissue regeneration requires the presence of stems cells, a scaffold, and growth factors. Endodontic regeneration may improve the prognosis of immature necrotic teeth by re-establishing the functional pulpal tissue and further development of the root. However, the tissue formed in the pulpal space may not be original pulp tissue, and in some cases, it may result in uncontrolled calcification of the pulp. This study reports a case of successful endodontic regeneration and compares this process with the normal development of the contralateral tooth. Finally, it discusses the nature of the tissue formed during endodontic regeneration. PMID- 26134933 TI - Detection of Lyme Disease and Q Fever Agents in Wild Rodents in Central Italy. AB - The maintenance of tick-borne disease agents in the environment strictly depends on the relationship between tick vectors and their hosts, which act as reservoirs for these pathogens. A pilot study aimed to investigate wild rodents as reservoirs for zoonotic tick-borne pathogens (Borrelia burgdorferi sensu lato (s.l.), Coxiella burnetii, Francisella tularensis, and Anaplasma phagocytophilum) was carried out in an area of Gran Sasso e Monti della Laga National Park (Abruzzi Region, central Italy), a wide protected area where, despite sporadic reports of infection in humans and animals, eco-epidemiological data on these diseases are still not available. Rodents were trapped and released at the capture site after the collection of feeding ticks and blood samples. In all, 172 ticks were collected; the most frequent species was Ixodes acuminatus (53%). Out of 88 tick pools, 11 resulted positive for C. burnetii and 13 for B. burgdorferi s.l.; the Borrelia afzelii genospecies was identified in one Ixodes ricinus tick collected from one Apodemus sp. rodent. Out of 143 blood samples, seven Apodemus spp. and five Myodes glareolus were positive for B. burgdorferi s.l. and two Apodemus spp. were positive for C. burnetii. All samples (ticks and blood) were negative for F. tularensis and A. phagocytophilum. This is the first report of B. burgdorferi s.l. in the environment for Abruzzi Region. Data on the presence of B. burgdorferi s.l. are similar to that observed in other Mediterranean countries. The present work is also the first report of C. burnetii in wild rodents in Italy. C. burnetii infection has been largely investigated in Italy in ruminant farms by serology and molecular methods, but information on ecology and on the wild cycle are still lacking. Further studies including genotyping should be performed and species-specific differences between wild rodent reservoirs of Q fever and Lyme disease agents should be investigated. PMID- 26134935 TI - Cochlear Implantation in Children with Congenital and Noncongenital Unilateral Deafness. PMID- 25627680 TI - Does chewing gum improve recovery after an abdominal surgery?--First update. AB - This Living FRISBEE (Living FRIendly Summary of the Body of Evidence using Epistemonikos) is an update of the summary published in November 2014, based on four new systematic reviews published since then. Postoperative ileus is common condition that delays recovery after an abdominal surgery. Early use of sham feeding with chewing gum stimulates peristalsis and would allow an earlier nutrition. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified 18 systematic reviews including 81 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded that chewing gum probably reduces the length of hospital stay after an abdominal surgery. PMID- 26134936 TI - The Prevalence of Cochlear Obliteration After Labyrinthectomy Using Magnetic Resonance Imaging and the Implications for Cochlear Implantation. AB - OBJECTIVES: The aim of this study was to determine the prevalence of cochlear obliteration after labyrinthectomy. STUDY DESIGN: Retrospective review of medical records. SETTING: Tertiary referral center. PATIENTS: Sixty-five patients who had previously undergone resection of an acoustic neuroma through a translabyrinthine approach. INTERVENTION: The magnetic resonance studies were analyzed as part of the routine surveillance after tumor resection. MAIN OUTCOME MEASURE: To determine whether the cochlear lumen remained fluid filled. RESULTS: Sixty-five cochleas were examined. Forty-four cochleas were patent and, of the remaining 21, 9 were obliterated and 12 were partially obliterated. The average length of follow-up for the patent, partially obliterated, and obliterated cochlea groups was 47, 29, and 77 months, respectively. CONCLUSION: Obliteration of the cochlea, either partially or completely, occurs in approximately one-third of patients. Time elapsed after labyrinthectomy did not seem to be a predictor of cochlear obliteration. PMID- 26134937 TI - Evaluation of Reported Malignant Transformation of Vestibular Schwannoma: De Novo and After Stereotactic Radiosurgery or Surgery. AB - OBJECTIVE: To critically analyze each reported case of malignant transformation of vestibular schwannoma (VS) after either stereotactic radiosurgery (SRS) or microsurgery (MS). DATA SOURCES: We searched the Pubmed/Medline database using the relevant key words vestibular schwannoma, acoustic neuroma, malignant, transformation, radiation, induced, stereotactic, radiosurgery, malignancy, GammaKnife, and CyberKnife and combinations thereof. STUDY SELECTION: Inclusion criteria for malignant transformation of VS after SRS included histopathology of initially benign VS, subsequent histopathology confirming malignant VS, reasonable latency period between malignancy and benign diagnoses. DATA EXTRACTION: A neurotologist and a skull base neurosurgeon independently assessed each case report for quality, entry, exclusion criteria, and comparability of extracted data. DATA SYNTHESIS: We calculated median age, latency times, and survival times for each case report. RESULTS: Malignant transformation has been documented to occur after either SRS or MS. Eight cases were included that showed histopathologic evidence of malignant transformation after SRS and MS. Four cases of malignant transformation were included that demonstrated malignant transformation after MS only. Malignant transformation of VS can also occur de novo, and de novo malignant VSs are also encountered, which can confound a causal inference from either SRS or MS. Eighteen cases of primary malignant VS were included. Studies that were identified but not included in the review are summarized and tabulated. We found 12 studies of malignant transformation associated with NF2. CONCLUSION: The potential mechanism leading to malignant transformation of VS seems more obvious for SRS and is less understood for MS. Given a low incidence of de novo malignant schwannoma, the possibility that these are spontaneous events in either setting cannot be ruled out. Risk of malignant transformation of VS after either SRS or MS is not zero; however, the magnitude of this risk is probably minimal based on the evidence from eight histopathologically confirmed cases. PMID- 26134938 TI - The Outcome of Cochlear Implantation for Mitochondrial Disease Patients With Syndromic Hearing Loss. AB - OBJECTIVES: To evaluate the outcome and to confirm the validity of cochlear implantation for syndromic deafness in patients with mitochondrial disease. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: We reviewed medical charts of 367 cochlear implantation cases at Kyoto University Hospital between 1987 and 2012. We identified five patients with syndromic mitochondrial disease who underwent cochlear implantation surgery. The mean age of the patients (four women and one man) when they underwent surgeries was 44.4 years (range, 30-64 yr; median, 41 yr). INTERVENTIONS: Therapeutic and rehabilitative. MAIN OUTCOME MEASURE: In four of five patients, speech perception performance was measured using Japanese vowels, consonant-vowel syllables, and short sentences. RESULTS: Only 1.4% (5 of 367) of cochlear implantation cases at Kyoto University Hospital underwent cochlear implantation surgery because of syndromic mitochondrial diseases. Four of those patients showed significantly improved speech perception outcomes, and the beneficial effects of the intervention continued long after surgery. One patient could not perform speech perception test presumably because of poor cognitive function. CONCLUSION: Mitochondrial disease patients who underwent cochlear implantation surgery sustained gains in hearing performance even long after surgery. A single patient showed poor postoperative speech perception associated with cognitive problems. Cochlear implantation for mitochondrial disease patients seems to be a viable treatment option in the absence of significant cognitive impairment. PMID- 26134939 TI - Efficacy of Computer-Controlled and Modified Roll Maneuver for Treatment of Geotropic Lateral Canal Benign Paroxysmal Positional Vertigo. AB - OBJECTIVE: To evaluate the short-term efficacy of computer-controlled and modified roll maneuver (CMRM) versus conventional roll maneuver (RM) for treatment of geotropic lateral canal benign paroxysmal positional vertigo (BPPV). STUDY DESIGN: Prospective case-controlled study. SETTING: Academic hospital. PATIENTS: One hundred consecutive patients diagnosed as having unilateral idiopathic geotropic lateral canal BPPV with a duration of symptoms of less than 2 weeks. INTERVENTIONS: Fifty-two patients (aged 32-80 yr; mean, 55.9 yr; 18 men and 34 women) were treated with CMRM that was composed of three sequential 360 degree rotations and 48 patients (aged 30-71 yr; mean, 52.4 yr; 20 men and 28 women) treated with RM that consisted of one 360-degree rotation. MAIN OUTCOME MEASURES: Resolution of vertigo on the supine roll test at 48 hours after initial maneuver and the number of maneuvers required for final resolution of vertigo were main outcome measures to assess the efficacy of treatment. RESULTS: On the supine roll test at 48-hour follow-up after initial maneuver, 44 (84.6%) of 52 CMRM-treated patients and 23 (54.2%) of 48 RM-treated patients had resolution of vertigo (p < 0.01). All patients obtained final resolution of vertigo with a maximum of five maneuvers in each group, but the CMRM group had less mean number of maneuvers required for final resolution of vertigo compared with the RM group (1.23 +/- 0.39 versus 1.63 +/- 0.68, p < 0.05). No significant adverse effects and complications occurred aside from two patients with conversion into posterior canal BPPV in each treatment. CONCLUSION: The CMRM consisting of three sequential 360-degree rotations for geotropic lateral canal BPPV has a higher initial success rate compared with the conventional RM consisting of one 360-degree rotation. PMID- 26134940 TI - AGA Section. AGA Hepatitis B Virus Reactivation Guideline: Patient Summary. PMID- 26134941 TI - AGA Clinical Practice Guidelines: Robust, Evidence-Based Tools for Guiding Clinical Care Decisions. PMID- 26134942 TI - AGA Section. Managing Pancreatic Cysts: A Patient Guide. PMID- 26134943 TI - Hydrogen Exchange Mass Spectrometry of Proteins at Langmuir Monolayers. AB - Hydrogen exchange (HX) mass spectrometry (MS) is valuable for providing conformational information for proteins/peptides that are very difficult to analyze with other methods such as peripheral membrane proteins and peptides that interact with membranes. We developed a new type of HX MS measurement that integrates Langmuir monolayers. A lipid monolayer was generated, a peptide or protein associated with it, and then the monolayer-associated peptide or protein was exposed to deuterium. The deuterated species was recovered from the monolayer, digested, and deuterium incorporation monitored by MS. Test peptides showed that deuterium recovery in an optimized protocol was equivalent to deuterium recovery in conventional solution HX MS. The reproducibility of the measurements was high, despite the requirement of generating a new monolayer for each deuterium labeling time. We validated that known conformational changes in the presence of a monolayer/membrane could be observed with the peptide melittin and the myristoylated protein Arf-1. Results in an accompanying paper show that the method can reveal details of conformational changes in a protein (HIV-1 Nef), which adopts a different conformation, depending on whether or not it is able to insert into the lipid layer. Overall, the HX MS Langmuir monolayer method provided new and meaningful conformational information for proteins that associate with lipid layers. The combination of HX MS results with neutron or X ray reflection of the same proteins in Langmuir monolayers can be more informative than the isolated use of either method. PMID- 26134944 TI - Dual mTOR Inhibition Is Required to Prevent TGF-beta-Mediated Fibrosis: Implications for Scleroderma. PMID- 26134945 TI - Decreased Expression of Caveolin-1 Contributes to the Pathogenesis of Psoriasiform Dermatitis in Mice. AB - Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal keratinocyte development, in which T helper type 17 cells and signal transducer and activator of transcription 3 (STAT3) activation have pivotal roles. Moreover, caveolin-1 (CAV-1) has been implicated in the regulation of signal transduction, and aberrant CAV-1 expression is involved in a variety of diseases. However, whether CAV-1 is involved in psoriasis is unknown. Here we examined CAV-1 expression in the psoriatic epidermis and investigated its role in the pathogenesis of psoriasis. CAV-1 was markedly reduced in lesional epidermis of psoriasis patients. CAV1 silencing in keratinocytes in vitro revealed significant activation of STAT3, leading to increased expression of keratin 16 and several cytokine/chemokines, such as IL-6, C-X-C chemokine ligand 8 (CXCL8), CXCL9, and C-C chemokine ligand 20. In addition, psoriasis-related cytokines, including tumor necrosis factor-alpha (TNF-alpha), decreased CAV-1 expression in keratinocytes. Finally, administration of CAV-1 scaffolding domain peptide in a murine model of psoriasis-like skin inflammation induced by imiquimod improved the skin phenotype and reduced epidermal thickness and infiltrating cell counts. Furthermore, expression of TNF-alpha, IL-17A, and IL-23 was significantly suppressed by this treatment. Collectively, our study indicated that CAV-1 participates in the pathogenesis of psoriasis by regulating the STAT3 pathway and cytokine networks. PMID- 26134946 TI - Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance of Tension in the Collagen Matrix. AB - Cell-mediated remodeling and wound closure are critical for efficient wound healing, but the contribution of actin-binding proteins to contraction of the extracellular matrix is not defined. We examined the role of filamin A (FLNa), an actin filament cross-linking protein, in wound contraction and maintenance of matrix tension. Conditional deletion of FLNa in fibroblasts in mice was associated with ~4 day delay of full-thickness skin wound contraction compared with wild-type (WT) mice. We modeled the healing wound matrix using cultured fibroblasts plated on grid-supported collagen gels that create lateral boundaries, which are analogues to wound margins. In contrast to WT cells, FLNa knockdown (KD) cells could not completely maintain tension when matrix compaction was resisted by boundaries, which manifested as relaxed matrix tension. Similarly, WT cells on cross-linked collagen, which requires higher levels of sustained tension, exhibited approximately fivefold larger deformation fields and approximately twofold greater fiber alignment compared with FLNa KD cells. Maintenance of boundary-resisted tension markedly influenced the elongation of cell extensions: in WT cells, the number (~50%) and length (~300%) of cell extensions were greater than FLNa KD cells. We conclude that FLNa is required for wound contraction, in part by enabling elastic deformation and maintenance of tension in the matrix. PMID- 26134947 TI - Sensitization of Melanoma Cells for Death Ligand TRAIL Is Based on Cell Cycle Arrest, ROS Production, and Activation of Proapoptotic Bcl-2 Proteins. AB - The death ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) represents a promising strategy for melanoma due to significant expression of TRAIL receptor 1 in melanoma metastases and high TRAIL sensitivity through this receptor. However, prevalent and inducible resistance are limiting its clinical use. In previous work, we and others have described multiple strategies leading to TRAIL sensitization; however, the common principles of these strategies remained elusive. Here, we demonstrate in melanoma cell lines (TRAIL-sensitive, TRAIL-resistant, and TRAIL-selected cells with acquired resistance) that cell cycle arrest clearly correlates with enhanced TRAIL sensitivity. Cell cycle arrest was induced by high cell confluence, serum starvation, or cyclin-dependent kinase (CDK) 4/6 inhibition. Addressing the signaling pathways revealed disruption of mitochondrial membrane potential and production of reactive oxygen species (ROS) in response to antiproliferative conditions alone. Activation of the proapoptotic Bcl-2 protein Bax and inhibition of apoptosis by Bcl-2 overexpression or by the antioxidant N-acetyl cysteine underlined the critical involvement of mitochondrial apoptosis pathways and of ROS, respectively. Most pronounced was the upregulation of small proapoptotic Bcl-2 proteins (Puma and Bcl-xS). These data provide a general understanding on TRAIL sensitization as well as an alternative view on CDK inhibitors and may suggest selective targeting of melanoma cells by cell cycle inhibition and TRAIL. PMID- 26134948 TI - IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin Resistant Staphylococcus aureus. AB - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major nosocomial pathogen that is widespread in both health-care facilities and in the community at large, as a result of direct host-to-host transmission. Several virulence factors are associated with pathogen transmission to naive hosts. Immunodominant surface antigen B (IsaB) is a virulence factor that helps Staphylococcus aureus to evade the host defense system. However, the mechanism of IsaB on host transmissibility remains unclear. We found that IsaB expression was elevated in transmissible MRSA. Wild-type isaB strains inhibited autophagic flux to promote bacterial survival and elicit inflammation in THP-1 cells and mouse skin. MRSA isolates with increased IsaB expression showed decreased autophagic flux, and the MRSA isolate with the lowest IsaB expression showed increased autophagic flux. In addition, recombinant IsaB rescued the virulence of the isaB deletion strain and increased the group A streptococcus (GAS) virulence in vivo. Together, these results reveal that IsaB diminishes autophagic flux, thereby allowing MRSA to evade host degradation. These findings suggest that IsaB is a suitable target for preventing or treating MRSA infection. PMID- 26134949 TI - Photoactivation of ROS Production In Situ Transiently Activates Cell Proliferation in Mouse Skin and in the Hair Follicle Stem Cell Niche Promoting Hair Growth and Wound Healing. AB - The role of reactive oxygen species (ROS) in the regulation of hair follicle (HF) cycle and skin homeostasis is poorly characterized. ROS have been traditionally linked to human disease and aging, but recent findings suggest that they can also have beneficial physiological functions in vivo in mammals. To test this hypothesis, we transiently switched on in situ ROS production in mouse skin. This process activated cell proliferation in the tissue and, interestingly, in the bulge region of the HF, a major reservoir of epidermal stem cells, promoting hair growth, as well as stimulating tissue repair after severe burn injury. We further show that these effects were associated with a transient Src kinase phosphorylation at Tyr416 and with a strong transcriptional activation of the prolactin family 2 subfamily c of growth factors. Our results point to potentially relevant modes of skin homeostasis regulation and demonstrate that a local and transient ROS production can regulate stem cell and tissue function in the whole organism. PMID- 26134951 TI - Impact of P/In flux ratio and epilayer thickness on faceting for nanoscale selective area growth of InP by molecular beam epitaxy. AB - The impact of the P/In flux ratio and the deposited thickness on the faceting of InP nanostructures selectively grown by molecular beam epitaxy (MBE) is reported. Homoepitaxial growth of InP is performed inside 200 nm wide stripe openings oriented either along a [110] or [1-10] azimuth in a 10 nm thick SiO2 film deposited on an InP(001) substrate. When varying the P/In flux ratio, no major shape differences are observed for [1-10]-oriented apertures. On the other hand, the InP nanostructure cross sections strongly evolve for [110]-oriented apertures for which (111)B facets are more prominent and (001) ones shrink for large P/In flux ratio values. These results show that the growth conditions allow tailoring the nanocrystal shape. They are discussed in the framework of the equilibrium crystal shape model using existing theoretical calculations of the surface energies of different low-index InP surfaces as a function of the phosphorus chemical potential, directly related to the P/In ratio. Experimental observations strongly suggest that the relative (111)A surface energy is probably smaller than the calculated value. We also discuss the evolution of the nanostructure shape with the InP-deposited thickness. PMID- 26134950 TI - Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells. AB - Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin interact with UVA radiation to generate reactive oxygen species that diminish NER capacity by causing protein damage. The replication protein A (RPA) DNA-binding protein has a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation, and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage, and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself, is likely to be an important contributor to skin cancer risk. PMID- 26134952 TI - Increased expression of Notch 1 in a rat liver transplantation model. AB - Liver transplantation is the standard treatment for end-stage liver failure; however, rejection can result in allograft failure. In order to investigate the role of Notch 1 during rejection, the present study evaluated Notch 1 expression, as well as the levels of immune reactivity, in rat liver allografts. A heterotopic liver transplantation model was established using Dark Agouti (DA) rats as donors and Lewis rats as recipients (DA/Lewis), with DA recipient rats serving as controls (DA/DA). The concentration levels of immune reactivity markers and serum Notch 1 were measured on days 3, 5, and 7. The overall survival was significantly shorter (<10 days) in the DA/Lewis group, as compared with the DA/DA group (P<0.0001). The concentration levels of serum alanine aminotransferase and total bilirubin were significantly higher 5 and 7 days following transplantation in the DA/Lewis group, as compared with the DA/DA group (P<0.001). The concentration levels of serum Notch 1 were significantly higher in the DA/Lewis group, as compared with the DA/DA group on days 3, 5, and 7 following transplantation (P<0.0001). These results indicate that the expression levels of serum Notch 1 significantly increase during liver allograft rejection, suggesting that Notch 1 is involved in the mechanism underlying liver allograft rejection. Notch 1 may serve as a marker of acute rejection in a rat liver transplantation model. PMID- 26134953 TI - An assay to probe Plasmodium falciparum growth, transmission stage formation and early gametocyte development. AB - Conversion from asexual proliferation to sexual differentiation initiates the production of the gametocyte, which is the malaria parasite stage required for human-to-mosquito transmission. This protocol describes an assay designed to probe the effect of drugs or other perturbations on asexual replication, sexual conversion and early gametocyte development in the major human malaria parasite Plasmodium falciparum. Synchronized asexually replicating parasites are induced for gametocyte production by the addition of conditioned medium, and they are then exposed to the treatment of interest during sexual commitment or at any subsequent stage of early gametocyte development. Flow cytometry is used to measure asexual proliferation and gametocyte production via DNA dye staining and the gametocyte-specific expression of a fluorescent protein, respectively. This screening approach may be used to identify and evaluate potential transmission blocking compounds and to further investigate the mechanism of sexual conversion in malaria parasites. The full protocol can be completed in 11 d. PMID- 26134954 TI - Generation and isolation of oligodendrocyte progenitor cells from human pluripotent stem cells. AB - In the CNS, oligodendrocytes act as the myelinating cells. Oligodendrocytes have been identified to be key players in several neurodegenerative disorders. This protocol describes a robust, fast and reproducible differentiation protocol to generate human oligodendrocytes from pluripotent stem cells (PSCs) using a chemically defined, growth factor-rich medium. Within 8 d, PSCs differentiate into paired box 6-positive (PAX6(+)) neural stem cells, which give rise to OLIG2(+) progenitors by day 12. Oligodendrocyte lineage transcription factor 2 positive (OLIG2(+)) cells begin to express the transcription factor NKX2.2 around day 18, followed by SRY-box 10 (SOX10) around day 40. Oligodendrocyte progenitor cells (OPCs) that are positive for the cell surface antigen recognized by the O4 antibody (O4(+)) appear around day 50 and reach, on average, 43% of the cell population after 75 d of differentiation. O4(+) OPCs can be isolated by cell sorting for myelination studies, or they can be terminally differentiated to myelin basic protein-positive (MBP(+)) oligodendrocytes. This protocol also describes an alternative strategy for markedly reducing the length and the costs of the differentiation and generating ~30% O4(+) cells after only 55 d of culture. PMID- 26134955 TI - Using the chicken embryo to assess virulence of Listeria monocytogenes and to model other microbial infections. AB - Microbial infections are a global health problem, particularly as microbes are continually developing resistance to antimicrobial treatments. An effective and reliable method for testing the virulence of different microbial pathogens is therefore a useful research tool. This protocol describes how the chicken embryo can be used as a trustworthy, inexpensive, ethically desirable and quickly accessible model to assess the virulence of the human bacterial pathogen Listeria monocytogenes, which can also be extended to other microbial pathogens. We provide a step-by-step protocol and figures and videos detailing the method, including egg handling, infection strategies, pathogenicity screening and isolation of infected organs. From the start of incubation of the fertilized eggs, the protocol takes <4 weeks to complete, with the infection part taking only 3 d. We discuss the appropriate controls to use and potential adjustments needed for adapting the protocol for other microbial pathogens. PMID- 26134957 TI - Foreword. PMID- 26134956 TI - Tuning the isoelectric point of graphene by electrochemical functionalization. AB - The ability to control the charge-potential landscape at solid-liquid interfaces is pivotal to engineer novel devices for applications in sensing, catalysis and energy conversion. The isoelectric point (pI)/point of zero charge (pzc) of graphene plays a key role in a number of physico-chemical phenomena occurring at the graphene-liquid interface. Supported by theory, we present here a methodology to identify the pI/pzc of (functionalized) graphene, which also allows for estimating the nature and extent of ion adsorption. The pI of bare graphene (as prepared, chemical vapor deposition (CVD)-grown) is found to be less than 3.3, which we can continuously modify up to 7.5 by non-covalent electrochemical attachment of aromatic amino groups, preserving the favorable electronic properties of graphene throughout. Modelling all the observed results with detailed theory, we also show that specific adsorption of ions and the substrate play only an ancillary role in our capability to tune the pI of graphene. PMID- 26134958 TI - Optical diagnosis of colorectal lesions requires technology, dedication, and knowledge of its limits. PMID- 26134959 TI - Comprehensive confocal endomicroscopy of the esophagus in vivo. AB - BACKGROUND AND STUDY AIMS: Biopsy sampling error can be a problem for the diagnosis of certain gastrointestinal tract diseases. Spectrally-encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has the potential to overcome sampling error by imaging large regions of gastrointestinal tract tissues. The aim of this study was to test a recently developed SECM endoscopic probe for comprehensively imaging large segments of the esophagus at the microscopic level in vivo. METHODS: Topical acetic acid was endoscopically applied to the esophagus of a normal living swine. The 7 mm diameter SECM endoscopic probe was transorally introduced into the esophagus over a wire. Optics within the SECM probe were helically scanned over a 5 cm length of the esophagus. Confocal microscopy data was displayed and stored in real time. RESULTS: Very large confocal microscopy images (length = 5 cm; circumference = 2.2 cm) of swine esophagus from three imaging depths, spanning a total area of 33 cm(2), were obtained in about 2 minutes. SECM images enabled the visualization of cellular morphology of the swine esophagus, including stratified squamous cell nuclei, basal cells, and collagen within the lamina propria. CONCLUSIONS: The results from this study suggest that the SECM technology can rapidly provide large, contiguous confocal microscopy images of the esophagus in vivo. When applied to human subjects, the unique comprehensive, microscopic imaging capabilities of this technology may be utilized for improving the screening and surveillance of various esophageal diseases. PMID- 26134960 TI - Risk factors for pyrexia after endoscopic submucosal dissection of gastric lesions. AB - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is widely used in the resection of gastric tumors en bloc, however, complications such as pyrexia frequently occur following the procedure. The study aim was to elucidate the incidence, clinical characteristics, and risk factors of post-ESD pyrexia. PATIENTS AND METHODS: We conducted a retrospective cohort study of 471 consecutive patients with 485 gastric lesions resected by ESD between December 2005 and 2010. Pyrexia was defined as body temperature above 37.5 degrees C, regardless of its duration. Blood tests and chest radiography were performed three times before and after ESD. Chest and abdominal computed tomography (CT) was taken on postoperative day 1. RESULTS: Post-ESD pyrexia developed in 117 patients (24.8 %), including 40 patients with pneumonia as shown by computed tomography. The pyrexia was resolved in all the patients after 1 day (median; range, 1 - 36 days). A multivariate analysis identified age (P = 0.0029) and resection diameter (P = 0.0009) as risk factors for pyrexia in patients without pneumonia, and operation time (P = 0.0025) as a risk factor for pyrexia in patients with pneumonia. CONCLUSION: The patient would be at risk for post-ESD pyrexia if a large ESD is performed in the elderly. The longer operation time would raise the risk for pneumonia-associated fever. PMID- 26134961 TI - Supratherapeutic anticoagulation at presentation is associated with reduced mortality in nonvariceal upper gastrointestinal hemorrhage. AB - INTRODUCTION: Warfarin is a widely used and easily reversible anticoagulant. Although bleeding is more likely in warfarin users, it may also be more readily treated. This retrospective observational case-control study compares the outcome of acute nonvariceal upper gastrointestinal hemorrhage in warfarin users with a supratherapeutic international normalized ratio (INR) and outcome in non - warfarin users. PATIENTS AND METHODS: Clinical and endoscopic data for patients presenting with overt upper gastrointestinal hemorrhage were collected between 23rd February 2001 and 12 October 2010. Patients with variceal hemorrhage were excluded. Warfarin users with a supratherapeutic INR (>= 3.0) at presentation (supratherapeutic anticoagulation [SA] group) were matched to a cohort with upper gastrointestinal hemorrhage not taking warfarin at presentation (control group). Patients were matched by age, sex, Rockall score, year of endoscopy, inpatient or outpatient status, and the presence of disseminated cancer at presentation. The incidence rates of major outcomes in the two groups were compared. RESULTS: A total of 128 patients (SA group) were matched to 135 control patients. The SA group patients were less likely to die within 30 days (6.25 % vs. 15.5 %, odds ratio = 0.36, P = 0.028 by Test for Equality of Proportions). There was a trend toward more surgery in the control group (5 % vs. 2 %), and rates of blood transfusion (77 % vs. 70 %) were similar in the two groups. CONCLUSION: In patients presenting with nonvariceal upper gastrointestinal hemorrhage, a supratherapeutic INR at presentation due to warfarin use is associated with reduced mortality. PMID- 26134962 TI - A pilot study of EUS-guided fiducial insertion for the multidisciplinary management of gastric cancer. AB - BACKGROUND AND STUDY AIMS: The 5-year survival rates for gastric cancer remain poor despite evolving therapies, and fiducial insertion via endoscopic ultrasound (EUS) is novel within this setting. We aimed to assess the feasibility of fiducial insertion for response assessment and anatomic localization in patients with gastric cancer. PATIENTS AND METHODS: A prospective phase II feasibility study was undertaken at Austin Health (Victoria, Australia) from February 2011 to November 2012. Consecutive adult patients were enrolled who had primary adenocarcinoma of the stomach with American Joint Committee on Cancer stage T1 - 3,N0 - 1,M0 - 1a and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. In addition, the patients were medically suitable for gastrectomy and chemotherapy/chemoradiotherapy. Gold fiducial markers were inserted under EUS guidance into the margins of the gastric cancer primary. The main outcome was successful insertion of the fiducial without complications for response assessment and anatomic localization. RESULTS: A total of 15 fiducials were successfully inserted into 7 (88 %) of 8 patients. No immediate or delayed complications were noted. One patient proceeded to image-guided radiotherapy through the use of fiducials and is disease free at 12 months. Fiducials were used to assess treatment response in all patients who underwent computed tomographic imaging after insertion. Follow-up computed tomography with fiducial placement improved anatomic localization and estimation of the gastric cancer primary size in 3 (60 %) of 5 patients. CONCLUSIONS: Within the limitations of our small study cohort, fiducials were placed in gastric cancers under EUS guidance without complications, and placement was successful in the majority of our patients. Although potential benefits exist, there remain substantial limitations to the generalization of this technique across our patient population. PMID- 26134963 TI - Prospective, randomized, comparative study of delineation capability of radial scanning and curved linear array endoscopic ultrasound for the pancreaticobiliary region. AB - BACKGROUND AND STUDY AIMS: There are two types of endoscopic ultrasound (EUS) endoscope, the radial scanning (RS) and the curved linear array (CL). The type of EUS endoscope used at a first intent depends on local expertise, local habits and sometimes on how the examination is reimbursed. In Japan, RS is mainly used for observation, whereas CL is primarily used for histopathological diagnosis and treatment. We compared the imaging capabilities of RS and CL in evaluating the pancreaticobiliary region, a study which has not been performed previously. PATIENTS AND METHODS: This prospective and randomized trial included 200 patients undergoing endoscopic ultrasonography of the pancreaticobiliary region by RS (n = 99) or CL (n = 101). The primary end point was the basal imaging capability of each technique. Eleven pancreaticobiliary areas were assessed and scored (range, 0 - 2). Endoscopists evaluated each criterion, and a transcriber recorded the decisions in real time. RESULTS: The mean imaging scores in the RS and CL groups were 18.39 and 19.62, respectively (significantly higher in CL, 95 %CI: 0.82 - 1.64). Although no significant difference in imaging capability for the pancreatic head, body, or tail was observed between CL and RS, the imaging capability of CL for the pancreatic head - body transition region was superior to that of RS. Although no significant difference in imaging capability for the middle and inferior bile duct or the cystic duct was observed between CL and RS, the imaging capability of RS for the major duodenal papilla and gallbladder was superior to that of CL. For the area from the hepatic portal region to the superior bile duct, the imaging capability of CL was superior. In the delineation of the branch area of the celiac and superior mesenteric arteries, CL was also superior to RS. CONCLUSIONS: The non-inferiority of the overall imaging capability of CL to that of RS was demonstrated. CL was superior in the delineation of the pancreatic head - body transition region, the area from the hepatic portal region to the superior bile duct, and the vascular bifurcation, whereas RS was superior in the delineation of the major duodenal papilla and gallbladder. Thus, for detailed evaluations of specific areas, the choice of scope should probably be considered. PMID- 26134964 TI - Molecular features of colorectal polyps presenting Kudo's type II mucosal crypt pattern: are they based on the same mechanism of tumorigenesis? AB - BACKGROUND AND STUDY AIMS: The molecular features of serrated polyps (SPs) with hyperplastic crypt pattern, also called Kudo's type II observed by chromoendoscopy, were evaluated. METHODS: The clinicopathological and molecular features of 114 SPs with a hyperplastic pit pattern detected under chromoendoscopy (five dysplastic SPs, 63 sessile serrated adenoma/polyps (SSA/Ps), 36 microvesicular hyperplastic polyps (MVHPs), and 10 goblet cell-rich hyperplastic polyps (GCHPs)) were examined. The frequency of KRAS and BRAF mutations and CpG island methylator phenotype (CIMP) were investigated. RESULTS: Dysplastic SPs and SSA/Ps were frequently located in the proximal colon compared to others (SSA/Ps vs. MVHPs or GCHPs, P < 0.0001). No significant difference was found in the frequency of BRAF mutation among SPs apart from GCHP (60 % for dysplastic SPs, 44 % for SSA/Ps, 47 % for MVHPs, and 0 % for GCHPs). The frequency of CIMP was higher in dysplastic SPs or SSA/Ps than in MVHPs or GCHPs (60 % for dysplastic SPs, 56 % for SSA/Ps, 32 % for MVHPs, and 10 % for GCHPs) (SSA/Ps vs. GCHP, P = 0.0068). When serrated neoplasias (SNs) and MVHPs were classified into proximal and distal lesions, the frequency of CIMP was significantly higher in the proximal compared to the distal SNs (64 % vs. 11 %, P = 0.0032). Finally, multivariate analysis showed that proximal location and BRAF mutation were significantly associated with an increased risk of CIMP. CONCLUSIONS: Distinct molecular features were observed between proximal and distal SPs with hyperplastic crypt pattern. Proximal MVHPs may develop more frequently through SSA/Ps to CIMP cancers than distal MVHPs. PMID- 26134965 TI - In vivo histopathological assessment of the muscularis propria in achalasia by using endocytoscopy (with video). AB - BACKGROUND: The histopathology of the muscularis propria (MP) is unknown in patients with achalasia. Endocytoscopy (EC) was developed as an ultra-high magnification endoscopy, and the submucosal tunnel created during peroral endoscopic myotomy (POEM) not only provides access to the MP but also enables subsequent endoscopic assessment of the MP. PATIENTS AND METHODS: In seven patients with achalasia (mean +/- SD; 35 +/- 18.1 years; men:women, 4:3) who underwent POEM (myotomy length: 12 +/- 2.2 cm), subsequent EC examination was performed from the mid-esophagus to the gastric side. EC images were compared to the results of histopathologic examination (two biopsies from the mid-esophagus and lower esophageal sphincter), which was the standard. RESULTS: In all patients, favorable EC images were obtained, and spindle-shaped smooth muscle cells were detected. In our series, we observed no notable features such as atrophy or hypertrophy of smooth muscle cells. In addition, the EC assessment was consistent with the results of biopsy. No complications were encountered during any of the procedures. CONCLUSION: In a clinical setting, real-time assessment of the MP using EC is feasible. This technique may play an important role in determining the pathology of achalasia and other diseases that affect gastrointestinal function. PMID- 26134966 TI - Analysis of a grading system to assess the quality of small-bowel preparation for capsule endoscopy: in search of the Holy Grail. AB - BACKGROUND: The diagnostic yield of capsule endoscopy is vulnerable to inadequate visualization related to residual bile or chyme remaining in the lumen despite intestinal lavage. It has been challenging to determine the optimal lavage preparation of the bowel and patient diet before capsule endoscopy, as well as the timing of the procedure, because no well-accepted, validated grading system for assessing the quality of intestinal lavage before capsule endoscopy is available. There remains no consensus on the reliability of qualitative, quantitative, or computer-derived assessments of the quality of preparation for capsule endoscopy. This study evaluates intra-observer and interobserver agreement for a previously validated scale. MATERIALS AND METHODS: The digital images of 34 patients who underwent capsule endoscopy were independently reviewed by two blinded physicians according to a previously validated grading scale. One of the physicians reviewed and graded the patients a second time. The quality of the bowel luminal preparation was assessed with a qualitative parameter (fluid transparency) and a more quantitative parameter (mucosal invisibility) for each of three small-intestinal segments, and an overall small-bowel score for each parameter was assigned as well. A weighted kappa coefficient was used to calculate intra-observer (observer 1A and 1B) and interobserver (observer 1A and observer 2) agreement. A kappa value of 0.60 or more suggests strong agreement, 0.40 to 0.60 moderate agreement, and less than 0.40 poor agreement. RESULTS: The intra-observer weighted kappa index for both fluid transparency and mucosal visibility was 0.52, which is consistent with moderate agreement. The interobserver weighted kappa indices for fluid transparency and mucosal invisibility were 0.29 and 0.42, respectively, demonstrating suboptimal interobserver agreement. The individual segment interobserver kappa indices were better for mucosal visibility (0.52, 0.39, and 0.47 for small-bowel segments 1, 2, and 3, respectively) than for fluid transparency (0.18, 0.38, and 0.31). CONCLUSIONS: The proposed grading scale for assessing the quality of preparation for capsule endoscopy has inadequate interobserver and intra-observer agreement. Capsule endoscopy preparation grading scales that focus more on quantitative than on qualitative assessment may demonstrate more reliable performance characteristics. Optimizing the quality of preparation and diagnostic yield of capsule endoscopy will first require the development of a well-validated grading scale. PMID- 26134967 TI - Pseudomelanosis of the stomach and duodenum: an uncommon endoscopic finding. AB - A woman (70-years) with a history of iron deficiency anemia and chronic kidney disease presented with two weeks of abdominal pain. Upper endoscopy demonstrated the gastric and duodenal mucosa was black and speckled consistent with diagnosis of pseudomelanosis. Biopsies showed pigment-laden macrophages in the lamina propria, which stained positive for iron and Masson-Fontana trichrome stain consistent with a "melanin-like" pigment. Although an uncommon endoscopic finding, this pigment has been associated with the use of certain medications, antihypertensives and iron supplements, and systemic illnesses, including hypertension, chronic kidney disease, gastric hemorrhage, and diabetes mellitus. PMID- 26134968 TI - Polyethylene glycol submucosal irrigation: a novel approach to improve visibility during endoscopic submucosal dissection. AB - In order to expand the availability of endoscopic submucosal dissection (ESD), measures to facilitate the procedure are necessary. When bleeding occurs, the examiner's field of vision is critically impaired, and ESD becomes less efficient and more hazardous because of the presence of submucosal hematoma and covered blood clot. We propose the use of polyethylene glycol (PEG) irrigation as a simple and effective measure to improve visibility during submucosal dissection, particularly when bleeding occurs. PEG irrigation facilitates further dissection by allowing a better recognition of the submucosal fibers and muscularis propria layer. PMID- 26134969 TI - Detection of Cardiac Toxicity Due to Cancer Treatment: Role of Cardiac MRI. AB - OPINION STATEMENT: Common cancer treatments including anthracycline-based chemotherapy, tyrosine kinase inhibitors, and thoracic radiation therapy can result in short- and long-term cardiovascular complications with a significant impact on morbidity and mortality. Anthracycline-based chemotherapy and tyrosine kinase inhibitors are associated with left ventricular systolic dysfunction and heart failure. Radiation therapy is associated with restrictive cardiomyopathy, coronary artery disease, as well as pericardial and valvular disease. The current standard surveillance of oncology patients for cardiotoxicity involves echocardiography, radionuclide cardiac blood pool imaging, and cardiac magnetic resonance (CMR) imaging. CMR can be used to evaluate ventricular structure and function, which is important for management decisions to prevent further cardiac injury. In patients for whom standard surveillance imaging demonstrates a drop in systolic function with or without symptoms, the use of CMR is an appropriate next step for further evaluation due to the accuracy and reproducibility of measurements of function and volumes combined with the additive information provided by tissue characterization through imaging of myocardial edema and myocardial fibrosis, although the clinical applications of these latter are as yet unclear. Overall, detection of early cardiotoxicity is important since therapeutic response is improved with prompt initiation of medical treatment. PMID- 26134970 TI - GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines. AB - Mechanisms leading to inhibitory effects of an anti-GD2 ganglioside (GD2) 14G2a mouse monoclonal antibody (mAb) and PI3K/Akt/mTOR pathway inhibitors on human neuroblastoma cell survival were studied in vitro. We have recently shown on IMR 32, CHP-134, and LA-N-1 neuroblastoma cells that targeting GD2 with the mAb decreases cell viability of the cell lines. In this study we used cytotoxicity assays, proteomic arrays and immunoblotting to evaluate the response of the three cell lines to the anti-GD2 14G2a mAb and specific PI3K/Akt/mTOR pathway inhibitors. We show here that the mAb modulates intracellular signal transduction through changes in several kinases and their substrates phosphorylation. More detailed analysis of the PI3K/Akt/mTOR pathway showed significant decrease in activity of Akt, mTOR, p70 S6 and 4E-BP1 proteins and transient increase in PTEN (a suppressor of the pathway), leading to inhibition of the signaling network responsible for stimulation of translation and proliferation. Additionally, combining the GD2-specific 14G2a mAb with an Akt inhibitor (perifosine), dual mTOR/PI3K inhibitors (BEZ-235 and SAR245409), and a pan-PI3K inhibitor (LY294002) was shown to enhance cytotoxic effects against IMR-32, CHP-134 and LA-N-1 cells. Our study extends knowledge on mechanisms of action of the 14G2a mAb on the neuroblastoma cells. Also, it stresses the need for further delineation of molecular signal orchestration aimed at more reasonable selection of drugs to target key cellular pathways in quest for better cure for neuroblastoma patients. PMID- 26134971 TI - Strain echocardiography identifies impaired longitudinal systolic function in patients with septic shock and preserved ejection fraction. AB - BACKGROUND: Myocardial dysfunction is recognized in sepsis. We hypothesized that mechanical left (LV) and right (RV) ventricular function analysed using 2 dimensional speckle-tracking echocardiography in a cohort of early severe sepsis or septic shock patients, would be different to that of a group of critically ill, non-septic patients. METHODS: Critically ill adult patients with early, severe sepsis/septic shock (n = 48) and major trauma patients with no sepsis (n = 24) were included retrospectively, as well as healthy controls (n = 16). Standard echocardiographic examinations, including right (RV) left (LV) volumes and mitral, aortic and pulmonary vein Doppler flow profiles, were retrospectively identified and the studies were then reanalysed for assessment of myocardial strain using speckle-tracking echocardiography. Endocardial tracing of the LV was performed in apical four-chamber (4-Ch), two-chamber (2-Ch), apical long-axis (3 Ch) and apical views of RV determining the longitudinal LV and RV free wall strain in each subject. RESULTS: In septic patients, heart rate was significantly higher (p = 0.009) and systolic (p < 0.001) and mean arterial pressures (p < 0.001), as well as systemic vascular resistance (p < 0.001) were significantly lower when compared to the non-septic trauma group. Ninety-three per cent of the septic patients and 50% of the trauma patients were treated with norepinephrine (p < 0.001). LV ejection fraction (LVEF) was lower in the septic patients (p = 0.019). In septic patients with preserved LVEF (>50%, n = 34), seventeen patients (50%) had a depressed LV global longitudinal function, defined as a LV global strain > -15%, compared to two patients (8.7%) in the non-septic group (p = 0.0014). In septic patients with preserved LVEF, LV global and RV free wall strain were 14% (p = 0.014) and 17% lower (p = 0.008), respectively, compared to the non-septic group with preserved LVEF. There were no significant differences between groups with respect to LV end-diastolic or end-systolic volumes, stroke volume, or cardiac output. There were no signs of diastolic dysfunction from the mitral or pulmonary vein Doppler profiles in the septic patients. CONCLUSIONS: LV and RV systolic function is impaired in critically ill patients with early septic shock and preserved LVEF, as detected by Speckle-tracking 2D echocardiography. Strain imaging may be useful in the early detection of myocardial dysfunction in sepsis. PMID- 26134972 TI - Tartary buckwheat on nitric oxide-induced inflammation in RAW264.7 macrophage cells. AB - We investigated the effects of tartary buckwheat (TB, Fagopyrum tataricum) on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)- and interferon (IFN)-gamma-stimulated RAW264.7 cells. We evaluated the anti inflammatory effects of TB against the LPS- and IFN-gamma-stimulated inflammatory response in RAW264.7 macrophage cells. We fractionated TB to obtain 4 fractions including the n-hexane, methylene chloride, ethyl acetate (EtOAc), and n-butanol fractions. In addition, rutin was isolated and identified from the EtOAc fraction. The 4 fractions and rutin effectively inhibited the production of reactive oxygen species, nitric oxide (NO), and interleukin-6. In addition, the mRNA expression levels of pro-inflammatory factors including nuclear factor kappa B, cyclooxygenase-2, and inducible NO synthase were down-regulated in LPS- and IFN-gamma-stimulated RAW264.7 cells following treatment with the 4 fractions and rutin. The present study suggests that TB could induce anti-inflammation by regulating the expression of inflammatory mediators. PMID- 26134973 TI - Evaluation of variability in target volume delineation for newly diagnosed glioblastoma: a multi-institutional study from the Korean Radiation Oncology Group. AB - BACKGROUND: This study aimed for a collaborative evaluation of variability in the target volumes for glioblastoma, determined and contoured by different radiotherapy (RT) facilities in Korea. METHODS: Fifteen panels of radiation oncologists from independent institutions contoured the gross target volumes (GTVs) and clinical target volumes (CTVs) for 3-dimensional conformal RT or intensity-modulated RT on each simulation CT images, after scrutinizing the enhanced T1-weighted and T2-weighted-fluid-attenuated inversion recovery MR images of 9 different cases of glioblastoma. Degrees of contouring agreement were analyzed by the kappa statistics. Using the algorithm of simultaneous truth and performance level estimation (STAPLE), GTVSTAPLE and CTVSTAPLE contours were derived. RESULTS: Contour agreement was moderate (mean kappa 0.58) among the GTVs and was substantial (mean kappa 0.65) among the CTVs. However, each panels' GTVs and modification of CTVs regarding anatomical structures varied. Three-fourth of contoured panels' CTVs encompassed the peritumoral areas of T2-high signal intensity (T2-HSI). Nine of nine GTVSTAPLE encompased the surgical cavity and the T1-enhanced lesions. Eight of nine CTVSTAPLE encompassed the peritumoral T2-HSI area. The median MARGIN90 and the median MARGIN95 were 1.4 cm and 1.5 cm, respectively. CONCLUSIONS: Moderate to substantial agreement existed in target volumes for 3-dimensional or intensity-modulated RT determined by radiation oncologists in Korea. According to the estimated consensus contours, the initial CTV encompassed the GTV with margin less than 2.0 cm and the whole peritumoral areas of T2-HSI. The findings of our study propose the need for further studies and modified guidelines. PMID- 26134974 TI - Systematic characterization of the peroxidase gene family provides new insights into fungal pathogenicity in Magnaporthe oryzae. AB - Fungal pathogens have evolved antioxidant defense against reactive oxygen species produced as a part of host innate immunity. Recent studies proposed peroxidases as components of antioxidant defense system. However, the role of fungal peroxidases during interaction with host plants has not been explored at the genomic level. Here, we systematically identified peroxidase genes and analyzed their impact on fungal pathogenesis in a model plant pathogenic fungus, Magnaporthe oryzae. Phylogeny reconstruction placed 27 putative peroxidase genes into 15 clades. Expression profiles showed that majority of them are responsive to in planta condition and in vitro H2O2. Our analysis of individual deletion mutants for seven selected genes including MoPRX1 revealed that these genes contribute to fungal development and/or pathogenesis. We identified significant and positive correlations among sensitivity to H2O2, peroxidase activity and fungal pathogenicity. In-depth analysis of MoPRX1 demonstrated that it is a functional ortholog of thioredoxin peroxidase in Saccharomyces cerevisiae and is required for detoxification of the oxidative burst within host cells. Transcriptional profiling of other peroxidases in DeltaMoprx1 suggested interwoven nature of the peroxidase-mediated antioxidant defense system. The results from this study provide insight into the infection strategy built on evolutionarily conserved peroxidases in the rice blast fungus. PMID- 26134975 TI - Exploring resilience in rural GP registrars--implications for training. AB - BACKGROUND: Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care providers. This study sought to explore GP registrars' perceptions of their resilience and strategies they used to maintain resilience in rural general practice. METHODS: In this qualitative interpretive research, semi-structured interviews were recorded, transcribed and analysed using an inductive approach. Initial coding resulted in a coding framework which was refined using constant comparison and negative case analysis. Authors developed consensus around the final conceptual model. Eighteen GP registrars from: Australian College of Rural and Remote Medicine Independent Pathway, and three GP regional training programs with rural training posts. RESULTS: Six main themes emerged from the data. Firstly, rural GP registrars described four dichotomous tensions they faced: clinical caution versus clinical courage; flexibility versus persistence; reflective practice versus task-focused practice; and personal connections versus professional commitment. Further themes included: personal skills for balance which facilitated resilience including optimistic attitude, self-reflection and metacognition; and finally GP registrars recognised the role of their supervisors in supporting and stretching them to enhance their clinical resilience. CONCLUSION: Resilience is maintained as on a wobble board by balancing professional tensions within acceptable limits. These limits are unique to each individual, and may be expanded through personal growth and professional development as part of rural general practice training. PMID- 26134976 TI - Diachronic Change within the Still Bay at Blombos Cave, South Africa. AB - Characteristically shaped bifacial points are stone artefacts with which the Middle Stone Age Still Bay techno-complex in Southern Africa is identified. Traditional approaches such as chaine operatoire and two-dimensional metrics in combination with attribute analyses have been used to analyse variability within Still Bay point assemblages. Here we develop a protocol to extract and analyse high resolution 3-dimensional geometric morphometric information about Still Bay point morphology. We also investigate ways in which the independent variables of time, raw-material and tool size may be driving patterns of shape variation in the Blombos Cave point assemblage. We demonstrate that at a single, stratified Still Bay site points undergo significant modal changes in tool morphology and standardization. Our results caution against (1) treatment of the Still Bay as a static technological entity and (2) drawing demographic inferences stemming from grouping Still Bay point collections within the same cultural label. PMID- 26134977 TI - Neurodevelopmental LincRNA Microsyteny Conservation and Mammalian Brain Size Evolution. AB - The mammalian neocortex has undergone repeated selection for increases and decreases in size and complexity, often over relatively short evolutionary time. But because probing developmental mechanisms across many species is experimentally unfeasible, it is unknown whether convergent morphologies in distantly related species are regulated by conserved developmental programs. In this work, we have taken advantage of the abundance of available mammalian genomes to find evidence of selection on genomic regions putatively regulating neurogenesis in large- versus small-brained species. Using published fetal human RNA-seq data, we show that the gene-neighborhood (i.e., microsynteny) of long intergenic non-coding RNAs (lincRNAs) implicated in cortical development is differentially conserved in large-brained species, lending support to the hypothesis that lincRNAs regulating neurogenesis are selectively lost in small brained species. We provide evidence that this is not a phenomenon attributable to lincRNA expressed in all tissue types and is therefore likely to represent an adaptive function in the evolution of neurogenesis. A strong correlation between transcription factor-adjacency and lincRNA sequence conservation reinforces this conclusion. PMID- 26134978 TI - Molecular phylogenetics of the species-rich angiosperm genus Goniothalamus (Annonaceae) inferred from nine chloroplast DNA regions: Synapomorphies and putative correlated evolutionary changes in fruit and seed morphology. AB - A phylogenetic study of the genus Goniothalamus (Annonaceae) is presented using maximum parsimony, maximum likelihood and Bayesian approaches, with 65 species sampled (48.5% of the genus) based on sequences of nine chloroplast DNA regions (11,214 aligned positions). The resultant phylogeny clearly indicates that Goniothalamus is monophyletic. Preliminary research initially focused on identifying synapomorphies and estimating the phylogenetic signal of selected morphological characters based on parsimony and likelihood ancestral character state reconstructions. This prescreening of characters enabled 40 to be selected for further study, and of these 15 are shown here to demonstrate significant phylogenetic signal and to provide clear synapomorphies for several infrageneric clades. Although floral structure in Goniothalamus is comparatively uniform, suggesting a common basic pattern of pollination ecology, fruit and seed morphology in the genus is very diverse and is presumably associated with different patterns of frugivory. The present study assesses correlations amongst fruit and seed characters which are putatively of functional importance with regard to frugivory and dispersal. One-way phylogenetic ANOVA indicates significant phylogenetically independent correlation between the following fruit and seed characters: fruits borne on older branches and/or on the main trunk have larger monocarps than fruits borne on young branches; and monocarps that contain seeds with a hairy testa are larger than those with glabrous seeds. We discuss fruit morphologies and potential explanations for the inferred correlations, and suggest that they may be the result of adaptation to different frugivores (birds, larger non-volant animal and primate seed dispersers, respectively). PMID- 26134979 TI - [Measuring Participation - Discussion of the Theoretical Foundations of Current Assessment Instruments]. AB - BACKGROUND: For children and adolescents social participation is a central goal of rehabilitation processes. Available measurements and evaluation tools are exposed to the problem that the theoretical foundation of the construct of participation is still unclear as well as differentiation from activity in the International Classification of Functioning, Disabilities and Health (ICF/ICF-CY) of the WHO is not made sufficiently. OBJECTIVES: The objectives of this article were (1) to illustrate the scientific discussions on the term and understanding of participation from rehabilitation science perspectives and (2) to conclude implications for practice and science. MATERIALS AND METHODS: A systematic search for participation instruments was performed in MEDLINE, CINAHL, PsycINFO, ERIC und EMBASE in August 2014. RESULTS: The available instruments are based on very different definitions of participation. The discussion about the term seems to be not yet complete. A major demand is a better operationalization of activity and participation according to the ICF/ICF-CY in the instruments. CONCLUSIONS: Before using an existing instrument, the transferability should be tested for the own context. The theoretical assumptions of participation in conjunction to ICF/ICF CY as well as the objectives of the instrument should all be clearly understood before using an existing instrument but also before the development of new instruments. PMID- 26134980 TI - 3-Dimensional Printing Rapid Prototyping for Intracranial Aneurysm Coiling: A Good Example of Precise Medicine. PMID- 26134981 TI - Posttraumatic Cervical Nerve Root Avulsion with Epidural Hematoma. AB - BACKGROUND: Cervical nerve root avulsion after trauma is a well-known occurrence. It is associated with traction injuries to the brachial plexus, commonly after high-speed motor vehicle collisions. Traumatic nerve root avulsion occurs when traction forces pull the nerve root sleeve into the intervertebral foramen with associated tearing of the meninges. The proximal nerve root retracts, and the neural foramen fills with cerebrospinal fluid and eventually forms a pseudomeningocele. Although imaging characteristics often include nerve root edema and pseudomeningoceles, there has only been one description of associated epidural hematoma in the literature. CASE DESCRIPTION: A 3-year-old girl restrained in a passenger-side rear car seat presented to the emergency department after a high-speed motor vehicle collision. The patient was found lying unconscious on the floor of the front passenger side. On arrival, she was flaccid with absent sensation in her left upper extremity, 3/5 strength in her right upper extremity, and full strength in her lower extremities. Computed tomography of the cervical spine was negative for acute fractures. Magnetic resonance imaging (MRI) of the cervical spine demonstrated a noncompressive epidural hematoma from C5-T10 and MRI brachial plexus demonstrated diffuse left cervical nerve root edema and C5-T1 nerve root avulsion with pseudomeningoceles, which were not seen on the MRI cervical spine. The patient was managed conservatively for her brachial plexus injury. CONCLUSIONS: Although pseudomeningocele formation after cervical nerve root avulsion is commonly cited, associated epidural hematomas are not well described. It is important to consider this etiology in patients with asymmetric examinations and epidural hematomas before surgical evacuation. PMID- 26134982 TI - Decoration of the layered manganese oxide birnessite with Mn(II/III) gives a new water oxidation catalyst with fifty-fold turnover number enhancement. AB - The role of the manganese average oxidation state (AOS) in water oxidation catalysis by birnessite was investigated. Low AOS samples were most active, generating O2 immediately. Samples with a relatively high AOS showed an initial induction period and decreased turnover. Mn(ii- and iii)-enriched samples gave a 10-50 fold enhancement in turnover number. PMID- 26134983 TI - Identification of possible cytotoxicity mechanism of polyethylenimine by proteomics analysis. AB - Polyethylenimine (PEI) is a polycation widely used for successful gene delivery both in vitro and in vivo experiments. However, different studies showed that PEI could be cytotoxic to transfected cells, and the mechanism of toxicity is poorly understood. Identification of PEI-interacting proteins may help in understanding the toxicity pathways. In this study, we investigated proteins that could interact with PEI in human colorectal adenocarcinoma cells (HT29). In order to identify the proteins interacting with PEI, PEI was immobilized to sepharose beads as solid matrix. The HT29 cell lysate were passed through the matrix. PEI bound proteins were isolated, and further separation was performed by two dimensional gel electrophoresis. After gel digestion, proteins were identified by matrix-assisted laser desorption/ionization-time-of-flight (TOF)/TOF mass spectrometry. Our data indicated that most of the identified PEI-interacting proteins such as shock proteins, glutathione-S-transferases, and protein disulfide isomerase are involved in apoptosis process in cells. Thus, although this is a preliminary experiment implicating the involvement of some proteins in PEI cytotoxicity, it could partly explain the mechanism of PEI cytotoxicity in cells. PMID- 26134984 TI - Interlaboratory study of novel halogenated flame retardants: INTERFLAB. AB - Flame retardants (FRs) have come under considerable scientific and public scrutiny over the past decade. A lack of reference materials and standardized analytical methods has resulted in questions regarding the variation of measurements from different studies. We evaluated this variation by performing an international interlaboratory study assessing analytical capabilities as well as the accuracy and precision of results for a range of flame retardants (International Flame Retardant Laboratory Study, INTERFLAB). Thirteen international research laboratories participated in a blind interlaboratory comparison of 24 FRs. Results demonstrate good precision within replicates of test mixtures from individual laboratories, but problematic accuracy for several FRs and laboratories. Large ranges in the values reported for decabromodiphenylethane (DBDPE), tris(1,3-dichloropropyl)phosphate (TDCIPP), tetrabromobisphenol-A (TBBPA), and hexabromocyclododecane (HBCD) (>50 % relative standard deviations among measured values) and large deviations from the reference values (>25 % bias in accuracy) suggest potential problems for comparability of results. DBDPE, HBCD, and TBBPA had significantly poorer accuracy and precision, suggesting that current analytical methods are not providing reliable results for these FRs. PMID- 26134985 TI - Major Sources of Organic Matter in a Complex Coral Reef Lagoon: Identification from Isotopic Signatures (delta13C and delta15N). AB - A wide investigation was conducted into the main organic matter (OM) sources supporting coral reef trophic networks in the lagoon of New Caledonia. Sampling included different reef locations (fringing, intermediate and barrier reef), different associated ecosystems (mangroves and seagrass beds) and rivers. In total, 30 taxa of macrophytes, plus pools of particulate and sedimentary OM (POM and SOM) were sampled. Isotopic signatures (C and N) of each OM sources was characterized and the composition of OM pools assessed. In addition, spatial and seasonal variations of reef OM sources were examined. Mangroves isotopic signatures were the most C-depleted (-30.17 +/- 0.41 0/00) and seagrass signatures were the most C-enriched (-4.36 +/- 0.72 0/00). Trichodesmium spp. had the most N-depleted signatures (-0.14 +/- 0.03 0/00) whereas mangroves had the most N-enriched signatures (6.47 +/- 0.41 0/00). The composition of POM and SOM varied along a coast-to-barrier reef gradient. River POM and marine POM contributed equally to coastal POM, whereas marine POM represented 90% of the POM on barrier reefs, compared to 10% river POM. The relative importance of river POM, marine POM and mangroves to the SOM pool decreased from fringing to barrier reefs. Conversely, the relative importance of seagrass, Trichodesmium spp. and macroalgae increased along this gradient. Overall, spatial fluctuations in POM and SOM were much greater than in primary producers. Seasonal fluctuations were low for all OM sources. Our results demonstrated that a large variety of OM sources sustain coral reefs, varying in their origin, composition and role and suggest that delta13C was a more useful fingerprint than delta15N in this endeavour. This study also suggested substantial OM exchanges and trophic connections between coral reefs and surrounding ecosystems. Finally, the importance of accounting for environmental characteristics at small temporal and spatial scales before drawing general patterns is highlighted. PMID- 26134986 TI - Delivery of Molecules into Human Corneal Endothelial Cells by Carbon Nanoparticles Activated by Femtosecond Laser. AB - Corneal endothelial cells (CECs) form a monolayer at the innermost face of the cornea and are the engine of corneal transparency. Nevertheless, they are a vulnerable population incapable of regeneration in humans, and their diseases are responsible for one third of corneal grafts performed worldwide. Donor corneas are stored in eye banks for security and quality controls, then delivered to surgeons. This period could allow specific interventions to modify the characteristics of CECs in order to increase their proliferative capacity, increase their resistance to apoptosis, or release immunosuppressive molecules. Delivery of molecules specifically into CECs during storage would therefore open up new therapeutic perspectives. For clinical applications, physical methods have a more favorable individual and general benefit/risk ratio than most biological vectors, but are often less efficient. The delivery of molecules into cells by carbon nanoparticles activated by femtosecond laser pulses is a promising recent technique developed on non-adherent cells. The nanoparticles are partly consummated by the reaction releasing CO and H2 gas bubbles responsible for the shockwave at the origin of cell transient permeation. Our aim was to develop an experimental setting to deliver a small molecule (calcein) into the monolayer of adherent CECs. We confirmed that increased laser fluence and time exposure increased uptake efficiency while keeping cell mortality below 5%. We optimized the area covered by the laser beam by using a motorized stage allowing homogeneous scanning of the cell culture surface using a spiral path. Calcein uptake reached median efficiency of 54.5% (range 50.3-57.3) of CECs with low mortality (0.5%, range (0.55-1.0)). After sorting by flow cytometry, CECs having uptaken calcein remained viable and presented normal morphological characteristics. Delivery of molecules into CECs by carbon nanoparticles activated by femtosecond laser could prove useful for future cell or tissue therapy. PMID- 26134987 TI - Reconstructing pre-natal and early childhood exposure to multi-class organic chemicals using teeth: Towards a retrospective temporal exposome. PMID- 26134988 TI - Administration of Bifidobacterium breve Decreases the Production of TNF-alpha in Children with Celiac Disease. AB - BACKGROUND: Increasing evidence suggests that not only genetics, but also environmental factors like gut microbiota dysbiosis play an important role in the pathogenesis of celiac disease (CD). AIM: The aim of our study was to investigate the effect of two probiotic strains Bifidobacterium breve BR03 and B. breve B632 on serum production of anti-inflammatory cytokine interleukin 10 (IL-10) and pro inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) in children with CD. METHODS: The study was a double-blinded, placebo-controlled trial that included 49 children with CD on gluten-free diet (GFD) randomized into two groups and 18 healthy children in the control group. The first group (24 children with CD) daily received B. breve BR03 and B632 (2 * 10(9) colony-forming units) and the second group (25 children with CD) received placebo for 3 months. RESULTS: TNF-alpha levels were significantly decreased in the first group after receiving B. breve for 3 months. On follow-up, 3 months after receiving probiotics, TNF alpha levels increased again. Children with CD who were on GFD for less than 1 year showed similar baseline TNF-alpha levels as children who were on GFD for more than 1 year. IL-10 levels were in all groups of patients below detection level. CONCLUSIONS: Probiotic intervention with B. breve strains has shown a positive effect on decreasing the production of pro-inflammatory cytokine TNF alpha in children with CD on GFD. PMID- 26134989 TI - How Good Is Good Enough? Lymph Node Metastasis After Endoscopic Resection of a Rectosigmoid Polyp. PMID- 26134991 TI - Metabolic Effects of Access to Sucrose Drink in Female Rats and Transmission of Some Effects to Their Offspring. AB - The aims of this study were, first, to examine the metabolic consequences for female rats of having unrestricted access to 10% sucrose solution and, second, to test for effects of this dietary intervention on their offspring. In Stage 1 females were mated following a 4-week period in which one group was given the sucrose in addition to their normal chow and a control group was given chow and water only. Sucrose was removed at parturition and the pups monitored until weaning. Despite the development of glucose intolerance in sucrose-fed mothers, no effects were detected on litter size or pup weights. In Stage 2 voluntary activity of offspring was assessed over postnatal days (PND) 51-60 and their glucose tolerance measured at PND89-94. Again no effect of maternal diet was detected. Only male offspring were used in Stage 3, which began when they were 13 weeks old. Four groups were given 10% sucrose solution for 48 days in a 2 x 2 design, in which one factor was maternal diet and the other was whether they were given 2-h access to an activity wheel on alternate days. Higher fasting glucose levels were found in offspring of sugar-fed mothers. Exercise increased insulin sensitivity in these rats but not in offspring of control mothers. Behavioural measures of memory in Stage 3 did not reveal any effects of maternal diet or exercise. Overall, this study suggested that, while providing 10% sucrose solution ad-libitum was sufficient to impair maternal metabolism, the impact of this dietary manipulation on offspring may be revealed only when the offspring's diet is similarly manipulated. PMID- 26134992 TI - Revealing microbial recognition by specific antibodies. AB - BACKGROUND: Recognition of microorganisms by antibodies is a vital component of the human immune response. However, there is currently very limited understanding of immune recognition of 50 % of the human microbiome which is made up of as yet un-culturable bacteria. We have combined the use of flow cytometry and pyrosequencing to describe the microbial composition of human samples, and its interaction with the immune system. RESULTS: We show the power of the technique in human faecal, saliva, oral biofilm and breast milk samples, labeled with fluorescent anti-IgG or anti-IgA antibodies. Using Fluorescence-Activated Cell Sorting (FACS), bacterial cells were separated depending on whether they are coated with IgA or IgG antibodies. Each bacterial population was PCR-amplified and pyrosequenced, characterizing the microorganisms which evade the immune system and those which were recognized by each immunoglobulin. CONCLUSIONS: The application of the technique to healthy and diseased individuals may unravel the contribution of the immune response to microbial infections and polymicrobial diseases. PMID- 26134993 TI - Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study. AB - BACKGROUND: Bleeding complications are common in cardiac surgery. Perioperative handling of heparin and protamine may influence the haemostasis. We hypothesized that heparin and protamine dosing based on individual titration curves would improve haemostasis in comparison to standard dosing. SUBJECTS AND METHODS: Sixty patients scheduled for first time elective coronary artery bypass grafting or valve surgery were included in a prospective randomized study. The patients were randomized to heparin and protamine dosing with Hepcon HMS Plus device or to standard weight and activated clotting time (ACT) based dosing. Blood samples were collected before and 10 minutes, 2 hours and 4 hours after cardiopulmonary bypass. Primary endpoint was endogenous thrombin potential in plasma 2 hours after surgery as assessed by calibrated automated thrombography. Secondary endpoints included total heparin and protamine doses, whole blood clot formation (thromboelastometry) and post-operative bleeding volume and transfusions. Heparin effect was assessed by measuring anti-Xa activity. RESULTS: Endogenous thrombin potential and clot formation deteriorated in both groups after surgery without statistically significant intergroup difference. There were no significant differences between the groups in total heparin and protamine doses, heparin effect, or postoperative bleeding and transfusions at any time point. Significant inverse correlations between anti-Xa activity and endogenous thrombin potential were observed 10 min (r = -0.43, p = 0.001), 2 hours (r = -0.66, p<0.001) and 4 hours after surgery (r = -0.58, p<0.001). CONCLUSION: In conclusion, the results suggest that perioperative heparin and protamine dosing based on individual titration curves does not improve haemostasis after cardiac surgery. Postoperative thrombin generation capacity correlates to residual heparin effect. TRIAL REGISTRATION: www.isrctn.com ISRCTN14201041. PMID- 26134994 TI - Dissecting cellulitis of the scalp: a retrospective study of 51 patients and review of literature. PMID- 26134995 TI - Development of a Biosensor-Based Rapid Urine Test for Detection of Urogenital Schistosomiasis. PMID- 26134996 TI - Geographic variation in volumetric breast density between screening regions in the Netherlands. AB - OBJECTIVES: Differences in breast density between populations may explain part of the variation in regional breast cancer screening performance. This study aimed to determine whether regional differences in breast density distribution are present in the Dutch screening population. METHODS: As part of the DENSE trial, mammographic density was measured using a fully-automated volumetric method. The regions in our study were based on the geographic coverage of 14 reading units representing a large part of the Netherlands. General linear models were used. RESULTS: Four hundred eighty-five thousand and twenty-one screening participants with a median age of 60 years were included (2013-2014). The proportion of women with heterogeneously or extremely dense breasts ranged from 32.5% to 45.7% between regions. Mean percent dense volume varied between 6.51% (95% confidence interval [CI]: 6.46-6.55) and 7.68% (95% CI: 7.66-7.71). Age differences could not explain the variation. Socio-economic status (SES) was positively associated with volumetric density in all analyses (low SES: 6.95% vs. high SES: 7.63%; p trend < 0.0001), whereas a potential association between urbanisation and breast density only became apparent after SES adjustment. CONCLUSION: There appears to be geographic variation in mammographic density in the Netherlands, emphasizing the importance of including breast density as parameter in the evaluation of screening performance. KEY POINTS: * Mammographic density may affect regional breast cancer screening performance. * Volumetric breast density varies across screening areas. * SES is positively associated with breast density. * Implications of volumetric breast density differences need to be studied further. PMID- 26134997 TI - Cardiac MRI assessment of right ventricular function: impact of right bundle branch block on the evaluation of cardiac performance parameters. AB - OBJECTIVES: Right ventricular (RV) function represents a prognostic marker in patients with corrected congenital heart disease. In up to 80 % of these patients, right branch bundle block (RBBB) exists and leads to asynchronous ventricular contraction. The aim of this retrospective study was to evaluate the change of RV performance parameters considering delayed RV end-systolic contraction. METHODS: RV volumes of 33 patients were assessed twice: 1) not taking account of RBBB (group I), and 2) considering RBBB (group II). According to the RV ejection fraction (EF) for both groups, RV function was classified in different categories (>50 % = normal, 40-50 % = mildly-, 30-40 % = moderately-, <30 % = severely-reduced). RESULTS: The mean time difference between maximal systolic contraction of the septum and RV free wall was 90.7 ms +/- 42.6. Consequently, RV end-systolic volume was significantly decreased in group II (p < 0.001). Accordingly, RV stroke volume and RV EF were significantly higher in group II (p < 0.001). There was also a significant change in the assessment of RV function (p < 0.02). CONCLUSIONS: RBBB induced delayed RV contraction can be detected at CMR. Ignoring the RV physiology in RBBB patients leads to a statistically significant underscoring of RV performance parameters. KEY POINTS: * Right branch bundle block leads to an asynchronous ventricular contraction * In CMR, a delayed right ventricular contraction due to RBBB can be detected * Ignoring RV physiology in RBBB patients leads to underscoring of RV performance. PMID- 26134998 TI - Information about radiation dose and risks in connection with radiological examinations: what patients would like to know. AB - OBJECTIVES: To find out patients' wishes for the content and sources of the information concerning radiological procedures. METHODS: A questionnaire providing quantitative and qualitative data was prepared. It comprised general information, dose and risks of radiation, and source of information. Two tables demonstrating different options to indicate the dose or risks were also provided. Patients could give one or many votes. Altogether, 147 patients (18-85 years) were interviewed after different radiological examinations using these devices. RESULTS: 95% (139/147) of the patients wished for dose and risk information. Symbols (78/182 votes) and verbal scale (56/182) were preferred to reveal the dose, while verbal (83/164) and numerical scale (55/164) on the risk of fatal cancer were preferred to indicate the risks. Wishes concerning the course, options and purpose of the examination were also expressed. Prescriber (3.9 on a scale 1-5), information letter (3.8) and radiographer (3.3) were the preferred sources. Patients aged 66-85 years were reluctant to choose electronic channels. CONCLUSIONS: Apart from general information, patients wish for dose and risk information in connection with radiological examinations. The majority preferred symbols to indicate dose and verbal scales to indicate risks, and the preferred source of information was the prescriber or information letter. KEY POINTS: * 95% of patients expect information on the dose and risks of radiation. * Symbols and verbal scale are preferred to indicate the dose. * Verbal and numerical scales are preferred to indicate fatal cancer risk. * Patients expect information on course, options and purpose of examination. * Prescriber, information letter and radiographer are popular sources of the overall information. PMID- 26134999 TI - In vitro artefact assessment of a new MR-compatible microwave antenna and a standard MR-compatible radiofrequency ablation electrode for tumour ablation. AB - OBJECTIVE: To evaluate and compare artefact configuration and diameters in a magnetic resonance (MR)-compatible prototype microwave (MW) applicator and a standard MR-compatible radiofrequency (RF) applicator for MR-guided tumour ablation. METHODS: Both applicators were tested in a phantom study at 1.5T with three sequences: T1-weighted three-dimensional volume interpolated breath-hold examination (VIBE), T1-weighted fast low angle shot (FLASH), T2-weighted turbo spin echo (TSE). Applicator orientation to main magnetic field (B0) and slice orientation were varied. Needle tip location error (TLE) was assessed, and artefact diameters were calculated. Influence of imaging parameters on artefacts was assessed with analysis of variance (ANOVA) and post hoc testing. RESULTS: MW applicator: the shaft artefact diameter measured 2.3 +/- 0.8 mm. Tip artefact diameter and length measured 2.2 +/- 0.8 mm and 2.4 +/- 1.3 mm, respectively. A prominent oval artefact (diameter: 16.5 +/- 1.8 mm, length: 19.1 +/- 2.5 mm) appeared close to the tip. TLE: - .3 +/- 0.6 mm. RF applicator: shaft and tip diameter measured 8.9 +/- 4.7 mm and 9.0 +/- .0 mm, respectively. TLE: -0.1 +/- 0.8 mm. Minimal artefacts were measured with RF applicator orientation parallel to B0 (P < 0.0001), whereas no such influence was found for MW applicator. For both applicators, significantly large artefacts were measured with T1 FLASH (P = 0.03). CONCLUSION: The MW applicator's artefact is satisfactory and seems useable for MR-guided ablation procedures. KEY POINTS: MW applicator's artefact appearance is independent of angulation to main magnetic field. MW applicator's prominent distal artefact may increase visibility under MR-guidance. RF and MW applicator's artefacts are precise concerning tip depiction. Largest artefact diameters are measured with T1-weighted fast low angle shot sequence. PMID- 26135000 TI - Real-time virtual sonography examination and biopsy for suspicious breast lesions identified on MRI alone. AB - OBJECTIVES: The purpose of our study was to assess whether there is a potential additional value of real-time virtual sonography (RVS) to second-look ultrasound (US) examination and biopsy for breast lesions identified on MRI alone. METHODS: A retrospective review of the records of 70 consecutive patients (78 lesions) with breast abnormalities identified on MRI alone was performed. All suspicious enhancing lesions were subsequently evaluated with second-look US. Lesions not observed on second-look US underwent RVS. Pathological findings were confirmed by subsequent percutaneous biopsy or excision. RESULTS: Of the 78 MRI-detected lesions, second-look US correlation was made in 50 (64 %), including 22 malignant and 28 benign lesions. The remaining 28 lesions (36 %) were scheduled to undergo RVS. Four lesions were not visible on the second breast MRI. The remaining 24 lesions were RVS correlated and underwent RVS-guided biopsy; these included seven malignant and 17 benign lesions. Overall, 74 of 74 (100 %) true MRI-detected lesions were confirmed by histological results without using MRI-guided breast biopsy. The cancer rate was 29 %. CONCLUSIONS: RVS can increase the sonographic detection and biopsy rate of lesions identified on breast MRI alone. KEY POINTS: * All 74 MRI-detected lesions were confirmed without using MRI-guided biopsy. * Four lesions were not visible on second breast MRI. * RVS can increase sonographic detection of lesions identified on breast MRI alone. * RVS-guided breast biopsy can be an alternative to MRI-guided biopsy. PMID- 26135001 TI - Region-specific changes in brain diffusivity in fetal isolated mild ventriculomegaly. AB - OBJECTIVES: To evaluate the impact of symmetric and asymmetric isolated mild ventriculomegaly (IMVM, atrial width 10-15 mm) on apparent diffusion coefficient (ADC) values in fetal brain areas. METHODS: Sixty-seven sequential fetal head magnetic resonance imaging scans (feMRI) of VM cases performed between 2009 and 2014 were compared to 38 normal feMRI scans matched for gestational age (controls). Ultrasound- and MRI-proven IMVM cases were divided into asymmetrical (AVM, >=2 mm difference in atrial width), symmetrical (SVM, <2 mm difference in atrial width), and asymmetrical IMVM with one normal-sized ventricle (AV1norm). RESULTS: ADC values were significantly elevated in the basal ganglia (BG) of the SVM and AV1norm groups compared to controls (p < 0.004 and p < 0.013, respectively). High diffusivity was constantly detected in the BG ipsilateral to the enlarged atria relative to the normal-sized atria in the AV1norm group (p < 0.03). Frontal lobe ADC values were significantly reduced in the AVM and SVM groups (p < 0.003 and p < 0.003 vs. controls). Temporal lobe ADC values were significantly reduced in the AVM group (p < 0.001 vs. controls). CONCLUSION: Isolated mild ventriculomegaly is associated with distinct ADC value changes in different brain regions. This phenomenon could reflect the pathophysiology associated with different IMVM patterns. KEY POINTS: Various ventriculomegaly patterns are associated with distinct diffusional changes. Frontal and temporal lobe ADC values are altered bilaterally, even in asymmetric ventriculomegaly. Basal ganglia ADC values are elevated ipsilateral to the enlarged ventricle. PMID- 26135003 TI - High Performance Photoluminescent Carbon Dots for In Vitro and In Vivo Bioimaging: Effect of Nitrogen Doping Ratios. AB - Photoluminescent carbon dots (CDs) have received ever-increasing attention in the application of optical bioimaging because of their low toxicity, tunable fluorescent properties, and ultracompact size. We report for the first time on enhanced photoluminescence (PL) performance influenced by structure effects among the various types of nitrogen doped (N-doped) PL CDs. These CDs were facilely synthesized from condensation carbonization of linear polyethylenic amine (PEA) analogues and citric acid (CA) of different ratios. Detailed structural and property studies demonstrated that either the structures or the molar ratio of PEAs altered the PL properties of the CDs. The content of conjugated pi-domains with C?N in the carbon backbone was correlated with their PL Quantum Yield (QY) (up to 69%). The hybridization between the surface/molecule state and the carbon backbone synergistically affected the chemical/physical properties. Also, long chain polyethylenic amine (PEA) molecule-doped CDs exhibit increasing photostability, but at the expense of PL efficiency, proving that the PL emission of high QY CDs arise not only from the sp(2)/sp(3) carbon core and surface passivation of CDs, but also from the molecular fluorophores integrated in the CDs. In vitro and in vivo bioimaging of these N-doped CDs showed strong photoluminescence signals. Good biocompatibility demonstrates their potential feasibility for bioimaging applications. In addition, the overall size profile of the as-prepared CDs is comparable to the average size of capillary pores in normal living tissues (~5 nm). Our study provides valuable insights into the effects of the PEA doping ratios on photoluminescence efficiency, biocompatibility, cellular uptake, and optical bioimaging of CDs. PMID- 26135002 TI - What kind of prostate cancers do we miss on multiparametric magnetic resonance imaging? AB - OBJECTIVE: To analyse the characteristics of prostate cancers (PrCa) detected following negative multiparametric magnetic resonance imaging (mpMRI). MATERIALS AND METHODS: Eight hundred and thirty patients with elevated prostate-specific antigen (mean 11.9 MUg/l) underwent mpMRI of the prostate at 1.5 Tesla with endorectal coil. The characteristics of all PrCa detected within 2 years after a negative mpMRI were analysed. Primary Gleason grade 4 or any grade 5 PrCa were considered high-grade (HG), Gleason score 3 + 4 intermediate grade (IG) and Gleason score <=3 + 3 low-grade (LG). Tumour size was considered 'small' when <1 cm on radical prostatectomy specimen or limited to <=2 cores on prostate biopsy. RESULTS: mpMRI was negative in 391 patients (47.1 %). In 124 patients (31.7 %) PrCa was detected within 2 years. Eighty-four (67.7 %) were LG, 22 (17.7 %) IG and 18 (14.5 %) HG. 119 (96.0 %) of the missed PrCa were organ-confined. The negative predictive value was 95.4 % (373/391) for HG PrCa. Among the 18 missed HG PrCa, 15 (83.3 %) were organ-confined and 12 (66.6 %) were small. CONCLUSION: The majority of missed tumours on mpMRI were low grade and organ-confined. In patients with elevated PSA and a negative mpMRI, consideration could be given to continued surveillance rather than immediate biopsy. KEY POINTS: * The majority of missed prostate cancers were low grade and organ-confined. * In patients with a negative mpMRI a biopsy may be postponed. * mpMRI had a negative predictive value of 95.4 % for high-grade prostate cancer. PMID- 26135004 TI - Effect of medium components and culture conditions in Bacillus subtilis EA-CB0575 spore production. AB - Bacillus subtilis spores have important biotechnological applications; however, achieving both, high spore cell densities and sporulation efficiencies in fermentation, is poorly reported. In this study, medium components and culture conditions were optimized with different statistical methods to increase spore production of the plant growth promoting rhizobacteria B. subtilis EA-CB0575. Key medium components were determined with Plackett-Burman (PB) design, and the optimum concentration levels of two components (glucose, MgSO4.7H2O) were optimized with a full factorial and central composite design, achieving 1.37 * 10(9) CFU/mL of spore cell density and 93.5 % of sporulation efficiency in shake flask. The optimized medium was used to determine the effect of culture conditions on spore production at bioreactor level, finding that maintaining pH control did not affect significantly spore production, while the interaction of agitation and aeration rates had a significant effect on spore cell density. The overall optimization generated a 17.2-fold increase in spore cell density (8.78 * 10(9) CFU/mL) and 1.9-fold increase in sporulation efficiency (94.2 %) compared to that of PB design. These results indicate the potential of B. subtilis EA CB0575 to produce both, high spore cell densities and sporulation efficiencies, with very low nutrient requirements and short incubation period which can represent savings of process production. PMID- 26135006 TI - Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling. AB - Osteosarcoma (OS) is the most common non-hematologic primary malignancy of bone, and multiple chemotherapeutic agents have been applied in the treatment of OS for over 40 years. Nevertheless, due to the poor prognosis of OS, it is essential to develop a novel treatment strategy. Evodiamine (EVO), a quinolone alkaloid extracted from the fruit of Evodia rutaecarpa, has been demonstrated to inhibit tumor cell proliferation. Thus, the main aim of the present study was to investigate the anti-proliferative and apoptosis-inducing effects of evodiamine (EVO) on human OS 143B cells, but also the possible mechanisms underlying these effects. The results of crystal violet staining, flow cytometry, western blot analysis and an in vivo experiment demonstrated that EVO exhibits significant inhibitory effects on cell proliferation, exhibits apoptosis-inducing effects and arrests the cell cycle in 143B cells. According to our findings of polymerase chain reaction (PCR), western blot analysis and recombinant adenoviral transfection, we confirmed that EVO upregulates both the protein and gene levels of phosphatase and tensin homolog (PTEN) in a concentration-dependent manner in 143B cells. Overexpression of PTEN reinforced the anti-proliferative effect of EVO in the 143B cells, while knockdown of PTEN upregulated PI3K/Akt signaling transduction and reversed the inhibitory effect of EVO on 143B cell proliferation. Further analysis indicated that EVO upregulated the expression of PTEN by inactivating PI3K/Akt signaling by decreasing phosphorylated Akt1/2. Based on the above results, we conclude that PTEN/PI3K/Akt signaling is involved in the inhibitory effect on human OS 143B cell proliferation by EVO. PMID- 26135008 TI - Intestinal Absorption and Metabolism of Epimedium Flavonoids in Osteoporosis Rats. AB - Herba Epimdii is a traditional Chinese medicine used to treat osteoporosis. Its main pharmacological ingredients are flavonoids. In previous studies conducted in healthy animals, we showed that epimedium flavonoids could be hydrolyzed into secondary glycosides or aglycon by intestinal flora or enzymes, thereby enhancing their absorption and antiosteoporosis activity. To study the medicine in the pathologic state, epimedium flavonoids were incubated with intestinal mucosa and feces in vitro and intestinal perfusion in situ to explore the differences in absorption and metabolism between sham and osteoporosis rats. For osteoporosis rats, the hydrolysis rates of icariin, epimedin A, epimedin B, and epimedin C incubated with intestinal flora for 1 hour were reduced by 0.19, 0.26, 0.19, and 0.14, respectively, compared with that in sham rats. Hydrolysis rates were reduced by 0.21, 0.24, 0.08, and 0.31 for icariin, epimedin A, epimedin B, and epimedin C incubated with duodenal enzymes for 1 hour and by 0.13, 0.09, 0.07, and 0.47 for icariin, epimedin A, epimedin B, and epimedin C incubated with jejunum enzymes, respectively, compared with the sham group. In addition, the apparent permeability coefficient and elimination percentage of the four epimedium flavonoids in the duodenum, jejunum, ileum, and colon decreased by 29% 44%, 32%-50%, 40%-56%, and 27%-53% compared with that in sham rats, respectively. The main metabolites of the four epimedium flavonoids were the same for the two groups after intestinal perfusion, or flora and enzyme incubation. In conclusion, the amount and activity of intestinal flora and enzymes changed in ovariectomized rats, which affected the intestinal absorption and hydrolysis of epimedium flavonoids whose structures contain 7-glucose. PMID- 26135005 TI - The innate immune response in human tuberculosis. AB - Mycobacterium tuberculosis (Mtb) infection can be cleared by the innate immune system before the initiation of an adaptive immune response. This innate protection requires a variety of robust cell autonomous responses from many different host immune cell types. However, Mtb has evolved strategies to circumvent some of these defences. In this mini-review, we discuss these host pathogen interactions with a focus on studies performed in human cells and/or supported by human genetics studies (such as genome-wide association studies). PMID- 26135009 TI - Further Characterization of the Metabolism of Desloratadine and Its Cytochrome P450 and UDP-glucuronosyltransferase Inhibition Potential: Identification of Desloratadine as a Relatively Selective UGT2B10 Inhibitor. AB - Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating antihistamine used for the treatment of seasonal allergies and hives. Previously we reported that the formation of 3-hydroxydesloratadine, the major human metabolite of desloratadine, involves three sequential reactions, namely N-glucuronidation by UGT2B10 followed by 3-hydroxylation by CYP2C8 followed by deconjugation (rapid, nonenzymatic hydrolysis of the N-glucuronide). In this study we assessed the perpetrator potential of desloratadine based on in vitro studies of its inhibitory effects on cytochrome P450 and UDP glucuronosyltransferase (UGT) enzymes in human liver microsomes (HLM). Desloratadine (10 uM) caused no inhibition (<15%) of CYP1A2, CYP2C8, CYP2C9, or CYP2C19 and weak inhibition (32-48%) of CYP2B6, CYP2D6, and CYP3A4/5. In cryopreserved human hepatocytes (CHH), which can form the CYP2C8 substrate desloratadine N-glucuronide, desloratadine did not inhibit the CYP2C8-dependent metabolism of paclitaxel or amodiaquine. Assessment of UGT inhibition identified desloratadine as a potent and relatively selective competitive inhibitor of UGT2B10 (Ki value of 1.3 MUM). Chemical inhibition of UGT enzymes in HLM demonstrated that nicotine (UGT2B10 inhibitor) but not hecogenin (UGT1A4 inhibitor) completely inhibited the conversion of desloratadine (1 uM) to 3 hydroxydesloratadine in HLM fortified with both NADPH and UDP-glucuronic acid. 3 Hydroxydesloratadine formation correlated well with levomedetomidine glucuronidation (UGT2B10 marker activity) with a panel of individual CHH (r(2) = 0.72). Overall, the results of this study confirm the role of UGT2B10 in 3 hydroxydesloratadine formation and identify desloratadine as a relatively selective in vitro inhibitor of UGT2B10. PMID- 26135010 TI - Early Fatal Cutaneous Lower Extremity Angiosarcoma Associated with Deep Venous Thrombosis in a Renal Transplant Recipient. AB - Angiosarcomas are extremely rare malignant tumors of vascular origin. We describe a 63-year-old recipient after a kidney transplant who had an angiosarcoma in the lower extremity that presented after new-onset deep venous thrombosis and was not associated with any fistula. There was rapid progression to metastasis and death. We reviewed the literature of this rare malignant tumor in kidney transplant patients. PMID- 26135011 TI - Spatial heterogeneity lowers rather than increases host-parasite specialization. AB - Abiotic environmental heterogeneity can promote the evolution of diverse resource specialists, which in turn may increase the degree of host-parasite specialization. We coevolved Pseudomonas fluorescens and lytic phage phi2 in spatially structured populations, each consisting of two interconnected subpopulations evolving in the same or different nutrient media (homogeneous and heterogeneous environments, respectively). Counter to the normal expectation, host-parasite specialization was significantly lower in heterogeneous compared with homogeneous environments. This result could not be explained by dispersal homogenizing populations, as this would have resulted in the heterogeneous treatments having levels of specialization equal to or greater than that of the homogeneous environments. We argue that selection for costly generalists is greatest when the coevolving species are exposed to diverse environmental conditions and that this can provide an explanation for our results. A simple coevolutionary model of this process suggests that this can be a general mechanism by which environmental heterogeneity can reduce rather than increase host-parasite specialization. PMID- 26135012 TI - Four-year visual outcomes after photorefractive keratectomy in pilots with low moderate myopia. AB - BACKGROUND: The photorefractive keratectomy (PRK) is approved for Air Force pilots in several nations. The occupational environments of pilots in the Air Force are unique, including extremely high altitude, low oxygen tension, high ultraviolet light exposure and high G-force load. The short-term efficacy and safety of PRK for pilots are documented. However, the study for long-term visual and refractive outcomes of PRK in pilots is limited. OBJECTIVE: To investigate the long-term visual and refractive outcomes in a 4-year follow-up period after PRK in pilots with low to moderate myopia. METHODS: Thirty-eight eyes of 20 subjects that underwent PRK and recruited to Air Force pilot were evaluated preoperatively and at 3, 6, 12, 24, and 48 months postoperatively. RESULTS: The mean patient age was 21.42+/-0.75 years. The mean preoperative manifest refraction spherical equivalent (SE) was -1.51+/-1.15 diopters (D). At 4 years postoperatively, the mean SE was -0.29+/-0.51, 89.5% of eyes achieved 20/20 or better Snellen uncorrected visual acuity, 71.1% of eyes were within +/-0.50 D of emmetropia. The refraction stabilised by 6 months and was maintained up to the 4 year follow-up stage. CONCLUSIONS: PRK for pilots with low to moderate myopia is safe and effective in the long term. High-altitude environmental stress exposure has no effect on the refractive stability after PRK. TRIAL REGISTRATION NUMBER: ROKAF-ASMC-2015-IRB-002. PMID- 26135013 TI - Measuring the precise area of peripheral retinal non-perfusion using ultra widefield imaging and its correlation with the ischaemic index. AB - OBJECTIVE: To determine the calculated, anatomically correct, area of retinal non perfusion and total area of visible retina on ultra-widefield fluorescein angiography (UWF FA) in retinal vein occlusion (RVO) and to compare the corrected measures of non-perfusion with the ischaemic index. METHODS: Uncorrected UWF FA images from 32 patients with RVO were graded manually for capillary non perfusion, which was calculated as a percentage of the total visible retina (uncorrected ischaemic index). The annotated images were converted using novel stereographic projection software to calculate precise areas of non-perfusion in mm(2), which was compared as a percentage of the total area of visible retina ('corrected non-perfusion percentage') with the ischaemic index. RESULTS: The precise areas of peripheral non-perfusion ranged from 0 mm(2) to 365.4 mm(2) (mean 95.1 mm(2)), while the mean total visible retinal area was 697.0 mm(2). The mean corrected non-perfusion percentage was similar to the uncorrected ischaemic index (13.5% vs 14.8%, p=0.239). The corrected non-perfusion percentage correlated with uncorrected ischaemic index (R=0.978, p<0.001), but the difference in non-perfusion percentage between corrected and uncorrected metrics was as high as 14.8%. CONCLUSIONS: Using stereographic projection software, lesion areas on UWF images can be calculated in anatomically correct physical units (mm(2)). Eyes with RVO show large areas of peripheral retinal non perfusion. PMID- 26135014 TI - DNA modulates solvent isotope effects in a nanopore. AB - Here we investigate the modulation of solvent isotope effects by the entry of DNA molecules into individual alpha-haemolysin nanopores. Solvent isotope effects in D2O versus H2O were enhanced (kH/kD ~ 1.6) compared to the bulk (kH/kD ~ 1.2), except when the pore was most blocked (kH/kD <= 1.1). PMID- 26135015 TI - Radiotherapy did not increase thyroid cancer risk among women with breast cancer: A nationwide population-based cohort study. AB - The aim of this study was to evaluate whether an increased risk of thyroid cancer exists among women with breast cancer in Taiwan, particularly among those receiving RT. We used data from the National Health Insurance system of Taiwan for the investigation. The breast cancer cohort contained 55,318 women (including 28,187 who received RT and 27,131 who received no RT), each of whom was randomly frequency matched according to age and index year with three women without breast cancer from the general population. Cox's proportion hazards regression analysis was conducted to estimate the effects of breast cancer with or without RT treatment on subsequent thyroid cancer risk. We found that women with breast cancer exhibited a significantly higher risk of subsequent thyroid cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.60-2.44). The two groups (with or without RT) in the breast cancer cohort exhibited significantly increased risks. However, in the breast cancer cohort, the risk of thyroid cancer among women who received RT was not significantly higher than that of women who received no RT (aHR = 1.28, 95% CI = 0.90-1.83). Stratified analysis according to age revealed that only younger women with breast cancer (20-54 y) had a significantly higher risk of developing thyroid cancer. This study determined that Taiwanese women with breast cancer had a higher risk of developing thyroid cancer; however, RT seems to not play a crucial role in this possible relationship. PMID- 26135016 TI - Magnetic resonance imaging of pathogenic protozoan parasite Entamoeba histolytica labeled with superparamagnetic iron oxide nanoparticles. AB - OBJECTIVES: The aim of this study was to establish a noninvasive tracking of the pathogenic parasite Entamoeba histolytica (Eh) after superparamagnetic iron oxide (SPIO) labeling by magnetic resonance imaging (MRI) on a single-cell level in vitro and in vivo in a mouse model for amebic liver abscess (ALA). MATERIALS AND METHODS: Local institutional review committee on animal care approved all animal experiments. Entamoeba histolytica trophozoites were labeled with SPIO nanoparticles (SPIO-Eh). The uptake of SPIO by Eh was optimized using flow cytometry and visualized by bright field, fluorescence, and transmission electron microscopy. The viability of SPIO-Eh was assessed in vitro by determination of growth and ingestion rate of red blood cells. Migration of SPIO-Eh was proven by in vitro MRI in a preclinical 7 T MRI system using continually repeated MRI scans. In vivo distribution of SPIO-Eh within the mouse liver was assessed qualitatively and quantitatively by serial respiration-triggered T2*-weighted MRI, T2-weighted MRI, and R2* MR relaxometry up to 5 days after injection and correlated with immunohistology of the liver sections after removal. RESULTS: Entamoeba histolytica can be efficiently labeled with SPIO without influence on parasite growth rate or phagocytic capacity. In vitro dynamic MRI allowed real time migration monitoring and determination of velocity of single SPIO-Eh. In vivo SPIO-Eh showed signal decrease in T2*-weighted and increase of R2* in ALA formations. Motility of SPIO-Eh was necessary to induce ALA formations. CONCLUSIONS: The present study demonstrates the feasibility of an efficient magnetic labeling and a noninvasive in vitro and in vivo MR tracking of the pathogenic protozoan Eh in a mouse model for ALA, thus representing in future a noninvasive imaging tool to study parasite, as well as on host-specific pathomechanisms. PMID- 26135017 TI - Multiparametric MRI With Dynamic Contrast Enhancement, Diffusion-Weighted Imaging, and 31-Phosphorus Spectroscopy at 7 T for Characterization of Breast Cancer. AB - OBJECTIVES: To describe and to correlate tumor characteristics on multiparametric 7 tesla (T) breast magnetic resonance imaging (MRI) with prognostic characteristics from postoperative histopathology in patients with breast cancer. MATERIALS AND METHODS: Institutional review board approval and written informed consent of 15 women (46-70 years) with 17 malignant lesions were obtained. In this prospective study (March 2013 to March 2014), women were preoperatively scanned using dynamic contrast-enhanced MRI, diffusion-weighted imaging, and 31 phosphorus spectroscopy (13P-MRS). The value of the protocol was assessed to quantify tumor differentiation and proliferation. Dynamic contrast-enhanced MRI was assessed according to the American College of Radiology Breast Imaging Reporting and Data System-MRI lexicon. Apparent diffusion coefficients (ADCs) were calculated from diffusion-weighted imaging. On 13P-MRS, at the location of the tumor, the amount of phosphorus components was obtained in a localized spectrum. In this spectrum, the height of phosphodiester (PDE) and phosphomonoester (PME) peaks was assessed to serve as a measure for metabolic activity, stratifying tumors into a PDE > PME, PDE = PME, or PDE < PME group. Tumor grade and mitotic count from resection specimen were compared with the MRI characteristics using explorative analyses. RESULTS: On dynamic contrast-enhanced MRI, the mean tumor size was 24 mm (range, 6-55 mm). An inverse trend was seen between ADC and tumor grade (P = 0.083), with mean ADC of 867 * 10-6 mm2/s for grade 1 (N = 4), 751 * 10-6 mm2/s for grade 2 (N = 6), and 659 * 10-6 mm2/s for grade 3 (N = 2) tumors. Between P-MR spectra and mitotic count, a relative increase of PME over PDE showed significant association with increasing mitotic counts (P = 0.02); a mean mitotic count of 6 was found in the PDE greater than PME group (N = 7), 8 in the PDE = PME group (N = 1), and 17 in the PDE < PME group (N = 3). CONCLUSIONS: Multiparametric 7 T breast MRI is feasible in clinical setting and shows association between ADC and tumor grade, and between 13P-MRS and mitotic count. PMID- 26135019 TI - Evolution in Computed Tomography: The Battle for Speed and Dose. AB - The advent of computed tomography (CT) has revolutionized radiology. Starting as head-only scanners, modern CT systems are now capable of performing whole-body examinations within a couple of seconds in isotropic resolution. Technical advancements of scanner hardware and image reconstruction techniques are reviewed and discussed in their clinical context. These improvements have led to a steady increase of CT examinations in all age groups for a number of reasons. On the one hand, it is very easy today to obtain whole-body data for oncologic staging and follow-up or for trauma imaging. On the other hand, new examinations such as cardiac imaging, virtual colonoscopy, gout imaging, and whole-organ perfusion imaging have widened the application profile of CT. The increasing awareness of risks associated with radiation exposure triggered the development of a variety of dose reduction techniques. Effective dose values below 1 mSv, less than the annual natural background radiation (3.1 mSv/year on average in the United States), are now routinely possible for a number of dedicated examinations, even for coronary CT angiography. PMID- 26135018 TI - Optical Verification of Microbubble Response to Acoustic Radiation Force in Large Vessels With In Vivo Results. AB - OBJECTIVE: The objective of this study was to optically verify the dynamic behaviors of adherent microbubbles in large blood vessel environments in response to a new ultrasound technique using modulated acoustic radiation force. MATERIALS AND METHODS: Polydimethylsiloxane (PDMS) flow channels coated with streptavidin were used in targeted groups to mimic large blood vessels. The custom-modulated acoustic radiation force beam sequence was programmed on a Verasonics research scanner. In vitro experiments were performed by injecting a biotinylated lipid perfluorobutane microbubble dispersion through flow channels. The dynamic response of adherent microbubbles was detected acoustically and simultaneously visualized using a video camera connected to a microscope. In vivo verification was performed in a large abdominal blood vessel of a murine model for inflammation with injection of biotinylated microbubbles conjugated with P selectin antibody. RESULTS: Aggregates of adherent microbubbles were observed optically under the influence of acoustic radiation force. Large microbubble aggregates were observed solely in control groups without targeted adhesion. Additionally, the dispersion of microbubble aggregates were demonstrated to lead to a transient acoustic signal enhancement in control groups (a new phenomenon we refer to as "control peak"). In agreement with in vitro results, the control peak phenomenon was observed in vivo in a murine model. CONCLUSIONS: This study provides the first optical observation of microbubble-binding dynamics in large blood vessel environments with application of a modulated acoustic radiation force beam sequence. With targeted adhesion, secondary radiation forces were unable to produce large aggregates of adherent microbubbles. Additionally, the new phenomenon called control peak was observed both in vitro and in vivo in a murine model for the first time. The findings in this study provide us with a better understanding of microbubble behaviors in large blood vessel environments with application of acoustic radiation force and could potentially guide future beam sequence designs or signal processing routines for enhanced ultrasound molecular imaging. PMID- 26135020 TI - Donor-anion interactions at the charge localization and charge ordering transitions of (TMTTF)2AsF6 probed by NEXAFS. AB - High-resolution near-edge X-ray absorption fine structure (NEXAFS) measurements at the As M-edge, F K-edge and S L-edge of the Fabre salt (TMTTF)2AsF6 were performed from room temperature (RT) to 90 K, allowing to reach the charge localization regime below Trho ~ 230 K and to cross the charge ordering (CO) transition at TCO ~ 102 K. The F K-edge and S L-edge spectra exhibit several transitions which have been indexed on the basis of first-principles DFT calculations. Upon cooling from RT significant energy shifts up to +0.8 eV and 0.4 eV were observed in transitions exhibited by the F 1s and S 2p spectra respectively, while the As 3p doublet does not show a significant shift. Opposite energy shifts found in the F 1s and S 2p spectra reflect substantial thermal changes in the electronic environment of F atoms of the anion and S atoms of TMTTF. The changes found around the charge localization crossover suggest an increase of the participation of the S d orbitals in the empty states of TMTTF as well as an increase of the strength of donoranion interactions. A new F 1s pre edge signal detected upon entry into the CO phase is a clear fingerprint of the symmetry breaking occurring at TCO. We propose that this new transition is caused by a substantial mixing between the HOMO of the AsF6(-) anion and the unoccupied part of the TMTTF HOMO conduction band. Analysis of the whole spectra also suggests that the loss of the inversion symmetry associated with the CO is due to an anion displacement increasing the strength of SF interactions. Our data show unambiguously that anions are not, as previously assumed, innocent spectators during the electronic modifications experienced by the Fabre salts upon cooling. In particular the interpretation of the spectra pointing out a thermally dependent mixing of anion wave functions with those of the TMTTF chains demonstrates for the first time the importance of anion-donor interactions. PMID- 26135021 TI - Theoretical Study of Light Trapping in Nanostructured Thin Film Solar Cells Using Wavelength-Scale Silver Particles. AB - We propose and theoretically evaluate a plasmonic light trapping solution for thin film photovoltaic devices that comprises a monolayer or a submonolayer of wavelength-scale silver particles. We systematically study the effect of silver particle size using full-wave electromagnetic simulations. We find that light trapping is significantly enhanced when wavelength-scale silver particles rather than the ones with subwavelength dimensions are used. We demonstrate that a densely packed monolayer of spherical 700 nm silver particles enhances integrated optical absorption under standard air mass 1.5 global (AM1.5G) in a 7 MUm-thick N719-sensitized solar cell by 40% whereas enhancement is smaller than 2% when 100 nm ones are used. Superior performance of wavelength-scale silver particles is attributed to high-order whispering gallery modes that they support. These modes scatter the light over a wider angular range, hence increasing the density of both waveguide and resonance modes within the dye-sensitized layer. PMID- 26135022 TI - ADHD stigma among college students. AB - The current study examined ADHD stigma within a college-enrolled young adult population, including the debate regarding the cause of stigma: label or behavior. In Phase 1, 135 college students rated stigma toward one of the four fictitious partners described as having either: the label of ADHD alone, the behaviors associated with ADHD alone, the label of ADHD and a set of behaviors associated with ADHD, or neither the label nor behaviors. In Phase 2, 48 college students rated stigma toward one of the two assigned fictitious partners described as having either: the label of ADHD and a set of behaviors associated with ADHD, or the label of Depression and a set of behaviors associated with Depression. It was hypothesized that the interaction between the label and the behaviors would cause the highest levels of ADHD stigma and that ADHD would elicit more stigma than Depression. In Phase 1, stigma was associated with the behaviors of ADHD, but not the label. In Phase 2, ADHD and Depression were found to be equally stigmatized. Implications, limitations, and future directions are discussed. PMID- 26135023 TI - Impact of untreated dental caries and its clinical consequences on the oral health-related quality of life of schoolchildren aged 8-10 years. AB - OBJECTIVE: This study aims to evaluate the impact of untreated dental caries and its clinical consequences on the quality of life of Brazilian schoolchildren aged 8-10 years. METHODS: A randomly selected sample of 587 children underwent a clinical oral examination for the assessment of untreated dental caries and clinical consequences. The WHO criteria (decayed component of the decayed, missing, and filled teeth--D-DMFT in permanent teeth or d-dfmt in primary teeth) and the PUFA index, which records the presence of severely decayed permanent (upper case) and primary (lower case) teeth with visible pulpal involvement (P/p), as well as ulceration caused by dislocated tooth fragments (U/u), fistula (F/f), and abscesses (A/a), were used for the oral examination. Oral health related quality of life (OHRQoL) was evaluated using the Child's Perception Questionnaire (CPQ8-10). Poisson regression was employed to test unadjusted and adjusted associations between untreated dental caries/clinical consequences and OHRQoL. RESULTS: The prevalence of untreated dental caries was 64.6% (D/d component of DMFT/dmft > 0) and 17.9% of children exhibited clinical consequences of caries (PUFA/pufa index >0). In the adjusted models, untreated caries was significantly associated with the total CPQ8-10 score and all subscale scores. The clinical consequences of dental caries (PUFA/pufa index >0) were significantly associated with the total CPQ8-10 as well as the oral symptoms and functional limitations' subscales. CONCLUSION: Untreated dental caries and its clinical consequences exerted a negative impact on the OHRQoL of the schoolchildren analyzed. PMID- 26135024 TI - Inflammatory Diseases of the Lung Induced by Conventional Cigarette Smoke: A Review. AB - Smoking-induced lung diseases were extremely rare prior to the 20th century. With commercialization and introduction of machine-made cigarettes, worldwide use skyrocketed and several new pulmonary diseases have been recognized. The majority of pulmonary diseases caused by cigarette smoke (CS) are inflammatory in origin. Airway epithelial cells and alveolar macrophages have altered inflammatory signaling in response to CS, which leads to recruitment of lymphocytes, eosinophils, neutrophils, and mast cells to the lungs-depending on the signaling pathway (nuclear factor-kappaB, adenosine monophosphate-activated protein kinase, c-Jun N-terminal kinase, p38, and signal transducer and activator of transcription 3) activated. Multiple proteins are upregulated and secreted in response to CS exposure, and many of these have immunomodulatory activities that contribute to disease pathogenesis. In particular, metalloproteases 9 and 12, surfactant protein D, antimicrobial peptides (LL-37 and human beta defensin 2), and IL-1, IL-6, IL-8, and IL-17 have been found in higher quantities in the lungs of smokers with ongoing inflammation. However, many underlying mechanisms of smoking-induced inflammatory diseases are not yet known. We review here the known cellular and molecular mechanisms of CS-induced diseases, including COPD, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia, acute eosinophilic pneumonia, chronic rhinosinusitis, pulmonary Langerhans cell histiocytosis, and chronic bacterial infections. We also discuss inflammation induced by secondhand and thirdhand smoke exposure and the pulmonary diseases that result. New targeted antiinflammatory therapeutic options are currently under investigation and hopefully will yield promising results for the treatment of these highly prevalent smoking-induced diseases. PMID- 26135025 TI - HCV: the best cure possible or the best possible cure? AB - Progress in medicine goes along with an exponential growth of the cost of drugs and devices. While any person has the right to obtain the best possible benefit from medical care, a state needs to strike a balance between granting the optimal personal benefit to each individual and the needs of the society as a whole. Health systems in all countries therefore are facing a huge problem of distributive justice, as while they should guarantee individual rights, among which the right to health in its broader sense, including physical, psychological and social well-being (therefore not limited to healing, but extending to compliance and quality of life), they must also grant equal access to the healthcare resources and keep the distribution system sustainable. PMID- 26135026 TI - Clinical impact of treatment timing for chronic hepatitis C infection: a decision model. AB - Recent advances in the treatment of hepatitis C virus (HCV) infection have led to the availability of both highly efficacious interferon-containing and interferon sparing regimens. However, the use of such therapies faces restrictions due to high costs. For patients who are medically eligible to receive interferon, the choice between the two will likely be impacted by preferences surrounding interferon, severity of disease, coverage policies and out-of-pocket costs. We developed a decision model to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 HCV infection. We projected the quality-adjusted life expectancy stratified by the presence or absence of cirrhosis for four strategies: (i) no treatment; (ii) immediate, one-time treatment with an interferon-containing regimen; (iii) immediate treatment as above with the opportunity for retreatment in patients who fail to achieve sustained virologic response with interferon-free therapy in 1 year; and (iv) delayed therapy with interferon-free therapy in 1 year. When compared to one-time immediate treatment with the interferon-containing regimen, delayed treatment with the interferon free regimen in 1 year resulted in longer life expectancy, with a 0.2 quality adjusted life year (QALY) increase in noncirrhotic patients, and a 1.1 QALY increase in patients with cirrhosis. This superiority in health benefits was lost when wait time for interferon-free therapy was greater than 3-3.2 years. In this modelling analysis, interferon-free therapy resulted in superior health benefits compared to immediate therapy with interferon until wait time exceeded 3-3.2 years. Such data can inform decision-making regarding treatment initiation for HCV as healthcare financing evolves. PMID- 26135027 TI - Using proteomics to probe neurons. AB - Advances in mass spectrometry-based proteomics have allowed researchers to quantify the abundances of the different forms of three closely related proteins in the neurons of mice. PMID- 26135028 TI - Optical and electron paramagnetic resonance studies of the excited triplet states of UV-B absorbers: 2-ethylhexyl salicylate and homomenthyl salicylate. AB - The energy levels and lifetimes of the lowest excited triplet (T1) states of UV-B absorbers, 2-ethylhexyl salicylate (EHS) and homomenthyl salicylate (HMS), and their deprotonated anions (EHS(-) and HMS(-)) were determined through measurements of phosphorescence and electron paramagnetic resonance (EPR) spectra in rigid solutions at 77 K. The observed T1 energies of EHS and HMS are higher than those of butylmethoxydibenzoylmethane, the most widely used UV-A absorber, and octyl methoxycinnamate, the most widely used UV-B absorber. The T1 states of EHS, HMS, EHS(-) and HMS(-) were assigned to almost pure (3)pipi* state from the observed T1 lifetimes and zero-field splitting parameters. EHS and HMS with an intramolecular hydrogen bond show a photoinduced phosphorescence enhancement in ethanol at 77 K. The EPR signals of the T1 states of EHS and HMS also increase in intensity with UV-irradiation time (photoinduced EPR enhancement). The T1 lifetimes of EHS and HMS at room temperature were determined through triplet triplet absorption measurements in ethanol. The quantum yields of singlet oxygen production by EHS and HMS were determined by using time-resolved near-IR phosphorescence. PMID- 26135029 TI - Rhenium Complex with Noninnocent Dioxolene Ligand: Combined Experimental and ab Initio Study of [(3,5-di-tert-Bu2C6H2O2)ReCl3(OPPh3)]. AB - Reaction of [ReOCl3(PPh3)2] with 3,5-di-tert-butyl-1,2-benzoquinone (3,5-DTBQ) in hot toluene produces a new complex [(3,5-di-tert-Bu2C6H2O2)Re(OPPh3)Cl3] (1), which was isolated and characterized by elemental analysis, IR, UV-vis spectroscopy, and cyclic voltammetry. In order to clarify the charge state of rhenium and the coordinated dioxolene ligand, X-ray experiments at 150 and 290 K were carried out. The C-O, C-C, and Re-O bond distances at both 150 and 290 K fall between those for semiquinolate (3,5-DTBSQ) and catecholate (3,5-DTBCat) forms; an empirical "metrical oxidation state" of the dioxolene ligand was estimated to be -1.5. High-level ab initio calculations (SOC-CASSCF/NEVPT2) revealed a mixed valence nature of the triplet ground state of complex 1 corresponding to a superposition of the Re(IV)-SQ and Re(V)-cat forms. In agreement with the high-level ab initio and DFT calculations, the temperature dependence of the magnetic susceptibility (5-300 K) is well described in the assumption of the triplet ground state, with the anomalously large zero-field splitting (ZFS) arising from the spin-orbit coupling. According to the ab initio calculations, all absorption bands in the visible region of the electronic absorptions spectrum are assigned to the LMCT bands, with significant contribution of the intraligand transition in the most intense band at 555 nm. PMID- 26135030 TI - Modeling of hematologic malignancies by iPS technology. AB - Induced pluripotent stem cells (iPSCs) can be generated from various types of cells with transduction of defined transcription factors. Patient-derived iPSCs are becoming commonly utilized for understanding the molecular pathways involved in disease and for the development of novel targeted therapies. With the use of patient-derived iPSCs differentiated to specific-lineage cells, the potency and toxicity of drug candidates can be evaluated. In the past, patient-derived iPSCs were mainly established from patients of inherited hematologic diseases, followed by the expansion of target to acquired diseases like myeloproliferative neoplasms. Thanks to the rapid development of novel genome editing technologies, we can now utilize genetically modified and unprocessed iPSCs more readily than before. These technologies, which enable us to modulate genetic status or even chromosome structure at the right time, could help the elucidation of pathogenesis of hematologic diseases. If iPSC-derived hematopoietic cells are to be robustly reconstituted in vivo as a consequence of the development of reprogramming and conversion technology, research on leukemic stem cells must be widely promoted. Therefore, iPSC technology has great potential on oncology research using patient samples. PMID- 26135031 TI - MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine. AB - Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2-6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann-grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration. PMID- 26135032 TI - Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice. AB - Matrine, an active constituent of the Chinese herb, Sophora flavescens Ait., and it is known for its antioxidant, anti-inflammatory and antitumor activities. It has been demonstrated that matrine exerts protective effects against heart failure by decreasing the expression of caspase-3 and Bax, and increasing Bcl-2 levels. In this study, we aimed to determine whether these protective effects of matrine can be applied to cerebral ischemia. Following 7 successive days of treatment with matrine (7.5, 15 and 30 mg/kg) and nimodipine (1 mg/kg) by intraperitoneal injection, male Institute of Cancer Research (ICR) mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, the neurobehavioral score and brain infarct volume were estimated, and morphological changes were analyzed by hematoxylin and eosin (H&E) staining and electron microscopy. The percentage of apoptotic neurons was determined by flow cytometry. The levels of oxidative stress were assessed by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH Px) and catalase (CAT), and the total antioxidant capacity (T-AOC). Western blot analysis and immunofluorescence staining were used to examine the expression of the apoptosis-related proteins, caspase-3, Bax and Bcl-2. Our results revealed that pre-treatment with matrine significantly decreased the infarct volume and improved the neurological scores. Matrine also reduced the percentage of apoptotic neurons and relieved neuronal morphological damage. Furthermore, matrine markedly decreased the MDA levels, and increased SOD, GSH-Px and CAT activity, and T-AOC. Western blot analysis and immunofluorescence staining revealed a marked decrease in caspase-3 expression and an increase in the Bcl 2/Bax ratio in the group pre-treated with matrine (30 mg/kg) as compared with the vehicle-treated group. The findings of the present study demonstrate that matrine exerts neuroprotective effects against cerebral ischemic injury and that these effects are associated with its antioxidant and anti-apoptotic properties. PMID- 26135033 TI - Controlled release of anti-diabetic drug Gliclazide from poly(caprolactone)/poly(acrylic acid) hydrogels. AB - Drug Gliclazide (Glz) has limited solubility and low bioavailability. In order to obtain a controlled release of this drug and to improve its bioavailability, the drug has been loaded into poly(caprolactone) (PCL)/poly(acrylic acid) (PAAc) hydrogels, prepared by free radical polymerization of acrylic acid in the presence of poly(caprolactone) in acetone medium using azo-isobutyronitrile as initiator and N,N' methylene bisacrylamide as cross-linking agent. The swelling behaviour of these hydrogels has been investigated in the physiological gastric and intestinal fluids to obtain an optimum composition suitable for delivery of a biologically active compound. The gels were loaded with anti-diabetic drug Glz and a detailed investigation of release of drug has been carried out. Various kinetic models have been applied on the release data. Finally, the Albino wistar rats were treated for Streptozotocin plus nicotinamide - induced diabetes using a Glz-loaded PCL/PAAc hydrogel. The results indicated a fair reduction in the glucose level of rats. PMID- 26135034 TI - Mycolic acids: deciphering and targeting the Achilles' heel of the tubercle bacillus. AB - Mycolic acids are unique long chain fatty acids found in the lipid-rich cell walls of mycobacteria including the tubercle bacillus Mycobacterium tuberculosis. Essential for viability and virulence, enzymes involved in the biosynthesis of mycolic acids represent novel targets for drug development. This is particularly relevant to the impact on global health given the rise of multidrug resistant and extensively drug resistant strains of M. tuberculosis. In this review, we discuss recent advances in our understanding of how mycolic acid are synthesised, especially the potential role of specialised fatty acid synthase complexes. Also, we examine the role of a recently reported mycolic acid transporter MmpL3 with reference to several reports of the targeting of this transporter by diverse compounds with anti-M. tuberculosis activity. Additionally, we consider recent findings that place mycolic acid biosynthesis in the context of the cell biology of the bacterium, viz its localisation and co-ordination with the bacterial cytoskeleton, and its role beyond maintaining cell envelope integrity. PMID- 26135035 TI - Long follow-up time and different sensitivities of cancer types may have obscured the effect of 25-hydroxyvitamin D on cancer incidence and mortality rates. PMID- 26135036 TI - Reply to WB Grant. PMID- 26135038 TI - Facile Gold-Catalyzed Heterocyclization of Terminal Alkynes and Cyanamides Leading to Substituted 2-Amino-1,3-Oxazoles. AB - Facile gold-catalyzed heterocyclization based upon intermolecular trapping of the generated alpha-oxo gold carbenes with various cyanamides R(2)R(3)NCN (R(2)/R(3) = Alk/Alk, -(CH2)2O(CH2)2-, Ar/Ar, Ar/H) has been developed. In most cases, 2 amino-1,3-oxazoles functionalized at the nitrogen atom as well as at the fifth position of the heterocyclic ring (12 examples) were isolated in good to moderate yields. PMID- 26135039 TI - Determination of the Reaction Coordinate for a Key Conformational Fluctuation in Human Carbonic Anhydrase II. AB - During the reversible hydration of carbon dioxide into bicarbonate by the enzyme human carbonic anhydrase II, the rate-determining step of proton transfer across the active site has been suggested to involve side chain rotation of the residue His-64 shuttling an excess proton in and out of the active site. In the present article, we have determined the reaction coordinate for this catalytically important conformational transition starting from a set of 32 order parameters (or candidate collective variables). Following the original work by Peters and Trout (J. Chem. Phys. 2006, 125, 054108), unbiased dynamical transition paths connecting the two major side chain conformations are harvested using an aimless shooting algorithm, and the reaction coordinate is determined using the method of forward-trajectory likelihood maximization. Several different models are tested involving a single order parameter or linear combinations of several of them chosen from the preselected set. An optimum reaction coordinate, identified using a Bayesian information criterion, is found to be a linear combination of 4 order parameters. This reaction coordinate is subsequently utilized to explore the associated free energy profile and diffusive barrier crossing dynamics. To the best of our knowledge, previous instances of this calculation include only alanine dipeptide and photoactive yellow protein (125 residues) in explicit water solvent. The present work is the first report of a quantitative determination of the reaction coordinate for conformational transition in a protein having as many as 259 residues in the presence of explicit water and sampled near the free energy barrier for about 1 MUs. PMID- 26135040 TI - Occurrence of adverse events among patients with inflammatory bowel disease in the HealthCore Integrated Research Database. AB - OBJECTIVES: Inflammatory bowel disease (IBD) is a chronic condition commonly requiring lifelong care. Both IBD and IBD-related treatments can cause significant morbidity, and it is often difficult to differentiate their relative etiologic contribution to adverse events (AEs). The objectives of this study were to assess the rates of select AEs among patients with IBD as a function of disease severity and of the use of anti-tumor necrosis factor alpha (anti TNFalpha) medications. METHODS: We conducted a retrospective cohort study of IBD patients in the HealthCore Integrated Research Database (HIRD(TM)) between January 2004 and January 2011 to determine rates of AEs in patients with mild and moderate to severe IBD. Key study endpoints were select prespecified malignant neoplasms, infections, and other AEs of interest. RESULTS: A total of 33,386 IBD patients (52.7% ulcerative colitis; 47.3% Crohn's disease) met the inclusion criteria, and 60% had been followed for >=1 year. Patients with moderate to severe IBD had increased rates of infections, lymphatic and digestive tract cancers, gastrointestinal (GI) perforations, and myocardial infarctions versus patients with mild IBD. Patients with IBD who used anti-TNFalpha therapies during the study had increased incidence of many types of infections, certain GI cancers (including rectal and anal cancer), intestinal perforations, and kidney stones compared with patients who had never used anti-TNFalpha therapies. CONCLUSIONS: Results from this large US cohort provide descriptive information on AE rates in a population of IBD patients undergoing routine care, estimating background incidence rates of AEs that are not readily available in the published literature. Our study findings may be limited owing to a lack of generalizability and potential for misclassification due to reliance on medical diagnosis and treatment and procedure codes to identify disease, comorbidities, and treatments. Further research and validation of our findings in other populations and databases are needed. PMID- 26135041 TI - Rate and Equilibrium Constants for an Enzyme Conformational Change during Catalysis by Orotidine 5'-Monophosphate Decarboxylase. AB - The caged complex between orotidine 5'-monophosphate decarboxylase (ScOMPDC) and 5-fluoroorotidine 5'-monophosphate (FOMP) undergoes decarboxylation ~300 times faster than the caged complex between ScOMPDC and the physiological substrate, orotidine 5'-monophosphate (OMP). Consequently, the enzyme conformational changes required to lock FOMP at a protein cage and release product 5-fluorouridine 5' monophosphate (FUMP) are kinetically significant steps. The caged form of ScOMPDC is stabilized by interactions between the side chains from Gln215, Tyr217, and Arg235 and the substrate phosphodianion. The control of these interactions over the barrier to the binding of FOMP and the release of FUMP was probed by determining the effect of all combinations of single, double, and triple Q215A, Y217F, and R235A mutations on kcat/Km and kcat for turnover of FOMP by wild-type ScOMPDC; its values are limited by the rates of substrate binding and product release, respectively. The Q215A and Y217F mutations each result in an increase in kcat and a decrease in kcat/Km, due to a weakening of the protein phosphodianion interactions that favor fast product release and slow substrate binding. The Q215A/R235A mutation causes a large decrease in the kinetic parameters for ScOMPDC-catalyzed decarboxylation of OMP, which are limited by the rate of the decarboxylation step, but much smaller decreases in the kinetic parameters for ScOMPDC-catalyzed decarboxylation of FOMP, which are limited by the rate of enzyme conformational changes. By contrast, the Y217A mutation results in large decreases in kcat/Km for ScOMPDC-catalyzed decarboxylation of both OMP and FOMP, because of the comparable effects of this mutation on rate determining decarboxylation of enzyme-bound OMP and on the rate-determining enzyme conformational change for decarboxylation of FOMP. We propose that kcat = 8.2 s(-1) for decarboxylation of FOMP by the Y217A mutant is equal to the rate constant for cage formation from the complex between FOMP and the open enzyme, that the tyrosyl phenol group stabilizes the closed form of ScOMPDC by hydrogen bonding to the substrate phosphodianion, and that the phenyl group of Y217 and F217 facilitates formation of the transition state for the rate-limiting conformational change. An analysis of kinetic data for mutant enzyme-catalyzed decarboxylation of OMP and FOMP provides estimates for the rate and equilibrium constants for the conformational change that traps FOMP at the enzyme active site. PMID- 26135042 TI - A nonlinear contextually aware prompting system (N-CAPS) to assist workers with intellectual and developmental disabilities to perform factory assembly tasks: system overview and pilot testing. AB - PURPOSE: This paper presents a new cognitive assistive technology, nonlinear contextually aware prompting system (N-CAPS) that uses advanced sensing and artificial intelligence to monitor and provide assistance to workers with cognitive disabilities during a factory assembly task. METHODS: The N-CAPS system was designed through the application of various computer vision and artificial intelligence algorithms that allows the system to track a user during a specific assembly task, and then provide verbal and visual prompts to the worker as needed. A pilot study was completed with the N-CAPS solution in order to investigate whether it was an appropriate intervention. Four participants completed the required assembly task five different times, using the N-CAPS system. RESULTS: The participants completed all of the trials that they attempted with 85.7% of the steps completed without assistance from the job coach. Of the 85.7% of steps completed independently, 32.5% of these were completed in response to prompts given by N-CAPS. Overall system accuracy was 83.3%, the overall sensitivity was 86.2% and the overall specificity was 82.4%. CONCLUSIONS: The results from the study were positive in that they showed that this type of technology does have merit with this population. Implications for Rehabilitation It provides a concise summary of the importance of work in the lives of people with intellectual disabilities and how technology can support this life goal. It describes the first artificially intelligent system designed to support workers with intellectually disabilities. It provides evidence that individuals with intellectual disabilities can perform a work task in response to technology. PMID- 26135043 TI - Patents for Toll-like receptor ligands as radiation countermeasures for acute radiation syndrome. AB - Acute radiation exposure induces apoptosis of tissues in the hematopoietic, digestive, cutaneous, cardiovascular and nervous systems; extensive apoptosis of these tissues ultimately leads to acute radiation syndrome. A novel strategy for developing radiation countermeasures has been to imitate the genetic mechanisms acquired by radiation-resistant tumors. Two mechanisms that underlie this ability of tumor cells are the p53 and NF-kappaB pathways. The loss of p53 function results in the inactivation of pro-apoptotic control mechanisms, while constitutive activation of NF-kappaB results in the up-regulation of anti apoptotic genes. Various Toll-like receptor ligands are capable of up regulating the NF-kappaB pathway, which increases radio-resistance and reduces radiation induced apoptosis in various tissues. Several Toll-like receptor ligands have been patented and are currently under development as radiation countermeasures for acute radiation syndrome. Ongoing studies suggest that a few of these attractive agents are progressing well along the US FDA approval pathway to become radiation countermeasures. PMID- 26135046 TI - Templateless Synthesis of Polyacrylamide-Based Nanogels via RAFT Dispersion Polymerization. PMID- 26135049 TI - One-Pot Synthesis of Copper Sulfide Nanowires/Reduced Graphene Oxide Nanocomposites with Excellent Lithium-Storage Properties as Anode Materials for Lithium-Ion Batteries. AB - Copper sulfide nanowires/reduced graphene oxide (CuSNWs/rGO) nanocompsites are successfully synthesized via a facile one-pot and template-free solution method in a dimethyl sulfoxide (DMSO)-ethyl glycol (EG) mixed solvent. It is noteworthy that the precursor plays a crucial role in the formation of the nanocomposites structure. SEM, TEM, XRD, IR and Raman spectroscopy are used to investigate the morphological and structural evolution of CuSNWs/rGO nanocomposites. The as fabricated CuSNWs/rGO nanocompsites show remarkably improved Li-storage performance, excellent cycling stability as well as high-rate capability compared with pristine CuS nanowires. It obtains a reversible capacity of 620 mAh g(-1) at 0.5C (1C = 560 mA g(-1)) after 100 cycles and 320 mAh g(-1) at a high current rate of 4C even after 430 cycles. The excellent lithium storage performance is ascribed to the synergistic effect between CuS nanowires and rGO nanosheets. The as-formed CuSNWs/rGO nanocomposites can effectively accommodate large volume changes, supply a 2D conducting network and trap the polysulfides generated during the conversion reaction of CuS. PMID- 26135050 TI - Nanopaper as an Optical Sensing Platform. AB - Bacterial cellulose nanopaper (BC) is a multifunctional material known for numerous desirable properties: sustainability, biocompatibility, biodegradability, optical transparency, thermal properties, flexibility, high mechanical strength, hydrophilicity, high porosity, broad chemical-modification capabilities and high surface area. Herein, we report various nanopaper-based optical sensing platforms and describe how they can be tuned, using nanomaterials, to exhibit plasmonic or photoluminescent properties that can be exploited for sensing applications. We also describe several nanopaper configurations, including cuvettes, plates and spots that we printed or punched on BC. The platforms include a colorimetric-based sensor based on nanopaper containing embedded silver and gold nanoparticles; a photoluminescent-based sensor, comprising CdSe@ZnS quantum dots conjugated to nanopaper; and a potential up-conversion sensing platform constructed from nanopaper functionalized with NaYF4:Yb(3+)@Er(3+)&SiO2 nanoparticles. We have explored modulation of the plasmonic or photoluminescent properties of these platforms using various model biologically relevant analytes. Moreover, we prove that BC is and advantageous preconcentration platform that facilitates the analysis of small volumes of optically active materials (~4 MUL). We are confident that these platforms will pave the way to optical (bio)sensors or theranostic devices that are simple, transparent, flexible, disposable, lightweight, miniaturized and perhaps wearable. PMID- 26135051 TI - Inhibitory effect of TGF-beta peptide antagonist on the fibrotic phenotype of human hypertrophic scar fibroblasts. AB - CONTEXT: TGF-beta plays a central role in hypertrophic scar (HS) formation and development. OBJECTIVE: This study investigated the role of a TGF-beta antagonist peptide in inhibiting fibrotic behavior of human HS-derived fibroblasts (HSFs). MATERIALS AND METHODS: HSFs were seeded at a density of 3.1 * 10(4)/cm(2) and were subjected to treatment of peptide antagonist (30 MUM) or TGF-beta receptor inhibitor LY2109761 (10 MUM) or without treatment followed by the analyses of quantitative PCR, Elisa, in vitro wounding and fibroblast-populated collagen lattice (FPCL) assays. RESULTS: qPCR and Elisa analyses showed that the peptide could, respectively, reduce the gene (at 48 h) and protein (at 72 h) expression levels of collagen I (86 +/- 4.8%; 56.6 +/- 7.3%), collagen III (73 +/- 10.7%; 43.7 +/- 7.2%), fibronectin (90 +/- 8.9%; 21.1 +/- 2.8%), and TGF-beta1 (85 +/- 9.3%; 25.0 +/- 9.4%) as opposed to the non-treated group (p < 0.05), as the LY2109761 group similarly did. Cell proliferation was also significantly inhibited at day 5 (CCK-8 assay) by both peptide and LY2109761 treatments compared with the non-treated group (p < 0.05). The peptide also significantly inhibited cell migration as opposed to blank control at 24 h (43 +/- 6.7% versus 60 +/- 2.1%, p < 0.05) and at 48 h (63.9 +/- 3.1% versus 95 +/- 4.1%, p < 0.05). Similar to LY2109761, the peptide antagonist significantly reduced HS FPCL contraction compared with the non-treated group with significant differences in surface area at 48 h (0.71 +/- 0.06 cm(2) versus 0.51 +/- 0.06 cm(2), p < 0.05) and at 72 h (0.65 +/- 0.02 cm(2) versus 0.42 +/- 0.01 cm(2), p < 0.05). CONCLUSION: The TGF-beta antagonist peptide may serve as an important drug for HS prevention and reduction given the obvious benefits of good biosafety, low cost, and easy manufacture and delivery. PMID- 26135052 TI - In Memoriam - Lester A. Mitscher (1931-2015). PMID- 26135053 TI - One-shot access to alpha,beta-difunctionalized azepenes and dehydropiperidines by reductive cross-coupling of alpha-selenonyl-beta-selenyl enamides with organic bromides. AB - The synthesis of alpha- and alpha,beta-functionalized azepenes and dehydropiperidines from readily prepared alpha-selenonyl eneformamides or enecarbamates has been achieved through Fe-catalyzed alpha-substitutive deselenonation, beta-regioselective lithiation/trapping, and Co-catalyzed reductive cross-coupling protocols. PMID- 26135054 TI - Eco-friendly approach towards green synthesis of zinc oxide nanocrystals and its potential applications. AB - In the present study, we investigated a novel green route for synthesis of zinc oxide (ZnO) nanocrystals using Prunus * yedoensis Matsumura leaf extract as a reducing agent without using any surfactant or external energy. Standard characterization studies were carried out to confirm the obtained product using UV-Vis spectra, SEM-EDS, FTIR, TEM, and XRD. In addition, the synthesized ZnO nanocrystals were coated onto fabric and leather samples to study their bacteriostatic effect against odor-causing bacteria Brevibacterium linens and Staphylococcus epidermidis. Zinc oxide nanocrystal-coated fabric and leather showed good activity against both bacteria. PMID- 26135055 TI - Risk factors for in-hospital mortality among a cohort of children with Clostridium difficile infection. AB - OBJECTIVE: The incidence of Clostridium difficile infection (CDI) has increased and has been associated with poor outcomes among hospitalized children, including increased risk of death. The purpose of this study was to identify risk factors for all-cause in-hospital mortality among children with CDI. METHODS: A multicenter cohort of children with CDI, aged 1-18 years, was established among children hospitalized at 41 freestanding children's hospitals between January 1, 2006 and August 31, 2011. Children with CDI were identified using a validated case-finding tool (ICD-9-CM code for CDI plus C. difficile test charge). Only the first CDI-related hospitalization during the study period was used. Risk factors for all-cause in-hospital mortality within 30 days of C. difficile test were evaluated using a multivariable logistic regression model. RESULTS: We identified 7,318 children with CDI during the study period. The median age of this cohort was 6 years [interquartile range (IQR): 2-13]; the mortality rate was 1.5% (n=109); and the median number of days between C. difficile testing and death was 12 (IQR, 7-20). Independent risk factors for death included older age [adjusted odds ratio (OR, 95% confidence interval), 2.29 (1.40-3.77)], underlying malignancy [3.57 (2.36-5.40)], cardiovascular disease [2.06 (1.28-3.30)], hematologic/immunologic condition [1.89 (1.05-3.39)], gastric acid suppression [2.70 (1.43-5.08)], and presence of >1 severity of illness marker [3.88 (2.44 6.19)]. CONCLUSION: Patients with select chronic conditions and more severe disease are at increased risk of death. Identifying risk factors for in-hospital mortality can help detect subpopulations of children that may benefit from targeted CDI prevention and treatment strategies. PMID- 26135056 TI - Erratum to: Molecular and cellular mechanisms that initiate pain and itch. PMID- 26135057 TI - Conjugation-Induced Rigidity in Twisting Molecules: Filling the Gap Between Aggregation-Caused Quenching and Aggregation-Induced Emission. AB - Conjugation-induced rigidity in twisting molecules provides a new facile but effective avenue toward solution and solid dual-state efficient luminogens. While conjugation rigidifies the molecular conformations in solution, the twisting structure prevents or alleviates detrimental close molecular packing in the solid states, thus synergistically yielding high efficiencies in both solution and solid states. PMID- 26135058 TI - Two new isoflavone 7-O-alpha-4"-anhydro-4",5"-didehydroglucuronides from Streptomyces sp. LZ35DeltagdmAI. AB - Two isoflavone 7-O-alpha-4"-anhydro-4",5"-didehydroglucuronides, namely daidzein 7-O-alpha-4"-anhydro-4",5"-didehydroglucuronide (1) and genistein 7-O-alpha-4" anhydro-4",5"-didehydroglucuronide (2), were isolated and identified from the mutant strain of Streptomyces sp. LZ35DeltagdmAI. Their structures were elucidated by the analysis of their high resolution mass spectrometry (HR-MS) and 1D, 2D Nuclear magnetic Resonance (NMR) spectroscopic data. They are new natural products and maybe the transformed products of the soybean meal by Streptomyces sp. LZ35DeltagdmAI. PMID- 26135059 TI - Is Perceptual Priming Affected by Culture? A Study With German Middle-Class and Cameroonian Nso Farmer Children. AB - The authors explored priming in children from different cultural environments with the aim to provide further evidence for the robustness of the priming effect. Perceptual priming was assessed by a picture fragment completion task in 3-year-old German middle-class and Cameroonian Nso farmer children. As expected, 3-year-olds from both highly diverging cultural contexts under study showed a priming effect, and, moreover, the effect was of comparable size in both cultural contexts. Hence, the children profited similarly from priming, which was supported by the nonsignificant interaction between cultural background and identification performance as well as the analysis of absolute difference scores. However, a culture-specific difference regarding the level of picture identification was found in that German middle-class children identified target as well as control pictures with less perceptual information than children in the Nso sample. Explanations for the cross-cultural demonstration of the priming effect as well as for the culturally diverging levels on which priming occurs are discussed. PMID- 26135060 TI - [Report from the managing board]. PMID- 26135061 TI - [President's report]. PMID- 26135062 TI - Practice Patterns in Pediatric Critical Care Medicine: Results of a Workforce Survey. AB - OBJECTIVE: To obtain current data on practice patterns of the U.S. pediatric critical care medicine workforce. DATA SOURCES: Membership of the American Academy of Pediatrics Section on Critical Care and individuals certified by the American Board of Pediatrics in pediatric critical care medicine. STUDY SELECTION: All active members of the American Academy of Pediatrics Section on Critical Care, and nonduplicative individuals certified by the American Board of Pediatrics in pediatric critical care medicine, were classified as eligible to participate in this electronically administered workforce survey. DATA EXTRACTION: Data were extracted by a doctorate-level research professional. Extracted data included demographic information, work environment, number of hours worked, training, clinical responsibilities, work satisfaction and burnout, and plans to leave the practice of pediatric critical care medicine. DATA SYNTHESIS: Of 1,857 individuals contacted, 923 completed the survey (49.7%). The majority of respondents were white, male, non-Hispanic, university-employed, and taught residents. Respondents who worked full time were on clinical intensive care service for a median of 15 wk/yr and responsible for a median of 13 ICU beds, working a median of 60 hr/wk. Total night call responsibility was a median of 60 nights/yr; about half of respondents indicated night call was in-hospital. Fewer than half were engaged in basic science or clinical research. Compared with earlier data, there was minimal change in work hours and proportion of time devoted to research, but there was an increase in the proportion of female pediatric critical care medicine physicians. CONCLUSIONS: These data provide a description of the typical intensivist and a snapshot of the current pediatric critical care medicine workforce, which may be experiencing a mild-to-moderate undersupply. The results are useful for assessing the current workforce and valuable for future planning. PMID- 26135063 TI - Ultrasound Imaging Reduces Failure Rates of Percutaneous Central Venous Catheterization in Children. AB - OBJECTIVE: Ultrasound imaging has been shown to be beneficial for percutaneous central venous cannulation in systematic reviews of randomized controlled trials in adult patients, but not in pediatrics. The aim of this updated review was to determine whether percutaneous central venous catheterization with the aid of ultrasound reduces cannulation failure in children. DATA SOURCES: PubMed was searched using the terms: ultrasound, catheterization, central vein (including internal jugular and femoral veins), and pediatrics. STUDY SELECTION: Both nonrandomized comparative studies and randomized controlled trials were eligible for inclusion if they assessed the rate of cannulation failure using real-time, dynamic ultrasound guidance, ultrasound-assisted vein prelocation, and/or anatomic landmark technique. DATA EXTRACTION: Five nonrandomized studies and nine randomized controlled trials were included. The rates of cannulation failure and arterial puncture were retrieved. DATA SYNTHESIS: Random-effects meta-analysis was applied. CONCLUSIONS: The meta-analysis of five nonrandomized studies showed that the rate of cannulation failure was significantly lower with real-time ultrasound guidance than anatomic landmark technique (odds ratio, 0.44 [95% CI, 0.27-0.72]; p = 0.001). The combination of nine randomized controlled trials also showed lower failure rates with either the real-time ultrasound guidance or the prelocation technique over the landmark technique (odds ratio, 0.22 [95% CI, 0.07 0.69]; p = 0.0003) and fewer arterial punctures in the ultrasound group (odds ratio, 0.31 [95% CI, 0.09-1.08]; p = 0.07). However, seven out of nine studies were assessed as having high risk of bias. Since the lower cannulation failure and less frequent chance of arterial puncture with ultrasound were predominantly shown in studies at high risk of bias, further definitive and adequately powered studies with clear outcomes are needed. PMID- 26135064 TI - Developing a Family-Centered Care Model for Critical Care After Pediatric Traumatic Brain Injury. AB - OBJECTIVES: This study examined the family experience of critical care after pediatric traumatic brain injury in order to develop a model of specific factors associated with family-centered care. DESIGN: Qualitative methods with semi structured interviews were used. SETTING: Two level 1 trauma centers. PARTICIPANTS: Fifteen mothers of children who had an acute hospital stay after traumatic brain injury within the last 5 years were interviewed about their experience of critical care and discharge planning. Participants who were primarily English, Spanish, or Cantonese speaking were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Content analysis was used to code the transcribed interviews and develop the family-centered care model. Three major themes emerged: 1) thorough, timely, compassionate communication, 2) capacity building for families, providers, and facilities, and 3) coordination of care transitions. Participants reported valuing detailed, frequent communication that set realistic expectations and prepared them for decision making and outcomes. Areas for capacity building included strategies to increase provider cultural humility, parent participation in care, and institutional flexibility. Coordinated care transitions, including continuity of information and maintenance of partnerships with families and care teams, were highlighted. Participants who were not primarily English speaking reported particular difficulty with communication, cultural understanding, and coordinated transitions. CONCLUSIONS: This study presents a family-centered traumatic brain injury care model based on family perspectives. In addition to communication and coordination strategies, the model offers methods to address cultural and structural barriers to meeting the needs of non-English-speaking families. Given the stress experienced by families of children with traumatic brain injury, careful consideration of the model themes identified here may assist in improving overall quality of care to families of hospitalized children with traumatic brain injury. PMID- 26135065 TI - Leptin attenuates the detrimental effects of beta-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats. AB - beta-Amyloid (Abeta) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Abeta in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Abeta-induced deficits in spatial memory and in vivo hippocampal late phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1MUg) effectively alleviated Abeta1 42 (20MUg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Abeta1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Abeta induced deficits in learning and memory and the maintenance of L-LTP. PMID- 26135066 TI - Health in all policies? The case of policies to promote bicycle use in the Netherlands. PMID- 26135067 TI - Effects of modafinil on attention performance, short-term memory and executive function in university students: a randomized trial. AB - BACKGROUND: Modafinil is a drug developed and used for the treatment of excessive lethargy. Even though very effective for sleep disorders, it is still controversial whether modafinil can improve performance in high-order cognitive processes such as memory and executive function. METHODS: This randomized, double blind, placebo-controlled, crossover trial was designed to evaluate the effect of modafinil (compared to placebo) on the cognitive functions of healthy students. 160 volunteers were recruited and allocated randomly to modafinil or placebo group, and were assessed using the Stroop Test, BCET test and Digit span test. RESULTS: We found a significant difference in favor of modafinil compared to placebo in the proportion of correct answers of Stroop Test in congruent situation. A significant shorter latency of modafinil group in the incongruent situation of Stroop test was also found. No differences were found in Digit Span, or BCET tests. CONCLUSIONS: The study demonstrated that modafinil does not enhance the global cognitive performance of healthy non-sleep deprived students, except regarding non-demanding tasks. In particular, this drug does not seem to have positive effects on mental processes that sustain studying tasks in the college population under normal conditions. We expect these findings to demystify the use of this drug and help decision making concerning pharmacological public policies. PMID- 26135068 TI - Heat shock protein 70 induction by glutamine increases the alpha-synuclein degradation in SH-SY5Y neuroblastoma cells. AB - Functional defects in heat shock proteins (HSPs), e.g. Hsp70, have been reported to have a key role in Parkinson's disease (PD). Overexpressed Hsp70 re-folds aggregated alpha-synuclein to generate the non-toxic and non-aggregated form. Thus, Hsp70 is a well-defined therapeutic target, and Hsp70 promotion is an efficient strategy to prevent or even reverse the alpha-synuclein-induced toxicity in PD. The present study investigated the promotion of Hsp70 expression in SH-SY5Y neuroblastoma cells by glutamine (Gln), which has recently been recognized to induce Hsp70 expression. Furthermore, the role of heat shock factor (HSF)-1 in the Gln-mediated upregulation of Hsp70 expression was investigated. In addition, the regulatory role of Gln in alpha-synuclein degradation in alpha synuclein-overexpressing SH-SY5Y cells was determined. The results of the present study demonstrated that Gln treatment significantly upregulated Hsp70 expression at the mRNA as well as the protein level in a dose-dependent and time-dependent manner. Gln-induced Hsp70 upregulation was found to be HSF-1-dependent, as HSF-1 knockdown abrogated the Hsp70 upregulation by Gln in alpha-synuclein overexpressing SH-SY5Y cells. In conclusion, present study confirmed that Gln upregulates Hsp70 expression in SH-SY5Y neuroblastoma cells in an HSF-1-dependent manner. The upregulation of Hsp70 by Gln increases the alpha-synuclein degradation. Therefore, Gln may be a potential therapeutic agent to prevent alpha synuclein aggregation in PD. PMID- 26135069 TI - Patterned growth of single-crystal 3, 4, 9, 10-perylenetetracarboxylic dianhydride nanowire arrays for field-emission and optoelectronic devices. AB - 3, 4, 9, 10-perylenetetracarboxylic dianhydride (PTCDA) organic nanostructures possess extraordinary electronic and optoelectronic properties. However, it remains a challenge to achieve patterned growth of PTCDA nanowire (NW) arrays for integrated device applications. Here, we demonstrated the high-density, large area, uniform, and cross-aligned growth of single-crystalline PTCDA NW arrays by using Au nanoparticles (NPs) as the growth templates. The high surface energy of Au NPs led to the cross-aligned growth of organic NWs, enabling the growth of PTCDA NW arrays with any desirable patterns by pre-patterning the Au films on a Si substrate. The PTCDA NW arrays as field emitters show good performance with a large emission current density and high emission stability. Furthermore, photodetectors based on PTCDA NW arrays were constructed via a simple in-situ growth approach, which exhibited high sensitivity to a wideband light ranging from 400-800 nm and surpassed the individual NW-based photodetectors in terms of higher photocurrent and faster response speed. Successful applications of PTCDA NW arrays in field emission and photodetectors show a great potential application of organic NW arrays in future efficient electronic and optoelectronic devices. PMID- 26135070 TI - Association Between Orthopaedic Outpatient Satisfaction and Non-Modifiable Patient Factors. AB - BACKGROUND: Increasingly, patient satisfaction surveys are being utilized to evaluate hospital and physician performance. Despite this, little is known about factors associated with patient satisfaction. The objective of this study was to determine whether selected non-modifiable patient characteristics are associated with outpatient satisfaction scores. METHODS: We reviewed patient satisfaction scores from 12,177 outpatient clinical encounters at an academic orthopaedic outpatient clinic between December 2010 and October 2013. Any adult patient who completed at least one patient satisfaction survey at any point during the study period was included in this study. Factors including age, sex, employment status, type of health insurance, zip code, and orthopaedic subspecialty were recorded. Patients were divided into more satisfied and less satisfied groups, and generalized estimating equation logistic regression analysis was performed to identify factors predictive of lower patient satisfaction. RESULTS: Age was found to be strongly associated with patient satisfaction, with younger patients reporting less satisfaction; the adjusted odds ratio for the patient age of eighteen to twenty-nine years compared with the patient age of eighty years or older was 2.78 (95% confidence interval, 1.74 to 3.82) (p < 0.001). This relationship was maintained in a predictive model across all age groups, both sexes, all travel distances, and all orthopaedic subspecialties. Travel distance was also associated with patient satisfaction, with patients who live closer reporting less satisfaction compared with patients who live farther away; the adjusted odds ratio for a distance of less than fifty miles compared with a distance of fifty miles or more was 1.18 (95% confidence interval, 1.03 to 1.33) (p = 0.016). CONCLUSIONS: The finding that non-modifiable patient factors such as age and geographic location affect patient satisfaction challenges the utility of comparing patient satisfaction between populations that differ significantly with regard to such characteristics. CLINICAL RELEVANCE: A more complete knowledge of the factors that influence patient satisfaction may enable better insight into the interpretation of current patient satisfaction metrics and may allow physicians and hospitals to improve their delivery of care. PMID- 26135071 TI - The Effect of Smoking on Short-Term Complications Following Total Hip and Knee Arthroplasty. AB - BACKGROUND: Total joint arthroplasty is the most frequently performed orthopaedic procedure in the United States. The purpose of the present study was to identify differences in thirty-day morbidity and mortality following primary total hip and total knee arthroplasty according to smoking status and pack-year history of smoking. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database to identify patients who had undergone primary total hip or total knee arthroplasty between 2006 and 2012. Patients were stratified by smoking status and pack-year history of smoking. Thirty-day rates of mortality, wound complications, and total complications were compared with use of univariate and multivariate analyses. RESULTS: We identified 78,191 patients who had undergone primary total hip or total knee arthroplasty. Of these, 81.8% (63,971) were nonsmokers, 7.9% (6158) were former smokers, and 10.3% (8062) were current smokers. Current smokers had a higher rate of wound complications (1.8%) compared with former smokers and nonsmokers (1.3% and 1.1%, respectively; p < 0.001). Former smokers had a higher rate of total complications (6.9%) compared with current smokers and nonsmokers (5.9% and 5.4%, respectively; p < 0.001). Multivariate analysis identified current smokers as being at increased risk of wound complications (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.21 to 1.78), particularly deep wound infection, while both current smokers (OR, 1.18; 95% CI, 1.06 to 1.31) and former smokers (OR, 1.20; 95% CI, 1.08 to 1.34) were at increased total complication risk. Increasing pack year history of smoking resulted in increasing total complication risk. CONCLUSIONS: On the basis of our findings, current smokers have an increased risk of wound complications and both current and former smokers have an increased total complication risk following total hip or total knee arthroplasty. PMID- 26135072 TI - Effect of Different Preconditioning Protocols on Anterior Knee Laxity After ACL Reconstruction with Four Commonly Used Grafts. AB - BACKGROUND: It is currently unknown if preconditioning an anterior cruciate ligament (ACL) graft prior to fixation is helpful in eliminating possible increases in anterior knee laxity. The purpose of this study was to measure cyclic increases in anterior tibial translation of four commonly used graft tissues subjected to four preconditioning protocols. METHODS: A robotic system was used to apply 250 cycles of anteroposterior force (134 N of anterior force followed by 134 N of posterior force) to ten intact knees (ACL controls) and then to a single knee reconstructed, for separate tests, with bone-patellar tendon bone, bone-Achilles tendon, hamstring tendon, and tibialis tendon grafts following (1) no preconditioning, (2) preconditioning on a tension board (89 N of initial force held for twenty minutes), (3) preconditioning in situ (89 N of force applied to the tibial end of the graft during twenty-five flexion-extension cycles), and (4) a combination of protocols 2 and 3. RESULTS: Over the 250 cycles, all grafts were associated with a progressive increase in anterior tibial translation that was approximately an order of magnitude greater than that of the ACL, and preconditioning had no significant effect on this increase in translation. There were some significant differences in the progressive anterior tibial translation increase among the graft tissues within a given preconditioning protocol, but these differences were no greater than 1.1 mm. First-cycle and cycle-250 anterior tibial translation varied among the graft tissue types, possibly reflecting an initial "settling in" process. Regardless of the tissue type, >=75% of the total increase in the anterior tibial translation occurred within the first 125 cycles. CONCLUSIONS: Preconditioning had no significant effect on the progressive increase of anterior tibial translation from the first cycle to cycle 250 for any of the graft tissues tested. CLINICAL RELEVANCE: On the basis of these results, current preconditioning methods appear to be ineffective in reducing progressive increases in anterior knee laxity from cyclic loading. PMID- 26135073 TI - Surgical Anatomy of the Supraclavicular Brachial Plexus. AB - BACKGROUND: Brachial plexus exploration is performed in infants when addressing birth palsies and in children and adults following trauma. The upper trunk is most often injured. Traditional drawings of the brachial plexus depict the suprascapular nerve as a branch of the midportion of the upper trunk, with the more lateral branch of the upper trunk as the anterior division. We have not found this orientation to be accurate in clinical practice. The purpose of this study was to determine the branching patterns of the upper trunk and to delineate nerve orientations at the level of the divisions. METHODS: Bilateral brachial plexus dissections were performed on eight adult cadavers. The length of the upper trunk and distance of the takeoff of the suprascapular nerve from the anterior and posterior divisions was measured. The native positions of the divisions and of the suprascapular nerve from lateral to medial were recorded across all trunks. RESULTS: In six (38%) of the sixteen specimens, a trifurcation was found at the level of the upper trunk. The suprascapular nerve was the most lateral structure at the clavicular level in all specimens, followed by the posterior division and then the anterior division. The mean distance of the takeoff of the suprascapular nerve was 4 mm proximal to the branch point of the divisions; however, in two specimens, the nerve was found to take off from the posterior division proper. CONCLUSIONS: These findings differ from the standard illustrations and descriptions of the brachial plexus. A thorough understanding of the course of the upper trunk and its branches, such as the suprascapular nerve, is vital to performing nerve transfer surgery or neuroma excision and grafting. PMID- 26135074 TI - Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant. AB - BACKGROUND: Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration. METHODS: Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 MUg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing. RESULTS: Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher, respectively, in the iPTH-treated mice than in the vehicle-treated mice, and the maximum implant pullout strength was 30.9% greater. iPTH also increased osteoblast and osteoclast density by 65.2% and 47.0%, respectively, relative to the values in the vehicle group, when the data at post-implantation weeks 1 and 2 were averaged. CONCLUSIONS: iPTH increased osseointegration, cancellous mass, and the strength of the bone-implant interface. CLINICAL RELEVANCE: Our murine model is an excellent platform on which to study biological enhancement of cancellous osseointegration. PMID- 26135075 TI - Surgical Treatments of Tumor-Induced Osteomalacia Lesions in Long Bones: Seventeen Cases with More Than One Year of Follow-up. AB - BACKGROUND: Tumor-induced osteomalacia is a rare and fascinating paraneoplastic syndrome usually caused by a small, benign phosphaturic mesenchymal tumor. Most tumors are treated surgically, but we are unaware of any reports that compare the results of curettage and segmental resection for lesions in long bones. METHODS: Seventeen patients (ten male and seven female) with tumor-induced osteomalacia lesions in long bones, who underwent surgical treatment from December 2004 to August 2013 in our hospital, were included in this retrospective study. The mean follow-up (and standard deviation) was 35 +/- 27 months (range, twelve to 116 months). The characteristics of the tumor and the effects of different surgical treatments (curettage compared with segmental resection) were evaluated. RESULTS: All patients showed typical clinical characteristics of tumor-induced osteomalacia, including elevated serum fibroblast growth factor-23 (FGF-23); 82% of tumors were in the epiphysis, and 82% grew eccentrically. The mean maximum diameter of the tumors was 2.4 +/- 2.0 cm. The complete resection rates were similar for curettage (67%) and segmental resection (80%). However, the recurrence rate after curettage (50%) was higher than that after segmental resection (0%). The complete resection rate for secondary segmental resection (75%) was not different from that for primary segmental resection (83%). All of our cases of tumor-induced osteomalacia were caused by phosphaturic mesenchymal tumors. After successful removal of tumors, serum FGF-23 returned to normal within twenty-four hours and serum phosphorus levels returned to normal at a mean of 6.5 +/- 3.5 days. CONCLUSIONS: Most lesions in long bones are located in the epiphysis, so curettage is first suggested to maintain joint function. If curettage is incomplete or there is a recurrence, secondary segmental resection should be considered curative. Changes of serum FGF-23 and phosphorus levels before and after the operation may be of prognostic help. PMID- 26135076 TI - Opportunistic Osteoporosis Screening - Gleaning Additional Information from Diagnostic Wrist CT Scans. AB - BACKGROUND: Although screening for and treating osteoporosis can prevent subsequent fractures, the rates of such interventions are low following a distal radial fracture. One potential method for identifying metabolic bone disease is via Hounsfield unit (HU) measurements from diagnostic computed tomography (CT) scans. We hypothesized that HU values of the distal aspect of the radius could be used to assess local bone quality and would be predictive of distal radial fracture risk, thereby allowing the identification of patients in need of further management. METHODS: Measurements of bone mineral density (BMD) were made for 100 patients on the basis of HU values of cancellous portions of the distal aspect of the radius, the ulnar head, and the capitate. The HU values in twenty-five male and twenty-five female patients with an acute distal radial fracture documented on CT were compared with those of age and sex-matched control patients who had a CT scan obtained for other indications. RESULTS: Among the control patients, HU values decreased as age increased. When assessed on the basis of sex, both male and female patients with a distal radial fracture had significantly lower regional BMD compared with nonfracture control patients. A distal radial HU value of 218 for females and 246 for males optimized sensitivity and specificity; values below this threshold were associated with an increased risk of distal radial fracture. CONCLUSIONS: HU measurements can be obtained from any diagnostic CT scan using modern software programs and can be obtained by physicians in the office setting with minimal effort and at no additional cost or radiation exposure to the patient. Regardless of imaging indications, we suggest that patients with HU values below the identified thresholds be considered for further metabolic bone disease work-up, such as additional imaging, laboratory assessments, the initiation of osteoporosis treatment, or appropriate referral. PMID- 26135077 TI - Heterotopic Ossification: Basic-Science Principles and Clinical Correlates. AB - ? Heterotopic ossification occurs most commonly after joint arthroplasty, spinal cord injury, traumatic brain injury, blast trauma, elbow and acetabular fractures, and thermal injury.? The conversion of progenitor cells to osteogenic precursor cells as a result of cell-mediated interactions with the local tissue environment is affected by oxygen tension, pH, availability of micronutrients, and mechanical stimuli, and leads to heterotopic ossification.? Radiation and certain nonsteroidal anti-inflammatory medications are important methods of prophylaxis against heterotopic ossification.? Well-planned surgical excision can improve patient outcomes regardless of the joint involved or the initial cause of injury.? Future therapeutic strategies are focused on targeted inhibition of local factors and signaling pathways that catalyze ectopic bone formation. PMID- 26135078 TI - Does a Directive to an Internet Site Enhance the Doctor-Patient Interaction? A Prospective Randomized Study for Patients with Carpal Tunnel Syndrome. AB - BACKGROUND: Sixty-two percent of patients would like their doctor to recommend a specific web site to find health information, but only 3% of patients receive such recommendations. We investigated whether providing patients with an Internet web-site link recommended by their physician would improve patient knowledge and satisfaction. Our hypothesis was that directing patients to a reliable web site would improve both. METHODS: Sixty patients with a new diagnosis of carpal tunnel syndrome were prospectively randomized into two groups. Twenty-three patients in the control group had a traditional physician office visit and received standard care for carpal tunnel syndrome. Thirty-seven patients in the treatment group received a handout that directed them to the American Society for Surgery of the Hand (ASSH) web page on carpal tunnel syndrome in addition to the standard care provided in the office visit. Patients later completed a ten-question true-or false knowledge questionnaire and a six-item satisfaction survey. Differences in scores were analyzed using two-sample t tests. RESULTS: Less than half (48%) of the patients who were given the Internet directive reported that they had visited the recommended web site. The mean scores on the knowledge assessment (6.84 of 10 for the treatment group and 6.96 of 10 for the control group) and the satisfaction survey (4.49 of 5 for the treatment group and 4.43 of 5 for the control group) were similar for both groups. The mean score for knowledge was similar for the patients who had used the ASSH web site and for those who had not (6.89 and 6.97 respectively). Moreover, compared with patients who had not used the Internet at all to learn about carpal tunnel syndrome, patients who used the Internet scored 6.6% better (mean score, 7.14 for those who used the Internet compared with 6.70 for those who had not; p > 0.05). Regardless of Internet usage, most patients scored well on the knowledge assessment and reported a high level of satisfaction. CONCLUSIONS: Whether the patient was given a handout or had visited the ASSH or other Internet web sites, the knowledge and satisfaction scores for all patients were similar. Since the physician was the common denominator in both groups, the results indicate that the patient-physician relationship may be more valuable than the Internet in providing patient education. CLINICAL RELEVANCE: Effective communication between patients and practitioners is at the cornerstone of delivering excellent care and building trusting relationships. This study examines whether reliable Internet information should be embraced as a tool to enhance patient-surgeon communication in a clinical context. PMID- 26135079 TI - Assessing Arthroscopic Skills Using Wireless Elbow-Worn Motion Sensors. AB - BACKGROUND: Assessment of surgical skill is a critical component of surgical training. Approaches to assessment remain predominantly subjective, although more objective measures such as Global Rating Scales are in use. This study aimed to validate the use of elbow-worn, wireless, miniaturized motion sensors to assess the technical skill of trainees performing arthroscopic procedures in a simulated environment. METHODS: Thirty participants were divided into three groups on the basis of their surgical experience: novices (n = 15), intermediates (n = 10), and experts (n = 5). All participants performed three standardized tasks on an arthroscopic virtual reality simulator while wearing wireless wrist and elbow motion sensors. Video output was recorded and a validated Global Rating Scale was used to assess performance; dexterity metrics were recorded from the simulator. Finally, live motion data were recorded via Bluetooth from the wireless wrist and elbow motion sensors and custom algorithms produced an arthroscopic performance score. RESULTS: Construct validity was demonstrated for all tasks, with Global Rating Scale scores and virtual reality output metrics showing significant differences between novices, intermediates, and experts (p < 0.001). The correlation of the virtual reality path length to the number of hand movements calculated from the wireless sensors was very high (p < 0.001). A comparison of the arthroscopic performance score levels with virtual reality output metrics also showed highly significant differences (p < 0.01). Comparisons of the arthroscopic performance score levels with the Global Rating Scale scores showed strong and highly significant correlations (p < 0.001) for both sensor locations, but those of the elbow-worn sensors were stronger and more significant (p < 0.001) than those of the wrist-worn sensors. CONCLUSIONS: A new wireless assessment of surgical performance system for objective assessment of surgical skills has proven valid for assessing arthroscopic skills. The elbow-worn sensors were shown to achieve an accurate assessment of surgical dexterity and performance. CLINICAL RELEVANCE: The validation of an entirely objective assessment of arthroscopic skill with wireless elbow-worn motion sensors introduces, for the first time, a feasible assessment system for the live operating theater with the added potential to be applied to other surgical and interventional specialties. PMID- 26135080 TI - Where There Is Smoke, There Is Fire! Commentary on an article by Kyle R. Duchman, MD, et al.: "The Effect of Smoking on Short-Term Complications Following Total Hip and Knee Arthroplasty". PMID- 26135081 TI - Exaggerated perception of facial expressions is increased in individuals with schizotypal traits. AB - Emotional facial expressions are indispensable communicative tools, and social interactions involving facial expressions are impaired in some psychiatric disorders. Recent studies revealed that the perception of dynamic facial expressions was exaggerated in normal participants, and this exaggerated perception is weakened in autism spectrum disorder (ASD). Based on the notion that ASD and schizophrenia spectrum disorder are at two extremes of the continuum with respect to social impairment, we hypothesized that schizophrenic characteristics would strengthen the exaggerated perception of dynamic facial expressions. To test this hypothesis, we investigated the relationship between the perception of facial expressions and schizotypal traits in a normal population. We presented dynamic and static facial expressions, and asked participants to change an emotional face display to match the perceived final image. The presence of schizotypal traits was positively correlated with the degree of exaggeration for dynamic, as well as static, facial expressions. Among its subscales, the paranoia trait was positively correlated with the exaggerated perception of facial expressions. These results suggest that schizotypal traits, specifically the tendency to over-attribute mental states to others, exaggerate the perception of emotional facial expressions. PMID- 26135082 TI - [Innovative Approaches for Next-generation Biodrugs Development]. PMID- 26135083 TI - [Development of New Biologics through Creation of a Functional Cytokine Mutant]. AB - The clinical use of cytokines is fairly limited because of their characteristics of having significant bioactivity and low stability, although some are useful biopharmaceuticals, such as interferon. Cytokines, which are secreted from various immune cells, show many kinds of bioactivities including unexpected activities; thus it would be desirable to regulate cytokine activity. Recently, we have developed a new drug delivery system (DDS) to create structural mutant cytokines using a phage display system. This system can produce functional mutant proteins that can bind their objective targets specifically. In this study, tumor necrosis factor (TNF) was used as a model cytokine to create agonist and antagonist activities against two TNF receptors TNFR1 and TNFR2, respectively. We created a phage library expressing mutant TNF, where the amino acids in the binding interface between TNF and TNF receptors were alternately exchanged. Affinity panning was performed at the optimum condition and the bioactivities of these mutant TNFs were analyzed to obtain the objective agonists or antagonists. The pharmacological activity and toxicity of these engineered TNF mutants could indicate their potential use as novel biopharmaceutical agents. PMID- 26135084 TI - [Functionalization of Bispecific Therapeutic Antibodies Based on Protein Engineering]. AB - Although antibodies have been used as molecularly targeted agents for difficult to-treat diseases such as cancers, the high production costs associated with mammalian expression systems continue to be a drawback. In addition, the clinical efficacy of conventional IgG antibodies is limited. Several types of recombinant antibody (e.g. fused with anticancer drugs, multivalent, or multispecific) have been designed in efforts to develop next-generation antibodies with higher functionality. We used protein engineering to construct several anticancer recombinant antibodies by developing bispecific antibodies that induced specific antitumor effects against cancer cells through the recruitment of lymphocytes. We found that a humanized small bispecific antibody (Ex3) that targets epidermal growth factor receptor on tumor cells and CD3 on T lymphocytes had marked anticancer activity. Furthermore, the function of Ex3 was enhanced by fusion with the human Fc region, domain rearrangement, multimerization, and affinity maturation; a combination of these modifications showed at least additive cytotoxic effects. Interestingly, merely rearranging the domain order of Ex3 induced substantial cytotoxic enhancements, even though the structural format remained the same. Here, we describe our efforts to develop highly functional bispecific antibodies as next-generation therapeutic antibodies using protein engineering. PMID- 26135085 TI - [Nonclinical Evaluation of Next-generation Therapeutic Monoclonal Antibodies]. AB - Therapeutic monoclonal antibodies (mAbs) exert their effects via binding to specific target molecules, which is expected to show rare off-target adverse reactions. However, nonclinical evaluation of mAbs is difficult because they often lack reactivity toward orthologous targets in animals. During the nonclinical evaluation of mAbs, not only the target molecules but fragment crystallizable (Fc) receptors, which regulate the immune effector functions and pharmacokinetic properties of mAbs, should be considered. In this review, factors for extrapolating nonclinical study results to clinical settings are discussed by focusing on Fc receptors. The human Fcgamma receptor family consists of FcgammaRI, IIa, IIb, IIIa, and IIIb; Fcgamma receptors in laboratory animals are structurally and functionally different from those in humans. In addition, interactions between human IgG-Fc, a component of therapeutic mAbs, and animal Fcgamma receptors are still not fully understood. With regard to neonatal Fc receptor (FcRn), related molecules comprising the FcRn family are not known; however, critical amino acid residues involved in IgG binding are different between human and mouse. In case of next-generation mAbs with a novel structure or mode of action, knowledge from related drugs is limited. To ensure safety of next-generation mAbs, a thorough understanding of the differences in Fc receptors among species and the interactions between mAbs and Fc receptors is required, and the appropriateness of the nonclinical study design should be carefully examined prior to conducting clinical studies. PMID- 26135086 TI - [Sugar Chain Construction of Functional Natural Products Using Plant Glucosyltransferases]. AB - Plant secondary product glycosyltransferases belong to family 1 of the glycosyltransferase superfamily and mediate the transfer of a glycosyl residue from activated nucleotide sugars to lipophilic small molecules, thus affecting the solubility, stability and pharmacological activities of the sugar-accepting compounds. The biotechnological application of plant glycosyltransferases in glycoside synthesis has attracted attention because enzymatic glycosylation offers several advantages over chemical methods, including (1) avoiding the use of harsh conditions and toxic catalysts, (2) providing strict control of regio and stereo-selectivity and (3) high efficiency. This review describes the in vivo and in vitro glycosylation of natural organic compounds using glycosyltransferases, focusing on our investigation of enzymatic synthesis of curcumin glycosides. Our current efforts toward functional characterization of some glycosyltransferases involved in the biosynthesis of iridoids and crocin, as well as in the sugar chain elongation of quercetin glucosides, are described. Finally, I describe the relationship of the structure of sugar chains and the intestinal absorption which was investigated using chemoenzymatically synthesized quercetin glycosides. PMID- 26135087 TI - [Vacuolar H(+)-ATPase and the Secondary Transporters: Their Identification, Mechanism, Function and Physiological Relevance]. AB - Eukaryotic cells possess acidic compartments with pH ranging from 0.1-6.5. Studies in the last couple of decades indicated that the acid pool is established by vacuolar proton ATPase, and is essential for various physiological and pathological processes. I have identified the vacuolar ATPase as well as several secondary transporters which are energetically coupled with vacuolar ATPase. I have also established the protocol for analysis of the structure and function of transporter proteins applicable to essentially all known transporters. In this article, I am going to summarize this study and describe some topics. PMID- 26135088 TI - [Development and Validation of Estimate Equations for Adverse Drug Reactions Using Risk Factors and Subjective Symptoms]. AB - The purpose of this study was to develop and validate estimate equations for preventing adverse drug reactions (ADRs). We conducted five case-control studies to identify individual risk factors and subjective symptoms associated with the following five ADRs: drug-induced ischemic heart disease; renal damage; muscle disorder; interstitial pneumonia; and leucopenia. We performed logistic regression analysis and obtained eight regression equations for each ADR. We converted these to ADR estimate equations for predicting the likelihood of ADRs. We randomly selected 50 cases with non-individual ADRs from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 65000 case reports of ADRs, and assigned these cases to a validation case group. We then calculated the predictive probability for 50 cases using the eight estimate equations for each ADR. The highest probability for each ADR was set as the probability of each ADR. If the probability was over 50%, the case was interpreted as ADR-positive. We calculated and evaluated the sensitivity, specificity, and positive likelihood ratio of this system. Sensitivity of the estimate equations for muscle disorder and interstitial pneumonia were >=90%. Specificity and positive likelihood ratios of estimate equations for renal damage, interstitial pneumonia and leucopenia were >=80% and >=5, respectively. Our estimate equations thus showed high validity, and are therefore helpful for the prevention or early detection of ADRs. PMID- 26135090 TI - Foreword. PMID- 26135089 TI - Management of IBD in the Elderly Patient With Cancer. AB - OPINION STATEMENT: The management of inflammatory bowel disease (IBD) in patients with known or recently treated cancer has become a common dilemma in our ageing population. Older patients are commonly excluded from prospective trials, and co morbid status and polypharmacy may muddy our understanding of the impact of therapies on these patients. Immunosuppression (anti-TNF therapy, antimetabolite therapy) carries a relative contra-indication in the setting of known cancer as it is expected to increase cancer risk and increase propagation of in situ cancer. Recent studies have sought to investigate this risk by looking from two sides-the impact of cancer therapies on IBD outcomes and the risk of cancer occurrence/recurrence in patients on IBD therapies. In this chapter, we review this data and determine the safety of commonly used IBD therapies in this potentially vulnerable elderly population. PMID- 26135091 TI - Is there a role for stenting in case of acute esophageal variceal bleeding? PMID- 26135092 TI - Enteroscopy in small-bowel Crohn's disease (CD): hypes and hopes. PMID- 26135093 TI - Impact of balloon-assisted enteroscopy on the diagnosis and management of suspected and established small-bowel Crohn's disease. AB - BACKGROUND AND AIMS: The role of recently developed balloon-assisted enteroscopy (BAE) in small-bowel Crohn's disease (CD) is not well established. The purpose of this study is to determine the clinical impact of BAE on patients with suspected and established small-bowel CD. METHODS: This study included 22 patients (group A) with suspected small-bowel CD and 43 patients (group B) with established small bowel CD with or without previous surgery, who underwent BAE, in a prospective BAE registry of a US academic medical institution. All underwent abdominal imaging studies including computed tomography (CT) or magnetic resonance (MR) enterography before BAE. The main outcome measurements were diagnostic yield and clinical outcomes. RESULTS: In total, 78 BAE procedures were carried out in 65 patients. In group A (n = 22, 25 BAE procedures), enteroscopy led to a diagnosis of CD in six patients (27.3 %). Non-steroidal anti-inflammatory drug-related enteropathy was diagnosed in three patients (13.6 %), whereas no lesions were found in the remaining 13 patients. In group B (n = 43, 53 BAE procedures) enteroscopy revealed active intestinal inflammation with ulcers and/or luminal stenosis in 18 patients (41.9 %), which led to a change and escalation of medical therapy. Five patients without active ulcers underwent successful dilation of small-bowel strictures with resulting resolution of obstructive symptoms. Of the 78 BAE procedures, two patients (2.6 %) had bleeding complications which were successfully treated conservatively. One patient (1.3 %) underwent surgery due to procedure-related perforation. CONCLUSIONS: The use of BAE may help improve management in patients with suspected and established small-bowel CD. PMID- 26135094 TI - Endoscopic mucosal resection or ablation for Barrett's esophagus containing high grade dysplasia: agreement strongest among expert gastroenterologists. AB - BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) plays an important role in the staging of Barrett's esophagus (BE) and the evaluation of high grade dysplasia (HGD). The study aim is to assess the interobserver agreement among gastroenterologists expert in BE endotherapy, gastroenterologists without specified expertise in BE endotherapy, and gastroenterology trainees in recommending EMR vs ablation for BE HGD lesions, and to assess the effect of a one-time educational intervention on the interobserver agreement among non experts and trainees. PATIENTS AND METHODS: An electronic survey containing 30 still endoscopic images of BE HGD was sent to three groups of respondents: experts, non-experts, and trainees. Respondents were asked to select "Endoscopic Mucosal Resection" or "Ablation" as the most appropriate next step in management. Non-experts and trainees were then invited to repeat the survey following an educational intervention. The main outcome measure was interobserver agreement measured by Fleiss' Kappa statistic and percent agreement. RESULTS: In selecting between EMR and ablation, on the pre-intervention survey there was the highest amount of agreement among experts (kappa = 0.437), followed by agreement among trainees (kappa = 0.281), and non-experts (kappa = 0.107). Experts demonstrated significantly higher agreement compared to either trainees (P < 0.001) or non experts (P < 0.001). On the post-intervention survey, interobserver agreement remained low among both trainees (kappa = 0.20) and non-experts (kappa = 0.14). Comparing the results of the surveys, there was no evidence that agreement differed for either trainees or non-experts. CONCLUSIONS: Future efforts are needed to enable endoscopist recognition of BE HGD lesions. Consensus guidelines alone are insufficient in directing preferred endoscopic management of BE HGD. PMID- 26135095 TI - Effect of novel bright image enhanced endoscopy using blue laser imaging (BLI). AB - BACKGROUND AND STUDY AIMS: The novel method of image-enhanced endoscopy (IEE) named blue laser imaging (BLI) can enhance the contrast of surface vessels using lasers for light illumination. BLI has two IEE modes: high contrast mode (BLI contrast) for use with magnification, and bright mode (BLI-bright), which achieves a brighter image than BLI-contrast and yet maintains the enhanced visualization of vascular contrast that is expected for the detection of tumors from a far field of view. The aim of this study is to clarify the effect of BLI bright with a far field of view compared to BLI-contrast and commonly available narrow-band imaging (NBI). PATIENTS AND METHODS: Patients with neoplasia, including early cancer in the pharynx, esophagus, stomach, or colorectum, were recruited and underwent tandem endoscopy with BLI and NBI systems. Six sets of images of the lesions were captured with a changing observable distance from 3 to 40 mm. Individual sets of images taken from various observable distances were assessed for visibility among BLI-bright, BLI-contrast, and NBI modes. The brightness and contrast of these images were also analyzed quantitatively. RESULTS: Of 51 patients, 39 were assessed. Image analysis indicated that only BLI bright maintained adequate brightness and contrast up to 40 mm and had significantly longer observable distances compared to the other methods. Furthermore, BLI-bright enhanced the visualization of serious lesions infiltrating into deeper layers, such as esophageal lamina propria or gastric submucosal cancers. CONCLUSIONS: BLI-bright will be a helpful tool for the far field view with IEE in organs with wider internal spaces such as the stomach. PMID- 26135096 TI - Endoscopic ultrasound-guided fine-needle aspiration with on-site cytopathology versus core biopsy: a comparison of both techniques performed at the same endoscopic session. AB - BACKGROUND: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) with bedside cytopathology is the gold standard for assessment of pancreatic, subepithelial, and other lesions in close proximity to the gastrointestinal tract, but it is time-consuming, has certain diagnostic limitations, and bedside cytopathology is not widely available. AIMS: The goal of this study is to compare the diagnostic yield of EUS-guided FNA with on-site cytopathology and EUS-guided core biopsy. METHODS: Twenty-six patients with gastrointestinal mass lesions requiring biopsy at a tertiary medical center were included in this retrospective analysis of a prospective cohort. Two core biopsies were taken using a 22 gauge needle followed by FNA guided by a bedside cytopathologist at the same endoscopic session. The diagnostic yield and test characteristics of EUS core biopsy and EUS FNA with bedside cytopathology were examined. RESULTS: The mean number of passes was 3.2 for FNA, and the mean procedure time was 39.4 minutes. The final diagnosis was malignant in 92.3 %. Sensitivity and specificity were 83 % and 100 %, respectively, for FNA, and 91.7 % and 100 %, respectively, for core biopsy. Diagnostic accuracy was 92.3 % for FNA and 84.6 % for core biopsy. The two approaches were in agreement in 88.4 % with a kappa statistic of 0.66 (95 % confidence interval 0.33 - 0.99). CONCLUSIONS: An approach using two passes with a core biopsy needle is comparable to the current gold standard of FNA with bedside cytopathology. The performance of two core biopsies is time-efficient and could represent a good alternative to FNA with bedside cytopathology. PMID- 26135097 TI - Endoscopic treatment of large pancreatic fluid collections (PFC) using self expanding metallic stents (SEMS) - a two-center experience. AB - Background/study aim: During the last several years, endoscopic ultrasound (EUS) guided pancreatic fluid collections' (PFC) drainage has evolved into the preferred drainage technique. Recently, self-expanding metallic stents (SEMS) have been used as an alternative to double pigtail stents, with the advantage of providing a larger diameter fistula, thereby decreasing the risk of early obstruction and also allowing for direct endoscopic exploration of the cavity. The aim of this study was to evaluate the technical and clinical success, safety, and outcome of patients undergoing EUS-guided drainage of complex PFC using SEMS. PATIENTS/MATERIALS AND METHODS: The study was conducted at two tertiary hospitals from January 2010 to January 2013. All patients with PFC referred for endoscopic drainage were enrolled in a prospective database. The inclusion criteria were: (1) patients with pseudocysts or walled-off necrosis based on the revised Atlanta classification; (2) symptomatic patients with thick PFC; (3) PFC that persisted more than 6 weeks; and (4) large PFC diameter (>= 9 cm). The exclusion criteria consisted of coagulation disorders, PFC bleeding or infection, and failure-to inform written consent. RESULTS: A total of 16 patients (9 females, 7 males; mean age 52.6, range 20 - 82) underwent EUS drainage with SEMS. There were 14 cases of pseudocysts and 2 cases of walled-off necrosis. The etiologies of the PFC were mainly gallstones (8 of 16 patients, 50 %) and alcohol (5 of 16 patients, 31 %). Technical success was achieved in 100 % of the cases. All patients had a complete resolution of the PFC. CONCLUSION: Transmural EUS-guided drainage of complex PFC using SEMS is feasible, appears safe, and is efficacious. However, the exchange of the UC (uncovered)-SEMS for plastic stents is mandatory within 1 week. Future prospective studies, preferably multicenter studies, comparing SEMS versus traditional plastic stents for the drainage of PFC are warranted. PMID- 26135098 TI - Polyethylene glycol vs sodium picosulfate/magnesium citrate for colonoscopy preparation. AB - BACKGROUND AND STUDY AIMS: Polyethylene glycol-based electrolyte solutions (PEG ELS) and the combination of sodium picosulfate/magnesium citrate (SPMC) are commonly used bowel preparation agents. The aim of the present study was to compare the two agents with regard to cleansing efficacy and tolerance among individuals scheduled for outpatient colonoscopy. MATERIALS AND METHODS: The 368 colonoscopy outpatients at three Norwegian hospitals were randomized to bowel lavage with either PEG-ELS or SPMC. Compliance and patient tolerance were evaluated using a patient questionnaire. Bowel cleansing was evaluated using the Ottawa Bowel Preparation Quality Scale (OBPS), a validated scoring system with scores between 0 (best) and 14. RESULTS: There was no difference in the cleansing quality between the PEG-ELS and SPMC groups (median OBPS 5.0 in both groups). The group that received SPMC reported better overall patient tolerance than the PEG ELS group (72.6 % vs 59.0 % reporting no or slight discomfort, P < 0.01). Compliance with the recommended total fluid intake (4 L) was better in the SPMC group than in the PEG-ELS group (94.2 % vs 81.2 % respectively, P < 0.01); moreover, the polyp detection rate was superior (34.3 % vs 23.3 %, P = 0.02). CONCLUSION: PEG-ELS and SPMC are equally effective in cleansing efficacy, but SPMC was better tolerated by patients and resulted in superior patient compliance and polyp detection rate. CLINICAL TRIAL REGISTRATION: NCT01624454. PMID- 26135099 TI - Factors predicting clinical outcomes of endoscopic submucosal dissection in the rectum and sigmoid colon during the learning curve. AB - BACKGROUND AND STUDY AIMS: Colorectal endoscopic submucosal dissection (ESD) is associated with significant technical difficulty, long procedure time, and increased risk of complications, especially perforation. This study aimed to determine the factors associated with clinical results of ESD during the learning curve. PATIENTS AND METHODS: In total, 44 patients with sessile and flat rectal and sigmoid colon lesions underwent ESD from November 2009 to September 2013. The procedure time, resection method, tumor size, location, gross morphology, presence of fibrosis, histologic findings, rates of en bloc and piecemeal resections and perforation were analyzed. The ESD procedure was classified as technically difficult in the case of procedure time > 120 minutes and/or piecemeal resection. The whole study time was divided into two periods: first period: resections 1 - 22, second period: resections 23 - 44. RESULTS: En bloc and R0 resection have been achieved in 84.1 % of lesions. The mean procedure time was 119.95 +/- 11.22 minutes (range 25 - 360 minutes). Perforation was seen in five cases (11.4 %). A larger tumor size was a risk factor for difficult ESD (P = 0.0001). A finding of fibrosis was a risk factor for piecemeal ESD (P = 0.0074), and perforation (P = 0.0012). There was a high direct positive correlation between tumor size and operation time (r = 0.83, P < 0.0001, 0.95 and 0.99 confidence interval for rho 0.71 - 0.904). There was no significant difference between the first and second period in terms of mean procedure time, en bloc resection or complication rate. CONCLUSION: A larger tumor size was associated with technically difficult ESD. Severe submucosal fibrosis was a risk factor for both piecemeal resection and perforation. PMID- 26135100 TI - Preliminary colonoscopy facilitates retrograde double-balloon enteroscopy. AB - BACKGROUND AND STUDY AIMS: Retrograde double-balloon enteroscopy (RDBE) has a high failure rate due to difficulty intubating the ileo-cecal (IC) valve. We examined the utility of a pre-RDBE colonoscopy using a pediatric colonoscope to clean the cecum and perform an initial intubation of the IC valve. PATIENTS AND METHODS: This study is a retrospective review of RDBE procedures for 45 patients at a single tertiary-care center to examine the success of IC intubation, maximal depth of enteroscope insertion, and duration of the procedure. RESULTS: The IC intubation success rate among patients who underwent RDBE using this novel method was 100 % as compared to 72.7 % using the traditional method (P < 0.003). CONCLUSIONS: RDBE preceded by colonoscopy had a significantly higher IC intubation success rate, compared to RDBEs performed using the traditional method. RESULTS support the use of this novel method when IC valve intubation using standard methods is difficult, and it may limit the need for repeat procedures or the use of other modalities for examining the small bowel. PMID- 26135101 TI - Self-Expanding Metal Stent (SEMS): an innovative rescue therapy for refractory acute variceal bleeding. AB - BACKGROUND: Acute variceal bleeding (AVB) is a life-threatening complication of liver cirrhosis or less commonly splenic vein thrombosis. Pharmacological and endoscopic interventions are cornerstones in the management of variceal bleeding but may fail in 10 - 15 % of patients. Rescue therapy with balloon tamponade (BT) or transjugular intrahepatic portosystemic shunt (TIPS) may be required to control refractory acute variceal bleeding effectively but with some limitations. The self-expanding metal stent (SEMS) is a covered, removable tool that can be deployed in the lower esophagus under endoscopic guidance as a rescue therapy to achieve hemostasis for refractory AVB. AIMS: To evaluate the technical feasibility, efficacy, and safety of SEMS as a rescue therapy for AVB. METHODS: In this review article, we have performed an extensive literature search summarizing case reports and case series describing SEMS as a rescue therapy for AVB. Indications, features, technique, deployment, success rate, limitations, and complications are discussed. RESULTS: At present, 103 cases have been described in the literature. Studies have reported 97.08 % technical success rates in deployment of SEMS. Most of the stents were intact for 4 - 14 days with no major complications reported. Stent extraction had a success rate of 100 %. Successful hemostasis was achieved in 96 % of cases with only 3.12 % found to have rebleeding after placement of SEMS. Stent migration, which was the most common complication, was observed in 21 % of patients. CONCLUSION: SEMS is a safe and effective alternative approach as a rescue therapy for refractory AVB. PMID- 26135102 TI - Quality of colonoscopy in Lynch syndrome. AB - Lynch syndrome (LS) accounts for 2 - 4 % of all colorectal cancers. Affected family members have a germline mutation in one of the DNA mismatch repair genes MLH1, PMS2, MSH2, or MSH6, and a lifetime risk for development of colorectal cancer of 25 - 75 %. Current guidelines recommend annual to biannual surveillance colonoscopy in mutation carriers. Several factors may predict failure to prevent interval cancer in LS: more lesions in the right colon; more flat ("non polypoid") and lateral growing polyps; small adenomas may already harbor high grade dysplasia or a high percentage of villous component and become advanced adenomas; there is a short duration of the adenoma - carcinoma sequence; synchronous lesions have high prevalence; patients are younger and less tolerant to colonoscopy (need more sedation); and repeated colonoscopies are needed for lifelong surveillance (patient experience is important for compliance). In order to prevent cancer in LS patients, surveillance colonoscopy should be performed in an endoscopic unit experienced with LS, every 1 - 2 years, starting at age 20 - 25 years, or 10 years younger than the age of first diagnosis in the family (whichever is first), and yearly after the age of 40 years. Colonoscopy in LS patients should be a very meticulous and precise procedure (i. e. taking sufficient withdrawal time, documentation of such warranted), with removal of all of the polyps, special attention to the right colon and alertness to flat lesions. Following quality indicators such as successful cleansing of the colon and removal of every polyp will probably improve prevention of interval cancers. At this moment, none of the new endoscopic techniques have shown convincing superiority over conventional high resolution white light colonoscopy. PMID- 26135103 TI - Endoscopic ultrasound-guided ethanol ablation of a large metastatic carcinoid tumor: success with a note of caution. AB - Endoscopic ultrasonography with fine needle infusion (EUS-FNI) of alcohol is the most reported method for EUS-guided tumor ablation. Several studies have reported successful EUS-guided ablation of pancreatic neuroendocrine tumors. However, these tumors have been relatively small (< 3 cm). In this report, a 50-year-old man with a metastatic carcinoid tumor with a large porta hepatis mass was referred to our clinic for EUS-guided ethanol ablation. After two separate EUS FNI ablations, there was a 36 % reduction in tumor size (9.0 * 11.4 cm to 6.7 * 9.8 cm) with associated tumor lysis syndrome. Chromogranin A levels decreased from 460 to 132 ng/mL. The patient reported complete resolution of abdominal pain within 2 weeks, but only mild improvement in flushing and diarrhea. In conclusion, large metastatic neuroendocrine tumors can be successfully treated with EUS-guided ethanol ablation. Evidence-based guidelines are needed with regard to the appropriate volume of ethanol injected in EUS-guided ablation to promote the efficacy and safety of this emerging procedure. PMID- 26135104 TI - Idiopathic granulomatous gastritis diagnosed with endoscopic ultrasound-guided fine-needle aspiration: report of a case. AB - A 71-year-old man in whom a gastric submucosal lesion was found incidentally was referred to our hospital for detailed examination. Esophagastroduodenoscopy showed a submucosal lesion in the body of the stomach. Endoscopic ultrasound revealed a 15-mm hypoechoic round mass with calcifications arising from the muscular layer. Confusing the diagnosis, it resembled a gastrointestinal mesenchymal tumor. Subsequently, endoscopic ultrasound-guided fine-needle aspiration was conducted for definitive diagnosis. Pathologic analysis showed a granuloma. Because this patient had no prior exposure to tuberculosis or Helicobacter pylori infection and had no abnormal laboratory data, this submucosal lesion was diagnosed as idiopathic granulomatous gastritis. PMID- 26135105 TI - An unusual cause of ankle swelling. PMID- 26135106 TI - Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage. AB - The dual targeting of PI3K-AKT-mTOR and Ras-Raf-MEK-ERK pathways is a potential anticancer therapy, but unfortunately, the response rate has been low in early phase clinical trials. Pre-clinical models have suggested that an apoptotic response to dual PI3K and MEK targeting is relatively rare and understanding apoptotic avoidance could lead to increased clinical efficiency. This study investigated solid cancer cell lines, which are known to be sensitive to dual PI3K and MEK inhibition but to have a limited apoptotic response. The cells were exposed to dual PI3K and MEK blockage in combination with a panel of additional pharmacological agents and cytotoxicity and apoptosis were analyzed. Our results indicated that the BH3 mimetic ABT-263, the HDAC inhibitor entinostat and the multikinase inhibitor dasatinib increased the cytotoxicity and apoptotic response of dual PI3K and MEK targeting. Furthermore, ABT-263 and entinostat was able to induce apoptosis in combination with single agent PI3K and MEK inhibitors. Protein expression, immunoprecipitation and siRNA knockdown models suggested that Bcl-xl and Mcl-1 were the most important factors circumventing PI3K and/or MEK inhibition-mediated apoptosis. The results suggest that the cytotoxicity of PI3K and/or MEK inhibitor treatments can be augmented by combinatory approaches targeting anti-apoptotic mediators Bcl-xl and Mcl-1. PMID- 26135107 TI - Lentinula edodes-derived polysaccharide rejuvenates mice in terms of immune responses and gut microbiota. AB - Aging is characterized by impaired immunity and unbalanced gut microbiota. Prebiotics have the capability to prevent or reverse age-related declines in health by modulating gut microbiota. Mushroom polysaccharides have been suggested to be potential prebiotics. However, their effects on the immunity and gut microbiota in aged mice have not been determined. This study firstly assessed the effects of a heteropolysaccharide L2 isolated from the fruit body of L. edodes on the immune response of aged mice, and then compared the composition of fecal microbiota in adult (N), old (O) and L2-treated old (Oa) mice using the high throughput pyrosequencing technique. The results showed that L2 can restore the age-attenuated immune responses by increasing cytokine levels in peripheral blood. Moreover, L2 can partly reverse the age-altered composition of gut microbiota. The Euclidean distances (De) among 3 groups (N, O and Oa) are determined to be De(O, N) = 0.19, De(O, Oa) = 0.20, and De(N, Oa) = 0.10, i.e. there is a marked reduction in the distance from 0.19 to 0.1 by L2. This suggests the beneficial effects of L2 on enhancing immunity and improving gut health. PMID- 26135108 TI - Optimal Target Region for Subject Classification on the Basis of Amyloid PET Images. AB - Classification of subjects on the basis of amyloid PET scans is increasingly being used in research studies and clinical practice. Although qualitative, visual assessment is currently the gold standard approach, automated classification techniques are inherently more reproducible and efficient. The objective of this work was to develop a statistical approach for the automated classification of subjects with different levels of cognitive impairment into a group with low amyloid levels (AbetaL) and a group with high amyloid levels (AbetaH) through the use of amyloid PET data from the Alzheimer Disease Neuroimaging Initiative study. METHODS: In our framework, an iterative, voxelwise, regularized discriminant analysis is combined with a receiver operating characteristic approach that optimizes the selection of a region of interest (ROI) and a cutoff value for the automated classification of subjects into the AbetaL and AbetaH groups. The robustness, spatial stability, and generalization of the resulting target ROIs were evaluated by use of the standardized uptake value ratio for (18)F-florbetapir PET images from subjects who served as healthy controls, subjects who had mild cognitive impairment, and subjects who had Alzheimer disease and were participating in the Alzheimer Disease Neuroimaging Initiative study. RESULTS: We determined that several iterations of the discriminant analysis improved the classification of subjects into the AbetaL and AbetaH groups. We found that an ROI consisting of the posterior cingulate cortex/precuneus and the medial frontal cortex yielded optimal group separation and showed good stability across different reference regions and cognitive cohorts. A key step in this process was the automated determination of the cutoff value for group separation, which was dependent on the reference region used for the standardized uptake value ratio calculation and which was shown to have a relatively narrow range across subject groups. CONCLUSION: We developed a data-driven approach for the determination of an optimal target ROI and an associated cutoff value for the separation of subjects into the AbetaL and AbetaH groups. Future work should include the application of this process to other datasets to facilitate the determination of the translatability of the optimal ROI obtained in this study to other populations. Ideally, the accuracy of our target ROI and cutoff value could be further validated with PET-autopsy data from large-scale studies. It is anticipated that this approach will be extremely useful for the enrichment of study populations in clinical trials involving putative disease-modifying therapeutic agents for Alzheimer disease. PMID- 26135109 TI - Relationship Between 18F-FDG PET/CT Scans and KRAS Mutations in Metastatic Colorectal Cancer. AB - Several studies have shown that KRAS mutations in colorectal cancer (CRC) result in the lack of response to anti-epidermal growth factor receptor-based therapy; thus, KRAS mutational testing has been incorporated into routine clinical practice. However, 1 limitation of this test is the heterogeneity of KRAS status, which can be either intratumoral heterogeneity within an individual primary CRC or discordant KRAS status between a primary CRC and its corresponding metastases. We previously reported that (18)F-FDG accumulation was significantly higher in primary CRCs with mutated KRAS than in those with wild-type KRAS. However, the clinical utility of the previous report has been limited because endoscopic biopsy for testing KRAS status is safe and feasible only in primary CRC. The purpose of this study was to investigate whether KRAS status is associated with (18)F-FDG accumulation in metastatic CRC and whether (18)F-FDG PET/CT scans can be used to predict the KRAS status of metastatic CRC. METHODS: A retrospective analysis was performed on 55 metastatic CRC tumors that were identified by (18)F FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax) of the respective metastatic tumor was calculated from (18)F-FDG accumulation. RESULTS: From the analysis with the 55 tumors, no significant correlation was found between SUVmax and KRAS status. We next analyzed only tumors larger than 10 mm to minimize the bias of partial-volume effect and found that SUVmax was significantly higher in the KRAS-mutated group than in the wild-type group (8.3 +/- 4.1 vs. 5.7 +/- 2.4, respectively; P = 0.03). Multivariate analysis indicated that SUVmax remained significantly associated with KRAS mutations (P = 0.04). KRAS status could be predicted with an accuracy of 71.4% when an SUVmax cutoff value of 6.0 was used. CONCLUSION: (18)F-FDG accumulation into metastatic CRC was associated with KRAS status. (18)F-FDG PET/CT scans may be useful for predicting the KRAS status of metastatic CRC and help in determining the therapeutic strategies against metastatic CRC. PMID- 26135110 TI - Pulmonary Scintigraphy for the Diagnosis of Acute Pulmonary Embolism: A Survey of Current Practices in Australia, Canada, and France. AB - There are currently no data published regarding the proportion of nuclear medicine centers using SPECT or SPECT/CT rather than planar ventilation/perfusion (V/Q) imaging in patients with suspected acute pulmonary embolism (PE). Furthermore, the reporting criteria used for interpretation of both planar and SPECT V/Q scans are variable and data are lacking regarding which criteria are commonly used in various centers. The aim of this study was to assess current practices regarding the performance and interpretation of lung scintigraphy across 3 different countries. METHODS: A short online survey composed of simple multiple-choice questions was distributed to nuclear medicine departments in Australia, Canada, and France during the period April to December 2014. The survey covered image acquisition, interpretation criteria for SPECT and planar images, and use of pseudoplanar images and radiopharmaceuticals. Information was initially solicited by 2 sets of e-mails, which pointed to the survey internet link. Departments were subsequently contacted by telephone. A single response per department was consolidated. RESULTS: Three hundred thirty-one responses were collected (Australia, 74; Canada, 48; and France, 209). Twenty-eight percent of centers indicated use of V/Q planar imaging alone whereas 72% of centers included some form of SPECT in their acquisition protocol for evaluation of PE, specifically V/Q SPECT in 36%, V/Q SPECT/CT in 29%, Q SPECT/CT in 2%, and both V/Q planar and SPECT in 5%, with a strong variability among countries. The most commonly used criteria for SPECT interpretation were the those of the European Association of Nuclear Medicine (60%). Criteria used for planar interpretation were heterogeneous (European Association of Nuclear Medicine criteria, 35%; Prospective Investigation of Pulmonary Embolism Diagnosis study, 29%; no standardized criteria, 21%). Sixty-three percent of departments used pseudoplanar images in addition to SPECT images. CONCLUSION: In the 3 countries surveyed, SPECT has largely replaced planar imaging for evaluation of PE, with almost half of the SPECT studies incorporating a CT acquisition. Criteria used for interpretation are inconsistent, especially for planar imaging. PMID- 26135111 TI - Beyond 18F-FDG: Characterization of PET/CT and PET/MR Scanners for a Comprehensive Set of Positron Emitters of Growing Application--18F, 11C, 89Zr, 124I, 68Ga, and 90Y. AB - This study aimed to investigate image quality for a comprehensive set of isotopes ((18)F, (11)C, (89)Zr, (124)I, (68)Ga, and (90)Y) on 2 clinical scanners: a PET/CT scanner and a PET/MR scanner. METHODS: Image quality and spatial resolution were tested according to NU 2-2007 of the National Electrical Manufacturers Association. An image-quality phantom was used to measure contrast recovery, residual bias in a cold area, and background variability. Reconstruction methods available on the 2 scanners were compared, including point spread-function correction for both scanners and time of flight for the PET/CT scanner. Spatial resolution was measured using point sources and filtered backprojection reconstruction. RESULTS: With the exception of (90)Y, small differences were seen in the hot-sphere contrast recovery of the different isotopes. Cold-sphere contrast recovery was similar across isotopes for all reconstructions, with an improvement seen with time of flight on the PET/CT scanner. The lower-statistic (90)Y scans yielded substantially lower contrast recovery than the other isotopes. When isotopes were compared, there was no difference in measured spatial resolution except for PET/MR axial spatial resolution, which was significantly higher for (124)I and (68)Ga. CONCLUSION: Overall, both scanners produced good images with (18)F, (11)C, (89)Zr, (124)I, (68)Ga, and (90)Y. PMID- 26135112 TI - Determination of Skeletal Tumor Burden on 18F-Fluoride PET/CT. AB - The purpose of this study was to define a method to assess skeletal tumor burden with 18F-labeled sodium fluoride PET/CT (18F-fluoride PET/CT) and evaluate the reproducibility of these measurements. METHODS: Ninety-eight consecutive patients (90 men; mean age+/-SD, 65.7+/-14.2 y) underwent 158 18F-fluoride PET/CT scans for evaluation of skeletal metastatic disease. In order to determine the mean normal bone SUV, initially a 1-cm spheric volume of interest (VOI) was placed over 5 bone sites: T12, L5, sacrum, right iliac bone, and right femur. For each patient, the mean SUVmax for all sites was generated. Afterward, a threshold value of normal bone uptake was established. Subsequently, skeletal tumor burden was determined by generating volumetric data using a whole-body segmentation method. Any SUVmax below the normal threshold was excluded from analysis, as were VOIs not related to metastatic disease. Statistics for the remaining VOIs were then generated and defined as the skeletal metastatic tumor burden by 2 parameters: total lesion fluoride uptake above an SUVmax of 10 (TLF10) and fluoride tumor volume above an SUVmax of 10 (FTV10). TLF10 and FTV10 reproducibility was determined using 2 independent and experienced PET/CT interpreters analyzing a subset of 13 18F-fluoride PET/CT scans. RESULTS: Mean (+/-SD) normal bone SUVmax was 6.62+/-1.55 for T12, 6.11+/-1.73 for L5, 4.59+/ 1.74 for sacrum, 5.39+/-1.72 for right iliac bone, and 3.90+/-1.57 for right femur. The mean normal SUVmax for all 543 sites was 5.32+/-0.99. On the basis of these values, an SUVmax threshold of 10 was chosen to exclude normal bone from the volumetric calculations. Semiautomated measurements of TLF10 and FTV10 exhibited high interobserver reproducibility, within +/-0.77% and +/-3.62% of the interinterpreter average for TLF10 and FTV10, respectively. CONCLUSION: Determination of skeletal tumor burden with 18F-fluoride PET/CT is feasible and highly reproducible. Using an SUVmax threshold of 10 excludes nearly all normal bone activity from volumetric calculations. PMID- 26135113 TI - TGF-beta Antibody Uptake in Recurrent High-Grade Glioma Imaged with 89Zr Fresolimumab PET. AB - Transforming growth factor-beta (TGF-beta) signaling is involved in glioma development. The monoclonal antibody fresolimumab (GC1008) can neutralize all mammalian isoforms of TGF-beta, and tumor uptake can be visualized and quantified with (89)Zr-fresolimumab PET in mice. The aim of this study was to investigate the fresolimumab uptake in recurrent high-grade gliomas using (89)Zr-fresolimumab PET and to assess treatment outcome in patients with recurrent high-grade glioma treated with fresolimumab. METHODS: Patients with recurrent glioma were eligible. After intravenous administration of 37 MBq (5 mg) of (89)Zr-fresolimumab, PET scans were acquired on day 2 or day 4 after tracer injection. Thereafter, patients were treated with 5 mg of fresolimumab per kilogram intravenously every 3 wk. (89)Zr-fresolimumab tumor uptake was quantified as maximum standardized uptake value (SUVmax). MR imaging for response evaluation was performed after 3 infusions or as clinically indicated. RESULTS: Twelve patients with recurrent high-grade glioma were included: 10 glioblastomas, 1 anaplastic oligodendroglioma, and 1 anaplastic astrocytoma. All patients underwent (89)Zr fresolimumab PET 4 d after injection. In 4 patients, an additional PET scan was obtained on day 2 after injection. SUVmax on day 4 in tumor lesions was 4.6 (range, 1.5-13.9) versus a median SUVmean of 0.3 (range, 0.2-0.5) in normal brain tissue. All patients showed clinical or radiologic progression after 1-3 infusions of fresolimumab. Median progression-free survival was 61 d (range, 25 80 d), and median overall survival was 106 d (range, 37-417 d). CONCLUSION: (89)Zr-fresolimumab penetrated recurrent high-grade gliomas very well but did not result in clinical benefit. PMID- 26135114 TI - Quantification of Dynamic 11C-Phenytoin PET Studies. AB - The overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresistance in epilepsy. Recently, (11)C-phenytoin has been evaluated preclinically as a tracer for Pgp. The aim of the present study was to assess the optimal plasma kinetic model for quantification of (11)C-phenytoin studies in humans. METHODS: Dynamic (11)C-phenytoin PET scans of 6 healthy volunteers with arterial sampling were acquired twice on the same day and analyzed using single- and 2-tissue-compartment models with and without a blood volume parameter. Global and regional test-retest (TRT) variability was determined for both plasma to tissue rate constant (K1) and volume of distribution (VT). RESULTS: According to the Akaike information criterion, the reversible single-tissue-compartment model with blood volume parameter was the preferred plasma input model. Mean TRT variability ranged from 1.5% to 16.9% for K1 and from 0.5% to 5.8% for VT. Larger volumes of interest showed better repeatabilities than smaller regions. A 45-min scan provided essentially the same K1 and VT values as a 60-min scan. CONCLUSION: A reversible single-tissue compartment model with blood volume seems to be a good candidate model for quantification of dynamic (11)C-phenytoin studies. Scan duration may be reduced to 45 min without notable loss of accuracy and precision of both K1 and VT, although this still needs to be confirmed under pathologic conditions. PMID- 26135115 TI - Directional radiation of Babinet-inverted optical nanoantenna integrated with plasmonic waveguide. AB - We present a Babinet-inverted optical nanoantenna integrated with a plasmonic waveguide. Using an integrated nanoantenna, we can couple the plasmon guide mode in a metal-insulator-metal (MIM) structure into the resonant antenna feed directly. The resonantly excited feed slot then radiates to free space and generates a magnetic dipole-like far-field pattern. The coupling efficiency of the integrated nanoantenna is calculated as being approximately 19% using a three dimensional finite-difference time-domain (3D FDTD) simulation. By adding an auxiliary groove structure along with the feed, the radiation direction can be controlled similar to an optical Yagi-Uda antenna. We also determine, both theoretically and experimentally, that groove depth plays a significant role to function groove structure as a reflector or a director. The demonstrated Babinet inverted optical nanoantenna integrated with a plasmonic waveguide can be used as a "plasmonic via" in plasmonic nanocircuits. PMID- 26135116 TI - Deficiencies in public understanding about tobacco harm reduction: results from a United States national survey. AB - BACKGROUND: Tobacco products differ in their relative health harms. The need for educating consumers about such harms is growing as different tobacco products enter the marketplace and as the FDA moves to regulate and educate the public about different products. However, little is known about the patterns of the public's knowledge of relative harms. METHODS: Data were analyzed from the Health Information National Trends Survey (HINTS) 4 Cycle 2, a population-representative survey of US adults conducted between October 2012 and January 2013 (N = 3630). Participants reported their perceptions of the relative risks of e-cigarettes, smokeless tobacco, and different types of cigarettes compared to "traditional" cigarettes. Relative risk perceptions for each product type, as well as the consistency and accuracy of harm reduction beliefs, were analyzed. RESULTS: About 65% of the respondents accurately reported that no cigarettes were less harmful than any others. Slightly more than half of U.S. adults perceived e-cigarettes to be safer than regular cigarettes, a belief in line with current scientific evidence. By contrast, only 9% of respondents perceived some smokeless tobacco products to be safer, a belief strongly supported by the evidence. Only 3.5% of respondents had patterns of relative risk perceptions in line with current scientific evidence for all three modalities. CONCLUSIONS: The discrepancy between current evidence and public perceptions of relative risk of various tobacco/nicotine products was marked; for most tobacco types, a large proportion of the population held inaccurate harm reduction beliefs. Although there was substantial awareness that no cigarettes were safer than any other cigarettes, there could be benefits from increasing the percentage of the public that appreciates this fact, especially among current smokers. Given the potential benefits of tobacco risk reduction strategies, public health education efforts to increase understanding of basic harm reduction principles are needed to address these misperceptions. PMID- 26135117 TI - [Lymphangioma of the tongue]. PMID- 26135118 TI - [Rare finding of the inner ear after trauma]. PMID- 26135119 TI - [Discrimination of Hearing Disorder by Means of CLS and OAE in Vestibular Schwannoma]. AB - INTRODUCTION: Currently a sensitive early diagnosis of small vestibular schwannoma is only possible by using magnetic resonance imaging (MRI). OBJECTIVES: The main objective was a differentiation of the cochlear and retrocochlear component of small vestibular schwannoma with the help of categorial loudness scaling (CLS) and the growth function of otoacoustic emissions (DPOAE I/O-functions). MATERIAL AND METHODS: 34 patients (gr. 1: 17 patients with vestibular schwannoma <=15 mm, gr. 2: 17 matched patients with an inner ear hearing disorder) were examined. Besides audiological standard procedures they also underwent CLS according to the Wurzburger auditory field and a generation of DPOAE I/O-functions was conducted on the probands. RESULTS: The gradients of the loudness growth function as part of the CLS and the DPOAE I/O functions showed with few exceptions [500 Hz at 0-10 dB HL during CLS (p=0,040)] no significant differences between the groups (all p>0.05). A recruitment verification with the help of CLS was possible for tumors starting at a size of 5.45,mm at 3,000 and 4,000 Hz, respectively for tumors exceeding the size of 6.85 mm at 6,000 Hz with 100% sensitivity but only low specificity. CONCLUSIONS: A differentiation between a vestibular schwannoma and a mere cochlear hearing disorder with only the help of CLS and DPOAE I/O-functions is not possible. The results corroborate the thesis of an additional cochlear component even in small vestibular schwannoma. The implementation of CLS to determine cochlear deficits linked to vestibular schwannoma seems to be medically sensible if the tumor size exceeds 5 mm. According to the diagnostic method used to determine vestibular schwannoma MRI remains the first choice procedure. PMID- 26135120 TI - Why bother using non-human primate models of cognitive disorders in translational research? AB - Although everyone would agree that successful translation of therapeutic candidates for central nervous disorders should involve non-human primate (nhp) models of cognitive disorders, we are left with the paucity of publications reporting either the target validation or the actual preclinical testing in heuristic nhp models. In this review, we discuss the importance of nhps in translational research, highlighting the advances in technological/methodological approaches for 'bridging the gap' between preclinical and clinical experiments. In this process, we acknowledge that nhps remain a vital tool for the investigation of complex cognitive functions, given their resemblance to humans in aspects of behaviour, anatomy and physiology. The recent improvements made for a suitable nhp model in cognitive research, including new surrogates of disease and application of innovative methodological approaches, are continuous strides for reaching efficient translation for human benefit. This will ultimately aid the development of innovative treatments against the current and future threat of neurological and psychiatric disorders to the global population. PMID- 26135121 TI - Comparison of three surgical approaches for cervicothoracic spinal tuberculosis: a retrospective case-control study. AB - STUDY DESIGN: This is a retrospective case-control study. OBJECTIVES: The surgical approaches to cervicothoracic spinal tuberculosis (CTSTB) were controversial. The aim of this research is to retrospectively compare the efficacy and feasibility of anterior-only (AO) approach, combined anterior and posterior (AP) surgeries, and posterior-only (PO) approach for the treatment of CTSTB. METHODS: AO approach was undertaken in 20 patients (group A), AP fusion was carried out in 18 patients (group B), and PO surgery was performed in 21 patients (group C). Surgery duration, intraoperative blood loss, length of hospitalization, neurological status, kyphosis angle correction, loss of correction, and complications of the three groups were compared. RESULTS: Three surgical approaches all improved the kyphosis deformity and neurological function significantly (P < 0.05). The mean loss of correction in group A in the final follow-up was higher than in groups B and C (P < 0.05), and the difference between groups B and C was not significant (P > 0.05). The mean operation time, blood loss, and hospitalization days in group B were greater than in groups A and C. Complications were most prevalent in group A, more in group B, and the least in group C. CONCLUSION: The AO approach surgery should be limitedly used for severe CTSTB. The AP approach had got satisfactory clinical and radiographic outcomes, but with larger trauma and more complications, which should be reservedly performed for mild CTSTB. Compared to traditional surgery, PO surgery can significantly improve clinical results and obviously relieve postoperative complications. PMID- 26135123 TI - Correction: Identifying Human Genome-Wide CNV, LOH and UPD by Targeted Sequencing of Selected Regions. PMID- 26135122 TI - Exploring researchers' experiences of working with a researcher-driven, population-specific community advisory board in a South African schizophrenia genomics study. AB - BACKGROUND: Community engagement within biomedical research is broadly defined as a collaborative relationship between a research team and a group of individuals targeted for research. A Community Advisory Board (CAB) is one mechanism of engaging the community. Within genomics research CABs may be particularly relevant due to the potential implications of research findings drawn from individual participants on the larger communities they represent. Within such research, CABs seek to meet instrumental goals such as protecting research participants and their community from research-related risks, as well as intrinsic goals such as promoting the respect of participants and their community. However, successful community engagement depends on the degree to which CABs legitimately represent and engage with communities targeted for research. Currently, there is little literature describing the use of CABs in genomics research taking place in developing countries, and even less in the field of genomics research relating to mental illness. The aim of this article is to describe and consider the contributions made by a researcher-driven, population-specific CAB in a genomics of schizophrenia research project taking place in South Africa, from the perspective of the research team. DISCUSSION: Four broad discussion topics emerged during the CAB meetings namely: 1) informed consent procedures, 2) recruitment strategies, 3) patient illness beliefs and stigma experiences, and 4) specific ethical concerns relating to the project. The authors consider these discussions in terms of their contributions to instrumental and intrinsic goals of community engagement. The CAB gave valuable input on the consent processes and materials, recruitment strategies and suggested ways of minimizing the potential for stigma and discrimination. All of these contributions were of an instrumental nature, and helped improve the way in which the research took place. In addition, and perhaps more importantly, the CAB made a unique and important contribution relating to intrinsic functions such as promoting the respect and dignity of research participants and their community. This was particularly evident in ensuring sensitivity and respect of the community's traditional beliefs about schizophrenia and its treatment, and in this way promoting a respectful relationship between the research team and the participants. PMID- 26135124 TI - Guanchochroma wildpretii gen. et spec. nov. (Ochrophyta) Provides New Insights into the Diversification and Evolution of the Algal Class Synchromophyceae. AB - A new relative of the chrysophyte genus Chrysopodocystis was found in Tenerife and termed Guanchochroma wildpretii. This unicellular alga was most noticeably discernible from Chrysopodocystis socialis (the only species of this genus) by the presence of a cyst-like stage with a multilayered lorica, which also functions as a dispersal unit and shows secondary wall growth. Secondary expansion of loricae (cell casings not involved in cell division, usually with a more or less pronounced opening) has never been observed previously and marks a unique feature of the new taxon. Plastids are non-randomly distributed within cells of G. wildpretii. 18S rRNA gene analyses identified the two species as sister lineages and placed them in a monophyletic group with the Synchromophyceae, a heterokont algal (Ochrophyta) class characterized by the presence of chloroplast complexes. Yet, neither Chrysopodocystis nor Guanchochroma showed this feature in ultrastructure analyses. Additionally, their 18S rRNA genes possessed distinct inserts, the highest GC-content known for Ochrophyta and exceptionally long branches on the Ochrophyta 18S rDNA phylogenetic tree, suggesting substantially increased substitution rates along their branch compared to Synchromophyceae. Plastid marker data (rbcL) recovered a monophyletic clade of Chrysopodocystis, Guanchochroma and Synchromophyceae as well, yet with lower supports for internal split order due to limited resolution of the marker. Evidence for the sequence of events leading to the formation of the plastid complex of Synchromophyceae still remains ambiguous because of the apparently short timeframe in which they occurred. PMID- 26135126 TI - A Common Mutation and a Novel Mutation in the HPGD Gene in Nine Patients with Primary Hypertrophic Osteoarthropathy. AB - Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease characterized by digital clubbing, periostosis, and pachydermia. The HPGD gene encoding 15-prostaglandin dehydrogenase and SLCO2A1 encoding one type of prostaglandin transporter were found to be responsible for PHO. Mutations of either gene would lead to increased level of prostaglandin E2 (PGE2), which might contribute to the constellation of the symptoms. The aim of the study was to analyze the HPGD gene and the clinical characteristics in nine patients with the diagnosis of PHO. Nine patients, (eight males and one female) including two siblings and seven sporadic cases, were enrolled in the study. Clinical features were summarized, and blood and urine samples were collected. Sanger method was used to sequence the HPGD gene to detect mutations. Urinary PGE2 and prostaglandin metabolite (PGE-M) levels for each patient were measured and compared to the healthy controls. A recurrent c.310_311delCT mutation was identified in all patients, of which six were homozygous, two were heterozygous, and one was compound heterozygous with this mutation and a novel heterozygous missense mutation c.488G>A (p.R163H). The levels of PGE2 in urine were much higher than normal in all patients, along with lower PGE-M levels. In conclusion, nine PHO patients were characterized by typical clinical manifestations including digital clubbing, periostosis, and pachydermia. A common mutation and a novel mutation in HPGD gene were identified to be responsible for the disease, and c.310_311delCT mutation is likely to be a hot-spot mutation site for Asian PHO patients. PMID- 26135125 TI - What parents know and want to learn about healthy eating and body image in preschool children: a triangulated qualitative study with parents and Early Childhood Professionals. AB - BACKGROUND: Interventions for parents to encourage healthy eating in children often do not address parental feeding practices and body image development. METHODS: The current study investigated what parents (of children aged 1-6 years) understand about child healthy eating and body image, and what they would like in future interventions, by using structured focus groups with parents, and individual interviews with Early Childhood Professionals. Forty three parents (M(age) = 36.95 years, 93% female, 79% university degree) participated across 9 focus groups. Eleven Early Childhood Professionals (M(age) = 51.04, 100% female, 64% university degree, 64% Maternal and Child Health Nurses, 36% Childcare Centre Directors) completed individual telephone interviews. RESULTS: Parents described healthy eating as a variety, balance, and range of foods as well as limiting certain foods, such as the intake of sugar, salt, and processed foods. Most often parents defined child body image as a child's physical appearance and did not mention thoughts and feelings related to appearance or body experiences. Body image was most commonly considered a problem in early adolescence and often not an issue of relevance in early childhood. Parents appeared knowledgeable about nutrition and accessed information about healthy eating across a range of resources though rarely accessed information about child body image. They desired more practical information about how to avoid encouraging negative body image when promoting healthy eating. Professionals' responses confirmed these findings. CONCLUSIONS: Results suggest future interventions need to stress the important role positive body image plays in encouraging healthy attitudes to food and weight management, and the benefits positive body image can have on the health and mental health of preschool children. PMID- 26135127 TI - The value of multifocal electroretinography to predict progressive visual acuity loss in early AMD. AB - BACKGROUND: To investigate, in a prospective study, the role of multifocal electroretinography (mfERG) for predicting visual acuity decline in early age related macular degeneration (AMD) with time. METHODS: Twenty-six early AMD patients (12 males and 14 females, mean age 66.9 +/- 9.8; range 46-82 years) were included in the study. A complete ophthalmic examination and mfERG (Retiscan, Roland Germany, ISCEV standard protocol) were performed at the study entry (baseline), after 20 and 24 months. The first-order kernel mfERG responses were analyzed by ring analysis. The amplitude density (AD) of the first positive peak (P1, nV/deg(2)), the P1 amplitude (uV) and P1 implicit time (ms) for Rings 1 (central) to 6 (most peripheral) were evaluated. Data were statistically analyzed by analysis of variance and receiver operating characteristic (ROC) curves. RESULTS: The loss in the mfERG Ring 1 AD from normal control values, recorded at baseline, was correlated with the decrease in ETDRS visual acuity with time (P = 0.004). ROC analysis showed that, after 24 months, the average decline in visual acuity was greater (3 letters vs 0.4 letters, P = 0.0021) in patients whose Ring 1 P1 AD at baseline was equal to or less than 65.9 nV/deg(2), compared to those with higher AD values. Both P1 amplitude and AD of Ring 1 had an area under the curve of 0.702 (95% confidence interval 0.50-0.92) with a sensitivity of 64.3% (35.14-87.24%) and a specificity of 91.7% (61.52-99.79%). CONCLUSIONS: The present results indicate that mfERG P1 amplitude and AD of Ring 1 may be highly specific to predict visual acuity decline in early AMD. PMID- 26135132 TI - Risk of neurodevelopmental abnormalities in children treated with propranolol. PMID- 26135128 TI - Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of beta-Catenin. AB - BACKGROUND: The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. METHODS: BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and beta-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. RESULTS: COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, beta-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05). CONCLUSION: Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of beta-catenin. PMID- 26135129 TI - An Ikaros Promoter Element with Dual Epigenetic and Transcriptional Activities. AB - Ikaros DNA binding factor plays critical roles in lymphocyte development. Changes in Ikaros expression levels during lymphopoiesis are controlled by redundant but also unique regulatory elements of its locus that are critical for this developmental process. We have recently shown that Ikaros binds its own locus in thymocytes in vivo. Here, we evaluated the role of an Ikaros binding site within its major lympho-myeloid promoter. We identified an Ikaros/Ets binding site within a promoter sub-region that was highly conserved in mouse and human. Deletion of this binding site increased the percentage of the reporter-expressing mouse lines, indicating that its loss provided a more permissive chromatin environment. However, once transcription was established, the lack of this site decreased transcriptional activity. These findings implicate a dual role for Ikaros/Ets1 binding on Ikzf1 expression that is exerted at least through its promoter. PMID- 26135133 TI - Two-Dimensional Analysis of Air-Water Interface on Superhydrophobic Grooves under Fluctuating Water Pressure. AB - We theoretically investigate the collapse (i.e., wetting) transition of the air water interface on fully submerged superhydrophobic surfaces with micro-sized grooves under the fluctuating water pressure and the diffusion of the trapped air pockets. For the analysis, a nonlinear oscillator equation to describe the dynamics of the two-dimensional air-water interface on a single groove is derived, which is solved for a range of parameters of groove geometry and harmonically fluctuating water pressure. The results show that the pressure fluctuation across the interface encourages the early collapse of a plastron before reaching the critical hydrostatic pressure (i.e., maximum immersion depth) predetermined by the geometry. The dependence of plastron longevity on the surface geometry is found such that the plastron on a narrow groove (<=~5 MUm) (collapses mostly due to gas diffusion) lasts days while the ones on wider grooves (>~35-45 MUm, for example), more susceptible to the oscillating pressure, last a much shorter duration. The interplay between the air compression due to water impalement and the change of the volume of impaled water due to gas diffusion determines the response of plastron to fluctuating water pressure, which is analyzed in detail through the introduction of nondimensional parameters, and the critical groove width (most vulnerable to the external perturbations) is explained further. Finally, as a countermeasure to the fluctuating water pressure, it is suggested that the enhanced advancing contact angle of the groove sidewall (e.g., hierarchical structure) mitigates the negative effects. PMID- 26135134 TI - Insights into the Functional Roles of N-Terminal and C-Terminal Domains of Helicobacter pylori DprA. AB - DNA processing protein A (DprA) plays a crucial role in the process of natural transformation. This is accomplished through binding and subsequent protection of incoming foreign DNA during the process of internalization. DprA along with Single stranded DNA binding protein A (SsbA) acts as an accessory factor for RecA mediated DNA strand exchange. H. pylori DprA (HpDprA) is divided into an N terminal domain and a C- terminal domain. In the present study, individual domains of HpDprA have been characterized for their ability to bind single stranded (ssDNA) and double stranded DNA (dsDNA). Oligomeric studies revealed that HpDprA possesses two sites for dimerization which enables HpDprA to form large and tightly packed complexes with ss and dsDNA. While the N-terminal domain was found to be sufficient for binding with ss or ds DNA, C-terminal domain has an important role in the assembly of poly-nucleoprotein complex. Using site directed mutagenesis approach, we show that a pocket comprising positively charged amino acids in the N-terminal domain has an important role in the binding of ss and dsDNA. Together, a functional cross talk between the two domains of HpDprA facilitating the binding and formation of higher order complex with DNA is discussed. PMID- 26135135 TI - Origin and evolution of Petrocosmea (Gesneriaceae) inferred from both DNA sequence and novel findings in morphology with a test of morphology-based hypotheses. AB - BACKGROUND: Petrocosmea Oliver (Gesneriaceae) currently comprises 38 species with four non-nominate varieties, nearly all of which have been described solely from herbarium specimens. However, the dried specimens have obscured the full range of extremely diverse morphological variation that exists in the genus and has resulted in a poor subgeneric classification system that does not reflect the evolutionary history of this group. It is important to develop innovative methods to find new morphological traits and reexamine and reevaluate the traditionally used morphological data based on new hypothesis. In addition, Petrocosmea is a mid-sized genus but exhibits extreme diverse floral variants. This makes the genus of particular interest in addressing the question whether there are any key factors that is specifically associated with their evolution and diversification. RESULTS: Here we present the first phylogenetic analyses of the genus based on dense taxonomic sampling and multiple genes combined with a comprehensive morphological investigation. Maximum-parsimony, maximum likelihood and Bayesian analyses of molecular data from two nuclear DNA and six cpDNA regions support the monophyly of Petrocosmea and recover five major clades within the genus, which is strongly corroborated by the reconstruction of ancestral states for twelve new morphological characters directly observed from living material. Ancestral area reconstruction shows that its most common ancestor was likely located east and southeast of the Himalaya-Tibetan plateau. The origin of Petrocosmea from a potentially Raphiocarpus-like ancestor might have involved a series of morphological modifications from caulescent to acaulescent habit as well as from a tetrandrous flower with a long corolla-tube to a diandrous flower with a short corolla-tube, also evident in the vestigial caulescent habit and transitional floral form in clade A that is sister to the remainder of the genus. Among the five clades in Petrocosmea, the patterns of floral morphological differentiation are consistent with discontinuous lineage-associated morphotypes as a repeated adaptive response to alternative environments. CONCLUSION: Our results suggest that the lineage-specific morphological differentiations reflected in the upper lip, a functional organ for insect pollination, are likely adaptive responses to pollinator shifts. We further recognize that the floral morphological diversification in Petrocosmea involves several evolutionary phenomena, i.e. evolutionary successive specialization, reversals, parallel evolution, and convergent evolution, which are probably associated with adaptation to pollination against the background of heterogeneous abiotic and biotic environments in the eastern wing regions of Himalaya-Tibetan plateau. PMID- 26135136 TI - Informatics resources for the Collaborative Cross and related mouse populations. PMID- 26135137 TI - Clinical efficacy and pharmacokinetics of tacrolimus in children with steroid resistant nephrotic syndrome. AB - BACKGROUND: Tacrolimus has gained acceptance in the management of steroid resistant nephrotic syndrome (SRNS) in children. Due to limited data, therapeutic range is extrapolated from pediatric renal transplant recipients. This study was designed to assess therapeutic efficacy of tacrolimus in children with SRNS and its correlation with inter-dose area under concentration curve (AUC0-12 h) and trough concentration (C0). METHODS: Pre dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3, 4, 8, and 12 h after drug administration blood samples were collected in 25 children who were on tacrolimus for a minimum of 3 months and AUC0-12 h was calculated. RESULTS: There was an 80% (20/25) response rate with 64% (16/25) children achieving complete remission. Median C0 in remission was higher than in relapse group (2.95 ng/ml, versus 1.20 ng/ml, p = 0.005). Median AUC0-12 h in remission was higher compared to those in relapse group (79.75 versus 35.15 MUg * h/l; p = 0.025). Maximum concentration after drug administration (Cmax) among the groups was not significantly different. There was a significant correlation between C0 and AUC0-12 h (r = 0.79); and Cmax and AUC0-12 h (r = 0.84). Five patients had a rise in serum creatinine, of which four were still proteinuric and had lower C0 and AUC0-12 h. No other adverse effect was noted. CONCLUSIONS: Tacrolimus had beneficial clinical response in SRNS. Target C0 and AUC0-12 h level for treatment remission was higher than those in relapse in children with SRNS but was lower than required in transplant recipient. PMID- 26135138 TI - Proteinuria caused by glomerular hypertension during adolescence associated with extremely premature birth: a report of two cases. AB - BACKGROUND: Prematurity and low birth weight are risk factors for the future development of chronic kidney disease (CKD) and hypertension caused by fewer nephrons with limited filtration surface area. Few reports to date have evaluated their clinical backgrounds and pathological findings, including glomerular hypertension and focal segmental glomerulosclerosis. CASE-DIAGNOSIS/TREATMENT: This report describes two patients, a 15-year-old girl (patient 1), with a birth weight of 618 g and a gestational age of 24 weeks, and a 14-year-old boy (patient 2), with a birth weight of 842 g and a gestational age at 25 weeks. Both had a birth weight appropriate for gestational age. Both were first diagnosed with proteinuria during adolescence, and patient 2 also had hypertension. Pathological findings included glomerulomegaly in both and hypertrophy of the juxtaglomerular apparatus and perihilar glomerulosclerosis in patient 1, suggesting glomerular hypertension. Treatment with lisinopril resulted in the immediate disappearance of proteinuria. Renal dysfunction was observed in both patients, but neither showed evidence of severe aggravation after a follow-up of 5 or 6 years. CONCLUSIONS: Proteinuria in both patients was caused by glomerular hypertension with hyperfiltration. Extremely preterm birth itself may be a risk factor for future CKD. Long-term follow-up of patients born prematurely and at low birth weight, including urinalysis and blood pressure measurements, is necessary to diagnose and treat late renal complications. PMID- 26135139 TI - Elevated uric acid and obesity-related cardiovascular disease risk factors among hypertensive youth. AB - BACKGROUND: Uric acid (UA) is associated with high blood pressure in adolescents and with left ventricular hypertrophy (LVH) and cardiovascular disease (CVD) in adults. We sought to determine if UA is independently associated with CVD risk factors and left ventricular mass (LVM) over time in hypertensive youth. METHODS: This was a 1-year prospective observational study of hypertensive children aged 3 19 years. Cross-sectional and longitudinal associations of serum UA with CVD risk factors and LVM were explored. RESULTS: Of the 49 children who completed both the baseline and 12-month assessments, at baseline the mean age was 13.8 years and mean UA was 5.5 mg/dL; 24% had elevated UA, 51% were overweight/obese and 39% had LVH. Measures of adiposity, low high-density lipoprotein cholesterol, high sensitivity C-reactive protein, LVM and LVH were all significantly associated with elevated UA at baseline, but not with change over time. Each 1 mg/dL increase in baseline UA was associated with a 2.5 g/m(2.7) increase in the LVM index at follow-up (95% confidence interval 0.64, 4.39; p = 0.01); after adjustment for age, sex, race, body mass index z-score, change in UA, time, blood pressure and medication use, this association was no longer significant. CONCLUSIONS: Hypertensive children with elevated UA have a higher prevalence of obesity-related CVD risk factors. Among hypertensive children, UA may be a marker of adiposity and not an independent CVD risk factor. PMID- 26135141 TI - HOXA1 enhances the cell proliferation, invasion and metastasis of prostate cancer cells. AB - HOXA1, a member of the HOX gene family, has been implicated in tumor progression. However, the role of HOXA1 in prostate cancer is not well-established. In the present study, we found that HOXA1 was highly expressed in prostate cancer cells. We then repressed the expression of HOXA1 by short hairpin RNA (shRNA) to investigate the function of HOXA1 in prostate cancer cells. Our in vitro data showed that knockdown of HOXA1 attenuated the growth, invasion and migration of prostate cancer DU-145 and PC-3 cells. Furthermore, knockdown of HOXA1 resulted in an increased E-cadherin level and decreased Snail and MMP-3 levels in the DU 145 cells. In addition, knockdown of HOXA1 inhibited activation of ERK1/2 and AKT in the DU-145 cells. Our in vivo data revealed that knockdown of HOXA1 suppressed the growth and metastasis of prostate cancer cells. Collectively, our findings suggest that HOXA1 is involved in the regulation of prostate cancer progression, including cell growth, migration, invasion and metastasis. Thus, downregulation of HOXA1 may be a novel approach for the treatment of prostate cancer. PMID- 26135140 TI - Protease inhibitors to treat hepatitis C in the Swiss HIV Cohort Study: high efficacy but low treatment uptake. AB - OBJECTIVES: Direct-acting antiviral agents (DAAs) have become the standard of care for the treatment of chronic hepatitis C virus (HCV) infection. We aimed to assess treatment uptake and efficacy in routine clinical settings among HIV/HCV coinfected patients after the introduction of the first generation DAAs. METHODS: Data on all Swiss HIV Cohort Study (SHCS) participants starting HCV protease inhibitor (PI) treatment between September 2011 and August 2013 were collected prospectively. The uptake and efficacy of HCV therapy were compared with those in the time period before the availability of PIs. RESULTS: Upon approval of PI treatment in Switzerland in September 2011, 516 SHCS participants had chronic HCV genotype 1 infection. Of these, 57 (11%) started HCV treatment during the following 2 years with either telaprevir, faldaprevir or boceprevir. Twenty-seven (47%) patients were treatment-naive, nine (16%) were patients with relapse and 21 (37%) were partial or null responders. Twenty-nine (57%) had advanced fibrosis and 15 (29%) had cirrhosis. End-of-treatment virological response was 84% in treatment-naive patients, 88% in patients with relapse and 62% in previous nonresponders. Sustained virological response was 78%, 86% and 40% in treatment naive patients, patients with relapse and nonresponders, respectively. Treatment uptake was similar before (3.8 per 100 patient-years) and after (6.1 per 100 patient-years) the introduction of PIs, while treatment efficacy increased considerably after the introduction of PIs. CONCLUSIONS: The introduction of PI based HCV treatment in HIV/HCV-coinfected patients improved virological response rates, while treatment uptake remained low. Therefore, the introduction of PIs into the clinical routine was beneficial at the individual level, but had only a modest effect on the burden of HCV infection at the population level. PMID- 26135142 TI - A Semisynthetic Strategy Leads to Alteration of the Backbone Amidate Ligand in the NiSOD Active Site. AB - Computational investigations have implicated the amidate ligand in nickel superoxide dismutase (NiSOD) in stabilizing Ni-centered redox catalysis and in preventing cysteine thiolate ligand oxidation. To test these predictions, we have used an experimental approach utilizing a semisynthetic scheme that employs native chemical ligation of a pentapeptide (HCDLP) to recombinant S. coelicolor NiSOD lacking these N-terminal residues, NDelta5-NiSOD. Wild-type enzyme produced in this manner exhibits the characteristic spectral properties of recombinant WT NiSOD and is as catalytically active. The semisynthetic scheme was also employed to construct a variant where the amidate ligand was converted to a secondary amine, H1*-NiSOD, a novel strategy that retains a backbone N-donor atom. The H1* NiSOD variant was found to have only ~1% of the catalytic activity of the recombinant wild-type enzyme, and had altered spectroscopic properties. X-ray absorption spectroscopy reveals a four-coordinate planar site with N2S2-donor ligands, consistent with electronic absorption spectroscopic results indicating that the Ni center in H1*-NiSOD is mostly reduced in the as-isolated sample, as opposed to 50:50 Ni(II)/Ni(III) mixture that is typical for the recombinant wild type enzyme. The EPR spectrum of as-isolated H1*-NiSOD accounts for ~11% of the Ni in the sample and is similar to WT-NiSOD, but more axial, with gz < gx,y. (14)N-hyperfine is observed on gz, confirming the addition of the apical histidine ligand in the Ni(III) complex. The altered electronic properties and implications for redox catalysis are discussed in light of predictions based on synthetic and computational models. PMID- 26135144 TI - Ethical issues in publishing. PMID- 26135143 TI - The Impact of a Community Awareness Strategy on Caregiver Treatment Seeking Behaviour and Use of Artemether-Lumefantrine for Febrile Children in Rural Kenya. AB - BACKGROUND: Access to prompt and effective treatment is the cornerstone for malaria control. Population Services International in collaboration with the Ministry of Health launched a malaria behaviour change communication intervention in Nyanza province, Kenya. The initiative aimed to improve: symptom recognition and prompt access to government health facilities for febrile children; effective treatment with the recommended first-line drug artemether-lumefantrine (AL) in public health facilities and adherence to the AL regimen. METHODS: Pre- and post intervention cross-sectional household surveys were used to evaluate the impact of the intervention on prompt and correct use of AL for febrile children below five years of age. The primary outcome was the proportion of children below five years of age with fever in the last 14 days accessing AL within 48 hours of fever onset. RESULTS: There was an increase from 62.8% pre-intervention to 79.4% post intervention (95% CI: 11.1, 22.1) in caregivers who reported seeking formal treatment promptly (on the same day, or next day) for their febrile children. However, there was a decrease in the use of government health facilities in the post-intervention period. There was a small increase in the proportion of children accessing AL within 48 hours of fever onset [18.4% vs 23.5% (0.1-10.0)]. CONCLUSION: The findings of this evaluation demonstrate that interventions that target only one sector may have a limited impact on improvements in prompt and effective treatment where multiple sources of treatments are sought for febrile illness. Additionally, the context in which an intervention is implemented is likely to influence the process and outcomes. PMID- 26135146 TI - Stories from unaccompanied children in immigration detention: A composite account. PMID- 26135145 TI - Summary of position statement on refugee and asylum-seeker health. PMID- 26135147 TI - Sadness and fear: The experiences of children and families in remote Australian immigration detention. PMID- 26135149 TI - Where did the oral tube originate from? PMID- 26135148 TI - Pain from bluebottle jellyfish stings. AB - An 11-year-old girl presented to the emergency department with severe pain after a jellyfish sting at a New South Wales beach. Bluebottle (Physalia) jellyfish was deemed the most likely cause considering her geographical location. The Australian Resuscitation Council Guideline (2010) suggests immersing in water as hot as can be tolerated for 20 min for treating pain from jellyfish stings. This guideline was written based on past case reports, books and randomised controlled trials (RCTs). We performed a search to assess the most current evidence for relief of pain from Bluebottle jellyfish stings, which yielded two systematic reviews and seven RCTs. Both systematic reviews had similar conclusions, with one of the RCTs used in both reviews showing the most relevance to our presenting patient in terms of demographics, location and jellyfish type. This journal club article is an appraisal of this RCT by Loten et al. and the validity of its conclusion that hot water immersion is most effective for the relief of pain from Bluebottle stings. PMID- 26135150 TI - Congenital anomaly. PMID- 26135156 TI - A unique method of oral ulceration management in a patient with pathological tongue thrust. PMID- 26135157 TI - Potential Ebola prophylaxis. PMID- 26135158 TI - Profound hypomagnesaemia secondary to alternative therapy in a child with autism spectrum disorder. PMID- 26135159 TI - Hitchhiker's guide to the literature: Journal: Gut. PMID- 26135161 TI - Primary Cytomegalovirus Syndrome: An Unexpected Cause of Donor Morbidity Shortly After Right Lobectomy for Living-Donor Liver Transplant. AB - We present a case of initially unexplained fever in a living right liver lobe transplant donor that turned out to be due to primary cytomegalovirus infection. PMID- 26135160 TI - Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes. AB - The increasing burden of dengue, and the relative failure of traditional vector control programs highlight the need to develop new control methods. SIT using self-limiting genetic technology is one such promising method. A self-limiting strain of Aedes aegypti, OX513A, has already reached the stage of field evaluation. Sustained releases of OX513A Ae. aegypti males led to 80% suppression of a target wild Ae. aegypti population in the Cayman Islands in 2010. Here we describe sustained series of field releases of OX513A Ae. aegypti males in a suburb of Juazeiro, Bahia, Brazil. This study spanned over a year and reduced the local Ae. aegypti population by 95% (95% CI: 92.2%-97.5%) based on adult trap data and 81% (95% CI: 74.9-85.2%) based on ovitrap indices compared to the adjacent no-release control area. The mating competitiveness of the released males (0.031; 95% CI: 0.025-0.036) was similar to that estimated in the Cayman trials (0.059; 95% CI: 0.011-0.210), indicating that environmental and target strain differences had little impact on the mating success of the OX513A males. We conclude that sustained release of OX513A males may be an effective and widely useful method for suppression of the key dengue vector Ae. aegypti. The observed level of suppression would likely be sufficient to prevent dengue epidemics in the locality tested and other areas with similar or lower transmission. PMID- 26135162 TI - Cancer registries in Africa 2014: A survey of operational features and uses in cancer control planning. AB - A questionnaire survey of all active population based cancer registries in sub Saharan Africa obtained information on their characteristics (size, staffing, funding), methods of working, the nature of any links between registries and their respective Health Authorities (national and/or local), and the use of their data in research or cancer control planning. 23/25 registries (92%) responded. Sources of direct funding and estimated amounts from each source were established, and suggest that it is approximately US$8-9 per case registered. Almost half of the funding is used for routine data collection, processing and analysis. Staffing levels vary, partly as a function of the registry size (approximately one FTE per 300 cases registered). Most data collection is active, using multiple sources (median 10 per registry), and is largely paper-based (abstraction onto paper forms), although all use the computer system CanReg(c) for data entry, storage and analysis. Most reporting by the registries is remarkably timely, and in general, their results are widely used by health authorities and other stakeholders in planning and evaluating services, while research output is much more variable. These registries are the source of almost all the existing information on cancer incidence and mortality in sub-Saharan Africa, as published in IARC's "Globocan". PMID- 26135163 TI - Staffing is still a divisive issue. PMID- 26135166 TI - Scrapping unsocial hours pay would be 'red line', college warns. PMID- 26135165 TI - NICE decision to stop work on safe staffing is 'backward step'. PMID- 26135167 TI - Pilot trust prepares staff for revalidation. PMID- 26135168 TI - Labour peer says L5 billion a year could be saved. PMID- 26135169 TI - Workers who take too much time off will have their pay docked. PMID- 26135170 TI - Prudent care puts the focus on evidence-based services. PMID- 26135171 TI - Poor end of life care is clear theme in ombudsman's report. PMID- 26135172 TI - Legal action: protect yourself. PMID- 26135173 TI - Ring of confidence. PMID- 26135177 TI - Vantage point--Disciplinary data unclear. PMID- 26135182 TI - How I used social media to boost my career. PMID- 26135186 TI - Don't be scared of the process, use it to motivate your practice. PMID- 26135193 TI - Service improvement as an experiential tool for postgraduate students and service providers. AB - A project developed at Buckinghamshire New University is connecting postgraduate students in health and social care programmes, including nursing, social work and safeguarding, with service providers seeking to undertake service improvement evaluations. The Service Improvement Research and Evaluation Partnerships project was evaluated using participatory action research (PAR) and found that students gained a variety of skills through experiential learning and that service providers gained postgraduate-level evaluation from enthusiastic students with minimal staff input. This article describes the project and explains how it can assist service providers to complete robust evaluations, and help students to engage in 'live' evaluations in situ for experiential learning. It also details the PAR evaluation. PMID- 26135194 TI - Dragons' Den: promoting healthcare research and innovation. AB - The changing health and social care landscape, and, in particular, the financial challenges affecting the NHS, can present difficulties for staff looking for funding to support innovation and new ways of working. One method of competitive tendering that is becoming more accepted as a way of allocating funds, encouraging staff engagement and developing innovation for research is a format based the BBC television series, Dragons' Den. This article describes how Hounslow and Richmond Community Healthcare NHS Trust, London, has developed a 'Dragons' Den initiative' of annual competitive research funding allocation to ensure that some of the most dynamic practice in the trust is captured. PMID- 26135196 TI - Shop-floor nous. PMID- 26135195 TI - Lessons from school: what nurse leaders can learn from education. AB - The drive to improve quality in the education sector is similar to that in health care, and lessons from the schools system are relevant to nursing leadership. This article discusses these shared traits, and details how school improvement was achieved in London and how a model of learning-centred leadership helped to transform pupil attainment in schools that had been performing poorly. Parallels are drawn between the education inspection system undertaken by Ofsted and the hospital inspections undertaken by the Care Quality Commission, and between the practice discipline-based managerial roles of nurse directors and head teachers. The article suggests that a learning-centred approach to improving the quality of patient care is needed, with a focus on the education and continuing professional development of staff. PMID- 26135198 TI - Renal biopsy in the elderly: a single-center experience. AB - OBJECTIVE: Aging population has been increasing worldwide. So the number of elderly patients presenting with kidney disease has also been increasing. In this retrospective study, we assessed biopsy results of elderly patients and their clinical presentations. MATERIALS AND METHODS: Native renal biopsy results of 98 elderly patients (>=65 years) were analyzed. These 98 patients consisted of 56 males (57.1 %) and 42 females (42.9 %) with a mean age of 70.59 +/- 5.31 years (65-88 years). RESULTS: The clinical presentations of our elderly patients were nephritic syndrome (n = 45), acute kidney injury (n = 35), nephrotic syndrome (n = 33), chronic kidney disease (n = 32) and combined nephritic and nephrotic syndrome (n = 14). In patients with nephritic syndrome, the most common diagnosis was crescentic GN (17.8 % type 3 and 13.3 % types 1 and 2). Crescentic GN was also the most frequent among patients with acute kidney injury (37.1 %), while membranous nephropathy was the major histopathological diagnosis in chronic kidney disease patients. In nephrotic syndrome, the most common histopathological diagnosis was AA amyloidosis. None of the patients had a major life-threatening complication. CONCLUSION: Biopsies in the elderly are as safe as in the general population. Renal biopsy should be performed to provide an accurate diagnosis and initiate specific treatment in elderly patients. PMID- 26135199 TI - Mechanical Ventilation as a Therapeutic Tool to Reduce ARDS Incidence. AB - Trauma, hemorrhagic shock, or sepsis can incite systemic inflammatory response syndrome, which can result in early acute lung injury (EALI). As EALI advances, improperly set mechanical ventilation (MV) can amplify early injury into a secondary ventilator-induced lung injury that invariably develops into overt ARDS. Once established, ARDS is refractory to most therapeutic strategies, which have not been able to lower ARDS mortality below the current unacceptably high 40%. Low tidal volume ventilation is one of the few treatments shown to have a moderate positive impact on ARDS survival, presumably by reducing ventilator induced lung injury. Thus, there is a compelling case to be made that the focus of ARDS management should switch from treatment once this syndrome has become established to the application of preventative measures while patients are still in the EALI stage. Indeed, studies have shown that ARDS incidence is markedly reduced when conventional MV is applied preemptively using a combination of low tidal volume and positive end-expiratory pressure in both patients in the ICU and in surgical patients at high risk for developing ARDS. Furthermore, there is evidence from animal models and high-risk trauma patients that superior prevention of ARDS can be achieved using preemptive airway pressure release ventilation with a very brief duration of pressure release. Preventing rather than treating ARDS may be the way forward in dealing with this recalcitrant condition and would represent a paradigm shift in the way that MV is currently practiced. PMID- 26135200 TI - Letter to the Editor. PMID- 26135201 TI - Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood. AB - Early-life adverse experiences, including prenatal stress (PNS), are associated with a higher prevalence of neurodevelopmental, cardiovascular and metabolic disorders in affected offspring. Here, in a rat model of chronic PNS, we investigate the impact of late gestational stress on physiological outcomes in adulthood. Sprague-Dawley pregnant dams were subjected to repeated restraint stress from embryonic day 14 to day 20, and their male offspring were assessed at 4 months of age. PNS induced an exaggeration of the hypothalamic-pituitary adrenal (HPA) axis response to stress, as well as an elevation of blood pressure and impairment of cognitive function. Altered respiratory control was also observed, as demonstrated by increased variability in basal respiratory frequency and abnormal frequency responses to both hypoxic and hypercapnic challenges. PNS also affected gastrointestinal neurodevelopment and function, as measured by a decrease in the innervation density of distal colon and an increase in the colonic secretory response to catecholaminergic stimulation. Finally, PNS induced long lasting alterations in the intestinal microbiota composition. 16S rRNA gene 454 pyrosequencing revealed a strong trend towards decreased numbers of bacteria in the Lactobacillus genus, accompanied by elevated abundance of the Oscillibacter, Anaerotruncus and Peptococcus genera in PNS animals. Strikingly, relative abundance of distinct bacteria genera significantly correlated with certain respiratory parameters and the responsiveness of the HPA axis to stress. Together, these findings provide novel evidence that PNS induces long-term maladaptive alterations in the gastrointestinal and respiratory systems, accompanied by hyper-responsiveness to stress and alterations in the gut microbiota. PMID- 26135202 TI - Novel Somatic Mutation in LEMD3 Splice Site Results in Buschke-Ollendorff Syndrome with Polyostotic Melorheostosis and Osteopoikilosis. AB - Buschke-Ollendorff syndrome is a rare autosomal dominant disorder caused by loss of function in LEMD3, resulting in connective tissue nevi and varying bone dysplasia. Although typically benign, we describe a novel LEMD3 splice site mutation (IVS12 + 1delG) in a 13-year-old boy with Buschke-Ollendorff syndrome presenting with severe skeletal deformities, polyostotic melorheostosis, and osteopoikilosis. PMID- 26135204 TI - Enneanuclear [Ni6Ln3] Cages: [Ln(III)3] Triangles Capping [Ni(II)6] Trigonal Prisms Including a [Ni6Dy3] Single-Molecule Magnet. AB - The use of (2-(beta-naphthalideneamino)-2-hydroxymethyl-1-propanol) ligand, H3L, in Ni/Ln chemistry has led to the isolation of three new isostructural [Ni(II)6Ln(III)3] metallic cages. More specifically, the reaction of Ni(ClO4)2.6H2O, the corresponding lanthanide nitrate salt, and H3L in MeCN, under solvothermal conditions in the presence of NEt3, led to the isolation of three complexes with the formulas [Ni6Gd3(OH)6(HL)6(NO3)3].5.75MeCN.2Et2O.1.5H2O (1.5.75MeCN.2Et2O.1.5H2O), [Ni6Dy3(OH)6(HL)6(NO3)3].2MeCN.2.7Et2O.2.4H2O (2.2MeCN.2.7Et2O.2.4H2O), and [Ni6Er3(OH)6(HL)6(NO3)3].5.75MeCN.2Et2O.1.5H2O (3.5.75MeCN.2Et2O.1.5H2O). The structure of all three clusters describes a [Ln(III)3] triangle capping a [Ni(II)6] trigonal prism. Direct current magnetic susceptibility studies in the 5-300 K range for complexes 1-3 reveal the different nature of the magnetic interactions within the clusters: dominant antiferromagnetic exchange interactions for the Dy(III) and Er(III) analogues and dominant ferromagnetic interactions for the Gd(III) example. Alternating current magnetic susceptibility measurements under zero external dc field displayed fully formed temperature- and frequency-dependent out-of-phase peaks for the [Ni(II)6Dy(III)3] analogue, establishing its single molecule magnetism behavior with Ueff = 24 K. PMID- 26135203 TI - Optimizing optogenetic constructs for control over signaling and cell behaviours. AB - Optogenetic tools have recently been developed that enable dynamic control over the activities of select signaling proteins. They provide the unique ability to rapidly turn signaling events on or off with subcellular control in living cells and organisms. This capability is leading to new insights into how the spatial and temporal coordination of signaling events governs dynamic cell behaviours such as migration and neurite outgrowth. These tools can also be used to dissect a protein's signaling functions at different organelles. Here we review the properties of photoreceptors from diverse organisms that have been leveraged to control signaling in mammalian cells. We emphasize recent engineering approaches that have been used to create optogenetic constructs with optimized spectral, kinetic, and signaling properties for controlling cell behaviours. PMID- 26135205 TI - Spin torque oscillator neuroanalog of von Neumann's microwave computer. AB - Frequency and phase of neural activity play important roles in the behaving brain. The emerging understanding of these roles has been informed by the design of analog devices that have been important to neuroscience, among them the neuroanalog computer developed by O. Schmitt and A. Hodgkin in the 1930s. Later J. von Neumann, in a search for high performance computing using microwaves, invented a logic machine based on crystal diodes that can perform logic functions including binary arithmetic. Described here is an embodiment of his machine using nano-magnetics. Electrical currents through point contacts on a ferromagnetic thin film can create oscillations in the magnetization of the film. Under natural conditions these properties of a ferromagnetic thin film may be described by a nonlinear Schrodinger equation for the film's magnetization. Radiating solutions of this system are referred to as spin waves, and communication within the film may be by spin waves or by directed graphs of electrical connections. It is shown here how to formulate a STO logic machine, and by computer simulation how this machine can perform several computations simultaneously using multiplexing of inputs, that this system can evaluate iterated logic functions, and that spin waves may communicate frequency, phase and binary information. Neural tissue and the Schmitt-Hodgkin, von Neumann and STO devices share a common bifurcation structure, although these systems operate on vastly different space and time scales; namely, all may exhibit Andronov-Hopf bifurcations. This suggests that neural circuits may be capable of the computational functionality as described by von Neumann. PMID- 26135206 TI - Genome evolution by transformation, expansion and contraction (GETEC). AB - We propose here the GETEC (Genome Evolution by Transformation, Expansion and Contraction) model of gene evolution based on substitution, insertion and deletion of genetic motifs. The GETEC model unifies two classes of evolution models: models of substitution, insertion and deletion of nucleotides as function of time (Lebre and Michel, 2010) and sequence length (Lebre and Michel, 2012), and models of symmetric substitution of genetic motifs as function of time (Benard and Michel, 2011). Evolution of genetic motifs based on substitution, insertion and deletion is modeled by a differential equation whose analytical solutions give an expression of the genetic motif occurrence probabilities as a function of time or sequence length, as well as in direct time direction (past present) or inverse time direction (present-past). Evolution models with "substitution only", i.e. without insertion and deletion, and with "insertion and deletion only", i.e. without substitution, are particular cases of the GETEC model. We have also developed a research software for computing the analytical solutions of the GETEC model. It is freely accessible at http://icube-bioinfo.u strasbg.fr/webMathematica/GETEC/ or via the web site http://dpt-info.u strasbg.fr/~michel/. PMID- 26135207 TI - Improvements in knee biomechanics during walking are associated with increased physical activity after total knee arthroplasty. AB - Total knee arthroplasty (TKA) in people with knee osteoarthritis increases knee specific and general physical function, but it has not been established if there is a relationship between changes in these elements of functional ability. This study investigated changes and relationships between knee biomechanics during walking, physical activity, and use of time after TKA. Fifteen people awaiting TKA underwent 3D gait analysis before and six months after surgery. Physical activity and use of time were determined in free-living conditions from a high resolution 24-h activity recall. After surgery, participants displayed significant improvements in sagittal plane knee biomechanics and improved their physical activity profiles, standing for 105 more minutes (p=0.001) and performing 64 min more inside chores on average per day (p=0.008). Changes in sagittal plane knee range of motion (ROM) and peak knee flexion positively correlated with changes in total daily energy expenditure, time spent undertaking moderate to vigorous physical activity, inside chores and passive transport (r=0.52-0.66, p=0.005-0.047). Restoration of knee function occurs in parallel and is associated with improvements in physical activity and use of time after TKA. Increased functional knee ROM is required to support improvements in total and context specific physical activity. PMID- 26135208 TI - Myocardin-related transcription factor-A-overexpressing bone marrow stem cells protect cardiomyocytes and alleviate cardiac damage in a rat model of acute myocardial infarction. AB - Myocardin-related transcription factor-A (MRTF-A) can transduce biomechanical and humoral signals, which can positively modulate cardiac damage induced by acute myocardial infarction (AMI). In the clinic, bone marrow stem cell (BMSC) therapy is being increasingly utilized for AMI; however, the effects of BMSC transplantation remain to be optimized. Therefore, a novel strategy to enhance BMSC-directed myocardial repair is particularly important. The present study was performed to assess the efficacy of MRTF-A-overexpressing BMSCs in a rat model of AMI. Primary cardiomyocytes were prepared from neonatal Sprague-Dawley rats and BMSCs were isolated from male Sprague-Dawley rats (aged 8-12 weeks). Annexin V phycoerythrin/7-actinomycin D staining was used to evaluate BMSC and cardiomyocyte survival after exposure to hydrogen peroxide in vitro. B-cell lymphoma 2 (Bcl-2) protein expression was measured by flow cytometric and western blot analyses. The effects of MRTF-A-overexpressing BMSCs in a rat model of AMI were investigated by hematoxylin and eosin staining and western blot analysis of Bcl-2 expression in myocardial tissue sections. MRTF-A enhanced the migration of BMSCs, and overexpression of MRTF-A in BMSCs prevented hydrogen peroxide-induced apoptosis in primary cardiomyocytes ex vivo. In addition, co-culture of cardiomyocytes with MRTF-A-overexpressing BMSCs inhibited hydrogen peroxide induced apoptosis and the enhanced expression of Bcl-2. Furthermore, in vivo, enhanced cell survival was observed in the MRTF-A-modified BMSC group compared with that in the control group. These observations indicated that MRTF-A overexpressing BMSCs have the potential to exert cardioprotective effects against hydrogen peroxide-induced injury and that treatment with MRTF-A-modified BMSCs is able to reverse cardiac dysfunction after AMI. PMID- 26135209 TI - Despite High Cost, Improved Pneumococcal Vaccine Expected To Return 10-Year Net Savings Of $12 Billion. AB - In 2010 the US Advisory Committee on Immunization Practices recommended that the seven-valent pneumococcal conjugate vaccine (PCV7) be replaced by the thirteen valent version (PCV13), which provides protection against six additional serotypes of the bacterium Streptococcus pneumoniae. The higher price of PCV13, compared to PCV7, may be a concern for funding agencies and payers, as has been the case with other new vaccines. This study estimated the budgetary impact on both public and private US insurance payers of the routine use of PCV13 instead of PCV7 from 2010 to 2019. Implementing the PCV13 vaccine is projected to cost public and private payers $3.5 billion and $2.6 billion, respectively, more than PCV7. However, PCV13 is expected to provide net cost savings of $6.1 billion and $4.2 billion, respectively, to those payers during the ten-year period by preventing pneumococcal disease and its associated costs. An additional $1.7 billion in cost savings would be realized for uninsured patients, whose costs ultimately fall on those payers. Despite its higher price, compared to PCV7, this new vaccine is expected to provide payers with substantial net budgetary savings. PMID- 26135210 TI - Low back pain has a poor prognosis for recovery among seniors. PMID- 26135211 TI - Oral steroids for improved function but not pain in acute radiculopathy due to disc herniation. PMID- 26135213 TI - 6-Deoxy-6-aminoethyleneamino cellulose: synthesis and study of hemocompatibility. AB - Hemocompatibility of aqueous solutions of antimicrobial 6-deoxy-6 aminoethyleneamino (AEA) cellulose with different degrees of substitution (DS, 0.54-0.92) was investigated in vitro. The AEA cellulose derivatives were synthesized by tosylation of cellulose and subsequent nucleophilic substitution with 1,2-diaminoethane. The structure was confirmed by elemental analysis as well as by FTIR and NMR spectroscopies. Markers for coagulation (thrombin generation, aPTT, PT, blood clotting, thrombocyte activation) and membrane integrity (hemolysis) were measured in human whole blood, human platelet-rich plasma, human pooled plasma, and erythrocytes suspension. AEA cellulose with a low DS of 0.54 showed the highest hemocompatibility in vitro, suggesting the possibility of biomedical applications. PMID- 26135214 TI - Palladium-Catalyzed Intermolecular Oxyarylation of Vinylacetates with Retention of an Alkenyl Moiety. AB - Palladium-catalyzed intermolecular oxyarylation reaction of vinylacetates with retention of the double bond in the final product is developed. Under the optimized reaction conditions, the desired products of multisubstituted vinylesters could be obtained in moderate to high yields. PMID- 26135215 TI - Recurrent Abnormal Clones in Myelodysplastic Syndrome Marrow Originate from Cells at a Pluripotent Stem Level and Maintain Their Early Differentiation Potency. AB - OBJECTIVE: The present study aimed to investigate the origins and differentiation potencies of 4 common malignant clonal cell types (+8, 5q-/-5, 20q-/-20, 7q-/-7) in myelodysplastic syndrome (MDS) and to investigate whether the trisomy of chromosome 8 occurs subsequently to other chromosomal abnormalities. METHODS: The present study analyzed a total of 46 cases of chromosomal abnormalities in MDS patients. The magnetic activated cell sorting technique (MACS) was used to sort the CD34(+)CD38(-) (pluripotent hematopoietic stem cells) and CD34(+)CD38(+) cells (committed progenitor cells) from the bone marrow mononuclear cells (BMNCs) of these patients; the sorted cells were then individually smeared. Meanwhile, cytospins were prepared from the remaining CD34(-) BMNCs after cell sorting. The clonal cell proportions in these three types of smears were detected by fluorescence in situ hybridization (FISH). Cases in which +8 was associated with another abnormality (2 cases each in combination with abnormalities in chromosomes 7, 5, and 20) were dually hybridized with the cep8 probe and another corresponding probe. RESULTS: (1) for abnormalities of +8, 5q-/-5, 20q-/-20 or chromosome 7 involvements, clonal cells above the baseline level were detected in the pluripotent stem cell level. (2) The average clonal cell proportion in the committed progenitor cells of the 46 cases increased to 75.3% from 57.3% at the level of stem cell (p < 0.001). The groups with +8 and chromosome 5 abnormalities showed a statistically significant increase in clonal cells at the progenitor cell stage. At the individual level, 33 of 46 cases showed significant increases in clonal cells at the progenitor cell stage relative to the stem cell stage, whereas the clonal cell proportion in the CD34(-) BMNCs generally did not increase relative to the committed progenitor cell population. (3) The dual hybridization analysis showed that if +8 and another abnormality were present in the same abnormal clone according to G-banding, +8 always coexisted with the other chromosomal abnormality at the single cell level; there were no situations in which +8 occurred later than the other chromosomal abnormality. CONCLUSION: It seems that the all malignant MDS clones originated at the pluripotent hematopoietic stem cell stage and that the proliferation and differentiation potencies were retained partly in these clonal cells. The present study failed to confirm that the trisomy 8 occurred subsequently to the other abnormalities, but some in vitro or transplant experiments maybe prove the succession of clonal origination. PMID- 26135212 TI - CdiA promotes receptor-independent intercellular adhesion. AB - CdiB/CdiA proteins mediate inter-bacterial competition in a process termed contact-dependent growth inhibition (CDI). Filamentous CdiA exoproteins extend from CDI(+) cells and bind specific receptors to deliver toxins into susceptible target bacteria. CDI has also been implicated in auto-aggregation and biofilm formation in several species, but the contribution of CdiA-receptor interactions to these multi-cellular behaviors has not been examined. Using Escherichia coli isolate EC93 as a model, we show that cdiA and bamA receptor mutants are defective in biofilm formation, suggesting a prominent role for CdiA-BamA mediated cell-cell adhesion. However, CdiA also promotes auto-aggregation in a BamA-independent manner, indicating that the exoprotein possesses an additional adhesin activity. Cells must express CdiA in order to participate in BamA independent aggregates, suggesting that adhesion could be mediated by homotypic CdiA-CdiA interactions. The BamA-dependent and BamA-independent interaction domains map to distinct regions within the CdiA filament. Thus, CdiA orchestrates a collective behavior that is independent of its growth-inhibition activity. This adhesion should enable 'greenbeard' discrimination, in which genetically unrelated individuals cooperate with one another based on a single shared trait. This kind-selective social behavior could provide immediate fitness benefits to bacteria that acquire the systems through horizontal gene transfer. PMID- 26135216 TI - Theoretical Insight into Dispersion of Silica Nanoparticles in Polymer Melts. AB - Silica nanoparticles dispersed in polystyrene, poly(methyl methacrylate), and poly(ethylene oxide) melts have been investigated using a density functional approach. The polymers are regarded as coarse-grained semiflexible chains, and the segment sizes are represented by their Kuhn lengths. The particle-particle and particle-polymer interactions are calculated with the Hamaker theory to reflect the relationship between particles and polymer melts. The effects of particle volume fraction and size on the particle dispersion have been quantitatively determined to evaluate their dispersion/aggregation behavior in these polymer melts. It is shown that theoretical predictions are generally in good agreement with the corresponding experimental results, providing the reasonable verification of particle dispersion/agglomeration and polymer depletion. PMID- 26135217 TI - 26th International Conference of the Society for Medical Innovation and Technology (SMIT). PMID- 26135218 TI - When is the best time for temporary stoma closure in laparoscopic sphincter saving surgery for rectal cancer? A study of 259 consecutive patients. AB - BACKGROUND: There is no consensus regarding the best timing for temporary stoma closure after proctectomy for rectal cancer, especially if the patient requires adjuvant chemotherapy. This study aimed to assess whether the timing of stoma closure could influence postoperative morbidity. METHODS: Patients with rectal cancer undergoing laparoscopic proctectomy with temporary stoma were included and divided into three groups according to the delay of stoma closure after proctectomy: <=60 days (Group A), 61-90 days (Group B), and >90 days (Group C). RESULTS: From 2008 to 2013, 259 patients (146 men, median age 61 years) were divided into Groups A (n = 65), B (n = 115), and C (n = 79). At the time of stoma closure, seven (11%) patients received adjuvant chemotherapy in Group A versus 42 (37%) in Group B (p = 0.0002) and 24 (30%) in Group C (p = 0.004), and peristomal hernia was noted in four patients (6%) in Group A versus 14 (12%) in Group B and 21 (27%) in Group C (p < 0.0001). Although overall postoperative morbidity was similar between groups, anastomotic leakage (at the stoma closure site) was noted in one patient in Group A versus zero in Group B versus four in Group C (p = 0.03). Median hospital stay was 5 days in Group A versus 6 in Group B versus 6 in Group C (p = 0.004). CONCLUSIONS: Our results suggested that timing of temporary stoma closure can influence postoperative morbidity. Best results were obtained if stoma closure was performed before 90 days, even during adjuvant chemotherapy. There is no benefit in delaying stoma closure after completion of adjuvant chemotherapy. PMID- 26135219 TI - Viscosity Dependence of Some Protein and Enzyme Reaction Rates: Seventy-Five Years after Kramers. AB - Kramers rate theory is a milestone in chemical reaction research, but concerns regarding the basic understanding of condensed phase reaction rates of large molecules in viscous milieu persist. Experimental studies of Kramers theory rely on scaling reaction rates with inverse solvent viscosity, which is often equated with the bulk friction coefficient based on simple hydrodynamic relations. Apart from the difficulty of abstraction of the prefactor details from experimental data, it is not clear why the linearity of rate versus inverse viscosity, k ? eta(-1), deviates widely for many reactions studied. In most cases, the deviation simulates a power law k ? eta(-n), where the exponent n assumes fractional values. In rate-viscosity studies presented here, results for two reactions, unfolding of cytochrome c and cysteine protease activity of human ribosomal protein S4, show an exceedingly overdamped rate over a wide viscosity range, registering n values up to 2.4. Although the origin of this extraordinary reaction friction is not known at present, the results indicate that the viscosity exponent need not be bound by the 0-1 limit as generally suggested. For the third reaction studied here, thermal dissociation of CO from nativelike cytochrome c, the rate-viscosity behavior can be explained using Grote-Hynes theory of time-dependent friction in conjunction with correlated motions intrinsic to the protein. Analysis of the glycerol viscosity-dependent rate for the CO dissociation reaction in the presence of urea as the second variable shows that the protein stabilizing effect of subdenaturing amounts of urea is not affected by the bulk viscosity. It appears that a myriad of factors as diverse as parameter uncertainty due to the difficulty of knowing the exact reaction friction and both mode and consequences of protein-solvent interaction work in a complex manner to convey as though Kramers rate equation is not absolute. PMID- 26135220 TI - 3-Hydroxy-3-methylglutaryl-coenzyme A reductase modulator: toward age- and sex personalized medicine. AB - Cholesterol homeostasis maintenance is regulated by a cellular feedback system that senses cholesterol amount in cellular membranes. 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) plays a pivotal role in cholesterol metabolism as it is the key rate-limiting enzyme of its biosynthetic pathway; its inhibition provokes a feedback response capable of reducing plasma cholesterol content. HMGR inhibition is a keystone in the treatment and prevention of cardiovascular disease and, therefore, statins (HMGR inhibitors) are widely prescribed even though they may sometimes induce side effects. These drugs are prescribed indifferently to both man and women even if there are several well-known differences in cholesterol metabolism depending on the gender and the age. Thus, gender-related differences in cholesterol metabolism should be taken into account to identify new targets for customized pharmacological treatments for hypercholesterolemia. PMID- 26135221 TI - Expanding stroke telerehabilitation services to rural veterans: a qualitative study on patient experiences using the robotic stroke therapy delivery and monitoring system program. AB - PURPOSE: The present study reports on a robotic stroke therapy delivery and monitoring system intervention. The aims of this pilot implementation project were to determine participants' general impressions about the benefits and barriers of using robotic therapy devices for in-home rehabilitation. METHODS: We used a qualitative study design employing ethnographic-based anthropological methods including direct observation of the in-home environment and in-depth semi structured interviews with 10 users of the hand or foot robotic devices. Thematic analysis was conducted using an inductive approach. RESULTS: Participants reported positive experiences with the robotic stroke therapy delivery and monitoring system. Benefits included convenience, self-reported increased mobility, improved mood and an outlet for physical and mental tension and anxiety. Barriers to use were few and included difficulties with placing the device on the body, bulkiness of the monitor and modem connection problems. CONCLUSIONS: Telerehabilitation robotic devices can be used as a tool to extend effective, evidence-based and specialized rehabilitation services for upper and lower limb rehabilitation to rural Veterans with poor access to care. Implications for Rehabilitation Participants whose formal therapy services had ended either because they had exhausted their benefits or because traveling to outpatient therapy was too cumbersome due to distance were able to perform therapeutic activities in the home daily (or at least multiple times per week). Participants who were still receiving formal therapy services either in-home or in the clinic were able to perform therapeutic activities in the home on the days they were not attending/receiving formal therapy. Based on the feedback from these veterans and their caregivers, the manufacturing company is working on modifying the devices to be less cumbersome and more user-friendly (lighter weight, more mobile, changing software, etc.), as well as more adaptable to participants' homes. Removing these specific barriers will potentially allow participants to utilize the device more easily and more frequently. Since participants expressed that they wished they could have the device in their homes longer than the 3-month usage period required for this pilot project, the project team is working on a proposal to extend this project to a wider area and the new paradigm would extend the usage period until the patient reaches a plateau in progress or no longer wants to use the device. PMID- 26135222 TI - Interdisciplinary development of manual and automated product usability assessments for older adults with dementia: lessons learned. AB - The changes in cognitive abilities that accompany dementia can make it difficult to use everyday products that are required to complete activities of daily living. Products that are inherently more usable for people with dementia could facilitate independent activity completion, thus reducing the need for caregiver assistance. The objectives of this research were to: (1) gain an understanding of how water tap design impacted tap usability and (2) create an automated computerized tool that could assess tap usability. 27 older adults, who ranged from cognitively intact to advanced dementia, completed 1309 trials on five tap designs. Data were manually analyzed to investigate tap usability as well as used to develop an automated usability analysis tool. Researchers collaborated to modify existing techniques and to create novel ones to accomplish both goals. This paper presents lessons learned through the course of this research, which could be applicable in the development of other usability studies, automated vision-based assessments and the development of assistive technologies for cognitively impaired older adults. Collaborative interdisciplinary teamwork, which included older adult with dementia participants, was key to enabling innovative advances that achieved the projects' research goals. Implications for Rehabilitation Products that are implicitly familiar and usable by older adults could foster independent activity completion, potentially reducing reliance on a caregiver. The computer-based automated tool can significantly reduce the time and effort required to perform product usability analysis, making this type of analysis more feasible. Interdisciplinary collaboration can result in a more holistic understanding of assistive technology research challenges and enable innovative solutions. PMID- 26135223 TI - Slow dynamics of water confined in Newton black films. AB - Slowdown of translational and reorientational dynamics of water confined in Newton black films (NBFs) is revealed by molecular dynamics simulations. As a film becomes thinner, both translational and reorientational dynamics become slower. The polarization of water molecules in the macroscopic electrostatic field across the NBF and the coordination of Na(+) ions and surfactant anionic groups around water molecules concertedly lead to slowdown of water dynamics. The polarization effect is obvious for water not coordinated by Na(+) ions, which exhibits reorientational dynamics depending on initial dipole orientations. Na(+) ions and surfactant anionic groups retard dynamics of surrounding water by decreasing the hydrogen bond exchange probability and increasing the viscosity of water. The dependences of translational and reorientational dynamics on coordination environments of water are similar. Dynamics of water in positions close to the interfaces of NBFs are mainly retarded by Na(+) ions and surfactant anionic groups, while the macroscopic polarization effect plays the main role in influencing water dynamics in positions far from the interfaces. This study sheds light on the improvement of knowledge about the water dynamics slowdown mechanism in similar environments like reverse micelles and lamellar structures. PMID- 26135224 TI - Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis. AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tube placement is recommended in amyotrophic lateral sclerosis (ALS) patients with dysphagia to provide reliable access for medications and nutrition. It is preferably done while forced vital capacity (FVC) is greater than 50% of predicted to reduce risk of postprocedural respiratory complications. Percutaneous radiologic gastrostomy has been shown to have higher success rates and lower complication rates compared with PEG. The authors sought to investigate the safety of PEG placement in ALS patients with varying respiratory compromise. METHODS: The records of 21 patients with ALS who underwent PEG tube placement from October 2010 to October 2013 were retrospectively reviewed to determine rates of successful placement, complication, mortality and survival. RESULTS: PEG was placed successfully in 95.2% of patients. There was 1 major complication, procedure-related death, and failed placement in a patient with FVC 15% predicted who developed procedure related aspiration and hypoxic respiratory failure and death 8 days after failed PEG attempt. Minor complications included 3 patients with minor pain at insertion site, 1 patient with minor bleeding requiring cauterization and 2 patients requiring PEG tube replacement within 6 months of procedure for accidental dislodgement. After PEG placement, median survival was 327 days (95% confidence interval: 180-687). CONCLUSIONS: In conclusion, PEG tube placement in patients with ALS seems to be a safe procedure in patients without significant respiratory compromise. In patients with FVC <50%, based on literature review and the results of this study, the authors recommend percutaneous radiologic gastrostomy over PEG placement. PMID- 26135225 TI - Heart beats: not to be beaten. PMID- 26135226 TI - Reply to the letter from Kumar et al.: Maastricht experience with the second generation endoscopic laser balloon ablation system for the atrial fibrillation. PMID- 26135227 TI - Chorioamnionitis and neonatal outcome in preterm infants: a clinical overview. AB - The term chorioamnionitis is used to refer to an intrauterine infection/inflammation occurring between the maternal tissues and the fetal membranes (choriodecidual space) or in the fetal annexes (chorioamniotic membranes, amniotic fluid, umbilical cord). Histological examination of the placenta is the gold standard for diagnosis. However, clinical, biochemical and microbiological criteria are also used to define the disease. The literature contains a large body of evidence showing that chorioamnionitis is the leading cause of very preterm birth and, therefore, contributes significantly to neonatal morbidity and mortality. In recent decades, numerous studies have attempted to establish whether, and to what extent, intrauterine infection/inflammation might negatively affect the short- and long-term outcome of preterm infants. The question is still unanswered. The discrepancy observed across studies can be attributed largely to the use of different inclusion and exclusion criteria, diagnostic criteria and methods, and to whether or not potential confounding factors, such as gestational age were considered. Anyhow, the association between chorioamnionitis and severe prematurity requires serious efforts by researchers to clarify the mechanisms linking intrauterine infection/inflammation with preterm birth, and thus to identify strategies that may guide clinicians' diagnostic and therapeutic choices, with regard to both mothers and infants. PMID- 26135228 TI - Highly stretchable and mechanically stable transparent electrode based on composite of silver nanowires and polyurethane-urea. AB - Transparent electrodes based on conventional indium-tin oxide (ITO) can hardly meet the requirements of future generations of stretchable electronic devices, including artificial skins, stretchable displays, sensors, and actuators, because they cannot retain high conductivity under substantial stretching and bending deformation. Here we suggest a new approach for fabricating highly stretchable and transparent electrodes with good stability in environments where they would be stretched repeatedly. We designed polyurethane-urea (PUU), a urethane-based polymer, to enhance the adhesion between Ag nanowires (AgNWs) and poly(dimethylsiloxane) (PDMS). The adhesion could be further improved when irradiated by intense pulsed light (IPL). After delicate optimization of the layered AgNW/PUU/PDMS structure, we fabricated a stretchable transparent electrode that could withstand 100 cycles of 50% stretching-releasing, with exceptionally high stability and reversibility. This newly developed electrode is therefore expected to be directly applicable to a wide range of high-performance, low-cost, stretchable electronic devices. PMID- 26135229 TI - In Vivo Biomolecule Corona around Blood-Circulating, Clinically Used and Antibody Targeted Lipid Bilayer Nanoscale Vesicles. AB - The adsorption of proteins and their layering onto nanoparticle surfaces has been called the "protein corona". This dynamic process of protein adsorption has been extensively studied following in vitro incubation of many different nanoparticles with plasma proteins. However, the formation of protein corona under dynamic, in vivo conditions remains largely unexplored. Extrapolation of in vitro formed protein coronas to predict the fate and possible toxicological burden from nanoparticles in vivo is of great interest. However, complete lack of such direct comparisons for clinically used nanoparticles makes the study of in vitro and in vivo formed protein coronas of great importance. Our aim was to study the in vivo protein corona formed onto intravenously injected, clinically used liposomes, based on the composition of the PEGylated liposomal formulation that constitutes the anticancer agent Doxil. The formation of in vivo protein corona was determined after the recovery of the liposomes from the blood circulation of CD-1 mice 10 min postinjection. In comparison, in vitro protein corona was formed by the incubation of liposomes in CD-1 mouse plasma. In vivo and in vitro formed protein coronas were compared in terms of morphology, composition and cellular internalization. The protein coronas on bare (non-PEGylated) and monoclonal antibody (IgG) targeted liposomes of the same lipid composition were also comparatively investigated. A network of linear fibrillary structures constituted the in vitro formed protein corona, whereas the in vivo corona had a different morphology but did not appear to coat the liposome surface entirely. Even though the total amount of protein attached on circulating liposomes correlated with that observed from in vitro incubations, the variety of molecular species in the in vivo corona were considerably wider. Both in vitro and in vivo formed protein coronas were found to significantly reduce receptor binding and cellular internalization of antibody-conjugated liposomes; however, the in vivo corona formation did not lead to complete ablation of their targeting capability. PMID- 26135230 TI - Formulation development and systematic optimization of stabilized ziprasidone hydrochloride capsules devoid of any food effect. AB - CONTEXT AND OBJECTIVE: The objective of the study was to develop a stable capsule formulation of ziprasidone hydrochloride which can be administered without regards to food intake. MATERIALS AND METHODS: The unstable anhydrous form of ziprasidone hydrochloride was stabilized employing hot-melt extrusion and further optimized by 32 central composite design. The formulation was optimized after establishing acceptable ranges for response variables like disintegration time, dissolution and impurity profile. A crossover fasted and fed in vivo study was conducted in human volunteers to assess the food-effect of optimized formulation vis-a-vis the marketed brand. RESULTS AND DISCUSSION: The optimized formulation met in-house specifications for various response variables. Further, high values of correlation coefficient vouch the adequate selection of experimental design and its high prognostic ability. In our study, no significant difference was observed between the Cmax and AUC values after administration of the optimized formulation in fasted and fed states. On the contrary, there was a statistically significant increase in the Cmax and AUC values after oral administration of Zeldox in fed state in comparison to fasted state. CONCLUSIONS: The present study describes the successful development of a stable formulation of 20 mg of ziprasidone devoid of any food-effects. PMID- 26135231 TI - Usnea barbata CO2-supercritical extract in alkyl polyglucoside-based emulsion system: contribution of Confocal Raman imaging to the formulation development of a natural product. AB - Topical treatment of skin infections is often limited by drawbacks related to both antimicrobial agents and their vehicles. In addition, considering the growing promotion of natural therapeutic products, our objective was to develop and evaluate naturally-based emulsion system, as prospective topical formulation for skin infections-treatment. Therefore, alkyl polyglucoside surfactants were used for stabilization of a vehicle serving as potential carrier for supercritical CO2-extract of Usnea barbata, lichen with well-documented antimicrobial activity, incorporated using two protocols and three concentrations. Comprehensive physicochemical characterization suggested possible involvement of extract's particles in stabilization of the investigated system. Raman spectral imaging served as the key method in disclosing extract's particles potential to participate in the microstructure of the tested emulsion system via three mechanisms: (1) particle-particle aggregation, (2) adsorption at the oil water interface and (3) hydrophobic particle-surfactant interactions. Stated extract-vehicle interaction proved to be correlated to the preparation procedure and extract concentration on one hand and to affect the physicochemical and biopharmaceutical features of investigated system, on the other hand. Thereafter, formulation with the best preliminary stability and liberation profile was selected for further efficiency and in vivo skin irritation potential evaluation, implying pertinent in vitro antimicrobial activity against G+ bacteria and overall satisfying preliminary safety profile. PMID- 26135232 TI - The influence of the tongue on dentofacial growth. PMID- 26135233 TI - Re: The premature loss of primary first molars: space loss to molar occlusal relationships and facial patterns by Stanley A. Alexander, Marjan Askari, Patricia Lewis. Angle Orthod. 2015 Mar;85(2): 218-223. PMID- 26135234 TI - Re: Response to: The premature loss of primary first molars: space loss to molar occlusal relationships and facial patterns by Stanley A. Alexander, Marjan Askari, Patricia Lewis. Angle Orthod. 2015 Mar;85(2):218-223. PMID- 26135236 TI - Neighborhood socioeconomic status and self-rated health in Israel: the Israel National Health Interview Survey. AB - OBJECTIVES: To explore neighborhood socioeconomic status (NSES) differentials in self-rated health (SRH) in Israel. METHODS: Study sample included 6296 Jewish participants in the Israeli National Health Interview Survey of 2007-2008. Neighborhoods were assigned socioeconomic scores by the Central Bureau of Statistics, incorporating 16 demographic and socioeconomic measures using a 20 point scale. Generalized estimating equation models with a multinomial distribution assessed the relative cumulative odds for decreasing SRH by quartiles of NSES, while accounting for neighborhood clustering. Base models were adjusted for age, religiosity, immigration from the former Soviet Union, education, income, and then additionally for employment, living in the periphery and co-morbidity. RESULTS: We found a strong association between poor SRH and living in disadvantaged neighborhoods, after adjusting for individual-level SES. The combination of living in deprived areas with below average income was associated with over twice the risk of poor SRH. CONCLUSIONS: The association between low NSES and worsening SRH, exacerbated by lower income, highlights the importance of considering socioeconomic environmental and individual conditions in targeting high-risk populations. PMID- 26135237 TI - Global health and environmental pollution. PMID- 26135238 TI - Climate change: an opportunity for health promotion practitioners? PMID- 26135239 TI - Google Flu Trends in Canada: a comparison of digital disease surveillance data with physician consultations and respiratory virus surveillance data, 2010-2014. AB - The value of Google Flu Trends (GFT) remains unclear after it overestimated the proportion of physician visits related to influenza-like illness (ILI) in the United States in 2012-2013. However, GFT estimates (%GFT) have not been examined nationally in Canada nor compared with positivity for respiratory viruses other than influenza. For 2010-2014, we compared %GFT for Canada to Public Health Agency of Canada ILI consultation rates (%PHAC) and to positivity for influenza A and B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and rhinoviruses. %GFT correlated well with %PHAC (rho = 0.77-0.90) and influenza A positivity (rho = 0.64-0.96) and overestimated the 2012-2013 %PHAC peak by 0.99 percentage points. %GFT peaks corresponded temporally with peaks in positivity for influenza A and rhinoviruses (all seasons) and RSV and hMPV when their peaks preceded influenza peaks. In Canada, %GFT represented traditional surveillance data and corresponded temporally with patterns in circulating respiratory viruses. PMID- 26135240 TI - Mechanically Tough Large-Area Hierarchical Porous Graphene Films for High Performance Flexible Supercapacitor Applications. AB - Mechanically tough large-area hierarchical porous graphene films are fabricated by blade-casting of graphene oxide hydrogel and postcasting reduction. The as prepared graphene films, which consist of well-exfoliated graphene nanosheets, possess interpenetrating 3D hierarchical porous structures, high strength and modulus, large specific area, and high electrical conductivity. Flexible film supercapacitors fabricated with the graphene electrodes show superior areal capacitance, good rate performance, and excellent mechanical stability. PMID- 26135241 TI - Insecticidal potential of Ocimum canum plant extracts against Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus larval and adult mosquitoes (Diptera: Culicidae). AB - Mosquitoes have developed resistance to various synthetic insecticides, making their control increasingly difficult. Insecticides of botanical origin may serve as suitable natural control. This study evaluates the toxic potential of Ocimum canum (Sims) leaf extract and powder against Anopheles stephensi (Liston), Aedes aegypti (Lin) and Culex quinquefasciatus (Say) larval and adult mosquitoes. Larval mortality was observed after 24 h recovery period and adult smoke toxicity observed for 40 min duration at 10 min interval. Methanol extract of O. canum showed highest larval mortality against the larvae of C. quinquefasciatus LC50 = 28.3225, LC90 = 44.1150; Ae. aegypti LC50 = 43.327, LC90 = 61.249; and An. stephensi LC50 = 30.2001, LC90 = 48.2866 ppm. The smoke toxicities were 93% mortality in C. quinquefasciatus, 74% in Ae. aegypti and 79% in An. stephensi adults, respectively, whereas 100% mortality was recorded in the commercial mosquito control. Our results suggest that O. canum leaf extract and powder are natural insecticide, and ideal eco friendly approach for mosquito control. PMID- 26135242 TI - Box, cable and smartphone: a simple laparoscopic trainer. AB - BACKGROUND: Laparoscopic surgery requires different abilities to open surgery, and is challenging to learn within the confines of the operating theatre. With the development of laparoscopic surgery in modern surgery, the importance in improving these skills is becoming an increasing focus of surgical training programmes. CONTEXT: The assembly of the laparoscopic trainer and exercises was performed at the University of Sydney Clinical School located at Hornsby Hospital in Sydney, Australia. The objective was to design and construct a new concept smartphone box laparoscopic trainer that is affordable and replicable, and to demonstrate its usefulness in practising laparoscopic techniques to improve skills outside of the operating theatre. INNOVATION: The trainer was constructed using a personal smartphone, cardboard box, video graphics array (VGA) adaptor, VGA cable and a computer screen. Laparoscopic instruments and materials used for simulated task exercises were obtained from the operating theatre. Simulated demonstrations of simple laparoscopic tasks included suture handling, instrument knot-tying and anastomotic suture techniques. IMPLICATIONS: The smartphone box trainer is inexpensive (approximately $60) and took less than 20 minutes to build. The cost was almost entirely for the VGA adaptor. The box trainer was light, portable and easily transported to any setting that provided a computer screen. It is an inexpensive, easy-to-assemble, replicable model that benefits from the advanced technology of personal smartphones, and can be easily accessed as a useful tool in learning and improving laparoscopic techniques. Laparoscopic surgery requires different abilities to open surgery. PMID- 26135243 TI - Self-Perceived Peer Acceptance in Preschoolers of Differing Economic and Cultural Backgrounds. AB - Self-evaluation begins in early childhood and becomes more nuanced as children get older. However, little is known about the specific factors that predict self perception and in particular peer acceptance, early in life. This is especially true for low-income children and children of different ethnicities. This study examined 4-year-old children's feelings of social acceptance relative to teachers' perceptions. It also explored whether temperament, language skills, traditional parenting, and teachers' perceptions of peer acceptance were related to children's self-perceptions. Using 94 preschoolers from different cultural and economic backgrounds as participants, results of a mixed model analysis of variance indicated that the relation between children's self-perceptions and teachers' ratings were not uniform across economic and cultural groups. In addition, results of hierarchical multiple regression analyses demonstrated that traditional parenting was one of the strongest predictors of children's social self-perceptions. Beyond parenting, children with relatively good verbal skills, who were not temperamentally shy, tended to perceive themselves as socially competent. PMID- 26135244 TI - Valuing Child Health Utility 9D Health States with Young Adults: Insights from a Time Trade Off Study. AB - OBJECTIVES: In contrast to the proliferation of studies incorporating health state values from adults of all ages, relatively few studies have reported upon the application of the time trade off (TTO) approach to generate health state values from populations of younger adults. This study sought to employ a conventional TTO approach to obtain values for a selection of Child Health Utility 9D (CHU9D) health states from a sample of young adults aged 18-29 years and to compare with the values generated from application of the original UK adult standard gamble scoring algorithm and the Australian adolescent scoring algorithm. METHODS: A convenience sample of Flinders University undergraduate students aged 18-29 years were invited to participate in an interviewer administered conventional TTO task to value a series of five CHU9D health impairment states using the widely used variant developed by the York EQ-5D team. RESULTS: A total of 152 students within the target age range were approached to participate in the study of whom n = 38 consented to participate, giving an overall participation rate of 25%. With the exception of one health state, the mean TTO values were consistently lower than those generated from application of the original scoring algorithm for the CHU9D elicited with adults of all ages. A significant proportion of participants (n = 17, 45%) considered the most severe CHU9D (PITS) state to be worse than death. CONCLUSIONS: This study adds to a growing body of evidence indicating that the values attached to identical health states are typically lower for younger people in comparison with adults of all ages and dependent upon the elicitation method utilised. The values obtained are applicable for re-scaling raw CHU9D health state values obtained from younger adolescent samples using profile case best-worst scaling. PMID- 26135245 TI - Persistence of Meningococcal Antibodies and Response to a Third Dose After a Two dose Vaccination Series with Investigational MenABCWY Vaccine Formulations in Adolescents. AB - BACKGROUND: In a primary study, healthy adolescents received 2 doses (months 0/2) of 1 of the 4 investigational meningococcal ABCWY vaccine formulations, containing components of licensed quadrivalent glycoconjugate vaccine MenACWY CRM, combined with different amounts of recombinant proteins (rMenB) and outer membrane vesicles (OMV) from a licensed serogroup B vaccine, or 2 doses of rMenB alone or 1 dose of MenACWY-CRM then a placebo. METHODS: This phase 2 extension study evaluated antibody persistence up to 10 months after the 2-dose series and the immunogenicity and safety of a third dose (month 6). Immune responses against serogroups ACWY and serogroup B test strains were measured by serum bactericidal assay with human complement. RESULTS: At month 12, antibody persistence against serogroups ACWY in all 2-dose MenABCWY groups was at least comparable with the 1 dose MenACWY-CRM group. Bactericidal antibodies against most serogroup B test strains declined by month 6, then plateaued over the subsequent 6 months, with overall higher antibody persistence associated with OMV-containing formulations. A third MenABCWY vaccine dose induced robust immune responses against vaccine antigens, although antibody levels 6 months later were comparable with those observed 5 months after the 2-dose series. All investigational MenABCWY vaccines were well tolerated. CONCLUSIONS: Two or three doses of investigational MenABCWY vaccines elicited immune responses against serogroups ACWY that were at least comparable with those after 1 dose of MenACWY-CRM. After either vaccination series, investigational MenABCWY vaccine formulations containing OMV had the highest immunogenicity against most serogroup B test strains. No safety concerns were identified in this study. PMID- 26135246 TI - Confirmation of Host Genetic Determinants in the CFH Region and Susceptibility to Meningococcal Disease in a Central European Study Sample. AB - BACKGROUND: Invasive meningococcal disease (IMD) is a leading cause of meningitis and severe sepsis in children and adolescents. Genetic factors are important in determining the susceptibility to and outcome of IMD. Recently, a genome-wide association study from the United Kingdom showed significant associations of single-nucleotide polymorphisms within complement factor H (CFH; rs1065489) and in CFH-related protein 3 (rs426736) with susceptibility of IMD. We report data of a genetic replication study in Central European children. METHODS: The study was conducted as a retrospective case-reference study involving 248 patients with confirmed diagnosis of IMD from Austria and Germany and 835 healthy reference individuals from a multicenter German birth cohort. RESULTS: Carriers of the minor alleles of rs1065489 and rs426736 were at lower risk of IMD [allelic odds ratio = 0.60 (0.44-0.82); P = 0.001 and 0.61 (0.45-0.83); P = 0.001]. Also, 2 major haplotypes (GT and TC) derived from the 2 single-nucleotide polymorphisms were significantly associated with IMD (P = 0.001 and P = 0.003, respectively). CONCLUSIONS: The consistency of the results between the genome-wide association study and our study population strengthens the association of CFH polymorphisms to the susceptibility of IMD. Our results support the conclusion that CFH is a critical determinant in acquiring meningococcal disease. PMID- 26135248 TI - Gene dosage reductions of Trf1 and/or Tin2 induce telomere DNA damage and lymphoma formation in aging mice. PMID- 26135247 TI - Structure of Hepatitis C Virus Envelope Glycoprotein E1 Antigenic Site 314-324 in Complex with Antibody IGH526. AB - Hepatitis C virus (HCV) is a positive-strand RNA virus within the Flaviviridae family. The viral "spike" of HCV is formed by two envelope glycoproteins, E1 and E2, which together mediate viral entry by engaging host receptors and undergoing conformational changes to facilitate membrane fusion. While E2 can be readily produced in the absence of E1, E1 cannot be expressed without E2 and few reagents, including monoclonal antibodies (mAbs), are available for study of this essential HCV glycoprotein. A human mAb to E1, IGH526, was previously reported to cross-neutralize different HCV isolates, and therefore, we sought to further characterize the IGH526 neutralizing epitope to obtain information for vaccine design. We found that mAb IGH526 bound to a discontinuous epitope, but with a major component corresponding to E1 residues 314-324. The crystal structure of IGH526 Fab with this E1 glycopeptide at 1.75A resolution revealed that the antibody binds to one face of an alpha-helical peptide. Single mutations on the helix substantially lowered IGH526 binding but did not affect neutralization, indicating either that multiple mutations are required or that additional regions are recognized by the antibody in the context of the membrane-associated envelope oligomer. Molecular dynamics simulations indicate that the free peptide is flexible in solution, suggesting that it requires stabilization for use as a candidate vaccine immunogen. PMID- 26135250 TI - Emergence and mobility of monopoles in a unidirectional arrangement of magnetic nanoislands. AB - Magnetricity, the magnetic equivalent of electricity, was recently verified experimentally for the first time. Indeed, like the stream of electric charges that produces electric current, emergent magnetic monopoles have been observed to roam freely in geometrically frustrated magnets known as spin ice. However, such phenomena demand extreme physical conditions, say, a single spin ice crystal has to be cooled to very low temperature, around 0.36 K. Candidates to overcome this difficulty are their artificial analogues, the so-called artificial spin ices. Here, we demonstrate that a specific unidirectional arrangement of nanoislands yields a peculiar system where magnetic monopoles emerge and are constrained to move along aligned dipoles, providing an ordered flow of magnetic charges at room temperature. PMID- 26135249 TI - Effects of Wnt/beta-catenin signaling on bisphenol A exposure in male mouse reproductive cells. AB - Bisphenol A (BPA) is a chemical used in numerous consumer products that is able to interfere with the mammalian endocrine system. The aim of the present study was to investigate the effects of BPA on male mouse reproductive cells following prenatal to postnatal exposure. In addition, the influence of BPA was detected on the expression levels of beta-catenin and dickkopf WNT signaling pathway inhibitor 1 (DKK-1) during the differentiation of spermatogenic cells in the mouse testes. beta-catenin and DKK-1 are two important proteins of the Wnt/beta catenin signaling pathway. On gestational day 1, pregnant ICR mice were randomly divided into four groups: A dimethyl sulfoxide group, and three groups treated with various concentrations of BPA (0.5, 10, and 50 ug/kg). BPA was administered from gestational day 1 to weaning on postnatal day (PND) 42. The number of murine pups and the male:female ratio was recorded for each group. On PND 42, the male pups were sacrificed and their wet weights and testicular coefficients were measured. Immunohistochemical and western blot analyses were used to detect the protein expression of beta-catenin and DKK-1 in the testicular tissue samples of the six-week-old male mice. The results indicated that the number of murine pups, as well as the testicular viscera coefficient of the male mice, significantly decreased in the BPA-treated groups, as compared with the control group (P<0.05, P<0.01); however, no significant difference was observed in the male/female ratio in the BPA-treated groups, as compared with the control group (P>0.05). The results from the immunohistochemical and western blot analyses indicated that the protein expression of beta-catenin and DKK-1 were significantly increased in the BPA-treated groups, as compared with the control group, and the distribution of spermospore and Leydig cells also increased in the testes. These results suggest that high expression levels of beta-catenin and DKK-1 may participate in BPA induced pathogenesis in male mouse reproductive cells. PMID- 26135251 TI - Controlling single-molecule junction conductance by molecular interactions. AB - For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak pi-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment. PMID- 26135253 TI - Calling for qualitative health studies. PMID- 26135252 TI - Treatment and Management of Dementia Due to Alzheimer's Disease. AB - OPINION STATEMENT: Alzheimer's disease (AD) is a progressive neurological disorder typically associated with episodic memory loss as the initial symptom, but individuals <65 years old may present with executive dysfunction, word finding difficulties, or visual processing deficits. In those with AD, curative treatments are not available, but there are interventions which may modify disease course, symptom appearance and severity, enhance quality of life for patient and caregivers, and maintain safety. Both pharmacological and non pharmacological interventions are important. PMID- 26135254 TI - Patient-posture and Ileal-intubation during colonoscopy (PIC): a randomized controlled open-label trial. AB - BACKGROUND AND AIMS: Patient's posture change is commonly employed by a colonoscopist to achieve complete examination. We studied whether patient's posture (left-lateral decubitus vs supine) influenced the success rate of ileal intubation. PATIENTS AND METHODS: In this prospective open-label randomized study performed in the Endoscopy Suite of a tertiary-care center, all adult outpatients referred for colonoscopy, in whom cecal intubation was achieved and who satisfied predefined inclusion criteria, were randomized to undergo ileal intubation in either of the above two postures. Colonoscopy (EC-201 WL, Fujinon) was performed after overnight poly-ethylene-glycol preparation, under conscious sedation and continuous pulse-oxymetry monitoring. After confirming cecal intubation, patients were randomized for ileal intubation. Success was defined by visualization of ileal mucosa or villi (confirmed by digital photography) and was attempted until limited by pain and/or time of >= 6 min. RESULTS: Of 320 eligible patients, 217 patients (150 males) were randomized, 106 to left-lateral decubitus and 111 to supine posture. At baseline, the two groups were evenly matched. Successful ileal intubation was achieved in 145 (66.8 %) patients overall, significantly higher in the supine posture (74.8 % versus 58.5 %; P = 0.014). On multivariate analysis, supine posture (P = 0.02), average/good right-colon preparation (P < 0.01), non thin-lipped ileocecal (IC) valve (P < 0.001) and younger age (P = 0.02) were independent predictors of success. Positive ileal findings were recorded in 13 (9 %) patients. CONCLUSION: Ileoscopy is more successful in supine than in left lateral decubitus posture. Age, bowel preparation and type of IC valve also determine success. PMID- 26135257 TI - Intraductal biliary polypectomy performed with a nasogastroscope. PMID- 26135255 TI - A new endoscopic closure method for gastric mucosal defects: feasibility of endoscopic hand suturing in an ex vivo porcine model (with video). AB - BACKGROUND AND STUDY AIMS: More secure endoscopic closure techniques for iatrogenic gastric defects are required for safe endoscopic surgery. We developed a novel endoscopic suturing method, endoscopic hand suturing (EHS), of gastric mucosal defects and determined its feasibility and efficacy ex vivo. MATERIALS AND METHODS: We created 24 mucosal defects (each 2 cm in diameter) by endoscopic submucosal dissection. The following three techniques were tested: EHS with a 3 - 0 barbed suture that was grasped with biopsy forceps (n = 6) or a prototype through-the-scope needle holder (n = 6) by endoscopy, looping with endoloops (n = 6) by endoscopy, and clipping with hemoclips (n = 6) by hand. The mucosal edges were attached to each other at three points. The closure strength was compared among the three groups, and the procedural duration was compared between the EHS and looping groups. RESULTS: All 12 lesions were completely closed by EHS. The median strength of the closure, measured with a spring scale, was significantly greater in the EHS group (0.74 kg) than in the looping group (0.33 kg, P = 0.0012) or clipping group (0.07 kg, P = 0.0009). The median procedural duration did not significantly differ between the EHS and looping groups (19.7 vs. 19.8 minutes, P = 1.0000). The use of the needle holder significantly reduced the procedural duration compared with the biopsy forceps. CONCLUSION: Mucosal defects can be firmly closed with EHS, which may be helpful for establishing a safer and more secure endoscopic surgery. PMID- 26135256 TI - Flexible platforms for natural orifice transluminal and endoluminal surgery. AB - The flexible endoscope is playing an increasingly pivotal role in minimally invasive transluminal and endoluminal surgery. Whilst the flexible nature of the platform is desirable in order to navigate through the abdominal cavity or through a lumen, there are a number of issues with using the platform for this purpose. The challenges associated with using flexible endoscopes such as a lack of triangulation of instruments and force transmission, which is often inadequate for endoscopic surgery are discussed in this review. As a result of these difficulties, a number of mechanically and robotically driven devices based upon the flexible endoscope are emerging. The design of these devices and potential problems are also reviewed. Finally, future robotic systems which are still in the development and validation stage are briefly discussed. The field of gastroenterology is diverging. The narrowing divide between minimally invasive and endoluminal surgery has led to a surge of innovative and novel devices which may in the future enable precise, seamless and scar less surgery. PMID- 26135258 TI - Foreword. PMID- 26135259 TI - How commonly is upper gastrointestinal cancer missed at endoscopy? A meta analysis. AB - BACKGROUND AND STUDY AIMS: Upper gastrointestinal (UGI) cancer in the Western world usually presents at an advanced stage, when opportunities for curative therapy are limited. The failure to detect subtle, early-stage UGI cancer at endoscopy may contribute to a poor prognosis. We undertook a meta-analysis of studies of endoscopic miss rates for UGI cancer to quantify how often opportunities to diagnose cancer at an earlier stage are missed. PATIENTS AND METHODS: A MEDLINE search was conducted to identify relevant studies, and a meta analysis was conducted. "Missed" UGI cancer was defined as cancer that had not been diagnosed by UGI endoscopy performed within 3 years before the diagnosis. Random effects meta-analysis was used to determine the event rate of missed UGI cancer. RESULTS: Ten studies were identified that included 3,787 patients with UGI cancer. Four hundred eighty-seven UGI cancers were missed at endoscopy within 3 years before diagnosis. Marked heterogeneity was observed between studies (I (2), 94.4 %; P < 0.001). On random effects meta-analysis, the pooled miss rates were 6.4 % (95 % confidence interval [CI], 4.3 % - 9.5 %) within 1 year and 11.3 % (95 % CI, 7.5 % - 16.6 %) within 3 years before diagnosis. There appeared to be no difference between the miss rates of oesophageal (44 %) and gastric (51 %) cancer (P = 0.42). Conclusion It appears that 11.3 % of UGI cancers are missed at endoscopy up to 3 years before diagnosis. To ameliorate the poor prognosis of patients with UGI cancer in the Western world, efforts should be made to improve the quality of UGI endoscopy and create opportunities for earlier diagnosis. PMID- 26135260 TI - l-Menthol sprayed on gastric mucosa causes edematous change. AB - BACKGROUND AND STUDY AIMS: l-Menthol (LM), sprayed on the distal gastric mucosa, is a safe antispasmodic agent used during esophagogastroduodenoscopy (EGD). However, it seems to affect gastric mucosal endoscopic findings. Therefore, we evaluated whether LM causes specific changes and impacts the endoscopic morphology of gastric lesions. PATIENTS AND METHODS: A total of 98 patients scheduled to undergo EGD were randomly assigned to receive LM solution (160 mg of 0.8 % LM added to 2.5 mL of indigo carmine [IC]; n = 49; LM group) or decuple diluted IC solution without LM (n = 49; placebo group). We compared the incidence of specific mucosal changes and the difference in the endoscopic findings of several gastric lesions between these groups. RESULTS: Annular-reticular - like mucosal changes appeared immediately after the administration of LM solution. This change was observed in 71.4 % of the LM group compared with 12.2 % of the placebo group (P < 0.01). In the placebo group, this change was observed in 14.7 % of subjects with atrophic gastritis compared with 6.7 % of those without atrophic gastritis (P = 0.39), whereas in the LM group, this change was observed in 84.8 % of subjects with atrophic gastritis compared with 43.8 % of those without atrophic gastritis (P < 0.01). Most early gastric cancers, erosions, and ulcers observed in this study became well demarcated after LM administration, although the incidence of gastric lesions did not differ significantly between the two groups. CONCLUSION: LM changes the gastric mucosa into edematous mucosa, and this occurs more frequently in atrophic gastric mucosa than in pathologic lesions. LM may facilitate the demarcation of pathologic gastric lesions without intestinal metaplasia. PMID- 26135261 TI - EMR is not inferior to ESD for early Barrett's and EGJ neoplasia: An extensive review on outcome, recurrence and complication rates. AB - Background and study aims In recent years, it has been reported that early Barrett's and esophagogastric junction (EGJ) neoplasia can be effectively and safely treated using endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Multiband mucosectomy (MBM) appears to be the safest EMR method. The aim of this systematic review is to assess the safety and efficacy of MBM compared with ESD for the treatment of early neoplasia in Barrett's or at the EGJ. Methods A literature review of studies published up to May 2013 on EMR and ESD for early Barrett's esophagus (BE) neoplasia and adenocarcinoma at the EGJ was performed through MEDLINE, EMBASE and the Cochrane Library. Results on outcome parameters such as number of curative resections, complications and procedure times are compared and reported. Results A total of 16 studies met the inclusion criteria for analysis in this study. There were no significant differences in recurrence rates when comparing EMR (10/380, 2.6 %) to ESD (1/333, 0.7 %) (OR 8.55; 95 %CI, 0.91 - 80.0, P = 0.06). All recurrences after EMR were treated with additional endoscopic resection. The risks of delayed bleeding, perforation and stricture rates in both groups were similar. The procedure was considerably less time-consuming in the EMR group (mean time 36.7 min, 95 %CI, 34.5 - 38.9) than in the ESD group (mean time 83.3 min, 95 %CI, 57.4 - 109.2). Conclusions The MBM technique for EMR is as effective as ESD when comparing outcomes related to recurrence and complication rates for the treatment of early Barrett's or EGJ neoplasia. The MBM technique is considerably less time consuming. PMID- 26135262 TI - Endoscopic submucosal dissection (ESD): still a matter for debate or a gold standard technique in both Western and Eastern countries? PMID- 26135263 TI - Gastric antral vascular ectasia: the evolution of therapeutic modalities. AB - Gastric Antral Vascular Ectasia (GAVE) may be an enigmatic source of non-variceal upper GI bleeding associated with various systemic diseases such as connective tissue disorders, liver disease, and chronic renal failure. Successful treatment of GAVE continues to be a challenge and has evolved through the years. Currently, given the rapid response, safety, and efficacy, endoscopic ablative modalities have largely usurped medical treatments as first-line therapy, particularly using argon plasma coagulation. However, other newer ablative modalities such as radiofrequency ablation, cryotherapy, and band ligations are promising. This paper is an overview of GAVE and its various endoscopic and medical therapies. PMID- 26135264 TI - Use of glasgow-blatchford bleeding score reduces hospital stay duration and costs for patients with low-risk upper GI bleeding. AB - BACKGROUND AND STUDY AIMS: Upper gastrointestinal (UGI) bleeding is a frequent cause of hospitalization. Its severity may be assessed before endoscopy using the Glasgow-Blatchford Bleeding Score (GBS), a score validated to identify patients requiring clinical intervention. The aim of this study was to assess whether the GBS was effective for shortening hospital stay and reducing costs in patients with an UGI bleeding predicted at low risk of requiring clinical intervention. PATIENTS AND METHODS: Consecutive outpatients presenting with UGI bleeding at our hospital were prospectively included. In the observational study phase, UGI endoscopy was performed in all patients according to routine clinical practice. In the interventional study phase, patients with a GBS of 0 were discharged with an appointment for an outpatient UGI endoscopy. All patients had follow-up at 7 and 30 days. Need for clinical intervention was defined as performance of endoscopic hemostasis, blood transfusion or surgery. Results Two-hundred and eight patients were included, 104 in each study phase; complete follow-up was obtained in 201 patients. GBS varied from 0 to 18, with 15 (14 %) and 11 (11 %) patients having a GBS of 0 in the observational and interventional study phase, respectively. For patients with a GBS of 0, hospital stay was shorter (6 versus 19 h, P < 0.01), and costs were lower (845 EUR versus 1272 EUR, P = 0.002) in the interventional versus the observational study phase. For patients with a GBS > 0, hospital stay duration did not significantly differ between study phases (189 versus 207 h, P = 0.726). No adverse event was observed in the patients sent home with a GBS of 0 during the interventional study phase. Conclusions Implementing the GBS as a tool for triage of hospital outpatients who present with UGI bleeding allowed us to identify those who could safely be discharged for ambulatory management. Implementing this change in the hospital strategy significantly shortened hospital stay and decreased management costs. PMID- 26135265 TI - Clinical utility of capsule endoscopy with flexible spectral imaging color enhancement for diagnosis of small bowel lesions. AB - BACKGROUND AND STUDY AIMS: The clinical utility of computed virtual chromoendoscopy with flexible spectral imaging color enhancement (FICE) in capsule endoscopy (CE) remains controversial. To clarify the clinical utility of FICE-enhanced CE in evaluating small bowel lesions, we quantitatively assessed white light (WL), FICE, and blue mode (BM) images and examined the sensitivity of these 3 imaging modes of small-bowel lesions from patients who underwent CE. METHODS: The CIELAB color difference (?E) and visual analogue scales (VAS) were measured in 261 CE images (3 different lesion categories) using WL and FICE set 1, 2, and 3, and BM images, respectively. Three endoscopists reviewed CE videos with WL, 3 FICE mode settings, and BM, and compared the sensitivity and detectability for small intestinal diseases from 50 patients who underwent CE. RESULTS: In the assessment of visibility in the 152 vascular lesion images, the ?E and VAS of FICE set 1, 2, and BM images were significantly higher than that of WL images. In 88 erosion/ulceration images, the ?E and VAS of FICE set 1 and 2 images were significantly higher than that of WL images. In 21 tumor images, there were no significant differences in ?E among these modalities. When analyzed on a per-patient basis, FICE settings 1 and 2 had the highest sensitivity (100 %) and specificity (97.3 - 100 %) for vascular lesions. As for erosive/ulcerative lesions, FICE setting 2 had the highest sensitivity (100 %) and specificity (97.2 %). For tumors or polyps, WL had the highest sensitivity (90.9 %) and specificity (87.1 %). In per-lesion analysis, FICE settings 1 and 2 showed significantly superior detection ability over WL for vascular lesions. In the detection of erosive/ulcerative lesions, FICE setting 2 was significantly superior to WL. In tumor images, there was no significant improvement with any of the settings relative to WL images. CONCLUSIONS: FICE is most useful for improving CE image quality and detection in cases of angioectasia and erosion/ulceration of the small intestine. PMID- 26135266 TI - Why should we systematically specify the clinical relevance of images observed at capsule endoscopy? PMID- 26135267 TI - Urgent double balloon endoscopy provides higher yields than non-urgent double balloon endoscopy in overt obscure gastrointestinal bleeding. AB - BACKGROUND AND STUDY AIMS: In overt obscure gastrointestinal bleeding (OV), double balloon endoscopy (DBE) is recommended as one of the most important investigations as it can provide both diagnosis and treatment. However, there is no set standard on the timing of DBE in OV. The aim of this study was to compare the diagnostic and therapeutic yields between urgent and non-urgent DBE in patients with OV. PATIENTS AND METHODS: Between January 2006 and February 2013, 120 patients with OV who underwent DBE were retrospectively reviewed. An urgent DBE was defined as DBE performed within 72 h from the last visible gastrointestinal bleeding (n = 74) whereas a non-urgent DBE was defined as DBE performed after 72 h (n = 46). Diagnostic yields, therapeutic impact and clinical outcomes were evaluated. RESULTS: Diagnostic yield in urgent DBE was significantly higher than that in non-urgent DBE (70 % versus 30 %; P < 0.05). Urgent DBE offered significantly more therapies including endoscopic, angiographic embolization, and surgery than non-urgent DBE (54 % versus 15 %; P < 0.001). Endoscopic therapy was performed in 43 % of urgent-DBE patients whereas only 13 % of patients in the other group received endoscopic therapy (P < 0.01). In patients with identified bleeding sources, the rebleeding rate was lower in patients who underwent urgent DBE than in those who underwent non-urgent DBE (10 % versus 29 %, NS). CONCLUSIONS: Regarding diagnostic and therapeutic impacts in OV, our retrospective study showed that urgent DBE is better than non-urgent DBE. The recurrent bleeding rate in patients undergoing urgent DBE tended to be lower. PMID- 26135268 TI - Cost-effectiveness of colorectal cancer screening in Germany: current endoscopic and fecal testing strategies versus plasma methylated Septin 9 DNA. AB - BACKGROUND AND STUDY AIMS: Colorectal cancer (CRC) screening strategies in Germany include guaiac-based fecal occult blood testing (gFOBT) starting at age 50 and a switch to colonoscopy at age 55 or continued gFOBT testing, but screening utilization is limited. Blood-based biomarkers, such as methylated Septin 9 DNA ( (m) SEPT9), may improve screening rates. We performed a cost effectiveness analysis of current and emerging CRC screening strategies in Germany. METHODS: Using a validated Markov model, we compared annual gFOBT for ages 50 through 54 followed by biennial testing until age 75 (FOBT) or by colonoscopy at ages 55 and 65 (FOBT/COLO 55,65), substitution of fecal immunochemical testing (FIT) for gFOBT (FIT, FIT/COLO 55,65), and annual or biennial plasma (m) SEPT9 testing. We also considered persons who utilize only colonoscopy and varied age at colonoscopy utilization. RESULTS: The current strategies were more effective and less costly than no screening. FIT was more effective and less costly than (m) SEPT9 testing. FIT/COLO 55,65 cost ?12 200 per quality-adjusted life-years gained in comparison with FIT. (m) SEPT9-based screening was cost-effective in comparison with no screening but was dominated by other cost-saving strategies. Differential screening utilization and adherence greatly affected incremental results between strategies. In probabilistic analyses, FIT was preferred in 49 % and FIT/COLO 55,65 in 47 % of iterations. CONCLUSION: Currently available CRC screening strategies in Germany, including hybrid fecal testing/colonoscopy, are likely to be cost-saving. Current strategies appear superior to (m) SEPT9-based screening. The impact of blood based biomarkers is likely to depend on utilization and adherence as much as on test performance characteristics and cost. PMID- 26135270 TI - Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging. AB - Beating in vivo-like human cardiac bodies (CBs) were used in a microfluidic device for testing cardiotoxicity. The CBs, cardiomyocyte cell clusters derived from induced pluripotent stem cells, exhibited typical structural and functional properties of the native human myocardium. The CBs were captured in niches along a perfusion channel in the device. Video imaging was utilized for automatic monitoring of the beating frequency of each individual CB. The device allowed assessment of cardiotoxic effects of drug substances doxorubicin, verapamil and quinidine on the 3D clustered cardiomyocytes. Beating frequency data recorded over a period of 6 hours are presented and compared to literature data. The results indicate that this microfluidic setup with imaging of CB characteristics provides a new opportunity for label-free, non-invasive investigation of toxic effects in a 3D microenvironment. PMID- 26135269 TI - Presence and function of microRNA-92a in chondrogenic ATDC5 and adipose-derived mesenchymal stem cells. AB - The aim of the present study was to investigate the presence and biological function of microRNA-92a (miR-92a) in chondrogenesis and cartilage degeneration. Human adipose-derived mesenchymal stem cells (hADSCs) in micromass and chondrocyte-like ATDC5 cells were induced to chondrogenesis, and primary human/mouse chondrocytes (PHCs/PMCs) and chondrogenic ATDC5 cells were stimulated with interleukin-1beta (IL-1beta). An miR-92a mimic/inhibitor was transfected into the ATDC5 cells using lipofectamine 2000. Gene expression was analyzed using reverse transcription-quantitative polymerase chain reaction. Alcian blue was used to stain the cartilage nodules and chondrogenic micromass. The potential target genes, signaling pathways and functions of miR-92a were examined using miRanda, miRDB, CLIP-Seq, TargetScan and Kyoto Encyclopedia of Genes and Genomes. The expression of miR-92a was elevated in the chondrogenic ATDC5 cells and hADSCs, and also in the IL-1beta-induced ATDC5 cells, PMCs and PHCs. Forced expression of miR-92a enhanced the expression levels of col9a2 and aggrecan. A total of 279 genes were predicted as potential target genes of miR-92a. The phosphoinositide 3-kinase/PI3K)-Akt, ErbB and focal adhesion kinase pathways, extracellular matrix (ECM)-receptor interaction and the mammalian target of rapamycin (mTOR) signaling pathway were suggested to mediate the effects of miR 92a on chondrogenesis and cartilage degeneration. These results demonstrated that miR-92a was involved in chondrogenesis and the chondrocyte response induced by IL 1beta. miR-92a positively contributed to the expression of col9a2 and of aggrecan. PMID- 26135271 TI - Prevalence and risk factors of deep vein thrombosis in patients after spine surgery: a retrospective case-cohort study. AB - Deep vein thrombosis (DVT) is common seen in patients undergoing spine surgery. However, its prevalence and associated risk factors have not been well understood yet. This retrospective case-cohort study was designed to investigate risk factors for postoperative DVT using retrospectively collected data from department of spine surgery between 07/2013 and 07/2014. Univariate analysis and binary logistic regression analysis were used to determine risk factors for DVT. A total of 861 patients were admitted into DVT-associated analyses, including 410 males and 451 females, aged from 15 to 87 years old (median 54, IQR 18). Of them, 147 cases (17%) sustained postoperative DVT. DVT incidence was 15.9% in patients undergoing lumbar interbody fusion, 13.5% in patients treated by low-molecular weight heparin (LMWH), while only 8.1% in patients without LMWH. However, it revealed no significant difference between LMWH group and non-LMWH group (chi(2) = 1.933, p = 0.164). Logistic regression equation was logit P = -4.09 + 0.05*X1 - 0.55*X2 + 0.41*X3 + 1.41*X7, (X1 = age; X2 = regions; X3 = hypertension; X7 = D dimer). In this study, LMWH prophylaxis after spine surgery proved ineffective. Advanced age, D-dimer and hypertension have proved to be the risk factors for postoperative DVT in patients undergoing spine surgery. PMID- 26135272 TI - [Editorial]. PMID- 26135273 TI - [Development and Process Evaluation of the e-Mental Health Portal www.psychenet.de for the Hamburg Network for Mental Health]. AB - OBJECTIVE: The purpose of this project was to develop a user-centered web-portal for empowerment in mental disorders. METHODS: The development of the portal included mixed-methods techniques for needs assessment to identify user-relevant content. Exposure and use of the portal was investigated as part of a process evaluation. RESULTS: psychenet.de informs about mental disorders and treatment option. Results of the process evaluation showed a highly accessed website, the portal was assessed as "good" or "very good" by 73 % of the respondents. DISCUSSION: Using psychenet.de attempts to raise awareness, to inform about mental disorders, and to engage patients in the course of their treatment. PMID- 26135274 TI - [What does the Public Know and Think About Mental Disorders?]. AB - Public knowledge about and attitudes towards mental illness were analyzed. Furthermore, changes in knowledge and attitudes after an information and awareness campaign were examined. The basis were two telephone surveys in 2011 (t0) and 2014 (t1) in Hamburg (intervention) and Munich (control). In 2011, the public was relatively well informed about mental disorders. Regarding the level of information of the public before the campaign and inconsistent results of previous evaluation studies the anticipated impact of the awareness campaign at t1 are moderate. PMID- 26135275 TI - [Peer Support for Individuals with Mental Health Problems and their Relatives - Background, Concept and Baseline Data]. AB - Severe mental illness comes along with cyclic hospital re-admission, heavy losses in quality of life and stigmatization. Therefore a refinement of intervention is still required, for patients themselves and their relatives. In mental health services there is an international trend toward recovery-orientated interventions, like peer support. In Germany this is the first trial to implement peer-support area-wide in a metropolis. This article describes the implementation of the network, the methodology of the research setting and the baseline data of the randomized controlled trial. PMID- 26135276 TI - [Prevention and Treatment of Eating Disorders: The Health Care Network Anorexia and Bulimia nervosa]. AB - The "Health care network anorexia and bulimia nervosa", a subproject of psychenet - the Hamburg network for mental health - aims to decrease the incidence of eating disorders as well as the risk for chronic illness courses. One focal project, therefore, evaluates a school-based prevention manual in a randomized controlled trial. The other one examines the impact of a systemic public health intervention on early treatment initiation in anorexia nervosa. The present article provides an overview about study design and interventions in both focal projects as well as preliminary results. PMID- 26135277 TI - [Sustainable Transfer of the Health Network Alcohol Use in Adolescence: A Cooperation of Research, Practice and Politics]. AB - OBJECTIVES: Testing the effectiveness of a brief motivational intervention in an emergency-setting for adolescents with acute alcohol intoxication in a randomized controlled trial and sustained implementation within mental health care of Hamburg. METHODS: Modification and evaluation of an established indicated prevention program in a transdisciplinary cooperation using a pragmatic RCT research design. CONCLUSIONS: This study contributes to the evidence base of an established prevention program which allows for broad dissemination building on existing capacities for broad dissemination. PMID- 26135278 TI - [Prevention of Mental Health as Part of a Holistic Health Management]. AB - Mental illnesses are increasingly common in workplace environments. But interventions that focus exclusively on reducing workplace-stressors are not enough. It takes long-term primary and secondary preventive, integrated solutions on an individual, role-based and organizational level. The promotion of resources of mental and physical health in everyday work can improve an efficient health development and thus should be fostered systematically. TPIII under psychenet starts at this need and systematically investigates two interventions (Employee Assistance Program, Blended Learning), that are intended to promote personal and job-related resources.This study contributes to the evidence base of an established prevention program which allows for broad dissemination building on existing capacities for broad dissemination. PMID- 26135279 TI - [psychenet - The Hamburg Network for Mental Health]. AB - With the research and development project psychenet: the Hamburg Network for Mental Health (2011 - 2015), the Federal Ministry of Education and Research contributes to strengthening healthcare regions in Germany by establishing new transsectoral cooperations and implementing evaluated innovations. More than 300 partners from research, health care, health industry and government in the Free and Hanseatic City of Hamburg are promoting innovative measures to improve the detection, diagnosis, and treatment for mental disorders. The main objective is to implement integrated healthcare networks based on evidence for effective treatment methods, deriving from high-quality research throughout five indications such as psychosis, depression, somatoform and functional syndromes, anorexia and bulimia and addiction illnesses in adolescence. Those networks are accompanied by additional measures, for example, for improving awareness, information and education for mental health, addressing occupational health or strengthening the participation of patients and their families suffering from mental illness. PMID- 26135280 TI - [Promoting Self-Management in Primary Care - the Association of Motivation for Change, Self-Efficacy and Psychological Distress Prior to the Onset of Intervention]. AB - Anxiety, depressive and somatoform disorders are highly prevalent in primary care. Managing these disorders is time-consuming and requires strong commitment on behalf of the general practitioners (GPs). Furthermore, the resources for the management of these patients are limited by the increasing workload in primary care practices, especially in the German health care system. In order to address the SMADS-study within psychenet - the Hamburg Network for Mental Health (NCT01726387) implements and evaluates a complex, low-threshold, nurse-led intervention using a goal-oriented set of case management and counseling techniques to promote self-management in these patients. This paper investigates the association of the patients' motivation for change and their perceived self efficacy, the primary outcome - to get to know whether the intervention will target the appropriate population. PMID- 26135281 TI - [Early Detection and Integrated Care in Adolescents and Young Adults with Severe Psychotic Illnesses]. AB - This is a prospective 1-year follow-up study comparing a combined intervention consisting of multidimensional early detection strategies with age- and interdisciplinary integrated care (intervention group, n = 120) with standard care (historical control group, n = 105) in adolescents and young adults within the early phase of psychosis. Data at study entry indicate a high complexity and severity of illness. Primary outcome is the 6-month rate of combined symptomatic and functional remission at study endpoint. PMID- 26135282 TI - [psychenet - The Hamburg Network for Mental Health: Evaluation of the Health Network Depression from the Perspective of Participating General Practitioners, Psychotherapists and Psychiatrists]. AB - OBJECTIVE: Evaluation of satisfaction and acceptance of a stepped care model in the Health Network Depression from the perspective of general practitioners, psychotherapists and psychiatrists. METHODS: Cross-sectional questionnaire study with n = 61 care providers. RESULTS: All elements of the stepped care model, e. g. screening, diagnostic, and monitoring checklists, guidelines, low-intensity treatment options and IT-tools were utilized by over 75 % of partners and obtained largely positive ratings. CONCLUSION: This positive evaluation provides a basis for further participative development and transfer into health care. PMID- 26135283 TI - [Improving Health Care for Patients with Somatoform and Functional Disorders: A Collaborative Stepped Care Network (Sofu-Net)]. AB - The management of somatoform disorders in primary care is often limited due to low diagnostic accuracy, delayed referral to psychotherapy and overuse of health care. To address these difficulties, this study aimed to establish a collaborative stepped health care network (Sofu-Net). Sofu-Net was established among 41 primary care physicians, 35 psychotherapists and 8 mental health clinics. Baseline assessment in primary care showed elevated psychopathology and deficits in health care among patients with somatoform symptoms. Network partners provided positive evaluations of Sofu-Net. PMID- 26135284 TI - [psychenet - Hamburg Network for Mental Health: Results of the Process Evaluation]. AB - Aspects of implementation, functionality, acceptability and sustainability of the network psychenet - Hamburg network for mental health were examined.In March 2012 and September 2013, 19 expert interviews were carried out with leaders of subprojects and representatives of insurances, public authorities and patients.The complexity of the network was hindering. Positive aspects were communication, clear hierarchies and qualified staff.The implementation of a complex network requires shared goals. The establishment of a steering committee has proved as crucial. PMID- 26135285 TI - [Health Economic Evaluations within the Hamburg Network for Mental Health]. AB - Within the Hamburg Network for Mental Health, cost-effectiveness analyses of collaborative care models are conducted. After providing an overview of the international literature on the cost-effectiveness of collaborative care for mental disorders, this article describes the rationale, aims and methods of the cost-effectiveness analyses conducted within the Hamburg Network for Mental Health. Proof of cost-effectiveness is expected to promote the transfer of collaborative care models into routine care. PMID- 26135286 TI - [Transfer of Care Innovations from the Hamburg Network for Mental Health to other Health Regions]. AB - The goal of this paper is to present the research conducted for systemizing network elements and analyzing their interconnection that emerged during the establishment and functioning of health care innovation project of psychenet - the Hamburg Network for Mental Health.Semi-structured manual-based face-to-face interviews with project researchers and leaders were conducted. The gathered data was validated and updated several times during the project duration. The results include a systematic description of 186 network elements developed during the overall project and respective subprojects. The elements were consolidated in a web-based database and integrated into the psychenet.de public website. A clustering of elements was conducted and modules of elements were generated based on the interconnection between the related elements.The systematic description of network elements as well as determination of their interconnection and dependency can play an important role in understanding the emergence and functioning of integrated mental health networks. The innovative medical networks prove to be complex service systems and urge for a grounded application of integration techniques in order to be successfully transferred and adopted in other regions. PMID- 26135287 TI - [Transfer and Implementation of Innovative Awareness and Education Measures, e Mental Health and Care Models in psychenet - Hamburg Network for Mental Health]. AB - The Hamburg Network for Mental Health belongs to the healthcare regions in Germany, funded by the Federal Ministry of Education and Research from 2011 to 2015. More than 330 partners from research, health care, health industry and government are promoting innovative health care models and products to improve mental health care in Hamburg. The main objectives comprise the sustained implementation of the Network itself and of successful health care models and products. The article describes current and future implementation possibilities and the present state of the implementation process. PMID- 26135288 TI - [We thank network partners in psychenet for their engagement ]. PMID- 26135289 TI - [Improving Mental Health Literacy and Mental Illness Stigma in the Population of Hamburg]. AB - Evidence shows that poor mental health literacy and stigmatization have negative consequences on mental health. However, studies on interventions to improve both are often heterogenic in methodology and results. The psychenet-campaign in Hamburg was developed and implemented in collaboration with patients and relatives and comprised multidimensional interventions focusing on education and contact to patients. The main goals were the improvement of mental health literacy and destigmatization and the long-term implementation within Hamburg's mental health care system. PMID- 26135291 TI - An HASApf-redoxin complex causing asymmetric catalytic oxidation via the regenerative formation of a reactive oxygen species. AB - A PP (pea)-HASApf-redoxin complex eluted from encapsulated PP gel with aeration displays asymmetric oxidation activity over 200 times greater than that of a similar protein expressed by E. coli cells. The intermediate spin, identified in the ESR spectrum, appears at g = 4.3 and g = 2.0, suggesting that an iron electron-transfer system for the asymmetric oxidation of secondary alcohols may be successfully created by the PP-HASApf-redoxin complex (39 kDa). FTIR experiments provided values nus(SO2) ~ 950-1050 cm(-1) and nuas(SO2) ~ 1100-1200 cm(-1) for metal-bound sulfinate S-O and Fe-O vibrations. The sulfur and iron detected by physicochemical inspection (IC/ICP-AES) may facilitate the electron transport of a sulfate-iron complex (e.g., rubredoxin (6 kDa) or ferredoxin (9 kDa)) to the HASApf (21 kDa). The observations are consistently acceptable; i.e., the oxygen-driven PP-HASApf-redoxin complex functions regenerate via the successive asymmetric catalytic event - Fe(ii) + O2 -> Fe(iii)-O-O(-) -> Fe(iv) = O (oxidizing rac- or rac-) -> Fe(ii) + H2O. Therefore, the use of a raw biomaterial as a PP-HASApf-redoxin complex-catalytic system for asymmetric oxidation is an important novelty, despite the apparent difficulties in working with pure dehydrogenase enzymatic/redox-cofactor systems for biotransformation. PMID- 26135290 TI - Intergenerational epigenetic inheritance in models of developmental programming of adult disease. AB - It is now well established that the environment to which we are exposed during fetal and neonatal life can have a long-term impact on our health. This has been termed the developmental origins of health and disease. Factors known to have such programming effects include intrauterine nutrient availability (determined by maternal nutrition and placental function), endocrine disruptors, toxins and infectious agents. Epigenetic processes have emerged as a key mechanism by which the early environment can permanently influence cell function and metabolism after multiple rounds of cell division. More recently it has been suggested that programmed effects can be observed beyond the first generation and that therefore epigenetic mechanisms could form the basis of transmission of phenotype from parent to child to grandchild and beyond. Here we review the evidence for such processes. PMID- 26135293 TI - A Message from the Editor-in-Chief. PMID- 26135292 TI - Enhancing patient experience through personalization of health services. AB - Patient engagement is a challenge many leaders are facing, as consumer expectations of health services demand a more personalized approach to care. This article examines consumer trends that are influencing patient engagement and empowerment relative to the use of digital technologies. Informed by consumer and population health trends that can personalize health services, three strategies leaders can engage to strengthen patient experience include placing greater focus on personal health and wellness, shifting towards personalized rather than standardized healthcare, and facilitating the democratization of healthcare information. PMID- 26135294 TI - Code orange: Towards transformational leadership of emergency management systems. AB - The 21(st) century calls upon health leaders to recognize and respond to emerging threats and systemic emergency management challenges through transformative processes inherent in the LEADS in a caring environment framework. Using a grounded theory approach, this qualitative study explores key informant perspectives of leaders in emergency management across Canada on pressing needs for relevant systemic transformation. The emerging model points to eight specific attributes of transformational leadership central to emergency management and suggests that contextualization of health leadership is of particular import. PMID- 26135295 TI - The impact and influence of hope and hype in decision-making about health technologies. AB - Decision-making about health technologies is complex. An aspect that is not often addressed is the potential impact of both hope and hype regarding these technologies. This article discusses the commercialization of hope and how "hope hype" can influence our decision-making. As health leaders have a pivotal role in how these types of decisions are made, opportunities for and suggestions related to structuring decision-making processes to critically engage with "hope hype" are also canvassed. PMID- 26135296 TI - Making research integral to home care services. AB - Home care is the fastest growing segment of the Canadian healthcare system, yet research on patient safety has been conducted predominantly in institutional settings. This is a case example of how Victorian Order of Nurses Canada, a national not-for-profit home and community care provider, embedded a nurse researcher to create an environment in which health services research flourished. This model strategically propelled important issues such as home care safety on to the national research and policy agendas and helped leverage change in multiple levels of the healthcare system. This is a call to action for building partnerships to have a researcher as an integral team member in organizations providing home care services. PMID- 26135297 TI - Triage in times of drug shortage. AB - This paper addresses the current drug shortage, and examines the ethics framework for dealing with drug shortages developed by our organization. That three-step allocation process and framework was published previously in this journal. Specifically, this paper offers a rationale and justification for the framework's second step, which involves a triage process aimed to ensure that the available drug supply is utilized effectively and ethically. PMID- 26135299 TI - Abundance and Distribution Characteristics of Microplastics in Surface Seawaters of the Incheon/Kyeonggi Coastal Region. AB - Microplastics in marine environments are of emerging concern due to their widespread distribution, their ingestion by various marine organisms, and their roles as a source and transfer vector of toxic chemicals. However, our understanding of their abundance and distribution characteristics in surface seawater (SSW) remains limited. We investigated microplastics in the surface microlayer (SML) and the SSW at 12 stations near-shore and offshore of the Korean west coast, Incheon/Kyeonggi region. Variation between stations, sampling media, and sampling methods were compared based on abundances, size distribution, and composition profiles of microsized synthetic polymer particles. The abundance of microplastics was greater in the SML (152,688 +/- 92,384 particles/m(3)) than in SSW and showed a significant difference based on the sampling method for SSWs collected using a hand net (1602 +/- 1274 particles/m(3)) and a zooplankton trawl net (0.19 +/- 0.14 particles/m(3)). Ship paint particles (mostly alkyd resin polymer) accounted for the majority of microplastics detected in both SML and SSWs, and increased levels were observed around the voyage routes of large vessels. This indicates that polymers with marine-based origins become an important contributor to microplastics in coastal SSWs of this coastal region. PMID- 26135298 TI - Prosthesis design and placement in reverse total shoulder arthroplasty. AB - The management of irreparable rotator cuff tears associated with osteoarthritis of the glenohumeral joint has long been challenging. Reverse total shoulder arthroplasty (RSA) was designed to provide pain relief and improve shoulder function in patients with severe rotator cuff tear arthropathy. While this procedure has been known to reduce pain, improve strength and increase range of motion in shoulder elevation, scapular notching, rotation deficiency, early implant loosening and dislocation have attributed to complication rates as high as 62%. Patient selection, surgical approach and post-operative management are factors vital to successful outcome of RSA, with implant design and component positioning having a significant influence on the ability of the shoulder muscles to elevate, axially rotate and stabilise the humerus. Clinical and biomechanical studies have revealed that component design and placement affects the location of the joint centre of rotation and therefore the force-generating capacity of the muscles and overall joint mobility and stability. Furthermore, surgical technique has also been shown to have an important influence on clinical outcome of RSA, as it can affect intra-operative joint exposure as well as post-operative muscle function. This review discusses the behaviour of the shoulder after RSA and the influence of implant design, component positioning and surgical technique on post operative joint function and clinical outcome. PMID- 26135300 TI - Effect of Chlorpyrifos Ethyl on Acetylcholinesterase Activity in Climbing Perch (Anabas testudineus, Bloch, 1972). AB - The high use of pesticides in intensive rice farming in the Mekong Delta constitutes a potential hazard to the environment and to people's health. Chlorpyrifos ethyl (CPF) is a commonly used organophosphate (OP) insecticide, but information about its potential negative impacts on the aquatic environment in the Mekong Delta is scarce. Both acute and subacute toxicity tests were performed in a static nonrenewable system to investigate the effects of CPF on brain acetylcholinesterase (AChE) activity in native climbing perch fingerlings (Anabas testudineus, Bloch, 1972). Environmental parameters, such as dissolved oxygen, water temperature, and pH, were similar to field conditions in the Mekong Delta. In a 96-h lethal concentration (LC50) test, fingerlings of climbing perch were randomly exposed to five levels of CPF ranging from 0.8 to 4.5 ppm. Five sublethal levels of CPF (1, 5, 10, 15, and 20 % of the 96-h LC50 value) were tested to assess the sensitivity and recovery of the brain AChE activity in climbing perch fingerlings exposed to CPF. The results showed that CPF were moderately toxic to climbing perch with a 96-h median LC50 of 1.73 ppm. CPF also caused long-term AChE inhibition with 70 % inhibition remaining after 96 h for the four highest test concentrations. The recovery of brain AChE activity in fish placed in CPF-free water was very slow, and after 7 days the brain AChE activity was still significant lower in fish from the four highest concentrations compared with the control. The results from this study indicate that OP insecticides, such as CPF, can have long-lasting sublethal effects on aquatic species in the Mekong Delta. PMID- 26135301 TI - Pesticide Uptake Across the Amphibian Dermis Through Soil and Overspray Exposures. AB - For terrestrial amphibians, accumulation of pesticides through dermal contact is a primary route of exposure in agricultural landscapes and may be contributing to widespread amphibian declines. To show pesticide transfer across the amphibian dermis at permitted label application rates, our study was designed to measure pesticide body burdens after two simulated exposure scenarios. We compared direct exposures, where amphibians were present when spraying occurred, to indirect exposures, where amphibians were exposed to soils after pesticide application. During summer 2012, we reared barking (Hyla gratiosa) and green treefrogs (H. cinerea) through 60-90 days post-metamorphosis at a United States Environmental Protection Agency research laboratory. We tested exposure for 8 h to five pesticide active ingredients (imidacloprid, atrazine, triadimefon, fipronil, or pendimethalin) in glass aquaria lined with soil in the laboratory. We quantified total pesticide body burden and soil concentrations using liquid chromatography mass spectrometry. All individuals in both treatments had measurable body burdens at the end of the study. A randomized block design analysis of variance (n = 18) showed that body burdens (p = 0.03) and bioconcentration factors (BCFs) (p = 0.01) were significantly greater in the direct overspray treatment relative to the indirect soil spray treatment for both species and tested pesticides. BCFs ranged from 0.1 to 1.16 and from 0.013 to 0.78 in the direct and indirect treatments, respectively. Our study shows dermal uptake for multiple pesticides from both direct spray and indirect soil exposures and provides empirical support for the degree to which terrestrial phase amphibians have higher body burdens after overspray pesticide exposure. PMID- 26135303 TI - Correction: Androgen Receptor (AR), E-Cadherin, and Ki-67 as Emerging Targets and Novel Prognostic Markers in Triple-Negative Breast Cancer (TNBC) Patients. PMID- 26135302 TI - Understanding the modifiable health systems barriers to hypertension management in Malaysia: a multi-method health systems appraisal approach. AB - BACKGROUND: The growing burden of non-communicable diseases in middle-income countries demands models of care that are appropriate to local contexts and acceptable to patients in order to be effective. We describe a multi-method health system appraisal to inform the design of an intervention that will be used in a cluster randomized controlled trial to improve hypertension control in Malaysia. METHODS: A health systems appraisal was undertaken in the capital, Kuala Lumpur, and poorer-resourced rural sites in Peninsular Malaysia and Sabah. Building on two systematic reviews of barriers to hypertension control, a conceptual framework was developed that guided analysis of survey data, documentary review and semi-structured interviews with key informants, health professionals and patients. The analysis followed the patients as they move through the health system, exploring the main modifiable system-level barriers to effective hypertension management, and seeking to explain obstacles to improved access and health outcomes. RESULTS: The study highlighted the need for the proposed intervention to take account of how Malaysian patients seek treatment in both the public and private sectors, and from western and various traditional practitioners, with many patients choosing to seek care across different services. Patients typically choose private care if they can afford to, while others attend heavily subsidised public clinics. Public hypertension clinics are often overwhelmed by numbers of patients attending, so health workers have little time to engage effectively with patients. Treatment adherence is poor, with a widespread belief, stemming from concepts of traditional medicine, that hypertension is a transient disturbance rather than a permanent asymptomatic condition. Drug supplies can be erratic in rural areas. Hypertension awareness and education material are limited, and what exist are poorly developed and ineffective. CONCLUSION: Despite having a relatively well funded health system offering good access to care, Malaysia's health system still has significant barriers to effective hypertension management. DISCUSSION: The study uncovered major patient-related barriers to the detection and control of hypertension which will have an impact on the design and implementation of any hypertension intervention. Appropriate models of care must take account of the patient modifiable health systems barriers if they are to have any realistic chance of success; these findings are relevant to many countries seeking to effectively control hypertension despite resource constraints. PMID- 26135304 TI - Correction: Dielectrical Properties of CeO2 Nanoparticles at Different Temperatures. PMID- 26135305 TI - Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat. AB - Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise. Using the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia-induced hypertension in the rat, we determined the effect of neutrophil depletion on blood pressure and fetal resorptions. Neutrophils were depleted with repeated injections of polyclonal rabbit anti-rat polymorphonuclear leukocyte (PMN) antibody (antiPMN). Rats received either antiPMN or normal rabbit serum (Control) on 13.5, 15.5, 17.5, and 18.5 days post conception (dpc). On 14.5 dpc, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP). On 18.5 dpc, carotid arterial catheters were placed and mean arterial pressure (MAP) was measured on 19.5 dpc. Neutrophil-depleted rats had reduced circulating neutrophils from 14.5 to 19.5 dpc compared to Control, as well as decreased neutrophils in lung and placenta on 19.5 dpc. MAP increased in RUPP Control vs Sham Control rats, and neutrophil depletion attenuated this increase in MAP in RUPP rats without any effect on Sham rats. The RUPP-induced increase in fetal resorptions and complement activation product C3a were not affected by neutrophil depletion. Thus, these data are the first to indicate that neutrophils play an important role in RUPP hypertension and that cells of the innate immune system may significantly contribute to pregnancy-induced hypertension. PMID- 26135306 TI - Validation of major prognostic models for metastatic urothelial carcinoma using a multi-institutional cohort of the real world. AB - BACKGROUND: Several prognostic models predicting survival of patients with metastatic urothelial carcinoma (UC) have been developed; however, of them, the first model by Bajorin in 1999 is still the most representative and widely used, and validations of newer models are lacking. This study aimed to validate three major prognostic models for metastatic UC constructed based on clinical trials. METHODS: We reviewed 200 patients with metastatic UC who received first-line chemotherapy at our five affiliate institutions between 2003 and 2011. Using this multi-institutional cohort, we validated the following models: the "Bajorin model," a model consisting of visceral metastasis and performance status; the "Apolo model," a nomogram including visceral metastasis, performance status, albumin and hemoglobin; and the "Galsky model," a nomogram including leukocyte count, number of sites of visceral metastases, site of primary tumor, performance status and lymph node metastasis. Harrell's c-index was calculated for each model. Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Among 200 patients, 171 (85.5%) died during the follow-up, with a median survival of 12.0 months. Multivariate analysis demonstrated ECOG performance status, visceral metastasis and leukocyte count to be independent predictors of overall survival. C-index results (95% confidence interval) were Bajorin: 0.86 (0.74-0.95); Apolo: 0.89 (0.78-0.98); and Galsky: 0.82 (0.69-0.93). CONCLUSIONS: All models were demonstrated to have high external validities in real-world patients, and of them, the "Apolo model" achieved the highest c-index in the present population. Further studies with larger populations are needed for establishment of the next standard model. PMID- 26135307 TI - The morbidity of laparoscopic radical cystectomy: analysis of postoperative complications in a multicenter cohort by the European Association of Urology (EAU)-Section of Uro-Technology. AB - PURPOSE: To analyze postoperative complications after laparoscopic radical cystectomy (LRC) and evaluate its risk factors in a large prospective cohort built by the ESUT across European centers involved in minimally invasive urology in the last decade. METHODS: Patients were prospectively enrolled, and data were retrospectively analyzed. Only oncologic cases were included. There were no formal contraindications for LRC: Also patients with locally advanced tumors (pT4a), serious comorbidities, and previous major abdominal surgery were enrolled. All procedures were performed via a standard laparoscopic approach, with no robotic assistance. Early and late postoperative complications were graded according to the modified Clavien-Dindo classification. Multivariate logistic regression was performed to explore possible risk factors for developing complications. RESULTS: A total of 548 patients were available for final analysis, of which 258 (47%) experienced early complications during the first 90 days after LRC. Infectious, gastrointestinal, and genitourinary were, respectively, the most frequent systems involved. Postoperative ileus occurred in 51/548 (9.3%) patients. A total of 65/548 (12%) patients underwent surgical re operation, and 10/548 (2%) patients died in the early postoperative period. Increased BMI (p = 0.024), blood loss (p = 0.021), and neoadjuvant treatment (p = 0.016) were significantly associated with a greater overall risk of experiencing complications on multivariate logistic regression. Long-term complications were documented in 64/548 (12%), and involved mainly stenosis of the uretero-ileal anastomosis or incisional hernias. CONCLUSIONS: In this multicenter, prospective, large database, LRC appears to be a safe but morbid procedure. Standardized complication reporting should be encouraged to evaluate objectively a surgical procedure and permit comparison across studies. PMID- 26135308 TI - Spatial Patterns and Temperature Predictions of Tuna Fatty Acids: Tracing Essential Nutrients and Changes in Primary Producers. AB - Fatty acids are among the least understood nutrients in marine environments, despite their profile as key energy components of food webs and that they are essential to all life forms. Presented here is a novel approach to predict the spatial-temporal distributions of fatty acids in marine resources using generalized additive mixed models. Fatty acid tracers (FAT) of key primary producers, nutritional condition indices and concentrations of two essential long chain (>=C20) omega-3 fatty acids (EFA) measured in muscle of albacore tuna, Thunnus alalunga, sampled in the south-west Pacific Ocean were response variables. Predictive variables were: location, time, sea surface temperature (SST) and chlorophyll-a (Chla), and phytoplankton biomass at time of catch and curved fork length. The best model fit for all fatty acid parameters included fish length and SST. The first oceanographic contour maps of EFA and FAT (FATscapes) were produced and demonstrated clear geographical gradients in the study region. Predicted changes in all fatty acid parameters reflected shifts in the size-structure of dominant primary producers. Model projections show that the supply and availability of EFA are likely to be negatively affected by increases in SST especially in temperate waters where a 12% reduction in both total fatty acid content and EFA proportions are predicted. Such changes will have large implications for the availability of energy and associated health benefits to high-order consumers. Results convey new concerns on impacts of projected climate change on fish-derived EFA in marine systems. PMID- 26135309 TI - Climate-sensitive health priorities in Nunatsiavut, Canada. AB - BACKGROUND: This exploratory study used participatory methods to identify, characterize, and rank climate-sensitive health priorities in Nunatsiavut, Labrador, Canada. METHODS: A mixed method study design was used and involved collecting both qualitative and quantitative data at regional, community, and individual levels. In-depth interviews with regional health representatives were conducted throughout Nunatsiavut (n = 11). In addition, three PhotoVoice workshops were held with Rigolet community members (n = 11), where participants took photos of areas, items, or concepts that expressed how climate change is impacting their health. The workshop groups shared their photographs, discussed the stories and messages behind them, and then grouped photos into re-occurring themes. Two community surveys were administered in Rigolet to capture data on observed climatic and environmental changes in the area, and perceived impacts on health, wellbeing, and lifestyles (n = 187). RESULTS: Climate-sensitive health pathways were described in terms of inter-relationships between environmental and social determinants of Inuit health. The climate-sensitive health priorities for the region included food security, water security, mental health and wellbeing, new hazards and safety concerns, and health services and delivery. CONCLUSIONS: The results highlight several climate-sensitive health priorities that are specific to the Nunatsiavut region, and suggest approaching health research and adaptation planning from an EcoHealth perspective. PMID- 26135310 TI - The Use of Unidirectional Barbed Suture for Urethrovesical Anastomosis during Robot-Assisted Radical Prostatectomy: A Systematic Review and Meta-Analysis of Efficacy and Safety. AB - BACKGROUND: Unidirectional barbed suture (UBS) has been widely used for surgery in recent years, especially for urethrovesical anastomosis (UVA) during robot assisted radical prostatectomy (RARP). However, the efficacy and safety comparing it with conventional non-barbed suture (CS) for UVA is still controversial. AIMS: The objective of this study is to assess the current evidence regarding the efficacy and safety of UBS compared with CS for UVA during RARP. METHODS: We comprehensively searched PubMed, Embase, The Cochrane Library, SinoMed (Chinese) and other databases on Oct. 9, 2014 to conduct a systematic review and meta analysis of all randomized controlled trials (RCTs) and other comparative studies evaluating these two types of suture. The outcome measures included anastomosis time operative time, posterior reconstruction (PR) time, postoperative leakage (PL) rate and continence rates at different time points (4-6 weeks, 3 months, 6 12 months) after surgery. Secondary outcomes included estimated blood loss (EBL) and length of catheterization (LOC). RESULTS: Three RCTs and six observational studies including 786 cases were identified. Meta-analysis of extractable data showed that use of UBS could significantly reduce anastomosis time (weighted mean difference [WMD]:-3.98min; 95% confidence interval [CI], -6.02 -1.95; p = 0.0001), operative time (WMD:-10.06min; 95% CI, -15.45--4.67; p = 0.0003) and PR time (WMD:-0.93min; 95% CI, -1.52--0.34; p = 0.002). No significant difference was found in PL rate, EBL, LOC, or continence rates at 4-6 weeks, 3 months and 6 12 months after surgery. CONCLUSIONS: Our meta-analysis indicates that UBS appears to be safe and efficient as CS for UVA during RARP with not only shorter anastomosis time, operative time, PR time, but also equivalent PL rate, EBL, LOC, and continence rates at 4-6 weeks, 3 months and 6-12 months after surgery. For the inherent limitations of the eligible studies, future more persuasive RCTs are needed to confirm and update our findings. PMID- 26135312 TI - Gene of the month: KIT. AB - Deranged pathway activation and KIT mutations occur in numerous solid and haematological malignancies, with gain-of-function mutations being the most common demonstrable abnormality. Through a complex series of interactions, activation of the KIT receptor tyrosine kinase leads to cell survival, evasion of apoptosis, angiogenesis, dysregulated cell cycle control and promotion of tumourigenesis. The KIT receptor tyrosine kinase is a well-studied therapeutic target in human malignancies. The KIT mutational status of a neoplasm plays an important role in predicting the response to targeted therapies. In this article we outline the structure, function and mutations of the KIT gene, its role in various neoplasms, therapeutic impacts and the role that these play in clinical patient outcome. PMID- 26135313 TI - Subcellular localisation of anillin is associated with different survival outcomes in upper urinary tract urothelial carcinoma. AB - BACKGROUND: The protein anillin (ANLN) has important roles in cell cytokinesis. Until now, no studies have evaluated the role of ANLN expression in a large cohort of patients with urothelial carcinoma of the upper urinary tract (UCUT). METHODS: This study analysed 156 cases of primary localised UCUT. Pathological slides were reviewed and clinical findings were collected. An immunohistochemical study was performed and the cytoplasmic and nuclear staining results of UCUT were recorded. Expressions of ANLN were analysed to identify correlations with various clinicopathological parameters, disease-specific survival (DSS) and metastasis free survival (MeFS). RESULTS: Overexpression of ANLN in the nucleus had significant positive associations with tumour stage (p=0.017), histological grade (p=0.040), mitotic count (p=0.023), tumour necrosis (p=0.009), invasion patterns (p<0.001) and simultaneous involvement of the renal pelvis and ureter (p=0.032). Overexpression of ANLN in the cytoplasm had a significant negative correlation with patient age (p=0.004), tumour grade (p=0.021) and vascular invasion (p=0.013). Notably, univariable analysis showed that overexpression of ANLN in the nucleus was significantly associated with a poor DSS (p=0.006) and MeFS (p=0.010), and multivariable analysis showed that it was an independent predictor of adverse DSS outcome (p=0.031, relative risk 1.535). Low expression of ANLN in the cytoplasm was strongly associated with a poor DSS (p=0.045) and MeFS (p=0.041) in univariable analysis but not in Cox regression analysis. CONCLUSIONS: Subcellular localisation of ANLN is correlated with different tumour phenotypes and probably confers different tumorigenicity. Since high nuclear expression of ANLN is also an independent predictor of poor DSS, it is a useful prognostic marker of UCUT. PMID- 26135314 TI - Clinical use of low haemoglobin density, transferrin saturation, bone marrow morphology, Perl's stain and other plasma markers in the identification of treatable anaemia presenting for cardiac surgery in a prospective cohort study. AB - OBJECTIVES: The differential diagnosis between iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD) with or without associated iron deficiency can be challenging. We assessed the use of different parameters, both classical like ferritin, transferrin saturation and stainable bone marrow iron stores, and novel markers such as low haemoglobin density (LHD) and hepcidin to help discriminate between the three entities. This would allow the detection of patients with ACD with associated iron deficiency, which could benefit from iron supplementation that would have otherwise remained undetected. MATERIALS AND METHODS: Prospective and observational cohort study from 2012 to 2013 where 200 anaemic cardiac surgical patients were recruited and 165 were studied. Detailed blood and bone marrow analyses were performed to establish the aetiology of anaemia. RESULTS: Seventy-four patients (44.8%) had ACD and 29 (39%) of these had an elevated LHD indicating concomitant iron deficiency. Hepcidin was inappropriately normal or increased in the IDA and ACD group. Mean hepcidin was however lower in the group with IDA (4.8 ng/mL) than in the ACD group (15.0 ng/mL; p=0.002). Median hepcidin was lower in patients with ACD and iron restriction as indicated by LHD >4% (17.5 ng/mL) than on those with no iron restriction (25.9 ng/mL; p=0.045). In patients with ACD there was no concordance between Perl's stain and LHD. CONCLUSIONS: LHD was superior to hepcidin and bone marrow iron stores in identifying patients with ACD and associated iron deficiency, which would potentially benefit from parenteral iron therapy. PMID- 26135315 TI - Surgical predictors of acute postoperative pain after hip arthroscopy. AB - BACKGROUND: Pain following hip arthroscopy is highly variable and can be severe. Little published data exists demonstrating reliable predictors of significant pain after hip arthroscopy. The aim of this study was to identify influence of intraoperative factors (arthroscopic fluid infusion pressure, operative type) on the severity of postoperative pain. METHODS: A retrospective review of 131 patients who had received a variety of arthroscopic hip interventions was performed. A standardized anaesthetic technique was used on all patients and postoperative pain was analysed using recovery pain severity outcomes and analgesic use. A multivariate logistic regression analysis was performed on intraoperative factors including patient age, sex and BMI, arthroscopic infusion pressures (40 vs 80 mm Hg), amount of fluid used, length of surgery and types of arthroscopic interventions performed. Thirty six patients were also prospectively examined to determine arthroscopic fluid infusion rates for 40 and 80 mm Hg infusion pressures. RESULTS: Use of a higher infusion pressure of 80 mm Hg was strongly associated with all pain severity endpoints (OR 2.8 - 8.2). Other significant factors included hip arthroscopy that involved femoral chondro ostectomy (OR 5.8) and labral repair (OR 7.5). Length of surgery and total amount of infusion fluid used were not associated with increased pain. CONCLUSIONS: 80 mm Hg arthroscopic infusion pressures, femoral chondro-osteoectomy and labral repair are strongly associated with significant postoperative pain, whereas intraoperative infusion volumes or surgical duration are not. Identification of these predictors in individual patients may guide clinical practice regarding the choice of more invasive regional analgesia options. The use of 40 mm Hg arthroscopic infusion pressures will assist in reducing postoperative pain. PMID- 26135316 TI - Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells. AB - An epidemiological study showed that green tea consumption is associated with a reduced risk of hematopoietic malignancy. The major green tea polyphenol epigallocatechin-3-O-gallate (EGCG) is reported to have anticancer effects. Chronic myeloid leukemia (CML) is a major hematopoietic malignancy characterized by expansion of myeloid cells. In the present study, we showed EGCG-induced acid sphingomyelinase (ASM) activation and lipid raft clustering in CML cells. The ASM inhibitor desipramine significantly reduced EGCG-induced cell death. Protein kinase Cdelta is a well-known kinase that plays an important role in ASM activation. We observed EGCG-induced phosphorylation of protein kinase Cdelta at Ser664. Importantly, EGCG-induced ASM activation was significantly reduced by pretreatment of CML cells with the soluble guanylate cyclase inhibitor NS2028, suggesting that EGCG induced ASM activation through the cyclic guanosine monophosphate (cGMP)-dependent pathway. Indeed, pharmacological inhibition of a cGMP-negative regulator enhanced the anti-CML effect of EGCG. These results indicate that EGCG-induced cell death via the cGMP/ASM pathway in CML cells. PMID- 26135317 TI - Bayesian Spatial NBDA for Diffusion Data with Home-Base Coordinates. AB - Network-based diffusion analysis (NBDA) is a statistical method that allows the researcher to identify and quantify a social influence on the spread of behaviour through a population. Hitherto, NBDA analyses have not directly modelled spatial population structure. Here we present a spatial extension of NBDA, applicable to diffusion data where the spatial locations of individuals in the population, or of their home bases or nest sites, are available. The method is based on the estimation of inter-individual associations (for association matrix construction) from the mean inter-point distances as represented on a spatial point pattern of individuals, nests or home bases. We illustrate the method using a simulated dataset, and show how environmental covariates (such as that obtained from a satellite image, or from direct observations in the study area) can also be included in the analysis. The analysis is conducted in a Bayesian framework, which has the advantage that prior knowledge of the rate at which the individuals acquire a given task can be incorporated into the analysis. This method is especially valuable for studies for which detailed spatially structured data, but no other association data, is available. Technological advances are making the collection of such data in the wild more feasible: for example, bio-logging facilitates the collection of a wide range of variables from animal populations in the wild. We provide an R package, spatialnbda, which is hosted on the Comprehensive R Archive Network (CRAN). This package facilitates the construction of association matrices with the spatial x and y coordinates as the input arguments, and spatial NBDA analyses. PMID- 26135318 TI - Population Pharmacokinetics of an Indian F(ab')2 Snake Antivenom in Patients with Russell's Viper (Daboia russelii) Bites. AB - BACKGROUND: There is limited information on antivenom pharmacokinetics. This study aimed to investigate the pharmacokinetics of an Indian snake antivenom in humans with Russell's viper bites. METHODS/PRINCIPAL FINDINGS: Patient data and serial blood samples were collected from patients with Russell's viper (Daboia russelii) envenoming in Sri Lanka. All patients received Indian F(ab')2 snake antivenom manufactured by VINS Bioproducts Ltd. Antivenom concentrations were measured with sandwich enzyme immunoassays. Timed antivenom concentrations were analysed using MONOLIXvs4.2. One, two and three compartment models with zero order input and first order elimination kinetics were assessed. Models were parameterized with clearance (CL), intercompartmental clearance (Q), central compartment volume (V) and peripheral compartment volume (VP). Between-subject variability (BSV) on relative bioavailability (F) was included to account for dose variations. Covariates effects (age, sex, weight, antivenom batch, pre antivenom concentrations) were explored by visual inspection and in model building. There were 75 patients, median age 57 years (40-70 y) and 64 (85%) were male. 411 antivenom concentration data points were analysed. A two compartment model with zero order input, linear elimination kinetics and a combined error model best described the data. Inclusion of BSV on F and weight as a covariate on V improved the model. Inclusion of pre-antivenom concentrations or different batches on BSV of F did not. Final model parameter estimates were CL,0.078 L h( 1), V,2.2L, Q,0.178 L h(-1) and VP,8.33L. The median half-life of distribution was 4.6 h (10-90%iles:2.6-7.1 h) and half-life of elimination, 140 h (10th-90th percentilesx:95-223h). CONCLUSION: Indian F(ab')2 snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life. PMID- 26135319 TI - Exogenous glycinebetaine alleviates the detrimental effect of Cd stress on perennial ryegrass. AB - Glycinebetaine (GB) is an important organic osmolyte that accumulates in many plant species in response to abiotic stresses including heavy metals. The objective of this study was to investigate whether exogenous GB would ameliorate the adverse effect of cadmium (Cd) stress on perennial ryegrass (Lolium perenne). Fifty-three days old seedlings were exposed to hydroponic culture for 7 days with six treatments: T1 (control), T2 (0 mM Cd + 20 mM GB), T3 (0 mM Cd + 50 mM GB), T4 (0.5 mM Cd + 0 mM GB), T5 (0.5 mM Cd + 20 mM GB), T6 (0.5 mM Cd + 50 mM GB). Cd stress resulted in a remarkable decrease in turf quality, vertical shoot growth rate (VSGR), normalized relative transpiration (NRT) and Chlorophyll (Chl) content; with significant increases in electric conductivity (EL), malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) activity, oxalic and tartaric acid content. Exogenous application of GB decreased EL and MDA content in Cd stressed plants, and increased turf quality, VSGR, NRT, Chl content, SOD, CAT, POD activity, oxalic, tartaric acid content, and the gene expression level of SOD and POD when compared with Cd stressed without GB. Perennial ryegrass with 20 mM GB application suppressed the Cd accumulation in both shoots and roots. A lower translocation factor of Cd was found in GB treated plants than non-GB treated plants, and the lowest translocation factor was observed in the 20 mM GB application. These results suggested that GB could alleviate the detrimental effect of Cd on perennial ryegrass and the amelioration was mainly related to the elevation in SOD, CAT, and POD at enzyme and gene expression levels, which reduced Cd content in shoots and improved cell membrane stability by reducing oxidation of membrane lipids. These findings lead us to conclude that application of GB with 20 mM is the best strategy to ameliorate the detrimental impacts of Cd stress on perennial ryegrass. PMID- 26135320 TI - Complete genome analysis of two new bacteriophages isolated from impetigo strains of Staphylococcus aureus. AB - Exfoliative toxin A (ETA)-coding temperate bacteriophages are leading contributors to the toxic phenotype of impetigo strains of Staphylococcus aureus. Two distinct eta gene-positive bacteriophages isolated from S. aureus strains which recently caused massive outbreaks of pemphigus neonatorum in Czech maternity hospitals were characterized. The phages, designated phiB166 and phiB236, were able to transfer the eta gene into a prophageless S. aureus strain which afterwards converted into an ETA producer. Complete phage genome sequences were determined, and a comparative analysis of five designed genomic regions revealed major variances between them. They differed in the genome size, number of open reading frames, genome architecture, and virion protein patterns. Their high mutual sequence similarity was detected only in the terminal regions of the genome. When compared with the so far described eta phage genomes, noticeable differences were found. Thus, both phages represent two new lineages of as yet not characterized bacteriophages of the Siphoviridae family having impact on pathogenicity of impetigo strains of S. aureus. PMID- 26135323 TI - Intensive ultrasound treatment in acute calcific periarthritis of the wrist: a case report. PMID- 26135321 TI - First mid-term results after cancellous allograft vitalized with autologous bone marrow for infected femoral non-union. AB - BACKGROUND: Surgical treatment of infected femoral non-union is challenging. Only few reports exist including autologous bone grafting (ABG) from the iliac crest promoting union. Vitalized allogeneic bone grafting (VABG) is an alternative promoting osseous healing and reconstructing bone defects. VABG contains allogeneic cancellous bone, impregnated with autologous bone marrow puncture harvested from the iliac crest. Yet, no systematic trial exists summarizing the results of septic femoral non-union using VABG analyzing the infection eradication rate, rate of osseous integration with union, and osseous remodeling. METHODS: In this prospective non-randomized cohort study, 18 patients treated by nailing or plating for femur fractures that subsequently developed a septic non union were included. The surgical intervention included a standardized protocol by eradicating infection first, followed by implantation VABG to promote osseous union. Main outcome measurements were radiographic union and clinical parameters. RESULTS: Mean follow-up was 5.9 years (range: 2-8 years). Infection eradication was achieved for all patients, while union was achieved in 15 out of 18 cases (83.3 %). Mean time for union took 16.9 weeks (range: 12-24). Radiographic analysis proved osseous remodeling and full integration of VABG within 12 months for 15 patients. No infection recurrence occurred at final follow-up. CONCLUSIONS: VABG demonstrated a high union rate without donor site morbidity as the main advantage over ABG. Sufficient osseous integration within 3 months and remodeling within 12 months are promising aspects, as no late fatigue fractures occurred. However, further trials are necessary due to the limitations of this study. PMID- 26135322 TI - A patient with ileocecal Crohn's disease who has intermittent umbilical and left lower abdominal quadrant pain. PMID- 26135325 TI - Effects of Surfactants and Polyelectrolytes on the Interaction between a Negatively Charged Surface and a Hydrophobic Polymer Surface. AB - We have measured and characterized how three classes of surface-active molecules self-assemble at, and modulate the interfacial forces between, a negatively charged mica surface and a hydrophobic end-grafted polydimethylsiloxane (PDMS) polymer surface in solution. We provide a broad overview of how chemical and structural properties of surfactant molecules result in different self-assembled structures at polymer and mineral surfaces, by studying three characteristic surfactants: (1) an anionic aliphatic surfactant, sodium dodecyl sulfate (SDS), (2) a cationic aliphatic surfactant, myristyltrimethylammonium bromide (MTAB), and (3) a silicone polyelectrolyte with a long-chain PDMS midblock and multiple cationic end groups. Through surface forces apparatus measurements, we show that the separate addition of three surfactants can result in interaction energies ranging from fully attractive to fully repulsive. Specifically, SDS adsorbs at the PDMS surface as a monolayer and modifies the monotonic electrostatic repulsion to a mica surface. MTAB adsorbs at both the PDMS (as a monolayer) and the mica surface (as a monolayer or bilayer), resulting in concentration dependent interactions, including a long-range electrostatic repulsion, a short range steric hydration repulsion, and a short-range hydrophobic attraction. The cationic polyelectrolyte adsorbs as a monolayer on the PDMS and causes a long range electrostatic attraction to mica, which can be modulated to a monotonic repulsion upon further addition of SDS. Therefore, through judicious selection of surfactants, we show how to modify the magnitude and sign of the interaction energy at different separation distances between hydrophobic and hydrophilic surfaces, which govern the static and kinetic stability of colloidal dispersions. Additionally, we demonstrate how the charge density of silicone polyelectrolytes modifies both their self-assembly at polymer interfaces and the robust adhesion of thin PDMS films to target surfaces. PMID- 26135326 TI - Mechanistic Details of Pd(II)-Catalyzed C-H Iodination with Molecular I2: Oxidative Addition vs Electrophilic Cleavage. AB - Transition metal-catalyzed C-H bond halogenation is an important alternative to the highly utilized directed-lithiation methods and increases the accessibility of the synthetically valuable aryl halide compounds. However, this approach often requires impractical reagents, such as IOAc, or strong co-oxidants. Therefore, the development of methodology utilizing inexpensive oxidants and catalyst containing earth-abundant transition metals under mild experimental conditions would represent a significant advance in the field. Success in this endeavor requires a full understanding of the mechanisms and reactivity governing principles of this process. Here, we report intimate mechanistic details of the Pd(II)-catalyzed C-H iodination with molecular I2 as the sole oxidant. Namely, we elucidate the impact of the: (a) Pd-directing group (DG) interaction, (b) nature of oxidant, and (c) nature of the functionalized C-H bond [C(sp(2))-H vs C(sp(3)) H] on the Pd(II)/Pd(IV) redox and Pd(II)/Pd(II) redox-neutral mechanisms of this reaction. We find that both monomeric and dimeric Pd(II) species may act as an active catalyst during the reaction, which preferentially proceeds via the Pd(II)/Pd(II) redox-neutral electrophilic cleavage (EC) pathway for all studied substrates with a functionalized C(sp(2))-H bond. In general, a strong Pd-DG interaction increases the EC iodination barrier and reduces the I-I oxidative addition (OA) barrier. However, the increase in Pd-DG interaction alone is not enough to make the mechanistic switch from EC to OA: This occurs only upon changing to substrates with a functionalized C(sp(3))-H bond. We also investigated the impact of the nature of the electrophile on the C(sp(2))-H bond halogenation. We predicted molecular bromine (Br2) to be more effective electrophile for the C(sp(2))-H halogenation than I2. Subsequent experiments on the stoichiometric C(sp(2))-H bromination by Pd(OAc)2 and Br2 confirmed this prediction.The findings of this study advance our ability to design more efficient reactions with inexpensive oxidants under mild experimental conditions. PMID- 26135327 TI - Pooled Nucleic Acid Testing to Detect Antiretroviral Treatment Failure in HIV Infected Patients in Mozambique. AB - BACKGROUND: In resource-limited settings, viral load monitoring of HIV-infected patients receiving antiretroviral therapy (ART) is not readily available because of high costs. Here, we compared the accuracy and costs of quantitative and qualitative pooled methods with standard viral load testing. METHODS: Blood was collected prospectively from 461 patients receiving first-line ART in Mozambique who had not been evaluated previously with viral load testing. Screening for virologic failure of ART was performed quantitatively (ie, standard viral loads) and qualitatively [one and 2 rounds of polymerase chain reaction (PCR)]. Individual samples and minipools of 5 samples were then analyzed using both methods. The relative efficiency, accuracy, and costs of each method were calculated based on viral load thresholds for ART failure. RESULTS: Standard viral load testing of individual samples revealed a high rate of ART failure (19% 23%) across all virologic failure thresholds, and the majority of the patients (93%) with viral loads >1500 copies per milliliter had genotypic resistance to drugs in their ART regimen. Pooled quantitative screening and deconvolution testing had positive and negative predictive values exceeding 95% with cost savings of $11,250 compared with quantitative testing of each sample individually. Pooled qualitative screening and deconvolution testing had a higher cost savings of $30,147 for 1 PCR round and $25,535 for 2 PCR rounds compared with quantitative testing each sample individually. Both pooled qualitative PCR methods had positive and negative predictive values >=90%, but the pooled 1-round PCR method had a sensitivity of 64%. CONCLUSIONS: Given the high rate of undiagnosed ART failure and drug resistance in this cohort, it is clear that virologic monitoring is urgently needed in this population. Here, we compared alternative methods of virologic monitoring with standard viral load testing of individual samples and found these methods to be cost saving and accurate. The test characteristics of each method will likely need to be considered for each local population before it is adopted. PMID- 26135328 TI - Biological reactivity of zinc oxide nanoparticles with mammalian test systems: an overview. AB - Zinc oxide nanoparticles (ZnO NPs) have useful physicochemical advantages, and are used extensively. This has raised concerns regarding their potential toxicity. ZnO NP attributes that contribute to cytotoxicity and immune reactivity, however, seem to vary across literature considerably. Largely, dissolution and generation of reactive oxygen species appear to be the most commonly reported paradigms. Moreover, ZnO NP size and shape may also contribute toward their overall nano-bio interactions. Analysis is further complicated by factors such as adsorption of proteins on the NP surface, which may influence their bioreactivity. The main aim of this review is to give a systematic overview of the postulates explaining cytotoxic, inflammatory and genotoxic effects of ZnO NPs when exposed to different types of cells in vitro and in vivo. PMID- 26135330 TI - Smart Technology in Lung Disease Clinical Trials. AB - This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. PMID- 26135331 TI - Is the Internet gaming-addicted brain close to be in a pathological state? AB - Internet gaming addiction (IGA) is becoming a common and widespread mental health concern. Although IGA induces a variety of negative psychosocial consequences, it is yet ambiguous whether the brain addicted to Internet gaming is considered to be in a pathological state. We investigated IGA-induced abnormalities of the brain specifically from the network perspective and qualitatively assessed whether the Internet gaming-addicted brain is in a state similar to the pathological brain. Topological properties of brain functional networks were examined by applying a graph-theoretical approach to analyzing functional magnetic resonance imaging data acquired during a resting state in 19 IGA adolescents and 20 age-matched healthy controls. We compared functional distance based measures, global and local efficiency of resting state brain functional networks between the two groups to assess how the IGA subjects' brain was topologically altered from the controls' brain. The IGA subjects had severer impulsiveness and their brain functional networks showed higher global efficiency and lower local efficiency relative to the controls. These topological differences suggest that IGA induced brain functional networks to shift toward the random topological architecture, as exhibited in other pathological states. Furthermore, for the IGA subjects, the topological alterations were specifically attributable to interregional connections incident on the frontal region, and the degree of impulsiveness was associated with the topological alterations over the frontolimbic connections. The current findings lend support to the proposition that the Internet gaming-addicted brain could be in the state similar to pathological states in terms of topological characteristics of brain functional networks. PMID- 26135329 TI - Body iron status and gastric cancer risk in the EURGAST study. AB - Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2 = 0.80, 95% CI = 0.72-0.88; OR10%increment = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 ug/dl = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis. PMID- 26135332 TI - Interactive effects of stress and individual differences on alcohol use and posttraumatic stress disorder among personnel deployed to Guantanamo Bay. AB - This study examines the role of factors such as perceived stress, neuroticism, beliefs in psychotherapy stigma, resilience, and demographics in understanding posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) among deployed military personnel. Results show that personnel who screened positive for PTSD were more likely to screen positive for AUD (versus those who did not screen positive for PTSD). Perceived stress, neuroticism, and psychotherapy stigma all have direct multivariate relationships with PTSD symptoms. Moderated regression analyses show that the positive relationship between perceived stress and PTSD symptoms is significantly stronger among those scoring high on neuroticism and psychotherapy stigma. The positive relationship between perceived stress and AUD symptoms is only significant among those scoring high on psychotherapy stigma. Given the moderating role of psychotherapy stigma in the relationship between perceived stress and PTSD symptoms and the relationship between perceived stress and AUD symptoms efforts to reduce the stigma associated with mental health care in the military should be expanded. Also, the current research adds to the literature highlighting the role of neuroticism as a key variable in understanding PTSD. PMID- 26135334 TI - Gender differences in satisfaction ratings for nicotine electronic cigarettes by first-time users. AB - INTRODUCTION: Nicotine electronic cigarettes (NECs) are becoming increasingly popular as a potentially safer alternative to tobacco but little is known regarding their subjective effects, including possible gender differences. METHOD: Participants were New Zealand smokers with no intention to quit (N = 357) and whom had never used an NEC. During an interview in November-December 2012, participants sampled an NEC and rated it and their own-brand tobacco for satisfaction on a 10-point visual analogue scale. Participants were contacted again in February-March 2013 after a 10% increase in the tobacco excise tax on 1 January 2013. RESULTS: Overall participants rated NECs 83.3% as satisfying as own brand tobacco. Females rated NECs more highly than males. Of those who agreed to be re-interviewed (n = 227), 37.8% said they had cut back or made a change in their smoking habit and 7% had quit in February-March 2013. NEC satisfaction ratings predicted changes in smoking habit and reductions in nicotine dependence after controlling for covariates including demographic variables, factory-made vs. roll-your-own tobacco preference, and addiction scores. CONCLUSION: Smokers' first impressions of NECs were very favourable, and were correlated with readiness to change after a tobacco tax increase. NECs appear to be particularly attractive for female smokers, and their use may help to improve the efficacy of nicotine replacement therapy for women. PMID- 26135335 TI - Separate dimensions of anxiety differentially predict alcohol use among male juvenile offenders. AB - INTRODUCTION: Although research has documented robust prospective relationships between externalizing symptomatology and subsequent adolescent alcohol use, the extent to which internalizing symptoms such as anxiety may increase risk for alcohol consumption remains controversial. Recent evidence suggests that one possible reason for mixed findings is that separate dimensions of anxiety differentially confer risk for alcohol use. The present study tested two dimensions of anxiety, worry and physiological anxiety symptoms, as predictors of alcohol use and misuse in a longitudinal sample of juvenile offenders. METHODS: Participants were 818 male juvenile offenders drawn from a larger multi-site, longitudinal study. Zero-inflated Poisson regression models estimated the influence of anxiety symptoms on typical drinking quantity, frequency of binge drinking, and alcohol dependence symptoms. RESULTS: Results indicate that physiological anxiety and worry symptoms showed differential relations with alcohol use risk. Physiological anxiety was positively associated with increased risk for typical alcohol involvement, frequency of binge drinking, and alcohol dependence symptoms, whereas worry was negatively associated with all alcohol use outcomes. CONCLUSIONS: Current findings underscore the importance of considering anxiety as a multidimensional construct when examining the prospective relation between anxiety and adolescent alcohol use risk. PMID- 26135333 TI - Associations between adrenocortical activity and nicotine response in female smokers by menstrual phase. AB - Previous research suggests that menstrual phase may influence smoking-related symptomatology. The present study analyzes the relationship between menstrual phase and salivary cortisol with subjective responses to nicotine among female smokers during ad libitum smoking. We hypothesize higher cortisol levels would be associated with increased positive and decreased negative subjective responses to nicotine. We also expected that these associations would vary by menstrual phase. Females aged 18-40 who smoke at least five cigarettes/day, reported regular menstrual cycles and did not use exogenous hormones or psychotropic medications were enrolled into a controlled cross-over trial. Participants completed identical data collection procedures during follicular (F) and luteal (L) phases; including self-collected salivary cortisol samples and completion of a nicotine response lab session involving administration of nicotine nasal spray and monitoring of subjective response to nicotine via the Subjective State Scale and Visual Analog Scale. Participants (n = 116) were 29.1 +/- 6.9 years old and smoked an average of 12.3 +/- 5.5 cigarettes daily. During F phase, higher morning cortisol was associated with decreased negative affect (r = -0.21, p = 0.03), withdrawal (r = -0.30, p < 0.01) and increased relaxation (r = 0.24, p = 0.02) after administration of nicotine nasal spray. Conversely, during L phase, higher morning cortisol was associated with a decrease in head rush (r = -0.26, p = 0.01) and urge to smoke (r = -0.21, p = 0.04) after administration of nicotine nasal spray. Similar associations between greater diurnal cortisol variation and response to nicotine were seen. These observations indicate that cortisol may have a phase-specific association with some subjective responses to nicotine in female smokers. Additional research should explore how these relationships may influence smoking cessation efforts. PMID- 26135336 TI - Risk and protective factors for recreational and hard drug use among Malaysian adolescents and young adults. AB - INTRODUCTION: This study investigated risk and protective factors for recreational and hard drug use in Malaysian adolescents and young adults. METHODS: Participants (n = 859; M age = 17.24 years, SD = 2.75 years, range = 13 25 years; 59% male) were recruited from secondary schools, technical colleges, a juvenile detention center and a national training center in Malaysia. A version of the Communities That Care survey validated for use in Malaysia (Razali & Kliewer, 2015) was used to assess study constructs. RESULTS: One in 6 adolescents and 1 in 3 young adults reported lifetime recreational and hard drug use, with greater use reported by males across all drug categories. Structural equation modeling was used to determine the strongest risk and protective factors for recreational and hard drug use. The overall pattern of findings was similar for recreational and hard drug use. Shared risk factors for lifetime recreational and hard drug use included early initiation of antisocial behavior, peer antisocial behavior, and peer reinforcement for engaging in antisocial behavior; shared protective factors included religious practices and opportunities for prosocial school involvement. Multiple group analyses comparing adolescents and young adults indicated that patterns of risk and protective factors predicting drug use differed across these age groups. There were fewer significant predictors of either recreational or hard drug use for young adults relative to adolescents. CONCLUSIONS: Results suggest that interventions should target multiple microsystems (e.g., peer groups, family systems, school environments) and be tailored to the developmental stage of the individual. PMID- 26135337 TI - Asthma deaths in children in New South Wales 2004-2013: Could we have done more? AB - AIMS: The aim of this study was to characterise the deaths of children from asthma in New South Wales (NSW) over the last 10 years and ascertain whether there were modifiable factors that could have prevented the deaths. METHODS: The hospital medical records, coronial reports, immunisation records and all relevant correspondence from general practitioners, medical specialists and hospitals were reviewed for children who died with asthma in the 10 years (2004-2013). RESULTS: In 10 years, there were 20 deaths (0-7 per year) with a male predominance (70%) occurring in children aged 4-17 years. Sixteen (80%) had persistent asthma and 4 (20%) had intermittent asthma. The majority (55%) had been hospitalised for asthma in the preceding 12 months, 25% in the preceding 6 weeks. The majority (55%) was aged 10-14 years. Ninety percent were atopic. Psychosocial issues were identified in the majority (55%) of families. Forty percent had a child protection history. Seventy-five percent had consulted a general practitioner in the year before their death, 45% had a current written asthma action plan and 50% had not seen a paediatrician ever in relation to their asthma. Of the 16 children at school, the schools were aware of the asthma in 14 (88%) cases, but only half had copies of written asthma plans. CONCLUSIONS: Improved communication and oversight between health-care providers, education and community protection agencies could reduce mortality from asthma in children. PMID- 26135338 TI - A Slowly Enlarging Tumor on a Child's Leg. PMID- 26135339 TI - Compound droplet manipulations on fiber arrays. AB - Recent works demonstrated that fiber arrays may constitute new means of designing open digital microfluidic systems. Various processes, such as droplet motion, fragmentation, trapping, release, mixing and encapsulation, may be achieved on fiber arrays. However, handling a large number of tiny droplets resulting from the mixing of several liquid components is required for developing microreactors, smart sensors or microemulsifying drugs. Here, we show that the manipulation of tiny droplets onto fiber networks allows for creating compound droplets with a high complexity level. Moreover, this cost-effective and adjustable method may also be implemented with optical fibers in order to develop fluorescence-based biosensor. PMID- 26135340 TI - QSAR of Chalcones Utilizing Theoretical Molecular Descriptors. AB - The paper is an attempt for QSAR modeling based on topological, electrostatic, quantum chemical, constitutional, geometrical and physicochemical indices computed from the structures of 59 set of synthesized chalcone derivatives tested for the cell cycle inhibition of mitotic G2/M phase using multiple linear regression method. Impact of such computed structural descriptors towards antimitotic and antiproliferative activities was analysed by ridge regression (RR) studies. The RR model explained that the topological indices alone can produce significant influence upon the pharmacological responses while combination of topological, electrostatic and quantum chemical descriptors can enhance the degree of impact towards antimitotic and antiproliferative activities of these compounds. Furthermore, QSAR models were formulated utilizing only topological and the combination of topological, electrostatic and quantum chemical descriptors respectively by multiple linear regression method and the validation of the model was performed by searching the predictability of the QSAR models. Satisfactory results were obtained in terms of model quality expressed as R(2) = 0.826, QLoo(2) = 0.710, Rpred(2) = 0.771 respectively for the topological indices. Combination of topological, electrostatic and quantum chemical descriptors resulted in an increase of R(2) = 0.965, QLoo 2 = 0.891, Rpred(2) = 0.849. The generated model predicted that BCUT descriptors (Charge) using modified partial equalization of orbital electronegativity (MPEOE), autocorrelation descriptors, information content descriptor and HOMO descriptor are very much crucial for modeling highly active chalcone compounds. Quantitative structure-activity relationships modeling of 59 set of synthesized chalcone derivatives were tested for the inhibition of mitotic G2/M phase using ridge regression and multiple linear regression methodologies. The generated model predicted that BCUT descriptors (Charge) using modified partial equalization of orbital electronegativity (MPEOE), autocorrelation descriptors, information content descriptor and HOMO descriptor are very much crucial for producing mitotic spindle inhibition of chalcone compounds. PMID- 26135341 TI - A Structure Guided QSAR: A Rapid and Accurate technique to predict IC50: A Case Study. AB - In this study, the role of highly structured water molecules present in the active site of the leukotriene A4 hydrolase (LTA4H) enzyme has been critically examined through the docking experiments. It was observed that different experiments were necessary to perform the docking studies. The ligands capable of displacing or interacting with bound-water(s) displayed different binding poses as well as the scores. The docking scores E (CvdW) from Glide and ChemScore (CS) from FlexX, with and without bound-waters, obtained through different docking experiments were used to construct two structure guided bi-parametric linear regression models using the IC50 enzyme activity data. The predictive squared correlation coefficients (Q(2)) obtained for these models, with and without bound waters, were found to be 0.73 and 0.67, respectively. These models were validated using test and validated sets of compounds. Utilizing these QSAR models, 409 proposed structures were docked and their respective predicted IC50 data were generated. From the in-silico evaluation of these 409 proposed structures representing diverse chemotypes, 39 compounds were triaged, synthesized and evaluated in the enzyme inhibition assay. The predicted and experimental biological data (IC50) was correlated and the square of the correlation coefficient (R(2)) between the observed and calculated IC50 was found to be 0.87. PMID- 26135342 TI - Insight into the Binding of DFG-out Allosteric Inhibitors to B-Raf Kinase Using Molecular Dynamics and Free Energy Calculations. AB - B-Raf mutations are identified in 40-50% of patients with melanoma and among them, the substitution of valine for glutamic acid at position 600 ((V600E)B-Raf) is the most frequent. Treatment of these patients with B-Raf inhibitors has been associated with a clear clinical benefit. Unfortunately, multiple resistance mechanisms have been identified and new potent and selective inhibitors are currently needed. In this work, five different type II inhibitors, which bind (V600E)B-Raf in its DFG-out conformation, have been studied using molecular dynamics, free energy calculations and energy decomposition analysis. The ranking of calculated MM-PB/GBSA binding affinities is in good agreement with the experimentally measured ones. The per-residue decomposition of DeltaGbinding, within the MM-GBSA approach, has been used to identify the key residues governing the allosteric binding of the studied compounds to the (V600E)B-Raf protein kinase. Results indicate that although van der Waals interactions are key determinants for binding, hydrogen bonds also play an important role. This work also provides a better structural understanding of the binding of DFG-out inhibitors to (V600E)B-Raf, which can be used in a further step for rational design of a new class of B-Raf potent inhibitors. PMID- 26135343 TI - N2 activation by an iron complex with a strong electron-donating iminophosphorane ligand. AB - A new tridentate cyclopentane-bridged iminophosphorane ligand, N-(2 diisopropylphosphinophenyl)-P,P-diisopropyl-P-(2-(2,6 diisopropylphenylamido)cyclopent-1-enyl)phosphoranimine (NpNPiPr), was synthesized and used in the preparation of a diiron dinitrogen complex. The reaction of the iron complex FeBr(NpNPiPr) with KC8 under dinitrogen yielded the dinuclear dinitrogen Fe complex [Fe(NpNPiPr)]2(MU-N2), which was characterized by X-ray analysis and resonance Raman and NMR spectroscopies. The X-ray analysis revealed a diiron complex bridged by the dinitrogen molecule, with each metal center coordinated by an NpNPiPr ligand and dinitrogen in a trigonal monopyramidal geometry. The N-N bond length is 1.184(6) A, and resonance Raman spectra indicate that the N-N stretching mode nu(14N2/15N2) is 1755/1700 cm-1. The magnetic moment of [Fe(NpNPiPr)]2(MU-N2) in benzene-d6 solution, as measured by 1H NMR spectroscopy by the Evans method, is 6.91MUB (S = 3). The Mossbauer spectrum at 78 K showed delta = 0.73 mm/s and DeltaEQ = 1.83 mm/s. These findings suggest that the iron ions are divalent with a high-spin configuration and that the N2 molecule has (N?N)2- character. Density functional theory calculations performed on [Fe(NpNPiPr)]2(MU-N2) also suggested that the iron is in a high-spin divalent state and that the coordinated dinitrogen molecule is effectively activated by pi back-donation from the two iron ions (dpi) to the dinitrogen molecule (pix* and piy*). This is supported by cooperation between a large negative charge on the iminophosphorane ligand and strong electron donation and effective orbital overlap between the iron dpi orbitals and N2 pi* orbitals supplied by the phosphine ligand. PMID- 26135344 TI - Maternal prepregnancy waist circumference and BMI in relation to gestational weight gain and breastfeeding behavior: the CARDIA study. AB - BACKGROUND: Studies suggest that gestational weight gain (GWG) and breastfeeding behavior may influence long-term maternal abdominal fat mass. However, this could be confounded by abdominal fat mass before pregnancy because it is unknown whether abdominal fat mass, independently of body size, affects GWG and breastfeeding behavior. OBJECTIVE: We investigated how maternal prepregnancy fat distribution, described by waist circumference (WC) and body mass index (BMI), is associated with GWG and breastfeeding behavior. DESIGN: We analyzed 1371 live births to 1024 women after enrollment in the Coronary Artery Risk Development in Young Adults study (1985-1996). For each birth, maternal prepregnancy BMI and WC were measured at year 0 (baseline), 2, 5, or 7 examinations. Recalled GWG and breastfeeding behavior were collected at years 7 and 10. GWG was analyzed by using linear regression and breastfeeding behavior by using logistic regression and discrete-time logistic regression. RESULTS: Adjusted for potential confounders, a 1-cm larger WC adjusted for BMI was associated with a 0.19-kg (95% CI: -0.29-, -0.10-kg) lower GWG. In contrast, a 1-unit higher BMI adjusted for WC was associated with a 0.27-kg (95% CI: 0.06-, 0.47-kg) higher GWG. The OR for ever breastfeeding compared with never breastfeeding was 0.93 (95% CI: 0.90, 0.97) per 1-cm larger WC after adjustment for BMI, whereas it was 1.10 (95% CI: 1.02, 1.19) per 1-unit higher BMI adjusted for WC. CONCLUSIONS: Maternal prepregnancy body size was differently associated with GWG and breastfeeding behavior depending on the location of the fat mass. Thus, maternal fat distribution may be a more important determinant of GWG and breastfeeding behavior than BMI alone. PMID- 26135345 TI - Health effects of intermittent fasting: hormesis or harm? A systematic review. AB - BACKGROUND: Intermittent fasting, alternate-day fasting, and other forms of periodic caloric desistance are gaining popularity in the lay press and among animal research scientists. Whether clinical evidence exists for or is strong enough to support the use of such dietary regimens as health interventions is unclear. OBJECTIVE: This review sought to identify rigorous, clinically relevant research studies that provide high-quality evidence that therapeutic fasting regimens are clinically beneficial to humans. DESIGN: A systematic review of the published literature through January 2015 was performed by using sensitive search strategies to identify randomized controlled clinical trials that evaluated the effects of fasting on either clinically relevant surrogate outcomes (e.g., weight, cholesterol) or actual clinical event endpoints [e.g., diabetes, coronary artery disease (CAD)] and any other studies that evaluated the effects of fasting on clinical event outcomes. RESULTS: Three randomized controlled clinical trials of fasting in humans were identified, and the results were published in 5 articles, all of which evaluated the effects of fasting on surrogate outcomes. Improvements in weight and other risk-related outcomes were found in the 3 trials. Two observational clinical outcomes studies in humans were found in which fasting was associated with a lower prevalence of CAD or diabetes diagnosis. No randomized controlled trials of fasting for clinical outcomes were identified. CONCLUSIONS: Clinical research studies of fasting with robust designs and high levels of clinical evidence are sparse in the literature. Whereas the few randomized controlled trials and observational clinical outcomes studies support the existence of a health benefit from fasting, substantial further research in humans is needed before the use of fasting as a health intervention can be recommended. PMID- 26135346 TI - Dietary magnesium and potassium intakes and circulating magnesium are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the EPIC Norfolk cohort study. AB - BACKGROUND: In our aging population, maintenance of bone health is critical to reduce the risk of osteoporosis and potentially debilitating consequences of fractures in older individuals. Among modifiable lifestyle and dietary factors, dietary magnesium and potassium intakes are postulated to influence bone quality and osteoporosis, principally via calcium-dependent alteration of bone structure and turnover. OBJECTIVE: We investigated the influence of dietary magnesium and potassium intakes, as well as circulating magnesium, on bone density status and fracture risk in an adult population in the United Kingdom. DESIGN: A random subset of 4000 individuals from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of 25,639 men and women with baseline data was used for bone density cross-sectional analyses and combined with fracture cases (n = 1502) for fracture case-cohort longitudinal analyses (mean follow-up 13.4 y). Relevant biological, lifestyle, and dietary covariates were used in multivariate regression analyses to determine associations between dietary magnesium and potassium intakes and calcaneal broadband ultrasound attenuation (BUA), as well as in Prentice-weighted Cox regression to determine associated risk of fracture. Separate analyses, excluding dietary covariates, investigated associations of BUA and fractures with serum magnesium concentration. RESULTS: Statistically significant positive trends in calcaneal BUA for women (n = 1360) but not men (n = 968) were apparent across increasing quintiles of magnesium plus potassium (Mg+K) z score intake (P = 0.03) or potassium intake alone (P = 0.04). Reduced hip fracture risk in both men (n = 1958) and women (n = 2755) was evident for individuals in specific Mg+K z score intake quintiles compared with the lowest. Statistically significant trends in fracture risk in men across serum magnesium concentration groups were apparent for spine fractures (P = 0.02) and total hip, spine, and wrist fractures (P = 0.02). None of these individual statistically significant associations remained after adjustment for multiple testing. CONCLUSIONS: These findings enhance the limited literature studying the association of magnesium and potassium with bone density and demonstrate that further investigation is warranted into the mechanisms involved and the potential protective role against osteoporosis. PMID- 26135347 TI - Does fortification of staple foods improve vitamin D intakes and status of groups at risk of deficiency? A United Kingdom modeling study. AB - BACKGROUND: More than one-fifth of the United Kingdom population has poor vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] concentration <25 nmol/L), particularly individuals with low sun exposure or poor dietary intake. OBJECTIVE: We identified the fortification vehicle and concentration most likely to safely increase population vitamin D intakes and vitamin D status. DESIGN: Wheat flour and milk were identified as primary fortification vehicles for their universal consumption in population groups most at risk of vitamin D deficiency including children aged 18-36 mo, females aged 15-49 y, and adults aged >=65 y. With the use of data from the first 2 y (2008-2010) of the National Diet and Nutrition Survey Rolling Program, we simulated the effect of fortifying wheat flour and milk with vitamin D on United Kingdom food consumption. Empirically derived equations for the relation between vitamin D intake and the serum 25(OH)D concentration were used to estimate the population serum 25(OH)D concentration for each fortification scenario. RESULTS: At a simulated fortification of 10 MUg vitamin D/100 g wheat flour, the proportion of at-risk groups estimated to have vitamin D intakes below United Kingdom Reference Nutrient Intakes was reduced from 93% to 50%, with no individual exceeding the United Kingdom Tolerable Upper Intake Level; the 2.5th percentile of the population winter serum 25(OH)D concentration rose from 20 to 27 nmol/L after fortification. The simulation of the fortification of wheat flour at this concentration was more effective than that of the fortification of milk (at concentrations between 0.25 and 7 mg vitamin D/100 L milk) or of the fortification of milk and flour combined. CONCLUSION: To our knowledge, this study provides new evidence that vitamin D fortification of wheat flour could be a viable option for safely improving vitamin D intakes and the status of United Kingdom population groups at risk of deficiency without increasing risk of exceeding current reference thresholds. PMID- 26135348 TI - Absence of an effect of high nitrate intake from beetroot juice on blood pressure in treated hypertensive individuals: a randomized controlled trial. AB - BACKGROUND: Dietary nitrate, which is in green leafy vegetables and beetroot, decreases blood pressure through the enterosalivary nitrate-nitrite-nitric oxide pathway in healthy individuals. Whether similar effects would occur in individuals with treated hypertension and, therefore, at increased risk of cardiovascular disease is unclear. OBJECTIVE: We assessed whether increased dietary nitrate intake by using beetroot juice for 1 wk lowers blood pressure in treated hypertensive men and women. DESIGN: Participants (n = 27) were recruited to a randomized, placebo-controlled, double-blind crossover trial. The effect of 1-wk intake of nitrate-rich beetroot juice was compared with 1-wk intake of nitrate-depleted beetroot juice (placebo). The primary outcome was blood pressure assessed by measuring home blood pressure during the intervention and 24-h ambulatory blood pressure on day 7 of the intervention. Other outcomes included nitrate metabolism assessed by measuring nitrate and nitrite in plasma, saliva, and urine. RESULTS: Relative to the placebo, 1-wk intake of nitrate-rich beetroot juice resulted in a 3-fold increase in plasma nitrite and nitrate, a 7-fold increase in salivary nitrite, an 8-fold higher salivary nitrate, and a 4-fold increase in both urinary nitrite and nitrate (P < 0.001). However, no differences in home blood pressure and 24-h ambulatory blood pressure were observed with 1-wk intake of nitrate-rich beetroot juice in comparison with the placebo. CONCLUSION: An increase in dietary nitrate intake may not be an effective short-term approach to further lower blood pressure in treated hypertensive subjects. PMID- 26135349 TI - Butter increased total and LDL cholesterol compared with olive oil but resulted in higher HDL cholesterol compared with a habitual diet. AB - BACKGROUND: Butter is known to have a cholesterol-raising effect and, therefore, has often been included as a negative control in dietary studies, whereas the effect of moderate butter intake has not been elucidated to our knowledge. OBJECTIVE: We compared the effects of moderate butter intake, moderate olive oil intake, and a habitual diet on blood lipids, high-sensitivity C-reactive protein (hsCRP), glucose, and insulin. DESIGN: The study was a controlled, double blinded, randomized 2 * 5-wk crossover dietary intervention study with a 14-d run in period during which subjects consumed their habitual diets. The study included 47 healthy men and women (mean +/- SD total cholesterol: 5.22 +/- 0.90 mmol/L) who substituted a part of their habitual diets with 4.5% of energy from butter or refined olive oil. RESULTS: Study subjects were 70% women with a mean age and body mass index (in kg/m2) of 40.4 y and 23.5, respectively. Butter intake increased total cholesterol and LDL cholesterol more than did olive oil intake (P < 0.05) and the run-in period (P < 0.005 and P < 0.05, respectively) and increased HDL cholesterol compared with the run-in period (P < 0.05). No difference in effects was observed for triacylglycerol, hsCRP, insulin, and glucose concentrations. The intake of saturated fatty acids was significantly higher in the butter period than in the olive oil and run-in periods (P < 0.0001). CONCLUSIONS: Moderate intake of butter resulted in increases in total cholesterol and LDL cholesterol compared with the effects of olive oil intake and a habitual diet (run-in period). Furthermore, moderate butter intake was also followed by an increase in HDL cholesterol compared with the habitual diet. We conclude that hypercholesterolemic people should keep their consumption of butter to a minimum, whereas moderate butter intake may be considered part of the diet in the normocholesterolemic population. PMID- 26135350 TI - Dietary polyamine intake and colorectal cancer risk in postmenopausal women. AB - BACKGROUND: Putrescine, spermidine, and spermine (i.e., polyamines) are small cationic amines synthesized by cells or acquired from the diet or gut bacteria. Polyamines are required for both normal and colorectal cancer (CRC) cell growth. OBJECTIVE: We investigated the association between dietary polyamines and risk of CRC incidence and mortality. DESIGN: The study was a prospective analysis in 87,602 postmenopausal women in the Women's Health Initiative Observational Study. Multivariate Cox regression was used to calculate HRs and 95% CIs. RESULTS: Total dietary polyamine intake (mean +/- SD: 289.2 +/- 127.4 MUmol/d) was not positively associated with CRC in fully adjusted models. Instead, intake >=179.67 MUmol/d was associated with reduced risk of CRC [HR (95% CI): 0.82 (0.68, 1.00), 0.81 (0.66, 0.99), 0.91 (0.74, 1.12), and 0.80 (0.62, 1.02) for quintiles 2-5, respectively, compared with quintile 1]. Reduced risk was not significant across all quintiles. Polyamines were not significantly associated with CRC-specific mortality in fully adjusted models. When stratified by risk factors for CRC, only body mass index (BMI) and fiber intake significantly modified the association between polyamine intake and CRC. In women with BMI (in kg/m2) <=25 or fiber consumption above the median, polyamine intake was associated with significantly lower risk of CRC. CONCLUSIONS: No positive association between dietary polyamines and CRC or CRC-specific mortality risk in women was observed. Instead, a protective effect of dietary polyamines was suggested in women with some CRC risk-lowering behaviors in particular. These results are consistent with emerging evidence that exogenous polyamines may be beneficial in colon health and warrant additional study. PMID- 26135352 TI - Can D-Dimer Measurement Reduce the Frequency of Radiological Assessment in Patients Receiving Palliative Imatinib for Gastrointestinal Stromal Tumor (GIST)? AB - Imatinib therapy has improved outcomes in advanced GISTs. Current guidelines suggest monitoring with CT scanning every 12 weeks. There are no validated biomarkers to assist disease evaluation. We identified 50 patients treated with imatinib for GIST in a single tertiary center. We assessed the prognostic value of D-dimers by Cox regression, and the utility as a biomarker for radiological progression (rPD) using receiver-operator curve (ROC) analysis. In asymptomatic patients with D-dimer levels <1,000 and falling levels, the negative predictive value for rPD was 92%. D-dimers may reduce the burden of CT scanning in a proportion of patients in this setting. PMID- 26135351 TI - Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial. AB - BACKGROUND: Moderate vitamin B-12 deficiency is relatively common in older people. However, there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life. OBJECTIVE: We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12-deficient older people. DESIGN: We conducted a double-blind, randomized, placebo-controlled trial in 7 general practices in South East England, United Kingdom. Study participants were aged >=75 y and had moderate vitamin B-12 deficiency (serum vitamin B-12 concentrations: 107-210 pmol/L) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo. Peripheral motor and sensory nerve conduction, central motor conduction, a clinical neurologic examination, and cognitive function were assessed before and after treatment. RESULTS: A total of 201 participants were enrolled in the trial, and 191 subjects provided outcome data. Compared with baseline, allocation to vitamin B-12 was associated with a 177% increase in serum concentration of vitamin B-12 (641 compared with 231 pmol/L), a 331% increase in serum holotranscobalamin (240 compared with 56 pmol/L), and 17% lower serum homocysteine (14.2 compared with 17.1 MUmol/L). In intention-to-treat analysis of covariance models, with adjustment for baseline neurologic function, there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo (mean difference: -0.2 mV; 95% CI: -0.8, 0.3 mV). There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome, or on cognitive function or clinical examination. CONCLUSION: Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency, in the absence of anemia and of neurologic and cognitive signs or symptoms, has beneficial effects on neurologic or cognitive function in later life. This trial was registered at www.isrctn.com as ISRCTN54195799. PMID- 26135353 TI - Interaction of AIM with insulin-like growth factor-binding protein-4. AB - Apoptosis inhibitor of macrophages (AIM/cluster of differentiation 5 antigen like/soluble protein alpha) has been shown to inhibit cellular apoptosis; however, the underlying molecular mechanism has not been elucidated. Using yeast two-hybrid screening, the present study uncovered that AIM binds to insulin-like growth factor binding protein-4 (IGFBP-4). AIM interaction with IGFBP-4, as well as IGFBP-2 and -3, but not with IGFBP-1, -5 and -6, was further confirmed by co immunoprecipitation (co-IP) using 293 cells. The binding activity and affinity between AIM and IGFBP-4 in vitro were analyzed by co-IP and biolayer interferometry. Serum depletion-induced cellular apoptosis was attenuated by insulin-like growth factor-I (IGF-I), and this effect was abrogated by IGFBP-4. Of note, in the presence of AIM, the inhibitory effect of IGFBP-4 on the anti apoptosis function of IGF-I was attenuated, possibly through binding of AIM with IGFBP-4. In conclusion, to the best of our knowledge, the present study provides the first evidence that AIM binds to IGFBP-2, -3 and -4. The data suggest that this interaction may contribute to the mechanism of AIM-mediated anti-apoptosis function. PMID- 26135354 TI - The balance between adaptive and apoptotic unfolded protein responses regulates beta-cell death under ER stress conditions through XBP1, CHOP and JNK. AB - Endoplasmic reticulum (ER) stress and the subsequent unfolded protein response (UPR) have been implicated in beta-cell death in type 1 and type 2 diabetes. However, the UPR is also a fundamental mechanism required for beta-cell adaptation and survival. The mechanisms regulating the transition from adaptive to apoptotic UPR remain to be clarified. Here, we investigated the relationships between XBP1, CHOP and JNK in the transition from adaptive to apoptotic UPR and beta-cell death in models of type 1 and type 2 diabetes. XBP1 inhibition potentiated cell death induced by pro-inflammatory cytokines or the saturated fatty acid palmitate in MIN6 beta-cells. This response was prevented by CHOP inhibition. IRE1/XBP1 inhibition led to alterations in islets from diabetes resistant ob/ob mice that resemble those found in diabetes, including increases in cell death and inflammation and antioxidant gene expression. Similarly, IRE1/XBP1 inhibition increased cell death in islets from NOD mice. On the other hand, JNK inhibition: 1) increased adaptive UPR and reduced cell death in islets from diabetic db/db mice, and 2) restored adaptive UPR while protecting against apoptotic UPR gene expression and beta-cell death and dysfunction following cytokine exposure. These findings suggest that the balance between XBP1-mediated adaptive and CHOP-dependent apoptotic UPR is critically important for beta-cell survival during ER stress. JNK activation regulates the transition from adaptive to apoptotic UPR, thus providing a mechanism for beta-cell propensity to cell death rather than ER stress adaptation in type 1 and type 2 diabetes. PMID- 26135355 TI - Fifteen-minute consultation: when is a seizure not a seizure? Part 1, the younger child. AB - Paroxysmal non-epileptic events (PNEs) are common, and occur in all age groups ranging from neonates to young adults. The key to diagnosis in the majority is a detailed history and careful observation. However, a few can pose diagnostic challenges for the paediatrician to differentiate them from epileptic seizures. PNEs are usually recurrent, stereotyped and some of them tend to repeatedly occur within the same context. Although the vast majority have a benign nature, they can be a source of parental anxiety, unnecessary investigations and even potentially harmful treatments. In this review, we have described the common PNEs occurring in infants and preschool children. This will be followed by a second review for older children and adolescents. We have provided a practical diagnostic approach by dividing these events into three broad categories: PNEs associated with altered consciousness, PNEs not associated with apparently altered consciousness and sleep-related PNEs. PMID- 26135356 TI - Fifteen-minute consultation: when is a seizure not a seizure? Part 2, the older child. AB - Paroxysmal non-epileptic events (PNEs) refer to episodic changes in behaviour, sensation or consciousness that lead to unusual movements, which may resemble epileptic seizures, but are not, due to excessive neuronal firing in the cerebral cortex. A significant proportion of patients seen in epilepsy clinics do not actually have epilepsy. Therefore, it is paramount for clinicians to be able to recognise these transient non-epileptic events in order to avoid unnecessary antiepileptic treatments and to provide appropriate management as required. These PNEs can be observed within the context of a neurological disorder such as migraine or with no direct neurological basis such as simple tics. In this review, we have described common PNEs presenting in school-age children and adolescents alongside the clinical approach to differentiate them from epileptic seizures. PNEs occurring in infancy and younger children have been covered in our first review of this series. PMID- 26135357 TI - Shorter, rough trunnion surfaces are associated with higher taper wear rates than longer, smooth trunnion surfaces in a contemporary large head metal-on-metal total hip arthroplasty system. AB - Taper wear at the head-neck junction is a possible cause of early failure in large head metal-on-metal (LH-MoM) hip replacements. We hypothesized that: (i) taper wear may be more pronounced in certain product designs; and (ii) an increased abductor moment arm may be protective. The tapers of 104 explanted LH MoM hip replacements revised for adverse reaction to metal debris (ARMD) from a single manufacturer were analyzed for linear and volumetric wear using a co ordinate measuring machine. The mated stem was a shorter 12/14, threaded trunnion (n=72) or a longer, smooth 11/13 trunnion (n=32). The abductor moment arm was calculated from pre-revision radiographs. Independent predictors of linear and volumetric wear included taper angle, stem type, and the horizontal moment arm. Tapers mated with the threaded 12/14 trunnion had significantly higher rates of volumetric wear (0.402 mm3/yr vs. 0.123 mm3/yr [t=-2.145, p=0.035]). There was a trend to larger abductor moment arms being protective (p=0.055). Design variation appears to play an important role in taper-trunnion junction failure. We recommend that surgeons bear these findings in mind when considering the use of a short, threaded trunnion with a cobalt-chromium head. PMID- 26135359 TI - Surface Enhanced Resonance Raman Spectroscopy Reveals Potential Induced Redox and Conformational Changes of Cytochrome c Oxidase on Electrodes. AB - Immobilization of Cytochrome c oxidase (CcO) on electrodes makes voltage-driven reduction of oxygen to water possible. Efficient catalytic turnover in CcO/electrode systems is, however, often observed at large overpotentials that cannot be rationalized by the redox properties of the enzyme itself. To understand the structural basis for this observation, CcO was electrostatically adsorbed on amino-functionalized Ag electrodes, and the redox transitions of heme a and a3 were monitored via surface enhanced resonance Raman spectroscopy (SERRS) as a function of applied potential. Under completely anaerobic conditions, the reduction of heme a3 could be seen at potentials close to those measured in solution indicating an intact catalytic center. However, in the immobilized state, a new non-native heme species was observed that exhibited a redox potential much more negative than measured for the native hemes. Analysis of the high and low frequency SERR spectra indicated that this new species is formed from heme a upon axial loss of one histidine ligand. It is concluded that the formation of the non-native heme a species alters the potential-dependent electron supply to the catalytic reaction and, thus, can have a impact on the applicability of this enzyme in biofuel cells. PMID- 26135360 TI - Developments in inhaled combination therapies: patent activity 2013-2014. AB - INTRODUCTION: Since the 1970s, the treatment options for asthma and chronic obstructive pulmonary disease have increasingly relied upon the use of inhaled drug formulations, generally from handheld inhaler devices. The introduction of combinations of a corticosteroid with a long-acting beta2 agonist has dramatically transformed the accepted treatment paradigm. This has led to a dramatic increase in the development of novel combinations of inhaled drugs, including long-acting muscarinic antagonists with long-acting beta2 agonists, as well as triple combinations, and of devices for their delivery. AREAS COVERED: This review considers recent patent filings claiming inhaled drug combinations, or devices delivering them, that are useful in the treatment of asthma and/or chronic obstructive pulmonary disease. EXPERT OPINION: The modest level of activity in patent filings relating to inhaled combinations is surprising. Many of the patents are from the major players in the respiratory market segment, with only one inhalation technology specialist showing significant activity. The limited activity from generics companies is explained by the limited range of active ingredients whose use they can usefully claim. PMID- 26135361 TI - Thermo-solutal and kinetic regimes of an anisotropic dendrite growing under forced convective flow. AB - A thermo-diffusional problem of a free dendrite growing in a binary mixture is considered analytically. Effects of the anisotropy and convective flow on the stable mode of the dendrite with four-fold crystal symmetry are studied. Special analysis is given for the parabolic dendrite growing at arbitrary Peclet numbers and with small anisotropy of surface energy and atomic kinetics. The stable growth mode is analyzed through the solvability condition giving the stability criterion for the dendrite tip velocity V and dendrite tip diameter rho as a function of growth Peclet number, Pg, flow Peclet number, Pf, and Reynolds number, Re. Using the obtained criterion of stability, a complete sequence of transitions in growth regimes (namely, from solute diffusion-limited to thermally controlled and further to kinetically-limited regimes) of the anisotropic dendrite is derived and revealed. Limiting cases to known criteria for small and high growth Peclet numbers of the solidifying system with and without convective fluid flow are found. Two-dimensional solidification regimes and scalings obtained are discussed for their extension to three-dimensional dendritic growth. PMID- 26135358 TI - Bacillithiol has a role in Fe-S cluster biogenesis in Staphylococcus aureus. AB - Staphylococcus aureus does not produce the low-molecular-weight (LMW) thiol glutathione, but it does produce the LMW thiol bacillithiol (BSH). To better understand the roles that BSH plays in staphylococcal metabolism, we constructed and examined strains lacking BSH. Phenotypic analysis found that the BSH deficient strains cultured either aerobically or anaerobically had growth defects that were alleviated by the addition of exogenous iron (Fe) or the amino acids leucine and isoleucine. The activities of the iron-sulfur (Fe-S) cluster dependent enzymes LeuCD and IlvD, which are required for the biosynthesis of leucine and isoleucine, were decreased in strains lacking BSH. The BSH-deficient cells also had decreased aconitase and glutamate synthase activities, suggesting a general defect in Fe-S cluster biogenesis. The phenotypes of the BSH-deficient strains were exacerbated in strains lacking the Fe-S cluster carrier Nfu and partially suppressed by multicopy expression of either sufA or nfu, suggesting functional overlap between BSH and Fe-S carrier proteins. Biochemical analysis found that SufA bound and transferred Fe-S clusters to apo-aconitase, verifying that it serves as an Fe-S cluster carrier. The results presented are consistent with the hypothesis that BSH has roles in Fe homeostasis and the carriage of Fe-S clusters to apo-proteins in S. aureus. PMID- 26135362 TI - Behaviours and opinions towards outdoor smoking bans and cigarette littering in Baja California, Mexico. AB - OBJECTIVE: Outdoor smoking bans have been implemented to reduce secondhand smoke exposure and cigarette littering. We aimed to explore outdoor smoking behaviours, cigarette littering, and support towards a recently enacted outdoor smoking ban in Baja California, Mexico. METHODS: From October 2013 to April 2014 a representative sample of 800 adults from urban areas of Baja California was surveyed to obtain information on demographics, smoking status, opinion towards outdoor smoking bans in general and in specific locations, and perceptions and habits regarding cigarette littering. Descriptive statistics and Poisson regression analyses were conducted to estimate prevalence ratios and corresponding 95% CI taking into account the complex survey design. RESULTS: Outdoor smoking was frequently observed, as 86.8% of the population reported having seen people smoking in parks and beaches and 94.4% in open venues such as concerts or stadiums. A smoking ban in all outdoor areas was supported by 71.8% of Baja California residents. Site-specific support ranged from 80% (stadiums) to 89% (public parks). Support for the ban was higher among never and ex-smokers than in current smokers. Cigarette littering was negatively perceived by 98% of the participants, yet 45% of all cigarettes smoked were thrown on the ground. Based on cigarette consumption and butt littering reported in the survey, we estimated that 27 million cigarette butts become litter every month in urban areas of Baja California. CONCLUSIONS: Outdoor smoking is still frequent in outdoor areas where people gather, and an important source of littering. We found substantial public support towards the outdoor smoking ban, which should translate into easier implementation and compliance in Baja California, Mexico. PMID- 26135363 TI - Improving referrals and integrating family planning and HIV services through organizational network strengthening. AB - BACKGROUND: The service needs of people with human immunodeficiency virus (HIV) in low-income settings are wide-ranging. Service provision in a community is often disjointed among a variety of providers. We sought to reduce unmet patient needs by increasing referral coordination for HIV and family planning, measured as network density, with an organizational network approach. METHODS: We conducted organizational network analysis on two networks in sub-cities of Addis Ababa, Ethiopia. There were 25 organizations in one sub-city network and 26 in the other. In one of them we sought to increase referrals through three network strengthening meetings. We then conducted the network analysis again in both sub cities to measure any changes since baseline. We also quantitatively measured reported client service needs in both sub-cities before and after the intervention with two cross-sectional samples of face-to-face interviews with clients (459 at baseline and 587 at follow-up). RESULTS: In the sub-city with the intervention, the number of referral connections between organizations, measured as network density, increased 55%. In the control community, the density decreased over the same period. Reported unmet client service needs declined more consistently across services in the intervention community. DISCUSSION: This quasi experiment demonstrated that (1) an organizational network analysis can inform an intervention, (2) a modest network strengthening intervention can enhance client referrals in the network, (3) improvement in client referrals was accompanied by a decrease in atient-reported unmet needs and (4) a series of network analyses can be a useful evaluation tool. PMID- 26135365 TI - Importance of Image Guidance in Glenohumeral Joint Injections: Comparing Rates of Needle Accuracy Based on Approach and Physician Level of Training. AB - OBJECTIVE: This study compared the accuracy of blind glenohumeral joint (GHJ) injections between physical medicine and rehabilitation interventional fellows (inexperienced provider) and a sports medicine board-certified physical medicine and rehabilitation attending physician (experienced provider) using either an anterior or posterior approach. METHODS: A retrospective analysis of 162 consecutive patients comprising 165 GHJ injections was performed. All GHJ injections were initially placed via anatomic landmark guidance by either an experienced or an inexperienced provider. Contrast medium using live fluoroscopy was injected to determine if intra-articular placement had been obtained. RESULTS: The overall accuracy of a blind GHJ injection, regardless of the provider level of experience, was 45.5%. The inexperienced provider was accurate 37.6% of the time, and the experienced provider was accurate 64.6% of the time. The difference in provider accuracy based on level of experience was shown to be statistically significant at P less than 0.05. There was no statistically significant difference between the anterior and posterior approaches regardless of physician level of experience. CONCLUSIONS: The results of this study suggest that image guidance is an important utility for accurate navigation into the GHJ space regardless of the level of training. Neither the anterior nor the posterior approach proved to be significantly more accurate. PMID- 26135364 TI - Factors influencing modes of transport and travel time for obstetric care: a mixed methods study in Zambia and Uganda. AB - Transportation is an important barrier to accessing obstetric care for many pregnant and postpartum women in low-resource settings, particularly in rural areas. However, little is known about how pregnant women travel to health facilities in these settings. We conducted 1633 exit surveys with women who had a recent facility delivery and 48 focus group discussions with women who had either a home or a facility birth in the past year in eight districts in Uganda and Zambia. Quantitative data were analysed using univariate statistics, and qualitative data were analysed using thematic content analysis techniques. On average, women spent 62-68 min travelling to a clinic for delivery. Very different patterns in modes of transport were observed in the two countries: 91% of Ugandan women employed motorized forms of transportation, while only 57% of women in Zambia did. Motorcycle taxis were the most commonly used in Uganda, while cars, trucks and taxis were the most commonly used mode of transportation in Zambia. Lower-income women were less likely to use motorized modes of transportation: in Zambia, women in the poorest quintile took 94 min to travel to a health facility, compared with 34 for the wealthiest quintile; this difference between quintiles was ~50 min in Uganda. Focus group discussions confirmed that transport is a major challenge due to a number of factors we categorized as the 'three A's:' affordability, accessibility and adequacy of transport options. Women reported that all of these factors had influenced their decision not to deliver in a health facility. The two countries had markedly different patterns of transportation for obstetric care, and modes of transport and travel times varied dramatically by wealth quintile, which policymakers need to take into account when designing obstetric transport interventions. PMID- 26135366 TI - Exercise Training Inhibits the Nogo-A/NgR1/Rho-A Signals in the Cortical Peri infarct Area in Hypertensive Stroke Rats. AB - OBJECTIVE: The aim of this study was to test the hypothesis that exercise training promotes motor recovery after stroke by facilitating axonal remodeling via inhibition of the Nogo-A/NgR1 and Rho-A pathway. DESIGN: A distal middle cerebral artery occlusion model was generated in stroke-prone renovascular hypertensive rats. Stroke-prone renovascular hypertensive rats were randomly divided into a control group, an exercise training group, and a sham group. Motor function was measured using the grip strength test. Axon and myelin remodeling markers, growth-associated protein 43, myelin basic protein, Tau, and amyloid precursor protein were detected by immunofluorescence. The expression of Nogo-A, NgR1, and Rho-A was demonstrated by immunofluorescence and Western blotting in the peri-infarction area at 7, 14, 28, and 52 days after distal middle cerebral artery occlusion. RESULTS: Grip strength was higher in the exercise training group (P < 0.05). Exercise training increased the expression of growth-associated protein 43, myelin basic protein (at 7, 14, and 28 days), and Tau (at 7 and 14 days), and decreased the expression of axonal damage amyloid precursor protein (at 7 and 14 days), compared with the control group. The protein levels of Nogo-A (at 7 and 14 days), NgR1 (at 7, 14, and 28 days), and Rho-A (at 14 and 28 days) were reduced after exercise training. CONCLUSIONS: Exercise training promotes axonal recovery, which is associated with functional improvement after cerebral infarction. Down-regulation of the Nogo-A/NgR1/Rho-A may mediate the axonal remodeling induced by exercise training. PMID- 26135367 TI - Brake response time is significantly impaired after total knee arthroplasty: investigation of performing an emergency stop while driving a car. AB - OBJECTIVE: The objective of this study was to investigate whether total knee arthroplasty (TKA) impairs the ability to perform an emergency stop. DESIGN: An automatic transmission brake simulator was developed to evaluate total brake response time. A prospective repeated-measures design was used. Forty patients (20 left/20 right) were measured 8 days and 6, 12, and 52 wks after surgery. RESULTS: Eight days postoperative total brake response time increased significantly by 30% in right TKA and insignificantly by 2% in left TKA. Brake force significantly decreased by 35% in right TKA and by 25% in left TKA during this period. Baseline values were reached at week 12 in right TKA; the impairment of outcome measures, however, was no longer significant at week 6 compared with preoperative values. Total brake response time and brake force in left TKA fell below baseline values at weeks 6 and 12. Brake force in left TKA was the only outcome measure significantly impaired 8 days postoperatively. CONCLUSION: This study highlights that categorical statements cannot be provided. This study's findings on automatic transmission driving suggest that right TKA patients may resume driving 6 wks postoperatively. Fitness to drive in left TKA is not fully recovered 8 days postoperatively. If testing is not available, patients should refrain from driving until they return from rehabilitation. PMID- 26135368 TI - A Rare Cause of Shoulder Pain: Pseudotumor Deltoideus. PMID- 26135369 TI - Development of an IRT-Based Short Form to Assess Applied Cognitive Function in Outpatient Rehabilitation. AB - OBJECTIVE: Item response theory and computerized adaptive testing methods allow the development of a large calibrated item bank from which different subsets of questions can be selected for administration and scored on a common scale. The objective of this study was to develop an outpatient rehabilitation self-report short form for the Activity Measure for Post-Acute Care Applied Cognition item bank. DESIGN: Using data from a convenience sample of 235 rehabilitation outpatients, item content and item response theory-based test information function parameters were used in item selection. Internal consistency reliability, intraclass correlation coefficient (ICC), and percentage at the lowest (floor) and highest (ceiling) scores were evaluated for the short form and full item bank. RESULTS: A 15-item short form was developed. The internal consistency of the short form was 0.86. The ICC3,1 for the short form and item bank was 0.97 (95% confidence interval, 0.94-0.98). No floor effects were noted, and ceiling effects were 27.66% (short form) and 26.38% (full item bank). CONCLUSIONS: The Applied Cognition outpatient short form demonstrated acceptable psychometric properties and provides a bridge to item response theory-based measurement for settings where point-of-care computing is not available. PMID- 26135370 TI - Osteomalacia as a Cause of Chronic Low Back and Buttock Pain. PMID- 26135371 TI - Sleep Transcutaneous vs. End-Tidal CO2 Monitoring for Patients with Neuromuscular Disease. AB - OBJECTIVE: This study compared transcutaneous carbon dioxide partial pressure (PtcCO2) and end-tidal carbon dioxide partial pressure (PetCO2) monitoring during sleep for patients with neuromuscular disease. DESIGN: This is a retrospective study of patients whose PtcCO2 and PetCO2 were monitored before they began using noninvasive mechanical ventilation. The outcomes were divided into four groupings: group 1, both PtcCO2 and PetCO2 are greater than or equal to 49 mm Hg; group 2, PtcCO2 is greater than or equal to 49 mm Hg but PetCO2 is less than 49 mm Hg; group 3, PtcCO2 is less than 49 mm Hg but PetCO2 is greater than or equal to 49 mm Hg; and group 4, both PtcCO2 and PetCO2 are less than 49 mm Hg. RESULTS: A total of 39 subjects (mean [SD] age, 27.7 [19.3] yrs) were enrolled. PtcCO2 values were significantly higher than PetCO2 values (P < 0.001). The intraclass correlation coefficient between maximal and mean values of PtcCO2 and PetCO2 was 0.612 and 0.718, respectively. Bias and limits of agreement between PtcCO2 and PetCO2 were -7.5 mm Hg and -21.3 to 6.3 mm Hg for maximal values and -4.8 mm Hg and -14.8 to 5.3 mm Hg for mean values. Group 2 included 19 (48.7%) and group 3 included 3 (7.6%) patients who showed discrepancy of hypercapnia between two methods. CONCLUSIONS: Maximum PtcCO2 was significantly greater than maximum PetCO2 for both groups and, therefore, tends to be higher than PetCO2 in this population. This should be taken into consideration when assessing patients for sleep hypoventilation. PMID- 26135372 TI - Effects of Combined Resistive Underwater Exercises and Interferential Current Therapy in Patients with Juvenile Idiopathic Arthritis: A Randomized Controlled Trial. AB - OBJECTIVE: The objective of this study was to verify the effects of combined resistive underwater exercises and interferential current on the peak torque of the quadriceps and hamstrings and pain levels in patients with juvenile idiopathic arthritis. DESIGN: This is a randomized controlled study; 30 children with polyarticular juvenile idiopathic arthritis were randomly distributed into two groups: the control group (n = 15) received the traditional physical therapy program and the study group (n = 15) received resistive underwater exercises and interferential current therapy. Peak torque of the quadriceps and hamstrings and pain levels were evaluated before treatment, 1 mo later, and after 3 mos using the HUMAC NORM, CSMI Testing and Rehabilitation Isokinetic System and visual analog scale, respectively. RESULTS: In the control group, all measures showed significant differences (P < 0.05) after 1 mo except peak torque of left quadriceps and pain levels, and significant differences were found after 3 mos (P < 0.05) in all. In the study group, all measures showed significant differences after 1 and 3 mos (P < 0.05) and there were significant differences between groups after 1 and 3 mos in favor of the study group (P < 0.05). CONCLUSION: The combination of resistive underwater exercises and interferential current therapy is a potentially valuable treatment for patients with juvenile idiopathic arthritis. PMID- 26135373 TI - Quadriceps Fat Pad Impingement and Synovial Hypertrophy with Mild to Moderate Lipoma Arborescens. PMID- 26135374 TI - Sonographic tracking of the upper limb peripheral nerves: a pictorial essay and video demonstration. AB - Ultrasound has been the most useful imaging tool for musculoskeletal disorders whereby peripheral nerve lesions constitute a substantial portion. High resolution ultrasound enables elaboration of peripheral nerve morphology and reciprocal anatomy. However, limited literature is available for delineating standard positions and tracking skills. The present article incorporates a series of ultrasound images and videos to demonstrate how to scan the suprascapular, axillary, musculocutaneous, median, ulnar, and radial nerves. Overall, the authors aim to demonstrate the relevant nerve tracking techniques as regards the upper extremity. PMID- 26135375 TI - Effectiveness of Shoe Stiffening Inserts for First Metatarsophalangeal Joint Osteoarthritis: A Proof-of-Concept Study. AB - OBJECTIVE: The objective of this study was to determine the feasibility of shoe stiffening inserts to reduce pain in first metatarsophalangeal joint osteoarthritis. DESIGN: Thirty-one participants with first metatarsophalangeal joint osteoarthritis were prescribed shoe stiffening inserts and were evaluated at baseline and at 1 and 3 mos. The primary outcome measure was foot pain, assessed using the foot pain domain of the Foot Health Status Questionnaire (possible score ranges from 0 to 100). Secondary outcome measures included foot related disability (foot function domain of the Foot Health Status Questionnaire), self-reported treatment effectiveness, use of rescue medication and other co-interventions, and adverse events. RESULTS: At 1 and 3 mos, statistically significant improvements in foot pain and foot-related disability were observed (mean difference at 3 mos: foot pain = 18.8, 95% confidence interval, 13.3-24.3; foot function = 11.8, 95% confidence interval, 4.3-17.3). Treatment was reported to be effective by 78% of participants. Few participants (4%) reported using pain-relieving medication. Minor adverse events were reported by 30% of participants. CONCLUSIONS: Full-length shoe stiffening inserts may be an effective intervention in first metatarsophalangeal joint osteoarthritis. However, further controlled studies are required. PMID- 26135376 TI - Effects of Tai Chi and Multimodal Exercise Training on Movement and Balance Function in Mild to Moderate Idiopathic Parkinson Disease. AB - OBJECTIVE: The primary aim of this study was to investigate the effects of two different patterns of rehabilitation training on movement and balance function in patients with idiopathic Parkinson disease. DESIGN: Forty patients with Parkinson disease were randomized into the tai chi group (n = 20) or the multimodal exercise training group (n = 20). Outcome measures were assessed at baseline and after 12 wks of exercise. Balance was assessed using the Berg Balance Scale, and movement was assessed by the Unified Parkinson's Disease Rating Scale-Motor Examination, stride length, gait velocity, and Timed Up and Go Test. RESULTS: The multimodal exercise training group improved significantly in movement from baseline, and a reduction in balance impairment was observed for the multimodal exercise training group. The questionnaire results after training showed that the multimodal exercise training is easy to learn and adhere to. No major adverse events were noted in both groups. CONCLUSIONS: This multimodal exercise training could improve motion function and benefit balance function in patients with Parkinson disease. The multimodal exercise training is easy to learn and practice. PMID- 26135377 TI - Cardiopulmonary resuscitation interface adapted for postextubation continuous noninvasive ventilatory support. AB - The authors report that a new oral interface designed for cardiopulmonary resuscitation and use during anesthesia permitted the successful extubation of an "unweanable" 27-yr-old woman with nemaline rod myopathy to continuous noninvasive ventilatory support. She had failed two previous extubation attempts. Tracheotomy and institutional care were avoided as a result. PMID- 26135378 TI - Long-Term Functioning of Patients with Aneurysmal Subarachnoid Hemorrhage: A 4-yr Follow-up Study. AB - OBJECTIVES: The aim was to study changes over time for multiple outcomes based on the International Classification of Functioning, Disability, and Health in patients with aneurysmal subarachnoid hemorrhage and to compare long-term outcomes with norms. DESIGN: A prospective cohort study with 4-yr follow-up was conducted. Main outcome measures were as follows: Center for Epidemiologic Studies-Depression Scale, Fatigue Severity Scale, Trail Making Test A and B, Barthel Index, Sickness Impact Profile-68, Impact on Participation and Autonomy Questionnaire, Social Support List-12, Multidimensional Health Locus of Control Scales, COOP-WONCA Charts, and Short Form-36 Health Survey. RESULTS: Seventy-six patients with aneurysmal subarachnoid hemorrhage were included. Measurements were done at T1 = 0.4 yrs (SD, 0.3 yrs) and T2 = 3.9 yrs (SD, 0.7 yrs) after onset. Significant improvements over time were found for Barthel Index (T1 = 18.5; T2 = 19.5; P = 0.023), Trail Making Test B (T1 = 119.4; T2 = 104.6; P = 0.025), Social Support List-12 total score (T1 = 31.1; T2 = 32.7; P = 0.042) and esteem support (T1 = 10.2; T2 = 10.9; P = 0.027), Multidimensional Health Locus of Control Scales (physician-orientation) (T1 = 21.8; T2 = 19.2; P = 0.020), and Short Form 36 Health Survey (role-emotional) (T1 = 54.6; T2 = 73.9; P = 0.048). Center for Epidemiologic Studies-Depression Scale, Fatigue Severity Scale, Sickness Impact Profile-68, and Short Form-36 Health Survey scores remained stable over time. A decline was found for COOP-WONCA (overall-health) (T1 = 2.3; T2 = 2.7; P = 0.021). At 4-yr follow-up, proportions of depression (27%) and fatigue (60%) were larger and scores on the Fatigue Severity Scale (mean [SE], 4.3 [0.2]), Trail Making Test A (mean [SE], 51.3 [3.9]), and Trail Making Test B (mean [SE], 104.4 [0.2]) were significantly worse than norm scores. CONCLUSIONS: Many patients with aneurysmal subarachnoid hemorrhage had fairly good long-term outcomes, but problems in executive functioning, mood, and fatigue still exist at long-term follow-up. PMID- 26135379 TI - Comorbidities and Behavioral Involvement in the Rehabilitation of Patients with Amputation on Chronic Dialysis. PMID- 26135380 TI - Adipokines enhance oleic acid-induced proliferation of vascular smooth muscle cells by inducing CD36 expression. AB - Adipose tissue is not only releasing lipids but also various adipokines that are both dysregulated in the obese state and may contribute to obesity-associated vascular dysfunction and cardiovascular risk. We have previously shown that the combination of adipocyte-conditioned medium (CM) and oleic acid (OA) increases proliferation of human vascular smooth muscle cells (VSMC) in a synergistic way. We identified vascular endothelial growth factor (VEGF) as a component within CM that is responsible for most of the observed effects. In this study, we investigate novel mechanisms that underlie the combined effects of adipokine and oleic acid-induced proliferation of VSMC. Oleic acid leads to significant lipid accumulation in VSMC that is further enhanced by the combined treatment with CM. Accordingly CM stimulates CD36 expression in VSMC while OA is not affecting CD36. Silencing of CD36 was established and prevents lipid accumulation in all tested conditions. CD36 silencing also abrogates CM- and OA-induced proliferation and considerably reduces proliferation induced by the combination of CM and OA. At the same time, VEGF secretion and VEGF-receptor 1 (VEGF-R1) by VSMC was not affected by CD36 silencing. However, VEGF was not able to induce any proliferation in VSMC after CD36 silencing that also blunted VEGF-induced extracellular signal-regulated kinase (ERK) activation. Finally, combined silencing of CD36 together with a blocking antibody against VEGF prevented most of CMOA-induced proliferation. In conclusion, our results demonstrate that CD36 is mediating CM-induced proliferation of VSMC. Induction of CD36 by adipokines enhances the response of VSMC towards VEGF and OA. PMID- 26135381 TI - Ru-assisted synthesis of Pd/Ru nanodendrites with high activity for ethanol electrooxidation. AB - Due to the specific physical and chemical properties of a highly branched noble metal, the controllable synthesis has attracted much attention. This article reports the synthesis of Pd/Ru nanodendrites by a facile method using an oil bath in the presence of polyvinyl pyrrolidone, potassium bromide and ascorbic acid. The morphology, structure, and composition of the as-prepared catalysts were characterized by means of X-ray diffraction, X-ray photoelectron spectroscopy and transmission electron microscopy. In the electrochemical measurement, the as prepared Pd7/Ru1 bimetallic nanodendrites provide a large electrochemically active surface area and exhibit high peak current density in the forward scan toward ethanol electrooxidation, which is nearly four times higher than those of a pure Pd catalyst. The as-prepared Pd7/Ru1 catalysts also exhibit significantly enhanced cycling stability toward ethanol oxidation in alkaline medium, which are mainly ascribed to the synergetic effect between Pd and Ru. This indicates that the Pd7/Ru1 catalysts should have great potential applications in direct ethanol fuel cells. PMID- 26135382 TI - Is carvedilol better than other beta-blockers for heart failure? AB - There is wide consensus about the benefits of beta-blockers in systolic heart failure. However, it is not clear if one specific beta-blocker is superior to the others. Some guidelines favor three ?evidence-based? beta-blockers (carvedilol, bisoprolol and metoprolol) that have proved to decrease mortality. Carvedilol might have different physiological properties, commonly referred as pleiotropic effects, but the clinical meaning of them is not clear. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including eight pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded there is little or no difference in hospitalization risk between carvedilol and bisoprolol or metoprolol, but carvedilol might decrease mortality compared to metoprolol or bisoprolol. It is uncertain whether nebivolol can be an alternative because the certainty of the evidence is very low. PMID- 26135383 TI - Macroscopic 3D Porous Graphitic Carbon Nitride Monolith for Enhanced Photocatalytic Hydrogen Evolution. AB - A macroscopic 3D porous graphitic carbon nitride (g-CN) monolith is prepared by the one-step thermal polymerization of urea inside the framework of a commercial melamine sponge and exhibits improved photocatalytic water-splitting performance for hydrogen evolution compared to g-CN powder due to the 3D porous interconnected network, larger specific surface area, better visible light capture, and superior charge-separation efficiency. PMID- 26135384 TI - Making large, flowable particles of protein or disaccharide in a mini-scale spray dryer. AB - A mini-scale spray dryer, the ProCept 4M8, with a 1.4 m or 2.1 m drying chamber length has been used to prepare large, flowable particles of catalase, trehalose or lactose. A 25 kHz ultrasonic nozzle or a Rayleigh breakup mono-disperse droplet generator was used for atomization. The ultrasonic nozzle produced dried particles of average diameter >=30 um that show incipient flow behavior when measured with the vibrating spatula method. A high solute concentration of 69% w/w in the liquid feed was required, which is readily achievable with trehalose but not with the viscous catalase solution. At lower solute concentrations, e.g. 20% w/w, the mono-disperse droplet generator was able to produce well flowable particles of approximately 50 um diameter, although with a low yield. This is a result of collisions between the droplets falling through the drying chamber when then coalesce. It is possible to produce dried, flowable particles in milligram quantities on a mini-scale spray dryer such as the ProCept using the 25 kHz ultrasonic nozzle. With the mono-disperse droplet generator the long drying chamber ensures a residence time of a number of seconds, but this also allows droplet coalescence at fall heights >40 cm. PMID- 26135385 TI - Surface functionalizing of a lipid nanosystem to promote brain targeting: step-by step design and physico-chemical characterization. AB - The use of lipid nanosystems as drug delivery to the central nervous system may be advantageous over the current strategies. The aim of this study was to develop and characterize functionalized liposomes for treatment of brain diseases. The covalent method of coupling IgG to liposomes via the derivatized lipid 1,2 dioleoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide](MPB PE) was investigated. Optimized coupling conditions are shown to result in the efficient conjugation of IgG to liposomes containing low concentrations of MPB-PE (3/1 SH:IgG). The qualitative analysis has shown that after the extrusion process, more homogeneous populations of vesicles have been obtained with a nanometric size suitable to be effective to further anchor the protein. Negative values of zeta potential demonstrate that they are stable systems. Lyophilization was used to maintain the stability of the formulation. These very interesting results encourage further investigations to formulate peptide- and protein-loaded immunoliposomes, making targeting of liposomes as an attractive approach for brain drug delivery. PMID- 26135386 TI - Hippocampus and medial striatum dissociation during goal navigation by geometry or features in the domestic chick: An immediate early gene study. AB - We employed a standard reference memory task to study the involvement of the hippocampal formation (HF) of domestic chicks that used the boundary geometry of a test environment to orient to and locate a reward. Using the immediate early gene product c-Fos as a neuronal activity marker, we found enhanced HF activation in chicks that learned to locate rewarded corners using the shape of a rectangular arena compared to chicks trained to solve the task by discriminating local features in a square-shaped arena. We also analyzed neuronal activity in the medial part of the medial striatum (mMSt). Surprisingly, in mMSt we observed a reverse pattern, with higher activity in the chicks that were trained to locate the goal by local features. Our results identify two seemingly parallel, memory systems in chicks, with HF central to the processing of spatial-geometrical information and mMSt important in supporting local feature discrimination. PMID- 26135387 TI - Gender Differences in Academic Achievement: Is Writing an Exception to the Gender Similarities Hypothesis? AB - The gender similarities hypothesis by J. S. Hyde ( 2005 ), based on large-scale reviews of studies, concludes that boys and girls are more alike than different on most psychological variables, including academic skills such as reading and math (J. S. Hyde, 2005 ). Writing is an academic skill that may be an exception. The authors investigated gender differences in academic achievement using a large, nationally stratified sample of children and adolescents ranging from ages 7-19 years (N = 2,027). Achievement data were from the conormed sample for the Kaufman intelligence and achievement tests. Multiple-indicator, multiple-cause, and multigroup mean and covariance structure models were used to test for mean differences. Girls had higher latent reading ability and higher scores on a test of math computation, but the effect sizes were consistent with the gender similarities hypothesis. Conversely, girls scored higher on spelling and written expression, with effect sizes inconsistent with the gender similarities hypothesis. The findings remained the same after controlling for cognitive ability. Girls outperform boys on tasks of writing. PMID- 26135388 TI - Tuberculosis in immigrants in Finland, 1995-2013. AB - Increasing immigration from high tuberculosis (TB) incidence countries is a challenge for surveillance and control in Finland. Here, we describe the epidemiology of TB in immigrants by using national surveillance data. During 1995 2013, 7030 (84.7%) native and 1199 (14.4%) immigrant cases were identified. The proportion of immigrant cases increased from 5.8% in 1995 to 32.1% in 2013, consistent with increasing immigrant population (2.1-5.6%) and decreasing incidence of TB in the native population (from 12.1 to 3.5/100 000). TB cases in immigrants were significantly younger, more often female, and had extrapulmonary TB more often than native cases (P < 0.01 for all comparisons); multidrug resistance was also more common in immigrants than natives (P < 0.01). Immigrant cases were born in 82 different countries; most commonly in Somalia and the former Soviet Union/Russia. During 2008-2013, 433 Mycobacterium tuberculosis isolates from immigrants were submitted for spoligotyping; 10 different clades were identified. Clades were similar to those found in the case's country of birth. Screening immigrants from high-incidence countries and raising awareness of common characteristics and symptoms of TB is important to ensure early diagnosis and to prevent transmission. PMID- 26135389 TI - Biobased Epoxy Nanocomposites Derived from Lignin-Based Monomers. AB - Biobased epoxy nanocomposites were synthesized based on 2-methoxy-4-propylphenol (dihydroeugenol, DHE), a molecule that has been obtained from the lignin component of biomass. To increase the content of hydroxyl groups, DHE was o demethylated using aqueous HBr to yield propylcatechol (DHEO), which was subsequently glycidylated to epoxy monomer. Optimal conditions in terms of yield and epoxy equivalent weight were found to be 60 degrees C with equal NaOH/phenolic hydroxyl molar ratio. The structural evolution from DHE to cured epoxy was followed by (1)H NMR and Fourier transform infrared spectroscopy. The nano-montmorillonite modified DHEO epoxy exhibited improved storage modulus and thermal stability as determined from dynamic mechanical analysis and thermogravimetric analysis. This study widens the synthesis routes of biobased epoxy thermosets from lignin-based molecules. PMID- 26135390 TI - The [2 + 2] Cycloaddition-Retroelectrocyclization and [4 + 2] Hetero-Diels-Alder Reactions of 2-(Dicyanomethylene)indan-1,3-dione with Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity. AB - The reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich alkynes provides two classes of push-pull chromophores with interesting optoelectronic properties. The formal [2 + 2] cycloaddition retroelectrocyclization reaction at the exocyclic double bond of DCID gives cyanobuta-1,3-dienes, and the formal [4 + 2] hetero-Diels-Alder (HDA) reaction at an enone moiety of DCID generates fused 4H-pyran heterocycles. Both products can be obtained in good yield and excellent selectivity by carefully tuning the reaction conditions; in particular, the use of Lewis acids dramatically enhances formation of the HDA adduct. PMID- 26135391 TI - "Married with children" the influence of significant others in TTO exercises. AB - BACKGROUND: Which responder characteristics influence TTO scores remains underexplored. More research is needed in order to understand (differences in) TTO scores, but also in the context of generating representative health state valuations for some population. Previous studies have found age, gender, marital status and subjective life expectancy to influence the number of years traded off. OBJECTIVE: This study aimed to investigate which other responder characteristics influence TTO responses, with an emphasis on consideration of significant others, such as partners and children. METHODS AND DESIGN: We performed a web-based survey in a representative sample of the Dutch general public (aged 18-65). Data on demographics, health status and expectations about future length and quality of life were gathered. Respondents valued three distinct health states using TTO. RESULTS: A total of 1067 respondents completed the questionnaire. Sixty percent of respondents had children and 49 % were married. The mean number of years traded off increased with severity of health states. Higher age and living together were positively associated with number of years traded off. Increases in subjective life expectancy, having children and being male (were negatively associated with the number of years traded-off. CONCLUSION: Age, gender and subjective life expectancy, living together and having children were significantly associated with TTO responses. Consideration of significant others in TTO exercises thus may be important in understanding (differences in) TTO responses and when drawing representative samples from the general public. PMID- 26135392 TI - Tandem copper (Cu) catalysed N-arylation-vinylogous nitroaldol condensation of 3,5-disubstituted 4-nitropyrazoles. AB - A tandem process involving copper catalysed N-arylation and vinylogous nitroaldol condensation is described. The reaction of 3,5-dialkyl substituted 4 nitropyrazoles and ortho-halo substituted (hetero)aryl aldehydes or ketones furnished 3-nitropyrazolo[1,5-a]quinoline and heteroaryl-fused 3 nitropyrazolo[1,5-a]pyridine derivatives in moderate to high yields. PMID- 26135393 TI - Descriptive peer norms, self-control and dietary behaviour in young adults. AB - There is evidence that perceived peer eating norms can influence dietary behaviour. This cross-sectional study examined whether certain personality traits increase the likelihood that personal eating habits are similar to perceived peer eating habits. We assessed frequency of consumption of sugar-sweetened soda (SSS) and sweet pastries (SP), as well as perceived peer descriptive eating norms for SSS and SP in a group of 1056 young adults. We examined whether individual differences in the need for social acceptance and self-control moderated whether participants were likely to display similar dietary habits to their peers. Perceived peer eating norms for SSS and SP predicted frequency of consumption; believing that one's peers frequently consumed SSS and SP was associated with increased personal consumption for both. Individuals with low self-control, as opposed to high self-control, were more likely to adhere to peer norms for SP, but not for SSS. Trait social acceptance needs did not significantly moderate similarity between peer norms and personal consumption for either SSS or SP. The extent to which young adults adhere to descriptive peer dietary norms may depend upon self-control, whereby individuals with low self-control are less able to inhibit social influence of descriptive peer norms on dietary behaviour. PMID- 26135394 TI - Endolog technique for correction of hallux valgus: a prospective study of 30 patients with 4-year follow-up. AB - BACKGROUND: Hallux valgus (HV) is a complex deformity of the forefoot altering the kinematics of walking. Many different treatment alternatives exist for the correction of hallux valgus, but to date, none has been shown to be more effective than any other. The rate of complications following hallux valgus surgery is variable and has been reported as ranging from 1 to 55 % in the scientific literature. The purpose of this preliminary prospective study was to evaluate the result of the Endolog device, an innovative titanium endomedullary nail, for the treatment of HV. METHODS: Thirty patients with mild-to-severe HV were treated with the Endolog device. Clinical evaluation was assessed preoperatively, as well as at 3, 6, 12, 24, and 48 months after surgery with a final follow-up at 4 years, using the American Orthopaedic Foot and Ankle Society (AOFAS) hallux grading system. Computer-assisted measurement of weight-bearing antero-posterior radiographs was taken preoperatively and postoperatively, as well as at 3, 6, 12, 24, and 48 months after surgery. Non-weight-bearing radiographs were taken before the patients were discharged. The radiological parameters measured included the intermetatarsal angle (IMA), the hallux valgus angle (HVA), the distal metatarsal articular angle (DMAA), and the tibial sesamoid position. Statistical analysis was carried out using the paired t test (p < 0.05). RESULTS: The mean AOFAS score was 93.98 points at the 48-month follow up. The postoperative radiographic assessments showed a statistically significant improvement compared with preoperative values. The mean corrections for each angular value at the last follow-up were as follows: IMA 5.95 degrees ; HVA 16.81 degrees ; DMAA 10.70 degrees ; and tibial sesamoid 1.36 degrees . CONCLUSION: The Endolog is a safe and effective technique for the correction of HV deformity, to relieve pain and to preserve joint movement. PMID- 26135395 TI - Task shifting of HIV/AIDS case management to Community Health Service Centers in urban China: a qualitative policy analysis. AB - BACKGROUND: The growing number of people living with HIV/AIDS (PLWHA) in China points to an increased need for case management services of HIV/AIDS. This study sought to explore the challenges and enablers in shifting the HIV/AIDS case management services from Centers for Disease Control and Prevention (CDCs) to Community Health Service Centers (CHSCs) in urban China. METHODS: A qualitative method based on the Health Policy Triangle (HPT) framework was employed to gain in-depth insights into four elements of the task shifting strategy. This included a review on published literature and health policy documents, 15 focus group discussions (FGDs) and 30 in-depth interviews (IDIs) with four types of key actors from three cities in China. A total of 78 studies and 17 policy files at the national, municipal and local levels were obtained and reviewed comprehensively. Three semi-structured interview guides were used to explore key actors' views on shifting the HIV/AIDS case management services to CHSCs. RESULTS: It is necessary and feasible for CHSCs to engage in case management services for PLWHA in local communities. The increasing number of PLWHA and shortage of qualified health professionals in CDCs made shifting case management services downwards to CHSCs an urgent agenda. CHSCs' wide distribution, technical capacity, accessibility and current practice enabled them to carry out case management services for PLWHA. However our findings indicated several challenges in this task shifting process. Those challenges included lack of specific policy and stable financial support for CHSCs, inadequate manpower, relatively low capacity for health service delivery, lack of coordination among sectors, PLWHA's fear for discrimination and privacy disclosure in local communities, which may compromise the effectiveness and sustainability of those services. CONCLUSIONS: Shifting the HIV/AIDS case management services from CDCs to CHSCs is a new approach to cope with the rising number of PLWHA in China, but it should be implemented alongside with other efforts and resources such as increasing public funding, planned team building, professional training, coordination with other sectors and education on privacy protection as well as non-discrimination to make this approach more effective and sustainable. Policy makers need to ensure both political feasibility and resources accessibility to facilitate this shifting process. PMID- 26135396 TI - Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam. AB - The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water sources, including surface water, groundwater and piped water (164 water samples) were systematically screened for antibiotic residues. To better understand antibiotic fate under tropical conditions, the dissipation behavior of selected antibiotics in the aquatic environment was investigated for the first time in mesocosm experiments. None of the investigated antibiotics were detected in groundwater and piped water samples. Surface water, which is still often used for drinking and domestic purposes by local populations, contained median concentrations of 21 ng L-1 sulfamethoxazole (SMX), 4 ng L-1 sulfadiazine (SDZ), 17 ng L-1 trimethoprim (TRIM), and 12 ng L-1 enrofloxacin (ENRO). These concentrations were lower than the predicted no effect concentrations (PNECs) and minimum inhibitory concentrations (MICs), suggesting limited antibiotic-related risk to aquatic ecosystems in the monitored systems. The dissipation half-lives of the studied antibiotics ranged from <1 to 44 days, depending on the availability of sunlight and sediment. Among the studied antibiotics TRIM was the most persistent in water systems. TRIM was not susceptible to photodegradation, while the dissipation of ENRO and SDZ was influenced by photolysis. The recorded dissipation models gave good predictions of the occurrence and concentrations of TRIM, ENRO and SDZ in surface water. In summary, the currently measured concentrations of the investigated antibiotics are unlikely to cause immediate risks to the aquatic environment, yet the persistence of these antibiotics is of concern and might lead to chronic exposure of aquatic organisms as well as humans. PMID- 26135397 TI - New insights into the immunopathology of early Toxocara canis infection in mice. AB - BACKGROUND: Nematodes of the genus Toxocara are cosmopolitan roundworms frequently found in dogs and cats. Toxocara spp. can accidentally infect humans and cause a zoonosis called human toxocariasis, which is characterized by visceral, ocular or cerebral migration of larval stages of the parasite, without completing its life cycle. In general, chronic nematode infections induce a polarized TH2 immune response. However, during the initial phase of infection, a strong pro-inflammatory response is part of the immunological profile and might determine the outcome and/or pathology of the infection. METHODS: Parasitological aspects and histopathology during larval migration were evaluated after early T. canis experimental infection of BALB/c mice, which were inoculated via the intra gastric route with a single dose of 1000 fully embryonated eggs. Innate immune responses and systemic cytokine patterns (TH1, TH2, TH17 and regulatory cytokines) were determined at different times after experimental challenge by sandwich ELISA. RESULTS: We found that experimental infection with T. canis induced a mix of innate inflammatory/TH17/TH2 responses during early infection, with a predominance of the latter. The TH2 response was evidenced by significant increases in cytokines such as IL-4, IL-5, IL-13 and IL-33, in addition to increasing levels of IL-6 and IL-17. No significant increases were observed for IL-10, TNF-alpha or IFN-gamma levels. In parallel, parasitological analysis clearly revealed the pattern of larval migration through the mouse organs, starting from the liver in the first 24 h of infection, reaching the peak in the lungs on the 3rd day of infection and finally being found numerously in the brain after 5 days of infection. Peripheral leukocytosis, characterized by early neutrophilia and subsequent eosinophilia, was remarkable during early infection. The tissue damage induced by larvae was evidenced by histopathological analysis of the organs at different time points of infection. In all of the affected organs, larval migration induced intense inflammatory infiltrate and hemorrhage. CONCLUSION: In conclusion, these new insights into early T. canis infection in mice presented here enabled a better understanding of the immunopathological events that might also occur during human toxocariasis, thus contributing to future strategies of diagnosis and control. PMID- 26135400 TI - Fracking Cannot Be Reconciled with Climate Change Mitigation Policies. PMID- 26135398 TI - Co-Expression of Ezrin-CLIC5-Podocalyxin Is Associated with Migration and Invasiveness in Hepatocellular Carcinoma. AB - BACKGROUND AND AIM: Prognostic markers are important for predicting the progression and staging of hepatocellular carcinoma (HCC). Ezrin (EZR) and Podocalyxin (PODXL) are proteins associated with invasion, migration and poor prognosis in various types of cancer. Recently, it has been observed that chloride intracellular channel 5 (CLIC5) forms a complex with EZR and PODXL and that it is required for podocyte structure and function. In this study, we evaluated the overexpression of EZR, PODXL and CLIC5 in HCC. METHODS: The modified resistant hepatocyte model (MRHR), human biopsies and HCC cell lines (HepG2, Huh7 and SNU387) were used in this study. Gene and protein expression levels were evaluated in the MRHR by qRT-PCR, Western blot and immunohistochemistry analyses, and protein expression in the human biopsies was evaluated by immunohistochemistry. Protein expression in the HCC cell lines was evaluated by immunofluorescence and Western blot, also the migration and invasive abilities of Huh7 cells were evaluated using shRNA-mediated inhibition. RESULTS: Our results indicated that these genes and proteins were overexpressed in HCC. Moreover, when the expression of CLIC5 and PODXL was inhibited in Huh7 cells, we observed decreased migration and invasion. CONCLUSION: This study suggested that EZR, CLIC5 and PODXL could be biological markers to predict the prognosis of HCC and that these proteins participate in migration and invasion processes. PMID- 26135399 TI - Neuroimaging Analysis of the Dopamine Basis for Apathetic Behaviors in an MPTP Lesioned Primate Model. AB - Apathy commonly occurs in Parkinson disease (PD) patients; however, the role of dopamine in the pathophysiology of apathy remains elusive. We previously demonstrated that dopaminergic dysfunction within the ventral tegmental area (VTA)-nucleus accumbens (NAcc) pathway contributes to the manifestation of apathetic behaviors in monkeys treated with the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now extend these studies to identify dopaminergic dysfunction in cortical regions that correlate with development of apathetic behaviors. Specifically, we measured the effects of MPTP on monkeys' willingness to attempt goal directed behaviors, which is distinct from their ability to perform tasks. A total of 16 monkeys had baseline magnetic resonance imaging (MRI) and positron emission tomography (PET), using 6 [18F]fluorodopa (FD), [11C]dihydrotetrabenazine (DTBZ), and 2beta [11C]carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT). The monkeys received unilateral infusion of different doses of MPTP (0 - 0.31mg/kg) to produce a wide range of severity of motor parkinsonism. Eight weeks after MPTP, PET scans were repeated and animals were euthanized. Apathetic behavior and motor impairments were assessed blindly both pre- and post-MPTP infusion. Apathy scores were compared to in vitro and in vivo dopaminergic measures. Apathy scores increased following MPTP and correlated with PET measures of dopaminergic terminals (DTBZ or CFT) in dorsal lateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (VMPFC), and insular cortex (IC). Among all the cortical regions assessed, forward step-wise regression analyses indicated that only stereologic cell counts in VTA, and not counts in the substantia nigra (SN), predict dopamine transporter changes in IC. Our findings suggest that dopaminergic dysfunction within the VTA IC pathway plays a role in the manifestation of apathetic behaviors in MPTP lesioned primates. PMID- 26135401 TI - HHT and gastric telangiectasia. PMID- 26135403 TI - On the inclusion of post-MP2 contributions to double-hybrid density functionals. AB - In this study, we explore the effect of supplementing the DuT spin-component scaled double-hybrid density functional method with post-second-order Moller Plesset-type theory (MP2) correlation terms. We find that the inclusion of additional MP3 correlation energies has almost no effect on the performance. Further addition of correlation effects from MP4 generally leads to a small improvement in the performance. However, we find that the inclusion of the higher order perturbative correlation effects does not rectify some major shortcomings of DuT for more challenging systems, and the use of MP4, in fact, leads to a significant deterioration in the performance in some cases. We also find that the use of correlation energies from CCSD(T) instead of those from MP3 and MP4 does not lead to a substantial improvement over the MP4-based method, both in general and in some difficult cases that we have examined. An additional observation is that, for large systems that are dominated by noncovalent interactions, DuT and the two MPn-based post-MP2 double-hybrid density functional theory (DFT) procedures all benefit from the inclusion of dispersion corrections. Overall, our investigation suggests that the current generation of MP2-based double-hybrid DFT methods may already be providing close to the optimal performance that can be achieved with the double-hybrid methodology paired with spin-component-scaling. Development of even better double hybrids is an active research field, and we hope that our study provides valuable insights. We recommend the continuing use of existing MP2-based double-hybrid methods as a bridging level between hybrid density functional procedures and high-level wave-function-based procedures. PMID- 26135402 TI - Acceptability of a theory-based sedentary behaviour reduction intervention for older adults ('On Your Feet to Earn Your Seat'). AB - BACKGROUND: Adults aged 60 years and over spend most time sedentary and are the least physically active of all age groups. This early-phase study explored acceptability of a theory-based intervention to reduce sitting time and increase activity in older adults, as part of the intervention development process. METHODS: An 8-week uncontrolled trial was run among two independent samples of UK adults aged 60-75 years. Sample 1, recruited from sheltered housing on the assumption that they were sedentary and insufficiently active, participated between December 2013 and March 2014. Sample 2, recruited through community and faith centres and a newsletter, on the basis of self-reported inactivity (<150 weekly minutes of moderate-to-vigorous activity) and sedentary behaviour (>= 6 h mean daily sitting), participated between March and August 2014. Participants received a booklet offering 16 tips for displacing sitting with light-intensity activity and forming activity habits, and self-monitoring 'tick-sheets'. At baseline, 4-week, and 8-week follow-ups, quantitative measures were taken of physical activity, sedentary behaviour, and habit. At 8 weeks, tick-sheets were collected and a semi-structured interview conducted. Acceptability was assessed for each sample separately, through attrition and adherence to tips, ANOVAs for behaviour and habit changes, and, for both samples combined, thematic analysis of interviews. RESULTS: In Sample 1, 12 of 16 intervention recipients completed the study (25% attrition), mean adherence was 40% (per-tip range: 15-61%), and there were no clear patterns of changes in sedentary or physical activity behaviour or habit. In Sample 2, 23 of 27 intervention recipients completed (15% attrition), and mean adherence was 58% (per-tip range: 39-82%). Sample 2 decreased mean sitting time and sitting habit, and increased walking, moderate activity, and activity habit. Qualitative data indicated that both samples viewed the intervention positively, found the tips easy to follow, and reported health and wellbeing gains. CONCLUSIONS: Low attrition, moderate adherence, and favourability in both samples, and positive changes in Sample 2, indicate the intervention was acceptable. Higher attrition, lower adherence, and no apparent behavioural impact among Sample 1 could perhaps be attributable to seasonal influences. The intervention has been refined to address emergent acceptability problems. An exploratory controlled trial is underway. PMID- 26135404 TI - Changes in Acceptance in a Low-Intensity, Group-Based Acceptance and Commitment Therapy (ACT) Chronic Pain Intervention. AB - BACKGROUND: Acceptance and commitment therapy has shown to be effective in chronic pain rehabilitation, and acceptance has been shown to be a key process of change. The influence of treatment dose on acceptance is not clear, and in particular, the effectiveness of a non-intensive treatment (<20 h) in a tertiary pain clinic is required. PURPOSE: The purpose of the study was to assess the effectiveness of a low-intensity, acceptance and commitment therapy (ACT) group program for chronic pain. The study sought to compare, at both groups and individual patient levels, changes in acceptance with changes observed in previous ACT studies. METHODS: Seventy-one individuals with chronic pain commenced a 9-week ACT-based group program at an outpatient chronic pain service. In addition to acceptance, outcomes included the following: pain catastrophizing, depression, anxiety, quality of life, and pain-related anxiety. To compare the current findings with previous research, effect sizes from seven studies were aggregated using the random-effects model to calculate benchmarks. Reliable change indices (RCIs) were applied to assess change on an individual patient level. RESULTS: The ACT intervention achieved a statistically significant increase in acceptance and medium effect size (d = 0.54) at a group level. Change in acceptance was of a similar magnitude to that found in previous ACT studies that examined interventions with similar treatment hours (<20 h). Results across other outcome measures demonstrated small to medium effect sizes (d = 0.01 to 0.48, mean = 0.26). Reliable improvement in acceptance occurred in approximately one-third (37.2, 90% CI) of patients. Approximately three-quarters (74.3, 90% CI) demonstrated reliable change in at least one of the outcome measures. CONCLUSIONS: The low-intensity, group-based ACT intervention was effective at a group level and showed a similar magnitude of change in acceptance to previous ACT studies employing low-intensity interventions. Three-quarters of patients reported reliable change on at least one outcome measure. PMID- 26135405 TI - Impact of I30T and I30M substitution in MPZ gene associated with Dejerine-Sottas syndrome type B (DSSB): A molecular modeling and dynamics. AB - Myelin protein zero (MPZ) gene encodes MPZ protein is a vital component of the myelin sheath. Mutationsassociated with MPZ gene leads to severe de hypomyelination Dejerine-Sottas syndrome type B (DSSB) also termed as Charcot Marie-Tooth disease (CMT) type 3. In this work, we employed a set of various in silico prediction methods to screen 97 nsSNPs associated with MPZ gene. Based on this, we identified the nsSNPs to be most deleterious and pathogenic associated with DSSB. To get more insight into the mutational effect at three-dimensional structural level, we modeled the homology structure of native type as well as I30T and I30M mutant of MPZ protein using Modeler 9.13 software. Molecular dynamics simulation was initiated to explain the impact of the mutation on its structure and function. The obtained results depict that the protein with I30T mutation had variable structural conformation and dynamic behavior than native and mutant I30M of MPZ protein. We hope our computational insight might be helpful in rationalizing the deleterious mutations in DSSB and the advancement of novel pharmacological strategy. PMID- 26135406 TI - Conformity biased transmission in social networks. AB - In this paper we explore how the structure of a population can differentially influence the spread of novel behaviors, depending on the learning strategy of each individual. We use a series of simulations to analyze how frequency dependent learning rules might affect how easily novel behaviors can spread through a population on four artificial social networks, and three real social networks. We measured the likelihood that a novel behavior could spread through the population, and the likelihood that there were multiple behavioral variants in the population, a measure of cultural diversity. Surprisingly, we find few differences between networks on either measure. However, we do find that where a behavior originated on a network can have a substantial impact on the likelihood that it spreads, and that this location effect depends on the learning strategy of an individual. These results suggest that for first-order analysis of how behaviors spread through a population, social network structure can be ignored, but that the social network structure may be useful for more fine-tuned analyses and predictions. PMID- 26135407 TI - Indicator of the Stacking Interaction in the DNA Double-Helical Structure: ChiraSac Study. AB - The double-helical structures of DNA are experimentally distinguished by the circular dichroism (CD) spectra. The CD spectra are quite different between the left- and right-handed double-helical structures of DNA. The lowest peak is negative for the left-handed Z-DNA but positive for the right-handed B-DNA. Using the Z-DNA model with a strong stacking interaction, we examined whether the CD spectra depend on the distance between the two base pairs, deoxy-guanosine (dG) and deoxy-cytidine (dC). The result showed that the feature of the SAC-CI CD spectra changes from Z-DNA to B-DNA when increasing the distance between the two base pairs. Therefore, we concluded that the stacking interaction is the origin of the lowest negative peak, being the feature of the CD spectra of Z-DNA, and at the same time that the lack of the negative peak at about 290-300 nm of the CD spectra of B-DNA is due to the weak stacking interaction in B-DNA. PMID- 26135408 TI - Emerging potential of exosomes and noncoding microRNAs for the treatment of neurological injury/diseases. AB - Recent discoveries of cellular generation of exosomes, small (~ 30 - 100 nm) complex lipid membrane structures which encapsulate and transport proteins, RNAs, including microRNAs (miRNAs) have provided new insight in how cells within organisms communicate. These discoveries will likely have a major impact on the treatment of disease, with cancers and neurological diseases as evident targets. Exosomes provide a major medium of intercellular communications and thereby, there being a potential by altering communications and instructions for protein production, we can employ exosomes to treat diseases. We now have an opportunity to treat neurological disease by modifying intercellular communication networks. Recent work demonstrating that the therapeutic benefit provided by stem cells for the treatments of stroke and traumatic brain injury depend on their generation and release of exosomes provides a foundation for exosome-based therapy. Cell free exosomes have also been recently employed to effectively treat stroke and brain trauma. The content of exosomes, particularly their miRNA cargo which can concurrently impact the post-transcriptional regulation of many genes, can be regulated. We are at the cusp of capitalizing on this important means of intercellular communications for the treatment of diseases, such as cancers and neurological diseases, among many others. PMID- 26135409 TI - Correction: Prenatal Exposure to Maternal Bereavement and Childbirths in the Offspring: A Population-Based Cohort Study. PMID- 26135410 TI - Success in failure. PMID- 26135411 TI - Gene politics. PMID- 26135412 TI - Light detective. PMID- 26135413 TI - Practical policies can combat gender inequality. PMID- 26135425 TI - Super-muscly pigs created by small genetic tweak. PMID- 26135426 TI - How an Oregon cancer institute raised a billion dollars. PMID- 26135427 TI - Plant collections left in the cold by cuts. PMID- 26135428 TI - Researchers pin down risks of low-dose radiation. PMID- 26135430 TI - Corrections. PMID- 26135429 TI - Europe braces for more climate litigation. PMID- 26135431 TI - The hunt for the world's missing carbon. PMID- 26135432 TI - Machine ethics: The robot's dilemma. PMID- 26135433 TI - Reproducibility: Don't cry wolf. PMID- 26135434 TI - Sustainable mobility: Six research routes to steer transport policy. PMID- 26135438 TI - August Weismann: A prescient view of women in evolution. PMID- 26135439 TI - Europe: Animal studies must be useful, says public. PMID- 26135440 TI - Be prepared: Europe needs Ebola outbreak consortium. PMID- 26135441 TI - Species naming: Taxonomic glory easier on eBay? PMID- 26135442 TI - Nanotechnology: Colourful particles for spectrometry. PMID- 26135443 TI - Public health: The case for pay to quit. PMID- 26135444 TI - Planetary science: Sink holes and dust jets on comet 67P. PMID- 26135445 TI - Evolution: Reptile sex determination goes wild. PMID- 26135446 TI - Neurobiology: Inversion in the worm. PMID- 26135447 TI - Self-similar energetics in large clusters of galaxies. AB - Massive galaxy clusters are filled with a hot, turbulent and magnetized intra cluster medium. Still forming under the action of gravitational instability, they grow in mass by accretion of supersonic flows. These flows partially dissipate into heat through a complex network of large-scale shocks, while residual transonic (near-sonic) flows create giant turbulent eddies and cascades. Turbulence heats the intra-cluster medium and also amplifies magnetic energy by way of dynamo action. However, the pattern regulating the transformation of gravitational energy into kinetic, thermal, turbulent and magnetic energies remains unknown. Here we report that the energy components of the intra-cluster medium are ordered according to a permanent hierarchy, in which the ratio of thermal to turbulent to magnetic energy densities remains virtually unaltered throughout the cluster's history, despite evolution of each individual component and the drive towards equipartition of the turbulent dynamo. This result revolves around the approximately constant efficiency of turbulence generation from the gravitational energy that is freed during mass accretion, revealed by our computational model of cosmological structure formation. The permanent character of this hierarchy reflects yet another type of self-similarity in cosmology, while its structure, consistent with current data, encodes information about the efficiency of turbulent heating and dynamo action. PMID- 26135449 TI - A colloidal quantum dot spectrometer. AB - Spectroscopy is carried out in almost every field of science, whenever light interacts with matter. Although sophisticated instruments with impressive performance characteristics are available, much effort continues to be invested in the development of miniaturized, cheap and easy-to-use systems. Current microspectrometer designs mostly use interference filters and interferometric optics that limit their photon efficiency, resolution and spectral range. Here we show that many of these limitations can be overcome by replacing interferometric optics with a two-dimensional absorptive filter array composed of colloidal quantum dots. Instead of measuring different bands of a spectrum individually after introducing temporal or spatial separations with gratings or interference based narrowband filters, a colloidal quantum dot spectrometer measures a light spectrum based on the wavelength multiplexing principle: multiple spectral bands are encoded and detected simultaneously with one filter and one detector, respectively, with the array format allowing the process to be efficiently repeated many times using different filters with different encoding so that sufficient information is obtained to enable computational reconstruction of the target spectrum. We illustrate the performance of such a quantum dot microspectrometer, made from 195 different types of quantum dots with absorption features that cover a spectral range of 300 nanometres, by measuring shifts in spectral peak positions as small as one nanometre. Given this performance, demonstrable avenues for further improvement, the ease with which quantum dots can be processed and integrated, and their numerous finely tuneable bandgaps that cover a broad spectral range, we expect that quantum dot microspectrometers will be useful in applications where minimizing size, weight, cost and complexity of the spectrometer are critical. PMID- 26135448 TI - Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse. AB - Pits have been observed on many cometary nuclei mapped by spacecraft. It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments and models cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts. Alternative mechanisms like explosive activity have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface. PMID- 26135450 TI - A model-tested North Atlantic Oscillation reconstruction for the past millennium. AB - The North Atlantic Oscillation (NAO) is the major source of variability in winter atmospheric circulation in the Northern Hemisphere, with large impacts on temperature, precipitation and storm tracks, and therefore also on strategic sectors such as insurance, renewable energy production, crop yields and water management. Recent developments in dynamical methods offer promise to improve seasonal NAO predictions, but assessing potential predictability on multi-annual timescales requires documentation of past low-frequency variability in the NAO. A recent bi-proxy NAO reconstruction spanning the past millennium suggested that long-lasting positive NAO conditions were established during medieval times, explaining the particularly warm conditions in Europe during this period; however, these conclusions are debated. Here, we present a yearly NAO reconstruction for the past millennium, based on an initial selection of 48 annually resolved proxy records distributed around the Atlantic Ocean and built through an ensemble of multivariate regressions. We validate the approach in six past-millennium climate simulations, and show that our reconstruction outperforms the bi-proxy index. The final reconstruction shows no persistent positive NAO during the medieval period, but suggests that positive phases were dominant during the thirteenth and fourteenth centuries. The reconstruction also reveals that a positive NAO emerges two years after strong volcanic eruptions, consistent with results obtained from models and satellite observations for the Mt Pinatubo eruption in the Philippines. PMID- 26135451 TI - Sex reversal triggers the rapid transition from genetic to temperature-dependent sex. AB - Sex determination in animals is amazingly plastic. Vertebrates display contrasting strategies ranging from complete genetic control of sex (genotypic sex determination) to environmentally determined sex (for example, temperature dependent sex determination). Phylogenetic analyses suggest frequent evolutionary transitions between genotypic and temperature-dependent sex determination in environmentally sensitive lineages, including reptiles. These transitions are thought to involve a genotypic system becoming sensitive to temperature, with sex determined by gene-environment interactions. Most mechanistic models of transitions invoke a role for sex reversal. Sex reversal has not yet been demonstrated in nature for any amniote, although it occurs in fish and rarely in amphibians. Here we make the first report of reptile sex reversal in the wild, in the Australian bearded dragon (Pogona vitticeps), and use sex-reversed animals to experimentally induce a rapid transition from genotypic to temperature-dependent sex determination. Controlled mating of normal males to sex-reversed females produces viable and fertile offspring whose phenotypic sex is determined solely by temperature (temperature-dependent sex determination). The W sex chromosome is eliminated from this lineage in the first generation. The instantaneous creation of a lineage of ZZ temperature-sensitive animals reveals a novel, climate-induced pathway for the rapid transition between genetic and temperature-dependent sex determination, and adds to concern about adaptation to rapid global climate change. PMID- 26135453 TI - Correction. PMID- 26135452 TI - Computers read the fossil record. PMID- 26135456 TI - Surgically managed perinatal testicular torsion: a single centre experience. AB - OBJECTIVE: The objective of this series is to describe the clinical features and immediate outcomes of surgically managed perinatal testicular torsion (PTT). METHODS: A retrospective chart review of the cases of PTT diagnosed in neonates less than 1 month of age was conducted. The cases were identified from the hospital database maintained prospectively over 24 years at the sole tertiary referral centre for the state of Western Australia. RESULTS: Twenty eight cases of PTT were identified, being 23 unilateral and 5 bilateral. All the five bilateral cases were asynchronous and three were identified incidentally on surgical exploration of unilateral torsion. The testis was clinically salvaged in two newborns at the time of follow-up. CONCLUSION: Asynchronous bilateral PTT could be missed on physical examination and identified on surgical exploration of unilateral PTT. Emergency exploration may result in salvage of the contralateral torted testis. PMID- 26135455 TI - Improving antimicrobial prescribing in Irish primary care through electronic data collection and surveillance: a feasibility study. AB - BACKGROUND: The increase in the spread of antimicrobial resistance (AMR) in bacterial pathogens and limited availability of new antimicrobials places immense pressure on general practitioners (GPs) to prescribe appropriately. Currently, electronic antimicrobial prescribing data is not routinely collected from GPs in Ireland for surveillance purposes to assess regional specific fluctuations or trends in antimicrobial prescribing. The current study aimed to address this issue by assessing the feasibility of remotely extracting antimicrobial prescribing data from primary care practices in Ireland, for the purpose of assessing prescribing quality using the European Surveillance of Antimicrobial Consumption (ESAC) drug specific quality indicators. METHODS: Participating practices (n = 30) uploaded data to the Irish Primary Care Research Network (IPCRN). The IPCRN data extraction facility is integrated within the practice patient management software system and permitted the extraction of anonymised patient prescriptions for a one year period, from October 2012 to October 2013. The quality of antimicrobial prescribing was evaluated using the twelve ESAC drug specific quality indicators using the defined daily dose (DDD) per 1,000 inhabitants per day (DID) methodology. National and European prescribing surveillance data (based on total pharmacy sales) was obtained for a comparative analysis. RESULTS: Antimicrobial prescriptions (n = 57,079) for 27,043 patients were obtained from the thirty study practices for a one year period. On average, study practices prescribed a greater proportion of quinolones (37 % increase), in summer compared with winter months, a variation which was not observed in national and European data. In comparison with national data, study practices prescribed higher proportions of beta-lactamase-sensitive penicillins (4.98 % vs. 4.3 %) and a greater use of broad spectrum compared to narrow-spectrum antimicrobials (ratio = 9.98 vs. 6.26) was observed. Study practices exceeded the European mean for prescribing combinations of penicillins, including beta lactamase inhibitors. CONCLUSIONS: This research demonstrates the feasibility and potential use of direct data extraction of anonymised practice data directly through the patient management software system. The data extraction methods described can facilitate the provision of routinely collected data for sustained and inclusive surveillance of antimicrobial prescribing. These comparisons may initiate further improvements in antimicrobial prescribing practices by identifying potential areas for improvement. PMID- 26135457 TI - Maternal physical activity before and during the prenatal period and the offspring's academic performance in youth. The UP&DOWN study. AB - OBJECTIVE: To examine the association of maternal physical activity before and during pregnancy with academic performance in youth. METHODS: This study included 1868 youth (6-18 years) and their mothers. Mothers recalled their physical activity before and during pregnancy. Mothers were categorized into four groups: "remained active", "became inactive", "became active" and "remained inactive". Academic performance was assessed through school records. RESULTS: Boys whose mothers practiced physical activity before or during pregnancy had significantly higher scores in academic performance indicators independently of physical activity, fitness, current body mass index (BMI) and birthweight than those whose mothers did not practice physical activity before or during pregnancy (all p < 0.05). In addition, boys whose mothers remained active had higher scores in all academic indicators (ranging from +0.358 to +0.543) than boys whose mothers remained inactive. Boys whose mothers remained active had higher scores in Language (score +0.546; 95% CI, 0.150-0.940), average of Math and Language (score +0.468; 95% CI, 0.100-0.836) and grade point average (GPA) (score +0.368; 95% CI, 0.092-0.644) than boys whose mothers became active. CONCLUSIONS: Maternal physical activity before and during pregnancy may positively influence youth's academic performance. Continuing maternal physical activity practice during pregnancy may have greater benefits for youth's academic performance. PMID- 26135458 TI - Thrombophilic genes alterations as risk factor for recurrent pregnancy loss. AB - OBJECTIVE: The important polymorphisms leading to inherited thrombophilia are Factor V Leiden (FVL), Prothrombin G20210A and MTHFR C677T and A1298C. The frequencies also the correlation among these polymorphisms and RPL have been reported controversially in various populations. Our clinic is one of the referral centers in reproductive biomedicine in which patients in all over Iran refer to; thus the results of this study could be considered clinically beneficial. Besides, in the present study, not only the frequency of specific but also multiple thrombophilic gene alterations were compared in Iranian women with RPL and a control group. METHODS: The patients group comprised 330 women with three or more consecutive RPLs. The control population included 350 women with at least one child and no history of pregnancy loss. FVL, Prothrombin G20210A and MTHFR C677T polymorphisms were analyzed by Strip assay kit. MTHFR A1298C was genotyped by PCR-RFLP. RESULTS: The frequencies of FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C mutations in patients were 8.48, 4.24, 45.45 and 59.39%, and in controls were 2.86, 2.86, 34.28 and 6%, respectively. CONCLUSIONS: The present data showed that FVL, MTHFR polymorphisms also combined with thrombophilic gene mutations have a strong association with RPL. PMID- 26135460 TI - Erratum: Near-shore Antarctic pH variability has implications for the design of ocean acidification experiments. PMID- 26135459 TI - Unravelling the Evolution of the Allatostatin-Type A, KISS and Galanin Peptide Receptor Gene Families in Bilaterians: Insights from Anopheles Mosquitoes. AB - Allatostatin type A receptors (AST-ARs) are a group of G-protein coupled receptors activated by members of the FGL-amide (AST-A) peptide family that inhibit food intake and development in arthropods. Despite their physiological importance the evolution of the AST-A system is poorly described and relatively few receptors have been isolated and functionally characterised in insects. The present study provides a comprehensive analysis of the origin and comparative evolution of the AST-A system. To determine how evolution and feeding modified the function of AST-AR the duplicate receptors in Anopheles mosquitoes, were characterised. Phylogeny and gene synteny suggested that invertebrate AST-A receptors and peptide genes shared a common evolutionary origin with KISS/GAL receptors and ligands. AST-ARs and KISSR emerged from a common gene ancestor after the divergence of GALRs in the bilaterian genome. In arthropods, the AST-A system evolved through lineage-specific events and the maintenance of two receptors in the flies and mosquitoes (Diptera) was the result of a gene duplication event. Speciation of Anopheles mosquitoes affected receptor gene organisation and characterisation of AST-AR duplicates (GPRALS1 and 2) revealed that in common with other insects, the mosquito receptors were activated by insect AST-A peptides and the iCa2+-signalling pathway was stimulated. GPRALS1 and 2 were expressed mainly in mosquito midgut and ovaries and transcript abundance of both receptors was modified by feeding. A blood meal strongly up regulated expression of both GPRALS in the midgut (p < 0.05) compared to glucose fed females. Based on the results we hypothesise that the AST-A system in insects shared a common origin with the vertebrate KISS system and may also share a common function as an integrator of metabolism and reproduction. HIGHLIGHTS: AST A and KISS/GAL receptors and ligands shared common ancestry prior to the protostome-deuterostome divergence. Phylogeny and gene synteny revealed that AST AR and KISSR emerged after GALR gene divergence. AST-AR genes were present in the hemichordates but were lost from the chordates. In protostomes, AST-ARs persisted and evolved through lineage-specific events and duplicated in the arthropod radiation. Diptera acquired and maintained functionally divergent duplicate AST AR genes. PMID- 26135461 TI - Utility of the SYNTAX score in predicting outcomes after coronary intervention for chronic total occlusion. AB - BACKGROUND: Chronic total occlusion (CTO) lesions are a challenging issue. When dealing with complex CTO lesions in patients undergoing percutaneous coronary intervention (PCI), it is important to evaluate not only the CTO lesion itself but also atherosclerotic lesions of the whole coronary artery tree. The utility of the SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Trial) score in patients with CTO undergoing PCI is unclear. METHODS: This retrospective study included 304 consecutive patients with CTO lesions who underwent PCI. Primary endpoints were procedural failure and major adverse cardiac events (MACE) within 30 days. The SYNTAX and J-CTO (Multicenter CTO Registry in Japan) scores were assessed before the procedures, and patients were divided into two groups according to SYNTAX criteria: high (> 22; n = 158) and low (<= 22; n = 146) SYNTAX scores. RESULTS: Procedural success was achieved in 252 patients (82.9 %). Patients with a high SYNTAX score had significantly lower procedural success than those with a low SYNTAX score (74.7 % versus 91.8 %, p < 0.0001). There were 13 MACE (8.2 %) in patients with high SYNTAX scores and two MACE (1.4 %) in those with low scores. The SYNTAX and J-CTO scores had odds ratios of 3.33 (95 %CI, 1.44-7.74) and 3.64 (95 %CI, 1.24-10.66) for procedural failure. A higher SYNTAX score (> 22) was also an independent predictor of 30-day MACE after PCI (odds ratio = 4.80, 95 %Cl 1.03-22.42). CONCLUSION: The SYNTAX score is predictive of procedural failure, as is the J-CTO score. Furthermore, a higher SYNTAX score is strongly associated with an increased risk of 30-day MACE. The SYNTAX score is useful for clinical decision making when treating patients with complex CTO lesions. PMID- 26135462 TI - Antithrombotic therapy after percutaneous coronary intervention in patients requiring oral anticoagulant treatment. A meta-analysis. AB - AIM: The aim of this meta-analysis was to evaluate the benefits and risks of triple therapy (TT) compared with dual therapy (DT) for patients with an indication for anticoagulation who had undergone percutaneous coronary intervention. BACKGROUND: An increasing number of patients undergoing percutaneous coronary intervention have atrial fibrillation or other indications for oral anticoagulants. For these patients, TT (oral anticoagulants plus aspirin and clopidogrel) is indicated, but this type of treatment increases the risk of bleeding. Thus, it remains controversial whether these patients can benefit more from TT. METHODS: We identified 23 clinical trials that compared TT with DT (aspirin and clopidogrel or oral anticoagulants plus a single antiplatelet drug) after percutaneous coronary intervention in patients undergoing oral anticoagulant (OAC) treatment. The follow-up period ranged from 1 month to 25 months. Two coauthors independently recorded the data on interventions and on the occurrence of major adverse cardiac events (MACE), all-cause death, and major bleeding events. RESULTS: The 23 clinical trials comprised 22,212 participants. Our analysis was feasible because the baseline characteristics and grouping criteria were similar in all groups. The results indicated that TT was more efficacious than DT [dual antiplatelet (DAPT) or OAC + single antiplatelet] in reducing MACE/stroke (RR = 0.76, 95 % CI: 0.70-0.83; p < 0.00001 and RR = 0.67, 95 % CI: 0.59-0.75; p < 0.00001, respectively) There was a significant reduction in all-cause death in the TT regimen compared with the DT regimen (RR = 0.64, 95 % CI: 0.56-0.73; p < 0.00001 and RR = 0.48, 95 % CI: 0.39-0.58; p < 0.00001, respectively). In a subgroup analysis without retrospective studies, we found that there was no significant difference between TT and DT with regard to MACE/stroke (RR = 1.06, 95 % CI: 0.88-1.27; p = 0.54 and RR = 0.95, 95 % CI: 0.79 1.14; p = 0.58, respectively) and all-cause death (RR = 0.84, 95 % CI: 0.63-1.12; p = 0.24 and RR = 1.13, 95 % CI: 0.78-1.64; p = 0.51, respectively). We also found that TT significantly increased the risk of major bleeding compared with DAPT (RR = 1.36; 95 % CI: 1.17-1.58; p < 0.0001). However, there was no difference between TT and OAC + single antiplatelet agent (RR = 0.96; 95 % CI: 0.75-1.21; p = 0.71). Finally, in the comparison between TT and OAC + clopidogrel, there were no differences in major bleeding events, MACE and stroke, and all-cause death. CONCLUSION: Our analysis found no statistically significant difference between TT and DT with regard to all-cause death and MACE/stroke risk. At the same time, the available data demonstrated that TT increased the risk of major bleeding. If the international normalized ratio is in the target range, the risk of bleeding may be lowered. The data from Asian countries were limited, and therefore we could not assess the difference between TT and DT in Asian populations. Finally,on the basis of our analysis, we do not recommend TT as conventional treatment for patients taking OACs and undergoing percutaneous coronary intervention. PMID- 26135463 TI - Comparison of three diuretic treatment strategies for patients with acute decompensated heart failure. AB - BACKGROUND: There are few prospective data available for establishing a standard diuretic administration regimen for patients with acute decompensated heart failure (ADHF). We aimed to assess the safety and efficacy of three regimens of furosemide administration in patients with ADHF with regard to diuresis, renal functions, and in-hospital outcomes. METHODS: A total of 43 patients who presented with ADHF were randomized into three groups: (a) continuous infusion (cIV) of 160 mg furosemide for 16 h/day (n = 15); (b) bolus injections (bI) of 80 mg furosemide twice a day (n = 14); (c) and administration of 160 mg furosemide plus hypertonic saline solution (HSS) as an infusion for 30 min once a day (n = 14). All regimens were continued for 48 h. Study endpoints were negative fluid balance assessed by loss of body weight, change in the serum creatinine (baseline to 48 h and baseline to compensated state), and length of hospitalization. RESULTS: There was no significant difference in the mean change in serum creatinine level at the end of 48 h between groups (p = 0.08). There was also no significant difference among groups regarding loss of body weight (p = 0.66). A significantly shorter hospitalization was observed in patients treated with HSS compared with the other groups (cIV group 6.6 +/- 3.4 days vs. bI group 7.9 +/- 4.1 days vs. HSS group 3.7 +/- 1.3 days; p < 0.01). CONCLUSION: All three furosemide regimens have similar renal safety and efficacy measures. However, administration of furosemide plus HSS may be the preferred diuretic strategy because of its shorter hospital stay. PMID- 26135464 TI - [Mitral valve interventions: Where do we stand?]. AB - Mitral valve regurgitation (MR) with resulting heart failure is one of the most prevalent types of valvular heart disease. Currently, various approaches to catheter-based therapy of MR are already available for patients deemed to be at high-risk for surgery. Most experience has been gained with the MitraClip(r) system. Technological developments in the field of catheter-based treatment of MR is advancing at a rapid pace, with treatment modalities suited for patients with both primary and secondary MR. Annuloplasty is the surgical gold standard, particularly for patients with secondary MR. For catheter-based therapy of secondary MR a distinction is made between indirect and direct annuloplasty, with the latter most closely corresponding to surgical ring implantation. Catheter based mitral valve replacement is technically feasible at present; however, experience is still limited and only few reports have been published. Technological development is markedly slower than in the field of transcatheter aortic valve replacement, predominantly owing to the far more complex structure of the mitral valve. Positive experience has already been gained with catheter based implantation of prostheses designed for the aortic valve into degenerated mitral valve bioprostheses and failed surgical mitral annuloplasty rings (valve in-valve and valve-in-ring implantation). Further approaches to catheter-based treatment of MR in high-risk surgical patients are expected in the future. PMID- 26135465 TI - [Interventional closure of atrial septal defects, patent oval foramen and ventricular septal defects]. AB - Percutaneous transcatheter closure techniques and devices for congenital intracardiac shunts have considerably improved; therefore, catheter closure is now the treatment of choice for atrial septal defects (ASD). This is technically feasible in more than 80% of patients with a secundum ASD and the success rate is higher than 99%. General anesthesia is as a rule unnecessary and the hospital stay is very short. A patent oval foramen (POF) is a potential cause of cryptogenic stroke and peripheral embolisms. The catheter occlusion has many advantages in comparison to lifelong anticoagulation therapy and for some patients it is the only therapeutic option. Randomized trials have shown that interventional closure leads to results which are comparable to drug therapy and for some occlusion systems even evidence of significant advantages compared to drug therapy was found. Even ventricular septal defects (VSD), including perimembraneous and post-myocardial infarction VSDs can be closed by catheter techniques with a high success rate. PMID- 26135466 TI - [Interventions at the tricuspid valve: What is possible?]. AB - Due to the increased life expectancy and continual improvements in cardiological treatment options, diseases of the tricuspid valve, in particular tricuspid valve insufficiency will become increasingly more recognized as an interventional target. While tricuspid stenosis is rare and can be effectively treated with balloon valvuloplasty, no effective transcatheter approach to tricuspid regurgitation (TR) has yet been established. As the tricuspid annulus is a complex and highly dynamic structure that offers little resistance, orthotopic long-term fixation of transcatheter valves with the current techniques is challenging and has not yet been performed in human patients. Alternative treatment concepts include transcatheter caval valve implantation (CAVI) to address the regurgitation of blood into the caval veins, which has resulted in hemodynamic improvement and is currently undergoing further clinical investigation. Other interventional treatment concepts are aimed at tricuspid valve repair, e.g. by annular plication with the MitralignTM device or the TriCinchTM system. In the medium-term it can be assumed that percutaneous systems and therapy options will become available for these indications whereby the functional and prognostic effects of these treatment procedures will be corroborated in the appropriate patient groups by corresponding studies. PMID- 26135467 TI - [Update on therapy of chronic heart failure. Innovations and studies from last year]. AB - Chronic heart failure is one of the most common chronic diseases worldwide with increasing prevalence and incidence. Due to the high morbidity and mortality a standardized and evidence-based therapy is crucial. The present review article gives an overview about the innovations in 2014 based on the current guidelines of the European Society of Cardiology. First, improvements in established medication regimens regarding beta blockers and mineralocorticoid receptor antagonists as well as treatment options for heart rate reduction will be explained. Second, new pharmacological developments, such as angiotensin receptor neprilysin inhibition will be discussed. Finally, new insights into common comorbidities of patients with chronic heart failure, such as atrial fibrillation and hyperkalemia will be presented. PMID- 26135469 TI - [Interventional therapy of structural heart diseases]. PMID- 26135468 TI - Platelet hyperaggregability in patients with atrial fibrillation. Evidence of a background proinflammatory milieu. AB - OBJECTIVE: Atrial fibrillation (AF) is a condition where platelet hyperaggregability is commonly present. We examined potential physiological bases for platelet hyperaggregability in a cohort of patients with acute and chronic AF. In particular, we sought to identify the impact of inflammation [myeloperoxidase (MPO) and C-reactive protein (CRP)] and impaired nitric oxide (NO) signaling. METHODS: Clinical and biochemical determinants of adenosine diphosphate (ADP)-induced platelet aggregation were sought in patients (n = 106) hospitalized with AF via univariate and multivariate analysis. RESULTS: Hyper responsiveness of platelets to ADP was directly (r = 0.254, p < 0.01) correlated with plasma concentrations of thrombospondin-1 (TSP-1), a matricellular protein that impairs NO responses and contributes to development of oxidative stress. In turn, plasma TSP-1 concentrations were directly correlated with MPO concentrations (r = 0.221, p < 0.05), while MPO concentrations correlated with those of asymmetric dimethylarginine (ADMA, r = 0.220, p < 0.05), and its structural isomer symmetric dimethylarginine (SDMA, r = 0.192, p = 0.05). Multivariate analysis identified TSP-1 (beta = 0.276, p < 0.05) concentrations, as well as female sex (beta = 0.199, p < 0.05), as direct correlates of platelet aggregability, and SDMA concentrations (beta = - 0.292, p < 0.05) as an inverse correlate. CONCLUSION: We conclude that platelet hyperaggregability, where present in the context of AF, may be engendered by impaired availability of NO, as well as via MPO-related inflammatory activation. PMID- 26135470 TI - Carbon Quantum Dots for Zebrafish Fluorescence Imaging. AB - Carbon quantum dots (C-QDs) are becoming a desirable alternative to metal-based QDs and dye probes owing to their high biocompatibility, low toxicity, ease of preparation, and unique photophysical properties. Herein, we describe fluorescence bioimaging of zebrafish using C-QDs as probe in terms of the preparation of C-QDs, zebrafish husbandry, embryo harvesting, and introduction of C-QDs into embryos and larvae by soaking and microinjection. The multicolor of C QDs was validated with their imaging for zebrafish embryo. The distribution of C QDs in zebrafish embryos and larvae were successfully observed from their fluorescence emission. the bio-toxicity of C-QDs was tested with zebrafish as model and C-QDs do not interfere to the development of zebrafish embryo. All of the results confirmed the high biocompatibility and low toxicity of C-QDs as imaging probe. The absorption, distribution, metabolism and excretion route (ADME) of C-QDs in zebrafish was revealed by their distribution. Our work provides the useful information for the researchers interested in studying with zebrafish as a model and the applications of C-QDs. The operations related zebrafish are suitable for the study of the toxicity, adverse effects, transport, and biocompatibility of nanomaterials as well as for drug screening with zebrafish as model. PMID- 26135471 TI - Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBbeta and Autophagy. AB - Autophagy inhibition is emerging as a promising anticancer strategy. We recently reported that the circadian nuclear receptor REV-ERBbeta plays an unexpected role in sustaining cancer cell survival when the autophagy flux is compromised. We also identified 4-[[[1-(2-fluorophenyl)cyclopentyl]amino]methyl]-2-[(4 methylpiperazin-1-yl)methyl]phenol, 1 (ARN5187), as a novel dual inhibitor of REV ERBbeta and autophagy. 1 had improved cytotoxicity against BT-474 breast cancer cells compared to chloroquine, a clinically relevant autophagy inhibitor. Here, we present the results of structure-activity studies, based around 1, that disclose the first class of dual inhibitors of REV-ERBbeta and autophagy. This study led to identification of 18 and 28, which were more effective REV-ERBbeta antagonists than 1 and were more cytotoxic to BT-474. The combination of optimal chemical and structural moieties of these analogs generated 30, which elicited 15 fold greater REV-ERBbeta inhibitory and cytotoxic activities compared to 1. Furthermore, 30 induced death in a panel of tumor cell lines at doses 5-50 times lower than an equitoxic amount of chloroquine but did not affect the viability of normal mammary epithelial cells. PMID- 26135472 TI - The Dry Season Shuffle: Gorges Provide Refugia for Animal Communities in Tropical Savannah Ecosystems. AB - In the wet-dry tropics, animal species face the major challenges of acquiring food, water or shelter during an extended dry season. Although large and conspicuous animals such as ungulates and waterfowl migrate to wetter areas during this time, little is known of how smaller and more cryptic animal species with less mobility meet these challenges. We fenced off the entire entrance of a gorge in the Australian tropical savanna, offering the unique opportunity to determine the composition and seasonal movement patterns of the small vertebrate community. The 1.7 km-long fence was converted to a trapline that was deployed for 18-21 days during the early dry season in each of two years, and paired traps on both sides of the fence allowed us to detect the direction of animal movements. We predicted that semi-aquatic species (e.g., frogs and turtles) would move upstream into the wetter gorge during the dry season, while more terrestrial species (e.g., lizards, snakes, mammals) would not. The trapline captured 1590 individual vertebrates comprising 60 species. There was a significant bias for captures on the outside of the fence compared to the inside for all species combined (outside/inside = 5.2, CI = 3.7-7.2), for all vertebrate classes, and for specific taxonomic groups. The opposite bias (inside/outside = 7.3, N= 25) for turtles during the early wet season suggested return migration heading into the wet season. Our study revealed that the small vertebrate community uses the gorge as a dry season refuge. The generality of this unreplicated finding could be tested by extending this type of survey to tropical savannahs worldwide. A better understanding of how small animals use the landscape is needed to reveal the size of buffer zones around wetlands required to protect both semi-aquatic and terrestrial fauna in gorges in tropical savannah woodland, and thus in ecosystems in general. PMID- 26135473 TI - No Difference in Reoperations at 2 Years Between Ceramic-on-metal and Metal-on metal THA: A Randomized Trial. AB - BACKGROUND: Hard-on-hard bearings for total hip arthroplasty continue to warrant analysis even though crosslinked polyethylene is performing very well. Ceramic-on metal (CoM) has low in vitro wear and did well in an early clinical trial. We report on a prospective, randomized, multicenter investigational device trial comparing CoM with metal-on-metal (MoM). QUESTIONS/PURPOSES: (1) Is there a difference in the number or type of revisions comparing CoM with MoM? (2) Are cobalt and chromium metal levels different for CoM and MoM THA? METHODS: Between August 2005 and October 2006, of 1015 patients screened, 390 patients were enrolled at 11 centers and randomized to 194 CoM and 196 MoM bearings. There was no difference in the preoperative patient demographics between the study groups. Mean followup was 50 months (range, 22-75 months). Seventy-two patients from two centers had metal level analysis. RESULTS: With the numbers available, there was no difference in the proportion of patients undergoing revisions between the MoM and the CoM cohorts (MOM: 3% [six of 196]; COM: 1.5% [three of 194]; p = 0.50). Four MoM revisions were unrelated to the bearing surface. Two had bearing surface related reoperations, one for an aseptic lymphocyte-dominated vasculitis associated lesion and one for elevated metal levels with acetabular malposition. None of the CoM revisions were related to the bearing surface. The metal level analysis revealed that in contrast to the CoM, the MoM bearing group had increasing values of erythrocyte and serum cobalt from 1 to 5 years (CoM erythrocyte 0.45-0.55 ppb, p = 0.11 and CoM serum 0.88-0.85, p = 0.55, and MoM erythrocyte 0.32-0.51 ppb, p < 0.01 and MoM serum 0.65-1.01 ppb, p < 0.01). In addition, the MoM cobalt levels in erythrocytes and serum at 5 years were more variable than at 1 year (erythrocyte interquartile range [IQR], 0.26-0.44 to 0.31 1.21 ppb and serum IQR, 0.42-0.80 to 0.64-2.20 ppb, p < 0.02 for both). CONCLUSIONS: Although both bearings performed well at short-term followup, the CoM bearing group had no wear-related revisions and maintained consistently low metal levels. The MoM cobalt elevations may be important considering recent reports of taper corrosion. This CoM bearing was approved by the FDA but withdrawn from the market because of low sales. If it were available, the authors would not use CoM until long-term data were available. The bearing would have to outperform crosslinked polyethylene because it is unlikely that CoM metal levels will return to normal. LEVEL OF EVIDENCE: Level I, therapeutic study. PMID- 26135474 TI - Construction of RNA-Quantum Dot Chimera for Nanoscale Resistive Biomemory Application. AB - RNA nanotechnology offers advantages to construct thermally and chemically stable nanoparticles with well-defined shape and structure. Here we report the development of an RNA-QD (quantum dot) chimera for resistive biomolecular memory application. Each QD holds two copies of the pRNA three-way junction (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor. The fixed quantity of two RNAs per QD was achieved by immobilizing the pRNA-3WJ with a Sephadex aptamer for resin binding. Two thiolated pRNA-3WJ serve as two feet of the chimera that stand on the gold plate. The RNA nanostructure served as both an insulator and a mediator to provide defined distance between the QD and gold. Immobilization of the chimera nanoparticle was confirmed with scanning tunneling microscopy. As revealed by scanning tunneling spectroscopy, the conjugated pRNA-3WJ-QD chimera exhibited an excellent electrical bistability signal for biomolecular memory function, demonstrating great potential for the development of resistive biomolecular memory and a nano-bio-inspired electronic device for information processing and computing. PMID- 26135475 TI - Zinc deficiency affects physiological and anatomical characteristics in maize leaves. AB - Zinc (Zn) is an essential microelement involved in several plant physiological processes. Therefore, it is important to identify Zn deficiencies promptly- before extensive damage occurs to the plant. The diagnostic tools that are used to identify Zn deficiencies are very important in areas where Zn deficiencies occur. Such diagnostic tools are vital for nutritional management and fertilizer recommendations. The current study investigated the effects of Zn deficiency on maize plants by recording a number of physiological and anatomical parameters. A Zn omission trial (from 0 to 22 days) was carried out to produce plants that had varying degrees of Zn deficiency. Typical symptoms of Zn deficiency (e.g. chlorotic stripes and purple shades on the edges and leaf sheath) appeared 16 days after the omission of Zn from nutrient solutions. As the time of Zn omission increased, there were significant decreases in net photosynthesis, stomatal conductance, maximal efficiency of photosystem I (evaluated by Fv/Fm), biomass (dry weight) and Zn concentrations in plants. Zinc-deficient plants also had a lower vascular bundle proportion coupled with a higher stomata density. These physiological and anatomical changes negatively impacted plant growth. Moreover, they occurred before visible symptoms of Zn deficiency were observed. Zinc concentrations were recorded for younger leaves, rather than for more mature leaves, which is usually recommended for plant analysis. The results demonstrate that the analysis of Zn in young leaves of maize is a very sensitive indicator of Zn status. PMID- 26135477 TI - Photoelectrochemical Cells Utilizing Tunable Corroles. AB - Organic dyes with their wide range of molecular structures and spectroscopic features show great promise for solar energy applications. Corroles, structural analogues to porphyrins, are highly fluorescent molecules with tunable properties. We have synthesized a series of structurally similar corroles chelating gallium and phosphorus, along with a beta-chlorinated phosphorus corrole, and determined their photophysical and electrochemical properties. The electrochemical potentials to oxidize the corroles range from 0.78 V vs NHE for the gallium corrole to 1.42 V for the beta-octachlorinated phosphorus corrole. We are interested in developing photosensitizers for water oxidation on a metal oxide-based photoanode, so the corroles were modified to contain a meso-phenyl COOH substituent for binding to metal oxide surfaces. The ability of these corrole dyes to act as photosensitizers was assessed by comparing the corroles in a model dye sensitized solar cell design. Transient absorption spectroscopy was utilized to analyze recombination dynamics and determine the kinetics of iodide oxidation. The most efficient photoelectrochemical cell was achieved for the phosphorus corrole P-2 with electrochemical properties and kinetics suitable for both photoinduced electron injection into TiO2 and oxidation of iodide. This structure-function study highlights the wide window for tuning corrole electrochemical potentials while still maintaining desirable photophysical properties, important variables when designing dyes for applications in photoelectrochemical water-oxidation cells. PMID- 26135476 TI - Echinococcosis: An Economic Evaluation of a Veterinary Public Health Intervention in Rural Canada. AB - Echinococcosis is a rare but endemic condition in people in Canada, caused by a zoonotic cestode for which the source of human infection is ingestion of parasite eggs shed by canids. The objectives of this study were to identify risk factors associated with infection and to measure the cost-utility of introducing an echinococcosis prevention program in a rural area. We analyzed human case reports submitted to the Canadian Institutes for Health Information between 2002 and 2011. Over this 10 year period, there were 48 cases associated with E. granulosus/E. canadensis, 16 with E. multilocularis, and 251 cases of echinococcosis for which species was not identified (total 315 cases). Nationally, annual incidence of echinococcosis was 0.14 cases per 100,000 people, which is likely an underestimate due to under-diagnosis and under-reporting. Risk factors for echinococcosis included female gender, age (>65 years), and residing in one of the northern territories (Nunavut, Yukon, or Northwest Territories). The average cost of treating a case of cystic echinococcosis in Canada was $8,842 CAD. Cost-utility analysis revealed that dosing dogs with praziquantel (a cestocide) at six week intervals to control cystic echinococcosis is not currently cost-effective at a threshold of $20,000-100,000 per Quality Adjusted Life Year (QALY) gained, even in a health region with the highest incidence rate in Canada ($666,978-755,051 per QALY gained). However, threshold analysis demonstrated that the program may become cost-saving at an echinococcosis incidence of 13-85 cases per 100,000 people and therefore, even one additional CE case in a community of 9000 people could result in the monetary benefits of the program outweighing costs. PMID- 26135478 TI - Vitamin D for the prevention of cardiovascular disease: Are we ready for that? AB - A general concept of clinical benefit of vitamin D supplementation has emerged from the evidence in prevention of osteoporosis. From the cardiovascular point of view, clinical benefit of such supplementation remains less clear. Studies in vitro and in animal models demonstrated the expression of vitamin D receptors in endothelial cells, vascular smooth muscle and cardiomyocytes. Vitamin D has been directly implicated in endothelium-mediated vasodilation, anti-coagulant activity and inhibition of the inflammatory response. Indirectly, it may favor the reduction of blood pressure, myocardial hypertrophy and ventricular arrhythmias. In contrast to these mechanistic findings, cross-sectional, longitudinal and small clinical trials have not been consistent in demonstrating association between cardiovascular events and vitamin D. Besides, methodological issues in the tests for serum levels of vitamin D may also contribute to this puzzle. Hence, in the current state of knowledge, it may be too early to consider or to rule out vitamin D as a tool to either estimate or mitigate residual cardiovascular risk. In this review, we discuss recent advances and potential limitations in mechanistic and clinical evidences that are outlining the framework of interaction between vitamin D and cardiovascular risk. PMID- 26135480 TI - [Not Available]. PMID- 26135479 TI - Predicting cardiovascular events ... How FIT is our crystal ball? PMID- 26135481 TI - [Not Available]. PMID- 26135482 TI - Antitumor activity of a 2-pyridinecarboxaldehyde 2-pyridinecarboxylic acid hydrazone copper complex and the related mechanism. AB - In the present study, 2-pyridinecarboxaldehyde 2-pyridinecarboxylic acid hydrazone (PPAH) was prepared and its antitumor activity was evaluated. The inhibition of proliferation of PPAH against the HepG2 and HCT-116 cell lines was less effective, yet in the presence of copper ions, the mixture demonstrated excellent antitumor activity (IC50 at 2.75+/-0.30 uM for the HepG2 cell line, and 1.90+/-0.20 uM for the HCT-116 cell line, respectively) and the new active species was confirmed to be a PPAH copper complex with a 1:1 ratio by spectral analysis. The excellent antitumor activity of the copper complex prompted us to investigate the underlying mechanism. RT-PCR was performed to detect the changes in the expression of apoptotic genes induced by PPAH and its copper complex. However, no changes were observed when the cells were treated by the agents for 24 or 48 h, indicating that ROS were unlikely involved. Cell cycle analysis showed that both PPAH and its copper complex led to S phase arrest of the cells. The sDNA relaxation assay revealed that the PPAH-copper complex displayed dual topoisomerase inhibition for type I and II. The data suggest that the inhibition of proliferation exhibited by the PPAH copper complex may stem from its dual topoisomerase inhibition, which is rarely observed for a metal complex. PMID- 26135483 TI - Effect of colloids on the occurrence, distribution and photolysis of emerging organic contaminants in wastewaters. AB - The effect of colloids on the occurrence, phase distribution and photolysis of twenty-seven emerging organic contaminants (EOCs) was studied in domestic and livestock wastewaters (DW and LW), respectively. Filtered water (<1 MUm) was separated into permeate (<1 kDa) and retentate (1 kDa-1 MUm) by cross flow ultrafiltration. Results indicated that total concentration of EOCs ranged from 1220 ng L(-1) in permeate of DW to 5065 ng L(-1) in retentate of LW. The average EOC fraction associated with colloids was 13.5% and 14.4% in DW and LW. Most of the EOCs exhibited pseudo-first-order degradation kinetics in all water samples. Control experiments using glass and quartz reactors showed that UV light was more effective on the photolysis of most EOCs. The EOCs photolysis in the three fractions of DW and LW could be accelerated or inhibited compared to ultrapure water with the enhancement factor ranging from -0.94 to 7.33. The impact of colloids on the photolysis of EOCs depended on the compound and the source of water. The photolysis of most EOCs in permeates and filtrates was generally accelerated, while inhibited in the retentates, which could be attributed to the relatively high dissolved organic carbon contents in retentates. PMID- 26135484 TI - A novel method to analyze hepatotoxic components in Polygonum multiflorum using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. AB - Polygonum multiflorum, called Heshouwu in China, is a traditional Chinese medicine used to treat various diseases. However, the administration of P. multiflorum (PM) and P. multiflorum Praeparata (PMP) causes numerous adverse effects. This study sought to analyze the toxic components of PM using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and their hepatotoxicity in L02 human liver cells. Toxicity was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) leakage, and liver enzyme secretion (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) assays. Furthermore, UPLC-Q-TOF/MS, Progenesis QI, and Makerlynx XS software analyses were used to differentiate extracts and analyze the toxic components. The order of toxicity was P. multiflorum ethanol extract (PME)>P. multiflorum water extract (PMW)>P. multiflorum Praeparata ethanol extract (PMPE)>P. multiflorum Praeparata water extract (PMPW), which was determined by MTT assay, LDH leakage, and liver enzyme secretion levels. The analysis methods suggest that PM toxicity may be associated with anthraquinone, emodin-O-(malonyl)-hex, emodin-O-glc, emodin, emodin-8-O-glc, emodin-O-(acetyl)-hex, and emodin-O-hex-sulphate. The toxic mechanisms of these components require further study. PMID- 26135485 TI - A rare presentation of Legionnaires' disease. AB - We present an interesting case of Legionnaires' disease masquerading as acute pyelonephritis, with complete absence of respiratory symptoms on admission. A 45 year-old man was diagnosed with Legionnaires' disease 2 days after presenting to hospital with dysuria and right loin pain. He became critically unwell during the hospital admission, with headache, uncontrolled fever, breathlessness, decreasing oxygen saturations and increasing oxygen requirements. A CT pulmonary angiography demonstrated right upper lobar consolidation and Legionella urinary antigen was positive. He was treated with ciprofloxacin and rifampicin and made a full recovery. PMID- 26135486 TI - Rheumatoid meningitis: a rare complication of rheumatoid arthritis. AB - We present a case of a 60-year-old Caucasian woman with a 23-year history of rheumatoid arthritis, who presented with a 2-week history of headache and cognitive/behavioural changes. On the basis of clinical features, radiology, laboratory data and meningeal biopsy, a diagnosis of rheumatoid meningitis was performed. High-dose intravenous methylprednisolone was used as initial treatment followed by oral prednisone. The patient's symptoms improved and repeat MRI scans confirmed resolution of the meningeal lesions. The clinical diagnosis of rheumatoid meningitis is difficult, but it must be considered in patients with long-standing rheumatoid arthritis presenting with neurological symptoms. Glucocorticoids or other immunomodulatory therapy are the mainstay of treatment. PMID- 26135487 TI - Abulia following an episode of cardiac arrest. AB - The word 'abulia' means a lack of will, initiative or drive. The symptoms of abulia include lack of spontaneous action and speech, reduced emotional responsiveness and social interaction, poor attention and easy distractibility. These symptoms are independent of reduced levels of consciousness or cognitive impairment. We describe a case of a socially active 72-year-old female patient who presented with symptoms of abulia which may have occurred due to damage of the frontosubcortical circuits following an episode of cardiac arrest. The patient's symptoms improved dramatically following treatment with bromocriptine. PMID- 26135488 TI - Complex congenital heart disease in a complicated and precious pregnancy. AB - A single ventricle is a rare congenital heart disease that accounts for less than 1% of all congenital heart diseases. A woman was assessed in our obstetric clinic for the first time at the gestational age of 28 weeks and found to have placental bleeding. She also had complex congenital heart disease and atrial fibrillation requiring anticoagulation. Echocardiography revealed double-inlet single ventricle with right and left atrioventricular valves entering into this chamber and levo-transposition of the great arteries. After an extensive discussion with the patient regarding the risks and benefits of anticoagulation including risk of stroke, the agreed plan was to start her on intravenous heparin with close observation and to continue pregnancy for at least 32 weeks in order to reduce the postpartum risk for the fetus. The pregnancy progressed without any further complications and the patient had elective caesarean section at 33 weeks of gestation and delivered a healthy baby boy. PMID- 26135489 TI - Catastrophic chest pain: blinded by cardiopulmonary disease. AB - A 53-year-old man with a history of diabetic foot ulcer, osteomyelitis, coronary artery disease, hypertension and hyperlipidaemia, presented with chest pain of 3 weeks duration. Eleven days earlier, the patient had had a drug-eluting stent (DES) placed in a branch of the right coronary artery (RCA) after similar chest pain, leading to the findings of a positive nuclear stress test. Since discharge, he was not compliant with taking clopidegrel (Plavix), a concern for in-stent thrombosis with recurrent myocardial ischaemia; but work up was negative and medications were restarted. Within 24 h of admission, he developed bilateral flaccid leg weakness, urine retention and loss of sensation from the umbilicus level down. MRI revealed a T4-T6 epidural abscess. Emergent decompression laminectomy and abscess drainage was completed. Neurological symptoms improved hours after surgery with complete resolution of sensory deficits. Cultures grew Streptococcus sp., treated with intravenous nafcillin for 8 weeks. He regained leg strength with continued improvement seen in rehabilitation. PMID- 26135490 TI - Hepatitis C and leptospirosis: simultaneous acute infections or recurrence of occult hepatitis C. AB - People who inject drugs are vulnerable to several infections. To the best of our knowledge, this is the first case report of a simultaneous diagnosis of leptospirosis and acute infection or recurrence of occult hepatitis C in an HIV infected drug user. We report a case of a 47-year-old Caucasian man with HIV infection, on antiretroviral therapy, and with a history of hepatitis C (positive anti-hepatitis C virus (HCV) and HCV RNA persistently negative) who was admitted with febrile acute hepatitis. He was a former injecting drug user, on opioid substitution therapy, who relapsed to injection drug use 3 weeks prior to admission. Work up revealed positive HCV RNA and Leptospira DNA in his urine. Four weeks later he had an undetectable HCV load, and also at 6 months of follow up. This case highlights the presence of two concomitant infectious aetiologies of acute hepatitis in an HIV-infected drug user. PMID- 26135491 TI - Klippel-Trenaunay syndrome, an unusual association with persistent lateral marginal vein of Servelle: colour Doppler and 256 dual-source MDCT evaluation. PMID- 26135492 TI - Acute on chronic liver failure in a patient with sickle cell anaemia (HbSS). AB - A man in his late 40s with sickle cell anaemia (HbSS) presented to the emergency department with 2 weeks of diffuse oedema, increased abdominal girth and dyspnoea. His anasarca was thought to be indicative of an acute decompensation of his known liver cirrhosis with transfusion-induced haemosiderosis. While his anasarca improved with diuresis, his direct hyperbilirubinaemia suddenly worsened without any signs of haemolysis, biliary disease or obstruction. He also developed an acute worsening in serum creatinine (1.17-7.0 mg/dL in 7 days) despite subsequent treatment for presumed hepatorenal syndrome (HRS). Given his clinical decline, the patient's goals of care were transitioned to comfort measures only. His clinical presentation and rapid liver and renal deterioration were most typical of sickle cell intrahepatic cholestasis (SCIC). SCIC can lead to rapid deterioration in renal function and can be mistaken for HRS. When SCIC is suspected, consideration of exchange transfusions should be made early. PMID- 26135493 TI - Segmental arterial mediolysis: a rare non-inflammatory cause of mesenteric bleeding. AB - Visceral abdominal aneurysms can originate from multiple disease states, including inflammatory, non-inflammatory and infectious aetiologies. It is important to follow a stepwise approach to make the correct diagnosis, because disease prognosis and management can be substantially different. We describe a 60 year-old Caucasian woman who presented from an outside facility to our University Hospital in a critical state with abdominal bleeding. She had no findings to support a vasculitic process, nor a concern for infectious aetiologies. She required a thoughtful approach and detailed imaging to diagnose a rare non inflammatory disease as the cause for her mesenteric bleeding-segmental arterial mediolysis (SAM). Through our case and discussion, we describe the importance of recognising this rare entity and of understanding how early recognition can save patients from significant morbidity and unnecessary potential harmful therapeutic options. PMID- 26135494 TI - Medical management of suspected Paecilomyces sp. deep keratitis. AB - A 74-year-old woman developed a deep keratitis presenting with an endothelial plaque without overlying stromal involvement. Owing to the characteristic clinical appearance, she was provisionally diagnosed with a Paecilomyces sp. keratitis. Corneal scrapings and aqueous humour samples were culture negative. The difficulties in diagnosing Paecilomyces sp. keratitis are discussed. The patient's keratitis was managed with a combination of topical, oral and intracameral injections of voriconazole. This medical management strategy was successful in achieving good infection control and visual outcome. We report a rarely encountered presentation of keratitis in which the clinical appearance and response to voriconazole are highly suggestive evidence of a Paecilomyces sp. keratitis. We believe the combination of topical, oral and intracameral injections of voriconazole represents a novel treatment approach for Paecilomyces sp. keratitis. Our case supports the potential for a medical approach as initial treatment in this otherwise devastating form of oculomycosis. PMID- 26135495 TI - Necrotising Candida oesophagitis after thoracic radiotherapy: significance of oesophageal wall oedema on CT. AB - Although oesophageal candidiasis is usually a superficial mucosal infection, necrotising Candida oesophagitis has been reported to cause oesophageal perforation or lung abscess. We report the case of an elderly Japanese man presenting with painless dysphagia after thoracic radiotherapy for oesophageal cancer. Non-contrast CT demonstrated segmental and oedematous thickening of the oesophageal wall. Endoscopy revealed white plaques on the oesophageal mucosa. The patient's oesophagitis responded to systemic antifungal therapy, and did not lead to oesophageal perforation. He died of recurrent oesophageal cancer several months later. The importance of severe radiation-induced oesophagitis without pain, our pathophysiological hypothesis on the local oedema caused by Candida infection and the usefulness of CT in evaluating abnormal thickening of the gastrointestinal tract are discussed separately in the article. PMID- 26135496 TI - Analysis of farmland fragmentation in China Modernization Demonstration Zone since "Reform and Openness": a case study of South Jiangsu Province. AB - Farmland is a fundamental resource for human survival and development. However, farmland fragmentation has become a serious problem, causing ecological damage and low crop production efficiency in many parts of the world. Based on remote sensing and socioeconomic data, we used landscape pattern indices, Morphological Spatial Pattern Analysis (MSPA), and Markov chain models to analyze the temporal and spatial pattern changes in farmland in South Jiangsu Province (the first "Modernization Demonstration Zone" in China) during 1985-2010. Our results demonstrated that the total farmland area decreased by ca. 24% and the farmland pattern became fragmented during 1985-2008: core farmland decreased and islet farmland increased. Additionally, the farmland patch density (PD) increased and three other landscape indices (NLSI, MESH, and COHESION) showed significant decreases. Although the fragmentation rate slowed after 2008, the convergence rate to a stationary farmland distribution became faster, and transitions tended to be less deterministic after 2000. Economic and population growth and policy changes positively contributed to this phenomenon. Therefore, the primary task of farmland protection should be to preserve contiguous farmlands and reduce scattered patches in order to promote farmland connectivity. PMID- 26135499 TI - E-learning and near-peer teaching in electrocardiogram education: a randomised trial. AB - BACKGROUND: Near-peer teaching and electronic learning (e-learning) are two effective modern teaching styles. Near-peer sessions provide a supportive learning environment that benefits both the students and the tutor. E-learning resources are flexible and easily distributed. Careful construction and regular editing can ensure that students receive all of the essential material. The aim of this study is to compare the efficacy of e-learning and near-peer teaching during the pre-clinical medical curriculum. METHODS: Thirty-nine second-year medical students were consented and randomised into two groups. Each group received teaching on electrocardiogram (ECG) interpretation from a predefined syllabus. Eighteen students completed an e-learning module and 21 students attended a near-peer tutorial. Students were asked to complete a multiple-choice exam, scored out of 50. Each student rated their confidence in ECG interpretation before and after their allocated teaching session. RESULTS: The near-peer group (84%) demonstrated a significantly higher performance than the e-learning group (74.5%) on the final assessment (p = 0.002). Prior to the teaching, the students' mean confidence scores were 3/10 in both the near-peer and e-learning groups (0, poor; 10, excellent). These increased to 6/10 in both cases following the teaching session. DISCUSSION: Both teaching styles were well received by students and improved their confidence in ECG interpretation. Near-peer teaching led to superior scores in our final assessment. Given the congested nature of the modern medical curriculum, direct comparison of the efficacy of these methods may aid course design. The aim of this study is to compare the efficacy of e-learning and near-peer teaching. PMID- 26135500 TI - Production of long chain alcohols and alkanes upon coexpression of an acyl-ACP reductase and aldehyde-deformylating oxygenase with a bacterial type-I fatty acid synthase in E. coli. AB - Microbial long chain alcohols and alkanes are renewable biofuels that could one day replace petroleum-derived fuels. Here we report a novel pathway for high efficiency production of these products in Escherichia coli strain BL21(DE3). We first identified the acyl-ACP reductase/aldehyde deformylase combinations with the highest activity in this strain. Next, we used catalase coexpression to remove toxic byproducts and increase the overall titer. Finally, by introducing the type-I fatty acid synthase from Corynebacterium ammoniagenes, we were able to bypass host regulatory mechanisms of fatty acid synthesis that have thus far hampered efforts to optimize the yield of acyl-ACP-derived products in BL21(DE3). When all these engineering strategies were combined with subsequent optimization of fermentation conditions, we were able to achieve a final titer around 100 mg L(-1) long chain alcohol/alkane products including a 57 mg L(-1) titer of pentadecane, the highest titer reported in E. coli BL21(DE3) to date. The expression of prokaryotic type-I fatty acid synthases offer a unique strategy to produce fatty acid-derived products in E. coli that does not rely exclusively on the endogenous type-II fatty acid synthase system. PMID- 26135502 TI - Electron beam induced current in the high injection regime. AB - Electron beam induced current (EBIC) is a powerful technique which measures the charge collection efficiency of photovoltaics with sub-micron spatial resolution. The exciting electron beam results in a high generation rate density of electron hole pairs, which may drive the system into nonlinear regimes. An analytic model is presented which describes the EBIC response when the total electron-hole pair generation rate exceeds the rate at which carriers are extracted by the photovoltaic cell, and charge accumulation and screening occur. The model provides a simple estimate of the onset of the high injection regime in terms of the material resistivity and thickness, and provides a straightforward way to predict the EBIC lineshape in the high injection regime. The model is verified by comparing its predictions to numerical simulations in one- and two-dimensions. Features of the experimental data, such as the magnitude and position of maximum collection efficiency versus electron beam current, are consistent with the three dimensional model. PMID- 26135504 TI - Foreword. PMID- 26135503 TI - HOXB7-S3 inhibits the proliferation and invasion of MCF-7 human breast cancer cells. AB - Homeobox B7 (HOXB7) has been found to be overexpressed in numerous types of human cancer. However, the role of HOXB7 in breast cancer remains to be elucidated. The aim of the present study was to investigate the effects of HOXB7 on the proliferation and invasion of breast cancer cells. Initially, reverse transcription quantitative polymerase chain reaction and western blotting were respectively employed to detect the mRNA and protein expression levels of the HOXB7 gene in the MDA-MB-231 and MCF-7 human breast cancer cell lines. Subsequently, small interfering RNAs designed to interfere with the expression of HOXB7 were used to knockdown the expression of HOXB7 in the MCF-7 cell line, the effects of which on cell proliferation, the apoptotic rate and invasion capacity were measured using a Cell Counting kit-8 assay, flow cytometry and transwell chambers, respectively. The results demonstrated that HOXB7 mRNA and protein were all overexpressed in MDA-MB-231 and MCF-7 breast cancer cell lines. Furthermore, HOXB7-S3 effectively inhibited the proliferation and invasion of MCF-7 breast cancer cells. In conclusion, these results demonstrated that HOXB7 may be a potential therapeutic target in human breast cancer. PMID- 26135505 TI - Endoscopic submucosal dissection for nonampullary large superficial adenocarcinoma/adenoma of the duodenum: feasibility and long-term outcomes. AB - BACKGROUND AND STUDY AIMS: The clinical benefit of endoscopic submucosal dissection (ESD) for superficial duodenal neoplasias has not yet been verified. The aims of this study were to validate the feasibility and long-term outcomes of ESD for nonampullary superficial duodenal neoplasias, larger than 20 mm. PATIENTS AND METHODS: 41 patients, with 41 nonampullary large superficial duodenal neoplasias, who underwent ESD between April 2005 to March 2013 were included in the study. The short- and long-term outcomes were retrospectively evaluated, related to tumor size, resection size, histological type, invasion depth, complete resection rate, operation time, perforation rate, delayed bleeding rate, local recurrence rate, distant metastasis, and survival rate. RESULTS: ESD was successfully completed in 38 of 41 patients (92.7 %). The median sizes of tumors and resected specimens were, respectively, 26 mm (range 20 - 70 mm) and 36.5 mm (range 23 - 80 mm). Histopathological findings showed 13 adenocarcinomas (12 mucosal, 1 submucosal) and 28 adenomas (26 high grade dysplasia, 2 low grade dysplasia). The complete resection rate was 89.5 % (34 /38 tumors). The mean operation time was 128.3minutes. Perforation during ESD occurred in 39 % and delayed bleeding occurred in 18.4 %. The median observation period was 48 months (range 3.2 - 94.1 months), and no local recurrence or distant metastasis was seen during this time, representing a disease-free survival rate of 100 %. CONCLUSIONS: ESD for nonampullary large superficial duodenal adenocarcinoma/adenoma is feasible with favorable long-term outcomes. However, because of the high complication rate due to its technical difficulty, experience and skill of the operator, along with adequate perioperative management, are essential. PMID- 26135506 TI - Use of narrow band imaging in a group endoscopy practice. AB - BACKGROUND AND STUDY AIM: Narrowband imaging (NBI) is an enhanced endoscopic optical technique which filters white light and accentuates imaging of the mucosal vasculature. Potential clinical applications of NBI include endoscopic inspection of Barrett's esophagus and endoscopic diagnosis of colorectal polyps. The degree to which NBI use has been adopted into clinical practice is unknown. The study objective was to identify the rate of NBI use in patients undergoing elective esophagoduodenoscopy (EGD) and colonoscopy, and to identify procedural factors associated with NBI use. METHODS: Elective endoscopic procedures were prospectively observed over a 2-week study period. NBI use during diagnostic EGD or colonoscopy was recorded in blinded fashion. RESULTS: NBI use was observed in 6.6 % (21/318) of procedures, including 4.7 % (5/106) of EGDs and 7.5 % (16/212) of colonoscopies. There was no difference in rate of NBI use when comparing EGD with or without biopsy, or when comparing colonoscopy with or without biopsy. NBI use was significantly higher in colonoscopy with polypectomy compared with colonoscopy without polypectomy (13 % [10/77] vs. 4.4 % [6/135], P = 0.03). NBI use varied significantly among endoscopists. There was no association between patient type (outpatient vs. inpatient), procedure start time, sedation type, or trainee involvement and use/non-use of NBI. Procedural documentation of NBI use was limited. Conclusions NBI use was observed in 6.6 % of elective endoscopic procedures and was highest in colonoscopies with polypectomy. Rate of NBI use varied significantly among endoscopists. Additional studies are needed to assess the magnitude of impact of NBI on routine endoscopic practice. PMID- 26135507 TI - Residual bioburden in reprocessed side-view endoscopes used for endoscopic retrograde cholangiopancreatography (ERCP). AB - BACKGROUND AND STUDY AIM: Worldwide some endoscopy units routinely continue to use manual reprocessing techniques for disinfection of side-view endoscopes. The aim of this study was to evaluate the outcome quality of manual reprocessing techniques for removal and inactivation of the bioburden from side-view endoscopes used for endoscopic retrograde cholangiopancreatography (ERCP) in a tertiary referral endotherapy unit in Sri Lanka. METHODS: 102 samples obtained from two different flexible side-view endoscopes (Olympus TJF Q 180V and Olympus TJF 160 R) were tested for microbial growth. Three samples were collected each time; one swab from the tip before and another after manual reprocessing. The third sample was collected by flushing the working channel with sterile normal saline after manual reprocessing. Microorganisms were identified by culturing the samples. RESULT: : After reprocessing, culture-positive rates were 20 % and 9 % for the samples obtained from the tip and the working channel of the side-view endoscopes, respectively. Klebsiella spp. and Candida spp. were found to be the commonest microorganisms in the samples from the tips and from the working channels, respectively, of the reprocessed side-view endoscopes. CONCLUSION: There is a high culture-positive rate after reprocessing of the side-view endoscopes using the manual reprocessing procedure, despite strict adherence to the protocol for reprocessing. PMID- 26135508 TI - Factors associated with delayed gastric emptying in patients with stent placement for malignant gastric outlet obstruction. AB - BACKGROUND AND STUDY AIMS: Delayed gastric emptying (DGE) is an important factor in determining the clinical outcome in patients with stent placement for malignant gastric outlet obstruction but the factors associated with DGE remain unclear. The aim of this study was to investigate whether clinicopathologic data could be used to identify the factors for DGE in such patients. PATIENTS AND METHODS: A prospective, single-arm, observational clinical study was performed in a referral hospital in Japan. A total of 54 patients with stent placement for malignant gastric outlet obstruction were enrolled. A gastric emptying scintigraphy test was performed 1 week after stent placement. The relationship between DGE and clinicopathologic factors was investigated, and also the relationship between DGE and stent patency time, eating period (when the patient was able to maintain oral intake), and survival time. RESULTS: A total of 38.9 % (21 /54) of patients had DGE. The following were identified as independent predictive factors of DGE: opioid use (odds ratio, 5.32; 95 % confidence interval [95 %CI], 1.07 - 26.41; p = 0.04), chemotherapy before stent placement (odds ratio, 8.03; 95 %CI, 1.85 - 34.95; p = 0.006), and smaller stent diameter (odds ratio, 13.59; 95 %CI, 1.72 - 107.41; p = 0.01). No relationship was found between DGE and the level of oral intake, stent patency time, eating period, and survival time. CONCLUSIONS: The factors associated with DGE after stent placement include those associated with the patient's tumor as well as factors relating to their treatment, including stenting. The clinical and functional results after stent placement appear to be unrelated to the gastric emptying findings. PMID- 26135509 TI - Evaluation of 19-gauge endoscopic ultrasonography aspiration needles using various echoendoscopes. AB - BACKGROUND AND STUDY AIMS: 19-gauge (19G) needles are used for EUS-guided tissue acquisition and interventions. The aim of the current study was to compare the functional characteristics of 19G EUS needles by means of using various echoendoscopes in a bench simulator. METHODS: The angles achieved for 19G needles (EchoTip: ET-19G, EchoTip Flex: ExF-19G, Expect: Ex-19G, and ProCore: PC-19G) and for the distal tip of the echoendoscope were evaluated for maximal angulation settings of the distal tip and the elevator. Also the resistance to advancement of the 19G needles at these endoscope settings was assessed. All evaluations were done with endoscopes in a straight and in a curved position. RESULTS: There was no large discrepancy for scope and needle angles among all echoendoscopes except for the slim Pentax scope (EG-3270UK). The ExF-19G and PC-19G needles showed better optimal angles in various conditions compared to standard 19G needles. In straight scope position, out of the 20 conditions (5 endoscopes * 2 positions of the distal tip * 2 elevator positions) the numbers of optimal angulations achieved for the Ex-19G, ExF-19G, ET-19G, and PC-19G, were 11 /20 (55 %), 20 /20 (100 %), 14 /20 (70 %) and 18 /20 (90 %), respectively. However, regarding resistance, it was impossible to advance theneedle with 14 /20 settings (70 %) for the Ex-19G, 3 /20 (15 %) for the ExF-19G, 10 /20 (50 %) for the ET-19G and 7 /20 (35 %) for the PC-19G. When the scopes were bent, with regard to the force needed to advance the needle, the numbers of optimal settings, for the Ex-19G, ExF-19G, ET-19G, and PC-19G, were 1 (5 %), 13 (65 %), 6 (30 %) and 8 (40 %), respectively. The mean maximum resistance to advancement was less for the ExF-19G than for the other needless in almost all scope and angle conditions (p < 0.05). CONCLUSION: Although there was no difference between needles, the resistance to passage was least with the flexible 19-gauge needle (ExF-19G). PMID- 26135510 TI - Evaluation of feasibility, efficiency and safety of a pure NOTES gastrojejunal bypass with gastric outlet obstruction, in an in vivo porcine model. AB - INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) gastrojejunal anastomosis (GJA) is a less invasive surgery for bariatric procedures and gastric outlet obstruction. The aim of this study was to evaluate the feasibility, efficacy, and safety of a pure NOTES gastrojejunal bypass using an in vivo porcine model. MATERIAL AND METHODS: A prospective study was performed on nine swine. A double-channel scope was used. The intervention steps were: (i) gastric incision; (ii) peritoneal access; (iii) jejunal loop selection and mobilization into the stomach; (iv) stoma creation within the gastric wall and incision; (v) anastomosis suture and pylorus closure using a T-tag prototype. The animals were assessed clinically for 3 weeks including the weight gain. The patency of the GJA was assessed at necropsy and a histological analysis was performed. RESULTS: We successfully performed all the procedures with a mean (standard deviation [SD]) operative time of 108 (26) minutes. We used a mean of 5.55 (1.30) stitches. There were no intraprocedural adverse events. Five animals survived up till euthanasia at 3 weeks (65 %). These showed a significant difference in weight curves of a loss of 3.2 kg compared with gain of 5.2 kg in a control group. Four pigs died from anastomotic dehiscence complicated by peritonitis. CONCLUSION: Gastrojejunal bypass with a pure NOTES approach is feasible. This procedure is effective, resulting in a patent anastomosis and a significant weight loss. However, the anastomotic dehiscence is a major concern because of its mortality rate, and further studies including improvement of the suturing device and the technique are needed. PMID- 26135511 TI - Intracellular siderophore but not extracellular siderophore is required for full virulence in Metarhizium robertsii. AB - Efficient iron acquisition mechanisms are fundamental for microbial survival in the environment and for pathogen virulence within their hosts. M. robertsii produces two known iron-binding natural products: metachelins, which are used to scavenge extracellular iron, and ferricrocin, which is strictly intracellular. To study the contribution of siderophore-mediated iron uptake and storage to M. robertsii fitness, we generated null mutants for each siderophore synthase gene (mrsidD and mrsidC, respectively), as well as for the iron uptake transcriptional repressor mrsreA. All of these mutants showed impaired germination speed, differential sensitivity to hydrogen peroxide, and differential ability to overcome iron chelation on growth-limiting iron concentrations. RT-qPCR data supported regulation of mrsreA, mrsidC, and mrsidD by supplied iron in vitro and during growth within the insect host, Spodoptera exigua. We also observed strong upregulation of the insect iron-binding proteins, transferrins, during infection. Insect bioassays revealed that ferricrocin is required for full virulence against S. exigua; neither the loss of metachelin production nor the deletion of the transcription factor mrsreA significantly affected M. robertsii virulence. PMID- 26135513 TI - Could nanovesicles containing a penetration enhancer clinically improve the therapeutic outcome in skin fungal diseases? AB - AIM: To study whether the formulation of an antifungal drug in nanovesicular form containing skin penetration enhancer would clinically modulate its therapeutic effectiveness. MATERIALS & METHODS: Nanovesicles containing different skin penetration enhancers 'PEVs' were prepared and loaded with sertaconazole. Penetration-enhancer vesicles were characterized for entrapment efficiency, particle size, zeta potential, elasticity, viscosity, morphology and ex vivo skin deposition. Selected formulae were preliminary tested for clinical efficacy on patients suffering from tinea corporis and tinea versicolor. RESULTS & CONCLUSION: The nanosize of the vesicles, their content of penetration enhancer and their deformable nature are three cornerstones positively influencing the therapeutic outcome of topical antifungal therapy, and hence, can be considered a promising treatment modality for skin fungal diseases. PMID- 26135512 TI - Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure. AB - Hepatocyte apoptosis and energy metabolism in mitochondria have an important role in the mechanism of acute liver failure (ALF). However, data on the association between apoptosis and the energy metabolism of hepatocytes are lacking. The current study assessed the activity of several key enzymes in mitochondria during ALF, including citrate synthase (CS), carnitine palmitoyltransferase-1 (CPT-1) and cytochrome c oxidase (COX), which are involved in hepatocyte energy metabolism. A total of 40 male Sprague-Dawley rats were divided into five groups and administered D-galactosamine and lipopolysaccharide to induce ALF. Hepatic pathology and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling examinations indicated that hepatocyte apoptosis was observed at 4 h and increased 8 h after ALF. Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion. The results measured by electron microscopy indicated that ultrastructural changes in mitochondria began at 4 h and the mitochondrial outer membrane was completely disrupted at 24 h resulting in mitochondrial collapse. The expression of CS, CPT 1 and COX was measured and analyzed using assay kits. The activity and protein expression of CS, CPT-1 and COX began to increase at 4 h, reached a peak at 8 h and decreased at 12 h during ALF. The activities of CS, CPT-1 and COX were enhanced during hepatocyte apoptosis suggesting that these enzymes are involved in the initiation and development of ALF. Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy-consuming procedure. The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF. PMID- 26135514 TI - Preparation and Characterization of Biofunctionalized Inorganic Substrates. AB - Integrating the function of biological molecules into traditional inorganic materials and substrates couples biologically relevant function to synthetic devices and generates new materials and capabilities by combining biological and inorganic functions. At this so-called "bio/abio interface," basic biological functions such as ligand binding and catalysis can be co-opted to detect analytes with exceptional sensitivity or to generate useful molecules with chiral specificity under entirely benign reaction conditions. Proteins function in dynamic, complex, and crowded environments (the living cell) and are therefore appropriate for integrating into multistep, multiscale, multimaterial devices such as integrated circuits and heterogeneous catalysts. However, the goal of reproducing the highly specific activities of biomolecules in the perturbed chemical and electrostatic environment at an inorganic interface while maintaining their native conformations is challenging to achieve. Moreover, characterizing protein structure and function at a surface is often difficult, particularly if one wishes to compare the activity of the protein to that of the dilute, aqueous solution phase. Our laboratory has developed a general strategy to address this challenge by taking advantage of the structural and chemical properties of alkanethiol self-assembled monolayers (SAMs) on gold surfaces that are functionalized with covalently tethered peptides. These surface-bound peptides then act as the chemical recognition element for a target protein, generating a biomimetic surface in which protein orientation, structure, density, and function are controlled and variable. Herein we discuss current research and future directions related to generating a chemically tunable biofunctionalization strategy that has potential to successfully incorporate the highly specialized functions of proteins onto inorganic substrates. PMID- 26135516 TI - Isolation and screening of biopolymer-degrading microorganisms from northern Thailand. AB - Forty agricultural soils were collected from Chiang Mai and Lampang provinces in northern Thailand. Bacteria, actinomycetes and fungi were isolated and screened for their ability to degrade polylactic acid (PLA), polycaprolactone (PCL) and poly(butylene succinate) (PBS) by the agar diffusion method. Sixty-seven actinomycetes, seven bacteria and five fungal isolates were obtained. The majority of actinomycetes were Streptomyces based on morphological characteristic, chemotaxonomy and 16S rRNA gene data. Seventy-nine microorganisms were isolated from 40 soil samples. Twenty-six isolates showed PLA-degradation (32.9 %), 44 isolates showed PBS-degradation (55.7 %) and 58 isolates showed PCL degradation (73.4 %). Interestingly, 16 isolates (20.2 %) could degrade all three types of bioplastics used in this study. The Amycolatopsis sp. strain SCM_MK2-4 showed the highest enzyme activity for both PLA and PCL, 0.046 and 0.023 U/mL, respectively. Moreover, this strain produced protease, esterase and lipase on agar plates. Approximately, 36.7 % of the PLA film was degraded by Amycolatopsis sp. SCM_MK2-4 after 7 days of cultivation at 30 degrees C in culture broth. PMID- 26135517 TI - Blurred Vision in a Woman Who Had Sphenoid Wing Meningioma. PMID- 26135515 TI - Involvement of an alternative oxidase in the regulation of hyphal growth and microsclerotial formation in Nomuraea rileyi CQNr01. AB - Mitochondria of Nomuraea rileyi contain an alternative oxidase (Aox), which reduces oxygen to water by accepting electrons directly from ubiquinol. Furthermore, through a transcriptional analysis, we found that an alternative oxidase (Nraox) was up-regulated during microsclerotial formation. To study the function of NrAox, Nraox was cloned from N. rileyi CQNr01. The full-length cDNA was 1266 bp with an open reading frame of 1068 bp encoding 355 amino acids. A phylogenetic analysis revealed that the NrAox of N. rileyi was closely related to Metarhizium acridum Aox. The relative expression level of the Nraox was up regulated during microsclerotial (MS) initiation. A salicylhydroxamic acid, a specific alternative oxidase inhibitor, application to the culture media severely decreased MS yields, changed the hyphae morphology and slowed the H2O2 removal. Nraox silencing caused mycelial deformations, reduced the MS yields by 97.3 % and increased MS size compared with those of the control. MS virulence was decreased to 26.2 % after Nraox was silenced. However, the Nraox-silenced strain was sensitive to environmental stress, and the growth rate was reduced under stress conditions. The results obtained suggested that Nraox is required for MS differentiation by regulating the intracellular H2O2 concentration and hypha growth. Additionally, Nraox had a great impact on the virulence of N. rileyi. PMID- 26135518 TI - A water-soluble and water-coordinated Mn(II) complex: synthesis, characterization and phantom MRI image study. AB - Ligand H4bedik was reacted with MnCl2.4H2O at pH ~ 6.5 to give a highly water soluble and water-coordinated Mn(ii) complex (). The complex was found to show r1 = 3.11 mM(-1) s(-1) per Mn(ii) at 1.4 T and 6.26 mM(-1) s(-1) per Mn(ii) at 14.1 T at 25 degrees C, pH = 7.4. In addition to r1, the r2 at 14.1 T was found to be 132.78 mM(-1) s(-1) per Mn(ii) at 25 degrees C, pH = 7.4. PMID- 26135519 TI - Donor-Promoted 1,2-Hydrogen Migration from Silicon to a Saturated Ruthenium Center and Access to Silaoxiranyl and Silaiminyl Complexes. AB - Masked silylene complexes Cp*(IXy-H)(H)RuSiH2R (R = Mes (3) and Trip (4); IXy = 1,3-bis(2,6-dimethylphenyl)imidazol-2-ylidene; "IXy-H" is the deprotonated form of IXy) exhibit metallosilylene-like (LnM-Si-R) reactivity, as observed in reactions of nonenolizable ketones, enones, and tosyl azides, to give unprecedented silaoxiranyl, oxasilacyclopentenyl, and silaiminyl complexes, respectively. Notably, these silicon-containing complexes are derived from the primary silanes MesSiH3 and TripSiH3 via activation of all three Si-H bonds. DFT calculations suggest that the mechanism of formation for the silaoxiranyl complex Cp*(IXy)(H)2Ru-Si(OCPh2)Trip (6) involves coordination of benzophenone to a silylene silicon atom, followed by a single-electron transfer in which Si-bonded, non-innocent benzophenone accepts an electron from the reactive, electron-rich ruthenium center. Importantly, this electron transfer promotes an unusual 1,2 hydrogen migration to the resulting, more electron-deficient ruthenium center via a diradicaloid transition state. PMID- 26135520 TI - Nationwide survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases in Japan: prevalence, biochemical data and treatment. AB - A nationwide epidemiologic survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases was conducted in 2010 to clarify the prevalence and the clinical presentations of the disorders. A questionnaire inquiring the experience of patients with these diseases was sent to randomly selected hospitals throughout Japan. The estimated annual incidence of the diseases was 117 cases (95% CI 75 - 160), 55 males (95% CI 30 - 81) and 62 females (95% CI 40 - 84). Tumor-induced osteomalacia (TIO) and X-linked hypophosphatemic rickets (XLH) were the most prevalent causes of acquired and genetic FGF23-related hypophosphatemic diseases, respectively. The estimated incidence of XLH was about 1 in 20,000. We have also collected clinical data of the patients by a secondary survey. These patients showed FGF23 levels of above 30 pg/mL by intact assay in the presence of hypophosphatemia. While complete resection of responsible tumors improved biochemical abnormalities in patients with TIO, treatment with phosphate and/or active vitamin D3 did not normalize serum phosphate and tubular maximum transport of phosphate in patients with XLH. Our results suggest that there is no racial difference in the incidence of XLH. While FGF23 measurement is useful for the diagnosis of FGF23-related hypophosphatemic diseases, the better management is necessary especially for patients with genetic hypophosphatemic rickets caused by excessive actions of FGF23. PMID- 26135521 TI - Transcriptional regulation of genes related to progesterone production. AB - Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert Delta(5)-Delta(4) isomerization activity to produce progesterone in a cooperative fashion with 3beta-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production. PMID- 26135522 TI - Cancer Incidence in Five Continents: Inclusion criteria, highlights from Volume X and the global status of cancer registration. AB - Cancer Incidence in Five Continents (CI5), a longstanding collaboration between the International Agency for Research on Cancer and the International Association of Cancer Registries, serves as a unique source of cancer incidence data from high-quality population-based cancer registries around the world. The recent publication of Volume X comprises cancer incidence data from 290 registries covering 424 populations in 68 countries for the registration period 2003-2007. In this article, we assess the status of population-based cancer registries worldwide, describe the techniques used in CI5 to evaluate their quality and highlight the notable variation in the incidence rates of selected cancers contained within Volume X of CI5. We also discuss the Global Initiative for Cancer Registry Development as an international partnership that aims to reduce the disparities in availability of cancer incidence data for cancer control action, particularly in economically transitioning countries, already experiencing a rapid rise in the number of cancer patients annually. PMID- 26135523 TI - Nutritional approaches for the primary prevention of allergic disease: An update. AB - The dramatic rise in early childhood allergic diseases indicates the specific vulnerability of the immune system to early life environmental changes. Dietary changes are at the centre of lifestyle changes that underpin many modern inflammatory and metabolic diseases, and therefore are an essential element of prevention strategies. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also an interest in the early life effects of specific nutrients including polyunsaturated fatty acids, oligosaccharides (soluble fibre), antioxidants, folate and other vitamins that have documented effects on immune function as well as metabolism. A better understanding of nutritional programming of immune health, nutritional epigenetics and the biological processes sensitive to nutritional exposures in early life may lead to dietary strategies that provide more tolerogenic conditions during early immune programming and reduce the burden of many inflammatory diseases, not just allergy. PMID- 26135524 TI - The clinical effectiveness and cost-effectiveness of clinical nurse specialist led hospital to home transitional care: a systematic review. AB - RATIONALE, AIMS AND OBJECTIVES: Clinical nurse specialists (CNSs) are major providers of transitional care. This paper describes a systematic review of randomized controlled trials (RCTs) evaluating the clinical effectiveness and cost-effectiveness of CNS transitional care. METHODS: We searched 10 electronic databases, 1980 to July 2013, and hand-searched reference lists and key journals for RCTs that evaluated health system outcomes of CNS transitional care. Study quality was assessed using the Cochrane Risk of Bias and Quality of Health Economic Studies tools. The quality of evidence for individual outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. We pooled data for similar outcomes. RESULTS: Thirteen RCTs of CNS transitional care were identified (n = 2463 participants). The studies had low (n = 3), moderate (n = 8) and high (n = 2) risk of bias and weak economic analyses. Post-cancer surgery, CNS care was superior in reducing patient mortality. For patients with heart failure, CNS care delayed time to and reduced death or re-hospitalization, improved treatment adherence and patient satisfaction, and reduced costs and length of re-hospitalization stay. For elderly patients and caregivers, CNS care improved caregiver depression and reduced re-hospitalization, re-hospitalization length of stay and costs. For high risk pregnant women and very low birthweight infants, CNS care improved infant immunization rates and maternal satisfaction with care and reduced maternal and infant length of hospital stay and costs. CONCLUSIONS: There is low-quality evidence that CNS transitional care improves patient health outcomes, delays re hospitalization and reduces hospital length of stay, re-hospitalization rates and costs. Further research incorporating robust economic evaluation is needed. PMID- 26135526 TI - Dermabrasion and Thin Epidermal Grafting for Treatment of Large and Small Areas of Postburn Leukoderma: A Case Series and Review of the Literature. AB - Deep burn injuries can have serious aesthetic consequences as it often results in scar tissue and pigmentary changes of the skin. The focus of this article is to report our experience and results using dermabrasion and thin split-thickness skin grafting as a technique for restoring skin pigmentation after burn injuries. Patient records were obtained from a pediatric burn hospital medical record database from 1990 to 2007. Both charts and photographs were retrospectively reviewed. The treatment was evaluated for body region treated, surface area involved, effectiveness of treatment, and number of treatments required. Indications for the procedure included longstanding depigmentation, defined as greater than 1 year, and a patient wiling to have a donor site. The areas of vitiligo were marked and dermabraded with a mechanical dermabrader. Thin epidermal grafts with a thickness of 6 thousands of an inch were harvested with an air-powered dermatome. The grafts were affixed to the dermabraded bed and dressed open or with nonstick gauze for areas of the face and wrapped for areas in the extremities. Eleven patients underwent 16 procedures. The average size of the graft per procedure was 87 cm (4-500 cm). All results were consistent and long-lasting at follow-up. Postburn leukoderma of long duration is well treated by dermabrasion and thin split-thickness skin grafting. This study is unique in describing grafting on multiple occasions and for larger areas than previously described, with two patients undergoing grafting more than 200 cm. PMID- 26135528 TI - The Fallacy of the Longevity Elixir: Negligible Senescence May be Achieved, but Not by Using Something Physical. AB - The process of aging is a continuum of degeneration which eventually leads to loss of function and clinically manifest disease. Yet, in the purely therapeutic sense, there is a distinct clinical and practical separation between age-related degenerative diseases and the background process of aging itself. It is quite possible that biomedical technologies will prove invaluable in treating or alleviating the impact of distinct age-related degenerative diseases such as cardiovascular disease, arthritis or dementia. However, when it comes to addressing the fundamental, background stochastic nature of aging, it is unlikely that regenerative biotechnologies will have any appreciable impact in continually counteracting the process. In this paper we discuss some essential conceptual obstacles, both functional and translational, which will prove overwhelming and which preclude the notion that aging can be eliminated by using physical therapies. Our reasoning is two-fold: 1. Disruptive regenerative biotechnologies interfere with the complex, dynamic topological architecture of the human organism, in a manner that will render them unsuitable for clinical use against all age-related degeneration. 2. Even if some regenerative biotechnological treatments are developed in the laboratory, the translational issues will be insurmountable, and the treatments will thus be practically unusable by the general public at large. Predictions about the near or mid-term development of rejuvenating biotechnologies are not sufficiently grounded, and do not provide a framework for effective practical achievement of negligible senescence. Instead, the answer must lie in more global and abstract methods which align well with evolutionary mechanisms based on techno-cultural societal necessities. These are likely to operate in a way which ultimately may downgrade the importance of human aging and make it an evolutionarily unnecessary process. PMID- 26135527 TI - A Survey of Mechanical Ventilator Practices Across Burn Centers in North America. AB - Burn injury introduces unique clinical challenges that make it difficult to extrapolate mechanical ventilator (MV) practices designed for the management of general critical care patients to the burn population. We hypothesize that no consensus exists among North American burn centers with regard to optimal ventilator practices. The purpose of this study is to examine various MV practice patterns in the burn population and to identify potential opportunities for future research. A researcher designed, 24-item survey was sent electronically to 129 burn centers. The chi, Fisher's exact, and Cochran-Mantel-Haenszel tests were used to determine if there were significant differences in practice patterns. We analyzed 46 questionnaires for a 36% response rate. More than 95% of the burn centers reported greater than 100 annual admissions. Pressure support and volume assist control were the most common initial MV modes used with or without inhalation injury. In the setting of Berlin defined mild acute respiratory distress syndrome (ARDS), ARDSNet protocol and optimal positive end-expiratory pressure were the top ventilator choices, along with fluid restriction/diuresis as a nonventilator adjunct. For severe ARDS, airway pressure release ventilation and neuromuscular blockade were the most popular. The most frequently reported time frame for mechanical ventilation before tracheostomy was 2 weeks (25 of 45, 55%); however, all respondents reported in the affirmative that there are certain clinical situations where early tracheostomy is warranted. Wide variations in clinical practice exist among North American burn centers. No single ventilator mode or adjunct prevails in the management of burn patients regardless of pulmonary insult. Movement toward American Burn Association-supported, multicenter studies to determine best practices and guidelines for ventilator management in burn patients is prudent in light of these findings. PMID- 26135529 TI - Basal Cell Carcinoma and Seborrheic Keratosis: When Opposites Attract. PMID- 26135530 TI - Mammary Lymphangioma. PMID- 26135531 TI - DOG1 Expression in Low-Grade Fibromyxoid Sarcoma: A Study of 11 Cases, With Molecular Characterization. AB - DOG1 is a highly sensitive marker for gastrointestinal stromal tumor (GIST) and is in the routine diagnostic antibody repertoire of many surgical pathology laboratories. Moreover, GIST is well recognized by both pathologists and clinicians in the differential diagnosis of intra-abdominal and pelvic neoplasms. Low-grade fibromyxoid sarcoma (LGFMS) is, however, much less frequently anticipated, particularly when occurring at unusual sites, because of its rarity and bland histology, particularly on core biopsy. We describe a case of a 53-year old male with a large pelvic and pararectal mass, which on biopsy showed a moderately cellular spindle cell neoplasm within fibrous stroma. Immunohistochemistry at the referring center showed diffuse and strong expression of DOG1 with negativity for other markers. After referral to a tertiary center, repeat DOG1 immunohistochemistry again showed diffuse expression, but MUC4 was also positive, and this was confirmed to be LGFMS, harboring FUS-CREB3L2 fusion transcripts by reverse transcription-polymerase chain reaction and FUS rearrangement with fluorescence in situ hybridization. In view of this we assessed DOG1 expression in 10 other LGFMS (all MUC4 positive, and 9 molecularly confirmed to harbor FUS-CREB3L2 fusion transcripts and/or FUS or EWSR1 gene rearrangement), of which 5 showed DOG1 expression in up to 75% of tumor cells, varying in intensity from weak to strong. While LGFMS and GIST are generally morphologically dissimilar, less typical variants of each exist, and both can contain bland spindled cells within fibrous stroma. As the morphologic spectrum of LGFMS is wide, and as it can occur in unusual sites and may not be well recognized by general pathologists and non-soft tissue pathologists, we highlight the potential for diagnostic confusion with GIST owing to aberrant DOG1 expression. This is clinically pertinent, as the management and prognosis of these 2 neoplasms differs significantly. PMID- 26135532 TI - Inspiratory muscle training in allogeneic hematopoietic stem cell transplantation recipients: a randomized controlled trial. AB - PURPOSE: Respiratory muscles are known to be weakened and are a cause of reduced exercise capacity in both recipients and candidates of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Effects of inspiratory muscle training (IMT) in this patient population have not been comprehensively investigated so far. The current study was planned to investigate the effects of IMT during allo HSCT on early transplantation-related outcomes. METHODS: This is a prospective, randomized controlled, double-blinded study. Thirty-eight allo-HSCT recipients, 20 of whom were allocated to the treatment group (40 % of maximal inspiratory pressure (MIP)) and 18 to the control group (5 % of MIP), received IMT for 6 weeks. Pulmonary functions, dyspnea, respiratory (MIP, maximal expiratory pressure (MEP)) and peripheral muscle strength, maximal exercise capacity using modified incremental shuttle walking test (MISWT) and submaximal exercise capacity using 6-min walking test (6-MWT), fatigue, depression, and quality of life were evaluated before and after IMT. RESULTS: The distance covered during MISWT (61.94 m) and 6-MWT (29.30 m), respiratory muscle strength (MIP 34.99 cmH2O, MEP 12.69 cmH2O), depression (-0.95), and modified Borg dyspnea scores ( 0.11) showed a significant improvement in the treatment group compared to controls (p <= 0.05). CONCLUSIONS: Inspiratory muscle training is a safe and effective intervention which improves respiratory muscle strength and exercise capacity and decreases depression and dyspnea in allo-HSCT recipients. These positive changes might be further enhanced by prolonging the duration of training or inclusion of more recipients with inspiratory muscle weakness. CLINICAL TRIAL REGISTRATION NUMBER: NCT02270346. PMID- 26135534 TI - Synthesis of Eu3+-activated BaMoO4 phosphors and their Judd-Ofelt analysis: Applications in lasers and white LEDs. AB - Eu(3+)-activated BaMoO4 phosphors were synthesized by the nitrate-citrate gel combustion method. The Rietveld refinement analysis confirmed that all the compounds were crystallized in the scheelite-type tetragonal structure with I41/a (No. 88) space group. Photoluminescence (PL) spectra of BaMoO4 phosphor reveals broad emission peaks at 465 and 605 nm, whereas the Eu(3+)-activated BaMoO4 phosphors show intense 615 nm ((5)D0->(7)F2) emission peak. Judd-Ofelt theory was applied to evaluate the intensity parameters (Omega2, Omega4) of Eu(3+)-activated BaMoO4 phosphors. The transition probabilities (AT), radiative lifetime (taurad), branching ratio (beta), stimulated emission cross-section (sigmae), gain bandwidth (sigmae*Deltalambdaeff) and optical gain (sigmae*taurad) were investigated by using the intensity parameters. CIE color coordinates confirmed that the BaMoO4 and Eu(3+)-activated BaMoO4 phosphors exhibit white and red luminescence, respectively. The obtained results revealed that the present phosphors can be a potential candidate for red lasers and white LEDs applications. PMID- 26135533 TI - Development of a Full-Thickness Human Skin Equivalent In Vitro Model Derived from TERT-Immortalized Keratinocytes and Fibroblasts. AB - Currently, human skin equivalents (HSEs) used for in vitro assays (e.g., for wound healing) make use of primary human skin cells. Limitations of primary keratinocytes and fibroblasts include availability of donor skin and donor variation. The use of physiologically relevant cell lines could solve these limitations. The aim was to develop a fully differentiated HSE constructed entirely from human skin cell lines, which could be applied for in vitro wound healing assays. Skin equivalents were constructed from human TERT-immortalized keratinocytes and fibroblasts (TERT-HSE) and compared with native skin and primary HSEs. HSEs were characterized by hematoxylin-eosin and immunohistochemical stainings with markers for epidermal proliferation and differentiation, basement membrane (BM), fibroblasts, and the extracellular matrix (ECM). Ultrastructure was determined with electron microscopy. To test the functionality of the TERT-HSE, burn and cold injuries were applied, followed by immunohistochemical stainings, measurement of reepithelialization, and determination of secreted wound-healing mediators. The TERT-HSE was composed of a fully differentiated epidermis and a fibroblast-populated dermis comparable to native skin and primary HSE. The epidermis consisted of proliferating keratinocytes within the basal layer, followed by multiple spinous layers, a granular layer, and cornified layers. Within the TERT-HSE, the membrane junctions such as corneosomes, desmosomes, and hemidesmosomes were well developed as shown by ultrastructure pictures. Furthermore, the BM consisted of a lamina lucida and lamina densa comparable to native skin. The dermal matrix of the TERT-HSE was more similar to native skin than the primary construct, since collagen III, an ECM marker, was present in TERT-HSEs and absent in primary HSEs. After wounding, the TERT-HSE was able to reepithelialize and secrete inflammatory wound-healing mediators. In conclusion, the novel TERT-HSE, constructed entirely from human cell lines, provides an excellent opportunity to study in vitro skin biology and can also be used for drug targeting and testing new therapeutics, and ultimately, for incorporating into skin-on-a chip in the future. PMID- 26135535 TI - SEM, EDX and vibrational spectroscopy of the phosphate mineral vauxite from Llallagua, Bolivia. AB - We have undertaken a vibrational spectroscopic study of vauxite from Llallagua, Bolivia. This source is important source for rare and unusual secondary phosphate minerals and is the type locality for a number of rare phosphates such as vauxite, sigloite, metavauxite and for jeanbandyite. The chemical formula was determined as (Fe0.98 Mn0.01)?0.99(Al2.00)(PO4)?2.03(OH)1.98.5.95(H2O). The Raman spectrum is dominated by intense Raman bands at 978, 1000, 1009, 1027 cm(-1) assigned to the PO4(3-) and HPO4(2-) stretching modes. Low intensity Raman bands are found at 1046, 1059, 1070, 1105, 1122, 1134 and 1150 cm(-1) and are assigned to the PO4(3-) nu3 antisymmetric stretching vibrations. Raman bands of at 498, 502, 517, 523 and 535 cm(-1) are assigned to the nu4 PO4(3-) bending modes while the Raman bands at 418, 451, 461 and 470 cm(-1) are due to the nu2 PO4(3-) bending modes. The Raman spectral profile of vauxite in the hydroxyl stretching region is broad with component bands resolved at 2918, 3103, 3328, 3402, 3555 and 3648 cm(-1). Vibrational spectroscopy enables the assessment of the molecular structure of vauxite to be undertaken. PMID- 26135536 TI - EXAFS and DFT study of the cadmium and lead adsorption on modified silica nanoparticles. AB - Silica nanoparticles of 7 nm diameter were modified with (3-aminopropyl) triethoxysilane (APTES) and characterized by CP-MAS (13)C and (29)Si NMR, FTIR, zeta potential measurements, and thermogravimetry. The particles were shown to sorb successfully divalent lead and cadmium ions from aqueous solution. Lead complexation with these silica nanoparticles was clearly confirmed by EXAFS (Extended X-ray Absorption Fine Structure) with synchrotron light measurements. Predicted Pb-N and Pb-C distances obtained from quantum-chemical calculations are in very good agreement with the EXAFS determinations. The calculations also support the higher APTES affinity for Pb(2+) compared to Cd(2+). PMID- 26135537 TI - Stannic chloride-para toluene sulfonic acid as a novel catalyst-co-catalyst system for the designing of hydroxyl terminated polyepichlorohydrin polymer: Synthesis and characterization. AB - Hydroxy terminated polyepichlorohydrin (PECH) was synthesized in good yield (85 88%) with improved functionality (2.01-2.53) and desired number average molecular weight (~3000), using a novel catalyst-co-catalyst combination. The effect of various molar ratios (4-12) of p-toluenesulphonic acid and SnCl4 on molecular weight of PECH was investigated. Different polymerization conditions like temperature, time and monomer addition rates were found to have pronounced effect on molecular weight, polydispersity and functionality of the products. The molecular weight distribution and polydispersity of the synthesized polymers were determined by Gel permeation chromatography (GPC). Absolute value of Number average molecular weight (Mn) was established with vapor pressure osmometry and structural elucidations were carried out by FT-IR and NMR spectroscopic techniques. Terminal Hydroxyl groups were quantified by acetylation method and functionality was derived from hydroxyl value and Mn. PMID- 26135538 TI - The effect of ascorbic acid on the photophysical properties and photodynamic therapy activities of zinc phthalocyanine-single walled carbon nanotube conjugate on MCF-7 cancer cells. AB - Zinc mono carboxy phenoxy phthalocyanine (1) was chemical modified with ascorbic acid via an ester bond to give ZnMCPPc-AA (2). Complexes 2 and 1 were coordinated to single walled carbon nanotubes via pi-pi interaction to give ZnMCPPc-AA-SWCNT (3) and ZnMCPPc-SWCNT (4) respectively. Complexes 2, 3 and 4 showed better photophysical properties: with improved triplet lifetimes and quantum yields, and singlet oxygen quantum yields when compared to 1 alone. The photodynamic therapy activities of complexes 1, 2, 3 and 4 were tested in vitro on MCF-7 breast cancer cells. Ascorbic acid suppresses the photodynamic therapy effect of 1, due to its ability to reduce oxidative DNA damage as a result of its potent reducing properties. The highest phototoxicity was observed for 4 which resulted in 77% decrease in cell viability, followed by 3 which resulted in 67% decrease in cell viability. This shows the importance of combination therapy, where the phthalocyanines are the photodynamic therapy agents and single walled carbon nanotubes are the photothermal therapy agents. PMID- 26135539 TI - Design and Synthesis of a Noninnocent Multitopic Catechol and Pyridine Mixed Ligand: Nanoscale Polymers and Valence Tautomerism. AB - The design and synthesis of a new redox-active ligand combining catechol and pyridine units have allowed the achievement of cobalt-based nanoscale coordination polymer particles in a single-step exhibiting a switchable valence tautomeric behavior and thermal hysteresis. The combination of polymerizing capabilities with redox-active responses in a unique ligand leads to the formation of nanoparticles exhibiting a gradual valence tautomeric interconversion in the 35-370 K temperature range. Using one single ligand to obtain these nanoparticles facilitates possible nanostructure formation methodologies. PMID- 26135540 TI - Deformation of phospholipid vesicles in an optical stretcher. AB - Phospholipid vesicles are common model systems for cell membranes. Important aspects of the membrane function relate to its mechanical properties. Here we have investigated the deformation behaviour of phospholipid vesicles in a dual beam laser trap, also called an optical stretcher. This study explicitly makes use of the inherent heating present in such traps to investigate the dependence of vesicle deformation on temperature. By using lasers with different wavelengths, optically induced mechanical stresses and temperature increase can be tuned fairly independently with a single setup. The phase transition temperature of vesicles can be clearly identified by an increase in deformation. In the case of no heating effects, a minimal model for drop deformation in an optical stretcher and a more specific model for vesicle deformation that takes explicitly into account the angular dependence of the optical stress are presented to account for the experimental results. Elastic constants are extracted from the fitting procedures, which agree with literature data. This study demonstrates the utility of optical stretching, which is easily combined with microfluidic delivery, for the future serial, high-throughput study of the mechanical and thermodynamic properties of phospholipid vesicles. PMID- 26135541 TI - Improving malignancy prediction in breast lesions with the combination of apparent diffusion coefficient and dynamic contrast-enhanced kinetic descriptors. AB - AIM: To assess how the joint use of apparent diffusion coefficient (ADC) and kinetic parameters (uptake phase and delayed enhancement characteristics) from dynamic contrast-enhanced (DCE) can boost the ability to predict breast lesion malignancy. MATERIALS AND METHODS: Breast magnetic resonance examinations including DCE and diffusion-weighted imaging (DWI) were performed on 51 women. The association between kinetic parameters and ADC were evaluated and compared between lesion types. Models with binary outcome of malignancy were studied using generalized estimating equations (GEE), (GEE), and using kinetic parameters and ADC values as malignancy predictors. Model accuracy was assessed using the corrected maximum quasi-likelihood under the independence confidence criterion (QICC). Predicted probability of malignancy was estimated for the best model. RESULTS: ADC values were significantly associated with kinetic parameters: medium and rapid uptake phase (p<0.001) and plateau and washout curve types (p=0.004). Comparison between lesion type showed significant differences for ADC (p=0.001), early phase (p<0.001), and curve type (p<0.001). The predicted probabilities of malignancy for the first ADC quartile (<=1.17*10(-3) mm(2)/s) and persistent, plateau and washout curves, were 54.6%, 86.9%, and 97.8%, respectively, and for the third ADC quartile (>=1.51*10(-3) mm(2)/s) were 3.2%, 15.5%, and 54.8%, respectively. The predicted probability of malignancy was less than 5% for 18.8% of the lesions and greater than 33% for 50.7% of the lesions (24/35 lesions, corresponding to a malignancy rate of 68.6%). CONCLUSION: The best malignancy predictors were low ADCs and washout curves. ADC and kinetic parameters provide differentiated information on the microenvironment of the lesion, with joint models displaying improved predictive performance. PMID- 26135542 TI - Docetaxel in Castration-Resistant Prostate Cancer: A Single-Centre Experience. PMID- 26135543 TI - Valproic acid-induced histone acetylation suppresses CYP19 gene expression and inhibits the growth and survival of endometrial stromal cells. AB - Endometriosis is a common type of estrogen-dependent, gynecological and chronic inflammatory disease. Epigenetics refers to changes in gene expression that occur without altering the DNA sequence or DNA content. Histone modification dominates epigenetics, and histone acetylation is the most extensively studied type of histone modification. The CYP19 gene is the gene that encodes P450 aromatase, which regulates the synthesis of estrogen. Hence, we conducted this study to investigate whether histone acetylation has an effect on CYP19 expression and whether histone acetylation is related to endometrial stromal cells (ESCs). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and chromatin immunoprecipitation assays were performed. The results revealed that valproic acid (VPA) significantly promoted histone acetylation in the ESCs, which inhibited histone acetylation in the promoter region of the CYP19 gene, thus suppressing its expression. We also noted that VPA inhibited cell viability and proliferation, and induced the apoptosis, of ESCs. The findings of our study on histone acetylation, endometriosis and the CYP19 gene provide insight which may aid in the research of histone acetylation and suggest that the CYP19 gene may be a novel therapeutic target and method for the treatment of endometriosis. PMID- 26135544 TI - Antihyperalgesic effect of duloxetine and amitriptyline in rats after peripheral nerve injury: Influence of descending noradrenergic plasticity. AB - Antidepressants such as serotonin-noradrenaline reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs) are frequently used for the management of neuropathic pain. Noradrenaline (NA) and serotonin (5-HT) increase in the spinal cord by reuptake inhibition is considered to be main mechanism of the therapeutic effect of antidepressants in neuropathic pain. In the present study, we examined the analgesic effects of duloxetine (SNRI) and amitriptyline (TCA) in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). Intraperitoneal administration of duloxetine and amitriptyline dose-dependently (3,10 and 30 mg/kg) suppressed hyperalgesia induced by SNL. In vivo microdialysis in the lumbar spinal dorsal horn revealed that NA and 5-HT concentrations increased after intraperitoneal administration of duloxetine and amitriptyline (10 mg/kg, respectively). We further determined NA and 5-HT contents in homogenized samples from the ipsilateral dorsal spinal cord after SNL. Although the NA content in SNL rats 2 weeks after ligation was higher than that in SNL rats 4 weeks after ligation, the analgesic efficacy of duloxetine and amitriptyline was similar between two groups. The present study suggests that NA/5-HT increase in the spinal cord is crucial in the antihyperalgesic effect of duloxetine and amitriptyline. The plastic change of the descending noradrenergic system does not obviously affect the analgesic efficacy of duloxetine and amitriptyline. PMID- 26135545 TI - Activation of satellite glial cells in the trigeminal ganglion contributes to masseter mechanical allodynia induced by restraint stress in rats. AB - It is commonly accepted that psychological stress contributes to the development of chronic orofacial pain. However, the neural mechanism underlying this process has remained unclear. The present study was performed to determine the involvement of satellite glia cells (SGCs) in the trigeminal ganglion (TG) in stress-induced increases in masseter muscle allodynia in rats. Using a chronic restraint stress model, we found that exposure to a 14-day stress but not a 3-day stress (6 h/day) caused decreased body weight gain, behavioral changes and marked masseter allodynia in rats. SGCs were dramatically activated, and substance P (SP) expression was significantly increased in the TG. A further analysis was undertaken to investigate the contribution of SGCs; the expression of interleukin 1beta (IL-1beta) in SGCs and interleukin-1 receptor I (IL-1RI) in neurons was significantly increased after chronic restraint stress, whereas injection of L alpha-aminoadipate (a SGC inhibitor, LAA) into the TG dramatically inhibited the overexpression of these proteins. In addition, LAA or interleukin-1 receptor antagonist (IL-1ra) administration into the TG could significantly attenuate the mechanical masseter allodynia and overexpression of SP in the TG induced by restraint stress. These results suggest that SGC activation in the TG may play a role in masseter allodynia induced by restraint stress. The over-release of IL 1beta and excessive IL1-RI expressions have close relationship with the stress induced masseter allodynia. PMID- 26135546 TI - Cognitive and motor aspects of a coincidence-timing task in Cerebral Palsy children. AB - Cerebral Palsy (CP) is a clinical syndrome involving postural and motor deficits. CP children are less accurate than healthy ones when trying to reach a target. Thus, it is difficult for CP children to perform anticipation-coincidence tasks requiring temporal and/or spatial accuracy to reach the target at the good place in the right time. The purpose of the present experiment was to further investigate CP children's ability to perform anticipation-coincidence tasks, by dissociating the cognitive from the motor aspects of the task. 11 CP children aged 6-14 years, 51 healthy children aged 6-13 years, and 13 healthy adults performed, as accurately as possible, a coincidence-timing in response to a specific sound of a musical sequence. Two experimental conditions were manipulated: In the verbal condition, temporal estimation occurred through a simple verbal response whereas in the motor condition, temporal estimation was performed by reaching a target at a self-paced velocity. In the verbal condition, CP children made similar temporal errors than their healthy counterpart. However, even though all participants underestimated stimulus occurrence, CP children also exhibited greater and more variable temporal errors when they provided a motor response for estimating stimulus occurrence. These data suggested that CP children were able to anticipate stimulus occurrence and to partially take into account their sensory-motor deficits to reach the target at this time occurrence. PMID- 26135547 TI - Effect of highly purified capsaicin on articular cartilage and rotator cuff tendon healing: An in vivo rabbit study. AB - Highly purified capsaicin has emerged as a promising injectable compound capable of providing sustained pain relief following a single localized treatment during orthopedic surgical procedures. To further assess its reliability for clinical use, the potential effect of highly purified capsaicin on articular cartilage metabolism as well as tendon structure and function warrants clarification. In the current study, rabbits received unilateral supraspinatus transection and repair with a single 1 ml injection of capsaicin (R+C), PEG-only placebo (R+P), or saline (R+S) into the glenohumeral joint (GHJ). An additional group received 1 ml capsaicin onto an intact rotator cuff (I+C). At 18 weeks post-op, cartilage proteoglycan (PG) synthesis and content as well as cell viability were similar (p>0.05) across treatment groups. Biomechanical testing revealed no differences (p>0.05) among tendon repair treatment groups. Similarly, histologic features of both cartilage and repaired tendons showed minimal differences across groups. Hence, in this rabbit model, a single injection of highly purified capsaicin into the GHJ does not induce a deleterious response with regard to cartilage matrix metabolism and cell viability, or rotator cuff healing. These data provide further evidence supporting the use of injectable, highly purified capsaicin as a safe alternative for management of postoperative pain following GHJ surgery. PMID- 26135548 TI - Comparison Studies on Sub-Nanometer-Sized Ion Clusters in Aqueous Solutions: Vibrational Energy Transfers, MD Simulations, and Neutron Scattering. AB - In this work, MD simulations with two different force fields, vibrational energy relaxation and resonant energy transfer experiments, and neutron scattering data are used to investigate ion pairing and clustering in a series of GdmSCN aqueous solutions. The MD simulations reproduce the major features of neutron scattering experimental data very well. Although no information about ion pairing or clustering can be obtained from the neutron scattering data, MD calculations clearly demonstrate that substantial amounts of ion pairs and small ion clusters (subnanometers to a few nanometers) do exist in the solutions of concentrations 0.5 M*, 3 M*, and 5 M* (M* denotes mole of GdmSCN per 55.55 mole of water). Vibrational relaxation experiments suggest that significant amounts of ion pairs form in the solutions. Experiments measuring the resonant energy transfers among the thiocyanate anions in the solutions suggest that the ions form clusters and in the clusters the average anion distance is 5.6 A (5.4 A) in the 3 M* (5 M*) Gdm-DSCN/D2O solution. PMID- 26135549 TI - Targeting alpha-synuclein as a therapeutic strategy for Parkinson's disease. AB - INTRODUCTION: alpha-Synuclein, a neuronal protein, plays a central role in the pathophysiology of Parkinson's disease (PD), the second most prevalent neurodegenerative disorder. Cases of PD have increased tremendously over the past decade necessitating the identification of new therapeutic targets to reduce patient morbidity and to improve PD patients' quality of life. AREAS COVERED: The purpose of this article is to provide an update on the role of alpha-synuclein in fibrils formation and review its role as an effective immunotherapeutic target for PD. The rapidly expanding evidence for the contribution of alpha-synuclein to the pathogenesis of PD led to the development of antibodies against the C terminus of alpha-synuclein and other molecules involved in the inflammatory signaling pathways that were found to contribute significantly to initiation and progression of the disease. EXPERT OPINION: The readers will obtain new insights on the mechanisms by which alpha-synuclein can trigger the development of PD and other related degenerative disorders along with the potential role of active and passive antibodies targeted against specific form of alpha-synuclein aggregates to clear neurotoxicity, stop the propagation of the prion-like behavior of these oligomers and reverse neuronal degeneration associated with PD. PMID- 26135550 TI - Correction: Plasmonics in the ultraviolet with the poor metals Al, Ga, In, Sn, Tl, Pb, and Bi. PMID- 26135551 TI - Effectiveness of extracorporeal shockwave therapy in three major tendon diseases. AB - BACKGROUND: Extracorporeal shockwave therapy is a conservative treatment for several painful musculoskeletal disorders. The aim of the study was the assessment of the relief from pain by the shockwave therapy in a population of consecutive patients affected by specific pathologies. MATERIALS AND METHODS: A group of consecutive patients were studied and treated. They were affected by calcific tendonitis of the shoulder (129 patients), chronic Achilles tendinopathy (102 patients), and lateral epicondylitis of the elbow (80 subjects). Each patient had 3 applications with a monthly interval, and was followed up at 1, 6, and 12 months after treatment. Results were evaluated by the numeric rating scale (NRS) in all cases, the Constant Murley Score for the assessment of the shoulder function, the American Orthopaedic Foot and Ankle Society Score for subjects affected by chronic Achilles tendinopathy, and the Oxford Elbow Score for those affected by a lateral epicondylitis of the elbow. RESULTS: One year after treatment, the results were considered satisfactory with an almost complete resolution of symptoms. There were statistically significant results at the 12 month follow-ups regarding the mean NRS score (from 6.25 to 0.2), the Constant Murley Score (from 66.7 to 79.4), the Oxford Elbow Score (from 28 to 46), and the AOFAS (from 71 to 86). CONCLUSIONS: Extracorporeal shockwave therapy may be considered a safe, economic, and effective treatment for several chronic musculoskeletal disorders, allowing satisfactory pain relief and improvement of function ability. LEVEL OF EVIDENCE: Level IV. PMID- 26135552 TI - Barriers to cardiovascular device innovation in Europe. PMID- 26135554 TI - Response to "Brachial Systolic Blood Pressure Fails to Predict Short-Term Outcome in Patients With Acute Ischemic Stroke: What About Central Systolic Pressure?". PMID- 26135553 TI - Comparative Effectiveness of a Practice-Based Comprehensive Lifestyle Intervention vs. Single Session Counseling in Hypertensive Blacks. AB - BACKGROUND: Although the efficacy of therapeutic lifestyle change (TLC) interventions are well proven, their relative effectiveness vs. single-session lifestyle counseling (SSC) on blood pressure (BP) reduction in primary care practices remains largely untested in hypertensive Blacks. The aim of this trial was to evaluate the comparative effectiveness of a comprehensive practice-based TLC intervention (motivational interviewing (MINT)-TLC) vs. SSC on BP reduction among 194 Blacks with uncontrolled hypertension. METHODS: The MINT-TLC arm included 10 weekly group classes on TLC, followed by 3 individual MINT sessions. The SSC group received 1 individual counseling session on lifestyle modification plus print versions of the intervention material. The primary outcome was within patient change in systolic BP (SBP) and diastolic BP (DBP) from baseline to 6 months. The secondary outcome was BP control at 6 months. RESULTS: Mean age of the total sample was 57 (10.2) years; 50% were women, and the mean baseline BP was 147.4/89.3mm Hg. Eighty-four percent of SSC and 77% of MINT-TLC patients completed the final 6-month assessments. BP declined significantly (P < 0.001) in both groups at 6 months with a net-adjusted systolic BP reduction of 12.9 mm Hg for the SSC group vs. 9.5mm Hg for the MINT-TLC group (P = 0.18); and diastolic BP reduction of 7.6 and 7.2mm Hg for the SSC and MINT-TLC group, respectively (P = 0.79). The between-group difference in proportion of patients with adequate BP control at 6 months was nonsignificant (P = 0.82). CONCLUSION: A significant group difference in BP between the intervention groups was not observed among a sample of hypertensive Blacks. Implementation of the pragmatic single-session intervention and its effects on utilization of healthcare services should be further evaluated. CLINICAL TRIAL REGISTRATION: Trial Number NCT01070056 at http://clinicaltrials.gov/ct2/show/NCT01070056?term=TLC+clinic&rank=1. PMID- 26135555 TI - Reductive cleavage of inert aryl C-O bonds to produce arenes. AB - Reductive cleavage of the aryl C-O bonds in various phenolic compounds and aryl ethers was achieved using LiAlH4 combined with KOtBu and without any other catalysts or additives, solely producing arenes in high yields. PMID- 26135556 TI - Characterization of a novel subtype of hippocampal interneurons that express corticotropin-releasing hormone. AB - A subset of corticotropin-releasing hormone (CRH) neurons was previously identified in the hippocampus with unknown function. Here we demonstrate that hippocampal CRH neurons represent a novel subtype of interneurons in the hippocampus, exhibiting unique morphology, electrophysiological properties, molecular markers, and connectivity. This subset of hippocampal CRH neurons in the mouse reside in the CA1 pyramidal cell layer and tract tracing studies using AAV-Flex-ChR2-tdTomato reveal dense back-projections of these neurons onto principal neurons in the CA3 region of the hippocampus. These hippocampal CRH neurons express both GABA and GAD67 and using in vitro optogenetic techniques, we demonstrate that these neurons make functional connections and release GABA onto CA3 principal neurons. The location, morphology, and importantly the functional connectivity of these neurons demonstrate that hippocampal CRH neurons represent a unique subtype of hippocampal interneurons. The connectivity of these neurons has significant implications for hippocampal function. PMID- 26135557 TI - Frequent FOS Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases With Morphologic Reappraisal. AB - Epithelioid hemangioma (EH) is a unique benign vasoformative tumor composed of epithelioid endothelial cells. Although a small subset of EHs with atypical features harbor ZFP36-FOSB fusions, no additional genetic abnormalities have been found to date in the remaining cases. On the basis of a novel FOS-LMNA gene fusion identified by RNA sequencing in an index case of a skeletal EH with typical morphology, we sought to investigate the prevalence of FOS rearrangement in a large cohort of EHs. Thus 57 additional EH cases lacking FOSB rearrangements were studied for FOS gene abnormalities by fluorescence in situ hybridization, and results were correlated with morphologic appearance and clinical presentation. The EHs were subclassified as typical (n=25), cellular (n=21), and angiolymphoid hyperplasia with eosinophilia (ALHE) (n=12) variants. The ALHE was defined as an EH with a vascular "blow-out" pattern associated with a variable degree of inflammation. There were 17 (29%) cases bearing FOS gene rearrangements among 58 cases tested, including 12 male and 5 female patients, with a mean age of 42 years. Most FOS-rearranged EHs occurred in the bone (10) and soft tissue (6), whereas only 1 case was cutaneous. The predominant anatomic site was the extremity (12), followed by trunk (3), head and neck (1), and penis (1). The incidence of FOS rearrangement was significantly higher in bone (59%, P=0.006) and lower in head and neck (5%, P=0.009). Twelve of the FOS-rearranged cases were cellular EH (P=0.001) associated with moderate mitotic activity (2 to 5/10 HPF) and milder inflammatory background. All 12 ALHE cases lacked FOS gene abnormalities, suggesting different pathogenesis. In conclusion, FOS rearrangement was present in a third of EHs across different locations and histologic variants; however, it was more prevalent in cellular EH and intraosseous lesions, compared with those in skin, soft tissue, and head and neck. This genetic abnormality can be useful in challenging cases, to distinguish cellular EHs from malignant epithelioid vascular tumors. These results also suggest that dysregulation of the FOS family of transcription factors through chromosomal translocation is as a key event in the tumorigenesis of EH except for the ALHE variant. PMID- 26135558 TI - Incidental Nodal Lymphangioleiomyomatosis Is Not a Harbinger of Pulmonary Lymphangioleiomyomatosis: A Study of 19 Cases With Evaluation of Diagnostic Immunohistochemistry. AB - Lymphangioleiomyomatosis (LAM) is a proliferation of perivascular epithelioid cells typically affecting the lung as a low-grade, destructive and progressive disease but may also be found in lymph nodes and other organs. LAM is sometimes seen as an incidental finding in lymph node dissections performed for staging of gynecologic tumors. To our knowledge, no study has investigated the clinical significance of incidental nodal LAM in relation to subsequent development of pulmonary LAM. We identified 19 patients from our institution with LAM in lymph nodes. Follow-up was available for 100% of patients and ranged from 3 to 123 months (mean 33.8 mo). All were women, ranging in age from 35 to 71 years (mean 56.3 y). None had a history of tuberous sclerosis, renal angiomyolipoma, or pulmonary LAM. LAM involvement spanned 1 to 6 nodes (mean 2), ranging from 1% to 100% of the total excised lymph nodes. The single largest focus of nodal LAM ranged from 1 to 9 mm (mean 4.3 mm) in 18 patients without evidence of persistent or recurrent nodal LAM. In the 1 patient with persistent local nodal LAM, the greatest diameter was 25 mm. Affected lymph node sites were regional pelvic and retroperitoneal chains routinely sampled in staging operations. An immunohistochemical panel of HMB45, A103, and beta-catenin was evaluated in 18 cases. HMB45 showed strong but usually focal staining in every case compared with A103, which was very focally expressed (39%) or negative. beta-catenin showed strong, diffuse cytoplasmic and membranous (non-nuclear) reactivity in 100% of cases. At the last clinic visit, all 19 patients had no manifestations of pulmonary LAM. In an absence of signs of symptoms of extranodal LAM, patients with incidentally discovered nodal LAM smaller than 10 mm are not at risk of developing pulmonary LAM. PMID- 26135559 TI - GATA3 Is a Sensitive and Specific Marker of Benign and Malignant Mesonephric Lesions in the Lower Female Genital Tract. AB - GATA3 is a transcription factor critical for embryogenesis, development, and cell differentiation. Recent studies have suggested that GATA3 is a sensitive and relatively specific biomarker for urothelial and breast carcinomas, with most Mullerian carcinomas being negative. We investigated GATA3 expression in mesonephric/Wolffian remnants and tumors in the female genital tract. A western blot was performed to assess specificity for the GATA3 antibody. GATA3 immunohistochemistry was performed on 59 formalin-fixed paraffin-embedded mesonephric samples, including 17 mesonephric remnants (MR; 11 cervical and 6 fallopian tube), 15 mesonephric hyperplasias, 21 mesonephric carcinomas, and 6 female adnexal tumors of probable Wolffian origin. Thirty conventional endocervical adenocarcinomas (ENDO-CA), 9 gastric-type cervical adenocarcinomas, and 165 endometrial adenocarcinomas (EM-CA) were also evaluated. GATA3 nuclear intensity and extent of staining was evaluated. The western blot revealed GATA3 expression in seminal vesicle and cell lines derived from breast and urothelial carcinomas, but not in other cell lines including ovarian, cervical, and endometrial cancers. All cervical MRs and mesonephric hyperplasias, 5/6 (83%) fallopian tube MRs, and 20/21 (95%) mesonephric carcinomas were GATA3 positive, although with great variability in both intensity (weak to strong) and extent (1+ to 3+) of staining. Only 1/6 (17%) female adnexal tumors of probable Wolffian origin showed weak multifocal staining. One of 30 (3%) usual-type ENDO-CAs and 3/165 EM-CAs exhibited weak-moderate GATA3 immunoreactivity; all gastric-type cervical adenocarcinomas were negative. GATA3 is a highly sensitive and specific marker for mesonephric lesions in the lower genital tract; however, its utility in the upper genital tract may be more limited. In addition, GATA3 can aid in distinguishing lower genital mesonephric lesions from usual-type and gastric-type ENDO-CAs and uterine EM-CAs. PMID- 26135560 TI - Identification of Primary Mediastinal Large B-cell Lymphoma at Nonmediastinal Sites by Gene Expression Profiling. AB - Mediastinal involvement is considered essential for the diagnosis of primary mediastinal large B-cell lymphoma (PMBL). However, we have observed cases of diffuse large B-cell lymphoma (DLBCL) with features of PMBL but without detectable mediastinal involvement. The goal was to assess our previously established gene expression profiling (GEP) signature for PMBL in classifying these cases. In a large series of DLBCL cases, we identified 24 cases with a GEP signature of PMBL, including 9 cases with a submission diagnosis of DLBCL consistent with PMBL (G-PMBL-P) and 15 cases with a submission diagnosis of DLBCL. The pathology reviewers agreed with the diagnosis in the 9 G-PMBL-P cases. Among the other 15 DLBCL cases, 11 were considered to be PMBL or DLBCL consistent with PMBL, 3 were considered to be DLBCL, and 1 case was a gray-zone lymphoma with features intermediate between DLBCL and classical Hodgkin lymphoma. All 9 G PMBL-P and 9 of the 15 DLBCL cases (G-PMBL-M) had demonstrated mediastinal involvement at presentation. Interestingly, 6 of the 15 DLBCL cases (G-PMBL-NM) had no clinical or radiologic evidence of mediastinal involvement. The 3 subgroups of PMBL had otherwise similar clinical characteristics, and there were no significant differences in overall survival. Genetic alterations of CIITA and PDL1/2 were detected in 26% and 40% of cases, respectively, including 1 G-PMBL-NM case with gain of PDL1/2. In conclusion, PMBL can present as a nonmediastinal tumor without evidence of mediastinal involvement, and GEP offers a more precise diagnosis of PMBL. PMID- 26135561 TI - SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas. AB - Ovarian small cell carcinoma of the hypercalcemic type (SCCOHT)/ovarian rhabdoid tumor is a rare and highly malignant tumor that typically occurs in young women. Up until now the diagnosis has been made on the basis of morphology without any specific immunohistochemical (IHC) markers. However, several authors have shown recently that SCCOHTs are characterized by inactivation of the SMARCA4 gene (encoding the BRG1 protein) resulting in a loss of BRG1 protein expression in IHC. We evaluated BRG1 and INI1 expression in 12 SCCOHTs and in a series of 122 tumors that could mimic SCCOHT morphologically: 9 juvenile granulosa cell tumors, 47 adult granulosa cell tumors, 33 high-grade ovarian serous carcinomas, 9 desmoplastic round cell tumors, 13 Ewing sarcomas (5 from the pelvis and 8 from soft tissues), 1 round cell sarcoma associated with CIC-DUX4 translocation from soft tissue (thigh), 1 case of high-grade endometrial stromal sarcoma of the ovary, and 9 melanomas. Forty-four adult granulosa cell tumors were interpretable by IHC. All 12 SCCOHTs were devoid of BRG1 expression and expressed INI1. All other interpretable 119 tumors showed BRG1 nuclear positivity, with variable staining proportions, ranging from 10% to 100% of positive cells (mean: 77%, median: 80%), variable intensities (weak: 5%, moderate: 37%, strong: 58%), and distributions: diffuse in 82 cases (70%) and heterogenous in 36 cases (30%). BRG1 positivity was heterogenous in desmoplastic round cell tumors and adult granulosa cell tumors. Overall, BRG1 is a useful diagnostic marker in SCCOHT, showing the absence of expression in SCCOHT. Nevertheless, the possible heterogeneity and the variable intensity of this staining warrant caution in the interpretation of BRG1 staining in biopsy specimens. PMID- 26135562 TI - Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial. AB - BACKGROUND: Cystic fibrosis (CF) is an inherited, rare autosomal recessive disease that results in chronically debilitating morbidities and high premature mortality. We evaluated how ivacaftor treatment affected CF symptoms, functioning, and well-being, as measured by the Cystic Fibrosis Questionnaire Revised (CFQ-R), a widely-used patient-reported outcome (PRO) measure. METHODS: STRIVE, a double-blind, placebo-controlled randomized trial, evaluated ivacaftor (150 mg) in CF patients aged 12+ with the G551D-CFTR mutation for 48 weeks. Treatment effect analysis used a mixed-effects repeated measures model. Treatment benefit analyses applied the cumulative distribution function and a categorical analysis of change scores ("improvement," "no change," or "decline"). Content based interpretation examined treatment effect on specific item responses. RESULTS: Data from 152 patients with a baseline CFQ-R assessment were analyzed. The treatment effect analysis favored treatment with ivacaftor over placebo on the Body Image, Eating, Health Perceptions, Physical Functioning, Respiratory, Social Functioning, Treatment Burden, and Vitality scales. Findings were supported by the analysis of categorical change. On all CFQ-R scales, the percentage of patients who improved was greater for ivacaftor. In the content based analysis, the treatment benefit was characterized by better scores across a broad range of domains. CONCLUSIONS: Results illustrate broad benefits of ivacaftor treatment across many domains: respiratory symptoms, physical and social functioning, health perceptions, and vitality, as measured by the CFQ-R. The breadth of improvements reflects the systemic mechanism of action of ivacaftor compared to other therapies. Findings support the patient-reported value of ivacaftor treatment in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00909532. PMID- 26135563 TI - Abstracting Sequences: Reasoning That Is a Key to Academic Achievement. AB - The ability to understand sequences of items may be an important cognitive ability. To test this proposition, 8 first-grade children from each of 36 classes were randomly assigned to four conditions. Some were taught sequences that represented increasing or decreasing values, or were symmetrical, or were rotations of an object through 6 or 8 positions. Control children received equal numbers of sessions on mathematics, reading, or social studies. Instruction was conducted three times weekly in 15-min sessions for seven months. In May, the children taught sequences applied their understanding to novel sequences, and scored as well or better on three standardized reading tests as the control children. They outscored all children on tests of mathematics concepts, and scored better than control children on some mathematics scales. These findings indicate that developing an understanding of sequences is a form of abstraction, probably involving fluid reasoning, that provides a foundation for academic achievement in early education. PMID- 26135564 TI - Glucagon phosphorylates serine 552 of beta-catenin leading to increased expression of cyclin D1 and c-Myc in the isolated rat liver. AB - In the last 20 years the prevalence of metabolic disorders, in particular type 2 diabetes (T2D), has more than doubled. Recently, a strong link between T2D and cancer, in particularly liver cancer has been reported. However, the mechanism connecting the development of type 2 diabetes and cancer remains unknown. One of the biggest drivers of liver cancer is alterations in the Wnt/beta-catenin pathway. In this study, we aimed to identify the effect of glucagon on beta catenin in the isolated rat liver. We found glucagon, which is substantially raised in patients with T2D, rapidly phosphorylates beta-catenin on serine 552 that is associated with increased expression of genes cyclin D1 (CCND1) and c-Myc (MYC), which are known to be involved in liver cancer. This finding may explain the increased risk of liver cancer in people with T2D. PMID- 26135565 TI - Interrelationships between Atopic Disorders in Children: A Meta-Analysis Based on ISAAC Questionnaires. AB - PURPOSE: To study the prevalence and interrelationship between asthma, allergic rhinitis and eczema using data obtained from ISAAC questionnaires. METHOD: The Medline, Pubmed Publisher, EMBASE, Google Scholar and the Cochrane Controlled Clinical Trials Register databases were systematically reviewed to evaluate epidemiological data of children with atopic disorders. To study these interrelationships, a new approach was used. Risk ratios were calculated, describing the risk of having two different atopic disorders when the child is known with one disorder. RESULTS: Included were 31 studies, covering a large number of surveyed children (n=1,430,329) in 102 countries. The calculated worldwide prevalence for asthma, eczema and allergic rhinitis is 12.00% (95% CI: 11.99-12.00), 7.88% (95% CI: 7.88-7.89) and 12.66% (95% CI: 12.65-12.67), respectively. The observed prevalence [1.17% (95% CI: 1.17-1.17)] of having all three diseases is 9.8 times higher than could be expected by chance. For children with asthma the calculated risk ratio of having the other two disorders is 5.41 (95% CI: 4.76-6.16), for children with eczema 4.24 (95% CI: 3.75-4.79), and for children with allergic rhinitis 6.20 (95% CI: 5.30-7.27). No studied confounders had a significant influence on these risk ratios. CONCLUSIONS: Only a minority of children suffers from all three atopic disorders, however this co-occurrence is significantly higher than could be expected by chance and supports a close relationship of these disorders in children. The data of this meta-analysis supports the hypothesis that there could be a fourth distinct group of children with all three disorders. Researchers and clinicians might need to consider these children as a separate group with distinct characteristics regarding severity, causes, treatment or prognosis. PMID- 26135566 TI - High prevalence of Schistosoma mansoni and other intestinal parasites among elementary school children in Southwest Ethiopia: a cross-sectional study. AB - BACKGROUND: Intestinal parasitic infections (IPIs) pose significant public health challenges in school children in developing countries. The aim of this study is to determine prevalence of intestinal parasites among elementary school children in Mizan-Aman town, southwest Ethiopia. METHODS: Institution-based cross sectional study involving 460 elementary school children in Mizan-Aman Town was conducted from May to June 2013. The school children were selected using multistage sampling technique. Data on demography and predisposing factors of IPIs were collected using pretested questionnaire. Moreover, single stool specimen was examined microscopically after wet mount and formol-ether sedimentation concentration procedures. Infection intensity of Schistosoma mansoni and soil-transmitted helminths (STHs) was estimated using Kato-Katz egg counting method. RESULTS: Age of the children ranged from 5 to 17 years. Overall, 76.7% (95%CI: 72.8-80.6) of the children harbored at least one species of intestinal parasite. Eight species of intestinal parasites were detected with S. mansoni (44.8%) and Ascaris lumbricoides (28.7%) being predominant. Helminths and pathogenic intestinal protozoa were detected in 73.9 and 7.8% of the children, respectively. After adjusting for other variables, age between 5 and 9 years (AOR, 2.6, 95%CI, 1.552-4.298), male gender (AOR, 2.1, 95%CI, 1.222-3.526), attending public school (AOR, 0.1, 95%CI, 0.060-0.256), using river/well water (AOR, 2.4, 95%CI, 0.912-6.191), irregular washing of hands before meal (AOR, 0.5, 95%CI, 0.254-0.865), consuming street food (AOR, 2.3, 95%CI, 1.341-3.813) and raw vegetables (AOR, 2.7, 95%CI, 1.594-4.540) were significantly associated with IPIs in the study participants. CONCLUSION: Prevalence of intestinal parasites among the school children was high. Deworming of the school children and continuous follow up is required. PMID- 26135567 TI - Not identifying with postnatal depression: a qualitative study of women's postnatal symptoms of distress and need for support. AB - INTRODUCTION: Diagnoses and symptoms of postnatal mental health problems are associated with adverse outcomes for women and their families. Current classification and assessment of postnatal mental health problems may not adequately address the range or combination of emotional distress experienced by mothers. This study aims to explore symptoms of mental health problems reported by new mothers and their experiences of being assessed for these. METHODS: In depth interviews with 17 women in southeast England with a baby under 1-year old who experienced a postnatal mental health problem. Data were analyzed using inductive thematic analysis. RESULTS: Women described a lack of identification with the concept of postnatal depression and felt that other forms of emotional distress were not recognized by the healthcare system. Women felt that support seeking for postnatal mental health problems needed to be normalized and that support should be available whether or not women were diagnosed. Assessment needs to be well timed and caringly implemented. DISCUSSION: Identification and recognition of symptoms and disorders other than postnatal depression need to be improved. Awareness of multiple types of distress needs to be raised both for women experiencing such distress, and for healthcare professionals, to enable them to support women at this time. Different approaches to assessment that include the range of symptoms reported should be piloted. PMID- 26135568 TI - Psychiatry - recruitment crisis or opportunity for change? AB - Psychiatry is suffering an enduring crisis in recruitment. In this editorial I discuss the reasons for this that are most pertinent to recruitment from foundation training and also review the Royal College of Psychiatrists' current 5 year plan for recruitment and what else could be done. PMID- 26135569 TI - Heroin-assisted treatment: has a controversial treatment come of age??. AB - This editorial considers the findings of the systematic review of heroin-assisted treatment, with six different studies from six different countries, published in this issue. The meta-analysis focuses on supervised injected heroin and reports significant crime reduction and an overall cost-effectiveness of treatment. Despite this body of evidence, policy makers remain reluctant to develop this treatment further. The question remains, what else is required to convince policy makers of the value of such treatment for severe and refractory heroin dependence? PMID- 26135571 TI - Heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addiction?. AB - BACKGROUND: Supervised injectable heroin (SIH) treatment has emerged over the past 15 years as an intensive treatment for entrenched heroin users who have not responded to standard treatments such as oral methadone maintenance treatment (MMT) or residential rehabilitation. AIMS: To synthesise published findings for treatment with SIH for refractory heroin-dependence through systematic review and meta-analysis, and to examine the political and scientific response to these findings. METHOD: Randomised controlled trials (RCTs) of SIH treatment were identified through database searching, and random effects pooled efficacy was estimated for SIH treatment. Methodological quality was assessed according to criteria set out by the Cochrane Collaboration. RESULTS: Six RCTs met the inclusion criteria for analysis. Across the trials, SIH treatment improved treatment outcome, i.e. greater reduction in the use of illicit 'street' heroin in patients receiving SIH treatment compared with control groups (most often receiving MMT). CONCLUSIONS: SIH is found to be an effective way of treating heroin dependence refractory to standard treatment. SIH may be less safe than MMT and therefore requires more clinical attention to manage greater safety issues. This intensive intervention is for a patient population previously considered unresponsive to treatment. Inclusion of this low-volume, high-intensity treatment can now improve the impact of comprehensive healthcare provision. PMID- 26135573 TI - Therese Raquin by Emile Zola: surgical method in psychiatry - reflection. PMID- 26135575 TI - Invited commentary on ... Lithium treatment and risk for dementia in adults with bipolar disorder. AB - Alzheimer's disease clinical trials are failing at an alarming rate, highlighting the desperate need for novel thinking to combat this escalating health crisis. A recent large-scale population study indicates that lithium treatment reduces dementia development, supporting preclinical mechanistic evidence that this commonly used agent might be clinically valuable in dementia. PMID- 26135576 TI - Kaleidoscope. PMID- 26135579 TI - Annexin A5 Promoter Haplotype M2 Is Not a Risk Factor for Recurrent Pregnancy Loss in Northern Europe. AB - INTRODUCTION: Annexin A5 is an essential component of placental integrity that may potentially mediate susceptibility to phenotypes of compromised pregnancy. A promoter haplotype termed M2 of the coding gene ANXA5 has been implicated in various pregnancy complications such as preeclampsia and recurrent pregnancy loss (RPL), however with inconclusive results. STUDY SUBJECTS AND METHODS: A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia and Denmark to estimate the RPL disease risk of the M2 haplotype in Northern Europe. Comparative prevalence of the studied ANXA5 genetic variants in human populations was estimated based on the 1000 Genomes Project (n = 675, whole-genome sequencing data) and the KORA S3 500K dataset of South German samples (n = 1644, genome-wide genotyping data). RESULTS: Minor allele frequency of common polymorphisms in ANXA5 promoter was up to two fold lower among Estonian RPL subjects than fertile controls. The M2 haplotype was not associated with RPL and a trend for decreased prevalence was observed among RPL patients compared to controls both in Estonia (8.1% vs 15.2%, respectively) and Denmark (9.7% vs 12.6%). The high M2 prevalence in fertile controls was consistent with estimations for European and East Asian populations (9.6%-16.0%). CONCLUSIONS: This study cautions to consider the M2 haplotype as a deterministic factor in early pregnancy success because: i) no RPL disease risk was associated with the haplotype in two clinically well-characterized RPL case control study samples, ii) high prevalence of the haplotype among fertile controls and world-wide populations is inconsistent with the previously proposed severe impact on early pregnancy success, iii) weak impact of M2 haplotype on the production of ANXA5 protein has been established by others. PMID- 26135581 TI - Risks of Antibiotic Exposures Early in Life on the Developing Microbiome. PMID- 26135580 TI - Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal Nets. AB - OBJECTIVE: Perineuronal nets (PN) form a specialized extracellular matrix around certain highly active neurons within the central nervous system and may help to stabilize synaptic contacts, promote local ion homeostasis, or play a protective role. Within the ocular motor system, excitatory burst neurons and omnipause neurons are highly active cells that generate rapid eye movements - saccades; both groups of neurons contain the calcium-binding protein parvalbumin and are ensheathed by PN. Experimental lesions of excitatory burst neurons and omnipause neurons cause slowing or complete loss of saccades. Selective palsy of saccades in humans is reported following cardiac surgery, but such cases have shown normal brainstem neuroimaging, with only one clinicopathological study that demonstrated paramedian pontine infarction. Our objective was to test the hypothesis that lesions of PN surrounding these brainstem saccade-related neurons may cause saccadic palsy. METHODS: Together with four controls we studied the brain of a patient who had developed a permanent selective saccadic palsy following cardiac surgery and died several years later. Sections of formalin-fixed paraffin embedded brainstem blocks were applied to double-immunoperoxidase staining of parvalbumin and three different components of PN. Triple immunofluorescence labeling for all PN components served as internal controls. Combined immunostaining of parvalbumin and synaptophysin revealed the presence of synapses. RESULTS: Excitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation. INTERPRETATION: Our findings support current models and experimental studies of the brainstem saccade-generating neurons and indicate that damage to PN may permanently impair the function of these neurons that the PN ensheathe. How a postulated hypoxic mechanism could selectively damage the PN remains unclear. We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease. PMID- 26135582 TI - Design of the POINT study: Pharmacotherapy Optimisation through Integration of a Non-dispensing pharmacist in a primary care Team (POINT). AB - BACKGROUND: In the Netherlands, 5.6 % of acute hospital admissions are medication related. Almost half of these admissions are potentially preventable. Reviewing medication in patients at risk in primary care might prevent these hospital admissions. At present, implementation of medication reviews in primary care is suboptimal: pharmacists lack access to patient information, pharmacists are short of clinical knowledge and skills, and working processes of pharmacists (focus on dispensing) and general practitioners (focus on clinical practice) match poorly. Integration of the pharmacist in the primary health care team might improve pharmaceutical care outcomes. The aim of this study is to evaluate the effect of integration of a non-dispensing pharmacist in general practice on the safety of pharmacotherapy in the Netherlands. METHODS: The POINT study is a non-randomised controlled intervention study with pre-post comparison in an integrated primary care setting. We compare three different models of pharmaceutical care provision in primary care: 1) a non-dispensing pharmacist as an integral member of a primary care team, 2) a pharmacist in a community pharmacy with a predefined training in performing medication reviews and 3) a pharmacist in a community pharmacy (care as usual). In all models, GPs remain accountable for individual medication prescription. In the first model, ten non-dispensing clinical pharmacists are posted in ten primary care practices (including 5 - 10 000 patients each) for a period of 15 months. These non-dispensing pharmacists perform patient consultations, including medication reviews, and share responsibility for the pharmaceutical care provided in the practice. The two other groups consist of ten primary care practices with collaborating pharmacists. The main outcome measurement is the number of medication-related hospital admissions during follow-up. Secondary outcome measurements are potential medication errors, drug burden index and costs. Parallel to this study, a qualitative study is conducted to evaluate the feasibility of introducing a NDP in general practice. DISCUSSION: As the POINT study is a large-scale intervention study, it should provide evidence as to whether integration of a non-dispensing clinical pharmacist in primary care will result in safer pharmacotherapy. The qualitative study also generates knowledge on the optimal implementation of this model in primary care. Results are expected in 2016. TRIAL REGISTRATION NUMBER: NTR4389 , The Netherlands National Trial Register, 07-01-2014. PMID- 26135584 TI - A content analysis of food advertising on Turkish television. AB - The aim of this study was to conduct a comprehensive content analysis of Television (TV) food advertising and compare various food advertisements on free to-air Turkish national TV channels by broadcast time (duration) and frequency over the period of a week (19-25 April 2012). TV food advertisements were the unit of content analysis in this study. Each advertisement identified as promoting a food product was analysed for content; non-food advertisements were not analysed, although they were counted as a proportion of the advertisements aired. We recorded all programmes for 4 h each per day (7 p.m.-11 p.m.), totalling 84 h. Five types of food-related advertisements were identified (basic foods, junk foods, meat products, beverages and fast food), and six types of non food advertisements. The Student t-test and ANOVA were used to compare the mean broadcast time of all prime time advertising for the two groups. The mean broadcast times for prime time, non-food advertisements showed a statistically significant difference (p < 0.05). This difference is related to the prime time period 7 p.m.-8 p.m. being considered dinner time for most Turkish families. Additionally, the number and broadcast times of beverage advertisements increased during this time period, while the broadcast time per beverage advertisement decreased (ratio = 20.8 s per ads). As a result, TV food advertising increased not only during dinner time but also in overall broadcast time (per advertisement). These findings may be useful for explaining how advertising can negatively influence food choices, thereby increasing public awareness of the need for health messages targeting obesity. PMID- 26135583 TI - Recollection-Based Retrieval Is Influenced by Contextual Variation at Encoding but Not at Retrieval. AB - In this article, we investigated the effects of variations at encoding and retrieval on recollection. We argue that recollection is more likely to be affected by the processing that information undergoes at encoding than at retrieval. To date, manipulations shown to affect recollection were typically carried out at encoding. Therefore, an open question is whether these same manipulations would also affect recollection when carried out at retrieval, or whether there is an inherent connection between their effects on recollection and the encoding stage. We therefore manipulated, at either encoding or retrieval, fluency of processing (Experiment 1)-typically found not to affect recollection and the amount of attentional resources available for processing (Experiments 2 and 3)-typically reported to affect recollection. We found that regardless of the type of manipulation, recollection was affected more by manipulations carried out at encoding and was essentially unaffected when these manipulations were carried out at retrieval. These findings suggest an inherent dependency between recollection-based retrieval and the encoding stage. It seems that because recollection is a contextual-based retrieval process, it is determined by the processing information undergoes at encoding-at the time when context is bound with the items-but not at retrieval-when context is only recovered. PMID- 26135585 TI - Problematics of empowerment: sex worker HIV prevention in the Pacific. AB - A recent overview of HIV/STI prevention programmes for sex workers in the Pacific region indicates that, despite a regional policy shift from universal to targeted interventions, Pacific Island countries currently lack core HIV/STI prevention services for sex workers. Across the region, condom distribution, peer outreach and support services for sex workers have ceased even in countries where such programmes had previously existed. This article cautions that the endorsement of empowerment projects does not negate the important role of condom access in HIV and STI prevention efforts for Pacific sex workers. While community empowerment underpins, and is essential to the sustainability of, effective interventions, it does not constitute an adequate form of HIV and STI prevention in and of itself. We contend that in the context of the Pacific Islands, timely and effective HIV prevention measures must specifically attend to the implementation of, and sustained support for, behavioural interventions such as sex-worker-specific peer education, condom and lubricant distribution, and access to appropriate sexual health services. Further, the responsibility for delivery of these should not be borne solely by fledgling sex worker organizations and communities. The evolution of targeted interventions in the Pacific and the current lack of funded condom distribution programmes highlight a more generalizable imperative within HIV prevention to ensure that behaviour change efforts are not considered to be extraneous to, or rendered redundant by, empowerment-based interventions. PMID- 26135586 TI - A 2-year young adult obesity prevention trial in the US: Process evaluation results. AB - Our objective was to conduct a process evaluation of the CHOICES (Choosing Healthy Options in College Environments and Settings) study, a large, randomized, controlled trial designed to prevent unhealthy weight gain in young adults (aged 18-35) attending 2-year community colleges in the USA. The 24-month intervention consisted of participation in an academic course and a social networking and support website. Among intervention participants, completion rates for most course activities were >80%, reflecting a high level of dose received. Course retention and participant satisfaction were also high. Engagement results, however, were mixed with less than half of participants in the online and hybrid sections of the course reporting that they interacted with course materials >=3 h/week, but 50-75% reporting that they completed required lessons 'all/very thoroughly'. Engagement in the website activities was also mixed with more than half of intervention participants logging onto the website during the first month, but then declining to 25-40% during the following 23 months of the intervention. Intervention engagement is a challenge of online interventions and a challenge of working with the young adult age group in general. Additional research is needed to explore strategies to support engagement among this population, particularly for relatively long intervention durations. PMID- 26135588 TI - Monitoring of Persons with Risk for Exposure to Ebola Virus Disease - United States, November 3, 2014-March 8, 2015. AB - On October 27, 2014, CDC released guidance for monitoring and movement of persons with potential Ebola virus disease (Ebola) exposure in the United States. For persons with possible exposure to Ebola, this guidance recommended risk categorization, daily monitoring during the 21-day incubation period, and, for persons in selected risk categories, movement restrictions. The purpose of the guidance was to delineate methods for early identification of symptoms among persons at potential risk for Ebola so that they could be isolated, tested, and if necessary, treated to improve their chance of survival and reduce transmission. Within 7 days, all 50 states and two local jurisdictions (New York City [NYC] and the District of Columbia [DC]) had implemented the guidelines. During November 3, 2014-March 8, 2015, a total of 10,344 persons were monitored for up to 21 days with >99% complete monitoring. This public health response demonstrated the ability of state, territorial, and local health agencies to rapidly implement systems to effectively monitor thousands of persons over a sustained period. PMID- 26135587 TI - A systematic review of non-pharmacological interventions for primary Sjogren's syndrome. AB - OBJECTIVE: To evaluate the effects of non-pharmacological interventions for primary SS (pSS) on outcomes falling within the World Health Organization International Classification of Functioning Disability and Health domains. METHODS: We searched the following databases from inception to September 2014: Cochrane Database of Systematic Reviews; Medline; Embase; PsychINFO; CINAHL; and clinical trials registers. We included randomized controlled trials of any non pharmacological intervention. Two authors independently reviewed titles and abstracts against the inclusion/exclusion criteria and independently assessed trial quality and extracted data. RESULTS: A total of 1463 studies were identified, from which 17 full text articles were screened and 5 studies were included in the review; a total of 130 participants were randomized. The included studies investigated the effectiveness of an oral lubricating device for dry mouth, acupuncture for dry mouth, lacrimal punctum plugs for dry eyes and psychodynamic group therapy for coping with symptoms. Overall, the studies were of low quality and at high risk of bias. Although one study showed punctum plugs to improve dry eyes, the sample size was relatively small. CONCLUSION: Further high-quality studies to evaluate non-pharmacological interventions for PSS are needed. PMID- 26135589 TI - Monitoring Exposure to Ebola and Health of U.S. Military Personnel Deployed in Support of Ebola Control Efforts - Liberia, October 25, 2014-February 27, 2015. AB - In response to the unprecedented Ebola virus disease (Ebola) outbreak in West Africa, the U.S. government deployed approximately 2,500 military personnel to support the government of Liberia. Their primary missions were to construct Ebola treatment units (ETUs), train health care workers to staff ETUs, and provide laboratory testing capacity for Ebola. Service members were explicitly prohibited from engaging in activities that could result in close contact with an Ebola infected patient or coming in contact with the remains of persons who had died from unknown causes. Military units performed twice-daily monitoring of temperature and review of exposures and symptoms ("unit monitoring") on all persons throughout deployment, exit screening at the time of departure from Liberia, and post-deployment monitoring for 21 days at segregated, controlled monitoring areas on U.S. military installations. A total of 32 persons developed a fever during deployment from October 25, 2014, through February 27, 2015; none had a known Ebola exposure or developed Ebola infection. Monitoring of all deployed service members revealed no Ebola exposures or infections. Given their activity restrictions and comprehensive monitoring while deployed to Liberia, U.S. military personnel constitute a unique population with a lower risk for Ebola exposure compared with those working in the country without such measures. PMID- 26135590 TI - Sodium Intake Among U.S. Adults - 26 States, the District of Columbia, and Puerto Rico, 2013. AB - Excess sodium intake is a major risk factor for hypertension, and subsequently, heart disease and stroke, the first and fifth leading causes of U.S. deaths, respectively. During 2011-2012, the average daily sodium intake among U.S. adults was estimated to be 3,592 mg, above the Healthy People 2020 target of 2,300 mg. To support strategies to reduce dietary sodium intake, 2013 Behavioral Risk Factor Surveillance System (BRFSS) data from states and territories that implemented the new sodium-related behavior module were assessed. Across 26 states, the District of Columbia (DC), and Puerto Rico, 39%-73% of adults reported taking action (i.e., watching or reducing sodium intake) (median = 51%), and 14%-41% reported receiving advice from a health professional to reduce sodium intake (median = 22%). Compared with adults without hypertension, a higher percentage of adults with self-reported hypertension reported taking action and receiving advice to reduce sodium intake. For states that implemented the module, these results can serve as a baseline to monitor the effects of programs designed to reduce sodium intake. PMID- 26135591 TI - Introduction of Inactivated Poliovirus Vaccine and Switch from Trivalent to Bivalent Oral Poliovirus Vaccine - Worldwide, 2013-2016. AB - Since the 1988 World Health Assembly resolution to eradicate poliomyelitis (polio), transmission of wild poliovirus (WPV) has been interrupted in all countries except Afghanistan, Nigeria, and Pakistan. No polio cases caused by WPV type 2 (WPV2) have been identified since 1999, and WPV type 3 has not been detected since November 11, 2012. This progress has been achieved through widespread use of oral poliovirus vaccine (OPV), most commonly trivalent OPV (tOPV), which contains types 1, 2, and 3 live, attenuated polioviruses. OPV polioviruses can undergo genetic changes during intestinal replication, and rarely, in communities with low vaccination coverage, such changes can result in vaccine-derived polioviruses (VDPVs) capable of causing paralytic polio. Eliminating the risk for polio caused by VDPVs will require stopping all OPV use. Among 686 cases of paralytic polio caused by circulating VDPVs (cVDPVs) that have been detected since 2006, type 2 cVDPVs (cVDPV2s) accounted for >97%. To eliminate the risks posed by cVDPV2s, OPV serotype 2 will be withdrawn from all immunization activities and programs through a global, synchronized replacement of all tOPV with bivalent OPV (bOPV) containing only types 1 and 3 polioviruses. This switch from tOPV to bOPV is scheduled for April 2016. To reduce the risk for cVDPV2 outbreaks and to facilitate responses to outbreaks that do occur, injectable trivalent inactivated poliovirus vaccine (IPV) is being introduced into routine immunization schedules in all countries. As of June 24, 2015, 90 (46%) of 194 World Health Organization (WHO) member states were using IPV, 102 (53%) had established dates for the introduction of IPV, and two (1%) intended to introduce IPV in 2015 but had not set dates for doing so. In addition to IPV introduction in all countries, careful synchronization of the switch from tOPV to bOPV will be needed within and across all 156 countries currently using tOPV. This report summarizes progress in introducing IPV and preparations for the switch from tOPV to bOPV. PMID- 26135592 TI - Pd-Catalyzed Regiodivergent Hydroesterification of Aryl Olefins with Phenyl Formate. AB - An effective Pd-catalyzed regiodivergent hydroesterification of aryl olefins with phenyl formate is described. Either linear or branched phenyl arylpropanoates can be obtained in good yields with high regioselectivities by the judicious choice of ligand without the use of toxic CO gas. PMID- 26135593 TI - Pharmacokinetics, Safety and Bioequivalence of Levetiracetam Intravenous Infusion and Oral Tablets in Healthy Chinese Subjects. AB - BACKGROUND AND OBJECTIVE: Levetiracetam is available in China as adjunctive oral therapy for partial-onset seizures. This study was conducted to evaluate the bioequivalence between single-dose intravenous infusion and oral levetiracetam 1500 mg (Part A), and to assess the pharmacokinetics of multiple-dose intravenous infusion at the same dose (Part B) in healthy Chinese subjects. METHODS: Part A was an open-label, crossover comparison (intravenous vs. oral), while Part B was a double-blind, parallel-group study of intravenous levetiracetam versus intravenous placebo administered for 5 days. RESULTS: Bioequivalence was demonstrated between the 45-min intravenous infusion and oral tablets, with geometric mean area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUC(infinity)) 492.3 and 506.8 MUg.h/mL, and geometric mean maximum concentration (Cmax) 65.12 and 55.93 MUg/mL for intravenous infusion and oral dosing, respectively. Linear pharmacokinetics were demonstrated (geometric least squares mean AUC during the dosing interval tau at steady state (AUC(tau,ss)) 475.6 MUg.h/mL; geometric least-squares mean AUC(infinity) after single dose 501.7 MUg.h/mL; linearity factor = 0.948). Geometric mean Cmax (77.44 MUg/mL) and AUC(tau,ss) (475.6 MUg.h/mL) of intravenous infusion levetiracetam 1500 mg after multiple doses were within the expected range, based on their respective single dose values and the terminal half-life of levetiracetam after a single dose (7.13 h). A theoretical accumulation of approximately 40% would be expected after multiple doses, which is consistent with the calculated accumulation of 18.0 and 43.5% (Rmax and R(AUC), respectively). CONCLUSIONS: Intravenous infusion of levetiracetam is bioequivalent to oral levetiracetam in healthy Chinese subjects and is a suitable alternative for levetiracetam administration in patients who are temporarily unable to take their medication orally. PMID- 26135594 TI - Fidaxomicin Pharmacokinetics in Humans: Is There a Role of Biliary Excretion? PMID- 26135595 TI - gammadelta T Cells Are Required for M2 Macrophage Polarization and Resolution of Ozone-Induced Pulmonary Inflammation in Mice. AB - We examined the role of gammadelta T cells in the induction of alternatively activated M2 macrophages and the resolution of inflammation after ozone exposure. Wildtype (WT) mice and mice deficient in gammadelta T cells (TCRdelta-/- mice) were exposed to air or to ozone (0.3 ppm for up to 72h) and euthanized immediately or 1, 3, or 5 days after cessation of exposure. In WT mice, M2 macrophages accumulated in the lungs over the course of ozone exposure. Pulmonary mRNA abundance of the M2 genes, Arg1, Retnla, and Clec10a, also increased after ozone. In contrast, no evidence of M2 polarization was observed in TCRdelta-/- mice. WT but not TCRdelta-/- mice expressed the M2c polarizing cytokine, IL-17A, after ozone exposure and WT mice treated with an IL-17A neutralizing antibody exhibited attenuated ozone-induced M2 gene expression. In WT mice, ozone-induced increases in bronchoalveolar lavage neutrophils and macrophages resolved quickly after cessation of ozone exposure returning to air exposed levels within 3 days. However, lack of M2 macrophages in TCRdelta-/- mice was associated with delayed clearance of inflammatory cells after cessation of ozone and increased accumulation of apoptotic macrophages in the lungs. Delayed restoration of normal lung architecture was also observed in TCRdelta-/- mice. In summary, our data indicate that gammadelta T cells are required for the resolution of ozone-induced inflammation, likely because gammadelta T cells, through their secretion of IL 17A, contribute to changes in macrophage polarization that promote clearance of apoptotic cells. PMID- 26135597 TI - [Advanced and continuing education in neuroradiology]. PMID- 26135596 TI - Cognitive remediation: potential novel brain-based treatment for bipolar disorder in children and adolescents. AB - Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data show that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD. PMID- 26135598 TI - Biosynthesis of Panaefluoroline B from the Cultured Mycobiont of Amygdalaria panaeola. AB - Panaefluoroline B (2) is a fluorescent yellowish-green pigment produced by the cultured mycobiont of a lichen, Amygdalaria panaeola. Panaefluoroline B (2) has an isoquinoline skeleton, a C5 unit, and an amino acid, glycine, in its structure. The biosynthetic pathway of 2 was revealed by feeding experiments using [1-(13)C]-sodium acetate and [1,2-(13)C2][(15)N]-glycine. The analysis of labeling patterns of 2 and its mass spectrum suggested the isoquinoline part is biosynthesized via the acetate-malonate pathway with glycine as the nitrogen source and that the C5 unit originates from the mevalonate pathway. PMID- 26135600 TI - A Review of Patient Lifting Interventions to Reduce Health Care Worker Injuries. AB - Health care workers suffer from musculoskeletal disorders at a significantly higher rate than workers in other industries. Consequently, a growing demand for patient handling devices to reduce worker injury has evolved. This article reviews the literature regarding interventions designed to reduce injuries among health care workers. A PubMed search was conducted using the terms "occupational health [Mesh Terms] patient lifting." Fourteen articles were identified that assessed interventions to improve worker safety. Of the 14 articles, 7 discussed technological interventions, 4 educational approaches, and 3 policy change. All three types of interventions were generally effective at improving worker safety, with the ideal intervention consisting of elements of all three types. Although adopting a new intervention may be expensive, the reduction in workers' compensation costs associated with injured nurses can easily outweigh the costs of interventions. PMID- 26135602 TI - Chikungunya Virus. AB - A mosquito-borne viral disease that is creating increased concern globally is Chikungunya virus (CHIKV). Occupational and environmental health nurses should educate workers about this emerging viral infection. PMID- 26135599 TI - An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. AB - Dengue virus (DENV), a global disease, is divided into four serotypes (DENV1-4). Cross-reactive and non-neutralizing antibodies against envelope (E) protein of DENV bind to the Fcgamma receptors (FcgammaR) of cells, and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent enhancement (ADE). Identification and modification of enhancing epitopes may mitigate enhancement of DENV infection. In this study, we characterized the cross-reactive DB21-6 and DB39-2 monoclonal antibodies (mAbs) against domain I-II of DENV; these antibodies poorly neutralized and potently enhanced DENV infection both in vitro and in vivo. In addition, two enhancing mAbs, DB21-6 and DB39-2, were observed to compete with sera antibodies from patients infected with dengue. The epitopes of these enhancing mAbs were identified using phage display, structural prediction, and mapping of virus-like particle (VLP) mutants. N8, R9, V12, and E13 are the reactive residues of DB21-6, while N8, R9, and E13 are the reactive residues of DB39-2. N8 substitution tends to maintain VLP secretion, and decreases the binding activity of DB21-6 and DB39-2. The immunized sera from N8 substitution (N8R) DNA vaccine exerted greater neutralizing and protective activity than wild type (WT)-immunized sera, both in vitro and in vivo. Furthermore, treatment with N8R-immunized sera reduced the enhancement of mortality in AG129 mice. These results support identification and substitution of enhancing epitope as a novel strategy for developing safe dengue vaccines. PMID- 26135603 TI - Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways. AB - Hepatocyte growth factor (HGF) regulates satellite cell activation, proliferation, and differentiation. We analyzed the dose-dependent effects of HGF on myogenesis. Murine C2C12 and human donor-derived skeletal muscle myoblasts were treated with 0, 2, or 10 ng/ml HGF followed by assessment of proliferation and differentiation. HGF (2 ng/ml) significantly promoted cell division, but reduced myogenic commitment and fusion. Conversely, 10 ng/ml HGF reduced proliferative capability, but increased differentiation. c-Met expression analysis revealed significantly decreased expression in differentiating cells cultured with 2 ng/ml HGF, but increased expression in proliferating cells with 10 ng/ml HGF. Mitogen-activated protein kinase (MAPKs: ERK, JNK, or p38K) and phosphatidylinositol-3-kinase (PI3K) inhibition abrogated the HGF-stimulated increase in cell number. Interestingly, PI3K and p38 kinase facilitated the negative effect of HGF on proliferation, while ERK inhibition abrogated the HGF mediated decrease in differentiation. Dose-dependent effects of HGF are mediated by changes in c-Met expression and downstream MAPK and PI3K signalling. PMID- 26135604 TI - An Ultrahigh-Resolution Digital Image Sensor with Pixel Size of 50 nm by Vertical Nanorod Arrays. AB - The pixel size limit of existing digital image sensors is successfully overcome by using vertically aligned semiconducting nanorods as the 3D photosensing pixels. On this basis, an unprecedentedly high-resolution digital image sensor with a pixel size of 50 nm and a resolution of 90 nm is fabricated. The ultrahigh resolution digital image sensor can heavily impact the field of visual information. PMID- 26135605 TI - Quercetin Induces Dose-Dependent Differential Morphological and Proliferative Changes in Rat Uteri in the Presence and in the Absence of Estrogen. AB - Quercetin could have profound effects on uterine morphology and proliferation, which are known to be influenced by estrogen. This study investigated the effect of quercetin on these uterine parameters in the presence and in the absence of estrogen. Ovariectomized adult female rats received peanut oil, quercetin (10, 50, and 100 mg/kg/day), estrogen, or estrogen+quercetin (10, 50, or 100 mg/kg/day) treatment for 7 consecutive days. At the end of the treatment, uteri were harvested for histological and molecular biological analyses. Distribution of proliferative cell nuclear antigen (PCNA) protein in the uterus was observed by immunohistochemistry. Levels of expression of PCNA protein and mRNA in uterine tissue homogenates were determined by Western blotting and real-time polymerase chain reaction, respectively. Our findings indicated that administration of 10 mg/kg/day of quercetin either alone or with estrogen resulted in decreased uterine expression of PCNA protein and mRNA with the percentage of PCNA-positive cells in uterine luminal and glandular epithelia markedly reduced compared with estrogen-only treatment. Changes in uterine morphology were the opposite of changes observed following estrogen treatment. Treatment with 100 mg/kg/day of quercetin either alone or with estrogen resulted in elevated PCNA protein and mRNA expression. In addition, the percentages of PCNA-positive cells in the epithelia, which line the lumen and glands, were increased with morphological features mimicking changes that occur following estrogen treatment. Following 50 mg/kg/day quercetin treatment, the changes observed were in between those changes that occur following 10 and 100 mg/kg/day quercetin treatment. In conclusion, changes in uterine morphology and proliferation following 10 mg/kg/day quercetin treatment could be attributed to quercetin's antiestrogenic properties, while changes that occur following 100 mg/kg/day quercetin treatment could be attributed to quercetin's estrogenic properties. PMID- 26135606 TI - RNAi therapeutics for brain cancer: current advancements in RNAi delivery strategies. AB - Malignant primary brain tumors are aggressive cancerous cells that invade the surrounding tissues of the central nervous system. The current treatment options for malignant brain tumors are limited due to the inability to cross the blood brain barrier. The advancements in current research has identified and characterized certain molecular markers that are essential for tumor survival, progression, metastasis and angiogenesis. These molecular markers have served as therapeutic targets for the RNAi based therapies, which enable site-specific silencing of the gene responsible for tumor proliferation. However, to bring about therapeutic success, an efficient delivery carrier that can cross the blood brain barrier and reach the targeted site is essential. The current review focuses on the potential of targeted, non-viral and viral particles containing RNAi therapeutic molecules as delivery strategies specifically for brain tumors. PMID- 26135607 TI - Characterization of real-world patients with low fractional flow reserve immediately after drug-eluting stents implantation. AB - Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for coronary artery disease has been validated. The present study aimed to identify the variables that influence FFR immediately after drug-eluting stents (DESs) implantation. We retrospectively analyzed 167 patients, who had been implanted with DESs at 6 Japanese institutions and had obtained the FFR values before and immediately after PCI. Intravascular ultrasound (IVUS) was used to build a PCI strategy and to decide the completion of the PCI procedure in all case. Patients were categorized into the following 2 groups according to FFR after PCI: the low FFR (<=0.80) group and the high FFR (>0.80) group. Despite successful PCI evaluated by coronary angiography and IVUS, 18.6 % of real-world patients were in the low FFR group. The proportion of the left anterior descending artery (LAD) was significantly greater in the low FFR group than in the high FFR group (87.1 vs 56.6 %; P < 0.01). Multivariate logistic regression analysis revealed that the LAD-to-non-LAD odds ratio for a low FFR (<=0.80) was 7.34 (95 % CI 1.63-32.95; P < 0.01) after adjustment for FFR value before PCI, suggesting that it is difficult to improve the hemodynamics of the LAD lesions even after successful PCI. The LAD was the strongest contributor to the inadequate recovery of FFR immediately after PCI, thus eliciting heed when treating the LAD lesions. PMID- 26135608 TI - Gold Nanobipyramid-Directed Growth of Length-Variable Silver Nanorods with Multipolar Plasmon Resonances. AB - We report on a method for the preparation of uniform and length-variable Ag nanorods through anisotropic Ag overgrowth on high-purity Au nanobipyramids. The rod diameters can be roughly tailored from ~20 nm to ~50 nm by judicious selection of differently sized Au nanobipyramids. The rod lengths can be tuned from ~150 nm to ~550 nm by varying the Ag precursor amount during the overgrowth process and/or by anisotropic shortening through mild oxidation. The controllable aspect ratios, high purity, and high dimensional uniformity of these Ag nanorods enable the observation of Fabry-Perot-like multipolar plasmon resonance modes in the colloidal suspensions at the ensemble level, which has so far been demonstrated only on Au nanorods prepared electrochemically with anodic aluminum oxide templates. Depending on the mode order and geometry of the Ag nanorods, the multipolar plasmon wavelengths can be readily tailored over a wide spectral range from the visible to near-infrared region. We have further elucidated the relationships between the multipolar plasmon wavelengths and the geometric dimensions of the Ag nanorods at both the ensemble and single-particle levels. Our results indicate that the Au nanobipyramid-directed, dimensionally controllable Ag nanorods will be an attractive and promising candidate for developing multipolar plasmon-based devices and applications. PMID- 26135609 TI - Releases of surgically deafened homing pigeons indicate that aural cues play a significant role in their navigational system. AB - Experienced homing pigeons with extirpated cochleae and lagenae were released from six sites in upstate New York and western Pennsylvania on 17 days between 1973 and 1975 by William T. Keeton and his co-workers at Cornell University. The previously unpublished data indicate that departure directions of the operated birds were significantly different from those of sham-operated control birds (314 total), indicating that aural cues play an important part in the pigeon's navigational system. Moreover, propagation modeling of infrasonic waves using meteorological data for the release days supports the possibility that control birds used infrasonic signals to determine their homeward direction. Local acoustic 'shadow' zones, therefore, could have caused initial disorientation of control birds at release sites where they were normally well oriented. Experimental birds plausibly employed an alternate 'route-reversal' strategy to return home perhaps using their ocular-based magnetic compass. We suggest, based on Keeton's results from another site of long-term disorientation, that experienced pigeons depend predominantly on infrasonic cues for initial orientation, and that surgical removal of their aural sense compelled them to switch to a secondary navigational strategy. PMID- 26135610 TI - [Systematic Readability Analysis of Medical Texts on Websites of German University Clinics for General and Abdominal Surgery]. AB - Background: Besides the function as one of the main contact points, websites of hospitals serve as medical information portals. As medical information texts should be understood by any patients independent of the literacy skills and educational level, online texts should have an appropriate structure to ease understandability. Materials and Methods: Patient information texts on websites of clinics for general surgery at German university hospitals (n = 36) were systematically analysed. For 9 different surgical topics representative medical information texts were extracted from each website. Using common readability tools and 5 different readability indices the texts were analysed concerning their readability and structure. The analysis was furthermore stratified in relation to geographical regions in Germany. Results: For the definite analysis the texts of 196 internet websites could be used. On average the texts consisted of 25 sentences and 368 words. The reading analysis tools congruously showed that all texts showed a rather low readability demanding a high literacy level from the readers. Conclusion: Patient information texts on German university hospital websites are difficult to understand for most patients. To fulfill the ambition of informing the general population in an adequate way about medical issues, a revision of most medical texts on websites of German surgical hospitals is recommended. PMID- 26135611 TI - [Can Topical Negative Pressure Therapy be Performed as a Cost-Effective General Surgery Procedure in the German DRG System?]. AB - INTRODUCTION: Topical negative pressure therapy (TNPT) has been established for surgical wound therapy with different indications. Nevertheless, there is only sparse evidence regarding its therapeutic superiority or cost-effectiveness in the German DRG system (G-DRG). This study was designed to analyse the cost effectiveness of TNPT in the G-DRG system with a focus on daily treatment costs and reimbursement in a general surgery care setting. PATIENTS/MATERIALS AND METHODS: In this retrospective study, we included 176 patients, who underwent TNPT between 2007 and 2011 for general surgery indications. Analysis of the cost effectiveness involved 149 patients who underwent a simulation to calculate the reimbursement with or without TNPT by a virtual control group in which the TNP procedure was withdrawn for DRG calculation. This was followed by a calculation of costs for wound dressings and TNPT rent and material costs. Comparison between the "true" and the virtual group enabled calculation of the effective remaining surplus per case. RESULTS: Total reimbursement by included TNPT cases was 2,323 ,70.04 ?. Costs for wound dressings and TNPT rent were 102,669.20 ?. In 41 cases there was a cost-effectiveness (27.5%) with 607,422.03 ? with TNP treatment, while the control group without TNP generated revenues of 442,015.10 ?. Costs for wound dressings and TNPT rent were 47,376.68 ?. In the final account we could generate a cost-effectiveness of 6759 ? in 5 years per 149 patients by TNPT. In 108 cases there was no cost-effectiveness (72.5%). CONCLUSION: TNPT applied in a representative general surgery setting allows for wound therapy without a major financial burden. Based on the costs for wound dressings and TNPT rent, a primarily medically based decision when to use TNPT can be performed in a balanced product cost accounting. This study does not analyse the superiority of TNPT in wound care, so further prospective studies are required which focus on therapeutic superiority and cost-effectiveness. PMID- 26135612 TI - [Management of Hemoptysis: Results of an Algorithm-Based Interdisciplinary Treatment Scheme]. AB - INTRODUCTION: Hemoptysis is a worrying symptom for the majority of patients, is frequently a sign for a severe disease and can develop into a life-threatening situation. Various therapeutic methods and medical specialties can be involved in the management of these patients. Guidelines or evidence-based recommendations on this issue are not available. Based on our long-term experience and considering all established diagnostic and therapeutic means, we propose an algorithm to manage this condition. PATIENTS AND METHODS: This is a retrospective analysis of a cohort from a single thoracic surgical institution. Data regarding the used diagnostic and therapeutic methods with focus on outcome parameters are presented. Based on our experience and the published data we discuss the proposed algorithm. RESULTS: Between 01.2009 and 12.2013, 204 patients were hospitalised and treated for hemoptysis. Malignancies were the most frequent (50 %) cause of hemoptysis, followed by infectious/inflammatory diseases (25 %), cardiovascular disorders (6 %), rare (12 %) and unclear (7 %) circumstances. In 71 cases the bleeding stopped spontaneously, in 124 (61 %) one invasive measure (interventional bronchoscopy 43, bronchial artery embolisation 34 or operation 12) or a combination of methods (35 combinations of two or all three methods) were necessary to stop the hemoptysis. Six patients died without intervention. The bronchial artery embolisation showed a 79 % success rate and a morbidity of 11 %. Lung resections were performed in 30 cases (morbidity 43 %, mortality 0 %). The mortality directly due to massive hemoptysis was 4.5 %. CONCLUSIONS: Even small hemoptysis can be the warning signal for serious conditions and immediate diagnostic evaluation and therapy, preferentially in an inpatient setting, is often mandatory. A prompt diagnostic bronchoscopy is advocated. The therapeutic method of first choice is non-surgical for the most cases (interventional bronchoscopy, bronchial artery embolisation). Lung resections retain an important role in the management of hemoptysis and are the only available therapy for some diseases. It is advisable to delay surgery until the bleeding is controlled and the patient is stabilised. Best results for managing hemoptysis can be achieved with a multidisciplinary approach (interventional bronchoscopy, angiology and thoracic surgery) in a high expertise centre. PMID- 26135613 TI - [Factors with Impact on the Outcome after Surgical Interventions for Abdominal Aortic Aneurysms]. AB - BACKGROUND: Since its introduction, endovascular aortic aneurysm repair (EVAR) has proved as a favourable alternative to open surgery (OR) in the treatment of abdominal aortic aneurysms (AAA). Long-term outcomes of EVAR and OR are similar while complications are more likely to develop after EVAR. Risk factors for mortality and complications after AAA surgery have been identified, however, a general overview is lacking. METHODS: In a systematic literature search via PubMed, we identified publications on the topic of factors influencing the postoperative outcome of AAA surgery. RESULTS: Patient age > 80 years was found to be a significant predictor of increased mortality, whereas the influence of aneurysm diameter on OR remains moderate, the outcome of EVAR performed in AAA > 6.5 cm is associated with higher mortality and increased complication rates. In patients with ruptured AAA the postoperative mortality is higher than in those with intact aneurysms. Preoperative haemodynamic instability has a crucial influence on patient outcome and is strongly associated with intra- and postoperative death. The prevalence of cardiovascular co-morbidity leads to increased long-term mortality. Preoperative statin medication was found to reduce short- and long-term mortality by the factor of 0.5. Patients suffering from chronic lung disease such as COPD and patients with a deficiency in renal function are more likely to experience adverse events including death. While the prevalence of cerebrovascular disease is associated with an increase in mortality by the factor of 1.5 or higher, findings on patients with diabetes mellitus are conflicting with no definite point to be made. CONCLUSION: Several factors influencing the outcome of surgery for AAA present a condition developed from factors involved in the pathogenesis of AAA. The impact of non-disease factors like patient age and aneurysm diameter can be reduced by the means of population wide screening for AAA, and optimised treatment of disease-related risk factors can reduce mortality. Studies comparing the outcome of EVAR and OR in patients with risk factors should be performed to support decision-making about the ideal individual treatment. PMID- 26135614 TI - ["EVAR First" also in "Fit-for-Open-Repair" Patients? - 'CON' Statement]. AB - Our own long-term results and the numerous published data from the literature indicate that after open surgery or endovascular treatment, there is no significant difference with regard to morbidity and lethality in the early and long-term postoperative outcome of patients with low comorbidity ("low-risk" patients or patients "fit for open repair"). The advantage of endovascular aneurysmatic "repair" (EVAR) is revealed only in risk patients resulting in the fact that patient selection has a decisive role for the prognosis. Typical EVAR associated complications such as late ruptures and secondary conversions, the re intervention rate post-EVAR between 20 and 30 % as well as the appropriate training of young vascular surgeons favour a not too stringent limitation, i.e., preservation of open abdominal aneurysm surgery in suitable patients and indications. PMID- 26135615 TI - Infrared Spectroscopy of OH..CH3OH: Hydrogen-Bonded Intermediate Along the Hydrogen Abstraction Reaction Path. AB - Substantial non-Arrhenius behavior has been previously observed in the low temperature reaction between the hydroxyl radical and methanol. This behavior can be rationalized assuming the stabilization of an association adduct in the entrance channel of the reaction, from which barrier penetration via quantum mechanical tunneling produces the CH3O radical and H2O. Helium nanodroplet isolation and a serial pick-up technique are used to stabilize the hydrogen bonded prereactive OH..CH3OH complex. Mass spectrometry and infrared spectroscopy are used to confirm its production and probe the OH stretch vibrations. Stark spectroscopy reveals the magnitude of the permanent electric dipole moment, which is compared to ab initio calculations that account for wide-amplitude motion in the complex. The vibrationally averaged structure has Cs symmetry with the OH moiety hydrogen bonded to the hydroxyl group of methanol. Nevertheless, the zero point level of the complex exhibits a wave function significantly delocalized over a bending coordinate leading to the transition state of the CH3O producing reaction. PMID- 26135617 TI - Circulating classical CD14++CD16- monocytes predict shorter time to initial treatment in chronic lymphocytic leukemia patients: Differential effects of immune chemotherapy on monocyte-related membrane and soluble forms of CD163. AB - Three main monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++, differentially regulate tumor growth and survival. Thereby, in the present study we aimed to determine the role of distinct monocyte subsets in the prognostication of chronic lymphocytic leukemia (CLL). Moreover, we set out to analyze the effects of standard immune chemotherapy on different monocyte subsets and levels of membrane-associated and soluble forms of CD163, a monocyte/macrophage-related immunomodulatory protein. We demonstrated that the number of peripheral blood classical CD14++CD16- monocytes assessed at the time of diagnosis was negatively correlated with lymphocytosis and was decreased in the CLL patients who required immediate treatment as opposed to patients who qualified to 'watch and wait' strategy. Notably, lower baseline levels of classical CD14++CD16- monocytes in CLL patients who were qualified for 'watch and wait' therapy were associated with shorter time to initial treatment. Notably, therapy with rituximab, cyclophosphamide and fludarabine resulted in a significant reduction in the number of non-classical CD14+CD16++ monocytes and soluble form of CD163 but upregulation of membrane-associated monocyte CD163. Our data indicate that distinct monocyte subsets and two forms of CD163 are differentially modulated by both CLL and immune chemotherapy. Moreover, we proposed that quantification of classical monocytes at the time of diagnosis contributes to better prognostication of CLL patients. PMID- 26135618 TI - Highly thermostable, flexible, and conductive films prepared from cellulose, graphite, and polypyrrole nanoparticles. AB - In this study, graphite powder (GP) was introduced into the conductive cellulose/polypyrrole (PPy) composite films to increase their conductivity and thermal stability. The GP was dispersed in ionic liquid 1-butyl-3 methylimidazolium chloride ([Bmim]Cl) before the dissolution of cellulose, and the cellulose/GP/PPy films were prepared by in situ chemical polymerization of PPy nanoparticles on the film surface. The structural characteristics and properties of the composite films were investigated in detail. The GP flakes, which were embedded in the cellulose matrix, increased the thickness and decreased the density of the films, leading to the decrement of mechanical properties. However, the thermal stability of the films was significantly improved by the incorporation of graphite, and the composite film could even substantially maintain the original shape after being burned. In addition, the electrical conductivity of the films was increased seven times, leading to the excellent electromagnetic interference shielding effectiveness. The cellulose/GP/PPy film could be considered as a potential candidate for the effective lightweight electromagnetic interference shielding materials in electronics, radar evasion, aerospace, and other applications. PMID- 26135619 TI - Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma. AB - Epstein-Barr virus (EBV), aetiologically linked to nasopharyngeal carcinoma (NPC), is the first human virus found to encode many miRNAs. However, how these viral miRNAs precisely regulate the tumour metastasis in NPC remains obscure. Here we report that EBV-miR-BART1 is highly expressed in NPC and closely associated with pathological and advanced clinical stages of NPC. Alteration of EBV-miR-BART1 expression results in an increase in migration and invasion of NPC cells in vitro and causes tumour metastasis in vivo. Mechanistically, EBV-miR BART1 directly targets the cellular tumour suppressor PTEN. Reduction of PTEN dosage by EBV-miR-BART1 activates PTEN-dependent pathways including PI3K-Akt, FAK p130(Cas) and Shc-MAPK/ERK1/2 signalling, drives EMT, and consequently increases migration, invasion and metastasis of NPC cells. Reconstitution of PTEN rescues all phenotypes generated by EBV-miR-BART1, highlighting the role of PTEN in EBV miR-BART-driven metastasis in NPC. Our findings provide new insights into the metastasis of NPC regulated by EBV and advocate for developing clinical intervention strategies against NPC. PMID- 26135621 TI - Molecular aspects of melatonin (MLT)-mediated therapeutic effects. AB - Hormones are a class of molecules, which mediate their effects by regulating a variety of signalling pathways. Melatonin (N-acetyl-5-methoxytryptamine), a pineal gland hormone, is one among the categories of compounds having various therapeutic and pharmacological effects. Melatonin has many intracellular as well as extracellular targets including apoptosis, metastasis, angiogenesis and inflammatory pathways. Gene-profile studies have further established its antagonist effect on the various genes involved in the tumour progression, neurodegeneration and ageing. It has also been known to reduce the toxicity induced by chemotherapeutic agents in advanced stages of tumour. The present review extensively describes the molecular interactions of melatonin with various recognized cellular targets, which may lead the scientific community to propose novel therapeutic strategies. PMID- 26135620 TI - A germline mutation in SRRM2, a splicing factor gene, is implicated in papillary thyroid carcinoma predisposition. AB - Papillary thyroid carcinoma (PTC) displays strong but so far largely uncharacterized heritability. Here we studied genetic predisposition in a family with six affected individuals. We genotyped all available family members and conducted whole exome sequencing of blood DNA from two affected individuals. Haplotype analysis and other genetic criteria narrowed our list of candidates to a germline variant in the serine/arginine repetitive matrix 2 gene (SRRM2). This heterozygous variant, c.1037C > T (Ser346Phe or S346F; rs149019598) cosegregated with PTC in the family. It was not found in 138 other PTC families. It was found in 7/1,170 sporadic PTC cases and in 0/1,404 controls (p = 0.004). The encoded protein SRRM2 (also called SRm300) is part of the RNA splicing machinery. To evaluate the possibility that the S346F missense mutation affects alternative splicing, we compared RNA-Seq data in leukocytes from three mutation carriers and three controls. Significant differences in alternative splicing were identified for 1,642 exons, of which a subset of 7 exons was verified experimentally. The results confirmed a higher ratio of inclusion of exons in mutation carriers. These data suggest that the S346F mutation in SRRM2 predisposes to PTC by affecting alternative splicing of unidentified downstream target genes. PMID- 26135622 TI - Effect of chronic kidney disease on macrophage cholesterol efflux. AB - AIMS: Patients with chronic kidney disease (CKD) have a high risk to develop atherosclerosis. The capacity of high-density lipoproteins (HDL) or serum to accept cholesterol from macrophages and the capacity of macrophages to export excess cholesterol are critical for the atheroprotective role of reverse cholesterol transport. HDL cholesterol acceptor capacity was reported to be decreased in middle aged hemodialysis patients, but the role of confounding factors remains unclear. MAIN METHODS: We measured the cholesterol acceptor capacity (CAC) of HDL or serum in 12 pediatric and 17 young adult patients with CKD stages 3-5, 14 young adult hemodialysis patients and 15 adult renal transplant recipients without associated diseases and matched controls using THP 1 macrophages. Moreover we studied the cholesterol export capacity (CEC) of patients' monocyte-derived macrophages (HMDMs) to control serum or HDL. KEY FINDINGS: In adults with CKD stages 3-5 serum CAC was slightly increased, whereas CEC of HMDMs was unaltered in both, adult and pediatric patients. In hemodialysis patients, however, serum CAC was markedly reduced to 85+/-11% of control (p<0.001), presumably due to low serum apolipoprotein A-I. Interestingly, CEC of HMDMs from dialysis patients was increased. In transplant patients no alterations were found. SIGNIFICANCE: CKD without hemodialysis does not reduce cholesterol export from macrophages. Hemodialysis patients might benefit from therapies aiming to restore serum CAC by increasing apolipoprotein A-I. The enhanced export of cholesterol by HMDMs from dialysis patients may represent an adaptive response. PMID- 26135623 TI - The influence of caffeine on the activity of moclobemide, venlafaxine, bupropion and milnacipran in the forced swim test in mice. AB - AIMS: Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. It is thus possible to demonstrate the usefulness of caffeine and its derivatives in the treatment of depression. The main goal of the present studywas to evaluate the influence of caffeine (5mg/kg) on the activity of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg), bupropion (10 mg/kg), and milnacipran (1.25 mg/kg). Moreover, we assessed the influence of caffeine on their serum and brain levels using highperformance liquid chromatography. MAIN METHODS: The experiment was carried out on naive adult male Albino Swiss mice. Caffeine and tested drugs were administered intraperitoneally. The influence of caffeine on the activity of selected antidepressant drugs was evaluated in forced swim test (FST). Locomotor activity was estimated to verify and exclude false positive/negative results. To assess the influence of caffeine on the levels of studied antidepressant drugs, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. KEY FINDINGS: Caffeine potentiated activity of all antidepressants examined in FST and the observed effects were not due to the increase in locomotor activity in the animals. Only in the case of co administration of caffeine and milnacipran an increased milnacipran concentration in serum was observed without affecting its concentration in the brain. SIGNIFICANCE: Caffeine potentiates the activity of antidepressant drugs from different chemical groups. The interactions of caffeine with venlafaxine, bupropion and moclobemide occur in pharmacodynamic phase, whereas the interaction of caffeine-milnacipran occurs, at least partially, in pharmacokinetic phase. PMID- 26135624 TI - Exercise modulates liver cellular and mitochondrial proteins related to quality control signaling. AB - AIMS: The effects of exercise on cardiac and skeletal muscle, including the increase on mitochondrial function, dynamics, biogenesis and autophagy signaling are well described. However, these same effects on liver mitochondria, important in the context of hepatocyte ability to mitigate drug-induced injury and obesity related disorders, are not fully understood. Therefore, the effects of two distinct chronic exercise models (endurance training--ET and voluntary physical activity--VPA) on liver cellular and mitochondrial quality control were analyzed. MAIN METHODS: Eighteen male-adult Sprague-Dawley rats were divided into sedentary (SED), ET (12-week treadmill) and VPA (12-week voluntary free wheel). Liver mitochondrial alterations were evaluated by semi-quantification of proteins involved in oxidative stress (SIRT3, p66shc, p66(Ser36)), biogenesis (citrate synthase, PGC-1alpha and mtTFA), dynamics (MFN1, OPA1 and DRP1) and auto(mito)phagy (Beclin-1, Bcl-2, LC3II/LC3I, p62, Parkin and PINK) signaling. Liver ultrastructural alterations were also evaluated. KEY FINDINGS: Both exercise models induced beneficial alterations on liver mitochondrial morphology and increased mitochondrial biogenesis (PGC-1alpha and mtTFA), autophagy-related proteins (Beclin-1, LC3-II, LC3II/LC3I), and DRP1 and SIRT3 proteins. Increased citrate synthase activity and OPA1, p62 and Parkin content as well as decreased PINK protein levels were only observed after ET. VPA decreased OPA1, Beclin-1/Bcl 2, Parkin and p66(Ser36). Mitochondrial density and circularity increased in both exercised groups. SIGNIFICANCE: Both chronic exercise models increased proteins related with mitochondrial biogenesis and alteration proteins involved in mitochondrial dynamics and autophagy signaling, suggesting that exercise can induce liver mitochondrial adaptive remodeling and hepatocyte renewal. PMID- 26135625 TI - Salvianolic acid A inhibits endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats. AB - AIMS: Despite the numerous pharmacological agents available for hypertension therapy, hypertension-related microvascular remodeling is not resolved, eventually leading to end-organ damage. The aim of the present study was to investigate the protection of salvianolic acid A (SalA) against microvascular remodeling in vitro and in vivo. MAIN METHODS: Spontaneously hypertensive rats (SHRs) were administered 2.5, 5 or 10 mg/kg SalA via intraperitoneal injection once a day for 4 weeks. The tail-cuff method was applied to monitor blood pressure; the microvascular structure of the retina was detected by hematoxylin eosin and immunohistochemical staining; the function of mesenteric arteries was measured by DMT wire myography; endothelial cell proliferation was estimated using the Cell Counting Kit-8; endothelial cell migration was evaluated by wound healing and transwell assay; and endothelial cell integrity was detected by transendothelial electrical resistance and permeability assays. KEY FINDINGS: Although no antihypertensive effects of SalA were observed, SalA attenuated the microvascular inward remodeling of the retina and improved microvascular function in the mesenteries in vivo. Further cell experiments confirmed the beneficial effects of SalA on the integrity of the endothelial monolayer in vitro. SIGNIFICANCE: Salvianolic acid A inhibited endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats. Therefore, salvianolic acid A could be a potential drug therapy to prevent further targeted organ damage induced by vascular remodeling. PMID- 26135626 TI - Paclitaxel pretreatment overcomes hypoxia inducible factor-1alpha-induced radioresistance acquisition of human hepatoma and lung adenocarcinoma cells. AB - AIMS: This study delineated the mechanisms of paclitaxel (PTX) assistance in overcoming radioresistance in hepatoma and human lung adenocarcinoma (HLAC) cells. MAIN METHODS: The TUNEL assay was used as an index of radiosensitivity, and the MTT assay assessed the efficacy of various combined PTX/RT treatments. The efficacy of PTX disruptions of hypoxia-inducible factor-1 alpha (HIF-1alpha) was assessed using Western blotting. KEY FINDINGS: Normoxically overexpressed HIF 1alpha in hepatoma J5 cells was mechanistically linked to activation of the bFGF/PI3K/Akt pathway because the viability of these cells was strongly inhibited by either Akt inhibitors or an HIF-1alpha inhibitor. All of the cell lines used were extremely sensitive to PTX, and these effects also correlated excellently with HIF-1alpha suppression. We designed five combined radiation-PTX protocols of varying dose duration and treatment sequences against CL1-1 cells based on the gathered data. Pretreatment of CL1-1 cells with PTX (100nM) for 24h before irradiation (2.5Gy) was the best combined protocol to achieve maximum radiosensitizing effects. SIGNIFICANCE: Our data clearly indicate that PTX pretreatment is an effective radiosensitizing procedure against HIF-1alpha expressing hepatoma and HLAC cells, which are constitutively endowed with radioresistance. PMID- 26135627 TI - Acute restraint stress reduces hippocampal oxidative damage and behavior in rats: Effect of S-allyl cysteine. AB - AIMS: This simple study was designed to investigate whether acute restraint stress can generate changes in behavioral tests and hippocampal endpoints of oxidative stress in rats, and if the antioxidant S-allyl cysteine (SAC) can prevent these alterations. MATERIALS AND METHODS: We evaluated motor activity, forced swimming and anxiety behavior, as well as the hippocampal levels of lipid peroxidation and the activities of glutathione-related enzymes in animals submitted to mild immobilization. The effect of SAC (100 mg/kg, i.p.), given to rats every day 30 min before starting the immobilization session, was also investigated. Immobilization (restraint) stress was induced for a period of 6 h per day for five consecutive days. KEY FINDINGS: Our results indicate that, under the tested conditions, acute restraint stimulates compensatory behavioral tasks (motor activity, anxiety and forced swimming) to counteract the stressing conditions prevailing, and selectively increased the levels of lipid peroxidation and the enzyme activities of glutathione-S-transferase (GST) and glutathione peroxidase (GPx) in the hippocampus also as adaptive responses. SAC exhibited preventive effects in the stressed group as it improved behavior, reduced lipid peroxidation and prevented the increase of GST and GPx activities, suggesting that this antioxidant blunted primary pro-oxidative stimuli induced by restraint stress. SIGNIFICANCE: Findings of this work also confirm that the use of antioxidants such as SAC can provide effective protection against the acute oxidative damage associated with anxiety produced by stressing conditions. PMID- 26135629 TI - Bioinformatics analysis to identify the differentially expressed genes of glaucoma. AB - The aim of the present study was to screen the differentially expressed genes (DEGs) associated with glaucoma and investigate the changing patterns of the expression of these genes. The GSE2378 gene microarray data of glaucoma was downloaded from the Gene Expression Omnibus database, which included seven normal samples and eight glaucoma astrocyte samples. Taking into account the corresponding associations between the probe ID and gene symbols, the DEGs were identified prior to and subsequent to the summation of probe level values using the Limma package in R language, followed by Gene Ontology (GO) and pathway enrichment analyses. Interaction networks of the DEGs were constructed using the Biomolecular Interaction Network Database, and cluster analysis of the genes in the networks was performed using ClusterONE. Subsequent to the summation of probe value, a total of 223 genes were identified as DEGs between the normal and glaucoma samples, including 74 downregulated and 149 upregulated genes. In addition, the DEGs were found to be associated with several functions, including response to wounding, extracellular region part and calcium ion binding. The most significantly enriched pathways were complement and coagulation cascades, arrhythmogenic right ventricular cardiomyopathy and extracellular matrix (ECM) receptor interaction. Furthermore, interaction networks were constructed of the DEGs prior to and subsequent to the summation of probe values, and HNF4A and CEBPD were identified as hub genes. Additionally, 37 and 31 GO terms were identified to be enriched in the two DEGs of the networks prior to and subsequent to summation, respectively. The results indicated the identified genes associated with ECM as important, and the CEBPD gene was considered to be a critical gene in glaucoma. The findings of the present study offer a potential reference value in further investigations of glaucoma at the gene level. PMID- 26135630 TI - Early pregnancy exposure to selective serotonin reuptake inhibitors, risks of major structural malformations, and hypothesized teratogenic mechanisms. AB - INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to manage antenatal depression. Hence, the aim of this systematic review is to assess the prevalence of birth defects associated with pregnancy exposure to such agents and summarize the hypothesized teratogenic mechanisms. AREAS COVERED: Medical literature published in English (1980 - June 2015) was electronically searched to identify all articles reporting an increased prevalence of birth defects associated with prenatal SSRI exposure and hypothesizing teratogenic mechanisms. EXPERT OPINION: The only recurrent pattern of congenital anomalies associated with antenatal SSRI exposure is heart defects. SSRIs may alter the function of serotonin and related receptors which are involved in the development of the monoamine-dependent cardiac structures. Nevertheless, the magnitude of this increase and, thus, its clinical significance are unclear. Therefore, a cautious approach of using SSRI during pregnancy only in the case of major depressive episodes should be applied. However, this risk should be balanced against the risks associated with the worsening of depressive symptoms, and take into consideration the large number of studies that found no associations between transplacental SSRI exposure and cardiac anomalies. Prenatal ultrasonography and Doppler sonography to detect early cardiac defects are also advisable. Non pharmacological approaches are preferred for less severe psychiatric disorders. PMID- 26135631 TI - Cantharidin represses invasion of pancreatic cancer cells through accelerated degradation of MMP2 mRNA. AB - Cantharidin is an active constituent of mylabris, a traditional Chinese medicine, and is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays an important role in cell cycle control, apoptosis, and cell-fate determination. In the present study, we found that cantharidin repressed the invasive ability of pancreatic cancer cells and downregulated matrix metalloproteinase 2 (MMP2) expression through multiple pathways, including ERK, JNK, PKC, NF-kappaB, and beta-catenin. Interestingly, transcriptional activity of the MMP2 promoter increased after treatment with PP2A inhibitors, suggesting the involvement of a posttranscriptional mechanism. By using an mRNA stability assay, we found accelerated degradation of MMP2 mRNA after treatment of cantharidin. Microarray analyses revealed that multiple genes involved in the 3' -> 5' decay pathway were upregulated, especially genes participating in cytoplasmic deadenylation. The elevation of these genes were further demonstrated to be executed through ERK, JNK, PKC, NF-kappaB, and beta-catenin pathways. Knockdown of PARN, RHAU, and CNOT7, three critical members involved in cytoplasmic deadenylation, attenuated the downregulation of MMP2. Hence, we present the mechanism of repressed invasion by cantharidin and other PP2A inhibitors through increased degradation of MMP2 mRNA by elevated cytoplasmic deadenylation. PMID- 26135633 TI - Pneumococcal vaccination and Streptococcus pneumoniae serotypes. PMID- 26135632 TI - Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease. AB - Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the alpha-galactosidase A (alpha-Gal A) lysosomal enzyme, which results in globotriaosylceramide (Gb3) storage in vascular endothelial cells and different cell types throughout the body. Involvement of the kidney and heart is life threatening, and fibrosis of these organs is considered to be involved in the pathogenesis of Fabry disease. An increased concentration of deacylated Gb3 (lyso-Gb3) in the plasma of symptomatic patients has also been suggested as a causative molecular event. To elucidate the molecular mechanisms involved in renal fibrosis in Fabry disease, the present analyzed the changes in global gene expression prior to and following Gb3 or lyso-Gb3 treatment in two types of kidney cell lines, human proximal renal tubular epithelial (HK-2) and mouse renal glomerular mesangial (SV40 MES 13) cells. Gb3 and lyso-Gb3 treatment regulated the expression of 199 and 328 genes in each cell type, demonstrating a >2.0-fold change. The majority of the biological functions of the regulated genes were associated with fibrogenesis or epithelial-mesenchymal transition (EMT). The gene expression patterns of sphingolipid-treated HK-2 cells were distinguishable from the patterns in the SV40 MES 13 cells. Several genes associated with the EMT were selected and evaluated further in kidney cells and in Fabry mouse kidney tissues. In the SV40 MES 13 cells, the DLL1, F8, and HOXA11 genes were downregulated, and FOXP2 was upregulated by treatment with Gb3 or lyso-Gb3. In the HK-2 cells, the ADAMTS6, BEST1, IL4, and MYH11 genes were upregulated. Upregulation of the FOXP2, COL15A1, IL4, and MYH11 genes was also observed in the Fabry mouse kidney tissues. The gene expression profiles in kidney cells following the addition of Gb3 or lyso-Gb3 revealed substrate-specific and cell-specific patterns. These findings suggested that Gb3 and lyso-Gb3 lead to renal fibrosis in Fabry disease through different biochemical modulations. PMID- 26135634 TI - Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease. AB - Atherosclerotic cardiovascular disease (ACD) is the leading cause of mortality worldwide. The objective of this paper is to provide an overview of the global burden of ACD and its risk factors and to discuss the main challenges and opportunities for prevention. Publicly available data from the Global Burden of Disease Study were analyzed for ischemic heart disease (IHD), ischemic stroke and ACD risk factors. Data from the WHO Global Health Observatory were used to describe prevalence of diverse cardiometabolic risk factors. World Bank Gross Domestic Product per capita (GDPc) information was used to categorize countries according to income level. Cardiovascular mortality decreased globally from 1990 2010 with important differences by GDPc; during 1990 there was a positive association between IHD mortality and GDPc. Higher-income countries had higher rates compared to those of lower-income countries. High levels of body mass index (BMI), blood pressure, glucose and cholesterol have a differential contribution to mortality by income group over time; high-income countries have been able to reduce the contribution from these risk factors in the last 20 years, whereas lower/middle income countries show an increasing trend in mortality attributable to high BMI and glucose. Although age-adjusted ACD mortality rate trends decreased globally, the absolute number of ACD deaths is increasing in part due to the growth of the population and aging, as well as to important lifestyle and food-system changes that likely attenuate gains in prevention. Population and individual level preventable causes of ACD must be aggressively and efficiently targeted in countries of lower economic development in order to reduce the growing burden of disease due to ACD. PMID- 26135635 TI - Magnetic evolution and anomalous Wilson transition in diagonal phosphorene nanoribbons driven by strain. AB - Inducing magnetism in phosphorene nanoribbons (PNRs) is critical for practical applications. However, edge reconstruction and Peierls distortion prevent PNRs from becoming highly magnetized. Using first-principles calculations, we find that relaxed oxygen-saturated diagonal-PNRs (O-d-PNRs) realize stable spin polarized antiferromagnetic (AFM) coupling, and the magnetism is entirely localized at the saturated edges. The AFM state is quite stable under expansive and limited compressive strain. More importantly, not only does the irreversible Wilson transition occur when applying strain, but the nonmagnetic (NM) metal phase (a new ground state) becomes more stable than the AFM state when the compressive strain exceeds -4%. The related stability and transition mechanism are demonstrated by dual tuning of the geometric and electronic structures, which manifests as a geometric deviation from a honeycomb to an orthorhombic-like structure and formation of P-py bonding (P-pz nonbonding) from P-pz nonbonding (P py antibonding) because of the increase of the proportion of the P-py (P-pz) orbital. PMID- 26135636 TI - Tunable continuous wave emission via phase-matched second harmonic generation in a ZnSe microcylindrical resonator. AB - Whispering gallery mode microresonators made from crystalline materials are of great interest for studies of low threshold nonlinear phenomena. Compared to amorphous materials, crystalline structures often exhibit desirable properties such as high indices of refraction, high nonlinearities, and large windows of transparency, making them ideal for use in frequency comb generation, microlasing and all-optical processing. In particular, crystalline materials can also possess a non-centrosymmetric structure which gives rise to the second order nonlinearity, necessary for three photon processes such as frequency doubling and parametric down-conversion. Here we report a novel route to fabricating crystalline zinc selenide microcylindrical resonators from our semiconductor fibre platform and demonstrate their use for tunable, low power continuous wave second harmonic generation. Visible red light is observed when pumped with a telecommunications band source by a process that is phase-matched between different higher order radial modes, possible due to the good spatial overlap between the pump and signal in the small volume resonator. By exploiting the geometrical flexibility offered by the fibre platform together with the ultra wide 500-22000 nm transmission window of the ZnSe material, we expect these resonators to find use in applications ranging from spectroscopy to quantum information systems. PMID- 26135637 TI - Multidimensional Helical Nanostructures in Multiscale Nanochannels. AB - We have investigated the various morphological changes of helical nanofilament (HNF; B4) phases in multiscale nanochannels made of porous anodic aluminum oxide (AAO) film. Single or multihelical structures could be manipulated depending on the AAO pore size and the higher-temperature phase of each molecule. Furthermore, the nanostructures of HNFs affected by the chemical affinity between the molecule and surface were drastically controlled in surface-modified nanochannels. These well-controlled hierarchical helical structures that have multidimensions can be a promising tool for the manipulation of chiral pores or the nonlinear optical applications. PMID- 26135638 TI - Optical coherence tomographic angiography of choroidal neovascularization associated with central serous chorioretinopathy. PMID- 26135639 TI - A Terminal N2 Complex of High-Spin Iron(I) in a Weak, Trigonal Ligand Field. AB - The role of Fe in biological and industrial N2 fixation has inspired the intense study of small molecule analogues of Fe-(NxHy) intermediates of potential relevance to these processes. Although a number of low-coordinate Fe-(N2) featuring varying degrees of fidelity to the nitrogenase active site are now known, these complexes frequently feature strongly donating ligands that either enforce low- or intermediate-spin states or result in linear Fe-(N2)-Fe bridging motifs. Given that the nitrogenase active site uses weak-field sulfide ligands to stabilize its reactive Fe center(s), N2 binding to high-spin Fe is of great interest. Herein, we report the synthesis and characterization of the first terminal N2 complex of high-spin (S = 3/2) Fe(I) as well as a bridging Fe-(N2)-Fe analogue. Electron paramagnetic resonance and solution magnetic moment determination confirm the high-spin state, and vibrational experiments indicate a substantial degree of activation of the N=N bond in these complexes. Density functional theory calculations reveal an electronic structure for the terminal adduct featuring substantial delocalization of unpaired spin onto the N2 ligand. PMID- 26135640 TI - Sexual maturation and changes in water and salt transport components in the kidney and intestine of three-spined stickleback (Gasterosteus aculeatus L.). AB - Mature three-spined stickleback males use spiggin threads secreted from their kidney to glue together nest material. This requires strongly hypertrophied renal proximal tubular cells, which compromises renal osmoregulatory function during the breeding period. Experimental evidence suggests that the intestine takes over hypotonic fluid secretion at that stage but the mechanism is unexplored. To unravel the molecular mechanism we analyzed and compared transcript levels of several membrane proteins involved in water and salt transport in intestinal and renal tissues, in non-mature males (NM), mature males (MM), and mature females (MF). Aquaporin paralogs aqp1a, -3a, -8aa, -8ab, -10a, and -10b, two Na(+),K(+) ATPase alpha-1 subunit isoforms (nka547, nka976), Na(+),K(+),2Cl(-)-, and Na(+),Cl(-)-cotransporters (nkcc1a, nkcc2, ncc), the cystic fibrosis transmembrane conductance regulator (cftr) and two claudin isoforms (cldn2, cldn15a) were expressed in the intestine and kidney in all groups. There were no differences in aqp and cldn expression between intestines of NM and MM; nkcc2 was lower and nka levels tended to be higher in intestines of MM than in NM. In the kidney, aqp1 and aqp8ab levels were lower in MM than in NM, whereas aqp3a, nkcc1a, cldn15a, and spiggin were markedly elevated. This was accompanied by marked hypertrophy of kidney tubules in MM. The data support an altered kidney function in terms of water handling in mature males, whereas there was no support for modified trans-epithelial water permeability or salt-secretory activity in the intestine of mature males. Salt-absorptive activity in the intestine may, however, be down-regulated during male maturation. PMID- 26135641 TI - Evaluation of a field appropriate membrane filtration method for the detection of Vibrio cholerae for the measurement of biosand filter performance in the Artibonite Valley, Haiti. AB - Biosand filters in the Artibonite Valley of Haiti, the epicenter of the cholera epidemic that began in October 2010, were tested for total coliform and Vibrio cholerae removal efficiencies. While coliform are often used as an indicator organism for pathogenic bacteria, a correlation has never been established linking the concentration of coliform and V. cholerae, the causative agent for cholera. Hence, a method for field enumeration of V. cholerae was developed and tested. To this end, a plate count test utilizing membrane filtration technique was developed to measure viable V. cholerae cell concentration in the field. Method accuracy was confirmed by comparing plate count concentrations to microscopic counts. Additionally, biosand filters were sampled and removal efficiencies of V. cholerae and coliform bacteria compared. The correlation between removal efficiency and time in operation, biofilm ("schmutzdecke") composition, and idle time was also investigated. The plate count method for V. cholerae was found to accurately reflect microscope counts and was shown to be effective in the field. Overall, coliform concentration was not an appropriate indicator of V. cholerae concentration. In 90% of the influent samples from the study, coliform underestimated V. cholerae concentration (n = 26). Furthermore, coliform removal efficiency was higher than for V. cholerae hence providing a conservative measurement. Finally, time in operation and idle time were found to be important parameters controlling performance. Overall, this method shows promise for field applications and should be expanded to additional studies to confirm its efficacy to test for V. cholerae in various source waters. PMID- 26135642 TI - Toxicological relevance of endocrine disruptors in the Tagus River estuary (Lisbon, Portugal). AB - The Tagus is the longest Iberian river, notwithstanding, the levels of natural and xenoestrogenic endocrine-disrupting compounds (EDCs) were never measured in its estuary. Suspecting for their presence, we made a major survey of 17 EDCs that include: (i) natural (17beta-oestradiol and estrone) and pharmaceutical oestrogens (17alpha-ethynylestradiol); (ii) industrial and household pollutants (octylphenols, nonylphenols and their mono and diethoxylates, and bisphenol A); (iii) phytoestrogens (biochanin A, daidzein, formononetin, genistein); and (iv) the phytosterol (sitosterol). Water samples from the Tagus estuary were taken from nine locations every 2 months over a 1-year period and analysed by gas chromatography. Oestrogens, industrial/household pollutants were consistently higher at two sites-at Tagus River mouth and close to the Trancao tributary, both at Lisbon region. The overall oestrogenic load, in ethynylestradiol equivalents, was 13 ng/L for oestrogens, 2.3 ng/L for industrial/household pollutants and 43 ng/L for phytoestrogens; well in the range of toxicological significance. Water physicochemical parameters also indicated anthropogenic pollution, mainly at the two above-referred sampling sites. PMID- 26135643 TI - Imaging of childhood inflammatory myofibroblastic tumor. AB - BACKGROUND: Inflammatory myofibroblastic tumor is a rare benign neoplasm and most commonly involves the lung but occurs in extrapulmonary locations. OBJECTIVE: To present imaging findings in inflammatory myofibroblastic tumors in children based on a single-centre experience. MATERIALS AND METHODS: We retrospectively reviewed CT and MRI findings of children diagnosed with inflammatory myofibroblastic tumor in a single institution. RESULTS: We identified 15 children (range: 1-17 years) with inflammatory myofibroblastic tumor. The tumor was localized to the lung (n = 5), mediastinum (n = 3), trachea (n = 1), bronchus (n = 1), abdomen (n = 2) and orbit (n = 3). All the extraorbital tumors were solid masses with homogeneous or heterogeneous enhancement. Four lung tumors and one posterior mediastinal tumor contained calcification. Local recurrence following surgical removal occurred in two children with invasion of the esophagus and of the left atrium in one. Localized masses were seen in all children with orbital tumour. Two of these had episcleritis and perineuritis; one had episcleritis, tendonitis, perineuritis, myositis and dacryoadenitis. CONCLUSION: The locations and imaging features of inflammatory myofibroblastic tumors are variable. PMID- 26135644 TI - Madelung deformity and Madelung-type deformities: a review of the clinical and radiological characteristics. AB - Madelung deformity of the distal radius results from premature closure of the medial volar aspect of the distal radial physis, leading to increased volar tilt and increased inclination of the radial articular surface, triangulation of the carpus with proximal migration of the lunate and dorsal displacement of the distal ulna. The deformity is particularly common in Leri-Weill dyschondrosteosis, but it may also occur in isolation. True Madelung deformity can be differentiated from Madelung-type deformities by the presence of an anomalous radiolunate ligament (Vickers ligament). In this article, we will review the imaging characteristics of true Madelung deformity, including the common "distal radius" variant, the less common "entire radius" variant and "reverse" Madelung deformity. We will discuss the role of the Vickers ligament in disease pathogenesis and its use in differentiating true Madelung deformity from Madelung-type deformities arising from trauma or multiple hereditary exostoses. Surgical management of these patients will also be addressed. PMID- 26135645 TI - Silicon nanostructures for cancer diagnosis and therapy. AB - The emergence of nanotechnology suggests new and exciting opportunities for early diagnosis and therapy of cancer. During the recent years, silicon-based nanomaterials featuring unique properties have received great attention, showing high promise for myriad biological and biomedical applications. In this review, we will particularly summarize latest representative achievements on the development of silicon nanostructures as a powerful platform for cancer early diagnosis and therapy. First, we introduce the silicon nanomaterial-based biosensors for detecting cancer markers (e.g., proteins, tumor-suppressor genes and telomerase activity, among others) with high sensitivity and selectivity under molecular level. Then, we summarize in vitro and in vivo applications of silicon nanostructures as efficient nanoagents for cancer therapy. Finally, we discuss the future perspective of silicon nanostructures for cancer diagnosis and therapy. PMID- 26135646 TI - Protonation effect on ligands in EuL: a luminescent switcher for fast naked-eye detection of HCl. AB - A new luminescent coordination polymer, EuH(L)(2)(NO(3))(2) (EuL, HL = 2-(2 pyridin-2-yl)quinoline-4-carboxylic acid), has been solvothermally synthesized, and its framework of uncoordinated pyridyl rings was exploited for the binding and specific sensing of HCl via a protonation effect. The protonation effect changes the energy of the excited state of the ligands, rendering them unable to act as efficient antennae for Eu(3+) characteristic emission. Thus, we have developed a new, fast and convenient sensor for HCl, a gas harmful for the environment. PMID- 26135647 TI - Prevalence of esophageal squamous papilloma (ESP) and associated cancer in northeastern France. AB - BACKGROUND AND STUDY AIMS: Esophageal squamous papilloma (ESP) is a rare lesion. The aims of this study were to assess the prevalence of ESP in northeastern France and the risk of associated squamous cell carcinoma (SCC). PATIENTS AND METHODS: The charts of 78 patients who were diagnosed with ESP between January 2005 and February 2013 at three hospitals in northeastern France were reviewed. RESULTS: A total of 55 305 endoscopies were performed and 78 ESP were diagnosed (0.01 %). Patients with ESP included 44 males (56.4 %), 34 females (43.6 %); median age 50, interquartile range (IQR) 19 - 86. Median follow-up was 21 months (IQR 0 - 91 mo) and median time between first and second endoscopy was 7 months (IQR 0.5 - 74 mo). Of the total number of patients, 35 (44.9 %) had a second endoscopy. Main endoscopy indication was dyspepsia (24.4 %). Most ESP were isolated (93.6 %) and located at distal esophagus (27 cm, IQR 16 - 40 cm). Median size was 3 mm (IQR 1 - 20 mm). ESP-associated endoscopic lesions were hiatal hernia in 12 patients and esophagitis in 11 patients. Endoscopic treatment was mainly excisional biopsies (60.3 %). Human papillomavirus (HPV) was not detected in the 6 patients with available data. Low dysplasia was found in 2 ESP. During follow-up endoscopies, 2 SCC were detected in 2 different patients; the first SCC was located at the previous resection site of the ESP and the second had a different location. Prevalence of associated cancer was 1.3 %. CONCLUSION: Prevalence of ESP in northeastern France is similar to that previously reported. Endoscopic findings were also broadly the same as in previous reports. The occurrence of dysplasia and SCC should strongly encourage the endoscopist to totally remove the ESP and to start an endoscopic surveillance, given the potential risk of malignant transformation. PMID- 26135648 TI - Cryospray ablation using pressurized CO2 for ablation of Barrett's esophagus with early neoplasia: early termination of a prospective series. AB - BACKGROUND: Cryotherapy is a relatively novel ablation modality for the endoscopic ablation of Barrett's esophagus (BE). Data on the use of pressurized carbon dioxide (CO2) gas for cryoablation are scarce. STUDY AIM: To determine the efficacy and safety of cryospray ablation using pressurized CO2 gas in the treatment of BE with early neoplasia. METHODS: In this prospective single center case series, we aimed to include 30 patients with BE and early neoplasia. Nodular neoplastic lesions were treated with endoscopic mucosal resection (EMR). Residual BE mucosa was treated with cryospray ablation every 4 weeks until the complete BE segment was eliminated or up to seven treatment sessions. If no reduction of the BE segment was observed after two subsequent treatment sessions, cryoablation was terminated. Patients were contacted at days 1 and 4 post-treatment to evaluate the level of discomfort. Endoscopic and histologic follow-up evaluations were performed up to 24 months post-treatment. RESULTS: After the inclusion of 10 patients, insufficient effect of cryoablation was observed, resulting in early termination of the study. In total, seven patients with intramucosal carcinoma (IMC) and three with high grade dysplasia (HGD) were included. Prior EMR was performed in nine patients. A median of 2.5 (IQR 2.0 - 4.0) cryoablation sessions were performed. At 6 months of follow-up, complete eradication of intestinal metaplasia was observed in 11 % (1 /9; one patient died, not treatment or disease related) of the patients and complete eradication of dysplasia in 44 % (4 /9). In three patients, HGD or IMC was detected during follow-up, and was endoscopically treated. Apart from a gastric perforation as a result of gastric distension caused by CO2 gas during the first treatment, cryospray treatments were well tolerated. CONCLUSION: After a short learning curve, cryoablation using CO2 gas was found to be a safe and well tolerated treatment modality. However, in our experience, the efficacy of CO2 cryoablation combined with EMR for nodular lesions is disappointing for the treatment of BE associated neoplasia. PMID- 26135649 TI - Efficacy of short period, low dose oral prednisolone for the prevention of stricture after circumferential endoscopic submucosal dissection (ESD) for esophageal cancer. AB - BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) was developed in Japan and has been performed on many patients with early stage esophageal cancer; however quality of life in patients with postoperative stricture is drastically decreased and repeat, periodic endoscopic balloon dilatation (EBD) is usually required over long periods. In this study, we evaluate the efficacy of short period, low dose oral prednisolone in controlling post-procedural esophageal stricture. PATIENTS AND METHODS: In total, 33 patients who underwent semicircular or complete circular ESD for esophageal superficial squamous cell carcinoma were included in this study. They were divided into two groups: those who underwent large-circumference ESD with no preventative treatment for stricture (ESD alone group) and those who received systemic steroid treatment for stricture (oral prednisolone group). We compared the two groups in terms of stricture rate and total number of EBD sessions. The ESD alone group underwent no preventative treatment. The oral prednisolone group started with 30 mg/day prednisolone on the second day post-ESD, and continued with a gradually tapering prednisolone dose, finally discontinuing systemic steroid administration 3 weeks later. RESULTS: The stricture rate after ESD was significantly lower in the oral prednisolone group (3 of 17 patients; 17.6 %) than in the ESD alone group (11 of 16 patients; 68.7 %) (P < 0.01). The number of EBD sessions was significantly lower in the oral prednisolone group than in the ESD alone group (median 4.6, range 2 - 10 vs. median 8.1, range 1 - 18; P < 0.01). CONCLUSION: Short period, low dose oral prednisolone showed promising results for the prevention of stricture after ESD for early stage esophageal cancers. PMID- 26135650 TI - Prevention of esophageal stenosis after large endoscopic submucosal dissection: is there a better way to use steroids? PMID- 26135651 TI - The "white globe appearance" (WGA): a novel marker for a correct diagnosis of early gastric cancer by magnifying endoscopy with narrow-band imaging (M-NBI). AB - BACKGROUND AND STUDY AIMS: Although magnifying endoscopy with narrow-band imaging (M-NBI) is useful for the diagnosis of gastric mucosal lesions, differentiating between early cancer (EC) and low grade adenoma (LGA) remains a challenge. During M-NBI examination, we have noted the presence of a small, white lesion with a globular shape underneath cancerous gastric epithelium, and have termed this endoscopic finding the "white globe appearance" (WGA). The aim of this study was to determine whether or not the WGA could be an endoscopic marker for distinguishing EC from LGA. METHODS: We retrospectively analyzed both the M-NBI scans and resected specimens of a total of 111 gastric lesions from 95 consecutive patients. Our main outcome was a difference in the prevalence of the WGA in EC and LGA. RESULTS: The prevalence of the WGA in EC and LGA was 21.5 % (20 /93) and 0 % (0 /18), respectively (P = 0.039). The sensitivity, specificity, positive predictive value, and negative predictive value for differentiating between EC and LGA, according to the presence of the WGA, were 21.5, 100, 100, and 19.8 %, respectively. CONCLUSION: A positive WGA in a suspicious lesion on M NBI would be an adjunct to the M-NBI diagnosis of possible EC because the specificity and positive predictive value of the WGA for differentiating between EC and LGA were extremely high. The WGA could be a novel endoscopic marker for differentiating between EC and LGA. PMID- 26135652 TI - Radiofrequency ablation for treatment of refractory gastric antral vascular ectasia (with video). AB - BACKGROUND AND STUDY AIMS: Gastric antral vascular ectasia (GAVE) is a known cause of gastrointestinal bleeding and chronic iron deficiency anemia. Endoscopic therapy with argon plasma coagulation (APC) is widely used for treatment of GAVE, but most patients continue to require repeated blood transfusions and multiple endoscopic procedures (refractory GAVE). We describe our initial experience regarding safety and efficacy of radiofrequency ablation (RFA) therapy in treating patients with refractory GAVE. PATIENTS AND METHODS: We prospectively enrolled seven patients with refractory GAVE who had multiple prior treatments with APC. These patients were treated with RFA (HALO90 ULTRA Ablation Catheter System; Covidien, GI Solutions, Sunnyvale, CA) at Ertan Digestive Disease Center at our tertiary University Hospital. RESULTS: Seven patients underwent a total of 12 RFA procedures for treatment of refractory GAVE. The median number of RFA procedures was 2 (Range, 1 - 3). Average pre- and post-procedural hemoglobin were 9.3 g/dL and 10.16 g/dL, respectively. Five of seven patients (71 %) were transfusion-free after the RFA treatments while two patients continued to require blood transfusions. There were no complications in this series. CONCLUSION: RFA can be an effective alternative to APC for treatment of GAVE refractory to previous endoscopic therapy. Additional studies are needed to identify which subset of patients will benefit the most with RFA treatment. PMID- 26135653 TI - Radiofrequency ablation therapy - the grave for GAVE (gastric antral vascular ectasia)? PMID- 26135654 TI - A multi-institutional survey on the practice of endoscopic ultrasound (EUS) guided pseudocyst drainage in the Asian EUS group. AB - BACKGROUND: There is a lack of consensus on how endoscopic ultrasound (EUS) guided pseudocyst drainage should be performed. This survey was carried out amongst members of the Asian Endoscopic Ultrasonography Group (AEG) to describe their practices in performing this procedure. METHODS: This was an Asia wide multi-institutional survey amongst members of the Asian EUS group conducted between November and December 2013. The responses to a 19-question survey with regard to the practice of pseudocyst drainage were obtained. RESULTS: In total, 19 endoscopists responded to the questionnaire and the mean (SD) number of procedures performed by each endoscopist was 87.95 (40); 42.2 % believed that prior endoscopic retrograde cholangiopancreatography (ERCP) is required and pancreatic duct stenting is indicated in patients with pancreatic duct disruption; 47.4 % used tapered catheters for track dilation and 42.1 % used the cystotome; 84.1 % would dilate the track up to 8 to 10 mm in size. Metallic stents were used by 10.5 % of the respondents and transcystic catheters were employed by 26.3 %. Those who were more experienced in the procedure tended to use the cystotome more frequently (P = 0.02) and removed the stents in less than 3 months after insertion (P = 0.011). CONCLUSION: This was the first Asia wide survey in the practice of pseudocyst drainage. There were wide variations in practice and randomized studies are urgently needed to establish the best approach for management of this condition. There is also a pressing need for establishment of a consensus for safe practices. PMID- 26135656 TI - Improving the results of pancreatic endoscopic ultrasound-guided fine needle aspiration in daily practice: keep it simple. PMID- 26135655 TI - Specialized clinical cytology may improve the results of EUS (endoscopic ultrasound)-guided fine-needle aspiration (FNA) from pancreatic tumors. AB - BACKGROUND AND STUDY AIMS: A variety of factors (needle type, needle passes, tumor location, cytological assessment, etc.) may influence the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration cytology (EUS FNAC) from pancreatic tumors. Whereas most published studies report a diagnostic accuracy of > 80 % for EUS-FNAC, the results in routine settings are often considerably lower. This retrospective study aimed to define the effect of switching microscopic assessment from a standard pathology department to a highly specialized institute of cytology. PATIENTS AND METHODS: A total of 63 patients underwent EUS-FNAC of solid or semisolid pancreatic masses. Specimens of the first consecutive 20 cases (Phase 1) were assessed by the local department of pathology. Then in Phase 2, involving another 43 subsequent cases, a specialized cytology laboratory examined all aspirates. All EUS-FNACs were performed in the same manner, using a 22-gauge needle. After cytological evaluation, all patients either underwent surgery or were followed up for at least 6 months. RESULTS: Of the tumors, 56 were solid and 7 semisolid; the mean size was 30 mm. Sensitivity (sens.), specificity (spec.), positive predictive value (PPV), and negative predictive value (NPV) of EUS-FNAC were 38.5 % (95 %CI [confidence interval] 13.9 - 68.4 %), 100 % (59.0 - 100 %), 100 % (47.8 - 100 %), and 46.7 % (21.3 - 73.4 %) during Phase 1 versus 91.4 % (95 %CI 76.9 - 98.2 %), 100 % (63.1 - 100 %), 100 % (89.1 - 100 %), and 72.7 % (39.0 - 94.0 %) during Phase 2. CONCLUSION: These results emphasize the considerable impact of a dedicated cytological evaluation on the results of EUS-FNAC. PMID- 26135657 TI - The addition of high magnifying endoscopy improves rates of high confidence optical diagnosis of colorectal polyps. AB - BACKGROUND AND STUDY AIMS: The real-time optical diagnosis of colorectal polyps with high confidence predictions can achieve high levels of accuracy. Increasing the rates of high confidence optical diagnosis can improve the clinical application of real-time optical diagnosis in routine practice. The primary aim of this prospective study was to evaluate whether high magnifying endoscopy improves the rates of high confidence narrow-band imaging (NBI) - based optical diagnosis for differentiating between neoplastic and non-neoplastic colorectal lesions according to the NBI international colorectal endoscopic (NICE) classification. PATIENTS AND METHODS: Consecutive adult patients undergoing colonoscopy with a high magnifying (maximum, * 80) colonoscope between April and August 2012 were recruited. The optical diagnosis for each polyp was evaluated during colonoscopy in two consecutive stages by the same endoscopist, who first used NBI with non-magnifying endoscopy (NBI-NME), then NBI with magnifying endoscopy (NBI-ME). A level of confidence was assigned to each prediction. RESULTS: The analysis included 124 patients (mean age, 56.4 years; male-to-female ratio, 72:52) with 248 polyps smaller than 10 mm. Of the 248 polyps, 210 were 1 to 5 mm in size and 38 were 6 to 9 mm in size; 77 polyps were hyperplastic, 4 were sessile serrated adenomas/polyps, 160 were low grade adenomas, 5 were high grade adenomas, and 2 were deep submucosal invasive carcinomas. The rate of high confidence optical diagnosis when NBI-ME was used was significantly higher than the rate when NBI-NME was used for diminutive (1 - 5 mm) polyps (92.9 % vs 79.5 %, P < 0.001) and for small (6 - 9 mm) polyps (94.7 % vs 84.2 %, P = 0.048). CONCLUSION: High magnifying endoscopy significantly improved the rates of high confidence NBI-based optical diagnosis of diminutive and small colorectal polyps. STUDY REGISTRATION: UMIN 000007608. PMID- 26135658 TI - Tissue shielding with polyglycolic acid sheets and fibrin glue on ulcers induced by endoscopic submucosal dissection in a porcine model. AB - BACKGROUND AND STUDY AIMS: The safety and efficacy of the application of polyglycolic acid (PGA) sheets with fibrin glue to ulcers induced by endoscopic submucosal dissection (ESD) have not been established in the treatment of lesions of the gastrointestinal tract, in which the influence of digestive fluid and peristalsis may affect treatment, and there may also be a risk of infection. The aims of this study were to evaluate the healing process of ESD-induced ulcers in animals treated with the application of a PGA sheet with fibrin glue and to verify experimentally the safety of this treatment procedure. MATERIALS AND METHODS: Gastric ESD was performed in nine pigs under general anesthesia. Two ulcer sites were prepared in each pig; one ulcer was treated by applying a PGA sheet with fibrin glue (treated ulcer site), while the other ulcer was left untreated (control ulcer site). Three pigs were euthanized at week 1, three at week 4, and three at week 8 after ESD, and the ulcer sites were macroscopically and histopathologically evaluated. RESULTS: Of the nine treated ulcer sites, seven ulcer sites, to which a PGA sheet had been applied without exposure to the mucosal fluid, showed no peeling of the sheet despite the influence of peristalsis and gastric acid. Histopathologic examination revealed abundant, newly formed blood vessels in the treated ulcers and good granulation. In the treated ulcers, no excessive inflammation, necrosis, or infection was observed. CONCLUSIONS: Our animal study experimentally demonstrated that this treatment technique can be safely applied to ESD-induced ulcers. PMID- 26135659 TI - Is there a need to shield ulcers after endoscopic submucosal dissection in the gastrointestinal tract? PMID- 26135660 TI - Endoscopic extra-cavitary drainage of pancreatic necrosis with fully covered self expanding metal stents (fcSEMS) and staged lavage with a high-flow water jet system. AB - AIM: To present a novel, less-invasive method of endoscopic drainage (ED) for walled-off pancreatic necrosis (WON).We describe the feasibility, success rate, and complications of combined ED extra-cavitary lavage and debridement of WON using a biliary catheter and high-flow water jet system (water pump). PATIENTS AND METHODS: Endoscopic ultrasound (EUS)-guided drainage was performed with insertion of two 7-Fr, 4-cm double pigtail stents. Subsequently a fully covered self-expanding metal stent (fcSEMS) was placed. The key aspect of the debridement was the insertion of a 5-Fr biliary catheter through or along the fcSEMS into the cavity, with ensuing saline lavage using a high-flow water jet system. The patients were then brought back for repeated, planned endoscopic lavages of the WON. No endoscopic intra-cavitary exploration was performed. RESULTS: A total of 17 patients (15 men, 2 women; mean age 52.6, range 24 - 69; mean American Society of Anesthesiologists [ASA] score of 3) underwent ED of WON with this new method. The mean initial WON diameter was 9.5 cm, range 8 to 26 cm. The total number of ED was 84, range 2 to 13. The mean stenting period was 42.5 days. The mean follow up was 51 days, range 3 to 370. A resolution of the WON was achieved in 14 patients (82.3 %). There were no major complications associated with this method. CONCLUSION: ED of complex WON with fcSEMS followed by repeated endoscopic extra cavitary lavage and debridement using a biliary catheter and high-flow water jet system is a minimally invasive, feasible method with high technical and clinical success and minimal complications. PMID- 26135661 TI - Usefulness of endoscopic ultrasound-guided fine-needle aspiration with a forward viewing and curved linear-array echoendoscope for small gastrointestinal subepithelial lesions. AB - BACKGROUND AND STUDY AIMS: It is difficult to perform endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) of small gastrointestinal (GI) subepithelial lesions (SELs) approximately 10 mm in diameter. This study was undertaken to evaluate the feasibility, safety, and diagnostic ability of EUS-FNA with a forward-viewing and curved linear-array echoendoscope (FVCLA-ES) that has a cap for small SELs. PATIENTS AND METHODS: The study enrolled 8 patients who had small upper GI SELs approximately 10 mm in diameter. To fix the SELs during FNA, a cap device was attached to the scope tip. RESULTS: The mean (standard deviation [SD]) diameter of the SELs was 10.6 mm (2.94). Even small lesions were well targeted for FNA when the FVCLA-ES with a cap device was used. The mean (SD) number of passes was 4.6 (1.59). Adequate samples were obtained from 7 patients (87.5 %) - in 6 (75 %) for cytology and in 4 (50 %) for histologic examination with immunohistochemical (IHC) staining. No complication occurred. Gastrointestinal stromal tumor (GIST) in 2 patients and leiomyoma in 2 patients were definitively diagnosed with IHC staining. CONCLUSIONS: EUS-FNA with an FVCLA ES that has a cap device is feasible and safe. This technique is expected to contribute to histologic diagnosis, even in small SELs. PMID- 26135663 TI - Foreword. PMID- 26135662 TI - Minimum biopsy set for HER2 evaluation in gastric and gastro-esophageal junction cancer. AB - BACKGROUND AND STUDY AIMS: The HER2 status of small endoscopic biopsies is important for predicting the eligibility of patients with metastatic HER2 positive gastric cancer or gastro-esophageal junction (GEJ) cancer for anti-HER2 therapy approved by the U.S. Food and Drug Administration. The aim of this study was to identify the minimum biopsy set required to evaluate the HER2 status with confidence. PATIENTS AND METHODS: A total of 103 consecutive patients with resected gastric cancer or GEJ cancer were retrospectively selected; 2 formalin fixed, paraffin-embedded samples of each surgical specimen and all paired endoscopic biopsies were analyzed for HER2 status with both immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) methods. A total of 10 virtual biopsies were constructed by selecting areas 2.6 mm in diameter on the luminal side of digitalized slides obtained from the surgical specimens. The results of evaluating HER2 status in virtual biopsies, slides containing complete surgical specimens, and endoscopic biopsies were compared. The resulting minimum biopsy set was applied to the endoscopic biopsy series for validation. RESULTS: A biopsy set containing a minimum of 5 samples was identified as the most accurate in predicting HER2 status (sensitivity, 92 %; specificity, 97 %). In only 3 of the 103 cases (2.9 %) did a comparison of the HER2 evaluation of virtual biopsies and that of entire slides show inconsistent results. Overall agreement between the endoscopic biopsies and surgical samples for HER2 IHC status increased from 78.4 % to 92.3 % when biopsy sets containing 4 or fewer samples were compared with biopsy sets containing 5 or more samples. CONCLUSIONS: Although the recommendations suggest that 8 to 10 biopsies are necessary, the results show that a minimum set of 5 biopsies may be sufficient for reliable HER2 assessment in gastric cancer and GEJ cancer. However, endoscopists should be aware that a smaller sample size may be less accurate in selecting patients eligible for anti HER2 therapy. PMID- 26135664 TI - ENDOGENOUS CARBON MONOXIDE CONCENTRATION IN BLOOD ELEVATES IN ACUTE CORONARY SYNDROME OF NONSMOKER POPULATION. AB - BACKGROUND: Carbon monoxide (CO) was previously only considered as a highly toxic pollutant since it binds to hemoglobin with high affinity. Recently, however, it has been recognized as a signaling molecule with regulatory roles in many physiological and pathophysiological processes within the cardiovascular system. The aim of this study was to clarify the behavior of CO in patients with acute coronary syndrome (ACS). METHODS: We assessed 235 patients with suspected ACS, 98 smokers (88 male, 62 +/- 14 years) and 137 nonsmokers (77 male, 72 +/- 13 years), who had undergone emergent cardiac catheterization and blood sampling for calculation of carboxyhemoglobin (COHb). Patients were categorized into 4 groups: smoking patients with ACS (n=77), smoking patients without ACS (n=21), non smoking patients with ACS (n=97), and non-smoker patients without ACS (n=40). We investigated whether biomarkers were related to COHb levels. RESULTS: LogCOHb was significantly higher in the smoking patients compared to non-smoking patients (0.30 +/- 0.12 vs. 0.45 +/- 0.18, P < 0.01). Interestingly, among the non-smoking patients, COHb was increased in the ACS patients compared to the non ACS patients (0.31 +/- 0.12 vs. 0.25 +/- 0.12 P < 0.01). In contrast, among the smoking patients, there was no difference in COHb between the ACS and non-ACS patients (0.45 +/- 0.18 vs. 0.44 +/- 0.18, n.s.). There were no correlations between COHb and any of the biomarkers. CONCLUSIONS: These results suggest that endogenous CO may be useful to assess the risk of cardiovascular stress. PMID- 26135665 TI - STENTING STRATEGY AND FOLLOW-UP RESULTS OF MULTI-CENTER REGISTRY IN FUKUSHIMA CITY FOR LEFT MAIN CORONARY ARTERY DISEASE: BARE METAL STENT VERSUS DRUG-ELUTING STENT. AB - An appropriate treatment strategy for left main trunk (LMT) lesions is still controversial in the drug-eluting stent (DES) era. Consecutive LMT stenting cases (n = 155) between January 2008 and January 2013 in 4 hospitals in Fukushima city were retrospectively analyzed. We excluded the patients suffering from cardiogenic shock before the stenting procedure. Among those cases, 60 patients had acute coronary syndrome, and remaining 95 had stable angina pectoris. Out of 155 cases, 45 patients were treated with bare metal stents (BMSs) and 110 patients were treated with DESs. All cases were succeeded in the initial procedure. Mean stent size of BMS was 3.85 +/- 0.34 mm while that of DES was 3.46 +/- 0.17 mm (P<0.001). At the follow up coronary angiography (255-day on average), % stenosis of BMS group was 26.6 +/- 15.0% and that of DES group was 20.4 +/- 12.6% (P = 0.006). The mean observation period for clinical events was 738.8 +/- 480.3 days. Major adverse cardiac events-free rates for each group were compared and no significant differences were evident between the 2 groups (11.1% vs. 19.1%, ns). The present study demonstrated that use of BMSs would be a viable option in the treatment of LMT lesions when it is possible to use a large-sized stent (>3.5 mm). PMID- 26135667 TI - Inflammation-induced S100A8 activates Id3 and promotes colorectal tumorigenesis. AB - The aberrant expression of S100A8 and S100A9 is linked to nonresolving inflammation and ultimately to carcinogenesis, whereas the underlying mechanism that allows inflammation to progress to specific cancer types remains unknown. Here, we report that S100A8 was induced by inflammation and then promoted colorectal tumorigenesis downstream by activating Id3 (inhibitor of differentiation 3). Using gene expression profiling and immunohistochemistry, we found that both S100A8 and S100A9 were upregulated in the chemically-induced colitis-associated cancer mouse model and in human colorectal cancer specimens. Furthermore, we showed that S100A8 and S100A9 acted as chemoattractant proteins by recruiting macrophages, promoting the proliferation and invasion of colon cancer cell, as well as spurring the cycle that culminates in the acceleration of cancer metastasis in a nude mouse model. S100A8 regulated colon cancer cell cycle and proliferation by inducing Id3 expression while inhibiting p21. Id3 expression was regulated by Smad5, which was directly phosphorylated by Akt1. Our study revealed a novel mechanism in which inflammation-induced S100A8 promoted colorectal tumorigenesis by acting upstream to activate the Akt1-Smad5-Id3 axis. PMID- 26135666 TI - ANTI-TUMOR IMMUNE RESPONSES INDUCED BY RADIOTHERAPY: A REVIEW. AB - An anti-tumor immune response is one of the most important factors that can determine treatment response and prognosis of cancer patients. Recent studies have demonstrated that radiotherapy can activate tumor-specific immune responses and that these responses contribute to the therapeutic efficacy. However, the exact mechanisms underlying the radiation-induced immune responses remain unclear. Better understanding of the mechanisms could facilitate the application of immune-activating radiotherapy and provide new treatment strategies. We previously demonstrated that tumor-specific T cell responses could be induced in esophageal cancer patients during and after chemoradiotherapy. Furthermore, in a mouse model, immune responses played an important role in determining the local and systemic therapeutic efficacy of radiotherapy that could be augmented by the immune checkpoint blockade. In this review, radiotherapy-induced immune responses, the mechanisms underlying the induction of those responses, and a practical application of the therapy are discussed. PMID- 26135668 TI - Streptococcus gallolyticus: a single bacteria, two different conditions. AB - The authors describe the case of a 48-year-old woman presenting with fever, joint pain and migratory skin lesions. She had no other symptoms or medical history. After an extensive and inconclusive work up, she was admitted to the hospital for further study. This patient was ultimately found to have Streptococcus gallolyticus subsp gallolyticus bacteraemia. This finding led to the diagnosis of mitral valve infective endocarditis related to an underlying rectum adenocarcinoma. This article points out diagnostic difficulties related to an unusual presentation of the underlying disease. Furthermore, the authors reinforce the need of keeping a high level of suspicion and a systematic approach in every case of fever of unknown origin. This case highlights the importance of performing a colonoscopy in the event of S. gallolyticus subsp gallolyticus bacteraemia, as it may provide an opportunity for detecting colonic lesions at an earlier stage. PMID- 26135669 TI - Use of expiratory CT images in the diagnosis and localisation of airway complications following lung transplantation. PMID- 26135671 TI - A Review on Chemical Profile of Coumarins and their Therapeutic Role in the Treatment of Cancer. AB - Coumarin class of organic compounds consists of 1,2-benzopyrone ring system as a basic parent scaffold. These benzopyrones are subdivided into alpha-benzopyrones and gammabenzopyrones; with coumarin class of compounds belonging to alpha benzopyrones. Since the last few years, coumarins were synthesized in many of their derivative forms. Their pharmacological, therapeutic and biochemical properties depend upon their pattern of substitution. Coumarins exhibit a wide range of pharmacological activities, which includes anti-diabetic, anti-viral, anti-microbial, anticancer, anti-oxidant, anti-parasitic, anti-helminthic, anti proliferative, anti-convulsant, anti-inflammatory and antihypertensive activities. Among these properties, the present review article compiles the detailed research findings of coumarins as anti-cancer agents. Research reports reveal that coumarins inhibit human malignant tumor cell lines in vitro and also show anti-proliferative activity against many mammalian tumors in vivo. Clinical trials conducted on these coumarin class of compounds showed promising activity against several types of cancer such as breast cancer, lung cancer, malignant melanoma, prostate cancer and metastatic renal cell carcinoma etc. This review presents a comprehensive and up to date literature survey on coumarins as anti cancer agents. Furthermore, a detailed overview of various clinical trials conducted on coumarin class of compounds tested for various types of malignancies has been described. PMID- 26135672 TI - Therapeutic challenges after successful thrombectomy in a patient with an antiphospholipid syndrome associated M1-occlusion: A case report. AB - BACKROUND: Stroke is a frequent disorder in patients with an antiphospholipid syndrome (APS). Due to a high risk for further thromboembolic events, appropriate anticoagulation therapy in patients with an APS-associated stroke seems mandatory but drug eluting and duration is a matter of debate. CASE: A 48-year-old female patient presented with Broca's aphasia and mild hemiparesis on the right side. Diagnostic work-up revealed left middle cerebral artery (MCA) occlusion yet without diffusion-weighted lesions. Due to a thrombocytopenia (67.00 g/l) systemic thrombolysis was not indicated and endovascular treatment was initiated 150 min after symptom onset. After successful clot retrieval, recurrent re occlusions lead to the necessity of stent implantation and anticoagulation, respectively. On day 5 she developed a new severe right-sided hemiparesis. The magnetic resonance imaging (MRI) showed a subtotal restenosis of the left MCA despite the regular anticoagulation regime leading to a new left MCA ischaemic stroke. In the meantime, the unknown aetiology, the patients' age and the thrombocytopenia let to further diagnostic workup. Elevated blood parameters such as lupus anticoagulant (LA)-1, LA-ratio, positive anti-nuclear antibody (ANA), p anti-neutrophil cytoplasmic antibodies (ANCA), c-ANCA confirmed the diagnosis of APS. CONCLUSION: This case report showed the feasibility of mechanical clot retrieval and stent implantation in patients with APS. Due to the elevated risk of in-stent thrombosis a prolonged therapy with glycoprotein (GP)IIb/IIIa receptor antagonists in the initial postoperative period and further anticoagulation with coumarin derivate might be needed. PMID- 26135673 TI - Photocatalytic CO2 Reduction to Formate Using a Mn(I) Molecular Catalyst in a Robust Metal-Organic Framework. AB - A manganese bipyridine complex, Mn(bpydc)(CO)3Br (bpydc = 5,5'-dicarboxylate-2,2' bipyridine), has been incorporated into a highly robust Zr(IV)-based metal organic framework (MOF) for use as a CO2 reduction photocatalyst. In conjunction with [Ru(dmb)3](2+) (dmb = 4,4'-dimethyl-2,2'-bipyridine) as a photosensitizer and 1-benzyl-1,4-dihydronicotinamide (BNAH) as a sacrificial reductant, Mn incorporated MOFs efficiently catalyze CO2 reduction to formate in DMF/triethanolamine under visible-light irradiation. The photochemical performance of the Mn-incorporated MOF reached a turnover number of approximately 110 in 18 h, exceeding that of the homogeneous reference systems. The increased activity of the MOF-incorporated Mn catalyst is ascribed to the struts of the framework providing isolated active sites, which stabilize the catalyst and inhibit dimerization of the singly reduced Mn complex. The MOF catalyst largely retained its crystallinity throughout prolonged catalysis and was successfully reused over several catalytic runs. PMID- 26135674 TI - Cannabinoid and nitric oxide signaling interplay in the modulation of hippocampal hyperexcitability: Study on electrophysiological and behavioral models of temporal lobe epilepsy in the rat. AB - A growing bulk of evidence suggests that cannabinoid system plays a pivotal role in the control of hyperexcitability phenomena. Notwithstanding, the anticonvulsant action of cannabinoids has not been fully addressed, in particular the involvement of potential cellular neuromodulators, for instance nitric oxide. In the current study, we focused on two distinct rat models of temporal lobe epilepsy, the Maximal Dentate Activation and the pilocarpine-induced acute seizures, providing both electrophysiological and behavioral data on cannabinoid and nitrergic system interplay. We evaluated the antiepileptic effects of WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de] 1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), a CB agonist, and of 7 Nitroindazole (7NI), a preferential neuronal nitric oxide synthase (nNOS) inhibitor, at different doses, alone and in combination. MDA study showed that these drugs protected animals in a dose-dependent manner from electrically induced epileptiform discharges. In pilocarpine model, a dose-related activity of 7NI and WIN: a) decreased the behavioral scoring, used to describe the severity of chemically induced acute seizures; b) affected latency of the onset of acute convulsions; c) dampened mortality rate. Interestingly, the combination of the treatments brought to light that individually ineffective doses of WIN turn into effective when nNOS activity is pharmacologically inhibited in both experimental conditions. This effect is mediated by CB1 receptor since the co-administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H pyrazole-3-carboxamide (AM251), a CB1 receptor specific antagonist, thwarted the 7NI-WIN convergent action. In the light of this, our findings suggest a putative antagonism between CBr-activated pathway and NO signaling in the context of neuronal hyperexcitability and contribute to elucidate possible synaptic processes underlying neuroprotective properties of cannabinoids, with a view to better integrate antiepileptic therapy. PMID- 26135675 TI - Harpagoside ameliorates the amyloid-beta-induced cognitive impairment in rats via up-regulating BDNF expression and MAPK/PI3K pathways. AB - So far, no effective disease-modifying therapies for Alzheimer's disease (AD) aiming at protecting or reversing neurodegeneration of the disease have been established yet. The present work aims to elucidate the effect of Harpagoside (abbreviated HAR), an iridoid glycosides purified from the Chinese medicinal herb Scrophularia ningpoensis, on neurodegeneration induced by beta-amyloid peptide (Abeta) and the underlying molecular mechanism. Here we show that HAR exerts neuroprotective effects against Abeta neurotoxicity. Rats injected aggregated Abeta1-40 into the bilateral hippocampus displayed impaired spatial learning and memory ability in a Y-maze test and novel object recognition test, while HAR treatment ameliorated Abeta1-40-induced behavioral deficits. Moreover, administration of HAR increased the expression levels of brain-derived neurotrophic factor (BDNF) and activated the extracellular-regulated protein kinase (ERK) and the phosphatidylinositol 3-kinase (PI3-kinase) pathways both in the cerebral cortex and hippocampus of the Abeta1-40-insulted rat model. Furthermore, in cultured primary cortical neurons, Abeta1-42 induced significant decrease of choline acetyltransferase (ChAT)-positive neuron number and neurite outgrowth length, both of which were dose dependently increased by HAR. In addition, HAR pretreatment also significantly attenuated the decrease of cell viability in Abeta1-42-injured primary cortical neurons. Finally, when K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody were added to the culture medium 2 h prior to HAR addition, the protective effect of HAR on Abeta1-42-induced neurodegeneration in the primary cortical neuron was almost inhibited. Taken together, HAR exerting neuroprotection effect and ameliorating learning and memory deficit appears to be associated, at least in part, with up regulation of BDNF content as well as activating its downstream signaling pathways, e.g., MAPK/PI3K pathways. It raises the possibility that HAR has potential to be a therapeutic agent against AD. PMID- 26135676 TI - Viral nematics in confined geometries. AB - Motivated by recent experiments on the rod-like virus bacteriophage fd, confined to circular and annular domains, we present a theoretical study of structural transitions in these geometries. Using the continuum theory of nematic liquid crystals, we examine the competition between bulk elasticity and surface anchoring, mediated by the formation of topological defects. We show analytically that bulk defects are unstable with respect to defects sitting at the boundary. In the case of an annulus, whose topology does not require the presence of topological defects, we find that nematic textures with boundary defects are stable compared to defect-free configurations when the anchoring is weak. Our simple approach, with no fitting parameters, suggests a possible symmetry breaking mechanism responsible for the formation of one-, two- and three-fold textures under annular confinement. PMID- 26135677 TI - Identification of novel targets for the diagnosis and treatment of liver fibrosis. AB - Liver fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) in the hepatic parenchyma and represents an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. Hepatic stellate cells (HSCs) are the major cell type responsible for liver fibrosis. Following liver injury, HSCs become activated and transdifferentiate into myofibroblasts (MFBs) that lead to intrahepatic ECM accumulation. In the present study, we performed a meta-analysis of datasets which included whole-genome transcriptional data on HSCs in the quiescent and activated state from two different rodent species and identified commonly regulated genes. Several of the genes identified, including ECM components, metalloproteinases and growth factors, were found to be well-known markers for HSC activation. However, other significant genes also appeared to play important roles in hepatic fibrosis. The elucidation of the molecular events underlying HSC activation may be key to the identification of potential novel pharmacological targets for the prevention and treatment of liver fibrosis. PMID- 26135678 TI - Epidemiology and Prevention of Postsurgical Adhesions Revisited. AB - OBJECTIVE: To provide a comprehensive review of recent epidemiologic data on the burden of adhesion-related complications and adhesion prevention. Second, we elaborate on economic considerations for the application of antiadhesion barriers. BACKGROUND: Because the landmark SCAR studies elucidated the impact of adhesions on readmissions for long-term complications of abdominal surgery, adhesions are widely recognized as one of the most common causes for complications after abdominal surgery. Concurrently, interest in adhesion prevention revived and several new antiadhesion barriers were developed. Although these barriers have now been around for more than a decade, adhesion prevention is still seldom applied. METHODS: The first part of this article is a narrative review evaluating the results of recent epidemiological studies on adhesion related complications and adhesion prevention. In part II, these epidemiological data are translated into a cost model of adhesion-related complications and the potential cost-effectiveness of antiadhesion barriers is explored. RESULTS: New epidemiologic data warrant a shift in our understanding of the socioeconomic burden of adhesion-related complications and the indications for adhesion prevention strategies. Increasing evidence from cohort studies and systematic reviews shows that difficulties during reoperations, rather than small bowel obstructions, account for the majority of adhesion-related morbidity. Laparoscopy and antiadhesion barriers have proven to reduce adhesion formation and related morbidity. The direct health care costs associated with treatment of adhesion related complications within the first 5 years after surgery are $2350 following open surgery and $970 after laparoscopy. Costs are about 50% higher in fertile age female patients. Application of an antiadhesion barriers could save between $328 and $680 after open surgery. After laparoscopy, the costs impact ranges from $82 in expenses to $63 of savings. CONCLUSIONS: Adhesions are an important cause for long-term complications in both open and laparoscopic surgery. Adhesiolysis during reoperations seems to impact adhesion-related morbidity most. Routine application of antiadhesion barriers in open surgery is safe and cost-effective. Application of antiadhesion barriers can be cost-effective in selected cases of laparoscopy. More research is needed to develop barriers suitable for laparoscopic use. PMID- 26135682 TI - Quality of Life and Surgical Outcome 1 Year After Open and Laparoscopic Incisional Hernia Repair: PROLOVE: A Randomized Controlled Trial. AB - OBJECTIVE: Patients suffering from an incisional hernia after abdominal surgery have an impaired quality of life (QoL). Surgery aims to improve QoL with a minimum risk of further complications. The aim was to analyze QoL, predictors for outcome, including recurrence and reoperation rates during the first postoperative year. METHODS: In a randomized controlled trial comparing laparoscopic and open mesh repair, 133 patients were assessed preoperatively and after 1 year with regard to QoL using the Short Form-36 (SF-36), visual analog scale (pain, movement limitation, and fatigue), and questions addressing abdominal wall complaints. Factors concerning recurrence, reoperations, satisfaction, and improved QoL were analyzed. RESULTS: A total of 124 patients remained for analysis. All SF-36 scores except mental composite score increased, reaching and maintaining levels of the Swedish norm already after 8 weeks with no difference between groups. Event-free recovery was seen in 85% in the laparoscopic group and in 65% of the open cases (P < 0.010). Five recurrences occurred after laparoscopic surgery and 1 in the open group (P < 0.112). Overall, abdominal wall complaints decreased from 82% to 13% of the patients; and 92% were satisfied with the result after 1 year.In univariable logistic regression analyses laparoscopic surgery and male sex predicted an event-free recovery. Obesity (BMI > 30) predicted better outcome with regard to QoL. No predictors for recurrence or satisfaction were identified. CONCLUSIONS: Patients with incisional hernia benefit substantially from surgery concerning QoL, independent of surgical technique. An event-free recovery occurred frequently after laparoscopic surgery. SF-36 seems well suited for assessing surgical outcome in patients after incisional hernia repair. PMID- 26135687 TI - Implications of Lymph Node Staging on Selection of Adjuvant Therapy for Gastric Cancer in the United States: A Propensity Score-matched Analysis. AB - OBJECTIVE: To compare the efficacy of adjuvant chemoradiotherapy (CRT) and chemotherapy alone (CA) in gastric adenocarcinoma patients undergoing gastrectomy in the United States (US). BACKGROUND: A majority of US gastric adenocarcinoma patients are inadequately staged (<15 nodes examined). Despite this, and limited data comparing adjuvant CRT with CA in US patients, national guidelines endorse CA in selected patients undergoing D2 lymphadenectomy. METHODS: Resected stage IB III gastric adenocarcinoma patients receiving adjuvant CRT or CA (n = 3008) were identified in the National Cancer Database (1998-2006). Cox regression identified covariates associated with overall survival (OS). CRT and CA cohorts were matched (3:1) by propensity scores based on the likelihood of receiving CA. OS was compared by Kaplan-Meier estimates. RESULTS: Adjuvant CA was associated with an increased risk of death (HR 1.29, P < 0.001) relative to CRT. Inadequate lymph node staging (LNS) and nodal positivity were strong predictors of risk-adjusted mortality (P < 0.001). After propensity score-matching, CRT demonstrated superior median OS compared with CA (36.1 vs 28.9 m; P < 0.0001), regardless of stage. CRT was superior to CA in inadequately staged patients (33.1 m vs 24.5 m; P < 0.001); this benefit was less pronounced with increasing nodal examination. CRT improved OS in node-positive disease (29.8 vs 22.2 m; P < 0.001), regardless of LNS adequacy. In node-negative disease, OS did not differ significantly between CRT and CA cohorts; however, node-negative patients undergoing inadequate LNS benefited from CRT. CONCLUSIONS: CRT is associated with improved stage-stratified OS compared with CA. Lymph node status and adequacy of surgical staging should influence adjuvant therapy selection in the United States. PMID- 26135688 TI - Is Graduate Medical Education a Public Good? PMID- 26135681 TI - Significance of Microscopically Incomplete Resection Margin After Esophagectomy for Esophageal Cancer. AB - OBJECTIVE: The objectives of this study were to establish if R1 resection margin after esophagectomy was (i) a poor prognostic factor independent of patient and tumor characteristics, (ii) a marker of tumor aggressiveness and (iii) to look at the impact of adjuvant treatment in this subpopulation. METHODS: Data were collected from 30 European centers from 2000 to 2010. Patients with an R1 resection margin (n = 242) were compared with those with an R0 margin (n = 2573) in terms of short- and long-term outcomes. Propensity score matching and multivariable analyses were used to compensate for differences in baseline characteristics. RESULTS: Independent factors significantly associated with an R1 resection margin included an upper third esophageal tumor location, preoperative malnutrition, and pathological stage III. There were significant differences between the groups in postoperative histology, with an increase in pathological stage III and TRG 4-5 in the R1 group. Total average lymph node harvests were similar between the groups; however, there was an increase in the number of positive lymph nodes seen in the R1 group. Propensity matched analysis confirmed that R1 resection margin was significantly associated with reduced overall survival and increased overall, locoregional, and mixed tumor recurrence. Similar observations were seen in the subgroup that received neoadjuvant chemoradiation. In R1 patients adjuvant therapy improved survival and reduced distant recurrence however failed to affect locoregional recurrence. CONCLUSIONS: This large multicenter European study provides evidence to support the notion that R1 resection margin is a prognostic indication of aggressive tumor biology with a poor long-term prognosis. PMID- 26135689 TI - Site and Stage of Colorectal Cancer Influence the Likelihood and Distribution of Disease Recurrence and Postrecurrence Survival: Data From the FACS Randomized Controlled Trial. AB - OBJECTIVES: To describe patterns of recurrence and postrecurrence survival in a large cohort of accurately staged patients with Dukes' A-C colorectal cancer. BACKGROUND: Recurrence remains a frequent cause of mortality after the treatment of colorectal cancer with curative intent. Understanding the likelihood and site of recurrence informs adjuvant treatment and follow-up. METHODS: Retrospective cohort analysis of data from the FACS (follow-up after colorectal cancer surgery) trial after a median 4.4 years of follow-up; postrecurrence survival was calculated using the Kaplan-Meier method. RESULTS: Complete data were available for 94% of patients; 189 (17%) patients had experienced recurrence. Incidence of recurrence varied according to the site of the primary (right colon: 51/379, 14%; left colon: 68/421, 16%; rectum: 70/332, 21%; P = 0.023) and initial stage (Dukes' A: 26/249, 10%; Dukes' B: 81/537, 15%; Dukes' C: 82/346, 24%; P < 0.0001). Pulmonary recurrence was most frequently associated with rectal tumors, and multisite/other recurrence with right-sided colonic tumors. Recurrences from lower-stage tumors were more likely to be treatable with curative intent (Dukes' A: 13/26, 50%; Dukes' B: 32/81, 40%; Dukes' C: 20/82, 24%; P = 0.03). Those with rectal tumors benefited most from follow-up (proportion with treatable recurrence: rectum 30/332, 9%; left colon 23/421, 6%; right colon 12/379, 3%; P = 0.003). Both initial stage (log rank P = 0.005) and site of primary (log rank P = 0.01) influenced postrecurrence survival. CONCLUSIONS: The likelihood and site of recurrence, and survival, are influenced by the site and stage of the primary tumor. Those with rectal cancers benefited most from follow-up.ISRCTN 41458548. PMID- 26135690 TI - Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial. AB - OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting. PMID- 26135691 TI - Diagnostic Accuracy of Inflammatory Markers As Early Predictors of Infection After Elective Colorectal Surgery: Results From the IMACORS Study. AB - BACKGROUND: Intra-abdominal infections are frequent and life-threatening complications after colorectal surgery. An early detection could diminish their clinical impact and permit safe early discharge. OBJECTIVE: This study aimed to find the most accurate marker for the detection of postoperative intra-abdominal infection and the appropriate moment to measure it. METHODS: A prospective, observational study was conducted in 3 centers. Consecutive patients undergoing elective colorectal surgery with anastomosis were included. C-reactive protein and procalcitonin were measured daily until the fourth postoperative day. Postoperative infections were recorded according to the definitions of the Centres for Diseases Control. The areas under the receiver operating characteristic curve were analyzed and compared to assess the diagnostic accuracy of each marker. RESULTS: Five-hundred and one patients were analyzed. The incidence of intra-abdominal infection was 11.8%, with 24.6% of patients presenting at least one infectious complication. Overall mortality was 1.2%. At the fourth postoperative day, C-reactive protein was more discriminating than procalcitonin for the detection of intra-abdominal infection (areas under the ROC curve: 0.775 vs 0.689, respectively, P = 0.03). Procalcitonin levels showed wide dispersion. For the detection of all infectious complications, C-reactive protein was also significantly more accurate than procalcitonin on the fourth postoperative day (areas under the ROC curve: 0.783 vs 0.671, P = 0.0002). CONCLUSIONS: C-reactive protein is more accurate than procalcitonin for the detection of infectious complications and should be systematically measured at the fourth postoperative day. It is a useful tool to ensure a safe early discharge after elective colorectal surgery. PMID- 26135695 TI - Postoperative Interleukin-6 Level and Early Detection of Complications After Elective Major Abdominal Surgery. AB - OBJECTIVE: To assess the association of systemic inflammation and outcome after major abdominal surgery. BACKGROUND: Major abdominal surgery carries a high postoperative morbidity and mortality rate. Studies suggest that inflammation is associated with unfavorable outcome. METHODS: Levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha and the systemic inflammatory response syndrome (SIRS) were assessed in 137 patients undergoing major abdominal surgery. Blood samples were drawn on days 0, 1, 3, and 7, and SIRS was scored during 48 hours after surgery. Primary outcome was a composite of mortality, pneumonia, sepsis, anastomotic dehiscence, wound infection, noncardiac respiratory failure, atrial fibrillation, congestive heart failure, myocardial infarction, and reoperation within 30 days of surgery. RESULTS: An IL-6 level more than 432 pg/mL on day 1 was associated with an increased risk of complications (adjusted odds ratio: 3.3; 95% confidence interval [CI]: 1.3-8.5) and a longer median length of hospital stay (7 vs 12 days, P < 0.001). As a single test, an IL-6 cut-off level of 432 pg/mL on day 1 yielded a specificity of 70% and a sensitivity of 64% for the prediction of complications (area under the curve: 0.67; 95% CI: 0.56-0.77). Levels of CRP started to discriminate from day 3 onward with a specificity of 87% and a sensitivity of 58% for a cut-off level of 203 mg/L (AUC: 0.73; 95% CI: 0.63-0.83). CONCLUSIONS: A high IL-6 level on day 1 is associated with postoperative complications. Levels of IL-6 help distinguish between patients at low and high risk for complications before changes in levels of CRP. PMID- 26135697 TI - Impact of Mesh Fixation on Chronic Pain in Total Extraperitoneal Inguinal Hernia Repair (TEP): A Nationwide Register-based Study. AB - BACKGROUND: Mesh fixation is used to prevent recurrence at the potential risk for chronic pain in TEP. The aim was to compare the impact of permanent fixation (PF) with no fixation (NF)/nonpermanent fixation (NPF) of mesh on chronic pain after TEP repair for primary inguinal hernia. METHODS: Men, 30 to 75 years old, consecutively registered in the Swedish Hernia Register for a TEP primary repair in 2005 to 2009, were included in a mail survey using SF-36 and the Inguinal Pain Questionnaire (IPQ). Primary endpoint was IPQ question "Did you have pain during past week that could not be ignored." Risk factors for chronic pain and recurrent operations were analyzed. RESULTS: A total of 1110 patients were included (325 PF, 785 NF/NPF) with 7.7% reporting pain at median 33 months follow-up. No difference regarding primary endpoint pain (P < 0.462), IPQ and SF-36 subscales were seen. Recurrent operation was carried out in 1.4% during 7.5 years follow-up with no difference between PF- and NF-groups including subgroups of medial hernias. All SF-36 subscale-scores were equal to or better than the Swedish norm. A postoperative complication was a risk factor for chronic pain (OR 2.44, 95% CI 1.23-5.25, P < 0.023). CONCLUSIONS: The TEP procedure for primary inguinal hernia repair in men is associated with a low frequency of chronic pain and recurrent operations, with no difference between permanent fixation and no/nonpermanent fixation of mesh in a nationwide population-based study. TEP without fixation reduces costs and is safe for all patients. PMID- 26135696 TI - Recurrence and Survival After Resection of Small Intraductal Papillary Mucinous Neoplasm-associated Carcinomas (<=20-mm Invasive Component): A Multi institutional Analysis. AB - BACKGROUND: Early invasive carcinoma may be encountered in association with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The natural history of these early invasive lesions is unknown. METHODS: Pancreatic surgical databases from 4 high-volume centers were queried for IPMNs, with invasive components measuring 20 mm or less. All cases were reviewed by GI gastrointestinal pathologists, and pathologic features were analyzed to identify predictors of recurrence and survival. RESULTS: A total of 70 small IPMN associated invasive carcinomas (<=20-mm invasion) were identified, comprising 25% of resected IPMN-associated carcinomas (n = 280). Most of these small invasive cancers were multifocal (66%), less than 10 mm in size (73%), and arose in the setting of a main duct IPMN (96%). The most common adenocarcinoma subtypes were tubular (57%) and colloid (29%). Lymph node metastases were present in 19% of cases and 23% were T3 lesions. The overall recurrence rate was 24% (n = 17), and the median time to recurrence was 16 months (range: 4-132 months). Median and 5 year survival rates were 99 months and 59%. Recurrence patterns of invasive disease were local in 35%, distant in 47%, and both in 18%. Lymphatic spread and T3 stage were predictive of recurrence (univariate, P = 0.006), whereas tubular carcinoma type was the most predictive of poor overall survival (multivariate hazard ratio = 3.7, P = 0.04). CONCLUSIONS: This study represents the largest multi-institutional experience of resected small IPMN-associated carcinoma. Although these malignancies may frequently be cured with resection, recurrence risk is significant. Lymphatic spread, increased T stage, and tubular type carcinoma were associated with the poorest outcome. PMID- 26135698 TI - Nomograms for Pre- and Postoperative Prediction of Long-term Survival for Patients Who Underwent Hepatectomy for Multiple Hepatocellular Carcinomas. AB - OBJECTIVES: To develop prognostic nomograms for patients undergoing hepatectomy for multiple hepatocellular carcinomas (mHCCs). BACKGROUND: The prognostic prediction after hepatectomy for mHCCs has not been well established. METHODS: A training cohort (n = 540) was analyzed to construct 2 nomograms based separately on data obtained before and after hepatectomy for mHCCs at the Eastern Hepatobiliary Surgery Hospital between 2000 and 2006. The internal and external validations were performed in 2 independent cohorts (n = 180 each) collected from the Eastern Hepatobiliary Surgery Hospital between 2007 and 2010 and the Sun Yat Sen University between 2000 and 2007. The predictive accuracy was measured by concordance index (C-index) and calibration curve. RESULTS: Serum alpha fetoprotein level, hepatitis B virus deoxyribonucleic acid load, end-stage liver disease score, tumor number, total tumor diameter, and the ratio of largest to smallest tumor diameter were incorporated into the preoperative nomogram for overall survival (OS) prediction. In addition to these variables, microvascular invasion, tumor capsule, type of hepatectomy, and local invasion/metastasis were incorporated into the postoperative nomogram. All calibration curves for probability of OS fitted well. In the training cohort, the preoperative nomogram achieved a C-index of 0.75 (95% confidence interval, 0.72-0.78) in predicting OS and accurately stratified patients into 4 prognostic subgroups (5-year OS rates: 65.9%, 46.3%, 29.6%, and 4.1%, P < 0.001). The postoperative nomogram had a C index of 0.80, which was higher than those of the 4 conventional staging systems (0.53-0.62). These results were supported by the internal and external validations. CONCLUSIONS: The 2 nomograms showed accurate pre- and postoperative prediction of posthepatectomy prognosis in patients with mHCCs. PMID- 26135699 TI - A New Paradigm of Injuries From Terrorist Explosions as a Function of Explosion Setting Type. AB - OBJECTIVE: Examine the impact of setting on the magnitude and pattern of civilian injuries from terrorist explosions. This may help surgical staffs anticipate the resources required to treat victims of terrorist attacks. METHODS: A retrospective study of 823 patients from 65 explosive events of the Second Intifada (2000-2005) in the National Trauma Registry. After verification all the events were divided into 5 categories: explosions inside buildings (CS), explosions near buildings (SO), explosions inside buses (IB), explosions near buses (AB), and explosions in an open space (OS). The categories were then compared in terms of sustained injuries, utilization of hospital resources and clinical outcomes. RESULTS: CS and IB scenarios were found to cause the most severe injuries, demanded the most hospital resources and had the worst outcomes, but had several important differences in injury profiles. AB setting proved to be a stand-alone scenario with the lowest severity, possibly due to protection provided to the passengers by the bus. The high volume of blast injuries in SO scenario supports the idea that the explosion wave could be reflected onto the people standing outside a building next to its wall. OS patients had the lowest proportion of blast trauma and burns. CONCLUSIONS: The existing taxonomy of terrorist bombings, which distinguishes explosions in open spaces from those occurring in closed environments, does not fully differentiate patterns of injury that follow blasts in intermediate environments. Expanding the framework from 2 categories to 5 appears to provide greater precision and may be clinically useful to health care providers. PMID- 26135700 TI - Measuring the Elastic Modulus of Thin Polymer Sheets by Elastocapillary Bending. AB - We describe bending by liquid/liquid or liquid/air interfaces as a simple and broadly applicable technique for measuring the elastic modulus of thin elastic sheets. The balance between bending and surface energies allows for the characterization of a wide range of materials with moduli ranging from kilopascals to gigapascals in both vapor and liquid environments, as demonstrated here by measurements of both soft hydrogel layers and stiff glassy polymer films. Compared to existing approaches, this method is especially useful for characterizing soft materials (=18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01752634. FINDINGS: Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6.81, 95% CI 3.42-13.56; p<0.0001), 150 mg (51 [51%] patients; 6.52, 3.25-13.08; p<0.0001), and 75 mg (29 [29%] patients; 2.32, 1.14-4.73; p=0.0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. INTERPRETATION: Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder. FUNDING: Novartis. PMID- 26135706 TI - Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double blind, non-inferiority trial. AB - BACKGROUND: High doses of intravenous methylprednisolone are recommended to treat relapses in patients with multiple sclerosis, but can be inconvenient and expensive. We aimed to assess whether oral administration of high-dose methylprednisolone was non-inferior to intravenous administration. METHODS: We did this multicentre, double-blind, randomised, controlled, non-inferiority trial at 13 centres for multiple sclerosis in France. We enrolled patients aged 18-55 years with relapsing-remitting multiple sclerosis who reported a relapse within the previous 15 days that caused an increase of at least one point in one or more scores on the Kurtzke Functional System Scale. With use of a computer-generated randomisation list and in blocks of four, we randomly assigned (1:1) patients to either oral or intravenous methylprednisolone, 1000 mg, once a day for 3 days. Patients, treating physicians and nurses, and data and outcome assessors were all masked to treatment allocation, which was achieved with the use of saline solution and placebo capsules. The primary endpoint was the proportion of patients who had improved by day 28 (decrease of at least one point in most affected score on Kurtzke Functional System Scale), without need for retreatment with corticosteroids, in the per-protocol population. The trial was powered to assess non-inferiority of oral compared with intravenous methylprednisolone with a predetermined non-inferiority margin of 15%. This trial is registered with ClinicalTrials.gov, number NCT00984984. FINDINGS: Between Jan 29, 2008, and June 14, 2013, we screened 200 patients and enrolled 199. We randomly assigned 100 patients to oral methylprednisolone and 99 patients to intravenous methylprednisolone with a mean time from relapse onset to treatment of 7.0 days (SD 3.6) and 7.4 days (3.9), respectively. In the per-protocol population, 66 (81%) of 82 patients in the oral group and 72 (80%) of 90 patients in the intravenous group achieved the primary endpoint (absolute treatment difference 0.5%, 90% CI -9.5 to 10.4). Rates of adverse events were similar, but insomnia was more frequently reported in the oral group (77 [77%]) than in the intravenous group (63 [64%]). INTERPRETATION: Oral administration of high-dose methylprednisolone for 3 days was not inferior to intravenous administration for improvement of disability scores 1 month after treatment and had a similar safety profile. This finding could have implications for access to treatment, patient comfort, and cost, but indication should always be properly considered by clinicians. FUNDING: French Health Ministry, Ligue Francaise contre la SEP, Teva. PMID- 26135707 TI - Redistribution through social health insurance: evidence on citizen preferences. AB - The extent of social health insurance (SHI) and supplementary private insurance is frequently analyzed in public choice. Most of these analyses build on the model developed by Gouveia (1997), who defines the extent of SHI as consequence of a choice by self-interested voters. In this model, an indicator reflecting individuals' relative income position and relative risk of falling ill determines the voting decision. Up to now, no empirical evidence for this key assumption has been available. We test the effect of this indicator on individuals' preferences for the extent of SHI in a setting with mandatory SHI that can be supplemented by private insurance. The data is based on a DCE conducted in the field with a representative sample of 1538 German citizens in 2012. Conditional logit and latent class models are used to analyze preference heterogeneity. Our findings strongly support the assumptions of the models. Individuals likely to benefit from public coverage show a positive marginal willingness to pay (MWTP) for both a shift away from other beneficiary groups toward the sick and an expansion of publicly financed resources, and the expected net payers have a negative MWTP and prefer lower levels of public coverage. PMID- 26135708 TI - Multi-shelled hollow micro-/nanostructures. AB - Great progress has been made in the preparation and application of multi-shelled hollow micro-/nanostructures during the past decade. However, the synthetic methodologies and potential applications of these novel and interesting materials have not been reviewed comprehensively in the literature. In the current review we first describe different synthetic methodologies for multi-shelled hollow micro-/nanostructures as well as their compositional and geometric manipulation and then review their applications in energy conversion and storage, sensors, photocatalysis, and drug delivery. The correlation between the geometric properties of multi-shelled hollow micro-/nanostructures and their specific performance in relevant applications are highlighted. These results demonstrate that the geometry has a direct impact on the properties and potential applications of such materials. Finally, the emerging challenges and future development of multi-shelled hollow micro-/nanostructures are further discussed. PMID- 26135709 TI - Scorpion envenomation cardiomyopathy: a promising model for takotsubo syndrome. PMID- 26135710 TI - Combined interventions are effective in MRSA control. AB - BACKGROUND: A large healthcare-associated epidemic mainly caused by one methicillin-resistant Staphylococcus aureus (MRSA) strain broke out in Pirkanmaa County, Finland, in 2001. This study describes the impact of infection control and screening practices on the epidemic. METHODS: The number of hospital-acquired (HA)-MRSA findings obtained from clinical and screening samples during the epidemic was calculated. Strains were typed by pulsed-field electrophoresis (PFGE) or spa typing. Strain type distribution was studied in relation to sample type, year of the epidemic and site of transmission. Several infection control interventions were launched stepwise and screening protocols were expanded. RESULTS: A total of 4118 cases were identified during 2001-2014, of which 3527 were classified as HA. One strain (spa t067) dominated in the epidemic. HA-MRSA cases decreased constantly from the year 2011. The number of new HA-MRSA cases was 57% less in the year 2014 (n = 171) as compared with the year 2011 (n = 399). The proportion of the epidemic strain declined significantly over the years. Screening samples comprised 71% (2439/3527) and clinical samples 29% (1034/3527) of HA-MRSA findings. The number of HA-MRSA cases found from clinical samples started to decrease when screening was expanded. An increase in hand-rub consumption was associated with a decrease in transmissions in Tampere University Hospital (TAUH). CONCLUSION: Implementation of universal screening together with several other interventions is effective in containing an MRSA epidemic. The proportion of other than Pirkanmaa epidemic (PE)-MRSA strain findings increased throughout the period, indicating the changing epidemiology of MRSA. PMID- 26135711 TI - Characterization of ESBL disseminating plasmids. AB - Bacteria producing extended-spectrum beta-lactamases (ESBLs) constitute a globally increasing problem that contributes to treatment complications and elevated death rates. The extremely successful dissemination by ESBL-producing Enterobacteriaceae during the latest decades is a result of the combination of mobilization, evolution and horizontal spread of beta-lactamase genes on plasmids. In parallel, spread of these plasmids to particularly well-adapted bacterial clones (outbreak clones) has expanded. In this review we describe ESBL producing bacteria and the genetic mechanisms for dissemination of ESBL resistance. We describe available methodology for studying plasmids and the importance of including plasmids in epidemiological typing as natural parts of the organisms. Plasmids play a fundamental role in how resistance arises and disseminates. PMID- 26135712 TI - Prevalence and specificity of RBC alloantibodies in the general hospitalised population in Guangxi. AB - OBJECTIVES: The aim of this work was to investigate the prevalence and specificities of red blood cell (RBC) alloantibodies in the general hospitalised population in Guangxi, China. BACKGROUND: Alloimmunisation to RBC antigens is a major complication of transfusion therapy, and alloantibodies pose many clinical problems such as blood transfusion-related adverse reactions. The frequency and specificity of erythrocyte alloantibodies were different in populations from different geographic areas and races. However, the data on alloantibodies in the Guangxi population are limited; thus, we aimed to investigate them in this study. METHODS: Erythrocyte request records of Guangxi patients were retrospectively reviewed from January 2013 to February 2014. Data from antibody screening tests for 20,283 patients were retrieved for analysis. Clinical data, including gender, age, medical history, transfusion history, pregnancy history and alloantibody specificity were collected. RESULTS: Data from 20,283 patients were analysed, and a total of 166 alloantibodies were identified in 150 patients (0.74%). The most frequent alloantibodies were anti-E (39.76%), anti-Mi(a)/Mur (11.45%), anti-c (10.84 %), anti-Le(a) (8.43%) and anti-M (6.63%). Three cases of anti-D (1.81%) and two rare cases of anti-H (1.20%) were also detected. CONCLUSIONS: The frequency and specificities of erythrocyte alloantibodies among hospitalised patients in Guangxi were different from those in other Chinese populations and Caucasians, although the alloantibodies against the antigens of the Rh system are still common. Anti-E and anti-Mi(a)/Mur were more common in Guangxi patients, but anti-K and anti-D, which are prone to develop in Caucasians, were less likely to develop in our patients. PMID- 26135713 TI - Single intra-articular dexamethasone injection immediately post-surgery in a rabbit model mitigates early inflammatory responses and post-traumatic osteoarthritis-like alterations. AB - Despite surgical reconstruction of the anterior cruciate ligament, a significant number of patients will still develop post-traumatic osteoarthritis (PTOA). Our objective was to determine if mitigating aspects of the acute phase of inflammation following a defined knee surgery with a single administration of a glucocorticoid could prevent the development of PTOA-like changes within an established rabbit model of surgically induced PTOA. An early and late post surgical time-point was investigated in this study (48 h and 9 weeks post surgery) in which the following groups were repeated (each n=6, for a total of 24 rabbits per time-point, and 48 rabbits used in the study): control (age/sex matched), sham (arthrotomy), drill injury (arthrotomy+two drill holes to a non cartilaginous area of the femoral notch), and drill injury+single intra-articular (IA) injection of dexamethasone (DEX). At 48 h post-surgery, DEX treatment significantly lowered the mRNA levels for a subset of pro-inflammatory mediators, and significantly lowered the histological grade. Nine weeks post surgery, DEX treatment significantly lowered the histological scores (presented as effect size) for synovium (3.8), lateral femoral condyle (3.9), and lateral tibial cartilage (5.1) samples. Thus, DEX likely acts to prevent injury induced inflammation that could contribute to subsequent joint damage. PMID- 26135714 TI - Discovery of GSK2795039, a Novel Small Molecule NADPH Oxidase 2 Inhibitor. AB - AIMS: The NADPH oxidase (NOX) family of enzymes catalyzes the formation of reactive oxygen species (ROS). NOX enzymes not only have a key role in a variety of physiological processes but also contribute to oxidative stress in certain disease states. To date, while numerous small molecule inhibitors have been reported (in particular for NOX2), none have demonstrated inhibitory activity in vivo. As such, there is a need for the identification of improved NOX inhibitors to enable further evaluation of the biological functions of NOX enzymes in vivo as well as the therapeutic potential of NOX inhibition. In this study, both the in vitro and in vivo pharmacological profiles of GSK2795039, a novel NOX2 inhibitor, were characterized in comparison with other published NOX inhibitors. RESULTS: GSK2795039 inhibited both the formation of ROS and the utilization of the enzyme substrates, NADPH and oxygen, in a variety of semirecombinant cell free and cell-based NOX2 assays. It inhibited NOX2 in an NADPH competitive manner and was selective over other NOX isoforms, xanthine oxidase, and endothelial nitric oxide synthase enzymes. Following systemic administration in mice, GSK2795039 abolished the production of ROS by activated NOX2 enzyme in a paw inflammation model. Furthermore, GSK2795039 showed activity in a murine model of acute pancreatitis, reducing the levels of serum amylase triggered by systemic injection of cerulein. INNOVATION AND CONCLUSIONS: GSK2795039 is a novel NOX2 inhibitor that is the first small molecule to demonstrate inhibition of the NOX2 enzyme in vivo. PMID- 26135715 TI - Hybrid nickel manganese oxide nanosheet-3D metallic dendrite percolation network electrodes for high-rate electrochemical energy storage. AB - This work reports the fabrication, by electrodeposition and post-thermal annealing, of hybrid electrodes for high rate electrochemical energy storage composed of nickel manganese oxide (Ni0.86Mn0.14O) nanosheets over 3D open porous dendritic NiCu foams. The hybrid electrodes are made of two different percolation networks of nanosheets and dendrites, and exhibit a specific capacitance value of 848 F g(-1) at 1 A g(-1). The electrochemical tests revealed that the electrodes display an excellent rate capability, characterized by capacitance retention of approximately 83% when the applied current density increases from 1 A g(-1) to 20 A g(-1). The electrodes also evidenced high charge-discharge cycling stability, which attained 103% after 1000 cycles. PMID- 26135717 TI - Hypervolume Subset Selection in Two Dimensions: Formulations and Algorithms. AB - The hypervolume subset selection problem consists of finding a subset, with a given cardinality k, of a set of nondominated points that maximizes the hypervolume indicator. This problem arises in selection procedures of evolutionary algorithms for multiobjective optimization, for which practically efficient algorithms are required. In this article, two new formulations are provided for the two-dimensional variant of this problem. The first is a (linear) integer programming formulation that can be solved by solving its linear programming relaxation. The second formulation is a k-link shortest path formulation on a special digraph with the Monge property that can be solved by dynamic programming in [Formula: see text] time. This improves upon the result of [Formula: see text] in Bader ( 2009 ), and slightly improves upon the result of [Formula: see text] in Bringmann et al. ( 2014b ), which was developed independently from this work using different techniques. Numerical results are shown for several values of n and k. PMID- 26135718 TI - Unbiased Black-Box Complexities of Jump Functions. AB - We analyze the unbiased black-box complexities of jump functions with small, medium, and large sizes of the fitness plateau surrounding the optimal solution. Among other results, we show that when the jump size is (1/2 - epsilon), that is, when only a small constant fraction of the fitness values is visible, then the unbiased black-box complexities for arities 3 and higher are of the same order as those for the simple OneMax function. Even for the extreme jump function, in which all but the two fitness values n/2 and n are blanked out, polynomial time mutation-based (i.e., unary unbiased) black-box optimization algorithms exist. This is quite surprising given that for the extreme jump function almost the whole search space (all but a Theta(n(-1/2)) fraction) is a plateau of constant fitness. To prove these results, we introduce new tools for the analysis of unbiased black-box complexities, for example, selecting the new parent individual not only by comparing the fitnesses of the competing search points but also by taking into account the (empirical) expected fitnesses of their offspring. PMID- 26135719 TI - Maximizing Submodular Functions under Matroid Constraints by Evolutionary Algorithms. AB - Many combinatorial optimization problems have underlying goal functions that are submodular. The classical goal is to find a good solution for a given submodular function f under a given set of constraints. In this paper, we investigate the runtime of a simple single objective evolutionary algorithm called (1 + 1) EA and a multiobjective evolutionary algorithm called GSEMO until they have obtained a good approximation for submodular functions. For the case of monotone submodular functions and uniform cardinality constraints, we show that the GSEMO achieves a (1 - 1/e)-approximation in expected polynomial time. For the case of monotone functions where the constraints are given by the intersection of K >= 2 matroids, we show that the (1 + 1) EA achieves a (1/k + delta)-approximation in expected polynomial time for any constant delta > 0. Turning to nonmonotone symmetric submodular functions with k >= 1 matroid intersection constraints, we show that the GSEMO achieves a 1/((k + 2)(1 + epsilon))-approximation in expected time O(n(k + 6)log(n)/epsilon. PMID- 26135720 TI - [Whether steam or smoke: smoking cessation is still the most effective prevention]. PMID- 26135721 TI - [CME. Fabry disease: rare but not to be missed]. PMID- 26135723 TI - [Electronic Cigarettes: Lifestyle Gadget or Smoking Cessation Aid?]. AB - Electronic cigarettes (e-cigarettes) are vaporisers of liquids often containing nicotine. In the inhaled aerosol carcinogens, ultrafine and metal particles are detected usually in concentrations below those measured in tobacco smoke. Therefore, these products are expected to be less harmful. This has not yet been proven. The long-term safety of e-cigarettes is unknown. Short duration use leads to airway irritation and increased diastolic blood pressure. So far only two randomised controlled trials have investigated efficacy and safety of e cigarettes for smoking cessation: No clear advantage was shown in comparison to smoking cessation medication. Due to insufficient evidence, e-cigarettes cannot be recommended for smoking cessation. Problematic are the lack of regulation and standardisation of e-cigarette products, which makes general conclusions impossible. PMID- 26135724 TI - [E-Cigarettes - Friend or Foe?]. AB - Not nicotine, but an abundant amount of toxic chemicals produced by the combustion of tobacco are the cause of well-known health problems. E-cigarette vapor contains no or only minimal quantities of potentially harmful substances. Hence it can be assumed that vaping in adults is much less harmful than smoking of cigarettes. Furthermore, no data exist that e-cigarettes will encourage youngsters to become cigarette smokers. E-cigarette vaping has the potential to reduce the daily number of cigarettes smoked or facilitates cessation of smoking in heavily nicotine-dependent smokers, who keep on smoking despite a structured smoking cessation program. Health professionals should be aware of this type of nicotine substitution, since the controversial discussion is often emotional and not evidence-based. PMID- 26135725 TI - [Advanced and Metastatic Lung Cancer - What is new in the Diagnosis and Therapy?]. AB - Lung cancer is one of the most common types of malignancies worldwide. The majority of patients are diagnosed with an incurable advanced/metastatic stage disease. Palliative treatment approaches improve the survival and the quality of life of these patients. Lung cancer is subdivided according to histology and molecular biology. The most important classification separates small cell from non-small cell lung cancer. In the subgroup of non-small cell lung cancer novel treatment approaches coming along with an improved prognosis have been established during the last decade. The current manuscript provides an overview on current treatment options for metastatic lung cancer. Furthermore, an outlook on promising future treatment options is provided. PMID- 26135726 TI - [Pancytopenia, Hemolytic Anemia and Schizocytes: a Pragmatic Approach]. AB - A 58 year old woman presents with a progressive fatigue and dyspnea associated with paresthesia. Laboratory tests show pancytopenia with hypersegmented neutrophiles, macrocytic hyporegenerative anemia and arguments for hemolysis, in particular highly increased LDH. This constellation strongly suggests vitamin B12 deficiency, which was confirmed with an undetectable cobalamine concentration in the blood of our patient. The etiologic work up shows the presence of anti parietal cells antibodies at a titer of 1/640, diagnostic of Biermer anemia. PMID- 26135727 TI - [Diabetes prevention: Metformin works well, lifestyle modification is more effective]. PMID- 26135728 TI - [Paracetamol is ineffective for back pain and only minimally effective for osteoarthritis]. PMID- 26135730 TI - [CME Dermatology. Pruritus and white lesions of the trunk. Lichen sclerosus]. PMID- 26135732 TI - Emergence of porcine epidemic diarrhea virus in southern Germany. AB - BACKGROUND: Over the last years, porcine epidemic diarrhea virus (PEDV) has caused devastating enteric diseases in the US and several countries in Asia, while outbreaks in Europe have only been reported sporadically since the 1980s. At present, only insufficient information is available on currently circulating PEDV strains in Europe and their impact on the European swine industry. In this case report, we present epidemic outbreaks of porcine epidemic diarrhea in three farms in South-Western Germany. CASE PRESENTATION: Epidemic outbreaks of diarrhea affecting pigs of all age groups were reported in three farms, one fattening farm and two piglet producing farms, in South-Western Germany between May and November 2014. In the fattening farm yellowish, watery diarrhea without evidence of mucus or blood was associated with a massive reduction of feed consumption. Severity of clinical signs and mortality in young suckling pigs varied significantly between the two affected sow farms. While mortality in suckling piglets reached almost 70 % in one sow herd, no increase in suckling piglet mortality was observed in the second sow farm. In all three cases, PEDV was confirmed in feces and small intestines by RT-qPCR. Phylogenetic analyses based on full-length PEDV genomes revealed high identity among strains from all three herds. Moreover, the German strains showed very high nucleotide identity (99.4 %) with a variant of PEDV (OH851) that was isolated in the United States in January 2014. This strain with insertions and deletions in the S-gene (so called INDEL strains) was reported to show lower virulence. Slightly lower identities were found with other strains from the US and Asia. CONCLUSION: Phylogenetic information on the distribution of PEDV strains in Europe is severely lacking. In this case report we demonstrate that acute outbreaks of PEDV occurred in southern Germany in 2014. Current strains were clearly different from isolates found in the 1980s and were closely related to a PEDV variant found in the US in 2014. Moreover, the present case report indicates that variant strains of PEDV, containing insertions and deletions in the S gene, which were reported to be of lower virulence, might be able to cause high mortality in suckling piglets. PMID- 26135733 TI - No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients. AB - AIM: Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. METHODS: All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 - September 2013), and for whom >=6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. RESULTS: Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had >=6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman - with advanced pre-radiograph stage (IVA) disease - showed findings consistent with pulmonary metastases. Radiographs of 7 other women - 4 early, 3 advanced stage disease - were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. CONCLUSION: Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years. PMID- 26135734 TI - Melioidosis Cases and Selected Reports of Occupational Exposures to Burkholderia pseudomallei--United States, 2008-2013. AB - PROBLEM/CONDITION: Melioidosis is an infection caused by the Gram-negative bacillus Burkholderia pseudomallei, which is naturally found in water and soil in areas endemic for melioidosis. Infection can be severe and sometimes fatal. The federal select agent program designates B. pseudomallei as a Tier 1 overlap select agent, which can affect both humans and animals. Identification of B. pseudomallei and all occupational exposures must be reported to the Federal Select Agent Program immediately (i.e., within 24 hours), whereas states are not required to notify CDC's Bacterial Special Pathogens Branch (BSPB) of human infections. PERIOD COVERED: 2008-2013. DESCRIPTION OF SYSTEM: The passive surveillance system includes reports of suspected (human and animal) melioidosis cases and reports of incidents of possible occupational exposures. Reporting of suspected cases to BSPB is voluntary. BSPB receives reports of occupational exposure in the context of a request for technical consultation (so that the system does not include the full complement of the mandatory and confidential reporting to the Federal Select Agent Program). Reporting sources include state health departments, medical facilities, microbiologic laboratories, or research facilities. Melioidosis cases are classified using the standard case definition adopted by the Council of State and Territorial Epidemiologists in 2011. In follow up to reports of occupational exposures, CDC often provides technical assistance to state health departments to identify all persons with possible exposures, define level of risk, and provide recommendations for postexposure prophylaxis and health monitoring of exposed persons. RESULTS: During 2008-2013, BSPB provided technical assistance to 20 U.S. states and Puerto Rico involving 37 confirmed cases of melioidosis (34 human cases and three animal cases). Among those with documented travel history, the majority of reported cases (64%) occurred among persons with a documented travel history to areas endemic for melioidosis. Two persons did not report any travel outside of the United States. Separately, six incidents of possible occupational exposure involving research activities also were reported to BSPB, for which two incidents involved occupational exposures and no human infections occurred. Technical assistance was not required for these incidents because of risk-level (low or none) and appropriate onsite occupational safety response. Of the 261 persons at risk for occupational exposure to B. pseudomallei while performing laboratory diagnostics, 43 (16%) persons had high-risk exposures, 130 (50%) persons had low-risk exposures, and 88 (34%) persons were classified as having undetermined or unknown risk. INTERPRETATION: A small number of U.S. cases of melioidosis have been reported among persons with no travel history outside of the United States, whereas the majority of cases have occurred in persons with a travel history to areas endemic for melioidosis. If the number of travelers continues to increase in countries where the disease is endemic, the likelihood of identifying imported melioidosis cases in the United States might also increase. PUBLIC HEALTH ACTIONS: Reporting of melioidosis cases can improve the ability to monitor the incidence and prevalence of the disease in the United States. To improve prevention and control of melioidosis, CDC recommends that (1) physicians consider melioidosis in the differential diagnosis of patients with acute febrile illnesses, risk factors for melioidosis, and compatible travel or exposure history; (2) personnel at risk for occupational exposure (e.g., laboratory workers or researchers) follow proper safety practices, which includes using appropriate personal protective equipment when working with unknown pathogens; and (3) all possible occupational exposures to B. pseudomallei be reported voluntarily to BSPB. PMID- 26135735 TI - Ambient-Temperature Ortho C-H Arylation of Benzoic Acids with Aryl Iodides with Ligand-Supported Palladium Catalyst. AB - The ambient-temperature ortho C-H arylation of electron-deficient benzoic acids with aryl iodides has been achieved by using an Ac-Ile-OH-supported Pd catalyst. A wide range of unactivated benzoic acids could cross-couple an array of aryl iodides in moderate to excellent yields. The choice of HFIP as a solvent is crucial to realizing the mild C-H arylation, and the beneficial effect of the ligand on the reaction likely stems from the accelerated C-H activation process and the improved catalyst lifetime. PMID- 26135736 TI - Motivation and Social Cognition in Patients with Schizophrenia. AB - Social cognition, referring to one's ability to perceive and process social cues, is an important domain in schizophrenia. Numerous studies have demonstrated that patients with schizophrenia have poorer performance on tests assessing social cognition relative to healthy comparison participants. However, whether variables such as motivation are related to performance on these tests in patients with schizophrenia is unclear. One thousand three-hundred and seventy-eight patients with schizophrenia completed the Facial Emotion Discrimination Task as a measure of emotional processing, a key facet of social cognition. Level of motivation was also evaluated in these patients using a derived measure from the Quality of Life Scale. The relationship between motivation and task performance was examined using bivariate correlations and logistic regression modeling, controlling for the impact of age and overall severity of psychopathology, the latter evaluated using the Positive and Negative Syndrome Scale. Motivation was positively related to performance on the social cognition test, and this relationship remained significant after controlling for potential confounding variables such as age and illness severity. Social cognition was also related to functioning, and the relationship was mediated by level of motivation. The present study found a significant relationship between motivation and performance on a test of social cognition in a large sample of patients with schizophrenia. These findings suggest that amotivation undermines task performance, or alternatively that poor social cognitive ability impedes motivation. Future studies evaluating social cognition in patients with schizophrenia should concurrently assess for variables such as effort and motivation. PMID- 26135737 TI - Assessing community readiness online: a concurrent validation study. AB - BACKGROUND: Community readiness for facilitation and uptake of interventions can impact the success of community-based prevention efforts. As currently practiced, measuring community readiness can be a resource intensive process, compromising its use in evaluating multisite community-based prevention efforts. The purpose of this study was to develop, test and validate a more efficient online version of an existing community readiness tool and identify potential problems in completing assessments. This study was conducted in the context of a complex community-based childhood obesity prevention program in South Australia. METHODS: Following pre-testing, an online version of the community readiness tool was created, wherein respondents, with detailed knowledge of their community and prevention efforts, rated their communities on five anchored rating scales (Knowledge of Efforts, Leadership, Knowledge of the Issue, Community Climate, and Resources). Respondents completed the standard, over-the-phone community readiness interview ("gold standard") and the new online survey. Paired t-test, St. Laurent's correlation coefficient and intra-class correlation (ICC) were used to determine the validity of the online tool. Contact summary forms were completed after each interview to capture interview quality. RESULTS: Twenty-five respondents completed both assessments. There was a statistically significant difference in the overall community readiness scores between the two methods (paired t-test p = 0.03); online scores were consistently higher than interview scores. St. Laurent's correlation of 0.58 (95% CI 0.42-0.73) was moderate; the ICC of 0.65 (95% CI 0.35-0.83) was good. Only for the leadership and resources dimensions was there no statistically significant difference between the scores from the two methods (p = 0.61, p = 0.08 respectively). St Laurent's correlation (r = 0.83, 95% CI 0.71-0.92) and the ICC (0.78, 95% CI 0.57-0.90) were excellent for leadership. Qualitative results from the standard interview method suggest that some respondents felt reluctant to answer questions on behalf of other community members. This may have impacted their self-selected ratings and/or responses to questions during the interview. CONCLUSIONS: Concurrent validity for the online method was supported for the Leadership dimension only. However, the online method holds promise as it reduces time and resource burden, allowing for a quicker return of results to the community to inform program planning, implementation and evaluations to improve community health. PMID- 26135738 TI - IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice. AB - BACKGROUND: Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections. AIMS: To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus) septic arthritis and sepsis in mice. METHOD: NMRI mice were treated with anakinra (IL 1Ra) daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups. RESULTS: IL 1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls. CONCLUSION: IL 1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice. PMID- 26135739 TI - Extracellular Virions: The Advance Guard of Poxvirus Infections. PMID- 26135716 TI - Hippocampal sharp wave-ripple: A cognitive biomarker for episodic memory and planning. AB - Sharp wave ripples (SPW-Rs) represent the most synchronous population pattern in the mammalian brain. Their excitatory output affects a wide area of the cortex and several subcortical nuclei. SPW-Rs occur during "off-line" states of the brain, associated with consummatory behaviors and non-REM sleep, and are influenced by numerous neurotransmitters and neuromodulators. They arise from the excitatory recurrent system of the CA3 region and the SPW-induced excitation brings about a fast network oscillation (ripple) in CA1. The spike content of SPW Rs is temporally and spatially coordinated by a consortium of interneurons to replay fragments of waking neuronal sequences in a compressed format. SPW-Rs assist in transferring this compressed hippocampal representation to distributed circuits to support memory consolidation; selective disruption of SPW-Rs interferes with memory. Recently acquired and pre-existing information are combined during SPW-R replay to influence decisions, plan actions and, potentially, allow for creative thoughts. In addition to the widely studied contribution to memory, SPW-Rs may also affect endocrine function via activation of hypothalamic circuits. Alteration of the physiological mechanisms supporting SPW-Rs leads to their pathological conversion, "p-ripples," which are a marker of epileptogenic tissue and can be observed in rodent models of schizophrenia and Alzheimer's Disease. Mechanisms for SPW-R genesis and function are discussed in this review. PMID- 26135740 TI - Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal. AB - BACKGROUND: Plasma is commonly used for vitamin K antagonist (VKA) reversal, but observational studies suggest that it is associated with transfusion-related adverse reactions (e.g., volume overload). However, this issue has not previously been addressed in a randomized controlled trial (RCT). STUDY DESIGN AND METHODS: Factors associated with volume overload were examined using data from two Phase IIIb RCTs comparing plasma with four-factor prothrombin complex concentrate (4F PCC, Beriplex/Kcentra, CSL Behring) for urgent VKA reversal. VKA-treated patients with major bleeding (NCT00708435) or requiring an urgent surgical or invasive procedure (NCT00803101) were randomly assigned (1:1) to receive either plasma or 4F-PCC, concomitant with vitamin K. Adverse events (AEs) and serious AEs were prospectively captured up to Day 10 and 45, respectively. Volume overload predictors were evaluated on a univariate and multivariate basis. RESULTS: A total of 388 patients (4F-PCC, n = 191; plasma, n = 197) were enrolled. Volume overload occurred in 34 (9%) patients (4F-PCC, n = 9; plasma, n = 25). In univariate analyses, use of plasma (vs. 4F-PCC), use of nonstudy plasma and/or platelets, race, history of congestive heart failure (CHF), and history of renal disease were associated with volume overload. In multivariate analyses, use of plasma (vs. 4F-PCC), history of CHF, and history of renal disease were independent volume overload predictors. In an additional analysis restricted to volume overload events recorded up to Day 7, only use of plasma (vs. 4F-PCC) was an independent volume overload predictor. CONCLUSIONS: After adjusting for other potential risk factors, plasma use was independently associated with a greater risk of volume overload than 4F-PCC in patients requiring urgent VKA reversal. PMID- 26135742 TI - Exercise during pregnancy. A narrative review asking: what do we know? AB - Although there is no consensus as to whether exercise is beneficial during pregnancy, most studies report it poses no risk to either the mother or the fetus, and many suggest it to be beneficial to both. This review, which examines the evidence available, also reveals the many differences in study design followed, the type of exercise undertaken and the variables measured, which make it difficult to compare results. Advances in our understanding of the effects of exercise during pregnancy might best be made by undertaking randomised clinical trials with standardised protocols. However, most of the studies examining the relationship between exercise and pregnancy report no complications on maternal or fetal well-being. This is also in line with recent review studies advising that the pregnant population without obstetric contraindications should be encouraged to exercise during pregnancy. Therefore, the results of the present review stimulate those responsible for the healthcare of the pregnant woman to recommend moderate exercise throughout pregnancy without risk to maternal and fetal health. PMID- 26135741 TI - Chronic Dietary Administration of the Glycolytic Inhibitor 2-Deoxy-D-Glucose (2 DG) Inhibits the Growth of Implanted Ehrlich's Ascites Tumor in Mice. AB - BACKGROUND: Dietary energy restriction (DER) has been well established as a potent anticancer strategy. Non-adoption of restricted diet for an extended period has limited its practical implementation in humans with a compelling need to develop agents that mimic effects similar to DER, without reduction in actual dietary intake. Glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has recently been shown to possess potential as an energy restriction mimetic agent (ERMA). In the present study we evaluated the effect of dietary 2-DG administration on a mouse tumor model, with a focus on several potential mechanisms that may account for the inhibition of tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: Swiss albino strain 'A' mice were administered with 0.2% and 0.4% w/v 2-DG in drinking water for 3 months prior to tumor implantation (Ehrlich's ascites carcinoma; EAC) and continued till the termination of the study with no adverse effects on general physiology and animal growth. Dietary 2-DG significantly reduced the tumor incidence, delayed the onset, and compromised the tumor growth along with enhanced survival. We observed reduced blood glucose and serum insulin levels along with decreased proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine positive (BrdU+) tumor cells in 2-DG fed mice. Also, reduced levels of certain key players of metabolic pathways such as phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt and hypoxia inducible factor-1 alpha (HIF 1alpha) were also noted in tumors of 2-DG fed mice. Further, decrease in CD4+/CD8+ ratio and T-regulatory cells observed in 2-DG fed mice suggested enhanced antitumor immunity and T cell effector function. CONCLUSION/SIGNIFICANCE: These results strongly suggest that dietary 2-DG administration in mice, at doses easily achievable in humans, suitably modulates several pleotrophic factors mimicking DER and inhibits tumorigenesis, emphasizing the use of ERMAs as a promising cancer preventive strategy. PMID- 26135743 TI - The Developmental Emergence of the Mental Time-Line: Spatial and Numerical Distortion of Time Judgement. AB - The perception of time is susceptible to distortion by factors such as attention, emotion, or even the physical properties of the stimulus to be timed. In adults, there is now evidence for a left-right spatial representation of time or "mental time-line", in which short durations map to the left side of space, whereas long durations map to the right. We investigated the developmental trajectory of the mental time-line, by examining how spatial and numerical stimulus properties affect temporal bisection judgements in 3 groups of children (5, 8 or 10 year olds), as well as in adults. In contrast to previous developmental studies of the spatial representation of time, we manipulated spatial position (left-right) rather than spatial magnitude (distance) so as to pinpoint the age at which the mental time-line begins to influence the judgement of time. In addition, we manipulated spatial position symbolically, either directly, using left- or right pointing arrows, or indirectly, using low (1) or high (9) digits. In adults and older children (10 year olds), the rightward arrow and the higher digit were judged to last longer. However, time judgements were unaffected by arrow direction and digits in the younger children. Therefore, the temporal distortions induced by symbolic representations of space (arrows) or number (digits) emerged with development, suggesting that the mental time-line is not derived from a primitive spatial representation of time but, rather, is the fruit of learning and is acquired around the age of 8-10 years old. PMID- 26135744 TI - Molecular Cloning and mRNA Expression of Heat Shock Protein Genes and Their Response to Cadmium Stress in the Grasshopper Oxya chinensis. AB - Heat shock proteins (Hsps) are highly conserved molecular chaperones that are synthesized in response to stress. In this study, we cloned the full-length sequences of the Grp78 (glucose-regulated protein 78), Hsp70, Hsp90, and Hsp40 genes from the Chinese rice grasshopper Oxya chinensis. The full-length cDNA sequences of OcGrp78, OcHsp70, OcHsp90, and OcHsp40 contain open reading frames of 1947, 1920, 2172, and 1042 bp that encode proteins of 649, 640, 724, and 347 amino acids, respectively. Fluorescent real-time quantitative PCR (RT-qPCR) was performed to quantify the relative transcript levels of these Hsp genes in different tissues and developmental stages. The mRNAs encoding these four Hsp genes were present at all developmental stages and in all tissues examined but were expressed at varying levels. Additionally, we investigated the mRNA expression profiles of these four Hsps in O. chinensis subjected to Cadmium (Cd) stress. OcGrp78, OcHsp70, OcHsp90, and OcHsp40 mRNA expression was induced under acute Cd stress; the levels reached a maximum within a short time (6 h), were reduced significantly at 12 h, and were lowered to or below control levels by 48 h. Regarding induction efficiency, OcHsp70 was the most sensitive gene to acute Cd stress. Chronic Cd exposure showed that dietary Cd treatment induced increased OcGrp78, OcHsp90, and OcHsp40 expression. However, dietary Cd induced a significant reduction of OcHsp70 expression. In the period tested, no significant difference in the mortality of the grasshoppers was observed. Our results suggest that these four Hsps genes, especially OcHsp70, are sensitive to acute Cd stress and could be used as molecular markers for toxicology studies. However, our results also indicate that OcHsp70 is not suitable for use as a molecular marker of chronic Cd contamination. PMID- 26135745 TI - Best Friend Influence Over Adolescent Problem Behaviors: Socialized by the Satisfied. AB - The present study was designed to examine best friend influence over alcohol intoxication and truancy as a function of relative perceptions of friendship satisfaction. The participants were 700 adolescents (306 boys, 394 girls) who were involved in same-sex best friendships that were stable from one academic year to the next. Participants completed self-report measures of alcohol intoxication frequency and truancy at 1-year intervals. Each member of each friendship dyad also rated his or her satisfaction with the relationship. At the outset, participants were in secondary school (approximately 13-14 years old) or high school (approximately 16-17 years old). More satisfied friends had greater influence than less satisfied friends over changes in intoxication frequency and truancy. Problem behaviors of less satisfied friends increased over time if the more satisfied friend reported relatively higher, but not relatively lower, initial levels of drinking or truancy. The results support the hypothesis that adolescent friends are not similarly influential. The power to socialize, for better and for worse, rests with the partner who has a more positive perception of the relationship. PMID- 26135746 TI - Total Synthesis of 4,5-Didehydroguadiscine: A Potent Melanogenesis Inhibitor from the Brazilian Medicinal Herb, Hornschuchia obliqua. AB - The first total synthesis of the 7,7-dimethylaporphinoid, 4,5-didehydroguadiscine (6), originally isolated from the stems and roots of Hornschuchia oblique (Annonaceae), was achieved by the condensation of homopiperonylamine (7) with an alpha,alpha-dimethylphenylacetic acid derivative (8) and subsequent Pschorr reaction of the resulting benzylisoquinoline intermediate (22). The reported (13)C NMR data were partially revised on the basis of the analysis of HMBC spectra measured under different conditions. The melanogenesis inhibitory activity (IC50 = 4.7 MUM) of 6 was 40 times stronger than that of arbutin (174 MUM), which was used as reference standard. Furthermore, 6 was the most potent natural melanogenesis inhibitor within this class of compounds. PMID- 26135752 TI - In vivo evidence by magnetic resonance volumetry of a gestational age dependent response to tracheal occlusion for congenital diaphragmatic hernia. AB - OBJECTIVE: We aimed to assess in vivo changes in lung and liver volumes in fetuses with isolated congenital diaphragmatic hernia, either expectantly managed or treated in utero. METHOD: This is a secondary analysis of prospectively collected data at two fetal therapy centers. We used archived magnetic resonance images of fetuses taken >=7 days apart, creating paired observations in 20 expectantly managed cases, 41 with a second magnetic resonance prior to balloon reversal and 64 after balloon removal. We measured observed to expected total fetal lung volume (O/E TFLV) and liver-to-thoracic volume ratio. We calculated changes in volume as compared with the initial measurement and its rate as a function of gestational age (GA) at occlusion. RESULTS: The liver-to-thoracic volume ratio did not change in either group. In expectantly managed fetuses, O/E TFLV did not increase with gestation. In fetuses undergoing tracheal occlusion, the measured increase in volume was 2.6 times larger with balloon in place as compared with that after its removal. GA at tracheal occlusion was an independent predictor of the O/E TFLV. The net rate seems to initially increase and plateau at a maximum of 1.5% per week by 35 to 45 days after occlusion. CONCLUSIONS: Tracheal occlusion induces a net increase in volume, its magnitude essentially dependent on the GA at occlusion. PMID- 26135753 TI - Phenolic composition of "bud extracts" of Ribes nigrum L., Rosa canina L. and Tilia tomentosa M. AB - Liquid preparations such as tinctures and "bud extracts" are typical products widely used in European countries but which have been poorly studied to date. Our research was focused on obtaining a phytochemical characterization of secondary metabolites of black currant, dog rose and silver linden bud extracts and evaluating the changes of selected chemical markers over time. 16 different preparations have been analyzed by the use of HPLC-DAD-MS. Several flavonols were identified in black currant samples including quercetin derivatives (6.7 30.4mg/L). Also hydroxycinnamic acids, mainly p-coumaric acid derivatives (4.1 38.9mg/L) were identified. Flavonols such as glycosides of quercetin and kaempferol, hydroxycinnamic acids, and ellagitannins were detected in dog rose samples, with gallotannins being the main components (up to 1.7g/L). The Tilia tomentosa extracts contained flavonols (quercetin, kaempferol, apigenin derivatives) as principal components with the exception of a single commercial extract with hydroxycinnamic acids as the most abundant metabolites. In this study, without applying accelerated ageing protocols, the stability over time of these liquid preparations was evaluated for up to 10 months and demonstrated negligible variations. PMID- 26135751 TI - Footprinting analysis of interactions between the largest eukaryotic RNase P/MRP protein Pop1 and RNase P/MRP RNA components. AB - Ribonuclease (RNase) P and RNase MRP are closely related catalytic ribonucleoproteins involved in the metabolism of a wide range of RNA molecules, including tRNA, rRNA, and some mRNAs. The catalytic RNA component of eukaryotic RNase P retains the core elements of the bacterial RNase P ribozyme; however, the peripheral RNA elements responsible for the stabilization of the global architecture are largely absent in the eukaryotic enzyme. At the same time, the protein makeup of eukaryotic RNase P is considerably more complex than that of the bacterial RNase P. RNase MRP, an essential and ubiquitous eukaryotic enzyme, has a structural organization resembling that of eukaryotic RNase P, and the two enzymes share most of their protein components. Here, we present the results of the analysis of interactions between the largest protein component of yeast RNases P/MRP, Pop1, and the RNA moieties of the enzymes, discuss structural implications of the results, and suggest that Pop1 plays the role of a scaffold for the stabilization of the global architecture of eukaryotic RNase P RNA, substituting for the network of RNA-RNA tertiary interactions that maintain the global RNA structure in bacterial RNase P. PMID- 26135754 TI - Expectant management of preterm preeclampsia in Indonesia and the role of steroids. AB - OBJECTIVE: To present the outcome of expectant management of preterm preeclampsia in Indonesia, and the effect of ongoing treatment with methylprednisolone (MP) on maternal and perinatal outcome. MATERIAL AND METHODS: Prospective RCT on 48 patients with early-onset preeclampsia. Following the administration of dexamethasone for fetal lung maturation, patients were randomized to receive 25 mg MP group IV for the first week, decreasing to 12.5 mg during 2nd week and continued till birth, or matching IV placebo treatment (PL group). Prolongation of entry to delivery interval served as primary outcome measurement. RESULTS: The average time gained with expectant management was almost 14 days. However, there was no difference of mean time interval between entry to delivery between the PL (13.8 days) and MP (13.7 days) groups. Antenatal ongoing treatment with IV MP also did not improve maternal and/or perinatal outcome and might be associated with a higher risk for severe maternal infections--in particular tuberculosis. CONCLUSION: Expectant management of preterm preeclampsia is a realistic option in a major Indonesian perinatal referral center. Steroids (outside the use for fetal lung maturation) should not be used in the expectant management of preterm preeclampsia in Indonesia. PMID- 26135755 TI - Fetal intra-abdominal cysts: accuracy and predictive value of prenatal ultrasound. AB - OBJECTIVE: The finding of a fetal intra-abdominal cyst is relatively common and it can be due to a wide variety of clinical conditions. The aims of this study were to determine the accuracy of the prenatal ultrasound (US) in identifying the etiology of fetal intra-abdominal cysts and to describe the neonatal outcomes. METHODS: All cases of fetal intra-abdominal cystic lesion referred to our center between 2004 and 2012 were reviewed. Cysts of urinary system origin were excluded. Prenatal and postnatal data were collected. Our cohort was divided into subgroups according to the prenatal suspected origin of the lesion (ovarian, mesenteric, gastro-intestinal and other locations). For each subgroup, sensitivity, specificity, positive predictive value, false-positive rate and accuracy of fetal US were calculated. RESULTS: In total 47 fetuses (10/37 M/F) were identified. The mean gestational age at the time of diagnosis was 33 +/- 4.9 weeks. Our cohort comprised of 25 ovarian cysts (10 simplex and 15 complex), 3 GI duplication, 6 mesenteric lesions, 4 meconium pseudocyst and 9 lesions of other origin. Surgery was performed in 38 cases (81%) at birth. The prenatally established diagnosis was exactly concordant with post-natal findings in 34 cases (72.3%). Sensitivity, specificity, positive predictive value and false-positive rate of US were 88.1%, 95.5%, 71% and 5.4%, respectively. Long-term outcome was good in almost 90% of the cases. CONCLUSIONS: The etiology of fetal intra abdominal cysts can be prenatally diagnosed in about 70% cases. Despite the high risk of surgery at birth, the long-term outcome was good in most of the cases. PMID- 26135756 TI - Risk factors for failed vacuum extraction and associated complications in term newborn infants: a population-based cohort study. AB - OBJECTIVE: The aims of the present study were to investigate risk factors for failed vacuum extraction (VE), and to compare neonatal complications among infants delivered by failed VE with those delivered by successful VE. METHODS: Population-based study including all women (and their newborn infants) with singleton pregnancy who gave birth at term by failed VE (n = 4747) or successful VE (n = 83 671) in Sweden between 1999 and 2010. Failed VE was defined as VE followed by an emergency cesarean section (ECS), forceps, or both forceps and ECS. We used logistic regression to examine the association between failed VE in relation to intracranial hemorrhage, subgaleal hemorrhage, Apgar scores <7 at 5 min, and neonatal convulsions. RESULTS: Risk factors for failed VE included occipito posterior position, mid-pelvic fetal station, high birth weight, short maternal stature, epidural analgesia, and induction of labor. Compared with infants born after a successful VE, those delivered by failed VE had a higher risk of subgaleal hemorrhage OR 7.3 CI (5.5-9.7), convulsions OR 1.9 CI (1.4 2.7), and low Apgar OR 2.6 CI (2.3-3.0), but not of ICH. CONCLUSION: Failed VE is associated with neonatal complications. Fetal head position and station should be carefully assessed prior to the extraction. PMID- 26135757 TI - Fetal adrenal gland volume and preterm birth: a prospective third-trimester screening evaluation. AB - OBJECTIVE: Given the importance of the fetal adrenal gland in producing hormones critical to labor, we sought to evaluate whether sonographic three-dimensional measurements of the adrenal gland are a useful screening tool for spontaneous preterm birth (SPTB). METHOD: We prospectively screened 128 non-anomalous singletons from 24 to 36 weeks' gestation with volumetric measurements of the fetal adrenal gland at their indicated antenatal sonogram. Labor and delivery outcomes were assessed and compared with respect to adrenal volume. RESULTS: When corrected for estimated fetal weight, the 11 women (9%) who delivered following SPTB had smaller adrenals than those who did not, 0.33 cm(3)/kg compared with 0.57 cm(3)/kg, respectively (p = 0.006). There was no difference in volumes between those who delivered by SPTB within 7 days or greater than 14 days from measurement (0.34 cm(3)/kg versus 0.33 cm(3)/kg, p = 0.79). Among women at increased risk of SPTB, those with SPTB had smaller adrenals than those who did not: 0.32 cm(3)/kg versus 0.53 cm(3)/kg, p = 0.06. CONCLUSION: We found fetal adrenal glands significantly smaller for those delivering preterm. Given the prior literature and our asymptomatic population, our data support multiple pathways leading to SPTB. PMID- 26135758 TI - Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia. AB - INTRODUCTION: Preeclampsia is one of the major causes of maternal and neonatal mortality. During pregnancy, the immune system must maintain the tolerance to the fetus, thus changes in the cytokine balance may result in a disturbed pregnancy. T helper cells play an important role in modulation of the immune system and are involved in this cytokine balance. OBJECTIVE: Many studies have been performed to study the T cell composition in different compartments during pregnancy, although this is the first study in which T cells are evaluated in umbilical cord blood. STUDY DESIGN: Intracellular expression of INF-gamma, IL-17, IL-4 and forkhead foxP3 in CD4+ T cells was evaluated in umbilical blood from healthy pregnant and preeclamptic women using a flow cytometer. RESULTS: Th2 and Treg cells levels were significantly diminished in preeclamptic compared to the healthy women, but no difference in Th1 and Th17 levels were found between both groups. CONCLUSIONS: Our data suggest that the cytokine balance is broken, encouraging the development of an exacerbated inflammatory response. Our results show that there is a shift, in the Th1/Th2, and the Th17/Treg balance, favoring skewness towards a proinflammatory status in the umbilical cord blood in preeclampsia. PMID- 26135759 TI - Missed opportunities for appropriate postpartum care in women with pregestational diabetes. AB - OBJECTIVE: Our aim was to evaluate postpartum glycemic control in women with pregestational diabetes and to assess contributing factors. METHODS: Retrospective data collection from an electronic database on a cohort of Israeli women at Clalit Healthcare Services with pregestational diabetes who gave birth in 2008-2011, including data on HbA(1C), prescription fillings, and socio demographics. HbA(1C) level was assessed during a 2 year time-period, from periconception until one-year postpartum. RESULTS: There were 180 deliveries to 166 women. Compared with the periconception period, the HbA(1C) level improved significantly during the last 6 months of pregnancy (6.7% versus 6.0%, p < 0.05). However, there was rapid continuous deterioration in glycemic control in the postpartum period with median HbA(1C) = 6.9% in the first 6 months postpartum and 7.2% in the late postpartum period (p < 0.05). One-year postpartum 107 women (59.4%) had suboptimal care (defined as HbA(1C) > 7.0% or no test). In the multiple logistic regression analysis, the only significant predictor of 1-year postpartum suboptimal care was suboptimal periconception care, OR = 6.1 (95% CI 3.15-11.84, p = 0.001). CONCLUSIONS: Postpartum glycemic control deteriorated rapidly despite excellent control in most women in the last 6 month of pregnancy. More intensive and targeted intervention is needed in order to optimize postpartum care of diabetic patients. PMID- 26135760 TI - Fetal tricuspid annulus plane systolic excursion (fTAPSE) at term - association with cerebroplacental ratio, birthweight and neonatal pH. AB - OBJECTIVE: To study at term the association of the fetal tricuspid annulus plane systolic excursion (fTAPSE) with gestational age (GA), birthweight (BW), cerebroplacental ratio (CPR) and neonatal pH. METHODS: fTAPSE was evaluated in 309 fetuses in relation with GA and BW. Standardized values for fetal size using the head circumference were also studied in relation with CPR multiples of the median (MoM) and BW centile, evaluating the existence of differences in small-for gestational-age (SGA) fetuses and in fetuses with low CPR. In addition, in a subgroup of 286 fetuses, standardized fTAPSE was evaluated according to neonatal venous and arterial pH. RESULTS: fTAPSE correlated with BW but not with GA. In addition, although standardized values correlated with BW centile and CPR MoM, they did not differ either in SGA fetuses or in fetuses with abnormal CPR. Finally, no correlation was found between fTAPSE and neonatal pH. CONCLUSIONS: In the term fetus, fTAPSE changes with absolute fetal weight, reflecting the physiological variations occurring with fetal size. However, it is very scarcely influenced by fetal Doppler or BW centile and does not associate with neonatal pH. These data support the idea that the fetal heart is not a valuable target in the study of late-onset growth restriction. PMID- 26135761 TI - Fetal growth impairment after first-trimester chorionic villus sampling: a case control study. AB - OBJECTIVE: The objective of this study is to test if chorionic villus sampling (CVS) is associated with fetal growth impairment, after controlling for maternal and fetal factors. STUDY DESIGN: Case-control study of singleton fetuses whose mothers had undergone CVS (N = 442) and 2969 controls. The primary outcomes were the prevalence of birthweight < 10th centile and birthweight <3rd centile; the prevalence of preeclampsia was the secondary outcome. Tested predictors in logistic regression analysis included CVS, free beta-hCG MoMs, PAPP-A MoMs, first trimester mean uterine artery pulsatility index (PI) z-scores, maternal height, BMI, age, and smoking. RESULTS: The proportion of newborns with birthweight <10th centile (7.9 versus 6.2%), and <3rd centile (1.6 versus 1.1%) did not differ between the two groups. Maternal age, smoking during pregnancy, PAPP-A MoMs, and mean first-trimester uterine PI z-score were significant predictors for these outcomes. Although the prevalence of preeclampsia was higher in the CVS group (3.2 versus 1.3%, OR 2.62, 95% CI 1.41-4.89), the association was abolished in the regression analysis, in which maternal body mass index, free b-hCG levels, and mean first-trimester uterine PI z-score were the only significant predictors. CONCLUSIONS: CVS is not associated with fetal growth impairment, possibly because the resulting mechanical disruption is compensated by the developing placenta, without significantly impairing its function. PMID- 26135762 TI - Does epidural analgesia play a role in postpartum urinary incontinence? Medium term results from a case-control study. AB - OBJECTIVE: To evaluate the medium-term effect of epidural analgesia (EA) on the possible onset of postpartum urinary incontinence (PUI). METHODS: We performed a single-centre, retrospective case-control study. At 8-week postpartum, we recruited a cohort of women who had term singleton pregnancy and foetus in cephalic presentation, and divided in six groups: (1) vaginal delivery without episiotomy, without EA; (2) vaginal delivery without episiotomy, with EA; (3) vaginal delivery with episiotomy, without EA; (4) vaginal delivery with episiotomy, with EA; (5) emergency caesarean section without previous EA during labour and (6) emergency caesarean section with previous EA during labour. For each woman, we recorded age, Body Mass Index (BMI) and the result of the following questionnaire for urinary incontinence: International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Incontinence Impact Questionnaire-7 (IIQ-7) and Urogenital Distress Inventory-6 (UDI-6). Subsequently, we compared group 1 versus group 2, group 3 versus group 4 and group 5 versus group 6. RESULTS: We did not evidence any significant difference for age, BMI and incontinence scores between groups 1 and 2, 3 and 4, and 5 and 6. CONCLUSIONS: EA did not affect the onset of PUI in medium-term, regardless the mode of delivery. PMID- 26135763 TI - Is the risk of obstetric anal sphincter injuries increased in vaginal twin deliveries? AB - OBJECTIVE: Vaginal twin deliveries have a higher rate of intrapartum interventions. We aimed to determine whether these characteristics are associated with an increased rate of obstetric anal sphincter injuries compared with singleton. STUDY DESIGN: Retrospective study of all twin pregnancies undergoing vaginal delivery trial was conducted from January 2000-September 2014. Sphincter injury rate compared with all concurrent singleton vaginal deliveries. Multivariable analysis was used to determine twin delivery association with sphincter injuries while adjusting for confounders. RESULTS: About 717 eligible twin deliveries. Outcome was compared with 33 886 singleton deliveries. Twin pregnancies characterized by a higher rate of nulliparity (54.8% versus 49.5%, p = 0.005), labor induction (42.7% versus 29.1%, p < 0.001), and instrumental deliveries (27.5% versus 16.7%, p < 0.001), lower gestational (34.6 +/- 3.3 versus 38.8 +/- 2.3, p < 0.001), and lower birth weight. Total breech extraction was performed in 29.0% (208/717) of twin deliveries. Overall obstetric sphincter injury rate was significantly lower in the twins group (2.8% versus 4.4%, p = 0.03, OR = 0.6, 95% CI 0.4-0.9), due to lower rate of 3rd degree tears in twins versus singletons (2.2% versus 4.0%, p = 0.02), rate of 4th degree tears similar among the groups (0.6% versus 0.4%, p = 0.5). In multivariable analysis, sphincter injuries were associated with nulliparity (OR = 3.9, 95% CI 3.4-4.5), forceps (OR = 6.8, 95% CI 5.8-7.8), vacuum (OR = 2.9, 95% CI 2.5-3.3), earlier gestational age (OR = 0.2, 95% CI 0.1-0.3), episiotomy (OR = 0.8, 95% CI 0.7 0.9), and birth weight over 3500 g (OR = 1.8, 95% CI 1.6-2.0). However, the association between twins (versus singletons) deliveries and sphincter injuries was lost after adjustment for delivery gestational age (OR = 0.7, 95% CI 0.4 1.2). CONCLUSION: Despite a higher rate of intrapartum interventions, the rate of sphincter injuries is lower in twins versus singleton deliveries, mainly due to a lower gestational age at delivery. PMID- 26135764 TI - Quantifying force application to a newborn manikin during simulated cardiopulmonary resuscitation. AB - OBJECTIVE: To assess utility of the FingerTPSTM system in measuring chest compression (CC) rate and force. METHODS: Five minutes of CC was performed in a neonatal manikin without (n = 29) and with (n = 30) a metronome. The FingerTPSTM force (lbs.) was compared to pressure (mmHg) in a 50-mL normal-saline bag inside the manikin. FingerTPSTM CC rate and the time until a 20% decline from baseline force and pressure were calculated. RESULTS: The normal-saline pressure declined earlier than the FingerTPSTM force. Metronome use did not influence CC rate, force or pressure. CONCLUSIONS: The FingerTPSTM can be used to measure CC rate and force. PMID- 26135766 TI - Twins in Ancient Greece: a synopsis. AB - This brief outline associates twins with several aspects of life in Ancient Greece. In Greek mythology twins caused ambivalent reactions and were believed to have ambivalent feelings for each other. Very often, they were viewed as the representatives of the dualistic nature of the universe. Heteropaternal superfecundation, which dominates in ancient myths, explains on one hand, the god like qualities and, on the other hand, the mortal nature of many twins. An assumption is presented that legends referring to twins might reflect the territorial expansions of Ancient Greeks in Northern Mediterranean, around the Black Sea, in Asia Minor, as well as North East Africa. In conclusion, in Greek antiquity, twins have been used as transitional figures between myth and reality. PMID- 26135765 TI - Role of presepsin in the diagnosis of late-onset neonatal sepsis in preterm infants. AB - OBJECTIVE: One of the most challenging aspects in the management of neonates with late-onset neonatal sepsis (LOS) is to make the diagnosis. Presepsin is a novel and promising marker of sepsis. The aim of this study was to assess the role of presepsin in the diagnosis of LOS in preterm infants. METHODS: Forty-two premature newborns <=32 weeks gestational age with a diagnosis of LOS were prospectively involved in the study. Forty gestational and postnatal age-matched infants without sepsis served as controls. Levels of presepsin, C-reactive protein, and procalcitonin were measured at enrollment and on the third and seventh days of sepsis. RESULTS: Initial presepsin levels in the LOS group were significantly higher than in the control group (1024 pg/mL, min-max: 295-8202; versus 530 pg/mL, min-max: 190-782; p < 0.0001). The area under the receiver operating curve for presepsin was 0.864. A presepsin value of 800.5 pg/mL was established as a cut-off value, with 67% sensitivity and 100% specificity. Presepsin levels gradually decreased during treatment. CONCLUSION: Presepsin can be used as a reliable biomarker for LOS and treatment response in preterm infants. However, we could not demonstrate the efficacy of presepsin for the detection of disease severity or prognosis. PMID- 26135767 TI - The cellular immunity and oxidative stress markers in early pregnancy loss. AB - OBJECTIVE: We investigated whether changes in cellular immunity and oxidative stress in pregnancy have any association with spontaneous miscarriage. MATERIAL AND METHODS: Circulating adenosine deaminase (ADA) activity as a marker of cellular immunity and malondialdehyde (MDA) and catalase (CAT), glutathione peroxidase (GPx) as markers of T lymphocyte activation and parameters of oxidative stress and antioxidant defense were compared between 40 women with early pregnancy loss and another 40 women with ungoing healthy pregnancy. RESULTS: Women with miscarriage had higher serum ADA and GPx levels when compared with women with normal pregnancy (p = 0.034 and p < 0.001, respectively). Although serum MDA level was slightly higher in women with miscarriage, the difference was not significant (p = 0.083). CAT levels were alike in both groups. CONCLUSION: We have demonstrated an increased cellular immunity and perhaps a compensated oxidative stress related to increased antioxidant activation in women with early spontaneous pregnancy loss. PMID- 26135768 TI - Biomarkers in neonatology: the new "omics" of bronchopulmonary dysplasia. AB - Bronchopulmonary dysplasia (BPD) is a complex disorder resulting from gene environmental interactions. An improved understanding of the pathogenesis of this most common chronic lung disease in infants has been made by utilizing animal models and correlating with human data. Currently, while some (vitamin A, caffeine) pharmacotherapeutic options are being utilized to ameliorate this condition, there is still no specific or effective treatment for BPD. It would be helpful for prognostication and targeted potential novel therapeutic strategies to identify those babies accurately who are at risk for developing this disease. A reliable biomarker would have the capacity to be detected in the initial phase of the disease, to allow early interventions to avoid or minimize the detrimental effects of the disease. This review will focus on human studies performed with the "omic" techniques, specifically genomics, epigenomics, microbiomics, transciptomics, proteomics and metabolomics, and summarize the information available in the literature, as it pertains to biomarker identification for BPD. Using "omics" technologies, investigators have reported markers that have the potential to be used as biomarkers of BPD: SPOCK2, VEGF -624C > G, VEGF -460T > C, mast cells specific markers, miR-219 pathway, miR-152, -30a-3p, -133b, -206, 7, lactate, taurine, trimethylamine-N-oxide, gluconate, myoinositol and alterations in surfactant lipid profile. PMID- 26135769 TI - Prediction of lethal pulmonary hypoplasia by means fetal lung volume in skeletal dysplasias: a three-dimensional ultrasound assessment. AB - OBJECTIVE: The aim of this study was to assess the capacity of three-dimensional ultrasound (3DUS) for predicting lethality in fetuses with skeletal dysplasia. METHODS: Twenty-four fetuses between 20 and 32 weeks of gestation were assessed. Bilateral lung volume scans were performed three times in each fetus during one ultrasound session. The virtual organ computer-aided analysis method was used to obtain a sequence of six sections of each lung around a fixed axis, and a rotation angle of 30 degrees was adopted. Fetal lung volume measurements were analyzed according to the reference range. After birth, lung hypoplasia was diagnosed considering clinical and radiological criteria. RESULTS: Of all cases of skeletal dysplasia, 18 (75%) were lethal. Among the lethal cases, after postnatal diagnosis, four were osteogenesis imperfecta type II, three were thanatophoric dysplasia and two were campomelic dysplasia. The remaining nine cases remained without a definitive diagnosis. The accuracy of 3DUS in predicting lethality in fetuses with skeletal dysplasia was high, with a sensitivity of 83.3%, specificity of 100%, positive predictive value of 100% and negative predictive value of 66.7%. The kappa index of 0.174 showed a good agreement between the possibility of lethality when the 3DUS volume measurement was altered and real lethality after birth (p < 0.001). CONCLUSION: This study suggests that the 3DUS lung volume measurement is a good predictor of lethal pulmonary hypoplasia in fetuses with skeletal dysplasia, with high accuracy. PMID- 26135770 TI - Ischemia-modified albumin as an oxidative stress biomarker in early pregnancy loss. AB - BACKGROUND/AIMS: This study aimed to determine the association between early pregnancy loss and serum ischemia-modified albumin (IMA) concentrations. METHODS: Serum samples of 180 women that included healthy pregnant women, women admitted for termination of pregnancy due to the absence of fetal cardiac activity or absence of fetal pole on ultrasonographic examination, and healthy non-pregnant women attending for gynecological examination. Each group included 60 patients. Serum concentrations of IMA were compared among the groups, and the correlations with patients' age, gravidity, BMI, gestational age and total serum albumin concentrations were calculated. RESULTS: When the groups were compared with respect to IMA concentrations, the group with early pregnancy loss was found to have significantly higher IMA concentrations (p < 0.001). An IMA threshold of >163 ng/mL had a sensitivity of 75%, specificity of 55% to discriminate between healthy pregnant patients and patients with early pregnancy loss in first trimester. CONCLUSION: Our findings support the theory that possible oxidative stress, a more hypoxic environment and defective placentation lead to increased serum IMA concentrations. These findings may help to shed light on the complicated pathogenesis of early pregnancy loss. PMID- 26135771 TI - Detection of abnormalities in ultrasound lung image using multi-level RVM classification. AB - The classification of abnormalities in ultrasound images is the monitoring tool of fluid to air passage in the lung. In this study, the adaptive median filtering technique is employed for the preprocessing step. The preprocessed image is then extracted the features by the convoluted local tetra pattern, histogram of oriented gradient, Haralick feature extraction and the complete local binary pattern. The extracted features are selected by applying particle swarm optimization and differential evolution feature selection. In the final stage, classifiers namely relevance vector machine (RVM), and multi-level RVM are employed to perform classification of the lung diseases. The diseases respiratory distress syndrome (RDS), transient tachypnea of the new born, meconium aspiration syndrome, pneumothorax, bronchiolitis, pneumonia, and lung cancer are used for training and testing. The experimental analysis exhibits better accuracy, sensitivity, specificity, pixel count and fitness value than the other existing methods. The classification accuracy of above 90% is accomplished by multi-level RVM classifier. The system has been tested with a number of ultrasound lung images and has achieved satisfactory results in classifying the lung diseases. PMID- 26135772 TI - The outcome of pregnancy with new onset proteinuria without hypertension: retrospective observational study. AB - OBJECTIVE: The aim of this study was to evaluate preeclampsia progression of isolated proteinuria and associations with pregnancy outcome. METHOD: We performed a retrospective analysis in patients who were hospitalized for evaluation of new onset proteinuria without hypertension after 20 weeks of gestation between January 2012 and January 2014. One hundred fifty-seven patients who met the inclusion criteria were enrolled the study. RESULTS: After detection of new onset proteinuria, 53 of 157 (33.7%) patients developed preeclampsia and the incidence of gestational proteinuria was found to be 0.33%. Twenty-four hours urine proteinuria testing results were significantly higher in preeclampsia (PE) group compared with the gestational proteinuria (GP) group (p < 0.01). Patients who developed preeclampsia delivered significantly earlier than the GP group (p < 0.01). The weights of the infants born to mothers in the PE group were significantly lower than the other group (p < 0.01). CONCLUSION: The incidence of gestational proteinuria was lower than the previous studies. Preeclampsia developed in 33% of patients with new onset proteinuria in pregnancy. In patients who developed PE had significantly higher proteinuria, lower delivery time and birth weight in their infants. Therefore, patients with new onset proteinuria should be followed-up for preeclampsia development and associated morbidities. PMID- 26135773 TI - Clamp late and maintain perfusion (CLAMP) policy: delayed cord clamping in preterm infants. AB - OBJECTIVE: Randomized controlled trials have demonstrated that delayed umbilical cord clamping (DCC) in preterm infants results in improved neonatal outcomes, including increased hematocrit, and decreased rates of intraventricular hemorrhage (IVH) and packed red blood cell transfusions. We hypothesized that implementation of a DCC policy in preterm infants would result in similarly improved outcomes, despite initial clinician resistance. STUDY DESIGN: A DCC policy (30-60 s) for singleton infants <35 weeks gestation was implemented in September 2011. We conducted a pre-test/post-test analysis of neonatal outcomes among singletons delivered between 24 0/7 weeks and 34 6/7 weeks gestation from 2009 to 2013 (2 years pre-implementation and 2 years post-implementation). The primary outcomes were rates of policy compliance and four neonatal outcomes. RESULTS: Despite multiple routes of policy dissemination, DCC was attempted in only 49% of the deliveries. In spite of this, infants delivered post-policy implementation (n = 196) had a significant decrease in IVH, significant increase in initial hematocrits, and improved temperatures compared with infants delivered pre-implementation (n = 204). CONCLUSION: After implementation of a DCC policy, preterm singleton infants had improved temperatures, increased hematocrits and a decreased prevalence of IVH without significant differences in adverse outcomes, suggesting that the benefits of DCC outweighed the risks. PMID- 26135774 TI - Comparison of non-synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as post-extubation respiratory support in preterm infants with respiratory distress syndrome: a randomized controlled trial. AB - OBJECTIVE: To determine whether post-extubation respiratory support via nsNIPPV decreases the need for mechanical ventilation (MV) compared to nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS). METHODS: In this randomized, controlled, open, prospective, single-center clinical trial, we randomly assigned preterm ventilated infants with RDS to either nsNIPPV or NCPAP after extubation. The primary outcome, extubation failure, was defined by pre-specified failure criteria in the 72 hours after extubation. RESULTS: A total of 63 preterm ventilated infants were randomized to receive either nsNIPPV (n = 31) or NCPAP (n = 32). Extubation failure occurred in six (19.3%) of nsNIPPV group compared with nine (28.12%) of NCPAP group and was statistically not significant (p = 0.55). The duration of NIV was significantly lower in nsNIPPV group as compared to NCPAP group (40.4 +/- 39.3 hours versus 111.8 +/- 116.4 hours, p = 0.003). The duration of supplementary oxygen was significantly lower in nsNIPPV versus NCPAP group (84.9 +/- 92.1 hours versus 190.1 +/- 140.5 hours, p = 0.002). The rates of BPD in nsNIPPV group (2/29, 6.9%) were significantly lower than in NCPAP group (9/28, 32.14%) (p = 0.02). CONCLUSIONS: Compared to NCPAP, nsNIPPV appears to be a feasible mode of extubation in preterm infants with significant beneficial effects of reduced duration of NIV support, supplementary oxygen and decreased rates of BPD. PMID- 26135775 TI - Professionals' views of fetal-monitoring support the development of devices to provide objective longer-term assessment of fetal wellbeing. AB - OBJECTIVE: Continuous longer-term fetal monitoring has been proposed to address limitations of current technologies in the detection of fetal compromise. We aimed to assess professionals' views regarding current fetal-monitoring techniques and proposed longer-term continuous fetal monitoring. METHODS: A questionnaire was designed and validated to assess obstetricians' and midwives' use of current fetal-monitoring techniques and their views towards continuous monitoring. 125 of 173 received responses (72% obstetricians, 28% midwives) were analysed. RESULTS: Professionals had the strongest views about supporting evidence for the most commonly employed fetal-monitoring techniques (maternal awareness of fetal movements, ultrasound assessment of fetal growth and umbilical artery Doppler). 45.1% of professionals agreed that a continuous monitoring device would be beneficial (versus 28.7% who disagreed); this perceived benefit was not influenced by professionals' views regarding current techniques or professional background. Professionals have limited experience of continuous fetal monitoring, but most respondents believed that it would increase maternal anxiety (64.3%) and would have concerns with its use in clinical practice (81.7%). CONCLUSION: Continuous fetal monitoring would be acceptable to the majority of professionals. However, development of these technologies must be accompanied by extended examination of professionals' and women's views to determine barriers to its introduction. PMID- 26135776 TI - Does diurnal variation affect the first trimester fetal aneuploidy screening test biochemical parameters of fetuses with normal nuchal translucency? AB - OBJECTIVE: The purpose of this study was to investigate the effect of diurnal variation on biochemical results of first trimester aneuploidy screening test. METHODS: A total of 2725 singleton pregnant female, who had normal fetal nuchal translucency (NT) thickness, were included in the study during this period. Individuals were divided into two groups according to the sampling time (morning group: 09:00-11:00 am and afternoon group: 02:00-04:00 pm). Hormonal parameters (free-beta human chorionic gonadotropin [free beta-hCG] and pregnancy-associated plasma protein-A [PAPP-A] multiples of median [MoM] levels) of first trimester (11(+0)-13(+6) weeks) combined aneuploidy screening test were compared between morning and afternoon groups. RESULTS: PAPP-A MoM levels were significantly lower in the afternoon group when compared to the morning group (p = 0.001), whereas free beta-hCG MoM levels were similar in the both groups (p = 0.392). Rate of high risk for Down syndrome (Combine risk >1/300) and amniocentesis ratio were found higher in the afternoon group than morning group, but there were no difference between groups for the number of fetuses with Down syndrome. CONCLUSION: Receiving the venous blood sample for first trimester aneuploidy screening test in the afternoon causes low PAPP-A MoM levels. PMID- 26135777 TI - Maternal periconceptional alcohol consumption and the risk of neural tube defects in offspring: a meta-analysis. AB - OBJECTIVE: Several studies have been conducted to examine the association between alcohol consumption during pregnancy and risk of neural tube defects (NTDs), while the results are inconsistent. In the present study, we aimed to clarify the relationship between maternal periconceptional alcohol consumption and NTDs risk in offspring. METHODS: PubMed, Springer Link, and Elsevier databases were searched up to November, 2014. All case-control and cohort studies of maternal alcohol consumption during pregnancy with risk of NTDs were included. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) for highest versus lowest category of alcohol consumption were calculated using a fixed- or random effects model. RESULTS: The pooled ORs of maternal periconceptional alcohol consumption were 1.01 (95% CI: 0.71-1.45) for total NTDs and 1.03 (95% CI: 0.65 1.64) for NTDs subtype of spina bifida. Specifically, the pooled ORs of maternal alcohol consumption in the first trimester and binge drinking were 1.01 (95% CI: 0.71-1.43), and 1.07 (95% CI: 0.81-1.41), respectively. CONCLUSIONS: Our findings suggested no association between maternal periconceptional alcohol consumption and NTDs risk in offspring. PMID- 26135778 TI - Increased postpartum maternal complications after cesarean section compared with vaginal delivery in 225 304 Taiwanese women. AB - OBJECTIVE: To compare the short-term maternal postpartum complications associated with cesarean section (CS), vaginal delivery (VD), repeated CS and vaginal birth after cesarean section (VBAC) in a large national sample. METHODS: This was a population-based study of the Taiwan National Health Insurance Research Database (NHIRD). Outcomes include post-discharge (2 weeks) urinary tract infection (p UTI), complications of obstetrical surgical wounds (p-wound) and postpartum hemorrhage (p-hemorrhage). A logistic regression model with generalized estimating equations were utilized, and adjustments were made for maternal and hospital characteristics. RESULTS: The incidence of p-UTI was 0.79%. CS was associated with a significantly higher risk of p-UTI compared with VD (odds ratio [OR] 1.14; 95% confidence interval [CI], 1.003-1.29). The incidence of p-wound was 4.07%. CS and repeated CS were associated with a higher risk of p-wound compared with VD (OR 1.68; 95% CI, 1.28-2.21 and OR 1.64; 95% CI, 1.22-2.20, respectively). Age, maternal diseases and hospital and obstetrician volumes were associated with patient outcomes. CONCLUSIONS: Women with a delivery mode of CS have a higher risk of p-UTI and p-wound than women with VD. Maternal characteristics and hospital and obstetrician volumes may also influence postpartum outcomes. PMID- 26135779 TI - Comparison of cord blood vitamin D levels in newborns of vitamin D supplemented and unsupplemented pregnant women: a prospective, comparative study. AB - OBJECTIVE: To screen pregnant women for deficiency of 25-hydroxyvitamin D (25(OH)D) and supplement selected vitamin D deficient pregnant women with vitamin D and to compare 25(OH)D levels in cord blood between them. METHOD: Sixty pregnant women were selected as cases (vitamin D levels <30 ng/ml) and 60 unscreened pregnant women were taken as controls. Cases were supplemented with available 60,000 IU vitamin D every two weeks for eight doses or till delivery, whichever was earlier. In both the cases and controls, cord blood was collected at the time of delivery and tested for 25(OH)D levels using Biomerieux miniVIDAS. RESULT: Maximum (66.7%) pregnant women who received vitamin D supplementation had cord blood vitamin D level >30 ng/ml, while only 3.3% unsupplemented pregnant women had cord blood vitamin D level >30 ng/ml. The median cord blood vitamin D level was 36.5 ng/ml in vitamin D supplemented and 11.35 ng/ml in unsupplemented women. The mean birth weight and mean crown heel length were 3.1 +/- 0.485 kg versus 2.8 +/- 0.705 kg and 49.35 +/- 1.36 cm versus 48.67 +/- 2.12 cm, respectively. CONCLUSION: Vitamin D supplemented women had sufficient levels of 25(OH)D in cord blood at birth in maximum cases and neonates had higher birth weights and increased crown heel length. PMID- 26135780 TI - Blood loss at cesarean delivery in women on magnesium sulfate for preeclampsia. AB - OBJECTIVE: To evaluate the effect of magnesium sulfate for prevention of eclampsia on blood loss at time of cesarean delivery (CD). METHODS: We conducted an electronic based search using the following databases: MEDLINE, PUBMED and the Cochrane Library. The search terms were "magnesium sulfate", "preeclampsia" and "randomized". Inclusion criteria were randomized controlled trials of women with preeclampsia who delivered with or without magnesium sulfate therapy for seizure prophylaxis. Only trials with placebo or no treatment comparison groups were included. Primary outcome was postpartum hemorrhage. Secondary outcomes were estimated blood loss, change in hemoglobin, blood transfusion and eclampsia. RESULTS: Five trials met inclusion criteria. The incidence of postpartum hemorrhage was similar between the two groups [magnesium sulfate: 754/4482 (17%); no magnesium sulfate: 775/4427 (18%); RR 0.97, 95% CI 0.88-1.06]. There was no statistical difference between any of the other blood loss outcomes reported in the included studies. The rate of eclampsia with magnesium sulfate was significantly lower than with placebo (42/5604, 0.7%, versus 107/5600, 1.9%; RR 0.40, 95% CI 0.28-0.57). CONCLUSIONS: Magnesium sulfate does not appear to affect blood loss intrapartum and postpartum in women with preeclampsia. Magnesium sulfate, therefore, should be continued during CD, given the benefit of seizure prophylaxis without any increased risk of hemorrhage. PMID- 26135781 TI - Umbilical cord blood concentrations of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) in neonates developing hypoxic-ischemic encephalopathy. AB - OBJECTIVE: To compare ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) concentrations in umbilical cord blood of neonates who develop Sarnat stage II-III hypoxic-ischemic encephalopathy (HIE) to healthy controls, and to relate the concentrations to the severity of neurology and long-time outcomes. MATERIAL AND METHODS: Cord sera of 15 neonates with HIE II-III and 31 matched controls were analyzed for UCH-L1 and GFAP. Comparisons were performed for cord artery pH, amplitude-integrated electroencephalography (aEEG), stage of HIE, and death or sequelae up to an age of 6 years. Parametric and non-parametric statistics were used with a two-sided p < 0.05 considered significant. RESULTS: Among controls no associations between biomarker concentrations and gestational age, birthweight, length of storage of cord sera and degree of hemolysis were found. No significant differences in biomarker concentrations were found between HIE neonates and controls, and no differences were found with regard to HIE stage, cord acidemia, severity of aEEG changes, or persistent sequelae or death. CONCLUSIONS: No differences in cord blood UCH-L1 and GFAP concentrations were found between HIE neonates and controls, and no associations were found between the biomarker concentrations and the severity of disease, or whether the condition developed into a permanent or fatal injury. PMID- 26135782 TI - Placenta accreta: diagnosis, management and the molecular biology of the morbidly adherent placenta. AB - Placenta accreta is now the chief cause of postpartum hemorrhage resulting in maternal and neonatal morbidity. Prenatal diagnosis decreases blood loss at delivery and intra and post-partum complications. Ultrasound is critical for diagnosis and MRI is a complementary tool when the diagnosis is uncertain. Peripartum hysterectomy has been the standard of therapy but conservative management is increasingly being used. The etiology of accreta is due to a deficiency of maternal decidua resulting in placental invasion into the uterine myometrium. The molecular basis for the development of invasive placentation is yet to be elucidated but may involve abnormal paracrine/autocrine signaling between the deficient maternal decidua and the trophoblastic tissue. The interaction of hormones such as Relaxin which is abundant in maternal decidua and insulin-like 4, an insulin-like peptide found in placental trophoblastic tissue may play role in the formation of placenta accreta. PMID- 26135783 TI - Dexpanthenol therapy reduces lung damage in a hyperoxic lung injury in neonatal rats. AB - OBJECTIVE: Dexpanthenol (Dxp) plays a major role in cellular defense and in repair systems against oxidative stress and inflammatory response and it has not yet been evaluated in treatment of bronchopulmonary dysplasia (BPD). We tested the hypothesis that proposes whether Dxp decreases the severity of lung injury in an animal model of BPD. METHODS: Forty rat pups were divided into four groups: control, control + Dxp, hyperoxia and hyperoxia + Dxp. All animals were processed for lung histology and tissue analysis. The degree of lung inflammation, oxidative and antioxidant capacity was assessed from lung homogenates. RESULTS: Lung injury score and alveol diameter increased in the hyperoxia group (p < 0.001). Median level of malondialdehyde, total oxidant status and oxidative stress indexes was significantly higher in the hyperoxia group compared to the other groups. The median superoxide dismutase activity in the hyperoxia group was notably less than those of control + Dxp and hyperoxia + Dxp groups (p < 0.01). Similarly, lung catalase, glutathione (GSH) peroxidase and reduced GSH activities in the hyperoxia group were significantly lower than other groups. Furthermore, the hyperoxia + Dxp group had lower tumor necrosis factor-alpha and interleukin 1beta median levels compared to the hyperoxia group (p = 0.007). CONCLUSION: Dxp treatment results in less emphysematous change as well as decrease in inflammation and oxidative stress markers in an animal model of BPD. PMID- 26135784 TI - Effects of antepartum therapy for fetal alloimmune thrombocytopenia on maternal lifestyle. AB - OBJECTIVE: The objective of this study is to describe the effects of antepartum therapy for fetal alloimmune thrombocytopenia (FAIT) on lifestyle. With the goal of preventing intraventricular hemorrhage in all fetuses without cordocentesis to measure fetal platelets, empiric treatment with intravenous immune globulin (IVIG), with or without prednisone, is recommended. It is hypothesized that these treatments negatively affect women's lifestyle. This information is needed for pre-conceptual counseling and developing management strategies. METHODS: A survey was mailed to 62 women treated by one provider from 2005 to 2013 asking if they experienced side effects from IVIG and prednisone, if their lives were negatively affected, if they would plan another affected pregnancy and if they needed help managing side effects. RESULTS: Three-quarters of 32 respondents reported that the treatments negatively affected their lifestyle. Thirty-one percent of women would not plan another pregnancy due to their experience and 22% were uncertain. All women experienced adverse effects and required additional medications or healthcare resources. Ninety-four percent contacted healthcare providers for help managing side effects. CONCLUSION: The significant negative effects on the lifestyle of women treated for FAIT emphasizes the need to identify the lowest effective doses and duration of pharmacotherapy and develop management strategies. Women undergoing treatment may need additional healthcare resources, including coordination of care. PMID- 26135785 TI - Is an isolated ventricular septal defect detected before 24 weeks on ultrasound associated with fetal aneuploidy? AB - OBJECTIVE: Whether the isolated VSD (i-VSD) is associated with aneuploidy to the same degree as a more severe heart anomaly is unclear. Our objective was to determine the likelihood of aneuploidy in pregnancies at a tertiary referral center when an i-VSD is detected before 24 weeks. METHODS: A retrospective chart review of all detailed anatomy ultrasounds before 24 weeks performed at the University of Kansas Medical Center from 08/23/2006 to 06/07/2012 was conducted. A complete evaluation of the fetal heart was accomplished using gray scale and spectral/color Doppler examinations. The outcomes of each pregnancy were reviewed for any diagnoses of aneuploidy. Odds ratios were calculated. RESULTS: A total of 4078 pregnancies with complete obstetric and neonatal data were reviewed. The prevalence of an i-VSD was 2.7% (112/4078). The odds ratio of aneuploidy when an i-VSD was present was (OR: 36.0, 95% CI: 5.0, 258.1). This odds ratio remained large when either an abnormal or unknown serum screen was present. CONCLUSION: The presence of an i-VSD present before 24 weeks does increase the risk of fetal aneuploidy. Whether a normal serum screen or first trimester screen for aneuploidy negates the association of an i-VSD with aneuploidy still remains undetermined. PMID- 26135786 TI - Spontaneous regression of intralobar pulmonary sequestration during the pregnancy: report of two cases through relationships between mass and fetal biometry and review of the literature. AB - Intralobar pulmonary sequestration is a rare bronchopulmonary malformation consisting of a non-functioning lung mass that receives its arterial blood supply from systemic circulation and that does not adequately communicate with the tracheobronchial tree through a normal bronchus. These sequestrations account for 1.1-1.8% of all lung resections. Herein we present two clinical cases with a prenatal diagnosis of pulmonary sequestration using ultrasound and magnetic resonance imaging. Pulmonary images indicated a progressive decrease in the size and echogenicity of the lung mass with fetal growth, resulting in asymptomatic neonates with normal chest radiographs. We emphasize the importance of combining imaging examinations with follow-up by a multidisciplinary team working in a center specialized in maternal-fetal medicine. For the successive monitoring of the size of the lung tissue mass, we propose the calculation of the following two biometric ratios that are not yet described in the literature: mass area/head circumference and mass volume/estimated fetal weight. The second ratio was similar in both cases, a result which suggests its potential for use in estimating the probability of the spontaneous regression of intralobar pulmonary sequestration. PMID- 26135787 TI - Predictive role of transvaginal ultrasonographic measurement of cervical length at 34 weeks for late pre-term and late-term deliveries in nulliparous women. AB - OBJECTIVE: To investigate the predictive role of transvaginal ultrasonographic measurement of cervical length (CL) at 34 weeks of gestation in determining late preterm and late-term deliveries in nulliparous women. METHODS: CL was measured by transvaginal ultrasonography at 34 weeks in 318 women (singleton, nulliparous, low-risk and vertex presentation). All women were followed-up till birth and delivered at hospital. Deliveries were classifed according to gestational week as late-preterm (34(0/7) to 36(6/7) weeks), term (37(0/7) to 40(6/7) weeks) and late term (41(0/7) to 41(6/7) weeks). RESULTS: There was a significant correlation between CL at 34 weeks and gestational week at delivery (r = 0.614, p < 0.001). Receiver-operating characteristic curve analysis showed that CL measurement below 25.5 mm predicted late-preterm delivery with a sensitivity of 80.0%, specificity of 93.9%, positive predictive value (PPV) of 52.6% and negative predictive value (NPV) of 98.2%; while CL above 42.5 mm had 70.4% sensitivity, 93.5% specificity, 50.0% PPV and 97.1% NPV in prediction of late-term delivery. CONCLUSION: Measurement of CL with transvaginal ultrasonography at 34 weeks of gestation can be of beneficial in predicting the risk of late-preterm and late-term deliveries in nulliparous women. PMID- 26135788 TI - May we use ibuprofen as doses against courses in the treatment of patent ductus arteriosus in premature infants? AB - OBJECTIVE: We aimed to investigate the efficacy of ibuprofen doses in closing patent ductus arteriosus (PDA) and the possibility of reducing drug-related complications by reducing dose number. METHODS: We performed a prospective study with 60 premature infants (<=33 weeks) who were treated with enteral ibuprofen for hsPDA. Echocardiographic examinations were performed before each dose. Treatment was stopped when PDA was closed and patients were followed for reopening and complications. RESULTS: Rates of closure were 28.3%, 44.1%, 54.1%, 36.3%, 42.8% and 50.0% with the 1st, 2nd, 3rd, 4th, 5th and 6th doses. No closure was observed with 7th, 8th and 9th doses. Reopening was observed only in patients whose PDA closed with the 1st (3.3%), 2nd (1.6%) and 3rd (1.6%) doses. PDA diameters were higher in patients who required >4 doses. Complications were rare (6.6%) but unrelated with dose number. CONCLUSIONS: We conclude that it is possible to minimize ibuprofen exposure and achieve high closure rates of PDA in premature infants by performing echocardiography before each dose. PDA diameter should be used to estimate the duration of treatment. This approach is not effective in reducing complication rates and must be performed in attention to reopening especially for the first three doses. PMID- 26135789 TI - Intestinal blood flow by Doppler ultrasound: the impact of clarithromycin treatment for feeding intolerance in preterm neonates. AB - OBJECTIVE: To compare the blood flow velocities of superior mesenteric artery (SMA) before versus after clarithromycin treatment for feeding intolerance in very low-birth weight infants. METHODS: A prospective study was conducted in a group of infant <1500 g with feeding intolerance who received clarithromycin 7.5 mg/kg/dose bid. Before and at the third day of the clarithromycin therapy, SMA blood flow velocity was measured with Doppler ultrasound. RESULTS: SMA peak systolic velocity (PSV) and mean systolic velocity (MV) on the third day of the treatment was found significantly higher than the initial measurement (p = 0.013 and p = 0.027, respectively). End diastolic velocity of the SMA did not change with clarithromycin therapy (p = 0.113). There were no significant changes about pulsatility and resistive index of SMA with regard to clarithromycin therapy. CONCLUSION: Clarithromycin effects the splanchnic circulation. The rise in PSV and MV in SMA is remarkable. These results suggest that the splanchnic blood flow increases significantly after clarithromycin usage. PMID- 26135790 TI - Maternal-Fetal Medicine physicians' practice patterns for 22-week delivery management. AB - OBJECTIVE: To describe Maternal-Fetal Medicine (MFM) physicians' practice patterns for 22-week delivery management. MEHODS: Surveyed 750 randomly-sampled members of the Society of Maternal-Fetal Medicine, querying MFMs' practices and policies guiding 22-week delivery management. RESULTS: Three hundred and twenty five (43%) MFMs responded. Nearly all (87%) would offer induction. Twenty-eight percent would order steroids, and 12% would perform cesarean for a patient desiring resuscitation. Offering induction differed significantly based on the provider's practice setting, region, religious service attendance and political affiliation. In multivariable analyses, political affiliation remained a significant predictor of offering induction (p = 0.03). CONCLUSIONS: Most MFMs offer induction for PPROM at 22 weeks. A noteworthy proportion is willing to order steroids and perform cesarean. Personal beliefs and practice characteristics may contribute to these decisions. While little is known about the efficacy of these interventions at 22 weeks, some MFMs will offer obstetrical intervention if resuscitation is intended. PMID- 26135791 TI - Birth outcomes of male and female patients with infantile hypertrophic pyloric stenosis--a population-based case-control study. AB - OBJECTIVE: Most of the patients are affected by isolated infantile hypertrophic pyloric stenosis (IHPS) beyond the polygenic predisposition, the other factors in the multifactorial etiology are largely unknown. The main characteristic of IHPS is the robust male predominance, thus the aim of this study was to analyze birth outcomes in males and females whether they are different or not. METHODS: The study samples included 241 cases with IHPS, 357 matched, and 38,151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. RESULTS: The findings of this case-control study confirmed the well-known strong male excess (85.5%). The mean gestational age was somewhat longer and it is associated with a lower rate of preterm births. Mean birth weight did not show significant differences among the study groups, but the rate of low birthweight was higher in cases with IHPS. However, these differences were found only in males. Thus, intrauterine fetal growth restriction is characteristic only for male cases with IHPS. CONCLUSIONS: Our study confirmed the well-known obvious male excess of cases with IHPS, but our findings suggest some differences in birth outcomes of male and female cases. Male cases with IHPS had intrauterine fetal growth restriction while females did not. These data may indicate some differences in the pathogenesis of IHPS in males and females. PMID- 26135792 TI - Clinical risk factors for poor neonatal outcomes in umbilical cord prolapse. AB - OBJECTIVES: To clarify the clinical risk factors associated with poor neonatal outcomes due to umbilical cord prolapse (UCP). METHODS: A postal questionnaire survey was attempted in Japan. The clinical risk factors and managements associated with poor neonatal outcomes were analyzed in cases of UCP treated in Japan. RESULTS: A total of 267 cases of UCP (out of 2 037 460 total deliveries) were analyzed. The rates of intrauterine death, neonatal death and survival with disability were 3.4%, 5.6% and 7.1%, respectively. The multivariate regression analysis for these poor neonatal outcomes revealed that the significant risk factors included a prolapsed amniotic sac (adjusted odds ratio (aOR), 4.49), preterm labor (aOR, 2.99) and replacement of the prolapsed umbilical cord into the uterus (aOR, 2.87). However, UCP that occurred during labor (aOR, 0.28) and emergency cesarean section (aOR, 0.11) were associated with a reduction in the rates of poor outcomes. The interval between the diagnosis of UCP and delivery was significantly longer in the infants with a poor outcome than intact survival (median 30 versus 24 min, p = 0.048). CONCLUSION: An emergency cesarean section should be carried out immediately to ensure a better outcome for the infant. PMID- 26135793 TI - Risk factors for post-operative wound infection in the setting of chorioamnionitis and cesarean delivery. AB - OBJECTIVE: The objective of this study was to identify factors associated with an increased risk of post-operative wound infection in women with chorioamnionitis who undergo cesarean delivery. METHODS: We conducted a retrospective cohort study of women with clinical chorioamnionitis who underwent cesarean delivery at a tertiary-care center between June 2010 and May 2013. Demographic data, labor and delivery details and post-operative outcomes were collected. Women with and without post-operative wound infections were compared. RESULTS: Of 213 women with clinical chorioamnionitis who underwent cesarean delivery, 32 (15%) developed wound infections. Women with wound infection were more likely to have a body mass index (BMI) greater than or equal to 40 (p = 0.04), chronic hypertension (p = 0.03), leukocytosis on presentation (p = 0.046) or use tobacco (p = 0.002). Women who received ertapenem postpartum were less likely to develop wound infection than those who did not receive antibiotics (p = 0.02) or those that received ampicillin, gentamicin and clindamycin (p = 0.005). CONCLUSIONS: Elevated BMI, tobacco use, chronic hypertension and leukocytosis at admission were associated with an increased risk of wound infection. Ertapenem appeared to reduce the risk of post-operative wound infections in women who had chorioamnionitis and underwent cesarean delivery. This could be considered as a treatment option for this high-risk population. PMID- 26135794 TI - Anti-viral therapy for congenital cytomegalovirus infection: pharmacokinetics, efficacy and side effects. AB - Congenital cytomegalovirus (CMV) infection is the most common congenital infection in the world with approximately 0.5-2% of all live born infants, and can cause early or late severe neurological and neurisensorial damage. Although no drug has been licensed for therapy of congenital CMV infection, ganciclovir (GCV) and its oral pro-drug, valganciclovir (val-GCV), is increasingly being administrated to symptomatic infants, to improve neurodevelopmental and auditory outcome. Other potentially efficacious for therapy of congenital CMV disease are foscarnet and cidofovir, which have only been administered in few cases. A literature search was performed to look for evidence based or scientific articles evaluating pharmacokinetics, efficacy, and side effects of GCV/val-GCVand the other two anti-viral drugs. PMID- 26135795 TI - Have You Ever Seen the Impact of Crossing Fiber in DTI?: Demonstration of the Corticospinal Tract Pathway. AB - OBJECTIVE: The identification of the corticospinal tract (CST) pathway with a deterministic fiber tracking approach is limited because of crossing fibers, especially for the hand fibers of the CST due to the crossing superior longitudinal fasciculus (SLF). We examined a patient with congenital bilateral perisylvian syndrome (CBPS) who did not have the SLF, in order to visualize CST hand fibers that were not affected by crossing fibers. METHODS: A 10-year-old girl without the SLF due to CBPS and three normal healthy subjects participated in this study. We used a deterministic fiber tracking algorithm, and the regions of interest (ROIs) were drawn in the posterior limb of internal capsule (PLIC) and the primary motor cortex. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR) were measured based on the extracted fiber tracts. RESULTS: The ADC values were not different between the normal subjects and the patient with CBPS. The FA, RA, and VR values of the normal subjects were similar, but were relatively higher than those of the patient with CBPS. CONCLUSION: Our results clearly show the impact of the crossing fiber for the hand motor fibers of the CST pathway with deterministic tracking algorithms in diffusion tensor tractography. PMID- 26135796 TI - Exploration of the HIF-1alpha/p300 interface using peptide and Adhiron phage display technologies. AB - The HIF-1alpha/p300 protein-protein interaction plays a key role in tumor metabolism and thus represents a high value target for anticancer drug development. Although several studies have identified inhibitor candidates using rationale design, more detailed understanding of the interaction and binding interface is necessary to inform development of superior inhibitors. In this work, we report a detailed biophysical analysis of the native interaction with both peptide and Adhiron phage display experiments to identify novel binding motifs and binding regions of the surface of p300 to inform future inhibitor design. PMID- 26135797 TI - Purple Glove Syndrome after Phenytoin or Fosphenytoin Administration: Review of Reported Cases and Recommendations for Prevention. AB - The aim of our study was to identify all previously reported cases of phenytoin- or fosphenytoin-associated purple glove syndrome (PGS) and summarize the most current understanding of the pathophysiology, clinical presentation, diagnosis, and treatment of the disease. We searched the English language references from MEDLINE, EMBASE, CINAHL, TOXNET, and gray literature that featured one or more case descriptions of phenytoin- or fosphenytoin-associated PGS after administration and provided information on the clinical setting of the event and associated outcome(s). Descriptive statistics were employed to summarize relevant facts about the cases. We identified 82 unique cases of parenteral phenytoin associated PGS and 5 cases of fosphenytoin-associated PGS that were published from 1984 to 2015. Additionally, we found two cases of PGS associated with oral formulation of phenytoin published from 1999 to 2015. The spectrum of tissue injury ranged from mild local cutaneous reactions around the infusion site to frank limb ischemia. Just over a half of cases reported symptoms after one dose of IV phenytoin. Pathologic findings included evidence for microvascular thrombosis and possible microvascular or subclinical extravasation as a contributing mechanism. Dopper ultrasound and conventional angiography were used in some patients to identify arterial or venous thrombosis. Various treatments were documented including the use of supportive care such as limb elevation and heat or cold application, utilization of systemic antibiotics, anticoagulants, or vasodilators, and local infiltration of hyaluronidase, heparin, or other compounds. In a small number of patients, invasive interventions such as regional anesthesia, thrombectomy, fasciotomy, and debridement were described. Time to resolution varied from days to weeks. Resolution of PGS without deficits was documented in the majority of cases. Skin changes followed by sensory and motor deficits were described in 16, 6, and 5 cases, respectively. Four patients underwent skin grafting and eight patients required limb amputation. Death as a result of PGS was documented in two patients. PGS associated with oral and injectable phenytoin or parenteral fosphenytoin has been documented in the literature and sometimes includes significant vascular thrombosis and potentially limb-threatening ischemia. Avoidance of small hand veins, adherence to recommended IV administration guidelines and monitoring of the infusion site for reactions should be considered to decrease the morbidity of IV phenytoin or fosphenytoin use. Patients with PGS and evidence of decreased distal perfusion should undergo prompt vascular imaging and potential intervention to avoid ischemic sequelae. Alternative anticonvulsant drugs should be considered in patients at risk for PGS when possible. PMID- 26135798 TI - Direct Observation of Degenerate Two-Photon Absorption and Its Saturation in WS2 and MoS2 Monolayer and Few-Layer Films. AB - The optical nonlinearity of WS2 and MoS2 monolayer and few-layer films was investigated using the Z-scan technique with femtosecond pulses from the visible to the near-infrared range. The nonlinear absorption of few- and multilayer WS2 and MoS2 films and their dependences on excitation wavelength were studied. WS2 films with 1-3 layers exhibited a giant two-photon absorption (TPA) coefficient as high as (1.0 +/- 0.8) * 10(4) cm/GW. TPA saturation was observed for the WS2 film with 1-3 layers and for the MoS2 film with 25-27 layers. The giant nonlinearity of WS2 and MoS2 films is attributed to a two-dimensional confinement, a giant exciton effect, and the band edge resonance of TPA. PMID- 26135799 TI - Respiration and metabolism of the resting European paper wasp (Polistes dominulus). AB - The European paper wasp, Polistes dominulus Christ, is an abundant wasp species in South and Central Europe which dispersed to the north in recent times. Polistes dominulus exhibits an energy-extensive mode of life, spending much time resting at the nest, which should be reflected in adaptations regarding gas exchange and standard metabolism. We analysed the resting metabolism (CO2 emission) of Polistes dominulus workers in the ambient temperature range an individual may be exposed to during a breeding season (T a = 2.4-40.6 degrees C) via flow through respirometry. Behaviour and endothermic activity were assessed by infrared thermography. With rising T a, CO2 release followed an exponential increase from 27 to 149 and 802 nl g(-1) min(-1) at T a = 3, 20 and 35 degrees C, respectively. Measurements of the thermal regime at the nest showed that resting P. dominulus are most of the time in the lower range of their standard metabolic curve. A comparison with a "highly energetic" wasp like Vespula sp. revealed that Polistes dominulus not only optimises behaviour but also reduces metabolism to save energy. The CO2 emission patterns changed with ambient temperature, from discontinuous (<= 25 degrees C) to cyclic (25-36 degrees C) and continuous gas exchange at higher temperatures. A pronounced break appeared in the data progression regarding cycle frequency and CO2 emission per gas exchange cycle between 15 and 10 degrees C. This striking change in gas exchange features indicates a physiological adaptation to special respiratory requirements at low temperatures. PMID- 26135800 TI - In vitro differentiation of porcine aortic vascular precursor cells to endothelial and vascular smooth muscle cells. AB - Recent findings suggest that progenitor and multipotent mesenchymal stromal cells (MSCs) are associated with vascular niches. Cells displaying mesenchymal properties and differentiating to whole components of a functional blood vessel, including endothelial and smooth muscle cells, can be defined as vascular stem cells (VSCs). Recently, we isolated a population of porcine aortic vascular precursor cells (pAVPCs), which have MSC- and pericyte-like properties. The aim of the present work was to investigate whether pAVPCs possess VSC-like properties and assess their differentiation potential toward endothelial and smooth muscle lineages. pAVPCs, maintained in a specific pericyte growth medium, were cultured in high-glucose DMEM + 10% FBS (long-term medium, LTM) or in human endothelial serum-free medium + 5% FBS and 50 ng/ml of hVEGF (endothelial differentiation medium, EDM). After 21 days of culture in LTM, pAVPCs showed an elongated fibroblast-like morphology, and they seem to organize in cord-like structures. qPCR analysis of smooth muscle markers [alpha-smooth muscle actin (alpha-SMA), calponin, and smooth muscle myosin (SMM) heavy chain] showed a significant increment of the transcripts, and immunofluorescence analysis confirmed the presence of alpha-SMA and SMM proteins. After 21 days of culture in EDM, pAVPCs displayed an endothelial cell-like morphology and revealed the upregulation of the expression of endothelial markers (CD31, vascular endothelial-cadherin, von Willebrand factor, and endothelial nitric oxide synthase) showing the CD31 typical pattern. In conclusion, pAVPCs could be defined as a VSC-like population considering that, if they are maintained in a specific pericyte medium, they express MSC markers, and they have, in addition to the classical mesenchymal trilineage differentiation potential, the capacity to differentiate in vitro toward the smooth muscle and the endothelial cell phenotypes. PMID- 26135801 TI - Atrophy, inducible satellite cell activation, and possible denervation of supraspinatus muscle in injured human rotator-cuff muscle. AB - The high frequency of poor outcome and chronic pain after surgical repair of shoulder rotator-cuff injury (RCI) prompted this study to explore the potential to amplify muscle regeneration using nitric oxide (NO)-based treatment. After preoperative magnetic resonance imaging (MRI), biopsies of supraspinatus and ipsilateral deltoid (as a control) were collected during reparative surgery for RCI. Muscle fiber diameter, the pattern of neuromuscular junctions observed with alpha-bungarotoxin staining, and the gamma:epsilon subunit ratio of acetylcholine receptors in Western blots were examined in tandem with experiments to determine the in vitro responsiveness of muscle satellite cells to activation (indicated by uptake of bromodeoxyuridine, BrdU) by the NO-donor drug, isosorbide dinitrate (ISDN). Consistent with MRI findings of supraspinatus atrophy (reduced occupation ratio and tangent sign), fiber diameter was lower in supraspinatus than in deltoid. ISDN induced a significant increase over baseline (up to 1.8-fold), in the proportion of BrdU+ (activated) Pax7+ satellite cells in supraspinatus, but not in deltoid, after 40 h in culture. The novel application of denervation indices revealed a trend for supraspinatus muscle to have a higher gamma:epsilon subunit ratio than deltoid (P = 0.13); this ratio inversely with both occupancy ratio (P < 0.05) and the proportion of clusters at neuromuscular junctions (P = 0.05). Results implicate possible supraspinatus denervation in RCI and suggest NO donor treatment has potential to promote growth in atrophic supraspinatus muscle after RCI and improve functional outcome. PMID- 26135802 TI - Motor patterns of the small intestine explained by phase-amplitude coupling of two pacemaker activities: the critical importance of propagation velocity. AB - Phase-amplitude coupling of two pacemaker activities of the small intestine, the omnipresent slow wave activity generated by interstitial cells of Cajal of the myenteric plexus (ICC-MP) and the stimulus-dependent rhythmic transient depolarizations generated by ICC of the deep muscular plexus (ICC-DMP), was recently hypothesized to underlie the orchestration of the segmentation motor pattern. The aim of the present study was to increase our understanding of phase amplitude coupling through modeling. In particular the importance of propagation velocity of the ICC-DMP component was investigated. The outcome of the modeling was compared with motor patterns recorded from the rat or mouse intestine from which propagation velocities within the different patterns were measured. The results show that the classical segmentation motor pattern occurs when the ICC DMP component has a low propagation velocity (<0.05 cm/s). When the ICC-DMP component has a propagation velocity in the same order of magnitude as that of the slow wave activity (~1 cm/s), cluster type propulsive activity occurs which is in fact the dominant propulsive activity of the intestine. Hence, the only difference between the generation of propagating cluster contractions and the Cannon-type segmentation motor pattern is the propagation velocity of the low frequency component, the rhythmic transient depolarizations originating from the ICC-DMP. Importantly, the proposed mechanism explains why both motor patterns have distinct rhythmic waxing and waning of the amplitude of contractions. The hypothesis is brought forward that the velocity is modulated by neural regulation of gap junction conductance within the ICC-DMP network. PMID- 26135804 TI - Cochrane corner: vitamin K for improved anticoagulation control in patients receiving warfarin. PMID- 26135803 TI - Riociguat for pulmonary arterial hypertension associated with congenital heart disease. AB - OBJECTIVE: The Pulmonary Arterial hyperTENsion sGC-stimulator Trial-1 (PATENT-1) was a randomised, double-blind, placebo-controlled phase III trial evaluating riociguat in patients with pulmonary arterial hypertension (PAH). PATENT-2 was an open-label long-term extension to PATENT-1. Here, we explore the efficacy and safety of riociguat in the subgroup of patients with persistent/recurrent PAH after correction of congenital heart disease (PAH-CHD) from the PATENT studies. METHODS: In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo for 12 weeks; efficacy assessments included change from baseline to study end in 6-min walking distance (6MWD; primary), pulmonary vascular resistance (PVR), N-terminal of the prohormone of brain natriuretic peptide (NT-proBNP), WHO functional class (WHO FC) and time to clinical worsening. In PATENT-2, eligible patients from PATENT-1 received long-term riociguat (maximum 2.5 mg three times daily); the primary assessment was safety and tolerability. All PAH-CHD patients had a corrected cardiac defect. RESULTS: In PATENT-1, riociguat increased mean+/-SD 6MWD from baseline to week 12 by 39+/ 60 m in patients with PAH-CHD versus 0+/-42 m for placebo. Riociguat also improved several secondary variables versus placebo, including PVR (-250+/-410 vs -66+/-632 dyn.s/cm(5)), NT-proBNP (-164+/-317 vs -46+/-697 pg/mL) and WHO FC (21%/79%/0% vs 8%/83%/8% improved/stabilised/worsened). One patient experienced clinical worsening (riociguat 1.5 mg group). Riociguat was well tolerated. In PATENT-2, riociguat showed sustained efficacy and tolerability in patients with PAH-CHD at 2 years. CONCLUSIONS: Riociguat was well tolerated in patients with PAH-CHD and improved clinical outcomes including 6MWD, PVR, WHO FC and NT-proBNP. TRIAL REGISTRATION NUMBER: The clinical trials numbers are NCT00810693 for PATENT 1 and NCT00863681 for PATENT-2. PMID- 26135805 TI - Photoelectron Spectroscopy and Ionic Fragmentation of OSeCl2 and Its Analogue OSCl2 under VUV Irradiation. AB - The electronic structure and the dissociative ionization of selenium oxychloride, OSeCl2, have been investigated in the valence region by using results from both photoelectron spectroscopy (PES) and synchrotron-based photoelectron photoion coincidence (PEPICO) spectra. The PES is assigned with the help of quantum chemical calculations at the outer-valence Green's function (OVGF) and symmetry adapted cluster/configuration interaction (SAC-CI) levels. The first energy ionization is observed at 11.47 eV assigned to the ionization of electrons formally delocalized over the Se, Cl, and O lone pair orbitals. Irradiation of OSeCl2 with photons in the valence region leads to the formation of OSeCl2(*+), OSeCl(+), SeCl2(*+), SeCl(+), and SeO(*+) ions. Furthermore, the inner shell Se 3p, Cl 2p, and Se 3s electronic regions of OSeCl2 together with S 2p, Cl 2p, and S 2s electronic regions of thionyl chloride, OSCl2, have been studied by using tunable synchrotron radiation. Thus, total ion yield spectra and the fragmentation patterns deduced from PEPICO spectra at the various excitation energies have been studied. Cl(+), O(*+), and Se(*+) ions appear as the most intense fragments in the OSeCl2 PEPICO spectra, like in the sulfur analogue OSCl2, whose photofragmentation is dominated by the Cl(+), O(*+), and S(*+) ions. Fragmentation processes in OSCl2 leading to the formation of the double coincidences involving atomic ions appear as the most intense in the PEPIPICO spectra. PMID- 26135806 TI - Orthostatic hypotension and associated conditions in geriatric inpatients. AB - Screening of orthostatic hypotension (OH) was performed in 285 patients aged 75 years. Current drugs, reasons for admission, geriatric syndromes, and confounding medical conditions were collected. Patients with OH (n = 116, 41%) as compared to those without OH (n = 169) more frequently (P < 0.01) presented falls in the last 6 months (62 vs. 40%, P < 0.001), a fall as the reason for the current admission (49 vs. 26%, P < 0.001), feeling of fainting (20 vs. 6%, P = 0.002), syncope (29 vs. 4%, P < 0.001) or functional decline (71 vs. 47%, P = 0.012). No difference was observed between the two groups in terms of age (85 +/- 5 vs. 84 +/- 4 years), gender (59 vs. 50% female), common geriatric conditions (e.g. malnutrition 46 vs. 58%, dementia 22 vs. 26%), comorbidity or confounding conditions (dehydration 28 vs. 30%, sepsis 2 vs. 6%). No difference was detected in the use of drugs with psychotropic cardiovascular or diuretic effect, or in their associations. Orthostatic hypotension is frequent upon hospital admission and should be screened, particularly in geriatric fallers. This absence of relation between OH and drugs use suggests that non-pharmacological interventions should be first attempted in older inpatients with OH before deciding to reduce or withdraw useful drugs. PMID- 26135807 TI - Inhibitory effects of valproic acid in DNA double-strand break repair after irradiation in esophageal squamous carcinoma cells. AB - Radiation therapy is one of the most promising therapeutic strategies in unresectable esophageal squamous cell carcinoma (ESCC). The histone deacetylase (HDAC) inhibitor has been shown to enhance radiosensitivity. Valproic acid (VPA) is a well-known drug used to treat seizure disorders and epilepsy, and has been shown to inhibit HDACs. We recently reported that a clinically safe dose of VPA enhances radiation-induced cytotoxicity in human ESCC cells. However, the mechanism of radiosensitizing effect of VPA has not yet been confirmed. The present study examined the effect of VPA on DNA double-strand break (DSB) repair after radiation in the human ESCC cell lines KES, TE9 and TE11 by examining H2AX phosphorylation (gammaH2AX) levels as a marker of radiation-induced DSBs. The present study also examined whether VPA inhibited radiation-induced DNA DSB repair by suppressing non-homologous end joining (NHEJ), focusing particularly on the acetylation of Ku70. VPA was shown to prolong gammaH2AX levels after irradiation in all three ESCC cell lines. Moreover, prolonged gammaH2AX foci formation after irradiation was also observed by immunocytochemistry following VPA pretreatment in KES and TE9 cells. VPA was shown to induce Ku70 acetylation after irradiation in all three ESCC cell lines. Our results suggest that VPA prolonged radiation-induced DSBs by inhibiting NHEJ in DSB repair pathways in ESCC. VPA could therefore be used as an effective radiosensitizer in ESCC radiotherapy. PMID- 26135808 TI - Substituent and Charge Transfer Effects on Memory Behavior of the Ambipolar Poly(triphenylamine)s. AB - A series of poly(triphneylamine)s (CN-PTPA, 2CN-PTPA, 3CN-PTPA, and NO2-PTPA) with pendent acceptors (cyano, dicyanovinyl, tricyanovinyl, and nitro) have been readily synthesized by oxidative coupling polymerization using FeCl3 as oxidant. The tunable memory properties of the ITO/polymer/Al sandwiched memory devices including DRAM, SRAM, and WORM could be achieved by introducing substituent acceptors with different extent of electronic delocalization and electron withdrawing intensity into the poly(triphenylamine)s. The highly fluorescent CN PTPA exhibited volatile DRAM memory characteristic due to the large band gap and weak intramolecular charge transfer capability. 2CN-PTPA and 3CN-PTPA showed volatile SRAM memory property with retention time of 5 and 14 min, respectively, depending on electron-withdrawing capability of the acceptors. Furthermore, NO2 PTPA afforded nonvolatile WORM memory behavior attributed to the charge could be trapped into the nonconjugated nitro group even though the dipole moment and electron-withdrawing capability of nitro group were weaker than cyanovinyl groups. Moreover, except NO2-PTPA, all the devices derived from cyano-containing ambipolar polymers including CN-PTPA, 2CN-PTPA, and 3CN-PTPA could be switched to the ON state and exhibited WORM memory behavior in positive unipolar I-V switching. This phenomenon indicated that the Al atoms preferentially interact with poly(triphneylamine)s containing cyano than nitro substituents. PMID- 26135809 TI - Rethinking fast and slow based on a critique of reaction-time reverse inference. AB - Do people intuitively favour certain actions over others? In some dual-process research, reaction-time (RT) data have been used to infer that certain choices are intuitive. However, the use of behavioural or biological measures to infer mental function, popularly known as 'reverse inference', is problematic because it does not take into account other sources of variability in the data, such as discriminability of the choice options. Here we use two example data sets obtained from value-based choice experiments to demonstrate that, after controlling for discriminability (that is, strength-of-preference), there is no evidence that one type of choice is systematically faster than the other. Moreover, using specific variations of a prominent value-based choice experiment, we are able to predictably replicate, eliminate or reverse previously reported correlations between RT and selfishness. Thus, our findings shed crucial light on the use of RT in inferring mental processes and strongly caution against using RT differences as evidence favouring dual-process accounts. PMID- 26135810 TI - HIV burden in men who have sex with men: a prospective cohort study 2007-2012. AB - We conducted a prospective cohort study among HIV-negative MSM aged 18 years or older between 2007 and 2012 in Beijing, China to measure the rates of incident HIV and identify risk factors for infection. Among 5,800 participants evaluated at enrollment, we identified 486 prevalent cases of HIV (8.4%). Among the 3,625 enrollees who were HIV-negative at enrollment and completed at least one follow up interview, we identified 440 incident cases of HIV in the follow up period: this constituted an HIV incidence rate of 7.1 per 100 person-years (95% CI: 6.4 7.7). Early treatment of syphilis may have significantly reduced risk of HIV infection (RR: 1.45, 95% CI: 1.11-1.93), while MSM presenting perfect compliance in the cohort did not show reduction in HIV infection. Our study suggested that HIV incidence has been remained high in this sample of Chinese MSM during the intensive preventive intervention, suggesting that we need to find new strategies to prevent HIV infection in this population. PMID- 26135811 TI - The Cumulated Stone Diameter: A Limited Tool for Stone Burden Estimation. AB - OBJECTIVE: To compare the performance of the main methods used to estimate stone burden in order to improve and standardize preoperative evaluation of stone disease. METHODS: From January 2012 to June 2013, a series of consecutive retrograde intrarenal stone surgery was prospectively evaluated at a single institute. All patients had a pre- and postoperative CT scan. The stone burden was estimated using 3 methods: the cumulative stone diameter (M1), Ackermann's formula (M2), and the sphere formula (M3). The predictive value of the postoperative stone-free status of these methods was then compared. RESULTS: Overall (n = 142), the stone-free rate was 64%. The three methods (M1, M2, and M3) were all predictive of stone-free status for stones <20 mm (P = .0076, .018, and .016, respectively). However, only M2 and M3 were significant for stones >20 mm (P = .0024 and .023). Using receiver operating characteristic curves, we found that areas under the curve were 0.73, 0.70, and 0.71 for stones below 20 mm and 0.53, 0.74, and 0.74 for stones above 20 mm for M1, M2, and M3, respectively. In multivariate analysis, M1 and M3 were both found to be independently associated with the stone-free status in the whole series (P <.001 and .011, respectively). However, for stones above 20 mm, only M3 was significant (P = .020). CONCLUSION: Evaluation of the stone burden is an important predictor of the outcome of retrograde intrarenal stone surgery. For stones below 20 mm, all the three methods approximate stone burden correctly; however, for the stones above 20 mm, calculation of volume is recommended. PMID- 26135812 TI - Artificial Urinary Sphincter Outcomes in the "Fragile Urethra". AB - OBJECTIVE: To assess artificial urinary sphincter (AUS) outcomes in challenging post-prostatectomy patients with a "fragile urethra" at risk for urethral erosion. METHODS: An institutional retrospective review of all AUS placements between August 2004 and March 2014 was performed. A "fragile urethra" was defined as a history of pelvic radiation, previous failed AUS, previous urethroplasty, or cystoscopic and/or clinical findings of urethral atrophy. The primary outcome was continence, defined as requiring <=1 pad per day. Secondary outcomes included 90 day complications, need for further treatment, change in continence pads, and patient-reported satisfaction. RESULTS: Thirty patients were identified as having a "fragile urethra." Thirteen of these patients underwent a transcorporal AUS (TCAUS) and 17 had a standard AUS cuff placement. Seventeen patients had radiation, 8 had a previous eroded AUS, and 10 had a prior urethroplasty. Five patients had multiple risk factors for urethral erosion. Continence was achieved in 77% (23/30), 97% (29/30) were improved, and the mean change in pads was 6.0 +/ 2.8. Only 7% (2/30) required explantation, both for erosion. When the TCAUS and standard AUS groups were compared, no differences were noted in continence rates (P = .43), improvement (P = 1.00), explantation rates (P = .18), or erosion rates (P = .18), despite TCAUS having a higher proportion of previous urethroplasties. CONCLUSION: AUS is a viable treatment option for post-prostatectomy incontinence, even in the fragile urethra. TCAUS may be utilized in patients with a very high risk for atrophy with similar continence and complication rates compared with standard AUS. PMID- 26135813 TI - Combined Vaginal Pelvic Floor Electrical Stimulation (PFS) and Local Vaginal Estrogen for Treatment of Overactive Bladder (OAB) in Perimenopausal Females. Randomized Controlled Trial (RCT). AB - OBJECTIVE: To evaluate the efficacy of combined vaginal pelvic floor electrical stimulation (PFS) and local vaginal estrogen in treatment of female overactive bladder (OAB). MATERIAL AND METHODS: This is a randomized controlled trial carried out on 315 perimenopausal females with OAB who were randomly allocated into 3 equal groups. Group A underwent PFS using vaginal probes twice weekly for 12 sessions. Group B received local vaginal estrogen, whereas group C received both PFS and local estrogen. All patients were evaluated by a voiding diary, quality-of-life questionnaire, vaginal examination, urine analysis, blood sugar, ultrasonography, and urodynamic study before and after therapy. Patients were followed up 1 week, 3, and 6 months post-therapy. The analyzed variables included day and night time frequency, incontinence episodes, urgency, quality of life, detrusor overactivity), and functional bladder capacity). Outcome measure was urge incontinence. RESULTS: Within each group, there was a statistically significant improvement in all variables after treatment. Improvement of urgency was better in group C than in groups A and B (P = .000, .009). Improvement of incontinence was better in groups A and C than in group B (P = .005, .004). Follow-up showed worsening of symptoms within 6 months in all groups except incontinence in group C. CONCLUSION: Vaginal PFS and estrogen found to be effective in treating OAB symptoms in perimenopausal females. Estrogen seems to augment the effect of PFS especially in the treatment of urgency incontinence and can delay its recurrence. PMID- 26135814 TI - Reduced Postvasectomy Semen Analysis Testing With the Implementation of Special Clearance Parameters. AB - OBJECTIVE: To determine the applicability of postvasectomy special clearance parameters (<100,000 nonmotile sperm/mL on semen analysis) suggested by the American Urological Association and to define the associated cost savings with avoidance of further testing. MATERIALS AND METHODS: We retrospectively reviewed the cohort of men undergoing vasectomy from December 2009 to August 2012 at a single institution. Patient demographics and postvasectomy semen analysis (PVSA) results were collected for clearance parameter comparisons. RESULTS: During the study period, 230 patients underwent vasectomy with a mean +/- SD age of 36.4 +/- 6.5 years. Among the cohort, 83.5% were married and 95.2% had one or more children. The initial PVSA was completed by 111 (48.3%) patients at a mean of 17.8 weeks (range 4-45) following vasectomy. Sperm was identified on initial PVSA in 40 patients (36.0%); 1 patient was found to have motile sperm. Of 39 patients, 38 (97.4%) with nonmotile sperm on PVSA could be cleared to cease other contraceptives based on the most recent clearance guidelines. For those completing an initial PVSA, postvasectomy clearance increased from 64.0% to 98.2% representing a potential cost savings of $2356 in repeat semen testing. CONCLUSION: Postvasectomy contraceptive clearance can be greatly increased when rare nonmotile sperm parameters are included although postvasectomy semen testing compliance remains poor. PMID- 26135815 TI - Long-term Outcomes Following Artificial Urinary Sphincter Placement: An Analysis of 1082 Cases at Mayo Clinic. AB - OBJECTIVE: To evaluate long-term device outcomes following primary artificial urinary sphincter (AUS) implantation. MATERIALS AND METHODS: We identified 1802 male patients with stress urinary incontinence that underwent AUS placement from 1983 to 2011. Of these, 1082 (60%) were involving primary implantations and comprise the study cohort. Multiple clinical and surgical variables were evaluated for potential association with treatment failure, defined as any secondary surgery. Patient follow-up was obtained through office examination, operative report, and written or telephone correspondence. RESULTS: Patients undergoing AUS implantation had a median age of 71 years (interquartile range 66 76) and median follow-up of 4.1 years (interquartile range 0.8-7.7). Overall, 338 of 1082 patients (31.2%) underwent secondary surgery, including 89 for device infection and/or erosion, 131 for device malfunction, 89 for urethral atrophy, and 29 for pump malposition or tubing complications. No patient-related risk factors were independently associated with an increased risk of secondary surgery on multivariable analysis. Secondary surgery-free survival was 90% at 1 year, 74% at 5 years, 57% at 10 years, and 41% at 15 years. CONCLUSION: Primary AUS implantation is associated with acceptable long-term outcomes. Recognition of long-term success is important for preoperative patient counseling. PMID- 26135817 TI - Context for Practice: Persistent Challenges of Pressure Ulcer Prevention. PMID- 26135818 TI - Peer-to-Peer Education: The PEP Talk: Diabetes, Healthy Feet and You Program in Canada. PMID- 26135816 TI - Executive function and suicidality: A systematic qualitative review. AB - Deficits in executive function (EF) have been proposed as a possible explanation for the "cognitive rigidity" often observed in suicidal individuals. This article provides a systematic review of the existing literature testing the relations between EF and suicidality, across various diagnostic and demographic populations, using the influential multidimensional model of EF proposed by Miyake and colleagues (2000) as an organizing framework. Forty-three journal articles on this topic published before January of 2014 were reviewed. Collectively, results from these studies provide tentative support for an association between EF deficits and suicidality. However, there is some evidence that this association is moderated by other factors (e.g., suicide attempt lethality). Importantly, this relationship may vary across diagnostic groups. Specifically, more studies that used depressive disorder samples reported some positive findings (75%), followed by mixed diagnostic samples (54%). In contrast, fewer positive findings have emerged from studies with bipolar or psychotic disorder samples (29% and 33% respectively), and some even found that suicidality is associated with better EF in individuals with psychotic disorders. Firm conclusions about relationships between specific dimensions of EF and/or aspects of suicidality are difficult to draw this time. Limitations of the existing literature and corresponding directions for future research are discussed. PMID- 26135819 TI - Analysis of the Pressure Distribution Qualities of a Silicone Border Foam Dressing. AB - PURPOSE: To determine whether application of a silicone foam dressing is associated with decreased interface pressures when applied to the heel. DESIGN: Prospective, within-subjects design. SUBJECTS AND SETTING: The study was conducted in a community-based hospital using a convenience sample of 50 healthy volunteers with a mean age of 39.6 years and mean body mass index of 26.6; 70% were female. METHODS: Application of the silicone border foam dressing was randomized between the left and right heels. Participants were asked to lie down in the supine position on a viscoelastic foam mattress. Interface pressure measurements were captured using a pressure mapping system; measurements were taken once with the dressing applied to the heel (intervention map) and once without (control map). Data were captured after a 4-minute time period allowing stabilization. Analysis was based on mean interface pressure; data points were collected for both heels in each of the 2 frames, yielding 4 observations per subject. RESULTS: Application of the dressing was associated with a significant decrease in average pressure measurements as compared to the heel with no dressing applied (P < .001). Application of the dressing did not impact pressure readings for the heel to which no dressing was applied (P = .53), and application of the dressing to either the left or right heel did not impact pressure readings (ie, the random effect was insignificant; P = .9). CONCLUSIONS: Application of a silicone border foam dressing is associated with significant reduction in interface pressure and may be considered as part of a pressure ulcer prevention program. PMID- 26135820 TI - Health-Related Quality of Life in Elderly Patients With Pressure Ulcers in Different Care Settings. AB - PURPOSE: The purpose of this study was to measure and compare health-related quality of life in elderly patients with pressure ulcers in different health care settings (home care acute care facility, and long-term care facility [LTCF]). DESIGN: Cross-sectional comparative study. SUBJECTS AND SETTING: One hundred ten elderly patients with (n = 36) and without (n = 74) pressure ulcers living in LTCFs, hospitals, or at home. The research setting included 1 tertiary and 2 community-based hospitals, 10 LTCFs, and 18 community health centers in Brazil. METHODS: The Mini-Mental State Examination, Braden Scale for Predicting Pressure Sore Risk, and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were used to assess cognitive status, pressure ulcer risk, and health-related quality of life, respectively. RESULTS: Compared with those without pressure ulcers, elderly patients with pressure ulcers reported significantly lower (worse) SF-36 scores on physical functioning (P < .001) and role physical (P < .05) in all settings, and on social functioning (P = .045) and role emotional (P = .036) in LTCFs. Subjects in hospitals with pressure ulcers scored significantly higher (better) SF-36 scores on mental health (P = .046) and vitality (P = .009). Hospitalized patients without pressure ulcers had lower SF-36 scores on bodily pain (P = .007) and general health (P = .026) than those living in LTCFs or at home. Patients without pressure ulcers in LTCFs had significantly lower Mini Mental State Examination scores (lower cognitive status) than those living in other settings (P = .001). CONCLUSIONS: Elderly patients with pressure ulcers who were hospitalized and living at home or in LTCFs reported low scores on physical functioning and role physical, and LTCF residents also reported low scores on social functioning and role emotional. This shows the need for an environment that includes health care professionals prepared to implement strategies for pressure ulcer prevention. PMID- 26135821 TI - Uncertainty and Adaptation Among Adults Living With Incontinent Ostomies. AB - PURPOSE: The purpose of this study was to examine the relationship between uncertainty and adaptation among individuals requiring surgery resulting in an incontinent ostomy. DESIGN: Descriptive correlational study. SUBJECTS AND SETTING: The study sample comprised adult persons with incontinent ostomies created during calendar years 2009 and 2010. The research setting was an academic medical in the Northeastern United States. Respondents were 18 to 83 years old, with a mean age of 53.88 +/- 19.58 years (mean +/- SD); 54.9% were women. METHODS: A WOC nurse reviewed electronic medical records of patients who had undergone incontinent ostomy surgery to determine whether they met inclusion criteria. A letter outlining the study was mailed to potential subjects requesting their participation; 2 validated instruments were included: the Ostomy Adjustment Scale and the Mishel Uncertainty in Illness Scale-Adult Form. The form also queried demographic information. After 2 weeks, a postcard was sent to remind study participants to complete and return the documents. RESULTS: The leading medical diagnosis resulting in ostomy surgery was cancer (45.1%), followed by Crohn's disease or ulcerative colitis (35.3%). The sample was evenly distributed between those having their ostomies less than 1 year and those having them more than 1 year. Most incontinent stomas were ileostomies (60.8%), 33.3% were colostomies, and 5.9% were urostomies. Nearly three-quarters (74.5%) indicated that they were independent regarding ostomy self-care. CONCLUSION: The results suggest a strong association between certainty and adaptation among adult patients with an incontinent ostomy. The WOC nurse, as patient advocate, can offer persons with a new ostomy an overall perspective on the ostomy experience. PMID- 26135822 TI - Is the Use of a Support Bridge Beneficial for Preventing Stomal Retraction After Loop Ileostomy? A Prospective Nonrandomized Study. AB - PURPOSE: A temporary defunctioning loop ileostomy is frequently created during low colorectal or coloanal anastomosis to prevent peritoneal sepsis associated with anastomotic leakage. We investigated whether routine support bridge placement prevents stoma retraction after the formation of a loop ileostomy. DESIGN: Prospective, nonrandomized trial. SUBJECTS AND SETTING: The study sample comprised 32 consecutive patients who underwent defunctioning loop ileostomy at an academic tertiary care center in Seoul Korea from February to September 2010. METHODS: Patients were nonrandomly allocated to "no bridge," "short-term bridge" (1 week), and "long-term bridge" (3 weeks) groups based on the surgeon's clinical judgment. Group differences in stoma height changes over time were analyzed. RESULTS: Subjects' mean age was 59.5 (range: 43-82) years, and the male-to-female ratio was 2.2:1.0. The mean heights of the stoma on postoperative day 2 and postoperative month 3, respectively, were 1.07 +/- 0.16 cm (mean +/- SD) and 0.81 +/- 0.17 cm in the no-bridge group, 1.70 +/- 0.29 cm and 1.21 +/- 0.18 cm in the short-term bridge group, and 1.18 +/- 0.16 cm and 1.01 +/- 0.20 cm in the long term bridge group. The changes in the stoma height 3 months after the surgery showed no statistically significant differences among the groups (P = .430). Stoma Quality of Life scores at 3 weeks (47.4 vs 46.1; P = .730) were similar for patients with and without bridges. However, a significantly greater number of patients with bridges reported difficulty with pouch changes compared to those without bridges (72.7% vs 14.3%; P = .002). CONCLUSIONS: Routine use of support bridges during loop ileostomy is unnecessary and inconvenient to patients. If a support bridge must be used, it can be removed early. PMID- 26135823 TI - Health-Related Quality of Life in Community-Dwelling Persons With Ostomies: The Physical Functioning Domain. AB - PURPOSE: The purpose of this study was to explore health-related quality of life in persons living with ostomies and to compare these findings with a community dwelling population residing in the United States. This detailed analysis reports the magnitude of physical limitations for each domain within the Physical Component Summary. DESIGN: Cross-sectional design. SUBJECTS AND SETTING: Potential respondents were identified by randomly sampling from proprietary databases containing e-mail contact information provided by persons living with a fecal or urinary ostomy. The sample comprised 2329 persons with ostomies; most were male (53.4%), and living with a single fecal ostomy (82.7%) or urostomy (21%). Health-related quality of life was measured using the Medical Outcomes Study Short Form-36 version 2. RESULTS: Persons with an ostomy are more likely to experience limitations in vigorous activity than individuals in the general population (odds ratio [OR]: 3.46, 95% confidence interval [CI]: 3.03-3.96) and activities requiring moderate exertion (OR: 2.72, 95% CI: 2.45-3.03). The prevalence of respondents reporting limitations was highest for those with colostomies. CONCLUSIONS: Persons with ostomies are more likely to report significant limitations in physical health than age-matched persons in the general population. Additional research is needed to determine whether these limitations are caused by the ostomy itself or a combination of factors including the underlying disease that led to creation of a stoma. PMID- 26135824 TI - Is it Feasible to Use Incontinence-Associated Dermatitis Assessment Tools in Routine Clinical Practice in the Long-term Care Setting? AB - PURPOSE: To investigate the feasibility of using incontinence-associated dermatitis (IAD) tools in routine clinical practice by asking nursing home staff (RNs and non-RN caregivers) and tissue viability specialty (TVS) nurses to evaluate 3 instruments and a 4-point severity scoring system for describing and grading IAD examples captured in photographs of skin underneath absorptive pads in nursing home patients. DESIGN: Feasibility study. SUBJECTS AND SETTING: Twelve female nursing home residents whose incontinence was managed with pads and who had previously been identified as experiencing IAD were recruited, along with 16 nursing home staff (6 RNs and 10 non-RNs) and 10 TVS nurses. METHODS: Weekly high quality photographs were taken of the skin beneath absorptive pads of nursing home residents for 8 weeks yielding a library of 78 photographs. A subset of 10 representative photographs was chosen. The 16 nursing home staff and 10 TVS nurses were then asked to describe and grade the IAD in the 10 photographs using 3 IAD instruments and simple severity scoring system (SSS) developed for this study. Particular attention was paid to identifying any practical challenges staff encountered in conducting their task. RESULTS: The TVS nurses were able to use all 3 IAD instruments and the SSS and reported that they could incorporate them into their clinical practice with relative ease. Although the RNs were able to use the 3 instruments adequately with some initial assistance, they generally felt that they were too busy to complete them. By contrast, they reported that they found the SSS simple and quick enough to incorporate into their routine practice. The caregivers had difficulty with the text-based instruments, especially if English was not their first language, and they were only able to use the SSS. The caregivers' SSS scores for a given photograph varied more than TVS nurse scores, but the correlation between the mean TVS scores, which were operationally defined as the gold standard for purposes of this study, and the mean RN and caregiver scores (R = 0.811) were fairly high. CONCLUSIONS: Existing IAD instruments are too time-consuming and linguistically complex for use in routine clinical practice in nursing homes. We found that staff generally found the SSS easy to judge IAD severity based on pictures used in the study. This finding suggests that the SSS could be improved by adding reference photographs of skin illustrating each of the 4 points on the scale. Such an instrument could be designed and validated with an emphasis on integration into current clinical practice pathways. PMID- 26135825 TI - Implementation of a Bowel Management Program in Critical Care. AB - PURPOSE: The purpose of this study was to examine the effectiveness of a unit based, educational program on implementation of a sustainable bowel management program in a critical care setting. SUBJECTS AND SETTING: Two hundred thirty nurses in 6 critical care units within a 750-bed level I trauma hospital and 400 bed university academic teaching hospital participated in the study. METHODS: Data collection and analysis were guided by a quasi-experimental pre-/postdesign. An evidence-based, interactive Web-based education program was developed. The education program consisted of 3 components: (1) knowledge acquisition (Web-based education module), (2) skill acquisition (unit-based skill session performance and competency), and (3) mastery experiences (self-efficacy). Data collected included pre- and posteducation module test scores, skill-acquisition competency, and self-efficacy scores. RESULTS: The Web-based education module pre- and posttest scores for 225 participants showed significant (P < .001) improvement in knowledge scores. All participants (100%) completed the skill acquisition sessions successfully during the unit-based performance session. Nurses' self efficacy scores significantly improved (P < .001) over the course of this study period. Eighty-six percent (n = 125) of critical care nurses reported enhanced collaboration with the WOC nurses and clinical nurse specialists. CONCLUSION: Study findings support the use of a structured, evidence-based educational program incorporating a multimethod approach to implement practice change for critical care. PMID- 26135826 TI - Fecal Incontinence and Quality of Life in Adults With Rectal Cancer After Lower Anterior Resection. AB - PURPOSE: The purpose of this study was to explore the prevalence of fecal incontinence (FI) and its impact on health-related quality of life in rectal cancer patients following low anterior resection surgery for colorectal cancer. DESIGN: Descriptive, cross-sectional study. SUBJECTS AND SETTING: Patients who were diagnosed with rectal cancer and underwent low anterior resection were recruited from a 1264-bed hospital in southern Taiwan. Potential participants were mailed a questionnaire survey. They were followed up 8 to 16 months postoperatively. Some clinical data were collected via retrospective review of their medical records. METHODS: Questionnaires were mailed to 172 patients, and 71 with colorectal cancer underwent low anterior resection and agreed to participate and completed questionnaires in the research, reflecting a return rate of 41%. Data were collected on demographic characteristics and disease related variables. Participants were asked if they had experienced FI during the past week. Fecal incontinence health-related quality of life was measured using the Cleveland Clinic Incontinence Score (CCIS) and the Fecal Incontinence Quality of Life Index. Completion of the questionnaire required approximately 15 minutes. RESULTS: More than half of the 71 participants (n = 45; 63.4%) experienced incontinence of flatus, 42.3% (n = 30) reported incontinence of liquid stool, and 14.1% (n = 10) stated that they experienced incontinence of solid stool. Based on mean CCIS scores, 35.2% (n = 25) experienced moderate to severe FI. One-third wore pads to contain FI and 21.1% changed daily activities because of FI. Nearly two-thirds reported FI during the week prior to completing the research questionnaire. The average Fecal Incontinence Quality of Life Index cumulative score was significantly lower in the FI group (2.62 +/- 0.61) than in the without FI group (3.32 +/- 0.77; P < .001), as were all subscale mean scores (all P < .01 .001). CONCLUSIONS: Fecal incontinence is prevalent among persons undergoing low anterior resection for colorectal cancer. Persons with FI report poor health related quality of life compared to persons who retained fecal continence. Health care providers should assess these patients for FI and treat or refer those who experience this common problem. PMID- 26135827 TI - Self-reported Prevalence of and Knowledge About Urinary Incontinence Among Community-Dwelling Israeli Women of Child-Bearing Age. AB - PURPOSE: The aim of this study was to examine the prevalence of urinary incontinence (UI) among parous women of child-bearing age and compare their level of knowledge regarding UI to those women without the condition. METHODS: A convenience sample of women aged 20 to 50 years who had given birth at least once completed questionnaires regarding (1) demographic information, (2) knowledge of UI (PIKQ-Prolapse and Incontinence Knowledge Quiz and PIKQ+), and (3) prevalence of UI (ICIQ-UI questionnaire-International Consultation on Incontinence Questionnaire-Urinary Incontinence short form). Women who were pregnant or 3 months or less postpartum were excluded from the analysis of the ICIQ-UI. RESULTS: Three hundred twenty-three women, representing 89.7% of those approached, participated in the study. Their mean age was 35.3 +/-5.0 years (mean +/- SD), all completed the knowledge questionnaire while 260 (80.5%) completed the UI questionnaire. Eighty-three (31.9%) suffered from UI, and most (67.5%) were between 31 and 40 years of age. Participants' level of knowledge about UI was found to be moderate (mean = 7.37 +/- 3.6) on the PIKQ+. Knowledge level was correlated with age (P = .017) and with higher levels of education (P < .001). There was a significantly higher level of UI knowledge (PIKQ+ scores) among women with UI (mean = 8.6; SD = 3.01) as compared to those who did not report UI (mean = 7.6; SD =+/-3.75; P < .001). CONCLUSION: Approximately one-third of parous women aged 20 to 50 years reported UI. Knowledge related to the condition tends to be moderate, increasing with higher age and education. PMID- 26135828 TI - Preparing for the Ostomy Certification Exam. PMID- 26135829 TI - Using Negative Pressure Therapy for Wound Healing in the Extremely Low-Birth Weight Infant (Micropreemie). AB - BACKGROUND: The term micropreemie describes an infant born weighing less than 1 pound 12 ounces (800 g) or before 26 weeks' gestation. The gastrointestinal tract of these premature infants is fragile due to developmental immaturity. In this case study, we describe our experience with wound care following surgical intervention for necrotizing enterocolitis in a micropreemie. CASE: Baby A is a female who was born at 23 weeks 5 days; she weighed 530 g. On day 12 of life, a sonogram was interpreted as suspicious for intestinal perforation. She underwent exploratory laparotomy with ileal perforation resection and stoma formation. A patch made from porcine small intestine submucosa was used to close the abdomen and negative pressure therapy using an open cell reticulated black foam was placed to assist with wound healing and decrease the need for frequent dressing changes. CONCLUSION: Our experience with this case demonstrates the feasibility of negative pressure wound therapy in selected micropreemie infants. Negative pressure therapy was effective in wound closure and decreased the number of dressing changes anticipated using conventional wound care. PMID- 26135831 TI - Implementation of a Bowel Management Program in Critical Care. PMID- 26135832 TI - European protocols for the diagnosis and initial treatment of interstitial lung disease in children. AB - Interstitial lung disease in children (chILD) is rare, and most centres will only see a few cases/year. There are numerous possible underlying diagnoses, with specific and non-specific treatment possibilities. The chILD-EU collaboration has brought together centres from across Europe to advance understanding of these considerations, and as part of this process, has created standard operating procedures and protocols for the investigation of chILD. Where established consensus documents exist already, for example, for the performance of bronchoalveolar lavage and processing of lung biopsies, these have been adopted. This manuscript reports our proposals for a staged investigation of chILD, starting from when the condition is suspected to defining the diagnosis, using pathways dependent on the clinical condition and the degree of illness of the child. These include the performance of genetic testing, echocardiography, high resolution CT, bronchoscopy when appropriate and the definitive investigation of lung biopsy, in order to establish a precise diagnosis. Since no randomised controlled trials of treatment have ever been performed, we also report a Delphi consensus process to try to harmonise treatment protocols such as the use of intravenous and oral corticosteroids, and add-on therapies such as hydroxychloroquine and azithromycin. The aim is not to dictate to clinicians when a therapeutic trial should be performed, but to offer the possibility to collaborators of having a unified approach when a decision to treat has been made. PMID- 26135833 TI - The British Thoracic Society guidelines on the investigation and management of pulmonary nodules. AB - The British Thoracic Society guideline for the investigation and management of pulmonary nodules is published as a supplement to this edition of the journal. It provides recommendations for the management of an individual with single or multiple pulmonary nodules and is a comprehensive reference text. PMID- 26135834 TI - Upregulation of microRNA-138-5p inhibits pancreatic cancer cell migration and increases chemotherapy sensitivity. AB - The present study investigated the role of microRNA (miR)-138-5p in regulating carcinoma migration and sensitivity to chemotherapy in pancreatic cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression levels of miR-138-5p in pancreatic cancer cell lines and primary carcinoma tissues from human patients. A lentiviral vector, containing miR-138-5p mimics (lv-miR-138-m) or miR-138-5p inhibitor (lv-miR-138-i), was used to either upregulate or downregulate the expression levels of miR-138-5p in PANC-1 cells, respectively. The effects of miR-138-3p regulation on pancreatic cancer cell migration and sensitivity to chemotherapy were examined. The predicted targeting of miR-138-5p on vimentin (VIM) was assessed by western blotting in PANC-1 cells. VIM was subsequently downregulated using small interfering (si)RNA to determine its effect on miR-138-5p-modulated pancreatic cancer cell development. The expression levels of miR-138-5p were downregulated in pancreatic cancer cell lines and primary carcinoma tissues. In PANC-1 cells, lentivirus-mediated upregulation of miR-138-5p inhibited cancer cell migration and increased cell chemosensitivity to 5-fluorouracil (5-FU). By contrast, downregulation of miR-138 5p promoted cancer cell migration and decreased cell chemosensitivity to 5-FU. A luciferase assay revealed that VIM was a direct target of miR-138-5p. Western blotting demonstrated that VIM was downregulated upon the upregulation of miR-138 5p in PANC-1 cells. siRNA-mediated downregulation of VIM inhibited pancreatic cancer cell migration in the control and miR-138-5p downregulated PANC-1 cells. The present study demonstrated that miR-138-5p is important in regulating pancreatic cancer development, possibly through targeting VIM. PMID- 26135836 TI - A Role for the Calcitonin Receptor to Limit Bone Loss During Lactation in Female Mice by Inhibiting Osteocytic Osteolysis. AB - During lactation, the large transfer of calcium from the mother to the milk is primarily sourced from the maternal skeleton. To determine whether the calcitonin receptor (CTR) plays a physiological role to protect the skeleton from excessive resorption during lactation, we assessed the maternal skeleton of global CTR knockout (CTRKO) and littermate control mice at the end of lactation (postnatal day 21). Micro-computed tomography analyses showed no effect on trabecular or cortical bone in the distal femur and L1 vertebra of maternal global CTR deletion at the end of lactation in global CTRKO mice compared with that in control mice. Bone resorption, as assessed by osteoclast number and activity at the end of lactation, was unaffected by maternal CTR deletion. Cathepsin K, carbonic anhydrase 2, matrix metalloproteinase 13, and receptor activator of nuclear factor-kappaB ligand mRNA levels, however, were markedly elevated by 3- to 6.5 fold in whole bone of lactating global CTRKO females. Because these genes have been shown to be up-regulated in osteocytes during lactation when osteocytes resorb their surrounding bone matrix, together with their reported expression of the CTR, we determined the osteocyte lacunar area in cortical bone. After lactation, the top 20% of osteocyte lacunar area in global CTRKO mice was 10% larger than the top 20% in control mice. These data are consistent with an increased osteocytic osteolysis in global CTRKO mice during lactation, which is further supported by the increased serum calcium observed in global CTRKO mice after lactation. These results provide evidence for a physiological role for the CTR to protect the maternal skeleton during lactation by a direct action on osteocytes to inhibit osteolysis. PMID- 26135835 TI - Loss of Bone and Wnt10b Expression in Male Type 1 Diabetic Mice Is Blocked by the Probiotic Lactobacillus reuteri. AB - Type 1 diabetes (T1D)-induced osteoporosis is characterized by a predominant suppression of osteoblast number and activity, as well as increased bone marrow adiposity but no change in osteoclast activity. The fundamental mechanisms and alternative anabolic treatments (with few side effects) for T1D bone loss remain undetermined. Recent studies by our laboratory and others indicate that probiotics can benefit bone health. Here, we demonstrate that Lactobacillus reuteri, a probiotic with anti-inflammatory and bone health properties, prevents T1D-induced bone loss and marrow adiposity in mice. We further found that L. reuteri treatment prevented the suppression of Wnt10b in T1D bone. Consistent with a role for attenuated bone Wnt10b expression in T1D osteoporosis, we observed that bone-specific Wnt10b transgenic mice are protected from T1D bone loss. To examine the mechanisms of this protection, we focused on TNF-alpha, a cytokine up-regulated in T1D that causes suppression of osteoblast Wnt10b expression in vitro. Addition of L. reuteri prevented TNF-alpha-mediated suppression of Wnt10b and osteoblast maturation markers. Taken together, our findings reveal a mechanism by which T1D causes bone loss and open new avenues for use of probiotics to benefit the bone. PMID- 26135837 TI - External control of reactions in microdroplets. AB - Scale reduction of chemical reactions enables novel screening and synthesis approaches that facilitate a highly parallelized and combinatorial exploration of chemical space. Droplet-based microfluidics have evolved as a powerful platform to allow many chemical reactions within small volumes that each can be controlled and manipulated. A significant technical challenge is the ability to change the concentration of reactants inside a droplet. Here we describe a strategy that relies on the use of reactants that are soluble in both oil and water and allow a passive, diffusive exchange of reactants between the oil and aqueous phases to externally control composition of the droplets. We demonstrate the applicability of our approach by externally changing the pH inside microdroplets without the need for physical manipulation or droplet merging. PMID- 26135838 TI - Knockdown of ADAM10 inhibits migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease with high rates of morbidity and mortality. Previous studies proposed that the A disintegrin and metalloprotease (ADAM) family is involved in the regulation of inflammation and arthritis. Thus, the present study investigated whether ADAM10 is involved in the progression of RA. The effects of ADAM10 small interfering (si)RNA on the expression levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8 and chemokine (C-X-C motif) ligand 16 (CXCL16) were determined in fibroblast-like synoviocytes (FLS). In addition, the effects of ADAM10 siRNA on cell proliferation, invasion and migration in human RA-FLS were assessed in vitro. The therapeutic efficacy and side-effects of ADAM10 siRNA were examined in a mouse model of collagen-induced arthritis (CIA). In vitro, ADAM10 silencing suppressed the expression of TNF-alpha, IL-6, IL-8 and CXCL16 in lipopolysaccharide (LPS) stimulated human RA-FLS. LPS-induced RA-FLS proliferation, migration and invasion were significantly attenuated by ADAM10 knockdown. ADAM10 silencing inhibited the secretion of vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase (MMP)-3 and -9 from LPS-stimulated human RA-FLS, in addition to inhibiting the phosphoinositide 3-kinase/AKT activation in LPS-stimulated human RA-FLS. In vivo, treatment with siRNA against ADAM10 for three weeks reduced the arthritis score. Serum levels of VEGF-A, MMP-3 and MMP-9 were also reduced in CIA mice. These observations indicate that the inhibition of ADAM10 may be a viable therapeutic target in the amelioration of disease progression in RA by attenuating FLS proliferation, migration and invasion. PMID- 26135839 TI - Bottom-up fabrication of graphene on Ru(0001) via molecular self-assembly. AB - A bottom-up fabrication of graphene via molecular self-assembly of p-Terphenyl on Ru(0001) has been investigated by scanning tunneling microcopy and density functional theory. Upon annealing of the sample at 450 degrees C, the intermediate stage is observed, in which the adsorbed p-Terphenyl molecules and graphitized flakes converted from the molecules coexist, implying the onset of dehydrogenation of p-Terphenyl. At the annealing temperature of 480 degrees C, the graphitized flakes start to convert into graphene. An adsoption energy of 5.99 eV is calculated for an individual p-Terphenyl molecule on Ru(0001), denoting a strong interaction between the adsorbate and substrate. The intermolecular interaction brings an extra adsorption energy of 0.28 eV for each molecule in the di-molecule adsorption system. During the conversion process from adsorbed molecule into graphene, the intermolecular interaction leads to the increase of the dehydrogenation barrier from 1.52 to 1.64 eV. PMID- 26135840 TI - Ionic liquid flow along the carbon nanotube with DC electric field. AB - Liquid pumping can occur along the outer surface of an electrode under a DC electric field. For biological applications, a better understanding of the ionic solution pumping mechanism is required. Here, we fabricated CNT wire electrodes (CWEs) and tungsten wire electrodes (TWEs) of various diameters to assess an ionic solution pumping. A DC electric field created by a bias of several volts pumped the ionic solution in the direction of the negatively biased electrode. The resulting electro-osmotic flow was attributed to the movement of an electric double layer near the electrode, and the flow rates along the CWEs were on the order of picoliters per minute. According to electric field analysis, the z directional electric field around the meniscus of the small electrode was more concentrated than that of the larger electrode. Thus, the pumping effect increased as the electrode diameter decreased. Interestingly in CWEs, the initiating voltage for liquid pumping did not change with increasing diameter, up to 20 MUm. We classified into three pumping zones, according to the initiating voltage and faradaic reaction. Liquid pumping using the CWEs could provide a new method for biological studies with adoptable flow rates and a larger 'Recommended pumping zone'. PMID- 26135841 TI - Cognitive function in preschool children with sleep-disordered breathing. AB - PURPOSE: The purposes of this study were to assess cognitive functions in preschool children with sleep-disordered breathing (SDB) and to compare them with matched control children. METHODS: A clinical sample of 2.5- to 6-year-old children with SDB was recruited. All children underwent sleep clinical record (SCR), which is a polysomnography (PSG)-validated questionnaire for diagnosing SDB, a polysomnography and a neurocognitive assessment. Normal controls were recruited from a kindergarten. They underwent the SCR and the cognitive assessment. RESULTS: We studied 41 children with primary snoring (PS)-mild obstructive sleep apnea syndrome (OSAS; M/F = 15/26, mean age 4.43 +/- 0.94), 36 children with moderate-severe OSAS (M/F = 22/14, mean age 4.33 +/- 1.02), and 83 controls (M/F = 33/50, mean age 4.5 +/- 0.64). In the two groups, no differences were found in duration and age of onset of SDB, while a significant difference emerged in SCR score (p < 0.005). No differences emerged in the three groups in Verbal IQ, Performance IQ, and Global IQ scores, nor in any cognitive subtests. CONCLUSIONS: We demonstrated that SDB of all severities is not associated with cognitive impairment compared to the control group in preschool age. PMID- 26135842 TI - Sleep disordered breathing in preschool children; still smart but for how long? PMID- 26135843 TI - Cellular Ubc2/Rad6 E2 ubiquitin-conjugating enzyme facilitates tombusvirus replication in yeast and plants. AB - Mono- and multi-ubiquitination alters the functions and subcellular localization of many cellular and viral proteins. Viruses can co-opt or actively manipulate the ubiquitin network to support viral processes or suppress innate immunity. Using yeast (Saccharomyces cerevisiae) model host, we show that the yeast Rad6p (radiation sensitive 6) E2 ubiquitin-conjugating enzyme and its plant ortholog, AtUbc2, interact with two tombusviral replication proteins and these E2 ubiquitin conjugating enzymes could be co-purified with the tombusvirus replicase. We demonstrate that TBSV RNA replication and the mono- and bi-ubiquitination level of p33 is decreased in rad6Delta yeast. However, plasmid-based expression of AtUbc2p could complement both defects in rad6Delta yeast. Knockdown of UBC2 expression in plants also decreases tombusvirus accumulation and reduces symptom severity, suggesting that Ubc2p is critical for virus replication in plants. We provide evidence that Rad6p is involved in promoting the subversion of Vps23p and Vps4p ESCRT proteins for viral replicase complex assembly. PMID- 26135844 TI - Control of the Pore Texture in Nanoporous Silicon via Chemical Dissolution. AB - The surface and textural properties of porous silicon (pSi) control many of its physical properties essential to its performance in key applications such as optoelectronics, energy storage, luminescence, sensing, and drug delivery. Here, we combine experimental and theoretical tools to demonstrate that the surface roughness at the nanometer scale of pSi can be tuned in a controlled fashion using partial thermal oxidation followed by removal of the resulting silicon oxide layer with hydrofluoric acid (HF) solution. Such a process is shown to smooth the pSi surface by means of nitrogen adsorption, electron microscopy, and small-angle X-ray and neutron scattering. Statistical mechanics Monte Carlo simulations, which are consistent with the experimental data, support the interpretation that the pore surface is initially rough and that the oxidation/oxide removal procedure diminishes the surface roughness while increasing the pore diameter. As a specific example considered in this work, the initial roughness xi ~ 3.2 nm of pSi pores having a diameter of 7.6 nm can be decreased to 1.0 nm following the simple procedure above. This study allows envisioning the design of pSi samples with optimal surface properties toward a specific process. PMID- 26135845 TI - Safety of Adult Ambulatory Direct Laryngoscopy: Revisits and Complications. AB - IMPORTANCE: Direct laryngoscopy, once an inpatient procedure, is now commonly performed in the outpatient setting. To ensure that safety follows the adoption of novel techniques and practice patterns, it is important to analyze the complication and revisit rates of these ambulatory surgery practices. OBJECTIVE: To determine revisit rates and complications after ambulatory adult direct laryngoscopy procedures. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional analysis of cases of adult patients who had undergone a direct laryngoscopic procedure extracted from multistate ambulatory surgery and hospital databases (State Ambulatory Surgery Databases for New York, Florida, Iowa, and California for 2010 and 2011). The analysis was performed on December 1, 2014. Index cases were linked to the corresponding State Emergency Department Databases and the State Inpatient Databases for visit encounters occurring within a 7-day postoperative window. All index cases were ambulatory surgery, without overnight stay or 23-hour observation. PARTICIPANTS: Adult patients who had undergone a direct laryngoscopy procedure. EXPOSURES: Direct laryngoscopy performed in an ambulatory setting. Patients who underwent flexible laryngoscopy, lesion destruction, laryngectomy, cordectomy, or a secondary nonlaryngoscopy procedure were specifically excluded. MAIN OUTCOMES AND MEASURES: Data regarding sex, age, revisit occurrence with associated complications, and mortality were analyzed. RESULTS: A total of 7743 cases of ambulatory laryngoscopy were identified (mean age, 60.4 years; 61% were male). The 7-day revisit rate was 3.0% (232 revisits). Serious airway complications occurred in 0.27% of cases (n = 21) and accounted for 9.1% of revisits. The rates of other major complications and minor complications were 0.15% (n = 12) and 0.75% (n = 58), respectively. There were no cases of anoxic brain injury. Two deaths occurred at the time of the revisit (7-day mortality rate, 0.03%; 95% CI, 0.01% 0.09%). CONCLUSIONS AND RELEVANCE: Adult ambulatory direct laryngoscopy has a favorable safety profile. Serious airway complications occur in fewer than 3 patients per 1000 cases. The risk of death following outpatient laryngoscopy is extremely low. Outpatient laryngoscopy is not universally suited for all patients, and careful preoperative selection and counseling are imperative. PMID- 26135846 TI - Activation of CO by Hydrogenated Magnesium(I) Dimers: Sterically Controlled Formation of Ethenediolate and Cyclopropanetriolate Complexes. AB - This study details the formal hydrogenation of two magnesium(I) dimers {(Nacnac)Mg}2 (Nacnac = [{(C6H3R2-2,6)NCMe}2CH](-); R = Pr(i) ((Dip)Nacnac), Et ((Dep)Nacnac)) using 1,3-cyclohexadiene. These reactions afford the magnesium(II) hydride complexes, {(Nacnac)Mg(MU-H)}2. Their reactions with excess CO are sterically controlled and lead cleanly to different C-C coupled products, viz. the ethenediolate complex, ((Dip)Nacnac)Mg{kappa(1)-O-[((Dip)Nacnac)Mg(kappa(2) O,O-O2C2H2)]}, and the first cyclopropanetriolate complex of any metal, cis {((Dep)Nacnac)Mg}3{MU-C3(H3)O3}. Computational studies imply the CO activation processes proceed via very similar mechanisms to those previously reported for related reactions involving f-block metal hydride compounds. This work highlights the potential magnesium compounds hold for use in the "Fischer-Tropsch-like" transformation of CO/H2 mixtures to value added oxygenate products. PMID- 26135847 TI - Fatal case of hemolytic-uremic syndrome in an adult due to a rare serogroup O91 Entero hemorrhagic Escherichia coli associated with a Clostridium difficile infection. More than meets the eye. AB - Hemolytic-uremic syndrome due to enterohemorrhagic Escherichia coli, belonging to serogroup O91 has rarely been described. We report here a case of post-diarrheal HUS due to EHEC O91 in an elderly patient for whom diagnosis was delayed given a previously diagnosed C. difficile infection. This case highlights the usefulness of Shiga-toxin detection. PMID- 26135848 TI - Epidemiological burden of invasive pneumococcal disease in children and adolescents with predisposing risk factors. AB - OBJECTIVE: Some medical conditions constitute important risk factors for the development of invasive pneumococcal diseases in children and adolescents aged from 5 to 19 years. Conjugate vaccines have potential efficacy in this scenario, but are not available in many Latin American public healthcare systems for this age group. This study aimed to estimate the preventable fraction of invasive pneumococcal diseases among individuals aged from 5 to 19 years with associated risk factors for its development. METHODS: Data regarding the Latin America population, risk factors prevalence and conjugate vaccines efficacy were obtained from the literature. RESULTS: Total population at risk ranged from 17.3 to 64.6 million of individuals and asthma was the most impacting risk factor. According to SIREVA, PCV13 provided a 62.9% serotypes coverage in individuals from 5 to 29 years in 2012, potentially increasing the covered population from [8,338,457 31,057,620] with PCV10 to [10,906,356-40,622,078] with PCV13. To date, according to available efficacy data, the hypothetically immunized population ranged from 11.4 to 42.4 million, representing 7.0% to 26.0% of the total population in this age group. CONCLUSIONS: Vaccination in risk groups should be encouraged, as it potentially contributes to the reduction in the number of cases of invasive pneumococcal disease. PMID- 26135849 TI - One-year swallowing outcomes following transoral laser microsurgery +/- adjuvant therapy versus primary chemoradiotherapy for advanced stage oropharyngeal squamous cell carcinoma. AB - OBJECTIVES: To assess the between-group change in swallowing function from baseline to 12 months following treatment, for patients treated for resectable stage III and IVA oropharyngeal squamous cell carcinoma. To assess the within group change in swallowing function between 3 and 12 months following treatment. DESIGN: Non-randomised cohort study. SETTING: A single head and neck cancer unit with oncology services held at the nearby regional treatment centre. PARTICIPANTS: Twenty-five patients treated with Transoral Laser Microsurgery +/- adjuvant (chemo)radiotherapy (Transoral Laser Microsurgery) observed alongside an historic cohort of 33 patients treated with (chemo)radiotherapy. MAIN OUTCOME MEASURES: The patient reported MD Anderson Dysphagia Inventory (MDADI), an objective timed Water Swallow Test, and the clinician rated normalcy of diet subsection of the Performance of Swallowing Scale . RESULTS: Between baseline and 12 months, patients treated with primary (chemo)radiotherapy demonstrated greater deterioration in swallowing function compared to Transoral Laser Microsurgery for all 3 swallowing measures. Between 3 and 12 months, the only significant change was an improvement in Performance of Swallowing Scale scores in the (chemo)radiotherapy group. CONCLUSIONS: This is the first study to report the results of a complimentary set of swallowing measures for patients treated with Transoral Laser Microsurgery, observed alongside a cohort of (chemo)radiotherapy patients. The preliminary results suggest a benefit in swallowing function for Transoral Laser Microsurgery over (chemo)radiotherapy during the year following treatment. PMID- 26135850 TI - KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells. AB - Karyopherin-alpha2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. We investigated the function and possible mechanisms of KPNA2 involved in rheumatoid arthritis (RA). Western blotting and immunohistochemistry showed the protein expression of KPNA2 increased in synovial tissue of RA patients compared with the healthy controls. Double immunofluorescent staining indicated that KPNA2 co-localized with T cells, macrophage-like synoviocytes, fibroblast-like synoviocytes, and neutrophils in synovial tissue of RA patients. Moreover, the expression of KPNA2 in SW982 cells was increased in a time-dependent manner in response to TNFalpha stimulation. Both Western blotting and immunofluorescent staining assay revealed the co localization of KPNA2 and P65 and their translocation from cytoplasma in TNFalpha treated SW982 cells. Furthermore, knocking down the expression of KPNA2 by siRNA inhibited TNFalpha-induced expression of IL-6, MMP-1, and MMP-13 and, more importantly, decreased the P65 phosphorylation in SW982 cells. We therefore suggested that KPNA2 may play a key role in the inflammation process of RA via NF kappaB P65 signal transduction pathway. PMID- 26135851 TI - Chitosan-coated red fluorescent protein nanoparticle as a potential dual functional siRNA carrier. AB - AIMS: Developing safe and efficient nano vectors is critical for the success of siRNA therapy. MATERIALS & METHODS: By encapsulating red fluorescent protein (RFP) with chitosan (CS), a dual-functional siRNA delivery nano vector, RFP@CS, has been synthesized. RESULTS: RFP@CS has an optimum size of 7-23 nm for siRNA delivery; and the fluorescence of RFP, protected by CS coating, provides an excellent probe to track the delivery of siRNA. RFP@CS delivers siRNA efficiently into cells and the targeted gene could be completely silenced even after 48 h. No cytotoxicity or acute toxicity in mice was observed. CONCLUSION: The high transfection efficacy and safety demonstrate RFP@CS is a promising nano vector for the gene therapy. PMID- 26135852 TI - Structural features and near infra-red (NIR) luminescence of isomeric Yb(III) bipyridyl-N,N'-dioxide coordination polymers. AB - The synthesis and structural characterization of a series of lanthanide complexes formed from YbX3 salts (X = NO3(-) or CF3SO3(-)) and the isomeric 4,4'-bipyridine N,N'-dioxide (4,4'-bpdo) or 3,3'-bipyridine-N,N'-dioxide (3,3'-bpdo) ligands has been undertaken by X-ray crystallography. Depending on the choice of anion, the complexes isolated with L = 4,4'-bpdo yield either an extended 1D linear chain {[Yb(L)(NO3)3(CH3OH)]}infinity or a coordination polymer network {[Yb(L)4](CF3SO3)3}infinity which are isostructural with previously reported compounds using other Ln(iii) metals. The isomeric 3,3'-bpdo ligand yields a similar extended 1D linear chain {[Yb(L)(NO3)3(CH3OH)]}infinity when NO3(-) is used as the anion. However, when substituted by the typically non-coordinating CF3SO3(-) anion, inner sphere coordination yields a coordination polymer {[Yb(L)3(CF3SO3)](CF3SO3)2}infinity with a (2(2).4(8).6(5)) network topology. In an effort to rationalize the observed difference in coordinating behavior, DFT calculations of the isomeric bipyridyl-N,N'-dioxide ligands have been undertaken, but revealed no significant differences in the charge distribution of the coordinating N-oxide groups. Lastly, sensitized Yb(iii) emission in the Near Infra-Red (NIR) region operating via the well-known antennae effect has been observed and compared for two of the coordination polymers. PMID- 26135853 TI - Effects of personality on the opioidergic modulation of the emotion warmth liking. AB - Neurobiological research suggests there are discrete emotion systems, which are based on separate neural pathways with specific neurotransmitters (i.e., oxytocin, opioids). So far, autonomic regulation patterns of different positive emotions could not be unambiguously characterized. Warmth-liking, as an emotion system, is activated during interpersonal interactions and close relationships. We postulated that warmth-liking has a specific somatovisceral signature, which is, however, qualified by individual differences in personality and attachment style. Individual differences in personality and attachment style are postulated to contribute to MU-opiate functioning. Forty-eight females in a heterosexual relationship, selected on the basis of attachment reports, took part in a virtual ball-tossing game with their partners and two confederates. Participants received either the competitive MU-opioid antagonist naltrexone (25 mg) or a placebo in a randomized double-blind design. Social exclusion during the game reduced feelings of warmth, increased feelings of anger, and increased blood pressure and left ventricular contractibility, whereas social inclusion was characterized by physiological quiescence. Further analyses revealed differential effects in self reported feelings as well as in cardiovascular parameters as a function of attachment style. Secure attachment predicted higher levels of warmth-liking, physiological quiescence, and less negative feelings even during social exclusion. These findings can be interpreted as evidence for psychophysiological resilience. Furthermore, naltrexone reduced feelings of warmth and increased vasoconstriction during social inclusion, especially for securely bonded participants. These findings are remarkable hints for an opioidergic modulation of the interaction between emotion and personality. PMID- 26135855 TI - Systems Biology Research into Cardiovascular Disease: Contributions of Lipidomics based Approaches to Biomarker Discovery. AB - Atherosclerosis is a progressive inflammatory thickening of the arterial wall resulting from increased cellularity and the accumulation of lipids, cellular debris, and extracellular matrix. Conventional determinations of plasma lipoproteins have resulted in a wealth of clinical data documenting the correlation between low- and high-density lipoproteins (LDL and HDL) and cardiovascular disease (CVD) risk. Current mass spectrometry methodologies allow the detection and quantification of multiple molecular lipid species with various structural and functional roles. The opportunities provided by lipidomics for lipid-based biomarker discovery are prominent in disease diagnostics, monitoring of drug efficacy, and translational model development. For example, the analysis of human plasma samples assessing the effects of statins has shown correlative effects between the LDL/HDL ratio and sphingomyelin and phosphatidylcholine. Additionally, at the vascular tissue level, lipids from different classes are enriched in human plaques of coronary arteries and in the aortas of apolipoprotein E-deficient mice exposed to cigarette smoke, highlighting a set of lipid biomarkers for translational research. Molecular lipidomics will provide insights in which other lipids may play important roles in vascular disease progression and will serve as novel markers for preventive as well as therapeutic purposes. PMID- 26135856 TI - Reliability of Virtual Screening Methods in Prediction of PDE4B-inhibitor Activity. AB - Identification of active ligands using computational methods is a challenging task. For example, molecular docking, pharmacophore modeling, and three dimensional quantitative structure-activity relationship models (3D-QSAR) are widely used methods to identify novel small molecules. However, all these methods have, in addition to advantages, also significant pitfalls. The aim of this study was to compare some commonly used computational methods to estimate their ability to separate highly active PDE4B-inhibitors from less active and inactive ones. Here, 152 molecules with pIC50-range of 3.4-10.5, originating from six original studies were used. High correlation coefficients by using docking, docking with postprocessing with molecular mechanics-generalized Born-surface area -method (MMGBSA), pharmacophore modeling, and 3D-QSAR were obtained. These results are well in line with earlier studies done with similar methods, and suggest that computational methods could be successfully used to identify novel PDE4B inhibitors, especially if using multiple methods together. PMID- 26135854 TI - Arachidonic acid-derived signaling lipids and functions in impaired healing. AB - Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT(-/-) mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs. The latter suggests excess coagulation and potentially increased platelet aggregation. We show here that in these impaired wounds there is an imbalance in the arachidonic acid (AA) derived eicosonoids that mediate or modulate inflammatory reactions and platelet aggregation. In the LIGHT(-/-) impaired wounds there is a significant increase in enzymatically derived breakdown products of AA. We found that early after injury there was a significant increase in the eicosanoids 11-, 12-, and 15-hydroxyeicosa-tetranoic acid, and the proinflammatory leukotrienes (LTD4 and LTE) and prostaglandins (PGE2 and PGF2alpha ). Some of these eicosanoids also promote platelet aggregation. This led us to examine the levels of other eicosanoids known to be involved in the latter process. We found that thromboxane (TXA2 /B2 ), and prostacyclins 6kPGF1alpha are elevated shortly after wounding and in some cases during healing. To determine whether they have an impact in platelet aggregation and hemostasis, we tested LIGHT(-/-) mouse wounds for these two parameters and found that, indeed, platelet aggregation and hemostasis are enhanced in these mice when compared with the control C57BL/6 mice. Understanding lipid signaling in impaired wounds can potentially lead to development of new therapeutics or in using existing nonsteroidal anti-inflammatory agents to help correct the course of healing. PMID- 26135857 TI - Discovery Approaches for Novel Dyslipidemia Drugs. AB - INTRODUCTION: Dyslipidemia is increased fasting level of total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG), along with decreased levels of HDL cholesterol (HDL-C). Owing to effect on the cardiovascular system and increased chances of metabolic diseases, it is needed to review novel under development drugs and new approaches in drug discovery for dyslipidemia. AREAS COVERED: This article reviews all phases I to IV clinical trials and preclinical trials with results associated with novel treatment of dyslipidemia. Drug discovery for dyslipidemia, toward newer targets has been addressed. FINDINGS: Statins are, currently available, best choice of drugs for treating dyslipidemia and coronary diseases. In addition to this, lipid lowering drugs support treatment to a great extent, either as monotherapy or in combinations with other groups. Pravastatin used in combination with cholesteryl ester, transfers protein inhibitors (CETP) to produce efficient results. Peroxisome proliferator-activated receptor agonists (PPAR) like muraglitazar, aleglitazar and tesaglitazar are PPAR alpha/gamma receptor agonist, dual in action performs better in phase 3 clinical study and reduces renal and cardiovascular events. By targeting both receptors, a better treatment for cardiovascular and diabetic problems can be achieved. Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors like humanized monoclonal antibodies, are newly discovered inhibitors that reduce the risk of cardiovascular diseases. During the past few years, nucleic acid-based therapies targeting lipid and lipoprotein metabolism, such as microsomal TG transfer protein (MTP) may be a promising therapeutic approach to treat vascular diseases. Gene regulating transcription factors involved in bile acids and cholesterol metabolism can be controlled by FXR agonists in dyslipidemia. To overcome these drawbacks, many thyroid hormone analogues have been developed to lower down cholesterol level by targeting specifically thyroid hormone beta receptors abundantly present in the liver without severe side effects. Virtual screening, an important tool in screening databases of the lead compounds, provides a good platform to access new compounds. In this review, examples of novel FXR modulators, thyromimetic agents, cholesterol absorption inhibitors and other new anti hyperlipidemia scaffolds have been addressed. PMID- 26135858 TI - Antimicrobial Treatment Options for Granulomatous Mastitis Caused by Corynebacterium Species. AB - Corynebacterium species are increasingly recognized as important pathogens in granulomatous mastitis. Currently, there are no published treatment protocols for Corynebacterium breast infections. This study describes antimicrobial treatment options in the context of other management strategies used for granulomatous mastitis. Corynebacterium spp. isolated from breast tissue and aspirate samples stored from 2002 to 2013 were identified and determined to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), 16S RNA sequencing, and rpoB gene targets. The MICs for 12 antimicrobials were performed using Etest for each isolate. Correlations of these with antimicrobial characteristics, choice of antimicrobial, and disease outcome were evaluated. Corynebacterium spp. from breast tissue and aspirate samples were confirmed in 17 isolates from 16 patients. Based on EUCAST breakpoints, Corynebacterium kroppenstedtii isolates (n = 11) were susceptible to seven antibiotic classes but resistant to beta-lactam antibiotics. Corynebacterium tuberculostearicum isolates (n = 4) were multidrug resistant. Two nonlipophilic species were isolated, Corynebacterium glucuronolyticum and Corynebacterium freneyi, both of which have various susceptibilities to antimicrobial agents. Short-course antimicrobial therapy was common (median, 6 courses per subject; range, 1 to 9 courses). Patients with C. kroppenstedtii presented with a hot painful breast mass and underwent multiple surgical procedures (median, 4 procedures; range, 2 to 6 procedures). The management of Corynebacterium breast infections requires a multidisciplinary approach and includes culture and appropriate sensitivity testing to guide antimicrobial therapy. Established infections have a poor outcome, possibly because adequate concentrations of some drugs will be difficult to achieve in lipophilic granulomata. Lipophilic antimicrobial therapy may offer a therapeutic advantage. The role of immunotherapy has not been defined. PMID- 26135859 TI - Comparison between Salmonella enterica Serotype Enteritidis Genotyping Methods and Phage Type. AB - A quantitative comparison between discriminatory indexes and concordance among multilocus variable-number tandem-repeat analysis (MLVA), pulsed-field gel electrophoresis (PFGE), automated ribotyping, and phage typing has been performed, testing 238 Salmonella enterica serotype Enteritidis isolates not epidemiologically correlated. The results show that MLVA is the best choice, but each typing method provides a piece of information for establishing clonal relationships between the isolates. PMID- 26135860 TI - Tracking Nosocomial Klebsiella pneumoniae Infections and Outbreaks by Whole Genome Analysis: Small-Scale Italian Scenario within a Single Hospital. AB - Multidrug-resistant (MDR) Klebsiella pneumoniae is one of the most important causes of nosocomial infections worldwide. After the spread of strains resistant to beta-lactams at the end of the previous century, the diffusion of isolates resistant to carbapenems and colistin is now reducing treatment options and the containment of infections. Carbapenem-resistant K. pneumoniae strains have spread rapidly among Italian hospitals, with four subclades of pandemic clonal group 258 (CG258). Here we show that a single Italian hospital has been invaded by three of these subclades within 27 months, thus replicating on a small scale the "Italian scenario." We identified a single clone responsible for an epidemic outbreak involving seven patients, and we reconstructed its star-like pattern of diffusion within the intensive care unit. This epidemiological picture was obtained through phylogenomic analysis of 16 carbapenem-resistant K. pneumoniae isolates collected in the hospital during a 27-month period, which were added to a database of 319 genomes representing the available global diversity of K. pneumoniae strains. Phenotypic and molecular assays did not reveal virulence or resistance determinants specific for the outbreak isolates. Other factors, rather than selective advantages, might have caused the outbreak. Finally, analyses allowed us to identify a major subclade of CG258 composed of strains bearing the yersiniabactin virulence factor. Our work demonstrates how the use of combined phenotypic, molecular, and whole-genome sequencing techniques can help to identify quickly and to characterize accurately the spread of MDR pathogens. PMID- 26135862 TI - Two Cases of Urinary Tract Infection Caused by Propionimicrobium lymphophilum. AB - The first case reports involving Propionimicrobium lymphophilum, a rarely encountered anaerobic Gram-positive non-spore-forming rod, are presented here as urinary tract infections. Initial detection of these bacteria required urine Gram stains. Comparison of the type strain to the two isolates by various methods is depicted and includes antimicrobial susceptibility data. PMID- 26135861 TI - Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements. AB - The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and internal transcript spacer), and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were detected only in low numbers. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed saturation after 50 patients were analyzed. In contrast to bacteria, a large number of fungal species were observed together with high fluctuations over time and among patients. These findings demonstrated that the mycobiome was dominated by transient species, which strongly suggested that the main driving force was their presence in inhaled air rather than colonization. Considering the high exposure of human airways to fungal spores, we concluded that fungi have low colonization abilities in CF, and colonization by pathogenic fungal species may be considered a rare event. A comprehensive understanding of the conditions promoting fungal colonization may offer the opportunity to prevent colonization and substantially reduce or even eliminate fungus-related disease progression in CF. PMID- 26135863 TI - Molecular Epidemiology of Novel Pathogen "Brachyspira hampsonii" Reveals Relationships between Diverse Genetic Groups, Regions, Host Species, and Other Pathogenic and Commensal Brachyspira Species. AB - Outbreaks of bloody diarrhea in swine herds in the late 2000s signaled the reemergence of an economically significant disease, swine dysentery, in the United States. Investigations confirmed the emergence of a novel spirochete in swine, provisionally designated "Brachyspira hampsonii," with two genetically distinct clades. Although it has since been detected in swine and migratory birds in Europe and North America, little is known about its genetic diversity or its relationships with other Brachyspira species. This study characterizes B. hampsonii using a newly developed multilocus sequence typing (MLST) approach and elucidates the diversity, distribution, population structure, and genetic relationships of this pathogen from diverse epidemiological sources globally. Genetic characterization of 81 B. hampsonii isolates, originating from six countries, with our newly established MLST scheme identified a total of 20 sequence types (STs) belonging to three clonal complexes (CCs). B. hampsonii showed a heterogeneous population structure with evidence of microevolution locally in swine production systems, while its clustering patterns showed associations with its epidemiological origins (country, swine production system, and host species). The close genetic relatedness of B. hampsonii isolates from different countries and host species highlights the importance of strict biosecurity control measures. A comparative analysis of 430 isolates representing seven Brachyspira species (pathogens and commensals) from 19 countries and 10 host species depicted clustering by microbial species. It revealed the close genetic relatedness of B. hampsonii with commensal Brachyspira species and also provided support for the two clades of B. hampsonii to be considered a single species. PMID- 26135864 TI - Disseminated Balamuthia mandrillaris Infection. AB - Balamuthia mandrillaris is a rare cause of human infection, but when infections do occur, they result in high rates of morbidity and mortality. A case of disseminated Balamuthia infection is presented. Early diagnosis and initiation of recommended therapy are essential for increased chances of successful outcomes. PMID- 26135865 TI - Defining and Evaluating a Core Genome Multilocus Sequence Typing Scheme for Whole Genome Sequence-Based Typing of Listeria monocytogenes. AB - Whole-genome sequencing (WGS) has emerged today as an ultimate typing tool to characterize Listeria monocytogenes outbreaks. However, data analysis and interlaboratory comparability of WGS data are still challenging for most public health laboratories. Therefore, we have developed and evaluated a new L. monocytogenes typing scheme based on genome-wide gene-by-gene comparisons (core genome multilocus the sequence typing [cgMLST]) to allow for a unique typing nomenclature. Initially, we determined the breadth of the L. monocytogenes population based on MLST data with a Bayesian approach. Based on the genome sequence data of representative isolates for the whole population, cgMLST target genes were defined and reappraised with 67 L. monocytogenes isolates from two outbreaks and serotype reference strains. The Bayesian population analysis generated five L. monocytogenes groups. Using all available NCBI RefSeq genomes (n = 36) and six additionally sequenced strains, all genetic groups were covered. Pairwise comparisons of these 42 genome sequences resulted in 1,701 cgMLST targets present in all 42 genomes with 100% overlap and >=90% sequence similarity. Overall, >=99.1% of the cgMLST targets were present in 67 outbreak and serotype reference strains, underlining the representativeness of the cgMLST scheme. Moreover, cgMLST enabled clustering of outbreak isolates with <=10 alleles difference and unambiguous separation from unrelated outgroup isolates. In conclusion, the novel cgMLST scheme not only improves outbreak investigations but also enables, due to the availability of the automatically curated cgMLST nomenclature, interlaboratory exchange of data that are crucial, especially for rapid responses during transsectorial outbreaks. PMID- 26135866 TI - Phaeohyphomycosis Caused by a Novel Species, Pseudochaetosphaeronema martinelli. AB - Among the opportunistic mycoses that are emerging in patients with immunosuppression or severe underlying illness, many isolates lack of characteristic sporulation and until recently could not be identified. Clinical signs are mostly nonspecific and therefore such infections have often been disregarded. In the present paper we describe a novel, nonsporulating fungal species causing subcutaneous phaeohyphomycosis in two patients of different origin. One is a 73-year-old female from Martinique who suffered from rheumatoid arthritis, while the other case concerns a 72-year-old male from Mexico who had a history of type 2 diabetes mellitus. Sequencing of the partial ribosomal operon revealed that in both cases a member of the order Pleosporales was concerned which could not be affiliated to any family within this order. Multilocus analysis revealed that the fungus was related to another, unaffiliated agent of human mycetoma, Pseudochaetosphaeronema larense, and therefore the name Pseudochaetosphaeronema martinelli was introduced. PMID- 26135867 TI - Use of Alignment-Free Phylogenetics for Rapid Genome Sequence-Based Typing of Helicobacter pylori Virulence Markers and Antibiotic Susceptibility. AB - Whole-genome sequencing is becoming a leading technology in the typing and epidemiology of microbial pathogens, but the increase in genomic information necessitates significant investment in bioinformatic resources and expertise, and currently used methodologies struggle with genetically heterogeneous bacteria such as the human gastric pathogen Helicobacter pylori. Here we demonstrate that the alignment-free analysis method feature frequency profiling (FFP) can be used to rapidly construct phylogenetic trees of draft bacterial genome sequences on a standard desktop computer and that coupling with in silico genotyping methods gives useful information for comparative and clinical genomic and molecular epidemiology applications. FFP-based phylogenetic trees of seven gastric Helicobacter species matched those obtained by analysis of 16S rRNA genes and ribosomal proteins, and FFP- and core genome single nucleotide polymorphism-based analysis of 63 H. pylori genomes again showed comparable phylogenetic clustering, consistent with genomotypes assigned by using multilocus sequence typing (MLST). Analysis of 377 H. pylori genomes highlighted the conservation of genomotypes and linkage with phylogeographic characteristics and predicted the presence of an incomplete or nonfunctional cag pathogenicity island in 18/276 genomes. In silico analysis of antibiotic susceptibility markers suggests that most H. pylori hspAmerind and hspEAsia isolates are predicted to carry the T2812C mutation potentially conferring low-level clarithromycin resistance, while levels of metronidazole resistance were similar in all multilocus sequence types. In conclusion, the use of FFP phylogenetic clustering and in silico genotyping allows determination of genome evolution and phylogeographic clustering and can contribute to clinical microbiology by genomotyping for outbreak management and the prediction of pathogenic potential and antibiotic susceptibility. PMID- 26135868 TI - Mycoplasma hominis, a Rare but True Cause of Infective Endocarditis. AB - Mycoplasma spp. are rarely recognized agents of infective endocarditis. We report a case of Mycoplasma hominis prosthetic valve endocarditis diagnosed by 16S ribosomal DNA (rDNA) PCR and culture of valves in a 74-year-old man. We reviewed the literature and found only 8 other cases reported. PMID- 26135869 TI - Comparison of Three Commercial Molecular Assays for Detection of Rifampin and Isoniazid Resistance among Mycobacterium tuberculosis Isolates in a High-HIV Prevalence Setting. AB - In a head-to-head comparison of the MTBDRplus version 2.0 (Hain Lifescience), the Xpert MTB/RIF (Cepheid), and the Anyplex MTB/NTM (Seegene) assays, we demonstrated equal sensitivity (59/61; 96.7%) and specificity (53/54; 98.1%) for detecting rifampin resistance with further analysis of discordances. The Xpert assay does not detect isoniazid resistance while the Anyplex assay showed high false positivity. PMID- 26135870 TI - Characterization of Third-Generation-Cephalosporin-Resistant Shiga Toxin Producing Strains of Escherichia coli O157:H7 in Japan. AB - We isolated Shiga toxin-producing Escherichia coli O157:H7 strains resistant to third-generation cephalosporins. The resistant strains harbored blaCMY-2, a plasmid-mediated AmpC beta-lactamase. Genotyping of isolates revealed the possible spread of this problematic bacterium. Results suggested the importance of the investigation and surveillance of enterobacteria with plasmids harboring blaCMY-2. PMID- 26135871 TI - Emergence of Serotype IV Group B Streptococcus Adult Invasive Disease in Manitoba and Saskatchewan, Canada, Is Driven by Clonal Sequence Type 459 Strains. AB - Serotype IV group B Streptococcus (GBS) is emerging in Canada and the United States with rates as high as 5% of the total burden of adult invasive GBS disease. To understand this emergence, we studied the population structure and assessed the antimicrobial susceptibility of serotype IV isolates causing adult invasive infection in Manitoba and Saskatchewan, Canada, between 2010 and 2014. Whole-genome sequencing was used to determine multilocus sequence typing information and identify genes encoding antimicrobial resistance in 85 invasive serotype IV GBS strains. Antimicrobial susceptibility testing was performed by standard methods. Strain divergence was assessed using genome-wide single nucleotide polymorphism analysis. Serotype IV strains were responsible for 16.9% of adult invasive GBS infections in Manitoba and Saskatchewan during the period. The majority of serotype IV isolates (89%) were clonally related, tetracycline-, erythromycin-, and clindamycin-resistant sequence type 459 (ST459) strains that possessed genes tetM and ermTR. Genome comparisons between ST459 and serotype V ST1 GBS identified several areas of recombination in an overall similar genomic background. Serotype IV ST459 GBS strains are expanding and causing a substantial percentage of adult invasive GBS disease. This emergence may be linked to the acquisition of resistance to tetracycline, macrolides, and lincosamides. PMID- 26135873 TI - Temporal Variation in Viral Hemorrhagic Septicemia Virus Antibodies in Freshwater Drum (Aplodinotus grunniens) Indicates Cyclic Transmission in Lake Winnebago, Wisconsin. AB - Viral hemorrhagic septicemia virus (VHSV) is an emerging pathogen that causes mass mortality in multiple fish species. In 2007, the Great Lakes freshwater strain, type IVb, caused a large die-off of freshwater drum (Aplodinotus grunniens) in Lake Winnebago, Wisconsin, USA. To evaluate the persistence and transmission of VHSV, freshwater drum from Lake Winnebago were tested for antibodies to the virus using recently developed virus neutralization (VN) and enzyme-linked immunosorbent (ELISA) assays. Samples were also tested by real-time reverse transcription-PCR (rRT-PCR) to detect viral RNA. Of 548 serum samples tested, 44 (8.03%) were positive by VN (titers ranging from 1:16 to 1:1,024) and 45 (8.21%) were positive by ELISA, including 7 fish positive by both assays. Antibody prevalence increased with age and was higher in one northwestern area of Lake Winnebago than in other areas. Of 3,864 tissues sampled from 551 fish, 1 spleen and 1 kidney sample from a single adult female fish collected in the spring of 2012 tested positive for VHSV by rRT-PCR, and serum from the same fish tested positive by VN and ELISA. These results suggest that VHSV persists and viral transmission may be active in Lake Winnebago even in years following outbreaks and that wild fish may survive VHSV infection and maintain detectable antibody titers while harboring viral RNA. Influxes of immunologically naive juvenile fish through recruitment may reduce herd immunity, allow VHSV to persist, and drive superannual cycles of transmission that may sporadically manifest as fish kills. PMID- 26135872 TI - Genotypic Tropism Testing in HIV-1 Proviral DNA Can Provide Useful Information at Low-Level Viremia. AB - The possibility of performing genotypic tropism testing (GTT) with proviral DNA (pvDNA) even during suppressed viremia would facilitate the use of CCR5 inhibitors as part of switching, simplification, or intensification strategies. Thus, we aimed to evaluate the tropism concordance between plasma RNA and pvDNA samples and to assess which factors could affect possible discrepancies between the two compartments. GTT was performed using both plasma RNA and pvDNA from 55 sample pairs from drug-experienced patients. Potential differences between the two compartments were evaluated by analyzing coreceptor usage and genetic variability. Paired samples were also stratified in three levels of viremia (<50, 51 to 500, and >500 copies/ml). Overall, Geno2Pheno comparisons of false-positive rates in the two compartments showed good correlation (r = 0.72). A high level of concordance in tropism predictions for the two compartments was found (46/55 sample pairs [83.6%]). Among the 9 sample pairs with discordant tropisms, a larger proportion of pvDNA samples harboring CXCR4/dual-mixed-tropic viruses was found, in comparison with plasma RNA samples (88.9% versus 11.1%; P = 0.0034). Discordant samples were characterized by greater genetic variability than were concordant samples. With stratification of the paired samples according to viremia levels, the prevalence of discordant samples decreased with increasing viremia (<50 copies/ml, 21.4%; 51 to 500 copies/ml, 15.4%; >500 copies/ml, 6.7%; P = 0.2). Our findings confirm that prediction of viral tropism using pvDNA is feasible even in low-level viremia and provides useful information for therapy optimization for patients with low or suppressed viremia. PMID- 26135874 TI - Impact of Mutations at Amino Acid 70 in Hepatitis C Virus (HCV) Genotype 1b Core Region on Hepatocarcinogenesis following Eradication of HCV RNA. AB - The impact of the HCV genotype 1b core amino acid (aa) 70 mutant on the cumulative rate of hepatocellular carcinoma following eradication of HCV RNA by antiviral therapy was investigated with the Q-Invader assay. Multivariate analysis based on 649 patients indicated that a core aa70 Q-Invader mutant level >=20% is a predictor of hepatocellular carcinoma. PMID- 26135875 TI - Development and Validation of Two Screening Assays for the Hepatitis C Virus NS3 Q80K Polymorphism Associated with Reduced Response to Combination Treatment Regimens Containing Simeprevir. AB - Persons with hepatitis C virus (HCV) genotype 1a (GT1a) infections harboring a baseline Q80K polymorphism in nonstructural protein 3 (NS3) have a reduced virologic response to simeprevir in combination with pegylated interferon-alfa and ribavirin. We aimed to develop, validate, and freely disseminate an NS3 clinical sequencing assay to detect the Q80K polymorphism and potentially other HCV NS3 drug resistance mutations. HCV RNA was extracted from frozen plasma using a NucliSENS easyMAG automated nucleic acid extractor, amplified by nested reverse transcription-PCR, and sequenced using Sanger and/or next-generation (MiSeq) methods. Sanger chromatograms were analyzed using in-house software (RECall), and nucleotide mixtures were called automatically. MiSeq reads were iteratively mapped to the H77 reference genome, and consensus NS3 sequences were generated with nucleotides present at >20% called as mixtures. The accuracy, precision, and sensitivity for detecting the Q80K polymorphism were assessed in 70 samples previously sequenced by an external laboratory. A comparison of the sequences generated by the Sanger and MiSeq methods with those determined by an external lab revealed >98.5% nucleotide sequence concordance and zero discordant calls of the Q80K polymorphism. The results were both highly repeatable and reproducible (>99.7% nucleotide concordance and 100% Q80K concordance). The limits of detection (>2 and ~5 log10 IU/ml for the Sanger and MiSeq assays, respectively) are sufficiently low to allow genotyping in nearly all chronically infected treatment-naive persons. No systematic bias in the under- or overamplification of minority variants was observed. Coinfection with other viruses (e.g., HIV and hepatitis B virus [HBV]) did not affect the assay results. The two independent HCV NS3 sequencing assays with the automated analysis procedures described here are useful tools to screen for the Q80K polymorphism and other HCV protease inhibitor drug resistance mutations. PMID- 26135876 TI - Ceftaroline Activity against mecC-Containing Staphylococcus aureus. PMID- 26135877 TI - Coinfection with "Rickettsia sibirica subsp. mongolotimonae" and Rickettsia conorii in a Human Patient: a Challenge for Molecular Diagnosis Tools. AB - Rickettsioses are zoonoses transmitted by vectors. More than one agent can coexist in vectors. Although vectors may transmit more than one microorganism to humans, information on dual infections is scarce. We present a case of a patient with an atypical rickettsiosis diagnosis in whom two species of Rickettsia were detected. PMID- 26135878 TI - Modelling the physiological strain and physical burden of chemical protective coveralls. AB - This study determined the impact of selected chemical protective coveralls (CPC) on physiological responses and comfort sensations. Fifteen males exercised at approximately 6 METS in three CPC (Tyvek(r), Gulf and Tychem(r)) and a control garment. Physiological strain was characterised by core and skin temperatures, heart rate, VO2, perceived exertion, hotness and wetness. Physical burden was characterised by restriction to movement, VO2 and RPE. The highest levels of physiological strain and physical burden were found in Tychem(r), and the lowest in control. Seven statistical regression models were developed through correlation and multiple regression analyses between the human responses and the results from previously conducted fabric and garment property testing. These models showed that physical burden was increased by adding weight and/or restricting movement. Oxygen consumption was best predicted by clothing weight and fabric bending hysteresis. Fabric evaporative resistance and thickness were the two best predictors of physiological and perceptual responses. Practitioner Summary: Traditional evaluation of chemical protective coveralls (CPC) involves testing at the fabric and garment levels and rarely is based on human trials. This study integrates information from fabric, garment and human trials to better understand physiological strain and physical comfort during prolonged exercise in CPC. PMID- 26135879 TI - Films of bacteria at interfaces: three stages of behaviour. AB - We report an investigation of the formation of films by bacteria at an oil-water interface using a combination of particle tracking and pendant drop elastometry. The films display a remarkably varied series of dynamical and mechanical properties as they evolve over the course of minutes to hours following the creation of an initially pristine interface. At the earliest stage of formation, which we interrogate using dispersions of colloidal probes, the interface is populated with motile bacteria. Interactions with the bacteria dominate the colloidal motion, and the interface displays canonical features of active matter in a quasi-two-dimensional context. This active stage gives way to a viscoelastic transition, presumably driven by the accumulation at the interface of polysaccharides and surfactants produced by the bacteria, which instill the interface with the hallmarks of soft glassy rheology that we characterize with microrheology. Eventually, the viscoelastic film becomes fully elastic with the capability to support wrinkling upon compression, and we investigate this final stage with the pendant drop measurements. We characterize quantitatively the dynamic and mechanical properties of the films during each of these three stages active, viscoelastic, and elastic - and comment on their possible significance for the interfacial bacterial colony. This work also brings to the forefront the important role that interfacial mechanics may play in bacterial suspensions with free surfaces. PMID- 26135880 TI - Response to Letter to the Editor, "Effectiveness of Implant Therapy Analyzed in a Swedish Population: Early and Late Implant Loss". PMID- 26135881 TI - Letter to the Editor, "Effectiveness of Implant Therapy Analyzed in a Swedish Population: Early and Late Implant Loss". PMID- 26135883 TI - Fluorescence-guided surgery of human prostate cancer experimental bone metastasis in nude mice using anti-CEA DyLight 650 for tumor illumination. AB - The present report demonstrates efficacy of fluorescence-guided surgery (FGS) to resect and prevent recurrence of experimental skeletal metastasis in a nude-mouse model of human prostate cancer. Green fluorescent protein (GFP)-expressing PC-3 human prostate cancer cells were injected into the intramedullary cavity of the tibia in 25 nude mice. One week after implantation, monoclonal antibodies, specific for carcinoembryonic antigen (CEA), labeled with DyLight 650, were injected into the tail vein of 13 mice. Thirteen mice underwent FGS and 12 mice underwent bright-light surgery (BLS). Weekly GFP fluorescence imaging of the mice was performed to observe tumor recurrence. The extent of residual tumor after BLS was 13-fold greater than after FGS (p < 0.001). Time-course imaging visualized rapid growth of the residual tumor in the BLS group, whereas the FGS group showed only slight tumor growth and significantly improved disease-free survival of the treated mice. Our study demonstrated that FGS significantly reduced residual tumor as well as the recurrence of experimental prostate-cancer bone metastasis. The present results suggest that FGS will be effective for resection of skeletal metastases in selected patients with prostate cancer. PMID- 26135882 TI - Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR-124 and anxiety. AB - BACKGROUND: Lack of physical activity and increased levels of stress contribute to the development of multiple physical and mental disorders. An increasing number of studies relate voluntary exercise with greater resilience to psychological stress, a process that is highly regulated by the hypothalamic pituitary-adrenal (HPA) axis. However, the molecular mechanisms underlying the beneficial effects of exercise on stress resilience are still poorly understood. Here we have studied the impact of long term exercise and housing conditions on: a) hippocampal expression of glucocorticoid receptor (Nr3c1), b) epigenetic regulation of Nr3c1 (DNA methylation at the Nr3c1-1F promoter and miR-124 expression), c) anxiety (elevated plus maze, EPM), and d) adrenal gland weight and adrenocorticotropic hormone receptor (Mc2r) expression. RESULTS: Exercise increased Nr3c1 and Nr3c1-1F expression and decreased miR-124 levels in the hippocampus in single-housed mice, suggesting enhanced resilience to stress. The opposite was found for pair-housed animals. Bisulfite sequencing showed virtually no DNA methylation in the Nr3c1-1F promoter region. Single-housing increased the time spent on stretch attend postures. Exercise decreased the time spent at the open arms of the EPM, however, the mobility of the exercise groups was significantly lower. Exercise had opposite effects on the adrenal gland weight of single and pair-housed mice, while it had no effect on adrenal Mc2r expression. CONCLUSIONS: These results suggest that exercise exerts a positive impact on stress resilience in single-housed mice that could be mediated by decreasing miR 124 and increasing Nr3c1 expression in the hippocampus. However, pair-housing reverses these effects possibly due to stress from dominance disputes between pairs. PMID- 26135884 TI - Expert's comment concerning Grand Rounds case entitled "Antepartum surgical management of Pott's paraplegia along with maintenance of pregnancy during second trimester" (by R. Kaul et al. doi:10.1007/s00586-015-4045-4). PMID- 26135885 TI - Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice. AB - AIMS: To determine the effects and underlying molecular mechanisms of caloric restriction (CR) in C57BL/6 mice. METHODS: Thirty-six 6-week-old male C57BL/6 mice were assigned to a normal control group (NC, n=12), a high energy group (HE, n=12), and a CR group (n=12), and received a normal diet, a high-calorie diet, or a calorie-restricted diet, respectively, for 44 weeks. Body weight and serum glucose concentration were regularly recorded, and animals were sacrificed and hippocampus tissues were collected for immunohistochemistry (n=6 per group), western blotting (n=3 per group) and real-time polymerase chain reaction (n=3 per group) analysis at the end of the 44-week experimental period. Immunohistochemistry, western blotting and real-time polymerase chain reaction were used to detect changes in hippocampal proteins may be involved in the SIRT1/mTOR pathways. RESULTS: Body weight and serum glucose over the 44 weeks in animals from the CR group were lower than those of HE group. The number of SIRT1 immunoreactive cells in the CR group was significantly higher than in the NC and HE groups, and SIRT1 mRNA expression in the CR group was significantly higher than that in the HE group, but there was no difference in SIRT1 protein expression among the three groups. mTOR and S6K1 protein activation and mTOR and S6K1 mRNA were significantly lower in the CR group than in the NC group. CONCLUSIONS: Our findings suggest that a CR diet could lead to activation of SIRT1 and suppression of mTOR and S6K1 activation in C57BL/6 mice. We have shown that the SIRT1/mTOR signaling pathways may be involved in the neuroprotective effect of CR. PMID- 26135887 TI - Pedometers Affect Changes in Lower-Extremity Physical Function During a Square Stepping Exercise Program in Older Japanese Adults. AB - BACKGROUND AND PURPOSE: Pedometers are often used as motivational tools to increase physical activity. Hence, providing a pedometer during an exercise intervention may enhance the benefit of exercise on lower-extremity physical function (LEPF) by maintaining or increasing daily physical activity. The purpose of this study was to compare the effect on LEPF between an exercise intervention with and without the use of a pedometer. METHODS: The subjects of this study were 68 community-dwelling older adults (mean age: 70.0 +/- 3.6 years) in Kasama City, rural Japan. All subjects participated in a fall-prevention exercise program called square-stepping exercise (SSE) conducted once a week for 11 weeks. Participants were allocated to 2 groups: SSE with pedometer group (n = 34) and SSE without pedometer group (n = 34). We matched the participants of both groups by their standardized score of physical function tests. To ascertain the LEPF benefits induced by the exercise intervention, we measured 5 physical function tests: single-leg balance with eyes open, 5-repetition sit-to-stand, timed up and go, 5-m habitual walk, and choice stepping reaction time. We used a 2-way analysis of variance to confirm the interaction between the 2 groups. RESULTS: Significant group-by-time interactions were observed on timed up and go (P < .01) and 5-m habitual walk (P = .02); participants in the SSE with pedometer group enhanced their physical function more than the SSE without pedometer group participants. CONCLUSIONS: This study suggests that providing a pedometer during an exercise intervention is an effective addition to an exercise program to improve LEPF. PMID- 26135886 TI - Effects of diacerein on cartilage and subchondral bone in early stages of osteoarthritis in a rabbit model. AB - BACKGROUND: Osteoarthritis is thought to be the most prevalent chronic and disabling joint disease in animals and humans. At present, there is no ideal treatment option. The aim of this study was to assess the effects of the treatment with oral diacerein on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of osteoarthritis by micro-CT evaluation and histological analysis. To this purpose, osteoarthritis was surgically induced on one knee of 16 rabbits using the contralateral knee as healthy controls. Treatment was started three weeks later and lasted eight weeks. Animals were divided into two groups for treatment: Placebo (treated daily with oral saline) and diacerein (treated orally with 1.5 mg/kg/day of diacerein). RESULTS: Sample analysis revealed that this model induced osteoarthritis in the operated knee joint. Osteoarthritis placebo group showed a significant increase in non-calcified cartilage thickness and volume with respect to the control placebo group and important changes in the synovial membrane; whereas the parameters measured in subchondral bone remained unchanged. In the osteoarthritis diacerein-treated group the results showed an improvement with respect to the OA placebo group in all parameters, although the results were not statistically significant. CONCLUSION: The results of this animal study suggested that the diacerein treatment for OA may be able to ameliorate the swelling and surface alterations of the cartilage and exert an anti-inflammatory effect on the synovial membrane, which might contribute to OA improvement, as well as an anabolic effect on subchondral trabecular bone. PMID- 26135888 TI - Control of climate and litter quality on leaf litter decomposition in different climatic zones. AB - Climate and initial litter quality are the major factors influencing decomposition rates on large scales. We established a comprehensive database of terrestrial leaf litter decomposition, including 785 datasets, to examine the relationship between climate and litter quality and evaluate the factors controlling decomposition on a global scale, the arid and semi-arid (AS) zone, the humid middle and humid low (HL) latitude zones. Initial litter nitrogen (N) and phosphorus (P) concentration only increased with mean annual temperature (MAT) in the AS zone and decreased with mean annual precipitation (MAP) in the HL zone. Compared with nutrient content, MAT imposed less effect on initial litter lignin content than MAP. MAT were the most important decomposition driving factors on a global scale as well as in different climatic zones. MAP only significantly affected decomposition constants in AS zone. Although litter quality parameters also showed significant influence on decomposition, their importance was less than the climatic factors. Besides, different litter quality parameters exerted significant influence on decomposition in different climatic zones. Our results emphasized that climate consistently exerted important effects on decomposition constants across different climatic zones. PMID- 26135890 TI - Response to 'Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis'--authors' reply. PMID- 26135889 TI - Myeloid Sirtuin 2 Expression Does Not Impact Long-Term Mycobacterium tuberculosis Control. AB - Sirtuins (Sirts) regulate several cellular mechanisms through deacetylation of several transcription factors and enzymes. Recently, Sirt2 was shown to prevent the development of inflammatory processes and its expression favors acute Listeria monocytogenes infection. The impact of this molecule in the context of chronic infections remains unknown. We found that specific Sirt2 deletion in the myeloid lineage transiently increased Mycobacterium tuberculosis load in the lungs and liver of conditional mice. Sirt2 did not affect long-term infection since no significant differences were observed in the bacterial burden at days 60 and 120 post-infection. The initial increase in M. tuberculosis growth was not due to differences in inflammatory cell infiltrates in the lung, myeloid or CD4+ T cells. The transcription levels of IFN-gamma, IL-17, TNF, IL-6 and NOS2 were also not affected in the lungs by Sirt2-myeloid specific deletion. Overall, our results demonstrate that Sirt2 expression has a transitory effect in M. tuberculosis infection. Thus, modulation of Sirt2 activity in vivo is not expected to affect chronic infection with M. tuberculosis. PMID- 26135891 TI - Scoping Review of Research on the Effectiveness of Food-Safety Education Interventions Directed at Consumers. AB - Improper food handling by consumers at home is a major cause of foodborne illness. Therefore, effective education strategies are essential to change consumers' food safety attitudes and behaviors. The purpose of this scoping review was to identify and characterize primary literature examining the effectiveness of consumer food-safety education interventions. Ten bibliographic databases were searched using a comprehensive search strategy. Citations were identified; two reviewers screened them for relevance and characterized relevant articles. To ensure results would be applicable to end users, stakeholders were engaged to provide input on the review scope, methods, and results. We identified 246 relevant articles, of which 150 were quantitative, 66 qualitative, and 30 mixed-method research studies. Most studies (64.2%) were published in the United States, using an uncontrolled before-and-after study design (31.3%), and investigated the effectiveness of community-based training sessions and workshops (52.0%). Research gaps were found in the number of randomized controlled studies conducted, academic- and school-based courses and curricula investigated, and interventions targeting high-risk populations (e.g., pregnant women, those who are immunocompromised) and using new media channels (e.g., social media). Key opportunities to enhance the utility of future primary research investigating consumer food-safety interventions include the following: using studies based on behavior-change theories and formative research; engaging the target population in the research; using validated instruments to measures outcomes; and reporting intervention characteristics and outcomes completely. Results of this review can be used to prioritize future primary research and decision-making in this area. PMID- 26135892 TI - Extended-Spectrum beta-Lactamase (ESBL)-Producing Klebsiella pneumoniae in Bulk Tank Milk from Dairy Farms in Indonesia. AB - Bulk tank milk from 80 dairy farms located in the West Java Region of Indonesia was analyzed for the presence of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. Isolates from seven dairy farms were ESBL positive, and all were identified as Klebsiella pneumoniae. The isolates showed ESBL characteristic antibiotic resistance patterns. Further analysis revealed that all K. pneumoniae isolates harbored the blaSHV gene, and two isolates were additionally positive for the blaTEM-1 and blaCTX-M-15 genes. Isolates from different farms were clonally diverse according to macrorestriction analysis. The results indicate that the relatively high frequency of ESBL-producing K. pneumoniae in bulk tank milk implies the risk that milk is both a source of local exposure and a vector contributing to the supraregional spread of antibiotic resistant bacteria by trade. PMID- 26135893 TI - Reducing Colonization and Eggborne Transmission of Salmonella Enteritidis in Layer Chickens by In-Feed Supplementation of Caprylic Acid. AB - Salmonella Enteritidis (SE) is a major foodborne pathogen responsible for causing gastrointestinal infections in humans, predominantly due to the consumption of contaminated eggs. In layer hens, SE colonizes the intestine and migrates to various organs, including the oviduct, thereby leading to egg yolk and shell contamination. This study investigated the efficacy of caprylic acid (CA), a medium-chain fatty acid, in reducing SE colonization and egg contamination in layers. Caprylic acid was supplemented in the feed at 0%, 0.7%, or 1% (vol/wt) from day 1 of the experiment. Birds were challenged with 10(10) log colony forming units (CFU)/mL of SE by crop gavage on day 10, and re-inoculated (10(10) log CFU/mL) on day 35. After 7 days post first inoculation, eggs were collected daily and tested for SE on the shell and in the yolk separately. The birds were sacrificed on day 66 to determine SE colonization in the ceca, liver, and oviduct. The consumer acceptability of eggs was also determined by triangle test. The experiment was replicated twice. In-feed supplementation of CA (0.7% and 1%) to birds consistently decreased SE on eggshell and in the yolk (p<0.05). Supplementation of CA at 1.0% decreased SE population to ~14% on the shell and ~10% in yolk, when compared to control birds, which yielded ~60% positive samples on shell and ~43% in yolk. Additionally, SE populations in the cecum and liver were reduced in treated birds compared to control (p<0.05). No significant difference in egg production, body weight, or sensory properties of eggs was observed (p>0.05). The results suggest that CA could potentially be used as a feed additive to reduce eggborne transmission of SE. PMID- 26135894 TI - Extended-Spectrum beta-Lactamase, AmpC-Producing, and Fluoroquinolone-Resistant Escherichia coli in Retail Broiler Chicken Meat, Italy. AB - BACKGROUND: Globally, antimicrobial drug-resistant Escherichia coli is among the most common etiological agents of invasive disease in humans. In Europe, increasing proportions of infections due to third-generation cephalosporins and/or fluoroquinolone-resistant extraintestinal pathogenic E. coli (ExPEC) strains are reported. E. coli from poultry are those more closely linked to human E. coli, but lack of reliable data makes it difficult to assess the attributable risk of different food sources. In the present study, our objective was to investigate the antimicrobial resistance profile, phylogenetic background, and virulence factors of E. coli isolates from broiler chicken meat sold at retail in Palermo, Italy. MATERIALS AND METHODS: Isolation of multidrug resistant (MDR) E. coli was performed during April-December 2013 on a total of 163 chicken meat samples. Susceptibility to a panel of nine antimicrobial agents was determined. PCR assays were carried out to detect extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase, and plasmid-mediated quinolone resistance (PMQR) genes, phylogenetic group, and ExPEC-associated traits. A single nucleotide polymorphism (SNP) PCR was done to detect E. coli sequence type (ST)131. RESULTS: One hundred thirty-four isolates from 109 meat samples were MDR. B1 was the most prevalent phylogenetic group (47.8%), followed by groups D (25.4%), A (22.3%), and B2 (4.5%). ESBLs and AmpC beta-lactamases were detected by PCR in 132 (98.5%) and 15 (11.2%) isolates. PMQR determinants were detected in 122 (91%) isolates. Twenty-two MDR isolates met the molecular definition of ExPEC. SNP-PCR results confirmed that four B2 isolates were ST131. Enterobacterial Repetitive Intergenic Consensus sequence-PCR analysis showed a large heterogeneity with 55 unique profiles and 31 clusters including 2-4 isolates. CONCLUSIONS: An alarmingly high prevalence of MDR E. coli from broiler chicken meat is evident in our geographic area. The ongoing use of antimicrobial drugs in livestock should be urgently restricted, particularly in the poultry sector. PMID- 26135895 TI - Decreased Resistance to Broad-Spectrum Cephalosporin in Escherichia coli from Healthy Broilers at Farms in Japan After Voluntary Withdrawal of Ceftiofur. AB - The high prevalence of broad-spectrum cephalosporin (BSC) resistance in Escherichia coli isolates from healthy broilers at farms is a source of grave concern in Japan. In an effort to solve this problem, the off-label use of ceftiofur (CTF) at hatcheries was voluntarily withdrawn around March 2012. The objective of this study was to assess the effect of the voluntary withdrawal on the prevalence of BSC resistance in E. coli from healthy broilers at farms. A total of 693 E. coli isolates collected from 362 fecal samples of healthy broilers at farms between 2010 and 2013 were examined to determine their antimicrobial resistance profiles and beta-lactamase genes. beta-Lactamase genes were characterized by polymerase chain reaction and sequencing. BSC resistance was detected in 84 of the 693 E. coli isolates (12.1%) from healthy broilers between 2010 and 2013. The percentage of BSC-resistant E. coli isolates was significantly decreased: from 16.4% (32/195) in 2010 and 16.8% (27/161) in 2011 to 9.2% (19/206) in 2012 and 4.6% (6/131) in 2013 (2010 versus 2012: p=0.024, 2010 versus 2013: p=0.001, 2011 versus 2012: p=0.038, and 2011 versus 2013: p=0.001). Regarding beta-lactamase genes, 58 of the 84 BSC-resistant E. coli isolates (69.0%) harbored blaCMY-2. The prevalence of BSC resistance in E. coli isolated from healthy broilers at farms was markedly decreased within a year after the voluntary withdrawal from CTF use at hatcheries. This indicates that BSC resistance in E. coli isolates from broilers could be controlled by restricting the use of CTF at the hatchery level. PMID- 26135896 TI - Systemic inflammation score predicts postoperative prognosis of patients with clear-cell renal cell carcinoma. AB - BACKGROUND: Growing evidence indicates that inflammation has a crucial role in the development and progression of cancer. We developed a novel systemic inflammation score (SIS) based on preoperative serum albumin and lymphocyte-to monocyte ratio (LMR), and examined its prognostic value for patients with clear cell renal cell carcinoma (ccRCC) after surgery. METHODS: The study comprised 441 ccRCC patients undergoing nephrectomy between 2008 and 2009 in a single centre. The SIS was developed and its associations with clinicopathological features and overall survival (OS) were evaluated. RESULTS: The SIS consisted of serum albumin and LMR that were both retained as independent indicators adjusting for other haematological and laboratory markers of systemic inflammation responses and traditional clinicopathological features. A high SIS was significantly associated with aggressive tumour behaviours and served as an independent prognostic factor of reduced OS. Furthermore, the SIS could significantly stratify patient prognosis in different tumour stages and Mayo Clinic stage, size, grade and necrosis scores. Incorporation of the SIS into a prognostic model including TNM stage, Fuhrman grade and lymphovascular invasion generated a nomogram, which predicted accurately 3- and 5-year survival for ccRCC patients. CONCLUSIONS: The SIS as a potentially powerful prognostic biomarker might improve traditional clinicopathological analysis to refine clinical outcome prediction for ccRCC patients after surgery. PMID- 26135898 TI - Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome. AB - An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin((r)), Targiniq((r)), Targinact((r)); hereafter referred to as oxycodone/naloxone PR) is approved in Europe for the second-line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. Coadministration of naloxone represents a targeted approach to counteracting opioid-induced bowel dysfunction without compromising therapeutic efficacy; because of its very low oral bioavailability, naloxone blocks the action of oxycodone at opioid receptors locally in the gut. The efficacy of oxycodone/naloxone PR in patients with severe RLS inadequately controlled by previous (mainly dopaminergic) treatment has been demonstrated in RELOXYN, a 12-week, randomized, double-blind study with a 40-week open-label extension. In this pivotal study, oxycodone/naloxone PR significantly improved RLS symptoms compared with placebo from week 2 onwards; a beneficial effect of oxycodone/naloxone PR was maintained through 1 year of treatment. Furthermore, improvements in RLS symptoms in oxycodone/naloxone PR recipients were accompanied by similarly sustained improvements in disease-specific quality of life and subjective sleep variables. Oxycodone/naloxone PR was generally well tolerated, with a treatment-related adverse event profile (e.g. gastrointestinal disorders, CNS disorders, fatigue and pruritus) that was consistent with that expected for opioid therapy. Notably, there were no confirmed cases of augmentation among oxycodone/naloxone PR recipients throughout the course of the study. Results from the well-designed RELOXYN trial have thus demonstrated the value of oxycodone/naloxone PR as a second-line therapy for severe refractory RLS; further investigation of this combination product as a first-line treatment for severe RLS is now warranted. PMID- 26135897 TI - Overexpression of connexin 43 reduces melanoma proliferative and metastatic capacity. AB - BACKGROUND: Alterations in connexin 43 (Cx43) expression and/or gap junction (GJ) mediated intercellular communication are implicated in cancer pathogenesis. Herein, we have investigated the role of Cx43 in melanoma cell proliferation and apoptosis sensitivity in vitro, as well as metastatic capability and tumour growth in vivo. METHODS: Connexin 43 expression levels, GJ coupling and proliferation rates were analysed in four different human melanoma cell lines. Furthermore, tumour growth and lung metastasis of high compared with low Cx43 expressing FMS cells were evaluated in vivo using a melanoma xenograft model. RESULTS: Specific inhibition of Cx43 channel activity accelerated melanoma cell proliferation, whereas overexpression of Cx43 increased GJ coupling and reduced cell growth. Moreover, Cx43 overexpression in FMS cells increased basal and tumour necrosis factor-alpha-induced apoptosis and resulted in decreased melanoma tumour growth and lower number and size of metastatic foci in vivo. CONCLUSIONS: Our findings reveal an important role for Cx43 in intrinsically controlling melanoma growth, death and metastasis, and emphasise the potential use of compounds that selectively enhance Cx43 expression on melanoma in the future chemotherapy and/or immunotherapy protocols. PMID- 26135899 TI - Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells. AB - The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation and mineralization. In vitro aged hMSC developed a senescence associated secretory phenotype (SASP), resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1beta, CXCL1, CXCL2) expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1) induced SASP related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis. PMID- 26135900 TI - Epigenetic regulation in heart failure: part II DNA and chromatin. AB - Epigenetic regulatory mechanisms play key roles in cardiac development, differentiation, homeostasis, response to stress and injury, and disease. Human heart failure (HF) epigenetic regulatory mechanisms have not been deciphered to date. This 2-part review distills the rapidly evolving research focused on human HF epigenetic regulatory mechanisms. Part I, which was published in the September/October issue, focused on epigenetic regulatory mechanisms involving RNA, specifically the role of short, intermediate, and long noncoding RNAs (lncRNAs) and endogenous competing RNA regulatory networks. Part II, now in the November/December issue, focuses on the epigenetic regulatory mechanisms involving DNA, including DNA methylation, histone modifications, and chromatin conformational changes. Part II concludes with 2 examples of well-studied integrated epigenetic regulatory mechanisms: the structural and functional roles of the Mediator complex in regulating transcription and the epigenetic networked "cross-talk" regulating atrial natriuretic peptide and brain natriuretic peptide promoter activation. PMID- 26135901 TI - MicroRNAs in Cardiovascular Disease: Perspectives and Reality. AB - Since the discovery of the first noncoding RNA decades ago, the transcriptomics evolution has made a great leap reaching to the detection and recognition of microRNAs (miRNAs) in the early 1990s. Thereafter, numerous miRNAs were reported in different species, with a great body of literature focusing on their role in human health and in pathophysiological processes. miRNAs play a significant role in the cardiovascular system, not only in physiology and normal development but also in disease processes and evolution. Further studies on miRNAs have highlighted their participation in several expressions of cardiovascular disease, such as atherosclerosis, acute and chronic syndromes of coronary artery disease, heart failure, and cardiac arrhythmias. To date, the challenge remains to understand the underlying mechanisms of miRNAs that drive their expression profile so as to use them as innovative diagnostic tools or therapeutic targets in cardiovascular disease. PMID- 26135902 TI - Feasibility and outcome of the implementation of a screening program for panic disorder in noncardiac chest pain patients in cardiac emergency department routine care. AB - OBJECTIVE: This study assesses the feasibility and outcome of the implementation of a screening program for classifying panic disorder (PD) in patients presenting with noncardiac chest pain (NCCP(1)), when integrated in routine cardiac emergency department (CED(2)) care. METHODS: Barrier analyses were made during the pilot phase and implementation period. NCCP patients aged 18-70 years presenting at the CED (n=252) were eligible for screening with the Hospital Anxiety and Depression Scale (HADS). Those scoring above cutoff on the HADS were referred to the psychiatric department and received the Composite International Diagnostic Interview. RESULTS: Screening was initiated in 60 patients (23.8%), of whom nine refused participation. Staff adherence remained low despite implementing several improvements in the screening procedure. In total, 39 patients completed the program; 8 were diagnosed with a psychiatric disorder, including 2 patients with PD. CONCLUSION: Feasibility of implementation of this screening program for PD in NCCP patients in routine CED care was limited because offering screening frequently conflicted with provision of acute care and because patients showed relatively high refusal rates. Contrasting our assumption, various other psychiatric disorders besides PD were classified. PMID- 26135903 TI - Apelin-13 induces MCF-7 cell proliferation and invasion via phosphorylation of ERK1/2. AB - Apelin-13 is extensively expressed in various tissues, particularly breast tissue. Apelin-13 has been shown to promote tumor proliferation in various types of cancer, including hepatocellular, lung and ovarian cancer. However, the effect and molecular mechanism of apelin-13 in breast cancer cells remains unclear. The present study investigated the effect of apelin-13 on MCF-7. Therefore, cell proliferation was determined by MTT and flow cytometry analysis. The results revealed that apelin-13 markedly increased cell proliferation. Transwell assays demonstrated that apelin-13 increased MCF-7 cell invasion. Apelin-13 also markedly increased the expression of cyclin D1, extracellular matrix metalloproteinase-1 and amplified in breast cancer 1 (AIB1) in a dose-dependent manner by polymerase chain reaction assays. To study the molecular mechanism, cell proliferation, invasion and cyclin D1 were inhibited by pre-treatment with 10 uM of PD98059 (ERK(1/2) inhibitor). Western blotting results suggested that apelin-13 significantly enhances the expression of p-ERK(1/2) in a concentration dependent manner. In conclusion, the results suggest that apelin-13 promoted MCF 7 cell proliferation and invasion via the ERK1/2/AIB1 signaling pathway. PMID- 26135904 TI - A "keto-enol tautomerization"-based response mechanism: a novel approach to stimuli-responsive supramolecular gel. AB - A novel approach to stimuli-responsive gel termed the "keto-enol tautomerization" based response mechanism was proposed. By tautomerization, vinyl ketone-based gelator G3 can be self-assembled into an organogel (OG3) accompanied by strong AIE. OG3 shows reversible dual-channel response for S(2-). The response process is based on the reversible deprotonation of the enol moiety in the tautomerized gelator G3'. PMID- 26135905 TI - Mn(II)- and Co(II)-Catalyzed Transformation of 2-Cyanopyrimidine to Methylimidate by Sodium Azide: Isolation, Structural Characterization, and Magnetic Studies on 2D Mn(II)- and Cu(II)-Complexes. AB - The Mn(II)-mediated transformation of 2-cyanopyrimidine to methylimidate in the presence of inorganic azide is proven through isolation and structural characterization of a metal complex. Though the reaction conditions are favorable for a "click" reaction leading to the formation of tetrazole, as evidenced from recent studies, we are astonished to see the formation of methylimidate in MeOH instead of tetrazole, which is supposed to form only in the presence of catalytic amount of corresponding alkoxide ion as base. The catalytic nature of this transformation reaction was confirmed by performing these experiments under catalytic conditions and analyzing the products using liquid chromatography-mass spectrometry techniques, which clearly showed ~96% and ~60% selectivity of methylimidate along with almost 100% conversion in the presence of Mn(II) and Co(II) as catalysts, respectively. In absence or presence of other metal ions like Cu(II), Ni(II), Fe(II), Zn(II), etc. only tetrazole formation takes place. So the present findings extended the formation of methylimidate catalyzed by metal ions in the presence of azide ion in alcoholic medium. Importantly, a probable mechanism for this unexpected transformation was framed based on the structural analysis and high-resolution mass spectrometry (electrospray ionization MS(+)) studies. The magnetic studies were also performed on complexes [Mn(L)(N3)2]n (1) and [Cu (L(2))2]n (2a), showing anti-ferromagnetic character for compound 1 and negligible coupling for the copper complex 2a. PMID- 26135907 TI - Perceived Maternal Parenting Styles, Cultural Values, and Prosocial Tendencies Among Mexican American Youth. AB - The present study aimed to extend research on parenting and positive development of Latino youth. Participants were 207 Mexican American adolescents (M age = 10.9 years, SD = 0.83 years; 50% girls) who completed measures of their parents' supportive and firm parenting, their own endorsement of respect and traditional gender role values, and their tendency to engage in six forms of prosocial behaviors. Maternal nativity was also considered as an initial predictor of parenting, adolescents' cultural values, and adolescents' prosocial behaviors. Overall, the results demonstrated that maternal nativity was associated with traditional gender roles and specific forms of prosocial behaviors. Parenting dimensions were differentially associated with respect and traditional gender role values and prosocial behaviors. Cultural values, in turn, were associated with multiple forms of prosocial behaviors. Gender differences in the processes were also explored. PMID- 26135906 TI - Impaired Early Attentional Processes in Parkinson's Disease: A High-Resolution Event-Related Potentials Study. AB - INTRODUCTION: The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. A previous study using the P3 component of the event-related potentials suggested that a reduced ability to resist interference could be responsible for attention disorders at early stages of Parkinson's disease (PD), with a possible role of the dorsolateral prefrontal cortex (DLPFC). METHODS: Our objective was to better determine the origin of this impairment, by studying an earlier ERP component, the N2, and its subcomponents, as they reflect early inhibition processes and as they are known to have sources in the anterior cingulate cortex (ACC), which is involved together with the DLPFC in inhibition processes. Fifteen early-stage PD patients and 15 healthy controls (HCs) performed a three-stimulus visual oddball paradigm, consisting in detecting target inputs amongst standard stimuli, while resisting interference from distracter ones. A 128-channel electroencephalogram was recorded during this task and the generators of the N2 subcomponents were identified using standardized weighted low-resolution electromagnetic tomography (swLORETA). RESULTS: PD patients displayed fewer N2 generators than HCs in both the DLPFC and the ACC, for all types of stimuli. In contrast to controls, PD patients did not show any differences between their generators for different N2 subcomponents. CONCLUSION: Our data suggest that impaired inhibition in PD results from dysfunction of the DLPFC and the ACC during the early stages of attentional processes. PMID- 26135908 TI - The effects of study task on prestimulus subsequent memory effects in the hippocampus. AB - Functional magnetic resonance imaging (fMRI) was employed to examine the effects of a study task manipulation on pre-stimulus activity in the hippocampus predictive of later successful recollection. Eighteen young participants were scanned while making either animacy or syllable judgments on visually presented study words. Cues presented before each word denoted which judgment should be made. Following the study phase, a surprise recognition memory test was administered in which each test item had to be endorsed as "Remembered," "Known," or "New." As expected, "deep" animacy judgments led to better memory for study items than did "shallow" syllable judgments. In both study tasks, pre-stimulus subsequent recollection effects were evident in the interval between the cue and the study item in bilateral anterior hippocampus. However, the direction of the effects differed according to the study task: whereas pre-stimulus hippocampal activity on animacy trials was greater for later recollected items than items judged old on the basis of familiarity (replicating prior findings), these effects reversed for syllable trials. We propose that the direction of pre stimulus hippocampal subsequent memory effects depends on whether an optimal pre stimulus task set facilitates study processing that is conducive or unconducive to the formation of contextually rich episodic memories. PMID- 26135909 TI - Drug resistance patterns of Mycobacterium tuberculosis complex and associated factors among retreatment cases around Jimma, Southwest Ethiopia. AB - BACKGROUND: Information on the pattern of drug resistant tuberculosis (TB) among re-treatment cases is crucial to develop appropriate control strategies. Therefore, we conducted this study to assess the drug resistance pattern of M. tuberculosis complex (MTBC) isolates and associated factors among re-treatment cases in Jimma area, Southwest Ethiopia. METHODS: Health facility-based cross sectional study was conducted between March 2012 and April 2013 in Jimma area, Southwest Ethiopia. We included 79 re-treatment cases selected conveniently. Socio demographic and clinical data were collected using structured questionnaire. Sputum sample processing, mycobacterial culture, isolation and drug susceptibility testing (DST) were done at Mycobacteriology Research Centre (MRC) of Jimma University. All data were registered and entered in to SPSS version 20. Crude odds ratio (COR) and adjusted odds ratios (AOR) were calculated. P-values less than 0.05 were considered statistically significant. RESULTS: Seventy-nine re-treatment cases included in the study; 48 (60.8%) were males. Forty-seven (59.5%) study participants were from rural area with the mean age of 31.67 +/- 10.02 SD. DST results were available for 70 MTBC isolates. Majority (58.6% (41/70)) isolates were resistant to at least one of the four first line drugs. The prevalence of multidrug-resistant TB (MDR-TB) was 31.4% (22/70). Place of residence (AOR = 3.44 (95 % CI: 1.12, 10.60), duration of illness (AOR = 3.00 (95 % CI: 1.17, 10.69) and frequency of prior TB therapy (AOR = 2.99, (95 % CI: 1.01, 8.86) were significant factors for any drug resistance. Moreover, history of treatment failure was found to be associated with MDR-TB (AOR = 3.43 (95 % CI: 1.14, 10.28). CONCLUSION: The overall prevalence of MDR-TB among re-treatment cases around Jimma was high. The rate of MDR-TB was higher in patients with the history of anti-TB treatment failure. Timely identification and referral of patients with the history of treatment failure for culture and DST need to be strengthened. PMID- 26135910 TI - Perylenetetracarboxylic anhydride as a precursor of fluorescent carbon nanoonion rings. AB - Thermal annealing at 400 degrees C of perylenetetracarboxylic anhydride in low molecular mass PEG gives rise to the formation of well defined nanoobjects of 2.5 nm height and size distribution from 10 to 65 nm (average 40 nm) after purification of the raw mixture with silicagel chromatography. TEM reveals that the flat nanoobjects are constituted of concentric graphenic rings (0.34 nm interlayer distance). The morphology of the nanoparticles resembles onion rings of nanometric dimensions (nanoonion rings C-NOR). C-NOR particles have an excitation dependent emission with lambdaem from 430 to 570 nm and a maximum emission quantum yield of 0.49. C-NOR particles can be internalized into Hep3B human hepatoma cells as determined by confocal fluorescence microscopy and are remarkably biocompatible affecting slightly cell viability according to the MTT test. PMID- 26135911 TI - Syntheses and Structures of Thiophene-Containing Cycloparaphenylenes and Related Carbon Nanohoops. AB - Thiophene-containing cycloparaphenylenes (CPPs) bearing 8, 10, and 16 aromatic and heteroaromatic units in the macrocyclic ring structures were synthesized. Specifically, two and four thiophene-2,5-diyl units were incorporated into functionalized [6]- and [12]CPP macrocyclic carbon frameworks, respectively. In addition, two 2,2'-bithiophene-5,5'-diyl units were inserted into a functionalized [6]CPP carbon framework. The cyclic and differential pulse voltammetry and the UV-vis and fluorescence spectra of the fully aromatized macrocycles and their precursors exhibited interesting electrochemical and optical properties. PMID- 26135912 TI - Incidence and prevalence of dementia in linked administrative health data in Saskatchewan, Canada: a retrospective cohort study. AB - BACKGROUND: Determining the epidemiology of dementia among the population as a whole in specific jurisdictions - including the long-term care population-is essential to providing appropriate care. The objectives of this study were to use linked administrative databases in the province of Saskatchewan to determine the 12-month incidence and prevalence of dementia for the 2012/13 period (1) among individuals aged 45 and older in the province of Saskatchewan, (2) according to age group and sex, and (3) according to diagnosis code and other case definition criteria. METHODS: We used a population-based retrospective cohort study design and extracted data from 10 provincial health databases linked by a unique health services number. The cohort included individuals 45 years and older at first identification of dementia between April 1, 2001 and March 31, 2013 based on case definitions met within any one of four administrative health databases (Hospital Discharge Abstracts, Physician Service Claims, Prescription Drug, and RAI-MDS, i.e., Long-term Care). RESULTS: A total of 3,270 incident cases of dementia (7.28 per 1,000 PAR) and 13,012 prevalent cases (28.16 per 1,000 PAR) were identified during 2012/13. This study found the incidence rate increased by 2.8 to 5.1 times and the prevalence rate increased by 2.6 to 4.6 times every 10 years after 45 years of age. Overall, the age-standardised incidence rate was significantly lower among females than males (7.04 vs. 7.65 per 1,000 PAR) and the age standardised prevalence rate was significantly higher among females than males (28.92 vs. 26.53 per 1,000 PAR). Over one-quarter (28 %) of all incident cases were admitted to long-term care before a diagnosis was formally recorded in physician or hospital data, and nearly two-thirds of these cases were identified at admission with impairment at the moderate to very severe level or a disease category of Alzheimer's disease/other dementia. CONCLUSIONS: Linking multiple sources of registry data contributes to our understanding of the epidemiology of dementia across multiple segments of the population, inclusive of individuals residing in long-term care. This information is foundational for public awareness and policy recommendations, health promotion and prevention strategies, appropriate health resource planning, and research priorities. PMID- 26135913 TI - How cooks navigate nutrition, hunger and care in public-sector foodservice settings. AB - OBJECTIVE: To examine the perspectives and practices of cooks responsible for carrying out healthy meal programmes in publicly funded foodservice, in order to better understand what they consider to be 'good' food and where nutrition and nutritional standards fit into this conceptualization. DESIGN: A qualitative, exploratory study involving in-depth interviews that were conducted with cooks and their supervisors about their work practices and perspectives on providing healthy food for clients. SETTING: Participants were recruited from child-care, after-school, senior-centre and shelter settings that had participated in healthy menu training in New York City, USA. SUBJECTS: Eighteen cooks and nine supervisors working in the aforementioned settings. RESULTS: The views and practices of both cooks and supervisors about what constitutes 'good' food extend beyond a purely nutritional view of goodness to include the importance of addressing hunger and clients' food preferences, among other factors. Cooks address these by interacting with clients and altering recipes and menus in a range of ways to maximize the likelihood of food consumption and enjoyment. These approaches are often, but not always, compatible with setting-specific nutritional guidelines that may be set at the national, state, local or organizational level. CONCLUSIONS: Cooks play a key role in translating nutritional guidelines into what is served. In doing so, they engage in skilled labour and forms of care that increase the ability of public-sector foodservice to address food security and other goals, but these aspects of their work are not widely recognized. PMID- 26135914 TI - Bioactive C21 Steroidal Glycosides from the Roots of Cynanchum otophyllum That Suppress the Seizure-like Locomotor Activity of Zebrafish Caused by Pentylenetetrazole. AB - Six new C21 steroidal glycosides, cynotophyllosides A-F (1-6), together with 16 known compounds, were isolated from the roots of Cynanchum otophyllum. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The three major components, otophylloside F (15), otophylloside B (17), and rostratamine 3-O-beta-D-oleandropyranosyl-(1->4)-beta-D cymaropyranosyl-(1->4)-beta-D-cymaropyranoside (18), suppressed the seizure-like locomotor activity caused by pentylenetetrazole in zebrafish. Preliminary structure-activity relation studies revealed that a pregnene skeleton with a C-12 ester group (ikemaoyl > cinnamoyl > hydroxy > p-hydroxybenzoyl) and a C-3 sugar chain consisting of three 2,6-dideoxysaccharide units is essential for this suppressive activity. PMID- 26135915 TI - Amelioration of Child Depression Through Behavioral Parent Training: A Preliminary Study. AB - Child depression is an impairing condition for which tested treatments have shown relatively modest mean effects. One possible explanation is that the treatments have generally adopted an individual child focus, without addressing the dysfunctional parent-child interactions that often accompany child depression. The present study provides preliminary evidence bearing on this hypothesis, using data from a treatment outcome study in which clinically referred children with a depression diagnosis could receive individual cognitive behavioral therapy (CBT) focusing on the depression or behavioral parent training (BPT) focusing on comorbid conduct problems. Among children in the study who met criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed.) depressive disorders, we identified two groups, matched on gender and age: 15 who received only CBT focused on child depression and 15 who received only BPT focused on child conduct problems. Children were 7 to 13, 20 of whom were male, and race included Caucasian (17), Latino (5), African American (2), and multirace (6). Measures assessed depressive diagnoses and symptoms, as well as parenting stress. Analyses focused on whether BPT alone might lead to reduced depression, and if so how that reduction would compare to the depression reduction achieved through CBT that focused on depression. Both groups showed significant reductions from pre- to post-treatment in depressive diagnoses and depression symptoms, and there were no BPT versus CBT group differences at post-treatment. BPT that focuses on child conduct problems, with no emphasis on depression treatment, may produce significant depression reduction in comorbid children who meet criteria for depressive disorders. PMID- 26135916 TI - In Situ Photocatalytically Heterostructured ZnO-Ag Nanoparticle Composites as Effective Cathode-Modifying Layers for Air-Processed Polymer Solar Cells. AB - A heterostructured semiconductor-metal ZnO-Ag nanoparticle (NP) composite was constructed through a straightforward photocatalytic strategy by using UV irradiation of ZnO NPs and an aqueous solution of Ag precursor. The ZnO-Ag NP composites serve as an effective cathode-modifying layer in polymer solar cells (PSCs) with increased short-circuit current density owing to the light-trapping effect, and improved optical and electrical conductivity properties compared with pure ZnO NPs. The Ag NPs, which are photodeposited in situ on ZnO NPs, can act as effective antennas for incident light to maximize light harvesting and minimize radiative decay or nonradiative losses, consequently resulting in the enhanced photogeneration of excitons in PSCs. Systematic photoelectron and -physical investigations confirm that heterostructured ZnO-Ag NPs can significantly improve charge separation, transport, and collection, as well as lower charge recombination at the cathode interface, leading to a 14.0 % improvement in air processed device power conversion efficiency. In addition, this processable, cost effective, and scalable approach is compatible with roll-to-roll manufacturing of large-scale PSCs. PMID- 26135917 TI - Spatial oxygenation profiles in tumors during normo- and hyperbaric hyperoxia. AB - BACKGROUND: Inspiratory hyperoxia reduces tumor hypoxia, which is responsible for limited radiosensitivity of tumors. However, very little is known about the heterogeneity of intratumoral oxygenation during this supportive treatment. The study analyzes whether local hypoxia is still present during normobaric and hyperbaric inspiratory hyperoxia and whether the addition of CO2 to the inspiratory gas affects the spatial pO2 distribution. MATERIAL AND METHODS: Tumor oxygenation of experimental DS-sarcomas in rats was assessed by polarographic needle electrodes at 1 and 2 atm (bar) environmental pressure during pure O2 or carbogen (95 % O2 + 5 % CO2) breathing. Up to 320 individual pO2 measurements were performed in a strictly oriented grid resulting in an oxygenation profile in a horizontal tumor layer. RESULTS: In the experimental tumors used the oxygenation showed pronounced heterogeneities with closely adjacent hypoxic and oxygenated regions. This heterogeneity was still visible under normobaric hyperoxia where large confluent hypoxic regions were detectable. At 1 atm, the addition of CO2 improved tumor oxygenation significantly (at least in large tumors). At 2 atm, only very small local regions of hypoxia were detected. However, under this condition hypercapnia had no impact on tumor oxygenation. CONCLUSIONS: The data show that even under hyperbaric hyperoxia, hypoxic regions are detectable despite the average pO2 increased by a factor of 100. The results also clearly indicate that the oxygenation pattern improves disproportionally with increasing environmental pressure. PMID- 26135919 TI - Cloning and extracellular expression of a raw starch digesting alpha-amylase (Blamy-I) and its application in bioethanol production from a non-conventional source of starch. AB - The aim of this study was to clone and efficiently express a raw starch-digesting alpha-amylase enzyme in the culture media and also to investigate the potential application of this recombinant enzyme in the digestion of non-conventional raw starch for bioethanol production. A raw starch digesting alpha-amylase gene isolated from Bacillus licheniformis strain AS08E was cloned and extracellularly expressed in E. coli cells using the native signal peptide. The mature recombinant alpha-amylase (Blamy-I) consisting of 483 amino acid residues was found to be homogenous with a mass of 55.3 kDa (by SDS-PAGE analysis) and a predicted pI of 6.05. Structural and functional analysis of Blamy-I revealed the presence of an extra Ca(2+) -binding region between the A and C domains responsible for higher thermostability of this enzyme. The statistical optimization of E. coli culture conditions resulted in an approximately eightfold increase in extracellular expression of Blamy-I as compared to its production under non-optimized conditions. Blamy-I demonstrated optimum enzyme activity at 80 degrees C and pH 10.0, and efficiently hydrolyzed raw starch isolated from a non-conventional, underutilized jack fruit seeds. Further utilization of this starch for bioethanol production using Blamy-I and Saccharomyces cerevisiae also proved to be highly promising. PMID- 26135918 TI - Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS. AB - Inherited prion disease (IPD) is caused by autosomal-dominant pathogenic mutations in the human prion protein (PrP) gene (PRNP). A proline to leucine substitution at PrP residue 102 (P102L) is classically associated with Gerstmann Straussler-Scheinker (GSS) disease but shows marked clinical and neuropathological variability within kindreds that may be caused by variable propagation of distinct prion strains generated from either PrP 102L or wild type PrP. To-date the transmission properties of prions propagated in P102L patients remain ill-defined. Multiple mouse models of GSS have focused on mutating the corresponding residue of murine PrP (P101L), however murine PrP 101L, a novel PrP primary structure, may not have the repertoire of pathogenic prion conformations necessary to accurately model the human disease. Here we describe the transmission properties of prions generated in human PrP 102L expressing transgenic mice that were generated after primary challenge with ex vivo human GSS P102L or classical CJD prions. We show that distinct strains of prions were generated in these mice dependent upon source of the inoculum (either GSS P102L or CJD brain) and have designated these GSS-102L and CJD-102L prions, respectively. GSS-102L prions have transmission properties distinct from all prion strains seen in sporadic and acquired human prion disease. Significantly, GSS-102L prions appear incapable of transmitting disease to conventional mice expressing wild type mouse PrP, which contrasts strikingly with the reported transmission properties of prions generated in GSS P102L-challenged mice expressing mouse PrP 101L. We conclude that future transgenic modeling of IPDs should focus exclusively on expression of mutant human PrP, as other approaches may generate novel experimental prion strains that are unrelated to human disease. PMID- 26135920 TI - Triple Quenching of a Novel Self-Enhanced Ru(II) Complex by Hemin/G-Quadruplex DNAzymes and Its Potential Application to Quantitative Protein Detection. AB - Herein, a novel "on-off" electrochemiluminescence (ECL) aptasensor for highly sensitive determination of thrombin has been constructed based on the triple quenching of the effect of hemin/G-quadruplex DNAzymes upon the Ru(II) complex based ECL system. First, a strong initial ECL signal was achieved by the dual amplification strategies of (i) intramolecular coreaction of a self-enhanced Ru(II)-based molecule (PTCA-PEI-Ru(II)) and (ii) intermolecular coreaction between PTCA-PEI-Ru(II) and nicotinamide adenine dinucleotide (NADH), which was named the signal-on state. Then, a novel triple quenching of the effect of multifunctional hemin/G-quadruplex DNAzymes upon the Ru(II) complex-based ECL system was designed to realize the desirable signal-off state, which was outlined as follows: (i) the hemin/G-quadruplex DNAzymes mimicked NADH oxidase to oxidize NADH and in situ generate the H2O2, consuming the coreactant of NADH; (ii) its active center of hemin could oxidize the excited state PTCA-PEI-Ru(II)* to PTCA PEI-Ru(III), making the energy and electron transfer quench; (iii) it also acted as horseradish peroxidase (HRP) to catalyze the H2O2 for in situ producing the quencher of O2. Based on triple quenching of the effect of hemin/G-quadruplex DNAzymes, the highly sensitive "on-off" thrombin aptasensor was developed with a wide linear detection range of 1.0 * 10(-14) M to 1.0 * 10(-10) M and a detection limit down to the femtomolar level. PMID- 26135921 TI - Effects of Crude Oil/Dispersant Mixture and Dispersant Components on PPARgamma Activity in Vitro and in Vivo: Identification of Dioctyl Sodium Sulfosuccinate (DOSS; CAS #577-11-7) as a Probable Obesogen. AB - BACKGROUND: The obesity pandemic is associated with multiple major health concerns. In addition to diet and lifestyle, there is increasing evidence that environmental exposures to chemicals known as obesogens also may promote obesity. OBJECTIVES: We investigated the massive environmental contamination resulting from the Deepwater Horizon (DWH) oil spill, including the use of the oil dispersant COREXIT in remediation efforts, to determine whether obesogens were released into the environment during this incident. We also sought to improve the sensitivity of obesogen detection methods in order to guide post-toxicological chemical assessments. METHODS: Peroxisome proliferator-activated receptor gamma (PPARgamma) transactivation assays were used to identify putative obesogens. Solid-phase extraction (SPE) was used to sub-fractionate the water-accommodated fraction generated by mixing COREXIT, cell culture media, and DWH oil (CWAF). Liquid chromatography-mass spectrometry (LC-MS) was used to identify components of fractionated CWAF. PPAR response element (PPRE) activity was measured in PPRE luciferase transgenic mice. Ligand-binding assays were used to quantitate ligand affinity. Murine 3T3-L1 preadipocytes were used to assess adipogenic induction. RESULTS: Serum-free conditions greatly enhanced the sensitivity of PPARgamma transactivation assays. CWAF and COREXIT had significant dose-dependent PPARgamma transactivation activities. From SPE, the 50:50 water:ethanol volume fraction of CWAF contained this activity, and LC-MS indicated that major components of COREXIT contribute to PPARgamma transactivation in the CWAF. Molecular modeling predicted several components of COREXIT might be PPARgamma ligands. We classified dioctyl sodium sulfosuccinate (DOSS), a major component of COREXIT, as a probable obesogen by PPARgamma transactivation assays, PPAR-driven luciferase induction in vivo, PPARgamma binding assays (affinity comparable to pioglitazone and arachidonic acid), and in vitro murine adipocyte differentiation. CONCLUSIONS: We conclude that DOSS is a putative obesogen worthy of further study, including epidemiological and clinical investigations into laxative prescriptions consisting of DOSS. CITATION: Temkin AM, Bowers RR, Magaletta ME, Holshouser S, Maggi A, Ciana P, Guillette LJ, Bowden JA, Kucklick JR, Baatz JE, Spyropoulos DD. 2016. Effects of crude oil/dispersant mixture and dispersant components on PPARgamma activity in vitro and in vivo: identification of dioctyl sodium sulfosuccinate (DOSS; CAS #577-11-7) as a probable obesogen. Environ Health Perspect 124:112-119; http://dx.doi.org/10.1289/ehp.1409672. PMID- 26135922 TI - Automated Analysis of 1p/19q Status by FISH in Oligodendroglial Tumors: Rationale and Proposal of an Algorithm. AB - OBJECTIVE: To propose a new algorithm facilitating automated analysis of 1p and 19q status by FISH technique in oligodendroglial tumors with software packages available in the majority of institutions using this technique. METHODS: We documented all green/red (G/R) probe signal combinations in a retrospective series of 53 oligodendroglial tumors according to literature guidelines (Algorithm 1) and selected only the most significant combinations for a new algorithm (Algorithm 2). This second algorithm was then validated on a prospective internal series of 45 oligodendroglial tumors and on an external series of 36 gliomas. RESULTS: Algorithm 2 utilizes 24 G/R combinations which represent less than 40% of combinations observed with Algorithm 1. The new algorithm excludes some common G/R combinations (1/1, 3/2) and redefines the place of others (defining 1/2 as compatible with normal and 3/3, 4/4 and 5/5 as compatible with imbalanced chromosomal status). The new algorithm uses the combination + ratio method of signal probe analysis to give the best concordance between manual and automated analysis on samples of 100 tumor cells (91% concordance for 1p and 89% concordance for 19q) and full concordance on samples of 200 tumor cells. This highlights the value of automated analysis as a means to identify cases in which a larger number of tumor cells should be studied by manual analysis. Validation of this algorithm on a second series from another institution showed a satisfactory concordance (89%, kappa = 0.8). CONCLUSION: Our algorithm can be easily implemented on all existing FISH analysis software platforms and should facilitate multicentric evaluation and standardization of 1p/19q assessment in gliomas with reduction of the professional and technical time required. PMID- 26135923 TI - Serum Human Chorionic Gonadotropin (beta- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study. AB - OBJECTIVE: To establish clearance curves for serum beta -hCG in women with successfully expectantly managed tubal ectopic pregnancies. DESIGN: Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum beta hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial beta hCG measurements until serum beta hCG was less than 20 IU/l, or the urine pregnancy test was negative. SETTING: Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). PATIENTS: We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. MAIN OUTCOME MEASURE: Serum beta hCG level. RESULTS: Mean initial serum beta- hCG was 488 IU/L (41 - 4883) and median serum beta hCG clearance time was 19 days (5 - 82). The average half-life of beta hCG clearance was 82.5 hours (+/-SD 50.2) in patients with steadily declining serum beta- hCG levels compared to 106.7 hours (+/-SD 72.0) in patients with primarily plateauing beta-hCG levels in the declining phase. However, these differences were not significant (p>0.05). CONCLUSION: We identified a median follow-up of 19 days until serum beta hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum beta hCG showed a longer follow-up time until clearance compared to women with steadily declining beta hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management. PMID- 26135924 TI - Ocular Fluid As a Replacement for Serum in Cell Cryopreservation Media. AB - Cryostorage is of immense interest in biomedical research, especially for stem cell-based therapies and fertility preservation. Several protocols have been developed for efficient cryopreservation of cells and tissues, and a combination of dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS) is commonly used. However, there is a need for an alternative to FBS because of ethical reasons, high cost, and risk of contamination with blood-borne diseases. The objective of the present study was to examine the possibility of using buffalo (Bubalus bubalis) ocular fluid (BuOF) to replace FBS in cryomedia. Frozen-thawed cells, which were cryopreserved in a cryomedia with BuOF, were assessed for viability, early and late apoptosis, and proliferation. Three cell lines (CHO, HEK, and C18 4), mouse embryonic stem (mES) cells, and primary cells, such as mouse embryonic fibroblast (MEF) cells, human peripheral blood mononuclear cells (hPBMCs), and mouse bone marrow cells (mBMCs), were cryopreserved in cryomedia containing 10% DMSO (D10) with 20% FBS (D10S20) or D10 with 20% BuOF (D10O20). For all three cell lines and mES cells cryopreserved in either D10S20 or D10O20, thawed cells showed no difference in cell viability or cell recovery. Western blot analysis of frozen-thawed-cultured cells revealed that the expression of Annexin V and proliferating cell nuclear antigen (PCNA) proteins, and the ratio of BAX/BCL2 proteins were similar in all three cell lines, mES cells, and hPBMCs cryopreserved in D10S20 and D10O20. However, initial cell viability, cell recovery after culture, and PCNA expression were significantly lower in MEF cells, and the BAX/BCL2 protein ratio was elevated in mBMCs cryopreserved in D10O20. Biochemical and proteomic analysis of BuOF showed the presence of several components that may have roles in imparting the cryoprotective property of BuOF. These results encourage further research to develop an efficient serum-free cryomedia for several cell types using BuOF. PMID- 26135925 TI - Functional metabolomics: from biomarker discovery to metabolome reprogramming. AB - Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible for metabolic characteristics and revealing metabolic mechanisms, which construct the content of discovery metabolomics. The crucial biomarkers can be used to reprogram a metabolome, leading to an aimed metabolic strategy to cope with alteration of internal and external environments, naming reprogramming metabolomics here. The striking feature on the similarity of the basic metabolic pathways and components among vastly different species makes the reprogramming metabolomics possible when the engineered metabolites play biological roles in cellular activity as a substrate of enzymes and a regulator to other molecules including proteins. The reprogramming metabolomics approach can be used to clarify metabolic mechanisms of responding to changed internal and external environmental factors and to establish a framework to develop targeted tools for dealing with the changes such as controlling and/or preventing infection with pathogens and enhancing host immunity against pathogens. This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics. PMID- 26135926 TI - Increased p-cresyl sulfate level is independently associated with poor outcomes in patients with heart failure. AB - Amino acid-derived metabolites, including protein-bound uremic toxins, may have prognostic value for patients with heart failure (HF). The aim of this study was to investigate whether p-cresyl sulfate (PCS), indoxyl sulfate (IS), and arginine metabolites provided prognostic values in addition to the traditional biomarker, B-type natriuretic peptide (BNP), in patients with HF. Chromatography mass spectrometry was performed to measure tyrosine, tryptophan, arginine, PCS, IS, and asymmetric (ADMA) and symmetric dimethylarginine (SDMA) in the plasma from 51 normal controls and 136 HF patients. Compared to the normal controls, PCS levels significantly increased in HF patients (p = 0.003). During the follow-up (2.3 +/- 1.1 years), 35 (25.7 %) patients experienced a composite event of death or HF related re-hospitalization. In univariable analysis, PCS, estimated glomerular filtration rate (eGFR), BNP, DMA/arginine ratio, and ADMA/arginine ratio were associated with a higher rate of composite events. In the multivariable analysis, PCS was the only independent predictor of composite events [hazard ratio (HR) 1.06 (per 10 MUM), 95 % confidence interval (CI) 1.01-1.11, p = 0.02]. Kaplan Meier curves showed that a PCS level of >=50 MUM was significantly associated with a higher composite event rate than those with a PCS level of <50 MUM (Log rank = 5.11, p = 0.024; HR 2.13, 95 % CI 1.09-4.16, p = 0.02). In conclusion, among protein-bound uremic toxins, eGFR, and DMA metabolites, increased PCS is the only independent predictor of HF-related events in patients with HF. A combination of PCS and BNP should better risk-stratify patients with HF. PMID- 26135927 TI - Aortic smooth muscle cell alterations in mice systemically exposed to arsenic. AB - Previous epidemiological studies showed that chronic arsenic exposure is related to increased cardiovascular disease incidence. The detailed biochemical mechanisms by which arsenic exerts its effects remain unknown. Vascular disease progression is characterized by smooth muscle cell (SMC) phenotypic switching, vessel wall reorganization, and platelet-derived growth factor (PDGF) production. The objective of this study was to examine early biochemical and structural changes in the aortas of ICR mice systemically exposed to arsenic. Animals were fed sodium arsenite (20 mg/kg) via gavage 5 days/week or Milli-Q water only (control) for 8 weeks. Aortic proteins were subjected to two-dimensional (2-D) differential gel electrophoresis and proteomic studies. Two 2-D gel protein spots were identified as the same protein, smooth muscle (SM)22alpha, using proteomics. SM22alpha and Rho kinase 2 gene and protein expression were significantly decreased in the aortic tissue of arsenic-exposed mice compared with that of control mice. No atherosclerotic lesion formation or tissue injury was detected in the aortic wall of either the arsenic-fed or the control group. However, the percent (%) SMC area of the aortic wall was significantly decreased in arsenic fed mice compared with that in control mice. Additionally, the expression levels of PDGF-BB and early growth response-1 (Egr-1) were significantly higher in the arsenic group than that in the control group. These findings reveal biochemical alterations of SM22alpha, PDGF, and Egr-1 in conjunction with decreased SMC area in the aortic wall of arsenic-fed mice. Arsenic may initiate aortic SMC alterations that subsequently lead to vascular dysfunction. PMID- 26135928 TI - Indications, applications, and outcomes of inferior vena cava filters for venous thromboembolism in Japanese patients. AB - A recent multicenter registry study of venous thromboembolism (VTE) patients in Japan demonstrated a high prevalence of inferior vena cava (IVC) filter placement. However, data regarding indications, applications, and outcomes of IVC filters in Japanese patients are quite limited. This study was an observational, single-center, retrospective cohort study of all consecutive patients with acute VTE treated between March 2006 and February 2014. Data extracted included patient demographics, indications, applications, and complications of IVC filters, as well as VTE recurrence and death. A total of 257 consecutive patients were analyzed. Seventy-eight patients (30 %) received IVC filters. The proportions of IVC filter placement were 26 % for deep-vein thrombosis (DVT) alone, 10 % for pulmonary embolism (PE) alone, and 46 % for both DVT and PE. There was no significant difference in patient demographics between the IVC filter group and no-IVC filter group. Stated indications for filter placement were 24 cases (30 %) of DVT in intrapelvic veins, 16 cases (20 %) of DVT in proximal veins, and 11 cases (14 %) of contraindication to anticoagulant therapy. In the IVC filter group, cases of class I indication (guidelines: JCS 75:1258-1281, 2009) numbered only 6 (8 %). Many of the retrievable IVC filters were not removed and placed permanently and the retrieval rate was 42 %. We found complications of IVC filters in 8 cases (10 %). IVC filter placement was significantly associated with a better survival rate and a higher incidence of DVT recurrence during a mean observation period of 541 days. Our research suggests the frequent use of IVC filters for VTE treatment, combined with a low retrieval rate. Most of the stated indications of IVC filter placement for VTE in Japanese patients were cases of DVT in intrapelvic veins or proximal veins, not cases of contraindication to anticoagulant therapy. PMID- 26135929 TI - A Systematic Review and Meta-Analysis of Three Gene Variants Association with Risk of Prostate Cancer: An Update. AB - PURPOSE: Prostate cancer (PCa) is one of the most commonly diagnosed male malignancies. Nu-merous studies have investigated the role of genetic variants in PCa risk. However, the results re-main unclear. The purpose of this study was to evaluate the relationship between single-nucleo-tide polymorphism (SNP) rs2228001 in xeroderma pigmentosum group C (XPC), SNP rs4073 in interleukin 8 (IL8), and SNP rs2279744 in mouse double minute 2 (MDM2) homolog gene with PCa susceptibility. MATERIALS AND METHODS: Electronic database of PubMed, Medline, and Embase were searched for eligible articles published between January 2000 and April 2014. The odd ra-tio (OR) with its 95% confidence interval (CI) were calculated to estimate the strength of association. RESULTS: A total 18 case control studies, including 5725 PCa cases and 5900 healthy controls, were screened out. Six studies were eligible for each SNP. For XPC 939A/C polymorphism, no significant association was found with PCa risk in the whole population (P > .05). No relationship in subgroup analysis was found by ethnicity. For IL8 -251T/A variant, the A allele was not related with PCa risk in any genetic models when compared with those individuals without A allele. For MDM2 -309T/G mutation, the G allele was not as-sociated with the increased risk of PCa in total population and subgroup analysis by ethnicity as well. CONCLUSION: Our study demonstrated that all these three genetic polymorphisms were not associated with an in-creased risk of developing PCa, which might also provide an insight into the future research. Further large-scale studies with concerning the gene-gene and gene-environment interactions are needed to elucidate final conclusion. PMID- 26135930 TI - Epidemiologic and Clinical Characteristics of Patients Presenting with Renal Colic in Korea. AB - PURPOSE: To investigate the epidemiologic and clinical characteristics of renal colic in Korea. MATERIALS AND METHODS: Forty-six participating emergency departments provide their essential informa-tion to the National Emergency Medical Center. We extracted the National Emergency Department Informa-tion System data from January to December 2010. We analyzed data on demographics, visit time, chief com-plaints, mode of arrival, outcome, and length of stay. A total of 23,653 patients with renal colic visited the 46 emergency departments, and this patient population comprised 1.8% of all emergency department visits. RESULTS: The median patient age was 45 years, and the male-to-female ratio was 2:1. The peak time of inci-dence for patients with renal colic occurred between 06:00 and 10:00 h. The peak incidence occurred in Au-gust, whereas the lowest incidence occurred in winter. The most common chief complaint was flank pain, followed by abdominal pain and hematuria. The median length of stay in the emergency department was 171 min, and female patients stayed longer in the emergency department relative to male patients. The medi-an length of stay was shorter for weekend visits than for weekday visits. Most patients were discharged from the emergency department; only 6% of patients were admitted. Monday was the day with the highest ad-mission rate. The length of stay did not correlate with age, whereas the admission rate increased with age. CONCLUSION: The epidemiologic and clinical features derived from this study may facilitate further investigations aimed at understanding the etiology of renal colic. PMID- 26135931 TI - Laparoscopic Radical Prostatectomy after Previous Transurethral Resection of the Prostate in Clinical T1a and T1b Prostate Cancer: A Matched-Pair Analysis. AB - PURPOSE: To analyze and compare surgical, oncological and functional outcomes of laparoscopic radi-cal prostatectomy (LRP) in patients with and without previous transurethral resection of the prostate (TURP). MATERIALS AND METHODS: In total, 785 men underwent LRP at our institution from January 2002 to December 2012. TURP had been performed previously in 35 of these patients (TURP group). A matched pair analysis iden-tified 35 additional men without previous TURP who exhibited equivalent clinicopathological characteristics to serve as a control group. Perioperative complications and surgical, functional, and oncological outcomes were compared between the two groups. RESULTS: The groups were similar in age, body mass index, serum prostate-specific antigen level, and pre- and post operative Gleason scores. Patients in the TURP group had greater blood loss (231 vs. 139 mL), longer opera-tive times (262 vs. 213 min), a greater probability of transfusion (8.6% vs. 0%), and a higher rate of complications (37.1% vs. 11.4%) compared with the control group. The positive surgical margin rate was higher in the TURP group, but this difference was not statistically significant (P = .179). The continence rates at one year after surgery were similar, but a lower continence rate was identified in the TURP group (42.9% vs. 68.6%) at 3 months. Bio-chemical recurrence developed in 17.1% and 11.4% of the patients in the TURP and control groups, respectively, after a mean follow-up of 57.6 months. CONCLUSION: LRP is feasible but challenging after TURP. LRP entails longer operating times, greater blood loss, higher complication rates and worse short term continence outcomes. However, the radical nature of this cancer surgery is not compromised. PMID- 26135932 TI - A Significant Upregulation of miR-886-5p in High Grade and Invasive Bladder Tumors. AB - PURPOSE: To investigate the expression alteration of miR-886-5p in bladder tumors and evaluating its expression level as a potential biomarker in this type of cancer. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) samples of bladder tumors belonging to 70 patients whom had been referred to the Shahid Labbafi-Nejad medical center were obtained from the archival collection of pathology department. After RNA extraction and cDNA synthesis, expression levels of miR-886-5p were quantified by a real-time reverse transcription polymerase chain reaction (RT-PCR) approach. RESULTS: Our data revealed a significant upregulation (~3 times) of miR-886-5p in high grade bladder tumors, compared to the low grade ones (P < .05). Moreover, its expression level could significantly discriminate noninvasive (Ta, T1) from invasive (T-2T4) tumor stages. CONCLUSION: Our data suggests a potential role for miR-886-5p in progression of bladder cancer. PMID- 26135933 TI - Tissue Chromogranin A Expression during Prostate Cancer Progression: Prediction of Chemosensitivity. AB - PURPOSE: We investigated the clinical significance of chromogranin A (CgA) expression as a neuroendocrine (NE) marker during prostate cancer (PCa) progression, especially as a potential predictor of chemotherapeutic response in castration-resistant PCa (CRPC) patients based on immunohistochemical findings. MATERIALS AND METHODS: Sixteen CRPC patients who underwent combination (docetaxel/estramustine/ carboplatin; DEC) chemotherapy were retrospectively studied. Immunostaining of CgA was performed using prostate biopsy samples obtained at the initial PCa diagnosis, during androgen deprivation therapy, at the time of CRPC diagnosis, and after 2 cycles of DEC therapy. The positive rate was expressed as the mean percentage of positively stained tumor cells against the total number of tumor cells. Differences in positive rates among the treatment courses were compared using a Mann-Whitney test. RESULTS: The mean percentage of CgA-positive PCa cells increased in a stepwise manner until CRPC development and then significantly decreased after DEC therapy. Subanalysis of CgA at CRPC diagnosis showed a more evident reduction of CgA expression after DEC therapy in patients who also had a high level of CgA as compared to those with a low CgA level (P = .003). Likewise, longer prostate-specific antigen progression free survival was related to CRPC and high CgA (P = .028). CONCLUSION: NE differentiation of PCa cells is accelerated despite androgen deprivation and reaches a peak at the time of CRPC diagnosis. Although further studies using larger samples are needed, CgA expression in CRPC may be a candidate tissue biomarker to reflect the chemotherapy sensitivity of individual PCa cells. PMID- 26135934 TI - Investigation of Renal Cell Carcinoma by Contrast-Enhanced Ultrasound- Predictive Value of Time Intensity Curve Analysis in Establishing Local Tumor Invasion and Stage: A Pilot Study. AB - PURPOSE: Contrast-enhanced ultrasound (CEUS) allows for real-time examination of signal intensity changes in a region of interest (ROI) and quantification of contrast agent kinetics. This study assessed the predictive ability of time intensity curve (TIC) parameters for local tumor invasion and T stage of renal cell carcinoma (RCC). MATERIALS AND METHODS: Renal tumors in 41 patients were examined by CEUS. Thirty-two met the inclusion criteria, with a total of 33 tumors (27 clear cell, 4 chromophobe, and 2 papillary type I). Nineteen (57.6%) tumors were included in group A (stages pT1 and pT2) and 14 (42.4%) in group B (stage pT3). ROIs were established as: whole tumor (TuW); tumor area with the highest signal intensity (TuMAX) and renal cortex (Ref). The TIC param-eters for each ROI were calculated as below: peak signal intensity, time to peak (TTP), rise time (RT), and mean transit time (MTT). They were analyzed as a whole value for each ROI and as a ratio between the different ROIs. RESULTS: There were significant differences between the tumors invading and not invading the renal sinus fat for TTP (TuW/Ref) [0.98 (0.67-1.25) vs. 1.18 (1.08-1.3), P < .05]. For differentiation between groups A and B, the following ratios were proven as predictors by univariate regression analysis: TTP (TuMAX/TuW); MTT (Tu-MAX/TuW); RT (TuMAX/TuW) (P = .03, P = .01 and P = .02, respectively). The value derived from the Receiver Operating Characteristic (ROC) curve for RT (TuMAX/TuW) was 0.8 with sensitivity = 78.6%, specificity = 89.5%, and cutoff value of > 0.91. CONCLUSION: TIC parameters were predictors of locally noninvasive and invasive RCC. PMID- 26135935 TI - Association of Serum Fetuin-A Levels with Allograft Outcome in Renal Transplant Recipients. AB - PURPOSE: To determine serum fetuin-A pattern after renal transplantation and its association with graft outcome. MATERIALS AND METHODS: In 41 renal transplant recipients, serum pretransplant fetuin-A levels and serum fetuin-A concentrations on days 7 and 30 after transplantation were measured using the enzyme-linked immunosorbent as-say (ELISA) method. Also, the association between serum fetuin-A levels with clinical and laboratory parameters was evaluated. RESULTS: A significant decrease in serum fetuin-A levels was noted in the first week after transplantation (P < .001). Subsequently, it started to increase and surpass pretransplant values during the first month (P < .001). Pretransplant fetuin-A levels did not differ among patients with different diethylenetriamine pentaacetic acid (DTPA) results. In addition, serum fetuin-A levels did not significantly correlate with metabolic parameters. CONCLUSION: In this prospective study there was no increase in serum fetuin-A levels during the first month and pretransplant fetuin-A levels are not predictive for allograft outcome in renal transplant recipients. PMID- 26135936 TI - Risk Factors for Women to Have Urodynamic Stress Urinary Incontinence at A Turkish Tertiary Referral Center: A Multivariate Analysis Study. AB - PURPOSE: To investigate the risk factors in women with urodynamic stress urinary incontinence (USTIC) at a Turkish tertiary referral center. MATERIALS AND METHODS: The urodynamic records of 3038 consecutive women were analyzed between 1990 and 2011. The patients who had etiological factor of neurologic disease were excluded. There were 1187 women who had USTIC after urodynamic investigation and 274 women who had no incontinence symptoms were included in the study. Multivariate analyses were done using logistic regression test to determine the risk factors for USTIC. RESULTS: The mean age was 50.1 years (range, 86-18). Increased age, vaginal delivery, cesarean section, anterior prolapse existence in physical examination, previous anti-incontinence surgery, and previous pelvic organ prolapse surgery was found to be significant risk factors for USTIC at multivariate analyses. CONCLUSION: There are risk factors for women to have USTIC. Increased age, having vaginal delivery, having cesarean section, anterior prolapse, previous anti-incontinence surgery and previous prolapse surgery were found to be risk factors for women to have USTIC at this study. PMID- 26135937 TI - Treatment of Recurrent Bacterial Cystitis by Intravesical Instillations of Hyaluronic Acid. AB - PURPOSE: To evaluate the results of intravesical instillations of hyaluronic acid (HA) in the treatment of recurrent bacterial cystitis (RBC), and to assess the rate of tolerability, the rate of recurrence of RBC and side effects of treatment. MATERIALS AND METHODS: The study included 23 female patients from September 2012 to May 2013, aged 28-42 years. Twenty three women with a history of RBC, received intravesical instillations of HA once weekly for 6 weeks then once monthly for 8 months. RESULTS: In 16 (69.6%) of patients, symptoms of RBC resolved after 8 months. In 5 (21.7%) patients after 8 months of HA treatment, urgency was reduced only by 30%. Therefore, it was decided to use combined therapy of HA and alpha blockers in this cohort group. There was a specific reduction (75%) in frequent urination at day and at night without urgency. Despite the use of above mentioned treatment, in 2 (8.7%) patients, RBC was still present and therefore the treatment was discontinued. CONCLUSION: The use of HA protects mucosa of urinary bladder and alleviates symptoms of infection. The intra-vesical instillations of HA and combination of HA + alpha blockers seems to be an effective therapeutic alternative in patients with RBC. PMID- 26135938 TI - Impact of Voiding and Incontinence Symptoms on Health-Related Life Quality in Serbian Male Population. AB - PURPOSE: To investigate the impact of lower urinary tract symptoms on health related quality of life (QoL) in Serbian population considering socio-demographic characteristics, habits, and health status. MATERIALS AND METHODS: The study was conducted in the Primary Healthcare Center "Novi Beograd", Serbia. The study included 1424 male participants, aged 40 years and above. QoL was assessed by using the -36Item Short Form Health Survey (SF36-) questionnaire, while voiding and incontinence symptoms were measured using the International Continence Society Male Short Form (ICS male SF) questionnaire. RESULTS: Voiding and incontinence symptoms significantly correlate with all domains of QoL. Voiding and incontinence symptoms have a high influence on general health, social functioning, physical functioning and body pain. After adjusting for age and education, voiding and incontinence symptoms had a similar influence on QoL. In the multivariate model the influence of cardiovascular diseases and income on QoL was lower than voiding and incontinence symptoms.. CONCLUSION: Voiding and incontinence symptoms affect QoL domains differently. Incontinence symptoms have a greater impact on QoL than voiding symptoms. PMID- 26135939 TI - Obstructive Azoospermia Secondary to Obstructed Ejaculatory Ducts Treated with Resection of the Verumontanum. PMID- 26135940 TI - Solvent Effects on the Encapsulation of Divalent Ions by Benzo-18-Crown-6 and Benzo-15-Crown-5. AB - We measure UV photodissociation (UVPD) spectra of cold benzo-15-crown-5 (B15C5) and benzo-18-crown-6 (B18C6) complexes with divalent ions (M(2+) = Ca(2+), Sr(2+), Ba(2+), and Mn(2+)), solvated with an H2O or a CH3OH molecule: M(2+).B15C5.H2O, M(2+).B15C5.CH3OH, M(2+).B18C6.H2O, and M(2+).B18C6.CH3OH. All the species show a number of sharp vibronic bands in the 36,600-37,600 cm(-1) region, which can be attributed to electronic transitions of the B18C6 or B15C5 component. Conformer-specific IR spectra of these complexes are also obtained by IR-UV double-resonance spectroscopy in the OH stretching region. All the IR-UV spectra of the H2O complexes show IR bands at ~3610 and ~3690 cm(-1); these bands can be assigned to the symmetric and asymmetric OH stretching vibrations of the H2O component. The CH3OH complexes also show the stretching vibration of the OH group at ~3630 cm(-1). The H2O and the CH3OH components are directly bonded to the M(2+) ion through the M(2+)...O bond in all the complexes, but a small difference in the conformation results in a noticeable difference in the OH stretching frequency, which enables us to determine the number of conformers. For Ca(2+), Sr(2+), and Mn(2+), the number of conformers for the B18C6 complexes is in the range of 2-5, which is clearly larger than complexes with B15C5 (1 or 2). However, for Ba(2+) the number of conformers with B18C6 (1 or 2) is almost the same as that with B15C5. This is probably because the Ba(2+) ion is too large to be located in the cavity center of either B15C5 and B18C6, which provides an open site at the Ba(2+) ion suitable for solvation with H2O or CH3OH. The more conformations a complex can take, the more entropically favored it is at nonzero temperatures. Hence, the larger number of conformations suggests higher stability of the complexes under solvated conditions, leading to a higher degree of ion encapsulation in solution. PMID- 26135941 TI - Contagion in Mass Killings and School Shootings. AB - BACKGROUND: Several past studies have found that media reports of suicides and homicides appear to subsequently increase the incidence of similar events in the community, apparently due to the coverage planting the seeds of ideation in at risk individuals to commit similar acts. METHODS: Here we explore whether or not contagion is evident in more high-profile incidents, such as school shootings and mass killings (incidents with four or more people killed). We fit a contagion model to recent data sets related to such incidents in the US, with terms that take into account the fact that a school shooting or mass murder may temporarily increase the probability of a similar event in the immediate future, by assuming an exponential decay in contagiousness after an event. CONCLUSIONS: We find significant evidence that mass killings involving firearms are incented by similar events in the immediate past. On average, this temporary increase in probability lasts 13 days, and each incident incites at least 0.30 new incidents (p = 0.0015). We also find significant evidence of contagion in school shootings, for which an incident is contagious for an average of 13 days, and incites an average of at least 0.22 new incidents (p = 0.0001). All p-values are assessed based on a likelihood ratio test comparing the likelihood of a contagion model to that of a null model with no contagion. On average, mass killings involving firearms occur approximately every two weeks in the US, while school shootings occur on average monthly. We find that state prevalence of firearm ownership is significantly associated with the state incidence of mass killings with firearms, school shootings, and mass shootings. PMID- 26135942 TI - The tumor-suppressive role of BATF2 in esophageal squamous cell carcinoma. AB - BATF2 has been found to be decreased in a variety of human malignancies, while its clinical significance and functional roles in esophageal squamous cell carcinoma (ESCC) remain unknown. Herein, the aim of this study was to investigate the expression pattern and to explore the potential functions of BATF2 in ESCC tissues and cell lines. BATF2 mRNA and protein expression levels in human tissues and human ESCC cell lines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB) and immunohistochemical (IHC) analyses. BATF2 was upregulated by transfection of the pcDNA3.1-BATF2 plasmid into KYSE-410 cells. MTT and Transwell assays were used to investigate the effects of BATF2 on cellular proliferation and invasion. Survival curves were plotted using Kaplan-Meier plots and log-rank tests. Cox's proportional hazards regression model was used to analyze univariate and multivariate survival. The results showed that, compared to the matched non-tumor tissues from 36 ESCC patients, 80.56% (29/36) of the tumor tissues presented downregulation of BATF2 by WB analysis (P<0.001). The results of IHC in 104 patients who underwent surgery for ESCC showed that the expression of BATF2 was closely related to tumor differentiation (P=0.023) and lymph node metastasis (P=0.027), while there was no significant correlation with age (P=0.574), gender (P=0.357), tumor location (P=0.721) and TNM stage (P=0.126) of the patients. Pathological grade (P=0.027), clinical stage (P=0.000), lymph node metastasis (P=0.002) and BATF2 expression (P=0.028) were identified as independent prognostic factors for overall survival (OS). In the in vitro studies, upregulation of BATF2 expression significantly inhibited the proliferation and invasive ability of the human ESCC KYSE-410 cells. In conclusion, as a tumor suppressor, BATF2 serves as a prognostic biomarker of ESCC and it may be a potential therapeutic target for ESCC treatment. PMID- 26135943 TI - Identification of the Chemical Bonding Prompting Adhesion of a-C:H Thin Films on Ferrous Alloy Intermediated by a SiCx:H Buffer Layer. AB - Amorphous carbon (a-C) and several related materials (DLCs) may have ultralow friction coefficients that can be used for saving-energy applications. However, poor chemical bonding of a-C/DLC films on metallic alloys is expected, due to the stability of carbon-carbon bonds. Silicon-based intermediate layers are employed to enhance the adherence of a-C:H films on ferrous alloys, although the role of such buffer layers is not yet fully understood in chemical terms. The chemical bonding of a-C:H thin films on ferrous alloy intermediated by a nanometric SiCx:H buffer layer was analyzed by X-ray photoelectron spectroscopy (XPS). The chemical profile was inspected by glow discharge optical emission spectroscopy (GDOES), and the chemical structure was evaluated by Raman and Fourier transform infrared spectroscopy techniques. The nature of adhesion is discussed by analyzing the chemical bonding at the interfaces of the a-C:H/SiCx:H/ferrous alloy sandwich structure. The adhesion phenomenon is ascribed to specifically chemical bonding character at the buffer layer. Whereas carbon-carbon (C-C) and carbon-silicon (C Si) bonds are formed at the outermost interface, the innermost interface is constituted mainly by silicon-iron (Si-Fe) bonds. The oxygen presence degrades the adhesion up to totally delaminate the a-C:H thin films. The SiCx:H deposition temperature determines the type of chemical bonding and the amount of oxygen contained in the buffer layer. PMID- 26135944 TI - Alcohol-induced hypertension: an important healthcare target in Belgium. AB - Excessive alcohol intake is one of the leading causes of premature death in Europe and particularly in Belgium. Belgian people are consuming more alcohol per year than the European average. It is well established that excessive alcohol consumption is a significant predictor of the development of hypertension (HTN). Two million adults in Belgium suffer from HTN and this number will increase to three million by 2025. Less than 50% of Belgian people treated for HTN are well controlled. Alcohol reduction in patients with HTN can significantly lower systolic and diastolic blood pressure. After reviewing the epidemiology of HTN and alcohol disorders in Belgium, this paper will focus on the rationale for alcohol screening and brief intervention in primary care. It will also describe the barriers to alcohol screening, and what could be the benefits of alcohol screening for our healthcare system. The authors believe that early identification through alcohol screening and brief intervention in general practice can help to improve the management of patients with HTN, to reach the targets of the WHO Global Action Plan, i.e., a 25% relative reduction in the risk of premature mortality from cardiovascular diseases, cancer, diabetes or chronic respiratory diseases. They are also convinced that this would allow achieving major healthcare savings. PMID- 26135945 TI - Corrigendum: Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency. PMID- 26135946 TI - Cortisol and testosterone increase financial risk taking and may destabilize markets. AB - It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders' financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways. PMID- 26135948 TI - Delivery room management of ELBW infants in Italy. AB - In this article we evaluated the consistency of practice and the adherence to the International Guidelines in early delivery room management of ELBW infants in Italy. A polyethylene bag/wrap was used by 54 centres (55.1%). In Northern regions, one centre (2.5%) reported to use oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was widely used (77/97, 79.4%). A median of 13% (IQR: 5% 30%) of ELBW infants received chest compressions at birth in Italy. Forty-seven out of 98 (47.9%) centres declared to administer prophylactic surfactant in delivery room. Although there were geographic differences in the country, our results showed a good general adherence to the International Guidelines for Neonatal Resuscitation. PMID- 26135949 TI - Respiratory management of ELGA infants in a region of Southern Italy. AB - The distribution of births in many regions of Southern Italy is scattered among a high number of level I centers, many of which still count less than 500 deliveries per year. Campania, the region around Naples, is no exception and this excessive fragmentation results in a high number of neonatal transports, many of which for respiratory distress. In the present paper, we review three different regional peculiarities relevant to the respiratory management of extremely low gestational age babies. PMID- 26135947 TI - Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling. AB - OBJECTIVES: Obesity and diabetes are well-known risk factors for the development of endometrial cancer. A high rate of aerobic glycolysis represents a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. This study aimed to investigate the effect of various concentrations of glucose on cell proliferation in endometrial cancer. METHODS: ECC-1 and Ishikawa cells were treated with low glucose (1mM), normal glucose (5mM) and high glucose (25mM), and cytotoxicity, apoptosis, cell cycle, adhesion/invasion, and changes of AMPK/mTOR/S6 and MAPK pathways were evaluated. RESULTS: Our results revealed that high glucose increased cell growth and clonogenicity in two endometrial cancer cell lines in a dose dependent manner. Low glucose induced the activity of cleaved caspase 3 and caused cell cycle G1 arrest. High glucose increased the ability of adhesion and invasion by decreasing E-cadherin and increasing Snail expression. In addition, high glucose increased glucose uptake and glycolytic activity through modulating the AMPK/mTOR/S6 and MAPK pathways. CONCLUSIONS: Our findings suggest that glucose stimulated cell proliferation through multiple complex signaling pathways. Targeting glucose metabolism may be a promising therapeutic strategy in the treatment of endometrial cancer. PMID- 26135950 TI - German experience in the management of ELGAN infants. AB - Of 680 000 infants born in Germany a year roughly 10% are preterm and 1% are very preterm. They are treated in around 150 level 1 perinatal centers and there are various credos how to best treat the ELGAN infant. However, many centers include the use of a sustained inflation for lung aeration in the standard protocol of delivery room care in Germany. As a result of the large studies on delivery room care, a trend for earlier or prophylactic surfactant in the most immature infants can be observed, however, surfactant is increasingly given in a new less invasive way called LISA. German randomized controlled trials on LISA , on permissive hypercapnia in the premature infants and a German initiated European trial on inhaled steroids have been completed and preliminary results are available. NIRS so far mostly is used for research reasons; however, the number of centers that monitor brain oxygenation for clinical reasons to guide hemodynamic management is increasing. A recent initiative was able to tremendously reduce the rate of IVH by prospective multidisciplinary surveillance. PMID- 26135951 TI - Obstetrical management of fetus with intra uterine growth restriction (IUGR) and late IUGR. AB - In this article we evaluated an important complication of pregnancy, the fetal growth restriction (IUGR). IUGR is defined as an estimated fetal weight of fetal abdominal circumference below the 10th centile measured by ultrasound according to local standards. We present the prenatal surveillance, the screening tests for late IUGR and the new diagnostic examinations, to establish the best prevention system for IUGR and late IUGR. PMID- 26135952 TI - LISA: Surfactant administration in spontaneous breathing. Which evidence from the literature? AB - Recent human and animal studies demonstrated that surfactant can be delivered intratracheally without traditional intubation and bagging, but using a fine catheter inserted into the trachea of spontaneously breathing preterm infants on CPAP. This strategy, known as LISA (less invasive surfactant administration) or MIST (minimal invasive surfactant therapy), seems to reduce failure of non invasive respiratory approach. Avoiding mechanical ventilation and manual inflation it is possible to reduce lung injury due to baro-volutrauma. Moreover leaving the infants supported by N-CPAP during the maneuver, it is possible to reduce the risk of lung derecruitment. Further studies are needed to confirm the promising effects due to this strategy to deliver surfactant. PMID- 26135953 TI - Hemodynamic management of the preterm infant with acute respiratory failure: role of the functional echocardiography. AB - The functional echocardiography is a useful tool to evaluate the hemodynamic status of preterm infants, often needing a respiratory support during the first critical days of life. In NICU it can be helpful either for the clinical monitoring or the therapeutic management and the use of this technique can potentially improve short-term outcome of preterm infants. PMID- 26135954 TI - Caffeine for preterm infants: current indications and uncertainties. AB - Caffeine is one of the most commonly used therapies in Neonatology, with different indications such as the treatment of apnea and the prevention of extubation failure and bronchopulmonary dysplasia. However, there are still uncertainties regarding effects on central nervous system development, time of discontinuation and dosing of the drug. PMID- 26135955 TI - Late preterm babies and the risk of neurological damage. AB - Late preterm infants (born between 34+0 and 36+6 weeks gestation) account for the recent striking increase in premature birth and they carry a higher vulnerability to suffer brain insults compared to term infants. These babies can develop any kind of known brain lesions including those affecting the most premature babies (i.e.an intraventricular haemorrhage) and lesions affecting more typically term babies like asphyxia and stroke. In other words there is not a specific brain lesion characterizing this gestational age group, and there is not a specific maturational landmark although "subplate neurons" are suppose to ultimate their connectivity in this period and the cortical volume is significantly increasing. In addition we should not forget the possibility that "late preterm babies" may present neurological clinical impairments in the absence of recognized morphological brain lesions even with the use of highly sophisticated MR imaging techniques. For these reasons a wider use of more sophisticated neuro radiological studies is not sufficient to better understand why some studies highlight that the risk of developmental delay or disability can reach 36% higher among late preterm infants compared with term infants. We believe we should improve also our skills to identify even those very subtle clinical signs of impairment deserving further investigations although we often admit these babies in the normal post natal nurseries where clinical observation cannot be so appropriate. PMID- 26135957 TI - A randomized controlled trial of a multi-dose bystander intervention program using peer education theater. AB - This article reports findings from a longitudinal, experimental evaluation of a peer education theater program, Students Challenging Realities and Educating Against Myths (SCREAM) Theater. This study examines the impact of SCREAM Theater on a range of bystander-related outcomes (i.e. bystander intentions, bystander efficacy, perception of friend norms and bystander behaviors) in situations involving sexual violence and whether there was a differential impact of the program by participant sex. First-year college students completed three waves of surveys (pretest, first post-test and second post-test). All participants received one dose of the intervention during summer orientation after the pretest. After the first post-test, participants were randomly assigned to receive two additional doses, or to a control condition, in which they received no additional doses. Students in both one- and three-dose groups reported a number of positive increases. Overall, an intent-to-treat analysis (n = 1390) indicated three doses of the intervention during the first semester of college resulted in better outcomes than the one-time intervention during summer orientation alone. Although both male and female students' scores increased during the study period, female students consistently scored higher than male students on each outcome. The findings suggest that peer education theater holds promise for bystander intervention education on college campuses. PMID- 26135958 TI - Roles of A20 in autoimmune diseases. AB - A20 (TNFAIP3), known to inhibit NF-kappaB function by deubiquitinating-specific NF-kappaB signaling molecules, has been found in many cell types of the immune system. Recent findings suggest that A20 is essential for the development and functional performance of dendritic cell, B cell, T cell and macrophage. A number of studies further demonstrate that these cells are crucial in the pathogenesis of autoimmune diseases, such as type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease, ankylosing arthritis, Sjogren's syndrome and rheumatoid arthritis. In this article, we focus on the recent advances on the roles of A20 in autoimmune diseases and discuss the therapeutic significance of these new findings. PMID- 26135959 TI - MicroRNA-7 inhibits the malignant phenotypes of non-small cell lung cancer in vitro by targeting Pax6. AB - MicroRNA (miR)-7 has been reported to act as a suppressor in several types of cancer, including non-small cell lung cancer (NSCLC). In addition, paired box 6 (Pax6), a highly conserved transcriptional factor, has been implicated in NSCLC. However, the exact role of miR-7, and the association between miR-7 and Pax6 in NSCLC cells remain to be fully elucidated. The present study demonstrated that miR-7 was downregulated and Pax6 was upregulated in NSCLC cell lines. Subsequently, it was demonstrated that overexpression of miR-7 notably inhibited the protein expression of Pax6, while inhibition of miR-7 enhanced the protein expression of Pax6 in NSCLC A549 cells. Further investigation identified Pax6 as a target of miR-7 in A549 NSCLC cells. Ina ddition, the overexpression of miR-7 significantly inhibited A549 cell proliferation and invasion, which was reversed by upregulation of Pax6. Investigation of the underlying molecular mechanism revealed that the extracellular signal-regulated kinase (ERK) and p38 mitogen activated protein kinase (MAPK) signaling pathways were downregulated in the miR 7-overexpressed A549 cells, but were activated in the Pax6-overexpressed A549 cells. Based on these findings, it was suggested that miR-7 negatively regulates the protein level of Pax6, which can promote the proliferation and invasion of NSCLC cells via activation of the ERK and MAPK signaling pathways. Therefore, miR 7/Pax6 may offer potential for use as a target for the treatment of NSCLC. PMID- 26135960 TI - THYROID NODULES WITH 2 PRIOR INADEQUATE FINE-NEEDLE ASPIRATION RESULTS: EFFECT OF INCREASING THE DIAMETER OF THE NEEDLE. AB - OBJECTIVE: The major limitation of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) procedures of thyroid nodules are the cytologically nondiagnostic results. The role of increasing the diameter of the needle in the third FNAB (FNAB#3) due to inadequate cytology has as yet not been investigated. The aim of the present study was to evaluate whether increasing the needle diameter could improve the cytologic sampling of thyroid nodules following 2 previous nondiagnostic US-FNAB results. METHODS: Between July 2012 and December 2012, 140 consecutive patients with 2 prior nondiagnostic US-FNAB results were enrolled in this prospective investigation. Group 22G consisted of 70 patients (78.5% women; mean age, 52 years) having nodules examined with a 22-gauge (G) needle. Group 27G consisted of 70 patients (75.7% women; mean age, 53 years) having nodules examined with a 27-G needle. RESULTS: The rate of nondiagnostic FNAB results was 42.8% (30 of 70) in group 22G and 64.3% (45 of 70) in group 27G, which was a significant difference (P = .011). The large-bore (22 G) needle was found to be statistically significantly superior compared with the small-bore (27 G) needle in diagnostic ability for predominantly solid (P = .014), irregular (P = .013), and halo-free (P = .021) nodules. The accuracy rate was 64.6 and 38% for large-bore (22 G) and small-bore (27 G) needles, respectively. CONCLUSION: The results of our study showed that increasing the needle lumen diameter significantly improves diagnostic performance in terms of adequate aspirated material and diagnostic accuracy rate following 2 prior nondiagnostic US-FNABs. PMID- 26135961 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: MANAGEMENT OF ACROMEGALY PATIENTS: WHAT IS THE ROLE OF PRE-OPERATIVE MEDICAL THERAPY? AB - OBJECTIVE: Acromegaly is a complex disease characterized by growth hormone (GH) excess originating in most cases from a pituitary tumor. The goals of treatment include removing the tumor or reducing tumor burden, normalizing GH secretion and insulin-like growth factor 1 levels, and preserving normal pituitary function if possible. Surgery by an experienced neurosurgeon is still considered first-line therapy, especially in cases with small tumors. In the last few decades, significant progress in the development of selective pharmacologic agents has greatly facilitated the management of active acromegaly, with agents such as somatostatin-receptor ligands (SRLs), GH-receptor antagonists, and dopamine agonists. In addition to adjuvant treatment, pre-operative medical therapy and primary therapy in de novo patients are increasingly employed. METHODS: A United States National Library of Medicine PubMed search (through July 2014) was conducted for the following terms: acromegaly, pre-operative medical therapy, somatostatin-receptor ligands, and somatostatin analogs. Articles not in English and those not in peer-reviewed journals were excluded. In reviewing pertinent articles, focus was placed on biochemical and other postoperative outcomes of medical therapy. RESULTS: An analysis of the full effect of pre-operative use of SRLs on surgical outcomes (remission rates and peri-operative complications) is limited by heterogeneity of methodology, low overall surgical cure rates, and different study designs. The assumption that SRL use prior to surgery reduces peri-operative surgical risk has yet to be proven. A variable degree of tumor shrinkage with preoperative SRLs is observed. Likewise, SRL treatment 3 months before surgery may improve surgical remission rates in the short term; however, positive results do not persist in the long term. CONCLUSION: We consider that medical therapy before surgery could play a role in carefully selected patients, but treatment should be individualized. Primary medical therapy with a SRL may be considered in patients with macroadenomas without local mass effects on the optic chiasm, as SRLs have been shown to reduce tumor size and control GH hypersecretion. However, the data are insufficient to support general use of a SRL prior to surgery in order to improve post-surgery biochemical outcomes. Theoretically, patients with severe cardiac and respiratory complications due to acromegaly could potentially benefit from pre-operative SRLs in order to reduce peri-operative morbidity. Further investigation and investment in large randomized long-term clinical trials are needed to define the precise role and duration of pre-surgical medical treatment in acromegaly patients. PMID- 26135962 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: POSTOPERATIVE HYPOPARATHYROIDISM- DEFINITIONS AND MANAGEMENT. PMID- 26135964 TI - A ROLE FOR TRANSPLANT ENDOCRINOLOGISTS--IT'S ABOUT TIME. PMID- 26135963 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: THE INCREASING INCIDENCE OF THYROID CANCER. AB - OBJECTIVE: (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action. METHODS: Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English language articles through December 31, 2013. RESULTS: The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease. CONCLUSION: Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers. PMID- 26135965 TI - COMMENTARY ON THE ROLE OF INSULIN SENSITIZERS ON CARDIOVASCULAR RISK FACTORS IN POLYCYSTIC OVARIAN SYNDROME: A META-ANALYSIS. PMID- 26135966 TI - Recent Reversal of the Upper-Tropospheric Temperature Trend and its Role in Intensifying the East Asian Summer Monsoon. AB - At the beginning of the 21st century, the July and August (JA) mean upper tropospheric temperature over East Asia shows a significant increasing trend, contrary to the decreasing trend in the late 1970 s. The largest warming center is over northern China (between 30 degrees N-45 degrees N and 85 degrees E-120 degrees E) around 300 hPa. Together with the temperature rising, the geo potential height rises above the warming center and drops below, which connects closely to a correspondingly significant decadal shift of the general circulation over East Asia. In the upper-level of the troposphere, an anomalous anti-cyclone dominates, and the 200-hPa westerly jet strengthens due to the increasing pole ward geo-potential height gradient. In the lower-troposphere, the anomalous southerly wind increases around Yangtze River Valley and the East Asian summer monsoon intensifies. The integrated circulation changes seriously impact summer precipitation over East Asia. The so-called "southern flood and northern drought" (SFND) pattern since the 1970 s over eastern China has changed. As the cooling center in the 1970 s moves southward, the dry belt moves southward as well. A wet belt dominates the Huaihe River Valley after the temperature trend reversal at 2005 while southern China experiences a dry condition. PMID- 26135967 TI - MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues. AB - Non-coding microRNAs (miRNAs), involved in post-transcriptional control, are widely involved in the mechanism of cellular resistance to antitumor chemotherapy. Ectopic expression of one of these miRNAs, miRNA-215 (miR-215), leads to chemoresistance by directly targeting dihydrofolate reductase (DHFR) and thymidylate synthase (TS), which are two of the most important targets of chemotherapeutic agents. This indicates the possible upregulation of endogenous miR-215 in the process of chemoresistance by interfering with important transcripts. In the present study, the upregulation of miR-215 was examined in hepatocellular carcinoma (HCC) subcell lines, Adriamycin (ADM)-resistant HepG2 (HepG2/AR), Hep3B (Hep3B/AR) cell lines, and in ADM-treated patients with HCC. Upregulated miR-215 directly targeted DHFR and TS mRNA and reduced their protein expression levels, without altering mRNA levels. The ectopic expression of miR 215 anti-sense oligo-nucleotides in HepG2/AR and Hep3B/AR cells enhanced chemosensitivity, whereas the expression of the miR-215 mimics led to chemoresistance. Notably, the upregulation of miR-215 indirectly increased the protein levels of P53 and P21 levels in the HepG2 cells, which contain functional P53, which is expected to result in the inhibition of proliferation and colony formation. Taken together, the present study demonstrated that the upregulation of miR-215 resulting from ADM treatment in HCC cells leads to the development of insensitivity to ADM and worsens the prognosis of patients with HCC exhibiting mutated P53. PMID- 26135968 TI - Collective optical Kerr effect exhibited by an integrated configuration of silicon quantum dots and gold nanoparticles embedded in ion-implanted silica. AB - The study of the third-order optical nonlinear response exhibited by a composite containing gold nanoparticles and silicon quantum dots nucleated by ion implantation in a high-purity silica matrix is presented. The nanocomposites were explored as an integrated configuration containing two different ion-implanted distributions. The time-resolved optical Kerr gate and z-scan techniques were conducted using 80 fs pulses at a 825 nm wavelength; while the nanosecond response was investigated by a vectorial two-wave mixing method at 532 nm with 1 ns pulses. An ultrafast purely electronic nonlinearity was associated to the optical Kerr effect for the femtosecond experiments, while a thermal effect was identified as the main mechanism responsible for the nonlinear optical refraction induced by nanosecond pulses. Comparative experimental tests for examining the contribution of the Au and Si distributions to the total third-order optical response were carried out. We consider that the additional defects generated by consecutive ion irradiations in the preparation of ion-implanted samples do not notably modify the off-resonance electronic optical nonlinearities; but they do result in an important change for near-resonant nanosecond third-order optical phenomena exhibited by the closely spaced nanoparticle distributions. PMID- 26135969 TI - Correlation between vascular endothelial growth factor and subclinical atherosclerosis in patients with psoriasis. AB - BACKGROUND: Psoriasis is associated with increased risk of atherosclerotic disorders. Vascular endothelial growth factor (VEGF) is an angiogenic factor that was overexpressed in both psoriatic and atherosclerotic lesions. In a prospective controlled study, we investigated the correlation between serum levels of VEGF and subclinical atherosclerosis in patients with moderate to severe psoriasis. METHOD: Sixty patients with moderate to severe psoriasis and 60 age- and gender matched healthy controls were recruited to the study. Mean intima-media thickness of the common carotid artery (MIMT-CCA) and serum VEGF levels of all subjects were measured. Subclinical atherosclerosis was defined as having an MIMT-CCA >=0.8 mm. RESULTS: Serum VEGF levels in psoriatic patients were significantly higher compared with healthy controls (P < 0.0001). Psoriatic patients had significantly greater MIMT-CCA than healthy controls (P < 0.0001). Forty-five percent of patients and 6.7% of the healthy controls had subclinical atherosclerosis (P < 0.0001). In the patient group, subclinical atherosclerosis was significantly associated with serum VEGF levels, age, disease duration, and psoriasis area and severity index (PASI). CONCLUSION: This study supported the possible role of VEGF in the pathogenesis of subclinical atherosclerosis in psoriatic patients. PMID- 26135970 TI - Controlled electromechanical cell stimulation on-a-chip. AB - Stem cell research has yielded promising advances in regenerative medicine, but standard assays generally lack the ability to combine different cell stimulations with rapid sample processing and precise fluid control. In this work, we describe the design and fabrication of a micro-scale cell stimulator capable of simultaneously providing mechanical, electrical, and biochemical stimulation, and subsequently extracting detailed morphological and gene-expression analysis on the cellular response. This micro-device offers the opportunity to overcome previous limitations and recreate critical elements of the in vivo microenvironment in order to investigate cellular responses to three different stimulations. The platform was validated in experiments using human bone marrow mesenchymal stem cells. These experiments demonstrated the ability for inducing changes in cell morphology, cytoskeletal fiber orientation and changes in gene expression under physiological stimuli. This novel bioengineering approach can be readily applied to various studies, especially in the fields of stem cell biology and regenerative medicine. PMID- 26135971 TI - Contribution of Reduced Interleukin-10 Levels to the Pathogenesis of Osteomyelitis in Children with Sickle Cell Disease. AB - Osteomyelitis is a significant complication of sickle cell disease (SCD), and several factors contribute to its pathogenesis, including altered expression of proinflammatory and anti-inflammatory cytokines. In view of the role of interleukin-10 (IL-10) as an anti-inflammatory cytokine, we tested the notion that SCD osteomyelitis is associated with a reduction in IL-10 secretion and, hence, precipitation of a proinflammatory state. Study subjects comprised 52 SCD patients with confirmed diagnosis of osteomyelitis and 165 age- and gender matched SCD patients with negative histories of osteomyelitis. Results obtained showed that IL-10 serum levels in SCD osteomyelitis patients were significantly lower than those of control SCD patients. Receiver operating characteristic (ROC) analysis demonstrated that altered IL-10 serum levels predicted the development of osteomyelitis, and the mean area under ROC curves of IL-10 was 0.810 among SCD patients with osteomyelitis. A systematic shift in IL-10 serum levels toward lower values was seen in osteomyelitis cases, with an increased osteomyelitis risk associated with decreased IL-10 levels. Multivariate logistic regression analyses confirmed the independent association of reduced IL-10 with osteomyelitis after controlling for sickle hemoglobin (HbS), fetal hemoglobin (HbF), platelet count, and white blood cell (WBC) count. These data support the strong association of decreased IL-10 levels with osteomyelitis, thereby supporting a role for IL-10 in osteomyelitis follow-up. PMID- 26135972 TI - Evaluation of the Impact of Codon Optimization and N-Linked Glycosylation on Functional Immunogenicity of Pfs25 DNA Vaccines Delivered by In Vivo Electroporation in Preclinical Studies in Mice. AB - Plasmodium falciparum sexual stage surface antigen Pfs25 is a well-established candidate for malaria transmission-blocking vaccine development. Immunization with DNA vaccines encoding Pfs25 has been shown to elicit potent antibody responses in mice and nonhuman primates. Studies aimed at further optimization have revealed improved immunogenicity through the application of in vivo electroporation and by using a heterologous prime-boost approach. The goal of the studies reported here was to systematically evaluate the impact of codon optimization, in vivo electroporation, and N-linked glycosylation on the immunogenicity of Pfs25 encoded by DNA vaccines. The results from this study demonstrate that while codon optimization and in vivo electroporation greatly improved functional immunogenicity of Pfs25 DNA vaccines, the presence or absence of N-linked glycosylation did not significantly impact vaccine efficacy. These findings suggest that N-glycosylation of Pfs25 encoded by DNA vaccines is not detrimental to overall transmission-blocking efficacy. PMID- 26135973 TI - The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice. AB - The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8(+) T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-kappaB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines. PMID- 26135974 TI - Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections. AB - The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P < 0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min. PMID- 26135976 TI - Sand amendment enhances bioelectrochemical remediation of petroleum hydrocarbon contaminated soil. AB - Bioelectrochemical system is an emerging technology for the remediation of soils contaminated by petroleum hydrocarbons. However, performance of such systems can be limited by the inefficient mass transport in soil. Here we report a new method of sand amendment, which significantly increases both oxygen and proton transports, resulting to increased soil porosity (from 44.5% to 51.3%), decreased Ohmic resistance (by 46%), and increased charge output (from 2.5 to 3.5Cg( 1)soil). The degradation rates of petroleum hydrocarbons increased by up to 268% in 135d. The degradation of n-alkanes and polycyclic aromatic hydrocarbons with high molecular weight was accelerated, and denaturing gradient gel electrophoresis showed that the microbial community close to the air-cathode was substantially stimulated by the induced current, especially the hydrocarbon degrading bacteria Alcanivorax. The bioelectrochemical stimulation imposed a selective pressure on the microbial community of anodes, including that far from the cathode. These results suggested that sand amendment can be an effective approach for soil conditioning that will enhances the bioelectrochemical removal of hydrocarbons in contaminated soils. PMID- 26135977 TI - Highly porous activated carbons from resource-recovered Leucaena leucocephala wood as capacitive deionization electrodes. AB - Highly porous activated carbons were resource-recovered from Leucaena leucocephala (Lam.) de Wit. wood through combined chemical and physical activation (i.e., KOH etching followed by CO2 activation). This invasive species, which has severely damaged the ecological economics of Taiwan, was used as the precursor for producing high-quality carbonaceous electrodes for capacitive deionization (CDI). Carbonization and activation conditions strongly influenced the structure of chars and activated carbons. The total surface area and pore volume of activated carbons increased with increasing KOH/char ratio and activation time. Overgasification induced a substantial amount of mesopores in the activated carbons. In addition, the electrochemical properties and CDI electrosorptive performance of the activated carbons were evaluated; cyclic voltammetry and galvanostatic charge/discharge measurements revealed a typical capacitive behavior and electrical double layer formation, confirming ion electrosorption in the porous structure. The activated-carbon electrode, which possessed high surface area and both mesopores and micropores, exhibited improved capacitor characteristics and high electrosorptive performance. Highly porous activated carbons derived from waste L. leucocephala were demonstrated to be suitable CDI electrode materials. PMID- 26135975 TI - Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea. AB - Diarrhea continues to be a leading cause of death in children <5 years of age, and enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of children's diarrhea. Currently, there are no available vaccines against ETEC associated diarrhea. Whole-cell vaccine candidates have been under development but require further improvements because they provide inadequate protection and produce unwanted adverse effects. Meanwhile, a newer approach using polypeptide or subunit vaccine candidates focusing on ETEC colonization factor antigens (CFAs) and enterotoxins, the major virulence determinants of ETEC diarrhea, shows substantial promise. A conservative CFA/I adhesin tip antigen and a CFA MEFA (multiepitope fusion antigen) were shown to induce cross-reactive antiadhesin antibodies that protected against adherence by multiple important CFAs. Genetic fusion of toxoids derived from ETEC heat-labile toxin (LT) and heat-stable toxin (STa) induced antibodies neutralizing both enterotoxins. Moreover, CFA-toxoid MEFA polypeptides, generated by fusing CFA MEFA to an STa-LT toxoid fusion, induced antiadhesin antibodies that broadly inhibited adherence of the seven most important ETEC CFAs associated with about 80% of the diarrhea cases caused by ETEC strains with known CFAs. This same antigen preparation also induced antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea. Results from these studies suggest that polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. In addition, novel adhesins and mucin proteases have been investigated as potential alternatives or, more likely, additional antigens for ETEC subunit vaccine development. PMID- 26135978 TI - Electric Permittivity and Dynamic Mobility of Dilute Suspensions of Platelike Gibbsite Particles. AB - In this work we discuss the electrokinetic evaluation of model platelike particles. By model particles we mean homogeneous and controlled size and shape. The electrokinetic analysis in such complex geometries cannot be limited to a single data point as in usual electrophoresis in constant (dc) fields. The information can be made much richer if alternating (ac) fields with a sufficiently wide range of frequencies are used. In this case, two techniques can be applied: one is the determination of the frequency spectrum of the electric permittivity or dielectric constant (low-frequency dielectric dispersion), and the other is the electroacoustics of suspensions and the determination of the frequency dispersion of the electrophoretic mobility (dynamic or ac mobility). In this work, these techniques are used with planar gibbsite (gamma-Al(OH)3) particles, modeled as oblate spheroids with a small aspect ratio. As in other laminar minerals, a particular charge distribution, differing between edges and faces, gives rise to very peculiar electrokinetic behavior. It is found that pH 7 approximately separates two distinct field responses: below that pH the dielectric dispersion and dynamic mobility data are consistent with the existence of individual, highly charged platelets, with charge mainly originating on edge surfaces. At pH 4, a low-frequency relaxation is observed, which must originated from larger particles. It is suggested that these are individual ones bridged by negatively charged fiberlike structures, coming from the partial decomposition of gibbsite particles. On the other side of the measured pH spectrum, the overall charge of the particles is low, and this probably produces aggregates with a relatively large average size, with relaxation frequencies on the low side. This is confirmed by dynamic mobility data, showing that a coherent picture of the nanostructure can be reached by combining the two techniques. PMID- 26135979 TI - Use of Octreotide for the Management of Chyle Fistula Following Neck Dissection. AB - IMPORTANCE: Chyle fistula is an uncommon complication of neck surgery. A variety of management strategies have been described, including diet restriction, parenteral nutrition, use of pressure dressings, and revision surgery. Octreotide has been used with success in patients with neck and thoracic chyle fistulas, but data regarding efficacy in neck chyle fistulas are lacking. OBJECTIVE: To evaluate the efficacy of octreotide for use in patients with postoperative chyle fistulas. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 12 patients who received octreotide for neck chylous fistula after neck dissection was performed during the period 2004 through 2014 at 2 tertiary care academic hospitals. EXPOSURES: Patients with postoperative neck chyle fistulas were given a restricted diet and subcutaneous octreotide. MAIN OUTCOMES AND MEASURES: The main outcome was fistula closure rate, defined as fistula resolution without surgical intervention. Secondary outcomes of fistula duration (days from detection until resolution), length of hospital stay (surgery to discharge), and treatment complications were also examined. RESULTS: All 12 patients had resolution of their neck chyle fistula with octreotide therapy without need for revision surgery. Mean (SD) hospital stay was 8.7 (4.76) days, with a range of 3 to 18 days. The chyle fistula resolved after a mean (range) 5.5 (2-11) days. Self resolving nausea was encountered in 1 patient from octreotide use, and 1 patient developed a salivary fistula as a result of the chylous fistula. CONCLUSIONS AND RELEVANCE: In these patients, octreotide was safe and effective in resolving neck chylous fistulas. Octreotide therapy appears superior to traditional conservative measures of diet restriction and pressure dressings when compared with literature rates. A prospective study is needed to confirm results, but octreotide therapy should be considered as first-line conservative management for neck chyle fistulas that occur after neck surgery. PMID- 26135981 TI - Evolutionarily Conserved Pattern of Interactions in a Protein Revealed by Local Thermal Expansion Properties. AB - The way in which the network of intramolecular interactions determines the cooperative folding and conformational dynamics of a protein remains poorly understood. High-pressure NMR spectroscopy is uniquely suited to examine this problem because it combines the site-specific resolution of the NMR experiments with the local character of pressure perturbations. Here we report on the temperature dependence of the site-specific volumetric properties of various forms of staphylococcal nuclease (SNase), including three variants with engineered internal cavities, as measured with high-pressure NMR spectroscopy. The strong temperature dependence of pressure-induced unfolding arises from poorly understood differences in thermal expansion between the folded and unfolded states. A significant inverse correlation was observed between the global thermal expansion of the folded proteins and the number of strong intramolecular hydrogen bonds, as determined by the temperature coefficient of the backbone amide chemical shifts. Comparison of the identity of these strong H bonds with the co-evolution of pairs of residues in the SNase protein family suggests that the architecture of the interactions detected in the NMR experiments could be linked to a functional aspect of the protein. Moreover, the temperature dependence of the residue-specific volume changes of unfolding yielded residue-specific differences in expansivity and revealed how mutations impact intramolecular interaction patterns. These results show that intramolecular interactions in the folded states of proteins impose constraints against thermal expansion and that, hence, knowledge of site-specific thermal expansivity offers insight into the patterns of strong intramolecular interactions and other local determinants of protein stability, cooperativity, and potentially also of function. PMID- 26135980 TI - Brain microvascular endothelium induced-annexin A1 secretion contributes to small cell lung cancer brain metastasis. AB - Small cell lung cancer is the most aggressive histologic subtype of lung cancer, with a strong predilection for metastasizing to brain early. However, the cellular and molecular basis is poorly known. Here, we provided evidence to reveal the role of annexin A1 in small cell lung cancer metastasis to brain. Firstly, the elevated annexin A1 serum levels in small cell lung cancer patients were associated with brain metastasis. The levels of annexin A1 were also upregulated in NCI-H446 cells, a small cell lung cancer cell line, upon migration into the mice brain. More interestingly, annexin A1 was secreted by NCI-H446 cells in a time-dependent manner when co-culturing with human brain microvascular endothelial cells, which was identified with the detections of annexin A1 in the co-cultured cellular supernatants by ELISA and western blot. Further results showed that blockage of annexin A1 in the co-cultured cellular supernatants using a neutralized antibody significantly inhibited NCI-H446 cells adhesion to brain endothelium and its transendothelial migration. Conversely, the addition of Ac2 26, an annexin A1 mimic peptide, enhanced these effects. Furthermore, knockdown of annexin A1 in NCI-H446 cells prevented its transendothelial migration in vitro and metastasis to mice brain in vivo. Our data showed that small cell lung cancer cell in brain microvasculature microenvironment could express much more annexin A1 and release it outside, which facilitated small cell lung cancer cell to gain malignant properties of entry into brain. These findings provided a potential target for the management of SCLC brain metastasis. PMID- 26135982 TI - How 'some garlic' becomes 'a garlic' or 'some onion': Mass and count processing in aphasia. AB - This paper informs our understanding of the representation and processing of mass and count nouns through an investigation of the underlying causes of mass/count specific impairments in in two people with aphasia, DEH and GEC. The factors influencing the production of mass and count nouns and noun phrases was comprehensively assessed. The results showed that GEC's impairment affected mass noun naming, resulting in the production of semantic paraphasias and no responses. In contrast, DEH frequently substituted mass determiners with count determiners leading to ungrammatical noun phrases. In comparison to younger control group, a control group of older adults showed similar difficulties to DEH with mass noun phrases, although less severe, indicating effects of cognitive ageing on lexical and semantic processing. DEH and the elderly controls' results replicate and support previous findings regarding the lexical-syntactic representation of mass/count information. GEC's difficulties extend these findings by providing additional evidence for a semantic component in the representation of countability (e.g., a semantic feature/concept COUNTABLE for count nouns, UNCOUNTABLE for mass nouns) which contributes to mass and count noun selection. GEC's mass noun difficulties are suggested to result from weaker connection strength between noun lemmas and mass concepts compared to count concepts as a result of the overall lower frequency distribution of mass nouns. PMID- 26135983 TI - Choroidal neovascularisation as an unusual ophthalmic manifestation of cat scratch disease in an 8-year-old girl. AB - To report the first case of choroidal neovascularisation (CNV) that appeared during the primary Bartonella henselae infection in an 8-year-old girl. An 8-year old girl was referred to our clinic complaining of a central scotoma in the right eye. Fundus examination revealed a bilateral disc oedema and in the right eye neuroretinitis with macular star and CNV, which was confirmed by fluorescein angiography. The optical coherence tomography revealed the presence of macular serous retinal detachment. Laboratory analysis showed rising IgM and IgG titres for B. henselae. Cat-scratch disease was diagnosed, and an 8-week treatment with azithromycin was initiated. In addition, an intravitreal injection of ranibizumab was performed in the right eye to treat the CNV. A month later, we decided to administer a systemic antibiotic again for an additional 5 months, due to the persistence of papillitis. Cat-scratch disease should be considered among the different causes of inflammatory CNV secondary to infectious uveitis. Our case was the first described in the literature in which a CNV appeared during the primary infection and not as a later complication. The combination of systemic antibiotic treatment with intravitreal anti-VEGF therapy was a successful choice because it allowed us to obtain the complete resolution of neuroretinitis, associated with the scarring of the choroidal neovascular membrane, with a final visual acuity of 20/20 in both eyes. PMID- 26135984 TI - Assembling of Holotrichia parallela (dark black chafer) midgut tissue transcriptome and identification of midgut proteins that bind to Cry8Ea toxin from Bacillus thuringiensis. AB - Holotrichia parallela is one of the most severe crop pests in China, affecting peanut, soybean, and sweet potato crops. Previous work showed that Cry8Ea toxin is highly effective against this insect. In order to identify Cry8Ea-binding proteins in the midgut cells of H. parallela larvae, we assembled a midgut tissue transcriptome by high-throughput sequencing and used this assembled transcriptome to identify Cry8Ea-binding proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS). First, we obtained de novo sequences of cDNAs from midgut tissue of H. parallela larvae and used available cDNA data in the GenBank. In a parallel assay, we obtained 11 Cry8Ea-binding proteins by pull-down assays performed with midgut brush border membrane vesicles. Peptide sequences from these proteins were matched to the H. parallela newly assembled midgut transcriptome, and 10 proteins were identified. Some of the proteins were shown to be intracellular proteins forming part of the cell cytoskeleton and/or vesicle transport such as actin, myosin, clathrin, dynein, and tubulin among others. In addition, an apolipophorin, which is a protein involved in lipid metabolism, and a novel membrane-bound alanyl aminopeptidase were identified. Our results suggest that Cry8Ea-binding proteins could be different from those characterized for Cry1A toxins in lepidopteran insects. PMID- 26135986 TI - Class IV polyhydroxyalkanoate (PHA) synthases and PHA-producing Bacillus. AB - This review highlights the recent investigations of class IV polyhydroxyalkanoate (PHA) synthases, the newest classification of PHA synthases. Class IV synthases are prevalent in organisms of the Bacillus genus and are composed of a catalytic subunit PhaC (approximately 40 kDa), which has a PhaC box sequence ([GS]-X-C-X [GA]-G) at the active site, and a second subunit PhaR (approximately 20 kDa). The representative PHA-producing Bacillus strains are Bacillus megaterium and Bacillus cereus; the nucleotide sequence of phaC and the genetic organization of the PHA biosynthesis gene locus are somewhat different between these two strains. It is generally considered that class IV synthases favor short-chain-length monomers such as 3-hydroxybutyrate (C4) and 3-hydroxyvalerate (C5) for polymerization, but can polymerize some unusual monomers as minor components. In Escherichia coli expressing PhaRC from B. cereus YB-4, the biosynthesized PHA undergoes synthase-catalyzed alcoholytic cleavage using endogenous and exogenous alcohols. This alcoholysis is thought to be shared among class IV synthases, and this reaction is useful not only for the regulation of PHA molecular weight but also for the modification of the PHA carboxy terminus. The novel properties of class IV synthases will open up the possibility for the design of new PHA materials. PMID- 26135985 TI - Comparative phenomics and targeted use of genomics reveals variation in carbon and nitrogen assimilation among different Brettanomyces bruxellensis strains. AB - Recent studies have suggested a correlation between genotype groups of Brettanomyces bruxellensis and their source of isolation. To further explore this relationship, the objective of this study was to assess metabolic differences in carbon and nitrogen assimilation between different B. bruxellensis strains from three beverages, including beer, wine, and soft drink, using Biolog Phenotype Microarrays. While some similarities of physiology were noted, many traits were variable among strains. Interestingly, some phenotypes were found that could be linked to strain origin, especially for the assimilation of particular alpha- and beta-glycosides as well as alpha- and beta-substituted monosaccharides. Based upon gene presence or absence, an alpha-glucosidase and beta-glucosidase were found explaining the observed phenotypes. Further, using a PCR screen on a large number of isolates, we have been able to specifically link a genomic deletion to the beer strains, suggesting that this region may have a fitness cost for B. bruxellensis in certain fermentation systems such as brewing. More specifically, none of the beer strains were found to contain a beta-glucosidase, which may have direct impacts on the ability for these strains to compete with other microbes or on flavor production. PMID- 26135987 TI - Investment incentives and the implementation of the Framework Convention on Tobacco Control: evidence from Zambia. AB - PURPOSE: Policy misalignment across different sectors of government serves as one of the pivotal barriers to WHO Framework Convention on Tobacco Control (FCTC) implementation. This paper examines the logic used by government officials to justify investment incentives to increase tobacco processing and manufacturing in the context of FCTC implementation in Zambia. METHODS: We conducted qualitative semistructured interviews with key informants from government, civil society and intergovernmental economic organisations (n=23). We supplemented the interview data with an analysis of public documents pertaining to the policy of economic development in Zambia. RESULTS: We found gross misalignments between the policies of the economic sector and efforts to implement the provisions of the FCTC. Our interviews uncovered the rationale used by officials in the economic sector to justify providing economic incentives to bolster tobacco processing and manufacturing in Zambia: (1) tobacco is not consumed by Zambians/tobacco is an export commodity, (2) economic benefits outweigh health costs and (3) tobacco consumption is a personal choice. CONCLUSIONS: Much of the struggle Zambia has experienced in implementing the FCTC can be attributed to misalignments between the economic and health sectors. Zambia's development agenda seeks to bolster agricultural processing and manufacturing. Tobacco control proponents must recognise and work within this context in order to foster productive strategies with those working on tobacco supply issues. These findings are broadly applicable to the global context. It is important that the Ministry of Health monitors the tobacco policy of and engages with these sectors to find ways of harmonising FCTC implementation. PMID- 26135989 TI - Freed up to be truly effective ward leaders. PMID- 26135988 TI - Synthesis and unique reversible splitting of 14-membered cyclic aminomethylphosphines on to 7-membered heterocycles. AB - A novel type of 14-membered cyclic polyphosphine, namely 1,8-diaza-3,6,10,13 tetraphosphacyclotetradecanes 2a-4ahas been synthesized by the condensation of 1,2-bis(phenylphosphino)ethane, formaldehyde and alkylamines (isopropylamine, ethylamine and cyclohexylamine) as a RRRR/SSSS-stereoisomer. The structure of macrocycle 2a was investigated by NMR-spectroscopy and X-ray crystal structure analysis. The unique reversible processes of macrocycles 2a-4a splitting onto the corresponding rac- (2b-4b) and meso- (2c-4c) stereoisomers of 1-aza-3,6 diphosphacycloheptanes were discovered. PMID- 26135990 TI - 'Open culture is needed to allow staff to learn from their mistakes'. PMID- 26135991 TI - College deplores decision to end NICE work on safe nurse staffing. PMID- 26135992 TI - Supervisor status boosts ward sisters' effectiveness and authority of role. PMID- 26135993 TI - RCN fellowships for exceptional professionals. PMID- 26135994 TI - Regulators' regulator urges caution on revalidation. PMID- 26135995 TI - Hands off our unsocial hours pay, college congress tells government. PMID- 26135996 TI - Mentors key to unlocking equality. PMID- 26135997 TI - NMC will take action over dishonesty, barrister warns. PMID- 26135998 TI - New guidance on end of life care. PMID- 26136000 TI - Community nurses given little or no protection from abusive patients. PMID- 26136001 TI - ICN president hopes to lure RCN back. PMID- 26136002 TI - College guidance strives to fill vacuum in end of life care protocol. PMID- 26136008 TI - Pressure ulcers. PMID- 26136009 TI - Work together to prevent infection. PMID- 26136010 TI - What about nursing's 'fourth dimension'? PMID- 26136011 TI - Vital signs of the times. PMID- 26136020 TI - Bethlem Museum of the Mind. PMID- 26136023 TI - SIGN app. PMID- 26136024 TI - Shiver me timbers, this congress was worth the trip and no mistake. PMID- 26136025 TI - Staff who fail NMC revalidation need to know what to do next. PMID- 26136026 TI - A memorable occasion for Muslim nurses because of RCN's efforts. PMID- 26136028 TI - The Queen's nurse conference is being held at the RCGP in London. PMID- 26136029 TI - The use of cameras is the wrong way to expose poor practice. PMID- 26136030 TI - Anyone out there from Union College Hospital set 277 of 1985? PMID- 26136031 TI - My working hours prove that district nurses do work at night. PMID- 26136033 TI - Use of diaries in research. AB - This article presents an overview of the diary as a popular method for data collection in nursing and health research. The context for using diaries as a data collection tool is considered and the nature and purpose of the diary and its relationship with health care are examined. The author reflects on different types of diary and their use in data collection, and explores the advantages and disadvantages of using a diary approach to data collection in health care. PMID- 26136034 TI - Milk allergy in adults and children. AB - Cow's milk allergy is common in children and rare in adults. The clinical features of cow's milk allergy are varied and they include anaphylaxis, gastrointestinal symptoms and atopic dermatitis. The prevalence of cow's milk allergy is difficult to ascertain, based on self-reported symptoms that are not subsequently confirmed by diagnostic testing. The gold-standard diagnostic test is the double-blind placebo-controlled food challenge. Avoidance of milk and milk products is the main therapy. Nutritional considerations are important in both children and adults, as is recognising the potential for resolution of cow's milk allergy. Providing evidence-based advice and support to individuals and their families and carers is central to managing cow's milk allergy. PMID- 26136035 TI - Psychological needs of people living with cancer. AB - The mental health of patients with cancer is a vital part of their overall wellbeing. Unmet mental health needs have an adverse effect on a patient's ability to cope with illness and its treatment and contribute to an increased burden on health services. Low staffing levels and inadequate training and support in the use of psychological skills may result in patients' psychological difficulties going unnoticed. This article aims to improve nurses' understanding of psychosocial issues that may arise during a diagnosis of cancer and its treatment and examines national guidance on the provision of psychological support to patients with cancer and their families. The author discusses best practice in psychological assessment and intervention and the importance of continuing professional development and self-care. PMID- 26136036 TI - Healthcare surveillance. PMID- 26136037 TI - Less continence stress. PMID- 26136038 TI - What is your personality type? PMID- 26136041 TI - Every student can help prevent pressure ulcers. PMID- 26136042 TI - Improving assisted reproductive technology pregnancy rates: excluding aneuploid and interrogating euploid embryos. PMID- 26136043 TI - Polycistronic artificial miRNA-mediated resistance to Wheat dwarf virus in barley is highly efficient at low temperature. AB - Infection of Wheat dwarf virus (WDV) strains on barley results in dwarf disease, imposing severe economic losses on crop production. As the natural resistance resources against this virus are limited, it is imperative to elaborate a biotechnological approach that will provide effective and safe immunity to a wide range of WDV strains. Because vector insect-mediated WDV infection occurs during cool periods in nature, it is important to identify a technology which is effective at lower temperature. In this study, we designed artificial microRNAs (amiRNAs) using a barley miRNA precursor backbone, which target different conservative sequence elements of the WDV strains. Potential amiRNA sequences were selected to minimize the off-target effects and were tested in a transient sensor system in order to select the most effective constructs at low temperature. On the basis of the data obtained, a polycistronic amiRNA precursor construct (VirusBuster171) was built expressing three amiRNAs simultaneously. The construct was transformed into barley under the control of a constitutive promoter. The transgenic lines were kept at 12-15 degrees C to mimic autumn and spring conditions in which major WDV infection and accumulation take place. We were able to establish a stable barley transgenic line displaying resistance to insect-mediated WDV infection. Our study demonstrates that amiRNA technology can be an efficient tool for the introduction of highly efficient resistance in barley against a DNA virus belonging to the Geminiviridae family, and this resistance is effective at low temperature where the natural insect vector mediates the infection process. PMID- 26136044 TI - Effect of methotrexate on rostral migratory stream in newborn rats. AB - Two-day-old rats were treated with subcutaneous injections of methotrexate (MTX) 5 mg/kg and 150 mg/kg, and their rostral migratory streams (RMS) were examined time-dependently. MTX treatment increased pyknotic and TUNEL-positive cells and decreased mitotic and phospho-Histone H3-positive cells at almost all time points in the vertical arm, elbow and horizontal arm regions of the RMS. There were more TUNEL-positive cells ratio in the MTX 150 mg/kg group than in the MTX 5 mg/kg group. Treatment with MTX 150 mg/kg decreased the cellularity in the vertical arm region on Postnatal day (PD) 4, but that with the MTX 5 mg/kg did not. TUNEL positive cells ratio was the highest in the vertical arm region, followed by elbow and horizontal regions in both MTX-treated groups. TUNEL-positive cells ratio in the vertical arm and elbow regions reached their peaks on PD 4 in both MTX-treated groups, and both MTX-treatments significantly decreased Phospho Histone H3-positive cells ratio on PDs 2.5 and 3 in the vertical arm, elbow and horizontal arm regions. The phospho-Histone H3-positive cells ratio in the vertical arm region recovered on PD4 in the MTX 150 mg/kg group. These findings suggested that RMS required a great amount of folic acid on PD 2 and that the folic acid-requirement differed depending on the anatomical region of the RMS. To our knowledge, this is the first report demonstrating the effect of MTX on the RMS and the necessity of the folic acid metabolism on RMS development in newborn rats. PMID- 26136045 TI - Team of rivals in chipping sparrows? A comment on Goodwin & Podos. PMID- 26136046 TI - Reply to Akcay & Beecher: yes, team of rivals in chipping sparrows. PMID- 26136047 TI - You talkin' to me? Interactive playback is a powerful yet underused tool in animal communication research. AB - Over the years, playback experiments have helped further our understanding of the wonderful world of animal communication. They have provided fundamental insights into animal behaviour and the function of communicative signals in numerous taxa. As important as these experiments are, however, there is strong evidence to suggest that the information conveyed in a signal may only have value when presented interactively. By their very nature, signalling exchanges are interactive and therefore, an interactive playback design is a powerful tool for examining the function of such exchanges. While researchers working on frog and songbird vocal interactions have long championed interactive playback, it remains surprisingly underused across other taxa. The interactive playback approach is not limited to studies of acoustic signalling, but can be applied to other sensory modalities, including visual, chemical and electrical communication. Here, I discuss interactive playback as a potent yet underused technique in the field of animal behaviour. I present a concise review of studies that have used interactive playback thus far, describe how it can be applied, and discuss its limitations and challenges. My hope is that this review will result in more scientists applying this innovative technique to their own study subjects, as a means of furthering our understanding of the function of signalling interactions in animal communication systems. PMID- 26136048 TI - Selective spore germination on shoots of Homalothecium lutescens, a moss with dwarf males. AB - Spores from three bryophyte species with dwarf males (Homalothecium lutescens, Homalothecium sericeum and Isothecium alopecuroides) were sown on shoots of H. lutescens in vitro. After 10 months, presence and fertility of dwarf plants were scored. Spores of the more distantly related I. alopecuroides were unable to develop into dwarf plants on H. lutescens. Spores of both H. lutescens and H. sericeum developed into dwarf plants. In fact, dwarf plants of H. sericeum were both more abundant and more often fertile than those of H. lutescens. The ability of H. sericeum spores to develop into dwarf males on shoots of H. lutescens suggests a possible pathway for hybridization between the two species. On the other hand, the inability of I. alopecuroides to develop into dwarf males on shoots of H. lutescens suggests that regulation of spore germination and dwarf male development on host shoots is associated with the degree of relatedness between species. PMID- 26136050 TI - The murine excisional wound model: Contraction revisited. AB - Rodent models of healing are considered limited because of the perception that rodent wounds heal by contraction while humans heal by reepithelialization The purpose of this report is to present evidence that simple murine excisional wounds provide a valid and reproducible wound model that heals by both contraction and reepithelialization. Previous studies have shown that, although rodent wounds contract by up to 80%, much of this contraction occurs only after epithelial closure. To confirm these previous findings, we measured re epithelialization and contraction in three separate mouse strains, (BALB/c, db/+, and db/db); reepithelialization and contraction each accounted for ~40 to 60% of the initial closure of full thickness excisional wounds. After closure, the wound continues to contract and this provides the impression of dominant closure by contraction. In conclusion, the simple excisional rodent wound model produces a well defined and readily identifiable wound bed over which the process of reepithelialization is clearly measurable. PMID- 26136049 TI - Degeneration of proprioceptive sensory nerve endings in mice harboring amyotrophic lateral sclerosis-causing mutations. AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets the motor system. Although much is known about the effects of ALS on motor neurons and glial cells, little is known about its effect on proprioceptive sensory neurons. This study examines proprioceptive sensory neurons in mice harboring mutations associated with ALS, in SOD1(G93A) and TDP43(A315T) transgenic mice. In both transgenic lines, we found fewer proprioceptive sensory neurons containing fluorescently tagged cholera toxin in their soma five days after injecting this retrograde tracer into the tibialis anterior muscle. We asked whether this is due to neuronal loss or selective degeneration of peripheral nerve endings. We found no difference in the total number and size of proprioceptive sensory neuron soma between symptomatic SOD1(G93A) and control mice. However, analysis of proprioceptive nerve endings in muscles revealed early and significant alterations at Ia/II proprioceptive nerve endings in muscle spindles before the symptomatic phase of the disease. Although these changes occur alongside those at alpha-motor axons in SOD1(G93A) mice, Ia/II sensory nerve endings degenerate in the absence of obvious alterations in alpha-motor axons in TDP43(A315T) transgenic mice. We next asked whether proprioceptive nerve endings are similarly affected in the spinal cord and found that nerve endings terminating on alpha-motor neurons are affected during the symptomatic phase and after peripheral nerve endings begin to degenerate. Overall, we show that Ia/II proprioceptive sensory neurons are affected by ALS-causing mutations, with pathological changes starting at their peripheral nerve endings. PMID- 26136052 TI - Evaluating a range of learning schedules: hybrid training schedules may be as good as or better than distributed practice for some tasks. AB - We investigated theoretically and empirically a range of training schedules on tasks with three knowledge types: declarative, procedural, and perceptual-motor. We predicted performance for 6435 potential eight-block training schedules with ACT-R's declarative memory equations. Hybrid training schedules (schedules consisting of distributed and massed practice) were predicted to produce better performance than purely distributed or massed training schedules. The results of an empirical study (N = 40) testing four exemplar schedules indicated a more complex picture. There were no statistical differences among the groups in the declarative and procedural tasks. We also found that participants in the hybrid practice groups produced reliably better performance than ones in the distributed practice group for the perceptual-motor task--the results indicate training schedules with some spacing and some intensiveness may lead to better performance, particularly for perceptual-motor tasks, and that tasks with mixed types of knowledge might be better taught with a hybrid schedule. PRACTITIONER SUMMARY: We explored distributed and massed training schedules as well as hybrids between them with respect to three knowledge types based on theories and an empirical study. The results suggest that industrial and operator training in complex tasks need not and probably should not be done on a distributed training schedule. PMID- 26136051 TI - Folding and function in alpha/beta-peptides: targets and therapeutic applications. AB - Combining natural alpha-amino acid residues and unnatural beta-amino acid residues in a single chain leads to heterogeneous-backbone oligomers called alpha/beta-peptides. Despite their unnatural backbones, alpha/beta-peptides can manifest a variety of folding patterns and biological functions reminiscent of natural peptides and proteins. Moreover, incorporation of beta-residues can impart useful properties to the oligomer such as improved stability to degradation by protease enzymes. alpha/beta-Peptides have been developed that engage diverse biological targets, including proteins involved in apoptotic signalling, HIV-cell fusion, hormone signalling, and angiogenesis. For some systems, promising results obtained in vitro have paved the way for demonstrated activity in vivo, where alpha/beta-peptides show equal potency and improved duration of effect compared to alpha-peptide counterparts. PMID- 26136053 TI - Formation, compression and surface melting of colloidal clusters by active particles. AB - We demonstrate with experiments and numerical simulations that the structure and dynamics of a suspension of passive particles is strongly altered by adding a very small (<1%) number of active particles. With increasing passive particle density, we observe first the formation of dynamic clusters comprised of passive particles being surrounded by active particles, then the merging and compression of these clusters, and eventually the local melting of crystalline regions by enclosed active particles. PMID- 26136054 TI - Probing the nanoscale Schottky barrier of metal/semiconductor interfaces of Pt/CdSe/Pt nanodumbbells by conductive-probe atomic force microscopy. AB - The electrical nature of the nanoscale contact between metal nanodots and semiconductor rods has drawn significant interest because of potential applications for metal-semiconductor hybrid nanostructures in energy conversion or heterogeneous catalysis. Here, we studied the nanoscale electrical character of the Pt/CdSe junction in Pt/CdSe/Pt nanodumbbells on connected Au islands by conductive-probe atomic force microscopy under ultra-high vacuum. Current-voltage plots measured in contact mode revealed Schottky barrier heights of individual nanojunctions of 0.41 +/- 0.02 eV. The measured value of the Schottky barrier is significantly lower than that of planar thin-film diodes because of a reduction in the barrier width and enhanced tunneling probability at the interface. PMID- 26136055 TI - Novel risk markers and mediators in coronary disease and stroke. PMID- 26136056 TI - Salim Yusuf MD: the physician who wants to improve the world's cardiovascular health. PMID- 26136057 TI - Can Diabetes Heal?- From Observations to Perspectives. AB - Diabetes, both type 1 and type 2, is considered a chronic incurable disease. Complete cure would bring enormous benefits in terms of both the prevention of complications and reduction of the very high resulting social cost. Recent advances in the study of autoimmune mechanisms for type 1 and some non-medical therapeutic approaches for type 2 shed light on the pathophysiology and induce optimism concerning a possible cure in the not-too-distant future. This perspective highlights the main mechanisms involved in the pathophysiology of the two forms of diabetes, as the latest research has revealed, and the resulting possible therapeutic strategies that may be involved in obtaining a cure. PMID- 26136058 TI - Four new spiroaxane sesquiterpenes and one new rosenonolactone derivative from cultures of Basidiomycete Trametes versicolor. AB - Four new spiroaxane sesquiterpenes, tramspiroins A-D (1-4), one new rosenonolactone 15,16-acetonide (5), and the known drimane sesquiterpenes isodrimenediol (6) and funatrol D (7) have been isolated from the cultures of Basidiomycete Trametes versicolor. The structures of new compounds were elucidated by means of spectroscopic methods. Compounds 1-7 were investigated for their cytotoxicities against five human cancer cell lines. PMID- 26136059 TI - Semi-synthetic derivatives of natural isoflavones from Maclura pomifera as a novel class of PDE-5A inhibitors. AB - Natural (iso)flavonoids have been recently reported to inhibit cyclic nucleotide phosphodiesterases (PDEs) and induce vasorelaxation, albeit the results described in the literature are discordant. The cGMP-selective isoform PDE-5A, in particular, represents the target of sildenafil and its analogues in the treatment of erectile dysfunction (ED) and pulmonary hypertension by promoting relaxation in vascular smooth muscle through the activation of the NO/cGMP pathway. We undertook this study to verify if osajin and pomiferin, two natural prenylated isoflavones and major constituents of Maclura pomifera extracts previously investigated for their anticancer, antibacterial and antidiabetic properties, show inhibitory activity on PDE-5A. These two isoflavones were isolated from the plant extracts and then synthetically modified to obtain a set of semi-synthetic derivatives with slight and focused modifications on the natural scaffold. The compounds were at first screened against PDE-5A in vitro and, based on the encouraging results, further tested for their relaxant effect on isolated rat artery rings. Computational docking studies were also carried out to explore the mode of interaction with the target protein. The obtained data were compared to the behaviour of the well-known PDE-5A inhibitor sildenafil. Our results demonstrate that semi-synthetic derivatives of osajin and pomiferin show an inhibitory effect on the isolated enzyme that, for some of the compounds, is accompanied by a vasorelaxant activity. Based on our findings, we propose the here described isoflavones as potential lead compounds for the development, starting from natural scaffolds, of a new class of PDE-5A inhibitors with vasorelaxant properties. PMID- 26136060 TI - Metabolites from Combretum dolichopetalum and its associated endophytic fungus Nigrospora oryzae--Evidence for a metabolic partnership. AB - A new altersolanol derivative, 4-dehydroxyaltersolanol A (9), along with two known sesquiterpenoids, (S)-7'-hydroxyabscisic acid (7) and (S)-abscisic acid (8) were obtained from the endophytic fungus, Nigrospora oryzae, isolated from leaves of Combretum dolichopetalum. The host plant yielded six known compounds including ellagic acid (1), 3, 3', 4-tri-O-methylellagic acid (2), arjunolic acid (3), 4' dihydrophaseic acid (4), echinulin (5) and arestrictin B (6). Close structural similarities with regard to compounds 4, 7 and 8 were observed between the metabolites from the host plant and those of the endophytic fungus. Furthermore compounds 5 and 6 are related to alkaloids isolated from N. oryzae previously thus stressing the notion that some of the isolated plant metabolites may actually be of fungal origin. The structures of the isolated compounds were established by spectroscopic methods including 1D, 2D NMR, MS, and by comparison with the literature. 4-Dehydroxyaltersolanol A (9) and 3, 3', 4-tri-O methylellagic acid (2) showed cytotoxicity against L5178Y mouse lymphoma cells with IC50 values of 9.4 and 29.0 MUM, respectively. PMID- 26136061 TI - Antibacterial monoterpenoid indole alkaloids from Alstonia scholaris cultivated in temperate zone. AB - Three new monoterpenoid indole alkaloids, named normavacurine-21-one (1), 5 hydroxy-19, 20-E-alschomine (2), and 5-hydroxy-19, 20-Z-alschomine (3), together with thirteen known indole alkaloids (4-16) were isolated from the leaves of Alstonia scholaris cultivated in Kunming. Their structures were elucidated on the basis of extensive spectroscopic analysis, as well as by comparison with the reported spectroscopic data. The leaves of A. scholaris cultivated in Kunming, contained picrinine-type alkaloids, scholaricin-type alkaloids and nareline as major alkaloids. New compounds 1-3 might be derived from a common biogenetic precursor (5). Compounds 1, 5 and 10 exhibited significant antibacterial activity against Enterococcus faecalis, and 3, 9 and 14 against Pseudomonas aeruginosa with an MIC value of 0.781 MUg/mL, while 14 showed moderate activity against Klepsiella pneumonia with an MIC value of 1.56 MUg/mL. PMID- 26136062 TI - Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis. AB - Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker--the c-terminus telopeptide of type II collagen (CTXII)--magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 MUL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed tenfold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat. PMID- 26136063 TI - Effect of birth weight on life-course blood pressure levels among children born premature: the Cardiovascular Risk in Young Finns Study. AB - OBJECTIVES: Both fetal growth restriction and prematurity have been associated with elevated blood pressure (BP). However, their combined effects on adult BP are unclear. METHODS: Our analyses were based on 1756 participants in the population-based Cardiovascular Risk in Young Finns Study who had information on birth weight and gestational age, together with longitudinal data on cardiovascular risk markers from age 3-18 years in 1980 to age 34-49 years in 2011. Three groups were defined by birth data: those born at term (term); those born preterm (<37 weeks) with an appropriate birth weight (>-1 SD z score according to national sex and gestational week-stratified data) for gestational age (preterm appropriate birth weight for gestational age); and those born preterm with low birth weight (<=-1 SD z score) for gestational age [preterm small birth weight for gestational age (SGA)]. RESULTS: There were no differences between the three groups in BP at baseline, but at the 31-year follow-up (mean age 41 years), mean SBP in the preterm SGA group was 7.2 mmHg (95% confidence interval = 2.3-12.1 mmHg, P = 0.004) higher than the preterm appropriate birth weight for gestational age group and 7.3 mmHg (95% confidence interval = 5.2-9.4 mmHg, P < 0.0001) higher than the term group, adjusted for age and sex. In addition, preterm SGA individuals had a higher prevalence of adult hypertension compared with those born at term (36.9 vs. 25.4%; age, sex, and risk factors adjusted P = 0.006). CONCLUSION: These longitudinal data suggest that elevated BP levels associated with prematurity are more likely to be present in those with fetal growth restriction. PMID- 26136064 TI - Former male elite athletes and risk of hypertension in later life. AB - OBJECTIVE: The aim of this study was to assess whether a former career as an elite athlete protects from hypertension in later life. We hypothesized that vigorous physical activity during young adulthood protects against hypertension later in life. METHODS: The study population (n = 3440) consists of 2037 former male elite athletes and 1403 matched controls. Of those, 599 (392 former athletes, 207 controls) participated in a clinical study in 2008. The athletes were divided into three groups: endurance, mixed and power sports. Assessment of hypertension was based on athletes' entitlement to reimbursable antihypertensive medication from the Finnish Social Insurance Institution; among the clinical study participants, this was also based on self-reported current use of antihypertensive drugs or measured hypertension. The current volume of leisure time physical activity (LTPA) was determined by questionnaires. RESULTS: Among the participants, the former athletes had lower age-adjusted prevalence of hypertension than the controls [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.49-0.98] and the endurance athletes had the lowest OR (OR 0.43, 95% CI 0.23-0.80). OR for the prevalence of hypertension decreased (OR 0.90, 95% CI 0.84 0.96 per 10 metabolic equivalent hours/week) when there was an increase in the volume of LTPA. The former athletes without blood pressure-lowering medication had significantly lower SBP than the controls [139.2 mmHg (SD 18.7) vs. 144.2 mmHg (SD 19.5)] (P = 0.027). CONCLUSION: A former career as an elite athlete seems to be associated with a lower prevalence of hypertension in later life. The volume of current LTPA was inversely related to prevalence of hypertension. PMID- 26136065 TI - Reliability of oscillometric central blood pressure and wave reflection readings: effects of posture and fasting. AB - OBJECTIVE: Oscillometric pulse wave analysis devices have recently emerged, presenting suitable options for investigating central hemodynamic properties in clinical practice. This study sought to examine whether the between-day reliability of central SBP (cSBP) and systemic arterial wave reflection (augmentation index, AIx) readings exceed the criterion for acceptable reliability or are affected by posture (supine and seated) and fasting state. METHODS: Twenty healthy adults (50% female, 27.9 years, 24.2 kg/m) were tested on six different mornings: 3 days fasted and 3 days nonfasted. On each occasion, participants were tested in supine and seated postures. Oscillometric pressure waveforms were recorded on left upper arm. RESULTS: For cSBP, there was nonsignificant main effect for fasting state (P = 0.819) but there was a main effect for posture (P = 0.002). Conversely, for AIx, there was nonsignificant main effect for posture (P = 0.537) but there was a large main effect for fasting state (P = < 0.001). The criterion intraclass correlation coefficient value of 0.75 was exceeded for both variables when participants were assessed under the combined supine-fasted condition. For cSBP, the reliability coefficient was lowest (best) when supine fasted (6.8 mmHg) and greatest (worst) when seated nonfasted (8.6 mmHg). For AIx, the reliability coefficient was lower for the supine (11.4-11.7%) compared with the seated (14.0-15.2%) posture. CONCLUSION: Findings from this study suggest that oscillometric assessments of central hemodynamic variables exceed the criterion for acceptable reliability and are most reliable when participants are evaluated while supine and fasted. PMID- 26136066 TI - Higher levels of von Willebrand factor in patients with syncope due to orthostatic hypotension. AB - OBJECTIVES: Orthostatic hypotension has been linked with increased mortality and cardiovascular morbidity; however, the underlying mechanisms are still unknown. The aim of the study was to assess markers of coagulability in patients with and without orthostatic hypotension who suffered transient loss of consciousness. METHODS: A total of 233 consecutive patients more than 15 years old, with unexplained transient loss of consciousness, underwent head-up tilt test (HUT, Italian protocol). Blood samples were collected during supine rest before and at 3 min of 70 degrees HUT for determination of fibrinogen, von Willebrand factor antigen (vWF:Ag) and activity (vWF:GP1bA), factor VIII (FVIII:C), lupus anticoagulant, and functional activated protein C-resistance. Orthostatic hypotension was defined as persistent decrease in SBP and/or DBP of more than 20/10 mmHg or SBP lower than 90 mmHg during passive HUT. RESULTS: One hundred and seventy-eight patients (81 men, 45.5%) not treated with vitamin-K antagonists were analyzed. Those with orthostatic hypotension (n = 49) were older [61 +/- 18 vs. 47 +/- 21 years (mean +/- SD), P < 0.001], had increased FVIII: C-supine (1.2 +/- 0.39 vs. 1.0 +/- 0.35, P = 0.001), FVIII:C-standing (1.2 +/- 0.36 vs. 1.0 +/- 0.34, P = 0.001), vWF:Ag-supine (1.5 +/- 0.66 vs. 1.1 +/- 0.44, P < 0.001), vWF:Ag-standing (1.5 +/- 0.67 vs. 1.1 +/- 0.46, P < 0.001), vWF:GP1bA-supine (1.5 +/- 0.73 vs. 1.1 +/- 0.42, P < 0.001), vWF:GP1bA-standing (1.5 +/- 0.75 vs. 1.1 +/- 0.42 P < 0.001), fibrinogen-standing (2.9 +/- 0.53 vs. 2.7 +/- 0.61, P = 0.03) but not fibrinogen-supine (2.8 +/- 0.54 vs. 2.7 +/- 0.61, P = 0.078) compared with patients without orthostatic hypotension. However, after adjustment for age, sex, and comorbidity, only vWF:Ag and vWF:GP1bA levels remained significantly increased in orthostatic hypotension patients. CONCLUSION: Concentration of vWF is elevated in patients with orthostatic hypotension who suffered a syncopal event. This observation may be helpful in understanding the increased risk of cardiovascular events in orthostatic hypotension. PMID- 26136067 TI - Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists. AB - OBJECTIVE: Endogenous cardiotonic steroids, including marinobufagenin (MBG), stimulate vascular synthesis of collagen. Because mineralocorticoid antagonists competitively antagonize effect of cardiotonic steroids on the Na/K-ATPase, we hypothesized that spironolactone would reverse the profibrotic effects of MBG. METHODS: Experiment 1: Explants of thoracic aortae and aortic vascular smooth muscle cells from Wistar rats were cultured for 24 h in the presence of vehicle or MBG (100 nmol/l) with or without canrenone (10 MUmol/l), an active metabolite of spironolactone. Experiment 2: In 16 patients (56 +/- 2 years) with resistant hypertension on a combined (lisinopril/amlodipine/hydrochlorothiazide) therapy, we determined arterial pressure, pulse wave velocity, plasma MBG, and erythrocyte Na/K-ATPase before and 6 months after addition of placebo (n = 8) or spironolactone (50 mg/day; n = 8) to the therapy. RESULTS: In rat aortic explants and in vascular smooth muscle cells, pretreatment with MBG resulted in a two-fold rise in collagen-1, and a marked reduction in the sensitivity of the aortic rings to the vasorelaxant effect of sodium nitroprusside following endothelin-1-induced constriction (EC50 = 480 +/- 67 vs. 23 +/- 3 nmol/l in vehicle-treated rings; P < 0.01). Canrenone blocked effects of MBG on collagen synthesis and restored sensitivity of vascular rings to sodium nitroprusside (EC50 = 17 +/- 1 nmol/l). Resistant hypertension patients exhibited elevated plasma MBG (0.42 +/- 0.07 vs. 0.24 +/- 0.03 nmol/l; P = 0.01) and reduced Na/K-ATPase activity (1.9 +/- 0.15 vs. 2.8 +/- 0.2 MUmol Pi/ml per h, P < 0.01) vs. seven healthy individuals. Six month administration of spironolactone, unlike placebo treatment, was associated with a decrease in pulse wave velocity and arterial pressure, and with restoration of Na/K-ATPase activity in the presence of unchanged MBG levels. CONCLUSION: MBG-induced vascular fibrosis is a likely target for spironolactone. PMID- 26136068 TI - Elevating circulation chemerin level is associated with endothelial dysfunction and early atherosclerotic changes in essential hypertensive patients. AB - OBJECTIVES: Chemerin is a new adipokine elevated in states of obesity and metabolic syndromes. In this study, we investigated the association of increased chemerin on endothelial function, arterial stiffness and early atherosclerosis in essential hypertensive patients. METHODS: Three hundred and sixty-seven newly diagnosed essential hypertensive patients were enrolled. Anthropometric measurements and plasma parameters were examined, including BMI, waist circumference, glucose, serum insulin, lipid profiles, chemerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and interleukin-4. Vascular health was assessed with brachial flow-mediated dilatation (FMD), brachial-ankle pulse wave velocity (baPWV), and carotid intima-media thickness (IMT). RESULTS: In hypertensive patients, plasma chemerin levels were higher in women than in men (P < 0.05). In univariate analysis, the plasma chemerin level was positively correlated with baPWV (men: r = 0.58, P < 0.01; women: r = 0.51, P < 0.01) and carotid IMT (men: r = 0.17, P = 0.01; women: r = 0.20, P = 0.01), and inversely correlated with FMD (men: r = -0.54, P < 0.01; women: r = -0.44, P < 0.01). The associations for FMD and baPWV, but not IMT, remained significant in multivariable models adjusted for age, sex, glucose homeostasis, lipid profiles, inflammation markers and adipokines. More importantly, logistic regression analysis revealed that high chemerin level was an independent predictor of impaired endothelial function (FMD odds ratio 1.58, 95% confidence interval 1.28 3.30, P = 0.03) and increased arterial stiffness (baPWV odds ratio 3.75, 95% confidence interval 1.36-5.28, P < 0.01), even after adjustment for metabolic variables, inflammatory markers and adipokines. CONCLUSION: Chemerin levels were independently associated with the index of arterial function and early atherosclerosis in essential hypertension. PMID- 26136069 TI - Association between serum uric acid, aortic, carotid and femoral stiffness among adults aged 40-75 years without and with type 2 diabetes mellitus: The Maastricht Study. AB - OBJECTIVE: Arterial stiffness may be a mechanism to explain the association between uric acid and cardiovascular disease. We aimed to analyse associations between serum uric acid and regional and local arterial stiffness, and assess potential differences related to sex and glucose metabolism status. METHODS: A cross-sectional study was performed in 614 adults [52.6% men; mean age 58.7 +/- 8.5 years; 23.2% type 2 diabetes mellitus (by design)] from The Maastricht Study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), distensibility, and compliance coefficient of the carotid and femoral artery, and carotid artery Young's elastic modulus. RESULTS: Higher uric acid (per SD of 74 MUmol/l) was associated with greater stiffness indicated by a significantly higher cfPWV [beta = 0.216 (95% confidence interval 0.061, 0.372); P = 0.006] and lower carotid distensibility coefficient [beta = -0.633 (95% confidence interval 1.099, -0.166); P = 0.008] after adjustment for sex, age, and glucose metabolism status. Associations lost significance after adjusting for mean arterial pressure, BMI, waist, smoking status, heart rate, total : high-density lipoprotein cholesterol ratio, triglycerides, estimated glomerular filtration rate, use of lipid-lowering, antihypertensive, and diabetes medication, and use of secondary uricosurics. No associations were found between uric acid and carotid compliance coefficient, carotid Young's elastic modulus, or stiffness of the femoral artery. A significant interaction (P < 0.10) with glucose metabolism status was found for cfPWV. However, none of the stratified associations were significant. There was no interaction with sex. CONCLUSION: Uric acid was not significantly associated with stiffness of the aorta, or the carotid or femoral artery among adults aged 40-75 years without and with type 2 diabetes mellitus. PMID- 26136070 TI - Intermedin1-53 protects against cardiac hypertrophy by inhibiting endoplasmic reticulum stress via activating AMP-activated protein kinase. AB - OBJECTIVE: Intermedin (IMD), a novel member of the calcitonin/calcitonin gene related peptide family, is involved in maintaining circulatory homeostasis and is a protective factor of heart and vessel. Here, we investigated the effects of IMD on cardiac hypertrophy in vivo and in vitro and explored the mechanisms involved. METHODS AND RESULTS: IMD1-53 (100 ng/kg/h) was systemically administered to rats with cardiac hypertrophy induced by abdominal aortic constriction (AAC) by a mini osmotic pump the next day after surgery continuously for 4 weeks. The AAC-treated rats before IMD infusion showed increased IMD content and expression of its receptors in the hearts. In-vivo administration of IMD1-53 greatly attenuated the cardiac hypertrophy as shown by heart weight to body weight ratio (HW/BW), haemodynamics, echocardiography, histological analyses and expression of hypertrophic markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) induced by AAC. IMD1-53 treatment significantly reduced the myocardial protein expression of endoplasmic reticulum stress (ERS) markers such as glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12, whereas the protein level of phosphorylated AMP-activated protein kinase (p-AMPK) was upregulated with IMD1-53 treatment, which was further confirmed in cultured cardiomyocytes. Concurrently, cardiomyocyte apoptosis in vivo and in vitro was ameliorated by IMD1-53 treatment. The inhibitory effects of IMD1-53 on ERS and apoptosis were eliminated on pretreatment with compound C, an AMPK inhibitor. CONCLUSION: IMD1-53 could exert its cardioprotective effect on cardiac hypertrophy by inhibiting myocardial ERS and apoptosis, possibly via activation of AMPK signalling. PMID- 26136071 TI - The dynamics of hypertension prevalence, awareness, treatment, control and associated factors in Chinese adults: results from CHNS 1991-2011. AB - OBJECTIVES: To analyze the trends in blood pressure (BP), and the prevalence, awareness, treatment and control of hypertension and associated factors in Chinese adults from 1991 to 2011. METHODS: On the basis of the longitudinal data of China Health and Nutrition Survey, 75 526 records of 24 410 adults were selected according to the eligibility criteria. The age-standardized levels of SBP, DBP, prevalence, awareness, treatment and control of hypertension were calculated by sex and age group within each year. Generalized estimating equation was employed to investigate the associations between demographic factors and status of hypertension, awareness, treatment and control. RESULTS: From 1991 to 2011, the BP level elevated (SBP 120.0-124.5 mmHg, DBP 76.7-79.3 mmHg) and the prevalence of hypertension increased from 23.4 to 28.6%. The increasing levels of BP and hypertension prevalence were more apparent among men and older patients. The rates of hypertension awareness, treatment and control also increased while kept at low levels. Factors such as age, sex, smoking habit, drinking habit, household income, health insurance, BMI, residential region, marital status, educational level and nationality were significantly associated with the status of hypertension, awareness, treatment and control. CONCLUSION: The BP level and hypertension prevalence have increased among Chinese adults in recent years. However, levels of hypertension awareness, treatment and control were quite low. To reduce the disease burden of the hypertension, improvements in health education programs, detection and treatment strategies are warranted. PMID- 26136072 TI - Cefoxitin as a carbapenem-sparing antibiotic for infections caused by extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. AB - BACKGROUND: Cefoxitin has demonstrated in vitro resistance to hydrolysis by extended-spectrum beta-lactamases. METHODS: We evaluated the microbiological and clinical efficacy of cefoxitin in 33 patients treated for an infection related to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). Clinical and microbiological outcomes were assessed from the initiation of cefoxitin therapy to the latest information available in the patient's medical file. RESULTS: The 33 patients were mainly males (n = 26), aged 70 years (median, minimum-maximum: 23-93) and main sites of infection were urinary (n = 23) and catheter-related bloodstream infections (n = 4). Escherichia coli and Klebsiella pneumoniae were isolated in 19 and 14 subjects, respectively. The clinical outcome was favorable in 30 of 33 patients in the first 48 h after the start of cefoxitin, and in 20 (of 24 evaluable) at the end of follow-up. Six microbiological failures were documented and resistance to cefoxitin emerged in two strains of K. pneumoniae. CONCLUSIONS: Cefoxitin could be considered as a carbapenem-sparing antibiotic for some ESBL-E infections, preferentially those related to E. coli. PMID- 26136073 TI - Non-Muscle Myosin II Isoforms Have Different Functions in Matrix Rearrangement by MDA-MB-231 Cells. AB - The role of a stiffening extra-cellular matrix (ECM) in cancer progression is documented but poorly understood. Here we use a conditioning protocol to test the role of nonmuscle myosin II isoforms in cell mediated ECM arrangement using collagen constructs seeded with breast cancer cells expressing shRNA targeted to either the IIA or IIB heavy chain isoform. While there are several methods available to measure changes in the biophysical characteristics of the ECM, we wanted to use a method which allows for the measurement of global stiffness changes as well as a dynamic response from the sample over time. The conditioning protocol used allows the direct measurement of ECM stiffness. Using various treatments, it is possible to determine the contribution of various construct and cellular components to the overall construct stiffness. Using this assay, we show that both the IIA and IIB isoforms are necessary for efficient matrix remodeling by MDA-MB-231 breast cancer cells, as loss of either isoform changes the stiffness of the collagen constructs as measured using our conditioning protocol. Constructs containing only collagen had an elastic modulus of 0.40 Pascals (Pa), parental MDA-MB-231 constructs had an elastic modulus of 9.22 Pa, while IIA and IIB KD constructs had moduli of 3.42 and 7.20 Pa, respectively. We also calculated the cell and matrix contributions to the overall sample elastic modulus. Loss of either myosin isoform resulted in decreased cell stiffness, as well as a decrease in the stiffness of the cell-altered collagen matrices. While the total construct modulus for the IIB KD cells was lower than that of the parental cells, the IIB KD cell-altered matrices actually had a higher elastic modulus than the parental cell-altered matrices (4.73 versus 4.38 Pa). These results indicate that the IIA and IIB heavy chains play distinct and non redundant roles in matrix remodeling. PMID- 26136074 TI - Identification of thiostrepton as a novel therapeutic agent that targets human colon cancer stem cells. AB - Accumulating evidence shows that colorectal cancer stem cells (CRSCs) are largely responsible for the metastasis and relapse of colorectal cancer (CRC) after therapy. Hence, identifying new agents that specifically target CRSCs would help improve the effectiveness of current CRC therapies. To accelerate identification of agents targeting CRSCs, the Connectivity Map (CMap) approach was used. Among the top-ranked candidates, thiostrepton, a thiazole antibiotic, was selected for further investigation because of its known tumoricidal activity. Thiostrepton could selectively induce apoptosis in CRSC subpopulations in both parental HCT-15 and HT-29 human CRC lines as well as in EMT and chemoresistant clones derived from them. Further, we investigated its inhibitory effects on the sphere- and colony-forming capabilities of the aforementioned CRC lines. The in vitro inhibition of sphere and colony formation was associated with downregulation of various modulators of the stem cell phenotype. The combination of thiostrepton and oxaliplatin eradicated both CD44(+) HCT-15 and HT-29 cells more efficiently than either drug alone. FoxM1, an oncogenic transcription factor, was identified as a critical positive modulator of stemness and as the main target of thiostrepton in the CRC lines. This is the first report showing the selective killing of CRSCs by thiostrepton, which has been proposed to be a promising anti neoplastic agent. On the basis of its synergism with oxaliplatin in killing CRSCs in vitro, if this activity is confirmed in vivo, thiostrepton may be a promising agent to be used clinically in combination with current chemotherapies to improve the efficacy of these regimens. PMID- 26136075 TI - LincHOTAIR epigenetically silences miR34a by binding to PRC2 to promote the epithelial-to-mesenchymal transition in human gastric cancer. AB - lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients. PMID- 26136076 TI - Disruption of cellular homeostasis induces organelle stress and triggers apoptosis like cell-death pathways in malaria parasite. AB - A regulated protein turnover machinery in the cell is essential for effective cellular homeostasis; any interference with this system induces cellular stress and alters the normal functioning of proteins important for cell survival. In this study, we show that persistent cellular stress and organelle dysfunction because of disruption of cellular homeostasis in human malaria parasite Plasmodium falciparum, leads to apoptosis-like cell death. Quantitative global proteomic analysis of the stressed parasites before onset of cell death, showed upregulation of a number of proteins involved in cellular homeostasis; protein network analyses identified upregulated metabolic pathways that may be associated with stress tolerance and pro-survival mechanism. However, persistent stress on parasites cause structural abnormalities in endoplasmic reticulum and mitochondria, subsequently a cascade of reactions are initiated in parasites including rise in cytosolic calcium levels, loss of mitochondrial membrane potential and activation of VAD-FMK-binding proteases. We further show that activation of VAD-FMK-binding proteases in the parasites leads to degradation of phylogenetically conserved protein, TSN (Tudor staphylococcal nuclease), a known target of metacaspases, as well as degradation of other components of spliceosomal complex. Loss of spliceosomal machinery impairs the mRNA splicing, leading to accumulation of unprocessed RNAs in the parasite and thus dysregulate vital cellular functions, which in turn leads to execution of apoptosis-like cell death. Our results establish one of the possible mechanisms of instigation of cell death by organelle stress in Plasmodium. PMID- 26136079 TI - Electrochemical reduction of aromatic ketones in 1-butyl-3-methylimidazolium based ionic liquids in the presence of carbon dioxide: the influence of the ketone substituent and the ionic liquid anion on bulk electrolysis product distribution. AB - Electrochemical reduction of aromatic ketones, including acetophenone, benzophenone and 4-phenylbenzophenone, has been undertaken in 1-butyl-3 methylimidazolium-based ionic liquids containing tetrafluoroborate ([BF4](-)), trifluoromethanesulfonate ([TfO](-)) and tris(pentafluoroethyl)trifluorophosphate ([FAP](-)) anions in the presence of carbon dioxide in order to investigate the ketone substituent effect and the influence of the acidic proton on the imidazolium cation (C2-H) on bulk electrolysis product distribution. For acetophenone, the minor products were dimers (<10%) in all ionic liquids, which are the result of acetophenone radical anion coupling. For benzophenone and 4 phenylbenzophenone, no dimers were formed due to steric hindrance. In these cases, even though carboxylic acids were obtained, the main products generated were alcohols (>50%) derived from proton coupled electron transfer reactions involving the electrogenerated radical anions and C2-H. In the cases of both acetophenone and benzophenone, the product distribution is essentially independent of the ionic liquid anion. By contrast, 4-phenylbenzophenone shows a product distribution that is dependent on the ionic liquid anion. Higher yields of carboxylic acids (~40%) are obtained with [TfO](-) and [FAP](-) anions because in these ionic liquids the C2-H is less acidic, making the formation of alcohol less favourable. In comparison with benzophenone, a higher yield of carboxylic acid (>30% versus ~15%) was obtained with 4-phenylbenzophenone in all ionic liquids due to the weaker basicity of 4-phenylbenzophenone radical anion. PMID- 26136077 TI - Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain. AB - Survival and proliferation of cancer cells are often associated with hyperactivity of the serine/threonine kinase, Akt. Herein, we show that prosurvival activity of Akt can be converted into prodeath activity by embedding an Akt recognition sequence in the apoptogenic BH3 domain of human BIM. The recognition sequence was created by introducing two mutations, I155R and E158S, into the core region of the BIM BH3 domain. Although a 21-mer BIM BH3 peptide containing these two mutations bound weakly to BCL-XL and BCL-2, this peptide with phosphorylation of Ser158 bound to these proteins with a dissociation constant of <10 nM. The crystal structure of the phosphorylated peptide bound to BCL-XL revealed that the phospho-Ser158 makes favorable interactions with two BCL XL residues, which cannot be formed with unphosphorylated Ser158. Remarkably, the designed peptide showed a cytotoxic effect on PTEN-null PC3 tumor cells whose Akt activity is aberrantly high. The cell-killing activity disappeared when the cellular Akt activity was lowered by ectopic PTEN expression. Thus, these results lay a foundation for developing a peptide or protein agent that is dormant in normal cells but is transformed into a potent apoptogenic molecule upon phosphorylation by hyperactivity of Akt in cancer cells. PMID- 26136078 TI - Metabolic stress induces a Wnt-dependent cancer stem cell-like state transition. AB - Reciprocal interactions between cancer cells and the tumor microenvironment drive multiple clinically significant behaviors including dormancy, invasion, and metastasis as well as therapy resistance. These microenvironment-dependent phenotypes share typical characteristics with cancer stem cells (CSC). However, it is poorly understood how metabolic stress in the confined tumor microenvironment contributes to the emergence and maintenance of CSC-like phenotypes. Here, we demonstrate that chronic metabolic stress (CMS) in a long term nutrient deprivation induces a Wnt-dependent phenoconversion of non-stem cancer cells toward stem-like state and this is reflected in the transcriptome analysis. Addition of Wnt3a as well as transfection of dominant-negative Tcf4 establishes an obligatory role for the Wnt pathway in the acquisition of CSC-like characteristics in response to metabolic stress. Furthermore, systematic characterization for multiple single cell-derived clones and negative enrichment of CD44+/ESA+ stem-like cancer cells, all of which recapitulate stem-like cancer characteristics, suggest stochastic adaptation rather than selection of pre existing subclones. Finally, CMS in the tumor microenvironment can drive a CSC like phenoconversion of non-stem cancer cells through stochastic state transition dependent on the Wnt pathway. These findings contribute to an understanding of the metabolic stress-driven dynamic transition of non-stem cancer cells to a stem like state in the tumor metabolic microenvironment. PMID- 26136080 TI - Fatal multifocal Pasteurella multocida infection: a case report. AB - BACKGROUND: In humans, Pasteurella multocida infections are usually limited to the soft tissues surrounding a lesion. However, P. multocida can also cause systemic infections (such as pneumonia, lung abscess, peritonitis, endocarditis, meningitis and sepsis)-especially in patients with other underlying medical conditions. CASE PRESENTATION: We report on a case of fulminant P. multocida bacteremia at several sites (soft tissues, endocarditis and joints) on a white European man. Despite surgery and intensive medical care, the patient died. CONCLUSIONS: The present case emphasizes the importance of appropriate initial treatment of skin wounds. Patients at risk should be aware of the possible consequences of being bitten, scratched or licked by their pet. PMID- 26136081 TI - Mortality from heart failure, acute myocardial infarction and other ischaemic heart disease in England and Oxford: a trend study of multiple-cause-coded death certification. AB - BACKGROUND: Age-standardised death rates from acute myocardial infarction (AMI) and ischaemic heart disease (IHD) have been declining in most developed countries. However, the magnitude of such reductions and how they impact on death from heart failure are less certain. We sought to assess and compare temporal trends in mortality from heart failure, AMI and non-AMI IHD over a 30-year period in England. METHODS: We analysed death registration data for multiple-cause-coded mortality for all deaths in people aged 35 years and over in England from 1995 to 2010, population 52 million, and in a regional population (Oxford region) from 1981 to 2010, population 2.5 million, for which data on all causes of death were available. RESULTS: Considering all ages and both sexes combined, during the 30 year observation period, age-standardised and sex-standardised mortality rates based on all certified causes of death declined by 60% for heart failure, 80% for AMI and 46% for non-AMI IHD. These longer term trends observed in the Oxford region were consistent with those for the whole of England from 1995 to 2010, with no evidence of a plateau in recent years. Although proportional reductions in rates differed by age and sex, even in those aged 85 years or more, there were substantial reductions in mortality rates in the all-England data set (50%, 66% and 20% for heart failure, AMI and non-AMI IHD, respectively). CONCLUSIONS: This study shows large and sustained reductions in age-specific and sex-specific and standardised death rates from heart failure, as well as from AMI and non-AMI IHD, over a 30-year period in England. PMID- 26136083 TI - Developmental inhibition and DNA damage of Helicoverpa armigera Hubner (Lepidoptera: Noctuidae) by gamma radiation. AB - PURPOSE: Gamma radiation on Helicoverpa armigera Hubner was performed to assess developmental inhibition and to identify a potential quarantine treatment dose of the radiation. MATERIALS AND METHODS: Gamma radiation ((60)Co) treatment at different doses of 50, 100, 200, 300, and 400 Gy was carried out with egg, larvae, pupae and adults of H. armigera. RESULTS: Gamma radiation induced developmental inhibition of all stages of H. armigera. The effective dose values required for inhibition 99% (ED(99)) of hatching, pupation and adult emergence from the irradiated eggs were 550.7, 324.9 and 136.4 Gy, respectively. ED(99) values for inhibition of the larvae to adult emergence was 200.0 Gy. Irradiation on pupae could not completely inhibit adult emergence even at 400 Gy. ED(99) value for inhibition of F(1) egg hatchability from the irradiated adults was estimated to be 229.5 Gy. CONCLUSIONS: This study suggests that gamma radiation is a possible alternative to phytosanitary treatments. Irradiation treatment with minimum dose of 200 Gy can be suggested as optimum dose for larval treatment in quarantine. PMID- 26136082 TI - Spatial social polarisation: using the Index of Concentration at the Extremes jointly for income and race/ethnicity to analyse risk of hypertension. AB - BACKGROUND: Growing spatial social and economic polarisation may be an important societal determinant of health, but only a few studies have used the recently developed Index of Concentration at the Extremes (ICE) to analyse the impact of joint concentrations of privilege and privation on health outcomes. We explore use of the ICE to investigate risk of hypertension in an urban, multiracial/ethnic, and predominantly working-class study population of US adults. METHODS: We generated novel ICE measures at the census tract level that jointly assess extreme concentrations of both income and racial/ethnic composition. We then linked the ICE measures to data from two observational, cross-sectional studies conducted in the Boston metropolitan area (2003-2004; 2008-2010; N=2145). RESULTS: The ICE measure for extreme concentrations of white compared with black residents was independently associated with lower odds of hypertension (OR=0.76; 95% CI 0.62 to 0.93), controlling for race/ethnicity, age, gender, smoking, body mass index, household income, education and self-reported exposure to racial discrimination. Even stronger associations were observed for the ICE measures that compared concentrations of high-income white residents versus low-income residents of colour (OR=0.61; 95% CI 0.40 to 0.96) and high income white versus low-income black residents (OR=0.48; 95% CI 0.29 to 0.81). CONCLUSIONS: Results suggest public health studies should explore the joint impact of racial/ethnic and economic spatial polarisation on population health. PMID- 26136084 TI - Assessing patient characteristics and radiation-induced non-targeted effects in vivo for high dose-rate (HDR) brachytherapy. AB - PURPOSE: To test whether blood, urine, and tissue based colony-forming assays are a useful clinical detection tool for assessing fractionated treatment responses and non-targeted radiation effects in bystander cells. MATERIALS AND METHODS: To assess patients' responses to radiation treatments, blood serum, urine, and an esophagus explant-based in vivo colony-forming assay were used from oesophageal carcinoma patients. These patients underwent three fractions of high dose rate (HDR) intraluminal brachytherapy (ILBT). RESULTS: Human keratinocyte reporters exposed to blood sera taken after the third fraction of brachytherapy had a significant increase in cloning efficiency compared to baseline samples (p < 0.001). Such results may suggest an induced radioresistance response in bystander cells. The data also revealed a clear inverse dose-rate effect during late treatment fractions for the blood sera data only. Patient characteristics such as gender had no statistically significant effect (p > 0.05). Large variability was observed among the patients' tissue samples, these colony-forming assays showed no significant changes throughout fractionated brachytherapy (p > 0.05). CONCLUSION: Large inter-patient variability was found in the urine and tissue based assays, so these techniques were discontinued. However, the simple blood based assay had much less variability. This technique may have future applications as a biological dosimeter to predict treatment outcome and assess non-targeted radiation effects. PMID- 26136085 TI - Formation and repair of clustered damaged DNA sites in high LET irradiated cells. AB - PURPOSE: Radiation with high linear energy transfer (LET) produces clustering of DNA double-strand breaks (DSB) as well as non-DSB lesions. Heat-labile sites (HLS) are non-DSB lesions in irradiated cells that may convert into DSB at elevated temperature during preparation of naked DNA for electrophoretic assays and here we studied the initial formation and repair of these clustered damaged sites after irradiation with high LET ions. MATERIALS AND METHODS: Induction and repair of DSB were studied in normal human skin fibroblast (GM5758) after irradiation with accelerated carbon and nitrogen ions at an LET of 125 eV/nm. DNA fragmentation was analyzed by pulsed-field gel electrophoresis (PFGE) and by varying the lysis condition we could differentiate between prompt DSB and heat released DSB. RESULTS: Before repair (t = 0 h), the 125 eV/nm ions produced a significant fraction of heat-released DSB, which appeared clustered on DNA fragments with sizes of 1 Mbp or less. These heat-released DSB increased the total number of DSB by 30-40%. This increase is similar to what has been found in low-LET irradiated cells, suggesting that the relative biological effectiveness (RBE) for DSB induction will not be largely affected by the lysis temperature. After 1-2 hours repair, a large fraction of DSB was still unrejoined but there was essentially no heat-released DSB present. CONCLUSIONS: These results suggest that high LET radiation, as low LET gamma radiation, induces a significant fraction of heat-labile sites which can be converted into DSB, and these heat released DSB may affect both induction yields and estimates of repair. PMID- 26136086 TI - High dose rate and flattening filter free irradiation can be safely implemented in clinical practice. AB - PURPOSE: We hypothesize that flattening filter free (FFF) high dose rate irradiation will decrease cell survival in normal and cancer cells with more pronounced effects in DNA repair deficient cells. Additionally, we hypothesize that removal of the flattening filter will result in an enhanced relative biological effectiveness independent of the dose rate. MATERIALS AND METHODS: Clonogenic survival was assessed after exposure to dose rates of 4 or 24 Gy/min (FFF 10 megavolt [MV] photon beam) using a Varian TrueBeam accelerator. Additionally, cells were exposed to 4 Gy/min with or without flattening filter. Relative biological effectiveness estimations were performed comparing the different beam photon spectra. RESULTS: Cell survival in tumor and normal cell lines was not influenced by high dose rate irradiation. The intrinsic radiation sensitivity of DNA repair deficient cells was not affected by high dose rate compared to normal dose rate. Furthermore, the relative biological effectiveness was not significantly different from unity in any of the cell lines for both FFF and conventional flattened beam exposures. CONCLUSIONS: High dose rate irradiation did not affect long-term survival and DNA repair for cell lines of different tissues. This suggests that high dose rate does not influence treatment outcome or treatment toxicity and could be safely implemented in clinical routine. PMID- 26136087 TI - 2.1 GHz electromagnetic field does not change contractility and intracellular Ca2+ transients but decreases beta-adrenergic responsiveness through nitric oxide signaling in rat ventricular myocytes. AB - PURPOSE: Due to the increasing use of wireless technology in developing countries, particularly mobile phones, the influence of electromagnetic fields (EMF) on biologic systems has become the subject of an intense debate. Therefore, in this study we investigated the effect of 2.1 GHz EMF on contractility and beta adrenergic (beta-AR) responsiveness of ventricular myocytes. MATERIALS AND METHODS: Rats were randomized to the following groups: Sham rats (SHAM) and rats exposed to 2.1 GHz EMF for 2 h/day for 10 weeks (EM-10). Sarcomere shortening and Ca(2+) transients were recorded in isolated myocytes loaded with Fura2-AM and electrically stimulated at 1 Hz, while L-type Ca(2+) currents (I(CaL)) were measured using whole-cell patch clamping at 36 +/- 1 degrees C. Cardiac nitric oxide (NO) levels were measured in tissue samples using a colorimetric assay kit. RESULTS: Fractional shortening and amplitude of the matched Ca(2+) transients were not changed in EM-10 rats. Although the isoproterenol-induced (10(-6) M) I(CaL) response was reduced in rats exposed to EMF, basal I(CaL) density in myocytes was similar between the two groups (p < 0.01). Moreover, EMF exposure led to a significant increase in nitric oxide levels in rat heart (p < 0.02). CONCLUSIONS: Long-term exposure to 2.1 GHz EMF decreases beta-AR responsiveness of ventricular myocytes through NO signaling. PMID- 26136088 TI - Frequency-dependent effects of sequenced pulsed magnetic field on experimental diabetic neuropathy. AB - PURPOSE: Pulsed magnetic field (PMF) as an important non- invasive alternative therapeutic option has been investigated in several pre-clinical and clinical studies. We also hypothesized that sequenced PMF formed with different frequencies can modulate the diabetes-induced neuropathic signs differently. MATERIALS AND METHODS: Therapeutic actions of sequenced PMF including 1, 5, 1, 5 Hz (low (L)-PMF) or 30, 40, 30, 40 Hz (high (H)-PMF) were examined on improving signs and symptoms of diabetic neuropathic pain in the streptozotocin-induced diabetic rat models by measuring nociceptive parameters such as hyperalgesia and allodynia, and various cytokine levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1 beta, IL-6 and IL-10) of spinal cord and sciatic nerve tissues. RESULTS: Ameliorating potential of L-PMF application on signs of diabetes is significantly higher than those of H-PMF. L-PMF partially attenuated the diabetes-induced increase in the blood glucose level, enhanced the decreased thresholds and latency during the experiments. Diabetes enhanced the pro inflammatory cytokine, TNF-alpha, IL-1 beta and IL-6, levels in spinal cord and sciatic nerve of rats. L-PMF treatments to diabetic rats decreased these, but enhanced the production of anti-inflammatory cytokine, IL-10. CONCLUSIONS: The present results demonstrated that sequenced L-PMF treatment can relieve neuropathic signs of diabetes in rats. Anti-hyperglycemic, anti-allodynic and anti-hyperalgesic effects of L-PMF treatment can be closely correlated with each other. Furthermore, decreasing actions of L-PMF on pro-inflammatory/anti inflammatory cytokine ratio can suggest that the therapeutic potential of L-PMF in diabetes induced neuropathy may involve the regulation of the neuroinflammatory/neuroimmune processes. PMID- 26136089 TI - Analysis of immune cell populations and cytokine profiles in murine splenocytes exposed to whole-body low-dose irradiation. AB - PURPOSE: In contrast to high-dose therapeutic irradiation, definitive research detailing the physiological effects of low-dose irradiation is limited. Notably, the immunological response elicited after low-dose irradiation remains controversial. MATERIALS AND METHODS: Female C57BL/6 mice were whole- body irradiated with a single or three daily fractions up to a total dose of 0.1, 1, or 10 cGy. Blood and spleen were harvested 2, 7 and 14 days after irradiation. RESULTS: The splenic CD4(+) T cell subpopulations were temporarily increased at 2 days after single or fractionated irradiation, whereas the percentage of dendritic cells (DC) and macrophages was decreased. Whereas CD8(+) T cell populations were decreased in single-dose irradiated mice at day 7, early and sustained reduction of CD8(+) T cell numbers was observed in fractionated- dose irradiated mice from day 2 until day 14. In addition, single-dose irradiation resulted in a Th1 cytokine expression profile, whereas fractionated-dose irradiation drove a Th2 shift. Additionally, increased expression of immune related factors was observed at early time-points with single-dose irradiation, in contrast to the dose-independent induction following fractionated-dose irradiation. CONCLUSIONS: Our results demonstrate that low-dose irradiation modulates the immune response in mice, where the sensitivity and kinetics of the induced response vary according to the dosing method. PMID- 26136090 TI - Palladium-catalyzed asymmetric intermolecular Mizoroki-Heck reaction for construction of a chiral quaternary carbon center. AB - Palladium-catalyzed asymmetric intermolecular Mizoroki-Heck reaction for the construction of a chiral quaternary carbon center is developed, affording 2,2 disubstituted 2,5-dihydrofurans in high yield with excellent enantioselectivity. The products are easily converted into the corresponding butenolides with retention of enantioselectivity. PMID- 26136091 TI - Erratum to: A Comparative Assessment of Observational Medical Outcomes Partnership and Mini-Sentinel Common Data Models and Analytics: Implications for Active Drug Safety Surveillance. PMID- 26136101 TI - Postoperative Critical Care of the Adult Cardiac Surgical Patient: Part II: Procedure-Specific Considerations, Management of Complications, and Quality Improvement. AB - OBJECTIVES: The armamentarium of cardiac surgery continues to expand, and the cardiac intensivist must be familiar with a broad spectrum of procedures and their specific management concerns. In the conclusion of this two-part review, we will review procedure-specific concerns after cardiac surgery and the management of common complications. We also discuss performance improvement and outcome assurance. DATA SOURCE AND SYNTHESIS: Narrative review of relative English language peer-reviewed medical literature. CONCLUSIONS: Knowledge of procedure specific sequelae informs anticipation and prevention of many complications after cardiac surgery. Most complications after cardiac surgery fall into a limited number of categories. Familiarity with common complications combined with a structured approach to management facilitates response to even the most complicated postoperative situations. Standardized care and constant self examination are essential for programmatic improvement and consistent high quality care. PMID- 26136102 TI - Brief Versus Full Alcohol Use Disorders Identification Test in National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network Clinical Trials. AB - OBJECTIVES: Alcohol use disorders are common among patients admitted to an ICU, yet systematic screening is rarely performed. We sought to confirm the construct validity of the full Alcohol Use Disorders Identification Test and to evaluate the performance of the brief three-item Alcohol Use Disorders Identification Test C using the full Alcohol Use Disorders Identification Test as a proxy gold standard in a population of patients with a medical critical illness. DESIGN: Secondary analysis. SETTING: The acute respiratory distress syndrome network, a consortium of 12 university centers (44 hospitals) dedicated to conducting multicenter clinical trials in patients with acute respiratory distress syndrome. SUBJECTS: Patients meeting consensus criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,133 patients enrolled in one of three acute respiratory distress syndrome network studies, 1,037 (92%) had full Alcohol Use Disorders Identification Test data available. Of the included patients, 236 (23%) scored above the screening threshold for an alcohol use disorder on the full Alcohol Use Disorders Identification Test. Construct validity analysis of the full Alcohol Use Disorders Identification Test supported a three-factor model. Compared with the full Alcohol Use Disorders Identification Test, the Alcohol Use Disorders Identification Test -C had an area under the receiver operating characteristic curve of 0.99 for men and 0.98 for women. The optimal cutoff was 4 for both genders. At this cutoff, the Alcohol Use Disorders Identification Test -C had a sensitivity of 95% (95% CI, 92-98%) and specificity of 94% (95% CI, 92-96%) for men and sensitivity of 89% (95% CI, 82 96%) and specificity of 99% (95% CI, 98-100%) for women. CONCLUSIONS: Although a three-factor structure for the Alcohol Use Disorders Identification Test was confirmed in ICU patients with acute respiratory distress syndrome, the first three questions focusing on alcohol consumption provide information that is comparable with the full 10-item Alcohol Use Disorders Identification Test screening questionnaire. This study is limited by the lack of a true gold standard, and the performance of the Alcohol Use Disorders Identification Test -C is likely overestimated due to this limitation. PMID- 26136103 TI - Quantitative impact of direct, personal feedback on hand hygiene technique. AB - This study investigated the effectiveness of targeting hand hygiene technique using a new training device that provides objective, personal and quantitative feedback. One hundred and thirty-six healthcare workers in three Hungarian hospitals participated in a repetitive hand hygiene technique assessment study. Ultraviolet (UV)-labelled hand rub was used at each event, and digital images of the hands were subsequently taken under UV light. Immediate objective visual feedback was given to participants, showing missed areas on their hands. The rate of inadequate hand rubbing reduced from 50% to 15% (P < 0.001). However, maintenance of this reduced rate is likely to require continuous use of the electronic equipment. PMID- 26136104 TI - YCG063 inhibits Pseudomonas aeruginosa LPS-induced inflammation in human retinal pigment epithelial cells through the TLR2-mediated AKT/NF-kappaB pathway and ROS independent pathways. AB - YCG063 is known as an inhibitor of reactive oxygen species (ROS); however, its intracellular mechanisms of action remain poorly understood. In the present study, we investigated the effects of YCG063 on the inflammatory response of Pseudomonas aeruginosa lipopolysaccharide (PA-LPS)-stimulated human retinal pigment epithelial cells (RPE cells). Human adult RPE cells (ARPE-19) were stimulated with PA-LPS. We then investigated the LPS-induced expression of several inflammatory mediators, such as interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and intracellular adhesion molecule-1 (ICAM-1) in the ARPE-19 cells. We performed an enzyme-linked immunosorbent assay (ELISA), western blot analysis, electrophoretic mobility shift assay (EMSA) and fluorescence-activated cell sorting (FACS) to elucidate the mechanisms involved in the anti-inflammatory effects of YCG063 in the PA-LPS-stimulated cells. The results revealed that treatment with YCG063 significantly inhibited the levels of IL-6, IL-8, MCP-1 and ICAM-1 in the PA-LPS-stimulated ARPE-19 cells. YCG063 also markedly inhibited the phosphorylation of AKT in the PA-LPS-stimulated cells. In addition, the activation of nuclear factor-kappaB (NF-kappaB) was also attenuated folllowing treatment with YCG063. ROS were not generated in the PA-LPS-stimulated cells. In conclusion, our data indicate that YCG063 may prove to be a potential protective agent against inflammation, possibly through the downregulation of Toll-like receptor 2 (TLR2) and the AKT-dependent NF-kappaB activation pathway in PA-LPS-stimulated ARPE-19 cells. Furthermore, this anti-inflammatory activity occurred through ROS-independent signaling pathways. PMID- 26136105 TI - A novel deep photodynamic therapy modality combined with CT imaging established via X-ray stimulated silica-modified lanthanide scintillating nanoparticles. AB - Multifunctional LaF3:Tb scintillating nanoparticles (ScNPs) coated with homogenous layers of silica and subsequently tethered with RB covalently were elaborated. The nanoconjugates with a high colloidal stability and biocompatibility could generate a reasonable amount of (1)O2 through efficient energy transfer upon external illumination, which enables them to be potentially applied in diagnosis and photodynamic therapy for deep seated tumour. PMID- 26136106 TI - Oxo Ligand Substitution in a Cationic Uranyl Complex: Synergistic Interaction of an Electrophile and a Reductant. AB - Reaction of [U(VI)O2(dppmo)2(OTf)][OTf] (dppmo = Ph2P(O)CH2P(O)Ph2) with 4 equiv of Ph3SiOTf and 2 equiv of Cp2Co generates the U(IV) complex U(IV)(OTf)4(dppmo)2 (1), as a yellow-green crystalline solid in 83% yield, along with Ph3SiOSiPh3 and [Cp2Co][OTf]. This reaction proceeds via a U(IV) silyloxide intermediate, [U(IV)(OSiPh3)(dppmo)2(OTf)2][OTf] (2), which we have isolated and structurally characterized. Similarly, reaction of [U(VI)O2(TPPO)4][OTf]2 (TPPO = Ph3PO) with 6 equiv of Me3SiOTf and 2 equiv of Cp2Co generates the U(IV) complex, [Cp2Co][U(IV)(OTf)5(TPPO)2] (3), as a yellow-green crystalline solid in 76% yield, concomitant with formation of Me3SiOSiMe3, [Ph3POSiMe3][OTf], and [Cp2Co][OTf]. Complexes 1 and 3 have been fully characterized, including analysis by X-ray crystallography. The conversion of [U(VI)O2(dppmo)2(OTf)][OTf] and [U(VI)O2(TPPO)4][OTf]2 to complexes 1 and 3, respectively, represents rare examples of well-defined uranyl oxo ligand substitution. PMID- 26136107 TI - Intracranial EEG correlates of implicit relational inference within the hippocampus. AB - Drawing inferences from past experiences enables adaptive behavior in future situations. Inference has been shown to depend on hippocampal processes. Usually, inference is considered a deliberate and effortful mental act which happens during retrieval, and requires the focus of our awareness. Recent fMRI studies hint at the possibility that some forms of hippocampus-dependent inference can also occur during encoding and possibly also outside of awareness. Here, we sought to further explore the feasibility of hippocampal implicit inference, and specifically address the temporal evolution of implicit inference using intracranial EEG. Presurgical epilepsy patients with hippocampal depth electrodes viewed a sequence of word pairs, and judged the semantic fit between two words in each pair. Some of the word pairs entailed a common word (e.g., "winter-red," "red-cat") such that an indirect relation was established in following word pairs (e.g., "winter-cat"). The behavioral results suggested that drawing inference implicitly from past experience is feasible because indirect relations seemed to foster "fit" judgments while the absence of indirect relations fostered "do not fit" judgments, even though the participants were unaware of the indirect relations. A event-related potential (ERP) difference emerging 400 ms post stimulus was evident in the hippocampus during encoding, suggesting that indirect relations were already established automatically during encoding of the overlapping word pairs. Further ERP differences emerged later post-stimulus (1,500 ms), were modulated by the participants' responses and were evident during encoding and test. Furthermore, response-locked ERP effects were evident at test. These ERP effects could hence be a correlate of the interaction of implicit memory with decision-making. Together, the data map out a time-course in which the hippocampus automatically integrates memories from discrete but related episodes to implicitly influence future decision making. PMID- 26136109 TI - Biaxially stretchable supercapacitors based on the buckled hybrid fiber electrode array. AB - In order to meet the growing need for smart bionic devices and epidermal electronic systems, biaxial stretchability is essential for energy storage units. Based on porous single-walled carbon nanotube/poly(3,4-ethylenedioxythiophene) (SWCNT/PEDOT) hybrid fiber, we designed and fabricated a biaxially stretchable supercapacitor, which possesses a unique configuration of the parallel buckled hybrid fiber array. Owing to the reticulate SWCNT film and the improved fabrication technique, the hybrid fiber retained its porous architecture both outwardly and inwardly, manifesting a superior capacity of 215 F g(-1). H3PO4 polyvinyl alcohol gel with an optimized component ratio was introduced as both binder and stretchable electrolyte, which contributed to the regularity and stability of the buckled fiber array. The buckled structure and the quasi one dimensional character of the fibers endow the supercapacitor with 100% stretchability along all directions. In addition, the supercapacitor exhibited good transparency, as well as excellent electrochemical properties and stability after being stretched 5000 times. PMID- 26136108 TI - Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in Apc(Min/+) Mice. AB - American ginseng (Panax quinquefolius L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered Apc(Min/+) mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the Apc(Min/+) mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids, and carbohydrates were observed in Apc(Min/+) mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates, and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the Apc(Min/+) induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms. PMID- 26136110 TI - Neuroprotective, antiapoptotic and antioxidant effects of l-carnitine against caffeine-induced neurotoxicity in SH-SY5Y neuroblastoma cell line. AB - CONTEXT: Caffeine is the most widely consumed nervous stimulant that induces oxidative-mediated apoptosis and cell cycle arrest in neural cells. Due to low toxicity, high accumulation in neural cells, reduction of the free fatty acids and antioxidant property, l-carnitine (LC) is an interesting compound to be used in vivo against several neuropathies. OBJECTIVES: This study was conducted to evaluate the protective effect of LC against caffeine-induced cytotoxicity in SH SY5Y neuroblastoma cell line. MATERIALS AND METHODS: SH-SY5Y neuroblastoma cells were incubated with cytotoxic doses of caffeine (5 and 10 mM) in the presence or absence of LC (1 and 5 mM) for duration of 18-24 h. The antioxidant factors, DNA fragmentation and cytotoxic markers were assessed in treated cells. RESULTS: Our results showed that 5 mM LC for 18 h protected SH-SY5Y cells against cytotoxicity induced by both doses of caffeine. This protection was related to the inhibition of reactive oxygen species generation, the increase in the superoxide dismutase and catalase activities and glutathione content and the prevention of lipid peroxidation in cultured SH-SY5Y cells. Apoptosis markers such as DNA fragmentation and caspase-3 activity were also inhibited by 5 mM LC in caffeine treated cells. DISCUSSION AND CONCLUSION: Our results suggest that LC could protect SH-SY5Y cells from caffeine-induced injury through the inhibition of oxidative damage, mitochondria dysfunction and inhibition of cell apoptosis. Our results indicate that LC therapy may be a valuable approach for the suppression of oxidative stress-related apoptosis in various neural diseases. PMID- 26136111 TI - Selectively Activatable Latent Thiol and Selenolesters Simplify the Access to Cyclic or Branched Peptide Scaffolds. AB - The cyclic dichalcogenides based on the bis(2-chalcogenoethyl)amide structure are latent N,S (SEA, chalcogen = S) or N,Se (SeEA, chalcogen = Se) acyl shift systems. The large difference in the reducing potential between SEA and SeEA dichalcogenides allows their sequential and selective activation by reduction. Based on these concepts, one-pot three or four peptide segment assembly processes were designed, facilitating access to branched or cyclic peptide scaffolds. PMID- 26136112 TI - Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy. AB - Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA. PMID- 26136113 TI - Beneficial effects of levobupivacaine regional anaesthesia on postoperative opioid induced hyperalgesia in diabetic mice. AB - BACKGROUND: Diabetic neuropathy is one of the most common complications of diabetes and causes various problems in daily life. The aim of this study was to assess the effect of regional anaesthesia on post surgery opioid induced hyperalgesia in diabetic and non-diabetic mice. METHODS: Diabetic and non diabetic mice underwent plantar surgery. Levobupivacaine and sufentanil were used before surgery, for sciatic nerve block (regional anaesthesia) and analgesia, respectively. Diabetic and non-diabetic groups were each randomly assigned to three subgroups: control, no sufentanil and no levobupivacaine; sufentanil and no levobupivacaine; sufentanil and levobupivacaine. Three tests were used to assess pain behaviour: mechanical nociception; thermal nociception and guarding behaviours using a pain scale. RESULTS: Sufentanil, alone or in combination with levobupivacaine, produced antinociceptive effects shortly after administration. Subsequently, sufentanil induced hyperalgesia in diabetic and non-diabetic mice. Opioid-induced hyperalgesia was enhanced in diabetic mice. Levobupivacaine associated to sufentanil completely prevented hyperalgesia in both groups of mice. CONCLUSION: The results suggest that regional anaesthesia can decrease opioid-induced hyperalgesia in diabetic as well as in non-diabetic mice. These observations may be clinically relevant for the management of diabetic patients. PMID- 26136114 TI - Estimating bisphenol A exposure levels using a questionnaire targeting known sources of exposure. AB - OBJECTIVE: To develop a BPA Exposure Assessment Module (BEAM) for use in large observational studies and to evaluate the ability of the BEAM to estimate bisphenol A (BPA) exposure levels. DESIGN: The BEAM was designed by modifying an FFQ with questions targeting known sources of BPA exposure. Frequency of intake of known dietary sources of BPA was assessed using the BEAM and three 24 h food records as a reference diet measurement tool. Urinary BPA (uBPA) levels were measured as the criterion tool in a pooled urine sample (nine spot samples per participant). Spearman correlations, linear regression and weighted kappa analysis were used to evaluate the ability of the BEAM and food records to estimate BPA exposure levels. SETTING: Minneapolis/Saint Paul, MN, USA. SUBJECTS: Sixty-eight healthy adult (20-59 years) volunteers. RESULTS: Dietary BPA intake assessed by the BEAM was not associated with uBPA levels and was unable to predict participants' rank by uBPA levels. BEAM models with all a priori predictors explained 25 % of the variability in uBPA levels. Canned food intake assessed by food records was associated with uBPA levels, but was unable to rank participants by uBPA levels. Multivariable-adjusted food record models with a priori predictors explained 41 % of the variability in uBPA levels. CONCLUSIONS: Known dietary sources of BPA exposure explained less than half the variability in uBPA levels, regardless of diet assessment method. Findings suggest that a questionnaire approach may be insufficient for ranking BPA exposure level and additional important sources of BPA exposure likely exist. PMID- 26136115 TI - Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice. AB - BACKGROUND: Energy drinks are popular mixers with alcohol. While energy drinks contain many ingredients, caffeine is an important pharmacologically active component and is generally present in larger amounts than in other caffeinated beverages. In these studies, we investigated the hypothesis that caffeine would influence the effects of alcohol (ethanol [EtOH]) on conditioned taste aversion (CTA), ataxia, and locomotor activity (LA) after repeated exposure. METHODS: Four groups of mice were exposed by oral gavage twice daily to vehicle, EtOH (4 g/kg), caffeine (15 mg/kg), or the EtOH/caffeine combination. CTA to saccharin and ataxia in the parallel rod task was evaluated after 8 or 16 gavages, respectively, using EtOH (1 to 3 g/kg) or EtOH/caffeine (3 mg/kg + 2 g/kg) challenges. In addition, LA was evaluated initially and after repeated exposure to oral gavage of these drugs and doses. RESULTS: Repeated oral gavage of EtOH produced significant locomotor sensitization, with those mice increasing total distance traveled by 2-fold. The locomotor response to caffeine, while significantly greater than vehicle gavage, did not change with repeated exposure. On the other hand, repeated gavage of caffeine/EtOH combination produced a substantial increase in total distance traveled after repeated exposure (~4-fold increase). After repeated EtOH exposure, there was significant tolerance to EtOH in the CTA and parallel rod tests. However, neither a history of caffeine exposure nor including caffeine influenced EtOH-induced CTA. Interestingly, a history of caffeine exposure increased the ataxic response to the caffeine/EtOH combination and appeared to reduce the ataxic response to high doses of EtOH. CONCLUSIONS: The data support the general hypothesis that repeated exposure to caffeine influences the response to EtOH. Together with previously published work, these data indicate that caffeine influences some EtOH-related behaviors, notably locomotion and ataxia, but appears not to influence the expression of conditioned behaviors. PMID- 26136116 TI - Implementation of couples' voluntary HIV counseling and testing services in Durban, South Africa. AB - BACKGROUND: Couples' voluntary HIV counseling and testing (CVCT) is an evidence based intervention that significantly reduces HIV incidence in couples. Despite the high prevalence of HIV and HIV couple serodiscordance in South Africa, there are few CVCT services. METHODS: From February-June 2013, The Rwanda Zambia HIV Research Group provided support, training, and technical assistance for local counselors and promoters to pilot CVCT services in five hospital-based clinics in Durban, South Africa. Client-level data (age, gender, years cohabiting, pregnancy status, previous testing, antiretroviral treatment (ART) status, neighborhood, and test site) collected as a component of routine CVCT service operation is presented stratified by couple serostatus. RESULTS: Twenty counselors and 28 promoters completed training. Of 907 couples (1,814 individuals) that underwent CVCT, prevalence of HIV was 41.8% and prevalence of HIV serodiscordance was 29.5% (19.3% M-F+, 10.3% M + F-). Most participants were 25-34 years of age, and this group had the highest prevalence. Previous individual HIV testing was low (50% for men, 63% for women). Only 4% of couples reported previous CVCT. Most (75%) HIV+ partners were not on ART, and HIV+ individuals in discordant couples were more likely to be on ART than those in concordant positive couples. Pregnancy among HIV+ women was not associated with previous HIV testing or ART use. CONCLUSIONS: Implementation of standard CVCT services was found to be feasible in Durban. The burden of HIV and couple serodiscordance in Durban was extremely high. CVCT would greatly benefit couples in Durban as an HIV prevention strategy. PMID- 26136117 TI - Associations Between Marital Conflict and Adolescent Conflict Appraisals, Stress Physiology, and Mental Health. AB - The goal of the current study was to examine conflict appraisals and diurnal cortisol production as mediators of the robust association between marital conflict and adolescent adjustment problems. Parents reported their marital conflict and were observed engaging in a marital conflict discussion; they also reported adolescent internalizing and externalizing behaviors. Adolescents (n = 105, 52% female, 10-17 years of age) appraised their parents' marital conflict and reported their internalizing and externalizing behaviors. After the laboratory visit, adolescents provided four saliva samples on each of 2 consecutive days to assess diurnal cortisol production. More-negative marital conflict predicted more self-blame for parental conflict, which in turn predicted less robust decreases in cortisol across the day. Further, this flattened cortisol production pattern mediated the relationship between greater self-blame for parental conflict and adolescents' elevated internalizing behaviors. Feeling responsible for parental conflict appears to be particularly damaging in terms of physiological regulation and adjustment, and may therefore be a particularly useful intervention target. PMID- 26136118 TI - Identification of the first large deletion in the CLDN16 gene in a patient with FHHNC and late-onset of chronic kidney disease: case report. AB - BACKGROUND: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal disease characterized by tubular disorders at the thick ascending limb of Henle's loop. It is caused by mutations in the tight junction structural proteins claudin-16 or claudin-19, which are encoded by the CLDN16 and CLDN19 genes, respectively. Patients exhibit excessive wasting of calcium and magnesium, nephrocalcinosis, chronic kidney disease, and early progression to end-stage renal failure during infancy. CASE PRESENTATION: We here report the phenotype and molecular analysis of a female Brazilian patient with a novel large homozygous deletion in the CLDN16 gene. The proband, born from consanguineous parents, presented the first symptoms at age 20. Clinical examination revealed hypocalcemia, hypomagnesemia, nephrocalcinosis, mild myopia, high serum levels of uric acid and intact parathyroid hormone, and moderate chronic kidney disease (stage 3). She and her mother were subjected to CLDN16 and CLDN19 mutational analysis. In addition, the multiplex ligation-dependent probe amplification method was used to confirm a CLDN16 multi-exon deletion. Direct sequencing revealed a normal CLDN19 sequence and suggested a large deletion in the CLDN16 gene. Multiplex ligation-dependent probe amplification showed a homozygous CLDN16 multi-exon deletion (E2_E5del). The patient initiated conventional treatment for familial hypomagnesemia with hypercalciuria and nephrocalcinosis and progressed to end-stage kidney disease after five years. CONCLUSIONS: This study provides the first report of a large homozygous deletion in the CLDN16 gene causing familial hypomagnesemia with hypercalciuria and nephrocalcinosis with late onset of the first symptoms. This description expands the phenotypic and genotypic characterization of the disease. The late-onset chronic kidney disease in the presence of a homozygous deletion in the CLDN16 gene reinforces the great variability of genotype-phenotype manifestation in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. PMID- 26136119 TI - A Series of Multifunctional Metal-Organic Frameworks Showing Excellent Luminescent Sensing, Sensitization, and Adsorbent Abilities. AB - A series of highly luminescent-active metal-organic frameworks (MOFs) 1-3 with hierarchical pores have been rationally constructed and fully characterized. The predesigned semi-rigid hexacarboxylate ligand hexa[4-(carboxyphenyl)oxamethyl]-3 oxapentane acid (H6 L) has been adapted with various space-directed N donors (i.e., 2,2'-bipyridine, 4,4'-di(1H-imidazol-1-yl)-1,1'-biphenyl, and 1,3,5-tri(1H imidazol-1-yl)benzene) from a bidentate V-shape to a tridentate Y-shape. This family of multifunctional MOF materials represents a variety of potential applications in the following aspects: first, as luminescent sensors that show a fast and sensitive detection for pollutant CrO4 (2-) and Cr2 O7 (2-) ions in aqueous media; second, as adsorbents that can rapidly remove harmful organic dyes; third, as an antenna that can effectively sensitize visible-light-emitting Tb(3+) ions. These multifunctional MOF materials combine optical-sensing, adsorption, and sensitization properties, thus are very useful in many potential applications. Furthermore, these materials have proved to be reusable. PMID- 26136121 TI - Gene-Expression Profiles in Generalized Aggressive Periodontitis: A Gene Network Based Microarray Analysis. AB - BACKGROUND: In this study, molecular biomarkers that play a role in the development of generalized aggressive periodontitis (GAgP) are investigated using gingival tissue samples through omics-based whole-genome transcriptomics while using healthy individuals as background controls. METHODS: Gingival tissue biopsies from 23 patients with GAgP and 25 healthy individuals were analyzed using gene-expression microarrays with network and pathway analyses to identify gene-expression patterns. To substantiate the results of the microarray studies, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to assess the messenger RNA (mRNA) expression of MZB1 and DSC1. The microarrays and qRT-PCR resulted in similar gene-expression changes, confirming the reliability of the microarray results at the mRNA level. RESULTS: As a result of the gene-expression microarray studies, four significant gene networks were identified. The most upregulated genes were found as MZB1, TNFRSF17, PNOC, FCRL5, LAX1, BMS1P20, IGLL5, MMP7, SPAG4, and MEI1; the most downregulated genes were found as LOR, LAMB4, AADACL2, MAPT, ARG1, NPR3, AADAC, DSC1, LRRC4, and CHP2. CONCLUSIONS: Functions of the identified genes that were involved in gene networks were cellular development, cell growth and proliferation, cellular movement, cell-cell signaling and interaction, humoral immune response, protein synthesis, cell death and survival, cell population and organization, organismal injury and abnormalities, molecular transport, and small-molecule biochemistry. The data suggest new networks that have important functions as humoral immune response and organismal injury/abnormalities. Future analyses may facilitate proteomic profiling analyses to identify gene-expression patterns related to clinical outcome. PMID- 26136120 TI - [Early viscoelasticity-based coagulation therapy for severely injured bleeding patients: Report of the consensus group on the consensus conference 2014 for formulation of S2k guidelines]. AB - Although there is increasing interest in the use of a viscoelastic test procedure (ROTEM/TEG) for diagnostics and therapy guidance of severely injured and bleeding patients, currently no uniformly accepted guidelines exist for how this technology should be integrated into clinical treatment. In September 2014 an international multidisciplinary group of opinion leaders in the field of trauma induced coagulopathy and other disciplines involved in the treatment of severely injured patients were assembled for a 2-day consensus conference in Philadelphia (USA). This panel included trauma/accident surgeons, general/abdominal surgeons, vascular surgeons, emergency/intensive care surgeons, hematologists, transfusion specialists, anesthesiologists, laboratory physicians, pathobiologists/pathophysiologists and the lay public. A total of nine questions regarding the impact of viscoelastic testing in the early treatment of trauma patients were developed prior to the conference by a panel consensus. Early use was defined as baseline viscoelastic test result thresholds obtained within the first minutes of hospital arrival, when conventional laboratory results are not yet available. The available data for each question were then reviewed in person using standardized presentations by the expert panel. A consensus summary document was then developed and reviewed by the panel in an open forum. Finally, a 2-round Delphi poll was administered to the panel of experts regarding viscoelastic thresholds for triggering the initiation of specific treatments including fibrinogen (concentrates), platelet concentrates, blood plasma products and prothrombin complex concentrates (PCC). This report summarizes the findings and recommendations of this consensus conference, which correspond to a S2k guideline according to the system of the Association of the Scientific Medical Societies in Germany (AWMF) and taking formal consensus findings including Delphi methods into consideration. PMID- 26136122 TI - Intraperitoneal Infection of Wild-Type Mice with Synthetically Generated Mammalian Prion. AB - The prion hypothesis postulates that the infectious agent in transmissible spongiform encephalopathies (TSEs) is an unorthodox protein conformation based agent. Recent successes in generating mammalian prions in vitro with bacterially expressed recombinant prion protein provide strong support for the hypothesis. However, whether the pathogenic properties of synthetically generated prion (rec Prion) recapitulate those of naturally occurring prions remains unresolved. Using end-point titration assay, we showed that the in vitro prepared rec-Prions have infectious titers of around 104 LD50/MUg. In addition, intraperitoneal (i.p.) inoculation of wild-type mice with rec-Prion caused prion disease with an average survival time of 210-220 days post inoculation. Detailed pathological analyses revealed that the nature of rec-Prion induced lesions, including spongiform change, disease specific prion protein accumulation (PrP-d) and the PrP-d dissemination amongst lymphoid and peripheral nervous system tissues, the route and mechanisms of neuroinvasion were all typical of classical rodent prions. Our results revealed that, similar to naturally occurring prions, the rec-Prion has a titratable infectivity and is capable of causing prion disease via routes other than direct intra-cerebral challenge. More importantly, our results established that the rec-Prion caused disease is pathogenically and pathologically identical to naturally occurring contagious TSEs, supporting the concept that a conformationally altered protein agent is responsible for the infectivity in TSEs. PMID- 26136124 TI - A case of pseudotumoral malakoplakia following pathologic complete response in rectal cancer. PMID- 26136123 TI - Alpha 7-nicotinic acetylcholine receptor mediates the sensitivity of gastric cancer cells to 5-fluorouracil. AB - Gastric cancer is the second most common cause of cancer mortality worldwide. Most gastric cancer patients are asymptomatic until the advanced stages, for which current therapeutic treatments are suboptimal. 5-Fluorouracil (5-FU), an antimetabolite agent, is widely used in gastric cancer therapy. However, the presence of drug resistance in gastric cancer patients reduces the cytotoxic activity of 5-FU. In gastric cancer, no research has yet been conducted to analyze the effect of alpha 7-nicotinic acetylcholine receptor (A7-nAChR) on the therapeutic response to 5-FU. In this study, we generated A7-nAChR knockdown (A7 nAChR-KD) AGS cells by a small interfering RNA (siRNA) technique in gastric cancer cells. The anti-proliferative effects of 5-FU were determined by a 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, and cell cycle determination. We found that A7-nAChR-KD cells were more resistant to 5-FU treatment compared with the scrambled control cells according to the MTT assay. The apoptotic cell population was increased more in scrambled control cells treated with 5-FU than A7-nAChR-KD cells according to the cell cycle distribution and TUNEL assays. We analyzed expression levels of survival and apoptosis associated proteins (pAkt, Akt, Mcl-1, Bcl-2, Bad, and Bax) altered by 5-FU treatment. Survival and antiapoptosis signaling (pAkt, Akt, Mcl-1 and Bcl-2) was downregulated, and the proapoptotic proteins (Bad and Bax) were upregulated in 5 FU-treated control cells but expression levels of Bcl-2, Bad, and Bad were not altered in 5-FU-treated A7-nAChR-KD cells. This is consistent with A7-nAChR-KD cells exhibiting more resistance to 5-FU treatment. In our study, we carried out an in vitro study on AGS gastric cancer cell line to elucidate the anticancer efficacy and molecular mechanisms of A7-nAChR silencing on 5-FU-induced cell death. The results clearly showed that depletion of A7-nAChR suppressed the drug sensitivity of gastric cancer cells to 5-FU treatment. PMID- 26136125 TI - Two Adhesive Sites Can Enhance the Knotting Probability of DNA. AB - Self-entanglement, or knotting, is entropically favored in long polymers. Relatively short polymers such as proteins can knot as well, but in this case the entanglement is mainly driven by fine-tuned, sequence-specific interactions. The relation between the sequence of a long polymer and its topological state is here investigated by means of a coarse-grained model of DNA. We demonstrate that the introduction of two adhesive regions along the sequence of a self-avoiding chain substantially increases the probability of forming a knot. PMID- 26136126 TI - Blunt Cardiac Injury in the Severely Injured - A Retrospective Multicentre Study. AB - BACKGROUND: Blunt cardiac injury is a rare trauma entity. Here, we sought to evaluate the relevance and prognostic significance of blunt cardiac injury in severely injured patients. METHODS: In a retrospective multicentre study, using data collected from 47,580 patients enrolled to TraumaRegister DGU (1993-2009), characteristics of trauma, prehospital / hospital trauma management, and outcome analysis were correlated to the severity of blunt cardiac injury. The severity of cardiac injury was assessed according to the abbreviated injury score (AIS score 1-6), the revised injury severity score (RISC) allowed comparison of expected outcome with injury severity-dependent outcome. N = 1.090 had blunt cardiac trauma (AIS 1-6) (2.3% of patients). RESULTS: Predictors of blunt cardiac injury could be identified. Sternal fractures indicate a high risk of the presence of blunt cardiac injury (AIS 0 [control]: 3.0%; AIS 1: 19.3%; AIS 2-6: 19.1%). The overall mortality rate was 13.9%, minor cardiac injury (AIS 1) and severe cardiac injury (AIS 2-6) are associated with higher rates. Severe blunt cardiac injury (AIS 4 and AIS 5-6) is associated with a higher mortality (OR 2.79 and 4.89, respectively) as compared to the predicted average mortality (OR 2.49) of the study collective. CONCLUSION: Multiple injured patients with blunt cardiac trauma are at high risk to be underestimated. Careful evaluation of trauma patients is able to predict the presence of blunt cardiac injury. The severity of blunt cardiac injury needs to be stratified according to the AIS score, as the patients' outcome is dependent on the severity of cardiac injury. PMID- 26136127 TI - Dense mapping of the region of insulin gene VNTR in polycystic ovary syndrome in a population of women from Central Europe. AB - INTRODUCTION: Insulin gene VNTR was associated with polycystic ovary syndrome (PCOS) in some studies but not in others. This couldb be due to the heterogeneity of the definition of PCOS and/or the use of inappropriate gene mapping strategies. MATERIAL AND METHODS: In this investigation, the association of VNTR with PCOS was explored in a population of women from Central Europe (377 cases and 105 controls) in whom PCOS was diagnosed according to Rotterdam criteria. Seven SNPs: rs3842756 (G/A), rs3842755 (G/T), rs3842754 (C/T), rs3842753 (A/C), rs3842752 (C/T), rs3842748 (G/C), and rs689 (T/A) were genotyped in a portion of the population (160 cases and 95 controls) by sequencing or by SSO-PCR. Analysis of linkage disequilibrium (LD) pattern allowed selecting three tagSNPs (rs3842754, rs3842748, and rs689), which were genotyped in the rest of the population by KASPar. RESULTS: Six haplotypes were reconstructed, among which three (h1, h2 and h6) were more frequent. Statistical analysis allowed observation of the association of the SNP rs3842748, through its GC genotype, with obesity in PCOS (P = 0.049; OR CI95% 1,59 [1.00-2.51]) and in classical PCOS (YPCOS) (P = 0.010), as well as the correlation of the SNP rs689 and the pair of haplotypes h1/h1 with higher levels of testosteronaemia in the PCOS group, although this was at the limit of significance (P = 0.054) CONCLUSION: These results are in accordance with some studies in literature and highlight the role of insulin gene VNTR in complex metabolic disorders. PMID- 26136128 TI - Assessment of platelet function in endogenous hypercortisolism. AB - INTRODUCTION: It is commonly known that glucocorticoids exert a significant effect on haemostasis. Studies that have analysed the plasmatic coagulation system and fibrinolysis parameters in hypercortisolaemic patients are abundant. Platelet function, which plays a vital role in primary haemostasis, is much less clear in this context. We aimed at assessing platelet function in endogenous hypercortisolaemic patients. MATERIAL AND METHODS: Twenty-five hypercortisolaemic patients were included in the study. Twelve of them were diagnosed with overt Cushing's syndrome (OCS) and 13 had subclinical Cushing's syndrome (SCS). Thirty healthy volunteers comprised the control group. In all subjects platelet function parameters were examined: ADP- and collagen-induced platelet aggregation (ADP-IPA and Col-IPA, respectively), IMPACT R (expressed as percentage of surface covered (SC) by platelets and average size (AS) of the adhering particles in MUm2), as well as closure time (CT) after platelet activation with agonists: ADP and Col or Col and epinephrine (EPI). The statistical significance level was set at 0.05. RESULTS: There was no significant difference in mean values of ADP-IPA, Col-IPA, Col/Epi CT, Col/ADP CT, SC, and AS between hypercortisolaemic subjects and controls. No statistically significant differences in means of examined parameters were found between overt and subclinical Cushing's syndrome patients. Furthermore, no statistically significant relationships were found between these parameters and hormonal indicators of hypercortisolism: 24-hour urinary cortisol excretion, morning and evening serum cortisol level, and overnight-test cortisol concentration. CONCLUSIONS: In hypercortisolaemic patients no primary haemostasis disorders are present, as reflected by platelet adhesion and ADP- and collagen induced aggregation measurements. PMID- 26136129 TI - Is adiponectin a risk factor for transient ischaemic attacks? AB - Adiponectin is an adipocytokine, and it plays a role in atherosclerosis. The role of adiponectin in the development of ischaemic stroke is controversial. Up to now, adiponectin was not evaluated in transient ischaemic stroke. In this study, we investigated the relationship between adiponectin and transient ischaemic attack. Forty patients with transient ischaemic attack were included into the study. In all patients, traditional risk factors of ischaemic stroke and intima media thickness of carotid arteries were determined. Also, the relationship between these parameters and adiponectin levels were examined. No difference was found in terms of adiponectin levels between patients and healthy subjects. In addition, there was no association between adiponectin levels and traditional risk factors. Our results suggest that adiponectin may not be a predictive risk factor of transient ischaemic attack. PMID- 26136130 TI - Serum parathyroid hormone concentrations measured by chemiluminescence and electrochemiluminescence methods - are the results comparable in haemodialysis patients with chronic kidney disease? AB - INTRODUCTION: Secondary hyperparathyroidism (sHPT) is one of the most common abnormalities found in patients with chronic kidney disease (CKD). Measurement of serum PTH concentrations is crucial in diagnosis and treatment of sHPT. Different methods of serum PTH measurement may provide diverse results. This may have a significant impact on the therapeutic approach if under- or over-diagnosis of sHPT occurs. The aim of this study was to compare the results of serum PTH concentrations measured with two commonly used methods - chemiluminescence (CHL) and electrochemiluminescence (ECL). MATERIAL AND METHODS: Seventy-seven haemodialysis patients with CKD were enrolled into the study. Blood samples were collected before haemodialysis, in the middle of the week. In all patients, serum PTH concentrations were measured using two methods: CHL and ECL. RESULTS: Serum PTH concentration measured with CHL was significantly higher than that assessed with ECL: 455 pg/mL (352-559) pg/mL vs. 383 pg/mL (243-523) pg/mL; p < 0.0001. Six patients from the studied cohort were treated with cinacalcet. In these patients, the serum PTH concentration was also significantly higher when measured with CHL than with ECL: 755 pg/mL (294-1216) pg/mL and 607 pg/mL (199-1015 pg/mL); p = 0.027, respectively). In three cases serum PTH concentration assessed with CHL method exceeded 300 pg/mL, whereas when measured with ECL it was below 300 pg/mL. Lower serum PTH concentrations could give the rationale to lower cinacalcet dose or to stop such treatment. CONCLUSIONS: 1. Serum PTH concentrations in haemodialysis patients with CKD measured by CHL and ECL methods differ significantly. 2. The choice of method for measurement of serum PTH concentration in these patients may have important clinical implications. PMID- 26136131 TI - Comparison of the effects of hypolipidemic treatment on monocyte proinflammatory cytokine release in men and women with type 2 diabetes and atherogenic dyslipidemia. AB - INTRODUCTION: Statins and fibrates reduce monocyte release of proinflammatory cytokines, but it remains unknown whether this effect is sex dependent. MATERIAL AND METHODS: We retrospectively analysed age-, weight-, and lipid-matched populations of type 2 diabetic patients of both sexes, who, because of atherogenic dyslipidaemia, were treated with simvastatin (40 mg daily), fenofibrate (200 mg daily), or simvastatin plus fenofibrate. Monocyte release of tumour necrosis factor alpha (TNF-alpha), inteleukin-1beta, interleukin-6, and monocyte chemoattractant protein-1 (MCP-1), as well as circulating levels of high sensitivity C-reactive protein (hsCRP) and free fatty acids (FFA) were assessed separately for men and women before and after 12 weeks of treatment. RESULTS: Baseline monocyte release of TNF-alpha, interleukin-1beta, interleukin-6, and MCP 1, as well as plasma hsCRP and FFA levels were comparable in both sexes. Simvastatin, fenofibrate, and simvastatin/fenofibrate combination therapy reduced monocyte release of TNF-alpha, inteleukin-1beta, interleukin-6, and MCP-1, with no difference between the treatment groups. The impact of simvastatin and fenofibrate administered alone on monocyte cytokine release and systemic inflammation did not differ between the men and women. The effect of simvastatin/fenofibrate combination therapy on monocyte release of interleukin-6 and MCP-1 was more pronounced in the male population. The impact of simvastatin administered together with fenofibrate on TNF-alpha, interleukin-1beta, and hsCRP was also stronger in the men than in the women, but the difference did not reach the level of significance. CONCLUSIONS: The obtained results suggest that sex differences determine the strength of the monocyte-suppressing effect of simvastatin/ /fenofibrate combination therapy in type 2 diabetic patients with atherogenic dyslipidaemia. PMID- 26136132 TI - How often do we see incidental 68Ga-DOTATATE thyroid uptake in PET/CT in patients with neuroendocrine tumours? AB - INTRODUCTION: Thyroid diseases, which may occur as focal or diffuse changes in thyroid parenchyma, are most often observed in women. AIM: Our aim was to assess the prevalence of incidental thyroid uptake of 68Ga-DOTATATE PET/CT in patients referred to the Nuclear Medicine Department for evaluation of neuroendocrine neoplasia (NEN). MATERIAL AND METHODS: We retrospectively evaluated 1150 68Ga DOTATATE PET/CT images. Clinical history, serum TSH and thyroid antibody (TAb) concentrations, ultrasonography, and cytological assessment of the material from fine-needle aspiration biopsy (FNA) of the thyroid lesion were investigated. RESULTS: We found incidental abnormalities in 46/1150 (4.1%) patients (12 men, 34 women). 34/46 patients (8 men, 26 women) showed diffuse 68Ga-DOTATATE thyroid uptake, with mean SUVmax 4.6 +/- 1.6. Based on laboratory tests and ultrasound, we found: 38% of patients with an active autoimmune thyroiditis, 27% with benign goitre, and 6% with multinodular goitre with autoimmune thyroiditis. The remaining 29% of patients did not show any pathology. In 12/47 patients (4 men, 8 women) focal uptake in the thyroid with SUVmax 7.3 +/- 3.3 was found. During one year follow-up, category II and category III lesions (according to Bethesda classification) were revealed in 9/12 (75%) patients and in one patient, respectively. Histopathological examination after surgery revealed papillary thyroid carcinoma in one patient and benign multinodular goitre in another patient. CONCLUSIONS: Patients with focal 68Ga-DOTATATE uptake should undergo further examination (FNA) due to potential risk of malignancy. Diffuse 68Ga DOTATATE uptake was predominantly associated with active autoimmune thyroiditis or benign goitre. The focal lesions and diffuse pathology diseases were frequently seen in women. PMID- 26136133 TI - Effect of intravenous versus subcutaneous insulin delivery on the intensity of neuropathic pain in diabetic subjects. AB - INTRODUCTION: The effectiveness of treatment of painful diabetic polyneuropathy remains unsatisfactory. The aim of this study was to compare effects of intravenous vs. subcutaneous insulin delivery in patients with diabetic symmetric sensorimotor polyneuropathy on pain relief, the quality of life, sleep disturbance, and the nerve conduction. MATERIAL AND METHODS: Thirty-four patients with diabetic polyneuropathy (mean age 62 +/- 10 years, duration 17 +/- 10 years), who reached a pain score over 40 mm on the VAS scale, HbA(1c) 7.5-10%, were randomly assigned to continuous intravenous insulin infusion (examined group) and multiple injections (control subjects). Before and after five days of the insulin treatment the effects on pain relief (SFMPQ-VAS), the quality of life improvement (EuroQol EQ-5D), and sleep disturbances (AIS) were assessed. RESULTS: Both groups experienced significant pain reduction, improvement of the quality of life, and reduction of sleep disturbances, i.e. a VAS in the study group of 69 +/ 14 mm before treatment vs. 40 +/- 19 mm after treatment (p < 0.001), and in control subjects 66 +/- 16 mm vs. 47 +/- 17 mm (p < 0.001). No difference in level of pain intensity reduction between the groups studied was found. CONCLUSIONS: Intensification of insulin treatment applied for five days results in improvement of the physical condition of patients with painful diabetic polyneuropathy, through pain relief, and improvement of the quality of life and sleep quality. The efficacy of insulin intravenous infusion and multiple injections is comparable. PMID- 26136134 TI - The effects of iodised salt licks and teat dipping on the iodine content of cow's milk and blood plasma. AB - INTRODUCTION: Milk has been identified as the ideal carrier of iodine in the human diet. The iodine concentration in cow's milk depends on the iodine intake in the animal's daily rations. MATERIALS AND METHODS: The first experiment, which lasted for 90 days, investigated the effectiveness of salt licks containing 0 (control group), 150, and 300 mg I/kg (experimental groups) and the effect on the iodine content of cow's milk and blood plasma. The second experiment determined the effect of udder disinfection and iodine teat dipping with iodine disinfectant (experimental group) compared to chlorine dip (control group) on the iodine content of milk and blood plasma. Milk iodine and blood plasma concentrations were meas- ured using the Sandell-Kolthoff method modified by the Bobek and Kolczak procedure. RESULT: Salt licks containing 150 and 300 mg I/kg increased iodine intake by 7.5 and 15.0 mg I/day, respectively. Average iodine intake in the control group was 6.23 mg I/day, and 13.68 and 21.10 mg I/day in the experimental groups, respectively. There were no significant differences in the average cows' milk yield, which averaged 21.0 +/- 1.1 kg/day. Average milk iodine content was 53.8 MUg/1000 mL (control group), 65.0 and 84.7 MUg/1000 mL (experimental groups). Average plasma iodine content tended to increase in the experimental groups, but the differences between the groups were not significant. In the second experiment iodine udder disinfection and teat dipping increased average milk iodine content from 44.0 +/- 1.6 to 59.3 +/- 2.3 MUg/1000 mL. Average plasma iodine content increased only slightly, with a non- significant difference between the control and experimental groups. CONCLUSION: The iodine content of salt licks at 150 and 300 mg I/kg makes it possible to obtain from 65 to 85 MUg I/1000 mL of cow's milk. Pre-milking udder hygiene and post-milking iodine teat dipping additionally increase the iodine content of milk by around 15 MUg I/1000 mL milk, i.e. an increase of 35% in relation to cows from the control group. PMID- 26136135 TI - Functional hypothalamic amenorrhoea - diagnostic challenges, monitoring, and treatment. AB - Functional hypothalamic amenorrhoea (FHA) is associated with functional inhibition of the hypothalamic-pituitary-ovarian axis. Causes of FHA can be classified into the three groups: 1) stress-related factors, 2) consequences of weight loss and/or underweight, and 3) consequences of physical exercise or practicing sports. Diagnosis of FHA should be based on a history of menstrual disorders. During physical examination, patients with FHA present with secondary and tertiary sex characteristics specific for the pubertal stage preceding development of the condition and with the signs of hypoestrogenism. Laboratory results determine further management of patients with amenorrhea, and thus their correct interpretation is vital for making appropriate therapeutic decisions. Treatment of chronic anovulation, menstrual disorders, and secondary amenorrhea resulting from hypothalamic disorders should be aimed at the elimination of the primary cause, i.e. a decrease in psycho-emotional strain, avoidance of chronic stressors, reduction of physical exercise level, or optimisation of BMI in patients who lose weight. If menses do not resume after a period of six months or primary causative treatment is not possible, neutralisation of hypoestrogenism consequences, especially unfavourable effects on bone metabolism, become the main issue. Previous studies have shown that oestroprogestagen therapy is useful in both the treatment of menstrual disorders and normalisation of bone mineral density. Hormonal preparations should be introduced into therapeutic protocol on an individualised basis. PMID- 26136136 TI - Primary hyperparathyroidism in pregnancy - a diagnostic and therapeutic challenge. AB - Hypercalcaemia during pregnancy is uncommon, and mostly associated with primary hyperparathyroidism (pHPT). If unrecognised, it poses a significant risk for the mother and the foetus. Maternal symptoms include: hyperemesis, muscle weakness, pancreatitis, nephrolithiasis, bone disease, mental status changes, and hypercalcaemic crisis. Untreated disease complicates foetal development and foetal death is a significant risk. Our case illustrates the difficulty in detecting pHPT during pregnancy, serious complications connected with severe hypercalcaemia, and difficulties in preparing the patient for surgical treatment. Our review of the medical literature did not identify any previous case of a pregnant woman with hypercalcaemic crisis (total calcium 17 mg/dL, parathyroid hormone 2302 pg/mL), acute pancreatitis caused by pHPT, and with hyperthyroidism, who had undergone a successful surgical treatment. PMID- 26136137 TI - Polish Society of Endocrinology Position statement on endocrine disrupting chemicals (EDCs). AB - With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland. PMID- 26136138 TI - High Mannose-Binding Lectin Serum Levels Are Associated with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes. AB - OBJECTIVE: To investigate mannose-binding lectin (MBL) serum levels in type 2 diabetic patients with and without diabetic retinopathy (DR). METHODS: Serum MBL levels were determined in type 2 diabetic patients (N=324) as well as in 300 healthy control Subjects. Multivariate analyses were performed using logistic regression models. Receiver operating characteristic curves (ROC) was used to test the overall predict accuracy of MBL and other markers. RESULTS: Diabetic patients with DR and vision-threatening diabetic retinopathy (VTDR) had significantly higher MBL levels on admission (P<0.0001 and P<0.0001). MBL improved the area under the receiver operating characteristic curve of the diabetes duration for DRfrom 0.82(95% confidence interval [CI], 0.77-0.86) to 0.88(95% CI, 0.82-0.96; P<0.01) and for VDTR from 0.85(95% CI, 0.77-0.92) to 0.90(95% CI, 0.83-0.96; P<0.01). Multivariate logistic regression analysis adjusted for common risk factors showed that serum MBL levels(per log-unit increase) was an independent predictor of DR (OR=3.45; 95%CI: 1.42-7.05) and VTDR (OR=4.42; 95%CI: 1.51-8.18). CONCLUSION: MBL is a novel, independent diagnostic marker of DR in type 2 diabetic patients, suggesting that MBL may be involved in the pathogenesis of DR in diabetic patients. PMID- 26136139 TI - Processing and Characterization of SrTiO3-TiO2 Nanoparticle-Nanotube Heterostructures on Titanium for Biomedical Applications. AB - Surface properties such as physicochemical characteristics and topographical parameters of biomaterials, essentially determining the interaction between the biological cells and the biomaterial, are important considerations in the design of implant materials. In this study, a layer of SrTiO3-TiO2 nanoparticle-nanotube heterostructures on titanium has been fabricated via anodization combined with a hydrothermal process. Titanium was anodized to create a layer of titania (TiO2) nanotubes (TNTs), which was then decorated with a layer of SrTiO3 nanoparticles via hydrothermal processing. SrTiO3-TiO2 heterostructures with high and low volume fraction of SrTiO3 nanoparticle (denoted by 6.3-Sr/TNTs and 1.4-Sr/TNTs) were achieved by using a hydrothermal processing time of 12 and 3 h, respectively. The in vitro biocompatibility of the SrTiO3-TiO2 heterostructures was assessed by using osteoblast cells (SaOS2). Our results indicated that the SrTiO3-TiO2 heterostructures with different volume fractions of SrTiO3 nanoparticles exhibited different Sr ion release in cell culture media and different surface energies. An appropriate volume fraction of SrTiO3 in the heterostructures stimulated the secretion of cell filopodia, leading to enhanced biocompatibility in terms of cell attachment, anchoring, and proliferation on the heterostructure surface. PMID- 26136140 TI - Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells. AB - Honokiol (HNK), a potential antitumor compound, has been widely studied in recent years. It induces apoptosis and affects autophagy in cancer cells, yet the mechanism of its antitumor efficacy remains obscure. Chloroquine (CQ), an autophagy inhibitor, is often applied to sensitize antitumor drugs in clinical trials. Here, we investigated the antitumor effect of HNK or CQ alone or in combination in non-small cell lung cancer (NSCLC) cells. Using an experimental approach, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or sulforhodamine B (SRB) was used to determine the cytotoxicity of the agents. The expression levels of proteins were detected by western blotting. Apoptosis was examined via Annexin V-FITC and PI staining. H460 cell xenografts in nude mice were used to study the effects of HNK and/or CQ in vivo. Transfection with siRNA was applied to knock down cathepsin D. The results demonstrated the enhanced effects of HNK combined with CQ on the inhibition of proliferation, induction of apoptosis in vitro and the reduction in growth in vivo. It was confirmed that HNK and/or CQ triggered apoptosis via a caspase-dependent manner. Furthermore, HNK significantly increased the expression of p62 and LC3-II in the A549 and H460 cells and inhibited autophagy and induced apoptosis in a cathepsin D-involved manner. In conclusion, an enhanced antitumor effect was demonstrated following treatment with HNK combined with CQ by inhibiting autophagy and inducing apoptosis via a caspase-dependent and cathepsin D-involved manner. This combination may be a novel and useful antitumor approach for chemotherapy in NSCLC. PMID- 26136142 TI - Switching and Conformational Fixation of Amides Through Proximate Positive Charges. AB - Tertiary amides, which usually occur as cis/trans mixtures, can be effectively shifted to the cis conformation by placing a positive charge in close proximity to the amide carbonyl. This effect was used to prepare cis-configured prolyl amides and to facilitate a strongly rotamer-dependent radical cyclization. PMID- 26136141 TI - Evidence for holistic episodic recollection via hippocampal pattern completion. AB - Recollection is thought to be the hallmark of episodic memory. Here we provide evidence that the hippocampus binds together the diverse elements forming an event, allowing holistic recollection via pattern completion of all elements. Participants learn complex 'events' from multiple overlapping pairs of elements, and are tested on all pairwise associations. At encoding, element 'types' (locations, people and objects/animals) produce activation in distinct neocortical regions, while hippocampal activity predicts memory performance for all within-event pairs. When retrieving a pairwise association, neocortical activity corresponding to all event elements is reinstated, including those incidental to the task. Participant's degree of incidental reinstatement correlates with their hippocampal activity. Our results suggest that event elements, represented in distinct neocortical regions, are bound into coherent 'event engrams' in the hippocampus that enable episodic recollection--the re experiencing or holistic retrieval of all aspects of an event--via a process of hippocampal pattern completion and neocortical reinstatement. PMID- 26136143 TI - Anticoagulant activity of native and partially degraded glycoglucuronomannan after chemical sulfation. AB - Heparin has great clinical importance as anticoagulant and antithrombotic agent. However, because of its risks of causing bleeding and contamination by animal pathogens, several studies aim to obtain alternatives to heparin. In the search for anticoagulant and antithrombotic agents from a non-animal source, a glycoglucuronomannan from the gum exudate of the plant Vochysia thyrsoidea was partially hydrolyzed, and both native and partially degraded polysaccharides were chemically sulfated, yielding VThS and Ph-VThS respectively. Methylation analysis indicated that sulfation occurred preferentially at the O-5 position of arabinose units in the VThS and at the O-6 position of mannose units in Ph-VThS. In vitro aPTT assay showed that VThS and Ph-VThS have anticoagulant activity, which could be controlled by protamine, and ex vivo aPTT assay demonstrated that Ph-VThS is absorbed by subcutaneous route. Like heparin, they were able to inhibit alpha thrombin and factor Xa by a serpin-dependent mechanism. In vivo, VThS and Ph-VThS reduced thrombus formation by approximately 50% at a dose of 40 IU/kg, similarly to heparin. The results demonstrated that the chemically sulfated polysaccharides are promising anticoagulant and antithrombotic agents. PMID- 26136144 TI - A novel protein with anti-metastasis activity on 4T1 carcinoma from medicinal fungus Cordyceps militaris. AB - Cordyceps militaris is a famous fungus used in traditional Chinese medicine for nearly one thousand years. And its fruiting body is known to possess anticancer and immunomodulatory activities. This study describes the isolation, characterization, and test of antitumor activity of a C. militaris protein, called here as "C. militaris immunoregulatory protein" (CMIP). CMIP was purified through a three-step chromatographic procedure. The MS analyses showed that CMIP corresponded to an uncharacterized protein (CCM_01955) in the C. militaris transcriptional database. Circular dichroism of CMIP revealed the composition of 35.5% beta-sheet, 18.5% alpha-helix, 17.0% turn and 29.0% random coil. No significant cytotoxicity of CMIP was observed on HeLa, HepG2 and 4T1 tumor cells. However, CMIP demonstrated anti-metastasis activity on a mouse model of 4T1 breast cancer lung metastasis. It reduced the number of tumor nodules in the lung of tumor-bearing mice and prolonged their survival time. Furthermore, proliferation of the 4T1 cells was inhibited by macrophage-CMIP conditioned media. And the mRNA levels of cytokines TNF-alpha, IL-1beta and IL-6 were increased significantly in peritoneal macrophages treated by CMIP. These results reveal the antitumor potential of CMIP, thus reinforcing the importance of biochemical prospecting of C. militaris. PMID- 26136146 TI - Reproducibility of Variant Calls in Replicate Next Generation Sequencing Experiments. AB - Nucleotide alterations detected by next generation sequencing are not always true biological changes but could represent sequencing errors. Even highly accurate methods can yield substantial error rates when applied to millions of nucleotides. In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.2 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls. The concordance rates over the entire sequenced region were >99.99%, while the concordance rates for SNVs were 54.3 75.5%. There was substantial variation in basic sequencing metrics from experiment to experiment. The type of nucleotide substitution and genomic location of the variant had little impact on concordance but concordance increased with coverage level, variant allele count (VAC), variant allele frequency (VAF), variant allele quality and p-value of SNV-call. The most important determinants of concordance were VAC and VAF. Even using the highest stringency of QC metrics the reproducibility of SNV calls was around 80% suggesting that erroneous variant calling can be as high as 20-40% in a single experiment. The sequence data have been deposited into the European Genome phenome Archive (EGA) with accession number EGAS00001000826. PMID- 26136145 TI - Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders. AB - Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual's brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc) following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs) play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD. PMID- 26136147 TI - Factors Associated with Acute and Chronic Hydrocephalus in Nonaneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Hydrocephalus requiring external ventricular drain (EVD) or shunt placement commonly complicates aneurysmal subarachnoid hemorrhage (SAH), but its frequency is not as well known for nonaneurysmal SAH (NA-SAH). Those with diffuse bleeding may have greater risk of hydrocephalus compared to those with a perimesencephalic pattern. We evaluated the frequency of hydrocephalus in NA-SAH and whether imaging factors could predict the need for EVD and shunting. METHODS: We collected admission clinical and imaging variables for 105 NA-SAH patients, including bicaudate index (BI), Hijdra sum score (HSS), intraventricular hemorrhage (IVH) score, modified Fisher scale (mFS), and bleeding pattern. Hydrocephalus was categorized as acute (need for EVD) or chronic (shunt). We applied logistic regression to determine whether hydrocephalus risk was independently related to bleeding pattern or mediated through blood volume or ventriculomegaly. RESULTS: Acute hydrocephalus was seen in 26 (25%) patients but was more common with diffuse (15/28, 54%) versus perimesencephalic (10/59, 17%, p < 0.001) bleeding. Patients developing acute hydrocephalus had worse clinical grade and higher BI, HSS, and IVH scores. Adjusting the relationship between hydrocephalus and diffuse bleeding for HSS (but not BI) nullified this association. Nine (35%) patients requiring EVD eventually required shunting for chronic hydrocephalus, which was associated with greater blood burden but not poor clinical grade. CONCLUSION: Acute hydrocephalus occurs in one-quarter of NA SAH patients. The greater risk in diffuse bleeding appears to be mediated by greater cisternal blood volume but not by greater ventriculomegaly. Imaging characteristics may aid in anticipatory management of hydrocephalus in NA-SAH. PMID- 26136148 TI - Intraspinal Pressure Monitoring in a Patient with Spinal Cord Injury Reveals Different Intradural Compartments: Injured Spinal Cord Pressure Evaluation (ISCoPE) Study. AB - BACKGROUND: We recently described a technique for monitoring intraspinal pressure (ISP) after traumatic spinal cord injury (TSCI). This is analogous to intracranial pressure monitoring after brain injury. We showed that, after severe TSCI, ISP at the injury site is elevated as the swollen cord is compressed against the dura. METHODS: In a patient with complete thoracic TSCI, we sequentially monitored subdural ISP above the injury, at the injury site, and below the injury intraoperatively. Postoperatively, we simultaneously monitored subdural ISP and intraparenchymal ISP at the injury site and compared the two ISP signals as well as their Fast Fourier Transform spectra. RESULTS: Subdural ISP recorded from the injury site was higher than subdural ISP recorded from above or below the injury site by more than 10 mmHg. The subdural and intraparenchymal ISP signals recorded from the injury site had comparable amplitudes and Fast Fourier Transform spectra. Intraparenchymal pulse pressure was twofold larger than subdural pulse pressure. CONCLUSION: After severe TSCI, three intradural compartments form (space above injury, injury site, space below injury) with different ISPs. At the level of maximum spinal cord swelling (injury site), subdural ISP is comparable to intraparenchymal ISP. PMID- 26136149 TI - The Application of "Renal Pedicle Rotation" Method in Retroperitoneal Laparoscopic Partial Nephrectomy for Renal Ventral Tumors. AB - OBJECTIVES: To present preliminary experience of "renal pedicle rotation" method in retroperitoneal laparoscopic partial nephrectomy (RLPN) for renal ventral tumors. METHODS: A retrospective analysis of renal surgery database about patients undergoing RLPN was conducted. We identified 14 consecutive cases of all the surgeries from December 2013 to October 2014 with renal ventral tumors. The 14 surgeries were all in the application of renal pedicle rotation method, an intraoperative skill in which surgeons rotates the kidney on renal pedicle axis after separating renal artery and vein for a better tumor exposure. RESULTS: A total of 14 patients underwent RLPN. All surgeries were successful without conversion to radical nephrectomy or open partial nephrectomy. The mean operative time was 171.1+/-47.2 min (range 83-246), the mean warm ischemia time was 15.9+/ 9.8 min (range 7-35) and the mean estimated blood loss was 89.3+/-102.2 mL (range 10-300). Mean postoperative hospital stay was 6.2+/-1.9 days (range 4-10) and mean retroperitoneal drainage was 4.2+/-1.4 days (range 2-8). No intraoperative complications occurred. Postoperative complications developed in four patients. All patients had negative margins and pathological examination revealed 10 (71.4%) clear cell carcinomas, two (14.2%) epithelial renal angiomyolipoma, one (7.1%) papillary carcinoma and one (7.1%) nephrotuberculosis. The review of the early oncologic outcomes revealed no local recurrence and distant metastasis. CONCLUSION: The renal pedicle rotation method might be a feasible and safe procedure to get a better tumor exposure for incision and suture in renal ventral tumors RLPN surgeries with acceptable postoperative outcomes. PMID- 26136150 TI - Re-visiting the nature and relationships between neurological signs and neurocognitive functions in first-episode schizophrenia: An invariance model across time. AB - The present study examined different types of neurological signs in patients with first-episode schizophrenia and their relationships with neurocognitive functions. Both cross-sectional and longitudinal designs were adopted with the use of the abridged Cambridge Neurological Inventory which comprises items capturing motor coordination, sensory integration and disinhibition. A total of 157 patients with first-episode schizophrenia were assessed at baseline and 101 of them were re-assessed at six-month interval. A structural equation model (SEM) with invariance model across time was used for data analysis. The model fitted well with the data at baseline assessment, X^2(21) = 21.78, p = 0.413, NFI = 0.95, NNFI = 1.00, CFI = 1.00, IFI = 1.00, RMSEA = 0.015. Subsequent SEM analysis with invariance model at six-month interval also demonstrated the same stable pattern across time and showed strong measurement invariance and structure invariance across time. Our findings suggest that neurological signs capture more or less the same construct captured by conventional neurocognitive tests in patients with schizophrenia. The measurement and structure of these relationships appear to be stable over time. PMID- 26136151 TI - MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68. AB - Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism of NB remains to be elucidated. In the present study, reverse transcription quantitative polymerase chain reaction data demonstrated that the expression of Sam68 was significantly upregulated in NB tissues compared with their matched adjacent normal tissues. Furthermore, it was revealed that reduced expression of miR-203 and increased expression of Sam68 co existed in NB tissues. Knockdown of Sam68 reduced the proliferation, migration and invasion of human SK-N-SH and SH-SY5Y NB cells. Similarly, overexpression of miR-203 also inhibited the proliferation, migration and invasion of these two cell lines. It was further demonstrated that the protein expression level of Sam68 was negatively mediated by miR-203 in the SK-N-SH and SH-SY5Y NB cells. Additionally, data from a dual luciferase reporter assay confirmed that miR-203 directly targeted Sam68 by binding to its 3'-untranslated region. In conclusion, the present study suggested for the first time, to the best of our knowledge, that the aberrant downregulation of miR-203 may contribute to the aberrant upregulation of Sam68 in NB and that miR-203 has an inhibitory role in malignant progression of NB by targeting Sam68. The present study provided evidence to support miR-203/Sam68 as a novel diagnostic or therapeutic targets for NB. PMID- 26136152 TI - Raman shift and electrical properties of MoS2 bilayer on boron nitride substrate. AB - We have fabricated a bilayer molybdenum disulphide (MoS2) transistor on boron nitride (BN) substrate and performed Raman spectroscopy and electrical measurements with this device. The characteristic Raman peaks show an upshift about 2.5 cm(-1) with the layer lying on BN, and a narrower line width in comparison with those on a SiO2 substrate. The device has a maximum drain current larger than 1 MUA and a high current on/off ratio of greater than 10(8). In the temperature range of 100 K-293 K, the two terminal gate effect mobility and the carrier density do not change significantly with temperature. Results of the Raman and electrical measurements reveal that BN is a suitable substrate for atomic layer electrical devices. PMID- 26136153 TI - Reliability of the Dutch-language version of the Communication Function Classification System and its association with language comprehension and method of communication. AB - AIM: The aims of this study were to determine the intra- and interrater reliability of the Dutch-language version of the Communication Function Classification System (CFCS-NL) and to investigate the association between the CFCS level and (1) spoken language comprehension and (2) preferred method of communication in children with cerebral palsy (CP). METHOD: Participants were 93 children with CP (50 males, 43 females; mean age 7y, SD 2y 6mo, range 2y 9mo-12y 10mo; unilateral spastic [n=22], bilateral spastic [n=51], dyskinetic [n=15], ataxic [n=3], not specified [n=2]; Gross Motor Function Classification System level I [n=16], II [n=14], III, [n=7], IV [n=24], V [n=31], unknown [n=1]), recruited from rehabilitation centres throughout the Netherlands. Because some centres only contributed to part of the study, different numbers of participants are presented for different aspects of the study. Parents and speech and language therapists (SLTs) classified the communication level using the CFCS. Kappa was used to determine the intra- and interrater reliability. Spearman's correlation coefficient was used to determine the association between CFCS level and spoken language comprehension, and Fisher's exact test was used to examine the association between the CFCS level and method of communication. RESULTS: Interrater reliability of the CFCS-NL between parents and SLTs was fair (r=0.54), between SLTs good (r=0.78), and the intrarater (SLT) reliability very good (r=0.85). The association between the CFCS and spoken language comprehension was strong for SLTs (r=0.63) and moderate for parents (r=0.51). There was a statistically significant difference between the CFCS level and the preferred method of communication of the child (p<0.01). Also, CFCS level classification showed a statistically significant difference between parents and SLTs (p<0.01). INTERPRETATION: These data suggest that the CFCS-NL is a valid and reliable clinical tool to classify everyday communication in children with CP. Preferably, professionals should classify the child's CFCS level in collaboration with the parents to acquire the most comprehensive information about the everyday communication of the child in various situations both with familiar and with unfamiliar partners. PMID- 26136154 TI - QiShenYiQi Pills, a compound in Chinese medicine, protects against pressure overload-induced cardiac hypertrophy through a multi-component and multi-target mode. AB - The present study aimed to explore the holistic mechanism for the antihypertrophic effect of a compound in Chinese medicine, QiShenYiQi Pills (QSYQ) and the contributions of its components to the effect in rats with cardiac hypertrophy (CH). After induction of CH by ascending aortic stenosis, rats were treated with QSYQ, each identified active ingredient (astragaloside IV, 3, 4 dihydroxy-phenyl lactic acid or notoginsenoside R1) from its 3 major herb components or dalbergia odorifera, either alone or combinations, for 1 month. QSYQ markedly attenuated CH, as evidenced by echocardiography, morphology and biochemistry. Proteomic analysis and western blot showed that the majority of differentially expressed proteins in the heart of QSYQ-treated rats were associated with energy metabolism or oxidative stress. Each ingredient alone or their combinations exhibited similar effects as QSYQ but to a lesser extent and differently with astragaloside IV and notoginsenoside R1 being more effective for enhancing energy metabolism, 3, 4-dihydroxy-phenyl lactic acid more effective for counteracting oxidative stress while dalbergia odorifera having little effect on the variables evaluated. In conclusion, QSYQ exerts a more potent antihypertrophic effect than any of its ingredients or their combinations, due to the interaction of its active components through a multi-component and multi target mode. PMID- 26136156 TI - Regional scale selenium loading associated with surface coal mining, Elk Valley, British Columbia, Canada. AB - Selenium (Se) concentrations in surface water downstream of surface mining operations have been reported at levels in excess of water quality guidelines for the protection of wildlife. Previous research in surface mining environments has focused on downstream water quality impacts, yet little is known about the fundamental controls on Se loading. This study investigated the relationship between mining practices, stream flows and Se concentrations using a SPAtially Referenced Regression On Watershed attributes (SPARROW) model. This work is part of a R&D program examining the influence of surface coal mining on hydrological and water quality responses in the Elk Valley, British Columbia, Canada, aimed at informing effective management responses. Results indicate that waste rock volume, a product of mining activity, accounted for roughly 80% of the Se load from the Elk Valley, while background sources accounted for roughly 13%. Wet years were characterized by more than twice the Se load of dry years. A number of variables regarding placement of waste rock within the catchments, length of buried streams, and the construction of rock drains did not significantly influence the Se load. The age of the waste rock, the proportion of waste rock surface reclaimed, and the ratio of waste rock pile side area to top area all varied inversely with the Se load from watersheds containing waste rock. These results suggest operational practices that are likely to reduce the release of Se to surface waters. PMID- 26136155 TI - Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT. AB - The alternative splicing of the tau gene, MAPT, generates six protein isoforms in the adult human central nervous system (CNS). Tau splicing is developmentally regulated and dysregulated in disease. Mutations in MAPT that alter tau splicing cause frontotemporal dementia (FTD) with tau pathology, providing evidence for a causal link between altered tau splicing and disease. The use of induced pluripotent stem cell (iPSC)-derived neurons has revolutionized the way we model neurological disease in vitro. However, as most tau mutations are located within or around the alternatively spliced exon 10, it is important that iPSC-neurons splice tau appropriately in order to be used as disease models. To address this issue, we analyzed the expression and splicing of tau in iPSC-derived cortical neurons from control patients and FTD patients with the 10 + 16 intronic mutation in MAPT. We show that control neurons only express the fetal tau isoform (0N3R), even at extended time points of 100 days in vitro. Neurons from FTD patients with the 10 + 16 mutation in MAPT express both 0N3R and 0N4R tau isoforms, demonstrating that this mutation overrides the developmental regulation of exon 10 inclusion in our in vitro model. Further, at extended time points of 365 days in vitro, we observe a switch in tau splicing to include six tau isoforms as seen in the adult human CNS. Our results demonstrate the importance of neuronal maturity for use in in vitro modeling and provide a system that will be important for understanding the functional consequences of altered tau splicing. PMID- 26136157 TI - Comparison of arsenic bioaccessibility in housedust and contaminated soils based on four in vitro assays. AB - Few studies have assessed As bioaccessibility in housedust using different in vitro assays and compared to those in contaminated soils. We determined As bioaccessibility in 24 housedust samples (4.48-38.2 mg kg(-1)) using SBRC, IVG, DIN, and PBET assays and they averaged 73, 68, 53, and 48% in the gastric phase and 26, 46, 55 and 43% in the intestinal phase of the 4 assays. The corresponding As bioaccessibility in 34 As-contaminated soils (22-6899 mg kg(-1)) were 34, 25, 22, and 22% in the gastric phase and 18, 19, 21, and 20% in the intestinal phase, which was 1.5-2.7 fold lower than those in housedust possibly due to differences in contamination sources and properties. Based on the gastric phase of SBRC assay, As bioaccessibility was 44-96% in housedust and 2.3-80% in soils. Variation in As bioaccessibility among assays was similar for housedust and soils, with SBRC assay providing the highest bioaccessibility in gastric phase. In intestinal phase, dissolved As was probably adsorbed onto precipitated iron oxides, causing a sharp decrease in As bioaccessibility by SBRC assay. Unlike SBRC assay, gastric constituents (pepsin, mucin, phosphate, and citrate) in other 3 assays inhibited As adsorption and/or enhanced As dissolution, leading to greater As bioaccessibility. The greater As bioaccessibility in housedust than soil suggests the potential of greater health risk from As exposure to housedust than soil. PMID- 26136158 TI - Importance of Understanding the Validity and Reliability of Visual Analog Scales for Rating of Personality. PMID- 26136159 TI - Krypton Adsorption on Zeolite-Templated Carbon and Anomalous Surface Thermodynamics. AB - Krypton adsorption was measured at eight temperatures between 253 and 433 K on a zeolite-templated carbon and two commercial carbons. The data were fitted using a generalized Langmuir isotherm model and thermodynamic properties were extracted. Differing from that on commercial carbons, krypton adsorption on the zeolite templated carbon is accompanied by an increasing isosteric enthalpy of adsorption, rising by up to 1.4 kJ mol(-1) as a function of coverage. This increase is a result of enhanced adsorbate-adsorbate interactions promoted by the ordered, nanostructured surface of the adsorbent. An assessment of the strength and nature of these adsorbate-adsorbate interactions is made by comparing the measured isosteric enthalpies of adsorption (and other thermodynamic quantities) to fundamental metrics of intermolecular interactions of krypton and other common gases. PMID- 26136160 TI - Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition toward Vinyl Gold Intermediate over Alkene. AB - A dual catalytic approach enlisting gold and iron synergy is described. This method offers readily access to substituted heterocycle aldehydes via oxygen radical addition to vinyl-gold intermediates under Fe catalyst assistance. This system shows good functional group compatibility for the generation of substituted oxazole, indole, and benzofuran aldehydes. Mechanistic evidence greatly supports selective radical addition to an activated vinyl-Au double bond over alkene. This unique discovery offers a new avenue with great potential to further extend the synthetic power and versatility of gold catalysis. PMID- 26136161 TI - Implications of Akt2/Twist crosstalk on breast cancer metastatic outcome. AB - Akt2 is a pivotal player in a complex web of signaling pathways controlling cell growth, proliferation, and survival. The deregulation or aberrations of Akt2 have been associated with tumor progression, metastatic spread, and, lastly, chemoresistance. The impairment of its activity has gained more attention because Akt2 is intertwined with a range of signaling paths, including the Phosphatidylinositol 3 kinase/Akt/Mammalian target of rapamycin (PI3K/mTOR) signaling axis, which are involved in macromolecules synthesis and metabolism. Here, we focus on Akt2 because of its involvement in the acquisition of stem cell like properties, responsible for invasiveness and chemoresistance, also promoted by Twist. We also suggest therapeutic strategies targeting Akt2 to overcome the drawbacks of current cancer therapies. PMID- 26136162 TI - Compound Passport Service: supporting corporate collection owners in open innovation. AB - A growing number of early discovery collaborative agreements are being put in place between large pharma companies and partners in which the rights for assets can reside with a partner, exclusively or jointly. Our corporate screening collection, like many others, was built on the premise that compounds generated in-house and not the subject of paper or patent disclosure were proprietary to the company. Collaborative screening arrangements and medicinal chemistry now make the origin, ownership rights and usage of compounds difficult to determine and manage. The Compound Passport Service is a dynamic database, managed and accessed through a set of reusable services that borrows from social media concepts to allow sample owners to take control of their samples in a much more active way. PMID- 26136163 TI - Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces. AB - The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high < SS/low = L/high < L/low). Thus, 5HTTLPR and prior trauma exposure demonstrated counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings. PMID- 26136165 TI - A new cube-based dodecanuclear cobalt(ii) cluster with azide and tetrazolate ligands exhibiting ferromagnetic ordering. AB - A new cubane-based Co(ii) compound, [Co(12)(5 PT)(6)(CO(3))(N(3))2(O)(4)(CH(3)O)(6)(H(2)O)(18)] (1) (5-HPT = 5-phenyl-1H tetrazole), was synthesized by reaction of 5-HPT, CoCl(2).6H(2)O and NaN(3) in a methanol solution. In 1, a Co(12) cluster based on three identical Co(4)O(2)(ON)(2) cubane units bridged by a MU(6)-carbonate ligand is linked by pi pi stacking interactions between phenylene groups, forming a 3D supramolecular structure. Magnetic investigations indicate that compound 1 exhibits long-range ferromagnetic ordering at about 9 K. The cube-based Co(12) clusters with MU(6) CO(3)(2-) bridges are unprecedented. PMID- 26136164 TI - Repeatability of hypoxia PET imaging using [18F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial. AB - PURPOSE: Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [(18)F]HX4 in patients with head and neck and lung cancer. METHODS: Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [(18)F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUVmax and SUVmean) were defined and the tumor-to background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient. RESULTS: All parameters of [(18)F]HX4 uptake were significantly correlated between scans: SUVmax (r = 0.958, p < 0.001), SUVmean (r = 0.946, p < 0.001), TBRmax (r = 0.962, p < 0.001) and HV1.2 (r = 0.995, p < 0.001). The relative coefficients of repeatability were 15 % (SUVmean), 17 % (SUVmax) and 17 % (TBRmax). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65 +/- 0.14. CONCLUSION: Repeated hypoxia PET scans with [(18)F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [(18)F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments. PMID- 26136166 TI - Tandem Chemoselective Suzuki-Miyaura Cross-Coupling Enabled by Nucleophile Speciation Control. AB - Control of boronic acid speciation is presented as a strategy to achieve nucleophile chemoselectivity in the Suzuki-Miyaura reaction. Combined with simultaneous control of oxidative addition and transmetalation, this enables chemoselective formation of two C-C bonds in a single operation, providing a method for the rapid preparation of highly functionalized carbogenic frameworks. PMID- 26136167 TI - Reply: To PMID 25500425. PMID- 26136168 TI - The Appropriate Timing and Dose of Obeticholic Acid in Patients With Primary Biliary Cirrhosis. PMID- 26136169 TI - Reply: To PMID 25398770. PMID- 26136170 TI - Reply: To PMID 25474251. PMID- 26136171 TI - Comparison of the effects of propofol and emulsified isoflurane alone or combined with dexmedetomidine on induction of anesthesia in dogs. AB - OBJECTIVE: To compare the respective effects of propofol and emulsified isoflurane administered alone and in combination with dexmedetomidine on the quality of induction of anesthesia, physiological variables and recovery in dogs. STUDY DESIGN: Prospective, randomized, experimental trial. ANIMALS: Thirty-six adult mixed-breed dogs. METHODS: Animals were randomly assigned to one of four induction protocols: propofol alone (group P); emulsified isoflurane alone (group EI); both propofol and dexmedetomidine (group PD), or both emulsified isoflurane and dexmedetomidine (group EID). Pulse rate (PR), respiratory rate (fR ), non invasive arterial blood pressure and arterial blood gases were measured at baseline, before induction, immediately after intubation (time 0), and at 5 minute intervals until the dog began to swallow and the trachea was extubated. The quality of induction and recovery, and degree of ataxia were scored by a single investigator unaware of group assignment. The durations of anesthesia and recovery, and the incidence of adverse events were recorded. RESULTS: There were no clinically significant differences among the groups in induction quality. Systolic arterial pressure was lower in EID compared with P at 5 minutes. PR and fR were lower in PD and EID compared with P after induction. The PaCO2 at 5 minutes was higher than at baseline in group P. Ataxia score was lower in EID than in P. Time from induction to extubation and time from extubation to sternal recumbency were lower in EID compared with PD. CONCLUSIONS AND CLINICAL RELEVANCE: There were no clinically significant differences among the groups in induction quality. In PD and EID, but not in P, PR and fR were decreased after induction. The EID combination resulted in smooth and rapid induction and recovery and thus may be useful clinically for induction of anesthesia. PMID- 26136172 TI - Generation of Tetracosahexaenoic Acid in Benthic Marine Organisms. AB - Tetracosahexaenoic acid (THA, 24:6n-3) has been shown to have the strongest ability to suppress accumulation of lipids in HepG2 cells among well-known n-3 highly unsaturated fatty acids, such as EPA and DHA. In this study, a method for mass production of THA was investigated using distributions of THA and DHA in thirty-two marine organisms, such as starfishes, right-eyed flounders, shellfishes, and sharks. The fatty acid composition of the marine organisms was analyzed using GC-FID and THA was detected in starfish, right-eyed flounder, and shark. Furthermore, the ratio of DHA and THA (DHA/THA) in each sample was calculated using chromatogram peak area of GC-FID, and the value was found to be lower than 1 in some starfishes. As a result, THA was thought to be synthesized in the starfishes. In contrast, the value of DHA/THA for right-eyed flounder and sharks was greater than 1. The THA accumulation in right-eyed flounder was considered to be because of the starfishes that the flounder consumes as part of its diet. DHA is synthesized from THA by beta-oxidation in peroxisomes, in the Sprecher's shunt. The high accumulation of THA observed in the flounder would be caused by the decreasing enzyme activation due to beta-oxidation in the peroxisomes of the starfishes. Understanding the differences in THA between aquatic species could also potentially allow us to understand why THA is generated in marine animals. PMID- 26136173 TI - Effects of Dietary Plant-Origin Glucosylceramide on Bowel Inflammation in DSS Treated Mice. AB - The effects of dietary plant-origin glucosylceramide (GlcCer) on symptoms similar to those of inflammatory bowel diseasewere investigated in dextran sulfate sodium salt (DSS)-treated mice. Dietary GlcCer suppressed decreases in body weight due to DSS administration. To determine its effects on the colon, we examined its surface under a microscope following toluidine blue staining. Dietary GlcCer decreased DSS-induced chorionic crypt injury and elevated myeloperoxidase levels. Moreover, dietary GlcCer significantly suppressed the production of cytokines by the intestinal mucosa. These results provide evidence for the suppression of DSS induced inflammation by dietary GlcCer. PMID- 26136174 TI - Decrease in Corneal Damage due to Benzalkonium Chloride by the Addition of Mannitol into Timolol Maleate Eye Drops. AB - We investigated the protective effects of mannitol on corneal damage caused by benzalkonium chloride (BAC), which is used as a preservative in commercially available timolol maleate eye drops, using rat debrided corneal epithelium and a human cornea epithelial cell line (HCE-T). Corneal wounds were monitored using a fundus camera TRC-50X equipped with a digital camera; eye drops were instilled into rat eyes five times a day after corneal epithelial abrasion. The viability of HCE-T cells was calculated by TetraColor One; and Escherichia coli (ATCC 8739) were used to measure antimicrobial activity. The reducing effects on transcorneal penetration and intraocular pressure (IOP) of the eye drops were determined using rabbits. The corneal wound healing rate and rate constant (kH), as well as cell viability, were higher following treatment with 0.005% BAC solution containing 0.5% mannitol than in the case BAC solution alone; the antimicrobial activity was approximately the same for BAC solutions with and without mannitol. In addition, the kH for rat eyes instilled with commercially available timolol maleate eye drops containing 0.5% mannitol was significantly higher than that for eyes instilled with timolol maleate eye drops without mannitol, and the addition of mannitol did not affect the corneal penetration or IOP reducing effect of the timolol maleate eye drops. A preservative system comprising BAC and mannitol may provide effective therapy for glaucoma patients requiring long-term treatment with anti-glaucoma agents. PMID- 26136175 TI - Synthesis and Heteroannulation of Pyridine and Related Heterocyclic Systems Having Surface and Biological Activities. AB - Possible approaches to the synthesis of functionalized, pyrazole, isoxazole, pyrimidine, pyridine and fused pyridine derivatives The sequence involves the heterocyclization of ethyl 3-oxo-2-(4-stearamidobenzoyl)butanoate (3) with appropriate reagents. Propoxylated of these heterocycles using propylene oxide to produce nonionic surface active agents having a long alkyl chain with molecular weight suitable for becoming an amphiphilic molecule with correct hydrophilic lypophilic balance which enhances solubility, biodegradability and hence lowers the toxicity to human beings and becomes environmentally friendly. The antimicrobial activity of the newly synthesized was examined and it was found that some of these compounds have similar or higher activity compared with commercial antibiotic drugs (sulphadiazine), which make them suitable for diverse applications like the manufacturing of drugs, pesticides, emulsifiers, cosmetics, etc. PMID- 26136176 TI - Competitive Solubilization of Cholesterol/Cholesteryl Oleate and Seven Species of Sterol/Stanol in Model Intestinal Solution System. AB - The addition of plant sterols/stanols (sterols or stanols) can reduce the solubilization of cholesterol in a model intestinal solution system. We studied the molecular structure of seven different sterols/stanols and the effect they had on the solubilization of cholesterol or cholesterol ester in a model intestinal solution. The differences in the molecular structures of the sterol/stanol species influenced their abilities to reduce the solubility of cholesterol in the competitive solubilization experiments. Cholestanol whose molecular structure resembled cholesterol was the most effective at reducing the solubilization of cholesterol and cholesterol ester, with the solubilities of cholesterol and cholesteryl oleate being 41% and 39% respectively of the values observed for the single solubilizate systems. beta-Sitosterol was also able to reduce the solubilities of cholesterol and cholesteryl oleate to 43% and 45% of those observed in a single solubilizate system. Both, stigmasterol and brassicasterol have an unsaturated double bond in a steroid side chain and did not exhibit major cholesterol-lowering effects. These results were reflected by the Gibbs free energy change values (DeltaG(0)) for solubilization, where the sterol/stanol species with cholesterol-lowering effects had similar or larger negative DeltaG(0) values than those observed for cholesterol. PMID- 26136177 TI - Radical-scavenging Activity and Antioxidative Effects of Olive Leaf Components Oleuropein and Hydroxytyrosol in Comparison with Homovanillic Alcohol. AB - Olive leaf has great potential as a natural antioxidant, and one of its major phenolic components is oleuropein. In this study, the antioxidant activity of oleuropein against oxygen-centered radicals was measured by examining its sparing effects on the peroxyl radical-induced decay of fluorescein and pyrogallol red, in comparison with related compounds. The antioxidant capacity of oleuropein against lipid peroxidation was also assessed through its effect on the free radical-induced oxidation of methyl linoleate in a micelle system. On a molar basis, oleuropein and hydroxytyrosol inhibited the decay of fluorescein for longer than both homovanillic alcohol and the vitamin-E mimic 2-carboxy-2,5,7,8 tetramethyl-6-chromanol (Trolox), but did not suppress pyrogallol red decay in a concentration-dependent manner. Measurement of the fluorescein decay period revealed that the stoichiometric number of oleuropein and hydroxytyrosol against peroxyl radicals was twice that of Trolox, which is substantially higher than expectations based on chemical structure. Oleuropein and hydroxytyrosol were also more effective than Trolox and homovanillic alcohol at suppressing the oxidation of methyl linoleate in the micelle system. Thus, both oleuropein and hydroxytyrosol exhibit high antioxidative activity against lipid peroxidation induced by oxygen-centered radicals, but the high reactivity of phenolic/catecholic radicals makes their mechanism of action complex. PMID- 26136178 TI - Sports physiotherapy advancing in New Zealand. PMID- 26136179 TI - Platelet-rich plasma does not enhance return to play in hamstring injuries: a randomised controlled trial. AB - BACKGROUND: To evaluate the efficacy of a single platelet-rich plasma (PRP) injection in reducing the return to sport duration in male athletes, following an acute hamstring injury. METHODS: A randomised, three-arm (double-blind for the injection arms), parallel-group trial, in which 90 professional athletes with MRI positive hamstring injuries were randomised to injection with PRP-intervention, platelet-poor plasma (PPP-control) or no injection. All received an intensive standardised rehabilitation programme. The primary outcome measure was time to return to play, with secondary measures including reinjury rate after 2 and 6 months. RESULTS: The adjusted HR for the PRP group compared with the PPP group was 2.29 (95% CI 1.30 to 4.04) p=0.004; for the PRP group compared with the no injection group 1.48 (95% CI 0.869 to 2.520) p=0.15, and for the PPP group compared with the no injection group 1.57 (95% CI 0.88 to -2.80) p=0.13. The adjusted difference for time to return to sports between the PRP and PPP groups was -5.7 days (95% CI -10.1 to -1.4) p=0.01; between the PRP and no injection groups -2.9 days (95% CI -7.2 to 1.4) p=0.189 and between the PPP and no injection groups 2.8 days (95% CI -1.6 to 7.2) p=0.210. There was no significant difference for the secondary outcome measures. No adverse effects were reported. CONCLUSIONS: Our findings indicate that there is no benefit of a single PRP injection over intensive rehabilitation in athletes who have sustained acute, MRI positive hamstring injuries. Intensive physiotherapy led rehabilitation remains the primary means of ensuring an optimal return to sport following muscle injury. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01812564. PMID- 26136180 TI - New Zealand sports physiotherapy code of conduct. PMID- 26136182 TI - Minimizing Errors in Breast Pathology: A Call for Action. PMID- 26136181 TI - Functional heterogeneity of calretinin-expressing neurons in the mouse superficial dorsal horn: implications for spinal pain processing. AB - KEY POINTS: The superficial spinal dorsal horn contains a heterogeneous population of neurons that process sensory inputs. Information on the properties of excitatory interneurons in this region is limited. As calretinin is a protein thought to be restricted to an excitatory population in this region, the aim of this study was to characterize calretinin-expressing neurons. Most calretinin cells (85%) exhibited large A-type potassium currents and delayed firing action potential discharge, and received strong excitatory synaptic input, whereas the remainder exhibited hyperpolarization-activated cation currents and low threshold T-type calcium currents, and tonic- or initial bursting firing patterns, and received weak excitatory synaptic input. These respective features are consistent with properties of excitatory and inhibitory interneuron populations in this region of the spinal cord. Our findings have resolved a previously unidentified population of inhibitory interneurons. Furthermore, the contrasting excitability patterns of excitatory and inhibitory calretinin-expressing neurons suggest that they play distinct roles in spinal sensory processing circuits. ABSTRACT: Neurons in the superficial dorsal horn (SDH) of the spinal cord play an important role in nociceptive, thermal, itch and light touch sensations. Excitatory interneurons comprise ~65% of all SDH neurons but surprisingly few studies have investigated their role in spinal sensory processing. Here we use a transgenic mouse to study putative excitatory SDH neurons that express the calcium binding protein calretinin (CR). Our immunocytochemical, morphological and electrophysiological analysis identified two distinct populations of CR-expressing neurons, which we termed 'Typical' and 'Atypical'. Typical CR-expressing neurons comprised ~85% of the population and exhibited characteristic excitatory interneuron properties including delayed firing discharge, large rapid A-type potassium currents, and central, radial or vertical cell morphologies. Atypical neurons exhibited properties consistent with inhibitory interneurons, including tonic firing or initial bursting discharge, Ih currents, and islet cell morphology. Although both Typical and Atypical CR-expressing neurons responded to noxious peripheral stimulation, the excitatory drive onto Typical CR-expressing neurons was much stronger. Furthermore, Atypical CR-expressing cells comprise at least two functionally distinct subpopulations based on their responsiveness to noxious peripheral stimulation and neurochemical profile. Together our data suggest CR expression is not restricted to excitatory neurons in the SDH. Under normal conditions, the contribution of 'Typical' excitatory CR-expressing neurons to overall SDH excitability may be limited by the presence of A-type potassium currents, which limit the effectiveness of their strong excitatory input. Their contribution may, however, be increased in pathological situations where A-type potassium currents are decreased. By contrast, 'Atypical' inhibitory neurons with their excitable phenotype but weak excitatory input may be more easily recruited during increased peripheral stimulation. PMID- 26136183 TI - Recurrent Corynebacterium kroppenstedtii Breast Abscess in a Young Asian Female. PMID- 26136184 TI - Epilepsy in patients with primary brain tumors: The impact on mood, cognition, and HRQOL. AB - BACKGROUND: A primary brain tumor (PBT) is often a fatal disease of the nervous system and has a serious impact on health-related quality of life (HRQOL). Presence of epilepsy and adverse reactions from tumor and epilepsy treatments may cause additional decline in HRQOL. OBJECTIVES: We aimed to study the impact of epileptic seizures on cognition, mood, and HRQOL in patients with brain tumor related epilepsy. MATERIALS AND METHOD: Patients were grouped on an ordinal scale according to epilepsy burden from none to severe based on the presence of epileptic seizures and seizure frequency: L1, no epilepsy; L2, with epilepsy, seizure-free in the last 6 months with antiepileptic drugs; and L3, with epilepsy, at least one seizure in the last 6 months with AEDs. Health-related quality of life was measured by Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Quality of Life in Epilepsy-31 (QOLIE-31) tools, cognition by the Montreal Cognitive Assessment (MoCA) tool and Frontal Assessment Battery (FAB), mood by the Hospital Anxiety and Depression Scale (HADS), activities of daily living (ADLs) by the Barthel Index (BI), and performance status by the Karnofsky Performance Status (KPS) scale in patients with primary brain tumors at least one month following neurosurgery with or without radiotherapy and chemotherapy. RESULTS: Eighty-one patients with a diagnosis of primary brain tumors were recruited. Sixty-eight percent of patients were diagnosed with primary brain tumor-related epilepsy, 50.61% patients had cognitive impairment, 33% had abnormal scores in the anxiety scale, and 34% had abnormal scores in the depression scale. There were no statistically significant differences in these scores among L1, L2, and L3 groups. There were statistically significant differences in duration of disease and KPS and BI scores between L1 and L3 groups. The L3 group has significantly longer duration of disease and scored low in both the BI and KPS scale when compared to the L1 group. All patients with primary brain tumors scored significantly low in FACT-Br 'physical well-being' (PWB) and 'emotional well-being' (EWB) and high in 'social well-being' (SWB) when compared to healthy controls. When scores of each group were individually compared to healthy controls, the L3 group showed the lowest scores in PWB, EWB, and 'functional well-being'. In SWB, L1 and L2 groups showed statistically significantly high scores when compared to normative data. The QOLIE-31 applied to groups with epilepsy showed statistically significantly lower scores in the L3 group when compared to the L2 group in 'cognitive' and 'social functioning' domains. On multivariate analysis, both poor performance status and frequency of seizures were found to be independent risk factors for poor HRQOL when FACT-Br mean scores were compared. Level of seizures was found to be an independent risk factor for poor HRQOL when QOLIE-31 scores were compared between L2 and L3 groups. DISCUSSION: Presence of brain tumors could be attributed to cognitive impairment irrespective of the presence of epilepsy in our cohort. High seizure burden is an independent risk factor for poor HRQOL in patients with primary brain tumors. The QOLIE-31 is a more sensitive tool than the FACT-Br because of the presence of a seizure-related questionnaire. PMID- 26136185 TI - Bacterial lipopolysaccharides form physically cross-linked, two-dimensional gels in the presence of divalent cations. AB - We established a bacterial membrane model with monolayers of bacterial lipopolysaccharides (LPS Re and LPS Ra) and quantified their viscoelastic properties by using an interfacial stress rheometer coupled to a Langmuir film balance. LPS Re monolayers exhibited purely viscous behaviour in the absence of calcium ions, while the same monolayers underwent a viscous-to-elastic transition upon compression in the presence of Ca(2+). Our results demonstrated for the first time that LPSs in bacterial outer membranes can form two-dimensional elastic networks in the presence of Ca(2+). Different from LPS Re monolayers, the LPS Ra monolayers showed a very similar rheological transition both in the presence and absence of Ca(2+), suggesting that longer saccharide chains can form 2D physical gels even in the absence of Ca(2+). By exposure of the monolayers to the antimicrobial peptide protamine, we could directly monitor the differences in resistance of bacterial membranes according to the presence of calcium. PMID- 26136186 TI - Frailty: a costly phenomenon in caring for elders with cognitive impairment. AB - OBJECTIVES: Dementia draws on a variety of public and private resources. There is increasing pressure to define the cost components in this area to improve resource allocation and accountability. The aim of this study was to characterize frailty in a group of cognitively impaired community-dwelling elders and evaluate its relationship with cost and resource utilization. METHODS: We assessed a cross sectional, convenient sample of 115 cognitively impaired patients of age >55 years who attended the National Memory Clinic in St James' University Hospital, a Trinity College-affiliated hospital in Dublin, Ireland. Participants had a clinical diagnosis of possible Alzheimer's disease or mild cognitive impairment. Frailty was measured using the biological syndrome model. Formal health and social care costs and daily informal caregiving costs were collected and the total costs of care estimated by applying the appropriate unit cost estimate for each resource activity. Stepwise regression models were constructed to establish the factors associated with increased care costs. RESULTS: Patient dependence, frailty and number of co-morbid illnesses explained 43.3% of the variance in observed daily informal care costs in dementia and cognitively impaired patients. Dependence was the sole factor retained in an optimal model explaining 19% of the variance in formal health and social care costs. CONCLUSION: Frailty retained a strong association with daily informal care costs even in the context of other known risk factors for increasing care costs. Interventions that reduce frailty as well as patient dependence on others may be associated with cost savings. PMID- 26136187 TI - A framework for prescription in exercise-oncology research. AB - The field of exercise-oncology has increased dramatically over the past two decades, with close to 100 published studies investigating the efficacy of structured exercise training interventions in patients with cancer. Of interest, despite considerable differences in study population and primary study end point, the vast majority of studies have tested the efficacy of an exercise prescription that adhered to traditional guidelines consisting of either supervised or home based endurance (aerobic) training or endurance training combined with resistance training, prescribed at a moderate intensity (50-75% of a predetermined physiological parameter, typically age-predicted heart rate maximum or reserve), for two to three sessions per week, for 10 to 60 min per exercise session, for 12 to 15 weeks. The use of generic exercise prescriptions may, however, be masking the full therapeutic potential of exercise treatment in the oncology setting. Against this background, this opinion paper provides an overview of the fundamental tenets of human exercise physiology known as the principles of training, with specific application of these principles in the design and conduct of clinical trials in exercise-oncology research. We contend that the application of these guidelines will ensure continued progress in the field while optimizing the safety and efficacy of exercise treatment following a cancer diagnosis. PMID- 26136188 TI - Creatinine and myoglobin are poor predictors of anaerobic threshold in colorectal cancer and health. AB - AIMS: Myoglobin is a haem protein produced in skeletal muscles. Serum concentrations of myoglobin have been proposed as a surrogate marker of muscle mass and function in both cachectic cancer patients and healthy non-cancer individuals. Creatinine, a metabolite of creatine phosphate, an energy store found in skeletal muscle, is produced at a constant rate from skeletal muscle. Urinary and plasma creatinine have been used in clinical practice as indicators of skeletal muscle mass in health and disease. Our study aimed to test the hypothesis that plasma myoglobin and creatinine concentration could accurately predict skeletal muscle mass and aerobic capacity in colorectal cancer (CRC) patients and matched healthy controls and thereby an indicative of aerobic performance. METHODS: We recruited 47 patients with CRC and matching number of healthy volunteers for this study. All participants had their body composition measured by dual-energy X-ray absorptiometry scan, aerobic capacity measured to anaerobic threshold (AT) by cardiopulmonary exercise testing and filled in objective questionnaires to assess the qualitative functions. This study was carried out in accordance with the Declaration of Helsinki, after approval by the local National Health Service (NHS) Research Ethics Committee. RESULTS: Age matched groups had similar serum myoglobin and creatinine concentrations in spite of differences in their aerobic capacity. AT was significantly lower in the CRC group compared with matched controls (1.18 +/- 0.44 vs. 1.41 +/- 0.71 L/min; P < 0.01). AT had significant correlation with lean muscle mass (LMM) among these groups, but myoglobin and creatinine had poor correlation with LMM and AT. CONCLUSIONS: Serum myoglobin is a poor predictor of muscle mass, and serum myoglobin and creatinine concentrations do not predict aerobic performance in CRC patients or healthy matched controls. PMID- 26136189 TI - Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved. AB - BACKGROUND: Cachexia and muscle atrophy are common consequences of cancer and chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake and direct effects on muscle proteolysis and protein synthesis are likely to mediate these effects, but the pathways leading to these events are not well understood. METHODS: We characterized molecular pathways involved in muscle atrophy induced by Lewis lung carcinoma (LLC) tumour implantation in c57/bl6 adult male mice and by administration of the chemotherapeutic agent cisplatin in mice and in C2C12 myotubes. The effects of exogenous ghrelin administration and its mechanisms of action were examined in these settings. RESULTS: Tumour implantation and cisplatin induced muscle atrophy by activating pro-inflammatory cytokines, p38 C/EBP-beta, and myostatin, and by down-regulating Akt, myoD, and myogenin, leading to activation of ubiquitin-proteasome-mediated proteolysis and muscle weakness. Tumour implantation also increased mortality. In vitro, cisplatin up regulated myostatin and atrogin-1 by activating C/EBP-beta and FoxO1/3. Ghrelin prevented these changes in vivo and in vitro, significantly increasing muscle mass (P < 0.05 for LLC and P < 0.01 for cisplatin models) and grip strength (P = 0.038 for LLC and P = 0.001 for cisplatin models) and improving survival (P = 0.021 for LLC model). CONCLUSION: Ghrelin prevents muscle atrophy by down regulating inflammation, p38/C/EBP-beta/myostatin, and activating Akt, myogenin, and myoD. These changes appear, at least in part, to target muscle cells directly. Ghrelin administration in this setting is associated with improved muscle strength and survival. PMID- 26136190 TI - Searching for a relevant definition of sarcopenia: results from the cross sectional EPIDOS study. AB - BACKGROUND: The diversity of definitions proposed for sarcopenia has been rarely tested in the same population, and so far, their clinical utilities for predicting physical difficulties could not be clearly understood. Our objective is to report the prevalence of sarcopenia and the characteristics of sarcopenic community-dwelling older women according to the different definitions of sarcopenia currently proposed. We also assessed these definitions for their incremental predictive value over currently standard predictors for some self reported difficulties in physical function and knee extension strength. METHODS: Cross-sectional analysis included data from 3025 non-disabled women aged 75 years or older without previous history of hip fracture from the inclusion visit of the EPIDemiologie de l'OSteoporose study. A total body composition evaluation was available for 2725 women. Sarcopenia was defined using six different definitions of sarcopenia based on different muscle mass, gait speed, and grip strength cut offs. Self-reported difficulties in physical function and knee extension strength were collected. Logistic regression and multiple linear regression models were built for each physical dysfunction, and the predictive capacity of sarcopenia (one model for each definition) was studied using the C-statistic, the net reclassification index, or adjusted R(2). RESULTS: The estimated prevalence of sarcopenia ranged from 3.3-20.0%. Only 85 participants (3.1%) were identified having sarcopenia according to all definitions. All definitions were, to some degree, associated with self-reported difficulties in physical function and knee extension strength, but none improved the predictive ability of the self-reported difficulties in physical function. Conversely, all definitions accounted for a small but significant amount of explained variation for predicting knee extension strength. CONCLUSIONS: Prevalence of sarcopenia varies widely depending on the definition adopted. Based on this research, the current definitions for sarcopenia does not substantially increment the predictive value of clinical characteristics of patients to predict self-reported physical difficulties and knee extension strength. PMID- 26136191 TI - Sarcopenia, obesity and sarcopenic obesity: effects on liver function and volume in patients scheduled for major liver resection. AB - BACKGROUND: Sarcopenia, obesity and sarcopenic obesity have been linked to impaired outcome after liver surgery. Preoperative liver function of sarcopenic, obese and sarcopenic-obese patients might be reduced, possibly leading to more post-operative morbidity. The aim of this study was to explore whether liver function and volume were influenced by body composition in patients undergoing liver resection. METHODS: In 2011 and 2012, all consecutive patients undergoing the methacetin breath liver function test were included. Liver volumetry and muscle mass analysis were performed using preoperative CT scans and Osirix((r)) software. Muscle mass and body-fat% were calculated. Predefined cut-off values for sarcopenia and the top two body-fat% quintiles were used to identify sarcopenia and obesity, respectively. Histologic assessment of the resected liver gave insight in background liver disease. RESULTS: A total number of 80 patients were included. Liver function and volume were comparable in sarcopenic(-obese) and non-sarcopenic(-obese) patients. Obese patients showed significantly reduced liver function [295 (95-508) vs. 358 (96-684) ug/kg/h, P = 0.018] and a trend towards larger liver size [1694 (1116-2685) vs. 1533 (869-2852) mL, P = 0.079] compared with non-obese patients. Weight (r = -0.40), body surface area (r = 0.32), estimated body-fat% (r = -0.43) and body mass index (r = -0.47) showed a weak but significant negative (all P < 0.05) correlation with liver function. Moreover, body-fat% was identified as an independent factor negatively affecting the liver function. CONCLUSION: Sarcopenia and sarcopenic obesity did not seem to influence liver size and function negatively. However, obese patients had larger, although less functional, livers, indicating dissociation of liver function and volume in these patients. PMID- 26136192 TI - Preserved muscle oxidative metabolic phenotype in newly diagnosed non-small cell lung cancer cachexia. AB - BACKGROUND: Cachexia augments cancer-related mortality and has devastating effects on quality of life. Pre-clinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype (OXPHEN) stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate the presence of muscle OXPHEN loss in newly diagnosed patients with lung cancer, especially in those with cachexia. METHODS: Quadriceps muscle biopsies of comprehensively phenotyped pre-cachectic (n = 10) and cachectic (n = 16) patients with non-small cell lung cancer prior to treatment were compared with healthy age-matched controls (n = 22). OXPHEN was determined by assessing muscle fibre type distribution (immunohistochemistry), enzyme activity (spectrophotometry), and protein expression levels of mitochondrial complexes (western blot) as well as transcript levels of (regulatory) oxidative genes (quantitative real-time PCR). Additionally, muscle fibre cross-sectional area (immunohistochemistry) and systemic inflammation (multiplex analysis) were assessed. RESULTS: Muscle fibre cross-sectional area was smaller, and plasma levels of interleukin 6 were significantly higher in cachectic patients compared with non-cachectic patients and healthy controls. No differences in muscle fibre type distribution or oxidative and glycolytic enzyme activities were observed between the groups. Mitochondrial protein expression and gene expression levels of their regulators were also not different. CONCLUSION: Muscle OXPHEN is preserved in newly diagnosed non-small cell lung cancer and therefore not a primary trigger of cachexia in these patients. PMID- 26136193 TI - Febuxostat improves outcome in a rat model of cancer cachexia. AB - BACKGROUND: Activity of xanthine oxidase is induced in cancer cachexia, and its inhibition by allopurinol or oxypurinol improves survival and reduces wasting in the Yoshida hepatoma cancer cachexia model. Here, we tested the effects of the second-generation xanthine oxidase inhibitor febuxostat compared with placebo in the same model as used previously by our group. METHODS: Wistar rats (~200 g) were treated daily with febuxostat at 5 mg/kg/day or placebo via gavage for a maximum of 17 days. Weight change, quality of life, and body composition were analysed. After sacrifice, proteasome activity in the gastrocnemius muscle was measured. Muscle-specific proteins involved in metabolism were analysed by western blotting. RESULTS: Treatment of the tumour-bearing rats with febuxostat led to a significantly improved survival compared with placebo (hazard ratio: 0.45, 95% confidence interval: 0.22-0.93, P = 0.03). Loss of body weight was reduced (-26.3 +/- 12.4 g) compared with placebo (-50.2 +/- 2.1 g, P < 0.01). Wasting of lean mass was attenuated (-12.7 +/- 10.8 g) vs. placebo (-31.9 +/- 2.1 g, P < 0.05). While we did not see an effect of febuxostat on proteasome activity at the end of the study, the pAkt/Akt ratio was improved by febuxostat (0.94 +/- 0.09) vs. placebo (0.41 +/- 0.05, P < 0.01), suggesting an increase in protein synthesis. CONCLUSIONS: Febuxostat attenuated cachexia progression and improved survival of tumour-bearing rats. PMID- 26136194 TI - Gender-specific differences in the development of sarcopenia in the rodent model of the ageing high-fat rat. AB - BACKGROUND: Sarcopenia is linked to functional impairments, loss of independence, and mortality. In the past few years, obesity has been established as being a risk factor for a decline in muscle mass and function. There are several molecular pathological mechanisms, which have been under discussion that might explain this relationship. However, most studies were conducted using male animals and for a short period of time. METHODS: In this study, the gender specific effect of long-term, high-fat content feeding in Sprague-Dawley rats was examined. Development of the quadriceps muscle of the animals was monitored in vivo using magnetic resonance. The results of these measurements and of the biochemical analysis of the aged muscle were compared. RESULTS: Surprisingly, only male but not female rats showed a decline in muscle cross-sectional area at 16 months of age as a result of a chronic oversupply of dietary fats. This loss of muscle mass could not be explained by either de-regulation of the anabolic Akt pathway or by up-regulation of the main ubiquitin ligases of muscle, MAFbx and MuRF-1. However, fusion of satellite cells to myotubes was induced by the high fat diet in male rats, possibly as a result of an increased need for compensatory regeneration processes. Caspase-3-dependent apoptosis induction, irrespective of diet, seems to be the major determinant of muscle decline during ageing in male but not female rats. CONCLUSION: Taken together, activation of the apoptosis inducing Caspase-3 seems to be the most important trigger for the age-related muscle loss. Male rats were more prone to the decline of muscle during ageing than female animals, which was further enforced by a long-term, high fat diet. PMID- 26136197 TI - Duret haemorrhage with full recovery. PMID- 26136196 TI - Experiences with TachoSil(r) in microneurosurgery. AB - BACKGROUND: We analyze our experience of using TachoSil(r) (Takeda Austria GmbH: Linz, Austria) in microneurosurgical procedures as a hemostat and also as a sealant to patch dural defects. MATERIALS AND METHODS: Beginning on January 1, 2012, we prospectively analyzed 100 consecutive surgeries where TachoSil was used. The patient group included 58 women (58 %) and 42 men (42 %); the mean age was 52 years (range, 3-85 years). Indications for surgery included removal of the tumor (53 cases; 53 %), clipping of the cerebral arterial aneurysm (31 cases; 31 %), and treatment of other pathologies, including AVM (four cases; 4 %), cavernomas (four cases; 4 %), spinal tumor, and traumatic subdural hematoma. Patients received postoperative care according to local neurosurgical department protocol, including a postoperative CT scan after each craniotomy. Primary assessment of the wound took place during the hospital stay as well as at discharge or transfer to a rehabilitation unit. Mean follow-up time was 4 months (range, 1-12 months). RESULTS: None of the patients developed postoperative hematoma after craniotomy or spinal procedure. At primary assessment during hospital stay, 93 patients (93 %) had had no wound-related problems over the normal course of healing. No case registered any liquor leak from the wound, and none of the patients showed any signs of allergic response related to TachoSil usage. At the last follow-up, 96 patients (96 %) experienced uneventful wound healing, and in four patients (4 %), superficial wound infection was successfully treated with oral antibiotics. CONCLUSIONS: Our results indicate that TachoSil can serve in neurosurgical practice at no additional risks. TachoSil proved to be an effective hemostat, sealant, and adhesive in either cranial or spinal procedures. PMID- 26136198 TI - Myolipoma and tethered cord in a complex sacral malformation in a 26-year-old patient. PMID- 26136199 TI - In vitro study of the specific interaction between poly(2-dimethylamino ethylmethacrylate) based polymers with platelets and red blood cells. AB - Poly(2-dimethylamino)ethyl methacrylate (PDMAEMA) is an attractive polycation frequently proposed as a non-viral vector for gene therapy. As expected for other cationic carriers, intravenous administration of PDMAEMA can result in its ionic complexation with various negatively charged domains found within the blood. To gain more insight into this polycation hemoreactivity, we followed the binding kinetics of a free form (FF) of fluorescein labelled PDMAEMA (Mn below 15 kDa) in normal human blood using flow cytometry. This in vitro study highlighted that platelets display higher affinity for this polycation compared to red blood cells (RBCs), with an adsorption isotherm characteristics of a specific saturable binding site. PDMAEMA (1-20 MUg/mL) exerted a concentration dependent proaggregant effect with a biphasic aggregation of washed platelets. Activation of platelets was also noticed in whole blood with the expression of P-selectin and fibrinogen on platelet surface. Although additional studies would be needed in order to elucidate the mechanism of PDMAEMA mediated activation of platelets, our manuscript provides important information on the hemoreactivity of FF PDMAEMA. PMID- 26136200 TI - Carrier-based dry powder inhalation: Impact of carrier modification on capsule filling processability and in vitro aerodynamic performance. AB - This study aims to investigate the effect of carrier characteristics and dosator capsule filling operation on the in vitro deposition of mixtures containing salbutamol sulphate (SS) and lactose and mannitol as model carrier materials. The carrier surfaces of lactose and mannitol were modified via wet decantation. The impact of the decantation process on the properties of carriers was investigated by laser diffraction, density and powder flow measurements, N2 physisorption, small and wide angle X-ray scattering (SWAXS) and scanning electron microscopy (SEM). Differences in carrier type and untreated and decanted materials were identified and the SAXS measurements proved to be a promising technology confirming the successful removal of fines. Adhesive carrier API mixtures with carrier-to-API ratio of 99:1 wt% were prepared, mixture homogeneity was tested and subsequently the mixtures were filled into capsules at different process settings. Finally, the influence of the decantation process on the in vitro performance of the adhesive mixtures was tested with a next generation impactor. For lactose, the decantation decreased the fine particle fraction (FPF) of SS, whereas the FPF of mannitol as a carrier was only affected by the capsule filling process. In summary, the DPI formulation based on untreated lactose, especially by capsule filling using a dosing chamber to powder layer (compression) ratio of 1:2, proved to be superior in terms of the dosing accuracy (RSD<0.8%) and the in vitro aerodynamic performance (FPF of 12%). PMID- 26136201 TI - Phthalimido-ferrocidiphenol cyclodextrin complexes: Characterization and anticancer activity. AB - Several ferrocenyl analogues of tamoxifen have already showed strong antiproliferative activity in experimental glioma models. Nevertheless, these compounds are very poorly soluble in water and an adapted formulation is needed. In this work, we have tailored and optimized methylated cyclodextrin soluble complexes of phthalimido-ferrocidiphenol for the first time. The complexes were characterized, and the optimized formulation was tested for in vitro efficacy and cell proliferation assays on U87, human glioblastoma cancer cells. Molecular modeling can provide accurate information about the inclusion process. The inclusion of all the moieties at the same time (i.e., ferrocene, phthalimidylpropyl, 2 phenols) is not possible due to the steric hindrance of the 1:4 system. The 1:3 systems are possible but do not seem very relevant. However, various 1:2 and 1:1 complexes are mostly present in aqueous solutions. Some experiments have confirmed our hypothesis. First, interactions between the phenol, phthalimidylpropyl and ferrocenyl groups have been observed in our NMR experiments. Second, the inclusion of phthalimidylpropyl was detected by UV-vis spectrophotometry with an apparent 1:1 interaction, which was observed through the Benesi-Hildebrand method. The complex is readily soluble in water and keeps its pharmacological activity against U87 tumor cells (IC50=0.028 +/- 0.007 MUM vs. 0.018 +/- 0.003 MUM for PhtFerr). PMID- 26136202 TI - Community Gender Norms Change as a Part of a Multilevel Approach to Sexual Health Among Married Women in Mumbai, India. AB - Inequitable gender norms in societies and communities negatively contribute to women's sexual and reproductive health. While the need for change in gender norms is well recognized, the task is highly challenging in terms of intervention design, implementation and assessment of impact. This paper describes a methodology for identification of gender norms, the design of community level intervention, community participation and the assessment of intervention impact in a low income, predominately Muslim community of 600,000 people in Mumbai, India. Formative research focused on in-depth interviews with women, men and couples yielding gender normative statements and assessment of community resources to facilitate change. A Gender Equity Scale (GES) based on this formative research was developed and administered annually for a three-year period to random, cross-sectional samples in the intervention and control communities, and to community based, non-governmental organizations (NGO) staff and Imams (religious leaders) in the intervention community. NGO staff disseminated gender oriented messages to their female constituency through their regular outreach activities and through special events and festivals in the community. Imams disseminated gender messages through lectures on social issues for men attending Friday prayers. The results showed that the NGO staff and Imams, assumed more gender equitable attitudes across time. The intervention was associated with a significant improvement in attitudes towards gender equity in the intervention relative to the control community. Men showed a dramatic change in more positive gender attitudes, while women lagged behind in their GES scores. The meaning of these results are explored and the implications assessed for the generalizability of the methodology for other countries, cultures and communities. PMID- 26136203 TI - Brachial-to-radial SBP amplification: implications of age and estimated central blood pressure from radial tonometry. AB - OBJECTIVES: The reference standard for noninvasive estimation of central blood pressure (BP) is radial tonometry calibrated using brachial SBP and DBP. Brachial to-radial-SBP amplification (B-R-SBPAmp) may introduce error into central BP estimation, but the magnitude of such amplification is uncertain. This study aimed to determine the magnitude and effect of ageing on B-R-SBPAmp; the effect of B-R-SBPAmp on radial tonometry estimated central SBP; and correlates of B-R SBPAmp. METHODS: Forty young (28 +/- 5 years) and 20 older (60 +/- 8 years) healthy participants underwent brachial and radial artery ultrasound to identify SBP from the first Doppler flow inflection during BP cuff deflation (first Korotkoff sound). Impedance cardiography, ultrasound, tonometry and anthropometric data were collected to explore B-R-SBPAmp correlates. RESULTS: Radial SBP was significantly higher than brachial SBP in younger (118 +/- 12 versus 110 +/- 10 mmHg; P < 0.001) and older (135 +/- 12 versus 121 +/- 11 mmHg; P < 0.001) participants. The magnitude of B-R-SBPAmp (radial minus brachial SBP) was higher in older than younger participants (14 +/- 7 versus 8 +/- 7 mmHg; P = 0.002), independent of sex and heart rate. Estimated central SBP was higher in both age groups when radial waveforms were recalibrated using radial (versus brachial) SBP (P < 0.001). The central SBP change relative to B-R-SBPAmp was associated with augmentation index (r = 0.739, P < 0.001), independent of age, sex and heart rate. Age, male sex and high-density lipoprotein each positively related to B-R-SBPAmp in multiple regression analysis (P < 0.05). CONCLUSION: Major B-R-SBPAmp occurs in healthy people and is higher with increasing age. Furthermore, B-R-SBPAmp contributes to underestimation of radial tonometry derived central SBP. PMID- 26136204 TI - Seventy years after the siege of Leningrad: does early life famine still affect cardiovascular risk and aging? AB - OBJECTIVE: To assess the cardiovascular health, markers of cardiovascular aging and telomere length in survivors of the siege of Leningrad, who were either born during the siege or lived in the besieged city in their early childhood. METHODS: Survivors of the Leningrad siege (n = 305, 64-81 years) and a control group of age and sex-matched individuals (n = 51, 67-82 years) were examined in terms of a observational retrospective cohort study. All participants were interviewed regarding risk factors, cardiovascular diseases, and therapy. Blood pressure measurement, anthropometry, echocardiography, and electrocardiography were performed according to standard guidelines. Fasting lipids and glucose were measured. Relative telomere length was measured by quantitative PCR, and the ratio of telomere repeat copy number to single gene copy number (T/S) was calculated for each DNA sample. RESULTS: Survivors had lower anthropometric parameters (height, weight, and BMI) and higher high-density lipoprotein level. There were no significant differences in the prevalence of cardiovascular diseases and target organ damage between groups. However, survivors had shorter telomere length: T/S ratio 0.44 (0.25; 0.64) vs. controls 0.91 (0.47; 1.13) (P < 0.0001), both in men and women, with clear association with the period of famine in early life. Exposure to famine in childhood and intrauterine period of life was associated with a higher prevalence of hypertension and shorter telomere length. CONCLUSION: Early-life famine, especially started in the intrauterine period and late childhood, may contribute to accelerated aging with telomere shortening in both sexes, but has no direct effect on the prevalence of cardiovascular diseases and risk factors after seven decades since exposure. PMID- 26136206 TI - Optimal home SBP targets for preventing the progression of diabetic nephropathy in patients with type 2 diabetes mellitus. AB - OBJECTIVES: Home blood pressure control can reduce the risk of increased urinary albumin excretion in patients with diabetes mellitus. However, the optimal home blood pressure targets to prevent the onset or progression of diabetic nephropathy are not well defined. METHODS: We performed a retrospective cohort study of 851 patients with type 2 diabetes mellitus. Logistic regression models were used to evaluate the correlations of home SBP levels with progression of diabetic nephropathy. RESULTS: During the follow-up of 2 years, 86 patients had progression of diabetic nephropathy. Adjusted odds ratios (95% confidence interval) for progression of diabetic nephropathy in patients with morning SBP of 120-129 mmHg [2.725 (1.074-6.917), P = 0.035], 130-139 mmHg [3.703 (1.519 9.031), P = 0.004] and in those with morning SBP equal or more than 140 mmHg [2.994 (1.182-7.581), P = 0.021] were significantly higher than that in those with morning SBP less than 120 mmHg in multiple logistic analyses. CONCLUSION: The preferable morning SBP targets might be less than 120 mmHg for preventing the onset or progression of diabetic nephropathy in patients with type 2 diabetes mellitus. PMID- 26136207 TI - Serum uric acid and the risk of cardiovascular and renal disease. AB - Substantial evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, chronic kidney disease (CKD) and cardiovascular diseases. This highlights the need for greater attention to serum uric acid levels when profiling patients, and suggests that the threshold above which uricemia is considered abnormal is 6 mg/dl, in light of the available evidence. Another important question is whether lowering serum uric acid can improve cardiovascular and renal outcomes, and what therapeutic mechanism of action could provide more clinical benefits to patients; the available literature shows a trend toward improvement associated with administration of urate-lowering drugs, in particular for the xanthine oxidase inhibitors. The demonstrated efficacy of urate-lowering therapy on outcomes other than gout flares leads to the consideration that treatment may be beneficial even in the absence of overt gout when hyperuricemia accompanies other clinical conditions, such as urate deposition, advanced CKD or cardiovascular risk factors. PMID- 26136205 TI - Home blood pressure monitoring: Australian Expert Consensus Statement. AB - Measurement of blood pressure (BP) by a doctor in the clinic has limitations that may result in an unrepresentative measure of underlying BP which can impact on the appropriate assessment and management of high BP. Home BP monitoring is the self-measurement of BP in the home setting (usually in the morning and evening) over a defined period (e.g. 7 days) under the direction of a healthcare provider. When it may not be feasible to measure 24-h ambulatory BP, home BP may be offered as a method to diagnose and manage patients with high BP. Home BP has good reproducibility, is well tolerated, is relatively inexpensive and is superior to clinic BP for prognosis of cardiovascular morbidity and mortality. Home BP can be used in combination with clinic BP to identify 'white coat' and 'masked' hypertension. An average home BP of at least 135/85 mmHg is an appropriate threshold for the diagnosis of hypertension. Home BP may also offer the advantage of empowering patients with their BP management, with benefits including increased adherence to therapy and lower achieved BP levels. It is recommended that, when feasible, home BP should be considered for routine use in the clinical management of hypertension. PMID- 26136208 TI - Burden of smoking among adults with COPD, chronic bronchitis, and emphysema in urban China. AB - OBJECTIVE: Tobacco, widely used in China, poses a major risk for chronic obstructive pulmonary disease (COPD). This study assessed health outcomes of COPD diagnosed smokers vs. never smokers and examined treatment patterns of patients attempting to quit smoking in urban China. METHODS: National Health and Wellness Survey (NHWS) 2010 and 2012 China data were analysed. Respondents self-reporting diagnosis with COPD, chronic bronchitis, or emphysema were categorised: quit attempters (current smokers 'trying to quit' or non-smokers 'in the process of quitting'), smokers (including quit attempters) and those who never smoked. Respondents reported smoking cessation treatment utilisation; health status: SF 36v2-based scores and SF-6D health utilities; Work Productivity and Activity Impairment questionnaire-based metrics; and resource utilisation. Regression modelling assessed health outcomes, controlling for covariates. RESULTS: Among 1421 (3.6%) diagnosed respondents, 51.6% never smoked and 35.5% smoked (of whom, 43.8% were attempting to quit). After adjustments, smokers vs. never smokers had significantly lower health utilities, lower mental/physical health status and greater absenteeism, presenteeism, overall work impairment, activity impairment, emergency room visits, hospitalisations and provider visits. Quit attempters were diagnosed an average 6.9 years (SD = 7.7) previously, with 25.3% reporting moderate/severe COPD. Most-reported main causes of COPD were: smoking (57.5%), illnesses/conditions (53.8%) and pollutants (44.3%). Among quit attempters, 82.8% smoked currently. Use of prescription cessation treatments was reported by 12.7%. CONCLUSIONS: Smokers experienced poorer health outcomes, reinforcing importance of prevention in mitigating disease burden. Among quit attempters, few reported using prescription cessation treatments. Given the high burden imposed by smoking in China, effective interventions may be beneficial. PMID- 26136209 TI - Unusual denaturation trajectory of bovine gamma globulin studied by fluorescence correlation spectroscopy. AB - Non-native and denatured states of proteins have received increasing attention because of their relevance to issues such as protein folding and stability. In this context, the pathway of polypeptide collapse and random coil formation in a denatured protein is a subject of much interest. Most proteins so far studied have shown monotonic expansion of their hydrodynamic radius (RH) in the presence of increasing concentration of chaotropes. We have studied GdnHCl-induced folding transitions and conformational states of a multi-domain protein, bovine gamma globulin, using fluorescence, circular dichroism and fluorescence correlation spectroscopy (FCS). FCS measurements showed that for gamma globulin, contrary to the observed trend, RH decreases with increasing GdnHCl concentration up to 3 M. At higher GdnHCl concentration, RH starts to increase but exhibits complicated behavior in the form of two sharp maxima at 4 M and 7 M. Further experiments suggest that the maximum at 4 M GdnHCl arises due to electrostatic interaction, whereas the one at 7 M GdnHCl corresponds to the usual expanded conformation due to denaturation. Beyond 7 M GdnHCl, RH decreases drastically and is shown to result from fragmentation of the protein caused by rupture of disulphide bonds by the high GdnHCl concentration. Our results demonstrate the capability of FCS in revealing intricate details of the unfolding trajectory that eludes conventional ensemble techniques such as fluorescence and CD. PMID- 26136210 TI - A metal-organic framework with immobilized Ag(i) for highly efficient desulfurization of liquid fuels. AB - A metal-organic framework immobilized with Ag(i) sites, namely, (Cr)-MIL-101 SO3Ag, was successfully developed as a highly efficient desulfurization adsorbent because of the strong binding of these Ag(i) sites for thiophene derivatives. PMID- 26136211 TI - CRISPR Content Correlates with the Pathogenic Potential of Escherichia coli. AB - Guide RNA molecules (crRNA) produced from clustered regularly interspaced short palindromic repeat (CRISPR) arrays, altogether with effector proteins (Cas) encoded by cognate cas (CRISPR associated) genes, mount an interference mechanism (CRISPR-Cas) that limits acquisition of foreign DNA in Bacteria and Archaea. The specificity of this action is provided by the repeat intervening spacer carried in the crRNA, which upon hybridization with complementary sequences enables their degradation by a Cas endonuclease. Moreover, CRISPR arrays are dynamic landscapes that may gain new spacers from infecting elements or lose them for example during genome replication. Thus, the spacer content of a strain determines the diversity of sequences that can be targeted by the corresponding CRISPR-Cas system reflecting its functionality. Most Escherichia coli strains possess either type I E or I-F CRISPR-Cas systems. To evaluate their impact on the pathogenicity of the species, we inferred the pathotype and pathogenic potential of 126 strains of this and other closely related species and analyzed their repeat content. Our results revealed a negative correlation between the number of I-E CRISPR units in this system and the presence of pathogenicity traits: the median number of repeats was 2.5-fold higher for commensal isolates (with 29.5 units, range 0-53) than for pathogenic ones (12.0, range 0-42). Moreover, the higher the number of virulence factors within a strain, the lower the repeat content. Additionally, pathogenic strains of distinct ecological niches (i.e., intestinal or extraintestinal) differ in repeat counts. Altogether, these findings support an evolutionary connection between CRISPR and pathogenicity in E. coli. PMID- 26136212 TI - Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes. AB - Myc controls the metabolic reprogramming that supports effector T cell differentiation. The expression of Myc is regulated by the T cell antigen receptor (TCR) and pro-inflammatory cytokines such as interleukin-2 (IL-2). We now show that the TCR is a digital switch for Myc mRNA and protein expression that allows the strength of the antigen stimulus to determine the frequency of T cells that express Myc. IL-2 signalling strength also directs Myc expression but in an analogue process that fine-tunes Myc quantity in individual cells via post transcriptional control of Myc protein. Fine-tuning Myc matters and is possible as Myc protein has a very short half-life in T cells due to its constant phosphorylation by glycogen synthase kinase 3 (GSK3) and subsequent proteasomal degradation. We show that Myc only accumulates in T cells exhibiting high levels of amino acid uptake allowing T cells to match Myc expression to biosynthetic demands. The combination of digital and analogue processes allows tight control of Myc expression at the population and single cell level during immune responses. PMID- 26136213 TI - The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. AB - There is a long-standing association between wound healing and cancer, with cancer often described as a "wound that does not heal". However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of Ras(G12V)-driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre-neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre-neoplastic cells and these interactions lead to increased proliferation of the pre-neoplastic cells. One of the wound-inflammation-induced trophic signals is prostaglandin E2 (PGE2). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome. PMID- 26136214 TI - The Elderly Spine Surgery Patient: Pre- and Intraoperative Management of Drug Therapy. AB - Spine surgery is one of the most common surgeries for adults greater than 65 years of age. Optimizing and caring for the elderly patient presenting for spine surgery requires planning and multidisciplinary input from surgeons, primary care physicians, and anesthesiologists. Controversies exist surrounding appropriate perioperative management of complicated chronic medication regimens and the ideal selection of intraoperative therapy for these patients. In this article we present an overview of the controversies anesthesiologists face as they work with the elderly patient's primary doctor and surgical team to achieve a safe perioperative course. Specifically, we discuss the interaction of geriatric physiology and pathophysiology with medications used in the perioperative period. While care of the geriatric spine surgery patient is nuanced, the anesthesiologist can work together with medical personnel, surgeons, and pharmacy to provide safe and effective care. PMID- 26136216 TI - Spontaneous splenic rupture during the recovery phase of dengue fever. AB - BACKGROUND: Spontaneous splenic rupture is a rare but known complication of dengue fever. Previously reported cases have occurred early during the course of the disease and most cases have led to a fatal outcome. Here we report a case of spontaneous splenic rupture in a patient with dengue fever, which occurred during the recovery phase of the illness. CASE PRESENTATION: A 28-year-old Sinhalese, Sri Lankan man presented with a history of fever, myalgia and vomiting of 4 days duration. Investigations revealed a diagnosis of dengue fever with no signs of plasma leakage. He was managed in the ward as per local protocol. During the recovery phase the patient developed severe abdominal distention with circulatory failure. Radiology revealed splenic rupture with massive amounts of abdominal free fluid. The patient was resuscitated and Emergency laparotomy with splenectomy was performed. The outcome was excellent with the patient making a complete recovery. CONCLUSION: Although splenic rupture is a known complication of dengue fever it may be manifested late in the disease process. A high degree of suspicion should be maintained and patients must be monitored even during the recovery phase of dengue fever. Early diagnosis and intervention can prevent mortality. PMID- 26136215 TI - Pharmacotherapy and Adherence Issues in Treating Elderly Patients with Glaucoma. AB - Glaucoma is a leading cause of visual morbidity throughout the world and is an age-related condition, the prevalence of which rises significantly with increasing age. Glaucoma, a condition affecting the optic nerve, has a variety of subtypes with multiple aetiological factors, the most important of which are intraocular pressure (IOP) and increasing age. Treatment by lowering of IOP is the only current method, for which there is evidence, by which the rate of progressive visual deterioration can be slowed or halted. Although there are surgical and laser treatments that are efficacious in lowering IOP, the most common manner in which patients with glaucoma control their IOP is with administration of daily topical ocular hypotensive drugs (eye drops). The variety of topical drugs utilised in the management of glaucoma all have the potential to have adverse effects and/or interactions with concomitant medications, many of which may be used for other age-related conditions. Adherence with appropriate medicines has a major effect on the outcome of medical conditions and this aspect applies to the management of glaucoma. There are certain specific issues that relate to the administration of topical agents, with respect to both adverse effects and adherence. Although many suspect poor adherence in elderly patients with glaucoma, relative to younger patients, adequate evidence for this is lacking. Furthermore, the manner by which adherence issues could be improved remains inadequately understood and poorly addressed. The aims of this article were to review, from a clinical perspective, the medical therapies currently used for glaucoma and discuss adherence issues with respect to the population of patients with glaucoma, who tend to be relatively elderly. PMID- 26136217 TI - The Blood-Brain Barrier Challenge for the Treatment of Brain Cancer, Secondary Brain Metastases, and Neurological Diseases. AB - Formation of metastases from various tumor entities in the brain is a major problem for the treatment of advanced cancer. We describe target molecules and tools for the delivery of small molecules or proteins across the blood-brain barrier (BBB), and the treatment of brain tumors and metastases with antibody related moieties. In addition, drugs preventing formation of metastases or interfering with the growth of established metastases are described, as well as pre-clinical metastasis models and corresponding clinical data. Furthermore, we discuss the delivery of effector proteins and antibody-based moieties fused with an antibody-based scaffold across the BBB in several model systems which might be applicable for the treatment of brain metastases. PMID- 26136218 TI - Combined Application of RGB Marking and Mass Spectrometric Imaging Facilitates Detection of Tumor Heterogeneity. AB - Cancer-cell heterogeneity dramatically influences treatment success, but escapes detection by classical histology. Mass-spectrometric imaging (MSI) represents a powerful method for visualizing the spatial distribution of proteins in tissue sections. Herein we asked whether MSI also facilitates detection of tumor heterogeneity. We first transduced the human neuroendocrine-carcinoma BON cell line following the red-green-blue (RGB) marking principle. RGB marking allows for specific color-coding of individual clones. Mice transplanted with RGB-marked BON cells developed liver tumors. We identified 16 primary tumors clearly distinguishable by histology and fluorescence imaging, but also based on a common tumor-specific signal pattern detected by MSI. Importantly, this pattern was clearly confined to tumor tissue while was absent from surrounding liver tissue. At the same time, we observed protein signals differentially present in a few or even single tumors. Since these signals were independent of RGB marking, they apparently reflected unique intrinsic protein-signal patterns of individual tumors. Thus, our data propose MSI as a tool for identifying divergent tissue by 'fingerprints' of protein signals, allowing not only for differentiation of tumor from healthy tissue but also detection of tumor heterogeneity. In conclusion, by visualizing tumor heterogeneity, MSI ideally complements microscopy-based methods. This might help to better understand tumor biology and develop future treatment strategies. PMID- 26136219 TI - High Frequency of JCV DNA Detection in Prostate Cancer Tissues. AB - BACKGROUND: Prostate cancer (PC) represents the most frequently diagnosed cancer in men. Exposure to infectious agents has been considered to induce prostatic inflammation and cancerous transformation. Controversial data exist concerning the role of the human polyomaviruses BK (BKV) and JC (JCV) in PC etiology. Therefore, a possible association between these polyomaviruses and PC was investigated. MATERIALS AND METHODS: Urine, blood and fresh prostatic tissue specimens were collected from 26 patients with PC. The presence of BKV and JCV, the possible non-coding control region (NCCR) variations and the genotyping analysis of viral protein 1 (VP1) of both viruses were assessed. RESULTS: Data showed a preferential viral re-activation in the urinary compartment and a statistically significant prevalence of JC viruria and of BKV in PC tissues. A BKV DDP-like NCCR sequence was isolated in two patients, whereas JCV NCCR was consistently of an archetypal structural organization. A prevalence of the European genotypes was observed for both viruses. CONCLUSION: Our data demonstrated the presence of JCV DNA in 14/24 (58.3%) cancerous prostatic tissue specimens, confirming the results obtained in a previous study, in which JCV has been defined as common inhabitant of the prostate, and opening the discussion about its potential role in PC. PMID- 26136220 TI - Proteomic Analysis Reveals Aberrant O-GlcNAcylation of Extracellular Proteins from Breast Cancer Cell Secretion. AB - BACKGROUND: O-GlcNAcylation is a unique intracellular protein modification; however, few extracellular O-GlcNAc-modified proteins have been discovered. We have previously demonstrated that many cellular proteins were aberrant in O GlcNAcylation in breast cancer tissues. In the present study, therefore, we investigated whether O-GlcNAc-modified proteins were abnormally secreted from breast cancer cells. MATERIALS AND METHODS: Intracellular and extracellular proteins were prepared from cell lysates of breast cancer cells (MCF-7 and MDA-MB 231) and normal breast cells (HMEC) and from their serum-free media (SFM), respectively. O-GlcNAcylation level was examined by immunoblotting. O-GlcNAc Modified proteins were identified using two-dimensional gel electrophoresis and Liquid Chromatography-tandem Mass Spectrometry. RESULTS: O-GlcNAcylation level was significantly increased in the extracellular compartment of both types of cancer cells compared to normal cells. Interestingly, O-GlcNAc patterns differed between intracellular and extracellular proteins. Proteomic analysis revealed that many O-GlcNAc spots in MCF-7 secretions were abnormally increased in comparison to those in HMEC secretions. Among these, transitional endoplasmic reticulum ATPase (TER ATPase) and heat-shock 70 kDa (HSP70) were confirmed to be O-GlcNAc-modified. The levels of O-GlcNAc-HSP70 and O-GlcNAc-TER ATPase were higher in SFM from MCF-7 cells than in that from HMEC. CONCLUSION: O-GlcNAcomic study of the extracellular compartments reveals aberrant O-GlcNAc-secreted proteins, which may be of interest as potential biomarkers in breast cancer. PMID- 26136221 TI - Over ten years of single-institution experience in percutaneous image-guided treatment of bone metastases from differentiated thyroid cancer. AB - OBJECTIVE: Percutaneous image-guided treatments (PIGT) are performed by interventional radiologists with a minimally invasive approach. Currently, very little published data on their outcomes are available and conclusions regarding their application are cautious. The aim of the present study was to review our experience in PIGT of bone metastases from thyroid cancer. MATERIALS AND METHODS: Institutional databases were reviewed to identify patients with differentiated thyroid cancer and bone metastases who received PIGT between October 2001 and April 2014. Complications, local evolution of the treated lesions, and overall survival (OS) were investigated. RESULTS: Twenty-five patients (12 male, 13 female) underwent 49 PIGT sessions consisting of cementoplasty (77.5%), cryoablation (14.3%) or radiofrequency ablation (8.2%). Most of the treated lesions (50/54, 92.6%) were symptomatic at the time of PIGT. Median follow-up after PIGT was 4.6 years. Local complete remission rate was 55.6%. Two complications (one major and one minor) were noted, but none of these were consistent with fractures or nervous system injuries. OS after PIGT was 71.6%, 66.8% and 60.1% at 1, 2 and 3 years, respectively. A difference in survival was observed between patients with metastatic bone involvement only at the time of first PIGT compared to those with multi-organ involvement (P = 0.03). CONCLUSIONS: Patients with bone metastases from differentiated thyroid cancer may benefit from PIGT. Although patients are usually referred for PIGT due to their symptomatic status, a more relevant "curative" role may exist for PIGT. Further prospective studies are needed to confirm this perception. PMID- 26136222 TI - Phenalenones: insight into the biosynthesis of polyketides from the marine alga derived fungus Coniothyrium cereale. AB - The marine alga-derived fungus Coniothyrium cereale is a prolific producer of phenalenones. These polyketides were shown to possess antimicrobial effects and inhibitory activity towards the protease human leucocyte elastase (HLE). The current study focused on the biosynthesis of eight different structural types of phenalenones, comprising the natural products rousselianone A' (1), coniosclerodin (3), cereolactam (12), cereoaldomine (15), and trypethelone (16). Solid agar cultures of C. cereale were used to follow up the incorporation of [1 (13)C] labeled acetate into these metabolites. Taking the respective mechanisms of polyketide metabolism into account, the labeling pattern was interpreted, thus providing a hypothesis for the biosynthetic formation of the phenalenones. The polyketide skeleton of the phenanthrene-based compound cereolactam is proposed to be formed through degradation of a heptaketide by loss of two carbon atoms. PMID- 26136224 TI - Stabilization of cubic Sr2FeMoO6 through topochemical reduction. AB - Sr2FeMoO6 has been extensively studied for application in spintronic devices. Through the topochemical de-intercalation of oxygen anions with metal hydride reduction, we demonstrate that the high temperature cubic phase is stabilized, at room temperature, whilst leaving the magnetic ordering intact. Synchrotron X-ray and neutron powder diffraction were used to characterize the structure and stoichiometry of the reduced oxide. PMID- 26136223 TI - Autocrine motility factor receptor promotes the proliferation of human acute monocytic leukemia THP-1 cells. AB - The aberrant activation of autocrine motility factor receptor (AMFR) has been implicated in several types of human cancer. The present study aimed to elucidate the effect of AMFR on the regulation of proliferation in an acute monocytic leukemia cell line, THP-1. THP-1 cells were transfected with AMFR-targeted small interfering (si)RNA and a plasmid encoding a truncated AMFR, AMFR-C, (pcDNA3.1 AMFR-C). The mRNA and protein levels of AMFR and the downstream targets, rho associated, coiled-coil containing protein kinase 2 (ROCK2), cyclin D1, and B cell lymphoma (Bcl)-2, were measured using reverse transcription-quantitatibe polymerase chain reaction and immunoblot analyses. The effects on cell cycle and apoptosis were investigated using flow cytometry. The present study successfully established the knockdown of AMFR and expression of AMFR-C in the THP-1 cells. Downregulation of AMFR induced cell cycle arrest at the G0/G1 phase, and increased apoptosis of the THP-1 cells (all P<0.05). The AMFR siRNA increased the percentage of early apoptotic cells between 3.88+/-1.43 and 19.58+/-4.29% (P<0.05). The expression levels of ROCK2, cyclin D1 and Bcl-2 were reduced by the downregulation of AMFR and enhanced by overexpression of AMFR-C. In conclusion, AMFR appears to be crucial for the proliferation of the THP-1 acute monocytic leukemia cell line. Therefore, AMFR may represent a potential target for the treatment of acute monocytic leukemia. PMID- 26136225 TI - Bayesian data assimilation provides rapid decision support for vector-borne diseases. AB - Predicting the spread of vector-borne diseases in response to incursions requires knowledge of both host and vector demographics in advance of an outbreak. Although host population data are typically available, for novel disease introductions there is a high chance of the pathogen using a vector for which data are unavailable. This presents a barrier to estimating the parameters of dynamical models representing host-vector-pathogen interaction, and hence limits their ability to provide quantitative risk forecasts. The Theileria orientalis (Ikeda) outbreak in New Zealand cattle demonstrates this problem: even though the vector has received extensive laboratory study, a high degree of uncertainty persists over its national demographic distribution. Addressing this, we develop a Bayesian data assimilation approach whereby indirect observations of vector activity inform a seasonal spatio-temporal risk surface within a stochastic epidemic model. We provide quantitative predictions for the future spread of the epidemic, quantifying uncertainty in the model parameters, case infection times and the disease status of undetected infections. Importantly, we demonstrate how our model learns sequentially as the epidemic unfolds and provide evidence for changing epidemic dynamics through time. Our approach therefore provides a significant advance in rapid decision support for novel vector-borne disease outbreaks. PMID- 26136226 TI - Control of vortex rings for manoeuvrability. AB - Manoeuvrability is critical to the success of many species. Selective forces acting over millions of years have resulted in a range of capabilities currently unmatched by machines. Thus, understanding animal control of fluids for manoeuvring has both biological and engineering applications. Within inertial fluid regimes, propulsion involves the formation and interaction of vortices to generate thrust. We use both volumetric and planar imaging techniques to quantify how jellyfish (Aurelia aurita) modulate vortex rings during turning behaviour. Our results show that these animals distort individual vortex rings during turns to alter the force balance across the animal, primarily through kinematic modulation of the bell margin. We find that only a portion of the vortex ring separates from the body during turns, which may increase torque. Using a fluorescent actin staining method, we demonstrate the presence of radial muscle fibres lining the bell along the margin. The presence of radial muscles provides a mechanistic explanation for the ability of scyphomedusae to alter their bell kinematics to generate non-symmetric thrust for manoeuvring. These results illustrate the advantage of combining imaging methods and provide new insights into the modulation and control of vorticity for low-speed animal manoeuvring. PMID- 26136227 TI - Tuning the phase of circadian entrainment. AB - The circadian clock coordinates daily physiological, metabolic and behavioural rhythms. These endogenous oscillations are synchronized with external cues ('zeitgebers'), such as daily light and temperature cycles. When the circadian clock is entrained by a zeitgeber, the phase difference psi between the phase of a clock-controlled rhythm and the phase of the zeitgeber is of fundamental importance for the fitness of the organism. The phase of entrainment psi depends on the mismatch between the intrinsic period tau and the zeitgeber period T and on the ratio of the zeitgeber strength to oscillator amplitude. Motivated by the intriguing complexity of empirical data and by our own experiments on temperature entrainment of mouse suprachiasmatic nucleus (SCN) slices, we present a theory on how clock and zeitgeber properties determine the phase of entrainment. The wide applicability of the theory is demonstrated using mathematical models of different complexity as well as by experimental data. Predictions of the theory are confirmed by published data on Neurospora crassa strains for different period mismatches tau - T and varying photoperiods. We apply a novel regression technique to analyse entrainment of SCN slices by temperature cycles. We find that mathematical models can explain not only the stable asymptotic phase of entrainment, but also transient phase dynamics. Our theory provides the potential to explore seasonal variations of circadian rhythms, jet lag and shift work in forthcoming studies. PMID- 26136228 TI - Novel sodium/lithium-ion anode material based on ultrathin Na2Ti2O4(OH)2 nanosheet. AB - Ultrathin Na2Ti2O4(OH)2 nanosheets of ~8 nm thickness were prepared by a facile method for the first time. The resulting material was also used as a conducting agent and binder-free anode, both for sodium-ion batteries and lithium-ion batteries, for the first time. The Na2Ti2O4(OH)2 nanosheets exhibited excellent Na/Li-ion storage performance. A long-term cycling performance of the ultrathin Na2Ti2O4(OH)2 nanosheets of 120 mA h g(-1) at ~10C was retained after 500 cycles for sodium-ion batteries, and 150 mA h g(-1) at ~1C was kept after 500 cycles for lithium-ion batteries. By comparison, the Na-ion storage performance is much better than the Li-ion storage performance of the Na2Ti2O4(OH)2 nanosheets anode, because of the existence of Na in the Na2Ti2O4(OH)2 host. PMID- 26136229 TI - The Sap Flow Dynamics and Response of Hedysarum scoparium to Environmental Factors in Semiarid Northwestern China. AB - Hedysarum scoparium is an important, fast-growing and drought-resistant shrub that has been extensively used for grassland restoration and preventing desertification in semiarid regions of northwestern China. The primary objective of this study was to investigate the diurnal and seasonal variations in stem sap flow (Js) and its relation to environmental factors. The stem heat balance method was applied to plants that were approximately 17 years old (with diameters of 25, 16, 13, and 9 mm at ground level and heights of 3.1, 1.8, 1.7 and 1.4 m) and growing under natural conditions. The vertical soil temperature profile (ST), soil surface heat flux (SoilG), volumetric soil moisture content (SWC) and meteorological variables such as solar radiation (Rn), air temperature (Ta), vapour pressure deficit (VPD), wind speed (Ws) relative humidity (RH) and precipitation (P) were simultaneously measured at a meteorological station on site. Results indicated that Js varied regularly during the diurnal and seasonal term. The nocturnal Js was substantial, with a seasonal variation similar to the patterns of daytime Js. The magnitude of Js changed considerably between sunny and rainy days. Redundancy (RDA) and Kendall's tau analysis suggested that daily Js in large plants was more sensitive to environmental factors, and the variation in daily Js during the growing season could be described by a multiple linear regression against environmental variables including Ta, VPD, Ws, RH, ST, and SoilG. While the nocturnal Js in smaller plants was more sensitive to meteorological factors. Ta, VPD, and Ws were significantly correlated with nighttime Js. The hourly nighttime sap flow rate of H. scoparium corresponded closely to Ta and VPD following a non-linear pattern. The results of this study can be used to estimate the transpiration of H. scoparium. PMID- 26136230 TI - Impairment of the Cellular Distribution and Stability of the Erythropoietin Receptor Through the Direct Targeting of Aristolochic Acid. AB - Aristolochic acid (AA) nephropathy is complicated with early onset and severe anemia. The molecular pathological mechanism of AA-induced anemia remains unclear. The aim of this study was to evaluate the putative pathological roles of the erythropoietin receptor (EPOR) in AA-induced anemia in both AA nephropathy zebrafish and cultured human renal tubular cells (HK2). Immunofluorescence staining experiments revealed that AA colocalizes with the EPOR in zebrafish embryos as well as in the cytoplasm of HK2 cells. After exogenous EPO stimulation, the EPOR was detected in the plasma membrane of HK cells. However, cotreatment with AA and EPO inhibited EPOR signaling and its membrane localization upon EPO stimulation. The results of studies with a protein synthesis inhibitor and a lysosome inhibitor revealed that AA accelerates the lysosomal degradation of EPOR. The molecular docking results suggest that AA may interact with the N-terminus of EPOR. Together with the results of light absorption and in vitro competition assays, we concluded that AA treatment impairs EPOR membrane localization, accelerates its lysosomal degradation, and consequently downregulates EPOR signaling by direct targeting. The results of this study may further detail the pathological mechanism of severe anemia complicated with AA nephropathy. PMID- 26136231 TI - The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene. AB - Exposure to the ubiquitous environmental contaminant trichloroethylene (TCE) is associated with cancer and non-cancer toxicity in both humans and rodents. Peroxisome proliferator-activated receptor-alpha (PPARalpha) is thought to be playing a role in liver toxicity in rodents through activation of the receptor by the TCE metabolite trichloroacetic acid (TCA). However, most studies using genetically altered mice have not assessed the potential for PPARalpha to alter TCE toxicokinetics, which may lead to differences in TCA internal doses and hence confound inferences as to the role of PPARalpha in TCE toxicity. To address this gap, male and female wild type (129S1/SvImJ), Pparalpha-null, and humanized PPARalpha (hPPARalpha) mice were exposed intragastrically to 400 mg/kg TCE in single-dose (2, 5 and 12 h) and repeat-dose (5 days/week, 4 weeks) studies. Interestingly, following either a single- or repeat-dose exposure to TCE, levels of TCA in liver and kidney were lower in Pparalpha-null and hPPARalpha mice as compared with those in wild type mice. Levels of trichloroethanol (TCOH) were similar in all strains. TCE-exposed male mice consistently had higher levels of TCA and TCOH in all tissues compared with females. Additionally, in both single- and repeat-dose studies, a similar degree of induction of PPARalpha-responsive genes was observed in liver and kidney of hPPARalpha and wild type mice, despite the difference in hepatic and renal TCA levels. Additional sex- and strain dependent effects were observed in the liver, including hepatocyte proliferation and oxidative stress, which were not dependent on TCA or TCOH levels. These data demonstrate that PPARalpha status affects the levels of the putative PPARalpha agonist TCA following TCE exposure. Therefore, interpretations of studies using Pparalpha-null and hPPARalpha mice need to consider the potential contribution of genotype-dependent toxicokinetics to observed differences in toxicity, rather than attributing such differences only to receptor-mediated toxicodynamic effects. PMID- 26136232 TI - Febuxostat pretreatment attenuates myocardial ischemia/reperfusion injury via mitochondrial apoptosis. AB - BACKGROUND: Febuxostat is a selective inhibitor of xanthine oxidase (XO). XO is a critical source of reactive oxygen species (ROS) during myocardial ischemia/reperfusion (I/R) injury. Inhibition of XO is therapeutically effective in I/R injury. Evidence suggests that febuxostat exerts antioxidant effects by directly scavenging ROS. The present study was performed to investigate the effects of febuxostat on myocardial I/R injury and its underlying mechanisms. METHODS: We utilized an in vivo mouse model of myocardial I/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of hypoxia/reoxygenation (H/R) injury. Mice were randomized into five groups: Sham, I/R (I/R + Vehicle), I/R + FEB (I/R + febuxostat), AL + I/R (I/R + allopurinol) and FEB (febuxostat), respectively. The I/R + FEB mice were pretreated with febuxostat (5 mg/kg; i.p.) 24 and 1 h prior to I/R. NRCs received febuxostat (1 and 10 uM) at 24 and 1 h before exposure to hypoxia for 3 h followed by reoxygenation for 3 h. Cardiac function, myocardial infarct size, serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), and myocardial apoptotic index (AI) were measured in order to ascertain the effects of febuxostat on myocardial I/R injury. Hypoxia/reperfusion (H/R) injury in NRCs was examined using MTT, LDH leakage assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The underlying mechanisms were determined by measuring ROS production, mitochondrial membrane potential (DeltaPsim), and expression of cytochrome c, cleaved caspases as well as Bcl-2 protein levels. RESULTS: Myocardial I/R led to an elevation in the myocardial infarct size, serum levels of CK and LDH, cell death and AI. Furthermore, I/R reduced cardiac function. These changes were significantly attenuated by pretreatment with febuxostat and allopurinol, especially by febuxostat. Febuxostat also protected the mitochondrial structure following myocardial I/R, inhibited H/R-induced ROS generation, stabilized the DeltaPsim, alleviated cytosolic translocation of mitochondrial cytochrome C, inhibited activation of caspase-3 and -9, upregulated antiapoptotic proteins and downregulated proapoptotic proteins. CONCLUSIONS: This study revealed that febuxostat pretreatment mediates the cardioprotective effects against I/R and H/R injury by inhibiting mitochondrial-dependent apoptosis. PMID- 26136233 TI - The Hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications. AB - The Hippo signalling is emerging as a tumour suppressor pathway whose function is regulated by an intricate network of intracellular and extracellular cues. Defects in the signal cascade lead to the activation of the Hippo transducers TAZ and YAP. Compelling preclinical evidence showed that TAZ/YAP are often aberrantly engaged in breast cancer (BC), where their hyperactivation culminates into a variety of tumour-promoting functions such as epithelial-to-mesenchymal transition, cancer stem cell generation and therapeutic resistance. Having acquired a more thorough understanding in the biology of TAZ/YAP, and the molecular outputs they elicit, has prompted a first wave of exploratory, clinically-focused analyses aimed at providing initial hints on the prognostic/predictive significance of their expression. In this review, we discuss oncogenic activities linked with TAZ/YAP in BC, and we propose clinical strategies for investigating their role as biomarkers in the clinical setting. Finally, we address the therapeutic potential of TAZ/YAP targeting and the modalities that, in our opinion, should be pursued in order to further study the biological and clinical consequences of their inhibition. PMID- 26136234 TI - Circularly Polarized Luminescence from Simple Organic Molecules. AB - This article aims to show the identity of "circularly polarized luminescent active simple organic molecules" as a new concept in organic chemistry due to the potential interest of these molecules, as availed by the exponentially growing number of research articles related to them. In particular, it describes and highlights the interest and difficulty in developing chiral simple (small and non aggregated) organic molecules able to emit left- or right-circularly polarized light efficiently, the efforts realized up to now to reach this challenging objective, and the most significant milestones achieved to date. General guidelines for the preparation of these interesting molecules are also presented. PMID- 26136235 TI - Suicide related ideation and behavior among Canadian gay and bisexual men: a syndemic analysis. AB - BACKGROUND: While several studies have demonstrated that gay and bisexual men are at increased risk of suicide less attention has been given to the processes that generate the inherent inequity with the mainstream population. This study tested whether syndemic theory can explain the excess suicide burden in a sample of Canadian gay and bisexual men. Syndemic theory accounts for co-occurring and mutually reinforcing epidemics suffered by vulnerable groups due to the effects of social marginalization. METHODS: This study used data from Sex Now 2011, a cross-sectional survey of Canadian gay and bisexual men (n = 8382). The analysis measured the extent to which anti-gay marginalization and several psychosocial health problems are associated with suicide related ideation and attempts. Since psychosocial health problems were hypothesized to have an additive effect on suicide related ideation and attempts, the analysis calculated the effect of accumulated psychosocial health problems on suicide behavior. RESULTS: Suicide ideation and attempts were positively associated with each individual marginalization indicator (verbal violence, physical violence, bullying, sexual violence and work discrimination) and psychosocial health problems (smoking, party drugs, depression, anxiety, STIs, HIV risk and HIV). Furthermore, prevalence of suicide ideation and attempts increased with each added psychosocial health problem. Those who reported 3 or more had 6.90 (5.47-8.70) times the odds of experiencing suicide ideation and 16.29 (9.82-27.02) times the odds of a suicide attempt compared to those with no psychosocial health problems. CONCLUSIONS: This investigation suggests that syndemics is a useful theory for studying suicide behavior among gay and bisexual men. Moreover, the findings highlight a need to address gay and bisexual men's health problems holistically and the urgent need to reduce this population's experience with marginalization and violence. PMID- 26136236 TI - Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. AB - Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host's ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat. PMID- 26136238 TI - Frac Sand Mines Are Preferentially Sited in Unzoned Rural Areas. AB - Shifting markets can cause unexpected, stochastic changes in rural landscapes that may take local communities by surprise. Preferential siting of new industrial facilities in poor areas or in areas with few regulatory restrictions can have implications for environmental sustainability, human health, and social justice. This study focuses on frac sand mining-the mining of high-quality silica sand used in hydraulic fracturing processes for gas and oil extraction. Frac sand mining gained prominence in the 2000s in the upper midwestern United States where nonmetallic mining is regulated primarily by local zoning. I asked whether frac sand mines were more commonly sited in rural townships without formal zoning regulations or planning processes than in those that undertook zoning and planning before the frac sand boom. I also asked if mine prevalence was correlated with socioeconomic differences across townships. After creating a probability surface to map areas most suitable for frac sand mine occurrence, I developed neutral landscape models from which to compare actual mine distributions in zoned and unzoned areas at three different spatial extents. Mines were significantly clustered in unzoned jurisdictions at the statewide level and in 7 of the 8 counties with at least three frac sand mines and some unzoned land. Subsequent regression analyses showed mine prevalence to be uncorrelated with land value, tax rate, or per capita income, but correlated with remoteness and zoning. The predicted mine count in unzoned townships was over two times higher than that in zoned townships. However, the county with the most mines by far was under a county zoning ordinance, perhaps indicating industry preferences for locations with clear, homogenous rules over patchwork regulation. Rural communities can use the case of frac sand mining as motivation to discuss and plan for sudden land-use predicaments, rather than wait to grapple with unfamiliar legal processes during a period of intense conflict. PMID- 26136237 TI - Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light. AB - Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo R2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal injury, and a prolonged sampling time, in order to better determine the connection between NF-L and DAI. PMID- 26136239 TI - Comparative Estimates of Crude and Effective Coverage of Measles Immunization in Low-Resource Settings: Findings from Salud Mesoamerica 2015. AB - Timely and accurate measurement of population protection against measles is critical for decision-making and prevention of outbreaks. However, little is known about how survey-based estimates of immunization (crude coverage) compare to the seroprevalence of antibodies (effective coverage), particularly in low resource settings. In poor areas of Mexico and Nicaragua, we used household surveys to gather information on measles immunization from child health cards and caregiver recall. We also collected dried blood spots (DBS) from children aged 12 to 23 months to compare crude and effective coverage of measles immunization. We used survey-weighted logistic regression to identify individual, maternal, household, community, and health facility characteristics that predict gaps between crude coverage and effective coverage. We found that crude coverage was significantly higher than effective coverage (83% versus 68% in Mexico; 85% versus 50% in Nicaragua). A large proportion of children (19% in Mexico; 43% in Nicaragua) had health card documentation of measles immunization but lacked antibodies. These discrepancies varied from 0% to 100% across municipalities in each country. In multivariate analyses, card-positive children in Mexico were more likely to lack antibodies if they resided in urban areas or the jurisdiction of De Los Llanos. In contrast, card-positive children in Nicaragua were more likely to lack antibodies if they resided in rural areas or the North Atlantic region, had low weight-for-age, or attended health facilities with a greater number of refrigerators. Findings highlight that reliance on child health cards to measure population protection against measles is unwise. We call for the evaluation of immunization programs using serological methods, especially in poor areas where the cold chain is likely to be compromised. Identification of within country variation in effective coverage of measles immunization will allow researchers and public health professionals to address challenges in current immunization programs. PMID- 26136241 TI - Observation of Body-Centered Cubic Gold Nanocluster. AB - The structure of nanoparticles plays a critical role in dictating their material properties. Gold is well known to adopt face-centered cubic (fcc) structure. Herein we report the first observation of a body-centered cubic (bcc) gold nanocluster composed of 38 gold atoms protected by 20 adamantanethiolate ligands and two sulfido atoms ([Au38S2(SR)20], where R=C10H15) as revealed by single crystal X-ray crystallography. This bcc structure is in striking contrast with the fcc structure of bulk gold and conventional Au nanoparticles, as well as the bi-icosahedral structure of [Au38(SCH2CH2Ph)24]. The bcc nanocluster has a distinct HOMO-LUMO gap of ca. 1.5 eV, much larger than the gap (0.9 eV) of the bi icosahedral [Au38(SCH2CH2Ph)24]. The unique structure of the bcc gold nanocluster may be promising in catalytic applications. PMID- 26136240 TI - From Structural Variation of Gene Molecules to Chromatin Dynamics and Transcriptional Bursting. AB - Transcriptional activation of eukaryotic genes is accompanied, in general, by a change in the sensitivity of promoter chromatin to endonucleases. The structural basis of this alteration has remained elusive for decades; but the change has been viewed as a transformation of one structure into another, from "closed" to "open" chromatin. In contradistinction to this static and deterministic view of the problem, a dynamical and probabilistic theory of promoter chromatin has emerged as its solution. This theory, which we review here, explains observed variation in promoter chromatin structure at the level of single gene molecules and provides a molecular basis for random bursting in transcription-the conjecture that promoters stochastically transition between transcriptionally conducive and inconducive states. The mechanism of transcriptional regulation may be understood only in probabilistic terms. PMID- 26136242 TI - A pH-Responsive Carrier System that Generates NO Bubbles to Trigger Drug Release and Reverse P-Glycoprotein-Mediated Multidrug Resistance. AB - Multidrug resistance (MDR) resulting from the overexpression of drug transporters such as P-glycoprotein (Pgp) increases the efflux of drugs and thereby limits the effectiveness of chemotherapy. To address this issue, this work develops an injectable hollow microsphere (HM) system that carries the anticancer agent irinotecan (CPT-11) and a NO-releasing donor (NONOate). Upon injection of this system into acidic tumor tissue, environmental protons infiltrate the shell of the HMs and react with their encapsulated NONOate to form NO bubbles that trigger localized drug release and serve as a Pgp-mediated MDR reversal agent. The site specific drug release and the NO-reduced Pgp-mediated transport can cause the intracellular accumulation of the drug at a concentration that exceeds the cell killing threshold, eventually inducing its antitumor activity. These results reveal that this pH-responsive HM carrier system provides a potentially effective method for treating cancers that develop MDR. PMID- 26136250 TI - Capacity building in physical activity and non-communicable disease prevention: a low-cost online training course can reach isolated practitioners. AB - Physical inactivity is the fourth most important risk factor contributing to global non-communicable disease (NCD) deaths, occurring in high-, middle- and low income countries. Building capacity in NCD prevention is a daunting task, and toward this end, an introductory open online course about physical activity (PA), exercise, and NCD prevention was developed. This was led by academics from the University of Sydney and the WHO Collaborating Centre for Physical Activity, Nutrition and Obesity. The course was designed to address the needs of participants from areas where geography and economy would often prevent them from participating in NCD training programs.Around 120 participants from four continents signed up for the six-week online course, with the greatest numbers from the host country (Australia) followed by participants from Pacific Island nations and from the Middle East. The course consisted of video lectures, quizzes, and online discussions facilitated by experts.More than a third of the participants fully completed the course, which received very positive participant evaluations. This also included completion of relevant quiz questions on each section of the PA course, and averaged over 70% correct responses.This successful online course has the potential to increase knowledge and skills about PA and prevention, as part of building global capacity in NCD prevention at low cost, and importantly within easy reach of potentially isolated practitioners. PMID- 26136249 TI - FXIa and platelet polyphosphate as therapeutic targets during human blood clotting on collagen/tissue factor surfaces under flow. AB - Factor XIIa (FXIIa) and factor XIa (FXIa) contribute to thrombosis in animal models, whereas platelet-derived polyphosphate (polyP) may potentiate contact or thrombin-feedback pathways. The significance of these mediators in human blood under thrombotic flow conditions on tissue factor (TF) -bearing surfaces remains inadequately resolved. Human blood (corn trypsin inhibitor treated [4 MUg/mL]) was tested by microfluidic assay for clotting on collagen/TF at TF surface concentration ([TF]wall) from ~0.1 to 2 molecules per MUm(2). Anti-FXI antibodies (14E11 and O1A6) or polyP-binding protein (PPXbd) were used to block FXIIa dependent FXI activation, FXIa-dependent factor IX (FIX) activation, or platelet derived polyP, respectively. Fibrin formation was sensitive to 14E11 at 0 to 0.1 molecules per um(2) and sensitive to O1A6 at 0 to 0.2 molecules per um(2). However, neither antibody reduced fibrin generation at ~2 molecules per um(2) when the extrinsic pathway became dominant. Interestingly, PPXbd reduced fibrin generation at low [TF]wall (0.1 molecules per um(2)) but not at zero or high [TF]wall, suggesting a role for polyP distinct from FXIIa activation and requiring low extrinsic pathway participation. Regardless of [TF]wall, PPXbd enhanced fibrin sensitivity to tissue plasminogen activator and promoted clot retraction during fibrinolysis concomitant with an observed PPXbd-mediated reduction of fibrin fiber diameter. This is the first detection of endogenous polyP function in human blood under thrombotic flow conditions. When triggered by low [TF]wall, thrombosis may be druggable by contact pathway inhibition, although thrombolytic susceptibility may benefit from polyP antagonism regardless of [TF]wall. PMID- 26136252 TI - Fused thiophene-pyrrole-containing ring systems up to a heterodecacene. AB - A new class of pi-conjugated polycyclic hydrocarbons that promises interesting electronic properties is presented. The synthesis and extension of the S,N heteroacene series consisting of only five-membered heterocyclic rings up to a very long, stable, and still soluble decacene SN10 is realized by multiple Pd catalyzed aminations of halogenated thiophene precursors as key reactions. These novel heteroacenes were characterized by optical spectroscopy and electrochemistry providing interesting structure-property relationships. Nearly complete bond-length equalization in the inner part of the conjugated backbone and an unusual herringbone packing in the solid state underline the structural features of these novel systems. PMID- 26136251 TI - Mice Lacking Pannexin 1 Release ATP and Respond Normally to All Taste Qualities. AB - Adenosine triphosphate (ATP) is required for the transmission of all taste qualities from taste cells to afferent nerve fibers. ATP is released from Type II taste cells by a nonvesicular mechanism and activates purinergic receptors containing P2X2 and P2X3 on nerve fibers. Several ATP release channels are expressed in taste cells including CALHM1, Pannexin 1, Connexin 30, and Connexin 43, but whether all are involved in ATP release is not clear. We have used a global Pannexin 1 knock out (Panx1 KO) mouse in a series of in vitro and in vivo experiments. Our results confirm that Panx1 channels are absent in taste buds of the knockout mice and that other known ATP release channels are not upregulated. Using a luciferin/luciferase assay, we show that circumvallate taste buds from Panx1 KO mice normally release ATP upon taste stimulation compared with wild type (WT) mice. Gustatory nerve recordings in response to various tastants applied to the tongue and brief-access behavioral testing with SC45647 also show no difference between Panx1 KO and WT. These results confirm that Panx1 is not required for the taste evoked release of ATP or for neural and behavioral responses to taste stimuli. PMID- 26136253 TI - [2+2] Photocycloaddition of Cinnamates in Flow and Development of a Thiourea Catalyst. AB - Cyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities. By utilizing a powerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flow on the dimerization of a range of cinnamate substrates. During the course of the study we also identified a bis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we show that carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers. PMID- 26136254 TI - Fabrication of Supported AuPt Alloy Nanocrystals with Enhanced Electrocatalytic Activity for Formic Acid Oxidation through Conversion Chemistry of Layer Deposited Pt(2+) on Au Nanocrystals. AB - The exploitation of nanoconfined conversion of Au- and Pt-containing binary nanocrystals for developing a controllable synthesis of surfactant-free AuPt nanocrystals with enhanced formic acid oxidation (FAO) activity is reported, which can be stably and evenly immobilized on various support materials to diversify and optimize their electrocatalytic performance. In this study, an atomic layer of Pt(2+) species is discovered to be spontaneously deposited in situ on the Au nanocrystal generated from a reverse-microemulsion solution. The resulting Au/Pt(2+) nanocrystal thermally transforms into a reduced AuPt alloy nanocrystal during the subsequent solid-state conversion process within the SiO2 nanosphere. The alloy nanocrystals can be isolated from SiO2 in a surfactant-free form and then dispersedly loaded on the carbon sphere surface, allowing for the production of a supported electrocatalyst that exhibits much higher FAO activity than commercial Pt/C catalysts. Furthermore, by involving Fe3O4 nanocrystals in the conversion process, the AuPt alloy nanocrystals can be grown on the oxide surface, improving the durability of supported metal catalysts, and then uniformly loaded on a reduced graphene oxide (RGO) layer with high electroconductivity. This produces electrocatalytic AuPt/Fe3O4/RGO nanocomposites whose catalyst-oxide-graphene triple-junction structure provides improved electrocatalytic properties in terms of both activity and durability in catalyzing FAO. PMID- 26136255 TI - The external PASTA domain of the essential serine/threonine protein kinase PknB regulates mycobacterial growth. AB - PknB is an essential serine/threonine protein kinase required for mycobacterial cell division and cell-wall biosynthesis. Here we demonstrate that overexpression of the external PknB_PASTA domain in mycobacteria results in delayed regrowth, accumulation of elongated bacteria and increased sensitivity to beta-lactam antibiotics. These changes are accompanied by altered production of certain enzymes involved in cell-wall biosynthesis as revealed by proteomics studies. The growth inhibition caused by overexpression of the PknB_PASTA domain is completely abolished by enhanced concentration of magnesium ions, but not muropeptides. Finally, we show that the addition of recombinant PASTA domain could prevent regrowth of Mycobacterium tuberculosis, and therefore offers an alternative opportunity to control replication of this pathogen. These results suggest that the PknB_PASTA domain is involved in regulation of peptidoglycan biosynthesis and maintenance of cell-wall architecture. PMID- 26136257 TI - Is Hyperuricemia Overlooked when Treating Pediatric Tuberculosis Patients with Pyrazinamide? AB - The treatment of tuberculosis (TB) requires long-term multiple drug use. Hyperuricemia is frequently reported in adults, but there are few data for the pediatric population. This study aimed to review drug-related side effects in pediatric patients that received treatment for TB. Patients with active TB undergoing treatment were followed for drug-related side effects. During the 7 year period, 23 patients with a mean age of 7.9 +/- 4.66 years were treated. Drug related side effects were observed in 14 patients. Hyperuricemia occurred in 12 of the 14 patients, vs. hepatotoxicity in 2. In all, eight of the patients with hyperuricemia had >=2 episodes during pyrazinamide (PZA) therapy. Based on these findings, we devised an algorithm that could be used for the management of hyperuricemia in patients receiving PZA because of TB, and recommend that hyperuricemia be closely monitored during PZA therapy. PMID- 26136256 TI - Induced pluripotent stem cell technology for modelling and therapy of cerebellar ataxia. AB - Induced pluripotent stem cell (iPSC) technology has emerged as an important tool in understanding, and potentially reversing, disease pathology. This is particularly true in the case of neurodegenerative diseases, in which the affected cell types are not readily accessible for study. Since the first descriptions of iPSC-based disease modelling, considerable advances have been made in understanding the aetiology and progression of a diverse array of neurodegenerative conditions, including Parkinson's disease and Alzheimer's disease. To date, however, relatively few studies have succeeded in using iPSCs to model the neurodegeneration observed in cerebellar ataxia. Given the distinct neurodevelopmental phenotypes associated with certain types of ataxia, iPSC-based models are likely to provide significant insights, not only into disease progression, but also to the development of early-intervention therapies. In this review, we describe the existing iPSC-based disease models of this heterogeneous group of conditions and explore the challenges associated with generating cerebellar neurons from iPSCs, which have thus far hindered the expansion of this research. PMID- 26136258 TI - A Combination of Moyamoya Pattern and Cerebral Venous Sinus Thrombosis: A Case of Tubercular Vasculopathy. AB - BACKGROUND: Moyamoya vasculopathy, arising secondary to tubercular meningitis (TBM) is unusual. There have also been a few reports of cerebral venous sinus thrombosis (CVST) in TBM. A case of TBM, complicated simultaneously by Moyamoya syndrome and CVST, is being presented here. CASE: A 1-year-old girl presented with febrile encephalopathy, vomiting, seizures and left hemiparesis. Cerebrospinal fluid analysis was suggestive of TBM. Extensive infarcts were noted in the magnetic resonance imaging, involving right middle cerebral artery (MCA), anterior cerebral artery and the left MCA. Magnetic resonance venogram revealed left transverse venous sinus thrombosis and magnetic resonance angiography showed bilateral moyamoya pattern of arteriopathy. Patient was started on antitubercular therapy and low molecular weight heparin. CONCLUSIONS: Early vascular involvement affecting both arterial and venous structures has not hitherto been reported in CNS tuberculosis. Early recognition of secondary complications of CNS tuberculosis is crucial to prevent the morbidity and mortality associated with TBM. PMID- 26136260 TI - Si=Si Double Bonds: Synthesis of an NHC-Stabilized Disilavinylidene. AB - An efficient two-step synthesis of the first NHC-stabilized disilavinylidene (Z) (SIdipp)Si=Si(Br)Tbb (2; SIdipp=C[N(C6H3-2,6-iPr2)CH2]2, Tbb=C6H2-2,6 [CH(SiMe3)2]2-4-tBu, NHC=N-heterocyclic carbene) is reported. The first step of the procedure involved a 2:1 reaction of SiBr2(SIdipp) with the 1,2 dibromodisilene (E)-Tbb(Br)Si=Si(Br)Tbb at 100 degrees C, which afforded selectively an unprecedented NHC-stabilized bromo(silyl)silylene, namely SiBr(SiBr2Tbb)(SIdipp) (1). Alternatively, compound 1 could be obtained from the 2:1 reaction of SiBr2(SIdipp) with LiTbb at low temperature. 1 was then selectively reduced with C8K to give the NHC-stabilized disilavinylidene 2. Both low-valent silicon compounds were comprehensively characterized by X-ray diffraction analysis, multinuclear NMR spectroscopy, and elemental analyses. Additionally, the electronic structure of 2 was studied by various quantum chemical methods. PMID- 26136259 TI - Chemical Evolution of a Bacterial Proteome. AB - We have changed the amino acid set of the genetic code of Escherichia coli by evolving cultures capable of growing on the synthetic noncanonical amino acid L beta-(thieno[3,2-b]pyrrolyl)alanine ([3,2]Tpa) as a sole surrogate for the canonical amino acid L-tryptophan (Trp). A long-term cultivation experiment in defined synthetic media resulted in the evolution of cells capable of surviving Trp->[3,2]Tpa substitutions in their proteomes in response to the 20,899 TGG codons of the E. coli W3110 genome. These evolved bacteria with new-to-nature amino acid composition showed robust growth in the complete absence of Trp. Our experimental results illustrate an approach for the evolution of synthetic cells with alternative biochemical building blocks. PMID- 26136261 TI - Pulmonary Codelivery of Doxorubicin and siRNA by pH-Sensitive Nanoparticles for Therapy of Metastatic Lung Cancer. AB - A pulmonary codelivery system that can simultaneously deliver doxorubicin (DOX) and Bcl2 siRNA to the lungs provides a promising local treatment strategy for lung cancers. In this study, DOX is conjugated onto polyethylenimine (PEI) by using cis-aconitic anhydride (CA, a pH-sensitive linker) to obtain PEI-CA-DOX conjugates. The PEI-CA-DOX/siRNA complex nanoparticles are formed spontaneously via electrostatic interaction between cationic PEI-CA-DOX and anionic siRNA. The drug release experiment shows that DOX releases faster at acidic pH than at pH 7.4. Moreover, PEI-CA-DOX/Bcl2 siRNA complex nanoparticles show higher cytotoxicity and apoptosis induction in B16F10 cells than those treated with either DOX or Bcl2 siRNA alone. When the codelivery systems are directly sprayed into the lungs of B16F10 melanoma-bearing mice, the PEI-CA-DOX/Bcl2 siRNA complex nanoparticles exhibit enhanced antitumor efficacy compared with the single delivery of DOX or Bcl2 siRNA. Compared with systemic delivery, most drug and siRNA show a long-term retention in the lungs via pulmonary delivery, and a considerable number of the drug and siRNA accumulate in tumor tissues of lungs, but rarely in normal lung tissues. The PEI-CA-DOX/Bcl2 siRNA complex nanoparticles are promising for the treatment of metastatic lung cancer by pulmonary delivery with low side effects on the normal tissues. PMID- 26136262 TI - Functional characterization of the homeodomain leucine zipper I transcription factor AtHB13 reveals a crucial role in Arabidopsis development. AB - AtHB13 is a homeodomain leucine zipper I transcription factor whose function in development is largely unknown. AtHB13 and AtHB23 mutant and silenced lines were characterized by expression studies, reciprocal crosses, complementation, molecular analyses, and developmental phenotypes. The athb13-1 and athb13-2 mutants, athb23 silenced, and athb13/athb23 double-silenced plants exhibited faster elongation rates of their inflorescence stems, whereas only athb13-1 and the double-knockdown athb13/athb23 exhibited shorter siliques, fewer seeds, and unfertilized ovules compared with the wild type (WT). The cell sizes of mutant and WT plants were similar, indicating that these transcription factors probably affect cell division. Reciprocal crosses between athb13-1 and the WT genotype indicated that the silique defect was male specific. Pollen hydration assays indicated that the pollen grains of the athb13-1 mutant were unable to germinate on stigmas. AtHB23-silenced plants exhibited normal siliques, whereas double knockdown athb13/athb23 plants were similar to athb13-1 plants. Both AtHB13 and AtHB23 were able to rescue the abnormal silique phenotype. AtHB23 was upregulated in athb13-2 plants, whereas its transcript levels in athb13-1 mutants were not significantly increased. Transcriptome analysis comparing athb13-1 and WT inflorescences revealed that a large number of genes, including several involved in pollen coat formation, are regulated by AtHB13. Finally, athb13-1 complementation with mutated versions of AtHB13 confirmed that two different tryptophans in its C terminus are essential. We conclude that AtHB13 and AtHB23 play independent, negative developmental roles in stem elongation, whereas only AtHB13 is crucial for pollen germination. Furthermore, AtHB23, which does not normally exert a functional role in pollen, can act as a substitute for AtHB13. PMID- 26136263 TI - Guanine nucleotide exchange factor 2 for Rab5 proteins coordinated with GLUP6/GEF regulates the intracellular transport of the proglutelin from the Golgi apparatus to the protein storage vacuole in rice endosperm. AB - Rice glutelin polypeptides are initially synthesized on the endoplasmic reticulum (ER) membrane as a proglutelin, which are then transported to the protein storage vacuole (PSV) via the Golgi apparatus. Rab5 and its cognate activator guanine nucleotide exchange factor (GEF) are essential for the intracellular transport of proglutelin from the Golgi apparatus to the PSV. Results from previous studies showed that the double recessive type of glup4/rab5a and glup6/gef mutant accumulated much higher amounts of proglutelin than either parent line. The present study demonstrates that the double recessive type of glup4/rab5a and glup6/gef mutant showed not only elevated proglutelin levels and much larger paramural bodies but also reduced the number and size of PSVs, indicating a synergistic mutation effect. These observations led us to the hypothesis that other isoforms of Rab5 and GEF also participate in the intracellular transport of rice glutelin. A database search identified a novel guanine nucleotide exchange factor, Rab5-GEF2. Like GLUP6/GEF, Rab5-GEF2 was capable of activating Rab5a and two other Rab5 isoforms in in vitro GTP/GDP exchange assays. GEF proteins consist of the helical bundle (HB) domain at the N-terminus, Vps9 domain, and a C terminal region. By the deletion analysis of GEFs, the HB domain was found essential for the activation of Rab5 proteins. PMID- 26136264 TI - Comparative studies of mitochondrial proteomics reveal an intimate protein network of male sterility in wheat (Triticum aestivum L.). AB - Plant male sterility has often been associated with mitochondrial dysfunction; however, the mechanism in wheat (Triticum aestivum L.) has not been elucidated. This study set out to probe the mechanism of physiological male sterility (PHYMS) induced by the chemical hybridizing agent (CHA)-SQ-1, and cytoplasmic male sterility (CMS) of wheat at the proteomic level. A total of 71 differentially expressed mitochondrial proteins were found to be involved in pollen abortion and further identified by MALDI-TOF/TOF MS (matrix-assisted laser desorption/ionization-time of fight/time of flight mass spectrometry). These proteins were implicated in different cellular responses and metabolic processes, with obvious functional tendencies toward the tricarboxylic acid cycle, the mitochondrial electron transport chain, protein synthesis and degradation, oxidation stress, the cell division cycle, and epigenetics. Interactions between identified proteins were demonstrated by bioinformatics analysis, enabling a more complete insight into biological pathways involved in anther abortion and pollen defects. Accordingly, a mitochondria-mediated male sterility protein network in wheat is proposed; this network was further confirmed by physiological data, RT PCR (real-time PCR), and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) assay. The results provide intriguing insights into the metabolic pathway of anther abortion induced by CHA-SQ-1 and also give useful clues to identify the crucial proteins of PHYMS and CMS in wheat. PMID- 26136265 TI - Mitogen-activated protein kinase kinase 5 (MKK5)-mediated signalling cascade regulates expression of iron superoxide dismutase gene in Arabidopsis under salinity stress. AB - Superoxide dismutases (SODs) are involved in plant adaptive responses to biotic and abiotic stresses but the upstream signalling process that modulates their expression is not clear. Expression of two iron SODs, FSD2 and FSD3, was significantly increased in Arabidopsis in response to NaCl treatment but blocked in transgenic MKK5-RNAi plant, mkk5. Using an assay system for transient expression in protoplasts, it was found that mitogen-activated protein kinase kinase 5 (MKK5) was also activated in response to salt stress. Overexpression of MKK5 in wild-type plants enhanced their tolerance to salt treatments, while mkk5 mutant exhibited hypersensitivity to salt stress in germination on salt containing media. Moreover, another kinase, MPK6, was also involved in the MKK5 mediated iron superoxide dismutase (FSD) signalling pathway in salt stress. The kinase activity of MPK6 was totally turned off in mkk5, whereas the activity of MPK3 was only partially blocked. MKK5 interacted with the MEKK1 protein that was also involved in the salt-induced FSD signalling pathway. These data suggest that salt-induced FSD2 and FSD3 expressions are influenced by MEKK1 via MKK5-MPK6 coupled signalling. This MAP kinase cascade (MEKK1, MKK5, and MPK6) mediates the salt-induced expression of iron superoxide dismutases. PMID- 26136266 TI - Asymmetric transcriptomic signatures between the cob and florets in the maize ear under optimal- and low-nitrogen conditions at silking, and functional characterization of amino acid transporters ZmAAP4 and ZmVAAT3. AB - Coordinated functioning of the cob and florets of the maize ear confers grain yield. The cob is critical for carbon partitioning and assimilated nitrogen (N) supply for grain development. However, molecular recognition of the cob and peripheral florets, characterization of genes mediating translocation of N assimilates, and responses of these two tissues to low N (LN) remain elusive. Transcriptional profiling of the ear of a maize hybrid at silking in the field revealed 1864 differentially expressed genes between the cob and florets, with 1314 genes up-regulated in the cob and 550 genes up-regulated in florets. The cob was characterized by striking enrichment of genes that are involved in carbon/N transport and metabolism, consistent with the physiological role of the cob in carbon/N storage and transfer during ear development. The florets were characterized by enrichment of hormone signalling components and development related genes. We next examined the response of the cob and florets to LN stress. LN caused differential expression of 588 genes in the cob and only 195 genes in the florets, indicating that the cob dominated the response of the ear to LN at the transcriptional level. LN caused comprehensive alterations such as carbon/N metabolism or partitioning, hormone signalling and protein phosphorylation in terms of gene expression in the cob and/or florets. Fourteen genes responsive specifically to LN provided potential molecular markers for N-efficient maize breeding. We further functionally characterized two newly identified broad spectrum amino acid transporters, ZmAAP4 and ZmVAAT3, that showed distinct expression patterns in the cob and florets and potentially important roles in amino-N mobilization in the ear. While both proteins could transport various amino acids into yeast or Arabidopsis cells, ZmAAP4 appeared to have higher efficiencies than ZmVAAT3 in transporting seven out of 22 examined amino acids. PMID- 26136267 TI - Brassinazole resistant 1 (BZR1)-dependent brassinosteroid signalling pathway leads to ectopic activation of quiescent cell division and suppresses columella stem cell differentiation. AB - Previous publications have shown that BRI1 EMS suppressor 1 (BES1), a positive regulator of the brassinosteroid (BR) signalling pathway, enhances cell divisions in the quiescent centre (QC) and stimulates columella stem cell differentiation. Here, it is demonstrated that BZR1, a BES1 homologue, also promotes cell divisions in the QC, but it suppresses columella stem cell differentiation, opposite to the action of BES1. In addition, BR and its BZR1-mediated signalling pathway are shown to alter the expression/subcellular distribution of pin-formed (PINs), which may result in changes in auxin movement. BR promotes intense nuclear accumulation of BZR1 in the root tip area, and the binding of BZR1 to the promoters of several root development-regulating genes, modulating their expression in the root stem cell niche area. These BZR1-mediated signalling cascades may account for both the ectopic activation of QC cell divisions as well as the suppression of the columella stem cell differentiation. They could also inhibit auxin-dependent distal stem cell differentiation by antagonizing the auxin/WOX5-dependent pathway. In conclusion, BZR1-/BES1-mediated BR signalling pathways show differential effects on the maintenance of root apical meristem activities: they stimulate ectopic QC division while they show opposite effects on the differentiation of distal columella stem cells in a BR concentration- and BZR1-/BES1-dependent manner. PMID- 26136268 TI - Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells. AB - Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca(2+) levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane-microtubule inter-relationship is discussed. PMID- 26136269 TI - Map-based cloning and characterization of BPH29, a B3 domain-containing recessive gene conferring brown planthopper resistance in rice. AB - Rice (Oryza sativa L.) production, essential for global food security, is threatened by the brown planthopper (BPH). The breeding of host-resistant crops is an economical and environmentally friendly strategy for pest control, but few resistance gene resources have thus far been cloned. An indica rice introgression line RBPH54, derived from wild rice Oryza rufipogon, has been identified with sustainable resistance to BPH, which is governed by recessive alleles at two loci. In this study, a map-based cloning approach was used to fine-map one resistance gene locus to a 24kb region on the short arm of chromosome 6. Through genetic analysis and transgenic experiments, BPH29, a resistance gene containing a B3 DNA-binding domain, was cloned. The tissue specificity of BPH29 is restricted to vascular tissue, the location of BPH attack. In response to BPH infestation, RBPH54 activates the salicylic acid signalling pathway and suppresses the jasmonic acid/ethylene-dependent pathway, similar to plant defence responses to biotrophic pathogens. The cloning and characterization of BPH29 provides insights into molecular mechanisms of plant-insect interactions and should facilitate the breeding of rice host-resistant varieties. PMID- 26136270 TI - Antagonistic peptide technology for functional dissection of CLE peptides revisited. AB - In the Arabidopsis thaliana genome, over 1000 putative genes encoding small, presumably secreted, signalling peptides can be recognized. However, a major obstacle in identifying the function of genes encoding small signalling peptides is the limited number of available loss-of-function mutants. To overcome this, a promising new tool, antagonistic peptide technology, was recently developed. Here, this antagonistic peptide technology was tested on selected CLE peptides and the related IDA peptide and its usefulness in the context of studies of peptide function discussed. Based on the analyses, it was concluded that the antagonistic peptide approach is not the ultimate means to overcome redundancy or lack of loss-of-function lines. However, information collected using antagonistic peptide approaches (in the broad sense) can be very useful, but these approaches do not work in all cases and require a deep insight on the interaction between the ligand and its receptor to be successful. This, as well as peptide ligand structure considerations, should be taken into account before ordering a wide range of synthetic peptide variants and/or generating transgenic plants. PMID- 26136272 TI - Productivity of authors in the field of diabetes: bibliographic analysis of trial publications. AB - OBJECTIVE: To determine whether trial publications of glucose lowering drugs are dominated by a small group of highly prolific authors ("supertrialists") and to identify some of their characteristics. DESIGN: Bibliographic analysis of trial publications. DATA SOURCES AND REVIEW METHODS: We searched PubMed for all randomised controlled trials (RCTs) relating to glucose lowering drugs published between 1 January 1993 and 31 December 2013. From these publications we identified the 110 most prolific authors using PubReMiner. The 991 RCTs they published were examined for various characteristics such as author number, commercial sponsorship, company authorship, conflicts of interest, etc. The track record of the top 11 authors was studied in more detail. MAIN OUTCOME MEASURE: Proportion of articles published by the top 110 and the top 11 authors. RESULTS: 3782 articles from 13,592 authors were identified. The top 110 authors were named in 1227 (32.4%) of all articles, and the top 11 authors in 397 (10.5%) of all articles. The top 110 authors published 991 RCTs for a median of 20 (range 4-77) RCTs per author; the top 11 published 354 RCTs for a median of 42 (36-77) RCTs per author. Of the 110 top authors, 48 were employed by a pharmaceutical company. Of the 991 RCTs, 906 were commercially sponsored. Of 704 articles that could be assessed for conflicts of interest, only 42 (6%) were considered fully independent. Medical writing assistance was acknowledged in 439 (44.3%) of 991 RCTs. CONCLUSION: The past two decades have seen an explosive increase in the number of published clinical trials regarding glucose lowering treatment. Some authors have made a disproportionate contribution to the therapeutic evidence base; one third of the RCT evidence base on glucose lowering drug treatment for diabetes was generated by <: 1% of authors. Of these, 44% were company employees and 56% were academics who work closely with the pharmaceutical companies. PMID- 26136273 TI - Glutamine Supplementation in Parenteral Nutrition and Intensive Care Unit Patients: Are We Throwing the Baby Out With the Bathwater? PMID- 26136271 TI - Strigolactones as an auxiliary hormonal defence mechanism against leafy gall syndrome in Arabidopsis thaliana. AB - Leafy gall syndrome is the consequence of modified plant development in response to a mixture of cytokinins secreted by the biotrophic actinomycete Rhodococcus fascians. The similarity of the induced symptoms with the phenotype of plant mutants defective in strigolactone biosynthesis and signalling prompted an evaluation of the involvement of strigolactones in this pathology. All tested strigolactone-related Arabidopsis thaliana mutants were hypersensitive to R. fascians. Moreover, treatment with the synthetic strigolactone mixture GR24 and with the carotenoid cleavage dioxygenase inhibitor D2 illustrated that strigolactones acted as antagonistic compounds that restricted the morphogenic activity of R. fascians. Transcript profiling of the MORE AXILLARY GROWTH1 (MAX1), MAX2, MAX3, MAX4, and BRANCHED1 (BRC1) genes in the wild-type Columbia-0 accession and in different mutant backgrounds revealed that upregulation of strigolactone biosynthesis genes was triggered indirectly by the bacterial cytokinins via host-derived auxin and led to the activation of BRC1 expression, inhibiting the outgrowth of the newly developing shoots, a typical hallmark of leafy gall syndrome. Taken together, these data support the emerging insight that balances are critical for optimal leafy gall development: the long-lasting biotrophic interaction is possible only because the host activates a set of countermeasures-including the strigolactone response-in reaction to bacterial cytokinins to constrain the activity of R. fascians. PMID- 26136274 TI - An environmentally friendly method for the determination of pentachlorophenol in paper packaging materials using ultrasonic-assisted micellar extraction. AB - Ultrasonic-assisted micellar extraction coupled with high-pressure liquid chromatography has been developed for the determination of pentachlorophenol (PCP) in paper packaging materials. A non-ionic surfactant, polyethylene glycol sorbitan monolaurate (Tween 20), was used for ultrasonic extraction and the method was applied to different paper packaging materials under optimized conditions. The recoveries for spiked samples were 83-90.1% and relative standard deviations were <5.0%. The limit of detection and the limit of quantification for PCP were 0.9 and 2.0 ug/g, respectively. Results confirmed that this relatively simple procedure proved satisfactory for the determination of PCP in paper packaging materials. PMID- 26136275 TI - Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: Safe and Apparently Efficacious But Does Reporting of Aggregate Outcomes Hide Less Favorable Results, Experienced by a Substantial Proportion of Patients? AB - AIMS: To describe individual and aggregate outcomes for patients undergoing alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Retrospective case series reviewing all patients undergoing ASA at a United Kingdom tertiary referral center from 2000-2012. Aggregate and individual outcomes are described in terms of symptomatic and hemodynamic response. RESULTS: Eighty-eight patients were reviewed. Alcohol was delivered in 84, with clinical status data available in 82 and hemodynamic data available in 74. All patients had resting or exercise stress left ventricular outflow tract (LVOT) gradient >50 mm Hg. Mean age was 60.3 +/- 14.3 years. Follow-up period was 4.2 +/- 3.3 years. Twenty-four patients (27%) required >=2 procedures. Complete heart block was observed in 17%. New York Heart Association (NYHA) class pre ASA was 2.80 +/- 0.46, improving to 1.92 +/- 0.84 post ASA (P<.001). Fifty-eight out of 82 patients (71%) had improved NYHA class. Resting peak gradient was 99.80 +/- 45.86 mm Hg. Post-ASA peak gradient fell to 23.77 +/- 41.87 mm Hg (P<.001). Sixty-one out of 74 patients (82%) had successful treatment of LVOT gradient. A successful outcome in both symptomatic and gradient treatment was seen in 66% of patients. No patient who received alcohol suffered sudden cardiac death. Fifteen patients had implantable cardioverter defibrillator implantation; no appropriate therapy was delivered. CONCLUSIONS: ASA is safe, with few major complications. Aggregate outcomes are good, but can hide individual failure. There is a need to refine case selection, procedure planning, and performance to secure more uniform favorable outcomes. PMID- 26136276 TI - Alcohol Septal Ablation: What Have We Learned From Multicenter Versus Single Center Experiences, and Aggregate Versus Individualized Outcomes? PMID- 26136277 TI - Impact of a Disposable Sterile Radiation Shield on Operator Radiation Exposure During Percutaneous Coronary Intervention of Chronic Total Occlusions. AB - BACKGROUND: Daily radiation exposure over many years can adversely impact the health of medical professionals. METHODS: Operator radiation exposure was recorded for 124 percutaneous coronary interventions (PCIs) performed at our institution between August 2011 and May 2013: 69 were chronic total occlusion (CTO)-PCIs and 55 were non-CTO PCIs. A disposable radiation protection sterile drape (Radpad; Worldwide Innovations & Technologies, Inc) was used in all CTO-PCI cases vs none of the non-CTO PCI cases. Operator radiation exposure was compared between CTO and non-CTO PCIs. RESULTS: Mean age was 64.6 +/- 6.2 years and 99.2% of the patients were men. Compared with non-CTO PCI, patients undergoing CTO-PCI were more likely to have congestive heart failure, to be current smokers, and to have longer lesions, and less likely to have prior PCI and a saphenous vein graft target lesion. CTO-PCI cases had longer procedural time (median: 123 minutes [IQR, 85-192 minutes] vs 27 minutes [IQR, 20-44 minutes]; P<.001), fluoroscopy time (35 minutes [IQR, 19-54 minutes] vs 8 minutes [IQR, 5-16 minutes]; P<.001), number of stents placed (2.4 +/- 1.5 vs 1.7 +/- 0.9; P<.001), and patient air kerma radiation exposure (3.92 Gray [IQR, 2.48-5.86 Gray] vs 1.22 Gray [IQR, 0.74 1.90 Gray]; P<.001), as well as dose area product (267 Gray*cm2 [IQR, 163-4.25 Gray*cm2] vs 84 Gray*cm2 [IQR, 48-138 Gray*cm2]; P<.001). In spite of higher patient radiation exposure, operator radiation exposure was similar between the two groups (20 MUSv [IQR, 9.5-31 MUSv] vs 15 MUSv [IQR, 7-23 MUSv]; P=.07). CONCLUSIONS: Operator radiation exposure during CTO-PCI can be reduced to levels similar to less complicated cases with the use of a disposable sterile radiation protection shield. PMID- 26136278 TI - Physician, Shield Thyself! PMID- 26136280 TI - Let "US" Guide the Way? PMID- 26136279 TI - Ultrasound-Guided Catheterization of the Femoral Artery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - OBJECTIVES: The goal of this meta-analysis was to determine the utility of real time two-dimensional (2D) ultrasound guidance for femoral artery catheterization. BACKGROUND: Despite the shift toward establishing vascular access via the radial artery rather than the femoral artery, femoral artery cannulation is still frequent in cardiac catheterization. Since vascular complications related to femoral artery cannulation can be quite devastating, preventing these complications is vital. METHODS: A comprehensive literature search of Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials was performed. Additionally, five years of conference abstracts from critical care, interventional radiology, vascular surgery, and cardiology were reviewed. Two independent reviewers identified prospective, randomized controlled trials comparing ultrasound guidance with traditional palpation techniques of femoral artery catheterization (with or without fluoroscopy). Data were extracted on study design, study size, operator and patient characteristics, complication rates, first-pass success, procedure time, and number of attempts. RESULTS: Four trials with a total of 1422 subjects were included in the review, with 703 subjects in the palpation group and 719 subjects in the ultrasound-guided group. Compared with traditional methods, ultrasound guidance for femoral artery catheterization was associated with 49% reduction in overall complications, including hematoma and accidental venipuncture (relative risk, 0.51; 95% confidence interval, 0.28-0.91). It was also associated with 42% improvement in the likelihood of first-attempt success (relative risk, 1.42; 95% confidence interval, 1.01-2.00). CONCLUSIONS: The use of real-time 2D ultrasound guidance for femoral artery catheterization decreases life-threatening vascular complications and improves first-pass success rate. PMID- 26136281 TI - Feasibility and Safety of Routine Transpedal Arterial Access for Treatment of Peripheral Artery Disease. AB - OBJECTIVE: To demonstrate the feasibility and safety of transpedal arterial access for lower-extremity angiography and intervention. BACKGROUND: Traditionally, the femoral artery is chosen for the initial access site in symptomatic peripheral artery disease (PAD), but this approach carries a substantial portion of the entire procedural complication risk. METHODS: 80 patients were prospectively evaluated for the treatment of PAD between May and July 2014. All patients underwent peripheral angiography, and intervention if necessary. A pedal artery was the initial access site for all patients. Under ultrasound guidance, one of the pedal arteries was visualized and accessed, and a 4 Fr Glidesheath was inserted. Retrograde orbital atherectomy and balloon angioplasty were performed with a 4 Fr sheath or upsizing to a 6 Fr Glidesheath Slender (Terumo) for stenting as needed. Clinical and ultrasound assessment of the pedal arteries were performed before the procedure and at 1-month follow-up. RESULTS: Diagnostic transpedal peripheral angiography was performed in all 80 patients. 43 out of 51 patients (84%) who required intervention were successful using a pedal artery as the sole access site. No immediate or delayed access-site complications were detected. Clinical follow-up was achieved in 77 patients (96%) and access artery patency was demonstrated by ultrasound at 1 month in 100% of patients. CONCLUSION: The routine use of a transpedal approach for the treatment of PAD may be feasible and safe. Pedal artery access may also avoid many of the complications associated with the traditional femoral approach, but further study is needed. PMID- 26136282 TI - Ultrasound-Guided Tibial Pedal Arterial Access: Growing Alternative Strategy in the Treatment Of Complex Peripheral Artery Disease. PMID- 26136283 TI - Predictors of Permanent Pacemaker Insertion Following Transcatheter Aortic Valve Replacement With the CoreValve Revalving System Based on Computed Tomography Analysis: An Asian Multicenter Registry Study. AB - BACKGROUND: To determine predictive variables for permanent pacemaker (PPM) insertion after transcatheter aortic valve replacement (TAVR) with the CoreValve Revalving System (CRS). METHODS AND RESULTS: A total of 121 patients with severe aortic stenosis (AS) were recruited from six Asian medical centers between March 2010 and May 2013. Four patients with preexisting PPM were excluded. The mean age of the remaining 117 patients was 81.2 +/- 5.1 years. Twenty-three patients (19.7%) required post-TAVR PPM, with a median time-to-insertion of 7 days (interquartile range, 5-13 days). Two variables were identified as independent predictors of PPM: (1) device depth from the non-coronary cusp (NCC) (odds ratio [OR], 1.263; P=.02) determined by aortic root angiography; and (2) the perimeter stretching index (OR, 1.584; P<.001) determined by computed tomography. The predictive cut-off values were as follows: a perimeter stretching index >1.13 (P<.001) and a device depth from the NCC >7.8 mm (P<.001). The diagnostic accuracy of these variables was 93.2% and 71%, respectively. CONCLUSION: Depth of the device from the NCC and the perimeter stretching index are independent predictors of PPM insertion after CRS-TAVR. PMID- 26136284 TI - An Initiative Technique to Facilitate Axillary Vein Puncture During CRT Implantation. AB - OBJECTIVES: The aim of the study was to describe a new technique to minimize requirement of contrast and the time to puncture the axillary vein during implantation of cardiac resynchronization therapy (CRT) devices. BACKGROUND: One of the challenges to the wide applications of CRT has been the technical difficulty encountered while obtaining venous access utilizing axillary venous puncture. This is mainly due to vague anatomical land marks. The axillary vein is the preferred access point because of fewer associated risks and better lead protection in the future. METHODS: We introduced a 0.035 mm guidewire retrogradely from the femoral vein up to the left axillary vein. A single anteroposterior scene at 7.5 frames/second was captured while the guidewire was in the vein. The scene was kept as a roadmap for the axillary vein puncture during the implantation procedure. RESULTS: The axillary vein was accessed in all patients (100%) and the time to axillary vein puncture was <1 minute in 36 patients (41%) and between 1-5 minutes in the remaining patients. There were no related vascular complications and no contrast venography was required. CONCLUSION: The use of retrograde axillary vein wiring simplifies axillary venous puncture and minimizes the need for contrast media during CRT device implantation without compromising visualized anatomy. PMID- 26136285 TI - Can Adding Laboratory Values Improve Risk-Adjustment Mortality Models Using Clinical Percutaneous Cardiac Intervention Registry Data? AB - BACKGROUND: Registry data for percutaneous coronary intervention (PCI) are being used in New York and Massachusetts and by the American College of Cardiology to risk-adjust provider mortality rates. These registries contain very few numerical laboratory data for risk adjustment. METHODS: For 20 hospitals, New York's PCI registry data from 2008-2010 were used to develop statistic models for predicting in-hospital/30-day mortality with and without appended laboratory data. Discrimination, calibration, correlation in hospital's risk-adjusted mortality rates, and differences in hospital quality outlier status were compared for the two models. RESULTS: The discrimination of the risk-adjustment models was very similar (C-statistic = 0.898 from the registry model vs C-statistic = 0.908 from the registry/laboratory model; P=.40). Most of the non-laboratory variables in the two models were identical, except that the registry model contained malignant ventricular arrhythmia and the registry/laboratory model contained previous coronary artery bypass surgery. The registry/laboratory model also contained albumin <=3.3 g/dL, creatine kinase >=600 U/L, glucose >=270 mg/dL, platelet count >350 k/MUL, potassium >51 mmol/L, and partial thromboplastin time >40 seconds. The addition of laboratory data did not affect outlier status for better performing hospitals, but there were differences in identifying the hospitals with significantly higher risk-adjusted mortality rates. CONCLUSIONS: Adding laboratory data did not significantly improve the risk-adjustment mortality models' performance and did not dramatically change the quality assessment of hospitals. The pros and cons of adding key laboratory variables to PCI registries require further evaluation. PMID- 26136286 TI - Trends and Outcomes of Radial Approach in Left-Main Bifurcation Percutaneous Coronary Intervention in the Drug-Eluting Stent Era: A Two-Center Registry. AB - OBJECTIVE: To analyze the immediate and long-term outcomes of transradial (TR) percutaneous coronary intervention (PCI) to unprotected left main stem (ULMS) bifurcation and to assess the main aspects affecting access-site choice in this specific PCI setting. BACKGROUND: TR-PCI to the ULMS is feasible, but data specifically comparing TR and transfemoral (TF) approaches in ULMS-bifurcation PCI are limited. METHODS: We set up a two-center (Rome, Italy and Oxford, United Kingdom) retrospective registry aimed at comparing the immediate and 1-year outcomes of consecutive patients who underwent ULMS-bifurcation PCI with drug eluting stent implantation from 2005 to 2013 using the TF or TR approach. Clinical endpoints were: total mortality; major adverse cardiac and cerebrovascular event (MACCE) rate; and net adverse clinical event (NACE) rate. RESULTS: A total of 467 patients undergoing ULMS-bifurcation PCI were enrolled (221 TF and 244 TR). TR approach was increasingly adopted over time for both simple and complex procedures. No significant differences were observed between the TR and TF groups in terms of 1-year mortality (10.7% vs 9.8%; P=.79) and MACCE (18.2% vs 15.2%; P=.44). TR patients, as compared with TF, had significantly fewer access-site complications (2.0% vs 6.3% in TF; P=.02), resulting in a significant reduction of NACE rate (6.9% vs 15.7;%; P=.01). CONCLUSION: In patients undergoing ULMS-bifurcation PCI, the selection of TR instead of TF approach is associated with similar early and long-term ischemic complications and with a significant reduction of access-site complications, resulting in lower NACE rate. PMID- 26136287 TI - Board Games. PMID- 26136288 TI - Patient-Specific Three-Dimensional Aortocoronary Model for Percutaneous Coronary Intervention of a Totally Occluded Anomalous Right Coronary Artery. AB - Percutaneous coronary intervention (PCI) for anomalous coronary arteries is often difficult because the support provided by the guide catheter is insufficient. We encountered a patient with severe three-vessel coronary disease including a totally occluded anomalous right coronary artery (RCA) originating from the left sinus of Valsalva. Initial PCI for the anomalous RCA via the transradial approach failed. Therefore, we constructed a three-dimensional (3D) aortocoronary model and conducted an in vitro simulation to plan the second PCI and found that a Judkins left (JL) 3.5 guide catheter in the power position yielded maximum backup support for the anomalous RCA. Thus, the second PCI was conducted using an 8 Fr JL 3.5 guide catheter in the power position via the transfemoral approach. The procedure was smooth and successful, without any adverse events. Our experience suggests that case-specific 3D models are useful for strategic planning of complex PCIs. PMID- 26136289 TI - Rotational Atherectomy Combined With Bioresorbable Vascular Scaffold Implantation: A Feasible Approach for Recurrent In-stent Restenosis When Other Therapies Failed. AB - The optimal treatment for recurrent in-stent restenosis (ISR) is uncertain. Everolimus-eluting bioresorbable vascular scaffold (BVS) use has been reported in a few cases as an interesting alternative, as it avoids long-term metal exposure to coronary circulation. Nevertheless, the underlying neointima and the multiple layers of previously implanted stents with underexpanded struts may contribute to recurrent ISR following BVS placement. We describe a feasible combined treatment for recurrent ISR in 2 patients using neointimal debulking and ablation of underexpanded stents by rotational atherectomy followed by BVS implantation. This conceptually attractive approach has not yet been reported. PMID- 26136290 TI - Reentry-Catheter Assisted SAFARI Technique. AB - Reentry catheters have become an important tool in the treatment of chronic total occlusion of the peripheral vasculature. Their use has been demonstrated in the treatment of aortoiliac disease as well as femoropopliteal disease. Success rates may vary depending on operator experience and lesion characteristics, but in general are reported to be around 85% in facilitating reentry. In the event of reentry failure, alternative strategies may be required to achieve procedural success. We describe an alternative strategy to achieve success with the use of Outback and Pioneer reentry catheters when initial reentry fails. PMID- 26136291 TI - Direct Observation of the Reversible Two-State Unfolding and Refolding of an alpha/beta Protein by Single-Molecule Atomic Force Microscopy. AB - Directly observing protein folding in real time using atomic force microscopy (AFM) is challenging. Here the use of AFM to directly monitor the folding of an alpha/beta protein, NuG2, by using low-drift AFM cantilevers is demonstrated. At slow pulling speeds (<50 nm s(-1)), the refolding of NuG2 can be clearly observed. Lowering the pulling speed reduces the difference between the unfolding and refolding forces, bringing the non-equilibrium unfolding-refolding reactions towards equilibrium. At very low pulling speeds (ca. 2 nm s(-1)), unfolding and refolding were observed to occur in near equilibrium. Based on the Crooks fluctuation theorem, we then measured the equilibrium free energy change between folded and unfolded states of NuG2. The improved long-term stability of AFM achieved using gold-free cantilevers allows folding-unfolding reactions of alpha/beta proteins to be directly monitored near equilibrium, opening the avenue towards probing the folding reactions of other mechanically important alpha/beta and all-beta elastomeric proteins. PMID- 26136292 TI - Phase Transformations of Cobalt Oxides in CoxOy-ZnO Multipod Nanostructures via Combustion from Thermopower Waves. AB - The study of combustion at the interfaces of materials and chemical fuels has led to developments in diverse fields such as materials chemistry and energy conversion. Recently, it has been suggested that thermopower waves can utilize chemical-thermal-electrical-energy conversion in hybrid structures comprising nanomaterials and combustible fuels to produce enhanced combustion waves with concomitant voltage generation. In this study, this is the first time that the direct phase transformation of Co-doped ZnO via instant combustion waves and its applications to thermopower waves is presented. It is demonstrated that the chemical combustion waves at the surfaces of Co3O4-ZnO multipod nanostructures (deep brown in color) enable direct phase transformations to newly formed CoO ZnO(1-x) nanoparticles (olive green in color). The oxygen molecules are released from Co3O4-ZnO to CoO-ZnO(1-x) under high-temperature conditions in the reaction front regime in combustion, whereas the CoO-ZnO multipod nanoparticles do not undergo any transformations and thus do not experience any color change. This oxygen-release mechanism is applicable to thermopower waves, enhances the self propagating combustion velocity, and forms lattice defects that interrupt the charge-carrier movements inside the nanostructures. The chemical transformation and corresponding energy transport observed in this study can contribute to diverse potential applications, including direct-combustion synthesis and energy conversion. PMID- 26136293 TI - 1,3-Butadienyl Dianions as Non-Innocent Ligands: Synthesis and Characterization of Aromatic Dilithio Rhodacycles. AB - Herein we report that 1,4-dilithio-1,3-butadienes, a type of 1,3-butadienyl dianion, can act as non-innocent ligands, taking electrons from low-valent transition metals. Dilithio reagents reacted with [{RhCl(cod)}2] to give dilithio rhodacycle 3 a. Single-crystal X-ray structural analysis revealed the structure of 3 a with averaged bond lengths. XPS data suggested that the oxidation state of Rh in 3 a was more likely to be Rh(3+). CDA/ECDA confirmed the electron-transfer process. (7)Li NMR spectra of 3 a and theoretical calculations revealed a considerable aromatic character. In this process, the dilithio compounds behaved as non-innocent ligands and formal oxidants. These results demonstrated that organolithium compounds with suitable pi-conjugation could be used as electron acceptor. PMID- 26136294 TI - AMP/GMP Analogs as Affinity ESIPT Probes for Highly Selective Sensing of Alkaline Phosphatase Activity in Living Systems. AB - Current probes for alkaline phosphatase (ALP) detection had been developed mainly by adding a phosphate group to a dye, which would lead to indistinct performance when implemented in a living system as several phosphatases exist together. In this study, the nucleotides adenosine monophosphate (AMP) and guanosine monophosphate (GMP) were introduced into 2'-(2'-hydroxyphenyl)-benzothiazole based probes, and highly fluorescent turn-on probes with good selectivity towards ALP over several phosphatases, as well as high affinity and low toxicity were obtained. In the presence of L-phenylalanine, an ALP inhibitor, a strong decrease in fluorescence recovery was observed. These probes allowed for real-time imaging of endogenous ALP activity in living cells as well as in a zebrafish model. PMID- 26136295 TI - Shape-Controlled Synthesis and Self-Sorting of Covalent Organic Cage Compounds. AB - The directional bonding approach is a powerful tool to rationally control both shape and stoichiometry of three-dimensional objects built from rigid building blocks under dynamic covalent conditions. Co-condensation of catechol functionalized tribenzotriquinacene derivatives which have 90 degrees angles between the reactive sites and diboronic acids with bite angles of 60 degrees , 120 degrees , and 180 degrees , led to the efficient formation of, respectively, bipyramidal, tetrahedral, or cubic covalent organic cage compounds in a predictable manner. Investigations on the self-sorting of ternary mixtures containing two competitive boronic acids revealed either narcissistic or social self-sorting depending on the stability of the segregated cages relative to feasible three-component assemblies. PMID- 26136296 TI - Chiral Metallo-Supramolecular Complex Directed Enantioselective Self-Assembly of beta-Sheet Breaker Peptide for Amyloid Inhibition. AB - Chiral recognition plays an important role for biomacromolecules involved self assembly and further affects their biological functions. Herein, it is demonstrated that two chiral metal complexes can enantioselectively bind with Abeta15-20, leading to the formation of different self-assembled nanostructures. With the ability of both metal complexes and Abeta15-20 to inhibit Abeta1-40 aggregation, the NiM@P hybrid particles can act as bifunctional Abeta inhibitors. PMID- 26136297 TI - Asymmetric Introgression in a Spotted Salamander Hybrid Zone. AB - Before the establishment of reproductive isolation, deeply diverged intraspecific lineages can experience complex genetic and behavioral interactions as they come into secondary contact. Divergent selective and demographic processes mediate gene flow among lineages, resulting in hybrid zones with complex biogeographic structure. Discordance in the biogeographic patterns of autosomal and maternally inherited loci provides a useful window to infer the processes mediating admixture and introgression across hybrid zones. Here, we sampled 489 genotypes across a hybrid zone between 2 phylogeographic lineages of the spotted salamander, Ambystoma maculatum, and characterize discordant patterns of nuclear and mitochondrial introgression across the contact boundary. Our results indicate asymmetric introgression of nuclear DNA beyond the contact boundary from the western to eastern lineage, with introgression of eastern mitochondrial DNA into the western lineage. We discuss alternative mechanisms for this pattern and attribute this result to neutral patterns of population expansion of the western lineage into the east in combination with female mate choice for larger-bodied western males. Our results underscore the complexity of interacting mechanisms that give rise to reproductive asymmetries in the earliest stages of the speciation process. PMID- 26136298 TI - P wave detection and delineation in the ECG based on the phase free stationary wavelet transform and using intracardiac atrial electrograms as reference. AB - Robust and exact automatic P wave detection and delineation in the electrocardiogram (ECG) is still an interesting but challenging research topic. The early prognosis of cardiac afflictions such as atrial fibrillation and the response of a patient to a given treatment is believed to improve if the P wave is carefully analyzed during sinus rhythm. Manual annotation of the signals is a tedious and subjective task. Its correctness depends on the experience of the annotator, quality of the signal, and ECG lead. In this work, we present a wavelet-based algorithm to detect and delineate P waves in individual ECG leads. We evaluated a large group of commonly used wavelets and frequency bands (wavelet levels) and introduced a special phase free wavelet transformation. The local extrema of the transformed signals are directly related to the delineating points of the P wave. First, the algorithm was studied using synthetic signals. Then, the optimal parameter configuration was found using intracardiac electrograms and surface ECGs measured simultaneously. The reverse biorthogonal wavelet 3.3 was found to be optimal for this application. In the end, the method was validated using the QT database from PhysioNet. We showed that the algorithm works more accurately and more robustly than other methods presented in literature. The validation study delivered an average delineation error of the P wave onset of 0.32+/-12.41 ms when compared to manual annotations. In conclusion, the algorithm is suitable for handling varying P wave shapes and low signal-to-noise ratios. PMID- 26136299 TI - Anti-angiogenic and antiproliferative properties of the lichen substances (-) usnic acid and vulpinic acid. AB - The anti-proliferative activities of the lichen substances (-)-usnic acid and vulpinic acid on the viability of HepG2 hepatocarcinoma cells, NS20Y neuroblastoma cells and HUVEC endothelial cells were studied by the MTT assay. The anti-angiogenic potential of the substances was determined by the endothelial tube formation assay. Both lichen substances exhibited strong anti-angiogenic activity and were more cytotoxic to the cancer cell lines than to the normal cell line, but vulpinic acid has more potential as an anti-angiogenic substance because of its low cytotoxicity and stronger anti-angiogenic activity on the HUVEC cell line. PMID- 26136300 TI - Performance of strip-based glucose meters and cassette-based blood gas analyzer for monitoring glucose levels in a surgical intensive care setting. AB - BACKGROUND: We verified the analytical performance of strip-based handheld glucose meters (GM) for prescription use, in a comparative split-sample protocol using blood gas samples from a surgical intensive care unit (ICU). METHODS: Freestyle Precision Pro (Abbott), StatStrip Connectivity Meter (Nova), ACCU-CHEK Inform II (Roche) were evaluated for recovery/linearity, imprecision/repeatability. The GMs and the ABL90 (Radiometer) blood gas analyzer (BGA) were tested for relative accuracy vs. the comparator hexokinase glucose-6 phosphate-dehydrogenase (HK/G6PDH) assay on a Cobas c702 analyzer (Roche). RESULTS: Recovery of spiked glucose was linear up to 19.3 mmol/L (347 mg/dL) with a slope of 0.91-0.94 for all GMs. Repeatability estimated by pooling duplicate measurements on samples below (n=9), in (n=51) or above (n=80) the 4.2-5.9 mM (74 106 mg/dL) range were for Freestyle Precision Pro: 4.2%, 4.0%, 3.6%; StatStrip Connectivity Meter: 4.0%, 4.3%, 4.5%; and ACCU-CHEK Inform II: 1.4%, 2.5%, 3.5%. GMs were in agreement with the comparator method. The BGA outperformed the GMs, with a MARD of 3.9% compared to 6.5%, 5.8% and 4.4% for the FreeStyle, StatStrip and ACCU-CHEK, respectively. Zero % of the BGA results deviated more than the FDA 10% criterion as compared to 9.4%, 3.7% and 2.2% for the FreeStyle, StatStrip and ACCU-CHEK, respectively. For all GMs, icodextrin did not interfere. Variation in the putative influence factors hematocrit and O2 tension could not explain observed differences with the comparator method. CONCLUSIONS: GMs quantified blood glucose in whole blood at about the 10% total error criterion, proposed by the FDA for prescription use. PMID- 26136301 TI - Hemoglobin A1c reported in units and diagnostic cut-offs in relation to the international recommendations. PMID- 26136302 TI - Cardiac troponin I release after a basketball match in elite, amateur and junior players. AB - BACKGROUND: Available scientific data related to cardiac troponin I (cTnI) release after intermittent exercise is limited. It is also of interest to determine what personal or environmental factors mediate the exercise-induced release of cTnI. This study had two objectives: 1) to examine the individual release of cTnI to a basketball match; and 2) to establish the influence of athlete status as well as biological age on cTnI release. METHODS: Thirty-six basketball players (12 adult elite [PBA]: 27.3+/-4.1 years, 12 adult amateur [ABA]: 29.6+/-2.9 years, and 12 junior elite [JBA]: 16.6+/-0.9 years) participated in a simulated basketball match with serial assessment of cTnI at rest, immediately post- and at 1, 3, 6, 12, and 24 h post-exercise. RESULTS: The basketball match increased cTnI levels (pre: median [range]; 0.006 [0.001-0.026]; peak post: 0.024 [0.004-0.244] MUg/L; p=0.000), with substantial individual variability in peak values. PBA and JBA players showed higher baseline and post exercise cTnI values than ABA (all p<0.05). Peak cTnI exceeded the upper reference limit (URL) in the 26% of players (3 PBA; 6 JBA). CONCLUSIONS: The current results suggest that intermittent exercise can promote the appearance of cTnI and that this is potentially mediated by athlete status. PMID- 26136303 TI - Liquid citrate acidification introduces significant glucose bias and leads to misclassification of patients with diabetes. AB - BACKGROUND: Glucose measurements are crucial in diabetes diagnosis. We aimed to assess the effectiveness of liquid citrate acidification in preventing glycolysis and investigate glucose stability in serum, sodium fluoride (NaF/KOx) and Glucomedics tubes. METHODS: Samples from 40 participants were collected in serum, lithium-heparin (LiH), sodium fluoride/potassium oxalate (NaF/KOx) and Glucomedics tubes. Glucose was measured within 60 min (baseline), 120 and 180 min from venipuncture. Serum, NaF/KOx and Glucomedics values at baseline were compared to LiH glucose concentration. Additionally, glucose values measured at 120 and 180 min from each tube were compared with the baseline value. Mean absolute bias for each tube and time point was calculated and compared to recommended criteria. The regression equation obtained comparing citrate to NaF/KOx tubes was used to recalculate glucose results retrieved from the laboratory information system. RESULTS: Glucose measured in Glucomedics was higher (9.9%; p<0.001), while glucose in NaF/KOx and serum was lower compared to LiH (2.4%; p<0.001 and 3.2%; p<0.001, respectively). Biases for all tubes were clinically significant. Glucose remained unchanged at room temperature in all tubes for up to 180 min after venipuncture. Observed bias caused by Glucomedics leads to a 10.6% increase in diabetes prevalence (p<0.001). CONCLUSIONS: Inhibition of glycolysis is most effectively achieved using liquid citrate acidification, compared to LiH, NaF/KOx or serum. Due to clinically significant bias relative to reference glucose, the interchangeable use of different tube types for serial glucose measurements is not recommended. The replacement of NaF/KOx with Glucomedics tubes substantially impacts glucose results, giving marked rise in diabetes prevalence. PMID- 26136305 TI - Dendrimers for theranostic applications. AB - Recently, there have been tremendous advances in the development of various nanotechnology-based platforms for diagnosis and therapy. These nanoplatforms, which include liposomes, micelles, polymers, and dendrimers, comprise highly integrated nanoparticles that provide multiple functions, such as targeting, imaging, and therapy. This review focuses on dendrimer-based nanocarriers that have recently been developed for 'theranostics (or theragnosis)', a combination of therapy and diagnostics. We discuss the in vitro and in vivo applications of these nanocarriers in strategies against diseases including cancer. We also explore the use of dendrimers as imaging agents for fluorescence imaging, magnetic resonance imaging, X-ray computed tomography, and nuclear medical imaging. PMID- 26136306 TI - Erratum to: Epigenetic considerations of the APOE gene. PMID- 26136304 TI - Is retinol binding protein 4 a link between adiposity and cancer? AB - Retinol binding protein 4 (RBP4) is synthesized in the liver where it binds vitamin A, retinol, and transports it to tissues throughout the body. It has been shown in some studies that the level of circulating RBP4 increases with body mass, and the protein has been implicated as a mediator in the development of insulin resistance and the metabolic disease. Adipose tissue serves as another site of RBP4 synthesis, accounting for its designation as an adipokine. In addition to its function as a transport protein, RBP4 serves as a signaling molecule which, by binding to the membrane receptor STRA6, triggers downstream activation of pro-oncogenic pathways including JAK2/STAT3/5. Taken together, available information suggests the possibility that RBP4 may be a link between obesity and cancer. PMID- 26136307 TI - US court upholds use of sedative in executions. PMID- 26136308 TI - Cationic Iridium/S-Me-BIPAM-Catalyzed Direct Asymmetric Intermolecular Hydroarylation of Bicycloalkenes. AB - Highly enantioselective cationic iridium-catalyzed hydroarylation of bicycloalkenes, by carbonyl-directed C-H bond cleavage, was accomplished using a newly synthesized sulfur-linked bis(phosphoramidite) ligand (S-Me-BIPAM). The reaction provides alkylated acetophenone or benzamide derivatives in moderate to excellent yields and good to excellent enantioselectivities. Notably, the hydroarylation reaction of 2-norbornene with N,N-dialkylbenzamide proceeds with excellent enantioselectivity (up to 99% ee) and high selectivity for the mono ortho-alkylation product. PMID- 26136309 TI - A Qualitative Analysis of Pediatric Patient Attitudes Regarding Family-Centered Rounds. AB - BACKGROUND AND OBJECTIVES: The American Academy of Pediatrics recommends family centered rounds (FCR) as standard practice for the inpatient setting. To date, there is limited research investigating the attitudes of pediatric patients regarding this shift in practice. The goal of this study was to explore pediatric patients' perspectives of their experiences during FCR. METHODS: We conducted a qualitative descriptive study based on results from 22 semi-structured interviews of school-aged and adolescent inpatients from September 2012 through October 2013. English-speaking patients, aged 7 to 18 years, who participated in FCR were eligible for inclusion. Transcripts were initially analyzed by using a constant comparative method. After completion of this initial analysis, a third reviewer independently reviewed all transcripts to verify the accuracy of the final coding scheme. RESULTS: The final coding scheme consisted of 5 main themes: team size, medical team interactions, content discussed on FCR, setting expectations, and timing and location of FCR. In general, patients expressed a wide array of positive, negative, and neutral impressions within each theme relating to their experiences with FCR. CONCLUSIONS: Patient comments regarding their experience with FCR offer unique perspectives from previously studied participants, including physicians, nurses, students, and parents. Future research aimed at evaluating the bedside rounding process should incorporate patients' views to realize the complete FCR experience. PMID- 26136310 TI - Pain Prevalence and Treatment Patterns in a US Children's Hospital. AB - OBJECTIVE: Hospitalized children experience significant pain despite improvement efforts. This study was undertaken to better understand the epidemiology of acute pain in hospitalized children and the extent to which existing measures reveal targets for improving pain management. METHODS: A cross-sectional survey was used to audit pain assessment, intensity, prevalence, source, and treatment hospital wide on a single day in 2011. Chart audits were performed on patients aged 0 to 21 years. All patients had the option to participate in a structured interview about their pain experience. RESULTS: The audit included 112 children, 47 of whom were interviewed. Pain prevalence obtained by child/parent interview (72%) was more than twice that documented by nurses (30%). Infants, but not cognitively impaired children, had significantly lower rates of pain detection and analgesic ordering than older age groups. Procedural pain was the most frequently cited source of pain among interviewed patients and was poorly addressed in the medical record. Fifty percent of children with documented moderate-to-severe pain received scheduled pain medications. More than one-third of interviewed patients would have wanted more pain medication if it could have been safely given. CONCLUSIONS: Specific gaps remain in the quality of pain management provided to hospitalized children. Focus on infant pain detection, assessment and management of procedural pain, and scheduled analgesic ordering are sensible targets for future process improvement efforts. PMID- 26136311 TI - Assessing the Relationship Between BMI and Resource Utilization in a Pediatric Trauma Population. PMID- 26136312 TI - Improving Clinician Attitudes of Respect and Trust for Persons With Sickle Cell Disease. AB - OBJECTIVE: To test the effect of 1 high-intensity, and 1 reduced-intensity, educational intervention designed to improve health care provider attitudes toward youth with sickle cell disease (SCD). METHODS: We exposed a regional sample of pediatric health care providers to a 2.5-day high-intensity educational and experiential intervention using videos about the SCD patient experience. Additionally, we traveled to a different set of regional health care institutions and offered pediatric providers a reduced-intensity intervention, consisting of a 90-minute lunchtime in-service centered on our same set of videos about the patient's experience. We assessed the impact of both interventions by taking pre/post measurements of the negative and positive attitudes expressed by participating providers toward patients with SCD. RESULTS: Both interventions tested elicited improvements in the SCD attitudes expressed by the pediatric providers as suggested through a reduction in measured negative attitude scores (20.0 vs 12.1, P < .001), and an improvement in positive attitude scores (67.1 vs 72.2, P < .001). Further testing suggested that the high-intensity intervention elicited a stronger effect than the reduced-intensity intervention across multiple attitudinal domains. CONCLUSIONS: Video-based interventions can be used to improve the attitudes of pediatric providers toward patients with SCD. The availability of interventions of varying intensities provides greater flexibility in designing efforts to advance the quality of SCD care through the improvement of provider attitudes. PMID- 26136314 TI - The Scope and Trends of Pediatric Hospitalizations in Texas, 2004-2010. AB - OBJECTIVE: To examine demographics and trends of financial cost and prominent diseases/conditions resulting in inpatient hospitalizations for infants, children, and adolescents in Texas between 2004 and 2010. METHODS: Longitudinal retrospective cross-sectional study using the Texas Hospital Inpatient Discharge Database, including all pediatric hospitalizations in the state of Texas, 2004 to 2010. RESULTS: Texas has an average of 591 571 pediatric hospitalizations per year. Birth was the most common reason for hospitalization, representing 64% of all pediatric hospitalization annually in Texas. Respiratory illnesses were the most common discharge diagnosis for hospitalized children ages 1 month to 9 years and demonstrated a 2% decrease over the study period. The rate of hospitalizations for digestive conditions and childbirth also demonstrated a decrease over this time frame: 4.7% and 3.0%, respectively. The rate of mental illness diagnoses increased 2.5% over the time frame and represented the most common discharge diagnosis for children aged 10 to 14. Childbirth was the most common reason for hospitalization for adolescents aged 15 to 17 years. There was no increase in total cost of pediatric hospitalizations over the time period under study. CONCLUSIONS: After birth, respiratory illnesses represent the most common reason for hospitalization for children (between 1 month and 10 years of age) in Texas. Mental health conditions and childbirth represent the most common reason for hospitalization for young adolescents (10-14 years) and older adolescents (15-17 years), respectively. PMID- 26136315 TI - Revisiting the History: Hypereosinophilia in a 4-Year-Old With Purpura. PMID- 26136313 TI - Association Between Hyponatremia and Higher Bronchiolitis Severity Among Children in the ICU With Bronchiolitis. AB - BACKGROUND AND OBJECTIVES: It remains unclear whether hyponatremia independently predicts a higher severity of bronchiolitis in children. The objective of this study was to investigate the association between hyponatremia and bronchiolitis severity in children hospitalized in the ICU for bronchiolitis. METHODS: We conducted a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis during the winters of 2007 through 2010. Patients were classified into 2 groups (normonatremic [135-145 mEq/L] and hyponatremic [<135 mEq/L]) based on the first-measured serum sodium concentration on the day of hospitalization. Outcomes were use of mechanical ventilation and ICU length of stay (LOS). To examine the association of sodium status with outcomes, we fit logistic and linear regression models with propensity score adjustment. RESULTS: Of 231 children hospitalized in the ICU for bronchiolitis, 193 (84%) were categorized into the normonatremic group and 38 (16%) into the hyponatremic group. Compared with children with normonatremia, those with hyponatremia had higher risks of mechanical ventilation use (40% vs 58%; P = .04) and longer ICU LOS (median, 3 vs 6 days; P = .007). Likewise, in the adjusted analyses, children with hyponatremia had significantly higher risks of mechanical ventilation use (odds ratio, 2.14 [95% confidence interval, 1.03-4.48; P = .04) and longer ICU LOS (beta-coefficient, 2.21 days [95% confidence interval, 0.68-3.73; P = .005]). CONCLUSIONS: In this prospective, multicenter study of children hospitalized for bronchiolitis, hyponatremia on the day of hospitalization was associated with a higher severity of disease. Our data support hyponatremia as a prognostic factor that might improve the ability of clinicians to predict the disease course of children with severe bronchiolitis. PMID- 26136316 TI - Probability, Uncertainty, and Value in Inpatient Diagnosis: Connecting the Dots. PMID- 26136317 TI - A New Look at Two Old Topics. PMID- 26136318 TI - A universal approach to ultrasmall magneto-fluorescent nanohybrids. AB - Seeded emulsion polymerization is a powerful universal method to produce ultrasmall multifunctional magnetic nanohybrids. In a two-step procedure, iron oxide nanocrystals were initially encapsulated in a polystyrene (PS) shell and subsequently used as beads for a controlled assembly of elongated quantum dots/quantum rods (QDQRs). The synthesis of a continuous PS shell allows the whole construct to be fixed and the composition of the nanohybrid to be tuned. The fluorescence of the QDQRs and magnetism of iron oxide were perfectly preserved, as confirmed by single-particle investigation, fluorescence decay measurements, and relaxometry. Bio-functionalization of the hybrids was straightforward, involving copolymerization of appropriate affinity ligands as shown by immunoblot analysis. Additionally, the universality of this method was shown by the embedment of a broad scale of NPs. PMID- 26136319 TI - Most provider trust finance directors expect performance to be worse than last year's. PMID- 26136320 TI - Determination of eight polyphenols and pantothenic acid in extra-virgin olive oil samples by a simple, fast, high-throughput and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method. AB - A new ultra high performance liquid chromatography coupled with tandem mass spectrometry method for a fast and sensitive determination of eight polyphenols (hydroxytyrosol, catechin, epicatechin, epigallocatechin gallate, oleuropein, quercetin, rutin, tyrosol) and panthotenic acid in extra-virgin olive oil was developed. The method does not require long sample pre-treatment and presents the lowest limit of detection and limit of quantitation values present in literature. Inter- and intra-day variability, linear dynamic range of the calibration curve, recovery and matrix effect were also determined and investigated. The method was applied to several oil samples of different type and origin. Given its accuracy, precision and rapidity, the method is characterized by an interestingly high throughput, reliability, and sensitivity. PMID- 26136321 TI - Label-Free, Electrochemical Quantitation of Potassium Ions from Femtomolar Levels. AB - In this communication, a label-free and sensitive electrochemical method to detect potassium ions is proposed. The conducting polymer polypyrrole was used as both an anchor for the probe and a transducer of the detection event. A K(+) specific G-rich aptamer was applied as a recognition element, which folded into the G-quadruplex structure in the presence of K(+), and this resulted in an increase in the electrode impedance. The combination of the K(+)-selective aptamer and the porous conducting polymer as a signal transducer afforded a successful sensor platform. The sensor responded approximately logarithmically over a wide dynamic range of K(+) concentrations from 20 fM to 1 mM, with a very low detection limit of 14.7 fM and excellent discrimination against other ions. Additionally, electrochemical impedance spectroscopy was used to study the kinetics of K(+) binding at the conducting polymer-immobilized aptamer surface, which indicated strong binding between the two. This work demonstrates a powerful approach for the sensitive, selective, and direct electrochemical detection of metal ions based on the switching conformation of G-rich aptamers attached to a porous conducting polymer surface. This assay scheme can be expanded to the detection of a wide range of targets by modifying the aptamer structure as a recognizing moiety. PMID- 26136322 TI - [Photodynamic Therapy]. PMID- 26136323 TI - [Clinical Application of Indocyanine Green Videoangiography: Current Status and Future Prospects]. PMID- 26136324 TI - [Risk Factors for Adverse Events after Implantation of BCNU Wafers in High-grade Gliomas]. AB - BACKGROUND: In Japan, patients with malignant glioma have been treated with BCNU wafers (Gliadel(r)) since January 2013. Several adverse events(AEs)associated with implantation of BCNU wafers, including cerebral edema or cyst formation, are recognized. Here, we report a retrospective review of the experience with implantation of BCNU wafers in our institutions and our findings regarding the risk factors for the AEs. METHODS: We reviewed the records of patients with malignant glioma who were implanted with BCNU wafers between April 2013 and September 2014. Their AEs were examined clinically and radiologically and evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) grading. For investigating the association between risk factors and incidence of AEs, histological diagnosis, extent of resection, and period of BCNU wafers implantation surgery were selected as possible risk factors. RESULTS: Twenty-one patients were included in this investigation. There were no associations among incidence of AEs and histological diagnosis or extent of tumor resection. However, regarding the period of BCNU wafers implantation, additional resection for newly diagnosed tumors and resection for recurrent tumors tended to increase the rate and severity of AEs, especially cerebral edema, compared to primary resection. CONCLUSION: In cases of BCNU wafers implantation, the incidence and degree of AEs might increase if additional resection for newly diagnosed tumors or resection for recurrent tumors is performed. Our investigation revealed that AEs associated with implantation of BCNU wafers tend to occur in the repeated glioma surgery. PMID- 26136325 TI - [High-Definition Exoscope System for Microneurosurgery:Use of an Exoscope in Combination with Tubular Retraction and Frameless Neuronavigation for Microsurgical Resection of Deep Brain Lesions]. AB - The high-definition exoscope (VITOM(r), Karl Storz GmbH & Co., Tuttlingen, Germany) is a new equipment that can be used as an alternative to the operating microscope in neurosurgery. Several neurosurgeons have recently reported that the exoscope allows for long working distances and great depth of field. Herein, we review reported cases of exoscope use in neurosurgery. We also describe the advantages of the exoscope compared to the operating microscope and endoscope. Furthermore, we introduce a novel technique for microsurgical resection of deep brain lesions, in which the exoscope is used along with tubular retraction and frameless neuronavigation. Before the operation, neuronavigation is registered and the surgical trajectory is planned to avoid damaging the functional cortex and eloquent white matter tracts. By using intraoperative neuronavigation, the tubular retractor (NICO BrainPath(r), NICO Corporation, Indianapolis, US), which is designed to split the white matter when gently inserted, is inserted transcortically into the brain to reach the lesion, along the preplanned trajectory. After insertion, the tubular retractor is fixed in place using a self retaining arm. This creates a narrow corridor that enables the use of the exoscope (for optimum visualization), bimanual dissection technique, and long bayoneted surgical instruments. The large focal distance of the exoscope allows it to be placed sufficiently further away from the surgical site, permitting the passage of long surgical instruments under the scope. Although obtaining surgical access to deep-seated brain lesions is challenging, we consider that this technique facilitates a safe surgical approach for lesions in deep locations. PMID- 26136326 TI - [An Endovascular Approach for Ruptured Aneurysms of the Basilar Trunk Perforating Artery]. AB - Aneurysms of the basilar trunk perforating artery are rarely described in the literature. Only 13 cases have been reported previously. The recommended treatment for these aneurysms is usually direct surgery such as microsurgical clipping or proximal trapping;endovascular therapy is not preferred because of difficulty to access the aneurysm. Recently however, a case report of treatment of basilar trunk perforating aneurysm with a Pipeline Embolization Device was published. Microsurgical clipping or wrapping has the disadvantage of the deep and narrow operative area and the difficult skull-base technique. Here, we report a case of basilar trunk perforating rupture aneurysm and its treatment with endovascular coil embolization. PMID- 26136327 TI - [Progressive Intracranial Hypertension due to Superior Sagittal Sinus Thrombosis Following Mild Head Trauma: A Case Report]. AB - Cerebral venous sinus thrombosis after mild head trauma without skull fracture or intracranial hematoma is exceptionally rare. We describe an unusual case of progressive intracranial hypertension due to superior sagittal sinus thrombosis following mild head trauma. A 17-year-old boy presented with nape pain a day after a head blow during a gymnastics competition (backward double somersault). On admission, he showed no neurological deficit. CT scans revealed no skull fractures, and there were no abnormalities in the brain parenchyma. However, his headache worsened day-by-day and he had begun to vomit. Lumbar puncture was performed on Day 6, and the opening pressure was 40 cm of water. After tapping 20 mL, he felt better and the headache diminished for a few hours. MR venography performed on Day 8 revealed severe flow disturbance in the posterior third of the superior sagittal sinus with multiple venous collaterals. Because of the beneficial effects of lumbar puncture, we decided to manage his symptoms of intracranial hypertension conservatively with repeated lumbar puncture and administration of glycerol. After 7 days of conservative treatment, his symptoms resolved completely, and he was discharged from the hospital. Follow-up MR venography performed on Day 55 showed complete recanalization of the superior sagittal sinus. The exact mechanism of sinus thrombosis in this case is not clear, but we speculate that endothelial damage caused by shearing stress because of strong rotational acceleration or direct impact to the superior sagittal sinus wall may have initiated thrombus formation. PMID- 26136328 TI - [A Girl with Intraorbital Varix: A Case Report]. AB - We report a case of intraorbital varix. A 16-year-old girl showed sudden left sided exophthalmos after vomiting. After several episodes of vomiting, she developed complete loss of vision in the left eye, followed by orbital pain, disruption of eye movement, and periorbital swelling. No change in symptoms or signs was observed after the Valsalva maneuver or jugular vein compression. Computed tomography (CT), magnetic resonance imaging (MRI), and angiography were inconclusive. Transcranial surgery revealed a large varix near the optic nerve. The lesion could not be completely resected because the orbital fat interfered with its complete visualization. We cauterized the lesion to reduce its volume. The patient's symptoms improved markedly after surgery and cauterization. Thus, cauterization appears to be an effective strategy to reduce the volume of an unresectable intraorbital varix. PMID- 26136329 TI - [Two Cases of Primary Intracranial Solitary Fibrous Tumor:Genetic Examination of NAB2-STAT6 Fusion and Its Association with Hemangiopericytoma]. AB - Using whole exome and transcriptome sequencing, NAB2-STAT6 gene fusions have recently been identified in patients with solitary fibrous tumors (SFT). We report two cases of SFT in which NAB2-STAT6 fusions were identified. The patients were a 32-year-old man with a parasagittal tumor involving the superior sagittal sinus, and a 40-year-old man with a cerebellar convexity tumor partially involving the transverse sinus. Their tumors were gross totally resected and diagnosed to be SFT according to the following pathological findings:the tumors were composed of spindle cells with a patternless architecture, with prominent stromal collagen and staghorn vessels. An immunohistochemical study yielded positive results for CD34, CD99, and Bcl-2 and negative results for EMA, GFAP, and S100. The MIB-1 indexes were 13 and 7%, respectively. NAB2-STAT6 fusions were detected in both cases with a common fusion variant, NAB2ex6-STAT6ex16/17. We also identified NAB2-STAT6 fusions in two hemangiopericytomas diagnosed in the past with a common variant of NAB2ex6-STAT6ex16/17. These findings suggest that solitary fibrous tumor and hemangiopericytoma may be diagnosed based on the presence of NAB2-STAT6 fusion, and not classified separately because of the same genetic background. PMID- 26136330 TI - [Delayed Traumatic Intracerebral Hematoma during Antiplatelet Therapy after Operations for Ruptured Left ICPC Aneurysm and Right Traumatic Epidural Hematoma: A Case Report]. AB - Delayed traumatic intracerebral hematoma (DTICH) is a rare complication of head injury that appears suddenly after an interval of several days or months. Here, we report a case of DTICH during antiplatelet therapy for vasospasm following surgeries for a ruptured left internal carotid-posterior communicating (ICPC) aneurysm and right acute epidural hematoma (EDH). A 77-year-old man with no medical history was diagnosed with a subarachnoid hemorrhage (SAH) due to rupturing of a left ICPC aneurysm and a right linear fracture of the right parietal bone due to a head injury following the rupture. On day 2, the patient underwent successful clipping of the left ICPC aneurysm. Computed tomography (CT) performed post-clipping revealed a right acute EDH below the linear fracture of the right parietal bone, which was removed immediately. A next-day CT revealed minor contusions in both temporal poles. Fasudil, ozagrel, and cilostazol were administered from Day 3 post-clipping and EDH evacuation to prevent vasospasm. The contusions did not enlarge until Day 10. On Day 11, the patient became comatose, and a huge hematoma was identified in the right temporal lobe to frontal lobe. Although the hematoma was removed immediately, the patient died on Day 13. The hematoma was considered to be a rare case of DTICH that developed from a minor contusion of the right temporal lobe during antiplatelet therapy for vasospasm. In cases of aneurysmal SAH with head injury and contusion, we must pay attention to DTICH and select more deliberate treatment for vasospasm. PMID- 26136331 TI - [Required Knowledge for Stroke Specialists (12) Stroke Rehabilitation]. PMID- 26136332 TI - [How to Make a New Life in Japan for Neurosurgical Training: The Ways to Academics Success & Effectiveness]. PMID- 26136333 TI - Suzy Lishman: Grateful to the air bubble. PMID- 26136334 TI - A Native Ternary Complex Trapped in a Crystal Reveals the Catalytic Mechanism of a Retaining Glycosyltransferase. AB - Glycosyltransferases (GTs) comprise a prominent family of enzymes that play critical roles in a variety of cellular processes, including cell signaling, cell development, and host-pathogen interactions. Glycosyl transfer can proceed with either inversion or retention of the anomeric configuration with respect to the reaction substrates and products. The elucidation of the catalytic mechanism of retaining GTs remains a major challenge. A native ternary complex of a GT in a productive mode for catalysis is reported, that of the retaining glucosyl-3 phosphoglycerate synthase GpgS from M. tuberculosis in the presence of the sugar donor UDP-Glc, the acceptor substrate phosphoglycerate, and the divalent cation cofactor. Through a combination of structural, chemical, enzymatic, molecular dynamics, and quantum-mechanics/molecular-mechanics (QM/MM) calculations, the catalytic mechanism was unraveled, thereby providing a strong experimental support for a front-side substrate-assisted SN i-type reaction. PMID- 26136335 TI - An Individual-Based Simulation Approach to the Evolution of Locomotor Performance. AB - Maximal whole-organism performance traits measured in the laboratory and the levels of performance expressed in the field often exhibit a mismatch, complicating our understanding of the selection pressures influencing the evolution of performance traits. To better understand the evolution of locomotor performance, we built an individual-based simulation to test hypotheses about selection on locomotor performance. Starting with a population of individuals with two correlated but variable performance traits, we simulated these individuals surviving and reproducing in a complex environment, presenting each individual with successive ecological challenges requiring specific performance capabilities over their lifespan. While most challenges require sub-maximal speeds, intermittent bouts requiring increased performance, such as escape from predators, introduce strong, but infrequent, selection for maximal performance. By comparing the results of simulations run with individuals that only perform at their maximum levels versus those that adjust this effort, we show that intra individual variation in speed confers a selective advantage, regardless of the extent of that variation. We also show that the direction and strength of the correlation between the two performance traits affects the evolutionary trajectory of phenotypic change. Ultimately, this model allows us to simulate the evolution of movement speeds over a range of selective contexts, offering insight into the factors affecting the evolutionary relationship between optimal and maximal performance. PMID- 26136336 TI - Exoskeletons across the Pancrustacea: Comparative Morphology, Physiology, Biochemistry and Genetics. AB - The exoskeletons of pancrustaceans, as typified by decapod crustaceans and insects, demonstrate a high degree of similarity with respect to histology, ultrastructure, function, and composition. The cuticular envelope in insects and the outer epicuticle in crustaceans both serve as the primary barrier to permeability of the exoskeleton, preventing loss of water and ions to the external medium. Prior to and following ecdysis, there is a sequence of expression and synthesis of different proteins by the cuticular epithelium for incorporation into the pre-exuvial and post-exuvial procuticle of insects and the exocuticle and endocuticle of crustaceans. Both exhibit regional differences in cuticular composition, e.g., the articular (intersegmental) membranes of insects and the arthrodial (joint) membranes of crustaceans. The primary difference between these cuticles is the ability to mineralize. Crustaceans' cuticles express a unique suite of proteins that provide for the nucleation and deposition of calcium carbonate. Orthologs of genes discussed in the present review were mined from a recently completed cuticular transcriptome of the crayfish, Cherax quadricarinatus, providing new insights into the nature of these proteins. PMID- 26136337 TI - Radiosensitization and downregulation of heterogeneous nuclear ribonucleoprotein K (hnRNP K) upon inhibition of mitogen/extracellular signal-regulated kinase (MEK) in malignant melanoma cells. AB - BACKGROUND: Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is an important cofactor in the p53-mediated DNA damage response pathway upon ionizing radiation (IR) and exerts anti-apoptotic effects also independent of p53 pathway activation. Furthermore, hnRNP K is overexpressed in various neoplasms including malignant melanoma (MM). Here, we investigate the role of hnRNP K in the radioresistance of MM cells. METHODS AND RESULTS: Our results show cytoplasmic expression of hnRNP K in human MM surgical specimens, but not in benign nevi, and a quick dose- and time-dependent upregulation in response to IR accompanied by cytoplasmic redistribution of the protein in the IPC-298 cellular tumor model carrying an activating NRAS mutation (p.Q61L). SiRNA-based knockdown of hnRNP K induced a delayed decline in gammaH2AX/53BP1-positive DNA repair foci upon IR. Pharmacological interference with MAPK signaling abrogated ERK phosphorylation, diminished cellular hnRNP K levels, impaired gammaH2AX/53BP1-foci repair and proliferative capability and increased apoptosis comparable to the observed hnRNP K knockdown phenotype in IPC-298 cells. CONCLUSIONS: Our results indicate that pharmacological interference with MAPK signaling increases vulnerability of NRAS mutant malignant melanoma cells to ionizing radiation along with downregulation of endogenous hnRNP K and point towards a possible use for combined MEK inhibition and localized radiation therapy of MM in the NRAS-mutant setting where BRAF inhibitors offer no clinical benefit. PMID- 26136338 TI - Role and prognostic significance of the epithelial-mesenchymal transition factor ZEB2 in ovarian cancer. AB - ZEB2 is a key factor in epithelial-mesenchymal transition (EMT), a program controlling cell migration in embryonic development and adult tissue homeostasis. We demonstrated a role of ZEB2 in migration and anchorage-independent cell growth in ovarian cancer, as shown by ZEB2 silencing. We found that the RNA-binding protein HuR bound the 3'UTR of ZEB2 mRNA, acting as a positive regulator of ZEB2 protein expression. In Hey ovarian cell line, HuR silencing decreased ZEB2 and ZEB1 nuclear expression and impaired migration. In hypoglycemic conditions ZEB2 expression decreased, along with ZEB1, vimentin and cytoplasmic HuR, and a reduced cellular migration ability was observed. Analysis of ZEB2 and HuR expression in ovarian cancers revealed that nuclear ZEB2 is localized in tumor leading edge and co-localizes with cytoplasmic HuR. In a series of 143 ovarian cancer patients high expression of ZEB2 mRNA significantly correlated with a poor prognosis in term of both overall survival and progression- free survival. Moreover, at immunohistochemical evaluation, we found that prognostic significance of ZEB2 protein relies on its nuclear expression and co-localization with cytoplasmic HuR. In conclusion our findings indicated that nuclear ZEB2 may enhance progression of EMT transition and acquisition of an aggressive phenotype in ovarian cancer. PMID- 26136339 TI - Cynara scolymus affects malignant pleural mesothelioma by promoting apoptosis and restraining invasion. AB - Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors similarly to pemetrexed, a commonly employed drug in the treatment of mesothelioma. In aggregate our findings suggest that leaf extract of Cynara scolymus holds therapeutic potential for the treatment of mesothelioma. PMID- 26136340 TI - 5mC-hydroxylase activity is influenced by the PARylation of TET1 enzyme. AB - 5-hydroxymethylcytosine is a new epigenetic modification deriving from the oxidation of 5-methylcytosine by the TET hydroxylase enzymes. DNA hydroxymethylation drives DNA demethylation events and is involved in the control of gene expression. Deregulation of TET enzymes causes developmental defects and is associated with pathological conditions such as cancer. Little information thus far is available on the regulation of TET activity by post-translational modifications. Here we show that TET1 protein is able to interact with PARP 1/ARTD1 enzyme and is target of both noncovalent and covalent PARylation. In particular, we have demonstrated that the noncovalent binding of ADP-ribose polymers with TET1 catalytic domain decreases TET1 hydroxylase activity while the covalent PARylation stimulates TET1 enzyme. In addition, TET1 activates PARP 1/ARTD1 independently of DNA breaks. Collectively, our results highlight a complex interplay between PARylation and TET1 which may be helpful in coordinating the multiple biological roles played by 5-hydroxymethylcytosine and TET proteins. PMID- 26136342 TI - Asymmetric Total Synthesis of (-)-Maoecrystal V. AB - The asymmetric total synthesis of (-)-maoecrystal V, a novel cytotoxic pentacyclic ent-kaurane diterpene, has been accomplished. Key steps of the current strategy involve an early-stage semipinacol rearrangement reaction for the construction of the C10 quaternary stereocenter, a rhodium-catalyzed intramolecular O-H insertion reaction, and a sequential Wessely oxidative dearomatization/intramolecular Diels-Alder reaction to forge the pentacyclic framework of maoecrystal V. PMID- 26136346 TI - Asymmetric Construction of Spirooxindoles by Organocatalytic Multicomponent Reactions Using Diazooxindoles. AB - The first highly diastereo- and enantioselective multicomponent reaction of diazooxindoles, nitrosoarenes, and nitroalkenes using a newly developed hydrogen bond catalyst has been successfully developed for the efficient construction of a series of spirooxindole derivatives with excellent functional-group tolerance. Spirooxindoles are formed in excellent yields and stereoselectivities, and the method represents an unprecedented approach for trapping the active intermediate with a nitroalkene to form biologically important compounds having three contiguous stereogenic centers with excellent asymmetric induction. PMID- 26136341 TI - A NOX2/Egr-1/Fyn pathway delineates new targets for TKI-resistant malignancies. AB - Tyrosine kinase inhibitors (TKI) have improved CML response rates, and some are effective against resistance-promoting point mutations in BCR-ABL1. However, in the absence of point mutations, resistance still occurs. Here, we identify a novel pathway mediating resistance which connects p47phox, the organizer subunit of NADPH oxidase-2 (NOX2), with early growth response-1 (Egr-1) and the Src family kinase Fyn. We found up-regulation of p47phox, Egr-1, and Fyn mRNA and protein using paired isogenic CML cell lines and mined data. Isolation of CD34+ cells and tissue microarray staining from blast crisis CML patients confirmed in vivo over-expression of components of this pathway. Knockdown studies revealed that p47phox modulated reactive oxygen species and Egr-1 expression, which, in turn, controlled Fyn expression. Interestingly, Fyn knockdown sensitized TKI resistant cells to dasatinib, a dual BCR-ABL1/Src inhibitor. Egr-1 knockdown had similar effects, indicating the utility of targeting Fyn expression over activation. Pointedly, p47phox knockdown also restored TKI-sensitivity, indicating that targeting the NOX2 complex can overcome resistance. The NOX2/Egr 1/Fyn pathway was also conserved within TKI-resistant EGFRDeltaIII-expressing glioblastoma and patient-derived glioblastoma stem cells. Thus, our findings suggest that targeting the NOX2/Egr-1/Fyn pathway may have clinical implications within multiple cancer types; particularly where efficacy of TKI is compromised. PMID- 26136347 TI - NiSe Nanowire Film Supported on Nickel Foam: An Efficient and Stable 3D Bifunctional Electrode for Full Water Splitting. AB - Active and stable electrocatalysts made from earth-abundant elements are key to water splitting for hydrogen production through electrolysis. The growth of NiSe nanowire film on nickel foam (NiSe/NF) in situ by hydrothermal treatment of NF using NaHSe as Se source is presented. When used as a 3D oxygen evolution electrode, the NiSe/NF exhibits high activity with an overpotential of 270 mV required to achieve 20 mA cm(-2) and strong durability in 1.0 M KOH, and the NiOOH species formed at the NiSe surface serves as the actual catalytic site. The system is also highly efficient for catalyzing the hydrogen evolution reaction in basic media. This bifunctional electrode enables a high-performance alkaline water electrolyzer with 10 mA cm(-2) at a cell voltage of 1.63 V. PMID- 26136348 TI - End pharmacists' monopoly on selling certain drugs. PMID- 26136349 TI - Catalytic Ring Expansion of Cyclic Hemiaminals for the Synthesis of Medium-Ring Lactams. AB - A mild and efficient intermolecular ring-expansion approach was developed for the synthesis of medium-ring lactams by using siloxy alkynes. Key to success is the suitable combination of a superior catalyst and an exceptional nitrogen protecting group. Control experiments indicated that the reaction is remarkably selective toward the desired lactam formation, even with many possible non productive pathways. PMID- 26136350 TI - Host-Guest Complexation of Perethylated Pillar[5]arene with Alkanes in the Crystal State. AB - Activated perethylated pillar[5]arene crystals show an unexpected alkane-shape- and -length-selective gate-opening behavior. Activated crystals were obtained upon removing solvents from perethylated pillar[5]arene crystals by heating. The activated crystals could quantitatively take up n-alkanes with carbon chains containing more than five carbon atoms as a consequence of their gate-opening pressure. As the chain length of the n-alkanes increased, the gate pressure decreased. A transformation into a herringbone structure was induced when n hexane was used as a guest. By contrast, cyclic and branched alkanes were not taken up and could not induce a crystal transformation because they were too large to fit in the cavities of the pillar[5]arene. Alkane-shape-selective molecular recognition of pillar[5]arenes in the solution state was translated into the vapor/crystal state. PMID- 26136352 TI - FAS Gene Copy Numbers are Associated with Susceptibility to Behcet Disease and VKH Syndrome in Han Chinese. AB - Previous studies have identified that disturbed apoptosis was involved in the pathogenesis of Behcet disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome. This study aims to investigate whether copy number variations of apoptosis-related genes, including FAS, CASPASE8, CASPASE3, and BCL2, are associated with BD and VKH syndrome in Han Chinese. A two-stage association study was performed in 1,014 BD patients, 1,051 VKH syndrome patients, and 2,076 healthy controls. TaqMan((r)) Copy Number Assays and real-time PCR were performed. The first-stage study showed that increased frequency of high FAS copy number (>2) was found in BD (P = 1.05 * 10(-3) ) and VKH syndrome (P = 2.56 * 10(-3) ). Replication and combined study confirmed the association of high copy number (>2) of FAS with BD (P = 3.35 * 10( 8) ) and VKH syndrome (P = 9.77 * 10(-8) ). A significant upregulated mRNA expression of FAS was observed in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells from individuals carrying a high gene copy number (>2) as compared to normal diploid 2 copy number carriers (P = 0.004). Moreover, the mRNA expression of FAS both in active patients with BD and VKH syndrome was significantly higher than that in controls (P = 0.001 and P = 0.007, respectively). Our findings suggest that a high copy number of FAS gene confers risk for BD and VKH syndrome. PMID- 26136351 TI - Waiting Impulsivity: The Influence of Acute Methylphenidate and Feedback. AB - BACKGROUND: The ability to wait and to weigh evidence is critical to behavioral regulation. These behaviors are known as waiting and reflection impulsivity. In Study 1, we examined the effects of methylphenidate, a dopamine and norepinephrine reuptake inhibitor, on waiting and reflection impulsivity in healthy young individuals. In study 2, we assessed the role of learning from feedback in disorders of addiction. METHODS: We used the recently developed 4 Choice Serial Reaction Time task and the Beads task. Twenty-eight healthy volunteers were tested twice in a randomized, double-blind, placebo-controlled cross-over trial with 20mg methylphenidate. In the second study, we analyzed premature responses as a function of prior feedback in disorders of addiction. RESULTS: Study 1: Methylphenidate was associated with greater waiting impulsivity to a cue predicting reward along with faster responding to target onset without a generalized effect on reaction time or attention. Methylphenidate influenced reflection impulsivity based on baseline impulsivity. Study 2: More premature responses occurred after premature responses in stimulant-dependent subjects. CONCLUSIONS: We show that methylphenidate has dissociable effects on waiting and reflection impulsivity. Chronic stimulant exposure impairs learning from prior premature responses, suggesting a failure to learn that premature responding is suboptimal. These findings provide a greater mechanistic understanding of waiting impulsivity. PMID- 26136355 TI - Biomineralization of a Cadmium Chloride Nanocrystal by a Designed Symmetrical Protein. AB - We have engineered a metal-binding site into the novel artificial beta-propeller protein Pizza. This new Pizza variant carries two nearly identical domains per polypeptide chain, and forms a trimer with three-fold symmetry. The designed single metal ion binding site lies on the symmetry axis, bonding the trimer together. Two copies of the trimer associate in the presence of cadmium chloride in solution, and very high-resolution X-ray crystallographic analysis reveals a nanocrystal of cadmium chloride, sandwiched between two trimers of the protein. This nanocrystal, containing seven cadmium ions lying in a plane and twelve interspersed chloride ions, is the smallest reported to date. Our results indicate the feasibility of using rationally designed symmetrical proteins to biomineralize nanocrystals with useful properties. PMID- 26136356 TI - Chronic obstructive pulmonary disease: missed diagnosis versus misdiagnosis. PMID- 26136357 TI - Approach Bias Modification in Food Craving-A Proof-of-Concept Study. AB - The aim of the present proof-of-concept study was to test a novel cognitive bias modification (CBM) programme in an analogue sample of people with subclinical bulimic eating disorder (ED) psychopathology. Thirty participants with high levels of trait food craving were trained to make avoidance movements in response to visual food stimuli in an implicit learning paradigm. The intervention comprised ten 15-minute sessions over a 5-week course. At baseline, participants showed approach and attentional biases towards high-caloric palatable food that were both significantly reduced and turned into avoidance biases after the training. Participants also reported pronounced reductions in both trait and cue elicited food craving and in ED symptoms as well. The overall evaluation of the training by the participants was positive. The specific CBM programme tested in this pilot trial promises to be an effective and feasible way to alter automatic action tendencies towards food in people suffering from bulimic ED psychopathology. PMID- 26136359 TI - Post-Assembly Stabilization of Rationally Designed DNA Crystals. AB - This manuscript reports an effort to stabilize self-assembled DNA crystals. Owing to their weak inter-unit cohesion, self-assembled DNA crystals are fragile, which limits the potential applications of such crystals. To overcome this problem, another molecule was introduced, which binds to the cohesive sites and stabilizes the inter-unit interactions. The extra interactions greatly improve the stability of the DNA crystals. The original DNA crystals are only stable in solutions of high ionic strength (e.g., >=1.2 M (NH4)2SO4); in contrast, the stabilized crystals can be stable at ionic strengths as low as that of a 0.02 M solution of (NH4)2SO4. The current strategy is expected to represent a general approach for increasing the stability of self-assembled DNA nanostructures for potential applications, for example, as structural scaffolds and molecular sieves. PMID- 26136358 TI - TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse. AB - Genome-wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11, an X-linked meiosis-specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX11 is mutated in infertile men with non-obstructive azoospermia and that an analogous mutation in the mouse impairs meiosis. Genetic screening of a large cohort of idiopathic infertile men reveals that TEX11 mutations, including frameshift and splicing acceptor site mutations, cause infertility in 1% of azoospermic men. Functional evaluation of three analogous human TEX11 missense mutations in transgenic mouse models identified one mutation (V748A) as a potential infertility allele and found two mutations non-causative. In the mouse model, an intronless autosomal Tex11 transgene functionally substitutes for the X-linked Tex11 gene, providing genetic evidence for the X-to-autosomal retrotransposition evolution phenomenon. Furthermore, we find that TEX11 protein levels modulate genome-wide recombination rates in both sexes. These studies indicate that TEX11 alleles affecting expression level or substituting single amino acids may contribute to variations in recombination rates between sexes and among individuals in humans. PMID- 26136360 TI - Central Coherence, Visuoconstruction and Visual Memory in Patients with Eating Disorders as Measured by Different Scoring Methods of the Rey Complex Figure Test. AB - OBJECTIVE: The aims of this study were to examine the performance of eating disorder (ED) patients on the Rey Complex Figure Test and to investigate the validity of the Q-score as a new method for measuring central coherence (CC). METHOD: Forty-one patients with anorexia nervosa, 40 patients with bulimia nervosa and 40 healthy controls completed the Rey Complex Figure Test, which was scored both quantitatively and qualitatively. RESULTS: Both ED groups scored lower than the healthy controls on copy, recall and the Q-score. For the anorexia nervosa group, performance on the Central Coherence Index was associated with the nadir body mass index. Performance on the recall measures was independently associated with the nadir body mass index and depressive symptoms for the bulimia nervosa group. There was a strong correlation between the Q-score and the Central Coherence Index (r = 0.77). DISCUSSION: The study reveals different levels of CC and suggests that the Q-score might be an applicable method for measuring CC in ED patients. PMID- 26136361 TI - Topic controversies in the endoscopic management of malignant hilar strictures using metal stent: side-by-side versus stent-in-stent techniques. AB - Endoscopic management of unresectable hilar malignant biliary stricture (MBS) is currently challenging, and the best approach is still controversial. Liver volume is the key to adequate biliary drainage in hilar MBS and multiple stenting is mandatory to drain over 50% of liver volume in most cases. The self-expandable metallic stent (SEMS) has shown superior patency to plastic stents in recent reports. There are two methods of multiple stenting for hilar MBS: stent-in-stent (SIS) and side-by-side (SBS). Advantages of SIS include multiple SEMS placement in one stent caliber at the common bile duct (CBD), which is considered physiologically ideal. The through-the-mesh (TTM) technique with guidewires and the SEMS delivery system can be technically difficult in SIS, although the recent development of dedicated SEMSs having a loose portion facilitating the TTM technique makes SIS technically feasible both at stent deployment and re interventions. Conversely, the SBS technique, if placed across the papilla, is technically simple at initial placement and re-intervention at stent occlusion. However, SBS has potential disadvantages of overexpansion of the CBD because of parallel placement of multiple SEMS, which can lead to portal vein thrombosis. Given the limited evidence available, a well-designed randomized controlled trial comparing these two techniques is warranted. PMID- 26136362 TI - Estimating the computational limits of detection of microbial non-model organisms. AB - Mass spectrometry has become a key instrument for proteomic studies of single bacteria as well as microbial communities. However, the identification of spectra from MS/MS experiments is still challenging, in particular for non-model organisms. Due to the limited amount of related protein reference sequences, underexplored organisms often remain completely unidentified or their spectra match to peptides of uncertain degree of relation. Alternative strategies such as error-tolerant spectra searches or proteogenomic approaches may reduce the amount of unidentified spectra and lead to peptide matches on more related taxonomic levels. However, to what extent these strategies may be successful is difficult to judge prior to an MS/MS experiment. In this contribution, we introduce a method to estimate the suitability of databases of interest. Further, it allows estimating the possible influence of error-tolerant searches and proteogenomic approaches on databases of interest with respect to the number of unidentified spectra and the taxonomic distances of identified spectra. Furthermore, we provide an implementation of our approach that supports experimental design by evaluating the benefit and need of different search strategies with respect to present databases and organisms under study. We provide several examples which highlight the different effects of additional search strategies on databases and organisms with varying amount of known relative species available. PMID- 26136363 TI - A role for Rab23 in the trafficking of Kif17 to the primary cilium. AB - The small GTPase Rab23 is an antagonist of sonic hedgehog (Shh) signaling during mouse development. Given that modulation of Shh signaling depends on the normal functioning of the primary cilium, and overexpression of Evi5L, a putative Rab23 GTPase-activating protein (GAP), leads to reduced ciliogenesis, Rab23 could have a role at the primary cilium. Here, we found that wild-type Rab23 and the constitutively active Rab23 Q68L mutant were enriched at the primary cilium. Therefore, we tested the role of Rab23 in the ciliary targeting of known cargoes and found that ciliary localization of the kinesin-2 motor protein Kif17 was disrupted in Rab23-depleted cells. Co-immunoprecipitation and affinity-binding studies revealed that Rab23 exists in a complex with Kif17 and importin beta2 (the putative Kif17 ciliary import carrier), implying that Kif17 needs to bind to regulatory proteins like Rab23 for its ciliary transport. Although a ciliary cytoplasmic gradient of nuclear Ran is necessary to regulate the ciliary transport of Kif17, Rab23 and Ran appear to have differing roles in regulating the ciliary entry of Kif17. Our findings have uncovered a hitherto unknown effector of Rab23 and demonstrate how Rab23 could mediate the transport of Kif17 to the primary cilium. PMID- 26136365 TI - Transport of the cholera toxin B-subunit from recycling endosomes to the Golgi requires clathrin and AP-1. AB - The retrograde pathway is defined by the transport of proteins and lipids from the plasma membrane through endosomes to the Golgi complex, and is essential for a variety of cellular activities. Recycling endosomes are important sorting stations for some retrograde cargo. SMAP2, a GTPase-activating protein (GAP) for Arf1 with a putative clathrin-binding domain, has previously been shown to participate in the retrograde transport of the cholera toxin B-subunit (CTxB) from recycling endosomes. Here, we found that clathrin, a vesicle coat protein, and clathrin adaptor protein complex 1 (AP-1) were present at recycling endosomes and were needed for the retrograde transport of CTxB from recycling endosomes to the Golgi, but not from the plasma membrane to recycling endosomes. SMAP2 immunoprecipitated clathrin and AP-1 through a putative clathrin-binding domain and a CALM-binding domain, and SMAP2 mutants that did not interact with clathrin or AP-1 could not localize to recycling endosomes. Moreover, knockdown of Arf1 suppressed the retrograde transport of CTxB from recycling endosomes to the Golgi. These findings suggest that retrograde transport is mediated by clathrin coated vesicles from recycling endosomes and that the role of the coat proteins is in the recruitment of Arf GAP to transport vesicles. PMID- 26136364 TI - RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells. AB - Vasculogenesis and angiogenesis are controlled by vascular endothelial growth factor A (VEGF-A). Dysregulation of these physiological processes contributes to the pathologies of heart disease, cancer and stroke. Rho GTPase proteins play an integral role in VEGF-mediated formation and maintenance of blood vessels. The regulatory functions of RhoA and RhoB in vasculogenesis and angiogenesis are well defined, whereas the purpose of RhoC remains poorly understood. Here, we describe how RhoC promotes vascular homeostasis by modulating endothelial cell migration, proliferation and permeability. RhoC stimulates proliferation of human umbilical vein endothelial cells (HUVECs) by stabilizing nuclear beta-catenin, which promotes transcription of cyclin D1 and subsequently drives cell cycle progression. RhoC negatively regulates endothelial cell migration through MAPKs and downstream MLC2 signaling, and decreases vascular permeability through downregulation of the phospholipase Cgamma (PLCgamma)-Ca(2+)-eNOS cascade in HUVECs. Using a VEGF-inducible zebrafish (Danio rerio) model, we observed significantly increased vascular permeability in RhoC morpholino (MO)-injected zebrafish compared with control MO-injected zebrafish. Taken together, our findings suggest that RhoC is a key regulator of vascular homeostasis in endothelial cells. PMID- 26136366 TI - The importance of indifference in scientific research. AB - Current issues regarding scientific ethics have focused for the most part on regulations governing research and publication. I suggest that the internal process by which we separate self interest from the scientific process is a crucial and neglected part of training. Consideration of these issues might help us train better scientists instead of just scientists who adhere to the rules.This is a follow-up to the essay 'The importance of stupidity in scientific research' by Martin A. Schwartz (J. Cell Sci. 121, 1771). PMID- 26136367 TI - Are prolific authors too much of a good thing? PMID- 26136368 TI - CuI and H2 O2 Inactivate and FeII Inhibits [Fe]-Hydrogenase at Very Low Concentrations. AB - [Fe]-Hydrogenase (Hmd) catalyzes reversible hydride transfer from H2 . It harbors an iron-guanylylpyridinol as a cofactor with an FeII that is ligated to one thiolate, two COs, one acyl-C, one pyridinol-N, and solvent. Here, we report that CuI and H2 O2 inactivate Hmd (half-maximal rates at 1 MUM CuI and 20 MUM H2 O2 ) and that FeII inhibits the enzyme with very high affinity (Ki =40 nM). Infrared and EPR studies together with competitive inhibition studies with isocyanide indicated that CuI exerts its inhibitory effect most probably by binding to the active site iron-thiolate ligand. Using the same methods, it was found that H2 O2 binds to the active-site iron at the solvent-binding site and oxidizes FeII to FeIII . Also it was shown that FeII reversibly binds away from the active site iron, with binding being competitive to the organic hydride acceptor; this inhibition is specific for FeII and is reminiscent of that for the [FeFe] hydrogenase second iron, which specifically interacts with H2 . PMID- 26136369 TI - Social Rank, Rank-Related Life Events and Eating Pathology. AB - BACKGROUND: This study explored the role of meaning in the link between stress and disordered eating, in particular focusing on social rank. METHOD: Two hundred and eleven women completed measures of eating pathology, depression, social comparison and life events where life events were assessed in terms of general loss, threat, shame and loss of social status. RESULTS: Events involving loss of social status were related to eating pathology but only in women reporting self perceived low rank. Events that did not concern social status were unrelated to eating pathology. DISCUSSION: Women who perceive themselves to be low social status appear vulnerable to events that concern their social status. PMID- 26136370 TI - Ruthenium-Catalyzed Monoalkenylation of Aromatic Ketones by Cleavage of Carbon Heteroatom Bonds with Unconventional Chemoselectivity. AB - Ruthenium-catalyzed selective monoalkenylation of ortho C-O or C-N bonds of aromatic ketones was achieved. The reaction allowed the direct comparison of the relative reactivities of the cleavage of different carbon-heteroatom bonds, thus suggesting an unconventional chemoselectivity, where smaller, more-electron donating groups are more easily cleaved. Selective monofunctionalization of C-O bonds in the presence of ortho C-H bonds was also achieved. PMID- 26136371 TI - Biweekly gemcitabine plus S-1 for locally advanced and metastatic pancreatic cancer: a preliminary feasibility study. AB - BACKGROUND: Chemotherapy for unresectable pancreatic cancer should not only prolong survival but maintain quality of life, considering its limited life expectancy. To achieve these goals, biweekly gemcitabine plus S-1 was assessed in the clinical practice setting. METHODS: Fifty-two patients with either locally advanced or metastatic pancreatic cancer who received biweekly gemcitabine plus S 1 as a first-line anti-cancer treatment were included in this study. Treatment delivery, toxicity, response, and survival were reviewed to assess the feasibility and efficacy. RESULTS: The completion rate of treatment delivery was 95.1%, with relative dose intensity of 97.1% for gemcitabine and 97.3% for S-1. Overall, grade 3 or worse adverse events were rare, with hematologic toxicities occurring in 5.8%. The objective response rate was 30.8%, and more than a 50% reduction of CA19-9 was observed in 77.1%. Surgical conversion was completed with a margin-negative resection in four patients whose tumor had shrunk for at least 6 months. The median progression-free and overall survivals were 10.4 and 18.2 months, respectively. Reduction of CA19-9 was associated with longer survival. CONCLUSIONS: Biweekly gemcitabine plus S-1 may be a good alternative to current standard chemotherapies for unresectable pancreatic cancer with less toxicity and less treatment burden without losing efficacy. PMID- 26136372 TI - A New Hyaluronic Acid Derivative Obtained from Atom Transfer Radical Polymerization as a siRNA Vector for CD44 Receptor Tumor Targeting. AB - Two derivatives of hyaluronic acid (HA) have been synthesized by atom transfer radical polymerization (ATRP), starting from an ethylenediamino HA derivative (HA EDA) and by using diethylaminoethyl methacrylate (DEAEMA) as a monomer for polymerization. Both samples, indicated as HA-EDA-pDEAEMA a and b, are able to condense siRNA, as determined by gel retardation assay and resulting complexes show a size and a zeta potential value dependent on polymerization number, as determined by dynamic light scattering measurements. In vitro studies performed on HCT 116 cell line, that over express CD44 receptor, demonstrate a receptor mediated uptake of complexes, regardless of their surface charge. PMID- 26136373 TI - Covalent functionalization of HiPco single-walled carbon nanotubes: differences in the oxidizing action of H2 SO4 and HNO3 during a soft oxidation process. AB - The results of a study on the evolution of HiPco single-walled carbon nanotubes during the oxidizing action of H2 SO4 and HNO3 are presented. The process conditions used have been chosen so as to avoid any significant damage to the nanotube structure. The type and level of functionalization, the location of the grafted functions on the surface of the nanotube and the changes in morphological characteristics of the samples were examined by using a wide and complementary range of analytical techniques. We propose an explanation for the differences in the oxidizing action of sulfuric and nitric acids. The combined results allow us to suggest possible reaction mechanisms that occur on the surface of the nanotube. PMID- 26136375 TI - Dehydrative Direct C-H Allylation with Allylic Alcohols under [Cp*Co(III)] Catalysis. AB - The unique reactivity of [Cp*Co(III)] over [Cp*Rh(III)] was demonstrated. A cationic [Cp*Co(III)] catalyst promoted direct dehydrative C-H allylation with non-activated allyl alcohols, thus giving C2-allylated indoles, pyrrole, and phenyl-pyrazole in good yields, while analogous [Cp*Rh(III)] catalysts were not effective. The high gamma-selectivity and C2-selectivity indicated that the reaction proceeded by directing-group-assisted C-H metalation. DFT calculations suggested that the gamma-selective substitution reaction proceeded by C-H metalation and insertion of a C-C double bond, with subsequent beta-hydroxide elimination. The [Cp*Co(III)] catalyst favored beta-hydroxide elimination over beta-hydride elimination. PMID- 26136374 TI - Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis. AB - Although the two catalytic subunits of the SWI/SNF chromatin-remodeling complex- Brahma (Brm) and Brg1--are almost invariably co-expressed, their mutually exclusive incorporation into distinct SWI/SNF complexes predicts that Brg1- and Brm-based SWI/SNF complexes execute specific functions. Here, we show that Brg1 and Brm have distinct functions at discrete stages of muscle differentiation. While Brg1 is required for the activation of muscle gene transcription at early stages of differentiation, Brm is required for Ccnd1 repression and cell cycle arrest prior to the activation of muscle genes. Ccnd1 knockdown rescues the ability to exit the cell cycle in Brm-deficient myoblasts, but does not recover terminal differentiation, revealing a previously unrecognized role of Brm in the activation of late muscle gene expression independent from the control of cell cycle. Consistently, Brm null mice displayed impaired muscle regeneration after injury, with aberrant proliferation of satellite cells and delayed formation of new myofibers. These data reveal stage-specific roles of Brm during skeletal myogenesis, via formation of repressive and activatory SWI/SNF complexes. PMID- 26136376 TI - A xeno-free microcarrier-based stirred culture system for the scalable expansion of human mesenchymal stem/stromal cells isolated from bone marrow and adipose tissue. AB - Human mesenchymal stem/stromal cells (MSC) are promising candidates for cell based therapies and the development of microcarrier-based cultures in scalable bioreactors with well-defined xenogeneic-free components represent important milestones towards the clinical-scale production of these cells. In this work, we optimized our previously developed xeno-free microcarrier-based system for the scalable expansion of human MSC isolated from bone marrow (BM MSC) and adipose derived stem/stromal cells (ASC). By adapting the agitation/feeding protocol at the initial cell seeding/cultivation stage in spinner flasks, we were able to maximize cell expansion rate and final cell yield. Maximal cell densities of 3.6 * 10(5) and 1.9 * 10(5) cells/mL were obtained for BM MSC (0.60 +/- 0.04 day(-1) ) and ASC (0.9 +/- 0.1 day(-1) ) cultures, upon seven and eight days of cultivation, respectively. Ready-to-use microcarriers Synthemax(r) II and Enhanced Attachment(r) supported identical expansion performance of BM MSC, turning those effective alternatives to the pre-coated plastic microcarriers used in our xeno-free scalable culture system. Importantly, expanded MSC maintained their immunophenotype and multilineage differentiation potential. Moreover, secretome analysis suggested a priming effect of stirred culture conditions on cytokine production by MSC. This culture system yielded considerable final cell densities that can be scaled-up to controlled large-scale bioreactors allowing a more efficient, safe and cost-effective MSC production for clinical settings. PMID- 26136377 TI - Neuroprotective effects of alpha-melanocyte-stimulating hormone against the neurotoxicity of 1-methyl-4-phenylpyridinium. AB - Parkinson's disease (PD) is the second most common neurodegenerative disease in humans. The hormone alpha-melanocyte-stimulating hormone (alpha-MSH) has been reported to be neuroprotective in previous studies. The aim of this study is to investigate the neuroprotective effects of alpha-MSH against the neurotoxicity of 1-methyl-4-phenylpyridinium (MPP+). Our results indicated that treatment with alpha-MSH in M17 cells attenuated MPP+-induced oxidative stress, embodied by exacerbated reactive oxygen species and protein carbonyls. In addition, we found that alpha-MSH could improve mitochondrial function in M17 cells through increasing the level of adenosine triphosphate and mitochondrial membrane potential. Furthermore, treatment with alpha-MSH restored the reduction of cell viability and the induction of lactate dehydrogenase release induced by alpha MSH. Importantly, Hoechst staining results indicated that alpha-MSH treatment significantly reduces the number of apoptotic cells after treatment with MPP+. Mechanically, we found that alpha-MSH prevented apoptosis signals through reducing the level of cleaved caspase-3 and attenuating cytochrome c release. All these data imply that alpha-MSH produces a protective effect in PD. (c) 2015 IUBMB Life, 69(5):315-320, 2017. PMID- 26136378 TI - Bisamidate Prodrugs of 2-Substituted 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA, adefovir) as Selective Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis. AB - Novel small-molecule agents to treat Bordetella pertussis infections are highly desirable, as pertussis (whooping cough) remains a serious health threat worldwide. In this study, a series of 2-substituted derivatives of 9-[2 (phosphonomethoxy)ethyl]adenine (PMEA, adefovir), in their isopropyl ester bis(L phenylalanine) prodrug form, were designed and synthesized as potent inhibitors of adenylate cyclase toxin (ACT) isolated from B. pertussis. The series consists of PMEA analogues bearing either a linear or branched aliphatic chain or a heteroatom at the C2 position of the purine moiety. Compounds with a small C2 substituent showed high potency against ACT without cytotoxic effects as well as good selectivity over human adenylate cyclase isoforms AC1, AC2, and AC5. The most potent ACT inhibitor was found to be the bisamidate prodrug of the 2-fluoro PMEA derivative (IC50 =0.145 MUM). Although the bisamidate prodrugs reported herein exhibit overall lower activity than the bis(pivaloyloxymethyl) prodrug (adefovir dipivoxil), their toxicity and plasma stability profiles are superior. Furthermore, the bisamidate prodrug was shown to be more stable in plasma than in macrophage homogenate, indicating that the free phosphonate can be effectively distributed to target tissues, such as the lungs. Thus, ACT inhibitors based on acyclic nucleoside phosphonates may represent a new strategy to treat whooping cough. PMID- 26136380 TI - Distinct mechanistic differences in the hydrogen-atom transfer from methane and water by the heteronuclear oxide cluster [Ga2 MgO4](.). AB - The thermal reactions of the heteronuclear oxide cluster [Ga2 MgO4 ](.+) with methane and water have been studied using state-of-the-art gas-phase experiments in conjunction with quantum-chemical calculations. The significant reactivity differences, favoring activation of the strong O?H bond, can be ascribed to a proton-coupled electron transfer (PCET) mechanism operative in the activation of water. This study deepens our mechanistic understanding on how inert R?H bonds are cleaved by metal oxides. PMID- 26136379 TI - Net aboveground biomass declines of four major forest types with forest ageing and climate change in western Canada's boreal forests. AB - Biomass change of the world's forests is critical to the global carbon cycle. Despite storing nearly half of global forest carbon, the boreal biome of diverse forest types and ages is a poorly understood component of the carbon cycle. Using data from 871 permanent plots in the western boreal forest of Canada, we examined net annual aboveground biomass change (DeltaAGB) of four major forest types between 1958 and 2011. We found that DeltaAGB was higher for deciduous broadleaf (DEC) (1.44 Mg ha(-1) year(-1) , 95% Bayesian confidence interval (CI), 1.22 1.68) and early-successional coniferous forests (ESC) (1.42, CI, 1.30-1.56) than mixed forests (MIX) (0.80, CI, 0.50-1.11) and late-successional coniferous (LSC) forests (0.62, CI, 0.39-0.88). DeltaAGB declined with forest age as well as calendar year. After accounting for the effects of forest age, DeltaAGB declined by 0.035, 0.021, 0.032 and 0.069 Mg ha(-1) year(-1) per calendar year in DEC, ESC, MIX and LSC forests, respectively. The DeltaAGB declines resulted from increased tree mortality and reduced growth in all forest types except DEC, in which a large biomass loss from mortality was accompanied with a small increase in growth. With every degree of annual temperature increase, DeltaAGB decreased by 1.00, 0.20, 0.55 and 1.07 Mg ha(-1) year(-1) in DEC, ESC, MIX and LSC forests, respectively. With every cm decrease of annual climatic moisture availability, DeltaAGB decreased 0.030, 0.045 and 0.17 Mg ha(-1) year(-1) in ESC, MIX and LSC forests, but changed little in DEC forests. Our results suggest that persistent warming and decreasing water availability have profound negative effects on forest biomass in the boreal forests of western Canada. Furthermore, our results indicate that forest responses to climate change are strongly dependent on forest composition with late-successional coniferous forests being most vulnerable to climate changes in terms of aboveground biomass. PMID- 26136382 TI - Development of a new procedure for the determination of captopril in pharmaceutical formulations employing chemiluminescence and a multicommuted flow analysis approach. AB - This paper describes a new technique for the determination of captopril in pharmaceutical formulations, implemented by employing multicommuted flow analysis. The analytical procedure was based on the reaction between hypochlorite and captopril. The remaining hypochlorite oxidized luminol that generated electromagnetic radiation detected using a homemade luminometer. To the best of our knowledge, this is the first time that this reaction has been exploited for the determination of captopril in pharmaceutical products, offering a clean analytical procedure with minimal reagent usage. The effectiveness of the proposed procedure was confirmed by analyzing a set of pharmaceutical formulations. Application of the paired t-test showed that there was no significant difference between the data sets at a 95% confidence level. The useful features of the new analytical procedure included a linear response for captopril concentrations in the range 20.0-150.0 umol/L (r = 0.997), a limit of detection (3sigma) of 2.0 umol/L, a sample throughput of 164 determinations per hour, reagent consumption of 9 ug luminol and 42 ug hypochlorite per determination and generation of 0.63 mL of waste. A relative standard deviation of 1% (n = 6) for a standard solution containing 80 umol/L captopril was also obtained. PMID- 26136381 TI - Molecular cloning and characterization of oocyte-specific Pat1a in Rana rugosa frogs. AB - The Pat1 gene is expressed in the immature oocytes of Xenopus, and is reportedly involved in regulating the translation of maternal mRNAs required for oocyte maturation. However, it is still unknown when Pat1a first appears in the differentiating ovary of amphibians. To address this issue, we isolated the full length Pat1a cDNA from the frog Rana rugosa and examined its expression in the differentiating ovary of this frog. Among eight different tissues examined, the Pat1a mRNA was detectable in only the ovary. When frozen sections from the ovaries of tadpoles at various stages of development were immunostained for Vasa a germ cell-specific protein-and Pat1a, Vasa-immunopositive signals were observed in all of the germ cells, whereas Pat1a signals were confined to the growing oocytes (50-200 MUm in diameter), and absent from small germ cells (<50 MUm in diameter). Forty days after testosterone injection into tadpoles to induce female to-male sex-reversal, Pat1a-immunoreactive oocytes had disappeared completely from the sex-reversed gonad, but Vasa-positive small germ cells persisted. Thus, Pat1a would be a good marker for identifying the sexual status of the sex reversing gonad in amphibians. In addition, fluorescence in situ hybridization analysis showed Pat1a to have an autosomal locus, suggesting that Pat1a transcription is probably regulated by a tissue-specific transcription factor in R. rugosa. PMID- 26136383 TI - 60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly. AB - Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population. PMID- 26136384 TI - Adrenocortical LDL receptor function negatively influences glucocorticoid output. AB - Over 50% of the cholesterol needed by adrenocortical cells for the production of glucocorticoids is derived from lipoproteins. However, the overall contribution of the different lipoproteins and associated uptake pathways to steroidogenesis remains to be determined. Here we aimed to show the importance of LDL receptor (LDLR)-mediated cholesterol acquisition for adrenal steroidogenesis in vivo. Female total body LDLR knockout mice with a human-like lipoprotein profile were bilaterally adrenalectomized and subsequently provided with one adrenal either expressing or genetically lacking the LDLR under their renal capsule to solely modulate adrenocortical LDLR function. Plasma total cholesterol levels and basal plasma corticosterone levels were identical in the two types of adrenal transplanted mice. Strikingly, restoration of adrenal LDLR function significantly reduced the ACTH-mediated stimulation of adrenal steroidogenesis (P<0.001), with plasma corticosterone levels that were respectively 44-59% lower (P<0.01) as compared to adrenal LDLR negative controls. In addition, LDLR positive adrenal transplanted mice exhibited a significant decrease (-39%; P<0.001) in their plasma corticosterone level under fasting stress conditions. Biochemical analysis did not show changes in the expression of genes involved in cholesterol mobilization. However, LDLR expressing adrenal transplants displayed a marked 62% reduction (P<0.05) in the transcript level of the key steroidogenic enzyme HSD3B2. In conclusion, our studies in a mouse model with a human-like lipoprotein profile provide the first in vivo evidence for a novel inhibitory role of the LDLR in the control of adrenal glucocorticoid production. PMID- 26136386 TI - Thromboembolic risk stratification of patients hospitalized with heart failure in sinus rhythm: a nationwide cohort study. AB - AIMS: Patients with heart failure in sinus rhythm are at an increased risk of thromboembolic complications. So far, validated risk stratification tools are lacking for such patients, which makes the decision to initiate anti-thrombotic treatment difficult. METHODS AND RESULTS: We included 136,545 patients admitted with heart failure in sinus rhythm from national registries from 1999 to 2012. Patients receiving oral anticoagulants were omitted from the study. First, we investigated if the CHA2DS2-VASc score could identify heart failure patients in sinus rhythm with high rates of thromboembolic complications. Second, we investigated if any single CHA2DS2-VASc risk factor carried a greater prognostic value with regard to thromboembolism. The risk of thromboembolism increased more than ninefold (hazard ratio 9.2, 95% confidence interval 6.8-12.5) in patients with all CHA2DS2-VASc risk factors compared with those with heart failure alone. The incidence rates of thromboembolism were clinically significant, averaging 6.0 (95% confidence interval 5.98-6.02) events per 100 patient years during the first year following diagnosis. Risk factors such as diabetes, age, vascular disease, and especially previous thromboembolism, conferred an independent risk of future thromboembolism. CONCLUSION: The CHA2DS2-VASc risk stratification scheme was able to provide prognostic information on future thromboembolic events in patients with heart failure in sinus rhythm. The CHA2DS2-VASc scale could be easily implemented as an aid to clinicians in risk stratifying heart failure patients in sinus rhythm, for thromboembolism. PMID- 26136387 TI - Mercury under Pressure acts as a Transition Metal: Calculated from First Principles. AB - The inclusion of Hg among the transition metals is readily debated. Recently, molecular HgF4 was synthesized in a low-temperature noble gas but the potential of Hg to form compounds beyond a +2 oxidation state in a stable solid remains unresolved. We propose high-pressure techniques to prepare unusual oxidation states of Hg-based compounds. Using an advanced structure search algorithm and first-principles electronic structure calculations, we find that under high pressure Hg in Hg-F compounds transfers charge from the d orbitals to the F, thus behaving as a transition metal. Oxidizing Hg to +4 and +3 yielded the thermodynamically stable compounds HgF4 and HgF3. The former consists of HgF4 planar molecules, a typical geometry for d(8) metal centers. HgF3 is metallic and ferromagnetic owing to the d(9) configuration of Hg, with a large gap between its partially occupied and unoccupied bands under high pressure. PMID- 26136385 TI - Therapeutic Developments Targeting Toll-like Receptor-4-Mediated Neuroinflammation. AB - Toll-like receptors (TLRs) have been shown to play an important role in the immune system, which warrants study of their remarkable potential as pharmacological targets. Activation of TLRs requires participation from specific pathogen-associated molecular patterns (PAMPs) and accessory proteins such as myeloid differentiation protein 2 (MD2), lipopolysaccharide binding protein (LBP), and cluster differentiation antigen 14 (CD14). Assembly of the TLR4-MD2 LPS complex is essential in TLR4 activation. Recent studies have revealed that TLR4 activation is a significant trigger of signal transmission pathways in the nervous system, which could result in chronic pain as well as opioid tolerance and dependence. Researchers of the molecular structure of TLRs and their accessory proteins have opened a door to syntheses of TLRs agonists and antagonists, such as eritoran. Small-molecule modulators of TLR4, such as MD2-I and tricyclic antidepressants, offer more promising prospects than peptides, given their convenience in oral administration and lower cost. Herein we mainly discuss the mechanisms and clinical prospects of TLR4 agonists and antagonists. PMID- 26136388 TI - Morphometric Study of the Mare Oviductal Mucosa at Different Reproductive Stages. AB - The objectives of this work were to describe some morphometric characteristics and to establish quantitative parameters of different regions of the equine oviductal mucosa from the isthmus, ampullary-isthmic junction (AIJ), and ampulla. Twenty-one mixed-bred mares were used for this study. Mares were selected in the following reproductive phases: anestrus, estrus, and diestrus. The left oviducts were examined with light microscopy, and rights ones were studied through the intraoviductal molds. The isthmus showed the smallest luminal area, mucosal area, epithelial perimeter, and luminal diameter. On the molds surfaces, some grooves extended as longitudinal canals, reducing their depth as they approached to the AIJ. Several small height projections, some obliquely positioned towards utero tubal junction, were observed in all reproductive phases. These formations may represent pockets or cul-de-sacs in the basal areas of the epithelial folds. The AIJ mucosa gradually changed from the smooth isthmic region toward highly folded ampulla. The number and complexity of epithelial folds showed moderate increase in the same way that many of the morphometric parameters. Multiple curves were observed on the molds of the AIJ, creating a zigzag path in the oviductal lumen. In the ampulla, the high branched epithelial folds occupied most of the lumen, leaving a small luminal area free. A linear relationship between epithelial perimeter and mucosal area was found. The presence of glandular-like structures was observed in all the reproductive stages studied. The equine endosalpinx reveals a highly complex tridimensional arrangement where each region shows very particular and specific designs. PMID- 26136389 TI - Prosthetic Endocarditis Caused by Streptococcus bovis Group. PMID- 26136390 TI - Hepatitis C Management and the Infectious Diseases Pharmacist. PMID- 26136392 TI - Editorial Commentary: Toward a Better Malaria Vaccine: Understanding How Antibodies to Malaria Protect Against Disease. PMID- 26136391 TI - Acquisition of Functional Antibodies That Block the Binding of Erythrocyte Binding Antigen 175 and Protection Against Plasmodium falciparum Malaria in Children. AB - BACKGROUND: The targets and mechanisms of human immunity to malaria are poorly understood, which poses a major barrier to malaria vaccine development. Antibodies play a key role in human immunity and may act by inhibiting receptor binding functions of key merozoite invasion ligands. Antibodies to the major invasion ligand and vaccine candidate, erythrocyte-binding antigen 175 (EBA-175), have been linked with protection, but how these antibodies function has not been established. METHODS: We developed 2 new assays that quantify the ability of antibodies to inhibit binding of EBA-175 to its erythrocyte receptor, glycophorin A, using either native or recombinant EBA-175. Binding-inhibitory antibodies were evaluated in a longitudinal cohort study of Papua New Guinean children and related to risk of malaria, age, infection status, and markers of parasite exposure. RESULTS: Binding-inhibition assays (BIAs) were reproducible, and the 2 assays had a high level of agreement. Inhibitory antibodies were common among children, acquired in association with markers of increasing parasite exposure, and high in those children with active infection. Inhibitory antibodies correlated with total immunoglobulin G levels to the EBA-175 binding domain (region II). Importantly, binding-inhibitory antibodies were significantly associated with protection from symptomatic malaria when measured using either BIA. CONCLUSIONS: Findings suggest that naturally acquired binding-inhibitory antibodies are an important functional mechanism that contributes to protection against malaria and further supports the potential of EBA-175 as a vaccine candidate. Identifying vaccines and approaches that induce potent binding inhibitory antibodies may be a valuable strategy in the development of highly efficacious malaria vaccines. PMID- 26136393 TI - Long-term Efficacy of Dental Implants in HIV-Positive Patients. PMID- 26136395 TI - Integrative biomarker discovery in neurodegenerative diseases. AB - Data mining has been widely applied in biomarker discovery resulting in significant findings of different clinical and biological biomarkers. With developments in technology, from genomics to proteomics analysis, a deluge of data has become available, as well as standardized data repositories. Nonetheless, researchers are still facing important challenges in analyzing the data, especially when considering the complexity of pathways involved in biological processes and diseases. Data from single sources appear unable to explain complex processes, such as those involved in brain-related disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, thus raising the need for a more comprehensive perspective. A possible solution relies on data and model integration, where several data types are combined to provide complementary views. This in turn can result in the discovery of previously unknown biomarkers by unraveling otherwise hidden relationships between data from different sources, and/or validate such composite biomarkers in more powerful predictive models. PMID- 26136396 TI - Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR. AB - Opportunistic pathogens exploit diverse strategies to sabotage host defenses. Pseudomonas aeruginosa secretes the CFTR inhibitory factor Cif and thus triggers loss of CFTR, an ion channel required for airway mucociliary defense. However, the mechanism of action of Cif has remained unclear. It catalyzes epoxide hydrolysis, but there is no known role for natural epoxides in CFTR regulation. It was demonstrated that the hydrolase activity of Cif is strictly required for its effects on CFTR. A small-molecule inhibitor that protects this key component of the mucociliary defense system was also uncovered. These results provide a basis for targeting the distinctive virulence chemistry of Cif and suggest an unanticipated role of physiological epoxides in intracellular protein trafficking. PMID- 26136397 TI - Risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients. AB - Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is increasing in incidence and is associated with increased mortality in liver transplantation (LT) recipients. We performed a retrospective cohort study of all patients transplanted between January 2010 and January 2013 to identify the incidence and risk factors for post-LT CRKP infection and evaluate the impact of this infection on outcomes in a CRKP-endemic area. We studied 304 recipients, of whom 20 (6.6%) developed CRKP and 36 (11.8%) carbapenem-susceptible Klebsiella pneumoniae (CSKP) infections in the year following LT. Among the 20 recipients with post-LT CRKP infection, 8 (40%) were infected in >= 2 sites; 13 (65%) had surgical site-intra abdominal infections; 12 (60%) had pneumonia; and 3 (15%) had a urinary tract infection. There were 6 patients with a CRKP infection before LT, 5 of whom developed a CRKP infection after LT. Significant risk factors for post-LT CRKP infection in multivariate analysis included laboratory Model for End-Stage Liver Disease at LT (odds ratio [OR], 1.07; P = 0.001), hepatocellular carcinoma (OR, 3.19; P = 0.02), Roux-en-Y biliary choledochojejunostomy (OR, 3.15; P = 0.04), and bile leak (OR, 5.89; P = 0.001). One-year estimated patient survival was 55% (95% confidence interval, 31%-73%), 72% (55%-84%), and 93% (89%-96%), for patients with CRKP, CSKP, and no Klebsiella pneumoniae infection, respectively. In multivariate analysis, CRKP (hazard ratio [HR], 6.92; P < 0.001) and CSKP infections (CSKP, HR, 3.84; P < 0.001), as well as bile leak (HR, 2.10; P = 0.03) were the strongest predictors of post-LT mortality. In an endemic area, post-LT CRKP infection is common, occurring in 6.6% of recipients, and is strongly associated with post-LT mortality. Improved strategies for screening and prevention of CRKP infection are urgently needed. PMID- 26136398 TI - On the Role of Metals in Nitrogen-Doped Carbon Electrocatalysts for Oxygen Reduction. AB - The notion of metal-free catalysts is used to refer to carbon materials modified with nonmetallic elements. However, some claimed metal-free catalysts are prepared using metal-containing precursors. It is highly contested that metal residues in nitrogen-doped carbon (NC) catalysts play a crucial role in the oxygen reduction reaction (ORR). In an attempt to reconcile divergent views, a definition for truly metal-free catalysts is proposed and the differences between NC and M-Nx /C catalysts are discussed. Metal impurities at levels usually undetectable by techniques such as XPS, XRD, and EDX significantly promote the ORR. Poisoning tests to mask the metal ions reveal the involvement of metal residues as active sites or as modifiers of the electronic structure of the active sites in NC. The unique merits of both M-Nx /C and NC catalysts are discussed to inspire the development of more advanced nonprecious-metal catalysts for the ORR. PMID- 26136394 TI - Facing and Overcoming Sensitivity Challenges in Biomolecular NMR Spectroscopy. AB - In the Spring of 2013, NMR spectroscopists convened at the Weizmann Institute in Israel to brainstorm on approaches to improve the sensitivity of NMR experiments, particularly when applied in biomolecular settings. This multi-author interdisciplinary Review presents a state-of-the-art description of the primary approaches that were considered. Topics discussed included the future of ultrahigh-field NMR systems, emerging NMR detection technologies, new approaches to nuclear hyperpolarization, and progress in sample preparation. All of these are orthogonal efforts, whose gains could multiply and thereby enhance the sensitivity of solid- and liquid-state experiments. While substantial advances have been made in all these areas, numerous challenges remain in the quest of endowing NMR spectroscopy with the sensitivity that has characterized forms of spectroscopies based on electrical or optical measurements. These challenges, and the ways by which scientists and engineers are striving to solve them, are also addressed. PMID- 26136399 TI - Measurement of ciliary beat frequency using Doppler optical coherence tomography. AB - BACKGROUND: Measuring ciliary beat frequency (CBF) is a technical challenge and difficult to perform in vivo. Doppler optical coherence tomography (D-OCT) is a mesoscopic noncontact imaging modality that provides high-resolution tomographic images and detects micromotion simultaneously in living tissues. In this work we used D-OCT to measure CBF in ex vivo tissue as the first step toward translating this technology to clinical use. METHODS: Fresh ex vivo samples of rabbit tracheal mucosa were imaged using both D-OCT and phase-contrast microscopy (n = 5). The D-OCT system was designed and built to specification in our lab (1310-nm swept source vertical-cavity surface-emitting laser [VCSEL], 6-MUm axial resolution). The samples were placed in culture and incubated at 37 degrees C. A fast Fourier transform was performed on the D-OCT signal recorded on the surface of the samples to gauge CBF. High-speed digital video of the epithelium recorded via phase-contrast microscopy was analyzed to confirm the CBF measurements. RESULTS: The D-OCT system detected Doppler signal at the epithelial layer of ex vivo rabbit tracheal samples suggestive of ciliary motion. CBF was measured at 9.36 +/- 1.22 Hz using D-OCT and 9.08 +/- 0.48 Hz using phase-contrast microscopy. No significant differences were found between the 2 methods (p > 0.05). CONCLUSION: D-OCT allows for the quantitative measurement of CBF without the need to resolve individual cilia. Furthermore, D-OCT technology can be incorporated into endoscopic platforms that allow clinicians to readily measure CBF in the office and provide a direct measurement of mucosal health. PMID- 26136400 TI - Beneficial Effect on Cardiac Resynchronization From Left Ventricular Endocardial Pacing Is Mediated by Early Access to High Conduction Velocity Tissue: Electrophysiological Simulation Study. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) delivered via left ventricular (LV) endocardial pacing (ENDO-CRT) is associated with improved acute hemodynamic response compared with LV epicardial pacing (EPI-CRT). The role of cardiac anatomy and physiology in this improved response remains controversial. We used computational electrophysiological models to quantify the role of cardiac geometry, tissue anisotropy, and the presence of fast endocardial conduction on myocardial activation during ENDO-CRT and EPI-CRT. METHODS AND RESULTS: Cardiac activation was simulated using the monodomain tissue excitation model in 2 dimensional (2D) canine and human and 3D canine biventricular models. The latest activation times (LATs) for LV endocardial and biventricular epicardial tissue were calculated (LVLAT and TLAT), as well the percentage decrease in LATs for endocardial (en) versus epicardial (ep) LV pacing (defined as %dLV=100*(LVLATep LVLATen)/LVLATep and %dT=100*(TLATep-TLATen)/TLATep, respectively). Normal canine cardiac anatomy is responsible for %dLV and %dT values of 7.4% and 5.5%, respectively. Concentric and eccentric remodeled anatomies resulted in %dT values of 15.6% and 1.3%, respectively. The 3D biventricular-paced canine model resulted in %dLV and %dT values of -7.1% and 1.5%, in contrast to the experimental observations of 16% and 11%, respectively. Adding fast endocardial conduction to this model altered %dLV and %dT to 13.1% and 10.1%, respectively. CONCLUSIONS: Our results provide a physiological explanation for improved response to ENDO CRT. We predict that patients with viable fast-conducting endocardial tissue or distal Purkinje network or both, as well as concentric remodeling, are more likely to benefit from reduced ATs and increased synchrony arising from endocardial pacing. PMID- 26136401 TI - Liver transplantation for alcoholic hepatitis: A survey of liver transplant centers. PMID- 26136402 TI - alpha-Peptide-Oligourea Chimeras: Stabilization of Short alpha-Helices by Non Peptide Helical Foldamers. AB - Short alpha-peptides with less than 10 residues generally display a low propensity to nucleate stable helical conformations. While various strategies to stabilize peptide helices have been previously reported, the ability of non peptide helical foldamers to stabilize alpha-helices when fused to short alpha peptide segments has not been investigated. Towards this end, structural investigations into a series of chimeric oligomers obtained by joining aliphatic oligoureas to the C- or N-termini of alpha-peptides are described. All chimeras were found to be fully helical, with as few as 2 (or 3) urea units sufficient to propagate an alpha-helical conformation in the fused peptide segment. The remarkable compatibility of alpha-peptides with oligoureas described here, along with the simplicity of the approach, highlights the potential of interfacing natural and non-peptide backbones as a means to further control the behavior of alpha-peptides. PMID- 26136403 TI - Demographic patterns of cutaneous T-cell lymphoma incidence in Texas based on two different cancer registries. AB - Cutaneous T-cell lymohomas (CTCLs) are rare, but potentially devastating malignancies, with Mycosis fungoides and Sezary Syndrome being the most common. In our previous study, we identified and described regions of geographic clustering of CTCL cases in Texas by analyzing ~1990 patients using two distinct cancer registries. In the current work, we describe in detail demographic patterns for this malignancy in our study population and apply logistic regression models to analyze the incidence of CTCL by sex, race, age, and clinical stage at the time of diagnosis. Furthermore, using Fisher's exact test, we analyze changes in incidence over time in the identified Houston communities with unusually high CTCL incidence. While CTCL primarily affects Caucasian individuals >55 years old, we confirm that it presents at a younger age and with more advanced disease stages in African-American and Hispanic individuals. Also, we demonstrate a significant increase in CTCL incidence over time in the identified communities. Spring, Katy, and Houston Memorial areas had high baseline rates. Furthermore, a statistically significant disease surge was observed in these areas after ~2005. This report supplements our initial study documenting the existence of geographic clustering of CTCL cases in Texas and in greater detail describes demographic trends for our patient population. The observed surge in CTCL incidence in the three identified communities further argues that this malignancy may be triggered by one or more external etiologic agents. PMID- 26136404 TI - Lessons Learned From a Randomized Controlled Trial of a Family-Based Intervention to Promote School Functioning for School-Age Children With Sickle Cell Disease. AB - OBJECTIVE: Tested a family-based group problem-solving intervention, "Families Taking Control," (FTC) to improve school functioning and health-related quality of life (HRQL) for children with sickle cell disease. METHOD: Children and caregivers completed questionnaires assessing HRQL and school functioning and children completed performance-based measures of IQ and achievement at baseline and 6 months later. Families were randomized to the intervention (FTC, n = 42) or delayed intervention control (DIC, n = 41) group. FTC involved a full-day workshop followed by 3 booster calls. RESULTS: There were no differences between FTC completers (n = 24) and noncompleters (n = 18). FTC group (n = 24) and DIC group (n = 38) did not differ significantly on primary outcomes at follow-up: number of formal academic and disease-related accommodations, individualized education plan/504 service plan, school absences, school HRQL, or academic skills. CONCLUSIONS: Although families found FTC to be acceptable, there were no intervention effects. Challenges of the trial and implications for future research are discussed. PMID- 26136406 TI - Transition-Metal-Free alpha-Arylation of Enolizable Aryl Ketones and Mechanistic Evidence for a Radical Process. AB - The alpha-arylation of enolizable aryl ketones can be carried out with aryl halides under transition-metal-free conditions using KOtBu in DMF. The alpha-aryl ketones thus obtained can be used for step- and cost-economic syntheses of fused heterocycles and Tamoxifen. Mechanistic studies demonstrate the synergetic role of base and solvent for the initiation of the radical process. PMID- 26136405 TI - Secrecy From Parents and Type 1 Diabetes Management in Late Adolescence. AB - OBJECTIVES: This study examined (a) associations of parent-adolescent relationship characteristics and adolescent problem behavior with late adolescents' secrecy from parents about type 1 diabetes management, and (b) whether secrecy was associated with diabetes and psychological outcomes independently of these factors. METHODS: Adolescents (N = 247, Mage = 17.76 years) completed survey measures of diabetes-related secrecy from parents, disclosure, parental acceptance, parental knowledge, and conduct problems. Mothers and adolescents reported on adolescent adherence to diabetes regimens and adolescents reported their depressive symptoms. Glycemic control was obtained from HbA1c test kits. RESULTS: Adolescent-reported disclosure to parents was uniquely negatively associated with secrecy from parents. Controlling for relationship variables, conduct problems, and sociodemographic and illness related variables, secrecy from mothers was uniquely associated with poorer glycemic control and secrecy from both parents was associated with lower adherence. CONCLUSIONS: Secrecy about type 1 diabetes management is uniquely associated with diabetes outcomes independent of other relationship characteristics and problem behaviors. PMID- 26136408 TI - More colour to the Journal: new style, new publisher, but still Cachexia, Sarcopenia and Muscle. PMID- 26136407 TI - Optimal management of cervical cancer in HIV-positive patients: a systematic review. AB - The clinical management of cervical cancer in HIV-positive patients has challenges mainly due to the concerns on immune status. At present, their mode of management is similar to HIV-seronegative patients involving the use of chemotherapy and radiotherapy concurrently as indicated. HIV infection, cancer, radiotherapy, and chemotherapy lower immunity through reduction in CD4 cell counts. At present there are no treatment guidelines for HIV-positive patients. This study was done to systematically review the literature on cervical cancer management in HIV-positive patients and treatment outcomes. A systematic literature search was done in the major databases to identify studies on the management of HIV-positive patients with cervical cancer. Identified studies were assessed for eligibility and inclusion in the review following the guidelines of The Cochrane Handbook for Systematic Reviews and CRD's (Centre for Reviews and Dissemination) guidance for undertaking reviews in health care. Eight eligible studies were identified from the literature. Three of them were prospective while five were retrospective studies. Notably, the average age at diagnosis of cervical cancer in HIV-positive patients was a decade lower than in seronegative patients. There was no difference in distribution of stages of disease at presentation between HIV-positive and negative patients. Mild acute toxicity (Grades 1 and 2) was higher in HIV-positive patients than in HIV-negative patients in hematopoietic system. In the grades 3 and 4 reactions, anemia was reported in 4% versus 2% while gastrointestinal reactions were reported in 5% versus 2% respectively. In general, patients who were started early on HAART had higher rates of treatment completion. The study supports the suggestion that HAART should be commenced early at cervical cancer diagnosis in HIV-positive patients diagnosed with cervical cancer to ensure less toxicity and better treatment compliance. PMID- 26136409 TI - Abstracts of the 2(nd) Cancer Cachexia Conference, Montreal, Canada, 26-28 September 2014. PMID- 26136410 TI - Improved body weight and performance status and reduced serum PGE2 levels after nutritional intervention with a specific medical food in newly diagnosed patients with esophageal cancer or adenocarcinoma of the gastro-esophageal junction. AB - BACKGROUND: The majority of cancer patients loses weight and becomes malnourished during the course of their disease. Metabolic alterations and reduced immune competence lead to wasting and an increased risk of infectious complications. In the present study, the effect of a nutritionally complete medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides, was investigated on immune function, nutritional status, and inflammation in patients with esophageal cancer and compared with routine care. METHODS: In this exploratory double-blind study, 64 newly diagnosed esophageal cancer patients were randomized. All patients received dietary counselling and dietary advice. In the Active group, all patients received the specific medical food for 4 weeks before the start of anticancer therapy. In the routine care control arm, patients with <5% weight loss received a non-caloric placebo product, and patients with weight loss >=5% received an iso-caloric control product to secure blinding of the study. The required study parameters of body weight and performance status were recorded at baseline and after 4 weeks of nutritional intervention, and patients were asked to complete quality of life questionnaires. In addition, blood samples were taken for the measurement of several immune, nutritional, and safety-parameters. RESULTS: No effect of the specific nutritional intervention could be detected on ex vivo stimulations of blood mononuclear cells. By contrast, body weight was significantly increased (P < 0.05) and ECOG performance status was improved after intervention with the specific medical food (P < 0.05). In addition, serum Prostaglandin E2 (PGE2) levels were significantly decreased in the specific medical food group and increased in the control group (P = 0.002). CONCLUSIONS: Nutritional intervention with the specific medical food significantly increased body weight and improved performance status compared with routine care in newly diagnosed esophageal cancer patients. This effect was accompanied by significantly reduced serum PGE2 levels. PMID- 26136411 TI - Influence of cancer cachexia on drug liver metabolism and renal elimination in rats. AB - BACKGROUND: Body wasting and cachexia change body composition and organ function, with effects on drug pharmacokinetics. The aim of this study was to investigate how cancer and cancer cachexia modify liver metabolism and renal drug elimination in rats. METHODS: Nine male Wistar-Han rats received a single oral dose of midazolam and propranolol (markers of hepatic metabolism), and 10 rats received single intravenous dose of iohexol, a marker of glomerular filtration rate. After drug delivery, multiple dried blood samples were obtained within 2 h post-dose to evaluate drug pharmacokinetic profiles. After baseline sampling (D0), rats were injected with tumour cells. Drug application and blood sampling were repeated when rats developed tumours (Day 5-D5), and when rats were severely cachectic (Day 10-D10). Clearance (CL) and volume of distribution (Vd) of drugs were assessed with non-linear mixed effects modelling. Weight and body composition were measured on D0 and D10 and were related to pharmacokinetic parameters. RESULTS: All three drugs showed non-significant trend towards increased CL and Vd on D5. On D10, midazolam and propranolol CL and midazolam Vd significantly decreased from baseline (-80.5%, -79.8%, and -72.0%, respectively, P < 0.05 for all). Iohexol CL decreased by 29.8% from baseline value on D10, which was related to body weight loss (Pearson's r = 0.837, P = 0.019). CONCLUSIONS: Hepatic metabolism and renal drug elimination are significantly reduced in cachexia, which could increase risk of dose-related adverse events. PMID- 26136412 TI - Evaluating potential biomarkers of cachexia and survival in skeletal muscle of upper gastrointestinal cancer patients. AB - BACKGROUND: In order to grow the potential therapeutic armamentarium in the cachexia domain of supportive oncology, there is a pressing need to develop suitable biomarkers and potential drug targets. This pilot study evaluated several potential candidate biomarkers in skeletal muscle biopsies from a cohort of upper gastrointestinal cancer (UGIC) patients. METHODS: One hundred seven patients (15 weight-stable healthy controls (HC) and 92 UGIC patients) were recruited. Mean (standard deviation) weight-loss of UGIC patients was 8.1 (9.3%). Cachexia was defined as weight-loss >=5%. Rectus abdominis muscle was obtained at surgery and was analysed by western blotting or quantitative real-time-polymerase chain reaction. Candidate markers were selected according to previous literature and included Akt and phosphorylated Akt (pAkt, n = 52), forkhead box O transcription factors (n = 59), ubiquitin E3 ligases (n = 59, control of muscle anabolism/catabolism), BNIP3 and GABARAPL1 (n = 59, as markers of autophagy), myosin heavy-chain (MyHC, n = 54), dystrophin (n = 39), beta-dystroglycan (n = 52), and beta-sarcoglycan (n = 52, as markers of structural alteration in a muscle). Patients were followed up for an average of 1255 days (range 581-1955 days) or until death. Patients were grouped accordingly and analysed by (i) all cancer patients vs. HC; (ii) cachectic vs. non-cachectic cancer patients; and (iii) cancer patients surviving <=1 vs. >1 year post operatively. RESULTS: Cancer compared with HC patients had reduced mean (standard deviation) total Akt protein [0.49 (0.31) vs. 0.89 (0.17), P = 0.001], increased ratio of phosphorylated to total Akt [1.33 (1.04) vs. 0.32 (0.21), P = 0.002] and increased expression of GABARAPL1 [1.60 (0.76) vs. 1.10 (0.57), P = 0.024]. beta-Dystroglycan levels were higher in cachectic compared with non-cachectic cancer patients [1.01 (0.16) vs. 0.87 (0.20), P = 0.007]. Survival was shortened in patients with low compared with high MyHC levels (median 316 vs. 1326 days, P = 0.023) and dystrophin levels (median 341 vs. 660 days, P = 0.008). CONCLUSIONS: The present study has identified intramuscular protein level of beta-dystroglycan as a potential biomarker of cancer cachexia. Changes in the structural elements of muscle (MyHC or dystrophin) appear to be survival biomarkers. PMID- 26136413 TI - Fibronectin type III domain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines. AB - BACKGROUND: Chronic heart failure (CHF) is commonly associated with muscle atrophy and increased inflammation. Irisin, a myokine proteolytically processed by the fibronectin type III domain containing 5 (FNDC5) gene and suggested to be Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha activated, modulates the browning of adipocytes and is related to muscle mass. Therefore, we investigated whether skeletal muscle FNDC5 expression in CHF was reduced and if this was mediated by inflammatory cytokines and/or angiotensin II (Ang-II). METHODS: Skeletal muscle FNDC5 mRNA/protein and PGC-1alpha mRNA expression (arbitrary units) were analysed in: (i) rats with ischemic cardiomyopathy; (ii) mice injected with tumour necrosis factor-alpha (TNF-alpha) (24 h); (iii) mice infused with Ang-II (4 weeks); and (iv) C2C12 myotubes exposed to recombinant cytokines or Ang-II. Circulating TNF-alpha, Ang-II, and irisin was measured by ELISA. RESULTS: Ischemic cardiomyopathy reduced significantly FNDC5 protein (1.3 +/- 0.2 vs. 0.5 +/- 0.1) and PGC-1alpha mRNA expression (8.2 +/- 1.5 vs. 4.7 +/- 0.7). In vivo TNF-alpha and Ang-II reduced FNDC5 protein expression by 28% and 45%, respectively. Incubation of myotubes with TNF-alpha, interleukin 1beta, or TNF-alpha/interleukin-1beta reduced FNDC5 protein expression by 47%, 37%, or 57%, respectively, whereas Ang-II had no effect. PGC-1alpha was linearly correlated to FNDC5 in all conditions. In CHF, animals circulating TNF-alpha and Ang-II were significantly increased, whereas irisin was significantly reduced. A negative correlation between circulating TNF-alpha and irisin was evident. CONCLUSION: A reduced expression of skeletal muscle FNDC5 in ischemic cardiomyopathy is likely modulated by inflammatory cytokines and/or Ang-II via the down-regulation of PGC-1alpha. This may act as a protective mechanism either by slowing the browning of adipocytes and preserving energy homeostasis or by regulating muscle atrophy. PMID- 26136414 TI - The delayed recovery of the remobilized rat tibialis anterior muscle reflects a defect in proliferative and terminal differentiation that impairs early regenerative processes. AB - BACKGROUND: The immobilization-induced tibialis anterior (TA) muscle atrophy worsens after cast removal and is associated with altered extracellular matrix (ECM) composition. The secreted protein acidic and rich in cysteine (Sparc) is an ECM component involved in Akt activation and in beta-catenin stabilization, which controls protein turnover and induces muscle regulatory factors (MRFs), respectively. We hypothesized that ECM alterations may influence these intracellular signalling pathways controlling TA muscle mass. METHODS: Six-month old Wistar rats were subjected to hindlimb cast immobilization for 8 days (I8) or not (I0) and allowed to recover for 1 to 10 days (R1-10). RESULTS: The TA atrophy during remobilization correlated with reduced fibre cross-sectional area and thickening of endomysium. mRNA levels for Sparc increased during remobilization until R10 and for integrin-alpha7 and -beta1 at I8 and R1. Integrin-linked kinase protein levels increased during immobilization and remobilization until R10. This was inversely correlated with changes in Akt phosphorylation. beta-Catenin protein levels increased in the remobilized TA at R1 and R10. mRNA levels of the proliferative MRFs (Myf5 and MyoD) increased at I8 and R1, respectively, without changes in Myf5 protein levels. In contrast, myogenin mRNA levels (a terminal differentiation MRF) decreased at R1, but only increased at R10 in remobilized muscles, as for protein levels. CONCLUSIONS: Altogether, this suggests that the TA inefficiently attempted to preserve regeneration during immobilization by increasing transcription of proliferative MRFs, and that the TA could engage recovery during remobilization only when the terminal differentiation step of regeneration is enhanced. PMID- 26136415 TI - Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling. AB - BACKGROUND: Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post transcriptional neuropeptide Y (NPY) regulation. METHODS: Two tumour cachectic mouse models with different food intake behaviours were used: a C26-colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips). RESULTS: In both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26-TB mice and Lewis lung carcinoma-TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion. CONCLUSIONS: Altered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer-induced eating disorders. PMID- 26136416 TI - Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic. AB - BACKGROUND: Elevated resting energy expenditure (REE) may contribute to weight loss and symptom burden in cancer patients. AIMS: The aim of this study was to compare the velocity of weight loss, symptom burden (fatigue, insomnia, anxiety, and anorexia-combined score as measured by the Edmonton Symptom Assessment Score), high-sensitivity C-reactive protein, and survival among cancer patients referred to a cachexia clinic with hypermetabolism, elevated REE > 110% of predicted, with normal REE. METHODS: A retrospective analysis of 60 advanced cancer patients evaluated in a cachexia clinic for either >5% weight loss or anorexia who underwent indirect calorimetry to measure REE. Patients were dichotomized to either elevated or normal REE. Descriptive statistics were generated, and a two-sample Student's t-tests were used to compare the outcomes between the groups. Kaplan-Meier and Cox regression methodology were used to examine the survival times between groups. RESULTS: Thirty-seven patients (62%) were men, 41 (68%) were White, 59 (98%) solid tumours, predominantly 23 gastrointestinal cancers (38%), with a median age of 60 (95% confidence interval 57.0-62.9). Thirty-five patients (58%) were hypermetabolic. Non-Caucasian patients were more likely to have high REE [odds ratio = 6.17 (1.56, 24.8), P = 0.01]. No statistical difference regarding age, cancer type, gender, active treatment with chemotherapy, and/or radiation between hypermetabolic and normal REE was noted. The velocity of weight loss over a 3 month period (-8.5 kg vs. 7.2 kg, P = 0.68), C-reactive protein (37.3 vs. 55.6 mg/L, P = 0.70), symptom burden (4.2 vs. 4.5, P = 0.54), and survival (288 vs. 276 days, P = 0.68) was not significantly different between high vs. normal REE, respectively. CONCLUSION: Hypermetabolism is common in cancer patients with weight loss and noted to be more frequent in non-Caucasian patients. No association among velocity of weight loss, symptom burden, C-reactive protein, and survival was noted in advanced cancer patients with elevated REE. PMID- 26136417 TI - Understanding and managing cancer-related weight loss and anorexia: insights from a systematic review of qualitative research. AB - The aim of this study was to summarize the existing qualitative literature in order to develop the evidence base for understanding and managing weight loss and anorexia, in order to make recommendations for clinical practice. A systematic search was performed to retrieve English language studies using electronic search and manual checks of selected reference lists. Keywords included qualitative, cancer cachexia, weight loss, anorexia, appetite, malnutrition, food, eating, and drinking. The selection and appraisal of papers were undertaken by two reviewers. Twenty-one qualitative articles were included in the review. There were three major findings emerging from the previous qualitative studies including 'the multidimensionality of weight loss and anorexia experience', 'patients and caregivers' responses to coping with weight loss and anorexia', and 'clinical assessment and management of weight loss and anorexia'. The literature review revealed the multidimensional nature of cachexia and weight loss experience by patients and caregivers, which was not recognized and adequately managed by healthcare professionals. Future research in this area would be helpful in enabling a deeper understanding of the complexity of cachexia and weight loss experience in order to move forward to develop an optimal model of supportive care for patients and caregivers. PMID- 26136418 TI - Open source in cachexia? PMID- 26136420 TI - Control of Macrophage Dynamics as a Potential Therapeutic Approach for Clinical Disorders Involving Chronic Inflammation. AB - Macrophages are a well recognized player of both innate and adaptive immunity and have emerged as a key regulator of systemicmetabolism, hematopoiesis, vasculogenesis, apoptosis, malignancy, and reproduction. Such pleiotropic roles of macrophages are mirrored by their protean features. Upon environmental. challenges, macrophages redistribute and differentiate in situ and contribute to the multiple disease states by exerting protective and pathogenic effects. The environmental challenges include cytokines, chemokines, lipid mediators, and extrinsic insults, such as food and pathogenic bacteria. In addition, homeostasis and the activation state of macrophages are influenced by various metabolites from a commensal microbe that colonizes epithelial and mucosal surfaces, such as the lungs, intestines, and skin. In this review, we describe macrophage differentiation, polarization, and various functions in chronic disease states, including chronic inflammatory bowel disease, tumorigenesis, metabolism and obesity, and central nervous system demyelinating disorders. Controlling the macrophage dynamics to affect the pathologic states is considered to be an important therapeutic approach for many clinical disorders involving chronic inflammation. PMID- 26136421 TI - Letter by Gallet and Marban Regarding Article, "Intracoronary Injection of Large Stem Cells: Size Matters". PMID- 26136422 TI - Response to Letter Regarding Article, "Intracoronary Injection of Large Stem Cells: Size Matters". PMID- 26136423 TI - Self-Healing Materials from V- and H-Shaped Supramolecular Architectures. AB - Integrating self-healing capability into supramolecular architectures is an interesting strategy, and can considerably enhance the performance and broaden the scope of applications for this important class of polymers. Herein we report the rational design of novel V-shaped barbiturate (Ba) functionalized soft-hard soft triblock copolymers with a reversible supramolecular healing motif (Ba) in the central part of the hard block, which undergoes autonomic repair at 30 degrees C. The designed synthesis also offers a suitable macromolecular building block to further self-assemble with heterocomplementary alpha,omega-Hamilton wedge (HW) functionalized polyisoprene (PI; HW-PI-HW), resulting in an H-shaped supramolecular architecture with efficient self-healing capabilities that can recover up to around 95 % of the original mechanical performance at 30 degrees C within 24 h. PMID- 26136424 TI - H3K9 Trimethylation Silences Fas Expression To Confer Colon Carcinoma Immune Escape and 5-Fluorouracil Chemoresistance. AB - The Fas-FasL effector mechanism plays a key role in cancer immune surveillance by host T cells, but metastatic human colon carcinoma often uses silencing Fas expression as a mechanism of immune evasion. The molecular mechanism under FAS transcriptional silencing in human colon carcinoma is unknown. We performed genome-wide chromatin immunoprecipitation sequencing analysis and identified that the FAS promoter is enriched with H3K9me3 in metastatic human colon carcinoma cells. The H3K9me3 level in the FAS promoter region is significantly higher in metastatic than in primary cancer cells, and it is inversely correlated with Fas expression level. We discovered that verticillin A is a selective inhibitor of histone methyltransferases SUV39H1, SUV39H2, and G9a/GLP that exhibit redundant functions in H3K9 trimethylation and FAS transcriptional silencing. Genome-wide gene expression analysis identified FAS as one of the verticillin A target genes. Verticillin A treatment decreased H3K9me3 levels in the FAS promoter and restored Fas expression. Furthermore, verticillin A exhibited greater efficacy than decitabine and vorinostat in overcoming colon carcinoma resistance to FasL induced apoptosis. Verticillin A also increased DR5 expression and overcame colon carcinoma resistance to DR5 agonist drozitumab-induced apoptosis. Interestingly, verticillin A overcame metastatic colon carcinoma resistance to 5-fluorouracil in vitro and in vivo. Using an orthotopic colon cancer mouse model, we demonstrated that tumor-infiltrating cytotoxic T lymphocytes are FasL(+) and that FasL mediated cancer immune surveillance is essential for colon carcinoma growth control in vivo. Our findings determine that H3K9me3 of the FAS promoter is a dominant mechanism underlying FAS silencing and resultant colon carcinoma immune evasion and progression. PMID- 26136425 TI - Differential Tissue-Specific Function of Adora2b in Cardioprotection. AB - The adenosine A2b receptor (Adora2b) has been implicated in cardioprotection from myocardial ischemia. As such, Adora2b was found to be critical in ischemic preconditioning (IP) or ischemia/reperfusion (IR) injury of the heart. Whereas Adora2b is present on various cells types, the tissue-specific role of Adora2b in cardioprotection is still unknown. To study the tissue-specific role of Adora2b signaling on inflammatory cells, endothelia, or myocytes during myocardial ischemia in vivo, we intercrossed floxed Adora2b mice with Lyz2-Cre(+), VE cadherin-Cre(+), or myosin-Cre(+) transgenic mice, respectively. Mice were exposed to 60 min of myocardial ischemia with or without IP (four times for 5 min) followed by 120 min of reperfusion. Cardioprotection by IP was abolished in Adora2b(f/f)-VE-cadherin-Cre(+) or Adora2b(f/f)-myosin-Cre(+), indicating that Adora2b signaling on endothelia or myocytes mediates IP. In contrast, primarily Adora2b signaling on inflammatory cells was necessary to provide cardioprotection in IR injury, indicated by significantly larger infarcts and higher troponin levels in Adora2b(f/f)-Lyz2-Cre(+) mice only. Cytokine profiling of IR injury in Adora2b(f/f)-Lyz2-Cre(+) mice pointed toward polymorphonuclear neutrophils (PMNs). Analysis of PMNs from Adora2b(f/f)-Lyz2-Cre(+) confirmed PMNs as one source of identified tissue cytokines. Finally, adoptive transfer of Adora2b(-/-) PMNs revealed a critical role of Adora2b on PMNs in cardioprotection from IR injury. Adora2b signaling mediates different types of cardioprotection in a tissue-specific manner. These findings have implications for the use of Adora2b agonists in the treatment or prevention of myocardial injury by ischemia. PMID- 26136426 TI - Tetraspanin CD151 Is a Negative Regulator of FcepsilonRI-Mediated Mast Cell Activation. AB - Mast cells are critical in the pathogenesis of allergic disease due to the release of preformed and newly synthesized mediators, yet the mechanisms controlling mast cell activation are not well understood. Members of the tetraspanin family are recently emerging as modulators of FcepsilonRI-mediated mast cell activation; however, mechanistic understanding of their function is currently lacking. The tetraspanin CD151 is a poorly understood member of this family and is specifically induced on mouse and human mast cells upon FcepsilonRI aggregation but its functional effects are unknown. In this study, we show that CD151 deficiency significantly exacerbates the IgE-mediated late phase inflammation in a murine model of passive cutaneous anaphylaxis. Ex vivo, FcepsilonRI stimulation of bone marrow-derived mast cells from CD151(-/-) mice resulted in significantly enhanced expression of proinflammatory cytokines IL-4, IL-13, and TNF-alpha compared with wild-type controls. However, FcepsilonRI induced mast cell degranulation was unaffected. At the molecular signaling level, CD151 selectively regulated IgE-induced activation of ERK1/2 and PI3K, associated with cytokine production, but had no effect on the phospholipase Cgamma1 signaling, associated with degranulation. Collectively, our data indicate that CD151 exerts negative regulation over IgE-induced late phase responses and cytokine production in mast cells. PMID- 26136427 TI - BTB-ZF Protein Znf131 Regulates Cell Growth of Developing and Mature T Cells. AB - Many members of the BTB-ZF family have been shown to play important roles in lymphocyte development and function. The role of zinc finger Znf131 (also known as Zbtb35) in T cell lineage was elucidated through the production of mice with floxed allele to disrupt at different stages of development. In this article, we present that Znf131 is critical for T cell development during double-negative to double-positive stage, with which significant cell expansion triggered by the pre TCR signal is coupled. In mature T cells, Znf131 is required for the activation of effector genes, as well as robust proliferation induced upon TCR signal. One of the cyclin-dependent kinase inhibitors, p21(Cip1) encoded by cdkn1a gene, is one of the targets of Znf131. The regulation of T cell proliferation by Znf131 is in part attributed to its suppression on the expression of p21(Cip1). PMID- 26136428 TI - Galectin-3 Binding Protein Secreted by Breast Cancer Cells Inhibits Monocyte Derived Fibrocyte Differentiation. AB - To metastasize, tumor cells often need to migrate through a layer of collagen containing scar tissue which encapsulates the tumor. A key component of scar tissue and fibrosing diseases is the monocyte-derived fibrocyte, a collagen secreting profibrotic cell. To test the hypothesis that invasive tumor cells may block the formation of the fibrous sheath, we determined whether tumor cells secrete factors that inhibit monocyte-derived fibrocyte differentiation. We found that the human metastatic breast cancer cell line MDA-MB-231 secretes activity that inhibits human monocyte-derived fibrocyte differentiation, whereas less aggressive breast cancer cell lines secrete less of this activity. Purification indicated that Galectin-3 binding protein (LGALS3BP) is the active factor. Recombinant LGALS3BP inhibits monocyte-derived fibrocyte differentiation, and immunodepletion of LGALS3BP from MDA-MB 231 conditioned media removes the monocyte-derived fibrocyte differentiation-inhibiting activity. LGALS3BP inhibits the differentiation of monocyte-derived fibrocytes from wild-type mouse spleen cells, but not from SIGN-R1(-/-) mouse spleen cells, suggesting that CD209/SIGN R1 is required for the LGALS3BP effect. Galectin-3 and galectin-1, binding partners of LGALS3BP, potentiate monocyte-derived fibrocyte differentiation. In breast cancer biopsies, increased levels of tumor cell-associated LGALS3BP were observed in regions of the tumor that were invading the surrounding stroma. These findings suggest LGALS3BP and galectin-3 as new targets to treat metastatic cancer and fibrosing diseases. PMID- 26136430 TI - Differential TGF-beta Signaling in Glial Subsets Underlies IL-6-Mediated Epileptogenesis in Mice. AB - TGF-beta1 is a master cytokine in immune regulation, orchestrating both pro- and anti-inflammatory reactions. Recent studies show that whereas TGF-beta1 induces a quiescent microglia phenotype, it plays a pathogenic role in the neurovascular unit and triggers neuronal hyperexcitability and epileptogenesis. In this study, we show that, in primary glial cultures, TGF-beta signaling induces rapid upregulation of the cytokine IL-6 in astrocytes, but not in microglia, via enhanced expression, phosphorylation, and nuclear translocation of SMAD2/3. Electrophysiological recordings show that administration of IL-6 increases cortical excitability, culminating in epileptiform discharges in vitro and spontaneous seizures in C57BL/6 mice. Intracellular recordings from layer V pyramidal cells in neocortical slices obtained from IL-6 -: treated mice show that during epileptogenesis, the cells respond to repetitive orthodromic activation with prolonged after-depolarization with no apparent changes in intrinsic membrane properties. Notably, TGF-beta1 -: induced IL-6 upregulation occurs in brains of FVB/N but not in brains of C57BL/6 mice. Overall, our data suggest that TGF-beta signaling in the brain can cause astrocyte activation whereby IL-6 upregulation results in dysregulation of astrocyte -: neuronal interactions and neuronal hyperexcitability. Whereas IL-6 is epileptogenic in C57BL/6 mice, its upregulation by TGF-beta1 is more profound in FVB/N mice characterized as a relatively more susceptible strain to seizure-induced cell death. PMID- 26136431 TI - The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors. AB - Cyclin B1 (CCNB1) is considered as a potential target for a cancer vaccine, as it is overexpressed in many malignant cells, while being transiently expressed in normal cells. To evaluate the CD4 T cell response to CCNB1, we derived T cell lines by multiple weekly rounds of stimulation with recombinant CCNB1 of T cells collected in healthy donors (long-term T cell assays). T cell lines were specific for 15 immunodominant peptides and derived preferentially from naive T cells. From 74 overlapping peptides, 20 peptides were selected for their broad specificity of binding to HLA class II molecules and included most of the immunodominant epitopes. They primed in vitro a large number of specific CD4 T cell lines in all the donors. Immunodominant epitopes were the most efficacious in long-term T cell assays, both in terms of number of specific T cell lines and number of responding donors. The 20 peptides were also submitted to short-term T cell assays using cells collected in healthy and cancer patients with the aim to evaluate the memory response. The recognized peptides differed from the immunodominant peptides and were part of the best promiscuous peptides. We also observed pre-existing CCNB1-specifc IgG Abs in both healthy and cancer donors. Long- and short-term T cell assays revealed that CCNB1 contained many CD4 T cell epitopes, which are differentially recognized by pre-existing naive and memory CD4 T cells. These observations are of value for the design of cancer vaccines. PMID- 26136429 TI - TLR-9 and IL-15 Synergy Promotes the In Vitro Clonal Expansion of Chronic Lymphocytic Leukemia B Cells. AB - Clinical progression of B cell chronic lymphocytic leukemia (B-CLL) reflects the clone's Ag receptor (BCR) and involves stroma-dependent B-CLL growth within lymphoid tissue. Uniformly elevated expression of TLR-9, occasional MYD88 mutations, and BCR specificity for DNA or Ags physically linked to DNA together suggest that TLR-9 signaling is important in driving B-CLL growth in patients. Nevertheless, reports of apoptosis after B-CLL exposure to CpG oligodeoxynucleotide (ODN) raised questions about a central role for TLR-9. Because normal memory B cells proliferate vigorously to ODN+IL-15, a cytokine found in stromal cells of bone marrow, lymph nodes, and spleen, we examined whether this was true for B-CLL cells. Through a CFSE-based assay for quantitatively monitoring in vitro clonal proliferation/survival, we show that IL 15 precludes TLR-9-induced apoptosis and permits significant B-CLL clonal expansion regardless of the clone's BCR mutation status. A robust response to ODN+IL-15 was positively linked to presence of chromosomal anomalies (trisomy-12 or ataxia telangiectasia mutated anomaly + del13q14) and negatively linked to a very high proportion of CD38(+) cells within the blood-derived B-CLL population. Furthermore, a clone's intrinsic potential for in vitro growth correlated directly with doubling time in blood, in the case of B-CLL with Ig H chain V region-unmutated BCR and <30% CD38(+) cells in blood. Finally, in vitro high proliferator status was statistically linked to diminished patient survival. These findings, together with immunohistochemical evidence of apoptotic cells and IL-15-producing cells proximal to B-CLL pseudofollicles in patient spleens, suggest that collaborative ODN and IL-15 signaling may promote in vivo B-CLL growth. PMID- 26136433 TI - Enhanced Hydrogen Production from DNA-Assembled Z-Scheme TiO2-CdS Photocatalyst Systems. AB - A wide range of inorganic nanostructures have been used as photocatalysts for generating H2. To increase activity, Z-scheme photocatalytic systems have been implemented that use multiple types of photoactive materials and electron mediators. Optimal catalysis has previously been obtained by interfacing different materials through aggregation or epitaxial nucleation, all of which lowers the accessible active surface area. DNA has now been used as a structure directing agent to organize TiO2 and CdS nanocrystals. A significant increase in H2 production compared to CdS or TiO2 alone was thus observed directly in solution with no sacrificial donors or applied bias. The inclusion of benzoquinone (BQ) equidistant between the TiO2 and CdS through DNA assembly further increased H2 production. While the use of a second quinone in conjunction with BQ showed no more improvement, its location within the Z-scheme was found to strongly influence catalysis. PMID- 26136432 TI - Prenatal Allospecific NK Cell Tolerance Hinges on Instructive Allorecognition through the Activating Receptor during Development. AB - Little is known about how the prenatal interaction between NK cells and alloantigens shapes the developing NK cell repertoire toward tolerance or immunity. Specifically, the effect on NK cell education arising from developmental corecognition of alloantigens by activating and inhibitory receptors with shared specificity is uncharacterized. Using a murine prenatal transplantation model, we examined the manner in which this seemingly conflicting input affects NK cell licensing and repertoire formation in mixed hematopoietic chimeras. We found that prenatal NK cell tolerance arose from the elimination of phenotypically hostile NK cells that express an allospecific activating receptor without coexpressing any allospecific inhibitory receptors. Importantly, the checkpoint for the system appeared to occur centrally within the bone marrow during the final stage of NK cell maturation and hinged on the instructive recognition of allogeneic ligand by the activating receptor rather than through the inhibitory receptor as classically proposed. Residual nondeleted hostile NK cells expressing only the activating receptor exhibited an immature, anergic phenotype, but retained the capacity to upregulate inhibitory receptor expression in peripheral sites. However, the potential for this adaptive change to occur was lost in developmentally mature chimeras. Collectively, these findings illuminate the intrinsic process in which developmental allorecognition through the activating receptor regulates the emergence of durable NK cell tolerance and establishes a new paradigm to fundamentally guide future investigations of prenatal NK cell-allospecific education. PMID- 26136434 TI - No association between gingival labial recession and facial type. AB - OBJECTIVE: To evaluate if facial type is a predictor of the development of gingival recession. METHODS: A cohort of 179 orthodontic patients (76 males, 101 females; age before treatment T S = 12.4 years, SD = 0.8) were followed until 5 years post-treatment (T 5 = 20.7 years, SD = 1.2). The presence of recessions was scored ('Yes' or 'No') by two raters on initial (T S), end of treatment (T 0), and post-treatment (T 5) plaster models. A recession was noted (scored 'Yes') if the labial cemento-enamel junction was exposed. The clinical crown heights were measured at T S, T 0, and T 5 as the distances between the incisal edges and the deepest points of the curvature of the vestibulo-gingival margins. Determination of the facial type was based on the inclination of mandibular plane relative to cranial base (Sella-Nasion/Mandibular Plane) and the proportion of posterior to anterior face heights (PFHs; SGo/NMe * 100 per cent) on pre-treatment cephalograms. RESULTS: From T 0 to T 5, the number of subjects with recessions increased from 2 (1.1 per cent) to 24 (13.6 per cent), and the number of recession sites increased from 2 to 39. However, most patients had either one or two recession sites. The mean clinical crown height of mandibular incisors increased by 0.86mm (SD = 0.82, P < 0.001). Regression analysis showed that mandibular plane inclination had no effect on the development of gingival recession or on the increase of clinical crown heights of mandibular incisors. CONCLUSIONS: Facial type is not a predictor of the occurrence of gingival recession. PMID- 26136436 TI - Cervical vertebral maturation method: growth timing versus growth amount. PMID- 26136435 TI - The effect of orofacial myofunctional treatment in children with anterior open bite and tongue dysfunction: a pilot study. AB - OBJECTIVES: Insufficient attention is given in the literature to the early treatment of anterior open bite (AOB) subjects receiving orofacial myofunctional therapy (OMT), which aims to harmonize the orofacial functions. This prospective pilot study investigates the effects of OMT on tongue behaviour in children with AOB and a visceral swallowing pattern. MATERIALS AND METHODS: The study comprised of 22 children (11 boys, 11 girls; age range: 7.1-10.6 years). They were randomly assigned into OMT and non-OMT subjects. The randomization was stratified on the presence of a transversal crossbite. At baseline (T0), at the end of treatment (T1) and at 6 months after T1 (T2) maximum tongue elevation strength was measured with the IOPI system (IOPI MEDICAL LLC, Redmond, Washington, USA). Functional characteristics such as tongue posture at rest, swallowing pattern and articulation and the presence of an AOB were observed. RESULTS: OMT did significantly change tongue elevation strength, tongue posture at rest, and tongue position during swallowing of solid food. At T2 more OMT subjects had contact between the lower central incisors and their antagonists or palate (P = 0.036). More OMT subjects performed a physiological pattern of water swallowing than non-OMT children at T1 and T2, although the differences were not significant. Articulation of /s,l,n,d,t/ was not improved by OMT. No interaction between OMT and expansion was found for any of the parameters. CONCLUSION: OMT can positively influence tongue behaviour. However, further research is recommended to clarify the success of OMT as an adjunct to orthodontic treatment and to identify possible factors influencing the outcome. PMID- 26136437 TI - The effect of different concentrations of topical ozone administration on bone formation in orthopedically expanded suture in rats. AB - BACKGROUND/OBJECTIVE: The aim of this study was to investigate the effects of different concentrations of ozone (O3) therapy on bone regeneration in response to an expansion of the inter-premaxillary suture in rats. MATERIALS AND METHODS: Forty-eight Wistar rats were randomly divided into four groups (n = 12). In groups I, II, and III, 1ml of O3 at 10, 25, and 40 ug/ml was injected at the premaxillary suture, respectively. In group IV (control group), 1ml of saline solution was injected at the same point during the expansion procedure for 5 days. Bone regeneration in the suture was evaluated histomorphometrically. The area of new bone and fibrotic area, the number of osteoblasts and osteoclasts, and the amount of vascularity were measured and compared. The density of the newly formed bone in the expansion area was measured by using cone beam computed tomography. Data were analyzed using the Kruskal-Wallis one-way analysis of variance and post hoc Student-Newman-Keuls tests. RESULTS: New bone area, fibrotic area, osteoblast and osteoclast numbers, and the amount of vascularity were significantly higher in experimental groups compared with the control group (P < 0.001). The density of newly formed bone (P < 0.001), new bone formation (P = 0.009), number of capillaries (P < 0.001), number of osteoclasts (P = 0.016), and number of osteoblasts (P < 0.001) in the maxillary sutures were highest in the 25 MUg/ml O3 group compared with the other experimental groups and control group. CONCLUSIONS/IMPLICATIONS: The application of O3 therapy can stimulate bone regeneration in an orthopedically expanded inter-premaxillary suture during both the expansion and retention periods. PMID- 26136438 TI - Randomized controlled trial: the gold standard or an unobtainable fallacy? AB - BACKGROUND: This article is the result of a debate at the European Journal of Orthodontics Open Session in 2013 in Reykjavik, Iceland. OBJECTIVE: The aim of this article is to highlight some of the strengths and weakness of clinical orthodontic research, with particular emphasis on randomized controlled trials (RCT). The ultimate aim of improving clinical orthodontic research in general. DESIGN: This article is organized into two sections with arguments for and against RCTs. The backgrounds to evidence-based evaluation and the level or quality of evidence in trials are discussed. The article emphasises what makes high quality clinical research, and gives practical advice including examples of tips and potential pitfalls for those undertaking clinical research. RESULTS AND CONCLUSION: The overriding message is constructive and it is hoped that the article serves as an aid in evaluating, designing, conducting, and reporting clinical research. PMID- 26136439 TI - Effectiveness of the open bite treatment in growing children and adolescents. A systematic review. AB - BACKGROUND: The extensive literature concerning the early treatment of anterior open bite (AOB) is still controversial and covers a wide variety of therapeutic approaches. OBJECTIVES: The objective of this study was to provide a comprehensive review evaluating the effectiveness of the orthodontic correction of AOB in growing individuals. SEARCH METHODS: Search was conducted on PubMed, Embase, Cochrane Library, Web of Science, Scopus, Google Scholar, Scielo, and Lilacs databases. Trials registries were consulted for ongoing trials, and grey literature was also contemplated. SELECTION CRITERIA: Selection process was performed to include controlled trials enrolling growing subjects who underwent orthodontic treatment to correct AOB and/or hyperdivergent facial pattern. DATA COLLECTION AND ANALYSIS: Data were grouped and analysed descriptively. Qualitative appraisal was performed according to the Cochrane risk of bias tool, for randomized clinical trials (RCTs), and MINORS tool for non-RCTs. RESULTS: The 22 studies included in this review mostly considered mixed dentition subjects, and there was a considerable variation regarding therapeutic approaches. Because of poor-quality and/or insufficient evidence, consistent results were not found. However, some useful clinical inferences and suggestions for future studies were provided for each therapeutic modality considered here. CONCLUSIONS: Additional efforts must still be directed to perform, whenever possible, RCTs; or to conduct prospective controlled trials with adequate sample sizes, consecutively assembled subjects, with the comparison of contemporary and equivalent groups. PMID- 26136440 TI - Atlantic forest bird communities provide different but not fewer functions after habitat loss. AB - Habitat loss often reduces the number of species as well as functional diversity. Dramatic effects to species composition have also been shown, but changes to functional composition have so far been poorly documented, partly owing to a lack of appropriate indices. We here develop three new community indices (i.e. functional integrity, community integrity of ecological groups and community specialization) to investigate how habitat loss affects the diversity and composition of functional traits and species. We used data from more than 5000 individuals of 137 bird species captured in 57 sites in the Brazilian Atlantic Forest, a highly endangered biodiversity hotspot.Results indicate that habitat loss leads to a decrease in functional integrity while measures of functional diversity remain unchanged or are even positively affected. Changes to functional integrity were caused by (i) a decrease in the provisioning of some functions, and an increase in others; (ii) strong within-guild species turnover; and (iii) a replacement of specialists by generalists. Hence, communities from more deforested sites seem to provide different but not fewer functions. We show the importance of investigating changes to both diversity and composition of functional traits and species, as the effects of habitat loss on ecosystem functioning may be more complex than previously thought. Crucially, when only functional diversity is assessed, important changes to ecological functions may remain undetected and negative effects of habitat loss underestimated, thereby imperiling the application of effective conservation actions. PMID- 26136441 TI - Perceiving polarization with the naked eye: characterization of human polarization sensitivity. AB - Like many animals, humans are sensitive to the polarization of light. We can detect the angle of polarization using an entoptic phenomenon called Haidinger's brushes, which is mediated by dichroic carotenoids in the macula lutea. While previous studies have characterized the spectral sensitivity of Haidinger's brushes, other aspects remain unexplored. We developed a novel methodology for presenting gratings in polarization-only contrast at varying degrees of polarization in order to measure the lower limits of human polarized light detection. Participants were, on average, able to perform the task down to a threshold of 56%, with some able to go as low as 23%. This makes humans the most sensitive vertebrate tested to date. Additionally, we quantified a nonlinear relationship between presented and perceived polarization angle when an observer is presented with a rotatable polarized light field. This result confirms a previous theoretical prediction of how uniaxial corneal birefringence impacts the perception of Haidinger's brushes. The rotational dynamics of Haidinger's brushes were then used to calculate corneal retardance.We suggest that psychophysical experiments, based upon the perception of polarized light, are amenable to the production of affordable technologies for self-assessment and longitudinal monitoring of visual dysfunctions such as age-related macular degeneration. PMID- 26136442 TI - Foundation species' overlap enhances biodiversity and multifunctionality from the patch to landscape scale in southeastern United States salt marshes. AB - Although there is mounting evidence that biodiversity is an important and widespread driver of ecosystem multifunctionality, much of this research has focused on small-scale biodiversity manipulations. Hence, which mechanisms maintain patches of enhanced biodiversity in natural systems and if these patches elevate ecosystem multifunctionality at both local and landscape scales remain outstanding questions. In a 17 month experiment conducted within southeastern United States salt marshes, we found that patches of enhanced biodiversity and multifunctionality arise only where habitat-forming foundation species overlap- i.e. where aggregations of ribbed mussels (Geukensia demissa) form around cordgrass (Spartina alterniflora) stems. By empirically scaling up our experimental results to the marsh platform at 12 sites, we further show that mussels--despite covering only approximately 1% of the marsh surface--strongly enhance five distinct ecosystem functions, including decomposition, primary production and water infiltration rate, at the landscape scale. Thus, mussels create conditions that support the co-occurrence of high densities of functionally distinct organisms within cordgrass and, in doing so, elevate salt marsh multifunctionality from the patch to landscape scale. Collectively, these findings suggest that patterns in foundation species' overlap drive variation in biodiversity and ecosystem functioning within and across natural ecosystems.We therefore argue that foundation species should be integrated in our conceptual understanding of forces that moderate biodiversity--ecosystem functioning relationships, approaches for conserving species diversity and strategies to improve the multifunctionality of degraded ecosystems. PMID- 26136443 TI - Pelagic seabird flight patterns are consistent with a reliance on olfactory maps for oceanic navigation. AB - Homing studies have provided tantalizing evidence that the remarkable ability of shearwaters (Procellariiformes) to pinpoint their breeding colony after crossing vast expanses of featureless open ocean can be attributed to their assembling cognitive maps of wind-borne odours but crucially, it has not been tested whether olfactory cues are actually used as a system for navigation. Obtaining statistically important samples of wild birds for use in experimental approaches is, however, impossible because of invasive sensory manipulation. Using an innovative non-invasive approach, we provide strong evidence that shearwaters rely on olfactory cues for oceanic navigation. We tested for compliance with olfactory-cued navigation in the flight patterns of 210 shearwaters of three species (Cory's shearwaters, Calonectris borealis, North Atlantic Ocean, Scopoli's shearwaters, C. diomedea Mediterranean Sea, and Cape Verde shearwaters, C. edwardsii, Central Atlantic Ocean) tagged with high-resolution GPS loggers during both incubation and chick rearing.We found that most (69%) birds displayed exponentially truncated scale-free(Levy-flight like) displacements, which we show are consistent with olfactory-cued navigation in the presence of atmospheric turbulence. Our analysis provides the strongest evidence yet for cognitive odour map navigation in wild birds. Thus, we may reconcile two highly disputed questions in movement ecology, by mechanistically connecting Levy displacements and olfactory navigation. Our approach can be applied to any species which can be tracked at sufficient spatial resolution, using a GPS logger. PMID- 26136444 TI - Modelling the multidimensional niche by linking functional traits to competitive performance. AB - Linking competitive outcomes to environmental conditions is necessary for understanding species' distributions and responses to environmental change. Despite this importance, generalizable approaches for predicting competitive outcomes across abiotic gradients are lacking, driven largely by the highly complex and context-dependent nature of biotic interactions. Here, we present and empirically test a novel niche model that uses functional traits to model the niche space of organisms and predict competitive outcomes of co-occurring populations across multiple resource gradients. The model makes no assumptions about the underlying mode of competition and instead applies to those settings where relative competitive ability across environments correlates with a quantifiable performance metric. To test the model, a series of controlled microcosm experiments were conducted using genetically related strains of a widespread microbe. The model identified trait microevolution and performance differences among strains, with the predicted competitive ability of each organism mapped across a two-dimensional carbon and nitrogen resource space. Areas of coexistence and competitive dominance between strains were identified,and the predicted competitive outcomes were validated in approximately 95% of the pairings. By linking trait variation to competitive ability, our work demonstrates a generalizable approach for predicting and modelling competitive outcomes across changing environmental contexts. PMID- 26136445 TI - Non-breeding season habitat quality mediates the strength of density-dependence for a migratory bird. AB - Our understanding of when natural populations are regulated during their annual cycle is limited, particularly for migratory species. This information is needed for parametrizing models that can inform management and conservation. Here, we use 14 years of data on colour-marked birds to investigate how conspecific density and habitat quality during the tropical non-breeding period interact to affect body condition and apparent annual survival of a long-distance migratory songbird, the American redstart (Setophagaruticilla). Body condition and survival of birds in high-quality mangrove habitat declined as density increased. By contrast, body condition improved and survival did not vary as density increased in adjacent, lower quality scrub habitat, although mean condition and survival were almost always lower than in mangrove. High rainfall enhanced body condition in scrub but not in mangrove, suggesting factors such as food availability outweighed consequences of crowding in lower quality habitat. Thus, survival of overwintering redstarts in mangrove habitat, disproportionately males,appears to be regulated by a crowding mechanism based on density-dependent resource competition. Survival of individuals in scrub, mostly females, appears to be limited by density-independent environmental factors but not regulated by crowding. The contrasting effects of density and food limitation on individuals overwintering in adjacent habitats illustrate the complexity of processes operating during the non-breeding period for migratory animals, and emphasize the need for long-term studies of animals in multiple habitats and throughout their annual cycles. PMID- 26136446 TI - Hypodermic self-insemination as a reproductive assurance strategy. AB - Self-fertilization occurs in a broad range of hermaphroditic plants and animals, and is often thought to evolve as a reproductive assurance strategy under ecological conditions that disfavour or prevent outcrossing. Nevertheless,selfing ability is far from ubiquitous among hermaphrodites, and may be constrained in taxa where the male and female gametes of the same individual cannot easily meet. Here, we report an extraordinary selfing mechanism in one such species, the free living flatworm Macrostomum hystrix. To test the hypothesis that adaptations to hypodermic insemination of the mating partner under outcrossing also facilitate selfing, we experimentally manipulated the social environment of these transparent flatworms and then observed the spatial distribution of received sperm in vivo. We find that this distribution differs radically between conditions allowing or preventing outcrossing, implying that isolated individuals use their needle-like stylet (male copulatory organ) to inject own sperm into their anterior body region, including into their own head, from where they then apparently migrate to the site of (self-)fertilization. Conferring the ability to self could thus be an additional consequence of hypodermic insemination, a widespread fertilization mode that is especially prevalent among simultaneously hermaphroditic animals and probably evolves due to sexual conflict over the transfer and subsequent fate of sperm. PMID- 26136447 TI - When is incomplete epigenetic resetting in germ cells favoured by natural selection? AB - Resetting of epigenetic marks, such as DNA methylation, in germ cells or early embryos is not always complete. Epigenetic states may therefore persist, decay or accumulate across generations. In spite of mounting empirical evidence for incomplete resetting, it is currently poorly understood whether it simply reflects stochastic noise or plays an adaptive role in phenotype determination. Here, we use a simple model to show that incomplete resetting can be adaptive in heterogeneous environments. Transmission of acquired epigenetic states prevents mismatched phenotypes when the environment changes infrequently relative to generation time and when maternal and environmental cues are unreliable. We discuss how these results may help to interpret the emerging data on transgenerational epigenetic inheritance in plants and animals. PMID- 26136448 TI - Polymorphism and division of labour in a socially complex ant: neuromodulation of aggression in the Australian weaver ant, Oecophylla smaragdina. AB - Complex social structure in eusocial insects can involve worker morphological and behavioural differentiation. Neuroanatomical variation may underscore worker division of labour, but the regulatory mechanisms of size-based task specialization in polymorphic species are unknown. The Australian weaver ant, Oecophylla smaragdina, exhibits worker polyphenism: larger major workers aggressively defend arboreal territories, whereas smaller minors nurse brood.Here, we demonstrate that octopamine (OA) modulates worker size-related aggression in O. smaragdina. We found that the brains of majors had significantly higher titres of OA than those of minors and that OA was positively and specifically correlated with the frequency of aggressive responses to non nestmates, a key component of territorial defence. Pharmacological manipulations that effectively switched OA action in major and minor worker brains reversed levels of aggression characteristic of each worker size class. Results suggest that altering OA action is sufficient to produce differences in aggression characteristic of size-related social roles. Neuromodulators therefore may generate variation in responsiveness to task-related stimuli associated with worker size differentiation and collateral behavioural specializations, a significant component of division of labour in complex social systems. PMID- 26136449 TI - Modelling verbal aggression, physical aggression and inappropriate sexual behaviour after acquired brain injury. AB - Understanding the underpinnings of behavioural disturbances following brain injury is of considerable importance, but little at present is known about the relationships between different types of behavioural disturbances. Here, we take a novel approach to this issue by using confirmatory factor analysis to elucidate the architecture of verbal aggression, physical aggression and inappropriate sexual behaviour using systematic records made across an eight-week observation period for a large sample (n = 301) of individuals with a range of brain injuries. This approach offers a powerful test of the architecture of these behavioural disturbances by testing the fit between observed behaviours and different theoretical models. We chose models that reflected alternative theoretical perspectives based on generalized disinhibition (Model 1), a difference between aggression and inappropriate sexual behaviour (Model 2), or on the idea that verbal aggression, physical aggression and inappropriate sexual behaviour reflect broadly distinct but correlated clinical phenomena (Model 3). Model 3 provided the best fit to the data indicating that these behaviours can be viewed as distinct, but with substantial overlap. These data are important both for developing models concerning the architecture of behaviour as well as for clinical management in individuals with brain injury. PMID- 26136450 TI - Reproductive sharing in relation to group and colony-level attributes in a cooperative breeding fish. AB - The degree to which group members share reproduction is dictated by both within group (e.g. group size and composition) and between-group(e.g. density and position of neighbours) characteristics. While many studies have investigated reproductive patterns within social groups, few have simultaneously explored how within-group and between-group social structure influence these patterns. Here, we investigated how group size and composition, along with territory density and location within the colony, influenced parentage in 36 wild groups of a colonial, cooperatively breeding fish Neolamprologus pulcher. Dominant males sired 76% of offspring in their group, whereas dominant females mothered 82% of offspring in their group. Subordinate reproduction was frequent, occurring in 47% of sampled groups. Subordinate males gained more paternity in groups located in high-density areas and in groups with many subordinate males. Dominant males and females in large groups and in groups with many reproductively mature subordinates had higher rates of parentage loss, but only at the colony edge. Our study provides, to our knowledge,the first comprehensive quantification of reproductive sharing among groups of wild N. pulcher, a model species for the study of cooperation and social behaviour. Further, we demonstrate that the frequency of extra-pair parentage differs across small social and spatial scales. PMID- 26136451 TI - Evidence for specificity in symbiont-conferred protection against parasitoids. AB - Many insects harbour facultative symbiotic bacteria, some of which have been shown to provide resistance against natural enemies. One of the best-known protective symbionts is Hamiltonella defensa, which in pea aphid (Acyrthosiphon pisum) confers resistance against attack by parasitoid wasps in the genus Aphidius (Braconidae).We asked (i) whether this symbiont also confers protection against a phylogenetically distant group of parasitoids (Aphelinidae) and (ii) whether there are consistent differences in the effects of bacteria found in pea aphid biotypes adapted to different host plants. We found that some H. defensa strains do provide protection against an aphelinid parasitoid Aphelinus abdominalis. Hamiltonella defensa from the Lotus biotype provided high resistance to A. abdominalis and moderate to low resistance to Aphidius ervi, while the reverse was seen from Medicago biotype isolates. Aphids from Ononis showed no evidence of symbiont-mediated protection against either wasp species and were relatively vulnerable to both. Our results may reflect the different selection pressures exerted by the parasitoid community on aphids feeding on different host plants, and could help explain the maintenance of genetic diversity in bacterial symbionts. PMID- 26136452 TI - Detrimental effects of an autosomal selfish genetic element on sperm competitiveness in house mice. AB - Female multiple mating (polyandry) is widespread across many animal taxa and indirect genetic benefits are a major evolutionary force favouring polyandry. An incentive for polyandry arises when multiple mating leads to sperm competition that disadvantages sperm from genetically inferior mates. A reduction in genetic quality is associated with costly selfish genetic elements (SGEs), and studies in invertebrates have shown that males bearing sex ratio distorting SGEs are worse sperm competitors than wild-type males.We used a vertebrate model species to test whether females can avoid an autosomal SGE, the t haplotype, through polyandry. The t haplotype inhouse mice exhibits strong drive in t heterozygous males by affecting spermatogenesis and is associated with homozygous in utero lethality. We used controlled matings to test the effect of the t haplotype on sperm competitiveness. Regardless of mating order, t heterozygous males sired only 11% of zygotes when competing against wild-type males, suggesting a very strong effect of the t haplotype on sperm quality. We provide, to our knowledge,the first substantial evidence that polyandry ameliorates the harmful effects of an autosomal SGE arising through genetic incompatibility. We discuss potential mechanisms in our study species and the broader implications for the benefits of polyandry. PMID- 26136453 TI - Cross-generational impact of a male murine pheromone 2-sec-butyl-4,5- dihydrothiazole in female mice. AB - The current understanding of the activity of mammalian pheromones is that endocrine and behavioural effects are limited to the exposed individuals. Here, we demonstrate that the nasal exposure of female mice to a male murine pheromone stimulates expansion of mammary glands, leading to prolonged nursing of pups. Subsequent behavioural testing of the pups from pheromone-exposed dams exhibited enhanced learning. Sialic acid components in the milk are known to be involved in brain development. We hypothesized that the offspring might have received more of this key nutrient that promotes brain development. The mRNA for polysialyltransferase, which produces polysialylated neural cell adhesion molecules related to brain development,was increased in the brain of offspring of pheromone-exposed dams at post-natal day 10, while it was not different at embryonic stages, indicating possible differential brain development during early post-natal life. PMID- 26136454 TI - Response of seaward-migrating European eel (Anguilla anguilla) to manipulated flow fields. AB - Anthropogenic structures (e.g. weirs and dams) fragment river networks and restrict the movement of migratory fish. Poor understanding of behavioural response to hydrodynamic cues at structures currently limits the development of effective barrier mitigation measures. This study aimed to assess the effect of flow constriction and associated flow patterns on eel behaviour during downstream migration. In a field experiment, we tracked the movements of 40 tagged adult European eels (Anguilla anguilla) through the forebay of a redundant hydropower intake under two manipulated hydrodynamic treatments. Interrogation of fish trajectories in relation to measured and modeled water velocities provided new insights into behaviour, fundamental for developing passage technologies for this endangered species. Eels rarely followed direct routes through the site. Initially, fish aligned with streamlines near the channel banks and approached the intake semi-passively. A switch to more energetically costly avoidance behaviours occurred on encountering constricted flow, prior to physical contact with structures. Under high water velocity gradients, fish then tended to escape rapidly back upstream, whereas exploratory 'search' behaviour was common when acceleration was low. This study highlights the importance of hydrodynamics in informing eel behaviour. This offers potential to develop behavioural guidance, improve fish passage solutions and enhance traditional physical screening. PMID- 26136455 TI - Correction to 'The false classification of extinction risk in noisy environments'. PMID- 26136456 TI - N-Heterocyclic Olefins as Organocatalysts for Polymerization: Preparation of Well Defined Poly(propylene oxide). AB - The metal-free polymerization of propylene oxide (PO) using a special class of alkene-N-heterocyclic olefins (NHOs)-as catalysts is described. Manipulation of the chemical structure of the NHO organocatalyst allows for the preparation of the poly(propylene oxide) in high yields with high turnover (TON>2000), which renders this the most active metal-free system for the polymerization of PO reported to date. The resulting polyether displays predictable end groups, molar mass, and a low dispersity (D(M)<1.09). NHOs with an unsaturated backbone are essential for polymerization to occur, while substitution at the exocyclic carbon atom has an impact on the reaction pathway and ensures the suppression of side reactions. PMID- 26136457 TI - 15 YEARS OF PARAGANGLIOMA: Pathology of pheochromocytoma and paraganglioma. AB - Pathologists using their routine diagnostic tools can contribute both to the care of patients with pheochromocytoma/paraganglioma and to understanding the pathobiology of the tumors. They can document details of tissue organization and cytology that are accessible only by microscopy and can characterize admixtures of cell types that are morphologically distinct or show differential expression of immunohistochemical markers. Current roles and challenges for pathologists include differential diagnosis, identifying clues to the presence of hereditary disease, and effective communication of pathology information for clinical and research purposes. Future roles will increasingly involve risk stratification, identification of actionable targets for personalized therapies, and aiding the interpretation of molecular tests by helping characterize genetic variants of unknown significance. It remains to be determined to what extent the need for pathology input will be overshadowed by the availability of genetic testing and other molecular analyses at ever-decreasing cost, together with very effective clinical paradigms for risk stratification and patient care. PMID- 26136458 TI - Cardiomyocyte A Disintegrin And Metalloproteinase 17 (ADAM17) Is Essential in Post-Myocardial Infarction Repair by Regulating Angiogenesis. AB - BACKGROUND: A disintegrin and metalloproteinase 17 (ADAM17) is a membrane-bound enzyme that mediates shedding of many membrane-bound molecules, thereby regulating multiple cellular responses. We investigated the role of cardiomyocyte ADAM17 in myocardial infarction (MI). METHODS AND RESULTS: Cardiomyocyte-specific ADAM17 knockdown mice (ADAM17(flox/flox)/alpha-MHC-Cre; f/f/Cre) and parallel controls (ADAM17(flox/flox); f/f) were subjected to MI by ligation of the left anterior descending artery. Post MI, f/f/Cre mice showed compromised survival, higher rates of cardiac rupture, more severe left ventricular dilation, and suppressed ejection fraction compared with parallel f/f-MI mice. Ex vivo ischemic injury (isolated hearts) resulted in comparable recovery in both genotypes. Myocardial vascular density (fluorescent-labeled lectin perfusion and CD31 immunofluorescence staining) was significantly lower in the infarct areas of f/f/Cre-MI compared with f/f-MI mice. Activation of vascular endothelial growth factor receptor 2 (VEGFR2), its mRNA, and total protein levels were reduced in infarcted myocardium in ADAM17 knockdown mice. Transcriptional regulation of VEGFR2 by ADAM17 was confirmed in cocultured cardiomyocyte-fibroblast as ischemia induced VEGFR2 expression was blocked by ADAM17-siRNA. Meanwhile, ADAM17-siRNA did not alter VEGFA bioavailability in the conditioned media. ADAM17 knockdown mice (f/f/Cre-MI) exhibited reduced nuclear factor-kappaB activation (DNA binding) in the infarcted myocardium, which could underlie the suppressed VEGFR2 expression in these hearts. Post MI, inflammatory response was not altered by ADAM17 downregulation. CONCLUSIONS: This study highlights the key role of cardiomyocyte ADAM17 in post-MI recovery by regulating VEGFR2 transcription and angiogenesis, thereby limiting left ventricular dilation and dysfunction. Therefore, ADAM17 upregulation, within the physiological range, could provide protective effects in ischemic cardiomyopathy. PMID- 26136459 TI - Changes in Aortic Wall Structure, Composition, and Stiffness With Continuous-Flow Left Ventricular Assist Devices: A Pilot Study. AB - BACKGROUND: The effects of nonpulsatile flow on the aorta are unknown. Our aim was to examine the structure of the aorta from patients with continuous-flow left ventricular assist devices (LVADs) and directly measure aortic wall composition and stiffness. METHODS AND RESULTS: Age-matched aortic wall samples were collected from consecutive patients with heart failure (HF) at the time of transplantation and compared with nonfailing donor hearts. An unbiased stereological approach was used to quantify aortic morphometry and composition, and biomechanical testing was performed to determine the stress-strain relationship of the vessel. Data were obtained from 4 patients without a left ventricular assist device (HF group: mean age, 58.3+/-8.0 years), 7 patients with a continuous-flow LVAD (HF+LVAD group: mean, 57.7+/-5.6 years), and 3 nonfailing donors (mean, 53.3+/-12.9 years). Compared with HF, the aortic walls from HF+LVAD had an increase in wall thickness, collagen, and smooth muscle content accompanied by a reduction in elastin and mucinous ground-substance content. Stress-strain curves from the aortas revealed increased vessel stiffness in HF+LVAD compared with HF and nonfailing. The physiological modulus of the aorta progressively stiffened from 74.3+/-5.5 kPa in the nonfailing to 134.4+/-35.0 kPa in the HF to 201.7+/-36.4kPa in the HF+LVAD groups (P<0.001). CONCLUSIONS: Among continuous-flow LVAD patients without aortic valve opening, there are changes in the structure and composition of the aorta as well as an increase in aortic wall stiffness compared with age-matched HF patients and nonfailing donors. Further studies examining the role of nonpulsatile blood flow on aortic function and the potential resultant systemic sequelae are needed. PMID- 26136460 TI - Identification of incident poisoning, fracture and burn events using linked primary care, secondary care and mortality data from England: implications for research and surveillance. AB - BACKGROUND: English national injury data collection systems are restricted to hospitalisations and deaths. With recent linkage of a large primary care database, the Clinical Practice Research Datalink (CPRD), with secondary care and mortality data, we aimed to assess the utility of linked data for injury research and surveillance by examining recording patterns and comparing incidence of common injuries across data sources. METHODS: The incidence of poisonings, fractures and burns was estimated for a cohort of 2 147 853 0-24 year olds using CPRD linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality data between 1997 and 2012. Time-based algorithms were developed to identify incident events, distinguishing between repeat follow-up records for the same injury and those for a new event. RESULTS: We identified 42 985 poisoning, 185 517 fracture and 36 719 burn events in linked CPRD-HES-ONS data; incidence rates were 41.9 per 10 000 person-years (95% CI 41.4 to 42.4), 180.8 (179.8-181.7) and 35.8 (35.4-36.1), respectively. Of the injuries, 22 628 (53%) poisonings, 139 662 (75%) fractures and 33 462 (91%) burns were only recorded within CPRD. Only 16% of deaths from poisoning (n=106) or fracture (n=58) recorded in ONS were recorded within CPRD and/or HES records. None of the 10 deaths from burns were recorded in CPRD or HES records. CONCLUSIONS: It is essential to use linked primary care, hospitalisation and deaths data to estimate injury burden, as many injury events are only captured within a single data source. Linked routinely collected data offer an immediate and affordable mechanism for injury surveillance and analyses of population-based injury epidemiology in England. PMID- 26136461 TI - Early opioid prescription and risk of long-term opioid use among US workers with back and shoulder injuries: a retrospective cohort study. AB - The number of prescription opioid overdose deaths has increased dramatically in recent years and many prescribers are unsure how to balance treatment of pain with secondary prevention. Guidelines recommend low-severity injury patients not receive opioids early in the course of their care, but evidence supporting this guideline is limited. Data from 123 096 workers' compensation claims with back and shoulder injuries were analysed to evaluate this guideline. Back and shoulder injury claimants with early opioid use (<=1 month after injury) had 33% lower (95% CI 24% to 41% lower) odds and 29% higher (95% CI 6% to 58% higher) odds, respectively, of long-term opioid use (>3 months) than claimants with late opioid use, after adjusting for key covariates. Stratified analyses indicate that early opioid use does not appear to increase the risk of long-term use except in cases where no diagnosis or only the diagnosis of unspecified shoulder pain is given prior to prescription. PMID- 26136462 TI - The impact of electronic health records on healthcare quality: a systematic review and meta-analysis. AB - OBJECTIVE: To assess the impact of electronic health record (EHR) on healthcare quality, we hence carried out a systematic review and meta-analysis of published studies on this topic. METHODS: PubMed, Web of Knowledge, Scopus and Cochrane Library databases were searched to identify studies that investigated the association between the EHR implementation and process or outcome indicators. Two reviewers screened identified citations and extracted data according to the PRISMA guidelines. Meta-analysis was performed using the random effects model for each indicator. Heterogeneity was quantified using the Cochran Q test and I2 statistics, and publication bias was assessed using the Egger's test. RESULTS: Of the 23 398 citations identified, 47 articles were included in the analysis. Meta analysis showed an association between EHR use and a reduced documentation time with a difference in mean of -22.4% [95% confidence interval (CI) = -38.8 to 6.0%; P < 0.007]. EHR resulted also associated with a higher guideline adherence with a risk ratio (RR) of 1.33 (95% CI = 1.01 to 1.76; P = 0.049) and a lower number of medication errors with an overall RR of 0.46 (95% CI = 0.38 to 0.55; P < 0.001), and adverse drug effects (ADEs) with an overall RR of 0.66 (95% CI = 0.44 to 0.99; P = 0.045). No association with mortality was evident (P = 0.936). High heterogeneity among the studies was evident. Publication bias was not evident. CONCLUSIONS: EHR system, when properly implemented, can improve the quality of healthcare, increasing time efficiency and guideline adherence and reducing medication errors and ADEs. Strategies for EHR implementation should be therefore recommended and promoted. PMID- 26136463 TI - Age- and cause-specific contributions to income difference in life expectancy at birth: findings from nationally representative data on one million South Koreans. AB - BACKGROUND: Income is not frequently used to monitor health equity on a national level largely due to the lack of public data on income. Information on income allows policy makers to identify the economically disadvantaged population in a country directly. We examined differences in life expectancy (LE) at birth by income and quantified age- and cause-specific contributions to the LE differences using national health insurance data. METHODS: Data from a nationally representative sample of 1 097 333 South Koreans (2% of the total population) collected between 2002 and 2010 (39 737 deaths) were used. National health insurance premiums were used to estimate income level. Age- and cause-specific contributions to differences in LE at birth by income were estimated using Arriaga's decomposition method. RESULTS: LE at birth gradually increased with income in both genders. Interquintile income LE differences were 7.93 years in males and 3.82 years in females. Most of LE differentials were attributed to differences in mortality in middle-aged and older adults. Suicide and cerebrovascular accidents were the two leading causes of death contributing the most to income LE differences in both males and females. The top 10 causes of death accounted for over 50% of the total LE differences by income in both genders. Alcohol-related causes of death explained the majority of the gender differences in the income LE differentials. CONCLUSIONS: Income differentials in LE at birth according to national health insurance premiums and data linkage systems could provide a valuable opportunity for monitoring and prioritizing population health inequalities in South Korea. PMID- 26136464 TI - Mortality and work disability in a cohort of Norwegian couples--the HUNT study. AB - BACKGROUND: Poor health is clustered in families, and partners might influence each other. We studied possible consequences of living with a spouse with poor health or unhealthy lifestyle on mortality and work disability. METHODS: In total, 18 943 couples from the HUNT2 Study (1995-97) were linked to national registries and followed until December 2007, identifying deaths and disability pension retirements. Couple's mean exposures were included together with the individual's deviation from the couple mean in discrete time multilevel logistic regression. RESULTS: There was weak evidence of associations between partner's health and risk of dying. Associations between couples slightly exceeded associations within couples for smoking [odds ratio (OR) within 1.57 (95% confidence interval (CI): 1.38-1.78); OR between 1.88 (95% CI: 1.70-2.08), P value for difference 0.027] and education [OR within 1.07 (95% CI: 0.99-1.15); OR between 1.17 (1.11-1.23), P value for difference 0.065]. Indicators of partner's health, such as self-rated health [OR within 3.17 (95% CI: 2.80-3.58); OR between 3.92 (95% CI: 3.50-4.40), P value for difference 0.014], insomnia [OR within 1.39 (95% CI: 1.18-1.64); OR between 2.11 (95% CI: 1.86-2.53), P value for difference <0.001] and symptoms of depression [OR within 1.45 (95% CI: 1.22-1.71); OR between 1.98 (95% CI: 1.69-2.31) P value for difference 0.009] were, however, associated with risk of work disability. Self-rated health and symptoms displayed stronger associations with work disability among partners than reported somatic diseases. CONCLUSIONS: This study did not indicate strong consequences of living with a spouse with poor health or unhealthy lifestyle on mortality. It did, however, indicate associations of partner's health with work disability. PMID- 26136465 TI - Medical school fails to improve Mediterranean diet adherence among medical students. AB - BACKGROUND: The Mediterranean Diet (MeDi) is associated with a reduced risk of several non-communicable chronic diseases. High levels of nutrition knowledge are associated with greater MeDi adherence irrespective of education and other socio economic factors. The present study investigates whether attending medical school changes students' adherence to the MeDi. METHODS: A cross-sectional study was conducted in November-December 2014 using the 16-item KIDMED questionnaire, which inquiries into eating habits. Each respondent's KIDMED index (range 0-12), whose scores reflect 'poor', 'average' or 'good' MeDi adherence, was calculated. Scores were analyzed for gender, age and early/late medical school year. The Mann Whitney U-test and the chi-square test were used for group comparisons. Ordinal logistic regression was applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for changes in MeDi adherence from early to late medical school after adjustment for potential confounders. RESULTS: Participants were 1038 medical students (573 females) aged 18-34 years (mean 21.9 +/- 2.4). There were 20.8% 'poor', 56.5% 'average' and 22.7% 'good' scores. Gender significantly affected scores (P < 0.01). In the ordinal logistic regression model the odds for greater MeDi adherence increased for the female gender (P < 0.05); females were 48% more likely to have a 'good' KIDMED score than their male peers, whereas early/late medical school year did not affect results [adjusted odds ratio (OR) = 0.95; P = 0.15]. CONCLUSIONS: More than 70% of our medical students know very little about healthy eating and the MeDi. However, this knowledge is essential in their future profession both to support therapeutic decision-making and effective preventive actions. PMID- 26136466 TI - Health inequality between immigrants and natives in Spain: the loss of the healthy immigrant effect in times of economic crisis. AB - BACKGROUND: The immigrant population living in Spain grew exponentially in the early 2000s but has been particularly affected by the economic crisis. This study aims to analyse health inequalities between immigrants born in middle- or low income countries and natives in Spain, in 2006 and 2012, taking into account gender, year of arrival and socioeconomic exposures. METHODS: Study of trends using two cross-sections, the 2006 and 2012 editions of the Spanish National Health Survey, including residents in Spain aged 15-64 years (20 810 natives and 2950 immigrants in 2006, 14 291 natives and 2448 immigrants in 2012). Fair/poor self-rated health, poor mental health (GHQ-12 > 2), chronic activity limitation and use of psychotropic drugs were compared between natives and immigrants who arrived in Spain before 2006, adjusting robust Poisson regression models for age and socioeconomic variables to obtain prevalence ratios (PR) and 95% confidence interval (CI). RESULTS: Inequalities in poor self-rated health between immigrants and natives tend to increase among women (age-adjusted PR2006 = 1.39; 95% CI: 1.24-1.56, PR2012 = 1.56; 95% CI: 1.33-1.82). Among men, there is a new onset of inequalities in poor mental health (PR2006 = 1.10; 95% CI: 0.86-1.40, PR2012 = 1.34; 95% CI: 1.06-1.69) and an equalization of the previously lower use of psychotropic drugs (PR2006 = 0.22; 95% CI: 0.11-0.43, PR2012 = 1.20; 95% CI: 0.73 2.01). CONCLUSIONS: Between 2006 and 2012, immigrants who arrived in Spain before 2006 appeared to worsen their health status when compared with natives. The loss of the healthy immigrant effect in the context of a worse impact of the economic crisis on immigrants appears as potential explanation. Employment, social protection and re-universalization of healthcare would prevent further deterioration of immigrants' health status. PMID- 26136467 TI - Relationship Between Blood Concentrations of Hepcidin and Anemia Severity, Mycobacterial Burden, and Mortality Among Patients With HIV-Associated Tuberculosis. AB - BACKGROUND: Anemia is very common in patients with human immunodeficiency virus (HIV)-associated tuberculosis, and hepcidin may be key in mediating this. We explored the relationship between blood hepcidin concentrations and anemia severity, mycobacterial burden and mortality in patients with HIV-associated tuberculosis. METHODS: Consecutive unselected HIV-infected adults in South Africa were systematically investigated for tuberculosis. Three groups were studied: 116 hospitalized inpatients with HIV infection and tuberculosis (hereafter, "hospitalized patients"), 58 ambulatory outpatients with HIV infection and newly diagnosed tuberculosis (hereafter, "ambulatory patients with tuberculosis"), and 58 ambulatory outpatients with HIV infection and without tuberculosis (hereafter, "ambulatory patients without tuberculosis"). Blood hepcidin concentrations were determined for all patients. Vital status at 3 months was determined, and independent predictors of mortality were identified. RESULTS: Median hepcidin concentrations were 38.8 ng/mL among hospitalized patients, 19.1 ng/mL among ambulatory patients with tuberculosis, and 5.9 ng/mL among ambulatory patients without tuberculosis (P < .001). In both groups with HIV-associated tuberculosis, hepcidin concentrations were strongly associated with greater anemia severity. Additionally, strong, graded associations were observed between hepcidin and composite indices of mycobacterial burden and dissemination. Patients dying within 3 months had significantly higher hepcidin concentrations, which independently predicted mortality. CONCLUSIONS: High hepcidin concentrations were strongly associated with disseminated disease, anemia, and poor prognosis in patients with HIV-associated tuberculosis. Hepcidin may be a mechanistically important mediator underlying the high prevalence of severe anemia in these patients. PMID- 26136468 TI - Characterization of Prohibitin 1 as a Host Partner of Vibrio vulnificus RtxA1 Toxin. AB - RtxA1 toxin, which results in cytoskeletal rearrangement, contact cytotoxicity, hemolysis, tissue invasion, and lethality in mice, is the most potent cytotoxic virulence factor of Vibrio vulnificus. Bioinformatics analysis of rtxA1 predicted 4 functional domains that presumably performed discrete functions during host cell killing. V. vulnificus RtxA1 has a unique domain designated as RtxA1-D2, corresponding to amino acids 1951-2574, which is absent in Vibrio cholerae multifunctional-autoprocessing repeats-in-toxin, suggesting that this domain confers specific biological functions to V. vulnificus RtxA1. HeLa cells expressing green fluorescent protein-RtxA1-D2 became round and lost their viability. A yeast 2-hybrid system identified prohibitin (PHB) 1 as the host partner of RtxA1-D2. The specific interaction of RtxA1-D2 with PHB1 was confirmed by performing immunoprecipitation. Interestingly, V. vulnificus RtxA1 up regulated PHB1 expression on the cytoplasmic membrane of host cells. Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways were confirmed as being important in the up-regulation of PHB1 by using inhibitors. Down-regulation of PHB1 by small interfering RNAs decreased the cytotoxicity of RtxA1-D2 against HeLa cells. The pretreatment of an anti-PHB1 antibody impaired the cytotoxicity of V. vulnificus RtxA1. These results suggest that the involvement PHB1 in the RtxA1 cytotoxicity has significant implications for the pathogenesis of V. vulnificus infections. PMID- 26136469 TI - HIV-Associated Tuberculosis: Does the Iron-Regulatory Hormone Hepcidin Connect Anemia With Poor Prognosis? PMID- 26136471 TI - Staphylokinase Control of Staphylococcus aureus Biofilm Formation and Detachment Through Host Plasminogen Activation. AB - Staphylococcus aureus biofilms, a leading cause of persistent infections, are highly resistant to immune defenses and antimicrobial therapies. In the present study, we investigated the contribution of fibrin and staphylokinase (Sak) to biofilm formation. In both clinical S. aureus isolates and laboratory strains, high Sak-producing strains formed less biofilm than strains that lacked Sak, suggesting that Sak prevents biofilm formation. In addition, Sak induced detachment of mature biofilms. This effect depended on plasminogen activation by Sak. Host-derived fibrin, the main substrate cleaved by Sak-activated plasminogen, was a major component of biofilm matrix, and dissolution of this fibrin scaffold greatly increased susceptibility of biofilms to antibiotics and neutrophil phagocytosis. Sak also attenuated biofilm-associated catheter infections in mouse models. In conclusion, our results reveal a novel role for Sak-induced plasminogen activation that prevents S. aureus biofilm formation and induces detachment of existing biofilms through proteolytic cleavage of biofilm matrix components. PMID- 26136470 TI - Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy-Experienced Patients in Europe (CAPRE). AB - BACKGROUND: European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. METHODS: A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. RESULTS: Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P < .001). CONCLUSIONS: These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross resistance. Continued use of these NAs needs to be reconsidered at a pan-European level. PMID- 26136473 TI - Editorial: Nucleic Acids Research annual Web Server Issue in 2015. PMID- 26136472 TI - A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609. AB - Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs. PMID- 26136474 TI - Know Thy Cells: Improving Biomedical Research Reproducibility. PMID- 26136475 TI - Vaccination and narcolepsy: Immune link found? AB - In some children, vaccination against H1N1 influenza spurred production of antibodies to brain receptors linked to the sleep disorder narcolepsy (Ahmed et al., this issue). PMID- 26136477 TI - Severe dystrophic cardiomyopathy caused by the enteroviral protease 2A-mediated C terminal dystrophin cleavage fragment. AB - Enterovirus infection can cause severe cardiomyopathy in humans. The virus encoded 2A protease is known to cleave the cytoskeletal protein dystrophin. It is unclear, however, whether cardiomyopathy results from the loss of dystrophin or is due to the emergence of a dominant-negative dystrophin cleavage product. We show for the first time that the 2A protease-mediated carboxyl-terminal dystrophin cleavage fragment (CtermDys) is sufficient to cause marked dystrophic cardiomyopathy. The sarcolemma-localized CtermDys fragment caused myocardial fibrosis, heightened susceptibility to myocardial ischemic injury, and increased mortality during cardiac stress testing in vivo. CtermDys cardiomyopathy was more severe than in hearts completely lacking dystrophin. In vivo titration of CtermDys peptide content revealed an inverse relationship between the decay of membrane-bound CtermDys and the restoration of full-length dystrophin at the sarcolemma, in support of a physiologically relevant loss of dystrophin function in this model. CtermDys gene titration and dystrophin replacement studies further established a target threshold of 50% membrane-bound intact dystrophin necessary to prevent mice from CtermDys cardiomyopathy. Conversely, the NtermDys fragment did not compete with dystrophin and had no pathological effect. Thus, CtermDys must be localized to the sarcolemma, with intact dystrophin <50% of normal levels, to exert dominant-negative peptide-dependent cardiomyopathy. These data support a two-hit dominant-negative disease mechanism where membrane-associated CtermDys severs the link to cortical actin and inhibits both full-length dystrophin and compensatory utrophin from binding at the membrane. Therefore, membrane-bound CtermDys is a new potential translational target for virus mediated cardiomyopathy. PMID- 26136478 TI - Producing nitric oxide by pulsed electrical discharge in air for portable inhalation therapy. AB - Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for treating pulmonary hypertension in adults and children. In the United States, the average cost of 5 days of inhaled NO for persistent pulmonary hypertension of the newborn is about $14,000. NO therapy involves gas cylinders and distribution, a complex delivery device, gas monitoring and calibration equipment, and a trained respiratory therapy staff. The objective of this study was to develop a lightweight, portable device to serve as a simple and economical method of producing pure NO from air for bedside or portable use. Two NO generators were designed and tested: an offline NO generator and an inline NO generator placed directly within the inspiratory line. Both generators use pulsed electrical discharges to produce therapeutic range NO (5 to 80 parts per million) at gas flow rates of 0.5 to 5 liters/min. NO was produced from air, as well as gas mixtures containing up to 90% O2 and 10% N2. Potentially toxic gases produced in the plasma, including nitrogen dioxide (NO2) and ozone (O3), were removed using a calcium hydroxide scavenger. An iridium spark electrode produced the lowest ratio of NO2/NO. In lambs with acute pulmonary hypertension, breathing electrically generated NO produced pulmonary vasodilation and reduced pulmonary arterial pressure and pulmonary vascular resistance index. In conclusion, electrical plasma NO generation produces therapeutic levels of NO from air. After scavenging to remove NO2 and O3 and filtration to remove particles, electrically produced NO can provide safe and effective treatment of pulmonary hypertension. PMID- 26136476 TI - Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. AB - The sleep disorder narcolepsy is linked to the HLA-DQB1*0602 haplotype and dysregulation of the hypocretin ligand-hypocretin receptor pathway. Narcolepsy was associated with Pandemrix vaccination (an adjuvanted, influenza pandemic vaccine) and also with infection by influenza virus during the 2009 A(H1N1) influenza pandemic. In contrast, very few cases were reported after Focetria vaccination (a differently manufactured adjuvanted influenza pandemic vaccine). We hypothesized that differences between these vaccines (which are derived from inactivated influenza viral proteins) explain the association of narcolepsy with Pandemrix-vaccinated subjects. A mimic peptide was identified from a surface exposed region of influenza nucleoprotein A that shared protein residues in common with a fragment of the first extracellular domain of hypocretin receptor 2. A significant proportion of sera from HLA-DQB1*0602 haplotype-positive narcoleptic Finnish patients with a history of Pandemrix vaccination (vaccine associated narcolepsy) contained antibodies to hypocretin receptor 2 compared to sera from nonnarcoleptic individuals with either 2009 A(H1N1) pandemic influenza infection or history of Focetria vaccination. Antibodies from vaccine-associated narcolepsy sera cross-reacted with both influenza nucleoprotein and hypocretin receptor 2, which was demonstrated by competitive binding using 21-mer peptide (containing the identified nucleoprotein mimic) and 55-mer recombinant peptide (first extracellular domain of hypocretin receptor 2) on cell lines expressing human hypocretin receptor 2. Mass spectrometry indicated that relative to Pandemrix, Focetria contained 72.7% less influenza nucleoprotein. In accord, no durable antibody responses to nucleoprotein were detected in sera from Focetria vaccinated nonnarcoleptic subjects. Thus, differences in vaccine nucleoprotein content and respective immune response may explain the narcolepsy association with Pandemrix. PMID- 26136479 TI - The galectin-1-glycan axis controls sperm fertilizing capacity by regulating sperm motility and membrane hyperpolarization. AB - Lectin-glycan recognition systems play central roles in many physiologic and pathologic processes. We identified a role for galectin-1 (Gal-1), a highly conserved glycan-binding protein, in the control of sperm function. We found that Gal-1 is expressed in the epididymis and associates with sperm during epididymal maturation. Exposure of sperm to Gal-1 resulted in glycan-dependent modulation of the acrosome reaction (AR), a key event in the fertilization process. Gal-1 deficient (Lgals1(-/-)) mice revealed the essential contribution of this lectin for full sperm fertilizing ability both in vitro and in vivo. Mechanistically, Lgals1(-/-) sperm exhibited defects in their ability to develop hyperactivation, a vigorous motility required for penetration of the egg vestments. Moreover, Lgals1(-/-) sperm showed a decreased ability to control cell volume and to undergo progesterone-induced AR, phenotypes that were rescued by exposure of the cells to recombinant Gal-1. Interestingly, the AR defect was associated with a deficiency in sperm membrane potential hyperpolarization. Our study highlights the relevance of the Gal-1-glycan axis in sperm function with critical implications in mammalian reproductive biology. PMID- 26136481 TI - Immunosuppression in the failing and failed transplant kidney: optimizing outcomes. AB - There is little data to guide clinicians on the optimal management of immunosuppression in patients whose kidney transplant has failed and who have returned to dialysis. Nor is there robust data on whether to perform a transplant nephrectomy. Finally, management of late stage chronic kidney disease, including deciding on dialysis initiation, modality and access planning, must occur simultaneously with efforts aimed at preserving the failing kidney and residual renal function for as long as possible. In this article, we will review the evidence on these topics and suggest areas for improvement. PMID- 26136480 TI - The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature. AB - Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the beta-adrenoceptor antagonist propranolol, the mixed alpha-/beta adrenoceptor antagonist labetalol, and the alpha1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders. PMID- 26136482 TI - Patients with Rheumatoid Arthritis in the Australian OPAL Cohort Show Significant Improvement in Disease Activity over 5 Years: A Multicenter Observational Study. AB - OBJECTIVE: To evaluate disease activity trends in a large cohort of Australian patients with rheumatoid arthritis (RA) from 2009 to 2014. METHODS: This is a multicenter, cross-sectional, noninterventional study of patients with RA treated in Australia. Patients with RA treated at participating OPAL (Optimising Patient outcome in Australian RheumatoLogy) clinics were included in the study. Data, deidentified by patient, clinic, and clinician, were identified using a purpose written electronic medical record. Patient demographics, disease onset, medications, and disease measures were analyzed. The Disease Activity Score at 28 joints (DAS28) was used to classify patients into the disease activity states of remission: low disease activity, moderate disease activity (MDA), and high disease activity. Choice of therapy was at the discretion of the treating clinician. RESULTS: At the time of analysis, the database contained 15,679 patients with RA, 8998 of whom fulfilled the inclusion criteria. Mean age was 63.2 years, mean disease duration was 13.8 years, and the majority were women (72.4%). A total of 37,274 individual DAS28-erythrocyte sedimentation rate scores were recorded for the 8998 patients. The frequency of remission increased significantly from 36.7% in 2009 to 53.5% in 2014 (p < 0.001), and that of MDA decreased from 33% (2009) to 22.2% (2014). The use of biologic disease-modifying antirheumatic drugs for the patients in remission increased from 17% in 2009 to 36.9% in 2014. CONCLUSION: Contemporary management of RA in Australia shows improvements in disease activity toward the target of remission over a 5-year period. PMID- 26136483 TI - Is Chronic Pain a Disease in Its Own Right? Discussions from a Pre-OMERACT 2014 Workshop on Chronic Pain. AB - At the pain workshop held prior to the Outcome Measures in Rheumatology (OMERACT) 12 conference, chronic nonmalignant pain (CP) as a "disease" was discussed, in response to growing interest in this concept and in terms of the effect on the OMERACT Filter 2.0 framework. CP is often assessed as a unidimensional outcome measure; however, if CP is a disease, then outcome measures need to define the disease state and identify all its manifestations as well as its effects, as specified by Filter 2.0. The aim was to write a discussion piece, reflecting the workshop contributions and debate, as an important step in opening a dialogue around future OMERACT Filter 2.0 Framework developments. PMID- 26136484 TI - An Internet-based Controlled Trial Aimed to Improve Osteoporosis Prevention among Chronic Glucocorticoid Users. AB - OBJECTIVE: To address the low prevention and treatment rates for those at risk of glucocorticoid-induced osteoporosis (GIOP), we evaluated the influence of a direct-to-patient, Internet-based educational video intervention using "storytelling" on rates of antiosteoporosis medication use among chronic glucocorticoid users who were members of an online pharmacy refill service. METHODS: We identified members who refilled >= 5 mg/day of prednisone (or equivalent) for 90 contiguous days and had no GIOP therapy for >= 12 months. Using patient stories, we developed an online video addressing risk factors and treatment options, and delivered it to members refilling a glucocorticoid prescription. The intervention consisted of two 45-day "Video ON" periods, during which the video automatically appeared at the time of refill, and two 45-day "Video OFF" periods, during which there was no video. Members could also "self initiate" watching the video by going to the video link. We used an interrupted time series design to evaluate the effectiveness of this intervention on GIOP prescription therapies over 6 months. RESULTS: Among 3017 members (64.8%) exposed to the intervention, 59% had measurable video viewing time, of which 3% "self initiated" the video. The GIOP prescription rate in the "Video ON" group was 2.9% versus 2.7% for the "Video OFF" group. There was a nonsignificant trend toward greater GIOP prescription in members who self-initiated the video versus automated viewing (5.7% vs 2.9%, p = 0.1). CONCLUSION: Among adults at high risk of GIOP, prescription rates were not significantly affected by an online educational video presented at the time of glucocorticoid refill. ClinicalTrials.gov Identifier: NCT01378689. PMID- 26136485 TI - Efficacy of Triamcinolone Hexacetonide versus Methylprednisolone Acetate Intraarticular Injections in Knee Osteoarthritis: A Randomized, Double-blinded, 24-week Study. AB - OBJECTIVE: Intraarticular (IA) corticosteroid injections are broadly used in knee osteoarthritis (OA); however, the best corticosteroid agent is not well defined. The aim of the present study was to compare the efficacy of triamcinolone hexacetonide (TH) and methylprednisolone acetate (MA) injections in knee OA. METHODS: Patients with symptomatic knee OA and Kellgren-Lawrence grade II or III were randomized to receive 40 mg of IA TH or MA. Evaluations were performed at 4, 12, and 24 weeks. The primary outcome was a change in the patient's assessment of pain by visual analog scale from baseline to Week 4. Secondary outcomes included a global assessment of the disease by patients and physicians, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne index (LI), and Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of response. Generalized estimating equations were used in statistical analysis. RESULTS: The intention-to treat population included 100 patients; 50 in each study arm. A significant improvement in pain was observed at Week 4 for both groups (p < 0.0001), with no difference between them (p = 0.352). This improvement was sustained up to Week 24. A significant improvement from the baseline was observed for both the patient's and the physician's global assessments, WOMAC questionnaire, and LI, with no differences between the groups. Improvements in the secondary outcomes were sustained during the study. The OMERACT-OARSI criteria of response was achieved by 74% and 72% of patients in the TH and the MA groups, respectively. CONCLUSION: Both IA therapies are equally effective, and improvement in pain and function can be sustained for up to 24 weeks. Controlled-trials.com identifier: ISRCTN15077843. PMID- 26136486 TI - Development of Image Overlay and Knowledge Transfer Module Technologies Aimed at Enhancing Feasibility and External Validation of Magnetic Resonance Imaging-based Scoring Systems. AB - OBJECTIVE: Semiquantitative arthritis scoring assesses disease burden by scoring presence/extent of features such as bone marrow lesion (BML) or effusion in multiple anatomic regions at a joint. An image overlay clarifying region borders may enhance feasibility and reliability of these scoring systems. To be scalable for use in large clinical trials, systematic computer-based user training is desirable. We developed an overlay and user training module for magnetic resonance imaging (MRI)-based scoring of hip osteoarthritis (OA). METHODS: We designed a semitransparent 2-dimensional image overlay applied to individual MRI slices to facilitate hip OA scoring [HIMRISS (Hip Inflammation MRI Scoring System)], initially using freeware and then in a customized HTML Web browser environment. We developed a systematic knowledge translation package including instructional presentation, fully scored expert consensus cases, and video tutorials for training in the use of these scoring systems with the overlays. Three musculoskeletal radiologists who had not used this scoring system before each performed a scoring exercise with no overlay, then repeated this with overlays after completing the training module. Based on postexercise interviews and a reader survey, we identified and corrected problems in the module. The entire training process was then repeated using 3 new readers. RESULTS: Overlays were considered useful, particularly when integrated into a Web browser. The knowledge translation module was considered conceptually valuable, but as initially implemented was too lengthy and not sufficiently interactive. CONCLUSION: Semitransparent image overlays and standardized knowledge translation modules for reader training show promise to facilitate reader calibration using MRI-based scoring systems. Based on our experience, knowledge translation modules should emphasize close feedback evaluating performance and reader time efficiency. PMID- 26136487 TI - Outcome of Patients with Systemic Sclerosis in the Intensive Care Unit. AB - OBJECTIVE: Patients with systemic sclerosis (SSc) are prone to disease-specific or treatment-related life-threatening complications that may warrant intensive care unit (ICU) admission. We assessed the characteristics and current outcome of patients with SSc admitted to the ICU. METHODS: We performed a single-center retrospective study over 6 years (November 2006-December 2012). All patients with SSc admitted to the ICU were enrolled. Short-term (in-ICU and in-hospital) and longterm (6-mo and 1-yr) mortality rates were studied, and the prognostic factors were analyzed. RESULTS: Forty-one patients with a median age of 50 years [interquartile range (IQR) 40-65] were included. Twenty-nine patients (72.5%) displayed diffuse cutaneous SSc. The time from diagnosis to ICU admission was 78 months (IQR 34-128). Twenty-eight patients (71.7%) previously had pulmonary fibrosis, and 12 (31.5%) had pulmonary hypertension. The main reason for ICU admission was acute respiratory failure in 27 patients (65.8%). Noninvasive ventilation was first attempted in 13 patients (31.7%) and was successful in 8 of them, whereas others required endotracheal intubation within 24 h. Altogether, 13 patients (31.7%) required endotracheal intubation and mechanical ventilation. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 31.8%, 39.0%, 46.4%, and 61.0%, respectively. Invasive mechanical ventilation was the worst prognostic factor, associated with an in-hospital mortality rate of 84.6%. CONCLUSION: This study provides reliable prognostic data in patients with SSc who required ICU admission. The devastating outcome of invasive mechanical ventilation in patients with SSc requires a reappraisal of indications for ICU admission and early identification of patients likely to benefit from noninvasive ventilation. PMID- 26136488 TI - Quality of Sexual Life in Women with Primary Sjogren Syndrome. AB - OBJECTIVE: To assess the quality of sexual life of women with primary Sjogren syndrome (pSS) and to identify its correlations with disease activity and damage, quality of life, and mood disorders. METHODS: The quality of sexual life of 24 women with pSS was assessed with the Female Sexual Function Index (FSFI). Twenty four healthy women, matched by age and hormonal status, were enrolled as controls. Mood disorders and quality of life were investigated using the Hospital Anxiety and Depression Scale (HADS) and the Medical Outcomes Study Short Form-36. Patients underwent a gynecological visit with vaginal pH measurement, cervicovaginal swabs, and Pap smears. Disease activity and damage were assessed by the European League Against Rheumatism Sjogren syndrome disease activity and damage indexes. RESULTS: Patients with pSS showed a pathological mean FSFI score (19.1 +/- 7.33) significantly different from controls (p = 0.004), both in menstruating women (p = 0.006) and in menopausal women (p = 0.03). Major differences between the 2 groups were detected in dyspareunia (p < 0.005), lubrication (p = 0.006), desire (p = 0.004), and arousal (p = 0.018). The FSFI score was inversely correlated with age (p = 0.008) and anxiety HADS (p = 0.031). No early anatomical changes, swabs, and Pap smear alterations were revealed in patients with pSS; however, vaginal pH was higher than normal in premenopausal patients (6.0 +/- 0.77). CONCLUSION: Both premenopausal and postmenopausal women with pSS have a worse sexual quality of life. We reported a greater prevalence of dyspareunia that is statistically significant when compared with controls. The FSFI could be a useful tool to assess this topic, but has been neglected in the care of patients with pSS heretofore. PMID- 26136489 TI - Report from the OMERACT Hand Osteoarthritis Working Group: Set of Core Domains and Preliminary Set of Instruments for Use in Clinical Trials and Observational Studies. AB - OBJECTIVE: During OMERACT 12, a workshop was held with the aim to endorse a core set of domains for 3 settings: clinical trials of symptom and structure modification and observational studies. Additional goals were to endorse a core set of contextual factors for these settings, and to define preliminary instruments for each core domain. Finally, an agenda for future research in hand osteoarthritis (OA) was to be proposed. METHODS: Literature reviews of preliminary instruments for each core domain of the proposed core set for hand OA in the settings described above. Literature review of radiographic scoring methods and modern imaging in hand OA were also performed. Proposed contextual factors for a core set were identified through 2 Delphi exercises with participation of hand OA experts, patient partners, and OMERACT participants. RESULTS: Results from Delphi exercises and systematic literature reviews were presented and discussed. It was agreed that a preliminary core domain set for the setting clinical trials of symptom modification should contain at least "pain, physical function, patient global assessment, joint activity and hand strength." The settings clinical trial of structure modification and observational studies would in addition include structural damage. Preliminary instruments for the proposed domains were agreed on. A list of prioritized contextual factors was defined and endorsed for further research. A research agenda was proposed for domain instrument validation according to the OMERACT Filter 2.0. CONCLUSION: Preliminary core sets for clinical trials of symptom and structure modification and observational studies in hand osteoarthritis, including preliminary instruments and contextual factors, were agreed upon during OMERACT 12. PMID- 26136490 TI - Assessment of Patients with Takayasu Arteritis in Routine Practice with Indian Takayasu Clinical Activity Score. AB - OBJECTIVE: To assess the Indian Takayasu Clinical Activity Score (ITAS2010) in followup of Takayasu arteritis (TA). METHODS: ITAS2010 forms were filled in prospectively (n = 144). Clinical activity was assessed with physician's global assessment (PGA) and criteria defined by Kerr, et al. RESULTS: ITAS2010 was significantly higher in patients with active disease. Total agreement between ITAS2010 and PGA was 66.4%, and between ITAS2010 and Kerr, et al was 82.8%. During followup, 14 of 15 patients showing vascular progression with imaging were categorized as having inactive disease according to ITAS2010. CONCLUSION: ITAS2010 was discriminatory for activity during the followup, but the agreement between PGA and ITAS2010 was moderate. Future work should include the incorporation of advanced vascular imaging and demonstration of ITAS2010 as a scalable measure and not simply a dichotomous measure of activity/flare versus remission. PMID- 26136491 TI - Hybrid 18F-labeled Fluoride Positron Emission Tomography/Magnetic Resonance (MR) Imaging of the Sacroiliac Joints and the Spine in Patients with Axial Spondyloarthritis: A Pilot Study Exploring the Link of MR Bone Pathologies and Increased Osteoblastic Activity. AB - OBJECTIVE: The biologically active molecule used in positron emission tomography (PET) for depiction of osteoblastic activity is 18F-labeled fluoride (18F-F). We examined whether inflammatory or chronic changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) and the spines of patients with active ankylosing spondylitis (AS) are linked to osteoblastic activity, assessed by PET/MRI. METHODS: Thirteen patients with AS (mean age 37.8 +/- 11.4 yrs, Bath AS Disease Activity Index > 4, no anti-TNF treatment) underwent 3-Tesla whole-spine and SIJ PET/MRI. Two independent readers recorded pathologic changes related to vertebral (VQ) or SIJ quadrants (SQ). Final scores were based on reader agreement. RESULTS: A total of 104 SQ and 1196 VQ were examined. In SIJ, bone marrow edema (BME) was seen in 44.2%, fat deposition (FD) in 42.3%, and 18F-F in 46.2% SQ. BME alone was associated with 18F-F in 78.6% and FD alone in only 7.7% SQ, while the combination BME/FD was associated with 18F-F in 72.2% SQ. Erosions, sclerosis, and ankylosis alone were rarely associated with 18F-F. In the spine, BME alone was seen in 9.9%, FD in 18.2%, and 18F-F in 5.4% VQ. BME alone was associated with 18F-F in 14.3% and FD alone in 8.7% VQ, while the combination BME/FD was associated with 18F-F in 40.6% VQ. CONCLUSION: In this study of hybrid 18F-F PET/MRI of patients with active AS, we show that BME rather than chronic changes is associated with osteoblastic activity, while the combination of BME and FD showed the highest 18F-F uptake. The use of PET/MRI in prediction of future syndesmophyte formation in AS needs further exploration in prospective studies. PMID- 26136492 TI - Identifying Trajectories of Pain Severity in Early Symptomatic Knee Osteoarthritis: A 5-year Followup of the Cohort Hip and Cohort Knee (CHECK) Study. AB - OBJECTIVE: To identify subgroups of pain trajectories in patients with symptomatic knee osteoarthritis (OA), and to explain these different trajectories by patient characteristics, lifestyle, and coping factors, as well as radiographic features. METHODS: Longitudinal data of pain severity (0-10) from 5 years of followup of the CHECK (Cohort Hip and Cohort Knee) study was used. Latent class growth analysis identified homogeneous subgroups with distinct trajectories of pain. Multinomial regression analysis was used to examine different lifestyle and coping characteristics between the trajectories. RESULTS: In longitudinal pain data of 5 years of followup in 705 participants, 3 pain trajectories were identified: marginal, mild, and moderate pain trajectories. Compared with the marginal pain trajectory, the mild and moderate pain trajectories can be characterized by the following baseline variables: body mass index (BMI) > 25, additional hip pain, low education level, using the coping strategy "worrying," and having >= 3 comorbidities. Moderate pain trajectory can be supplemented with the Kellgren-Lawrence grading scale grade >= 2 radiological change. CONCLUSION: Three trajectories of pain were identified. Participants with a BMI > 25, secondary school as highest education level, having at least 3 comorbidities, additional hip pain, and/or whose coping style is worrying are more likely to develop a moderate or mild pain trajectory compared with those without these characteristics. In the management of knee pain in people with early symptomatic OA, attention should also be given to additional factors such as hip pain, other comorbidities, passive coping strategy, and obesity. PMID- 26136494 TI - Late new morbidity in survivors of adolescent and young-adulthood brain tumors in Finland: a registry-based study. AB - BACKGROUND: Brain tumors (BTs) in adolescence and young adulthood (AYA) differ from those in childhood or late adulthood. However, research concerning late effects in this particular survivor group is limited. This study evaluates late morbidity of survivors diagnosed in AYAs. METHODS: We identified from the Finnish Cancer Registry all survivors diagnosed with BT at the ages 16-24 years between 1970 and 2004 (N = 315) and used data from the Hospital Discharge Registry to evaluate their late (>=5 y after diagnosis) morbidity requiring treatment in a specialized health care setting. A sibling cohort of BT patients diagnosed before the age of 25 years was used as a comparison cohort (N = 3615). RESULTS: The AYA BT survivors had an increased risk for late-appearing endocrine diseases (HR, 2.9; 95% CI, 1.1-8.0), psychiatric disorders (HR, 2.0; 95% CI, 1.2-3.2), diseases of the nervous system (HR, 9; 95% CI, 6.6-14.0), disorders of vision/hearing loss (HR, 3.6; 95% CI, 1.5-8.5), diseases of the circulatory system (HR, 4.9; 95% CI, 2.9-8.1), and diseases of the kidney (HR, 5.9; 95% CI, 2.5-14.1). Survivors with irradiation had an increased risk for diseases of the nervous system compared with non-irradiated survivors (HR, 3.3; 95% CI, 1.8-6.2). The cumulative prevalence for most of the diagnoses remained significantly increased for survivors even 20 years after cancer diagnosis. CONCLUSIONS: The AYA BT survivors have an increased risk of morbidity for multiple new outcomes for >=5 years after their primary diagnosis. This emphasizes the need for structured late-effect follow-up for this patient group. PMID- 26136493 TI - Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation. AB - BACKGROUND: Metabolic complications such as obesity, hyperglycemia, and type 2 diabetes are associated with poor outcomes in patients with glioblastoma. To control peritumoral edema, use of chronic high-dose steroids in glioblastoma patients is common, which can result in de novo diabetic symptoms. These metabolic complications may affect tumors via profound mechanisms, including activation of insulin receptor (InsR) and the related insulin-like growth factor 1 receptor (IGF1R) in malignant cells. METHODS: In the present study, we assessed expression of InsR in glioblastoma surgical specimens and glioblastoma response to insulin at physiologically relevant concentrations. We further determined whether genetic or pharmacological targeting of InsR affected oncogenic functions of glioblastoma in vitro and in vivo. RESULTS: We showed that InsR was commonly expressed in glioblastoma surgical specimens and xenograft tumor lines, with mitogenic isoform-A predominating. Insulin at physiologically relevant concentrations promoted glioblastoma cell growth and survival, potentially via Akt activation. Depletion of InsR impaired cellular functions and repressed orthotopic tumor growth. The absence of InsR compromised downstream Akt activity, but yet stimulated IGF1R expression. Targeting both InsR and IGF1R with dual kinase inhibitors resulted in effective blockade of downstream signaling, loss of cell viability, and repression of xenograft tumor growth. CONCLUSIONS: Taken together, our work suggests that glioblastoma is sensitive to the mitogenic functions of insulin, thus significant insulin exposure imposes risks to glioblastoma patients. Additionally, dual inhibition of InsR and IGF1R exhibits promise for treating glioblastoma. PMID- 26136495 TI - Sublethal Effects of Fenoxycarb on the Plutella xylostella (Lepidoptera: Plutellidae). AB - The effects of fenoxycarb, a Juvenile hormone analogue, at sublethal concentrations were tested on some biological parameters of Plutella xylostella (L.) in two consecutive generations. The calculated LC10, LC25, and LC50 values of the insecticide were 21.58, 43.25, and 93.62 mg/liter on third-instar larvae, respectively. Fenoxycarb significantly reduced pupal weight and oviposition period in parent generation. In addition, the fecundity of treated groups (LC10 = 71.06, LC25 = 40.60 eggs per female) in parents was significantly lower than control (169.40 eggs per female). Although fenoxycarb could not affect gross reproductive rate and death rate, it decreased net reproductive rate, intrinsic rate of increase, finite rate of increase, and birth rate in offspring generation. Also, mean generation time and doubling time of treated insects was significantly longer than control at LC10 level. Therefore, the data from this study suggested that fenoxycarb could adversely cause population decline in the subsequent generation. PMID- 26136496 TI - A Coffee Berry Borer (Coleoptera: Curculionidae: Scolytinae) Bibliography. PMID- 26136497 TI - Phage Therapy is Effective in Protecting Honeybee Larvae from American Foulbrood Disease. AB - American foulbrood disease has a major impact on honeybees (Apis melifera) worldwide. It is caused by a Gram-positive, spore-forming bacterium, Paenibacillus larvae. The disease can only affect larval honeybees, and the bacterial endospores are the infective unit of the disease. Antibiotics are not sufficient to combat the disease due to increasing resistance among P. larvae strains. Because of the durability and virulence of P. larvae endospores, infections spread rapidly, and beekeepers are often forced to burn beehives and equipment. To date, very little information is available on the use of bacteriophage therapy in rescuing and preventing American foulbrood disease, therefore the goal of this study was to test the efficacy of phage therapy against P. larvae infection. Out of 32 previously isolated P. larvae phages, three designated F, WA, and XIII were tested on artificially reared honeybee larvae infected with P. larvae strain NRRL B-3650 spores. The presence of P. larvae DNA in dead larvae was confirmed by 16S rRNA gene-specific polymerase chain reaction amplification. Survival rates for phage-treated larvae were approximately the same as for larvae never infected with spores (84%), i.e., the phages had no deleterious effect on the larvae. Additionally, prophylactic treatment of larvae with phages before spore infection was more effective than administering phages after infection, although survival in both cases was higher than spores alone (45%). Further testing to determine the optimal combination and concentration of phages, and testing in actual hive conditions are needed. PMID- 26136498 TI - Carposina sasakii (Lepidoptera: Carposinidae) in its Native Range Consists of Two Sympatric Cryptic Lineages as Revealed by Mitochondrial COI Gene Sequences. AB - The genetic differentiation and genetic structure of the peach fruit moth, Carposina sasakii Matsumura (Lepidoptera: Carposinidae), was investigated in China, where the moth is native. The mitochondrial cytochrome c oxidase I (COI) gene of 180 individuals from 16 collections were sequenced and analyzed. The results showed that two sympatric and cryptic mtDNA lineages existed within C. sasakii in China. The genetic differentiation has significant correlation with the geographical distance, but has no evidence for host plant associations. Our results of haplotype distribution suggest that the C. sasakii individuals can naturally move between areas, while the movement of individuals between long distance locations may be associated with human activities such as the transport of fruit. Finally, an mitochondrial COI gene PCR-RFLP method was developed to differentiate the two cryptic mtDNA lineages within C. sasakii, which provides rapid and reliable tool for the future research of the two lineages. PMID- 26136499 TI - Contact Toxicity and Repellency of the Main Components From the Essential Oil of Clausena anisum-olens Against Two Stored Product Insects. AB - The essential oil of Clausena anisum-olens (Blanco) Merr. showed strong contact toxicity and repellency against Lasioderma serricorne and Liposcelis bostrychophila adults. The components of the essential oil obtained by hydrodistillation were determined by gas chromatography-mass spectrometry. It was found that the main components were myristicin (36.87%), terpinolene (13.26%), p cymene-8-ol (12.38%), and 3-carene (3.88%). Myristicin and p-cymene-8-ol were separated by silica gel column chromatography, and their molecular structures were confirmed by means of physicochemical and spectrometric analysis. Myristicin and p-cymene-8-ol showed strong contact toxicity against L. serricorne (LD50 = 18.96 and 39.68 MUg per adult) and Li. bostrychophila (LD50 = 20.41 and 35.66 MUg per adult). The essential oil acting against the two grain storage insects showed LD50 values of 12.44 and 74.46 MUg per adult, respectively. Myristicin and p cymene-8-ol have strong repellent toxicity to Li. bostrychophila. PMID- 26136500 TI - Immediate procedural outcomes in 44 consecutive Pipeline Flex cases: the first North American single-center series. AB - BACKGROUND: Flow diversion is an established technique for treatment of cerebral aneurysms. The Pipeline embolization device (PED) is the only FDA-approved flow diverting stent in the USA. A second-generation device, PED Flex, has recently been released with modifications to the delivery system. Published reports of experience with this new device are limited. OBJECTIVE: To describe the initial outcomes from the first North American series using the PED Flex-a single-center experience of 44 cases. METHODS: All patients consecutively treated with the PED Flex embolization device from February 2015 through April 2015 were included in the study. Data were collected for patient demographics, aneurysm characteristics, technical procedural details, and early outcomes. RESULTS: PED Flex treatment was attempted in 42 patients (mean 56.6+/-2.0 years) with 44 aneurysms (mean size 6.5+/-0.6 mm), 41/44 (93%) of which were anterior circulation and 3/44 (7%) were posterior circulation. PED Flex was successfully implanted in 43/44 cases (98%). A single device was used in 41/43 cases (95%), with a mean of 1.07+/-0.05 devices implanted per case. Resheathing was performed in 4/44 cases (9%). Mean postprocedure hospital length of stay was 1.3+/-0.2 days. One significant neurological complication (2.3%) occurred, which was a stroke in a patient non-compliant with the prescribed antiplatelet regimen. CONCLUSIONS: Pipeline Flex is a second-generation flow diverter with enhanced features compared with the first-generation PED. These modifications allow for more reliable deployment with continued improvements in procedural safety. PMID- 26136501 TI - Proceedings: Moving Toward Cell-Based Therapies for Heart Disease. AB - Heart disease due to myocardial infarction and the ensuing heart failure represent a major unmet medical need. Approved treatments do not prevent loss of cardiac muscle or reduce scar formation, both of which weaken heart function. Cell-based therapies currently being investigated both preclinically and clinically have the potential to address these underlying problems either by actually replacing lost tissue or by supplying paracrine growth factors that may have multiple beneficial effects such as reduction of inflammation, increase of blood supply, improvement in cell survival, and reduction of scar size. The best cell types, stage of disease to target, and delivery method to improve heart function are currently unclear. The California Institute for Regenerative Medicine supports multiple different cell-therapy strategies for heart disease, offering hope that improved treatments will be available for patients in the future. PMID- 26136502 TI - Drug Transporter-Mediated Protection of Cancer Stem Cells From Ionophore Antibiotics. AB - Ionophore antibiotics were reported to selectively kill cancer stem cells and to overcome multidrug resistance, but mechanistic studies of the significance of drug transporters for treatment with these compounds are lacking. We applied chemosensitivity testing of well-characterized human cancer cell lines to elaborate on whether drug transporters are involved in protection from the cytotoxic effects of the ionophore antibiotics salinomycin and nigericin. Our experiments demonstrated that ionophore antibiotics were ineffective against both stem-like ovarian cancer side population cells (expressing either ABCB1 or ABCG2) and K562/Dox-H1 cells, which constitute a genetically defined model system for ABCB1 expression. Considering that cancer stem cells often express high levels of drug transporters, we deduced from our results that ionophore antibiotics are less suited to cancer stem cell-targeted treatment than previously thought. SIGNIFICANCE: Ionophore antibiotics such as salinomycin have repeatedly been shown to target cancer stem and progenitor cells from various tumor entities. Meanwhile, cancer stem cell (CSC)-selective toxicity of ionophore antibiotics seems to be a commonly accepted concept that is about to encourage their clinical testing. This study provides data that challenge the concept of targeted elimination of CSC by ionophore antibiotics. Stem-like ovarian cancer side population (SP) cells expressing high levels of ABC drug transporters are shown to largely resist the cytotoxic effects of salinomycin and nigericin. Furthermore, using a small interfering RNA-based knockdown model specific for ABCB1, this study demonstrates that ABC drug transporters are indeed causally involved in mediating protection from ionophore antibiotics. Considering that it is a hallmark of CSCs to exhibit drug resistance conferred by ABC drug transporters, it must be deduced from these results that CSCs may also be protected from ionophore antibiotics by means of drug-transporter mediated efflux. PMID- 26136503 TI - Differentiation of Odontoblast-Like Cells From Mouse Induced Pluripotent Stem Cells by Pax9 and Bmp4 Transfection. AB - The field of tooth regeneration has progressed in recent years, and human tooth regeneration could become viable in the future. Because induced pluripotent stem (iPS) cells can differentiate into odontogenic cells given appropriate conditions, iPS cells are a potential cell source for tooth regeneration. However, a definitive method to induce iPS cell-derived odontogenic cells has not been established. We describe a novel method of odontoblast differentiation from iPS cells using gene transfection. We generated mouse iPS cell-derived neural crest-like cells (iNCLCs), which exhibited neural crest markers. Next, we differentiated iNCLCs into odontoblast-like cells by transfection of Pax9 and Bmp4 expression plasmids. Exogenous Pax9 upregulated expression of Msx1 and dentin matrix protein 1 (Dmp1) in iNCLCs but not bone morphogenetic protein 4 (Bmp4) or dentin sialophosphoprotein (Dspp). Exogenous Bmp4 upregulated expression of Msx1, Dmp1, and Dspp in iNCLCs, but not Pax9. Moreover, cotransfection of Pax9 and Bmp4 plasmids in iNCLCs revealed a higher expression of Pax9 than when Pax9 plasmid was used alone. In contrast, exogenous Pax9 downregulated Bmp4 overexpression. Cotransfection of Pax9 and Bmp4 synergistically upregulated Dmp1 expression; however, Pax9 overexpression downregulated exogenous Bmp4-induced Dspp expression. Together, these findings suggest that an interaction between exogenous Pax9- and Bmp4-induced signaling modulated Dmp1 and Dspp expression. In conclusion, transfection of Pax9 and Bmp4 expression plasmids in iNCLCs induced gene expression associated with odontoblast differentiation, suggesting that iNCLCs differentiated into odontoblast-like cells. The iPS cell-derived odontoblast-like cells could be a useful cell source for tooth regeneration. SIGNIFICANCE: It has been reported that induced pluripotent stem (iPS) cells differentiate into odontogenic cells by administration of recombinant growth factors and coculture with odontogenic cells. Therefore, they can be potential cell sources for tooth regeneration. However, these previous methods still have problems, such as usage of other cell types, heterogeneity of differentiated cells, and tumorigenicity. In the present study, a novel method to differentiate iPS cells into odontoblast-like cells without tumorigenicity using gene transfection was established. It is an important advance in the establishment of efficient methods to generate homogeneous functional odontogenic cells derived from iPS cells. PMID- 26136505 TI - Distinct functional roles of amphibian (Xenopus laevis) colony-stimulating factor 1- and interleukin-34-derived macrophages. AB - Although Mphi represent the most primordial immune cell subsets, the mechanisms governing their functional heterogeneity remain poorly defined. However, it is well established that the CSF-1 cytokine contributes to monopoiesis and to this heterogeneity, whereas the unrelated IL-34 also binds the CSF-1R toward poorly understood immunologic roles. To delineate the molecular and evolutionary basis behind vertebrate Mphi functional heterogeneity, we performed comprehensive transcriptional and functional studies of amphibian (Xenopus laevis) BM (in vitro) and PER (in vivo) Mphi derived by rXlCSF-1 and rXlIL-34. Our findings indicate that these amphibian cytokines promote morphologically and functionally distinct Mphi populations. Mphi induced by rXlCSF-1 possess more robust iNOS gene expression, are substantially more phagocytic, display greater NO responses, and exhibit enhanced bactericidal capacities. By contrast, rXlIL-34-derived Mphi express greater levels of Arg-1 and NADPH oxidase components and possess greater respiratory burst responses. Most notably, whereas CSF-1 Mphi are highly susceptible to the emerging FV3 ranavirus, rXlIL-34 Mphi exhibit potent antiviral activity against this pathogen, which is dependent on reactive oxygen production. This work marks an advance in our understanding of the possible mechanisms governing vertebrate Mphi functional heterogeneity. PMID- 26136506 TI - Natural killer (NK) cells and anti-tumor therapeutic mAb: unexplored interactions. AB - Tumor-targeting mAb are widely used in the treatment of a variety of solid and hematopoietic tumors and represent the first immunotherapeutic approach successfully arrived to the clinic. Nevertheless, the role of distinct immune mechanisms in contributing to their therapeutic efficacy is not completely understood and may vary depending on tumor- or antigen/antibody-dependent characteristics. Availability of next-generation, engineered, tumor-targeting mAb, optimized in their capability to recruit selected immune effectors, re enforces the need for a deeper understanding of the mechanisms underlying anti tumor mAb functionality. NK cells participate with a major role to innate anti tumor responses, by exerting cytotoxic activity and producing a vast array of cytokines. As the CD16 (low-affinity FcgammaRIIIA)-activating receptor is expressed on the majority of NK cells, its effector functions can be ideally recruited against therapeutic mAb-opsonized tumor cells. The exact role of NK cells in determining therapeutic efficacy of tumor-targeting mAb is still unclear and much sought after. This knowledge will be instrumental to design innovative combination schemes with newly validated immunomodulatory agents. We will summarize what is known about the role of NK cells in therapeutic anti-tumor mAb therapy, with particular emphasis on RTX chimeric anti-CD20 mAb, the first one used in clinical practice for treating B cell malignancies. PMID- 26136504 TI - Concise Review: Emerging Role of CD44 in Cancer Stem Cells: A Promising Biomarker and Therapeutic Target. AB - The reception and integration of the plethora of signals a cell receives from its microenvironment determines the cell's fate. CD44 functions as a receptor for hyaluronan and many other extracellular matrix components, as well as a cofactor for growth factors and cytokines, and thus, CD44 is a signaling platform that integrates cellular microenvironmental cues with growth factor and cytokine signals and transduces signals to membrane-associated cytoskeletal proteins or to the nucleus to regulate a variety of gene expression levels related to cell matrix adhesion, cell migration, proliferation, differentiation, and survival. Accumulating evidence indicates that CD44, especially CD44v isoforms, are cancer stem cell (CSC) markers and critical players in regulating the properties of CSCs, including self-renewal, tumor initiation, metastasis, and chemoradioresistance. Furthermore, there is ample evidence that CD44, especially CD44v isoforms, are valuable prognostic markers in various types of tumors. Therefore, therapies that target CD44 may destroy the CSC population, and this holds great promise for the cure of life-threatening cancers. However, many challenges remain to determining how best to use CD44 as a biomarker and therapeutic target. Here we summarize the current findings concerning the critical role of CD44/CD44v in the regulation of cancer stemness and the research status of CD44/CD44v as biomarkers and therapeutic targets in cancer. We also discuss the current challenges and future directions that may lead to the best use of CD44/CD44v for clinical applications. SIGNIFICANCE: Mounting evidence indicates that cancer stem cells (CSCs) are mainly responsible for cancer aggressiveness, drug resistance, and tumor relapse. CD44, especially CD44v isoforms, have been identified as CSC surface markers for isolating and enriching CSCs in different types of cancers. The current findings concerning the critical role of CD44/CD44v in regulation of cancer stemness and the research status of CD44/CD44v as biomarkers and therapeutic targets in cancer are summarized. The current challenges and future directions that may lead to best use of CD44/CD44v for clinical applications are also discussed. PMID- 26136507 TI - High HIV incidence among men who have sex with men attending a community-based voluntary counselling and testing service in Barcelona, Spain: results from the ITACA cohort. AB - OBJECTIVES: To identify the HIV incidence and its associated factors (AFs) of the ITACA, a community-based cohort of HIV-negative men who have sex with men (MSM) established in Barcelona, Spain from 2008 to 2011. METHODS: Participants were men aged 18 years or older, having a negative HIV test result at baseline and agreeing to participate. Bio-behavioural data were collected by peers in each visit. HIV incidence rates using person-time measures and 95% CIs were calculated. Cox logistic regression models were used to identify AFs to seroconversion. RESULTS: Over the period, 3544 participants with at least one follow-up visit or those who had a first visit no longer than a year prior to the date of data censoring were included in the analysis contributing 3567.09 person year (p-y) and 85 MSM seroconverted for an overall HIV incidence of 2.4 per 100 p y (95% CI 1.9 to 2.9) ranging from 1.21/100 (2009) to 3.1/100 p-y (2011). Independent AF included: foreign origin, having more than five HIV tests at baseline, reporting in the preceding 6 months the following: condomless anal sex with the last steady partner of unknown serostatus, more than 10 casual partners, condomless anal sex with casual partner, self-reported gonorrhoea and entered in the cohort in 2010 or 2011. CONCLUSIONS: The ITACA cohort revealed a high and increasing HIV incidence among MSM, especially important among foreign-born men. The findings underscore the need to implement multilevel interventions for MSM taking into account different types of partners, cultural origins and the exposure to other sexually transmitted infections. PMID- 26136508 TI - Diagnostic accuracy of rapid tests for sexually transmitted infections in symptomatic women. AB - OBJECTIVE: To determine the diagnostic accuracy of tests developed for use at the point of care for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and syphilis in women having symptoms of lower urinary tract infection. METHODS: Cross-sectional study involving sexually active 14-49-year-old women with lower urinary tract infection symptoms consulting during 2010 at a private health clinic and at two public hospitals in Bogota, Colombia. Pregnant women, those with a previous hysterectomy or those who received antibiotics during the previous 7 days were excluded. Sequential sampling was used; sample size: 1500 women. The ACON NG and CT duo test combo and the ACON individual test plates for NG and separately for CT were used. The QuickVue Chlamydia rapid test (RT) was also used. All of them were compared with nucleic acid amplification methods. The SD Bioline 3.0 and ACON test for syphilis were evaluated and compared with serological tests. Sensitivity and specificity were estimated. RESULTS: CT RTs had a sensitivity that ranged between 22.7% and 37.7% and specificity between 99.3% and 100%. Sensitivity for NG with ACON Duo was 12.5% and specificity 99.8%. Tests for syphilis had a sensitivity of 91.6-100% and a specificity of 99.7 97.8%. CONCLUSIONS: The RTs studied are not useful for screening for NG at the point of care. In case of CT a recommendation about their use in routine care should be supported by a cost-effectiveness analysis. In screening populations at high risk of sexually transmitted infections or pregnant women, the RTs for syphilis should be used. PMID- 26136509 TI - Drug use moderates associations between location of sex and unprotected anal intercourse in men who have sex with men: nested cross-sectional study of dyadic encounters with new partners. AB - OBJECTIVES: This nested cross-sectional study of dyadic sexual encounters with new male partners reported by men living in England who have sex with men tested moderation between drug use and location of sex in associations with unprotected anal intercourse (UAI). METHODS: Data were drawn from two waves of a longitudinal monthly internet survey of men living in England who have sex with men conducted in 2011. Using generalised estimating equations and logit link, we tested the relationship with UAI of any respondent drug use before sex, specific respondent drug use before sex, location of sex (distinguishing private, sex-on-premises venue and cruising locations) and location-drug use interactions. RESULTS: Any respondent drug use (OR 1.57, 95% CI 1.31 to 1.88) was associated with increased odds of UAI. Relative to encounters in private locations, encounters in sex-on premises venues (0.69, 95% CI 0.52 to 0.91), but not cruising locations, were associated with decreased odds of UAI. Any respondent drug use, respondent use of poppers and respondent use of alcohol were each associated with increased UAI in sex-on-premises venues. DISCUSSION: This analysis presents evidence of moderation between drug use and location of sex in associations with UAI. Though this analysis used a large sample, it relied on community-recruited respondents. Our findings may reflect either 'totalising' effects of drug use across venues or site-specific use of drugs as a mechanism for cognitive escape. Additional qualitative research is necessary to understand these findings in context. PMID- 26136510 TI - The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents. AB - Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings. PMID- 26136512 TI - Usefulness of delta troponin for diagnosis and prognosis assessment of non-ST segment elevation acute chest pain. AB - BACKGROUND: The additional diagnostic and prognostic information provided by delta high-sensitivity troponin T (hs-cTnT) in patients with acute chest pain and hs-cTnT elevation remains unclear. METHODS: The study group consisted of 601 patients presenting at the emergency department with non-ST-segment elevation acute chest pain and hs-cTnT elevation after two determinations (admission and within the first six hours). Maximum hs-cTnT and delta hs-cTnT (absolute or percentage change between the two measurements) were considered. Cutoff values were optimized using the quartile distribution for the endpoints. The endpoints were diagnostic (significant stenosis in the coronary angiogram) and prognostic (death or recurrent myocardial infarction at one year). RESULTS: Regarding the diagnostic endpoint, 114 patients showed a normal angiogram. Both maximum hs-cTnT ?80 ng/ml (OR 2.5, 95% CI 1.3-4.8, P=0.005) and delta hs-cTnT ?20 ng/l (OR 2.1, 95% CI 1.1-4.0, P=0.02) median value cutoffs were related to significant coronary stenosis. Furthermore, the combination of hs-cTn <80 ng/l and delta hs-cTn <20 ng/l showed the lowest probability of significant coronary stenosis (OR 0.3, 95% CI 0.1-0.4, P=0.001). During follow-up, 86 patients experienced the prognostic endpoint. After full adjustment for clinical data, maximum hs-cTnT ?30 ng/l, first quartile cutoff, was related to the outcome (HR 1.8, 95% CI 1.0-3.4, P=0.05), while delta hs-cTnT, either absolute or percentage change, lacked prognostic value. CONCLUSIONS: Maximum hs-cTnT captures all the prognostic information provided by hs-cTnT in non-ST-segment elevation acute chest pain. Low maximum and low delta hs-cTnT are associated with a normal coronary angiogram, which could make the final diagnosis challenging in some cases. PMID- 26136511 TI - Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function. AB - Long-chain acyl-CoA synthetase 1 (ACSL1) contributes more than 90% of total cardiac ACSL activity, but its role in phospholipid synthesis has not been determined. Mice with an inducible knockout of ACSL1 (Acsl1(T-/-)) have impaired cardiac fatty acid oxidation and rely on glucose for ATP production. Because ACSL1 exhibited a strong substrate preference for linoleate, we investigated the composition of heart phospholipids. Acsl1(T-/-) hearts contained 83% less tetralinoleoyl-cardiolipin (CL), the major form present in control hearts. A stable knockdown of ACSL1 in H9c2 rat cardiomyocytes resulted in low incorporation of linoleate into CL and in diminished incorporation of palmitate and oleate into other phospholipids. Overexpression of ACSL1 in H9c2 and HEK-293 cells increased incorporation of linoleate into CL and other phospholipids. To determine whether increasing the content of linoleate in CL would improve mitochondrial respiratory function in Acsl1(T-/-) hearts, control and Acsl1(T-/-) mice were fed a high-linoleate diet; this diet normalized the amount of tetralinoleoyl-CL but did not improve respiratory function. Thus, ACSL1 is required for the normal composition of several phospholipid species in heart. Although ACSL1 determines the acyl-chain composition of heart CL, a high tetralinoleoyl-CL content may not be required for normal function. PMID- 26136513 TI - Expression mechanism of tryptophan hydroxylase 1 in mouse islets during pregnancy. AB - Serotonin signaling plays key roles in augmentation of pancreatic beta-cell function during pregnancy. Increased expression of tryptophan hydroxylase 1 (Tph1), a rate-limiting enzyme for serotonin synthesis by lactogenic hormones, is involved in this phenomenon. To investigate its mechanisms, we here performed 5' RACE and identified beta-cell-specific transcription initiation sites for Tph1. Prolactin enhanced the expression of mRNA containing these exons; however, reporter gene plasmids containing the proximal 5'-flanking region of these exons did not show prolactin responsiveness in MIN6 cells. Prolactin-induced Tph1 expression was inhibited by a Jak2 inhibitor and was partially inhibited by an MEK1/2 or PI3K inhibitor. Therefore, we analyzed interferon gamma-activated sequences (GAS) and found GAS-A about 9-kbp upstream of the transcription start site. The reporter gene plasmid containing the GAS-A region linked to a heterologous promoter showed increased promoter activity by prolactin, which was inhibited by the forced expression of a dominant-negative mutant form of Stat5A and a Jak2 inhibitor. Chromatin immunoprecipitation analysis showed that prolactin treatment augmented Stat5 binding to the GAS-A region in MIN6 cells, as well as in isolated mouse islets, and that Stat5 recognized the GAS-A region in pregnant mouse islets. In addition, the transactivation activity of Stat5 was enhanced by prolactin through the Erk and PI3K pathways in MIN6 cells. Finally, serotonin expression was attenuated in islets of beta-cell-specific Stat5 deficient mice compared with that of control littermates during pregnancy. Our findings suggest that prolactin-induced Tph1 expression is mediated by the activation of Jak2/Stat5, Erk, and PI3K pathways in beta cells. PMID- 26136514 TI - Advances in yeast systematics and phylogeny and their use as predictors of biotechnologically important metabolic pathways. AB - Detection, identification and classification of yeasts have undergone a major transformation in the last decade and a half following application of gene sequence analyses and genome comparisons. Development of a database (barcode) of easily determined DNA sequences from domains 1 and 2 (D1/D2) of the nuclear large subunit rRNA gene and from ITS now permits many laboratories to identify species quickly and accurately, thus replacing the laborious and often inaccurate phenotypic tests previously used. Phylogenetic analysis of gene sequences is leading to a major revision of yeast systematics that will result in redefinition of nearly all genera. This new understanding of species relationships has prompted a change of rules for naming and classifying yeasts and other fungi, and these new rules are presented in the recently implemented International Code of Nomenclature for algae, fungi, and plants (Melbourne Code). The use of molecular methods for species identification and the impact of Code changes on classification will be discussed, as will use of phylogeny for prediction of biotechnological applications. PMID- 26136515 TI - Gene expression analysis using strains constructed by NHEJ-mediated one-step promoter cloning in the yeast Kluyveromyces marxianus. AB - Gene expression analysis provides valuable information to evaluate cellular state. Unlike quantitative mRNA analysis techniques like reverse-transcription PCR and microarray, expression analysis using a reporter gene has not been commonly used for multiple-gene analysis, probably due to the difficulty in preparing multiple reporter-gene constructs. To circumvent this problem, we developed a novel one-step reporter-gene construction system mediated by non homologous end joining (NHEJ) in the yeast Kluyveromyces marxianus. As a selectable reporter gene, the ScURA3 selection marker was fused in frame with a red fluorescent gene yEmRFP (ScURA3:yEmRFP). The N-terminally truncated ScURA3:yEmRFP fragment was prepared by PCR. Promoter sequences were also prepared by PCR using primers containing the sequence of the deleted ScURA3 N-terminus to attach at their 3(') ends. The two DNA fragments were used for the transformation of a ura3(-) strain of K. marxianus, in which two DNA fragments are randomly joined and integrated into the chromosome through NHEJ. Only the correctly aligned fragments produced transformants on uracil-deficient medium and expressed red fluorescence under the control of the introduced promoters. A total of 36 gene promoters involved in glycolysis and other pathways were analyzed. Fluorescence measurements of these strains allowed real-time gene expression analysis in different culture conditions. PMID- 26136516 TI - Progression of mild cognitive impairment to dementia due to AD in clinical settings. AB - OBJECTIVES: To describe the positive predictive value of mild cognitive impairment (MCI) and the factors associated with progression in routine practice. METHODS: A retrospective cohort study was conducted from the French National Alzheimer Database. Among 446,439 patients cared for in the participating centers between January 2009 and January 2014, 45,386 (10.2%) were classified as having MCI and 23,676 had at least one follow-up visit. Annual progression rate was used to describe the progression of patients with MCI to dementia due to Alzheimer disease. Hazard ratios of dementia due to Alzheimer disease were estimated using Cox regression model. RESULTS: Annual progression rate (95% confidence interval) was 13.7% person-years (py) (13.5%-13.9%) with higher rate for amnestic MCI (aMCI) (18.2% py [17.9%-18.5%]) than for nonamnestic MCI (naMCI) (9.5% py [9.3% 9.6%]). Separate regression models were performed for each MCI subtype. Higher education, older age, female sex, and lower Mini-Mental State Examination score were associated with an increased risk of progression for both subtypes. Use of anxiolytics (adjusted hazard ratio [95% confidence interval]: 0.77 [0.66-0.91]) was a protective factor for aMCI whereas antidepressant drugs (1.16 [1.04-1.29]) were associated with an increased risk. For naMCI, prescriptions of antidepressants (0.85 [0.74-0.98]) and antipsychotics (0.55 [0.32-0.93]) were protective for progression. CONCLUSIONS: Under circumstances emulating routine clinical practice, the positive predictive value of an MCI diagnosis is in line with previous clinical studies and the external validity of the concept is strengthened. Distinguishing between aMCI and naMCI is particularly relevant. PMID- 26136517 TI - Neuromyelitis optica in a child with Aicardi-Goutieres syndrome. PMID- 26136518 TI - Mitochondrial DNA sequence variation in multiple sclerosis. AB - OBJECTIVE: To assess the influence of common mitochondrial DNA (mtDNA) sequence variation on multiple sclerosis (MS) risk in cases and controls part of an international consortium. METHODS: We analyzed 115 high-quality mtDNA variants and common haplogroups from a previously published genome-wide association study among 7,391 cases from the International Multiple Sclerosis Genetics Consortium and 14,568 controls from the Wellcome Trust Case Control Consortium 2 project from 7 countries. Significant single nucleotide polymorphism and haplogroup associations were replicated in 3,720 cases and 879 controls from the University of California, San Francisco. RESULTS: An elevated risk of MS was detected among haplogroup JT carriers from 7 pooled clinic sites (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.07-1.24, p = 0.0002) included in the discovery study. The increased risk of MS was observed for both haplogroup T (OR = 1.17, 95% CI = 1.06-1.29, p = 0.002) and haplogroup J carriers (OR = 1.11, 95% CI = 1.01-1.22, p = 0.03). These haplogroup associations with MS were not replicated in the independent sample set. An elevated risk of primary progressive (PP) MS was detected for haplogroup J participants from 3 European discovery populations (OR = 1.49, 95% CI = 1.10-2.01, p = 0.009). This elevated risk was borderline significant in the US replication population (OR = 1.43, 95% CI = 0.99-2.08, p = 0.058) and remained significant in pooled analysis of discovery and replication studies (OR = 1.43, 95% CI = 1.14-1.81, p = 0.002). No common individual mtDNA variants were associated with MS risk. CONCLUSIONS: Identification and validation of mitochondrial genetic variants associated with MS and PPMS may lead to new targets for treatment and diagnostic tests for identifying potential responders to interventions that target mitochondria. PMID- 26136520 TI - Recessive hereditary motor and sensory neuropathy caused by IGHMBP2 gene mutation. PMID- 26136519 TI - ABCD2 score and secondary stroke prevention: meta-analysis and effect per 1,000 patients triaged. AB - OBJECTIVE: Patients with TIA have high risk of recurrent stroke and require rapid assessment and treatment. The ABCD2 clinical risk prediction score is recommended for patient triage by stroke risk, but its ability to stratify by known risk factors and effect on clinic workload are unknown. METHODS: We performed a systematic review and meta-analysis of all studies published between January 2005 and September 2014 that reported proportions of true TIA/minor stroke or mimics, risk factors, and recurrent stroke rates, dichotomized to ABCD2 score =4. We calculated the effect per 1,000 patients triaged on stroke prevention services. RESULTS: Twenty-nine studies, 13,766 TIA patients (range 69-1,679), were relevant: 48% calculated the ABCD2 score retrospectively; few reported on the ABCD2 score's ability to identify TIA mimics or use by nonspecialists. Meta analysis showed that ABCD2 >=4 was sensitive (86.7%, 95% confidence interval [CI] 81.4%-90.7%) but not specific (35.4%, 95% CI 33.3%-37.6%) for recurrent stroke within 7 days. Additionally, 20% of patients with ABCD2 <4 had >50% carotid stenosis or atrial fibrillation (AF); 35%-41% of TIA mimics, and 66% of true TIAs, had ABCD2 score >=4. Among 1,000 patients attending stroke prevention services, including the 45% with mimics, 52% of patients would have an ABCD2 score >=4. CONCLUSION: The ABCD2 score does not reliably discriminate those at low and high risk of early recurrent stroke, identify patients with carotid stenosis or AF needing urgent intervention, or streamline clinic workload. Stroke prevention services need adequate capacity for prompt specialist clinical assessment of all suspected TIA patients for correct patient management. PMID- 26136521 TI - Plasma IP-10 level distinguishes inflammatory myopathy. PMID- 26136522 TI - TIA risk stratification: what an event was and why it happened are more important than a score. PMID- 26136523 TI - A CASQ1 founder mutation in three Italian families with protein aggregate myopathy and hyperCKaemia. AB - BACKGROUND: Protein aggregate myopathies are increasingly recognised conditions characterised by a surplus of endogenous proteins. The molecular and mutational background for many protein aggregate myopathies has been clarified with the discovery of several underlying mutations. Familial idiopathic hyperCKaemia is a benign genetically heterogeneous condition with autosomal dominant features in a high proportion of cases. METHODS: In 10 patients from three Italian families with autosomal dominant benign vacuolar myopathy and hyperCKaemia, we performed linkage analysis and exome sequencing as well as morphological and biochemical investigations. RESULTS AND CONCLUSIONS: We show, by Sanger and exome sequencing, that the protein aggregate myopathy with benign evolution and muscle inclusions composed of excess CASQ1, affecting three Italian families, is due to the D244G heterozygous missense mutation in the CASQ1 gene. Investigation of microsatellite markers revealed a common haplotype in the three families indicating consanguinity and a founder effect. Results from immunocytochemistry, electron microscopy, biochemistry and transfected cell line investigations contribute to our understanding of pathogenetic mechanisms underlining this defect. The mutation is common to other Italian patients and is likely to share a founder effect with them. HyperCKaemia in the CASQ1-related myopathy is common and sometimes the sole overt manifestation. It is likely that CASQ1 mutations may remain undiagnosed if a muscle biopsy is not performed, and the condition could be more common than supposed. PMID- 26136524 TI - Improving diagnostic precision, care and syndrome definitions using comprehensive next-generation sequencing for the inherited bone marrow failure syndromes. AB - BACKGROUND: Phenotypic overlap among the inherited bone marrow failure syndromes (IBMFSs) frequently limits the ability to establish a diagnosis based solely on clinical features. >70 IBMFS genes have been identified, which often renders genetic testing prolonged and costly. Since correct diagnosis, treatment and cancer surveillance often depend on identifying the mutated gene, strategies that enable timely genotyping are essential. METHODS: To overcome these challenges, we developed a next-generation sequencing assay to analyse a panel of 72 known IBMFS genes. Cases fulfilling the clinical diagnostic criteria of an IBMFS but without identified causal genotypes were included. RESULTS: The assay was validated by detecting 52 variants previously found by Sanger sequencing. A total of 158 patients with unknown mutations were studied. Of 75 patients with known IBMFS categories (eg, Fanconi anaemia), 59% had causal mutations. Among 83 patients with unclassified IBMFSs, we found causal mutations and established the diagnosis in 18% of the patients. The assay detected mutant genes that had not previously been reported to be associated with the patient phenotypes. In other cases, the assay led to amendments of diagnoses. In 20% of genotype cases, the results indicated a cancer surveillance programme. CONCLUSIONS: The novel assay is efficient, accurate and has a major impact on patient care. PMID- 26136525 TI - Polytobacco Use of Cigarettes, Cigars, Chewing Tobacco, and Snuff Among US Adults. AB - INTRODUCTION: Tobacco use prevalence has been commonly estimated on a product by product basis and the extent of polytobacco use among current users of each tobacco product is not well understood. This study aimed to examine the prevalence, trends, and correlates of polytobacco use among current users of cigarettes, cigars, chewing tobacco, and snuff in US adults aged >=18. METHODS: We used pooled data from the 1998, 2000, 2005, and 2010 Cancer Control Supplements of the National Health Interview Survey (N = 123 399 adults). Multivariate logistic regression models were estimated to determine significant factors associated with polytobacco use. RESULTS: In 2010, the prevalence of polytobacco use was 8.6% among current cigarette smokers, 50.3% among current cigar users, 54.8% among current chewing tobacco users, and 42.5% among current snuff users. After controlling for other covariates, gender and race/ethnicity did not show consistent associations with poly-use across these four groups of current tobacco users; however, a positive association of young adulthood, less than high school education, and binge drinking with poly-use was consistently found among all these groups. CONCLUSIONS: Polytobacco use is extremely popular among current users of non-cigarette tobacco products. Polytobacco use patterns differ across sociodemographic subpopulations, and the gender and racial/ethnic profiles in poly-users vary across different groups of current tobacco users. Tobacco control strategies need to consider the interrelationships in the use of different tobacco products and the diverse profiles of poly-users in order to develop tailored tobacco prevention and intervention policies to further reduce the burden of tobacco use. PMID- 26136526 TI - Gender Differences in Smoking Behavior and Dependence Motives Among Daily and Nondaily Smokers. AB - INTRODUCTION: While the overall prevalence of smoking has declined, nondaily smoking is on the rise. Among daily smokers (DS) men tend to smoke more cigarettes per day and have higher dependence. Unfortunately little is known about gender differences in nondaily smokers (NDS). METHODS: This secondary-data analysis utilized data from a cross-sectional online survey. Participants reported on smoking behavior (eg, cigarettes per day, history of quit attempts) and nicotine dependence motives as assessed by the Brief Wisconsin Inventory of Dependence Motives via the primary and secondary subscales (ie, core features of tobacco dependence such as craving and accessory motives such as weight control, respectively). RESULTS: Participants were 1175 DS (60% women) and 1201 NDS (56% women). Two interactions between group and gender were noted suggesting that the NDS had greater gender differences in past quit attempts (P < .01) and reported change in smoking behavior over the past year (P < .01). Further, among the NDS group, men scored significantly higher than women on both the primary and secondary dependence motives subscales (3.6+/-0.1 vs. 2.9+/-0.1, P < .0001; 3.8+/ 0.1 vs. 3.3+/-0.1, P < .0001; respectively). There were no significant differences in dependence motives in the DS group (P > .05). CONCLUSIONS: Gender differences in smoking behavior and dependence motives varied between NDS and DS. Specifically, gender differences in smoking behavior and smoking dependence motives may be larger among NDS compared to DS. Additional research is needed to explore how these relationships may relate to smoking cessation in NDS. PMID- 26136528 TI - NAD(P)H quinone oxidoreductase1 regulates neutrophil elastase-induced mucous cell metaplasia. Am JPhysiol Lung Cell Mol Physiol 303: L181-L188, 2012; doi:10.1152/ajplung.00084.2012. PMID- 26136527 TI - Neutrophil elastase-induced elastin degradation mediates macrophage influx and lung injury in 60% O2-exposed neonatal rats. AB - Neutrophil (PMNL) influx precedes lung macrophage (LM) influx into the lung following exposure of newborn pups to 60% O2. We hypothesized that PMNL were responsible for the signals leading to LM influx. This was confirmed when inhibition of PMNL influx with a CXC chemokine receptor-2 antagonist, SB-265610, also prevented the 60% O2-dependent LM influx, LM-derived nitrotyrosine formation, and pruning of small arterioles. Exposure to 60% O2 was associated with increased lung contents of neutrophil elastase and alpha-elastin, a marker of denatured elastin, and a decrease in elastin fiber density. This led us to speculate that neutrophil elastase-induced elastin fragments were the chemokines that led to a LM influx into the 60% O2-exposed lung. Inhibition of neutrophil elastase with sivelestat or elafin attenuated the LM influx. Sivelestat also attenuated the 60% O2-induced decrease in elastin fiber density. Daily injections of pups with an antibody to alpha-elastin prevented the 60% O2-dependent LM influx, impaired alveologenesis, and impaired small vessel formation. This suggests that neutrophil elastase inhibitors may protect against neonatal lung injury not only by preventing structural elastin degradation, but also by blocking elastin fragment-induced LM influx, thus preventing tissue injury from LM-derived peroxynitrite formation. PMID- 26136529 TI - Pro-B-type natriuretic peptide is cleaved intracellularly: impact of distance between O-glycosylation and cleavage sites. AB - We investigated the molecular mechanism underlying the processing of pro-B-type natriuretic peptide (proBNP). Rat neonatal atrial and ventricular myocytes were cultured separately. We examined the molecular forms of secreted and intracellular BNP in atrial and ventricular myocytes; levels of corin and furin mRNA in atrial and ventricular myocytes; the effect their knockdown on proBNP processing; plasma molecular forms of BNP from rats and humans with and without heart failure; and the impact of the distance between the glycosylation and cleavage sites in wild-type and mutant human proBNP, expressed in rat myocytes transfected with lentiviral vectors. BNP was the major molecular form secreted by atrial and ventricular myocytes. Transfection of furin siRNA reduced proBNP processing in both atrial and ventricular myocytes; however, transfection of corin siRNA did not reduce it. BNP was the major molecular form in rat plasma, whereas proBNP was the major form in human plasma. The relative fraction of human BNP in rat myocytes expressing human proBNP was about 60%, but increasing the distance between the glycosylation and cleavage sites through mutation, increased the processed fraction correspondingly. These results suggest that proBNP is processed into BNP intracellularly by furin. The level of proBNP processing is lower in humans than rats, most likely due to the smaller distance between the O glycosylation and cleavage sites in humans. PMID- 26136530 TI - Limb suction evoked during arterial occlusion causes systemic sympathetic activity in humans. AB - Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We hypothesized that the application of suction to the human limbs would activate this venous distension reflex and raise sympathetic outflow. We placed airtight pressure tanks and applied 100 mmHg negative pressure to an arterially occluded limb (occlusion and suction, O&S) to induce tissue deformation without fluid translocation. BP, heart rate (HR), and MSNA were assessed in 19 healthy subjects during 2 min of arm or leg O&S. Occlusion without suction served as a control. During a separate visit, saline (5% forearm volume) was infused into veins of the arterially occluded arm (n = 13). The O&S increased limb circumference, MSNA burst rate (arm: Delta6.7 +/- 0.7; leg: Delta6.8 +/- 0.7 bursts/min), and total activity (arm: Delta199 +/- 14; leg: Delta172 +/- 22 units/min) and BP (arm: Delta4.3 +/- 0.3; leg: Delta9.4 +/- 1.4 mmHg) from the baseline. The MSNA and BP responses during arm O&S correlated with those during leg O&S. Occlusion alone had no effect on MSNA and BP. MSNA (r = 0.607) responses during arm O&S correlated with those evoked by the saline infusion into the arm. These correlations suggest that sympathetic activation during limb O&S is likely, at least partially, to be evoked via the venous distension reflex. These data suggest that suction of an occluded limb evokes sympathetic activation and that the limb venous distension reflex exists in arms and legs of normal humans. PMID- 26136531 TI - The role of efferent cholinergic transmission for the insulinotropic and glucagonostatic effects of GLP-1. AB - The importance of vagal efferent signaling for the insulinotropic and glucagonostatic effects of glucagon-like peptide-1 (GLP-1) was investigated in a randomized single-blinded study. Healthy male participants (n = 10) received atropine to block vagal cholinergic transmission or saline infusions on separate occasions. At t = 15 min, plasma glucose was clamped at 6 mmol/l. GLP-1 was infused at a low dose (0.3 pmol.kg(-1).min(-1)) from t = 45-95 min and at a higher dose (1 pmol.kg(-1).min(-1)) from t = 95-145 min. Atropine blocked muscarinic, cholinergic transmission, as evidenced by an increase in heart rate [peak: 70 +/- 2 (saline) vs. 90 +/- 2 (atropine) beats/min, P < 0.002] and suppression of pancreatic polypeptide levels [area under the curve during the GLP 1 infusions (AUC45-145): 492 +/- 85 (saline) vs. 247 +/- 59 (atropine) pmol/l * min, P < 0.0001]. More glucose was needed to maintain the clamp during the high dose GLP-1 infusion steady-state period on the atropine day [6.4 +/- 0.9 (saline) vs. 8.7 +/- 0.8 (atropine) mg.kg(-1).min(-1), P < 0.0023]. GLP-1 dose-dependently increased insulin secretion on both days. The insulinotropic effect of GLP-1 was not impaired by atropine [C-peptide AUCs45-145: 99 +/- 8 (saline) vs. 113 +/- 13 (atropine) nmol/l * min, P = 0.19]. Atropine suppressed glucagon levels additively with GLP-1 [AUC45-145: 469 +/- 70 (saline) vs. 265 +/- 50 (atropine) pmol/l * min, P = 0.018], resulting in hypoglycemia when infusions were suspended [3.6 +/- 0.2 (saline) vs. 2.7 +/- 0.2 (atropine) mmol/l, P < 0.0001]. To ascertain whether atropine could independently suppress glucagon levels, control experiments (n = 5) were carried out without GLP-1 infusions [AUC45-145: 558 +/- 103 (saline) vs. 382 +/- 76 (atropine) pmol/l * min, P = 0.06]. Our results suggest that efferent muscarinic activity is not required for the insulinotropic effect of exogenous GLP-1 but that blocking efferent muscarinic activity independently suppresses glucagon secretion. In combination, GLP-1 and muscarinic blockade strongly affect glucose turnover. PMID- 26136532 TI - Renal mineralocorticoid receptor and electrolyte homeostasis. AB - The renal mineralocorticoid receptor (MR) is a steroid hormone receptor essential for maintaining electrolyte homeostasis. Its role in mediating effects of aldosterone was likely vital in enabling the evolution of terrestrial life. Dysregulated aldosterone-MR signaling has been identified as the cause of multiple clinical diseases, suggesting the physiological importance of the MR. While the physiology of this pathway has been studied for over 60 years, only more recently have genetic mouse models been available to dissect its function in vivo. This review will focus on recent advances in our knowledge of MR function with an emphasis on these models. PMID- 26136533 TI - Obesity-associated cardiac dysfunction in starvation-selected Drosophila melanogaster. AB - There is a clear link between obesity and cardiovascular disease, but the complexity of this interaction in mammals makes it difficult to study. Among the animal models used to investigate obesity-associated diseases, Drosophila melanogaster has emerged as an important platform of discovery. In the laboratory, Drosophila can be made obese through lipogenic diets, genetic manipulations, and adaptation to evolutionary stress. While dietary and genetic changes that cause obesity in flies have been demonstrated to induce heart dysfunction, there have been no reports investigating how obesity affects the heart in laboratory-evolved populations. Here, we studied replicated populations of Drosophila that had been selected for starvation resistance for over 65 generations. These populations evolved characteristics that closely resemble hallmarks of metabolic syndrome in mammals. We demonstrate that starvation selected Drosophila have dilated hearts with impaired contractility. This phenotype appears to be correlated with large fat deposits along the dorsal cuticle, which alter the anatomical position of the heart. We demonstrate a strong relationship between fat storage and heart dysfunction, as dilation and reduced contractility can be rescued through prolonged fasting. Unlike other Drosophila obesity models, the starvation-selected lines do not exhibit excessive intracellular lipid deposition within the myocardium and rather store excess triglycerides in large lipid droplets within the fat body. Our findings provide a new model to investigate obesity-associated heart dysfunction. PMID- 26136534 TI - Modulation of autophagy signaling with resistance exercise and protein ingestion following short-term energy deficit. AB - Autophagy contributes to remodeling of skeletal muscle and is sensitive to contractile activity and prevailing energy availability. We investigated changes in targeted genes and proteins with roles in autophagy following 5 days of energy balance (EB), energy deficit (ED), and resistance exercise (REX) after ED. Muscle biopsies from 15 subjects (8 males, 7 females) were taken at rest following 5 days of EB [45 kcal.kg fat free mass (FFM)(-1).day(-1)] and 5 days of ED (30 kcal.kg FFM(-1).day(-1)). After ED, subjects completed a bout of REX and consumed either placebo (PLA) or 30 g whey protein (PRO) immediately postexercise. Muscle biopsies were obtained at 1 and 4 h into recovery in each trial. Resting protein levels of autophagy-related gene protein 5 (Atg5) decreased after ED compared with EB (~23%, P < 0.001) and remained below EB from 1 to 4 h postexercise in PLA (~17%) and at 1 h in PRO (~18%, P < 0.05). In addition, conjugated Atg5 (cAtg12) decreased below EB in PLA at 4 h (~20, P < 0.05); however, its values were increased above this time point in PRO at 4 h alongside increases in FOXO1 above EB (~22-26%, P < 0.05). Notably, these changes were subsequent to increases in unc-51-like kinase 1(Ser757) phosphorylation (~60%) 1 h postexercise in PRO. No significant changes in gene expression of selected autophagy markers were found, but EGR-1 increased above ED and EB in PLA (~417-864%) and PRO (~1,417-2,731%) trials 1 h postexercise (P < 0.001). Postexercise protein availability, compared with placebo, can selectively promote autophagic responses to REX in ED. PMID- 26136535 TI - Dopamine, vesicular transporters, and dopamine receptor expression in rat major salivary glands. AB - The localization of dopamine stores and the expression and localization of dopamine (DAT) and vesicular monoamine transporters (VMAT) type-1 and -2 and of dopamine D1-like and D2-like receptor subtypes were investigated in rat submandibular, sublingual, and parotid salivary glands by HPLC with electrochemical detection, as well as immunochemical and immunohistochemical techniques. Male Wistar rats of 2 mo of age were used. The highest dopamine levels were measured in the parotid gland, followed by the submandibular and sublingual glands. Western blot analysis revealed DAT, VMAT-1, VMAT-2, and dopamine receptors immunoreactivity in membrane preparations obtained from the three glands investigated. Immunostaining for dopamine and transporters was developed within striated ducts. Salivary glands processed for dopamine receptors immunohistochemistry developed an immunoreaction primarily in striated and excretory ducts. In the submandibular gland, acinar cells displayed strong immunoreactivity for the D2 receptor, while cells of the convoluted granular tubules were negative for both D1-like and D2-like receptors. Parotid glands acinar cells displayed the highest immunoreactivity for both D1 and D2 receptors compared with other salivary glands. The above localization of dopamine and dopaminergic markers investigated did not correspond closely with neuron-specific enolase (NSE) localization. This indicates that at least in part, catecholamine stores and dopaminergic markers are independent from glandular innervation. These findings suggest that rat major salivary glands express a dopaminergic system probably involved in salivary secretion. The stronger immunoreactivity for dopamine transporters and receptors in striated duct cells suggests that the dopaminergic system could regulate not only quality, but also volume and ionic concentration of saliva. PMID- 26136536 TI - A World Perspective. Promoting Physiology Research in Africa: Leveraging Pockets of Excellence. PMID- 26136537 TI - Undergraduate Physiology Degree Programs in the United States: from Famine to Feast. PMID- 26136538 TI - Anatomy of a Physiology Major. PMID- 26136539 TI - Adapt or Perish. PMID- 26136540 TI - The Evolution of Unidirectional Pulmonary Airflow. AB - Conventional wisdom holds that the avian respiratory system is unique because air flows in the same direction through most of the gas-exchange tubules during both phases of ventilation. However, recent studies showing that unidirectional airflow also exists in crocodilians and lizards raise questions about the true phylogenetic distribution of unidirectional airflow, the selective drivers of the trait, the date of origin, and the functional consequences of this phenomenon. These discoveries suggest unidirectional flow was present in the common diapsid ancestor and are inconsistent with the traditional paradigm that unidirectional flow is an adaptation for supporting high rates of gas exchange. Instead, these discoveries suggest it may serve functions such as decreasing the work of breathing, decreasing evaporative respiratory water loss, reducing rates of heat loss, and facilitating crypsis. The divergence in the design of the respiratory system between unidirectionally ventilated lungs and tidally ventilated lungs, such as those found in mammals, is very old, with a minimum date for the divergence in the Permian Period. From this foundation, the avian and mammalian lineages evolved very different respiratory systems. I suggest the difference in design is due to the same selective pressure, expanded aerobic capacity, acting under different environmental conditions. High levels of atmospheric oxygen of the Permian Period relaxed selection for a thin blood-gas barrier and may have resulted in the homogeneous, broncho-alveolar design, whereas the reduced oxygen of the Mesozoic selected for a heterogeneous lung with an extremely thin blood gas barrier. These differences in lung design may explain the puzzling pattern of ecomorphological diversification of Mesozoic mammals: all were small animals that did not occupy niches requiring a great aerobic capacity. The broncho-alveolar lung and the hypoxia of the Mesozoic may have restricted these mammals from exploiting niches of large body size, where cursorial locomotion can be advantageous, as well as other niches requiring great aerobic capacities, such as those using flapping flight. Furthermore, hypoxia may have exerted positive selection for a parasagittal posture, the diaphragm, and reduced erythrocyte size, innovations that enabled increased rates of ventilation and more rapid rates of diffusion in the lung. PMID- 26136541 TI - The Hibernation Continuum: Physiological and Molecular Aspects of Metabolic Plasticity in Mammals. AB - Mammals are often considered to be masters of homeostasis, with the ability to maintain a constant internal milieu, despite marked changes in the environment; however, many species exhibit striking physiological and biochemical plasticity in the face of environmental fluctuations. Here, we review metabolic depression and body temperature fluctuation in mammals, with a focus on the extreme example of hibernation in small-bodied eutherian species. Careful exploitation of the phenotypic plasticity of mammals with metabolic flexibility may provide the key to unlocking the molecular secrets of orchestrating and surviving reversible metabolic depression in less plastic species, including humans. PMID- 26136542 TI - Performance Enhancement: What Are the Physiological Limits? AB - Our objective is to highlight some key physiological determinants of endurance exercise performance and to discuss how these can be further improved. Vo2max remains remarkably stable throughout an athletic career. By contrast, exercise economy, lactate threshold, and critical power may be improved in world-class athletes by specific exercise training regimes and/or with more years of training. PMID- 26136545 TI - Calcium Sensing in the Renal Tubule. AB - In addition to its prominent role in the parathyroid gland, the calcium-sensing receptor (CaSR) is expressed in various tissues, including the kidney. This article reviews current data on the calcium-sensing properties of the kidney, the localization of the CaSR protein along the nephron, and its function in calcium homeostasis and in hypercalciuria. PMID- 26136543 TI - Putting the Squeeze on Airway Epithelia. AB - Asthma is characterized by chronic inflammation, airway hyperresponsiveness, and progressive airway remodeling. The airway epithelium is known to play a critical role in the initiation and perpetuation of these processes. Here, we review how excessive epithelial stress generated by bronchoconstriction is sufficient to induce airway remodeling, even in the absence of inflammatory cells. PMID- 26136546 TI - The Physiology of Proinsulin C-Peptide: Unanswered Questions and a Proposed Model. AB - C-peptide is produced, processed, and secreted with insulin, and appears to exert separate but intimately related effects. In this review, we address the existence of the C-peptide receptor, the interaction between C-peptide and insulin, and the potential physiological significance of proinsulin C-peptide. PMID- 26136544 TI - Humans In Hypoxia: A Conspiracy Of Maladaptation?! AB - We address adaptive vs. maladaptive responses to hypoxemia in healthy humans and hypoxic-tolerant species during wakefulness, sleep, and exercise. Types of hypoxemia discussed include short-term and life-long residence at high altitudes, the intermittent hypoxemia attending sleep apnea, or training regimens prescribed for endurance athletes. We propose that hypoxia presents an insult to O2 transport, which is poorly tolerated in most humans because of the physiological cost. PMID- 26136547 TI - Smoking - Does It Affect Rheumatoid Arthritis Activity? Does It Matter? PMID- 26136548 TI - Common Design and Analysis Issues in Clinical Trials. PMID- 26136549 TI - Does Viral Hemorrhagic Fever Represent Reactive Hemophagocytic Syndrome? PMID- 26136550 TI - Sustained Remission: An Unmet Need in Patients with Giant-cell Arteritis. PMID- 26136551 TI - Severe Tophaceous Gout with Radiograph Examination of Diffused Calcified Soft Tissue Tophi. PMID- 26136552 TI - A Big Toe in the Ear? Two Cases of Gouty Tophi Located in the Temporomandibular Joint. PMID- 26136553 TI - Possible Implication of Red Blood Cells in the Prothrombotic Risk in Early Rheumatoid Arthritis. PMID- 26136554 TI - Case Report and Literature Review: Quinacrine-induced Cholestatic Hepatitis in Undifferentiated Connective Tissue Disease. PMID- 26136555 TI - Physiological role of NBCe2 in the regulation of electrolyte transport in the distal nephron. AB - The electrogenic Na(+)-HCO3 (-) cotransporter 2 (NBCe2) is a newly discovered protein in the distal nephron. Our understanding is minimal regarding its physiological role in renal electrolyte transport. In this mini-review, we summarize the potential function of NBCe2 in the regulation of blood pressure, acid-base, and K(+) and Ca(2+) transport in the distal nephron. PMID- 26136556 TI - Rho GAP myosin IXa is a regulator of kidney tubule function. AB - Mammalian class IX myosin Myo9a is a single-headed, actin-dependent motor protein with Rho GTPase-activating protein activity that negatively regulates Rho GTPase signaling. Myo9a is abundantly expressed in ciliated epithelial cells of several organs. In mice, genetic deletion of Myo9a leads to the formation of hydrocephalus. Whether Myo9a also has essential functions in the epithelia of other organs of the body has not been explored. In the present study, we report that Myo9a-deficient mice develop bilateral renal disease, characterized by dilation of proximal tubules, calyceal dilation, and thinning of the parenchyma and fibrosis. These structural changes are accompanied by polyuria (with normal vasopressin levels) and low-molecular-weight proteinuria. Immunohistochemistry revealed that Myo9a is localized to the circumferential F-actin belt of proximal tubule cells. In kidneys lacking Myo9a, the multiligand binding receptor megalin and its ligand albumin accumulated at the luminal surface of Myo9a-deficient proximal tubular cells, suggesting that endocytosis is dysregulated. In addition, we found, surprisingly, that levels of murine diaphanous-related formin-1, a Rho effector, were decreased in Myo9a-deficient kidneys as well as in Myo9a knockdown LLC-PK1 cells. In summary, deletion of the Rho GTPase-activating protein Myo9a in mice causes proximal tubular dilation and fibrosis, and we speculate that downregulation of murine diaphanous-related formin-1 and impaired protein reabsorption contribute to the pathophysiology. PMID- 26136557 TI - ABCG2: the molecular mechanisms of urate secretion and gout. AB - The human propensity for high levels of serum uric acid (SUA) is a trait that has defied explanation. Is it beneficial? Is it pathogenic? Its role in the human diseases like gout and kidney stones was discovered over a century ago [Richette P, Bardin T. Lancet 375: 318-328, 2010; Rivard C, Thomas J, Lanaspa MA, Johnson RJ. Rheumatology (Oxford) 52: 421-426, 2013], but today emerging new genetic and epidemiological techniques have revived an age-old debate over whether high uric acid levels (hyperuricemia) independently increase risk for diseases like hypertension and chronic kidney disease [Feig DI. J Clin Hypertens (Greenwich) 14: 346-352, 2012; Feig DI, Madero M, Jalal DI, Sanchez-Lozada LG, Johnson RJ. J Pediatr 162: 896-902, 2013; Feig DI, Soletsky B, Johnson RJ. JAMA 300: 924-932, 2008; Wang J, Qin T, Chen J, Li Y, Wang L, Huang H, Li J. PLoS One 9: e114259, 2014; Zhu P, Liu Y, Han L, Xu G, Ran JM. PLoS One 9: e100801, 2014]. Part of the mystery of the role uric acid plays in human health stems from our lack of understanding of how humans regulate uric acid homeostasis, an understanding that could shed light on the historic role of uric acid in human adaptation and its present role in human pathogenesis. This review will highlight the recent work to identify the first important human uric acid secretory transporter, ABCG2, and the identification of a common causal ABCG2 variant, Q141K, for hyperuricemia and gout. PMID- 26136558 TI - H2O2 generated by NADPH oxidase 4 contributes to transient receptor potential vanilloid 1 channel-mediated mechanosensation in the rat kidney. AB - The presence of NADPH oxidase (Nox) in the kidney, especially Nox4, results in H2O2 production, which regulates Na(+) excretion and urine formation. Redox sensitive transient receptor potential vanilloid 1 channels (TRPV1s) are distributed in mechanosensory fibers of the renal pelvis and monitor changes in intrapelvic pressure (IPP) during urine formation. The present study tested whether H2O2 derived from Nox4 affects TRPV1 function in renal sensory responses. Perfusion of H2O2 into the renal pelvis dose dependently increased afferent renal nerve activity and substance P (SP) release. These responses were attenuated by cotreatment with catalase or TRPV1 blockers. In single unit recordings, H2O2 activated afferent renal nerve activity in response to rising IPP but not high salt. Western blots revealed that Nox2 (gp91(phox)) and Nox4 are both present in the rat kidney, but Nox4 is abundant in the renal pelvis and originates from dorsal root ganglia. This distribution was associated with expression of the Nox4 regulators p22(phox) and polymerase delta-interacting protein 2. Coimmunoprecipitation experiments showed that IPP increases polymerase delta interacting protein 2 association with Nox4 or p22(phox) in the renal pelvis. Interestingly, immunofluorescence labeling demonstrated that Nox4 colocalizes with TRPV1 in sensory fibers of the renal pelvis, indicating that H2O2 generated from Nox4 may affect TRPV1 activity. Stepwise increases in IPP and saline loading resulted in H2O2 and SP release, sensory activation, diuresis, and natriuresis. These effects, however, were remarkably attenuated by Nox inhibition. Overall, these results suggest that Nox4-positive fibers liberate H2O2 after mechanostimulation, thereby contributing to a renal sensory nerve-mediated diuretic/natriuretic response. PMID- 26136559 TI - Interactions between HIF-1alpha and AMPK in the regulation of cellular hypoxia adaptation in chronic kidney disease. AB - Renal hypoxia contributes to chronic kidney disease (CKD) progression, as validated in experimental and human CKD. In the early stages, increased oxygen consumption causes oxygen demand/supply mismatch, leading to hypoxia. Hence, early targeting of the determinants and regulators of oxygen consumption in CKD may alter the disease course before permanent damage ensues. Here, we focus on hypoxia inducible factor-1alpha (HIF-1alpha) and AMP-activated protein kinase (AMPK) and on the mechanisms by which they may facilitate cellular hypoxia adaptation. We found that HIF-1alpha activation in the subtotal nephrectomy (STN) model of CKD limits protein synthesis, inhibits apoptosis, and activates autophagy, presumably for improved cell survival. AMPK activation was diminished in the STN kidney and was remarkably restored by HIF-1alpha activation, demonstrating a novel role for HIF-1alpha in the regulation of AMPK activity. We also investigated the independent and combined effects of HIF-1alpha and AMPK on cell survival and death pathways by utilizing pharmacological and knockdown approaches in cell culture models. We found that the effect of HIF-1alpha activation on autophagy is independent of AMPK, but on apoptosis it is partially AMPK dependent. The effects of HIF-1alpha and AMPK activation on inhibiting protein synthesis via the mTOR pathway appear to be additive. These various effects were also observed under hypoxic conditions. In conclusion, HIF-1alpha and AMPK appear to be linked at a molecular level and may act as components of a concerted cellular response to hypoxic stress in the pathophysiology of CKD. PMID- 26136561 TI - Implant failure in a proximal femoral fracture treated with dynamic hip screw fixation. AB - Dynamic hip screw fixation is a common orthopaedic procedure and to date, still can cause difficulties to the senior trauma surgeon. We present a case where an extra-capsular fracture of the proximal femur was managed with a dynamic hip screw (DHS) fixation. She proceeded to the operating theatre, where the fracture was stabilized with a 75-mm DHS and short-barrelled plate. The implant position was checked with intraoperative screening and the position accepted. Following attempted mobilization at 11 days post-operatively, the patient developed a recurrence of her preoperative pain. X-ray showed that the implant screw had separated from the barrel. Later scrutiny of the intraoperative screening films revealed that the barrel and screw were not engaged at the time of surgery. Intraoperative screening films should be carefully checked to ensure congruity of implant components. PMID- 26136560 TI - Calmodulin and CaMKII modulate ENaC activity by regulating the association of MARCKS and the cytoskeleton with the apical membrane. AB - Phosphatidylinositol bisphosphate (PIP2) regulates epithelial sodium channel (ENaC) open probability. In turn, myristoylated alanine-rich C kinase substrate (MARCKS) protein or MARCKS-like protein 1 (MLP-1) at the plasma membrane regulates the delivery of PIP2 to ENaC. MARCKS and MLP-1 are regulated by changes in cytosolic calcium; increasing calcium promotes dissociation of MARCKS from the membrane, but the calcium-regulatory mechanisms are unclear. However, it is known that increased intracellular calcium can activate calmodulin and we show that inhibition of calmodulin with calmidazolium increases ENaC activity presumably by regulating MARCKS and MLP-1. Activated calmodulin can regulate MARCKS and MLP-1 in two ways. Calmodulin can bind to the effector domain of MARCKS or MLP-1, inactivating both proteins by causing their dissociation from the membrane. Mutations in MARCKS that prevent calmodulin association prevent dissociation of MARCKS from the membrane. Calmodulin also activates CaM kinase II (CaMKII). An inhibitor of CaMKII (KN93) increases ENaC activity, MARCKS association with ENaC, and promotes MARCKS movement to a membrane fraction. CaMKII phosphorylates filamin. Filamin is an essential component of the cytoskeleton and promotes association of ENaC, MARCKS, and MLP-1. Disruption of the cytoskeleton with cytochalasin E reduces ENaC activity. CaMKII phosphorylation of filamin disrupts the cytoskeleton and the association of MARCKS, MLP-1, and ENaC, thereby reducing ENaC open probability. Taken together, these findings suggest calmodulin and CaMKII modulate ENaC activity by destabilizing the association between the actin cytoskeleton, ENaC, and MARCKS, or MLP-1 at the apical membrane. PMID- 26136562 TI - Primary orbital Ewing's sarcoma presenting with local recurrence to maxillary sinus shortly after tumor resection. AB - Ewing's sarcoma (ES) is a malignant, small-round-cell neoplasm that normally affects the long bones of the limbs or the pelvis. Primary orbital ES of the skull has been considered extremely rare. We describe the case of a 19-year-old female patient with primary ES originating from the inferior orbital rime and, shortly after tumor resection, local recurrence to the maxillary sinus. PMID- 26136563 TI - We count but should we scrutinize? An unreported complication in spinal surgery. AB - Complications following spinal surgery can range from simple wound infection to complete paralysis. Intraoperative checks have been introduced to account for all the instruments and materials used and help minimize surgeon-related complications. We report a case of a broken osteotome tip within the spinal canal following a routine posterior decompression of the lumbar spine. PMID- 26136564 TI - An Aptamer against the Matrix Binding Domain on the Hepatitis B Virus Capsid Impairs Virion Formation. AB - The hepatitis B virus (HBV) particle is an icosahedral nucleocapsid surrounded by a lipid envelope containing viral surface proteins. A small domain (matrix domain [MD]) in the large surface protein L and a narrow region (matrix binding domain [MBD]) including isoleucine 126 on the capsid surface have been mapped, in which point mutations such as core I126A specifically blocked nucleocapsid envelopment. It is possible that the two domains interact with each other during virion morphogenesis. By the systematic evolution of ligands by exponential enrichment (SELEX) method, we evolved DNA aptamers from an oligonucleotide library binding to purified recombinant capsids but not binding to the corresponding I126A mutant capsids. Aptamers bound to capsids were separated from unbound molecules by filtration. After 13 rounds of selections and amplifications, 16 different aptamers were found among 73 clones. The four most frequent aptamers represented more than 50% of the clones. The main aptamer, AO-01 (13 clones, 18%), showed the lowest dissociation constant (Kd) of 180 +/- 82 nM for capsid binding among the four molecules. Its Kd for I126A capsids was 1,306 +/- 503 nM. Cotransfection of Huh7 cells with AO-01 and an HBV genomic construct resulted in 47% inhibition of virion production at 3 days posttransfection, but there was no inhibition by cotransfection of an aptamer with a random sequence. The half-life of AO-01 in cells was 2 h, which might explain the incomplete inhibition. The results support the importance of the MBD for nucleocapsid envelopment. Inhibiting the MD-MBD interaction with a low-molecular-weight substance might represent a new approach for an antiviral therapy. IMPORTANCE: Approximately 240 million people are persistently infected with HBV. To date, antiviral therapies depend on a single target, the viral reverse transcriptase. Future additional targets could be viral protein-protein interactions. We selected a 55-base-long single-stranded DNA molecule (aptamer) which binds with relatively high affinity to a region on the HBV capsid interacting with viral envelope proteins during budding. This aptamer inhibits virion formation in cell culture. The results substantiate the current model for HBV morphogenesis and show that the capsid envelope interaction is a potential antiviral target. PMID- 26136565 TI - Double-Stranded RNA Is Detected by Immunofluorescence Analysis in RNA and DNA Virus Infections, Including Those by Negative-Stranded RNA Viruses. AB - Early biochemical studies of viral replication suggested that most viruses produce double-stranded RNA (dsRNA), which is essential for the induction of the host immune response. However, it was reported in 2006 that dsRNA could be detected by immunofluorescence antibody staining in double-stranded DNA and positive-strand RNA virus infections but not in negative-strand RNA virus infections. Other reports in the literature seemed to support these observations. This suggested that negative-strand RNA viruses produce little, if any, dsRNA or that more efficient viral countermeasures to mask dsRNA are mounted. Because of our interest in the use of dsRNA antibodies for virus discovery, particularly in pathological specimens, we wanted to determine how universal immunostaining for dsRNA might be in animal virus infections. We have detected the in situ formation of dsRNA in cells infected with vesicular stomatitis virus, measles virus, influenza A virus, and Nyamanini virus, which represent viruses from different negative-strand RNA virus families. dsRNA was also detected in cells infected with lymphocytic choriomeningitis virus, an ambisense RNA virus, and minute virus of mice (MVM), a single-stranded DNA (ssDNA) parvovirus, but not hepatitis B virus. Although dsRNA staining was primarily observed in the cytoplasm, it was also seen in the nucleus of cells infected with influenza A virus, Nyamanini virus, and MVM. Thus, it is likely that most animal virus infections produce dsRNA species that can be detected by immunofluorescence staining. The apoptosis induced in several uninfected cell lines failed to upregulate dsRNA formation. IMPORTANCE: An effective antiviral host immune response depends on recognition of viral invasion and an intact innate immune system as a first line of defense. Double-stranded RNA (dsRNA) is a viral product essential for the induction of innate immunity, leading to the production of type I interferons (IFNs) and the activation of hundreds of IFN-stimulated genes. The present study demonstrates that infections, including those by ssDNA viruses and positive- and negative strand RNA viruses, produce dsRNAs detectable by standard immunofluorescence staining. While dsRNA staining was primarily observed in the cytoplasm, nuclear staining was also present in some RNA and DNA virus infections. The nucleus is unlikely to have pathogen-associated molecular pattern (PAMP) receptors for dsRNA because of the presence of host dsRNA molecules. Thus, it is likely that most animal virus infections produce dsRNA species detectable by immunofluorescence staining, which may prove useful in viral discovery as well. PMID- 26136566 TI - HIV-1 Cell-Free and Cell-to-Cell Infections Are Differentially Regulated by Distinct Determinants in the Env gp41 Cytoplasmic Tail. AB - The HIV-1 envelope (Env) glycoprotein mediates viral entry during both cell-free and cell-to-cell infection of CD4(+) T cells. The highly conserved long cytoplasmic tail (CT) of Env is required in a cell type-dependent manner for optimal infectivity of cell-free virus. To probe the role of the CT in cell-to cell infection, we tested a panel of mutations in the CT region that maintain or attenuate cell-free infection to investigate whether the functions of the CT are conserved during cell-free and cell-to-cell infection. The mutations tested included truncations of structural motifs in the gp41 CT and two point mutations in lentiviral lytic peptide 3 (LLP-3) previously described as disrupting the infectivity of cell-free virus. We found that small truncations of 28 to 43 amino acids (aa) or two LLP-3 point mutations, YW_SL and LL_RQ, severely impaired single-round cell-free infectivity 10-fold or more relative to wild-type full length CT. These mutants showed a modest 2-fold reduction in cell-to-cell infection assays. Conversely, large truncations of 93 to 124 aa severely impaired cell-to-cell infectivity 20-fold or more while resulting in a 50% increase in infectivity of cell-free viral particles when produced in 293T cells. Intermediate truncations of 46 to 90 aa showed profound impairment of both modes of infection. Our results show that the abilities of Env to support cell-free and cell-to-cell infection are genetically distinct. These differences are cell type dependent for large-CT-truncation mutants. Additionally, point mutants in LLP-3 can maintain multiround propagation from cell-to-cell in primary CD4(+) T cells. IMPORTANCE: The functions of HIV Env gp41 CT remain poorly understood despite being widely studied in the context of cell-free infection. We have identified domains of the gp41 CT responsible for striking selective deficiencies in either cell-free or cell-to-cell infectivity. These differences may reflect a different intrinsic regulatory influence of the CT on cell-associated versus particle associated Env or differential interaction with host or viral proteins. Our findings provide novel insight into the key regulatory potential of the gp41 CT in cell-free and cell-to-cell HIV-1 infection, particularly for short-truncation mutants of <=43 amino acids or mutants with point mutations in the LLP-3 helical domain of the CT, which are able to propagate via cell-to-cell infection in the absence of infectious cell-free virus production. These mutants may also serve as tools to further define the contributions of cell-free and cell-to-cell infection in vitro and in vivo. PMID- 26136567 TI - Longitudinal Detection of Prion Shedding in Saliva and Urine by Chronic Wasting Disease-Infected Deer by Real-Time Quaking-Induced Conversion. AB - Chronic wasting disease (CWD) is an emergent, rapidly spreading prion disease of cervids. Shedding of infectious prions in saliva and urine is thought to be an important factor in CWD transmission. To help to elucidate this issue, we applied an in vitro amplification assay to determine the onset, duration, and magnitude of prion shedding in longitudinally collected saliva and urine samples from CWD exposed white-tailed deer. We detected prion shedding as early as 3 months after CWD exposure and sustained shedding throughout the disease course. We estimated that the 50% lethal dose (LD50) for cervidized transgenic mice would be contained in 1 ml of infected deer saliva or 10 ml of urine. Given the average course of infection and daily production of these body fluids, an infected deer would shed thousands of prion infectious doses over the course of CWD infection. The direct and indirect environmental impacts of this magnitude of prion shedding on cervid and noncervid species are surely significant. IMPORTANCE: Chronic wasting disease (CWD) is an emerging and uniformly fatal prion disease affecting free-ranging deer and elk and is now recognized in 22 U.S. states and 2 Canadian provinces. It is unique among prion diseases in that it is transmitted naturally through wild populations. A major hypothesis to explain CWD's florid spread is that prions are shed in excreta and transmitted via direct or indirect environmental contact. Here we use a rapid in vitro assay to show that infectious doses of CWD prions are in fact shed throughout the multiyear disease course in deer. This finding is an important advance in assessing the risks posed by shed CWD prions to animals as well as humans. PMID- 26136568 TI - Blockage of CD59 Function Restores Activities of Neutralizing and Nonneutralizing Antibodies in Triggering Antibody-Dependent Complement-Mediated Lysis of HIV-1 Virions and Provirus-Activated Latently Infected Cells. AB - Both HIV-1 virions and infected cells use their surface regulators of complement activation (RCA) to resist antibody-dependent complement-mediated lysis (ADCML). Blockage of the biological function of RCA members, particularly CD59 (a key RCA member that controls formation of the membrane attack complex at the terminal stage of the complement activation cascades via all three activation pathways), has rendered both HIV-1 virions and infected cells sensitive to ADCML mediated by anti-Env antibodies (Abs) or sera/plasma from patients at different stages of viral infection. In the current study, we used the well-characterized anti-HIV-1 neutralizing Abs (nAbs), including 2G12, 2F5, and 4E10, and non-nAbs, including 2.2C, A32, N5-i5, and N12-i15, to investigate whether the enhancement of ADCML by blockage of CD59 function is mediated by nAbs, non-nAbs, or both. We found that all nAbs and two non-nAbs (N5-i5 and A32) strongly reacted to three HIV-1 laboratory strains (R5, X4, and R5/X4), six primary isolates, and provirus activated ACH-2 cells examined. In contrast, two non-nAbs, 2.2C and N12-i15, reacted weakly and did not react to these targets, respectively. After blockage of CD59 function, the reactive Abs, regardless of their neutralizing activities, significantly enhanced specific ADCML of HIV-1 virions (both laboratory strains and primary isolates) and provirus-activated latently infected cells. The ADMCL efficacy positively correlated with the enzyme-linked immunosorbent assay reactive intensity of those Abs with their targets. Thus, blockage of RCA function represents a novel approach to restore activities of both nAbs and non nAbs in triggering ADCML of HIV-1 virions and provirus-activated latently infected cells. IMPORTANCE: There is a renewed interest in the potential role of non-nAbs in the control of HIV-1 infection. Our data, for the first time, demonstrated that blockage of the biological function of RCA members rendered both HIV-1 virions and infected cells sensitive to ADCML mediated by not only nAbs but also non-nAbs. Our results are significant in developing novel immune based approaches to restore the functions of nAbs and non-nAbs in the circulation of HIV-1-infected individuals to specifically target and clear HIV-1 virions and infected cells. Our data also provide new insights into the mechanisms by which HIV-1 virions and infected cells escape Ab-mediated immunity and could aid in the design and/or development of therapeutic HIV-1 vaccines. In addition, a combination of antiretroviral therapy with RCA blockage, provirus activators, and therapeutic vaccines may represent a novel approach to eliminate HIV-1 reservoirs, i.e., the infected cells harboring replication-competent proviruses and residual viremia. PMID- 26136569 TI - P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions. AB - HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. IMPORTANCE: Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists. PMID- 26136570 TI - Exploring the Balance between DNA Pressure and Capsid Stability in Herpesviruses and Phages. AB - We have recently shown in both herpesviruses and phages that packaged viral DNA creates a pressure of tens of atmospheres pushing against the interior capsid wall. For the first time, using differential scanning microcalorimetry, we directly measured the energy powering the release of pressurized DNA from the capsid. Furthermore, using a new calorimetric assay to accurately determine the temperature inducing DNA release, we found a direct influence of internal DNA pressure on the stability of the viral particle. We show that the balance of forces between the DNA pressure and capsid strength, required for DNA retention between rounds of infection, is conserved between evolutionarily diverse bacterial viruses (phages lambda and P22), as well as a eukaryotic virus, human herpes simplex 1 (HSV-1). Our data also suggest that the portal vertex in these viruses is the weakest point in the overall capsid structure and presents the Achilles heel of the virus's stability. Comparison between these viral systems shows that viruses with higher DNA packing density (resulting in higher capsid pressure) have inherently stronger capsid structures, preventing spontaneous genome release prior to infection. This force balance is of key importance for viral survival and replication. Investigating the ways to disrupt this balance can lead to development of new mutation-resistant antivirals. IMPORTANCE: A virus can generally be described as a nucleic acid genome contained within a protective protein shell, called the capsid. For many double-stranded DNA viruses, confinement of the large DNA molecule within the small protein capsid results in an energetically stressed DNA state exerting tens of atmospheres of pressures on the inner capsid wall. We show that stability of viral particles (which directly relates to infectivity) is strongly influenced by the state of the packaged genome. Using scanning calorimetry on a bacterial virus (phage lambda) as an experimental model system, we investigated the thermodynamics of genome release associated with destabilizing the viral particle. Furthermore, we compare the influence of tight genome confinement on the relative stability for diverse bacterial and eukaryotic viruses. These comparisons reveal an evolutionarily conserved force balance between the capsid stability and the density of the packaged genome. PMID- 26136571 TI - The Intracellular Domain of the Coxsackievirus and Adenovirus Receptor Differentially Influences Adenovirus Entry. AB - The coxsackievirus and adenovirus receptor (CAR) is a cell adhesion molecule used as a docking molecule by some adenoviruses (AdVs) and group B coxsackieviruses. We previously proposed that the preferential transduction of neurons by canine adenovirus type 2 (CAV-2) is due to CAR-mediated internalization. Our proposed pathway of CAV-2 entry is in contrast to that of human AdV type 5 (HAdV-C5) in nonneuronal cells, where internalization is mediated by auxiliary receptors such as integrins. We therefore asked if in fibroblast-like cells the intracellular domain (ICD) of CAR plays a role in the internalization of the CAV-2 fiber knob (FK(CAV)), CAV-2, or HAdV-C5 when the capsid cannot engage integrins. Here, we show that in fibroblast-like cells, the CAR ICD is needed for FK(CAV) entry and efficient CAV-2 transduction but dispensable for HAdV-C5 and an HAdV-C5 capsid lacking the RGD sequence (an integrin-interacting motif) in the penton. Moreover, the deletion of the CAR ICD further impacts CAV-2 intracellular trafficking, highlighting the crucial role of CAR in CAV-2 intracellular dynamics. These data demonstrate that the CAR ICD contains sequences important for the recruitment of the endocytic machinery that differentially influences AdV cell entry. IMPORTANCE: Understanding how viruses interact with the host cell surface and reach the intracellular space is of crucial importance for applied and fundamental virology. Here, we compare the role of a cell adhesion molecule (CAR) in the internalization of adenoviruses that naturally infect humans and Canidae. We show that the intracellular domain of CAR differentially regulates AdV entry and trafficking. Our study highlights the mechanistic differences that a receptor can have for two viruses from the same family. PMID- 26136572 TI - Role of Nectin-1 and Herpesvirus Entry Mediator as Cellular Receptors for Herpes Simplex Virus 1 on Primary Murine Dermal Fibroblasts. AB - The cellular proteins nectin-1 and herpesvirus entry mediator (HVEM) can both mediate the entry of herpes simplex virus 1 (HSV-1). We have recently shown how these receptors contribute to infection of skin by investigating HSV-1 entry into murine epidermis. Ex vivo infection studies reveal nectin-1 as the primary receptor in epidermis, whereas HVEM has a more limited role. Although the epidermis represents the outermost layer of skin, the contribution of nectin-1 and HVEM in the underlying dermis is still open. Here, we analyzed the role of each receptor during HSV-1 entry in murine dermal fibroblasts that were deficient in expression of either nectin-1 or HVEM or both receptors. Because infection was not prevented by the absence of either nectin-1 or HVEM, we conclude that they can act as alternative receptors. Although HVEM was found to be highly expressed on fibroblasts, entry was delayed in nectin-1-deficient cells, suggesting that nectin-1 acts as the more efficient receptor. In the absence of both receptors, entry was strongly delayed leading to a much reduced viral spread and virus production. These results suggest an unidentified cellular component that acts as alternate but inefficient receptor for HSV-1 on dermal fibroblasts. Characterization of the cellular entry mechanism suggests that HSV-1 can enter dermal fibroblasts both by direct fusion with the plasma membrane and via endocytic vesicles and that this is not dependent on the presence or absence of nectin-1. Entry was also shown to require dynamin and cholesterol, suggesting comparable entry pathways in keratinocytes and dermal fibroblasts. IMPORTANCE: Herpes simplex virus (HSV) is a human pathogen which infects its host via mucosal surfaces or abraded skin. To understand how HSV-1 overcomes the protective barrier of mucosa or skin and reaches its receptors in tissue, it is essential to know which receptors contribute to the entry into individual skin cells. Previously, we have explored the contribution of nectin-1 and herpesvirus entry mediator (HVEM) as receptors for HSV-1 entry into murine epidermis, where keratinocytes form the major cell type. Since the underlying dermis consists primarily of fibroblasts, we have now extended our study of HSV-1 entry to dermal fibroblasts isolated from nectin-1- or HVEM-deficient mice or from mice deficient in both receptors. Our results demonstrate a role for both nectin-1 and HVEM as receptors and suggest a further receptor which appears much less efficient. PMID- 26136573 TI - Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus. AB - Lipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus like particles. IMPORTANCE: The lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry. PMID- 26136574 TI - Impact of Nucleoporin-Mediated Chromatin Localization and Nuclear Architecture on HIV Integration Site Selection. AB - It has been known for a number of years that integration sites of human immunodeficiency virus type 1 (HIV-1) DNA show a preference for actively expressed chromosomal locations. A number of viral and cellular proteins are implicated in this process, but the underlying mechanism is not clear. Two recent breakthrough publications advance our understanding of HIV integration site selection by focusing on the localization of the preferred target genes of integration. These studies reveal that knockdown of certain nucleoporins and components of nucleocytoplasmic trafficking alter integration site preference, not by altering the trafficking of the viral genome but by altering the chromatin subtype localization relative to the structure of the nucleus. Here, we describe the link between the nuclear basket nucleoporins (Tpr and Nup153) and chromatin organization and how altering the host environment by manipulating nuclear structure may have important implications for the preferential integration of HIV into actively transcribed genes, facilitating efficient viral replication. PMID- 26136575 TI - Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa. AB - The polyomavirus tumor (T) antigens play crucial roles in viral replication, transcription, and cellular transformation. They are encoded by partially overlapping open reading frames (ORFs) located in the early region through alternative mRNA splicing. The T expression pattern of the trichodysplasia spinulosa-associated polyomavirus (TSPyV) has not been established yet, hampering further study of its pathogenic mechanisms and taxonomic relationship. Here, we characterized TSPyV T antigen expression in human cell lines transfected with the TSPyV early region. Sequencing of T antigen-encoded reverse transcription-PCR (RT PCR) products revealed three splice donor and acceptor sites creating six mRNA splice products that potentially encode the antigens small T (ST), middle T (MT), large T (LT), tiny T, 21kT, and alternative T (ALTO). Except for 21kT, these splice products were also detected in skin of TSPyV-infected patients. At least three splice products were confirmed by Northern blotting, likely encoding LT, MT, ST, 21kT, and ALTO. Protein expression was demonstrated for LT, ALTO, and possibly MT, with LT detected in the nucleus and ALTO in the cytoplasm of transfected cells. Splice site and start codon mutations indicated that ALTO is encoded by the same splice product that encodes LT and uses internal start codons for initiation. The genuineness of ALTO was indicated by the identification of acetylated N-terminal ALTO peptides by mass spectrometry. Summarizing, TSPyV exhibits an expression pattern characterized by both MT and ALTO expression, combining features of rodent and human polyomaviruses. This unique expression pattern provides important leads for further study of polyomavirus-related disease and for an understanding of polyomavirus evolution. IMPORTANCE: The human trichodysplasia spinulosa-associated polyomavirus (TSPyV) is distinguished among polyomaviruses for combining productive infection with cell-transforming properties. In the research presented here, we further substantiate this unique position by indicating expression of both middle T antigen (MT) and alternative T antigen (ALTO) in TSPyV. So far, none of the human polyomaviruses was shown to express MT, which is considered the most important viral oncoprotein of rodent polyomaviruses. Coexpression of ALTO and MT, which involves a conserved, recently recognized overlapping ORF subject to positive selection, has not been observed before for any polyomavirus. As a result of our findings, this study provides valuable new insights into polyomavirus T gene use and expression. Obviously, these insights will be instrumental in further study and gaining an understanding of TSPyV pathogenicity. More importantly, however, they provide important leads with regard to the interrelationship, functionality, and evolution of polyomaviruses as a whole, indicating that TSPyV is a suitable model virus to study these entities further. PMID- 26136576 TI - Evolution of Influenza B Virus in Kuala Lumpur, Malaysia, between 1995 and 2008. AB - Influenza B virus causes significant disease but remains understudied in tropical regions. We sequenced 72 influenza B viruses collected in Kuala Lumpur, Malaysia, from 1995 to 2008. The predominant circulating lineage (Victoria or Yamagata) changed every 1 to 3 years, and these shifts were associated with increased incidence of influenza B. We also found poor lineage matches with recommended influenza virus vaccine strains. While most influenza B virus lineages in Malaysia were short-lived, one circulated for 3 to 4 years. PMID- 26136577 TI - A Coronavirus E Protein Is Present in Two Distinct Pools with Different Effects on Assembly and the Secretory Pathway. AB - Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi complex membranes, and has cation channel activity in vitro. However, the precise functions of the CoV E protein during infection are still enigmatic. Structural data for the severe acute respiratory syndrome (SARS) CoV E protein suggest that it assembles into a homopentamer. Specific residues in the HD regulate the ion-conducting pore formed by SARS-CoV E in artificial bilayers and the pathogenicity of the virus during infection. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system which require residues in the HD. Here, we use the known structural data from SARS-CoV E to infer the residues important for ion channel activity and the oligomerization of IBV E. We present biochemical data for the formation of two distinct oligomeric pools of IBV E in transfected and infected cells and the residues required for their formation. A high-order oligomer of IBV E is required for the production of virus-like particles (VLPs), implicating this form of the protein in virion assembly. Additionally, disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. IMPORTANCE: CoVs are important human pathogens with significant zoonotic potential, as demonstrated by the emergence of SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. Progress has been made toward identifying potential vaccine candidates in mouse models of CoV infection, including the use of attenuated viruses that lack the CoV E protein or express E-protein mutants. However, no approved vaccines or antiviral therapeutics exist. We previously reported that the hydrophobic domain of the IBV E protein, a putative viroporin, causes disruption of the mammalian secretory pathway when exogenously expressed in cells. Understanding the mechanism of this disruption could lead to the identification of novel antiviral therapeutics. Here, we present biochemical evidence for two distinct oligomeric forms of IBV E, one essential for assembly and the other with a role in disruption of the secretory pathway. Discovery of two forms of CoV E protein will provide additional targets for antiviral therapeutics. PMID- 26136578 TI - Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae. AB - Poxviruses are large DNA viruses of vertebrates and insects causing disease in many animal species, including reptiles, birds, and mammals. Although poxvirus like particles were detected in diseased farmed koi carp, ayu, and Atlantic salmon, their genetic relationships to poxviruses were not established. Here, we provide the first genome sequence of a fish poxvirus, which was isolated from farmed Atlantic salmon. In the present study, we used quantitative PCR and immunohistochemistry to determine aspects of salmon gill poxvirus disease, which are described here. The gill was the main target organ where immature and mature poxvirus particles were detected. The particles were detected in detaching, apoptotic respiratory epithelial cells preceding clinical disease in the form of lethargy, respiratory distress, and mortality. In moribund salmon, blocking of gas exchange would likely be caused by the adherence of respiratory lamellae and epithelial proliferation obstructing respiratory surfaces. The virus was not found in healthy salmon or in control fish with gill disease without apoptotic cells, although transmission remains to be demonstrated. PCR of archival tissue confirmed virus infection in 14 cases with gill apoptosis in Norway starting from 1995. Phylogenomic analyses showed that the fish poxvirus is the deepest available branch of chordopoxviruses. The virus genome encompasses most key chordopoxvirus genes that are required for genome replication and expression, although the gene order is substantially different from that in other chordopoxviruses. Nevertheless, many highly conserved chordopoxvirus genes involved in viral membrane biogenesis or virus-host interactions are missing. Instead, the salmon poxvirus carries numerous genes encoding unknown proteins, many of which have low sequence complexity and contain simple repeats suggestive of intrinsic disorder or distinct protein structures. IMPORTANCE: Aquaculture is an increasingly important global source of high-quality food. To sustain the growth in aquaculture, disease control in fish farming is essential. Moreover, the spread of disease from farmed fish to wildlife is a concern. Serious poxviral diseases are emerging in aquaculture, but very little is known about the viruses and the diseases that they cause. There is a possibility that viruses with enhanced virulence may spread to new species, as has occurred with the myxoma poxvirus in rabbits. Provision of the first fish poxvirus genome sequence and specific diagnostics for the salmon gill poxvirus in Atlantic salmon may help curb this disease and provide comparative knowledge. Furthermore, because salmon gill poxvirus represents the deepest branch of chordopoxvirus so far discovered, the genome analysis provided substantial insight into the evolution of different functional modules in this important group of viruses. PMID- 26136579 TI - Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis. AB - Myd88 signaling is critical to the control of numerous central nervous system (CNS) infections by promoting both innate and adaptive immune responses. Nevertheless, the extent to which Myd88 regulates type I interferon (IFN) versus proinflammatory factors and T cell function, as well as the anatomical site of action, varies extensively with the pathogen. CNS infection by neurotropic coronavirus with replication confined to the brain and spinal cord induces protective IFN-alpha/beta via Myd88-independent activation of melanoma differentiation-associated gene 5 (MDA5). However, a contribution of Myd88 dependent signals to CNS pathogenesis has not been assessed. Infected Myd88(-/-) mice failed to control virus, exhibited enhanced clinical disease coincident with increased demyelination, and succumbed to infection within 3 weeks. The induction of IFN-alpha/beta, as well as of proinflammatory cytokines and chemokines, was impaired early during infection. However, defects in both IFN-alpha/beta and select proinflammatory factors were rapidly overcome prior to T cell recruitment. Myd88 deficiency also specifically blunted myeloid and CD4 T cell recruitment into the CNS without affecting CD8 T cells. Moreover, CD4 T cells but not CD8 T cells were impaired in IFN-gamma production. Ineffective virus control indeed correlated most prominently with reduced antiviral IFN-gamma in the CNS of Myd88( /-) mice. The results demonstrate a crucial role for Myd88 both in early induction of innate immune responses during coronavirus-induced encephalomyelitis and in specifically promoting protective CD4 T cell activation. In the absence of these responses, functional CD8 T cells are insufficient to control viral spread within the CNS, resulting in severe demyelination. IMPORTANCE: During central nervous system (CNS) infections, signaling through the adaptor protein Myd88 promotes both innate and adaptive immune responses. The extent to which Myd88 regulates antiviral type I IFN, proinflammatory factors, adaptive immunity, and pathology is pathogen dependent. These results reveal that Myd88 protects from lethal neurotropic coronavirus-induced encephalomyelitis by accelerating but not enhancing the induction of IFN-alpha/beta, as well as by promoting peripheral activation and CNS accumulation of virus-specific CD4 T cells secreting IFN gamma. By controlling both early innate immune responses and CD4 T cell-mediated antiviral IFN-gamma, Myd88 signaling limits the initial viral dissemination and is vital for T cell-mediated control of viral loads. Uncontrolled viral replication in the absence of Myd88 leads to severe demyelination and pathology despite overall reduced inflammatory responses. These data support a vital role of Myd88 signaling in protective antimicrobial functions in the CNS by promoting proinflammatory mediators and T cell-mediated IFN-gamma production. PMID- 26136580 TI - US primary care physicians' opinions about conscientious refusal: a national vignette experiment. AB - OBJECTIVE: Previous research has found that physicians are divided on whether they are obligated to provide a treatment to which they object and whether they should refer patients in such cases. The present study compares several possible scenarios in which a physician objects to a treatment that a patient requests, in order to better characterise physicians' beliefs about what responses are appropriate. DESIGN: We surveyed a nationally representative sample of 1504 US primary care physicians using an experimentally manipulated vignette in which a patient requests a clinical intervention to which the patient's physician objects. We used multivariate logistic regression models to determine how vignette and respondent characteristics affected respondent's judgements. RESULTS: Among eligible respondents, the response rate was 63% (896/1427). When faced with an objection to providing treatment, referring the patient was the action judged most appropriate (57% indicated it was appropriate), while few physicians thought it appropriate to provide treatment despite one's objection (15%). The most religious physicians were more likely than the least religious physicians to support refusing to accommodate the patient's request (38% vs 22%, OR=1.75; 95% CI 1.06 to 2.86). CONCLUSIONS: This study indicates that US physicians believe it is inappropriate to provide an intervention that violates one's personal or professional standards. Referring seems to be physicians' preferred way of responding to requests for interventions to which physicians object. PMID- 26136584 TI - A Water and Education Provision Intervention Modifies the Diet in Overweight Mexican Women in a Randomized Controlled Trial. AB - BACKGROUND: There is minimal information on the impact of replacing sugar sweetened beverage (SSB) consumption with water on diet quality from randomized controlled trials. OBJECTIVE: We evaluated the effect of a water intake intervention on diet quality in overweight Mexican women. METHODS: Women with a body mass index >=25 and <39, 18-45 y old, and a self-reported high intake of SSBs (>=250 kcal/d) were randomly allocated to either the water and education provision (WEP) group (n = 120) or the education provision (EP) only group (n = 120). Each group received monthly nutrition counseling, and the WEP group received biweekly water deliveries for 9 mo. Three 24-h recalls, anthropometry, and demographic information were collected at baseline, and 3, 6, and 9 mo. Energy, macronutrient, sugar, SSB, fruit and vegetable, salty snack, cake and cookie, and fast food intakes were assessed in study completers (n = 189) classified by intervention assignment and by actual water intake at every time point (low <1200 vs. high >=1200 mL/d). RESULTS: The WEP group reported greater decreases in SSB intake than the EP group (from 20.9% to 10.3% of energy/d vs. from 20.1% to 17.8%). Thirty-eight percent of the EP group and 84.3% of the WEP group reported attaining a water intake >=1200 mL/d. Reductions in energy intake and food groups were similar across intervention groups. However, the high actual water intake group reported greater increases vs. the lower intake group in intake of fruits and vegetables (117 vs. 47 g/d), as well as larger reductions in salty snacks (4.6 vs. 0.7 g/d) and cakes and cookies (31.7 vs. 14.7 g/d). CONCLUSIONS: Other than SSBs, improvements in food group intake did not differ by intervention group in overweight Mexican women. However, post hoc analyses suggested that achieving a high actual water intake was associated with additional beneficial changes in food group intake. This trial was registered at clinicaltrials.gov as NCT01245010. PMID- 26136585 TI - Olive Oil Polyphenols Decrease LDL Concentrations and LDL Atherogenicity in Men in a Randomized Controlled Trial. AB - BACKGROUND: Olive oil polyphenols have shown protective effects on cardiovascular risk factors. Their consumption decreased oxidative stress biomarkers and improved some features of the lipid profile. However, their effects on LDL concentrations in plasma and LDL atherogenicity have not yet been elucidated. OBJECTIVE: Our objective was to assess whether the consumption of olive oil polyphenols could decrease LDL concentrations [measured as apolipoprotein B-100 (apo B-100) concentrations and the total number of LDL particles] and atherogenicity (the number of small LDL particles and LDL oxidizability) in humans. METHODS: The study was a randomized, cross-over controlled trial in 25 healthy European men, aged 20-59 y, in the context of the EUROLIVE (Effect of Olive Oil Consumption on Oxidative Damage in European Populations) study. Volunteers ingested 25 mL/d raw low-polyphenol-content olive oil (LPCOO; 366 mg/kg) or high-polyphenol-content olive oil (HPCOO; 2.7 mg/kg) for 3 wk. Interventions were preceded by 2-wk washout periods. Effects of olive oil polyphenols on plasma LDL concentrations and atherogenicity were determined in the sample of 25 men. Effects on lipoprotein lipase (LPL) gene expression were assessed in another sample of 18 men from the EUROLIVE study. RESULTS: Plasma apo B-100 concentrations and the number of total and small LDL particles decreased (mean +/- SD: by 5.94% +/- 16.6%, 11.9% +/- 12.0%, and 15.3% +/- 35.1%, respectively) from baseline after the HPCOO intervention. These changes differed significantly from those after the LPCOO intervention, which resulted in significant increases of 6.39% +/- 16.6%, 4.73% +/- 22.0%, and 13.6% +/- 36.4% from baseline (P < 0.03). LDL oxidation lag time increased by 5.0% +/- 10.3% from baseline after the HPCOO intervention, which was significantly different only relative to preintervention values (P = 0.038). LPL gene expression tended to increase by 26% from baseline after the HPCOO intervention (P = 0.08) and did not change after the LPCOO intervention. CONCLUSION: The consumption of olive oil polyphenols decreased plasma LDL concentrations and LDL atherogenicity in healthy young men. This trial was registered at www.controlled-trials.com as ISRCTN09220811. PMID- 26136586 TI - Milk Polar Lipids Affect In Vitro Digestive Lipolysis and Postprandial Lipid Metabolism in Mice. AB - BACKGROUND: Polar lipid (PL) emulsifiers such as milk PLs (MPLs) may affect digestion and subsequent lipid metabolism, but focused studies on postprandial lipemia are lacking. OBJECTIVE: We evaluated the impact of MPLs on postprandial lipemia in mice and on lipid digestion in vitro. METHODS: Female Swiss mice were gavaged with 150 MUL of an oil-in-water emulsion stabilized with 5.7 mg of either MPLs or soybean PLs (SPLs) and killed after 1, 2, or 4 h. Plasma lipids were quantified and in the small intestine, gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction. Emulsions were lipolyzed in vitro using a static human digestion model; triglyceride (TG) disappearance was followed by thin-layer chromatography. RESULTS: In mice, after 1 h, plasma TGs tended to be higher in the MPL group than in the SPL group (141 MUg/mL vs. 90 MUg/mL; P = 0.07) and nonesterified fatty acids (NEFAs) were significantly higher (64 MUg/mL vs. 44 MUg/mL; P < 0.05). The opposite was observed after 4 h with lower TGs (21 MUg/mL vs. 35 MUg/mL; P < 0.01) and NEFAs (20 MUg/mL vs. 32 MUg/mL; P < 0.01) in the MPL group compared with the SPL group. This was associated at 4 h with a lower gene expression of apolipoprotein B (Apob) and Secretion Associated, Ras related GTPase 1 gene homolog B (Sar1b), in the duodenum of MPL mice compared with SPL mice (P < 0.05). In vitro, during the intestinal phase, TGs were hydrolyzed more in the MPL emulsion than in the SPL emulsion (decremental AUCs were 1750%/min vs. 180%/min; P < 0.01). MPLs enhance lipid intestinal hydrolysis and promote more rapid intestinal lipid absorption and sharper kinetics of lipemia. CONCLUSIONS: Postprandial lipemia in mice can be modulated by emulsifying with MPLs compared with SPLs, partly through differences in chylomicron assembly, and TG hydrolysis rate as observed in vitro. MPLs may thereby contribute to the long-term regulation of lipid metabolism. PMID- 26136581 TI - The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes. AB - All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions. PMID- 26136587 TI - PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity. AB - BACKGROUND: Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. OBJECTIVE: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. METHODS: PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m(2)) >=25; mean +/- SD age: 59.7 +/- 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI >=30; mean +/- SD age: 57.1 +/- 4.9 y) from the alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and alpha-tocopherol were measured by HPLC in both cohorts. beta-Carotene concentrations in the ATBC study were measured by using HPLC. RESULTS: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (beta = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI >=30 (ATBC study; beta = -0.043, P = 0.04). CONCLUSION: We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations. PMID- 26136588 TI - Antenatal Iron-Folic Acid Supplementation Reduces Neonatal and Under-5 Mortality in Nepal. AB - BACKGROUND: Antenatal iron-folic acid (IFA) supplementation improves maternal anemia and poor pregnancy outcomes. Antenatal use of IFA supplements also has an effect on child survival. OBJECTIVE: The current study investigated the effect of antenatal IFA supplements on the risk of childhood mortality in Nepal over a 15-y period from 1996 to 2011. METHODS: Survival information of 12,891 singleton most recent live-born infants from pooled 2001, 2006, and 2011 Nepal Demographic and Health Surveys was used. Primary outcomes were mortality indicators in children <5 y of age and the main exposure variable was use of IFA supplements. Data were analyzed by using STATA 13.1 (StataCorp) and were adjusted for the cluster sampling design. Analyses used multivariate Cox proportional hazards regression adjusted for potential confounders. RESULTS: Antenatal use of IFA supplements significantly reduced the risk of early neonatal deaths by 45% [adjusted HR (aHR): 0.55; 95% CI: 0.38, 0.79] and total neonatal deaths by 42% (aHR: 0.58; 95% CI: 0.39, 0.85). Similarly, the risk of infant and under-5 mortality was significantly reduced by 32% and 48%, respectively. For mothers who started IFA at 1-4 mo of pregnancy and used 150-240 supplements, neonatal and under-5 mortality were significantly reduced by 55% (aHR: 0.45; 95% CI: 0.24, 0.85) and 57% (aHR: 0.43; 95% CI: 0.23, 0.78), respectively. Population attributable risk estimates found 15% of under-5 deaths were attributed to nonuse of IFA, and 29,000 under-5 deaths could be prevented in the next 5 y with universal IFA coverage. CONCLUSIONS: Antenatal IFA supplementation significantly reduces the risk of neonatal and under-5 deaths in Nepal. The greatest effect on child survival was found in women who started IFA early in pregnancy and took 150-240 supplements. Universal IFA coverage could improve neonatal and child survival. PMID- 26136589 TI - Food Price Spikes Are Associated with Increased Malnutrition among Children in Andhra Pradesh, India. AB - BACKGROUND: Global food prices have risen sharply since 2007. The impact of food price spikes on the risk of malnutrition in children is not well understood. OBJECTIVE: We investigated the associations between food price spikes and childhood malnutrition in Andhra Pradesh, one of India's largest states, with >85 million people. Because wasting (thinness) indicates in most cases a recent and severe process of weight loss that is often associated with acute food shortage, we tested the hypothesis that the escalating prices of rice, legumes, eggs, and other staples of Indian diets significantly increased the risk of wasting (weight for-height z scores) in children. METHODS: We studied periods before (2006) and directly after (2009) India's food price spikes with the use of the Young Lives longitudinal cohort of 1918 children in Andhra Pradesh linked to food price data from the National Sample Survey Office. Two-stage least squares instrumental variable models assessed the relation of food price changes to food consumption and wasting prevalence (weight-for-height z scores). RESULTS: Before the 2007 food price spike, wasting prevalence fell from 19.4% in 2002 to 18.8% in 2006. Coinciding with India's escalating food prices, wasting increased significantly to 28.0% in 2009. These increases were concentrated among low- (chi(2): 21.6, P < 0.001) and middle- (chi(2): 25.9, P < 0.001) income groups, but not among high income groups (chi(2): 3.08, P = 0.079). Each 10.0 rupee ($0.170) increase in the price of rice/kg was associated with a drop in child-level rice consumption of 73.0 g/d (beta: -7.30; 95% CI: -10.5, -3.90). Correspondingly, lower rice consumption was significantly associated with lower weight-for-height z scores (i.e., wasting) by 0.005 (95% CI: 0.001, 0.008), as seen with most other food categories. CONCLUSION: Rising food prices were associated with an increased risk of malnutrition among children in India. Policies to help ensure the affordability of food in the context of economic growth are likely critical for promoting children's nutrition. PMID- 26136590 TI - Milk Consumption after Age 9 Years Does Not Predict Age at Menarche. AB - BACKGROUND: Regular milk consumption during childhood and adolescence is recommended for bone health. However, milk consumption increases circulating insulin-like growth factor I concentrations, and may also accelerate puberty. OBJECTIVE: We prospectively investigated the association between milk consumption and age at menarche in the Growing Up Today Study. METHODS: Study participants were 5583 US girls who were premenarcheal and ages 9-14 y in 1996. Girls were followed through 2001, at which time 97% of noncensored participants had reported menarche. Frequency of milk and meat consumption was calculated with the use of annual youth/adolescent food frequency questionnaires from 1996-1998. Intake of related nutrients was also measured. Age at menarche was self-reported annually through 2001. RESULTS: During follow-up, 5227 girls attained menarche over 10,555 accrued person-years. In models adjusted for dietary and sociodemographic predictors of menarche, frequency of milk consumption did not predict age at onset of menarche (for >3 glasses of milk/d vs. 1.1-4 glasses/wk, HR: 0.93; 95% CI: 0.83, 1.04). After additional adjustment for body size, premenarcheal girls consuming >3 glasses of milk daily were 13% less likely (95% CI: -3%, -23%; P trend: <0.01) to attain menarche in the next month relative to those consuming 1.1-4 glasses/wk. Neither total meat nor red meat consumption was associated with age at menarche. CONCLUSIONS: Our findings suggest that regular consumption of milk in girls aged >=9 y is unlikely to substantially affect age at onset of menarche. Studies assessing associations between diet in early childhood and pubertal timing may be more illuminating. PMID- 26136591 TI - Comparable Dietary Patterns Describe Dietary Behavior across Ethnic Groups in the Netherlands, but Different Elements in the Diet Are Associated with Glycated Hemoglobin and Fasting Glucose Concentrations. AB - BACKGROUND: Ethnic minority populations in Western societies suffer from a disproportionate burden of type 2 diabetes (T2D). Insight into the role of dietary patterns in T2D may assist public health nutrition efforts in addressing these health disparities. OBJECTIVE: We explored the association between dietary patterns and biomarkers of T2D in 5 ethnic groups living in Amsterdam, Netherlands. METHODS: A total of 3776 men and women aged 18-70 y of Dutch, South Asian Surinamese, African-Surinamese, Turkish, and Moroccan origin from the HELIUS (HEalthy LIfe in an Urban Setting) study were included. Diet was assessed by using a food-frequency questionnaire, and dietary patterns were derived separately per ethnic group. First, food group-based dietary patterns were derived by using principal components analysis and the association with glycated hemoglobin (HbA1c) and plasma fasting glucose was assessed by using multivariable linear regression. Second, biomarker-driven dietary patterns based on HbA1c and fasting glucose concentrations were derived by applying reduced rank regression. RESULTS: Two comparable food group-based dietary patterns were identified in each ethnic group: a "meat and snack" pattern and a "vegetable" pattern. The meat-and snack pattern derived within the Dutch origin population was significantly associated with HbA1c (beta = 0.09; 95% CI: 0.00, 0.19) and fasting glucose (beta = 0.18; 95% CI: 0.09, 0.26) concentrations. A biomarker-derived pattern characterized by red and processed meat was observed among Dutch-origin participants; however, among ethnic minority groups, this pattern was characterized by other foods including ethnicity-specific foods (e.g., roti, couscous). CONCLUSIONS: Although similar food group dietary patterns were derived within 5 ethnic groups, the association of the meat-and-snack pattern with fasting glucose concentrations differed by ethnicity. Taken together with the finding of ethnic differences in biomarker-driven dietary patterns, our results imply that addressing T2D risk in multiethnic populations requires ethnicity specific approaches. PMID- 26136592 TI - Breastfeeding Practices among Poor Women in Mesoamerica. AB - BACKGROUND: Breastfeeding is an effective intervention to reduce pediatric morbidity and mortality. The prevalence of practices and predictors of breastfeeding among the poor in Mesoamerica has not been well described. OBJECTIVES: We estimated the prevalence of ever breastfeeding, early initiation of breastfeeding, exclusive breastfeeding, and breastfeeding between 6 mo and 2 y of age using household survey data for the poorest quintile of families living in 6 Mesoamerican countries. We also assessed the predictors of breastfeeding behaviors to identify factors amenable to policy interventions. METHODS: We analyzed data from 12,529 children in Guatemala, Honduras, Mexico (Chiapas State), Nicaragua, Panama, and El Salvador using baseline survey data from the Salud Mesoamerica 2015 Initiative. We created multivariable Poisson regression models with robust variance estimates to calculate adjusted risk ratios (aRRs) and 95% CIs for breastfeeding outcomes and to control for sociodemographic and healthcare-related factors. RESULTS: Approximately 97% of women in all countries breastfed their child at least once, and 65.1% (Nicaragua) to 79.0% (Panama) continued to do so between 6 mo and 2 y of age. Breastfeeding in the first hour of life varied by country (P < 0.001), with the highest proportion reported in Panama (89.8%) and the lowest in El Salvador (65.6%). Exclusive breastfeeding also varied by country (P = 0.037), ranging from 44.5% in Panama to 76.8% in Guatemala. For every 20% increase in the proportion of peers who exclusively breastfed, there was an 11% (aRR: 1.11, 95% CI: 1.04, 1.18) increase in the likelihood of exclusive breastfeeding. CONCLUSION: Our study revealed significant variation in the prevalence of breastfeeding practices by poor women across countries surveyed by the Salud Mesoamerica 2015 initiative. Future interventions to promote exclusive breastfeeding should consider ways to leverage the role of the community in supporting individual women. PMID- 26136593 TI - Normal or High Polyphenol Concentration in Orange Juice Affects Antioxidant Activity, Blood Pressure, and Body Weight in Obese or Overweight Adults. AB - BACKGROUND: The consumption of orange juice may lead to reduced oxidative stress and may enhance the antioxidant defense system. OBJECTIVE: The aim was to evaluate the effects of the intake of orange juice containing either normal (NPJ) or high (HPJ) concentrations of polyphenols (299 and 745 mg/d, respectively) on the antioxidant defense system, oxidative stress biomarkers, and clinical signs of metabolic syndrome in 100 nonsmoking subjects who were either overweight or obese. METHODS: A randomized, double-blind crossover study was conducted over two 12-wk periods with a 7-wk washout period. The effects on enzymatic and nonenzymatic blood antioxidant defense systems, urinary and plasma oxidative stress biomarkers, and clinical signs of metabolic syndrome were evaluated before and after an intervention with both of the orange juices. Paired t tests and linear mixed-effects models were used to evaluate the effects of juice, time, and interactions. RESULTS: The intake of either NPJ or HPJ led to a decrease in urinary 8-hydroxy-2'-deoxyguanosine (NPJ: 935 +/- 134 to 298 +/- 19 ng/mg creatinine; HPJ: 749 +/- 84 to 285 +/- 17 ng/mg creatinine), 8-iso-prostaglandin F2alpha (NPJ: 437 +/- 68 to 156 +/- 14 ng/mg creatinine; HPJ: 347 +/- 43 to 154 +/- 13 ng/mg creatinine), erythrocyte catalase, and glutathione reductase activities. A decrease was also observed in body mass index, waist circumference, and leptin (all P < 0.05). The NPJ intervention decreased systolic and diastolic blood pressures (systolic blood pressure: 128 +/- 1 to 124 +/- 2 mm Hg; diastolic blood pressure: 79 +/- 1 to 76 +/- 1 mm Hg), whereas the HPJ intervention increased erythrocyte superoxide dismutase (SOD) activity (17.7 +/- 1.5 to 23.1 +/- 1.7 U/mg hemoglobin). CONCLUSIONS: Our results show that the consumption of either NPJ or HPJ protected against DNA damage and lipid peroxidation, modified several antioxidant enzymes, and reduced body weight in overweight or obese nonsmoking adults. Only blood pressure and SOD activity were influenced differently by the different flavanone supplementations. This trial was registered at clinicaltrials.gov as NCT01290250. PMID- 26136594 TI - Higher Serum 25-Hydroxyvitamin D and Lower Plasma Glucose Are Associated with Larger Gray Matter Volume but Not with White Matter or Total Brain Volume in Dutch Community-Dwelling Older Adults. AB - BACKGROUND: Previous studies have shown beneficial associations between 25 hydroxyvitamin D [25(OH)D] status and cognitive performance, but results are inconclusive. Studies on 25(OH)D status and brain volumetric measures may provide more insight in the potential role of vitamin D in cognitive performance. OBJECTIVES: The aims of this study were to cross-sectionally investigate the association between vitamin D status and brain tissue volumes in 217 Dutch community-dwelling older adults aged >=65 y and to examine whether surrogate markers of glucose homeostasis act as modifiers in these associations. METHODS: Serum 25(OH)D, plasma glucose, and plasma insulin were analyzed, serving as exposure measures. Estimates of total brain volume, gray matter volume, and white matter volume were obtained using MRI, serving as outcome measures. Associations of serum 25(OH)D, plasma glucose, and plasma insulin concentrations with brain tissue volumes were evaluated using multiple linear regression analyses. Potential effect modification by glucose homeostasis in the association between 25(OH)D and brain volumetric measures was examined by stratification and testing for interaction. RESULTS: After full adjustment, higher serum 25(OH)D concentrations and lower plasma glucose concentrations were associated with larger gray matter volume, [beta +/- SE: 0.20 +/- 0.08 mL (P = 0.02) and -3.26 +/ 1.59 mL (P = 0.04), respectively]. There were no associations between serum 25(OH)D and plasma insulin concentrations with total brain volume and white matter volume. Furthermore, there was no evidence for a mediation or modification effect of plasma glucose on the associations between serum 25(OH)D and brain tissue volumes. CONCLUSION: Higher serum 25(OH)D and lower plasma glucose are associated with larger gray matter volume, but not white matter or total brain volume, in a population of Dutch adults aged >=65 y. This trial was registered at clinicaltrials.gov as NCT00696514. PMID- 26136595 TI - Hypersensitivity pneumonitis in a high school teacher. AB - Hypersensitivity pneumonitis (HP) is an inflammatory lung disease mediated by an immunological response to an inhaled antigen. Outbreaks of HP have been reported in industrial settings where manufacturing workers are exposed to water-based metalworking fluids (MWFs). Water-based MWFs promote growth of microorganisms and can be easily aerosolized and are thus potential aetiological agents of HP. We present a case of HP caused by exposure to water-based MWF in a vocational high school teacher. Culture of MWF used at his school grew Pseudomonas pseudoalcaligenes. This is the first known report of MWF-induced HP outside an industrial setting. The growth of Pseudomonas spp in this case recalls the earliest reports of the microbiology of MWF-induced HP and suggests that routine bacterial culture may be useful in the diagnosis of HP in workplaces without standard cleaning and biocide regulations. PMID- 26136596 TI - Associations of chronic embitterment among NHS staff. AB - BACKGROUND: Chronic embitterment is commonly recognized among people seen by occupational health professionals, but its associations remain unclear. AIMS: To investigate the associations of chronic embitterment with procedural justice, the psychological work contract, depression and the Health & Safety Executive's Management Standards Indicator Tool as well as selected employment variables. METHODS: A sample of consecutive attendees at occupational health in a single NHS Trust were asked to complete a set of validated questionnaires and give further information about sickness absence and their work. RESULTS: The sample (n = 236) was representative of those attending this occupational health department. Staff showing embitterment rated procedural justice and organizational support lower than other staff and were significantly more likely to have taken sickness absence, uncertified as well as certified. Uncertified sickness absence was almost universal in embittered staff. Although depression was significantly more prevalent among embittered staff, the majority of embittered staff were not depressed. Of those who scored as embittered and depressed or anxious, 93% had had certified sickness absence in the previous 12 months. On the Management Standards Indicator Tool, embittered individuals had significantly lower scores than others on Manager and Peer Support, Role, and Change subscales. CONCLUSIONS: Although the data are cross-sectional and self-reported, they provide evidence of the burden on organizations of chronic embitterment among their staff, particularly in terms of sickness absence. Staff who are embittered perceive their organization as unsupportive of them, and as showing low levels of procedural justice. PMID- 26136597 TI - Loss of Arabidopsis 5'-3' Exoribonuclease AtXRN4 Function Enhances Heat Stress Tolerance of Plants Subjected to Severe Heat Stress. AB - mRNA degradation plays an important role in the rapid and dynamic alteration of gene expression in response to environmental stimuli. Arabidopsis 5'-3' exoribonuclease (AtXRN4), a homolog of yeast Xrn1p, functions after a de-capping step in the degradation of uncapped RNAs. While Xrn1p-dependent degradation of mRNA is the main process of mRNA decay in yeast, information pertaining to the targets of XRN4-based degradation in plants is limited. In order to better understand the biological function of AtXRN4, the current study examined the survivability of atxrn4 mutants subjected to heat stress. The results indicated that atxrn4 mutants, compared with wild-type plants, exhibited an increased survival rate when subjected to a short-term severe heat stress. A microarray and mRNA decay assay showed that loss of AtXRN4 function caused a reduction in the degradation of heat shock factor A2 (HSFA2) and ethylene response factor 1 (ERF1) mRNA. The heat stress tolerance phenotype of atxrn4 mutants was significantly reduced or lost by mutation of HSFA2, a known key regulator of heat acclimation, thus indicating that HSFA2 is a target gene of AtXRN4-mediated mRNA degradation both under non-stress conditions and during heat acclimation. These results demonstrate that AtXRN4-mediated mRNA degradation is linked to the suppression of heat acclimation. PMID- 26136600 TI - Chiropractic techniques and technologies. PMID- 26136598 TI - Loss of Arabidopsis thaliana Seed Dormancy is Associated with Increased Accumulation of the GID1 GA Hormone Receptors. AB - Dormancy prevents seeds from germinating under favorable conditions until they have experienced dormancy-breaking conditions, such as after-ripening through a period of dry storage or cold imbibition. Abscisic acid (ABA) hormone signaling establishes and maintains seed dormancy, whereas gibberellin (GA) signaling stimulates germination. ABA levels decrease and GA levels increase with after ripening and cold stratification. However, increasing GA sensitivity may also be critical to dormancy loss since increasing seed GA levels are detectable only with long periods of after-ripening and imbibition. After-ripening and cold stratification act additively to enhance GA hormone sensitivity in ga1-3 seeds that cannot synthesize GA. Since the overexpression of the GA receptor GID1 (GIBBERELLIN-INSENSITIVE DWARF1) enhanced this dormancy loss, and because gid1a gid1b gid1c triple mutants show decreased germination, the effects of dormancy breaking treatments on GID1 mRNA and protein accumulation were examined. Partial after-ripening resulted in increased GID1b, but not GID1a or GID1c mRNA levels. Cold imbibition stimulated the accumulation of all three GID1 transcripts, but resulted in no increase in GA sensitivity during ga1-3 seed germination unless seeds were also partially after-ripened. This is probably because after-ripening was needed to enhance GID1 protein accumulation, independently of transcript abundance. The rise in GID1b transcript with after-ripening was not associated with decreased ABA levels, suggesting there is ABA-independent GID1b regulation by after-ripening and the 26S proteasome. GA and the DELLA RGL2 repressor of GA responses differentially regulated the three GID1 transcripts. Moreover, DELLA RGL2 appeared to switch between positive and negative regulation of GID1 expression in response to dormancy-breaking treatments. PMID- 26136601 TI - Validity of palpation of the C1 transverse process: comparison with a radiographic reference standard. AB - OBJECTIVES: Primary goal: to determine the validity of C1 transverse process (TVP) palpation compared to an imaging reference standard. METHODS: Radiopaque markers were affixed to the skin at the putative location of the C1 TVPs in 21 participants receiving APOM radiographs. The radiographic vertical distances from the marker to the C1 TVP, mastoid process, and C2 TVP were evaluated to determine palpatory accuracy. RESULTS: Interexaminer agreement for radiometric analysis was "excellent." Stringent accuracy (marker placed +/-4mm from the most lateral projection of the C1 TVP) = 57.1%; expansive accuracy (marker placed closer to contiguous structures) = 90.5%. Mean Absolute Deviation (MAD) = 4.34 (3.65, 5.03) mm; root-mean-squared error = 5.40mm. CONCLUSIONS: Manual palpation of the C1 TVP can be very accurate and likely to direct a manual therapist or other health professional to the intended diagnostic or therapeutic target. This work is relevant to manual therapists, anesthetists, surgeons, and other health professionals. PMID- 26136602 TI - Improvement in clinical outcomes after dry needling in a patient with occipital neuralgia. AB - The primary purpose of this case report is to outline the diagnosis, intervention and clinical outcome of a patient presenting with occipital neuralgia. Upon initial presentation, the patient described a four-year history of stabbing neck pain and headaches. After providing informed consent, the patient underwent a total of four dry needling (DN) sessions over a two-week duration. During each of the treatment sessions, needles were inserted into the trapezii and suboccipital muscles. Post-intervention, the patient reported a 32-point change in her neck disability index score along with a 28-point change in her headache disability index score. Thus, it appears that subsequent four sessions of DN over two weeks, our patient experienced meaningful improvement in her neck pain and headaches. To the best of our knowledge, this is the first case report describing DN to successfully improve clinical outcomes in a patient diagnosed with occipital neuralgia. PMID- 26136603 TI - Sexual harassment of female chiropractors by their patients: a pilot survey of faculty at the Canadian Memorial Chiropractic College. AB - BACKGROUND: The purpose of this study was to survey a group of female chiropractors and inquire as to whether or not they had been sexually harassed by their patients. METHODS: An online questionnaire was emailed via Survey Monkey to 47 female faculty members at the Canadian Memorial Chiropractic College (CMCC). Respondents were asked if they had been sexual harassed and, if so, the characteristics of the incident(s), their response to it, how serious they perceived the problem to be and whether or not they felt prepared to deal with it. RESULTS: Nineteen of 47 questionnaires were completed and returned. Of these 19, eight respondents reported being sexually harassed by a patient (all male), most commonly within the first 5 years of practice and most commonly involving a 'new' patient. It was rarely anticipated. The nature of the harassment varied and respondents often ignored the incident. Most respondents perceive this to be a problem facing female chiropractors. DISCUSSION: Although this is the first survey of its kind, this is a significant problem facing other healthcare professionals. CONCLUSIONS: Among this group of respondents, sexual harassment by patients was a common occurrence. More training on how to handle it, during either a student's chiropractic education or offered as a continuing education program, may be warranted. PMID- 26136604 TI - What effect does chiropractic treatment have on gastrointestinal (GI) disorders: a narrative review of the literature. AB - The purpose of this study was to provide a narrative review of the literature of studies describing the management of disorders of the gastro-intestinal (GI) tract using 'chiropractic therapy' broadly defined here as spinal manipulation therapy, mobilizations, soft tissue therapy, modalities and stretches. Search limiters include access to full text studies published between 1980 and November 2012 in peer-reviewed journals, English language only involving human subjects. Twenty-one articles were found that met our inclusion criteria. Retrievable articles varied from case reports to clinical trials to review articles of management options. The majority of articles chronicling patient experiences under chiropractic care reported they demonstrated mild to moderate improvements in presenting symptoms. No adverse side effects were reported. This suggests chiropractic care can be considered as an adjunctive therapy for patients with various GI conditions providing there are no co-morbidities. PMID- 26136605 TI - R + C Factors and Sacro Occipital Technique Orthopedic Blocking: a pilot study using pre and post VAS assessment. AB - INTRODUCTION: The concept of a systematic or predictive relationship between distant vertebral levels distinct from accumulative functional compensatory mechanisms, such as in scoliosis, has been perpetuated within chiropractic technique systems based on clinical observation and experience. This study seeks to investigate this relationship between the cervical and lumbar vertebrae. METHODS: Patients (experimental group n=26 and control group n=12) were selected from the patient base of one office, and were limited to patients that had sensitivity at specific cervical reflex points. Using a pre and post outcome measurement and sacro occipital technique R + C protocols, the related lumbar vertebra was adjusted in the direction indicated by the cervical vertebral sensitivity. RESULTS: Statistical analysis revealed there was a statistically significant difference between pre- and post-VAS measurements and found that the notable difference in mean change in VAS scores were statistically significantly different between the experimental and control groups (p < .001). CONCLUSION: The findings of this study suggest that further research into cervical and lumbar vertebra interrelationships, and the efficacy of orthopedic block treatment, may be warranted. Further studies are needed to confirm whether a causal relationship exists between lumbar manipulation and decreased cervical spine sensitivity. PMID- 26136606 TI - Use of spinal manipulation in a rheumatoid patient presenting with acute thoracic pain: a case report. AB - BACKGROUND: There is limited research related to spinal manipulation of uncomplicated thoracic spine pain and even less when pain is associated with comorbid conditions such as rheumatoid arthritis. In the absence of trial evidence, clinical experience and appropriate selection of the type of intervention is important to informing the appropriate management of these cases. CASE PRESENTATION: We present a case of a patient with long standing rheumatoid arthritis who presented with acute thoracic pain. The patient was diagnosed with costovertebral joint dysfunction and a myofascial strain of the surrounding musculature. The patient was unresponsive to treatment involving a generalized manipulative technique; however, improved following the administration of a specific applied manipulation with modified forces. The patient was deemed recovered and discharged with ergonomic and home care recommendations. DISCUSSION: This case demonstrates a clinical situation where there is a paucity of research to guide management, thus clinicians must rely on experience and patient preferences in the selection of an appropriate and safe therapeutic intervention. The case highlights the need to contextualize the apparent contraindication of manipulation in patients with rheumatoid arthritis and calls for further research. Finally the paper advances evidence based decision making that balances the available research, clinical experience, as well as patient preferences. PMID- 26136607 TI - The examination of soft tissue compliance in the thoracic region for the development of a spinal manipulation training mannequin. AB - PURPOSE: To determine if the soft tissue compliance of the thoracic paraspinal musculature differs based on gender and body type to help create a foam human analogue mannequin to assist in the training of spinal manipulative therapy. METHODS: 54 volunteers were grouped based on their gender and body types. In the prone position, thoracic paraspinal soft tissue compliance was measured at T1, T3 T6, T9 and T12 vertebrae levels bilaterally using a tissue compliance meter. RESULTS: There was no significant difference in tissue compliance when comparing the genders except at T1 (p=0.026). When comparing body types, significantly higher tissue compliance was found between endomorphs and the other groups. No significant difference was found between ectomorphs and mesomorphs. The compliance for the participants in this study ranged from 0.122 mm/N to 0.420 mm/N. CONCLUSION: There are significant differences in thoracic spine soft tissue compliance in healthy asymptomatic patients between genders in the upper thoracic spine, and between different body types throughout the thoracic spine. It may be beneficial to create multiple versions of practice mannequins to simulate variations amongst different patients. PMID- 26136608 TI - Inter-examiner reliability of the interpretation of paraspinal thermographic pattern analysis. AB - INTRODUCTION: A few spinal manipulation techniques use paraspinal surface thermography as an examination tool that informs clinical-decision making; however, inter-examiner reliability of this interpretation has not been reported. The purpose of this study was to report inter-examiner reliability for classifying cervical paraspinal thermographic findings. METHODS: Seventeen doctors of chiropractic self-reporting a minimum of 2 years of experience using thermography classified thermographic scans into categories (full pattern, partial +, partial, partial -, and adaptation). Kappa statistics (k) were calculated to determine inter-examiner reliability. RESULTS: Overall inter examiner reliability was fair (k=0.43). There was good agreement for identifying full pattern (k=0.73) and fair agreement for adaptation (k=0.55). Poor agreement was noted in partial categories (k=0.05-0.22). CONCLUSION: Inter-examiner reliability demonstrated fair to good agreement for identifying comparable (full pattern) and disparate (adaptation) thermographic findings; agreement was poor for those with moderate similarity (partial). Further research is needed to determine whether thermographic findings should be used in clinical decision making for spinal manipulation. PMID- 26136609 TI - Testing an association between baseline resting pulse rate averages and short term changes in resting pulse rates: A pilot study. AB - INTRODUCTION: Resting heart (pulse) rate (RPR) monitoring may be a useful neurological assessment tool in chiropractic practice. Lower RPR generally reflects a better level of fitness and health status than higher RPR. However, the clinical significance of short-term changes in RPR remains unknown. The purpose of this study was to take an initial step towards understanding the clinical significance of short-term RPR changes, first, by describing short-term RPR changes between duplicated measurements, and second, by comparing RPR changes between groups with lower and higher baseline RPR. METHODS: Seventy-three healthy adult volunteers received an RPR measurement on two days within a 1-week period. The mean difference between the two measurements (RPR change) in patients with lower versus higher baseline RPR was compared. RESULTS: Mean RPR change in the low baseline group was -0.3 BPM (95% confidence interval [CI] = -2.7 to 2.1 BPM) whereas in the high baseline group, it was +4.4 BPM (95% CI = 1.2 to 7.6). This difference between groups was statistically significant (P = 0.02) Testing an association between baseline resting pulse rate averages and short-term changes in resting pulse rates: A pilot study with a large effect size (Cohen's d = 0.57). CONCLUSION: In this pilot study, a higher RPR at baseline was associated with increased RPR change, whereas a lower baseline RPR was associated with a stable or reduced RPR change. A future main study with a larger sample size and longer follow-up period is needed to better characterize both the natural variation of RPR over multiple repeated measurements, and the clinical significance of short-term RPR changes in terms of predicting longer-term health outcomes. PMID- 26136610 TI - Craniocervical chiropractic procedures - a precis of upper cervical chiropractic. AB - Presented here is a narrative review of upper cervical procedures intended to facilitate understanding and to increase knowledge of upper cervical chiropractic care. Safety, efficacy, common misconceptions, and research are discussed, allowing practitioners, chiropractic students, and the general public to make informed decisions regarding utilization and referrals for this distinctive type of chiropractic care. Upper cervical techniques share the same theoretical paradigm in that the primary subluxation exists in the upper cervical spine. These procedures use similar assessments to determine if spinal intervention is necessary and successful once delivered. The major difference involves their use of either an articular or orthogonal radiograph analysis model when determining the presence of a misalignment. Adverse events following an upper cervical adjustment consist of mild symptomatic reactions of short-duration (< 24-hours). Due to a lack of quality and indexed references, information contained herein is limited by the significance of literature cited, which included non-indexed and/or non-peer reviewed sources. PMID- 26136611 TI - Marriage Trajectories and Health Risk Behaviors Throughout Adulthood Among Urban African Americans. AB - Although previous studies have identified a protective effect of marriage on risky health behaviors, gaps remain in our understanding of how marriage improves health, particularly among African Americans. This study uses longitudinal data to take selection into account and examines whether marital trajectories that incorporate timing, stability, and duration of marriage affect health risk behaviors among a community cohort of urban African Americans followed for 35 years (N = 1,049). For both men and women, we find six marital trajectories. Men and women in consistently married trajectories are less likely to smoke, drink heavily (women only), and use illegal drugs than those in unmarried or previously married trajectories. Late marrying men do not fare worse in midlife than men in earlier marrying trajectories, but late marrying women show increased risk of midlife drug use. Results suggest policies supporting marriage may have an impact on health but only if stable unions are achieved. PMID- 26136612 TI - Optimization of light sources for prostate photodynamic therapy. AB - To deliver uniform photodynamic dose to the prostate gland, it is necessary to develop algorithms that optimize the location and strength (emitted power * illumination time) of each light source. Since tissue optical properties may change with time, rapid (almost real-time) optimization is desirable. We use the Cimmino algorithm because it is fast, linear, and always converges reliably. A phase I motexafin lutetium (MLu)-mediated photodynamic therapy (PDT) protocol is on-going at the University of Pennsylvania. The standard plan for the protocol uses equal source strength and equal spaced loading (1-cm). PDT for the prostate is performed with cylindrical diffusing fibers (CDF) of various lengths inserted to longitudinal coverage within the matrix of parallel catheters perpendicular to a base plate. We developed several search procedures to aid the user in choosing the positions, lengths, and intensities of the CDFs. The Cimmino algorithm is used in these procedures to optimize the strengths of the light catheters at each step of the iterative selection process. Maximum and minimum bounds on allowed doses to points in four volumes (prostate, urethra, rectum, and background) constrain the solutions for the strengths of the linear light sources. Uniform optical properties are assumed. To study how different opacities of the prostate would affect optimization, optical kernels of different light penetration were used. Another goal is to see whether the urethra and rectum can be spared, with minimal effect on PTV treatment delivery, by manipulating light illumination times of the sources. Importance weights are chosen beforehand for organ volumes, and normalized. Compared with the standard plan, our algorithm is shown to produce a plan that better spares the urethra and rectum and is very fast. Thus the combined selection of positions, lengths, and strengths of interstitial light sources improves outcome. PMID- 26136613 TI - In vivo measurement of fluorescence emission in the human prostate during photodynamic therapy. AB - Among the challenges to the clinical implementation of photodynamic therapy (PDT) is the delivery of a uniform photodynamic dose to induce uniform damage to the target tissue. As the photodynamic dose depends on both the local sensitizer concentration and the local fluence rate of treatment light, knowledge of both of these factors is essential to the delivery of uniform dose. In this paper, we investigate the distribution and kinetics of the photosensitizer motexafin lutetium (MLu, Lutrin(r)) as revealed by its fluorescence emission. Our current prostate treatment protocol involves interstitial illumination of the organ via cylindrical diffusing fibers (CDF's) inserted into the prostate though clear catheters. For planning and treatment purposes, the prostate is divided into 4 quadrants. We use one catheter in each quadrant to place an optical fiber-based fluorescence probe into the prostate. This fiber is terminated in a beveled tip, allowing it to deliver and collect light perpendicular to the fiber axis. Excitation light is provided by a 465 nm light emitting diode (LED) source coupled to a dichroic beamsplitter, which passes the collected fluorescence emission to a CCD spectrograph. Spectra are obtained before and after PDT treatment in each quadrant of the prostate and are analyzed via a linear fitting algorithm to separate the MLu fluorescence from the background fluorescence originating in the plastic catheter. A computer-controlled step motor allows the excitation/detection fiber to be moved along the catheter, building up a linear profile of the fluorescence emission spectrum of the tissue as a function of position. We have analyzed spectral fluorescence profiles obtained in 4 patients before and after MLu-mediated PDT. We find significant variation both within individual prostates and among patients. Within a single quadrant, we have observed the fluorescence signal to change by as much as a factor of 3 over a distance of 2 cm. Comparisons of pre- and post-PDT spectra allow a quantification treatment-induced photobleaching. Like the drug distribution, the extent of photobleaching varies widely among patients. In two cases, we observed bleaching of approximately 50% of the drug, while others exhibited negligible photobleaching. PMID- 26136614 TI - A method to improve reconstruction of the distribution of hemoglobin, oxygenation, and MLu concentration in the human prostate before and after photodynamic therapy. AB - Explicit dosimetry of photodynamic therapy requires detailed knowledge of the light, drug, and oxygenation distributions within the target tissue. We present a method for the optical detection and three-dimensional reconstruction of hemoglobin concentration and oxygenation and sensitizer concentration within the human prostate. Spectrally resolved diffuse transmission measurements were made using a small isotropic fiber-based white light source and an isotropic detector inserted into the prostate via parallel closed transparent catheters. The spectra were modeled using the diffusion approximation appropriate for infinite media. The optical absorption of the prostate was assumed to be a linear combination of the absorption spectra of oxy- and deoxyhemoglobin and MLu, and the scattering was assumed to be of the form A(lambda/lambda0)-b. The separation of absorption and scattering coefficients was accomplished based on the spectral shape of the diffuse transmission, rather than the spatial variation in intensity. By making multiple measurements at various source-detector separations, we investigate the signal-to-noise sensitivity of our algorithm. In addition, the redundancy in our source-detector position matrix creates several positions in which the tissue parameters can be reconstructed from multiple independent measurements, allowing an assessment of the repeatability of the algorithm. We find significant heterogeneity in the reconstructed optical properties; however the recovery of spectrally consistent absorption and scattering spectra is improved compared to wavelength-wise reconstruction algorithms. PMID- 26136615 TI - HULC and H19 Played Different Roles in Overall and Disease-Free Survival from Hepatocellular Carcinoma after Curative Hepatectomy: A Preliminary Analysis from Gene Expression Omnibus. AB - OBJECTIVE: This study aimed to evaluate the relationships between long noncoding RNAs (lncRNAs) in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and survival. METHODS: We correlated the lncRNAs in tumor tissues with HCC survival and clinicopathological features based on Gene Expression Omnibus expression profile GSE36376. RESULTS: Eight lncRNAs and 240 HCC patients were included. Cox regression analysis indicated that HULC was a positive factor for HCC overall survival (HR = 0.885, 95% CI = 0.797-0.983, and P = 0.023) and disease-free survival time (HR = 0.913, 95% CI = 0.835-0.998, and P = 0.045). H19 and UCA1 were both demonstrated to be risk factors of HCC disease-free survival in multivariate Cox model (HR = 1.071, 95% CI = 1.01-1.137, and P = 0.022 and HR = 2.4, 95% CI = 1.092-5.273, and P = 0.029, resp.). But Kaplan-Meier method showed no significant association between UCA1 and HCC disease-free survival (log rank P = 0.616). Logistic regression demonstrated that H19 was overexpressed in HBV-infected patients (OR = 1.14, 95% CI = 1.008-1.29, and P = 0.037). HULC had a significant association with vascular invasion (OR = 0.648, 95% CI = 0.523-0.803, and P < 0.001). H19 and MEG3 were both considered to be risk factors for high AFP level (OR = 1.45, 95% CI = 1.277-1.646, and P < 0.001 and OR = 1.613, 95% CI = 1.1-2.365, and P = 0.014, resp.). CONCLUSIONS: Contributing to decreased susceptibility to vascular invasion, upregulation of HULC in tumor tissues was positively associated with HCC survival. In contrast, H19 overexpression might be risk factor for HCC aggressiveness and poor outcomes. PMID- 26136616 TI - Cellular and molecular mechanisms of negligible senescence: insight from the sea urchin. AB - Sea urchins exhibit a very different life history from humans and short-lived model animals and therefore provide the opportunity to gain new insight into the complex process of aging. Sea urchins grow indeterminately, regenerate damaged appendages, and reproduce throughout their lifespan. Some species show no increase in mortality rate at advanced ages. Nevertheless, different species of sea urchins have very different reported lifespans ranging from 4 to more than 100 years, thus providing a unique model to investigate the molecular, cellular, and physiological mechanisms underlying both lifespan determination and negligible senescence. Studies to date have demonstrated maintenance of telomeres, maintenance of antioxidant and proteasome enzyme activities, and little accumulation of oxidative cellular damage with age in tissues of sea urchin species with different lifespans. Gene expression studies indicate that key cellular pathways involved in energy metabolism, protein homeostasis, and tissue regeneration are maintained with age. Taken together, these studies suggest that long-term maintenance of mechanisms that sustain tissue homeostasis and regenerative capacity is essential for indeterminate growth and negligible senescence, and a better understanding of these processes may suggest effective strategies to mitigate the degenerative decline in human tissues with age. PMID- 26136617 TI - Independent chemical regulation of health and senescent spans in Drosophila. AB - Curcumin feeding of Drosophila larvae or young adults inhibits TOR and other known longevity genes and induces an extended health span in a normal-lived Ra strain adult. Combining larval curcumin feeding with an adult dietary restriction (DR) diet does not yield an additive effect. The age-specific mortality rate is decreased and is comparable with that of genetically selected long-lived La animals. Feeding Ra adults with the drug their whole life, or only during the senescent span, results in a weak negative effect on median longevity with no increase in maximum lifespan. The La strain shows no response to this DR mimetic. Thus, curcumin acts in a life stage-specific manner to extend the health span. Histone deacetylase inhibitors decrease the longevity of Ra animals if administered over the health span only or over the entire adult lifespan, but these inhibitors increase longevity when administered in the transition or senescent spans. Their major effect is a reduction in the mortality rate of older flies, raising the possibility of reducing frailty in older organisms. Their life stage-specific effects are complementary to that of curcumin. Use of stage specific drugs may enable targeted increases in health or senescent spans, and thus selectively increase the quality of life. PMID- 26136618 TI - Botryllus schlosseri, an emerging model for the study of aging, stem cells, and mechanisms of regeneration. AB - The decline of tissue regenerative potential with the loss of stem cell function is a hallmark of mammalian aging. We study Botryllus schlosseri, a colonial chordate which exhibits robust stem cell-mediated regeneration capacities throughout life. Larvae, derived by sexual reproduction and chordate development, metamorphose to clonal founders that undergo weekly formation of new individuals by budding from stem cells. Individuals are transient structures which die through massive apoptosis, and successive buds mature to replicate an entire new body. As a result, their stem cells, which are the only self-renewing cells in a tissue, are the only cells which remain through the entire life of the genotype and retain the effects of time. During aging, a significant decrease in the colonies' regenerative potential is observed and both sexual and asexual reproductions will eventually halt. When a parent colony is experimentally separated into a number of clonal replicates, they frequently undergo senescence simultaneously, suggesting a heritable factor that determines lifespan in these colonies. The availability of the recently published B. schlosseri genome coupled with its unique life cycle features promotes the use of this model organism for the study of the evolution of aging, stem cells, and mechanisms of regeneration. PMID- 26136619 TI - Hydra as a tractable, long-lived model system for senescence. AB - Hydra represents a unique model system for the study of senescence, with the opportunity for the comparison of non-aging and induced senescence. Hydra maintains three stem cell lineages, used for continuous tissue morphogenesis and replacement. Recent work has elucidated the roles of the insulin/IGF-1 signaling target FoxO, of Myc proteins, and of PIWI proteins in Hydra stem cells. Under laboratory culture conditions, Hydra vulgaris show no signs of aging even under long-term study. In contrast, Hydra oligactis can be experimentally induced to undergo reproduction-associated senescence. This provides a powerful comparative system for future studies. PMID- 26136620 TI - Aging in the colonial chordate, Botryllus schlosseri. AB - What mechanisms underlie aging? One theory, the wear-and-tear model, attributes aging to progressive deterioration in the molecular and cellular machinery which eventually lead to death through the disruption of physiological homeostasis. The second suggests that life span is genetically programmed, and aging may be derived from intrinsic processes which enforce a non-random, terminal time interval for the survivability of the organism. We are studying an organism that demonstrates both properties: the colonial ascidian, Botryllus schlosseri. Botryllus is a member of the Tunicata, the sister group to the vertebrates, and has a number of life history traits which make it an excellent model for studies on aging. First, Botryllus has a colonial life history, and grows by a process of asexual reproduction during which entire bodies, including all somatic and germline lineages, regenerate every week, resulting in a colony of genetically identical individuals. Second, previous studies of lifespan in genetically distinct Botryllus lineages suggest that a direct, heritable basis underlying mortality exists that is unlinked to reproductive effort and other life history traits. Here we will review recent efforts to take advantage of the unique life history traits of B. schlosseri and develop it into a robust model for aging research. PMID- 26136621 TI - Exploring the physiology and pathology of aging in the intestine of Drosophila melanogaster. AB - The gastrointestinal tract, due to its role as a digestive organ and as a barrier between the exterior and interior milieus, is critically impacted by dietary, environmental, and inflammatory conditions that influence health and lifespan. Work in flies is now uncovering the multifaceted molecular mechanisms that control homeostasis in this tissue, and establishing its central role in health and lifespan of metazoans. The Drosophila intestine has thus emerged as a productive, genetically accessible model to study various aspects of the pathophysiology of aging. Studies in flies have characterized the maintenance of regenerative homeostasis, the development of immune senescence, the loss of epithelial barrier function, the decline in metabolic homeostasis, as well as the maintenance of epithelial diversity in this tissue. Due to its fundamental similarity to vertebrate intestines, it can be anticipated that findings obtained in this system will have important implications for our understanding of age related changes in the human intestine. Here, I review recent studies exploring age-related changes in the fly intestine, and their insight into the regulation of health and lifespan of the animal. PMID- 26136622 TI - Using C. elegans for aging research. AB - Over a century ago, the zoologist Emile Maupas first identified the nematode, Rhabditis elegans, in the soil in Algiers. Subsequent work and phylogenic studies renamed the species Caenorhabditis elegans or more commonly referred to as C. elegans; (Caeno meaning recent; rhabditis meaning rod; elegans meaning nice). However, it was not until 1963, when Sydney Brenner, already successful from his work on DNA, RNA, and the genetic code, suggested the future of biological research lay in model organisms. Brenner believed that biological research required a model system that could grow in vast quantities in the lab, were cheap to maintain and had a simple body plan, and he chose the nematode C. elegans to fulfill such a role. Since that time, C. elegans has emerged as one of the premiere model systems for aging research. This paper reviews some initial identification of mutants with altered lifespan with a focus on genetics and then discusses advantages and disadvantages for using C. elegans as a model system to understand human aging. This review focuses on molecular genetics aspects of this model organism. PMID- 26136623 TI - Indentation experiments and simulation of ovine bone using a viscoelastic-plastic damage model. AB - Indentation methods have been widely used to study bone at the micro- and nanoscales. It has been shown that bone exhibits viscoelastic behavior with permanent deformation during indentation. At the same time, damage due to microcracks is induced due to the stresses beneath the indenter tip. In this work, a simplified viscoelastic-plastic damage model was developed to more closely simulate indentation creep data, and the effect of the model parameters on the indentation curve was investigated. Experimentally, baseline and 2-year postovariectomized (OVX-2) ovine (sheep) bone samples were prepared and indented. The damage model was then applied via finite element analysis to simulate the bone indentation data. The mechanical properties of yielding, viscosity, and damage parameter were obtained from the simulations. The results suggest that damage develops more quickly for OVX-2 samples under the same indentation load conditions as the baseline data. PMID- 26136624 TI - Predicting Early Bulbar Decline in Amyotrophic Lateral Sclerosis: A Speech Subsystem Approach. AB - PURPOSE: To develop a predictive model of speech loss in persons with amyotrophic lateral sclerosis (ALS) based on measures of respiratory, phonatory, articulatory, and resonatory functions that were selected using a data-mining approach. METHOD: Physiologic speech subsystem (respiratory, phonatory, articulatory, and resonatory) functions were evaluated longitudinally in 66 individuals with ALS using multiple instrumentation approaches including acoustic, aerodynamic, nasometeric, and kinematic. The instrumental measures of the subsystem functions were subjected to a principal component analysis and linear mixed effects models to derive a set of comprehensive predictors of bulbar dysfunction. These subsystem predictors were subjected to a Kaplan-Meier analysis to estimate the time until speech loss. RESULTS: For a majority of participants, speech subsystem decline was detectible prior to declines in speech intelligibility and speaking rate. Among all subsystems, the articulatory and phonatory predictors were most responsive to early bulbar deterioration; and the resonatory and respiratory predictors were as responsive to bulbar decline as was speaking rate. CONCLUSIONS: The articulatory and phonatory predictors are sensitive indicators of early bulbar decline due to ALS, which has implications for predicting disease onset and progression and clinical management of ALS. PMID- 26136625 TI - Abnormal Olfaction in Parkinson's Disease Is Related to Faster Disease Progression. AB - INTRODUCTION: A possible association between olfactory dysfunction and Parkinson's disease (PD) severity has been a topic of contention for the past 40 years. Conflicting reports may be partially explained by procedural differences in olfactory assessment and motor symptom evaluation. METHODS: One hundred and sixty-six nondemented PD patients performed the Brief-Smell Identification Test and test scores below the estimated 20th percentile as a function of sex, age, and education (i.e., 80% specificity) were considered demographically abnormal. Patients underwent motor examination after 12 h without antiparkinsonian medication. RESULTS: Eighty-two percent of PD patients had abnormal olfaction. Abnormal performance on the Brief-Smell Identification Test was associated with higher disease severity (i.e., Hoehn and Yahr, Unified Parkinson's Disease Rating Scale-III, Freezing of Gait questionnaire, and levodopa equivalent dose), even when disease duration was taken into account. CONCLUSIONS: Abnormal olfaction in PD is associated with increased severity and faster disease progression. PMID- 26136627 TI - Spirometric values and chest pain intensity three days post-operative coronary artery bypass graft surgery. AB - AIM: Coronary artery bypass graft surgery (CABG) is proved to have ventilatory complications and reduction in spirometric values. This study aimed to examine the hypothesis that reduction of post-operative chest pain intensity would be associated with improvement in the spirometric values for patient underwent CABG. MATERIALS AND METHOD: 26 cardiac patients recruited for this study. Their convenience to the study inclusion criteria decided their eligibility. Through 3 days after elective CABG their spirometric values were measured along with their perception to chest pain intensity using 0-10 numeric rating scale. Collected data were recorded and analyzed statistically. RESULTS: Chest pain intensity showed progressive significant (P = 0.0001) reduction through the 3 days post operative. On the other hand spirometric values also showed progressive improvement through the 3 days post-operative. This improvement was significant for all measured spirometric values except for the ratio of forced expiratory volume in the 1st second to the forced vital capacity (P = 0.134). There was no significant relationship between the chest pain intensity and spirometric values. This was applied to all measured spirometric values and to the 3 days postoperative. CONCLUSION: The current study findings rejected the examined hypothesis that reduction of post-operative chest pain intensity would be associated with improvement in the spirometric values for patient underwent coronary artery bypass graft surgery. There was no significant relationship between the chest pain intensity and any of the spirometric values at any of the 3 post-operative days. PMID- 26136626 TI - Cross Talk between Proliferative, Angiogenic, and Cellular Mechanisms Orchestred by HIF-1alpha in Psoriasis. AB - Psoriasis is a chronic inflammatory skin disease where the altered regulation in angiogenesis, inflammation, and proliferation of keratinocytes are the possible causes of the disease, and the transcription factor "hypoxia-inducible factor 1 alpha" (HIF-1alpha) is involved in the homeostasis of these three biological phenomena. In this review, the role of HIF-1alpha in the cross talk between the cytokines and cells of the immunological system involved in the pathogenesis of psoriasis is discussed. PMID- 26136628 TI - The platelet-to-lymphocyte ratio as a predictor of all-cause mortality in patients with coronary artery disease undergoing elective percutaneous coronary intervention and stent implantation. AB - BACKGROUND: There is no data regarding the association between the platelet-to lymphocyte ratio (PLR) and long-term mortality in patients with stable coronary artery disease (SCAD). The aim of this study is to evaluate the utility of the pre-procedural PLR for predicting long-term, all-cause mortality in patients with SCAD undergoing percutaneous coronary intervention (PCI) and stent implantation. METHODS: We analyzed a total of 2959 consecutive patients with SCAD who underwent PCI (balloon angioplasty followed by stent implantation or direct stenting) between July 2006 and December 2011 at our institution. The patients were stratified into tertiles according to their admission PLR. The association between the PLR value and the outcomes was assessed using Cox proportional regression analysis after adjusting for clinical angiographic and laboratory data. RESULTS: During median follow-up of 1124 days, mortality was highest in patients with PLR within the 3rd tertile as compared to the 2nd and the 1st tertile (11.0% vs 8.7% vs. 9.6%, respectively, p = 0.03). PLR remained associated with mortality in multivariable analysis including clinical variables, ejection fraction and angiographic parameters HR (per 10 units increase) = 1.02 [95%CI,1.01 / 1.04, p = 0.006]. After adjustment for the eGFR and hemoglobin levels, PLR was however no longer significantly associated with mortality. CONCLUSION: PLR has potential predictive value in patients with SCAD, which has not been reported previously, but statistical significance disappears after adjusting for estimated glomerular filtration rate (eGFR) and hemoglobin levels as a potential confounding variable. PMID- 26136629 TI - Prediction of 10-year risk of hard coronary events among Saudi adults based on prevalence of heart disease risk factors. AB - AIM: Cardiovascular disease is becoming the lead cause of mortality and morbidity worldwide, and developing countries are the main contributors to this trend. Saudi Arabia, which is considered a rapidly developing country, faces progressive urbanization and the adoption of a westernized lifestyle, factors which contribute to the rising burden of cardiovascular disease. Our study evaluates the prevalence of coronary risk factors and predicts hard coronary artery events over 10 years in an urban Saudi cohort. METHODS: A cross-sectional observational study was conducted on a Saudi population. The study involved Saudi subjects aged more than 20 years without a history of coronary heart disease. Demographic variables and hard coronary events (HCE) risk factors were measured. Each subject's 10-year HCE risk was estimated by means of the Framingham Risk Score (FRS). RESULTS: A total of 4932 subjects (2215 men and 2717 women) were examined, the majority (85%) of whom were less than 40 years old. The risk of developing HCE within the next 10 years was low in 92.6% of subjects, intermediate in 3.2% and high in 4.1%. On considering diabetes as coronary heart disease (CHD) risk equivalent, 26% of subjects were at high risk for hard coronary events in 10 years. The HCE risk progressively increased with age and was higher in men. CONCLUSIONS: Our study, the first to estimate the 10-year risk of HCE among adults in an emerging country, determined that a significant proportion of a younger aged population is at risk for the development of hard coronary events. Public awareness programs to control risk factors are warranted. PMID- 26136630 TI - Coronary artery ectasia - A sample from Saudi Arabia. AB - INTRODUCTION: Coronary artery ectasia is an uncommon disease that has been increasingly noticed as the increase in utilization of coronary angiograms. The aim of this study is to characterize coronary artery ectasia in the population of Saudi Arabia. METHODS: This is a retrospective study involved all patient with invasive coronary angiogram that was done at a tertiary hospital in Saudi Arabia from January 2011 to December 2013. RESULTS: A total of 1115 coronary angiograms were reviewed. Coronary artery ectasia was found in 67 patients (6% of all coronary angiograms). The right coronary artery was involved in 73% of cases. And 43% of the cases had severe ectasia. CONCLUSION: The prevalence of coronary artery ectasia in Saudi Arabia among patient who went for coronary angiography is higher than what has been published in previous studies and a significant number of patients have severe disease. PMID- 26136631 TI - Atrioventricular block during fetal life. AB - Congenital complete atrioventricular (AV) block occurs in approximately 1 in 20,000 live births and is known to result in significant mortality and morbidity both during fetal life and postnatally. Complete AV block can occur as a result of an immune or a non-immune mediated process. Immune mediated AV block is a multifactorial disease, but is associated with the trans-placental passage of maternal autoantibodies (anti-Ro/SSA and/or anti-La/SSB). These autoantibodies attach to and subsequently damage the cardiomyocytes and conduction tissue in susceptible fetuses. In this report, we examine the evidence in reference to means of assessment, pathophysiology, and potential prenatal therapy of atrioventricular block. PMID- 26136632 TI - Primary prevention with statins in cardiovascular diseases: A Saudi Arabian perspective. AB - Cardiovascular disease (CVD) constitutes one of the major causes of deaths and disabilities, globally claiming 17.3 million lives a year. Incidence of CVD is expected to rise to 25 million by 2030, and Saudi Arabia, already witnessing a rapid rise in CVDs, is no exception. Statins are the drugs of choice in established CVDs. In the recent past, evidence was increasingly suggesting benefits in primary prevention. But over the last decade Saudi Arabia has a witnessed significant rise in CVD-related deaths. Smoking, high-fat, low-fiber dietary intake, lack of exercise, sedentary life, high blood cholesterol and glucose levels were reported as frequent CVD-risk factors among Saudis, who may therefore be considered for primary prevention with statin. The prevalence of dyslipidemia, in particular, indicates that treatment should be directed at reducing the disorder with lipid-modifying agents and therapeutic lifestyle changes. The recent American College of Cardiology (ACC)/American Heart Association (AHA) guidelines has reported lowering the low-density lipoprotein cholesterol (LDL-C) target levels, prescribed by the 2011 European Society of Cardiology (ESC)/the European Atherosclerosis Society (EAS). The new ACC/AHA guidelines have overemphasized the use of statin while ignoring lipid targets, and have recommended primary prevention with moderate-intensity statin to individuals with diabetes aged 40-75 years and with LDL-C 70-189 mg/dL. Treatment with statin was based on estimated 10-year atherosclerotic-CVD (ASCVD) risk in individuals aged 40-75 years with LDL-C 70 to 189 mg/dL and without clinical ASCVD or diabetes. Adoption of the recent ACC/AHA guidelines will lead to inclusion of a large population for primary prevention with statins, and would cause over treatment to some who actually would not need statin therapy but instead should have been recommended lifestyle modifications. Furthermore, adoption of this guideline may potentially increase the incidences of statin intolerance and side-effects. On the other hand, the most widely used lipid management guideline, the 2011 ESC/EAC guidelines, targets lipid levels at different stages of disease activity before recommending statins. Hence, the 2011 ESC/EAC still offers a holistic and pragmatic approach to treating lipid abnormalities in CVD. Therefore, it is the 2011 ESC/EAC guidelines, and not the recent ACC/AHA guidelines, that should be adopted to draw guidance on primary prevention of CVD in Saudi Arabia. PMID- 26136633 TI - Mechanical post-conditioning in STEMI patients undergoing primary percutaneous coronary intervention. AB - Although early myocardial reperfusion via primary percutaneous coronary intervention (PCI) allows the preservation of left ventricular function and improves outcome, the acute restoration of blood flow may contribute to the pathophysiology of infarction, a complex phenomenon called reperfusion injury. First described in animal models of coronary obstruction, mechanical post conditioning, a sequence of repetitive interruption of coronary blood flow applied immediately after reopening of the occluded vessel, was able to reduce the infarct size. However, evidence of its real benefit remains controversial. This review describes the mechanisms of post-conditioning action and the different protocols employed focusing on its impact on primary PCI outcome. PMID- 26136634 TI - Catheter ablation of atrial arrhythmias in a patient with surgically corrected congenital heart disease and inferior vena cava interruption. AB - A 15 year old girl who underwent surgical correction of ventricular septal defect and patent ductus arteriosus ligation in childhood presented with atrial tachycardia of crista terminalis origin and counterclockwise atrial flutter. She also had associated interruption of inferior vena cava which continued as azygous vein and left superior vena cava which drained via coronary sinus into the right atrium. She underwent radiofrequency ablation of both the tachycardias via internal jugular vein and azygous vein approach using 3D electroanatomical mapping system. PMID- 26136635 TI - Hypertrophic cardiomyopathy masquerading as infiltrative restrictive cardiomyopathy and refractory congestive failure-resolution with catheter ablation of atrial flutter - A case report. AB - We report a case of a young male presenting as Restrictive cardiomyopathy, refractory heart failure and syncope due to typical right atrial flutter complicating hypertrophic cardiomyopathy. Successful catheter ablation of the flutter promptly ameliorated the congestive failure with resolution of restrictive physiology. PMID- 26136636 TI - Splenic abscess associated with infective endocarditis; Case series. AB - Splenic abscess is a well-described but rare complication of infective endocarditis. Rapid diagnosis and treatment are essential as its course can be fatal. We present three case reports that describe the management of splenic abscesses in patients initially diagnosed with infective endocarditis. In all cases, the diagnosis was based on the findings of abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI). In two of the cases, splenectomy was performed before valve surgery; while in the third case, the spleen was removed after cardiac surgery. All three patients recovered fully, with satisfactory follow-up as outpatients. Immediate splenectomy, combined with appropriate antibiotics and valve replacement surgery alongside multi disciplinary team work could be the treatment of choice in this clinical scenario. PMID- 26136637 TI - Coronary perforation with tamponade successfully managed by retrograde and antegrade coil embolization. AB - In recent years, retrograde approach for chronic total occlusions has rapidly evolved, enabling a higher rate of revascularization success. Compared to septal channels, epicardial collaterals tend to be more tortuous, more difficult to negotiate, and more prone to rupture. Coronary perforation is a rare but potentially life-threatening complication of coronary angioplasty, often leading to emergency cardiac surgery. We report a case of a retrograde chronic total occlusion revascularization through epicardial collaterals, complicated by both retrograde and antegrade coronary perforation with tamponade, and successfully managed by coil embolization. PMID- 26136638 TI - Subclinical atherosclerosis in patients with psoriasis. PMID- 26136639 TI - N-terminal pro brain natriuretic peptide in coronary artery disease. PMID- 26136640 TI - Reply to: N-terminal pro brain natriuretic peptide in coronary artery disease. PMID- 26136641 TI - Analyzing the gene expression profile of anaplastic histology Wilms' tumor with real-time polymerase chain reaction arrays. AB - BACKGROUND: Wilms' tumor (WT) is one of the most common malignant neoplasms of the urinary tract in children. Anaplastic histology (unfavorable histology) accounts for about 10% of whole WTs, and it is the single most important histologic predictor of treatment response and survival in patients with WT; however, until now the molecular basis of this phenotype is not very clearly. METHODS: A real-time polymerase chain reaction (PCR) array was designed and tested. Next, the gene expression profile of pediatric anaplastic histology WT and normal adjacent tissues were analyzed. These expression data were anlyzed with Multi Experiment View (MEV) cluster software further. Datasets representing genes with altered expression profiles derived from cluster analyses were imported into the Ingenuity Pathway Analysis Tool (IPA). RESULTS: 88 real-time PCR primer pairs for quantitative gene expression analysis of key genes involved in pediatric anaplastic histology WT were designed and tested. The gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal controls; we identified 15 genes that are up regulated and 16 genes that are down-regulated in the former. To investigate biological interactions of these differently regulated genes, datasets representing genes with altered expression profiles were imported into the IPA for further analysis, which revealed three significant networks: Cancer, Hematological Disease, and Gene Expression, which included 27 focus molecules and a significance score of 43. The IPA analysis also grouped the differentially expressed genes into biological mechanisms related to Cell Death and Survival 1.15E(-12), Cellular Development 2.84E(-11), Cellular Growth and Proliferation 2.84E(-11), Gene Expression 4.43E(-10), and DNA Replication, Recombination, and Repair 1.39E(-07). The important upstream regulators of pediatric anaplastic histology WT were TP53 and TGFbeta1 signaling (P = 1.15E(-14) and 3.79E(-13), respectively). CONCLUSIONS: Our study demonstrates that the gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal tissues with real-time PCR array. We identified some genes that are dysregulated in pediatric anaplastic histology WT for the first time, such as HDAC7, and IPA analysis showed the most important pathways for pediatric anaplastic histology WT are TP53 and TGFbeta1 signaling. This work may provide new clues into the molecular mechanisms behind pediatric anaplastic histology WT. PMID- 26136642 TI - Pathological features of transplanted tumor established by CD133 positive TJ905 glioblastoma stem-like cells. AB - BACKGROUND: This study is to explore the pathological features of transplanted tumor established by CD133 positive TJ905 glioblastoma stem-like cells. METHODS: CD133 positive TJ905 glioma cells were separated by immunomagnetic beads to isolate glioma stem-like cells. TJ905 cells and stem-like cells were inoculated subcutaneously into the mice to establish model of transplanted tumor, respectively. Mice growing condition and behavior were observed. HE staining assay, immunohistochemical assay for GFAP, Ki-67 and Olig-2, and CD34 marked microvascular density (MVD) test were performed. RESULTS: The growing condition and behavior of mice in TJ905 stem cell group was more exaggerated and the models showed stronger malignant features pathologically than that in TJ905 cell group. Glial fibrillary acidic protein (GFAP) in TJ905 cell and stem-like cell group showed the transplanted tumor originated from astrocytes. Expression of Ki-67 and oligodendrocyte transcription factor-2 (Olig-2) in TJ905 stem cells was higher notably and CD34 expression in stem cell group was significantly higher than that in the other two groups. CONCLUSIONS: Pathological features of transplanted tumor established by CD133 positive glioblastoma stem-like cells show more malignant. Use of TJ905 stem cells to establish transplanted tumor model in nude mice is excellent for glioma research. PMID- 26136643 TI - Increased expression of the NLRP3 inflammasome components in patients with Behcet's disease. AB - BACKGROUND: Behcet's disease (BD) is a systemic inflammatory disease with manifestations including recurrent oral and genital ulcerations, and vasculitis involving the skin, mucosa, joints, eyes, veins, arteries, nervous and gastrointestinal systems. BD is seen as a disease at the crossroad between autoimmune and autoinflammatory syndromes, possibly triggered by an aberrant response to infectious stimuli. The relevance of Gram negative bacteria-mediated oral inflammation with the increased expression of NACHT, LRR, and PYD domains containing protein 3 (NLRP3), leading to systemic inflammation, prompted us to investigate the expression of NLRP3 inflammasome components and its link with IL 1beta hypersecretion. FINDINGS: When peripheral blood mononuclear cells (PBMCs) from 15 active, 15 stable BD patients and 15 healthy volunteers were stimulated, the basal and LPS-induced expressions of NLRP3 inflammasome components were significantly increased at both mRNA and protein levels in BD patients compared to healthy controls. Also, increased expression of NLRP3 and ASC was observed in 25 BD skin lesions compared to 25 erythema nodosum patients. Compatible with this, secretion of IL-1beta by PBMCs stimulated with LPS alone or LPS plus ATP was increased in BD compared to healthy controls, which was suppressed by caspase 1 inhibitor. CONCLUSION: Our findings suggest the possible link between increased IL-1beta secretion and increased expression of NLRP3 inflammasome components in BD patients with skin manifestations. PMID- 26136644 TI - Neural mechanisms of social dominance. AB - In a group setting, individuals' perceptions of their own level of dominance or of the dominance level of others, and the ability to adequately control their behavior based on these perceptions are crucial for living within a social environment. Recent advances in neural imaging and molecular technology have enabled researchers to investigate the neural substrates that support the perception of social dominance and the formation of a social hierarchy in humans. At the systems' level, recent studies showed that dominance perception is represented in broad brain regions which include the amygdala, hippocampus, striatum, and various cortical networks such as the prefrontal, and parietal cortices. Additionally, neurotransmitter systems such as the dopaminergic and serotonergic systems, modulate and are modulated by the formation of the social hierarchy in a group. While these monoamine systems have a wide distribution and multiple functions, it was recently found that the Neuropeptide B/W contributes to the perception of dominance and is present in neurons that have a limited projection primarily to the amygdala. The present review discusses the specific roles of these neural regions and neurotransmitter systems in the perception of dominance and in hierarchy formation. PMID- 26136645 TI - Subchronic toxicity study of standardized methanolic extract of Mitragyna speciosa Korth in Sprague-Dawley Rats. AB - Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days). Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardized methanolic extract of ketum (SMEMS) in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for hematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals. PMID- 26136646 TI - Multidimensional frequency domain analysis of full-volume fMRI reveals significant effects of age, gender, and mental illness on the spatiotemporal organization of resting-state brain activity. AB - Clinical research employing functional magnetic resonance imaging (fMRI) is often conducted within the connectionist paradigm, focusing on patterns of connectivity between voxels, regions of interest (ROIs) or spatially distributed functional networks. Connectivity-based analyses are concerned with pairwise correlations of the temporal activation associated with restrictions of the whole-brain hemodynamic signal to locations of a priori interest. There is a more abstract question however that such spatially granular correlation-based approaches do not elucidate: Are the broad spatiotemporal organizing principles of brains in certain populations distinguishable from those of others? Global patterns (in space and time) of hemodynamic activation are rarely scrutinized for features that might characterize complex psychiatric conditions, aging effects or gender among other variables of potential interest to researchers. We introduce a canonical, transparent technique for characterizing the role in overall brain activation of spatially scaled periodic patterns with given temporal recurrence rates. A core feature of our technique is the spatiotemporal spectral profile (STSP), a readily interpretable 2D reduction of the native four-dimensional brain * time frequency domain that is still "big enough" to capture important group differences in globally patterned brain activation. Its power to distinguish populations of interest is demonstrated on a large balanced multi-site resting fMRI dataset with nearly equal numbers of schizophrenia patients and healthy controls. Our analysis reveals striking differences in the spatiotemporal organization of brain activity that correlate with the presence of diagnosed schizophrenia, as well as with gender and age. To the best of our knowledge, this is the first demonstration that a 4D frequency domain analysis of full volume fMRI data exposes clinically or demographically relevant differences in resting state brain function. PMID- 26136647 TI - Aberrant insulin signaling in Alzheimer's disease: current knowledge. AB - Alzheimer's disease (AD) is the most common form of dementia affecting elderly people. AD is a multifaceted pathology characterized by accumulation of extracellular neuritic plaques, intracellular neurofibrillary tangles (NFTs) and neuronal loss mainly in the cortex and hippocampus. AD etiology appears to be linked to a multitude of mechanisms that have not been yet completely elucidated. For long time, it was considered that insulin signaling has only peripheral actions but now it is widely accepted that insulin has neuromodulatory actions in the brain. Insulin signaling is involved in numerous brain functions including cognition and memory that are impaired in AD. Recent studies suggest that AD may be linked to brain insulin resistance and patients with diabetes have an increased risk of developing AD compared to healthy individuals. Indeed insulin resistance, increased inflammation and impaired metabolism are key pathological features of both AD and diabetes. However, the precise mechanisms involved in the development of AD in patients with diabetes are not yet fully understood. In this review we will discuss the role played by aberrant brain insulin signaling in AD. In detail, we will focus on the role of insulin signaling in the deposition of neuritic plaques and intracellular NFTs. Considering that insulin mitigates beta amyloid deposition and phosphorylation of tau, pharmacological strategies restoring brain insulin signaling, such as intranasal delivery of insulin, could have significant therapeutic potential in AD treatment. PMID- 26136648 TI - Gene expression patterns and environmental enrichment-induced effects in the hippocampi of mice suggest importance of Lsamp in plasticity. AB - Limbic system associated membrane protein (Lsamp) gene is involved in behavioral adaptation in social and anxiogenic environments and has been associated with a broad spectrum of psychiatric diseases. Here we studied the activity of alternative promoters of Lsamp gene in mice in three rearing conditions (standard housing, environmental enrichment and social isolation) and in two different genetic backgrounds (129S6/SvEv and C57BL/6). Isolation had no effect on the expression levels of Lsamp. Environmental enrichment elevated the expression levels of Lsamp 1b transcript specifically in the hippocampus in B6 mice, and the same tendency existed across both mouse lines and both transcripts. Furthermore, we showed that the density of cells exhibiting 1b promoter activity is remarkably higher in the subgranular zone of the dentate gyrus in the hippocampal formation which is a specific area of enrichment-induced neurogenesis in adult rodents. On the contrary to 1b, 1a promoter is selectively active in the pyramidal and granule cell layers. We provide evidence that Lsamp modulates enrichment-induced activation of Bdnf as the enrichment-induced elevation of Bdnf in the hippocampus is significantly diminished in Lsamp-deficient mice; furthermore, a significant correlation was found between the expression levels of Lsamp and Bdnf transcripts in the hippocampus and frontal cortex. Significant strain differences in Lsamp expression were detected in the hippocampus, frontal cortex and thalamus that could be related to the different behavioral phenotype of B6 and 129Sv mice. Our data provides further evidence that LSAMP is implicated in the hippocampal connectivity and plasticity thereby modulating adaptability in changing environments. PMID- 26136650 TI - Multi-time resolution analysis of speech: evidence from psychophysics. AB - How speech signals are analyzed and represented remains a foundational challenge both for cognitive science and neuroscience. A growing body of research, employing various behavioral and neurobiological experimental techniques, now points to the perceptual relevance of both phoneme-sized (10-40 Hz modulation frequency) and syllable-sized (2-10 Hz modulation frequency) units in speech processing. However, it is not clear how information associated with such different time scales interacts in a manner relevant for speech perception. We report behavioral experiments on speech intelligibility employing a stimulus that allows us to investigate how distinct temporal modulations in speech are treated separately and whether they are combined. We created sentences in which the slow (~4 Hz; Slow) and rapid (~33 Hz; Shigh) modulations-corresponding to ~250 and ~30 ms, the average duration of syllables and certain phonetic properties, respectively-were selectively extracted. Although Slow and Shigh have low intelligibility when presented separately, dichotic presentation of Shigh with Slow results in supra-additive performance, suggesting a synergistic relationship between low- and high-modulation frequencies. A second experiment desynchronized presentation of the Slow and Shigh signals. Desynchronizing signals relative to one another had no impact on intelligibility when delays were less than ~45 ms. Longer delays resulted in a steep intelligibility decline, providing further evidence of integration or binding of information within restricted temporal windows. Our data suggest that human speech perception uses multi-time resolution processing. Signals are concurrently analyzed on at least two separate time scales, the intermediate representations of these analyses are integrated, and the resulting bound percept has significant consequences for speech intelligibility-a view compatible with recent insights from neuroscience implicating multi-timescale auditory processing. PMID- 26136649 TI - Neuron-based heredity and human evolution. AB - It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use) strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse) leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes in line with Neolamarckian concepts of evolution (Packard, 1901). Evidence is presented of bipartite evolutionary processes-Darwinian and Neolamarckian-driving human descent from a common ancestor shared with the great apes. PMID- 26136652 TI - Inhibition of multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme. AB - Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with extremely poor prognostic outcome despite intensive treatment. All chemotherapeutic agents currently used have no greater than 30-40% response rate, many fall into the range of 10-20%, with delivery across the blood brain barrier (BBB) or chemoresistance contributing to the extremely poor outcomes despite treatment. Increased expression of the multidrug resistance protein 1(MRP1) in high grade glioma, and it's role in BBB active transport, highlights this member of the ABC transporter family as a target for improving drug responses in GBM. In this study we show that small molecule inhibitors and gene silencing of MRP1 had a significant effect on GBM cell response to temozolomide (150 MUM), vincristine (100 nM), and etoposide (2 MUM). Pre-treatment with Reversan (inhibitor of MRP1 and P-glycoprotein) led to a significantly improved response to cell death in the presence of all three chemotherapeutics, in both primary and recurrent GBM cells. The presence of MK571 (inhibitor of MRP1 and multidrug resistance protein 4 (MRP4) led to an enhanced effect of vincristine and etoposide in reducing cell viability over a 72 h period. Specific MRP1 inhibition led to a significant increase in vincristine and etoposide-induced cell death in all three cell lines assessed. Treatment with MK571, or specific MRP1 knockdown, did not have any effect on temozolomide drug response in these cells. These findings have significant implications in providing researchers an opportunity to improve currently used chemotherapeutics for the initial treatment of primary GBM, and improved treatment for recurrent GBM patients. PMID- 26136651 TI - Amylin at the interface between metabolic and neurodegenerative disorders. AB - The pancreatic peptide amylin is best known for its role as a satiation hormone in the control of food intake and as the major component of islet amyloid deposits in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Epidemiological studies have established a clear association between metabolic and neurodegenerative disorders in general, and between T2DM and Alzheimer's disease (AD) in particular. Here, we discuss that amylin may be an important player acting at the interface between these metabolic and neurodegenerative disorders. Abnormal amylin production is a hallmark peripheral pathology both in the early (pre-diabetic) and late phases of T2DM, where hyperamylinemic (early phase) and hypoamylinemic (late phase) conditions coincide with hyper- and hypo-insulinemia, respectively. Moreover, there are notable biochemical similarities between amylin and beta-amyloids (Abeta), which are both prone to amyloid plaque formation and to cytotoxic effects. Amylin's propensity to form amyloid plaques is not restricted to pancreatic islet cells, but readily extends to the CNS, where it has been found to co-localize with Abeta plaques in at least a subset of AD patients. Hence, amylin may constitute a "second amyloid" in neurodegenerative disorders such as AD. We further argue that hyperamylinemic conditions may be more relevant for the early processes of amyloid formation in the CNS, whereas hypoamylinemic conditions may be more strongly associated with late stages of central amyloid pathologies. Advancing our understanding of these temporal relationships may help to establish amylin-based interventions in the treatment of AD and other neurodegenerative disorders with metabolic comorbidities. PMID- 26136653 TI - Dopamine in socioecological and evolutionary perspectives: implications for psychiatric disorders. AB - Dopamine (DA) transmission in brain areas such as the prefrontal cortex (PFC) and nucleus accumbens (NAcc) plays important roles in cognitive and affective function. As such, DA deficits have been implicated in a number of psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder (ADHD). Accumulating evidence suggests that DA is also involved in social behavior of animals and humans. Although most animals organize and live in social groups, how the DA system functions in such social groups of animals, and its dysfunction causes compromises in the groups has remained less understood. Here we propose that alterations of DA signaling and associated genetic variants and behavioral phenotypes, which have been normally considered as "deficits" in investigation at an individual level, may not necessarily yield disadvantages, but even work advantageously, depending on social contexts in groups. This hypothesis could provide a novel insight into our understanding of the biological mechanisms of psychiatric disorders, and a potential explanation that disadvantageous phenotypes associated with DA deficits in psychiatric disorders have remained in humans through evolution. PMID- 26136655 TI - Plant polyphenols as inhibitors of NF-kappaB induced cytokine production-a potential anti-inflammatory treatment for Alzheimer's disease? PMID- 26136654 TI - Noradrenergic dysfunction in Alzheimer's disease. AB - The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer's disease (AD) patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located) is a predominant site where AD-related pathology begins. Mounting evidence indicates that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed. PMID- 26136656 TI - Molecular and cellular development of spinal cord locomotor circuitry. AB - The spinal cord of vertebrate animals is comprised of intrinsic circuits that are capable of sensing the environment and generating complex motor behaviors. There are two major perspectives for understanding the biology of this complicated structure. The first approaches the spinal cord from the point of view of function and is based on classic and ongoing research in electrophysiology, adult behavior, and spinal cord injury. The second view considers the spinal cord from a developmental perspective and is founded mostly on gene expression and gain-of function and loss-of-function genetic experiments. Together these studies have uncovered functional classes of neurons and their lineage relationships. In this review, we summarize our knowledge of developmental classes, with an eye toward understanding the functional roles of each group. PMID- 26136657 TI - Extrinsic and intrinsic regulation of axon regeneration at a crossroads. AB - Repair of the injured spinal cord is a major challenge in medicine. The limited intrinsic regenerative response mounted by adult central nervous system (CNS) neurons is further hampered by astrogliosis, myelin debris and scar tissue that characterize the damaged CNS. Improved axon regeneration and recovery can be elicited by targeting extrinsic factors as well as by boosting neuron-intrinsic growth regulators. Our knowledge of the molecular basis of intrinsic and extrinsic regulators of regeneration has expanded rapidly, resulting in promising new targets to promote repair. Intriguingly certain neuron-intrinsic growth regulators are emerging as promising targets to both stimulate growth and relieve extrinsic inhibition of regeneration. This crossroads between the intrinsic and extrinsic aspects of spinal cord injury is a promising target for effective therapies for this unmet need. PMID- 26136658 TI - Lost highway(s): barriers to postnatal cortical neurogenesis and implications for brain repair. AB - The genesis of the cerebral cortex is a highly complex and tightly-orchestrated process of cell division, migration, maturation, and integration. Developmental missteps often have catastrophic consequences on cortical function. Further, the cerebral cortex, in which neurogenesis takes place almost exclusively prenatally, has a very poor capacity for replacement of neurons lost to injury or disease. A multitude of factors underlie this deficit, including the depletion of radial glia, the gliogenic switch which mitigates continued neurogenesis, diminished neuronal migratory streams, and inflammatory processes associated with disease. Despite this, there are glimmers of hope that new approaches may allow for more significant cortical repair. Herein, we review corticogenesis from the context of regeneration and detail the strategies to promote neurogenesis, including interneuron transplants and glial reprogramming. Such strategies circumvent the "lost highways" which are critical for cortical development but are absent in the adult. These new approaches may provide for the possibility of meaningful clinical regeneration of elements of cortical circuitry lost to trauma and disease. PMID- 26136659 TI - Are neural crest stem cells the missing link between hematopoietic and neurogenic niches? AB - Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system. PMID- 26136660 TI - Disruption of Slc4a10 augments neuronal excitability and modulates synaptic short term plasticity. AB - Slc4a10 is a Na(+)-coupled Cl(-)-HCO3 (-) exchanger, which is expressed in principal and inhibitory neurons as well as in choroid plexus epithelial cells of the brain. Slc4a10 knockout (KO) mice have collapsed brain ventricles and display an increased seizure threshold, while heterozygous deletions in man have been associated with idiopathic epilepsy and other neurological symptoms. To further characterize the role of Slc4a10 for network excitability, we compared input output relations as well as short and long term changes of evoked field potentials in Slc4a10 KO and wildtype (WT) mice. While responses of CA1 pyramidal neurons to stimulation of Schaffer collaterals were increased in Slc4a10 KO mice, evoked field potentials did not differ between genotypes in the stratum radiatum or the neocortical areas analyzed. Paired pulse facilitation was diminished in the hippocampus upon disruption of Slc4a10. In the neocortex paired pulse depression was increased. Though short term plasticity is modulated via Slc4a10, long term potentiation appears independent of Slc4a10. Our data support that Slc4a10 dampens neuronal excitability and thus sheds light on the pathophysiology of SLC4A10 associated pathologies. PMID- 26136661 TI - Calcium dysregulation links ALS defective proteins and motor neuron selective vulnerability. AB - More than 20 distinct gene loci have so far been implicated in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder characterized by progressive neurodegeneration of motor neurons (MN) and death. Most of this distinct set of ALS-related proteins undergoes toxic deposition specifically in MN for reasons which remain unclear. Here we overview a recent body of evidence indicative that mutations in ALS-related proteins can disrupt fundamental Ca(2+) signalling pathways in MN, and that Ca(2+) itself impacts both directly or indirectly in many ALS critical proteins and cellular processes that result in MN neurodegeneration. We argue that the inherent vulnerability of MN to dysregulation of intracellular Ca(2+) is deeply associated with discriminating pathogenicity and aberrant crosstalk of most of the critical proteins involved in ALS. Overall, Ca(2+) deregulation in MN is at the cornerstone of different ALS processes and is likely one of the factors contributing to the selective susceptibility of these cells to this particular neurodegenerative disease. PMID- 26136662 TI - Histone Acetylation Modifiers in the Pathogenesis of Alzheimer's Disease. AB - It is becoming more evident that histone acetylation, as one of the epigenetic modifications or markers, plays a key role in the etiology of Alzheimer's disease (AD). Histone acetylases and histone deacetylases (HDACs) are the well-known covalent enzymes that modify the reversible acetylation of lysine residues in histone amino-terminal domains. In AD, however, the roles of these enzymes are controversial. Some recent studies indicate that HDAC inhibitors are neuroprotective by regulating memory and synaptic dysfunctions in cellular and animal models of AD; while on the other hand, increase of histone acetylation have been implicated in AD pathology. In this review, we focus on the recent advances on the roles of histone acetylation covalent enzymes in AD and discuss how targeting these enzymes can ultimately lead to therapeutic approaches for treating AD. PMID- 26136663 TI - Role for astroglial alpha1-adrenoreceptors in gliotransmission and control of synaptic plasticity in the neocortex. AB - Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying gliotransmission remain uncertain with exocytosis being the most intriguing and debated pathway. We demonstrate that astroglial alpha1-adrenoreceptors are very sensitive to noradrenaline (NA) and make a significant contribution to intracellular Ca(2+) signaling in layer 2/3 neocortical astrocytes. We also show that astroglial alpha1-adrenoreceptors are prone to desensitization upon prolonged exposure to NA. We show that within neocortical slices, alpha-1adrenoreceptors can activate vesicular release of ATP and D-serine from cortical astrocytes which initiate a burst of ATP receptor-mediated currents in adjacent pyramidal neurons. These purinergic currents can be inhibited by intracellular perfusion of astrocytes with Tetanus Toxin light chain, verifying their origin via astroglial exocytosis. We show that alpha1 adrenoreceptor-activated release of gliotransmitters is important for the induction of synaptic plasticity in the neocortex:long-term potentiation (LTP) of neocortical excitatory synaptic potentials can be abolished by the selective alpha1-adrenoreceptor antagonist terazosin. We show that weak sub-threshold theta-burst stimulation (TBS) can induce LTP when astrocytes are additionally activated by 1 MUM NA. This facilitation is dependent on the activation of neuronal ATP receptors and is abolished in neocortical slices from dn-SNARE mice which have impaired glial exocytosis. Importantly, facilitation of LTP by NA can be significantly reduced by perfusion of individual astrocytes with Tetanus Toxin. Our results strongly support the physiological importance of astroglial adrenergic signaling and exocytosis of gliotransmitters for modulation of synaptic transmission and plasticity. PMID- 26136664 TI - Potential roles of the interaction between model V1 neurons with orientation selective and non-selective surround inhibition in contour detection. AB - Both the neurons with orientation-selective and with non-selective surround inhibition have been observed in the primary visual cortex (V1) of primates and cats. Though the inhibition coming from the surround region (named as non classical receptive field, nCRF) has been considered playing critical role in visual perception, the specific role of orientation-selective and non-selective inhibition in the task of contour detection is less known. To clarify above question, we first carried out computational analysis of the contour detection performance of V1 neurons with different types of surround inhibition, on the basis of which we then proposed two integrated models to evaluate their role in this specific perceptual task by combining the two types of surround inhibition with two different ways. The two models were evaluated with synthetic images and a set of challenging natural images, and the results show that both of the integrated models outperform the typical models with orientation-selective or non selective inhibition alone. The findings of this study suggest that V1 neurons with different types of center-surround interaction work in cooperative and adaptive ways at least when extracting organized structures from cluttered natural scenes. This work is expected to inspire efficient phenomenological models for engineering applications in field of computational machine-vision. PMID- 26136665 TI - Artificial gravity as a countermeasure for mitigating physiological deconditioning during long-duration space missions. AB - In spite of the experience gained in human space flight since Yuri Gagarin's historical flight in 1961, there has yet to be identified a completely effective countermeasure for mitigating the effects of weightlessness on humans. Were astronauts to embark upon a journey to Mars today, the 6-month exposure to weightlessness en route would leave them considerably debilitated, even with the implementation of the suite of piece-meal countermeasures currently employed. Continuous or intermittent exposure to simulated gravitational states on board the spacecraft while traveling to and from Mars, also known as artificial gravity, has the potential for enhancing adaptation to Mars gravity and re adaptation to Earth gravity. Many physiological functions are adversely affected by the weightless environment of spaceflight because they are calibrated for normal, Earth's gravity. Hence, the concept of artificial gravity is to provide a broad-spectrum replacement for the gravitational forces that naturally occur on the Earth's surface, thereby avoiding the physiological deconditioning that takes place in weightlessness. Because researchers have long been concerned by the adverse sensorimotor effects that occur in weightlessness as well as in rotating environments, additional study of the complex interactions among sensorimotor and other physiological systems in rotating environments must be undertaken both on Earth and in space before artificial gravity can be implemented. PMID- 26136666 TI - Dynamic optimization and conformity in health behavior and life enjoyment over the life cycle. AB - This article examines individual and social influences on investments in health and enjoyment from immediate consumption. Our lab experiment mimics the problem of health investment over a lifetime (Grossman, 1972a,b). Incentives to find the appropriate expenditures on life enjoyment and health are given by making in each period come period a function of previous health investments. In order to model social effects in the experiment, we randomly assigned individuals to chat/observation groups. Groups were permitted to freely chat between repeated lifetimes. Two treatments were employed: In the Independent-rewards treatment, an individual's rewards from investments in life enjoyment depend only on his choice and in the Interdependent-rewards treatment; rewards not only depend on an individual's choices but also on their similarity to the choices of the others in their group, generating a premium on conformity. The principal hypothesis is that gains from conformity increase variance in health behavior among groups and can lead to suboptimal performance. We tested three predictions and each was supported by the data: the Interdependent-rewards treatment (1) decreased within group variance, (2) increased between-group variance, and (3) increased the likelihood of behavior far from the optimum with respect to the dynamic problem. We also test and find support for a series of subsidiary hypotheses. We found: (4) Subjects engaged in helpful chat in both treatments; (5) there was significant heterogeneity among both subjects and groups in chat frequencies; and (6) chat was most common early in the experiment, and (7) the interdependent rewards treatment increased strategic chat frequency. Incentives for conformity appear to promote prosocial behavior, but also increase variance among groups, leading to convergence on suboptimal strategies for some groups. We discuss these results in light of the growing literature focusing on social networks and health outcomes. PMID- 26136667 TI - Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice. AB - Calcium (Ca(2+)) influx through voltage-gated Ca(2+) channels (VGCCs) induces numerous intracellular events such as neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation. It has been shown that genes related to Ca(2+) signaling, such as the CACNA1C, CACNB2, and CACNA1I genes that encode VGCC subunits, are associated with schizophrenia and other psychiatric disorders. Recently, VGCC beta-anchoring and -regulatory protein (BARP) was identified as a novel regulator of VGCC activity via the interaction of VGCC beta subunits. To examine the role of the BARP in higher brain functions, we generated BARP knockout (KO) mice and conducted a comprehensive battery of behavioral tests. BARP KO mice exhibited greatly reduced locomotor activity, as evidenced by decreased vertical activity, stereotypic counts in the open field test, and activity level in the home cage, and longer latency to complete a session in spontaneous T-maze alteration test, which reached "study-wide significance." Acoustic startle response was also reduced in the mutants. Interestingly, they showed multiple behavioral phenotypes that are seemingly opposite to those seen in the mouse models of schizophrenia and its related disorders, including increased working memory, flexibility, prepulse inhibition, and social interaction, and decreased locomotor activity, though many of these phenotypes are statistically weak and require further replications. These results demonstrate that BARP is involved in the regulation of locomotor activity and, possibly, emotionality. The possibility was also suggested that BARP KO mice may serve as a unique tool for investigating the pathogenesis/pathophysiology of schizophrenia and related disorders. Further evaluation of the molecular and physiological phenotypes of the mutant mice would provide new insights into the role of BARP in higher brain functions. PMID- 26136668 TI - Optimal hemodynamic response model for functional near-infrared spectroscopy. AB - Functional near-infrared spectroscopy (fNIRS) is an emerging non-invasive brain imaging technique and measures brain activities by means of near-infrared light of 650-950 nm wavelengths. The cortical hemodynamic response (HR) differs in attributes at different brain regions and on repetition of trials, even if the experimental paradigm is kept exactly the same. Therefore, an HR model that can estimate such variations in the response is the objective of this research. The canonical hemodynamic response function (cHRF) is modeled by two Gamma functions with six unknown parameters (four of them to model the shape and other two to scale and baseline respectively). The HRF model is supposed to be a linear combination of HRF, baseline, and physiological noises (amplitudes and frequencies of physiological noises are supposed to be unknown). An objective function is developed as a square of the residuals with constraints on 12 free parameters. The formulated problem is solved by using an iterative optimization algorithm to estimate the unknown parameters in the model. Inter-subject variations in HRF and physiological noises have been estimated for better cortical functional maps. The accuracy of the algorithm has been verified using 10 real and 15 simulated data sets. Ten healthy subjects participated in the experiment and their HRF for finger-tapping tasks have been estimated and analyzed. The statistical significance of the estimated activity strength parameters has been verified by employing statistical analysis (i.e., t-value > t critical and p-value < 0.05). PMID- 26136669 TI - Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training. AB - Gene transcription and translation in the hippocampus is of critical importance in hippocampus-dependent memory formation, including during Morris water maze (MWM) learning. Previous work using gene deletion models has shown that the immediate-early genes (IEGs) c-Fos, Egr-1, and Arc are crucial for such learning. Recently, we reported that induction of IEGs in sparse dentate gyrus neurons requires ERK MAPK signaling and downstream formation of a distinct epigenetic histone mark (i.e., phospho-acetylated histone H3). Until now, this signaling, epigenetic and gene transcriptional pathway has not been comprehensively studied in the MWM model. Therefore, we conducted a detailed study of the phosphorylation of ERK1/2 and serine10 in histone H3 (H3S10p) and induction of IEGs in the hippocampus of MWM trained rats and matched controls. MWM training evoked consecutive waves of ERK1/2 phosphorylation and H3S10 phosphorylation, as well as c-Fos, Egr-1, and Arc induction in sparse hippocampal neurons. The observed effects were most pronounced in the dentate gyrus. A positive correlation was found between the average latency to find the platform and the number of H3S10p positive dentate gyrus neurons. Furthermore, chromatin immuno-precipitation (ChIP) revealed a significantly increased association of phospho-acetylated histone H3 (H3K9ac-S10p) with the gene promoters of c-Fos and Egr-1, but not Arc, after MWM exposure compared with controls. Surprisingly, however, we found very little difference between IEG responses (regarding both protein and mRNA) in MWM trained rats compared with matched swim controls. We conclude that exposure to the water maze evokes ERK MAPK activation, distinct epigenetic changes and IEG induction predominantly in sparse dentate gyrus neurons. It appears, however, that a specific role for IEGs in the learning aspect of MWM training may become apparent in downstream AP-1- and Egr-1-regulated (second wave) genes and Arc dependent effector mechanisms. PMID- 26136670 TI - Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice. AB - L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs. In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i.p.) would produce alterations in behavioral tasks (open field or object recognition) in C57Bl/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57Bl/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus. We conclude that a single exposure to L KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57Bl/6j mice. PMID- 26136671 TI - Blocking of orexin receptors in the paraventricular nucleus of the thalamus has no effect on the expression of conditioned fear in rats. AB - The paraventricular nucleus of the thalamus (PVT) projects to the central nucleus of the amygdala and recent experimental evidence indicates a role for the PVT in conditioned fear. Furthermore, the PVT contains a high density of orexin receptors and fibers and acute injections of orexin antagonist into the PVT produce anxiolytic effects. The present study was done to determine if administration of a dual orexin receptor antagonist (DORA) in the region of the PVT interferes with the expression of conditioned fear in rats exposed to cued and contextual conditioning paradigms. Infusion of 0.5 MUl of the DORA N-biphenyl 2-yl-1-[(1-methyl-1H-benzimidazol-2yl) sulfanyl] acetyl-L-prolinamide at a concentration of 0.1, 1.0, and 10 nmol had no effect on the freezing produced by exposing rats to an auditory cue or the context associated with foot shock. In contrast, the 1.0 and 10 nmol doses were anxiolytic in the social interaction test. The results of the present study do not support a role for orexin receptors in the PVT in the expression of learned fear. The finding that the 1.0 and 10 nmol doses of DORA in the PVT region were anxiolytic in the social interaction test is consistent with other studies indicating a role for orexins in the PVT in anxiety-like behaviors. PMID- 26136672 TI - Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation. AB - Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols. PMID- 26136673 TI - Indeterminacy tolerance as a basis of hemispheric asymmetry within prefrontal cortex. AB - There is an important hemispheric distinction in the functional organization of prefrontal cortex (PFC) that has not been fully recognized and explored. Research with split-brain patients provides considerable evidence for a left hemisphere (LH) "interpreter" that abhors indeterminacy and automatically draws inferences to complete patterns (real or imaginary). It is suggested that this "interpreter" function may be a byproduct of the linguistic capabilities of the LH. This same literature initially limited the role of the right hemisphere (RH) to little more than visual organization. Recent reviews have garnered evidence for several different roles for the right PFC in reasoning, problem solving, and decision making. We here focus on the beneficial but neglected role of indeterminacy in real-world problem solving and argue that the right PFC complements the left PFC "interpreter" by maintaining, and even enhancing indeterminacy. Successful real world functioning is a delicate balancing act between these two systems. PMID- 26136675 TI - Corrigendum: Age-related slowing of response selection and production in a visual choice reaction time task. AB - [This corrects the article on p. 193 in vol. 9, PMID: 25954175.]. PMID- 26136674 TI - Impaired rapid error monitoring but intact error signaling following rostral anterior cingulate cortex lesions in humans. AB - Detecting one's own errors and appropriately correcting behavior are crucial for efficient goal-directed performance. A correlate of rapid evaluation of behavioral outcomes is the error-related negativity (Ne/ERN) which emerges at the time of the erroneous response over frontal brain areas. However, whether the error monitoring system's ability to distinguish between errors and correct responses at this early time point is a necessary precondition for the subsequent emergence of error awareness remains unclear. The present study investigated this question using error-related brain activity and vocal error signaling responses in seven human patients with lesions in the rostral anterior cingulate cortex (rACC) and adjoining ventromedial prefrontal cortex, while they performed a flanker task. The difference between errors and correct responses was severely attenuated in these patients indicating impaired rapid error monitong, but they showed no impairment in error signaling. However, impaired rapid error monitoring coincided with a failure to increase response accuracy on trials following errors. These results demonstrate that the error monitoring system's ability to distinguish between errors and correct responses at the time of the response is crucial for adaptive post-error adjustments, but not a necessary precondition for error awareness. PMID- 26136676 TI - A general framework for dynamic cortical function: the function-through-biased oscillations (FBO) hypothesis. AB - A central goal of neuroscience is to determine how the brain's relatively static anatomy can support dynamic cortical function, i.e., cortical function that varies according to task demands. In pursuit of this goal, scientists have produced a large number of experimental results and established influential conceptual frameworks, in particular communication-through-coherence (CTC) and gating-by-inhibition (GBI), but these data and frameworks have not provided a parsimonious view of the principles that underlie cortical function. Here I synthesize these existing experimental results and the CTC and GBI frameworks, and propose the function-through-biased-oscillations (FBO) hypothesis as a model to understand dynamic cortical function. The FBO hypothesis suggests that oscillatory voltage amplitude is the principal measurement that directly reflects cortical excitability, that asymmetries in voltage amplitude explain a range of brain signal phenomena, and that predictive variations in such asymmetric oscillations provide a simple and general model for information routing that can help to explain dynamic cortical function. PMID- 26136677 TI - Aberrant corticostriatal functional circuits in adolescents with Internet addiction disorder. AB - Abnormal structure and function in the striatum and prefrontal cortex (PFC) have been revealed in Internet addiction disorder (IAD). However, little is known about alterations of corticostriatal functional circuits in IAD. The aim of this study was to investigate the integrity of corticostriatal functional circuits and their relations to neuropsychological measures in IAD by resting-state functional connectivity (FC). Fourteen IAD adolescents and 15 healthy controls underwent resting-state fMRI scans. Using six predefined bilateral striatal regions-of interest, voxel-wise correlation maps were computed and compared between groups. Relationships between alterations of corticostriatal connectivity and clinical measurements were examined in the IAD group. Compared to controls, IAD subjects exhibited reduced connectivity between the inferior ventral striatum and bilateral caudate head, subgenual anterior cingulate cortex (ACC), and posterior cingulate cortex, and between the superior ventral striatum and bilateral dorsal/rostral ACC, ventral anterior thalamus, and putamen/pallidum/insula/inferior frontal gyrus (IFG), and between the dorsal caudate and dorsal/rostral ACC, thalamus, and IFG, and between the left ventral rostral putamen and right IFG. IAD subjects also showed increased connectivity between the left dorsal caudal putamen and bilateral caudal cigulate motor area. Moreover, altered cotricostriatal functional circuits were significantly correlated with neuropsychological measures. This study directly provides evidence that IAD is associated with alterations of corticostriatal functional circuits involved in the affective and motivation processing, and cognitive control. These findings emphasize that functional connections in the corticostriatal circuits are modulated by affective/motivational/cognitive states and further suggest that IAD may have abnormalities of such modulation in this network. PMID- 26136678 TI - Computational modeling suggests distinct, location-specific function of norepinephrine in olfactory bulb and piriform cortex. AB - Noradrenergic modulation from the locus coerulus is often associated with the regulation of sensory signal-to-noise ratio. In the olfactory system, noradrenergic modulation affects both bulbar and cortical processing, and has been shown to modulate the detection of low concentration stimuli. We here implemented a computational model of the olfactory bulb and piriform cortex, based on known experimental results, to explore how noradrenergic modulation in the olfactory bulb and piriform cortex interact to regulate odor processing. We show that as predicted by behavioral experiments in our lab, norepinephrine can play a critical role in modulating the detection and associative learning of very low odor concentrations. Our simulations show that bulbar norepinephrine serves to pre-process odor representations to facilitate cortical learning, but not recall. We observe the typical non-uniform dose-response functions described for norepinephrine modulation and show that these are imposed mainly by bulbar, but not cortical processing. PMID- 26136679 TI - A network model of basal ganglia for understanding the roles of dopamine and serotonin in reward-punishment-risk based decision making. AB - There is significant evidence that in addition to reward-punishment based decision making, the Basal Ganglia (BG) contributes to risk-based decision making (Balasubramani et al., 2014). Despite this evidence, little is known about the computational principles and neural correlates of risk computation in this subcortical system. We have previously proposed a reinforcement learning (RL) based model of the BG that simulates the interactions between dopamine (DA) and serotonin (5HT) in a diverse set of experimental studies including reward, punishment and risk based decision making (Balasubramani et al., 2014). Starting with the classical idea that the activity of mesencephalic DA represents reward prediction error, the model posits that serotoninergic activity in the striatum controls risk-prediction error. Our prior model of the BG was an abstract model that did not incorporate anatomical and cellular-level data. In this work, we expand the earlier model into a detailed network model of the BG and demonstrate the joint contributions of DA-5HT in risk and reward-punishment sensitivity. At the core of the proposed network model is the following insight regarding cellular correlates of value and risk computation. Just as DA D1 receptor (D1R) expressing medium spiny neurons (MSNs) of the striatum were thought to be the neural substrates for value computation, we propose that DA D1R and D2R co expressing MSNs are capable of computing risk. Though the existence of MSNs that co-express D1R and D2R are reported by various experimental studies, prior existing computational models did not include them. Ours is the first model that accounts for the computational possibilities of these co-expressing D1R-D2R MSNs, and describes how DA and 5HT mediate activity in these classes of neurons (D1R-, D2R-, D1R-D2R- MSNs). Starting from the assumption that 5HT modulates all MSNs, our study predicts significant modulatory effects of 5HT on D2R and co-expressing D1R-D2R MSNs which in turn explains the multifarious functions of 5HT in the BG. The experiments simulated in the present study relates 5HT to risk sensitivity and reward-punishment learning. Furthermore, our model is shown to capture reward punishment and risk based decision making impairment in Parkinson's Disease (PD). The model predicts that optimizing 5HT levels along with DA medications might be essential for improving the patients' reward-punishment learning deficits. PMID- 26136680 TI - Going beyond the current neuroinformatics infrastructure. PMID- 26136683 TI - Editorial: The molecular pathology of cognitive decline: focus on metals. PMID- 26136682 TI - Impaired Abeta clearance: a potential link between atherosclerosis and Alzheimer's disease. AB - Alzheimer's Disease (AD) and atherosclerosis remain two of the largest public health burdens in the world today. Although traditionally considered distinct pathological entities, mounting epidemiologic, clinical and experimental evidence suggests that cerebrovascular atherosclerosis and AD interact reciprocally to disrupt brain structure and function. Whereas the hypoperfusion and hypoxia caused by atherosclerosis of cerebral vessels may enhance the production of amyloid-beta peptide (Abeta), a peptide central to AD pathology, Abeta, in turn, may promote formation of atherosclerotic lesions through vascular oxidative stress and endothelial dysfunction leading to additional vascular damage. Here, we briefly review evidence suggesting that impaired clearance of Abeta is an additional, simultaneously occurring mechanism by which AD and cerebrovascular disease may be causally linked. We examine the literature supporting mechanisms by which flow-limiting large-artery stenosis, arterial stiffening and microvascular dysfunction could contribute to AD pathophysiology by impairing Abeta clearance and elevating brain levels of Abeta. Finally, we highlight the need for further research to improve our understanding of the complex interactions of AD and atherosclerosis with Abeta clearance, which may ultimately serve to guide the development of novel diagnostic and therapeutic approaches for this devastating and highly prevalent condition. PMID- 26136681 TI - Can insulin signaling pathways be targeted to transport Abeta out of the brain? AB - Although the causal role of Amyloid-beta (Abeta) in Alzheimer's disease (AD) is unclear, it is still reasonable to expect that lowering concentrations of Abeta in the brain may decrease the risk of developing the neurocognitive symptoms of the disease. Brain capillary endothelial cells forming the blood-brain barrier (BBB) express transporters regulating the efflux of Abeta out of the cerebral tissue. Age-related BBB dysfunctions, that have been identified in AD patients, might impair Abeta clearance from the brain. Thus, targeting BBB outward transport systems has been suggested as a way to stimulate the clearance of Abeta from the brain. Recent data indicate that the increase in soluble brain Abeta and behavioral impairments in 3*Tg-AD mice generated by months of intake of a high fat diet can be acutely reversed by the administration of a single dose of insulin. A concomitant increase in plasma Abeta suggests that clearance from the brain through the BBB is a likely mechanism for this rapid effect of insulin. Here, we review how BBB insulin response pathways could be stimulated to decrease brain Abeta concentrations and improve cognitive performance, at least on the short term. PMID- 26136684 TI - Combined inhibition of MEK and Aurora A kinase in KRAS/PIK3CA double-mutant colorectal cancer models. AB - Aurora A kinase and MEK inhibitors induce different, and potentially complementary, effects on the cell cycle of malignant cells, suggesting a rational basis for utilizing these agents in combination. In this work, the combination of an Aurora A kinase and MEK inhibitor was evaluated in pre-clinical colorectal cancer models, with a focus on identifying a subpopulation in which it might be most effective. Increased synergistic activity of the drug combination was identified in colorectal cancer cell lines with concomitant KRAS and PIK3CA mutations. Anti-proliferative effects were observed upon treatment of these double-mutant cell lines with the drug combination, and tumor growth inhibition was observed in double-mutant human tumor xenografts, though effects were variable within this subset. Additional evaluation suggests that degree of G2/M delay and p53 mutation status affect apoptotic activity induced by combination therapy with an Aurora A kinase and MEK inhibitor in KRAS and PIK3CA mutant colorectal cancer. Overall, in vitro and in vivo testing was unable to identify a subset of colorectal cancer that was consistently responsive to the combination of a MEK and Aurora A kinase inhibitor. PMID- 26136685 TI - Different toxic effects of YTX in tumor K-562 and lymphoblastoid cell lines. AB - Yessotoxin (YTX) modulates cellular phosphodiesterases (PDEs). In this regard, opposite effects had been described in the tumor model K-562 cell line and fresh human lymphocytes in terms of cell viability, cyclic adenosine 3',5'-cyclic monophosphate (cAMP) production and protein expression after YTX treatment. Studies in depth of the pathways activated by YTX in K-562 cell line, have demonstrated the activation of two different cell death types, apoptosis, and autophagy after 24 and 48 h of treatment, respectively. Furthermore, the key role of type 4A PDE (PDE4A) in both pathways activated by YTX was demonstrated. Therefore, taking into account the differences between cellular lines and fresh cells, a study of cell death pathways activated by YTX in a non-tumor cell line with mitotic activity, was performed. The cellular model used was the lymphoblastoid cell line that represents a non-tumor model with normal apoptotic and mitotic machinery. In this context, cell viability and cell proliferation, expression of proteins involved in cell death activated by YTX and mitochondrial mass, were studied after the incubation with the toxin. Opposite to the tumor model, no cell death activation was observed in lymphoblastoid cell line in the presence of YTX. In this sense, variations in apoptosis hallmarks were not detected in the lymphoblastoid cell line after YTX incubation, whereas this type I of programmed cell death was observed in K-562 cells. On the other hand, autophagy cell death was triggered in this cellular line, while other autophagic process is suggested in lymphoblastoid cells. These YTX effects are related to PDE4A in both cellular lines. In addition, while cell death is triggered in K-562 cells after YTX treatment, in lymphoblastoid cells the toxin stops cellular proliferation. These results point to YTX as a specific toxic compound of tumor cells, since in the non-tumor lymphoblastoid cell line, no cell death hallmarks are observed. PMID- 26136686 TI - High mobility group box 1 contributes to wound healing induced by inhibition of dipeptidylpeptidase 4 in cultured keratinocytes. AB - Dipeptidyl peptidase 4 (DPP4) is expressed in various tissues, including the skin, and DPP4 inhibitors, that are currently used for the treatment of diabetes, may be effective also for complications of diabetes that affect the skin. To assess the role of DPP4 in keratinocytes, after creating a scratch wound in a monolayer of NTCC 2544 cells, we evaluated DPP4 expression and monitored wound repair over time, after treatment with the DPP4 inhibitor 1(((1 (hydroxymethyl)cyclopentyl)amino)acetyl)2,5-cis-pyrrolidinedicarbonitrile (DPP4 In). Expression of DPP4 increased early and was maintained up to 48 h following the scratch as shown by western blot and immunostaining. Treatment with 10 MUM DPP4-In reduced DPP4 expression and significantly accelerated wound repair. This effect did not involve enhanced cell proliferation as shown by MTT proliferation assay, the lack of changes of cell cycle profiles and the slight inhibition of ERK phosphorylation. Enhancement of wound repair by DPP4 inhibition was prevented by the non-specific MMPs inhibitor GM6100 (5 MUM). Treatment with DPP4-In increased the expression of high mobility group box 1 (HMGB1), a substrate of this enzyme, and exposure of NCTC 2544 cells to DPP4-In and exogenous HMGB1 (10 nM) produced a non-additive effect. Finally the healing promoting effect of DPP4 In was prevented by pretreatment with a neutralizing anti-HMGB1 antibody. The present results suggest that DPP4 inhibition contributes to enhanced wound healing by inducing keratinocytes to migrate into a scratched area. This effect seems to be independent of cell proliferation and involves enhanced production of HMGB1. PMID- 26136687 TI - Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure. AB - Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID- 26136688 TI - Cloning, expression analysis, and RNA interference study of a HORMA domain containing autophagy-related gene 13 (ATG13) from the coleopteran beetle, Tenebrio molitor. AB - Autophagy is a process that is necessary during starvation, as it replenishes metabolic precursors by eliminating damaged organelles. Autophagy is mediated by more than 35 autophagy-related (Atg) proteins that participate in the nucleation, elongation, and curving of the autophagosome membrane. In a pursuit to address the role of autophagy during development and immune resistance of the mealworm beetle, Tenebrio molitor, we screened ATG gene sequences from the whole-larva transcriptome database. We identified a homolog of ATG13 gene in T. molitor (designated as TmATG13) that comprises a cDNA of 1176 bp open reading frame (ORF) encoding a protein of 391 amino acids. Analyses of the structure-specific features of TmAtg13 showed an intrinsically disordered middle and C-terminal region that was rich in regulatory phosphorylation sites. The N-terminal Atg13 domain had a HORMA (Hop1, Rev7, and Mad2) fold containing amino acid residues conserved across the Atg13 insect orthologs. A quantitative reverse-transcription polymerase chain reaction analysis revealed that TmATG13 was expressed ubiquitously during all developmental stages of the insect. TmATG13 mRNA expression was high in the fat body and gut of the larval and adult stages of the insect. The TmATG13 transcripts were expressed at a high level until 6 days of ovarian development, followed by a significant decline. Silencing of ATG13 transcripts in T. molitor larvae showed a reduced survivability of 39 and 38% in response to Escherichia coli and Staphylococcus aureus infection. Furthermore, the role of TmAtg13 in initiating autophagy as a part of the host cell autophagic complex of the host cells against the intracellular pathogen Listeria monocytogenes is currently under study and will be critical to unfold the structure-function relationships. PMID- 26136689 TI - The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signaling, and their interplay. AB - Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1) redox signaling and (2) macromolecule damage. Mechanistic knowledge of how exercise-induced redox signaling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signaling and DNA damage, using hydroxyl radical ((.)OH) and hydrogen peroxide (H2O2) as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signaling and damage. Indeed, H2O2 can participate in two electron signaling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and (.)OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signaling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signaling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation. PMID- 26136690 TI - Resting state MEG oscillations show long-range temporal correlations of phase synchrony that break down during finger movement. AB - The capacity of the human brain to interpret and respond to multiple temporal scales in its surroundings suggests that its internal interactions must also be able to operate over a broad temporal range. In this paper, we utilize a recently introduced method for characterizing the rate of change of the phase difference between MEG signals and use it to study the temporal structure of the phase interactions between MEG recordings from the left and right motor cortices during rest and during a finger-tapping task. We use the Hilbert transform to estimate moment-to-moment fluctuations of the phase difference between signals. After confirming the presence of scale-invariance we estimate the Hurst exponent using detrended fluctuation analysis (DFA). An exponent of >0.5 is indicative of long range temporal correlations (LRTCs) in the signal. We find that LRTCs are present in the alpha/MU and beta frequency bands of resting state MEG data. We demonstrate that finger movement disrupts LRTCs correlations, producing a phase relationship with a structure similar to that of Gaussian white noise. The results are validated by applying the same analysis to data with Gaussian white noise phase difference, recordings from an empty scanner and phase-shuffled time series. We interpret the findings through comparison of the results with those we obtained from an earlier study during which we adopted this method to characterize phase relationships within a Kuramoto model of oscillators in its sub-critical, critical, and super-critical synchronization states. We find that the resting state MEG from left and right motor cortices shows moment-to-moment fluctuations of phase difference with a similar temporal structure to that of a system of Kuramoto oscillators just prior to its critical level of coupling, and that finger tapping moves the system away from this pre-critical state toward a more random state. PMID- 26136691 TI - Serum from human burn victims impairs myogenesis and protein synthesis in primary myoblasts. AB - The pathophysiological response to a severe burn injury involves a robust increase in circulating inflammatory/endocrine factors and a hypermetabolic state, both of which contribute to prolonged skeletal muscle atrophy. In order to characterize the role of circulating factors in muscle atrophy following a burn injury, human skeletal muscle satellite cells were grown in culture and differentiated to myoblasts/myotubes in media containing serum from burn patients or healthy, age, and sex-matched controls. While incubation in burn serum did not affect NFkappaB signaling, cells incubated in burn serum displayed a transient increase in STAT3 phosphorlyation (Tyr705) after 48 h of treatment with burn serum (~ + 70%; P < 0.01), with these levels returning to normal by 96 h. Muscle cells differentiated in burn serum displayed reduced myogenic fusion signaling (phospho-STAT6 (Tyr641), ~-75%; ADAM12, ~-20%; both P < 0.01), and reduced levels of myogenin (~-75%; P < 0.05). Concomitantly, myotubes differentiated in burn serum demonstrated impaired myogenesis (assessed by number of nuclei/myotube). Incubation in burn serum for 96 h did not increase proteolytic signaling (assessed via caspase-3 and ubiquitin levels), but reduced anabolic signaling [p p70S6k (Ser421/Thr424), -30%; p-rpS6 (Ser240/244), ~-50%] and impaired protein synthesis (-24%) (P < 0.05). This resulted in a loss of total protein content ( 18%) and reduced cell size (-33%) (P < 0.05). Overall, incubation of human muscle cells in serum from burn patients results in impaired myogenesis and reduced myotube size, indicating that circulating factors may play a significant role in muscle loss and impaired muscle recovery following burn injury. PMID- 26136692 TI - Modern Brain Mapping - What Do We Map Nowadays? PMID- 26136693 TI - Measuring individuals' response quality in self-administered psychological tests: an introduction to Gendre's functional method. AB - The functional method is a new test theory using a new scoring method that assumes complexity in test structure, and thus takes into account every correlation between factors and items. The main specificity of the functional method is to model test scores by multiple regression instead of estimating them by using simplistic sums of points. In order to proceed, the functional method requires the creation of hyperspherical measurement space, in which item responses are expressed by their correlation with orthogonal factors. This method has three main qualities. First, measures are expressed in the absolute metric of correlations; therefore, items, scales and persons are expressed in the same measurement space using the same single metric. Second, factors are systematically orthogonal and without errors, which is optimal in order to predict other outcomes. Such predictions can be performed to estimate how one would answer to other tests, or even to model one's response strategy if it was perfectly coherent. Third, the functional method provides measures of individuals' response validity (i.e., control indices). Herein, we propose a standard procedure in order to identify whether test results are interpretable and to exclude invalid results caused by various response biases based on control indices. PMID- 26136694 TI - Noncontextuality with marginal selectivity in reconstructing mental architectures. AB - We present a general theory of series-parallel mental architectures with selectively influenced stochastically non-independent components. A mental architecture is a hypothetical network of processes aimed at performing a task, of which we only observe the overall time it takes under variable parameters of the task. It is usually assumed that the network contains several processes selectively influenced by different experimental factors, and then the question is asked as to how these processes are arranged within the network, e.g., whether they are concurrent or sequential. One way of doing this is to consider the distribution functions for the overall processing time and compute certain linear combinations thereof (interaction contrasts). The theory of selective influences in psychology can be viewed as a special application of the interdisciplinary theory of (non)contextuality having its origins and main applications in quantum theory. In particular, lack of contextuality is equivalent to the existence of a "hidden" random entity of which all the random variables in play are functions. Consequently, for any given value of this common random entity, the processing times and their compositions (minima, maxima, or sums) become deterministic quantities. These quantities, in turn, can be treated as random variables with (shifted) Heaviside distribution functions, for which one can easily compute various linear combinations across different treatments, including interaction contrasts. This mathematical fact leads to a simple method, more general than the previously used ones, to investigate and characterize the interaction contrast for different types of series-parallel architectures. PMID- 26136695 TI - The Resilience Program: preliminary evaluation of a mentalization-based education program. AB - In order to manage with the burden of mental health problems in the world we need to develop cost-effective and safe preventive interventions. Education about resilience to support the ability to cope with life challenges in general, may be a useful strategy. We consider the concepts of Theory of Mind and Mentalization to be relevant in this context. In this paper we describe a simple modular intervention program based on these concepts which can be tailored to specific needs and situations in individual therapy as well as group levels. The program has shown promising results in pilot studies and is now tested in controlled trials in settings such as schools and educational institutions, adults diagnosed with ADHD, and children in care. PMID- 26136696 TI - Appraising the role of visual threat in speeded detection and classification tasks. AB - This research examines the speeded detection and, separately, classification of photographic images of animals. In the initial experiments each display contained various images of animals and, in the detection task, participants responded whether a display contained only images of birds or also included an oddball target image of a cat or dog. In the classification search task, a target was always present and participants classified this as an image of a cat or a dog. Half of the target images depicted the animal in a non-threatening state and the remaining half images depicted the animal in a threatening state. A complex pattern of effects emerged showing some evidence of more efficient detection of a threatening than non-threatening target. No corresponding pattern emerged in the data for the classification task. Next the tasks were repeated when the stimuli were more carefully matched in terms of general pose and salience of facial features. Now the effects in the detection task were reduced but more consistent than before. Threatening targets were more readily detected than non-threatening targets. In addition, non-threatening targets were more readily classified than threatening targets. The nature of these effects appears to reflect decisional/response mechanisms and not search processes. The performance benefit for the non-threatening images was replicated in a final classification task in which, on each trial, only a single peripheral image was presented. The results demonstrate that a number of different affective and perceptual factors can influence performance in speeded search tasks and these may well be confounded with the variation in threat content of the experimental stimuli. The evidence for the automatic detection of visual threat remains illusive. PMID- 26136697 TI - Age, gender, and puberty influence the development of facial emotion recognition. AB - Our ability to differentiate between simple facial expressions of emotion develops between infancy and early adulthood, yet few studies have explored the developmental trajectory of emotion recognition using a single methodology across a wide age-range. We investigated the development of emotion recognition abilities through childhood and adolescence, testing the hypothesis that children's ability to recognize simple emotions is modulated by chronological age, pubertal stage and gender. In order to establish norms, we assessed 478 children aged 6-16 years, using the Ekman-Friesen Pictures of Facial Affect. We then modeled these cross-sectional data in terms of competence in accurate recognition of the six emotions studied, when the positive correlation between emotion recognition and IQ was controlled. Significant linear trends were seen in children's ability to recognize facial expressions of happiness, surprise, fear, and disgust; there was improvement with increasing age. In contrast, for sad and angry expressions there is little or no change in accuracy over the age range 6 16 years; near-adult levels of competence are established by middle-childhood. In a sampled subset, pubertal status influenced the ability to recognize facial expressions of disgust and anger; there was an increase in competence from mid to late puberty, which occurred independently of age. A small female advantage was found in the recognition of some facial expressions. The normative data provided in this study will aid clinicians and researchers in assessing the emotion recognition abilities of children and will facilitate the identification of abnormalities in a skill that is often impaired in neurodevelopmental disorders. If emotion recognition abilities are a good model with which to understand adolescent development, then these results could have implications for the education, mental health provision and legal treatment of teenagers. PMID- 26136698 TI - An interference account of the missing-VP effect. AB - Sentences with doubly center-embedded relative clauses in which a verb phrase (VP) is missing are sometimes perceived as grammatical, thus giving rise to an illusion of grammaticality. In this paper, we provide a new account of why missing-VP sentences, which are both complex and ungrammatical, lead to an illusion of grammaticality, the so-called missing-VP effect. We propose that the missing-VP effect in particular, and processing difficulties with multiply center embedded clauses more generally, are best understood as resulting from interference during cue-based retrieval. When processing a sentence with double center-embedding, a retrieval error due to interference can cause the verb of an embedded clause to be erroneously attached into a higher clause. This can lead to an illusion of grammaticality in the case of missing-VP sentences and to processing complexity in the case of complete sentences with double center embedding. Evidence for an interference account of the missing-VP effect comes from experiments that have investigated the missing-VP effect in German using a speeded grammaticality judgments procedure. We review this evidence and then present two new experiments that show that the missing-VP effect can be found in German also with less restricting procedures. One experiment was a questionnaire study which required grammaticality judgments from participants without imposing any time constraints. The second experiment used a self-paced reading procedure and did not require any judgments. Both experiments confirm the prior findings of missing-VP effects in German and also show that the missing-VP effect is subject to a primacy effect as known from the memory literature. Based on this evidence, we argue that an account of missing-VP effects in terms of interference during cue-based retrieval is superior to accounts in terms of limited memory resources or in terms of experience with embedded structures. PMID- 26136699 TI - The relationship of speech intelligibility with hearing sensitivity, cognition, and perceived hearing difficulties varies for different speech perception tests. AB - Listeners vary in their ability to understand speech in noisy environments. Hearing sensitivity, as measured by pure-tone audiometry, can only partly explain these results, and cognition has emerged as another key concept. Although cognition relates to speech perception, the exact nature of the relationship remains to be fully understood. This study investigates how different aspects of cognition, particularly working memory and attention, relate to speech intelligibility for various tests. Perceptual accuracy of speech perception represents just one aspect of functioning in a listening environment. Activity and participation limits imposed by hearing loss, in addition to the demands of a listening environment, are also important and may be better captured by self report questionnaires. Understanding how speech perception relates to self reported aspects of listening forms the second focus of the study. Forty-four listeners aged between 50 and 74 years with mild sensorineural hearing loss were tested on speech perception tests differing in complexity from low (phoneme discrimination in quiet), to medium (digit triplet perception in speech-shaped noise) to high (sentence perception in modulated noise); cognitive tests of attention, memory, and non-verbal intelligence quotient; and self-report questionnaires of general health-related and hearing-specific quality of life. Hearing sensitivity and cognition related to intelligibility differently depending on the speech test: neither was important for phoneme discrimination, hearing sensitivity alone was important for digit triplet perception, and hearing and cognition together played a role in sentence perception. Self-reported aspects of auditory functioning were correlated with speech intelligibility to different degrees, with digit triplets in noise showing the richest pattern. The results suggest that intelligibility tests can vary in their auditory and cognitive demands and their sensitivity to the challenges that auditory environments pose on functioning. PMID- 26136700 TI - Why I teach the controversy: using creationism to teach critical thinking. AB - Creationism and intelligent design are terms used to describe supernatural explanations for the origin of life, and the diversity of species on this planet. Many scientists have argued that the science classroom is no place for discussion of creationism. When I began teaching I did not teach creationism, as I focused instead on my areas of expertise. Over time it became clear that students had questions about creationism, and did not understand the difference between a scientific approach to knowledge and non-scientific approaches. This led me to wonder whether ignoring supernatural views allowed them to remain as viable "alternatives" to scientific hypotheses, in the minds of students. Also, a psychology class is an ideal place to discuss not only the scientific method but also the cognitive errors associated with non-science views. I began to explain creationism in my classes, and to model the scientific thought process that leads to a rejection of creationism. My approach is consistent with research that demonstrates that teaching content alone is insufficient for students to develop critical thinking and my admittedly anecdotal experience leads me to conclude that "teaching the controversy" has benefits for science students. PMID- 26136702 TI - Atypical object exploration in infants at-risk for autism during the first year of lifer. AB - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder usually diagnosed by the end of the second year of life. Early signs of ASD within the first year of life are still unclear. The main purpose of the present study was to compare object exploration skills between infants at-risk for ASD and typically developing (TD) infants to determine early markers for autism within the first year of life. Sixteen at-risk infants and 16 TD infants were longitudinally followed from 6 to 15 months of age during an object exploration task involving three objects with distinct size, shape, and texture, i.e., a long rattle, a rigid circular ball, and a soft circular koosh ball. All sessions were videotaped for coding of manual exploration (grasping and dropping), oral exploration (mouthing), and visual exploration (looking). We also obtained follow-up outcomes using various developmental questionnaires at 18 months and email follow-up on developmental delays/ASD diagnosis after the infants' second birthdays. Our results showed object-based differences in exploration patterns that extended across both groups. We also noticed context-dependent group differences for various exploratory behaviors across objects and ages. Specifically, at 6 months, at-risk infants showed less grasping of the rigid ball as well as less mouthing and greater looking at the rattle compared to TD infants. At 9 and 12 months, at risk infants demonstrated significantly lower levels of purposeful dropping of all objects and greater looking at the rattle. Lastly, at 15 months, at-risk infants showed persistent mouthing of the rigid ball and rattle compared to TD infants. In addition, 10 out of 16 at-risk infants developed various motor, social, and language delays or ASD diagnosis at follow-up. Taken together, early context-dependent delays/abnormalities in object exploration could be markers for future developmental delays in infants at-risk for autism. Moreover, promoting early object experiences through socially embedded, free and structured play could have significant implications for multisystem development including perceptuo-motor, social communication, and cognitive development in at-risk infants. PMID- 26136703 TI - Augmented feedback influences upper limb reaching movement times but does not explain violations of Fitts' Law. AB - Fitts' (1954) classic theorem asserts that the movement time (MT) of voluntary reaches is determined by amplitude and width requirements (i.e., index of difficulty: ID). Actions associated with equivalent IDs should elicit equivalent MTs regardless of the amplitude and/ or width requirements. However, contemporary research has reported that amplitude-based contributions to IDs yield larger increases in MTs than width-based contributions. This discrepancy may relate to the presence of augmented terminal feedback in Fitts' original research, which has not been provided in more recent investigations (e.g., Heath et al., 2011). To address this issue, participants performed reaching movements during two sessions wherein feedback regarding terminal accuracy was either provided or withheld. It was hypothesized that the absence of augmented terminal feedback would result in a stereotyped performance across target widths and explain the violation of Fitts' theorem. Yet, the results revealed distinct influences of amplitude- and width-based manipulations on MT, which also persisted across feedback conditions. This finding supports the assertion that the unitary nature of Fitts' theorem does not account for a continuous range of movement amplitudes and target widths. A secondary analysis was competed in an attempt to further investigate the violation of Fitts' Law. Based on error rates, participants were segregated into accuracy- and speed-prone groups. Additionally, target's IDs were recalculated based on each participant's performance using the effective target width (i.e., IDWe) instead of the nominal target width. When using MT data from the accuracy-prone group with this IDWe, the aforementioned violation was alleviated. Overall, augmented terminal feedback did not explain the violation of Fitts' theorem, although one should consider using the effective target width and participant's strategy in future investigations. PMID- 26136704 TI - Answering questions about consciousness by modeling perception as covert behavior. AB - Two main open questions in current consciousness research concern (i) the neural correlates of consciousness (NCC) and (ii) the relationship between neural activity and first-person, subjective experience. Here, possible answers are sketched for both of these, by means of a model-based analysis of what is required for one to admit having a conscious experience. To this end, a model is proposed that allows reasoning, albeit necessarily in a simplistic manner, about all of the so called "easy problems" of consciousness, from discrimination of stimuli to control of behavior and language. First, it is argued that current neuroscientific knowledge supports the view of perception and action selection as two examples of the same basic phenomenon, such that one can meaningfully refer to neuronal activations involved in perception as covert behavior. Building on existing neuroscientific and psychological models, a narrative behavior model is proposed, outlining how the brain selects covert (and sometimes overt) behaviors to construct a complex, multi-level narrative about what it is like to be the individual in question. It is hypothesized that we tend to admit a conscious experience of X if, at the time of judging consciousness, we find ourselves acceptably capable of performing narrative behavior describing X. It is argued that the proposed account reconciles seemingly conflicting empirical results, previously presented as evidence for competing theories of consciousness, and suggests that well-defined, experiment-independent NCCs are unlikely to exist. Finally, an analysis is made of what the modeled narrative behavior machinery is and is not capable of. It is discussed how an organism endowed with such a machinery could, from its first-person perspective, come to adopt notions such as "subjective experience," and of there being "hard problems," and "explanatory gaps" to be addressed in order to understand consciousness. PMID- 26136701 TI - Possible functional links among brain- and skull-related genes selected in modern humans. AB - The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benitez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross modular concepts, properties most clearly manifested in language. PMID- 26136705 TI - Understanding the human dimensions of a sustainable energy transition. AB - Global climate change threatens the health, economic prospects, and basic food and water sources of people. A wide range of changes in household energy behavior is needed to realize a sustainable energy transition. We propose a general framework to understand and encourage sustainable energy behaviors, comprising four key issues. First, we need to identify which behaviors need to be changed. A sustainable energy transition involves changes in a wide range of energy behaviors, including the adoption of sustainable energy sources and energy efficient technology, investments in energy efficiency measures in buildings, and changes in direct and indirect energy use behavior. Second, we need to understand which factors underlie these different types of sustainable energy behaviors. We discuss three main factors that influence sustainable energy behaviors: knowledge, motivations, and contextual factors. Third, we need to test the effects of interventions aimed to promote sustainable energy behaviors. Interventions can be aimed at changing the actual costs and benefits of behavior, or at changing people's perceptions and evaluations of different costs and benefits of behavioral options. Fourth, it is important to understand which factors affect the acceptability of energy policies and energy systems changes. We discuss important findings from psychological studies on these four topics, and propose a research agenda to further explore these topics. We emphasize the need of an integrated approach in studying the human dimensions of a sustainable energy transition that increases our understanding of which general factors affect a wide range of energy behaviors as well as the acceptability of different energy policies and energy system changes. PMID- 26136706 TI - The relationship between two types of impaired emotion processing: repressive coping and alexithymia. AB - The constructs of repressive coping and alexithymia are both related to impaired emotion processing, yet individuals with a repressive coping style (repressors) score lower than controls on standard self-report measures of alexithymia. A large body of evidence indicates that repressors avoid negative affect. Therefore, the current study examined the relationship between repressive coping and alexithymia by using independently-rated interviews with the aim of bypassing repressors' tendency of avoiding negative affect. Results showed that repressors scored high on alexithymia, similar to anxious individuals on the independently rated interview, but scored low on alexithymia on a questionnaire measure. Our findings confirm a link between alexithymia and repressive coping and stress the need for non-standard measures in exploring the nature of the relationship between repressive coping and alexithymia. PMID- 26136707 TI - Cultural perspectives on children's tadpole drawings: at the interface between representation and production. AB - This study investigated tadpole self-drawings from 183 three- to six-year-old children living in seven cultural groups, representing three ecosocial contexts. Based on assumed general production principles, the influence of cultural norms and values upon specific characteristics of the tadpole drawings was examined. The results demonstrated that children from all cultural groups realized the body proportion effect in the self-drawings, indicating universal production principles. However, children differed in single drawing characteristics, depending on the specific ecosocial context. Children from Western and non Western urban educated contexts drew themselves rather tall, with many facial features, and preferred smiling facial expressions, while children from rural traditional contexts depicted themselves significantly smaller, with less facial details, and neutral facial expressions. PMID- 26136709 TI - Brain activity and cognition: a connection from thermodynamics and information theory. AB - The connection between brain and mind is an important scientific and philosophical question that we are still far from completely understanding. A crucial point to our work is noticing that thermodynamics provides a convenient framework to model brain activity, whereas cognition can be modeled in information-theoretical terms. In fact, several models have been proposed so far from both approaches. A second critical remark is the existence of deep theoretical connections between thermodynamics and information theory. In fact, some well-known authors claim that the laws of thermodynamics are nothing but principles in information theory. Unlike in physics or chemistry, a formalization of the relationship between information and energy is currently lacking in neuroscience. In this paper we propose a framework to connect physical brain and cognitive models by means of the theoretical connections between information theory and thermodynamics. Ultimately, this article aims at providing further insight on the formal relationship between cognition and neural activity. PMID- 26136708 TI - Musical hallucinations: review of treatment effects. AB - BACKGROUND: Despite an increased scientific interest in musical hallucinations over the past 25 years, treatment protocols are still lacking. This may well be due to the fact that musical hallucinations have multiple causes, and that published cases are relatively rare. OBJECTIVE: To review the effects of published treatment methods for musical hallucinations. METHODS: A literature search yielded 175 articles discussing a total number of 516 cases, of which 147 articles discussed treatment in 276 individuals. We analyzed the treatment results in relation to the etiological factor considered responsible for the mediation of the musical hallucinations, i.e., idiopathic/hypoacusis, psychiatric disorder, brain lesion, and other pathology, epilepsy or intoxication/pharmacology. RESULTS: Musical hallucinations can disappear without intervention. When hallucinations are bearable, patients can be reassured without any other treatment. However, in other patients musical hallucinations are so disturbing that treatment is indicated. Distinct etiological groups appear to respond differently to treatment. In the hypoacusis group, treating the hearing impairment can yield significant improvement and coping strategies (e.g., more acoustic stimulation) are frequently helpful. Pharmacological treatment methods can also be successful, with antidepressants being possibly more helpful than antiepileptics (which are still better than antipsychotics). The limited use of acetylcholinesterase inhibitors has looked promising. Musical hallucinations occurring as part of a psychiatric disorder tend to respond well to psychopharmacological treatments targeting the underlying disorder. Musical hallucinations experienced in the context of brain injuries and epilepsy tend to respond well to antiepileptics, but their natural course is often benign, irrespective of any pharmacological treatment. When intoxication/pharmacology is the main etiological factor, it is important to stop or switch the causative substance or medication. CONCLUSION: Treatments for musical hallucinations tend to yield favorable results when they target the main etiological factor of these phenomena. There is a need to establish the natural course of musical hallucinations, their response to non-pharmacological treatments, and their effects on the patient's quality of life. There is also a need to standardize the assessment of treatment responses, and document long-term follow up. PMID- 26136711 TI - Adjustment of speaker's referential expressions to an addressee's likely knowledge and link with theory of mind abilities. AB - To communicate cooperatively, speakers must determine what constitutes the common ground with their addressee and adapt their referential choices accordingly. Assessing another person's knowledge requires a social cognition ability termed theory of mind (ToM). This study relies on a novel referential communication task requiring probabilistic inferences of the knowledge already held by an addressee prior to the study. Forty participants were asked to present 10 movie characters and the addressee, who had the same characters in a random order, was asked to place them in order. ToM and other aspects of social cognition were also assessed. Participants used more information when presenting likely unknown than likely known movie characters. They particularly increased their use of physical descriptors, which most often accompanied movie-related information. Interestingly, a significant relationship emerged between our ToM test and the increased amount of information given for the likely unknown characters. These results suggest that speakers use ToM to infer their addressee's likely knowledge and accordingly adapt their referential expressions. PMID- 26136710 TI - Hypnosis-based psychodynamic treatment in ALS: a longitudinal study on patients and their caregivers. AB - BACKGROUND: Evidence of psychological treatment efficacy is strongly needed in ALS, particularly regarding long-term effects. METHODS: Fifteen patients participated in a hypnosis treatment and self-hypnosis training protocol after an in-depth psychological and neurological evaluation. Patients' primary caregivers and 15 one-by-one matched control patients were considered in the study. Measurements of anxiety, depression and quality of life (QoL) were collected at the baseline, post-treatment, and after 3 and 6 months from the intervention. Bayesian linear mixed-models were used to evaluate the impact of treatment and defense style on patients' anxiety, depression, QoL, and functional impairment (ALSFRS-r), as well as on caregivers' anxiety and depression. RESULTS: The statistical analyses revealed an improvement in psychological variables' scores immediately after the treatment. Amelioration in patients' and caregivers' anxiety as well as caregivers' depression, were found to persist at 3 and 6 months follow-ups. The observed massive use of primitive defense mechanisms was found to have a reliable and constant buffer effect on psychopathological symptoms in both patients and caregivers. Notably, treated patients decline in ALSFRS-r score was observed to be slower than that of control group's patients. DISCUSSION: Our brief psychodynamic hypnosis-based treatment showed efficacy both at psychological and physical levels in patients with ALS, and was indirectly associated to long-lasting benefits in caregivers. The implications of peculiar psychodynamic factors and mind-body techniques are discussed. Future directions should be oriented toward a convergence of our results and further psychological interventions, in order to delineate clinical best practices for ALS. PMID- 26136712 TI - Integrating attentional control theory and the strength model of self-control. AB - In the present article, we argue that it may be fruitful to incorporate the ideas of the strength model of self-control into the core assumptions of the well established attentional control theory (ACT). In ACT, it is assumed that anxiety automatically leads to attention disruption and increased distractibility, which may impair subsequent cognitive or perceptual-motor performance, but only if individuals do not have the ability to counteract this attention disruption. However, ACT does not clarify which process determines whether one can volitionally regulate attention despite experiencing high levels of anxiety. In terms of the strength model of self-control, attention regulation can be viewed as a self-control act depending on the momentary availability of self-control strength. We review literature that has revealed that self-control strength moderates the anxiety-performance relationship, discuss how to integrate these two theoretical models, and offer practical recommendations of how to counteract negative anxiety effects. PMID- 26136713 TI - Commentary: Merging of long-term memories in an insect. PMID- 26136714 TI - Categorical perception of lexical tones in mandarin-speaking congenital amusics. AB - Previous research suggests that within Mandarin-speaking congenital amusics, only a subgroup has behavioral lexical tone perception impairments (tone agnosia), whereas the rest of amusics do not. The purpose of the current study was to investigate the categorical nature of lexical tone perception in Mandarin speaking amusics with and without behavioral lexical tone deficits. Three groups of listeners (controls, pure amusics, and amusics with tone agnosia) participated in tone identification and discrimination tasks. Indexes of the categorical perception (CP) of a physical continuum of fundamental frequencies ranging from a rising to level tone were measured. Specifically, the stimulus durations were manipulated at 100 and 200 ms. For both stimulus durations, all groups exhibited similar categorical boundaries. The pure amusics showed sharp identification slopes and significantly peaked discrimination functions similar to those of normal controls. However, such essential characteristics for the CP of lexical tones were not observed in amusics with tone agnosia. An enlarged step-size from 20 to 35 Hz was not able to produce any discrimination peaks in tone agnosics either. The current study revealed that only amusics with tone agnosia showed a lack of categorical tone perception, while the pure amusics demonstrated typical CP of lexical tones, indicating that the deficit of pitch processing in music does not necessarily result in the deficit in the CP of lexical tones. The different performance between congenital amusics with and without tone agnosia provides a new perspective on the proposition of the relationship between music and speech perception. PMID- 26136715 TI - Mind wandering "Ahas" versus mindful reasoning: alternative routes to creative solutions. AB - Based on mixed results linking both mindfulness and its opposing construct mind wandering to enhanced creativity, we predicted that the relationship between mindfulness and creativity might depend on whether creative problems are approached through analytic strategy or through "insight" (i.e., sudden awareness of a solution). Study 1 investigated the relationship between trait mindfulness and compound remote associates problem solving as a function of participants' self-reported approach to each problem. The results revealed a negative relationship between mindfulness and problem-solving overall. However, more detailed analysis revealed that mindfulness was associated with impaired problem solving when approaching problems with insight, but increased problem solving when using analysis. In Study 2, we manipulated participants' problem-solving approach through instructions. We again found a negative relationship between mindfulness and creative performance in general, however, more mindful participants again performed better when instructed to approach problems analytically. PMID- 26136716 TI - Motivating the unmotivated: how can health behavior be changed in those unwilling to change? PMID- 26136717 TI - Online communication as a window to conspiracist worldviews. AB - In spite of the social stigma surrounding them, conspiracy theories are a common topic of public debate on the Internet. The content and tone of these discussions provide a useful insight into the structure of conspiracist belief systems and the psychological characteristics of those who believe and disbelieve in conspiracy theories. In this focused review, we relate patterns of behavior found in online comments to the broader research literature on the psychology of conspiracy theories. Most notably, as conspiracism has its basis in disbelieving a mainstream or received narrative rather than in believing a specific alternative, most conspiracist arguments tend to fall along those same lines. Finally, we examine the implications of this methodology for future research into online discussion, particularly among hard-to-research populations. PMID- 26136718 TI - Positional priming of visual pop-out search is supported by multiple spatial reference frames. AB - The present study investigates the representations(s) underlying positional priming of visual 'pop-out' search (Maljkovic and Nakayama, 1996). Three search items (one target and two distractors) were presented at different locations, in invariant (Experiment 1) or random (Experiment 2) cross-trial sequences. By these manipulations it was possible to disentangle retinotopic, spatiotopic, and object centered priming representations. Two forms of priming were tested: target location facilitation (i.e., faster reaction times - RTs- when the trial n target is presented at a trial n-1 target relative to n-1 blank location) and distractor location inhibition (i.e., slower RTs for n targets presented at n-1 distractor compared to n-1 blank locations). It was found that target locations were coded in positional short-term memory with reference to both spatiotopic and object centered representations (Experiment 1 vs. 2). In contrast, distractor locations were maintained in an object-centered reference frame (Experiments 1 and 2). We put forward the idea that the uncertainty induced by the experiment manipulation (predictable versus random cross-trial item displacements) modulates the transition from object- to space-based representations in cross-trial memory for target positions. PMID- 26136719 TI - Length and orientation constancy learning in 2-dimensions with auditory sensory substitution: the importance of self-initiated movement. AB - A subset of sensory substitution (SS) devices translate images into sounds in real time using a portable computer, camera, and headphones. Perceptual constancy is the key to understanding both functional and phenomenological aspects of perception with SS. In particular, constancies enable object externalization, which is critical to the performance of daily tasks such as obstacle avoidance and locating dropped objects. In order to improve daily task performance by the blind, and determine if constancies can be learned with SS, we trained blind (N = 4) and sighted (N = 10) individuals on length and orientation constancy tasks for 8 days at about 1 h per day with an auditory SS device. We found that blind and sighted performance at the constancy tasks significantly improved, and attained constancy performance that was above chance. Furthermore, dynamic interactions with stimuli were critical to constancy learning with the SS device. In particular, improved task learning significantly correlated with the number of spontaneous left-right head-tilting movements while learning length constancy. The improvement from previous head-tilting trials even transferred to a no-head tilt condition. Therefore, not only can SS learning be improved by encouraging head movement while learning, but head movement may also play an important role in learning constancies in the sighted. In addition, the learning of constancies by the blind and sighted with SS provides evidence that SS may be able to restore vision-like functionality to the blind in daily tasks. PMID- 26136720 TI - Examination of mechanisms underlying enhanced memory performance in action video game players: a pilot study. AB - Previous studies have shown enhanced memory performance resulting from extensive action video game playing. The mechanisms underlying the cognitive benefit were investigated in the current study. We presented two types of retro-cues, with variable intervals to memory array (Task 1) or test array (Task 2), during the retention interval in a change detection task. In Task 1, action video game players demonstrated steady performance while non-action video game players showed decreased performance as cues occurred later, indicating their performance difference increased as the cue-to-memory-array intervals became longer. In Task 2, both participant groups increased their performance at similar rates as cues presented later, implying the performance difference in two groups were irrespective of the test-array-to-cue intervals. These findings suggested that memory benefit from game plays is not attributable to the higher ability of overcoming interference from the test array, but to the interactions between the two processes of protection from decay and resistance from interference, or from alternative hypotheses. Implications for future studies were discussed. PMID- 26136721 TI - Individual differences in competent consumer choice: the role of cognitive reflection and numeracy skills. AB - In this paper, we investigate whether cognitive reflection and numeracy skills affect the quality of the consumers' decision-making process in a purchase decision context. In a first (field) experiment, an identical product was on sale in two shops with different initial prices and discounts. One of the two deals was better than the other and the consumers were asked to choose the best one and to describe which arithmetic operations they used to solve the problem; then they were asked to complete the numeracy scale (Lipkus et al., 2001). The choice procedures used by the consumers were classified as "complete decision approach" when all the arithmetic operations needed to solve the problem were computed, and as "partial decision approach" when only some operations were computed. A mediation model shows that higher numeracy is associated with use of the complete decision approach. In turn, this approach is positively associated with the quality of the purchase decision. Given that these findings highlight the importance of the decision processes, in a second (laboratory) experiment we used a supplementary method to study the type of information search used by the participants: eye-tracking. In this experiment the participants were presented with decision problems similar to those used in Experiment 1 and they completed the Lipkus numeracy scale and the Cognitive Reflection Test (CRT; Frederick, 2005). Participants with a high CRT score chose the best deal more frequently, and showed a more profound and detailed information search pattern compared to participants with a low CRT score. Overall, results indicate that higher levels of cognitive reflection and numeracy skills predict the use of a more thorough decision process (measured with two different techniques: retrospective verbal reports and eye movements). In both experiments the decision process is a crucial factor which greatly affects the quality of the purchase decision. PMID- 26136722 TI - Blast Overpressure Waves Induce Transient Anxiety and Regional Changes in Cerebral Glucose Metabolism and Delayed Hyperarousal in Rats. AB - Physiological alterations, anxiety, and cognitive disorders are strongly associated with blast-induced traumatic brain injury (blast TBI), and are common symptoms in service personnel exposed to blasts. Since 2006, 25,000-30,000 new TBI cases are diagnosed annually in U.S. Service members; increasing evidence confirms that primary blast exposure causes diffuse axonal injury and is often accompanied by altered behavioral outcomes. Behavioral and acute metabolic effects resulting from blast to the head in the absence of thoracic contributions from the periphery were examined, following a single blast wave directed to the head of male Sprague-Dawley rats protected by a lead shield over the torso. An 80 psi head blast produced cognitive deficits that were detected in working memory. Blast TBI rats displayed increased anxiety as determined by elevated plus maze at day 9 post-blast compared to sham rats; blast TBI rats spent significantly more time than the sham controls in the closed arms (p < 0.05; n = 8-11). Interestingly, anxiety symptoms were absent at days 22 and 48 post-blast. Instead, blast TBI rats displayed increased rearing behavior at day 48 post-blast compared to sham rats. Blast TBI rats also exhibited suppressed acoustic startle responses, but similar pre-pulse inhibition at day 15 post-blast compared to sham rats. Acute physiological alterations in cerebral glucose metabolism were determined by positron emission tomography 1 and 9 days post-blast using (18)F fluorodeoxyglucose ((18)F-FDG). Global glucose uptake in blast TBI rat brains increased at day 1 post-blast (p < 0.05; n = 4-6) and returned to sham levels by day 9. Our results indicate a transient increase in cerebral metabolism following a blast injury. Markers for reactive astrogliosis and neuronal damage were noted by immunoblotting motor cortex tissue from day 10 post-blast in blast TBI rats compared to sham controls (p < 0.05; n = 5-6). PMID- 26136723 TI - Cerebrospinal Fluid P-Tau181P: Biomarker for Improved Differential Dementia Diagnosis. AB - The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P) in the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid beta peptide of 42 amino acids (Abeta1-42), total tau protein (T-tau), and P tau181P were determined with single analyte ELISA-kits (INNOTEST((r)), Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUC) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests. The Abeta1-42/P-tau181P ratio (AUC = 0.770) performed significantly better than Abeta1-42 (AUC = 0.677, P = 0.004), T tau (AUC = 0.592, P < 0.001), and Abeta1-42/T-tau (AUC = 0.678, P = 0.001), while P-tau181P (AUC = 0.720) performed significantly better than T-tau (AUC = 0.592, P < 0.001) to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, Abeta1-42/P-tau181P (AUC = 0.894) discriminated AD from frontotemporal dementia significantly better than Abeta1-42 (AUC = 0.776, P = 0.020) and T-tau (AUC = 0.746, P = 0.004), while P-tau181P/T tau (AUC = 0.958) significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to Abeta1-42 (AUC = 0.688, P = 0.004), T tau (AUC = 0.874, P = 0.040), and Abeta1-42/P-tau181P (AUC = 0.760, P = 0.003). In conclusion, this study demonstrates P-tau181P is an essential component of the AD CSF biomarker panel, and combined assessment of Abeta1-42, T-tau, and P tau181P renders, to present date, the highest diagnostic power to discriminate between AD and non-AD dementias. PMID- 26136725 TI - Corrigendum: "Editorial: Neurological and Psychiatric Disorders in Endocrine Diseases". AB - [This corrects the article on p. 75 in vol. 6, PMID: 26029166.]. PMID- 26136724 TI - Salivary Function after Radioiodine Therapy: Poor Correlation between Symptoms and Salivary Scintigraphy. AB - OBJECTIVE: Symptoms of salivary gland dysfunction frequently develop after radioactive iodine (RAI) therapy, but have generally not been correlated with assessment of salivary gland functioning. The aim of this study was to determine whether there was a correlation between salivary symptoms and salivary functioning as assessed by salivary scan parameters. METHODS: This was a non randomized observational study. Fifteen patients receiving RAI therapy for differentiated thyroid cancer completed a questionnaire assessing their salivary and nasal symptoms prior to their therapy and 3 and 12 months after their therapy. Salivary gland scanning using technetium-99m pertechnetate was performed at the same time points. In addition, protective measures used at the time of radioiodine administration, such as use of fluids and sour candy, were also documented. Measures of salivary gland accumulation and secretion were correlated with scores of salivary and nasal symptomatology and any effects of protective measures were assessed. RESULTS: The mean number of salivary, nasal, and total symptoms at 3 months increased significantly over the number of symptoms at baseline by 3.7, 2.7, and 6.3 symptoms, respectively (p values 0.001, 0.0046, and <0.001, respectively). The mean increases in the number of salivary, nasal, and total symptoms at 12 months were non-significant at 1.3, 1.3, and 2.5 symptoms, respectively. The mean right parotid gland accumulation and secretion of radioisotope declined significantly at 3 months, compared with baseline. The changes in left parotid and right and left submandibular function were non significant. There was no association between the increase in salivary, nasal, or total symptoms and the change in scintigraphy measures. However, the increases in nasal and total symptoms were significantly greater in those with co-existent Hashimoto's disease, compared with those without this condition (p values 0.01 and 0.04, respectively). Nasal symptoms decreased (p value 0.04) and total symptoms trended to decrease (p value 0.08) in those who used sour candies, compared with those who did not. Increasing body mass index was significantly associated with increasing nasal symptoms (p value 0.05). Greater decline in salivary parameters at 3 months compared with baseline was generally associated with heavier body weight, decreased thyroid cancer stage, absence of Hashimoto's thyroiditis, and pre-menopausal status. CONCLUSION: Salivary and nasal symptoms increased and salivary scintigraphy parameters decreased after radioiodine therapy. However, the increased symptoms did not correlate with decrements in salivary gland accumulation or secretion. Moreover, the variables associated with symptoms and changes in salivary scan parameters differed. Therefore, a better understanding of the relationship between salivary gland symptoms and functioning is needed. Factors affecting susceptibility to salivary and nasal damage after radioiodine therapy need to be better elucidated, so that modifiable factors can be identified. PMID- 26136726 TI - Glucose-tolerant beta-glucosidase retrieved from a Kusaya gravy metagenome. AB - beta-glucosidases (BGLs) hydrolyze cello-oligosaccharides to glucose and play a crucial role in the enzymatic saccharification of cellulosic biomass. Despite their significance for the production of glucose, most identified BGLs are commonly inhibited by low (~mM) concentrations of glucose. Therefore, BGLs that are insensitive to glucose inhibition have great biotechnological merit. We applied a metagenomic approach to screen for such rare glucose-tolerant BGLs. A metagenomic library was created in Escherichia coli (~10,000 colonies) and grown on LB agar plates containing 5-bromo-4-chloro-3-indolyl-beta-D-glucoside, yielding 828 positive (blue) colonies. These were then arrayed in 96-well plates, grown in LB, and secondarily screened for activity in the presence of 10% (w/v) glucose. Seven glucose-tolerant clones were identified, each of which contained a single bgl gene. The genes were classified into two groups, differing by two nucleotides. The deduced amino acid sequences of these genes were identical (452 aa) and found to belong to the glycosyl hydrolase family 1. The recombinant protein (Ks5A7) was overproduced in E. coli as a C-terminal 6 * His-tagged protein and purified to apparent homogeneity. The molecular mass of the purified Ks5A7 was determined to be 54 kDa by SDS-PAGE, and 160 kDa by gel filtration analysis. The enzyme was optimally active at 45 degrees C and pH 5.0-6.5 and retained full or 1.5-2-fold enhanced activity in the presence of 0.1-0.5 M glucose. It had a low KM (78 MUM with p-nitrophenyl beta-D-glucoside; 0.36 mM with cellobiose) and high V max (91 MUmol min(-1) mg(-1) with p-nitrophenyl beta D-glucoside; 155 MUmol min(-1) mg(-1) with cellobiose) among known glucose tolerant BGLs and was free from substrate (0.1 M cellobiose) inhibition. The efficient use of Ks5A7 in conjunction with Trichoderma reesei cellulases in enzymatic saccharification of alkaline-treated rice straw was demonstrated by increased production of glucose. PMID- 26136727 TI - Small protein B upregulates sensor kinase bvgS expression in Aeromonas veronii. AB - Earlier studies reveal that Small protein B (SmpB), a class of well-conserved tmRNA-binding proteins, is essential for the trans-translation process, which functions as a system for translation surveillance and ribosome rescue. Here, we report a previously unrecognized mechanism by which SmpB alone positively regulates the expression of a sensor kinase, BvgS, in Aeromonas veronii. A reporter plasmid was constructed in which the promoter of bvgS was used to control the expression of the enhanced green fluorescent protein (eGFP) gene. When the reporter plasmid was co-transformed with a SmpB expression construct into E. coli, the relative fluorescence intensity increased about threefold. Transformation with a truncated form of smpB gene showed that the C-terminus had little effect, while N-terminus unexpectedly increased eGFP production. Next, a series of SmpB mutants were generated by site-directed mutagenesis. When the mutants SmpB (G11S) or SmpB (E32AG) was used in the experiment, eGFP expression dropped significantly compared with that of wild type SmpB. Further, purified SmpB was shown to bind the promoter regions of bvgS in the agarose gel retardation assay. Quantitative RT-PCR analysis showed that eGFP transcript levels increased approximately 25-fold in the presence of SmpB. Likewise, smpB knockout decreased bvgS transcripts significantly in A. veronii, and also displayed a reduced capability in salt tolerance. Collectively, the data presented here will facilitate a deeper understanding of SmpB-mediated regulatory circuits as a transcriptional factor in A. veronii. PMID- 26136728 TI - Biogenic selenium and tellurium nanoparticles synthesized by environmental microbial isolates efficaciously inhibit bacterial planktonic cultures and biofilms. AB - The present study deals with Se(0)- and Te(0)-based nanoparticles bio-synthesized by two selenite- and tellurite-reducing bacterial strains, namely Stenotrophomonas maltophilia SeITE02 and Ochrobactrum sp. MPV1, isolated from polluted sites. We evidenced that, by regulating culture conditions and exposure time to the selenite and tellurite oxyanions, differently sized zero-valent Se and Te nanoparticles were produced. The results revealed that these Se(0) and Te(0) nanoparticles possess antimicrobial and biofilm eradication activity against Escherichia coli JM109, Pseudomonas aeruginosa PAO1, and Staphylococcus aureus ATCC 25923. In particular, Se(0) nanoparticles exhibited antimicrobial activity at quite low concentrations, below that of selenite. Toxic effects of both Se(0) and Te(0) nanoparticles can be related to the production of reactive oxygen species upon exposure of the bacterial cultures. Evidence so far achieved suggests that the antimicrobial activity seems to be strictly linked to the dimensions of the nanoparticles: indeed, the highest activity was shown by nanoparticles of smaller sizes. In particular, it is worth noting how the bacteria tested in biofilm mode responded to the treatment by Se(0) and Te(0) nanoparticles with a susceptibility similar to that observed in planktonic cultures. This suggests a possible exploitation of both Se(0) and Te(0) nanoparticles as efficacious antimicrobial agents with a remarkable biofilm eradication capacity. PMID- 26136729 TI - Editorial for: Microbial symbiosis of marine sessile hosts- diversity and function. PMID- 26136730 TI - Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle. AB - Cefquinome is a fourth generation cephalosporin with antimicrobial activity against gram negative and gram positive bacterial species, including Staphylococcus aureus. The aim of our study was to observe the ex-vivo activity of cefquinome against Staphylococcus aureus strains by using bovine serum from intravenously treated cattle. Cefquinome kinetics were measured by liquid chromatography and UV detection. In vitro post antibiotic effects (PAEs) and mutant prevention concentrations were determined with S. aureus strain ATCC 12598. Cefquinome exhibited time-dependent killing and produced in vitro PAEs increasing with concentration and time of exposure. A pharmacokinetic pharmacodynamic model was established to simulate the efficacy of cefquinome for different dosage regimens. A dosage of 2 mg/kg every 12 h for 3 days was expected to reach a bactericidal activity against S. aureus in case of septicemia. PMID- 26136731 TI - Classes of organic molecules targeted by a methanogenic microbial consortium grown on sedimentary rocks of various maturities. AB - Organic-rich shales are populated by methanogenic consortia that are able to degrade the fossilized organic matter into methane gas. To identify the organic fraction effectively degraded, we have sequentially depleted two types of organic rich sedimentary rocks, shale, and coal, at two different maturities, by successive solvent extractions to remove the most soluble fractions (maltenes and asphaltenes) and isolate kerogen. We show the ability of the consortia to produce methane from all rock samples, including those containing the most refractory organic matter, i.e., the kerogen. Shales yielded higher methane production than lignite and coal. Mature rocks yielded more methane than immature rocks. Surprisingly, the efficiency of the consortia was not influenced by the removal of the easily biodegradable fractions contained in the maltenes and asphaltenes. This suggests that one of the limitations of organic matter degradation in situ may be the accessibility to the carbon and energy source. Indeed, bitumen has a colloidal structure that may prevent the microbial consortia from reaching the asphaltenes in the bulk rock. Solvent extractions might favor the access to asphaltenes and kerogen by modifying the spatial organization of the molecules in the rock matrix. PMID- 26136732 TI - When nanoparticles meet biofilms-interactions guiding the environmental fate and accumulation of nanoparticles. AB - Bacteria are essential components of all natural and many engineered systems. The most active fractions of bacteria are now recognized to occur as biofilms, where cells are attached and surrounded by a secreted matrix of "sticky" extracellular polymeric substances. Recent investigations have established that significant accumulation of nanoparticles (NPs) occurs in aquatic biofilms. These studies point to the emerging roles of biofilms for influencing partitioning and possibly transformations of NPs in both natural and engineered systems. While attached biofilms are efficient "sponges" for NPs, efforts to elucidate the fundamental mechanisms guiding interactions between NPs and biofilms have just begun. In this mini review, special attention is focused on NP-biofilm interactions within the aquatic environment. We highlight key physical, chemical, and biological processes that affect interactions and accumulation of NPs by bacterial biofilms. We posit that these biofilm processes present the likely possibility for unique biological and chemical transformations of NPs. Ultimately, the environmental fate of NPs is influenced by biofilms, and therefore requires a more in-depth understanding of their fundamental properties. PMID- 26136733 TI - Dryocrassin ABBA, a novel active substance for use against amantadine-resistant H5N1 avian influenza virus. AB - The occurrence of multi-drug resistant highly pathogenic avian influenza virus (HPAIV) strains highlights the urgent need for strategies for the prevention and control of avian influenza virus. The aim of our current study is to evaluate the antiviral activity of dryocrassin ABBA isolated from Rhizoma Dryopteridis Crassirhizomatis (RDC) against an amantadine-resistant H5N1 (A/Chicken/Hebei/706/2005) strain in a mouse model. Post inoculation with HPAIV H5N1 virus in mice, the survival rate was 87, 80, and 60% respectively in the 33, 18, and 12.5 mg/kg dryocrassin ABBA-treated groups. On the other hand, the survival rate was 53 and 20%, respectively in the amantadine-treated group and untreated group. Mice administered with dryocrassin ABBA or amantadine showed a significant weight increase compared to the untreated group. Moreover, 33 and 18 mg/kg dryocrassin ABBA have decreased lung index (P >0.05) and virus loads (P <0.01) compared to the untreated group on day 7. Also, on day 7 bronchoalveolar lavage fluid pro-inflammatory cytokines (IL-6, TNF-alpha, and IFN-gamma) decreased significantly (P <0.01) while anti-inflammatory cytokines (IL-10 and MCP-1) were increased significantly (P <0.01) in the 33 and 18 mg/kg dryocrassin ABBA-treated groups compared to the amantadine group and the untreated group. Moreover, the concentrations of IL-12 in drug-treated groups were significantly (P < 0.01) lowered compared with the untreated group. Based on the above we conclude that orally administered dryocrassin ABBA provided mice protection against avian influenza virus H5N1 by inhibiting inflammation and reducing virus loads. Dryocrassin ABBA is a potential novel lead compound which had antiviral effects on amantadine-resistant avian influenza virus H5N1 infection. PMID- 26136734 TI - Genomic comparison of closely related Giant Viruses supports an accordion-like model of evolution. AB - Genome gigantism occurs so far in Phycodnaviridae and Mimiviridae (order Megavirales). Origin and evolution of these Giant Viruses (GVs) remain open questions. Interestingly, availability of a collection of closely related GV genomes enabling genomic comparisons offer the opportunity to better understand the different evolutionary forces acting on these genomes. Whole genome alignment for five groups of viruses belonging to the Mimiviridae and Phycodnaviridae families show that there is no trend of genome expansion or general tendency of genome contraction. Instead, GV genomes accumulated genomic mutations over the time with gene gains compensating the different losses. In addition, each lineage displays specific patterns of genome evolution. Mimiviridae (megaviruses and mimiviruses) and Chlorella Phycodnaviruses evolved mainly by duplications and losses of genes belonging to large paralogous families (including movements of diverse mobiles genetic elements), whereas Micromonas and Ostreococcus Phycodnaviruses derive most of their genetic novelties thought lateral gene transfers. Taken together, these data support an accordion-like model of evolution in which GV genomes have undergone successive steps of gene gain and gene loss, accrediting the hypothesis that genome gigantism appears early, before the diversification of the different GV lineages. PMID- 26136735 TI - Increased prevalence of carbapenem resistant Enterobacteriaceae in hospital setting due to cross-species transmission of the bla NDM-1 element and clonal spread of progenitor resistant strains. AB - This study investigated the transmission characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains collected from a hospital setting in China, in which consistent emergence of CRE strains were observable during the period of May 2013 to February 2014. Among the 45 CRE isolates tested, 21 (47%) strains were found to harbor the bla NDM-1 element, and the rest of 24 CRE strains were all positive for bla KPC-2. The 21 bla NDM-1-borne strains were found to comprise multiple Enterobacteriaceae species including nine Enterobacter cloacae, three Escherichia coli, three Citrobacter freundii, two Klebsiella pneumoniae, two Klebsiella oxytoca, and two Morganella morganii strains, indicating that cross species transmission of bla NDM-1 is a common event. Genetic analyses by PFGE and MLST showed that, with the exception of E. coli and E. cloacae, strains belonging to the same species were often genetically unrelated. In addition to bla NDM-1, several CRE strains were also found to harbor the bla KPC-2, bla VIM-1, and bla IMP-4 elements. Conjugations experiments confirmed that the majority of carbapenem resistance determinants were transferable. Taken together, our findings suggest that transmission of mobile resistance elements among members of Enterobacteriaceae and clonal spread of CRE strains may contribute synergistically to a rapid increase in the population of CRE in clinical settings, prompting a need to implement more rigorous infection control measures to arrest such vicious transmission cycle in CRE-prevalent areas. PMID- 26136736 TI - A transient resistance to blood-stage malaria in interferon-gamma-deficient mice through impaired production of the host cells preferred by malaria parasites. AB - IFN-gamma plays both pathological and protective roles during blood-stage malaria. One of its pathological roles is its contribution to anemia by suppressing erythropoiesis. Here, to evaluate the effects of IFN-gamma-mediated alterations in erythropoiesis on the course of malaria infection, mice deficient in IFN-gamma (GKO) were infected with two strains of the rodent malaria parasite Plasmodium yoelii, 17XL (PyL) and 17XNL (PyNL), whose host cell ranges differ. Regardless of genotype, all mice infected with PyL, which can invade any erythrocyte, developed high parasitemia and died quickly. Although PyNL caused a transient non-lethal infection in wild-type (WT) mice, some GKO mice were unable to control the infection and died. However, GKO mice were resistant to the early phase of infection, showing an impaired increase in parasitemia compared with WT mice. This resistance in the GKO mice was associated with having significantly fewer reticulocytes, which are the preferred host cells for PyNL parasites, than the WT mice. Compared with the amount of reticulocytes in GKO mice during the early stages of infection, there was a significant increase in the amount of these cells at later stages, which coincided with the inability of these mice to control the infection. We found that the growth of PyNL parasites correlated with the amount of reticulocytes. Thus, the reduced number of reticulocytes in mice lacking IFN-gamma appears to be responsible for the limited parasite growth. Notably, these differences in GKO mice were at least partially reversed when the mice were injected with exogenous IFN-gamma. Additionally, an artificial induction of hemolytic anemia and an increase in reticulocytes by phenylhydrazine treatment in GKO mice completely abolished the lower parasitemia and resistance during early phase infection. These results suggest that IFN-gamma may contribute to the early growth of PyNL parasites by increasing the amount of reticulocytes, presumably by enhancing erythropoiesis. PMID- 26136737 TI - Multi-color imaging of the bacterial nucleoid and division proteins with blue, orange, and near-infrared fluorescent proteins. AB - Studies of the spatiotemporal protein dynamics within live bacterial cells impose a strong demand for multi-color imaging. Despite the increasingly large collection of fluorescent protein (FP) variants engineered to date, only a few of these were successfully applied in bacteria. Here, we explore the performance of recently engineered variants with the blue (TagBFP), orange (TagRFP-T, mKO2), and far-red (mKate2) spectral colors by tagging HU, LacI, MinD, and FtsZ for visualizing the nucleoid and the cell division process. We find that, these FPs outperformed previous versions in terms of brightness and photostability at their respective spectral range, both when expressed as cytosolic label and when fused to native proteins. As this indicates that their folding is sufficiently fast, these proteins thus successfully expand the applicable spectra for multi-color imaging in bacteria. A near-infrared protein (eqFP670) is found to be the most red-shifted protein applicable to bacteria so far, with brightness and photostability that are advantageous for cell-body imaging, such as in microfluidic devices. Despite the multiple advantages, we also report the alarming observation that TagBFP directly interacts with TagRFP-T, causing interference of localization patterns between their fusion proteins. Our application of diverse FPs for endogenous tagging provides guidelines for future engineering of fluorescent fusions in bacteria, specifically: (1) The performance of newly developed FPs should be quantified in vivo for their introduction into bacteria; (2) spectral crosstalk and inter-variant interactions between FPs should be carefully examined for multi-color imaging; and (3) successful genomic fusion to the 5(')-end of a gene strongly depends on the translational read through of the inserted coding sequence. PMID- 26136738 TI - Catabolic and regulatory systems in Shewanella oneidensis MR-1 involved in electricity generation in microbial fuel cells. AB - Shewanella oneidensis MR-1 is a facultative anaerobe that respires using a variety of inorganic and organic compounds. MR-1 is also capable of utilizing extracellular solid materials, including anodes in microbial fuel cells (MFCs), as electron acceptors, thereby enabling electricity generation. As MFCs have the potential to generate electricity from biomass waste and wastewater, MR-1 has been extensively studied to identify the molecular systems that are involved in electricity generation in MFCs. These studies have demonstrated the importance of extracellular electron-transfer (EET) pathways that electrically connect the quinone pool in the cytoplasmic membrane to extracellular electron acceptors. Electricity generation is also dependent on intracellular catabolic pathways that oxidize electron donors, such as lactate, and regulatory systems that control the expression of genes encoding the components of catabolic and electron-transfer pathways. In addition, recent findings suggest that cell-surface polymers, e.g., exopolysaccharides, and secreted chemicals, which function as electron shuttles, are also involved in electricity generation. Despite these advances in our knowledge on the EET processes in MR-1, further efforts are necessary to fully understand the underlying intra- and extracellular molecular systems for electricity generation in MFCs. We suggest that investigating how MR-1 coordinates these systems to efficiently transfer electrons to electrodes and conserve electrochemical energy for cell proliferation is important for establishing the biological basis for MFCs. PMID- 26136739 TI - Redefining bacterial origins of replication as centralized information processors. AB - In this review we stress the differences between eukaryotes and bacteria with respect to their different cell cycles, replication mechanisms and genome organizations. One of the most basic and underappreciated differences is that a bacterial chromosome uses only one ori while eukaryotic chromosome uses multiple oris. Consequently, eukaryotic oris work redundantly in a cell cycle divided into separate phases: First inactive replication proteins assemble on eukaryotic oris, and then they await conditions (in the separate "S-phase") that activate only the ori-bound and pre-assembled replication proteins. S-phase activation (without re assembly) ensures that a eukaryotic ori "fires" (starts replication) only once and that each chromosome consistently duplicates only once per cell cycle. This precise chromosome duplication does not require precise multiple ori firing in S phase. A eukaryotic ori can fire early, late or not at all. The single bacterial ori has no such margin for error and a comparable imprecision is lethal. Single ori usage is not more primitive; it is a totally different strategy that distinguishes bacteria. We further argue that strong evolutionary pressures created more sophisticated single ori systems because bacteria experience extreme and rapidly changing conditions. A bacterial ori must rapidly receive and process much information in "real-time" and not just in "cell cycle time." This redefinition of bacterial oris as centralized information processors makes at least two important predictions: First that bacterial oris use many and yet to be discovered control mechanisms and second that evolutionarily distinct bacteria will use many very distinct control mechanisms. We review recent literature that supports both predictions. We will highlight three key examples and describe how negative-feedback, phospho-relay, and chromosome-partitioning systems act to regulate chromosome replication. We also suggest future studies and discuss using replication proteins as novel antibiotic targets. PMID- 26136740 TI - Antimicrobial food packaging: potential and pitfalls. AB - Nowadays food preservation, quality maintenance, and safety are major growing concerns of the food industry. It is evident that over time consumers' demand for natural and safe food products with stringent regulations to prevent food-borne infectious diseases. Antimicrobial packaging which is thought to be a subset of active packaging and controlled release packaging is one such promising technology which effectively impregnates the antimicrobial into the food packaging film material and subsequently delivers it over the stipulated period of time to kill the pathogenic microorganisms affecting food products thereby increasing the shelf life to severe folds. This paper presents a picture of the recent research on antimicrobial agents that are aimed at enhancing and improving food quality and safety by reduction of pathogen growth and extension of shelf life, in a form of a comprehensive review. Examination of the available antimicrobial packaging technologies is also presented along with their significant impact on food safety. This article entails various antimicrobial agents for commercial applications, as well as the difference between the use of antimicrobials under laboratory scale and real time applications. Development of resistance amongst microorganisms is considered as a future implication of antimicrobials with an aim to come up with actual efficacies in extension of shelf life as well as reduction in bacterial growth through the upcoming and promising use of antimicrobials in food packaging for the forthcoming research down the line. PMID- 26136741 TI - The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis. AB - A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed. PMID- 26136742 TI - The complex relationship between microbial growth rate and yield and its implications for ecosystem processes. PMID- 26136743 TI - MR1-Restricted Mucosal-Associated Invariant T Cells and Their Activation during Infectious Diseases. AB - MR1-restricted mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites, which are generated by a broad range of bacteria, from Escherichia coli to Mycobacterium tuberculosis and BCG. MAIT cells have been described as innate sensors of infection as they accumulate early in infected tissues. MAIT cells maintain an activated phenotype throughout the course of infections, secrete inflammatory cytokines, and have the potential to directly kill infected cells, playing an important role in shaping the host response. In this review, we will discuss the current knowledge regarding the molecular mechanisms that underline MAIT cells activation in sterile and non-sterile inflammatory conditions. PMID- 26136746 TI - Can Selective MHC Downregulation Explain the Specificity and Genetic Diversity of NK Cell Receptors? AB - Natural killer (NK) cells express inhibiting receptors (iNKRs), which specifically bind MHC-I molecules on the surface of healthy cells. When the expression of MHC-I on the cell surface decreases, which might occur during certain viral infections and cancer, iNKRs lose inhibiting signals and the infected cells become target for NK cell activation (missing-self detection). Although the detection of MHC-I deficient cells can be achieved by conserved receptor-ligand interactions, several iNKRs are encoded by gene families with a remarkable genetic diversity, containing many haplotypes varying in gene content and allelic polymorphism. So far, the biological function of this expansion within the NKR cluster has remained poorly understood. Here, we investigate whether the evolution of diverse iNKRs genes can be driven by a specific viral immunoevasive mechanism: selective MHC downregulation. Several viruses, including EBV, CMV, and HIV, decrease the expression of MHC-I to escape from T cell responses. This downregulation does not always affect all MHC loci in the same way, as viruses target particular MHC molecules. To study the selection pressure of selective MHC downregulation on iNKRs, we have developed an agent-based model simulating an evolutionary scenario of hosts infected with herpes-like viruses, which are able to selectively downregulate the expression of MHC-I molecules on the cell surface. We show that iNKRs evolve specificity and, depending on the similarity of MHC alleles within each locus and the differences between the loci, they can specialize to a particular MHC-I locus. The easier it is to classify an MHC allele to its locus, the lower the required diversity of the NKRs. Thus, the diversification of the iNKR cluster depends on the locus specific MHC structure. PMID- 26136745 TI - Polyomavirus-Specific Cellular Immunity: From BK-Virus-Specific Cellular Immunity to BK-Virus-Associated Nephropathy? AB - In renal transplantation, BK-virus (BKV)-associated nephropathy has emerged as a major complication, with a prevalence of 1-10% and graft loss in >50% of cases. BKV is a member of the polyomavirus family and rarely induces apparent clinical disease in the general population. However, replication of polyomaviruses, associated with significant organ disease, is observed in patients with acquired immunosuppression. Monitoring of specific immunity combined with viral load could be used to individually assess the risk of viral reactivation and virus control. We review the current knowledge on BKV-specific cellular immunity and, more specifically, in immunocompromised patients. In the future, immune-based therapies could allow us to treat and prevent BKV-associated nephropathy. PMID- 26136744 TI - Revealing the Mechanisms of Protein Disorder and N-Glycosylation in CD44 Hyaluronan Binding Using Molecular Simulation. AB - The extracellular N-terminal hyaluronan binding domain (HABD) of CD44 is a small globular domain that confers hyaluronan (HA) binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA-binding site from a low affinity to a high affinity state; in the partially disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD. PMID- 26136747 TI - Editorial: Carbohydrates: The Yet to be Tasted Sweet Spot of Immunity. PMID- 26136748 TI - Type II NKT Cells in Inflammation, Autoimmunity, Microbial Immunity, and Cancer. AB - Natural killer T cells (NKT) recognize self and microbial lipid antigens presented by non-polymorphic CD1d molecules. Two major NKT cell subsets, type I and II, express different types of antigen receptors (TCR) with distinct mode of CD1d/lipid recognition. Though type II NKT cells are less frequent in mice and difficult to study, they are predominant in human. One of the major subsets of type II NKT cells reactive to the self-glycolipid sulfatide is the best characterized and has been shown to induce a dominant immune regulatory mechanism that controls inflammation in autoimmunity and in anti-cancer immunity. Recently, type II NKT cells reactive to other self-glycolipids and phospholipids have been identified suggesting both promiscuous and specific TCR recognition in microbial immunity as well. Since the CD1d pathway is highly conserved, a detailed understanding of the biology and function of type II NKT cells as well as their interplay with type I NKT cells or other innate and adaptive T cells will have major implications for potential novel interventions in inflammatory and autoimmune diseases, microbial immunity, and cancer. PMID- 26136749 TI - Cytokine Levels in Late Pregnancy: Are Female Infants Better Protected Against Inflammation? AB - Inflammatory responses have been implicated in several forms of infant deaths (sudden expected deaths and stillbirths) and the initiation of pre-term births. In this study, we examined matched samples of term maternal blood, cord blood, and amniotic fluid obtained from 24 elective cesarean deliveries for both pro- and anti-inflammatory cytokines thought to be important in maintaining a balanced response leading to successful pregnancy outcome. These included interleukin (IL) 1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN gamma), IL-10, and IL-1 receptor antagonist (IL-1ra). Amniotic fluid levels for each of the cytokines examined were significantly higher than those for cord blood or maternal plasma. While pro-inflammatory cytokines were higher in amniotic fluid associated with male fetuses compared with females, the major significant difference was higher levels of IL-1ra in amniotic fluid associated with female fetuses. Our study supports similar findings for cytokines during mid trimester, which noted that amniotic fluid levels were higher than those in maternal blood. Our study suggests that maternal decidua secretes additional IL ra in the presence of a female conceptus which improves the likelihood of a good outcome compared to pregnancies with male fetuses. PMID- 26136750 TI - Cellular Regulation of the Uterine Microenvironment That Enables Embryo Implantation. AB - Implantation of the fertilized egg into the maternal uterus is a crucial step in pregnancy establishment. Increasing evidence suggests that its success depends on various cell types of the innate immune system and on the fine balance between inflammatory and anti-inflammatory processes. In addition, it has recently been established that regulatory T cells play a superordinate role in dictating the quality of uterine environment required for successful pregnancy. Here, we discuss the cellular regulation of uterine receptivity with emphasis on the function and regulation of cells from the innate and adaptive immune system. PMID- 26136752 TI - Integration of the proteome and transcriptome reveals multiple levels of gene regulation in the rice dl2 mutant. AB - Leaf vascular system differentiation and venation patterns play a key role in transporting nutrients and maintaining the plant shape, which is an important agronomic trait for improving photosynthetic efficiency. However, there is little knowledge about the regulation of leaf vascular specification and development. Here we utilized the rice midribless mutant (dl2) to investigate the molecular changes in transcriptome and proteome profiles during leaf vascular specification and differentiation. Using isobaric tags for relative and absolute quantification (iTRAQ) with digital gene expression (DGE) techniques, a nearly complete catalog of expressed protein and mRNA was acquired. From the catalog, we reliably identified 3172 proteins and 9,865,230 tags mapped to genes, and subsets of 141 proteins and 98 mRNAs, which were differentially expressed between the dl2 mutant and wild type. The correlation analysis between the abundance of differentially expressed mRNA and DEPs (differentially expressed proteins) revealed numerous discordant changes in mRNA/protein pairs and only a modest correlation was observed, indicative of divergent regulation of transcription and translational processes. The DEPs were analyzed for their involvement in biological processes and metabolic pathways. Up- or down- regulation of some key proteins confirmed that the physiological process of vascular differentiation is an active process. These key proteins included those not previously reported to be associated with vascular differentiation processes, and included proteins that are involved in the spliceosome pathway. Together, our results show that the developmental and physiological process of the leaf vascular system is a thoroughly regulated and complicated process and this work has identified potential targets for genetic modification that could be used to regulate the development of the leaf vasculature. PMID- 26136753 TI - Gel-based proteomics in plants: time to move on from the tradition. PMID- 26136754 TI - Conservation of AtTZF1, AtTZF2, and AtTZF3 homolog gene regulation by salt stress in evolutionarily distant plant species. AB - Arginine-rich tandem zinc-finger proteins (RR-TZF) participate in a wide range of plant developmental processes and adaptive responses to abiotic stress, such as cold, salt, and drought. This study investigates the conservation of the genes AtTZF1-5 at the level of their sequences and expression across plant species. The genomic sequences of the two RR-TZF genes TdTZF1-A and TdTZF1-B were isolated in durum wheat and assigned to chromosomes 3A and 3B, respectively. Sequence comparisons revealed that they encode proteins that are highly homologous to AtTZF1, AtTZF2, and AtTZF3. The expression profiles of these RR-TZF durum wheat and Arabidopsis proteins support a common function in the regulation of seed germination and responses to abiotic stress. In particular, analysis of plants with attenuated and overexpressed AtTZF3 indicate that AtTZF3 is a negative regulator of seed germination under conditions of salt stress. Finally, comparative sequence analyses establish that the RR-TZF genes are encoded by lower plants, including the bryophyte Physcomitrella patens and the alga Chlamydomonas reinhardtii. The regulation of the Physcomitrella AtTZF1-2-3-like genes by salt stress strongly suggests that a subgroup of the RR-TZF proteins has a function that has been conserved throughout evolution. PMID- 26136755 TI - Stress memory induced rearrangements of HSP transcription, photosystem II photochemistry and metabolism of tall fescue (Festuca arundinacea Schreb.) in response to high-temperature stress. AB - When plants are pre-exposed to stress, they can produce some stable signals and physiological reactions that may be carried forward as "stress memory". However, there is insufficient information about plants' stress memory responses mechanisms. Here, two tall fescue genotypes, heat-tolerant PI 574522 and heat sensitive PI 512315, were subjected to recurring high-temperature pre-acclimation treatment. Two heat shock protein (HSP) genes, LMW-HSP and HMW-HSP, exhibited transcriptional memory for their higher transcript abundance during one or more subsequent stresses (S2, S3, S4) relative to the first stress (S1), and basal transcript levels during the recovery states (R1, R2, and R3). Activated transcriptional memory from two trainable genes could persist up to 4 days, and induce higher thermotolerance in tall fescue. This was confirmed by greater turf quality and lower electrolyte leakage. Pre-acclimation treatment inhibited the decline at steps of O-J-I-P and energy transport fluxes in active Photosystem II reaction center (PSII RC) for both tall fescue genotypes. The heat stress memory was associated with major shifts in leaf metabolite profiles. Furthermore, there was an exclusive increase in leaf organic acids (citric acid, malic acid, tris phosphoric acid, threonic acid), sugars (sucrose, glucose, idose, allose, talose, glucoheptose, tagatose, psicose), amino acids (serine, proline, pyroglutamic acid, glycine, alanine), and one fatty acid (butanoic acid) in pre-acclimated plants. These observations involved in transcriptional memory, PSII RC energy transport and metabolite profiles could provide new insights into the plant high temperature response process. PMID- 26136751 TI - Antigen Presentation, Autoantigens, and Immune Regulation in Multiple Sclerosis and Other Autoimmune Diseases. AB - Antigen presentation is in the center of the immune system, both in host defense against pathogens, but also when the system is unbalanced and autoimmune diseases like multiple sclerosis (MS) develop. It is not just by chance that a major histocompatibility complex gene is the major genetic susceptibility locus in MS; a feature that MS shares with other autoimmune diseases. The exact etiology of the disease, however, has not been fully understood yet. T cells are regarded as the major players in the disease, but most probably a complex interplay of altered central and peripheral tolerance mechanisms, T-cell and B-cell functions, characteristics of putative autoantigens, and a possible interference of environmental factors like microorganisms are at work. In this review, new data on all these different aspects of antigen presentation and their role in MS will be discussed, probable autoantigens will be summarized, and comparisons to other autoimmune diseases will be drawn. PMID- 26136757 TI - Influence of biochar, mycorrhizal inoculation, and fertilizer rate on growth and flowering of Pelargonium (Pelargonium zonale L.) plants. AB - Peat is the most common substrate used in nurseries despite being a very expensive and a non-renewable material. Peat replacement with biochar could be a sound environmental practice, as it is produced from waste biomass, but evaluation of biochar as a potting substrate is needed. Ratios of peat:biochar of 100:0, 70:30, 30:70 (BC0, BC30, and BC70, respectively), two fertilizer rates (FERT1, FERT2), and arbuscular mycorrhizal fungi (AMF) inoculation were tested on potted Pelargonium plants. Plant growth, flowering, bio-physiological and nutritional responses, and root mycorrhization were evaluated. The BC30 mixture did not affect plant growth compared with pure peat. However, BC30 in combination with FERT2 treatment was more effective in enhancing nitrogen (N) and chlorophyll (CHL) leaf concentrations, and leaf and flower numbers. The BC70 mixture depressed plant growth, flowering traits, and root mycorrhization. Leaf N concentration was below the sufficiency range reported for Pelargonium growth. Leaf concentration of phosphorous (P) was adequate in pure peat and in BC30 but it dropped close to sub-optimal values in BC70. The pH value of the mixtures lowered P availability, though in BC30 the mycorrhizal activity could have allowed adequate P plant uptake. In BC70 plants, the deficiency of both N and P might be a reason for the observed growth reduction. The inoculation of the substrate with selected AMF improved plant growth (higher dry biomass, greater floral clusters, larger and more abundant leaves) and quality resulting in unstressed (lower electrolyte leakage and higher relative water content values) and greener leaves (low L(*) and C(*), high CHL content) and in more intensely colored flowers. We conclude that biochar can be applied in nursery/potted plant production provided that the proportion in the peat mixture does not exceed 30%. Furthermore, AMF inoculation contributed to achieving the best plant performance in 30% biochar amended medium. PMID- 26136756 TI - Hydrogen peroxide priming modulates abiotic oxidative stress tolerance: insights from ROS detoxification and scavenging. AB - Plants are constantly challenged by various abiotic stresses that negatively affect growth and productivity worldwide. During the course of their evolution, plants have developed sophisticated mechanisms to recognize external signals allowing them to respond appropriately to environmental conditions, although the degree of adjustability or tolerance to specific stresses differs from species to species. Overproduction of reactive oxygen species (ROS; hydrogen peroxide, H2O2; superoxide, [Formula: see text]; hydroxyl radical, OH(?) and singlet oxygen, (1)O2) is enhanced under abiotic and/or biotic stresses, which can cause oxidative damage to plant macromolecules and cell structures, leading to inhibition of plant growth and development, or to death. Among the various ROS, freely diffusible and relatively long-lived H2O2 acts as a central player in stress signal transduction pathways. These pathways can then activate multiple acclamatory responses that reinforce resistance to various abiotic and biotic stressors. To utilize H2O2 as a signaling molecule, non-toxic levels must be maintained in a delicate balancing act between H2O2 production and scavenging. Several recent studies have demonstrated that the H2O2-priming can enhance abiotic stress tolerance by modulating ROS detoxification and by regulating multiple stress-responsive pathways and gene expression. Despite the importance of the H2O2-priming, little is known about how this process improves the tolerance of plants to stress. Understanding the mechanisms of H2O2-priming induced abiotic stress tolerance will be valuable for identifying biotechnological strategies to improve abiotic stress tolerance in crop plants. This review is an overview of our current knowledge of the possible mechanisms associated with H2O2-induced abiotic oxidative stress tolerance in plants, with special reference to antioxidant metabolism. PMID- 26136758 TI - Phosphoproteomics technologies and applications in plant biology research. AB - Protein phosphorylation has long been recognized as an essential mechanism to regulate many important processes of plant life. However, studies on phosphorylation mediated signaling events in plants are challenged with low stoichiometry and dynamic nature of phosphorylated proteins. Significant advances in mass spectrometry based phosphoproteomics have taken place in recent decade, including phosphoprotein/phosphopeptide enrichment, detection and quantification, and phosphorylation site localization. This review describes a variety of separation and enrichment methods for phosphoproteins and phosphopeptides, the applications of technological innovations in plant phosphoproteomics, and highlights significant achievement of phosphoproteomics in the areas of plant signal transduction, growth and development. PMID- 26136759 TI - Comparative genomics of a cannabis pathogen reveals insight into the evolution of pathogenicity in Xanthomonas. AB - Pathogenic bacteria in the genus Xanthomonas cause diseases on over 350 plant species, including cannabis (Cannabis sativa L.). Because of regulatory limitations, the biology of the Xanthomonas-cannabis pathosystem remains largely unexplored. To gain insight into the evolution of Xanthomonas strains pathogenic to cannabis, we sequenced the genomes of two geographically distinct Xanthomonas strains, NCPPB 3753 and NCPPB 2877, which were previously isolated from symptomatic plant tissue in Japan and Romania. Comparative multilocus sequence analysis of housekeeping genes revealed that they belong to Group 2, which comprises most of the described species of Xanthomonas. Interestingly, both strains lack the Hrp Type III secretion system and do not contain any of the known Type III effectors. Yet their genomes notably encode two key Hrp pathogenicity regulators HrpG and HrpX, and hrpG and hrpX are in the same genetic organization as in the other Group 2 xanthomonads. Promoter prediction of HrpX regulated genes suggests the induction of an aminopeptidase, a lipase and two polygalacturonases upon plant colonization, similar to other plant-pathogenic xanthomonads. Genome analysis of the distantly related Xanthomonas maliensis strain 97M, which was isolated from a rice leaf in Mali, similarly demonstrated the presence of HrpG, HrpX, and a HrpX-regulated polygalacturonase, and the absence of the Hrp Type III secretion system and known Type III effectors. Given the observation that some Xanthomonas strains across distinct taxa do not contain hrpG and hrpX, we speculate a stepwise evolution of pathogenicity, which involves (i) acquisition of key regulatory genes and cell wall-degrading enzymes, followed by (ii) acquisition of the Hrp Type III secretion system, which is ultimately accompanied by (iii) successive acquisition of Type III effectors. PMID- 26136760 TI - Cytological and proteomic analyses of horsetail (Equisetum arvense L.) spore germination. AB - Spermatophyte pollen tubes and root hairs have been used as single-cell-type model systems to understand the molecular processes underlying polar growth of plant cells. Horsetail (Equisetum arvense L.) is a perennial herb species in Equisetopsida, which creates separately growing spring and summer stems in its life cycle. The mature chlorophyllous spores produced from spring stems can germinate without dormancy. Here we report the cellular features and protein expression patterns in five stages of horsetail spore germination (mature spores, rehydrated spores, double-celled spores, germinated spores, and spores with protonemal cells). Using 2-DE combined with mass spectrometry, 80 proteins were found to be abundance changed upon spore germination. Among them, proteins involved in photosynthesis, protein turnover, and energy supply were over represented. Thirteen proteins appeared as proteoforms on the gels, indicating the potential importance of post-translational modification. In addition, the dynamic changes of ascorbate peroxidase, peroxiredoxin, and dehydroascorbate reductase implied that reactive oxygen species homeostasis is critical in regulating cell division and tip-growth. The time course of germination and diverse expression patterns of proteins in photosynthesis, energy supply, lipid and amino acid metabolism indicated that heterotrophic and autotrophic metabolism were necessary in light-dependent germination of the spores. Twenty-six proteins were involved in protein synthesis, folding, and degradation, indicating that protein turnover is vital to spore germination and rhizoid tip-growth. Furthermore, the altered abundance of 14-3-3 protein, small G protein Ran, actin, and caffeoyl-CoA O-methyltransferase revealed that signaling transduction, vesicle trafficking, cytoskeleton dynamics, and cell wall modulation were critical to cell division and polar growth. These findings lay a foundation toward understanding the molecular mechanisms underlying fern spore asymmetric division and rhizoid polar growth. PMID- 26136761 TI - Cell wall composition and digestibility alterations in Brachypodium distachyon achieved through reduced expression of the UDP-arabinopyranose mutase. AB - Nucleotide-activated sugars are essential substrates for plant cell-wall carbohydrate-polymer biosynthesis. The most prevalent grass cell wall (CW) sugars are glucose (Glc), xylose (Xyl), and arabinose (Ara). These sugars are biosynthetically related via the UDP-sugar interconversion pathway. We sought to target and generate UDP-sugar interconversion pathway transgenic Brachypodium distachyon lines resulting in CW carbohydrate composition changes with improved digestibility and normal plant stature. Both RNAi-mediated gene-suppression and constitutive gene-expression approaches were performed. CWs from 336 T0 transgenic plants with normal appearance were screened for complete carbohydrate composition. RNAi mutants of BdRGP1, a UDP-arabinopyranose mutase, resulted in large alterations in CW carbohydrate composition with significant decreases in CW Ara content but with minimal change in plant stature. Five independent RNAi-RGP1 T1 plant lines were used for in-depth analysis of plant CWs. Real-time PCR analysis indicated that gene expression levels for BdRGP1, BdRGP2, and BdRGP3 were reduced in RNAi-RGP1 plants to 15-20% of controls. CW Ara content was reduced by 23-51% of control levels. No alterations in CW Xyl and Glc content were observed. Corresponding decreases in CW ferulic acid (FA) and ferulic acid dimers (FA-dimers) were observed. Additionally, CW p-coumarates (pCA) were decreased. We demonstrate the CW pCA decrease corresponds to Ara-coupled pCA. Xylanase-mediated digestibility of RNAi-RGP1 Brachypodium CWs resulted in a near twofold increase of released total carbohydrate. However, cellulolytic hydrolysis of CW material was inhibited in leaves of RNAi-RGP1 mutants. Our results indicate that targeted manipulation of UDP-sugar biosynthesis can result in biomass with substantially altered compositions and highlights the complex effect CW composition has on digestibility. PMID- 26136762 TI - The complete chloroplast genome sequence of the relict woody plant Metasequoia glyptostroboides Hu et Cheng. AB - Metasequoia glyptostroboides Hu et Cheng is the only species in the genus Metasequoia Miki ex Hu et Cheng, which belongs to the Cupressaceae family. There were around 10 species in the Metasequoia genus, which were widely spread across the Northern Hemisphere during the Cretaceous of the Mesozoic and in the Cenozoic. M. glyptostroboides is the only remaining representative of this genus. Here, we report the complete chloroplast (cp) genome sequence and the cp genomic features of M. glyptostroboides. The M. glyptostroboides cp genome is 131,887 bp in length, with a total of 117 genes comprised of 82 protein-coding genes, 31 tRNA genes and four rRNA genes. In this genome, 11 forward repeats, nine palindromic repeats, and 15 tandem repeats were detected. A total of 188 perfect microsatellites were detected through simple sequence repeat (SSR) analysis and these were distributed unevenly within the cp genome. Comparison of the cp genome structure and gene order to those of several other land plants indicated that a copy of the inverted repeat (IR) region, which was found to be IR region A (IRA), was lost in the M. glyptostroboides cp genome. The five most divergent and five most conserved genes were determined and further phylogenetic analysis was performed among plant species, especially for related species in conifers. Finally, phylogenetic analysis demonstrated that M. glyptostroboides is a sister species to Cryptomeria japonica (L. F.) D. Don and to Taiwania cryptomerioides Hayata. The complete cp genome sequence information of M. glyptostroboides will be great helpful for further investigations of this endemic relict woody plant and for in-depth understanding of the evolutionary history of the coniferous cp genomes, especially for the position of M. glyptostroboides in plant systematics and evolution. PMID- 26136764 TI - Distinct physiological responses of tomato and cucumber plants in silicon mediated alleviation of cadmium stress. AB - The alleviative effects of silicon (Si) on cadmium (Cd) toxicity were investigated in cucumber (Cucumis sativus L.) and tomato (Solanum lycopersicum L.) grown hydroponically. The growth of both plant species was inhibited by 100 MUM Cd, but Si application counteracted the adverse effects on growth. Si application significantly decreased the Cd concentrations in shoots of both species and roots of cucumber. The root-to-shoot transport of Cd was depressed by added Si in tomato whereas it was increased by added Si in cucumber. The total content of organic acids was decreased in tomato leaves but increased in cucumber roots and leaves by Si application under Cd stress. Si application also increased the cell wall polysaccharide levels in the roots of both species under Cd toxicity. Si-mediated changes in levels of organic acids and cell wall polysaccharides might contribute to the differences in Cd transport in the two species. In addition, Si application also mitigated Cd-induced oxidative damage in both species. The results indicate that there were different mechanisms for Si mediated decrease in shoot Cd accumulation: in tomato, Si supply decreased root to-shoot Cd transport; whereas in cucumber, Si supply reduced the Cd uptake by roots. It is suggested that Si-mediated Cd tolerance is associated with different physiological responses in tomato and cucumber plants. PMID- 26136763 TI - NPK macronutrients and microRNA homeostasis. AB - Macronutrients are essential elements for plant growth and development. In natural, non-cultivated systems, the availability of macronutrients is not a limiting factor of growth, due to fast recycling mechanisms. However, their availability might be an issue in modern agricultural practices, since soil has been frequently over exploited. From a crop management perspective, the nitrogen (N), phosphorus (P), and potassium (K) are three important limiting factors and therefore frequently added as fertilizers. NPK are among the nutrients that have been reported to alter post-embryonic root developmental processes and consequently, impairs crop yield. To cope with nutrients scarcity, plants have evolved several mechanisms involved in metabolic, physiological, and developmental adaptations. In this scenario, microRNAs (miRNAs) have emerged as additional key regulators of nutrients uptake and assimilation. Some studies have demonstrated the intrinsic relation between miRNAs and their targets, and how they can modulate plants to deal with the NPK availability. In this review, we focus on miRNAs and their regulation of targets involved in NPK metabolism. In general, NPK starvation is related with miRNAs that are involved in root architectural changes and uptake activity modulation. We further show that several miRNAs were discovered to be involved in plant-microbe symbiosis during N and P uptake, and in this way we present a global view of some studies that were conducted in the last years. The integration of current knowledge about miRNA-NPK signaling may help future studies to focus in good candidates genes for the development of important tools for plant nutritional breeding. PMID- 26136765 TI - Promoting flowering, lateral shoot outgrowth, leaf development, and flower abscission in tobacco plants overexpressing cotton FLOWERING LOCUS T (FT)-like gene GhFT1. AB - FLOWERING LOCUS T (FT) encodes a mobile signal protein, recognized as major component of florigen, which has a central position in regulating flowering, and also plays important roles in various physiological aspects. A mode is recently emerging for the balance of indeterminate and determinate growth, which is controlled by the ratio of FT-like and TERMINAL FLOWER 1 (TFL1)-like gene activities, and has a strong influence on the floral transition and plant architecture. Orthologs of GhFT1 was previously isolated and characterized from Gossypium hirsutum. We demonstrated that ectopic overexpression of GhFT1 in tobacco, other than promoting flowering, promoted lateral shoot outgrowth at the base, induced more axillary bud at the axillae of rosette leaves, altered leaf morphology, increased chlorophyll content, had higher rate of photosynthesis and caused flowers abscission. Analysis of gene expression suggested that flower identity genes were significantly upregulated in transgenic plants. Further analysis of tobacco FT paralogs indicated that NtFT4, acting as flower inducer, was upregulated, whereas NtFT2 and NtFT3 as flower inhibitors were upregulated in transgenic plants under long-day conditions, but downregulated under short-day conditions. Our data suggests that sufficient level of transgenic cotton FT might disturb the balance of the endogenous tobacco FT paralogs of inducers and repressors and resulted in altered phenotype in transgenic tobacco, emphasizing the expanding roles of FT in regulating shoot architecture by advancing determine growth. Manipulating the ratio for indeterminate and determinate growth factors throughout FT-like and TFL1-like gene activity holds promise to improve plant architecture and enhance crop yield. PMID- 26136766 TI - Evidence for an intrinsic factor promoting landscape genetic divergence in Madagascan leaf-litter frogs. AB - The endemic Malagasy frog radiations are an ideal model system to study patterns and processes of speciation in amphibians. Large-scale diversity patterns of these frogs, together with other endemic animal radiations, led to the postulation of new and the application of known hypotheses of species diversification causing diversity patterns in this biodiversity hotspot. Both extrinsic and intrinsic factors have been studied in a comparative framework, with extrinsic factors usually being related to the physical environment (landscape, climate, river catchments, mountain chains), and intrinsic factors being clade-specific traits or constraints (reproduction, ecology, morphology, physiology). Despite some general patterns emerging from such large-scale comparative analyses, it became clear that the mechanism of diversification in Madagascar may vary among clades, and may be a multifactorial process. In this contribution, I test for intrinsic factors promoting population-level divergence within a clade of terrestrial, diurnal leaf-litter frogs (genus Gephyromantis) that has previously been shown to diversify according to extrinsic factors. Landscape genetic analyses of the microendemic species Gephyromantis enki and its widely distributed, larger sister species Gephyromantis boulengeri over a rugged landscape in the Ranomafana area shows that genetic variance of the smaller species cannot be explained by landscape resistance alone. Both topographic and riverine barriers are found to be important in generating this divergence. This case study yields additional evidence for the probable importance of body size in lineage diversification. PMID- 26136767 TI - Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+. AB - Mutations in C19orf12 have been identified in patients affected by Neurodegeneration with Brain Iron Accumulation (NBIA), a clinical entity characterized by iron accumulation in the basal ganglia. By using western blot analysis with specific antibody and confocal studies, we showed that wild-type C19orf12 protein was not exclusively present in mitochondria, but also in the Endoplasmic Reticulum (ER) and MAM (Mitochondria Associated Membrane), while mutant C19orf12 variants presented a different localization. Moreover, after induction of oxidative stress, a GFP-tagged C19orf12 wild-type protein was able to relocate to the cytosol. On the contrary, mutant isoforms were not able to respond to oxidative stress. High mitochondrial calcium concentration and increased H2O2 induced apoptosis were found in fibroblasts derived from one patient as compared to controls. C19orf12 protein is a 17 kDa mitochondrial membrane-associated protein whose function is still unknown. Our in silico investigation suggests that, the glycine zipper motifs of C19orf12 form helical regions spanning the membrane. The N- and C-terminal regions with respect to the transmembrane portion, on the contrary, are predicted to rearrange in a structural domain, which is homologs to the N-terminal regulatory domain of the magnesium transporter MgtE, suggesting that C19orf12 may act as a regulatory protein for human MgtE transporters. The mutations here described affect respectively one glycine residue of the glycine zipper motifs, which are involved in dimerization of transmembrane helices and predicted to impair the correct localization of the protein into the membranes, and one residue present in the regulatory domain, which is important for protein-protein interaction. PMID- 26136768 TI - Long non-coding RNA SOX2OT: expression signature, splicing patterns, and emerging roles in pluripotency and tumorigenesis. AB - SOX2 overlapping transcript (SOX2OT) is a long non-coding RNA which harbors one of the major regulators of pluripotency, SOX2 gene, in its intronic region. SOX2OT gene is mapped to human chromosome 3q26.3 (Chr3q26.3) locus and is extended in a high conserved region of over 700 kb. Little is known about the exact role of SOX2OT; however, recent studies have demonstrated a positive role for it in transcription regulation of SOX2 gene. Similar to SOX2, SOX2OT is highly expressed in embryonic stem cells and down-regulated upon the induction of differentiation. SOX2OT is dynamically regulated during the embryogenesis of vertebrates, and delimited to the brain in adult mice and human. Recently, the disregulation of SOX2OT expression and its concomitant expression with SOX2 have become highlighted in some somatic cancers including esophageal squamous cell carcinoma, lung squamous cell carcinoma, and breast cancer. Interestingly, SOX2OT is differentially spliced into multiple mRNA-like transcripts in stem and cancer cells. In this review, we are describing the structural and functional features of SOX2OT, with an emphasis on its expression signature, its splicing patterns and its critical function in the regulation of SOX2 expression during development and tumorigenesis. PMID- 26136770 TI - The aging-disease false dichotomy: understanding senescence as pathology. AB - From a biological perspective aging (senescence) appears to be a form of complex disease syndrome, though this is not the traditional view. This essay aims to foster a realistic understanding of aging by scrutinizing ideas old and new. The conceptual division between aging-related diseases and an underlying, non pathological aging process underpins various erroneous traditional ideas about aging. Among biogerontologists, another likely error involves the aspiration to treat the entire aging process, which recent advances suggest is somewhat utopian. It also risks neglecting a more modest but realizable goal: to develop preventative treatments that partially protect against aging. PMID- 26136769 TI - Replication of Structured DNA and its implication in epigenetic stability. AB - DNA replication is an extremely risky process that cells have to endure in order to correctly duplicate and segregate their genome. This task is particularly sensitive to DNA damage and multiple mechanisms have evolved to protect DNA replication as a block to the replication fork could lead to genomic instability and possibly cell death. The DNA in the genome folds, for the most part, into the canonical B-form but in some instances can form complex secondary structures such as G-quadruplexes (G4). These G rich regions are thermodynamically stable and can constitute an obstacle to DNA and RNA metabolism. The human genome contains more than 350,000 sequences potentially capable to form G-quadruplexes and these structures are involved in a variety of cellular processes such as initiation of DNA replication, telomere maintenance and control of gene expression. Only recently, we started to understand how G4 DNA poses a problem to DNA replication and how its successful bypass requires the coordinated activity of ssDNA binding proteins, helicases and specialized DNA polymerases. Their role in the resolution and replication of structured DNA crucially prevents both genetic and epigenetic instability across the genome. PMID- 26136771 TI - Clinical applications of next generation sequencing in cancer: from panels, to exomes, to genomes. AB - This article will review recent impact of massively parallel next-generation sequencing (NGS) in our understanding and treatment of cancer. While whole exome sequencing (WES) remains popular and effective as a method of genetically profiling different cancers, advances in sequencing technology has enabled an increasing number of whole-genome based studies. Clinically, NGS has been used or is being developed for genetic screening, diagnostics, and clinical assessment. Though challenges remain, clinicians are in the early stages of using genetic data to make treatment decisions for cancer patients. As the integration of NGS in the study and treatment of cancer continues to mature, we believe that the field of cancer genomics will need to move toward more complete 100% genome sequencing. Current technologies and methods are largely limited to coding regions of the genome. A number of recent studies have demonstrated that mutations in non-coding regions may have direct tumorigenic effects or lead to genetic instability. Non-coding regions represent an important frontier in cancer genomics. PMID- 26136772 TI - Challenging the anthropocentric emphasis on phenotypic testing in prokaryotic species descriptions: rip it up and start again. PMID- 26136773 TI - Epidemiological characterization and prognostic factors in patients with confirmed cerebral cryptococcosis in central Taiwan. AB - BACKGROUND: Cryptococcal meningitis is a deadly fungal infection. This study aimed to characterize the epidemiology of cerebral cryptococcosis and to define its prognostic factors. METHODS: This cross-sectional study collected clinical information from cryptococcal meningitis patients with confirmed cerebral cryptococcosis from 2006 to 2012 at the Changhua Christian Healthcare System to access prognostic factors. RESULTS: Fifty-nine adult cryptococcal meningitis patients were studied. The incidence at Changhua Christian Healthcare System was approximately 170 episodes per 100,000 patients within the studied period. Forty one of 59 cryptococcal meningitis patients developed complications. Overall, 12 of 59 patients died, for a three-month mortality rate of 20.3 %. Prognostic factors positively associated with the three-month mortality included age (>55 years), patient delay, prolonged delay by the doctor in administering antifungal agent therapy, duration of intensive care unit stay, chronic lung disease, cryptococcemia, headache, altered mental status, positive blood cultures, and high cerebrospinal fluid opening pressure (>=250 mm H2O). CONCLUSIONS: We strongly recommend early administration of an antifungal agent to each suspected cryptococcal meningitis patient to decrease both the delay by doctors in administering therapy and the mortality risk. Aggressive and supportive care for severe cryptococcal meningitis patients is critical to decrease overall mortality from this infection. PMID- 26136774 TI - Automated Feature Extraction in Brain Tumor by Magnetic Resonance Imaging Using Gaussian Mixture Models. AB - This paper presents a novel method for Glioblastoma (GBM) feature extraction based on Gaussian mixture model (GMM) features using MRI. We addressed the task of the new features to identify GBM using T1 and T2 weighted images (T1-WI, T2 WI) and Fluid-Attenuated Inversion Recovery (FLAIR) MR images. A pathologic area was detected using multithresholding segmentation with morphological operations of MR images. Multiclassifier techniques were considered to evaluate the performance of the feature based scheme in terms of its capability to discriminate GBM and normal tissue. GMM features demonstrated the best performance by the comparative study using principal component analysis (PCA) and wavelet based features. For the T1-WI, the accuracy performance was 97.05% (AUC = 92.73%) with 0.00% missed detection and 2.95% false alarm. In the T2-WI, the same accuracy (97.05%, AUC = 91.70%) value was achieved with 2.95% missed detection and 0.00% false alarm. In FLAIR mode the accuracy decreased to 94.11% (AUC = 95.85%) with 0.00% missed detection and 5.89% false alarm. These experimental results are promising to enhance the characteristics of heterogeneity and hence early treatment of GBM. PMID- 26136775 TI - Diagnostic Accuracy of 256-Detector Row Computed Tomography in Detection and Characterization of Incidental Pancreatic Cystic Lesions. AB - Purpose. To assess the diagnostic value of 256-detector row MDCT in the characterization of incidentally detected pancreatic cystic lesions (PCLs). Materials and Methods. We retrospectively reviewed 6389 studies performed on a 256-row detector scanner, wherein >=1 PCLs were incidentally detected. Images from a total of 192 patients (99 females; age range 31-90 years) were analysed referring to morphologic predictive signs of malignancy, including multifocality, inner septa, wall thickening, and mural enhancing nodules. Results. We evaluated 292 PCLs in 192 patients (solitary in 145 and >=2 in 47; incidence 2.05%). Size ranged from 3 to 145 mm (mean 15 mm); body was the most common location (87/292; 29.8%). Intralesional septa were detected in 52/292 lesions (17.8%), wall thickening >2 mm in 13 (4.5%), enhancing wall and mural nodules in 15 (5.1%) and 12 (4.1%), respectively. Communication with ductal system was evident in 45 cases. The most common diagnoses, established by histology or imaging analysis, were IPMNs (about 86%), while serous cystic neoplasia (3.7%) and metastases (0.5%) were the less common. Conclusion. MDCT provides detailed features for characterization of PCLs, which are incidentally discovered with increased frequency due to the widespread use of cross-sectional imaging. PMID- 26136776 TI - Nephroprotective Potential of Human Albumin Infusion: A Narrative Review. AB - Albumin infusion improves renal function in cirrhosis; however, mechanisms are incompletely understood. In clinical practice, human albumin is used in various intensive care unit indications to deal with a wide range of problems, from volume replacement in hypovolemic shock, or sepsis, to treatment of ascites in patients with liver cirrhosis. Against the background of the results of recent studies on the use of human albumin in septic patients, the importance of the natural colloid in these critically ill patients is being redefined. In addition to the hemodynamic effects of administration of human albumin impacting on sympathetic tone, attention is being paid to other effects in which its pharmacodynamics is associated with the physiological importance of endogenous albumin. The morbidity and mortality data discussed in this paper support the importance of both the hemodynamic and the pharmacological effects of the administration of human albumin in various indications. The contribution that human albumin could make towards the maintenance of renal function in the course and treatment of severe sepsis and cirrhosis of the liver is the subject of this narrative review. PMID- 26136777 TI - Depth of Anesthesia as a Risk Factor for Perioperative Morbidity. AB - Introduction. The prognostic value of age, physical status, and duration of surgery on perioperative course has been extensively studied. However, the impact of deep hypnotic time (time when Bispectral Index values are less than 40) has not been well evaluated. Methods. We designed an observational study to clarify the relative influence of deep hypnotic time (DHT) on outcome. Eligible participants were mentally stable patients over 18 years old scheduled for elective major abdominal surgery. In total, 248 patients enrolled. Data were analyzed using Fisher's exact test and multiple logistic regression. Results. Five variables (DHT, hypotension, age, comorbidity, and duration of surgery) showed statistically significant association with complications, when examined independently. However, when all variables were examined together in a multiple logistic regression model, age and comorbidity were no longer associated with outcome. DHT, hypotension, and duration of surgery were significant predictors of "complications," and "hypotension" was a significant predictor of prolonged hospital stay (P < 0.001). Conclusion. Deep hypnotic time emerged as a new factor associated with outcome, and its impact compared to other factors such as age, surgery duration, hypotension, and comorbidity is redefined. Monitoring and managing depth of anesthesia during surgery are important and should be part of careful operation planning. PMID- 26136778 TI - Changes in Serum TSH and T4 Levels after Switching the Levothyroxine Administration Time from before Breakfast to before Dinner. AB - Background. Levothyroxine is commonly used in the treatment of patients with hypothyroidism. Levothyroxine is most often administered in the morning, on an empty stomach, in order to increase its oral absorption. However, many patients have difficulties taking levothyroxine in the morning. Aim. The aim of this study was evaluating the effect of changing levothyroxine administration time from before breakfast to before dinner on the serum levels of TSH and T4. Subjects and Methods. Fifty patients between 18 and 75 years old with hypothyroidism were included in the study and were randomly divided into two groups. Each group received two tablets per day (one levothyroxine tablet and one placebo tablet) 30 minutes before breakfast and 1 hour before dinner. After two months, the administration time for the tablets was changed for each group, and the new schedule was continued for a further two-month period. The serum TSH and T4 levels were measured before and after treatment in each group. Results. Changing the levothyroxine administration time resulted in 1.47 +/- 0.51 uIU/mL increase in TSH level (p = 0.001) and 0.35 +/- 1.05 ug/dL decrease in T4 level (p = 0.3). Conclusions. Changing the levothyroxine administration time from before breakfast to before dinner reduced the therapeutic efficacy of levothyroxine. PMID- 26136780 TI - The Prevalence and Associated Risk Factors of Impaired Glucose Regulation in Chinese Adults: A Population-Based Cross-Sectional Study. AB - The goal of this study was to determine the prevalence and associated risk factors of impaired glucose regulation (IGR) in the population of Tongzhou, China, and to provide scientific basis for preventive interventions. In the study, the overall age-standardized prevalence of IGR (16.0%) in Tongzhou residents was higher than that in the national population (15.0%). There was no significant geographic difference in prevalence of IGR between urban and rural males. Older age, elevated blood pressure, high serum lipids, overweight, and central obesity were significantly associated with increased risk of IGR. PMID- 26136781 TI - Regulation of Cardiovascular Metabolism by Hormones and Growth Factors. PMID- 26136779 TI - Mechanisms Linking Inflammation to Insulin Resistance. AB - Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuation of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance. In this paper, we discuss how these factors and signaling pathways contribute to insulin resistance and the therapeutic promise targeting inflammation in insulin resistance based on the latest experimental studies. PMID- 26136782 TI - Corrigendum to "Determination of Oxidative Stress Related Toxicity on Repeated Dermal Exposure of Hydroxyapatite Nanoparticles in Rats". AB - [This corrects the article DOI: 10.1155/2014/476942.]. PMID- 26136783 TI - Progressive Familial Intrahepatic Cholestasis: A Rare Cause of Cirrhosis in Young Adult Patients. AB - Hepatic cirrhosis is an important cause of morbidity and mortality. An unusual case of cirrhosis and portal hypertension in an 18-year-old patient secondary to Progressive Intrahepatic Cholestasis is discussed. The clinical and biochemical findings are discussed and a clinical approach to determining the underlying etiology of cirrhosis is outlined. Significant complications of portal hypertension include ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, varices, and hepatic encephalopathy. A clinical approach to these complications of cirrhosis is presented. Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare congenital metabolic abnormality. There are 3 subtypes and Type 3 PFIC commonly presents in late adolescence and early adulthood. Clinical and laboratory findings as well as management for the condition are described. PMID- 26136784 TI - EGFR Amplification and Glioblastoma Stem-Like Cells. AB - Glioblastoma (GBM), the most common malignant brain tumor in adults, contains a subpopulation of cells with a stem-like phenotype (GS-cells). GS-cells can be maintained in vitro using serum-free medium supplemented with epidermal growth factor, basic fibroblast growth factor-2, and heparin. However, this method does not conserve amplification of the Epidermal Growth Factor Receptor (EGFR) gene, which is present in over 50% of all newly diagnosed GBM cases. GS-cells with retained EGFR amplification could overcome the limitations of current in vitro model systems and contribute significantly to preclinical research on EGFR targeted therapy. This review recapitulates recent methodological approaches to expand stem-like cells from GBM with different EGFR status in order to maintain EGFR-dependent intratumoral heterogeneity in vitro. Further, it will summarize the current knowledge about the impact of EGFR amplification and overexpression on the stem-like phenotype of GBM-derived GS-cells and different approaches to target the EGFR-dependent GS-cell compartment of GBM. PMID- 26136786 TI - Corrigendum to "High Dose Dexmedetomidine: Effective as a Sole Agent Sedation for Children Undergoing MRI". AB - [This corrects the article DOI: 10.1155/2015/397372.]. PMID- 26136785 TI - Human Umbilical Cord Mesenchymal Stem Cells: A New Therapeutic Option for Tooth Regeneration. AB - Tooth regeneration is considered to be an optimistic approach to replace current treatments for tooth loss. It is important to determine the most suitable seed cells for tooth regeneration. Recently, human umbilical cord mesenchymal stem cells (hUCMSCs) have been regarded as a promising candidate for tissue regeneration. However, it has not been reported whether hUCMSCs can be employed in tooth regeneration. Here, we report that hUCMSCs can be induced into odontoblast-like cells in vitro and in vivo. Induced hUCMSCs expressed dentin related proteins including dentin sialoprotein (DSP) and dentin matrix protein-1 (DMP-1), and their gene expression levels were similar to those in native pulp tissue cells. Moreover, DSP- and DMP-1-positive calcifications were observed after implantation of hUCMSCs in vivo. These findings reveal that hUCMSCs have an odontogenic differentiation potency to differentiate to odontoblast-like cells with characteristic deposition of dentin-like matrix in vivo. This study clearly demonstrates hUCMSCs as an alternative therapeutic cell source for tooth regeneration. PMID- 26136788 TI - From the Editor-in-Chief. PMID- 26136787 TI - High Risk Infants Follow-Up: A Case Study in Iran. AB - Background. A follow-up program for high risk infants was initiated in Alzahra Maternity Hospital in Tabriz city, Iran, in 2013. The aim of this paper is to give a brief report of the program. Material and Methods. Two groups of high risk neonates were studied. The first group comprising 509 infants received services in Alzahra Maternity Hospital implemented by the follow-up program. This included a full package for family to look after high risk infant and periodic clinical evaluation at two and four weeks after birth and then two, three, four, five, and six months later again. The second group including 131 infants in Taleqani Maternity Hospital received routine services after birth with no specific follow up care. Results. Some anthropometric indices showed a significant improvement in the intervention hospital compared to control group. These included the following: head circumference at first and second months; weight in the first, fourth, fifth, and sixth months; and height in sixth month only. Clinical evaluation of infants showed an improvement for some of the medical conditions. Conclusion. Follow-up care program for a minimum of six months after discharge from maternity hospitals may help to avoid adverse and life threatening consequences in high risk infants. PMID- 26136789 TI - Preliminary results of an early vs delayed timing of surgery in the management of proximal femur fragility fractures. AB - INTRODUCTION: The appropriate surgical timing for the treatment of proximal femur fractures is still debated. Advantages of a delayed surgery may be: stabilization of systemic diseases, decrease of the risk of perioperative mortality and morbidity. An early timing of surgery may allow: early mobilization, reduction of the risks of disability and hospital stays, early return to home of the patients. However, the effects on mortality are still discussed. PURPOSE: The purpose of this study is to assess the influence of the surgical timing on clinical outcomes, complications, and mortality in a preliminary experience of the early management of these fractures vs the delayed surgery. METHODS: A series of 176 patients was retrospectively evaluated. 132 patients were followed-up for one year after surgery. The evaluation was performed by the assessment of the comorbidities, preoperative wait for surgery, type of fracture and procedures, hospital stay, and functional outcomes: 33 patients were operated with an early timing, 99 with a delayed surgery. RESULTS: The mean mortality rate was 18.2% in the early timing (6/33 patients), and 23.2% in the delayed timing (23/99 patients): no significant difference was recorded in the preliminary analysis. Postoperative complications were recorded in 28 patients (21.2%): 4 patients were operated within 48 hours (12.1%) and 24 after 48 hours (24.2%) with no substantial differences. The postoperative hospital stay showed no correlation with the timing of surgery, as no evidence was found on the functional recovery and postoperative disability. CONCLUSIONS: No significant differences were found on the evaluated parameters in the two groups in the present preliminary study. A correlation between male sex and mortality, and male sex and postoperative complications was assessed. An enlargement of the study population is needed to surely clarify any effective differences, given the fact that recent studies seem to identify in the early treatment the better strategy to ensure the best recovery and the lower rate of mortality and complications. PMID- 26136790 TI - Copper, magnesium, zinc and calcium status in osteopenic and osteoporotic post menopausal women. AB - Copper, magnesium, zinc and calcium status were measured in postmenopausal women with osteoporosis (n = 23) and osteopenia (n = 28) as classified on the basis of the T-score of the femur neck and dual energy X-ray absorptiometry results. Anthropometric indices, dietary intake and serum copper, magnesium, zinc and calcium were assessed. The results of our study showed that the mean dietary intake of magnesium, zinc and calcium in post-menopausal women with low bone density were significantly lower than recommended dietary allowance. The mean serum levels of zinc (P = 0.001) and copper (P = 0.000) were significantly lower than normal range and 40.4% of this participants had serum magnesium levels lower than normal range. No statistically significant differences were observed between the osteopenic and osteoporotic groups with respect to serum levels and dietary intakes of copper, calcium, magnesium and zinc. Due to the mineral deficiency in post-menopausal women with low bone density and the key role of minerals on bone health, supplementation with magnesium, calcium, zinc and perhaps copper recommended. PMID- 26136792 TI - Algodystrophy: recent insight into the pathogenic framework. AB - Algodystrophy, nowadays called CRPS I, is a painful syndrome characterized by sensory and vasomotor disturbance, edema and functional impairment. Significant progress in knowledge about the pathogenic mechanisms of the disease have been recently achieved, but they are not yet fully understood and some clinical aspects are still lacking of a whole pathogenetic comprehension. The local release of pro-inflammatory neuropeptides and some cytokines may be the event that triggers and maintains the disease, causing hyperalgesia and allodynia. In the following phases, the impaired capillary permeability, the interstitial edema and the consequent hypoxia and local acidosis have been proposed as possible pathophysiological pathways. The local hyperactivity of the sympathetic nervous system supposed in the past has not be confirmed and the hypothesis of an altered nociceptive processing at CNS level has limited evidences in acute phases of the disease. The steady bone involvement could be confirmed by the efficacy of bisphosphonates in the treatment of early disease. PMID- 26136793 TI - Effectiveness and utility of hyaluronic acid in osteoarthritis. AB - Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and progressive functional limitation. Viscosupplementation with intra-articular hyaluronic acid is a treatment option in knee OA that is included in the professional guidelines for treatment of this joint disease, but potentially should apply to all synovial joints in order to reduce pain and improve joint lubrication. Exogenous HA can enhance chondrocyte HA synthesis, prevent the degradation of cartilage and promote its regeneration. Moreover it can reduce the production of proinflammatory mediators and matrix metalloproteinases involved in OA pathogenesis. This mini review highlights the evidence of hyaluronic acid in reducing osteoarthritis symptoms and structural damage, as well as its ability to delay prosthetic surgery. Viscosupplementation should be considered as a long term therapy. PMID- 26136791 TI - The pathogenetic bases of sarcopenia. AB - Aging is accompanied by involuntary loss of skeletal muscle mass, strength and function, called sarcopenia. The mechanisms underlying the development of sarcopenia are not completely understood and most likely multi-factorial, but significant progress has been made over the past few years to identify some of the major contributors. Besides life style-related factors, as diet and physical activity, sarcopenia seems to be also determined by hormonal dysregulation, chronic inflammatory status, ectopic adipose tissue accumulation, neurological and vascular changes associated with aging. The present mini-review focused on the basic factors that primarily impact muscle homeostasis in older subjects. A better understanding of cellular mechanism leading to sarcopenia is required to establish evidence-based intervention in order to prevent onset of symptoms associated with sarcopenia and to extend the time free from disability in older adults. PMID- 26136794 TI - The T.A.R.Ge.T. project: a regional program to reduce hip fracture in elderly patients. Main results of retrospective phase. AB - The Tuscany Region was the first Italian Region to initiate a program for the prevention of hip fractures in over 65 year old. The T.A.R.Ge.T. project "Appropriate treatment of geriatric re-fractures in Tuscany" (Trattamento Appropriato delle Rifratture Geriatriche in Toscana), which is still on-going, includes a preliminary phase (2009-2010) for baseline analysis and education of the participating centers and a 4-year-prospective phase (2011-2014). The monitoring system is performed horizontally analyzing 5 different flows: SDO (Performance Hospitalization), SPF (Pharmaceutical Distribution Dataset), FED (Direct Distribution Dataset), SAA (Registry of Patients), SPA (Specialized Outpatient) flows. In this review will be shown some of the most important results of analyzes of the retrospective phase. Between 2006 and 2011 only 26% of hip fractured patients has being treated with anti-osteoporotic drugs. The percentage of treatment increases 10% after the second fracture. Until 2011 there wasn't in Tuscany a prevention program of bone fragility; patients were treated with specific treatment only in severe cases: this phenomenon implies that mortality and re-fracture are higher on treated patients than in patients who did not have any kind of treatment. The treated patients are the most severe and therefore they have a higher risk of death and re-fracture. PMID- 26136795 TI - Bone care nurses and the evolution of the nurse's educational function: the Guardian Angel((r)) research project. AB - Osteoporosis mostly affects females over 50 years old, worldwide. The main osteoporosis complication is fragility fractures that reduce quality of life and cause morbidity and mortality. Most patients who have fragility fractures are treated for the fracture. However, patients' adherence to follow-up treatment plans is poor. Therefore, tailored educational interventions are needed to improve medication adherence and healthy lifestyles. In this context, the role of bone care nurses is important, as they can act at different levels of osteoporosis prevention and fracture liaison services, which are secondary fracture prevention programmes implemented by health care systems to treat osteoporotic patients. In Italy, a research project called Guardian Angel((r)) was developed to provide tailored education to osteoporotic women in order to improve their disease management and reduce related complications. PMID- 26136796 TI - Pre-operative diclofenac HPbetaCD for pain control of needle biopsy in musculoskeletal neoplasm: preliminary results. AB - Needle biopsy is the main standard method used for diagnosis of musculoskeletal tumors of the limbs and superficial trunk. Pain control during this procedure is through the use of Local Anaestetic (L.A.). In order to achieve a complete pain control in our cases, recently we started using diclofenac HPbetaCD 50 mg via s.c. preoperativly. We present the clinical results of a non-randomized study of two eterogeneous groups of patients: "Experimental" Group (1): diclofenac HPbetaCD 50 mg via s.c. one hour before surgical procedure, local anesthesia and ev. diclofenac HPbetaCD 50 mg via s.c. 12 hours postoperative; "Conventional" Group (2): local anesthesia and ev. postoperative tramadol 100 mg via oral for pain control. In October 2014, at the Department of Orthopedic Oncology and Reconstructive Surgery of Florence, 37 musculoskeletal biopsies for a bone or a soft tissue lesion were performed. Exclusion criteria for this study were: known allergies to lidocaine, diclofenac, tramadol; known gastric or duodenal ulcers; known gastrointestinal bleed or perforation; refusal of the patients to collaborate. For one or more of these reasons, 6 patients were excluded from this study. In the Group 1, 10 patients (59%) referred no pain during the surgical procedure (8/14 biopsies on soft tissue and 2/3 on bone). In 5 cases (29%) no exacerbation of previous chronic pain, and in 2 cases (12%) a progression of local pain after biopsy (average 1 points higher in the VAS). In Group 2, only 6 patients (42%) did not have any pain during the procedure, 4 (29%) no exacerbation of previous chronic pain and 4 (29%) a progression of local pain (average 2 points higher in the VAS). Despite similar results in both Groups, Group 1 seemed to have a mild better control of perioperative pain. The use of diclofenac HPbetaCD 50 mg preoperative seems to be a rational approach for minimizing perioperative pain and the preliminary data of our study seem encouraging. Obviously many bias are present in this study (small numbers of cases, heterogeneity of diseases, association with local anesthetic, non randomized study, comparison between preoperative versus postoperative treatment) and this cannot absolutely be considerate as definitive conclusions. PMID- 26136797 TI - Osteoid producing primary lesion at morphologic and biologic interface. AB - Fibroosseous gnathic lesions comprise a wide spectrum of diseases. Many of the entities have overlapping features. A pediatric case is encountered with a complex clinicopathologic profile. Although radiographically the lesion appears benign but on histopathological examination it possesses features of osteoid producing aggressive neoplasm. This paper highlights the unusual histologic features existing within the spectrum of fibroosseous lesions and discusses relevant clinicopathologic correlations. PMID- 26136798 TI - Stemless humeral component in reverse shoulder prosthesis in patient with Parkinson's disease: a case report. AB - INTRODUCTION: In patients with Parkinson's disease falling is very common and for this reason, the prosthetic surgical indication in shoulder is reserved for special cases. PD has been linked to several interrelated factors that may contribute to failure of shoulder arthroplasty. CASE PRESENTATION: A 65-year-old woman with PD, severe pain, recurrent bursitis, swelling and functional limitation to all movements in left shoulder presented to our attention. Radiographic and CT exams show cuff-tear arthropathy. The patient was submitted to implantation of a Reverse Shoulder Comprehensive Nano cementless modular system (Biomet((r)), Warsaw, IN, USA) with anterosuperior surgical approach. We chose this kind of solution of stemless humeral component after bone mineral consideration. DISCUSSION: Reverse shoulder arthroplasty represents an option in the management of glenohumeral arthritis. Poor functional results of RTSA in patients with PD have been attributed to increased muscle tone, severity of tremor and an increased mortality rate. In general, post operative complications related to the humeral component are dominated by fractures (between 1 and 3%): in patients with PD this percentage is higher because of falls often occur. With a stemless implant revisions can be performed easily. Overall, the anterosuperior surgical exposure gives a low risk of postoperative instability. CONCLUSION: In selected cases of patients with PD, after carefully analysis of bone quality, the use of a stemless component is of benefit in the possible revision cases for periprosthetic fractures and the use of an anterosuperior exposure reduces the percentage of instability. The results obtained about the pain relief are excellent in contrast with functional outcomes that remain poor. PMID- 26136799 TI - Tendoachillis avulsion in osteomalacia. AB - Sixteen-year-old girl presented with generalized body pain with avulsion of tendoachillis on minimal trauma. Surgical repair led to complete recovery. Investigations revealed severe osteomalacia, which improved on supplementation. Surgical difficulty encountered was soft nature of bone, difficult attachment of tendon and delayed rehabilitation. Vitamin D evaluation is essential in young females presenting with generalized body pain and pain at attachments of strong muscles with bones. PMID- 26136800 TI - A rare case report of tumoral calcinosis syndrome in an adult with rheumatoid arthritis. AB - Tumoral calcinosis is a rare benign disease entity that mimics a neoplasm and is manifested by calcium deposition in the soft tissues around the large joints. It can be primary or secondary to renal failure and hyperparathyroidism. This is, to our knowledge, the first reported case of tumoral calcinosis in a Hispanic male with rheumatoid arthritis. PMID- 26136801 TI - A case of oncogenic osteomalacia due to occult nasal sinus tumor. AB - This paper shows a case of oncogenic osteomalacia in a 35-year-old man who presented with a 2-year history of generalized pain and progressive weakness of lower limbs, eventually became bed bound. At admission he had severe hip pain resulting from atraumatic femoral neck fractures. Laboratory investigations revealed hypophosphatemia, hyperphosphaturia, normocalcemia, elevated alkaline phosphatase, and normal serum levels of parathormone and 25-hydroxyvitamin D. Serum FGF-23 was elevated. Imaging showed osteoporosis and insufficiency fractures of the femoral neck. Whole body functional imaging failed to reveal any areas of increased activity. However, on computed tomography (CT) and magnetic resonance (MR) imaging, a tumor was discovered at left nasal cavity. The patient was treated with phosphate supplements and vitamin D, but his hypophosphatemia persisted. The tumor was surgically removed. Histologically, the tumor was diagnosed as variant of a sinonasal hemangiopericytoma-like tumor. After surgery, his symptoms were relieved and biochemical parameters normalized. PMID- 26136803 TI - Unilateral compressive optic neuropathy due to skull hyperostosis secondary to nutritional vitamin A deficiency. AB - We report a 17-year-old boy who presented with a chronic left unilateral optic neuropathy. Computerized tomography and magnetic resonance imaging demonstrated compression of the left optic nerve due to skull hyperostosis. He was found to be profoundly vitamin A deficient secondary to an unusual diet consisting predominantly of potato chips and crisps. Skull hyperostosis with cranial neuropathies and other neurological abnormalities has been described in growing animals fed vitamin A deficient diets but has not been previously reported in humans. PMID- 26136802 TI - Severe polyarthritis secondary to zolendronic acid: a case report and literature review. AB - Intravenous zolendronic acid is an established anti-resorptive treatment for post menopausal osteoporosis and is usually well tolerated. Common side effects, including the classical 'acute phase response', are consented for prior to treatment. However, rare but serious adverse reactions to zolendronic acid have been described. We report the case of an older patient with osteoporosis and osteoarthritis who presented within 12 hours of her first zolendronic acid infusion with evidence of a severe acute polyarthritis affecting her peripheral appendicular skeleton, in joints affected by pre-existing osteoarthritis. Despite the prevalence of osteoarthritis, this is the most severe case of polyarthritis following intravenous zolendronic acid to date and only the second reported case. We remind prescribing physicians treating patients with intravenous bisphosphonates, to bear in mind possible rare serious adverse reactions as well as common benign side effects. We postulate age-associated frailty may reduce tolerability to even milder acute phase reactions. PMID- 26136804 TI - Voriconazole-related periostitis presenting on magnetic resonance imaging. AB - Painful periostitis is a complication of long-term antifungal therapy with voriconazole. A high clinical suspicion coupled with imaging and laboratory assessment is useful to establish the diagnosis. Prompt discontinuance of voriconazole typically results in the resolution of symptoms and signs. This report describes the presentation of voriconazole-related periostitis on magnetic resonance imaging. PMID- 26136805 TI - Can injection of PMMA-microspheres cause hypercalcemia? PMID- 26136806 TI - Healing Relationships: A Qualitative Study of Healers and Their Clients in Germany. AB - Background. The aim of this study was to investigate the nature of the relationships between healers and their clients in Germany. Methods. An interdisciplinary research team performed semistructured interviews with healers and clients and participatory observation of healing sessions. All interviews were digitally recorded, transcribed, and analyzed using content analysis. Results. Fifteen healers and sixteen clients were included. The healer-client relationship was described as a profound and unique experience, which brought forth interpersonal and spiritual connections. The healers were seen as role models for healing to occur and support for being connected spiritually. The clients had to be open-minded and responsible. The importance of the healers' empathy was emphasized. Discussion. The relationship between healer and client can be seen as a triangular connection between client, healer, and a transcendent source which is not the case in typical patient-doctor relationships. The spiritual connection is also said to enhance the empathetic understanding of the healer. The personality and a partner-like attitude of the healer supported the client in giving a more positive meaning to his life, in reconnecting to his spirituality, and in taking responsibility. Future studies should address the role of spirituality in health care and the development of enduring healer-client relationships. PMID- 26136807 TI - Loving-Kindness Meditation to Target Affect in Mood Disorders: A Proof-of-Concept Study. AB - Conventional treatments for mood disorders primarily focus on reducing negative affect, but little on enhancing positive affect. Loving-kindness meditation (LKM) is a traditional meditation practice directly oriented toward enhancing unconditional and positive emotional states of kindness towards oneself and others. We report here two independent and uncontrolled studies carried out at different centers, one in Boston, USA (n = 10), and one in Frankfurt, Germany (n = 8), to examine the potential therapeutic utility of a brief LKM group intervention for symptoms of dysthymia and depression. Results at both centers suggest that LKM was associated with large-sized effects on self-reported symptoms of depression (d = 3.33 and 1.90), negative affect (d = 1.98 and 0.92), and positive affect (d = 1.63 and 0.94). Large effects were also found for clinician-reported changes in depression, rumination and specific positive emotions, and moderate effects for changes in adaptive emotion regulation strategies. The qualitative data analyses provide additional support for the potential clinical utility of the intervention. This proof-of-concept evaluation of LKM as a clinical strategy warrants further investigation. PMID- 26136808 TI - Simplified Tai Chi Resistance Training versus Traditional Tai Chi in Slowing Bone Loss in Postmenopausal Women. AB - Background. This study examined whether simplified Tai Chi resistance training is superior to traditional Tai Chi in slowing bone loss in postmenopausal women. Methods. This prospective trial included 119 postmenopausal women (age: 52-65 years). Subjects were randomly assigned to participate in a traditional Tai Chi program (TTC, n = 40), a simplified Tai Chi resistance training program (TCRT, n = 40), or a blank control group (routine activity, n = 39). The TTC involved traditional Yang Style Tai Chi. The primary outcome was the change of lumbar bone mass density (L2-L4) at 12 months over the baseline. Femoral neck and Ward's triangle were also measured using dual-energy X-ray absorptiometry. Results. The L2-L4 density was significantly lower at 12 months in comparison to the baseline in the blank control group. In both the TCRT and TTC groups, the L2-L4 density was comparable to the baseline. There was a trend for less bone loss in the TCRT than in the TTC group. Similar findings were observed with femoral neck and Ward's triangle. Conclusion. Simplified Tai Chi resistance training could slow bone loss in menopausal women. The results also suggested, but did not confirm, superiority to traditional Tai Chi. PMID- 26136809 TI - Potent Antiproliferative Effect on Liver Cancer of Medicinal Plants Selected from the Thai/Lanna Medicinal Plant Recipe Database "MANOSROI III". AB - Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including liver cancer. In this study, methanolic extracts (MEs) of 23 plants were tested for antiproliferative activity on human hepatoma cell line (Hep G2) by the sulforhodamine B (SRB) assay. Nine MEs with potent antiproliferative activity (IC50 < 100 ug/mL) were obtained and further semipurified by liquid/liquid partition extraction. The semipurified fractions were tested for the antiproliferative and antioxidative activities. ME of Stemona collinsae and the semipurified extract and methanol-water fraction (MF) of Gloriosa superba gave the highest antiproliferative activity on HepG2 which were 4.79- and 50.07-fold cisplatin, respectively. The semipurified fractions showed an increased antiproliferative activity. MF of Caesalpinia sappan and HF of Senna alata showed the highest free radical scavenging and metal chelating activities, respectively. The compound in n-hexane fraction (HF) of Ventilago denticulata which showed an increase in antiproliferative activity comparing to its ME was isolated and identified as emodin. This study has demonstrated the potential of the ME from S. collinsae, MF from G. superba, and emodin isolated from V. denticulata, for further development as an antiliver cancer agent. PMID- 26136810 TI - Thermoregulatory Responses to Graded Exercise Differ among Sasang Types. AB - We compared sweat rate and variables such as workload (W e ), metabolic heat production (H prod), and temperature increment load (T inc) across Sasang types. 304 apparently healthy participants aged 20-49 years with their Sasang type determined were enrolled. Local sweat rates on the chest (LSRchest) and back (LSRback) were measured using a perspiration meter during a maximum treadmill exercise test. Oxygen uptake was measured continuously using a breath-by-breath mode indirect calorimeter. The TaeEum (TE) type had a larger body size, a higher percent body fat, and a lower body area surface area (BSA) to body mass compared with the other Sasang types, particularly the SoEum (SE) type. The TE type tended to have a shorter exercise time to exhaustion and lower maximal oxygen uptake (mL.kg(-1).min(-1)) than the other types. LSRchest in TE types was greater than that of the SE and SoYang (SY) types in men, whereas LSRback was higher in the TE type than that of the other types in women. After normalizing LSR for W e , H prod, T inc, and BSA, this tendency still remained. Our findings suggest that the thermoregulatory response to graded exercise may differ across Sasang types such that the TE type was the most susceptible to heat stress. PMID- 26136811 TI - A Good Policy for Guaranteed Safe Practice of Complementary and Alternative Medicine, Usage of Disposable Cupping Cups. PMID- 26136813 TI - Automatic Evaluation of Voice Quality Using Text-Based Laryngograph Measurements and Prosodic Analysis. AB - Due to low intra- and interrater reliability, perceptual voice evaluation should be supported by objective, automatic methods. In this study, text-based, computer aided prosodic analysis and measurements of connected speech were combined in order to model perceptual evaluation of the German Roughness-Breathiness Hoarseness (RBH) scheme. 58 connected speech samples (43 women and 15 men; 48.7 +/- 17.8 years) containing the German version of the text "The North Wind and the Sun" were evaluated perceptually by 19 speech and voice therapy students according to the RBH scale. For the human-machine correlation, Support Vector Regression with measurements of the vocal fold cycle irregularities (CFx) and the closed phases of vocal fold vibration (CQx) of the Laryngograph and 33 features from a prosodic analysis module were used to model the listeners' ratings. The best human-machine results for roughness were obtained from a combination of six prosodic features and CFx (r = 0.71, rho = 0.57). These correlations were approximately the same as the interrater agreement among human raters (r = 0.65, rho = 0.61). CQx was one of the substantial features of the hoarseness model. For hoarseness and breathiness, the human-machine agreement was substantially lower. Nevertheless, the automatic analysis method can serve as the basis for a meaningful objective support for perceptual analysis. PMID- 26136812 TI - Monte Carlo Calculation of Radioimmunotherapy with (90)Y-, (177)Lu-, (131)I-, (124)I-, and (188)Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts. AB - Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like (131)I or (90)Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of (90)Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as (90)Y, (177)Lu, (131)I, (124)I, and (188)Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). (90)Y and (188)Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases. PMID- 26136814 TI - Analytical comparison study of the clinical and radiological outcome of spine fixation using posterolateral, posterior lumber interbody and transforaminal lumber interbody spinal fixation techniques to treat lumber spine degenerative disc disease. AB - BACKGROUND: Degenerative disc disease is a common cause of chronic and disabling back pain that requires surgical intervention, posterolateral and posterior instrumental fixation (PLF), posterior lumber interbody fusion (PLIF) and transforaminal lumber interbody fusion (TLIF) are the techniques used to deal with such a problem. OBJECTIVE: To compare the clinical and radiological outcome of the variable surgical techniques used to deal with Lumber degenerative disc disease and to recommend the technique of choice. METHODS: 120 patients were treated between 2003 and 2010 at king Abdullah university hospital for lumber disc disease. The patients were divided into three groups: Group I (PLF n = 30 [59 levels]); Group II (PLIF n = 40 [70 levels]); and Group III (TLIF n = 50 [96 levels]). All patients had the same pre- and postoperative clinical and radiological evaluations (using Stanford score and local criteria and Oswestry Disability Index [ODI],). All cases had three months and then yearly for five years follow ups. RESULTS: There was no observed difference in the rates of intra operative complications (Group I: 10 %; Group II: 8 %; Group III: 14 %; p = 0.566) and postoperative complications (Group I: 13.3 %, Group II:17.5 %, Group III: 18 % with p = 0.332). Among the groups. There was a vital decrease in the ODI scores over time (p < 0.005) but no major difference among the groups at different follow-up times. Radiographic fusion rates for Groups I, II and III were 90 %, 92.5 % and 94 %, respectively. CONCLUSIONS: The surgical outcome of PLF, PLIF and TLIF used to treat degenerative disc disease is almost similar, there is no significant differences observed in complications and clinical outcomes. However, TILF may have better radiological outcome. PMID- 26136815 TI - Detecting conserved protein complexes using a dividing-and-matching algorithm and unequally lenient criteria for network comparison. AB - The increase of protein-protein interaction (PPI) data of different species makes it possible to identify common subnetworks (conserved protein complexes) across species via local alignment of their PPI networks, which benefits us to study biological evolution. Local alignment algorithms compare PPI network of different species at both protein sequence and network structure levels. For computational and biological reasons, it is hard to find common subnetworks with strict similar topology from two input PPI networks. Consequently some methods introduce less strict criteria for topological similarity. However those methods fail to consider the differences of the two input networks and adopt equally lenient criteria on them. In this work, a new dividing-and-matching-based method, namely UEDAMAlign is proposed to detect conserved protein complexes. This method firstly uses known protein complexes or computational methods to divide one of the two input PPI networks into subnetworks and then maps the proteins in these subnetworks to the other PPI network to get their homologous proteins. After that, UEDAMAlign conducts unequally lenient criteria on the two input networks to find common connected components from the proteins in the subnetworks and their homologous proteins in the other network. We carry out network alignments between S. cerevisiae and D. melanogaster, H. sapiens and D. melanogaster, respectively. Comparisons are made between other six existing methods and UEDAMAlign. The experimental results show that UEDAMAlign outperforms other existing methods in recovering conserved protein complexes that both match well with known protein complexes and have similar functions. PMID- 26136816 TI - Microbial colonization of open abdomen in critically ill surgical patients. AB - INTRODUCTION: This study was designed to describe the time-course and microbiology of colonization of open abdomen in critically ill surgical patients and to study its association with morbidity, mortality and specific complications of open abdomen. A retrospective cohort analysis was done. METHODS: One hundred eleven consecutive patients undergoing vacuum-assisted closure with mesh as temporary abdominal closure method for open abdomen were analyzed. Microbiological samples from the open abdomen were collected. Statistical analyses were performed using Fisher's exact test for categorical variables. Mann Whitney U test was used when comparing number of temporary abdominal closure changes between colonized and sterile patients. Kaplan-Meier analysis was done to calculate cumulative estimates for colonization. Cox regression analyses were performed to analyze risk factors for colonization. RESULTS: Microbiological samples were obtained from 97 patients. Of these 76 (78 %) were positive. Sixty one (80 %) patients were colonized with multiple micro-organisms and 27 (36 %) were cultured positive for candida species. The duration of open abdomen treatment adversely affected the colonization rate. Thirty-three (34 %) patients were colonized at the time of laparostomy. After one week of open abdomen treatment 69, and after two weeks 76 patients were colonized with cumulative colonization estimates of 74 % and 89 %, respectively. Primary fascial closure rate was 80 % (61/76) and 86 % (18/21) for the colonized and sterile patients, respectively. The rate of wound complications did not significantly differ between these groups. CONCLUSIONS: Microbial colonization of open abdomen is associated with the duration of open abdomen treatment. Wound complications are common after open abdomen, but colonization does not seem to have significant effect on these. The high colonization rate described herein should be taken into account when primarily sterile conditions like acute pancreatitis and aortic aneurysmal rupture are treated with open abdomen. PMID- 26136817 TI - One year experience of swine dermal non-crosslinked collagen prostheses for abdominal wall repairs in elective and emergency surgery. AB - INTRODUCTION: The approach to the abdominal wall surgical repair is dramatically changed in the last years. This study evaluates our institutional outcomes about the usage of biological meshes for abdominal wall repair in different setting: in elective surgery, in emergency surgery and in abdominal wall repair following open abdomen (OA) procedure. METHODS: A database was prospectively conducted (January-December 2014) and data were reviewed for patients who underwent to an abdominal wall reconstruction with swine dermal non-cross linked collagens prostheses either in elective or emergency setting, and following OA/laparostomy procedure. Demographic data, co-morbidities, indications for surgery, intra operative details, post-operative complications and outcome (peri-operative, 3, 6, 9-months) were analyzed. RESULTS: A total of 30 cases were reported: 9 in elective surgery (Group 1), 4 in emergency surgery (Group 2) and 17 with abdominal wall closure following OA management (Group 3). Two meshes were removed: 1 in the Group 1 and 1 in the Group 3. During follow-up only one patient in the Group 3 had a recurrence of the incisional hernia. Mortality rate was 11.1 % at 3 months in Group 1, 0 % in the Group 2, and 29.4 % in peri-operative period in the Group 3. CONCLUSIONS: The use of non-cross linked biological meshes can be safe and versatile in different situations from elective to emergency surgery, and also for the reconstruction of the abdominal wall after OA procedure, with an acceptable recurrence and mortality rate. PMID- 26136818 TI - Research highlights for issue 6: the CRISPR/Cas revolution. PMID- 26136820 TI - Evolutionary perspective of cancer: myth, metaphors, and reality. AB - The evolutionary perspective of cancer (which origins and dynamics result from evolutionary processes) has gained significant international recognition over the past decade and generated a wave of enthusiasm among researchers. In this context, several authors proposed that insights into evolutionary and adaptation dynamics of cancers can be gained by studying the evolutionary strategies of organisms. Although this reasoning is fundamentally correct, in our opinion, it contains a potential risk of excessive adaptationism, potentially leading to the suggestion of complex adaptations that are unlikely to evolve among cancerous cells. For example, the ability of recognizing related conspecifics and adjusting accordingly behaviors as in certain free-living species appears unlikely in cancer. Indeed, despite their rapid evolutionary rate, malignant cells are under selective pressures for their altered lifestyle for only few decades. In addition, even though cancer cells can theoretically display highly sophisticated adaptive responses, it would be crucial to determine the frequency of their occurrence in patients with cancer, before therapeutic applications can be considered. Scientists who try to explain oncogenesis will need in the future to critically evaluate the metaphorical comparison of selective processes affecting cancerous cells with those affecting organisms. This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications. PMID- 26136819 TI - Cancer: an emergent property of disturbed resource-rich environments? Ecology meets personalized medicine. AB - For an increasing number of biologists, cancer is viewed as a dynamic system governed by evolutionary and ecological principles. Throughout most of human history, cancer was an uncommon cause of death and it is generally accepted that common components of modern culture, including increased physiological stresses and caloric intake, favor cancer development. However, the precise mechanisms for this linkage are not well understood. Here, we examine the roles of ecological and physiological disturbances and resource availability on the emergence of cancer in multicellular organisms. We argue that proliferation of 'profiteering phenotypes' is often an emergent property of disturbed, resource-rich environments at all scales of biological organization. We review the evidence for this phenomenon, explore it within the context of malignancy, and discuss how this ecological framework may offer a theoretical background for novel strategies of cancer prevention. This work provides a compelling argument that the traditional separation between medicine and evolutionary ecology remains a fundamental limitation that needs to be overcome if complex processes, such as oncogenesis, are to be completely understood. PMID- 26136821 TI - Spatiotemporal dynamics of Puumala hantavirus associated with its rodent host, Myodes glareolus. AB - Many viruses significantly impact human and animal health. Understanding the population dynamics of these viruses and their hosts can provide important insights for epidemiology and virus evolution. Puumala virus (PUUV) is a European hantavirus that may cause regional outbreaks of hemorrhagic fever with renal syndrome in humans. Here, we analyzed the spatiotemporal dynamics of PUUV circulating in local populations of its rodent reservoir host, the bank vole (Myodes glareolus) during eight years. Phylogenetic and population genetic analyses of all three genome segments of PUUV showed strong geographical structuring at a very local scale. There was a high temporal turnover of virus strains in the local bank vole populations, but several virus strains persisted through multiple years. Phylodynamic analyses showed no significant changes in the local effective population sizes of PUUV, although vole numbers and virus prevalence fluctuated widely. Microsatellite data demonstrated also a temporally persisting subdivision between local vole populations, but these groups did not correspond to the subdivision in the virus strains. We conclude that restricted transmission between vole populations and genetic drift play important roles in shaping the genetic structure and temporal dynamics of PUUV in its natural host which has several implications for zoonotic risks of the human population. PMID- 26136822 TI - Linking genetic and environmental factors in amphibian disease risk. AB - A central question in evolutionary biology is how interactions between organisms and the environment shape genetic differentiation. The pathogen Batrachochytrium dendrobatidis (Bd) has caused variable population declines in the lowland leopard frog (Lithobates yavapaiensis); thus, disease has potentially shaped, or been shaped by, host genetic diversity. Environmental factors can also influence both amphibian immunity and Bd virulence, confounding our ability to assess the genetic effects on disease dynamics. Here, we used genetics, pathogen dynamics, and environmental data to characterize L. yavapaiensis populations, estimate migration, and determine relative contributions of genetic and environmental factors in predicting Bd dynamics. We found that the two uninfected populations belonged to a single genetic deme, whereas each infected population was genetically unique. We detected an outlier locus that deviated from neutral expectations and was significantly correlated with mortality within populations. Across populations, only environmental variables predicted infection intensity, whereas environment and genetics predicted infection prevalence, and genetic diversity alone predicted mortality. At one locality with geothermally elevated water temperatures, migration estimates revealed source-sink dynamics that have likely prevented local adaptation. We conclude that integrating genetic and environmental variation among populations provides a better understanding of Bd spatial epidemiology, generating more effective conservation management strategies for mitigating amphibian declines. PMID- 26136823 TI - Human mining activity across the ages determines the genetic structure of modern brown trout (Salmo trutta L.) populations. AB - Humans have exploited the earth's metal resources for thousands of years leaving behind a legacy of toxic metal contamination and poor water quality. The southwest of England provides a well-defined example, with a rich history of metal mining dating to the Bronze Age. Mine water washout continues to negatively impact water quality across the region where brown trout (Salmo trutta L.) populations exist in both metal-impacted and relatively clean rivers. We used microsatellites to assess the genetic impact of mining practices on trout populations in this region. Our analyses demonstrated that metal-impacted trout populations have low genetic diversity and have experienced severe population declines. Metal-river trout populations are genetically distinct from clean-river populations, and also from one another, despite being geographically proximate. Using approximate Bayesian computation (ABC), we dated the origins of these genetic patterns to periods of intensive mining activity. The historical split of contemporary metal-impacted populations from clean-river fish dated to the Medieval period. Moreover, we observed two distinct genetic populations of trout within a single catchment and dated their divergence to the Industrial Revolution. Our investigation thus provides an evaluation of contemporary population genetics in showing how human-altered landscapes can change the genetic makeup of a species. PMID- 26136824 TI - The contribution of phenotypic plasticity to the evolution of insecticide tolerance in amphibian populations. AB - Understanding population responses to rapid environmental changes caused by anthropogenic activities, such as pesticides, is a research frontier. Genetic assimilation (GA), a process initiated by phenotypic plasticity, is one mechanism potentially influencing evolutionary responses to novel environments. While theoretical and laboratory research suggests that GA has the potential to influence evolutionary trajectories, few studies have assessed its role in the evolution of wild populations experiencing novel environments. Using the insecticide, carbaryl, and 15 wood frog populations distributed across an agricultural gradient, we tested whether GA contributed to the evolution of pesticide tolerance. First, we investigated the evidence for evolved tolerance to carbaryl and discovered that population-level patterns of tolerance were consistent with evolutionary responses to pesticides; wood frog populations living closer to agriculture were more tolerant than populations living far from agriculture. Next, we tested the potential role of GA in the evolution of pesticide tolerance by assessing whether patterns of tolerance were consistent with theoretical predictions. We found that populations close to agriculture displayed constitutive tolerance to carbaryl whereas populations far from agriculture had low naive tolerance but high magnitudes of induced tolerance. These results suggest GA could play a role in evolutionary responses to novel environments in nature. PMID- 26136825 TI - The evolutionary legacy of size-selective harvesting extends from genes to populations. AB - Size-selective harvesting is assumed to alter life histories of exploited fish populations, thereby negatively affecting population productivity, recovery, and yield. However, demonstrating that fisheries-induced phenotypic changes in the wild are at least partly genetically determined has proved notoriously difficult. Moreover, the population-level consequences of fisheries-induced evolution are still being controversially discussed. Using an experimental approach, we found that five generations of size-selective harvesting altered the life histories and behavior, but not the metabolic rate, of wild-origin zebrafish (Danio rerio). Fish adapted to high positively size selective fishing pressure invested more in reproduction, reached a smaller adult body size, and were less explorative and bold. Phenotypic changes seemed subtle but were accompanied by genetic changes in functional loci. Thus, our results provided unambiguous evidence for rapid, harvest-induced phenotypic and evolutionary change when harvesting is intensive and size selective. According to a life-history model, the observed life-history changes elevated population growth rate in harvested conditions, but slowed population recovery under a simulated moratorium. Hence, the evolutionary legacy of size-selective harvesting includes populations that are productive under exploited conditions, but selectively disadvantaged to cope with natural selection pressures that often favor large body size. PMID- 26136826 TI - Consequences of extensive habitat fragmentation in landscape-level patterns of genetic diversity and structure in the Mediterranean esparto grasshopper. AB - Anthropogenic habitat fragmentation has altered the distribution and population sizes in many organisms worldwide. For this reason, understanding the demographic and genetic consequences of this process is necessary to predict the fate of populations and establish management practices aimed to ensure their viability. In this study, we analyse whether the spatial configuration of remnant semi natural habitat patches within a chronically fragmented landscape has shaped the patterns of genetic diversity and structure in the habitat-specialist esparto grasshopper (Ramburiella hispanica). In particular, we predict that agricultural lands constitute barriers to gene flow and hypothesize that fragmentation has restricted interpopulation dispersal and reduced local levels of genetic diversity. Our results confirmed the expectation that isolation and habitat fragmentation have reduced the genetic diversity of local populations. Landscape genetic analyses based on circuit theory showed that agricultural land offers ?1000 times more resistance to gene flow than semi-natural habitats, indicating that patterns of dispersal are constrained by the spatial configuration of remnant patches of suitable habitat. Overall, this study shows that semi-natural habitat patches act as corridors for interpopulation gene flow and should be preserved due to the disproportionately large ecological function that they provide considering their insignificant area within these human-modified landscapes. PMID- 26136828 TI - Substrate specificity and regioselectivity of fungal AA9 lytic polysaccharide monooxygenases secreted by Podospora anserina. AB - BACKGROUND: The understanding of enzymatic polysaccharide degradation has progressed intensely in the past few years with the identification of a new class of fungal-secreted enzymes, the lytic polysaccharide monooxygenases (LPMOs) that enhance cellulose conversion. In the fungal kingdom, saprotrophic fungi display a high number of genes encoding LPMOs from family AA9 but the functional relevance of this redundancy is not fully understood. RESULTS: In this study, we investigated a set of AA9 LPMOs identified in the secretomes of the coprophilous ascomycete Podospora anserina, a biomass degrader of recalcitrant substrates. Their activity was assayed on cellulose in synergy with the cellobiose dehydrogenase from the same organism. We showed that the total release of oxidized oligosaccharides from cellulose was higher for PaLPMO9A, PaLPMO9E, and PaLPMO9H that harbored a carbohydrate-binding module from the family CBM1. Investigation of their regioselective mode of action revealed that PaLPMO9A and PaLPMO9H oxidatively cleaved at both C1 and C4 positions while PaLPMO9E released only C1-oxidized products. Rapid cleavage of cellulose was observed using PaLPMO9H that was the most versatile in terms of substrate specificity as it also displayed activity on cello-oligosaccharides and beta-(1,4)-linked hemicellulose polysaccharides (e.g., xyloglucan, glucomannan). CONCLUSIONS: This study provides insights into the mode of cleavage and substrate specificities of fungal AA9 LPMOs that will facilitate their application for the development of future biorefineries. PMID- 26136829 TI - Development of a stress-induced mutagenesis module for autonomous adaptive evolution of Escherichia coli to improve its stress tolerance. AB - BACKGROUND: Microbial tolerance to different environmental stresses is of importance for efficient production of biofuels and biochemical. Such traits are often improved by evolutionary engineering approaches including mutagen-induced mutagenesis and successive passage. In contrast to these approaches which generate mutations in rapidly growing cells, recent research showed that mutations could be generated in non-dividing cells under stressful but non-lethal conditions, leading to the birth of the theory of stress-induced mutagenesis (SIM). A molecular mechanism of SIM has been elucidated to be mutagenic repair of DNA breaks. This inspired us to develop a synthetic SIM module to simulate the mutagenic cellular response so as to accelerate microbial adaptive evolution for an improved stress tolerance. RESULTS: A controllable SIM evolution module was devised based on a genetic toggle switch in Escherichia coli. The synthetic module enables expression and repression of the genes related to up- and down regulation responses during SIM in a bistable way. Upon addition of different inducers, the module can be turned on or off, triggering transition to a mutagenic or a high-fidelity state and thus allowing periodic adaptive evolution. Six genes (recA, dinB, umuD, ropS, ropE, and nusA) in the up-regulation responses were evaluated for their potentials to enhance the SIM rate. Expression of recA, dinB, or ropS alone increased the SIM rate by 4.5- to 13.7-fold, whereas their combined expression improved the rate by 31.9-fold. Besides, deletion of mutL increased the SIM rate by 82-fold. Assembly of these genes into the SIM module in the mutL-deletion E. coli strain elevated the SIM rate by nearly 3000-fold. Accelerated adaptive evolution of E. coli equipped with this synthetic SIM module was demonstrated under n-butanol stress, with the minimal inhibitory concentration of n-butanol increasing by 56 % within 2.5 months. CONCLUSIONS: A synthetic SIM module was constructed to simulate cellular mutagenic responses during SIM. Based on this, a novel evolutionary engineering approach-SIM-based adaptive evolution-was developed to improve the n-butanol tolerance of E. coli. PMID- 26136830 TI - Digital mobile technology facilitates HIPAA-sensitive perioperative messaging, improves physician-patient communication, and streamlines patient care. AB - BACKGROUND: Mobile device technology has revolutionized interpersonal communication, but the application of this technology to the physician-patient relationship remains limited due to concerns over patient confidentiality and the security of digital information. Nevertheless, there is a continued focus on improving communication between doctors and patients in all fields of medicine as a means of improving patient care. In this study, we implement a novel communications platform to demonstrate that instantaneously sharing perioperative information with surgical patients and members of their support networks can improve patient care and strengthen the physician-patient relationship. METHODS: 423 consecutive patients scheduled to undergo elective surgical procedures were offered complimentary registration to a secure, web-based service designed to distribute perioperative updates to a group of recipients designated by each patient via Short Message Service (SMS) and/or email. Messages were created by attending surgeons and delivered instantaneously through the web-based platform. In the postoperative period, patients and their designated message recipients, as well as participating healthcare providers, were asked to complete a survey designed to assess their experience with the messaging system. Survey results were statistically analyzed to determine satisfaction rates. RESULTS: Of the qualifying 423 patients, 313 opted to enroll in the study. On average, patients selected a total of 3.5 recipients to receive perioperative updates. A total of 1,195 electronic messages were generated for distribution to designated recipients during the study period and delivered to recipients located around the world. There were no documented errors or failures in message delivery. Satisfaction surveys were completed by 190 users of the service (73 %). Respondents identified themselves as either patients (n = 48, 25.5 %), family/friends (n = 120, 63.8 %), or healthcare providers (n = 15, 12 %). Satisfaction with the service was high: 94.2 % of users "enjoyed this software" and and 94.2 % of family/friends "felt more connected to their loved ones during surgery." 92.5 % would "recommend their loved ones sign up for this service". Ninety percent of patients who completed the survey reported "an improved hospital experience". CONCLUSION: Digital communications platforms can facilitate the immediate transfer of HIPAA-compliant data to patients and their designees. Such systems can greatly improve the level of communication between physicians, patients, and patients' families and caregivers. All types of users, including healthcare professionals, patients, and their loved ones, recorded high levels of satisfaction. Based on these observations, we conclude that mobile digital communications platforms represent a way to harness the power of social media to enhance patient care. PMID- 26136831 TI - Cost-effectiveness Assessment of Cardiac Interventions: Determining a Socially Acceptable Cost Threshold. AB - Health care is a vital good for which there is an infinite demand. However, societal resources are finite and need to be distributed efficiently to avoid waste. Thus, the relative value of an intervention - cost compared to its effectiveness- needs to be taken into consideration when deciding which interventions to adopt. Cost-effectiveness analysis provides the crucial information which guides these decisions. As the field of medicine and indeed cardiology move forward with innovations which are effective but often expensive, it becomes imperative to employ these cost-effectiveness analytic tools, not with the intention of denying vital health services but to ascertain what the society willing to pay for. PMID- 26136832 TI - High rates of submicroscopic aberrations in karyotypically normal acute lymphoblastic leukemia. AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) is not a single uniform disease. It consists of several subgroups with different cytogenetic and molecular genetic aberrations, clinical presentations and outcomes. Banding cytogenetics plays a pivotal role in the detection of recurrent chromosomal rearrangements and is the starting point of genetic analysis in ALL, still. Nowadays, molecular (cyto)genetic tools provide substantially to identify previously non-detectable, so-called cryptic chromosomal aberrations in ALL. However, ALL according to banding cytogenetics with normal karyotype - in short cytogenetically normal ALL (CN-ALL) - represent up to ~50 % of all new diagnosed ALL cases. The overall goal of this study was to identify and characterize the rate of cryptic alterations in CN-ALL and to rule out if one single routine approach may be sufficient to detect most of the cryptic alterations present. RESULTS: Sixty-one ALL patients with CN ALL were introduced in this study. All of them underwent high resolution fluorescence in situ hybridization (FISH) analysis. Also DNA could be extracted from 34 ALL samples. These DNA-samples were studied using a commercially available MLPA (multiplex ligation-dependent probe amplification) probe set directed against 37 loci in hematological malignancies and/or array-comparative genomic hybridization (aCGH). Chromosomal aberrations were detected in 21 of 61 samples (~34 %) applying FISH approaches: structural abnormalities were present in 15 cases and even numerical ones were identified in 6 cases. Applying molecular approaches copy number alterations (CNAs) were detected in 27/34 samples. Overall, 126 CNAs were identified and only 34 of them were detectable by MLPA (~27 %). Loss of CNs was identified in ~80 % while gain of CNs was present in ~20 % of the 126 CNAs. A maximum of 13 aberrations was detected per case; however, only one aberration per case was found in 8 of all in detail studied 34 cases. Of special interest among the detected CNAs are the following new findings: del(15)(q26.1q26.1) including CHD2 gene was found in 20 % of the studied ALL cases, dup(18)(q21.2q21.2) with the DCC gene was present in 9 % of the cases, and the CDK6 gene in 7q21.2 was deleted in 12 % of the here in detail studied ALL cases. CONCLUSIONS: In conclusion, high resolution molecular cytogenetic tools and molecular approaches like MLPA and aCGH need to be combined in a cost-efficient way, to identify disease and progression causing alterations in ALL, as majority of them are cryptic in banding cytogenetic analyses. PMID- 26136833 TI - Assessment of copy number variations in the brain genome of schizophrenia patients. AB - BACKGROUND: Cytogenomic mutations and chromosomal abnormality are implicated in the neuropathology of several brain diseases. Cell heterogeneity of brain tissues makes their detection and validation difficult, however. In the present study, we analyzed gene dosage alterations in brain DNA of schizophrenia patients and compared those with the copy number variations (CNVs) identified in schizophrenia patients as well as with those in Asian lymphocyte DNA and attempted to obtain hints at the pathological contribution of cytogenomic instability to schizophrenia. RESULTS: Brain DNA was extracted from postmortem striatum of schizophrenia patients and control subjects (n = 48 each) and subjected to the direct two color microarray analysis that limits technical data variations. Disease-associated biases of relative DNA doses were statistically analyzed with Bonferroni's compensation on the premise of brain cell mosaicism. We found that the relative gene dosage of 85 regions significantly varied among a million of probe sites. In the candidate CNV regions, 26 regions had no overlaps with the common CNVs found in Asian populations and included the genes (i.e., ANTXRL, CHST9, DNM3, NDST3, SDK1, STRC, SKY) that are associated with schizophrenia and/or other psychiatric diseases. The majority of these candidate CNVs exhibited high statistical probabilities but their signal differences in gene dosage were less than 1.5-fold. For test evaluation, we rather selected the 10 candidate CNV regions that exhibited higher aberration scores or larger global effects and were thus confirmable by PCR. Quantitative PCR verified the loss of gene dosage at two loci (1p36.21 and 1p13.3) and confirmed the global variation of the copy number distributions at two loci (11p15.4 and 13q21.1), both indicating the utility of the present strategy. These test loci, however, exhibited the same somatic CNV patterns in the other brain region. CONCLUSIONS: The present study lists the candidate regions potentially representing cytogenomic CNVs in the brain of schizophrenia patients, although the significant but modest alterations in their brain genome doses largely remain to be characterized further. PMID- 26136834 TI - Specialized enteral nutrition therapy in Crohn's disease patients on maintenance infliximab therapy: a meta-analysis. AB - OBJECTIVES: Many patients with Crohn's disease on infliximab maintenance therapy have recurrent symptoms despite an initial clinical response. Therefore, concomitant therapies have been studied. We conducted a meta-analysis to assess the effect of specialized enteral nutrition therapy with infliximab versus infliximab monotherapy in patients with Crohn's disease. METHODS: A comprehensive search of multiple databases was performed. All studies of adult patients with Crohn's disease comparing specialized enteral nutrition therapy (elemental or polymeric diet with low-fat or regular diet) with infliximab versus infliximab monotherapy without dietary restrictions were included. Meta-analysis was performed using the Mantel-Haenszel (fixed effect) model with odds ratio (OR) to assess for clinical remission. RESULTS: Four studies (n = 342) met inclusion criteria. Specialized enteral nutrition therapy with infliximab resulted in 109 of 157 (69.4%) patients reaching clinical remission compared with 84 of 185 (45.4%) with infliximab monotherapy [OR 2.73; 95% confidence interval (CI): 1.73 4.31, p < 0.01]. Similarly, 79 of 106 (74.5%) patients receiving enteral nutrition therapy and infliximab remained in clinical remission after one year compared with 62 of 126 (49.2%) patients receiving infliximab monotherapy (OR 2.93; 95% CI: 1.66-5.17, p < 0.01). No publication bias or heterogeneity was noted for either outcome. CONCLUSIONS: The use of specialized enteral nutrition therapy in combination with infliximab appears to be more effective at inducing and maintaining clinical remission among patients with Crohn's disease than infliximab monotherapy. PMID- 26136835 TI - Endoscopic management of iatrogenic perforations during endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for colorectal polyps: a case series. AB - BACKGROUND: Iatrogenic perforation during therapeutic colonoscopy, reported in up to 1% of endoscopic mucosal resections (EMRs) and up to 14% of endoscopic submucosal dissections (ESDs), has conventionally been an indication for surgery. AIMS: We present a case series of successful endoscopic management of iatrogenic colorectal perforation during EMR and ESD, demonstrating the feasibility and safety of the method. METHODS: Retrospective analysis of a database of patients undergoing EMR and ESD for colorectal polyps in a tertiary referral centre in the United Kingdom. RESULTS: Four cases of perforation were identified (two EMRs and two ESDs) in a series of 218 procedures (1.8%), all detected at the time of endoscopy and managed with endoscopic clips. Patients were observed in hospital and treated with antibiotics. Their median length of stay was 3 days (range 2-6 days), with no mortality or need for surgery. CONCLUSION: Surgery is no longer the first choice in the management of iatrogenic perforations during EMR and ESD for colorectal polyps; in selected patients with small perforations and minimal extraluminal contamination, conservative management with application of endoscopic clips, antibiotics and close patient monitoring constitute a safe and effective treatment option, avoiding the morbidity of major surgery. PMID- 26136836 TI - Endoscopic closure of persistent gastrocutaneous fistulae, after percutaneous endoscopic gastrostomy (PEG) tube placement, using the over-the-scope-clip system. AB - OBJECTIVES: The Over-The-Scope-Clip (OTSC) has had an evolving role in endoscopic closure of gastrointestinal wall defects, in hemostasis of primary or postinterventional bleeding, and approximation of postbariatric surgery defects. Rapid and effective closure of gastrocutaneous (GC) fistulae using this device has been recently described in the literature. The aim of this study was to evaluate the technical feasibility, efficacy and safety of OTSC as an effective tool in the management of persistent GC fistulae secondary to a complication of percutaneous endoscopic gastrostomy (PEG) tube placement. METHOD: In this multicenter prospective observational study, we describe our experience with OTSC in the closure of persistent GC fistulas secondary to PEG tube placement. Patients with GC fistulas were sequentially enrolled with a mean age of 84 years. Primary treatment outcome was the immediate successful closure of GC fistula and resolution of leak. Secondary outcome was no recurrence of the fistula and leaks on follow up. RESULTS: A total of 10 patients were enrolled over the study period. Mean age was 84.4 +/- 8.75 years. The primary treatment outcome was achieved in all the patients undergoing this intervention. Secondary outcome was observed in 9/10 (90%) subjects. No procedural complications were reported. Larger fistulae (>2.5 cm) and those with significant fibrosis were more difficult to close with the OTSC system. The mean follow-up time after OTSC application was 43.7 +/- 20.57 days. A limitation of this study was that there was no control group. CONCLUSIONS: OTSC application is a safe and effective endoscopic approach for the closure of persistent GC fistulae secondary to a complication of PEG tube placement. PMID- 26136837 TI - Docetaxel and its potential in the treatment of refractory esophagogastric adenocarcinoma. AB - Adenocarcinomas of the esophagus and stomach are a major cause of cancer-related morbidity and mortality worldwide. For patients with advanced disease, first-line chemotherapy with platinum-fluoropyrimidine combinations prolongs survival, but inevitably the disease progresses with a median progression-free survival of approximately 6 months. At the time of progression, approximately 40-50% of patients remain fit and eligible for second-line treatment. Docetaxel has been extensively studied in this chemorefractory setting, mostly in small single arm studies, either as a single agent or in combination with platinum agents, fluoropyrimidines or anthracyclines. However, two randomized controlled trials published since 2012 have convincingly shown that treatment with docetaxel modestly prolongs survival compared with best supportive care alone. Moreover, treatment with docetaxel is associated with relief from cancer-related constitutional and gastrointestinal symptoms with manageable, predominantly haematological, toxicity. Therefore, it represents a valuable treatment option for patients with relapsed esophagogastric cancer. Nevertheless, in view of the short survival time for the majority of these patients, further research is necessary to identify, on the one hand, combinations with targeted agents that will further improve outcomes and, on the other, biomarkers that will allow selection of those patients most likely to benefit. PMID- 26136838 TI - Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities. AB - With the recent introduction and approval of medications directed at the treatment of opioid induced constipation (OIC) in patients with nonmalignant pain, there is increased interest and understanding of the unmet need and opportunities to enhance patient management. The high incidence of OIC is associated with rapid increase of narcotic analgesic prescriptions for nonmalignant chronic pain. This review addresses briefly the mechanisms of action of opioids that lead to OIC, the differential tolerance of gastrointestinal organs to the effects of opioids, the size and scope of the problem, the definition and outcome measures for OIC, current differential diagnosis and management algorithms, and the pharmacology and efficacy of treatments for OIC in patients with nonmalignant pain. PMID- 26136840 TI - Conservative management of esophageal perforation due to external air-blast injury: a case report and literature review. PMID- 26136839 TI - Choosing the optimal method in programmatic colorectal cancer screening: current evidence and controversies. AB - Colorectal cancer (CRC) is an important health problem all over the world, being the third most common cancer and the second leading cause of cancer-related death in Western countries. The most important strategy for CRC prevention is screening (i.e. secondary prevention). Since it is widely accepted that adenomas and serrated polyps are the precursors of the vast majority of CRC, early detection and removal of these lesions is associated with a reduction of CRC incidence and, consequently, mortality. Moreover, cancers detected by screening are usually diagnosed at early stages and, therefore, curable by endoscopic or surgical procedures. This review will be address CRC screening strategies in average-risk population, which is defined by those individuals, men and women, 50 years of age or older, without any additional personal or familial predisposing risk factor. In order to maximize the impact of screening and ensure high coverage and equity of access, only organized screening programs (i.e. programmatic screening) should be implemented, as opposed to case-finding or opportunistic screening. For that reason and considering that the optimal approach for colorectal screening may differ depending on the scenario, this review will be focused on the advantages and limitations of each screening strategy in an organized setting. PMID- 26136841 TI - Endoscopic closure of gastrocutaneous fistula with an AMPLATZER(TM) septal occluder device. PMID- 26136842 TI - Subcutaneous immunoglobulin in treating inflammatory neuromuscular disorders. AB - OBJECTIVE: Intravenous immunoglobulin administration has long been used in the treatment of autoimmune neuromuscular disorders. Immunoglobulins may be administered by intramuscular, intravenous or subcutaneous routes. METHODS: This is a report on the long-term clinical follow up of six patients with inflammatory neuromuscular disorders, that is, three chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy (MMN), one inclusion body myositis (IBM) and one myasthenia gravis (MG), treated with subcutaneous immunoglobulins for a mean of 3.25 years. RESULTS: One MMN and two CIDP patients received a weekly dose of subcutaneous immunoglobulins equivalent to intravenous immunoglobulin. One CIDP patient received a 50% dose reduction, the IBM patient received a 30% reduction and the MG patient a 20% reduction. The lower dose chosen in the majority of patients was based not only on clinical effects, but also on studies of primary immunodeficiency syndromes. One patient with CIDP showed clinical fluctuation, which was successfully treated with an adaptation of the dose of subcutaneous immunoglobulins, while the remaining patients with neuromuscular disorders had a stable clinical course for 2 years. No serious side effects were observed. CONCLUSIONS: Our results suggest that subcutaneous immunoglobulins can be an attractive alternative therapy in autoimmune neuromuscular disorders. PMID- 26136843 TI - The iontophoretic transdermal system formulation of sumatriptan as a new option in the acute treatment of migraine: a perspective. AB - An iontophoretic transdermal system (ITS) (skin patch) formulation of sumatriptan for the acute treatment of migraine attacks was approved by the US Food and Drug Administration in January 2013. This transdermal system bypasses the gastrointestinal tract, as it uses low electrical current to move sumatriptan transdermally into the subcutaneous tissue. Randomized, double-blind, controlled clinical trials have demonstrated minimal triptan-related side effects and superior efficacy versus placebo, comparable with other sumatriptan formulations. Sumatriptan ITS can be applied successfully during a mild or severe migraine attack. According to pharmacokinetic properties and clinical data, sumatriptan ITS may be a good choice for people with migraine and severe nausea, vomiting or gastroparesis, those with intolerable triptan-related adverse events and those not responding optimally to oral medications. PMID- 26136845 TI - A review of the efficacy and safety of eslicarbazepine acetate in the management of partial-onset seizures. AB - Eslicarbazepine acetate is a is a once-daily antiepileptic drug (AED) that was approved in 2009 by the European Medicines Agency (EMA) (ZebinixTM), and in 2013 by the US Food and Drug Administration (FDA) (AptiomTM) as adjunctive therapy in adults with refractory partial-onset seizures, with or without secondary generalization. It is a third-generation member of the dibenzazepine family of AEDs with distinctive mechanism of action, posology and tolerability profile. The eslicarbazepine acetate development program included an initial phase II study (study BIA 2-093) and three subsequent phase III, multicentre, randomized, double blinded and placebo-controlled clinical trials (studies BIA-2093-301, BIA- 2093 302 and BIA -2093-303). A fourth phase III placebo-controlled trial (study BIA 2093-304) was designed in order to meet specific requirements of the FDA. All performed studies have consistently shown that eslicarbazepine acetate (800 to 1200 mg/day) is effective and well tolerated as adjunctive therapy for adults with partial-onset seizures. PMID- 26136844 TI - Duchenne muscular dystrophy: current cell therapies. AB - Duchenne muscular dystrophy is a genetically determined X-linked disease and the most common, progressive pediatric muscle disorder. For decades, research has been conducted to find an effective therapy. This review presents current therapeutic methods for Duchenne muscular dystrophy, based on scientific articles in English published mainly in the period 2000 to 2014. We used the PubMed database to identify and review the most important studies. An analysis of contemporary studies of stem cell therapy and the use of granulocyte colony stimulating factor (G-CSF) in muscular dystrophy was performed. PMID- 26136846 TI - Intravenous fosphenytoin for acute exacerbation of trigeminal neuralgia: case report and literature review. PMID- 26136847 TI - Phylogenetically typing bacterial strains from partial SNP genotypes observed from direct sequencing of clinical specimen metagenomic data. AB - We describe an approach for genotyping bacterial strains from low coverage genome datasets, including metagenomic data from complex samples. Sequence reads from unknown samples are aligned to a reference genome where the allele states of known SNPs are determined. The Whole Genome Focused Array SNP Typing (WG-FAST) pipeline can identify unknown strains with much less read data than is needed for genome assembly. To test WG-FAST, we resampled SNPs from real samples to understand the relationship between low coverage metagenomic data and accurate phylogenetic placement. WG-FAST can be downloaded from https://github.com/jasonsahl/wgfast. PMID- 26136848 TI - InChI, the IUPAC International Chemical Identifier. AB - This paper documents the design, layout and algorithms of the IUPAC International Chemical Identifier, InChI. PMID- 26136849 TI - Feasibility and efficacy of diabetic retinopathy screening among youth with diabetes in a pediatric endocrinology clinic: a cross-sectional study. AB - BACKGROUND: We examined the feasibility and efficacy of using a non-mydriatic camera to screen for diabetic retinopathy (DR) among youth with type 1 or type 2 diabetes seen in a pediatric endocrinology clinic serving Alabama, the state that has the highest diabetes rate in the United States. METHODS: 236 youths with type 1 or type 2 diabetes were screened for DR using a non-mydriatic camera. Visual acuity was also assessed. A questionnaire asked parents about diabetes and eye care history. RESULTS: Mean duration since diabetes diagnosis was 5.5 years. 66 % reported receiving an eye examination within the previous year. 97.5 % had images that were gradable. DR was detected in 3.8 % of participants. 9.1 % were visually impaired. CONCLUSIONS: Use of a non-mydriatic fundus camera is feasible and efficacious for DR screening in youth with diabetes. DR screening at routine endocrinology visits may be beneficial in managing youth with diabetes and preventing irreversible vision loss, particularly for those in regions where diabetes rates are high. PMID- 26136850 TI - Degludec: the new ultra-long insulin analogue. AB - The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, "De") and the attachment, via a glutamic acid linker ("glu"), of a 16 carbon fatty diacid (hexadecanoic diacid, "dec") to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26-52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia. PMID- 26136851 TI - Systemic therapy in stage IV pancreatic cancer: a population-based analysis using the National Cancer Data Base. AB - BACKGROUND: Pancreatic cancer accounts for approximately 7% of all cancer deaths. More than half of all pancreatic cancers are stage IV at diagnosis, where systemic chemotherapy is used with the goal of life prolongation as well as palliation. The patient characteristics and health system factors that drive the use of systemic therapy are unknown. METHOD: This is a retrospective study of stage IV pancreatic cancer patients (n = 140,210) diagnosed between 2000 and 2011 in the NCDB. NCDB contains approximately 70% of new cancer diagnosis from more than 1500 accredited cancer programs in the United States and Puerto Rico. Chi squared test was used to determine any differences in characteristics of patients who did or did not receive systemic therapy. RESULTS: Our study demonstrated that only 49.1% of stage IV pancreatic cancer patients received systemic therapy. The use of systemic therapy is significantly lower in female, African American/Hispanic, patients older than 40 years, those without insurance or with Medicare and Medicaid, higher Charlson Comorbidity Score, poor economic and educational status and in nonacademic centers. CONCLUSIONS: This is the largest study to evaluate the determinants of systemic therapy use in stage IV pancreatic cancer. The use of systemic therapy was significantly lower in patients older than 40 years, lower educational status, nonprivate insurance and with higher Charlson Comorbidity Scores. In addition, the use of systemic therapy was lower with female sex, African Americans/Hispanic, and lower socio-economic status. Understanding the barriers in the use of systemic therapy as well as appropriate utilization of systemic therapy can both optimize cancer care. PMID- 26136852 TI - Vintafolide: a novel targeted therapy for the treatment of folate receptor expressing tumors. AB - Despite advances in the development of molecularly targeted therapies, limited improvements in overall survival have been noted among many cancer patients with solid tumors, primarily due to development of drug resistance. Accordingly, there is an unmet need for new targeted therapies and treatment approaches for cancer, especially for overcoming resistance. Expression of the folate receptor is upregulated in many tumor types and thus represents an ideal target for cancer treatment. Several folate receptor targeted therapies are in development, including the small molecule drug conjugate vintafolide, the monoclonal antibody farletuzumab, and the antibody-drug conjugate IMGN853. The role of the folate receptor as a target in cancer progression and resistance as well as emerging preclinical and clinical data from studies on those folate receptor targeted agents that are in development with a focus on vintafolide are reviewed. The folate receptor has several unique properties, such as high expression in several tumor types, that make it a rational target for cancer treatment, and allow for selective delivery of folate receptor targeted agents. Early-stage clinical data in lung and ovarian cancer suggest that vintafolide has the potential for combination with other standard approved agents. PMID- 26136855 TI - Corrigendum. AB - Stinchcombe, T. (2014) Novel agents in development for advanced non-small cell lung cancer. Ther Adv Med Oncol 6(5): 240-253. In the sentence on page 246, the subset analysis of patients with adenocarcinoma histology comprised 658 patients and not 568, as stated.[This corrects the article DOI: 10.1177/1758834014532510.]. PMID- 26136854 TI - Combination capecitabine and bevacizumab in the treatment of metastatic hepatic epithelioid hemangioendothelioma. AB - Hepatic epithelioid hemangioendothelioma (HEHE) is a rare, often misdiagnosed vascular neoplasm with clinical behaviors that range from indolent to highly aggressive. Even when the appropriate diagnosis is achieved, the best treatment for HEHE has not been defined or standardized, further complicating the care of these patients. We present a diagnostically challenging case of HEHE where we utilized capecitabine and bevacizumab as another novel treatment option. PMID- 26136853 TI - Bone-targeted agents in the treatment of lung cancer. AB - Over a third of patients with lung cancer will develop bone metastases during the course of their disease, resulting in symptoms of pain and immobility, and skeletal-related events (SREs) such as fracture, hypercalcaemia, surgery or radiotherapy to bones, and malignant spinal cord compression. These reduce quality of life and increase mortality. Preclinical research has identified the interactions between tumour cells and bone that are key to tumour cell survival and associated osteolysis. These data have led to the development of drugs to prevent osteoclast-mediated bone breakdown, such as zoledronic acid and denosumab, which are now licensed for use in patients with bone metastases from solid tumours. Both zoledronic acid and denosumab reduce the risk of SREs and increase time to first SRE, with minimal side effects. In addition, denosumab improved survival in patients with lung cancer compared with zoledronic acid. Ongoing trials are testing whether these drugs can prevent the development of bone metastases from lung cancer. New bone-targeted agents showing promise in breast and prostate cancer include radium-223, cabozantinib and Src inhibitors. These agents require further evaluation in patients with lung cancer. PMID- 26136856 TI - Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer's disease patients and healthy controls. AB - INTRODUCTION: Synaptic dysfunction and degeneration are central events in Alzheimer's disease (AD) pathophysiology that are thought to occur early in disease progression. Synaptic pathology may be studied by examining protein biomarkers specific for different synaptic elements. We recently showed that the dendritic protein neurogranin (Ng), including the endogenous Ng peptide 48 to 76 (Ng48-76), is markedly increased in cerebrospinal fluid (CSF) in AD and that Ng48 76 is the dominant peptide in human brain tissue. The aim of this study was to characterize Ng in plasma and CSF using mass spectrometry and to investigate the performance of plasma Ng as an AD biomarker. METHODS: Paired plasma and CSF samples from patients with AD (n = 25) and healthy controls (n = 20) were analyzed in parallel using an immunoassay developed in-house on the Meso Scale Discovery platform and hybrid immunoaffinity-mass spectrometry (HI-MS). A second plasma material from patients with AD (n = 13) and healthy controls (n = 17) was also analyzed with HI-MS. High-resolution mass spectrometry was used for identification of endogenous plasma Ng peptides. RESULTS: Ng in human plasma is present as several endogenous peptides. Of the 16 endogenous Ng peptides identified, seven were unique for plasma and not detectable in CSF. However, Ng48 76 was not present in plasma. CSF Ng was significantly increased in AD compared with controls (P < 0.0001), whereas the plasma Ng levels were similar between the groups in both studies. Plasma and CSF Ng levels showed no correlation. CSF Ng was stable during storage at -20 degrees C for up to 2 days, and no de novo generation of peptides were detected. CONCLUSIONS: For the first time, to our knowledge, we have identified several endogenous Ng peptides in human plasma. In agreement with previous studies, we show that CSF Ng is significantly increased in AD as compared with healthy controls. The origin of Ng in plasma and its possible use as a biomarker need to be further investigated. The results suggest that CSF Ng, in particular Ng48-76, might reflect the neurodegenerative processes within the brain, indicating a role for Ng as a potential novel clinical biomarker for synaptic function in AD. PMID- 26136858 TI - Research into europium complexes as magnetic resonance imaging contrast agents (Review). AB - Europium (Eu) is a paramagnetic lanthanide element that possesses an outstanding luminescent property. Eu complexes are ideal fluorescence imaging (FI) agents. Eu2+ has satisfactory relaxivity and optical properties, and can realize magnetic resonance (MRI)-FI dual imaging applications when used with appropriate cryptands that render it oxidatively stable. By contrast, based on the chemical exchange saturation transfer (CEST) mechanism, Eu3+ complexes can provide enhanced MRI sensitivity when used with optimal cryptands, incorporated into polymeric CEST agents or blended with Gd3+. Eu complexes are promising in MRI-FI dual imaging applications and have a bright future. PMID- 26136857 TI - Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration. AB - Alzheimer's disease (AD) is recognized to have a long presymptomatic period, during which there is progressive accumulation of molecular pathology, followed by inexorable neuronal damage. The ability to identify presymptomatic individuals with evidence of neurodegenerative change, to stage their disease, and to track progressive changes will be important for early diagnosis and for prevention trials. Despite recent advances, particularly in magnetic resonance imaging, our ability to identify early neurodegenerative changes reliably is limited. The development of diffusion-weighted magnetic resonance imaging, which is sensitive to microstructural changes not visible with conventional volumetric techniques, has led to a number of diffusion imaging studies in AD; these have largely focused on white matter changes. However, in AD cerebral grey matter is affected very early, with pathological studies suggesting that grey matter changes predate those in white matter. In this article we review the growing number of studies that assess grey matter diffusivity changes in AD. Although use of the technique is still at a relatively early stage, results so far have been promising. Initial studies identified changes in diffusion measures in the hippocampi of patients with mild cognitive impairment, which predated macroscopic volume loss, with positive predictive value for progression to AD dementia. More recent studies have identified abnormalities in multiple neocortical areas (particularly the posterior cingulate) at various stages of disease progression. Studies of patients who carry genetic mutations predisposing to autosomal dominant familial AD have shown cortical and subcortical grey matter diffusivity changes several years before the expected onset of the first clinical symptoms. The technique is not without potential methodological difficulties, especially relating to partial volume effects, although recent advances appear to be reducing such issues. Going forward, further utilization of grey matter diffusion measurements in AD may improve our understanding with regards to the timing and nature of the earliest presymptomatic neurodegenerative changes. This imaging technique may also be useful in comparing and contrasting subtle variations in different disease subgroups, and as a sensitive outcome measure for presymptomatic clinical trials in AD and other neurodegenerative diseases. PMID- 26136859 TI - Role of basophils in rheumatoid arthritis (Review). AB - The T helper (Th)1/Th2 imbalance plays a crucial role in the development of rheumatoid arthritis (RA). It is well known that basophils can affect the Th1/Th2 balance by enhancing the Th2 response, while impairing the Th1 response, which is known to be involved in the development of a number of diseases. However, limited information is available with regard to the role of basophils in RA. Decreased levels of circulating basophils and a dominant Th1 response have been reported in adult patients with RA, while children with juvenile RA have been largely found to have increased levels of circulating basophils and a dominant Th2 response. Furthermore, the circulating basophils in the two conditions have an activated phenotype and are associated with disease activity. In addition, a longitudinal study found the Th2 response was dominant in the early stages of RA, while the Th1 response was dominant in long-term chronic RA. These observations indicate that basophils may be involved in the development of RA by affecting the Th1/Th2 balance, particularly in the early stages of RA. Therefore, targeting basophils may be a novel therapeutic strategy for the treatment of RA; however, further investigation is required. PMID- 26136860 TI - Association between preeclampsia and the CXC chemokine family (Review). AB - Preeclampsia is a major cause of maternal and perinatal mortality and morbidity, characterized by gestational hypertension, proteinuria, systemic endothelial cell activation and an exaggerated inflammatory response. The precise cause of preeclampsia is not currently known; however, it is widely accepted that the pathogenesis of preeclampsia involves inadequate trophoblast invasion, leading to generalized endothelial dysfunction and an exaggerated inflammatory response. Chemokines are a superfamily of structurally similar proteins that mediate cell recruitment, angiogenesis, immunity and stem cell trafficking. CXC chemokines are a family of cytokines, unique in their ability to behave in a disparate manner in the regulation of angiogenesis. The CXC chemokine family further divides into two subfamilies; CXC ELR+, which promotes angiogenesis, and CXC ELR-, which inhibits angiogenesis. Furthermore, CXC chemokines are involved in the pathogenesis of various conditions, including malignant tumors, wound repair, chronic inflammation, atherosclerosis and potentially preeclampsia. PMID- 26136861 TI - Acupuncture: Emerging evidence for its use as an analgesic (Review). AB - Acupuncture is an ancient Chinese technique, developed over >3,000 years, in which 'acupoints' are stimulated with the aim of treating various diseases. A number of previous studies have indicated that acupuncture may play a role in inducing analgesia. Acupuncture-induced analgesia has been hypothesized to act on various parts of the central nervous system, including the spinal cord, brain stem, cerebral ganglia and cerebral cortex. The mechanisms underlying the effects of acupuncture have been purported to include neurohumors and neurotransmitters, such as opioids and gamma-aminobutyric acid, signaling pathways and the immune response, which are all involved in the induction of analgesia. PMID- 26136862 TI - Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review). AB - Caffeic acid phenethyl ester (CAPE), a naturally occurring compound isolated from propolis extract, has been reported to have a number of biological and pharmacological properties, exerting antioxidant, anti-inflammatory, anticarcinogenic, antibacterial and immunomodulatory effects. Recent in vivo and in vitro study findings have provided novel insights into the molecular mechanisms involved in the anti-inflammatory and immunomodulatory activities of this natural compound. CAPE has been reported to have anti-inflammatory properties involving the inhibition of certain enzyme activities, such as xanthine oxidase, cyclooxygenase and nuclear factor-kappaB (NF-kappaB) activation. Since inflammation and immune mechanisms play a crucial role in the onset of several inflammatory diseases, the inhibition of NF-kappaB represents a rationale for the development of novel and safe anti-inflammatory agents. The primary goal of the present review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, and critically evaluate its potential therapeutic effects. PMID- 26136863 TI - Efficacy of different irrigation solutions on the early debridement of open fracture in rats. AB - Contaminating bacteria are only found on wound surfaces in the initial stages of open fractures; therefore, effective debridement is critical for bacterial infection prevention and the reduction of inflammatory reactions. Various irrigation solutions are currently being used; however, a comprehensive study on their efficacy is lacking. In the present study, a comparison of the effects of normal saline, iodophor and hydrogen peroxide as the irrigation solutions for debridement of open femur fractures in rat models was conducted. It was revealed that all three solutions were comparably effective in bacterial removal while normal saline was superior in minimizing adverse wound inflammation; therefore, the use of normal saline for routine debridement is recommended in the early stage treatment of open fractures in the trauma clinic and in relief fieldwork. PMID- 26136864 TI - Protective effect of probiotics in the treatment of infantile eczema. AB - The aim of the present study was to provide evidence for the application of probiotics in the prevention and treatment of infantile eczema by exploring changes in the intestinal Bifidobacteria levels and the Scoring Atopic Dermatitis (SCORAD) index prior and subsequent to treatment with probiotics in infants with eczema. A total of 40 infants with eczema were randomly divided into treatment and control groups. Prior and subsequent to the treatment, the SCORAD index was evaluated and the content of Bifidobacterium bifidum in the stool of each infant in the two groups was quantified using 16S rRNA/DNA quantitative polymerase chain reaction analysis. After four weeks of treatment with B. bifidum triple viable capsules, the levels of B. bifidum increased sharply (P<0.05) and the SCORAD index was notably reduced (P<0.05) as compared with the values prior to treatment. By contrast, neither the content of B. bifidum nor the SCORAD index changed significantly in the control group after four weeks (P>0.05). Following treatment, the levels of B. bifidum in the stools of the treatment group were significantly higher than those in the stools of the control group (P<0.05), and the SCORAD index was significantly lower than that of the control group (P<0.05). In conclusion, probiotic supplementation has a positive effect on the prevention and treatment of infantile eczema. PMID- 26136865 TI - Increased glyceraldehyde-3-phosphate dehydrogenase expression indicates higher survival rates in male patients with hepatitis B virus-accociated hepatocellular carcinoma and cirrhosis. AB - Elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been reported in different human malignancies. To understand its role in hepatitis B virus (HBV) infection-associated hepatocellular carcinoma (HCC), the expression of GAPDH was quantitatively measured in a cohort of 72 male HCC patients without preoperative treatment, all with evidence of chronic HBV infection. Using C terminal banding protein 1 (CTBP1) or hypoxanthine phosphori-bosyltransferase 1 (HPRT1) as reference genes, the level of GAPDH mRNA in tumor tissue was found to be significantly higher compared with that in paired non tumor tissues (P=0.0087 for CTBP1; P=0.0116 for HPRT1). Accordingly, compared with the non-tumor tissue, 37.5% (27/72) of patients' tumor tissues had a more than 2-fold increase of GAPDH expression. Furthermore, following knockdown GAPDH expression via siRNA transient transfection, HepG2 cells exhibited enhanced resistance to cytosine arabinoside (IC50, 308.28 uM vs. 67.68 uM in the control; P=0.01). Notably, higher GAPDH expression was significantly associated with lower liver fibrosis score (P=0.0394) and a tendency towards higher survival rates for patients with HCC. To the best of our knowledge, the present study is the first study to report that the elevated expression levels of GAPDH in HCC tumor tissue may be relevant to an improved fibrosis score and survival probability in male patients with HBV infection; however, the underlying mechanism requires further investigation. PMID- 26136866 TI - Potential role of recombinant adeno-associated virus human thioredoxin-PR39 in cell and vascular protection against hypoxia. AB - The aim of the present study was to successfully construct a recombinant adeno associated virus (rAAV) vector containing the human thioredoxin (hTRX)-PR39 chimeric gene (rAAV/hTRX-PR39), and verify that the vector was able to maintain a sustained, stable and efficient expression to achieve protein production in the cell. In the present study, a chicken embryo model was utilized to analyze the therapeutical effect of rAAV/hTRX-PR39 in cerebral ischemia diseases. ECV304 cells were transfected with rAAV/hTRX-PR39 and incubated under conditions of 20, 5 and 1% O2. Subsequently, the expression levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, fibroblast growth factor receptor (FGFR)-1 and syndecan-4 were detected by reverse transcription-quantitative polymerase chain reaction. Under hypoxic conditions, the mRNA expression levels of VEGF, VEGFR-1, VEGFR-2, FGFR-1 and syndecan-4 were found to increase in the PR39-transfected group when compared with the control group, while no statistically significant difference was observed between the PR39-transfected group and the control group under conditions of 20% O2. In addition, hTRX-PR39 was shown to increase the density of the vasculature and the survival rate of the chick embryos. Under hypoxic conditions, it was hypothesized that rAAV/hTRX-PR39 was capable of promoting angiogenesis, which may subsequently protect the cells from impairment by hypoxia. In conclusion, rAAV/hTRX-PR39 was demonstrated to promote vascularization and cell survival in hypoxia; thus, rAAV/hTRX-PR39 may have potential for use in therapy targeting cerebral ischemia. PMID- 26136867 TI - Association between follicular fluid levels of HMGB1 protein and outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection cycles. AB - The aim of the present study was to evaluate the association between follicular fluid (FF) levels of high-mobility group box 1 (HMGB1) protein and the reproductive outcome in patients undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). FF samples were collected from the ovarian follicles (>=14 mm) of 143 infertile patients that had undergone IVF/ICSI, and the HMGB1 expression levels were determined using ELISA. Spearman's correlation and receiver operating characteristic (ROC) curve analysis were applied to analyze the results. Significantly increased levels of HMGB1 protein (7.38+/-2.02 vs. 6.14+/-2.52 ng/ml; P<0.01), endometrial thickness on the day of human chorionic gonadotropin (hCG) administration (10.3+/-1.3 vs. 9.7+/-1.7 mm; P<0.01) and retrieved oocyte counts (11.68+/-6.51 vs. 11.00+/-6.34; P<0.01) were observed in the pregnant group when compared with the non-pregnant group. Conversely, the level of luteinizing hormone on the day of hCG administration was significantly reduced in the pregnant group compared with the non-pregnant group (0.92+/-1.78 vs. 1.78+/-2.03 pmol/l, P<0.01). The ROC curve indicated a significant association between the FF level of HMGB1 protein and the pregnancy rate, with an area under the ROC curve of 0.673 (0.581-0.765; P<0.01). In addition, the HMGB1 protein level was shown to have a significant positive correlation with the endometrial thickness (r=0.170; P<0.05). Therefore, the present study indicated that the FF levels of HMGB1 protein are increased in pregnant patients and are positively correlated with endometrial thickness. Thus, FF levels of HMGB1 may be a useful factor for predicting the outcome of IVF/ICSI treatments. PMID- 26136868 TI - microRNA-425-5p is upregulated in human gastric cancer and contributes to invasion and metastasis in vitro and in vivo. AB - Emerging evidence indicates that microRNAs are involved in the development and progression of gastric cancer (GC), functioning as tumor suppressors or oncogenes. The aim of the current study was to explore the potential mechanism of microRNA-425-5p (miR-425-5p) in GC. Using reverse transcription quantitative polymerase chain reaction, miR-425-5p expression was detected in GC cell lines (SGC-7901, MKN-28, MKN-45, BGC-823 and AGS) and the GES-1 cell line. Cell proliferation, soft agar colony formation, flow cytometry, haptotactic migration and matrigel chemoinvasion assays were used to test the proliferation, apoptosis, invasion and migration of BGC-823 cells transfected with miR-425-5p mimics or an inhibitor. Female BALB/c mice were randomly divided into three groups. Each experimental group contained five mice. BGC 823 cells were stably transfected with miR-425-5p inhibitor, wild type or negative control and were injected into the mice through the tail vein. It was found that miR-425-5p expression was significantly upregulated in all the GC cell lines when compared with the GES-1 cell line. Downregulation of miR-425-5p expression inhibited GC cell proliferation, invasion and migration. In the in vivo studies, downregulation of miR-425-5p expression suppressed pulmonary metastasis in the nude mice. Thus, miR 425-5p was demonstrated to have the potential to become a novel metastasis associated gene; however, the mechanisms associated with these effects require further study. In the future, the development of miR-425-5p as a novel therapeutic strategy for the treatment of GC may be possible. PMID- 26136869 TI - Therapeutic efficacy of umbilical cord-derived mesenchymal stem cells in patients with type 2 diabetes. AB - Type 2 diabetes (T2D) is characterized by progressive and inexorable beta-cell dysfunction, leading to insulin deficiency. Novel strategies to preserve the remaining beta-cells and restore beta-cell function for the treatment of diabetes are urgently required. Mesenchymal stem cells (MSCs) have been exploited in a variety of clinical trials aimed at reducing the burden of immune-mediated disease. The aim of the present clinical trial was to assess the safety and efficacy of umbilical cord-derived MSC (UCMSC) transplantation for patients with T2D. The safety and efficacy of UCMSC application were evaluated in six patients with T2D during a minimum of a 24-month follow-up period. Following transplantation, the levels of fasting C-peptide, the peak value and the area under the C-peptide release curve increased significantly within one month and remained high during the follow-up period (P<0.05). Three of the six patients became insulin free for varying lengths of time between 25 and 43 months, while the additional three patients continued to require insulin injections, although with a reduced insulin requirement. Fasting plasma glucose and 2-h postprandial blood glucose levels were relatively stable in all the patients following transplantation. There was no immediate or delayed toxicity associated with the cell administration within the follow-up period. Therefore, the results indicated that transplantation of allogeneic UCMSCs may be an approach to improve islet function in patients with T2D. There were no safety issues observed during infusion and the long-term monitoring period. PMID- 26136870 TI - Batroxobin protects against spinal cord injury in rats by promoting the expression of vascular endothelial growth factor to reduce apoptosis. AB - The host response to spinal cord injury (SCI) can lead to an ischemic environment that can induce cell death. Therapeutic interventions using neurotrophic factors have focused on the prevention of such reactions in order to reduce this cell death. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. We hypothesized in this study that batroxobin would exhibit protective effects following SCI by promoting the expression of VEGF to reduce the levels of apoptosis in a rat model of SCI. Ninety adult female Sprague Dawley rats were divided randomly into sham injury (group I), SCI (group II) and batroxobin treatment (group III) groups. The Basso-Bettie-Bresnahan (BBB) scores, number of apoptotic cells and expression of VEGF were assessed at 1, 3, 5, 7, 14 and 28 days post-injury. The BBB scores were significantly improved in group III compared with those in group II between days 5 and 28 post-injury (P<0.05). At each time-point subsequent to the injury, the number of apoptotic cells in group III was reduced compared with that in group II. Compared with group II, treatment with batroxobin significantly increased the expression of VEGF from day 3 until 2 weeks post-SCI (P<0.05), while no significant difference was observed at day 28. These data suggest that batroxobin has multiple beneficial effects on SCI, indicating a potential clinical application. PMID- 26136871 TI - Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome. AB - Brugada syndrome (BrS) is a rare, inherited arrhythmia syndrome. The most well known gene that is responsible for causing BrS is SCN5A, which encodes the human cardiac Na+ channel (Nav1.5) alpha subunit. To date, it has been reported that >100 mutations in SCN5A can cause BrS. In the present study, a novel BrS associated Nav1.5 mutation, A1428S, was identified in a proband who was successfully resuscitated from an episode of sudden collapse during walking. This mutation was further confirmed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis, which showed that the PCR fragment containing the mutation A1428S could be cut by the restriction enzyme Nsi1, yielding two shorter DNA fragments of 329 and 159 bp, which were not present in family members homozygous for the wild-type (WT) allele. Furthermore, the electrophysiological properties were analyzed by patch clamp technique. Current density was decreased in the A1428S mutant compared that in the WT. However, neither the steady-state activation or inactivation, nor the recovery from inactivation exhibited changes between the A1428S mutant and the WT. In conclusion, the results of this study are consistent with the hypothesis that a reduction in Nav1.5 channel function is involved in the pathogenesis of BrS. The structural-functional study of the Nav1.5 channel enhances the present understanding the pathophysiological function of the channel. PMID- 26136872 TI - Prediction of a sustained viral response in chronic hepatitis C patients who undergo induction therapy with double filtration plasmapheresis plus interferon beta/ribavirin. AB - The aim of the present study was to determine predictors of a sustained virological response (SVR) with a regimen of double filtration plasmapheresis (DFPP) combined with interferon-beta plus ribavirin (IFN-beta/RBV) induction therapy prior to pegylated (PEG-IFN/RBV) standard of care (SOC) therapy for patients with chronic hepatitis C who had experienced SOC treatment failure. Predictors of a SVR were analyzed in chronic hepatitis C patients with genotype 1b hepatitis C virus (HCV), who had a high viral load. The patients had been unresponsive to previous IFN therapy and underwent induction therapy with IFN beta/RBV plus DFPP, which was performed five times during the same period, followed by PEG-IFN/RBV. In total, 10 patients received the combination DFPP plus IFN-beta/RBV induction therapy prior to PEG-IFN/RBV therapy for the treatment of chronic hepatitis C. Two weeks after treatment initiation, a decrease in the HCV RNA levels of >=2 log IU/ml occurred in 9/10 patients (90%), while a decrease of >=4 log IU/ml was observed in 4/10 patients (40%). The HCV RNA levels at week 2 after treatment initiation in the SVR and non-SVR patients decreased by 5.0+/-0.8 and 2.9+/-1.1 log IU/ml, respectively. Despite no response to previous IFN therapy, three of the 10 patients (30%) experienced a SVR. The results indicated that a rapid virological response ensued following IFN-beta/RBV induction and DFPP supplementary therapy. Although the level of interleukin-28B is an important predictor of a SVR, a decrease in the HCV RNA volume of >=4 log IU/ml at week 2 after the initial treatment is also an important predictor. Therefore, rapid virological reduction using DFPP, in addition to IFN-beta/RBV induction therapy, is an important predictor of a SVR. PMID- 26136873 TI - Ulinastatin enhances the therapeutic effect of intraperitoneal lavage on severe acute pancreatitis in rats. AB - The present study investigated the therapeutic effect of peritoneal lavage with ulinastatin on the outcome of rats with severe acute pancreatitis (SAP). A total of 110 male Wistar rats were randomly divided into the following groups: Control (C), SAP model (SAP), saline lavage (SL), intravenous ulinastatin (IU) and low dose (LUL), medium-dose (MUL), high-dose (HUL) and ultrahigh-dose (UHUL) ulinastatin lavage. The treatments were performed immediately subsequent to the establishment of the SAP model. Intraperitoneal lavage with or without ulinastatin was performed for 3 h. Survival time was recorded for 12 h and the median survival time was calculated. Histopathological analyses, and measurements of plasma amylase and lipase levels were performed. Blood pH, lactic acid and base excess were also detected. The LUL, MUL, HUL, UHUL and IU groups showed an increase in the median survival time compared with the SAP group, with the maximal effect observed in the MUL group (P<0.01). The SL, MUL and IU groups showed a reduced activity of amylase and lipase compared with the SAP group. The SL (P<0.01) and the MUL groups (P<0.01) additionally showed a reduction in the lactic acid in arterial blood relative to the SAP group but the IU group did not. The MUL group showed greater improvements in pH (P<0.01) and base excess (P<0.01) versus the SAP group than the SL and IU groups. Furthermore the MUL group demonstrated a more marked reduction in the histological changes in necrosis, edema and inflammation compared with the SL and IU groups. Intraperitoneal lavage with ulinastatin significantly improves the prognosis of SAP in rats. PMID- 26136874 TI - Percutaneous coronary intervention strategies and prognosis for graft lesions following coronary artery bypass grafting. AB - The purpose of this study was to compare the prognosis of graft-percutaneous coronary intervention (PCI) and native vessel (NV)-PCI, drug-eluting stents (DESs) and bare-metal stents (BMSs) for the treatment of graft lesions following coronary artery bypass grafting (CABG), and to determine the risk factors for major adverse cardiac events (MACEs). A total of 289 patients who underwent PCI following CABG between August 2005 and March 2010 were retrospectively analyzed. The effects on survival were compared among patients who underwent NV- and graft PCI, and DES and BMS implantation. Additionally, the risk factors for MACEs following PCI for graft lesions were analyzed. The findings showed that MACE-free and revascularization-free survival rates were significantly higher in the NV-PCI group compared with those in the graft-PCI group. There were 63 cases (29.0%) of MACEs in the DES group and 25 cases (52.1%) in the BMS group. In patients undergoing NV-PCI, the DES group had significantly fewer MACEs and less target vessel revascularization (TVR) than the BMS group. In patients undergoing graft PCI, the DES group showed a tendency for fewer MACEs and a lower incidence of cardiac mortality, myocardial infarction and TVR compared with the BMS group. Diabetes, an age of >70 years and graft-PCI were independent risk factors for MACEs in patients post-PCI. It is concluded that NV-PCI has superior long-term outcomes compared with graft-PCI, and should therefore be considered as the first line treatment for graft disease following CABG. Despite this, graft-PCI remains a viable option. DESs are the first choice for graft-PCI due to their safety and efficacy and their association with reduced mortality and MACE rate. Diabetes, older age and graft-PCI are independent risk factors for MACEs in patients post CABG who are undergoing revascularization. PMID- 26136875 TI - Effect of baicalein on the expression of SATB1 in human breast cancer cells. AB - The aim of the present study was to investigate the effects of baicalein on the protein expression of SATB1 in the MDA-MB-231 human breast cancer cell line. MDA MB-231 cells were treated with various concentrations of baicalein (0, 10, 20, 40 uM). Following treatment, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and wound healing assay were used to detect the changes in cell proliferation and migration. In addition, western blot analysis was performed to detect the changes in the protein expression levels of SATB1 in the MDA-MB-231 cell line. With the prolongation of administration time and the increase in drug concentration, the inhibitory effect of baicalein on the proliferation and migration of MDA-MB-231 cells gradually increased in a time- and dose-dependent manner (P<0.05). In addition, baicalein was shown to markedly decrease the protein expression levels of SATB1 in the MDA-MB-231 cells. With increasing drug concentrations, the protein expression levels of SATB1 decreased gradually (P<0.05). Therefore, baicalein was demonstrated to inhibit the proliferation of MDA-MB-231 cells and downregulate the protein expression of SATB1, indicating that baicalein can significantly inhibit the proliferation, migration and invasiveness of MDA-MB-231 cells by downregulating the expression of SATB1. PMID- 26136876 TI - Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats. AB - The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-alpha, IL-1beta and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF and NGF was also ameliorated by Gs treatment. Histological analysis indicated that Gs corrected the sciatic tissue in the diabetic rats. Therefore, the results demonstrated that the neuroprotective effect of Gs may be associated with the inhibitory effect on the excessive activation of inflammatory molecules and oxidative stress mediators. PMID- 26136877 TI - Effects of anesthesia on conventional and speckle tracking echocardiographic parameters in a mouse model of pressure overload. AB - Genetically-modified mice are widely applied in cardiovascular studies as model organisms. Echocardiography is a key tool for evaluating cardiac and hemodynamic functions in mice. The present study aimed to examine the effects of isoflurane (ISF) on conventional and speckle tracking echocardiography (STE) parameters under healthy and pathological conditions using a murine model of pressure overload. In addition, the optimal dose of ISF in the process of echocardiographic measurement, with minimum cardiac contraction depression, was investigated. Conventional echocardiographic and STE examinations were performed on 38 adult C57BL/6 male mice. The mice were divided into the following three groups: The sham (n=15); mild thoracic aortic banding (TAB; n=15); and severe TAB (n=8) groups. ISF was administered under deep anesthesia (DA; 1-2% ISF), light anesthesia (LA; 0.5-1% ISF) and immediately prior to the mice waking up (awake; 0 0.5% ISF). Conventional echocardiographic parameters were preserved within the sham and mild TAB groups (P>0.05 for each parameter) under LA and awake conditions. However, under DA conditions, the majority of these parameters were reduced compared with the LA and awake conditions (P<0.05). In the severe TAB group, conventional echocardiographic parameters remained constant under LA, DA and awake conditions. STE parameters in the groups remained similar between the LA and awake conditions, but were significantly reduced under DA conditions. Therefore, conventional echocardiography and STE may be performed using LA induced with low doses of ISF, under various pathological conditions without affecting cardiac function. PMID- 26136878 TI - A preliminary investigation of EZSCANTM screening for impaired glucose tolerance and diabetes in a patient population. AB - EZSCANTM is a non-invasive technology that evaluates sweat gland dysfunction using electrochemical skin conductance measurements, providing an opportunity to determine the risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). This study was conducted with the aims of detecting IGT and DM and investigating the efficacy and cut-off points of the EZSCAN test in a patient population. The traditional serum and plasma glucose tests were used as comparators. In this cross-sectional study, 270 previously undiagnosed patients (180 women and 90 men) with a high risk of glucose metabolism disorders (>=45 years old) were enrolled. All patients underwent an oral glucose tolerance test (OGTT) and hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and EZSCAN tests. Forty (14.8%) patients had newly diagnosed DM (NDM), 79 (29.3%) had IGT and 151 (55.9%) had normal glucose tolerance. The EZSCAN values of these groups were 48+/ 11, 47+/-11 and 34+/-13%, respectively. For all patients, the correlation coefficient of EZSCAN was 0.462 with the OGTT (P<0.001), 0.182 with the FPG test (P<0.001) and 0.379 with the HbA1c test (P<0.001). The EZSCAN cut-off point for the detection of IGT was 37% [sensitivity, 82%; specificity, 62%; area under the curve (AUC), 0.778], and the cut-off point for NDM was 50% (sensitivity, 53%; specificity, 59%; AUC, 0.528). This study demonstrated that the non-invasive EZSCAN system is an effective screening tool for the detection of glucose dysfunction in the population tested, and that its performance in detecting previously undiagnosed IGT is superior to its performance in detecting DM. PMID- 26136879 TI - Neuroprotective effect of interleukin-6 in a rat model of cerebral ischemia. AB - Interleukin (IL)-6 is known to be a key cytokine in immune regulation in addition to serving crucial functions in various autoimmune diseases; however, the neuroprotective potential of IL-6 has not been fully investigated. The aim of the present study was to investigate the neuroprotective effects of the inflammatory cytokine IL-6 in a rat model of cerebral ischemia. Rat cerebral ischemia was induced by intraluminal middle cerebral artery occlusion. Following treatment with 500 or 50 ng IL-6, the infarct volumes and symptoms of neurological deficit were ameliorated. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining suggested that the IL-6 treatment reduced neuronal apoptosis in vivo, which was consistent with a lower percentage of annexin V- and caspase-3-positive cortical neurons. In addition, IL-6 in vitro induced the phosphorylation of signal transducer and activator of transcription (STAT) 3 and the expression of induced myeloid leukemia cell differentiation protein Mcl-1, but not the expression of B-cell lymphoma 2, suggesting the activation of the Janus kinase/STAT pathway by IL-6. IL-6 also appeared to be involved in the regulation of cytokine secretion and blood-brain barrier (BBB) integrity in cerebral ischemia. IL-6 downregulated a number of inflammatory cytokines, including tumor necrosis factor-alpha and IL-1beta, as well as myeloperoxidase activity, indicating the accumulation of granulocytes in the ischemic brain tissue. IL-6 was also observed to support the integrity of the BBB by reducing Evans blue leakage in vivo and suppressing the expression of matrix metalloproteinase-9 in ischemic brain tissue. In conclusion, the results of the present study indicate that the neuroprotective effects of IL-6 in cerebral ischemia are the result of a range of processes, including the modulation of cell apoptosis, cytokine secretion and the integrity of the BBB. IL-6 could therefore be used as a therapeutic agent in clinical practice. PMID- 26136880 TI - Antihypertensive treatment improves left ventricular diastolic function in patients with chronic kidney disease. AB - In patients with chronic kidney disease (CKD), hypertension (HP) is associated with the development of left ventricular (LV) diastolic dysfunction. However, the impact of antihypertensive treatment on LV diastolic function has not been well studied in CKD patients. Recently, two-dimensional speckle-tracking echocardiography (2DSTE) has emerged as a sensitive and quantitative assessment of LV diastolic function. The present study used 2DSTE to investigate the effects of antihypertensive treatment on LV diastolic function in patients with CKD and untreated HP. The study comprised 134 patients with CKD and untreated HP. The patients received blood pressure (BP)-lowering therapy for six months. The patients were clinically and echocardiographically evaluated at baseline and after 6 months of therapy. It was found that the mean systolic BP (SBP) and diastolic BP (DBP) at baseline were 154.0+/-7.0 and 92.6+/-10.2 mmHg, respectively, decreasing to 121.2+/-7.3 and 74.6+/-10.4 mmHg, respectively (P<0.05 for both) after the 6-month treatment period. Moreover, the mean peak LV strain rate during the isovolumetric relaxation period (SRIVR) and early diastole (SRE) improved following treatment (from 0.23+/-0.10 to 0.42+/-0.10 sec-1 and from 0.58+/-0.25 to 1.07+/-0.24 sec-1, respectively; P<0.05 for both). Notably, the patients with CKD stage >=3 were more likely to demonstrate an improvement in diastolic speckle-tracking parameters than those with CKD stage 1 or 2. For the entire population, the change (Delta) in B-type natriuretic peptide (BNP) level correlated with changes in echocardiographic parameters between baseline and follow-up, among which DeltaSRIVR presented the highest correlation coefficient (r=-0.73, P<0.01). On multivariate analysis, the independent predictors of DeltaSRIVR were found to include baseline CKD stage, SBP and SRIVR. This study demonstrated that LV diastolic function was improved in CKD patients following antihypertensive treatment, particularly in patients with CKD stage >=3, higher baseline SBP and worse LV diastolic function. These results highlight the importance of BP reduction in the treatment of CKD. PMID- 26136881 TI - Cidan inhibits liver cancer cell growth by reducing COX-2 and VEGF expression and cell cycle arrest. AB - Cidan is a traditional Chinese medicine formula that has been used for >10 years as an antitumor drug. In the present study, the antitumor effect of cidan on hepatocellular carcinoma (HCC) and the underlying molecular mechanisms were investigated. A total of 372 patients with primary HCC, as confirmed by pathological examination in the Eastern Hepatobiliary Surgery Hospital and Beijing Oncology Hospital of Weida TCM, were prospectively enrolled in the study. In total, 92 patients were treated with cidan capsules for three months postoperatively, while 280 patients served as controls. The efficacy of cidan was analyzed by monitoring associated symptoms and liver function tests, including measuring the levels of alpha-1-fetoprotein, alpha-L-fucosidase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase. In addition, in vivo analysis was performed using mice Hepa1-6 xenograft models, while in vitro studies were performed with SMMC-7721 and CSQT-1 cells; this included cidan-dependent cell viability and migration assays, cell cycle analyses and the evaluation of cidan effects on cyclooxygenase 2 (COX-2) and vascular endothelial growth factor (VEGF) mRNA transcription rates using quantitative polymerase chain reaction. The postoperative two-year overall survival (77 and 58% for the cidan and control groups, respectively; P<0.01) and disease-free survival (36 and 24% for the cidan and control groups, respectively; P<0.01) rates were superior in the cidan-treated group when compared with the control. In addition, the size and weight of the tumor xenografts in the C57BL/6 mice were significantly reduced in a time- and dose-dependent manner following cidan treatment (P<0.01). Cidan significantly reduced the cell viability of SMMC 7721 and CSQT-1 cells after four and five days when compared with the control (P<0.01). Furthermore, COX-2 and VEGF mRNA expression levels decreased following cidan treatment (P<0.01), and cidan treatment resulted in enhanced G1 and G2/M cell cycle arrest of CSQT-1 cells. Therefore, cidan effectively inhibited cell proliferation, reduced cell viability and downregulated COX-2 and VEGF expression levels in hepatoma cells. PMID- 26136882 TI - Intra-tumor heterogeneity of BRAF V600E mutation in lung adenocarcinomas. AB - BRAF mutations exist in numerous types of cancer, including melanomas, colorectal cancers and lung cancers. The V600E-specific inhibitor vemurafenib has marked clinical activity in patients with BRAF V600E-mutated melanoma. However, there are many cases of resistance to vemurafenib. This may be due to the reported intra-tumor heterogeneity of the BRAF V600E mutation in primary melanomas. BRAF mutations are found in 1-5% of non-small cell carcinomas (NSCLCs), almost exclusively in adenocarcinoma. A few cases have been reported in which vemurafenib was effective against BRAF V600E-mutated lung cancers. In a previous study, five lung adenocarcinomas with BRAF V600E mutation were detected by direct sequencing. The present study analyzed these tumors for the percentage of mutation (%mutation) by competitive allele-specific polymerase chain reaction (CAST-PCR) assay. In addition, sections of all components of the adenocarcinomas were obtained by laser microdissection and analyzed. The %mutations of BRAF V600E within the macrodissected tumors (cases 1-5) were: Case 1, 10.0%; case 2, 8.0%; case 3, 8.9%; case 4, 21.5%; and case 5, 14.9%. In four cases (cases 2-5), the %mutations of each adenocarcinoma component were as follows: Case 2, lepidic growth 6.5-24.5%, papillary 1.3-11.2% and acinar 9.8%; case 3, solid 2.5-69.9%, acinar 12.4-27.1% and papillary 3.7-17.4%; case 4, acinar 10.0-45.0% and papillary 44.0%; and case 5, papillary 3.7-93.4%. Sensitive BRAF mutation detection methods were used and evidence for heterogeneity of the BRAF V600E mutation in these lung adenocarcinoma cases was observed. Targeted therapy with a BRAF V600E inhibitor such as vemurafenib may have potential in the treatment of lung cancer with this mutation; however, it is necessary to consider how the treatment effect of and drug resistance to BRAF V600E inhibitors are affected by the presence of heterogeneity in future studies. PMID- 26136883 TI - Complete recovery from paraneoplastic anti-NMDAR encephalitis associated with a small ovarian teratoma following a laparoscopic salpingo-oophorectomy: A case report. AB - Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a severe but treatment-responsive disorder, initially identified in young women with an ovarian teratoma. Symptoms include mood, behavior and personality irregularities that resemble acute psychosis. The present study reports the rare case of a patient with anti-NMDAR encephalitis and severe neurological symptoms, that exhibited a rapid recovery following a laparoscopic salpingo-oophorectomy. The 39 year-old woman was admitted to the Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine (Osaka, Japan) with a 5-day history of fever and stomach ache. One week later, the patient developed hallucinations and emotional lability. Initially, a diagnosis of limbic or herpes encephalitis was considered; thus, the patient was administered acyclovir and received steroid pulse therapy. However, the patient subsequently developed apnea, and in response, a tracheal intubation, mechanical ventilation and plasmapheresis were performed. Anti-NMDAR encephalitis was subsequently considered as a diagnosis and mediastinal and pelvic computed tomography (CT) examinations were conducted to detect for the presence of a teratoma. A 24*24-mm cystic lesion was identified in the pelvis from an abdominal CT scan and the lesion appeared to be an ovarian teratoma. In addition, serum and cerebrospinal fluid samples were collected, and were found to test positive for anti-NMDAR antibodies. A laparoscopic salpingo oophorectomy was performed, which resulted in rapid improvement of the patients mental symptoms, followed by a complete recovery. PMID- 26136884 TI - Unregulated long non-coding RNA-AK058003 promotes the proliferation, invasion and metastasis of breast cancer by regulating the expression levels of the gamma synuclein gene. AB - The aim of the present study was to investigate the function of long chain non coding RNA (lncRNA) in breast cancer cells. Quantitative polymerase chain reaction was used to measure mRNA expression levels in breast cancer tissues, adjacent tissues and in MCF-7 breast cancer cells. Western blot analysis was used to determine the protein expression levels. In addition, a 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium bromide assay was employed to measure the rates of cell proliferation. The invasion and migration of the MCF-7 cells were examined using a Transwell(r) assay. The expression levels of lncRNA-AK058003 were increased significantly in the breast cancer tissues and were found to strongly correlate with the severity of the breast cancer clinical stage. Bioinformatics analysis revealed that the gamma-synuclein gene (SNCG) may be a target gene regulated by lncRNA-AK058003. Thus, lncRNA-AK058803 was downregulated using small interfering RNA, and the mRNA and protein expression levels of SNCG were shown to be significantly reduced. Furthermore, the proliferation, invasion and migration rates of the MCF-7 breast cancer cells were significantly reduced. Therefore, the results demonstrated that unregulated lncRNA-AK058003 in breast cancer cells promotes cancer cell proliferation, invasion and metastasis via the regulation of SNCG expression. PMID- 26136885 TI - Study of the association between CD28/CTLA-4 expression and disease activity in juvenile idiopathic arthritis. AB - The aim of the present study was to investigate the immune function of children with juvenile idiopathic arthritis (JIA). Flow cytometry and three-color direct immunofluorescence were used to examine cluster of differentiation (CD)3+ T lymphocyte subsets and CD28/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in whole blood (using the no-wash method) from 36 children with JIA and 39 healthy children. During the active phase of JIA, CD28 expression on CD4+ T cells in children with JIA was significantly reduced; thus, CD4+CD28- T-cell frequency increased, suggesting that CD4+ T-cell and CD4+CD28- T-cell apoptosis was inhibited in patients with JIA. The continued survival of these immune-active T lymphocytes may promote the occurrence and development of JIA. CTLA-4 expression levels on CD4+ and CD8+ T cells in children with JIA during the active phase were significantly higher than those in normal controls. As the majority of CD4+ T cells in patients with JIA are CD28-, they cannot be inactivated by the interaction between CTLA-4 and B7, leading to continuously high levels of CTLA-4 expression on the surface of CD4+ T cells without functional effect. Hence, T lymphocytes are continuously kept in a highly activated state that is difficult to stop. During the resting phase, the CD4+ and CD8+ T-cell counts in children with JIA were similar to normal, and CD28 expression was also normal. This suggests that the frequency of CD4+CD28- T cells can be used as an indicator of the active phase of JIA. CTLA-4 expression on the surface of T cells in children with JIA during the resting phase was also similar to that in normal controls, suggesting that abnormal lymphocyte activation plays an important role in the active phase of JIA. PMID- 26136886 TI - Anti-inflammatory effect of 1,25-dihydroxyvitamin D3 is associated with crosstalk between signal transducer and activator of transcription 5 and the vitamin D receptor in human monocytes. AB - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has an anti-inflammatory effect on human monocytes incubated with sera from patients with type 2 diabetes/diabetic nephropathy; however, the detailed mechanism behind the effect remains to be explored. The current study further validated the effects of 1,25-(OH)2D3 and lipopolysaccharide (LPS) + human recombinant interleukin (IL)-15 on the expression of the vitamin D receptor (VDR) and phosphorylated signal transducer and activator of transcription 5 (p-STAT5) in human monocytes and explored the possible interaction between VDR and p-STAT5. Synchronized THP-1 cells were divided into pre-intervened groups, namely the control, LPS + IL-15 and 1,25 (OH)2D3, groups, according to their differing treatments. The expression of STAT5 and p-STAT5 was evaluated by western blot analysis; the concentration of IL-6 in the supernatant was determined using an enzyme-linked immunosorbent assay; the expression of cytoskeletal proteins was observed using immunofluorescence and laser confocal microscopy; and the possible intranuclear interaction between VDR and p-STAT5 was investigated using immunofluorescence, immuno-coprecipitation and western blot analysis. LPS + IL-15 upregulated p-STAT5 expression and the IL-6 level (P<0.05), with cytoskeletal rearrangement. These effects were partially prevented through pretreatment with 1,25-(OH)2D3. The LPS + IL-15 group and the 1,25-(OH)2D3 group exhibited an interaction between p-STAT5 and VDR in the nucleus, with the latter group showing a significant increase compared with the former (P<0.05). The immuno-coprecipitation results provided evidence of the interaction between VDR and p-STAT5, which suggests the existence of STAT5-VDR crosstalk in THP-1 monocytes. Cytoskeletal rearrangement, VDR and p-STAT5 potentially have interactions in THP-1 monocytes. The anti-inflammatory effect of 1,25-(OH)2D3 may be associated with crosstalk between STAT5 and VDR, which further induces cytoskeletal rearrangement. PMID- 26136888 TI - Cloning, expression and identification of an isoform of human stromal cell derived factor-1alpha. AB - Human stromal cell derived factor-1alpha (hSDF-1alpha), a chemotactic factor of stem cells, regulates inflammation, promotes the mobilization of stem cells and induces angiogenesis following ischemia. Six SDF-1 isoforms, SDF-1alpha, SDF 1beta, SDF-1gamma, SDF-1delta, SDF-1epsilon and SDF-1phi, which all contain a signal peptide at the N-terminus, have been reported. In the present study a special isoform of hSDF-1alpha is described that does not contain the N-terminal signal peptide sequence. The hSDF-1alpha gene was cloned with the recombinant plasmid pCMV-SPORT6-hSDF1 as the template, and the prokaryotic expression vector pET15b-hSDF-1alpha was constructed. This hSDF-1alpha was successfully expressed as an inclusion body in Escherichia coli BL21(DE3). The recombinant hSDF-1alpha was refolded in vitro and separated by cation exchange chromatography. Following these two steps the purity of the hSDF-1alpha was able to reach >85%. The recombinant hSDF-1alpha was then purified by size-exclusion chromatography. SDS PAGE analysis demonstrated that the purity of the hSDF-1alpha was >95%, which meets almost all the requirements of a protein experiment. Chemotactic activity of the recombinant hSDF-1alpha was analyzed by Transwell migration assay and it was found that the recombinant hSDF-1alpha was able to stimulate THP-1 cell migration. These data suggest that the procedure of producing recombinant hSDF 1alpha proteins with chemotactic activity was feasible and the N-terminal signal peptide of hSDF-1alpha has little effect on the chemotactic activity of hSDF 1alpha. PMID- 26136887 TI - Cardioprotective effect of remote preconditioning of trauma and remote ischemia preconditioning in a rat model of myocardial ischemia/reperfusion injury. AB - Remote ischemia preconditioning (RIPC) and remote preconditioning of trauma (RPCT) are two methods used to induce a cardioprotective function against ischemia/reperfusion injury (IRI). However, the underlying mechanisms of these two methods differ. The aim of the present study was to investigate the cardioprotective function of the two methods, and also observe whether combining RIPC with RPCT enhanced the protective effect. In total, 70 male Sprague Dawley rats were randomly divided into five groups, which included the sham, control, RIPC + RPCT, RPCT and RIPC groups. With the exception of the sham group, all the rats were subjected to myocardial IRI through the application of 30 min occlusion of the left coronary artery and 180 min reperfusion. Serum cardiac troponin I (cTnI) levels, myocardial infarct size (IS) and the cardiomyocyte apoptotic index (AI) were assessed. The levels of serum cTnI were lower in the experimental groups when compared with the control group (control, 58.59+/-12.50 pg/ml; RIPC + RPCT, 46.05+/-8.62 pg/ml; RPCT, 45.98+/-11.24 pg/ml; RIPC, 43.46+/-5.05 pg/ml; P<0.05, vs. control), and similar results were observed for the myocardial IS (control, 48.34+/-6.79%; RIPC + RPCT, 29.64+/-4.51%; RPCT, 29.05+/-8.51%; RIPC, 27.72+/-6.27%; P<0.05, vs. control) and the AI (control, 31.75+/-10.65%; RIPC + RPCT, 18.32+/-9.30%; RPCT, 18.51+/-9.26%; RIPC, 20.41+/-3.86%; P<0.05, vs. control). However, no statistically significant differences were observed among the three experimental groups (P>0.05). Therefore, RIPC and RPCT exhibit cardioprotective effects when used alone or in combination. However, a combination of RIPC and RPCT does not enhance the cardioprotective effect observed with the application of either single method. Therefore, for patients undergoing major abdominal surgery, RIPC was considered to be unnecessary, while for patients undergoing other types of non-cardiac major surgery and minimally invasive interventional surgery, RIPC may be useful. In addition, patients with embolism diseases are also liable to IRI when reperfusion treatment such as thrombolysis is conducted. Thus RIPC may also be beneficial for these patients. PMID- 26136889 TI - Ligustrazine reduces blood-brain barrier permeability in a rat model of focal cerebral ischemia and reperfusion. AB - Ligustrazine, also known as 2,3,5,6-tetramethylpyrazine (TMP), one of the major active compounds of Ligusticum wallichii Franchat., has been shown to reduce neuroinflammation and protect neurons during cerebral ischemia/reperfusion injury. However, whether it reduces blood-brain barrier (BBB) permeability during ischemic stroke is unclear. The aim of the present study was to investigate the role that TMP plays in protecting the BBB integrity in ischemia/reperfusion injury and to investigate the relevant mechanisms involved. Rats received an intraperitoneal injection of 20 mg/kg TMP 15 min before the onset of ischemia, which was induced by middle cerebral artery occlusion. Infarct volume, neurological score, brain edema, BBB permeability and tight junction protein impairment were observed. The results showed that TMP reduced the neurological score and levels of brain infarction and edema. In addition, TMP significantly decreased BBB permeability and prevented the impairment of occludin and claudin 5, two tight junction protein components of the BBB, in rat brains with ischemia/reperfusion injury. In addition, the expression and activity of matrix metalloproteinases, enzymes responsible for the degradation of the extracellular matrix and tight junctions, were reduced in the rat brains by TMP treatment. These results combined suggest that TMP reduces BBB permeability as well as neuronal damage in focal cerebral ischemia/reperfusion injury in rats. PMID- 26136890 TI - Analysis of the clinical and molecular characteristics of a child with achondroplasia: A case report. AB - Achondroplasia (ACH) is a hereditary dwarfism caused by the disturbed proliferation and differentiation of growth plate chondrocytes, followed by impaired endochondral bone growth. ACH is caused by mutations in the gene encoding the transmembrane receptor, fibroblast growth factor receptor 3 (FGFR3). In total, >90% of patients with ACH have a G1138A mutation in the transmembrane domain of the FGFR3 gene. Patients with ACH usually have no growth hormone (GH) deficiency. The current study presents the case of a four-year-old male with clinical manifestations suggestive of ACH, including a large head, prominent forehead, short upper arms and legs, and short hands with fingers assuming a trident position. The patient showed normal responses to GH provocation tests with L-dopa (peak GH concentration, 42.38 ng/ml) and insulin (peak GH concentration, 23.29 ng/ml during hypoglycemia), but a blunted response to a GH provocation test with arginine (peak GH concentration, 7.31 ng/ml). Furthermore, the GH concentration during exercise was low (4.8 ng/ml). Magnetic resonance imaging revealed a decreased pituitary volume. Thyroid function tests and the levels of sex hormones (follicle stimulating hormone, luteinizing hormone, estradiol, prolactin and progesterone), cortisol and adrenocorticotropic hormone were normal. A heterozygous G1138A mutation within the FGFR3 gene was detected, confirming the diagnosis of ACH. Thus, recombinant human GH therapy (0.1 IU/kg/day) was initiated. At the six-month follow-up, the height, arm span-to height ratio and lower limb length-to-height ratio of the patient had increased, while the head circumference had decreased. The present results corroborate the finding that the G1138A mutation within FGFR3 is the most common ACH-causing mutation in different populations. GH may be beneficial in the treatment of short stature in ACH patients with subnormal GH secretion. PMID- 26136891 TI - Neuroprotective effect of paeoniflorin on H2O2-induced apoptosis in PC12 cells by modulation of reactive oxygen species and the inflammatory response. AB - Paeoniflorin (PF) is a product derived from Paeoniae Radix and is commonly prescribed in traditional Chinese medicine. PF has been reported to exhibit neuroprotective, anti-ischemic, antioxidant, anti-inflammatory and anticancer effects. The neuroprotective properties of PF have been demonstrated in animal models of various neuropathologies. The present study investigated the effects of PF on hydrogen peroxide (H2O2)-induced apoptosis in PC12 cells, to improve the understanding of the mechanisms underlying its neuroprotective properties. The H2O2-induced apoptosis of PC12 cells resulted in a reduction in the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein ratio and the activation of caspase 3. PF treatment was observed to reverse the apoptotic process and to modulate the expression levels of a number of apoptosis-associated proteins. Furthermore, PF significantly mitigated the H2O2-induced reduction in cell viability, in addition to scavenging reactive oxygen species and preventing the release of lactate dehydrogenase from the PC12 cells. In addition, the apoptosis-associated activation of nuclear factor (NF)-kappaB was inhibited in the PF-treated cells, and the expression levels of tumor necrosis factor alpha and interleukin (IL) 1beta were reduced. In conclusion, the present study demonstrated that PF was able to reduce H2O2-induced toxicity by blocking the activation of the neuroinflammatory factor NF-kappaB. These results suggest that PF may be a valuable neuroprotective agent for the treatment of neurological disease and injury. PMID- 26136892 TI - Fructus Corni extract-induced neuritogenesis in PC12 cells is associated with the suppression of stromal interaction molecule 1 expression and inhibition of Ca2+ influx. AB - Fructus Corni (Cornus officinalis Sieb. et Zucc.) is commonly prescribed as a traditional Chinese herbal medicine that possesses pharmacological actions against inflammation, diabetic nephropathy, tumors, oxidation and aging. However, its function and mode of action within the nervous system remain largely unclear. In this study, the effects of Fructus Corni extract (FCE) on neuronal differentiation were investigated. It was found that FCE significantly increased the percentage of PC12 cells bearing neurites (P<0.001). Following the generation of neurite outgrowth, FCE treatment decreased the mRNA expression of stromal interaction molecule 1 (STIM1; P<0.05) and suppressed the expression of STIM1 protein (P<0.001). In addition, extracellular calcium (Ca2+) influx was inhibited resulting in a reduction in the intracellular Ca2+ level, suggesting that the inhibition of Ca2+ influx may be involved in the FCE-promoted neurite outgrowth of PC12 cells. These results demonstrate that FCE induces neurite outgrowth in PC12 cells and that this is associated with the suppression of STIM1 expression and the inhibition of Ca2+ influx, which may partially explain the FCE-induced neuritogenesis. PMID- 26136893 TI - Effect of Polycalcium, a mixture of Polycan and calcium lactate-gluconate in a 1:9 weight ratio, on rats with surgery-induced osteoarthritis. AB - In the present study, the beneficial and synergistic effects of Polycalcium, a mixture of Polycan and calcium (Ca) lactate-gluconate in a 1:9 weight ratio, on a rat model of osteoarthritis (OA) were explored. Polycalcium (50, 100 and 200 mg/kg) was administered orally once per day for 28 days from 1 week after the OA modeling surgery. Diclofenac sodium (2 mg/kg) was administered as a reference drug. Following the OA surgery, increases in the maximum extension angles, edematous changes in knee and capsule thickness, reductions in chondrocyte proliferation and cartilage glycosaminoglycan (GAG) levels, as well as changes in cartilage degeneration were observed. However, these OA-related symptoms were inhibited after 28 days of continuous oral treatment with Polycalcium. Anti-OA effects, including the induction of chondrocyte proliferation, were detected in the Polycalcium-treated rats and were more favorable compared with those in rats treated with Polycan or Ca lactate-gluconate alone (100 mg). Therefore, a mixture of Polycan and Ca lactate-gluconate was demonstrated to have beneficial synergistic effects on OA. PMID- 26136894 TI - Antiproliferative effect of the methanol extract from the roots of Petasites japonicus on Hep3B hepatocellular carcinoma cells in vitro and in vivo. AB - Traditional medicinal plants have been used in the treatment of various diseases for centuries. A number of plant-derived compounds have been proposed as anticancer agents and are currently undergoing medical development. Petasites japonicus (PJ), also known as Butterbur, is a herb cultivated in East Asia that is used as a traditional herbal medicine. The aim of the present study was to investigate whether a methanol extract of PJ demonstrated anticancer activity against Hep3B hepatocellular carcinoma (HCC) cells. The anticancer property and underlying mechanism of the extract were evaluated by assessing the effect on cell viability, nuclear morphology and the expression of phosphorylated (p)-mTOR, p-Akt, beta-catenin and p-glycogen synthase kinase-3beta, which are markers for cancer cell proliferation and metastasis. These results were obtained by the MTT assay, fluorescence microscopy and Western blot analysis. The methanol extract of PJ was shown to decrease the cell viability in a concentration-dependent manner. In addition, the methanol extract of PJ was found to inhibit the growth of Hep3B HCC cells through inhibiting the Akt/mTOR and Wnt signaling pathways. These results suggest that the methanol extract of PJ exerts an anticancer effect on Hep3B HCC cells. PMID- 26136895 TI - Reductions in calcitonin gene-related peptide may be associated with the impairment of the contralateral testis in unilateral cryptorchidism. AB - The aim of the present study was to investigate the mechanism underlying the impairment of the contralateral testis in unilateral cryptorchidism in experimental rats using a molecular neurophysiological approach. Thirty-six male rats (21 days old) were divided into a cryptorchidism group, a cryptorchidism with division of the genitofemoral nerve (GFN) group and a control group (n=12/group). The distribution of the calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers in the testes was studied using an immunohistochemistry technique. Germ cell apoptosis was detected using the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling method. The concentration of malondialdehyde (MDA) in the testis tissue was evaluated using a spectrophotometric determination method, and the ultrastructure of Sertoli cells was observed using transmission electron microscopy. It was found that, 100 days after the surgery, the concentration of CGRP in the cryptorchidism group was decreased significantly, whereas the levels of MDA and the number of apoptotic germ cells were increased significantly compared with the control group (P<0.01). Following the division of the GFN, the damaging effects were decreased (P<0.01). The impairment mechanism may therefore be associated with a reduction in the level of CGRP in the contralateral testis. The reflex decrease in CGRP may be caused by germ cell apoptosis, decreased blood flow and oxygen levels, and the increase in reactive oxygen free radicals and lipid peroxidation. PMID- 26136896 TI - Hypoxia-inducible factor-1alpha antagonizes the hypoxia-mediated osteoblast cell viability reduction by inhibiting apoptosis. AB - Bone fracture is accompanied with poor oxygen supply and nutrient deficiency in the local fracture site, and oxygen supply is an important factor that can affect fracture healing. Hypoxia-inducible factor-1 (HIF-1) plays a key role in the regulation of oxygen homeostasis. HIF-1alpha is rapidly upregulated in response to hypoxia and antagonizes hypoxia-induced apoptosis. In the present study, the viability of an osteoblast cell line, MC3T3-E1, and the expression of HIF-1alpha protein in the MC3T3-E1 cells was examined under hypoxic conditions. The HIF 1alpha level was then manipulated and the reduction in the viability of the MC3T3 E1 cells in response to the hypoxia was re-evaluated. In addition, the regulation of HIF-1alpha in the adaptation of MC3T3-E1 cells to hypoxia was explored. The results showed that the viability of MC3T3-E1 cells decreased and the expression of HIF-1alpha protein increased under hypoxic conditions. Furthermore, the reduction in the viability of MC3T3-E1 cells post-hypoxia was attenuated by HIF 1alpha overexpression, while HIF-1alpha-knockdown by small interfering RNA enhanced the hypoxia-induced decrease in cell viability. It was additionally found that the forced expression of HIF-1alpha inhibited the hypoxia-induced cell apoptosis. These findings indicate that the forced expression of HIF-1alpha inhibits hypoxia-induced apoptosis and thus attenuates the hypoxia-induced decrease in cell viability. PMID- 26136897 TI - Chest wall tumors: Diagnosis, treatment and reconstruction. AB - The aim of the present study was to determine a suitable procedure for the treatment of chest wall neoplasms with less potential risk and an increased rate of survival. Fifty patients with suspected chest wall malignancies were analyzed using various preliminary investigation tools. Whole-chest scanning was performed in all the patients. The patients were subsequently subjected to biopsies for further confirmation of the neoplasm. All such patients were then treated with a surgical approach and radiation therapy, with a follow-up period lasting up to six years. The majority of the patients showed improved survival rates relative to conventional therapies. The survival rates of patients suffering from osteosarcoma (78%) were higher those of patients with rhabdomyosarcoma (73%) and malignant small round cell tumors (64%). The survival and the mortality rates of the patients with synovial sarcoma and fibrosarcoma were the same. This study, which was conducted on a small group of patients, has provided guidance for further studies on tumors of the chest wall, which may, in turn, increase the longevity of affected patients. PMID- 26136898 TI - Effect of the non-specific matrix metalloproteinase inhibitor Doxycycline on endometriotic implants in an experimental rat model. AB - The aim of this study was to investigate the possible therapeutic effects of Doxycycline (Dox) on endometriotic lesions in an experimental rat model. Thirty seven female Wistar albino rats with surgically induced endometriosis were randomized and divided into four groups. The rats were administered 5 mg/kg/day oral Dox in Group 1 (low-dose Dox group, n=9), 20 mg/kg/day oral Dox in Group 2 (high-dose Dox group, n=10) and 1 mg/kg single dose, subcutaneous leuprolide acetate in Group 3 (leuprolide acetate group, n=9). The rats in Group 4 (control group, n=9) were given no medication. The rats received medication for three weeks and were then sacrificed to evaluate the morphological and histological features of the implants. Matrix metalloproteinase (MMP)-9 immunoreactivity of the implants was also evaluated. The size of the endometriotic implants decreased in Groups 1-3 but statistically significant differences were not observed among the groups. The mean surface area of the endometriotic implants decreased from 69.3+/-30.8 to 52.1+/-27.0 mm2 in Group 1 (P>0.05), from 60.2+/-18.9 to 38.6+/ 28.7 mm2 in Group 2 (P>0.05) and from 58.1+/-33.1 to 26+/-9.0 mm2 in Group 3 (P=0.03). The epithelial MMP-9 immunohistochemical score was significantly higher in Group 1 and lower in Group 3 when compared with the control group (Group 4) (P=0.042 and P=0.014, respectively). When the stromal MMP-9 immunohistochemical and histopathological scores of the endometriotic implants were compared, no statistically significant differences were found among the groups. Although there was no statistically significant difference, Dox reduced the endometriotic implant area in the rat endometriosis model. Further studies are required to investigate the potential efficacy of Dox in endometriosis due to its widespread use and tolerability. PMID- 26136899 TI - Humulus japonicus extract exhibits antioxidative and anti-aging effects via modulation of the AMPK-SIRT1 pathway. AB - The perennial herb, Humulus japonicus, has been previously described as possessing potential antituberculosis and anti-inflammatory properties. In the present study, the anti-aging activity of ethanol extracts from the leaves of H. japonicus (HJE) was evaluated in yeast and human fibroblast cells. In addition, the antioxidant activity of HJE was analyzed using free radical scavenging assays. Furthermore, the mechanism underlying the hypothesized HJE-associated extension of lifespan was investigated, and the results indicated that HJE was able to extend the lifespan of yeast cells. Further experiments demonstrated that HJE upregulated the longevity-associated proteins, sirtuin 1 and AMP-activated protein kinase, and effectively inhibited the generation of reactive oxygen species (ROS). In addition, the antioxidative potential of the active constituents of HJE, including luteolin, luteolin 7-glycoside, quercetin and quercitrin, was evaluated and the results demonstrated that these flavonoids were able to scavenge ROS in cell-free and intracellular systems. In summary, the results revealed that HJE possessed the potential for antioxidative activity; however, further in vivo investigations are required with the aim of developing safe, high-efficacy anti-aging agents. PMID- 26136900 TI - Metabolic regulation of magnolol on the nuclear receptor, liver X receptor. AB - The aim of the present study was to investigate whether magnolol, the essential component of the traditional Chinese medicine, Magnolia officinalis, can pass through liver X receptor alpha (LXRalpha), to subsequently play an important role in the lipid metabolic balance. Using a HepG2 human hepatoma cell line, mammalian cellular one-hybridization and mammalian cell transcriptional activation experiments were performed to detect the combination degree of magnolol at different concentrations with LXRalpha, and assess the transcriptional activity. In addition, using a THP-1 human monocytic cell line, quantitative polymerase chain reaction was performed to assess the effect on the expression levels of downstream genes. Magnolol was shown to dose-dependently combine with LXRalpha, and subsequently regulate the transcriptional activity of LXRalpha. In addition, magnolol was found to adjust the expression of associated LXRalpha downstream genes in the macrophages. In conclusion, magnolol was demonstrated to affect LXRalpha, which may outline a new molecular mechanism through which magnolol exerts a lipid-lowering function. PMID- 26136902 TI - Association between coffee consumption and serum lipid profile. AB - The aim of the present study was to investigate the association between coffee consumption and serum lipid levels in a study population of 122 Turkish subjects (mean age, 41.4+/-12.69 years), including 48 males and 74 females. A questionnaire was compiled to determine baseline characteristics, and food and coffee consumption. Subjects were divided into three groups, which included non drinkers, Turkish coffee and instant coffee drinkers, and anthropometric measurements were acquired, including weight, height and body mass index. Serum lipid levels were analyzed, including the total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels. Of the population studied, 76.2% had consumed at least one cup of coffee per week over the previous year. Daily consumption values were 62.3+/-40.60 ml (0.7+/-0.50 cup) for Turkish coffee and 116.3+/-121.96 ml (0.7+/-0.81 cup) for instant coffee. No statistically significant differences were observed in the serum levels of TC, TG, LDL-C, HDL-C or VLDL-C among the three groups. In addition, no statistically significant differences were observed in the serum lipid levels when comparing individuals who consumed coffee with sugar/cream or who smoked and those who did not (P>0.05). Therefore, the present observations indicated no significant association between the consumption of Turkish or instant coffee and serum lipid levels. PMID- 26136903 TI - Effects of recombinant human thyroid stimulating hormone on 131I therapy for the treatment of differentiated thyroid cancer. AB - The aim of the present study was to compare the advantages and disadvantages of the combined application of recombinant human thyroid stimulating hormone (rhTSH) with thyroid hormone withdrawal (THW) and THW alone prior to 131I therapy for the treatment of differentiated thyroid cancer. Four indicators were compared between the experimental group, who received a combined therapeutic method of rhTSH with THW, and the control group, who received THW therapy alone. With the exception of the elimination half-time of 131I in the blood in the experimental group, which was significantly shorter compared with that in the control group, the other three indicators, including the urinary iodine concentration, the relative 131I uptake ratio of the neck lesions and the one-time cure rate, were not significantly different between the two groups. In addition, the treatment efficacy of 131I therapy exhibited no statistically significant difference between the experimental and control groups. However, in the experimental group, the residence time of 131I in the blood was significantly shorter compared with that in the control group, indicating that the irradiation damage of radioactive iodine exposure to the non-target tissues was lower in the experimental group when compared with the control group. In addition, no evident hypothyroidism was observed in the patients. Thus, the combined application of rhTSH with THW prior to 131I therapy was demonstrated to be superior to the THW therapy alone. PMID- 26136901 TI - Association of BDNF and BCHE with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls. AB - Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with beta-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08-3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date. PMID- 26136904 TI - Afatinib inhibits proliferation and invasion and promotes apoptosis of the T24 bladder cancer cell line. AB - Afatinib is a highly selective, irreversible inhibitor of the epidermal growth factor receptor (EGFR) and human EGFR 2 (HER-2). Although preclinical and clinical studies have indicated that afatinib has antitumor activity and clinical efficacy in non-small cell lung carcinoma, head and neck squamous cell carcinoma and breast cancer, there are few studies investigating its inhibitory effect on human bladder carcinoma cells. In this study, the antitumor effect of afatinib was investigated on the T24 bladder cancer cell line. The T24 bladder cancer cell line was treated with afatinib at various concentrations (0, 1, 5, 10 and 20 umol/l). MTT assay was used to estimate the proliferation of the T24 cells; flow cytometric analysis was used to estimate the effect of afatinib on T24 cell apoptosis; cell invasion ability was assessed by a Transwell invasion assay; and western blot analysis was used to detect the expression of Bcl-2, Bax, Akt, extracellular-signal-regulated kinase (ERK)1/2, matrix metalloproteinase (MMP)-2 and MMP-9. The MTT assay demonstrated that afatinib inhibited the proliferation of T24 cells in a dose- and time-dependent manner. Flow cytometric analysis revealed that the cell apoptosis rate increased as the concentration of afatinib increased. The cell invasion assay indicated that afatinib treatment significantly inhibited the invasive behavior of T24 cells in a dose-dependent manner. Western blot analysis showed that with increasing afatinib concentrations, Bcl-2, phosphorylated (p)-ERK1/2, p-Akt, MMP-2 and MMP-9 expression levels were significantly decreased, whereas total (t)-ERK1/2 and t Akt expression levels remained basically unchanged, and Bax expression levels were greatly increased. The results indicate that afatinib inhibits the proliferation and invasion of T24 cells in vitro and induces the apoptosis of these cells by inhibiting the EGFR signaling network. PMID- 26136905 TI - Limitations of Gram staining for the diagnosis of infections following total hip or knee arthroplasty. AB - The diagnosis of prosthetic joint infection (PJI) following total joint arthroplasty is difficult for clinicians to make decisions due to the similar symptoms presented by aseptic loosening and infection. Gram staining (GS) is a widely used test but its value remains controversial due to conflicting results in the diagnosis of PJI. The aim of the present study was therefore to evaluate the value of GS in the diagnosis of PJI. Searches using MEDLINE, EMBASE and OVID databases were conducted for data published between January 1990 and December 2013. Meta-analysis was used to pool the sensitivity, specificity, diagnostic odd ratios (DORs), area under the receiver-operating characteristic curve (AUC), positive-likelihood ratios (PLRs), negative-likelihood ratios (NLRs) and post test probability. The heterogeneity and publication bias were assessed, and subgroup and meta-regression analyses were conducted. A total of 18 studies, including a total of 4,647 patients, were selected for analysis. The pooled sensitivity and specificity values for the diagnosis of PJI were 0.19 and 1.00, respectively. The AUC, PLR and NLR were 0.89, 41.6 and 0.82, respectively. Subgroup analyses indicated that the sensitivity/specificity for total hip arthroplasty was 0.14/0.99, whereas that for total knee arthroplasty was 0.14/1.00. Synovial fluid best reflected accurate GS-based diagnoses, with the highest DOR of 242, whereas tissue had the highest AUC of 0.96 (95% CI, 0.94 0.97). GS had a poor clinically acceptable diagnostic value for detecting PJI. These data do not support the routine use of GS, without additional proof of infection, for diagnosing PJI; instead, GS could be used as an adjuvant tool to support the results of other investigations. PMID- 26136906 TI - Protocatechuic acid benefits proliferation and phenotypic maintenance of rabbit articular chondrocytes: An in vitro study. AB - Numerous antioxidants exhibit antiarthritic effects due to their inhibitory effect on inflammatory factors. Certain antioxidants, such as protocatechuic acid (PCA) and its analogs, have been reported to be effective in the treatment of arthritis. However, the effect of PCA on chondro-protection may be alleviated due to the induction of apoptosis, as has been demonstrated in stomatocytes. To clearly determine the effect of PCA on the biological and cellular metabolism of rabbit articular chondrocytes in vitro, examinations of cytotoxicity, proliferation and morphology were performed, in addition to analyses of glycosaminoglycan (GAG) synthesis and the expression of cartilage-specific genes. The results revealed that PCA effectively promoted chondrocyte growth, the synthesis of the extracellular matrix and the mRNA expression of aggrecan, collagen II and Sox9, while downregulating the expression of the collagen I gene, a marker of chondrocyte dedifferentiation. In addition, hypertrophy, which may result in chondrocyte ossification, was not detected in the groups. Among the doses (range, 0.05-0.3 mmol/l) of PCA that promoted the proliferation of chondrocytes, a concentration of 0.125 mmol/l produced the optimum performance. The results indicated that PCA, particularly at a dose of 0.125 mmol/l, accelerated the proliferation of rabbit articular chondrocytes in vitro and maintained their phenotype. This study may provide a basis for further research concerning the treatment of cartilage defects. PMID- 26136907 TI - Clinical analysis of a patient with a benign lesion of the pharynx misdiagnosed as functional thyroid cancer metastasis. AB - Papillary thyroid carcinoma (PTC) usually has a lower malignancy rate and better prognosis than other types of thyroid cancer. It tends to spread through the lymphatic system, and the percentage of lymph node metastasis to the neck is 50 70% in patients at the time of diagnosis. Iodine-131 (131I) whole-body scanning is very valuable in the diagnosis and positioning of functional metastatic lesions. However, a variety of comprehensive test results are frequently required to make an appropriate judgment. The present case report describes the case of a patient with PTC where a benign lesion of the pharynx was misdiagnosed as functional metastasis. Some remnant thyroid tissue and an abnormal accumulation of 131I in the oropharynx and at the right side of the neck were observed by 131I whole-body scanning one week after the first therapeutic dose. Following the second therapeutic dose, quasi-circular trapping of 131I by the pharynx persisted. Magnetic resonance imaging enhanced scanning of the oropharynx showed markedly uneven enhancement inside the lesion, and it was considered as a metastatic lesion. However, the serological test results of the patient revealed that there was no increase in the thyroglobulin level and did not support the diagnosis of progressive disease. Therefore, a biopsy on the lesion was conducted under local anesthesia. The histopathological examination exhibited salivary gland tissue and chronic inflammation. Thus, it was necessary to analyze the imaging results, as well as serologic testing outcomes and pathological findings comprehensively, in order to make the correct diagnosis. PMID- 26136908 TI - Clinical potential of resistin as a novel prognostic biomarker for cellulitis. AB - Cellulitis is an acute, subacute or chronic inflammation of the dermis and subdermal tissues, which is typically caused by bacteria, although other causes are possible. The present study aimed to evaluate the association between resistin levels and the recovery time of patients with cellulitis. In addition, the effect of resistin and insulin resistance on the prognosis of cellulitis was investigated. In total, 52 patients with cellulitis (male, 21; female, 31) and an age-matched group of 42 healthy individuals (male, 18; female, 24) were included in the study. The levels of serum resistin, fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR), C-reactive protein (CRP) and other biochemical parameters were compared between the groups. The mean resistin levels in the cellulitis and control groups were 9.4+/-5.3 and 5.8+/-3.1 ng/ml, respectively. The levels of resistin, FPG, HOMA-IR and CRP were significantly higher in the cellulitis group compared with the control group (P<0.001). Furthermore, the mean recovery time of the patients with cellulitis was 21.2+/-5.6 days. Thus, increased levels of resistin (P=0.002) and HOMA-IR (P=0.005) could be used as predictive factors for the recovery time. The enhanced levels of resistin and HOMA-IR were shown to correlate with the high CRP levels in the cellulitis group. Therefore, the results indicated that increased levels of resistin may function as a prognostic marker for cellulitis. PMID- 26136909 TI - Small interfering RNA-induced inhibition of epithelial cell transforming sequence 2 suppresses the proliferation, migration and invasion of osteosarcoma cells. AB - Osteosarcoma (OS) is the most common malignant tumor in bones. Although the five year survival rate has improved to ~60% for patients without metastasis, the prognosis remains poor for patients with metastatic OS. Epithelial cell transforming sequence 2 (ECT2) has been shown to act as an oncogene in human malignancies. More recently, ETC2 was shown to be involved in the development and progression of OS; however, the detailed role of ECT2 in the regulation of cellular biological processes in OS cells remains largely unknown. Therefore, it was investigated in the present study. It was found that the expression of ECT2 was notably increased in OS tissues when compared with that in matched normal adjacent tissues. Furthermore, it was established that the downregulation of ECT2 induced by transfection with ECT2-specific small interfering RNA effectively inhibited OS cell proliferation and induced cell apoptosis. Further investigation revealed that the inhibition of ECT2 expression suppressed OS cell migration and invasion, indicating that the overexpression of ECT2 promotes OS cell migration and invasion, while. In addition, western blotting results indicated that matrix metalloproteinases 2 and 9 may be involved in the ECT2-mediated OS cell invasion. In conclusion, the current study suggested that ECT2 acted as an oncogene in OS, and it may become a promising therapeutic target for the prevention and treatment of OS. PMID- 26136910 TI - Therapeutic efficacy of chlorogenic acid on cadmium-induced oxidative neuropathy in a murine model. AB - The aim of the present study was to determine whether chlorogenic acid (CA) is able to modulate cadmium (Cd)-induced oxidative brain damage. Cd-treated rats displayed numerous pathological effects, including the inhibition of acetylcholinesterase, elevated lipid peroxidation, the depletion of enzymatic and non-enzymatic antioxidants, the reduction of membrane-bound ATPase activity, mitochondrial dysfunction and DNA fragmentation. Pretreatment of the rats with CA significantly attenuated these effects. These results lead to the hypothesis that the mechanisms by which CA attenuates the effects of Cd-induced oxidative brain damage include the maintenance of antioxidant homeostasis, inhibition of the membrane effects and the perpetuation of mitochondrial dysfunction. These data support the potential of CA as a beneficial intervention in the prevention of heavy metal poisoning due to Cd exposure. PMID- 26136911 TI - Clinical characteristics of a group of patients with multiple myeloma who had two different lambda light chains by immunofixation electrophoresis: A retrospective study from a single center. AB - The objective of the present study was to conduct a retrospective analysis of the clinical characteristics of a group of patients with multiple myeloma (MM) who had two different immunoglobulin lambda light chains as determined by immunofixation electrophoresis (IFE). A total of 26 patients with MM had two different lambda light chains by IFE at diagnosis in hospital from January 2006 to June 2012. Data were collected from the medical records of these patients. The clinical characteristics, laboratory parameters, responses, risk factors and outcomes of this special group of patients were retrospectively analyzed. The patients with MM and two different lambda light chains by IFE accounted for 5.4% (26/483) of all the patients with MM during the same period. There were 17 patients (65.4%) with renal dysfunction and 10 patients (38.5%) with extramedullary plasmacytoma (EMP) at diagnosis. Ten patients (38.5%) had abnormalities by fluorescence in situ hybridization (FISH) including t(4;14), t(14;16) and/or del17p. Of these patients, three (11.5%) achieved complete remission (CR), six (23.1%) very good partial remission (VGPR), six (23.1%) partial remission (PR) and the overall remission (OR) rate was 57.7% (15/26). The OR rate of the patients who received chemotherapy with bortezomib was superior to that of the patients who received chemotherapy without bortezomib (78.6% vs. 33.3%; P<0.05). The OR rate of the patients who received autologous stem cell transplantation (SCT) was superior to that of the patients who did not receive autologous SCT (77.8% vs. 47.1%; P<0.05). The median overall survival (OS) was 12.6 months (range, 2-38 months) in this study. The patients who received chemotherapy with bortezomib had a significantly longer median OS as compared with the patients who received chemotherapy without bortezomib (19 vs. 6 months; P=0.049). The patients who received autologous SCT also had significantly longer median OS as compared with the patients who did not receive autologous SCT (18 vs. 7 months; P=0.041). The median duration of remission (DOR) was 5 months (range, 0-28 months). The patients who received bortezomib or autologous SCT had significantly longer median DOR than those who did not (P=0.046 and P=0.012, respectively). The patients with abnormalities by FISH had similar OR rates, median OS and median DOR as compared with the patients without abnormalities by FISH and there was no statistically significant difference in OR rate, median OS and median DOR between the patients with EMP and those without. The MM patients with two different lambda light chains by IFE may have specific characteristics, and are accompanied by a high incidence of renal dysfunction and EMP. They have a poor prognosis and require novel therapy including bortezomib and autologous SCT. PMID- 26136912 TI - Plasma concentrations of adrenomedullin and natriuretic peptides in patients with essential hypertension. AB - This study was designed to assess any changes in the plasma concentrations of adrenomedullin (ADM) and atrial and brain natriuretic peptide (ANP and BNP, respectively), and to investigate their pathophysiological roles in patients with essential hypertension (EH). The plasma ADM, ANP and BNP concentrations were measured in 64 patients with untreated EH and 35 normotensive control subjects. After 4 weeks of effective antihypertensive therapy with oral drugs for the hypertensive patients, the plasma concentrations of ADM, ANP and BNP in the hypertensive patients were measured again. The plasma concentrations of ADM, ANP and BNP were significantly higher in the hypertensive patients than those in the control subjects, and the concentrations increased with the clinical stage. Furthermore, the hypertensive patients exhibited increased mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr) and decreased glomerular filtration rates (GFRs) compared with the control subjects. The plasma ADM concentration was not only correlated with BUN, Scr and the GFR, but was also associated with the MAP and the plasma levels of ANP and BNP. Following effective antihypertensive therapy with oral medication for 4 weeks, the plasma concentrations of ADM, ANP and BNP were significantly, but not sharply, decreased. In conclusion, ADM, along with ANP and BNP, may be involved in the mechanisms acting against a further increase in blood pressure and may be useful biomarkers for the diagnosis and treatment of hypertensive patients. PMID- 26136913 TI - Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas. AB - Ghrelin, as a brain-gut peptide, has growth hormone (GH)-releasing and appetite inducing activities and a widespread tissue distribution. Furthermore, ghrelin is an endogenous ligand of the GH secretagogue receptor (GHSR), and both ghrelin and GHSR are expressed in the pituitary; however, the data regarding the expression of ghrelin and GHSR in pituitary adenomas are divergent and conflicting. In the present study, therefore, the expression of ghrelin and GHSR was examined in the full spectrum of human pituitary adenoma subtypes (n=34) and in normal pituitary tissue (n=3). The mRNA and protein expression levels were quantified using a competitive reverse transcription-polymerase chain reaction and western blotting and the correlation of the results with the clinical parameters was assessed. mRNA and protein expression of ghrelin and GHSR was detected in all samples with the highest mean level in GH adenomas, a moderate level in clinically non functioning adenomas and the lowest level in adrenocorticotropin adenomas. A significant correlation between the ghrelin and GHSR mRNA expression levels was observed in the GH adenomas (n=12) (r=0.8435, P=0.0006). The ghrelin mRNA expression level in the GH adenomas correlated positively with the basic serum GH level (n=12) (r=0.6488, P=0.0225). Furthermore, the mean level of ghrelin mRNA expression was significantly higher in invasive adenomas than in noninvasive adenomas (P<0.01). Collectively, the results of the study provided evidence that ghrelin and GHSR are expressed in the various subtypes of pituitary adenoma, with specific overexpression in GH adenomas. The study suggests that the binding of ghrelin to GHSR promotes the secretion of GH and plays an important role in the development of GH adenomas via autocrine and/or paracrine effects. PMID- 26136914 TI - Methylene blue treatment for cytokine release syndrome-associated vasoplegia following a renal transplant with rATG infusion: A case report and literature review. AB - Rabbit anti-thymocyte globulin (rATG) is an infusion of polyclonal rabbit-derived antibodies against human thymocyte markers, which can be used to prevent and treat acute rejection following organ transplantation. However, the product monograph issued by the manufacturer (Sanofi Canada) reports that serious immune mediated reactions have been observed following the use of rATG, consisting of anaphylaxis or severe cytokine release syndrome (CRS), which is a form of vasoplegic syndrome (VS), in which distributive shock occurs refractory to norepinephrine (NE) and vasopressin (VP). Severe infusion-associated reactions are consistent with CRS and can cause serious cardiac or respiratory problems, or in certain cases, mortality. CRS is a form of systemic inflammatory response syndrome (SIRS). In SIRS, the substantial activation of endothelial inducible nitric oxide synthase (iNOS) and smooth muscle guanylate cyclase (GC) is observed, which can produce severe hypotension that is unresponsive to conventional vasopressors. Methylene blue (MB) is a direct inhibitor of iNOS and GC and has been used as an effective treatment for VS following cardiothoracic surgery. In the present study, the successful use of MB as a rescue therapy for CRS in a patient receiving rATG following a renal transplant was reported. Following an uneventful cadaveric kidney transplant involving the intravenous (IV) administration of rATG for the induction of immunological tolerance, the patient became markedly hypotensive and tachycardic. The patient required high doses of VP and NE infusions. Following the protocol described for treating refractory VS in post-cardiac surgery patients, the decision was made to initiate the patient on an IV MB infusion. This treatment protocol was shown to improve the hemodynamic status of the patient, which enabled the withdrawal of vasopressors and suggests an important role for methylene blue in the management of refractory VS. PMID- 26136915 TI - Molecular and immunohistochemical effects of metformin in a rat model of type 2 diabetes mellitus. AB - Type 2 diabetes mellitus (T2DM) is a serious health issue worldwide. The disease is characterized by insulin resistance (IR), which leads to dyslipidemia and alterations in the expression levels of a number of genes. Metformin is the standard treatment for T2DM; however, the exact mechanism underlying metformin regulation is not fully understood. The aim of the present study was to investigate the effects of metformin on serum lipid profiles and the expression levels of various genes that are associated with IR, as well as the histopathological changes in the liver and pancreas. A T2DM rat model was established by feeding the rats a high-fat diet for 4 weeks, combined with a dose of streptozotocin (35 mg/kg body weight). Following the successful induction of T2DM, metformin was administered orally (400 mg/kg/day) for 4 weeks. The results indicated that metformin improved the symptoms of IR by normalizing the serum lipid profiles in the diabetic rats. Furthermore, metformin upregulated the expression of insulin receptors and genes associated with lipid metabolism, including acyl-CoA oxidase, carnitine palmitoyl transferase-1 and peroxisome proliferator activated receptor-alpha. In addition, treatment with metformin downregulated the expression levels of fetuin-A and retinol binding protein-4 (RBP-4), while normalizing the expression of perilipin that had been reduced in the T2DM rats. Metformin administration induced regenerative changes in the hepatocyte cytoplasm and parenchyma. In the pancreas, treatment with metformin was shown to induce positive signaling for insulin and the regeneration of pancreatic beta cells. In summary, metformin treatment ameliorated a number of the harmful effects associated with T2DM via the modulation of the expression levels of fetuin-A, RBP-4, perilipin and various genes associated with lipid metabolism, resulting in regenerative changes in the liver and pancreatic cells. PMID- 26136916 TI - Fahr's disease in two siblings in a family: A case report. AB - Idiopathic basal ganglia calcification, also known as Fahr's disease, is a rare neurological disease characterized by basal ganglia calcification, Parkinsonism and psychiatric symptoms. The majority of patients with Fahr's disease are adults. The present study describes the cases of two patients with Fahr's disease. The patients were brother and sister and their parents were close relatives. The onset age of Fahr's disease in these two patients was early, with the onset age of the brother being in the teens and the sister in early childhood. The patients exhibited different clinical manifestations. The main symptoms of the male patient were Parkinson's disease appearance and the loss of the ability to carry out simple calculations, while the main symptoms of the female patient were grand mal seizures and cerebellar ataxia. Although the two patients had distinct clinical manifestations, they both had similar intracranial multiple calcifications. The computed tomography scan remains the main method used in the diagnosis of Fahr's disease. Following treatment with dopamine and a dopamine receptor agonist, the extra-pyramidal symptoms of the male were significantly relieved. The female patient was administered antiepileptic drugs and there was no recurrence of epilepsy following treatment. PMID- 26136917 TI - Treatment with incomplete Freund's adjuvant and Listeria monocytogenes delays diabetes via an interleukin-17-secretion-independent pathway. AB - Non-obese diabetes (NOD) mice are widely used as an animal model in studies of type I diabetes (TID). Treatment with complete Freund's adjuvant (CFA) in pro diabetic NOD mice is known to inhibit disease progression by activating CD1d specific natural killer (NK) T cells and inducing interleukin (IL)-17 secretion in innate immune cells. The aim of the present study was to examine the effect of incomplete Freund's adjuvant (IFA) and L. monocytogenes treatment on the development of TID in NOD mice. This combined treatment of IFA and L. monocytogenes, a microbe that infects the liver and is primarily combatted by NK and cytotoxic T lymphocytes, was applied to mimic CFA treatment in pro-diabetic NOD mice. The combined IFA + L. monocytogenes treatment effectively delayed TID development in the NOD mice. In contrast to CFA, the IFA + L. monocytogenes treatment did not induce T cells or innate immune cells to secrete IL-17. However, increased levels of regulatory T cells were detected. Furthermore, IFA + L. monocytogenes mice exhibited higher levels of IgG2a, although no notable T helper 1 cell response was observed when compared with the CFA or IFA control treated mice. Therefore, combined IFA + L. monocytogenes treatment was shown to delay TID development in NOD mice via a novel mechanism, which was independent from the secretion of IL-17 by CFA-activated NKT cells. PMID- 26136918 TI - Detection of MMP-9 and TIMP-3 mRNA expression in the villi of patients undergoing early spontaneous abortion: A report of 30 cases. AB - The aim of the present study was to investigate the correlation of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase inhibitor (TIMP)-3 expression with spontaneous abortion (SA) during early pregnancy. The villus tissues of 30 SA cases and 20 requested abortion cases were collected during surgery and constituted the SA and normal abortion (NA) groups, respectively. The total villous RNA was extracted and the expression levels of MMP -9 and TIMP-3 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay to calculate the MMP-9/TIMP-3 mRNA ratio. The MMP-9 mRNA expression level and MMP-9/TIMP-3 mRNA ratio of the SA group were significantly higher than those of the NA group (P<0.01), while the TIMP-3 mRNA levels of the two groups were similar (P>0.05). The MMP-9 mRNA expression level of the SA group was higher than that of the NA group; thus, the MMP-9/TIMP-3 mRNA ratio was higher. These results suggest that the expression level of MMP-9 mRNA and the MMP 9/TIMP-3 mRNA ratio are associated with SA. PMID- 26136919 TI - Severe airflow obstruction in a patient with ulcerative colitis and toxic epidermal necrolysis: A case report. AB - Bronchiolitis is a rare condition mainly affecting the intralobular conducting and transitional small airways. The present study describes a case of severe airflow limitation in a patient with ulcerative colitis who developed toxic epidermal necrolysis following mesalazine therapy. Forced expiratory volume in one second was decreased and a flow-volume curve showed airflow limitation, but the single-breath diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO divided by alveolar volume (DLCO/VA) were not decreased. This rare clinical condition should be considered as a differential diagnosis for subjects presenting with sub-acutely developed airflow obstruction if the findings in chest computed tomography scans demonstrate hyperinflation but few low attenuation areas. Relatively well-preserved DLCO and DLCO/VA provide a clue to establishing the correct diagnosis. PMID- 26136921 TI - A novel method of combining Periodic Acid Schiff staining with Wright-Giemsa staining to identify the pathogens Penicillium marneffei, Histoplasma capsulatum, Mucor and Leishmania donovani in bone marrow smears. AB - Penicillium marneffei, Histoplasma capsulatum, Mucor and Leishmania donovani can lead to penicilliosis marneffei, histoplasmosis, mucormycosis and leishmaniasis, respectively, which, to a certain extent, share similar clinical manifestations. These pathogens are approximately the same size, therefore it is relatively difficult to rapidly diagnose the diseases. The aim of the present study was to explore a novel method that attempts to rapidly identify the pathogens of these diseases. In the Wright-Giemsa staining, the four pathogens were approximately the same size and mainly existed in macrophages. The multiplying P. marneffei had two nuclei, which were on both sides of the fungus, and had light cross-walls in the middle. H. capsulatum had a purplish nucleus, which occupied between one third and one-half of the spore. The cytoplasm was light blue. Peripheral spores were observed in the form of an empty, bright ring without color, like a capsule. Generally, Mucor were observed to have a long and lightly stained area, which could be easily confused with the Wright staining of dinuclear P. marneffei. L. donovani exhibited a deep-staining kinetoplast near the nucleus. In the Periodic Acid Schiff (PAS) staining, the pathogens of P. marneffei and H. capsulatum were distinct and stained red. Differentiation between P. marneffei and H. capsulatum relied on their modes of reproduction: P. marneffei depends on fission, when the pathogens stretch into sausage-shapes and are split by a cross-wall, while H. capsulatum depends on budding so that narrow-necked, single spores can be formed. With PAS staining, the cell walls and intracellular contents of Mucor and L. donovani were not stained, lightly stained or granulated and discontinuous. In conclusion, this method, combining PAS and Wright-Giemsa staining, is simple and rapid, and may contribute to the effective identification of the four pathogens. PMID- 26136920 TI - Recurrent pulmonary synovial sarcoma effectively treated with amrubicin: A case report. AB - Pulmonary synovial sarcoma is a rare but aggressive disease. The present study describes the case of a 68-year-old female with pulmonary synovial sarcoma. The patient was mistakenly treated for small cell lung cancer due to false-positive staining for synaptophysin and cluster of differentiation 56. Despite severe myelotoxicity, platinum-containing chemotherapies (cisplatin plus irinotecan and carboplatin plus etoposide) were not effective. As a third-line therapy, the patient received amrubicin (AMR) monotherapy. A partial response was achieved, and the patient was able to undertake ordinary daily life at home for 13 months from the initiation of AMR chemotherapy. Due to the atypical clinical condition and unusual response to chemotherapy in this patient, the pathological examination was repeated. The SS18 split-signal was detected in fluorescence in situ hybridization analysis. From these results, the tumor was diagnosed as a monophasic synovial sarcoma. To the best of our knowledge, this is the first case of a patient with pulmonary synovial sarcoma who underwent successful treatment with AMR. The present case could demonstrate a specific chemosensitivity of such a rare tumor. PMID- 26136922 TI - Effects of cyclic tension stress on the apoptosis of osteoclasts in vitro. AB - The aim of the present study was to investigate the effect of cyclic tension stress on osteoclast apoptosis in vitro using murine RAW264.7 cells treated with receptor activator of nuclear factor-kappaB. Using the EF3200 mechanical testing instrument with BioDynamic bioreactor system, cultured osteoclasts which were seeded in a silicone rubber membrane load carrier, were loaded with periodic cyclic stretch microstrain. The induced osteoclasts were subjected to 0, 5, 10 and 15% stretch microstrain for 1 h daily for three days. The number of tartrate resistant acid phosphatase-positive osteoclasts and the resorption area were assessed. Osteoclast apoptosis was detected by the Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide binding assay. The mRNA expression of Bcl 2, Bax, caspase-3 and cytochrome c was detected following force loading using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Compared with the cells under no cyclic tension stress, the number of osteoclasts and the resorption area were increased in the cells under 10 and 15% stretch microstrain. The Annexin V binding assay showed that the early apoptosis rate of the 5, 10 and 15% stretch microstrain groups was decreased compared with that of the control group. RT-qPCR results showed that the Bcl-2/Bax ratio was significantly increased in the cells subjected to 5, 10 and 15% stretch microstrain compared with that in the control cells (P<0.05), while the expression of cytochrome c in the 10 and 15% stretch microstrain groups was decreased significantly (P<0.05). No significant difference was observed between the cytochrome c expression of the 5% stretch microstrain group and that of the control group (P>0.05). The expression of caspase-3 in the 5, 10 and 15% stretch microstrain groups was decreased significantly compared with that in the control group (P<0.05). These data suggest that cyclic tension stress can inhibit apoptosis in osteoclasts, possibly by increasing the Bcl-2/Bax ratio, inhibiting the activity of caspase-3 and downregulating the expression of cytochrome c. PMID- 26136923 TI - Glioma localization and excision using direct electrical stimulation for language mapping during awake surgery. AB - The aim of this study was to investigate the method and significance of the application of direct electrical stimulation (DES) to the brain mapping of language functions during glioma surgery. A retrospective analysis of clinical data was performed for 91 cases of brain functional area glioma surgery under DES from January 2003 until January 2012. Following cortical electrical stimulation, 88 patients exhibited seizures involving facial or hand movements and 91 cases experienced language disorders such as counting interruption, naming errors or anomia. The most commonly observed areas of counting interruption were distributed on the posterior part of the left anterior central gyrus (47.7%), the operculum of the left inferior frontal gyrus (24.4%) and the triangular part of the left inferior frontal gyrus (12.8%). Postoperative magnetic resonance imaging demonstrated that overall excision was achieved in 53 cases and sub-overall excision was performed in 31 cases. A total of 42 cases (46.2%) exhibited no postoperative neurological dysfunction, 39 cases (42.9%) exhibited brief language dysfunction, 27 cases (29.7%) experienced brief limb movement disorder, and one case appeared to have permanent neurological dysfunction. DES was indicated to be a reliable and noninvasive method for the intraoperative positioning of language areas, and was able to resect gliomas in the language area with maximal safety. PMID- 26136924 TI - Long-term effects of ovariectomy on the properties of bone in goats. AB - Large animal models of osteoporosis are essential for osteoporosis research. However, the time required to establish an accurate osteoporosis model is unknown. Therefore, the aim of the present study was to establish a large animal model of osteoporosis in goats. In total, 14 Chinese goats were divided into an ovariectomized (OVX, n=7) or sham-operated (SHAM, n=7) group. Vertebral bodies were used to measure the bone mineral density (BMD) prior to the ovariectomy and at 24 months after the ovariectomy. In addition, the BMD of the femoral neck, femoral diaphysis and tibial diaphysis were measured 24 months postoperatively. Bone samples from the vertebral body, femoral head and femoral neck were scanned by micro-computed tomography (CT) to visualize the trabecular and cortical microstructure. Furthermore, the vertebral body, femoral head, femoral neck and tibial diaphysis were analyzed for mechanical strength. The BMD of vertebral body of the OVX group decreased significantly (P<0.01) at 24 months after the ovariectomy when compared with the baseline measurements. Micro-CT scans of the vertebral body revealed that the bone volume fraction, trabecular number, trabecular thickness and the degree of anisotropy decreased by 37.1, 36.7, 10.5 and 16.5%, respectively (P<0.01) in the OVX group when compared with the SHAM group. Additionally, the specific bone surface and trabecular spacing significantly increased by 37.7 and 62%, respectively in the OVX group (P<0.001). Cortical bone porosity in the vertebral body and femoral neck was greater in the OVX group when compared with the SHAM group (P<0.05). In addition, mechanical testing revealed a statistically significant difference between the vertebral bodies of the OVX group and the SHAM group. In conclusion, the present study demonstrated that an ovariectomy was able to induce significant osteoporosis and deterioration of mechanical properties in the bones of goats. PMID- 26136925 TI - Effect of osteopontin on the mRNA expression of ADAMTS4 and ADAMTS5 in chondrocytes from patients with knee osteoarthritis. AB - Previous studies have demonstrated that osteopontin (OPN) levels are elevated in the synovial fluid and articular cartilage, and are associated with the severity of knee osteoarthritis (OA). However, the role of OPN in the pathogenesis of OA has yet to be elucidated. The present study aimed to investigate the effects of OPN on the expression of the aggrecanases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5, in human OA chondrocytes, as they serve a key function in aggrecan degradation. Human OA chondrocytes were obtained from the knees of 16 patients with OA, and subsequently cultured in a monolayer. The chondrocytes were divided into three groups, which included the control (no treatment), N-OPN (treated with 100 ng/ml OPN, the normal circulating OPN concentration) and the H-OPN groups (treated with 1 ug/ml OPN, a high OPN concentration). Reverse transcription-quantitative polymerase chain reaction was performed to quantify the relative mRNA expression levels of ADAMTS4, ADAMTS5 and aggrecan in the chondrocytes. The mRNA expression levels of ADAMTS4 were significantly reduced in the N-OPN and H-OPN groups when compared with the control group (P<0.0001). In addition, the mRNA expression levels of ADAMTS4 were lower in the H-OPN group when compared with the N-OPN group (P<0.001). However, no statistically significant difference was observed in the relative mRNA expression levels of ADAMTS5 among the three groups (P>0.05). Furthermore, the mRNA expression levels of aggrecan were higher in the N-OPN and H-OPN groups when compared with the control group (P<0.0001), and a statistically significant difference was observed between the N-OPN and H-OPN groups with regard to the mRNA expression of aggrecan (P<0.0001). These results demonstrated that OPN may exert a protective effect in human OA chondrocytes against aggrecan degradation by suppressing the expression of ADAMTS4. PMID- 26136926 TI - B7 homolog 3 aggravates brain injury in a murine model of Streptococcus pneumoniae-induced meningitis. AB - Despite the application of antibiotics, Streptococcus pneumoniae (SP)-induced meningitis continues to be a life-threatening disease with a high fatality rate and an elevated risk of serious neurological sequelae, particularly in developing countries. In this study, the contribution of the co-stimulatory molecule B7 homolog 3 (B7-H3) to the pathogenesis of experimental SP-induced meningitis was investigated. Mice were challenged with the intracerebroventricular injection of serotype 3 SP with or without B7-H3. The clinical status of mice with SP-induced meningitis was examined by body weight loss and spontaneous motor activity with neurological scoring. Coronal brain sections were analyzed by counting Nissl positive neurons and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells. Protein expression of neuron-specific enolase (NSE) and S100B in brain tissues was examined with immunohistochemical staining. All experiments were performed in a randomized and blinded setting. By the intracerebroventricular injection of SP suspension, a murine model of pneumococcal meningitis was successfully established. In this SP-induced meningitis model, B7-H3 deteriorated the clinical status, as manifested by a decreased neurological score and increased body weight loss. Following the B7-H3 challenge, the number of Nissl-positive cells decreased and TUNEL-stained positive cells increased in the brain tissues of mice with SP meningitis, which demonstrates the enhancement of neuronal necrosis and apoptosis, respectively. Protein expression of NSE was decreased, while that of S100B was increased. These in vivo findings indicate that B7-H3 aggravates brain injury during the pathological process of experimental SP-induced meningitis. PMID- 26136928 TI - Adenosine monophosphate-activated protein kinase activation mediates the leptin induced attenuation of cognitive impairment in a streptozotocin-induced rat model. AB - Several lines of evidence have shown that the incidence of cognitive impairment in diabetic patients is significantly higher than that in healthy individuals, but the exact pathogenesis has not been fully elucidated. Furthermore, it has been suggested that leptin may have a therapeutic effect in cognitive dysfunction. The aim of the present study was to observe the effect of leptin on cognitive dysfunction in streptozotocin (STZ)-induced diabetic rats, and to explore whether adenosine monophosphate-activated protein kinase (AMPK) activation was involved in any potential therapeutic effect of leptin. Compared with control rats, STZ rats exhibited decreased levels of AMPK and a poor performance in the Morris water maze, while these changes were reversed by leptin. Furthermore, Compound C, an AMPK antagonist, significantly attenuated the leptin-induced cognitive function improvement in the STZ rats. In conclusion, these results suggest that AMPK activation may play a critical role in the leptin induced attenuation of STZ-induced cognitive impairment. PMID- 26136927 TI - Exploration of orbital and orbital soft-tissue volume changes with gender and body parameters using magnetic resonance imaging. AB - The aim of the present study was to examine the total orbital volume (TOV) and total orbital fat volume (TOFV) in normal orbits in different age groups and to investigate the correlation of these measurements with age, gender and body parameters by magnetic resonance imaging (MRI). MRI data were acquired retrospectively from a total of 1,453 subjects divided into five age groups with 10-year intervals. The TOV and TOFV were measured using T1-weighted MRI for each subject and body parameters were also obtained. The measurements demonstrated that TOV increased with age and that the volume was larger in men than in women. While weight and height exhibited positive correlations with TOV in male and female subjects in the 20-29, 30-39 and 40-49-year-old age groups, only weight showed a positive correlation with TOV in female subjects in the 50-59 and 60-69 year-old age groups. However, TOFV increased by age in all groups and the increments were larger in women than in men. These results provide basic information about the effect of age, gender and body parameters on TOV and TOFV. The variations in TOV are associated with orbital soft-tissues changes rather than with TOFV. PMID- 26136929 TI - Prognostic evaluation of preoperative serum C-reactive protein concentration in patients with epithelial ovarian cancer. AB - The aim of the present study was to evaluate correlations between preoperative C reactive protein (CRP) serum concentration and the clinical-pathological parameters of epithelial ovarian cancer (EOC), as well as cancer antigen 125 (CA125) concentration, in patients with EOC. The preoperative serum CRP concentrations of 107 patients with EOC were compared with values of 44 control patients and defined as positive if values were >8 mg/l. Correlations between CRP expression and serum CA125 concentrations, International Federation of Gynecologists and Obstetricians (FIGO) staging, lymph node metastasis, ascites and size of postoperative residual lesions were evaluated for the EOC cases. A total of 69% (74/107) of the EOC cases were CRP-positive, with a mean serum CRP concentration of 14.32 mg/l (versus 2.18 mg/l in the control patients) (P<0.001). A rank correlation analysis showed a positive correlation between serum CRP and CA125 concentrations (P<0.001). The five-year survival rate of the CRP-positive patients with EOC was significant lower than that of the patients that were CRP negative (33.3 vs. 75.8%, P<0.001). Non-parametric and multivariate analyses showed significant correlations between CRP concentrations and FIGO staging (P=0.001), lymph node metastasis (P=0.001) and ascites (P=0.033). In contrast to previous reports, the mean CRP serum concentration of the CRP-positive patients with EOC also correlated significantly with the CA125 values, and the increases in the CRP serum concentration in the Chinese patients were lower than those described for Caucasian EOC cases. In conclusion, the CRP serum concentration may be a useful clinical marker, solely or in combination with CA125, in patients with EOC. PMID- 26136930 TI - Effects of angiotensin II on transient receptor potential melastatin 7 channel function in cardiac fibroblasts. AB - The aim of the present study was to investigate the electrophysiological properties of transient receptor potential melastatin 7 (TRPM7) channels in the cell membranes of cardiac fibroblasts (CFs). CFs obtained from Sprague-Dawley rats were treated with six different concentrations of angiotensin (Ang) II for 12 h. The optimum concentration of Ang II for inducing fibrosis was selected by measuring collagen protein expression levels at each concentration. The optimum concentration of Ang II was then used to treat the CFs at five different time points, and the TRPM7 current across the CF membranes was recorded along with the collagen protein levels in each group. The optimum Ang II concentration for inducing fibrosis was found to be 1 nmol/l; when it was administered to CFs at 0, 6, 12, 24 and 48 h, the protein expression levels of TRPM7 and collagen III initially increased, reaching maximum levels at 12 h, and then decreased. This result positively correlated with the TRPM7 current levels on either side of the CF membranes: The TRPM7 current under the effect of the optimal Ang II concentration for inducing fibrosis was initially increased and then later decreased. This is one of the key mechanisms by which Ang II mediates the proliferation and apoptosis of CFs. This knowledge may be used to identify treatments for the prevention of cardiac fibrosis. PMID- 26136931 TI - Application of substrate utilization patterns and terminal restriction fragment length polymorphism analysis to characterize the oral bacterial community of healthy subjects and patients with periodontitis. AB - Understanding the association between the bacterial community and oral health status is essential for the diagnosis and therapy of periodontal diseases. The aim of the present study was to apply three methods [conventional culture, substrate utilization using the MicroRespTM system and terminal restriction fragment length polymorphism (T-RFLP)] to investigate the oral bacterial community in saliva from 20 healthy subjects and 20 patients with periodontitis. The three methods all revealed that there was a systematic change in the microbial ecological characteristics associated with oral health status. Compared with the control group, the oral bacterial flora in the patients with chronic periodontitis had a greater culturable population and altered preferred carbon source and TRFLP patterns. TRFLP analysis was found to give more information and exhibit a higher sensitivity than the substrate utilization and conventional culture methods. In conclusion, TRFLP analysis is a potentially rapid method to assess the composition of the oral microbial community and for the diagnosis of chronic periodontitis. PMID- 26136932 TI - Effect of Shenkang granules on the progression of chronic renal failure in 5/6 nephrectomized rats. AB - Shenkang granules (SKGs) are a Chinese herbal medicinal formula, consisting of rhubarb (Rheum palmatum L.), Salvia miltiorrhiza, milkvetch root [Astragalus membranaceus (Fisch.) Bunge] and safflower (Carthamus tinctorius L.). The aim of the present study was to investigate the effect of SKG on chronic renal failure (CRF) in 5/6 nephrectomized (5/6 Nx) rats. The rats were randomly divided into seven groups (n=10 per group) as follows: (i) 5/6 Nx (model group; 2.25 ml/kg/day normal saline); (ii) SKGL (low dose; 5/6 Nx treated with 2 g crude drug/kg/day SKG); (iii) SKGM (moderate dose; 5/6 Nx treated with 4 g crude drug/kg/day SKG); (iv) SKGH (high dose; 5/6 Nx treated with 8 g crude drug/kg/day SKG); (v) benazepril treatment group (5/6 Nx treated with 5 mg/kg/day benazepril); (vi) Shenkang injection (SKI) group (5/6 Nx with 13.3 ml/kg/day SKI); and (vii) sham operated group (2.25 ml/kg/day normal saline). After 30 days, the levels of microalbumin, total protein, serum creatinine, blood urea nitrogen and serum lipid were found to be significantly decreased in the SKGL and SKGM rats, showing histological improvement compared with the untreated 5/6 Nx rats, as determined by hematoxylin and eosin, and Masson's trichrome staining. In addition, SKG was found to significantly improve the levels of glutathione peroxidase and reduce the damage caused by free radicals to the kidney tissues. Furthermore, SKG prevented the accumulation of extracellular matrix by decreasing the expression of collagen I and III and inhibiting the expression of matrix metalloproteinases 2 and -9 in the renal tissue, as determined by western blot analysis. SKG was also shown to decrease the concentrations of serum transforming growth factor beta1, as determined by ELISA, and kidney angiotensin II, as determined using a radioimmunoassay kit. In conclusion, SKG was demonstrated to ameliorate renal injury in a 5/6 Nx rat model of CRF. Thus, SKG may exert a good therapeutic effect on CRF. PMID- 26136933 TI - Incremental value of resting three-dimensional speckle-tracking echocardiography in detecting coronary artery disease. AB - The aim of the present study was to investigate the incremental value of resting three-dimensional speckle-tracking echocardiography (3D-STE) in the detection of early-stage left ventricular dysfunction in patients with coronary artery disease (CAD). A total of 110 patients suspected of having CAD were recruited. All patients underwent 3D-STE and coronary artery angiography (CAG). They were divided to a CAD group and a normal group according to the results of CAG. Using 3D-STE software, the peak values of longitudinal strain (LS), circumferential strain (CS), radial strain (RS) and area strain (AS) and the time to peak value of these strains (T-LS, T-CS, T-RS and T-AS) were measured. A receiver operator characteristic curve (ROC) was used to analyze the sensitivity of these strains for the diagnosis of CAD. ROC analysis indicated that T-LS and composite indices combining the peak strain value and time to peak of LS, CS and AS have diagnostic value for the early detection of CAD; the area under the curve (AUC) values were 0.667, 0.692, 0.621 and 0.672 respectively (P<0.005). The composite index of longitudinal strain demonstrated the highest diagnostic value for CAD with 62% sensitivity and 76% specificity. These results indicate that 3D-STE has incremental value for the diagnosis of CAD in patients at rest. PMID- 26136934 TI - Pediatric patients with inflammatory bowel disease exhibit increased serum levels of proinflammatory cytokines and chemokines, but decreased circulating levels of macrophage inhibitory protein-1beta, interleukin-2 and interleukin-17. AB - Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition of the gastrointestinal tract. Although the causative events that lead to the onset of IBD are yet to be fully elucidated, deregulation of immune and inflammatory mechanisms are hypothesized to significantly contribute to this disorder. Since the onset of IBD is often during infancy, in the present study, the serum values of a large panel of cytokines and chemokines in pediatric patients (<18 years; n=26) were compared with age-matched controls (n=37). While elevations in the serum level of several proinflammatory and immune regulating cytokines were confirmed, such as interleukin (IL)-1beta, IL-5, IL-7, interferon (IFN)-gamma-inducible protein-10, IL-16, cutaneous T-cell-attracting chemokine, leukemia inhibitory factor, monokine induced by gamma-IFN, IFN-alpha2 and IFN gamma, notably decreased levels of IL-2, IL-17 and macrophage inhibitory protein 1beta were also observed. Therefore, while a number of proinflammatory cytokines exhibit increased levels in IBD patients, pediatric IBD patients may also exhibit certain aspects of a reduced immunological response. PMID- 26136935 TI - Frequency of SMN1 deletion carriers in a Mestizo population of central and northeastern Mexico: A pilot study. AB - Individuals who suffer from spinal muscular atrophy (SMA) exhibit progressive muscle weakness that frequently results in mortality in the most severe forms of the disease. In 98% of cases, there is a homozygous deletion of the survival of motor neuron 1 (SMN1) gene, and both parents carry the same heterozygous genetic abnormality in the majority of cases. Various population studies have been conducted to estimate the frequency of carriers and thereby identify the communities or countries in which children are at a high risk of being affected by SMA. However, the prevalence of SMA in Mexican populations has not yet been established. In the present pilot study, the frequency of the heterozygous deletion of the SMN1 gene was determined in two groups from northeastern (n=287) and central (n=133) Mexican Mestizo populations and compared with other ethnic populations. Amplification refractory mutation system polymerase chain reaction analysis yielded a disease carrier frequency of 11/420 (2.62%) healthy individuals, comprising 9/287 (3.14%) northeastern and 2/133 (1.5%) central Mexican individuals. In summary, no significant differences were identified between the northeastern and central populations of Mexico and other ethnic populations, with the exception of the general worldwide Hispanic population, which exhibited the lowest carrier frequency of 8/1,030. The results of the present study may be used to improve the evaluation procedure, and appear to justify further studies involving larger sample populations. PMID- 26136936 TI - Correlation between osteopontin and caveolin-1 in the pathogenesis and progression of osteoarthritis. AB - Previous studies have produced contradictory results with regard to the role of osteopontin (OPN) and caveolin-1 in the pathology of osteoarthritis (OA). Thus, the aim of the present study was to investigate the correlation between OPN and caveolin-1 in the pathogenesis and progression of OA. Cartilage tissue samples were obtained from 50 individuals, of which 40 had been diagnosed with OA and 10 were normal healthy individuals. The samples were ascribed to four groups, namely the normal, minor, moderate and severe groups, on the basis of the improved Mankin grading system. Immunohistochemistry was applied to analyse the expression of OPN and caveolin-1. OPN and caveolin-1 were detected in the tissues of all four groups. The mutual comparisons of OPN expression levels among the groups revealed statistically significant differences (P<0.05). In addition, the mutual comparisons of caveolin-1 expression levels among the four groups demonstrated statistically significant differences (P<0.05), with the exception of that between the moderate and severe groups (P>0.05). Improved Mankin grading system scores were shown to correlate with the average grey level of OPN expression in each group (r=-0.824, P<0.01) and the average grey level of caveolin-1 expression (r=0.725, P<0.01). Furthermore, a statistically significant negative correlation was observed between the average grey levels of OPN and caveolin-1 expression (r= 0.676, P<0.05). Therefore, the results of the present study indicated that the correlation between OPN and caveolin-1 may play a significant role in the pathogenesis and progression of OA. PMID- 26136937 TI - Effect of erythropoietin on the expression of dynamin-related protein-1 in rat renal interstitial fibrosis. AB - This study aimed to observe the expression of dynamin-related protein-1 (Drp-1) in the renal interstitium in a rat model of renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). In addition, the renoprotective effect of erythropoietin in this model was investigated. A total of 81 rats were randomly assigned to sham surgery, UUO model and treatment groups. Following surgery, the rats in the treatment group were subcutaneously administered erythropoietin at a dose of 3,000 IU/kg once a week until the time of sacrifice. Rats in the sham surgery and UUO model groups were administered an identical volume of normal saline. In each group, nine rats were chosen randomly for sacrifice on days 7, 14 and 21 after surgery for histological examination of renal tissue. Renal tissue specimens were examined by hematoxylin and eosin and Masson's trichrome staining. Immunohistochemical analysis was performed to determine the expression of Drp-1 in the renal interstitium. Renal function damage, as evaluated by the measurement of serum creatinine (Cr) and blood urea nitrogen (BUN) levels, was less severe in the treatment group compared with that in the model group at day 21 (P<0.01). Compared with the UUO model group, the renal interstitial injury score and fibrotic area of the treatment group were decreased markedly at the three time points (P<0.05). The expression level of Drp 1 in the treatment group was decreased markedly at the three time points compared with that in the model group (P<0.05). In conclusion, the expression of Drp-1 is increased in rat renal interstitial fibrosis, and erythropoietin may alleviate the degree of renal interstitial fibrosis by downregulating the expression of Drp 1. PMID- 26136938 TI - Quercetin promotes the osteogenic differentiation of rat mesenchymal stem cells via mitogen-activated protein kinase signaling. AB - The aim of the present study was to investigate the effects of quercetin on the mitogen-activated protein kinase (MAPK) signaling pathway in the osteogenic differentiation of rat mesenchymal stem cells (MSCs). A 3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide assay and an alkaline phosphatase (ALP) assay were used to determine the effects of quercetin (concentrations of 0.1, 1 and 10 umol/l) on the proliferation and differentiation of MSCs and the expression of ALP, respectively. In addition, through the introduction of inhibitors of p38 MAPK, extracellular signal-regulated kinase (ERK)1/2 and c-Jun NH2-terminal kinase (JNK), the effects of quercetin on the proteins, ALP, collagen type I (COL I) and bone gamma-carboxyglutamate protein (BGP), which are indicators of osteogenic differentiation, were investigated. Immunoblotting was performed to determine the phosphorylation levels of p38 MAPK, ERK1/2 and JNK, while fluorescent quantitative polymerase chain reaction was used to determine the mRNA expression levels of transforming growth factor (TGF)-beta1, bone morphogenetic protein (BMP)-2 and core binding factor (CBF)alpha1. At all the concentrations tested, the concentrations of 10, 1 and 0.1 umol/l quercetin were shown to promote the differentiation of MSCs and the expression of ALP, in which the concentration of 10 umol/l was optimal. When compared with the control group, the phosphorylation levels of p38 MAPK, ERK1/2 and JNK, the protein expression levels of ALP, COL I and BGP, and the mNRA expression levels of TGF-beta1, BMP-2 and Cbfalpha1 were increased in the quercetin-treated group. However, with the introduction of inhibitors, the levels of phosphorylated p38 MAPK, ERK1/2 and JNK, and the protein expression levels of ALP, COL I and BGP decreased. Furthermore, the mRNA expression levels of TGF-beta1, BMP-2 and CBFalpha1 decreased in the quercetin + SP600125 (inhibitor of JNK) and quercetin + PD98059 (inhibitor of ERK1/2) groups. Therefore, quercetin was demonstrated to promote the osteogenic differentiation of MSCs by activating the MAPK signaling pathway. The ERK1/2 and JNK signaling pathways regulate the expression of TGF-beta1, BMP-2 and CBFalpha1. Thus, activation of the ERK1/2 and JNK signaling pathways may play a leading role in the quercetin-promoted osteogenic proliferation and differentiation of MSCs. PMID- 26136939 TI - Protective effect of olmesartan against cardiac ischemia/reperfusion injury in spontaneously hypertensive rats. AB - Olmesartan, as a new angiotensin II receptor blocker, has shown beneficial effects on cardiovascular diseases. Nevertheless, the effect of olmesartan on ischemia/reperfusion (I/R) injury in the hypertensive heart has not been investigated. Therefore, the present study aimed to investigate the effect of olmesartan on I/R injury in spontaneously hypertensive rats (SHRs). Experimental groups were designed with a 2*2 factorial design for olmesartan and I/R effects. In the I/R group, the left anterior descending coronary artery (LAD) was ligated for 40 min followed by a 180-min reperfusion. In the sham group, SHRs underwent the same surgical procedure as the I/R group, with the exception that the suture passed under the LAD without being tightened. In the Olm-I/R group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the I/R group. In the Olm-sham group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the sham group. Infarct size was measured for the I/R and Olm-I/R groups. Blood pressure (BP), serum creatine kinase (CK), left ventricular mass index (LVMI), high mobility group box 1 (HMGB1) protein expression levels and hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA expression levels were measured for all four groups. Olmesartan significantly reduced BP and LVMI in the olmesartan-treated SHRs compared with those in the SHRs that were not treated with olmesartan. HMGB1 and HIF-1alpha expression levels were significantly decreased in the Olm-sham and Olm-I/R groups compared with those in the sham and I/R groups, respectively. The proportional increase in HIF-1alpha expression due to I/R was greater in the olmesartan-treated rats than in the untreated rats. Serum CK levels were significantly reduced in the Olm-I/R group compared with those in the I/R group. In conclusion, olmesartan ameliorates left ventricular hypotrophy and protects the heart against I/R injury in addition to lowing BP in SHRs. The protective effect of olmesartan may be partly due to its antioxidative and anti-inflammatory properties. PMID- 26136940 TI - Effect of lysosomal and ubiquitin-proteasome system dysfunction on the abnormal aggregation of alpha-synuclein in PC12 cells. AB - The aim of this study was to investigate the effect of lysosomal and ubiquitin proteasome system dysfunction on the abnormal aggregation of alpha-synuclein, and to analyze its role in the pathogenesis of Parkinson's disease (PD). PC12 cells subjected to nerve growth factor-induced differentiation were used as the cell model to study the dopaminergic neurons, and the lysosomal and proteasomal inhibitors trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane (E64) and, respectively, were used exclusively and in combination to treat the PC12 cells. The viability and metabolic state of the cells was assessed using the MTT assay; flow cytometry was used to measure the rate of cell apoptosis; and the double immunofluorescence method was applied to observe the formation of thioflavin S- and alpha-synuclein protein-positive aggregates and inclusion bodies in the PC12 cells. In addition, the Hoechst 33258 staining method was used to observe the apoptosis of the alpha-synuclein protein and thioflavin-S double-labeled cells. Following the administration of the lysosomal and proteasomal pathway inhibitors, the cell viability decreased in a concentration-dependent manner and the cell apoptosis rate increased. The proportion of PC12 cells with alpha-synuclein protein-positive aggregates and inclusion bodies in the E64 group was 7.94%, compared with 20.33 and 36.77% in the lactacystin and combination treatment groups, respectively. Statistical analysis indicated that the number of inclusion body-positive cells in the treatment groups was significantly higher than that in the control group (3.78%) (P<0.05). Apoptosis was evident in the double-positive cells with alpha-synuclein protein-positive inclusion bodies (17.29+/-1.54%). In conclusion, lysosomal and proteasomal dysfunction may play an important role in the pathogenesis of PD through the induction of abnormal alpha-synuclein protein aggregation in dopaminergic neurons. PMID- 26136941 TI - Impact of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of stage IA adenocarcinoma of the lung: Correlation between computed tomography images and EGFR and KRAS gene mutations. AB - The aim of the present study was to compare pathological diagnoses, as determined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, with conventional radiological features. In addition, the present study aimed to evaluate the correlation among clinical characteristics, computed tomography (CT) images and gene mutation status in patients with stage IA adenocarcinoma of the lung. A total of 212 patients with stage IA lung adenocarcinoma were included in the study. The patients were classified into pure ground-glass opacity (pGGO), mixed GGO (mGGO) and solid GGO (sGGO) by CT imaging. Histological subtype was classified according to the IASLC/ATS/ERS classification of lung adenocarcinoma. In addition, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) mutation assays were performed, and 36.8% of patients (78/212) were determined to have an EGFR mutation, while 8.5% of patients (18/212) were found to have a KRAS mutation. According to the IASLC/ATS/ERS classification, 44 cases were diagnosed as adenocarcinoma in situ (AIS; 20.8%), 62 cases were diagnosed as minimally invasive adenocarcinoma (MIA; 29.2%) and 106 cases were classified as invasive adenocarcinoma (IAC; 50.0%). pGGO image patterns were observed in 39.2% of patients (n=83), while mGGO and sGGO patterns were observed in 28.8% (n=61) and 32.0% (n=68) of patients, respectively. From pGGO to sGGO, cases of AIS and MIA were shown to have a decreasing trend, while IAC cases exhibited an increasing trend (P=0.036). Analysis of the correlation between CT image patterns and gene mutations demonstrated that L858R point mutations, exon 19 deletions and KRAS mutations were more common in lesions with a lower GGO proportion (P=0.029, 0.027 and 0.018, respectively). Therefore, according to the IASLC/ATS/ERS classification, GGO imaging patterns were shown to correlate with subtypes of adenocarcinomas. In addition, EGFR and KRAS mutations were found to be associated with lesions with a low GGO proportion. Therefore, analysis of GGO lesions may offer useful indications of the histological subtype of an adenocarcinoma in patients with stage IA lung adenocarcinoma, and predictive value for EGFR and KRAS mutations. PMID- 26136942 TI - Extensive bone metastases as the initial symptom of papillary thyroid microcarcinoma: A case report. AB - A 53-year-old female patient presented with lumbar and pelvic pain. The 18F fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography scintigraphy showed extensive bone destruction with hypermetabolic osteolysis, with increased 18F-FDG uptake. The histological examination of the pubic bone lesion revealed a metastatic tumor. Neither chemotherapy nor radiotherapy could control the condition. More than a year later, the patient underwent a total thyroidectomy with cervical lymph node clearance. The histological examination revealed a papillary thyroid microcarcinoma (PTMC) in the left lobe with capsular invasion. 131I treatment with thyroid hormone withdrawal followed. The 131I whole body scintigraphy showed extensive uptake in the basic thyroid deposits, most bones and both lungs. Three months after the 131I treatment, the patient succumbed to cachexia. The present case indicated that not all PTMCs have excellent prognosis and that, despite being rare, clinically significant metastases can arise from a PTMC. PMID- 26136943 TI - High levels of serum lactate dehydrogenase correlate with the severity and mortality of idiopathic pulmonary arterial hypertension. AB - Liver dysfunction reflects the status of heart failure, and previous studies have demonstrated that serum lactate dehydrogenase (S-LDH) levels are increased in patients exhibiting heart failure and liver dysfunction. Right heart failure is a main characteristic of idiopathic pulmonary arterial hypertension (IPAH). The aim of the present study was to assess the prognostic significance of S-LDH levels in patients with IPAH. S-LDH levels were determined in 173 patients with IPAH, and these patients were subclassified into two groups according to a defined upper reference limit of S-LDH (250 IU/l). Right heart catheterization was performed in all patients. A total of 53 patients were found to have elevated S-LDH to >=250 IU/l. In a mean follow-up period of 31.2+/-17.9 months, 57 patients succumbed. In the group with lower S-LDH levels (S-LDH <250 IU/l), 16.7% of the patients succumbed, compared with 69.8% of patients in the group with higher S-LDH levels (S-LDH >=250 IU/l). The Kaplan-Meier survival curves demonstrated that patients with higher S-LDH levels had a significantly lower survival rate than did those with lower S-LDH levels (log-rank test, P<0.001). Cox proportional hazard analyses identified reduced body mass index, reduced cardiac index, elevated World Health Organization functional class, higher S-LDH and an absence of PAH targeted therapy as significant predictors of adverse outcomes. In conclusion, elevated S-LDH is a risk factor for mortality in patients with IPAH. PMID- 26136944 TI - Hydrogen gas inhalation protects against liver ischemia/reperfusion injury by activating the NF-kappaB signaling pathway. AB - Hydrogen has been demonstrated to function as a novel antioxidant and exert therapeutic antioxidant activity in a number of diseases. The present study was designed to investigate the effect of hydrogen inhalation on liver ischemia/reperfusion (I/R) injury in rats. The portal triad to the left lobe and the left middle lobe of the liver were completely occluded for 90 min. This was followed by reperfusion for 180 min. The rats subsequently underwent syngeneic orthotopic liver transplantation. Inhalation of various concentrations (1, 2 and 3%) of hydrogen gas and its administration for different durations (1, 3 and 6 h) immediately prior to the I/R injury allowed the optimal dose and duration of administration to be determined. Liver injury was evaluated through biochemical and histopathological examinations. The expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, were measured by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction (qPCR). Liver nuclear factor kappaB (NF-kappaB) was detected by qPCR and western blot analysis. Inhalation of hydrogen gas at 2% concentration for 1 h significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the expression of cytokines, including IL-6, TNF-alpha, early growth response protein 1 (Egr-1) and IL-1beta, and morphological damage. In addition, the mRNA and protein expression levels of NF-kappaB, heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2) and zinc finger protein A20 (A20) in rats where only the donors received hydrogen were significantly increased compared with those in rats where both the donor and recipient, or only the recipient received hydrogen. The results indicate that hydrogen inhalation at 2% concentration for 1 h prior to liver transplantation protected the rats from ischemia/reperfusion injury by activation of the NF kappaB signaling pathway. PMID- 26136945 TI - Antioxidant and anti-excitotoxicity effect of Gualou Guizhi decoction on cerebral ischemia/reperfusion injury in rats. AB - Stroke is the leading cause of disability in adults and the second most common cause of mortality worldwide. There is currently intense interest in the use of natural products in the treatment of the condition. The aim of this study was to investigate the effect of Gualou Guizhi decoction (GLGZD) on rats subjected to cerebral ischemia/reperfusion injury and the possible mechanisms involved. Cerebral ischemia/reperfusion injury was induced by the middle cerebral artery occlusion method. Ischemic injury was assessed by estimating neurological function and measuring brain infarct volume, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method was employed to examine ischemia-induced apoptosis. The levels of the antioxidative enzyme superoxide dismutase (SOD) and the concentrations of the non-enzymatic scavenger glutathione (GSH) and malondialdehyde (MDA) were measured to investigate the antioxidant mechanisms. In addition, the levels of excitatory amino acids (EAAs) and glutamate receptor 1 (GluR1) were examined using an automatic amino acid analyzer and immunohistochemical analysis. The administration of GLGZD attenuated the cerebral ischemia/reperfusion injury-induced neural deficits and cerebral infarct volume, reduced the levels of MDA and EAAs (glutamate and aspartate), significantly increased the activity of the antioxidant GSH and notably elevated the activity of SOD. Consistently, GLGZD inhibited ischemia-induced apoptosis and downregulated the expression of GluR1. In conclusion, this study suggested that GLGZD exerts a neuroprotective effect on focal cerebral ischemia/reperfusion injury through the modulation of multiple antioxidant and anti-excitotoxicity pathways. PMID- 26136946 TI - Study of correlation between polymorphism of ST6GALNAC2 and susceptibility to IgA nephropathy. AB - The aim of the present study was to explore the correlation between single nucleotide polymorphisms (SNPs) rs3840858 and rs2304921 in a specific alpha-2,6 sialyltransferase gene, ST6GALNAC2, and the susceptibility to immunoglobulin (IgA) nephropathy (IgAN). The distributions of genotypes of SNPs rs3840858 and rs2304921 in ST6GALNAC2 were detected by direct sequencing. The distributions of the genotype and allele frequencies of rs3840858 in patients with IgAN were significantly different from those in the control group (genotypes, P=0.001; alleles, P=0.001). The DI genotype ratio (17.8%) in the IgAN group was higher than that in the control group (5.6%) and the I allele frequency (8.9%) in the IgAN group was higher than that in the control group (2.8%). Univariate logistic regression analysis indicated that rs3840858 polymorphism is a risk factor of IgAN (P=0.001). The risk of developing IgAN in individuals who carried the DI genotype was 3-fold higher than that in individuals who carried the DD genotype [odds ratio (OR)=3.676, 95% confidence interval (CI)=1.284-10.519], and the risk of developing IgAN in individuals who carried the I allele was higher than that in individuals who carried the D allele (OR=3.415, 95% CI=1.223-9.531). The distributions of the genotype (AA, AG and GG) and allele (A and G) frequencies of rs2304921 did not have a statistically significant difference between patients with IgAN and those without (P>0.05). The SNP rs3840858 in the ST6GALNAC2 gene may be associated with the risk of developing IgAN in the population studied; however, polymorphism of rs2304921 appears to be irrelevant to the risk of developing IgAN in this population. PMID- 26136947 TI - Hepatoid adenocarcinoma of the stomach: A case report and literature review. AB - Hepatoid adenocarcinoma (HAC) is a rare form of gastric cancer that has unique clinicopathological features and an extremely poor prognosis. The present case report describes a patient who was referred to the No. 461 Hospital of PLA (Changchun, China) due to nausea and occasional vomiting of acid/water. The patient was diagnosed with gastric signet-ring cell carcinoma and surgery was recommended. A total gastrectomy was performed on the operable lesion. Histopathological analysis revealed that the tumors exhibited two pathological changes: HAC and signet-ring cell carcinoma differentiation. Furthermore, the tumor cells were immunohistochemically positive for alpha-fetoprotein, cytokeratin low/high molecular weight, Cam5.2, cytokeratin 7, p53, epithelial membrane antigen and carcinoembryonic antigen. Previous studies and our experience have suggested that HAC is an aggressive type of adenocarcinoma; however, radical surgery and chemotherapy may positively impact clinical outcomes. PMID- 26136948 TI - Langerhans cell histiocytosis with multisystem involvement in an infant: A case report. AB - Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocyte-like cells, with a wide range of clinical presentations that vary from a solitary lesion to more severe multifocal or disseminated lesions. The disease can affect any age group; however, the peak incidence rate is in infants aged between 1 and 3 years-old. Diagnosis of LCH should be based on the synthetical analysis of clinical presentations, in addition to features of imaging and histopathology. Although certain cases regress spontaneously, other patients require systemic chemotherapy together with the administration of steroids. The present study reports the case of an infant with LDH with multisystem involvement, including that of the bone, skin, orbit, spleen and lungs. The patient received chemotherapy and obtained rapid improvement in the involved systems. A total of 2.5 years after completion of the therapy, the patient still remains in follow-up and no evidence of active disease has been noted. PMID- 26136949 TI - Akt/hypoxia-inducible factor-1alpha signaling deficiency compromises skin wound healing in a type 1 diabetes mouse model. AB - The aim of the present study was to investigate the mechanisms for impaired skin wound healing in subjects with diabetes. Type 1 diabetes (T1DM) was induced in BALB/c mice using streptozotocin. One month after the establishment of the T1DM mouse model, a wound was formed on the back of the mice, and tissues from the wounds and the margins were collected on days 0, 3, 7 and 10. Protein levels of cluster of differentiation 31 (CD31) were detected using immunohistochemistry, and the mRNA levels of Akt, hypoxia-inducible factor-1alpha (Hif-1alpha), vascular endothelial growth factor (Vegf), VEGF receptor 2 (Vegfr2), stromal cell derived growth factor-1alpha (Sdf-1alpha) and CXC chemokine receptor 4 (Cxcr4) were determined using reverse transcription-quantitative polymerase chain reaction analysis. The corresponding protein levels were determined using western blotting. The skin wound healing rate in the T1DM mice was significantly lower than that in the control mice, and the protein level of CD31 in the wounded skin of the T1DM mice was significantly decreased. Furthermore, the overall mRNA levels of Akt, Hif-1alpha, Vegf, Vegfr2, Sdf-1alpha and Cxcr4 in the T1DM mice were significantly lower than those in the control mice, and similar trends were observed in the protein levels. In conclusion, skin wound healing was impaired in the T1DM mice, and this may have been caused by a deficiency of Akt/HIF-1alpha and downstream signaling, as well as delayed angiogenesis. PMID- 26136950 TI - Expression and prognostic value of estrogen receptor beta in patients with triple negative and triple-positive breast cancer. AB - The aim of the present study was to investigate the expression of estrogen receptor beta (ERbeta) in triple-negative and triple-positive breast cancer patients, and evaluate its utility as a prognostic factor. Between January 2000 and December 2010, primary tumor tissue samples were collected from 234 subjects, including 107 triple-negative and 127 triple-positive breast cancer patients. The samples were embedded in paraffin and immunohistochemical staining was conducted to determine the expression levels of ERbeta. The Kaplan-Meier method was used to analyze patient survival rates. ERbeta expression was observed in 38/107 patients (35.5%) with triple-negative breast cancer and 63/127 patients (49.6%) with triple-positive breast cancer. The ERbeta expression rate was significantly decreased in the patients with triple-negative breast cancer, as compared with those with triple-positive breast cancer (P=0.03). Analysis of the survival rates indicated that patients with triple-negative breast cancer and positive ERbeta expression exhibited poor disease progression-free survival (DFS) compared with those with negative ERbeta expression (P=0.021). However, no statistically significant difference was observed in the DFS between the triple-positive breast cancer patients with positive and negative ERbeta expression. Therefore, the expression of ERbeta varies between triple-negative and triple-positive breast cancer patients. In addition, positive expression of ERbeta indicates a poor prognosis in triple-negative breast cancer patients; however, this is not the case for triple-positive breast cancer patients. PMID- 26136951 TI - Association between EML4-ALK fusion gene and thymidylate synthase mRNA expression in non-small cell lung cancer tissues. AB - This study aimed to investigate the association of the mRNA expression of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene with that of thymidylate synthase (TYMS) in non-small cell lung cancer (NSCLC) tissues. Quantitative polymerase chain reaction was used to detect the expression of EML4-ALK fusion gene and TYMS mRNA in 257 cases of NSCLC. The positive rate of EML4-ALK fusion gene was 4.28% in the NSCLC tissues (11/257), and was higher in nonsmokers than in smokers (P<0.05); TYMS mRNA expression was detected in 63.42% (163/257) of cases. An association of the EML4 ALK fusion gene with TYMS expression was detected; a low expression level of TYMS mRNA was observed more frequently when the EML4-ALK fusion gene was present than when it was not detected (P<0.05). In conclusion, patients positive for the EML4 ALK fusion gene in NSCLC tissues are likely to have a low expression level of TYMS, and may benefit from the first-line chemotherapy drug pemetrexed. PMID- 26136952 TI - Changes in FABP1 and gastrin receptor expression in the testes of rats that have undergone electrical injury. AB - Testicular trauma may occur due to accidental electrical injury. The aim of this study was to investigate alterations in the levels of fatty acid-binding protein 1 (FABP1) and gastrin receptor (gastrin R) in the testes following electrical injury. Sprague-Dawley rats were divided into control, fatal electrocution (220 V, 50 Hz, 60 sec) and electrical injury (220 V, 50 Hz, 60 sec) groups (n=8 per group). The animals in the fatal electrocution and electrical injury groups were deeply anesthetized with sodium pentobarbital prior to each treatment, in which the current was delivered via an anode connected to the left foreleg and a cathode to the right hindleg. The rats that survived were subsequently sacrificed by cervical dislocation. Control animals received cervical dislocation alone. Immunohistochemical analysis was performed to evaluate the protein expression of FABP1 and gastrin R in the testes. Sections were evaluated by digital image analysis. The expression levels of FABP1 and gastrin R were significantly increased following electrical injury, supported by an increase in the integrated optical density (IOD) when compared with that in the control group (P<0.05). However, no significant difference was found in FABP1 and gastrin R expression levels between the fatal electrocution and control groups. In summary, the protein expression levels of FABP1 and gastrin R were found to be significantly altered by electrical injury, suggesting that these two proteins may be important in underlying mechanisms of testicular injury during electrical injury. The findings indicate that such alterations would be reflected in abnormal testicular function. PMID- 26136953 TI - Sporadic lymphangioleiomyomatosis with bloody sputum as an initial symptom: A case report and review of the literature. AB - Lymphangioleiomyomatosis (LAM) is an extremely rare lung disease affecting females of a childbearing age. The condition occurs sporadically or in association with tuberous sclerosis complex. The diagnosis of LAM is often delayed since the clinical symptoms and signs are non-specific. The present study reports the a case of a patient with LAM, in which bloody sputum was presented as the initial symptom. The 43-year-old female had experienced a small amount of bloody sputum over the previous five years. The patient was admitted to the Department of Respiratory Medicine at Taizhou People's Hospital (Taizhou, China) in 2012, reporting symptoms of a cough, shortness of breath and bloody sputum over the previous 10 days. A high-resolution computed tomography scan revealed multiple small circular thin-walled translucent areas in both lung fields. The initial diagnosis of the patient was LAM. A biopsy was performed using a video assisted thoracoscopy. In conclusion, increased awareness and early diagnosis and treatment were determined to be key factors in ensuring a satisfactory prognosis. PMID- 26136955 TI - Effects of DLX2 overexpression on the osteogenic differentiation of MC3T3-E1 cells. AB - Distal-less genes (DLX) play important roles in regulating organism development. DLX2 is crucial for the differentiation and development of the primordium, which determines the subsequent development and phenotype of the maxillofacial skeletal patterns, and is the primary candidate gene that regulates the development of the first branchial arch. The aim of the present study was to investigate the effects of DLX2 overexpression on the osteogenic differentiation of MC3T3-E1 cells in vitro. A DLX2-expression retrovirus vector was constructed by subcloning with a murine stem cell virus (MSCV) and verified by sequencing. MC3T3-E1 cells were transfected with pMSCV-DLX2 and stable clones were selected with puromycin. The mRNA and protein expression levels of DLX2 were determined using quantitative polymerase chain reaction (PCR) and western blot analysis, respectively. In addition, the expression levels of the osteogenic biomarkers, alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor (RUNX)2 and Msh homeobox (MSX)2, were assessed by quantitative PCR. ALP detection and Alizarin red staining were conducted to evaluate the effect of DLX2 overexpression on osteogenic differentiation. The data were analyzed by analysis of variance using the Student-Newman-Keuls method. Successful pMSCV-DLX2 construction, as verified by direct sequencing, enabled DLX2 overexpression in vitro. Enhanced ALP activity and Alizarin red staining were observed in the MC3T3 E1-DLX2 cells when compared with the control group. During osteogenic induction, DLX2 overexpression was demonstrated to upregulate ALP and MSX2 expression at the early stage and OCN expression at the late stage, while no statistically significant difference was observed in RUNX2 expression when compared with the control group. Therefore, DLX2 overexpression in vitro induced the osteogenic differentiation of MC3T3-E1 cells via upregulating bone formation-associated genes, such as ALP and MSX2. PMID- 26136954 TI - Differentiation between Graves' disease and painless thyroiditis by diffusion weighted imaging, thyroid iodine uptake, thyroid scintigraphy and serum parameters. AB - The aim of the present study was to assess the apparent diffusion coefficient (ADC) in diffusion-weighted imaging (DWI), thyroid radioactive iodine uptake (RAIU), thyroid scintigraphy and thyrotropin receptor antibody (TRAb) levels in the differential diagnosis between Graves' disease (GD) and painless thyroiditis (PT). A total of 102 patients with GD and 37 patients with PT were enrolled in the study. DWI was obtained with a 3.0-T magnetic resonance scanner, and ADC values were calculated. RAIU and thyroid scintigraphy were performed. Tissue samples were obtained from patients with GD (6 cases) following thyroidectomy, and from patients with PT (2 cases) following biopsy. Receiver operating characteristic (ROC) curves were drawn, optimal cut-off values were selected, and the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were assessed. It was found that the ADC, TRAb and RAIU were significantly higher in GD than in PT (P<0.05). ROC curves showed areas under the curves for RAIU, ADC and TRAb that were >0.900. RAIU was the reference method. Sensitivity, specificity, accuracy, PPV and NPV were 96.078, 91.892, 95.000, 97.059 and 89.474% for ADC, and 88.235, 75.676, 84.892, 90.909 and 70.000% for TRAb, after the optimal thresholds of 1.837*10-3 mm2/sec and 1.350 IU/ml were determined respectively. Histopathology showed that tissue cellularity in PT was much higher than in GD due to massive lymphocytic infiltration. The results of the present study indicate that RAIU, ADC and TRAb are of diagnostic value for differentiating between GD and PT. DWI has great potential for thyroid pathophysiological imaging because it reflects differences in tissue cellularity between GD and PT. PMID- 26136956 TI - Avastin(r) in combination with gemcitabine and cisplatin significantly inhibits tumor angiogenesis and increases the survival rate of human A549 tumor-bearing mice. AB - The aim of this study was to investigate the effect of Avastin(r) in combination with gemcitabine and cisplatin (GP) on the tumor growth of A549 tumor-bearing mice and the potential anti-tumor mechanism. A total of 30 human A549 tumor bearing nude mice were randomly divided into the Avastin, chemotherapy and combined treatment groups for treatment with an intraperitoneal injection of Avastin (5 mg/kg) (Avastin group); an intraperitoneal injection of gemcitabine (4 mg/kg) and cisplatin (4 mg/kg) (chemotherapy group); or intraperitoneal injections of Avastin and GP (combined treatment group). The mice were observed for 30 days and the tumor growth, survival and body weight of the mice in the three groups were analyzed. The protein level of vascular endothelial growth factor (VEGF) in the tumor tissues was analyzed by ELISA. The vascular density and structural changes of the tumor were analyzed using immunohistochemistry. Compared with the Avastin and chemotherapy groups, the tumor growth of mice in the combined treatment group was significantly inhibited, and the survival rate of the mice was increased significantly. No difference in body weight was observed among the three groups of mice (P>0.05). The levels of VEGF in the combined treatment group tumor tissues were significantly reduced compared with those in the chemotherapy group tumor tissues (P<0.05). Furthermore, the vessel density of the tumor tissue in the combined treatment group was significantly reduced compared with that in the chemotherapy group (P<0.05), and the number of normal vessels in the combined treatment group tumors was significantly higher than that in the chemotherapy group tumors after 7 days of treatment (P<0.05). In conclusion, Avastin can significantly decrease the level of VEGF in tumor tissue, inhibit tumor angiogenesis and promote the normalization of tumor vascular structure, which may explain the enhanced efficacy of Avastin in combination with chemotherapy. PMID- 26136957 TI - Downregulation of microRNA-21 enhances radiosensitivity in nasopharyngeal carcinoma. AB - Radioresistance severely restricts the clinical treatment of nasopharyngeal carcinoma (NPC). microRNAs (miRs) have been demonstrated to affect cancer progression and radiosensitivity. Thus, the aim of the present study was to identify miRs associated with radioresistance in NPC. A radioresistant NPC cell line (CNE-2-1) was established by continuously exposing CNE-2 cells to radiation. Subsequently, high-throughput sequencing technology was used to detect the regulation of miRs in radioresistant CNE-2-1 cells, and it was observed that miR 21 was among the three most upregulated miRs in CNE-2-1 cells. Therefore, the expression levels of miR-21 were quantified using reverse transcription quantitative polymerase chain reaction. Finally, the function of miR-21 was investigated by downregulating the expression in the CNE-2-1 cells. The results indicated that the expression of miR-21 was significantly increased in the CNE-2 1 cells, as compared with the CNE-2 cells. In addition, downregulation of miR-21 resulted in enhanced radiosensitivity in the CNE-2-1 cells, as demonstrated by the inhibition in cell viability of these radioresistant cells. Further analysis indicated that miR-21 was able to inhibit the proliferation of CNE-2-1 cells at the G1 phase of the cell cycle. Therefore, these results indicated that miR-21 was able to regulate radioresistance in NPC cells; however, further studies are required to confirm this hypothesis. PMID- 26136958 TI - Expression and activity levels of chymase in mast cells of burn wound tissues increase during the healing process in a hamster model. AB - The present study aimed to investigate the changes in the expression levels and activity of mast cell chymase in the process of burn wound healing in a hamster model of deep second-degree burn. The hamster model was established by exposing a ~3 cm diameter area of bare skin to hot water (75 degrees C) for 0, 6, 8, 10 or 12 sec. Tissue specimens were collected 24 h after burning and histological analysis revealed that hot water contact for 12 sec was required to produce a deep second-degree burn. Quantitative polymerase chain reaction and a radioimmunoassay were used to the determine changes in chymase mRNA expression levels and activity. The mRNA expression levels and activity of chymase were increased in the burn wound tissues when compared with the normal skin. However, no statistically significant differences were observed in mast cell chymase activity amongst the various post-burn stages. Chymase mRNA expression levels peaked at day 1 post-burn, subsequently decreasing at days 3 and 7 post-burn and finally increasing again at day 14 post-burn. In summary, a hamster model of deep second-degree burn can be created by bringing the skin into contact with water at 75 degrees C for 12 sec. Furthermore, the mRNA expression levels and activity of chymase in the burn wound tissues increased when compared with those in normal skin tissues. PMID- 26136959 TI - Expression of signal transducer and activator of transcription 3 and its phosphorylated form is significantly upregulated in patients with papillary thyroid cancer. AB - The aim of the present study was to investigate the expression of signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (pSTAT3) in tissues of papillary thyroid cancer (PTC) in comparison with the expression in adjacent normal tissues. The expression of STAT3, pSTAT3, fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor-C (VEGF C) was examined in tissues of 42 cases of PTC and the adjacent normal tissues of 20 of the 42 PTC cases using immunohistochemistry and western blotting. The association between the expression levels and the clinicopathological features was analyzed. The expression of STAT3, pSTAT3, FGF2 and VEGF-C in the PTC tissues (76.2, 42.9, 81.0 and 73.8%, respectively) was significantly higher than that in the normal tissues (P<0.05). In the PTC tissues, the expression of STAT3 was linearly correlated with the levels of pSTAT3 and VEGF-C (P<0.05). In conclusion, STAT3 and pSTAT3 are significantly upregulated in PTC tissues, and may potentially be used as markers to screen for PTC with lymph node metastasis. PMID- 26136960 TI - Rapid growth and osteogenic differentiation of mesenchymal stem cells isolated from human bone marrow. AB - Mesenchymal stem cells (MSCs) are involved in bone formation in the embryo, bone repair and remodeling. The differentiation of these cells is a complex multistep pathway that involves discrete cellular transitions and is similar to that which occurs during hematopoiesis. MSCs have self-renewal capacity without differentiation in long-term culture. In the present study, MSCs were isolated from human bone marrow and characterized by the presence of cluster of differentiation 105 marker using the labeled streptavidin biotin method. The MSCs were cultured in Dulbecco's modified Eagle's medium supplemented with fetal bovine serum, ascorbic acid, beta-glycerol phosphate and dexamethasone to differentiate into osteoblasts. Biological in vitro analysis showed the rapid proliferation of the MSCs. Further evaluation of specific osteogenic markers using von Kossa staining and the alkaline phosphate assay demonstrated that the MSCs were stimulated to differentiate into osteoblast-lineage cells. This mesengenic potential indicated that the bone marrow-derived cells were multipotent MSCs. The findings of this study show that bone marrow can be a legitimate source of MSCs for the production of osteoblasts for utilization in bone replacement therapy. PMID- 26136961 TI - Application status of tamoxifen in endocrine therapy for early breast cancer. AB - The aim of the present study was to investigate the application status of tamoxifen as an adjuvant treatment for early-stage breast cancer. Data for patients with early breast cancer were collected from an information management system for breast cancer in a single hospital between 1989 and 2012. The inclusion criteria included no distant metastasis during diagnosis with breast cancer, and a diagnosis of estrogen and/or progesterone receptor-positive breast cancer, or an unclear hormonal receptor status with tamoxifen used as the preferred drug. A total of 2,738 patients were selected, with 99.4% female and 0.6% male patients. Within females, 75.7% were premenopausal when diagnosed with early breast cancer, 24.3% were postmenopausal, and the median age of menopause was 47 years. The percentage of tamoxifen preference in adjuvant therapy was 97.3% prior to 2000, which decreased to 60.4% in 2011. Tamoxifen preference among premenopausal patients reduced from 97.3% prior to 2000 to 89.5% in 2011, while in postmenopausal patients tamoxifen preference declined from 97.4% prior to 2000 to 22.7% in 2011. One-year duration of tamoxifen treatment accounted for 79.4% of cases, while five-year duration accounted for 24.7%. The rate of one-year disease free survival (DFS) was 98.5% and of five-year DFS was 89.1%. Patients with early breast cancer had a one-year overall survival (OS) rate of 99.2% and a five-year OS rate of 95.6%. The gradually decreased usage and shortened duration of tamixofen treatment, as well as reduced DFS and OS rates were observed in a 'real world' clinical setting. Improved treatment compliance in patients is recommended. PMID- 26136962 TI - Coxsackievirus A16 infection stimulates imbalances of T cells in children. AB - Immune reaction plays a crucial role in the regulation of the progression of Coxsackievirus A16 (CA16)-infected hand, foot and mouth disease (HFMD). However, no details of T-cell subset frequency or imbalance during the CA16 infection process have been revealed. In the present study, whether CA16-induced HFMD changes the frequency of different T-cell subsets and associated immune mediators was determined in children. The results indicate that the percentages of Th1 and Tc1 cells were significantly increased in children with HFMD compared with those in healthy children. In addition, the Th1/Th2 ratio and interferon (IFN)-gamma levels were significant higher in children with HFMD. Furthermore, the percentage of Th17 cells and the Th17/Treg ratio as well as interleukin (IL)-17A levels were higher in HFMD cases. In conclusion, the present study demonstrated the dysregulation of T-cell subsets following CA16 infection. The Th1/Th2 and Th17/Treg ratios were imbalanced following infection. Also, the imbalance Th1/Th2 and Th17/Treg ratios contributed to the increased levels of IFN-gamma and IL-17A. Based on this information, the present study provides new insights for the future study of CA16-induced HFMD and offers new data of diagnostic and therapeutic value for CA16 infection. PMID- 26136963 TI - Effects of basal insulin application on serum visfatin and adiponectin levels in type 2 diabetes. AB - The aim of this study was to investigate the effects of basal insulin application on the serum visfatin and adiponectin (APN) levels of patients with type 2 diabetes mellitus (T2DM). A total of 200 patients with T2DM, who were diagnosed in The Third People's Hospital of Jinan (glycosylated hemoglobin >=7%), were randomly divided into treatment and control groups. The patients used only oral hypoglycemic drugs and had never received insulin therapy. In the treatment group, basal insulin was administered in combination with the original application of oral hypoglycemic drugs, whereas the control group maintained the original use of oral hypoglycemic drugs or took other oral hypoglycemic agents. The body mass index and fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, visfatin, APN and blood lipid levels of the patients were examined prior to the treatment and six months later. The drug and insulin doses in the treatment group were adjusted according to the patients' blood glucose, which allowed the fasting and postprandial blood glucose levels to attain the standards. The fasting and postprandial blood glucose levels in the control group also achieved the standards. It was found that the six-month application of basal insulin could significantly decrease the glycosylated hemoglobin and significantly increase the serum APN levels; the serum visfatin levels, however, remained unchanged. The immediate application of basal insulin could facilitate the attainment of glycosylated hemoglobin standards in T2DM and could increase the plasma APN levels, preventing diabetic vascular complications. PMID- 26136964 TI - Effect of the angiotensin II receptor blocker valsartan on cardiac hypertrophy and myocardial histone deacetylase expression in rats with aortic constriction. AB - The aim of the present study was to observe the myocardial expression of members of the histone deacetylase (HDAC) family (HDAC2, HDAC5 and HDAC9) in rats with or without myocardial hypertrophy (MH) in the presence and absence of the angiotensin II receptor blocker valsartan. Adult male Wistar rats were randomly divided into three groups (n=6/group): Sham-operated control rats, treated with distilled water (1 ml/day) through gavage; rats with MH (established through aortic constriction), treated with distilled water (1 ml/day) through gavage; and MH + valsartan rats, treated with 20 mg/kg/day valsartan through gavage. Treatments commenced one day after surgery and continued for eight weeks. Body weight (BW), heart weight (HW) and plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were determined, and the myocardial expression of HDAC2, HDAC5 and HDAC9 was analyzed through a reverse transcription semi-quantitative polymerase chain reaction. The BWs of the rats in the three groups were similar at baseline; however, after eight weeks the BW of the rats in the MH + valsartan group was significantly reduced compared with that of the MH rats. Furthermore, the HW/BW ratio and plasma ANP and BNP levels were increased, the myocardial HDAC2 expression was significantly upregulated and the HDAC5 and HDAC9 expression was significantly downregulated in the MH rats compared with those in the control rats; however, these changes were significantly attenuated by valsartan. Modulation of myocardial HDAC5, HDAC9 and HDAC2 expression may therefore be one of the anti-hypertrophic mechanisms of valsartan in this rat MH model. PMID- 26136965 TI - Magnetic resonance imaging-navigated argon-helium cryoablation therapy against a rabbit VX2 brain tumor. AB - The aim of the present study was to investigate the feasibility of interventional magnetic resonance imaging (MRI)-guided and monitored argon-helium cryoablation for the treatment of brain tumors in rabbits. In addition, the present study evaluated the associations between imaging and pathology, the therapeutic effects and the effects on the surrounding normal tissues. A total of 14 rabbits were equally divided into groups C and D. Under general anesthesia, the skull was drilled and tumor blocks were implanted. Subsequently, a New Zealand rabbit VX2 brain tumor model was successfully established. Rabbits in group C were treated with argon-helium cryoablation and those in group D did not undergo any treatment (control). Regular postoperative MRI scanning was performed to observe the changes in tumor size, and the survival times of the rabbits in groups C and D were recorded. The extent of necrosis in the brain tumor exhibited a significant correlation with the freezing time of cryoablation, and the necrotic region was shown to be the same size as the ice ball. The survival times of the rabbits in the treatment group (group C) were significantly prolonged. Therefore, the observations of the present study demonstrated that the VX2 brain tumor model, produced using an improved tumor block implantation method, was stable and suitable for MRI observation and interventional study. In addition, argon-helium cryoablation was shown to be a safe and feasible therapeutic method for the treatment of brain tumors, and was demonstrated to significantly increase the survival times of the brain tumor-bearing rabbits. PMID- 26136966 TI - Association study of three single-nucleotide polymorphisms in the cyclic adenosine monophosphate response element binding 1 gene and major depressive disorder. AB - Major depressive disorder is a common chronic emotional disorder, and cyclic adenosine monophosphate response element binding protein 1 (CREB1) is hypothesized to play a role in its pathogenesis. The aim of the present study was to investigate the associations between major depressive disorder and relevant single nucleotide polymorphisms (SNPs) in the CREB1 gene. A total of 1,038 subjects of Han Chinese descent were recruited, including 456 patients with major depressive disorder (case group) and 582 healthy volunteers (control group). The frequency distributions of the genotypes and alleles were estimated in the case and control groups, and analyzed for any correlation with major depressive disorder. Three relevant SNP sites in CREB1 were analyzed using quantitative polymerase chain reaction, and statistical analyses were performed to estimate their use as risk factors for major depressive disorder. The analyses revealed that rs2254137 and rs16839883 in CREB1 showed polymorphisms in the sample population, and the genotype and allele frequencies of rs16839883 differed significantly when comparing the patients and healthy controls (P<0.05). No statistically significant differences were detected in the two SNP sites between the male and female patients (P>0.05). Furthermore, no statistically significant differences were detected in rs2254137 genotype and allele distribution when comparing the male and female patients with their corresponding control groups (P>0.05). However, statistically significant differences were observed in the genotype and allele frequencies of rs16839883 when the male and female patients were compared with their respective controls (P<0.05). Therefore, the results demonstrated that there is a close correlation between the rs16839883 polymorphism in CREB1 and major depressive disorder, which suggests that this SNP site should be further studied as a potential biomarker for major depressive disorder. PMID- 26136967 TI - Thoracoscopy-assisted first rib resection for the treatment of thoracic outlet syndrome caused by fibrous dysplasia: A report of two cases. AB - This study reports two rare cases of thoracic outlet syndrome (TOS) caused by fibrous dysplasia of the first rib. Two patients, aged 19 and 29 years old, were admitted with TOS in the lower trunk of the brachial plexus caused by an inflated first rib. In these two cases symptoms included hypoesthesia of the anterior medial aspect of the forearm and two fingers in the ulnar side, and progressive weakness of the upper limbs. Surgery was required to resect the first rib. Transaxillary and supraclavicular excisions were challenging to perform due to the involvement of the subclavian vasculature and brachial plexus. Thoracoscopy was used in these cases in order to peel the pleura off the first rib and facilitate resection by the supraclavicular approach. None of the patients exhibited nerve or vascular complications following the surgery. PMID- 26136968 TI - Effect of elastin-derived peptides on the production of tissue inhibitor of metalloproteinase-1, -2, and -3 and the ratios in various endothelial cell lines. AB - Tissue inhibitors of metalloproteinases (TIMPs) control the activity of metalloproteinases. Elastin-derived peptides (EDPs) are generated as a result of the degradation of elastin fibers. The EDPs bind to the elastin receptor and exert numerous biological effects. The aim of the present study was to compare the production of TIMP-1, TIMP-2 and TIMP-3 and their ratios in human endothelial cells (ECs) derived from three clinically important vascular localizations (coronary arteries, aorta and iliac artery), and evaluate the influence of a well known EDP, kappa-elastin. The highest concentration of TIMP-1 was identified in the aortic ECs, while the lowest concentration was observed in the ECs derived from the coronary artery. The opposite pattern was observed for TIMP-2 production. When the TIMP-3 concentration was analyzed in the three EC lines, no statistically significant differences were observed. Application of kappa-elastin was found to decrease the TIMP-1 concentration in the aortic ECs, while an increase in the TIMP-1 concentration was observed in the ECs derived from the iliac artery. The most significant decrease in TIMP-2 concentration following kappa-elastin administration was observed in the ECs obtained from the coronary arteries. Furthermore, the highest concentration of kappa-elastin resulted in an increase in TIMP-3 production in the ECs derived from the coronary arteries. The following ratios of the TIMP concentrations were calculated: TIMP-1/TIMP-2, TIMP 1/TIMP-3 and TIMP-2/TIMP-3. Each ratio presented different values for the ECs obtained from the various localizations. In the majority of cases, the addition of kappa-elastin did not significantly change these proportions. Therefore, these indicators may be characteristic features that can be used to describe ECs in various clinically important vascular localizations. PMID- 26136969 TI - Efficacy and safety of nucleoside analogs on blocking father-to-infant vertical transmission of hepatitis B virus. AB - The aim of the present study was to observe the efficacy and safety of nucleoside analogs in inhibiting father-to-infant vertical transmission of hepatitis B virus (HBV). Nucleoside analogs compete with HBV DNA polymerase substrate to inhibit DNA polymerase, thus preventing the replication of HBV DNA. A case group and control group were recruited for the study. Between March 2006 and March 2012 at the Liver Disease Center of Qinhuangdao Third Hospital, a total of 201 couples were recruited for the case group. In each case, the father tested positive the following HBV markers: Hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), antibodies against the hepatitis B core antigen (anti-HBc) and HBV DNA. In total, 189 male patients presented with abnormal liver function (94.0%; 189/201). Prior to pregnancy, all the males in the case group were required to test negative for HBV DNA and exhibit normal liver function, while the females were required to test positive for antibodies against HBsAg (anti-HBs). In total, 188 couples comprised the control group. The couples were recruited between March 2006 and March 2012 in the Prenatal Clinic of Qinhuangdao Women's and Children's Hospital. The fathers tested positive for HBsAg, HBeAg, anti-HBc and HBV DNA. With regard to the females, HBsAg tests were all negative and anti-HBs tests were positive. In the case group, there were no HBsAg-positive or HBV DNA-positive newborns, while anti-HBs tests were all positive; thus, the father-to-infant HBV vertical transmission was successfully inhibited. In the control group, 147/188 newborns tested positive for anti-HBs at birth, accounting for 78.2%. In addition, 28 newborns were positive for HBV DNA (14.9%), and 19 newborns tested positive for HBsAg (10.1%). Statistically significant differences were observed between the two groups with regard to these parameters. However, no statistically significant differences in gestational age, birth weight, birth height, 1- and 8 min Apgar scores, presence of jaundice, other internal and surgical diseases, delivery mode and other birth information were observed when comparing the case group with the control group. Furthermore, there were no fetal malformations or stillbirths in the two groups. In the HBV DNA-positive fathers prior to pregnancy, antiretroviral therapy resulted in a reduced virus load. Therefore, blocking father-to-infant HBV vertical transmission maximally was important. The use of antiviral nucleoside analogs prior to pregnancy was shown to be safe. When the benefits outweighed the risks, the fathers who wanted to have a child continued to use antiviral therapy. However, the sample size of the present study was small, and an increased number of cases and longer follow-up times are required. In addition, the use of nucleoside analogs requires further in-depth assessment from the point of view of prenatal and postnatal care. PMID- 26136970 TI - Platelet-derived miR-92a downregulates cysteine protease inhibitor cystatin C in type II diabetic lower limb ischemia. AB - The aim of the present study was to investigate the effect of microRNA (miR)-92a on cystatin C expression in patients with type II diabetes and lower limb ischemia. A total of 199 patients diagnosed with type II diabetes were included in the study and divided into three experimental groups: Simple type II diabetes mellitus (T2DM; n=60) group; type II diabetes with light to moderate occlusion (LLI-LM; n=70) group; and the type II diabetes with severe occlusion (LLI-S; n=69) group according to the patient ankle-brachial index score. In addition, 60 healthy individuals were examined as a control population. The expression levels of various biochemical indices were detected, including cystatin C in the peripheral blood. The expression levels of miR-92a and cystatin C mRNA were detected by reverse transcription-quantitative polymerase chain reaction (RT qPCR) and the correlation between miR-92a, cystatin C and the pathological development of type II diabetic lower limb ischemia was analyzed. The protein expression levels of cystatin C were detected using western blot analysis. Bioinformatic analysis indicated that miR-92a was able to downregulate cystatin C expression, and this result was supported by endothelial cell transfection. In the transfection assay, an miR-92a mimic downregulated cystatin C expression, while an miR-92a inhibitor upregulated cystatin C expression. The results of the RT-qPCR indicated that the expression levels of miR-92a in the LLI-S group were reduced compared with those in the T2DM and LLI-LM groups, and significantly lower compared with those in the negative control group. Platelet-derived miR-92a appeared to downregulate cystatin C expression in patients with type II diabetes and lower limb ischemia. Therefore, the combined detection of miR-92a and cystatin C may be useful as a method for clinically screening patients with type II diabetes for lower limb ischemia. PMID- 26136971 TI - Corticosteroid versus placebo injection for plantar fasciitis: A meta-analysis of randomized controlled trials. AB - The aim of this meta-analysis was to determine the efficacy of corticosteroid versus placebo injection for the treatment of plantar fasciitis. Databases (Medline, Embase, the Cochrane Library and Google Scholar) and study references were searched for randomized controlled trials comparing corticosteroid with placebo injection for plantar fasciitis. Studies that met the inclusion criteria were selected for the analysis. The risk of bias tool was used for the methodological assessment. Outcomes including visual analogue score (VAS) and plantar fascia thickness (PFT) were extracted and pooled. Egger's test was used to detect publication bias. The evidence quality was assessed by the Grading of Recommendations Assessment, Development and Evaluation system. Statistical analysis was performed using RevMan 5.2. A total of four studies with 289 patients were included in the analysis. Compared with the placebo, corticosteroid injection provided better pain relief after one month [standardized mean difference (SMD), -0.32; 95% confidence interval (CI), -0.59--0.06); P=0.02). No difference was detected with respect to the VAS after two months (SMD, -0.04; 95% CI, -0.35-0.27; P=0.79) or three months (SMD, -0.42; 95% CI, -1.00-0.16; P=0.15) or to the PFT (MD, 0.70; 95% CI, -1.77-0.38; P=0.20), although a tendency of favoring corticosteroid injection was observed. No obvious publication bias was detected. In conclusion, corticosteroid injection may provide pain relief for a short period of time, but the efficacy may disappear with the progression of time. PMID- 26136972 TI - Two one-stage posterior approaches for treating thoracic and lumbar spinal tuberculosis: A retrospective case-control study. AB - The aim of this retrospective study was to analyze the results of two surgical treatments for thoracic and lumbar spinal tuberculosis. A total of 73 patients with monosegmental thoracic or lumbar spinal tuberculosis were enrolled from January 2006 to April 2011. The patients were divided into two groups. Patients in group A (n=34) underwent one-stage posterior debridement, limited decompression, bone grafting and internal fixation combined with lamina reconstruction, while those in group B (n=39) underwent one-stage posterior debridement, decompression, bone grafting and posterior instrumentation. Clinical and radiographic results were analyzed and compared between the groups. Patients were followed for a mean 31.3 months (range, 21-42 months). Fusion occurred at 4 12 months (mean, 7.7 months). Surgical complications affected one and five patients in groups A and B, respectively. There was extraction of internal fixation in two group B patients. Postoperatively, there was significant Cobb angle correction in the two groups. By the last follow-up, the Cobb angle and correction loss in group A were significantly better than that in group B; the group A Oswestry Disability Index and Frankel grade were better than that in group B. In conclusion, one-stage posterior limited decompression, bone grafting and internal fixation combined with lamina reconstruction enables rapid management of monosegmental thoracic and lumbar spinal tuberculosis with fewer complications and minimal invasion. PMID- 26136973 TI - Therapeutic effects and associated adverse events of multikinase inhibitors in metastatic renal cell carcinoma: A meta-analysis. AB - This study aimed to compare the therapeutic effects and adverse events of the multikinase inhibitors sorafenib, sunitinib, pazopanib and axitinib in advanced renal cell carcinoma (RCC). A meta-analysis of randomized controlled trials was performed to assess the effects of multikinase inhibitors among patients with advanced RCC. The data of median progression-free survival (PFS), median overall survival (OS), progressive disease rate (PDR), objective response rate (ORR) and grade 3/4 adverse events were extracted to assess therapeutic effects and toxicity, respectively. It was found that multikinase inhibitors are more effective in extending PFS [hazard ratio (HR)=0.58; 95% confidence interval (CI): 0.45-0.74; P<0.0001), controlling tumor progression [relative risk (RR)=0.67; 95% CI: 0.55-0.83; P=0.0002) and ORR (RR=2.93; 95% CI: 1.40-6.14; P=0.004) compared with placebo or interferon-alpha. Patients treated with multikinase inhibitors had significantly higher rates of grade 3 or 4 hypertension (RR=6.00; 95% CI: 3.36-10.69; P<0.00001), diarrhea (RR=5.84; 95% CI: 3.06-11.16; P<0.00001), nausea (RR=2.30; 95% CI: 1.16-4.54; P=0.02), vomiting (RR=1.84; 95% CI: 1.00-3.41; P=0.05) and hand-foot skin reaction (RR=11.78; 95% CI: 5.16-26.93; P<0.00001). Multikinase inhibitors can significantly control disease progress and improve the ORR. However, they are also associated with a higher risk of grade 3 and 4 hypertension and gastrointestinal events. Proper management of these events is necessary to improve patient quality of life. PMID- 26136974 TI - Importance of risk factors for the evaluation of patients with a suspected pulmonary embolism. AB - The reliable exclusion of a pulmonary embolism (PE) in hemodynamically stable patients remains a challenge. The European Society of Cardiology guidelines for PE diagnosis published in 2008 and updated in 2014 recommend a low-threshold computed tomography (CT) indication for patients with a high probability of pulmonary embolism or those with elevated levels of D-dimers. Certain elements of the recommendations are controversial, while others, including the evaluation of the risk factors for PE, are considered only in individual cases. In the present study, various risk factors, including obesity, smoking, contraceptive use, immobility level, history of malignant disease and thrombophilia and the factors of familial predisposition, deep vein thrombosis (DVT)/PE-history, long-distance flying <1 week and surgery <4 weeks previously, were retrospectively examined in 492 patients with a suspected PE. The data demonstrated a significant risk of PE with contraceptive use, a history of DVT/PE and thrombophilia. The immobility level, surgery <4 weeks and long-distance flying <1 week previously, as well as family history, malignant disease, obesity and smoking, were not observed to be associated with a significantly higher risk of PE. Contraceptive use and thrombophilia, in addition to a history of DVT/PE, each appear to have a significant predictive value in the context of PE risk stratification. Therefore, patients with a suspected PE, who additionally present with at least one of the aforementioned risk factors, should undergo further diagnostic steps for PE risk stratification, including a low-threshold CT examination, even in the absence of elevated D-dimers. PMID- 26136975 TI - Paclitaxel-coated balloons for the treatment of patients with in-stent restenosis: A meta-analysis of angiographic and clinical data. AB - Paclitaxel-coated balloons (PCBs) have become attractive alternative treatment options for patients with in-stent restenosis (ISR); however, the safety and efficacy of PCBs in comparison with those of conventional therapies are less well defined. The aim of this meta-analysis was to systematically review the efficacy and safety of PCBs for patients with ISR using comparisons with control groups. Electronic databases, such as MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, were searched, and eligible studies that compared PCBs with uncoated balloons (UCBs) or drug-eluting stents (DESs) in patients with ISR were considered. Subgroup analyses were performed with different control groups. Nine studies (1,488 patients, 1,608 lesions) were included in the meta-analysis. Compared with patients who underwent UCB angioplasty, those who underwent PCB angioplasty exhibited a clear superiority in late lumen loss (LLL) [weighted mean difference (WMD), -0.46; 95% confidence interval (CI), (-0.59)-(-0.34); P<0.00001] and major adverse cardiac events (MACEs) [odds ratio (OR), 0.21; 95% CI, 0.13-0.33; P<0.00001]. The OR for myocardial infarction (MI) (OR, 0.46; 95% CI, 0.15-1.47; P=0.19) did not reach statistical significance. PCBs were associated with similar outcomes when compared with DESs with regard to LLL (WMD, -0.04; 95% CI, -0.18-0.10; P=0.57), MACEs (OR, 0.74; 95% CI, 0.36-1.53; P=0.42) and the ORs for all endpoints, including total mortality, target lesion revascularization, MI, stent thrombosis and binary restenosis, and no statistically significant differences were found. This meta-analysis showed that PCBs are associated with superior outcomes when compared with UCBs in the management of ISR, and are at least as efficacious and as well tolerated as DESs. PMID- 26136976 TI - A comparison of the effects of midazolam, propofol and dexmedetomidine on the antioxidant system: A randomized trial. AB - Previous studies on the antioxidant activity of sedatives have predominantly been in vitro investigations that are lacking clinical data, resulting in conclusion without cogency. The aim of the present prospective, randomized study was to use single sedative drugs for anesthesia induction to compare their antioxidant properties. The effects on the antioxidant system of midazolam, propofol and dexmedetomidine were assessed using oxidative stress indicators and micronuclei (MN). Forty-nine patients undergoing esophageal cancer radical prostatectomy were selected. Midazolam, propofol and dexmedetomidine were used to induce anesthesia. Venous blood samples were obtained prior to and at 2 and at 24 h after surgery, and oxidative stress indicators were detected using the appropriate kits. The cytokinesis-block micronucleus cytome assay was executed and the frequencies of MN, nucleoplasmic bridges and nuclear buds were examined. It was found that the use of the three sedatives, respectively, led to a marked increase in the levels of free radical indicators at 2 h after surgery, which then decreased at 24 h after surgery. Furthermore, lower levels of oxidative stress were found following the use of propofol and dexmedetomidine compared with those following midazolam administration, and similar results were obtained regarding the level of MN. It is suggested that propofol and dexmedetomidine exhibit a superior antioxidant function to midazolam. PMID- 26136977 TI - Multifocal osteoarticular tuberculosis of the extremities in an immunocompetent young man without pulmonary disease: A case report. AB - Osteoarticular tuberculosis (TB), an uncommon form of extrapulmonary TB, is a universal mimicker and thus represents a potential differential diagnosis of any osteolytic lesion. The present study describes a case of multifocal osteoarticular TB in an immunocompetent young man who presented with swelling and extremity pain. The patient underwent plain radiography, bone scan and magnetic resonance imaging. A diagnosis was ultimately made based on the pathology results from his second left toe. The patient responded well to anti-TB medication. The radiological findings of multifocal osteoarticular TB are described in this report. To the best of our knowledge, this is the first reported case of multifocal osteoarticular TB symmetrically affecting all the extremities. PMID- 26136978 TI - Resveratrol suppresses TGF-beta-induced VEGF synthesis in osteoblasts: Inhibition of the p44/p42 MAPKs and SAPK/JNK pathways. AB - Resveratrol, which is found in grape and berry skins and red wine, is generally known to be beneficial for human health due to its anti-inflammation and antioxidant effects. We have recently reported that transforming growth factor beta (TGF-beta) stimulates vascular endothelial growth factor (VEGF) synthesis through Smad-independent pathways, such as the p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase and stress-activated protein kinase/c-Jun N terminal kinase (SAPK/JNK) pathways, in osteoblast-like MC3T3-E1 cells. The aim of the present study was to investigate the effect of resveratrol on the TGF-beta induced VEGF synthesis and the mechanism in osteoblast-like MC3T3-E1 cells. Resveratrol significantly suppressed the TGF-beta-stimulated release of VEGF and the VEGF mRNA expression levels. SRT1720, a synthetic sirtuin 1 (SIRT1) activator, also reduced the VEGF release and the mRNA levels. With regard to the intracellular signaling in the TGF-beta-stimulated VEGF synthesis, resveratrol and SRT1720 significantly attenuated the phosphorylation of p44/p42 MAP kinase and SAPK/JNK stimulated by TGF-beta; however, the TGF-beta-induced phosphorylation of Smad2 and p38 MAP kinase was hardly affected by resveratrol or SRT1720. These results strongly suggest that the TGF-beta-stimulated VEGF synthesis is suppressed by resveratrol through the inhibition of p44/p42 MAP kinase and SAPK/JNK in osteoblasts, and that the suppressive effect is mediated, at least in part, via SIRT1 activation. PMID- 26136979 TI - Molecular cloning and expression of the calmodulin gene from guinea pig hearts. AB - The aim of the present study was to isolate and characterize a complementary DNA (cDNA) clone encoding the calmodulin (CaM; GenBank accession no. FJ012165) gene from guinea pig hearts. The CaM gene was amplified from cDNA collected from guinea pig hearts and inserted into a pGEM(r)-T Easy vector. Subsequently, CaM nucleotide and protein sequence similarity analysis was conducted between guinea pigs and other species. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to investigate the CaM 3 expression patterns in different guinea pig tissues. Sequence analysis revealed that the CaM gene isolated from the guinea pig heart had ~90% sequence identity with the CaM 3 genes in humans, mice and rats. Furthermore, the deduced peptide sequences of CaM 3 in the guinea pig showed 100% homology to the CaM proteins from other species. In addition, the RT-PCR results indicated that CaM 3 was widely and differentially expressed in guinea pigs. In conclusion, the current study provided valuable information with regard to the cloning and expression of CaM 3 in guinea pig hearts. These findings may be helpful for understanding the function of CaM3 and the possible role of CaM3 in cardiovascular diseases. PMID- 26136980 TI - Genome-wide analysis of androgen receptor binding sites in prostate cancer cells. AB - The transformation of prostate cancer from an androgen-dependent state to an androgen-independent state is a lethal progression. Alterations in transcriptional programs are the basis of prostate cancer deterioration. The androgen receptor (AR), a member of the nuclear hormone receptor superfamily, mediates prostate cancer progression by functioning primarily through the ligand activated transcription of target genes. Therefore, a detailed map of AR regulated genes and AR genomic binding sites is required for hormone-naive and castration-resistant prostate cancer. Through the use of chromatin immunoprecipitation in combination with direct sequencing, 4,143 AR binding sites were defined in the LNCaP androgen-sensitive prostate cancer cell line. Using the same method, 2,380 AR binding regions were identified in the LNCaP-AI long-term androgen-deprived cell line. Approximately 8.5% (354/4,143) of the binding regions were mapped to within 2 kb of the transcription start site (TSS) in the LNCaP cells, while ~12.6% (299/2,380) were mapped to within 2 kb of the TSS in the LNCaP-AI cells. In total, the study mapped 2,796 genes in LNCaP cells and 1,854 genes in LNCaP-AI cells. The cell lines shared 789 mutual genes. In addition, gene ontology (GO) analysis of the genes revealed that there was a notable overlap between the GO terms in the LNCaP cells and LNCaP-AI cells. However, GO terms within the biological process domain that were only observed in the LNCaP-AI cells included the reproduction process, death, immune system process, multi-organism process, pigmentation and viral reproduction. The major genes in the different GO terms were TNFAIP8, RTN4, APP and SYNE1. Through analyzing the AR binding sites in the two cell types, the present study aimed to map potential AR-regulated genes, identify their associated transcription factors and provide a new perspective on the biological processes in the development of prostate cancer. The results provided a valuable data set that furthered the understanding of the genome-wide analysis of AR binding sites in prostate cancer cells, which may be exploited for the development of novel prostate cancer therapeutic strategies. PMID- 26136981 TI - Association of gene polymorphisms in ABO blood group chromosomal regions and menstrual disorders. AB - This study aimed to investigate whether single nucleotide polymorphisms (SNPs) located near the gene of the ABO blood group play an important role in the genetic aetiology of menstrual disorders (MDs). Polymerase chain reaction-ligase detection reaction technology was used to detect eight SNPs near the ABO gene location on the chromosomes in 250 cases of MD and 250 cases of normal menstruation. The differences in the distribution of each genotype, as well as the allele frequency in the normal and control groups, were analysed using Pearson's chi2 test to search for disease-associated loci. SHEsis software was used to analyse the linkage disequilibrium and haplotype frequencies and to inspect the correlation between haplotypes and the disease. Compared with the control group, the experimental group exhibited statistically significant differences in the genotype distribution frequencies of the rs657152 locus of the ABO blood group gene and the rs17250673 locus of the tumour necrosis factor cofactor 2 (TRAF2) gene, which is located downstream of the ABO gene. The allele distribution frequencies of rs657152 and rs495828 loci in the ABO blood group gene exhibited significant differences between the groups. Dominant and recessive genetic model analysis of each locus revealed that the experimental group exhibited statistically significant differences from the control group in the genotype distribution frequencies of rs657152 and rs495828 loci, respectively. These results indicate that the ABO blood group gene and TRAF2 gene may be a cause of MDs. PMID- 26136982 TI - Correlation between serum levels of C-reactive protein and infant pneumonia: A meta-analysis. AB - Experimental data imply that serum C-reactive protein (CRP) is a marker of general systemic inflammation, and inflammation may have a role in the development of pneumonia. The aim of the present study was to investigate the associations of serum CRP levels in infant patients with pneumonia by meta analysis. The Science Citation Index, Cochrane Library, PubMed, Embase, CINAHL, Current Contents and two Chinese (CMB and CNKI) databases were searched. Studies were pooled and standard mean difference (SMD) and the corresponding 95% confidence interval (CI) were calculated. Subgroup analyses and publication bias detection were also conducted. The statistical analysis was conducted using Stata software version 12.0. Serum CRP levels were analyzed in 10 clinical case-control studies (652 infants with pneumonia and 845 healthy controls); significant differences in serum CRP levels were observed between infants with pneumonia and the healthy controls (SMD=4.41, 95% CI: 3.34-5.47, P<0.001). Ethnicity-stratified subgroup analysis detected that high levels of serum CRP may be the main risk factor for infant pneumonia in Asian, African and Caucasian populations (all P<0.05). Serum CRP levels were statistically higher in infants with pneumonia than in healthy infants, and thus serum levels of CRP may have independent diagnostic value for pneumonia in children. PMID- 26136983 TI - Comparison between the clot-protecting activity of a mutant plasminogen activator inhibitor-1 with a very long half-life and 6-aminocaproic acid. AB - Plasminogen activator inhibitor (PAI)-1 is a serpin glycoprotein that can stabilize blood clots by inhibiting fibrinolysis. However, wild-type PAI-1 has the disadvantage of a short half-life of ~2 h. A very long half-life (VLHL) PAI-1 mutant was developed previously with an active-form half-life of >700 h, making it a possible candidate for use in hemorrhagic therapy. Current treatments for mitigating hemorrhage, other than inducers of blood clotting, are limited to lysine analog antifibrinolytics, including 6-aminocaproic acid and tranexamic acid. VLHL PAI-1 has been previously demonstrated to limit bleeding; however, the efficacy of this protein compared with lysine analog antifibrinolytics has not been investigated. The aim of the current study was to compare the clot stabilizing properties of the novel antifibrinolytic VLHL PAI-1 with those of 6 aminocaproic acid in reference plasma. Using thromboelastographic analysis, VLHL PAI-1 exhibited an IC50 (half maximal inhibitory concentration) of 8.8*10-8 mol/l, while 6-aminocaproic acid showed an IC50 of 1.6*10-4 mol/l. However, at doses of >9.0*10-7 mol/l, VLHL PAI-1 exhibited a delay in the onset of clot formation, which may be attributed to thrombin inhibition by excess PAI-1. The inhibition of tissue plasminogen activator by VLHL PAI-1 demonstrated improved efficacy over 6-aminocaproic acid in mitigating hemorrhage. In addition, patients with a PAI-1 deficiency, which causes blood clots to lyse rapidly resulting in profuse bleeding, may benefit from the application of VLHL PAI-1 as an antihemorrhagic therapy. PMID- 26136984 TI - Analgesic roles of peripheral intrinsic met-enkephalin and dynorphin A in long lasting inflammatory pain induced by complete Freund's adjuvant in rats. AB - Previous studies have focused on strategies for pain relief based on the peripheral opioid system. However, little is known with regard to the profile of the peripheral opioid system in long-lasting inflammatory pain. In the current study, the intrinsic changes of the peripheral opioids were investigated in long lasting inflammatory pain. A rat model of complete Freund's adjuvant (CFA) induced inflammatory pain was established. Paw swelling and thermal hyperalgesia (paw withdrawal latency, PWL) were analyzed until day 18 after the CFA injection. The levels of peripheral opioids and their upstream inducers, corticotrophin releasing factor (CRF) and interleukin (IL)-1beta, were measured, and validation experiments were performed using opioid receptor antagonists. Long-lasting inflammatory pain was successfully induced in the rats, as shown by the significantly increased paw swelling and decreased PWLs. On day 18 after the CFA injection, the IL-1beta levels were significantly elevated, while CRF remained at a normal level in the paw inflammatory tissue. In addition, met-enkephalin (Met ENK) and dynorphin A (DYN A) levels were significantly increased, while the beta endorphin level remained normal. Local intraplantar administration of delta- and kappa-opioid receptor antagonists resulted in more substantial pain, but did not significantly affect the PWLs of the normal control rats. Therefore, the results indicated that the increased levels of local Met-ENK and DYN A in CFA-induced long-lasting inflammatory pain may be involved in peripheral intrinsic analgesia. PMID- 26136986 TI - Coexisting renal cell carcinoma and renal artery aneurysm: A case report and literature review. AB - Renal artery aneurysms (RAAs) are a rare condition; however, the coexistence of an RAA with renal cell carcinoma (RCC) is extremely rare. The present study reports the case of a patient found to simultaneously have an operable RAA and RCC. The patient was treated by radical nephrectomy. Surgical intervention for RAA is controversial, and the appropriate treatment for RCC with RAA has not been well characterized and requires further study. The present study reports the examination of a patient with coexisting RAA and RCC and suggests possible treatments for this condition. In addition, a review of the English literature investigating the association of RCC with RAA is presented. PMID- 26136985 TI - Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats. AB - Jia-Yuan-Qing pill (JYQP) composed of Porcellio laevis Latreille, Corydalis Rhizoma and Radix Cynanchi Paniculati at a ratio of 9:7:7 has been found to be an effective analgesic agent. The present study aimed to evaluate the safety, addictive potential and anti-cancer pain activity of JYQP in a rat model. During the 6-month chronic toxicity test, no significant changes in general behavior, defecation, postural abnormalities, dietary or water intake or blood biochemical parameters were observed in male and female rats. Although a high dose of JYQP (5 g/kg) caused swelling of the liver, spleen and kidney in male and female rats, no pathological changes were observed in all organs examined via hematoxylin and eosin staining. The analgesic effect of JYQP on bone cancer pain was successfully confirmed in a rat model of Walker 256 cell-induced bone cancer. In contrast to morphine, in a physical dependence test, JYQP produced no withdrawal symptoms following chronic administration. The data from this study provide experimental evidence supporting the clinical use of JYQP as an effective, safe and non addictive agent for the treatment of bone cancer pain. PMID- 26136987 TI - Hybrid technique to treat superior mesenteric artery occlusion in patients with acute mesenteric ischemia. AB - Acute mesenteric ischemia is a condition with a high mortality rate. In the present study, a novel hybrid technique for the treatment of acute mesenteric ischemia was investigated. The retrospective study population included six patients, of which five were male and one was female, with a mean age of 69 years (age range, 59-73 years). The hybrid technique involved isolating the superior mesenteric artery (SMA) for cannulation and subsequently performing a fluoroscopically-assisted embolectomy, retrograde balloon angioplasty and stenting. Intra-arterial, catheter-directed thrombolysis was performed if required. Bowels showing evident necrosis were resected, while ischemic bowels with the potential for recovery were left for 48 h before being re-examined during the second-look surgery. Retrograde open mesenteric stenting (ROMS) was successfully performed on two patients without bowel resection. Four patients were successfully treated by intra-arterial catheter-directed thrombolysis following recanalization of the SMA, and the ischemic bowels had exhibited a full recovery by the second-look operation. Three patients underwent a massive bowel resection, but did not develop short bowel syndrome. Two patients developed acute renal failure, one of which recovered after 10 days of dialysis, while the other patient succumbed to acute renal failure. In the five surviving patients, the SMA remained patent for the duration of the follow-up period. Therefore, ROMS was shown to be a viable alternative procedure for emergent SMA revascularization. In addition, intra-arterial catheter-directed thrombolysis following recanalization of the SMA was demonstrated as an alternative technique for inhibiting necrosis in bowels with acute mesenteric ischemia. PMID- 26136988 TI - Effect of Helicobacter pylori on cyclooxygenase-2 and inducible nitric oxide synthase in patients with gastric precancerous lesions and its clinical significance. AB - The aim of this study was to investigate the effect of Helicobacter pylori (Hp) on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) levels in patients with gastric precancerous lesions and its clinical significance. A total of 114 patients with gastric precancerous lesions, 57 whom were positive for Hp (observation group) and 57 of whom were negative for Hp (control group), were selected for the study. The mRNA levels of COX-2 and iNOS in the gastric precancerous lesion tissue from the two groups of patients were analyzed through the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein expression levels of COX-2 and iNOS were analyzed using western blotting and an iNOS kit, respectively. In addition, normal human gastric mucosal GES-1 cells were cultured in vitro and stimulated by Hp for 3, 6, 9 and 12 h. The variations in the mRNA and protein levels of COX-2 and iNOS were then analyzed via RT-qPCR and western blotting. Compared with the control group, the mRNA levels of COX-2 and iNOS in the gastric tissue from the observation group were significantly increased (P<0.05). Furthermore, the expression level of COX-2 and iNOS protein in the gastric tissue from the observation group was significantly higher than that in the tissue from the control group (P<0.05). In vitro analysis showed that the COX-2 and iNOS mRNA and protein levels were significantly increased in the Hp-stimulated normal human gastric mucosal GES-1 cells compared with those in the unstimulated cells. Furthermore, the effect was time-dependent (P<0.05). In conclusion, COX-2 and iNOS are the main inflammatory markers. Hp can induce high expression levels of COX-2 and iNOS in gastric precancerous lesion tissue, which may be associated with the occurrence and development of gastric precancerous lesions. PMID- 26136989 TI - Testing of kisspeptin levels in girls with idiopathic central precocious puberty and its significance. AB - The aim of this study was to explore the significance of plasma kisspeptin levels in diagnosis and therapeutic evaluation through the analysis of the kisspeptin levels of girls diagnosed with idiopathic central precocious puberty (ICPP) prior to treatment and after 6-months of treatment and those with simple premature thelarche (PT). A total of 70 girls including 24 girls diagnosed with ICPP, 21 girls with PT and 25 normal girls were enrolled in the study. ELISA analysis was conducted to detect the plasma levels of kisspeptin. The kisspeptin level of the ICPP group prior to treatment (1.80+/-0.13 ng/ml) was significantly higher than those of the other two groups. The kisspeptin level of the ICPP group after 6 months of treatment (1.49+/-0.21 ng/ml) was significantly lower than that prior to treatment (P<0.05). It may be concluded that the plasma level of kisspeptin is associated with the initiation of pubertal development, and it may serve as an important parameter in the diagnosis of ICPP and the evaluation of therapeutic effects. PMID- 26136990 TI - Expression and clinical significance of cyclooxygenase-2 and microRNA-143 in osteosarcoma. AB - The aim of the present study was to investigate the expression profiles of cyclooxygenase (COX)-2 and microRNA (miRNA)-143 in the tumor tissue and blood samples of patients with osteosarcoma, and their involvement in the disease pathogenesis. Tumor tissue and blood samples were obtained from 46 patients with osteosarcoma (stages I-III). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to detect the mRNA and protein expression of COX-2, respectively, in these samples. The expression of miRNA-143 in the tumor tissue and blood samples was assessed using RT-qPCR. The results showed that, compared with the normal control subjects, the mRNA and protein expression levels of COX-2 in the tumor tissue and blood samples of patients with osteosarcoma were increased. Among the patients with osteosarcoma, increases in the COX-2 mRNA and protein levels were observed with progressing disease severity (from stage I to stage III), suggesting the involvement of COX-2 in the disease pathogenesis. By contrast, the expression of miRNA-143 decreased as the disease progressed, which was the opposite trend to the COX-2 expression, indicating that miRNA-143 and COX-2 may play different roles in the disease pathogenesis. In conclusion, COX-2 expression in the tumor tissue and blood samples of patients with osteosarcoma increases significantly along with the degree of tumor malignancy, and this is accompanied by a decreased expression of miRNA-143; therefore, a negative correlation between COX-2 and miRNA-143 may exist in the progression of osteosarcoma. PMID- 26136991 TI - Clinical features of post-infectious bronchiolitis obliterans in children undergoing long-term azithromycin treatment. AB - The aim of the present study was to outline any predisposing factors and clinical and radiological features of post-infectious bronchiolitis obliterans (PIBO) in pediatric patients, and to determine the effect of long-term azithromycin treatment on these factors. In total, 16 cases of children with PIBO were retrospectively reviewed. Adenovirus and Mycoplasma pneumoniae were the most common etiological agents (12/16) in the children with PIBO. The patients presented with persistent dyspnea, a chronic cough, sputum production and wheezing following the initial lung infection. Chest X-rays indicated pulmonary overinflation and patchy ground-glass opacity. In addition, high-resolution computed tomography (HRCT) scans revealed patchy ground-glass opacity, bronchiectasis, bronchial wall thickening and mosaic perfusion in all 16 cases. A unilateral hyperlucent lung was observed in two cases. All the patients underwent treatment with low-dose azithromycin and prednisone. Follow-up examinations of the 16 cases, varying in duration between 7 and 31 months, showed that the disease condition had improved in 10 cases. However, no significant improvements were identified from the HRCT scans or were observed in the patient condition in the additional six cases. The diagnosis of BO is primarily based on a typical clinical presentation and HRCT observations. Therefore, a typical clinical history and patchy ground-glass opacity features on HRCT scans are screening indices that predict BO development. Steroids are the cornerstone of BO treatment; however, long-term azithromycin treatment can improve the condition of the patients. In summary, PIBO is a disease with a high morbidity rate and should be treated by a multidisciplinary team. Patients should receive follow-up examination for an extended period. Patchy ground-glass opacity features on HRCT scans indicate that clinical suspicion of BO is necessary in children with persistent and severe wheezing. PMID- 26136992 TI - Dose study of electrocardiogram automatic tube current modulation technology in prospective coronary computed tomography angiography scans of overweight patients. AB - The aim of the present study was to investigate the X-ray absorption dose and clinical applications of electrocardiogram (ECG)-gated automatic tube current modulation (ATCM) technology in prospective sequential computed tomography coronary angiography (CTCA) scans of overweight patients. A total of 40 patients with a body mass index of >24 were divided at random into groups A and B. Group A consisted of 20 patients, who were examined using ECG-ATCM scanning. For the patients in group A with heart rates <70 bpm, the scanning range was 20-80% of the R-R interval and the patients received full-dose X-rays for 60-80% of the R-R interval. For the group A patients with heart rates >70 bpm, the scanning range was 20-80% of the R-R interval and the patients received full-dose scanning for 35-55% of the R-R interval. For the 20 patients in group B, the scanning range was 20-80% of the R-R interval and patients received a full dose of X-ray radiation for the entire scanning period. The image quality and radiation dose was compared between the two groups. The average radiation dose in groups A and B was 6.91+/-2.78 and 10.43+/-3.36, respectively. The radiation doses in group A were reduced by 33.77% when compared with group B (P<0.05). However, there was no marked difference observed in image quality. In summary, using ECG-ATCM technology in prospective sequential CTCA scanning may significantly reduce the radiation dose required for overweight patients. PMID- 26136993 TI - Expression of beta-site APP-cleaving enzyme 1 in the hippocampal tissue of an insulin-resistant rat model of Alzheimer's disease. AB - The aim of this study was to investigate the expression of beta-site APP-cleaving enzyme 1 (BACE1) in the hippocampal tissue of an insulin-resistant rat model, and thereby explore the roles of BACE1 and insulin resistance (IR) in the pathogenesis of Alzheimer's disease (AD). A total of 36 male Sprague-Dawley rats, aged 2 months, were randomly divided into three groups. These were an insulin resistant (experimental) group, a high fat control group and a blank control group. The cognitive function and behavioral changes of the rats were tested by a Morris water maze experiment. Amyloid beta (Abeta) deposition was detected by an immunohistochemical method. The expression levels of BACE1 in the rat hippocampal tissues were detected by enzyme-linked immunosorbent assay, western blotting and reverse transcription-quantitative polymerase chain reaction technology. The rats in the experimental group had evident learning and memory impairment, with significantly decreased learning memory. The modeling was successful; in the experimental group, the rats exhibited IR and their glucose metabolism was significantly abnormal. However, there was no characteristic pathology of AD. The expression of BACE1 in the brain tissue of rats in the experimental group was significantly higher than that in high fat control and blank control groups (P<0.01). In conclusion, the expression of BACE1 in the brain tissue of insulin resistant rats increased, and IR was indicated to participate in the pathogenesis of AD. PMID- 26136994 TI - High plasma levels of oxidatively modified low-density lipoproteins are associated with the suppressed expression of immunomodulatory molecules in patients with hematological malignancies. AB - Dyslipidemia is a common feature in immunosuppressed patients, such as kidney and bone marrow transplantation recipients and patients with breast, prostate or gynecological carcinoma or acute lymphoblastic leukemia. In addition, high levels of oxidatively modified low-density lipoproteins (oxLDLs) are closely associated with carcinogenesis. There are, however, no reports on the association between the serum oxLDL levels and the expression of important immunomodulatory molecules in patients with hematological disorders. In the present study, 39 patients with hematological disorders were stratified into four groups: Two groups with malignancies [chronic myeloid leukemia (CML) and acute myeloblastic leukemia (AML)] and two groups without malignancies [myelodysplastic syndrome (MDS) and iron deficiency anemia (IDA)]. Immunomodulatory molecules were monitored in these groups. The enzyme-linked immunosorbent assay results indicated that the plasma oxLDL levels were significantly higher in patients with AML or CML than those in patients with MDS or IDA. The quantitative polymerase chain reaction results revealed that the expression of numerous important immunomodulatory elements, including tumor-related genes, immunological and inflammatory cytokines, defense responsive genes, genes regulating cell proliferation, adhesion and migration molecules and leukocyte chemotaxis genes, showed considerable variation in patients with hematological disorders, particularly in those with MDS or IDA, as compared with the expression in the healthy volunteers. The present study demonstrated that, in patients with a hematological malignancy (either AML or CML), the activation of numerous immune response-related molecules was inhibited. Thus, an association between hematological malignancies and dyslipidemia, i.e. high levels of oxLDL, is suggested. Further research is necessary to investigate how oxLDL influences cancer progression. PMID- 26136995 TI - Effects of different routes of tirofiban injection on the left ventricular function and prognosis of patients with myocardial infarction treated with percutaneous coronary intervention. AB - The aim of this study was to investigate the effect of different routes of tirofiban injection on the function of the left ventricle and the prognosis of patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI). Ninety-five patients with MI treated with PCI were divided into two groups [coronary (n=49) and intravenous (n=46)] according to the injection route. A comparison of the left ventricular function and prognosis was made between the two groups following PCI. The success rate of PCI in the coronary group was 97.96%, which was higher than that in the intravenous group (P<0.05). No significant differences were identified in the platelet count (PLT) and platelet aggregation rate (PAR) between the two groups prior to the tirofiban injection. Following the tirofiban injection, the PLT decreased markedly in both groups, with no significant differences between them. The PAR also decreased significantly in the two groups; however, the value in the coronary group was lower than that in the intravenous group (P<0.05). The improvements in the thrombolysis in MI grades, left ventricular ejection fraction and left ventricular diastolic function were greater in the coronary group than those in the intravenous group (P<0.05). All patients received follow-up for 30 days and the incidence of bleeding in the coronary group was lower than that in the intravenous group (P<0.05). No significant differences were recorded in the recurrence rates of MI, arrhythmia, myocardial ischemia, thrombocytopenia and mortality between the two groups. In conclusion, the administration of tirofiban into the coronary artery could effectively improve the blood flow, left ventricular function and prognosis of patients with MI treated with PCI. PMID- 26136997 TI - Osteopontin inhibits HIF-2alpha mRNA expression in osteoarthritic chondrocytes. AB - The aim of the present study was to investigate the in vitro effect of osteopontin (OPN) on the expression of hypoxia-inducible factor-2alpha (HIF 2alpha) in chondrocytes and the role of OPN in osteoarthritis (OA). Cartilage was purified from the tibial surfaces of patients with OA of the knee and cultured in vitro to obtain chondrocytes. Recombinant human OPN (rhOPN) and OPN small interfering RNA (siRNA) were used to treat the chondrocytes, and the changes in the expression levels of the HIF-2alpha gene were measured. An anti-CD44 blocking monoclonal antibody (mAb) was used to determine the probable ligand-receptor interactions. Reverse transcription-quantitative polymerase chain reaction assays were designed and validated with SYBR(r) Green dyes for the simultaneous quantification of the mRNA expression levels of OPN and HIF-2alpha. The mRNA expression level of HIF-2alpha was markedly decreased in the rhOPN-treated group compared with that in the control group; by contrast, OPN siRNA increased HIF 2alpha gene expression. CD44 blocking mAb suppressed the inhibitory effect of OPN on HIF-2alpha mRNA expression. The results of the present study suggest that OPN may play a protective role in OA by inhibiting HIF-2alpha gene expression in osteoarthritic chondrocytes through CD44 interaction. PMID- 26136996 TI - XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma susceptibility: A meta-analysis of 11 case-control studies in an Asian population. AB - This meta-analysis was performed to evaluate the association between xeroderma pigmentosum complementary group D (XPD) Lys751Gln and Asp312Asn polymorphisms and susceptibility to hepatocellular carcinoma (HCC). PubMed, Embase, Google Scholar and the Chinese National Knowledge Infrastructure and the Chinese Biomedicine databases were systematically searched to identify relevant studies published up to June 1, 2014. Statistical analyses were performed using Stata version 12.0 software. A total of 11 case-control studies, comprising 2,852 cases and 2,936 controls, were included. The results of the meta-analysis revealed that a significant association between the risk of HCC and variant genotypes of the XPD Lys751Gln and Asp312Asn polymorphisms was evident in the homozygote comparison [Gln/Gln versus Lys/Lys: Odds ratio (OR), 1.831; 95% confidence interval (CI), 1.001-3.349], heterozygote comparison (Lys/Gln versus Lys/Lys: OR, 1.486; 95% CI, 1.044-2.114), dominant model (Gln/Gln + Lys/Gln versus Lys/Lys: OR, 1.540; 95% CI, 1.054-2.249) and allelic contrast (Gln-allele versus Lys-allele: OR, 1.453; 95% CI, 1.032-2.046) for the Lys751Gln polymorphism and the homozygote comparison for the Asp312Asn polymorphism (Asn/Asn versus Asp/Asp: OR, 1.352; 95% CI, 1.010 1.808). By contrast, no significant association was observed in the recessive model for the Lys751Gln polymorphism (Gln/Gln versus Lys/Gln + Lys/Lys: OR, 1.603; 95% CI, 0.924-2.779), or for the heterozygote comparison (Asn/Asp versus Asp/Asp: OR, 1.229; 95% CI, 0.857-1.762), dominant model (Asn/Asn + Asp/Asn versus Asp/Asp: OR, 1.249; 95% CI, 0.910-1.715), recessive model (Asn/Asn versus Asp/Asn + Asp/Asp: OR, 1.250; 95% CI, 0.940-1.663) or allelic contrast (Asn allele versus Asp-allele: OR, 1.226; 95% CI, 0.965-1.557) for the Asp312Asn polymorphism. The present meta-analysis has indicated that the XPD Lys751Gln polymorphism could be a potential biomarker of HCC susceptibility and that the XPD Lys751Gln and Asp312Asn polymorphisms could be risk factors for HCC susceptibility in an Asian population; however, further large-scale and well designed studies are required to reach a more precise and comprehensive conclusion. PMID- 26136998 TI - Association between parental myopia and the risk of myopia in a child. AB - The association between parental myopia and a child's risk of developing the condition is not well understood. Therefore, the present study conducted a meta analysis of the results of observational studies in order to investigate the association between myopia in parents and their child's risk of developing the condition. The current study systematically examined the databases MEDLINE, Embase and Ovid for relevant studies. Two reviewers independently evaluated the data and extracted the odds ratios (ORs) and 95% confidence intervals (CIs) from the suitable studies. Heterogeneity, publication bias and subgroup analyses were performed. The present meta-analysis included 31,677 participants from 16 studies with 8,393 cases of myopia (six prospective cohort, eight cross-sectional and two case-control studies). The OR of giving birth to a child with myopia, according to the prospective cohort, cross-sectional and case-control studies, was 1.53 (95% CI, 1.21-1.85), 1.96 (95% CI, 1.53-2.39), and 2.13 (95% CI, 1.79-2.46), respectively, when one parent had myopia, and 2.10 (95% CI, 1.42-2.77), 2.96 (95% CI, 2.21-3.71), and 2.13 (95% CI, 1.79-2.46), respectively, when two parents had myopia. The current study identified a significant positive association between parental myopia and a child's risk of developing myopia. Children of two parents with myopia had a higher risk of developing myopia compared to those with one myopic parent. PMID- 26136999 TI - Androgen receptor in hepatocarcinogenesis: Recent developments and perspectives. AB - Previous studies have indicated that males are at a higher risk of developing hepatocellular carcinoma (HCC) compared with females. Identifying the factors that cause this gender-specific difference in the incidence of HCC has long been considered important for revealing the molecular mechanisms involved in hepatocarcinogenesis. Given the unprecedented tools that are now available for molecular research, genetic studies have established that the androgen receptor (AR) may be partly responsible for gender disparity in HCC. AR has a dual role, promoting HCC initiation and development, as well as suppressing HCC metastasis. The present review provides an overview of the involvement of AR signaling in HCC. The review highlighted important studies, examples of the direct AR transcriptional target genes involved in HCC and novel theories concerning the conventional concept, suggesting that targeting the AR, rather than the androgen, may provide an improved therapeutic approach for the treatment of HCC. PMID- 26137000 TI - Overexpression of MACC1 and the association with hepatocyte growth factor/c-Met in epithelial ovarian cancer. AB - Metastasis-associated in colon cancer-1 (MACC1) is a gene that has been newly identified by a genome-wide search for differentially expressed genes in human colon cancer tissues, metastases and normal tissues. MACC1 exerts an important role in colon cancer metastasis through upregulation of the c-Met proto-oncogene. The tyrosine kinase receptor encoded by the c-Met oncogene exhibits the unusual property of mediating the invasive growth of epithelial cells upon binding with the hepatocyte growth factor (HGF). MACC1 has been investigated with regard to colon carcinoma and MACC1 expression is associated with metastasis in various types of human cancer. However, the value of MACC1 as a potential biomarker for ovarian cancer remains unknown, although the c-Met/HGF receptor has been shown to be overexpressed in epithelial ovarian cancer tissues. To investigate the role of MACC1 in epithelial ovarian tumors, the expression levels of MACC1 mRNA in ovarian tumor specimens were analyzed together with the prognostic significance. MACC1 protein expression was also detected in the epithelial ovarian tissue specimens, and the effects of MACC1 overexpression on ovarian cancer migration, invasion and prognosis were evaluated. Due to the close association between MACC1 and c-Met expression levels in colon cancer, the expression levels of HGF/c-Met in the ovarian specimens were also examined to determine whether such a correlation is also present in epithelial ovarian cancer. A total of 92 epithelial ovarian tissue samples were used to assess the expression levels of MACC1 mRNA and protein using reverse transcription-polymerase chain reaction and immunohistochemical methods, respectively. The serum levels of MACC1 protein expression in patients with epithelial ovarian cancer were detected by enzyme linked immunosorbent assay. The results indicated that MACC1 may be important in the malignant progression of epithelial ovarian tumors, in particular for early stage patients. Thus, MACC1 may become a predictor of prognosis and a therapeutic target in the treatment of ovarian tumors. The combined detection of MACC1 and HGF/c-Met is therefore important in assessing the prognosis of patients with malignant epithelial ovarian tumors. PMID- 26137001 TI - Effects and mechanisms of blocking the hedgehog signaling pathway in human gastric cancer cells. AB - Excessive activation of the hedgehog (Hh) signaling pathway is important in a variety of human cancer cell types, including gastric cancer. However, the underlying mechanisms of the Hh signaling pathway in inducing gastric tumorigenesis and its downstream target genes are largely unknown. In the present study, the inhibitory effect of cyclopamine on the Hh signaling pathway was investigated in the human gastric cancer AGS cell line. It was identified that cyclopamine treatment inhibited the proliferation, migration and invasion of the AGS cells in a dose- and time-dependent manner, and resulted in the downregulation of a number of key Hh signaling pathway-associated factors [glioma associated oncogene homolog 1, C-X-C chemokine receptor type 4 and transforming growth factor (TGF)-beta1] at the RNA and protein levels. Furthermore, the secretion of TGF-beta1 was significantly reduced following the administration of cyclopamine to the AGS cells. The results of the present study provided insight into the mechanisms by which the Hh signaling pathway regulates gastric cancer formation and identified the Hh signaling pathway as a potential novel therapeutic target in human gastric cancer. PMID- 26137002 TI - Neurokinin-2 receptor polymorphism predicts lymph node metastasis in colorectal cancer patients. AB - To analyze the single nucleotide polymorphisms (SNPs) of two subtypes of neurokinin (NK) receptors, NK1R and NK2R (also known as TAC1R and TAC2R), in colorectal cancer (CRC), peripheral blood samples were collected from 199 CRC patients. Direct-sequencing was performed to identify the NK1R rs10198644 and NK2R rs4644560 SNPs. Genotype results were correlated with clinical factors. The allele frequencies of NK1R rs10198644 GC, CC and GG were 52, 17 and 31%, respectively, while that of NK2R rs4644560 GC, CC, and GG were 36, 50 and 14%, respectively. Patients with NK2R rs4644560 GC exhibited more positive lymph nodes than those with CC (mean, 2.2 vs. 1.3; P=0.016). Further analysis highlighted that the number of positive lymph nodes was also increased in the NK2R rs4644560 GC/NK1R rs10198644 GG group compared with the NK2R rs4644560 GG/NK1R rs10198644 GG group (mean, 2.2 vs. 0.9; P=0.04). These data suggested that the NK2R rs4644560 GC polymorphism alone or combination with NK1R rs10198644 GG may be a promising prognostic marker of lymph node metastasis in CRC patients. PMID- 26137003 TI - Effect of combined 5-aza-2'deoxycytidine and cisplatin treatment on the P15 lung adenocarcinoma cell line. AB - Aberrant promoter hypermethylation resulting in the epigenetic silencing of apoptosis-associated genes is a key process in the chemotherapeutic treatment of cancer. The nucleoside analog, 5-aza-2'deoxycytidine (DAC), inhibits the activity of DNA methyltransferase enzymes and is able to restore the expression levels of genes that have been silenced by aberrant DNA methylation. The aim of the present study was to investigate the effect of combined treatment with DAC and cisplatin (CDDP) on the lung adenocarcinoma cell line, P15. Growth inhibition was examined using a clone formation assay and growth inhibitory activities by cell counting during treatment with DAC alone, CDDP alone or DAC followed by CDDP. In addition, changes in the mRNA expression levels of various apoptosis-associated genes following treatment with increasing concentrations of DAC were determined using reverse transcription-polymerase chain reaction. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis was used to detect the number of apoptotic P15 tumor cells following treatment with DAC and/or CDDP. The results indicated that DAC treatment alone restored the mRNA expression levels of p73, p16INK4a , B-cell lymphoma (Bcl)-2-associated agonist of cell death and Bcl-2-associated X protein. In addition, combined therapy with DAC and CDDP was found to significantly suppress the growth of P15 tumor cells compared with DAC or CDDP treatment alone. In conclusion, DAC may enhance the chemosensitivity of the P15 cell line to treatment with CDDP. PMID- 26137004 TI - Malignant conversion of a solitary squamous cell papilloma in the trachea treated by radiotherapy: A case report. AB - The present study described a rare case of malignant conversion of a solitary papilloma in the trachea, in addition to reviewing the current literature. A 54 year-old male presented with a cough, sputum and dyspnea. Chest computed tomography revealed a mediastinal soft-tissue mass in the trachea. A tumor biopsy, performed using a flexible bronchofiberscope, identified a squamous cell papilloma with moderate to severe atypical hyperplasia, as well as the formation of squamous cell carcinoma. Polymerase chain reaction analysis did not detect presence of human papilloma virus in the tumor. The patient was subsequently treated with radiotherapy and no evidence of recurrence was observed during a two year follow-up period. To the best of our knowledge, this is the first study to describe the malignant conversion of a solitary papilloma in the trachea, which was subsequently treated with radiotherapy. PMID- 26137005 TI - Primary pure carcinoid tumors of the testis: Clinicopathological and immunophenotypical characteristics of 11 cases. AB - Primary pure carcinoid tumors of the testis (pPCTT) are rare, and there are only a limited number of studies available. In the present study we described the clinicopathological and immunophenotypical characteristics of 11 cases from our institution between 1978 and 2014, and reported our experiences of the diagnosis and treatment of these patients. The patients ranged in age from 26 to 68 years old, with a median age of 48 years. One patient (9%) was classified as pT2 and 10 (91%) were pT1. Histologically, 7 cases were diagnosed as classical carcinoid tumors, while the other 4 cases were identified as atypical carcinoid tumors. The most common growth pattern was a mixed insular, acinar, rosetted, solid and trabecular pattern. Immunohistochemical staining revealed positive expression of neuron-specific enolase in all cases, and CgA, Syn and CD56 markers in 8 (72.7%), 10 (90.9%) and 9 cases (81.7%), respectively. In addition to radical orchiectomy, 9 patients (81.7%) received a combined modality of treatment. Follow-up data were available for 8 patients. Seven were alive at the last follow-up without recurrence, and one patient succumbed to cerebral hemorrhage 7 years after surgery. In summary, localized pPCTT is a rare disease with an indolent clinical course. When a testicular carcinoid tumor is identified, a metastasis or an intestinal primary tumor should be excluded, particularly when the testicular tumor is large. A tumor size <=6.0 cm and the histological appearance had little relation with metastatic behavior. PMID- 26137006 TI - Endostatin improves cancer-associated systemic syndrome in a lung cancer model. AB - Cancer-associated systemic syndrome (CASS) is characterized by a constellation of symptoms, including progressive weight loss, anemia, endocrine disorders, gastrointestinal dysfunction, muscle and adipose atrophy, hepatic peliosis and kidney failure. The present study assesses the effects of endostatin on CASS and any possible underlying mechanism in tumor-bearing mice. The results showed that the inoculation of Lewis lung carcinoma cells into mice led to CASS that was characterized by a notable decrease in body weight, severe anemia phenotype, disordered biochemistry, hepatosplenomegaly, and a marked increase in serum vascular endothelial growth factor (VEGF), tumor necrosis factor alpha and interleukin-6 (IL-6). The continuous injection of 10 mg/kg/day endostatin suppressed tumor growth and alleviated CASS in the tumor-bearing mice, as shown by weight gain, improvement in biochemistry and anemia, and the preservation of organ function. The effects of endostatin on CASS in the tumor-bearing mice were accompanied by the downregulation of serum VEGF and IL-6. Collectively, these findings indicate that endostatin improves CASS in tumor-bearing mice by decreasing the serum levels of VEGF and IL-6. PMID- 26137007 TI - Role of the CacyBP/SIP protein in gastric cancer. AB - Various reports indicate that calcyclin binding protein/Siah-1-interacting protein (CacyBP/SIP) is an important protein in tumorigenesis, but whether CacyBP/SIP promotes or suppresses cancer may depend on the cell type. In order to investigate whether CacyBP/SIP is significant in gastric cancerous tumorigenesis, the present study used immunohistochemistry to analyze 181 gastric cancer tissue samples, as well as 181 healthy tissue samples from the same gastric cancer patients. The immunohistochemical results were compared against patient data and pathological analysis of the tissue slices, including gender, age, degree of tumor differentiation and tumor, node, metastasis (TNM) stage. In addition, the level of CacyBP/SIP expression was detected in three frozen tissue samples of gastric adenocarcinoma using western blot analysis. Of the 181 cases analyzed in the present study, 80 cases were identified as non-metastatic gastric cancer and 101 cases were identified as gastric cancer that had metastasized to the lymph nodes. Tissue biopsies from the two sets of patients were examined using immunohistochemistry to identify the level of CacyBP/SIP expression in metastatic and primary gastric cancer tissues. Statistical analyses were performed on all data. The immunohistochemical analysis revealed that CacyBP/SIP was expressed in 31% (56/181) of gastric adenocarcinoma tissue samples and 7% (12/181) of adjacent non-cancerous gastric tissues (P<0.05). Furthermore, the expression levels of CacyBP/SIP were higher in cancerous tissue compared with the adjacent non cancerous gastric tissue using western blotting. No association was identified between CacyBP/SIP expression and patient age (P=0.975), gender (P=0.185), degree of tumor differentiation (P=0.076) or TNM stage (P=0.979). Among the 101 patients with metastatic gastric cancer, CacyBP/SIP was expressed at primary sites in 31% (31/101) of cases and at metastatic sites in 26% (26/101) of cases (P=0.434). However, among the 80 patients with non-metastatic gastric cancer, CacyBP/SIP was expressed at the tumor site in 34% (27/80) of cases, which was not significantly different from the 31% (25/80) of cases in the metastatic group (P=0.662). These findings indicate that CacyBP/SIP expression is not a marker of gastric cancer or metastatic gastric cancer, nor does it appear to correlate with the clinicopathological features of gastric cancer. PMID- 26137008 TI - Primary malignant melanoma of the esophagus: A case report and review of the literature. AB - Primary malignant melanoma of the esophagus (PMME) is a rare malignancy and the prognosis is typically poor. There is currently a lack of appropriate treatment strategies and clear guidance. The current study presents the case of a 65-year old female with a two-month history of progressive dysphagia, the investigations of which resulted in a diagnosis of PMME. The patient was treated with a radical transhiatal esophagectomy with subcarinal lymphadenectomy followed by combined chemoimmunotherapy. The patient remains alive with no evidence of tumor progression at the 12-month follow-up. The purpose of the present study was to report a new case and to review the recent relevant literature regarding the treatment of PMME. PMID- 26137009 TI - Gastrointestinal bleeding due to pancreatic metastasis of non-small cell lung cancer: A report of two cases and a literature review. AB - The current study presents two cases of gastrointestinal (GI) bleeding due to pancreatic metastasis of non-small cell lung cancer (NSCLC). The two patients had a history of lung adenocarcinoma prior to pancreatic metastasis. The first patient presented with melena, epigastric pain and weight loss, and the second patient presented with melena and weight loss. The diagnoses were confirmed by biopsy of the metastatic lesions. Immunohistochemistry is useful for managing the differential diagnosis between lung cancer and pancreatic carcinoma in patients with a history of lung cancer. Chemotherapy prolonged the survival of the second patient. However, the first patient received no chemotherapy and succumbed to NSCLC six weeks after the diagnosis of metastatic pancreatic cancer. GI bleeding as a result of pancreatic metastasis of NSCLC is extremely rare; including the present two cases, only three cases have been reported in the English literature. The current study is presented in order to increase the awareness of GI hemorrhage as a manifestation of this relatively rare condition. PMID- 26137011 TI - Struma ovarii accompanied by mature cystic teratoma of the other ovary: A case report and literature review. AB - Struma ovarii, as a monodermal variant of ovarian teratoma, constitutes <3% of ovarian teratomas. It is difficult determine a diagnosis prior to surgery. The current study reports an unusual case of struma ovarii occurring in a 49 year-old female, which was accompanied by mature cystic teratoma involving the other ovary. The final pathological diagnosis was confirmed as struma ovarii based on the typical morphology of the thyroid follicles and the results of immunohistochemical staining. The bilateral tumors were resected and follow-up examinations were planned at four month intervals. At the time of writing, the patient was well and no tumor recurrence had been identified. PMID- 26137010 TI - Detection of pleural plaques in workers exposed to inhalation of natural fluoro edenite fibres. AB - Fluoro-edenite is a natural mineral species initially isolated in Biancavilla, Sicily. The fibres are similar in size and morphology to certain amphibolic asbestos fibres, the inhalation of which may cause chronic inflammation and cancer. Occupational asbestos exposure is known to be associated with pleural and lung diseases, including pleural plaques. The aim of this study was to report the pleural and lung parenchymal lesions detected by high-resolution computed tomography (HRCT) in a group of construction workers exposed to fluoro-edenite. Information regarding life habits and occupational history was collected from 43 workers enrolled into the study. The participants underwent physical examination, blood analysis, search for uncoated fibres and ferruginous bodies in the sputum, pulmonary function tests, including diffusion capacity for carbon monoxide (TLCO), and HRCT chest imaging. A general descriptive outcome analysis was also conducted; a prevalence ratio (PR) with 95% confidence interval and a two-tailed test P-value were calculated for pleural plaques using log-binomial regression, measuring plaque size and thickness, and cumulative exposure index (CEI). The mean values of the functional respiratory tests were within the normal range for all participants. A restrictive ventilatory defect was identified in two (5%) subjects and an obstructive ventilatory defect in three (7%) subjects. TLCO was reduced in two additional participants. Fibres were detected in 19 (44%) of subjects. Pleural involvement was documented in 39 (91%) workers, of whom 31 (72%) had bilateral plaques. Calcifications were detected in 25 (58%) of these participants. PR indicated a progressive increase in the risk of developing pleural lesions with rising CEI, i.e. length of exposure. The present findings demonstrate for the first time the presence of pleural plaques in the lungs of subjects exposed to fluoro-edenite fibres, and not to asbestos, through residing in Biancavilla and through their occupation. PMID- 26137012 TI - Enhancement of oxaliplatin-induced cell apoptosis and tumor suppression by 3 methyladenine in colon cancer. AB - Oxaliplatin (OX) has been widely used in adjuvant and palliative treatments of advanced colon cancer; however, cancer cells ultimately become resistant in the majority of cases. Therefore, the development of a novel strategy to overcome this resistance is important for the effective treatment of colon cancer. Cell autophagy reduces the sensitivity of cancer cells to therapeutic reagents in various types of human cancer; therefore, the present study used murine CT26 colon carcinoma cells to explore whether inhibition of autophagy by 3 methyladenine (3-MA) is able to enhance OX-induced apoptosis in vitro and OX suppressed tumor growth in vivo. CT26 cells were treated with 3-MA, OX, or 3-MA plus OX, and the autophagy, apoptosis and proliferation of the CT26 cells was investigated. Additionally, the therapeutic efficiency of the combination of 3-MA and OX treatment was evaluated in vivo by determining the survival time of the tumor-bearing mice and, thus, tumor growth rate. The treatment of CT26 cells in vitro with OX alone increased autophagy as well as apoptosis, whereas treatment with 3-MA plus OX markedly inhibited OX-induced autophagy, but increased OX induced cell apoptosis. Furthermore, the combination of OX and 3-MA treatment significantly suppressed tumor growth in vivo and prolonged mouse survival time when compared with OX treatment alone. Similarly, 3-MA increased OX-induced cell apoptosis and decreased autophagy in xenograft tumor tissues. Thus, the administration of 3-MA may increase tumor cell sensitivity to OX by reducing its autophagic effects and enhancing its apoptotic effects. Data obtained in the present study indicates that the clinical combination of an autophagy inhibitor with OX may increase the therapeutic effect of OX and improve the clinical outcome of patients with colon cancer. PMID- 26137013 TI - Somatic mutations in glioblastoma are associated with methylguanine-DNA methyltransferase methylation. AB - The high level of methylguanine-DNA methyltransferase (MGMT) in glioblastoma is responsible for resistance to alkylating agents, such as temozolomide (TMZ). In glioblastomas with a methylated MGMT promoter, MGMT deficiency is presumed, resulting in an enhanced effect of TMZ. The aim of the present study was to investigate whether genomic alterations work synergistically with MGMT methylation status and contribute to the response to treatment and overall prognosis in glioblastoma. The current study included a cohort of 35 glioblastoma patients, with MGMT promoter methylation present in 48% of tumors. MGMT methylation was associated with significantly longer median survival (29.0 months) compared with patients without MGMT methylated tumors (12.0 months), as well as longer median time to progression following TMZ treatment (13.2 months, compared with 5.6 months for patients with an unmethylated MGMT status). In addition, somatic variants in hot spot exonic regions of 50 key cancer genes were examined in these glioblastomas. Non-synonymous mutations in methylated MGMT glioblastomas were four times higher compared with unmethylated MGMT glioblastomas. Furthermore, significantly increased frequencies of mutations in the TP53, CDKN2A, PTEN and PIK3CA genes were detected in MGMT methylated glioblastomas. The relative significance of these mutations, and their contribution to TMZ sensitivity, adjunct to MGMT methylation, require further investigation in a larger cohort. PMID- 26137014 TI - Mixed large cell neuroendocrine carcinoma and mucosa-associated lymphoid tissue lymphoma of the lung: A case report. AB - In the present study, a 79-year-old male was referred to Kobe City Medical Center General Hospital due to an abnormal shadow that was revealed on a chest X-ray. The patient possessed a five-year history of consolidation in the right lower lobe, which was diagnosed as chronic aspiration pneumonia and followed up. However, the abnormal shadow adjacent to the pleura gradually increased in size and a novel mass appeared in the right lower lobe that rapidly increased in size. A repeat biopsy revealed a combination of large cell neuroendocrine carcinoma with a clinical tumor-node-metastasis (cTNM) stage of cT2bN2M0 (stage 3A) and mucosa-associated lymphoid tissue lymphoma at Ann Arbor stage 1E. Chemoradiotherapy markedly affected the lesion and the size of the mass was significantly reduced subsequent to four cycles of chemotherapy, which was considered to be a near complete response. The present study reports an extremely rare combination of tumors. The disease course was followed over a period of six years, which included the onset of disease, and the present case may therefore be valuable in clarifying the mechanism of lung cancer development. PMID- 26137015 TI - Adenoma detection rate in 41,010 patients from Southwest China. AB - Adenoma detection rate (ADR) is considered as an important predictor of the risk of interval colorectal cancer following a screening colonoscopy. A retrospective review of all the patients who underwent colonoscopy in the First Affiliated Hospital of Guangxi Medical University (Nanning, China) between 2003 and 2012 was performed, with the aim of estimating the ADR in Southwest China and determine the effects of age, gender and polyp location on ADR. Demographic information and data regarding the timing of the colonoscopy, number of polyps removed, polyp location and pathological types of polyps were collected and analyzed. The patients were grouped according to colonoscopy date, polyp location, gender and age. The chi2 test was used to compare the ADR between the different age and gender groups and the Cochran-Armitage trend test was used to calculate the statistical significance of the ADR trend across age groups. A two-tailed value of P<0.05 was considered to indicate statistically significant differences. A total of 41,010 patients were included, of whom 7,219 were diagnosed with at least one adenoma on pathological examination. Therefore, the ADR value of the 41,010 patients screened in the present study was 17.6%. There was a statistically significant trend of increasing ADR with increasing age in both genders (P<0.05). In addition, the ADR of male patients was significantly higher compared with that of female patients in all age groups (all P<0.05). The ADR of patients aged >50 years was significantly higher compared with that of patients aged <50 years (28.8 vs. 11.0%, respectively; P<0.05). In addition, 20% of the cases of detected adenomas occurred in the rectum, 47% in the left colon and 33% in the right colon. PMID- 26137016 TI - Olfactory ensheathing cell tumor: A case report and review of the literature. AB - Olfactory ensheathing cell tumors (OECTs) are rare malignancies that occur in the anterior fossa. Little is known with regard to their clinical, radiological and immunohistochemical characteristics. The current study reports the case of a 20 year-old male with an OECT, who presented with a severe headache and a generalized convulsion. Cranial magnetic resonance imaging revealed heterogeneous enhancement of the tumor in the left anterior fossa. Complete removal of the tumor via a left frontal craniotomy was conducted, which relieved the patient's headache; however, this resulted in left-sided anosmia that remained during the two-month follow-up. The tumor was immunopositive for vimentin and S-100, and immunonegative for epithelial membrane antigen and Leu-7. The clinical data, imaging features, intraoperative findings and immunohistochemical characteristics of an additional seven cases reported in the literature are also reviewed and analyzed, providing important clinical information for the pre-operative diagnosis and intraoperative removal of OECTs. PMID- 26137017 TI - Expression of CC chemokine receptor 5 in clear cell renal cell carcinoma and its clinical significance. AB - DNA hypomethylation was the initial epigenetic abnormality recognized in human malignancy. In the present study, the GoldenGate high-throughput genotyping assay was adapted to determine the methylation state of 1,505 specific CpG sites in 807 cancer-related genes. The methylation results revealed that CC chemokine receptor 5 (CCR5) was hypomethylated (mean beta-value difference, -0.21) in clear cell renal cell carcinoma (CCRCC) tissue. Tissue samples from 61 CCRCC cases were used for immunohistochemical staining, and patients with low CCR5 expression (n=44) were compared with those with high CCR5 expression (n=17). Tumor (T) stage was significantly lower in the low expression group compared with the high expression group (P=0.047). The Fuhrman grade of patients in the low expression group was significantly lower than that of patients in the high expression group (P=0.044). Whilst the node (N) and metastasis (M) stages of the CCR5 low expression group appeared to be lower compared with those of the CCR5 high expression group; this difference was not statistically significant (N stage, P=0.632; M stage, P=0.896). Additionally, patients in the low expression group had lower risks of postoperative tumor recurrence (P=0.110) and mortality from CCRCC (P=0.159) compared with those in the high expression group, however, this was also without statistical significance. The results indicate that CCR5 hypomethylation is associated with cancer tissue to a greater extent than normal tissue. Although the biological function of CCR5 in CCRCC remains to be established, low CCR5 expression is associated with low T stage and low Fuhrman grade in these patients. PMID- 26137018 TI - Expression and prognostic significance of TAp73 and DeltaNp73 in FIGO stage I-II cervical squamous cell carcinoma. AB - The purpose of the present study was to investigate the expression of TAp73 and DeltaNp73 in cervical squamous cancer cells, and to evaluate the prognostic significance of TAp73 and DeltaNp73 expression in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical squamous cell carcinoma (SCC). The immunohistochemical expression of TAp73 and DeltaNp73 was evaluated in 59 FIGO stage I-II cervical SCC tumor samples. Correlations with clinicopathological characteristics were determined by chi2 test. The prognostic impact of TAp73 and DeltaNp73 expression with regard to overall survival (OS) was determined by the Kaplan-Meier method. High TAp73 and DeltaNp73 expression was detected in 79.7% (47/59) and 76.3% (45/59) of patients, respectively. The expression of TAp73 and DeltaNp73 was not associated with age, FIGO stage, pathological differentiation or lymph node metastasis. The 3-year OS rates associated with low and high TAp73 expression were 75.0 and 83.0%, respectively (chi2=0.33; P=0.568), whereas those associated with low and high DeltaNp73 expression were 100.0 and 75.6%, respectively (chi2=3.90; P=0.048). High expression levels of TAp73 and DeltaNp73 were frequently observed in the cervical squamous cancer cells. Overall, high expression levels of DeltaNp73 may indicate an unfavorable prognosis in patients with early-stage cervical SCC. PMID- 26137019 TI - Functional reconstruction of the knee extension mechanism following wide resection for a prepatellar soft-tissue sarcoma: A case report. AB - Functional reconstruction following a wide resection for a malignant musculoskeletal tumor is often challenging, particularly for juxta-articular tumors. The current study describes a novel surgical procedure for the functional reconstruction of the knee extensor mechanism with a pedicle frozen auto-bone and -tendon graft, in a case of prepatellar clear cell sarcoma. The active range of motion of the knee was from 0-135 degrees , and the extension muscular strength of the knee was evaluated as 5/5 by a manual muscle test at 14 months post surgery (International Society of Limb Salvage score, 73%); this was improved compared with a similar procedure previously described by Muramatsu et al. This procedure must be considered following the wide resection of juxta-articular malignant musculoskeletal tumors. PMID- 26137020 TI - Immunostaining for thyroid transcription factor 1, Napsin A, p40, and cytokeratin 5 aids in differential diagnosis of non-small cell lung carcinoma. AB - The present study aimed to examine the effectiveness of immunostaining of cytological specimens in discerning squamous from non-squamous cell carcinoma. Various combinations of six antibodies were examined in order to determine the optimal combination for use in differential diagnosis. Immunostaining was performed using tumor imprint smears obtained from 70 lung carcinoma cases. The results were scored based on positive area and intensity. For objective evaluation, scores for thyroid transcription factor 1 (TTF-1), napsin A, and CK CAM5.2 were expressed with positive values, while those for p40, cytokeratin (CK) 5/6 and CK5 were expressed with negative values. Histograms were produced to evaluate which combination was the most effective in differentiating squamous cell carcinoma from adenocarcinoma. The sensitivity for these molecules in adenocarcinoma was 88% for TTF-1, 85% for napsin A, and 100% for CAM5.2. In squamous cell carcinomas, sensitivity was determined to be 90% for p40, 86% for CK5, and 76% for CK5/6. The specificity for these molecules was calculated as 100%, 95%, 43%, 98%, 100% and 95%, respectively. Each combination was evaluated for scoring and the values were averaged. The most effective combination for mode and mean was TTF-1, napsin A, p40, and CK5, for which all adenocarcinomas had a score >1, and all squamous cell carcinomas scored <-2. Immunostaining scoring may therefore be useful for the differential diagnosis of these carcinomas when a limited number of tumor cells are present. PMID- 26137021 TI - Long-term use of a once-a-day fentanyl citrate transdermal patch in lung cancer patients. AB - Transdermal fentanyl is widely administered as an analgesic therapy for cancer patients. Recently, a novel fentanyl citrate transdermal patch was developed in Japan, which is the first such patch that requires changing only once a day. The patch releases more stable serum fentanyl concentrations and results in less frequent adverse skin symptoms compared with the conventional 72-h transdermal fentanyl patch. A previous study has reported the short-term analgesic effects and safety of this transdermal patch. However, the long-term efficacy has yet to be determined. Therefore, the present study retrospectively investigated the adverse effects and outcomes of treatment with this product in 46 lung cancer patients. In total, 35 (76%) patients were able to continue the treatment until the end of the observation period, including 32 (69%) who succumbed to the disease and three (7%) who were transferred from Nagoya City University Hospital to a hospice. Of the 11 (24%) discontinued cases, six were changed to a course of injectable opioids for the palliation of terminal symptoms, including dyspnea. Adverse effects were observed in 11 (24%) cases, but discontinuation due to adverse effects occurred in only four cases. Therefore, the present study indicates that palliative treatment with the once-a-day fentanyl citrate transdermal patch is well-tolerated by lung cancer patients. PMID- 26137022 TI - Primary non-gestational pure choriocarcinoma arising in the ovary: A case report and literature review. AB - Pure non-gestational choriocarcinoma is a primary germ cell neoplasm that has been defined as a tumor without other germ cell elements. The current study presents an extremely rare case of non-gestational pure choriocarcinoma in a postmenarcheal young female and describes details of the tumor, including the clinicopathological findings. The patient was a 10-year-old female who underwent salpingo-oophorectomy. Histologically, the extensive hemorrhagic tumor was composed of choriocarcinoma without additional germ cell tumor components. The tumor cells were immunohistochemically positive for epithelial markers, including cytokeratins and epithelial membrane antigens, and there was a positive cytoplasmic reaction for beta-human chorionic gonadotropin in the syncytiotrophoblasts. Furthermore, numerous tumor cells were immunohistochemically positive for the beta2-microglobulin antibody. The patient received adjuvant cisplatin, etoposide and bleomycin chemotherapy, and is currently disease-free without evidence of recurrence or metastasis subsequent to 62 months of follow-up. PMID- 26137023 TI - In vivo18F-fluorodeoxyglucose-positron emission tomography/computed tomography imaging of pancreatic tumors in a transgenic rat model carrying the human KRASG12V oncogene. AB - A novel KRAS-mediated transgenic rat model has previously been demonstrated, in which animals develop multiple pancreatic ductal adenocarcinoma (PDAC) that is histologically similar to human PDAC within two weeks. Positron emission tomography (PET)/computed tomography (CT) is commonly used for the diagnosis and staging of PDAC in humans, and can be adopted for optimal use in animal experiments. The aim of the present study was to evaluate the carcinogenic process in a rat pancreatic carcinoma model using small-animal multimodality imaging systems. The utility of fluorodeoxyglucose (FDG)-PET/CT in detecting the location and size of PDAC during tumor development in the present transgenic rat model was assessed. A small animal multimodality PET/CT system and contrast enhanced CT (CECT) system were used for the imaging analysis of KRASG12V male transgenic rats (n=6), which developed pancreatic tumors following the administration of an injection of Cre recombinase (Cre)-carrying adenovirus. Laparotomies performed at six weeks post-treatment revealed that all three (100%) Cre-expressing rats developed pancreatic tumors that were <2 mm in diameter, none of which were detected by 18F-FDG PET/CT or CECT. At eight weeks post-treatment, the pancreatic tumors were heterogeneously visualized by 18F-FDG-PET/CT and CECT in two of the three rats. Furthermore, the autopsies confirmed that all three rats had developed pancreatic tumors. These novel findings provide evidence that the FDG-PET/CT imaging system is a valuable tool for the evaluation of the carcinogenic process, and one which may aid in treatment and preventive methods for pancreatic tumors in mammalian models. A limitation associated with the early detection of PDACs warrants further investigation. PMID- 26137024 TI - Reduced administration of rasburicase for tumor lysis syndrome: A single institution experience. AB - In the present study, the dosage and duration of rasburicase administration were retrospectively evaluated for the ability to control the serum uric acid (S-UA) level in 13 patients diagnosed with hematological malignancies and tumor lysis syndrome (TLS), or those at risk of developing TLS, at the University of Fukui Hospital. At the time of diagnosis, seven patients already exhibited laboratory TLS, and three demonstrated clinical TLS. All patients received rasburicase in addition to chemotherapy agents. The median dose was 0.19 mg/kg (range, 0.13-0.25 mg/kg), and the median duration was four days (range, 1-7 days). Six patients sequentially received a xanthine oxidase inhibitor, allopurinol or febuxostat. The primary estimate was the normalization of the S-UA level at the end of rasburicase treatment and on treatment day seven. The average S-UA level prior to treatment was 10.4+/-4.5 mg/dl (mean +/-standard deviation), and 11 out of 13 patients demonstrated a S-UA level >7 mg/dl. The S-UA level at the end of rasburicase administration was 0.5+/-1.5 mg/dl and the S-UA level at day seven was 1.4+/-1.5 mg/dl. All the patients achieved normalization of the S-UA level. On day seven subsequent to the initiation of treatment, the patients receiving rasburicase for a maximum of three days exhibited an S-UA level of 1.9+/-1.8 mg/dl, while the patients receiving rasburicase for longer than three days demonstrated an S-UA level of 1.0+/-1.3 mg/dl (P=0.20; Mann-Whitney test). The administration of 0.13 mg/kg and 0.22 mg/kg resulted in comparable UA level reductions. The administration of allopurinol or febuxostat following rasburicase administration suppressed the re-increase in S-UA level. Therefore, it was concluded that reduced administration of rasburicase successfully controlled the S-UA level in TLS. PMID- 26137025 TI - Hepatoid adenocarcinoma of the stomach: A case report and review of the literature. AB - Hepatoid adenocarcinoma is a rare tumor, associated with an extremely poor prognosis. In the present report, a 72-year-old female presented to Huashan Hospital (Shanghai, China) with upper abdominal discomfort and, following endoscopy, an ulcerated lesion was observed in the stomach. A computed tomography scan revealed a mass in the antrum of the stomach and the alpha-fetoprotein level was normal. Sections of the mass exhibited malignant cells arranged in a solid to trabecular pattern; the cells were polygonal shaped with well-defined cytoplasmic borders. Immunohistochemical analysis was performed and the cells were positive for Hep1, CK, CK8, CK18 and P53. The histological features together with the immunohistochemical findings were diagnostic of a hepatoid adenocarcinoma of the stomach. Immunohistochemical studies may aid in the identification of the characteristic features and prevent the misdiagnosis of this tumor. PMID- 26137026 TI - Gelsolin regulates proliferation, apoptosis, migration and invasion in human oral carcinoma cells. AB - Gelsolin (GSN) is one of the most abundant actin-binding proteins, and is involved in several pathological processes, including Alzheimer's disease, cardiac injury and cancer. The aim of the present study was to assess the effect of GSN on the growth and motility of oral squamous cell carcinoma Tca8113 cells. The overexpression vector pcDNA3.1-GSN was transfected into Tca8113 cells and the stable GSN overexpression cell line was identified based on G418 antibiotic selection. The effect of GSN overexpression on the proliferation, apoptosis, migration and invasion of Tca8113 cells was examined using a cell counting kit-8 assay, flow cytometry and Transwell assays. The results revealed that GSN overexpression significantly promoted the cell proliferation and apoptosis of Tca8113 cells. In addition, Transwell assays demonstrated that the migration and invasion abilities of Tca8113 cells were enhanced by GSN overexpression. Therefore, the upregulation of GSN promotes cell growth and motility, indicating that it may perform a vital function in the progression of human oral cancers. PMID- 26137027 TI - Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF kappaB signaling. AB - Recently, the nuclear factor (NF)-kappaB inhibitor parthenolide (PT) was identified as a promising anticancer agent for the promotion of cancer cell apoptosis. Additionally, our previous study demonstrated that PT administration suppresses tumor growth in a xenograft model of colorectal cancer cells via regulation of the B-cell lymphoma-2 (Bcl-2) family. However, the role of PT in the development of colitis-associated colon cancer (CAC) is poorly understood. Therefore, the aim of the present study was to investigate the effects of PT administration on CAC using a murine model. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were administered to induce experimental CAC in the following three groups of treated mice: i) AOM and DSS plus vehicle; ii) AOM, DSS and 2 mg/kg PT; and iii) AOM, DSS and 4 mg/kg PT. It was demonstrated that the histological acuteness of AOM/DSS-induced CAC was significantly reduced following the administration of PT, resulting in decreased NF-kappaB p65 expression levels via a blockade of phosphorylation and subsequent degradation of inhibitor of kappaB-alpha (IkappaBalpha). Furthermore, PT administration appeared to enhance the process of carcinogenesis via the downregulation of the antiapoptotic proteins Bcl-2 and Bcl-extra large, mediated by inhibition of NF-kappaB activation. Apoptosis and caspase-3 expression were markedly increased in the PT treated group. These findings indicate that PT inhibits IkappaBalpha phosphorylation and NF-kappaB activation, resulting in the initiation of apoptosis and the eventual suppression of CAC development. The beneficial effects of PT treatment observed in the experimental CAC model indicate the potential chemopreventive and therapeutic role of PT in CAC. PMID- 26137028 TI - Vav3 oncogene is upregulated and a poor prognostic factor in breast cancer patients. AB - The Vav3 oncogene is overexpressed and has a significant role in the tumorigenesis of prostate cancer and glioblastoma. In the present study, the expression status and prognostic value of Vav3 expression was investigated in breast cancer. Vav3 protein levels were analyzed by immunoblotting in human breast cancer and epithelial cell lines. Immunohistochemistry was used to detect Vav3 in a tissue microarray of 173 breast cancers and 19 benign breast lesions. Statistical analysis was performed to reveal the association between Vav3 expression and clinicopathological parameters. Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier analysis and the Cox regression model. The Vav3 protein level was higher in the breast cancer cell lines than in the normal human breast cells. Vav3 was expressed in 86.1% of breast cancer patients, but in only 15.6% patients with benign breast disease. Patients with negative estrogen receptor expression, axillary lymph node involvement and a high tumor-node-metastasis stage demonstrated a higher positive rate of Vav3 expression. The Kaplan-Meier survival analysis revealed that patients with higher Vav3 expression exhibited shorter DFS and OS times. The multivariate Cox analysis revealed that Vav3 was a prognostic factor of survival. Overall, Vav3 was overexpressed in human breast cancer cells and this correlated with a shorter survival time, indicating that Vav3 is a biomarker of a poor prognosis for breast cancer patients. PMID- 26137029 TI - Renal-type clear cell carcinoma of the prostate: A case report. AB - Renal-type clear cell carcinoma of the prostate is a rare and novel tumor that has only been identified in recent years. The present study describes a lesion in the prostate of a 64-year-old male with a two-year history of urinary frequency, urgency and difficulty, who was admitted to the San Ai Tang Hospital for benign prostatic hyperplasia, and subsequently underwent transurethral resection of the prostate. In total, 12 g of tissue was resected, which demonstrated morphological and immunohistochemical similarities to clear cell carcinoma of the kidney. Ultrasound inspection and computed tomography revealed prostate enlargement. Although no renal-enclosed mass was identified, metastatic lesions were revealed in the lungs, sternum and clavicles. In addition, right pleural thickening and a small amount of effusion in the pleural cavity were detected. Clear cell carcinoma was identified throughout the prostate, with surrounding regions of ordinary-type prostatic adenocarcinoma (Gleason score, 4+4). The urinary bladder exhibited no dysplasia or neoplasia. It was therefore concluded that the tumor represented a primary renal-type clear cell carcinoma that had arisen in the prostate. To the best of our knowledge, this type of extra-renal tumor has only been reported in three other previous studies. PMID- 26137030 TI - Budd-Chiari syndrome, a rare complication of multicentric Castleman disease: A case report. AB - A 39-year-old female presented to The First Affiliated Hospital of Jishou University (Jishou, Hunan) with a fever of unknown origin and progressive abdominal distension. Physical examination revealed generalized lymphadenopathy, multiple non-tender cutaneous nodules, hepatomegaly, splenomegaly and abdominal edema. An axillary lymph node biopsy indicated hyaline vascular type Castleman disease, and color Doppler and computed tomography scans suggested Budd-Chiari syndrome (BCS). Based on the abdominal distension and impairments of the liver and kidneys, an inferior vena cavography and balloon dilatation were performed, confirming the diagnosis of BCS and leading to symptomatic improvement. The patient commenced a combination chemotherapy regimen of cyclophosphamide (0.4 g; days 1-3), vindesine (4 mg; day 1) and prednisolone (100 mg; days 1-5), with no melioration of symptoms. Theprubicin was added to suppress the aggravation of the disease on day six of the chemotherapy cycle. The patient exhibited symptomatic remission for one week, however, she subsequently succumbed to intracranial hemorrhage and infections of the lung and intestine due to long-term myelosuppression following chemotherapy. To the best of our knowledge, this is the first report of BCS in a patient with multicentric Castleman disease without human immunodeficiency virus infection. PMID- 26137031 TI - Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma. AB - The aim of the present study was to determine the expression of a-disintegrin and metalloproteinase 10 (ADAM10) in human glioma tissues from surgical specimens and discuss its possible significance in glioma biology. A total of 43 glioma specimens obtained from patients between 2007 and 2010 were collected and a series of assays were performed. Of these, 22 cases were low-grade gliomas, while 21 cases were high-grade gliomas. In addition, 20 cases of meningioma were used as the control group. Reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunohistochemistry were used to determine the mRNA and protein expression levels of ADAM10. Besides the quantitative analysis, histological observations were also performed to localize ADAM10 expression in glioma cells. The RT-PCR and western blot analysis results demonstrated increased ADAM10 expression in the low-grade glioma samples compared with the control (P<0.05), while ADAM10 expression was further increased in the high-grade glioma samples (P<0.01 vs. control; P<0.05 vs. low-grade glioma), indicating that the mRNA and protein expression levels of ADAM10 were malignancy-dependent. The immunohistochemical analysis revealed that the ADAM10 protein was located on both the tumor cell membrane and blood vessel walls within tumor tissues. In conclusion, these results indicated that ADAM10 expression correlates with the grade of malignancy in human glioma from surgical specimens. In addition, the fact that ADAM10 protein was expressed on cell membranes and blood vessel walls within tumor tissues, indicates that its expression may be associated with invasive tumor growth and peritumoral edema formation. PMID- 26137032 TI - Radiofrequency ablation and percutaneous permanent iodine-125 implantation as salvage therapy for giant recurrent sclerosing epithelioid fibrosarcoma of the chest wall: A case report. AB - Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft-tissue sarcoma for which there is no standardized treatment regimen available. The current treatment options for SEF are resection, radiation and chemotherapy. Surgical resection remains the mainstay of therapy for SEF. However, SEF is an aggressive tumor that is prone to repeated local recurrence if not widely excised. Radiation and chemotherapy are less commonly used due to the insensitivity of SEF to these therapies. The treatment of recurrent SEF is even more challenging. The present study describes a patient who presented with a giant recurrent SEF arising from the chest wall that was accompanied by emergent bleeding. The patient was a 70 year-old male who had multiple comorbid diseases, including hypertension and chronic cardiac dysfunction. A computed tomography (CT) scan indicated the involvement of the sternum and anterior mediastinum. However, the patient refused any further surgery. Subsequent to careful discussion and consideration, radiofrequency (RF) ablation and percutaneous iodine-125 implantation was administered. The emergent bleeding was successfully stopped and the tumor was eliminated using RF ablation. Percutaneous iodine-125 implantation under CT guidance established effective control on the growth of the tumor involving the mediastinum. Despite this, the tumor recurred 6 months after treatment. The patient refused any further treatment and was discharged. In conclusion, RF ablation and percutaneous permanent iodine-125 implantation is a feasible and safe salvage therapy for patients with recurrent SEF of the chest wall. PMID- 26137033 TI - Laparoscopic resection of primary adrenal ganglioneuroma: A case report and review of the literature. AB - Adrenal ganglioneuroma (AGN) is an extremely rare, benign tumor that originates from the neural crest tissue of the sympathetic nervous system. The majority of cases are detected incidentally, since the disease often lacks clear clinical manifestations or is asymptomatic. In addition, AGN is often misdiagnosed as being an adrenal adenoma or adrenal pheochromocytoma. The present study describes a 58-year-old female who visited the outpatient clinic of the Affiliated Hospital of Guangdong Medical College (Zhanjiang, Guangdong, China) with symptoms of face and lower extremity dropsy. Color Doppler ultrasonography revealed a solid tumor in the right kidney, and abdominal computed tomography identified an irregular, solid tumor measuring ~6*4.5*7 cm3 and arising from the right adrenal gland, with a clear boundary. Magnetic resonance imaging was not performed. An initial diagnosis of adrenal adenoma was established. The patient was treated by laparoscopy in order to remove the tumor. However, following surgery, a pathological examination suggested that the tumor was a GN originating from the adrenal medulla. The formation of a correct diagnosis can be extremely challenging, as AGNs do not exhibit any specific clinical manifestations. Therefore, detection often depends entirely upon imaging studies, and the final diagnosis can be only by confirmed following a histopathological evaluation. PMID- 26137034 TI - Lentivirus-mediated RNA interference targeting UbcH10 reduces cell growth and invasion of human osteosarcoma cells via inhibition of Ki-67 and matrix metalloproteinases. AB - Osteosarcoma (OS) is the most commonly diagnosed primary malignancy affecting the bone. UbcH10 is a cancer-related E2-ubiquitin-conjugating enzyme. An overexpression of UbcH10 is significantly associated with tumor grade and cellular proliferation. However, limited evidence exists with regard to the biological function of UbcH10 in OS. The present study created a UbcH10 knockdown OS cell line using lentivirus-mediated RNA interference. The expression of UbcH10 was significantly reduced in UbcH10-targeted small hairpin RNA-expressing lentivirus OS cells. The downregulation of UbcH10 suppressed OS cell proliferation and colony formation ability via decreased Ki-67 expression. UbcH10 knockdown OS cells exhibited impaired invasion and migration abilities. Furthermore, knockdown of UbcH10 led to decreased levels of matrix metalloproteinase-3 and -9 in OS cells. The present study demonstrated the role of UbcH10 in OS cell proliferation, invasion and migration, which suggests that UbcH10 may be a potential candidate for OS therapy. PMID- 26137035 TI - Bone multicentric epithelioid hemangioendothelioma of the lower and upper extremities with pulmonary metastases: A case report. AB - The present study reports a rare case of bone multicentric epithelioid hemangioendothelioma (EH) involving the upper and lower extremities simultaneously, with visceral involvement of the lung. Osteolytic lesions were first identified in the right distal femur and proximal tibia. Slight increased radionuclide uptake was observed in the right shoulder joint on bone scintigraphy, however, this was ignored, as no clinical symptoms were present. The patient was initially misdiagnosed with multifocal chondroblastoma, and an extra-articular curettage of lesions was performed in the proximal tibia and medial femoral condyle, which was filled with bone cement. The histopathological diagnosis was corrected post-operatively following immunohistochemical analysis, which indicated EH, and subsequently, an amputation of the right leg at thigh level was performed. In addition, multiple lytic lesions in the right shoulder joint and pulmonary metastases were identified on whole-body radiological examination. Radiotherapy was administered to the right shoulder joint, however, the patient refused chemotherapy or further surgery. At 15 months after the initial surgery, the patient currently remains alive. This case indicates that an improved understanding with regard to the clinical features of this disease may prevent misdiagnosis and improve EH treatment. PMID- 26137036 TI - Bilateral mammary duct ectasia induced by sulpiride-associated hyperprolactinemia: A case report. AB - A 32 year old female diagnosed with schizophrenia was treated with sulpiride, trihexyphenidyl and alprazolam for 6 years. A physical examination revealed bilateral nipple retraction and a non-tender mass in the left breast, with little nipple discharge. Tests revealed high levels of carbohydrate antigen 125, serum prolactin and testosterone levels, and ultrasound revealed a number of masses in the bilateral breasts; the largest mass (2.2*1.3 cm) was located in the left breast. A rich blood flow signal was identified around the nodule. The ducts in the bilateral breasts exhibited cystic ectasia. Multiple enlarged lymph nodes were found in the bilateral axillae. Mammography revealed thickened breast tissue without an evident mass, and calcification. A segmental mastectomy was performed and subsequent histological examination revealed multiple dilated ducts, the largest of which contained eosinophilic material. The pathological diagnosis was of breast duct dilatation. Bacterial culture and drug sensitivity analysis of the secretions from the cystic cavity revealed no bacterial growth, and an acid fast bacillus stain was negative. Extravasation of the surgical wound occurred 1 month later, and Staphylococcus epidermidis was observed using a bacterial culture. This was treated with moxifloxacin for 1 week. It was suggested that the patient should switch to a prolactin sparing antipsychotic in view of the hyperprolactinemia, however, the patient refused. After a clinical follow-up of 16 months, the wound had healed well and no palpable mass was found in the breast. PMID- 26137037 TI - Gestational choriocarcinoma with uterine serosal metastasis mimicking ruptured ectopic pregnancy: A case report. AB - Primary gestational choriocarcinoma is commonly present in the uterus in cases of atypical genital bleeding. Symptoms similar to those of an ectopic pregnancy develop when an extra-uterine lesion is present in the abdominal cavity, and lesions have been detected in the ovaries and fallopian tubes in a number of cases. In the present study, we describe a patient with choriocarcinoma that metastasized to the uterine serosa and caused symptoms similar to those of an ectopic pregnancy. The patient was a 30-year-old female who presented to our hospital with atypical genital bleeding and a positive pregnancy test 3 months after missed abortion at 10 weeks of gestation. Transvaginal ultrasonography revealed the absence of a gestational sac in or outside the uterus, and intra abdominal bleeding was noted. An ectopic pregnancy was suspected based on these findings, and emergency laparotomy was performed. A hemorrhagic mass was present on the uterine serosa, and was subsequently resected. Trophoblastic disease was suspected following histopathological examination, for which intra-uterine curettage was performed and choriocarcinoma was diagnosed. Lung metastasis was detected on computed tomography, and a high serum human chorionic gonadotropin (hCG) level persisted following surgery. The lesion disappeared following five cycles of methotrexate+ etoposide+actinomycin D therapy, which was performed as postoperative chemotherapy, and the patient's serum hCG level decreased to below the detection limit. In this case of choriocarcinoma, the primary lesion was present in the uterus and had metastasized to the uterine serosa, which is a very rare metastatic site. This uterine serosal metastatic lesion bled and caused symptoms similar to those of an ectopic pregnancy. Certain patients who undergo surgery for a suspected peritoneal pregnancy may have gestational choriocarcinoma, similar to this case. PMID- 26137038 TI - Malignant perivascular epithelioid cell tumor arising in the mesentery: A case report. AB - Primary perivascular epithelioid cell tumors (PEComas) of the mesentery are rare; therefore, the clinical and imaging features of the tumor have yet to be adequately investigated. The present study reports the case of a 48-year-old female patient histologically diagnosed with a PEComa arising in the mesentery of the small bowel. Abdominal plain computed tomography (CT) identified a large, partially ill-defined and heterogeneous mass with a size of 12.5*8.5-cm occupying the lower abdomen. Upon contrast-enhanced CT imaging, the tumor displayed nonhomogeneous contrast-enhancement with hypodense areas, and multiple tumor vessels were observed during arterial phase imaging. In conclusion, the present study proposed that PEComas should be considered in the differential diagnosis of lesions arising in the mesentery; however, differentiation based on imaging criteria alone can be difficult. PMID- 26137039 TI - Efficacy of recombinant adenoviral human p53 gene in the treatment of lung cancer mediated pleural effusion. AB - Pleural effusion induced by lung cancer exerts a negative impact on quality of life and prognosis. The aim of the present study was to evaluate the value of the recombinant adenoviral human p53 gene (rAd-p53) in the local treatment of lung cancer and its synergistic effect with chemotherapy. The present study retrospectively recruited 210 patients with lung cancer-mediated pleural effusion who had adopted a treatment strategy of platinum chemotherapy. Pleurodesis was performed via the injection of cisplatin or rAd-p53. Long-term follow-up was conducted to investigate the therapeutic effects of cisplatin and rAd-p53 administration on pleural effusion and other relevant clinical indicators. The short-term effect of pleurodesis was as follows: The efficacy rate of rAd-p53 therapy was significantly higher compared with cisplatin therapy (71.26 vs. 54.47%), and the efficacy of treatment with >=2*1012 viral particles of rAd-p53 for pleurodesis was significantly greater than treatment with 40 mg cisplatin (P<0.05). Furthermore, efficacy analysis performed 6 and 12 months after pleurodesis indicated that the efficacy rate of rAd-p53 was significantly greater than that of cisplatin (P<0.05). A comparison of median progression-free survival (PFS) time identified a significant difference (P<0.05) between rAd-p53 and cisplatin therapy (3.3 vs. 2.7 months); however, a comparison of median overall survival time identified no significant difference (P>0.05) between rAd-p53 and cisplatin therapy (9.6 vs. 8.7 months). In addition, Cox regression analysis indicated that PFS was not affected by clinical indicators such as age, gender, prognostic staging and smoking status; however, PFS was affected by pathological subtype (adenocarcinoma or squamous carcinoma) in the rAd-p53 group. rAd-p53 administration for pleurodesis exerts long-term therapeutic effects on the local treatment of lung cancer. Thus, a combination of rAd-p53 and chemotherapy may exert a synergistic effect and reverse multidrug resistance. PMID- 26137040 TI - Ex vivo hepatectomy and partial liver autotransplantation for hepatoid adenocarcinoma: A case report. AB - We previously reported the case of a 56-year-old male who underwent surgical treatment for gastric hepatoid adenocarcinoma and splenic metastasis. The present study reports the case of the same patient who underwent successful ex vivo hepatectomy and partial liver autotransplantation. Computed tomography scans demonstrated that the tumor was located in the left and caudate lobes of the liver, with hepatic vein and inferior vena cava involvement, and right portal vein compression. To clarify the association between the vessels and the tumor, a three-dimensional imaging technique was used to reconstruct the liver architecture. During the surgery, the whole liver was removed with the retrohepatic vena cava, which was replaced with a prosthetic graft without a veno venous bypass; a portacaval shunt for the anhepatic phase was performed simultaneously. The surgery lasted 9 h, and the anhepatic phase lasted 4 h. Blood loss during the surgery was recorded at 1,500 ml. The time taken for recovery was 21 days post-surgery, and at 20 months, the patient was disease-free. To the best of our knowledge, this is the first case of ex vivo liver resection performed for hepatic metastasis of hepatoid adenocarcinoma to be reported. PMID- 26137041 TI - Primary signet-ring cell carcinoma of the lung treated with crizotinib: A case report. AB - Primary signet-ring cell adenocarcinoma (SRCA) of the lung is an extremely rare subtype of lung adenocarcinoma with a poor prognosis. The presence of an SRC component is considered to be a prominent clinicopathological characteristic of EML4-ALK-positive non-small cell lung cancer (NSCLC). Crizotinib, an anaplastic lymphoma kinase inhibitor, has been approved for the treatment of EML4-ALK NSCLC by previous studies, but its effect on SRCA, an extremely rare subtype of lung adenocarcinoma, has yet to be elucidated. Therefore, the present study aimed to evaluate the clinical response of SRCA to crizotinib, and examine the potential use of crizotinib as a treatment for the carcinoma. A 43-year-old male was admitted to the Qingdao Municipal Hospital (Qingdao, China) with dyspnea. Chest computed tomography (CT) revealed a mass in the middle lobe of the right lung. Transbronchial lung biopsies revealed the presence of SRCA (70%) mixed with poorly-differentiated adenocarcinoma (30%). Immunohistochemically, the SRCA cells were positive for cytokeratin (CK)7 and thyroid transcription factor-1, and negative for CK20. An inversion of the EML4-ALK gene was detected by fluorescence in situ hybridization and crizotinib was injected by nasogastric tube. The patient was highly responsive to crizotinib. The symptoms of dyspnea were relieved and the volumes of pericardial and pleural effusion were gradually reduced. A CT scan revealed lung tumor regression. The overall response was a partial response. Therefore, crizotinib exists an attractive therapeutic option for patients with SRCA. However, in the present study, acquired drug resistance to crizotinib developed after only one month of treatment. It would consequently be valuable to investigate the mechanisms underlying acquired crizotinib resistance in future studies. PMID- 26137042 TI - Concurrent chronic neutrophilic leukemia blast crisis and multiple myeloma: A case report and literature review. AB - The current study presents the case of a 78-year-old male with concurrent chronic neutrophilic leukemia (CNL) and multiple myeloma (MM) who developed acute myeloid leukemia after two years of treatment with hydroxyurea, cyclophosphamide, prednisone and thalidomide. The patient presented with mature neutrophilic leukocytosis, hepatosplenomegaly, a high neutrophil alkaline phosphatase score and an absence of the Philadelphia chromosome or the BCR-ABL fusion gene. A bone marrow aspirate smear and biopsy indicated that the CNL coexisted with a plasma cell neoplasm. In addition, monoclonal lambda-paraproteinemia was detected by serum protein immunofixation electrophoresis, and bone lesions were identified in multiple vertebrae. The patient achieved complete remission following one cycle of induction chemotherapy with the decitabine regimen in combination with the low dose cytarabine, aclarubicin and granulocyte-colony stimulating factor (CAG) priming regimen. The occurrence of CNL and MM concurrently is extremely rare and thus, it has only been reported in a small number of cases. The occurrence of CNL and MM in the same patient as two distinct hematological malignancies indicates the neoplastic transformation of a pluripotent stem cell. Decitabine combined with the CAG priming regimen may present a good therapeutic strategy for elderly patients with secondary acute myeloid leukemia. PMID- 26137043 TI - Downregulation of human epidermal growth factor receptor 2 by short hairpin RNA increases chemosensitivity of human ovarian cancer cells. AB - The aim of the current study was to investigate the suppressive effects of pSilencer T7-human epidermal growth factor receptor 2 (HER2)-short hairpin RNA (shRNA) recombinant plasmids on human SKOV3 ovarian cancer cell growth and sensitivity to carboplatin (CBP). Three different pairs of shRNAs (shRNAa, shRNAb and shRNAc), targeting the HER2 gene, were selected and transfected into human SKOV3 cells, respectively. The expression levels of HER2 were then detected by immunohistochemical (IHC), semi-quantitative reverse transcription-polymerase chain reaction and western blot analyses. In addition, cell cycle and cell growth were investigated using cell counting kit-8 (CCK-8). The results of the IHC and western blot analyses revealed that shRNAb significantly inhibited HER2 protein expression in SKOV3 cells. shRNAb exhibited an improved effect on HER2 expression compared with shRNAa (P<0.01), while shRNAc did not affect HER2 expression. Nontransfected and nonspecific shRNA groups were used as the negative controls. Knockdown of HER2 expression by shRNA was initiated at 24 h following transfection, achieving an optimum effect at 48 h and lasting for at least 72 h after the treatment. The CCK-8 cell growth assay indicated that the knockdown of HER2 expression in the SKOV3 cell line resulted in significant growth suppression and cell cycle arrest. In addition, inhibition of HER2 significantly increased SKOV3 cell sensitivity to CBP treatment. In conclusion, pSilencer T7-HER2-shRNA significantly inhibited HER2 expression in human ovarian cancer cells in vitro and induced chemotherapeutic sensitivity to CBP. PMID- 26137044 TI - Tumor size and lymph node status determined by imaging are reliable factors for predicting advanced cervical cancer prognosis. AB - The aim of the present study was to investigate the prognostic role of a number of clinical factors in advanced cervical cancer patients. Patients (n=157) with stage IIA-IIB cervical cancer treated at four Hallym Medical Centers in South Korea (Hallym University Sacred Heart Hospital; Kangnam Sacred Heart Hospital; Chuncheon Sacred Heart Hospital; and Kangdong Sacred Heart Hospital) between 2006 and 2010 were retrospectively enrolled. Univariate analysis identified significant predictive values in the following eight factors: i) Cancer stage (P<0.0001); ii) tumor size (<=4 vs. 4-6 cm, P=0.0147; and <=4 vs. >6 cm, P<0.0001); iii) serum squamous cell carcinoma antigen level (<=2 vs. >15 ng/ml; P=0.0291); iv) lower third vaginal involvement (P<0.0001); v) hydronephrosis (P=0.0003); vi) bladder/rectum involvement (P=0.0015); vii) pelvic (P=0.0017) or para-aortic (P=0.0019) lymph node (LN) metastasis detected by imaging vs. no metastasis; and viii) pelvic LN metastasis identified by pathological analysis (P=0.0289). Furthermore, multivariate analysis determined that tumor size (<=4 vs. 4-6 cm, P=0.0371; and <=4 vs. >6 cm, P=0.0024) and pelvic LN metastasis determined by imaging vs. no metastasis (P=0.0499) were independent predictive variables. Therefore, tumor size and pelvic LN metastasis measured by imaging were independent predictive factors for the prognosis of advanced cervical cancer. These factors may provide more clinically significant prognostic information compared with the currently used International Federation of Gynecology and Obstetrics staging system. PMID- 26137046 TI - Ovarian cancer transformation from adenocarcinoma to undifferentiated small cell carcinoma: A case report. AB - The ovaries contain cells that have the capacity for regeneration and cancer stem cells (CSC) that are capable of differentiating aberrantly from the homeostatic controls. The histology of ovarian cancer does not usually change in a patient. However, CSCs are the origin of a number of tumors. CSCs are known to exist in ovarian carcinomas and the expression of CD44, c-Kit and CD133 has been identified in such carcinomas. This study presents the case of a patient diagnosed with ovarian cancer with an abdominal mass who underwent surgery, eight cycles of gemcitabine-paclitaxel chemotherapy and irradiation. Pathological examination indicated a transformation from adenocarcinoma to undifferentiated small cell carcinoma. The expression of CD133 changed from negative to positive in ovarian carcinomas. The present case indicates that any histological changes observed in ovarian neoplasms originate from neoplastic stem cells. In addition, this case demonstrates the importance of repeatedly assessing therapy by tumor biopsy throughout the course of ovarian cancer treatment. PMID- 26137045 TI - microRNA-126 suppresses PAK4 expression in ovarian cancer SKOV3 cells. AB - Primary ovarian cancer is one of the predominant causes of mortality from gynecological cancer. The suppression of serine/threonine p21-activated kinases (PAKs), proteins involved in cell morphology and cytoskeletal reorganization, has been hypothesized to improve the survival of patients with ovarian cancer. However, the association between microRNA-126 (miR-126) and PAK4 in the inhibition of ovarian cancer cell invasion remains to be established. The present study demonstrated changes in the level of PAK4 expression in ovarian cancer SKOV3 cells with altered miR-126 compared with normal SKOV3 cells. The SKOV3 cells that were transfected with LV3-miR-126 to increase miR-126 expression exhibited significantly downregulated expression levels of PAK4 (P<0.05), whilst transfection with the LV3-hsa-miR-126 inhibitor increased the expression of PAK4 in these cells (P<0.05), as assessed by immunofluorescence staining. Furthermore, western blot analysis revealed a significant increase in PAK4 expression in the SKOV3 cells transfected with the LV3-hsa-miR-126 inhibitor, and a decrease in those transfected with LV3-hsa-miR-126. The present study provides an experimental foundation for miR-126 as a potential tumor suppressor that may decrease PAK4 expression to inhibit ovarian cancer cells. PMID- 26137047 TI - Inflammatory myofibroblastic tumor of the urinary bladder during pregnancy: A case report. AB - A 31 year-old pregnant female who had not menstruated for 31 weeks presented to The Affiliated Hospital of Chifeng College (Chifeng, China) with painless gross hematuria, which had been present for 10 days. A computed tomography scan revealed a tumor of 5.8*6.3 cm in diameter. A biopsy was not obtained prior to surgery. Following the initial workup, the patient underwent a cesarean section and partial cystectomy of bladder. Pathological examination revealed inflammatory myofibroblastic tumor (IMT). An initial cytoscope examination was performed one year after surgery, with subsequent follow-up cystoscope examinations performed every three months, and at the time of writing the patient was alive, with no evidence of tumor recurrence. IMT of the urinary bladder is a rare benign lesion and to the best of our knowledge, this is the first reported case describing IMT of the urinary bladder during pregnancy. This study describes the process of diagnosis and management of the patient. PMID- 26137048 TI - Carcinoid tumor arising in a mature cystic teratoma: A case report. AB - Mature cystic teratomas are common benign tumors of the ovary. The most common form of malignant transformation is squamous cell carcinoma, however, malignant transformation is rarely observed and cases are usually asymptomatic. Carcinoid tumors are rare tumors of the neuroendocrine system. A number of the carcinoids result in clinical syndromes due to the secretion of vasoactive substances produced by the tumor. A 75-year-old woman suffering from groin pain was admitted to the Faculty of Medicine at Bezmialem Vakif University (Istanbul, Turkey). An adnexal mass was detected during the physical examination. Magnetic resonance imaging scans exhibited an 8*7-cm mass in the right ovary. Surgical excision of the mass was performed and histopathological examination revealed a mature cystic teratoma with three germ layers. An area consisting of nests and trabeculae was evident in the cyst wall. The pathological diagnosis was of an insular and trabecular variant of carcinoid tumor arising in a mature cystic teratoma. The patient did not present with carcinoid syndrome, and no recurrence was observed after 11 months of follow-up examinations. PMID- 26137049 TI - Epidermal growth factor receptor mutation heterogeneity analysis of pulmonary sarcomatoid carcinoma successfully treated with erlotinib: A case report. AB - Pulmonary sarcomatoid carcinoma (PSC) is a rare histological subtype of non-small cell lung cancer, and the available studies on the response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is limited. In the present study, a 73-year-old female presented with a large mass in the lower right lung, which was diagnosed as a PSC on biopsy. An amplification-refractory mutation system (ARMS) test revealed that the patient possessed the wild-type EGFR gene, and the patient subsequently underwent radiotherapy (60 Gy) and four 21-day cycles of chemoradiotherapy (1,600 mg gemcitabine, days 1 and 8; 30 mg, cisplatin, days 1-3). Following radiotherapy and chemotherapy treatment, a CT scan revealed complete remission of the mass in the lower right lung, however, metastases were identified in the paraaortic lymph node, bilateral iliac fossa and the right gluteal region. Notably, an EGFR exon 21 L858R gene mutation was identified in the mass of the right gluteal metastasis. Therefore, treatment with erlotinib was initiated. The patient continued to experience progression-free survival for six months following the initiation of erlotinib therapy. However, multiple metastases were then identified, and all lesions possessed the wild-type EGFR gene, as identified by the ARMS test. The findings suggest that erlotinib is a viable therapeutic option for the treatment of PSC patients that possess an EGFR mutation. The spatio-temporal evolution of EGFR mutational heterogeneity in PSC may result in drug-resistance, which challenges EGFR-TKI therapy and EGFR gene mutation diagnosis. PMID- 26137050 TI - Clinical characteristics and laboratory analyses of acute myeloid leukemia with t(16;21)(p11;q22). AB - The present study reviewed three patients with acute myeloid leukemia (AML) who had the specific genetic abnormality t(16;21)(p11;q22). To investigate the clinical and laboratory characteristics of AML with t(16;21)(p11;q22) translocation, the similarities and differences of clinical characteristics and laboratory examinations were compared, and a literature review was conducted. According to the French-American-British classification system, patient 1 was M4, patient 2 was M1 and patient 3 was M2. The cytogenetic aberrations were 46, XY, t(16;21)(p11;q22)/47, idem, +21 for patient 1 and 46, XX, t(16;21)(p11;q22) for patients 2 and 3. Cytophagocytosis and cluster of differentiation 56 antigen expression were found in all three cases. The prognosis was poor in all the cases. AML with t(16;21)(p11;q22) is a specific subtype of AML that exhibits unique characteristics of morphology, immunology, cytogenetics and clinical features, as well as a poor prognosis. Stem cell transplantation may be the first and only choice for treatment. PMID- 26137051 TI - Artesunate altered cellular mechanical properties leading to deregulation of cell proliferation and migration in esophageal squamous cell carcinoma. AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer in China. Artesunate (ART) is used clinically as an anti-malarial agent and exhibits potent antiproliferative activity. In addition, ART has demonstrated remarkable antitumor activity, presenting a novel candidate for cancer chemotherapy. However, its effect on ESCC remains unknown. The present study analyzed the antitumor effects of ART in the KYSE-150 ESCC line by assessing cell proliferation, cell death, cell migration/invasion and the biomechanical properties of ART-treated KYSE-150 cells. ART treatment significantly suppressed the proliferation of KYSE-150 cells in a dose- and time-dependent manner, as assessed by MTT assay. Following treatment with 30 mg/l ART, the cell population in the G0/G1 phase and the level of cell apoptosis significantly increased from 54+/-1.5 to 68.1+/-0.3%, and from 4.53+/-0.58 to 12.45+/-0.62%, respectively. Furthermore, the cell migration and invasion of KYSE-150 cells treated with 30 mg/l ART was markedly inhibited. The cell membrane and biomechanical properties were investigated using atomic force microscopy, as targets of ART action. ESCC cells treated with 30 mg/l ART exhibited increased adhesive force, increased cytomembrane roughness and reduced elasticity compared with the control group (KYSE-150 cells without ART treatment). The biomechanical properties of KYSE-150 cells treated with 30 mg/l ART were similar to those of the SHEE normal human esophageal epithelial cell line. In conclusion, the present study demonstrated that ART may inhibit cell proliferation and migration in ESCC through changes in the biomechanical properties of the ESCC cells. PMID- 26137052 TI - Imaging features of primary hepatic leiomyosarcoma: A case report and review of literature. AB - Primary hepatic leiomyosarcoma (PHL) is an extremely rare tumour. This tumour is difficult to diagnose by imaging examinations due to its rarity, and non-specific conventional imaging manifestations and clinical presentation. The present study reports the case of a 42-year-old male with PHL that was confirmed by histopathological and immunohistochemical examinations. Multimodal imaging examinations, including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT and digital subtraction angiography, were performed. The imaging manifestations were analysed and the associated literature was reviewed. The results found that no characteristic imaging appearance was present on ultrasound or plain CT scan. However, on unenhanced MRI, the tumours presented with a heterogeneous low signal density on T1-weighted imaging (WI) and a high signal density on T2WI and diffusion-WI. On gadopentetate dimeglumine enhanced MRI, the lesions were not enhanced during the arterial and portal venous phases; by contrast, these lesions were evidently enhanced during the 5-min delayed phase. Therefore, the delayed imaging of enhanced MRI is likely to be used to differentiate PHL from other hepatic tumours. PMID- 26137053 TI - Demethylation of microRNA-142 induced by demethylation agents plays a suppressive role in osteosarcoma cells. AB - Osteosarcoma (OS), the most common malignant bone tumor, occurs mainly in adolescents and young adults, with a morbidity of ~5 cases per million. The expression levels of microRNAs (miRNAs) as tumor suppressors were recently found to be downregulated in OS. Certain alterations of miRNAs and the possible mechanisms through which miRNAs affect cell proliferation and migration in OS were recently found to be correlated with methylation epigenetic mechanisms. In this study, it was demonstrated that, due to hypermethylation, the expression level of miRNA-142 (miR-142) was significantly downregulated in OS tissues and cells compared with that in control samples. The present study demonstrated an increased expression of miR-142 in Saos-2 and MG63 cells treated with demethylation agents, suggesting that the effect of such agents on cell growth, inhibition of invasion and cell cycle retardation may be mediated by miR-142 in OS. PMID- 26137054 TI - Expression and significance of glucose-regulated protein 78 in human osteosarcoma. AB - The present study aimed to investigate the expression of glucose-regulated protein 78 (GRP78) in osteosarcoma cells, and analyze the differences in expression between tumor and normal tissues, pre- and post-chemotherapy patients and metastatic and non-metastatic tumors. According to these results, the associations between the expression of GRP78 and tumor growth, metastasis and chemotherapeutics could be determined. Between 2007 and 2012, 60 patients who had been diagnosed with osteosarcoma were selected for the present study. Of these patients, 20 presented with non-metastatic tumors and 40 with metastatic tumors, and 20 had been treated without chemotherapy and 40 with chemotherapy. In addition, 60 specimens obtained from adjacent normal tissues were collected for the control groups. Immunofluorescence staining was used to examine the expression of GRP78 in the different tissues. The total RNA and protein were extracted from crushed tissues and used in the reverse transcription polymerase chain reaction and western blot analysis. GRP78 was primarily located in the intracavity of the endoplasmic reticulum. The expression level of GRP78 in the tumor tissue was higher than that in the normal tissue surrounding the tumor (P<0.01). In addition, the level was higher in the metastatic tumors compared with the non-metastatic tumors (P<0.05), and in the non-chemotherapy-treated patients compared with the chemotherapy-treated patients (P<0.01). The expression level of GRP78 mRNA in the tumor tissue was higher than that in the normal tissue (P<0.01). Furthermore, the level was higher in the metastasis group than in the non-metastasis group (P<0.05), and in the non-chemotherapy group than in the chemotherapy group (P<0.01). The expression level of GRP78 protein was higher in the tumor tissue compared with the normal tissue (P<0.01), in the metastasis group compared with the non-metastasis group (P<0.05), and in the non chemotherapy group compared with the chemotherapy group (P<0.01). In conclusion, the present study detected the expression of GRP78 in patients with osteosarcoma and revealed a higher expression level in the tumor tissues compared with the normal tissues around the tumor, in the metastasis group compared with the non metastasis group and in the non-chemotherapy-treated group compared with the chemotherapy-treated group. PMID- 26137055 TI - Cutaneous syncytial myoepithelioma: A case report with emphasis on the differential diagnosis of problematic dermal tumors. AB - Cutaneous myoepithelioma is a peculiar and recently recognized neoplasm exhibiting purely myoepithelial differentiation. These lesions affect different areas of the body, and are characterized by heterogenous morphological and immunophenotypical features. The majority of cutaneous myoepitheliomas behave in a benign fashion, however, the risk for local recurrence is higher with incomplete resection. A relatively newly described variant of myoepithelioma exhibits syncytial cytological features. The current study reports a case of cutaneous syncytial myoepithelioma presenting as a painless and papular skin lesion. The presence of the Ewing sarcoma RNA-binding protein 1 gene rearrangement in the present case supported the diagnosis of a myoepithelial tumor. The patient subsequently underwent local excision of the tumor and was followed up twice in the year after surgery. At the time of writing, the patient was alive and no recurrences had been identified. Furthermore, the current study discusses how this myoepithelial neoplasm may be distinguished from other problematic spindle or epithelioid cell tumors, particularly superficial dermal lesions. PMID- 26137056 TI - Inhibition of autophagy promotes cell apoptosis induced by the proteasome inhibitor MG-132 in human esophageal squamous cell carcinoma EC9706 cells. AB - Lysosome-dependent macroautophagy, also termed autophagy, and the ubiquitin proteasome system and are the primary intracellular pathways involved in protein degradation. Previous studies have demonstrated that proteasome inhibitors are able to inhibit tumor growth and activate autophagy. The present study investigated the effect of the proteasome inhibitor MG-132 on cellular proliferation using a cell counting kit 8 assay, and the effect of the agent on apoptosis and autophagy was assessed using flow cytometry and monodansylcadaverine, respectively. Western blot analysis was used to investigate protein changes during the course of treatment. It was revealed that MG-132 inhibited cell proliferation, activated autophagy and induced cell death in EC9706 cells. Autophagy was activated through the class III PI3K pathway, and the expression of the Beclin-1 protein was determined to be significantly upregulated. However, the autophagy inhibitor 3-methyladenine (3-MA) inhibited the expression of the autophagy-associated protein Beclin-1 and reduced the accumulation of autophagic vacuoles induced by MG-132. MG-132-induced apoptosis was enhanced by the autophagy inhibitor 3-MA, which may be a result of caspase-3 activation in the EC9706 cells. These findings suggest that inhibition of the proteasome can induce autophagy in human ESCC cells, and also increase cell death. This indicates that proteasome inhibitors may be potential novel anti cancer agents for the adjuvant treatment of esophageal squamous cell carcinoma. PMID- 26137057 TI - Anti-proliferative action of IL-6R-targeted antibody tocilizumab for non-small cell lung cancer cells. AB - In the present study we analyzed the anti-proliferative effect of tocilizumab, a humanized recombinant monoclonal interleukin 6 receptor (IL-6R) antibody, against non-small cell lung cancer (NSCLC) cells, including A549, H460, H358 and H1299 cells. The cell cycle distribution of NSCLCs was analyzed using fluorescence activated cell sorting and gene expression using quantitative polymerase chain reaction. Cell lysates treated with tocilizumab were immunoblotted with antibodies against signal transducer and activator of transcription 3 (STAT3), phospho-STAT3, extracellular-signal-regulated kinases (ERK), phospho-ERK, nuclear factor kappaB (NFkappaB) and phospho-NFkappaB. Significant growth inhibition of NSCLC cells was observed following treatment with tocilizumab. Proliferation was significantly decreased by approximately 10-40% in A549, H460, H1299 and H358 cells, with an inhibition rate that was comparable with that of the typical anticancer drugs methotrexate and 5-fluorouracil. NSCLC cell populations were accumulated in the sub-G1 phase by treatment with tocilizumab. Western blot analyses revealed a possible activation of the NFkappaB pathway by tocilizumab. Overall, these data indicate that tocilizumab has anticancer potency via apoptosis induction as an agonistic IL-6R regulator. Therefore, we suggest that this anti-IL-6R antibody may be utilized as a new targeting molecule for NSCLC therapies. PMID- 26137058 TI - Hepatic abscess with hepatobronchial fistula following percutaneous radiofrequency ablation for hepatocellular carcinoma: A case report. AB - Radiofrequency ablation (RFA) has a low rate of complication and is one of the most effective and minimally invasive techniques for the treatment of liver tumors. However, a number of complications may occur in rare cases, including bronchobiliary fistula, hollow viscera perforation, diaphragmatic perforation and hernia. The present study reports a case of hepatic abscess with hepatobronchial fistula following RFA of hepatocellular carcinoma; this led to severe lung infection, respiratory failure and mortality. The present case report aims to improve understanding of the cause and mechanism of the complications arising through RFA of the liver, and highlight important factors in the prevention and management process. This case indicates that the complications of RFA may be prevented or effectively managed through preoperative evaluation, intraoperative and postoperative monitoring. PMID- 26137059 TI - Adult pancreatoblastoma: A case report and review of the literature. AB - The present study describes the case of a 24-year-old patient who presented with obstructive jaundice and weight loss, and was diagnosed with pancreatoblastoma (PB). Abdominal imaging studies revealed a heterogenous lesion of the pancreatic head with dilatation of the common bile duct. The patient underwent pancreaticoduodenectomy, however, three months after surgery multiple liver and bone metastases were identified on follow-up computed tomography scans. Despite treatment with four cycles of systemic chemotherapy and five courses of radiofrequency ablation, the patient succumbed due to tumour dissemination 13 months after initial diagnosis. PB is a malignant tumour of the pancreas that typically occurs in the pediatric population. The aim of the present study was to highlight the aggressive behavior of this rare clinical entity, focusing on the pitfalls of pre-operative diagnosis and the lack of management strategy guidelines in adults. Preoperative diagnosis of PB based on radiographic features may be difficult, as the imaging characteristics are non-specific. Furthermore, cytology may also be misleading, as the neoplasm consists of multiple cell lines (acinar, ductal and neuroendocrine cells) and diagnosis depends largely on the identification of the distinctive histological characteristic of squamoid corpuscles, which present as nests of flattened cells with a squamous appearance. Despite the use of surgical resection and adjuvant chemoradiotherapy for the treatment of this malignancy, its aggressive nature means that PB is associated with a poor prognosis in adult patients. PMID- 26137060 TI - Expression of the tumor suppressor gene hypermethylated in cancer 1 in laryngeal carcinoma. AB - Hypermethylated in cancer 1 (HIC1) is a putative suppressor gene, cooperating with TP53 in the regulation of apoptosis. The promoter site of this gene contains CpG islands susceptible to methylation. Altered methylation leads to the silencing of HIC1. Persistent loss of HIC1 function reflects the attenuation of proapoptotic characteristics of TP53 and may constitute the background for carcinogenesis. Altered methylation profiles along with diminished expression of HIC1 were documented in a number of solid neoplasms. The aim of this study was to evaluate the expression of the HIC1 gene in laryngeal carcinoma. RNA was extracted from samples of laryngeal cancer and corresponding healthy tissues of 21 patients with advanced laryngeal cancer (T3-T4). The amount of RNA (cDNA) was evaluated using reverse transcription-quantitative polymerase chain reaction with GADPH as the reference gene. Data demonstrated that HIC1 expression was significantly reduced in laryngeal cancer tissues. The relative expression of HIC1 was found to be ~40% lower in tumor samples compared to that in healthy controls. The median tumor/normal tissue ratio for HIC1 was 0.615. These results suggest that low HIC1 expression may be associated with neoplastic transformation in the larynx. PMID- 26137061 TI - Apoptosis induced in MCF-7 human breast cancer cells by 2',4'-dihydroxy-6-methoxy 3,5-dimethylchalcone isolated from Eugenia aquea Burm f. leaves. AB - During a previous study that aimed to identify anticancer agents within primate consumed plants, the present group identified that Eugenia aquea (E. aquea) possessed potential as a source of anticancer agents. The ethanol extract of E. aquea leaves exhibited strong inhibitory activity against the proliferation of the human breast adenocarcinoma MCF-7 cell line. The inhibition of proliferation was determined using an MTT assay. The present study was performed to isolate the active compound within the E. aquea leaves that generated the aforementioned activity, and resulted in the isolation of 2',4'-dihydroxy-6-methoxy-3,5 dimethylchalcone, which was identified through the analysis of spectroscopic data. This compound was examined for its inhibitory activity against the MCF-7 cell line using a MTT assay, and the ability of 2',4'-dihydroxy-6-methoxy-3,5 dimethylchalcone to induce apoptosis through the activation of the poly(adenosine diphosphate-ribose) polymerase (PARP) protein was also investigated. The results of the present study revealed that the isolated compound inhibited cell proliferation in a dose-dependent manner, possessed an IC50 of 74.5 ug/ml (250 uM) and promoted apoptosis via the activation of PARP. It was concluded that these results indicated a requirement for additional investigations into 2',4' dihydroxy-6-methoxy-3,5-dimethylchalcone in order to provide a basis for the use of this compound in the management of cancer. PMID- 26137063 TI - Surface-enhanced laser desorption ionization time-of-flight mass spectrometry used to screen serum diagnostic markers of colon cancer recurrence in situ following surgery. AB - The aim of the present study was to identify specific serum biomarkers in patients with colon cancer recurrence in situ following surgery. The study was conducted at the Renmin Hospital of Wuhan University (Wuhan, China) between January 2012 and January 2014. Surface-enhanced laser desorption ionization time of-flight mass spectrometry was used to compare and analyze the serum protein profiles of patients with (n=50) and patients without (n=50) recurrence in situ. Biomarker Wizard software was used to analyze and obtain the protein spectrum. In total, nine protein peaks demonstrated statistically significant differences between the recurrence and non-recurrence group (P<0.05), which included two protein peaks (7,731.3 Da and 8,266.5 Da). The two protein peaks were highly expressed in patients with colon cancer recurrence in situ following surgery, but lowly expressed in patients without recurrence. Therefore, the two protein peaks may represent potential biomarkers for the prediction of colon cancer recurrence in situ following surgical treatment. PMID- 26137062 TI - Overexpression of DNA methyltransferase 1 as a negative independent prognostic factor in primary gastrointestinal diffuse large B-cell lymphoma treated with CHOP-like regimen and rituximab. AB - The aims of the present study were to elucidate the transcript levels of DNA methyltransferase (DNMT)1, DNMT3a and DNMT3b by quantitative polymerase chain reaction in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL), and determine the association of their expression with the clinical parameters and prognostic values of the disease. The results revealed that the expression of DNMT1 in patients with PGI-DLBCL was significantly higher than that in healthy controls (P=0.04), while the expression of DNMT3a and DNMT3b were significantly lower (P<0.001 and P=0.001, respectively). The increased expression of DNMT1 was significantly correlated with shorter overall survival and progression-free survival rates (P=0.018 and P=0.008, respectively). The multivariate analysis demonstrated that the level of DNMT1 was an independent prognostic factor. In conclusion, DNMT1 was identified to be an independent prognostic factor for predicting the survival of patients with PGI-DLBCL; this suggests that it could be used as a marker to indicate the prognosis of PGI DLBCL. PMID- 26137064 TI - Expression and clinical significance of the microRNA-200 family in gastric cancer. AB - Gastric cancer is one of the most common malignant tumors and one of the leading causes of cancer-related mortality. Recent studies have revealed that there is a difference in microRNA (miR/miRNA) profiles between cancerous and normal tissues. To find a potentially useful prognostic predictor and a promising therapeutic tool for gastric cancer, the present study investigated the expression and clinical significance of the miR-200 family in gastric cancer. The miR-200 family has five members: hsa-miR-200a, hsa-miR-200b, hsa-miR-200c, hsa-miR-141 and hsa miR-429. In 46 clinical samples of gastric cancer and paired non-cancerous tissues, the present study observed that the expression levels of the miR-200 family in the cancer tissues were significantly lower than those in the non cancerous tissues (P<0.001). Lower levels of the five family members were associated with histological grade and the presence of an intravascular cancer embolus (P<0.05). The results revealed that the miR-200 family is downregulated in gastric cancer, and that there are significant differences in the expression of the miR-200 family between normal and cancer tissues. The miR-200 family may therefore become a potentially useful prognostic predictor of the aggressiveness of gastric cancer and a possible therapeutic tool in affected patients. PMID- 26137065 TI - Delayed neurological deterioration with an unknown cause subsequent to surgery for intraspinal meningiomas. AB - Delayed neurological deterioration in the absence of direct cord insult following surgical decompression is rare, but severe post-operative complication occurs in chronically compressive spinal disorders. In the present study, the clinical medical records and radiological findings of 10 patients who underwent surgical removal of intraspinal meningiomas and then experienced delayed post-operative neurological deterioration were reviewed. The cases are presented with consideration of the possible underlying mechanisms. There were five male and five female patients, with a mean age of 46.8 years. The mean duration of illness from the onset of symptoms to diagnosis was 42.8 months. Seven tumors were located in the thoracic region and three in the cervical region of the spine. The tumors compressed the cord severely and gross total removal was achieved in all cases. Immediately subsequent to the surgery, all patients were able to move all extremities, but the onset of the neurological deterioration occurred at post operative hours 3-8 in all cases (mean, 5 h post-surgery). In four cases, radiological examination revealed an area of high signal changes intrinsic to the cord on T2-weighted images, but without residual compression. The mean follow-up period was 49.6 months. Nine patients reported a marked recovery in status compared with the pre-operative presentation during the several weeks to months following surgery. The surgical removal of intraspinal meningiomas may lead to delayed and severe neurological deterioration in the post-operative period in the absence of direct mechanical cord insult. Ischemia-reperfusion injury may be one potential etiology of this deterioration. Recognition of the neurological deficit following surgical excision of intraspinal meningiomas may improve pre-operative patient counseling and merits further study for the determination of the precise pathophysiology. PMID- 26137066 TI - Effect of the microtransplantation of allogeneic hematopoietic stem cells as maintenance therapy for elderly patients with acute leukemia. AB - The incidence of acute myeloid leukemia (AML) increases with age. Elderly patients with AML are less tolerant to high-intensity consolidation therapy than younger patients, with significantly worse prognoses. Induction and consolidation therapy combined with allogeneic hematopoietic stem cell microtransplantation may improve the prognosis of elderly patients with AML. The present study reports the effect of maintenance therapy with low-dose chemotherapy treatment combined with microtransplantation in elderly patients with AML following consolidation. Between January 2011 and April 2014, three elderly patients (>55 years old), including one 58-year-old patient with acute mixed lineage leukemia (AMLL) and two patients with AML aged 59 years and 62 years, underwent microtransplantation maintenance therapy. Following a complete response to induction chemotherapy and consolidation chemotherapy with two to four cycles of medium dose Ara-c (auto transplantation was performed in the patient with AMLL), maintenance therapy was performed using low-dose Ara-c combined with human leukocyte antigen haploidentical allogeneic hematopoietic stem cell microtransplantation, which was repeated every 3 to 6 months. The patients were followed up for 27, 20 and 16 months, respectively, and all three patients achieved disease-free survival. The bone marrow Wilms' tumor suppression gene (WT1) level of the case with AMLL was dynamically monitored. The results showed that the WT1 level was abnormally high prior to microtransplantation and gradually declined to normal levels subsequent to the process. None of the patients suffered from graft versus host disease during the microtransplantation process. In conclusion, microtransplantation maintenance therapy following consolidation therapy is feasible in elderly patients with AML, and is expected to be able to further remove residual lesions and improve treatment efficacy. A large-scale clinical trial is required to confirm the effect of maintenance therapy in elderly patients with AML. PMID- 26137067 TI - Sodium glycididazole enhances the efficacy of combined iodine-125 seed implantation and chemotherapy in patients with non small-cell lung cancer. AB - The aim of the present study was to investigate the efficacy and safety of combined therapy with iodine-125 seed implantation and the gemcitabine plus cisplatin chemotherapeutic regimen, as well as treatment with the radiosensitizer sodium glycididazole (CMNa), in patients with non-small cell lung cancer (NSCLC). The 40 patients with NSCLC in the experimental group (19 females; mean age, 52.3+/-11.5 years; age range, 34-74 years) received the combined therapy and CMNa, and the 41 controls (13 females; mean age, 53.7+/-10.7 years; age range, 8 79 years) received the combined therapy only. The response rate in the experimental group was significantly higher than in the control group (85.5 vs. 63.4%; P=0.027), with no apparent complications. Therefore, it was concluded that such therapy may be reliable and well-tolerated for the treatment of patients with NSCLC. PMID- 26137068 TI - Adherence and awareness of the therapeutic intent of oral anticancer agents in an outpatient setting. AB - The aim of the present study was to clarify the adherence and awareness of oral anticancer agents by type and therapeutic purpose in outpatients prescribed with tegafur/gimeracil/oteracil potassium (S-1) or capecitabine. Outpatients undergoing treatment with the S-1 or capecitabine oral anticancer agents at Ogaki Municipal Hospital (Ogaki, Japan) in June 2013 completed a questionnaire survey and the survey findings were evaluated. No significant differences in medication adherence were identified between the patients administered S-1 and the patients administered capecitabine (P=0.4586). In addition, no significant differences were identified in therapeutic purpose between adjuvant therapy, and advanced and recurrent therapies. However, for S-1 and capecitabine, medication adherence was significantly higher in those undergoing combination therapy compared with those undergoing monotherapy (P=0.0046). In addition, for patients taking S-1, the median age for good adherence was significantly lower than that for insufficient adherence (66.1+/-10.5 vs. 72.1+/-7.9 years, respectively; P=0.0035). Furthermore, a significant negative correlation was identified between the awareness score of research regarding the medication and age (n=109; P=0.0045). In conclusion, for patients treated with S-1 or capecitabine, the type and therapeutic purpose of oral anticancer agents did not affect medication adherence. Elderly patients expressed a low interest in medications and typically exhibited insufficient medication adherence. Therefore, patient guidance by pharmacists is important, as it may result in improved medication adherence and an improved understanding of the treatment side-effects in patients self administering prescribed drugs. PMID- 26137069 TI - Survivin is not a promising serological maker for the diagnosis of hepatocellular carcinoma. AB - Survivin expression in the serum of patients with hepatocellular carcinoma (HCC) and nonmalignant chronic liver diseases remain to be elucidated. The aims of the present study were to evaluate the diagnostic role of survivin in the serum of patients with HCC and identify which ELISA kit performed best in detecting the levels of serum survivin. In total, 80 patients were included in the present study, including 20 patients with HCC, 20 patients with liver cirrhosis, 20 patients with chronic hepatitis B virus infection and 20 healthy volunteers. The levels of survivin protein in the serum were detected using two different ELISA kits (R&D and Abnova). The positive ratios of serum survivin detected by the R&D ELISA kit in all the cases were 8.75% (7/80; median, 0 pg/ml; range, 0-39.8 pg/ml) and in HCC patients were 5% (1/20; median, 0 pg/ml; range, 0-39.8 pg/ml). For the same samples analyzed using the Abnova ELISA kit, the positive ratios of serum survivin in all the cases were 22.5% (18/80; median, 0 pg/ml; range, 0 553.5 pg/ml) and in HCC patients were 25% (5/20; median, 0 pg/ml; range, 0-93.5 pg/ml). The results obtained by the different ELISA kits demonstrated no statistically significant differences in the level of survivin between HCC patients and healthy controls. The correlation coefficient was 0.0064 (P=0.481) when analyzing the same serum samples with the different ELISA kits. In addition, the highest positive ratio of serum survivin was observed using the Abnova kit. A statistically significant difference in the results was observed between the R&D and Abnova kits. In general, the levels and positive ratios of serum survivin in the patients with HCC were significantly low. Furthermore, no difference was observed between HCC patients and controls in regard to the levels of serum survivin detected by the R&D and Abnova ELISA kits. In conclusion, survivin is unlikely to be a promising serological maker for the diagnosis of HCC. PMID- 26137070 TI - Effect of thalidomide in combination with gemcitabine on human pancreatic carcinoma SW-1990 cell lines in vitro and in vivo. AB - Pancreatic cancer is one of the most frequently occurring malignancies worldwide and it is the fourth most common cause of cancer-associated mortality in Western countries. Thalidomide (THD) plays an important role in tumor therapy, as it is able to promote early stage apoptosis and inhibit the process of angiogenesis. The present study evaluated the ability of the combination of THD and gemcitabine (GEM) to inhibit the growth of the pancreatic cancer SW-1990 cell line in vitro and in vivo. Early apoptosis in the SW-1990 cells was detected by the Annexin V/propidium iodide double staining method, the level of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis. In addition, the expression of vascular endothelial growth factor in transplanted tumor tissue was measured by RT-PCR, immunohistochemistry and western blot analysis. Cluster of differentiation 34 positivity was considered to indicate the microvessel density. Subsequent to treatment with THD and GEM alone or in combination, it was found that the expression of Bax was upregulated, while the expression of Bcl-2 was downregulated, and the growth of SW-1990 cells and transplanted tumors in nude mice was evidently inhibited. The administration of THD in combination with GEM may demonstrate a potent antitumor effect that increases with increasing dose. The mechanism behind the antitumor effect may be associated with the inhibition of tumor angiogenesis and induction of the apoptosis pathway. PMID- 26137071 TI - Surgically resected human tumors reveal the biological significance of the gastric cancer stem cell markers CD44 and CD26. AB - Cancer tissue is maintained by relatively small populations of cancer stem cells (CSCs), which are involved in chemotherapy resistance, recurrence and metastasis. As tumor tissues are comprised of various cells, studies of human clinical samples are important for the characterization of CSCs. In the present study, an expression profiling study was performed in which an anti-cell surface marker antibody-based array platform, a flow cytometry-based cell separation technique and a tumorigenicity analysis in immunodeficient animals were utilized. These approaches revealed that the markers cluster of differentiation (CD)44 and CD26 facilitated the fractionation of surgically resected human gastric cancer (GC) cells into the following subset populations with distinct tumorigenic potentials: Highly tumorigenic CD26+CD44+ cells (6/6 mice formed tumors), moderately tumorigenic CD26+CD44- cells (5/6 mice formed tumors), and weakly or non tumorigenic CD26-CD44- cells (2/6 mice formed tumors). Furthermore, exposure to 5 fluorouracil significantly increased the proportion of CD26+ cells in vitro. The present study demonstrated that the combined expression of CD26 and CD44 presents a potential marker of human GC stem cells. PMID- 26137072 TI - First adult case of sporadic localized glomerulocystic kidney mimicking a tumor. AB - Glomerulocystic kidneys (GCKs) are mainly observed in infants and young children, and are characterized by the cystic dilatation of Bowman's space to form glomerular cysts (GCs). GCKs are associated with various conditions. Additionally, the cystogenesis of GCKs remains controversial. The present study describes a rare adult case of a sporadic localized GCK that radiologically mimicked a multilocular cystic tumor, and analyses the features of GC. A 42-year old male with hematuria underwent a right partial nephrectomy for a cystic mass. The majority of the cyst was distributed in the cortex and contained a single collapsed glomerulus. Using serial sections, narrow and serpiginous proximal tubules that continued to the GCs were detected. These findings suggested that obliteration at the glomerulotubular junction was not the primary cause of GC in this case. To the best of our knowledge, this is the first adult case of a sporadic localized GCK mimicking a tumor. Unnecessary surgical procedures may be avoided by careful evaluation of computed tomography scans and magnetic resonance imaging, although localized GCKs are quite rare. PMID- 26137073 TI - Treatment decision-making for sporadic small vestibular schwannoma in a pediatric patient: A case report and literature review. AB - The current study reports the case of a 15-year-old male who presented with hearing loss due to a small left-sided vestibular schwannoma (VS) not associated with neurofibromatosis type 2 (NF2), which had been apparent for six months. Magnetic resonance imaging with gadolinium diethylenetriamine penta-acetic acid revealed a mass, 10 mm in diameter, located in the left inner auditory canal. The patient had no family history of NF2 and gene mutation analysis showed no signs of the condition. Small sporadic or non-NF2 VS is extremely rare and the treatment decision-making process is complicated in children when considering the implications for the impairment of childhood development and lifelong disability. Following careful consideration, the patient in the present study underwent treatment with stereotactic radiosurgery. The five-year post-operative follow-up examination showed tumor stability without additional neurological deficits and at the time of writing the patient was alive and well. PMID- 26137074 TI - Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay. AB - Ovarian cancer has a poor prognosis, primarily due to the heterogeneity in chemosensitivity among patients. In the present study, this heterogeneity was evaluated in ovarian epithelial cancer (OEC) using an in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA). Specimens were collected from 80 patients who underwent cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissues were tested for sensitivity to paclitaxel (PTX), carboplatin (CBP), topotecan (TPT), gemcitabine (GEM), docetaxel (TXT), etoposide, bleomycin and 4-hydroperoxycyclophosphamide using ATP-TCA. The sensitivity, specificity, positive predictive value and negative predictive value for the clinical chemotherapy sensitivity of OEC were 88.6, 77.8, 83 and 84.8%, respectively. PTX demonstrated the highest sensitivity of all agents tested (82.5% in all specimens, 85.7% in recurrent specimens), followed by CBP (58.8 and 60.7%, respectively). The sensitivities to PTX and docetaxel (P<0.001) were correlated, in addition to those of CBP, TPT and GEM (P<0.001). Early-stage (I/II) and high- to mildly-differentiated OEC specimens revealed a lower chemosensitivity than advanced-stage (III) or low-differentiated specimens, respectively. The present study indicated that ATP-TCA is an effective method for guiding the choice of chemotherapy drugs. Notable heterogeneity of chemosensitivity was observed in the OEC specimens. PMID- 26137075 TI - Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis. AB - The hedgehog (Hh) signaling pathway is vital to vertebrate development, the homeostatic process and tumorigenesis. Epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells become mesenchymal-appearing cells, which in turn promotes cancer metastasis and invasion. Resveratrol is a natural polyphenolic compound found in grapes, a variety of berries, peanuts and other plants. Numerous studies have demonstrated that the Hh signaling pathway is able to regulate the EMT, and that resveratrol can suppress carcinoma invasion and metastasis. In addition, certain studies have indicated that resveratrol can inhibit the Hh signaling pathway and EMT in cancers other than gastric cancer. The purpose of the present study was to investigate the inhibitory effect of resveratrol on the Hh signaling pathway and EMT in gastric cancer in vitro. Gastric cancer SGC-7901 cells were treated with resveratrol or cyclopamine at different concentrations. The viability of the cells was assessed using an MTT assay. The expression of Gli-1, a key component of the Hh signaling pathway, and Snail, E-cadherin and N-cadherin, key components of EMT, was detected by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The invasion and metastasis of the cells were observed by performing a cell scratch test. The RT-PCR and western blotting showed a decrease in Gli-1, Snail and N cadherin expression, and an increase in E-cadherin expression in the resveratrol and cyclopamine group compared with the control group, suggesting that resveratrol inhibited the Hh pathway and EMT, as did cyclopamine. The MTT assay indicated that the viability of the SGC-7901 cells was significantly decreased in a concentration-dependent manner following resveratrol and cyclopamine treatment. The cell scratch test showed slower cell invasion and metastasis in the resveratrol and cyclopamine groups. These findings indicated that resveratrol was able to inhibit the Hh signaling pathway and EMT, and suppress invasion and metastasis in gastric cancer in vitro. PMID- 26137076 TI - High performance liquid chromatography: Tandem mass spectrometric determination of cisplatin levels in different visceral pleura layers of rats. AB - The aim of the present study was to investigate the concentration of cisplatin in different layers of the visceral pleura in rats, following drug administration. In this study, a sensitive and specific liquid chromatography method coupled with electrospray ionization-tandem mass spectrometry was established to investigate the disposition of cisplatin in different layers of the visceral pleura in rats. Methodological data, including specificity, linearity, accuracy, recovery, precision and lower limits of quantification, confirmed that this novel method may be used to efficiently quantify the cisplatin concentrations in visceral pleura of rats following administration of the drug. Furthermore, the results demonstrated that the desired drug concentration was not achieved in the outer or inner elastic layers of the visceral pleura following injection with cisplatin through various administration methods. PMID- 26137077 TI - 3,3'-diindolylmethane potentiates tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis of gastric cancer cells. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically kills cancer cells without destroying the majority of healthy cells. However, numerous types of cancer cell, including gastric cancer cells, tend to be resistant to TRAIL. The bioactive product 3,3'-diindolylmethane (DIM), which is derived from cruciferous vegetables, is also currently recognized as a candidate anticancer agent. In the present study, a Cell Counting Kit 8 cell growth assay and an Annexin V-fluorescein isothiocyanate apoptosis assay were performed to investigate the potentiating effect of DIM on TRAIL-induced apoptosis in gastric cancer cells, and the possible mechanisms of this potentiation. The results obtained demonstrated that, compared with TRAIL or DIM treatment alone, co treatment with TRAIL (25 or 50 ng/ml) and DIM (10 umol/l) induced cytotoxic and apoptotic effects in BGC-823 and SGC-7901 gastric cancer cells. Furthermore, western blot analysis revealed that the protein expression levels of death receptor 5 (DR5), CCAAT/enhancer binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were upregulated in the co-treated gastric cancer cells. To the best of our knowledge, the present study is the first to provide evidence that DIM sensitizes TRAIL-induced inhibition of proliferation and apoptosis in gastric cancer cells, accompanied by the upregulated expression of DR5, CHOP and GRP78 proteins, which may be involved in endoplasmic reticulum stress mechanisms. PMID- 26137078 TI - Unusual complication of multiple splenic abscesses arising from a feeding jejunostomy tube subsequent to total gastrectomy: A case report and literature review. AB - Splenic abscess is a rare clinical entity. The present study reports a case of a patient that suffered from splenic abscess secondary to septicemia resulting from Klebsiella pneumoniae infection following the removal of the feeding jejunostomy tube that was utilized subsequent to the patient undergoing total gastrectomy as part of the treatment regimen for gastric adenocarcinoma. The early clinical presentation was nonspecific and multiple splenic abscesses were subsequently identified. To reduce the risks of an additional surgical procedure in this particular patient, laparoscopic assisted splenotomy and catheter drainage were performed. Due to the severe complications that occurred in the present patient, no adjuvant chemotherapy was administered. Therefore, the unusual complication of splenic abscess subsequent to total gastrectomy should be noted, and the routine feeding jejunostomy tube placement at the time of total gastrectomy should be discussed and re-assessed. PMID- 26137079 TI - Carcinoid tumor of the appendix: A case report. AB - Carcinoid tumors are the most common neoplasm of the appendix. The clinical presentation of these lesions is often similar to that of acute appendicitis, or the tumors are asymptomatic. The carcinoids are commonly found incidentally during histopathological examination of the resected appendix following appendectomy or other abdominal procedures. Appendiceal carcinoids usually behave as benign tumors and appendicectomy alone is a sufficient treatment in the majority of cases, while for larger lesions, right colectomy should be performed. The prognosis of patients with local appendiceal carcinoids is excellent. The present study reports the case of a 22-year-old female patient that presented with recurrent right lower abdominal pain of a three-year duration. The patient underwent successful appendectomy and recovered four days later. Subsequently, an appendiceal carcinoid tumor located at the tip of the appendix was diagnosed by histopathological examination. Follow-up examination one year after surgery revealed that the patient was well with no discomfort. PMID- 26137080 TI - Radiation therapy as part of the therapeutic regimen for extensive multilocular myxedema in a patient with exophthalmos, myxedema and osteoarthropathy syndrome: A case report. AB - Exophthalmos, myxedema and osteoarthropathy (EMO) comprise the triad known as EMO syndrome, which is rarely observed in patients with autoimmune thyroid disease. The present study reports the case of a patient with EMO, including the response of this rare combination to radiotherapy. A 48-year-old patient with EMO syndrome presented to the Department of Radiation Oncology, University Hospital of Muenster, eight years prior to writing with therapy-resistant pretibial myxedema and hypertrophic osteoarthropathy of the metacarpal bones. The patient had been diagnosed with Graves' disease (GD) 26 years prior to presentation, which was treated by thyroidectomy and radioiodine therapy. Four years subsequent to the diagnosis of GD, the patient developed exophthalmos, which was treated using radiotherapy. An evident pretibial, foot and hand myxedema developed within the 10 years following the onset of orbitopathy. The skin lesions were treated using radiation therapy subsequent to the failure of multiple surgical procedures and medical treatments. Almost eight years subsequent to the administration of irradiation, no recurrence was observed on the lower right leg, nor was any recurrence on the lower left leg observed approximately four years subsequent to the completion of radiotherapy. However, an additional lesion on the left hand demonstrated slow progression following treatment with radiation therapy. The present study indicates that radiation therapy can be considered as adjuvant therapy for patients with refractory myxedema, to prevent or delay the recurrence of myxedema subsequent to surgical excision. PMID- 26137081 TI - Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer. AB - Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. In advanced and metastatic GC, conventional chemotherapy results in limited efficacy and the average survival rate is currently approximately 10 months. Dysregulated activation of numerous genes, including zinc finger, DHHC type containing 14; caspase-associated recruitment domain-containing protein; and Ras association domain family member 10, have been implicated in GC. The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer. However, the mechanism of the tumor suppressor function of LTF in GC remains unclear. In the present study, the expression levels of LTF in patient GC tissue samples were investigated using reverse transcription-quantitative polymerase chain reaction, and it was demonstrated that the LTF mRNA expression level in GC tissue samples was reduced by ~20-fold compared with the adjacent non-cancerous tissues (t=4.56, P<0.01). A similar trend in LTF protein expression was observed by western blot analysis. Furthermore, the present study demonstrated that the mitogen-activated protein kinase (MAPK) signaling pathway intermediates p38, c Jun N-terminal kinase (JNK) and c-Jun were highly expressed in GC tissue samples, and indicated that LTF downregulation may be associated with the dysregulation of the MAPK signaling pathway in GC tissues. In addition, the present study indicated that LTF overexpression reduced the expression of p38, JNK2 and c-Jun in the GC cell line, SGC7901. The present study demonstrates that LTF expression is downregulated in GC tissues and that LTF may serve an important role in the dysregulation of the MAPK signaling pathway. PMID- 26137082 TI - Expression and clinical significance of vascular endothelial growth factor and fms-related tyrosine kinase 1 in colorectal cancer. AB - The aim of the present study was to investigate the prognostic value of vascular endothelial growth factor (VEGF) and its receptor, fms-related tyrosine kinase-1 (FLT-1), in patients with colorectal cancer. An immunohistochemical approach was used to detect the protein expression of VEGF and FLT-1 in 90 patients with colorectal cancer. The impact of VEGF and FLT-1 tumor cell expression, in addition to other factors, on overall survival (OS) was retrospectively assessed in 90 patients. Multivariate analysis was performed in order to determine the prognostic significance of the factors. The positive expression rate of VEGF in the colorectal cancer tissues was 62.2% (56/90). The positive expression rate of FLT-1 in colorectal cancer tissues was 48.9% (44/90). The results of the log-rank test revealed that improved OS rates were significantly associated with the absence of VEGF expression (P<0.0001). By contrast, FLT-1 expression had no significant impact on OS (P=0.289). Upon multivariate analysis, VEGF expression (P=0.038) and clinical stage (P=0.021) maintained significance. VEGF expression proved to be an independent negative predictor of OS in patients with colorectal cancer. Conversely, FLT-1 expression demonstrated no impact on OS. PMID- 26137083 TI - Re-administration of gefitinib following diffuse interstitial lung disease in a patient with advanced lung adenocarcinoma: A case report and review of the literature. AB - Interstitial lung disease (ILD) is a severe adverse effect of gefitinib treatment. Re-administration of gefitinib to patients suspected of suffering from gefitinib-induced ILD requires cautious consideration. In the majority of cases, gefitinib is not re-administered to such patients. The present study reports a case of advanced lung adenocarcinoma, where the patient developed gefitinib induced ILD and gefitinib was re-administered at 3.5 months after discontinuation of gefitinib treatment. Initially, the patient achieved partial clinical remission, but developed diffuse ILD following gefitinib administration for 5 months. Following the onset of ILD, gefitinib was discontinued immediately and low-dose corticosteroids were administered at the early stages of ILD. Subsequent to recovery from the lung injury, gefitinib was re-administered along with N acetylcysteine. The patient presented with good lung adenocarcinoma control and did not experience a recurrence of ILD for >16 months. Thus, early discontinuation and gefitinib re-administration with N-acetylcysteine may be a potential novel treatment strategy for gefitinib-induced ILD. PMID- 26137084 TI - Radiotherapy treatment of large esophageal leiomyosarcoma: A case report. AB - Leiomyosarcoma of the esophagus is a rare type of tumor, characterized by a malignant phenotype and smooth muscle histology. Previously, barium studies have been used to identify areas of luminal narrowing, expansile intraluminal masses or large intramural masses with ulceration or tracking. Furthermore, endoscopic biopsies appear to be associated with a high false negative rate, particularly in cases where the mucosa is intact. The optimal treatment strategy is surgical resection, while the role of adjuvant radiotherapy and chemotherapy is controversial. In addition, the prognosis of patients with leiomyosarcoma of the esophagus is improved compared with patients suffering from squamous esophageal cancer. The present study described the case of a 48-year-old woman who presented with dysphagia and was diagnosed with a large leiomyosarcoma of the esophagus. The patient was successfully treated with radiotherapy and remains disease-free two years after the completion of treatment. In addition, the present study conducted a review of the relevant literature, reporting previous cases of esophageal leiomyosarcoma and potential strategies for the management of this disease. PMID- 26137085 TI - XRCC3 T241M polymorphism and melanoma skin cancer risk: A meta-analysis. AB - Although the T241M polymorphism in the X-ray cross-complementing group 3 (XRCC3) gene has been implicated in the pathogenesis of melanoma, the results have been inconsistent. In this study, a meta-analysis was performed to assess the association of XRCC3 T241M polymorphism with melanoma. Published literature from PubMed and Embase databases was retrieved. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects models. A total of six case-control studies containing 2,133 patients and 3,141 controls were enrolled into this meta-analysis. In a combined analysis, the results revealed no significant association between XRCC3 T241M polymorphism and melanoma risk in the overall population. In the subgroup analysis by ethnicity, no significant associations between the XRCC3 T241M polymorphism and melanoma risk were identified in Caucasians. However, when the analyses were restricted to three larger studies (n>500 cases), a significant association was noted with melanoma (TT vs. MT: OR=1.20, 95% CI=1.04-1.38; dominant model: OR=0.86, 95% CI=0.75-0.98). In conclusion, the meta-analysis results suggest that the XRCC3 T241M polymorphism was associated with risk of melanoma. Further large and well designed studies are needed to confirm this conclusion. PMID- 26137086 TI - Nipple-sparing mastectomy in breast cancer patients: The role of adjuvant radiotherapy (Review). AB - The present study aimed to evaluate the role of adjuvant radiotherapy (RT) following nipple-sparing mastectomy (NSM) for patients with ductal carcinoma in situ and invasive breast cancer, based on the published literature. Currently, there is no standard for RT following NSM. NSM aims to spare the nipple areola complex (NAC) without compromising locoregional control. Long-term follow-up studies have begun to show promising results. A search of the English literature was performed using the Medline database and Cochrane central library, with the keywords 'nipple/areola-sparing mastectomy', 'whole skin mastectomy' and 'NAC preservation'. A total of 32 original studies with data on NSM in terms of locoregional control, NAC control, NAC necrosis and adjuvant RT were identified. The median locoregional and NAC recurrence rates were 3.2 and 1.4% (range, 0 28.4% and 0-3.7%), respectively. The volume of remaining breast tissue following NSM was reported inconsistently. In 15 studies, RT was not mentioned. In the remaining 17 studies, RT was administered in 0-100% of patients. Only 7 studies provided detailed information regarding the use of adjuvant RT. Adjuvant thoracic wall irradiation was not used in certain studies, not even for locoregionally advanced tumors. Overall, NSM appears a feasible treatment without increased risk of locoregional recurrence for selected patients. The role of adjuvant RT following NSM requires further clarification. The decision regarding adjuvant RT must be made in interdisciplinary tumor boards and with consideration of the individual situation of the patient. PMID- 26137087 TI - Brain perfusion and permeability in patients with advanced, refractory glioblastoma treated with lomustine and the transforming growth factor-beta receptor I kinase inhibitor LY2157299 monohydrate. AB - Transforming growth factor-beta (TGF-beta) signaling is associated with tumor progression and vascularization in malignant glioma. In the present study, magnetic resonance imaging was used to evaluate changes in the size and vascularity of glioblastomas in 12 patients who were treated with lomustine and the novel inhibitor of TGF-beta signaling, LY2157299 monohydrate. A response in tumor size was observed in 2 of the 12 patients; in 1 of these 2 patients, a reduction in vascular permeability and perfusion was also detected. The effect was observed following 4 cycles of treatment (~3 months). Changes in vascularity have not previously been attributed to treatment with lomustine; therefore, the effect may be associated with LY2157299 treatment. LY2157299 does not appear to have an anti-angiogenic effect when combined with lomustine, and hence may have a different mechanism of action profile compared with anti-angiogenic drugs. PMID- 26137088 TI - Artesunate-enhanced apoptosis of human high-risk myelodysplastic cells induced by the DNA methyltransferase inhibitor decitabine. AB - The present study aimed to investigate whether artesunate (ART) could enhance the rate of apoptosis induced by decitabine (DAC) in the high-risk myelodysplastic syndrome (MDS) SKM-1 cell line, and examine the potential underlying mechanisms. The cytotoxicity and effect upon the apoptosis of ART and DAC in the SKM-1 cells was detected using the cell counting kit-8 assay and flow cytometry, respectively. The SKM-1 protein expression levels of activated caspase-3, -9 and 8, cleaved poly(ADP-ribose) polymerase and apoptosis-inducing factor (AIF) were measured by western blotting. The laser confocal microscope analysis revealed AIF transfer to the nucleus. The growth inhibition and apoptosis rates of the ART- and DAC-treated SKM-1 cells were significantly increased compared with those of the single agent-treated SKM-1 cells (P<0.05). In addition, ART and DAC induced caspase-dependent apoptosis, while ART, but not DAC, induced caspase-independent apoptosis via AIF transfer from the mitochondria to the nucleus. In addition, ART DAC-induced cell death was not attenuated by the caspase-3/7 inhibitor, Ac-DEVD CHO. The results of the present study suggested that the ART-DAC combination exhibited increased effectiveness compared with the single-agent therapy, in vitro. The ART-DAC combined therapy not only activated a caspase-dependent apoptotic pathway, but also a caspase-independent mitochondrial pathway. PMID- 26137089 TI - RUNX2 RNA interference inhibits the invasion of osteosarcoma. AB - It has previously been demonstrated that the expression of the RUNX2 gene is increased in osteosarcoma tissues or cell lines; however, there is little research available on the effect of RUNX2 on osteosarcoma invasion. In the present study, small interfering (si)RNA to RUNX2 was designed and synthesized, and then transfected into SAOS-2 cells. The effects of RUNX2 RNA interference on the invasion of osteosarcoma cells were detected by the soft agar colony forming test and Transwell(r) chamber assay. The expression of the associated proteins, vascular endothelial growth factor (VEGF), matrix metalloprotein-2 (MMP-2) and MMP-9, was detected by western blot analysis. The results revealed that the number of cell colonies was reduced dose-dependently by the siRNA and that the number of cells permeating through the filter membrane was decreased following transfection with the siRNA. The inhibition of RUNX2 caused a notable decrease in VEGF, MMP-2 and MMP-9 expression (0.16+/-0.04, 0.16+/-0.02 and 0.12+/-0.02) compared with the empty vector (0.86+/-0.22, 0.74+/-0.16 and 0.81+/-0.16) and blank control (0.78+/-0.12, 0.82+/-0.18 and 0.78+/-0.14) groups, respectively (P<0.01). It can therefore be concluded that RUNX2 siRNA inhibits the invasion of osteosarcoma cells by inhibiting the expression of VEGF, MMP-2 and MMP-9. PMID- 26137090 TI - Acute myeloid leukemia with monosomy 7, ectopic virus integration site-1 overexpression and central diabetes insipidus: A case report. AB - Central diabetes insipidus (DI) is a rare complication in patients with acute myeloid leukemia (AML), typically occurring in patients with abnormalities of chromosomes 3 or 7. The association between AML with monosomy 7 and DI has been described in a number of studies; however, DI has been rarely reported in cases of ectopic virus integration site-1 (EVI1)-positive AML with monosomy 7. The current study reports a case of AML with monosomy 7 and EVI1 overexpression, with central DI as the initial symptom. The patient was an 18-year-old female who presented with polyuria and polydipsia. Bone marrow aspiration revealed 83.5% myeloperoxidase-positive blasts without trilineage myelodysplasia. The karyotype was 45,XX,-7, and the patient presented monosomy 7 and EVI1 overexpression ( 7/EVI1+) without 3q aberration. Treatment with induction therapy was unsuccessful. To the best of our knowledge, this is the second case of DI-AML with -7/EVI1+ and without a 3q aberration. The possible mechanisms associated with EVI1, monosomy 7 and DI were investigated. PMID- 26137091 TI - Expression changes of cell-cell adhesion-related genes in colorectal tumors. AB - Epithelial tissues achieve a highly organized structure due to cell-cell junction complexes. Carcinogenesis is accompanied by changes in cell interactions and tissue morphology, which appear in the early stages of benign tumors and progress along with invasive potential. The aim of the present study was to analyze the changes in expression levels of genes encoding intercellular junction proteins that have been previously identified to be differentially expressed in colorectal tumors compared with normal mucosa samples (fold change, >2.5) in genome-wide expression profiling. The expression of 20 selected genes was assessed using quantitative reverse transcription polymerase chain reaction in 26 colorectal cancer, 42 adenoma and 24 normal mucosa samples. Between these tissue types, differences were observed in the mRNA levels of genes encoding adherens junction proteins (upregulation of CDH3 and CDH11, and downregulation of CDH19 and PTPRF), tight junction proteins (upregulation of CLDN1 and CLDN2, and downregulation of CLDN5, CLDN8, CLDN23, CLDN15, JAM2 and CGN) and desmosomes (upregulation of DSC3 and DSG3, and downregulation of DSC2), in addition to a decrease in the expression of certain other genes involved in intercellular connections: PCDHB14, PCDH7, MUPCDH and NEO1. The differences between tissue types were statistically significant, and separate clustering of normal adenoma and carcinoma samples was observed in a hierarchical clustering analysis. These results indicate that the morphological changes in neoplastic colon tissue that occur during the 'adenoma carcinoma sequence' are accompanied by specific changes in the expression of multiple genes encoding the majority of cell-cell junction complexes. The particular differential expression patterns appear to be consistent among patients with cancer and adenoma, in addition to normal mucosa samples. PMID- 26137092 TI - Rana catesbeiana ribonuclease induces cell apoptosis via the caspase-9/-3 signaling pathway in human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines. AB - Human glioblastoma multiforme is one of the most aggressive malignant brain tumor types, and the mean survival time of patients with a brain tumor is <2 years when traditional therapies are administered. Thus, numerous studies have focused on the development of novel treatments for brain tumors. Frog ribonucleases, such as Onconase and Rana catesbeiana ribonuclease (RC-RNase), exert antitumor effects on various tumor cells, including cervical cancer, breast cancer, hepatoma, leukemia, pancreatic cancer and prostate cancer cells. In addition, frog Onconase has been applied as a treatment in clinical trials. However, the antitumor effects of frog ribonucleases on brain tumors are unclear. Previous studies have indicated that RC-RNase demonstrates a decreased cytotoxic effect in normal cells compared with Onconase. Therefore, the present study investigated the ability of RC-RNase to exert antitumor activities on human glioblastoma. It was found that RC-RNase inhibits the growth of the human glioblastoma DBTRG, GBM8901 and GBM8401 cells. In addition, the present study revealed that RC-RNase induces caspase-9/-3 activity and triggers the apoptotic cell death pathway in human glioblastoma cells. Notably, it was also demonstrated that RC-RNase effectively inhibits the growth of human glioblastoma tumors in a nude mouse model. Overall, the present study indicates that RC-RNase may be a potential agent for the treatment of human glioblastoma. PMID- 26137093 TI - Resection of a laryngeal hemangioma in an adult using an ultrasonic scalpel: A case report. AB - Adult laryngeal hemangioma is an extremely rare and slowly progressing vascular tumor. The present study describes the first reported case of a male with a large laryngeal hemangioma that was treated by ultrasonic scalpel. A 61-year-old male presented to our hospital with a recurrent pharyngeal foreign body sensation, without hoarseness, hemoptysis, expectoration or dyspnea. A blue-black mass was detected in the right pyriform sinus, with a morular surface and a wide pedicle positioned lateral to the right arytenoid cartilage and aryepiglottic fold under electronic laryngoscopy. Following tracheotomy under local anesthesia, right superior laryngeal artery ligation and laryngeal hemangioma resection via a lateral neck hypopharyngeal approach were performed under general anesthesia using an ultrasonic scalpel. Pathological examination verified that the tumor was a cavernous hemangioma. On day 11, subsequent to post-operative anti-inflammatory and symptomatic treatment, electronic laryngoscopy showed that the arytenoid mucosal edema had decreased and that the movement of the arytenoid was good. There was no recurrence of hemangioma during a 2-year follow-up period. Therefore, it is recommended that complete surgical resection using an ultrasonic scalpel should be considered for similar cases involving large laryngeal hemangiomas. PMID- 26137094 TI - Uterine leiomyoma mimicking a gastrointestinal stromal tumor with chronic spontaneous hemorrhage: A case report. AB - Uterine leiomyomas are the most common tumors to affect women. Cases of uterine leiomyoma mimicking a gastrointestinal stromal tumor with chronic spontaneous hemorrhage are extremely rare, and similar cases to that of the present study are yet to be reported. In the current study, a 48-year-old female presented with symptoms of lower abdominal pain after menses that had persisted for 4 months. The patient was initially diagnosed with uterine leiomyoma. However, according to the results of the gross and auxiliary examinations, a diagnosis of a gastrointestinal stromal tumor could not be excluded. Therefore, the patient underwent a rectal sigmoid bowel resection, subtotal hysterectomy and bilateral salpingectomy. Subsequent to surgery, the immunohistochemical examinations confirmed the initial diagnosis of uterine leiomyoma. The surgery had therefore involved an unnecessary organ resection. PMID- 26137095 TI - Ecto-5'-nucleotidase expression is associated with the progression of renal cell carcinoma. AB - Renal cell carcinoma (RCC) is a common tissue tumor that occurs across all age groups and has become one of the types of cancer with the fastest increasing incidence. Due to the resistance of RCC chemo- and radiotherapy, surgery is the only currently effective treatment. Therefore, specific markers for the diagnosis and prognosis of RCC are expected to result in novel methods of treatment. Ecto 5'-nucleotidase, also termed cluster of differentiation (CD)73, is a protein that is activated in several types of aggressive cancer and may promote cancer progression. CD73 was examined in the present study to determine the association between the protein and RCC. The expression levels of CD73 in 159 RCC tissue sections and 30 paratumorous normal renal tissue samples obtained from 235 patients that underwent nephrectomy were examined by immunohistochemical staining. By contrast, the expression level of P-glycoprotein (P-gp), a potential prognostic factor in RCC, was also examined in 85 RCC and 13 normal tissue samples. Intense CD73 expression was identified in 75 out of 159 RCC cell membranes compared with normal renal tissues. In contrast, there was high P-gp expression in the blood vessels of 42 out of 85 RCC tissues and there was no significant difference between the P-gp expression identified in RCC cells (34 out of 85) and the cell membrane of normal renal cells (2 out of 13). The expression level of CD73 in RCC cells was significantly associated with tumor type, tumor node metastasis (TNM) stage, and tumor grade. However, the expression of P-gp in RCC cells was only associated with the TNM stage and tumor grade. Using a multivariable Cox regression analysis, it was found that the median survival rate of RCC patients with intense CD73 expression in RCC cells was 62.06+/-5.35 months, which was drastically shorter compared with rare CD73 expression (103.72+/-3.67 months). In conclusion, the expression level of CD73 is significantly associated with RCC tumor progression and may serve as a favorable marker for the diagnosis and prognosis of RCC, in addition to being a therapeutic target for the treatment of RCC. PMID- 26137096 TI - Portal vein tumor thrombus in advanced hepatocellular carcinoma: A case report. AB - Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) is a common entity. However, the prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is extremely poor. The current study reports a case of HCC with PVTT, including a description of the gross surgical pathology and discussion of the relevance of assessing the growth of the tumor thrombus to the outcome of this disease. This case suggests that destruction of the primary tumor and PVTT must be considered according to the growth characteristics and modality of PVTT. It also indicates that transcatheter arterial embolization may be a suitable strategy for palliative treatment of patients with advanced HCC with PVTT. PMID- 26137097 TI - DNA methyltransferase 3b silencing affects locus-specific DNA methylation and inhibits proliferation, migration and invasion in human hepatocellular carcinoma SMMC-7721 and BEL-7402 cells. AB - DNA methylation is an important regulator of gene transcription, and its role in carcinogenesis has been a topic of considerable interest in previous years. The present study examined the influence of DNA methyltransferase 3b (DNMT3b) on cell proliferation, migration and invasion, and the methylation status of identified tumor suppressor genes in hepatoma SMMC-7721 and BEL-7402 cells. DNMT3b was silenced by small interfering RNA (siRNA) in human hepatocellular carcinoma cell lines. Transfection efficiency was verified using a fluorescent imaging system, reverse transcription polymerase chain reaction (RT-PCR) and western blotting. A cell proliferation assay was performed to evaluate cell viability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The migratory and invasive ability of cells was measured using a Transwell assay. Methylation specific PCR (MSP) was performed to assess methylation in the promoter region of genes. The present data revealed that DNMT3b siRNA successfully inhibited expression of the DNMT3b gene in these two liver cancer cell lines and therefore inhibited the proliferation of the transfected cells, stimulated apoptosis in the cells, led to an accumulation of cells in the G2/M phase and decreased cell migration and invasion. It was also found that silencing DNMT3b expression results in hypomethylation of specific sets of gene promoters and increases the expression of distinct set of genes in HCC cell lines. The present study is therefore useful for assessing the specificity of emerging action based on the altered expression of associated regulatory genes, particularly in methylation silenced genes. PMID- 26137098 TI - Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development. AB - Neuroblastoma is the one of the most common extracranial childhood malignancies, accounting for ~15% of tumor-associated deaths in children. It is generally considered that neuroblastoma originates from neural crest cells in the paravertebral sympathetic ganglia and the adrenal medulla. However, the mechanism by which neuroblastoma arises during sympathetic neurogenesis and the cellular mechanism that drives neuroblastoma development remains unclear. The present study investigated the cell components during neuroblastoma development in the tyrosine hydroxylase-v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (TH-MYCN) mouse model, a transgenic mouse model of human neuroblastoma. The present study demonstrates that paired-like homeobox 2b (Phox2B)+ neuronal progenitors are the major cellular population in hyperplastic lesions and primary tumors. In addition, Phox2B+ neuronal progenitors in hyperplastic lesions or primary tumors were observed to be in an actively proliferative and undifferentiated state. The current study also demonstrated that high expression levels of Phox2B promotes neuroblastoma cell proliferation and xenograft tumor growth. These findings indicate that the proliferation of undifferentiated Phox2B+ neuronal progenitors is a cellular mechanism that promotes neuroblastoma development and indicates that Phox2B is a critical regulator in neuroblastoma pathogenesis. PMID- 26137099 TI - Small hairpin RNA-mediated Kruppel-like factor 8 gene knockdown inhibits invasion of nasopharyngeal carcinoma. AB - The present study aimed to characterize the expression of Kruppel-like factor 8 (KLF8) in nasopahryngeal carcinoma (NPC) cell lines and determine its effect on tumor development and invasion following KLF8 gene knockdown by small hairpin RNA (shRNA). KLF8 expression in four NPC cell lines was examined by quantitative polymerase chain reaction (qPCR) and western blotting. KLF8 was knocked down in the SUNE1-5-8F/Sh-KLF8 cell line using shRNA, and the resulting stable cell line SUNE1-5-8F-sh-KLF8 was transplanted into nude mice in order to observe tumor formation and invasion. The results obtained from qPCR and western blotting revealed that, of the four NPC cell lines, KLF8 expression was lowest in the CNE 1 cells and highest in the SUNE1-5-8F cells. The tumor xenograft mouse models revealed that SUNE1-5-8F/Sh-KLF8 cells had a reduced ability for tumor formation and invasion compared with the control group. These results demonstrated for the first time that KLF8 modulates the formation and invasive ability of nasopharyngeal carcinoma. PMID- 26137100 TI - Modified simultaneous integrated boost radiotherapy for large retroperitoneal malignant tumor: A case report. AB - The current study reports the case of a large retroperitoneal tumor treated with modified simultaneous integrated boost (SIB) radiotherapy. A 45-year-old female presented to the emergency department complaining of left abdominal pain and fever. A computed tomography scan detected a retroperitoneal tumor of 12*16*16 cm, and a biopsy revealed a poorly-differentiated adenocarcinoma. The patient was diagnosed with a large adenocarcinoma originating from the left ureter, with no distant metastasis. Due to the patient's poor physical condition, surgery was not recommended, and the patient was referred to the Department of Radiation Oncology (Yamagata University Hospital, Yamagata, Japan). Modified SIB radiotherapy was administered following the acquisition of written consent from the patient. The total irradiation dose to the center of the tumor and to the surrounding healthy tissue was ~96 Gy/33 fractions and <60 Gy/33 fractions, respectively. At the end of the radiotherapeutic course, the tumor volume was reduced by >=80%, and the residual tumor was surgically resected. As a result of the resection, a complete pathological response was confirmed; the patient has been recurrence-free for >3 years with no complications. Modified SIB radiotherapy may be safely administered, with favorable outcomes. Complete recovery can be achieved with this technique, even in a patient with a large radioresistant tumor. PMID- 26137101 TI - Eukaryotic translation initiation factor 3, subunit C is overexpressed and promotes cell proliferation in human glioma U-87 MG cells. AB - Disrupted protein translation is prevalent in tumours. Eukaryotic translation initiation factors (eIFs) were found to play an important role in various tumours. However, the involvement of eIFs in glioma remains to be elucidated. The present study explored the expression and the role of eIF 3, subunit C (eIF3c) in human glioma. The expression of eIF3c in glioma tissues was evaluated by immunohistochemistry. The impact of eIF3c inhibition on U-87 MG was explored in vitro and in vivo by lentivirus-mediated siRNA targeting eIF3c. The results revealed that overexpression of eIF3c was present in glioma tissues. Knockdown of eIF3c significantly impaired cell proliferation and colony formation, further induced cell cycle arrest and apoptosis in the U-87 MG cell line. Furthermore, tumoursphere formation in the U-87 MG glioma xenograft model was blocked by eIF3c knockdown. The involvement of eIF3c in the tumorigenesis of glioma was confirmed, suggesting eIF3c may be a promising therapy target in human glioma. PMID- 26137102 TI - Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells. AB - The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells. PMID- 26137103 TI - Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells. AB - Cordycepin, also termed 3'-deoxyadenosine, is a derivative of the nucleoside adenosine that represents a potential novel class of anticancer drugs targeting the 3' untranslated region of RNAs. Cordycepin has been reported to induce apoptosis in certain cancer cell lines, but the effects of cordycepin on human neuroblastoma cells have not been studied. In the present study, an MTT assay revealed that cordycepin inhibits the viability of neuroblastoma SK-N-SH and BE(2)-M17 cells in a dose-dependent manner. In addition, cordycepin increases the early-apoptotic cell population of SK-N-SH cells, as determined by fluorescence activated cell sorting analysis. The induction of apoptosis in neuroblastoma cells by cordycepin was further confirmed by western blotting, which revealed cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase 1 in the SK-N-SH and BE(2)-M17 cells. Cordycepin also induced the formation of a punctate pattern of light-chain 3 (LC3)-associated green fluorescence in the SK-N-SH cells transfected with a pEGFP-LC3 vector. Furthermore, western blotting revealed cleavage of LC3 A/B in cordycepin-treated neuroblastoma SK-N-SH cells. Taken together, the results indicate that cordycepin significantly increases apoptosis and autophagy in neuroblastoma cells, and may therefore be a drug candidate for neuroblastoma therapy, but requires additional evaluation. PMID- 26137104 TI - Inflammatory myofibroblastic tumor of the hand: A case report. AB - The present study reports the case of a 58-year-old male patient who repeatedly presented with hand ulcers that were diagnosed as cellulitis. Upon histological analysis, however, an inflammatory myofibroblastic tumor (IMT) was diagnosed. IMTs rarely occur in the hands. The involved tissue was removed with the tumor, with the exception of the tendons and cutaneous nerve. The involved tendon sheath and epineurium were carefully resected. After 2 years of follow-up, the patient showed no signs of tumor recurrence and the hand function was good. IMTs in the hands are relatively rare, and are often easily misdiagnosed as infection. An early and correct diagnosis is the key to successful treatment. A biopsy is necessary following debridement of the infected lesion, particularly for recurrent infected lesions. The surgical approach should be conservative, in order to maintain maximum hand function. PMID- 26137105 TI - 1H nuclear magnetic resonance-based extracellular metabolomic analysis of multidrug resistant Tca8113 oral squamous carcinoma cells. AB - A major obstacle of successful chemotherapy is the development of multidrug resistance (MDR) in the cancer cells, which is difficult to reverse. Metabolomic analysis, an emerging approach that has been increasingly applied in various fields, is able to reflect the unique chemical fingerprints of specific cellular processes in an organism. The assessment of such metabolite changes can be used to identify novel therapeutic biomarkers. In the present study, 1H nuclear magnetic resonance (NMR) spectroscopy was used to analyze the extracellular metabolomic spectrum of the Tca8113 oral squamous carcinoma cell line, in which MDR was induced using the carboplatin (CBP) and pingyangmycin (PYM) chemotherapy drugs in vitro. The data were analyzed using the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) methods. The results demonstrated that the extracellular metabolomic spectrum of metabolites such as glutamate, glycerophosphoethanol amine, alpha-Glucose and beta-Glucose for the drug-induced Tca8113 cells was significantly different from the parental Tca8113 cell line. A number of biochemicals were also significantly different between the groups based on their NMR spectra, with drug-resistant cells presenting relatively higher levels of acetate and lower levels of lactate. In addition, a significantly higher peak was observed at delta 3.35 ppm in the spectrum of the PYM-induced Tca8113 cells. Therefore, 1H NMR-based metabolomic analysis has a high potential for monitoring the formation of MDR during clinical tumor chemotherapy in the future. PMID- 26137106 TI - Integrated analysis of differentially expressed genes in breast cancer pathogenesis. AB - The present study aimed to detect the differences between breast cancer cells and normal breast cells, and investigate the potential pathogenetic mechanisms of breast cancer. The sample GSE9574 series was downloaded, and the microarray data was analyzed to identify differentially expressed genes (DEGs). Gene Ontology (GO) cluster analysis using the GO Enrichment Analysis Software Toolkit platform and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for DEGs was conducted using the Gene Set Analysis Toolkit V2. In addition, a protein-protein interaction (PPI) network was constructed, and target sites of potential transcription factors and potential microRNA (miRNA) molecules were screened. A total of 106 DEGs were identified in the current study. Based on these DEGs, a number of bio-pathways appear to be altered in breast cancer, including a number of signaling pathways and other disease-associated pathways, as indicated by KEGG pathway clustering analysis. ATF3, JUND, FOSB and JUNB were detected in the PPI network. Finally, the most significant potential target sites of transcription factors and miRNAs in breast cancer, which are important in the regulation of gene expression, were identified. The results indicated that miR-93, miR-302A, miR-302B, miR-302C, miR-302D, miR-372, miR-373, miR-520E and miR-520A were closely associated with the occurrence and development of breast cancer. Therefore, changes in the expression of these miRNAs may alter cell metabolism and trigger the development of breast cancer and its complications. PMID- 26137107 TI - Long-term response of gemcitabine plus docetaxel chemotherapy regimen for extraskeletal osteosarcoma: A case report. AB - Extraskeletal osteosarcomas (EOSs) are rare variants of primary osteosarcoma of the bone, and are defined as sarcomas located in the soft tissues and characterized by osteoid production. EOS exhibits distinctive demographic, imaging and prognostic features compared with osteosarcoma of bone origin. The available data are contradictory with regard to the use of chemotherapy regimens in the management of EOS. The present study describes a case of EOS that progressed following two lines of therapy oriented to soft-tissue and bone sarcoma histology, respectively. As a gemcitabine-docetaxel combination schedule has demonstrated synergistic activity against bone and soft-tissue sarcoma histologies, this chemotherapy regimen was selected as salvage therapy. The treatment was well-tolerated and induced a long lasting partial response for ~14 months. To the best of our knowledge, this is the first report involving the clinical use of this combination regimen for the treatment of EOS. Furthermore, as demonstrated in this report, EOS may maintain relative chemosensitivity, indicating the potential to control advanced disease in the long term and to plan subsequent chemotherapy regimens. PMID- 26137108 TI - Heat shock protein 27 promotes cell proliferation through activator protein-1 in lung cancer. AB - Heat shock protein 27 (HSP27) is an important regulator involved in the development of lung cancer. However, limited evidence exists concerning the underlying molecular mechanisms of its action. The results of the present study revealed that HSP27 was highly expressed in the lung cancer tissues of mice. In an in vitro model, the overexpression of HSP27 promoted cell proliferation, while HSP27 knockdown inhibited cell proliferation. HSP27 promoted cell proliferation in vitro by directly upregulating the expression of HSP27 target genes, which required the activation of the activator protein-1 (AP-1) signaling pathway. This was evaluated by the phosphorylation status of an important pathway component, c Jun in lung cancer tissue and cells. These results suggested that HSP27 has a promotional role in lung cancer, and therefore indicated a novel mechanism involving lung cancer cell proliferation, which may underlie poor responses to therapy. Therefore, HSP27 may be a suitable therapeutic target for the treatment of lung cancer. PMID- 26137109 TI - Feasibility of cisplatin/pemetrexed with 15 mg/kg bevacizumab for the treatment of patients with advanced non-squamous non-small cell lung cancer. AB - The aim of the present study was to retrospectively evaluate the feasibility of cisplatin/pemetrexed/bevacizumab (CPB) therapy at a bevacizumab (BEV) dose of 15 mg/kg as a first-line chemotherapeutic strategy for patients with advanced non squamous non-small cell lung cancer (NSCLC). A total of 31 consecutive patients with non-squamous NSCLC were treated with first-line chemotherapy of CPB at a BEV dose of 15 mg/kg at the National Kyushu Cancer Center (Fukuoka, Japan) between November 2009 and December 2011. Clinical characteristics, response rate (RR), progression-free survival (PFS) time, overall survival (OS) time and adverse events were retrospectively analyzed. The 31 patients exhibited a male:female ratio of 21:10 and a median age of 60 years (range, 38-76 years). In total, 5 patients were of clinical stage III and 26 patients were of stage IV, 15 had a performance status of 0 and 16 had a performance status of 1, and 29 patients were diagnosed with adenocarcinoma and 2 were diagnosed with adenosquamous carcinoma. The EGFR mutation status was positive (exon 19 deletion), wild-type and unknown in 3, 21 and 7 patients, respectively. A total of 28 patients (90.3%) received a minimum of four courses of CPB therapy. Hematological toxicities classified as grade III or higher included neutropenia (29.0%), anemia (3.2%) and thrombocytopenia (3.2%), however, no severe non-hematological toxicities were observed. Additionally, 22 patients (71.0%) exhibited a partial response and 9 (29.0%) exhibited stable disease, resulting in a RR of 71.0% [95% confidence interval (CI), 41-74]. The median PFS and OS times were 8.4 months (95% CI, 7.9 9.0) and 28.5 months (95% CI, 26.4-30.6), respectively. Therefore, CPB therapy at a BEV dose of 15 mg/kg appears to be a feasible treatment strategy for patients with advanced non-squamous NSCLC. PMID- 26137110 TI - Successful treatment of quintuple primary cancer, including esophageal cancer: A case report. AB - The present study reports the rare case of a patient with quintuple primary cancer that underwent systematic treatment, including surgical intervention. A 63 year-old male patient was initially diagnosed with primary esophageal cancer and hypopharyngeal cancer. The patient underwent total pharyngolaryngoesophagectomy using a thoracoscopic method and reconstruction using the free jejunal flap and gastric tube and was subsequently administered adjuvant chemotherapy (80 mg/m2 intravenously on day 1, cisplatin; 800 mg/m2 continuous intravenous administration on days 1-5, 5-fluorouracil). At 66 years old, the patient was diagnosed with left maxillary sinus cancer and underwent chemoradiotherapy (four 100 mg/m2 arterial cisplatin injections; 70 Gy/35 f radiotherapy, 2 Gy per day over 35 days). At 68 years old, the patient was diagnosed with gastric tube cancer and underwent gastric tube resection followed by pedicled jejunum flap reconstruction. At 69 years old, the patient was diagnosed with tongue cancer and underwent resection and reconstruction of the tongue by pectoralis major myocutaneous flap. Six years subsequent to the primary surgery, the patient remains alive, without metastasis of the lesions. To the best of our knowledge, the present study is the first report of a patient that underwent a curative procedure for the treatment of five primary multiple cancers in five organs, including esophageal cancer. PMID- 26137111 TI - NF-kappaB inhibitor reverses temozolomide resistance in human glioma TR/U251 cells. AB - Glioblastoma multiforme (GBM) demonstrates an unsatisfactory clinical prognosis due to the intrinsic or acquired resistance to temozolomide (TMZ) exhibited by the tumors. One possible cause of TMZ resistance in GBM is the overexpression of O6-methylguanine-DNA methyltransferase (MGMT), which can repair the TMZ-induced guanine damage in DNA. Additionally, excessive activated NF-kappaB is reported to be a component of the major inflammatory transcription pathway that is associated with TMZ resistance in GBM. However, the association between the NF-kappaB pathway and MGMT expression in GBM cells is unknown. Therefore, in the present study, the TMZ resistant (TR) U251 cell line (TR/U251) was successfully constructed to detect how the TR/U251 cell line and the parental U251 cell line each interact with TMZ in vitro. The TR/U251 cells were approximately five times more resistant to TMZ compared with the parental cells. Furthermore, it was found that the NF-kappaB inhibitor BAY 11-7082 suppressed the expression of MGMT in TR/U251 cells and enhanced TMZ-induced cytotoxicity and apoptosis, thereby indicating that the NF-kappaB pathway and MGMT interact to promote TMZ resistance. The inhibition of NF-kappaB may be a promising strategy to reverse drug resistance in TR glioma cells. The present results propose a potential mechanism for using the NF-kappaB inhibitor BAY 11-7082 as a potential therapy for the treatment of TR glioma. Although BAY 11-7082 is a well-known NF-kappaB inhibitor, the present study further investigated its underlying mechanisms through a series of new experiments. PMID- 26137112 TI - Surgical resection and post-operative radiotherapy in an adult renal neuroblastoma patient with multiple bone and joint metastases: A case report. AB - Renal neuroblastoma is uncommon, particularly in adults, with only a few cases having been reported in studies published in the English language. The incidence is only 0.12 cases/1 million individuals in those aged >20 years. Studies of the pathogenesis, biological characteristics, treatment and prognosis of renal neuroblastoma are limited due to this low incidence. The present study reports the case of a 22-year-old adult female who was diagnosed with a left renal neuroblastoma by computed tomography (CT), bone scan and pathological examination. The patient underwent a left nephroureterectomy, ipsilateral lymph node dissection and post-operative radiotherapy, prior to discharge 60 days after admittance. At the nine-month follow-up examination, the patient showed no evidence of recurrence, progression or metastatic disease on the CT scans of the chest, abdomen and pelvis. Renal neuroblastoma is extremely uncommon in adults. The diagnosis and treatment of renal neuroblastoma is complicated by the overall low incidence, lack of specific treatment guidelines, advanced disease state due to late presentation, and its associated co-morbidities. Further study of the pathogenesis, biological and clinical characteristics, and treatment of renal neuroblastoma is required to provide an optimal treatment for patients and to improve the patient's quality of life. PMID- 26137113 TI - Expression of L1 protein correlates with cluster of differentiation 24 and integrin beta1 expression in gastrointestinal stromal tumors. AB - The present study examined 66 cases of gastrointestinal stromal tumors (GISTs), 20 cases of smooth muscle tumors, 20 cases of schwannomas and 20 cases of normal gastric tissues in order to analyze the expression of L1, cluster of differentiation (CD)24 and integrin beta1 by immunohistochemical staining. Patients were subjected to follow-up, and survival data were evaluated. L1 expression was detected in 57.6% of GIST cases; this was a significantly higher percentage compared with that found in the smooth muscle tumor cases or the normal control group. CD24 and integrin beta1 were also expressed at significantly higher levels in the GIST cases than in the normal control group, although no significant difference was found in the expression levels of these proteins in smooth muscle tumor or schwannoma cases. These higher levels of L1 and integrin beta1 expression were associated with an increased risk of invasive GIST, and were significantly positively correlated with Ki-67 expression. CD24 expression was not associated with the risk of GIST invasion or Ki-67 expression. There were positive correlations between L1, CD24 and integrin beta1 expression; however, these had no significant association with patient survival. Therefore, L1 alone or in conjunction with CD24 (L1 + CD24), or integrin beta1 (L1 + integrin beta1) can be considered a valuable indicator for the differential diagnosis of GIST. Furthermore, L1 and integrin beta1 can be used alone or in combination to evaluate the biological behavior of GISTs. Future studies are required to evaluate the prognostic value of these markers. PMID- 26137114 TI - Detection of CD133 expression in U87 glioblastoma cells using a novel anti-CD133 monoclonal antibody. AB - In glioblastomas, the surface glycoprotein CD133 (prominin-1) indicates the presence of cancer stem cells (CSCs), which are able to initiate tumor growth and are highly resistant to conventional chemo/radiotherapy. However, a number of studies have reported that certain CD133- glioma cells are able to self-renew and retain tumorigenic potential. In addition, the reliability of CD133 as a CSC marker is controversial due to inconsistent findings with regard to the prognostic values and distribution of CD133. Such controversies may be due to the detection limits using currently available anti-CD133 antibodies. In the present study, novel anti-human CD133 monoclonal antibodies (mAbs) were generated using two recombinant extracellular domains of human CD133: CD133 ectodomain 1 (amino acids 171-420) and CD133 ectodomain 2 (amino acids 507-716). One of the antibodies produced against CD133 ectodomain 2, C2E1, detected high expression levels of CD133 protein in glioblastoma U87 cells, in contrast to previous studies which did not detect CD133 expression in these cells. The cells exhibited a cytoplasmic distribution pattern of CD133 and produced a 95 kDa band following western blot analysis. In addition, C2E1 was able to bind the full-length glycosylated CD133 on the cell surface and inhibit the proliferation of tumor cells. Therefore, this antibody may be a valuable tool to study CD133 as a CSC marker and may be significant in future cancer treatments. PMID- 26137115 TI - Experimental research of Fuaile medical adhesive for portal vein embolization in white rabbit models. AB - The aim of the present study was to investigate the feasibility and efficacy of Fuaile medical adhesive for portal vein embolization in the treatment of a rabbit model. This study used 26 white rabbits, 14 of which were selected and assigned into seven groups (n=2) for the preliminary experiment. Fuaile medical adhesive was mixed with lipiodol at different ratios of 1:0, 1:1, 1:2, 1:3, 1:4, 1:5 and 0:1, respectively, and administered via the portal trunk. The remaining 12 white rabbits were randomly divided into two groups (n=6). The evaluation of the results included the degree of adhesion to the vessels, the extent of embolization and the reaction of the rabbit. Hepatic and renal functions were detected prior to and at 1, 7 and 14 days post-embolization, respectively. Angiography, CT scans and pathological examinations were conducted at post embolization. Histological examinations revealed that the topical swollen lesions were darker. Light microscopy showed embolic agents in the portal venous blood vessels and the formation of a secondary thrombus. Hepatic necrosis appeared surrounding the embolization area. Inflammatory cell infiltration of different degrees occurred in the early stage and inflammatory fibroplasia occurred in the late stage. Alanine aminotransferase and aspartate aminotransferase levels increased at 1 day post-embolization, peaked at 7 days and was in the normal range at 14 days. The levels of blood urea nitrogen and ceruloplasmin were elevated at 1 day post-embolization and lowered to normal at 7 days. Fuaile medical adhesive is an effective, safe and inexpensive agent, used for effectively inducing embolization in the portal trunk, and the first and second branches of rabbit portal veins. The use of Fuaile therefore merits widespread application in clinical practice. PMID- 26137116 TI - Amplification and protein expression of androgen receptor gene in prostate cancer cells: Fluorescence in situ hybridization analysis. AB - Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and the second highest cause of cancer-related mortality in adult males worldwide. PCa is highly dependent upon androgen receptor (AR) signaling for cell proliferation and survival. The AR therefore plays a vital role in the development and function of normal and malignant prostate cells or PCa recurrence. The present study aimed to examine the ubiquity of AR amplification in PCa recurrence, even in the absence of androgen. For this purpose, specimens were collected from 37 patients. The amplification of AR and the number of X chromosomes were determined by two colored fluorescence in situ hybridization analysis. The automated image analysis was used to determine the protein expression of AR. Clinical characteristics and survival in patients whose tumors showed or did not show AR amplification and in X-chromosome polysomy with PCa recurrence has also been compared. The results showed that >35% of patients (13 specimens) exhibited AR amplification. It was also observed that AR was immunostained more intensely in the tumors with amplified AR compared with those tumors with non-amplified AR. This study demonstrated an influential role of AR in tumor growth and progression even after the deprivation of androgen, as well as showing the potential contribution of AR amplification to AR activation even in the relative absence of androgen. PMID- 26137117 TI - Primary sternum diffuse large B-cell lymphoma: A case report and review of the literature. AB - Primary bone lymphoma (PBL) is a rare disease, accounting for >1% of all cases of malignant lymphoma. Diffuse large B-cell lymphoma (DLBCL) is the most common histological type of PBL. The present study reported the case of a 68-year-old male with primary bone DLBCL, originally occurred in the sternum, which is a rare form of presentation. Computed tomography (CT), magnetic resonance imaging and bone emission CT were performed, followed by immunohistochemical analysis of a biopsy specimen, and the results were used to establish the diagnosis. At the time of diagnosis, no osseous involvement was observed. The clinical, radiological and histological features of PBL can mimic other medical conditions, thereby making the diagnosis difficult, and frequently leading to delays in treatment. The present study investigated the clinical features, management and prognosis of PBL, and reviewed previous relevant cases. PMID- 26137118 TI - Hemolymphangioma of the waist: A case report and review of the literature. AB - Hemolymphangioma is a malformation of the lymphatic and blood vessels. To the best of our knowledge, only a limited number of hemolymphangioma cases have been reported in the literature thus far, with no cases developed in the waist region. The present study reported the case of a 17-year-old male patient with hemolymphangioma growing on the waist, presented with back pain for four months. Upon physical examination, the lesion was identified to be oval in shape, soft and compressible, with mild tenderness. No abnormalities were detected in the results of laboratory examinations. However, a magnetic resonance imaging (MRI) scan revealed a tumor with low signal intensity on T1-weighted imaging (WI) and high signal intensity on T2-WI. The mass was successfully removed during surgery. During the seven-month follow-up period, the patient was asymptomatic with no evidence of recurrence. The present study discussed the imaging findings and pathological features of this uncommon case and reviewed the relevant literature. PMID- 26137119 TI - Clinical significance of BRAF V600E mutation in 154 patients with thyroid nodules. AB - The aim of the present study was to investigate the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) patients from eastern coastal China and to determine whether it is correlated with the clinicopathological features of PTCs with or without current Hashimoto thyroiditis (HT). The BRAF V600E mutation status was analyzed in 206 thyroid nodules of 154 patients undergoing thyroidectomy using polymerase chain reaction and bi-directional sequencing. Multivariate analysis was performed to investigate the association of the BRAF V600E mutation with clinicopathological features. Thyroid nodules were classified as PTC, nodular goiter (NG), adenomatoid nodule, adenoma and HT. The BRAF V600E mutation was observed in 61.5% of PTCs analyzed; it was also detected in one normal tissue adjacent to PTC and one NG. One patient exhibited double mutations in the BRAF gene; the BRAF V600E mutation in the PTC lesion and the BRAF K601E mutation in the contralateral NG lesion. Patients harboring the BRAF V600E mutation had higher thyroid stimulating hormone levels (2.453+/-1.464 vs. 1.966+/ 1.296 mIU/l), a reduced occurrence of papillary thyroid microcarcinoma (55.0 vs. 88%), and a higher occurrence of lymph node metastasis (LNM; 42.5 vs. 16.0%) compared with those with wild-type BRAF (all P<0.05). Binary logistic regression analysis revealed that the BRAF V600E mutation was associated with LNM of PTC (hazard ratio, 5.051; 95% confidence interval, 1.068-23.893; P=0.041). Conversely, no association was identified between the BRAF V600E mutation and HT (38.5 vs. 67.3%, chi2=3.656, P=0.056). Thus, in regional PTCs, the BRAF V600E mutation was prevalent, suggesting that it may be an early and phenotypically defining molecular event in PTC, and may represent an independent factor that predicts LNM. PMID- 26137120 TI - MicroRNA-203 inhibits cellular proliferation and invasion by targeting Bmi1 in non-small cell lung cancer. AB - MicroRNAs are proposed to serve vital functions in the regulation of tumor progression and invasion. However, the expression levels of miR-203 in non-small cell lung cancer (NSCLC) and its clinical significance remain unknown. In the present study, the association between B-cell-specific moloney murine leukemia virus insertion site 1 (Bmi1) and miR-203 was investigated. miR-203 was demonstrated to act as a tumor suppressor by regulating the expression of Bmi1. miR-203 expression levels were downregulated in NSCLC tissues while Bmi1 expression was upregulated in NSCLC tissues and cell lines. Furthermore, downregulated Bmi1 or enhanced miR-203 expression inhibited NSCLC cell proliferation and invasion in vitro. In addition, a dual-luciferase reporter assay was performed, which identified Bmi1 as a novel target of miR-203. In conclusion, the present study demonstrated that miR-203 functions as a tumor suppressor and is important in inhibiting the proliferation of NSCLC cells through targeting Bmi1. These findings indicate that miR-203 may be useful as a novel potential therapeutic target for NSCLC. PMID- 26137121 TI - Prostate cancer incorrectly diagnosed as a rectal tumor: A case report. AB - Colorectal cancer is the third most commonly diagnosed type of cancer in the world. Prostate adenocarcinoma is the most common male genitourinary tract malignancy, usually occurring after the age of 60. Prostate adenocarcinoma is a highly metastatic cancer. The common metastatic locations of prostate cancer are the bone, lung and liver. The elective locations are bones. Solitary rectal metastasis of prostate cancer is relatively rare. In the present study we report a case of solitary metastasis of a prostate adenocarcinoma with the prostatic capsule intact, which initially led to an incorrect diagnosis. PMID- 26137122 TI - Expression of beta-transducin repeat-containing E3 ubiquitin protein ligase in human glioma and its correlation with prognosis. AB - beta-transducin repeat-containing E3 ubiquitin protein ligase (beta-TrCP) targets a number of substrates essential for specific aspects of tumorigenesis. In addition, beta-TrCP regulates various important signaling pathways. As beta-TrCP is involved in regulating the ubiquitination and degradation of multiple oncogenes and tumor suppressors, the function of beta-TrCP varies between cancer types. At present, the association between beta-TrCP expression and clinicopathological factors in glioma is unknown. Therefore, the current study used western blotting and immunohistochemistry to investigate the expression of beta-TrCP protein in glioma tissue specimens. It was identified that beta-TrCP protein expression levels were significantly lower in glioma compared with non tumorous human brain tissues. Furthermore, the higher the grade of glioma, the lower the level of beta-TrCP expression. Kaplan-Meier analysis demonstrated that patients with low beta-TrCP expression experienced significantly worse overall survival compared with patients with high beta-TrCP expression. The results indicate that downregulation of beta-TrCP may be associated with poor survival in patients with glioma. Together, the current data indicates that beta-TrCP may be applied as a useful indicator of glioma prognosis and may serve as an anticancer therapeutic target for glioma, however further investigation is required. PMID- 26137123 TI - Diagnosis, complications and management of chronic neutrophilic leukaemia: A case report. AB - Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm characterized by sustained neutrophilia and the absence of the Philadelphia chromosome or the BCR-ABL1 fusion gene. The present study reports the case of a 59-year-old Caucasian female that was referred to The Francisco Gentil Portuguese Institute of Oncology (Porto, Portugal) with constitutional symptoms (mainly asthenia), marked leukocytosis (51.33*109/l with 90% neutrophils), macrocytic anemia and splenomegaly. Bone marrow aspiration and biopsy revealed hypercellular marrow with clear predominance of segmented neutrophils. The karyotype was normal and the BCR-ABL1 fusion gene was not detected. After excluding a leukemoid reaction, a diagnosis of CNL was established. The clinical follow-up was complicated by hemorrhagic brain lesions and relapsing episodes of erythematous, well-demarcated and painful subcutaneous nodular lesions, consistent with Sweet's syndrome (SS). Multiple treatment strategies were administered, including use of hydroxyurea, imatinib and intensive chemotherapy. Nevertheless, progression was documented and the patient succumbed at 28 months post-diagnosis. The clinical course of CNL varies, and can be complicated by cerebral hemorrhage, blastic transformation or infection. Dermatological manifestations such as SS have seldom been reported in association. No evidence-based treatment currently exists and the majority of our knowledge is based on results from case reports and small series. PMID- 26137124 TI - Methylation status of the FHIT gene in the transformed human mesenchymal F6 stem cell line. AB - The fragile histidine triad (FHIT) gene is known to be a tumor suppressor gene and the abnormal methylation of FHIT has been identified in leukemia and several solid tumors. The transformation of the tumor F6 cell line from human fetal mesenchymal stem cells (FMSCs) was first reported in a previous study that also identified the presence of a population of cancer stem cells in the F6 cell line. However, the existence of the epigenetic changes during the transformation process have yet to be elucidated. To confirm the role of the FHIT gene in the transformation process of FMSC, the expression level and methylation status of the FHIT gene was examined in F6 tumor cells and FMSCs. Additionally, the alteration in cell morphology, the cell cycle and apoptosis in F6 cells following 5-Aza-CdR treatment was assessed. It was found that the FHIT gene was expressed in FMSCs, but not in F6 cells. The methylation-specific PCR results demonstrated that the promoter methylation of FHIT genes existed in the F6 cell line. Subsequent to treatment with 5-Aza-CdR the expression of FHIT genes was restored in F6 cells. In addition, the morphology of F6 cells was altered, and the cell cycle was arrested in the G2 phase, with the initiation of apoptosis. Overall, the present findings demonstrated that the FHIT gene was methylated in F6 cells and demethylation treatment lead to changes in the biological characteristics, thereby promoting the apoptosis of F6 cells. FHIT gene methylation may be one of the molecular events involved in the development and transformation of FMSCs into F6 tumor cells. PMID- 26137125 TI - Primary mediastinal giant liposarcoma with smooth muscle and neural differentiation: A case report. AB - Liposarcoma has previously been described in Western studies, however, such cases are rarely reported in the mediastinum. In addition, the presence of a liposarcoma with smooth muscle and neural differentiation has not been previously reported. Thus, the present study describes the rare case of a 28-year-old Chinese male admitted to our hospital with the symptoms of chest tightness and shortness of breath due to a recurrent fibrolipoma in the mediastinum. The resected tumor measured 23 cm at its largest diameter, with histopathological and immunohistochemical features indicating a well-differentiated liposarcoma accompanied by smooth muscle and neural differentiation. Following the resection, the patient underwent radiation treatment and remains alive with no evidence of disease recurrence at two months post-surgery. To the best of our knowledge, the present study is the first to report a case of liposarcoma with smooth muscle and neural differentiation, which indicates that liposarcomas could potentially originate from stem cells. The present study highlights the fact that pathologists must carefully investigate the histopathological characteristics of liposarcomas in order to obtain an accurate diagnosis. PMID- 26137126 TI - Focal adhesion kinase is involved in the migration of human osteosarcoma cells. AB - The aim of the present study was to analyze the expression of focal adhesion kinase (FAK) in osteosarcoma (OS) cell lines with different migration abilities in order to determine the role of FAK in migration. A number of different 143B subclone cell lines (A1, A2, A3, A4 and A5) were obtained by a limiting dilution method, and the expression of FAK was detected using western blot analysis. The role of FAK in the migration of OS cells was investigated using small interfering RNA (siRNA), and the ratio of the number of lamellipodia was compared by immunofluorescence staining. The A2 and A3 OS 143B subclone cell lines demonstrated a stronger migration ability and exhibited higher FAK expression compared with the A1 cell line (P<0.05). Following transfection with FAK-siRNA, the migration ability of the A3 cells was significantly decreased (P<0.05), and the ratio of the number of lamellipodia formed was reduced from 35 to 11% (P<0.05). In conclusion, the level of FAK expression was higher in the cell lines with a stronger migration ability. FAK affects the migration ability of OS cells by suppressing the formation of lamellipodia. PMID- 26137127 TI - Acquisition of 5-fluorouracil resistance induces epithelial-mesenchymal transitions through the Hedgehog signaling pathway in HCT-8 colon cancer cells. AB - Colon cancer has a high incidence in individuals >60-years-old. The commonly used chemotherapeutic agent, 5-fluorouracil (5-FU), has gradually lost its potency in treating colorectal cancer following the acquisition of resistance. Drug resistance is usually associated with epithelial-mesenchymal transitions (EMTs) in cancer cells. In the present study, the EMT phenotypes of two colon cancer cell lines, wild-type (HCT-8/WT) and 5-FU-resistant (HCT-8/5-FU), were characterized following the analysis of cellular migration, proliferation, morphology and molecular changes. In order to further clarify the mechanism of EMT in HCT-8/5-FU cells, the effect of EMT pathway inhibitors upon drug sensitivity was investigated. The results revealed that the Hedgehog signaling pathway inhibitor, GDC0449, reversed drug resistance. Therefore, inhibition of the Hedgehog pathway may provide a novel chemotherapeutic strategy for the treatment of patients with 5-FU-resistant colon cancer. PMID- 26137128 TI - Tumor volume reduction rate is superior to RECIST for predicting the pathological response of rectal cancer treated with neoadjuvant chemoradiation: Results from a prospective study. AB - The aim of the present study was to compare the tumor volume reduction rate (TVRR), as determined by three-dimensional region-of-interest magnetic resonance volumetry, and Response Evaluation Criteria in Solid Tumors (RECIST) data for predicting the pathological tumor response (PTR) of locally advanced rectal cancer (LARC) following treatment with neoadjuvant chemoradiation (CRT). The current cohort consisted of 105 patients with LARC [clinical tumor stage (cT)3-4 or clinical lymph node stage (cN)+] from a prospective randomized trial who had undergone pre-operative CRT and radical proctectomy. Tumor volumes were measured prior to and following CRT to determine TVRR. Furthermore, receiver operating characteristic (ROC) curves of TVRR and RECIST were constructed to predict the PTR in terms of tumor regression grade (TRG) and downstaging. Values for the area under the ROC curve (AUC) were compared and TVRR cut-off levels were determined. RECIST was used to identify 5 (4.8%) cases of complete response, 44 (41.9%) of partial response, 55 (52.4%) of stable disease and 1 (0.9%) of progressive disease. The mean TVRR was 58.6+/-24.4%, and a good TRG (0-1) and downstaging occurred in 54 (51.4%) and 59 (56.2%) patients, respectively. In addition, TVRR and RECIST were significantly correlated with TRG and downstaging (P<0.01). The TVRR AUC was significantly larger than that of RECIST for TRG (P=0.020). For downstaging, TVRR also exhibited a larger AUC than RECIST, however, the difference was not significant (P=0.180). The sensitivity and specificity of TVRR in predicting a good TRG were 70.4 and 80.4%, respectively, therefore, the optimal TVRR cut-off value was determined to be 65%. TVRR appeared to be more accurate than RECIST in predicting PTR, particularly for TRG associated with survival. Thus, TVRR may be considered as a novel parameter for evaluating the efficacy of CRT for patients with LARC. PMID- 26137130 TI - Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites. AB - Endostar, a modified recombinant human endostatin, inhibits the growth of a variety of tumors by suppressing neovascularization. Vascular endothelial growth factor (VEGF) has an important role in malignant ascites formation. In order to determine whether Endostar can suppress the formation of ascites and prolong survival times, mouse models of malignant ascites were established using S180 and H22 tumor cells. The experimental mice were randomly divided into four groups: The three treatment groups received different doses of Endostar (4, 8 and 16 mg/kg), and the control group received 0.9% w/v NaCl. The volume of ascites, and the tumor cell, red blood cell (RBC), VEGF protein and mRNA content of the ascites was measured alongside the peritoneal permeability and the mouse survival time. In vitro analysis of cultured Endostar-treated S180 and H22 cells was also performed in order to examine cellular proliferation and the level of VEGF secreted protein and mRNA. The results revealed that Endostar suppressed the ascites volume, decreased the level of tumor cells, RBCs and VEGF in the ascites fluid, and lowered the permeability of the peritoneum. The tumor cells collected from the ascites in the Endostar-treated mice demonstrated a decrease in the expression of VEGF mRNA. The survival rates of the 8 and 16 mg/kg Endostar treated mice were longer than those of the controls. The in vitro experiments revealed a significant inhibition of VEGF protein secretion and VEGF mRNA by Endostar, but no effect on cellular proliferation. In conclusion, Endostar lowers ascites production by downregulating VEGF expression, and may therefore be effective for the treatment of malignant ascites. PMID- 26137129 TI - Bilateral breast cancer following augmentation mammaplasty with polyacrylamide hydrogel injection: A case report. AB - Breast cancer occurring following injection with polyacrylamide hydrogel (PAMG) for augmentation mammaplasty is rare. The present study reports the case of a 43 year-old female presenting with bilateral breast cancer 10 years after augmentation mammaplasty with PAMG injection and no family history of breast cancer. A 5.5*6.0-cm mass in the right breast with multiple intumescent axillary lymph nodes was revealed and a palpable mass of ~1.0 cm was identified in the outer upper quadrant of the left breast. Multiple smaller nodules were observed in the pulmonary field. Pathological examination revealed invasive lobular grade II carcinoma in both breasts with ER(+++), PR(+++), C-erbB2(-), Top-2(+), in the right breast and ER(++), PR(++), c-erb-B2(-), Top-2(+) in the left. Preoperative chemotherapy, modified radical bilateral mastectomy with axillary clearance, postoperative chemotherapy, and an oophorectomy were conducted, followed by treatment with Arimedex(r) until the present date A number of valuable insights can be garnered from this case. First, close follow-up is required for female patients who receive an injection of PAMG for augmentation mammaplasty in order to achieve an early diagnosis and to intervene in any incidences of breast cancer. Second, the differential diagnosis of dual primary carcinoma versus metastatic breast cancer is important and may be aided by the use of molecular technology. Third, it remains difficult to determine gene expression values for the prediction of chemotherapy sensitivity. Thus, discrimination between primary and secondary carcinomas is the principle barrier for identifying an appropriate treatment strategy when a patient is diagnosed with bilateral breast cancer. PMID- 26137131 TI - Giant retroperitoneal bronchogenic cyst mimicking a cystic teratoma: A case report. AB - Retroperitoneal bronchogenic cysts (RBCs) are regarded as a rare type of congenital dysplasia disease that stems from the primitive foregut. Thus far, the exact pathogenesis of RBCs remains unknown. Due to an atypical clinical manifestation, RBCs are often incidentally detected and diagnosed by imaging modalities, such as computed tomography and magnetic resonance imaging. However, they are easily misdiagnosed due to their non-specific imaging features. Additionally, the most appropriate treatment strategy for an RBC is considered to be surgical resection. The present study reports the rare case of a 36-year-old female with a large RBC containing fatty fluid that was previously misdiagnosed as liposarcoma or cystic teratoma. Following a complex surgical resection, pathological findings confirmed a diagnosis of RBC. The follow-up examination showed that the patient was in good health at 16 months post-surgery, with no evidence of recurrence. Although rare, bronchogenic cysts must be considered in the differential diagnosis of retroperitoneal teratoma, and surgical resection should be pursued for symptom resolution and to establish a definitive histology. PMID- 26137132 TI - Clinical features and prognosis-associated factors of non-small cell lung cancer exhibiting symptoms of bone metastasis at the time of diagnosis. AB - The present study aimed to analyze the clinical characteristics and prognosis related factors of non-small cell lung cancer (NSCLC) patients with bone metastases at the time of diagnosis. A total of 46 NSCLC patients with skeletal metastases at the time of diagnosis from Anhui Provincial Hospital and Anhui Provincial Cancer Hospital Affiliated to Anhui Medical University (Hefei, China) between February 2010 and February 2012 were investigated retrospectively. The median age was 58 years, with a range of 40-80 years, the ratio of males and females was 2:1, and adenocarcinoma and squamous cell carcinoma accounted for 71.7 and 28.3% of cases, respectively. Furthermore, 84.8% of patients exhibited multiple skeletal metastases at more than two sites and 54.3% of patients experienced skeletal-related events at the time of diagnosis. The median overall survival (OS) time of the patients was 237 days, and Kaplan-Meier analysis demonstrated that patients with adenocarcinoma (P=0.002), single bone metastases (P=0.023), an Eastern Cooperative Oncology Group performance status of 0-1 (P<0.001) or positive expression of estrogen receptor (ER)-beta (P=0.039) exhibited significantly longer survival times. Furthermore, multivariate analysis identified the following independent predictors of OS: Tumor subtype (P=0.022), the number of bone metastases (P=0.016) and an ER-beta-positive tumor (P=0.035). In the cohort of NSCLC patients with bone metastases at the time of diagnosis, adenocarcinoma and multiple skeletal metastases were most common. PMID- 26137133 TI - Primary malignant melanoma of the pleura with rapid progression: A case report and literature review. AB - A primary melanocytic lesion arising from the pleura is a rare occurrence. This is the case report of a 36-year-old female patient with a primary pleural melanocytic tumor. The positron emission tomography/computed tomography scan revealed multiple nodular soft tissue thickenings of the left hemipleura and a large amount of pleural effusion in the left hemithorax. The results of the histological examination confirmed the diagnosis of melanoma. The disease progressed 4 months following immunotherapy and chemotherapy and the patient succumbed to the disease 2 months later. This type of tumor appears to exhibit a highly aggressive biological behavior and responds poorly to immunotherapy and chemotherapy, which are characteristics similar to those exhibited by melanomas arising in other regions. PMID- 26137134 TI - Comparison of the clinical value of multi-band mucosectomy versus endoscopic mucosal resection for the treatment of patients with early-stage esophageal cancer. AB - The present study aimed to compare the clinical value of multi-band mucosectomy (MBM) versus endoscopic mucosal resection (EMR) for the treatment of patients with early-stage esophageal cancer. Between January 2011 and December 2012, 68 patients with early-stage esophageal cancer who underwent MBM and EMR were enrolled into the present study. The curative resection rate, duration of surgery, complications and follow-up records were retrospectively analyzed. Of the 68 patients included, 33 were treated with MBM and 35 with EMR. There was no significant difference in the rate of complete resection between the MBM and EMR groups (P>0.05). The mean duration of surgery in the MBM group was statistically lower than that in the EMR group (P<0.05). There was no statistically significant difference in the intraoperative and post-operative complications between the MBM and EMR groups (P>0.05). Esophageal cancer reoccurred in 2 patients treated with MBM and 1 patient treated with EMR during the follow-up period (range, 3-24 months). Overall, MBM can be considered a better surgical option for the management of patients with early-stage esophageal cancer, as it offers higher histological curative resection rates and improved safety. However, further studies and a larger follow-up period are required to confirm the long-term curative effect. PMID- 26137135 TI - Scutellaria barbata D. Don polysaccharides inhibit the growth of Calu-3 xenograft tumors via suppression of the HER2 pathway and angiogenesis. AB - Scutellaria barbata D. Don, a perennial herb belonging to the family Lamiaceae, is widely distributed throughout China and the Republic of Korea, and has been traditionally used in folk medicine as an antitumor and anti-inflammatory agent. Polysaccharides isolated from Scutellaria barbata D. Don (PSB), have been reported to possess antitumor effects. However, the detailed antitumor mechanisms behind the effects of PSB remain unclear. In the present study, a non-small cell lung cancer cell line harboring the HER2 gene mutation Calu-3, the Calu-3 cell line, was used to investigate the underlying mechanisms of the antitumor effects of PSB. The results revealed that PSB potently inhibited cell proliferation and human epidermal growth factor receptor (HER)2 phosphorylation in vitro, and also downregulated the expression of the downstream signaling molecules, including phosphorylated (phospho-)Akt and phospho-extracellular signal-related kinase. In vivo, PSB demonstrated efficacy at well-tolerated doses, including significant antitumor activity in a Calu-3 subcutaneous xenograft model. Immunohistochemistry (IHC) analysis revealed a PSB dose-dependent reduction of microvessel density, demonstrated by cluster of differentiation 31 staining. The present findings suggest that inhibition of tumor angiogenesis via suppression of the HER2 pathway may be one of the mechanisms by which PSB can be effective in the treatment of cancers. PMID- 26137136 TI - Primary pericardial extragastrointestinal stromal tumor: A case report and literature review. AB - Gastrointestinal stromal tumors (GISTs) are the most prevalent mesenchymal tumors of the gastrointestinal tract. GISTs are considered to originate from the interstitial cells of Cajal, the pacemakers of the peristaltic activity of the gastrointestinal tract. More than 95% of GISTs express KIT protein and discovered on GIST-1. GISTs may also be encountered in locations outside the gastrointestinal tract, in which case they are referred to as extra-GISTs (EGISTs) and often behave more aggressively. This is the case report of a primary pericardial EGIST in a 53-year-old male patient, confirmed by immunohistochemistry. To the best of our knowledge, this is the third case of EGIST diagnosed above the diaphragm, without being associated with the esophageal wall. Two cases of primary EGIST arising from the pleura were reported previously. In addition, this is the first reported case of an EGIST originating from the pericardium. PMID- 26137137 TI - Construction of the plasmid coding for the expression of the EGFP-M-IL-2(88Arg, 125Ala) fusion protein and the anti-tumor effects exerted by the fusion protein in HeLa-60 cells. AB - Gene therapy is a promising therapeutic option for the treatment of various cancers, and tumor-targeted plasmids encoding toxic protein genes are potential tools for gene therapy. In the present study, a recombinant plasmid containing the genes for the toxic protein melittin and interleukin-2 (IL-2) was constructed. Melittin and IL-2 are known to play key roles in immunoregulation and cancer therapy, but they each possess defects that limit the clinical application of these proteins. The present study aimed to construct a novel recombinant expression plasmid, pLEGFP-C1-M-IL-2(88Arg, 125Ala), and to improve the biological activity of IL-2 and melittin. The M-IL-2(88Arg, 125Ala) gene was excised from the pPICZalphaA/M-IL-2(88Arg, 125Ala) plasmid by polymerase chain reaction (PCR). The pLEGFP-C1 plasmid carrying the enhanced green fluorescent protein (EGFP) gene was used as a shuttle plasmid. Subsequent to digestion, the M IL-2(88Arg, 125Ala) gene was subcloned into the pLEGFP-C1 vector to build the pLEGFP-C1-M-IL-2(88Arg, 125Ala) eukaryotic expression plasmid, which was identified by restriction enzyme digestion and gene sequencing. Confocal microscopy was used to determine the transfection efficiency subsequent to the plasmid being transfected into the cervical cancer HeLa cell line. The cells transfected with the pLEGFP-C1-M-IL-2(88Arg, 125Ala) plasmid demonstrated a decreased transfection efficiency compared with the cells transfected with the pLEGFP-C1 plasmid. The cellular expression of M-IL-2(88Arg, 125Ala) was detected by reverse transcription PCR and western blot analysis. Finally, cell counting kit-8 and apoptosis assays were performed to investigate the effects of the expression of the M-IL-2(88Arg, 125Ala) fusion protein on HeLa cells and to analyze the antitumor activity of the protein. In conclusion, a recombinant eukaryotic pLEGFP-C1-M-IL-2(88Arg, 125Ala) expression plasmid containing the M-IL 2(88Arg, 125Ala) fusion gene was constructed and the M-IL-2(88Arg, 125Ala) fusion protein was successfully expressed in HeLa cells. Furthermore, the M-IL-2(88Arg, 125Ala) fusion protein was able to inhibit HeLa cell proliferation and induce apoptosis in the tumor cells. These findings may offer an alternative method for anticancer therapy. The present study has provided a basis for future studies into the M-IL-2(88Arg, 125Ala) fusion gene. PMID- 26137138 TI - Role of autophagy in the omega-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells. AB - The present study identified that omega-3 long chain polyunsaturated fatty acids (omega-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrate anti-proliferative effects in lung cancer A549 cells. MTS and cytotoxicity assays were conducted to confirm that omega-3 PUFAs induced cell death. Autophagy-associated gene and signaling pathways were also detected. Microtubule-associated protein light chain 3 (LC3) expression was found to be increased subsequent to treatment with DHA and EPA, and the expression of LC3-II was particularly increased. mRFP-GFP-LC3 fluorescence staining and p62 expression levels were used to detect autophagic flux. The present results indicate that DHA and EPA block autophagic flux, suggesting autophagosome accumulation. Subsequent to treatment with DHA and EPA, which interfered with autophagosomes, the expression of Beclin 1 was significantly decreased, while the expression of phosphorylated Akt and phosphorylated mammalian target of rapamycin was significantly increased. Therefore, DHA and EPA exert anti-proliferative effects by inhibiting autophagy in A549 cells, which highlights the potential of DHA and EPA for use in the prevention or treatment of lung cancer. PMID- 26137139 TI - miR-218 inhibits the proliferation of glioma U87 cells through the inactivation of the CDK6/cyclin D1/p21Cip1/Waf1 pathway. AB - Malignant gliomas are the most common and deadly primary brain tumors in adults and the high proliferative ability of these cells is one of the most important causes of the poor prognosis of this cancer. Suppressing the proliferation of malignant gliomas cells by altering effector molecules can significantly improve the prognosis of a patient. microRNAs (miRNAs) are small non-coding RNA molecules ~22 nucleotides in length that are able to function as oncogenes or tumor suppressors in human cancer. In the present study, it was demonstrated that the expression level of miRNA-218 (miR-218) is markedly downregulated in glioma cell lines and human primary glioma tissues. Upregulation of miR-218 in glioma U87 cells dramatically inhibited the proliferation by inducing G1-S checkpoint arrest. Furthermore, it was demonstrated that ectopically expressing miR-218 in glioma U87 cells results in the downregulation of the expression of cyclin dependent kinase (CDK)6 and cyclin D1 and upregulation of the expression of p21Cip1/Waf1. In addition, it was identified that miR-218 inactivated the CDK6/cyclin D1/p21Cip1/Waf1 pathway by downregulating CDK6 expression through the direct targeting of the 3'-untranslated region of CDK6. The present results suggest that miR-218 plays an important role in the prevention of the proliferation of glioma cells, and the present study also revealed a novel mechanism for miRNA-mediated direct suppression of the CDK6/cyclin D1/p21Cip1/Waf1 pathway in glioma cells. PMID- 26137140 TI - Overexpression of Notch1 is associated with the progression of cervical cancer. AB - Cervical cancer is the third most common malignancy worldwide, accounting for 250,000 mortalities annually. Notch1, an important regulator of cell-fate decisions and differentiation, has been found to be overexpressed in certain types of cancer. However, the role of Notch1 in cervical carcinogenesis remains unclear. In the present study, immunohistochemical staining and western blot analysis revealed that Notch1 expression was significantly higher in cervical cancer tissues than that in normal cervical tissues. Furthermore, statistical analysis revealed that Notch1 expression was significantly associated with tumor differentiation and tumor stage. These findings indicated that Notch1 expression was associated with the progression of cervical cancer. The western blot assay also identified a positive correlation between Notch1 and Ki67 expression in cervical cancer tissues, which suggested that Notch1 expression may be associated with the proliferation of cervical cancer. In order to further evaluate the specific role of Notch1 in cervical cancer progression, its expression in SiHa and C33A cells was knocked down using small interfering RNA. It was revealed that the knockdown of Notch1 in SiHa and C33A cells resulted in significant inhibition of cell proliferation and colony formation in vitro. These results indicated that Notch1 was able to promote cell proliferation in cervical cancer. In conclusion, the results of the present study indicated that Notch1 may function as a promoter in cervical carcinogenesis. PMID- 26137141 TI - Overexpression of cofilin 1 in prostate cancer and the corresponding clinical implications. AB - Cofilin 1 (CFL1) is a cytoskeletal protein and overexpression of the protein has been associated with aggressiveness in certain types of malignancies. The aim of the present study was to investigate the clinical implications of CFL1 expression in prostate cancer (PCa). Immunohistochemical analysis was performed using formalin-fixed paraffin-embedded tissue sections obtained from 111 patients with PCa and 47 patients with benign prostatic hyperplasia (BPH). In total, 78 (70.3%) out of 111 PCa tissues were found to express the CFL1 protein, while no expression was detected in BPH tissues. In addition, CFL1 was also observed to be significantly associated with the Gleason score (GS; <7 vs. >=7; P<0.0001) and presence of lymph node metastasis (presence vs. absence; P<0.0001). However, there was no association between the expression of CFL1 and other clinicopathological variables, such as age (<69 years vs. >=69 years; P=0.54), pre-operative prostate specific antigen level (<20 ng/ml vs. >=20 ng/ml; P=0.45) and pathological stage (T2 vs. >=T3a; P=0.055). In addition, 35 tissues (31.5%) were observed to possess a CFL1-positive mesenchyme. CFL1 expression was revealed to be an independent predictive factor for a high GS. The status of CFL1 expression in the mesenchyme also found to individually predict extraprostatic extension in PCa patients, based on multivariate analysis. The results of the present study indicated that CFL1 may specifically predict the development of PCa, and that the expression of CFL1 in the mesenchyme may be closely associated with the development of lymph node metastasis. PMID- 26137142 TI - Pituitary lesions in breast cancer patients: A report of three cases. AB - Pituitary metastases occur in 6-8% of breast cancer cases, but are seldom diagnosed and rarely reported. Therefore, it can be challenging to establish a clinical differential diagnosis, and at present, a definitive criteria is not available. The present study discusses the pituitary lesions identified in three patients with breast cancer, and describes their management within the collaborative framework of the Breast Unit at the Citta della Salute Hospital, which also included assessment by endocrinologists. The patients were evaluated for anterior and posterior pituitary function, the appearance of the pituitary upon magnetic resonance imaging (MRI), and the oncology status and treatment. In addition, successive analysis of prolactin levels and the MRI was performed. The patients, aged 75, 83 and 76 years old, differed in their clinical presentation and successive evolution. One patient demonstrated an abrupt onset of diabetes insipidus, the second exhibited overt hypopituitarism and the final patient had a pituitary mass discovered by chance. Cases one and three exhibited systemic spread of the breast cancer, with bone and/or parenchymal metastasis, but not brain metastasis. Case two presented with a secondary pituitary tumour alone. In case three, a secondary nature to the pituitary lesion was unlikely, since there was no lesion evolution evident following MRI and as stable prolactin levels were observed over the course of the study period. By contrast, case one presented with a rapid increase of sellar lesions on MRI, together with a progressive rise in prolactin levels. Taking into account the frailty of breast cancer patients who are monitored for disease progression, management in a collaborative framework, such as at the Breast Unit, makes it possible to establish a diagnosis of sellar lesions, which is adequate for the comprehensive management of the patient with successive pituitary MRIs and prolactin evaluations, and avoids unnecessary invasive neurosurgery. PMID- 26137143 TI - RACK1 expression contributes to JNK activity, but JNK activity does not enhance RACK1 expression in hepatocellular carcinoma SMMC-7721 cells. AB - Receptor for activated C kinase 1 (RACK1) is up-regulated in hepatocellular carcinoma (HCC) and has been reported to augment c-Jun N-terminal protein kinase (JNK) activity in HCC SMMC-7721 cells. By contrast, activator protein-1, a downstream JNK transcription factor, has been revealed to mediate the overexpression of RACK1 in melanoma cells. Therefore, the association between RACK1 and JNK activity in HCC cells has yet to be completely elucidated. The present study analyzed the effects of RACK1 or JNK loss of function on the levels of RACK1 protein, JNK activity, cell proliferation and apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand in HCC SMMC-7721 cells. It was found that JNK loss of function exhibited no effect on RACK1 expression, whereas a loss of RACK1 function led to reduced JNK activity in SMMC-7721 cells. RACK1 and JNK loss of function resulted in the impaired oncogenic growth of SMMC-7721 cells. The present data further support a pivotal role of RACK1 in mediating enhanced JNK activity in HCC cells and also indicate that a novel mechanism exists for RACK1 overexpression in HCC SMMC-7721 cells. PMID- 26137144 TI - MED12 mutation in patients with hysteromyoma. AB - Mediator Complex Subunit 12 (MED12) is a subunit of the mediator complex, which is believed to regulate global, as well as gene-specific, transcription. It has been reported that MED12 is mutated at high frequency in hysteromyoma. Recent studies have also shown that MED12 presents with different mutation frequencies in hysteromyoma patients of different populations. However, there are few studies with regard to the MED12 gene mutation in hysteromyoma patients in the Chinese Han population. In the present study, the MED12 mutations of 171 patients with hysteromyoma were analyzed; the results showed that 93 patients exhibited different MED12 mutations, including 131G->T, 131G->A, 130G->A, 146C->T, 130G->A, 130G->C, 128A->C, 130G->T, 127Ins27, 118_132Del15, 117_134Del18, 131_148Del18 and 141_165Del15. The mutation frequency was similar to that found in individuals of African descent or individuals of other non-Caucasian ethnicities, and lower than that in the Finnish or North American populations. Further analysis of 141 patients whose hysteromyoma was measured showed that the mutation frequency of MED12 in patients with large hysteromyomas was significantly lower than that in those with small hysteromyomas. These results suggested that MED12 mutation was important in the development of hysteromyomas in the Chinese Han population and that the size of the hysteromyoma may negatively correlate with the mutation frequency of MED12. This study supplemented current information on MED12 mutations in different races and may aid in developing personalized diagnoses for patients with hysteromyoma in the future. PMID- 26137145 TI - Application of percutaneous vertebroplasty in the treatment of multiple thoracic metastases. AB - The present study aimed to explore the clinical implications of percutaneous vertebroplasty (PVP) in the treatment of multiple thoracic metastases. A total of 104 involved vertebrae of 28 patients with multiple thoracic metastases underwent PVP and the injection of bone cement. The pain relief rate and activity of daily life were assessed, and the morphological changes of the involved vertebral bodies and the invasiveness of the intraspinal tumor were also observed at 1 week, and 3, 6 and 12 months post-surgery, respectively. The pain relief rate increased at each time-point following PVP. The quality of life scores were also significantly higher than the pre-operative scores. After 12 months of follow-up, the post-operative heights of the anterior border, center and posterior border of the vertebral bodies were not noted to be statistically different from those prior to PVP (P>0.05). The present study concluded that PVP has a good analgesic effect on multiple thoracic metastases. PVP not only improves the quality of life of patients significantly, but also prevents further vertebral collapse and the invasiveness of intraspinal tumors, avoiding the nerve dysfunction caused by spinal cord compression. PMID- 26137146 TI - Type II cyclic guanosine monophosphate-dependent protein kinase inhibits epidermal growth factor receptor activation in different cancer cell lines. AB - Previous data has revealed that type II cyclic guanosine monophosphate-dependent protein kinase (PKG II) inhibits epidermal growth factor (EGF)-induced phosphorylation/activation of the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) in gastric cancer cells. The aim of the present study was to determine whether PKG II inhibited EGF-induced phosphorylation/activation of EGFR and MAPK/ERK in cell lines derived from different cancer tissues. SW480, HepG2, OS-RC-2, A549, MCF-7 and U251 cells were transfected with adenoviral constructs encoding PKG II cDNA (Ad-PKG II) to upregulate the expression of PKG II, and then treated with 8 (4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP) in order to activate the kinase. Western blot analysis was performed to investigate the phosphorylation of EGFR and MAPK/ERK. The results demonstrated that treatment with 100 ng/ml EGF for 5 min increased the tyrosine (Tyr)1068 phosphorylation of EGFR and the threonine 202/Tyr204 phosphorylation of MAPK/ERK. Transfecting the cells with Ad-PKG II, and stimulating the kinases with 8-pCPT-cGMP efficiently inhibited the EGF-induced phosphorylation of EGFR and MAPK/ERK. The results revealed that PKG II had an inhibitory effect upon EGFR activation and the consequent MAPK/ERK-mediated signaling of cell lines derived from the various cancer tissues. PMID- 26137147 TI - Double PALB2 and BRCA1/BRCA2 mutation carriers are rare in breast cancer and breast-ovarian cancer syndrome families from the French Canadian founder population. AB - French Canadian families with breast cancer and breast-ovarian cancer syndrome harbor specific BRCA1, BRCA2 and PALB2 germline mutations, which have been attributed to common founders. Mutations in these genes confer an increased risk to breast and ovarian cancers, and have been identified to play a role in and directly interact with the common homologous recombination DNA repair pathways. Our previous study described the case of a female diagnosed with breast cancer at 45 years old, who harbored the PALB2:c.2323C>T [p.Q775X] and BRCA2:c.9004G>A [p.E3002K] germline mutations, which have been found to recur in the French Canadian cancer families. As the frequency of double heterozygous carriers of breast-ovarian cancer susceptibility alleles is unknown, and due to the possibility that there may be implications for genetic counseling and management for these carriers, the present study investigated the co-occurrence of BRCA1/BRCA2 and PALB2 mutations in the French Canadian cancer families. The PALB2:c.2323C>T [p.Q775X] mutation, which is the only PALB2 mutation to have been identified in French Canadian cancer families, was screened in 214 breast cancer cases and 22 breast-ovarian cancer cases from 114 BRCA1/BRCA2 mutation-positive French Canadian breast cancer (n=61) and breast-ovarian cancer (n=53) families using a tailored polymerase chain reaction-based TaqMan(r) SNP Genotyping Assay. No additional PALB2:c.2323C>T [p.Q775X] mutation carriers were identified among the BRCA1/BRCA2 mutation carriers. The results suggest that carriers of the PALB2:c.2323C>T [p.Q775X] mutation rarely co-occur in French Canadian breast cancer and breast-ovarian cancer families harboring BRCA1 or BRCA2 mutations. PMID- 26137148 TI - Response of adenocarcinoma of the uterine cervix to chemoradiotherapy. AB - The aim of the current retrospective study was to investigate the response of advanced cervical adenocarcinoma (AC) to definitive chemoradiotherapy. Uterine cervical cancer is one of the most common cancer types among females, with squamous cell carcinoma (SQCC) being the most prevalent histological type. The incidence of cervical AC and its variants has markedly increased in recent decades. The current understanding with regard to the treatment of cervical cancer has been established through studies in which the majority of the patients suffered from SQCC, while only a limited number of studies have focused on the treatment of AC. Therefore, the optimal treatment for uterine cervical AC remains unclear. In the present study, data were collected from the medical files of patients who were diagnosed with advanced uterine cervical AC and treated with chemoradiotherapy between 1998 and 2013. Data were also collected from a group of patients with SQCC for comparison with AC patients in terms of response and survival. A total of 68 uterine cervical cancer cases were included, including 29 AC patients and 39 SQCC patients. Compared with the SQCC subgroup, a higher number of AC patients required surgery following chemoradiotherapy due to a lack of response to the initial treatment (5% vs. 31%, respectively; P=0.0065). After a median follow-up period of 10 years, patients with AC exhibited shorter overall survival (7.4 years vs. 11 years for AC and SQCC groups, respectively; P=0.01). Differences in recurrence (40.7% vs. 34.4%; P=0.79) and disease-free interval (1.2 years vs. 2 years; P=0.11) were not statistically significant. The results indicated that cervical AC is less responsive to chemoradiotherapy compared with SQCC. PMID- 26137149 TI - Analysis of AC3-33 gene expression in multiple organ cancer and adjacent normal tissue by RNA in situ hybridization. AB - The AC3-33 gene encodes a secretory protein that can inhibit Elk1 transcriptional activity via the ERK1/2 pathway. In the current study, in situ RNA hybridization was used to detect the AC3-33 gene expression in multiple organ cancer and cancer adjacent normal tissue. The results showed that the expression level of AC3-33 varies across different tissues. AC3-33 exhibited positive expression in squamous cell carcinoma of the esophagus, adenocarcinoma of the rectum, hepatocellular carcinoma, squamous cell carcinoma (SCC) of the lung, cancer-adjacent normal hepatic tissue, clear cell carcinoma of the kidney, invasive ductal carcinoma of the breast, SCC of the uterine cervix and cancer-adjacent normal kidney tissue. Negative expression of AC3-33 was observed in adenocarcinoma of the stomach and colon, cancer-adjacent normal esophageal tissue, cancer-adjacent normal gastric tissue, cancer-adjacent normal colon tissue, cancer-adjacent normal rectal tissue, serous adenocarcinoma of the ovary and cancer-adjacent normal ovarian tissue. However, the expression of AC3-33 in cancer adjacent normal breast tissue was partially positive. In conclusion, the AC3-33 gene does exhibit positive expression in certain carcinomas, which may indicate that AC3-33 has a significant involvement in the development and progression of these carcinomas. PMID- 26137150 TI - Expression of aquaporin 5 in primary carcinoma and lymph node metastatic carcinoma of non-small cell lung cancer. AB - Aquaporin 5 (AQP5), a water channel protein, is highly expressed in non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues. AQP5 expression in lung cancer tissues is associated with a poor prognosis. The present study aimed to analyze the expression of AQP5 and investigate its role in primary and lymph node metastatic NSCLCs. An immunohistochemical labeled streptavidin-biotin method was used to determine the expression of AQP5 in 94 cases of NSCLC primary carcinoma, which included 51 cases accompanied by lymph node metastasis. The results revealed that the expression of AQP5 was significantly higher in adenocarcinomas compared with squamous cell carcinomas (P=0.002). In addition, the percentage of AQP5 expression in the primary carcinomas with lymph node metastasis was significantly higher compared with those without lymph node metastasis (P=0.024). However, no statistically significant difference in the percentage of AQP5 expression was observed between the metastatic and the primary carcinomas (P=0.377). The expression of AQP5 exhibited a correlation with the tumor-node-metastasis staging of NSCLC (P=0.027). The percentage of AQP5 expression in stage III and IV tumors was higher than that in stage I and II tumors. In addition, AQP5 expression was correlated with the survival rate of NSCLC patients (P=0.051). In conclusion, the results of the present study provide evidence for the AQP5-facilitated incidence, progression and metastasis of NSCLC. Therefore, AQP5 may be used as a potential target to investigate the incidence, progression and metastasis of NSCLC. PMID- 26137151 TI - Omental transplantation improves surgical outcome of large squamous cell carcinoma: A case report. AB - Cutaneous squamous cell carcinoma (SCC) is an major health issue due to the significant health costs and marked disfigurement following surgical excision. The conventional reconstructive options may not be suitable for patients with large SCCs of the lower part of the leg, due to the regional tissue damage and ischemic environment. The omental transposition flap is a highly vascularized tissue that is resistant to infection and provides a recipient bed for skin grafts. This is the case report of a male patient with a large SCC in the lower part of his right leg, which was treated with extensive resection. The patient subsequently underwent reconstruction using a free omental flap, followed by transplantation of a secondary skin graft. The patient did not experience recurrence or metastasis during the 2 years of follow-up, indicating that, when dealing with postoperative skin cancer defects in an ischemic environment, omental transplantation may be a viable treatment option. PMID- 26137152 TI - Glucose transporter 3 performs a critical role in mTOR-mediated oncogenic glycolysis and tumorigenesis. AB - The present study aimed to examine the relationship between mammalian target of rapamycin (mTOR) and glucose transporter 3 (Glut3) in the process of mTOR mediated oncogenic glycolysis and tumorigenesis. Western blot analysis and quantitative polymerase chain reaction were used to compare the expression of Glut3 in mouse embryonic fibroblasts (MEFs) null for tuberous sclerosis complex 2 (Tsc2-/-) and control Tsc2+/+ MEFs. In addition, the glycolytic rate was tested following siRNA-mediated knockdown of Glut3 in Tsc2-/- cells. To determine whether Glut3 depletion affects the ability of cells to form tumors in vivo. Tsc2 /- MEFs infected shGlut3 and shControl were injected into nude mice subcutaneously. The present study demonstrated that the expression of Glut3 is controlled by mTOR in Tsc2-/- cells and that downregulation of Glut3 reduced the glycolytic rate in Tsc2-/- cells. cells. Further studies in nude mice demonstrated that reduced Glut3 expression levels reduced the tumorigenetic effect in cells with hyperactive mTOR complex 1 (mTORC1). The present study indicates for the first time that Glut3 is a downstream target of mTORC1 and that Glut3 is critical in mTORC1-associated tumorigenesis. Therefore, Glut3 is a potential target for the treatment of diseases associated with dysregulated mTORC1 signaling. PMID- 26137153 TI - Anaplastic large cell lymphoma with primary involvement of the skeletal muscle: A case report. AB - The present study reported the case of a patient with primary anaplastic large cell lymphoma (ALCL) occurring in the left major psoas. A 24-year-old male patient presented with one-month history of left lower back pain, which had been exacerbated for 10 days prior to admission. Magnetic resonance imaging (MRI) scans revealed an enlarged major psoas muscle that protruded into the inguinal region. The presence of an intense soft tissue mass on MRI scans, as well as the results of fine-needle aspiration biopsy and immunohistochemical analysis of the mass, may help establish an early diagnosis, allowing for the appropriate treatment strategy to be initiated. PMID- 26137154 TI - Increased serum tumor necrosis factor receptor-associated factor-6 expression in patients with non-metastatic triple-negative breast cancer. AB - Obesity appears to be associated with an increased risk of breast cancer (BC) and an inferior oncological outcome at the time of diagnosis, with poor outcomes most prominent in cases of triple-negative BC (TNBC). The present study analyzed serum tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and TNF receptor associated factor-6 (TRAF) protein expression levels in 48 patients with non-metastatic BC and 26 obese control patients (without BC). The mean age of the cohort was 52.5 years (range, 35-78 years) and the patients had a median body mass index of 33.5 kg/m2 (range, 30-47 kg/m2). In the study population, 27.1% of BC patients were triple negative and 70.8% were hormone receptor (HR)-positive. Median serum TRAF6 expression was 0.90 ng/ml (range, 0.55-1.53 ng/ml) in the 13 TNBC patients and 0.63 ng/ml (range, 0.49-1.22 ng/ml) in the 35 HR-positive BC patients; thus, TRAF6 expression was significantly higher in the TNBC patients compared with the obese control group (0.90 vs. 0.73 ng/ml; P=0.033). Furthermore, median serum TRAF6 expression levels were significantly higher in HR negative patients compared with HR-positive patients (0.83 vs. 0.62 ng/ml; P=0.002). The present study demonstrated that serum TRAF6 expression levels were increased in TNBC and HR-negative patients with non-metastatic BC compared with HR- and human epidermal growth factor receptor 2-positive cases or the obese healthy control group. Therefore, elevated TRAF6 expression may be a poor prognostic factor in non-metastatic BC. In addition, we propose that progesterone (PR) negativity may be a more useful poor prognosis factor than estrogen receptor (ER) negativity, as TRAF6 expression levels were higher in the PR-negative patients compared with the ER-negative patients. PMID- 26137155 TI - Effect of neoadjuvant chemotherapy in patients with triple-negative breast cancer: A meta-analysis. AB - The present meta-analysis aimed to evaluate the effect of neoadjuvant chemotherapy on pathological complete response (pCR) and survival rate in patients with triple-negative breast cancer (TNBC). Specific inclusion and exclusion criteria were used to conduct a search of the available databases, in order to find studies performed between January 2006 and January 2014. The bibliographies of the included studies were examined with the same criteria. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group framework was used to evaluate the included studies, and RevMan 5.1 and GRADEprofiler 3.6 were used to analyze the extracted data. A total of 19 studies with 6,180 patients were included. The meta-analysis revealed that the pCR rates in patients with TNBC were significantly higher than those in patients with non TNBC. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly lower in the patients with TNBC compared with those with non-TNBC. Furthermore, these survival rates were significantly higher in the patients with TNBC who achieved a pCR compared with those in the patients who did not achieve a pCR. pCR rates were higher among the patients with TNBC with high Ki-67 expression than among those with low Ki-67 expression. The patients with TNBC exhibited lower survival rates compared with those with non-TNBC, but achieved higher pCR rates. Moreover, those patients achieving a pCR exhibited improved 5 year survival rates, suggesting that the pCR rate could be predictive of survival in patients with TNBC. In addition, high Ki-67 expression may predict the likelihood of a pCR. However, future multicenter randomized controlled trials are required to enhance the quantity and quality of the clinical evidence. PMID- 26137156 TI - All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro. AB - All-trans retinoic acid (ATRA) is a derivative of vitamin A that can induce differentiation and apoptosis, as well as inhibit proliferation, in glioma cells. However, the effect of ATRA on the migration and invasiveness of glioma remains poorly understood. In addition, although it is universally accepted that ATRA can induce apoptosis and inhibit proliferation in glioma cells, the association between the concentration and effects of ATRA remain unclear. Therefore, the present study investigated the effects of ATRA treatment on the migration, invasion, apoptosis and proliferation of glioma cells. The U87 and SHG44 glioma cell lines were treated with various concentrations of ATRA, consisting of 0, 5, 10, 20 and 40 umol/l. A scratch wound healing assay and a Matrigel invasion assay were used to investigate cell migration and invasion, respectively. Flow cytometry was performed to investigate apoptosis and cell cycle distribution. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to investigate the expression of matrix metalloproteinase (MMP)-2 and 9 in each cell treatment group. Following treatment with ATRA, the migration, invasion and proliferation of the glioma cells were significantly inhibited, and the apoptosis rate was significantly increased compared with that of the blank control group. Furthermore, a dose-effect association was identified between each effects and ATRA treatment. The mRNA and protein expression of MMP-2 in U87 glioma cells was not significantly affected following treatment with low concentrations of ATRA, consisting of 5 and 10 umol/l ATRA, compared with the expression in the control group (P>0.05). However, treatment with high concentrations of ATRA, consisting of 20 and 40 umol/l ATRA, significantly downregulated the expression levels of MMP-2 in U87 cells. In contrast to U87 cells, the administration of ATRA treatment to SHG44 glioma cells resulted in a significant and dose-dependent downregulation in MMP-2 mRNA and protein expression (P<0.01). In addition, significant downregulation of MMP-9 expression was identified in the two glioma cell lines (P<0.01). The results of the present study indicate that treatment with ATRA may inhibit migration, invasion and proliferation, and promote apoptosis in glioma cells. Furthermore, the current study indicates that the inhibition of glioma cell invasion by ATRA may be partially associated with its effect ability to downregulate MMP expression. PMID- 26137157 TI - Genomic losses at 5q13.2 and 8p23.1 in dysplastic hepatocytes are common events in hepatitis B virus-related hepatocellular carcinoma. AB - Chromosomal loci with genomic imbalances are frequently identified in hepatocellular carcinoma (HCC). Greater than two-thirds of hepatitis B virus (HBV)-related HCCs originate from liver cirrhosis following a duration of up to two decades. However, it is unclear whether these genomic imbalances occur and accumulate in dysplastic hepatocytes of the cirrhotic liver during the progression from regenerated nodules to preneoplastic lesions, including dysplastic nodules (DN). In the present study, high-grade DNs (HGDNs) of HBV related liver cirrhosis were screened to identify loci with genomic imbalances, and the frequency of the identified loci in a group of HCCs was analyzed in order to determine whether there may be a genetic link between liver cirrhosis and HCC. Genomic DNA was extracted from six HGDNs of two cases of HBV-related liver cirrhosis and subjected to array comparative genomic hybridization (CGH) analysis with a NimbleGen 720K microarray. Loci with the most frequently observed genomic imbalances in DNs were further analyzed in 83 cases of HCC by differential polymerase chain reaction (PCR) and quantitative PCR. The array CGH analysis revealed that the majority of genomic imbalances in the HGDNs were genomic losses of small segments, with loss of heterozygosity (LOH) at 5q13.2 and 8p23.1 identified most frequently. Of the 83 HCC cases, 30 (36.1%) cases were identified with LOH at 5q13.2, where known tumor-associated genes are located, including general transcription factor IIH subunit 2 (GTF2H2), baculoviral IAP repeat containing protein 1 (BIRC1) and occludin (OCLN). LOH frequency at 8p23.1 in HCC was 61.29% (D8S1130) and 68.4% (D8S503) respectively, similar to the results obtained in previous studies. In conclusion, the results of the present study provided evidence that genomic losses at 5q13.2 and 8p23.1 identified in dysplastic hepatocytes of the cirrhotic liver are common events in HCC. HCC associated chromosomal abnormalities may occur and accumulate in preneoplastic lesions of liver cirrhosis. PMID- 26137158 TI - Expression of Smad4, TGF-betaRII, and p21waf1 in esophageal squamous cell carcinoma tissue. AB - Esophageal squamous cell carcinoma (SCC) possesses one of the worst prognoses out of the digestive carcinomas. Several studies have suggested that transforming growth factor beta receptor type II (TGF-betaRII), Smad family member 4 (Smad4) and p21 wild-type p53-activated factor 1 (p21waf1) are associated with esophageal SCC. The aim of the present study was to evaluate the effect of Smad4, TGF betaRII and p21waf1 in esophageal squamous cancer tissue and the pathological significance of the effect. An immunohistochemical method was used to evaluate the expression levels of Smad4, TGF-betaRII and p21waf1 in specimens of esophageal SCC lesions obtained from 80 patients. It was found that the expression of Smad4, TGF-betaRII and p21waf1 in histologically-classified grade I esophageal SCC, without invasion or lymph node metastasis, was markedly higher compared with grade III esophageal SCC that had invaded into the deep muscular or serous layer and metastasized to the lymph nodes (P<0.05). Analysis of the expression level of Smad4, TGF-betaRII and p21waf1, as well as the clinical and pathological characteristics of esophageal SCC, revealed that the three proteins may be associated with the carcinogenesis, biological behavior and prognosis of esophageal SCC, parallel to the pathological stage and cell grade. PMID- 26137159 TI - Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells. AB - Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions. PMID- 26137160 TI - LGR5 promotes the proliferation of colorectal cancer cells via the Wnt/beta catenin signaling pathway. AB - Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is an established cancer stem cell marker and is a target gene of the Wnt/beta-catenin signaling pathway, a critical pathway in the process of tumor initiation and growth. In the present study, the mRNA expression levels of LGR5, adenomatous polyposis coli (APC) and beta-catenin were detected in 20 colorectal cancer (CRC) tissues and matched healthy mucosa samples using reverse transcription quantitative polymerase chain reaction. HT-29 CRC cell line was treated with siRNA-Lgr5; the APC, beta-catenin and LGR5 RNA expressions were detected and cell viability was measured using a CCK8 assay. The results revealed that LGR5 was significantly overexpressed in CRC tissue compared with healthy mucosa (P<0.05). Furthermore, knockdown of LGR5 by small interfering RNA decreased the expression of APC and beta-catenin in HT29 colon cancer cells as well as inhibited the proliferation of HT29 cells. These findings demonstrated that LGR5 expression is critical for the promotion of neoplastic CRC cell proliferation, indicating that LGR5 may be a novel therapeutic target for CRC. PMID- 26137161 TI - S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells. AB - S100 calcium-binding protein B (S100B) is highly expressed in glioma cells and promotes cancer cell survival via inhibition of the p53 protein. In melanoma cells, this S100B-p53 interaction is known to be inhibited by pentamidine isethionate, an antiprotozoal agent. Thus, the aim of the present study was to evaluate the effect of pentamidine on rat C6 glioma cell proliferation, migration and apoptosis in vitro. The change in C6 cell proliferation following treatment with pentamidine was determined by performing a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide-formazan assay. Significant dose-dependent decreases in proliferation were observed at pentamidine concentrations of 0.05 uM (58.5+/ 5%; P<0.05), 0.5 uM (40.6+/-7%; P<0.01) and 5 uM (13+/-4%; P<0.001) compared with the control (100% viability). Furthermore, treatment with 0.05, 0.5 and 5 uM pentamidine was associated with a significant increase in apoptosis versus the untreated cells, as determined by DNA fragmentation assays, immunofluorescence analysis of C6 chromatin using Hoechst staining, and immunoblot analysis of B cell lymphoma-2 (Bcl-2)-associated X protein (100%, P<0.05; 453%, P<0.01; and 1000%, P<0.001, respectively) and Bcl-2 (-60%, P<0.001; -80.13%, P<0.001; -95%, P<0.001, respectively). In addition, the administration of 0.05, 0.5 and 5 uM pentamidine significantly upregulated the protein expression levels of p53 (681+/ 87.5%, P<0.05; 1244+/-94.3%, P<0.01; and 2244+/-111%, P<0.001, respectively), and significantly downregulated the expression levels of matrix metalloproteinase-2 (42+/-2.3%, P<0.05; 71+/-2.5%, P<0.01; and 95.8+/-3.3%, P<0.001, respectively) and aquaporin 4 (38+/-2.5%, P<0.05; 69+/-2.6%, P<0.01; and 88+/-3.0%, P<0.001, respectively), compared with the untreated cells. The wound healing assay demonstrated that cell migration was significantly impaired by treatment with 0.05, 0.5 and 5 uM pentamidine compared with untreated cells (88+/-4.2%, P<0.05; 64+/-2%, P<0.01; and 42+/-3.1%, P<0.001, respectively). Although additional in vivo studies are required to clarify the current in vitro data, the present study indicates that pentamidine and S100B-p53 inhibitors may represent a novel approach for the treatment of glioma. PMID- 26137162 TI - Failure of matrix metalloproteinase-9 dimer induction by phorbol 12-myristate 13 acetate in normal human cell lines. AB - Increasing experimental and clinical data has identified an association between increased levels of matrix metalloproteinase (MMP)-9 and shortened patient survival, cancer progression and metastasis. MMP-9 has a significant role in tumor cell invasion and metastasis, as it digests the basement membrane and components of the extracellular matrix. MMP-9 is secreted in either a monomeric or dimeric form. Although limited evidence exists concerning MMP-9 dimers, certain studies have demonstrated that the dimer is associated with aggressive tumor progression. This is believed to be due to the fact that cellular migration depends upon the MMP-9 dimer, and not the monomer. Our previous study revealed that cancer cell MMP-9 dimer secretion patterns could be divided into different categories, and that high MMP-9 and MMP-9 dimer secretion levels were correlated with the most aggressive cancer cell lines. It has been established that signal transduction pathways and cytokines, including those activated by phorbol 12 myristate 13-acetate (PMA), regulate the expression of MMPs. The aim of the present study was to analyze the expression patterns of MMP-2, MMP-9 and MMP-9 dimer in normal human cells from a number of tissues treated with PMA. Muscle, epithelial and connective tissues were selected for use in the present study, since adenosarcomas, carcinomas and sarcomas are derived from these tissue types, respectively. The cell lines were first cultured in 24-well tissue culture plates containing recommended media that was supplemented with 10% fetal bovine serum and antibiotics. When at confluency, the cells were washed and fresh medium was added. In addition, a parallel set of cultures was treated with PMA. Subsequent to a 24-h incubation period, the media were collected and analyzed using gelatinase zymography for the expression of MMP-2 and MMP-9 monomer and dimer forms. The results revealed that the cellular expression of MMP-2 and MMP-9 was dependent upon the primary tissue subtype. All cell lines, regardless of tissue origin, expressed MMP-2. PMA induced the expression of MMP-9 in muscle tissue, glandular epithelia and supportive connective tissue cell lines. By contrast, cell lines of endothelial origin and proper connective tissue were insensitive to treatment with PMA. MMP-9 dimer secretion was not observed in any of the cell lines, which indicated that cellular migration is not supported by these cells. PMID- 26137163 TI - Advanced squamous lung carcinoma in a patient experiencing long-term survival following repeated responses to gemcitabine and cisplatin chemotherapy: A case report. AB - The cisplatin and gemcitabine regimen is one of the most effective regimens against advanced non-small-cell lung cancer. However, tumors that are initially sensitive to chemotherapy treatment may acquire drug resistance. Excision repair cross complementation 1 gene (ERCC1) is involved in the repair of DNA damage caused by cisplatin, and ribonucleotide reductase M1 subunit (RRM1) is associated with gemcitabine resistance in tumor cells. The current study reports the case of a patient with advanced squamous cell lung carcinoma exhibiting low ERCC1 and RRM1 expression levels, who experienced long-term survival following repeated responses to gemcitabine and cisplatin chemotherapy. This case indicates that selected patients may benefit from multiple courses of gemcitabine and cisplatin chemotherapy, and the sustained clinical benefits suggest that further investigation into individualized therapy is merited. PMID- 26137164 TI - Relative quantitative expression of hypoxia-inducible factor-1alpha, -2alpha and 3alpha, and vascular endothelial growth factor A in laryngeal carcinoma. AB - The aim of the present study was to determine the relative quantitative expression of hypoxia-inducible factor (HIF)-1alpha, -2alpha and -3alpha, and VEGF-A in laryngeal carcinoma. A total of 63 patients with carcinoma of the larynx were enrolled in the study. Total RNA was isolated from fresh, frozen normal and tumor tissues of each patient, and quantitative polymerase chain reaction was performed. HIF-1alpha was upregulated in the majority of patients (44 patients; 69.84%). By contrast, only 7 (11.11%) patients from the whole group displayed HIF-2alpha overexpression, while the HIF-3alpha isoform was silenced in the majority of patients (48 patients, 76.19%). A small group of 5 (7.94%) patients exhibited significant overexpression of the HIF-3alpha isoform. VEGF-A expression was significantly higher (P<0.05) in patients with upregulated HIF 1alpha (2.72+/-1.41 RQ) compared with patients without upregulated HIF-1alpha (1.86+/-1.46 RQ). There was a moderate positive correlation between mRNA expression levels of HIF-1alpha and VEGF-A (rs=0.392; P<0.005). To the best of our knowledge, this study is first to report quantitative data with regard to the expression of all three HIF isoforms in malignant neoplasms. The findings suggest the existence of specific phenotypes of HIF expression in laryngeal carcinoma, where the HIF switch is absent. PMID- 26137166 TI - Securin promotes migration and invasion via matrix metalloproteinases in glioma cells. AB - Human securin, encoded by pituitary tumor transforming gene 1, is implicated in several oncogenic processes in the pathogenesis of brain tumors, including glioma. The aim of the present study was to examine the effect of securin on the migration and invasion of glioma cells. The results revealed that the overexpression of securin in glioma LN-229 cells significantly increased the invasion and transmigration abilities. By contrast, these abilities were significantly reduced by the downregulation of securin in glioma U373 cells. Furthermore, the results demonstrated that securin overexpression and downregulation significantly increased and decreased the levels of matrix metalloproteinase 2 and 9, respectively. These findings indicate a promotive role for securin in glioma migration and invasion, which may involve the action of matrix metalloproteinases. PMID- 26137165 TI - Relative mRNA expression of prostate-derived E-twenty-six factor and E-twenty-six variant 4 transcription factors, and of uridine phosphorylase-1 and thymidine phosphorylase enzymes, in benign and malignant prostatic tissue. AB - Prostate cancer is the most frequent urological tumor, and the second most common cancer diagnosed in men. Incidence and mortality are variable and appear to depend on behavioral factors and genetic predisposition. The prostate-derived E twenty-six factor (PDEF) and E-twenty-six variant 4 (ETV4) transcription factors, and the thymidine phosphorylase (TP) and uridine phosphorylase-1 (UP-1) enzymes, are reported to be components of the pathways leading to tumorigenesis and/or metastasis in a number of tumors. The present study aimed to analyze the mRNA expression levels of these proteins in prostatic cancerous and benign tissue, and their association with clinical and pathological variables. Using quantitative reverse transcription polymerase chain reaction, the mRNA expression levels of PDEF, ETV4, TP and UP-1 were studied in 52 tissue samples (31 of benign prostatic hyperplasia and 21 of prostate adenocarcinomas) obtained from patients treated by transurethral resection of the prostate or by radical prostatectomy. Relative expression was assessed using the ?-CT method. Data was analyzed using Spearman's tests for correlation. P<0.05 was considered to indicate a statistically significant difference. The results revealed that PDEF, ETV4, UP-1 and TP were expressed in 85.7, 90.5, 95.2 and 100% of the prostate cancer samples, and in 90.3, 96.8, 90.3 and 96.8% of the benign samples, respectively. PDEF and ETV4 exhibited a significantly higher relative expression level in the tumor samples compared with their benign counterparts. The relative expression of TP and UP-1 did not differ significantly between benign and cancerous prostate tissues. The relative expression of TP was moderately and significantly correlated with the expression of ETV4 in the benign tissues. The relative expression of UP-1 was significantly lower in T3 compared with T1 and T2 cancers. These findings indicate that PDEF, ETV4, TP and UP-1 are typically expressed in benign and malignant prostatic tissues. Further studies are necessary to define the role of these proteins as therapeutic targets in prostate cancer. PMID- 26137167 TI - Collecting duct carcinoma of the kidney: A case report. AB - Collecting duct carcinoma (CDC) is a rare type of renal tumor, arising from the distal collecting ducts. The prognosis of this disease is extremely poor due to its rapid progression with widespread metastases. The present study reported a case of CDC involving the right renal region of a 62-year-old female patient, presented with right-flank pain that had persisted for one month. A computed tomography scan demonstrated multiple hypoattenuating quasicircular lesions, 0.5 4.3 cm in size, in the upper pole of the right kidney. Following the diagnosis of a right renal tumor, laparoscopic radical resection of the right kidney was performed. Pathological examination demonstrated that the tumor cells were arranged in a glandular or papillary pattern, and marked cytological atypia was observed. Immunohistochemical staining revealed that the tumor cells were positive for epithelial membrane antigen and cytokeratin (CK)7, while they reacted focally with vimentin. However, the tumor cells were negative for CK20, CD10, uroplakin III and p63. Based on these findings, the patient was diagnosed with CDC. In conclusion, immunohistochemical analysis is critical in establishing an accurate diagnosis of CDC and distinguishing this tumor from other subtypes of RCC. PMID- 26137168 TI - Doxorubicin activates the Notch signaling pathway in osteosarcoma. AB - Notch signaling is critical in various biological processes, including cell proliferation, differentiation and apoptosis. Furthermore, accumulating evidence indicated that aberrant Notch signaling has a tumor-promoting function in osteosarcoma. However, the effect of the conventional chemotherapeutic agent, doxorubicin, on Notch signaling remains unclear. In the present study, osteosarcoma cells were treated with various concentrations of doxorubicin and the effect on Notch signaling was analyzed. A cytostatic dose of doxorubicin (<0.5 uM) was identified to significantly activate the Notch signaling pathway in a dose-dependent manner (P<0.01), as demonstrated by the elevated expression levels of Notch target genes. However, a toxic dose of doxorubicin (>=0.5 uM) significantly inhibited the Notch signaling pathway (P<0.01). These results indicated a significant correlation between doxorubicin administration and the Notch signaling pathway. Therefore, the present study supports further investigation into Notch and osteosarcoma chemoresistance. PMID- 26137169 TI - Hybrid-polymerase chain reaction to identify novel target genes of miR-134 in paclitaxel resistant human ovarian carcinoma cells. AB - Increasing evidence has shown that miR-134 is involved in the promotion of tumorigenesis and chemoresistance. However, whether miR-134 participates in ovarian cancer chemoresistance and its functional targets still remains unclear. The objective of this study was to apply hybrid-polymerase chain reaction (PCR) to screen target genes of miR-134 in ovarian carcinoma paclitaxel resistant SKOV3 TR30 cells, and to provide a number of novel targets of miR-134 for further study of ovarian cancer paclitaxel resistance. The current study found that miR-134 was decreased in SKOV3-TR30 cells compared with the parental SKOV3 cell line. By applying hybrid-PCR, 8 putative target genes of miR-134 in SKOV3-TR30 cells were identified, including C16orf72, PNAS-105, SRM, VIM, F-box protein 2, GAPDH, PRPF6 and RPL41. Notably, the target sites of VIM and PRPF6 were not located in 3'untranslated region, but rather in the coding sequence region. By conducting a luciferase reporter assay, miR-134 was demonstrated to recognize the putative binding sites of these target genes including VIM and PRPF6. Transfecting SKOV3 TR30 cells with miR-134 mimic and performing reverse transcription-PCR in addition to western blot analysis confirmed that miR-134 regulates vimentin expression at a post transcriptional level. This finding provides a novel perspective for studying the mechanism of miR-134/mRNA interaction. In conclusion, this study was the first to apply an effective method of hybrid-PCR to screen putative target mRNAs of miR-134 in paclitaxel resistant SKOV3-TR30 cells and indicate that miR-134 may contribute to the induction of SKOV3-TR30 paclitaxel resistance by targeting these genes. PMID- 26137171 TI - Adaptive and Unstructured Mesh Cleaving. AB - We propose a new strategy for boundary conforming meshing that decouples the problem of building tetrahedra of proper size and shape from the problem of conforming to complex, non-manifold boundaries. This approach is motivated by the observation that while several methods exist for adaptive tetrahedral meshing, they typically have difficulty at geometric boundaries. The proposed strategy avoids this conflict by extracting the boundary conforming constraint into a secondary step. We first build a background mesh having a desired set of tetrahedral properties, and then use a generalized stenciling method to divide, or "cleave", these elements to get a set of conforming tetrahedra, while limiting the impacts cleaving has on element quality. In developing this new framework, we make several technical contributions including a new method for building graded tetrahedral meshes as well as a generalization of the isosurface stuffing and lattice cleaving algorithms to unstructured background meshes. PMID- 26137170 TI - Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms. AB - BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common micro deletion syndrome. The associated 22q11.2 deletion conveys the strongest known molecular risk for schizophrenia. Neurodevelopmental phenotypes, including intellectual disability, are also prominent though variable in severity. Other developmental features include congenital cardiac and craniofacial anomalies. Whereas existing mouse models have been helpful in determining the role of some genes overlapped by the hemizygous 22q11.2 deletion in phenotypic expression, much remains unknown. Simple model organisms remain largely unexploited in exploring these genotype-phenotype relationships. METHODS: We first developed a comprehensive map of the human 22q11.2 deletion region, delineating gene content, and brain expression. To identify putative orthologs, standard methods were used to interrogate the proteomes of the zebrafish (D. rerio), fruit fly (D. melanogaster), and worm (C. elegans), in addition to the mouse. Spatial locations of conserved homologues were mapped to examine syntenic relationships. We systematically cataloged available knockout and knockdown models of all conserved genes across these organisms, including a comprehensive review of associated phenotypes. RESULTS: There are 90 genes overlapped by the typical 2.5 Mb deletion 22q11.2 region. Of the 46 protein-coding genes, 41 (89.1 %) have documented expression in the human brain. Identified homologues in the zebrafish (n = 37, 80.4 %) were comparable to those in the mouse (n = 40, 86.9 %) and included some conserved gene cluster structures. There were 22 (47.8 %) putative homologues in the fruit fly and 17 (37.0 %) in the worm involving multiple chromosomes. Individual gene knockdown mutants were available for the simple model organisms, but not for mouse. Although phenotypic data were relatively limited for knockout and knockdown models of the 17 genes conserved across all species, there was some evidence for roles in neurodevelopmental phenotypes, including four of the six mitochondrial genes in the 22q11.2 deletion region. CONCLUSIONS: Simple model organisms represent a powerful but underutilized means of investigating the molecular mechanisms underlying the elevated risk for neurodevelopmental disorders in 22q11.2DS. This comparative multi-species study provides novel resources and support for the potential utility of non-mouse models in expression studies and high-throughput drug screening. The approach has implications for other recurrent copy number variations associated with neurodevelopmental phenotypes. PMID- 26137172 TI - Keep on Walking. PMID- 26137173 TI - Internal Rotation Behind-the-Back Angle: A Reliable Angular Measurement for Shoulder Internal Rotation Behind the Back. AB - BACKGROUND: The hand-behind-back method is the accepted technique to evaluate shoulder internal rotation, is highly popular, and is endorsed by the American Academy of Orthopaedic Surgeons. It remains, however, subject to intra- and interexaminer discrepancy and has been challenged by several recent publications. HYPOTHESIS: Internal rotation behind the back can be evaluated with a measurable angle, which eliminates the need to estimate spinal level, decreases the effect of unrelated joints, and allows collection of numeric rather than categoric data. STUDY DESIGN: Descriptive laboratory study. METHODS: We defined the internal rotation behind-the-back (IRB) angle as that between the ulna and the line of gravity. A pendulum is attached to a standard goniometer. The patient is asked to reach the highest point along the midline of the back. The goniometer is centered over the pisiform, and the angle between the ulnar axis and the pendulum is measured. Two examiners assessed both shoulders of 60 volunteers with no shoulder pathology using this technique on 2 occasions. Both examiners were blinded to each other's values. We applied the paired Student t test and calculated Pearson correlation coefficients and weighted Cohen kappa values. RESULTS: The IRB angles ranged from 50 degrees to 125 degrees . The difference of the mean, as measured with the Student t test, was 0.6 degrees (95% confidence interval: 0.1 degrees , 1.3 degrees ) and 0.6 degrees (95% confidence interval: -0.8 degrees , 1.8 degrees ); the Pearson correlation coefficients were 0.98 and 0.92; and the weighted kappa values were 0.88 and 0.77 for interobserver and intraobserver analyses, respectively. CONCLUSION: The IRB angle is easy to measure, is reproducible, and does not rely on determination of spinal level. It provides numeric data and may eliminate some of the uncertainty associated with the estimation of spinal level. CLINICAL RELEVANCE: The IRB angle may eliminate some of the uncertainty associated with the estimation of spinal level. PMID- 26137174 TI - A Systematic Review and Meta-analysis Comparing Clinical Outcomes After Concurrent Rotator Cuff Repair and Long Head Biceps Tenodesis or Tenotomy. AB - CONTEXT: A comparison of clinical outcomes after long head of biceps (LHB) tenotomy or tenodesis performed concurrently with rotator cuff repair (RCR) is of interest to physicians and patients. OBJECTIVE: A systematic review of clinical outcome studies examining LHB tenotomy or tenodesis performed concurrently with RCR. Secondarily, perform a meta-analysis of data from comparative studies. DATA SOURCES: MEDLINE (1946 to week 30 of 2013) and EMBASE (1980 to week 30 of 2013). STUDY SELECTION: Levels 1 through 4 studies reporting clinical outcomes of concurrent RCR and LHB tenotomy or tenodesis with minimum 1-year follow-up. STUDY DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Two independent reviewers identified eligible studies and applied the exclusion criteria. Clinical outcome data, including functional outcome score(s), biceps deformity and cramping, and patient satisfaction, were extracted. Clinical outcome data from included studies were pooled (weighted according to study size) and reported. A meta-analysis was performed only on outcomes extracted from comparative studies (alpha = 0.05). RESULTS: Twelve studies (N = 565 patients; mean age, 61.3 years; 46.3% men) were included. Of these, 6 (N = 263) included RCR and LHB tenotomy and 9 (N = 302) included RCR and LHB tenodesis. A meta analysis was performed on 3 comparative studies (levels 1 and 2), demonstrating that the postoperative Constant score at a mean follow-up of 25.5 months was significantly greater after tenodesis (92.8 [tenodesis] vs 90.6 [tenotomy], P < 0.01); however, this difference was less than the reported minimal clinically important difference of 10.4 points. Similarly, the rate of biceps deformity was significantly less after tenodesis (15.5% [tenotomy] vs 3.9% [tenodesis], P < 0.01); however, most patients were not bothered by it. There were no significant differences in the rate of biceps cramping or patient satisfaction. CONCLUSION: Although the postoperative Constant score and rate of biceps deformity favor LHB tenodesis statistically, the clinical significance appears negligible. PMID- 26137175 TI - Olecranon Stress Injury in an Adolescent Overhand Pitcher: A Case Report and Analysis of the Literature. AB - Upper extremity stress fractures, which are relatively rare, have become increasingly common, with olecranon stress injuries representing a subset primarily affecting throwing athletes. Olecranon stress fractures have been classified to fit specific radiographic patterns, with most of these injuries typified by a fracture line. Only a handful of olecranon stress injury cases report magnetic resonance imaging findings of osseous edema within the olecranon, as in our case of a 17-year-old competitive overhand baseball pitcher with elbow pain. The patient was treated conservatively and had resolution of pain after 6 weeks of rest, followed by a 6-week throwing progression with full return to pitching. PMID- 26137176 TI - Reliability of a New Clinical Instrument for Measuring Internal and External Glenohumeral Rotation. AB - BACKGROUND: The shoulder plays a critical role in many overhead athletic activities. Several studies have shown alterations in shoulder range of motion (ROM) in the dominant shoulder of overhead athletes and correlation with significantly increased risk of injury to the shoulder and elbow. The purpose of this study was to measure isolated glenohumeral joint internal/external rotation (IR/ER) to determine inter- and intraobserver reliability of a new clinical device. HYPOTHESIS: (1) Inter- and intraobserver reliability would exceed 90% for measures of glenohumeral joint IR, ER, and total arc of motion; (2) the dominant arm would exhibit significantly increased ER, significantly decreased IR, and no difference in total arc of motion compared with the nondominant shoulder; and (3) a significant difference exists in total arc between male and female patients. STUDY DESIGN: Case series. LEVEL OF EVIDENCE: Level 4. METHODS: Thirty-seven subjects (mean age, 23 years; range, 13-54 years) were tested by 2 orthopaedic surgeons. A single test consisted of 1 arc of motion from neutral to external rotation to internal rotation and back to neutral within preset torque limits. Each examiner performed 3 tests on the dominant and nondominant shoulders. Each examiner completed 2 installations. RESULTS: Testing reliability demonstrated that neither trial, installation, nor observer were significant sources of variation. The maximum standard deviation was 1.3 degrees for total arc of motion and less than 2 degrees for most other measurements. Dominant arm ER was significantly greater than nondominant arm ER (P = 0.02), and dominant arm IR was significantly less than nondominant arm IR (P = 0.00). Mean total rotation was 162 degrees , with no significant differences in total rotation between dominant and nondominant arms (P = 0.34). Mean total arc of motion was 45 degrees greater in female subjects. Differences in total arc of motion between male and female subjects was statistically significant (P < 0.00). CONCLUSION: This simple, clinical device allows for both inter- and intraobserver reliability measurements of glenohumeral internal and external rotation. PMID- 26137177 TI - A Case of Posterior Sternoclavicular Dislocation in a Professional American Football Player. AB - Sternoclavicular (SC) dislocation is a rare injury of the upper extremity. Treatment of posterior SC dislocation ranges from conservative (closed reduction) to operative (open reduction with or without surgical reconstruction of the SC joint). To date, we are unaware of any literature that exists pertaining to this injury or its treatment in elite athletes. The purpose of this case report is to describe a posterior SC joint dislocation in a professional American football player and to illustrate the issues associated with its diagnosis and treatment and the athlete's return to sports. To our knowledge, this case is the first reported in a professional athlete. He was treated successfully with closed reduction and returned to play within 5 weeks of injury. PMID- 26137178 TI - A Comparison of Rehabilitation Methods After Arthroscopic Rotator Cuff Repair: A Systematic Review. AB - CONTEXT: Despite the significant attention directed toward optimizing arthroscopic rotator cuff repair, there has been less focus on rehabilitation after rotator cuff repair surgery. OBJECTIVE: To determine the effect of different rehabilitation protocols on clinical outcomes by comparing early versus late mobilization approaches and continuous passive mobilization (CPM) versus manual therapy after arthroscopic rotator cuff repair. DATA SOURCES: PubMed was searched for relevant articles using the keywords rotator cuff, rotator, cuff, tears, lacerations, and rehabilitation to identify articles published from January 1980 to March 2014. STUDY SELECTION: Inclusion criteria consisted of articles of level 1 or 2 evidence, written in the English language, and with reported outcomes for early versus late mobilization or rehabilitation with CPM versus manual therapy after primary arthroscopic rotator cuff repair. Exclusion criteria consisted of articles of level 3, 4, or 5 evidence, non-English language, and those with significantly different demographic variables between study groups. Included studies were evaluated with the Consolidated Standards of Reporting Trials criteria. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 2. DATA EXTRACTION: Level of evidence, study type, number of patients enrolled, number of patients at final follow-up, length of follow-up, age, sex, rotator cuff tear size, surgical technique, and concomitant operative procedures were extracted from included articles. Postoperative data included clinical outcome scores, visual analog score for pain, shoulder range of motion, strength, and rotator cuff retear rates. RESULTS: A total of 7 studies met all criteria and were included in the final analysis. Five studies compared early and late mobilization. Two studies compared CPM and manual therapy. CONCLUSION: In general, current data do not definitively demonstrate a significant difference between postoperative rotator cuff rehabilitation protocols that stress different timing of mobilization and use of CPM. PMID- 26137179 TI - Impaired Femoral Vascular Compliance and Endothelial Dysfunction in 30 Healthy Male Soccer Players: Competitive Sports and Local Detrimental Effects. AB - BACKGROUND: Despite beneficial effects of physical activity on cardiovascular risk, discordant data on elite athletes (high atherosclerotic damage in activity comprising strenuous exertion) and retired sportsmen are reported in the literature. HYPOTHESIS: We hypothesize that long-lasting daily physical activity could affect the morphology and function of the carotid and femoral vessel walls differently, as assessed in elite male athletes aged 20 to 30 years compared with age- and sex-matched healthy controls. STUDY DESIGN: Retrospective case-control study. LEVEL OF EVIDENCE: Level 3. METHODS: Sixty male subjects (30 athletes and 30 controls) underwent medical examination for ankle brachial index, augmentation index (AIX) and AIX corrected for heart rate (AIXr), peripheral arterial tonometry (PAT), and intima media thickness and pulse wave velocity assay at common carotid (carotid-intima media thickness [c-IMT], carotid-pulse wave velocity [c-PWv]) and femoral arteries (femoral-intima media thickness [f-IMT], femoral-pulse wave velocity [f-PWv]) assessed by ultrasonography using Doppler ultrasound. RESULTS: Athletes showed a significantly lower heart rate (HR) at rest and a better lipid profile than controls. In athletes, c-PWv (5.87 +/- 0.80 vs 6.62 +/- 1.02 m/s, P = 0.001) and f-PWv (8.96 +/- 1.29 vs 7.89 +/- 1.39, P = 0.002) were, respectively, significantly lower and higher than values found in controls; accordingly, carotid AIX (4.03 +/- 6.21 vs 7.81 +/- 5.21, P = 0.003) and femoral AIX (8.56 +/- 10.21 vs 6.09 +/- 7.95, P = 0.042) were lower and higher than control values, even after correction for heart rate (P = 0.03). On the other hand, IMT values were significantly higher in controls than in athletes (c-IMT, P < 0.0001; f-IMT, P < 0.0001). A positive significant correlation between HR and c-IMT and f-IMT (r = 0.527, P < 0.001 and r = 0.539, P < 0.0001, respectively) and between HR and c-PWv (r = 0.410, P = 0.01) was found when controls and athletes were considered as a whole group. Soccer players showed lower PAT values in comparison with controls (P = 0.002). CONCLUSION: Elite sports positively affect c-IMT, f-IMT, and carotid PWv and AIX but not femoral PWv, AIX, AIXr, or PAT. CLINICAL RELEVANCE: Physical activity affects vascular beds in elite athletes differentially, depending on the rate of superior or inferior limb involvement in different sports. In soccer players, physical activity has a protective effect on carotid and femoral vessel walls but worsens femoral arterial and endothelial function. These findings highlight how different results can be shown on carotid and femoral districts, when these vascular districts are differently stressed during sport activity. PMID- 26137180 TI - Balance Error Scoring System Performance in Children and Adolescents With No History of Concussion. AB - BACKGROUND: The Balance Error Scoring System (BESS) is a useful means of measuring postural stability, which frequently exhibits deficits after a concussion. However, it has limited applicability for children since there is insufficient normative data available for the BESS in the pediatric population. The purposes of this study were to report scores for the BESS in children 10 to 17 years old with no history of concussion and to identify whether BESS score is correlated with age, sex, sports participation, height, weight, or body mass index. HYPOTHESIS: Baseline BESS scores will be related to age and sports participation. STUDY DESIGN: Descriptive laboratory study. LEVEL OF EVIDENCE: Level 3. METHODS: One examiner recruited 100 participants 10 to 17 years old over a period of 4 months; performed all of the BESS tests; surveyed participants regarding age, sex, and sports participation; recorded participants' heights and weights; and calculated body mass indices. Intrarater reliability was measured. The main outcome measures were total, firm, and foam surface BESS scores. We assessed data for normality using the Shapiro-Wilk test and used the Spearman rank test to determine whether BESS scores correlated with sex, age, sports participation, height, weight, or body mass index. RESULTS: There was no correlation between the BESS firm surface (5.37 +/- 4.4), BESS foam surface (12.28 +/- 4.43), or total surface scores (17.64 +/- 7.52) and age, anthropometrics, or sports participation. Male and female subjects had similar scores except in the 10- to 13-year-old age group on the foam surface, where girls performed better than boys (10.42 +/- 4.53 vs 13.07 +/- 4.23; P = 0.02). CONCLUSION: Baseline BESS scores in children aged 10 to 17 years were normally distributed and were not related to age, sex, height, weight, body mass index, or sports participation. CLINICAL RELEVANCE: These results provide a reference for clinicians using BESS to evaluate and manage children and teens with concussions. PMID- 26137182 TI - Baker's Cyst: Diagnostic and Surgical Considerations. AB - CONTEXT: Popliteal synovial cysts, also known as Baker's cysts, are commonly found in association with intra-articular knee disorders, such as osteoarthritis and meniscus tears. Histologically, the cyst walls resemble synovial tissue with fibrosis evident, and there may be chronic nonspecific inflammation present. Osteocartilaginous loose bodies may also be found within the cyst, even if they are not seen in the knee joint. Baker's cysts can be a source of posterior knee pain that persists despite surgical treatment of the intra-articular lesion, and they are routinely discovered on magnetic resonance imaging scans of the symptomatic knee. Symptoms related to a popliteal cyst origin are infrequent and may be related to size. EVIDENCE ACQUISITION: A PubMed search was conducted with keywords related to the history, diagnosis, and treatment of Baker's cysts namely, Baker's cyst, popliteal cyst, diagnosis, treatment, formation of popliteal cyst, surgical indications, and complications. Bibliographies from these references were also reviewed to identify related and pertinent literature. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Baker's cysts are commonly found associated with intra-articular knee disorders. Proper diagnosis, examination, and treatment are paramount in alleviating the pain and discomfort associated with Baker's cysts. CONCLUSION: A capsular opening to the semimembranosus-medial head gastrocnemius bursa is a commonly found normal anatomic variant. It is thought that this can lead to the formation of a popliteal cyst in the presence of chronic knee effusions as a result of intra articular pathology. Management of symptomatic popliteal cysts is conservative. The intra-articular pathology should be first addressed by arthroscopy. If surgical excision later becomes necessary, a limited posteromedial approach is often employed. Other treatments, such as arthroscopic debridement and closure of the valvular mechanism, are not well studied and cannot yet be recommended. PMID- 26137181 TI - The Hyperflexible Hip: Managing Hip Pain in the Dancer and Gymnast. AB - CONTEXT: Dance, gymnastics, figure skating, and competitive cheerleading require a high degree of hip range of motion. Athletes who participate in these sports use their hips in a mechanically complex manner. EVIDENCE ACQUISITION: A search of the entire PubMed database (through December 2013) and additional searches of the reference lists of pertinent articles. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 3. RESULTS: Whether innate or acquired, dancers and gymnasts have some hypermobility that allows their hips to be placed in potentially impinging or unstable positions required for their given activity. Such extremes of motion can result in both intra-articular and extra-articular impingement as well as compensatory osseous and muscular pathology. In addition, dancers and gymnasts are susceptible to impingement-induced instability. Dancers with innate generalized hyperlaxity are at increased risk of injury because of their activities and may require longer recovery times to return to play. Both nonoperative and operative treatments (arthroscopic and open) have an important role in returning flexibility athletes to their preoperative levels of sport and dance. CONCLUSION: Because of the extreme hip motion required and the compensatory soft tissue laxity in dancers and gymnasts, these athletes may develop instability, impingement, or combinations of both. This frequently occurs in the setting of subtle pathoanatomy or in patients with normal bony anatomy. With appropriate surgical indications and the correct operative technique, the treating surgeon can anticipate high levels of return to play for the gymnast and dancer with hip pain. PMID- 26137183 TI - Soccer-Related Injuries in Children and Adults Aged 5 to 49 Years in US Emergency Departments From 2000 to 2012. AB - BACKGROUND: An increase in soccer-related injuries occurred in the United States between 2000 and 2012; however, most studies of soccer-related injuries have only examined the pediatric population and not adults. HYPOTHESIS: The number of soccer injuries is increasing in both the pediatric and adult populations. There are differences in injury types and counts when comparing male and female players within various age groups. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 4. METHODS: This retrospective analysis surveyed the US Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) database from 2000 to 2012 for soccer-related injuries in children and adults aged 5 to 49 years. RESULTS: From 2000 to 2012, there were an estimated 2,472,066 soccer-related injuries among 5- to 49-year-olds; 629,994 (25.5%) in adults (aged 20-49 years). The overall estimated pediatric injury count increased significantly over the time period (R (2) = 0.764, P < 0.001). In the 20- to 49 year age range, there was also a significant increase in the estimated number of injuries over the 13-year period, from 41,292 injuries in 2000 to 55,743 in 2012 (R (2) = 0.719, P < 0.001). The estimated injury counts for male players were significantly higher than female players in any given year for all age groups (P < 0.001). Girls aged 5 to 19 years were more likely to have lower extremity injuries than boys (odds ratio [OR], 1.256; 95% CI, 1.214-1.299; P < 0.001). The most common injuries reported were strain/sprains (33.3%), fractures (23.7%), and contusions and abrasions (17.4%) within the 5- to 49-year age category. In both sexes, strains and sprains were significantly lower among 5- to 19-year-olds in comparison with 20- to 49-year-olds (OR, 0.740; 95% CI, 0.714-0.766; P < 0.001). CONCLUSION: There are age- and sex-related differences in estimated injury count, body part injured, type of injury, and hospital admissions for soccer. Also, estimated injury count increased over the 2000 to 2012 time period. CLINICAL RELEVANCE: This study demonstrates that there are differences between pediatric and adult injuries, based on sex, body part, type of injury, and hospital admissions. PMID- 26137185 TI - Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-alpha, and IL-1beta. AB - This study aims to evaluate the effects of diets deficient in choline and/or cystine on hepatocellular injury in animal models (young male Wistar rats, aged 21 days), by monitoring some of the oxidative stress biomarkers and the expression of RAGE, TNF-alpha, and IL-1beta. The animals were divided into 6 groups (n = 10) and submitted to different diets over 30 days: AIN-93 diet (standard, St), AIN-93 choline deficient (CD) diet and AIN-93 choline and cystine deficient (CCD) diet, in the pellet (pl) and powder (pw) diet forms. Independently of the diet form, AIN-93 diet already led to hepatic steatosis and CD/CCD diets provoked hepatic damage. The increase of lipid peroxidation, represented by the evaluation of thiobarbituric acid reactive species, associated with the decrease of levels of antioxidant enzymes, were the parameters with higher significance toward redox profile in this model of hepatic injury. Regarding inflammation, in relation to TNF-alpha, higher levels were evidenced in CD(pl), while, for IL-1beta, no significant alteration was detected. RAGE expression was practically the same in all groups, with exception of CCD(pw) versus CCD(pl). These results together confirm that AIN-93 causes hepatic steatosis and choline and/or cysteine deficiencies produce important hepatic injury associated with oxidative stress and inflammatory profiles. PMID- 26137187 TI - Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats. AB - We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis. PMID- 26137186 TI - High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage. AB - Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl)-2-oxoethyl]-1,2-dimethyl-1H 3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury. PMID- 26137188 TI - MicroRNA-208a Silencing Attenuates Doxorubicin Induced Myocyte Apoptosis and Cardiac Dysfunction. AB - AIMS: GATA4 depletion is a distinct mechanism by which doxorubicin leads to cardiomyocyte apoptosis, and preservation of GATA4 mitigates doxorubicin induced myocyte apoptosis and cardiac dysfunction. We investigated a novel approach of attenuating doxorubicin induced cardiac toxicity by silencing miR-208a, a heart specific microRNA known to target GATA4. METHODS AND RESULTS: Eight-week-old female Balb/C mice were randomly assigned to sham, antagomir, and control groups. Antagomir group were pretreated with miR-208a antagomir 4 days before doxorubicin administration. At day 0, control and antagomir groups received 20 mg/kg of doxorubicin, while sham mice received phosphate buffered solution. Echocardiography was done at day 7, after which animals were sacrificed and hearts harvested and assessed for apoptosis and expression of miR-208a, GATA4, and BCL-2. Doxorubicin significantly upregulated miR-208a, downregulated GATA4, and increased myocyte apoptosis, with resulting decrease in cardiac function. In contrast, therapeutic silencing of miR-208a salvaged GATA4 and BCL-2 and decreased apoptosis, with improvement in cardiac function. CONCLUSION: Doxorubicin upregulates miR-208a and promotes cardiomyocyte apoptosis, while therapeutic silencing of miR-208a attenuates doxorubicin induced myocyte apoptosis with subsequent improvement in cardiac function. These novel results highlight the therapeutic potential of targeting miR-208a to prevent doxorubicin cardiotoxicity. PMID- 26137189 TI - Experiences of health professionals with nutritional support of critically ill patients in tertiary hospitals in Malawi. AB - BACKGROUND: Nutritional support is a recognized determinant of outcome in critically ill patients. Development of critical care services in low-income countries has not been accompanied by certain appropriate ancillary services and interventions, such as adequate nutritional support. This study was designed to investigate the experiences of health professionals who have provided nutritional supportive care to critically ill patients admitted to two major central hospitals in Malawi, with the aim of identifying the common practices in nutritional support in these settings. MATERIALS AND METHODS: A cross-sectional study in which 50 health professionals working in intensive care and high dependency units, admitting both adult and pediatric patients, were interviewed using a semi-structured questionnaire. Data were coded and then analyzed using SPSS version 16.0. Responses between the two hospitals were compared using Fisher's exact test. RESULTS: There was no difference in the composition of respondents from the two hospitals. About 60% of respondents had had experience with nutritional supplementation in their patients-mainly enteral. The most commonly used formulations were the "ready-to-use therapeutic feeds," followed by modified milk. A high percentage of respondents (40%) reported having used dextrose solution as the sole nutritional supplement. Lack of in-service training, nonexistent nutrition protocols pertaining to acutely and critically ill patients, and a lack of clinical nutritionists were the major challenges identified. CONCLUSION: Knowledge of nutrient supplementation was poor among the respondents. The use of ready-to-use therapeutic feeds was quite common, although there is no evidence of its effectiveness in care of acutely critically ill patients. There is a need to establish nutritional support teams in these tertiary hospitals. Clinical nutritionists would ideally help train and play leadership roles in such teams, who would be responsible for assessing patients for their nutritional needs, and ensuring that the feeds provided to patients are appropriate and adequate for their needs. PMID- 26137190 TI - Aerobic endurance in HIV-positive young adults and HIV-negative controls in Malawi. AB - BACKGROUND: Aerobic endurance is an important aspect of physical fitness that enables individuals living with HIV to endure in the work place as well as in agricultural operations in order to earn a living and improve their quality of life. However, despite high HIV prevalence rates, the aerobic endurance status of young Malawians living with HIV remains unknown. The objective of this study was to determine the difference in VO2max between HIV-negative and HIV-positive individuals in Blantyre, Malawi. METHODS: Fifty five participants (17 males and 38 females) who have HIV and were not taking antiretroviral medication and 78 HIV negative participants (45 males and 33 females) performed the Rockport submaximal treadmill exercise test. Measures of body weight, post-exercise heart rate and time to walk one mile were obtained and used to predict VO2max. Comparisons between groups were adjusted for age differences using analysis of covariance (ANCOVA). RESULTS: VO2max was significantly lower in HIV-positive subjects [31.1, 28.7 - 33.5mL.kg-1.min-1(mean, 95% CI)] compared with HIV-negative subjects [56.2, 54.3 - 58.1mL.kg-1.min-1]. CONCLUSION: Aerobic endurance was markedly reduced in HIV-positive participants compared with HIV-negative participants. Findings of the current study implicate factors associated with the HIV infection as contributors to a decreased aerobic endurance in people living with HIV. PMID- 26137192 TI - The Implication of Using NVivo Software in Qualitative Data Analysis: Evidence Based Reflections. AB - For a long time, electronic data analysis has been associated with quantitative methods. However, Computer Assisted Qualitative Data Analysis Software (CAQDAS) are increasingly being developed. Although the CAQDAS has been there for decades, very few qualitative health researchers report using it. This may be due to the difficulties that one has to go through to master the software and the misconceptions that are associated with using CAQDAS. While the issue of mastering CAQDAS has received ample attention, little has been done to address the misconceptions associated with CAQDAS. In this paper, the author reflects on his experience of interacting with one of the popular CAQDAS (NVivo) in order to provide evidence-based implications of using the software. The key message is that unlike statistical software, the main function of CAQDAS is not to analyse data but rather to aid the analysis process, which the researcher must always remain in control of. In other words, researchers must equally know that no software can analyse qualitative data. CAQDAS are basically data management packages, which support the researcher during analysis. PMID- 26137191 TI - Pathologically confirmed breast cancer in Malawi: a descriptive study: Clinical profile of breast cancer. AB - BACKGROUND: Breast cancer is the most common female cancer in Africa, yet no published studies have investigated breast cancer in Malawi. Understanding the clinical profile of breast cancer is important to develop early diagnosis efforts. AIM: To describe clinical and pathological characteristics of breast specimens from a pathology laboratory at a national teaching hospital. METHODS: Secondary analysis of pathology reports from July 2011 to September 2013. RESULTS: Among 85 breast cancer cases, 55% were < 50 years. Median tumor size was 4 cm and 49% were grade 3. Median symptom duration was eight months. CONCLUSIONS: Malawian women with breast cancer commonly have long symptom durations prior to diagnosis, young age, and poorly differentiated tumors. Improved clinical and pathological characterization, including hormone receptor status, are urgently needed to better understand this disease in Malawi. PMID- 26137193 TI - Predictors of maternal mortality among critically ill obstetric patients. AB - AIM: Evaluation of the predictors of maternal mortality among critically ill obstetric patients managed at the intensive care unit (ICU). METHODS: A case control study to evaluate the predictors of maternal mortality among critically ill obstetric patients managed at the intensive care unit (ICU) of the University of Ilorin Teaching Hospital, Ilorin, Nigeria from 1st January 2010 to 30th June 2013. Participants were critically ill obstetric patients who were admitted and managed at the ICU during the study period. Subjects were those who died while controls were age and parity matched survivors. Statistical analysis was with SPSS-20 to determine chi square, Cox-regression and odds ratio; p value < 0.05 was significant. RESULTS: The mean age of subjects and controls were 28.92 +/- 5.09 versus 29.44 +/- 5.74 (p = 0.736), the level of education was higher among controls (p = 0.048) while more subjects were of low social class (p = 0.321), did not have antenatal care (p = 0.131) and had partners with lower level of education (p = 0.156) compared to controls. The two leading indications for admission among subjects and controls were massive postpartum haemorrhage and severe preeclampsia or eclampsia. The mean duration of admission was higher among controls (3.32 +/- 2.46 versus 3.00 +/- 2.58; p = 0.656) while the mean cost of ICU care was higher among the subjects (p = 0.472). The statistical significant predictors of maternal deaths were the patient's level of education, Glasgow Coma Scale (GCS) score, oxygen saturation, multiple organ failure at ICU admission and the need for mechanical ventilation or inotrophic drugs after admission. CONCLUSION: The clinical state at ICU admission of the critically ill obstetric patients is the major outcome determinant. Therefore, early recognition of the need for ICU care, adequate pre-ICU admission supportive care and prompt transfer will improve the outcome. PMID- 26137194 TI - Risk Factors for Neonatal Sepsis and Method for Reduction of Blood Culture Contamination. AB - BACKGROUND: False-positive blood cultures findings may lead to a falsely increased morbidity and increased hospital costs. METHOD: The survey was conducted as retrospective - prospective study and included 239 preterm infants (born before 37 weeks of gestation) who were treated in Neonatal Intensive Care Unit (NICU) in Institute for Child and Youth Health Care of Vojvodina during one year (January 1st, 2012 to December 31st, 2012). The retrospective part of the study focused on examination of incidence of neonatal sepsis and determination of risk factors. In the prospective part of the study infants were sub-divided into two groups: Group 1- infants hospitalized in NICU during the first 6 months of the study; blood cultures were taken by the "clean technique" and checklists for this procedure were not taken. Group 2- neonates hospitalized in NICU during last 6 months of the study; blood cultures were taken by "sterile technique" and checklists for this procedure were taken. RESULTS: The main risk factors for sepsis were prelabor rupture of membranes, low gestational age, low birth weight, mechanical ventilation, umbilical venous catheter placement, and abdominal drainage. Staphylococcus aureus and coagulase negative Staphylococcus were the most frequently isolated microorganisms in false-positive blood samples. CONCLUSIONS: Education of employees, use of checklists and sterile sets for blood sampling, permanent control of false positive blood cultures, as well as regular and routine monthly reports are crucial for successful reduction of contamination rates. PMID- 26137195 TI - Factors contributing to defaulting scheduled therapy sessions by caregivers of children with congenital disabilities. AB - BACKGROUND: Defaulting scheduled rehabilitation therapy may result in increased adverse outcomes such as permanent disability and increased healthcare costs. Concomitantly, there is evidence to suggest that early and continued rehabilitation of children with congenital disabilities can improve outcomes significantly. This study was conducted to determine factors contributing to caregivers' defaulting scheduled rehabilitation therapy sessions. METHODS: A descriptive cross sectional study was carried out at Chitungwiza Central Hospital, a tertiary facility offering in and outpatient rehabilitation services in Zimbabwe. Caregivers of children who had congenital disabilities (N=40) and who had a history of defaulting treatment but were available during the data collection period responded to an interviewer administered questionnaire. Data were analysed for means and frequencies using STATA 13. RESULTS: Factors that contributed to caregivers defaulting scheduled therapy included economic constraints (52%), child related factors (43%), caregiver related factors (42%), service centred factors (30%) and psychosocial factors(58%). Majority of the caregivers (98%) were motivated to attend therapy by observable improvements in their children. Other motivators were incentives given in the rehabilitation department (45%), availability of rehabilitation personnel to provide the required services (48%) and psychosocial support from fellow caregivers, families and the rehabilitation staff (68%). Although all the caregivers could not distinguish occupational therapy from physiotherapy services they all reported that therapy was important. CONCLUSIONS: A combination of psychosocial, economic, child centred and service centred factors contributed to caregivers defaulting scheduled therapy. Interventions that may potentially improve caregiver attendance to scheduled therapy include community outreach services, efficient rehabilitation service provision at the hospitals, and facilitation of income generating programmes for caregivers. PMID- 26137196 TI - The changing role of the primary school teacher in Swaziland in the context of HIV/AIDS: teacher as caretaker and economic provider. AB - Swaziland has the world's highest HIV prevalence with 26% of adults aged 15-49 years living with HIV. There are approximately 17,000 Swazi children aged 0 to 14 years living with HIV. This qualitative study explored the experiences of Swazi teachers supporting learners living with or affected by HIV/AIDS, with a specific focus on the extent to which teachers are aware of the "Rights of the Child" in their teaching and approaches. Important themes emerged from thematic analysis including the following: teachers provided more than education to learners living with and affected by HIV, including material goods and additional time, in some cases at the expense of other learners. In the era of HIV/AIDS, the teacher has become the emotional caretaker and economic provider in addition to the predictable role of educator in Swaziland. Education curricula in HIV-burdened countries need to modify training programmes and support services available to teachers to accommodate the complex role that teachers play in caring for learners living with and affected by HIV. PMID- 26137197 TI - The importance of Leadership towards universal health coverage in Low Income Countries. AB - Universal health coverage--defined as access to the full range of the most appropriate health care and technology for all people at the lowest possible price or with social health protection--was the goal of the 1978 Alma-Ata Conference on Primary Health Care in Kazakhstan. Many low-income (developing) countries are currently unable to reach this goal despite having articulated the same in their health-related documents. In this paper we argue that, over 30 years on, inadequate political and technical leadership has prevented the realization of universal health coverage in low-income countries. PMID- 26137198 TI - Positive outcome of medical leeches (hirudotherapy) for venous congestion. PMID- 26137200 TI - Ultrastructural analyses in the hippocampus CA1 field in Shank3-deficient mice. AB - BACKGROUND: The genetics of autism spectrum disorder (hereafter referred to as "autism") are rapidly unfolding, with a significant increase in the identification of genes implicated in the disorder. Many of these genes are part of a complex landscape of genetic variants that are thought to act together to cause the behavioral phenotype associated with autism. One of the few single locus causes of autism involves a mutation in the SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene. Previous electrophysiological studies in mice with Shank3 mutations demonstrated impairment in synaptic long-term potentiation, suggesting a potential disruption at the synapse. METHODS: To understand how variants in SHANK3 would lead to such impairments and manifest in the brain of patients with autism, we assessed the presence of synaptic pathology in Shank3 deficient mice at 5 weeks and 3 months of age, focusing on the stratum radiatum of the CA1 field. This study analyzed both Shank3 heterozygous and homozygous mice using an electron microscopy approach to determine whether there is a morphological correlate to the synaptic functional impairment. RESULTS: As both synaptic strength and plasticity are affected in Shank3-deficient mice, we hypothesized that there would be a reduction in synapse density, postsynaptic density length, and perforated synapse density. No differences were found in most parameters assessed. However, Shank3 heterozygotes had significantly higher numbers of perforated synapses at 5 weeks compared to 3 months of age and significantly higher numbers of perforated synapses compared to 5-week-old wildtype and Shank3 homozygous mice. CONCLUSIONS: Although this finding represents preliminary evidence for ultrastructural alterations, it suggests that while major structural changes seem to be compensated for in Shank3-deficient mice, more subtle morphological alterations, affecting synaptic structure, may take place in an age-dependent manner. PMID- 26137201 TI - Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura. AB - OBJECTIVES: Malignant hypertension can cause thrombotic microangiopathy (TMA) and the overall presentation may mimic thrombotic thrombocytopenic purpura (TTP). This presents a dilemma of whether or not to initiate plasma exchange. The objective of the study was to determine the clinical and laboratory manifestations of malignant hypertension-induced TMA, and its outcomes. METHODS: Using several search terms, we reviewed English language articles on malignant hypertension-induced TMA, indexed in MEDLINE by 31 December 2013. We also report a new case. All these cases were analyzed using descriptive statistics. RESULTS: A total of 19 patients, with 10 males, had a median age of 38 years at diagnosis; 58% had a history of hypertension. Mean arterial pressure at presentation was 159 mmHg (range 123-190 mmHg). All had prominent renal dysfunction (mean creatinine of 5.2 mg/dl, range 1.7-13 mg/dl) but relatively modest thrombocytopenia (mean platelet count of 60 * 103/ul, range 12-131 * 10(3)/ul). Reported cases (n = 9) mostly had preserved ADAMTS-13 activity (mean 64%, range 18-96%). Following blood pressure control, the majority had improvement in presenting symptoms (100%) and platelet counts (84%); however, only 58% had significant improvement in creatinine. More than half (53%) needed hemodialysis. One patient died of cardiac arrest during pacemaker insertion. CONCLUSION: Prior history of hypertension, high mean arterial pressure, significant renal impairment but relatively modest thrombocytopenia and lack of severe ADAMTS-13 deficiency (activity <10%) at diagnosis are clues to diagnose malignant hypertension-induced TMA. Patients with malignant hypertension respond well to antihypertensive agents and have favorable nonrenal outcomes. PMID- 26137199 TI - Combining metagenomics, metatranscriptomics and viromics to explore novel microbial interactions: towards a systems-level understanding of human microbiome. AB - The advances in experimental methods and the development of high performance bioinformatic tools have substantially improved our understanding of microbial communities associated with human niches. Many studies have documented that changes in microbial abundance and composition of the human microbiome is associated with human health and diseased state. The majority of research on human microbiome is typically focused in the analysis of one level of biological information, i.e., metagenomics or metatranscriptomics. In this review, we describe some of the different experimental and bioinformatic strategies applied to analyze the 16S rRNA gene profiling and shotgun sequencing data of the human microbiome. We also discuss how some of the recent insights in the combination of metagenomics, metatranscriptomics and viromics can provide more detailed description on the interactions between microorganisms and viruses in oral and gut microbiomes. Recent studies on viromics have begun to gain importance due to the potential involvement of viruses in microbial dysbiosis. In addition, metatranscriptomic combined with metagenomic analysis have shown that a substantial fraction of microbial transcripts can be differentially regulated relative to their microbial genomic abundances. Thus, understanding the molecular interactions in the microbiome using the combination of metagenomics, metatranscriptomics and viromics is one of the main challenges towards a system level understanding of human microbiome. PMID- 26137202 TI - Epigenetic regulators as promising therapeutic targets in acute myeloid leukemia. AB - Acute myeloid leukemia (AML), the most prevalent acute leukemia in adults, is an aggressive hematological malignancy arising in hematopoietic stem and progenitor cells. With the exception of a few specific AML subtypes, the mainstays of treatment have not significantly changed over the last 20 years, and are still based on standard cytotoxic chemotherapy. As a result, clinical outcome remains poor for the majority of patients, with overall long-term survival in the region of 20-30%. Recent successes in characterizing the genetic landscape of AML have highlighted that, despite its heterogeneity, many cases of AML carry recurrent mutations in genes encoding epigenetic regulators. Transcriptional dysregulation and altered epigenetic function have therefore emerged as exciting areas in AML research and it is becoming increasingly clear that epigenetic dysfunction is central to leukemogenesis in AML. This has subsequently paved the way for the development of epigenetically targeted therapies. In this review, we will discuss the most recent advances in our understanding of the role of epigenetic dysregulation in AML pathobiology. We will particularly focus on those altered epigenetic programs that have been shown to be central to the development and maintenance of AML in preclinical models. We will discuss the recent development of therapeutics specifically targeting these key epigenetic programs in AML, describe their mechanism of action and present their current clinical development. Finally, we will discuss the opportunities presented by epigenetically targeted therapy in AML and will highlight future challenges ahead for the AML community, to ensure that these novel therapeutics are optimally translated into clinical practice and result in clinical improvement for AML patients. PMID- 26137203 TI - Daratumumab and its potential in the treatment of multiple myeloma: overview of the preclinical and clinical development. AB - Despite the recent major advancement in therapy for multiple myeloma, it remains an incurable disease. There remains an unmet need for novel therapies that target different mechanisms of action. Immunotherapy with monoclonal antibodies is a promising area of development and will expand our therapeutic armamentarium in the fight against myeloma. Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity. It has a favorable safety profile as monotherapy in patients with relapsed/refractory myeloma and also demonstrates significant single-agent activity. Abundant preclinical data supports its use in combination therapy and clinical studies on various exciting combinations are underway. This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab. PMID- 26137204 TI - Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence. AB - Post-translational modifications of the nucleosomal histone proteins orchestrate chromatin organization and gene expression in normal and cancer cells. Among them, the acetylation of N-terminal histone tails represents the fundamental epigenetic mark of open structure chromatin and active gene transcription. The bromodomain and extra-terminal (BET) proteins are epigenetic readers which utilize tandem bromodomains (BRD) modules to recognize and dock themselves on the acetylated lysine tails. The BET proteins act as scaffolds for the recruitment of transcription factors and chromatin organizers required in transcription initiation and elongation. The recent discovery of small molecules capable of blocking their lysine-binding pocket is the first paradigm of successful pharmacological inhibition of epigenetic readers. JQ1 is a prototype benzodiazepine molecule and a specific BET inhibitor with antineoplastic activity both in solid tumours and haematological malignancies. The quinolone I-BET151 and the suitable for clinical development I-BET762 benzodiazepine were introduced in parallel with JQ1 and have also shown potent antitumour activity in preclinical studies. I-BET762 is currently being tested in early phase clinical trials, along with a rapidly growing list of other BET inhibitors. Unlike older epigenetic therapies, the study of BET inhibitors has offered substantial, context-specific, mechanistic insights of their antitumour activity, which will facilitate optimal therapeutic targeting in future. Here, we review the development of this novel class of epigenetic drugs, the biology of BET protein inhibition, the emerging evidence from preclinical work and early phase clinical studies and we discuss their potential role in the treatment of haematological malignancies. PMID- 26137206 TI - Potential for specific dihydropyridine calcium channel blockers to have a positive impact on cognitive function in humans: a systematic review. AB - BACKGROUND: There is some evidence to suggest a possible association between calcium channel blocker (CCB) use and a lower decline in cognitive function compared with use of other hypertensive treatments. In particular, there is an emerging interest in the potential for specific CCBs, particularly the dihydropyridine CCBs nitrendipine, nicardipine, cilnidipine, lercandipine, nimodipine, azelnidipine and nilvadipine. The aim of this review was to assess the evidence relating to these specific CCBs and incident cognitive decline or dementia in humans. METHODS: A systematic review of the literature was carried out. The databases MEDLINE, Embase and PsychINFO were searched from 1980 to 18 April 2014. All abstracts were reviewed by two independent reviewers. RESULTS: From 753 unique records, 16 full text articles were examined and three retained. The three articles reported data from two studies. A 12-week double-blind randomized controlled trial of nitrendipine compared with cilazapril and a longer and larger double-blind placebo-controlled trial also of nitrendipine, namely the Systolic Hypertension in Europe trial (SYST-EUR). Nitrendipine was associated with a reduction in incident dementia in the SYST-EUR trial. There was no association seen for cognitive outcomes in the smaller trial. CONCLUSION: At present there is limited evidence to suggest that nitrendipine may be associated with reduction in incident dementia. This association comes from a single trial and needs to be replicated. Furthermore, there is no high-quality evidence for any of the other potential candidate CCBs. PMID- 26137205 TI - Advances and challenges in the management of essential thrombocythemia. AB - The new World Health Organization (WHO) diagnostic criteria for essential thrombocythemia (ET) issued in 2008 made an important distinction between true ET and early myelofibrosis (MF), which has helped to identify a more homogenous population for the diagnosis with longer survival and much less transformation to overt MF. The recent finding of a new mutation (CALR), which is mutually exclusive with JAK2 and MPL mutations, adds to the characterization of ET patients, since there are important phenotypic differences between the mutation types. CALR patients are younger, have lower white blood cell counts (WBC) and a lower thrombosis incidence. A growing field of interest is the state of hypercoagulation due to dysfunction of hemostatic systems, cell-cell interaction and hereditary prothrombotic traits. Activation of platelets, WBC and endothelial cells has been found, making the whole intravascular milieu prothrombotic. Several risk score models, based on retrospective studies, have been developed lately, distinguishing patient groups with graded risk for complications and death. Even if these may be helpful in evaluating patients, they have not been validated in prospective studies and there are not enough data to support their use as a basis for treatment algorithms. The traditional risk factors age, previous thrombosis and platelets >1500 * 10(9)/l are still recommended for the distinction between high risk and low risk ET and the decision to give cytoreductive therapy. However, cardiovascular (CV) risk factors add to thrombosis risk and should be considered both for specific treatment in any risk group and for upgrading low risk patients with high CV risk to an intermediary group where active therapy with aspirin and cytoreduction may be considered. First-line cytoreductive therapy differs with age; in younger patients interferon (IFN) or anagrelide are preferable, in older patients hydroxycarbamide (HC). Second-line therapy for younger patients is HC, for older patients IFN or anagrelide (ANA). JAK2 inhibitors may be suitable in rare cases with symptoms not responding to other therapy. PMID- 26137207 TI - Bedaquiline for the treatment of multidrug-resistant tuberculosis: great promise or disappointment? AB - Acquired drug resistance by Mycobacterium tuberculosis (MTB) may result in treatment failure and death. Bedaquiline was recently approved for the treatment of multidrug-resistant tuberculosis (MDR-TB). This report examines the available data on this novel drug for the treatment of MDR-TB. PubMed searches, last updated 18 February 2015, using the terms bedaquiline, TMC 207 and R207910 identified pertinent English citations. Citation reference lists were reviewed to identify other relevant reports. Pertinent MDR-TB treatment reports on the US Food and Drug Administration, Centers for Disease Control and Prevention (CDC), World Health Organization (WHO) and Cochrane websites were also evaluated. Bedaquiline is an adenosine triphosphate (ATP) synthase inhibitor specific for MTB and some nontuberculous mycobacteria. The early bactericidal activity (EBA) of bedaquiline is delayed until ATP stores are depleted but subsequently it is similar to the EBA of isoniazid and rifampin. Bedaquiline demonstrated excellent minimum inhibitory concentrations (MICs) against both drug-sensitive and MDR-TB. Adding it to the WHO-recommended MDR-TB regimen reduced the time for sputum culture conversion in pulmonary MDR-TB. Rifampin, other cytochrome oxidase 3A4 inducers or inhibitors alter its metabolism. Adverse effects are common with MDR TB treatment regimens with or without bedaquiline. Nausea is more common with bedaquiline and it increases the QTcF interval. It is not recommended for children, pregnant or lactating women. More patients died in the bedaquiline treatment arms despite better microbiological outcomes in two recent trials. The WHO and CDC published interim guidelines that recommend restricting its use to patients with MDR-TB or more complex drug resistance who cannot otherwise be treated with a minimum of three effective drugs. It should never be added to a regimen as a single drug nor should it be added to a failing regimen to prevent the emergence of bedaquiline-resistant strains. PMID- 26137208 TI - Atypical femoral fractures and bisphosphonate use: current evidence and clinical implications. AB - Osteoporosis is a disease characterized by a low bone volume and deterioration of the bone quality, which increases the risk of low-energy fractures. Bisphosphonate (BP) treatment increases the bone mass and reduces the risk of fractures in patients with osteoporosis by suppressing bone resorption. In spite of its clinical benefits, the long-term use of BPs has been linked to the occurrence of atypical femoral fractures (AFFs). Although the evidence had been controversial regarding the association between the occurrence of AFFs and BP use, more recent studies with radiographic adjudication have indicated the significant associations between them. However, the pathogenesis of AFFs is not completely understood. The most popular hypothesis has suggested that the suppression of bone turnover by BPs is responsible; however, some recent reports have implied the involvement of pathophysiological alterations of the bone quality and fracture repair process. In this review, we summarize and discuss the epidemiology, risk factors and pathology of AFFs. PMID- 26137209 TI - Psoriatic arthritis: latest treatments and their place in therapy. AB - Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease that may affect peripheral and axial joints, entheses, skin and nails, and other organs. Treatment with nonsteroidal anti-inflammatory drugs, steroid and disease modifying antirheumatic drugs had been the backbone of traditional management of PsA for many years. However, improvement in our understanding of immunopathogenesis of PsA has led to new immunomodulatory therapies. Introduction of novel agents has raised the bar for treatment and helped drive research into additional therapeutic options. PMID- 26137211 TI - A case of false mother included with 46 autosomal STR markers. AB - BACKGROUND: For solving a maternity case, 19 autosomal short tandem repeats (STRs) were amplified using the AmpFlSTR((r)) Sinofiler(TM) kit and PowerPlex((r)) 16 System. Additional 27 autosomal STR loci were analyzed using two domestic kits AGCU 21+1 and STRtyper-10G. The combined maternity index (CMI) was calculated to be 3.3 * 10(13), but the putative mother denied that she had given birth to the child. In order to reach an accurate conclusion, further testing of 20 X-chromosomal short tandem repeats (X-STRs), 40 single nucleotide polymorphism (SNP) loci, and mitochondrial DNA (mtDNA) was carried out. FINDINGS: The putative mother and the boy shared at least one allele at all 46 tested autosomal STR loci. But, according to the profile data of 20 X-STR and 40 SNP markers, different genotypes at 13 X-STR loci and five SNP loci excluded maternity. Mitochondrial profiles also clearly excluded the mother as a parent of the son because they have multiple differences. It was finally found that the putative mother is the sister of the biological father. CONCLUSIONS: Different kinds of genetic markers needfully supplement the use of autosomal STR loci in case where the putative parent is suspected to be related to the true parent. PMID- 26137210 TI - P2Y12 antagonists in non-ST-segment elevation acute coronary syndromes: latest evidence and optimal use. AB - Dual antiplatelet therapy (DAPT), which includes the combination of aspirin and a P2Y12 platelet receptor inhibitor, is a well-established antiplatelet regimen in the treatment of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Three P2Y12 inhibitor options (clopidogrel, prasugrel and ticagrelor) are currently available, all having different efficacy and safety profiles along with contrasting contraindications, special warnings and precautions for use. This review compares and contrasts the unique P2Y12 antagonists in the NSTE-ACS setting, covering the latest evidence and their optimal use. PMID- 26137212 TI - Evaluation of pulmonary function changes in children with type 1 diabetes mellitus in Upper Egypt. AB - BACKGROUND: Diabetes mellitus is a leading cause of morbidity and mortality among children across the world and is responsible for a growing proportion of global healthcare expenditure. However, limited data are available on lung dysfunction in children with diabetes. AIM: The aim of this study was to evaluate the pulmonary function changes in children with type 1 diabetes mellitus (T1DM). METHODS: We studied 60 children with T1DM (mean age 10.5 +/- 2.32 years; disease duration 2.45 +/- 0.6 years, and 50 healthy control children (mean age 9.9 +/- 2.5 years). Spirometry was performed for all individuals to measure forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and peak expiratory flow rate (PEFR). Glycemic control was assessed on the basis of glycated hemoglobin (HbA1c), with HbA1c values <8% considered to indicate good glycemic control, and HbA1c values ?8% to indicate poor control. RESULTS: There was significant reduction in all spirometeric parameters in diabetic children in comparison with healthy control children. Children with poor glycemic control had significant impairment in lung functions compared with those with good glycemic control. CONCLUSIONS: T1DM in children leads to impairment of lung functions and this impairment increases with poor glycemic control. PMID- 26137213 TI - Glucuretic effects and renal safety of dapagliflozin in patients with type 2 diabetes. AB - Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor approved as a treatment for type 2 diabetes mellitus (T2DM) in the United States, the European Union and other countries. Dapagliflozin increases renal glucose excretion in an insulin-independent manner, and its mechanism of action is complementary to those of other antidiabetes medications. When used as monotherapy or in combination with other oral antidiabetes medications or insulin, dapagliflozin improves glycemic measures in patients with T2DM. Dapagliflozin treatment is also associated with weight reduction and a decrease in blood pressure, both of which may be beneficial in patients with T2DM. Because of its mechanism of action, dapagliflozin has a low intrinsic propensity to cause hypoglycemia. Overall, dapagliflozin is well tolerated, with the frequency of most adverse events similar to that seen with placebo. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in dapagliflozin-treated groups compared with placebo groups. In the clinical development program, more cases of newly diagnosed bladder cancer were reported for patients treated with dapagliflozin (0.17%) compared with placebo or comparator (0.03%). Although there were not enough cases to determine causality, dapagliflozin should not be used in patients with bladder cancer and should be used with caution in patients with a history of bladder cancer. Dapagliflozin may decrease glomerular filtration rate (GFR), especially in elderly patients and patients with impaired renal function. Renal function should be monitored before initiation of dapagliflozin. Dapagliflozin should not be used in patients with an estimated GFR <60 ml/min/1.73 m(2). No cardiovascular safety signals have been detected for dapagliflozin, and a long-term cardiovascular outcomes study is ongoing. Evidence from clinical trials suggests that dapagliflozin is a promising new treatment option for T2DM. PMID- 26137214 TI - The role of adipokines in gestational diabetes mellitus. AB - Gestational diabetes mellitus (GDM) is a complication of pregnancy that is characterized by impaired glucose tolerance with onset or first recognition during pregnancy. The reported prevalence of GDM varies between 0.6% and 20% of pregnancies depending on screening method, gestational age and the population studied. GDM is characterized by pancreatic beta-cell function that is insufficient to meet the body's insulin needs. Available evidence suggests that beta-cell defects in GDM result from the same spectrum of causes that underline hyperglycemia in general, including autoimmune disease, monogenic causes and insulin resistance. Adipokines are proteins secreted from the adipocytes and are believed to have a metabolic influence. Our review suggests that, in GDM, various adipokines, mainly leptin and adiponectin, are dysregulated. These two adipokines might have both prognostic and pathophysiological significance in this disease. PMID- 26137215 TI - Glucagon-like polypeptide agonists in type 2 diabetes mellitus: efficacy and tolerability, a balance. AB - Glucagon-like polypeptide (GLP-1) receptor agonist treatment has multiple effects on glucose metabolism, supports the beta cell, and promotes weight loss. There are now five GLP-1 agonists in clinical use with more in development. GLP-1 treatment typically can induce a lowering of hemoglobin A1c (HbA1c) of 0.5-1.5% over time with weight loss of 2-5%. In some individuals, a progressive loss of weight occurs. There is evidence that GLP-1 therapy opposes the loss of beta cells which is a feature of type 2 diabetes. The chief downside of GLP-1 treatment is the gastrointestinal motility disturbance which is one of the modes of action of the hormone; significant nausea, vomiting, and diarrhea may lead to discontinuation of treatment. Although daily injection of GLP-1 agents is successful, the development of extended release preparations allows for injection once weekly, and perhaps much longer in the future. The indication for GLP-1 use is diabetes, but now, liraglutide has been approved for primary treatment of obesity. When oral agents fail to control glucose levels in type 2 diabetes, there is a choice between long-acting insulin and GLP-1 agonists as additional treatments. The lowering of HbA1c by either modality is equivalent in most studies. Patients lose weight with GLP-1 treatment and gain weight on insulin. There is a lower incidence of hypoglycemia with GLP-1 therapy but a much higher incidence of gastrointestinal complaints. Insulin dosing is flexible while GLP-1 agents have historically been administered at fixed dosages. Now, the use of combined long-acting insulin and GLP-1 agonists is promising a major therapeutic change. Combined therapy takes advantage of the benefits of both insulin and GLP 1 agents. Furthermore, direct admixture of both in the same syringe will permit flexible dosing, improvement of glucose levels, and reduction of both hypoglycemia and gastrointestinal side effects. PMID- 26137217 TI - Challenges faced by Arab women who are interested in becoming physicians. AB - Understanding the underlying reasons for the under-representation of Arab women within the health care system in Israel is crucial for creating future strategies for intervention, in order to minimize the gaps in the health care system and thus improve the medical services and health status. Our commentary tries to shed light on the underrepresentation and the marginalization of the Arab women in society in general and in the medical field in specific. PMID- 26137216 TI - Application of CRISPR/Cas9 for biomedical discoveries. AB - The Clustered Regions of Interspersed Palindromic Repeats-Cas9 (CRISPR/Cas9), a viral defense system found in bacteria and archaea, has emerged as a tour de force genome editing tool. The CRISPR/Cas9 system is much easier to customize and optimize because the site selection for DNA cleavage is guided by a short sequence of RNA rather than an engineered protein as in the systems of zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and meganucleases. Although it still suffers from some off-target effects, the CRISPR/Cas9 system has been broadly and successfully applied for biomedical discoveries in a number of areas. In this review, we present a brief history and development of the CRISPR system and focus on the application of this genome editing technology for biomedical discoveries. We then present concise concluding remarks and future directions for this fast moving field. PMID- 26137218 TI - Surface boxplots. AB - In this paper, we introduce a surface boxplot as a tool for visualization and exploratory analysis of samples of images. First, we use the notion of volume depth to order the images viewed as surfaces. In particular, we define the median image. We use an exact and fast algorithm for the ranking of the images. This allows us to detect potential outlying images that often contain interesting features not present in most of the images. Second, we build a graphical tool to visualize the surface boxplot and its various characteristics. A graph and histogram of the volume depth values allow us to identify images of interest. The code is available in the supporting information of this paper. We apply our surface boxplot to a sample of brain images and to a sample of climate model outputs. PMID- 26137219 TI - Nutrition and metabolism in poultry: role of lipids in early diet. AB - Modern strains of broiler chickens are selected for fast growth and are marketed anywhere from 36 to 49 days after a 21-day incubational period. For a viable healthy chick, all the necessary nutrients required for growth and development must be provided by the hen through the fertilized egg. The current feeding strategies for improved growth, health and productivity are targeted towards chicks after hatching. Considering the fact that developing chick embryo spends over 30 % of its total life span inside the hatching egg relying on nutrients deposited by the breeder hen, investigations on nutritional needs during pre hatch period will improve embryonic health, hatchability and chick viability. In this context, investigations on hatching egg lipid quality is of utmost importance because, during incubation, egg fat is the major source of energy and sole source of essential omega-6 (n-6) and omega-3 (n-3) fatty acids to the chick embryo. Due to the unique roles of n-3 and n-6 fatty acids in growth, immune health, and development of central nervous system, this review will focus on the role of early exposure to essential fatty acids through maternal diet and hatching egg and its impact on progeny in meat-type broiler chickens. PMID- 26137220 TI - Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells. AB - BACKGROUND: Pyruvate dehydrogenase (PDH) occupies a central node of intermediary metabolism, converting pyruvate to acetyl-CoA, thus committing carbon derived from glucose to an aerobic fate rather than an anaerobic one. Rapidly proliferating tissues, including human tumors, use PDH to generate energy and macromolecular precursors. However, evidence supports the benefits of constraining maximal PDH activity under certain contexts, including hypoxia and oncogene-induced cell growth. Although PDH is one of the most widely studied enzyme complexes in mammals, its requirement for cell growth is unknown. In this study, we directly addressed whether PDH is required for mammalian cells to proliferate. RESULTS: We genetically suppressed expression of the PDHA1 gene encoding an essential subunit of the PDH complex and characterized the effects on intermediary metabolism and cell proliferation using a combination of stable isotope tracing and growth assays. Surprisingly, rapidly dividing cells tolerated loss of PDH activity without major effects on proliferative rates in complete medium. PDH suppression increased reliance on extracellular lipids, and in some cell lines, reducing lipid availability uncovered a modest growth defect that could be completely reversed by providing exogenous-free fatty acids. PDH suppression also shifted the source of lipogenic acetyl-CoA from glucose to glutamine, and this compensatory pathway required a net reductive isocitrate dehydrogenase (IDH) flux to produce a source of glutamine-derived acetyl-CoA for fatty acids. By deleting the cytosolic isoform of IDH (IDH1), the enhanced contribution of glutamine to the lipogenic acetyl-CoA pool during PDHA1 suppression was eliminated, and growth was modestly suppressed. CONCLUSIONS: Although PDH suppression substantially alters central carbon metabolism, the data indicate that rapid cell proliferation occurs independently of PDH activity. Our findings reveal that this central enzyme is essentially dispensable for growth and proliferation of both primary cells and established cell lines. We also identify the compensatory mechanisms that are activated under PDH deficiency, namely scavenging of extracellular lipids and lipogenic acetyl-CoA production from reductive glutamine metabolism through IDH1. PMID- 26137221 TI - Insights into the origin of DNA methylation differences between monozygotic twins discordant for schizophrenia. AB - BACKGROUND: DNA methylation differences between monozygotic twins discordant for schizophrenia have been previously reported. However, the origin of methylation differences between monozygotic twins discordant for schizophrenia is not clear. The findings here argue that all DNA methylation differences may not necessarily represent the cause of the disease; rather some may result from the effect of antipsychotics. METHODS: Methylation differences in rat brain regions and also in two pairs of unrelated monozygotic twins discordant for schizophrenia have been studied using genome-wide DNA methylation arrays at Arraystar Inc. (Rockville, Maryland, USA). The identified gene promoters showing significant alterations to DNA methylation were then further characterized using ingenuity pathway analysis (Ingenuity System Inc, CA, USA). RESULTS: Pathway analysis of the most significant gene promoter hyper/hypomethylation revealed a significant enrichment of DNA methylation changes in biological networks and pathways directly relevant to neural development and psychiatric disorders. These included HIPPO signaling (p = 3.93E-03) and MAPK signaling (p = 4.27E-03) pathways involving hypermethylated genes in schizophrenia-affected patients as compared to their unaffected co-twins. Also, a number of significant pathways and networks involving genes with hypomethylated gene promoters have been identified. These included CREB signaling in neurons (p = 1.53E-02), Dopamine-DARPP32 feedback in cAMP signaling (p = 7.43E-03) and Ephrin receptors (p = 1.13E-02). Further, there was significant enrichment for pathways involved in nervous system development and function (p = 1.71E-03-4.28E-02). CONCLUSION: The findings highlight the significance of antipsychotic drugs on DNA methylation in schizophrenia patients. The unique pathways affected by DNA methylation in the two pairs of monozygotic twins suggest that patient-specific pathways are responsible for the disease; suggesting that patient-specific treatment strategies may be necessary in treating the disorder. The study reflects the need for developing personalized medicine approaches that take into consideration epigenetic variations between patients. PMID- 26137222 TI - Endocan: A new marker for cancer and a target for cancer therapy. AB - Endocan, previously known as endothelial cell-specific molecule-1 (ESM-1), was cloned from the human umbilical vein endothelial cell cDNA library. Endocan is a novel ESM, and a 50 kDa soluble proteoglycan. Endocan is secreted into the blood as the soluble proteoglycan, which is the form in the presence of chondroitin sulfate. In normal tissues, chondroitin sulfate/dermatan sulfate proteoglycan is expressed by endothelial cells (such as lung and kidney) and is overexpressed in several carcinoma endothelial cells. There are studies that identified high endocan expression in lung cancer, uterine cancer, kidney cancer, liver cancer, brain glioblastoma, breast cancer and other tumors. Tumor prognosis, metastasis and angiogenesis were shown to be associated with endocan expression. The majority of investigators believe that endocan regulates the tumor by tumor associated inflammation, angiogenesis, lymphangiogenesis, the tumor cells themselves and other aspects. Endocan may be a new target for cancer therapy. PMID- 26137223 TI - Analysis of alternatives for insulinizing patients to achieve glycemic control and avoid accompanying risks of hypoglycemia. AB - The aims of the present study were to explore the efficacy of glycemic control and the risks of hypoglycemia with different methods of insulin therapy, and to provide reference data for the clinical treatment of diabetes. In this retrospective study, hospitalized patients diagnosed with type 2 diabetes between March and December 2014, in the Department of Endocrinology in the First Affiliated Hospital of Wannan Medical College, were divided into three groups, including an intensive insulin analogue therapy group, a premixed insulin analogue treatment group and a premixed human insulin therapy group. The efficacy of glycemic control and the incidence of hypoglycemia were determined in each of the insulin treatment groups. Compared with the other treatment groups, the intensive insulin analogue therapy group was associated with superior blood glucose control, shorter time to reach standard insulin regimen, shorter hospitalization time, fewer fluctuations in blood glucose levels and lower insulin dosage on discharge from hospital. However, this treatment was also associated with a high risk of hypoglycemia. In conclusion, when combined with the effective prevention of hypoglycemia and appropriate nursing care (especially in hospital care), intensive insulin analogue therapy may provide the greatest benefit to patients. PMID- 26137224 TI - Effects of high-fat diet on 1,2-dimethylhydrazine-induced aberrant crypt foci and colorectal tumours in rats. AB - Obesity is one of the leading causes of numerous types of cancer. The present study investigated the impact of a high-fat diet on 1,2-dimethylhydrazine (DMH) induced colorectal cancer (CRC) in F344 rats. A total of 16 male F344 rats aged 4 weeks were randomly divided into two groups (8 rats/group). Rats in group A were fed a basal diet with a moderate fat (MF) content, while rats in group B were fed a high-fat diet. Upon reaching 5 weeks of age, the rats were injected subcutaneously with DMH (20 mg/kg body weight). DMH was administered once a week for 8 consecutive weeks. All the rats were sacrificed 34 weeks after the first DMH injection and dissected to obtain samples of colorectal tissues. The tissues were examined under a microscope for the presence of aberrant crypt foci (ACFs) and subjected to histopathological analysis. The results showed that at the end of the 34-week experiment, body weights and visceral fat levels were significantly higher in the high-fat diet group compared to the basal diet group. In addition, the incidences of colorectal ACF, adenoma and adenocarcinoma were markedly elevated in the high-fat diet group compared to the basal diet group. These results indicate that the consumption of a high-fat diet promotes the development and progression of CRC and the control of fat intake may prevent CRC. PMID- 26137225 TI - Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats. AB - The purpose of the present study was to evaluate the combined effects of vitamin K (VK) and teriparatide (TPTD) on bone mineral density (BMD), mechanical strength and other parameters for bone metabolism using a rat ovariectomized osteoporosis model. Ovariectomized female Sprague-Dawley rats were administered with VK (an oral dose of 30 mg/kg/day), TPTD (a subcutaneous dose of 30 ug/kg, three times a week) or a combination for 8 weeks. Thereafter, serum levels of gamma carboxylated osteocalcin (Gla-OC) were quantitated by ELISA; BMD and mechanical strength were measured by computed tomography and biomechanical testing, respectively at the femoral metaphysis. Additionally, histomorphometry was performed using the toluidine blue-stained coronal sections of distal femur. The combination of VK and TPTD clearly increased the serum levels of Gla-OC (a specific marker for bone formation) and osteoblast surface (the number of osteoblasts attaching with the surface of cancellous bone), compared to VK or TPTD alone. In addition, the combination of the two agents improved the BMD and bone strength of the femur in the ovariectomized rats, compared to VK or TPTD alone. Taken together, these findings suggest that the treatment with VK and TPTD may have a therapeutic advantage over VK or TPTD monotherapy for postmenopausal osteoporosis, possibly by enhancing the bone formation through the actions on OC and osteoblasts. PMID- 26137226 TI - Neurocytoma of the pituitary gland: A case report and literature review. AB - Extraventricular neurocytomas (EVN) are rare central nervous system tumors, often located within the cerebral hemisphere. The present study reports a case of a 56 year-old male patient with bitemporal hemianopsia. Computed tomography and magnetic resonance imaging revealed a tumor in the sellar region. The tumor was totally excised. Postoperative histological examination of the tumor demonstrated that synaptophysin, chromogranin-A and neuron-specific enolase were positive, while luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, adrenocorticotropic hormone, thyroid-stimulating hormone, glial fibrillary acidic protein, S-100, nestin and epithelial membrane antigen were negative, which were the main pathological features of neurocytomas. This is the fourth case of EVN located in the sellar region reported. The associated studies are also reviewed. PMID- 26137228 TI - Expression of MALAT1 in the peripheral whole blood of patients with lung cancer. AB - A blood-based biomarker assay is a non-invasive way to screen that can identify lung cancer at an earlier stage to improve the clinical outcome. MALAT1 is a broadly expressed, long non-coding RNA in human tissues and is overexpressed in numerous human carcinomas. The potential of MALAT1 in the whole blood of lung cancer was evaluated. In the present study, blood samples of patients with lung cancer and healthy volunteers (controls) were recruited and analyzed by quantitative polymerase chain reaction (qPCR) for MALAT1 expression and clinicopathological data. Lung cancer tissues were also analyzed by qPCR. The expression of MALAT1 in the whole blood of lung cancer was lower compared to the control. The area under the receiver operator curve was 0.718 (P<0.001). Relatively, the expression of MALAT1 was stronger in the whole blood of lung cancer with metastasis compared to non-metastasis. Additionally, the whole blood with bone or brain metastasis exhibited a higher expression of MALAT1 compared to the blood with lymph node or pleura metastasis. Subsequently, a lower expression of MALAT1 was detected in metastatic lymph node tissues than that of the carcinoma in situ of the lung. Taken together, these results indicate that MALAT1 as a biomarker to screen lung cancer may represent a host response to lung cancer. PMID- 26137227 TI - Comparison of the enzymatic and explant methods for the culture of keratinocytes isolated from human foreskin. AB - Currently, culture and growth keratinocytes are important stages in achieving a reliable and reproducible skin tissue. In the present study, two different methods, enzymatic and explant methods, for keratinocytes isolation from human foreskin were compared. Foreskins were cut into 2-3 mm pieces and placed in trypsin at 4 degrees C overnight for separation of the epidermis from the dermis. Subsequently, these samples were divided into two groups: i) Keratinocytes separated from the epidermis by trypsin and ii) by the explant method. These keratinocytes were divided into two groups: i) With no feeder layer and ii) onto a type I collagen scaffold. The cells were evaluated using immunocytochemistry and 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI) staining. In the enzymatic treatment, after 7-10 days no attached cells were found in the cell culture dishes. In the explant method, keratinocytes were separated after ~24 h, attached rapidly and formed big colonies into a collagen scaffold. In the absence of a feeder layer, small colonies were developed with rapid loss of proliferation within 2-3 days. Keratinocytes showed positive immunoreactivity for the pan cytokeratin marker and keratinocytes' nuclei were clearly observed. This method could be applied and developed as a component of skin substitutes to treat burns and wounds and also in laboratory testing. PMID- 26137229 TI - No association between the ApoE epsilon2 and epsilon4 alleles and the risk of obstructive sleep apnea: A systematic review and meta-analysis. AB - Apolipoprotein E (ApoE) gene epsilon2 and epsilon4 alleles have been reported to be associated with the risk of obstructive sleep apnea (OSA); however, the results are controversial. Thus, we performed a meta-analysis to obtain a more precise estimate of the associations by pooling sporadic, inconsistent and small sample-size studies. Electronic databases such as PubMed and Embase were searched to identify eligible studies focusing on the association between ApoE polymorphisms and susceptibility to OSA before April 2014. The associations were assessed by odds ratio (ORs) with 95% confidence intervals (CIs). The Begg and Egger's test was used to evaluate publication bias. Ten eligible studies (1,696 cases/2,216 controls for the epsilon2 allele and 2,449 cases/5,592 controls for the epsilon4 allele) were included in the meta-analysis. An association between the ApoE epsilon2 and epsilon4 alleles and OSA was not found in the overall population (OR=0.97, 95% CI: 0.75-1.25; OR=1.09, 95% CI: 0.86-0.38 for ApoE epsilon2 and epsilon4, respectively). Significant heterogeneity (epsilon2: I2=36.6%, P=0.16; epsilon4: I2=69.7%, P=0.001) was observed across studies, however, heterogeneity could not be explained by variations in mean age, body mass index, apnea hypopnea index, gender, ethnic background, or the ApoE epsilon2 and epsilon4 alleles. No evidence of publication bias was found according to the Begg and Egger's test. In conclusion, our findings show that the ApoE epsilon2 and epsilon4 alleles have no significant associations with OSA susceptibility based on available data. PMID- 26137230 TI - Association between the polymorphisms of the vascular endothelial growth factor gene and metabolic syndrome. AB - Vascular endothelial growth factor (VEGF) is a major angiogenic factor. Increased levels of VEGF have been reported in patients with metabolic syndrome (MetS). The role of VEGF polymorphisms in MetS susceptibility, however, has not been reported previously. Thus, the present study was performed to analyze the associations between the VEGF -634G>C and 936C>T polymorphisms and the patients with MetS. A total of 320 patients with MetS (mean age, 49.86+/-11.76 years) and 320 healthy subjects (mean age, 50.94+/-8.43 years) were enrolled in the study. The VEGF 634G>C polymorphism in the 5'-untranslated region (UTR) and 936C>T polymorphism in 3'-UTR were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The VEGF -634G>C polymorphism significantly affected MetS susceptibility. The CC genotype of the -634G>C polymorphism was significantly associated with an increased risk of MetS [adjusted odds ratio (AOR)=3.973; 95% confidence interval (CI), 2.321-6.799; P<0.0001]. AORs of the dominant (GG vs. GC+CC) and recessive models (GG+GC vs. CC) between the cases and controls were 2.569 (95% CI, 1.657-3.983; P<0.0001) and 2.163 (95% CI, 1.475-3.171; P=0.0001), respectively. Haplotypes of -634G>C and 936C>T were also associated with MetS susceptibility. When the haplotype data were stratified by gender, the association remained only in males. The -634G>C polymorphism was also associated with the subgroups of MetS risk components by the stratification analysis. The 936C>T polymorphism was, however, not associated with the MetS susceptibility. The present study demonstrates that the VEGF -634G>C polymorphism and haplotypes may be a genetic determinant for the MetS susceptibility. To the best of our knowledge, this is the first study on the significant association of the VEGF polymorphisms in MetS patients. To confirm the effects of the VEGF polymorphisms on MetS, further functional and population studies are required. PMID- 26137231 TI - Association investigation of BACH2 rs3757247 and SOD2 rs4880 polymorphisms with the type 1 diabetes and diabetes long-term complications risk in the Polish population. AB - Genetic factors are indicated in the development of type 1 diabetes (DM1). Recently, nucleotide variants of BACH2 and SOD2 have been associated with this chronic condition. Therefore, the purpose of the present study was to investigate the contribution of BACH2 rs3757247 and SOD2 rs4880 (Ala16Val) polymorphisms to the risk of DM1 and diabetes long-term complications. Selected polymorphic variants of BACH2 and SOD2 were investigated in a group of 141 patients with DM1 and in a group of age, gender-matched healthy subjects (n=369) using a high resolution melting curve method. There was no evidence for either allelic or genotypic association with the risk of DM1 and diabetes chronic complications for analysed polymorphisms. In addition, no interaction between BACH2 and SOD2 variants in the development of this condition was observed. However, the frequency of BACH2 rs3757247 AG and AA genotypes was statistically different between DM1 patients with retinopathy and healthy individuals (odds ratio, 2.455; 95% confidence interval, 0.999-6.035; P=0.044), but this result did not survive multiple testing corrections. The present study did not confirm the involvement of BACH2 rs3757247 and SOD2 rs4880 polymorphisms in the development of DM1 and diabetes long-term complications. Further studies in a larger population sample are required. PMID- 26137232 TI - Cross-talks between microRNAs and mRNAs in pancreatic tissues of streptozotocin induced type 1 diabetic mice. AB - Network cross-talks between microRNAs (miRNAs) and mRNAs may be useful to elucidate the pathological mechanisms of pancreatic islet cells in diabetic individuals. The aim of the present study was to investigate the cross-talks between miRNAs and mRNAs in pancreatic tissues of streptozotocin-induced diabetic mice through microarray and bioinformatic methods. Based on the miRNA microarray, 64 upregulated and 72 downregulated miRNAs were observed in pancreatic tissues in diabetic mice compared to the normal controls. Based on the mRNA microarrray, 507 upregulated mRNAs and 570 downregulated mRNAs were identified in pancreatic tissues in diabetic mice compared to the normal controls. Notably, there were 246 binding points between upregulated miRNA and downregulated mRNAs; simultaneously, there were 583 binding points between downregulated miRNA and upregulated mRNAs. These changed mRNA may potentially involve the following signaling pathways: Insulin secretion, pancreatic secretion, mammalian target of rapamycin signaling pathway, forkhead box O signaling pathway and phosphatidylinositol 3-kinase protein kinase B signaling. The fluctuating effects of miRNAs and matched mRNAs indicated that miRNAs may have wide cross-talks with mRNAs in pancreatic tissues of type 1 diabetic mice. The cross-talks may play important roles in contributing to impaired islet functions and the development of diabetes. However, further functional validation should be conducted in the future. PMID- 26137233 TI - Topical application of a cleanser containing extracts of Diospyros kaki folium, Polygonum cuspidatum and Castanea crenata var. dulcis reduces skin oil content and pore size in human skin. AB - The effects of skin pores on skin topographic features can be reduced by decreasing excessive production and accumulation of sebum and elimination of comedones. Therefore, a cosmetic cleanser that regulates sebum homeostasis is required. In the present study, the effects of a cosmetic cleanser that contained Diospyros kaki folium, Polygonum cuspidatum and Castanea crenata var. dulcis (DPC) was examined on the removal of sebum and on skin pore size. Healthy volunteers (n=23) aged 20-50 years were asked to apply the test materials to the face. Skin oil content, pore size, pore number and extracted sebum surface area were measured using various measurement methods. All the measurements were performed at pre- and post-application of the test materials. When the cosmetic cleanser containing DPC was applied to the skin, the oil content decreased by 77.3%, from 6.19 to 1.40. The number of skin pores decreased by 24.83%, from 125.39 to 94.23. Skin pore size decreased from 0.07 to 0.02 um3 (71.43% decrease). The amount of extracted sebum increased by 335% when the DPC cleanser was used. Compared to the control cleanser, skin oil content was significantly decreased when the cleanser that contained DPC was used. The cleanser containing DPC also decreased pore size and number. Finally, the DPC cleanser easily removed solidified sebum from the skin. PMID- 26137234 TI - Association of genetic variants of the alpha-kinase 1 gene with type 2 diabetes mellitus in a longitudinal population-based genetic epidemiological study. AB - Previously, our studies identified nine genes and the chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke or chronic kidney disease in individuals by genome-wide or candidate gene association studies. The present study examined the possible association of 13 polymorphisms at these 10 loci with the prevalence of type 2 diabetes mellitus (DM) in community-dwelling individuals. Study subjects comprised 6,027 individuals (797 subjects with type 2 DM and 5,230 controls) who were recruited to the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited for an annual health checkup and they were followed up each year (mean follow-up, 5 years). Longitudinal analysis with a generalized estimating equation and with adjustment for age, gender and body mass index (BMI) revealed that rs2116519 (C->T) of FAM78B (P=0.0188), as well as rs2074379 (G->A, P=0.0121) and rs2074388 (A->G, P=0.0053) of ALPK1 were significantly (P<0.05) associated with the prevalence of type 2 DM. Longitudinal analysis with a generalized linear mixed-effect model and with adjustment for age, gender and BMI among all the individuals revealed that rs2116519, rs2074379 and rs2074388 were significantly associated with fasting plasma glucose level (P=0.0352, 0.0017 and 0.0010, respectively) and to blood glycosylated hemoglobin (hemoglobin A1c) content (P=0.0065, 0.0090 and 0.0079, respectively). Similar analysis among individuals not taking antidiabetic medication revealed that rs2074379 and rs2074388 were associated with the fasting plasma glucose level (P=0.0073 and 0.0042, respectively) and blood hemoglobin A1c content (P=0.0142 and 0.0126, respectively), whereas rs2116519 was associated with blood hemoglobin A1c content only (P=0.0470). ALPK1 may thus be a susceptibility gene for type 2 DM. PMID- 26137235 TI - Effect of Brazilian green propolis in patients with type 2 diabetes: A double blind randomized placebo-controlled study. AB - Propolis contains a variety of chemical compounds, including polyphenols, flavonoids, phenolic aldehydes, amino acids and vitamins, and presents numerous biological and pharmacological properties. The aim of the present study was to evaluate the effect of propolis on blood examination data in patients with type 2 diabetes. In the double-blind, 8-week randomized controlled study, 80 patients with type 2 diabetes were enrolled. Patients were randomly assigned to receive Brazilian green propolis (226.8 mg/day for 8 weeks) (n=41) or the placebo (n=39). The primary endpoint was to detect changes in blood examination data associated with metabolic disorders in patients suffering from diabetes mellitus, including the homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and estimated glomerular filtration rate (eGFR) from baseline to the end of this study. The value of HOMA-IR was not significantly changed by the 8-week administration of propolis or placebo from the baseline data. Values of blood uric acid and eGFR in patients taking the placebo became worse at 8 weeks compared to the baseline, whereas this did not occur in patients consuming Brazilian green propolis. However, HOMA-IR was not improved by propolis intake. A randomized, controlled 8-week trial suggests that Brazilian green propolis (226.8 mg/day) prevents patients with type 2 diabetes from developing worse blood uric acid and eGFR. PMID- 26137236 TI - Inhibiting Rho kinase 2 reduces memory dysfunction in adult rats exposed to sevoflurane at postnatal days 7-9. AB - The aim of the present study was to investigate the roles of Rho protein A (RhoA) and Rho kinases 2 (ROCK2) in the memory dysfunction of adult rats exposed to sevoflurane at postnatal days 7-9 (P7-9). One-week-old Sprague-Dawley rats were divided into four groups known as C, S1, S3 and F. Rats in the S1 (2 h at P7) and S3 groups (2 h/day at P7-9) were exposed to sevoflurane. The rats in the F group were treated with the ROCK2 inhibitor and subsequent sevoflurane exposure (2 h/day at P7-9). The rats in the C group received no sevoflurane. The protein levels of RhoA, ROCK2 and cleaved caspase-3 (Cl-Csp3) in the adult hippocampus were assessed by western blot analysis. Learning and memory of rats at postnatal 45-50 days (P45-50) were detected by the Morris water maze (MWM) test. During the training of MWM, the latency and distance of rats in the S3 group were significantly longer than that of the C group (P<0.05, respectively). In the probe test, the percentages of time and distance in the target quadrant for the S3 group were evidently less than that of the C group (P<0.05). There was no significant difference in the behaviors between the C and S1 groups (P>0.05, respectively). Corresponding to the behavioral changes, the levels of RhoA, ROCK2 and Cl-Csp3 in the hippocampus of the S3 group significantly increased, compared to that of the C and S1 groups (P<0.05). Additionally, the ROCK2 inhibitor clearly decreased ROCK2 and Cl-Csp3 expression and shortened the latency during the training (P<0.05, P46-49 respectively) and probe test (P<0.05) in the F group, compared to that of the S3 group. Compared to the C group, the expression of RhoA, ROCK2 and Cl-Csp3 in the hippocampus of the S1 group had no significant difference (P>0.05). Multiple inhalation of sevoflurane can induce neurotoxicity and memory dysfunction. RhoA and ROCK2 played important roles in the impairment of learning and memory of adults rats exposed to sevoflurane at the postnatal early stage. PMID- 26137237 TI - Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats. AB - Approximately 42% of patients with sepsis undergo acute kidney injury (AKI), which evidently influences patient survival. However, effective therapy strategies are lacking, thus, the present study investigated the protective effects of dexmedetomidine (DEX), a highly selective alpha-2 adrenoceptor agonist, in rat sepsis models. Rat sepsis models were generated through lipopolysaccharide injection (LPS; 5 mg/kg) in the tail vein. Rats were pretreated with DEX (10 ug/kg) 10 min before LPS injection to observe its protective effects. Of note, a unique alpha-2-adrenergic receptor antagonist, yohimbine (YOH; 1 mg/kg, intraperitoneally), was also used to antagonize the protective effects of DEX 30 min before DEX exposure. Thirty-two male Sprague Dawley rats were randomly divided into the Sham, LPS, DEX + LPS and YOH + DEX + LPS groups (n=8/group). All the rats were sacrificed 4 h later to observe the pathological changes of renal tissue, including plasma creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1) and high mobility group protein 1 (HMGB-1) expression. Interleukin 6 (IL-6), IL-18 and tumor necrosis factor alpha (TNF-alpha) were all determined to examine the mechanisms of LPS induced AKI relative to inflammatory reaction. The results indicated that AKI induced by LPS was serious. Renal pathological injury, plasma Cr, BUN, IL-6, IL 18 and TNF-alpha were all evidently increased in varying degrees. KIM-1 and HMGB 1 expression was upregulated in the LPS group (P<0.05 vs. Sham group). However, when rats were pretreated with DEX, AKI induced by LPS was decreased significantly. Renal pathological injury, plasma Cr, BUN, IL-6, IL-18, TNF-alpha, and KIM-1 and HMGB-1 expression were all reduced (P<0.05 vs. LPS group). In addition, exposure of the alpha-2-adrenergic receptor antagonist, YOH, eliminated this reduction. In conclusion, DEX protected against sepsis-induced AKI through depressing the inflammatory reaction, mechanisms of which may be associated with alpha-2 receptors inhibition. PMID- 26137238 TI - mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia. AB - BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance. PMID- 26137239 TI - Isolation and genetic characterization of enterovirus in patients with febrile rash illness. AB - Measles and rubella virus are usually considered as the causative agents in patients with febrile rash illness (FRI). However, investigators have identified that enteroviruses are also associated with FRI, and the present study was undertaken to investigate this association. In the study, 20 throat swab samples were collected from patients suffering from rash and fever between April and July in 2013. The 20 samples tested negative for measles virus, but all were positive when reverse transcription-polymerase chain reaction was performed using enterovirus universal primers. Specifically, five tested positive for Coxsackie B3 virus (CVB3). The titers of the five CVB3 isolates were 106.5, 106.4, 107.5, 106.5 and 106.5 tissue culture infectious dose50/100 ul respectively. The partial VP1 sequences of the five CVB3 isolates were identical to each other and were closely associated with the CVB3/MKP and CVB3/Macocy strains, which are known to induce myocarditis and neonatal diseases of the central nervous system. In conclusion, CVB3 may cause symptoms of fever and rash and should be differentiated from measles, rubella and other infectious pathogens. The five CVB3 isolates described in the study were genetically similar to each other and to other local CVB3 strains. The results provide further data on the viral pathogen spectrum associated with FRI. PMID- 26137240 TI - Blood gas analysis of the coronary sinus in patients with heart failure. AB - The difference in cardiac oxygen consumption between individuals with normal cardiac function and those with heart failure (HF), and the association between cardiac oxygen consumption and cardiac ejection fraction (EF) are poorly understood. By establishing a control group composed of individuals with normal cardiac function, the present study aimed to determine the difference in cardiac oxygen consumption between individuals with normal and abnormal cardiac function, as well as the association between cardiac oxygen consumption and cardiac EF. A total of 34 patients with normal cardiac function were enrolled in the control group and 44 patients with HF were enrolled in the experimental group. Blood samples from the aortic root, femoral vein and coronary sinus (CS) were collected from each patient. All the blood samples were subjected to blood gas analysis. The partial pressure of oxygen and oxygen saturation obtained from the peripheral vein and CS of patients with HF were lower than those in patients with normal cardiac function. In each patient with HF, the association between cardiac oxygen consumption and cardiac EF was analyzed using multi-linear correlation and regression analyses. Cardiac oxygen consumption negatively correlated with cardiac EF (R=-0.336, P=0.026). Furthermore, linear regression analysis suggested that cardiac EF had a significant effect on cardiac oxygen consumption (y = 82.906-0.483*, P=0.026). In conclusion, myocardial oxygen consumption is greater in individuals with HF compared to those with normal cardiac function. The cardiac EF affects myocardial oxygen consumption in patients with HF. PMID- 26137241 TI - Measurement of hair iron concentration as a marker of body iron content. AB - The aim of the present study was to define the possible association between blood parameters and hair iron concentration in patient groups showing a difference in body iron content. The study population comprised subjects with iron deficiency anaemia and transfusion-related anaemia with different body iron contents and a healthy control group. All the cases included in the study were examined with respect to hair iron concentration, serum iron, total iron-binding capacity (TIBC), transferrin saturation and erythrocyte markers in the total blood count with ferritin values. Differences in hair iron concentration were evaluated between the groups. Correlation analysis was applied to define the association between the laboratory values used as markers of body iron content and hair iron concentration. A statistically significant difference was determined in hair iron 56Fe and 57Fe concentrations between the group with transfusion-related anaemia, the iron deficiency anaemia group and the healthy control group (P<0.001). In addition, a positive correlation was determined between hair iron 56Fe and 57Fe concentrations and serum iron, ferritin level, transferrin saturation, mean erythrocyte volume and mean erythrocyte haemoglobin values and a negative correlation with TIBC. In conclusion, the results of the present study showed a statistically significant difference in the hair iron concentrations of the patient groups with different body iron content and these values were correlated to the laboratory markers of body iron content. PMID- 26137242 TI - The association between mean platelet volume and chronic atrial fibrillation and the presence of thrombotic events. AB - Mean platelet volume (MPV), a marker of platelet activation, is a surrogate marker of platelet function and a potential mediator of the association between inflammation and thrombosis. The present retrospective study sought to investigate the association between MPV and the presence of thrombotic events (TEs) in patients with chronic atrial fibrillation (AF). A total of 114 consecutive patients with chronic AF were enrolled from a Chinese hospital. Individuals were divided into three groups: The AF+TE group (n=57, 33.1%), which comprised patients in AF with concomitant TEs; the AF group (n=57, 33.1%), which comprised patients in AF with no identifiable TEs, as confirmed by brain computed tomography, transesophageal echocardiography, or a combination of the two; and a control group (n=58, 33.7%), which consisted of patients who were in sinus rhythm. MPV, high-sensitivity C-reactive protein (hsCRP), D-dimer and the left atrial diameter (LAD) were analyzed in the 172 participants. The MPV level of patients in the AF+TE group was significantly higher than that of patients in the AF and control groups (P<0.05). In the correlation analysis, MPV levels were found to be positively correlated with LAD, D-dimer concentrations and hsCRP levels in patients with AF (r=0.960, P<0.05; r=0.896, P<0.05; and r=0.924, P<0.01, respectively). In the receiver operating characteristic curve analysis, the value for MPV levels required to detect TEs with a sensitivity of 77.5% and specificity of 78% was 10.5 femtoliter (fl). A high MPV level (>10.5 fl) was significantly associated with the occurrence of TEs (odds ratio, 3:1; 95% confidence interval, 1.6-5.1; P=0.000). The results of the present study suggest that an additional biomarker, MPV, has a predictive value for the presence of TEs in patients with AF. MPV may be a potential mediator between inflammation and thrombosis. PMID- 26137243 TI - Matrix metalloproteinase-1 expression in breast cancer and cancer-adjacent tissues by immunohistochemical staining. AB - Although matrix metalloproteinase-1 (MMP-1) has been considered a factor of crucial importance for breast cancer cells invasion and metastasis, the expression of MMP-1 in different breast cancer and cancer-adjacent tissues have not been fully examined. In the present study, immunohistochemical staining was used to detect the MMP-1 expression in non-specific invasive ductal carcinoma of the breast, cancer-adjacent normal breast tissue, lymph node metastatic non specific invasive ductal carcinoma of the breast and normal lymph node tissue. The results showed that MMP-1 expression is different in the above tissues. MMP-1 had a positive expression in normal lymph node tissue and lymph node metastatic non-specific invasive ductal carcinoma. The MMP-1 negative expression rate was only 6.1% in non-specific invasive ductal carcinoma of the breast and 2.9% in cancer-adjacent normal breast tissue respectively. MMP-1 expression is higher in non-specific invasive ductal carcinoma and lymph node metastatic non-specific invasive ductal carcinoma compared to cancer-adjacent normal breast tissue and normal lymph node tissue. In conclusion, higher expression of MMP-1 in breast cancer may play a crucial role in promoting breast cancer metastasis. PMID- 26137244 TI - Expression of the genes encoding kinin receptors are increased in human carotid atherosclerotic plaques. AB - There is increasing evidence showing that inflammation occurs in atherosclerosis and contributes to the formation of atherosclerotic plaques. As important inflammatory peptides, kinins are increased in inflammation, eliciting vasodilation, increasing vascular permeability and recruiting inflammatory cells to the injury sites by activating specific receptors, B1 and B2. The two receptors have been reported to increase in inflammation, but their expressions remain to be defined in human carotid atherosclerotic plaques (CAP). In order to assess the gene expression of kinin receptors in human CAP, 47 CAP specimens were collected from patients undergoing endarterectomy and classified into stable and unstable plaque groups, respectively, with 10 mesenteric arteries used as controls. Total mRNA of B1R and B2R was extracted from CAPs and their levels were determined using reverse transcription-polymerase chain reaction. The expression of B1R and B2R mRNA was significantly upregulated in human CAPs compared to the control arteries. In the unstable plaques, the ratios of B1R to the beta-actin mRNA level were significantly increased relative to the stable plaques. However, no notable differences were observed in the ratios of B2R to beta-actin in mRNA expression between the stable and unstable plaques. The present study suggests that kinin-mediated inflammation involves the formation of atherosclerotic plaque and B1R plays an important role in plaque instability, indicating that kinin receptors can be used as potential targets for future therapeutic interventions. PMID- 26137245 TI - Effects of Feijining Decoction on vascular endothelial growth factor protein expression and changes of T cell subsets in Lewis lung carcinoma-bearing mice. AB - Angiogenesis is crucial for cancer growth and metastasis. T cells are also key members of the adaptive immunity against tumorigenesis. The aim of the present study was to observe the effects of Feijining Decoction (FJND) on vascular endothelial growth factor (VEGF) protein expression and T cell subsets [cluster of differentiation 4+(CD4+) and CD8+ T lymphocyte] in Lewis lung carcinoma (LLC) bearing mice. C57BL/6J mice were subcutaneously implanted with LLC cells. Forty carcinoma-bearing mice were randomly assigned to four groups (10 animals/group). The control group (CG) were the untreated group, the cisplatinum (DDP) group (DG) mice were treated with DDP, the FJND group (FG) were treated with FJND and the FJND + DDP group (FDG) were treated with FJND and DDP. Western blot and flow cytometry were used to evaluate the VEGF protein expression of tumor tissue and T cell subsets of the spleen. Spontaneous activity in 5 min was observed by the photoelectric counting method. DDP + FJND (FDG group) markedly inhibited tumor growth compared to the DG mice. The protein expression of VEGF was significantly downregulated in the carcinoma of FG mice compared to CG mice. VEGF protein expression was significantly reduced in FDG compared to DG mice. In the FG mice, the splenic CD4+ and CD4+/CD8+ cells were significantly increased compared to the CG mice, and the splenic CD4+ cells in the FDG mice were significantly increased compared to the DG group. In conclusion, FJND can inhibit tumor growth by downregulating VEGF protein expression and improving the immune function. PMID- 26137246 TI - Volatile anesthetic sevoflurane ameliorates endotoxin-induced acute lung injury via microRNA modulation in rats. AB - Volatile anesthetics have a lung protective effect in acute lung injury (ALI). Our previous study showed sevoflurane affects the expression of microRNA (miRNA) that control various physiological systems by regulating messenger RNA (mRNA) expression. However, the association between the anti-inflammatory effect of sevoflurane and miRNAs modulation remains unknown. The aim of the present study was to investigate the effect of sevoflurane and the expression of miRNAs in an endotoxin-induced ALI model in rats. Wistar rats were randomly assigned to three groups [lipopolysaccharide (LPS), LPS-sevoflurane and control; n=8/group]. All the rats were mechanically ventilated and intravenously-administered LPS (saline as control). Two hours post-injury, general anaesthesia was performed for 4 h with 2% sevoflurane (LPS-sevoflurane). The LPS and the control groups did not receive anaesthesia. The severity of ALI was evaluated by partial pressure of oxygen/fraction of inspired oxygen and the mRNA expression of inflammatory cytokine. The miRNA expression in lung tissue was analyzed by a reverse transcription-quantitative polymerase chain reaction. LPS caused ALI, evidenced by the impairment of pulmonary function and increased mRNA levels of tumor necrosis factor-alpha, interleukin-6 and nuclear factor-kappaB. Sevoflurane improved pulmonary function and inhibited the increased mRNAs. Of the 219 miRNAs detected, 15 and nine miRNAs were significantly changed in the LPS and LPS sevoflurane group, respectively. In the LPS-sevoflurane group, the expression of several miRNAs that regulate inflammation was significantly changed compared to the LPS group. In conclusion, the present data showed that sevoflurane influences the expression of the miRNAs that regulate inflammation. This result suggests that the changes in miRNA expression are involved in the lung protective mechanisms of volatile anesthetics. PMID- 26137247 TI - Association of genetic variants with coronary artery disease and ischemic stroke in a longitudinal population-based genetic epidemiological study. AB - Our previous studies identified nine genes and chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke or chronic kidney disease by genome-wide or candidate gene association studies. As coronary artery disease (CAD) and ischemic stroke may share genetic architecture, certain genetic variants may confer susceptibility to the two diseases. The present study examined the association of 13 polymorphisms at these 10 loci with the prevalence of CAD or ischemic stroke in community-dwelling individuals, with the aim of identifying genetic variants that confer susceptibility to the two conditions. Study subjects (170 with CAD, 117 with ischemic stroke and 5,718 controls) were recruited to the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited for an annual health checkup and they were followed up each year (mean follow-up period, 5 years). Longitudinal analysis with a generalized estimating equation, and with adjustment for age, gender, body mass index, smoking status, the prevalence of hypertension, diabetes mellitus and dyslipidemia and the serum concentration of creatinine, revealed that rs2074380 (G->A) and rs2074381 (A->G) of the alpha-kinase 1 (ALPK1) gene and rs8089 (T->G) of the thrombospondin 2 (THBS2) gene were significantly (P<2*10-16) associated with the prevalence of CAD, with the AA genotype of rs2074380 and GG genotypes of rs2074381 and rs8089 being protective against this condition. Similar analysis revealed that rs9846911 (A->G) at chromosome 3q28, rs2074381 of ALPK1, rs8089 of THBS2 and rs6046 (G->A) of the coagulation factor VII gene were significantly (P<2*10-16) associated with the prevalence of ischemic stroke, with the GG genotypes of rs9846911, rs2074381 and rs8089 and the AA genotype of rs6046 being protective against this condition. ALPK1 and THBS2 may thus be susceptibility loci for CAD and ischemic stroke. PMID- 26137248 TI - Expression of various protection of telomeres 1 variants is associated with telomere length and radiosensitivity in colon and gastric adenocarcinoma cells in vitro. AB - Protection of telomeres 1 (POT1) is a telomere-binding protein, which binds to the single-stranded DNA extensions of telomeres and regulates telomere length. Different POT1 mRNA variants were examined and compared with telomere length and radiosensitivity in colon and gastric adenocarcinoma cells. POT1 production and telomere lengths were assessed using 10 human cancer cell lines by quantitative polymerase chain reaction (qPCR). POT1 mRNA levels, which were relatively stable, were significantly correlated with telomere length in gastric cancer cells and colon cancer cells, except for HT29 (P<0.01). POT1 v5 indexes were closely associated with radiosensitivity in colon cancer cells and gastric cancer cells (P<0.05). In conclusion, POT1 may be a good marker for the examination of cell specific telomere length and radiosensitivity. PMID- 26137249 TI - Effect of acute heat stress on adrenocorticotropic hormone, cortisol, interleukin 2, interleukin-12 and apoptosis gene expression in rats. AB - The aim of the present study was to investigate the effect of acute heat stress on the neuroendocrine and immunological function in rats. Male Sprague-Dawley rats were randomly divided into two groups and respectively exposed to heat (32 degrees C) or to room temperature (24 degrees C). After 7 days of heat exposure, the heat-stress rat model was established. The organ coefficients of the pituitary and adrenal glands were determined. The body temperature was measured by telemetry. The average contents of adrenocorticotropic hormone (ACTH), cortisol (Cor), interleukin-2 (IL-2) and IL-12 in serum were detected. The expression of apoptotic genes in the spleen was measured. The results showed that acute heat stress did not evidently affect the body temperature and body weight (P>0.05), but the exposure increased the organ coefficients of the pituitary and adrenal glands (P<0.05). Heat exposure significantly elevated the level of ACTH, Cor, IL-2 and IL-12 (P<0.05). The expression of caspase-3 and Bax were not changed significantly (P>0.05), while Bcl2 was reduced (P<0.05). PMID- 26137250 TI - Ophiopogon japonicus strains from different cultivation regions exhibit markedly different properties on cytotoxicity, pregnane X receptor activation and cytochrome P450 3A4 induction. AB - Maidong, known as Ophiopogon japonicus, is one of the two basic ingredients of Shenmai injection, which is a widely used herbal preparation in traditional Chinese medicine (TCM) for the treatment of atherosclerotic coronary heart disease and viral myocarditis. Previously, the ethanol extract of Maidong activated the pregnane X receptor (PXR) signaling pathway and induced the cytochrome P450 3A4 (CYP3A4) reporter gene and raised the concern of herb-drug interactions (HDIs) when Maidong was used in combination with prescribed drugs metabolized by CYP3A4. Therefore, the present study further investigated and compared the differences of the ethanol and aqueous extracts (ee- and ae-, respectively) of two Maidong strains, known as Zhe Maidong (ZM) and Chuan Maidong (CM). Cytotoxicity, PXR activation and CYP3A4 induction by the 3-(4,5) dimethylthiahiazo-(-z-y1)-3,5-diphenytetrazoliumromide assay, reporter gene assay and reverse transcription-quantitative polymerase chain reaction analysis were examined. The observations showed that ee-ZM demonstrated a significantly higher cytotoxicity, a relatively weaker PXR activation capability and a markedly stronger CYP3A4-inducing capacity than ee-CM. Compared to ae-CM, ae-ZM exhibited only a slight or no difference on cytotoxicity and CYP3A4 induction, while a significant lower level of PXR activation was apparent. Collectively, Maidong from different producing areas possess different properties upon cytotoxicity and the drug-metabolizing enzyme inducing effect, and attention should be paid to the selection of Maidong strains from different planting regions into TCM preparations for reducing potential adverse reactions and HDIs. PMID- 26137251 TI - CKS2 in human cancers: Clinical roles and current perspectives (Review). AB - Cyclin-dependent kinase subunit 2 (CKS2) is indicated in the processes of cell cycle and cell proliferation. Through these processes, CKS2 is identified as a cancer gene, but its role has not been well reviewed. The aim of the present study was to summarize the clinicopathological significance and the molecular mechanisms of CKS2 in human cancers. Its expression was upregulated in the majority of the types of cancer studied. CKS2 was shown to have a function in cancers of the digestive tract, genital tract, thyroid, nerve and certain other types of cancer. CKS2 can promote progression of certain cancers via positive control of proliferation, invasion and migration. Downregulation of CKS2 induces cancer cell apoptosis. CKS2 can change a multitude of cellular mechanisms in cancer pathogenesis by regulating the gene translation of numerous validated targets, such as p53, CDK1, cyclin A, cyclin B1, caspase-3 and Bax. In addition, the molecular mechanism that causes aberrant expression of CKS2 was epigenetic modification of miR-26a and the Y-box-binding protein 1 (YB-1) gene. In conclusion, CKS2 is commonly elevated in cancer, most likely due to its ability to promote cancer cell growth, invasion and migration through regulating certain significant genes. Understanding the mechanisms by which CKS2 is involved with cancer pathogenesis will be useful in the development of tumor therapy for patients with cancer. PMID- 26137252 TI - Expression of insulin-like growth factor I receptor as a biomarker for predicting prognosis in biliary tract cancer patients. AB - Carcinomas of the gallbladder (GBCa) and bile ducts are aggressive tumors with poor survival and it is, therefore, essential to elucidate the molecular mechanisms of the various signaling pathways in order to develop effective therapies. In this study, tumor specimens from 40 GBCa patients, 12 extrahepatic bile duct carcinoma patients and 26 intrahepatic bile duct carcinoma patients from the USA and Japan were investigated for insulin-like growth factor I receptor (IGF-IR), mammalian target of rapamycin (mTOR) and rapidly accelerated fibrosarcoma-1 (Raf-1) expression by immunohistochemistry; in addition, the correlations with histological type, pathological stage and patient outcome were analyzed. Positive expression of IGF-IR, mTOR and Raf-1 were identified in 68, 73 and 85% of the specimens, respectively. There was no association with histological type and pathological stage, although the positive expression rate of Raf-1 was higher in advanced-stage GBCa. Moreover, patients with positive expression of IGF-IR exhibited significantly reduced survival compared to those with negative IGF-IR expression. In conclusion, IGF-IR, mTOR and Raf-1 were highly expressed in biliary tract cancer and targeted therapy against IGF-IR may be an effective strategy. Among these molecules, IGF-IR expression was found to be a useful biomarker for identifying patients who may benefit from additional treatment. PMID- 26137253 TI - Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-beta in patients with advanced gastric cancer: A randomized clinical trial. AB - Systemic abrogation of TGF-beta signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide-Kureha (PSK) into tumor-bearing mice also showed tumor regression with reduced TGF-beta. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF-beta. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF-beta was measured pre- and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF-beta ranged from 1.85-43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly-differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF-beta (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF-beta remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF-beta between groups A and B (P=0.019). PSK reduced the plasma TGF-beta in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF-beta by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC. PMID- 26137254 TI - Extracranial metastasis of gliobastoma: Three illustrative cases and current review of the molecular pathology and management strategies. AB - Glioblastoma (GBM) is the most common and the most malignant primary brain tumor in adults, accounting for ~12-15% of all intracranial neoplasms. Despite advances in surgical, medical and radiation therapies, the mortality of GBM remains high, with a median survival ranging between 40 and 70 weeks. Similar to other primary brain tumors, the extracranial metastasis of GBM is extremely rare, occurring in <2% of patients. To demonstrate the clinical characteristics of this rare tumor, we herein present three cases of extracranial GBM metastasis: One to the lungs, which represents the longest reported survival of lung metastases from GBM to date; the second to the soft tissue of the posterior neck; and the third to the lumbar intradural space. Unlike tumors elsewhere, there are unique barriers in the brain that prevent the hematogenous and lymphatic spread of intracranial tumors, such as the dura mater and the thickened basement membrane of the blood vessels. In addition, central nervous system tumor cells lack extracellular matrix proteins required to invade surrounding connective tissue, a prerequisite for tumor dissemination. In this study, we aimed to investigate the different possible mechanisms underlying the extracranial metastasis of GBM and determine the biomolecular and genetic characteristics differentiating GBMs that metastasize from those that do not. We also reviewed the role of systemic chemotherapy and bevacizumab in the treatment of disseminated GBMs. Early identification and differentiation of these tumors may enable patients to benefit from surgical resection, radiation and combination chemotherapy prior to developing other comorbidities from metastatic disease, which may translate into prolonged survival with an acceptable quality of life. PMID- 26137255 TI - miR-615-3p expression level in bone marrow is associated with tumor recurrence in hepatocellular carcinoma. AB - The significance of disseminated tumor cells (DTCs) in bone marrow (BM) on tumor recurrence has not been investigated in patients with hepatocellular carcinoma (HCC). The aim of te present study was to clarify the molecular characteristics of DTCs that affect postoperative recurrence based on microRNA (miRNA) expression profiles in clinical HCC patients undergoing curative resection. DTCs were prospectively collected from the BM of preoperative HCC patients using immunomagnetic beads and subjected to miRNA microarray analysis. Microarray analysis of nine HCC patients (n=5 patients with postoperative HCC recurrence, n=4 patients without HCC recurrence) demonstrated that miR-615-3p is significantly upregulated in the DTCs of patients with recurrence compared to the DTCs from patients without recurrence. In vitro experiments demonstrated that the miR-615-3p expression level is significantly correlated with malignant characteristics in HCC cells. These data suggest that miR-615-3p in DTCs may play an important role in postoperative HCC recurrence, which suggests that miR-615-3p is a potential target molecule for regulating postoperative HCC recurrence. PMID- 26137256 TI - Postoperative infection and survival in osteosarcoma patients: Reconsideration of immunotherapy for osteosarcoma. AB - There is controversy regarding the impact of infection on long-term prognosis in osteosarcoma patients. Clinical trials and experiments relating to this field could bring reconsideration of immunotherapy for osteosarcoma. The clinical records were reviewed of 125 osteosarcoma patients with a mean follow-up of 5.1+/ 3.9 years (range, 0.5-19.8 years), and a review of the literature was also carried out. Chronic localized infections (but not systemic infection) were determined in 6 patients (4.8%). Similar chemotherapeutic regimens (P=1.00) and histological reactions (P=0.65) were observed in patients with or without infection. Tumor location of proximal tibia (P=0.04) was more common in infected patients. More amputations (P<0.001) were necessitated in infected patients due to uncontrolled infection. The 5-year overall survival rate and event-free survival rate in infected patients were 100%, which were significantly higher than that of the non-infected patients, of whom the rates were 54 and 43% respectively (log-rank test: total survival, P=0.01; tumor-free survival, P=0.01). Distant metastasis was an independent risk factor for survival determined by Cox regression analysis (P<0.001, 95 confidence interval, 1.59 3.98). These findings suggested infection was likely to have positive effects on survival in osteosarcoma patients, however, underlying mechanisms remain to be elucidated. Reconsideration of the association of infection and survival in osteosarcoma patients will help to explore novel therapeutic routes and targets in these patients. PMID- 26137257 TI - Clinical multifactorial analysis of early postoperative seizures in elderly patients following meningioma resection. AB - The aim of the present study was to identify the major factors correlated with early postoperative seizures in elderly patients who had undergone a meningioma resection, and subsequently, to develop a logistic regression equation for assessing the seizures risk. Fourteen factors possibly correlated with early postoperative seizures in a cohort of 209 elderly patients who had undergone meningioma resection, as analyzed by multifactorial stepwise logistic regression. Phenobarbital sodium (0.1 g, intramuscularly) was administered to all 209 patients 30 min prior to undergoing surgery. All the patients had no previous history of seizures. The correlation of the 14 clinical factors (gender, tumor site, dyskinesia, peritumoral brain edema (PTBE), tumor diameter, pre- and postoperative prophylaxes, surgery time, tumor adhesion, circumscription, blood supply, intraoperative transfusion, original site of the tumor and dysphasia) was assessed in association with the risk for post-operative seizures. Tumor diameter, postoperative prophylactic antiepileptic drug (PPAD) administration, PTBE and tumor site were entered as risk factors into a mathematical regression model. The odds ratio (OR) of the tumor diameter was >1, and PPAD administration showed an OR >1, relative to a non-prophylactic group. A logistic regression equation was obtained and the sensitivity, specificity and misdiagnosis rates were 91.4, 74.3 and 25.7%, respectively. Tumor diameter, PPAD administration, PTBE and tumor site were closely correlated with early postoperative seizures; PTBE and PPAD administration were risk and protective factors, respectively. PMID- 26137258 TI - MYC is expressed in the stromal and epithelial cells of primary breast carcinoma and paired nodal metastases. AB - The MYC oncogene is directly involved in the proliferation, metabolism, progression and distant metastasis of breast cancer. Since metastatic spread to the lymph nodes is often the first indication of propensity for metastatic dissemination, the MYC status in nodal disease may represent a decision-making variable. However, the analysis of MYC expression in stromal cells, namely cancer associated fibroblasts (CAFs), which are known to play a critical role in cancer progression, remains poorly reported. The aim of this study was to determine the expression of MYC and other markers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), p53, Ki67, epidermal growth factor receptor (EGFR), phosphorylated AKT (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) by immunohistochemistry in representative samples from 80 patients with ductal infiltrative breast cancer and 43 paired compromised axillary lymph nodes allocated in tissue microarrays (TMAs). The epithelial and stromal components of primary tumors and respective lymph node metastases were separately analyzed. MYC expression (cytoplasmic and nuclear) was a frequent event in the epithelial and stromal components of the primary tumors. The epithelial cells in the nodal metastases exhibited a trend for decreased MYC expression compared to that in the primary tumors (P=0.08) but retained the original status of the primary tumors for all other markers. The stromal cells were uniformly negative for ER, PR, HER2, p53, Ki67 and EGFR. Comparison of the stromas of primary tumors and respective lymph node metastases revealed a reduced frequency of nuclear MYC in 15% of the cases (P=0.003), whereas p-mTOR followed a similar trend (P=0.09). Analyses of the possible correlations among markers revealed that epithelial nuclear MYC was associated with p53 (P=0.048). This is an original study demonstrating a significant proportion of MYC expression (nuclear or cytoplasmic), as well p-mTOR and p-AKT expression, in the epithelial and stromal components of either the primary tumor or the nodal metastases. CAFs expressing MYC may establish an angiogenic microenvironment supporting cancer survival and facilitating colonization at the nodal metastatic site. PMID- 26137259 TI - Enhanced central memory cluster of differentiation 8+ and tumor antigen-specific T cells in prostate cancer patients receiving repeated in situ adenovirus mediated suicide gene therapy. AB - The high relapse rate of prostate cancer following radical prostatectomy is clinically problematic, and various neoadjuvant therapies aimed at reducing the rate have been examined. A previous study has shown that immune responses are increased in patients treated by adenoviral vector-mediated herpes simplex virus thymidine kinase (HSV-tk) gene delivery followed by ganciclovir (GCV) injection. However, details of the immune responses following this form of gene therapy remain unclear. Five patients who agreed to participate in the present phase I/II trial were repeatedly administered GCV intravenously for 2 weeks following intraprostatic injection of HSV-tk. Peripheral blood samples were periodically collected following the treatments, and lymphocyte subsets were analyzed by flow cytometry. Intracellular interferon (IFN)-gamma produced by T cells was further measured in response to prostatic acid phosphatase and NY-ESO-1 overlapping peptides. Central memory (CM) cluster of differentiation 8+ (CD8+) T cells were found to increase markedly during the second round of treatment. In three patients, tumor antigen-specific T cells were clearly increased following HSV-tk + GCV treatment. An increase in prostate cancer antigen-specific T cells and CM CD8+ T cells may contribute to a reduction of relapse rates in prostate cancer patients receiving this form of gene therapy, which shows promise in a neoadjuvant setting. PMID- 26137260 TI - Significant cytostatic effect of everolimus on a gefitinib-resistant anaplastic thyroid cancer cell line harboring PI3KCA gene mutation. AB - We previously demonstrated the efficacy of gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), on an anaplastic thyroid cancer (ATC) cell line. We also observed that gefitinib was not effective in regulating cell growth in a different ATC cell line that exhibited an altered EGFR-initiated signal transduction pathway. In the present study, we attempted to regulate the downstream effector of EGFR-Akt-mammalian target of rapamycin (mTOR) pathway by an mTOR inhibitor, everolimus. A total of 8 ATC cell lines were employed, 7 of which were established in our institute. OCUT-2 was known to carry a mutation in the phosphoinositide-3-kinase, catalytic, alpha polypeptide gene (PI3KCA) and to be gefitinib-resistant, whereas ACT-1 exhibited a remarkable growth arrest by gefitinib. All the cell lines were tested for the cytotoxic effect of everolimus. The mechanisms of cellular toxicity were investigated by EGFR stimulation, cell cycle and concurrent exposure to paclitaxel. In OCUT-2, but not in any of the other cell lines, everolimus achieved a significant growth inhibition (inhibition of 30 and 50% was achieved by concentrations of 0.8 and 5 nM, respectively). The growth in OCUT-2 was inhibited by everolimus, even with concordant EGFR stimulation. This effect was demonstrated by a G2M cell cycle arrest. An additive effect of everolimus onto the cytotoxic effect of paclitaxel was demonstrated at a dose of 1-2 nM. A significant growth inhibitory effect of everolimus on the gefitinib-resistant ATC cell line was demonstrated, suggesting a possible correlation between the efficacy of everolimus and PI3KCA gene mutation and the significance of molecular-targeted therapy in the management of ATC. PMID- 26137261 TI - Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest. AB - In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S 1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer. PMID- 26137263 TI - Complications in advanced or recurrent gastric cancer patients with peritoneal metastasis during and after palliative systemic chemotherapy. AB - Peritoneal metastasis (PM) in gastric cancer (GC) is often the cause of several complications, including ascites and bowel obstruction. The prognosis of patients with extensive PM is poor. There are only limited data available on clinical characteristics regarding the period between the initiation of chemotherapy until the death of the patient. We conducted a retrospective study to determine the frequency of major events during and after palliative chemotherapy in advanced GC patients with PM. The records of patients who received first-line palliative chemotherapy at the Tochigi Cancer Center for locally advanced or metastatic disease were reviewed. The extracted information included treatments received and emerging complications. Overall survival was compared between patients with and those without PM. A total of 97 patients were reviewed and the prevalence of complications with or without concurrent PM were as follows: bowel obstruction: PM, 37% (16/43) and non-PM, 20% (11/54) (P=0.0664); ascites: PM, 49% (21/43) and non-PM, 7% (4/54) (P<0.0001). The clinical characteristics of patients with PM from GC are unique. Therefore, it is crucial to consider PM as a predictive sign and an important factor when making clinical decisions and developing treatment strategies. PMID- 26137262 TI - Comparison of hand-assisted laparoscopic surgery and conventional laparotomy for rectal cancer: Interim results from a single center. AB - Minimally invasive laparoscopic surgery has become widespread and the indications for such surgery have recently been extended to various conditions, including rectal cancer. The objective of this study was to compare the clinical outcome of hand-assisted laparoscopic surgery (HALS) and conventional laparotomy (CL) in patients with rectal cancer. Patients who underwent radical resection of stage I III primary rectal cancer (n=111) were classified into those receiving HALS (n=57) and those receiving CL (n=54); the two groups were matched for stage and postoperative treatment. The 3-year relapse-free survival (3Y-RFS) and 3-year overall survival (3Y-OS) were calculated and compared between the two groups. Intraoperative blood loss, operating time, postoperative hospital stay and complications were also compared between the two groups. There were no significant differenceS in 3Y-RFS or 3Y-OS between the HALS and CL groups for patients with all-stage (I, II and III) rectal cancer. The mean (median) intraoperative blood loss was 344.0 (247.0) ML in the HALS group vs. 807.5 (555.5) ML in the CL group (P<0.001). The mean (median) postoperative hospital stay was 19.8 (17) and 25.5 (18.3) days, respectively (P=0.039). There were no significant differences in the operating time or the incidence of complications between the two groups. Based on these results, HALS was found to be comparable to CL regarding survival, while achieving less blood loss and a superior cosmetic outcome. However, longer follow-up is required to confirm these findings. PMID- 26137264 TI - Nedaplatin- versus cisplatin-based chemotherapy in the survival time of patients with non-small cell lung cancer. AB - Nedaplatin (NDP) has been extensively used to treat patients with non-small cell lung cancer (NSCLC) in the last decade. The present study compared the survival benefits of NDP and cisplatin (DDP) in the treatment of NSCLC. Patients (n=392) with NSCLC were treated with at least two cycles of platinum-based chemotherapy. Among these patients, 202 received DDP-based chemotherapy, and 190 received NDP based chemotherapy. The overall survival time of the two groups and the toxicity of drugs were analyzed. The results showed that only the chemotherapy cycle duration was found to be statistically different between DDP and NDP groups in all the characteristics. The mean chemotherapy duration was 3.3 cycles in the DDP group, and 4.1 cycles in the NDP group (chi2=20.206, P<0.001). Additionally, the chemotherapy cycle number was also an independent predictive factor for the overall survival time in the multivariate analysis (HR=0.539, P<0.001). The median survival time (MST) was 15 months in the DDP group, and 20 months in the NDP group (chi2=5.189, P=0.023). The 1-, 2- and 3-year overall survival rates were 62.4, 25.7 and 15.8%, and 78.9, 38.9, and 16.8% in the DPP and NDP groups, respectively. The incidence of grade 3-4 nausea/vomiting, anorexia and weight loss was higher in the DDP compared to the NDP group (36.1 vs. 8.4%, 17.3 vs. 5.8%, and 9.9 vs. 1%, respectively). In conclusion, NDP-based chemotherapy had a survival benefit compared to DDP-based chemotherapy for NSCLC patients, due to the lower toxicity of NDP, which renders this drug more tolerable, thus allowing patients to undergo more cycles of chemotherapy. PMID- 26137265 TI - Postoperative brachytherapy and electron beam irradiation for keloids: A single institution retrospective analysis. AB - The aim of the present study was to perform a retrospective analysis of the control rate and toxicity of postoperative brachytherapy and electron beam irradiation for keloids. A retrospective review was performed of 116 keloid patients who underwent postoperative brachytherapy and electron beam irradiation between January 1, 2002 and June 30, 2012. Several different radiotherapy techniques and fractionation schedules were performed in the analysis, including high-dose rate (HDR) irradiation with 192Ir at 8 Gy/1 fraction (F)+9 Gy/3F or 20 Gy/4F; HDR brachytherapy with 60Co at 20 Gy/4F or 18 Gy/6F; or external beam electron therapy at 26 Gy/13F or 30 Gy/15F. The endpoints of the study were analysis of the control rate and toxicity. The median observation period was 46.5 months (range, 10.0-120.0 months) for all patients. In total, 18 of the 116 patients relapsed, and 16.7 months (range, 10.0-30.0 months) was the median time to recurrence for these patients. The control rates for the patients who received hypofractionation (>2 Gy per fraction) and conventional fraction (2 Gy per fraction) were 88.5 and 76.3%, respectively (P=0.043). The control rates for the patients whose calculated biological effective doses (BED) were >30 Gy and <30 Gy were 89.7 and 79.3%, respectively (P=0.104). There were no grade 2 or higher adverse effects based on the Common Terminology Criteria for Adverse Events v3.0 in the late phase. No evidence was identified for a link between radiotherapy and the subsequent occurrence of cancer. The results of the present study indicate that hypofractionated radiotherapy played an important role as an adjuvant therapy following surgical excision of keloids. A BED of >30 Gy appears to be sufficient. No definitive evidence was found for an association between radiotherapy and the occurrence of cancer during the follow-up, however, more cases and longer follow-up periods are required. PMID- 26137266 TI - Oxaliplatin-based chemotherapy induces extravasated platelet aggregation in the liver. AB - Oxaliplatin-based chemotherapy plays a central role in the treatment of patients with colorectal liver metastasis (CRLM). This treatment, however, has been associated with hepatic sinusoidal obstruction syndrome (SOS), a clinically important adverse effect characterized by a bluish hue of the liver, splenomegaly and thrombocytopenia, resulting in liver dysfunction. The significant association between the sinusoidal endothelium and platelets has suggested that oxaliplatin based chemotherapy affects platelets in the liver. This study compared platelet counts in patients who did and did not receive oxaliplatin-based neoadjuvant chemotherapy (NAC). The peripheral blood platelet count was significantly lower in the NAC group (n=17) compared to that in the non-NAC, or control group (n=15) (P<0.05). The spleen index was also higher in the NAC group, although the difference was not significant. However, the spleens of the patients in the NAC group were significantly enlarged following treatment (P<0.01). Immunostaining for the platelet surface marker CD42b (glycoprotein Ib), revealed more platelets in the liver in the NAC compared to the control group, particularly in the centrilobular zone III, adjacent to the hepatic central vein and in contact with hepatocytes (P<0.01). The platelets present in the spaces of Disse, referred to as extravasated platelet aggregation (EPA), secrete a number of growth factors, including transforming growth factor-beta, vascular endothelial growth factor-A, plasminogen activator inhibitor-1 and thromboxane A2. In conclusion, EPA may play an important role in the development of hepatic SOS. Moreover, antiplatelet drugs may prevent the onset of SOS and hepatic injury in patients treated with oxaliplatin-based chemotherapy for CRLM. PMID- 26137267 TI - A prospective clinical trial of radiofrequency ablation for pulmonary metastases. AB - Pulmonary oligometastases can be treated by local treatment options, such as resection, radiofrequency ablation (RFA), and radiotherapy, in selected patients. In the present study, 67 patients with 115 pulmonary metastases were treated, and all the lesions were treated by RFA and followed with a computed tomography scan. The local control, overall survival (OS), progression-free survival (PFS) and treatment-related toxicity were observed. Median follow-up duration after the initial RFA was 24 months (range, 3-39 months). The median PFS from RFA was 14 months [95% confidence interval (CI), 11.6-16.4]. The 6-, 12- and 18-month PFS rates were 82.1, 55.7 and 27.5%, respectively. The median OS rate from RFA was 24 months (95% CI, 18.2-29.8). The 1-, 2- and 3-year OS rates were 83.6, 46.3 and 14.3%, respectively. Primary tumor was significantly correlated to PFS and OS on multivariate analysis, and other variates showed no significance. Therefore, RFA is safe for patient treatment and can be considered as a promising treatment option for patients with pulmonary metastases. PMID- 26137268 TI - The combination of the expression of hexokinase 2 and pyruvate kinase M2 is a prognostic marker in patients with pancreatic cancer. AB - Metabolism may determine the biologically malignant behavior of pancreatic cancer. To investigate the significance and prognostic value of cancer metabolism in cancer patients, we investigated the expression of two key enzymes in anaerobic glycolysis, hexokinase 2 (HK2) and pyruvate kinase isoenzyme type M2 (PKM2), in surgical specimens obtained from 36 patients who underwent curative resection of pancreatic ductal carcinoma. The hk2-glycolysis axis is a key system in the clinical imaging of tumors via positron emission tomography. Immunohistochemical staining for hk2 and pkm2 was performed and the data were statistically analyzed to evaluate their prognostic power. The expression of hk2 and pkm2 was associated with clinicopathological variables and patient prognosis, including overall survival, local recurrence-free survival and distant metastasis free survival. Staining for hk2 was negative and positive in 42 and 58% of the patients, respectively, whereas staining for pkm2 was negative and positive in 56 and 44%, respectively; hk2-positive staining was correlated with progressive pathological tumor stage (pT3 vs. pT1 and pT2; P=0.017). In the univariate analysis, the positive expression of hk2 and pkm2, pathological stage (pT3 vs. pT1 and pT2) and nodal metastasis were significantly correlated with poor prognosis (P<0.03). In the multivariate analysis, pathological nodal metastasis was an independent prognostic factor for overall survival, whereas the positive expression of hk2 and pkm2 exhibited borderline significance (P=0.08 and 0.12, hazard ratio = 2.57 and 2.16, respectively). In addition, the combination of high expression of hk2 as well as pkm2 was found to be significant (P<0.05). These results suggested that the expression of hk2 and pkm2, particularly their combination, in surgical specimens obtained during curative resection, may predict an unfavorable clinical outcome in patients with pancreatic cancer. PMID- 26137269 TI - Insulin-like growth factor 1 receptor expression in breast cancer tissue and mammographic density. AB - The aim of this study was to evaluate the association between insulin-like growth factor 1 receptor (IGF-1R) expression in breast cancer tissue and mammographic density and the clinical significance of IGF-1R overexpression. A total of 167 patients with primary invasive breast cancer were analyzed. Mammographic breast density and IGF-1R overexpression were correlated with clinicopathological parameters and analyzed by overall survival (OS) and disease-free survival (DFS). Increased breast tissue density was significantly associated with age, body mass index, menopausal status, histological grade and IGF-1R overexpression in the univariate analysis and with age (P=0.001), histological grade (P=0.045) and IGF 1R overexpression (P=0.021) in the multivariate analysis. IGF-1R overexpression was significantly associated with dense breast tissue in patients aged >40 years (P=0.002). IGF-1R overexpression in breast cancer in premenopausal women was associated with human epidermal growth factor receptor 2 (HER-2) positivity (P=0.016) and worse DFS (P=0.0414). There was no significant difference in OS and DFS between dense and non-dense breast tissue. IGF-1R expression in breast cancer tissue was significantly associated with mammographic breast tissue density in patients aged >40 years. It appears that IGF-1R expression in breast cancer tissue plays an important role in breast cancer in patients with dense breast tissue. In premenopausal women, IGF-1R overexpression in breast cancer tissue was significantly associated with HER-2 positivity and poor DFS. PMID- 26137270 TI - Clinical value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in evaluating relapsed and refractory nasopharyngeal carcinoma: A case report. AB - For patients with locoregionally advanced nasopharyngeal carcinoma (NPC), radiotherapy, chemotherapy and even targeted therapy are widely accepted treatments. These treatments, although they mostly achieve locoregional tumor control, they may also be associated with complex post-treatment changes, such as edema, loss of tissue planes, fibrosis, mucositis and scarring, which may interfere with the detection of local recurrence and the response to therapy. However, timely detection is crucial for deciding whether treatment modification or discontinuation is required. This is the case report of A 51-year-old nasopharyngeal carcinoma patient with cervical nodal metastases (CNM). Following radiotherapy, chemotherapy and targeted therapy, multislice spiral enhanced computed tomography (CT), enhanced magnetic resonance imaging (MRI) and 18F fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT of the neck were performed to compare the extent of the CNM. The enhanced CT and MRI images were unremarkable, whereas the 18F-FDG PET/CT images revealed the exact recurrence or remission. Therefore, 18F-FDG PET/CT exhibits a better sensitivity and specificity for evaluating the response to combined treatment compared to CT and/or MRI. PMID- 26137271 TI - Diagnostic and prognostic significance of glypican 5 and glypican 6 gene expression levels in gastric adenocarcinoma. AB - Gastric Cancer is one of the most common malignancies worldwide and the second most common cause of cancer-related mortality. Previous studies revealed several genetic alterations specific to gastric cancer. In this study, we aimed to investigate the diagnostic and prognostic significance of the expression levels of the glypican 5 and glypican 6 genes (GPC5 and GPC6, respectively) in gastric cancer. For this purpose, GPC5 and GPC6 expression was quantitatively determined by quantitative polymerase chain reaction method in normal gastric mucosa and intestinal type gastric adenocarcinoma samples from 35 patients. The expression levels of GPC5 and GPC6 were compared between normal and tumor tissues. Additionally, the association of the expression levels in tumor tissues with several clinicopathological parameters was evaluated. Although GPC5 was not expressed in any of the samples, the expression of GPC6, which was detected in both groups, was found to be significantly higher in tumor tissues compared to that in normal samples (P=0.039). However, there was no statistically significant association between GPC6 expression and any of the clinicopathological parameters investigated (P>0.05). Our findings suggested that an increase in GPC6 expression levels may be implicated in gastric cancer development, but not in cancer progression. PMID- 26137272 TI - Circulating antibodies to p16 protein-derived peptides in breast cancer. AB - Overexpression of the p16 protein has been reported in breast cancer and may trigger the secretion of antibodies against itself. Circulating anti-p16 antibodies that were detected with a recombinant protein have been reported in breast cancer. The present study was designed to determine whether the levels of circulating IgG antibody to p16 protein-derived linear antigens are altered in breast cancer. An enzyme-linked immunosorbent assay (ELISA) was developed in house to determine circulating IgG against peptide antigens derived from the p16 protein in 152 female breast cancer patients and 160 healthy female subjects. The Student's T-test revealed that breast cancer patients exhibited significantly higher levels of anti-p16 IgG antibody compared to control subjects (T=2.02, P=0.045). In addition, ductal cancer appeared to be the main type contributing to the increased levels of circulating anti-p16 antibodies (T=2.08, P=0.038). Of all four stages of breast cancer, stage I was associated with the highest levels of IgG antibody (T=2.02, P=0.045) and receiver operating characteristic (ROC) analysis demonstrated that the area under the ROC curve was 0.74 (95% confidence interval: 0.65-083) and that the sensitivity against a specificity of 90% was 30.3%. Therefore, the levels of circulating IgG antibody to the p16 protein may be a potential biomarker for early diagnosis of breast cancer. PMID- 26137273 TI - Diagnostic relevance of autoantibody detection against inhibitors of apoptosis proteins in colon cancer and colon adenoma. AB - Autoantibodies against cancer-related antigens may be detected in the sera of patients with various types of cancer, although their clinical utility has not yet been established. In this study, we aimed to demonstrate the diagnostic relevance of autoantibody detection against inhibitor of apoptosis protein (IAP) family members in colon cancer, as compared to anti-p53 antibody, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9. We established an ELISA system using original recombinant proteins of IAP family members (survivin, livin and X-linked IAP) and measured the expression levels in the sera of 62 healthy donors, 250 patients with colon polyps (adenoma) and 176 patients with colon cancer. When the cutoff value was set as the mean value + 2 standard deviations in healthy donors, anti-survivin exhibited the highest positivity rate (24.4%) among IAP autoantibodies in cancer patients. Furthermore, the anti survivin antibody exhibited a high positivity rate in early-stage carcinoma and adenoma. In the combination assay, reflecting the significantly high positivity rate of CEA in stage IV tumors, the positivity rate was highest when combining the detection of anti-survivin antibody and CEA in cancer patients (50.0%), indicating that this combination may not be useful for the diagnosis of early stage cancers. By contrast, reflecting the complete independencE of anti-survivin and anti-p53 antibodies, the combination of detecting these two antibodies resulted in the highest positivity rate (35.6%) in early-stage disease (stage 0 I). These results suggest that the combined measurement of anti-survivin and anti p53 antibodies may be useful for the detection of early-stage colon cancer. PMID- 26137274 TI - Prognostic outcome in patients treated with tyrosine kinase inhibitors as first line molecular-targeted therapy for metastatic renal cell carcinoma: Experience in real-world clinical practice in Japan. AB - The aim of this study was to evaluate the oncological efficacy of tyrosine kinase inhibitors (TKIs) as first-line molecular-targeted therapy for Japanese patients with metastatic renal cell carcinoma (mRCC) in a routine clinical setting. This study included a total of 271 consecutive Japanese patients with TKI-naive mRCC, including 172 patients who received sorafenib and 99 who received sunitinib for >=2 months as a first-line molecular-targeted agent. The prognostic outcomes of these patients were retrospectively assessed. During the observation period (median, 19 months), 126 patients (46.5%) succumbed to the disease and the median overall survival (OS) for the entire cohort was 33.1 months. The univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, histological subtype and sarcomatoid characteristics as significant predictors of OS. Of these factors, only the MSKCC classification, CRP level and liver metastasis were found to be independently associated with OS in the multivariate analysis. Furthermore, there were significant differences in OS according to the positivity for these 3 independent risk factors (i.e., negative for all factors vs. positive for a single factor vs. positive for 2 or 3 factors). These findings suggest that the introduction of TKIs as first-line molecular-targeted agents resulted in favorable cancer control outcomes in Japanese mRCC patients and that the prognosis of these patients may be stratified by 3 potential parameters, including the MSKCC classification, CRP level and liver metastasis. PMID- 26137275 TI - Clinicopathological characteristics and prognosis of breast cancer patients with type 2 diabetes mellitus. AB - Type 2 diabetes mellitus (T2DM) can increase the risk of several common cancers, including breast cancer (BC). The purpose of the present study was to investigate the clinicopathological features and prognosis of BC patients with or without T2DM. Seventy-eight patients were diagnosed with T2DM prior to the diagnosis of BC in the Cancer Hospital of Shantou University Medical College (Shantou, China) between 2002 and 2008. A total of 300 BC patients without T2DM were randomly selected as study controls during the same period. The clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) rates of these two groups were compared. Fifty-five BC patients and 133 control patients with T2DM were >50 years old (70.5 and 44.3%, respectively). There were more T2DM BC patients with body mass index (BMI) >=25 kg/m2 (46.2 vs. 23.3%) and these patients had a higher rate of lymph node involvement (67.9 vs. 55.0%). The DFS of the two groups was 32.1 vs. 22.3%. The OS of the two groups was 24.4 vs. 13.7%. Following adjustment for BMI, tumor-node metastasis stage and stratification of age, the relapse risk of T2DM BC patients was >2-fold higher than that of the control group in the estrogen receptor/progesterone receptor (ER/PR)-positive patients. In Her-2-negative BC patients, the relapse risk of T2DM patients was 2.237-fold higher than that of the non-T2DM patients. In conclusion, T2DM BC patients were significantly older and more likely to be overweight, and had more lymph nodes involvement. T2DM was associated with poor prognosis in ER/PR positive or Her-2-negative BC patients. PMID- 26137276 TI - Tea consumption and risk of gallbladder cancer: A meta-analysis of epidemiological studies. AB - Previous epidemiological studies investigating the association between tea consumption and the risk of gallbladder cancer have yielded inconsistent results. Therefore, we aimed to assess this association by conducting a meta-analysis of all available studies. A search was conducted through Pubmed, Embase, Chinese Biomedical literature Database and China Knowledge Resource Integrated Database to identify relevant studies on tea consumption and the risk of gallbladder cancer. A random-effects model was used to calculate the overall combined risk estimates. Six studies (4 case-control and 2 cohort studies), involving a total of 753 patients and 115,349 controls, were included in this meta-analysis. The overall combined odds ratio (OR) for tea consumption and gallbladder cancer was 0.67 [95% confidence interval (CI): 0.40-1.12, P=0.13]. Similar results were obtained for the high or moderate tea consumption vs. the low/non-consumption groups. However, our meta-analysis identified a significant association between tea consumption and reduced gallbladder cancer risk in women (OR=0.46, 95% CI: 0.26-0.81, P=0.008), but not in men (OR=0.43, 95% CI: 0.12-1.59, P=0.21). Therefore, the results of the present meta-analysis suggest that, according to the currently available epidemiological studies, tea consumption may reduce the risk of gallbladder cancer in women, but not in men. Further epidemiological studies are required to determine the association between tea consumption and the risk of gallbladder cancer. PMID- 26137277 TI - Comparison of surgical techniques for stoma closure: A retrospective study of purse-string skin closure versus conventional skin closure following ileostomy and colostomy reversal. AB - The aim of this study was to compare the incidence of postoperative complications, including superficial incisional surgical site infection (SSI) following purse-string skin closure (PS) and conventional skin closure with a drainage tube (CD) following stoma closure. A total of 55 consecutive patients who underwent loop colostomy and loop ileostomy closures in our hospital between October, 2011 and September, 2014 were retrospectively assessed. The patients were divided into two groups, namely the PS group (26 patients) and the CD group (29 patients). There were no significant differences in the characteristics of the patients between the two groups. The baseline and operative characteristics also did not differ significantly between the two groups. However the incidence of superficial incisional SSI was lower in the PS group compared to that in the CD group (0 vs. 13.8%, respectively; P=0.049). The overall incidence of complications did not differ significantly between the two groups (P=0.313). The duration of postoperative hospital stay in the PS group was shorter compared to that in the CD group. In conclusion, the results of this study suggest that PS may an effective technique to reduce the incidence of superficial incisional SSI. This technique appears to be superior to the conventional technique, allowing for better cosmesis. PMID- 26137278 TI - Association of circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 with the risk of ovarian cancer: A systematic review and meta-analysis. AB - Insulin-like growth factor 1 (IGF-1) and its main binding protein (IGFBP-3) in blood have been associated with the risk of several types of cancer. However, epidemiological studies have inconsistent results regarding the association of circulating IGF-1/IGFBP-3 levels with ovarian cancer risk. A systematic review of the prospective studies was conducted using meta-analysis to evaluate the existing evidence. Pubmed and Embase databases were searched to identify the relevant studies published before May 1, 2014. Four highly qualified studies with a total of 627 cases and 1,358 controls were finally included in the meta analysis. Random effects meta-analysis was conducted by combining study-specific odds ratios (ORs) of ovarian cancer for the highest verses lowest exposure levels. A dose-response association was further assessed by relating the log of ORs for different exposure levels. As a result, the pooled ORs for the highest verses lowest categories of IGF-1/IGFBP-3 were 0.85 [95% confidence interval (CI), 0.51-1.40]/0.78 (95% CI, 0.43-1.40). In the subgroup analyses, the pooled ORs of IGF-1/IGFBP-3 were 1.89 (95% CI, 0.64-5.59)/1.08 (95% CI, 0.50-2.32) for the subgroup with cases diagnosed at <55 years, and 0.74 (95% CI, 0.50-1.08)/0.98 (95% CI, 0.73-1.33) for the subgroup with cases diagnosed at >=55 years. No linear association between circulating IGF-1/IGFBP-3 levels and ovarian cancer risk was identified. As no significant association of IGF-1/IGFBP-3 with ovarian cancer risk was identified in the present meta-analysis of existing studies, more studies with greater quality are required in the future. PMID- 26137279 TI - Antithyroid peroxidase antibody positivity is associated with lower incidence of metastasis in breast cancer. AB - Thyroid extracts were first used to treat patients with metastatic breast cancer over a century ago. Since then, a number of studies have investigated the association between thyroid disorders and breast cancer. The presence of antibodies to thyroid peroxidase (TPOab) was recently reported to be associated with improved outcome in these patients. The aim of the present study was to evaluate the association between TPOab positivity and clinicopathological characteristics in breast cancer patients. The study included 318 newly diagnosed cases of breast cancer treated at Ondokuz Mayis University Hospital, Samsun, Turkey, between 2008 and 2012. Serum thyroid-stimulating hormone, free triiodothyronine and free thyroxine levels were measured at the time of diagnosis. Of the 318 patients, 253 were considered to be TPOab-negative (TPOab <=34 IU/ml) and 65 TPOab-positive (TPOab >34 IU/ml). No cases with distant metastases were found in the TPOab-positive group. However, 20 (7.9%) of the 253 patients displayed distant metastases in the TPOab-negative group (P=0.01). Therefore, TPOab positivity was found to be associated with a lower incidence of metastasis in breast cancer patients. PMID- 26137280 TI - Prognostic significance of osteopontin expression in non-small-cell lung cancer: A meta-analysis. AB - Osteopontin (OPN) plays an important role in the progression and metastasis of cancer. However, the role of OPN as a prognostic factor in non-small-cell lung cancer (NSCLC) remains controversial. The aim of this study was to investigate the association between OPN expression and prognosis in patients with NSCLC using a meta-analysis. Based on PubMed, Ovid Medline, Embase, ISI, ScienceDirect and SpringerLink databases, related articles published prior to January, 2013 were collected. A meta-analysis was conducted to investigate the association of OPN expression with overall survival (OS) and progression-free survival (PFS) in patients with NSCLC. Hazard ratio (HR) with 95% confidence interval (CI) was used to assess the strength of this association. A total of 6 studies, including 776 patients, were found to be eligible for the meta-analysis. No heterogeneity was observed in OS or PFS, whereas low OPN expression was found to be correlated with better OS (HR=0.57, 95% CI: 0.46-0.70) and PFS (HR=0.62, 95% CI: 0.49-0.77). This meta-analysis demonstrated an association of OPN with poor prognosis in NSCLC patients. However, prospective studies are required to confirm these findings. PMID- 26137281 TI - Association between folate metabolism-related polymorphisms and colorectal cancer risk. AB - Folate has essential roles in DNA synthesis, repair and methylation. Folate metabolism-related gene variants may modulate the levels of this vitamin and affect the cancer risk. Thus, whether these polymorphisms play an important role in carcinogenesis, particularly colorectal cancer (CRC) development, has been a subject interest. The present study investigated the association between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS) and the reduced folate carrier 1 (RFC1) genes and CRC risk. Polymorphisms in MTHFR (677C>T and 1298A>C), TS [1494del6 and the TS enhancer region (TSER)] and RFC1 (-43T>C, 80G>A and 696C>T) were characterized using polymerase chain reaction-restriction fragment length polymorphism in 477 CRC cases and 514 controls. Although no polymorphisms were significantly associated with the CRC risk in the overall sample, significant associations between folate metabolism-related polymorphisms and CRC risk were identified in the stratified analyses. The MTHFR 677CT/1298AC and MTHFR 1298AC+CC/TSER 2R3R genotypes in the presence of plasma folate levels <=4.12 ng/ml were associated with significantly increased CRC risk. In addition, individuals with the MTHFR 677TT/TSER 3R3R or MTHFR 677/TSER 3R3R/TS 1494 0bp6bp+6bp6bp genotypes and diabetes mellitus (DM) were at an increased risk for CRC. Therefore, the data suggest that i) MTHFR polymorphisms combined with low plasma folate levels and ii) polymorphisms in folate metabolism-related genes combined with metabolic syndrome risk factors (hypertension and DM) increase the odds of developing CRC. PMID- 26137282 TI - Association of the XPA A23G polymorphism with the risk of head and neck carcinomas: Evidence from 5,491 subjects. AB - The XPA gene participates in modulating DNA damage recognition during the DNA nucleotide excision repair process. Current data regarding the association of the XPA A23G polymorphism with the risk of head and neck squamous cell carcinoma (HNSCC) remain controversial, and meta-analyses focusing on the HNSCC risk and this polymorphism are limited. Therefore, the aim of the present study was to derive a more precise estimation of this association by a meta-analysis of all the eligible studies. Odds ratios (ORs) with 95% confidence intervals (CI) were assessed for the strength of the associations in eight studies, including 5,491 subjects (2,409 HNSCC cases and 3,082 controls). The overall analysis revealed that the XPA A23G polymorphism was not significantly associated with the overall HNSCC risk. Consistently, there was no evidence for the association between the XPA A23G polymorphism and HNSCC risk in subgroup analyses based on ethnicity and the source of controls. However, the significant associations in oral carcinoma with the increased risk among the XPA heterozygote (AG vs. AA: OR, 1.58; 95% CI, 1.06-2.37; Pheterogeneity=0.23, I2=30%) and dominant (AG +GG vs. AA: OR, 1.53; 95% CI, 1.04-2.23; Pheterogeneity=0.21, I2=36%) models were observed in the subgroup analysis by tumor site. In conclusion, the meta-analysis suggested that the XPA A23G polymorphism was not associated with overall HNSCC susceptibility, but it was associated with oral carcinoma susceptibility and it may be a risk factor for oral carcinoma. Further well-designed and large studies are required to confirm these associations. PMID- 26137283 TI - Rapid and early alpha-fetoprotein and des-gamma-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma. AB - The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in alpha-fetoprotein (AFP) and des gamma-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5 fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects. PMID- 26137284 TI - Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: A systematic review and meta-analysis. AB - The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins >=1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23-0.64]. The absolute risk difference was 10.1% (95% CI: 4.9-17.6), corresponding to a number needed to treat of 10. Our pooled meta analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: 0.10-0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: -0.28-1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS. PMID- 26137285 TI - Outcome of papillary thyroid microcarcinoma: Study of 1,990 cases. AB - The present study examines the requirement of prophylactic neck node dissection in papillary thyroid microcarcinoma (PTMC) patients by analyzing high-risk factors of neck lymph node metastasis in PTMC. The clinical pathological data was a review of 1,990 patients diagnosed between January 2013 and January 2014. The data included information on patient gender, age, tumor size, multifocal, tumor pathological staging, bilateral thyroid cancer, the subtypes, BRAFV600E mutation, human telomerase reverse transcriptase (hTERT), extrathyroidal invasion and neck lymph node metastasis. The univariate analysis (chi2 test) showed that a number of factors were significantly associated with neck lymph node metastasis in PTMC (P<0.05): Male gender, aged <45 years, extrathyroidal invasion, bilateral thyroid cancer, various subtypes (package type, follicular variant, diffuse sclerosing variant, eosinophils, tall cell and column variant), BRAFV600E mutation-positive, hTERT mutation-positive, pt3/4 and multifocality. The multivariate analysis (regression binary logistic) showed that the male gender, <45 years, tumor size >5 mm, extrathyroidal invasion, bilateral thyroid tumors, multifocality, BRAFV600E mutation-positive, hTERT mutation-positive and pt3/4 are associated with the neck lymph node metastasis in PTMC (P<0.05). These paired analysis results show that the subtypes of PTMC with tumor size >5 mm is more common than the specific types of PTMC in which the tumor is <=5 mm in neck lymph node metastasis. The neck lymph node metastasis incidence of the >45 years age group patients without high-risk factors in PTMC is 8.13 and 6.80%, respectively. In conclusion, PTMC patients with high-risk factors only are recommended to undergo a prophylactic lymph node dissection. PMID- 26137286 TI - Periosteal chondroma of the distal tibia: Computed tomography and magnetic resonance imaging characteristics and correlation with histological findings. AB - Periosteal chondroma is a rare benign hyaline cartilage neoplasm situated on the bone surface. This is the presentation of a unique case of periosteal chondroma arising in the left distal tibial metaphysis of a 25-year-old female patient with a history of antecedent trauma. The physical examination revealed swelling and tenderness in the anterolateral aspect of the left distal lower limb. Plain radiographs revealed a discernible soft tissue lesion with peripheral foci of mineralization. Computed tomography scans confirmed the presence of a surface based mass with peripheral ossification and a thin rim of calcification. On magnetic resonance imaging, the well-circumscribed mass exhibited intermediate signal intensity on T1-weighted sequences and high signal intensity with foci of decreased signal intensity on T2-weighted sequences. Contrast-enhanced T1 weighted sequences revealed predominantly peripheral enhancement without intramedullary involvement. Following an open biopsy, marginal excision with curettage of the underlying bone cortex was performed. Histologically, the tumor consisted of mature hyaline cartilage arranged in distinct lobules. Foci of ossification with mature bone trabeculae forming a thin shell-like structure were identified in the periphery of the tumor. The mindbomb E3 ubiquitin protein ligase 1 labeling index was <1%. Based on these findings, the tumor was diagnosed as periosteal chondroma. There has been no evidence of local recurrence at 4 months following surgery. Despite its rarity, periosteal chondroma must be considered as a possible diagnosis when confronted with a surface-based, mineralized lesion in the metaphysis of long bones. PMID- 26137287 TI - Comparison of two different standards of care in detecting malignant thyroid nodules using thyroid fine-needle aspiration. AB - The aim of the present study was to verify the optimal method to obtain enough fine-needle aspiration (FNA) materials for detecting thyroid malignancy. A prospective study was performed by comparing two different regional standards of care. In one group a traditional FNA method mainly used in Asian countries, including China, was performed in which a single pass of a 22-G needle was applied with or without aspiration. In the other group, the method mainly used in Western countries was performed in which three passes of a 25-G needle with non aspiration were undertaken for thyroid nodules. The study included 718 thyroid nodules from 695 patients. These nodules were allocated for three different methods of performing thyroid FNA. There were 332 thyroid nodules subjected to the traditional Asian FNA method using a 22-G needle with aspiration for 142 nodules and non-aspiration for 190 nodules. FNA using the Western method was performed with three passes of non-aspiration using 25 G for 386 nodules. All the FNAs were performed with the guidance of ultrasound. The components of the nodules were documented. All the samples were reported using the Bethesda System for Reporting Thyroid Cytopathology. Among the 22 G group, the non-diagnostic rate in the aspiration group was as high as 76.76%, which was significantly higher than 44.21% in the non-aspiration group (P<0.01). For the non-aspiration group, the non-diagnostic rate in the 25 G group was 34.97%, which was significantly lower than 44.21% in the 22 G group. In general, the non-diagnostic rate for the 25-G needle was 34.97%, which was significantly lower than 58.13% in all the 22 G groups. For the solid and mixed nodules, the non-diagnostic rate was lower in the 25-G needle group compared to the 22 G groups with statistical significance. The non-aspiration method using a 25-G needle with multiple passes can result in a higher diagnostic rate for thyroid FNA. PMID- 26137288 TI - Phase II trial of concurrent chemoradiotherapy with S-1 versus weekly cisplatin for locoregionally advanced nasopharyngeal carcinoma. AB - This is a prospective randomized trial performed to compare the efficacy of concurrent chemoradiotherapy (CCRT) + S-1 (oral fluoropyrimidine) with that of CCRT + cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 105 eligible patients were randomly assigned to receive CCRT with S-1 (S-1 arm, n=50) or cisplatin weekly (control arm, n=55). Patients in the S-1 arm received CCRT plus S-1 (40-60 mg, twice daily for 4 consecutive weeks. Patients in the control arm received standard CCRT with weekly cisplatin. All the patients were included in an intention-to-treat survival analysis. Our results demonstrated that the S-1 and control arms did not differ significantly in terms of complete response, partial response, progression-free survival or overall survival (all P-values >0.05). However, the two arms varied significantly regarding certain grade 3-4 toxicities, including leukopenia, 5.5 vs. 22.0% (P=0.013); mucositis, 20.0 vs. 46.0% (P=0.004); dermatitis, 15.5 vs. 32.7% (P=0.011); and nausea, 9.1 vs. 41.6% (P<0.001) for the S-1 and control arms, respectively. In conclusion, CCRT with S-1 was found to be similar in efficacy but superior in terms of toxicity compared to the standard CCRT with weekly cisplatin. PMID- 26137289 TI - Predictive factors of cytotoxic damage in radioactive iodine treatment of differentiated thyroid cancer patients. AB - Radioactive iodine (131I) therapy in patients suffering from differentiated thyroid cancer (DTC) is a targeted treatment commonly used for thyroid ablation and locoregional and distant metastatic spread management. Despite a significant proportion of the 131I dose entering the circulation, there is currently no detailed information regarding its effect on the blood cell system. In order to assess the cytotoxic effects of 131I therapy on the circulatory system, blood cell levels, thyroid-related hormones and CD45+ cell cytotoxicity were estimated in blood collected from patients with DTC. The micronuclei (MN) frequency of the peripheral blood CD45+ cell fraction was significantly increased after 30 days of 131I therapy compared to that prior to treatment, although a strong individual variation was observed. A significantly negative correlation between MN frequency and the level of platelets and plateletcrit was observed; however, there was no such correlation with thyroid-related hormones. These resultS suggest that the correlation between MN frequency and the platelet system may serve as a biomarker of exposure and, possibly, of sensitivity in DTC patients undergoing 131I therapy following thyroid and lymph node surgery. PMID- 26137290 TI - Microsatellite instability and survival in gastric cancer: A systematic review and meta-analysis. AB - Microsatellite instability (MSI) is associated with the prognosis in several cancers and is used for determination of the chemotherapy regimen in stage II colon cancer in the National Comprehensive Cancer Network guideline. However, the association between MSI and the prognosis of gastric cancer remains unclear. PubMed database was searched until January 2014 using MeSH terms and key words to identify the studies evaluating MSI and prognosis of gastric cancer and the references were manually searched. The main outcome was the overall survival rate and the subordinate outcome was the association between high-frequency MSI (MSI H) and clinicopathological characteristics. Eight studies met the inclusion criteria and the majority of data were collected retrospectively. There were 1,976 patients, 431 of which were MSI-H patients, with a range of 11.68-33.82%. Four studies used the National Cancer Institute panel to define MSI-H, the other four had microsatellite markers ranging 2-11. Significant associations were found in three studies and the overall summary estimate was hazard ratio, 0.63 (95% confidence interval, 0.52-0.77), with no evidence of inter-study heterogeneity (I2=0.0%). MSI-H patients were identified to have a tendency to have less lymph node (LN) metastasis, superficial tumor invasion and to be intestinal type. In conclusion, MSI-H gastric cancers have an improved prognosis, accompanied with reduced risk of LN metastasis, tumor invasion and mortality. PMID- 26137291 TI - Lower lobe origin is a poor prognostic factor in locally advanced non-small-cell lung cancer patients treated with induction chemoradiotherapy. AB - The AIM of this study was to identify prognostic factors in patients receiving trimodality therapy for locally advanced non-small-cell lung cancer (NSCLC). Among patients who underwent induction chemoradiotherapy (CRT) followed by surgery between 1999 and 2011 at our institution, 76 NSCLC patients with clinical (c) N2/3 stage III were enrolled in this retrospective study. Induction CRT consisted of docetaxel and cisplatin with concurrent 40-60 Gy radiation therapy. In total, 76 patients were assessed (53 men and 23 women) with 43 adenocarcinomas and 33 non-adenocarcinomas. Of the 76 patients, 44 had cStage IIIA and 32 had cStage IIIB disease. The primary tumors were located in the right upper lobe (N=33), right middle lobe (N=5), right lower lobe (N=11), left upper lobe (N=20s) and left lower lobe (N=7). For all 76 patients, lower lobe tumors were associated with a significantly shorter overall survival (OS) and disease-free survival (DFS) compared to non-lower lobe tumors (OS, P=0.022; and DFS, P=0.0007). When the analysis was limited to pathologically proven N2/3 disease prior to induction CRT (n=36), lower lobe location, compared to other locations, tended to be a poor prognostic factor (OS, P=0.068; and DFS, P=0.0075). Our results indicated that a lower lobe tumor origin is associated with unfavorable prognosis in NSCLC patients treated with induction CRT, strongly suggesting the significance of appropriate patient selection in order to maximize the benefits of trimodality therapy. PMID- 26137292 TI - Decreased mRNA expression of transcription factor forkhead box F2 is an indicator of poor prognosis in patients with resected esophageal squamous cell carcinoma. AB - The transcription factor forkhead box F2 (FOXF2) is an evolutionarily conserved DNA-binding protein involved in embryogenesis and metabolism. Although recent studies prove that FOXF2 is a tumor suppressor in various human cancers, the role of FOXF2 in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, samples were collected from 188 ESCC patients, including 33 pairs of tumor and non-tumor tissues, and FOXF2 mRNA expression was investigated by quantitative polymerase chain reaction. The results demonstrated that FOXF2 mRNA is downregulated in tumor tissues compared to paired non-tumor tissues (P=0.048). The receiver operating characteristic curve analysis indicated 1.2 as a cut-off point and, thus, 125 and 63 tumors were classified as low- and high-level FOXF2 mRNA expression, respectively. We observed that low-level FOXF2 mRNA expression in the tumors was associated with a higher frequency of lymph node metastasis (P=0.044), an effect further suggested by the multivariate logistic regression analysis (P=0.060). According to the univariate Cox analysis, patients harboring tumors with low-level FOXF2 mRNA expression had a significantly increased mortality risk compared to those with high-level expression (hazard ratio=1.700, 95% confidence interval, 1.077-2.681), with 5-year survival rates of 41.1 and 61.9%, respectively. This negative prognostic effect of low-level FOXF2 mRNA expression was further validated in the multivariate Cox analysis (P=0.021). The subgroup analysis demonstrated that the effect of FOX2 mRNA expression was limited to male patients and those with advanced-stage disease. Taken together, these findings suggest that FOXF2 may be an anti-oncogene for ESCC and decreased FOXF2 mRNA expression is associated with a poor prognosis in patients with ESCC. PMID- 26137293 TI - Platinum-based therapy for triple-negative breast cancer treatment: A meta analysis. AB - The aim of the present study was to evaluate the effect of platinum-based therapy on the short-term efficacy and survival rate in patients with triple-negative breast cancer (TNBC). A search of available databases was conducted, based on specific inclusion and exclusion criteria, for trials conducted between January 2006 and January 2014. The bibliographies of the included studies were examined with the same criteria. Included studies were evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE), and extracted data were analyzed using RevMan 5.1 and GRADEprofiler 3.6. Eight studies with a total of 1,349 patients were included. The meta-analysis revealed that the pathological complete response rate and overall response rate in TNBC patients who were treated with a platinum-based regimen was significantly higher than that in those treated with a non-platinum-based regimen (49.2 and 64.3%, respectively). The disease-free survival rate and overall survival rate were not significantly different between TNBC patients treated with a platinum-based regimen and those treated with a non-platinum-based regiment (P>0.05). Platinum based chemotherapy in TNBC patients resulted in improved short-term efficacy. Platinum-based regimens may therefore be more sensitive to TNBC patients. However, future multicenter randomized controlled trials are required to validate these findings and to determine whether platinum-based chemotherapy can extend the survival rate of TNBC patients. PMID- 26137294 TI - Epidemiology and characteristics of febrile neutropenia in oncology patients from Spanish tertiary care hospitals: PINNACLE study. AB - Febrile neutropenia (FN) is one of the most common adverse events associated with myelosuppressive chemotherapy for cancer treatment. The objective of this study was to describe the incidence of hospitalization due to FN in Spanish tertiary care hospitals (PINNACLE study). This epidemiological, retrospective, multicenter, nationwide study involved 119 patients from oncology units of 10 Spanish tertiary care hospitals who were admitted for FN. The primary endpoint was to assess the epidemiology and characteristics of FN. The incidence of admissions due to FN in oncology patients was 2.0% (interquartile range [IQR], 1.6-3.0). In terms of fever and absolute neutrophil count (ANC), 37.0% of the patients had a temperature of >=38.2 degrees C and an ANC of <=500/m3. The number of patients who received prophylactic treatment with granulocyte colony stimulating factor (G-CSF) was significantly higher in the palliative group (32.6%) compared with that in the non-palliative group (13.5%). The hospital length of stay was significantly shorter in patients who received prophylactic G CSF compared with those who did not (5.0 days; IQR, 4.0-9.0 vs. 7.0 days; IQR, 5.0-11.0, respectively). The hospital length of stay was also significantly shorter in patients receiving palliative treatment (5.0 days; IQR, 3.0-7.0) compared with those receiving non-palliative therapy (7.0 days; IQR, 5.0-12.0). In conclusion, the incidence of admissions due to FN in oncology patients was 2.0% and the duration of hospital stay was 7.0 days. Prophylactic G-CSF treatment was found to be associated with better outcomes and shorter hospital stays. Therefore, the use of this treatment becomes relevant for achieving better clinical outcomes and reducing hospitalization cost in the management of FN. PMID- 26137296 TI - UEG career highlight: Rebecca Fitzgerald, winner of the UEG Research Prize 2014. PMID- 26137295 TI - On dogs, people, and a rabies epidemic: results from a sociocultural study in Bali, Indonesia. AB - BACKGROUND: Previously free of rabies, Bali experienced an outbreak in 2008, which has since caused a large number of human fatalities. In response, both mass dog culling and vaccination have been implemented. In order to assess potential community-driven interventions for optimizing rabies control, we conducted a study exploring the relationship between dogs, rabies, and the Balinese community. The objectives of this study were to: i) understand the human-dog relationship in Bali; ii) explore local knowledge, attitudes, and practices (KAPs) relating to rabies; and iii) assess potential community-driven activities to optimize rabies control and surveillance. METHODS: Conducted between February and June 2011, the study combined a questionnaire (n = 300; CI = 95 %; error margin = 5 %) and focus group discussions (FGDs) in 10 villages in the Denpasar, Gianyar, and Karangasem regencies. The questionnaire included a Likert scale to assess community knowledge and attitudes. For the knowledge assessment, three points were given for a correct answer, while wrong answers and uncertain answers were given zero points. For the attitudes assessment, three points were given for a positive answer, two points for a neutral answer, and one point for a negative answer. Respondent knowledge was categorized as good (score >40), fair (score 20 40), or poor (score <20), based on a maximum total score 60. Respondent attitudes were categorized as positive (score >26), neutral (score 13-26), or negative (score <13), based on a maximum total score of 39. Mixed-gender FGDs in each sub village (banjar) were conducted, each involving 7-15 participants to complement the questionnaire results. On a follow-up research trip in mid-2013, the data analysis was triangulated and validated using semi-structured interviews. Questionnaire data were analyzed descriptively using SPSS 17.0, while qualitative data from interviews and FGDs were analyzed manually according to accepted methods of coding and memo writing. The chi-square test was then used to analyze the statistical relationships between knowledge and attitudes of the respondents. RESULTS: Out of the total 300 respondents, most were predominantly male (82 %), Hindu (99 %), married (96 %), older than 30 years of age (9 %), and owned dogs (72 %). Dog ownership was motivated by culture, personal taste, and function, with dogs was being used as guards (85 %) and companion animals (27 %), and was sometimes related to religious or traditional obligations (2 %). Relating to their culture and local beliefs, and eventually becoming their way of life, 79 % of respondents kept free-roaming dogs. With the rabies outbreak in Bali and Western breeds becoming more popular, more responsible dog ownership (leashing, confining, regular feeding) became more acceptable and changed community perceptions on keeping dogs, even though the sustainability of this practice cannot be gauged. In addition, the economic situation posed major problems in rural areas. The level of community knowledge about rabies and its associated control programs were generally fair and community attitudes were positive. However, community KAPs still need to be improved. A total of 74 % respondents reported to have vaccinated their dogs in 2011, but only few were found to report rabid animals to livestock officers (12 %) and a significant number believed that washing a bite wound was not important (62 %). Moreover, free-roaming dog practices and discarding of unwanted female puppies still continue and possibly create difficulties for rabies elimination as these practices potentially increase the stray dog population. We identified three major sociocultural aspects with potential for community-driven interventions to optimize current rabies elimination efforts: integrating local notions of ahimsa (non-violence) into education campaigns, engaging communities through the local banjar sociopolitical system, and working with traditional legal structures to increase local compliance with rabies control. CONCLUSION: The human-dog relationship in Bali is multifaceted. Due to the uniqueness of the culture and the local beliefs, and encouraged by a socioeconomic aspect, a number of local practices were found to be constituting risk factors for continued rabies spread. Community knowledge and attitudes, which can consequently result in behavioral changes, needs to be improved across different genders, ages, educational backgrounds, and roles in the community, regardless of the individual village's experiences with rabies. Furthermore, community-driven activities based on sociocultural conditioning and community capacity at the banjar and village levels, such as public awareness activities, vaccination, dog registration, dog population management, and rapid response to dog bites, were identified as being able to complement the rabies control program in Bali. The program also needs recognition or acknowledgement from governments, especially local government as well as regular mentoring to improve and sustain community participation. PMID- 26137297 TI - Combining simple patient-oriented tests with state-of-the-art molecular diagnostics for early diagnosis of cancer. AB - Early diagnosis is an important strategy to improve outcomes from cancer. Oesophageal adenocarcinoma is an example of a cancer that presents late, with very poor outcomes, and for which the presence of the precursor lesion Barrett's oesophagus provides the opportunity to intervene at an early stage. In this review, I describe the challenges in the field and the work that we have done to devise a conceptually novel approach to early diagnosis, using a cell collection device (Cytosponge), coupled with molecular assays. This is a personal perspective in which I also describe the career pathway that led me into academic gastroenterology, and the rewards and challenges of translational research in molecular diagnostics. There are fantastic opportunities for clinicians wishing to pursue academic medicine, because it is a time when massive strides are being made in a whole number of areas; for example: imaging, sequencing technology and targeted therapies. Clinicians who can straddle the laboratory and the clinic are essential, to maximise the progress that can be made for the benefit of patients. PMID- 26137299 TI - The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases? AB - INTRODUCTION: Although long thought to be a sterile organ, due to its acid production, the human stomach holds a core microbiome. AIM: To provide an update of findings related to gastric microbiota and its link with gastric diseases. METHODS: We conducted a systematic review of the literature. RESULTS: The development of culture-independent methods facilitated the identification of many bacteria. Five major phyla have been detected in the stomach: Firmicutes, Bacteroidites, Actinobacteria, Fusobacteria and Proteobacteria. At the genera level, the healthy human stomach is dominated by Prevotella, Streptococcus, Veillonella, Rothia and Haemophilus; however, the composition of the gastric microbiota is dynamic and affected by such factors as diet, drugs and diseases. The interaction between the pre-existing gastric microbiota and Helicobacter pylori infection might influence an individual's risk of gastric disease, including gastric cancer. CONCLUSIONS: The maintenance of bacterial homeostasis could be essential for the stomach's health and highlights the chance for therapeutic interventions targeting the gastric microbiota, even if gastric pH, peristalsis and the mucus layer may prevent bacteria colonization; and the definition of gastric microbiota of the healthy stomach is still an ongoing challenging task. PMID- 26137298 TI - Use of probe-based confocal laser endomicroscopy (pCLE) in gastrointestinal applications. A consensus report based on clinical evidence. AB - BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) provides microscopic imaging during an endoscopic procedure. Its introduction as a standard modality in gastroenterology has brought significant progress in management strategies, affecting many aspects of clinical care and requiring standardisation of practice and training. OBJECTIVE: This study aimed to provide guidance on the standardisation of its practice and training in Barrett's oesophagus, biliary strictures, colorectal lesions and inflammatory bowel diseases. METHODS: Initial statements were developed by five group leaders, based on the available clinical evidence. These statements were then voted and edited by the 26 participants, using a modified Delphi approach. After two rounds of votes, statements were validated if the threshold of agreement was higher than 75%. RESULTS: Twenty-six experts participated and, among a total of 77 statements, 61 were adopted (79%) and 16 were rejected (21%). The adoption of each statement was justified by the grade of evidence. CONCLUSION: pCLE should be used to enhance the diagnostic arsenal in the evaluation of these indications, by providing microscopic information which improves the diagnostic performance of the physician. In order actually to implement this technology in the clinical routine, and to ensure good practice, standardised initial and continuing institutional training programmes should be established. PMID- 26137300 TI - Buspirone, a new drug for the management of patients with ineffective esophageal motility? AB - Ineffective esophageal motility (IEM) is the most frequently encountered esophageal motility disorder. Patients may present with a variety of symptoms, such as dysphagia, heartburn, odynophagia, and regurgitation. Over the past years, the landscape of esophageal motility testing has been revolutionized; however, our current treatment options for IEM still remain limited. Previous studies have suggested that buspirone, a serotonin receptor agonist, enhances esophageal peristalsis and lower esophageal sphincter (LES) function. Recent work provides the first evidence that buspirone may influence LES resting pressure in patients with systemic sclerosis. Future research should evaluate whether the beneficial effects of buspirone also apply to the broad clinical entity of esophageal dysphagia patients with IEM. PMID- 26137301 TI - Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: A pilot study. AB - BACKGROUND: Esophageal involvement in systemic sclerosis (SSc) carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers. AIM: We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc. METHODS: Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined. RESULTS: Esophageal hypomotility and hypotensive LES was found in 63% and 67% of patients, respectively. Demographic and clinical characteristics, including baseline manometric parameters, were comparable between groups. Resting pressure of LES increased after buspirone from 9.42 +/- 2.6 to 11.53 +/- 3.4 mmHg (p = 0.0002 by paired t-test), but not after domperidone; a trend for increase of amplitude of contractions was also observed after buspirone (p = 0.09). Comparison of the individual changes revealed that buspirone was superior to domperidone in enhancing LES pressure ( + 2.11 +/- 2.0 versus -0.45 +/- 2.3 mmHg, p = 0.006). No significant effects of either drug were noted on other examined parameters of esophageal function. CONCLUSION: The beneficial acute effect of buspirone on impaired LES function associated with SSc suggests a role of 5-HT1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted. PMID- 26137302 TI - Utility of Basophil Activation Test for monitoring the acquisition of clinical tolerance after oral desensitization to cow's milk: Pilot study. AB - OBJECTIVE: The quantification of basophil activation by flow cytometry is a useful tool for the assessment of immediate-type responses to food allergens and the prediction of clinical tolerance in food allergy patients. The aim of this study is to investigate how the analysis of allergen-induced CD63 up-regulation by flow cytometry can be effective in monitoring the acquisition of clinical tolerance by specific oral desensitization in food allergy. To our knowledge, this is the first study to examine this topic. MATERIALS AND METHODS: Three male patients affected by cow's milk allergy underwent successful oral desensitization to cow's milk. In order to monitor the acquired clinical tolerance that occurred after treatment, we performed laboratory tests for total and specific IgE, specific IgG4 and the Basophil Activation Test (BAT) both at baseline and at the end of the desensitization protocol. RESULTS: Using a fluorescent enzyme immunoassay, the comparison of specific cow's milk antibodies before and after treatment showed a decrease of specific IgE levels, without reaching normal values, and an increase of specific IgG4 levels. A complete suppression of cow's milk proteins (alpha-lactoalbumin, beta-lactoglobulin and casein) induced CD63 regulation was observed in all three reported cases. CONCLUSIONS: Using flow cytometry, food allergen-specific basophil responses could be monitored in order to identify an acquired tolerance induced by desensitization treatment. Although further studies are needed to develop this important new topic, it was interesting to note that the BAT seemed to be more sensitive and characterized by a close correlation with clinical tolerance. PMID- 26137303 TI - Management of acute variceal bleeding using hemostatic powder. AB - BACKGROUND AND OBJECTIVES: This study aimed to test the safety and efficacy of Hemospray(r) for emergency control of acute variceal bleeding (AVB) due to portal hypertension in cirrhotic patients. PATIENTS AND METHODS: This single-arm, prospective trial, conducted at two hospitals in Belgium and Egypt, included patients admitted to the emergency room with hematemesis and/or melena and known or suspected liver cirrhosis. All patients received urgent hemodynamic stabilization, octreotide (50 mcg bolus then 25 mcg/hour for 24 hours) and intravenous ceftriaxone (1 g/hour). Endoscopy to confirm AVB and Hemospray(r) application (if indicated) was performed within six hours of admission. Patients were kept under observation for 24 hours and underwent second endoscopy and definitive therapy (band ligation and/or cyanoacrylate injection in cases of gastric varices) the next day. RESULTS: Thirty-eight patients were admitted for suspected AVB, and 30 of these had confirmed AVB (70% male; mean age 59.5 years (range, 32.0-73 years)). Child-Pugh class C liver disease was present in 53.4%. Esophageal varices were observed in 83.4% of patients, gastric varices in 10%, and duodenal varices in 6.6%. Spurting bleeding at the time of endoscopy was observed in 43.4%. One patient developed hematemesis six hours after Hemospray(r) application and underwent emergency endoscopic band ligation. No major adverse events or mortalities were observed during 15-day follow-up. CONCLUSION: Hemospray(r) application was safe and effective at short-term follow-up for emergency treatment of AVB in cirrhotic patients. PMID- 26137305 TI - Scientific highlights at UEG Week 2015 in Barcelona. PMID- 26137304 TI - Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn's disease: Results from a randomised double-blind placebo-controlled study. AB - BACKGROUND: Vitamin D (vitD) supplementation may prolong remission in Crohn's disease (CD); however, the clinical efficacy and mechanisms are unclear. AIM: To determine changes in intestinal permeability (IP), antimicrobial peptide (AMP) concentrations and disease markers in CD, in response to vitD supplementation. METHODS: In a double-blind randomised placebo-controlled study, we assigned 27 CD patients in remission to 2000 IU/day vitD or placebo for 3 mos. We determined IP, plasma cathelicidin (LL-37 in ng/mL), human-beta-defensin-2 (hBD2 in pg/mL), disease activity (Crohn's Disease Activity Index (CDAI)), C-reactive protein (CRP in mg/L), fecal calprotectin (ug/g), Quality of Life (QoL) and serum 25 hydroxyvitamin D (25(OH)D in nmol/L) at 0 and 3 mos. RESULTS: At 3 mos., 25(OH)D concentrations were significantly higher in those whom were treated (p < 0.001). Intra-group analysis showed increased LL-37 concentrations (p = 0.050) and maintenance of IP measures in the treated group. In contrast, in the placebo group, the small bowel (p = 0.018) and gastro-duodenal permeability (p = 0.030) increased from baseline. At 3 mos., patients with 25(OH)D >= 75 nmol/L had significantly lower CRP (p = 0.019), higher QoL (p = 0.037), higher LL-37 concentrations (p < 0.001) and non-significantly lower CDAI scores (p = 0.082), compared to those with levels <75 nmol/L. CONCLUSION: Short-term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL-37 concentrations and maintenance of IP. Achieving 25(OH)D >= 75 nmol/l was accompanied by higher circulating LL-37, higher QoL scores and reduced CRP. Registered at ClinicalTrials.gov (NCT01792388). PMID- 26137306 TI - My experience with UEG classroom courses - a personal account from a participant. PMID- 26137307 TI - The ecological determinants of baboon troop movements at local and continental scales. AB - BACKGROUND: How an animal moves through its environment directly impacts its survival, reproduction, and thus biological fitness. A basic measure describing how an individual (or group) travels through its environment is Day Path Length (DPL), i.e., the distance travelled in a 24-hour period. Here, we investigate the ecological determinants of baboon (Papio spp.) troop DPL and movements at local and continental scales. RESULTS: At the continental scale we explore the ecological determinants of annual mean DPL for 47 baboon troops across 23 different populations, updating a classic study by Dunbar (Behav Ecol Sociobiol 31: 35-49, 1992). We find that variation in baboon DPLs is predicted by ecological dissimilarity across the genus range. Troops that experience higher average monthly rainfall and anthropogenic influences have significantly shorter DPL, whilst troops that live in areas with higher average annual temperatures have significantly longer DPL. We then explore DPLs and movement characteristics (the speed and distribution of turning angles) for yellow baboons (Papio cynocephalus) at a local scale, in the Issa Valley of western Tanzania. We show that our continental-scale model is a good predictor of DPL in Issa baboons, and that troops move significantly slower, and over shorter distances, on warmer days. We do not find any effect of season or the abundance of fruit resources on the movement characteristics or DPL of Issa baboons, but find that baboons moved less during periods of high fruit availability. CONCLUSION: Overall, this study emphasises the ability of baboons to adapt their ranging behaviour to a range of ecological conditions and highlights how investigations of movement patterns at different spatial scales can provide a more thorough understanding of the ecological determinants of movement. PMID- 26137308 TI - Outcome of mucormycosis after treatment: report of five cases. AB - Mucormycoses are serious infections caused by filamentous fungi of the order Mucorales. They occur most often in immunocompromised patients. We report five cases of mucormycosis in patients hospitalized in the Infectious Diseases Department in Sousse - Tunisia between 2000 and 2013. They were 4 males and one female, mean age 60 years. Three patients were diabetic and one patient had acute leukemia. The locations of mucormycosis were rhinocerebral, rhino-orbital, auricular, pulmonary and cutaneous. The Mucorales isolated were Rhizopus arrhizus in 3 cases and Lichteimia in 2 cases. All patients were treated with amphotericin B and 2 patients had, in addition, surgical debridement. Two patients died and 2 kept peripheral facial paralysis. PMID- 26137309 TI - First detection of insertion sequence element ISPa1328 in the oprD porin gene of an imipenem-resistant Pseudomonas aeruginosa isolate from an idiopathic pulmonary fibrosis patient in Marseille, France. AB - We report here the first case of a carbapenem-resistant Pseudomonas aeruginosa clinical isolate harboring the insertion sequence (IS) element ISPa1328 in the oprD gene in an idiopathic pulmonary fibrosis patient in France previously treated with imipenem. PMID- 26137310 TI - tcpC as a prospective new virulence marker in blood Escherichia coli isolates from sepsis patients admitted to the intensive care unit. AB - The prevalence of the tcpC in the blood Escherichia coli isolates collected from the sepsis patients admitted to the intensive care unit was investigated for the first time. The blood and faecal samples were collected from sepsis and nonsepsis patients, respectively. The prevalence of the tcpC and phylogroups was confirmed by gene-specific PCR. The occurrence of the tcpC in the blood E. coli isolates from sepsis patients was significantly higher than the faecal isolates. The higher prevalence of blood E. coli isolates among the pathogenic groups (B2, D) compared to the commensal groups (A, B1) suggests tcpC as a prospective new virulence marker for sepsis. PMID- 26137311 TI - Absence of Chlamydia-like organisms in pigs. AB - Porcine reproductive failure, especially abortion, causes significant economic loss in the pig industry. Waddlia chondrophila and Parachlamydia acanthamoebae are potential abortigenic agents for pigs. Therefore, we investigated the presence of these two Chlamydia-like organisms in abortion-related samples originating from Belgian pig farms. All investigated samples remained negative. PMID- 26137312 TI - Association between night work and cardiovascular diseases: analysis of the 3rd Korean working conditions survey. AB - OBJECTIVES: This study was conducted to investigate the relationship between night work and cardiovascular diseases among wage workers in Korea. METHODS: The study was based on the 3rd Korean Working Conditions Survey (KWCS; 2011). This study included 29,711 wage workers. We used the chi-squared test and logistic regression to examine the association between cardiovascular diseases and night work and cumulative night work. RESULTS: Among all of the paid workers, 12.5% reported doing night work >= 1 day per month. Night work was significantly associated with an increased risk of cardiovascular diseases (odds ratio [OR] 1.58, 95% confidence interval [CI] 1.11-2.25). Also, compared to the group that did not do night works, the group with higher cumulative night work demonstrated an increased risk for cardiovascular diseases (OR 1.81, 95% CI 1.19-2.74). CONCLUSIONS: This study suggests that night work is significantly associated with cardiovascular diseases. PMID- 26137313 TI - Minnesota multiphasic personality inventory as related factor for post traumatic stress disorder symptoms according to job stress level in experienced firefighters: 5-year study. AB - OBJECTIVES: As first responders to an increasing number of natural and manmade disasters, active-duty firefighters are at increased risk for physical and psychiatric impairment as reflected by high rates of posttraumatic stress disorder (PTSD). Because little is known about related factor with PTSD according to job stress level among firefighters, we assessed utility of the Minnesota Multiphasic Personality Inventory (MMPI) using 5-year medical surveillance. METHODS: Data were analyzed from 185 male firefighters without psychiatric disease history and who at assessments in 2006 and 2011 completed all questionnaires on personal behaviors (including exercise, drinking and smoking habits) and job history (including job duration and department). MMPI, Events Scale-Revised-Korean version (IES-R-K) and Korean Occupational Stress Scale-Short Form (KOSS-SF) were used to screen for personality trait, PTSD symptom presence and job stress level, respectively. IES-R-K subgroups were compared using two sample t- and chi2 tests, and factors influencing IES-R-K according to KOSS-SF were determined using uni- and multivariate logistic regression. RESULTS: Mean age and job duration were higher in PTSD-positive than negative groups. In multivariate analysis, increased PTSD risk was associated with: job duration (Odds ratio (OR) = 1.064, 95 % CI 1.012-1.118) for firefighters overall; masculinity-femininity (OR = 5.304, 95 % CI 1.191-23.624) and job duration (OR = 1.126, 95 % CI 1.003-1.265) for lower job stress level; and social introversion (OR = 3.727, 95 % CI 1.096-12.673) for higher job stress level. CONCLUSIONS: MMPI relates with PTSD according to job stress level among experienced firefighters. Masculinity-femininity and social introversion were the strongest related factor for PTSD symptom development in low and high job stress levels, respectively. PMID- 26137314 TI - Stent-graft treatment for extrahepatic portal vein hemorrhage after pancreaticoduodenectomy. AB - We report a case of intraperitoneal hemorrhage from the extrahepatic portal vein after pancreaticoduodenectomy for distal bile duct carcinoma. A stent-graft was deployed from the superior mesenteric vein to the main portal vein using a transhepatic approach. After the procedure, the patient remained free of intraperitoneal hemorrhage and was discharged 2 months later. PMID- 26137315 TI - Trends in Glaucoma Medication Expenditures under Universal Health Coverage: A National Population-Based Longitudinal Survey in Taiwan. AB - Medical care in Taiwan is well known for its low cost, high efficiency, high quality, excellent medical accessibility, and high equity. We investigate the trends in medication expenditures for glaucoma from 1997 to 2010. The results show that higher medical expenditures were incurred by patients who were aged >=40 years, male patients, and patients in the highest salary population whereas lower medical expenditures were incurred by blue-collar workers. The medications with the most significant increases in expenditure were prostaglandin analogs (PGAs), alpha-agonists, and fixed combinations, whereas the medications with the most significant decreases in expenditure were beta-blockers and cholinergic agonists. The number of trabeculectomies shows two downward break points in 1999 and 2000 when PGAs were listed and were reimbursed. These results suggest socioeconomic disparities in glaucoma care, as well as understanding of the changes in the expenditure of glaucoma medications under such universal health insurance coverage system. PMID- 26137316 TI - Histone Deacetylases Inhibitors in the Treatment of Retinal Degenerative Diseases: Overview and Perspectives. AB - Retinal degenerative diseases are one of the important refractory ophthalmic diseases, featured with apoptosis of photoreceptor cells. Histone acetylation and deacetylation can regulate chromosome assembly, gene transcription, and posttranslational modification, which are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. The histone deacetylase inhibitors (HDACis) have the ability to cause hyperacetylation of histone and nonhistone proteins, resulting in a variety of effects on cell proliferation, differentiation, anti-inflammation, and anti-apoptosis. Several HDACis have been approved for clinical trials to treat cancer. Studies have shown that HDACis have neuroprotective effects in nervous system damage. In this paper, we will summarize the neuroprotective effects of common HDACis in retinal degenerative diseases and make a prospect to the applications of HDACis in the treatment of retinal degenerative diseases in the future. PMID- 26137317 TI - ET-1 Plasma Levels, Aqueous Flare, and Choroidal Thickness in Patients with Retinitis Pigmentosa. AB - Purpose. To assess endothelin-1 (ET-1) plasma levels, choroidal thickness, and aqueous flare in patients with early stage retinitis pigmentosa (RP) and to search for possible correlations. Methods. We compared 24 RP patients with 24 healthy controls. Choroidal thickness and aqueous flare were measured, respectively, by using a spectral domain optical coherence tomography and a laser flare-cell meter, whereas plasma samples were obtained from each patient to evaluate ET-1 plasma levels. Results. Notably, RP subjects showed significantly increased ET-1 plasma levels and reduced choroidal thickness compared with controls: 2.143 +/- 0.258 versus 1.219 +/- 0.236 pg/mL, P < 0.002, and 226.75 +/- 76.37 versus 303.9 +/- 39.87 MUm, P < 0.03, respectively. Higher aqueous flare values were also demonstrated in RP compared to controls: in detail, 10.51 +/- 3.97 versus 5.66 +/- 1.29 photon counts/ms, P < 0.0001. Spearman's correlation test highlighted that the increase of ET-1 plasma levels was related with the decrease of choroidal thickness (r = -0.702; P < 0.023) and the increase of aqueous flare (r = 0.580; P < 0.007). Conclusions. Early stage RP patients show a breakdown of blood-ocular barrier and increased ET-1 plasma levels and these findings may contribute to the reduction of choroidal thickness. PMID- 26137318 TI - Prospective Randomized Study Comparing Combined Phaco-ExPress and Phacotrabeculectomy in Open Angle Glaucoma Treatment: 12-Month Follow-Up. AB - Purpose of the Study. To compare the efficacy and safety of phacotrabeculectomy (P-Trab) and phacoemulsification with the ExPress (P-ExPress) mini glaucoma shunt implantation. Study Plan. Prospective randomized study. Material and Methods. 85 eyes with cataract and unregulated open angle glaucoma. There were 46 eyes in the P-ExPress and 39 the P-Trab group. Intraocular pressure (IOP), the number of antiglaucoma medications, qualified and complete surgical success (defined as IOP <= 18.0 mmHg), visual acuity (CDVA), the number of endothelial cells, and postoperative complications and additional procedures were assessed. Results. After 12 months of observation, the average IOP in the P-Express group went from 26.4 +/- 9.3 down to 17.1 +/- 5 mmHg (P < 0.05) and from 27.9 +/- 12.9 down to 15.9 +/- 2.7 mmHg in the P-Trab group (P < 0.05). No significant differences in the amount of medications used after surgery and CDVA were discovered between the groups. In the P-ExPress group, greater loss of endothelial cells was noted (CDloss%), compared to the P-Trab group. Conclusions. Both P-ExPress and P-Trab have comparable efficacy and similar early postoperative complication profile. The presence of additional implant (as is the case of the ExPress mini glaucoma shunt implantation) may cause progressive loss of endothelial cells. PMID- 26137319 TI - Knocking Down Snrnp200 Initiates Demorphogenesis of Rod Photoreceptors in Zebrafish. AB - Purpose. The small nuclear ribonucleoprotein 200 kDa (SNRNP200) gene is a fundamental component for precursor message RNA (pre-mRNA) splicing and has been implicated in the etiology of autosomal dominant retinitis pigmentosa (adRP). This study aims to determine the consequences of knocking down Snrnp200 in zebrafish. Methods. Expression of the Snrnp200 transcript in zebrafish was determined via whole mount in situ hybridization. Morpholino oligonucleotide (MO) aiming to knock down the expression of Snrnp200 was injected into zebrafish embryos, followed by analyses of aberrant splicing and expression of the U4/U6-U5 tri-small nuclear ribonucleoproteins (snRNPs) components and retina-specific transcripts. Systemic changes and retinal phenotypes were further characterized by histological study and immunofluorescence staining. Results. Snrnp200 was ubiquitously expressed in zebrafish. Knocking down Snrnp200 in zebrafish triggered aberrant splicing of the cbln1 gene, upregulation of other U4/U6-U5 tri snRNP components, and downregulation of a panel of retina-specific transcripts. Systemic defects were found correlated with knockdown of Snrnp200 in zebrafish. Only demorphogenesis of rod photoreceptors was detected in the initial stage, mimicking the disease characteristics of RP. Conclusions. We conclude that knocking down Snrnp200 in zebrafish could alter regular splicing and expression of a panel of genes, which may eventually trigger rod defects. PMID- 26137320 TI - A Novel Device to Exploit the Smartphone Camera for Fundus Photography. AB - Purpose. To construct an inexpensive, convenient, and portable attachment for smartphones for the acquisition of still and live retinal images. Methods. A small optical device based on the principle of direct ophthalmoscopy was designed to be magnetically attached to a smartphone. Representative images of normal and pathological fundi were taken with the device. Results. A field-of-view up to ~20 degrees was captured at a clinical resolution for each fundus image. The cross polarization technique adopted in the optical design dramatically diminished corneal Purkinje reflections, making it possible to screen patients even through undilated pupils. Light emission proved to be well within safety limits. Conclusions. This optical attachment is a promising, inexpensive, and valuable alternative to the direct ophthalmoscope, potentially eliminating problems of poor exam skills and inexperienced observer bias. Its portability, together with the wireless connectivity of smartphones, presents a promising platform for screening and telemedicine in nonhospital settings. Translational Relevance. Smartphones have the potential to acquire retinal imaging for a portable ophthalmoscopy. PMID- 26137321 TI - Prevalence of Anemia and Associated Factors among Pregnant Women in North Western Zone of Tigray, Northern Ethiopia: A Cross-Sectional Study. AB - Background. Anemia affects the lives of more than 2 billion people globally, accounting for over 30% of the world's population. Anemia is a global public health problem occurring at all stages of the life cycle but the burden of the problem is higher in pregnant women particularly in developing countries. The aim of this study was to determine the prevalence of anemia and associated factors among pregnant women attending antenatal clinics in north western zone of Tigray, northern Ethiopia. Methods. A facility based cross-sectional study was employed. A systematic random sampling procedure was employed to select 714 pregnant women who were attending antenatal clinics in health facilities found in the study area from April to May 2014. The data was entered and analyzed using Epi-info version 3.5.1 and SPSS version 20.0 statistical software, respectively. Logistic regression analysis was used to identify factors associated with anemia among the study participants. All tests were two-sided and p value < 0.05 was considered statistically significant. Results. The overall prevalence of anemia (hemoglobin < 11 g/dL) among the pregnant women was 36.1% (95% CI = 32.7%-39.7%) of which 58.5% were mildly, 35.7% moderately, and 5.8% severely anemic. In pregnant women, rural residence (AOR = 1.75, 95% CI = 1.01-3.04), no education/being illiterate (AOR = 1.56, 95% CI = 1.03-2.37), absence of iron supplementation during pregnancy (AOR = 2.76, 95% CI = 1.92-5.37), and meal frequency of less than two times per day (AOR = 2.28, 95% CI = 1.06-4.91) were the independent predictors for increased anemia among the pregnant women. Conclusions. Anemia was found to be moderate public health problem in the study area. Residence, educational status, iron supplementation during pregnancy, and meal frequency per day were statistically associated with anemia among the pregnant women. Awareness creation and nutrition education on the importance of taking iron supplementation and nutritional counseling on consumption of extra meal and iron-rich foods during pregnancy are recommended to prevent anemia in the pregnant women. PMID- 26137322 TI - Continuous Positive Airway Pressure Device Time to Procurement in a Disadvantaged Population. AB - Introduction. The management of obstructive sleep apnea (OSA) in patients who cannot afford a continuous positive airway pressure (CPAP) device is challenging. In this study we compare time to CPAP procurement in three groups of patients diagnosed with OSA: uninsured subsidized by a humanitarian grant (Group 1), uninsured unsubsidized (Group 2), and those with Medicare or Medicaid (Group 3). We evaluate follow-up and adherence in Group 1. We hypothesize that additional factors, rather than just the ability to obtain CPAP, may uniquely affect follow up and adherence in uninsured patients. Methods. 30 patients were in Groups 1 and 2, respectively. 12 patients were in Group 3. Time of CPAP procurement from OSA diagnosis to CPAP initiation was assessed in all groups. CPAP adherence data was collected for Group 1 patients at 1, 3, 6, and 9 months. Results. There were no significant differences between groups in gender, age, body mass index, or apnea hypopnea index. The mean time to procurement in Group 1 was shorter compared to Group 2 but not significant. Compared to both Group 1 and Group 2, Group 3 patients had significantly shorter times to device procurement. Conclusion. Time to procurement of CPAP was significantly shorter in those with Medicaid/Medicare insurance compared to the uninsured. PMID- 26137323 TI - The Effect of Development in Respiratory Sensory Gating Measured by Electrocortical Activations. AB - The perception of respiratory sensations can be of significant importance to individuals for survival and greatly impact quality of life. Respiratory sensory gating, similar to somatosensory gating with exteroceptive stimuli, is indicative of brain cortices filtering out repetitive respiratory stimuli and has been investigated in adults with and without diseases. Respiratory gating can be tested with the respiratory-related evoked potential (RREP) method in the electroencephalogram with a paired inspiratory occlusion paradigm. Here, the RREP N1 component elicited by the second stimulus (S2) shows reduced amplitudes compared to the RREP N1 component elicited by the first stimulus (S1). However, little is known regarding the effect of development on respiratory sensory gating. The present study examined respiratory sensory gating in 22 typically developed school-aged children and 22 healthy adults. Paired inspiratory occlusions of 150-ms each with an inter-stimulus-interval of 500-ms were delivered randomly every 2-4 breaths during recording. The main results showed a significantly larger RREP N1 S2/S1 ratio in the children group than in the adult group. In addition, children compared to adults demonstrated significantly smaller N1 peak amplitudes in response to S1. Our results suggest that school aged children, compared to adults, display reduced respiratory sensory gating. PMID- 26137325 TI - Liver Trauma in the Kitchen: Preparing Whipped Cream with a Siphon Is Not without Risk. AB - We report the case of a 36-year-old woman suffering from liver injury caused by the malfunction of a whipped cream siphon. When this patient handled the whipped cream siphon, the screwed metallic upper part of the siphon was suddenly dissociated from its base and came violently striking her right hypochondrium. At first, the severity of injury was underestimated. Subsequently, due to the persistence of pain experienced by the patient, an abdominal CT scan was performed. It highlighted a severe liver injury with rupture of a branch of the hepatic artery. The evolution was favorable after completion of an embolization and a secondary capsular rupture. PMID- 26137324 TI - Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression. AB - Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine's antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine's antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n = 23, 0.79 +/- 0.15 mEq/L) or valproate (n = 13, 79.6 +/- 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure-the Montgomery-Asberg Depression Rating Scale (MADRS) was assessed before infusion and at numerous postinfusion time points. Both lithium (F 1,118 = 152.08, p < 0.001, and d = 2.27) and valproate (F 1,128 = 20.12, p < 0.001, and d = 0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F 1,28 = 2.51, p = 0.12, and d = 0.60). Serum lithium and valproate levels did not correlate with ketamine's antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithium may not potentiate ketamine's antidepressant efficacy in treatment-resistant bipolar depression. PMID- 26137326 TI - A Bullet Entered through the Open Mouth and Ended Up in the Parapharyngeal Space and Skull Base. AB - Shot from a revolver from a close range, a bullet pierced the chest of a policeman and entered through the open mouth of a young male person standing behind. The entry wound was found in the cheek mucosa adjacent to the left lower third molar. After hitting and fracturing the body and the ramus of the mandible, the bullet was deflected and was finally lodged in the parapharyngeal space and skull base, anterolateral to the transverse process of the atlas. The great vessels of the neck were not injured. The patient's condition was very critical but his life could be saved. The bullet was approached through a modified Blair's incision and was found to be lying over the carotid sheath. It was removed safely and the patient recovered completely. PMID- 26137327 TI - Thyroidectomy for Painful Thyroiditis Resistant to Steroid Treatment: Three New Cases with Review of the Literature. AB - Thyroidal pain is usually due to subacute thyroiditis (SAT). In more severe forms prednisone doses up to 40 mg daily for 2-3 weeks are recommended. Recurrences occur rarely and restoration of steroid treatment cures the disease. Rarely, patients with Hashimoto's thyroiditis (HT) have thyroidal pain (painful HT, PHT). Differently from SAT, occasional PHT patients showed no benefit from medical treatment so that thyroidectomy was necessary. We report three patients who did not show clinical response to prolonged high dose prednisone treatment: a 50-year old man, a 35-year-old woman, and a 33-year-old woman. Thyroidectomy was necessary, respectively, after nine-month treatment with 50 mg daily, two-month treatment with 75 mg daily, and one-month treatment with 50 mg daily. The two women were typical cases of PHT. Conversely, in the first patient, thyroid histology showed features of granulomatous thyroiditis, typical of SAT, without fibrosis or lymphocytic infiltration, typical of HT/PHT, coupled to undetectable serum anti-thyroid antibodies. Our data (1) suggest that not only PHT but also SAT may show resistance to steroid treatment and (2) confirm a previous observation in a single PHT patient that increasing prednisone doses above conventional maximal dosages may not be useful in these patients. PMID- 26137328 TI - A Case Report Demonstrating How the Clinical Presentation of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma Can Mimic Benign Riedel's Thyroiditis. AB - A 44-year-old female presented with a two-month history of a neck mass, sore throat, hoarseness, and intermittent dysphagia. Examination revealed a "woody" hard swelling arising from the right lobe of the thyroid. Clinically this was felt to be classical Riedel's thyroiditis (RT). Thyroid ultrasound showed a diffusely enlarged, low echogenicity thyroid with a multinodular goitre. An abnormal nodule extending across the isthmus was noted. Following a nondiagnostic fine needle aspiration, an open core biopsy was performed. This showed dense sclerotic fibrosis punctuated by nodular mononuclear inflammatory cells, which obscured follicular epithelial cells consistent with a fibrosing thyroiditis (Riedel's thyroiditis). A biopsy of pretracheal lymph nodes showed a sclerotic process throughout the lymph nodes and nests of epithelium bands with squamous differentiation obscured by a fibrous process. These findings raised the differential diagnosis of diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) with metastasis to lymph nodes. A total thyroidectomy and pretracheal lymph node dissection were performed. The final histological diagnosis was DSV-PTC. When managing a patient with presumed RT it is important to consider malignancy in the differential. DSV-PTC is one of the more aggressive forms of thyroid cancer but with early diagnosis and appropriate treatment patients may have excellent outcomes. PMID- 26137329 TI - Large Bowel Obstruction Due to a Big Gallstone Successfully Treated with Endoscopic Mechanical Lithotripsy. AB - Colonic gallstone ileus in an uncommon mechanical bowel obstruction caused by intraluminal impaction of one or more gallstones. The surgical management of gallstone ileus is complex and is potentially of high risk. There have been reports of gallstone extractions using various endoscopic modalities to relieve the obstruction. In this report we present the technique employed to successfully perform a mechanical lithotripsy and extraction of a large gallstone embedded in a sigmoid colon affected by diverticular stenosis. We passed through the stenosis with a 11.3 mm videoscope with 3.7 mm channel. A large lithotripsy extraction basket was used to catch and break up the stone and fragments were removed using the same basket. The patient was discharged asymptomatic three days after the procedure. Using appropriate devices mechanical lithotripsy is a safe and effective method to treat colonic obstruction and avoid surgery in the setting of gallstone ileus even in case of big stones. PMID- 26137331 TI - Aromatase Inhibitor-Induced Erythrocytosis in a Patient Undergoing Hormonal Treatment for Breast Cancer. AB - Aromatase inhibitors (AIs) are most commonly used for breast cancer patients with hormone receptor positive disease. Although the side effect profile of aromatase inhibitors is well known, including common side effects like arthralgia, bone pain, arthritis, hot flashes, and more serious problems like osteoporosis, we present a case of an uncommon side effect of these medications. We report the case of a postmenopausal woman on adjuvant hormonal therapy with anastrozole after completing definitive therapy for stage IIIB estrogen receptor-positive breast cancer, who was referred to hematology service for evaluation of persistent erythrocytosis. Primary and known secondary causes of polycythemia were ruled out. On further evaluation, we found that her erythrocytosis began after initiation of anastrozole and resolved after it was discontinued. We discuss the pathophysiology of aromatase inhibitor-induced erythrocytosis and reference of similar cases reported in the literature. PMID- 26137330 TI - Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18. AB - Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician. Both cases came to our attention because a fetal anatomy scan at 20 weeks of gestation revealed multiple anomalies. Karyotyping of cultured amniocytes showed nonmosaic trisomies 13 and 18, respectively. Cytogenetic investigation of cytotrophoblast cells from multiple placental biopsies showed a low proportion of nontrisomic cells in each case, but this was considered too small for explaining the false negative NIPT result. The discordant results also could not be explained by early gestational age, elevated maternal weight, a vanishing twin, or suboptimal storage or transport of samples. The root cause of the discrepancies could, therefore, not be identified. The couples involved experienced difficulties in accepting the unexpected and late-adverse outcome of their pregnancy. We recommend that all parties involved in caring for couples who choose NIPT should collaborate to clarify false negative results in order to unravel possible biological causes and to improve the process of patient care from initial counseling to communication of the result. PMID- 26137332 TI - Is It a Pathogenic ATP7A Variation and Is It Menkes Disease? PMID- 26137333 TI - Bilateral Maternal Pelvic Kidneys Presenting as a Tumor Previa: Sonographic Diagnosis and Obstetric Management. AB - Renal ectopia occurs when the kidney fails to ascend normally to the retroperitoneal renal fossa. Bilateral cases have also been reported but are very rare. Pregnancy and labor with maternal renal ectopia provides a unique challenge to the obstetricians attempting to prevent damage to the kidneys during labor and allow safe delivery. We describe a case of congenital bilateral pelvic kidneys assessed and diagnosed by 3D sonography as "tumor previa" and managed accordingly. PMID- 26137334 TI - A Case of Chronic Abdominal Neuropathic Pain and Burning after Female Genital Cutting. AB - Introduction. Female genital cutting is prevalent in the Middle Eastern and African countries. This ritual entails not only immediate complications such as infection, pain, and haemorrhage, but also chronic ones including dysmenorrhea and dyspareunia. However, there is limited data on neuropathic pain secondary to female genital mutilation when searching the literature. Case. This case discusses a 38-year-old female with a history of infibulation who presented with a chronic burning abdominal and anterior vulvar pain including the related investigations and treatment. Discussion. This case brings to light the additional delayed complication of this ritual: sensory neuropathy. Our goal is to educate health professionals to be aware of these complications and to appropriately investigate and treat them in order to find a solution to relieve the patients' symptoms. PMID- 26137335 TI - Embryonal Carcinoma in Cryptorchid Abdominal Testis of an Infant. AB - Cryptorchidism is a known predisposing factor for the development of testicular tumors in adults. Age of patient at the time of treatment of undescended testes has some bearing on the risk of neoplasia. Testicular neoplasia at the time of primary surgery for cryptorchidism has been reported rarely in prepubertal period. We report a case where embryonal carcinoma was detected in a cryptorchid testis of an infant. PMID- 26137336 TI - Meniscal Bearing Dislocation of Unicompartmental Knee Arthroplasty with Faint Symptom. AB - We experienced two cases of atypical lateral dislocations of meniscal bearing in UKA (unicompartmental knee arthroplasty) without manifest symptoms. The dislocated bearing, which jumped onto the wall of tibial components, was found on radiographs in periodic medical examination although they could walk. Two thicker size bearing exchanges were promptly performed before metallosis and loosening of components. Continual examination is important to mobile bearing type of UKA because slight or less symptoms may disclose such unique dislocation. One case showed malrotation of the femoral component on 3D image. Anteroposterior view hardly disclosed the malrotation of the femoral component. Epicondylar view is an indispensable view of importance, and it can demonstrate the rotation of the femoral component. The the femoral distal end is wedge shaped and is wider posteriorly. If the femoral component is set according to the shape of medial condyle, the femoral component shifts to medial site compared with tibial component in flexion. It can account for such rare dislocation as follows. If excessive force applies on most medial side of the bearing during flexion, the lateral part of the bearing pops and the force squeezes it laterally simultaneously. Finally, the bearing jumps onto the lateral wall of the tibial component. PMID- 26137337 TI - A Challenging Case of Multifocal Mycobacterium marinum Osteoarticular Infection in a Patient with Anorexia Nervosa. AB - Disseminated infection due to Mycobacterium marinum is rare but has been described in immunosuppressed and transplant recipients. We describe a case of multifocal osteoarticular involvement by this pathogen in a patient with anorexia nervosa. Serial surgical debridements and a prolonged course of antimicrobial therapy including intravenous amikacin, imipenem, and oral ethambutol and azithromycin were needed to treat the infection. Cell mediated immune deficits related to the patient's anorexia nervosa predisposed her to a severe infection with M. marinum. Aggressive surgical intervention in conjunction with multiple antimicrobial agents helped cure the infection. PMID- 26137338 TI - Primary Small Cell Carcinoma of the Hypopharynx: A Case Report of a Rare Tumor. AB - Introduction. Primary hypopharynx involvement of small cell carcinoma is very rare and very few cases have been reported in the literature. Here, we report a case of primary small cell carcinoma of the hypopharynx in a male patient. Case Report. A 50-year-old man presented with a 6-month history of sore throat and swellings in the right side of the neck. Direct laryngoscopy and biopsy revealed small cell carcinoma of the hypopharynx located in the right pyriform sinus. Discussion. Small cell carcinoma of the hypopharynx has no clear treatment modality due to the rarity of the disease. Systemic chemotherapy and radiotherapy should have priority among the therapy regimens because of the high metastatic potential of the tumor. PMID- 26137339 TI - Extramedullary Plasmacytoma of the Larynx Treated by a Surgical Endoscopic Approach and Radiotherapy. AB - Extramedullary plasmacytoma (EMP) is a rare variant of plasma cell myeloma that affects soft tissues. The head and neck region are the most affected sites, although others have also been described. Herein we report an uncommon case of EMP of the larynx in a 65-year-old male who presented with a history of progressive dysphonia and hoarseness. Laryngeal fiberscopy evidenced a reddish pedicled voluminous mass in the left false cords and ventricle. Microscopic suspension laryngoscopy was performed under general anaesthesia and a 4 W Acublade CO2 Laser was used for transoral resection of the lesion. This was followed by adjuvant radiotherapy, with the widely recommended doses on the supraglottic region, to achieve better local control. Diagnosis of EMP is based on immunohistochemistry and the exclusion of systemic plasma cell proliferative disorders. Diagnosis of solitary EMP can be made only if studies for disseminated disease and X-ray and/or magnetic resonance imaging of the spine, pelvis, femurs, and humerus and bone marrow biopsy are negative. As there are no internationally established guidelines, treatment of EMP is mainly based on consensus of expert opinion. PMID- 26137340 TI - 45,X/47,XXX Mosaicism and Short Stature. AB - We describe the case of a ten-year-old girl with short stature and 45,X/47,XXX genotype. She also suffered from vesicoureteric reflux and kidney dysfunction prior to having surgery on her ureters. Otherwise, she does not have any of the characteristics of Turner nor Triple X syndrome. It has been shown that this mosaic condition as well as other varieties creates a milder phenotype than typical Turner syndrome, which is what we mostly see in our patient. However, this patient is a special case, because she is exceptionally short. Overall, one cannot predict the resultant phenotype in these mosaic conditions. This creates difficulty in counseling parents whose children or fetuses have these karyotypes. PMID- 26137341 TI - Interstitial Lung Disease of the UIP Variant as the Only Presenting Symptom of Rheumatoid Arthritis. AB - Rheumatoid arthritis is a chronic inflammatory disease primarily manifesting with symptoms of joint pain. It also involves multiple organ systems in the body, including the lungs. Interstitial lung disease (ILD) is the most common form of pulmonary involvement in rheumatoid arthritis (RA). Without the typical symptoms such as chronic joint pain, establishing the diagnosis of RA could be quite challenging and a high index of suspicion is thereby required to diagnose ILD in patients with RA, thereby delaying treatment and increasing morbidity and mortality. We report a case of a 67-year-old Hispanic male with no previous history of rheumatoid arthritis or symptoms of typical joint pain who comes to the hospital only with the chief complaints of progressive worsening of shortness of breath for a duration of 6 months and was eventually diagnosed with ILD of the usual interstitial pneumonia variant with serologies positive for rheumatoid arthritis. PMID- 26137342 TI - Primary Amyloidosis Manifesting as Cholestatic Jaundice after Laparoscopic Cholecystectomy. AB - A 71-year-old female patient with cholelithiasis who had undergone laparoscopic cholecystectomy was admitted with obstructive jaundice (total bilirubin ~6 mg/dL) three months later. An ERCP was performed, in which a gallstone was found, followed by a sphincterotomy and cleansing of the bile duct. Due to deterioration of jaundice (>25 mg/dL), a new, unsuccessful ERCP and stent placement was carried out. Because of ongoing cardiac failure, she underwent an echocardiogram which revealed restrictive cardiomyopathy possibly due to amyloidosis. A liver biopsy was performed, which was positive for amyloid deposits in the liver, and the diagnosis was confirmed by the detection of monoclonal lambda IgG protein in urine. The patient's jaundice gradually deteriorated and she died one week later from hepatic insufficiency. PMID- 26137343 TI - Dropped Gallstones Causing a Perihepatic Abscess and Empyema. AB - Iatrogenic perforation of the gallbladder during laparoscopic cholecystectomy is a well-known occurrence; however, the consequences of spillage of gallstones in the peritoneum and particularly intrathoracic complications are less defined. We describe the delayed development of a perihepatic abscess and empyema in a patient five years following laparoscopic cholecystectomy secondary to dropped gallstones. A 53-year-old man with medical history significant for a laparoscopic cholecystectomy five years prior to acute cholecystitis presented with purulent cough, hemoptysis, night sweats, and right-upper quadrant (RUQ) pain. Computed tomography (CT) scan revealed 5.4 cm right-sided subpulmonic and 5.9 cm perihepatic fluid collections with an 8 mm focal radiopaque density within the perihepatic fluid collection. Open intra-abdominal exploration resulted in retrieval of a 1 cm intraperitoneal gallstone. Laparoscopic cholecystectomy is a common surgical operation during which gallstone spillage can occur, causing both intra-abdominal and intrathoracic complications, presenting even years after surgery. This necessitates an attempt to retrieve all free intra-abdominal gallstones during the initial operation. PMID- 26137344 TI - Complete Expulsion of Testicular Prosthesis via the Scrotum: A Case-Based Review of the Preventive Surgical Strategies. AB - Testicular prostheses are regularly used in urological surgery and are important for postoperative psychological well-being in many patients undergoing orchiectomy. One of the recognised complications of this procedure is graft extrusion, which can result in significant morbidity for patients and require operative reintervention. Whilst most cases of extrusion involve upward graft migration to the external inguinal ring or direct displacement through the scrotal skin, we present an unusual case of complete expulsion of testicular implant three weeks postoperatively through a previously healthy scrotum. During surgical insertion of testicular prostheses, the urological surgeon must carefully consider the different surgical strategies at each step of the operation to prevent future extrusion of the graft. A stepwise review of the preventive surgical strategies to reduce the risk of graft extrusion encompasses the choice of optimal surgical incision, the technique of dissection to create the receiving anatomical pouch, the method of fixation of the implant within the receiving hemiscrotum, and the adoption of good postoperative care measures in line with the principles of sound scrotal surgery. PMID- 26137345 TI - Influences on Decision Making Identified by Parents of Children Receiving Pediatric Palliative Care. AB - BACKGROUND: Parental decision making is a critical component in the provision of palliative and end-of-life care, yet factors that parents perceive as influencing this process, when they are making decisions for their children, have not been well characterized. METHODS: As part of a mixed-methods cohort study, we interviewed 73 parents of 50 pediatric patients who were referred to the hospital's pediatric palliative care service. The semistructured interviews focused on "decision making for your child"; the interviews were recorded and transcribed. A random sample (n = 13) was first coded and analyzed for core themes, and these themes were then cross-validated with a second random sample (n = 3) of interviews. RESULTS: Four dominant interrelated themes permeated parents' discussions about the decisions they were making for their children and the process of decision making. First, Orientation and Direction (including the subthemes of Goals and Hopes, Spirituality and Meaning, and Purposeful Effort) connotes the parents' effort to establish and clarify the broad context of decision making. Second, Defining What Is Good for the Child (including the subthemes of Quality of Life and Suffering, and Normalcy and Normalization) conveys how the parents posed questions and pondered what decisions would be in the child's best interests. Third, the entwined theme of Relationships, Communication, and Support reflects how parents reported the social and interactive nature of decision making. Fourth, the theme of Feelings and Personal Accountability focuses inward as parents report efforts to deal with their emotional responses and self-judgments. CONCLUSIONS: Parents report grappling with several influences upon their decision-making processes that extend well beyond the standard discussions of medical information exchanges and the evaluation of risks and benefits. Decision support for these parents should account for these diverse influences. PMID- 26137347 TI - The Role of Pharmacogenetic Testing in the Amelioration of Antidepressant-Related Motor Disturbances in 2 Young Adult Men With Major Depressive Disorder. AB - This report describes the cases of 2 young adult men with depressive symptoms who experienced severe and disruptive motor disturbances while taking serotonin reuptake inhibitors. Both patients had a long history of medication failures and complex presentations. Genetic testing was utilized to guide effective treatment plans and to provide insight into previous medication failures. Most notably, testing in these patients revealed variations in the serotonin transporter protein and cytochrome P450 2D6 and 2C19 enzymes. These cases demonstrate the utility of genetic testing in clinical practice to help identify effective treatment plans in psychiatric patients. PMID- 26137346 TI - Psychogenic Purpura (Gardner-Diamond Syndrome). AB - Psychogenic purpura, also known as Gardner-Diamond syndrome or autoerythrocyte sensitization syndrome, is a rare condition characterized by spontaneous development of painful edematous skin lesions progressing to ecchymosis over the next 24 hours. Severe stress and emotional trauma always precede the skin lesions. The condition is most commonly seen in women, but isolated cases have been reported in adolescents and in males. Psychodermatologic evaluation and dermatology and psychiatry liaison have been successful in the treatment of these patients. This report provides an overview of psychogenic purpura and presents the case of a 15-year-old girl. PMID- 26137348 TI - Collaboration and Referral Between Internal Medicine and Psychiatry. PMID- 26137349 TI - Factitious Disorder Manifesting as Hematemesis and Hematochezia. PMID- 26137350 TI - Nabilone for the Treatment of Dementia-Associated Sexual Disinhibition. PMID- 26137351 TI - Prevention of Sudden Death in Patients With Epilepsy. PMID- 26137352 TI - New Onset of Compulsive Gambling Associated With Modafinil: A Case Report. PMID- 26137353 TI - Escalating Ingestion of Razor Blades in a Patient With Borderline Personality Disorder. PMID- 26137354 TI - Evaluation of Changes in Citalopram Prescribing Patterns Following a US Food and Drug Administration Alert: A Retrospective Cohort Study. AB - OBJECTIVE: The US Food and Drug Administration (FDA) issued a warning stating that patients older than 60 years are not recommended to receive doses of citalopram exceeding 20 mg daily due to concerns of corrected QT (QTc) prolongation. The purpose of this study is to assess the impact of the FDA warning on prescribing patterns of citalopram in patients 60 years of age and older. METHOD: This is a retrospective cohort study of hospitalized patients 60 years of age and older prescribed citalopram from October 24, 2010, to August 24, 2011 and from November 24, 2011, to September 24, 2012. Records were examined for the presence of baseline risk factors for QTc prolongation and torsades de pointes. RESULTS: The issuance of an FDA warning was not associated with an observable change in prescribing patterns of citalopram. A total of 98.8% of patients had at least 1 risk factor for QTc prolongation. No significant difference in the total number of risk factors was seen between groups (P = .915). No differences were seen in risk factors prewarning and postwarning, except a higher percentage had left ventricular hypertrophy (P = .001) or history of syncope (P = .043) prior to the warning. More subjects were prescribed concomitant proarrhythmic medications (P = .009) after the FDA warning was issued. Similar percentages of each group were receiving daily dosages > 20 mg of citalopram (P = .600). CONCLUSIONS: The issuance of an FDA warning did not produce observable changes in prescribing patterns of citalopram. Modifiable risk factors and optimal dosing may be targets of interventions aimed at promoting safer use of citalopram. PMID- 26137355 TI - An Analysis of Relapse Rates and Predictors of Relapse in 2 Randomized, Placebo Controlled Trials of Desvenlafaxine for Major Depressive Disorder. AB - OBJECTIVE: To evaluate relapse rates and predictors of relapse in 2 randomized, placebo-controlled trials of desvenlafaxine for major depressive disorder (MDD). METHOD: Study 1: week 8 responders to open-label desvenlafaxine 50 mg/d entered a 12-week open-label stability phase. Patients with a continuing, stable response at week 20 were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 50 mg/d or placebo). Study 1 was conducted between June 2009 and March 2011 at 87 sites worldwide. Study 2: week 12 responders to open-label desvenlafaxine 200 or 400 mg/d were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 200 mg/d, 400 mg/d, or placebo). Study 2 was conducted between June 2003 and August 2005 at 49 sites in Europe, the United States, and Taiwan. Relapse was assessed separately by study with log-rank test using protocol definitions of relapse and with 17-item Hamilton Depression Rating Scale (HDRS-17) score >= 16 at any time during the double-blind phase. Kaplan-Meier estimates evaluated time to relapse, censoring data at months 1, 2, and 3 and overall; treatments were compared using hazard ratios. Cox proportional hazards models assessed relapse predictors. RESULTS: Overall relapse rates for all definitions were significantly lower for desvenlafaxine versus placebo for both studies (all P <= .002). In study 1, rates were significantly lower for desvenlafaxine versus placebo at month 2 (P = .016) and month 3 (P = .007) using the protocol definition. In study 2, relapse rates were significantly lower for desvenlafaxine versus placebo at months 1, 2, and 3 for both definitions (P < .0001-.002). Hazard ratios were similar at months 1, 2, and 3 and overall for both studies (0.382-0.639). CONCLUSIONS: Desvenlafaxine 50 to 400 mg/d effectively prevented relapse at 6 months. Desvenlafaxine significantly prevented relapse early (month 1) versus placebo only in study 2. TRIAL REGISTRATION: ClinicalTrials.gov identifiers:NCT00887224 and NCT00075257. PMID- 26137356 TI - Psychological Intervention in Primary Care After Earthquakes in Lorca, Spain. AB - OBJECTIVE: After the earthquakes that occurred in Lorca, Spain, on May 11, 2011, the regional mental health management employed 2 clinical psychologists for 6 months to provide care to people referred by primary care physicians. The objective was to address the expected increased demand for treatment of mental disorders, notably posttraumatic stress disorder (PTSD) and adjustment disorders. METHOD: Referred individuals were evaluated and treated according to a clinical protocol designed ad hoc from June 12, 2011, to November 30, 2011. The protocol provided a stepped intervention guided by clinical and psychometric assessment using "normalization" for those with no psychiatric diagnosis, brief group treatment for mild to moderate PTSD or adjustment disorders, individual treatment for more severe PTSD, and referral to the local mental health center for other mental health disorders. Standard adult and child scales to assess posttraumatic, depression, and anxiety symptoms and resilience were used at initial assessment to guide treatment allocation and repeated to assess outcome status. Psychologists also provided a clinical assessment of symptom resolution at the end of the study. RESULTS: Rates of symptom resolution and improvements on all scales (PTSD, depression, anxiety, and resilience) demonstrated clinically and statistically significant improvement in all treatment groups (P = .000). Dropout was low. Medications were prescribed frequently to adults; no child received medication as a result of the earthquakes. No case of mental disorder related to the earthquakes was referred to the local mental health center during the 6 months of psychologist intervention. CONCLUSION: The structured intervention resulted in a high resolution of cases and low dropout, allowing treatment of a larger number of people with optimal frequency (weekly), devoting more time to the most severe cases and less to those moderately or mildly affected. PMID- 26137357 TI - Genetic and Clinical Factors Affecting Plasma Clozapine Concentration. AB - OBJECTIVE: To assess (1) the variance of plasma clozapine levels; (2) the relative importance of sex, smoking habits, weight, age, and specific genetic variants of cytochrome P450 1A2 (CYP1A2), uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), and multidrug resistance protein 1 (MDR1) on plasma levels of clozapine; and (3) the relation between plasma clozapine levels, fasting glucose levels, and waist circumference. METHOD: There were 113 patients on clozapine treatment recruited from psychosis outpatient clinics in Stockholm County, Sweden. Patients had genotype testing for single nucleotide polymorphisms: 2 in MDR1, 3 in CYP1A2, and 1 in UGT1A4. Multiple and logistic regression were used to analyze the relations. RESULTS: There was a wide variation in plasma concentrations of clozapine (mean = 1,615 nmol/L, SD = 1,354 nmol/L), with 37% of the samples within therapeutic range (1,100-2,100 nmol/L). Smokers had significantly lower plasma clozapine concentrations than nonsmokers (P <= .03). There was a significant association between the rs762551 A allele of CYP1A2 and lower plasma clozapine concentration (P <= .05). Increased fasting glucose level was 3.7-fold more frequent in CC and CA genotypes than AA genotype (odds ratio = 0.27; 95% confidence interval, 0.10-0.72). There was no significant relation between higher fasting glucose levels, larger waist circumference, and higher clozapine levels. CONCLUSIONS: It is difficult to predict plasma clozapine concentration, even when known individual and genetic factors are considered. Therefore, therapeutic drug monitoring is recommended in patients who are treated with clozapine. PMID- 26137358 TI - Incidence and Timing of Taper/Posttherapy-Emergent Adverse Events Following Discontinuation of Desvenlafaxine 50 mg/d in Patients With Major Depressive Disorder. AB - OBJECTIVE: The purpose of this post hoc analysis was to evaluate the incidence and timing of taper/posttherapy-emergent adverse events (TPAEs) following discontinuation of long-term treatment with desvenlafaxine (administered as desvenlafaxine succinate). METHOD: This was a phase 4, randomized, double-blind, placebo-controlled study conducted at 38 research centers within the United States between March 2010 and February 2011. Adult outpatients with major depressive disorder (MDD; DSM-IV-TR criteria) who completed 24 weeks of open label treatment with desvenlafaxine 50 mg/d were randomly assigned to 1 of 3 groups for the double-blind taper phase: desvenlafaxine 50 mg/d for 4 weeks (no discontinuation), desvenlafaxine 25 mg/d for 1 week followed by placebo for 3 weeks (taper), or placebo for 4 weeks (abrupt discontinuation). The primary endpoint, Discontinuation-Emergent Signs and Symptoms Scale (DESS) score over the first 2 weeks of the taper phase, was described previously. Secondary assessments included incidence and timing of TPAEs (any adverse event that started or increased in severity during the double-blind phase) and the percentage of patients who could not continue the taper phase due to discontinuation symptoms. The Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) assessed MDD status. RESULTS: A total of 480 patients enrolled in the open-label phase; the full analysis set included 357 patients (taper, n = 139; abrupt discontinuation, n = 146; no discontinuation, n = 72). TPAEs occurred in all groups through week 4. The incidence of any TPAE was lower for taper versus abrupt discontinuation at week 1 (P < .001), similar at week 2, and lower for taper versus abrupt discontinuation at weeks 3 and 4 (P <= .034). The most common TPAEs (incidence >= 3%) in the taper group were nausea and headache (3% each) at week 1 and dizziness (5%) and headache (4%) at week 2. The most common TPAEs in the abrupt discontinuation group were dizziness (8%), headache (8%), nausea (4%), irritability (3%), and diarrhea (3%) at week 1 and headache (3%) at weeks 2 and 3. The most common TPAE in the no discontinuation group was nausea (6%) at week 2. CONCLUSION: The overall incidence of any TPAE was lower in the taper versus abrupt discontinuation groups. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01056289. PMID- 26137359 TI - Effective Research Strategies for Trainees in Internal Medicine Residency Programs. AB - For most training programs, the development of research endeavors among trainees is an ongoing challenge. In this article, we review various considerations when attempting to undertake research activities within an internal medicine residency training program, including availability of institutional resources (eg, dedicated research time for trainees and faculty, available faculty mentors, accessible adjunctive personnel), engagement of residents into research, classic project quagmires in training programs, the institutional review board, publication options (eg, letters to the editor, case reports, literature reviews, original research reports), and journal submission strategies. Given that research entails multiple components and distinct skills, the overall program goal should be to make research an educationally understandable process for trainees. Research can be a rewarding activity when nurtured in a facilitating educational environment. PMID- 26137360 TI - Depression and Anxiety Following Early Pregnancy Loss: Recommendations for Primary Care Providers. AB - Early pregnancy loss is a shocking and traumatic event for women and their families. Miscarriage usually induces an intense period of emotional distress. This reaction tends to improve over the following several months, but some residual psychological concerns remain. It is important to screen for depression and anxiety in patients following a miscarriage. Most women in this circumstance do become pregnant again, yet mood disturbances can still coexist. When women are having difficulties at conception, worries may be magnified. Most women and physicians see post-miscarriage intervention as desired, and it is important to provide appropriate treatment. Management of depressive and anxiety symptoms after pregnancy loss can benefit future patient well-being. PMID- 26137361 TI - Moving Forward. PMID- 26137362 TI - Calming the Agitated Demented Patient. PMID- 26137363 TI - Ultra-widefield retinal MHz-OCT imaging with up to 100 degrees viewing angle. AB - We evaluate strategies to maximize the field of view (FOV) of in vivo retinal OCT imaging of human eyes. Three imaging modes are tested: Single volume imaging with 85 degrees FOV as well as with 100 degrees and stitching of five 60 degrees images to a 100 degrees mosaic (measured from the nodal point). We employ a MHz OCT system based on a 1060nm Fourier domain mode locked (FDML) laser with a depth scan rate of 1.68MHz. The high speed is essential for dense isotropic sampling of the large areas. Challenges caused by the wide FOV are discussed and solutions to most issues are presented. Detailed information on the design and characterization of our sample arm optics is given. We investigate the origin of an angle dependent signal fall-off which we observe towards larger imaging angles. It is present in our 85 degrees and 100 degrees single volume images, but not in the mosaic. Our results suggest that 100 degrees FOV OCT is possible with current swept source OCT technology. PMID- 26137364 TI - Intravital fluorescence imaging of mouse brain using implantable semiconductor devices and epi-illumination of biological tissue. AB - The application of the fluorescence imaging method to living animals, together with the use of genetically engineered animals and synthesized photo-responsive compounds, is a powerful method for investigating brain functions. Here, we report a fluorescence imaging method for the brain surface and deep brain tissue that uses compact and mass-producible semiconductor imaging devices based on complementary metal-oxide semiconductor (CMOS) technology. An image sensor chip was designed to be inserted into brain tissue, and its size was 1500 * 450 MUm. Sample illumination is also a key issue for intravital fluorescence imaging. Hence, for the uniform illumination of the imaging area, we propose a new method involving the epi-illumination of living biological tissues, and we performed investigations using optical simulations and experimental evaluation. PMID- 26137365 TI - DistancePPG: Robust non-contact vital signs monitoring using a camera. AB - Vital signs such as pulse rate and breathing rate are currently measured using contact probes. But, non-contact methods for measuring vital signs are desirable both in hospital settings (e.g. in NICU) and for ubiquitous in-situ health tracking (e.g. on mobile phone and computers with webcams). Recently, camera based non-contact vital sign monitoring have been shown to be feasible. However, camera-based vital sign monitoring is challenging for people with darker skin tone, under low lighting conditions, and/or during movement of an individual in front of the camera. In this paper, we propose distancePPG, a new camera-based vital sign estimation algorithm which addresses these challenges. DistancePPG proposes a new method of combining skin-color change signals from different tracked regions of the face using a weighted average, where the weights depend on the blood perfusion and incident light intensity in the region, to improve the signal-to-noise ratio (SNR) of camera-based estimate. One of our key contributions is a new automatic method for determining the weights based only on the video recording of the subject. The gains in SNR of camera-based PPG estimated using distancePPG translate into reduction of the error in vital sign estimation, and thus expand the scope of camera-based vital sign monitoring to potentially challenging scenarios. Further, a dataset will be released, comprising of synchronized video recordings of face and pulse oximeter based ground truth recordings from the earlobe for people with different skin tones, under different lighting conditions and for various motion scenarios. PMID- 26137366 TI - Blind source separation of ex-vivo aorta tissue multispectral images. AB - Blind Source Separation methods (BSS) aim for the decomposition of a given signal in its main components or source signals. Those techniques have been widely used in the literature for the analysis of biomedical images, in order to extract the main components of an organ or tissue under study. The analysis of skin images for the extraction of melanin and hemoglobin is an example of the use of BSS. This paper presents a proof of concept of the use of source separation of ex-vivo aorta tissue multispectral Images. The images are acquired with an interference filter-based imaging system. The images are processed by means of two algorithms: Independent Components analysis and Non-negative Matrix Factorization. In both cases, it is possible to obtain maps that quantify the concentration of the main chromophores present in aortic tissue. Also, the algorithms allow for spectral absorbance of the main tissue components. Those spectral signatures were compared against the theoretical ones by using correlation coefficients. Those coefficients report values close to 0.9, which is a good estimator of the method's performance. Also, correlation coefficients lead to the identification of the concentration maps according to the evaluated chromophore. The results suggest that Multi/hyper-spectral systems together with image processing techniques is a potential tool for the analysis of cardiovascular tissue. PMID- 26137367 TI - Blood flow velocity vector field reconstruction from dual-beam bidirectional Doppler OCT measurements in retinal veins. AB - In this paper, we demonstrate the possibility to reconstruct the actual blood flow velocity vector field in retinal microvessels from dual-beam bidirectional Doppler optical coherence tomography measurements. First, for a better understanding of measured phase patterns, several flow situations were simulated on the basis of the known dual beam measurement geometry. We were able to extract the vector field parameters that determine the measured phase pattern, allowing for the development of an algorithm to reconstruct the velocity vector field from measured phase data. In a next step, measurements were performed at a straight vessel section and at a venous convergence; the obtained phase data were evaluated by means of the new approach. For the straight vessel section, the reconstructed flow velocity vector field yielded a parabolic flow. For the venous convergence, however, the reconstructed vector field deviated from a parabolic profile, but was in very good accordance with the simulated vector field for the given vessel geometry. The proposed algorithm allows predictions of the velocity vector field. Moreover, the algorithm is also sensitive to directional changes of the flow velocity as small as <1 degrees , thereby offering insight in the flow characteristics of the non-Newtonian fluid blood in microvessels. PMID- 26137368 TI - Impact of vessel diameter and bandwidth of illumination in sidestream dark-field oximetry. AB - We investigate the possibility of oxygen saturation estimation from images obtained by the sidestream dark-field (SDF) technique. The SDF technique is a method for microvascular imaging. In SDF imaging, light enters a tissue directly from illumination sources configured around a camera and then the camera captures the light scattered by the tissue. To advance the capability of the SDF imaging system, we develop a SDF oximetry method with LED illumination sources. In this paper, we evaluate some SDF oximetry methods from virtual SDF images obtained by the Monte Carlo photon propagation simulation. As a result, we verify that SDF imaging allows the estimation of oxygen saturation of the individual vessels from virtual images using the average extinction coefficients considering the bandwidth of the illumination and the effect of the integration of the camera. PMID- 26137370 TI - Improved sparse reconstruction for fluorescence molecular tomography with L1/2 regularization. AB - Fluorescence molecular tomography (FMT) is a promising imaging technique that allows in vivo visualization of molecular-level events associated with disease progression and treatment response. Accurate and efficient 3D reconstruction algorithms will facilitate the wide-use of FMT in preclinical research. Here, we utilize L1/2-norm regularization for improving FMT reconstruction. To efficiently solve the nonconvex L1/2-norm penalized problem, we transform it into a weighted L1-norm minimization problem and employ a homotopy-based iterative reweighting algorithm to recover small fluorescent targets. Both simulations on heterogeneous mouse model and in vivo experiments demonstrated that the proposed L1/2-norm method outperformed the comparative L1-norm reconstruction methods in terms of location accuracy, spatial resolution and quantitation of fluorescent yield. Furthermore, simulation analysis showed the robustness of the proposed method, under different levels of measurement noise and number of excitation sources. PMID- 26137369 TI - Impact of motion-associated noise on intrinsic optical signal imaging in humans with optical coherence tomography. AB - A growing body of evidence suggests that phototransduction can be studied in the human eye in vivo by imaging of fast intrinsic optical signals (IOS). There is consensus concerning the limiting influence of motion-associated imaging noise on the reproducibility of IOS-measurements, especially in those employing spectral domain optical coherence tomography (SD-OCT). However, no study to date has conducted a comprehensive analysis of this noise in the context of IOS-imaging. In this study, we discuss biophysical correlates of IOS, and we address motion associated imaging noise by providing correctional post-processing methods. In order to avoid cross-talk of adjacent IOS of opposite signal polarity, cellular resolution and stability of imaging to the level of individual cones is likely needed. The optical Stiles-Crawford effect can be a source of significant IOS imaging noise if alignment with the peak of the Stiles-Crawford function cannot be maintained. Therefore, complete head stabilization by implementation of a bite bar may be critical to maintain a constant pupil entry position of the OCT beam. Due to depth-dependent sensitivity fall-off, heartbeat and breathing associated axial movements can cause tissue reflectivity to vary by 29% over time, although known methods can be implemented to null these effects. Substantial variations in reflectivity can be caused by variable illumination due to changes in the beam pupil entry position and angle, which can be reduced by an adaptive algorithm based on slope-fitting of optical attenuation in the choriocapillary lamina. PMID- 26137372 TI - Laser induced fluorescence spectroscopy of various carbon nanostructures (GO, G and nanodiamond) in Rd6G solution. AB - The effect of carbon nanostructures such as graphene (G), graphene oxide (GO) and nanodiamond (ND) on the spectral properties of Rhodamine 6G (Rd6G) emission due to the laser induced fluorescence (LIF) was investigated. It is shown that the addition of carbon nano- structures lead to sensible Red/Blue shifts which depend on the optical properties and surface functionality of nanoparticles. The current theories such as resonance energy transfer (RET), fluorescence quenching and photon propagation in scattering media support the experimental findings. Stern Volmer curves for dynamic and static quenching of Rd6G molecules embedded with G, GO and nanodiamond are correlated with spectral shifts. Furthermore, time evolution of the spectral shift contributes to determine loading/release rates of fluorescent species with large S-parameter on the given nano-carriers. PMID- 26137371 TI - Dual-modality fiber-based OCT-TPL imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques. AB - New optical imaging techniques that provide contrast to study both the anatomy and composition of atherosclerotic plaques can be utilized to better understand the formation, progression and clinical complications of human coronary artery disease. We present a dual-modality fiber-based optical imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques that combines optical coherence tomography (OCT) and two-photon luminescence (TPL) imaging. Experimental results from ex vivo human coronary arteries show that OCT and TPL optical contrast in recorded OCT-TPL images is complimentary and in agreement with histological analysis. Molecular composition (e.g., lipid and oxidized-LDL) detected by TPL imaging can be overlaid onto plaque microstructure depicted by OCT, providing new opportunities for atherosclerotic plaque identification and characterization. PMID- 26137373 TI - Non-invasive measurement of choroidal volume change and ocular rigidity through automated segmentation of high-speed OCT imaging. AB - We have developed a novel optical approach to determine pulsatile ocular volume changes using automated segmentation of the choroid, which, together with Dynamic Contour Tonometry (DCT) measurements of intraocular pressure (IOP), allows estimation of the ocular rigidity (OR) coefficient. Spectral Domain Optical Coherence Tomography (OCT) videos were acquired with Enhanced Depth Imaging (EDI) at 7Hz during ~50 seconds at the fundus. A novel segmentation algorithm based on graph search with an edge-probability weighting scheme was developed to measure choroidal thickness (CT) at each frame. Global ocular volume fluctuations were derived from frame-to-frame CT variations using an approximate eye model. Immediately after imaging, IOP and ocular pulse amplitude (OPA) were measured using DCT. OR was calculated from these peak pressure and volume changes. Our automated segmentation algorithm provides the first non-invasive method for determining ocular volume change due to pulsatile choroidal filling, and the estimation of the OR constant. Future applications of this method offer an important avenue to understanding the biomechanical basis of ocular pathophysiology. PMID- 26137374 TI - In vivo photothermal optical coherence tomography for non-invasive imaging of endogenous absorption agents. AB - In vivo photothermal optical coherence tomography (OCT) is demonstrated for cross sectional imaging of endogenous absorption agents. In order to compromise the sensitivity, imaging speed, and sample motion immunity, a new photothermal detection scheme and phase processing method are developed. Phase-resolved swept source OCT and fiber-pigtailed laser diode (providing excitation at 406 nm) are combined to construct a high-sensitivity photothermal OCT system. OCT probe and excitation beam coaxially illuminate and are focused on tissues. The photothermal excitation and detection procedure is designed to obtain high efficiency of photothermal effect measurement. The principle and method of depth-resolved cross sectional imaging of absorption agents with photothermal OCT has been derived. The phase-resolved thermal expansion detection algorithm without motion artifact enables in vivo detection of photothermal effect. Phantom imaging with a blood phantom and in vivo human skin imaging are conducted. A phantom with guinea-pig blood as absorber has been scanned by the photothermal OCT system to prove the concept of cross-sectional absorption agent imaging. An in vivo human skin measurement is also performed with endogenous absorption agents. PMID- 26137375 TI - Hybrid algorithm for simulating the collimated transmittance of homogeneous stratified turbid media. AB - In this work we describe the development of a program that simulates the propagation of photons through refractive and reflecting optical components such as lenses, mirrors and stops that includes a biological tissue sample as the main issue to be investigated in order to get a simulated value of light distribution, in particular, of the unscattered light. The analysis of the photons that travel through the sample is based on the program Monte Carlo Multi-Layered with some modifications that consider a Gaussian beam as initial source of light. Position, directional cosines and weight of photons exiting the turbid media are used to propagate them through an optical system. As a mean of validation of the program, we selected a typical optical system for measurement of collimated transmittance. Therefore, several tests were carried out to find the optical system that gives the theoretical collimated transmittance at different values of the optical properties of the turbid media. Along this validation, the optimal experimental configuration is found. Using this results, a comparison between the simulated optimal configuration and the experimental set-up was done, by using a colloidal suspension as a turbid media. PMID- 26137376 TI - Assessment of imaging with extended depth-of-field by means of the light sword lens in terms of visual acuity scale. AB - We present outcomes of an imaging experiment using the refractive light sword lens (LSL) as a contact lens in an optical system that serves as a simplified model of the presbyopic eye. The results show that the LSL produces significant improvements in visual acuity of the simplified presbyopic eye model over a wide range of defocus. Therefore, this element can be an interesting alternative for the multifocal contact and intraocular lenses currently used in ophthalmology. The second part of the article discusses possible modifications of the LSL profile in order to render it more suitable for fabrication and ophthalmological applications. PMID- 26137377 TI - Towards next-generation time-domain diffuse optics for extreme depth penetration and sensitivity. AB - Light is a powerful tool to non-invasively probe highly scattering media for clinical applications ranging from oncology to neurology, but also for molecular imaging, and quality assessment of food, wood and pharmaceuticals. Here we show that, for a paradigmatic case of diffuse optical imaging, ideal yet realistic time-domain systems yield more than 2-fold higher depth penetration and many decades higher contrast as compared to ideal continuous-wave systems, by adopting a dense source-detector distribution with picosecond time-gating. Towards this aim, we demonstrate the first building block made of a source-detector pair directly embedded into the probe based on a pulsed Vertical-Cavity Surface Emitting Laser (VCSEL) to allow parallelization for dense coverage, a Silicon Photomultiplier (SiPM) to maximize light harvesting, and a Single-Photon Avalanche Diode (SPAD) to demonstrate the time-gating capability on the basic SiPM element. This paves the way to a dramatic advancement in terms of increased performances, new high impact applications, and availability of devices with orders of magnitude reduction in size and cost for widespread use, including quantitative wearable imaging. PMID- 26137378 TI - Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging. AB - The dosimetry of light-based therapies critically depends on both optical and vascular parameters. We utilized spatial frequency domain imaging to quantify optical and vascular parameters, as well as estimated light penetration depth from 17 nonmelanoma skin cancer patients. Our data indicates that there exist substantial spatial variations in these parameters. Characterization of these parameters may inform understanding and optimization of the clinical response of light-based therapies. PMID- 26137379 TI - Molecular imaging needles: dual-modality optical coherence tomography and fluorescence imaging of labeled antibodies deep in tissue. AB - Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue. PMID- 26137380 TI - Ultra-thin and flexible endoscopy probe for optical coherence tomography based on stepwise transitional core fiber. AB - We present an ultra-thin fiber-body endoscopy probe for optical coherence tomography (OCT) which is based on a stepwise transitional core (STC) fiber. In a minimalistic design, our probe was made of spliced specialty fibers that could be directly used for beam probing optics without using a lens. In our probe, the OCT light delivered through a single-mode fiber was efficiently expanded to a large mode field of 24 MUm diameter for a low beam divergence. The size of our probe was 85 MUm in the probe's diameter while operated in a 160-MUm thick protective tubing. Through theoretical and experimental analyses, our probe was found to exhibit various attractive features in terms of compactness, flexibility and reliability along with its excellent fabrication simplicity. PMID- 26137381 TI - Dual-slit confocal light sheet microscopy for in vivo whole-brain imaging of zebrafish. AB - In vivo functional imaging at single-neuron resolution is an important approach to visualize biological processes in neuroscience. Light sheet microscopy (LSM) is a cutting edge in vivo imaging technique that provides micron-scale spatial resolution at high frame rate. Due to the scattering and absorption of tissue, however, conventional LSM is inadequate to resolve cells because of the attenuated signal to noise ratio (SNR). Using dual-beam illumination and confocal dual-slit detection, here a dual-slit confocal LSM is demonstrated to obtain the SNR enhanced images with frame rate twice as high as line confocal LSM method. Through theoretical calculations and experiments, the correlation between the slit's width and SNR was determined to optimize the image quality. In vivo whole brain structural imaging stacks and the functional imaging sequences of single slice were obtained for analysis of calcium activities at single-cell resolution. A two-fold increase in imaging speed of conventional confocal LSM makes it possible to capture the sequence of the neurons' activities and help reveal the potential functional connections in the whole zebrafish's brain. PMID- 26137382 TI - Localization of cortical tissue optical changes during seizure activity in vivo with optical coherence tomography. AB - Optical coherence tomography (OCT) is a high resolution, minimally invasive imaging technique, which can produce depth-resolved cross-sectional images. In this study, OCT was used to detect changes in the optical properties of cortical tissue in vivo in mice during the induction of global (pentylenetetrazol) and focal (4-aminopyridine) seizures. Through the use of a confidence interval statistical method on depth-resolved volumes of attenuation coefficient, we demonstrated localization of regions exhibiting both significant positive and negative changes in attenuation coefficient, as well as differentiating between global and focal seizure propagation. PMID- 26137383 TI - Quantitative single-mode fiber based PS-OCT with single input polarization state using Mueller matrix. AB - We present a simple but effective method to quantitatively measure the birefringence of tissue by an all single-mode fiber (SMF) based polarization sensitive optical coherence tomography (PS-OCT) with single input polarization state. We theoretically verify that our SMF based PS-OCT system can quantify the phase retardance and optic axis orientation after a simple calibration process using a quarter wave plate (QWP). Based on the proposed method, the quantification of the phase retardance and optic axis orientation of a Berek polarization compensator and biological tissues were demonstrated. PMID- 26137384 TI - Decrease in fluorescence lifetime by glycation of collagen and its application in determining advanced glycation end-products in human dentin. AB - Advanced Glycation End-products (AGEs) are produced by the Maillard reaction, which causes cross-linking of collagen and results in changes in the mechanical properties of collagen tissues. Several types of AGE fluoresce, and measurement of this fluorescence is effective for determining the presence of AGEs. Because fluorescence intensity by steady-state fluorometry is affected by sample surface condition and light source, we focused on fluorescence lifetime measurement (FLM). We found that fluorescence lifetime of collagen gel decreased with glycation progress. In vivo application of FLM for determination of AGEs was confirmed in human dentin. PMID- 26137385 TI - Deep, high contrast microscopic cell imaging using three-photon luminescence of beta-(NaYF4:Er(3+)/NaYF4) nanoprobe excited by 1480-nm CW laser of only 1.5-mW. AB - It is challenging to achieve deep microscopic imaging for the strong scattering in biotissue. An efficient three-photon luminescence can effectively increase the penetration depth. Here we report that beta-NaYF4: Er(3+)/NaYF4 UCNPs were excited by a 1480-nm CW-laser and emitted 543/653-nm light through a three-photon process. With the merit of the hexagonal crystal phase, sub-milliwatt laser power was utilized to excite the UCNP-probed cells to minimize the heating effect. The polymer-coated UCNPs were shown to be harmless to cells. The deep, high contrast in vitro microscopic imaging was implemented through an artificial phantom. Imaging depth of 800 MUm was achieved using only 1.5 mW excitation and a 0.7 NA objective. The green/red emission intensities ratio after penetrating the phantom was studied, indicating that longer emission wavelength is preferred for deep multiphoton microscopy. The proposed and demonstrated beta-UCNPs would have great potential in three-photon microscopy. PMID- 26137386 TI - Rapid imaging of large tissues using high-resolution stage-scanning microscopy. AB - Rapid and high-resolution imaging of large tissues is essential in biological research, like brain neuron connectivity research and cancer margins imaging. Here a novel stage-scanning confocal microscopy was developed for rapid imaging of large tissues. Line scanning methods and strip imaging strategy were used to increase the imaging speed. The scientific CMOS was used as line detector in sub array mode and the optical sectioning ability can be easily adjusted by changing the number of line detectors according to different samples. Fluorescent beads imaging showed resolutions of 0.47 MUm, 0.56 MUm, and 1.56 MUm in the X, Y, and Z directions, respectively, with a 40 * objective lens. A 10 * 10 mm(2) coronal plane with enough signal intensity could be imaged in about 88 sec at a sampling resolution of 0.16 MUm/pixel. Rapid imaging of mouse brain slices demonstrated the applicability of this system in visualizing neuronal details at high frame rate. PMID- 26137387 TI - Fibre-coupled multiphoton microscope with adaptive motion compensation. AB - To address the challenge of sample motion during in vivo imaging, we present a fibre-coupled multiphoton microscope with active axial motion compensation. The position of the sample surface is measured using optical coherence tomography and fed back to a piezo actuator that adjusts the axial location of the objective to compensate for sample motion. We characterise the system's performance and demonstrate that it can compensate for axial sample velocities up to 700 um/s. Finally we illustrate the impact of motion compensation when imaging multiphoton excited autofluorescence in ex vivo mouse skin. PMID- 26137388 TI - Femtosecond lasing from a fluorescent protein in a one dimensional random cavity. AB - We present evidence of random lasing from the fluorescent protein DsRed2 embedded in a random one-dimensional cavity. Lasing is achieved when a purified protein solution, placed inside a layered random medium, is optically excited with a femtosecond pump pulse in the direction perpendicular to the plane of random layers. We demonstrate that pumping with ultrashort pulses resulted in a lasing threshold two orders of magnitude lower than that found for nanosecond excitation. PMID- 26137389 TI - Nonlinear optical microscopy of early stage (ICRS Grade-I) osteoarthritic human cartilage. AB - In a synovial joint, the articular cartilage is directly affected during the progression of Osteoarthritis (OA). The characterization of early stage modification in extra-cellular matrix of cartilage is essential for detection as well as understanding the progression of disease. The objective of this study is to demonstrate the potential and capability of nonlinear optical microscopy for the morphological investigation of early stage osteoarthritic cartilage. ICRS Grade-I cartilage sections were obtained from the femoral condyle of the human knee. The surface of articular cartilage was imaged by second harmonic generation and two-photon excited fluorescence microscopy. Novel morphological features like microsplits and wrinkles were observed, which would otherwise not be visible in other clinical imaging modalities (e.g., CT, MRI, ultrasound and arthroscope. The presence of superficial layer with distinct collagen fibrils parallel to the articular surface in 4 specimens out of 14 specimens, indicates that different phases of OA within ICRS Grade-I can be detected by SHG microscopy. All together, the observed novel morphologies in early stage osteoarthritic cartilage indicates that SHG microscopy might be a significant tool for the assessment of cartilage disorder. PMID- 26137390 TI - Feasibility of level-set analysis of enface OCT retinal images in diabetic retinopathy. AB - Pathology segmentation in retinal images of patients with diabetic retinopathy is important to help better understand disease processes. We propose an automated level-set method with Fourier descriptor-based shape priors. A cost function measures the difference between the current and expected output. We applied our method to enface images generated for seven retinal layers and determined correspondence of pathologies between retinal layers. We compared our method to a distance-regularized level set method and show the advantages of using well defined shape priors. Results obtained allow us to observe pathologies across multiple layers and to obtain metrics that measure the co-localization of pathologies in different layers. PMID- 26137391 TI - Feature space optical coherence tomography based micro-angiography. AB - Current optical coherence tomography (OCT) based micro-angiography is prone to noise that arises from static background. This work presents a novel feature space based optical micro-angiography (OMAG) method (fsOMAG) that can effectively differentiate flow signal from static background in the feature space. fsOMAG consists of two steps. In the first step a classification map is generated that provides criterion for classification in the second step to extract functional blood flow from experimental data set. The performance of fsOMAG is examined through phantom experiments and in-vivo human retinal imaging, and compared with the existing OMAG. The results indicate its potential for clinical applications. PMID- 26137392 TI - High-performance sub-terahertz transmission imaging system for food inspection. AB - Unlike X-ray systems, a terahertz imaging system can distinguish low-density materials in a food matrix. For applying this technique to food inspection, imaging resolution and acquisition speed ought to be simultaneously enhanced. Therefore, we have developed the first continuous-wave sub-terahertz transmission imaging system with a polygonal mirror. Using an f-theta lens and a polygonal mirror, beam scanning is performed over a range of 150 mm. For obtaining transmission images, the line-beam is incorporated with sample translation. The imaging system demonstrates that a pattern with 2.83 mm line-width at 210 GHz can be identified with a scanning speed of 80 mm/s. PMID- 26137393 TI - Accurate real-time depth control for CP-SSOCT distal sensor based handheld microsurgery tools. AB - This paper presents a novel intuitive targeting and tracking scheme that utilizes a common-path swept source optical coherence tomography (CP-SSOCT) distal sensor integrated handheld microsurgical tool. To achieve micron-order precision control, a reliable and accurate OCT distal sensing method is required; simultaneously, a prediction algorithm is necessary to compensate for the system delay associated with the computational, mechanical and electronic latencies. Due to the multi-layered structure of retina, it is necessary to develop effective surface detection methods rather than simple peak detection. To achieve this, a shifted cross-correlation method is applied for surface detection in order to increase robustness and accuracy in distal sensing. A predictor based on Kalman filter was implemented for more precise motion compensation. The performance was first evaluated using an established dry phantom consisting of stacked cellophane tape. This was followed by evaluation in an ex-vivo bovine retina model to assess system accuracy and precision. The results demonstrate highly accurate depth targeting with less than 5 MUm RMSE depth locking. PMID- 26137394 TI - Applying Resilience Promotion Training Among Special Forces Police Officers. AB - Police Special Forces (a.k.a. special weapons and tactics [SWAT]) officers are tasked with responding to the most critical situations, including incidents that require specialized skills and equipment beyond typical policing activities. In this study, we tested the feasibility of applying Arnetz and colleagues' resilience promotion training that was developed for patrol officers to SWAT team officers (n = 18). The resilience promotion training program included psychoeducation focused on police stress and resilience, and the practice of resilience promotion techniques (controlled breathing and imagery) while listening to audio-recorded critical incident scenarios. The aims of this study were to (a) examine if a resilience training program was relevant and accepted by SWAT team officers and (b) assess participants' physiological stress responses (heart rate, respiration) during the resilience training sessions to note if there were improvements in stress responding over time. Our findings revealed that participants were able to significantly reduce their average heart rate and improve their ability to engage in controlled respiration (i.e., breathing) during simulated critical incidents over the course of the 5-day training. Improvements in stress responding were observed even when the critical incident scenarios became more graphic. Results suggest that an intervention to reduce stress responses of SWAT officers to critical incident scenarios works in a simulated training setting. Translation of these findings to real-world occupational hazards is a recommended next step. PMID- 26137395 TI - CD4+ T cells potently induce epithelial-mesenchymal-transition in premalignant and malignant pancreatic ductal epithelial cells-novel implications of CD4+ T cells in pancreatic cancer development. AB - Chronic pancreatitis (CP) is a risk factor of pancreatic ductal adenocarcinoma (PDAC) and characterized by a pronounced desmoplastic reaction with CD4+ T cells accounting for the majority of the stromal T cell infiltrate. Epithelial mesenchymal-transition (EMT) is a critical process for metastasis by which epithelial/carcinoma cells become enabled to disseminate probably prior to tumor formation. To investigate whether CD4+ T cells induce EMT in human pancreatic ductal epithelial cells, premalignant H6c7 cells were mono- or co-cultured with human CD4+CD25+CD127-CD49d- regulatory T cells (T-regs) or CD4+CD25- T-effector cells (T-effs) being isolated by negative magnetic bead separation from blood of healthy donors. Particularly in the presence of activated T-effs, H6c7 cells acquired a spindle-shaped morphology, reduced E-cadherin expression, and elevated expression of the mesenchymal proteins vimentin, L1CAM, and ZEB-1. This was accompanied by an increased invasive behavior. Moreover, activated T-effs exerted similar effects in the PDAC cell line T3M4. Blocking of TNF-alpha and IL-6 being released at greater amounts into supernatants during co-cultures with activated T effs attenuated the EMT-associated alterations in H6c7 cells. Supporting these findings, EMT-associated alterations (exemplified by reduced E-cadherin expression and enhanced expression of vimentin and L1CAM) were predominantly detected in ductal epithelium of CP tissues surrounded by a dense stroma enriched with CD4+ T cells. Overall this study points to a novel role of CD4+ T cells beyond their immune function in pancreatic tumorigenesis and underscores the view that EMT induction in pancreatic ductal epithelial cells represents an early event in PDAC development being essentially promoted by inflammatory processes. PMID- 26137396 TI - NG2 proteoglycan-dependent recruitment of tumor macrophages promotes pericyte endothelial cell interactions required for brain tumor vascularization. AB - Early stage growth of intracranial B16F10 tumors is reduced by 87% in myeloid specific NG2 null (Mac-NG2ko) mice and by 77% in pericyte-specific NG2 null (PC NG2ko) mice, demonstrating the importance of the NG2 proteoglycan in each of these stromal compartments. In both genotypes, loss of pericyte-endothelial cell interaction results in numerous structural defects in tumor blood vessels, including decreased formation of endothelial cell junctions and decreased assembly of the vascular basal lamina. All vascular deficits are larger in Mac NG2ko mice than in PC-NG2ko mice, correlating with the greater decrease in pericyte-endothelial cell interaction in Mac-NG2ko animals. Accordingly, tumor vessels in Mac-NG2ko mice have a smaller diameter, lower degree of patency, and higher degree of leakiness than tumor vessels in PC-NG2ko mice, leading to less efficient tumor blood flow and to increased intratumoral hypoxia. While reduced pericyte interaction with endothelial cells in PC-NG2ko mice is caused by loss of NG2-dependent pericyte activation of beta1 integrin signaling in endothelial cells, reduced pericyte-endothelial cell interaction in Mac-NG2ko mice is due to a 90% reduction in NG2-dependent macrophage recruitment to tumors. The absence of a macrophage-derived signal(s) in Mac-NG2ko mice results in the loss of pericyte ability to associate with endothelial cells, possibly due to reduced expression of N-cadherin by both pericytes and endothelial cells. PMID- 26137397 TI - Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial. AB - VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells. PMID- 26137398 TI - B7-H6-mediated downregulation of NKp30 in NK cells contributes to ovarian carcinoma immune escape. AB - In this study the phenotype and function of tumor-associated NK cells from peritoneal fluids of a selected cohort of patients with seropapillary ovarian carcinoma were analyzed. In > 50% of these patients, the expression of the activating receptor NKp30 in tumor-associated NK cells was substantially reduced as compared to autologous peripheral blood (PB) NK cells. The impaired expression of this receptor was associated with the presence of one of its cellular ligands (B7-H6), which was detectable as a surface/cytosolic molecule in tumor cells and as a soluble molecule in the peritoneal fluid. NK cells from patients expressing this NKp30low phenotype displayed an impaired interferon-gamma (IFNgamma) production and cytolytic function when tested against target cells expressing surface B7-H6. Our data also suggest that in these patients, the defective expression and function of NKp30 may be induced by the chronic engagement of this receptor by soluble B7-H6 or by tumor cells expressing this ligand. The impairment of NK cell functions described herein could represent a novel mechanism by which the tumor microenvironment may contribute to the escape from immune surveillance. PMID- 26137399 TI - Diversity index of mucosal resident T lymphocyte repertoire predicts clinical prognosis in gastric cancer. AB - A characteristic immunopathology of human cancers is the induction of tumor antigen-specific T lymphocyte responses within solid tumor tissues. Current strategies for immune monitoring focus on the quantification of the density and differentiation status of tumor-infiltrating T lymphocytes; however, properties of the TCR repertoire - including antigen specificity, clonality, as well as its prognostic significance - remain elusive. In this study, we enrolled 28 gastric cancer patients and collected tumor tissues, adjacent normal mucosal tissues, and peripheral blood samples to study the landscape and compartmentalization of these patients' TCR beta repertoire by deep sequencing analyses. Our results illustrated antigen-driven expansion within the tumor compartment and the contracted size of shared clonotypes in mucosa and peripheral blood. Most importantly, the diversity of mucosal T lymphocytes could independently predict prognosis, which strongly underscores critical roles of resident mucosal T-cells in executing post-surgery immunosurveillance against tumor relapse. PMID- 26137400 TI - Mast cell/MDSC a liaison immunosuppressive for tumor microenvironment. AB - The instauration of an immunosuppressive microenvironment is a key event in cancer development and progression. Here, we discuss increasing evidences of the crosstalk between myeloid-derived suppressor cells (MDSCs) and mast cells (MCs) as a new fuel for the cancer immunosuppressive machinery. PMID- 26137401 TI - Modulating gut immunity and neoplasia with oral cytokine adjuvants. AB - Oral administration of particulate IL-10 suppressed polyposis, ameliorated systemic pathology and extended lifespan in APCmin/+ mice. Therapeutic effect was associated with selective activity of IL-10 on intestinal CD4+Foxp3+RORgammat+IL 17+ pathogenic T-regulatory cells. Studies were recently extended to a bacterially-driven murine colon adenocarcinoma model with similar results. Clinical implications of these findings are discussed. PMID- 26137402 TI - Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8+ T-cell responses and immune memory. AB - Cancer chemotherapy using cytotoxic drugs can induce immunogenic tumor cell death; however, dosing regimens and schedules that enable single-agent chemotherapy to induce adaptive immune-dependent ablation of large, established tumors with activation of long-term immune memory have not been identified. Here, we investigate this issue in a syngeneic, implanted GL261 glioma model in immune competent mice given cyclophosphamide on a 6-day repeating metronomic schedule. Two cycles of metronomic cyclophosphamide treatment induced sustained upregulation of tumor-associated CD8+ cytotoxic T lymphocyte (CTL) cells, natural killer (NK) cells, macrophages, and other immune cells. Expression of CTL- and NK cell-shared effectors peaked on Day 6, and then declined by Day 9 after the second cyclophosphamide injection and correlated inversely with the expression of the regulatory T cell (Treg) marker Foxp3. Sustained tumor regression leading to tumor ablation was achieved after several cyclophosphamide treatment cycles. Tumor ablation required CD8+ T cells, as shown by immunodepletion studies, and was associated with immunity to re-challenge with GL261 glioma cells, but not B16 F10 melanoma or Lewis lung carcinoma cells. Rejection of GL261 tumor re-challenge was associated with elevated CTLs in blood and increased CTL infiltration in tumors, consistent with the induction of long-term, specific CD8+ T-cell anti GL261 tumor memory. Co-depletion of CD8+ T cells and NK cells did not inhibit tumor regression beyond CD8+ T-cell depletion alone, suggesting that the metronomic cyclophosphamide-activated NK cells function via CD8a+ T cells. Taken together, these findings provide proof-of-concept that single-agent chemotherapy delivered on an optimized metronomic schedule can eradicate large, established tumors and induce long-term immune memory. PMID- 26137403 TI - Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications. AB - Immunomodulatory monoclonal antibodies (mAbs) differ from their tumor-targeting counterparts because they exert therapeutic effects by directly interacting with soluble or (most often) cellular components of the immune system. Besides holding promise for the treatment of autoimmune and inflammatory disorders, immunomodulatory mAbs have recently been shown to constitute a potent therapeutic weapon against neoplastic conditions. One class of immunomodulatory mAbs operates by inhibiting safeguard systems that are frequently harnessed by cancer cells to establish immunological tolerance, the so-called "immune checkpoints." No less than 3 checkpoint-blocking mAbs have been approved worldwide for use in oncological indications, 2 of which during the past 12 months. These molecules not only mediate single-agent clinical activity in patients affected by specific neoplasms, but also significantly boost the efficacy of several anticancer chemo , radio- or immunotherapies. Here, we summarize recent advances in the development of checkpoint-blocking mAbs, as well as of immunomodulatory mAbs with distinct mechanisms of action. PMID- 26137404 TI - Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy. AB - The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers. PMID- 26137406 TI - Human derived dimerization tag enhances tumor killing potency of a T-cell engaging bispecific antibody. AB - Bispecific antibodies (BsAbs) have proven highly efficient T cell recruiters for cancer immunotherapy by virtue of one tumor antigen-reactive single chain variable fragment (scFv) and another that binds CD3. In order to enhance the antitumor potency of these tandem scFv BsAbs (tsc-BsAbs), we exploited the dimerization domain of the human transcription factor HNF1alpha to enhance the avidity of a tsc-BsAb to the tumor antigen disialoganglioside GD2 while maintaining functional monovalency to CD3 to limit potential toxicity. The dimeric tsc-BsAb showed increased avidity to GD2, enhanced T cell mediated killing of neuroblastoma and melanoma cell lines in vitro (32-37 fold), exhibited a near 4-fold improvement in serum half-life, and enhanced tumor ablation in mouse xenograft models. We propose that the use of this HNF1alpha-derived dimerization tag may be a novel and effective strategy to increase the potency of T-cell engaging antibodies for clinical cancer immunotherapy. PMID- 26137407 TI - GITR agonist enhances vaccination responses in lung cancer. AB - An immune tolerant tumor microenvironment promotes immune evasion of lung cancer. Agents that antagonize immune tolerance will thus aid the fight against this devastating disease. Members of the tumor necrosis factor receptor (TNFR) family modulate the magnitude, duration and phenotype of immune responsiveness to antigens. Among these, GITR expressed on immune cells functions as a key regulator in inflammatory and immune responses. Here, we evaluate the GITR agonistic antibody (DTA-1) as a mono-therapy and in combination with therapeutic vaccination in murine lung cancer models. We found that DTA-1 treatment of tumor bearing mice increased: (i) the frequency and activation of intratumoral natural killer (NK) cells and T lymphocytes, (ii) the antigen presenting cell (APC) activity in the tumor, and (iii) systemic T-cell specific tumor cell cytolysis. DTA-1 treatment enhanced tumor cell apoptosis as quantified by cleaved caspase-3 staining in the tumors. DTA-1 treatment increased expression of IFNgamma, TNFalpha and IL-12 but reduced IL-10 levels in tumors. Furthermore, increased anti-angiogenic chemokines corresponding with decreased pro-angiogenic chemokine levels correlated with reduced expression of the endothelial cell marker Meca 32 in the tumors of DTA-1 treated mice. In accordance, there was reduced tumor growth (8-fold by weight) in the DTA-1 treatment group. NK cell depletion markedly inhibited the antitumor response elicited by DTA-1. DTA-1 combined with therapeutic vaccination caused tumor rejection in 38% of mice and a 20-fold reduction in tumor burden in the remaining mice relative to control. Mice that rejected tumors following therapy developed immunological memory against subsequent re-challenge. Our data demonstrates GITR agonist antibody activated NK cell and T lymphocyte activity, and enhanced therapeutic vaccination responses against lung cancer. PMID- 26137408 TI - STAT3 in arsenic lung carcinogenicity. AB - We recently found that the chronic sterile inflammation contributes to arsenic lung tumorigenesis which is inhibited by autophagy. STAT3 regulates the interaction between inflammation and autophagy. STAT3 may also play a critical role in mediating the crosstalk between lung epithelial cells and their microenvironment, including immune cells, during arsenic lung carcinogenesis. PMID- 26137409 TI - An adjuvanted whole cell vaccine as post-remission immunotherapy for acute leukemia. AB - Many acute leukemia patients treated with chemotherapy are at high risk of relapse without allogeneic stem cell transplantation, an immunotherapy that is limited by significant toxicity and donor availability. We propose that post remission vaccination with a simple autologous whole cell vaccine adjuvanted with alpha-galactosylceramide may be effective to prevent relapse of acute leukemia. PMID- 26137405 TI - Trial Watch: Peptide-based anticancer vaccines. AB - Malignant cells express antigens that can be harnessed to elicit anticancer immune responses. One approach to achieve such goal consists in the administration of tumor-associated antigens (TAAs) or peptides thereof as recombinant proteins in the presence of adequate adjuvants. Throughout the past decade, peptide vaccines have been shown to mediate antineoplastic effects in various murine tumor models, especially when administered in the context of potent immunostimulatory regimens. In spite of multiple limitations, first of all the fact that anticancer vaccines are often employed as therapeutic (rather than prophylactic) agents, this immunotherapeutic paradigm has been intensively investigated in clinical scenarios, with promising results. Currently, both experimentalists and clinicians are focusing their efforts on the identification of so-called tumor rejection antigens, i.e., TAAs that can elicit an immune response leading to disease eradication, as well as to combinatorial immunostimulatory interventions with superior adjuvant activity in patients. Here, we summarize the latest advances in the development of peptide vaccines for cancer therapy. PMID- 26137410 TI - Immune independent crosstalk between lymphoma and myeloid suppressor CD14+HLA DRlow/neg monocytes mediates chemotherapy resistance. AB - We have previously reported a novel phenotype of myeloid suppressors in lymphoma patients characterized by a loss of HLA-DR expression on monocytes, CD14+HLA DRlow/neg. These cells were directly immunosuppressive and were associated with poor clinical outcome. In this study, we found that lymphoma tumors could have more than 30% of their tumor occupied by CD14+ cells. This intimate spatial connection suggested substantial cell-cell communication. We examined cross talk between monocytes from healthy volunteers (normal) and lymphoma cells in co culture to identify the mechanisms and consequences of these interactions. Normal CD14+HLA-DR+ monocytes lost their HLA-DR expression after co-culture with lymphoma cells. Lymphoma-converted CD14+HLA-DRlow/neg cells exhibited similar immunosuppressive functions as CD14+HLA-DRlow/neg monocytes from lymphoma patients. Unexpectedly monocyte additions to lymphoma cell cultures protected lymphoma from cytotoxic killing by chemotherapy drug doxorubicin (DOX). Monocyte mediated resistance to DOX killing was associated with decreased Caspase-3 activity and increased anti-apoptotic heat shock protein-27 (Hsp27) expression. Soluble Hsp27 was detected in supernatant and patient plasma. Increased Hsp27 in plasma correlated with increased proportion of CD14+HLA-DRlow/neg monocytes in patient blood and was associated with lack of clinical response to DOX. This is the first report to describe a non-immune function of CD14+HLA-DRlow/neg monocytes: enhanced lymphoma resistance to chemotherapy. It is also the first report in lymphoma of Hsp27 as a potential mediator of lymphoma and monocyte crosstalk and chemotherapy resistance. Together with previous reports of the prevalence of these myeloid suppressors in other cancers, our findings identify this pathway and these interactions as a potential novel therapeutic target. PMID- 26137411 TI - Axitinib increases the infiltration of immune cells and reduces the suppressive capacity of monocytic MDSCs in an intracranial mouse melanoma model. AB - Melanoma patients are at a high risk of developing brain metastases, which are strongly vascularized and therefore have a significant risk of spontaneous bleeding. VEGF not only plays a role in neo-angiogenesis but also in the antitumor immune response. VEGFR-targeted therapy might not only have an impact on the tumor vascularization but also on tumor-infiltrating immune cells. In this study, we investigated the effect of axitinib, a small molecule TKI of VEGFR-1, 2, and -3, on tumor growth and on the composition of tumor-infiltrating immune cells in subcutaneous and intracranial mouse melanoma models. In vivo treatment with axitinib induced a strong inhibition of tumor growth and significantly improved survival in both tumor models. Characterization of the immune cells within the spleen and tumor of tumor-bearing mice respectively showed a significant increase in the number of CD3+CD8+ T cells and CD11b+ cells of axitinib-treated mice. More specifically, we observed a significant increase of intratumoral monocytic myeloid-derived suppressor cells (moMDSCs; CD11b+Ly6ChighLy6G-). Interestingly, in vitro proliferation assays showed that moMDSCs isolated from spleen or tumor of axitinib-treated mice had a reduced suppressive capacity on a per cell basis as compared to those isolated from vehicle-treated mice. Moreover, MDSCs from axitinib-treated animals displayed the capacity to stimulate allogeneic T cells. Thus, treatment with axitinib induces differentiation of moMDSC toward an antigen-presenting phenotype. Based on these observations, we conclude that the impact of axitinib on tumor growth and survival is most likely not restricted to direct anti-angiogenic effects but also involves important effects on tumor immunity. PMID- 26137412 TI - Natural Killer cell control of BRAFV600E mutant melanoma during targeted therapy. AB - Pharmacologic inhibition of the mutant BRAFV600E protein in advanced BRAFV600E melanoma results in a high proportion of patients that respond, but few with durable responses. We have recently revealed that Natural Killer (NK) cells play an essential role in the BRAFV600E inhibitor control of melanoma metastases in mice that may be therapeutically exploited to help overcome drug resistance. PMID- 26137413 TI - Splenectomy inhibits non-small cell lung cancer growth by modulating anti-tumor adaptive and innate immune response. AB - It has been shown that inhibitors of the immune system reside in the spleen and inhibit the endogenous antitumor effects of the immune system. We hypothesized that splenectomy would inhibit the growth of relatively large non-small lung cancer (NSCLC) tumors by modulating the systemic inhibition of the immune system, and in particular Myeloid Derived Suppressor Cells (MDSC). The effect of splenectomy was evaluated in several murine lung cancer models. We found that splenectomy reduces tumor growth and the development of lung metastases, but only in advanced tumors. In immune-deficient NOD-SCID mice the effect of splenectomy on tumor growth and metastatic spread disappeared. Splenectomy significantly reduced the presence of MDSC, and especially monocytic-MDSC in the circulation and inside the tumor. Specific reduction of the CCR2+ subset of monocytic MDSC was demonstrated, and the importance of the CCL2-CCR2 axis was further shown by a marked reduction in CCL2 following splenectomy. These changes were followed by changes in the macrophages contents of the tumors to become more antitumorigenic, and by increased activation of CD8+ Cytotoxic T-cells (CTL). By MDSC depletion, and adoptive transfer of MDSCs, we demonstrated that the effect of splenectomy on tumor growth was substantially mediated by MDSC cells. We conclude that the spleen is an important contributor to tumor growth and metastases, and that splenectomy can blunt this effect by depletion of MDSC, changing the amount and characteristics of myeloid cells and enhancing activation of CTL. PMID- 26137414 TI - Characterization of myeloid leukocytes and soluble mediators in pancreatic cancer: importance of myeloid-derived suppressor cells. AB - Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. PDAC cells activate tumor-specific immune responses but simultaneously trigger a strong immunosuppression. We showed that PDAC cells produce high amount of chronic inflammatory mediators and PDAC tumors build an immunosuppressive cytokine milieu, which correlates with tumor progression. We observed a low frequency of dendritic cells (DC) and a pronounced accumulation of macrophages and myeloid-derived suppressor cells (MDSC) in murine PDAC tumors. A strong accumulation of MDSC has also been demonstrated in the peripheral blood of resected PDAC patients. While DC and macrophages seem not to play a significant role in this PDAC model in the context of immunosuppression, MDSC are highly suppressive, and their accumulation is associated with an increase in intratumoral VEGF concentration during the PDAC progression. Application of the phosphodiesterase-5 inhibitor sildenafil led to a prolonged survival of PDAC bearing female mice, which was due to the decrease in MDSC frequencies and in the systemic VEGF level. This led to a restoration of anticancer immune responses, manifested in the recovery of T lymphocyte functions and in an increase in the frequency of conventional CD4+ T cells in tumors and IFNgamma level in serum of PDAC-bearing mice. Thus, MDSC are strongly involved in the PDAC-associated immunosuppression and that their depletion could create new approaches for therapy of PDAC. PMID- 26137415 TI - Myeloid STAT3 promotes formation of colitis-associated colorectal cancer in mice. AB - Myeloid cells lacking STAT3 promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deleted STAT3 in murine myeloid cells (STAT3Deltam) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3Deltam mice. Gene expression profiling showed strong activation of T cells in the stroma of STAT3Deltam CRCs. Moreover, STAT3Deltam host mice were better able to control the growth of transplanted MC38 colorectal tumor cells which are known to be killed in a T cell-dependent manner. These data suggest that myeloid cells lacking STAT3 control formation of CRCs mainly via cross activation of T cells. Interestingly, the few CRCs that formed in STAT3Deltam mice displayed enhanced stromalization but appeared normal in size indicating that they have acquired ways to escape enhanced tumor surveillance. We found that CRCs in STAT3Deltam mice consistently activate STAT3 signaling which is implicated in immune evasion and might be a target to prevent tumor relapse. PMID- 26137417 TI - Protective role of STING against gliomagenesis: Rational use of STING agonist in anti-glioma immunotherapy. AB - We recently reported that STING contributes to antiglioma immunity by triggering type I IFN induction in glioma microenvironment. Moreover, intratumoral administration of STING agonist improved the efficacy of peptide vaccination in a mouse glioma model, suggesting the rational use of STING agonists in the immunotherapy of brain tumor. PMID- 26137418 TI - CD20+ T cells have a predominantly Tc1 effector memory phenotype and are expanded in the ascites of patients with ovarian cancer. AB - Recently, a small subset of T cells that expresses the B cell marker CD20 has been identified in healthy volunteers and in patients with rheumatoid arthritis and multiple sclerosis. The origin of these CD20-positive T cells as well as their relevance in human disease remains unclear. Here, we identified that after functional B cell/T cell interaction CD20 molecules are transferred to the cell surface of T cells by trogocytosis together with the established trogocytosis marker HLA-DR. Further, the presence of CD20 on isolated CD20+ T cells remained stable for up to 48h of ex vivo culture. These CD20+ T cells almost exclusively produced IFNgamma (~70% vs. ~20% in the CD20- T cell population) and were predominantly (CD8+) effector memory T cells (~60-70%). This IFNgamma producing and effector memory phenotype was also determined for CD20+ T cells as detected in the peripheral blood and ascitic fluids of ovarian cancer (OC) patients. In the latter, the percentage of CD20+ T cells was further strongly increased (from ~6% in peripheral blood to 23% in ascitic fluid). Taken together, the data presented here indicate that CD20 is transferred to T cells upon intimate T cell/B cell interaction. Further, CD20+ T cells are of memory and IFNgamma producing phenotype and are present in increased amounts in ascitic fluid of OC patients. PMID- 26137419 TI - Metabolic disorders with clinical and radiologic features of sporadic Creutzfeldt Jakob disease. AB - Two patients with metabolic disorders presented with clinical and radiologic features suggestive of sporadic Creutzfeldt-Jakob disease (sCJD). Case 1 was a 50 year-old man with rapid decline in cognitive, behavioral, and motor function following new-onset seizures. MRI was read as consistent with CJD, and he was referred for a treatment trial, but it was determined that he recently experienced rapid correction of hyponatremia resulting in extrapontine myelinolysis. Case 2 was a 66-year-old woman with poorly controlled diabetes mellitus who was found unconscious after a suspected insulin overdose. Examination showed altered mental status and neuroimaging was remarkable for cortical/striatal hyperintensities suggestive of sCJD. On autopsy, she had hypoglycemic/hypoxic nerve cell loss. Although characteristic MRI findings have high sensitivity and specificity for sCJD, potentially reversible metabolic disorders sometimes present rapidly and can resemble sCJD both clinically and radiologically. These cases highlight the importance of establishing a broad differential diagnosis when evaluating a patient with suspected sCJD. PMID- 26137420 TI - Comparing CSF biomarkers and brain MRI in the diagnosis of sporadic Creutzfeldt Jakob disease. AB - We assessed the diagnostic utility of 3 CSF biomarkers-14-3-3 protein, total tau (T-tau), and neuron-specific enolase (NSE)-from the same lumbar puncture to distinguish between participants with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease (sCJD, n = 57) and controls with nonprion rapidly progressive dementia (npRPD, n = 41). Measures of diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value, as well as logistic regression and area under the receiver operator curve (AUC), were used to assess the ability of these CSF biomarkers, alone or concomitantly, to predict diagnosis. In a subcohort with available MRI (sCJD n = 57, npRPD = 32), we compared visual assessment of diffusion-weighted imaging MRI sequences to these CSF biomarkers. MRI was the best predictor, with an AUC of 0.97 (confidence interval [CI] 0.92-1.00) and a diagnostic accuracy of 97% (CI 90%-100%). Of the CSF biomarkers, T-tau had a higher diagnostic accuracy (79.6%) than 14-3-3 (70.4%, CI for difference 8.7%, 9.7%; p = 0.048) or NSE (71.4%, CI for difference 7.6%, 8.7%; p = 0.03). PMID- 26137421 TI - Multiple sclerosis in US minority populations: Clinical practice insights. AB - The heterogeneity of multiple sclerosis (MS) characteristics among various ethnic minority populations is a topic of recent interest. However, these populations are consistently underrepresented in clinical trials, leading to limited data on the effectiveness of treatments in these groups of patients and lack of an evidence-based approach to treatment. In order to achieve optimal disease management in the ethnic minority MS populations, a better understanding of the regional, socioeconomic, and cultural influences that result in underrepresentation of these groups in clinical trials is needed. Furthermore, it would be beneficial to identify the genetic factors that influence disease disparity in these minority populations. Suggestions for the identification and implementation of best practices for fostering the trust of ethnic minority patients with MS and enhancing their participation in clinical trials are offered. PMID- 26137422 TI - The demise of direct ophthalmoscopy: A modern clinical challenge. AB - Ocular funduscopy appears to be a dying art. Physicians and medical students alike lack confidence in the use of an ophthalmoscope. As a result, few clinicians perform ophthalmoscopy, and many who do are unable to reliably detect abnormalities of the ocular fundus. Approaches to remediation in undergraduate medical education have included simulators, longitudinal skill reinforcement, Web based teaching, and other techniques. Preservation of the ophthalmoscopic art has been hindered by technical difficulty, waning enthusiasm for ophthalmoscopy, and even discouragement from preceptors in medical education. Ocular fundus photography may serve a role in medical education to help improve student confidence in interpretation of ocular fundus findings and improve awareness of the importance of examination of the ocular fundus. Because neurology clerkships and clinical practices remain an important forum for honing ocular funduscopy skills, the neurologist should be familiar with novel alternative techniques that facilitate examination of the ocular fundus. PMID- 26137416 TI - Consensus nomenclature for CD8+ T cell phenotypes in cancer. AB - Whereas preclinical investigations and clinical studies have established that CD8+ T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8+ T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8+ T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8+ T cell immunity, leading to the emergence of dysfunctional CD8+ T cells. The existence of different types of CD8+ T cells in cancer calls for a more precise definition of the CD8+ T cell immune phenotypes in cancer and the abandonment of the generic terms "pro-tumor" and "antitumor." Based on recent studies investigating the functions of CD8+ T cells in cancer, we here propose some guidelines to precisely define the functional states of CD8+ T cells in cancer. PMID- 26137423 TI - "Metastatic" embolic lesions and enlarging pseudoaneurysms associated with cardiac myxoma. PMID- 26137424 TI - Asymptomatic myelitis in neuromyelitis optica and autoimmune aquaporin-4 channelopathy. PMID- 26137425 TI - A reappraisal of the Middle Triassic chirotheriid Chirotherium ibericus Navas, 1906 (Iberian Range NE Spain), with comments on the Triassic tetrapod track biochronology of the Iberian Peninsula. AB - Triassic vertebrate tracks are known from the beginning of the 19th century and have a worldwide distribution. Several Triassic track ichnoassemblages and ichnotaxa have a restricted stratigraphic range and are useful in biochronology and biostratigraphy. The record of Triassic tracks in the Iberian Peninsula has gone almost unnoticed although more than 25 localities have been described since 1897. In one of these localities, the naturalist Longinos Navas described the ichnotaxon Chirotherium ibericus in 1906.The vertebrate tracks are in two sandy slabs from the Anisian (Middle Triassic) of the Moncayo massif (Zaragoza, Spain). In a recent revision, new, previously undescribed vertebrate tracks have been identified. The tracks considered to be C. ibericus as well as other tracks with the same morphology from both slabs have been classified as Chirotherium barthii. The rest of the tracks have been assigned to Chirotheriidae indet., Rhynchosauroides isp. and undetermined material. This new identification of C. barthii at the Navas site adds new data to the Iberian record of this ichnotaxon, which is characterized by the small size of the tracks when compared with the main occurrences of this ichnotaxon elsewhere. As at the Navas tracksite, the Anisian C. barthii-Rhynchosauroides ichnoassemblage has been found in other coeval localities in Iberia and worldwide. This ichnoassemblage belongs to the upper Olenekian-lower Anisian interval according to previous biochronological proposals. Analysis of the Triassic Iberian record of tetrapod tracks is uneven in terms of abundance over time. From the earliest Triassic to the latest Lower Triassic the record is very scarce, with Rhynchosauroides being the only known ichnotaxon. Rhynchosauroides covers a wide temporal range and gives poor information for biochronology. The record from the uppermost Lower Triassic to the Middle Triassic is abundant. The highest ichnodiversity has been reported for the Anisian with an assemblage composed of Dicynodontipus, Procolophonichnium, Rhynchosauroides, Rotodactylus, Chirotherium, Isochirotherium, Coelurosaurichnus and Paratrisauropus. The Iberian track record from the Anisian is coherent with the global biochronology proposed for Triassic tetrapod tracks. Nevertheless, the scarcity of track occurrences during the late Olenekian and Ladinian prevents analysis of the corresponding biochrons. Finally, although the Iberian record for the Upper Triassic is not abundant, the presence of Eubrontes, Anchisauripus and probably Brachychirotherium is coherent with the global track biochronology as well. Thus, the Triassic track record in the Iberian Peninsula matches the expected record for this age on the basis of a global biochronological approach, supporting the idea that vertebrate Triassic tracks are a useful tool in biochronology. PMID- 26137426 TI - Weather conditions associated with autumn migration by mule deer in Wyoming. AB - Maintaining ecological integrity necessitates a proactive approach of identifying and acquiring lands to conserve unfragmented landscapes, as well as evaluating existing mitigation strategies to increase connectivity in fragmented landscapes. The increased use of highway underpasses and overpasses to restore connectivity for wildlife species offers clear conservation benefits, yet also presents a unique opportunity to understand how weather conditions may impact movement of wildlife species. We used remote camera observations (19,480) from an existing wildlife highway underpass in Wyoming and daily meteorological observations to quantify weather conditions associated with autumn migration of mule deer in 2009 and 2010. We identified minimal daily temperature and snow depth as proximate cues associated with mule deer migration to winter range. These weather cues were consistent across does and bucks, but differed slightly by year. Additionally, extreme early season snow depth or cold temperature events appear to be associated with onset of migration. This information will assist wildlife managers and transportation officials as they plan future projects to maintain and enhance migration routes for mule deer. PMID- 26137427 TI - Delivery by caesarean section and risk of childhood obesity: analysis of a Peruvian prospective cohort. AB - Objectives. We aimed to assess if Caesarean section is a risk factor for overnutrition in early- and late-childhood, and to assess the magnitude of the effect of child- versus family-related variables in these risk estimates. Methods. Longitudinal data from Peruvian children from the Young Lives Study was used. Outcomes assessed were overweight, obesity, overnutrition (overweight plus obesity), and central obesity (waist circumference) at the age 5 (first follow up) and 7 (second follow-up) years. The exposure of interests was delivery by Caesarean section. Relative risks (RR) and 95% confidence intervals (95% CI) were calculated using multivariable models adjusted for child-related (e.g., birth weight) and family-related (e.g., maternal nutritional status) variables. Results. At baseline, mean age was 11.7 (+/- 3.5) months and 50.1% were boys. Children born by Caesarean section were 15.6%. The 10.5% of the children were overweight and 2.4% were obese. For the obesity outcome, data from 6,038 and 9,625 children-years was included from baseline to the first and second follow up, respectively. Compared to those who did not experience Caesarean delivery, the risk of having obesity was higher in the group born by Caesarean: RRs were higher at early-childhood (first follow-up: 2.25; 95% CI [1.36-3.74]) than later in life (second follow-up: 1.57; 95% CI [1.02-2.41]). Family-related variables had a greater effect in attenuating the risk estimates for obesity at the first, than at the second follow-up. Conclusion. Our results suggest a higher probability of developing obesity, but not overweight, among children born by Caesarean section delivery. The magnitude of risk estimates decreased over time, and family-related variables had a stronger effect on the risk estimates at early childhood. PMID- 26137428 TI - Metabarcoding dietary analysis of coral dwelling predatory fish demonstrates the minor contribution of coral mutualists to their highly partitioned, generalist diet. AB - Understanding the role of predators in food webs can be challenging in highly diverse predator/prey systems composed of small cryptic species. DNA based dietary analysis can supplement predator removal experiments and provide high resolution for prey identification. Here we use a metabarcoding approach to provide initial insights into the diet and functional role of coral-dwelling predatory fish feeding on small invertebrates. Fish were collected in Moorea (French Polynesia) where the BIOCODE project has generated DNA barcodes for numerous coral associated invertebrate species. Pyrosequencing data revealed a total of 292 Operational Taxonomic Units (OTU) in the gut contents of the arc-eye hawkfish (Paracirrhites arcatus), the flame hawkfish (Neocirrhites armatus) and the coral croucher (Caracanthus maculatus). One hundred forty-nine (51%) of them had species-level matches in reference libraries (>98% similarity) while 76 additional OTUs (26%) could be identified to higher taxonomic levels. Decapods that have a mutualistic relationship with Pocillopora and are typically dominant among coral branches, represent a minor contribution of the predators' diets. Instead, predators mainly consumed transient species including pelagic taxa such as copepods, chaetognaths and siphonophores suggesting non random feeding behavior. We also identified prey species known to have direct negative interactions with stony corals, such as Hapalocarcinus sp, a gall crab considered a coral parasite, as well as species of vermetid snails known for their deleterious effects on coral growth. Pocillopora DNA accounted for 20.8% and 20.1% of total number of sequences in the guts of the flame hawkfish and coral croucher but it was not detected in the guts of the arc-eye hawkfish. Comparison of diets among the three fishes demonstrates remarkable partitioning with nearly 80% of prey items consumed by only one predator. Overall, the taxonomic resolution provided by the metabarcoding approach highlights a highly complex interaction web and demonstrates that levels of trophic partitioning among coral reef fishes have likely been underestimated. Therefore, we strongly encourage further empirical approaches to dietary studies prior to making assumptions of trophic equivalency in food web reconstruction. PMID- 26137429 TI - Family structure as a predictor of screen time among youth. AB - The family plays a central role in the development of health-related behaviors among youth. The objective of this study was to determine whether non-traditional parental structure and shared custody arrangements predict how much time youth spend watching television, using a computer recreationally, and playing video games. Participants were a nationally representative sample of Canadian youth (N = 26,068) in grades 6-10 who participated in the 2009/10 Health Behaviour in School-aged Children Survey. Screen time in youth from single parent and reconstituted families, with or without regular visitation with their non residential parent, was compared to that of youth from traditional dual-parent families. Multiple imputation was used to account for missing data. After multiple imputation, the relative odds of being in the highest television, computer use, video game, and total screen time quartiles were not different in boys and girls from non-traditional families by comparison to boys and girls from traditional dual-parent families. In conclusion, parental structure and child custody arrangements did not have a meaningful impact on screen time among youth. PMID- 26137430 TI - Parents' evaluation of support in Australian hospitals following stillbirth. AB - The present study evaluated the level of support and satisfaction among parents of stillborn babies in Australian hospitals. One-hundred and eighty-nine mothers and fathers completed an online survey designed by the researcher based on the guidelines designed by the Perinatal Society of Australia and New Zealand. Support was inconsistent with guidelines implemented on average only 55% of the time. Areas of support regarding creating memories, birth options and autopsy were most problematic. A significant positive correlation was found between support and satisfaction and there is indication that there has been some increase in support and satisfaction over time. There has been a significant increase in both support and satisfaction since the release of the guidelines in 2009. Creating memories was regarded by parents as the most influential to their grief. It is recommended that health professionals review guidelines and seek feedback from parents as to how they can improve the support they provide. PMID- 26137431 TI - Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitis. AB - Objective. Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods. Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75% of nasal swabs. Results. SA nasal carriage did not change during RTX (p = 0.297). However, the rate of positive nasal swabs in GPA patients with transient SA nasal carriage during RTX maintenance increased from 0 prior RTX to 0.42 during RTX (p = 0.017). Persistent SA nasal carriage did not increase the risk of relapses (p = 0.844), of hypogammaglobulinemia (p = 0.122) and of severe infections (p = 0.144), but reduced the risk of chronic infections (p = 0.044). Change in SA carriage status during RTX did not influence the risk of relapses (p = 0.756), hypogammaglobulinamia (p = 0.474) and infections, either severe (p = 0.913) or chronic (p = 0.121). Conclusion. Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not seem to increase the risk of relapses, but seemed to decrease the risk of hypogammaglobulinemia associated chronic infections. PMID- 26137432 TI - Decreasing seagrass density negatively influences associated fauna. AB - Seagrass meadows globally are disappearing at a rapid rate with physical disturbances being one of the major drivers of this habitat loss. Disturbance of seagrass can lead to fragmentation, a reduction in shoot density, canopy height and coverage, and potentially permanent loss of habitat. Despite being such a widespread issue, knowledge of how such small scale change affects the spatial distribution and abundances of motile fauna remains limited. The present study investigated fish and macro faunal community response patterns to a range of habitat variables (shoot length, cover and density), including individual species habitat preferences within a disturbed and patchy intertidal seagrass meadow. Multivariate analysis showed a measurable effect of variable seagrass cover on the abundance and distribution of the fauna, with species specific preferences to both high and low seagrass cover seagrass. The faunal community composition varied significantly with increasing/decreasing cover. The faunal species composition of low cover seagrass was more similar to sandy control plots than to higher cover seagrass. Shannon Wiener Diversity (H') and species richness was significantly higher in high cover seagrass than in low cover seagrass, indicating increasing habitat value as density increases. The results of this study underline how the impacts of small scale disturbances from factors such as anchor damage, boat moorings and intertidal vehicle use on seagrass meadows that reduce shoot density and cover can impact upon associated fauna. These impacts have negative consequences for the delivery of ecosystem services such as the provision of nursery habitat. PMID- 26137433 TI - Imbalance in the blood antioxidant system in growth hormone-deficient children before and after 1 year of recombinant growth hormone therapy. AB - The aim of our study was to examine the effects of 12-month therapy with recombinant growth hormone (rGH) on the blood antioxidant system in children with growth hormone deficiency (GHD). Total antioxidant capacity (TAC) of plasma was measured by FRAP (ferric reducing antioxidant power or ferric reducing ability of plasma); activities of superoxide dismutase (SOD) and catalase (CAT) in erythrocytes were assessed; non-protein thiols (NT) and ceruloplasmin (CP) levels were also measured. These parameters were determined before and after 12 month of rGH treatment. Eleven treatment-naive prepubertal children with growth hormone deficiency were included in the study. Another 11 prepubertal children comprised a control group. Before rGH treatment, TAC of plasma and NT level in the control group were significantly lower (726 +/- 196 vs. 525 +/- 166 umol/L, P = 0.0182 and 0.92 +/- 0.18 vs. 0.70 +/- 0.22 umol/ml, P = 0.0319, before and after the therapy, respectively). The only parameter that significantly (19.6 +/- 4.7 vs. 14.5 +/- 3.4 Units/g Hb, P = 0.0396) exceeded the same in the control group after rGH therapy was SOD activity. However, none of the measured parameters of antioxidant system in GHD children, except for TAC (525 +/- 166 vs. 658 +/- 115 umol/L, P = 0.0205), exhibited significant improvement toward the end of the 12 month treatment period, although non-significant changes in CAT activity and CP level were also observed. This work has demonstrated that some parameters of the blood antioxidant system are out of balance and even impaired in GHD children. A 12-month treatment with rGH resulted in a partial improvement of the antioxidant system. PMID- 26137434 TI - HaloTag is an effective expression and solubilisation fusion partner for a range of fibroblast growth factors. AB - The production of recombinant proteins such as the fibroblast growth factors (FGFs) is the key to establishing their function in cell communication. The production of recombinant FGFs in E. coli is limited, however, due to expression and solubility problems. HaloTag has been used as a fusion protein to introduce a genetically-encoded means for chemical conjugation of probes. We have expressed 11 FGF proteins with an N-terminal HaloTag, followed by a tobacco etch virus (TEV) protease cleavage site to allow release of the FGF protein. These were purified by heparin-affinity chromatography, and in some instances by further ion exchange chromatography. It was found that HaloTag did not adversely affect the expression of FGF1 and FGF10, both of which expressed well as soluble proteins. The N-terminal HaloTag fusion was found to enhance the expression and yield of FGF2, FGF3 and FGF7. Moreover, whereas FGF6, FGF8, FGF16, FGF17, FGF20 and FGF22 were only expressed as insoluble proteins, their N-terminal HaloTag fusion counterparts (Halo-FGFs) were soluble, and could be successfully purified. However, cleavage of Halo-FGF6, -FGF8 and -FGF22 with TEV resulted in aggregation of the FGF protein. Measurement of phosphorylation of p42/44 mitogen-activated protein kinase and of cell growth demonstrated that the HaloTag fusion proteins were biologically active. Thus, HaloTag provides a means to enhance the expression of soluble recombinant proteins, in addition to providing a chemical genetics route for covalent tagging of proteins. PMID- 26137435 TI - Prognostic value of neutrophil-to-lymphocyte ratio in breast cancer. AB - Inflammation is an essential component of pathogenesis and progression of cancer. A high neutrophil-to-lymphocyte ratio (NLR) is considered as a prognostic indicator for breast cancer. This meta-analysis was conducted to establish the overall accuracy of the NLR test in the diagnosis of breast cancer. A comprehensive search of the literature was conducted by using PubMed, Web of Science and China National Knowledge Infrastructure (CNKI). Published studies dating up to July 2014 and 4,293 patients were enrolled in the present study. In order to evaluate the association between NLR and overall survival (OS), disease free survival (DFS), recurrence-free survival (RFS) or cancer specific survival (CSS), the hazard ratios (HRs) and their 95% confidence intervals (CIs) were extracted. OS was the primary outcome. The results suggested that increased NLR was a strong predictor for OS with HR of 2.28 (95% CI = 1.08-4.80, Pheterogeneity < 0.001). Stratified analyses indicated that a high NLR appeared to be a negative prognostic marker in Caucasian populations (HR = 4.53, 95% CI = 3.11-6.60, Pheterogeneity = 0.096), multivariate analysis method (HR = 2.10, 95% CI = 1.52 2.89, Pheterogeneity = 0.591), and mixed metastasis (HR = 4.53, 95% CI = 3.11 6.60, Pheterogeneity = 0.096). Elevated NLR was associated with a high risk for DFS (HR = 1.38, 95% CI = 1.09-1.74, Pheterogeneity = 0.050) and in subgroups of multivariate analysis (HR = 1.64, 95% CI = 1.25-2.14, Pheterogeneity = 0.545) and mixed metastasis (HR = 1.99, 95% CI = 1.28-3.09, Pheterogeneity = 0.992). In summary, NLR could be considered as a predictive factor for patients with breast cancer. PMID- 26137436 TI - Uncleavable Nup98-Nup96 is functional in the fission yeast Schizosaccharomyces pombe. AB - Essential nucleoporins Nup98 and Nup96 are coded by a single open reading frame, and produced by autopeptidase cleavage. The autocleavage site of Nup98-Nup96 is highly conserved in a wide range of organisms. To understand the importance of autocleavage, we examined a mutant that produces the Nup98-Nup96 joint molecule as a sole protein product of the nup189 (+) gene in the fission yeast Schizosaccharomyces pombe. Cells expressing only the joint molecule were found to be viable. This result indicates that autocleavage of Nup98-Nup96 is dispensable for cell growth, at least under normal culture conditions in S. pombe. PMID- 26137437 TI - Colletotrichum truncatum species complex: Treatment considerations and review of the literature for an unusual pathogen causing fungal keratitis and endophthalmitis. AB - We present a case of Colletotrichum truncatum species complex fungal keratitis and endophthalmitis in an 87-year-old immunocompetent male in whom oral triazole antifungals were contraindicated. The patient had recently returned from 4 months in Jamaica with a one month history of progressively increasing pain and inflammation in his left eye. Corneal samples grew a filamentous fungus and internal transcribed spacer sequencing polymerase chain reaction confirmed the presence of C. truncatum species complex. Samples showed no microbial growth. PMID- 26137438 TI - A major role of insulin in promoting obesity-associated adipose tissue inflammation. AB - OBJECTIVE: Adipose tissue (AT) inflammation is associated with systemic insulin resistance and hyperinsulinemia in obese rodents and humans. A longstanding concept is that hyperinsulinemia may promote systemic insulin resistance through downregulation of its receptor on target tissues. Here we tested the novel hypothesis that insulin also impairs systemic insulin sensitivity by specifically enhancing adipose inflammation. METHODS: Circulating insulin levels were reduced by about 50% in diet-induced and genetically obese mice by treatments with diazoxide or streptozotocin, respectively. We then examined AT crown-like structures, macrophage markers and pro-inflammatory cytokine expression in AT. AT lipogenesis and systemic insulin sensitivity was also monitored. Conversely, insulin was infused into lean mice to determine its affects on the above parameters. RESULTS: Lowering circulating insulin levels in obese mice by streptozotocin treatment decreased macrophage content in AT, enhancing insulin stimulated Akt phosphorylation and de novo lipogenesis (DNL). Moreover, responsiveness of blood glucose levels to injected insulin was improved by streptozotocin and diazoxide treatments of obese mice without changes in body weight. Remarkably, even in lean mice, infusion of insulin under constant euglycemic conditions stimulated expression of cytokines in AT. Consistent with these findings, insulin treatment of 3T3-L1 adipocytes caused a 10-fold increase in CCL2 mRNA levels within 6 h, which was blocked by the ERK inhibitor PD98059. CONCLUSION: Taken together, these results indicate that obesity-associated hyperinsulinemia unexpectedly drives AT inflammation in obese mice, which in turn contributes to factors that suppress insulin-stimulated adipocyte DNL and systemic insulin sensitivity. PMID- 26137439 TI - Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes. AB - OBJECTIVE: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type-2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs. MUHO), opening the possibility that FGF21 is a cross talker between liver and adipose tissue in MUHO. Furthermore, we studied the effects of chronic FGF21 treatment on adipocyte differentiation, lipid storage, and adipokine secretion. METHODS: In 20 morbidly obese donors of abdominal subcutaneous fat biopsies discordant for their whole-body insulin sensitivity (hereby classified as MHO or MUHO subjects), serum FGF21 was quantified. The impact of chronic FGF21 treatment on differentiation, lipid accumulation, and adipokine release was assessed in isolated preadipocytes differentiated in vitro. RESULTS: Serum FGF21 concentrations were more than two-fold higher in MUHO as compared to MHO subjects (457 +/- 378 vs. 211 +/- 123 pg/mL; p < 0.05). FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p < 0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, -15% and -40%, respectively; p < 0.01 both), reduced adiponectin expression (-20%; p < 0.05), markedly reduced adiponectin release (-60%; p < 0.01), and substantially increased leptin (+60%; p < 0.01) and interleukin-6 (+50%; p < 0.001) release. CONCLUSIONS: The hepatokine FGF21 exerts weak lipogenic and anti-adipogenic actions and marked adiponectin suppressive and leptin and interleukin-6 release-promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes. PMID- 26137441 TI - Genetic disruption of uncoupling protein 1 in mice renders brown adipose tissue a significant source of FGF21 secretion. AB - OBJECTIVE: Circulating fibroblast growth factor 21 (FGF21) is an important auto- and endocrine player with beneficial metabolic effects on obesity and diabetes. In humans, thermogenic brown adipose tissue (BAT) was recently suggested as a source of FGF21 secretion during cold exposure. Here, we aim to clarify the role of UCP1 and ambient temperature in the regulation of FGF21 in mice. METHODS: Wildtype (WT) and UCP1-knockout (UCP1 KO) mice, the latter being devoid of BAT derived non-shivering thermogenesis, were exposed to different housing temperatures. Plasma metabolites and FGF21 levels were determined, gene expression was analyzed by qPCR, and tissue histology was performed with adipose tissue. RESULTS: At thermoneutrality, FGF21 gene expression and serum levels were not different between WT and UCP1 KO mice. Cold exposure led to highly increased FGF21 serum levels in UCP1 KO mice, which were reflected in increased FGF21 gene expression in adipose tissues but not in liver and skeletal muscle. Ex vivo secretion assays revealed FGF21 release only from BAT, progressively increasing with decreasing ambient temperatures. In association with increased FGF21 serum levels in the UCP1 KO mouse, typical FGF21-related serum metabolites and inguinal white adipose tissue morphology and thermogenic gene expression were altered. CONCLUSIONS: Here we show that the genetic ablation of UCP1 increases FGF21 gene expression in adipose tissue. The removal of adaptive nonshivering thermogenesis renders BAT a significant source of endogenous FGF21 under thermal stress. Thus, the thermogenic competence of BAT is not a requirement for FGF21 secretion. Notably, high endogenous FGF21 levels in UCP1-deficient models and subjects may confound pharmacological FGF21 treatments. PMID- 26137440 TI - Peroxisome proliferator-activated receptor alpha plays a crucial role in behavioral repetition and cognitive flexibility in mice. AB - BACKGROUND/OBJECTIVES: Nuclear peroxisome proliferator activated receptor-alpha (PPAR-alpha) plays a fundamental role in the regulation of lipid homeostasis and is the target of medications used to treat dyslipidemia. However, little is known about the role of PPAR-alpha in mouse behavior. METHODS: To investigate the function of Ppar-alpha in cognitive functions, a behavioral phenotype analysis of mice with a targeted genetic disruption of Ppar-alpha was performed in combination with neuroanatomical, biochemical and pharmacological manipulations. The therapeutic exploitability of PPAR-alpha was probed in mice using a pharmacological model of psychosis and a genetic model (BTBR T + tf/J) exhibiting a high rate of repetitive behavior. RESULTS: An unexpected role for brain Ppar alpha in the regulation of cognitive behavior in mice was revealed. Specifically, we observed that Ppar-alpha genetic perturbation promotes rewiring of cortical and hippocampal regions and a behavioral phenotype of cognitive inflexibility, perseveration and blunted responses to psychomimetic drugs. Furthermore, we demonstrate that the antipsychotic and autism spectrum disorder (ASD) medication risperidone ameliorates the behavioral profile of Ppar-alpha deficient mice. Importantly, we reveal that pharmacological PPAR-alpha agonist treatment in mice improves behavior in a pharmacological model of ketamine-induced behavioral dysinhibition and repetitive behavior in BTBR T + tf/J mice. CONCLUSION: Our data indicate that Ppar-alpha is required for normal cognitive function and that pharmacological stimulation of PPAR-alpha improves cognitive function in pharmacological and genetic models of impaired cognitive function in mice. These results thereby reveal an unforeseen therapeutic application for a class of drugs currently in human use. PMID- 26137442 TI - Notch intracellular domain overexpression in adipocytes confers lipodystrophy in mice. AB - OBJECTIVE: The Notch family of intermembrane receptors is highly conserved across species and is involved in cell fate and lineage control. Previous in vitro studies have shown that Notch may inhibit adipogenesis. Here we describe the role of Notch in adipose tissue by employing an in vivo murine model which overexpresses Notch in adipose tissue. METHODS: Albino C57BL/6J Rosa(NICD/NICD)::Adipoq-Cre (Ad-NICD) male mice were generated to overexpress the Notch intracellular domain (NICD) specifically in adipocytes. Male Rosa(NICD/NICD) mice were used as controls. Mice were evaluated metabolically at the ages of 1 and 3 months by assessing body weights, serum metabolites, body composition (EchoMRI), glucose tolerance and insulin tolerance. Histological sections of adipose tissue depots as well as of liver were examined. The mRNA expression profile of genes involved in adipogenesis was analyzed by quantitative real-time PCR. RESULTS: The Ad-NICD mice were heavier with significantly lower body fat mass compared to the controls. Small amounts of white adipose tissue could be seen in the 1-month old Ad-NICD mice, but was almost absent in the 3 months old mice. The Ad-NICD mice also had higher serum levels of glucose, insulin, triglyceride and non-esterified fatty acids. These differences were more prominent in the older (3-months) than in the younger (1-month) mice. The Ad-NICD mice also showed severe insulin resistance along with a steatotic liver. Gene expression analysis in the adipose tissue depots showed a significant repression of lipogenic (Fasn, Acacb) and adipogenic pathways (C/ebpalpha, C/ebpbeta, Ppargamma2, Srebf1). CONCLUSIONS: Increased Notch signaling in adipocytes in mice results in blocked expansion of white adipose tissue which leads to ectopic accumulation of lipids and insulin resistance, thus to a lipodystrophic phenotype. These results suggest that further investigation of the role of Notch signaling in adipocytes could lead to the manipulation of this pathway for therapeutic interventions in metabolic disease. PMID- 26137443 TI - Putamen-midbrain functional connectivity is related to striatal dopamine transporter availability in patients with Lewy body diseases. AB - Prior work has shown that functional connectivity between the midbrain and putamen is altered in patients with impairments in the dopamine system. This study examines whether individual differences in midbrain-striatal connectivity are proportional to the integrity of the dopamine system in patients with nigrostriatal dopamine loss (Parkinson's disease and dementia with Lewy bodies). We assessed functional connectivity of the putamen during resting state fMRI and dopamine transporter (DAT) availability in the striatum using 11C-Altropane PET in twenty patients. In line with the hypothesis that functional connectivity between the midbrain and the putamen reflects the integrity of the dopaminergic neurotransmitter system, putamen-midbrain functional connectivity was significantly correlated with striatal DAT availability even after stringent control for effects of head motion. DAT availability did not relate to functional connectivity between the caudate and thalamus/prefrontal areas. As such, resting state functional connectivity in the midbrain-striatal pathway may provide a useful indicator of underlying pathology in patients with nigrostriatal dopamine loss. PMID- 26137444 TI - Network analysis of EEG related functional MRI changes due to medication withdrawal in focal epilepsy. AB - Anti-epileptic drugs (AEDs) have a global effect on the neurophysiology of the brain which is most likely reflected in functional brain activity recorded with EEG and fMRI. These effects may cause substantial inter-subject variability in studies where EEG correlated functional MRI (EEG-fMRI) is used to determine the epileptogenic zone in patients who are candidate for epilepsy surgery. In the present study the effects on resting state fMRI are quantified in conditions with AED administration and after withdrawal of AEDs. EEG-fMRI data were obtained from 10 patients in the condition that the patient was on the steady-state maintenance doses of AEDs as prescribed (condition A) and after withdrawal of AEDs (condition B), at the end of a clinically standard pre-surgical long term video-EEG monitoring session. Resting state networks (RSN) were extracted from fMRI. The epileptic component (ICE) was identified by selecting the RSN component with the largest overlap with the EEG-fMRI correlation pattern. Changes in RSN functional connectivity between conditions A and B were quantified. EEG-fMRI correlation analysis was successful in 30% and 100% of the cases in conditions A and B, respectively. Spatial patterns of ICEs are comparable in conditions A and B, except for one patient for whom it was not possible to identify the ICE in condition A. However, the resting state functional connectivity is significantly increased in the condition after withdrawal of AEDs (condition B), which makes resting state fMRI potentially a new tool to study AED effects. The difference in sensitivity of EEG-fMRI in conditions A and B, which is not related to the number of epileptic EEG events occurring during scanning, could be related to the increased functional connectivity in condition B. PMID- 26137445 TI - ADIPOQ single nucleotide polymorphism: Association with adiponectin and lipoproteins levels restricted to men. AB - Adiponectin is an adipokine inversely correlated with obesity, which has beneficial effect on insulin resistance and lipid metabolism. Considering its potential as a therapeutic target in the metabolic disorder contexts, and in order to add knowledge in the area, our study evaluated the ADIPOQ 276G > T polymorphism effect on adiponectin levels, and on lipoproteins of clinical interest in a population sample composed of 211 healthy individuals. Significant effects were observed only among men: the carriers of heterozygous genotype (GT) showed high levels of adiponectin (p = 0.018), while the rare homozygous genotype (TT) gave its carriers a negative phenotype, represented by higher levels of low density lipoprotein cholesterol (LDL-C) (p = 0.004 and p = 0.005) and total cholesterol (TC) (p = 0.010 and p = 0.005) compared to carriers of other genotypes (GG and GT respectively), the independent effect of SNP on LDL-C and TC levels was confirmed by multiple regression analysis (p = 0.008 and p = 0.044). We found no evidence of correlation between circulating adiponectin levels and biochemical markers, which suggests, therefore, an SNP 276G > T independent effect on adiponectin levels and on lipoprotein metabolism in men enrolled in this study. PMID- 26137446 TI - Assembly and variation analyses of Clarias batrachus mitogenome retrieved from WGS data and its phylogenetic relationship with other catfishes. AB - Whole genome sequencing (WGS) using next generation sequencing technologies paves the way to sequence the mitochondrial genomes with greater ease and lesser time. Here, we used the WGS data of Clarias batrachus, generated from Roche 454 and Ion Torrent sequencing platforms, to assemble the complete mitogenome using both de novo and reference based approaches. Both the methods yielded almost similar results and the best assembled mitogenome was of 16,510 bp size (GenBank Acc. No. KM259918). The mitogenome annotation resulted in 13 coding genes, 22 tRNA genes, 2 rRNA genes and one control region, and the gene order was found to be identical with other catfishes. Variation analyses between assembled and the reference (GenBank Acc. No. NC_023923) mitogenome revealed 51 variations. The phylogenetic analysis of coding DNA sequences and tRNA supports the monophyly of catfishes. Two SSRs were identified in C. batrachus mitogenome, out of which one was unique to this species. Based on the relative rate of gene evolution, protein coding mitochondrial genes were found to evolve at a much faster pace than the d-loop, which in turn are followed by the rRNAs; the tRNAs showed wide variability in the rate of sequence evolution, and on average evolve the slowest. Among the coding genes, ND2 evolves most rapidly. The variations present in the coding regions of the mitogenome and their comparative analyses with other catfish species may be useful in species conservation and management programs. PMID- 26137447 TI - Role of glutathione S-transferase M1, T1 and P1 gene polymorphisms in childhood acute lymphoblastic leukemia susceptibility in a Turkish population. AB - The variations between different individuals in the xenobiotic metabolizing enzymes' activity were shown to modify susceptibility to childhood acute lymphoblastic leukemia (ALL). Polymorphisms associated with genes coding for the glutathione S-transferase (GST) enzyme were known to affect the metabolism of different carcinogens. The aim of this study was to evaluate the influence of the GSTM1 and GSTT1 deletion polymorphisms, and the GSTP1 Ile105Val single nucleotide polymorphism (SNP) on the susceptibility to childhood ALL. The study was conducted in 95 children with ALL and 190 healthy control subjects from the Turkish population. The data revealed no difference in the prevalence of the GSTM1 and GSTT1 null genotypes between the childhood ALL patients and the controls. No association was found between GSTP1 Ile105Val variants and the susceptibility to childhood ALL, separately or in combination. Our findings suggested that the status of heritable GST polymorphism might not influence the risk of developing childhood ALL. Studies with a larger sample size are needed to evaluate and confirm the validity of our results. PMID- 26137449 TI - Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth. AB - BRAF and MEK inhibitors have improved outcomes for patients with BRAF-mutant melanoma, but their efficacy is limited by both intrinsic and acquired resistances. Activation of the PI3K pathway can mediate resistance to these agents, providing a strong rationale for combination therapy in melanoma. Here, a panel of nine low-passage human metastatic melanoma cell lines with BRAF mutations was tested in cell proliferation and protein expression assays for sensitivity to inhibitors of MEK (selumetinib) and BRAF (vemurafenib) as single agents and in combination with inhibitors of pan-PI3K (ZSTK474), pan-PI3K/mTOR (BEZ235), individual PI3K isoforms (p110alpha, A66; p110beta, TGX-221; p110gamma, AS-252424; p110delta, idelalisib), or mTORC1/2 (KU-0063794). Selumetinib and vemurafenib potently inhibited cell proliferation in all cell lines, especially in those that expressed low levels of phosphorylated AKT (pAKT). ZSTK474 and BEZ235 also inhibited cell proliferation in all cell lines and enhanced the antitumor activity of selumetinib and vemurafenib in the majority of lines by either interacting synergistically or additively to increase potency or by inducing cytotoxicity by significantly increasing the magnitude of cell growth inhibition. Furthermore, ZSTK474 or BEZ235 combined with selumetinib to produce robust inhibition of pERK, pAKT, and pS6 expression and synergistic inhibition of NZM20 tumor growth. The inhibitors of individual PI3K isoforms or mTORC1/2 were less effective at inhibiting cell proliferation either as single agents or in combination with selumetinib or vemurafenib, although KU-0063794 synergistically interacted with vemurafenib and increased the magnitude of cell growth inhibition with selumetinib or vemurafenib in certain cell lines. Overall, these results suggest that the sensitivity of BRAF-mutant melanoma cells to BRAF or MEK inhibitors is at least partly mediated by activation of the PI3K pathway and can be enhanced by combined inhibition of the BRAF/MEK and PI3K/mTOR signaling pathways. PMID- 26137450 TI - The Role of an Integrated Multidisciplinary Clinic in the Management of Patients with Cutaneous Lymphoma. AB - The clinical benefit of a multidisciplinary clinic practice model has been well described in a variety of medical specialties and cancer types. It proves particularly valuable when an integrated team is needed to optimally manage patients with rare or complex neoplasms. However, the ideal implementation of an integrated multidisciplinary care program for translational research and education has not been well reported. Herein, we propose how a multimodality cutaneous lymphoma (CL) clinic model can optimally manage CL patients. We offer our perspective on this model as an efficient means for delivering patient care, a continuing education resource for referring physicians, a conduit for translational and clinical research, and an educational tool for medical students, house staff, and fellows. PMID- 26137448 TI - Brain Tumor Immunotherapy: What have We Learned so Far? AB - High grade glioma is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy, and chemotherapy. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, we developed an immunotherapy schedule and we categorized patients into clinically defined risk profiles. We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients. The developmental program allows further improvements related to newest scientific insights. Finally, we developed a mode of care within academic centers to organize cell-based therapies for experimental clinical trials in a large number of patients. PMID- 26137451 TI - Patient perspectives on self-monitoring of blood glucose: perceived recommendations, behaviors and barriers in a clinic sample of adults with type 2 diabetes. AB - BACKGROUND: Patient-centered perspectives on self-monitoring of blood glucose (SBMG) were assessed in adults with type 2 diabetes using a self-regulation conceptual framework. METHODS: Participants (N = 589; 53 % female) were adults with type 2 diabetes who were recruited during routine appointments at a diabetes outpatient clinic in the Southeastern/lower Midwestern region of the United States. RESULTS: Participant's had varying perceptions regarding provider recommendations for SMBG (responder n = 380). Personal blood glucose testing patterns were also varied and reports frequently omitted (responder n = 296). Respondent's most frequent personal pattern was to test "occasionally, as needed," which did not differ by insulin use status, gender or age. In those not prescribed insulin, HbA1c reflected better control in those testing at least once per week (p = .040) or with a blood glucose goal (p = .018). 30.9 % endorsed at least monthly perceived encounters with SMBG barriers, with higher reports by women (p = .005) and younger (p = .006) participants. Poorer glycemic control was observed for participants with more frequently reported scheduling (p = .025, .041) and discouragement (p = .003) barriers. CONCLUSIONS: Findings suggest that many may experience difficulty integrating SMBG into their lives and are unsure of recommendations and appropriate function. Research is needed to promote best practice recommendations for SMBG. PMID- 26137453 TI - Ectrodactyly, Ectodermal Dysplasia, Cleft Lip, and Palate (EEC Syndrome) with Tetralogy of Fallot: A Very Rare Combination. AB - Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome (EEC) syndrome is a rare genetic disorder with an incidence of around 1 in 90,000 in population. It is known with various names including split hand-split foot-ectodermal dysplasia-cleft syndrome or split hand, cleft hand, or lobster claw hand/foot. We report first case of EEC with associated heart disease (Tetralogy of Fallot) who was diagnosed as EEC on the basis of clinical features and EEC was confirmed with genetic analysis. PMID- 26137452 TI - Neonatal Cholestasis - Differential Diagnoses, Current Diagnostic Procedures, and Treatment. AB - Cholestatic jaundice in early infancy is a complex diagnostic problem. Misdiagnosis of cholestasis as physiologic jaundice delays the identification of severe liver diseases. In the majority of infants, prolonged physiologic jaundice represent benign cases of breast milk jaundice, but few among them are masked and caused by neonatal cholestasis (NC) that requires a prompt diagnosis and treatment. Therefore, a prolonged neonatal jaundice, longer than 2 weeks after birth, must always be investigated because an early diagnosis is essential for appropriate management. To rapidly identify the cases with cholestatic jaundice, the conjugated bilirubin needs to be determined in any infant presenting with prolonged jaundice at 14 days of age with or without depigmented stool. Once NC is confirmed, a systematic approach is the key to reliably achieve the diagnosis in order to promptly initiate the specific, and in many cases, life-saving therapy. This strategy is most important to promptly identify and treat infants with biliary atresia, the most common cause of NC, as this requires a hepatoportoenterostomy as soon as possible. Here, we provide a detailed work-up approach including initial treatment recommendations and a clinically oriented overview of possible differential diagnoses in order to facilitate the early recognition and a timely diagnosis of cholestasis. This approach warrants a broad spectrum of diagnostic procedures and investigations including new methods that are described in this review. PMID- 26137454 TI - Does "Individual Placement and Support" Satisfy the Users' Needs? AB - This study aims to investigate clients' satisfaction with individual placement and support (IPS) at the University Hospital for Psychiatry Zurich (PUK). Furthermore, this study aims to investigate if clients feel the approach of IPS as a useful approach to fulfill their needs. One hundred twenty-five people were recruited from one of the three IPS services of PUK and were asked to complete a structured questionnaire. The following IPS services were available: (i) randomized controlled trial (RCT) ZHEPP (www.zhepp.ch), (ii) RCT ZInEP (www.zinep.ch), and (iii) us clinical supported employment service of PUK (IPS PUK). The clients mostly indicated that IPS was generally useful and fitted their needs. Overall satisfaction of the participants with the IPS services of the PUK was very high. Furthermore, client satisfaction and symptom severity are inversely associated. In conclusion, participants of the IPS services received the support they were looking for. This means that the approach of IPS fits the needs of different patient groups and can be used without any modifications. The most important limitation is the unequal group sizes. Therefore, the obtained results need to be strengthened by future research. PMID- 26137455 TI - From Neural and Social Cooperation to the Global Emergence of Cognition. AB - The recent article (Turalska et al., 2012) discusses the emergence of intelligence via criticality as a consequence of locality breakdown. Herein, we use criticality for the foundation of a novel generation of game theory making the local interaction between players yield long-range effects. We first establish that criticality is not confined to the Ising-like structure of the sociological model of (Turalska et al., 2012), called the decision making model (DMM), through the study of the emergence of altruism using the altruism selfishness model (ASM). Both models generate criticality, one by imitation of opinion (DMM) and the other by imitation of behavior (ASM). The dynamics of a sociological network ?? influences the behavioral network F through two game theoretic paradigms: (i) the value of altruism; (ii) the benefit of rapid consensus. In (i), the network ?? debates the moral issue of altruism by means of the DMM, while at the level F the individuals operate according to the ASM. The individuals of the level ??, through a weak influence on the individuals of the level F, exert a societal control on F, fitting the principle of complexity management and complexity matching. In (ii), the benefit to society is the rapid attainment of consensus in the ?? level. The agents of the level F operate according to the prisoner's dilemma prescription, with the defectors acting as DMM contrarians at the level ??. The contrarians, acting as the inhibitory links of neural networks, exert on society the same beneficial effect of maintaining the criticality-induced resilience that they generate in neural networks. The conflict between personal and social benefit makes the networks evolve toward criticality. Finally, we show that the theory of this article is compatible with recent discoveries in the burgeoning field of social neuroscience. PMID- 26137456 TI - Highly Thermostable Xylanase Production from A Thermophilic Geobacillus sp. Strain WSUCF1 Utilizing Lignocellulosic Biomass. AB - Efficient enzymatic hydrolysis of lignocellulose to fermentable sugars requires a complete repertoire of biomass deconstruction enzymes. Hemicellulases play an important role in hydrolyzing hemicellulose component of lignocellulose to xylooligosaccharides and xylose. Thermostable xylanases have been a focus of attention as industrially important enzymes due to their long shelf life at high temperatures. Geobacillus sp. strain WSUCF1 produced thermostable xylanase activity (crude xylanase cocktail) when grown on xylan or various inexpensive untreated and pretreated lignocellulosic biomasses such as prairie cord grass and corn stover. The optimum pH and temperature for the crude xylanase cocktail were 6.5 and 70 degrees C, respectively. The WSUCF1 crude xylanase was found to be highly thermostable with half-lives of 18 and 12 days at 60 and 70 degrees C, respectively. At 70 degrees C, rates of xylan hydrolysis were also found to be better with the WSUCF1 secretome than those with commercial enzymes, i.e., for WSUCF1 crude xylanase, Cellic-HTec2, and AccelleraseXY, the percent xylan conversions were 68.9, 49.4, and 28.92, respectively. To the best of our knowledge, WSUCF1 crude xylanase cocktail is among the most thermostable xylanases produced by thermophilic Geobacillus spp. and other thermophilic microbes (optimum growth temperature <=70 degrees C). High thermostability, activity over wide range of temperatures, and better xylan hydrolysis than commercial enzymes make WSUCF1 crude xylanase suitable for thermophilic lignocellulose bioconversion processes. PMID- 26137457 TI - Retroactivity in the Context of Modularly Structured Biomolecular Systems. AB - Synthetic biology has intensively promoted the technical implementation of modular strategies in the fabrication of biological devices. Modules are considered as networks of reactions. The behavior displayed by biomolecular systems results from the information processes carried out by the interconnection of the involved modules. However, in natural systems, module wiring is not a free of-charge process; as a consequence of interconnection, a reactive phenomenon called retroactivity emerges. This phenomenon is characterized by signals that propagate from downstream modules (the modules that receive the incoming signals upon interconnection) to upstream ones (the modules that send the signals upon interconnection). Such retroactivity signals, depending of their strength, may change and sometimes even disrupt the behavior of modular biomolecular systems. Thus, analysis of retroactivity effects in natural biological and biosynthetic systems is crucial to achieve a deeper understanding of how this interconnection between functionally characterized modules takes place and how it impacts the overall behavior of the involved cell. By discussing the modules interconnection in natural and synthetic biomolecular systems, we propose that such systems should be considered as quasi-modular. PMID- 26137458 TI - Design and Construction of a Whole Cell Bacterial 4-Hydroxyphenylacetic Acid and 2-Phenylacetic Acid Bioassay. AB - INTRODUCTION: Auxins are hormones that regulate plant growth and development. To accurately quantify the low levels of auxins present in plant and soil samples, sensitive detection methods are needed. In this study, the design and construction of two different whole cell auxin bioassays is illustrated. Both use the auxin responsive element HpaA as an input module but differ in output module. The first bioassay incorporates the gfp gene to produce a fluorescent bioassay. Whereas the second one utilizes the genes phzM and phzS to produce a pyocyanin producing bioassay whose product can be measured electrochemically. RESULTS: The fluorescent bioassay is able to detect 4-hydroxyphenylacetic acid (4-HPA) and 2 phenylacetic acid (PAA) concentrations from 60 MUM to 3 mM in a dose-responsive manner. The pyocyanin producing bioassay can detect 4-HPA concentrations from 1.9 to 15.625 MUM and PAA concentrations from 15.625 to 125 MUM, both in a dose responsive manner. CONCLUSION: A fluorescent whole cell auxin bioassay and an electrochemical whole cell auxin bioassay were constructed and tested. Both are able to detect 4-HPA and PAA at concentrations that are environmentally relevant to plant growth. PMID- 26137459 TI - Expression pattern of immediate early genes in the cerebellum of D1R KO, D2R KO, and wild type mice under vestibular-controlled activity. AB - We previously reported the different motor abilities of D1R knockout (KO), D2R KO and wild-type (WT) mice. To understand the interaction between the cerebellum and the striatal direct and indirect pathways, we examined the expression patterns of immediate early genes (IEG) in the cerebellum of these three genotypes of mice. In the WT naive mice, there was little IEG expression. However, we observed a robust expression of c-fos mRNA in the vermis and hemisphere after running rota rod tasks. In the vermis, c-fos was expressed throughout the lobules except lobule 7, and also in crus 1 of the ansiform lobule (Crus1), copula of the pyramis (Cop) and most significantly in the flocculus in the hemisphere. jun-B was much less expressed but more preferentially expressed in Purkinje cells. In addition, we observed significant levels of c-fos and jun-B expressions after handling mice, and after the stationary rota-rod task in naive mice. Surprisingly, we observed significant expression of c-fos and jun-B even 30 min after single weighing. Nonetheless, certain additional c-fos and jun-B expressions were observed in three genotypes of the mice that experienced several sessions of motor tasks 24 h after stationary rota-rod task and on days 1 and 5 after rota-rod tasks, but no significant differences in expressions after the running rota-rod tasks were observed among the three genotypes. In addition, there may be some differences 24 h after the stationary rota-rod task between the naive mice and the mice that experienced several sessions of motor tasks. PMID- 26137460 TI - BMI as a Predictor for Potential Difficult Tracheal Intubation in Males. AB - INTRODUCTION: Difficult tracheal intubation is a common source of mortality and morbidity in surgical and critical care settings. The incidence reported of difficult tracheal intubation is 0.1%-13% and reaches 14% in the obese population. The objective of our retrospective study was to investigate and compare the utility of body mass index (BMI) as indicator of difficult tracheal intubation in males and females. MATERIAL AND METHODS: We performed a retrospective chart review of patients who underwent abdominal surgeries with American Society of Anesthesiologists I to V under general anesthesia requiring endotracheal intubation. The following information was obtained from medical records for analysis: gender, age, height, weight, BMI, length of patient stay in the Post Anesthesia Care Unit, past medical history of sleep apnea, Mallampati score, and the American Society of Anesthesiologists classification assigned by the anesthesia care provider performing the endotracheal intubation. RESULTS: Of 4303 adult patients, 1970 (45.8%) men and 2333 (54.2%) women were enrolled in the study. Within this group, a total of 1673 (38.9%) patients were morbidly obese. The average age of the study group was 51.4 +/- 15.8 and the average BMI was 29.7 +/- 8.2 kg/m(2). The overall incidence of the encountered difficult intubations was 5.23% or 225 subjects. Thus, our results indicate that BMI is a reliable predictor of difficult tracheal intubation predominantly in the male population; another strong predictor, with a positive linear correlation, being the Mallampati score. CONCLUSION: In conclusion, our data shows that BMI is a reliable indicator of potential difficult tracheal intubation only in male surgical patients. PMID- 26137461 TI - Epigenetic Mechanisms Leading to Overexpression of HMGA Proteins in Human Pituitary Adenomas. AB - Overexpression of the high-mobility group A (HMGA)1 and HMGA2 proteins is a feature of all human pituitary adenoma (PAs) subtypes. However, amplification and/or rearrangement of the HMGA2 have been described in human prolactinomas, but rarely in other pituitary subtypes, and no genomic amplification of HMGA1 was detected in PAs. Here, we summarize the functional role of HMGA proteins in pituitary tumorigenesis and the epigenetic mechanisms contributing to HMGA overexpression in these tumors focusing on recent studies indicating a critical role of non-coding RNAs in modulating HMGA protein levels. PMID- 26137462 TI - Triple Therapy with Scopolamine, Ondansetron, and Dexamethasone for Prevention of Postoperative Nausea and Vomiting in Moderate to High-Risk Patients Undergoing Craniotomy Under General Anesthesia: A Pilot Study. AB - INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common complaints from patients and clinicians after a surgical procedure. According to the current Society of Ambulatory Anesthesia Consensus Guidelines, the general incidence of vomiting and nausea is around 30 and 50%, respectively; and up to 80% in high-risk patients. In previous studies, the reported incidence of PONV at 24 h after craniotomy was 43-70%. The transdermal scopolamine (TDS) delivery system contains a 1.5-mg drug reservoir, which is designed to deliver a continuous slow release of scopolamine through intact skin during the first 72 h of patch application. Therefore, we designed this single arm, non-randomized, pilot study to assess the efficacy and safety of triple therapy with scopolamine, ondansetron, and dexamethasone to prevent PONV. MATERIALS AND METHODS: In the preoperative area, subjects received an active TDS 1.5 mg that was applied to a hairless patch of skin in the mastoid area approximately 2 h prior to the operation. Immediately after anesthesia induction, all patients received a single 4 mg dose of ondansetron IV and a single 10 mg dose of dexamethasone IV. Patients who experienced nausea and/or vomiting received ondansetron 4 mg IV as the initial rescue medication. Postoperative nausea and vomiting assessments were performed for up to 120 h after surgery. RESULTS: A total of 36 subjects were analyzed. The overall incidence of PONV during the first 24 h after neurological surgery was 33% (n = 12). The incidence of nausea and emesis during the first 24 h after surgery was recorded as 33% (n = 12) and 16% (n = 6), respectively. CONCLUSION: Our data showed that this triple therapy regimen may be an efficient alternative regimen for PONV prophylaxis in patients undergoing neurological surgery with general anesthesia. Further studies using regimens affecting different receptor pathways should be performed to better prove the efficacy and safety in the prevention or delay of PONV. PMID- 26137463 TI - Acinar Cell Carcinoma of the Pancreas: Overview of Clinicopathologic Features and Insights into the Molecular Pathology. AB - Acinar cell carcinomas (ACCs) of the pancreas are rare pancreatic neoplasms accounting for about 1-2% of pancreatic tumors in adults and about 15% in pediatric subjects. They show different clinical symptoms at presentation, different morphological features, different outcomes, and different molecular alterations. This heterogeneous clinicopathological spectrum may give rise to difficulties in the clinical and pathological diagnosis with consequential therapeutic and prognostic implications. The molecular mechanisms involved in the onset and progression of ACCs are still not completely understood, although in recent years, several attempts have been made to clarify the molecular mechanisms involved in ACC biology. In this paper, we will review the main clinicopathological and molecular features of pancreatic ACCs of both adult and pediatric subjects to give the reader a comprehensive overview of this rare tumor type. PMID- 26137464 TI - How Long Do We Need to Follow-Up Our Hernia Patients to Find the Real Recurrence Rate? AB - INTRODUCTION: It is known that recurrences continue to occur after the follow-up period of 1-5 years usually used in most hernia studies. By reviewing the data in the Herniamed Hernia Registry documenting the time interval between the recurrent operation and previous inguinal hernia repair, the present study identifies the temporal course of onset of recurrence. PATIENTS AND METHODS: Prospective data were recorded in the Herniamed Registry between 1 September 2009 and 4 May 2015 on a total of 145,590 patients with 171,143 inguinal hernia operations. These included 18,774 operations due to an inguinal hernia recurrence (10.94%). During the same period, prospective data were collected on 24,385 incisional hernia operations. The latter cases included 5,328 patients with a recurrent incisional hernia (21.85%). RESULTS: Only 57.46% of all inguinal hernia recurrences occurred within 10 years of the previous inguinal hernia operation. Some of the remaining 42.54% of all recurrences occurred only much later, even after more than 50 years. The course of onset of recurrence is markedly different for incisional hernia. About 91.87% of such recurrences occur already within 10 years of the last operation. CONCLUSION: Ascertainment of the actual recurrence rate after hernia repair calls for a follow-up of 10 years for incisional hernia and of 50 years for inguinal hernia. The data collected can be used to give an approximate estimate with a shorter follow-up. PMID- 26137466 TI - Expression of Cathepsins B, D, and G in Infantile Hemangioma. AB - AIMS: The role of the renin-angiotensin system (RAS) in the biology of infantile hemangioma (IH) represents an emerging paradigm, particularly the involvement of renin, angiotensin converting enzyme, and angiotensin II. This study investigated the expression of cathepsins B, D, and G, enzymes that may modulate the RAS, in IH. MATERIALS AND METHODS: The expression of cathepsins B, D, and G was examined using immunohistochemistry, enzyme activity assays, mass spectrometry, and NanoString gene expression assay in IH samples at different phases of development. RESULTS: Immunohistochemical staining showed the expression of cathepsins B, D, and G in proliferating and involuted IH samples. This was confirmed at the transcriptional level using NanoString gene expression assays. Mass spectrometry confirmed the identification of cathepsins D and G in all three phases of IH development, whereas cathepsin B was detected in 2/2 proliferating and 1/2 involuting lesions. Enzyme activity assays demonstrated the activity of cathepsins B and D, but not G, in all phases of IH development. CONCLUSION: Our data demonstrated the presence of cathepsins B, D, and G in IH. Their role in modulating the RAS and the biology of IH offers potential novel targets for the management of this tumor. PMID- 26137465 TI - Emerging Applications of Bedside 3D Printing in Plastic Surgery. AB - Modern imaging techniques are an essential component of preoperative planning in plastic and reconstructive surgery. However, conventional modalities, including three-dimensional (3D) reconstructions, are limited by their representation on 2D workstations. 3D printing, also known as rapid prototyping or additive manufacturing, was once the province of industry to fabricate models from a computer-aided design (CAD) in a layer-by-layer manner. The early adopters in clinical practice have embraced the medical imaging-guided 3D-printed biomodels for their ability to provide tactile feedback and a superior appreciation of visuospatial relationship between anatomical structures. With increasing accessibility, investigators are able to convert standard imaging data into a CAD file using various 3D reconstruction softwares and ultimately fabricate 3D models using 3D printing techniques, such as stereolithography, multijet modeling, selective laser sintering, binder jet technique, and fused deposition modeling. However, many clinicians have questioned whether the cost-to-benefit ratio justifies its ongoing use. The cost and size of 3D printers have rapidly decreased over the past decade in parallel with the expiration of key 3D printing patents. Significant improvements in clinical imaging and user-friendly 3D software have permitted computer-aided 3D modeling of anatomical structures and implants without outsourcing in many cases. These developments offer immense potential for the application of 3D printing at the bedside for a variety of clinical applications. In this review, existing uses of 3D printing in plastic surgery practice spanning the spectrum from templates for facial transplantation surgery through to the formation of bespoke craniofacial implants to optimize post-operative esthetics are described. Furthermore, we discuss the potential of 3D printing to become an essential office-based tool in plastic surgery to assist in preoperative planning, developing intraoperative guidance tools, teaching patients and surgical trainees, and producing patient-specific prosthetics in everyday surgical practice. PMID- 26137467 TI - Photoreceptor engineering. AB - Sensory photoreceptors not only control diverse adaptive responses in Nature, but as light-regulated actuators they also provide the foundation for optogenetics, the non-invasive and spatiotemporally precise manipulation of cellular events by light. Novel photoreceptors have been engineered that establish control by light over manifold biological processes previously inaccessible to optogenetic intervention. Recently, photoreceptor engineering has witnessed a rapid development, and light-regulated actuators for the perturbation of a plethora of cellular events are now available. Here, we review fundamental principles of photoreceptors and light-regulated allostery. Photoreceptors dichotomize into associating receptors that alter their oligomeric state as part of light regulated allostery and non-associating receptors that do not. A survey of engineered photoreceptors pinpoints light-regulated association reactions and order-disorder transitions as particularly powerful and versatile design principles. Photochromic photoreceptors that are bidirectionally toggled by two light colors augur enhanced spatiotemporal resolution and use as photoactivatable fluorophores. By identifying desirable traits in engineered photoreceptors, we provide pointers for the design of future, light-regulated actuators. PMID- 26137469 TI - Improving Biomethane Production and Mass Bioconversion of Corn Stover Anaerobic Digestion by Adding NaOH Pretreatment and Trace Elements. AB - This research applied sodium hydroxide (NaOH) pretreatment and trace elements to improve biomethane production when using corn stover for anaerobic digestion. Full-factor experimental tests identified the best combination of trace elements with the NaOH pretreatment, indicating that the best combination was with 1.0, 0.4, and 0.4 mg.L(-1).d(-1) of elements Fe, Co, and Ni, respectively. The cumulative biomethane production adding NaOH pretreatment and trace elements was 11,367 mL; total solid bioconversion rate was 55.7%, which was 41.8%-62.2% higher than with NaOH-pretreatment alone and 22.2%-56.3% higher than with untreated corn stover. The best combination was obtained 5-9 days shorter than T90 and maintained good system operation stability. Only a fraction of the trace elements in the best combination was present in the resulting solution; more than 85% of the total amounts added were transferred into the solid fraction. Adding 0.897 g of Fe, 0.389 g of Co, and 0.349 g of Ni satisfied anaerobic digestion needs and enhanced biological activity at the beginning of the operation. The results showed that NaOH pretreatment and adding trace elements improve corn stover biodegradability and enhance biomethane production. PMID- 26137468 TI - MicroRNAs as potential target in human bone and soft tissue sarcoma therapeutics. AB - Sarcomas are highly aggressive heterogeneous tumors that are mesenchymal in origin. There have been vast advancements on identifying diagnostic markers for sarcomas including chromosomal translocations, but very little progress has been made to identify targeted therapies against them. The tumor heterogeneity, genetic complexity and the lack of drug studies make it challenging to recognize the potential targets and also accounts for the inadequate treatments in sarcomas. In recent years, microRNAs that are a part of small non-coding RNAs have shown promising results as potential diagnostic and prognostic biomarkers in multiple sarcoma types. This review focuses on the current knowledge of the microRNAs that are deregulated in sarcomas, and an insight on the strategies to target these microRNAs that are essential for developing improved therapies for various human sarcomas. PMID- 26137470 TI - Creating Well-Being: Increased Creativity and proNGF Decrease following Quadrato Motor Training. AB - Mind-body practices (MBP) are known to induce electrophysiological and morphological changes, whereas reports related to changes of neurotrophins are surprisingly scarce. Consequently, in the current paper, we focused on the Quadrato motor training (QMT), a newly developed whole-body movement-based MBP, which has been reported to enhance creativity. Here we report the effects of 4 weeks of daily QMT on creativity and proNGF level in two interrelated studies. In Study A, we examined the effects of QMT compared with a walking training (WT) in healthy adults, utilizing the alternate uses task. In contrast with the WT, QMT resulted in increased creativity. In addition, the change in creativity negatively correlated with the change in proNGF levels. In Study B, we examined QMT effects on creativity and additional metacognitive functions in children, using a nonintervention group as control. Similar to Study A, following QMT, we found a negative correlation of proNGF with creativity, as well as working memory updating and planning ability. Together, the current results point to the relationship between increased creativity and decreased proNGF following MBP. Thus, the current research emphasizes the importance of widening the scope of examination of "MBP in motion" in relation to metacognition and well-being. PMID- 26137472 TI - Production by Tobacco Transplastomic Plants of Recombinant Fungal and Bacterial Cell-Wall Degrading Enzymes to Be Used for Cellulosic Biomass Saccharification. AB - Biofuels from renewable plant biomass are gaining momentum due to climate change related to atmospheric CO2 increase. However, the production cost of enzymes required for cellulosic biomass saccharification is a major limiting step in this process. Low-cost production of large amounts of recombinant enzymes by transgenic plants was proposed as an alternative to the conventional microbial based fermentation. A number of studies have shown that chloroplast-based gene expression offers several advantages over nuclear transformation due to efficient transcription and translation systems and high copy number of the transgene. In this study, we expressed in tobacco chloroplasts microbial genes encoding five cellulases and a polygalacturonase. Leaf extracts containing the recombinant enzymes showed the ability to degrade various cell-wall components under different conditions, singly and in combinations. In addition, our group also tested a previously described thermostable xylanase in combination with a cellulase and a polygalacturonase to study the cumulative effect on the depolymerization of a complex plant substrate. Our results demonstrate the feasibility of using transplastomic tobacco leaf extracts to convert cell-wall polysaccharides into reducing sugars, fulfilling a major prerequisite of large scale availability of a variety of cell-wall degrading enzymes for biofuel industry. PMID- 26137471 TI - Stem Cells for Cutaneous Wound Healing. AB - Optimum healing of a cutaneous wound involves a well-orchestrated cascade of biological and molecular processes involving cell migration, proliferation, extracellular matrix deposition, and remodelling. When the normal biological process fails for any reason, this healing process can stall resulting in chronic wounds. Wounds are a growing clinical burden on healthcare systems and with an aging population as well as increasing incidences of obesity and diabetes, this problem is set to increase. Cell therapies may be the solution. A range of cell based approaches have begun to cross the rift from bench to bedside and the supporting data suggests that the appropriate administration of stem cells can accelerate wound healing. This review examines the main cell types explored for cutaneous wound healing with a focus on clinical use. The literature overwhelmingly suggests that cell therapies can help to heal cutaneous wounds when used appropriately but we are at risk of clinical use outpacing the evidence. There is a need, now more than ever, for standardised methods of cell characterisation and delivery, as well as randomised clinical trials. PMID- 26137473 TI - Association between AKT1 Gene Polymorphism rs2498794 and Smoking-Related Traits with reference to Cancer Susceptibility. AB - To clarify the potential role of variability within and around the AKT1 gene in smoking behaviors, we performed a single-nucleotide polymorphism (SNP) analysis of the AKT1 gene in an elderly Japanese cohort. Genotypes of the rs2498794 SNP, which is located in the fifth intron region of the AKT1 gene, were marginally but significantly associated with smoking duration in the total 999 samples of former and current smokers. Interestingly, this SNP had a marginally significant association with individual cancer history (past and current), especially in groups with a shorter smoking duration (<44 years) and fewer cigarettes per day (<=20). These data suggest that the rs2498794 polymorphism of the AKT1 gene is associated with a long smoking duration and may be involved in the predisposition to cancer when the smoking duration is short or the cigarettes per day is rate low. PMID- 26137474 TI - A Robust Supervised Variable Selection for Noisy High-Dimensional Data. AB - The Minimum Redundancy Maximum Relevance (MRMR) approach to supervised variable selection represents a successful methodology for dimensionality reduction, which is suitable for high-dimensional data observed in two or more different groups. Various available versions of the MRMR approach have been designed to search for variables with the largest relevance for a classification task while controlling for redundancy of the selected set of variables. However, usual relevance and redundancy criteria have the disadvantages of being too sensitive to the presence of outlying measurements and/or being inefficient. We propose a novel approach called Minimum Regularized Redundancy Maximum Robust Relevance (MRRMRR), suitable for noisy high-dimensional data observed in two groups. It combines principles of regularization and robust statistics. Particularly, redundancy is measured by a new regularized version of the coefficient of multiple correlation and relevance is measured by a highly robust correlation coefficient based on the least weighted squares regression with data-adaptive weights. We compare various dimensionality reduction methods on three real data sets. To investigate the influence of noise or outliers on the data, we perform the computations also for data artificially contaminated by severe noise of various forms. The experimental results confirm the robustness of the method with respect to outliers. PMID- 26137475 TI - Single Nucleotide Polymorphism (rs4932178) in the P1 Promoter of FURIN Is Not Prognostic to Colon Cancer. AB - High expression of the proprotein processing enzyme FURIN has been associated with tumor progression and metastasis. A SNP (rs4932178) in the promoter of FURIN has been reported to affect expression in liver, with the T allele resulting in higher expression than the C allele. In this study we have investigated the association of this SNP with prognostic and biological subgroups of colorectal cancer (CRC). In a panel of 1382 patients with CRC, this SNP had no impact on overall survival or on postoperative risk of relapse. This SNP also could not be linked with FURIN expression levels in CRC samples from the patients. Furthermore, we demonstrate in luciferase reporter experiments in the colon cancer cell lines Caco-2 and SW480 and in the hepatocellular carcinoma cell line Huh 7 that expression is not affected by the SNP. Since, FURIN inhibition in human colon cancer cell lines has previously been shown to repress tumor metastases, association between FURIN gene expression levels and postoperative relapse-free survival was also investigated. However, no association could be found. Altogether, we could not confirm an effect of the SNP on FURIN expression in vitro and no correlations could be found in vivo with FURIN expression or outcome. PMID- 26137476 TI - Enzymatic Saccharification of Lignocellulosic Residues by Cellulases Obtained from Solid State Fermentation Using Trichoderma viride. AB - The aim of this study was to verify the viability of lignocellulosic substrates to obtain renewable energy source, through characterization of the cellulolytic complex, which was obtained by solid state fermentation using Trichoderma viride. Enzymatic activity of the cellulosic complex was measured during saccharification of substrates filter paper, eucalyptus sawdust, and corncob, and compared with the activity of commercial cellulase. The characterization of the enzymes was performed by a 2(2) Full Factorial Design, where the pH and temperature were the variables of study. Enzymatic saccharification of different substrates appearedviable until 12 to be viable until 12 h; after this period the activity decreased for both enzymatic forms (cellulolytic complex and commercial cellulase). The enzymatic activity of the commercial cellulase was favored with the use of corncob as substrate, while the cellulolytic complex does not show any difference in its specificity by the substrates studied. The largest activities of both enzymes were obtained in the temperature and pH range between 40 degrees C and 50 degrees C and 4.8 and 5.2, respectively. The cellulolytic complex obtained appeared to be viable for the saccharification of lignocellulosic residues compared with the commercial cellulase. PMID- 26137477 TI - Cytogenomic Evaluation of Subjects with Syndromic and Nonsyndromic Conotruncal Heart Defects. AB - Despite considerable advances in the detection of genomic abnormalities in congenital heart disease (CHD), the etiology of CHD remains largely unknown. CHD is the most common birth defect and is a major cause of infant morbidity and mortality, and conotruncal defects constitute 20% of all CHD cases. We used array comparative genomic hybridization (array-CGH) to retrospectively study 60 subjects with conotruncal defects and identify genomic imbalances. The DNA copy number variations (CNVs) detected were matched with data from genomic databases, and their clinical significance was evaluated. We found that 38.3% (23/60) of CHD cases possessed genomic imbalances. In 8.3% (5/60) of these cases, the imbalances were causal or potentially causal CNVs; in 8.3% (5/60), unclassified CNVs were identified; and in 21.6% (13/60), common variants were detected. Although the interpretation of the results must be refined and there is not yet a consensus regarding the types of CHD cases in which array-CGH should be used as a first line test, the identification of these CNVs can assist in the evaluation and management of CHD. The results of such studies emphasize the growing importance of the use of genome-wide assays in subjects with CHD to increase the number of genomic data sets associated with this condition. PMID- 26137478 TI - DNAseq Workflow in a Diagnostic Context and an Example of a User Friendly Implementation. AB - Over recent years next generation sequencing (NGS) technologies evolved from costly tools used by very few, to a much more accessible and economically viable technology. Through this recently gained popularity, its use-cases expanded from research environments into clinical settings. But the technical know-how and infrastructure required to analyze the data remain an obstacle for a wider adoption of this technology, especially in smaller laboratories. We present GensearchNGS, a commercial DNAseq software suite distributed by Phenosystems SA. The focus of GensearchNGS is the optimal usage of already existing infrastructure, while keeping its use simple. This is achieved through the integration of existing tools in a comprehensive software environment, as well as custom algorithms developed with the restrictions of limited infrastructures in mind. This includes the possibility to connect multiple computers to speed up computing intensive parts of the analysis such as sequence alignments. We present a typical DNAseq workflow for NGS data analysis and the approach GensearchNGS takes to implement it. The presented workflow goes from raw data quality control to the final variant report. This includes features such as gene panels and the integration of online databases, like Ensembl for annotations or Cafe Variome for variant sharing. PMID- 26137479 TI - Neurophysiological Effects of Meditation Based on Evoked and Event Related Potential Recordings. AB - Evoked potentials (EPs) are a relatively noninvasive method to assess the integrity of sensory pathways. As the neural generators for most of the components are relatively well worked out, EPs have been used to understand the changes occurring during meditation. Event-related potentials (ERPs) yield useful information about the response to tasks, usually assessing attention. A brief review of the literature yielded eleven studies on EPs and seventeen on ERPs from 1978 to 2014. The EP studies covered short, mid, and long latency EPs, using both auditory and visual modalities. ERP studies reported the effects of meditation on tasks such as the auditory oddball paradigm, the attentional blink task, mismatched negativity, and affective picture viewing among others. Both EP and ERPs were recorded in several meditations detailed in the review. Maximum changes occurred in mid latency (auditory) EPs suggesting that maximum changes occur in the corresponding neural generators in the thalamus, thalamic radiations, and primary auditory cortical areas. ERP studies showed meditation can increase attention and enhance efficiency of brain resource allocation with greater emotional control. PMID- 26137481 TI - Percutaneous Dorsal Instrumentation of Vertebral Burst Fractures: Value of Additional Percutaneous Intravertebral Reposition-Cadaver Study. AB - PURPOSE: The treatment of vertebral burst fractures is still controversial. The aim of the study is to evaluate the purpose of additional percutaneous intravertebral reduction when combined with dorsal instrumentation. METHODS: In this biomechanical cadaver study twenty-eight spine segments (T11-L3) were used (male donors, mean age 64.9 +/- 6.5 years). Burst fractures of L1 were generated using a standardised protocol. After fracture all spines were allocated to four similar groups and randomised according to surgical techniques (posterior instrumentation; posterior instrumentation + intravertebral reduction device + cement augmentation; posterior instrumentation + intravertebral reduction device without cement; and intravertebral reduction device + cement augmentation). After treatment, 100000 cycles (100-600 N, 3 Hz) were applied using a servohydraulic loading frame. RESULTS: Overall anatomical restoration was better in all groups where the intravertebral reduction device was used (p < 0.05). In particular, it was possible to restore central endplates (p > 0.05). All techniques decreased narrowing of the spinal canal. After loading, clearance could be maintained in all groups fitted with the intravertebral reduction device. Narrowing increased in the group treated with dorsal instrumentation. CONCLUSIONS: For height and anatomical restoration, the combination of an intravertebral reduction device with dorsal instrumentation showed significantly better results than sole dorsal instrumentation. PMID- 26137482 TI - Nanofibrillated Cellulose and Copper Nanoparticles Embedded in Polyvinyl Alcohol Films for Antimicrobial Applications. AB - Our long-term goal is to develop a hybrid cellulose-copper nanoparticle material as a functional nanofiller to be incorporated in thermoplastic resins for efficiently improving their antimicrobial properties. In this study, copper nanoparticles were first synthesized through chemical reduction of cupric ions on TEMPO nanofibrillated cellulose (TNFC) template using borohydride as a copper reducing agent. The resulting hybrid material was embedded into a polyvinyl alcohol (PVA) matrix using a solvent casting method. The morphology of TNFC copper nanoparticles was analyzed by transmission electron microscopy (TEM); spherical copper nanoparticles with average size of 9.2 +/- 2.0 nm were determined. Thermogravimetric analysis and antimicrobial performance of the films were evaluated. Slight variations in thermal properties between the nanocomposite films and PVA resin were observed. Antimicrobial analysis demonstrated that one week exposure of nonpathogenic Escherichia coli DH5alpha to the nanocomposite films results in up to 5-log microbial reduction. PMID- 26137480 TI - Paclitaxel and Its Evolving Role in the Management of Ovarian Cancer. AB - Paclitaxel, a class of taxane with microtubule stabilising ability, has remained with platinum based therapy, the standard care for primary ovarian cancer management. A deeper understanding of the immunological basis and other potential mechanisms of action together with new dosing schedules and/or routes of administration may potentiate its clinical benefit. Newer forms of taxanes, with better safety profiles and higher intratumoural cytotoxicity, have yet to demonstrate clinical superiority over the parent compound. PMID- 26137483 TI - Three-Dimensional Analysis of the Characteristics of the Femoral Canal Isthmus: An Anatomical Study. AB - PURPOSE: To establish a new approach for measuring and locating the femoral intramedullary canal isthmus in 3-dimensional (3D) space. METHODS: Based on the computed tomography data from 204 Chinese patients, 3D models of the whole femur and the corresponding femoral isthmus tube were reconstructed using Mimics software (Materialise, Haasrode, Belgium). The anatomical parameters of the femur and the isthmus, including the femur length and radius, and the isthmus diameter and height, were measured accordingly. RESULTS: The mean ratio of the isthmus height versus the femoral height was 55 +/- 4.8%. The mean diameter of the isthmus was 10.49 +/- 1.52 mm. The femoral length, the isthmus diameter, and the isthmus tube length were significantly larger in the male group. Significant correlations were observed between the femoral length and the isthmus diameter (r = 0.24, p < 0.01) and between the femoral length and the isthmus height (r = 0.6, p < 0.01). Stepwise linear regression analyses demonstrated that the femoral length and radius were the most important factors influencing the location and dimension of the femoral canal isthmus. CONCLUSION: The current study developed a new approach for measuring the femoral canal and for optimization of customer specific femoral implants. PMID- 26137484 TI - An Exploratory Analysis of the Relationship between Cardiometabolic Risk Factors and Cognitive/Academic Performance among Adolescents. AB - This exploratory study examines the relationship between cardiometabolic risk factors (blood pressure, waist circumference, BMI, and total cholesterol) and cognitive/academic performance. In this study, 1297 Taiwanese tenth-grade volunteers are recruited. Scores from the Basic Competency Test, an annual national competitive entrance examination, are used to evaluate academic performance. Cognitive abilities are accessed via the Multiple Aptitude Test Battery. The results indicate that systolic blood pressure is significantly, negatively associated with academic performance, both in male and female subjects. BMI and waist circumference are associated with verbal reasoning performance with an inverse U-shaped pattern, suggesting that both low and high BMI/waist circumference may be associated with lower verbal reasoning performance. PMID- 26137485 TI - Qigong as a Traditional Vegetative Biofeedback Therapy: Long-Term Conditioning of Physiological Mind-Body Effects. AB - A contemporary understanding of Chinese Medicine (CM) regards CM diagnosis as a functional vegetative state that may be treated by vegetative reflex therapies such as acupuncture. Within this context, traditional mind-body exercises such as Qigong can be understood as an attempt to enhance physiological proprioception, by combining a special state of "awareness" with posture, movement, and breath control. We have formerly trained young auditing flutists in "White Ball" Qigong to minimize anxiety-induced cold hands and lower anxiety-induced heart rate. Functional changes occurred 2-5 min after training and were observed over the whole training program, allowing the children to control their symptoms. In our current work, we report that warm fingers and calm hearts could be induced by the children even without Qigong exercises. Thus, these positive changes once induced and "conditioned" vegetatively were stable after weeks of training. This may show the mechanism by which Qigong acts as a therapeutic measure in disease: positive vegetative pathways may be activated instead of dysfunctional functional patterns. The positive vegetative patterns then may be available in critical stressful situations. Qigong exercise programs may therefore be understood as an ancient vegetative biofeedback exercise inducing positive vegetative functions which are added to the individual reactive repertoire. PMID- 26137486 TI - Validation and Test-Retest Reliability of New Thermographic Technique Called Thermovision Technique of Dry Needling for Gluteus Minimus Trigger Points in Sciatica Subjects and TrPs-Negative Healthy Volunteers. AB - The aim of this study was to assess the validity and test-retest reliability of Thermovision Technique of Dry Needling (TTDN) for the gluteus minimus muscle. TTDN is a new thermography approach used to support trigger points (TrPs) diagnostic criteria by presence of short-term vasomotor reactions occurring in the area where TrPs refer pain. Method. Thirty chronic sciatica patients (n=15 TrP-positive and n=15 TrPs-negative) and 15 healthy volunteers were evaluated by TTDN three times during two consecutive days based on TrPs of the gluteus minimus muscle confirmed additionally by referred pain presence. TTDN employs average temperature (T avr), maximum temperature (T max), low/high isothermal-area, and autonomic referred pain phenomenon (AURP) that reflects vasodilatation/vasoconstriction. Validity and test-retest reliability were assessed concurrently. Results. Two components of TTDN validity and reliability, T avr and AURP, had almost perfect agreement according to kappa (e.g., thigh: 0.880 and 0.938; calf: 0.902 and 0.956, resp.). The sensitivity for T avr, T max, AURP, and high isothermal-area was 100% for everyone, but specificity of 100% was for T avr and AURP only. Conclusion. TTDN is a valid and reliable method for T avr and AURP measurement to support TrPs diagnostic criteria for the gluteus minimus muscle when digitally evoked referred pain pattern is present. PMID- 26137488 TI - Toward a Literature-Driven Definition of Big Data in Healthcare. AB - OBJECTIVE: The aim of this study was to provide a definition of big data in healthcare. METHODS: A systematic search of PubMed literature published until May 9, 2014, was conducted. We noted the number of statistical individuals (n) and the number of variables (p) for all papers describing a dataset. These papers were classified into fields of study. Characteristics attributed to big data by authors were also considered. Based on this analysis, a definition of big data was proposed. RESULTS: A total of 196 papers were included. Big data can be defined as datasets with Log(n*p) >= 7. Properties of big data are its great variety and high velocity. Big data raises challenges on veracity, on all aspects of the workflow, on extracting meaningful information, and on sharing information. Big data requires new computational methods that optimize data management. Related concepts are data reuse, false knowledge discovery, and privacy issues. CONCLUSION: Big data is defined by volume. Big data should not be confused with data reuse: data can be big without being reused for another purpose, for example, in omics. Inversely, data can be reused without being necessarily big, for example, secondary use of Electronic Medical Records (EMR) data. PMID- 26137487 TI - Drug Delivery Innovations for Enhancing the Anticancer Potential of Vitamin E Isoforms and Their Derivatives. AB - Vitamin E isoforms have been extensively studied for their anticancer properties. Novel drug delivery systems (DDS) that include liposomes, nanoparticles, and micelles are actively being developed to improve Vitamin E delivery. Furthermore, several drug delivery systems that incorporate Vitamin E isoforms have been synthesized in order to increase the bioavailability of chemotherapeutic agents or to provide a synergistic effect. D-alpha-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) is a synthetic derivative of natural alpha tocopherol which is gaining increasing interest in the development of drug delivery systems and has also shown promising anticancer effect as a single agent. This review provides a summary of the properties and anticancer effects of the most potent Vitamin E isoforms and an overview of the various formulations developed to improve their efficacy, with an emphasis on the use of TPGS in drug delivery approaches. PMID- 26137489 TI - Mean Expected Error in Prediction of Total Body Water: A True Accuracy Comparison between Bioimpedance Spectroscopy and Single Frequency Regression Equations. AB - For several decades electrical bioimpedance (EBI) has been used to assess body fluid distribution and body composition. Despite the development of several different approaches for assessing total body water (TBW), it remains uncertain whether bioimpedance spectroscopic (BIS) approaches are more accurate than single frequency regression equations. The main objective of this study was to answer this question by calculating the expected accuracy of a single measurement for different EBI methods. The results of this study showed that all methods produced similarly high correlation and concordance coefficients, indicating good accuracy as a method. Even the limits of agreement produced from the Bland-Altman analysis indicated that the performance of single frequency, Sun's prediction equations, at population level was close to the performance of both BIS methods; however, when comparing the Mean Absolute Percentage Error value between the single frequency prediction equations and the BIS methods, a significant difference was obtained, indicating slightly better accuracy for the BIS methods. Despite the higher accuracy of BIS methods over 50 kHz prediction equations at both population and individual level, the magnitude of the improvement was small. Such slight improvement in accuracy of BIS methods is suggested insufficient to warrant their clinical use where the most accurate predictions of TBW are required, for example, when assessing over-fluidic status on dialysis. To reach expected errors below 4-5%, novel and individualized approaches must be developed to improve the accuracy of bioimpedance-based methods for the advent of innovative personalized health monitoring applications. PMID- 26137490 TI - Mindful Emotion Regulation: Exploring the Neurocognitive Mechanisms behind Mindfulness. AB - The purpose of this paper is to review some of the psychological and neural mechanisms behind mindfulness practice in order to explore the unique factors that account for its positive impact on emotional regulation and health. After reviewing the mechanisms of mindfulness and its effects on clinical populations we will consider how the practice of mindfulness contributes to the regulation of emotions. We argue that mindfulness has achieved effective outcomes in the treatment of anxiety, depression, and other psychopathologies through the contribution of mindfulness to emotional regulation. We consider the unique factors that mindfulness meditation brings to the process of emotion regulation that may account for its effectiveness. We review experimental evidence that points towards the unique effects of mindfulness specifically operating over and above the regulatory effects of cognitive reappraisal mechanisms. A neuroanatomical circuit that leads to mindful emotion regulation is also suggested. This paper thereby aims to contribute to proposed models of mindfulness for research and theory building by proposing a specific model for the unique psychological and neural processes involved in mindful detachment that account for the effects of mindfulness over and above the effects accounted for by other well-established emotional regulation processes such as cognitive reappraisal. PMID- 26137491 TI - The Effects of Guided Imagery on Heart Rate Variability in Simulated Spaceflight Emergency Tasks Performers. AB - OBJECTIVES: The present study aimed to investigate the effects of guided imagery training on heart rate variability in individuals while performing spaceflight emergency tasks. MATERIALS AND METHODS: Twenty-one student subjects were recruited for the experiment and randomly divided into two groups: imagery group (n = 11) and control group (n = 10). The imagery group received instructor-guided imagery (session 1) and self-guided imagery training (session 2) consecutively, while the control group only received conventional training. Electrocardiograms of the subjects were recorded during their performance of nine spaceflight emergency tasks after imagery training. RESULTS: In both of the sessions, the root mean square of successive differences (RMSSD), the standard deviation of all normal NN (SDNN), the proportion of NN50 divided by the total number of NNs (PNN50), the very low frequency (VLF), the low frequency (LF), the high frequency (HF), and the total power (TP) in the imagery group were significantly higher than those in the control group. Moreover, LF/HF of the subjects after instructor guided imagery training was lower than that after self-guided imagery training. CONCLUSIONS: Guided imagery was an effective regulator for HRV indices and could be a potential stress countermeasure in performing spaceflight tasks. PMID- 26137492 TI - Precision Medicine for Continuing Phenotype Expansion of Human Genetic Diseases. AB - Determining the exact genetic causes for a patient and providing definite molecular diagnoses are core elements of precision medicine. Individualized patient care is often limited by our current knowledge of disease etiologies and commonly used phenotypic-based diagnostic approach. The broad and incompletely understood phenotypic spectrum of a disease and various underlying genetic heterogeneity also present extra challenges to our clinical practice. With the rapid adaptation of new sequence technology in clinical setting for diagnostic purpose, phenotypic expansions of disease spectrum are becoming increasingly common. Understanding the underlying molecular mechanisms will help us to integrate genomic information into the workup of individualized patient care and make better clinical decisions. PMID- 26137493 TI - Isolation and Characterization of Human Lung Lymphatic Endothelial Cells. AB - Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID- 26137494 TI - Promoting Effects on Proliferation and Chondrogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells by Four "Kidney-Tonifying" Traditional Chinese Herbs. AB - Traditional Chinese medicine can promote the proliferation of bone marrow-derived mesenchymal stem cells (BMSCs). We chose four "Kidney-tonifying" Chinese herbal medicines, Radix Astragali, Salvia, Herba Epimedii, and Saussurea Involucrata, to evaluate whether they had positive effects on the proliferation of BMSCs and TGF beta1-induced chondrogenic differentiation of BMSCs. The four Chinese herbal medicines were intragastrically administered to Sprague-Dawley rats, respectively, to prepare drug-containing serums of corresponding Chinese herbs. BMSCs were isolated, cultured, and exposed to culture solution containing 1%, 5%, 10%, and 15% (v/v) Radix Astragali-, Salvia-, Herba Epimedii-, and Saussurea Involucrata-containing serum, respectively. TGF-beta1-induced BMSCs were addressed in the same manner. Collagen type II protein was assessed by immunofluorescence methods. To assess whether the drug-containing serums had positive effects on the proliferation of BMSCs and TGF-beta1-induced BMSCs, MTT method was assessed. The proliferation of BMSCs was significantly enhanced when exposed to culture solutions containing 1% and 5% Radix Astragali-, 1% and 5% Salvia-, 5% Herba Epimedii-, and 1%, 5%, and 10% Saussurea Involucrata-containing serum. The proliferation of TGF-beta1-induced BMSCs was significantly enhanced when exposed to 1%, 5%, and 15% Radix Astragali-, 10% and 15% Salvia-, 5%, and 15% Herba Epimedii-, and 1%, 5%, and 10% Saussurea Involucrata-containing serum. PMID- 26137495 TI - Measuring a Journey without Goal: Meditation, Spirituality, and Physiology. AB - The secular practice of meditation is associated with a range of physiological and cognitive effects, including lower blood pressure, lower cortisol, cortical thickening, and activation of areas of the brain associated with attention and emotion regulation. However, in the context of spiritual practice, these benefits are secondary gains, as the primary aim is spiritual transformation. Despite obvious difficulties in trying to measure a journey without goal, spiritual aspects involved in the practice of meditation should also be addressed by experimental study. This review starts by considering meditation in the form of the relaxation response (a counterpart to the stress response), before contrasting mindfulness research that emphasizes the role of attention and alertness in meditation. This contrast demonstrates how reference to traditional spiritual texts (in this case Buddhist) can be used to guide research questions involving meditation. Further considerations are detailed, along with the proposal that research should triangulate spiritual textual sources, first person accounts (i.e., neurophenomenology), and physiological/cognitive measures in order to aid our understanding of meditation, not only in the secular context of health benefits, but also in the context of spiritual practice. PMID- 26137496 TI - Mindfulness Meditation Improves Mood, Quality of Life, and Attention in Adults with Attention Deficit Hyperactivity Disorder. AB - OBJECTIVE: Adults with attention deficit hyperactivity disorder (ADHD) display affective problems and impaired attention. Mood in ADHD can be improved by mindful awareness practices (MAP), but results are mixed regarding the enhancement of attentional performance. Here we evaluated MAP-induced changes in quality of life (QoL), mood, and attention in adult ADHD patients and controls using more measures of attention than prior studies. METHODS: Twenty-one ADHD patients and 8 healthy controls underwent 8 weekly MAP sessions; 22 similar patients and 9 controls did not undergo the intervention. Mood and QoL were assessed using validated questionnaires, and attention was evaluated using the Attentional Network Test (ANT) and the Conners Continuous Performance Test (CPT II), before and after intervention. RESULTS: MAP enhanced sustained attention (ANT) and detectability (CPT II) and improved mood and QoL of patients and controls. CONCLUSION: MAP is a complementary intervention that improves affect and attention of adults with ADHD and controls. PMID- 26137498 TI - Inhibition of TNF-alpha Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy. AB - We hypothesised that tumour necrosis factor-alpha (TNF-alpha) may enhance receptor activator of nuclear factor-kappabeta ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-alpha (anti-TNF-alpha). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-alpha resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF alpha modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID- 26137499 TI - Generating Isogenic Deletions (Knockouts) in Francisella tularensis, a Highly infectious and Fastidious Gram-negative Bacterium. AB - Generating bacterial gene deletion mutants, also known as knockouts (KOs), is a powerful tool to investigate individual gene functions. However, fastidious bacteria such as Francisella tularensis (F. tularensis) often are difficult to genetically manipulate. Indeed, many different approaches have been tested to generate F. tularensis mutants. First, Tn5-based EZ::TN transposons have been successfully used to generate transposon libraries in F. tularensis (Qin and Mann, 2006; Weiss et al., 2007). However, creating a comprehensive transposon library with saturating mutations can be laborious, screening for gene disruption requires high-throughput assays where known phenotypes can be measured, and transposons may not completely inactivate the gene of interest or may alter downstream gene expression. Second, group II introns (also referred to as Targetron) have been used to inactivate F. tularensis genes of interest (Rodriguez et al., 2008; Rodriguez et al., 2009). Targetron functions by forming a complex between plasmid-encoded RNA and chromosomal DNA, followed by group II intron insertion into the gene of interest. The main advantage of Targetron is that it does not require an antibiotic resistance marker. However, as noted for transposons, targetron gene insertions may not eliminate all gene functions or may affect downstream gene expression. Third, homologous recombination can be used to completely replace the chromosomal target gene with a selectable marker, such as an antibiotic resistance marker. This classical genetic technique has been used in many F. tularensis studies (Ramakrishnan et al., 2008; Ren et al., 2014; Mohapatra et al., 2008; Robertson et al., 2013). To accomplish this, a suicide plasmid is engineered to include a selectable marker flanked by regions upstream and downstream of the gene of interest. This KO plasmid can be delivered into host bacteria by many methods, including electroporation, chemical transformation, or conjugation. Here, we describe an optimized procedure to generate KO plasmid constructs, use E. coli to conjugatively transfer the plasmid into F. tularensis, select for F. tularensis KOs using a series of kanamycin-, hygromycin-, and sucrose-resistance steps, and confirm that the gene of interest has been deleted (general overview of the knockout protocol diagramed in Figure 1). This optimized procedure is relatively simple, rapid, and, more importantly, includes a series of both positive and negative selection steps to increase the chances of deleting a target gene from F. tularensis. PMID- 26137497 TI - Diabetic Retinopathy: Vascular and Inflammatory Disease. AB - Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted. PMID- 26137501 TI - EBioMedicine: Bridging Two Cultures to Improve Health. PMID- 26137502 TI - Ebola Conquers West Africa - More to Come? PMID- 26137503 TI - HIV Prevention and Treatment Fields Join Forces. PMID- 26137500 TI - Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs. AB - Cancer stem cells (CSCs) or cancer initiating cells (CICs) maintain self-renewal and multilineage differentiation properties of various tumors, as well as the cellular heterogeneity consisting of several subpopulations within tumors. CSCs display the malignant phenotype, self-renewal ability, altered genomic stability, specific epigenetic signature, and most of the time can be phenotyped by cell surface markers (e.g., CD133, CD24, and CD44). Numerous studies support the concept that non-stem cancer cells (non-CSCs) are sensitive to cancer therapy while CSCs are relatively resistant to treatment. In glioblastoma stem cells (GSCs), there is clonal heterogeneity at the genetic level with distinct tumorigenic potential, and defined GSC marker expression resulting from clonal evolution which is likely to influence disease progression and response to treatment. Another level of complexity in glioblastoma multiforme (GBM) tumors is the dynamic equilibrium between GSCs and differentiated non-GSCs, and the potential for non-GSCs to revert (dedifferentiate) to GSCs due to epigenetic alteration which confers phenotypic plasticity to the tumor cell population. Moreover, exposure of the differentiated GBM cells to therapeutic doses of temozolomide (TMZ) or ionizing radiation (IR) increases the GSC pool both in vitro and in vivo. This review describes various subtypes of GBM, discusses the evolution of CSC models and epigenetic plasticity, as well as interconversion between GSCs and differentiated non-GSCs, and offers strategies to potentially eliminate GSCs. PMID- 26137504 TI - Malaria Vaccines: Progressing on a Bumpy Road. PMID- 26137505 TI - alpha(+)Thalassemia Antagonizes the Malaria-protective Effects of Sickle-Cell Trait. PMID- 26137506 TI - Assessing Cellular Responses in Sepsis. PMID- 26137507 TI - Development of a Tissue-Engineering Vascular Graft for Use in Congenital Heart Surgery. PMID- 26137508 TI - Induction of Heat Shock Proteins in the Therapy of Type 2 Diabetes and Metabolic Syndrome. PMID- 26137509 TI - In Vivo Application of Tissue-Engineered Veins Using Autologous Peripheral Whole Blood: A Proof of Concept Study. AB - Vascular diseases are increasing health problems affecting > 25 million individuals in westernized societies. Such patients could benefit from transplantation of tissue-engineered vascular grafts using autologous cells. One challenge that has limited this development is the need for cell isolation, and risks associated with ex vivo expanded stem cells. Here we demonstrate a novel approach to generate transplantable vascular grafts using decellularized allogeneic vascular scaffolds, repopulated with peripheral whole blood (PWB) in vitro in a bioreactor. Circulating, VEGFR-2 +/CD45 + and a smaller fraction of VEGFR-2 +/CD14 + cells contributed to repopulation of the graft. SEM micrographs showed flat cells on the luminal surface of the grafts consistent with endothelial cells. For clinical validation, two autologous PWB tissue-engineered vein conduits were prepared and successfully used for by-pass procedures in two pediatric patients. These results provide a proof of principle for the generation of transplantable vascular grafts using a simple autologous blood sample, making it clinically feasible globally. PMID- 26137511 TI - 2014: A Year of Breakthroughs for Translational Science. PMID- 26137510 TI - Mild Electrical Stimulation with Heat Shock Reduces Visceral Adiposity and Improves Metabolic Abnormalities in Subjects with Metabolic Syndrome or Type 2 Diabetes: Randomized Crossover Trials. AB - BACKGROUND: The induction of heat shock protein (HSP) 72 by mild electrical stimulation with heat shock (MES + HS), which improves visceral adiposity and insulin resistance in mice, may be beneficial in treating metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM). METHODS: Using open-label crossover trials, 40 subjects with MS or T2DM were randomly assigned using computer-generated random numbers to 12 weeks of therapeutic MES + HS followed by 12 weeks of no treatment, or vice versa. During the intervention period, physical and biochemical markers were measured. FINDINGS: Compared to no treatment, MES + HS treatment was associated with a significant decrease in visceral adiposity (- 7.54 cm(2) (- 8.61%), 95% CI - 8.55 to - 6.53 (p = 0.037) in MS, - 19.73 cm(2) (- 10.89%), 95% CI - 20.97 to - 18.49 (p = 0.003) in T2DM). Fasting plasma glucose levels were decreased by 3.74 mg/dL (- 5.28%: 95% CI - 4.37 to - 3.09 mg/dL, p = 0.029) in MS and by 14.97 mg/dL (10.40%: 95% CI - 15.79 to 14.15 mg/dL, p < 0.001) in T2DM, and insulin levels were also reduced by 10.39% and 25.93%, respectively. HbA1c levels showed a trend toward reduction (- 0.06%) in MS, and was significantly declined by - 0.43% (95% CI - 0.55 to - 0.31%, p = 0.009) in T2DM. HbA1c level of less than 7.0% was achieved in 52.5% of the MES + HS-treated T2DM patients in contrast to 15% of the non-treated period. Several insulin resistance indices, inflammatory cytokines or adipokines, including C-reactive protein, adiponectin, and tumor necrosis factor-alpha, were all improved in both groups. In isolated monocytes, HSP72 expression was increased and cytokine expression was reduced following MES + HS treatment. Glucose excursions on meal tolerance test were lower after using MES + HS in T2DM. INTERPRETATION: This combination therapy has beneficial impacts on body composition, metabolic abnormalities, and inflammation in subjects with MS or T2DM. Activation of the heat shock response by MES + HS may provide a novel approach for the treatment of lifestyle-related diseases. FUNDING: Funding for this research was provided by MEXT KAKENHI (Grants-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology, Japan). PMID- 26137512 TI - Stem Cell-Derived Beta Cells for Treatment of Type 1 Diabetes? PMID- 26137513 TI - Key Challenges in Rheumatic and Musculoskeletal Disease Translational Research. PMID- 26137514 TI - Dangerous Membranes: Viruses That Subvert Autophagosomes. PMID- 26137515 TI - Biomarkers of HIV Susceptibility and Disease Progression. PMID- 26137516 TI - Nanoparticle Formulations of siRNA: The Next Generation of Targeted Therapy for Lymphomas and Leukemias? PMID- 26137517 TI - Expression Profiles and Clinicopathologic Features in Early Resected Non-small cell Lung Cancer. PMID- 26137518 TI - Destination Airway: Tracking Granulocytes in Asthma. PMID- 26137519 TI - Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles. AB - Epstein Barr virus (EBV) persists as a latent herpes virus infection in the majority of the adult human population. The virus can reactivate from this latent infection into lytic replication for virus particle production. Here, we report that autophagic membranes, which engulf cytoplasmic constituents during macroautophagy and transport them to lysosomal degradation, are stabilized by lytic EBV replication in infected epithelial and B cells. Inhibition of autophagic membrane formation compromises infectious particle production and leads to the accumulation of viral DNA in the cytosol. Vice versa, pharmacological stimulation of autophagic membrane formation enhances infectious virus production. Atg8/LC3, an essential macroautophagy protein and substrate anchor on autophagic membranes, was found in virus preparations, suggesting that EBV recruits Atg8/LC3 coupled membranes to its envelope in the cytosol. Our data indicate that EBV subverts macroautophagy and uses autophagic membranes for efficient envelope acquisition during lytic infection. PMID- 26137520 TI - Large Isoform of Mammalian Relative of DnaJ is a Major Determinant of Human Susceptibility to HIV-1 Infection. AB - Individual differences in susceptibility to human immunodeficiency virus type 1 (HIV-1) infection have been of interest for decades. We aimed to determine the contribution of large isoform of Mammalian DnaJ (MRJ-L), a HIV-1 Vpr-interacting cellular protein, to this natural variation. Expression of MRJ-L in monocyte derived macrophages was significantly higher in HIV-infected individuals (n = 31) than their uninfected counterparts (n = 27) (p = 0.009). Fifty male homosexual subjects (20 of them are HIV-1 positive) were further recruited to examine the association between MRJ-L levels and occurrence of HIV infection. Bayesian multiple logistic regression revealed that playing a receptive role and increased levels of MRJ-L in macrophages were two risk factors for HIV-1 infection. A 1% rise in MRJ-L expression was associated with a 1.13 fold (95% CrI 1.06-1.29) increase in odds of contracting HIV-1 infection. Ex vivo experiments revealed that MRJ-L facilitated Vpr-dependent nuclear localization of virus. Infection of macrophage-tropic strain is a critical step in HIV-1 transmission. MRJ-L is a critical factor in this process; hence, subjects with higher macrophage MRJ-L levels are more vulnerable to HIV-1 infection. PMID- 26137521 TI - Measles Epidemics Among Children in Vietnam: Genomic Characterization of Virus Responsible for Measles Outbreak in Ho Chi Minh City, 2014. AB - BACKGROUND: Measles remains poorly controlled in Southeast Asia, including Vietnam. OBJECTIVES: The aim of this study was to characterize genes of virus responsible for a measles outbreak among children in Vietnam in 2014. STUDY DESIGN: Throat swab samples were collected from 122 pediatric patients with suspected measles. Furthermore, peripheral blood mononuclear cells (PBMCs) from 31 of these cases were also collected. Measles virus (MV) RNA was obtained directly from the clinical specimens, amplified by PCR, and then the N and H genes were sequenced. RESULTS: MV RNA was detectable in throat swabs from all 122 patients tested. Positive-strand viral RNA, which indicates the intermediate replicative form of MV, was also detected in PBMCs from all 31 cases from whom these cells were collected. One hundred and eighteen strains with the N gene were obtained by RT-PCR and sequenced. Using phylogenetic analysis with measles reference sequences, all of the Vietnamese strains were found to be genotype D8. However, all strains formed a distinct cluster within the genotype D8 group (D8 VNM) suggesting their own lineage. This distinct cluster was supported by a branch with a 99% bootstrap value and 3.3% nucleotide divergence in the N-450 region of the N gene from the D8 reference strain. Notably, all of the D8-VNM variant strains represented unique amino acid sequences consisting of R442, S451 and G452 in the N-450 region of the N gene. CONCLUSIONS: Measles viruses responsible for outbreaks in Southern Vietnam belonged to a genotype D8 variant group which had unique amino acid sequences in the N gene. Our report provides important genomic information about the virus for measles elimination in Southeast Asia. PMID- 26137522 TI - Prediction of Clinical Outcome for All Stages and Multiple Cell Types of Non small Cell Lung Cancer in Five Countries Using Lung Cancer Prognostic Index. AB - Lung cancer is a commonly diagnosed cancer. In this era of personalized medicine, genetic predictive models are becoming increasingly important. However, many current predictive models fail verification tests due to small sample sizes and institutional biases. We collected 17 gene expression datasets from public databases to generate our largest training and testing cohorts. After successfully eliminating institutional variations and merging multiple datasets, we generated a training cohort of 1073 and a testing cohort of 659. Using Siggenes, univariate and multivariate analyses, we identified seven gene signatures, and combined them with the clinical parameter age and stage to design the lung cancer prognostic index (LCPI). Using LCPI, we could differentiate lung cancer patients into three risk groups and predict patient survival probabilities at 10 and 15 year post-surgical resection. We extensively verified the predictive ability of LCPI for overall and recurrence free survival using 6 other datasets from five different countries. PMID- 26137523 TI - Imaging Inflammation in Asthma: Real Time, Differential Tracking of Human Neutrophil and Eosinophil Migration in Allergen Challenged, Atopic Asthmatics in Vivo. AB - BACKGROUND: It is important to study differential inflammatory cellular migration, particularly of eosinophils and neutrophils, in asthma and how this is influenced by environmental stimuli such as allergen exposure and the effects of anti asthma therapy. METHODS: We isolated blood neutrophils and eosinophils from 12 atopic asthmatic human volunteers (Group 1 - four Early Allergic Responders unchallenged (EAR); Group 2 - four Early and Late Allergic Responders (LAR) challenged; Group 3 - four EAR and LAR challenged and treated with systemic corticosteroids) using cGMP CD16 CliniMACS. Cells were isolated prior to allergen challenge where applicable, labelled with (99m)Tc-HMPAO and then re-infused intravenously. The kinetics of cellular influx/efflux into the lungs and other organs were imaged via scintigraphy over 4 h, starting at 5 to 6 h following allergen challenge where applicable. RESULTS: Neutrophils and eosinophils were isolated to a mean (SD) purity of 98.36% (1.09) and 96.31% (3.0), respectively. Asthmatic neutrophils were activated at baseline, mean (SD) CD11b(High) cells 46 (10.50) %. Isolation and radiolabelling significantly increased their activation to > 98%. Eosinophils were not activated at baseline, CD69(+) cells 1.9 (0.6) %, increasing to 38 (3.46) % following isolation and labelling. Analysis of the kinetics of net eosinophil and neutrophil lung influx/efflux conformed to a net exponential clearance with respective mean half times of clearance 6.98 (2.18) and 14.01 (2.63) minutes for Group 1, 6.03 (0.72) and 16.04 (2.0) minutes for Group 2 and 5.63 (1.20) and 14.56 (3.36) minutes for Group 3. These did not significantly differ between the three asthma groups (p > 0.05). CONCLUSIONS: Isolation and radiolabelling significantly increased activation of eosinophils (CD69) and completely activated neutrophils (CD11b(High)) in all asthma groups. Net lung neutrophil efflux was significantly slower than that of eosinophils in all asthma study groups. There was a trend for pre-treatment with systemic corticosteroids to reduce lung retention of eosinophils following allergen challenge. PMID- 26137524 TI - mTOR Inhibitors in Cancer: What Can We Learn from Exceptional Responses? PMID- 26137525 TI - Treatment of Acromegaly: Are We Satisfied With the Current Outcome? PMID- 26137526 TI - Hypermethylation of RASAL1: A Key for Renal Fibrosis. PMID- 26137527 TI - How Can We Predict Treatment Outcome for Depression? PMID- 26137528 TI - Developing Strategies to Treat Asthma Exacerbations Caused by Rhinovirus. PMID- 26137529 TI - SNaPshot as a Valuable Option for the Identification of Mutations in Myeloma. PMID- 26137530 TI - Whole Genome Sequencing in Cancer Clinics. PMID- 26137531 TI - The Other Face of Artesunate: Southern Drug to Treat Northern Diseases. PMID- 26137532 TI - Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder. AB - BACKGROUND: Less than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs. METHODS: 157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. A score at week 8 of 7 or less on the 17 item Hamilton Rating Scale for Depression defined remission. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity. These decision trees were tested for replication in the remaining participants. FINDINGS: Overall, 35% of all participants achieved remission. ROC analyses identified two decision trees that predicted a high probability of non-remission and that were replicated: 1. Left middle frontal volume < 14 . 8 mL & right angular gyrus volume > 6 . 3 mL identified 55% of non-remitters with 85% accuracy; and 2. Fractional anisotropy values in the left cingulum bundle < 0 . 63, right superior fronto-occipital fasciculus < 0 . 54 and right superior longitudinal fasciculus < 0 . 50 identified 15% of the non-remitters with 84% accuracy. All participants who met criteria for both decision trees were correctly identified as non-remitters. INTERPRETATION: Pretreatment MRI measures seem to reliably identify a subset of patients who do not remit with a first step medication that includes one of these commonly used medications. Findings are consistent with a neuroanatomical basis for non-remission in depressed patients. FUNDING: Brain Resource Ltd is the sponsor for the iSPOT-D study (NCT00693849). PMID- 26137534 TI - Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis. AB - BACKGROUND: Development of congenital rubella syndrome associated with rubella virus infection during pregnancy is clinically important, but the pathogenicity of the virus remains unclear. METHODS: Pathological examination was conducted on 3 aborted fetuses with congenital rubella infection. FINDINGS: At autopsy, all 3 aborted fetuses showed congenital cataract confirmed by gross observation. Rubella virus infection occurred via systemic organs including circulating hematopoietic stem cells confirmed by immunohistochemical and molecular investigations, and major histopathogical changes were found in the liver. It is noteworthy that the virus infected the ciliary body of the eye, suggesting a possible cause of cataracts. INTERPRETATION: Our study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis. PMID- 26137533 TI - CD8(+) T-cell Cytotoxic Capacity Associated with Human Immunodeficiency Virus-1 Control Can Be Mediated through Various Epitopes and Human Leukocyte Antigen Types. AB - Understanding natural immunologic control over Human Immunodeficiency Virus (HIV) 1 replication, as occurs in rare long-term nonprogressors/elite controllers (LTNP/EC), should inform the design of efficacious HIV vaccines and immunotherapies. Durable control in LTNP/EC is likely mediated by highly functional virus-specific CD8(+) T-cells. Protective Human Leukocyte Antigen (HLA) class I alleles, like B*27 and B*57, are present in most, but not all LTNP/EC, providing an opportunity to investigate features shared by their HIV specific immune responses. To better understand the contribution of epitope targeting and conservation to immune control, we compared the CD8(+) T-cell specificity and function of B*27/57(neg) LTNP/EC (n = 23), B*27/57(pos) LTNP/EC (n = 23) and B*27/57(neg) progressors (n = 13). Fine mapping revealed 11 previously unreported immunodominant responses. Although B*27/57(neg) LTNP/EC did not target more highly conserved epitopes, their CD8(+) T-cell cytotoxic capacity was significantly higher than progressors. Similar to B*27/57(pos) LTNP/EC, this superior cytotoxicity was mediated by preferential expansion of immunodominant responses and lysis through the predicted HLA. These findings suggest that increased CD8(+) T-cell cytotoxic capacity is a common mechanism of control in most LTNP/EC regardless of HLA type. They also suggest that potent cytotoxicity can be mediated through various epitopes and HLA molecules and could, in theory, be induced in most people. PMID- 26137535 TI - Rhinovirus-induced VP1-specific Antibodies are Group-specific and Associated With Severity of Respiratory Symptoms. AB - BACKGROUND: Rhinoviruses (RVs) are a major cause of common colds and induce exacerbations of asthma and chronic inflammatory lung diseases. METHODS: We expressed and purified recombinant RV coat proteins VP1-4, non-structural proteins as well as N-terminal fragments of VP1 from four RV strains (RV14, 16, 89, C) covering the three known RV groups (RV-A, RV-B and RV-C) and measured specific IgG-subclass-, IgA- and IgM-responses by ELISA in subjects with different severities of asthma or without asthma before and after experimental infection with RV16. FINDINGS: Before infection subjects showed IgG1 > IgA > IgM > IgG3 cross-reactivity with N-terminal fragments from the representative VP1 proteins of the three RV groups. Antibody levels were higher in the asthmatic group as compared to the non-asthmatic subjects. Six weeks after infection with RV16, IgG1 antibodies showed a group-specific increase towards the N-terminal VP1 fragment, but not towards other capsid and non-structural proteins, which was highest in subjects with severe upper and lower respiratory symptoms. INTERPRETATION: Our results demonstrate that increases of antibodies towards the VP1 N-terminus are group-specific and associated with severity of respiratory symptoms and suggest that it may be possible to develop serological tests for identifying causative RV groups. PMID- 26137536 TI - Clinical Grade "SNaPshot" Genetic Mutation Profiling in Multiple Myeloma. AB - Whole genome sequencing studies have identified several oncogenic mutations in multiple myeloma (MM). As MM progresses, it evolves genetically underscoring the need to have tools for rapid detection of targetable mutations to optimize individualized treatment. Massachusetts General Hospital (MGH) has developed a Clinical Laboratory Improvement Amendments (CLIA)-approved, high-throughput, genotyping platform to determine the mutation status of a panel of known oncogenes. Sequence analysis using SNaPshot on DNA extracted from bone marrow and extramedullary plasmacytomas is feasible and leads to the detection of potentially druggable mutations. Screening MM patients for somatic mutations in oncogenes may provide novel targets leading to additional therapies for this patient population. PMID- 26137538 TI - The Fight Against Cervical Cancer. PMID- 26137537 TI - A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. AB - BACKGROUND: Artesunate is an antimalarial agent with broad anti-cancer activity in in vitro and animal experiments and case reports. Artesunate has not been studied in rigorous clinical trials for anticancer effects. AIM: To determine the anticancer effect and tolerability of oral artesunate in colorectal cancer (CRC). METHODS: This was a single centre, randomised, double-blind, placebo-controlled trial. Patients planned for curative resection of biopsy confirmed single primary site CRC were randomised (n = 23) by computer-generated code supplied in opaque envelopes to receive preoperatively either 14 daily doses of oral artesunate (200 mg; n = 12) or placebo (n = 11). The primary outcome measure was the proportion of tumour cells undergoing apoptosis (significant if > 7% showed Tunel staining). Secondary immunohistochemical outcomes assessed these tumour markers: VEGF, EGFR, c-MYC, CD31, Ki67 and p53, and clinical responses. FINDINGS: 20 patients (artesunate = 9, placebo = 11) completed the trial per protocol. Randomization groups were comparable clinically and for tumour characteristics. Apoptosis in > 7% of cells was seen in 67% and 55% of patients in artesunate and placebo groups, respectively. Using Bayesian analysis, the probabilities of an artesunate treatment effect reducing Ki67 and increasing CD31 expression were 0.89 and 0.79, respectively. During a median follow up of 42 months 1 patient in the artesunate and 6 patients in the placebo group developed recurrent CRC. INTERPRETATION: Artesunate has anti-proliferative properties in CRC and is generally well tolerated. PMID- 26137540 TI - Erythroid Adhesion Molecules in Sickle Cell Anaemia Infants: Insights Into Early Pathophysiology. AB - Sickle cell anaemia (SCA) results from a single mutation in the beta globin gene. It is seldom symptomatic in the first semester of life. We analysed the expression pattern of 9 adhesion molecules on red blood cells, in a cohort of 54 SCA and 17 non-SCA very young infants of comparable age (median 144 days, 81 196). Haemoglobin F (HbF) level was unsurprisingly elevated in SCA infants (41.2% +/- 11.2) and 2-4 fold higher than in non-SCA infants, yet SCA infants presented significantly decreased Hb level and increased reticulocytosis. Cytometry analysis evidenced a specific expression profile on reticulocytes of SCA infants, with notably an increased expression of the adhesion molecules Lu/BCAM, ICAM-4 and LFA-3, both in percentage of positive cells and in surface density. No significant difference was found on mature red cells. Our findings demonstrate the very early onset of reticulocyte membrane modifications in SCA asymptomatic infants and allow an insight into the first pathological changes with the release of stress reticulocytes expressing a distinctive profile of adhesion molecules. PMID- 26137539 TI - Measurements of Functional Responses in Human Primary Lung Cells as a Basis for Personalized Therapy for Cystic Fibrosis. AB - BACKGROUND: The best investigational drug to treat cystic fibrosis (CF) patients with the most common CF-causing mutation (F508del) is VX-809 (lumacaftor) which recently succeeded in Phase III clinical trial in combination with ivacaftor. This corrector rescues F508del-CFTR from its abnormal intracellular localization to the cell surface, a traffic defect shared by all Class II CFTR mutants. Our goal here is to test the efficacy of lumacaftor in other Class II mutants in primary human bronchial epithelial (HBE) cells derived from CF patients. METHODS: The effect of lumacaftor was investigated in primary HBE cells from non-CF and CF patients with F508del/F508del, A561E/A561E, N1303K/G542X, F508del/G542X and F508del/Y1092X genotypes by measurements of Forskolin plus Genistein-inducible equivalent short-circuit current (Ieq-SC-Fsk + Gen) in perfused open-circuit Ussing chambers. Efficacy of corrector C18 was also assessed on A561E/A561E and F508del/F508del cells. RESULTS: Our data indicate that A561E (when present in both alleles) responds positively to lumacaftor treatment at equivalent efficacy of F508del in primary HBE cells. Similarly, lumacaftor has a positive impact on Y1092X, but not on N1303K. Our data also show that cells with only one copy of F508del-CFTR respond less to VX-809. Moreover, there is great variability in lumacaftor responses among F508del-homozygous cells from different donors. Compound C18 failed to rescue A561E-CFTR but not in F508del-CFTR, thus plausibly it has a different mechanism of action distinct from lumacaftor. CONCLUSIONS: CF patients with A561E (and likely also those with Y1029X) can potentially benefit from lumacaftor. Moreover, the methodology used here exemplifies how ex vivo approaches may apply personalized therapies to CF and possibly other respiratory diseases. PMID- 26137542 TI - Novel Therapies for Heart Failure. PMID- 26137541 TI - Biomarkers Can Identify Pulmonary Tuberculosis in HIV-infected Drug Users Months Prior to Clinical Diagnosis. AB - BACKGROUND: Current diagnostic tests cannot identify which infected individuals are at risk for progression to tuberculosis (TB). Our aim was to identify biomarkers which can predict the development of TB prior to clinical diagnosis. METHOD: In a retrospective case-control study, RNA of 14 HIV-infected drug users obtained before TB diagnosis (cases) and of 15 who did not develop TB (controls) was analyzed for the expression of 141 genes by dcRT-MLPA followed by Lasso regression analysis. FINDINGS: A combined analysis of IL13 and AIRE had the highest discriminatory power to identify cases up to 8 months prior to clinical diagnosis. Cases expressing IL13 had a gene expression pattern strongly enriched for type I IFN related signaling genes, suggesting that these genes represent processes that contribute to TB pathogenesis. INTERPRETATION: We here demonstrated that biomarkers, such as IL13-AIRE, can identify individuals that progress to TB within a high risk population, months prior to clinical diagnosis. PMID- 26137543 TI - 2015: The Year of Anti-PD-1/PD-L1s Against Melanoma and Beyond. PMID- 26137544 TI - Recent Advances from the Bench Toward the Bedside in Alzheimer's Disease. PMID- 26137545 TI - Cyclin D1 Again Caught in the Act: Dyrk1a Links G1 and Neurogenesis in Down Syndrome. PMID- 26137546 TI - Does reverse transport of dopamine play a role in autism? PMID- 26137547 TI - Predicting CFTR activity with front-runner cystic fibrosis drugs. PMID- 26137548 TI - High Foetal Haemoglobin in Sickle Cell Disease: Not so Protective? PMID- 26137549 TI - MTHFR polymorphisms in primary varicose vein disorder. PMID- 26137550 TI - Circulating prostaglandins as biomarkers for colorectal cancer? PMID- 26137551 TI - Early Identification of Progressive TB Disease Using Host Biomarkers. PMID- 26137552 TI - 3-D Imaging Reveals Participation of Donor Islet Schwann Cells and Pericytes in Islet Transplantation and Graft Neurovascular Regeneration. AB - The primary cells that participate in islet transplantation are the endocrine cells. However, in the islet microenvironment, the endocrine cells are closely associated with the neurovascular tissues consisting of the Schwann cells and pericytes, which form sheaths/barriers at the islet exterior and interior borders. The two cell types have shown their plasticity in islet injury, but their roles in transplantation remain unclear. In this research, we applied 3 dimensional neurovascular histology with cell tracing to reveal the participation of Schwann cells and pericytes in mouse islet transplantation. Longitudinal studies of the grafts under the kidney capsule identify that the donor Schwann cells and pericytes re-associate with the engrafted islets at the peri-graft and perivascular domains, respectively, indicating their adaptability in transplantation. Based on the morphological proximity and cellular reactivity, we propose that the new islet microenvironment should include the peri-graft Schwann cell sheath and perivascular pericytes as an integral part of the new tissue. PMID- 26137555 TI - Progress and Roadblocks Along the Pathway to Multiple Sclerosis Treatment. PMID- 26137554 TI - Morphology and Progression in Primary Varicose Vein Disorder Due to 677C>T and 1298A>C Variants of MTHFR. AB - BACKGROUND: Clinical assessment and prognostic stratification of primary varicose veins have remained controversial and the molecular pathogenesis is unknown. Previous data have suggested a contribution of the MTHFR (methylenetetrahydrofolate reductase) polymorphism c.677C>T. METHODS: We collected blood and vein specimens from 159 consecutive patients undergoing varicose vein surgery, or autologous vein reconstruction for arterial occlusive disease as controls. We compared the frequencies of c.677C>T and another polymorphism of MTHFR, c.1298A>C, with morphology and types of complicated disease. Morphology was recorded as a trunk or perforator type and peripheral congestive complication was defined as chronic venous insufficiency (CEAP C3-6) associated with edema and skin manifestations. FINDINGS: Multivariate analysis of genotypes for c.677C>T and c.1298A>C indicated that c.677C>T was associated significantly with the trunk phenotype (43/53 patients, 81%, p < 0.01), while c.1298A>C was associated significantly with the perforator phenotype (18/24 patients, 75%, p < 0.01) of primary varicose veins. Accordingly, when both c.677C>T and c.1298A>C displayed a heterozygous genotype, the patients were more likely to present with both phenotypes. Additionally, c.1298A>C was found to be strongly linked to the congestive complication (34/51 patients, 67%, p < 0.01). INTERPRETATION: Both polymorphisms of MTHFR may be involved in the morphological specification of primary varicose veins and contribute to the development of complicated disease. FUNDING: None. PMID- 26137553 TI - DYRK1A-mediated Cyclin D1 Degradation in Neural Stem Cells Contributes to the Neurogenic Cortical Defects in Down Syndrome. AB - Alterations in cerebral cortex connectivity lead to intellectual disability and in Down syndrome, this is associated with a deficit in cortical neurons that arises during prenatal development. However, the pathogenic mechanisms that cause this deficit have not yet been defined. Here we show that the human DYRK1A kinase on chromosome 21 tightly regulates the nuclear levels of Cyclin D1 in embryonic cortical stem (radial glia) cells, and that a modest increase in DYRK1A protein in transgenic embryos lengthens the G1 phase in these progenitors. These alterations promote asymmetric proliferative divisions at the expense of neurogenic divisions, producing a deficit in cortical projection neurons that persists in postnatal stages. Moreover, radial glial progenitors in the Ts65Dn mouse model of Down syndrome have less Cyclin D1, and Dyrk1a is the triplicated gene that causes both early cortical neurogenic defects and decreased nuclear Cyclin D1 levels in this model. These data provide insights into the mechanisms that couple cell cycle regulation and neuron production in cortical neural stem cells, emphasizing that the deleterious effect of DYRK1A triplication in the formation of the cerebral cortex begins at the onset of neurogenesis, which is relevant to the search for early therapeutic interventions in Down syndrome. PMID- 26137556 TI - Innovations in Tuberculosis Diagnostics: Progress and Translational Challenges. PMID- 26137557 TI - Fanning the Fire: Can Methemoglobin Enhance Neutrophil Activation? PMID- 26137558 TI - Will Genome Analysis Elucidate Evolution, Global Transmission and Virulence of Neisseria Meningitidis Lineages? PMID- 26137559 TI - Deciphering How HIV-1 Intersubtype Recombination Shapes Viral Fitness and Disease Progression. PMID- 26137560 TI - Is BECN1 a Target Gene of Chromosome 17q21 Alteration in Breast Cancer? PMID- 26137561 TI - Evaluation of Biomarkers for HER3-targeted Therapies in Cancer. PMID- 26137562 TI - Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System. AB - BACKGROUND: Haemolytic infection lyses red blood cells, releasing haemoglobin (Hb) into the plasma. Although recent studies showed that immune cells recognize redox-active cytotoxic extracellular Hb (metHb) bound to pathogen-associated molecular patterns (PAMPs), currently available information is limited to experiments performed in defined conditions using single cell lines. Therefore, a systemic approach targeting primary whole blood cells is required to better understand the cellular immune defence against metHb and PAMPs, when under a haemolytic infection. METHODS: We investigated how human white blood cells, including neutrophils, respond to metHb and lipoteichoic acid (LTA) by measuring reactive oxygen species (ROS), signalling mediators (ERK and p38), NF-kappaB, cytokines, elastase secretion and cell activation markers. FINDINGS: metHb activates NF-kappaB in TLR2-expressing HEK293 cells but not in normal or TLR9 expressing HEK293 cells. Treatment of isolated neutrophils with metHb increased production of ROS and expressions of IL-8, TNFalpha, and CD11b, which were further enhanced by metHb + LTA complex. While LTA stimulated the survival of neutrophils, it caused apoptotic cell death when complexed with metHb. The activation of neutrophils by metHb + LTA was subdued by the presence of other types of white blood cells. INTERPRETATION: metHb and metHb + LTA complex are ligands of TLR2, inducing an unconventional TLR signalling pathway. Neutrophils are a highly sensitive cell type to metHb + LTA complex. During a haemolytic infection, white blood cells in the vicinity crosstalk to modulate neutrophil TLR signalling induced by metHb and LTA. PMID- 26137565 TI - Autism: Fitting the Pieces Together. PMID- 26137563 TI - CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba. AB - BACKGROUND: Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. METHODS: Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. FINDINGS: Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. INTERPRETATION: CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba. PMID- 26137566 TI - IL-6 Blockade as a Therapeutic Approach for Duchenne Muscular Dystrophy. PMID- 26137564 TI - Clinical Translation and Validation of a Predictive Biomarker for Patritumab, an Anti-human Epidermal Growth Factor Receptor 3 (HER3) Monoclonal Antibody, in Patients With Advanced Non-small Cell Lung Cancer. AB - BACKGROUND: During early clinical development, prospective identification of a predictive biomarker and validation of an assay method may not always be feasible. Dichotomizing a continuous biomarker measure to classify responders also leads to challenges. We present a case study of a prospective-retrospective approach for a continuous biomarker identified after patient enrollment but defined prospectively before the unblinding of data. An analysis of the strengths and weaknesses of this approach and the challenges encountered in its practical application are also provided. METHODS: HERALD (NCT02134015) was a double-blind, phase 2 study in patients with non-small cell lung cancer (NSCLC) randomized to erlotinib with placebo or with high or low doses of patritumab, a monoclonal antibody targeted against human epidermal growth factor receptor 3 (HER3). While the primary objective was to assess safety and progression-free survival (PFS), a secondary objective was to determine a single predictive biomarker hypothesis to identify subjects most likely to benefit from the addition of patritumab. Although not identified as the primary biomarker in the study protocol, on the basis of preclinical results from 2 independent laboratories, expression levels of the HER3 ligand heregulin (HRG) were prospectively declared the predictive biomarker before data unblinding but after subject enrollment. An assay to measure HRG mRNA was developed and validated. Other biomarkers, such as epidermal growth factor receptor (EGFR) mutation status, were also evaluated in an exploratory fashion. The cutoff value for high vs. low HRG mRNA levels was set at the median delta threshold cycle. A maximum likelihood analysis was performed to evaluate the provisional cutoff. The relationship of HRG values to PFS hazard ratios (HRs) was assessed as a measure of internal validation. Additional NSCLC samples were analyzed to characterize HRG mRNA distribution. RESULTS: The subgroup of patients with high HRG mRNA levels ("HRG-high") demonstrated clinical benefit from patritumab treatment with HRs of 0.37 (P = 0.0283) and 0.29 (P = 0.0027) in the high- and low-dose patritumab arms, respectively. However, only 102 of the 215 randomized patients (47.4%) had sufficient tumor samples for HRG mRNA measurement. Maximum likelihood analysis showed that the provisional cutoff was within the optimal range. In the placebo arm, the HRG-high subgroup demonstrated worse prognosis compared with HRG-low. A continuous relationship was observed between increased HRG mRNA levels and lower HR. Additional NSCLC samples (N = 300) demonstrated a similar unimodal distribution to that observed in this study, suggesting that the defined cutoff may be applicable to future NSCLC studies. CONCLUSIONS: The prospective-retrospective approach was successful in clinically validating a probable predictive biomarker. Post hoc in vitro studies and statistical analyses permitted further testing of the underlying assumptions. However, limitations of this analysis include the incomplete collection of adequate tumor tissue and a lack of stratification. In a phase 3 study, findings are being confirmed, and the HRG cutoff value is being further refined. CLINICALTRIALSGOV NUMBER: NCT02134015. PMID- 26137567 TI - Mitochondrial Manipulation and the Quest for Alzheimer's Treatments. PMID- 26137568 TI - Radiation Sensitization of Leukemic Cells for Low Dose Total Body Irradiation. PMID- 26137569 TI - Detection of Mutant RAS Subpopulations in Colorectal Cancer Patients. PMID- 26137570 TI - Translational Positioning of Janus Kinase (JAK) Inhibitors in Alopecia Areata. PMID- 26137571 TI - Beta-2 Agonism: A Potential Therapeutic Target for Dyslipidemia. PMID- 26137573 TI - Clinical Validation of a Multiplex Kit for RAS Mutations in Colorectal Cancer: Results of the RASKET (RAS KEy Testing) Prospective, Multicenter Study. AB - BACKGROUND: RAS (KRAS and NRAS) testing is required to predict anti-epidermal growth factor receptor (EGFR) treatment efficacy in metastatic colorectal cancer (CRC). Although direct sequencing (DS) with manual microdissection (MMD) is widely used, a diagnostic kit providing rapid detections of RAS mutations would be clinically beneficial. We evaluated the MEBGEN(TM) RASKET KIT (RASKET KIT), a multiplex assay using PCR-reverse sequence specific oligonucleotide and xMAP((r)) technology to concurrently detect exon 2, 3, and 4 RAS mutations in a short turnaround time (4.5 h/96-specimens). METHODS: Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 308 consenting patients with histologically confirmed CRC at six hospitals in Japan. For the RASKET KIT, we used only 50-100 ng DNA from each FFPE specimen not processed by MMD. The primary endpoint was the concordance rate between RAS mutations identified with the RASKET KIT and two reference assays (DS with MMD and TheraScreen((r)) K-RAS Mutation Kit). As the secondary endpoints, we evaluated the concordance rate between DS and the RASKET KIT for RAS mutations in the wild-type KRAS exon 2 population and the genotyping performance of the RASKET KIT compared with DS. FINDINGS: Among 307 analyzable specimens, the reference assays detected 140 (45.6%, 140/307) RAS mutations: 111 KRAS exon 2 and 29 other (minor) RAS mutations. The RASKET KIT detected 143 (46.6%, 143/307) mutations: 114 KRAS exon 2 and 29 minor RAS mutations. The between-method concordance rate was 96.7% (297/307) (95% CI: 94.1-98.4%). Minor RAS mutations were detected in 15.7% (30/191) of the wild-type KRAS exon 2 population (n = 191); the concordance rate was 98.4% (188/191) (95% CI: 95.5 99.7%). The concordance rate of RAS genotyping was 100% (139/139) (95% CI: 97 100%). INTERPRETATION: The RASKET KIT provides rapid and precise detections of RAS mutations and consequently, quicker and more effective anti-EGFR therapy for CRC (Study ID: UMIN000011784). FUNDING: Medical & Biological Laboratories Co., Ltd. (MBL). MBL had roles in study design, data collection, data analysis, and writing of the report for the study. PMID- 26137572 TI - Functional and Morphological Improvement of Dystrophic Muscle by Interleukin 6 Receptor Blockade. AB - The anti-inflammatory agents glucocorticoids (GC) are the only available treatment for Duchenne muscular dystrophy (DMD). However, long-term GC treatment causes muscle atrophy and wasting. Thus, targeting specific mediator of inflammatory response may be more specific, more efficacious, and with fewer side effects. The pro-inflammatory cytokine interleukin (IL) 6 is overproduced in patients with DMD and in the muscle of mdx, the animal model for human DMD. We tested the ability of inhibition of IL6 activity, using an interleukin-6 receptor (Il6r) neutralizing antibody, to ameliorate the dystrophic phenotype. Blockade of endogenous Il6r conferred on dystrophic muscle resistance to degeneration and alleviated both morphological and functional consequences of the primary genetic defect. Pharmacological inhibition of IL6 activity leaded to changes in the dystrophic muscle environment, favoring anti-inflammatory responses and improvement in muscle repair. This resulted in a functional homeostatic maintenance of dystrophic muscle. These data provide an alternative pharmacological strategy for treatment of DMD and circumvent the major problems associated with conventional therapy. PMID- 26137574 TI - Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib. AB - BACKGROUND: Alopecia areata (AA) is an autoimmune disease resulting in hair loss with devastating psychosocial consequences. Despite its high prevalence, there are no FDA-approved treatments for AA. Prior studies have identified a prominent interferon signature in AA, which signals through JAK molecules. METHODS: A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome. In vivo, preclinical studies were conducted using the C3H/HeJ AA mouse model to assess the mechanism of clinical improvement by baricitinib. FINDINGS: The patient exhibited a striking improvement of his AA on baricitinib over several months. In vivo studies using the C3H/HeJ mouse model demonstrated a strong correlation between resolution of the interferon signature and clinical improvement during baricitinib treatment. INTERPRETATION: Baricitinib may be an effective treatment for AA and warrants further investigation in clinical trials. PMID- 26137575 TI - The Lipid-lowering Effects of R-bambuterol in Healthy Chinese Volunteers: A Randomized Phase I Clinical Study. AB - BACKGROUND: Existing treatments are inadequate for patients at high risk of coronary heart disease caused by elevated levels of plasma low-density lipoprotein cholesterol (LDL-C). Bambuterol is a prodrug of beta2-agonist commonly used for the treatment of asthma and chronic obstructive pulmonary disease (COPD) with the advantage of once daily dosing and favorable side effect profile. The potential lipid-lowering effects of bambuterol were unclear, possibly due to the racemic bambuterol (rac-bambuterol) that was used in previous studies. METHODS: The lipid-lowering effects of R-bambuterol were examined in a randomized phase I trial in 48 healthy Chinese volunteers aged 18-45 years. Participants were randomly assigned to five groups to receive a single dose (2.5 mg, 5 mg or 10 mg) or multiple doses (5 mg) of oral medications of R-bambuterol, or a single dose of rac-bambuterol (10 mg). Plasma lipid levels were measured at baseline, time to peak concentration (Tmax) and 24 h after the treatment. FINDINGS: Administration of a single-dose of R-bambuterol resulted in dose dependent reductions in the levels of plasma LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) at Tmax. Levels of LDL-C exhibited the most reductions, which were statistically significant in all three single-dose R-bambuterol groups (all P values < 0.05). R-bambuterol was more potent in LDL-C lowering compared to rac-bambuterol at Tmax (P = 0.08). At 24 h after dosing, the significant lipid lowering effects of R-bambuterol sustained for LDL-C (P = 0.01), ApoB (P = 0.001) and ApoA1 (P = 0.03), but not for HDL-C. The ratio of ApoA1/ApoB was marginally increased (P = 0.06). In the multiple-dose group, LDL-C levels again were significantly reduced (all P values < 0.05), whereas the ratios of ApoA1/ApoB were marginally increased. INTERPRETATION: R-bambuterol can lower the plasma levels of LDL-C, and marginally raise the ratio of ApoA1/ApoB (indicator of HDL C/LDL-C) with both a single dose and multiple doses. R-bambuterol was more potent in LDL-C lowering than rac-bambuterol. PMID- 26137576 TI - CRISPR-Cas9 Based Therapeutics: Not So Fast. PMID- 26137577 TI - Nanomedicine for Combination Therapy of Cancer. PMID- 26137578 TI - Pancreatic Alpha Cells Hold the Key to Survival. PMID- 26137579 TI - New Biomarkers for Early Detection of Hepatocellular Carcinoma. PMID- 26137580 TI - COX-2 and EGFR: Partners in Crime Split by Aspirin. PMID- 26137581 TI - Membranous Nephropathy: The Journey Continues .... PMID- 26137582 TI - Mesenchymal Stem Cells & Endothelial Function. PMID- 26137583 TI - Pancreatic alpha Cells are Resistant to Metabolic Stress-induced Apoptosis in Type 2 Diabetes. AB - Pancreatic alpha cells are exposed to metabolic stress during the evolution of type 2 diabetes (T2D), but it remains unclear whether this affects their survival. We used electron microscopy to search for markers of apoptosis and endoplasmic reticulum (ER) stress in alpha and beta cells in islets from T2D or non-diabetic individuals. There was a significant increase in apoptotic beta cells (from 0.4% in control to 6.0% in T2D), but no alpha cell apoptosis. We observed, however, similar ER stress in alpha and beta cells from T2D patients. Human islets or fluorescence-activated cell sorting (FACS)-purified rat beta and alpha cells exposed in vitro to the saturated free fatty acid palmitate showed a similar response as the T2D islets, i.e. both cell types showed signs of ER stress but only beta cells progressed to apoptosis. Mechanistic experiments indicate that this alpha cell resistance to palmitate-induced apoptosis is explained, at least in part, by abundant expression of the anti-apoptotic protein Bcl2l1 (also known as Bcl-xL). PMID- 26137584 TI - Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4 MLL Fusion Protein. AB - We have recently demonstrated that Taspase1-mediated cleavage of the AF4-MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (alphabetabetaalpha). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4-MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4 MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4-MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4-MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed. PMID- 26137586 TI - A Hot-spot of In-frame Duplications Activates the Oncoprotein AKT1 in Juvenile Granulosa Cell Tumors. AB - BACKGROUND: Ovarian granulosa cell tumors are the most common sex-cord stromal tumors and have juvenile (JGCTs) and adult forms. In a previous study we reported the occurrence of activating somatic mutations of Galphas, which transduces mitogenic signals, in 30% of the analyzed JGCTs. METHODS: We have searched for alterations in other proteins involved in ovarian mitogenic signaling. We focused on the PI3K-AKT axis. As we found mutations in AKT1, we analyzed the subcellular localization of the mutated proteins and performed functional explorations using Western-blot and luciferase assays. FINDINGS: We detected in-frame duplications affecting the pleckstrin-homology domain of AKT1 in more than 60% of the tumors occurring in girls under 15 years of age. The somatic status of the mutations was confirmed when peritumoral DNA was available. The JGCTs without duplications carried point mutations affecting highly conserved residues. Several of these substitutions were somatic lesions. The mutated proteins carrying the duplications had a non-wild-type subcellular distribution, with a marked enrichment at the plasma membrane. This led to a striking degree of AKT1 activation demonstrated by a strong phosphorylation level and by reporter assays. INTERPRETATION: Our study incriminates somatic mutations of AKT1 as a major event in the pathogenesis of JGCTs. The existence of AKT inhibitors currently tested in clinical trials opens new perspectives for targeted therapies for these tumors, which are currently treated with standard non-specific chemotherapy protocols. PMID- 26137585 TI - MET Suppresses Epithelial VEGFR2 via Intracrine VEGF-induced Endoplasmic Reticulum-associated Degradation. AB - Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) drive cancer through their respective receptors, MET and VEGF receptor 2 (VEGFR2). VEGFR2 inhibits MET by promoting MET dephosphorylation. However, whether MET conversely regulates VEGFR2 remains unknown. Here we show that MET suppresses VEGFR2 protein by inducing its endoplasmic-reticulum-associated degradation (ERAD), via intracrine VEGF action. HGF-MET signaling in epithelial cancer cells promoted VEGF biosynthesis through PI3-kinase. In turn, VEGF and VEGFR2 associated within the ER, activating inositol-requiring enzyme 1alpha, and thereby facilitating ERAD-mediated depletion of VEGFR2. MET disruption upregulated VEGFR2, inducing compensatory tumor growth via VEGFR2 and MEK. However, concurrent disruption of MET and either VEGF or MEK circumvented this, enabling more profound tumor inhibition. Our findings uncover unique cross regulation between MET and VEGFR2-two RTKs that play significant roles in tumor malignancy. Furthermore, these results suggest rational combinatorial strategies for targeting RTK signaling pathways more effectively, which has potentially important implications for cancer therapy. PMID- 26137587 TI - P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study. AB - BACKGROUND: Silencing of P16 through methylation and locus deletion is the most frequent early events in carcinogenesis. The aim of this study is to prospectively determine if early P16 methylation is a predictor for oral cancer development. METHODS: Patients (n = 181) with mild or moderate oral epithelial dysplasia (OED) were recruited into the double blind multicentre cohort. P16 methylation was analyzed using the MethyLight assay. Progression of OEDs was monitored for a minimum 3 year follow-up period. FINDINGS: P16 methylation informative cases (n = 152) were enrolled in the prospective multicenter cohorts with an ultimate compliance of 96.7%. OED-derived squamous cell carcinomas were observed in 21 patients (14.3%) during the follow-up (median, 41.0 months). The cancer progression rate from the P16 methylation-positive patients was significantly increased when compared to P16 methylation-negative patients [27.1% vs 8.1%; adjusted odds ratio = 4.6; P = 0.006]. When the P16 methylation-positive criteria were used as a biomarker for early prediction of cancer development from OEDs, sensitivity and specificity of 62% and 76% were obtained, respectively. INTERPRETATION: P16 methylation is unequivocally a marker for determining the malignant potential of OED and there is no need for further research regarding this aspect. FUNDING: National Basic Research Programs of China (2011CB504201 and 2015CB553902), Beijing Science and Technology Commission (Z090507017709016), and Beijing Municipal Administration of Hospital (XM201303) to Dajun Deng. The funding agencies have no role in the actual experimental design, patient recruitment, data collection, analysis, interpretation, or writing of this manuscript. PMID- 26137588 TI - An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis. METHODS: Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing protein antigens of the candidate TAAs. Analyses were done by using receiver operating characteristics (ROC) to calculate diagnostic accuracy. FINDINGS: Twenty-two candidate TAAs were assessed by protein microarray analysis in 914 participants with serum alpha-fetoprotein (AFP) available. Twelve candidate TAAs were statistically different in signal intensity between HCC and controls. Among them, CENPF, HSP60 and IMP-2 showed AUC (area under the curve) values of 0.826, 0.764 and 0.796 respectively for early HCC. The highest prevalence of autoantibody positivity was observed in HCC cases with BCLC tumor stage A, well-differentiated histology and Child-Pugh grade C. Specifically, 73.6% or 79.3% cases of early HCC with negative AFP were positive for autoantibody to CENPF or HSP60. INTERPRETATION: Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC. PMID- 26137589 TI - Mitochondrial-dependent Autoimmunity in Membranous Nephropathy of IgG4-related Disease. AB - The pathophysiology of glomerular lesions of membranous nephropathy (MN), including seldom-reported IgG4-related disease, is still elusive. Unlike in idiopathic MN where IgG4 prevails, in this patient IgG3 was predominant in glomerular deposits in the absence of circulating anti-phospholipase A2 receptor antibodies, suggesting a distinct pathologic process. Here we documented that IgG4 retrieved from the serum of our propositus reacted against carbonic anhydrase II (CAII) at the podocyte surface. In patient's biopsy, glomerular CAII staining increased and co-localized with subepithelial IgG4 deposits along the capillary walls. Patient's IgG4 caused a drop in cell pH followed by mitochondrial dysfunction, excessive ROS production and cytoskeletal reorganization in cultured podocytes. These events promoted mitochondrial superoxide-dismutase-2 (SOD2) externalization on the plasma membrane, becoming recognizable by complement-binding IgG3 anti-SOD2. Among patients with IgG4 related disease only sera of those with IgG4 anti-CAII antibodies caused low intracellular pH and mitochondrial alterations underlying SOD2 externalization. Circulating IgG4 anti-CAII can cause podocyte injury through processes of intracellular acidification, mitochondrial oxidative stress and neoantigen induction in patients with IgG4 related disease. The onset of MN in a subset of patients could be due to IgG4 antibodies recognizing CAII with consequent exposure of mitochondrial neoantigen in the context of multifactorial pathogenesis of disease. PMID- 26137592 TI - An Efficient Approach for Web Indexing of Big Data through Hyperlinks in Web Crawling. AB - Web Crawling has acquired tremendous significance in recent times and it is aptly associated with the substantial development of the World Wide Web. Web Search Engines face new challenges due to the availability of vast amounts of web documents, thus making the retrieved results less applicable to the analysers. However, recently, Web Crawling solely focuses on obtaining the links of the corresponding documents. Today, there exist various algorithms and software which are used to crawl links from the web which has to be further processed for future use, thereby increasing the overload of the analyser. This paper concentrates on crawling the links and retrieving all information associated with them to facilitate easy processing for other uses. In this paper, firstly the links are crawled from the specified uniform resource locator (URL) using a modified version of Depth First Search Algorithm which allows for complete hierarchical scanning of corresponding web links. The links are then accessed via the source code and its metadata such as title, keywords, and description are extracted. This content is very essential for any type of analyser work to be carried on the Big Data obtained as a result of Web Crawling. PMID- 26137590 TI - Allogeneic Mesenchymal Stem Cells Restore Endothelial Function in Heart Failure by Stimulating Endothelial Progenitor Cells. AB - BACKGROUND: Endothelial dysfunction, characterized by diminished endothelial progenitor cell (EPC) function and flow-mediated vasodilation (FMD), is a clinically significant feature of heart failure (HF). Mesenchymal stem cells (MSCs), which have pro-angiogenic properties, have the potential to restore endothelial function. Accordingly, we tested the hypothesis that MSCs increase EPC function and restore flow-mediated vasodilation (FMD). METHODS: Idiopathic dilated and ischemic cardiomyopathy patients were randomly assigned to receive autologous (n = 7) or allogeneic (n = 15) MSCs. We assessed EPC-colony forming units (EPC-CFUs), FMD, and circulating levels of vascular endothelial growth factor (VEGF) in patients before and three months after MSC transendocardial injection (n = 22) and in healthy controls (n = 10). FINDINGS: EPC-colony forming units (CFUs) were markedly reduced in HF compared to healthy controls (4 +/- 3 vs. 25 +/- 16 CFUs, P < 0.0001). Similarly, FMD% was impaired in HF (5.6 +/- 3.2% vs. 9.0 +/- 3.3%, P = 0.01). Allogeneic, but not autologous, MSCs improved endothelial function three months after treatment (Delta10 +/- 5 vs. Delta1 +/- 3 CFUs, P = 0.0067; Delta3.7 +/- 3% vs. Delta-0.46 +/- 3% FMD, P = 0.005). Patients who received allogeneic MSCs had a reduction in serum VEGF levels three months after treatment, while patients who received autologous MSCs had an increase (P = 0.0012), and these changes correlated with the change in EPC-CFUs (P < 0.0001). Lastly, human umbilical vein endothelial cells (HUVECs) with impaired vasculogenesis due to pharmacologic nitric oxide synthase inhibition, were rescued by allogeneic MSC conditioned medium (P = 0.006). INTERPRETATION: These findings reveal a novel mechanism whereby allogeneic, but not autologous, MSC administration results in the proliferation of functional EPCs and improvement in vascular reactivity, which in turn restores endothelial function towards normal in patients with HF. These findings have significant clinical and biological implications for the use of MSCs in HF and other disorders associated with endothelial dysfunction. PMID- 26137591 TI - Predictors of a Good Outcome after Endovascular Stroke Treatment with Stent Retrievers. AB - BACKGROUND AND PURPOSE: Successful recanalization after endovascular stroke therapy (EVT) did not translate into a good clinical outcome in randomized trials. The goal of the study was to identify the predictors of a good outcome after mechanical thrombectomy with stent retrievers. METHODS: A retrospective analysis of a prospectively collected database included consecutive patients treated with stent retrievers. We evaluated the influence of risk factors for stroke, baseline NIHSS score, Alberta Stroke Program Early CT (ASPECT) score, recanalization rate, onset-to-recanalization and onset-to-groin puncture time, and glucose levels at admission on good outcomes. The number of stent passes during procedure and symptomatic hemorrhage rate were also recorded. A modified Rankin Scale (mRS) score of 0-2 at 90 days was considered as a good outcome. RESULTS: From January 2011 to 2014, 70 consecutive patients with an acute ischemic stroke underwent EVT with stent retrievers. The absence of a medical history of diabetes was associated with good outcomes. Apart from diabetes, the baseline demographic and clinical characteristics of patients were similar between subjects with poor outcome versus those with good outcomes. Median time from onset to recanalization was significantly shorter in patients with good outcomes 245 (IQR: 216-313 min) compared with poor outcome patients (315 (IQR: 240-360 min); P = 0.023). Symptomatic intracranial hemorrhage was observed in eight (21.6%) of 37 patients with poor outcomes and no symptomatic hemorrhage was seen in patients with good outcomes (P = 0.006). In multivariate stepwise logistic regression analysis, a favorable ASPECT score (ASPECT > 7) and successful recanalization after EVT were predictors of good outcomes. Every 10 year increase was associated with a 3.60-fold decrease in the probability of a good outcome at 3 months. The probability of a good outcome decreases by 1.43 fold for each 20 mg/dL increase in the blood glucose at admission. CONCLUSION: To achieve a good outcome after EVT with stent retrievers, quick and complete recanalization and better strategies for patient selection are warranted. We need randomized trials to identify the significance of tight blood glucose control in clinical outcome during or after EVT. PMID- 26137593 TI - An Autopsy of Nanofiltration Membrane Used for Landfill Leachate Treatment. AB - Komurcuoda leachate treatment plant, Istanbul, which consists of membrane bioreactor (MBR) and nanofiltration (NF) system, faced rapid flux decline in membranes after 3-year successful operation. To compensate rapid flux decline in membranes, the fouled membranes were renewed but replacement of the membranes did not solve the problem. To find the reasons and make a comprehensive analysis, membrane autopsy was performed. Visual and physical inspection of the modules and some instrumental analysis were conducted for membrane autopsy. Membranes were found severely fouled with organic and inorganic foulants. Main foulant was iron which was deposited on surface. The main reason was found to be the changing of aerator type of MBR. When surface aerators were exchanged with bottom diffusers which led to increasing of dissolved oxygen (DO) level of the basin, iron particles were oxidized and they converted into particulate insoluble form. It was thought that probably this insoluble form of the iron particles was the main cause of decreased membrane performance. After the diagnosis, a new pretreatment alternative including a new iron antiscalant was suggested and system performance has been recovered. PMID- 26137594 TI - Comment on "Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis". PMID- 26137596 TI - Blood B Cell and Regulatory Subset Content in Multiple Sclerosis Patients. AB - OBJECTIVE: B cell targeted therapies have been effective in slowing multiple sclerosis (MS) disease progression suggesting a direct causal link for this lymphoid subset. A small subset of B cells with regulative properties (Bregs) exists in peripheral blood, and induction of Bregs ameliorates experimental autoimmune encephalomyelitis (EAE), the murine model for MS. Therefore the frequency of B cell subsets and regulatory B cells in particular in peripheral blood of MS patients is of interest. METHODS: The phenotype and frequency of B cell subsets in peripheral blood from 32 MS patients and 34 healthy controls (HC) were examined using flow cytometry. RESULTS: We found that there is an increase in CD19+ cell number in MS 1347 +/- 159 cells/MUL, (average +/- SEM) compared to HC, 935 +/- 129 cells/MUL and no apparent deficiency in B-cells with a regulatory phenotype. In addition, we observed a loss of correlation between CD19+ B cells and total lymphocyte count in MS. CONCLUSION: These findings suggest altered blood B-cell homeostasis in MS patients. PMID- 26137595 TI - Multiparameter Flow Cytometric Assays to Quantify Effector and Regulatory T-Cell Function in Multiple Sclerosis. AB - The immune system plays a major pathological and regulatory role in multiple sclerosis (MS) and, therefore, is a focus of extensive research. Animal models of MS have been crucial in understanding the pathological processes in MS and developing certain treatments, however, all crucial aspects of the human disease may not be appropriately modeled. With the exception of detecting oligoclonal bands and IgG synthesis in cerebrospinal fluids of MS patients, there has not been major progress in the development of immunologic tests that can be used for diagnosis of MS. Further, due to the lack of validated immune assays, routine monitoring of the immune system following therapy initiation is not a part of standard patient care in MS. This is critical since immunomodulatory therapies used for MS treatment are not benign and, more importantly, there is a considerable variation in clinical responses in MS patients initiating such therapies. Flow cytometry is a powerful tool that can be used for studying both the phenotype and function of immune cells. The studies described here will demonstrate how flow cytometry can be used to apply current knowledge about the MS immune system to develop a diagnostic laboratory test for the immunologic monitoring of this disease. Importantly, we will also show that the multiparameter flow cytometry based assay developed by us can also be implemented for the immunologic evaluation of therapeutic success in MS patients. PMID- 26137597 TI - Antibiotic resistance linked to corruption. PMID- 26137598 TI - Re: The Animal Protection Index. PMID- 26137599 TI - Government veterinarians in short supply. PMID- 26137600 TI - [Not Available]. PMID- 26137601 TI - [In Process Citation]. PMID- 26137602 TI - [In Process Citation]. PMID- 26137603 TI - [In Process Citation]. PMID- 26137604 TI - In a Heartbeat. PMID- 26137605 TI - How to Win the Battle of the Bugs. You don't need harsh chemicals to keep the biters at bay. We reveal new, safer options. PMID- 26137606 TI - 5 Things You Must Know About Sunscreen. There are more than 1,000 products on the shelves. Here, 15 terrific nonyucky, nonsticky, no-burn options. PMID- 26137607 TI - Regulating compounding pharmacies. AB - (1) The Pew Charitable Trusts identified 27 compounding incidents that resulted in 89 deaths since 2001. (2) Unlike drug manufacturers, compounding pharmacies are generally not required to report adverse events associated with their products to the FDA. (3) Federal law on drug compounding was updated in 2013 to create a new group of compounders called "outsourcing facilities." Over 50 facilities in 23 states are now registered with the FDA. PMID- 26137608 TI - Keeping recreational water facilities safe. AB - (1) Outbreaks of diseases associated with aquatic venues have nearly quadrupled to more than 40 per year. (2) The Cryptosporidium (Crypto) germ is the leading cause of diarrheal outbreaks related to swimming pools. (3) A national voluntary effort is underway to reduce the number of illnesses and injuries from recreational water facilities. PMID- 26137609 TI - [Effect of different dietary fat intake on blood lipids, body fat, adiponectin and leptin on energy balance status in rats]. AB - OBJECTIVE: To investigate the effects of different dietary fat intake on body fat, adiponectin and leptin on energy balance status in rats. METHODS: Forty male SD rats were randomly assigned to four groups. Rats in low fat, normal fat, medium fat and high fat group were fed equal energy diets of low fat diet (5% energy from fat), normal diet (15% energy from fat), medium fat diet (25% energy from fat) and high fat diet (40% energy from fat) respectively. Blood glucose and lipids were analyzed at 0, 5 and 10 weeks. The level of serum adiponectin and leptin was tested at 0 and 10 weeks. At the end of 10 weeks, the rats were sacrificed, the perirenal and periepididymis fat were separated and weighed. The mRNA of adiponectin and leptin in fat tissues were determined by realtime PCR. RESULTS: After the 5 and 10 weeks, the levels of serum triglyceride of rats in medium fat group and high fat group were lower than those in low fat group and normal fat group. At the end of 10 weeks, the expression of adiponectin mRNA in fat tissues in medium fat group was lower than those in low fat group. There were no significant differences among four groups in body fat, blood glucose, blood cholesterol, serum adiponectin and leptin, and the expression of leptin mRNA in fat tissues. CONCLUSION: In energy balance status, different dietary fat intake had no effects on body fat, blood glucose, blood cholesterol, serum adiponectin and leptin in rats. PMID- 26137610 TI - [Research of aluminum to the cognitive ability and genome-wide methylation in rats]. AB - OBJECTIVE: To investigate the effects of aluminum exposure on cognition ability and genome-wide methylation in rats. METHODS: Seventy-two healthy SD male rats were randomly assigned by weight into two parts and nine groups (eight rats/group). Exposure part included control group and low, medium and high dose aluminum maltolate group (0.27, 0.54 and 1.08 mg/kg alumium maltolate). Intervention part included control group, 1.08 mg/kg aluminum maltolate group, 1.08 mg/kg aluminum maltolate and low,medium and high dose folic acid group (0.7, 1.5 and. 3.4 mg/kg folic acid). Aluminum maltolate were subjected to peritoneal injection (0.2 ml/d) and folic acid were subjected to intragastric administration in 1 ml/100 g for 60 days. The learning and memory abilities were examined by using Morris water maze test and genome-wide methylation was determined via ELISA assay. RESULTS: It was revealed by Morris water maze test that target quadrant residence time and through the original position were markedly shortened as a result of medium and high dose aluminum exposure when compared with control group (both P < 0.05). The target quadrant residence time and through the original position were extended as a result of folic acid intervention when compared with 1.08 mg/kg aluminum maltolate exposure group. Both of them had statistical difference between 1.08 mg/kg aluminum maltolate and (1.5 mg/kg and 3.4 mg/kg) folic acid intervention group and 1.08 mg/kg aluminum maltolate exposure group (both P < 0.05). Considerable decrease in genome-wide methylation rate was associated with elevated dosage of aluminum maltolate (0.54 mg/kg and 1.08 mg/kg) as compared with control group (both P < 0.05). The genome-wide methylation rate was gradually increase as a result of high-dose folic acid intervention when compared with high-dose aluminum maltolate exposure group (both P < 0.05). Both of them had no statistical difference when compared with control group (both P > 0.05). CONCLUSION: Aluminum may induce learning and memory abilities and decrease genome-wide methylation rate in rats. Folic acid supplementation may improve its effect. PMID- 26137611 TI - [Testicular oxidative stress and downregulation of CYP17a1 indused by di (n butyl) phthalate inhibit synthesis of testosterone]. AB - OBJECTIVE: To explore the relationship and possible mechanisms between testicular oxidative injury caused by DBP and the testosterone synthesis pathway. METHODS: Twenty-four male Wistar male rats (4-wk-old) were randomly divided into 4 groups, three doses of DBP (80, 200 and 500 mg/kg) groups and a vehicle (corn oil) control group, 6 animals each. The rats were respectively administered by gavage once a day for four weeks. They were sacrificed after 4 weeks treatment and the body weights, testis, epididymis were weighed, respectively. The oxidation of MDA and ROS, the activity changes of antioxidases SOD, CAT and GPx-1, as well as the activities of steroid synthetases 3beta-HSD1, 17beta-HSD3 in the testis homogenate were measured by biochemical methods. The levels of testosterone, LH, FSH in peripheral blood and testosterone, ASD in testis were measured by radioimmunoassay. The intensities of expresses of StAR, P450scc, 3beta-HSD1, 17beta-HSD3 and CYP17a1 mRNA were detected by real-time qPCR. RESULTS: In 500 mg/kg dose group, the body weights and weigths of testis were decreased obviously (P < 0.05). The concentration of serum LH and FSH was increased, the consentration of serum T, testicular T and testicular ASD was decreased (P < 0.05). The oxidation of MDA and ROS was increased distinctly and the activities of SOD, CAT, GPx-1 and 3beta-HSD1 were reduced (P < 0.05). StAR, P450scc, 3beta HSD1 and CYP17a1 mRNA were decreased, 17beta-HSD3 mRNA was increased (P < 0.05). In 200 mg/kg dose groups, LH, FSH level in peripheral blood were increased and ASD level in testis was decreased (P < 0.05). The oxidation of ROS was increased and activity of GPx-1 and 3beta- HSD1 were decreased (P < 0.05). StAR, P450scc and CYP17a1 mRNA were decreased (P < 0.05). There were no changes in 80 mg/kg group. CONCLUSION: DBP exposure disturbed the balances of oxidation/antioxidation, then result in the decline of GPx-1 activity, CYP17a1 mRNA and ASD level which caused the decrease of testosterone synthesis in leydig cell. It is speculated that the decrease of CYP17a1 may be one of the mechanisms of toxic effects of DBP. PMID- 26137612 TI - [Course and risk factors of maternal pregnancy-related anxiety across pregnancy in Ma' anshan city]. AB - OBJECTIVE: To explore the prevalence, trends and related influencing factors of pregnancy-related anxiety throughout pregnancy. METHODS: A total of 990 pregnant women at the maternal and child health centers of Ma' anshan participated in all three surveys. Data on demographic characteristic and exposure factors during pregnancy were collected. The Pregnancy-related Anxiety Questionnaire was used to assess the anxiety symptoms. Generalized estimating equations (GEE) was used to evaluate the related influencing factors of pregnancy-related anxiety. RESULTS: The mean score of the pregnancy-related anxiety were 20.3 +/- 4.9, 19.6 +/- 4.6, 18.9 +/- 4.4 for the first, second and third trimester, respectively. Pregnancy related anxiety showed a significant difference among the three trimesters ( F = 63.10, P < 0.001). Prevalence of pregnancy-related anxiety were 21.0%, 17.7% and 13.6%, respectively, at the first, second and third trimester. Results from GEE analysis indicated that maternal education of senior high school( OR = 1.36, 95% CI 1.05 - 1.75), lower family monthly income (OR =1.33, 95%, CI 1.01 - 1.75), unplanned pregnancy (OR = 2.60, 95% CI 2.05 - 3.29), history of miscarriage (OR = 1.30, 95% CI 1.06 - 1.60), vaginal bleeding (OR = 1.61, 95% CI 1.22 - 2.12), fever ( OR = 1.69, 95% CI 1.17 - 2.46) and use of nutritional supplementation during pregnancy ( OR = 1.43, 95% CI 1.08 - 1. 88 ) significantly increased the risk of pregnancy-related anxiety. CONCLUSION: Pregnancy-related anxiety appeared a decrease from the first to third trimester. Maternal education, economic situation, unplanned pregnancy, history of miscarriage, and adverse physiological symptoms such as vaginal bleeding and fever were associated with the risk of pregnancy-related anxiety. PMID- 26137613 TI - [Relationship between dietary pattern during late pregnancy and fatty acid composition of transitional milk in inland regions of China]. AB - OBJECTIVE: To investigate dietary pattern during late pregnancy and fatty acid composition of transitional milk in inland regions of China. METHODS: Eighty Chinese women were recruited from two different geographical inland regions (Jurong, an inland region close to freshwater. Xushui, an inland region with limited access to freshwater, forty women from each region) during late pregnancy. Their dietary status during late pregnancy was recorded and fatty acid composition in transitional milk was quantified. RESULTS: Both marine fish consumption frequencies during late pregnancy were less than one time/week. The consumption of rapeseed oil in Jurong was significantly higher than in Xushui (P < 0.05). The total lipids contents of Jurong and Xushui were (4.39 +/- 1.18) g/100g and (3.92 +/- 1.47) g/100g, respectively (P = 0.11), and DHA composition were (0.46 +/- 0.20 )% and (0.29 +/- 0.09 )%, respectively (P < 0.05). There was positive relationship between rapeseed oil consumption and DHA in transitional milk (r = 0.362, P < 0.05). CONCLUSION: Fatty acid composition in transitional milk differed between these two inland regions of China, which may be caused by difference of maternal dietary pattern during late pregnancy. The intake of precursor of n-3 long chain polyunsaturated fatty acid could compensate its dietary deficiency to some extent. PMID- 26137614 TI - [Analysis of antimicrobial resistance results of Vibrio parahaemolyticus isolated from shellfish and its habitat in 2013]. AB - OBJECTIVE: To evaluate the antimicrobial resistance of Vibrio parahaemolyticus isolated from shellfish and its habitat in Sichuan, Fujian and Guangxi. METHODS: The susceptibility of 186 isolates of Vibrio parahaemolyticus to 8 antibiotics were determined by broth microdilution susceptibility test. The antibiotics of ampicillin, cefotaxime, ceftazidime, gentamicin, tetracycline, chloramphenicol, ciprofloxacin and trimethoprim/sulfamethoxazole were used. RESULTS: The antibiotic resistance rate were 69.35% in which ampicillin resistance was the most prevalent. The geometric mean of ampicillin MIC value of all isolates was greater than the interpretation value of resistance. Among the 186 tested isolates, the multiple antibiotic resistance and/or intermediate resistance was 4. All strains were 100% sensitive to cefotaxime, ceftazidime, chloramphenicol and ciprofloxacin. The ampicillin susceptibility spectrum of aquaculture farm was the highest among the three sectors as 73.68% and Sichuan was the highest among the three provinces as 70.94% although there were no significant differences. There were 44 samples out of which 2 and above strains were isolated, and the susceptibility spectrum polymorphism rate of strains isolated from the same sample was 77.27% (34/44). CONCLUSION: The ampicillin resistance rate is relatively high, and shellfish habitat may be the main source of antimicrobial resistance of Vibrio parahaemolyticus. There is an urgent need to strengthen the surveillance and management of Vibrio parahaemolyticus in the shellfish breeding process. PMID- 26137615 TI - [Study on the relationship between WBC count levels and type 2 diabetes mellitus in Hui and Han nationality of Ningxia]. AB - OBJECTIVE: To analyze the relationship between WBC count levels and type 2 diabetes mellitus in Hui and Han nationality of Ningxia. METHODS: Using the method of case-control study, people of regional organizations and institutions aged 20 - 60 who received medical health checkup and endocrine patients in General Hospital of Ningxia Medical College and WuZhong city People's Hospital from October 2011 to October 2012 were enrolled in the study. According to the inclusion and exclusion criteria of T2DM patients and control groups, with gender, ethnic and age are not more than 3 years old cases and controls of matching, the T2DM group (case group) of 351 cases and non-T2DM group (control group) of 655 cases were determined. These subjects underwent questionnaire investigation, understand first, like the situation, the way of life, disease and medication history, family history. Physical examination: including height, weight, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), and according to the height and weight to calculate body mass index (BMI), and laboratory tests, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), low density lipoprotein (LDL-C), blood uric acid (UA ), nmda aminotransferase ( AST) , alanine aminotransferase (ALT), blood biochemical indexes. Results Diabetes group of average age (50.28 + 8.32), 194 patients with male, (55.27%), 157 patients with female (44.73%) and control group in average age (50. 17 + 7. 14) , including 337 men (51.45% ) and 318 women (48.55%). Average age, gender, the proportion between the two groups had no statistical significance of difference. The white blood cell value of T2DM group (6.66 x 10(9) +/- 1.61 x 10(9)/L) was higher than that of non-T2DM group (6.11 x 10(9) +/- 1.49 x 10(9)/L), there was a significant difference (t = -5.430, P < 0.01); Comparing the mean value of white blood cell of Hui (6.459 x 10(9) +/- 1.45 x 10(9)/L) and Han nationality (6.169 x 10(9) +/- 1.63 x 10(9)/L), there was a significant difference (P < 0.05). T2DM group, the abnormal level of white blood cell was 2.6%, that of non-T2DM group was 0.8%, The T2DM group was significantly higher than that of non-T2DM group (chi2 = 4.168, P = 0.041). Comparing the abnormal level of white blood cell of Hui and Han nationality, there was no significant difference. After adjustment for age, gender, nation, TG, TC, HDL, LDL, ALT, AST and blood glucose, the odds ratios for T2MD were 4.072 in the people with the WBC abnormal people and the WBC normal people. After adjustment for age, gender sick or not, TG, TC, HDL, LDL, ALT, AST and blood glucose, the odds ratios for WBC increased were 1. 582 in the people with the Hui and Han nationality. CONCLUSION: The WBC count levels are closely associated with type 2 diabetes, and with the increase of the level, the association enhanced gradually, the WBC may be involved in the occurrence and development of type 2 diabetes. there is a certain relationship between ethnic genetic factors and the WBC count level. PMID- 26137616 TI - [Influence of removing iodized salt on children's goiter status in areas with high iodine in drinking water]. AB - OBJECTIVE: To explore the changes of goiter prevalence of children living in areas with high iodine in drinking water after removing iodized salt from their diet. METHODS: Three towns with median water iodine of 150 - 300 MUg/L were selected randomly in Hengshui city of Hebei province of China. A total of 452 and 459 children in the 3 towns were randomly selected to measure thyroid volume by ultrasound before and after removing iodized salt, respectively. Their goiter status was judged using the criteria of age-specific thyroid volume recommended by the WHO. RESULTS: After removing iodized salt, the overall goiter prevalence in the three towns significantly decreased from 24.56% (111/452) to 5.88% (27/459) (P < 0.01). The goiter prevalence in 8, 9 and 10 year-old children decreased respectively from 33.70% (31/92), 23.32% (45/193) and 20.96% (35/167) to 6.10% (10/164), 5.52% (9/163) and 6.06% (8/132). The goiter prevalence in boys and girls decreased from 27.05% (66/244) and 21.63% (45/208 ) to 6.66% (15/226 ) and 5.15% (12/233), respectively. The decreases in children's goiter prevalence across gender and age group were all significant. CONCLUSION: Children's goiter prevalence decreased significantly after removing iodized salt from their diet for about one and half years in the HIA in Hebei province. PMID- 26137617 TI - [Status of exercise and sedentary activities in the leisure time among third and fourth grade pupils in three cities of Shandong province]. AB - OBJECTIVE: To analyze the status and the influence factors of exercise and sedentary activities in the leisure time among third and fourth grade pupils in Qingdao, Tai' an and Yantai city of Shandong province. METHODS: With random cluster sampling, a total of 2283 primary students were selected from three cities of Shandong province. Questionnaires were used to collect the information on their exercise, sedentary activities. RESULTS: In the past week the participation rate of exercise in the leisure time among the pupils was 65.9%. Among the pupils who participated exercise, the average days of moderate and high intensity exercise was four, and the average daily exercise time was 30 minutes. The average time of sedentary activities in the leisure time was 0.9 h/d, and the rate of 2 hours and over per day of sedentary activities was 13.6%. Pupils participating the exercise was related to their area, gender, their satisfaction of their body image and their parents' exercise. Their sedentary patterns was related to their understanding of their own body weight and their parents' sedentary behavior. CONCLUSION: Intervention related to physical activity should be strengthened among pupils and their parents to promote their physical activity level. PMID- 26137618 TI - [Maternal iron overload results in liver damage in rat offspring]. AB - OBJECTIVE: To investigate the effects of iron overload on the liver tissue and function of maternal rats' offspring. METHODS: Forty pregnant rats were randomly divided into four groups, high-dose group, middle-dose group, low-dose group (120, 60 and 30 mg/kg BW) and control group. Iron detran was administered by intraperitoneal injection every other day and the entire trial lasted for 6 weeks. After 6 weeks, the iron serum levels, GOT and GPT of rats' offspring were determined. Histological changes of the liver injury were measured. The expressions of Bcl-2 and Bax in liver were measured by immunohistochemistry method. In addition, MDA, SOD and GSH-Px in liver were assessed by spectrophotometry. RESULTS: After 6 weeks, the level of serum iron in control group was significantly lower than in middle-dose and high-dose group (P < 0.05), and the result of level of liver iron was similar with that. According to the HE staining, it showed that liver cell gradually was damaged with the increasing of accumulation of hepatic iron. The expression of Bcl-2/Bax was significantly higher in control group than in middle-dose and high-dose groups (P < 0.05). The levels of serum GPT and GOT in high-dose group were significantly higher in control group (P < 0.05). The levels of Liver MDA in middle-dose and high-dose groups were both significantly higher than in control group (P < 0.05). Moreover, the levels of liver GSH-Px and SOD in high-dose group were significantly lower than in control group (P < 0.05). CONCLUSION: Iron overload in maternal rats may result in excessive iron deposition and oxidative damage of liver tissue and cell function in maternal rats' offspring. PMID- 26137619 TI - [Effects of dietary wheat gluten level on decreasing plasma homocysteine concentration in rats]. AB - OBJECTIVE: To investigate the effects of different level of casein and wheat gluten on decreasing plasma homocysteine concentration in rats. METHODS: 48 rats of the Wistar were fed with different level of casein (12.5%, 25% and 50%) and wheat gluten (14.5%, 29% and 58%) diets for 14 days, and they were killed by decapitation to obtain blood and livers was subject to analysis the concentration of homocysteine, cysteine and other amino acids, as well as BHMT and CBS activities. RESULTS: Body weight gain in rats fed wheat gluten dietary was significantly less than casein dietary, but food intake was significantly decreased in wheat gluten group with increasing of the protein content. The plasma homocysteine concentration in rats fed wheat gluten was marketly less than casein, however plasma cysteine concentration in wheat gluten was higher than casein group. CONCLUSION: The effects of wheat gluten on plasma homocysteine concentration are mainly depends on the low contents of methionine and high cysteine content, but the low contents of lyscine and threonine are not ignored. The mainly mechanism is that the increased cysteine concentration promot enzyme activities of homocystein metabolism, and increase the consumption of homocysteine. PMID- 26137620 TI - [Inhibition of antisense VEGF gene on the growth of glioma cells BT325]. AB - OBJECTIVE: To investigate the inhibitory effect of antisense VEGF gene on growth of human glioma BT325 and induced apoptosis in cells. METHODS: The pcDNA3.1/anti VEGF eukaryotic expression vector was constructed and transfected into human glioma BT325. The ELISA assay was used to assess the expression of VEGF gene. Soft agar colony formation, MTT assay and electron microscope were used to evaluate the proliferation, apoptosis and the morphological changes of BT325. RESULTS: Compared with a control group, the level of VEGF expression was significantly decreased and was almost completely suppressed. The amount in soft agar colony at vector group and antisense VEGF gene group were 21 and 2, respectively. The growth of BT325 was significantly inhibited to 38.23% and resulted in the apoptotic morphology by antisense VEGF gene under electron microscope, compared to vector group. CONCLUSION: Antisense VEGF gene inhibited the growth and proliferation, induced cell apoptosis, played an efficient role of anti-cancer in BT325 cells. PMID- 26137621 TI - [Association between polymorphisms in the human dopamine D3 receptor gene and genetic susceptibility of essential tremor]. AB - OBJECTIVE: To study the association between polymorphisms in the human dopamine D3 receptor ( DRD3 ) gene and genetic susceptibility of essential tremor in different groups. METHODS: The DRD3 gene polymorphism in ET and health control groups were analyzed with MscI restricted fragment length polymorphism ( RFLP). The results of PCR-RFLP were analyzed by using the statistical software. RESULTS: No significant differences in alleles and allele frequency of MscI site at the DRD3 gene locus were observed between healthy control and different ET groups. CONCLUSION: There is no association between polymorphisms MscI site at DRD3 and genetic susceptibility of ET. PMID- 26137622 TI - [Determination of 14 pesticide residues in honey by ultra high performance liquid chromatography-high resolution mass spectrometry]. AB - OBJECTIVE: To establish a method for simultaneous determination of 14 pesticide residues in honey by ultra high performance liquid chromatography-high resolution mass spectrometry ( UPLC-HRMS). METHODS: Honey samples were extracted with 1% formic acid in acetonitrile, and the extracts were cleaned up with dispersive solid phase extraction (d-SPE ) using the mixture of PSA and C18 powder as sorbents. The extract components were separated on an Accucore aQ C18 column (2.6 MUm, 2.1 mm x 150 mm) by gradient elution. The qualitative and quantitative analyses were operated under Full Scan/ddms2 mode by high resolution mass spectrometry. RESULTS: The response of each pesticides showed a good linearity with the correlation coefficient not less than 0.998. The limits of quantitation ( LOQs, S/N >= 10) for the 14 pesticides in honey were from 0.6 to 6 MUg/kg. The recovery results with spike blank honey samples at the levels of LOQs, 15 and 30 MUg/kg were satisfied with average recovery rates of 80.3% -112.7% and the RSDs of 0.4% -7.1%. CONCLUSION: The proposed method was suitable for the rapid screening and quantitative analysis of pesticide residues in honey. PMID- 26137623 TI - [Determination of four bisphenolic compounds in drinking water by liquid chromatography-tandem mass spectrometry]. AB - OBJECTIVE: To simultaneously determine the four bisphenolic compounds (bisphenol F, bisphenol A, tetrachlorobisphenol A and tetrabromobisphenol A) in drinking water by liquid chromatography tandem mass spectrometry. METHODS: 200 ml water sample was extracted by solid-phase extraction, eluted with methanol and analyzed by liquid chromatography tandem mass spectrometry under the MRM mode. The separation was carried out on a T3 column (2.1 mm x 150 mm, 3 MUm). RESULTS: The limits of detection for the four bisphenolic compounds were in the range of 0.20 5.5 ng/L. The mean recoveries at the two spiked levels were 87.1% - 109.0% with the intra-day precision between 6.3% - 12.4% and inter-day precision between 4.5% - 15.4%. The method was applied for determination of 15 water samples. CONCLUSION: The method was sensitive, precise and accurate. PMID- 26137624 TI - [Determination of dimethyl fumarate in bakery food by d-SPE-HPLC-PDA]. AB - OBJECTIVE: To establish a simple and rapid pretreatment method with dispersive solid phase extraction ( d-SPE) by HPLC for determination of dimethyl fumarate in bakery foods. METHODS: Dimethyl fumarate in samples was ultrasonically extracted by methanol, and cleaned up with d-SPE. Then, it was separated on C18 chromatographic column (4.6 mm x 25 mm, 5 MUm) with a mixture of methanol--0.03 mol/L sodium acetate and 0.008 mol/L tetrabutyl ammonium bromide (40: 60, V/V) as mobile phase. The photodiode array detector was used in the determination under lambda = 220 nm. RESULTS: In the linear range of 0.1 -25 MUg/ml, the correlation coefficients was r > 0.999, and the average recoveries of the spiked samples were in the range of 82.8% - 107.5% with relative standard deviations (RSD) in the range of 3.30% - 7.30% (n = 6). The limit of detection ( LOD) was 0.4 mg/kg, and the limit of quantification was 1.0 mg/kg. CONCLUSION: The method is simple, rapid, sensitive and accurate, and suitable for determine dimethyl fumarate in bakery foods. PMID- 26137625 TI - [Comparison for ELISA and CLIA of serum 25-hydroxy vitamin D determination]. AB - OBJECTIVE: To estimate the bias between the enzyme linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CLIA) of serum 25-hydroxy vitamin D (25 (OH) D) determination, and to evaluate the correspondence of two methods. METHODS: Forty human serum samples were collected, and the serum 25 (OH) D were determined by immunodiagnostic systems 25-hydroxy vitamin D EIA and immunodiagnostic systems iSYS analyser. According to the standards of NCCLS EP9 A2 files, the within and without outlier, test adequate range, used linear regression procedure, and compare average and maximum bias between these two methods were excluded. RESULTS: In the linear regression analysis, the results of the two methods were correlated, y = 0.995x + 2.3928, r = 0.981. The relative standard deviation between these two methods was smaller with the higher serum 25(OH) D levels. CONCLUSION: The correlation and repeatability of serum 25 (OH) D determination by ELISA and CLIA are fine. PMID- 26137626 TI - [Study on factors influencing DNA sequencing by automatic genetic analyzer]. AB - OBJECTIVE: To acquire accurate and successful DNA sequencing in a cost-effective way by ABI3500xl automatic genetic analyzer. METHODS: BigDye was diluted to 8, 16 and 32 times in PCR product sequencing. Three different methods including CENTRI SEP kit, BigDye cleaning beads and ethanol-NaAc-EDTA were used to purify the sequencing PCR products. RESULTS: The results of DNA sequencing were correct when BigDye was diluted up to 16 times. The misreading of nucleic acid bases was found as BigDye was diluted to 32 times. All three purification methods provided acceptable DNA sequencing results. In terms of method for purification of PCR products, the CENTRI-SEP Kit was the most expensive but time-saving (0.5 h), while ethanol-NaAc-EDTA method was the most economical but time-consuming (2 h). The BigDye cleaning beads method was of a suitable purification time (1 h) but not fit for high-throughput DNA sequencing. CONCLUSION: BigDye should be diluted up to 16 times in DNA sequencing by ABI3500xl DNA analyzer. Although all three purification methods may promise DNA sequencing results with good quality, it is necessary to choose an appropriate one to keep the balance between time and cost on the basis of the lab condition. PMID- 26137627 TI - [Research on olaquindox induced endoplasmic reticulum stress related apoptosis on nephrotoxicity]. AB - OBJECTIVE: Renal tubular epithelial cell were exposed to olaquindox and detected the ROS and apoptosis related proteins, to investigate the renal tubular epithelial cell apoptosis through endoplasmic reticulum stress mediated pathway induced by olaquindox. METHODS: MTT assay (1, 2, 3, 4, 5, 6, 7and 8 MUmol/ml olaquindox exposure) was used to detect the effects of olaquindox on renal tubular epithelial cell proliferation to determine test concentrations. Hoechst 33258 was used to detect morphological changes on apoptotic cells in each group. Flow cytometry method was applied to detect the apoptosis rate and intracellular reactive oxygen, and western blot assay was performed to detect the levels of endoplasmic reticulum stress-related apoptosis proteins, GRP78, GRP94 and CHOP. RESULTS: According to results of the MTT test, 1, 2, 3 and 4 MUmol/ml olaquindox concentrations were determined for apoptosis analysis. With the increase of olaquindox concentration, apoptosis rate and levels of endoplasmic reticulum stress related apoptosis pathway protein GRP78, GRP94 and CHOP increased, levels of ROS were increased in every groups (P < 0.05) in 2 MUmol/ml olaquindox groups and above. With the prolongation of olaquindox exposure, apoptosis rate and levels of endoplasmic reticulum stress related apoptosis pathway protein GRP78 and GRP94 increased in 12 and 24 h olaquindox exposure groups, whereas in groups of olaquindox exposed for 6, 12 and 24 h, levels of ROS and endoplasmic reticulum stress related apoptosis pathway protein CHOP increased (P < 0.05). CONCLUSION: Olaquindox can induce renal tubular epithelial cells to apoptosis and cause the renal toxicity, and the endoplasmic reticulum stress-related apoptosis maybe the associated toxicity pathway. PMID- 26137628 TI - [Effect of PM2.5 on oxidative stress-JAK/STAT signaling pathway of human bronchial epithelial cells]. AB - OBJECTIVE: To investigate the regulation of oxidative stress-JAK/STAT signaling pathway on cytokines in human bronchial epithelial cells induced by PM2.5. METHODS: Bronchial epithelial cells 16HBE were cultured using traditional invasive methods. Two aspects were explored, one is the relationship among PM2.5, oxidative stress, JAK/STAT signaling pathway. There were the following groups, control group, N-acetyl-L-cysteine (NAC, 5 mmol/L) group, 50 MUg/ml PM2.5 group, 100 MUg/ml PM2.5 group, 50 MUg/ml PM2.5 + 5 mmol/L NAC group, 100 MUg/ml PM2.5 + 5 mmol/L NAC group. Intracellular ROS levels and the gene expression of JAK2 and STAT3 were detected after all groups were exposed for 24 h. The other one is to explore the relationship among PM2.5, JAK/STAT signaling pathway and cytokine. The groups were arranged the following, control group, 6 MUmol/L AG490 group, 100 MUg/ml PM2.5 group, 6 MUmol/L AG490 + 100 MUg/ml PM2.5 group. The level of IL-6 was determined after all groups were exposed for 24h. RESULTS: After 24 h exposure, intracellular ROS levels and the gene expression of JAK2 and STAT3 in 50 MUg/ml PM2.5, 100 MUg/ml PM2.5 exposure group were higher than the control group. Intracellular ROS levels and the gene expression of JAK2 and STAT3 in PM2.5 + NAC protection group were lower than the respective PM2.5 exposure group, the differences were statistically significant (P < 0.05). IL-6 levels of cellular supernatant in 6 MUmol/L AG490 + 100 MUg/ml PM2.5 group were lower than 100 MUg/M PM2. group, the differences were statistically significant ( P < 0.05). CONCLUSION: PM2.5 could cause oxidative damage on bronchial epithelial cells, and then regulate JAK/STAT signaling pathway and relative cytokines of epithelial cells through oxidative stress. PMID- 26137629 TI - [Dynamic changes of ROS, MDA and SOD during arsenic-induced neoplastic transformation in human keratinocytes]. AB - OBJECTIVE: To investigate the level of ROS, MDA and SOD in different stages of arsenic-induced neoplastic transformation in human keratinocytes. METHODS: HaCaT human immortalized keratinocytes were continuously exposed to 1.0 MUmol/L arsenite for 35 passages. The secretion of active MMP-9, the proliferation rate and doubling time nd colony formation assay in soft agar colony were used to identify the malignant phenotype of the arsenite-exposed HaCaT cells. Then flow cytometry was used to detect the levels of ROS, and the level of MDA and SOD were tested by biochemical method at different passages of arsenite exposure in HaCaT cells. RESULTS: A marked increase in the secretion of active MMP-9 in the arsenic treated (1.0 MUmol/L NaAsO2) cells was observed in comparison to the passage matched untreated control (0.0 MUmol/L NaAsO2) cells at 28 and 35 passages. And compared with 0.0 MUmol/L NaAsO2 group, the proliferation rate and doubling time in 1.0 MUmol/L NaAsO2 group was much faster at 21 ((64.37 +/- 15.92) h) and 28 ((64.04 +/- 12.84) h) passages with a significant statistical difference at passage 35 ((54.00 +/- 2.35 ) h) (P < 0.05). Furthermore, the long-term arsenite treated cells formed significantly higher colonies (107 +/- 11 in passage 35) in soft agar than control cells (P < 0.05). No obvious regularity changes of ROS and MDA levels were found before 14 passages of arsenite exposure, except for passage 1. Surprisingly, after 14 passages, with the increased passages of exposure to arsenite, both the ROS and MDA levels decreased gradually, the ROS level at passage 35 was significant lower compared to passage 0 (P < 0.05). Conversely, after passage 21, the activity of SOD was obviously enhanced and reached the highest level at passage 35. CONCLUSION: Long-term exposure to low concentrations of inorganic arsenic-induced malignant transformation of HaCaT cells is accompanied by intracellular imbalance between oxidative-antioxidant, which increased expression of SOD and low levels of ROS found in the later-stage of arsenite-induced transformation. PMID- 26137630 TI - [Allelopathic inhibitory effects on Microcystis aeruginosa of two species of allium plants]. AB - OBJECTIVE: To research the algal inhibiting effects of two species of allium plants chives and leeks to provide theoretical basis and application for biological control of cyanobacterial blooms. METHODS: The inhibitory effects of different concentrations of leeks and chives (chives stem leaf and roots respectively) water extracts on M. aeruginosa were studied. RESULTS: The three kinds of water extracts from leek, chives stem leaf and chives roots respectively all had distinct inhibitory effects on M. aeruginosa, and their inhibitory ratios of lowest concentration group (5%, V/V) were 60.8%, 65.0%, 97.8%, respectively. Compared with the control group, the densities of M. aeruginosa in all experiment groups were lower than the control groups in the same period, and the inhibitory effect were more obvious with the increase of the water extract concentrations. Among them, chives roots water extracts had the best inhibitory effect on M. aeruginosa, to the fifth day, M. aeruginosa almost completely dead of the lowest concentration (5%, V/V) and the EC50 was 2.28 g/L fresh weight. CONCLUSION: Chives roots water extracts have a very good algal inhibiting effect, which can be developed an efficient and ecological security algistat. PMID- 26137631 TI - [A quantitative risk assessment model of salmonella on carcass in poultry slaughterhouse]. AB - OBJECTIVE: To construct a quantitative risk assessment model of salmonella on carcass in poultry slaughterhouse and to find out effective interventions to reduce salmonella contamination. METHODS: We constructed a modular process risk model (MPRM) from evisceration to chilling in Excel Sheet using the data of the process parameters in poultry and the Salmomella concentration surveillance of Jinan in 2012. The MPRM was simulated by @ risk software. RESULTS: The concentration of salmonella on carcass after chilling was 1.96MPN/g which was calculated by model. The sensitive analysis indicated that the correlation coefficient of the concentration of salmonella after defeathering and in chilling pool were 0.84 and 0.34,which were the primary factors to the concentration of salmonella on carcass after chilling. CONCLUSION: The study provided a quantitative assessment model structure for salmonella on carcass in poultry slaughterhouse. The risk manager could control the contamination of salmonella on carcass after chilling by reducing the concentration of salmonella after defeathering and in chilling pool. PMID- 26137632 TI - [Effects of fructose on triglycerides in individuals with diabetes: a Meta analysis of experimental trials]. AB - OBJECTIVE: To assess the effects of fructose on the blood triglycerides, particularly examining treatment dose, duration, and control of food in individuals with diabetes. METHODS: A systematic review and Meta-analysis of experimental clinical trials were conducted to investigate the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol. MedLine, EMBASE, The Cochrane Library, CMBdisc, CNKI (1970-2014), and some related journals were searched. Heterogeneity was assessed by 2 tests and quantified by I2. Meta-analysis was conducted by RevMan 5.3. RESULTS: 15 reports (21 trials) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides under specific conditions in individuals with type 2 diabetes. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the dose was >= 100 g fructose/d (WMD 0.17, 95% CI0.08 - 0.25, P < 0.0001). A triglyceride-raising effect with heterogeneity was seen in type 2 diabetes when the reference carbohydrate was starch (WMD 0.13, 95% CI 0.02 - 0.23 , P = 0.02). CONCLUSION: Effect of fructose on the level of TG in type 2 diabetes patients is more sensitive than that in type 1 diabetes. The effect on triglycerides is dose dependent and depends on what kinds of carbohydrate is being exchanged with fructose. PMID- 26137633 TI - [Metagenomics as a Tool for the Investigation of Uncultured Microorganisms]. AB - Uncultured microorganisms represent a significant part of the Earth's biodiversity. Natural ecosystems contain less than 0.1-1% of the microorganisms that can be cultured in the laboratory. Therefore, new methodological approaches are required for the identification and description of uncultured microorganisms, for studies of their genetic diversity and the structure of microbial associations, and for an understanding of their ecological importance in the biosphere. Metagenomics, a method of analyzing the collective genome.of a microbial community without cultivation, makes it possible to unravel fundamental matters of the microbiology and ecology of microorganisms. Another efficient method of analysis of uncultured forms of microorganisms is "single cell genomics," which involves the isolation of single cells from microbial communities and the sequencing of their genomes. Developed in the last decade, the high throughput technologies of next-generation sequencing provide important input into the investigation of genome reconstruction for all of the microorganisms residing and interacting within ecosystems. This review describes the major methodological approaches used in metagenomic analysis of microbial communities, as well as accomplishments in the search for new uncultured microorganism, the unraveling of their genomes, and an elucidation of their role in ecosystems. PMID- 26137634 TI - [The bithorax Complex of Drosophila melanogaster as a Model for Studying Specific Long-Distance Interactions between Enhancers and Promoters]. AB - In higher eukaryotes regulation of the expression of genes responsible for the development of the organism is a complex process. Often, a single gene may be regulated in different cells and time intervals with the help of dozens of enhancers and promoters. It has recently become clear that enhancers directly interact with target promoters, and the intervening chromatin loops out. However, the mechanisms that ensure the specificity of long-distance interactions between enhancers and promoters remain unclear. One of the most convenient models for the study of remote interactions between the regulatory elements is the bithorax complex (BX-C) of Drosophila melanogaster. This review describes the regulation of the expression of the BX-C homeotic genes and discusses the existing models that explain the specificity of remote interactions between the enhancers and promoters at this locus. PMID- 26137635 TI - [Transcription Factors in Developmental Genetics and the Evolution of Higher Plants]. AB - Transcription factors play an essential role in controlling various developmental programs in plants, coordinating the action of any genetic network. Among the most important groups of plant transcription factors are the homeodomain containing transcription factors, in particular, those belonging to the KNOX and WOX families, the functions of which are associated with regulation of the meristem activity, development of the aboveground and underground parts of plants, and control of embryogenesis. This review examines the role of KNOX and WOX transcription factors in various developmental programs, as well as in the evolutionary complication of the body plan in terrestrial plants. PMID- 26137636 TI - [Virus-Induced Silencing as a Method for Studying Gene Functions in Higher Plants]. AB - The method of virus-induced gene silencing (VIGS) based on posttranscriptional gene silencing (PTGS) is a promising new method for the study of plant gene functions. In the current review we analyzed works on the development and improvement of this method, including the creation of new viral constructions for different plant species, the search for new reporter genes for the control of VIGS efficiency, and the development of new efficient methods of infection. PMID- 26137637 TI - [Genetics and Genomics of Wheat: Storage Proteins, Ecological Plasticity, and Immunity]. AB - Recent advances in genetics and genetic research methods made it possible to explain the large polymorphism observed among storage proteins of wheat weevil (gliadins and glutenins), to determine their genetic control mechanism, and to develop a system for the identification of wheat genotypes on the basis of multiple allelism. This system has extremely high sensitivity and efficiency, which makes it possible to conduct studies to determine the purity and authenticity of wheat varieties, the dynamics of alleles diversity in time and space, the phylogenetics, etc., through the use of an extensive database on the allelic composition of gliadin loci. An investigation of the molecular structure of genes controlling the synthesis of storage proteins and their organization on chromosomes, as well as an analysis of wheat genome structure, revealed the molecular mechanisms of variability in the wheat genome and its reorganization in response to changes in environmental conditions and cultivation technologies. The multilevel genetic system of protection against pathogens and adverse environmental factors that developed in the course of wheat evolution continues to astound researchers' imagination with new resistance genes and novel types of antimicrobial peptides having been discovered and sequenced in recent years and the diversity of their structures and mechanisms of action in response to pathogens. An analysis of gene sequences involved in wheat domestication, namely, those that define ecological plasticity, i. e. the type of plant development (Vrn genes), and those responsible for spikelet traits (Q genes), which ensured the successful cultivation of wheat by humans, revealed that the basis for these features are specific mutations. PMID- 26137638 TI - [Genetic History of Salmonid Fishes of the Genus Oncorhynchus]. AB - This review discusses genetic approaches to solving important problems of evolutionary biology of salmonid fishes with special reference to Pacific salmon and trout. The problems of the genetic phylogeny of salmonid fishes, including issues of the consistency/inconsistency of phylogenetic tree topologies built using genetic and phenotypic characteristics, the timing of the main phylogenetic events, the relationships among different taxa, including the mutual status of Pacific salmon and trout, and others are discussed. The problems of the tetraploidization of the salmonid fishes, as well as,the dilemma of their freshwater/marine origin, and the semelparity of some of the species are reviewed. PMID- 26137639 TI - [Molecular Genetic Markers of Economically Important Traits in Dairy Cattle]. AB - The selection efficiency of complex quantitative economically important traits in dairy cattle depends on the identification of candidate genes responsible for these traits, as well as the determination of causative DNA polymorphism in these genes. Here, we review examples of DNA polymorphisms in coding and noncoding parts of genes that are associated with milk yield, milk fat and protein contents, milk fat and protein percentages, the biochemical composition of milk, and other milk production traits. Together with data with of foreign authors, which were obtained predominantly for Holstein animals, much attention in the review is paid to domestic studies on Russian cattle breeds. Particular attention is dedicated to DNA polymorphisms in the genes encoding transcription factors, which can potentially affect a large number of traits. The results of association analyses are summarized in a table, and they present the progress of research in this area in recent years. Our analysis indicates that the majority of SNPs, which are associated with significant effects on milk production traits, are in fact in a linkage disequilibrium with yet unknown mutations. The identification of functionally significant DNA polymorphisms and other genetic factors (epimutations, VNTR) is necessary for effective marker-assisted selection and genomic selection of diary cattle breeds. PMID- 26137640 TI - [Neurogenetics and Neuroepigenetics]. AB - "Genetics of behavior," or "Neurogenetics," is based on the evolutionary ideas of T. Dobzhansky on brain development and behavior. It continues with the "experimental genetics of higher nervous activity" of I. Pavlov and uses a comparative approach in the study of heredity and variation in behavioral manifestations, from Protozoa to humans. The study of the classical Pavlovian conditioned reflex in mutant Drosophila helped to identify the main types of memory and their evolutionary conservatism. Long-term memory defects are caused by mutations of the same genes as in mental, retardation in humans, when signaling cascades intersecting with the cAMP-dependent pathway are damaged. The cascade of actin remodeling is also among these. The key enzyme, LIM-kinase 1, controls cognitive manifestations of the "genomic disease" Williams deletion syndrome. Its study resulted in the recognition of neuroepigenetics as an interface between the genome and environmental influences. Epigenetic factors of "variability"--DNA methylation, histone acetylation, and microRNA regulation--do not change the structure of the gene but its manifestations. Certain miRNAs have already been considered to be both biomarkers for neurodegenerative diseases and factors of the intergenerational transmission of the behaviorial properties of ancestors who experienced stress from adverse environmental influences. PMID- 26137641 TI - [Philo of Alexandria and his views on health and sickness]. AB - Philo of Alexandria, Torah scholar and philosopher of religion, (c. 20 BC to 50 BCE) is the first Middle Platonic philosopher whom we know through his own works. His thinking was determined by the two antitheses of God and world, and virtue and vice. The Logos (divine reason) mediates between the transcendent God and the earthly world. His thoughts on health and illness and on the possibilities and limitations of medicine are testimony to his comprehensive philosophical education as well as to his belief in God as ruler of the world and of human life. He saw human health as the reward for self-control for which one was best prepared by the classical education programme. Self-control and physical exercise were therefore, in his view, possible guarantors of health, and a coach potentially more important than a physician. Illnesses, if they result from the loss of self-control, may point to the necessity for penitence. Philo therefore saw virtuousness as the safest precondition for a healthy and cheerful life. That the life forces increase during youth and diminish in old age is part of destiny. Similarly, illness can be brought about by strokes of fate. If illness occurred in this or any other way, medicine was there to help and its success or failure depended on divine providence. Like Jesus Sirach, the Jewish scholar who taught around a hundred years earlier, Philo did not think it sinful to use medical help if one was ill, seeing that God himself had made natural remedies available. He compared the importance of physicians for their patients to that other professionals have in people's lives. Philo did not provide a compendium on the work of the physician, but he gave indications, on nutrition for instance, or on the use of laxatives and fragrances, or that complaints can be necessary stages of recovery. Philo also asked himself whether physicians were always obliged to tell patients the truth. The only case of illness he described in sufficient detail was one of leprosy, which he diagnosed in accordance with Leviticus 13:2. Philo saw physicians as helpers of God, who was the Lord of life and who would therefore decide on the fate of the healthy and sick. Faith in God, Philo thought, was vital if one was to cope with life's ups and downs. Only the wicked had to fear death, however, while the souls of the righteous returned to heaven after death. PMID- 26137642 TI - [Love on enemy territory: Belgrade, Cetinje and Lublin under Austro-Hungarian occupation in World War I]. AB - During World War I, Serbia and Montenegro were under Austro-Hungarian occupation between late 1915/early 1916 and 1918. This article explores the attitude of the occupiers towards prostitution and venereal disease, among the indigenous population as well as among their own soldiers, officers and female support staff. The measures taken were primarily guided by military considerations. For the military, the occupied areas were zones that served particular purposes, such as preserving peace and order behind the front, making use of manpower and resources, and serving as cordon sanitaire. In spite of this, pseudo-peace-like structures evolved in the capitals Belgrade and Cetinje that facilitated the spread of prostitution and venereal disease. In my article, I will look at the scale of the debate and of the proposed countermeasures. It is noticeable that women were usually branded as the perpetrators, while the soldiers were seen as the ones in need of protection. In spite of this, it is apparent how candidly the royal-imperial army dealt with the topic even though it went against the current ideas of morality. The social differentiation that was customary in the imperial and royal army applied here, too. Officers suffering from venereal disease had their own hospitals and brothels and were permitted leave more often (a fact that went against the purpose of these institutions). The topic also received publicity because the military physicians, who were in fact civilians mobilized by the army, chose to publish continuously on the topic. Based on the microcosm of occupied enemy territory, my contribution shows how ideas of morality changed during the war despite traditional gender stereotypes, and the role played by the military in these developments. PMID- 26137643 TI - [Protestant healthcare? The building of denominational hospitals in Berlin during the Weimar Republic]. AB - This essay tries to show that, in the Berlin of the Weimar Republic, Protestant hospitals were built not only to relieve the suffering of the population, but also out of a sense of inferiority to a reinvigorated Catholicism. Hospitals were consequently not only places of care and healing but also of denominational self assertion. Based on Olaf Blaschke's thesis of a "second denominational age," this contribution tries to demonstrate that the responsible Protestant agents did not make anti-Catholic proclamations at every occasion and in all the media. The founders of the "Protestant Hospital Building Association," which this essay investigates, made deliberate use of anti-Catholic resentment, expressing it boldly when approaching the Protestant elites, while playing it down deliberately when addressing the people of Berlin. With a view to the severe economic crisis and mass unemployment prevailing from 1930, they justified the building of new hospitals with the need to create work places, without making recourse to the denomination argument. The political situation, the addressees and the hope for economic success seem to have informed the representation of denominational resentments decisively. Confessionalism therefore seemed to have been not as much a question of ideology as one of strategy. PMID- 26137644 TI - [Medicine for the elderly or science of old age? Max Burger's contribution to geriatric medicine and gerontology]. AB - The fact that, due to demographic changes, gerontology and geriatrics are gaining ever more importance gives rise to more questions regarding the history of the science of aging. Based on unpublished sources and relevant publications by Max Burger, the doyen of gerontological research in Germany, our contributions trace the beginnings of age research in Germany. Our results confirm Burger as the dominant expert in this field in the first decades of its emergence. Burger was primarily interested in basic medical-scientific research, and less in clinical geriatrics. His scientific goal was not to establish a medicine for the elderly but a theory of life changes ("biomorphosis"). From the start, he saw aging as a physiological process--a view that is still valid today. His concept of "biomorphosis", however, did not catch on and reveals a constriction in Burger's thinking, which was to some extent influenced by Hans Driesch's vitalism. Interdisciplinary approaches are noticeable in the natural sciences rather than the humanities or social sciences. Burger's research was also influenced by the political system he lived in. During National Socialism, which Burger joined--at least formally--in 1937, his research into labour economics and aging met with considerable interest in connection with the general mobilisation of resources. East Germany also had an interest in questions of labour productivity in old age and the extension of the working life, which meant that Burger remained a sought after physician and scientist up into the 1960s. As he grew older himself, Burger's initially deficit-oriented view of old age gave way to a more positive presentation that attached greater weight to the resources of old age. PMID- 26137645 TI - [The development of nursing schools in East and West Germany]. AB - This study compares the various nursing schools in East and West Germany. In the 1980s and early 1990s the professionalization of nursing was still in its infancy there compared with Anglo-America. There were attempts to professionalize nursing that were meant to enhance the quality of nursing as well as lead to improved working conditions. As part of the political debates in the field after German reunification, the nursing schools in the former east were also affected by reform efforts. From the 1960s, diploma courses in nursing studies and in the teaching of medicine had been offered in the east and, up into the 1990s, these courses were repeatedly modified and adapted to educational requirements. The study also tries to establish the extent to which the academization of nursing in the reunified Germany was driven by the concurrence of the different training routes in West and East. It analyses above all the diverse study syllabi and lengths of training. What also emerged was that, despite all the positive impulses arising from the East German training models, the continuous changes in training in the GDR not only served to improve the nursing qualifications but also to promote identification with the socialist system and its political ideology. In addition, the teaching of theory was never prominent in East German nursing, while, in the west, theory was increasingly asked for and eventually also implemented. The possibility, in the former east, to study the teaching of medicine definitely made an impact on the nursing training in the west after the reunification and the subject is now offered at universities there, too. Despite all that, the concept of "professional nursing," which needs to be practised in a practical, patient-oriented way, and on a scientific basis, is again being discussed since the introduction of Bachelor and Master study courses. The process of professionalizing and academizing the nursing schools and further training courses clearly continues despite the impulses received from the former East Germany. PMID- 26137646 TI - [Nosode and sarcode therapies and their history--a controversial inheritance]. AB - Nosodes and sarcodes (homeopathic remedies gained primarily from disease products respectively organs of human or animal origin) are groups of drugs which were added to the homeopathic Materia Medica in the 1830s. Most substances used in nosode or sarcode therapy have a long medical tradition, with some even going back to the pre-Christian period. My contribution first describes therapeutic practices that use these substances and then juxtaposes them with their use in the early days of homeopathic nosode and sarcode therapy. The investigation shows, on the one hand, that there are aspects common to both approaches that go far beyond the mere choice of substances. On the other hand, it demonstrates the effect the inclusion of human or animal body substances in the homeopathic Materia Medica has had on homeopathy, as their use is no longer in line with what is considered rational. PMID- 26137647 TI - [How to dose correctly? An overview of debates in the United States, Great Britain and Germany (1830s to 1970s)]. AB - The dispute over low and high potencies is no longer current in today's homeopathy, but from the 1830s to the 1960s it played a major role in scientific discourse. The devotees of high potencies claimed to be the only true Hahnemannians, while their antagonists tried to practise a scientific, modernized homeopathy. The former ultimately triumphed in Britain, the U.S. and Germany, but this happened on quite different routes in each of these countries. As well as Hahnemann, other scholars, such as Constantin Hering, James T. Kent and Karl Koetschau, played important roles in the international disputes. PMID- 26137648 TI - ["A change in medical thinking?" or "over-eager literary activity?" August Bier, homeopathy and the Nobel Prize 1906-1936]. AB - This essay explains the nomination and evaluation procedure for the Nobel Prize for Physiology or Medicine. Its research is based on original files and on the example of August Karl Gustav Bier (1861-1949). It discusses the minutes of the Nobel Committee for physiology or medicine, which are kept in the Nobel Archives, as well as the unusually high number of nominations of August Bier and the nominations submitted by him; it also describes the reasons why August Bier, in the end, never received the Nobel Prize. The essay focuses mainly on the reception of Bier's homeopathic theses by the Nobel Prize Committee and his nominators. PMID- 26137649 TI - [Advertising and Zeitgeist. The advertising of Schwabe Pharmaceuticals]. AB - This contribution explores the advertisements for homeopathic products in magazines in the first half of the twentieth century, focusing on the period between 1933 and 1945 and based on the example of the pharmaceutical company Dr Willmar Schwabe. In the first half of the twentieth century, Schwabe Pharmaceuticals was market leader for homeopathic and other complementary medical products (phytotherapy, biochemicals). The example chosen as well as the time frame complement the existing research. We searched three German publications (the homeopathy journal Leipziger Populare Zeitschrift fur Homoopathie, the medical weekly Munchner Medizinische Wochenschrift and the pharma magazine Pharmazeutische Zeitung) and collected target-group-specific results for laypersons, physicians and pharmacists. Analysis of the images and texts in the selected advertisements often reflected the historical background and the respective health policies (wartime requirements, times of need, "Neue Deutsche Heilkunde"). The history of this traditional company was seen as an important point in advertising, as were the recognisability of the brand through the company logo, the emphasis on the high quality of their products and the reference to the company's own research activities. We furthermore found the kind of argumentation that is typical of natural medicine (naturalness, the power of the sun, prominent representatives). Schwabe met the expectations of its clients, who were interested in complementary medicine, whilst pursuing an approach to homeopathy that was compatible with natural science, and it presented itself as a modern, scientifically oriented enterprise. The company did not lose credibility as a result, but increased its clientele by expanding to include the whole naturopathic market. PMID- 26137650 TI - Lessons to be Learned from Recent Biosafety Incidents in the United States. AB - During recent months, the Centers for Disease Control and Prevention (CDC) announced the occurrence of three major biosafety incidents, raising serious concern about biosafety and biosecurity guideline implementation in the most prestigious agencies in the United States: the CDC, the National Institutes of Health (NIH) and the Federal Drug Administration (FDA). These lapses included: a) the mishandling of Bacillus anthracis spores potentially exposing dozens of employees to anthrax; b) the shipment of low pathogenic influenza virus unknowingly cross-contaminated with a highly pathogenic strain; and c) an inventory lapse of hundreds of samples of biological agents, including six vials of variola virus kept in a cold storage room for decades, unnoticed. In this review we present the published data on these events, report the CDC inquiry's main findings, and discuss the key lessons to be learnt to ensure safer scientific practice in biomedical and microbiological service and research laboratories. PMID- 26137651 TI - Video Surveillance in Mental Health Facilities: Is it Ethical? AB - Video surveillance is a tool for managing safety and security within public spaces. In mental health facilities, the major benefit of video surveillance is that it enables 24 hour monitoring of patients, which has the potential to reduce violent and aggressive behavior. The major disadvantage is that such observation is by nature intrusive. It diminishes privacy, a factor of huge importance for psychiatric inpatients. Thus, an ongoing debate has developed following the increasing use of cameras in this setting. This article presents the experience of a medium-large academic state hospital that uses video surveillance, and explores the various ethical and administrative aspects of video surveillance in mental health facilities. PMID- 26137652 TI - Prognostic Value of Glycated Hemoglobin for One Year Mortality Following Hospitalization in the Internal Medicine Ward. AB - BACKGROUND: The impact of admission glycated hemoglobin (HbA1c) on hospital outcome is controversial. OBJECTIVES: To evaluate the association between admission glucose and HbA1c levels and mortality 1 year after hospitalization in the internal medicine ward. METHODS: HbA1c level of consecutive patients was measured during the first 24 hours of admission to the internal medicine ward and divided at the cutoff point of 6.5%. Three groups of patients were prospectively identified: patients with preexisting diabetes mellitus (DM), patients with glucose > 140 mg/dl (hyperglycemia) on admission and no known diabetes (H), and patients without diabetes or hyperglycemia (NDM). The primary end-point was 1 year all-cause mortality. RESULTS: A total of 1024 patients were enrolled, 592 (57.8%) belonged to the DM group, 119 (11.6/6) to the H group and 313 (30.6%) to the NDM group. At 1 year, death occurred in 70 (11.9%) in the DM group, 12 (10.0%) in the H group and 15 (4.8%) in the NDM group (P = 0.002). Elevated admission glucose levels did not influence outcome in any of the groups. HbA1c levels were similar for survivors and non-survivors (P = 0.60). Within-group multivariate analysis adjusted for comorbidities and age showed that in the H group HbA1C levels of 6.5% or above were associated with increased mortality risk [hazard ratio (HR) 8.25, 95% confidence interval (CI) 1.93-35.21]. In the DM group, HbA1c levels below 6.5% were associated with increased mortality risk (HR = 2.05, 95% CI 1.25-3.36). CONCLUSIONS: Glucose levels upon admission did not affect mortality. However, HbA1c levels below 6.5% had opposite effects on 1 year mortality in diabetes patients and patients with hyperglycemia. PMID- 26137653 TI - Waterpipe Tobacco Smoking in Three Israeli Adult Populations. AB - BACKGROUND: Waterpipe tobacco smoking (WTS) is common in some populations and may add increased risk for tobacco-related diseases. OBJECTIVES: To assess the rates of WTS and risk practices associated with WTS in three distinct populations in Israel: long-term Jewish residents (LTJR), immigrants from the former Soviet Union (fSU), and Arabs. METHODS: We conducted a cross-sectional survey of 899 randomly selected participants, age 30-65 years, using face-to-face interviews with subjects from the three population groups in Israel. Respondents reported WTS, cigarette smoking, alcohol consumption, and socioeconomic characteristics. RESULTS: Among men, WTS at least once a week was reported by 4.8% of LTJR, 3.2% of fSU immigrants and 20.3% of Arabs. Lower rates were reported among women of all groups. The younger, less educated men and the younger unmarried women had higher odds of WTS. LTJR who smoked cigarettes and drank alcohol had higher odds of WTS [odds ratio (OR) 32.6, confidence interval (CI) 9.36-113.6; OR = 3.57, CI = 1.48-8.63, respectively], compared to non-smokers and non-drinkers. fSU immigrants who smoked cigarettes had higher odds of WTS (OR = 3.40, CI = 0.99 11.7) compared to non-smokers. Among Arabs, cigarette smoking and alcohol consumption were not associated with WTS. CONCLUSIONS: Arabs are more likely than other Israeli populations to engage in WTS. This behavior may add to increased inequalities in rates of tobacco-induced diseases between Arabs and Jews in Israel. Including WTS in the policies for smoke-free public places is called for. PMID- 26137654 TI - Association of Vitamin B12 Deficiency with Homozygosity of the TT MTHFR C677T Genotype, Hyperhomocysteinemia, and Endothelial Cell Dysfunction. AB - BACKGROUND: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations. OBJECTIVES: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype. METHODS: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes. RESULTS: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 +/- 16 MUM among TT homozygotes as compared to 12.3 +/- 5.6 MUM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal ( 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%). CONCLUSIONS: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency be tested for MTHFR polymorphism in order to identify potential vascular abnormalities and increased cardiovascular risk. PMID- 26137655 TI - Main Imaging Features of Crohn's Disease: Agreement between MR-Enterography and CT-Enterography. AB - BACKGROUND: Only a few studies have compared the accuracy of magnetic resonance enterography (MRE) and computed tomography enterography (CTE) in the diagnosis of Crohn's disease and its complications. OBJECTIVES: To compare the sensitivity of MRE and CTE analysis in their ability to detect, sign-by-sign, 10 classical imaging signs of Crohn's disease. METHODS: The study group comprised 42 biopsy proven Crohn's disease patients who underwent both CTE and MRE within an average period of 6 weeks. Agreement between the two modalities in detecting the 10 most significant radiological signs of CD was evaluated using the Kappa index. The sensitivity of MRE and CTE was calculated using a standard of reference composed of all the findings seen by CTE and/or MRE. We analyzed MRE and CTE sensitivity separately in two groups, according to the time interval between the examinations. RESULTS: Agreement between CTE and MRE was more than 70% in 8 of the 10 signs: mural thickening, phlegmon, stenosis, skip lesions, mucosal stratification, fistula, abscess, and creeping fat. The Kappa level of agreement values for CTE versus MRE varied between substantial for phlegmon and skip lesions; moderate for fistula, creeping fat, abscess and mural thickening; and fair for stenosis and dilatation. CTE detected more findings than MRE, except for creeping fat and fistula. There was no significant difference in the sensitivity of CTE and MRE in the two groups defined by the time interval (time < 1.5 and time > 1.5 months) except for detection of dilatation. CONCLUSIONS: Almost all imaging signs of Crohn's disease were detected equally well by both modalities regardless of the time interval between examinations. We therefore consider MRE to be reliable for imaging and follow-up in patients with Crohn's disease who may need recurrent imaging. PMID- 26137656 TI - High Degree Atrioventricular Block Complicating Acute Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention: Incidence, Predictors and Outcomes. AB - BACKGROUND: In the era of primary percutaneous coronary intervention (PPCI), information on the incidence and prognostic significance of high degree atrioventricular block (AVB) in ST elevation myocardial infarction (STEMI) patients is limited. OBJECTIVES: To assess the incidence, time of onset, predictors and prognostic significance of high degree AVB in a large cohort of consecutive STEMI patients undergoing PPCI. METHODS: We retrospectively studied 1244 consecutive STEMI patients undergoing PPCI. Patient records were reviewed for the presence of high degree AVB, its time of occurrence and relation to in hospital complications, as well as long-term mortality over a 5 year period. RESULTS: High degree AVB was present in 33 patients (3.0%), in 25 (76%) of whom the conduction disorder occurred prior to PPCI. Twelve patients (36%) required temporary pacing, all prior to or during coronary intervention, and all AVB resolved spontaneously before hospital discharge. AVB was associated with a significantly higher 30 day (15% vs. 2.0%, P = 0.001) and long-term mortality rate (30% vs. 6.0%, P < 0.001). Time of AVB had no effect on mortality. In a multivariate regression model, AVB emerged as an independent predictor for long term mortality (hazard ratio 2.8, 95% confidence interval 1.20-6.44, P = 0.001). CONCLUSIONS: High degree AVB remains a significant prognostic marker in STEMI patients in the PPCI era, albeit transient. PMID- 26137657 TI - Human Herpes Virus-6 Following Pediatric Allogeneic Hematopoietic Stem Cell Transplantation. AB - BACKGROUND: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear. OBJECTIVE: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT. METHODS: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006-June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations. RESULTS: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load. CONCLUSIONS: HHV-6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation. PMID- 26137658 TI - Normal Heart Rate Variability in Colchicine-Resistant Familial Mediterranean Fever Patients. AB - BACKGROUND: The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF. OBJECTIVES: To evaluate ANS function in colchicine non responders by using the HRV tool. METHODS: The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls. RESULTS: No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters. CONCLUSIONS: Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults. PMID- 26137659 TI - Parenteral Nutrition in Very Low Birth Weight Preterm Infants. AB - Parenteral nutrition (PN) must be initiated as soon as possible after delivery in very low birth weight (VLBW) preterm infants in order to prevent postnatal growth failure and improve neurodevelopmental outcome. When administered early, high levels of parenteral amino acids (AA) are well tolerated and prevent negative nitrogen balance. Although proteins are the driving force for growth, protein synthesis is energy-demanding. Intravenous lipid emulsions (ILE) constitute a good energy source because of their high energy density and provide essential fatty acids (FA) along with their long-chain polyunsaturated fatty acid (LC-PUFA) derivatives necessary for central nervous system and retinal development. Early supply of ILE is not associated with increased morbidity. No significant differences were found between ILE based on soybean oil only and mixed ILE containing soybean oil in combination with other fat sources, except for a reduction in the incidence of sepsis with non-pure soybean ILE, and possibly less PN-associated liver disease with mixed ILE containing some fish oil. In preterm infants glucose homeostasis is still immature in the first days of life and abnormalities of glucose homeostasis are common. VLBW infants may not tolerate high levels of glucose infusion without hyperglycemia. Administering lower levels of glucose infusion as part of full early PN seems more successful than insulin at this stage. Postpartum there is a transition period when the water and electrolyte balance may be severely disturbed and should be closely monitored. Avoiding fluid overload is critical for preventing respiratory and other morbidities. PMID- 26137660 TI - Breach of Safety and Security in United States Government Institutions: How it Applies to Israel. PMID- 26137661 TI - Presacral Mass Discovered during Pregnancy followed by Myasthenia Gravis. PMID- 26137662 TI - Unilateral Obstructive Urinothorax Secondary to Colorectal Carcinoma. PMID- 26137663 TI - A Non-Coronary Left Main Obstruction Causing Chest Pain. PMID- 26137665 TI - Longitudinal Melanonychia in an African Patient with Acquired Immunodeficiency Syndrome (AIDS). PMID- 26137664 TI - Cannabinoid Hyperemesis Syndrome: Descriptive Overview of an Under-Recognized Diagnosis. PMID- 26137666 TI - Osler-Weber-Rendu Syndrome. PMID- 26137667 TI - Leaking Aortic Pseudoaneurysm Originating from the Left Main Coronary Artery Anastomosis: CT-Angio image and reality. PMID- 26137668 TI - [European medical materials in Japan: the lessons of Phillipp Franz von Siebold (1796-1866) in Nagasaki]. PMID- 26137669 TI - [Medication: 15 years 'EU-directive orphan drugs']. AB - The article describes the compounding, dispensing and reimbursement of orphan drugs in Belgium 15 years after the implementation of the EU Directive on orphan drugs. Despite the fact that they are life-threatening and free of charge, patient compliance to oral orphan medication seems to be a major problem that needs to be handled by the dispensing pharmacist. Parenteral orphan medication needs to be compounded in the hospital pharmacy following strict guidelines concerning handling and storage. For ultra-rare disorders the medication needs to be compounded using sometimes chemical grade ingredients without any pharmaceutical monograph. Cost-effectiveness will always remain a subject for debate. PMID- 26137670 TI - [Andreas Vesalius: his rich imagination and colorful detail account in his book: 'Research of the anatomical observations of Gabriel Falloppius']. AB - In a long letter, Andreas Vesalius reacts to the comments made by Gabriel Falloppius to his work 'De Humani Corporis Fabrica'. In this letter, he proves Falloppius wrong in a number of assertions and corrects him on more than one occasion. In doing so, Vesalius as a renaissance humanist uses a classic Latin language with long elegant sentences in the style of the old Roman orator Cicero. Remarkably interesting is the fact that this whole argumentation is spiced with comparisons and examples from daily life. To make it clear to the reader what a certain part of the skeleton looks like, he compares this part with an object everybody knows. All parts of the human body are depicted in such an almost graphic way that even an interested reader without any medical or anatomic education can picture them. And Vesalius is very creative in doing so, an artist as it were with a very rich imagination. Moreover, it's remarkable how the famous anatomist manages to put himself on the level of any ordinary person, using comparative images on that level. This last work of Vesalius, which he himself considers to be a supplement to his De Humani Corporis Fabrica, deserves special attention, not only because it illustrates the scientific evolution of the anatomist Vesalius, but also because it offers an insight in the psychology of that fascinating scientist Andreas Vesalius. PMID- 26137671 TI - [Chinmedomics: a new strategy for research of traditional Chinese medicine]. AB - Syndrome and formulae (or prescription) are two key issues in traditional Chinese medicine (TCM) and the premise research for material basis of TCM. However, vagueness of syndromes and complexity of formulae greatly limited the evaluation to syndromes and effective substance basis of prescription. Therefore, how to solve the evaluation of syndromes, confirming the efficacy material basis in prescription are the current hot issues of international concern. To solve these problems, establishing chinmedomics by integrated serum pharmacochemistry of TCM with metabolomics technology, that is a unique method of TCM research, made outstanding contributions in solving international concerns such as the effectiveness and security aspects of TCM. On the basis of the biological characterization of syndrome, the metabolic profiling of animal models of TCM syndrome, and related metabolic fingerprints as well as metabolic biomarkers were established to evaluate the overall effects of TCM formulae and corresponding relationship of syndrome-formulae. The active constituents were screened using the plotting of correlation between (endogenous) marker metabolites and (exogenous) serum constituents (PCMS), and is ongoing verification by further biological experiments. Correlation analysis between the ingredients in the body after oral formulae and endogenous markers in vivo can be used to clarify the active ingredients and synergistic properties. This method was successfully applied for rapid discovery of potentially bioactive components and metabolites from TCM, and through a series of studies on the chinmedomics, it proved that the established method could help to explore the effective substance for further research of TCM. As a new research approach, Chinmedomics is the best method to fit the holistic concept of TCM, and it can not only interpret the essence of syndrome but also elucidate the scientific connotation of Chinese medical formulae. PMID- 26137672 TI - [Advance in studies on effect of Glycyrrhizae Radix et Rhizoma in relieving purgative activity of Rhei Radix et Rhizoma]. AB - Rhei Radix et Rhizoma, as a commonly used traditional Chinese medicine, has been widely applied in clinic. Its major purgative constituent is anthraquinones, which are believed to be a toxic ingredient. Glycyrrhizae Radix et Rhizoma has been reputed as the best alexipharmic to moderate medicine natures. In this paper, the effect of Glycyrrhizae Radix et Rhizoma in relieving purgative activity of Rhei Radix et Rhizoma was studied in two aspects--the boiling process and intestinal metabolism; Studies on combined administration of Glycyrrhizae Radix et Rhizoma and Rhei Radix et Rhizoma in recent years were summarized according to chemical constituent, intestinal flora, I/II phase metabolism and drug transport. However, the material basis and mechanism for their compatibility remain unclear, further studies will be made in the future. PMID- 26137673 TI - [Advance in modern studies on compatibility of Coptidis Rhizoma and Evodiae Fructus]. AB - In traditional clinical application, Coptidis Rhizome and Evodiae Fructus have been combined to treat various stomach heat and cold syndromes, gastritis, gastric ulcer and the like. With the application of modem instruments and the development of molecular pharmacologic theory, their chemical constituents and pharmacological effects have been sufficiently studied. In this paper, literatures from Pubmed were adopted, with particular emphasis on findings of international counterparts and studies on compatibility of main chemical components in Coptidis Rhizoma and Evodiae Fructus, in order to elaborate on the scientific comparability of Coptidis Rhizoma and Evodiae Fructus through chemical analysis, and pharmacological and biopharmaceutics studies and introduce the future development trend of the studies. PMID- 26137674 TI - [Advance in studies on hepatoprotective effect of Salvia miltiorrhiza and its main components]. AB - Dried roots and rhizomes of Salvia miltiorrhiza (Danshen) are among the most commonly used traditional Chinese medicines in clinic. The material basis for its efficacy mainly includes hydrophobic tanshinones and hydrophilic salvianolic acids. The traditional effects of Danshen are "removing stasis and relieving pain, activating blood to promote menstruation, clearing heart fire and tranquilization". According to modern pharmacological studies, Danshen and its main components have cardiovascular and cerebrovascular protective effect. Recent studies showed that Danshen and its main components also demonstrated protective effects on liver injury models induced by carbon tetrachloride, D-galactosamine, acetaminophen and alcohol. In this paper, the hepatoprotective effect and mechanism of Danshen were summarized and studied. PMID- 26137675 TI - [Research progress of genetic engineering on medicinal plants]. AB - The application of genetic engineering technology in modern agriculture shows its outstanding role in dealing with food shortage. Traditional medicinal plant cultivation and collection have also faced with challenges, such as lack of resources, deterioration of environment, germplasm of recession and a series of problems. Genetic engineering can be used to improve the disease resistance, insect resistance, herbicides resistant ability of medicinal plant, also can improve the medicinal plant yield and increase the content of active substances in medicinal plants. Thus, the potent biotechnology can play an important role in protection and large area planting of medicinal plants. In the development of medicinal plant genetic engineering, the safety of transgenic medicinal plants should also be paid attention to. A set of scientific safety evaluation and judgment standard which is suitable for transgenic medicinal plants should be established based on the recognition of the particularity of medicinal plants. PMID- 26137676 TI - [Research status and prospect of primary processing of traditional Chinese medicinal materials]. AB - The primary processing is important links and closely related to the quality of traditional Chinese medicinal materials, and is not only cleaning of remove the non-officinal parts, drying for termination the physiological status of organisms, but also retaining the most active substances, decreasing the toxic components, and promoting the transformation among chemical ingredients through primary processing. So the traditional primary processing endows with characters, quality, specifications and properties of traditional Chinese medicine, and embodies some important science truth. The traditional primary processing method and technology systems are derived from the long-term practices and experiences, which are distinctive, colorful, diverse, and scientific, which are helpful to development and utilization of traditional Chinese medicine resources. This paper systemically expounds the research status of the Chinese medicine processing method, summarizes the problems in the primary processing of traditional Chinese medicinal materials research, and prospects its bright future. PMID- 26137677 TI - [Correlation analysis between meteorological factors, biomass, and active components of Salvia miltiorrhiza in different climatic zones]. AB - In this study, the growth and accumulation of active components of Salvia miltiorrhiza in twenty two experimental sites which crossing through three typical climate zones. The S. miltiorrhiza seedlings with the same genotype were planted in each site in spring, which were cultivated in fields with uniform management during their growing seasons till to harvest. The diterpene ketones (dihydrotanshinone, cryptotanshinone, tanshinone I and tanshinone II(A)) in S. miltiorrhiza root samples were determined by using high-performance liquid chromatography (HPLC) method. The biomass of root (root length, number of root branches, root width and dry weight) was also measured. The results showed that tanshinone II(A) in all samples of each site were higher than the standards required by China Pharmacopoeia. It has been found there is a relationship between root shape and climate change. The correlation analysis between active components and meteorological factors showed that the accumulation of tanshinones were effected by such meteorological factors as average relative humidity from April to October > average vapor pressure from April to October > average temperature difference day and night from April to October > annual average temperature and so on. The correlation analysis between root biomass and meteorological factors exhibited that root shape and accumulation of dry matter were affected by those factors, such as average annual aboveground (0-20 cm) temperature from April to October > annual average temperature > average vapor pressure from April to October > annual active accumulated temperature > annual average temperature > average vapor pressure from April to October. The accumulation of tanshinones and biomass was increased with the decrease of latitude. At the same time, the dry matter and diameter of root decreased if altitude rises. In addition, S. miltiorrhiza required sunlight is not sophisticated, when compared with humid and temperature. To sum up, S. miltiorrhiza can adapt to a variety of climatic conditions and the southern warm humid climate is more conducive to its growth and accumulation of active components. PMID- 26137678 TI - [Isolation and antimicrobial activities of actinomycetes from vermicompost]. AB - In this paper, actinomycetes were isolated from vermicompost by tablet coating method. Antimicrobial activities of actinomycetes were measured by the agar block method. Strains with high activity were identified based on morphology and biochemical characteristics, as well as 16S rDNA gene sequence analysis. The results showed that 26 strains of actinomycetes were isolated, 16 of them had antimicrobial activities to the test strains which accounts for 61.54% of all strains. Among the 16 strains, the strain QYF12 and QYF22 had higher antimicrobial activity to Micrococcus luteus, with a formed inhibition zone of 27 mm and 31 mm, respectively. While the strain QYF26 had higher antimicrobial activity to Bacillus subtilis, and the inhibition zone diameter was 21 mm. Based on the identification of strains with high activity, the strain QYF12 was identified as Streptomyces chartreusis, the strain QYF22 was S. ossamyceticus and the strain QYF26 was S. gancidicus. This study provided a theoretical basis for further separate antibacterial product used for biological control. PMID- 26137679 TI - [Molecular identification of hairy antler by analysis of high resolution melting]. AB - High resolution melting (HRM) , an important technology for genotyping and mutation scanning, has broad prospects in the authenticity of traditional Chinese medicine. This paper selected universal CO I primers and used HRM to establish a new method for authenticity of Hairy Antler. PCR was conducted at the annealing temperature of 60 degrees C and 45 cycles. The range of the DNA template concentration, the primer concentration and the Mg2+ ion concentration were further optimized. The results showed that the Tm values of Cervus nippon were (81.96 +/- 0.07), (84.51 +/- 0.03) degrees C and Cervus elaphus was(82.58 +/- 0.13), (85.95 +/- 0.05) degrees C with 10-100 mg . L(-1) DNA template, 0.2 uLmol . L(-1) primer, 2.0 mmol . L(-1) Mg2+. This method can authenticate of hairy antler and is simple, fast, high-throughput, visualization. PMID- 26137680 TI - [Quality classification criteria of Paeonia suffruticosa seeds]. AB - In order to establish the quality classification criteria of Paeonia suffruticosa seeds, thirty-one batches of P. suffruticosa seeds from different provenances were selected. The seed rooting rate, seed germination rate, seed purity, seed viability, 1,000-seed weight and moisture content were determined and analyzed through SPSS 20.0 software. Seed rooting rate, seed germination rate and seed purity were selected as the main index for classification, while 1,000-seed weight, seed viability and moisture content could be used as important references. The seed quality grading of P. suffruticosa was set as three grades. The seed quality of each grade should meet following requirements: For the first grade seeds, seed rooting rate >= 80%, seed germination rate >= 80%, seed purity >= 90%, seed viability >= 80%, 1,000-seed weight >= 250 g, moisture content, <= 10. For the second grade seeds, seed rooting rate >= 50%, seed germination rate >= 60%, seed purity >= 70%, seed viability >= 75%, 1,000-seed weight >= 225 g, moisture content <= 10. For the third grade seeds, seed rooting rate >= 20%, seed germination rate >= 45%, seed purity >= 60%, seed viability >= 45%, 1,000-seed weight >= 205 g, moisture content <= 10. The quality classification criteria of P. suffruticosa seeds have been initially established. PMID- 26137681 TI - [Physiological and biochemical change of Paris seed in after-ripening during variable temperature stratification]. AB - In order to explore the dormancy physiological and biochemical mechanism of Paris seeds, the seed embryo growth courses, and the dynamic change of 5 enzymes, include SOD, POD, CAT, MDH, G-6-PDH were measured during variable temperature stratification. The results indicated that Paris seeds embryo grew quickly after 40 d in warm-stratification (18 +/- 1) degrees C, at the meantime the metabolic activity was significantly strengthened. These facts showed that Paris seeds turned into physiological after-ripening process. After 60-80 d, the morphological embryo after-ripping process basically completed, and the following cold-stratification (4 +/- 1) degrees C furthered Paris seed to finish physiological after-ripening. After 40 d, the activity of MDH decreased while G-6 PDH increased significantly. This showed that the main respiratory pathway of seed changed from TCA to PPP, which benifited breaking seed dormancy. In the whole period of stratification process, the activity variation of SOD and CAT was insignificantly and the activity of POD was enhanced significantly after shifting the seed in cold stratification process. This showed that SOD, CAT had no direct effects on breaking Paris seed dormancy but keeping the seed vigor, while the POD might involve in the process of Paris seed dormancy breaking. PMID- 26137682 TI - [Full-length cDNA cloning of flavonol synthase genes of Carthamus tinctorius and construction plant expression vector]. AB - Flavonol synthase (FLS) is one of the key enzymes in flavonoids metabolic pathways. In this study, middle sequence was obtained from Carthamus tinctorius transcriptome sequencing results. Full-length cDNAs of FLS was cloned from petals of C. tinctorius to FLS by using RT-PCR and RACE technology. Its full-length cDNA was 1,201 bp, with an open reading frame of 1,101 bp and 336 encoded amino acids. The phylogenetic analysis showed that, FLS gene encoded amino acids in C. tinctorius were highly homologous with amino acids in congeneric Compositae species, especially Rudbeckia laciniata. The pBASTA-FLS plant expression vector was successfully built by the molecular biology method, which lays a foundation for further studying biology functions of the gene and biosynthesis mechanism of flavonoids. PMID- 26137683 TI - [Histomorphological study on folk medicine Lysimachia fortunei]. AB - To set standards for histomorphological studies on Lysimachia fortunei, an efficacious and widely applied folk medicine in this study, in order to develop its resources. Its species were identified by observing plant morphology and herbs appearance characters, preparing slices with routine methods and defining structural characters. According to the results of morphologic observation, leaves, stamen and pistil of this plant were different from the descriptions in Flora of China. The whole herb can be used in medicines, mainly including rhizomes, stems and leaves. According to the findings in the first study on microscopic structures, its rhizomes, stems and leaves were characteristic and worth identifying. The transaction tissue structures of rhizomes and stems were under developed and contained endodermis, secretory structures; Stems had sclerenchymata of different shapes of sclereids; Leaves were bifacial and had vascular bundles under midribs, which were surrounded by parenchymal sheathes. On the surface of leaves, stomata, glandular hairs and keratin lines were morphologically different in upper and lower epidermis. The herbal power had glandular hairs, sclereids and vessels. In conclusion, herbs of L. fortunei can be identified by the above histomorphological characteristics, which lays a foundation for further development and application of L. fortunei. PMID- 26137684 TI - [Effect of terpene penetration enhancer and its mechanisms on membrane fluidity and potential of HaCaT keratinocytes]. AB - The aim of this paper was to investigate the effect of terpene penetration enhancers on membrane fluidity and membrane potential using HaCaT keratinocytes, and study the potential mechanisms of these terpene compounds using as natural transdermal penetration enhancer. Six terpene compounds, namely menthol, limonene, 1,8-cineole, menthone, terpinen-4-ol and pulegone, were chosen in this study on account of their good penetration-enhancement activities. The cytotoxicity of these terpene compounds was measured using an MTT assay. The fluorescence recovery after photobleaching (FRAP) technique was employed to measure the change of membrane fluidity of HaCaT cells. The flow cytometer was used to study the alteration of membrane fluidity of HaCaT cells, and investigate the effect of terpene compounds on intracellular Ca2+. It was found that 6 terpene compounds possessed low cytotoxicity in comparison to the well established and standard penetration enhancer azone. Those terpene compounds could significantly enhance HaCaT cells membrane fluidity and decrease HaCaT cells membrane potentials. Meanwhile, after treated with various terpene compounds, the Ca2(+)-ATPase activity and intracellular Ca2+ of HaCaT cells was decreased significantly. Terpene penetration enhancers perhaps changed the membrane fluidity and potentials of HaCaT cells by altering the Ca2+ balance of the cell inside and outside, resulting in the low skin permeability to increase the drug transdermal absorption. PMID- 26137685 TI - [Investigation of elemental concentration and extraction rate of polysaccharides from Liuwei Dihuang prescription" by ICP-MS]. AB - A method was established for the simultaneous analysis of 25 trace elements and heavy metals in polysccharides from Liuwei Dihuang prescription, including Li, Be, B, Ti, Mg, Al, V, Cr, Mn, Co, Fe, Ni, Cu, Zn, Ga, As, Sr, Cd, Sn, Sb, Ba, Hg, Tl, Pb, Bi. The different rate of elemental extraction in Al, Fe, Mg, B, Ti, Mn, Zn, Sr, Ba was made in water and different concentration of alcohol. The samples, digested via microwave, calibrated by internal standard elements such as Ge and In, with bush branches and leaves as the controlled reference standard, were inlet into ICP-MS to analyze the contents of the 24 trace elements and heavy metals. The detection limits of the 24 elements were in the range of 0.007-2.225 ug . L(-1), while the RSD was below <= 4. 0%, with their recovery ranging from 84. 1% to 116%. Big different of the elemental extraction rates could be found by using different ethanol solutions. The method is simple, rapid and accurate, and can be used for the quality control of trace elements and heavy metals in Liuwei Dihuang polysccharides. With the aid of the obtained result, we may increase the extraction of necessary element while making an attempt at multi-element speciation in polysccharides from Liuwei Dihuang. PMID- 26137686 TI - [Comparison of processed and crude Polygoni Multiflori Radix induced rat liver injury and screening for sensitive indicators]. AB - To investigate the difference of liver injury in rats gavaged with crude and processed Polygoni Multiflori Radix. The 75% ethanol extract of crude and processed Polygoni Multiflori Radix (50 g . kg(-1) crude medicine weight/body weight) were continuous oral administered to rats for 6 weeks. Serum biochemical indicators were dynamically detected, the change of liver histopathology was assessed 6 weeks later. Principal component analysis (PCA) was adopted to screen sensitive indicator of the liver damage induced by polygoni multiflori radix. Biochemical tests showed that the crude Polygoni Multiflori Radix group had significant increase of serum ALT, AST, ALP, DBIL and TBIL (P < 0.01 or P < 0.05) and significant decreases of serum IBIL and TBA (P < 0.01 or P < 0.05), while the processed Polygoni Multiflori Radix group showed no obvious changes, compared to the untreated normal group. Histopathologic analysis revealed that crude Polygoni Multiflori Radix group exhibited significant inflammatory cells infiltration in portal area around the blood vessels, tissue destruction and local necrosis of liver cells. There were not obvious pathological changes in processed Polygoni Multiflori Radix group. The results demonstrated that the injury effect of processed Polygoni Multiflori Radix on liver injury of rats was significantly lower than that of unprocessed, and that processing can effectively reduce the hepatotoxicity of Polygoni Multiflori Radix. Traditional transaminase liver function indicators were not sensitive for crude Polygoni Multiflori Radix induced liver damage. The serum content of DBIL and TBIL can reflect the liver damage induced by crude Polygoni Multiflori Radix early and can be sensitive indicators for clinical monitoring the usage of it. PMID- 26137687 TI - [Investigating mechanism of toxicity reduction by combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata on terms of proteins self assembly]. AB - The combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata can increase efficacy and decrease toxicity. This study started from the phenomena of protein self-assembly in the mixed decoction of Glycyrrhizae Radix et Rhizoma with Aconiti Lateralis Radix Preparata. The attenuated mechanism was explored between the combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata by using the protein of Glycyrrhizae Radix et Rhizoma and aconitine which was the major toxic component of Aconiti Lateralis Radix Preparata. Glycyrrhizae Radix et Rhizoma protein with aconitine could form stable particles which particle mean diameter was (206.2 +/- 2.02) nm and (238.20 +/- 1.23) nm at pH 5.0 in normal temperature. Through the mouse acute toxicity experiment found that injection of aconitine monomer all mice were killed, and injection of Glycyrrhizae Radix et Rhizoma protein-aconitine particles with the same content of aconitine all mice survived. Survey the stability of Glycyrrhizae Radix et Rhizoma protein-aconitine shows that the colloid particles is stable at room temperature, and it has the possibility to candidate drug carrier. Glycyrrhizae Radix et Rhizoma protein can reduce the toxicity of aconitine through self-assembly. PMID- 26137688 TI - [A novel chromene with anti-tumor activities from fungus Phomopsis sp]. AB - A new chromene (1) and six known compounds identified as 6-hydroxymellein (2), 6 hydroxy-5-methylmellein (3) nectriapyrone (4), chermesinone A(5), chermesinone B(6), and pomopxanthone A(7), were isolated in our investigation of the cytotoxic constituents from the fermented rice substrate of endophytic fungus Phomopsis sp. HCCB03519. The structures of these com pounds were elucidated through spectroscopic data analysis. All compounds exhibited inhibitory activities against cancer cell lines. Compound 7 showed stronger inhibition against cancer cells than the positive control 5-Fu. PMID- 26137689 TI - [Study on chemical constituents of Inula cappa]. AB - Column chromatographies over silica gel, Sephadex LH-20, reverse phase C18, and MCI, and semi-preparative HPLC were used for separation and purification of constituents from Inula cappa. The 22 compounds were obtained and their strutures were determined by NMR and MS spectra data as nine flavonoids: luteolin (1), apigenin (2), chrysoeriol (3), artemetin (4), 2', 5-di- hydroxy-3, 6, 7, 4', 5' pentamethoxyflavone (5), chrysosplenol C (6), apigenin-5-0-beta-D-glucopyranoside (7), luteolin-3-methyl, luteolin-3-methylether-4'-0-beta-D-glucopyranoside (8), luteolin-4'-0-beta-D-glucopyranoside (9); four triterpenes: darma-20, 24-dien- 3beta-0-acetate (10), darma-20, 24-dien-3beta-ol (11), epirfiedelanol (12), friedelin (13); three coumarins: scopoletin (14) , isosco- poletin (15) , scopolin(16) , and other types of compounds stigmasta-5, 22-dien-3beta-0-7-one (17), stigmasterol (18), palmitic acid (19), linoleic acid (20), linoleic acid methyl ester (21), (E) -9, 12, 13-trihydroxyoetadee-10-enoie acid (22). Compound 5 is a new natural product. Compounds 3-9, 15, 17, 21, and 22 were isolated from this genus for the first time. PMID- 26137690 TI - [Chemical constituents of Osmanthus fragrans]. AB - By Silica gel, Sephadex LH-20 and other materials for isolation and purification and by physicochemical methods and spectral analysis for structural identification, 32 compounds were isolated and identified from ethyl acetate portion of alcohol extract of the Osmanthus fragrans. Their structures were identified as boschniakinic acid (1), ursolaldehyde (2), augustic acid (3), arjunolic acid (4), 5-hydroxymethyl-2-furancarboxaldehyde (5), isoscutellarein (6), 6, 7-dihydroxycoumarin (7), 2alpha-hydroxy-oleanolic acid (8), quercetin-3-0 beta-D-glu-copyranoside (9), D-allito (10), 5, 4'-dihydroxy-7- methoxyflavone-3-0 beta-D-glucopyranoside (11), 5,7-dihydroxychromone (12), lupeol (13), naringenin (14), acetyloleanolic acid (15), chlorogenic acid (16), kaempferol-3-0-beta- D glucopyranoside (17), oleanolic acid (18), kaempferol-3-0-beta-D-galactopyanoside (19), 3', 7-dihydroxy-4'-methoxyisoflavon (20), ergosta-4,6,8 (14), 22-tetraen-3 one (21), p-hydroxycinnamic acid (22), syringaresinol (23), 3,4 dihydroxyacetophenonel (24), beta-sitosterol (25), ethyl p-hydroxyphenylacetate (26), benzoic acid (27), caffeic acid (28), coelonin (29), p-hydorxy-phenylacetic acid (30), p-hydroxyacetophenone (31), and methyl-p-hydroxphenylacetate (32). Except for compounds 2, 4, 5, 8-11, 13, 15, 18, 20, 25, and 27, the rest were isolated from the Osmanthus fragrans for the first time. PMID- 26137691 TI - [Studies on chemical constituents of Zhuang medicine Excoecaria venenata and their cytotoxic activity]. AB - Fourteen compounds were isolated from 95% ethanol extract by silica gel, MCI, and ODS column chromatography. These compounds were respectively identified as quercetin (1), kaempferol (2), (+)-catechin (3), fraxin (4), protocatechuic acid (5), gallic acid (6), methyl gallate (7), ethyl gallate (8), apocynol A (9), baccatin (10), cerevisterol (11), ellagic acid (12), 3, 3',4'-tri-0-methylellagic acid(13) and N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate(14) by analyzing their spectral data and comparing with the previously reported literatures. Except for gallic acid (6), all other compounds were isolated from this plant for the first time. Compounds 1, 2 and 6 showed moderate anti proliferation activities on tumor cells. PMID- 26137692 TI - [Qualitative and quantitative analysis of dodecatetraenamides A, B in Asari Radix et Rhizoma]. AB - To develop an analytic method for qualitative and quantitative analysis of dodecatetraenamides A, B in 42 samples of two official species of Asari Radix et Rhizoma( ARR) (37 samples of Asarum heterotropoides var. mandshuricum with different collection time and 5 samples of Asarum sieboldiivar. seoulense). The HPLC-IT-TOF-MS/MS methods for the qualitative and UPLC-PDA methods for the quantitative analysis were established. Dodecatetraenamides A, B were identified by comparing the retention time, UV absorption spectrum and quasi-molecular ion peak [ M + H]+ with the reference compound using HPLC-IT-TOF-MS/MS. The content of dodecatetraenamides A and B in ARR were determined by UPLC-PDA. The separation was successfully carried out on a ACQUITY UPLC BEH C18 (2.1 mm x 100 mm, 1.7 um) column eluted with mobile phases of water (A) and acetonitrile (B) in gradient program (0-3 min, 35% B; 3-5 min, 35%-36% B; 5-6 min, 36%-43% B; 6 min-11 min 43% B; 11-12 min, 43%-100% B). The column temperature was 45 degrees C, and the detection wavelength was set at 254 nm. The flow rate was 0.6 mL . min(-1). On one level mass spectrometry scanning, the results showed that the quasi-molecular ion [M + H] + of both dodecatetraenamides A and B were m/z 248.20. The quantitative method with UPLC-PDA has made the baseline separation of the constituents, which were reported as mixtures in the most literatures. The average recovery of dodecatetraenamides A and B were 97.90% and 99.86%, the relative standard deviation were 0.4% and 1.1%, respectively. The contents of dodecatetraenamides A, B in all ARR samples was in the range of 0.11-3.89 and 0.24-6.65 mg . g(-1). Their contents reduced with the extension of storage time. Compared with the samples of 2013, the average content of the two constituents in the samples collected in year 2002-2003 reduced 34% and 36%, respectively (P < 0.05). Compared the A. sieboldii var. seoulense and A. heterotropoides var. mandshuricum with the same collective time and production area, the average contents of the two constituents in latter were up to (1.59 +/- 0.75) mg . g(-1) and (2.90 +/- 1.17) mg . g(-1), respectively, significantly higher than that in A. sieboldii var. seoulense (dodecatetraenamide A were (0.78 +/- 0.52) mg . g( 1), dodecatetraenamide B were (1.69 +/- 0.83) mg . g(-1)) (P < 0.05). The content of the dodecatetraenamide A in overground part was in the range of 0.11-0.33 mg . g(-1), dodecatetraenamide B was 0. 24-0.60 mg . g(-1), which were much lower than that of the underground part of ARR (dodecatetraenamide A was in the range of 0.73-3.89 mg . g(-1), dodecatetraenamide B was 2.11-6.24 mg . g(-1)). The method was certified to be simple, accurate and reliable and could be used for qualitative and quantitative analysis of dodecatetraenamide A and B in different species of ARR, also can be used for the comprehensive quality control of traditional Chinese medicine, Asari Radix et Rhizoma. PMID- 26137693 TI - [Simultaneous determination of four flavonoids in Wikstroemia indica by HPLC]. AB - The HPLC method was established to simultaneously determine the contents of myricetin, luteolin, apigenin and kaempferol in Wikstroemia indica ( L. ) C. A. Mey. The method was carried out on a Diamonsil C18 column (4. 6 mm x 250 mm, 5 um) eluted with the mobile phases of water containing 0.15% phosphoric acid and acetonitrile in gradient mode. The UV detection wavelength was 365 nm. The flow rate was 1.0 mL . min(-1) and the column temperature was set at 30 degrees C. All the standard compounds showed a good linearity in the range of 0.100 8-1.008 (r = 0.999 2), 0.484 8-4.848 (r = 0.999 0) , 1. 354-13. 54 (r = 0.999 6), 0.316 8 3.168 mg . L(-1) (r = 0.999 0) for myricetin, luteolin, apigenin and kaempferol, respectively. The average recoveries of these four flavonoids were 98.5%, 100.9%, 99.7% and 98.9% with RSD 1.2%, 1.7%, 0.81% and 1.6%, respectively. In conclusion, the method is simple, rapid and accurate. It can be applied for the quality control of Wikstroemia indica. PMID- 26137694 TI - [Contamination level of aflatoxin B1 in lotus seeds rapid screening by indirect competitive ELISA method]. AB - A simple and cost-effective indirect competitive enzyme-linked immune sorbent assay (ic-ELISA) was developed to rapidly screen the content of aflatoxin B1 (AFB1) in lotus seeds, and the results were confirmed by ultra-fast liquid chromatography-tandem mass spectrometry( UFLC-MS/MS). Matrix-matched calibration expressed a good linearity ranging from 0. 171 to 7. 25 ug . L(-1) for AFB, with R2 > 0.978. The medium inhibitory concentration( IC50 ) for AFB1 was 1.29 ug . L( 1), the recovery for AFB1 was 74.73% to 126.9% with RSD < 5%, and the limit of detection (IC10) was 0.128 ug . L(-1). The developed ic-ELSIA method was applied to rapid analysis of AFB, in 20 lotus seeds samples and the results indicated that the contents of AFB, in samples 1-15 were in the range of 1. 19- 115. 3 ug . kg(-1) and in 40% of the samples exceeded the legal limit(5 ug . kg(-1)), while the contamination rate of AFB, in samples 16-20 was 40%. Pearson correlation coefficient(r) reached 0.997 for AFB1 content in the samples detected by ic-ELSIA and UFLC-MS/MS methods. The results proved that the developed ic-ELISA method is simple, sensitive and reliable, and can be used for rapid and high-throughput screening of AFB1 in lotus seeds PMID- 26137695 TI - [Inhibitory effects of butyl alcohol extract of Baitouweng decoction on yeast-to hyphae transition of Candida albicans isolates from VVC in alkaline pH environment]. AB - OBJECTIVE: To investigate the effects of butyl alcohol extract of Baitouweng decoction ( BAEB) on yeast-to-hyphae transition of Candida albicans isolates from vulvovaginal candidiasis (VVC) in alkaline pH. METHOD: Serial 2-fold dilution assay was used to determine the minimal inhibitory concentrations (MICs) of Baitouweng decoction extracts against C. albicans isolates from VVC, XTT assay was applied to determine the metabolic activity of C. albicans hypha treated by BAEB for 6 h. The morphological change of C. albicans treated by BAEB was inspected at different pH by inverted microscope, fluorescence microscope, scanning electron microscopy (SEM). Solid agar plate and semi-solid agar were utilized to evaluate colony morphology and invasive growth of C. albicans, respectively. Quantitative Real-time PCR (qRT-PCR) was adopted to observe the expressions of hyphae-specific genes including HWP1, ALS3, CSH1, SUN41 and CaPDE2. RESULT: The MIC of BAEB against C. albicans is less than that of other extracts; hyphae grow best at pH 8. 0; 512 mg . L(-1) and 1,024 mg . L(-1) BAEB could inhibit formation of hyphae and influence colony morphology. When treated by 512 mg . L(-1) and 1,024 mg . L(-1) BAEB, the colonies became smooth; while by 0 and 256 mg . L(-1) BAEB, the colonies became wrinkled. In semi-solid agar, the length of hyphae decreased steadily as the concentration of BAEB lowered. The expression of HWP1, ALS3, CSHl, SUN41 were downregulated by 5.12, 4.26, 3.2 and 2.74 folds, and CaPDE2 was upregulated by 2.38 fold. CONCLUSION: BAEB could inhibit yeast-to-hyphae transition of C. albicans isolates from VVC in alkaline pH. PMID- 26137696 TI - [Effect of MDG-1, a polysaccharide from Ophiopogon japonicas, on diversity of lactobacillus in diet-induced obese mice]. AB - For understanding the effect of MDG-1, a water-soluble beta-D-fructan polysaccharide from Ophiopogon japonicas, on intestinal microecological balance, especially on the changes of lactobacillus, sixty 8-week-old male C57BL/6J mice were given a high-fat diet for six weeks and were also gavaged with saline once a day simultaneously. Then the mice which is below 30 grams or dropped more than 10% through lavage were eliminated and the rest were randomly divided into four groups: diet-induced obese (DIO) model group (n = 12, gavaged with saline), low dose MDG-1 group (n = 12, gavaged with MDG-1, 75 mg . kg(-1)) , medial-dose MDG- 1 group (n = 12, gavaged with 150 mg . kg(-1)), and high-dose MDG-1 group (n = 12, gavaged with 300 mg . kg(-1)) according to the weight and blood glucose; the model group and MDG-1 group were placed on a high-fat diet while the normal control group (n = 12, gavaged with saline) were kept on a low-fat diet through the experiment. After 12-weeks of treatment, feces samples were collected and cultured for intestinal microecological balance analysis. Then the intestinal probiotics were cultured through traditional methods combined with modified gradient gel electrophoresis (DGGE) method. The changes of lactobacillus in each treatment group were also detected by a statistical analysis of the total number of the intestinal flora. We have established the phylogenetic tree by 16S rDNA sequencing and use some molecular identification methods such as PCR-DGGE to analyse the changes of the dominant bacteria floras, and also get the pure culture. In conclusion, different concentrations of MDG-1 can increase the number of the intestinal probiotics, especially Taiwan lactobacillus and Lactobacillus murinus, and improve their diversity and promote proliferation in a dose dependent way. PMID- 26137697 TI - [27-O-(E)-p-coumaric acyl ursolic acid via JNK/SAPK signal pathway regulates apoptosis of human breast cancer MDA-MB-231 cell line]. AB - 27-O-(E)-p-coumaric acyl ursolic acid( DY-17) from Ilex latifolia is a compound of the monomer. To investigate the DY-17 inducing apoptosis in the human breast cancer cell line, the MDA-MB-231 cells were used as research object in this experiment. The proliferation activity of the MDA-MB-231 cells stimulated with the different concentrations of DY-17 (20, 40 umol . L(-1)) was detected at different time( 12, 24, 36, 48, 60,72 h) . We surveyed the DY-17 inducing apoptosis of the MDA-MB-231 cells with the fluorescent staining technology. The rate of MDA-MB-231 cells apoptosis and necrosis was determined by flow cell cytometry (FCC). Moreover, expression of JNK, phosphorylated JNK, Bax, PARP shear and caspase-3 shear related to JNK/SAPK pathways were investigated in every group ( control group, EGF group, EGF + DY-17 40 umol . L(1) group and EGF + SP600125 group) with Western blot. The MTT results showed that, in the presence of DY-17, the proliferation activity of MDA-MB-231 cells decreased in a dose-dependent and time-dependent manner. The apoptosis and necrosis rates of MDA-MB-231 cells with DY-17(20, 40 umol . L(-1)) groups was respectively 31.86%, 49.91% by flow cytometry and significantly increased compared with control group under Fluores- cence microscopy. Up-regulation of the JNK phosphorylation protein expression was observed in EGF group compared with control group. In addition, markedly decreased the expression of JNK phosphorylation protein were also surveyed in EGF + DY-17 40 umol . L(-1) group compared with EGF group. The expression of Bax, shear PARP and shear caspase-3 protein in EGF + DY-17 40 umol . L(-1) group were significantly increased in comparison with EGF group. The results showed DY-17 induced apoptosis of human breast cancer MDA-MB-231 cell line related to down regulating JNK/SAPK signal pathways. PMID- 26137698 TI - [Effect of Huanglian Jiedu decoction in combination with fluconazole on ergosterol of fluconazole-resistant Candida albicans]. AB - OBJECTIVE: To investigate the effects of ethyl acetate extract of Huanglian Jiedu decoction (EAHD) , alone and in combination with fluconazole (FLZ) on FLZ resistant Candida albicans. METHOD: The minimum inhibitory concentrations (MIC) and sessile MIC80 (SMIC80) of EAHD and FLZ to FLZ-resistant C. albicans were determined by CLSI M27-A3 microdilution method, and the synergy of EAHD combined with FLZ were examined by the checkerboard microdilution assay. Agar plate-method was adopted to observe the rate of antifungal activity according to time-kill curve. HPLC and qRT-PCR were utilized to evaluate the changes of ergosterol content and expressions of related genes, respectively. RESULT: MICs of EAHD ranged from 156 to 1,250 mg . L(-1), those of FLZ from 256 to above 2,048 mg . L( 1) with FICI approximate 0.066 in combination; SMIC80 of EAHD were higher than 1,250 mg . L(-1), SMIC80 of FLZ were higher than 512 mg . L(-1) and up to above 2,048 mg . L(-1). Combination group also showed synergy effect except one group showing addition effect. The results of T-K experiment also confirmed obviously fungicidal effect when treated for 12 h. When compared with control groups, the ergosterol was reduced 85% and 50% in the treatments of combination and EAHD alone by HPLC, respective- ly. The expressions of ERG1, ERG2, ERG6, ERG7 and ERG11 were upregulated, and ACS1, ACS2, MET6 were downregulated when exposed to FLZ. The expressions of the above genes were downregulated by treatment of EAHD. The expressions of ERG2, ERG6, ERG11 were upregulated, while ERG1, ERG7, ACS1, ACS2, MET6 were downregulated in combination group. CONCLUSION: The combination of EAHD and FLZ exhibited synergy against FLZ-resistant C. albicans through decreasing the synthesis of ergosterol, and resulting in the breakage of cell membrane. PMID- 26137699 TI - [Study on intersection and regulation mechanism of "efficacy-toxicity network" of aconite in combination environment of Sini decoction]. AB - OBJECTIVE: To explore the intersection and regulation mechanism of "efficacy toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata's action gene in the combination environment of Sini decoction with the network pharmacological method. METHOD: The gene interaction network of Aconiti Lateralis Radix Praeparata, Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma were mined and established with Cytoscape software and Agilent literature search plug-in. The "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata was formed according to its effects in anti-heart failure, neurotoxicity and cardiotoxicity. The target genes were clustered with Clusterviz plug-in. And the possible pathways of the "efficacy-tox- icity network" intersection of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata were forecasted in DAVID database. RESULT: There were five genes related to neurotoxicity, cardiotoxicity and anti-heart failure function of Aconiti Lateralis Radix Praeparata, namely AKT1, BAX, HCC, IL6 and IL8, which formed 47 nodes genes in the "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata. There were 29 and 27 coincident genes in the "efficiency-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata. There were 23 and 17 possible regulatory pathways. CONCLUSION: In the combination environment of Sini decoction, Glycyrrhizae Radix et Rhizoma and Zingiberis Rhizoma may regulate the efficiency-toxicity network of Aconiti Lateralis Radix Praeparata by influencing immune-inflammatory signaling pathway, apoptosis-autophagy signaling pathway, nerve cell and myocardial ischemia and hypoxia protection signaling pathways. PMID- 26137700 TI - [Pharmacokinetic study on dry powder inhalation administration of alpha-asarone in rats]. AB - To study the pharmacokinetic characteristics and absolute bioavailability of alpha-asarone through dry powder inhalation in rats, and compare with that through oral administration and intravenous injection. A HPLC method was established for the determination of alpha-asarone in rat plasma to detect the changes in plasma concentrations of alpha-asarone through dry powder inhalation (20 mg . kg(-1)), oral administration (80 mg . kg(-1)) and intravenous injection (20 mg . kg(-1)) in rats. DAS 2.0 software was used to calculate the pharmacokinetic parameters. The absolute bioavailability of alpha-asarone was calculated according to AUC(0-t)) of administration routes and administration doses. According to the results, alpha-asarone showed good linear relations (r = 0. 999 4) at concentrations between 0.282-14.1 mg . L(-1), with the limit of detection (LOD) at 0.212 mg . L(-1). Through dry powder inhalation, oral administration and intravenous injection of alpha-asarone, the metabolic processes of alpha-asarone in rats conformed to one, two and three compartment models respectively, with the elimination half-life of (95.48 +/- 48.28), (64.34 +/- 27.59), (66.99 +/- 29.76) min. According to the bioavailability formula, the absolute bioavailability of alpha-asarone through dry powder inhalation and oral administration were 78.32% and 33. 60%, respectively. This study showed that significant increase in elimination half-life and absolute bioavailability of alpha-asarone through dry powder inhalation, which lays a theoretical foundation for preparing alpha-asarone dry powder inhalers. PMID- 26137701 TI - [Preliminarily analysis on traditional Chinese medicine advices in Treatise on Febrile Diseases]. AB - To make a systematic analysis on literatures concerning traditional Chinese medicine (TCM) advices in Treatise on Febrile Diseases, and summarize the main connotations of traditional Chinese medicine advices, relevant TCM advices in Treatise on Febrile Diseases were collected, screened, compared, summarized and analyzed according to TCM dosage form preparation methods, TCM administration methods, medication contraindications and nursing after TCM administration. The literatures concerning medications in Treatise on Febrile Diseases were consulted, summarized and compared to standardize medicine advices and facilitate rational clinical application of TCMs. The standard medicine advices were as follows. The boiling water for TCMs shall be tap water and well water. The decoctions that have effects in promoting blood and meridians can be boiled with wine. The decoctions containing toxic components can be boiled with honey. Some TCMs shall be boiled with special methods, e. g. Herba Ephedra that could be boiled before other medicine and skimmed. Japonica rice could be added in decoctions to measure the duration of decoctions. Different dosages were required for different forms (litre, pill, medicine spoon). Administration times, temperature and frequency shall be adjusted according to target positions, functions and stage of illness. As for dietary contraindications during medication, thick porridges are recommended, where foods impacting medicine efficacy are prohibited. Regarding nursing after medication is important to recover physical functions, particularly warm porridges can go with diaphoretic recipes, while thick porridges can go with purgative recipes. And drug efficacies shall be defined by observing urine and excrements, and blood form. In conclusion, Treatise on Febrile Diseases is the first book that discusses TCM advices and records them in details. In this study, new standard medicine advices were proposed to provide important basis for improving clinical advices of TCMs and supports for developing the TCM dispensing technology. PMID- 26137702 TI - [Study on effect of Xiaoaiping in enhancing efficacy of neoadjuvant chemotherapy for breast cancer and its mechanism]. AB - Traditional Chinese medicine (TCM) Xiaoaiping shows a pharmacological activity in treatment of breast cancer. Although neoadjuvant chemotherapy has been more and more widely used in treatment of breast cancer in recent years, no report has been made about the clinical efficacy and mechanism of the combined application of neoadjuvant chemotherapy and Xiaoaiping in treatment of breast cancer. In this study, 66 patients with breast cancer were selected and divided into the control group and the treatment group evenly with the random number table method. All patients received TEC neoadjuvant chemotherapy. On that basis, the treatment group also received the adjuvant therapy of Xiaoaiping injection (60 mL, i. v. , qd). The short-term response rate and the follow-up survival rate of the two groups were observed and compared. Surgical specimens of the patient were collected to observe and compare their expressions of estrogen receptor ER alpha36 in breast cancer tissues with the immunohistochemical method. According to the findings, the overall response rate of the treatment group was 78.79%, which was significantly higher than that of the control group (57.58% , chi2 = 5.48, P < 0.05). Compared with the control group, the treatment group showed significant increases in the disease-free survival (DFS) rate and the total survival rate at the 3rd year and 5th year (all P < 0.05) , and a notable reduction in ER-alpha36 expression in breast cancer tissues (P < 0.05). Based on the our results, Xiaoaiping can significantly enhance short-term ad long-term efficacies of neoadjuvant chemotherapy for breast cancer. Its mechanism may be correlated with the inhibition of ER-alpha 36 expression in breast cancer tissues. PMID- 26137703 TI - [Summary of Hui prescriptions for treating cough]. AB - In this study, by using the method of literature research, 35 prescriptions related to asthma therapy has been screened out from Hui medicine through collecting the ancient and modern literature. A comparison of fragrant medicine between the name in Arab and Chinese herbal medicine is done. The countif function in Microsoft Excel 2007 is used to get the prescriptions of the drug on the frequency statistics, summarizing the common drugs of Hui medicine for asthma are Pinellia, almond, white sugar, walnut. According to the commonly used drugs, the pathogeny and treatment principle about Hui medicine for asthma is preliminarily inferred combining literature research and the related Hui medical theory. In this study, those prescriptions have been classified into 21 cases which are effective and can be used in medical therapy according to the relevant literatures with the development of the Hui people in their long process of formation of the unique diet culture, 14 useful and convenient Halal diet therapies are made up according to the indications, therapies, party name and composition. Halal diet and "medicine and food" herbs are preliminarily analyzed and summarized, which can be convenient for the people to reduce pains through the diet and improve health awareness. PMID- 26137704 TI - [Structural components of Chinese medicine and pharmacology network: systematical overall regulation on pathological network]. AB - Development of the disease is the result of several factors involved in biological network changes. The nature of drug intervention is to regulate these pathological changes to the normal range. Advantages of traditional Chinese medicine (TCM) are to integrally and systematically regulate this biological networks and systematic pathology through multi-targets, multi-levels, multi channels. Structural components TCM provides the controlled and precise basis "substance" for this regulation and also to clarify the "truth" of the nature of the regulation by the network pharmacology. Network pharmacology provides new strategy for the research on mechanism of structural components TCM. This study not only reflects the overall characteristics of the development of the disease, but also fully embodies the essence of TCM for preventing and treating diseases through changing traditional model on "one drug, one gene, one disease". This paper explores systematically the integration essence, features and research strategies of structural components TCM and the network pharmacology, understand the interaction of structural components TCM and body from the perspective of the overall concept of improving or restoring the balance of.biological networks. It is effective measure to reveal the structure of a multi-component for regulating biological networks mechanisms, and also provide new ideas and methods for further scientific research and innovation of structural component TCM. PMID- 26137705 TI - [Brief introduction of research methods of commodity specification and grade of Chinese medicinal materials]. AB - The commodity specification and grade of Chinese medicinal materials is a measure of the quality of traditional Chinese medicines (TCMs), which directly impacts on the safety and effectiveness of clinical medicines. It is an urgent problem to establish a set of standards which can both interpret the scientific connotation of the commodity specification and grade of Chinese medicinal materials and play a significant role on clinical medicines as well as markets. This paper reviews the research methods of the commodity specification and grade of Chinese medicinal materials such as sensory evaluation, chemical assessment, biological evaluation, and cited the applications of various methods for the classification of TCMs. It provides technical support for establishing standards of the commodity specification and grade of Chinese medicinal materials, and also constructs scientific basis for clinical rational drug use. PMID- 26137707 TI - A single incision transaxillary thoracoscopic sympathectomy. AB - BACKGROUND/AIM: Primary hyperhidrosis causes are unknown. The disorder begins in early childhood. It intensifies in puberty and maturity. It is equally present in both sexes. The symptoms exacerbate when the body temperature rises and due to emotional stimuli affecting the sympathetic nerve system. The aim of this study was to demonstrate that video-assisted thoracoscopic surgery (VATS) sympathectomy is a method for primary focal hyperhidrosis permanent treatment. The single incision method in properly selected patients maximizes the intervention effectiveness and minimizes aesthetic side effects. METHODS: This prospective study analysed the findings in patients who had been operated on due to primary focal hyperhidrosis (face, palms, and armpits) using a single small transaxilarry incision in the third inter-rib space at the level of the anterior axillary line with two 5 mm flexible ports. All the patients, with T2-T5 thoracoscopic sympathectomy of the sympathetic chain using a single small incision in the third inter-rib space in the anterior axillary line, were analysed in the period from September 2009 to November 2010 regarding the postoperative morbidity and outcomes of the operation (clinical evaluation and visual analogue scale) with a view to assessing the effectiveness of the surgery conducted in this manner. RESULTS: A total of 47 patients (18 men, 29 women), 18 to 48 years old (29 on average) had underwent 94 bilateral video-assisted thoracoscopic sympathectomies. The sympathectomy was indicated in cases of facial blushing and sweating (6.38%), palmary sweating (34.04%), axillary sweating (14.89%) or both palmary and axillary sweating (44.68%). The largest percentage of patients (98.6%) had left the hospital the following day. The postoperative 30 day's mortality was 0 and the conversion into open surgery was not necessary. As for complications, there had been an occurrence of partial pneumothorax in two patients treated by means of exuflation and chest drain, and one case of unilateral transitory Homer's syndrome. Quarterly and annual postoperative monitoring showed excellent aesthetic effects of the surgery without any residual pain. The complete withdrawal of hyperhidrosis symptoms was noted in 44 (93.62%) of the patients. The recurrence of symptoms following the initial regression was seen in 3 (6.38%) of the patients 12 months after the surgery, whereas the patients surgically treated as a result of facial hyperhidrosis saw a significantly increased sweating of feet. The quality of life improved in 45 (95.6%) of the patients. CONCLUSION: Single incision transaxillary thoracoscopic sympathectomy generates excellent aesthetic and functional results in patients with primary focal hyperhidrosis. PMID- 26137708 TI - Lung tumors: early and delayed ratio of 99mTc-methoxy-2-isobutylisonitrile accumulation. AB - BACKGROUND/AIM: Currently used radiopharmaceuticals are nonspecific and most of them are accumulated by benign tumors as well as inflammatory lesions, abscess or granulomatous lesions. Some factors such as the choice of radiopharmaceutical applied, histopathologic type of tumor, its size, location or previous tumor treatment could influence tumor imaging sensitivity. The aim of this study was to investigate accumulation of 99mTc-methoxy-2-isobutylisonitrile (99mTc-MIBI) by counting early/delayed uptake and release of this radiopharmaceutical inside lung tumors and evaluating possible factors which could be involved in its accumulation. METHODS: Two-phase 99mTc-methoxy-2-isobutylisonitrile single photon emission computed tomography scan (early and delayed scan) was performed in 60 patients with lung tumors (the group 1 - 30 benign, and the group 2 - 30 malignant tumors). We calculated the uptake ratio on early (early ratio - ER), delayed images (delayed ratio - DR) and retention index (RI). Individual influence of etiology, diameter, localization, and histological type on uptake/release values was evaluated with regression analysis. RESULTS: The values of ER and DR were significantly different in both groups (p < 0.01), showing lower values in benign vs malignant lung tumors (ER 1.36 +/- 0.094 and DR 1.25 +/ 0.089 vs ER = 1.93 +/- 0.106 and DR = 1.7 +/- 0.095 respectively). Tumor size showed a significant influence on the change of ER and DR values (p < 0.01), with greater uptake in tumors > 3 cm. RI values showed no significance between the two groups (P > 0.05). CONCLUSION: The uptake ratio of 99mTc-methoxy-2 isobutylisonitrile could be a useful index in differentiating lung tumors, while RI has no influence on this. Among the evaluated factors, ER and DR values are significantly influenced only by the diameter of lung tumor, while localization or different histological types between the groups has no influence on this. PMID- 26137709 TI - Testing of urodynamic dysfunctions in patients with multiple sclerosis. AB - BACKGROUND/AIM: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disorder of the unknown origin leading to multifocal demyelization, axonal damage and the loss of the nervous tissue in various parts of the central nervous system. Most MS patients have decreased functionality of the bladder leading to various dysuria disorders during the course of the illness. However, in 2% of the cases dysuric problems are the first symptoms of the disease. Urodynamic testing could help to diagnose functional disorders of the lower urinary tract, which might not be otherwise possible by performing the standard invasive procedures or noninvasive scans, such us ultrasound, computed tomography or functional magnetic resonance imaging (fMR). METHODS: Urodynamic testing--cystometry with electromyographic (EMG) potentials from the external anal sphincter (EAS), was performed in 34 patients (25 female and 9 male patients). Those patients fulfilled Mc Donald's multiple sclerosis criteria. The urodynamic values were compared to neurological signs and the present disease symptoms. RESULTS: The MS patients with (27) and without (7) miction problems were tested. Detrusor hyperreflexia is the most common finding, present in 58.8% of the cases. More than a half of the patients have detrusor sphincter dissynergia. CONCLUSIONS: Urodynamic testing helps us to determine neurological disorders characteristics and to prepare an appropriate treatment plan. During the course of the disease different urodynamic disfunctions may occur as well as changes in the urinating functionality. The rationale for urodynamic testing in patients suffering from MS before any other treatment procedure is to confirm the diagnosis of dysuric disorders and to secure appropriate treatment. PMID- 26137710 TI - Implant stability and marginal bone level of microgrooved zirconia dental implants: A 3-month experimental study on dogs. AB - BACKGROUND/AIM: The modification of implant surfaces could affect mechanical implant stability as well as dynamics and quality of peri-implant bone healing. The aim of this 3-month experimental study in dogs was to investigate implant stability, marginal bone levels and bone tissue response to zirconia dental implants with two laser-micro-grooved intraosseous surfaces in comparison with nongrooved sandblasted zirconia and sandblasted, high-temperature etched titanium implants. METHODS: Implant surface characterization was performed using optical interferometric profilometty and energy dispersive X-ray spectroscopy. A total of 96 implants (4 mm in diameter and 10 mm in length) were inserted randomly in both sides of the lower jaw of 12 Fox Hound dogs divided into groups of 24 each: the control (titanium), the group A (sandblasted zirconia), the group B (sandolasted zirconia plus microgrooved neck) and the group C (sandblasted zirconia plus all microgrooved). All the implants were immediately loaded. Insertion torque, periotest values, radiographic crestal bone level and removal torque were recorded during the 3-month follow-up. Qualitative scanning electon microscope (SEM) analysis of the bone-implant interfaces of each group was performed. RESULTS: Insertion torque values were higher in the group C and control implants (p < 0.05). Periotest values increased in all the periods in proportion to the extent of microgrooving as follows: the group C > the control > the group B > the group A (p < 0.05). Radiographic measurements showed minimal crestal bone loss at 3 months for microgrooved zirconia implants (groups C and B) and control implants compared with the group A implants (p < 0.05). The removal torque values increased with time for all the groups as follows: the group C > the control > the group B > the group A (p < 0.05). SEM showed that implant surfaces of the groups B and C had an extra bone growth inside the microgrooves that corresponded to the shape and direction of the microgrooves. CONCLUSION: The addition of microgrooves to the entire intraosseous surface of zirconia dental implants enhances primary and secondary implant stability, promotes bone tissue ingrowth and preserves crestal bone levels. PMID- 26137711 TI - The efficacy of hydrothermally obtained carbonated hydroxyapatite in healing alveolar bone defects in rats with or without corticosteroid treatment. AB - BACKGROUND/AIM: Autogenous bone grafting has been the gold standard in clinical cases when bone grafts are required for bone defects in dentistry. The study was undertaken to evaluate multilevel designed carbonated hydroxyapatite (CHA) obtained by hydrothermal method, as a bone substitute in healing bone defects with or without corticosteroid treatment in rats as assessed by histopathologic methods. METHODS: Bone defects were created in the alveolar bone by teeth extraction in 12 rats. The animals were initially divided into two groups. The experimental group was pretreated with corticosteroids: methylprednisolone and dexamethasone, intramuscularly, while the control group was without therapy. Posterior teeth extraction had been performed after the corticosteroid therapy. The extraction defects were fulfilled with hydroxyapatite with bimodal particle sizes in the range of 50-250 MUm and the sample from postextocactional defect of the alveolar bone was analyzed pathohystologically. RESULTS: The histopatological investigations confirmed the biologic properties of the applied material. The evident growth of new bone in the alveolar ridge was clearly noticed in both groups of rats. Carbonated HA obtained by hydrothermal method promoted bone formation in the preformed defects, confirming its efficacy for usage in bone defects. Complete resorption of the material's particles took place after 25 weeks. CONCLUSION: Hydroxyapatite completely meets the clinical requirements for a bone substitute material. Due to its microstructure, complete resorption took place during the observation period of the study. Corticosteroid treatment did not significantly affect new bone formation in the region of postextractional defects. PMID- 26137712 TI - The prevalence of substance use among adolescents and its correlation with social and demographic factors. AB - BACKROUND/AIM: Adolescence is the period of greatest risk of starting to use substances: cigarette smoking, alcohol and illicit drugs. In the first decade of this millennium substance use among adolescents has increased. The aim of this study was to explore the prevalence of substances use among adolescents and its correlation with social and demographic factors. METHODS: The study was conducted among adolescents in Novi Sad during 2010-2011 and included 594 conveniently selected adolescents (275 male and 319 female), aged 15-19 years. A special questionnaire was used and statistical analysis performed in SPSS17. The correlation between parameters was evaluated by the Pearson correlation method and frequency differences were analysed using chi2 test and starting level was p < 0.05. RESULTS: The prevalence of substance use was statistically higher in males. Cigarettes were smoked daily by 21.45% males and 15.67% females (p < 0.01), alcohol was consumed by 81.6% males and 69.11% females (p < 0.001) and illicit drugs were used by 13.65% males and 8.30% females (p < 0.05). There was a positive correlation between smoking cigarettes and alcohol consumption, but negative between smoking cigarettes and the use of illicit drugs (p < 0.01). The prevalence of substance use was statistically higher among adolescents with poor achievement in school (p < 0.01), who lived in a broken home (illicit drugs p < 0.01) and who had more pocket money (cigarette smoking p < 0.01, and alcohol consumption p < 0.5). CONCLUSION: Stable family, lower amount of pocket money weekly and good school performance are protective factors in prevention of substances use among adolescents. PMID- 26137713 TI - Correlation between the Finnish Diabetes risk Score and the severity of coronary artery disease. AB - BACKGROUND/AIM: The FINish Diabetes RIsk SCore (FINDRISC) which includes age, body mass index (BMI), waist circumference, physical (in) activity, diet, arterial hypertension, history of high glucose levels, and family history of diabetes, is of a great significance in identifying patients with impaired glucose tolerance and a 10-year risk assessment of developing type 2 diabetes in adults. Due to the fact that the FINDRISC score includes parameters which are risk factors for coronary artery disease (CAD), our aim was to determine a correlation between this score, and some of its parameters respectively, with the severity of angiographically verified CAD in patients with stable angina in two ways: according to the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score and the number of diseased coronary arteries. METHODS: The study included 70 patients with stable angina consecutively admitted to the Clinic of Cardiology, Military Medical Academy, Belgrade. The FINDRISC score was calculated in all the patients immediately prior to angiography. Venous blood samples were collected and inflammatory markers [erythrocyte sedimentation rate (ESR), leucocytes, C-reactive protein (CRP), total cholesterol, HDL cholesterol, triglycerides and fasting glucose] determined. Coronary angiography was performed in order to determine the severity of coronary artery disease according to the SYNTAX score and the number of affected coronary vessels: 1-vessel, 2-vessel or 3-vessel disease (hemodynamically significant stenoses: more than 70% of the blood vessel lumen). The patients were divided into three groups regarding the FINDRISC score: group I: 5-11 points; group II: 12-16 points; group III: 17-22 points. RESULTS: Out of 70 patients (52 men and 18 women) enrolled in this study, 14 had normal coronary angiogram. There was a statistically significant positive correlation between the FINDRISC score and its parameters respectively (age, body mass index-BMI, waist circumference) and the severity of CAD according to the SYNTAX score (p < 0.001) and the number of diseased coronary arteries (p < 0.001). The patients with higher FINDRISC score (groups II and III) had more severe and extensive-CAD according to the SYNTAX score than the group I. The odds ratio with 95% confidence intervals (CI) between the group III and the group I was 5.143 (95% CI 1.299-20.360, p = 0.002) and between the group II and the group I 5.867 (95% CI 1.590- 21.525, p = 0.007). There were no differences in odds ratio for multivessel disease according to FINDRISC score between the group II and the group III [1.141; (95% CI 0.348-3.734). In the group I mean SYNTAX score was 5.18, and more than 70% of patients had normal coronary angiogram. In the group II mean SYNTAX score was 17.06, and more than 70% of patients had 2-vessel disease and 3-vessel disease, and in the group III mean SYNTAX score was 18.89, and 2-vessel and 3-vessel disease had 36.36% and 31.82% patients, respectively. In multiple regression analysis, where SYNTAX score was dependent variable, and age, BMI, waist circumference, FINDRISC score were independent variables, we found that only FINDRISC score was independent predictor of SYNTAX score. CONCLUSION: The obtained results suggest a statistically significant correlation between the FINDRISC score and its parameters (age, BMI, waist circumference) and the severity of CAD according to the SYNTAX score and the number of diseased coronary arteries. The FINDRISC score may be useful in identifying patients at the high risk for coronary artery disease. PMID- 26137714 TI - Determinants of smoking and smoking cessation among health professionals in Serbia: A cross-sectional study. AB - BACKGROUND/AIM: Bearing in mind a high smoking prevalence in Serbia (34% in adult population; men 38%, women 30%) and leading role of health professionals in intervention and prevention, a cross-sectional study was performed smong the representative sample of health professionals in Serbia. The aim of the study was to identify predictors of smoking and smoking cessation prior to the total smoking ban in November 2010. METHODS: In this nationwide study, 3,084 physicians and nurses from 4 types of institutions and four geographical regions were selected and 2,282 included (response rate 74.0%). Data were collected using a self-administered structured questionnaire. Standard statistical methods were used to calculate prevalence rates, and multivariate logistic regressions to evaluate independent predictors of smoking pattern. Risks were expressed as odds ratios (OR) which represent approximation of relative risks of exposed persons with 95% confidence intervals (95% CI). RESULTS: We found a high smoking prevalence of 38.0%, the same for women and men (37.8% and 37.6%, respectively; p = 0.138), higher among nurses (41.7%) than physicians (29.1%) (p = 0.000), as well as among those employed in general hospitals (42.6%) and institutes of public health (43.8%) (p = 0.000). Significantly increased risk of being an ever or current smoker was noticed for nurses (OR = 1.75, 95% CI 1.42-2.14; and OR = 1.91, 95% CI 1.52-2.40, respectively), those employed in general hospitals (OR = 1.37, 95% CI 1.09-1.73 and OR = 1.40, 95% CI 1.09-1.79, respectively), and with worse self-estimated health (OR = 1.15, 95% CI 1.02-1.30; and OR = 1.17, 95% CI 1.02-1.34, respectively). Intentions to quit smoking or to reduce the number of cigarettes were more frequent in women (OR = 1.51, 95% CI 1.01-2.27) and participants who worse evaluated their health (OR = 1.74, 95% CI 1.39-2.18). CONCLUSION: High smoking prevalence in health professionals could be a barrier for the full implementation of smoking ban in health institutions in Serbia. Smoking cessation programs at workplaces, formal education in smoking cessation techniques, and better Law enforcement by health administrations should be implemented. PMID- 26137715 TI - Experimental pleural empyema model in rabbits: Why, how and what are the next steps. AB - BACKGROUND/AIM: The use of new therapeutic methods to prevent development of fibrothorax as the final complication of the human pleural infections requires research with experimental animals. The aim of this study was to standardize the procedures for the establishment of our own experimental model of empyema in rabbits, since it should be able to offer similar conditions found in human pleural infections. METHODS: This experiment included 15 chinchilla rabbits, weighing from 2.3 to 2.8 kg. There were 12 rabbits in the experimental group, while 3 rabbits formed the control group. On the first day, we administered 0.4 0.5 mL of turpentine in the right pleural space of the rabbits from the experimental group in order to provoke sterile exudative pleurisy. After 24 h we injected 1 mL of Staphylococcus aureus and 1 mL of Escherichia coli bacteria in the same concentration of 4.5 x 10(8) bacteria/mL. Thoracocentesis for the pleural fluid analysis was performed 24, 48, 72, and 96 h after bacteria instillation. In these pleural samples we estimated the number of leucocytes and the values of lactate dehydrogenase (LDH), glucose and pH in pleural fluid, as well as the presence of bacteria. We did not protect the animals with antibiotics, and on the day 7 of the experiment they were sacrificed with the lethal dose of barbiturate (iv). The lung from the empyemic side of all experimental animals and the lung of one control animal were histopathologically examined. RESULTS: A total of 4 animals had a small amount of clear pleural fluids or there was no fluid obtained with thoracocentesis 24 and 48 h after the bacteria instillation. after the bacteria instillation. In the remaining 8 rabbits 24 h after bacteria administration the mean values (+/- SD) of the parameters monitored were as follows: Le 34.75 +/- 6.13 x 109/L, LDH 17,000 +/- 4,69 U/L, glucose 1.23 +/- 0.45 mmol/L, and pH 6.975 +/- 0.15. The obtained values met the criteria for the evaluation of effusion as pleural empyema or complex and complicated pleural effusion (LDH > 1000 U/L, glucose < 2.31 mmol/L and pH < 7.20). Bacterial cultures were positive in 5 out of 8 first pleural samples and in only 2 samples after 48 h of bacteria administration. There was a positive correlation between the number of leukocytes and the LDH value (r = 0.071, p < 0.001), and a negative correlation between the number of leukocytes and the glucose level (r = 0.864, p < 0.001), and the leukocytes number and pH of the pleural fluid (r = 0.894, p < 0.001). The mean glucose value increased after 48 h (3.23 +/- 0.44 mmol/L), and the pH value rose after 72 h (7.22 +/- 0.03) which was beyond the empyema level. CONCLUSION: The creation of the experimental empyema model is a very delicate work with uncertain success. Its value and importance are crucial for pleural pathology research. With the intention to obtain a more empyemic pleural reaction we created a model with two different human pathogen bacteria. We generated the satisfactory results, but not as good as those contained in some of the reference literature data. PMID- 26137716 TI - A preliminary study on local administration of dexamethasone after tooth extraction--Better preservation of residual alveolar ridge? AB - BACKGROUND/AIM: It is important that the height of the edentulous alveolar ridge after tooth extraction remains at a reasonable acceptable level for as long as possible. The aim of this study was to report preliminary results of the clinical effect of local oral submucous administration of dexamethasone after tooth extractions in order to prepare alveolar supporting tissues for acceptance of removable dentures. METHODS: In a total of 15 patients (11 partially and 4 completely edentulous) the quantity of 0.25 mL to 0.5 mL of dexamethasone was injected bucally and orally in the region of the tooth socket after complicated extractions. RESULTS: Healing of extraction wounds was uneventful in all the patients, without pain or local inflammation. CONCLUSION: Dexamethasone can be locally applied to oral tissues to prevent post-extraction inflammation and extensive resorption of the residual alveolar ridge. The obtained results are promising for patients undergoing classic prosthodontic rehabilitation soon after tooth extraction, demonstrating that there are no adverse effects after local oral corticosteroids administration. PMID- 26137717 TI - Congenital cholesteatoma of the middle ear--uncommon clinical presentation. AB - INTRODUCTION: Congenital cholesteatoma of the middle ear is un uncommon and yet not well-defined disease. Only few cases of cholesteatoma in thefossa ovalis with unusual clinical presentation have been reported in medical literature. CASE REPORT: We reported a 16-year-old girl with congenital cholesteatoma in the fossa ovalis with minimal clinical presentation. A small mass was found occluding the fossa ovalis and mimicking otosclerotic process within tympanic cavity. The operation started as stapedotomy, and when the process was confirmed it converted to mastoidectomy via the retroauricular approach. CONCLUSION: The diagnosis of congenital cholesteatoma in children should always be considered, even if the clinical symptoms imitate other ear disorders, in our case otosclerosis. PMID- 26137718 TI - Sarcoidosis of the pleura--A case report. AB - INTRODUCTION: Pleural involvement is an uncommon manifestation of sarcoidosis. It may manifest as pleural effusion, pneumothorax, pleural thickening and nodules, hydropneumothorax, trapped lung, hemothorax, or chylothorax. The incidence of pleural effusion with sarcoidosis ranges from 0% to 5% but has been reported to be as high as 7.5%. Pleural effusions complicate sarcoidosis in < 3% of patients. CASE REPORT: We reported a 64-year-old male patient with chronic multiorgan sarcoidosis. This patient developed pleural sarcoidosis with massive pleural effusion several years after the diagnosis of sarcoidosis. A definitive diagnosis of a sarcoid pleural effusion was based on a biopsy demonstrating noncaseating granuloma. The patient responded well to the treatment (methotrexate and methylprednisolone) with a complete withdrawal of pleural effusion following five weeks of the treatment beginning. CONCLUSION: The presented patient is a rare case of pleural involvement of sarcoidosis with massive effusion, who responded well to the treatment. PMID- 26137719 TI - Orbital lymphoma associated with Graves' disease: A case report. AB - INTRODUCTION: The presence of bilateral exophthalmos and palpebral, periorbital edema associated with hyperthyroidism is most often considered as an initial sign of Graves' ophthalmopathy. However, in up to 20% of cases, Graves' ophthalmopathy might precede the occurence of hyperthyroidism, which is very important to be considered in the differential diagnosis, especially if it is stated as unilateral. Among other less common causes of non-thyroid-related orbitopathy, orbital lymphoma represents rare conditions. We presented of a patient with Graves' disease, initially manifested as bilateral orbitopathy and progressive unilateral exophthalmos caused by the marginal zone B-cell non-Hodgkin lymphoma of the orbit. CASE REPORT: A 64-year-old man with the 3-year history of bilateral Graves' orbitopathy and hyperthyroidism underwent the left orbital decompression surgery due to the predominantly left, unilateral worsening of exophthalmos resistant to the previously applied glucocorticoid therapy. A year after the surgical treatment, a substantial exophthalmos of the left eye was again observed, signifying that other non-thyroid pathology could be involved. Orbital ultrasound was suggestive of primary orbital lymphoma, what was confirmed by orbital CT scan and the biopsy of the tumor tissue. Detailed examinations indicated that the marginal zone B-cell non-Hodgkin lymphoma extended to IV - B-b CS, IPI 3 (bone marrow infiltration: m+ orbit+). Upon the completion of the polychemiotherapy and the radiation treatment, a complete remission of the disease was achieved. CONCLUSION: Even when elements clearly indicate the presence of thyroid-related ophthalmopathy, disease deteriorating should raise a suspicion and always lead to imaging procedures to exclude malignancy. PMID- 26137721 TI - [Dr. Risto Ivanovski]. PMID- 26137722 TI - The Greater Good. PMID- 26137720 TI - Improvement of post-hypoxic action myoclonus with levetiracetam add-on therapy: A case report. AB - INTRODUCTION: Chronic post-anoxic myoclonus, also known as Lance-Adams syndrome, may develop following hypoxic brain injury, and is resistant to pharmacological therapy. CASE REPORT: The patient we presented developed post-anoxic action myoclonus with severe, completely incapacitating myoclonic jerks. Myoclonus did not respond to the treatment with commonly used agents, i.e. valproate and clonazepam alone or in combination. Improvement of the action myoclonus was observed only after adding levetiracetam. CONCLUSION: Although Lance-Adams syndrome may not be fully curable at this point, levetiracetam appears to be a promising agent that can significantly improve functional level and overall quality of life of patients with this disorder. PMID- 26137723 TI - Polycystic Ovary Syndrome: A Syndrome By Any Other Name. PMID- 26137724 TI - "Heart Bone"--The Case for the IHI Open School as Connector: A Model for Integrating Quality Improvement and Patient Safety into Health Professions Curricula. AB - BACKGROUND: The physician is guardian of the patient and obligated to both the "Science of Medicine" (SOM), defined by the randomized controlled trial, and the "Art of Medicine" (AOM), defined by patient safety (PS) and quality improvement (QI). Historically SOM knowledge has dominated AOM knowledge; however given the frequency of medical harm, a new paradigm is necessary. The Institute for Healthcare Improvement Open School (IHIOS) is accelerating AOM into medical curricula by connecting all stakeholders to the emerging PS and QI sciences, and doing so in an interprofessional manner. METHODS: A South Dakota IHIOS chapter was established in 2011, connecting SOM to AOM knowledge for 600 students from eight schools and thirteen disciplines. Four specific foci included 1) interprofessional pilot project introducing PS and QI into first year curricula, 2) sessions for third-year medical students to assess Open School courses through faculty-facilitated small groups, 3) development of longitudinal quality and safety curricula, 4) integration of OS courses across South Dakota health professions schools. RESULTS: The interprofessional pilot project demonstrated significant learning in 16 of 16 and 13 of 16 (p = 0.05) teaching points. The third-year sessions showed that PS and QI topics are viewed as important especially with faculty-facilitated case studies. Subsequently a longitudinal PS and QI curriculum was implemented. This led to the incorporation of IHIOS courses as core curricula in four South Dakota colleges and eight health disciplines. CONCLUSIONS: Our work was one of the first large-scale efforts to measure learning via the IHIOS through the novel use of the chapter as connector. The model contributes to national efforts for paradigm change through interprofessional education. PMID- 26137725 TI - Anti-Hu Positive Antibodies and Small Cell Carcinoma: A Single Center Review. AB - INTRODUCTION: Small cell lung cancer (SCLC), having properties of neuroendocrine cells, accounts for a small (15 percent) but significant percent of all newly diagnosed lung cancers and is distinguished from non-small cell lung cancer by its rapid doubling time, high growth fraction and the early development of widespread metastases. Therefore, investigation into early diagnosis and treatment is crucial. One sequela of SCLC is a paraneoplastic neurological syndrome usually mediated by a high titer of anti-Hu antibodies, a disease which can present in several variations of paraneoplastic encephalomyelitis. The presence of anti-Hu antibodies in patient serum, even at a low titer, may serve as a diagnostic marker for SCLC and as a model for antibody-based early cancer detection. Furthermore, anti-Hu titers may eventually function as a prognostic indicator and trending titers may be a way to monitor treatment of SCLC and associated paraneoplastic syndromes. METHODS: In this retrospective chart review from a single hospital, we review all patients who had positive anti-Hu antibodies and discuss level of titers at diagnosis, outcomes, and length of survival. RESULTS: We describe three cases of positive anti-Hu antibodies and document their diagnosis of SCLC and outcomes. CONCLUSIONS: Anti-Hu antibodies can be used as a diagnostic tool for aiding in the diagnosis of SCLC. Anti-Hu antibodies may be able to be followed as a marker of progression of the disease. PMID- 26137726 TI - Polycystic Ovarian Syndrome: A Primer. AB - Polycystic ovary syndrome (PCOS) affects 8-10 percent of reproductive-aged females, making it the most common state of endocrine dysfunction in women. Patients with PCOS are often treated for the signs and symptoms of the condition without consideration for the underlying syndrome, causing frustration for many affected patients. Abnormal uterine bleeding, endometrial hyperplasia and cancer, hirsutism and other skin changes, obesity, glucose intolerance, hypertension, and hyperlipidemia often accompany the syndrome, making it imperative to address these issues. The keys to diagnosis and treatment are understanding the diagnostic criteria of hyperandrogenism, ovulatory dysfunction, polycystic ovaries and the metabolic syndrome, while aiming treatment at controlling the symptoms and causes of the syndrome. In 2013, the Endocrine Society released its clinical guidelines, Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline. This gives clear diagnostic criteria, and treatment goals aimed at the etiology of the syndrome: to decrease hyperandrogenic symptoms, management of underlying metabolic abnormalities, prevention of endometrial hyperplasia and carcinoma, and improvement of ovulation. PMID- 26137727 TI - Urine Drug Screens: Common False Positives and Negatives. PMID- 26137728 TI - Extenuating Circumstances: The Winter's Tale: Dr. Brown and The Typhoid Epidemic of 1885. PMID- 26137729 TI - DAKOTACARE Update: Health Care Quality. Part 2: Diabetes Care. PMID- 26137730 TI - Patient Education: Short of Breath in the Night. PMID- 26137731 TI - Quality Focus: Progress Report. PMID- 26137732 TI - Dermatopathology for fun and profit: "Updiagnosing" distresses and endangers patients and abuses their t. PMID- 26137733 TI - Acne therapeutics: a closer look at benzoyl peroxide. PMID- 26137734 TI - TrichoScan findings in patients with effluvium capillorum. AB - Effluvium capillorum is a form of nonscarring alopecia characterized by diffuse hair shedding. This condition occurs when the normal balance of hairs in growth and rest phases is disrupted. Trichoscan is a computerized program used for digital measurement of hair growth and hair loss. This study was performed to describe the TrichoScan as a method, which combines standard epiluminiscence microscopy with automatic digital image analysis for the measurement of human hair. The study included 30 patients with effluvium capillorum (16 women and 14 men). A control group consisted of 30 generally healthy patients (14 women and 16 men). For the measurement of hair density and anagen/telogen ratio, a commercially available software (TrichoScan) was used. The results of digital image analysis from the patients showed a highly increased proportion of telogen hair roots. The authors' results indicate that TrichoScan represents a very useful tool in the evaluation of hair loss. PMID- 26137735 TI - Chondroid syringoma: report of four cases. AB - Chondroid syringomas or mixed tumors of the skin are relatively rare adnexal tumors constituting 0.01% to 0.1% of all primary skin tumors. The majority of chondroid syringomas occur at the head and neck region (80%). Their clinical presentation is not specific and the final diagnosis is based on histopathologic examination. The authors report four cases of benign chondroid syringoma in three women and one man aged 26, 45, 50, and 38 years, respectively. They presented with a slow-growing, painless and firm subcutaneous nodule measuring between 1 and 3 cm involving the lower eyelid, the nasogenien groove, the nose, and the chin, respectively. All patients underwent uneventful surgical excision of the nodules. Histologic examination of the surgical specimen was compatible with benign chondroid syringoma in all cases. Chondroid syringomas must be considered in the differential diagnosis of any small subcutaneous nodule in the head and neck region in middle-aged patients. The treatment of choice is total excision, with wide disease-free margins, to rule out malignancy and reduce the risk of recurrence and malignancy in the future. PMID- 26137736 TI - A practical method to detect mycoses of the nails. AB - The authors present a method that allows for reliable identification of fungal structures in nails with suspected colonization by fungi. The method is based on the well-known technique of heating nail fragments in 20% potassium hydroxide, but its details allow for reliable and quick processing of samples, when convenient. The method requires simple equipment and is designed for individual practices but might be employed as is or with minor technical improvements by a dermatology department. Minor changes will make it feasible to simultaneously process several samples. The results that were obtained show that while experienced clinicians achieve positive clinical diagnoses in the majority of instances, inaccuracies occur in a sizable proportion of cases. In addition, the varied combination of yeasts and hyphae that were found, bolster the view that microscopic examination is necessary to justify and optimize systemic treatment of mycoses of the nails. Our technique permits the processing and observation of the totality of samples obtained from a single nail or several nails. PMID- 26137737 TI - Staphylococcus aureus and the skin: a longstanding and complex interaction. AB - Staphylococcus aureus is a leading cause of human bacterial infection, most notable for its ability to infect any tissue in the human host. Among the most common sites of S aureus infection is the skin, predicated by the existence of this organism as a part of the commensal flora in up to half of the population. While the molecular mechanisms by which S aureus adapts to the ecologic niche of the skin and transitions to cause both skin infection and more severe invasive disease are incompletely defined, these represent an exciting and rapidly moving area of research. The ultimate goal of these investigations is to understand human disease pathogenesis, define host susceptibility factors that predispose to colonization and infection, and utilize this knowledge to inform the strategic development of novel preventive and therapeutic strategies. PMID- 26137738 TI - Alopecia areata--Part II: diagnosis and pathology. AB - Alopecia areata is characterized by the abrupt appearance of round or oval, non scarring, flat, single or multiple areas of alopecia, which may coalesce forming large patches of alopecia. The diagnosis is usually clinical but there are important differentials and dermatopathology may help in this definition. PMID- 26137739 TI - Scabies: too late? No, checkmate. PMID- 26137740 TI - BRAF inhibitor-induced neutrophilic dermatoses: a bitter-"sweet" scenario. PMID- 26137741 TI - Pitfalls in diagnosing fragrance allergy. PMID- 26137742 TI - North American Clinical Dermatologic Society 55th annual meeting: Panama City, Panama and Havana, Cuba. PMID- 26137743 TI - An unusual case of Darier disease complicated with a parasitic infestation. AB - A 40-year-old woman living in the countryside near Cali, Colombia, presented with exacerbation of papules located on her face and neck and an ulcer located on the left retroauricular area of 2 weeks' duration. She stated that her skin lesions appeared erratically, beginning at 13 years of age and that her father and daughter had similar skin lesions. Physical examination revealed multiple erythematous, hyperkeratotic papules, and yellowish brown crusts that coalesced to plaques located on symmetrical areas of the forehead, neck, and periauricular areas with excoriation and malodor (Figure 1a and 1b). There were flat-topped papules on the dorsal aspect of her hands. The fingernails exhibited subungual hyperkeratotic fragments, V-shaped notches at the free edges of some nails, distal onycholysis, and white longitudinal bands (Figure 1c). We also discovered a foul-smelling left retroauricular cavity, approximately 3 cm in length and 3 cm in depth, with multiple fly larvae inside of it (Figure 2). We made the diagnosis of retroauricular myiasis and obtained skin biopsy specimens from her forehead and scalp, to confirm the presumptive diagnosis of Darier disease. PMID- 26137744 TI - Cutaneous hyperneury: a new entity or an atypical cutaneous manifestation of MEN 2B? AB - A 33-year-old healthy woman with a family history of hyperlipidemia presented with asymptomatic skin-colored yellowish linear transverse plaques and papules on the trunk and forearms for a period of 6 months (Figure 1). She noticed that the lesions during this period have been gradually increasing in size and number. The initial clinical impression was eruptive xanthomas. A serum lipid profile showed a total serum cholesterol level of 406 mmol/L (high-density lipoprotein, 1.38 mmol/L; low-density lipoprotein, 2.73 mmol/L) and a triglyceride level of 1.1 mmol/L, which is within the normal range. A 4-mm punch biopsy was performed from the skin lesion on the patient's forearm, and findings showed the presence of bundles of mature nerve fibers in the papillary dermis (Figure 2) with a normal overlying epidermis. No abnormalities were seen in the subcutaneous tissue. There was no evidence of lipid deposition. A diagnosis of cutaneous hyperneury was made. PMID- 26137746 TI - Use of blogging in telemedicine: introduction to an Internet-based teledermatology application. PMID- 26137745 TI - Generalized eruptive keratoacanthoma of Grzybowski. AB - A 51-year-old otherwise healthy farmer presented with a 1-year history of numerous extremely itchy bumps on his skin. The lesions came in crops, were pinhead-sized, and subsequently enlarged to form nodules of varying sizes. There was no history of ocular or mucosal involvement or of spontaneous healing of any of the lesions. His medical history was unremarkable. There was neither any family history of similar illness nor any personal or family history of atopy or malignancy. He was previously treated with potent topical steroids and antihistamines without any appreciable benefit. PMID- 26137747 TI - Fixed-drug reaction secondary to cocaine use. PMID- 26137748 TI - Subungual black onychomycosis and melanonychia striata caused by aspergillus niger. PMID- 26137749 TI - Growing a Medical School at Brown: Dr. Aronson's recollections. PMID- 26137750 TI - Evidence appraisal of Owens PL, Barrett ML, Raetzman S, Gibbons MM, Steiner CA. Surgical site infections following ambulatory surgery procedures.: JAMA. 2014;311(7):709-716. PMID- 26137751 TI - Understanding Differing Viewpoints on Preadmission Bathing and Cleansing: Soap vs CHG. PMID- 26137752 TI - Guideline Summary: Cleaning and Care of Surgical Instruments. PMID- 26137753 TI - Eliminating lateral violence among perioperative nurses. PMID- 26137754 TI - Action needed to stop lateral violence in the perioperative setting. PMID- 26137755 TI - New radiation safety guideline to be released. PMID- 26137756 TI - CPC: One Member's Perspective. PMID- 26137757 TI - Role of Esmolol in Perioperative Analgesia and Anesthesia: A Literature Review. AB - Use of opioids to provide adequate perioperative analgesia often leads to respiratory depression, nausea, vomiting, urinary retention, pruritus, and opioid induced hyperalgesia, with the potential to increase length of stay in the hospital. In an effort to reduce perioperative opioid administration yet provide appropriate pain relief, researchers began to study the use of esmolol beyond its well-known cardiovascular effects. Perioperative esmolol has been shown to reduce anesthetic requirements, decrease perioperative opioid use, decrease the incidence of postoperative nausea and vomiting, lead to an earlier discharge, and increase patient satisfaction. This article provides a review of the literature on the use of esmolol as an adjunct for perioperative analgesia and anesthesia. PMID- 26137758 TI - Identification of a Very High Cuff Pressure by Manual Palpation of the External Cuff Balloon on an Endotracheal Tube. AB - The most common complication due to intubation is a high cuff pressure. A high cuff pressure can cause postanesthetic tracheal mucosal injuries in patients undergoing surgery. The aim of this cross-sectional study was to describe whether anesthetic nurses and anesthesiologists identified a very high cuff pressure by manual palpation of the external cuff balloon on an endotracheal tube. An airway device was intubated with an endotracheal tube cuffed to 95 cm H2O. Each participant palpated the external cuff balloon and then filled out a questionnaire, including estimation of the cuff pressure and user frequency of the cuff pressure manometer. The results showed that 89.1% estimated that the cuff pressure was high. Among the participants who rated the cuff pressure as high, 44.8% rated the pressure as quite high and 60.6% rated the pressure as very high. There was no significant relationship between profession and skill in identifying a very high cuff pressure (P = .843) or between work experience and skill in terms of identifying a very high cuff pressure (P = .816). These findings indicate that 10% of patients are at risk of tracheal erosion because of a high cuff pressure. PMID- 26137759 TI - Healthcare Utilizing Deliberate Discussion Linking Events (HUDDLE): A Systematic Review. AB - The phenomenon, "huddle moments," can be described as a preparatory briefing among healthcare providers for the purpose of collaborating, exchanging information, and bringing awareness to patient safety concerns. A historical background of huddle communication is described and a systematic literature review was conducted on preoperative briefing and huddle communication. The article also describes a need for increased interprofessional collaboration education in anesthesia and a need for leadership to support initiatives that improve patient safety. The purpose of this article is to provide a systematic review of huddle communication and give future evidence-based recommendations on how the huddle can be used in healthcare as well as how to roll out use of the HUDDLE acronym: Healthcare, Utilizing, Deliberate, Discussion, Linking, Events. PMID- 26137760 TI - Anesthesia Information Management Systems: An Underutilized Tool for Outcomes Research. AB - Perioperative outcomes research using anesthesia information management systems (AIMS) is an emerging research method that has not been comprehensively reviewed. This review reports an initial analysis of the use of AIMS for perioperative patient outcomes research from articles published between January 1980 and January 2013. Perioperative patient outcomes research based on AIMS has increased greatly since 2001. Although risk stratification studies involving large study populations were most commonly reported, AIMS were also used to report a rare life-threatening anesthesia-related complication, malignant hyperthermia. Use of AIMS for perioperative outcomes research can address clinically relevant topics that traditional research methods have been unable to adequately address, mainly because of the innate challenges presented by perioperative anesthesia practice. It is expected that perioperative effectiveness and outcomes research using large AIMS databases will be more widely embraced in the future to generate useful evidence and knowledge to improve anesthesia care. PMID- 26137761 TI - Implementation of Mass Transfusion Protocol in the Outpatient Operating Room Setting: A Case Study. AB - The current definition of massive transfusion is replacement of 5 U of packed red blood cells in 3 hours because of uncontrolled hemorrhage or replacement of the entire blood volume within a 24-hour period. The prompt activation of a transfusion protocol can quickly restore hemodynamic stability. Effective teamwork and communication is critical for a favorable patient outcome. This case study demonstrates the effectiveness of using a massive transfusion protocol in an outpatient setting. PMID- 26137762 TI - Low-Flow Anesthesia, Low Fresh Gas Flow, and Oxygen Flush: An Interesting Interplay. AB - Identification and analysis of critical respiratory alarms during use of an advanced anesthesia workstation is essential in the intraoperative period. We present and discuss a scenario in which there was activation of a fresh gas flow alarm during low-flow anesthesia intraoperatively and use of oxygen flush to counteract it led to a diluted concentration of the inspired anesthetic agent. PMID- 26137763 TI - Does Moral Distress Differ Between California Certified Registered Nurse Anesthetists in Independent Versus Medically Supervised Practice: An Exploratory Study. AB - The purpose of this exploratory, descriptive study was to determine if moral distress levels differed between certified registered nurse anesthetists (CRNAs) working in medically supervised versus independent practice in California. A 63 question survey was administered to 1,190 California CRNAs. Moral distress was measured by the included Ethics Stress Scale. The response rate was 14.7%, yielding demographic and Ethics Stress scores for 175 respondents. Sixty-five participants answered an open-ended question about moral distress yielding qualitative data. Medically supervised CRNAs had a lower mean moral distress scores (176.8) versus independent practice CRNAs (187.8) (p = .002). Lower scores on the ESS indicate higher moral distress. Qualitative data demonstrated that CRNAs experienced moral distress in the following situations: when pressured to give anesthesia to unoptimized patients, when differences of opinion regarding anesthetic plans occurred, in dealing with end-of-life issues, when working with incompetent providers, and during interprofessional struggles between CRNAs and anesthesiologists. In order to reduce moral distress among CRNAs, implications for practice include increased administrative support, increased communication and reciprocated collegial respect between anesthesiologists and CRNAs, and CRNA representation on ethics committees. PMID- 26137764 TI - Venous Thromboembolism: New Concepts in Perioperative Management. AB - Venous thromboembolism (VTE) is a serious pathophysiologic condition that is a major cause of morbidity and mortality, especially during the perioperative period. A collective term, VTE is used to describe a blood clot that develops inside the vasculature and results in a deep vein thrombosis (DVT) and/or a pulmonary embolism (PE). Deep vein thrombosis and PE are the third leading cause of cardiovascular mortality, superseded only by myocardial infarction and stroke. Patients who receive treatment for acute PE are 4 times more likely to die of a recurrent VTE within the next year. In hospitalized patients who have had surgery, the incidence of VTE and PE is estimated to be 100 times more prevalent than in the general population. The Joint Commission has established Surgical Care Improvement Project measures to address prophylactic interventions to minimize the incidence of VTE. This journal course will review the current approaches to pharmacologic and nonpharmacologic prevention and management of VTE during the perioperative period. Identification and treatment of deep vein thrombosis and acute PE are also described. PMID- 26137765 TI - [Uterine leiomyoma and fibroleiomyoma: treatment for non-pregnant women ]. PMID- 26137766 TI - [THE FIRST EPIDEMIOLOGICAL DATA ABOUT THE HR-HUMAN PAPILLOMA VIRUS TYPES IN SOUTH AND NORTHERN BULGARIA]. AB - The aim of our study were to evaluate the prevalence of HR-HPV infection in women between 15 and 55 years of age in the South and Northern Bulgaria. We have analyzed the HPV status (using DNA-sorb-AM nucleic acid extraction kit) in cervical samples collected during a 3 year period (2010-2012) from 1020 women, aged 15-55 and divided in four age groups, who attended their gynecologists for HPV-DNA cervical test. The rate of the HR-HPV infection was established to be 39.9%. HR-HPV negative were 60.1% of the evaluated subjects. The most commonly isolated genotype in all 407 (100%) infected women was HPV 16 - 190 women (46.7%), followed by HPV 56 - 78 (19.1%), HPV 31- 48 (11.8%) and HPV 33 - 45 (11.1%). To our knowledge, this is the first survey evaluating the prevalence of HR-HPV infection in the South and Northern regions of Bulgarian towns and drawing attention to the unusually high proportion of different HR-HPV. PMID- 26137767 TI - [AN HPV-ASSOCIATED DISEASES AND CERVICAL CANCER AND PROPHYLACTIC HUMAN PAPILLOMAVIRUS (HPV) VACCINES]. AB - Human papillomavirus (HPV) infection is the central cause of invasive cervical cancer (ICC) and its precursor lesions. Both vaccines can prevent most cases of cervical cancer. In addition, both can prevent vaginal and vulvar cancer in women, and HPV-related cancers. HPV4 can prevent genital warts in women and men. Routine vaccination of 12-year-old girls with HPV4 vaccine appears to be cost effective in addition to providing both short-term and long-term health gains. PMID- 26137768 TI - [SERUM HEPCIDIN LEVELS IN ENDOMETRIOSIS]. AB - OBJECTIVE: Endometriosis is a benign disease, which ranks third in mortality from gynecological morbidity after inflammatory conditions and myoma. We tried to evaluate serum iron and hepcidin levels and seek their connection with the development of endometriosis. METHODS: For quantification of serum hepcidin we use ELISA method. 53 women were included, average age 25.4 +/- 4.3. They were divided into two groups--women with endometriosis (EM) and a control group. Samples were taken at the University hospital "Maichin dom" for a period of one year. We measure serum iron, ferritin and calculate transferrin saturation. We use the Pearson's correlation and Student's t-test for evaluating of statistical significance. RESULTS: We found statistically significant differences in serum hepcidin levels in the groups included: women with endometriosis have higher concentrations 64.3 +/- 7.8 MUg/L compared to the control group 19.4 +/- 4.1 MUg/L (r = -0.201, P < 0.001). Serum ferritin levels showed significant differences between the two groups in EM 17.9 +/- 8.4 ng/ml vs control 79.5 +/- 14.6 ng/ml (r = -0.249, P < 0.001). Statistically significant difference was found in serum iron levels: in EM 21.9 +/- 3.2 MUmol/L compared to 13.5 +/- 1.9 MUmol/L in the control group (P < 0.001). CONCLUSION: Our results support the idea that iron overload and increased serum levels of hepcidin plays an important role in the pathogenesis of endometriosis. PMID- 26137769 TI - [SURGICAL TREATMENT OF NON-ENDOMETROID ENDOMETRIAL CANCER]. AB - A research about the incidence rate of extrauterine dissemination- lymph node metastases and positive peritoneal cytology in non-endometroid endometrial cancer (type 2) has been conducted and factors determining this dissemination hystological subtype and depth of myometrial invasion have been evaluated, as well. PMID- 26137770 TI - [Ovarian carcinoma - current treatment, survival and prognosis. Plenary lecture]. PMID- 26137771 TI - [OVARIAN CANCER RECURRENCES IN PARAAORTIC LYMPH NODES]. AB - The authors'surgical experience on 14 patients with ovarian cancer recurrences in paraortic lymph nodes --infrarenal and suprarenal-celiac and triad, were presented. Complete cytoreduction was achivied in all recurrent patients (no visible tumor). The median time to recurrence was 16,5 months (from 10 to 36 months). The median operating time was 90 min (range from 30 to 120 min). The median blood loss was 200 ml (from 100 to 300 ml.). No intra- or postoperative complications were noted. The median postoperative period was 5 days (from 4 to 6 days). PMID- 26137772 TI - [Characteristics of postpartum thyroid dysfunction]. AB - INTRODUCTION: The risk factors and mechanisms for the development of postpartum thyroid dysfunction have been widely discussed. However data on patients suffered spontaneous or induced abortion during early pregnancy are scarce. OBJECTIVE: To reveal the characteristics of thyroid dysfunction in women after an abortion in the first trimester of pregnancy. PATIENTS AND METHODS: A total of 28 women (18 euthyroid, 10 with thyroid dysfunction), mean age 30.46 +/- 1.01 years following abortion in the first trimester have been included in the study. Thyroid stimulating hormone (TSH), free triiodthyronine (FT3), free thyroxine (FT4), thyreoglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb) were measured and ultrasound assessment of the thyroid was performed 3 and 9 months after the interruption of pregnancy. RESULTS: Hypothyroidism was found in 6 of the women with thyroid dysfunction and thyrotoxicosis--in 4. Clinical features of thyroid dysfunction were observed in 3 patients while in the remaining 7 cases, diagnosis was made on the basis of hormonal levels. Positive titers of thyroid autoantibodies were detected in the majority of the cases with functional disordes. In 6 patients thyroid dysfunction was transient and in 4 hormonal abnormalities persisted on by the 9th month after the abortion. The comparative analysis showed that the volume of the thyroid gland and the degree of hypoehogenicity were significantly higher in patients with thyroid dysfunction compared to euthyroid women. CONCLUSION: Thyroid dysfunction after abortion in the first trimester is mainly of autoimmune pathogenesis and its characteristics do not differ from those of postpartum thyroiditis. In the majority of patients these disorders are subclinical and may remain unrecognized. A close active follow up of patients at increased risk of functional thyroid disorders after an abortion is required in order to prevent morbidity and identify the cases developing permanent thyroid dysfunction. PMID- 26137773 TI - [COMBINED APPLICATION OF FETAL FIBRONECTIN AND INSULIN-LIKE GROWTH FACTOR IN PRETERM DELIVERY DIAGNOSIS--OUR RESULTS]. AB - The insulin-like growth factor IGFBP-1 is a binding protein (IBP-1), also known as placental protein (PP12), is encoded in people as IGFBP-1 gene. The IGFBP-1 is an especially vital hormone in the female reproductive physiology. The presence of it in large quantities in the amniotic fluid can be used as a biochemical marker for preterm birth and premature rupture of membranes. Fetal fibronectin is a high-molecular glycoprotein, that is produced during pregnancy and has a role as biological glue, binding the foetus membranes to the endometrium. fFN can be found in the cervicovaginal secretions until 22nd gestational week and later on during the last trimester (1 to 3 weeks before birth). fFN is usually absent between 24th and 34th gestational week. Thirty sixth (30%) of all the 120 females tested had positive fFN test results and were, therefore, at high risk for preterm delivery. Despite the implemented tocolytic therapy, 15 (12.5%) of them delivered before the 37th gestational week. The results from the investigation for the presence of pLGFBP-1 in 120 pregnant women show that 35.8% (43 women) were positive and 15(12,5%) of them delivered before the 37th gestational week despite the implemented tocolytic therapy In both tests, the average gestational age of the premature fetus was 32.5 / 2.8 gestational weeks. PMID- 26137774 TI - [CYTOGENETIC ANALYSIS OF PATIENTS WITH PRIMARY AMENORRHEA]. AB - Primary amenorrhea is one of the common reproductive disorder affecting females. It leads to the absence of menarche in the reproductive age group in females and/or complete absence of reproductive organs. The physiology of menstruation and reproduction has a strong correlation with the expression of the X chromosome. Thus, the role of the clinical geneticists in terms of diagnosis, risk assessment, genetic counseling and management of patients with primary amenorrhea and their families is essential. The genetic contribution to amenorrhea is studied both at the cellular and molecular level aiming at chromosomal abnormalities and gene mutations. In the present study we aim to perform chromosomal analysis in 140 patients present with primary amenorrhea employing GTG banding technique. The resulting karyotype revealed 67.4% (n = 95) with normal chromosome composition and 32.6% (n = 46) showed chromosomal abnormalities. In patients with abnormal chromosome constituents, 20% (n = 9) exhibit numerical aberration, 22% (n = 10) showed structural abnormalities, 43% (n = 20) mosaic genotype and 15% (n = 7) of cases--male karyotype. Furthermore, the involvement of Y chromosome and the origin of marker chromosome was confirmed by applying fluorescent in situ hybridization (FISH) in four patients. PMID- 26137775 TI - [NON-HODGKIN'S LYMPHOMA OF THE FEMALE GENITAL SYSTEM--A LITERATURE REVIEW]. AB - Lymphomas are a heterogeneous group of malignant lymph proliferative diseases and represent 3-4% of all neoplastic processes. They are subdivided into Hodgkin's (15%) and non-Hodgkin's (85%). Non-Hodgkin's lymphomas (NHL), depending on their primary location are subdivided into nodal and extranodal. Extranodal forms of NHL represent 25-40% of NHL where only 2% of them concern the female genital system. They develop in the female genital organs primary or secondary invade them. Extranodal NHL genital form is extremely rare and represents 0.5% of all malignant genital diseases. All genital organs may be affected where most lymphomas are localized in the cervix, uterine body and ovary. The clinical picture is nonspecific whichcomplicates the timely diagnosis. A multidisciplinary approach is used for staging of lymph proliferative disease. Treatment of genital form of NHL is determined by the age of the patient and her reproductive intentions, clinical stage, histological variant. Due to the low occurrence there are no widely accepted protocols of behavior and treatment of genital extranodal NHL. The first method of choice is the conservative approach by chemotherapy. The most widely used and most effective is the combination Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP). According to data in the literature the 5-year survival rate for cervical extranodal NHL is 80%. Surgery should not come into consideration when there are certain indications. The aim of this review is to examine rare cases of non-Hodgkin's genital lymphomas in females and to present opportunities for their diagnosis and treatment. PMID- 26137776 TI - [KAPOSI'S SARCOMA OF THE VULVA]. AB - Kaposi's sarcoma represents multiple idiopathic hemorrhagic sarcoma--a mesenchymal tumor that affects the blood and lymph vessels. Its performance is associated with an infection with human herpes virus type 8--the so called KSHV (Kaposi's sarcoma -associated virus), and with the human immunodeficiency virus. Kaposi's sarcoma is considered as a typical clinical manifestation in male homosexuals suffering from acquired immune deficiency syndrome (AIDS), while his performance in HIV-positive women is unusual, with a ratio of men to women--10 15: 1. Vulvar localization is much rarer. It is up to 5 times more frequent in HIV- positive patients. It is clinically represented in most of the cases by the clinical picture of nonspecific tumor mass. Biopsy and further virological testing for establishing KSHV in lesional tissue is essential for confirming the diagnosis. Serological testing for HIV/AIDS in affected patients is required. Local treatment includes surgical excision of solitary lesions, cryotherapy as well as radiotherapy. The use of interferon alpha resulted in complete remission in approximately 40% of the affected patients. New trends in treatment tend to be pathogenetically directed as in the process of studies to date are inhibitors of angiogenesis. Due to the rarity of the occurrence, non-specific clinical picture and histological findings, Kaposi's sarcoma should be considered in the differential diagnosis of tumor masses with vulvar localization, especially in HIV-positive patients. PMID- 26137777 TI - [MALIGNANT LYMPHOMAS OF THE VULVA- DIAGNOSIS AND THERAPY]. AB - Primary malignant lymphomas affecting the female reproductive system are unusual, accounting for about 30% of all lymphomas. The majority of them are represented by non-Hodgkin lymphomas (over 90%), as their location most commonly involved the ovarian (49%), followed by the uterus (29%), fallopian tubes (11%), vagina (7%), and only in 4% of the cases, the primary lymphomas affecting the vulva. Although rare, lymphomas of the vulva are characterized by high proliferative potential, aggressive clinical course and poor prognosis and may lead to rapid vulvar and perineal destruction. Due to the rarity of their occurrence in the vulvo-vaginal area and their non-specific clinical manifestations, lymphomas with such location are often a diagnostic challenge and require a wide range of differential diagnoses. We present the epidemiological structure, the clinical and immunohistochemical markers characteristic of the most common lymphomas with vulvar localization, in order to emphasize their role in the differential diagnosis of vulvar tumor masses. PMID- 26137778 TI - [PROLONGED RETAINED PLACENTA ACCRETA IN THE UTERUS AFTER VAGINAL DELIVERY (A CASE REPORT AND REVIEW OF LITERATURE)]. AB - A case of prolonged retention in the uterus of placenta accreta after vaginal delivery is reported in the paper. The patient was 20 years old G3, P0 with two pregnancy terminations on request. She was admitted to the obstetric department of a regional hospital one day after the EDD with irregular contractions and non reassuring CTG. A few hours later intrauterine fetal demise occurred. Spontaneous labor commenced and a stillborn growth retarded fetus was delivered. Methergin was administered during the third stage of labor, but the placenta was not separated even after repeated Crede maneuvers, the last one under anesthesia. Since cervical spasm was present, the attempts for manual or instrumental separation of the placenta were unsuccessful. There was no genital bleeding, so further conservative approach was followed including continuous IV infusion of uterotonics, combined antibiotic therapy, close observation of the vital signs and the laboratory indicators. Three days after delivery the patient was transferred to a University Hospital because of subfebrile temperature. Her general condition on admission, although subfebrile, was good, there was no genital bleeding, the cervix was closed. The subfebrile temperatrure persisted despite antibiotic treatment; CRP was elevated (51,9 mg/l.). Because of suspicion for endomyometritis, on day 8th after delivery instrumental extraction of the placenta was undertaken with preparedness for hysterectomy in case of need. Although the procedure was difficult, with the placenta being extracted in parts, bleeding was scarce. The post operative period was uneventful and the patient was discharged from hospital five days after the intervention. A review of literature on the obstetric management of cases with retained placenta accreta after vaginal delivery is presented. The existing therapeutic options are discussed including their advantages and complications. PMID- 26137779 TI - [CHRONIC RENAL FAILURE AND PREGNANCY--A CASE REPORT]. AB - Pregnancy in women with chronic renal failure is a complex therapeutic problem requiring a multidisciplinary approach. It is associated with a higher risk of many perinatal complications. The most common abnormalities are related to: progression of renal failure, development of preeclampsia development of nephrotic syndrome, anemic syndrome, IUGR and fetal death. The prognosis depends on the values of serum creatinine prior to pregnancy, the degree of deterioration of renal function, development of additional obstetric complications and the specific etiological reasons that have led to the occurrence of renal failure. Determining the optimum time for authorization birth depends on the condition of the mother, the condition of the fetus and the rate of progression of renal failure, and the deadline the pregnancy should be terminated is 35 weeks. We present a case of a patient with chronic renal failure, with favorable perinatal outcome. PMID- 26137780 TI - [PRENATAL DIAGNOSIS OF FOETAL TRISOMY 3Q WITH PATERNAL ORIGIN]. AB - Balanced chromosomal translocations do not generally have phenotypic manifestation, but lead to increased risk of miscarriage and live-birth of chromosomally unbalanced offspring in carriers. Frequently prenatal diagnosis of an unbalanced translocation may incidentally detect a balanced translocation in the family. Here, we report a unique case of trisomy 3q (karyotype 46,XYder(3)t(3;21)(q11;p11)), detected prenatally due to abnormal findings of the fetus ascertained through ultrasound assessment like growth retardation, vermal agenesis, micrognathia, cystic hygroma of the neck, dextra position of arcus aortae, shorter for the gestational week long bones In order to determine the paternity of this chromosomal aberration, the cytogenetic analyses of the parents was performed. A balanced paternal translocation 46,XY,t(3;21)(q11;p11) wase identified. During the next pregnancy the same balanced translocation of paternal origin wase also identified. This case demonstrate the significance of prenatal ultrasound screening of the fetus; the necessity of cytogenetic analysis of a fetus with prenatal ultrasound abnormalities; genetic counseling of such families with aim of prenatal care and prevention during next pregnancies. PMID- 26137781 TI - [BENIGN OVARIAN PATHOLOGY FINDINGS IN PRE-OPERATIVE AND INTRA-OPERATIVE SIGNS SUGGESTIVE OF MALIGNANCY--CASE SERIES]. AB - Case 1--22 year old patient with dense permagnum adult teratoma, ascites, ipsilateral hydro-ureter and hydro-nephrosis, elevated C -125 level a pseudo- military peritoneal spread. Case 2--19 -year old patient with endometrial kystoma, originating at the uterine fundus with with elevated C-125 levels. Case 3--22 year old patient with monstrous tecoma permagnum, ascites and concomitant pleural effusions as in Meigs syndrome. Case 4--66 year old patient, multiparous with granular cell tumor, recurrent uterine bleeds and endometrial poliposis, with ambiguous C-125 level and congenital uterus bicornis bicolis anomaly. Cases are presented in chronological order, with detailed description and accompanying abundant photo images. PMID- 26137782 TI - [The pharmacotherapy of obesity]. AB - Obesity is considered the most concerning and blatantly visible--yet most neglected--public health problem by the WHO. The steadily increasing number of overweight and obese people has reached 2.3 billion and 700 million worldwide, respectively. Obesity is a complex condition, one that presents serious health risks with respect to type 2 diabetes, ischemic heart disease, and hypertension, therefore controlling the global obesity epidemic decreases not only health problems, but also expenditure. The underlying cause of obesity is a metabolic disorder of genetic, central nervous system or endocrine etiology that manifests in increased nutritional intake and/or decreased physical activity ultimately leading to excessive lipogenesis. The natural treatment of obesity, that is often advised, is comprised of healthy lifestyle choices, namely low-calorie diet and exercise. However, the pharmaceutic treatment of obesity is just as important; having a better compliance rate, anti-obesity drugs also improve quality of life and patient-care outcome concerning accompanying diseases. In most countries only one drug is currently available against obesity: orlistat, which is a specific and irreversible lipase inhibitor. One of the reasons for the scarce number of anti-obesity drugs is the complex pathomechanism involved in obesity. Interference with the intricate biochemical processes that govern alimentation may lead to widespread adverse effects. The advances of the field however, have prompted novel drug leads. In the past few years FDA has approved new drugs for the treatment of obesity, recently liraglutide in 2014. The approval of drug combinations, such as phentermine/topiramate and bupropion/naltrexone are also noteworthy, the components of which have been previously approved, but not necessarily for obesity as main indication. Furthermore, there are many anti obesity drug candidates currently in clinical phase trials, with promisingly modest adverse effect profiles; hence the expansion of the anti-obesity agents in the near future can be foreseen. The present work summarizes the central and peripheral regulatory pathways of energy consumption, nutrition, and appetite. The possible drug targets, the currently available and novel anti-obesity agents, and the new trends in obesity research are also discussed. PMID- 26137783 TI - [Investigation of permeability of intranasal formulations using Side-Bi-Side horizontal diffusion cell]. AB - Nowadays the nasal route has received a great attention as a reliable administration for the systemic administration. In the Department of Pharmaceutical Technology, University of Szeged, the main research work is the design and development of innovative nasal formulations, which can open new possibilities for some well-known agents and may also help some drug-candidates delivery problems. The aim of this work was to present some reliable models for investigation of permeability, such as Spectra/Por Dialisys Membran, ZelluTrans/Roth Mini Dialyzer, MUFLUX diffusion Cell, Navicyte Vertical and Horizontal Diffusion Chamber System and In-line Cell. In addition, the horizontal membrane diffusion model (Side-Bi-Side) was used to investigate in vitro and ex vivo studies of permeability of meloxicam in comparison with the vertical diffusion cell (Franz). The present study investigated the meloxicam in different dosage forms (powder, spray, gel). It was found that the Side-Bi-Side cell is suitable to test the nasal formulations, but the uniform distribution of the active substance cannot be ensured in donor place by increasing the viscosity of the compositions, therefore the Franz cell is recommended for investigation of nasal gel. Previous measurement cannot be found related to this topic. PMID- 26137784 TI - [Occurence of diarylheptanoids in Corylus species native to Hungary]. AB - Since the last decade naturally occurring diarylheptanoids have been in the focus of scientific interest due to their various. beneficial biological effects. Besides the outstanding importance of the curcuminoids isolated from members of the Curcuma genus (Zingiberaceae), several different diarylheptanoids identified in Alnus species (Betulaceae) have been proved to possess notable pharmacological effects. Chemoprotective, neuroprotective, hepatoprotective, antiviral, antibacterial, antiinflammatory and antioxidant activities suggest their potential role in clinical practice. The aim of our study was the phytochemical investigation of the Corylus (Betulaceae) species native to Hungary: the Common hazel (Corylus avellana L.), the Turkish hazel (Corylus colurna L.) and the Filbert (Corylus maxima Mill.) in order to characterise their phenolic-profile. Although these plants have been used in traditional medicine for long time, literature data regarding their phytochemical composition is limited to the flavonoid and hydroxycinnamic-acid derivatives of C. avellana leaves. No previous studies have been published reporting the presence of diarylheptanoid compounds in any of the Corylus species. Soxhlet extraction with solvents of increasing polarity was performed on the bark and leaves of the mentioned three Corylus species. The phenolic-profile of the methanolic and ethyl acetate extracts was investigated by HPLC-DAD-ESI-TOF-MS and HPLC-DAD-ESI-MS/MS methods. Altogether 37 different phenolic compounds were detected in the extracts: twenty diarylheptanoids (1-20), nine flavonols (21-29) and eight other phenolics: caffeic and quinic acid derivatives and flavanones (30-37). The main compounds of the extracts were identified as myricetin- quercetin- and kaempferol-3-O rhanmosides. PMID- 26137786 TI - Evaluation of efficacy and effectiveness of live attenuated zoster vaccine. AB - Herpes zoster (HZ) is a viral disease characterized by a dermatologic and neurologic involvement caused by the reactivation of the latent varicella zoster virus (VZV) acquired during primary infection (varicella). HZ incidence increases with age and is related to waning specific cell-mediated immunity (CMI). The most frequent complication of HZ is post-herpetic neuralgia (PHN) characterized by chronic pain lasting at least 30 days, with impact on patients' quality of life. Available treatments are quite unsatisfactory in reducing pain and length of the disease. The evaluation of the epidemiology, the debilitating complications (PHN), the suboptimal available treatments and the costs related to the diagnosis and clinical/therapeutic management of HZ patients have been the rationale for the search of an adequate preventive measure against this disease. The target of this intervention is to reduce the frequency and severity of HZ and related complications by stimulating CMI. Prevention has recently become possible with the live attenuated vaccine Oka/Merck, with an antigen content at least 10-fold higher than the antigen content of pediatric varicella vaccines. Clinical studies show a good level of efficacy and effectiveness, particularly against the burden of illness and PHN in all age classes. Accordingly to the summary of the characteristics of the product the zoster vaccine is indicated for the prevention of HZ and PHN in individuals 50 years of age or older and is effective and safe in subjects with a positive history of HZ. PMID- 26137787 TI - Staphylococcus aureus with reduced susceptibility to vancomycin in healthcare settings. AB - Glycopeptide resistance in Staphylococcus aureus is a source of great concern because, especially in hospitals, this class of antibiotics, particularly vancomycin, is one of the main resources for combating infections caused by methicillin-resistant Staphylococcus aureus strains (MRSA). Reduced susceptibility to vancomycin (VISA) was first described in 1996 in Japan; since then, a phenotype with heterogeneous resistance to vancomycin (h-VISA) has emerged. H-VISA isolates are characterised by the presence of a resistant subpopulation, typically at a rate of 1 in 10(5) organisms, which constitutes the intermediate stage betweenfully vancomycin-susceptible S. aureus (VSSA) and VISA isolates. As VISA phenotypes are almost uniformly cross-resistant to teicoplanin, they are also called Glycopeptides-intermediate Staphylococcus aureus strains (GISA) and, in the case of heterogeneous resistance to glycopeptides, h-GISA. The overall prevalence of h-VISA is low, accounting for approximately 1.3% of all MRSA isolates tested. Mortality due to h-GISA infections is very high (about 70%), especially among patients hospitalised in high-risk departments, such as intensive care units (ICU). Given the great clinical relevance of strains that are heteroresistant to glycopeptides and the possible negative impact on treatment choices, it is important to draw up and implement infection control practices, including surveillance, the appropriate use of isolation precautions, staff training, hand hygiene, environmental cleansing and good antibiotic stewardship. PMID- 26137788 TI - Surveillance of adverse events following immunization with meningococcal group C conjugate vaccine: Tuscany, 2005-2012. AB - INTRODUCTION: Post-licensure vaccine safety studies are essential to identify uncommon events that may be difficult to assess during pre-licensure studies. The aim of our study was to evaluate the safety of serogroup C meningococcal conjugate (MCC) vaccine in Tuscany from 2005 to 2012. METHODS: All adverse events (AEs) to MCC vaccine notified from 2005 to 2012 were obtained from the regional health authority. RESULTS: Following 451,570 doses administered, 110 suspected AEs were notified (mean annual reporting rate: 2.8/10,000 doses). The most frequently AE reported was fever (60%), followed by swelling at the injection site (11%) and febrile seizures (10%). Overall, 77.3% of cases were not severe, while 21.8% required hospitalization. Almost four months after the receipt of the vaccine, a one-year-old infant was diagnosed with a pervasive developmental disorder with disturbance of speech, but any link with the vaccinations received was refuted. Most AEs (80.9%) occurred after co-administration with other vaccines, especially with MMR or MMRV vaccines (42.7%) or the DTPa-HBV-IPV/Hib vaccine (33.7%). DISCUSSION: Our study confirmed the high level of safety of MCC vaccine in Tuscany: AEs proved rare and all cases had only temporary and self resolving consequences. As usually only the most severe suspected AEs are reported, the true proportion of AEs requiring hospitalization was most probably overestimated, and it is plausible that most of these cases were in fact only temporally related. PMID- 26137789 TI - Logistic regression of attitudes and coverage for influenza vaccination among Italian Public Health medical residents. AB - INTRODUCTION: A few number of literature specifically addresses vaccination uptake among Public Health Residents (PHRs). Influenza vaccine attitudes and risk perceptions of PHRs across Italy were studied, contributing to literature on influenza vaccination uptake predictors, in particular among young physicians. METHODS: An online survey was conducted in 25 Schools of Public Health in Italy in 2011-2012. Results were analysed using prevalence and logistic regression methods. RESULTS: A total of 365 Italian public health residents were included in the study. Vaccination uptake was confirmed by 22.2 and 33.2% of PHRs in 2010 2011 and 2011-2012, respectively. For the 2010-2011 influenza season, vaccination was associated with male sex (adj-OR 3.43; 95% CI = 1.5-7.84) and vaccination history (adj-OR 29.44; 95% CI = 6.4-135.04). For the 2011-2012 season, vaccination was significantly associated with having had between one and three influenza vaccinations in the previous five years (adj-OR 11.56; 95% CI = 6.44 20.75) or more than three (adj-OR 13643; 95% CI = 30.8-604.7) and with individual participation in general population vaccination campaigns (adj-OR 1.85; 95% CI = 1.01-3.41). DISCUSSION: Italian residents in public health have no confidence and a low personal risk perception about vaccinations therefore taking no measures to protect patients, general population and themselves. Annual influenza vaccination acceptance is associated with influenza vaccine uptake in the previous years and personal involvement in general population vaccination campaigns. These factors should be considered for the design of future campaigns targeting public health residents. PMID- 26137790 TI - [Seasonal variations in the lipid profile of apparently healthy young adults living in Santiago, Chile]. AB - The lipid profile is impacted by numerous factors. However, the seasonal variations in this profile have not been well-established in the southern hemisphere. The aim of this study was to determine the seasonal variation of the lipid profile in apparently healthy adults from Santiago, Chile. The study design was observational and prospective, involving 50 healthy volunteers of both genders, aged 23-62 years. The lipid profile was measured at monthly intervals over the course of one year. LDL was significantly higher in winter -spring than in summer- fall (p < 0.01). Conversely, HDL decreases significantly in winter (p < 0.05). We conclude that there are seasonal variations in the serum levels of LDL and HDL. The circannual pattern is characterized by increased levels of LDL in winter-spring and low levels of HDL in winter. PMID- 26137791 TI - Urinary iodine excretion in healthy Mexican adults. AB - The iodine nutritional status of a population is mainly measured by urinary iodine excretion (UI) and thyroid volume determined by ultrasound (US). The surveillance of nutritional iodine levels in the Mexican population has been insufficient. Our aim was to determine the UI in random samples from adults living in an urban area. We selected a sample of healthy individuals over the age of 18 that were students, physicians or administrative personnel at our Institution and had no known thyroid disease. Thyroid volume was determined by ultrasound in all volunteers as well as thyroid hormones and antithyroid antibodies and a urine sample was obtained. One hundred and two volunteers with a median age of 29, participated in the study. The group's median UI was 221 MUg/L, interquartile range (IQR) (135.0 to 356.8) and no differences were observed between genders: women had a UI of 218.0 MUg/L IQR (129.0 a 351.0) vs. 223.0 MUg/L IQR (138.0 to 374.0) in males, p 0.941. Excessive dietary iodine intake was established in 31.4% of all volunteers according to their UI, placing them at risk of thyroid dysfunction. It is fundamental to evaluate the national iodine nutritional status in Mexico. We discuss the current status of the nutritional state in the Americas, emphasizing that in Latin America and the observed tendency in the region to ingest a diet high in iodine. PMID- 26137785 TI - Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part II: Future compounds against influenza virus. AB - In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential for viral replication and propagation. These latter compounds have been developed quite recently. Among the first group, we will focus especially on hemagglutinin, M2 channel and neuraminidase inhibitors. The second group of compounds may pave the way for personalized treatment and influenza management. Combination therapies are also discussed. In recent decades, few antiviral molecules against influenza virus infections have been available; this has conditioned their use during human and animal outbreaks. Indeed, during seasonal and pandemic outbreaks, antiviral drugs have usually been administered in mono therapy and, sometimes, in an uncontrolled manner to farm animals. This has led to the emergence of viral strains displaying resistance, especially to compounds of the amantadane family. For this reason, it is particularly important to develop new antiviral drugs against influenza viruses. Indeed, although vaccination is the most powerful means of mitigating the effects of influenza epidemics, antiviral drugs can be very useful, particularly in delaying the spread of new pandemic viruses, thereby enabling manufacturers to prepare large quantities of pandemic vaccine. In addition, antiviral drugs are particularly valuable in complicated cases of influenza, especially in hospitalized patients. To write this overview, we mined various databases, including Embase, PubChem, DrugBank and Chemical Abstracts Service, and patent repositories. PMID- 26137792 TI - [Eating habit and metabolic syndrome in a sample of Brazilian adults]. AB - The objective was to analyze indicators related to eating habits and their association with metabolic syndrome (MetS) in a representative sample of adults in a community from State of Sao Paulo, Brazil. The sample was comprised of 1,112 participants aged >= 20 years. Data from sociodemographic issues, indicators regarding eating habits, anthropometric measures, resting arterial pressure, blood glucose and plasma lipids were registered. MetS was assessed according to the NCEP-ATP III criteria. The results showed that adequate consumption of fruits and vegetables was reported by less than 10% of the individuals. Regular consumption of fatty foods (5 days/week) was reported by 54.2% and sugar-added products and soft drinks by 3 8.6% of the interviewees. Gender, age, schooling, socioeconomic level and nutritional status influenced significantly the eating habits. Prevalence of MetS was approximately 24%, significantly higher in men (27.8% vs 20.3%; p = 0.005). Risk to identify MetS in individuals who reported not consuming regularly fruits and vegetables was approximately two times higher than their peers who reported adequate intake (women: OR = 1.93; 95% CI 1.51 - 2.38; men: OR = 2.04; 95% CI 1.63 - 2.40). Exposure risk for MetS was progressively higher according to reported higher consumption of fatty foods, sugar-added products and soft drinks. The findings suggest interventions in order to emphasize healthy eating habits, which could help to minimize risk of MetS. PMID- 26137793 TI - [Intakes of energy and macronutrients in pregnant women in the northeast of Mexico]. AB - Descriptive and transversal study, first to report the dietary intake of energy and macronutrients in pregnant women in the northeast of Mexico. Convenience sample of 125 pregnant women (15-45 years of age) in the third trimester, who were prenatal patients in the Hospital Regional Materno Infantil, Nuevo Leon, Mexico. It was reported the level of studies, marital and professional status, weight, height and body mass index (BMI). Diet was evaluated by 24-hour food recalls, in 3 non-consecutive days. There were analyzed the intake of energy and the percentage contribution of calories from macronutrients according to the recommendations of intake of pregnant women. Intake of energy was 1683,8 Cal/day. The caloric contribution of saturated fat was higher than the recommendation in 53.6% of women. 76.8% of participants ate more than 55% of energy from carbohydrates, while 86.4% ate more sugars than the amount suggested. The median intake of protein was 12.0% of total energy intake. 75% of participants consumed less than 22,5 g of total dietary fiber. The relevance of knowing the intakes of energy and macronutrients in pregnant women may be due to the possible influence of diet over the child's appetite and maternal complications. Results of this study suggest the need to provide women with adequate nutritional recommendations since the first trimester of gestation, according to their nutritional status and social environment. PMID- 26137794 TI - [Evaluation of a nutrition education intervention in teachers and students in pre school and primary schools in los Andes, Chile]. AB - The objective of the study was to assess the impact of a nutrition education program for teachers to improve food knowledge, food consumption and the nutritional status of their pre basic and basic students. A quasi-experimental study was carried out, with a pre-post evaluation of food knowledge, food consumption and nutritional status. The sample was 25 teachers and 465 students in Los Andes, with 352 students as control group in San Felipe. The nutrition intervention consisted in 9 interactive workshops for teachers during 5 months, transferring the information to the students. In the experimental group there was a significant improvement in food knowledge and a decrease in non-healthy food consumption in students, compared with the control group, without changes in nutritional status. In conclusion, the intervention in teachers improved food knowledge and healthy food consumption in students. As a consequence of the short period of intervention, the nutritional status did not change. If these strategies are maintained over time and incorporated to the school curricula could achieve more significant results, in particular if parents are incorporated in school nutrition education programs. PMID- 26137796 TI - [Effect of freezing and cooking on the texture and electrophoretic pattern of the proteins of octopus arms (Octopus vulgaris)]. AB - Texture is the most valuable feature in cephalopods. Factors that mainly affect the texture of octopus are: freezing, scalding and cooking. The aim of this study was to assess the effect of freezing, scalding and length of cooking time on the texture and electrophoretic pattern of proteins of octopus arms. Octopuses were trapped near Margarita Island and carried with ice to the laboratory where they were packed and subjected to: a) freezing at -27 degrees C or at -20 degrees C b) scalding c) cooking for 25 min, 35 min or 45 min. Shear force was determined by Kramer cell on strips of octopus arms. SDS-PAGE was done according to the Laemmli method with 12% polyacrilamide gels. A sensory evaluation of the preference of texture was carried out using a hedonic scale of 7-points and a non-trained panel. Octopus texture was not affected by freezing temperature or scalding. Frozen octopus was softer after cooking than fresh. The longer the cooking time was, the softer the octopus was. Myosin heavy chain (MHC) was not significantly affected by scalding or cooking; however large aggregates heavier than MHC, new bands and loss of resolution of the bands appeared. Myosin and paramyosin bands were more affected by freezing prior to cooking. PMID- 26137795 TI - [Detection of toxigenic genes nheA, nheB and nheC in Bacillus cereus strains isolated from powdered milk samples in Costa Rica]. AB - Powdered milk is a frequently consumed product that does not need to be kept under cold conditions. Nevertheless, different microorganisms may contaminate it. Powdered milk is a highly consumed product by Costa Rican population, and Bacillus cereus is a potentially pathogenic bacteria associated to it, with the ability to develop toxins depending on the presence of the respective codifying genes. The aim of this study was to determine the presence of the toxigenic genes nheA, nheB and nheC from B. cereus strains, found in powdered milk sold at the Costa Rican national market. Five different lots of ten brands of powdered milk, distributed in the metropolitan area of San Jose, Costa Rica were analyzed. B cereus load was quantified using the Most Probable Number technique and identified using the Vitek system. The presence of the toxigenic genes was determined using the PCR technique. The isolation frequency of this bacteria in the powdered milk samples analyzed reached 50%, with populations ranging from 3 to > 100 MPN/g. Five out from nineteen strains were found positive for the three toxigenic genes, indicating contamination with potentially toxigenic B. cereus in powdered milk distributed in the national market, and an important risk for public. health. PMID- 26137797 TI - LATINFOODS activities and challenges during the period of 2009-2012. AB - The Latin American Network of Food Composition Data System (LATINFOODS) is the regional data center of the global network "International Network on Food Data Systems" (INFOODS) co-sponsored by the Food and Agriculture Organization of the United Nations (FAO) and the United Nations University (UNU). The aim of this work is to provide information on the main activities held and challenges during the period 2009- 2012. The activities included: network organization, technological development, research, web site modification, database location, publication of new food composition tables, organization and participation in scientific activities, assistance and training. During this period, new strategic alliances where food composition is key were developed. This promoted more activities and strengthen working links in the region. The main challenges were: 1) to improve and update the regional database 2) to improve the national capacities for generating and compiling data to elaborate and update the national food composition tables 3) to establish and implement the database software in branches; 4) to reach technical and financial sustainability. Despite the fact that the network has a dynamic structure consolidated, trained and experienced members, a database of regional food composition, specialized tools and documents; more support for sustainability and progress is required. PMID- 26137798 TI - How to measure quality of care in patients presenting with STEMI? A single-centre experience. AB - OBJECTIVE: The evaluation of the quality of care delivered to patients with acute coronary syndromes is becoming increasingly important. Due to novel regulations permitting the installation of new catheterization laboratories in Belgium, the Flemish government initiated a project to measure quality of care in patients with an ST-elevated myocardial infarction (STEMI) by measuring four quality indicators: prescription of ACE inhibitor, beta blocker or aspirin on discharge and unadjusted mortality. However, we are not convinced that these four indicators will provide sufficient information on the quality of care in our hospitals. Hence, we performed a retrospective analysis on a larger set of parameters and evaluated their applicability as indicators of quality of care. METHODS: We measured 38 indicators in 153 patients (69 transferred and 84 on site) with a STEMI who presented at, or were transferred to the UZ Brussels in 2013 and received percutaneous coronary intervention (PCI). RESULTS: The unadjusted overall mortality was 7.2% (n = 11/153). Important differences in unadjusted mortality were observed between the on-site and transferred patients (10.7%, n = 9 vs 2.9%, n = 2, P = 0.112), which were attributed to the initial condition at presentation and a larger proportion of cardiogenic shocks in the on site group. Discharge medication highly corresponded with the ESC guidelines. CONCLUSION: We demonstrate that the proposed quality indicators do not provide sufficient information to compare hospitals and that it is of utmost importance to weigh the mortality according to risk profile. PMID- 26137799 TI - Recanalization of arterial duct is feasible, effective and its potential risks are treatable. AB - BACKGROUND: Recanalization of arterial duct (AD) is rarely needed. OBJECTIVE: The aim of this study is to report our experience regarding the feasibility and effectiveness of arterial duct recanalization in three infants and review the relevant literature. METHODS AND RESULTS: We report on three patients with decreased pulmonary blood flow after initial palliation. The first patient had pulmonary atresia (PA) and an intact ventricular septum. He needed recanalization of the AD after pulmonary valve perforation and dilatation. The second patient had PA and ventricular septal defect (VSD). His AD originated from the left subclavian artery. He required AD recanalization after palliation with a central shunt and clipping of the duct. During intervention he developed a thrombus in the stent, which was treated successfully using thrombolytic treatment. The third patient had PA and VSD. The arterial duct originated from the left subclavian artery and was recanalized after spontaneous closure despite prostaglandin infusion. During the procedure the patient had severe desaturation and bradycardia requiring resuscitation fortwo minutes. All infants had successful arterial duct recanalization and stenting. Additionally, they were clinically stable during follow-up. CONCLUSION: Arterial duct recanalization and stenting is a feasible and effective procedure in selected cases, and its risks are treatable. Long-term studies are required. PMID- 26137800 TI - 3D and 2D left ventricular systolic function imaging-- from ejection fraction to deformation. Cardiac resynchronization therapy--substudy. AB - INTRODUCTION: 3D echocardiography offers options of left ventricular systolic function analysis. The aims of this study are: to assess the usefulness of 3D echocardiography, to test 3D regional measurements (with area strain) among a spectrum of patients and then to check prospectively the value of 3D echocardiography vs 2D in the assessment of response to resynchronization. METHODS: The first retrospective study group comprises 42 subjects: 23 consecutive patients with left ventricular systolic heart failure and 19 healthy control subjects. The left ventricle was assessed by: 2D-Simpson's biplane, 3D triplane and -automated volumetric method. Next, 24 patients undergoing cardiac resynchronization therapy were prospectively assessed before and after 6 months. A haemodynamic response criterion of 15% left ventricular end-systolic volume (ESV) reduction was used. RESULTS: The 3D volumetric method was the fastest method for left ventricular ejection fraction assessment (bi-33 vs tri-53 vs145 sec, ANOVA P < 0.001). In heart failure the only strain parameter associated with QRS width was global peak longitudinal strain (r = 0.47, P = 0.023). A high agreement in left ventricular ejection fraction and volumes between methods was observed. The following measures select resynchronization candidates in the heart failure group: (1) 3D global longitudinal strain (AUC-0.756; P = 0.022; the cut off value > -9.52%; 78% sensitivity, 80% specificity), radial strain (AUC-0.739; P = 0.086; cut-off value 20%; 78% sensitivity, 80% specificity) and area strain (AUC-0.733; P = 0.045; cut-off value > -13.5%; 67% sensitivity, 80% specificity). The agreement between the response assessment by Simpson's biplane and 3D was 78% with a negative predictive value of 100%. The lack of global area strain improvement after cardiac resynchronization therapy has a negative predictive value of 100% in the selection of non-responders. CONCLUSIONS: 3D echocardiography is applicable in the assessment of both preserved and reduced left ventricular ejection fraction. This assessment is fast and requires minimal user intervention. 3D strain may help in cardiac resynchronization therapy candidates and response assessment. After cardiac resynchronization, none of the patients were incorrectly identified as responder to cardiac resynchronization therapy by 3D algorithms compared to 2D Simpson's reference. PMID- 26137801 TI - Circulating adiponectin: a cardiometabolic marker associated with global cardiovascular risk. AB - OBJECTIVE: This study was designed to evaluate the relationship among circulating adiponectin (ADPN), left ventricular mass (LVM) and cardio-metabolic comorbidities in subjects at higher global cardiovascular risk (score of"Cuore Project"). METHODS: 115 consecutive subjects were grouped according to normal or low ADPN levels. Left ventricular internal diameter (LVID/h), total LV mass (LVM), LVM index (LVMI), relative wall thickness (RWT), LV ejection fraction by echocardiography and diastolic parameters, by pulsed-wave Doppler were calculated. RESULTS: Low-ADPN subjects were characterized by a significantly higher prevalence of some cardiometabolic comorbidities (obesity, visceral obesity, diabetes and insulin resistance, LVH, metabolic syndrome (MetS), coronary artery syndrome (CAD). BMI (P < 0.0001), WHR (P < 0.03), trigly cerides (P < 0.001), HOMA-IR (P < 0.001), LVM, LVMI, IVST and RWT (P < 0.0001) were significantly higher and HDL-C (P < 0.001) and LVEF were significantly lower in low-ADPN than in normal-ADPN subjects. LVMI correlated directly with BMI (P < 0.001), WHR (P < 0.001) MBP (P < 0.001), MetS (P < 0.001) and inversely with ADPN (P < 0.0001). Multiple regres- sion analysis indicated that ADPN was independently associated with LVMI. CONCLUSIONS: ADPN might be considered a key component mediating the cross-talk between adipose tissue, cardiac cells and the vasculature. Accordingly, its routine measurement might become a new target in the management of global CV risk. PMID- 26137802 TI - Impact of lifestyle modification on left ventricular function and cardiopulmonary exercise capacity in patients with heart failure with normal ejection fraction and cardiometabolic syndrome: a prospective interventional study. AB - BACKGROUND: Heart failure with normal left ventricular ejection fraction (HFNEF) accounts for about one third of all heart failure patients with considerable mortality. The metabolic syndrome (MS) is a risk factor for diastolic dysfunction and HFNEF. We hypothesized that modifying metabolic burden by exercise training and weight loss might improve left ventricular diastolic function, heart failure symptoms and rehospitalization rate. METHODS AND RESULTS: Forty patients with HFNEF, MS and prediabetes were enrolled in this prospective study. Echocardiography and cardiopulmonary exercise testing (CPET) were done at baseline and after 3 months lifestyle modification (LSM). NT-pro BNP and adiponectin were determined at baseline as both peptidehormones play a crucial role in MS and heart failure. After discharge a 3-month LSM program with the aim of weight reduction by diet and exercise was started. After the intervention period a weight reduction of >= 2% was defined as successful LSM (group A = 23 patients), while a weight reduction < 2% was classified as unsuccessful LSM (group B = 17 patients). At baseline NT-pro BNP (424 +/- 381 versus 121 +/- 99 pg/ml, P < 0.01) and adiponectin (10.1 +/- 6.2 versus 4.6-2.0 ug/ml, P < 0.01) were higher in group A than in group B. After 3 months of LSM, CPET showed a significant improve- ment of VO2 peak (P < 0.01), EqCO2 (P < 0.001), O2-pulse (P = 0.02) and VE / VCO2 slope (P = 0.01) in group A. After one year of follow-up a modest but significant reduction of left atrial size and mitral flow to mitral annulus velocity ratio E/E' was seen in group A. LSM resulted in significant improvement of NYHA status (P = 0.03) and higher freedom of rehospitalization (P = 0.04) in group A. CONCLUSION: Successful lifestyle modification in obese, prediabetic patients with HFNEF improves diastolic left ventricular function and cardiopulmonary exercise capacity. As these measures result in improved NYHA status and less hospitalization, LSM might be a promising approach to prevent chronic diastolic heart failure. PMID- 26137803 TI - Serum prolidase activity in patients with left ventricular diastolic dysfunction. AB - OBJECTIVES: Prolidase is an important factor in collagen metabolism, matrix remodelling and cell growth. Increased collagen turnover leading to increased ventricular stiffness plays an important role in the pathophysiology of left ventricular diastolic dysfunction (LVDD). This study aims to investigate whether serum prolidase activity is related to left ventricular diastolic function. METHODS: We studied 144 participants, and divided them into four groups according to the phase of diastolic dysfunction (66 with normal function, 46 with impaired relaxation, 19 with pseudonormalization, and 13 with restrictive-like filling). Assessment of diastolic filling was carried out with the measurements of E wave, A wave, E-wave deceleration time, isovolumic relaxation time, lateral tissue Doppler E S, E and A wave. Serum prolidase activity was measured by spectrophotometrical methods. RESULTS: Serum prolidase activity level was higher in patients with left ventricular diastolic dysfunction (LVDD) than without LVDD (P = 0.004). Also, prolidase activity values gradually increased from stage I through stage III in patients with LVDD. Multivariate analysis shows that LVDD is independently associated with age (beta = 0.066, SE = 0.017, P = 0.006), hypertension (beta = -1.252, SE = 0.354, P = 0.037) and prolidase activity (beta = 0.021, SE= 0.088, P= 0.045). CONCLUSION: Our data have shown that, in a selected group of patients, serum prolidase activity was positively and independently associated with the presence and severity of LVDD. PMID- 26137804 TI - The effect of physical exercise on arterial stiffness parameters in young sportsmen. AB - OBJECTIVE: This study aimed to determine the effect of single-bout exercise on aortic stiffness parameters in young basketball players. METHOD AND RESULTS: A total of 108 young male subjects (mean age 14.2 +/- 3.4 years) were enrolled into the study. Simultaneous measure- ment of aortic pulse wave velocity (PWVao) and augmentation index (Alxao) were performed with the oscillometric, occlusive device. Echocardiographic parameters of left ventricular systolic and diastolic function at rest were also measured in sportsmen. We did not find significant differences of resting PWVao in comparison with young sportsmen (S) and age matched healthy volunteers (V): 5.82 +/- 0.14 m/s vs 5.83 +/- 0.12 m/s for S and V groups, respectively. The values of PWVao measured after dynamic exercise, isometric exercise, and rest were 8.0 +/- 0.5 m/s, 5.86 +/- 0.1 m/s and 5.82 +/- 0.1 m/s, respectively. We confirmed that values after dynamic exercise are significantly different from those after isometric exercise (P < 0.01) and those after rest (P < 0.01). The Alxao values exhibited a considerable, but statistically non-significant, decrease during dynamic exercise in the three groups (11.7 +/- 7% vs 3.8 +/- 3% vs- 0.9 +/- 0.9% for groups 1, 2, and 3, respectively). CONCLUSION: We applied a feasible, clinically useful method which allowed us to measure changes in aortic PWV and Alx during acute, single-bout exercise on the basketball court in young sportsmen. PMID- 26137805 TI - Valsartan-induced cardioprotection involves angiotensin II type 2 receptor upregulation in isolated ischaemia and reperfused rat hearts. AB - The angiotensin II type 1 receptor (AT1R) antagonist protects the heart against acute ischaemia-reperfusion injury. The underlying mechanism is unclear. To determine the effects of angiotensin II type 1 receptor blockade, valsartan on AT1 and AT2 receptor during ischaemia reperfusion in isolated rat, the hearts of 24 SD rats were isolated, linked to Langendorff perfusion apparatus, and exposed to ischaemia for 30 min.The left ventricular systolic pressure, maximal uprising velocity of left ventricular pressure (+dp/dt(max)), maximal decreasing velocity of left ventricular pressure (-dp/dt(max)) and coronary flow were measured after stabilization of the perfusion.The isoenzyme of creatine kinase in the effluent liquid from the heart, AT1 and AT2 receptor mRNA and protein expression were measured after stabilization of the perfusion. The results showed that ischaemia reperfusion induced a marked decrease in left ventricular systolic pressure, +dp/dt(max) and -dp/dt(max) indicating severe cardiac dysfunction and decreased coronary effluence. Concurrently, myocardial AT1 and AT2 receptor mRNA and protein expression were increased with valsartan. However, AT2 receptor mRNA and protein expression decreased during ischaemia-reperfusion. The creatine kinase levels at different time points of the valsartan group were significantly lower. The results suggested that valsartan improved left ventricular function and increased coronary effluence because the angiotensin receptor blocker valsartan induced cardioprotection associated with upregulating AT2 receptor protein and mRNA expression after ischaemia-reperfusion in isolated rats. PMID- 26137806 TI - Summary 2014 ESC guidelines. PMID- 26137807 TI - A case of "broken heart" after endocarditis. PMID- 26137808 TI - Tension pneumopericardium after blunt chest trauma. PMID- 26137809 TI - Right-sided implantation of a biventricular ICD in a patient with persistent left superior vena cava: a challenging engagement. PMID- 26137810 TI - Large right ventricular mass causing outflow tract obstruction secondary to metastatic renal cell carcinoma. AB - We present a case of a 87-year-old patient presenting with signs suggestive of new-onset heart failure which lead to the diagnosis of a large right ventricular mass occupying the entire cavity and extending to the right ventricular outflow tract. PMID- 26137811 TI - Non-compaction associated with an ACTC1 mutation. PMID- 26137812 TI - [Mechanisms of viral emergence and interspecies transmission: the exemple of simian foamy viruses in Central Africa]. AB - A large proportion of viral pathogens that have emerged during the last decades in humans are considered to have originated from various animal species. This is well exemplified by several recent epidemics such as those of Nipah, Severe Acute Respiratory Syndrome, Avian flu, Ebola, Monkeypox, and Hantaviruses. After the initial interspecies transmission per se, the viruses can disseminate into the human population through various and distinct mechanisms. Some of them are well characterized and understood, thus allowing a certain level of risk control and prevention. Surprisingly and in contrast, the initial steps that lead to the emergence of several viruses, and of their associated diseases, remain still poorly understood. Epidemiological field studies conducted in certain specific high-risk populations are thus necessary to obtain new insights into the early events of this emergence process. Human infections by simian viruses represent increasing public health concerns. Indeed, by virtue of their genetic andphysiological similarities, non-human primates (NHPs) are considered to be likely the sources of viruses that can infect humans and thus may pose a significant threat to human population. This is well illustrated by retroviruses, which have the ability to cross species, adapt to a new host and sometimes spread within these new species. Sequence comparison and phylogenetic studies have thus clearly showed that the emergence of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in humans have resulted from several independent interspecies transmissions of different SIV types from Chimpanzees and African monkeys (including sooty mangabeys), respectively, probably during the first part of the last century. The situation for Human T cell Lymphotropic virus type 1 (HTLV-1) is, for certain aspects, quite comparable. Indeed, the origin of most HTLV-1 subtypes appears to be linked to interspecies transmission between STLV-1 infected monkeys and humans, followed by variable periods of evolution in the human host. In this review, after an introduction on emerging viruses, we will briefly present the results of a large epidemiological study performed in groups of Bantus and Pygmies living in villages and settlements located in the rain forest of the South region of Cameroon. These populations are living nearby the habitats of several monkeys and apes, often naturally infected by different retroviruses including SIV, STLV and simianfoamy virus. Most of the persons included in this study were hunters of such NHPs, thus at high risk of contact with infected body fluids (blood, saliva,...) during hunting activities. After reviewing the current available data on the discovery, cross-species transmission from monkeys and apes to humans of the simian foamy retroviruses, we will report the results of our study. Such infection is a unique natural model to study the different mechanisms of restriction of retroviral emergence in Humans. PMID- 26137813 TI - [Resequencing microarrays: a rapid tool for better identification and understanding of viral and bacterial emergence]. AB - The introduction of microarray technologies in microbiology has transformed the detection and characterization of microbial pathogens. Microarray-based platforms can be classified into different families according to their characteristics and applications. Resequencing microarrays have several advantages over other technologies for pathogen detection and characterization. PMID- 26137814 TI - [The brain-gut axis: insights from the obese pig model]. AB - The pig, which shares several similarities with humans, is increasingly used for biomedical research, particularly in nutrition and neurosciences. Recent studies in minipigs have shown that a deleterious nutritional environment (e.g. a high fat and high-sugar diet) induces obesity which, as in humans, is associated with increased adiposity, insulin resistance, modified eating behaviour, and altered gastric function and intestinal sensitivity. These changes are accompanied by differences in the activation matrices and metabolic activity of several brain areas. Using this animal model, we have revisited the concept of dual hedonic and homeostatic control of food intake. We have thus developed a minimally invasive and potentially reversible surgical approach to the control of food intake, as an alternative to bariatric surgery, based on chronic vagal stimulation at the abdominal level. PMID- 26137815 TI - [Effects of perinatal nutrition on developmental outcomes]. AB - The multifactorial nature of perinatal growth is now well established. The perinatal environment modulates each infant's genetic potential. Antenatal nutrition is dependent on maternal nutrition and is also subject to environmental factors such as tobacco smoke, which can significantly impact infant development. Current neonatal nutritional guidelines, aimed primarily at ensuring good nutrient tolerance, may no longer be optimal. Indeed, they can lead to malnutrition and growth retardation, and attempts to "catch up" through increased protein and calorie intake may have unwanted effects. Current data point to critical time windows during which nutritional optimization might improve infant development. New approches could help to prevent adult diseases of developmental origin. PMID- 26137816 TI - [Specificities of war surgery, and capacities of the military health service]. AB - In view of the recent evolution of military conflicts, particularly in the Afghan theater, and the conditions in which wounded warriors are managed in the field prior to hospitalization, the authors examine the technical specificities of medical teams, based on studies of avoidable mortality. War surgery has become a separate specialty, following the disappearance in France of the general surgical specialty, of which it was the military coun-terpart. The authors stress the role of hemorrhaging and its treatment, based on three strategies: damage control resuscitation, blood transfusion, and early evacuation within the "golden hour ". The French Armed Forces Health Service, in a new strategic plan, is refocusing its activity on war traumatology, through better education and training of medical-surgical teams and by opening up its scholarship structures to the French civilian public health service sector. PMID- 26137817 TI - [Current organization of disaster medicine]. AB - The concept of disaster medicine, derivedfrom medical management of casualties caused by terrorist attacks or earthquakes, began to be taught in medical school in 1982. It adapts military intervention tactics to civilian practices, and differentiates major disasters (in which preformed teams are sent to the scene) from disasters with limited effects (predefined plans form the backbone of the rescue organization). Management of blast and crush syndromes, triage, care of numerous burn victims, on-site amputation, necrotomy, medicopsychological support, mass decontamination, and rescue management are some of the aspects with which physicians should be familiar. Predefined intervention teams and ad hoc materials have been created to provide autonomous logistic support. Regulations, ethical aspects and managerial methods still need to be refined, and research and teaching must be given a new impetus. PMID- 26137818 TI - [The 50th anniversary of the first liver transplantation: from myth to reality. Tributes to Thomas Starzl, 2012 Lasker Prize]. AB - Chemical immunosuppression and the reversal of rejection permit to develop kidney transplantation and were incitative to start liver transplantation in 1963. However, the difficulties were many: wrong operative indications, inadequate immunosuppression, difficulty of etiologic diagnosis of jaundice, poor preservation of the graft. Cyclosporine was the key-step of the success. PMID- 26137819 TI - What Makes for a Good or Bad Death? PMID- 26137820 TI - What I Know for Sure About the 40 Years of ONS. PMID- 26137821 TI - Palliative Care Provides Support Throughout Treatment. Not Just at End of Life. PMID- 26137822 TI - How Can Palliative Care Discussions Occur Earlier in Patients' Diagnoses? PMID- 26137823 TI - Breaking Down Barriers in Advance Care Planning. PMID- 26137825 TI - When "Do Everything" Becomes "Do No More". PMID- 26137824 TI - How Do You Prepare to Discuss Advance Care Planning? PMID- 26137826 TI - What Is the Role of Pharmacy in Palliative and End-of-Life Care? PMID- 26137827 TI - The Case of the Confrontational Caregiver. PMID- 26137828 TI - How Death With Dignity Programs May Be Able to Fulfill Some Patients' Wishes. PMID- 26137829 TI - Get the Basics on End-of-Life Medications. PMID- 26137830 TI - Expanded Access Allows for Compassionate Use of Investigational Cancer Drugs. PMID- 26137831 TI - What Do Oncology Nurses Need to Know About Blood Transfusions for Anemia? PMID- 26137832 TI - Sometimes, the Latest or Most Aggressive Treatment Isn't Appropriate for Your Patient. PMID- 26137833 TI - Vegetarian Diets May Decrease Risk of Colorectal Cancer. PMID- 26137834 TI - Severe Heat Illness. What's the key to recognizing a patient in danger? PMID- 26137835 TI - Conducting the Student Interview. It's your best early chance to spot candidates not suited for EMS. AB - Student interviews help ensure a match between classroom imperatives and candidates'capabilities. Exploring students'maturity and judgment is often more important than confirming their academic proficiency. Walking into an interview unprepared can be as damaging for interviewers as for interviewees. Selecting the right people and the right process for conducting interviews depends on planning and practice. A team approach to interviewing can be particularly effective if team members take the time to discuss topics and roles before meeting with candidates. Although imprecise, interviews increase the chances that instructors and students will achieve mutually satisfying results, particularly when students play active roles. Next time we'll cover patient interviews. PMID- 26137836 TI - Best Practices in CE. How technology is changing the way we deliver continuing education. PMID- 26137837 TI - Why Research Is Important in EMS. We need an evidence base, and you can help develop it. PMID- 26137838 TI - Should Response Time be a Performance Indicator? A survey ot PinnacIe thought leaders' opinions. PMID- 26137839 TI - MIH Summit 2015 Report. Lessons learned from a fire-based MIH-CP Program. PMID- 26137840 TI - Using Prehospital Ultrasound for Cardiac Resuscitation. PMID- 26137841 TI - Transesophageal Echocardiography. PMID- 26137842 TI - Head of the Class. What makes a good EMS instructor?. PMID- 26137843 TI - A youth-led social marketing intervention to encourage healthy lifestyles, the EYTO (European Youth Tackling Obesity) project: a cluster randomised controlled0 trial in Catalonia, Spain. AB - BACKGROUND: The encouragement of healthy lifestyles for obesity prevention in young people is a public health priority. The European Youth Tackling Obesity (EYTO) project is a multicentric intervention project with participation from the United Kingdom, Portugal, the Czech Republic and Spain. The general aim of the EYTO project is to improve lifestyles, including nutritional habits and physical activity practice, and to prevent obesity in socioeconomically disadvantaged and vulnerable adolescents. The EYTO project works through a peer-led social marketing intervention that is designed and implemented by the adolescents of each participating country. Each country involved in the project acts independently. This paper describes the "Som la Pera" intervention Spanish study that is part of the EYTO project. METHODS/DESIGN: In Spain, the research team performed a cluster randomised controlled intervention over 2 academic years (2013-2015) in which 2 high-schools were designated as the control group and 2 high-schools were designated as the intervention group, with a minimum of 121 schoolchildren per group. From the intervention group, 5 adolescents with leadership characteristics, called "Adolescent Challenge Creators" (ACCs), were recruited. These 5 ACCs received an initial 4 h training session about social marketing principles and healthy lifestyle theory, followed by 24 sessions (1.30 h/session) divided in two academic years to design and implement activities presented as challenges to encourage healthy lifestyles among their peers, the approximately 180-200 high-school students in the intervention group. During the design of the intervention, it was essential that the ACCs used the 8 social marketing criteria (customer orientation, behaviour, theory, insight, exchange, competition, segmentation and methods mix). The expected primary outcomes from the Spanish intervention will be as follows: increases in the consumption of fruits and vegetables and physical activity practice along with reductions in TV/computer/game console use. The secondary outcomes will be as follows: increased breakfast consumption, engagement with local recreation and reduced obesity prevalence. The outcomes will be measured by the Health Behaviour in School-aged Children Study (HBSC) survey at baseline and at the end of the intervention. In the control group, no intervention was implemented, but the outcome measurements were collected in parallel with the intervention group. DISCUSSION: This study described a new methodology to improve lifestyles and to address adolescent obesity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02157402. Registered 03 June 2014. PMID- 26137845 TI - The causality between smoking and lung cancer among groups and individuals: addressing issues in tobacco litigation in South Korea. AB - This article discusses issues on the causality between smoking and lung cancer, which have been raised during the tobacco litigation in South Korea. It should be recognized that the explanatory ability of risk factor(s) for inter-individual variations in disease occurrence is different from the causal contribution of the risk factor(s) to disease occurrence. The affected subjects of the tobacco litigation in South Korea are lung cancer patients with a history of cigarette smoking. Thus, the attributable fraction of the exposed rather than the population attributable fraction should be used in the tobacco litigation regarding the causal contribution of smoking to lung cancer. Scientific evidence for the causal relationship between smoking and lung cancer is based on studies of individuals and groups, studies in animals and humans, studies that are observational or experimental, studies in laboratories and communities, and studies in both underdeveloped and developed countries. The scientific evidence collected is applicable to both groups and individuals. The probability of causation, which is calculated based on the attributable fraction for the association between smoking and lung cancer, could be utilized as evidence to prove causality in individuals. PMID- 26137844 TI - Improving treatment adherence for blood pressure lowering via mobile phone SMS messages in South Africa: a qualitative evaluation of the SMS-text Adherence SuppoRt (StAR) trial. AB - BACKGROUND: Effective use of proven treatments for high blood pressure, a preventable health risk, is challenging for many patients. Prompts via mobile phone SMS-text messaging may improve adherence to clinic visits and treatment, though more research is needed on impact and patient perceptions of such support interventions, especially in low-resource settings. METHOD: An individually randomised controlled trial in a primary care clinic in Cape Town (2012-14), tested the effect of an adherence support intervention delivered via SMS-texts, on blood pressure control and adherence to medication, for hypertensive patients. ( TRIAL REGISTRATION: ClinicalTrials.gov NCT02019823). We report on a qualitative evaluation that explored the trial participants' experiences and responses to the SMS-text messages, and identified barriers and facilitators to delivering adherence support via patients' own mobile phones. Two focus groups and fifteen individual interviews were conducted. We used comparative and thematic analysis approaches to identify themes and triangulated our analysis amongst three researchers. RESULTS: Most participants were comfortable with the technology of using SMS-text messages. Messages were experienced as acceptable, relevant and useful to a broad range of participants. The SMS-content, the respectful tone and the delivery (timing of reminders and frequency) and the relational aspect of trial participation (feeling cared for) were all highly valued. A subgroup who benefitted the most, were those who had been struggling with adherence due to high levels of personal stress. The intervention appeared to coincide with their readiness for change, and provided practical and emotional support for improving adherence behaviour. Change may have been facilitated through increased acknowledgement of their health status and attitudinal change towards greater self-responsibility. Complex interaction of psycho-social stressors and health service problems were reported as broader challenges to adherence behaviours. CONCLUSION: Adherence support for treatment of raised blood pressure, delivered via SMS-text message on the patient's own phone, was found to be acceptable, relevant and helpful, even for those who already had their own reminder systems in place. Our findings begin to identify for whom and what core elements of the SMS-text message intervention appear to work best in a low-resource operational setting, issues that future research should explore in greater depth. PMID- 26137846 TI - Joint Statement of the Ad-hoc Committee of the Korean Society for Preventive Medicine and the Korean Society of Epidemiology on Tobacco Lawsuits on the Causal Link Between Tobacco Smoking and Lung Cancer. PMID- 26137847 TI - TRES: Identification of Discriminatory and Informative SNPs from Population Genomic Data. AB - The advent of high-throughput genomic technologies is enabling analyses on thousands or even millions of single-nucleotide polymorphisms (SNPs). At the same time, the selection of a minimum number of SNPs with the maximum information content is becoming increasingly problematic. Available locus ranking programs have been accused of providing upwardly biased results (concerning the predicted accuracy of the chosen set of markers for population assignment), cannot handle high-dimensional datasets, and some of them are computationally intensive. The toolbox for ranking and evaluation of SNPs (TRES) is a collection of algorithms built in a user-friendly and computationally efficient software that can manipulate and analyze datasets even in the order of millions of genotypes in a matter of seconds. It offers a variety of established methods for evaluating and ranking SNPs on user defined groups of populations and produces a set of predefined number of top ranked loci. Moreover, dataset manipulation algorithms enable users to convert datasets in different file formats, split the initial datasets into train and test sets, and finally create datasets containing only selected SNPs occurring from the SNP selection analysis for later on evaluation in dedicated software such as GENECLASS. This application can aid biologists to select loci with maximum power for optimization of cost-effective panels with applications related to e.g. species identification, wildlife management, and forensic problems. TRES is available for all operating systems at http://mlkd.csd.auth.gr/bio/tres. PMID- 26137848 TI - Engineering evidence for carbon monoxide toxicity cases. AB - Unintentional carbon monoxide poisonings and fatalities lead to many toxicity cases. Given the unusual physical properties of carbon monoxide-in that the gas is odorless and invisible-unorganized and erroneous methods in obtaining engineering evidence as required during the discovery process often occurs. Such evidence gathering spans domains that include building construction, appliance installation, industrial hygiene, mechanical engineering, combustion and physics. In this paper, we attempt to place a systematic framework that is relevant to key aspects in engineering evidence gathering for unintentional carbon monoxide poisoning cases. Such a framework aims to increase awareness of this process and relevant issues to help guide legal counsel and expert witnesses. PMID- 26137850 TI - Evaluation of Efficacy of an Herbal Compound on Dry Mouth in Patients With Head and Neck Cancers: A Randomized Clinical Trial. AB - Dry mouth is a common complication of radiotherapy for head and neck cancers. This study compared the efficacy of an herbal compound containing Malva sylvestris and Alcea digitata (Boiss) with artificial saliva (Hypozalix) for improving the symptoms of dry mouth in head and neck cancer patients. The study examined a total of 62 subjects assigned to 2 groups. The herbal compound and Hypozalix were administered for 4 weeks. Efficacy was assessed using the visual analog scale and by grading the degree of dry mouth. Both groups showed a significant difference between visual analog scale before and following intervention. There was also a significant difference in visual analog scale between groups at 4 weeks after onset of intervention. The herbal group showed a significant difference between the grade of dry mouth before and after intervention, but no change was observed for grade of dry mouth in the Hypozalix group. This study supports the efficacy of the herbal compound for controlling symptoms of dry mouth in head and neck cancer patients. PMID- 26137849 TI - Divergent target recognition by coexpressed 5'-isomiRs of miR-142-3p and selective viral mimicry. AB - Sequence heterogeneity at the ends of mature microRNAs (miRNAs) is well documented, but its effects on miRNA function are largely unexplored. Here we studied the impact of miRNA 5'-heterogeneity, which affects the seed region critical for target recognition. Using the example of miR-142-3p, an emerging regulator of the hematopoietic lineage in vertebrates, we show that naturally coexpressed 5'-variants (5'-isomiRs) can recognize largely distinct sets of binding sites. Despite this, both miR-142-3p isomiRs regulate exclusive and shared targets involved in actin dynamics. Thus, 5'-heterogeneity can substantially broaden and enhance regulation of one pathway. Other 5'-isomiRs, in contrast, recognize largely overlapping sets of binding sites. This is exemplified by two herpesviral 5'-isomiRs that selectively mimic one of the miR 142-3p 5'-isomiRs. We hypothesize that other cellular and viral 5'-isomiRs can similarly be grouped into those with divergent or convergent target repertoires, based on 5'-sequence features. Taken together, our results provide a detailed characterization of target recognition by miR-142-3p and its 5'-isomiR-specific viral mimic. We furthermore demonstrate that miRNA 5'-end variation leads to differential targeting and can thus broaden the target range of miRNAs. PMID- 26137851 TI - Riboswitch-mediated Attenuation of Transgene Cytotoxicity Increases Adeno associated Virus Vector Yields in HEK-293 Cells. AB - Cytotoxicity of transgenes carried by adeno-associated virus (AAV) vectors might be desired, for instance, in oncolytic virotherapy or occur unexpectedly in exploratory research when studying sparsely characterized genes. To date, most AAV-based studies use constitutively active promoters (e.g., the CMV promoter) to drive transgene expression, which often hampers efficient AAV production due to cytotoxic, antiproliferative, or unknown transgene effects interfering with producer cell performance. Therefore, we explored artificial riboswitches as novel tools to control transgene expression during AAV production in mammalian cells. Our results demonstrate that the guanine-responsive GuaM8HDV aptazyme efficiently attenuates transgene expression and associated detrimental effects, thereby boosting AAV vector yields up to 23-fold after a single addition of guanine. Importantly, riboswitch-harboring vectors preserved their ability to express functional transgene at high levels in the absence of ligand, as demonstrated in a mouse model of AAV-TGFbeta1-induced pulmonary fibrosis. Thus, our study provides the first application-ready biotechnological system-based on aptazymes, which should enable high viral vector yields largely independent of the transgene used. Moreover, the RNA-intrinsic, small-molecule regulatable mode of action of riboswitches provides key advantages over conventional transcription factor-based regulatory systems. Therefore, such riboswitch vectors might be ultimately applied to temporally control therapeutic transgene expression in vivo. PMID- 26137852 TI - Optogenetic Vision Restoration Using Rhodopsin for Enhanced Sensitivity. AB - Retinal disease is one of the most active areas of gene therapy, with clinical trials ongoing in the United States for five diseases. There are currently no treatments for patients with late-stage disease in which photoreceptors have been lost. Optogenetic gene therapies are in development, but, to date, have suffered from the low light sensitivity of microbial opsins, such as channelrhodopsin and halorhodopsin, and azobenzene-based photoswitches. Several groups have shown that photoreceptive G-protein-coupled receptors (GPCRs) can be expressed heterologously, and photoactivate endogenous Gi/o signaling. We hypothesized such a GPCR could increase sensitivity due to endogenous signal amplification. We targeted vertebrate rhodopsin to retinal ON-bipolar cells of blind rd1 mice and observed restoration of: (i) light responses in retinal explants, (ii) visually evoked potentials in visual cortex in vivo, and (iii) two forms of visually guided behavior: innate light avoidance and discrimination of temporal light patterns in the context of fear conditioning. Importantly, both the light responses of the retinal explants and the visually-guided behavior occurred reliably at light levels that were two to three orders of magnitude dimmer than required for channelrhodopsin. Thus, gene therapy with native light-gated GPCRs presents a novel approach to impart light sensitivity for visual restoration in a useful range of illumination. PMID- 26137853 TI - Benefits of Neuronal Preferential Systemic Gene Therapy for Neurotransmitter Deficiency. AB - Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disease that impairs synthesis of dopamine and serotonin. Children with AADC deficiency exhibit severe motor, behavioral, and autonomic dysfunctions. We previously generated an IVS6+4A>T knock-in mouse model of AADC deficiency (Ddc(KI) mice) and showed that gene therapy at the neonatal stage can rescue this phenotype. In the present study, we extended this treatment to systemic therapy on young mice. After intraperitoneal injection of AADC viral vectors into 7-day old Ddc(KI) mice, the treated mice exhibited improvements in weight gain, survival, motor function, autonomic function, and behavior. The yfAAV9/3-Syn-I mAADC-treated mice showed greater neuronal transduction and higher brain dopamine levels than AAV9-CMV-hAADC-treated mice, whereas AAV9-CMV-hAADC-treated mice exhibited hyperactivity. Therefore, neurotransmitter-deficient animals can be rescued at a young age using systemic gene therapy, although a vector for preferential neuronal expression may be necessary to avoid hyperactivity caused by this treatment. PMID- 26137854 TI - Highly responsive MoS2 photodetectors enhanced by graphene quantum dots. AB - Molybdenum disulphide (MoS2), which is a typical semiconductor from the family of layered transition metal dichalcogenides (TMDs), is an attractive material for optoelectronic and photodetection applications because of its tunable bandgap and high quantum luminescence efficiency. Although a high photoresponsivity of 880 2000 AW(-1) and photogain up to 5000 have been demonstrated in MoS2-based photodetectors, the light absorption and gain mechanisms are two fundamental issues preventing these materials from further improvement. In addition, it is still debated whether monolayer or multilayer MoS2 could deliver better performance. Here, we demonstrate a photoresponsivity of approximately 10(4) AW( 1) and a photogain of approximately 10(7) electrons per photon in an n-n heterostructure photodetector that consists of a multilayer MoS2 thin film covered with a thin layer of graphene quantum dots (GQDs). The enhanced light matter interaction results from effective charge transfer and the re-absorption of photons, leading to enhanced light absorption and the creation of electron hole pairs. It is feasible to scale up the device and obtain a fast response, thus making it one step closer to practical applications. PMID- 26137856 TI - Layered titanium diboride: towards exfoliation and electrochemical applications. AB - Layered transition metal diborides (TMDB), amongst other refractory metal borides, are commonly employed for material fabrication such as wear- and corrosion-resistant coatings due to their impressive chemical stability and thermal conductivity. In spite of the wide scope of studies carried out on TMDB in the physical field, investigations on its electrochemistry remain limited. Since the physical properties play a vital role in any material's electrochemical behaviour, we explore the viability of the most popular form of titanium boride, layered TiB2, as catalysts for electrochemical energy reactions, including hydrogen evolution and oxygen reduction. Three types of TiB2 were compared in this work - TiB2 separately modified with sodium naphtalenide and butyllithium in an attempt to exfoliate TiB2 and unmodified TiB2. The electrocatalytic activity displayed by all three TiB2 materials provides a wider range of opportunities for the application of TiB2 in material studies. PMID- 26137855 TI - Different chronological patterns of appearance of blood derived milk components during mastitis indicate different mechanisms of transfer from blood into milk. AB - This study aimed to describe chronological patterns of changes of various candidate blood components in milk during the acute phase of a mammary immune response in detail. Eight dairy cows were challenged with Escherichia coli lipopolysaccharide in one udder quarter. Milk from challenged and control quarters and blood samples were taken before, and 1 and 2 h after challenge and then every 15 min until 5 h after challenge. The SCC, serum albumin, immunoglobulin (Ig)G1, IgG2, lactate dehydrogenase (LDH), and L-lactate in milk and blood, and alpha-lactalbumin in blood were analysed. All selected parameters in milk increased in challenged quarters but did not increase in control quarters. Milk IgG1, IgG2, serum albumin, and LDH were already significantly increased at 2 h after challenge whereas a significant increase of SCC was detectable at 2.75 h and L-lactate was increased at 2.25 h after challenge. In blood L-lactate was increased at 3.75 h after challenge, however, other factors in blood did not change significantly within the 5 h of experiment. In conclusion, the increase of blood components in milk during inflammation follows two different patterns: There is a rapid increase for IgG1, IgG2, or LDH, before the increase of SCC, and their concentrations reach a plateau within 3 h. On the other hand, SCC and L-lactate show a slower but consistent increase not reaching a plateau within 5 h after LPS challenge. L-lactate increases to higher concentrations in milk than in blood. This clearly shows that the increase of blood components follows different patterns and is therefore a controlled and compound-specific process and not exclusively an unspecific type of leakage. PMID- 26137857 TI - Brief report: enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. AB - OBJECTIVE: Innate lymphoid cells (ILCs) are a recently discovered group of cells that are essential to epithelial homeostasis and are implicated in psoriasis pathogenesis, yet they have never been reported in psoriatic arthritis (PsA). METHODS: ILC classes and subsets were characterized in the peripheral blood (PB) of healthy controls, patients with psoriasis, and patients with PsA and in the synovial fluid (SF) of patients with PsA and patients with rheumatoid arthritis (RA). Cell surface marker expression and intracellular cytokine production following stimulation were analyzed using flow cytometry. RESULTS: ILCs were identified in the SF and were 4-fold more abundant in PsA SF than in PsA PB. Fewer CCR6+ ILCs were found in PsA PB than in healthy control PB, while PsA SF was enriched for CCR6+ ILCs compared to PsA PB and RA SF. Natural cytotoxicity receptor NKp44+ group 3 ILCs were rare in PB and RA SF, but abundant in PsA SF. Increased numbers of interleukin-17A (IL-17A)-producing ILCs were present in PsA SF compared to RA SF. CCR6, NKp44, and melanoma cell adhesion molecule (MCAM) were expressed on the cell surface of SF ILCs that produced IL-17A. The number of circulating NKp44+, CCR6+, and MCAM+ ILCs in blood was inversely correlated with PsA disease activity. CONCLUSION: Our findings indicate that PsA SF is enriched for group 3 ILCs that express CCR6 and NKp44, which distinguishes the synovial compartment from RA. The increased IL-17A production by SF ILCs indicates a novel role for ILCs in PsA. PMID- 26137858 TI - Comparative epigenomics: a powerful tool to understand the evolution of DNA methylation. AB - Understanding how developmental and functional complexity of organisms evolves is a longstanding challenge in biology. Genetic mutation has long been thought to be the cause of biological complexity. However, increasing evidence indicates that epigenetic variation provides a parallel path for the evolution of biological complexity. Cytosine DNA methylation, the addition of a chemical mark on DNA, is a conserved and essential gene regulatory mechanism. Recent studies have greatly advanced our understanding of the DNA methylation landscapes and key regulatory components across many species. In this review, I summarize recent advances in understanding DNA methylation from an evolutionary perspective. Using comparative approaches, I highlight the conservation and divergence of DNA methylation patterns and regulatory machinery in plants and other eukaryotic organisms. PMID- 26137859 TI - Design of a hyperpolarized (15)N NMR probe that induces a large chemical-shift change upon binding of calcium ions. AB - Ca(2+) is a fundamental metal ion for physiological functioning. Therefore, molecular probes for Ca(2+) analysis are required. Recently, a hyperpolarized NMR probe has emerged as a promising tool. Here, we report a new design of a hyperpolarized NMR probe for Ca(2+), which showed a large chemical shift change upon binding to Ca(2+) and was applied for Ca(2+) sensing in a hyperpolarized state. PMID- 26137860 TI - Hrd1 and ER-Associated Protein Degradation, ERAD, are Critical Elements of the Adaptive ER Stress Response in Cardiac Myocytes. AB - RATIONALE: Hydroxymethyl glutaryl-coenzyme A reductase degradation protein 1 (Hrd1) is an endoplasmic reticulum (ER)-transmembrane E3 ubiquitin ligase that has been studied in yeast, where it contributes to ER protein quality control by ER-associated degradation (ERAD) of misfolded proteins that accumulate during ER stress. Neither Hrd1 nor ERAD has been studied in the heart, or in cardiac myocytes, where protein quality control is critical for proper heart function. OBJECTIVE: The objective of this study were to elucidate roles for Hrd1 in ER stress, ERAD, and viability in cultured cardiac myocytes and in the mouse heart, in vivo. METHODS AND RESULTS: The effects of small interfering RNA-mediated Hrd1 knockdown were examined in cultured neonatal rat ventricular myocytes. The effects of adeno-associated virus-mediated Hrd1 knockdown and overexpression were examined in the hearts of mice subjected to pressure overload-induced pathological cardiac hypertrophy, which challenges protein-folding capacity. In cardiac myocytes, the ER stressors, thapsigargin and tunicamycin increased ERAD, as well as adaptive ER stress proteins, and minimally affected cell death. However, when Hrd1 was knocked down, thapsigargin and tunicamycin dramatically decreased ERAD, while increasing maladaptive ER stress proteins and cell death. In vivo, Hrd1 knockdown exacerbated cardiac dysfunction and increased apoptosis and cardiac hypertrophy, whereas Hrd1 overexpression preserved cardiac function and decreased apoptosis and attenuated cardiac hypertrophy in the hearts of mice subjected to pressure overload. CONCLUSIONS: Hrd1 and ERAD are essential components of the adaptive ER stress response in cardiac myocytes. Hrd1 contributes to preserving heart structure and function in a mouse model of pathological cardiac hypertrophy. PMID- 26137861 TI - Angiotensin II Induces Skeletal Muscle Atrophy by Activating TFEB-Mediated MuRF1 Expression. AB - RATIONALE: Skeletal muscle wasting with accompanying cachexia is a life threatening complication in congestive heart failure. The molecular mechanisms are imperfectly understood, although an activated renin-angiotensin aldosterone system has been implicated. Angiotensin (Ang) II induces skeletal muscle atrophy in part by increased muscle-enriched E3 ubiquitin ligase muscle RING-finger-1 (MuRF1) expression, which may involve protein kinase D1 (PKD1). OBJECTIVE: To elucidate the molecular mechanism of Ang II-induced skeletal muscle wasting. METHODS AND RESULTS: A cDNA expression screen identified the lysosomal hydrolase coordinating transcription factor EB (TFEB) as novel regulator of the human MuRF1 promoter. TFEB played a key role in regulating Ang II-induced skeletal muscle atrophy by transcriptional control of MuRF1 via conserved E-box elements. Inhibiting TFEB with small interfering RNA prevented Ang II-induced MuRF1 expression and atrophy. The histone deacetylase-5 (HDAC5), which was directly bound to and colocalized with TFEB, inhibited TFEB-induced MuRF1 expression. The inhibition of TFEB by HDAC5 was reversed by PKD1, which was associated with HDAC5 and mediated its nuclear export. Mice lacking PKD1 in skeletal myocytes were resistant to Ang II-induced muscle wasting. CONCLUSION: We propose that elevated Ang II serum concentrations, as occur in patients with congestive heart failure, could activate the PKD1/HDAC5/TFEB/MuRF1 pathway to induce skeletal muscle wasting. PMID- 26137863 TI - Adipose tissue-derived microvascular fragments: natural vascularization units for regenerative medicine. AB - The establishment of effective vascularization is a key challenge in regenerative medicine. To achieve this, the transplantation of native microvascular fragments has emerged as a promising novel concept. Microvascular fragments can be isolated in large amounts from fat tissue, exhibit a high angiogenic activity, and represent a rich source of mesenchymal stem cells. Originally, microvascular fragments have been used in angiogenesis research for the isolation of capillary endothelium and for functional sprouting assays. More recent studies have demonstrated that they rapidly develop into microvascular networks after transfer into tissue defects. Moreover, they are suitable for the generation of prevascularized tissue constructs. Hence, a wide range of future medical applications may benefit from the use of these natural vascularization units. PMID- 26137862 TI - [Drug interactions in pain therapy]. AB - BACKGROUND: Pain is one of the most common reasons for consulting a physician. Chronic pain patients often suffer from a variety of comorbidities, such as depression and anxiety and they are therefore often simultaneously treated with more than one drug. The probability of drug interactions increases with every additional drug. MATERIAL AND METHODS: A systematic internet and literature search up to February 2015 was carried out. Systematic lists were included. In addition, the drug prescription information sheets were used and an internet search via Pubmed and google.com was carried out for drugs alone and in combination in order to find substance-specific interactions. RESULTS: A differentiation is made between pharmaceutical, pharmacodynamic and pharmacokinetic drug interactions. Pharmaceutical interactions are caused by chemical, physical or physicochemical incompatibility of drugs or adjuvants used. These can even occur outside the body and during concomitant administration via the same route. A pharmacodynamic interaction in pain management is for example the additive sedative effect of opioids and benzodiazepines when taken together. Pharmacokinetic interactions occur during the absorption, distribution, metabolism and in the elimination phases. CONCLUSION: Many drug interactions can be avoided by careful and continuous evaluation of pharmacotherapy and if necessary its adaptation; however, a sound knowledge of the underlying pharmacological mechanisms and the properties of currently used analgesics is necessary. PMID- 26137864 TI - Organic semiconductor/gold interface interactions: from physisorption on planar surfaces to chemical reactions with metal nanoparticles. AB - The interaction of gold nanoparticles (AuNPs) with prototypical organic semiconductors used in optoelectronics, namely, tris(8-hydroxyquinoline)aluminium (Alq3 ) and 4,4-bis[N-(1-naphthyl)-N-phenylamino]diphenyl (alpha-NPD), is investigated in situ by X-ray photoelectron spectroscopy (XPS). These AuNPs-on molecule experiments are compared with the reversed molecule-on-Au cases. The molecules-on-Au systems show only weak interactions, and the evolution of the XP spectra is dominated by final-state effects. In contrast, in the AuNPs-on molecules cases, both initial-state effects and final-state effects occur. Spectral features arising for both molecules and metal indicate charge transfer and the formation of organometallic complexes (initial-state effects). The energy shift in the metal emission underlines the size-induced nanometric nature of the molecule/Au interaction (final-state effects). Consequently, the chemical interaction between metals and organic semiconductors likely depends strongly on the deposition sequence in general. PMID- 26137865 TI - Valve sparing: aortic root replacement with the reimplantation technique. AB - Aortic valve-sparing procedures are alternative options to aortic valve replacement in patients with aortic root aneurysm and/or severe aortic regurgitation reducing the risk of prosthesis-related complications, such as thromboembolism, and have no need for long-term oral anticoagulation. However, these techniques are technically demanding and long-term results are highly dependent on perfect intraoperative restoration of valve function. We describe a systematic approach to aortic valve-sparing aortic root replacement with the reimplantation technique the way it is currently performed in our institution. PMID- 26137866 TI - Adhering to the principles of surgical ablation. PMID- 26137867 TI - [Respiratory muscle strength test: is it realistic in young children?]. AB - OBJECTIVE: To determine the success rate of the manovacuometry test in children between 4 and 12 years of age. METHODS: Cross-sectional study involving children and adolescents from 4 to 12 years of age, enrolled in three basic education schools. All subjects had the anthropometric and respiratory muscle strength (maximum inspiratory pressure and maximum expiratory pressure) data measured. Students whose parents did not authorize participation or who did not want to undergo the test were excluded. The test was considered successful when the subject reached acceptability (no air leaks) and reproducibility (variation <10% between the two major maneuvers) criteria established by guidelines. Failure was defined when subjects did not meet the above criteria. Data were expressed as mean and standard deviation and in absolute and relative frequency. The comparison between proportions was performed using the chi-square test. RESULTS: We included 196 children and adolescents, mean age of 8.4+/-2.5 years, 53.1% female. The success rate of the manovacuometry test in children and adolescents evaluated was 92.3%. When comparing the differences between the success rates of preschool children with those children and adolescents of school age, there was a significantly lower success rate in the pre-school (85.1%) group compared to the school group (94.6%) (p=0.032). However, no significant differences (p=0.575) were found when gender comparisons were performed. CONCLUSIONS: The manovacuometry test showed a high success rate in both preschool and school population assessed. Furthermore, the rate of success appears to be related to aging. PMID- 26137868 TI - [Usefulness of the WHOQOL-BREF questionnaire in assessing the quality of life of parents of children with asthma]. AB - OBJECTIVE: To evaluate the quality of life (QOL) of parents of children with asthma and to analyze the internal consistency of the generic QOL tool World Health Organization Quality of Life, abbreviated version (WHOQOL-BREF). METHODS: We evaluated the QOL of parents of asthmatic and healthy children aged between 8 16, using the generic WHOQOL-BREF questionnaire. We also evaluated the internal consistency using Cronbach's alpha (alphaC), in order to determine whether the tool had good validity for the target audience. RESULTS: The study included 162 individuals with a mean age of 43.8+/-13.6 years, of which 104 were female (64.2%) and 128 were married (79.0%). When assessing the QOL, the group of parents of healthy children had higher scores than the group of parents of asthmatic children in the four areas evaluated by the questionnaire (Physical, Psychological Health, Social Relationships and Environment), indicating a better quality of life. Regarding the internal consistency of the WHOQOL-BREF, values of alphaC were 0.86 points for the group of parents of asthmatic children, and 0.88 for the group of parents of healthy children. CONCLUSIONS: Parents of children with asthma have impaired quality of life due to their children's disease. Furthermore, the WHOQOL-BREF, even as a generic tool, showed to be practical and efficient to evaluate the quality of life of parents of asthmatic children. PMID- 26137869 TI - Virtual reality suturing task as an objective test for robotic experience assessment. AB - BACKGROUND: We performed a pilot study using a single virtual-simulation suturing module as an objective measurement to determine functional use of the robotic system. This study will assist in designing a study for an objective, adjunctive test for use by a surgical proctor. METHODS: After IRB approval, subjects were recruited at a robotic renal surgery course to perform two attempts of the "Tubes" module without warm-up using the Da Vinci(r) Surgical Skills SimulatorTM. The overall MScore (%) from the simulator was compared among various skill levels to provide construct validity. Correlation with MScore and number of robotic cases was performed and pre-determined skill groups were tested. Nine metrics that make up the overall score were also tested via paired t test and subsequent logistic regression to determine which skills differed among experienced and novice robotic surgeons. RESULTS: We enrolled 38 subjects with experience ranging from 0- < 200 robotic cases. Median time to complete both tasks was less than 10 min. The MScore on the first attempt was correlated to the number of previous robotic cases (R(2) = 0.465; p = 0.003). MScore was different between novice and more experienced robotic surgeons on the first (44.7 vs. 63.9; p = 0.005) and second attempt (56.0 vs. 69.9; p = 0.037). CONCLUSION: A single virtual simulator exercise can provide objective information in determining proficient use of the robotic surgical system. PMID- 26137870 TI - Determinants of impact of a practice accreditation program in primary care: a qualitative study. AB - BACKGROUND: Practice accreditation is a widely used method to assess and improve the quality of healthcare services. In the Netherlands, a practice accreditation program was implemented in primary medical care. We aimed to identify determinants of impact of a practice accreditation program, building on the experiences of primary care professionals who had participated in this program. METHODS: An interview study was done to document the experiences of 33 participating primary care professionals and used to identify determinants of outcomes. The Consolidated Framework for Implementation Research (CFIR) was used as framework for the qualitative analysis. RESULTS: After analyzing 23 interviews saturation was reached. The practice accreditation program is based on structured quality improvement, but only some of its elements were identified as determinants of impact. Factors that were perceived to facilitate implementation of the program were: designating one person responsible for the program, ensuring clear lines of communication within the whole practice team and having affinity with or stimulate enthusiasm for improving quality of care. Contextual factors such as participation in a care group and being connected to the GP educational institute were important for actual change. The accreditation program was perceived to have positive effects on team climate and commitment to quality of care in the practice team. The perception was that patient care was not directly influenced by the accreditation program. Receiving a certificate for completing the accreditation program seemed to have little added value to participants. CONCLUSIONS: Practice accreditation may have positive outcomes on quality of care, but not all planned elements may contribute to its outcomes. Both factors in the accreditation process and in the context were perceived as determinants of quality improvement. The challenge is to build on facilitating factors, while reducing the elements of accreditation that do not contribute to its impact. PMID- 26137871 TI - Subgroup analysis of patients with G2 gastroenteropancreatic neuroendocrine tumors. AB - Neuroendocrine tumors (NET) are malignancies with an increasing incidence rate. NETs are graded or classified by the expression level of Ki67, a proliferation marker in Grade 1 and 2 tumors. Out of 120 patients who visited our hospital between 2003 and 2012, 40 were classified as G2 NET. This study was mainly designed to investigate a new threshold for optimising the Ki67 system. Patients were subdivided into two new groups according to Ki67 (group 1 = 3-9%, group 2 = 10-20%). Twenty-five patients were allocated to group 1 and 15 to group 2. The primary tumor originated in 46% from the foregut and 68% NET were functionally active. Patients were treated in 88 versus 60% by surgery, 48 versus 80% by somatostatin analogs, 0 versus 20% by chemotherapy, 2,5 versus 0% by Everolimus and 32 versus 47% underwent peptide receptor radionuclide therapy. Group 1 patients showed a significantly (p = 0.01) better survival compared with group 2 and also a significant difference of Chromogranin A (p = 0.03) and alkaline phosphatase (p = 0.01). In addition, all patients with elevated lactate dehydrogenase showed a significantly (p = 0.03) shorter survival. Prognostic relevance of G2 NETs may be improved by using a new boundary. Patients with Ki67 of 3-9% showed a better response to current treatment methods and significantly longer survival compared to group 2. Thus, our data clearly show that patients with higher G2 proliferation index should be treated differently. Finally, LDH has been found to be a new prognostic factor in patients with G2 NET. PMID- 26137872 TI - Management options of congenital pouch colon--a rare variant of anorectal malformation. AB - PURPOSE: Congenital pouch colon (CPC) was analysed for anatomical variations and surgical options. METHODS: Records of CPC patients managed between 1999 and 2014 were studied. CPC was classified as complete (CCPC) and incomplete (ICPC) pouch. RESULTS: Of 400 cases of high anorectal malformations, 68 cases were CPC (17%). Male:female ratio was 2:1. Fistulous communication was colovesical, colocloacal, colovaginal and absent in 42, 15, 8 and 3 cases. ICPC and CCPC was 48 (70%) and 20 (30%). In neonatal period, proximal/end colostomy (31), ileostomy (6), pouch excision with abdominoperineal pull-through (18 cases) and coloplasty with end colostomy (7) were done. 6 presented as infants including 3 referred cases of CCPC with a window colostomy. Definitive surgery was completed in 56. Severe colonic dilatation after coloplasty was noted in 5, requiring excision of coloplasty segment in 2. Histopathology of excised pouch (45) showed muscle layer disorganization, widened sub mucosa, prominent vasculature and mature and immature ganglion cells, with no hypertrophy of nerve fibres. Diarrhoea and faecal incontinence (soiling) were more frequent in patients with CCPC versus ICPC. Six neonates with CCPC died. Six are awaiting definitive surgery. CONCLUSION: CPC had 8.8% neonatal mortality. Pouch excision and definitive procedure are feasible in neonates with CPC. Coloplasty in CCPC may result in postoperative colonic dilatation. PMID- 26137874 TI - Comparing Humoral and Cellular Immune Response Against HBV Vaccine in Kidney Transplant Patients. AB - Host protection upon vaccination usually results from the complex interplay of humoral and cellular components of the immune system. Exploring hepatitis B surface antigen (HBsAg)-specific T cell responses and their correlation with humoral responses under immunosuppression, we analyzed 51 renal transplant recipients, differing in HBV vaccine-specific antibody titers (non [NRs]-, low [LRs]-, and high responders [HRs]) and in 22 healthy controls (HCs) in a cross sectional study. HBsAg-specific T cells were analyzed by flow cytometry according to expression of activation markers CD40L and/or CD69, and the cytokines IFNgamma, IL-2, TNFalpha, and IL-17. No significant differences in responder rate and magnitude of HBsAg-specific T cell responses were found between HCs and HRs. Interestingly, HBsAg-specific Th-cells were also observed in 50% of humoral NRs. Frequencies of HBsAg-specific CD40L+ Th-cells were significantly higher in HRs compared to LRs (p = 0.009) and in LRs in comparison to NRs (p = 0.043). All but NRs showed a predominance of multi-potent HBsAg-specific TNFalpha+IL-2+ Th-cells. As expected, HBsAg-specific CD8(+) T cells were rarely found. In conclusion, mounting of hepatitis B vaccine-specific T cell responses is possible in kidney transplant recipients despite immunosuppression. Detection of HBV-specific Th cells in a significant proportion of humoral NRs contributes to the current discussion on conferring immune protection by cellular memory in such patients. PMID- 26137873 TI - Knockout mouse models of Hirschsprung's disease. AB - PURPOSE: Hirschsprung's disease (HSCR) is a developmental disorder of the enteric nervous system, which occurs due to the failure of neural crest cell migration. Rodent animal models of aganglionosis have contributed greatly to our understanding of the genetic basis of HSCR. Several natural or target mutations in specific genes have been reported to produce developmental defects in neural crest migration, differentiation or survival. The aim of this study was to review the currently available knockout models of HSCR to better understand the molecular basis of HSCR. METHODS: A review of the literature using the keywords "Hirschsprung's disease", "aganglionosis", "megacolon" and "knockout mice model" was performed. Resulting publications were reviewed for relevant mouse models of human aganglionosis. Reference lists were screened for additional relevant studies. RESULTS: 16 gene knockout mouse models were identified as relevant rodent models of human HSCR. Due to the deletion of a specific gene, the phenotypes of these knockout models are diverse and range from small bowel dilatation and muscular hypertrophy to total intestinal aganglionosis. CONCLUSIONS: Mouse models of aganglionosis have been instrumental in the discovery of the causative genes of HSCR. Although important advances have been made in understanding the genetic basis of HSCR, animal models of aganglionosis in future should further help to identify the unknown susceptibility genes in HSCR. PMID- 26137875 TI - Protein-Coated Microcrystals from Candida rugosa Lipase: Its Immobilization, Characterization, and Application in Resolution of Racemic Ibuprofen. AB - In this study, an economical heterogeneous biocatalyst, protein-coated microcrystals (PCMCs), was prepared from a commercial Candida rugosa lipase (CRL) and used for catalyzing esterification of (R, S)-ibuprofen enantiomers with isooctanol in isooctane. The main variables controlling the process (precipitating solvents, pH, saturated K2SO4 solution, and water content) were optimized via single-factorial experiments. Under optimum conditions, the enantiomeric excess of active S(+)-ibuprofen and total conversion rate were 97.34 and 49.83 %, respectively, and the corresponding enzyme (PCMC-CRL) activity attained 387.29 MUmol/min/g protein, a 5.78-fold enhancement over the free lipase powder. Additionally, the thermostability, organic-solvent tolerance, and operational stability of PCMC-CRL were greatly improved as compared to the free enzyme. Fourier transform infrared (FTIR) spectroscopy was employed to reveal the correlation between conformation and enzyme activity enhancement. Moreover, the PCMC-CRL retained most of its original activity following use in more than 15 successive batches, suggesting that it exhibits adequate operational stability. These results indicate that PCMC-CRL is of great potential use in industrial applications. PMID- 26137876 TI - HPLC-ESI-MS(n) Analysis, Fed-Batch Cultivation Enhances Bioactive Compound Biosynthesis and Immune-Regulative Effect of Adventitious Roots in Pseudostellaria heterophylla. AB - A electrospray ionization tandem mass spectrometry (ESI-MS(n)) analysis was performed in order to identify the active composition in Pseudostellaria heterophylla adventitious roots. Pseudostellarin A, C, D, and G were identified from P. heterophylla adventitious roots on the basis of LC-MS(n) analysis. The culture conditions of adventitious roots were optimized, and datasets were subjected to a partial least squares discriminant analysis (PLS-DA), in which the growth ratio and some compounds showed a positive correlation with an aeration volume of 0.3 vvm and inoculum density of 0.15 %. Fed-batch cultivation enhanced the contents of total saponin, polysaccharides, and specific oxygen uptaker rate (SOUR). The maximum dry root weight (4.728 g l(-1)) was achieved in the 3/4 Murashige and Skoog (MS) medium group. PLS-DA showed that polysaccharides contributed significantly to the clustering of different groups and showed a positive correlation in the MS medium group. The delayed-type hypersensitivity (DTH) reaction on the mice induced by 2,4-dinitrofluorobenzene (DNFB) was applied to compare the immunocompetence effects of adventitious roots (AR) with field native roots (NR) of P. heterophylla. As a result, AR possessed a similar immunoregulation function as NR. PMID- 26137877 TI - Antioxidant Potential and Toxicity Study of the Cerium Oxide Nanoparticles Synthesized by Microwave-Mediated Synthesis. AB - Monodispersed cerium oxide nanoparticle has been synthesized by microwave mediated hydrothermal as well as microwave-mediated solvothermal synthesis. X-ray diffraction (XRD) data shows that the synthesized particles are single phase. SEM and TEM analysis suggest that particle synthesized by microwave-mediated solvothermal method are less agglomerated. In vitro toxicology study of the synthesized nanoceria particles has shown good free radical scavenging activity for NO and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical assayed except superoxide radical within a concentration range of 25 to 75 ng ml(-1). Nanoceria particle also showed inhibition of Fe-ascorbate-induced lipid peroxidation (LPx) in chick liver mitochondrial fractions. Solvothermally synthesized nanoceria showed better protection against Fe-ascorbate-induced LPx than the hydrothermal one while the hydrothermally synthesized nanoceria showed better DPPH and NO scavenging activity. The ceria nanoparticles also prevented Fe-ascorbate-H2O2-induced carbonylation of bovine serum albumin in a dose-dependent manner. At higher concentration, i.e., 100 ng ml(-1), the synthesized nanoparticles showed a reverse trend in all the parameters measured indicating its toxicity at higher doses. PMID- 26137878 TI - The EPR study of Mn(2+) ion doped DADT single crystal produced under high pressure and temperature. AB - An EPR study on Cu(2+) and VO(2+) doped di ammonium d-tartrate single crystals has been reported in previous papers, but the same host did not accept Mn(2+) ion at the same reaction conditions in previous trials. In this study EPR study of Mn(2+) ion doped di ammonium d tartrate single crystal, (DADT) [(NH4)2C4H4O6], produced in a reactor under high pressure and high temperature. The electronic transitions were determined by the optical absorption spectrum. Hyperfine splitting and g values of the Mn(2+) ion forming a complex in the lattice were measured from experimental spectra and spin-spin dipolar splitting parameters D and E were found by the spectrum simulation techniques. PMID- 26137879 TI - Associations of erythrocyte omega-3 fatty acids with biomarkers of omega-3 fatty acids and inflammation in breast tissue. AB - There is increasing evidence that chronic inflammation is associated with increased breast cancer risk. Long-chain omega-3 polyunsaturated fatty acids (LComega-3PUFA) may reduce circulating biomarkers of inflammation; however associations of blood LComega-3PUFA with breast tissue LComega-3PUFA and breast tissue biomarkers of inflammation are not well understood. We conducted a cross sectional analysis of breast tissue and blood samples from n = 85 women with no history of breast cancer, who underwent breast reduction surgery. Fatty acids of erythrocytes and undissected breast tissues were analyzed by gas chromatography; C-reactive protein (CRP), interleukin (IL)-6 and IL-8 in plasma and tissue were measured by ELISA. Multivariable-adjusted regression models were used to estimate associations between erythrocyte LComega-3PUFA and breast tissue biomarkers. Women in the highest erythrocyte LComega-3PUFA tertile had LComega-3PUFA concentrations in the breast 73% (95% CI: 31-128%; p trend < 0.0001) higher than women in the lowest tertile. Associations for each individual LComega-3PUFA were similar in magnitude. No significant association was found for the shorter omega 3 PUFA, alpha-linolenic acid. Although compatible with no association, women in the highest tertile of erythrocyte eicosapentaenoic acid had a nonsignificant 32% (95% CI: -23 to 62%) reduced breast tissue CRP. No correlation was observed between erythrocyte omega-3 PUFA and tissue IL-6 or IL-8 concentrations. Our findings provide evidence that erythrocyte omega-3 fatty acids are valid measures of breast tissue concentrations, and limited evidence that inverse associations from prospective epidemiologic studies of blood LComega-3PUFA and breast cancer risk may be partly explained by reductions in breast tissue inflammation; however, these findings require replication. PMID- 26137880 TI - New multimodal data obtained in-vivo from a single ultra-miniature transducer. AB - Recent advances in multimodal sensing technology and sensor miniaturization technologies are paving the way for a new era in physiological measurement. Traditional approaches have integrated several transducers on a single silicon chip or packaged several sensing elements within a biocompatible catheter. Thermal and electrical cross-talk between sensors, time-lag between parallel measurements, lower yields associated with the increased complexity, and restrictions on the minimum size are challenges presented by these approaches. We present an alternative method which enables simultaneous measurement of temperature, pressure and heart rate to be obtained from a single ultra-miniature solid-state transducer. For the first time multimodal data were obtained from the sensor located within the abdominal aortas of five rats. The catheter-tip sensor interfaces with a fully implanted and inductively powered telemetry device capable of operating for the lifetime of the animal. Results of this study demonstrate good agreement between the core-temperature measurement from the catheter-tip sensor and the reference sensor with mean difference between the two sensors of 0.03 degrees C +/- 0.02 degrees C (n = 5, 7 days). Real-time data obtained in the undisturbed rat, revealed fluctuations associated with the rest activity cycle, in temperature, mean arterial pressure and heart rate. The stress response was shown to elicit an elevation in the core temperature of 1.5 degrees C. This was heralded by an elevation in mean arterial pressure of 35 mmHg and heart rate of 160 bpm. Obtaining multiple parameters from a single transducer goes a considerable way towards overcoming challenges of the prior art. PMID- 26137881 TI - Cost-effectiveness of first-line erlotinib in patients with advanced non-small cell lung cancer unsuitable for chemotherapy. AB - OBJECTIVE: To assess the cost-effectiveness of erlotinib versus supportive care (placebo) overall and within a predefined rash subgroup in elderly patients with advanced non-small-cell lung cancer who are unfit for chemotherapy and receive only active supportive care due to their poor performance status or presence of comorbidities. SETTING: Between 2005 and 2009, a total of 670 patients with non small cell lung cancer (NSCLC) were randomised across 78 hospital sites (centres) in the UK. PARTICIPANTS: 670 patients with pathologically confirmed stage IIIb-IV NSCLC, unfit for chemotherapy, predominantly poor performance status (>2 on Eastern Cooperative Oncology Group, ECOG) and estimated life expectancy of at least 8 weeks. Patients were followed until disease progression or death, including a subgroup of patients who developed first cycle rash. INTERVENTIONS: Patients were randomised (1:1) to receive best supportive care plus oral placebo or erlotinib (150 mg/day) until disease progression, toxicity or death. PRIMARY OUTCOME: Overall survival (OS). SECONDARY OUTCOMES: Progression-free survival (PFS), tumour response and quality adjusted life years (QALY), including within prespecified subgroups. RESULTS: The mean incremental cost per QALY in all patients was L202,571/QALY. The probability of cost-effectiveness of erlotinib in all patients was <10% at thresholds up to L100,000. However, within the rash subgroup, the incremental cost/QALY was L56,770/QALY with a probability of cost effectiveness of about 80% for cost-effectiveness thresholds between L50,000 to L60,000. CONCLUSIONS: Erlotinib has about 80% chance of being cost-effective at thresholds between L50,000-L60,000 in a subset of elderly poor performance patients with NSCLC unfit for chemotherapy who develop first cycle (28 days) rash. Erlotinib is potentially cost-effective for this population, for which few treatment options apart from best supportive care are available. TRIAL REGISTRATION NUMBER: (ISCRTN): 77383050. PMID- 26137882 TI - Burden and trend analysis of injury mortality in China among children aged 0-14 years from 2004 to 2011. AB - OBJECTIVE: To track changes of the burden and trends of childhood injury mortality among children aged 0-14 years in China from 2004 to 2011. DESIGN: National representative data from the Chinese Disease Surveillance Points system and Chinese Maternal and Child Mortality Surveillance system from 2004 to 2011 were used. Rates and 95% CIs of aged-standardised mortality, as well as the proportions of injury death, were estimated. SETTING: Urban and rural China. PARTICIPANTS: Children aged 0-14 years from 2004 to 2011. RESULTS: The proportion of injury among all deaths in children increased from 18.69% in 2004 to 21.26% in 2011. A 'V' shape change was found in the age-standardised injury mortality rate during the study period among the children aged 0-14 years, with the age standardised injury mortality rate decreasing from 29.71 per 100,000 per year in 2004 to 24.12 in 2007, and then increasing to 28.12 in 2011. A similar change was observed in the rural area. But the age-standardised mortality rate decreased consistently in the urban area. The rate was higher among boys than among girls. Drowning, road traffic accidents and falls were consistently the top three causes of death among children. CONCLUSIONS: Childhood injury is an increasingly serious public health problem in China. The increasing trend of childhood injury mortality is driven by the rural areas rather than urban areas. More effective strategies and measures for injury prevention and control are needed for rural areas, boys, drowning, road traffic accidents and falls. PMID- 26137883 TI - Development and validation of Australian aphasia rehabilitation best practice statements using the RAND/UCLA appropriateness method. AB - OBJECTIVES: To develop and validate a national set of best practice statements for use in post-stroke aphasia rehabilitation. DESIGN: Literature review and statement validation using the RAND/UCLA Appropriateness Method (RAM). PARTICIPANTS: A national Community of Practice of over 250 speech pathologists, researchers, consumers and policymakers developed a framework consisting of eight areas of care in aphasia rehabilitation. This framework provided the structure for the development of a care pathway containing aphasia rehabilitation best practice statements. Nine speech pathologists with expertise in aphasia rehabilitation participated in two rounds of RAND/UCLA appropriateness ratings of the statements. Panellists consisted of researchers, service managers, clinicians and policymakers. MAIN OUTCOME MEASURES: Statements that achieved a high level of agreement and an overall median score of 7-9 on a nine-point scale were rated as 'appropriate'. RESULTS: 74 best practice statements were extracted from the literature and rated across eight areas of care (eg, receiving the right referrals, providing intervention). At the end of Round 1, 71 of the 74 statements were rated as appropriate, no statements were rated as inappropriate, and three statements were rated as uncertain. All 74 statements were then rated again in the face-to-face second round. 16 statements were added through splitting existing items or adding new statements. Seven statements were deleted leaving 83 statements. Agreement was reached for 82 of the final 83 statements. CONCLUSIONS: This national set of 82 best practice statements across eight care areas for the rehabilitation of people with aphasia is the first to be validated by an expert panel. These statements form a crucial component of the Australian Aphasia Rehabilitation Pathway (AARP) (http://www.aphasiapathway.com.au) and provide the basis for more consistent implementation of evidence-based practice in stroke rehabilitation. PMID- 26137884 TI - Using simplified peer review processes to fund research: a prospective study. AB - OBJECTIVE: To prospectively test two simplified peer review processes, estimate the agreement between the simplified and official processes, and compare the costs of peer review. DESIGN, PARTICIPANTS AND SETTING: A prospective parallel study of Project Grant proposals submitted in 2013 to the National Health and Medical Research Council (NHMRC) of Australia. The official funding outcomes were compared with two simplified processes using proposals in Public Health and Basic Science. The two simplified processes were: panels of 7 reviewers who met face-to face and reviewed only the nine-page research proposal and track record (simplified panel); and 2 reviewers who independently reviewed only the nine-page research proposal (journal panel). The official process used panels of 12 reviewers who met face-to-face and reviewed longer proposals of around 100 pages. We compared the funding outcomes of 72 proposals that were peer reviewed by the simplified and official processes. MAIN OUTCOME MEASURES: Agreement in funding outcomes; costs of peer review based on reviewers' time and travel costs. RESULTS: The agreement between the simplified and official panels (72%, 95% CI 61% to 82%), and the journal and official panels (74%, 62% to 83%), was just below the acceptable threshold of 75%. Using the simplified processes would save $A2.1-$A4.9 million per year in peer review costs. CONCLUSIONS: Using shorter applications and simpler peer review processes gave reasonable agreement with the more complex official process. Simplified processes save time and money that could be reallocated to actual research. Funding agencies should consider streamlining their application processes. PMID- 26137885 TI - Collecting and Analyzing Patient Experiences of Health Care From Social Media. AB - BACKGROUND: Social Media, such as Yelp, provides rich information of consumer experience. Previous studies suggest that Yelp can serve as a new source to study patient experience. However, the lack of a corpus of patient reviews causes a major bottleneck for applying computational techniques. OBJECTIVE: The objective of this study is to create a corpus of patient experience (COPE) and report descriptive statistics to characterize COPE. METHODS: Yelp reviews about health care-related businesses were extracted from the Yelp Academic Dataset. Natural language processing (NLP) tools were used to split reviews into sentences, extract noun phrases and adjectives from each sentence, and generate parse trees and dependency trees for each sentence. Sentiment analysis techniques and Hadoop were used to calculate a sentiment score of each sentence and for parallel processing, respectively. RESULTS: COPE contains 79,173 sentences from 6914 patient reviews of 985 health care facilities near 30 universities in the United States. We found that patients wrote longer reviews when they rated the facility poorly (1 or 2 stars). We demonstrated that the computed sentiment scores correlated well with consumer-generated ratings. A consumer vocabulary to describe their health care experience was constructed by a statistical analysis of word counts and co-occurrences in COPE. CONCLUSIONS: A corpus called COPE was built as an initial step to utilize social media to understand patient experiences at health care facilities. The corpus is available to download and COPE can be used in future studies to extract knowledge of patients' experiences from their perspectives. Such information can subsequently inform and provide opportunity to improve the quality of health care. PMID- 26137886 TI - Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines. AB - The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID- 26137887 TI - Maternal exposure to ambient PM2.5 and term low birthweight in the State of Georgia. AB - A growing body of evidence suggests that ambient air pollution could be associated with low birthweight (LBW). In this study, we examined pregnancy exposure to ambient PM2.5 and the risk of LBW in the State of Georgia. The study population consisted of 48,172 full-term live births between 1 January 2004 and 31 December 2004 in nine counties of Georgia, which was obtained from the national natality dataset. County-level air quality index data obtained from the U.S. Environmental Protection Agency was used to estimate exposure to ambient levels of PM2.5. Multivariate logistic regression revealed that infants with maternal exposure to PM2.5 falling within 75 to < 95th percentiles were at increased risk of LBW (OR: 1.36; 95% CI: 1.03, 1.79), after adjusting for potential confounders. This study provided more evidence on the role of PM2.5 in LBW. Reducing exposure for pregnant women would be necessary to improve the health of infants. PMID- 26137888 TI - Editor's perspectives - July 2015. PMID- 26137889 TI - Non-invasive imaging of cellulose microfibril orientation within plant cell walls by polarized Raman microspectroscopy. AB - Cellulose microfibrils represent the major scaffold of plant cell walls. Different packing and orientation of the microfibrils at the microscopic scale determines the macroscopic properties of cell walls and thus affect their functions with a profound effect on plant survival. We developed a polarized Raman microspectroscopic method to determine cellulose microfibril orientation within rice plant cell walls. Employing an array of point measurements as well as area imaging and subsequent Matlab-assisted data processing, we were able to characterize the distribution of cellulose microfibril orientation in terms of director angle and anisotropy magnitude. Using this approach we detected differences between wild type rice plants and the rice brittle culm mutant, which shows a more disordered cellulose microfibril arrangement, and differences between different tissues of a wild type rice plant. This novel non-invasive Raman imaging approach allows for quantitative assessment of cellulose fiber orientation in cell walls of herbaceous plants, an important advancement in cell wall characterization. PMID- 26137890 TI - Collective cell migration: guidance principles and hierarchies. AB - Collective cell migration results from the establishment and maintenance of collective polarization, mechanocoupling, and cytoskeletal kinetics. The guidance of collective cell migration depends on a reciprocal process between cell intrinsic multicellular organization with leader-follower cell behavior and results in mechanosensory integration of extracellular guidance cues. Important guidance mechanisms include chemotaxis, haptotaxis, durotaxis, and strain-induced mechanosensing to move cell groups along interfaces and paths of least resistance. Additional guidance mechanisms steering cell groups during specialized conditions comprise electrotaxis and passive drift. To form higher order cell and tissue structures during morphogenesis and cancer invasion, these guidance principles act in parallel and are integrated for collective adaptation to and shaping of varying tissue environments. We review mechanochemical and electrical inputs and multiparameter signal integration underlying collective guidance, decision making, and outcome. PMID- 26137891 TI - Factors affecting the tuberculosis risk in patients receiving anti-tumor necrosis factor-alpha treatment. AB - BACKGROUND: Tumor necrosis factor (TNF)-alpha inhibitors are known to increase the risk of tuberculosis (TB). OBJECTIVES: To examine the factors associated with an increased risk of TB in patients receiving anti-TNF-alpha treatment (aTNF alpha-T). METHOD: Of 3,094 patients who received aTNF-alpha-T between 2003 and 2013, a total of 1,964 subjects with a follow-up time longer than 6 months were identified and included in this retrospective analysis. Potential risk factors for the development of TB in patients receiving aTNF-alpha-T were evaluated. RESULTS: Of the 1,964 patients, 1,009 (51%) were male and 955 (49%) were female, with a mean age of 39.7 +/- 13.9 years. The primary conditions requiring aTNF alpha-T included ankylosing spondylitis (n = 875), rheumatoid arthritis (n = 711), Behcet's disease (n = 83), and others (n = 295). Sixteen patients [8 (50%) males and 8 (50%) females; 5 (31.2%) with pulmonary TB and 11 (68.8%) with extrapulmonary TB] developed TB, with a corresponding TB incidence of 466/100,000. No significant associations were found between age, gender, smoking history, pack-years of smoking, isoniazid (INH) chemoprophylaxis, type of anti TNF-alpha agent, use of other immunosuppressive drugs, and the risk of TB (p > 0.05). Multivariate logistic regression analysis showed a significantly higher risk of TB in patients diagnosed with Behcet's disease, and a significantly lower risk of TB in patients with a tuberculin skin test wheal >=10 mm in diameter (p < 0.05). CONCLUSION: aTNF-alpha-T is associated with an increased risk of pulmonary or extrapulmonary TB, even when follow-up protocols and INH chemoprophylaxis are implemented, and TB often develops in the later stages of treatment. The risk of TB was higher in patients with Behcet's disease and lower in patients who had a strong tuberculin skin test reaction. PMID- 26137893 TI - NMR structural assignments for four new 6-methoxy-tetrahydro-beta-carboline derivatives. PMID- 26137892 TI - Effect of non-surgical periodontal treatment on glycemic control of patients with diabetes: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: The present study aimed at investigating whether non-surgical periodontal treatment can reduce the Haemoglobin A1c (HbA1c) % level in type 2 diabetic patients. METHODS: A search of the literature on English publications was performed in Cochrane Central, Medline, ISI Web of Knowledge and EMBASE (until 06 February 2014). An RCT was selected if the subject was type 2 diabetic patients diagnosed with chronic periodontitis, and compared HbA1c% change after non-surgical periodontal treatment alone for at least three months of the study duration. Weighted mean difference for pooled data and large sample size strata were calculated. Heterogeneity and publication bias were explored. RESULTS: After the study selection process, only 9 RCTs were suitable. Compared to the control group, the pooled analysis (n=1082) showed -0.27% (95% CI:-0.46% to -0.07%, p = 0.007) absolute difference in HbA1c % with treatment while studies with sufficient sample size had HbA1c% change of -0.014% (95% CI:-0.18% to 0.16%, p = 0.87). Publication bias was marginally significant with Egger's teat (p=0.045) but not with Begg's test (p=0.72). CONCLUSION: The moderate reduction in HbA1c after the non-surgical therapy in patients with type 2 diabetes is consistent with previous systematic reviews. However, more large scale and high-quality RCTs are necessitated to confirm these results. PMID- 26137894 TI - Precision in psychiatry. PMID- 26137895 TI - CT scan range estimation using multiple body parts detection: let PACS learn the CT image content. AB - PURPOSE: The aim of this study was to develop an efficient CT scan range estimation method that is based on the analysis of image data itself instead of metadata analysis. This makes it possible to quantitatively compare the scan range of two studies. METHODS: In our study, 3D stacks are first projected to 2D coronal images via a ray casting-like process. Trained 2D body part classifiers are then used to recognize different body parts in the projected image. The detected candidate regions go into a structure grouping process to eliminate false-positive detections. Finally, the scale and position of the patient relative to the projected figure are estimated based on the detected body parts via a structural voting. The start and end lines of the CT scan are projected to a standard human figure. The position readout is normalized so that the bottom of the feet represents 0.0, and the top of the head is 1.0. RESULTS: Classifiers for 18 body parts were trained using 184 CT scans. The final application was tested on 136 randomly selected heterogeneous CT scans. Ground truth was generated by asking two human observers to mark the start and end positions of each scan on the standard human figure. When compared with the human observers, the mean absolute error of the proposed method is 1.2% (max: 3.5%) and 1.6% (max: 5.4%) for the start and end positions, respectively. CONCLUSION: We proposed a scan range estimation method using multiple body parts detection and relative structure position analysis. In our preliminary tests, the proposed method delivered promising results. PMID- 26137896 TI - A computational approach to calculate personalized pennation angle based on MRI: effect on motion analysis. AB - PURPOSE: Muscles are the primary component responsible for the locomotion and change of posture of the human body. The physiologic basis of muscle force production and movement is determined by the muscle architecture (maximum muscle force, [Formula: see text], optimal muscle fiber length, [Formula: see text], tendon slack length, [Formula: see text], and pennation angle at optimal muscle fiber length, [Formula: see text]). The pennation angle is related to the maximum force production and to the range of motion. The aim of this study was to investigate a computational approach to calculate subject-specific pennation angle from magnetic resonance images (MRI)-based 3D anatomical model and to determine the impact of this approach on the motion analysis with personalized musculoskeletal models. METHODS: A 3D method that calculates the pennation angle using MRI was developed. The fiber orientations were automatically computed, while the muscle line of action was determined using approaches based on anatomical landmarks and on centroids of image segmentation. Three healthy male volunteers were recruited for MRI scanning and motion capture acquisition. This work evaluates the effect of subject-specific pennation angle as musculoskeletal parameter in the lower limb, focusing on the quadriceps group. A comparison was made for assessing the contribution of personalized models on motion analysis. Gait and deep squat were analyzed using neuromuscular simulations (OpenSim). RESULTS: The results showed variation of the pennation angle between the generic and subject-specific models, demonstrating important interindividual differences, especially for the vastus intermedius and vastus medialis muscles. The pennation angle variation between personalized and generic musculoskeletal models generated significant variation in muscle moments and forces during dynamic motion analysis. CONCLUSIONS: A MRI-based approach to define subject-specific pennation angle was proposed and evaluated in motion analysis models. The significant differences obtained for the moments and muscle forces in quadriceps muscles indicate that a personalized approach in modeling the pennation angle can provide more individual details when investigating motion behaviors in specific subjects. PMID- 26137897 TI - Influence of relative blood flow restriction pressure on muscle activation and muscle adaptation. AB - INTRODUCTION: The aim of this study was to investigate the acute and chronic skeletal muscle response to differing levels of blood flow restriction (BFR) pressure. METHODS: Fourteen participants completed elbow flexion exercise with pressures from 40% to 90% of arterial occlusion. Pre/post torque measurements and electromyographic (EMG) amplitude of each set were quantified for each condition. This was followed by a separate 8-week training study of the effect of high (90% arterial occlusion) and low (40% arterial occlusion) pressure on muscle size and function. RESULTS: For the acute study, decreases in torque were similar between pressures [-15.5 (5.9) Nm, P = 0.344]. For amplitude of the first 3 and last 3 reps there was a time effect. After training, increases in muscle size (10%), peak isotonic strength (18%), peak isokinetic torque (180 degrees /s = 23%, 60 degrees /s = 11%), and muscular endurance (62%) changed similarly between pressures. CONCLUSION: We suggest that higher relative pressures may not be necessary when exercising under BFR. PMID- 26137898 TI - Numeric score-based conditional and overall change-in-status indices for ordered categorical data. AB - Planned interventions and/or natural conditions often effect change on an ordinal categorical outcome (e.g., symptom severity). In such scenarios, it is sometimes desirable to assign a priori scores to observed changes in status, typically giving higher weight to changes of greater magnitude. We define change indices for such data based upon a multinomial model for each row of a c * c table, where the rows represent the baseline status categories. We distinguish an index designed to assess conditional changes within each baseline category from two others designed to capture overall change. One of these overall indices measures expected change across a target population. The other is scaled to capture the proportion of total possible change in the direction indicated by the data, so that it ranges from -1 (when all subjects finish in the least favorable category) to +1 (when all finish in the most favorable category). The conditional assessment of change can be informative regardless of how subjects are sampled into the baseline categories. In contrast, the overall indices become relevant when subjects are randomly sampled at baseline from the target population of interest, or when the investigator is able to make certain assumptions about the baseline status distribution in that population. We use a Dirichlet-multinomial model to obtain Bayesian credible intervals for the conditional change index that exhibit favorable small-sample frequentist properties. Simulation studies illustrate the methods, and we apply them to examples involving changes in ordinal responses for studies of sleep deprivation and activities of daily living. PMID- 26137899 TI - CO2 laser treatment of tracheal stenosis. AB - CONCLUSION: Delivery of a carbon dioxide laser is an effective method and can be used in selected cases of tracheal stenosis. OBJECTIVES: To present retrospective experience in tracheal stenosis of 16 patients treated by bronchoscopic delivery of carbon dioxide laser, considering the characteristics of the treated stenosis, surgical procedures performed, and post-operative outcomes and complications. METHODS: All demographic and clinical data were collected retrospectively. Chest and neck computed tomography scans were performed to assess the stenosis, including length, location, and glottic involvement. The stenotic area was evaluated endoscopically according to an adapted Meyer and Cotton grading scale. RESULTS: The aetiology of the tracheal stenosis was intubation-related in 14 cases, and idiopathic in two cases. The duration of intubation ranged between 1 hour to 26 days. According to the Myers-Cotton classification, mean stage of stenosis for the study group was 3.3 +/- 0.5. Mean length of the stenosis was 23.75 +/- 6.95 (range = 15-40) mm. Mean follow-up for the study group was 23.81 +/- 7.11 (range = 12-38) months. Postoperative decannulation was achieved in 13 patients (81.3%), and decannulation was not achieved in three patients (18.7%). PMID- 26137900 TI - Mercury Concentrations in Birds from Two Atmospherically Contaminated Sites in North Texas, USA. AB - Mercury (Hg) is a ubiquitous and highly toxic contaminant that can have negative effects on wildlife. Only a few studies have measured Hg concentrations in birds from the south central United States, and the potential threat of Hg contamination to birds in this region is largely unknown. In the present study, we assess Hg concentrations in blood and feathers from five bird species [eastern bluebird (Sialis sialis), Carolina wren (Thryothorus ludovicianus), wood duck (Aix sponsa), great egret (Ardea alba), and great blue heron (Ardea herodias)] that occupy different trophic levels at Caddo Lake and Lewisville Lake, located in northeast and north central Texas, respectively. Both sites are contaminated with Hg from the atmosphere. Adult passerines had higher Hg concentrations in their blood than conspecific nestlings. Mercury concentrations in feathers differed between species by more than an order of magnitude with large piscivorous species having higher concentrations than smaller insectivorous species. Mercury concentrations in eastern bluebirds were higher at Caddo Lake than Lewisville Lake. The present study represents one of the first studies of Hg concentrations in multiple bird species in north Texas and suggests that Hg concentrations in birds from atmospherically polluted sites in this region may be high enough to compromise fitness in those species. PMID- 26137901 TI - Impact of Overlapping Functional Gastrointestinal Disorders on the Presentation and Quality of Life of Patients with Erosive Esophagitis and Nonerosive Reflux Disease. AB - OBJECTIVE: The aim of this study was to investigate the impact of overlapping functional gastrointestinal disorder (FGID) on the quality of life of patients with nonerosive reflux disease (NERD) and erosive esophagitis (EE). MATERIALS AND METHODS: Data from patients with NERD and EE were collected between January 2009 and March 2010. These cases were further stratified into the subgroups of overlapping NERD-functional dyspepsia (FD), NERD-irritable bowel syndrome (IBS), EE-FD, EE-IBS, and NERD or EE alone according to the symptoms. All patients completed the modified Chinese GERDQ and the SF-36 questionnaires. RESULTS: Of the 222 enrolled patients, 96 (43.2%) had NERD and 126 (56.8%) had EE. Overlap of FGID occurred in 43.8-45.8% of the NERD patients, and in 41.3-44.4% of EE cases. The impact of overlapping FGID on patient quality of life was greater in the patients with overlapping NERD-FD compared to those with NERD alone (mean SF-36 total scores 59 vs. 72, adjusted p = 0.025) and the cases with overlapping EE-FD compared to those with EE alone (mean SF-36 total scores 53.19 vs. 73.11, adjusted p = 0.047). There were no significant differences between the individuals with overlapping NERD/EE-IBS and those with NERD/EE alone. CONCLUSIONS: There was a high prevalence of overlapping FGID, with both FD and IBS, among the GERD patients. The individuals with overlapping GERD and FD had lower quality of life scores than those with GERD alone. PMID- 26137902 TI - Computerized analysis of calcification of thyroid nodules as visualized by ultrasonography. AB - OBJECTIVE: The purpose of this study is to quantify computerized calcification features from ultrasonography (US) images of thyroid nodules in order to determine the ability to differentiate between malignant and benign thyroid nodules. METHODS: We designed and implemented a computerized analysis scheme to quantitatively analyze the US features of the calcified thyroid nodules from 99 pathologically determined calcified thyroid nodules. Univariate analysis was used to identify features that were significantly associated with tumor malignancy, and neural-network analysis was performed to classify tumors as benign or malignant. The diagnostic performance of the neural network was evaluated using receiver operating characteristic (ROC) analysis, where in the area under the ROC curve (Az) summarized the diagnostic performance of specific calcification features. RESULTS: The performance values for each calcification feature were as follows: ratio of calcification distance=0.80, number of calcifications=0.68, skewness=0.82, and maximum intensity=0.75. The combined value of the four features was 0.84.With a threshold of 0.64, the Az value of calcification features was 0.83 with a sensitivity of 83.0%, specificity of 82.4%, and accuracy of 82.8%. CONCLUSIONS: These results support the clinical feasibility of using computerized analysis of calcification features from thyroid US for differentiating between malignant and benign nodules. PMID- 26137903 TI - Percutaneous treatment of symptomatic superior mesenteric vein stenosis using self-expanding nitinol stents. AB - PURPOSE: To evaluate the technical and clinical success of percutaneous superior mesenteric vein (SMV) stenting in symptomatic patients using self-expanding nitinol stents. METHODS: We retrospectively analyzed the technical and clinical success of percutaneous SMV stenting of 6 symptomatic patients (3 men, mean age 67 years, range 48-81 years). Stenosis of the SMV was caused by postoperative stricture (n=3), pancreas carcinoma (n=1) and pancreatitis (n=2). As a result of the stenosis, 3 patients had symptomatic ascites, 2 patients showed signs of mesenteric ischemia and 1 patient had recurrent gastrointestinal bleeding. Stenting was performed by a percutaneous transhepatic approach using self expanding nitinol stents. RESULTS: Stenting of the SMV was technically and clinically successful in all patients. No peri-interventional complications occurred. The stent diameters ranged from 6 to 14 mm. During the mean follow-up of 6 months (range, 2-10 months) 1 patient presented early stent occlusion 2 weeks after placement. CONCLUSION: Stenting of a symptomatic SMV stenosis using self-expanding nitinol stents is feasible and clinically effective. PMID- 26137904 TI - Evaluation of the European Society of Urogenital Radiology (ESUR) PI-RADS scoring system for assessment of extra-prostatic extension in prostatic carcinoma. AB - INTRODUCTION: To evaluate extra-prostatic extension (EPE) comparing PI-RADS to non-standardized reporting. MATERIALS AND METHODS: With IRB approval, 145 consecutive patients underwent radical prostatectomy (RP) and multi-parametric (T2W+DWI+DCE) MRI between 2012 and 2013. Eighty patients (66.3% with EPE) were staged without PI-RADS and 65 patients (64.6% with EPE) were staged using a 5 point PI-RADS scoring system. Studies were reported by fellowship-trained radiologists in routine clinical practice. Individual PIRADS scores were assessed using ROC to determine the score which optimized sensitivity/specificity. Diagnostic accuracy for EPE was compared with/without PI-RADS using the McNemar test. Subgroup analysis by radiologist experience was performed using Spearman correlation and chi-square. RESULTS: Area under ROC curve for EPE using PI-RADS was 0.62 and optimal sensitivity/specificity was achieved with PI-RADS score >= 3. Compared to non-standardized reporting, sensitivity for EPE improved with PI RADS (59.5% [49.1-68.2] vs. 24.5% [16.7-31.2]), p=0.01; with no difference in specificity (68.0% [50.5-82.6]) vs. (75.0% [60.1-87.6]), p=0.06. Overall accuracy improved with PI-RADS (62.7% [49.6-73.6] vs. 42.0% [31.7-50.7%]), p=0.006. Diagnostic accuracy was better among experienced radiologists without PI-RADS (p=0.005); however, there was no difference in accuracy by reader experience using PI-RADS (p=0.24). CONCLUSION: The PI-RADS criteria for EPE improves sensitivity without reducing specificity. PI-RADS may reduce differences in accuracy by reader experience. PMID- 26137905 TI - Technical prerequisites and imaging protocols for CT perfusion imaging in oncology. AB - The aim of this review article is to define the technical prerequisites of modern state-of-the-art CT perfusion imaging in oncology at reasonable dose levels. The focus is mainly on abdominal and thoracic tumor imaging, as they pose the largest challenges with respect to attenuation and patient motion. We will show that low kV dynamic scanning in conjunction with detection technology optimized for low photon fluxes has the highest impact on reducing dose independently of other choices made in the protocol selection. We discuss, derived from relatively simple first principles, on what appropriate temporal sampling and total scan duration depend on and why optimized contrast medium injection protocols are also essential in limiting dose. Finally we will examine the possibility of simultaneously extracting standard morphological and functional information from one single 4D examination as a potential enabler for a more widespread use of dynamic contrast enhanced CT in oncology. PMID- 26137906 TI - A Review of the History of Attitudes Toward Drinking in Pregnancy. AB - BACKGROUND: It is now well accepted in pediatrics and obstetrics that prenatal alcohol is a teratogenic agent and the primary causative factor underlying fetal alcohol spectrum disorders (FASDs), although for the majority of the 20th century that knowledge was either unknown or ignored. At least 2 factors contributed to the delay in recognizing alcohol's role in teratogenicity: the rejection of earlier evidence pertaining to alcohol and pregnancy following the repeal of Prohibition in the United States, Canada, and several European countries; and misinterpretation of earlier research findings in a eugenic rather than toxicological context. The pervasive belief held well into the 1970s that there was no risk to either mother or fetus from prenatal alcohol posed a major challenge to changing physician and public attitudes on alcohol and pregnancy. This review provides insight on key events that occurred in changing physician and public understanding of the risks posed by prenatal alcohol use in pregnancy. METHODS: Historical review of events primarily in the U.S. federal government, found in referenced documents. RESULTS: The transition in physician and public understanding of the risks posed by prenatal alcohol use was aided by the existence of National Institute on Alcohol Abuse and Alcoholism (NIAAA) which was created in 1971. This government agency was able to support research on alcohol and pregnancy immediately following the 1973 published clinical reports calling attention to a proposed fetal alcohol syndrome (FAS). These early research studies provided the foundation for the first government health advisory on alcohol and pregnancy, issued by NIAAA in 1977. Subsequently, the U.S. Food and Drug Administration (FDA) used this new knowledge on FAS in their effort to add alcoholic beverages to the range of products with ingredient and consumer information labeling. The ensuing hearings and actions resulted in a new health advisory under the auspices of the Surgeon General, encouraging avoidance of alcohol consumption in pregnancy. In subsequent years, Congressional attention to the FAS issue resulted in the Alcoholic Beverage Labeling Law. CONCLUSIONS: The pace at which understanding of the risks of prenatal alcohol moved forward from a total misunderstanding to acceptance was aided by both the efforts of the NIAAA in its support of research, and the FDA in its efforts to improve consumer information. Today, many women in the United States as well as other countries continue to ignore advisories on avoiding alcohol consumption in pregnancy, emphasizing the need for persistence in education on these health risks. PMID- 26137907 TI - A potential role for 6-sulfo sialyl Lewis X in metastasis of bladder urothelial carcinoma. AB - OBJECTIVES: It is widely accepted that sialyl Lewis X (sLeX) and sialyl Lewis A (sLeA, also known as CA 19-9) glycans expressed on cancer cells function in E selectin-mediated metastasis. Recently, it was reported that 6-sulfo sLeX glycans detected by the MECA-79 monoclonal antibody are expressed in roughly a quarter of gastric adenocarcinoma cases, and that these cases show a poorer prognosis than MECA-79-negative cases do. The present study was undertaken to assess expression of 6-sulfo sLeX glycans in bladder urothelial carcinoma and evaluate potential clinical implications. MATERIALS AND METHODS: We analyzed 78 specimens representing bladder urothelial carcinoma, as well as 4 bladder urothelial carcinoma cell lines, by immunostaining with a battery of anticarbohydrate antibodies. We also undertook an E-selectin.IgM chimera binding assay to assess E selectin binding to 6-sulfo sLeX expressed on bladder urothelial carcinoma cells and performed reverse transcription polymerase chain reaction and complementary DNA transfection to determine which N-acetylglucosamine-6-O-sulfotransferases function in 6-sulfo sLeX biosynthesis in those cells. Finally, we performed double-immunofluorescence staining for MECA-79 and either CD3 or CD8 to evaluate potential association between high endothelial venule (HEV)-like vessels and tumor-infiltrating T lymphocytes. RESULTS: 6-Sulfo sLeX glycans were expressed in ~20% of bladder urothelial carcinoma cases, particularly in plasmacytoid and micropapillary variants. Positive cells were also bound by E-selectin.IgM chimeras in a calcium-dependent manner. Transcripts encoding N-acetylglucosamine 6-O-sulfotransferase-2 were detected preferentially in HT-1197 bladder urothelial carcinoma cells expressing 6-sulfo sLeX, and transfection of the enzyme complementary DNA into HT-1376 cells, which do not express 6-sulfo sLeX glycans, resulted in cell surface expression of 6-sulfo sLeX. Furthermore, 6-sulfo sLeX glycans were expressed in HEV-like vessels induced in and around lymphocyte aggregates formed near carcinoma cell nests. These HEV-like vessel-associated tumor-infiltrating lymphocytes were composed primarily of CD3(+) T cells, with a fraction of CD8(+) cytotoxic T cells. CONCLUSIONS: Our findings indicate that 6 sulfo sLeX glycans likely play 2 roles in bladder urothelial carcinoma progression: one in lymphocyte recruitment to enhance antitumor immune responses, and the other in E-selectin-mediated tumor cell adhesion to vascular endothelial cells, which is potentially associated with metastasis. PMID- 26137908 TI - Haemoglobin levels correlates with the presence of coronary artery disease. AB - RATIONALE, AIMS AND OBJECTIVES: Although the condition of low haemoglobin (Hb) levels has been established as a risk factor in the development of coronary artery disease (CAD), it is still a debate particularly in patients with angiographically documented disease. In the present study, we sought to identify the relationship between Hb levels and the presence of CAD. METHODS: The study consisted of 356 consecutive patients referred for elective coronary angiography (CAG). Exclusion criteria included a history of prior MI within last 3 months, presence of neoplastic disorders or any inflammatory diseases or overt diabetes mellitus. Blood samples for haematologic and biochemical measurements were collected on admission following at least 12 hours of overnight fasting. Patients were divided into four groups based on the quartiles of Hb (quartile I < 13.50 g/dL, quartile II 13.50-14.70 g/dL, quartile III 14.71-15.74 g/dL, quartile IV > 15.74 g/dL). Additionally, patients filled out a questionnaire of asking their brief medical histories and baseline characteristics. RESULTS: Lower Hb quartiles were independently related to the presence of CAD in subjects who were referred to elective CAG. The patients with older age [P = 0.008, odds ratio (OR) = 1.042], male gender (P = 0.007, OR = 3.408), in quartile I (P = 0.003, OR = 5.697), in quartile II (P < 0.001, OR = 8.767), in quartile III (P = 0.011, P = 3.076), higher white blood cells count (P = 0.037, OR = 1.208), lower platelet count (P = 0.049, OR = 0.995), condition of current smoker (P = 0.030, OR = 2.548), higher value of fasting glucose (P = 0.014, OR = 1.038), estimated glomerular filtration rate < 60 (mL/min/1.73 m(2) ; P = 0.004, OR = 3.269) were more likely associated with the risk of the presence of CAD. CONCLUSIONS: The present study revealed that lower quartiles of Hb levels were independently related to the presence of CAD in subjects who were referred to elective CAG. Hb levels, which can be measured easily in almost all medical centres, may be considered as a potential predictor for the presence of CAD in patients at high risk for CAD. PMID- 26137909 TI - Local interspecies introgression is the main cause of extreme levels of intraspecific differentiation in mussels. AB - Structured populations, and replicated zones of contact between species, are an ideal opportunity to study regions of the genome with unusual levels of differentiation; and these can illuminate the genomic architecture of species isolation, and the spread of adaptive alleles across species ranges. Here, we investigated the effects of gene flow on divergence and adaptation in the Mytilus complex of species, including replicated parental populations in quite distant geographical locations. We used target enrichment sequencing of 1269 contigs of a few kb each, including some genes of known function, to infer gene genealogies at a small chromosomal scale. We show that geography is an important determinant of the genomewide patterns of introgression in Mytilus and that gene flow between different species, with contiguous ranges, explained up to half of the intraspecific outliers. This suggests that local introgression is both widespread and tends to affect larger chromosomal regions than purely intraspecific processes. We argue that this situation might be common, and this implies that genome scans should always consider the possibility of introgression from sister species, unsampled differentiated backgrounds, or even extinct relatives, for example Neanderthals in humans. The hypothesis that reticulate evolution over long periods of time contributes widely to adaptation, and to the spatial and genomic reorganization of genetic backgrounds, needs to be more widely considered to make better sense of genome scans. PMID- 26137910 TI - Data Inconsistencies in the Beier et al. (2015) Article. PMID- 26137912 TI - Implications of the rising frequency of uterine rupture. PMID- 26137911 TI - Selenocystamine improves protein accumulation in chloroplasts of eukaryotic green algae. AB - Eukaryotic green algae have become an increasingly popular platform for recombinant proteins production. In particular, Chlamydomonas reinhardtii, has garnered increased attention for having the necessary biochemical machinery to produce vaccines, human antibodies and next generation cancer targeting immunotoxins. While it has been shown that chloroplasts contain chaperones, peptidyl prolylisomerases and protein disulfide isomerases that facilitate these complex proteins folding and assembly, little has been done to determine which processes serve as rate-limiting steps for protein accumulation. In other expression systems, as Escherichia coli, Chinese hamster ovary cells, and insect cells, recombinant protein accumulation can be hampered by cell's inability to fold the target polypeptide into the native state, resulting in aggregation and degradation. To determine if chloroplasts' ability to oxidize proteins that require disulfide bonds into a stable conformation is a rate-limiting step of protein accumulation, three recombinant strains, each expressing a different recombinant protein, were analyzed. These recombinant proteins included fluorescent GFP, a reporter containing no disulfide bonds; Gaussia princeps luciferase, a luminescent reporter containing disulfide bonds; and an immunotoxin, an antibody-fusion protein containing disulfide bonds. Each strain was analyzed for its ability to accumulate proteins when supplemented with selenocystamine, a small molecule capable of catalyzing the formation of disulfide bonds. Selenocystamine supplementation led to an increase in luciferase and immunotoxin but not GFP accumulation. These results demonstrated that selenocystamine can increase the accumulation of proteins containing disulfide bonds and suggests that a rate-limiting step in chloroplast protein accumulation is the disulfide bonds formation in recombinant proteins native structure. PMID- 26137914 TI - Water soluble, cyclometalated Pt(ii)-Ln(iii) conjugates towards novel bimodal imaging agents. AB - Facile conjugation of a luminescent cyclometalated Pt(II) complex with a DO3A derived Gd(III) moiety yields a hybrid species with visible luminescence and enhanced relaxivity. PMID- 26137913 TI - Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying both Ligand and siRNA. AB - Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy. PMID- 26137915 TI - Performance of a combined system of biotrickling filter and photocatalytic reactor in treating waste gases from a paint-manufacturing plant. AB - A pilot-scale biotrickling filter (BTF) was established in treating the waste gases that are intermittently produced from an automobile paint-manufacturing workshop. Results showed that the BTF required longer time to adapt to the aromatic compounds. The removal efficiencies (REs) for all aliphatic compounds reached more than 95% on day 80. Aromatic compounds were not easily removed by the BTF. The REs obtained by the BTF for toluene, ethylbenzene, m-xylene, o xylene and p-xylene on day 80 were 72.7%, 77.2%, 71.9%, 74.8% and 60.0%, respectively. A maximum elimination capacity (EC) of 13.8 g-C m(-3) h(-1) of the BTF was achieved at an inlet loading rate of 19.4 g-C m(-3) h(-1) with an RE of 72%. Glucose addition promoted the biomass accumulation despite the fact that temporal decrease of REs for aromatic compounds occurred. When the inlet loading rates exceed 11.1 g-C m(-3) h(-1), the REs of the aromatic compounds decreased by 10% to 15%. This negative effect of shock loads on the performance of the BTF can be attenuated by the pre-treatment of the photocatalytic reactor. Nearly all components were removed by the combined system with REs of 99%. PMID- 26137917 TI - Bond Strength of High-Viscosity Glass Ionomer Cements is Affected by Tubular Density and Location in Dentin? AB - This study evaluated the influence of tubular density of different dentin depths and location on the bond strength of high-viscosity glass ionomer cements (GIC). A total of 20 molars were selected and assigned into six experimental groups, considering two different high-viscosity GICs-Fuji IX (FIX) or Ketac Molar (KM), and dentin location-proximal, occlusal superficial, or occlusal deep dentin (n=10). Teeth were cut and a topographical analysis of four sections per group was performed to obtain data about the tubular density of each different dentin location and depths by laser scanning confocal microscopy (100*). Polyethylene tubes were placed over the pretreated surfaces and filled with one of the GICs. Microshear bond strength (uSBS) test was performed after storage in distilled water (24 h at 37 degrees C). Failure modes were evaluated using a stereomicroscope (400*). Multilevel regression analysis was performed to compare the results at a significance level set at 5%. The tubule density was inversely proportional to the bond strength for both GICs (p<0.05). Adhesive/mixed failure prevailed in all experimental groups. Proximal (30036.5+/-3433.3) and occlusal superficial 29665.3+/-1434.04 dentin shows lower tubule density, resulting in a better GIC bonding performance (proximal: FIX-3.61+/-1.05; KM-3.40+/-1.62; occlusal superficial: FIX-4.70+/-1.85; KM-4.97+/-1.25). Thus, we can concluded that the lowest tubule density in proximal and occlusal superficial dentin results in a better GIC bond strength performance. PMID- 26137916 TI - QoL analyses from INFORM study, a phase III study of gefitinib versus placebo as maintenance therapy in advanced NSCLC. AB - This report aimed to provide the full results of QoL assessment in INFORM study. QoL was assessed by FACT-L questionnaire. QoL improvement ratio in gefitinib arm was higher than placebo arm (FACT-L: 46% vs. 22%, p < 0.001; TOI: 41% vs. 18%, p < 0.001; LCS: 46% vs. 22%, p < 0.001). Gefitinib prolonged time-to-worsening of QoL (FACT-L: 2.8 m vs 1.4 m, p = 0.019; TOI: 3.5 m vs 1.4 m, p = 0.006; LCS: 2.8 vs 1.4 m, p = 0.028). Patients with an improvement in QoL had longer PFS (FACT-L: 9.4 m vs. 2.8 m vs. 2.7 m, P < 0.001; TOI: 9.9 m vs. 2.8 m vs. 2.1 m, P < 0.001; LCS: 9.4 m vs. 2.9 m vs. 2.1 m, P < 0.001) and OS (FACT-L: 25.4 m vs. 19.9 m vs. 14.4 m, P = 0.003; TOI: 25.7 m vs. 19.0 m vs. 12.7 m, P = 0.002; LCS: 25.4 m vs. 19.3 m vs. 14.7 m, P = 0.004) compared with patients with stable or worsened QoL. Furthermore, in patients with good QoL at baseline, the treatment of gefitinib couldn't improve OS compared to placebo, whereas patients with low QoL experienced marginal significant improvement in OS (20.6 m vs 14.4, p = 0.051). Our study indicated that gefitinib could improve patients' QoL, confirmed the prognostic value of QoL changes during treatment, and implied patients with low QoL at baseline may be the potential population which will gain OS benefit from maintenance EGFR-TKI therapy. PMID- 26137918 TI - Investigating incretin-based therapies as a novel treatment for depression in type 2 diabetes: Findings from the South London Diabetes (SOUL-D) Study. AB - We aimed to investigate the association between incretin-based therapies and 1 year change in depressive symptoms in a cohort of 1735 patients with newly diagnosed type 2 diabetes. The incretin group experienced significant reduction in depressive symptoms compared to controls. This was independent of HbA1c and may be mediated by an anti-inflammatory mechanism. PMID- 26137919 TI - Evaluation of diabetes awareness among general population of Bahawalpur, Pakistan. AB - AIMS: To evaluate diabetes awareness among general population of Bahawalpur, Pakistan. METHODS: A questionnaire based descriptive cross sectional study was performed during 2014. Descriptive and inferential statistics were applied using the IBM Statistical Package for Social Sciences version 20. RESULTS: Total 383 respondents participated in this study giving a response rate of about 88%. Mean age of the participants was 33+/-13.3 years and the majority of the participants were females (50.4%). Mean scores of the participants were 20.77+/-6.65 out of 34 and only one participant scored 34/34 marks. Kruskal-Wallis and Mann-Whitney U test revealed that females scored significantly higher diabetes awareness score than males (p<0.05). Moreover, urban residential status, better education and higher socioeconomic status were significantly associated with higher diabetes awareness. CONCLUSIONS: Majority of our study population had adequate awareness regarding diabetes. However, lack of awareness was observed among illiterate, poor and rural participants that indicated the immediate need of diabetes awareness programs for these participants. PMID- 26137920 TI - The ex vivo antiplatelet activation potential of fruit phenolic metabolite hippuric acid. AB - Polyphenol-rich fruit and vegetable intake has been associated with reduction in platelet hyperactivity, a significant contributor to thrombus formation. This study was undertaken to investigate the possible role of hippuric acid, a predominant metabolite of plant cyclic polyols, phenolic acids and polyphenols, in reduction of platelet activation-related thrombogenesis. Fasting blood samples were collected from 13 healthy subjects to analyse the effect of varying concentrations of hippuric acid (100 MUM, 200 MUM, 500 MUM, 1 mM and 2 mM) on activation-dependant platelet surface-marker expression. Procaspase activating compound-1 (PAC-1) and P-selectin/CD62P monoclonal antibodies were used to evaluate platelet activation-related conformational changes and alpha-granule release respectively using flow cytometry. Platelets were stimulated ex vivo via the P2Y1/P2Y12- adenosine diphosphate (ADP) pathway of platelet activation. Hippuric acid at a concentration of 1 mM and 2 mM significantly reduced P selectin/CD62P expression (p = 0.03 and p < 0.001 respectively) induced by ADP. Hippuric acid at 2 mM concentration also inhibited PAC-1 activation-dependant antibody expression (p = 0.03). High ex vivo concentrations of hippuric acid can therefore significantly reduce P-selectin and PAC-1 expression thus reducing platelet activation and clotting potential. However, although up to 11 mM of hippuric acid can be excreted in the urine per day following consumption of fruit, hippuric acid is actively excreted with a recorded Cmax for hippuric acid in human plasma at 250-300 MUM. This is lower than the blood concentration of 1-2 mM shown to be bioactive in this research. The contribution of hippuric acid to the protective effects of fruit and vegetable intake against vascular disorders by the pathways measured is therefore low but could be synergistic with lowered doses of antiplatelet drugs and help reduce risk of thrombosis in current antiplatelet drug sensitive populations. PMID- 26137921 TI - Successful Treatment with Ultrasound-Guided Aspiration of Intractable Methicillin Resistant Staphylococcus aureus Brain Abscess in an Extremely Low Birth Weight Infant. AB - Brain abscesses are an uncommon and devastating complication of bacteremia in extremely low birth weight infants (<1 kg). We report a 25-week preterm neonate who developed a brain abscess 4 weeks following methicillin-resistant Staphyloccocus aureus (MRSA) sepsis. A huge brain abscess was seen with routine brain sonography on day 19 of life. Despite intravenous vancomycin treatment, the brain abscess increased in size and was associated with increased intracranial pressure on day 49 of life. The brain abscess was accompanied by mild meningeal inflammation with negative blood and cerebrospinal fluid cultures. Diagnosis of abscess was confirmed by bedside ultrasound-guided aspiration, and MRSA was isolated from the pus culture. The MRSA brain abscess refractory to vancomycin was successfully treated by surgical ultrasound-guided percutaneous needle aspiration of brain abscess and prolonged courses of antibiotic administration. At the time of this report, the infant was 9 months old (corrected age was 6 months) and had normal neurodevelopment for her corrected age on the Bayley Infant Neurodevelopmental Screener. PMID- 26137922 TI - Health behavior theory constructs and smoking and cessation-related behavior among survivors of ten cancers nine years after diagnosis: A report from the American Cancer Society's Study of Cancer Survivors-I. AB - OBJECTIVE: Quitting smoking is important for cancer prognosis, but some cancer survivors continue to smoke. This study examined psychological correlates of smoking status and patterns, likelihood of quitting, and intentions to quit among long-term survivors. METHODS: Cross-sectional relationships between psychological constructs from health behavior theories (e.g., perceived risk, quitting barriers) and smoking and cessation-related behavior were examined among survivors of 10 cancers. Survivors were recruited by stratified random sampling from cancer registries in a nationwide, longitudinal, quality-of-life study (n=2938). RESULTS: Approximately 9 years post-diagnosis, survivors who currently smoke (compared with those who quit before or after diagnosis) perceived health problems caused by smoking as less severe, perceived fewer benefits of quitting for cancer survivors, greater barriers to quitting, and reported more daily exposure to others' smoking. Survivors intending to quit (vs. those not intending or unsure) perceived greater risks of smoking for cancer prognosis, more severe health effects from smoking, fewer benefits of smoking, and greater social pressure to quit. Nondaily smokers had higher levels of self-efficacy and less exposure to others' smoking compared to daily smokers. CONCLUSIONS: Long-term cancer survivors' perceptions of the risks of smoking for cancer prognosis, the severity of health problems from smoking, cessation barriers, and the benefits of quitting are appropriate targets for interventions for continuing smokers. Nondaily smokers may be especially amenable to intervention. Survivors' daily exposure to others' smoking should also be addressed in treatment. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26137923 TI - Explaining Physical Activity Maintenance After a Theory-Based Intervention Among Patients With Rheumatoid Arthritis: Process Evaluation of a Randomized Controlled Trial. AB - OBJECTIVE: Regular physical activity (PA) benefits patients with rheumatoid arthritis (RA), particularly when maintained over time. Research in this area has largely focused on factors associated with initiating PA, while factors contributing to PA maintenance, particularly after lifestyle interventions, have received less attention. This study examined whether higher levels of autonomous motivation, self-efficacy for PA, and greater use of self-regulation skills mediated PA initiation and maintenance 6 months after a theory-based motivational interviewing and self-regulation coaching intervention. METHODS: Seventy-eight individuals with RA were randomized to receive either a patient-education session (control group), or the patient-education session plus 1 motivational interview and 2 self-regulation coaching sessions (treatment group). Mediation analyses examined the effects of this intervention on PA initiation and maintenance through the intermediate variables autonomous motivation, self-efficacy for PA, and use of self-regulation skills. Analyses were controlled for age, sex, and previous levels of PA. RESULTS: The treatment group reported significantly higher autonomous motivation and greater use of self-regulation skills than controls at posttreatment. Increases in PA from baseline to posttreatment were not mediated by any intermediate variables. However, maintenance of PA from posttreatment to followup (6 months later) was mediated by greater autonomous motivation and use of self-regulation skills. CONCLUSION: Greater autonomous motivation and use of self-regulation skills predict maintenance of PA following a motivational interviewing and self-regulation coaching intervention. In promoting PA among patients with RA, supporting patient autonomy and teaching self-regulation skills, which focus attention on achieving PA goals, may improve long-term maintenance of PA. PMID- 26137925 TI - Differentiating between copy-number-variation and gain-of-function mutation. PMID- 26137924 TI - Age-dependent levels of 5-methyl-, 5-hydroxymethyl-, and 5-formylcytosine in human and mouse brain tissues. AB - The absolute levels of 5-hydroxymethylcytosine (hmC) and 5-methylcytosine (mC) in human brain tissues at various ages were determined. Additionally, absolute levels of 5-formylcytosine (fC) in adult individuals and cytosine modification levels in sorted neurons were quantified. These data were compared with age related fC, hmC, and mC levels in mouse brain samples. For hmC, an initial steady increase is observed, which levels off with age to a final steady-state value of 1.2 % in human brain tissue. This level is nearly twice as high as in mouse cerebral cortex. In contrast, fC declines rapidly with age during early developmental stages, thus suggesting that while hmC is a stable epigenetic mark, fC is more likely an intermediate of active DNA demethylation during early brain development. The trends in global cytosine modification dynamics during the lifespan of an organism are conserved between humans and mice and show similar patterns in different organs. PMID- 26137926 TI - Catalytic Asymmetric Bromination of Unfunctionalized Olefins with H2O as a Nucleophile. AB - The dimeric cinchona alkaloid (DHQD)2 PHAL is used to catalyze an effective asymmetric bromohydroxylation of unfunctionalized olefins with H2 O as nucleophile an N-bromobenzamide as a bromine source. A variety of optically active bromohydrins are formed with up to 88 % ee. PMID- 26137927 TI - Oxidized tyrosinase: A possible antigenic stimulus for non-segmental vitiligo autoantibodies. AB - BACKGROUND: Vitiligo is a common pigmentary disorder, the precise etiology of which remains obscure. Tyrosinase, a key enzyme involved in melanin synthesis, has now been implicated as an autoantigen for vitiligo patients, but it is not clear how this prevalent protein becomes antigenic in vitiligo. OBJECTIVE: To investigate the status and contribution of oxidized tyrosinase in vitiligo and to explore whether oxidized tyrosinase has a role in disease progression. METHODS: Tyrosinase was modified by reactive-oxygen-species (ROS). Binding characteristics of antibodies in vitiligo patients (n=25) with varying disease duration (DD) and disease severity were screened against ROS-modified tyrosinase (ROS-tyrosinase) by immunoassays and their results were compared with healthy controls (n=23). RESULTS: The ROS caused extensive alterations in conformation and function of tyrosinase. Protein-A purified IgGs from vitiligo patients (Vt-IgG) showed strong binding to ROS-tyrosinase in comparison with IgGs from healthy controls (p<0.001). Interestingly, not only was there an increased number of subjects positive for anti-ROS-tyrosinase-IgGs, but also the levels of these IgGs were significantly higher among vitiligo patients, whose DD were >=10 years as compared to patients with short DD (<10 years). In addition, a significant correlation was observed between the levels of anti-ROS-tyrosinase-IgGs and the patients' ages or with disease severity. Experimentally induced anti-ROS tyrosinase-IgGs show reactivity with tyrosinase from vitiligo patients. Furthermore, vitiligo patients had lower levels of tyrosinase activity compared with healthy controls. Not only these, levels of carbonylation were also higher among vitiligo patients whose DD were >=10 years as compared to patients with DD<10 years. CONCLUSIONS: This is the first study to demonstrate the role of oxidized tyrosinase in vitiligo. Our novel results support an association between oxidized tyrosinase and vitiligo autoimmunity. The stronger antibodies response to oxidized tyrosinase in vitiligo patients with higher DD or with severe patients suggests that oxidized tyrosinase may be a useful biomarker in evaluating the progression of vitiligo and in elucidating the mechanisms of disease pathogenesis. PMID- 26137928 TI - Inclusion of 'ICU-Day' in a Logistic Scoring System Improves Mortality Prediction in Cardiac Surgery. AB - BACKGROUND Prolonged intensive care unit (ICU) stay is a predictor of mortality. The length of ICU stay has never been considered as a variable in an additive scoring system. How could this variable be integrated into a scoring system? Does this integration improve mortality prediction? MATERIAL AND METHODS The 'modified CArdiac SUrgery Score' (CASUS) was generated by implementing the length of stay as a new variable to the 'additive CASUS'. The 'logistic CASUS' already considers this variable. We defined outcome as ICU mortality and statistically compared the three CASUS models. Discrimination, comparison of receiver operating characteristic curves (DeLong's method), and calibration (observed/expected ratio) were analyzed on days 1-13. RESULTS Between 2007 and 2010, we included 5207 cardiac surgery patients in this prospective study. The mean age was 67.2 +/ 10.9 years. The mean length of ICU stay was 4.6 +/- 7.0 days and ICU mortality was 5.9%. All scores had good discrimination, with a mean area under the curve of 0.883 for the additive and modified, and 0.895 for the 'logistic CASUS'. DeLong analysis showed superiority in favor of the logistic model as from day 5. The calibration of the logistic model was good. We identified overestimation (days 1 5) and accurate (days 6-9) calibration for the additive and 'modified CASUS'. The 'modified CASUS' remained accurate but the 'additive CASUS' tended to underestimate the risk of mortality (days 10-13). CONCLUSIONS The integration of length of ICU stay as a variable improves mortality prediction significantly. An 'ICU-day' variable should be included into a logistic but not an additive model. PMID- 26137929 TI - [Proximal Femoral Osteotomies with the Paediatric Hip Plate (LCP): Valgus osteotomy]. AB - OBJECTIVE: Proximal femoral osteotomy with stable fixation and sufficient correction. Low complication rates due to exact preoperative planning. INDICATIONS: Congenital or traumatic femoral neck pseudarthrosis. Coxa vara. CONTRAINDICATIONS: None. In severe deformities, a single femoral osteotomy may not solve the problem; thus, additional correction, e.g., a pelvic osteotomy, is required. SURGICAL TECHNIQUE: Correct planning of the correction angle. Lateral approach. Subperiosteal detachment of vastus lateralis muscle. Place guide wire on the femoral neck to judge anteversion. Insert positioning wire 5 mm distal to trochanteric physis. Insert 2.8 mm Kirschner wire in the femoral neck. Osteotomy of the femur after marking the rotation by Kirschner wires or oscillating saw. Slide LC plate over Kirschner wires. Replace Kirschner wires with screws. Reduction of the femoral shaft to the plate with bone forceps. Definitive fixation of the plate to the femoral shaft by cortex or locking screws. Readaptation of vastus lateralis muscle over the plate. POSTOPERATIVE MANAGEMENT: Partial weightbearing for 4-6 weeks depending on the age of the patient without any external fixation (e. g. cast) is possible. RESULTS: Recent studies support the authors' findings of sufficient correction and stable fixation after proximal femoral osteotomy with the LCP pediatric hip plate. Low complication rates and stable fixation. PMID- 26137930 TI - [Treatment of posttraumatic cubitus varus in children and adolescents. Supracondylar humeral osteotomy using radial external fixation]. AB - OBJECTIVE: Precise adaptable fixation of a supracondylar humerus osteotomy with a radial/lateral external fixator to correct posttraumatic cubitus varus. INDICATIONS: Acquired, posttraumatic cubitus varus as a result of a malhealed and unsatisfactorily treated supracondylar humerus fracture. Idiopathic, congenital cubitus varus (very seldom) if the child (independent of age and after complete healing) is cosmetically impaired; stability of the elbow is reduced due to malalignment (hyperextension); secondary problems and pain (e. g., irritation of the ulnar nerve) are expected or already exist; or there is an explicit wish of the child/parents (relative indication). CONTRAINDICATIONS: In principle there are no contraindications provided that the indication criteria are filled. The common argument of age does not represent a contraindication in our opinion, since angular remodeling at the distal end of the humerus is practically nonexistent. SURGICAL TECHNIQUE: Basically, the surgical technique of the radial external fixator is used as previously described for stabilization of complex supracondylar humeral fractures. With the patient in supine position, the arm is placed freely on an arm table. Using a 4-5 cm long skin incision along the radial, supracondylar, the extracapsular part of the distal humerus is prepared, whereby great caution regarding the radial nerve is advised. In contrast to the procedure used in radial external fixation for supracondylar humeral fracture treatment, two Schanz screws are always fixed in each fragment at a distance of 1.5-2 cm. The osteotomy must allow the fragment to freely move in all directions. The proximal and distal two Schanz screws are then connected with short 4 mm carbon or stainless steel rods. These two rods are connected with each other over another rod using the tub-to-tub technique. Now the preliminary correction according the clinical situation can be performed and the clamps are tightened. Anatomical axis and function are checked. If these are radiologically and clinically perfect, all clamps are definitively tightened; if the alignment or the function is not perfect, then further adjustments can be made. POSTOPERATIVE MANAGEMENT: Due to the excellent stability, further immobilization not necessary. Immediate functional follow-up treatment performed according to pain. RESULTS: Adequate healing is usually expected within 6 weeks. At this time the external fixator can be removed in the fracture clinic. Because the whole operation is performed in an extraarticular manner and the mobility of the elbow is not affected, deterioration of function has never been observed. Also regarding the cosmetic/anatomical situation, good results are expected because they were already achieved intraoperatively. PMID- 26137931 TI - Caldariomyces fumago DSM1256 Contains Two Chloroperoxidase Genes, Both Encoding Secreted and Active Enzymes. AB - Inspection of transcriptome data from the chloroperoxidase (CPO)-producing fungus Caldariomyces fumago DSM1256 led to the discovery of two distinct CPO mRNA sequences. This strain could be shown to contain the newly identified isogene as well as produce and secrete both isoenzymes. The CPO2 enzyme bears high sequence similarity to the well-characterized CPO (87% identity for the mature proteins). It shows two insertions in the signal peptide and in the C-terminal propeptide, and one deletion in the mature polypeptide close to the C-terminus. Furthermore, it lacks one of the serine residues known to be O-glycosylated in the CPO sequence. The demonstration of a CPO isogene which is expressed as a secreted and active CPO clarifies the nature of this isoenzyme already identified in earlier reports. A structure model comparison shows a high conservation of the active site and the substrate channel, suggesting very similar catalytic properties. PMID- 26137932 TI - What are the core predictors of 'hassles' among patients with multimorbidity in primary care? A cross sectional study. AB - BACKGROUND: A limitation of service delivery in primary care in the United Kingdom is that services are often organised to manage discrete long-term conditions, using guidelines related to single conditions, and managed in clinics organised around single conditions. However, many older patients have more than one condition (so called multimorbidity). Qualitative research suggests that these patients experience 'hassles' in their care, including multiple appointments, poor co-ordination, and conflicting recommendations. However, there is limited quantitative evidence on the 'hassles' that patients with multimorbidity experience, or factors predicting 'hassles' in patients with multimorbidity. METHODS: We conducted a cross sectional study, mailing questionnaires to 1460 patients with multimorbidity identified from the disease registers of four general practices in the UK. Patients were asked to complete a range of self-report measures including measures of multimorbidity, measures of their experience of multimorbidity and service delivery. Data were analysed using regression modelling to assess the factors predicting 'hassles' in patients with multimorbidity. RESULTS: In total 33% (n = 486) of patients responded to the baseline survey. The 'hassles' most often reported by patients related to lack of information about conditions and treatment options, poor communication among health professionals, and poor access to specialist care. There was a significant relationship between numbers of conditions, and reports of 'hassles'. In multivariate analysis, 5 variables predicted more 'hassles': more long-term conditions, symptoms of anxiety and depression, younger age, being in paid employment, and not having a discussion with their GP in the last 12 months. CONCLUSION: Hassles are frequently reported by patients with multimorbidity in primary care. A priority for future research should be on the development of new models of care that better cater for these patients. This research highlights core hassles that need to be addressed, and the patient groups that are most at risk, which may aid in the design of these new models. PMID- 26137933 TI - Clinical Outcomes of Manual Aspiration Thrombectomy in Patients with Acute Myocardial Infarction: An Updated Meta-Analysis. AB - BACKGROUND: Recent trials on manual aspiration thrombectomy (AT) in patients with ST-elevation myocardial infarction did not show any significant benefits of AT. AIMS: The present meta-analysis was designed to systematically evaluate prospective randomized trials and assess the effects of AT on all-cause mortality, major cardiovascular events (MACE), target vessel revascularization, myocardial reinfarction, stroke and surrogate myocardial perfusion markers. METHODS AND RESULTS: We conducted an EMBASE and MEDLINE search for studies in which patients were randomized to treatment with AT plus primary percutaneous coronary intervention (PCI) versus PCI. We identified 16 prospective randomized trials which enrolled 10,437 controls that underwent conventional PCI and 10,385 patients who underwent PCI with AT with an average follow-up duration of 5.8 months. A significant reduction in MACE with AT was noted (OR 0.91; 95% CI 0.82 0.99; p = 0.04). In spite of improved TIMI 3 and myocardial blush grade 3 rates, AT did not significantly reduce all-cause mortality, target-vessel revascularization and myocardial infarction. Stroke rates were increased with AT. CONCLUSION: The results of this large meta-analysis of 20,822 patients suggest that adjunctive AT to PCI may be associated with improved myocardial reperfusion but limited benefits related to the clinical end-points. (c) 2015 S. Karger AG, Basel. PMID- 26137934 TI - Nanoshell-mediated targeted photothermal therapy of HER2 human breast cancer cells using pulsed and continuous wave lasers: an in vitro study. AB - In this study, we report the apoptosis induction in HER2 overexpressed breast cancer cells using pulsed, continuous wave lasers and polyvinylpyrrolidone (PVP) stabilized magneto-plasmonic nanoshells (PVP-MPNS) delivered by immunoliposomes. The immunoliposomes containing PVP-MPNS were fabricated and characterized. Heating efficiency of the synthesized nanostructures was calculated. The effect of functionalization on cellular uptake of nanoparticles was assessed using two cell lines of BT-474 and Calu-6. The best uptake result was achieved by functionalized liposome (MPNS-LAb) and BT-474. Also, the interaction of 514 nm argon (Ar) and Nd/YAG second harmonic 532-nm lasers with nanoparticles was investigated based on the temperature rise of the nanoshell suspension and the release value of 5(6)-carboxyfluorescein (CF) from CF/MPNS-loaded liposomes. The temperature increase of the suspensions after ten consecutive pulses of 532 nm and 5 min of irradiation by Ar laser were measured approximately 2 and 12 degrees C, respectively. The irradiation of CF/MPNS-loaded liposomes by Ar laser for 3 min resulted in 24.3 % release of CF, and in the case of 532 nm laser, the release was laser energy dependent. Furthermore, the comparison of CF release showed a higher efficiency for the Ar laser than by direct heating of nanoshell suspension using circulating water. The percentage of cell apoptosis after irradiation by Ar and 532 nm lasers were 44.6 and 42.6 %, respectively. The obtained results suggest that controlling the NP-laser interaction using optical properties of nanoshells and the laser parameters can be used to develop a new cancer therapy modality via targeted nanoshell and drug delivery. PMID- 26137935 TI - Highly Efficient and Low Turn-On Voltage Quantum Dot Light-Emitting Diodes by Using a Stepwise Hole-Transport Layer. AB - Highly efficient red quantum dot light-emitting diodes (QD-LEDs) with a very high current efficiency of 16 cd/A were demonstrated by adopting stepwise hole transport layers (HTLs) consisting of 4,4'-N,N'-dicarbazole-biphenyl (CBP) combined with N,N'-dicarbazolyl-3,5-benzene (mCP). The mCP layer plays two important roles in this kind of QD-LEDs. One is that it can block the electron to leak into the HTL due to its higher LUMO (LUMO = the lowest unoccupied molecular orbital) energy level than that of CBP; and the other is it can separate the carrier accumulation zone from the exciton formation interface, which is attributed to the stepwise hole-transport layer structure. Moreover, the lower HOMO (HOMO = the highest occupied molecular orbital) energy level of mCP decreases the hole-injection barrier from the HTL to the QD emitting layer, which improves the charge carrier balance injected into the QD layer, reducing the turn on voltage of QD-LEDs fabricated with the stepwise HTL structure. PMID- 26137936 TI - How Cell Concentrations Are Implicated in Cell Selectivity of Antimicrobial Peptides. AB - Antimicrobial peptides (AMPs) are known to selectively bind to and kill microbes over host cells. Contrary to a conventional view, there is now evidence that AMP's cell selectivity varies with cell densities and is not uniquely determined. Using a coarse-grained model, we study how the cell selectivity of membrane-lytic AMPs, defined as the ratio between their minimum hemolytic (MHC) and minimum inhibitory concentrations (MIC), depends on cell densities or on the way it is measured. A general picture emerging from our study is that the selectivity better captures peptide's intrinsic properties at low cell densities. The selectivity, however, decreases and becomes less intrinsic as the cell density increases, as long as it is chosen to be the same for both types of cells. Importantly, our results show that the selectivity can be excessively overestimated if higher host cell concentrations are used; in contrast, it becomes mistakenly small if measured for a mixture of both types of cells, even with similar choices of cell densities (i.e., higher host cell densities). Our approach can be used as a fitting model for relating the intrinsic selectivity to the apparent (cell-density-dependent) one. PMID- 26137937 TI - Intrinsic fluorescence-based at situ soft sensor for monitoring monoclonal antibody aggregation. AB - Intrinsic fluorescence spectroscopy, in conjunction with partial least squares regression (PLSR), was investigated as a potential technique for online quality control and quantitative monitoring of Immunoglobulin G (IgG) aggregation that occurs following exposure to conditions that emulate those that can occur during protein downstream processing. Initially, the impact of three stress factors (temperature, pH, and protein concentration) on the degree of aggregation determined using size exclusion chromatography data, was investigated by performing a central composite designexperiment and applying a fitting response surface model. This investigation identified the influence of the factors as well as the operating regions with minimum propensity to induce protein aggregation. Spectral changes pertinent to the stressed samples were also investigated and found to corroborate the high sensitivity of the intrinsic fluorescence to conformational changes of the proteins under study. Ultimately, partial least squares regression was implemented to formulate two fluorescence-based soft sensors for quality control--product classification--and quantitative monitoring- concentration of monomer. The resulting regression models exhibited accurate prediction ability and good potential for in situ monitoring of monoclonal antibody downstream purification processes. PMID- 26137938 TI - Echinococcus multilocularis in Kyrgyzstan: similarity in the Asian EmsB genotypic profiles from village populations of Eastern mole voles (Ellobius tancrei) and dogs in the Alay valley. AB - Echinococcus multilocularis is a cestode that causes human alveolar echinococcosis, a lethal zoonosis of public health concern in central Asia and western China. In the present study, one of 42 Eastern mole voles (Ellobius tancrei) caught in Sary Mogol (Alay valley, southern Kyrgyzstan) presented liver lesions with E. multilocularis from which the EmsB target was amplified. The Asian profile obtained was almost identical to one amplified from domestic dog faeces collected in a nearby village. This observation adds additional information to the potential role of E. tancrei in the transmission of E. multilocularis, and to the known distribution range of E. multilocularis (Asian strain) in central Asia. PMID- 26137939 TI - A histopathological analysis of the epidemiology of coronary atherosclerosis: an autopsy study. AB - BACKGROUND: Atherosclerosis accounts for a large proportion of cardiovascular system associated morbidity and mortality. We studied the possible association between the histopathological changes of the coronary atherosclerotic lesions and the risk of sudden cardiac death (SCD) using autopsy cases. METHODS: We performed an autopsy analysis (n = 13, 4 women, 9 men mean age 67.5 years; age range 56-93 years) of SCD which occurred in patients aged over 50 years during March 2010 to December 2013. The following variables were considered: sex, age, medical history, autopsy findings to macroscopic and histological evaluation of the heart. The autopsies were performed according to standard techniques. In all subjects, the heart was dissected following standard autopsy protocol and a 5 cm section of the right coronary artery (RCA) in the atrio-ventricular groove from its origin, a 5 cm segment of the left anterior descending artery (LADA) distal to the origin of the circumflex artery, but including the region of origin of the circumflex branch and left coronary artery (LCA) from its origin till the circumflex branch were excised, dissected out, fixed in 10% formalin, marked for identification and sent for histopathological analysis. RESULTS: Atherosclerotic plaques were identified in 6.5% of specimens, 69.34% of males and 30.66% of female. Such plaques were typically concentric and more represented with necrosis, calcification, cholesterol crystals, and giant cells, as well as had a higher inflammatory cell count. Furthermore, intima and media thickness of coronary arteries were significantly higher in studied specimens with visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the periadventitial tissue. Furthermore, the degree of microscopic lesion of atherosclerosis increased proportionally with the increase in the intensity of lipid deposition and with the percentage of collagen in the atherosclerotic plaques. CONCLUSION: In this study, age estimate to be a risk factor for coronary atherosclerosis in individuals more than 50 years old and may be used to predict SCD. Altogether, an enhanced understanding of the pathobiologic processes responsible for atherosclerotic changes might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes. PMID- 26137940 TI - Two-year assessment of the efficacy and safety of sitagliptin in elderly patients with type 2 diabetes: Post hoc analysis of the ASSET-K study. AB - BACKGROUND: There have only been a few reports about use of dipeptidyl peptidase 4 (DPP-4) inhibitors in elderly patients with type 2 diabetes mellitus (T2DM), suggesting that the safety of these agents has not been sufficiently demonstrated. We performed a comparative review of the efficacy and safety of sitagliptin for Japanese patients with T2DM managed in the real-world clinical setting. METHODS: An age-stratified analysis was performed of 831 patients who were treated with sitagliptin for 2 years. Parameters assessed included the hemoglobin A1c (HbA1c), body weight, serum creatinine, and adverse events. HbA1c and the incidence of hypoglycemia were also evaluated in patients treated with sitagliptin and a sulfonylurea (SU), who were divided into three age groups (<65 years, 65-74 years, and >=75 years). RESULTS: Comparison of glycemic control parameters, laboratory values, and adverse events revealed significant improvement of HbA1c, casual postprandial plasma glucose, and fasting plasma glucose in each age group with no change in body weight. Serum creatinine increased significantly in all age groups. Hypoglycemia only occurred in patients who received combined treatment with an SU and sitagliptin, and there was no age related difference in its incidence. CONCLUSIONS: HbA1c was improved by 2 years of sitagliptin therapy in all three age groups, and age did not seem to influence the incidence of hypoglycemic events. These results confirm the efficacy and safety of sitagliptin in patients >= 75 years old, suggesting that it is also useful for treating elderly patients with T2DM. PMID- 26137942 TI - Probable Interaction Between Warfarin and Banana Flakes Supplement. AB - PURPOSE: To describe a case of subtherapeutic international normalized ratio (INR) associated with concomitant use of warfarin and banana flakes in a patient with diarrhea. SUMMARY: A man in his 30s was hospitalized for an elective procedure, but his stay was complicated by cerebral venous thrombosis requiring intravenous infusion of unfractionated heparin, ventilator-associated pneumonia, bacteremia requiring broad-spectrum antimicrobials and percutaneous endoscopic gastrostomy tube placement, and diarrhea. Eventually, the heparin was transitioned to warfarin. After several days of therapeutic INR, the INR became subtherapeutic and remained so for 3 days. The decreased INR correlated temporally with initiation of consistent administration of dried banana flakes to treat diarrhea and the subsequent decrease in the rate and extent of diarrhea. Diarrhea decreases the amount and activity of vitamin K-producing intestinal flora and dietary vitamin K absorption, resulting in increased INR. Resolution of diarrhea secondary to banana flakes administration in this patient may have contributed to the decreased INR by causing a relative increase in vitamin K producing flora and vitamin K absorption. A probability score of 5 was obtained upon applying the Drug Interaction Probability Scale modified to address interactions between warfarin and dietary supplements, indicating a probable interaction between warfarin and banana flakes. CONCLUSION: Concomitant use of warfarin and banana flakes supplements may result in a reduced rate and extent of diarrhea and may be associated with subtherapeutic INR and decreased warfarin efficacy. Practitioners must be aware of this potential interaction and closely monitor INR and adjust warfarin doses accordingly. PMID- 26137941 TI - Lamina propria macrophage phenotypes in relation to Escherichia coli in Crohn's disease. AB - BACKGROUND: Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn's disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage. METHODS: Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR. RESULTS: E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFalpha, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFalpha, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls. CONCLUSION: In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation. PMID- 26137943 TI - Depression Management by NICU Nurses: Mothers' Views. AB - The purpose of this article was to evaluate attitudes of mothers of newborns hospitalized on the neonatal intensive care unit (NICU) toward nurse-delivered depression screening and counseling. NICU mothers (N = 200) completed questionnaires assessing their views toward being screened for depression by nurses, treatment provider preference, and interest in learning about Listening Visits (LV), a nurse-delivered intervention. The views of 23 LV recipients were also assessed. Most mothers were receptive to depression screening by nurses, two thirds would see a nurse for counseling, and half were interested in learning more about LV. Among LV recipients, half readily embraced the idea and the remaining recipients were skeptical but opted to try. After receiving LV, recipients unanimously rated LV and the skill of the LV provider highly. Screening and counseling by NICU nurses could increase detection of depression and treatment use among at-risk women. Assessing nurses' perspectives about implementing this model of care is an important future research direction. PMID- 26137944 TI - Genomics of American Black Bears Reveal Surprising Ancient Migration Patterns to Aid Conservation Efforts. PMID- 26137945 TI - Cost and cost-effectiveness of soil-transmitted helminth treatment programmes: systematic review and research needs. AB - BACKGROUND: In this time of rapidly expanding mass drug administration (MDA) coverage and the new commitments for soil-transmitted helminth (STH) control, it is essential that resources are allocated in an efficient manner to have the greatest impact. However, many questions remain regarding how best to deliver STH treatment programmes; these include which age-groups should be targeted and how often. To perform further analyses to investigate what the most cost-effective control strategies are in different settings, accurate cost data for targeting different age groups at different treatment frequencies (in a range of settings) are essential. METHODS: Using the electronic databases PubMed, MEDLINE, and ISI Web of Knowledge, we perform a systematic review of costing studies and cost effectiveness evaluations for potential STH treatment strategies. We use this review to highlight research gaps and outline the key future research needs. RESULTS: We identified 29 studies reporting costs of STH treatment and 17 studies that investigated its cost-effectiveness. The majority of these pertained to programmes only targeting school-aged children (SAC), with relatively few studies investigating alternative preventive chemotherapy (PCT) treatment strategies. The methods of cost data collection, analysis and reporting were highly variable among the different studies. Only four of the costing studies were found to have high applicability for use in forthcoming economic evaluations. There are also very few studies quantifying the costs of increasing the treatment frequency. CONCLUSIONS: The absence of cost data and inconsistencies in the collection and analysis methods constitutes a major research gap for STH control. Detailed and accurate costs of targeting different age groups or increasing treatment frequency will be essential to formulate cost-effective public health policy. Defining the most cost-effective control strategies in different settings is of high significance during this period of expanding MDA coverage and new resource commitments for STH control. PMID- 26137951 TI - Racial Disparity in Cognitive and Functional Disability in Hypertension and All Cause Mortality. AB - BACKGROUND: Subjective cognitive and functional limitations are early markers of future dementia and physical disability. Hypertension may increase the risk of dementia; however, the magnitude and significance of subjective limitations in the hypertensive US population are unknown, particularly in African Americans who bear the greatest burden of hypertension. Our objectives were to assess the prevalence and racial disparity of subjective cognitive and functional limitations and their impact on mortality in the hypertensive US population. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2010 (N = 28,477; 31% with hypertension; 11% African American), which included blood pressure measurement, self-reported cognitive and functional (physical and non-physical) limitations, and all-cause mortality. Complex survey regression models were used. RESULTS: In the United States, 8% of the hypertensive population reported cognitive and 25% reported functional limitations (vs. 5.7% and 15% respectively in the non hypertensive population, P < 0.0001). Hypertensive African Americans carried the highest burden of cognitive (11%, P = 0.01) and functional (27%, P = 0.03) limitations compared to non-hypertensive African Americans and to non-African Americans. All-cause mortality was significantly higher in hypertensive individuals who reported cognitive or functional limitations (P < 0.0001 for both) relative to those without either. CONCLUSIONS: The prevalence of cognitive and functional disability is larger in the US hypertensive population compared to the non-hypertensive population. African Americans with hypertension carry a disproportionate burden of these limitations. Individuals with hypertension who report cognitive or functional symptoms have higher all-cause mortality and query about these symptoms should be part of hypertension evaluation. PMID- 26137952 TI - Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women's Health Initiative Memory Study. AB - BACKGROUND: To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. METHODS: Prospective follow-up of 6,426 cognitively intact women aged 65-79 years enrolled in the Women's Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP >= 140 mm Hg or diastolic BP >= 90 mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). RESULTS: Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP >=140/90 mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500 mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). CONCLUSIONS: Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056. PMID- 26137953 TI - Patient-Level Discordance in Population Percentiles of the Total Cholesterol to High-Density Lipoprotein Cholesterol Ratio in Comparison With Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol: The Very Large Database of Lipids Study (VLDL-2B). AB - BACKGROUND: The total cholesterol to high-density lipoprotein cholesterol (TC/HDL C) ratio, estimated low-density lipoprotein cholesterol (LDL-C), and non-HDL-C are routinely available from the standard lipid profile. We aimed to assess the extent of patient-level discordance of TC/HDL-C with LDL-C and non-HDL-C, because discordance suggests the possibility of additional information. METHODS AND RESULTS: We compared population percentiles of TC/HDL-C, Friedewald-estimated LDL C, and non-HDL-C in 1 310 432 US adults from the Very Large Database of Lipids. Lipid testing was performed by ultracentrifugation (Vertical Auto Profile, Atherotech, AL). One in 3 patients had >=25 percentile units discordance between TC/HDL-C and LDL-C, whereas 1 in 4 had >=25 percentile units discordance between TC/HDL-C and non-HDL-C. The proportion of patients with TC/HDL-C > LDL-C by >=25 percentile units increased from 3% at triglycerides <100 mg/dL to 51% at triglycerides 200 to 399 mg/dL. On a smaller scale, TC/HDL-C > non-HDL-C discordance by >=25 percentile units increased from 6% to 21%. In those with <15th percentile levels of LDL-C (<70 mg/dL) or non-HDL-C (<93 mg/dL), a respective 58% and 46% were above the percentile-equivalent TC/HDL-C of 2.6. Age, sex, and directly measured components of the standard lipid profile explained >86% of the variance in percentile discordance between TC/HDL-C versus LDL-C and non-HDL-C. CONCLUSIONS: In this contemporary, cross-sectional, big data analysis of US adults who underwent advanced lipid testing, the extent of patient-level discordance suggests that TC/HDL-C may offer potential additional information to LDL-C and non-HDL-C. Future studies are required to determine the clinical implications of this observation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01698489. PMID- 26137954 TI - Microbleeds. PMID- 26137955 TI - Cerebral Microbleeds Are Associated With an Increased Risk of Stroke: The Rotterdam Study. AB - BACKGROUND: Cerebral microbleeds are highly prevalent in people with clinically manifest cerebrovascular disease and have been shown to increase the risk of stroke recurrence. Microbleeds are also frequently found in healthy elderly, a population in which the clinical implication of microbleeds is unknown. METHODS AND RESULTS: In the population-based Rotterdam Study, the presence, number, and location of microbleeds were assessed at baseline on brain MRI of 4759 participants aged >=45 years. Participants were followed for incident stroke throughout the study period (2005-2013). We used Cox proportional hazards to investigate if people with microbleeds were at increased risk of stroke in comparison with those without microbleeds, adjusting for demographic, genetic, and cardiovascular risk, and cerebrovascular imaging markers. Microbleed prevalence was 18.7% (median count 1 [1-111]). During mean follow-up of 4.9 years (standard deviation, 1.6) 93 strokes occurred (72 ischemic, 11 hemorrhagic, and 10 unspecified). Microbleed presence was associated with an increased risk of all strokes (hazard ratio, 1.93; 95% confidence interval, 1.25-2.99). The risk increased with greater microbleed count. In comparison with those without microbleeds, participants with microbleeds in locations suggestive of cerebral amyloid angiopathy (lobar with or without cerebellar microbleeds) were at increased risk of intracerebral hemorrhage (hazard ratio, 5.27; 95% confidence interval, 1.38-20.23). Microbleeds at other locations were associated with an increased risk of both ischemic stroke and intracerebral hemorrhage. CONCLUSIONS: Microbleeds on MRI are associated with an increased risk of stroke in the general population. Our results strengthen the notion that microbleeds mark progression of cerebrovascular pathology and represent a precursor of stroke. PMID- 26137956 TI - Effect of the myeloperoxidase inhibitor AZD3241 on microglia: a PET study in Parkinson's disease. AB - Impaired mitochondrial function, oxidative stress and formation of excessive levels of reactive oxygen species play a key role in neurodegeneration in Parkinson's disease. Myeloperoxidase is a reactive oxygen generating enzyme and is expressed by microglia. The novel compound AZD3241 is a selective and irreversible inhibitor of myeloperoxidase. The hypothesized mechanism of action of AZD3241 involves reduction of oxidative stress leading to reduction of sustained neuroinflammation. The purpose of this phase 2a randomized placebo controlled multicentre positron emission tomography study was to examine the effect of 8 weeks treatment with AZD3241 on microglia in patients with Parkinson's disease. Parkinson patients received either AZD3241 600 mg orally twice a day or placebo (in 3:1 ratio) for 8 weeks. The binding of (11)C-PBR28 to the microglia marker 18 kDa translocator protein, was examined using positron emission tomography at baseline, 4 weeks and 8 weeks. The outcome measure was the total distribution volume, estimated with the invasive Logan graphical analysis. The primary statistical analysis examined changes in total distribution volume after treatment with AZD3241 compared to baseline. Assessments of safety and tolerability of AZD3241 included records of adverse events, vital signs, electrocardiogram, and laboratory tests. The patients had a mean age of 62 (standard deviation = 6) years; 21 were male, three female and mean Unified Parkinson's Disease Rating Scale III score (motor examination) ranged between 6 and 29. In the AD3241 treatment group (n = 18) the total distribution volume of (11)C-PBR28 binding to translocator protein was significantly reduced compared to baseline both at 4 and 8 weeks (P < 0.05). The distribution volume reduction across nigrostriatal regions at 8 weeks ranged from 13-16%, with an effect size equal to 0.5-0.6. There was no overall change in total distribution volume in the placebo group (n = 6). AZD3241 was safe and well tolerated. The reduction of (11)C-PBR28 binding to translocator protein in the brain of patients with Parkinson's disease after treatment with AZD3241 supports the hypothesis that inhibition of myeloperoxidase has an effect on microglia. The results of the present study provide support for proof of mechanism of AZD3241 and warrant extended studies on the efficacy of AZD3241 in neurodegenerative disorders. PMID- 26137957 TI - Neural detection of complex sound sequences or of statistical regularities in the absence of consciousness? PMID- 26137958 TI - Reply: Neural detection of complex sound sequences or of statistical regularities in the absence of consciousness? PMID- 26137959 TI - CLIP-ASAP-HSQC for fast and accurate extraction of one-bond couplings from isotropic and partially aligned molecules. AB - Fast measurement of heteronuclear one-bond couplings, a class of NMR parameters valuable for structure elucidation, is highly desirable, especially if samples undergo chemical reactions or dynamic processes are observed. Methods presented so far face severe limitations in terms of resolution, accessible bandwidth, and sensitivity. We present the CLean InPhase-Acceleration by Sharing Adjacent Polarization-HSQC (CLIP-ASAP-HSQC) pulse sequence that allows fast acquisition of spectra with clean inphase multiplets in about 25 s. The performance in terms of accurate extraction of one-bond couplings is demonstrated on three test samples including partially aligned molecules. PMID- 26137960 TI - Hydroxyurea treatment does not increase blood viscosity and improves red blood cell rheology in sickle cell anemia. PMID- 26137962 TI - Extensive volatile loss during formation and differentiation of the Moon. AB - Low estimated lunar volatile contents, compared with Earth, are a fundamental observation for Earth-Moon system formation and lunar evolution. Here we present zinc isotope and abundance data for lunar crustal rocks to constrain the abundance of volatiles during the final stages of lunar differentiation. We find that ferroan anorthosites are isotopically heterogeneous, with some samples exhibiting high delta(66)Zn, along with alkali and magnesian suite samples. Since the plutonic samples were formed in the lunar crust, they were not subjected to degassing into vacuum. Instead, their compositions are consistent with enrichment of the silicate portions of the Moon in the heavier Zn isotopes. Because of the difference in delta(66)Zn between bulk silicate Earth and lunar basalts and crustal rocks, the volatile loss likely occurred in two stages: during the proto lunar disk stage, where a fraction of lunar volatiles accreted onto Earth, and from degassing of a differentiating lunar magma ocean, implying the possibility of isolated, volatile-rich regions in the Moon's interior. PMID- 26137961 TI - CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol. AB - DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8 year event free survival in this treatment protocol [70.2% +/- 1.2% for patients with deletions versus 83.5% +/- 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728. PMID- 26137963 TI - Unintended Consequences of the New National Kidney Allocation Policy in the United States. AB - The new national Kidney Allocation System of the Organ Procurement and Transplantation Network (OPTN), effective as of December 4, 2014, was designed to improve the chances of transplanting the most highly sensitized patients on the waitlist, those with calculated panel reactive antibody values of 98%, 99% and 100%. Recently, it was suggested that these highly sensitized patients will experience inequitable access, given the reported high prevalence of antibodies to HLA-DP, and the fact that only about 1/3 of deceased donors are typed for HLA DP antigens. Here we report that 320/2948 flow cytometric crossmatches performed for the Northwestern transplant program over the past 28 months were positive solely due to HLA-DP donor-specific antibodies (11%; 16.5% of patients with HLA antibodies-sensitized patients). We further show that 58/207 (12%) HLA-DR serologically matched donor-recipient pairs had a positive B cell flow crossmatch due to donor-specific HLA class II antibodies, and 2/34 (6%) serologic zero-HLA-A B-DR mismatch had a positive flow crossmatch due to HLA-DSA. We therefore provide information regarding the necessity and importance of complete donor HLA typing including both chains of the HLA-DP antigen (encoded by HLA-DPA1 and HLA-DPB1) at the time of organ offer. PMID- 26137964 TI - Oral health behaviors and bacterial transmission from mother to child: an explorative study. AB - BACKGROUND: Health behaviors play a major role in the prevention of the most common oral diseases. To investigate health behaviors related to the potential transmission of oral bacteria from mother to child using novel multiple correspondence analysis (MCA). METHODS: Mothers (n = 313) with children under three years attending two municipal child health clinics in Finland completed a self-administered questionnaire on health knowledge and behaviors such as sharing a spoon with their child, kissing on the lips, and the mothers' tooth brushing, smoking, age, and level of education. We used MCA to reveal the relationships between the mothers' behaviors and background factors, along with unconditional, binary, multivariable logistic regression models, odds ratios (OR) and their 95 % confidence intervals (95 %CI). RESULTS: Of the mothers, 38 % kissed their child on the lips and 14 % shared a spoon with their child; 11 % believed that oral bacteria cannot be transmitted from mother to child. Two-thirds (68 %) of them reported tooth brushing twice daily, and 80 % were non-smokers. MCA revealed two diverging dimensions of the mothers' behaviors: a 'horizontal' one showing clear evidence of relationships between tooth brushing, smoking, age and education, whereas the 'vertical' one revealed the mothers' habits of kissing the child on the lips and sharing a spoon related to each other. Spoon sharing was related to the kissing on lips (OR 10.3), a higher level of education (OR 3.1), and, inversely, older age (OR 0.1), whereas kissing on lips behavior was inversely related to a higher level of education (OR 0.5). CONCLUSION: The study revealed two diverging dimensions of the mothers' health behaviors. More emphasis in health education ought to be put to how to avoid bacterial transmission from caregiver to child during feeding. PMID- 26137965 TI - Massive Hepatomegaly With Respiratory Distress in a Newborn. PMID- 26137967 TI - Multivalent thioglycopeptoids via photoclick chemistry: potent affinities towards LecA and BC2L-A lectins. AB - Solution-phase synthesis of linear and cyclic beta- and alpha,beta-peptoids was coupled to photo-induced thiol-ene coupling reaction to readily access multivalent thioglycoclusters. A tetrameric cyclic beta-peptoid scaffold displaying 1-thio-beta-d-galactose or 1-thio-alpha-d-mannose has revealed by ITC experiments efficient binding potency for bacterial lectins LecA and BC2L-A, respectively. PMID- 26137968 TI - Laparoscopic right colectomy reduces short-term mortality and morbidity. Results of a systematic review and meta-analysis. AB - PURPOSE: While definitive long-term results are not yet available, the global safety and oncologic adequacy of laparoscopic surgery for right colectomy remain controversial. The aim of the study was to evaluate differences in safety of laparoscopic right colectomy, compared with open surgery, with particular attention to cancer patients. METHODS: A systematic review from 1991 to 2014 was performed searching the MEDLINE and EMBASE databases (PROSPERO Registration number: CRD42014015256). We included randomised and controlled clinical studies comparing laparoscopic and open resection for rectal cancer. Primary endpoints were 30 days mortality and overall morbidity. Then, a meta-analysis was conducted by a fixed-effect model, performing a sensitivity analysis by a random-effect model. Relative risk (RR) was used as an indicator of treatment effect; a RR less than 1.0 was in favour of laparoscopy. Publication bias was assessed by funnel plot, heterogeneity by the I (2) test and subgroup analysis on oncologic patients. RESULTS: Twenty-seven studies, representing 3049 patients, met the inclusion criteria; only 2 were randomised for a total of 211 patients. Mortality was observed in 1.2 % of patients in the laparoscopic group and in 3.4 % of patients in the open group. The overall RR was 0.45 (95 % CI 0.21-0.93, p = 0.031). The raw incidence of overall complications was significantly lower in the laparoscopic group (16.8 %) compared to the open group (24.2 %). The overall RR was 0.81 (95 % CI 0.70-0.95, p = 0.007). CONCLUSIONS: Based on the evidence of few randomised and mostly controlled series, mortality and morbidity were significantly lower after laparoscopy compared to open surgery. PMID- 26137966 TI - Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis. AB - BACKGROUND: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients. METHODS: Clinical pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model. RESULTS: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45). CONCLUSIONS: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases. PMID- 26137969 TI - Comparison of Bispectral Index and Entropy values with electroencephalogram during surgical anaesthesia with sevoflurane. AB - BACKGROUND: Concomitantly recorded Bispectral Index(r) (BIS) and EntropyTM values sometimes show discordant trends during general anaesthesia. Previously, no attempt had been made to discover which EEG characteristics cause discrepancies between BIS and Entropy. We compared BIS and Entropy values, and analysed the changes in the raw EEG signal during surgical anaesthesia with sevoflurane. METHODS: In this prospective, open-label study, 65 patients receiving general anaesthesia with sevoflurane were enrolled. BIS, Entropy and multichannel digital EEG were recorded. Concurrent BIS and State Entropy (SE) values were selected. Whenever BIS and SE values showed >=10-unit disagreement for >=60 s, the raw EEG signal was analysed both in time and frequency domain. RESULTS: A >=10-unit disagreement >=60 s was detected 428 times in 51 patients. These 428 episodes accounted for 5158 (11%) out of 45 918 analysed index pairs. During EEG burst suppression, SE was higher than BIS in 35 out of 49 episodes. During delta-theta dominance, BIS was higher than SE in 141 out of 157 episodes. During alpha or beta activity, SE was higher than BIS in all 49 episodes. During electrocautery, both BIS and SE changed, sometimes in the opposite direction, but returned to baseline values after electrocautery. Electromyography caused index disagreement four times (BIS > SE). CONCLUSIONS: Certain specific EEG patterns, and artifacts, are associated with discrepancies between BIS and SE. Time and frequency domain analyses of the original EEG improve the interpretation of studies involving BIS, Entropy and other EEG-based indices. CLINICAL TRIAL REGISTRATIONCLINICALTRIALSGOVIDENTIFIER: NCT01077674. PMID- 26137970 TI - Systematic review of empowerment measures in health promotion. AB - Empowerment, a multi-level construct comprising individual, community and organizational domains, is a fundamental value and goal in health promotion. While a range of scales have been developed for the measurement of empowerment, the qualities of these have not been rigorously assessed. The aim of this study was to evaluate the measurement properties of quantitative empowerment scales and their applicability in health promotion programs. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was done to evaluate empowerment scales across three dimensions: item development, reliability and validity. This was followed by assessment of measurement properties using a ratings scale with criteria addressing an a priori explicit theoretical framework, assessment of content validity, internal consistency and factor analysis to test structural validity. Of the 20 studies included in this review, only 8 (40%) used literature reviews, expert panels and empirical studies to develop scale items and 9 (45%) of studies fulfilled >=5 criteria on the ratings scale. Two studies (10%) measured community empowerment and one study measured organizational empowerment, the rest (85%) measured individual empowerment. This review highlights important gaps in the measurement of community and organizational domains of empowerment using quantitative scales. A priority for future empowerment research is to investigate and explore approaches such as mixed methods to enable adequate measurement of empowerment across all three domains. This would help health promotion practitioners to effectively measure empowerment as a driver of change and an outcome in health promotion programs. PMID- 26137971 TI - Vaginal colonisation by probiotic lactobacilli and clinical outcome in women conventionally treated for bacterial vaginosis and yeast infection. AB - BACKGROUND: The aim of this study was to investigate the colonisation by lactobacilli and clinical outcome in women with bacterial vaginosis (BV) and recurrent vulvovaginal candidiasis (R-VVC) receiving antibiotic or anti-fungal treatment in combination with the probiotic EcoVag(r) capsules. METHODS: A total of 40 Scandinavian women diagnosed with BV or VVC on the basis of Amsel's criteria or clinical symptoms were consecutively recruited in two pilot open label clinical trials. In trial I, women with BV were treated with clindamycin and metronidazole followed by vaginal EcoVag(r) capsules, containing Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869, for 5 consecutive days after each antibiotic treatment. In trial II, women were recruited in three groups as follows: women with BV receiving clindamycin and metronidazole treatment together with a prolonged administration of EcoVag(r) (10 consecutive days after each antibiotic treatment followed by weekly administration of capsules for next four months), women with R-VVC receiving extended fluconazole and EcoVag(r) treatment, and women receiving extended fluconazole treatments only. The difference in frequency of isolation of EcoVag(r) strains or other lactobacilli between groups was compared by Fisher's exact test. RESULTS: The 6-month cure rate for BV was 50 % in trial I while both the 6- and 12-month cure rates were 67 % in trial II. The 6- and 12-month cure rates for VVC were 100 % and 89 % in women receiving fluconazole and EcoVag(r), and 100 % and 70 % in women receiving fluconazole only. The frequency of isolation of any Lactobacillus species during the course of the study was associated with cure of BV in trial I and II, whereas the frequency of isolation of EcoVag(r) strains was significantly associated with the cure of BV in trial II only. As previously observed, a change in sexual partner was associated with relapse of BV with an Odds ratio of 77 (95 % CI: 2.665 to 2225). CONCLUSIONS: The study suggests that the treatment with antibiotics or anti-fungal medication in combination with EcoVag(r) capsules provide long-term cure against BV and R-VVC as compared to previous reports. TRIAL REGISTRATION: ClinicalTrials.gov NCT02295579 . Registered November 20, 2014. PMID- 26137972 TI - The clinical relevance of animal models in Sjogren's syndrome: the interferon signature from mouse to man. AB - Mouse models have been widely used to elucidate the pathogenic mechanisms of human diseases. The advantages of using these models include the ability to study different stages of the disease with particular respect to specific target organs, to focus on the role of specific pathogenic factors and to investigate the effect of possible therapeutic interventions. Sjogren's syndrome (SS) is a systemic autoimmune disease, characterised by lymphocytic infiltrates in the salivary and lacrimal glands. To date, effective therapy is not available and treatment has been mainly symptomatic. Ongoing studies in murine models are aimed at developing more effective and targeted therapies in SS. The heterogeneity of SS will most probably benefit from optimising therapies, tailored to specific subgroups of the disease. In this review, we provide our perspective on the importance of subdividing SS patients according to their interferon signature, and recommend choosing appropriate mouse models for interferon-positive and interferon-negative SS subtypes. Murine models better resembling human-disease phenotypes will be essential in this endeavour. PMID- 26137973 TI - Neural correlates of masked and unmasked face emotion processing in youth with severe mood dysregulation. AB - Reproducibility of results is important in improving the robustness of conclusions drawn from research, particularly in functional magnetic resonance imaging (fMRI). In this study, we aim to replicate a previous study on the neural correlates of face emotion processing above and below awareness level using an independent sample of youth with severe mood dysregulation (SMD) and healthy volunteers (HV). We collected fMRI data in 17 SMD and 20 HV, using an affective priming paradigm with masked (17 ms) and unmasked (187 ms) faces (angry, happy, neutral, blank oval). When processing masked and unmasked angry faces, SMD patients exhibited increased activation in the parahippocampal gyrus (PHG) and superior temporal gyrus relative to HV. When processing masked and unmasked happy faces, SMD patients showed decreased activation in the insula, PHG and thalamus compared with HV. During masked face processing in general across emotions, youth with SMD showed greater ventromedial prefrontal cortex (vmPFC) activation relative to HV. Perturbed activation in emotion processing areas (e.g. insula, PHG, superior temporal gyrus and thalamus) manifests as hyper-sensitivity toward negative emotions and hypo-sensitivity toward positive emotions may be important in the etiology and maintenance of irritability, aggression and depressive symptoms in SMD. vmPFC dysfunction may mediate over-reactivity to face emotions associated with irritability. PMID- 26137974 TI - Face processing among twins with and without autism: social correlates and twin concordance. AB - Autism spectrum disorder (ASD) has a strong heritable basis, as evidenced by twin concordance rates. Within ASD, symptom domains may arise via independent genetic contributions, with varying heritabilities and genetic mechanisms. In this article, we explore social functioning in the form of (i) electrophysiological and behavioral measures of face processing (P1 and N170) and (ii) social behavior among child and adolescent twins with (N = 52) and without ASD (N = 66). Twins without ASD had better holistic face processing and face memory, faster P1 responses and greater sensitivity to the effects of facial inversion on P1. In contrast, N170 responses to faces were similar across diagnosis, with more negative amplitudes for faces vs non-face images. Across the sample, stronger social skills and fewer social difficulties were associated with faster P1 and N170 responses to upright faces, and better face memory. Twins were highly correlated within pairs across most measures, but correlations were significantly stronger for monozygotic vs dizygotic pairs on N170 latency and social problems. We suggest common developmental influences across twins for face processing and social behavior, but highlight (i) neural speed of face processing and (ii) social difficulties as important avenues in the search for genetic underpinnings in ASD. PMID- 26137975 TI - Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial. AB - OBJECTIVE: To explore the safety and tolerability of atacicept in combination with rituximab in patients with active rheumatoid arthritis (RA) receiving rituximab re-treatment. METHODS: In this randomized, double-blind, placebo controlled pilot trial, 2 infusions (1,000 mg per infusion) of intravenous rituximab, given 2 weeks apart, were followed by once-weekly subcutaneous injections of 150 mg atacicept or placebo for 25 weeks. Primary end points were the nature, incidence, and severity of adverse events (AEs). Secondary end points were the effects on peripheral blood B cells, disease activity biomarkers, and American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) response rates. RESULTS: Eighteen patients were randomized to receive atacicept and 9 to receive placebo. AEs occurred in 17 atacicept-treated patients (94.4%) and in all 9 placebo-treated patients (100%). There were no infection-related serious adverse events. Hypersensitivity and injection site reactions were more common, and more patients withdrew due to AEs, in the atacicept group. Median reductions in Ig levels from baseline to week 32 were greater with atacicept (median change in IgG -31.2%, IgM -60.9%, and IgA -56.4%) than with placebo (median change in IgG -4.4%, IgM -15.9%, and IgA -8.2%). Peripheral B cell numbers remained low in all patients after rituximab-mediated B cell depletion, limiting comparison of time to recovery between treatment groups. There were no between-group differences in ACR20, ACR50, and ACR70 response rates. CONCLUSION: In this exploratory trial, atacicept in combination with rituximab showed no new safety issues. Peripheral B cell counts remained too low to determine whether atacicept delayed B cell re-expansion following rituximab-mediated depletion. Despite clear biologic effects, adding atacicept to rituximab in patients with active RA was not associated with clinical benefit. PMID- 26137976 TI - Increased reservoir ages and poorly ventilated deep waters inferred in the glacial Eastern Equatorial Pacific. AB - Consistent evidence for a poorly ventilated deep Pacific Ocean that could have released its radiocarbon-depleted carbon stock to the atmosphere during the last deglaciation has long been sought. Such evidence remains lacking, in part due to a paucity of surface reservoir age reconstructions required for accurate deep ocean ventilation age estimates. Here we combine new radiocarbon data from the Eastern Equatorial Pacific (EEP) with chronostratigraphic calendar age constraints to estimate shallow sub-surface reservoir age variability, and thus provide estimates of deep-ocean ventilation ages. Both shallow- and deep-water ventilation ages drop across the last deglaciation, consistent with similar reconstructions from the South Pacific and Southern Ocean. The observed regional fingerprint linking the Southern Ocean and the EEP is consistent with a dominant southern source for EEP thermocline waters and suggests relatively invariant ocean interior transport pathways but significantly reduced air-sea gas exchange in the glacial southern high latitudes. PMID- 26137977 TI - Sexual Activity and Condom Use among Israeli Adolescents. AB - INTRODUCTION: In Israel, as in other industrialized countries, the age of sexual debut among adolescents has declined, and the rate of sexually transmitted infections (STI) has risen, but the motivations and attitudes of Israeli adolescents toward carrying condoms have yet to be studied. AIMS: The aims of this study were to establish the associations (if any) between demographic characteristics and the knowledge held by Jewish Israeli adolescents about HIV transmission, their attitudes toward condom use and sexual experience, and to explore their recommendations to increase condom use. METHODS: The method used was an analysis of sexual experience and practices, attitudes toward condom carrying and condom use among a national representative sample of Jewish adolescents aged 15-18. MAIN OUTCOME MEASURES: Two dichotomized measures were assessed: (i) sexual experience (defined as having had previous consensual oral/vaginal/anal sex); and (ii) the practice of carrying a condom on a regular basis. RESULTS: Of all 410 participants, 14.6% carried condoms, 18.3% had sexual experience, and 70.7% of those used condoms. Those who thought condoms to be protective against HIV, and those who thought they are difficult to wear, were more likely to have sexual experience. The perception of condom use as important, and the perception that condoms are difficult to wear, were predictors of condom carrying. The participants' knowledge of the risk of HIV in vaginal intercourse was deficient. Participants did not consider school sex education to be effective in promoting condom use, and recommended the use of graphic, deterrent personal accounts told by youths to encourage wider use of condoms. CONCLUSIONS: Health educators should consider the barriers cited by adolescents and the deterrent techniques they recommend when planning interventions to encourage condom use. PMID- 26137979 TI - Corrigendum. PMID- 26137980 TI - Improved grazing management may increase soil carbon sequestration in temperate steppe. AB - Different grazing strategies impact grassland plant production and may also regulate the soil carbon formation. For a site in semiarid temperate steppe, we studied the effect of combinations of rest, high and moderate grazing pressure over three stages of the growing season, on the process involved in soil carbon sequestration. Results show that constant moderate grazing (MMM) exhibited the highest root production and turnover accumulating the most soil carbon. While deferred grazing (RHM and RMH) sequestered less soil carbon compared to MMM, they showed higher standing root mass, maintained a more desirable pasture composition, and had better ability to retain soil N. Constant high grazing pressure (HHH) caused diminished above- and belowground plant production, more soil N losses and an unfavorable microbial environment and had reduced carbon input. Reducing grazing pressure in the last grazing stage (HHM) still had a negative impact on soil carbon. Regression analyses show that adjusting stocking rate to ~5SE/ha with ~40% vegetation utilization rate can get the most carbon accrual. Overall, the soil carbon sequestration in the temperate grassland is affected by the grazing regime that is applied, and grazing can be altered to improve soil carbon sequestration in the temperate steppe. PMID- 26137981 TI - Tobacco industry sponsored advocates have a different interpretation of science: a response to: Even anti-tobacco studies must be held to basic scientific standards. PMID- 26137982 TI - Factors Associated with Depression Among Mexican Americans Living in U.S.-Mexico Border and Non-Border Areas. AB - Factors associated with CES-D depression among Mexican Americans living on and off the U.S.-Mexico border are examined. Data are from two studies of Mexican American adults. The Border Survey conducted face-to-face interviews in urban U.S.-Mexico border counties of California, Arizona, New Mexico, and Texas (N = 1307). The non-border HABLAS survey conducted face-to-face interviews in Houston, Los Angeles, New York, Philadelphia, and Miami (N = 1288). Both surveys used a multistage cluster sample design with response rates of 67 and 76 %, respectively. The multivariate analysis showed that border residence and higher perceived neighborhood collective efficacy were protective for depression among men. Among men, lower education, unemployment, increased weekly drinking, and poor health status were associated with depression. Among women, alcohol-related problems and poorer health status were also associated with depression. Further examinations of how neighborhood perceptions vary by gender and how these perceptions influence the likelihood of depression are warranted. PMID- 26137984 TI - Communication for end-of-life care planning among Korean patients with terminal cancer: A context-oriented model. AB - OBJECTIVE: In Korea, patients with terminal cancer are often caught out of the loop in end-of-life (EoL) care discussions. Healthcare professionals also have difficulty engaging in such communication in a variety of healthcare contexts. Therefore, the objective of our study was to develop a communication model for EoL care decision making compatible with the clinical environment in Korea. METHODS: Using focus-group interview methodology, participants included eight doctors and five nurses who provide EoL care for terminal cancer patients in acute hospital settings or hospice care facilities in various provinces of Korea. RESULTS: Five themes emerged regarding EoL care discussion, which included: (1) timing, (2) responsible professionals, (3) disclosure of bad news, (4) content areas of EoL care discussion, and (5) implementing strategies for EoL care discussions. These themes were based on development of a communication algorithm for EoL discussion among patients with terminal cancer. A structural communication step for delivery of a terminal prognosis was specified at the phase of disclosure of bad news: beginning with determination of a patient's decision-making capability, followed by a patient's perception of his/her condition, a patient's wish to know, family dynamics, and a patient's and/or family's readiness for EoL discussions. SIGNIFICANCE OF RESULTS: The proposed context-oriented communication algorithm could provide a helpful guideline for EoL communication and, accordingly, facilitate meaningful improvements in EoL care in Korean clinical practice. The feasibility of this algorithm has not yet been determined, and its validation in a larger sample of patients with terminal cancers, using a quantitative research methodology, is a priority of research. PMID- 26137983 TI - Individual and Contextual Factors Associated with Immigrant Youth Feeling Unsafe in School: A Social-Ecological Analysis. AB - Despite the increasing proportion of immigrant youth in U.S. school districts, no studies have investigated their perceptions of their school. This study examines factors associated with perceptions of school safety among immigrant youth within individual, family, peer, and school contexts. Data were drawn from Wave II of the Children of Immigrants Longitudinal Study (n = 4288) and hierarchical logistic regression analyses were conducted. African-Americans, females, and youth with limited English proficiency were more likely to perceive their school as unsafe. Youth who reported that family cohesion was important and those who had close friends perceived their school as safe. Also, those who experienced illegal activities in school reported feeling unsafe. Assessment and intervention in schools needs to consider individual and contextual factors associated with perceptions of school safety. Additional research is needed to examine individual and contextual factors related to immigrant youths' perceptions of school. PMID- 26137985 TI - Reliability testing of oxaliplatin-associated neurotoxicity questionnaire (OANQ), a pilot study. AB - PURPOSE: The purpose of this study was to test the reliability of the Swedish version of the Oxaliplatin-Associated Neurotoxicity Questionnaire (OANQ) administrated throughout a self-reported mobile phone-based system, a pilot study. METHODS: Twenty-three patients from two university hospitals and two regional hospitals who had been treated with oxaliplatin were included through purposive sampling between autumn 2013 to autumn 2014. A test-retest was performed through a mobile phone-based system, with a recall period of 1 h to determine the reliability of the questionnaire. RESULTS: Internal consistency was strong for the three domains of the scale (alpha > 0.840). The statistical analyses for the test-retest indicated that the OANQ was stable. Intraclass correlation (ICC) for symptom items and effect on daily activities items showed an overall excellent reproducibility at 69 and 83 %, respectively. The weighted kappa for symptom items and daily activities items showed an overall almost perfect agreement at 59 and 52 %, respectively. A paired samples t test did not reveal any significant differences between the two measures. CONCLUSIONS: The OANQ was tested and considered a reliable assessment for capturing the oxaliplatin-induced peripheral neurotoxicity (OIPN) in patients receiving oxaliplatin. However, further reliability testing of the OANQ is needed. PMID- 26137987 TI - Self-oocyte activation and parthenogenesis: an unusual outcome of a misconducted IVF cycle. AB - A rare cause of infertility is the lack of fertilisation with the spontaneous activation of oocytes, leading to parthenogenesis. We present such a case. The patient was a G1P0 38-year-old woman of African ethnicity, who requested an in vitro fertilisation (IVF) with donor sperm. She received a stimulation protocol of 75 IU of FSH/LH from day 3 of the cycle, which she interrupted after 2 d, and restarted with the same dosage for another 3 d from day 7, plus one administration of GnRH antagonist in day 10 of the cycle. With a follicle reaching 19 mm on day 11, estradiol of 325 ng/ml, ovulation was induced with hMG 5000 UI, and oocyte pick-up performed at 30 h. One oocyte was retrieved, and good quality sperms were added to the insemination procedure. No fecundation occurred at 20 h, with the extruded oocyte separated from the granulosa wall. At 40 h and 64 h the aspect was of three cells, one cell with one nucleus, the others with high granulation and no visible nuclei. This case shows an unusual self activation oocyte in a poorly managed IVF cycle. The patient will be further evaluated, to decide if a better managed stimulation protocol would prevent recurrence. PMID- 26137986 TI - Quantitative benefit-harm assessment for setting research priorities: the example of roflumilast for patients with COPD. AB - BACKGROUND: When faced with uncertainties about the effects of medical interventions regulatory agencies, guideline developers, clinicians, and researchers commonly ask for more research, and in particular for more randomized trials. The conduct of additional randomized trials is, however, sometimes not the most efficient way to reduce uncertainty. Instead, approaches such as value of information analysis or other approaches should be used to prioritize research that will most likely reduce uncertainty and inform decisions. DISCUSSION: In situations where additional research for specific interventions needs to be prioritized, we propose the use of quantitative benefit-harm assessments that illustrate how the benefit-harm balance may change as a consequence of additional research. The example of roflumilast for patients with chronic obstructive pulmonary disease shows that additional research on patient preferences (e.g., how important are exacerbations relative to psychiatric harms?) or outcome risks (e.g., what is the incidence of psychiatric outcomes in patients with chronic obstructive pulmonary disease without treatment?) is sometimes more valuable than additional randomized trials. We propose that quantitative benefit-harm assessments have the potential to explore the impact of additional research and to identify research priorities Our approach may be seen as another type of value of information analysis and as a useful approach to stimulate specific new research that has the potential to change current estimates of the benefit-harm balance and decision making. PMID- 26137989 TI - Prognostic factor analysis of vitrectomy for myopic foveoschisis. AB - PURPOSE: To describe the anatomical and functional outcomes in a cohort of subjects undergoing vitrectomy for myopic foveoschisis, and to analyse the factors predicting foveal reattachment and visual improvement. METHODS: This retrospective case series evaluated case records and optical coherence tomography images 6 months after surgery. Multivariate linear and logistic regressions were performed to assess the factors predicting anatomical and visual improvement. RESULTS: In total, 55 eyes of 54 patients were analysed. The mean spherical equivalent refraction was -11.83+/-4.94D. Foveal detachment was present in 63.5% of eyes preoperatively and subjects with foveal detachment had 0.70 logMAR units (95% CI 0.02 to 1.39) poorer visual acuity than subjects without (p=0.046). The mean preoperative visual acuity was 0.84+/-0.59 logMAR units and the mean postoperative visual acuity was 0.64+/-0.64 logMAR units (mean difference 0.20+/ 0.68 logMAR units (p=0.04)). The proportion of eyes with foveal detachment was significantly lower after surgery (12.5%; p<0.001). However, the proportion of eyes with ellipsoid zone disruption was significantly higher after surgery (59.6% vs 34.0%; p<0.001). In multivariate analyses, the preoperative central foveal thickness significantly predicted postoperative visual improvement by two or more lines (OR 1.004 (95% CI 1.000 to 1.007), per MUm increase; p=0.049). The presence of ellipsoid zone disruption preoperatively was associated with 0.96 logMAR (95% CI 0.2 to 1.72) poorer final acuity (p=0.02). CONCLUSIONS: Eyes with myopic foveoschisis with preoperative ellipsoid disruption and thinner central foveal thickness tend to have poorer visual outcomes. While current surgical manoeuvres are effective in reattaching the fovea, they may also cause iatrogenic injury to the photoreceptors. PMID- 26137988 TI - Genome sequence of Valsa canker pathogens uncovers a potential adaptation of colonization of woody bark. AB - Canker caused by ascomycetous Valsa species are among the most destructive diseases of woody plants worldwide. These pathogens are distinct from other pathogens because they only effectively attack tree bark in the field. To unravel the potential adaptation mechanism of bark colonization, we examined the genomes of Valsa mali and Valsa pyri that preferentially infect apple and pear, respectively. We reported the 44.7 and 35.7 Mb genomes of V. mali and V. pyri, respectively. We also identified the potential genomic determinants of wood colonization by comparing them with related cereal pathogens. Both genomes encode a plethora of pathogenicity-related genes involved in plant cell wall degradation and secondary metabolite biosynthesis. In order to adapt to the nutrient limitation and low pH environment in bark, they seem to employ membrane transporters associated with nitrogen uptake and secrete proteases predominantly with acidic pH optima. Remarkably, both Valsa genomes are especially suited for pectin decomposition, but are limited in lignocellulose and cutin degradation. Besides many similarities, the two genomes show distinct variations in many secondary metabolism gene clusters. Our results show a potential adaptation of Valsa canker pathogens to colonize woody bark. Secondary metabolism gene clusters are probably responsible for this host specificity. PMID- 26137990 TI - Association between the prevalence of obstructive sleep apnoea and the severity of keratoconus. AB - AIM: The purpose of this study was to determine the association between prevalence of obstructive sleep apnoea (OSA) in patients with keratoconus (KC) and the severity of KC. METHODS: Six-hundred and sixteen patients with KC and 616 patients without KC in the control group were enrolled in this prospective case control study. Both groups were matched by age, gender, and body mass index (BMI). The Berlin Questionnaire was administered in both groups. Keratometric and topographic measurements of the KC eyes were recorded. RESULTS: Seventy-six (12.3%) and 40 (6.5%) patients were identified as high risk for developing OSA in KC and control groups, respectively (p<0.001). Family history of OSA and BMI were the risk factors for OSA in the KC group, while in the control group the only risk factor for OSA was the patient's gender. Patients with KC with a high risk of OSA had a significantly higher mean K, flat K, steep K (p<0.05), and a thinner corneal thickness (p<0.05). The severity of KC decreased in both OSA groups except for the grade 4 of high risk group which was the second most frequent group after grade 1 (p=0.005). CONCLUSIONS: Our study revealed that patients with KC are at increased risk of developing OSA, and patients with KC who are at higher risk of developing OSA may have more severe KC. PMID- 26137991 TI - Pre-morbid type 2 diabetes mellitus as a prognostic factor in amyotrophic lateral sclerosis. PMID- 26137992 TI - Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. AB - Activation of androgen receptor (AR) is crucial for prostate cancer growth. Remarkably, also castration-resistant prostate cancer (CRPC) is dependent on functional AR, and several mechanisms have been proposed to explain the addiction. Known causes of CRPC include gene amplification and overexpression as well as point mutations of AR. We report here the pharmacological profile of ODM 201, a novel AR inhibitor that showed significant antitumor activity and a favorable safety profile in phase 1/2 studies in men with CRPC. ODM-201 is a full and high-affinity AR antagonist that, similar to second-generation antiandrogens enzalutamide and ARN-509, inhibits testosterone-induced nuclear translocation of AR. Importantly, ODM-201 also blocks the activity of the tested mutant ARs arising in response to antiandrogen therapies, including the F876L mutation that confers resistance to enzalutamide and ARN-509. In addition, ODM-201 reduces the growth of AR-overexpressing VCaP prostate cancer cells both in vitro and in a castration-resistant VCaP xenograft model. In contrast to other antiandrogens, ODM-201 shows negligible brain penetrance and does not increase serum testosterone levels in mice. In conclusion, ODM-201 is a potent AR inhibitor that overcomes resistance to AR-targeted therapies by antagonizing both overexpressed and mutated ARs. ODM-201 is currently in a phase 3 trial in CRPC. PMID- 26137994 TI - Growth, Quantitative Growth Analysis, and Applications of Graphene on gamma-Al2O3 catalysts. AB - The possibilities offered by catalytic gamma-Al2O3 substrates are explored, and the mechanism governing graphene formation thereon is elucidated using both numerical simulations and experiments. The growth scheme offers metal-free synthesis at low temperature, grain-size customization, large-area uniformity of electrical properties, single-step preparation of graphene/dielectric structures, and readily detachable graphene. We quantify based on thermodynamic principles the activation energies associated with graphene nucleation/growth on gamma Al2O3, verifying the low physical and chemical barriers. Importantly, we derive a universal equation governing the adsorption-based synthesis of graphene over a wide range of temperatures in both catalytic and spontaneous growth regimes. Experimental results support the equation, highlighting the catalytic function of gamma-Al2O3 at low temperatures. The synthesized graphene is manually incorporated as a 'graphene sticker' into an ultrafast mode-locked laser. PMID- 26137995 TI - The long and winding road in cancer survivorship care. PMID- 26137996 TI - The Africa Center for Biostatistical Excellence: a proposal for enhancing biostatistics capacity for sub-Saharan Africa. AB - Sub-Saharan Africa has a shortage of well-trained biomedical research methodologists, in particular, biostatisticians. In July 2014, a group of biostatisticians and researchers from the region attended a brainstorming workshop to identify ways in which to reduce the deficit in this critical skill. The workshop recognized that recommendations from previous workshops on building biostatistics capacity in sub-Saharan Africa had not been implemented. The discussions culminated with a proposal to setup an Africa Center for Biostatistical Excellence, a collaborative effort across academic and researcher institutions within the region, as a vehicle for promoting biostatistics capacity building through specialized academic masters programs as well as regular workshops targeting researchers. PMID- 26137993 TI - Targeted capture in evolutionary and ecological genomics. AB - The rapid expansion of next-generation sequencing has yielded a powerful array of tools to address fundamental biological questions at a scale that was inconceivable just a few years ago. Various genome-partitioning strategies to sequence select subsets of the genome have emerged as powerful alternatives to whole-genome sequencing in ecological and evolutionary genomic studies. High throughput targeted capture is one such strategy that involves the parallel enrichment of preselected genomic regions of interest. The growing use of targeted capture demonstrates its potential power to address a range of research questions, yet these approaches have yet to expand broadly across laboratories focused on evolutionary and ecological genomics. In part, the use of targeted capture has been hindered by the logistics of capture design and implementation in species without established reference genomes. Here we aim to (i) increase the accessibility of targeted capture to researchers working in nonmodel taxa by discussing capture methods that circumvent the need of a reference genome, (ii) highlight the evolutionary and ecological applications where this approach is emerging as a powerful sequencing strategy and (iii) discuss the future of targeted capture and other genome-partitioning approaches in the light of the increasing accessibility of whole-genome sequencing. Given the practical advantages and increasing feasibility of high-throughput targeted capture, we anticipate an ongoing expansion of capture-based approaches in evolutionary and ecological research, synergistic with an expansion of whole-genome sequencing. PMID- 26137998 TI - Hierarchical porous anatase TiO2 derived from a titanium metal-organic framework as a superior anode material for lithium ion batteries. AB - Hierarchical meso-/macroporous anatase TiO2 was synthesized by the hydrolysis of a titanium metal-organic framework precursor followed by calcination in air. This unique porous feature enables the superior rate capability and excellent cycling stability of anatase TiO2 as an anode for rechargeable lithium-ion batteries. PMID- 26137997 TI - Candida Surveillance in Surgical Intensive Care Unit (SICU) in a Tertiary Institution. AB - BACKGROUND: Colonization of patients occurs before development into invasive candidiasis. There is a need to determine the incidences of Candida colonization and infection in SICU patients, and evaluate the usefulness of beta-D-glucan (BDG) assay in diagnosing invasive candidiasis when patients are colonized. METHODS: Clinical data and fungal surveillance cultures in 28 patients were recorded from November 2010, and January to February 2011. Susceptibilities of Candida isolates to fluconazole, voriconazole, amphotericin B, micafungin, caspofungin and anidulafungin were tested via Etest. The utilities of BDG, Candida score and colonization index for candidiasis diagnosis were compared via ROC. RESULTS: 30 BDG assays were performed in 28 patients. Four assay cases had concurrent colonization and infection; 23 had concurrent colonization and no infection; three had no concurrent colonization and infection. Of 136 surveillance swabs, 52 (38.24 %) were positive for Candida spp, with C. albicans being the commonest. Azole resistance was detected in C. albicans (7 %). C. glabrata and C. tropicalis were, respectively, 100 and 7 % SDD to fluconazole. All 3 tests showed high sensitivity of 75-100 % but poor specificity ranging 15.38-38.46 %. BDG performed the best (AUC of 0.89). CONCLUSIONS: Despite that positive BDG is common in surgical patients with Candida spp colonization, BDG performed the best when compared to CI and CS. PMID- 26137999 TI - The Effect of Direct Current Stimulation versus T-Wave Shock on Defibrillation Threshold Testing. AB - INTRODUCTION: There are several methods to induce ventricular fibrillation (VF) during defibrillation threshold (DFT) testing. Delivering a shock at a critical time during the T wave (T-shock) is the conventional approach, while delivering a constant direct current voltage (DC stim) from the implantable cardioverter defibrillator is an alternative method. Only a few reports compare VF induction methods. The purpose of this study was to evaluate the effects and safety of DC stim versus T-shock. METHODS: We retrospectively investigated 414 consecutive patients undergoing DFT testing. We compared the two groups (DC stim and T-shock) with respect to clinical characteristics, electrocardiogram (ECG) changes, and complications. RESULTS: Ventricular arrhythmia, including ventricular tachycardia (VT) and VF, was induced by DC stim in 93 patients or T-shock in 321 patients. No more than three attempts were performed during one procedure. There was no significant difference in the baseline ECG, induced tachycardia cycle length (TCL), or complications between the two groups. However, the induced TCL was significantly shorter than the clinical TCL regardless of induction method (P = 0.001). Five patients suffered major complications (i.e., electromechanical dissociation or incessant VT). A history of atrial fibrillation was significantly greater in patients with major complications than the others (80% vs 24%, P = 0.004), and was an independent predictor on multivariate analysis. CONCLUSIONS: There is no significant difference in induced TCL or complications between the DC stim and T-shock. The induced TCL is significantly shorter than clinical TCL regardless of induction method. PMID- 26138000 TI - Ultra-broadband and high response of the Bi2Te3-Si heterojunction and its application as a photodetector at room temperature in harsh working environments. AB - Broadband photodetection is central to various technological applications including imaging, sensing and optical communications. On account of their Dirac like surface state, Topological insulators (TIs) are theoretically predicted to be promising candidate materials for broadband photodetection from the infrared to the terahertz. Here, we report a vertically-constructed ultra-broadband photodetector based on a TI Bi2Te3-Si heterostructure. The device demonstrated room-temperature photodetection from the ultraviolet (370.6 nm) to terahertz (118 MUm) with good reproducibility. Under bias conditions, the visible responsivity reaches ca. 1 A W(-1) and the response time is better than 100 ms. As a self powered photodetector, it exhibits extremely high photosensitivity approaching 7.5 * 10(5) cm(2) W(-1), and decent detectivity as high as 2.5 * 10(11) cm Hz(1/2) W(-1). In addition, such a prototype device without any encapsulation suffers no obvious degradation after long-time exposure to air, high-energy UV illumination and acidic treatment. In summary, we demonstrate that TI-based heterostructures hold great promise for addressing the long lasting predicament of stable room-temperature high-performance broadband photodetectors. PMID- 26138001 TI - Distinctive Effect of Donepezil Treatment on P300 and N200 Subcomponents of Auditory Event-Related Evoked Potentials in Alzheimer Disease Patients. AB - BACKGROUND: Latency of P300 subcomponent of event-related potentials (ERPs) increases in Alzheimer disease (AD) patients, which correlate well with cognitive impairment. Cholinesterase inhibitors (ChEIs) reduce P300 latency in AD patients with parallel improvement in cognition. It is not known whether N200 response to ChEIs is similar to that of P300. The aim of this study was to evaluate and compare characteristics of P300 and N200 in AD patients, treatment-naive and on stable donepezil treatment, matched by age, education, sex, and cognitive function. MATERIAL AND METHODS: We recruited 22 consecutive treatment-naive AD patients (AD-N group), 22 AD patients treated with a stable donepezil dose of 10 mg/day for at least 3 months (AD-T group), and 50 healthy controls were recruited. Neuropsychological testing (MMSE, ADAS-Cog, and additional tests) and ERP recording was performed and analyzed. RESULTS: All groups did not differ according to age, duration of education, or sex (p>0.05). AD-N and AD-T groups did not differ according to cognitive function. The AD-T group had longer duration of disease than the AD-N group (p<0.001). The AD-T and AD-N groups did not differ in P300 latencies (p=0.49). N200 latency was longer in the AD-T group (p<0.001). The general linear model showed that significant predictors of P300 latency were age (p=0.019) and AD treatment status (p<0.001). Duration of AD was a significant predictor of N200 latency (p=0.004). CONCLUSIONS: The response of N200 latency to donepezil treatment differs from the response of P300. P300 is a better marker of ChEI treatment-dependent cognitive functions. N200 is more dependent on the duration of AD. PMID- 26138002 TI - Tracheobronchial smooth muscle atrophy and separation. AB - We report a case series involving 4 patients with chronic obstructive pulmonary disease who were on an appropriate medical regimen including a high dose of inhaled corticosteroids (ICS). During bronchoscopy, patients were found to have an excessive dynamic collapse of the posterior wall and its separation from the ends of the adjacent cartilaginous rings. This was causing a near-total occlusion of the tracheal and bronchial lumen during exhalation, thereby presenting with an obstructive pattern on the pulmonary functions. We suspect that this was caused by the atrophy of the smooth muscles of the tracheobronchial wall. We reviewed the literature to explore the mechanisms causing atrophy of the bronchial smooth muscle, focusing on the potential role of long-term ICS use. PMID- 26138003 TI - Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression. AB - OBJECTIVE: To investigate the role of hippocampal plasticity in the antidepressant effect of electroconvulsive therapy (ECT). METHOD: We used magnetic resonance (MR) imaging including diffusion tensor imaging (DTI) and proton MR spectroscopy (1 H-MRS) to investigate hippocampal volume, diffusivity, and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), 1 week (TP2), and 4 weeks (TP3) after ECT. RESULTS: Hippocampal and amygdala volume increased significantly at TP2 and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post-ECT changes in brain metabolite concentrations, and we were unable to identify a spectral signature at ~1.30 ppm previously suggested to reflect neurogenesis induced by ECT. None of the brain imaging measures correlated to the clinical response. CONCLUSION: Our findings show that ECT causes a remodeling of brain structures involved in affective regulation, but due to their lack of correlation with the antidepressant effect, this remodeling does not appear to be directly underlying the antidepressant action of ECT. PMID- 26138004 TI - Vegetarian Diets and Weight Reduction: a Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Vegetarian diets may promote weight loss, but evidence remains inconclusive. METHODS: PubMed, EMBASE and UpToDate databases were searched through September 22, 2014, and investigators extracted data regarding study characteristics and assessed study quality among selected randomized clinical trials. Population size, demographic (i.e., gender and age) and anthropometric (i.e., body mass index) characteristics, types of interventions, follow-up periods, and trial quality (Jadad score) were recorded. The net changes in body weight of subjects were analyzed and pooled after assessing heterogeneity with a random effects model. Subgroup analysis was performed based on type of vegetarian diet, type of energy restriction, study population, and follow-up period. RESULTS: Twelve randomized controlled trials were included, involving a total of 1151 subjects who received the intervention over a median duration of 18 weeks. Overall, individuals assigned to the vegetarian diet groups lost significantly more weight than those assigned to the non-vegetarian diet groups (weighted mean difference, -2.02 kg; 95 % confidence interval [CI]: -2.80 to -1.23). Subgroup analysis detected significant weight reduction in subjects consuming a vegan diet (-2.52 kg; 95 % CI: -3.02 to -1.98) and, to a lesser extent, in those given lacto ovo-vegetarian diets (-1.48 kg; 95 % CI: -3.43 to 0.47). Studies on subjects consuming vegetarian diets with energy restriction (ER) revealed a significantly greater weight reduction (-2.21 kg; 95 % CI: -3.31 to -1.12) than those without ER (-1.66 kg; 95 % CI: -2.85 to -0.48). The weight loss for subjects with follow up of <1 year was greater (-2.05 kg; 95 % CI: -2.85 to -1.25) than those with follow-up of >=1 year (-1.13 kg; 95 % CI: -2.04 to -0.21). CONCLUSIONS: Vegetarian diets appeared to have significant benefits on weight reduction compared to non-vegetarian diets. Further long-term trials are needed to investigate the effects of vegetarian diets on body weight control. PMID- 26138005 TI - Erratum to: Choosing Wisely: Prevalence and Correlates of Low-Value Health Care Services in the United States. PMID- 26138007 TI - The Value of Narrative Medical Writing in Internal Medicine Residency. AB - Narrative medical writing can be utilized to help increase the value and patient centeredness of health care. By supporting initiatives in areas such as population health management, quality improvement and health disparities, it provides benefits that are particularly relevant to physicians focused on health care improvement, reform and redesign. Graduate medical education (GME) represents a key time and opportunity for internists to learn and practice this form of writing. However, due to a number of local and systems factors, many have limited opportunities to engage in narrative medical writing compared to other non-clinical activities. By capitalizing on the momentum created by recent GME reform, several strategies can be utilized to overcome these barriers and establish narrative medical writing as a viable professional and communication skill. PMID- 26138008 TI - Cross-fertilization as a reproductive strategy in a tissue flukes Didymosulcus katsuwonicola (Platyhelmintes: Didymozoidae) inferred by genetic analysis. AB - Mitochondrial DNA locus cytochrome oxidase I was used to asses intraspecific genetic diversity of a didymozoid species Didymosulcus katsuwonicola. Adult forms of this species live encapsulated in pairs in the gills of the reared Atlantic bluefin tuna (Thunnus thynnus). The life cycle of this food-borne parasites and its migration in the host tissues after releasing from the digestive tract to the definitive site in the gills are unknown. Our goal was to assess whether two encysted didymozoids share the same haplotype, indicative of a common maternal origin, as well as the extent of cross- in respect to self-fertilization strategy. Intraspecific comparison showed high haplotype diversity, while the presence of two matching haplotypes within a single cyst encompassed only 17% of sampled individuals. This infers that cross-fertilization between paired individuals within the cyst is more common mechanism than self-fertilization. Such hermaphroditic parasite's trait suggests the existence of intricate infection and reproduction mechanisms, presumably as an adaptation for successful fulfillment of their indirect life cycle through dissemination of genetically more diverse and consequently more fit offspring. PMID- 26138006 TI - Influence of Nephrologist Care on Management and Outcomes in Adults with Chronic Kidney Disease. AB - BACKGROUND: Predialysis nephrology care for adults with late stage chronic kidney disease (CKD) is associated with improved outcomes. Less is known about the effects of nephrology care in earlier stages of CKD. OBJECTIVE: We aimed to evaluate the effect of nephrology care on management of CKD risk factors and complications, CKD progression, incident cardiovascular disease (CVD), and death. DESIGN: This was a prospective cohort study. PARTICIPANTS: Participants included 3855 men and women aged 21 to 74 years enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study with a mean (SD) estimated glomerular filtration rate (eGFR) at entry of 45 (17) ml/min/1.73 m(2), followed for a median of 6.6 years. MAIN MEASURES: The main predictor was self-reported prior contact with a nephrologist at study enrollment. Outcomes evaluated included CKD progression (>= 50 % eGFR loss or end-stage renal disease), incident CVD, and death. RESULTS: Two-thirds (67 %) of the participants reported prior contact with a nephrologist at study enrollment. They were younger, more likely to be male, non-Hispanic white, and had lower eGFR and higher urine protein (p < 0.05). A subgroup with eGFR 30- < 60 ml/min/1.73 m(2) and prior contact with a nephrologist were more likely to receive pharmacologic treatment for CKD-related complications and to report angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) use. After propensity score matching (for reporting prior contact with a nephrologist vs. not) and adjusting for demographic and clinical variables, prior contact with a nephrologist was not significantly associated with CKD progression, incident CVD or death (p > 0.05). CONCLUSIONS: One-third of CRIC participants had not seen a nephrologist before enrollment, and this prior contact was subject to age, sex, and ethnic-related disparities. While prior nephrology care was associated with more frequent treatment of CKD complications and use of ACEi/ARB medications, there was neither an association between this care and achievement of guideline-recommended intermediate measures, nor long-term adverse outcomes. PMID- 26138009 TI - Recognition of human telomeric G-quadruplex DNA by berberine analogs: effect of substitution at the 9 and 13 positions of the isoquinoline moiety. AB - G-quadruplex forming sequences are widely distributed in human genome and serve as novel targets for regulating gene expression and chromosomal maintenance. They offer unique targets for anticancer drug development. Here, the interaction of berberine (BC) and two of its analogs bearing substitution at 9 and 13-position with human telomeric G-quadruplex DNA sequence has been investigated by biophysical techniques. Both the analogs exhibited several-fold higher binding affinity than berberine. The Scatchard binding isotherms revealed non-cooperative binding. 9-omega-amino hexyl ether analog (BC1) showed highest affinity (1.8 * 10(6) M(-1)) while the affinity of the 13-phenylpropyl analog (BC2) was 1.09 * 10(6) M(-1). Comparative fluorescence quenching and polarization anisotropy of the emission spectra gave evidence for a stronger stacking interaction of the analogs compared to berberine. The thiazole orange displacement assay has clearly established that the analogs were more effective in displacing the end stacked dye in comparison to berberine. However, the binding of the analogs did not induce any major structural perturbation in the G-quadruplex structure, but led to higher thermal stability. Energetics of the binding indicated that the association of the analogs was exothermic and predominantly entropy driven phenomenon. Increasing the temperature resulted in weaker binding; the enthalpic contribution increased and the entropic contribution decreased. A small negative heat capacity change with significant enthalpy-entropy compensation established the involvement of multiple weak noncovalent interactions in the binding process. The 9-omega-amino hexyl ether analog stabilized the G-quadruplex structure better than the 13-phenyl alkyl analog. PMID- 26138010 TI - Aluminum Chloride Induces Osteoblasts Apoptosis via Disrupting Calcium Homeostasis and Activating Ca(2+)/CaMKII Signal Pathway. AB - Aluminum promotes osteoblast (OB) apoptosis. Apoptosis is induced by the disordered calcium homeostasis. Therefore, to investigate the relationship between Al-induced OB apoptosis and calcium homeostasis, calvarium OBs from neonatal rats (3-4 days) were cultured and exposed to 0.048-mg/mL Al(3+) or 0.048 mg/mL Al(3+) combined with 5 MUM BAPTA-AM (OBs were pretreated with 5 MUM BAPTA AM for 1 h, then added 0.048 mg/mL Al(3+)), respectively. Then OB apoptosis rate, intracellular calcium ions concentration ([Ca(2+)]i), mRNA expression level of calmodulin (CaM), and protein expression levels of CaM and p-CaMKII in OBs were examined. The result showed that AlCl3 increased OB apoptosis rate, and [Ca(2+)]i and p-CaMKII expression levels and decreased CaM expression levels, whereas BAPTA AM relieved the effects. These results proved that AlCl3 induced OB apoptosis by disrupting the intracellular Ca(2+) homeostasis and activating the Ca(2+)/CaMKII signal pathway. Our findings can provide new insights for revealing the apoptosis mechanism of OBs exposed to AlCl3. PMID- 26138011 TI - Intracellular Zn(2+) Increase in Cardiomyocytes Induces both Electrical and Mechanical Dysfunction in Heart via Endogenous Generation of Reactive Nitrogen Species. AB - Oxidants increase intracellular free Zn(2+) concentration ([Zn(2+)]i) in ventricular myocytes, which contributes to oxidant-induced alterations in excitation-contraction coupling (ECC). However, it is not clear whether increased [Zn(2+)]i in cardiomyocytes via increased reactive nitrogen species (RNS) has a role on heart function under pathological conditions, such as hyperglycemia. In this study, first we aimed to investigate the role of increased [Zn(2+)]i under in vitro condition in the development of both electrical and mechanical dysfunction of isolated papillary muscle strips from rat heart via exposed samples to a Zn(2+)-ionophore (Zn-pyrithione; 1 MUM) for 20 min. Under simultaneous measurement of intracellular action potential and contractile activity in these preparations, Zn-pyrithione exposure caused marked prolongation in action potential repolarization phase and slowdown in both contraction and relaxation rates of twitch activity. Second, in order to demonstrate an association between increased [Zn(2+)]i and increased RNS, we monitored intracellular [Zn(2+)]i under an acute exposure of nitric oxide (NO) donor sodium nitroprusside, SNP, in freshly isolated quiescent cardiomyocytes loaded with FluoZin-3. Resting level of free Zn(2+) is significantly higher in cardiomyocytes under hyperglycemic condition compared to those of the controls, which seems to be associated with increased level of RNS production in hyperglycemic cardiomyocytes. Western blot analysis showed that Zn-pyrithione exposure induced a marked decrease in the activity of protein phosphatase 1 and 2A, member of macromolecular protein complex of cardiac ryanodine receptors, RyR2, besides significant increase in the phosphorylation level of extracellular signal regulated kinase1/2 as a concentration-dependent manner. Overall, the present data demonstrated that there is a cross-relationship between increased RNS production and increased [Zn(2+)]i level in cardiomyocytes under pathological conditions such as hyperglycemia. PMID- 26138012 TI - Will shorter time interval to diagnose ovarian cancer improve early detection? A perspective from the dualistic model. PMID- 26138013 TI - [Management of complications after revascularization due to peripheral arterial occlusive disease : Prophylaxis and consistent adequate therapy after timely diagnostics]. AB - BACKGROUND: Complications are a threat to successful revascularization for treatment of perpheral arterial occlusive disease (PAOD) and must, therefore, be either primarily prevented or effectively treated after having occurred. OBJECTIVES: The aim of this article is to give a survey of possible complications after revascularization for treatment of PAOD and their management. MATERIAL AND METHODS: A systematic literature review was performed in PubMed and Medline. The analysis mainly considered recent publications with a higher level of evidence. RESULTS: Revascularization for treatment of PAOD can basically be performed by an open surgical approach, an endovascular approach or as a combination of both methods (hybrid operation). The spectrum of possible complications varies accordingly. A differentiation can be made between bleeding, ischemic and systemic complications as well as between vascular and non-vascular complications. Optimal management of complications begins with primary prophylaxis and further includes a timely diagnosis and treatment of established complications. The best prophylaxis consists of a high quality of indications and performance of revascularization. CONCLUSION: Optimal management of complications is essential and of utmost importance for successful revascularization to treat PAOD. PMID- 26138015 TI - Inverted left atrial appendage: a complication of de-airing during cardiac surgery. PMID- 26138014 TI - Modulation of cytokines and chemokines expression by NAC in cadmium chloride treated human lung cells. AB - Cadmium (Cd), is one of the most hazardous metals found in the environment. Cd exposure through inhalation has been linked to various diseases in lungs. It was shown that Cd induces proinflammatory cytokines through oxidative stress mechanism. In this report, we studied the immunomodulatory effect of a well known antioxidant, N-acetylcysteine (NAC) on cadmium chloride (CdCl2 ) treated human lung A549 cells through human cytokine array 6. The lung cells were treated with 0 or 75 uM CdCl2 alone, 2.5 mM NAC alone, or co-treated with 2.5 mM NAC and 75 uM CdCl2 for 24 h. The viability of cells was measured by crystal violet dye. The array results were validated by human IL-1alpha enzyme- linked immunosorbent assay (ELISA) kit. The viability of the 75 uM CdCl2 alone treated cells was decreased to 44.5%, while the viability of the co-treated cells with 2.5 mM NAC was increased to 84.1% in comparison with untreated cells. In the cell lysate of CdCl2 alone treated cells, 19 and 8 cytokines were up and down-regulated, while in the medium 15 and 3 cytokines were up and downregulated in comparison with the untreated cells. In the co-treated cells, all these cytokines expression was modulated by the NAC treatment. The IL-1alpha ELISA result showed the same pattern of cytokine expression as the cytokine array. This study clearly showed the modulatory effect of NAC on cytokines and chemokines expression in CdCl2- treated cells and suggests the use of NAC as protective agent against cadmium toxicity. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1612-1619, 2016. PMID- 26138017 TI - Burden of benign prostatic hyperplasia among men in Japan: Patient-reported outcomes among those diagnosed and experiencing symptoms. AB - OBJECTIVES: To quantify the burden of benign prostatic hyperplasia among Japanese men according to patient-reported outcomes. A secondary aim was to quantify the incremental burden of nocturia among these men. METHODS: Survey data representative of the Japanese population by age and sex were analyzed (total n = 59 997). All measures were self-reported, including the revised Medical Outcomes Study 12-Item Short Form Health Survey or the revised Medical Outcomes Study 36 Item Short Form Health Survey, Work Productivity and Activity Impairment questionnaire, and 6-month healthcare use. Men aged >=50 years were organized into three analysis groups according to diagnosis of benign prostatic hyperplasia and International Prostate Symptom Score total: diagnosed benign prostatic hyperplasia (n = 1183); undiagnosed benign prostatic hyperplasia with moderate to severe symptoms (International Prostate Symptom Score total >=8; n = 3141); and controls (no benign prostatic hyperplasia diagnosis and International Prostate Symptom Score total <8; n = 9468). Subgroup analyses were carried out according to frequency of nocturia. Generalized linear models adjusted for potential confounders. RESULTS: Relative to controls, diagnosed and undiagnosed benign prostatic hyperplasia respondents had reduced health-related quality of life, with mean decrements of >=3.1 points for mental component summary scores, >=2.0 for physical component summary scores and >=0.05 for health utility scores (all P < 0.001). Mean absenteeism, impairment at work and non-work activity impairment among the diagnosed and undiagnosed groups were >=1.4-fold those of the control group (P < 0.01). Both diagnosed and undiagnosed groups used significantly more healthcare than controls. The outcomes of undiagnosed men were worse than diagnosed patients on many measures. Frequent nocturia (>=3 voids per night) was associated with worse health-related quality of life. CONCLUSIONS: Benign prostatic hyperplasia impacts health-related quality of life, work productivity and healthcare use of Japanese men, with more impact among undiagnosed men experiencing lower urinary tract symptoms and frequent nocturia. PMID- 26138016 TI - Physical Function, Hyperuricemia, and Gout in Older Adults. AB - OBJECTIVE: Gout prevalence is high in older adults and those affected are at risk of physical disability, yet it is unclear whether they have worse physical function. METHODS: We studied gout, hyperuricemia, and physical function in 5,819 older adults (age >=65 years) attending the 2011-2013 Atherosclerosis Risk in Communities Study visit, a prospective US population-based cohort. Differences in lower extremity function (Short Physical Performance Battery [SPPB] and 4-meter walking speed) and upper extremity function (grip strength) by gout status and by hyperuricemia prevalence were estimated in adjusted ordinal logistic regression (SPPB) and linear regression (walking speed and grip strength) models. Lower scores or times signify worse function. The prevalence of poor physical performance (first quartile) by gout and hyperuricemia was estimated using adjusted modified Poisson regression. RESULTS: Ten percent of participants reported a history of gout and 21% had hyperuricemia. There was no difference in grip strength by history of gout (P = 0.77). Participants with gout performed worse on the SPPB test; they had 0.77 times (95% confidence interval [95% CI] 0.65, 0.90, P = 0.001) the prevalence odds of a 1-unit increase in SPPB score and were 1.18 times (95% CI 1.07, 1.32, P = 0.002) more likely to have poor SPPB performance. Participants with a history of gout had slower walking speed (mean difference -0.03; 95% CI -0.05, -0.01, P < 0.001) and were 1.19 times (95% CI 1.06, 1.34, P = 0.003) more likely to have poor walking speed. Similarly, SPPB score and walking speed, but not grip strength, were worse in participants with hyperuricemia. CONCLUSION: Older adults with gout and hyperuricemia are more likely to have worse lower extremity, but not upper extremity, function. PMID- 26138019 TI - "Better safe than sorry": a qualitative content analysis of participant's perspectives of fall-related concerns and balance in older women with osteoporosis after balance training. AB - PURPOSE: To explore how older women with osteoporosis perceive fall-related concerns and balance in daily life after having participated in balance training. METHODS: Explorative study. Semi-structured interviews were conducted with 19 women (66-84 years), with osteoporosis recruited from an ongoing RCT; participants were asked about their perceived fall-related concerns and balance. Interviews were taped and transcribed verbatim. Data were analyzed using inductive qualitative content analysis. RESULTS: One underlying theme emerged: "Internalized risk perception related to experience of bodily fragility", and three manifest categories: empowerment, safety and menace. A dynamic process between the categories was found, in which contextual and personal factors influenced perceptions of fall-related concerns and balance, i.e. winter season may lead a person who is highly empowered and/or uses active strategies into a situation of perception of menace and avoidance of activity. CONCLUSION: To cope with the fragility caused by osteoporosis informants had an internalized risk perception that protected them against possible threats and harm. Informants perceived improved empowerment and self-efficacy after participation in balance training. They resumed activities and became more active and independent in daily life using safety precautions and fall-prevention strategies. Depending on contextual factors, some situations still invoked fear and led to avoidance. Implication for Rehabilitation Risk awareness protecting against possible threats and harms seems to be internalized in older women living with osteoporosis. When designing fall prevention programs, it is important to recognize that contextual and personal factors have a major influence on how older women with osteoporosis perceive fall-related concerns and balance. Perception of fragility and risk seems to be a significant problem for older women with osteoporosis and health care providers should encourage their patients to participate in tailored balance training programs to overcome these concerns. PMID- 26138018 TI - Quality of life (QoL) and International Normalized Ratio (INR) control of patients attending anticoagulation clinics. AB - OBJECTIVES: To investigate association between quality of life (QoL) and International Normalized Ratio (INR) control, with the secondary aim of assessing QoL using generic and anticoagulation-specific, the Short Form Health Survey (SF 12) and the Duke Anticoagulation Satisfaction Scale (DASS). STUDY DESIGN: This study assessed anticoagulation related QoL at three time intervals in two groups of patients on long-term warfarin therapy. METHODS: Data of 326 randomly sampled patients (163 patients each in DASS and SF-12 groups) who had been on warfarin therapy for at least one year at anticoagulation clinics were analysed. QoL was assessed at three time intervals: at the start, six months and one year of warfarin therapy. Indications and target INR ranges and subjects INR values were recorded. Time in Therapeutic Range (TTR) was estimated for four subject subgroups, based on target ranges of INR for clustered indications. RESULTS: Of the total, 43% of the subjects were aged between 50 and 64 years, and 51% were female. DASS assessed subjects older than 35 years perceived significant decrease in overall mean scores of anticoagulation related QoL, whilst all SF-12 assessed subjects perceived an increase in QoL. The mean percentage days in range for all INR target range subgroups did not exceed more than 60% but there was only a weak correlation (Rs = 0.104, P > 0.05) between INR control and overall QoL. CONCLUSION: Malaysian urban outpatients on warfarin treatment longer than one year report a significant overall decrease in QoL, as measured using a validated condition-specific instrument. These patients appeared to adapt well to lifestyle limitations imposed by long-term anticoagulation. PMID- 26138020 TI - Living Labs: overview of ecological approaches for health promotion and rehabilitation. AB - PURPOSE: The term "Living Lab" was coined to reflect the use of sensors to monitor human behavior in real life environments. Until recently such measurements had been feasible only within experimental laboratory settings. The objective of this paper is to highlight research on health care sensing and monitoring devices that enable direct, objective and accurate capture of real world functioning. METHOD: Selected articles exemplifying the key technologies that allow monitoring of the motor-cognitive activity of persons with disabilities during naturally occurring daily experiences in real-life settings are discussed in terms of (1) the ways in which the Living Lab approach has been used to date, (2) limitations related to clinical assessment in rehabilitation settings and (3) three categories of the instruments most commonly used for this purpose: personal technologies, ambient technologies and external assistive systems. RESULTS: Technology's most important influences on clinical practice and rehabilitation are in a shift from laboratory-based to field-centered research and a transition between in-clinic performance to daily life activities. Numerous applications show its potential for real-time clinical assessment. CONCLUSIONS: Current technological solutions that may provide clinicians with objective, unobtrusive measurements of health and function, as well as tools that support rehabilitation on an individual basis in natural environments provide an important asset to standard clinical measures. IMPLICATIONS FOR REHABILITATION: Until recently objective clinical assessment could not be readily performed in a client's daily functional environment. Novel technologies enable health care sensing and monitoring devices that enable direct, objective and accurate capture of real-world functioning. Such technologies are referred to as a "Living Lab" approach since they enable the capture of objective and non-obtrusive data that clinicians can use to assess performance. Research and development in this field help clinicians support maintain independence and quality of life for people who have disabilities or who are aging, and to promote more effective methods of long term rehabilitation and maintenance of a healthy life style. PMID- 26138021 TI - Prognostic factors of return to work after traumatic or non-traumatic acquired brain injury. AB - PURPOSE: To investigate and to determine evidence of prognostic factors for return to work (RTW) after acquired brain injury (ABI). METHOD: A systematic literature search was conducted in PubMed (2008-2014), applying terms for ABI and RTW. In addition, studies published after 2003 of a previous review on the same topic were added. The methodological quality of the included studies was assessed and evidence was classified. RESULTS: Twenty-seven studies were included. There is strong evidence that a high education level is positively associated with RTW after traumatic ABI; a low education level, unemployment and length of stay in rehabilitation are negatively associated, and a clear tendency has been deduced from the studies that conscious state in the Emergency Department is not associated with RTW. After non-traumatic ABI, there is strong evidence that independence in activities of daily living is positively associated with RTW and aetiology of stroke is not. CONCLUSIONS: This study confirms earlier findings that after both traumatic and non-traumatic ABI injury related factors in the Emergency Department are not associated with RTW. In addition, it provides further evidence that personal factors after traumatic ABI and activity-related factors after non-traumatic ABI are strongly associated with RTW. Implications for Rehabilitation We found strong evidence for a significant association between RTW and personal factors (education level, unemployment) after traumatic ABI, and activities of daily living (ADL) after non-traumatic ABI. We advise to focus on work-related activities during the RTW process besides ADL-training and pay attention to and support patients at risk for not returning to work. PMID- 26138022 TI - Refinement of the postnatal growth restriction locus of chromosome 5q12-13 deletion syndrome. AB - Individuals with deletions of chromosome 5q12-13 have rarely been reported and have a range of phenotypes including postnatal growth restriction, intellectual disability, hyperactivity, and ocular abnormalities. Most individuals reported have large deletions or complex rearrangements which have made identifying genes responsible for these phenotypes challenging. Here we report an individual with a chromosome 5q12-13 deletion with intellectual disability, hyperactivity and restricted linear growth. Based on the location of our patient's deletion in relation to the previously reported deletions, we have narrowed the locus for postnatal growth restriction to less than 1 megabase. Further refinement of this locus with reports of additional individuals with deletions of this region will allow for better understanding of the gene(s) responsible for this phenotype. PMID- 26138024 TI - Erratum to: The surgical management of chronic subdural hematoma. PMID- 26138023 TI - Lung transplantation after endoscopic lung volume reduction. AB - BACKGROUND: Endoscopic lung volume reduction (ELVR) has become an established treatment option in selected patients with end-stage lung emphysema. ELVR, however, does not always prevent disease progression, and patients may inevitably be considered for lung transplantation. OBJECTIVES: Currently, limited data exist regarding the impact of preceding ELVR on lung transplantation outcomes. METHODS: A retrospective, single-center analysis of lung transplantation (LTx) waiting list candidates, who had previously undergone ELVR for emphysema between 2010 and 2014, was performed. Outcomes were compared to matched (1:2) controls who underwent LTx for emphysema without previous ELVR. The 12-month survival after LTx represented the primary end point. RESULTS: In total 23/693 (3%) patients listed for LTx between January 2010 and May 2014 had undergone ELVR, of whom 20/23 (87%) proceeded to LTx (ELVR group). Forty matched non-ELVR emphysema patients acted as controls. Bronchiectasis on CT prior to LTx was more evident in ELVR patients [11/20 (55%) vs. 12/40 (30%); p = 0.04] as well as airway colonization after LTx [10/20 (50%) vs. 6/40 (15%); p = 0.004]. Among ELVR patients, the most prevalent colonizing organism was Stenotrophomonas maltophilia (4/10 patients, 40%). No significant differences were observed in LTx waiting list time, duration of LTx procedure, ventilatory support, ICU stay after LTx or time to hospital discharge. One ELVR patient (5%) died 189 days after LTx from pneumonia, compared to 1 non-ELVR patient (3%) who died after 269 days (p = 0.61). CONCLUSIONS: Previous ELVR treatment was not associated with differing outcomes following LTx. Increased bacterial colonization rates were evident and warrant further investigation. PMID- 26138025 TI - Poor memory B cell generation contributes to non-protective responses to DTaP vaccine antigens in otitis-prone children. AB - We recently identified a cohort of children with recurrent episodes of acute otitis media (AOM) who fail to generate protective antibody titres to otopathogens and several vaccine antigens. In this study we determined the antibody levels against DTaP vaccine antigens, diphtheria toxoid (DT), tetanus toxoid (TT) and acellular pertussis toxoid (PT) in sera from 15 stringently defined otitis-prone (sOP) children and 20 non-otitis-prone (NOP) children. We found significantly lower concentrations of immunoglobulin (Ig)G antibodies against vaccine antigens in the serum of sOP children compared to age-matched NOP children. To elucidate immunological cellular responses to the vaccines in these children, we investigated memory B cell responses to DTaP vaccination. We used fluorescently conjugated vaccine antigens to label antigen receptors on the surface of memory B cells and examined the frequency of antigen-specific CD19(+) CD27(+) memory B cells in the peripheral blood. sOP children showed a significantly lower percentage of antigen-specific CD19(+) CD27(+) memory B cells than NOP children. We also found a linear correlation between the frequencies of memory B cells and circulating IgG titres for DT, TT and PT proteins. To our knowledge, this is the first study to show significant differences in memory B cell responses to DTaP vaccine antigens and their correlation with the circulating antibodies in young children with recurrent AOM. PMID- 26138026 TI - Gene Expression of Lytic Endopeptidases AlpA and AlpB from Lysobacter sp. XL1 in Pseudomonads. AB - Development of an efficient expression system for (especially secreted) bacterial lytic enzymes is a complicated task due to the specificity of their action. The substrate for such enzymes is peptidoglycan, the main structural component of bacterial cell walls. For this reason, expression of recombinant lytic proteins is often accompanied with lysis of the producing bacterium. This paper presents data on the construction of an inducible system for expression of the lytic peptidases AlpA and AlpB from Lysobacter sp. XL1 in Pseudomonas fluorescens Q2 87, which provides for the successful secretion of these proteins into the culture liquid. In this system, the endopeptidase gene under control of the T7lac promoter was integrated into the bacterial chromosome, as well as the Escherichia coli lactose operon repressor protein gene. The T7 pol gene under lac promoter control, which encodes the phage T7 RNA polymerase, is maintained in Pseudomonas cells on the plasmids. Media and cultivation conditions for the recombinant strains were selected to enable the production of AlpA and AlpB by a simple purification protocol. Production of recombinant lytic enzymes should contribute to the development of new-generation antimicrobial drugs whose application will not be accompanied by selection of resistant microorganisms. PMID- 26138027 TI - Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression. AB - BACKGROUND: Neurogenesis continues throughout life in the hippocampal dentate gyrus. Chronic treatment with monoaminergic antidepressant drugs stimulates hippocampal neurogenesis, and new neurons are required for some antidepressant like behaviors. Electroconvulsive seizures (ECS), a laboratory model of electroconvulsive therapy (ECT), robustly stimulate hippocampal neurogenesis. HYPOTHESIS: ECS requires newborn neurons to improve behavioral deficits in a mouse neuroendocrine model of depression. METHODS: We utilized immunohistochemistry for doublecortin (DCX), a marker of migrating neuroblasts, to assess the impact of Sham or ECS treatments (1 treatment per day, 7 treatments over 15 days) on hippocampal neurogenesis in animals receiving 6 weeks of either vehicle or chronic corticosterone (CORT) treatment in the drinking water. We conducted tests of anxiety- and depressive-like behavior to investigate the ability of ECS to reverse CORT-induced behavioral deficits. We also determined whether adult neurons are required for the effects of ECS. For these studies we utilized a pharmacogenetic model (hGFAPtk) to conditionally ablate adult born neurons. We then evaluated behavioral indices of depression after Sham or ECS treatments in CORT-treated wild-type animals and CORT-treated animals lacking neurogenesis. RESULTS: ECS is able to rescue CORT-induced behavioral deficits in indices of anxiety- and depressive-like behavior. ECS increases both the number and dendritic complexity of adult-born migrating neuroblasts. The ability of ECS to promote antidepressant-like behavior is blocked in mice lacking adult neurogenesis. CONCLUSION: ECS ameliorates a number of anxiety- and depressive like behaviors caused by chronic exposure to CORT. ECS requires intact hippocampal neurogenesis for its efficacy in these behavioral indices. PMID- 26138029 TI - One-pot Unsymmetrical Ketone Synthesis Employing a Pyrrole-Bearing Formal Carbonyl Dication Linchpin Reagent. AB - A one-pot procedure for the synthesis of unsymmetrical ketones utilizing a pyrrole-bearing carbonyl linchpin reagent (carbonyl linchpin N,O dimethylhydroxylamine pyrrole; CLAmP) is reported. In contrast to other carbonyl dielectrophile equivalents, CLAmP enables the synthesis of ketones from a variety of organolithium and Grignard reagents. The electrophilic nature of CLAmP enables the addition of less reactive as well as thermally unstable nucleophiles. CLAmP was designed to form kinetically stable tetrahedral intermediates upon the addition of organometallic nucleophiles. Evidence for the existence of persistent tetrahedral intermediates was obtained through in situ IR studies. PMID- 26138028 TI - The Photoparoxysmal Response Reflects Abnormal Early Visuomotor Integration in the Human Motor Cortex. AB - BACKGROUND: Visual-paired associative stimulation (V-PAS) is a transcranial magnetic stimulation (TMS) technique able to investigate long-term potentiation (LTP) and depression (LTD)-like plasticity in the primary motor cortex (M1) arising through early visuomotor integration. OBJECTIVE/HYPOTHESIS: Abnormal early visuomotor integration might contribute to the pathophysiology of intermittent photic stimulation (IPS)-induced photoparoxysmal response (PPR). METHODS: We applied V-PAS in 25 healthy subjects (HS), 25 PPR-positive patients, with and without idiopathic generalized epilepsy (IGE), and 8 PPR-negative patients with IGE. V-PAS consisted of primary visual area activation achieved by visual evoked potentials coupled with TMS-induced M1 activation at 100 ms interstimulus interval (ISI) (V-PAS100). Before and after V-PAS, we measured changes in motor evoked potentials (MEPs). We compared MEPs after 1 Hz repetitive TMS (rTMS) and 0.25 Hz-V-PAS100. To examine possible V-PAS-induced after-effects at other ISIs, we delivered V-PAS at 40 (V-PAS40) and 140 ms ISIs (V-PAS140). To clarify whether V-PAS100 increases parieto-/premotor-to-M1 connectivity, before and after V-PAS100, we examined MEPs evoked by paired-pulse techniques. RESULTS: V-PAS100 increased MEPs more in PPR-positive patients than in HS. PPR-negative patients had normal response to V-PAS100. 1 Hz-rTMS, 0.25 Hz-V-PAS100 and V-PAS40 elicited similar responses in HS and PPR-positive patients, whereas V-PAS140 induced stronger after-effects in PPR-positive patients than HS. After V-PAS, MEPs elicited by facilitatory paired-pulse protocols decreased similarly in HS and PPR-positive patients. Conversely, MEPs elicited by inhibitory protocols decreased in HS, whereas in PPR-positive patients, they turned from inhibition to facilitation. CONCLUSION: We suggest that abnormal early visuomotor integration contributes to the pathophysiology of PPR. PMID- 26138030 TI - BMP2 Is Associated with Caries Experience in Primary Teeth. AB - Bone morphogenetic proteins (BMPs) play an important role during the initial process of enamel development and therefore may play a role in caries susceptibility. The purpose of this study was to evaluate the association between the polymorphisms in the BMP2, BMP4 and BMP7 genes and their association with caries experience and primary enamel microhardness characteristics. DNA from buccal cells as well as clinical and demographic information from 1,731 subjects from three different data sets from Brazil were included. Polymorphisms in BMP2, BMP4 and BMP7 were analyzed by real-time polymerase chain reaction from genomic DNA. Association between caries experience, genotype, and allele distribution in both cohorts was evaluated using chi(2) and logistic regression analyses. In the family-based set, the association between caries experience and alleles was tested using the transmission disequilibrium test. In the Rio de Janeiro cohort, microhardness data on 108 exfoliated primary teeth before and after demineralization and remineralization challenges was included. Associations between microhardness values and genotype and allele distribution were evaluated using chi(2) and logistic regression analyses. Differences between caries experience and some risk factors were statistically significant. In the cohort from Nova Friburgo, BMP2 was associated with caries experience in primary dentition during logistic regression analysis (p = 0.023; OR = 2.58; 95% CI 1.13 5.86). There was no association between genotype and allele distribution for BMP polymorphisms and primary enamel microhardness alterations. Our result suggests that BMP2 may be involved in caries experience in primary dentition from a Nova Friburgo cohort. PMID- 26138031 TI - Edge-terminated molybdenum disulfide with a 9.4-A interlayer spacing for electrochemical hydrogen production. AB - Layered molybdenum disulfide has demonstrated great promise as a low-cost alternative to platinum-based catalysts for electrochemical hydrogen production from water. Research effort on this material has focused mainly on synthesizing highly nanostructured molybdenum disulfide that allows the exposure of a large fraction of active edge sites. Here we report a promising microwave-assisted strategy for the synthesis of narrow molybdenum disulfide nanosheets with edge terminated structure and a significantly expanded interlayer spacing, which exhibit striking kinetic metrics with onset potential of -103 mV, Tafel slope of 49 mV per decade and exchange current density of 9.62 * 10(-3) mA cm(-2), performing among the best of current molybdenum disulfide catalysts. Besides benefits from the edge-terminated structure, the expanded interlayer distance with modified electronic structure is also responsible for the observed catalytic improvement, which suggests a potential way to design newly advanced molybdenum disulfide catalysts through modulating the interlayer distance. PMID- 26138032 TI - Organ Procurement Organizations and the Electronic Health Record. AB - The adoption of electronic health records (EHRs) has adversely affected the ability of organ procurement organizations (OPOs) to perform their federally mandated function of honoring the donation decisions of families and donors who have signed the registry. The difficulties gaining access to potential donor medical record has meant that assessment, evaluation, and management of brain dead organ donors has become much more difficult. Delays can occur that can lead to potential recipients not receiving life-saving organs. For over 40 years, OPO personnel have had ready access to paper medical records. But the widespread adoption of EHRs has greatly limited the ability of OPO coordinators to readily gain access to patient medical records and to manage brain dead donors. Proposed solutions include the following: (1) hospitals could provide limited access to OPO personnel so that they could see only the potential donor's medical record; (2) OPOs could join with other transplant organizations to inform regulators of the problem; and (3) hospital organizations could be approached to work with Center for Medicare and Medicaid Services (CMS) to revise the Hospital Conditions of Participation to require OPOs be given access to donor medical records. PMID- 26138033 TI - Sensory initiation of a co-ordinated motor response: synaptic excitation underlying simple decision-making. AB - KEY POINTS: Deciding whether or how to initiate a motor response to a stimulus can be surprisingly slow and the underlying processes are not well understood. The neuronal circuitry that allows frog tadpoles to swim in response to touch is well characterized and includes excitatory reticulospinal neurons that drive swim circuit neurons. Build-up of excitation to reticulospinal neurons is the key decision-making step for swimming. Asymmetry in this build-up between the two sides allows bilateral initiation at the same time as avoiding inappropriate co activation of motor antagonists. Following stronger stimuli, reticulospinal neurons are excited through a trigeminal nucleus pathway and swimming starts first on the stimulated side. If this pathway fails or is lesioned, swimming starts later on the unstimulated side. The mechanisms underlying initiation of a simple tadpole motor response may share similarities with more complex decisions in other animals, including humans. ABSTRACT: Animals take time to make co ordinated motor responses to a stimulus. How can sensory input initiate organized movements, activating all necessary elements at the same time as avoiding inappropriate co-excitation of antagonistic muscles? In vertebrates, this process usually results in the activation of reticulospinal pathways. Young Xenopus tadpoles can respond to head-skin touch by swimming, which may start on either side. We investigate how motor networks in the brain are organized, and whether asymmetries in touch sensory pathways avoid co-activation of antagonists at the same time as producing co-ordinated movements. We record from key reticulospinal neurons in the network controlling swimming. When the head skin is stimulated unilaterally, excitation builds up slowly and asymmetrically in these neurons such that those on both sides do not fire synchronously. This build-up of excitation to threshold is the key decision-making step and determines whether swimming will start, as well as on which side. In response to stronger stimuli, the stimulated side tends to 'win' because excitation from a shorter, trigeminal nucleus pathway becomes reliable and can initiate swimming earlier on the stimulated side. When this pathway fails or is lesioned, swimming starts later and on the unstimulated side. Stochasticity in the trigeminal nucleus pathway allows unpredictable turning behaviour to weaker stimuli, conferring potential survival benefits. We locate the longer, commissural sensory pathway carrying excitation to the unstimulated side and record from its neurons. These neurons fire to head-skin stimuli but excite reticulospinal neurons indirectly. We propose that asymmetries in the sensory pathways exciting brainstem reticulospinal neurons ensure alternating and co-ordinated swimming activity from the start. PMID- 26138034 TI - Vertical twinning of the Dirac cone at the interface between topological insulators and semiconductors. AB - Topological insulators are a new class of matter characterized by the unique electronic properties of an insulating bulk and metallic boundaries arising from non-trivial bulk band topology. While the surfaces of topological insulators have been well studied, the interface between topological insulators and semiconductors may not only be more technologically relevant, but the interaction with non-topological states may fundamentally alter the physics. Here, we present a general model to show that this type of interaction can lead to vertical twinning of the Dirac cone, whereby the hybridized non-spin-degenerate interfacial states cross twice as they span the bulk bandgap. This hybridization leads to spin-momentum locking of non-topological states with either helical (clockwise or anticlockwise) or even anti-helical (negative winding number) spin orientation depending on the parametization of the interaction. Model results are corroborated by first-principles calculations of the technologically relevant Bi2Se3 film van der Waals bound to a Se-treated GaAs substrate. PMID- 26138035 TI - Pathogenetic Implications of BRAF Mutation Distribution in Stage IV Melanoma Patients. AB - BACKGROUND: BRAF mutation frequencies in melanoma subtypes have clinical implications and offer pathogenetic clues. OBJECTIVES: To characterize BRAF mutation status in melanoma of unknown primary (MUP) patients, in histological melanoma subtypes and by localization of primary tumors. METHODS: In 179 patients with stage IV metastatic melanoma, BRAF mutation status, histological subtype and localization of primary (except for 29 MUP patients) were analyzed. RESULTS: BRAF mutations were found in 44.3%, of which 80.5% were BRAF V600E and 19.5% showed non-V600E BRAF mutations. BRAF mutation frequency depended on histological subtype (57.4% superficial spreading melanoma, 54.7% nodular melanoma, 11.1% mucosal melanoma, 28.6% acral lentiginous melanoma) and concerning non-V600E BRAF mutations on localization of primary. In MUP the BRAF mutation pattern resembled superficial spreading and nodular melanomas. CONCLUSION: BRAF mutation frequencies depend on histological subtype and localization of primary melanoma. Non-V600E BRAF mutations mostly occur in patients with primaries on 'head and neck' as well as 'trunk' but not on 'extremities'. PMID- 26138036 TI - CER Hub: An informatics platform for conducting comparative effectiveness research using multi-institutional, heterogeneous, electronic clinical data. AB - OBJECTIVES: Comparative effectiveness research (CER) requires the capture and analysis of data from disparate sources, often from a variety of institutions with diverse electronic health record (EHR) implementations. In this paper we describe the CER Hub, a web-based informatics platform for developing and conducting research studies that combine comprehensive electronic clinical data from multiple health care organizations. METHODS: The CER Hub platform implements a data processing pipeline that employs informatics standards for data representation and web-based tools for developing study-specific data processing applications, providing standardized access to the patient-centric electronic health record (EHR) across organizations. RESULTS: The CER Hub is being used to conduct two CER studies utilizing data from six geographically distributed and demographically diverse health systems. These foundational studies address the effectiveness of medications for controlling asthma and the effectiveness of smoking cessation services delivered in primary care. DISCUSSION: The CER Hub includes four key capabilities: the ability to process and analyze both free-text and coded clinical data in the EHR; a data processing environment supported by distributed data and study governance processes; a clinical data-interchange format for facilitating standardized extraction of clinical data from EHRs; and a library of shareable clinical data processing applications. CONCLUSION: CER requires coordinated and scalable methods for extracting, aggregating, and analyzing complex, multi-institutional clinical data. By offering a range of informatics tools integrated into a framework for conducting studies using EHR data, the CER Hub provides a solution to the challenges of multi-institutional research using electronic medical record data. PMID- 26138038 TI - Re: K. Hatzimouratidis, I. Eardley, F. Giuliano, I. Moncada, A. Salonia. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. European Association of Urology Web site. http://uroweb.org/guideline/male-sexual-dysfunction/. Updated 2015. PMID- 26138037 TI - Carbonic anhydrase IX as a diagnostic urinary marker for urothelial bladder cancer. AB - Urinary biomarkers are needed to improve the management and reduce the cost of urothelial bladder cancer (UBC); however, none have been recommended yet for clinical practice. This study evaluated carbonic anhydrase IX (CAIX) as a diagnostic urinary biomarker for UBC. CAIX was analyzed by quantitative polymerase chain reaction in urine samples of 196 patients with UBC and 123 controls with hematuria. Paired samples from urine and tumor tissue were evaluated in 16 cases. Data were validated in 155 independent samples. The sensitivity and specificity of CAIX for UBC detection were 86.2% and 95.1%, respectively (area under the curve [AUC]: 90.5%). There was a significant association of CAIX expression between the paired urine and tumor specimens (p=0.002). CAIX showed a significantly higher predictive accuracy than urinary cytology (90.5% vs 71.7%), specifically in low-grade tumors (90.0% vs 61.8%). CAIX expression decreased with increasing tumor stage and grade. Analyses in an independent validation cohort confirmed the high accuracy of CAIX for diagnosing UBC (AUC: 88.3%). PATIENT SUMMARY: We evaluated carbonic anhydrase IX (CAIX) as a urinary marker for bladder cancer (BCa) using a large series of patients from a single hospital. We found that urinary CAIX has a high sensitivity and specificity for diagnosing BCa. PMID- 26138039 TI - Reply to Pero Bokarica's letter to the editor re: K. Hatzimouratidis, I. Eardley, F. Giuliano, I. Moncada, A. Salonia. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. European Association of Urology Website. http://uroweb.org/guideline/male-sexual-dysfunction/. Updated 2015. PMID- 26138040 TI - Androgen Deprivation Therapy for Prostate Cancer and the Risk of Venous Thromboembolism. AB - BACKGROUND: Few observational studies have investigated the association between androgen deprivation therapy (ADT) and venous thromboembolism (VTE) in patients with prostate cancer (PCa). OBJECTIVE: To determine whether the use of different types of ADT in patients with PCa is associated with an increased incidence of VTE. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study was conducted using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of men newly diagnosed with PCa between April 1, 1998, and March 31, 2014. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Cox proportional hazards models with a time-varying exposure definition were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of patients hospitalized for VTE associated with current and past ADT use compared with nonuse. A secondary analysis was conducted to assess the risk with current use of specific types of ADT. RESULTS AND LIMITATIONS: The cohort included 21 729 patients, of whom 609 were hospitalized for VTE during follow-up. Current ADT use was associated with an 84% increased risk of VTE (incidence rates: 10.1 vs 4.8 per 1000 person-years; HR: 1.84; 95% CI, 1.50-2.26), whereas there was no association with past use (HR: 1.07; 95% CI, 0.81-1.42). In the secondary analysis, most types of ADT were associated with a high risk of VTE. Residual confounding is possible given the observational nature of the study. CONCLUSIONS: The use of ADT was associated with an overall 84% increased risk of VTE, with the risk elevated for most ADT types. PATIENT SUMMARY: In this study, we investigated whether androgen deprivation therapy was associated with the risk of blood clots in a cohort of patients with prostate cancer. We observed that the risk was nearly doubled in patients who used ADT compared with those who never used it. This treatment should be reserved for patients for whom the benefits outweigh the risks. PMID- 26138041 TI - Immediate versus delayed radical prostatectomy: updated outcomes following active surveillance of prostate cancer. AB - BACKGROUND: Biopsy progression on active surveillance (AS) for prostate cancer (PCa) often reflects failure of the initial biopsy to detect cancer present at enrollment. The risks for delayed treatment among men who progress on AS are not well defined. OBJECTIVE: To report outcomes for men who underwent surgery after AS compared to men who underwent immediate surgery and the influence of selection bias on this outcome. DESIGN, SETTING, AND PARTICIPANTS: AS-eligible (ASE) men who underwent radical prostatectomy (RP) after a median of 20 mo of AS were compared to ASE men who underwent RP within 6 mo of diagnosis. A subset of men on AS who underwent RP after upgrade to Gleason 3+4 was compared to matched controls with similar pretreatment biopsy features who underwent immediate RP. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Rates of adverse pathology (upstaging, positive surgical margin, or Gleason upgrading) were examined. Logistic regression was used to determine associations between treatment subgroup and adverse pathology. RESULTS AND LIMITATIONS: Of 157 ASE men who underwent delayed RP after AS, 54 were upgraded to Gleason 3+4 before surgery. ASE men who underwent immediate RP had lower probability of adverse pathology than ASE men who underwent delayed RP (hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.21-0.55). The rate of adverse pathology did not differ between immediate and delayed RP patients matched for pretreatment characteristics (HR 0.79, 95% CI 0.27-2.28). The observational design of this study is its main limitation. CONCLUSIONS: When compared to men with similar pretreatment biopsy features, those who underwent delayed RP were not at higher risk of adverse pathology. PATIENT SUMMARY: The oncologic safety of delayed treatment when indicated for men enrolled in active surveillance for prostate cancer is important. We found that men who underwent delayed surgery had similar outcomes to men who underwent immediate prostatectomy. PMID- 26138042 TI - Treatment of the Primary Tumour in the Presence of Metastases: Lessons from Breast Cancer. PMID- 26138043 TI - Compliance Rates with the Prostate Cancer Research International Active Surveillance (PRIAS) Protocol and Disease Reclassification in Noncompliers. AB - BACKGROUND: Men with prostate cancer on active surveillance (AS) are advised to follow strict follow-up schedules and switch to definitive treatment on risk reclassification. However, some men might not adhere to these strict protocols. OBJECTIVE: To determine the number of noncompliers and disease reclassification rates in men not complying with the follow-up protocol of the Prostate Cancer Research International Active Surveillance (PRIAS) study. DESIGN, SETTING, AND PARTICIPANTS: A total of 4547 men with low-risk prostate cancer were included and prospectively followed on AS. Men were regularly examined using prostate-specific antigen (PSA), digital rectal examination, and repeat biopsies, and were advised to switch to definitive treatment on disease reclassification (>cT2c, Gleason score > 3+3, >2 cores positive, or PSA doubling time [PSA-DT] 0-3 yr). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rates of men not complying with follow-up visits or a recommendation to discontinue AS are reported. Biopsy outcome (Gleason >=7 or >2 cores positive) was compared between compliers and noncompliers using Cox proportional hazards analysis. RESULTS AND LIMITATIONS: The compliance rate for PSA visits was 91%. By contrast, the compliance rate for standard repeat biopsies decreased over time (81%, 60%, 53%, and 33% at 1, 4, 7, and 10 yr after diagnosis, respectively). Yearly repeat biopsies in men with faster rising PSA (PSA-DT 3-10 yr) was low at <30%, although these men had higher upgrading rates at repeat biopsy (25-30% vs 16%). PSA-DT of 0-3 yr was the most common recommendation for discontinuation, but 71% continued on AS. Men with PSA DT of 0-3 yr were at higher risk of upgrading on repeat biopsy (hazard ratio 2.02, 95% confidence interval 1.36-3.00) compared to men without fast rising PSA. CONCLUSION: Some men and their physicians do not comply with AS follow-up protocols. In particular, yearly repeat biopsies in men with fast rising PSA are often ignored, as is the recommendation to discontinue AS because of very fast rising PSA. Although these men are at greater risk of higher Gleason scores on repeat biopsy, the majority still exhibit favorable tumor characteristics. Fast rising PSA should therefore not trigger a recommendation to receive active treatment, but should rather serve as a criterion for stricter follow-up. In addition, we should aim to find ways of safely reducing the number of biopsies to increase adherence to AS protocols. PATIENT SUMMARY: We looked at compliance with an active surveillance protocol for low-risk prostate cancer in a large active surveillance study. We observed reluctance to undergo yearly biopsies because of fast rising prostate-specific antigen, despite a higher risk of disease progression. Further research should aim to safely reduce the number of repeat biopsies in men on active surveillance to increase protocol adherence. PMID- 26138044 TI - Tobacco-free homes for tobacco-free generations: establishing positive smoke-free role models for youth. PMID- 26138045 TI - Emotional regulation of mental pain as moderator of suicidal ideation in military settings. AB - BACKGROUND: In the Israel Defense Forces (IDF) as well as in most armies throughout the world, the leading cause of death during peace-time is suicide. This study examines emotional regulation of mental pain as a contributor to suicidal ideation in soldiers. METHODS: One hundred sixty-eight IDF soldiers (aged 18-21years, 59% males) completed the following self-report questionnaires: Scale for Suicide Ideation (SSI); Orbach & Mikulincer Mental Pain Scale (OMMP); and Emotional Regulation of Mental Pain questionnaire. Participants were divided into 3 groups: soldiers who attempted suicide (AS group, n=58), soldiers under treatment by a mental health professional and reporting no suicidal behavior (PT group, n=58), and controls (C group, n=50). RESULTS: Suicide ideation, mental pain, and low emotional regulation were significantly higher in the suicidal group as compared to the two other groups (P<0.001). Mental pain was significantly related to more suicide ideation in soldiers with low ability to regulate mental pain (P<.001 for the interaction). CONCLUSION: Emotional regulation of mental pain moderates the link between mental pain and suicide ideation. Soldiers with high mental pain and low regulation of mental pain exhibited higher suicidal ideation. These findings may assist in planning prevention programs in the army and similar settings. PMID- 26138046 TI - Three-dimensional structure of cyclic antibiotic teicoplanin aglycone using NMR distance and dihedral angle restraints in a DMSO solvation model. AB - The three-dimensional solution conformation of teicoplanin aglycone was determined using NMR spectroscopy. A combination of NOE and dihedral angle restraints in a DMSO solvation model was used to calculate an ensemble of structures having a root mean square deviation of 0.17 A. The structures were generated using systematic searches of conformational space for optimal satisfaction of distance and dihedral angle restraints. Comparison of the NMR derived structure of teicoplanin aglycone with the X-ray structure of a teicoplanin aglycone analog revealed a common backbone conformation with deviation of two aromatic side chain substituents. Experimentally determined backbone (13)C chemical shifts showed good agreement with those computed at the density functional level of theory, providing a cross validation of the backbone conformation. The flexible portion of the molecule was consistent with the region that changes conformation to accommodate protein binding. The results showed that a hydrogen-bonded DMSO molecule in combination with NMR-derived restraints together enabled calculation of structures that satisfied experimental data. PMID- 26138047 TI - Bacterial diversity and composition in the fluid of pitcher plants of the genus Nepenthes. AB - Pitchers are modified leaves used by carnivorous plants for trapping prey. Their fluids contain digestive enzymes from the plant and they harbor abundant microbes. In this study, the diversity of bacterial communities was assessed in Nepenthes pitcher fluids and the composition of the bacterial community was compared to that in other environments, including the phyllosphere of Arabidopsis, animal guts and another pitcher plant, Sarracenia. Diversity was measured by 454 pyrosequencing of 16S rRNA gene amplicons. A total of 232,823 sequences were obtained after chimera and singleton removal that clustered into 3260 distinct operational taxonomic units (OTUs) (3% dissimilarity), which were taxonomically distributed over 17 phyla, 25 classes, 45 orders, 100 families, and 195 genera. Pyrosequencing and fluorescence in situ hybridization yielded similar estimates of community composition. Most pitchers contained high proportions of unique OTUs, and only 22 OTUs (<0.6%) were shared by >=14/16 samples, suggesting a unique bacterial assemblage in each pitcher at the OTU level. Diversity analysis at the class level revealed that the bacterial communities of both opened and unopened pitchers were most similar to that of Sarracenia and to that in the phyllosphere. Therefore, the bacterial community in pitchers may be formed by environmental filtering and/or by phyllosphere bacteria. PMID- 26138048 TI - Efficient high-throughput biological process characterization: Definitive screening design with the ambr250 bioreactor system. AB - The burgeoning pipeline for new biologic drugs has increased the need for high throughput process characterization to efficiently use process development resources. Breakthroughs in highly automated and parallelized upstream process development have led to technologies such as the 250-mL automated mini bioreactor (ambr250TM) system. Furthermore, developments in modern design of experiments (DoE) have promoted the use of definitive screening design (DSD) as an efficient method to combine factor screening and characterization. Here we utilize the 24 bioreactor ambr250TM system with 10-factor DSD to demonstrate a systematic experimental workflow to efficiently characterize an Escherichia coli (E. coli) fermentation process for recombinant protein production. The generated process model is further validated by laboratory-scale experiments and shows how the strategy is useful for quality by design (QbD) approaches to control strategies for late-stage characterization. PMID- 26138049 TI - The importance of retesting the hearing screening as an indicator of the real early hearing disorder. AB - INTRODUCTION: Early diagnosis of hearing loss minimizes its impact on child development. We studied factors that influence the effectiveness of screening programs. OBJECTIVE: To investigate the relationship between gender, weight at birth, gestational age, risk factors for hearing loss, venue for newborn hearing screening and "pass" and "fail" results in the retest. METHODS: Prospective cohort study was carried out in a tertiary referral hospital. The screening was performed in 565 newborns through transient evoked otoacoustic emissions in three admission units before hospital discharge and retest in the outpatient clinic. Gender, weight at birth, gestational age, presence of risk indicators for hearing loss and venue for newborn hearing screening were considered. RESULTS: Full-term infants comprised 86% of the cases, preterm 14%, and risk factors for hearing loss were identified in 11%. Considering the 165 newborns retested, only the venue for screening, Intermediate Care Unit, was related to "fail" result in the retest. CONCLUSIONS: Gender, weight at birth, gestational age and presence of risk factors for hearing loss were not related to "pass" and/or "fail" results in the retest. The screening performed in intermediate care units increases the chance of continued "fail" result in the Transient Otoacoustic Evoked Emissions test. PMID- 26138050 TI - Epidemiology of communication disorders in childhood phoniatric clinical practice. AB - INTRODUCTION: Language acquisition and development require an understanding of physical and psychosocial aspects during diagnosis and treatment. At this point, a partnership between phoniatric physicians and other health professionals is often a determinant for favorable prognosis. OBJECTIVE: To identify the clinical and epidemiological characteristics of a pediatric population attending a phoniatric clinical practice. METHODS: STUDY DESIGN: Cross-sectional cohort. Retrospective, epidemiological study of 297 children, seen in phoniatric appointments between 1976 and 2005. Outcome variables were referral origin, gender, age, mean age, diagnosis, and treatment approach. RESULTS: 66% were male and 34% were female, with a mean age of 6.4 years. The largest number of referrals for phoniatric treatments came from speech therapists (38%). The predominant complaint was alteration in speech (35%); the diagnostics in speech, language, and fluency (49.5%) are noteworthy. Considering the total of the patients analyzed, 28.2% were referred for speech therapy and 11.8% for psychotherapy. CONCLUSION: The studied population is predominantly male, the diagnosis points to a higher incidence in cases of impairment in speech, language, and fluency; the most common treatment was speech therapy. PMID- 26138051 TI - Prognostic impact of molecular phenotype in patients with recurrent anaplastic glioma treated with prolonged administration of temozolomide. AB - We retrospectively investigated the prognostic impact of molecular phenotypes in patients with recurrent anaplastic glioma treated with prolonged administration of temozolomide (TMZ). Malignant gliomas have a dismal prognosis despite the available multimodal treatments. We reviewed 87 patients who were diagnosed with recurrent anaplastic gliomas between March 2004 and June 2010, and 58 were enrolled for analysis. In the cohort, 21 patients had anaplastic oligodendrogliomas, 18 anaplastic oligoastrocytomas and 19 anaplastic astrocytomas. All patients were initially treated with surgical resection or biopsy followed by involved-field radiotherapy. At recurrence, patients were treated with 150-200mg/m(2) of TMZ on days 1-5 in 28 day cycles until disease progression. We evaluated the association of molecular phenotypes, including 1p19q deletion, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, isocitrate dehydrogenase-1 (IDH1) mutation and other clinico histopathological findings with treatment outcome. During the mean follow-up period of 34.6 months, 33 patients were still alive (56.9%). Median survival from recurrence was 39.7 months (95% confidence interval [CI] 22.7-56.7). Time to progression from administration of TMZ was 6.4 months (95% CI 5.0-7.8). Univariate analysis demonstrated that the presence of the IDH1 mutation was closely associated with treatment response (8.4 versus 3.8 months; p=0.015). Oligodendroglial lineage, 1p19q deletion status and MGMT promoter methylation status were not independent variables for determining the TMZ treatment outcome. In recurrent anaplastic gliomas, TMZ treatment is an effective modality regardless of MGMT methylation status or histological type. The IDH1 mutation has the most powerful prognostic impact on overall patient survival. PMID- 26138053 TI - Editorial Comment on: Changes in Autonomic Nervous System Activity are Associated with Changes in Sexual Function in Women with a History of Childhood Sexual Abuse. PMID- 26138052 TI - Extreme lateral interbody fusion with posterior instrumentation for spondylodiscitis. AB - The purpose of this study was to evaluate our initial experience utilizing extreme lateral interbody fusion (XLIF; NuVasive, San Diego, CA, USA) with percutaneous posterior instrumentation to treat 11 spondylodiscitis patients between January 2011 and February 2014. Although medical management is the first line treatment for spondylodiscitis, many patients fail antibiotic therapy and bracing, or present with instability, neurologic deficits, or sepsis, requiring operative debridement and stabilization. High rates of fusion and infection clearance have been reported with anterior lumbar interbody fusion (ALIF), but this approach requires a morbid exposure, associated with non-trivial rates of vascular and peritoneal complications. XLIF is an increasingly popular interbody fusion technique which utilizes a fast and minimally invasive approach, sparing the anterior longitudinal ligament, and allowing sufficient visualization of the intervertebral discs and bodies to debride and place a large, lordotic cage. The outcome measures for this study included lumbar lordosis, sagittal balance, subsidence, fusion, pain, neurological deficit, and microbiology/laboratory evidence of infection. The mean follow-up time was 9.3 months. All patients had improvements in pain and neurological symptoms. The mean lordosis change was 11.0 degrees , from 23.1 degrees preoperatively to 34.0 degrees postoperatively. Fusion was confirmed with CT scans in five of six patients. At the last follow up, all patients had normalization of inflammatory markers, no symptoms of infection, and none required repeat surgical treatment for spondylodiscitis. XLIF with percutaneous posterior instrumentation is a minimally invasive technique with reduced morbidity for lumbar spine fusion which affords adequate exposure to the vertebral bodies and discs to aggressively debride necrotic and infected tissue. This study suggests that XLIF may be a safe and effective alternative to ALIF for the treatment of spondylodiscitis. PMID- 26138054 TI - Magnetic resonance imaging findings of paracoccidioidomycosis in the musculoskeletal system. AB - OBJECTIVE: To describe magnetic resonance imaging (MRI) findings in musculoskeletal paracoccidioidomycosis (PCM). METHODS: Retrospective case series study after IRB approval. Two musculoskeletal radiologists reviewed in consensus the MRI findings of 11 patients with microbiologically and/or pathologically proven osteoarticular PCM. The MRI evaluation included discrimination of abnormalities in joints, bones and soft tissues. RESULTS: Mean age of patients was 29 years (10-55 years), eight men and three women. Musculoskeletal involvement was the only or the primary presentation of the disease in seven patients (63%). Osteomyelitis was the most common presentation, with seven cases (63%). Primary arthritis was found in one patient (9%). Isolated extra-articular soft tissue PCM was found in three patients: myositis (2) and subcutaneous infection (1). All cases showed regions with signal intensity higher than or similar to the signal of muscle on T1-weighted images. Penumbra sign was present in five cases (45%). T2-weighted images showed reactive soft tissue oedema in eight cases (72%). Post-gadolinium images showed peripheral (8/9) or heterogeneous (1/9) enhancement. Synovial enhancement was present in all cases of joint involvement (6/6). Lipomatosis arborescens was documented in one case of chronic knee involvement. CONCLUSION: To our knowledge, this is the first case series describing MRI findings of musculoskeletal PCM. Musculoskeletal involvement was the primary presentation of the disease in most cases, and therefore, neoplasms were initially in the differential diagnosis. Osteomyelitis was the most common presentation, often with secondary involvement of joint and or soft tissue. PMID- 26138055 TI - Reply: To PMID 25779102. PMID- 26138056 TI - Fournier's gangrene: a surgical emergency. PMID- 26138057 TI - Combination of radiotherapy with the immunocytokine L19-IL2: Additive effect in a NK cell dependent tumour model. AB - BACKGROUND AND PURPOSE: Recently, we have shown that radiotherapy (RT) combined with the immunocytokine L19-IL2 can induce long-lasting antitumour effects, dependent on ED-B expression and infiltration of cytotoxic T cells. On the other hand, in certain tumours, IL2 treatment can trigger a natural killer cell (NK) immune response. The aim of this study is to investigate the therapeutic effect of our combination therapy in the ED-B positive F9 teratocarcinoma model, lacking MHCI expression and known to be dependent on NK immune responses. MATERIAL AND METHODS: In syngeneic F9 tumour bearing 129/FvHsd mice tumour growth delay was evaluated after local tumour irradiation (10Gy) combined with systemic administration of L19-IL2. Immunological responses were investigated using flow cytometry. RESULTS: Tumour growth delay of L19-IL2 can be further improved by a single dose of RT administered before immunotherapy, but not during immunotherapy. Furthermore, treatment of L19-IL2 favours a NK response and lacks cytotoxic T cell tumour infiltrating immune cells, which may be explained by the absence of MHCI expression. CONCLUSION: An additive effect can be detected when the NK dependent F9 tumour model is treated with radiotherapy and L19-IL2 and therefore this combination could be useful in the absence of tumoural MHCI expression. PMID- 26138058 TI - Similar ex vivo expansion and post-irradiation regenerative potential of juvenile and aged salivary gland stem cells. AB - BACKGROUND AND PURPOSE: Salivary gland dysfunction is a major side effect of radiotherapy for head and neck cancer patients, which in the future might be salvaged by autologous adult salivary gland stem cell (SGSC) therapy. Since frail elderly patients may have decreased activity of SGSCs, we aimed to characterize the potential of aged SGSC-population in a murine model. MATERIALS AND METHODS: Salivary glands and salisphere-derived cells from young and old mice were tested for CD24 and CD29 stem cell marker expression using FACS. Moreover, in vitro expansion capability and in vivo regeneration potential upon post-irradiation transplantation of young and aged SGSCs were measured. RESULTS: An increase in CD24(hi)/CD29(hi) putative stem cells was detected in aged salivary glands albeit with a decrease in functional ability to form salispheres. However, the salispheres formed from aged mice salivary glands expressed CD24(hi)/CD29(hi) to the same extent as the ones from young mice. Moreover, following exposure to adequate growth conditions old and young SGSCs exhibited similar in vitro expansion- and in vivo regeneration potential. CONCLUSIONS: Aged SGSCs although reduced in number are in vitro indistinguishable from young SGSCs and could potentially be used to ameliorate age- or treatment related salivary gland dysfunction. PMID- 26138059 TI - Risk and timing of biochemical recurrence in pT3aN0/Nx prostate cancer with positive surgical margin - A multicenter study. AB - BACKGROUND AND PURPOSE: Positive surgical margins (PSM) after radical prostatectomy have been shown to be associated with impaired outcome. In pT3pN0 patients with PSM either immediate radiotherapy or clinical and biological monitoring followed by salvage radiotherapy is recommended by the latest guidelines of the European Association of Urology. MATERIALS AND METHODS: A retrospective, multicenter study of eight urological centers was conducted on 536 prostatectomy patients with pT3aN0/NxR1 tumors and no neoadjuvant/adjuvant therapy. A pathological re-review of all prostate specimens was performed. Association of clinical and pathological features with biochemical recurrence (BCR) was analyzed using univariate and multivariate analysis. RESULTS: With 48months median follow-up, BCR occurred in 39.7%. Preoperative PSA value, performance of pelvic lymph node dissection and Gleason score were significantly associated with BCR. In multivariate analysis, Gleason score was the only independent prognostic factor (p<0.001) for BCR. Five-year BCR-free survival rates were 74%, 70%, 38%, and 51% with Gleason score 6, 3+4=7a, 4+3=7b, and 8-10, respectively. CONCLUSIONS: In pT3aN0/NxR1 patients with no adjuvant/neoadjuvant treatment, Gleason Score permits independent prediction of the risk for BCR. These findings could help to estimate and discuss the individual risk for BCR with our patients on an individual basis. PMID- 26138060 TI - Bloodstream bacterial infection among outpatient children with acute febrile illness in north-eastern Tanzania. AB - BACKGROUND: Fever is a common clinical symptom in children attending hospital outpatient clinics in rural Tanzania, yet there is still a paucity of data on the burden of bloodstream bacterial infection among these patients. METHODS: The present study was conducted at Korogwe District Hospital in north-eastern Tanzania. Patients aged between 2 and 59 months with a history of fever or measured axillary temperature >=37.5 degrees C attending the outpatient clinic were screened for enrolment into the study. Blood culturing was performed using the BACTEC 9050(r) system. A biochemical analytical profile index and serological tests were used for identification and confirmation of bacterial isolates. In vitro antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method. The identification of Plasmodium falciparum malaria was performed by microscopy with Giemsa stained blood films. RESULTS: A total of 808 blood cultures were collected between January and October 2013. Bacterial growth was observed in 62/808 (7.7%) of the cultured samples. Pathogenic bacteria were identified in 26/808 (3.2%) cultures and the remaining 36/62 (58.1%) were classified as contaminants. Salmonella typhi was the predominant bacterial isolate detected in 17/26 (65.4%) patients of which 16/17 (94.1%) were from patients above 12 months of age. Streptococcus pneumoniae was the second leading bacterial isolate detected in 4/26 (15.4%) patients. A high proportion of S. typhi 11/17 (64.7%) was isolated during the rainy season. S. typhi isolates were susceptible to ciprofloxacin (n = 17/17, 100%) and ceftriaxone (n = 13/17, 76.5%) but resistant to chloramphenicol (n = 15/17, 88.2%). P. falciparum malaria was identified in 69/808 (8.5%) patients, none of whom had bacterial infection. CONCLUSION: Bloodstream bacterial infection was not found to be a common cause of fever in outpatient children; and S. typhi was the predominant isolate. This study highlights the need for rational use of antimicrobial prescription in febrile paediatric outpatients presenting at healthcare facilities in rural Tanzania. PMID- 26138062 TI - Two Decades of Endovascular Repair of Popliteal Artery Aneurysm--A Meta-analysis. AB - OBJECTIVE/BACKGROUND: Over the last two decades endovascular repair (EVR) of popliteal artery aneurysms has emerged as a treatment alternative to conventional open surgical repair (OSR). The aim of this review was to evaluate the safety and efficiency of each repair method, comparing the following outcomes after EVR and OSR: (i) primary patency; (ii) operating time; (iii) length of hospital stay; (iv) peri-operative complications; (v) limb salvage; and (vi) patient survival. METHODS: The PubMed and Cochrane Central Register of Controlled Trials were searched for publications that compared outcomes after EVR and OSR (last search November 2014). Randomized controlled trials (RCTs), prospective and retrospective observational cohort studies were included. The quality of studies was evaluated using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Random effect models were employed to estimate odds ratios (ORs), mean differences, and hazard ratios (HRs). RESULTS: One RCT combined with a prospective cohort study and four retrospective cohort studies with an overall total of 652 cases (236 EVR, 416 OSR) were identified. GRADE quality of evidence was low or very low for all outcomes. After a median follow up of 33 months, patients who received EVR showed equal primary patency rates to patients who received OSR (HR 1.46, 95% confidence interval [CI] 0.92-2.33). Lengths of operation and hospitalization were significantly shorter following EVR; rates of 30 day graft thrombosis (OR 3.16, 95% CI 1.31-7.62) and 30 day re-intervention (OR 2.15, 95% CI 1.02-4.55) were significant higher for patients who received EVR compared with those who received OSR. There was no effect on mortality (OR 2.31, 95% CI 0.37-14.49) or limb loss (OR 0.59, 95% CI 0.16-2.15). CONCLUSION: EVR of popliteal artery aneurysm showed mid-term results comparable to open surgery and appears to be a safe alternative to OSR. However, the existing empirical evidence base is too fragmentary to draw firm conclusions. Further research and the introduction of population based registries will be needed to allow reliable evaluation of EVR. PMID- 26138061 TI - Low-molecular-mass secretome profiling identifies HMGA2 and MIF as prognostic biomarkers for oral cavity squamous cell carcinoma. AB - The profiling of cancer cell secretomes is considered to be a good strategy for identifying cancer-related biomarkers, but few studies have focused on identifying low-molecular-mass (LMr) proteins (<15 kDa) in cancer cell secretomes. Here, we used tricine-SDS-gel-assisted fractionation and LC-MS/MS to systemically identify LMr proteins in the secretomes of five oral cavity squamous cell carcinoma (OSCC) cell lines. Cross-matching of these results with nine OSCC tissue transcriptome datasets allowed us to identify 33 LMr genes/proteins that were highly upregulated in OSCC tissues and secreted/released from OSCC cells. Immunohistochemistry and quantitative real-time PCR were used to verify the overexpression of two candidates, HMGA2 and MIF, in OSCC tissues. The overexpressions of both proteins were associated with cervical metastasis, perineural invasion, deeper tumor invasion, higher overall stage, and a poorer prognosis for post-treatment survival. Functional assays further revealed that both proteins promoted the migration and invasion of OSCC cell lines in vitro. Collectively, our data indicate that the tricine-SDS-gel/LC-MS/MS approach can be used to efficiently identify LMr proteins from OSCC cell secretomes, and suggest that HMGA2 and MIF could be potential tissue biomarkers for OSCC. PMID- 26138063 TI - Folic acid supplementation, dietary folate intake and risk of preterm birth in China. AB - PURPOSE: Folic acid supplementation has been suggested to reduce the risk of preterm birth. However, results from previous epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake during pre- and post-conception reduces the risk of preterm birth. METHODS: We analyzed data from a birth cohort study conducted between 2010 and 2012 in Lanzhou, China, including 10,179 pregnant women with live singleton births. RESULTS: Compared to non-users, folic acid supplement users with >12-week duration had a reduced risk of preterm birth (OR 0.67, 95 % CI 0.55-0.83) with a significant dose-response relationship (P for trend = 0.01). A similar pattern was observed for spontaneous preterm birth. Stronger associations were seen for ever use of folic acid supplement and very preterm birth (OR 0.50, 95 % CI 0.36 0.69) and spontaneous very preterm birth (OR 0.42, 95 % CI 0.29-0.63). Dietary folate intake during preconception and pregnancy were also associated with reduced risk of preterm birth (OR 0.68, 95 % CI 0.56-0.83, OR 0.57, 95 % CI 0.47 0.70 for the highest quartiles, respectively), particularly for spontaneous very preterm (OR 0.41, 95 % CI 0.24-0.72, OR 0.26, 95 % CI 0.15-0.47 for the highest quartiles, respectively). There were also decreased risks of preterm birth observed per 10-ug increase in dietary folate intake, and similar associations were found after stratification by folic acid supplementation status. CONCLUSIONS: Our results suggest that folic acid supplementation and higher dietary folate intake during preconception and pregnancy reduces the risk of preterm birth, and the protective effect varies by preterm subtypes. PMID- 26138064 TI - Single- and repeat-dose toxicity of IDX14184, a nucleotide prodrug with antiviral activity for hepatitis C viral infection, in mice, rats, and monkeys. AB - The single- and repeat-dose toxicity profile of IDX14184, a novel guanosine nucleotide prodrug with antiviral activity against hepatitis C viral infection, was characterized following once daily oral administration for durations up to 13, 26, and 32 weeks in mouse, rat, and cynomolgus monkey, respectively. The heart, liver, kidney, skeletal muscles, and lower gastrointestinal tract (cecum, colon, and/or rectum) were identified as the primary toxicity targets in these nonclinical species. The mouse was relatively insensitive to IDX14184-induced cardiac toxicity and hepatotoxicity. The rat was very sensitive to IDX14184 induced skeletal muscle, liver, heart, and lower gastrointestinal tract toxicity but relatively insensitive to kidney toxicity. The monkey is a good animal species to detect IDX14184-induced toxicity in the cardiac and skeletal muscles, and in the liver and kidney, but not lower gastrointestinal tract toxicity. The toxicity profile of IDX14184 was most appropriately characterized in rats and monkeys. The conduct of a series of cardiac size and function assessments during a non-rodent toxicology study using echocardiography proved great utility in this work. IDX14184 clinical development was eventually terminated due to suboptimal efficacy and regulatory concerns on potential heart and kidney injury in patients, as seen with a different guanosine nucleotide prodrug, BMS-986094. PMID- 26138065 TI - Genome-Wide Association Studies for Taxane-Induced Peripheral Neuropathy in ECOG 5103 and ECOG-1199. AB - PURPOSE: Taxane-induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN. EXPERIMENTAL DESIGN: We performed a genome-wide association study (GWAS) in 3,431 patients from the phase III adjuvant breast cancer trial, ECOG-5103 to compare genotypes with TIPN. We performed candidate validation of top SNPs for TIPN in another phase III adjuvant breast cancer trial, ECOG-1199. RESULTS: When evaluating for grade 3-4 TIPN, 120 SNPs had a P value of <10(-4) from patients of European descent (EA) in ECOG-5103. Thirty candidate SNPs were subsequently tested in ECOG-1199 and SNP rs3125923 was found to be significantly associated with grade 3-4 TIPN (P = 1.7 * 10(-3); OR, 1.8). Race was also a major predictor of TIPN, with patients of African descent (AA) experiencing increased risk of grade 2-4 TIPN (HR, 2.1; P = 5.6 * 10(-16)) and grade 3-4 TIPN (HR, 2.6; P = 1.1 * 10(-11)) compared with others. An SNP in FCAMR, rs1856746, had a trend toward an association with grade 2-4 TIPN in AA patients from the GWAS in ECOG-5103 (OR, 5.5; P = 1.6 * 10(-7)). CONCLUSIONS: rs3125923 represents a validated SNP to predict grade 3-4 TIPN. Genetically determined AA race represents the most significant predictor of TIPN. PMID- 26138066 TI - Increased Expression of HER2, HER3, and HER2:HER3 Heterodimers in HPV-Positive HNSCC Using a Novel Proximity-Based Assay: Implications for Targeted Therapies. AB - PURPOSE: In other cancer types, HPV infection has been reported to coincide with overexpression of HER2 (ERBB2) and HER3 (ERBB3); however, the association between HER2 or HER3 expression and dimer formation in HNSCC has not been reported. Overexpression of HER2 and HER3 may contribute to resistance to EGFR inhibitors, including cetuximab, although the contribution of HPV in modulating cetuximab response remains unknown. Determination of heterodimerization of HER receptors is challenging and has not been reported in HNSCC. The present study aimed to determine the expression of HER proteins in HPV(+) versus HPV(-) HNSCC tumors using a proximity-based protein expression assay (VeraTag), and to determine the efficacy of HER-targeting agents in HPV(+) and HPV(-) HNSCC cell lines. EXPERIMENTAL DESIGN: Expression of total HER1, HER2, and HER3, p95HER2, p-HER3, HER1:HER1 homodimers, HER2:HER3 heterodimers, and the HER3-PI3K complex in 88 HNSCC was determined using VeraTag, including 33 baseline tumors from individuals treated in a trial including cetuximab. Inhibition of cell growth and protein activation with cetuximab and afatinib was compared in HPV(+) and HPV(-) cetuximab-resistant cell lines. RESULTS: Expression of total HER2, total HER3, HER2:HER3 heterodimers, and the HER3:PI3K complex were significantly elevated in HPV(+) HNSCC. Total EGFR was significantly increased in HPV(-) HNSCC where VeraTag assay results correlated with IHC. Afatinib significantly inhibited cell growth when compared with cetuximab in the HPV(+) and HPV(-) cetuximab-resistant HNSCC cell lines. CONCLUSIONS: These findings suggest that agents targeting multiple HER proteins may be effective in the setting of HPV(+) HNSCC and/or cetuximab resistance. PMID- 26138068 TI - A passive-flow microfluidic device for imaging latent HIV activation dynamics in single T cells. AB - Quantifying cell-to-cell variability in drug response dynamics is important when evaluating therapeutic efficacy. For example, optimizing latency reversing agents (LRAs) for use in a clinical "activate-and-kill" strategy to purge the latent HIV reservoir in patients requires minimizing heterogeneous viral activation dynamics. To evaluate how heterogeneity in latent HIV activation varies across a range of LRAs, we tracked drug-induced response dynamics in single cells via live cell imaging using a latent HIV-GFP reporter virus in a clonal Jurkat T cell line. To enable these studies in suspension cells, we designed a simple method to capture an array of single Jurkat T cells using a passive-flow microfluidic device. Our device, which does not require external pumps or tubing, can trap hundreds of cells within minutes with a high retention rate over 12 hours of imaging. Using this device, we quantified heterogeneity in viral activation stimulated by transcription factor (TF) activators and histone deacetylase (HDAC) inhibitors. Generally, TF activators resulted in both faster onset of viral activation and faster rates of production, while HDAC inhibitors resulted in more uniform onset times, but more heterogeneous rates of production. Finally, we demonstrated that while onset time of viral gene expression and rate of viral production together predict total HIV activation, rate and onset time were not correlated within the same individual cell, suggesting that these features are regulated independently. Overall, our results reveal drug-specific patterns of noisy HIV activation dynamics not previously identified in static single-cell assays, which may require consideration for the most effective activate-and-kill regime. PMID- 26138069 TI - Quantitative Metrics for Assessing Positional and Orientational Order in Colloidal Crystals. AB - Although there are numerous self-assembly techniques to prepare colloidal crystals, there is great variability in the methods used to characterize order and disorder in these materials. We assess different kinds of structural order from more than 70 two-dimensional microscopy images of colloidal crystals produced by many common methods, including spin-coating, dip-coating, convective assembly, electrophoretic assembly, and sedimentation. Our suite of analysis methods includes measures for both positional and orientational order. The benchmarks are two-dimensional lattices that we simulated with different degrees of controlled disorder. We find that translational measures are adequate for characterizing small deviations from perfect order, whereas orientational measures are more informative for polycrystalline and highly disordered crystals. Our analysis presents a unified strategy for comparing structural order among different colloidal crystals and establishes benchmarks for future studies. PMID- 26138067 TI - Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization study. AB - Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various cancers. These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common cancer types (breast, lung, colorectal, ovarian and prostate cancer, including subtypes) using data on 51 725 cases and 62 035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and cancer risk. The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P = 6.3 * 10(-15)), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P = 6.6 * 10(-6)). Under Mendelian randomization assumptions, the association estimate [odds ratio (OR) = 2.78] is interpreted as the OR for lung adenocarcinoma corresponding to a 1000 bp increase in TL. The weighted TL SNP score was not associated with other cancer types or subtypes. Our finding that genetic determinants of long TL increase lung adenocarcinoma risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL increases lung adenocarcinoma risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk. PMID- 26138070 TI - Current status of preoperative biliary drainage. AB - Preoperative biliary drainage (PBD) has been thought to be preferable regardless of the site of biliary strictures, e.g., distal or proximal strictures because PBD by endoscopy or interventional radiology decreases postoperative mortality and morbidity rates. However, recently, several studies have revealed that PBD strategy showed an increased mortality rate or a high frequency of surgical site infection. Herein, we reviewed reports in the literature regarding the current status of PBD and investigated the effects of PBD on patients with distal and proximal biliary obstructions due to potentially resectable pancreatobiliary cancers. Our summary demonstrated that there is as yet no optimal PBD method regardless of the distal and proximal biliary strictures because of the small sample size and the lack of better control groups in previous studies. Thus, prospective randomized studies with a large sample size are needed to establish the optimal mode of PBD and to evaluate the potential benefits of PBD in patients with both distal and proximal biliary obstructions. PMID- 26138073 TI - The Effective Application of Biased Signaling to New Drug Discovery. AB - The ability of agonists to selectively activate some but not all signaling pathways linked to pleiotropically signaling receptors has opened the possibility of obtaining molecules that emphasize beneficial signals, de-emphasize harmful signals, and concomitantly deemphasize harmful signals while blocking the harmful signals produced by endogenous agonists. The detection and quantification of biased effects is straightforward, but two important factors should be considered in the evaluation of biased effects in drug discovery. The first is that efficacy, and not bias, determines whether a given agonist signal will be observed; bias only dictates the relative concentrations at which agonist signals will appear when they do appear. Therefore, a Cartesian coordinate system plotting relative efficacy (on a scale of Log relative Intrinsic Activities) as the ordinates and Log(bias) as the abscissae is proposed as a useful tool in evaluating possible biased molecules for progression in discovery programs. Second, it should be considered that the current scales quantifying bias limit this property to the allosteric vector (ligand/receptor/coupling protein complex) and that whole-cell processing of this signal can completely change measured bias from in vitro predictions. PMID- 26138071 TI - Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease. AB - In the past decades, continuous effort has been paid to deeply understanding the pathophysiology of inflammatory bowel diseases (IBD), such as ulcerative colitis or Crohn's disease. As the disease typically arises as chronic inflammation of the gastrointestinal mucosa, research has been focused on how such an uncontrolled, deleterious immune response may arise and persist in a certain cohort of patients. Based on those immunologic analyses, the establishment of anti-TNF-alpha therapy, and the following series of biologic agents achieved great success and dramatically changed the therapeutic strategy of IBD patients. However, to guarantee long-term remission of the disease, the therapeutic standard has been raised to achieve "mucosal healing", which requires complete repair of the gastrointestinal mucosa. Recent studies have revealed the unexpected importance of epithelial cells in the pathophysiology of IBD. The general barrier function as well as the cell lineage-specific functions have been deeply attributed to the development of chronic intestinal inflammation. Also, the groundbreaking establishment of the in vitro intestinal stem cell culture system has opened up a way of developing stem cell transplantation therapy to treat otherwise refractory ulcers that may persist in IBD patients. In this review, we would like to focus on the role of epithelial cells in the pathophysiology of IBD, and also give a perspective to the upcoming development of regenerative therapies that may become one of the therapeutic choices to achieve mucosal healing in refractory patients of IBD. PMID- 26138072 TI - A Resveratrol Analogue Promotes ERKMAPK-Dependent Stat3 Serine and Tyrosine Phosphorylation Alterations and Antitumor Effects In Vitro against Human Tumor Cells. AB - (E)-4-(3,5-dimethoxystyryl)phenyl acetate (Cmpd1) is a resveratrol analog that preferentially inhibits glioma, breast, and pancreatic cancer cell growth, with IC50 values of 6-19 MUM. Notably, the human U251MG glioblastoma tumor line is the most sensitive, with an IC50 of 6.7 MUM, compared with normal fibroblasts, which have an IC50 > 20 MUM. Treatment of U251MG cells that harbor aberrantly active signal transducer and activator of transcription (Stat) 3 with Cmpd1 suppresses Stat3 tyrosine705 phosphorylation in a dose-dependent manner in parallel with the induction of pserine727 Stat3 and extracellular signal-regulated kinase/mitogen activated protein kinase 1/2 (pErk1/2(MAPK)). Inhibition of pErk1/2(MAPK) induction by the mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor PD98059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one] blocked both the pserine727 Stat3 induction and ptyrosine705 Stat3 suppression by Cmpd1, indicating dependency on the mitogen-activated protein/extracellular signal-regulated kinase kinase-Erk1/2(MAPK) pathway for Cmpd1-induced modulation of Stat3 signaling. Cmpd1 also blocked epidermal growth factor-stimulated pStat1 induction, whereas upregulating pSrc, pAkt, p-p38, pHeat shock protein 27, and pmammalian target of rapamycin levels. However, pJanus kinase 2 and pEpidermal growth factor receptor levels were not significantly altered. Treatment of U251MG cells with Cmpd1 reduced in vitro colony formation, induced cell cycle arrest in the G2/M phase and cleavage of caspases 3, 8, and 9 and poly(ADP ribose) polymerase, and suppressed survivin, myeloid cell leukemia 1, Bcl-xL, cyclin D1, and cyclin B1 expression. Taken together, these data identify a novel mechanism for the inhibition of Stat3 signaling by a resveratrol analog and suggest that the preferential growth inhibitory effects of Cmp1 occur in part by Erk1/2(MAPK) dependent modulation of constitutively active Stat3. PMID- 26138074 TI - G Protein-Coupled Receptor Multimers: A Question Still Open Despite the Use of Novel Approaches. AB - Heteromerization of G protein-coupled receptors (GPCRs) can significantly change the functional properties of involved receptors. Various biochemical and biophysical methodologies have been developed in the last two decades to identify and functionally evaluate GPCR heteromers in heterologous cells, with recent approaches focusing on GPCR complex stoichiometry and stability. Yet validation of these observations in native tissues is still lagging behind for the majority of GPCR heteromers. Remarkably, recent studies, particularly some involving advanced fluorescence microscopy techniques, are contributing to our current knowledge of aspects that were not well known until now, such as GPCR complex stoichiometry and stability. In parallel, a growing effort is being applied to move the field forward into native systems. This short review will highlight recent developments to study the stoichiometry and stability of GPCR complexes and methodologies to detect native GPCR dimers. PMID- 26138075 TI - Estimation of divergence from Hardy-Weinberg form. AB - The Hardy-Weinberg (HW) principle explains how random mating (RM) can produce and maintain a population in equilibrium, that is, with constant genotypic proportions. When proportions diverge from HW form, it is of interest to estimate the fixation index F, which reflects the degree of divergence. Starting from a sample of genotypic counts, a mixed procedure gives first the orthodox estimate of gene frequency q and then a Bayesian estimate of F, based on a credible prior distribution of F, which is described here. PMID- 26138076 TI - Paraspinal muscle denervation and balance impairment in lumbar spinal stenosis. AB - INTRODUCTION: Denervation of the paraspinal muscles may impair posture and displace the center of gravity. Therefore, we assessed balance impairment in patients with lumbar spinal stenosis (LSS) with and without paraspinal denervation. METHODS: Thirty-two women with LSS (15 symptomatic, 17 asymptomatic), aged 42-78 years, were assessed for disability, pain, and mobility, and underwent masked mini-paraspinal mapping (mPSM). Berg Balance Scale (BBS) and device-assisted balance (DAB) tests were used for balance assessment. RESULTS: The symptomatic group had worse balance and higher mPSM scores than the asymptomatic group. Among DAB tests, limit of stability (LOS) had the highest correlations with BBS and mPSM in the symptomatic group. CONCLUSIONS: Paraspinal denervation correlated highly with static and dynamic balance in symptomatic patients. We recommend paraspinal mapping, balance assessment, rehabilitation, and follow-up with the LOS test for symptomatic patients. PMID- 26138077 TI - Extraction of 3D Femur Neck Trabecular Bone Architecture from Clinical CT Images in Osteoporotic Evaluation: a Novel Framework. AB - The early detection of osteoporosis risk enhances the lifespan and quality of life of an individual. A reasonable in-vivo assessment of trabecular bone strength at the proximal femur helps to evaluate the fracture risk and henceforth, to understand the associated structural dynamics on occurrence of osteoporosis. The main aim of our study was to develop a framework to automatically determine the trabecular bone strength from clinical femur CT images and thereby to estimate its correlation with BMD. All the 50 studied south Indian female subjects aged 30 to 80 years underwent CT and DXA measurements at right femur region. Initially, the original CT slices were intensified and active contour model was utilised for the extraction of the neck region. After processing through a novel process called trabecular enrichment approach (TEA), the three dimensional (3D) trabecular features were extracted. The extracted 3D trabecular features, such as volume fraction (VF), solidity of delta points (SDP) and boundness, demonstrated a significant correlation with femoral neck bone mineral density (r = 0.551, r = 0.432, r = 0.552 respectively) at p < 0.001. The higher area under the curve values of the extracted features (VF: 85.3 %; 95CI: 68.2-100 %, SDP: 82.1 %; 95CI: 65.1-98.9 % and boundness: 90.4 %; 95CI: 78.7-100 %) were observed. The findings suggest that the proposed framework with TEA method would be useful for spotting women vulnerable to osteoporotic risk. PMID- 26138078 TI - 'Solving' nursing shortages: do we need a New Agenda? PMID- 26138079 TI - Motion-induced blindness continues outside visual awareness and without attention. AB - Visual phenomena demonstrating striking perceptual disappearances of salient stimuli have fascinated researchers because of their utility in identifying neural processes that underlie subjective visibility and invisibility. Motion induced blindness (MIB) is appealing for such purposes because it, like a class of ostensibly related paradigms such as binocular rivalry, features periods of unequivocal subjective disappearances despite constant physical stimulation. It remains unclear, however, exactly how the mechanisms that cause MIB are related to subjectively observed fluctuations in visual awareness. To address this question, we used continuous flash suppression (CFS) to present the MIB stimulus outside visual awareness. Results indicated that MIB occasionally reappeared from suppression with its salient yellow target absent. To quantify this observation, we measured reaction times (RTs) to detect the yellow dot target following visible or perceptually suppressed MIB and indeed found no difference in RTs between these conditions. We also provide evidence that MIB fluctuations can occur without attention. In sum, these experiments indicate that MIB fluctuations are effectively changes in stimulus strength, which under typical conditions result in unmistakable subjective disappearances, but are not inherently fluctuations in stimulus visibility. More broadly, these results challenge the assumed privileged link between bistable stimuli and visual awareness. PMID- 26138081 TI - Evaluation of Salt Intake, Urinary Sodium Excretion and Their Relationship to Overhydration in Chronic Kidney Disease Patients. AB - The purpose of this study was to estimate sodium intake in a group of patients with chronic kidney disease (CKD) and to correlate the results with the urinary excretion values of sodium and signs of fluid overload. We included patients with CKD in different stages. Urinary sodium was measured in 24 h urine samples. Body composition monitor (BCM) was used to estimate the hydration status. Sixty patients (38 +/- 15 ml/min of GFR) presented 4.14 +/- 1.71 g/24 h of urinary sodium excretion. Overhydration was detected in 50% of the patients by the BCM. There was a positive correlation between the measured sodium excretion values and BCM, ICW, ECW and TBW. In conclusion, markers of overhydration evaluated by BCM were positively correlated with urinary sodium excretion. PMID- 26138080 TI - Growth performance, serum biochemical profile, jejunal morphology, and the expression of nutrients transporter genes in deoxynivalenol (DON)- challenged growing pigs. AB - BACKGROUND: Fusarium infection with concurrent production of deoxynivalenol (DON) causes an increasing safety concern with feed worldwide. This study was conducted to determine the effects of varying levels of DON in diets on growth performance, serum biochemical profile, jejunal morphology, and the differential expression of nutrients transporter genes in growing pigs. RESULTS: A total of twenty-four 60 day-old healthy growing pigs (initial body weight = 16.3 +/- 1.5 kg SE) were individually housed and randomly assigned to receive one of four diets containing 0, 3, 6 or 12 mg DON/kg feed for 21 days. Differences were observed between control and the 12 mg/kg DON treatment group with regards to average daily gain (ADG), although the value for average daily feed intake (ADFI) in the 3 mg/kg DON treatment group was slightly higher than that in control (P<0.01). The relative liver weight in the 12 mg/kg DON treatment group was significantly greater than that in the control (P<0.01), but there were no significant differences in other organs. With regard to serum biochemistry, the values of blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate amino transferase (AST) in the 3 treatment groups were higher than those in the control, and the serum concentrations of L-valine, glycine, L-serine, and L glutamine were significantly reduced in the 3 treatment groups, especially in the 12 mg/kg DON group (P<0.01). Serum total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) were markedly decreased after exposure to DON contaminated feeds (P<0.01). The villi height was markedly decreased and the lymphocyte cell numbers markedly increased in the 3 DON contaminated feeds (P<0.01). The mRNA expression levels of excitatory amino acid transporter-3 (EAAC 3), sodium-glucose transporter-1 (SGLT-1), dipeptide transporter-1 (PepT-1), cationic amino acid transporter-1 (CAT-1) and y(+)L-type amino acid transporter-1 (LAT-1) in control were slightly or markedly higher than those in the 3 DON treatment groups. CONCLUSIONS: These results showed that feeds containing DON cause a wide range of effects in a dose-dependent manner. Such effects includes weight loss, live injury and oxidation stress, and malabsorption of nutrients as a result of selective regulation of nutrient transporter genes such as EAAC-3, SGLT-1, PepT-1, CAT-1 and LAT-1. PMID- 26138082 TI - Reply to The long and winding road in cancer survivorship care. PMID- 26138083 TI - Assessing the predictive power of newly added biomarkers. AB - As medical research and technology advance, there are always new biomarkers found and predictive models proposed for improving the diagnostic performance of diseases. Therefore, in addition to the existing biomarkers and predictive models, how to assess new biomarkers becomes an important research problem. Many classification performance measures, which are usually based on the performance on the whole cut-off values, were applied directly to this type of problems. However, in a medical diagnosis, some cut-off points are more important, such as those points within the range of high specificity. Thus, as the partial area under the ROC curve to the area under ROC curve, we study the partial integrated discriminant improvement (pIDI) for evaluating the predictive ability of a newly added marker at a prespecified range of cut-offs. Theoretical property of estimate of the proposed measure is reported. The performance of this new measure is then compared with that of the partial area under an ROC curve. The numerical results use synthesized are presented, and a liver cancer dataset is used for demonstration purposes. PMID- 26138084 TI - Modulation of surface plasmon coupled emission (SPCE) by a pulsed magnetic field. AB - The unique modulation of surface plasmon coupled emission (SPCE) on a Au/Cr/Co/Cr/glass substrate by an external magnetic field has been observed. The most positive regulation was triggered by employing the multilayered substrate with a 7.5 nm-thick Co layer. The new magnetoplasmonic strategy provides a simple way to modulate the SPCE signal. PMID- 26138085 TI - Current Status of Left Ventricular Assist Devices and Cell Sheet Engineering for Treatment of Severe Heart Disease in Japan. PMID- 26138087 TI - Discrimination of the prochiral hydrogens at the C-2 position of n-alkanes by the methane/ammonia monooxygenase family proteins. AB - The selectivity of ammonia monooxygenase from Nitrosomonas europaea (AMO-Ne) for the oxidation of C4-C8n-alkanes to the corresponding alcohol isomers was examined to show the ability of AMO-Ne to recognize the n-alkane orientation within the catalytic site. AMO-Ne in whole cells produces 1- and 2-alcohols from C4-C8n alkanes, and the regioselectivity is dependent on the length of the carbon chain. 2-Alcohols produced from C4-C7n-alkanes were predominantly either the R- or S enantiomers, while 2-octanol produced from n-octane was racemic. These results indicate that AMO-Ne can discriminate between the prochiral hydrogens at the C-2 position, with the degree of discrimination varying according to the n-alkane. Compared to the particulate methane monooxygenase (pMMO) of Methylococcus capsulatus (Bath) and that of Methylosinus trichosporium OB3b, AMO-Ne showed a distinct ability to discriminate between the orientation of n-butane and n pentane in the catalytic site. PMID- 26138088 TI - The Lee Silverman Voice Treatment (LSVT(r)) speech therapy in progressive supranuclear palsy. AB - BACKGROUND: The Lee Silverman Voice Treatment (LSVT(r)) was specifically created and tested to comply with the needs of individuals with Parkinson's disease (PD) and other neurological problems. This is a high effort intensive treatment that aims at increasing vocal intensity through the increase of subglottal air pressure, i.e. respiratory effort, for a better cordal adduction and vibration, following the motto "think loud". AIM: The main goal of this study is to inspect the efficacy of LSVT(r) treatment in progressive supranuclear palsy (PSP) patients. DESIGN: Longitudinal study. SETTING: Rehabilitative inpatient unit. POPULATION: Sixteen patients with PSP and 23 patients with idiopathic PD as control were enrolled in the study. METHODS: All patients underwent a training consisting in16 sessions of speech therapy following the LSVT(r) protocol. Initially the two groups of patients had similar voice problems, i.e. low volume and bad articulation of speech. RESULTS: A statistically significant improvement was found among the data collected before and after treatment in the PSP and Parkinson groups. Increase in maximum phonation duration and volume of voice in reading were similar in the two groups. Improvement in quality of voice and articulation were more significant in the PD group as compared to the PSP group. CONCLUSION: These results, along with previous findings, add further support to the generalized therapeutic impact of intensive voice treatment on respiratory and laryngeal functions in individuals with PSP. CLINICAL REHABILITATION IMPACT: The positive results, the absence of dropout and collateral effect following this clinical treatments with LSVT technique encouraged to use this technique in PSP patients. PMID- 26138089 TI - A proposal for an Italian minimum data set assessment protocol for robot-assisted rehabilitation: a Delphi study. AB - BACKGROUND: At present there is no agreement on a common evaluation protocol to assess improvement in stroke patients after robotic therapy. AIM: The aim of this study was to identify a Minimum Data Set Assessment Protocol, using an agreement based survey. DESIGN: A Delphi survey. SETTING: This study was conceived by the Italian Robotic Neurorehabilitation Research Group (IRNRG), an Italian group involved in the clinical application of robot-assisted rehabilitation devices POPULATION: Stroke subjects. METHODS: A 3-round Delphi survey was carried out through the electronic submission of questionnaires to a panel of experts identified in fourteen rehabilitation centers. For each generated item, experts were asked to rate questions on a 5 point Likert Scale. RESULTS: After the 1st round the questionnaire was filled out by 43 (84.3%) out of 51 experts invited to participate in the study. In the 2nd and 3rd rounds we explored the specific evaluation tools for each of the ICF domains identified in the 1st round. The experts identified the following assessment tools for the upper limb: the Ashworth Scale, the Fugl-Meyer assessment scale, the Frenchay Arm Test, the Medical Research Council scale, the Motricity Index, Frenchay Activities Index and Modified Barthel Index; and for the lower limb: the Ashworth Scale, the Motricity Index, the 10 meter walking Test, the 6 minutes walking Test, the Functional Ambulatory Classification, the Timed Up and Go Test, the Walking Handicap Scale, the Borg Rating of Perceived Exertion, the Heart Rate, the Medical Research Council Scale, the Tinetti Balance Scale and the Modified Barthel Index. CONCLUSION: The Delphi survey presented in this study allows the identification of a shared assessment protocol to be applied in clinical practice and research for the evaluation of the real improvement related to robot-assisted rehabilitation of the upper and lower limb in patients after stroke. CLINICAL REHABILITATION IMPACT: Clinicians and researchers could use the results of this study to obtain a common language in robotic rehabilitation assessments. PMID- 26138090 TI - Complementary physical therapies for movement disorders in Parkinson's disease: a systematic review. AB - BACKGROUND: The growth and popularity of complementary physical therapies for Parkinson's disease (PD) attempt to fill the gap left by conventional exercises, which does not always directly target wellbeing, enjoyment and social participation. AIM: To evaluate the effects of complementary physical therapies on motor performance, quality of life and falls in people living with PD. DESIGN: Systematic review with meta-analysis. POPULATION: Outpatients--adults diagnosed with idiopathic PD, male or female, modified Hoehn and Yahr scale I-IV, any duration of PD, any duration of physical treatment or exercise. METHODS: Randomized controlled trials, non-randomized controlled trials and case series studies were identified by systematic searching of health and rehabilitation electronic databases. A standardized form was used to extract key data from studies by two independent researchers. RESULTS: 1210 participants from 20 randomized controlled trials, two non-randomized controlled trials and 13 case series studies were included. Most studies had moderately strong methodological quality. Dancing, water exercises and robotic gait training were an effective adjunct to medical management for some people living with PD. Virtual reality training, mental practice, aerobic training, boxing and Nordic walking training had a small amount of evidence supporting their use in PD. CONCLUSION: On balance, alternative physical therapies are worthy of consideration when selecting treatment options for people with this common chronic disease. CLINICAL REHABILITATION IMPACT: Complementary physical therapies such as dancing, hydrotherapy and robotic gait training appear to afford therapeutic benefits, increasing mobility and quality of life, in some people living with PD. PMID- 26138092 TI - Why clinicians still use community treatment orders. PMID- 26138091 TI - Parathyroid Hormone Levels in Healthy Children and Adolescents. AB - BACKGROUND: Parathyroid hormone (PTH) is important in the assessment of calcium metabolism disorders. However, there are few data regarding PTH levels in childhood and adolescence. AIM: The aim of this study was to determine PTH levels in a large group of healthy children and adolescents. PATIENTS AND METHODS: We retrospectively evaluated PTH levels in 1,580 healthy Caucasian children and adolescents (849 females, 731 males, aged 2.0-17.2 years) with 25-hydroxyvitamin D [25(OH)D] levels >= 30 ng/ml. All subjects with genetic, endocrine, hepatic, renal, or other known diseases were excluded. RESULTS: The serum intact PTH concentration (median and inter-quartile range) was 23.00 (15.00-31.60) pg/ml. In our population, the mean 25(OH)D value was 34.27 +/- 4.12 ng/ml. The median PTH concentration in boys was 23.00 (15.00-32.00) pg/ml, whereas in girls it was 23.10 (15.00-31.10) pg/ml. However, in girls, PTH levels significantly increased in the age group of 8.1-10.0 years compared to the age group of 2.1-4.0 years (p < 0.0001), whereas in boys it significantly increased in the age groups of 10.1 12.0 years (p < 0.0001) and 12.1-14.0 years (p < 0.0001), leading to the hypothesis of a relationship between PTH level and pubertal and bone growth spurts. CONCLUSIONS: PTH levels in healthy children and adolescents covered a narrower range than the adult values. Obtaining reference values of PTH in childhood and adolescence could aid in the estimation of appropriate values of bone metabolites. PMID- 26138093 TI - Spatiotemporal variation and social determinants of suicide in China, 2006-2012: findings from a nationally representative mortality surveillance system. AB - BACKGROUND: Suicide in China has declined since the 1990s. However, there has been limited investigation of the potential spatiotemporal variation and social determinants of suicide during subsequent periods. METHOD: Annual suicide counts from 2006 to 2012 stratified by county, 5-year age group (?15 years) and gender were obtained from the Chinese Disease Surveillance Points system. Trends and geographic differentials were examined using multilevel negative binomial regression models to explore spatiotemporal variation in suicide, and the role of key sociodemographic factors associated with suicide. RESULTS: The suicide rate (per 100 000) in China decreased from 14.7 to 9.1, 2006-2012. Rates of suicide were higher in males than females and increased substantially with age. Suicide rates were higher in rural areas compared with urban areas; however, urban-rural disparities reduced over time with a faster decline for rural areas. Within both urban and rural areas, higher rates of suicide were evident in areas with lower socio-economic circumstances (SEC) [rate ratio (RR) 1.85, 95% confidence interval (CI) 1.31-2.62]. Suicide rates varied more than twofold (median RR 2.06) across counties, and were highest in central and southwest regions of China. A high proportion of the divorced population, especially for younger females, was associated with lower suicide rates (RR 0.60, 95% CI 0.46-0.79). CONCLUSIONS: Geographic variations for suicide should be taken into account in policy making, particularly for older males living in rural areas and urban areas with low SEC. Measures to reduce disparities in socio-economic level and alleviate family relation stress are current priorities. PMID- 26138094 TI - Nickel hexacyanoferrate as suitable alternative to Ag for electrochemical lithium recovery. AB - Currently, Li is mainly produced through evaporation of Li-rich brines obtained from South American countries such as Bolivia, Chile, and Argentina. The most commonly used process, the lime-soda evaporation, requires a long time and several purification steps, which produces a considerable amount of chemical waste. Various electrochemical methods have been proposed as alternatives, but they use expensive metals such as Ag or Pt, thus rendering these methods economically unacceptable. In this work, we present KNiFe(CN)6 , an abundant and environmentally friendly material, as alternative to these expensive components. The Prussian blue derivate has a higher affinity toward cations (Na(+) or K(+) ) than for Li(+) . Additionally, the use of KNiFe(CN)6 permits the utilization of seawater or brine water as recovery solution, thus reducing the consumption of fresh water, which is typically a scarce element in Li production sites. PMID- 26138095 TI - The role of p19 and p21 H-Ras proteins and mutants in miRNA expression in cancer and a Costello syndrome cell model. AB - BACKGROUND: P19 H-Ras, a second product derived from the H-Ras gene by alternative splicing, induces a G1/S phase delay, thereby maintaining cells in a reversible quiescence state. When P21 H-Ras is mutated in tumour cells, the alternative protein P19 H-Ras is also mutated. The H-Ras mutation Q61L is frequently detected in different tumours, which acts as constitutive activator of Ras functions and is considered to be a strong activating mutant. Additionally, a rare congenital disorder named Costello Syndrome, is described as a H-Ras disorder in children, mainly due to mutation G12S in p19 and p21 H-Ras proteins, which is present in 90 % of the Costello Syndrome patients. Our aim is to better understand the role of p19 and p21 H-Ras proteins in the cancer and Costello Syndrome development, concerning the miRNAs expression. METHODS: Total miRNAs expression regulated by H-Ras proteins were first analyzed in human miRNA microarrays assays. Previously selected miRNAs, were further analyzed in developed cell lines containing H-Ras protein mutants, that included the G12S Costello Syndrome mutant, with PCR Real-Time Taq Man miRNA Assays primers. RESULTS: This study describes how p19 affects the RNA world and shows that: i) miR-342, miR-206, miR-330, miR-138 and miR-99b are upregulated by p19 but not by p19W164A mutant; ii) anti-miR-206 can restore the G2 phase in the presence of p19; iii) p19 and p21Q61L regulate their own alternative splicing; iv) miR-206 and miR-138 are differentially regulated by p19 and p21 H-Ras and v) P19G12S Costello mutants show a clear upregulation of miR-374, miR-126, miR-342, miR-330, miR-335 and let-7. CONCLUSIONS: These results allow us to conclude that the H-Ras G12S mutation plays an important role in miRNA expression and open up a new line of study to understand the consequences of this mutation on Costello syndrome. Furthermore, they suggest that oncogenes may have a sufficiently important impact on miRNA expression to promote the development of numerous cancers. PMID- 26138096 TI - Cyanidin-3-O-glucoside Induces Apoptosis and Inhibits Migration of Tumor Necrosis Factor-alpha-Treated Rat Aortic Smooth Muscle Cells. AB - Blueberries are rich in anthocyanins (ACNs), which have recently been noted to protect against atherosclerosis development in mice. Cyanidin-3-O-glucoside (C3G), a member of blueberry ACN family, can inhibit the tumor necrosis factor alpha (TNF-alpha)-induced proliferation of vascular smooth muscle cells (VSMCs). However, the effects of C3G on VSMC apoptosis and migration remain unclear. This study was thus conducted to examine whether and how C3G affected the apoptosis and migration of rat aortic smooth muscle cells (RASMCs) challenged by TNF-alpha. Primary cultured RASMCs were pretreated with C3G (25, 50 or 100 MUM) for 2 h and then stimulated with TNF-alpha (10 ng/ml) for additional 24 h. Our results illustrated that C3G pretreatment induced significant apoptosis in TNF-alpha stimulated RASMCs in a dose-dependent way, which was accompanied with increased cleaved caspase-3, caspase-9 and Bax and decreased Bcl-2. Moreover, RASMC migration was enhanced by TNF-alpha, but markedly suppressed by C3G pretreatment. The expressions and activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 were inhibited by C3G. In addition, TNF-alpha-enhanced nuclear translocation of nuclear factor kappa B (NF-kappaB) subunit p65 and phosphorylation of NF-kappaB inhibitor alpha (IkappaBalpha) in RASMCs were attenuated by C3G. In summary, our study reveals that C3G can induce significant apoptosis in TNF-alpha-treated RASMCs and markedly inhibit their migration. PMID- 26138097 TI - We can eliminate maternal deaths in resource-poor countries. PMID- 26138098 TI - [Recurrent swelling of parotid gland in children]. PMID- 26138099 TI - [Injectable filling materials]. PMID- 26138100 TI - Effects of birth-rearing type on weaning weights in meat sheep are systematically associated with differences in mean performance among flocks. AB - BACKGROUND: Adjustment of body weights for systematic environmental effects such as dam age and litter size is essential for accurate prediction of breeding values in meat sheep and often accomplished by pre-adjusting records using simple multiplicative adjustment factors, which are derived as ratios of least-squares means of weights of lambs in target and reference classes. However, increasing use of multibreed genetic evaluations that incorporate data from both purebred and commercial flocks has generated concerns regarding the ability of simple additive or multiplicative adjustment factors to properly correct for environmental effects in flocks that differ widely in mean performance. Thus, consistency of adjustment factors across flocks and systematic effects of the level of flock performance on these factors were evaluated using data from the US National Sheep Improvement Program. METHODS: We used birth and weaning weights of lambs from 29 flocks that had at least 500 records per flock and represented several terminal-sire sheep breeds. Effects of lamb sex, dam age class and litter size on birth weights, and of dam age class and combined effects of type of birth and rearing on weaning weights were evaluated. Interactions between these effects and flock were assessed. Bias associated with different adjustment protocols was evaluated for high- and low-performance flocks. RESULTS: Effects of litter size and differences between yearling and adult dams varied (P < 0.001) among flocks. For weaning weights, additive adjustment factors were not associated with the level of flock performance, but multiplicative adjustment factors were strongly and inversely related to flock means for weaning weights (W). Flock-specific adjustment factors (F = alphaW(beta)) reduced bias in adjusted weaning weights associated with differences in flock performance. By contrast, simple multiplicative adjustment factors were appropriate to adjust birth weights. CONCLUSIONS: Differences in weaning weights among single, twin, and triplet lambs were inversely related to the level of flock performance. Use of simple multiplicative adjustment factors led to adjustment bias when applied across flocks with large differences in mean performance. This bias was reduced by using additive adjustment factors or multiplicative factors that were derived as simple exponential functions of flock means for weaning weight. PMID- 26138101 TI - Host ER stress during malaria parasite infection. PMID- 26138102 TI - Ethics and germline gene editing. PMID- 26138103 TI - Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness. AB - The global spread of dengue virus (DENV) infections has increased viral genetic diversity, some of which appears associated with greater epidemic potential. The mechanisms governing viral fitness in epidemiological settings, however, remain poorly defined. We identified a determinant of fitness in a foreign dominant (PR 2B) DENV serotype 2 (DENV-2) clade, which emerged during the 1994 epidemic in Puerto Rico and replaced an endemic (PR-1) DENV-2 clade. The PR-2B DENV-2 produced increased levels of subgenomic flavivirus RNA (sfRNA) relative to genomic RNA during replication. PR-2B sfRNA showed sequence-dependent binding to and prevention of tripartite motif 25 (TRIM25) deubiquitylation, which is critical for sustained and amplified retinoic acid-inducible gene 1 (RIG-I) induced type I interferon expression. Our findings demonstrate a distinctive viral RNA-host protein interaction to evade the innate immune response for increased epidemiological fitness. PMID- 26138105 TI - Heavy fermions. Unconventional Fermi surface in an insulating state. AB - Insulators occur in more than one guise; a recent finding was a class of topological insulators, which host a conducting surface juxtaposed with an insulating bulk. Here, we report the observation of an unusual insulating state with an electrically insulating bulk that simultaneously yields bulk quantum oscillations with characteristics of an unconventional Fermi liquid. We present quantum oscillation measurements of magnetic torque in high-purity single crystals of the Kondo insulator SmB6, which reveal quantum oscillation frequencies characteristic of a large three-dimensional conduction electron Fermi surface similar to the metallic rare earth hexaborides such as PrB6 and LaB6. The quantum oscillation amplitude strongly increases at low temperatures, appearing strikingly at variance with conventional metallic behavior. PMID- 26138104 TI - Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys. AB - Preclinical studies of viral vector-based HIV-1 vaccine candidates have previously shown partial protection against neutralization-resistant virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy of adenovirus serotype 26 (Ad26) vector priming followed by purified envelope (Env) glycoprotein boosting. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env, Gag, and Pol and boosted with AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete protection in 50% of vaccinated animals against a series of repeated, heterologous, intrarectal SIVmac251 challenges that infected all controls. Protective efficacy correlated with the functionality of Env-specific antibody responses. Comparable protection was also observed with a similar Ad/Env vaccine against repeated, heterologous, intrarectal SHIV-SF162P3 challenges. These data demonstrate robust protection by Ad/Env vaccines against acquisition of neutralization-resistant virus challenges in rhesus monkeys. PMID- 26138107 TI - Erratum to: New C2 synchondrosal fracture classification system. PMID- 26138108 TI - Biofabricated nanoparticle coating for liver-cell targeting. AB - Biology routinely uses noncovalent interactions to perform complex functions that range from the molecular recognition of ligand-receptor binding to the reversible self-assembly/disassembly of hierarchical nanostructures (e.g., virus particles). Potentially, biological materials that offer such recognition and reversible self assembly functionality can be applied to nanomedicine. Here, polysaccharides with the multifunctional polysaccharide-binding protein Concanavalin A (Con A) are coupled to create a functional nanoparticle coating. This coating is self assembled in a layer-by-layer format by sequentially contacting a nanoparticle with Con A and the polysaccharide glycogen. In the final assembly step, a galactomannan targeting ligand is self-assembled into the coating. Evidence indicates that the mannose residues of the galactomannan backbone are responsible for assembly into the coating by Con A binding, while the galactose side chain residues are responsible for targeting to the liver-specific asialoglycoprotein receptor (ASGP-R). Binding to ASGP-R induces endocytic uptake, while the low endosomal pH triggers disassembly of the coating and release of the nanoparticle entrapped drug. In vitro cell studies indicate that the coating confers liver cell-specific function for both nanoparticle uptake and drug delivery. These studies extend the use of Con A to sugar-mediated and organ-specific targeting, and further illustrate the potential of biologically based fabrication for generating functional materials. PMID- 26138109 TI - Dorsal versus ventral onlay buccal mucosal graft urethroplasty for long-segment bulbar urethral stricture: A prospective randomized study. AB - OBJECTIVES: To compare safety and efficacy of ventral versus dorsal onlay buccal mucosal graft urethroplasty in patients with long-segment incomplete bulbar urethral stricture. METHODS: This was a single center, prospective, randomized trial. Patients with long-segment (>2 cm) incomplete bulbar urethral stricture and meeting eligibility criteria were enrolled in the study. They were randomized into two study groups: group A undergoing dorsal onlay buccal mucosal graft urethroplasty and group B undergoing ventral onlay buccal mucosal graft urethroplasty. The two groups were compared statistically with regard to International Prostate Symptom Score, maximum flow rate, intraoperative parameters and complications. RESULTS: A total of 80 eligible patients were randomized into two equal groups of 40 patients each. The preoperative International Prostate Symptom Score, maximum flow rate and intraoperative parameters were not significantly different between the two groups. At 12-month follow up, the mean International Prostate Symptom Score showed 324.95% and 353.59% improvement, whereas the mean maximum flow rate showed 208.43% and 201.93% improvement in group A and B, respectively. There was no significant difference between International Prostate Symptom Score and maximum flow rate data between the two groups at 3- and 12-month follow up. The success rate of surgery was similar between group A and B (92.5% vs 90%) with no significant difference noted between them. CONCLUSION: Dorsal and ventral onlay buccal mucosal graft urethroplasty have comparable efficacy and complication rates for treatment of long-segment incomplete bulbar urethral strictures. PMID- 26138106 TI - Pheochromocytoma: Gasping for Air. AB - There has been increasing evidence that pseudohypoxia--a phenomenon that we refer to as "gasping for air"--along with mitochondrial enzyme dysregulation play a crucial role in tumorigenesis, particularly in several hereditary pheochromocytomas (PHEOs) and paragangliomas (PGLs). Alterations in key tricarboxylic acids (TCA) cycle enzymes (SDH, FH, MDH2) have been shown to induce pseudohypoxia via activation of the hypoxia-inducible transcription factor (HIF) signaling pathway that is involved in tumorigenesis, invasiveness, and metastatic spread, including an association with resistance to various cancer therapies and worse prognosis. This review outlines the ongoing story of the pathogenesis of hereditary PHEOs/PGLs, showing the unique and most updated evidence of TCA cycle dysregulation that is tightly linked to hypoxia signaling. PMID- 26138110 TI - CT-guided permanent 125I seed interstitial brachytherapy for recurrent retroperitoneal lymph node metastases after external beam radiotherapy. AB - PURPOSE: To evaluate the feasibility, efficacy, and safety of permanent (125)I seed interstitial brachytherapy reirradiation in patients with retroperitoneal lymph node recurrence under CT guidance. METHODS AND MATERIALS: Seventeen patients with 19 retroperitoneal lymph node recurrence after external beam radiotherapy underwent CT-guided (125)I seed implant brachytherapy from October 2007 to August 2014. Treatment for all patients was preplanned using a three dimensional radiation therapy planning system 3-5 days before brachytherapy; dosimetry verification was performed immediately after brachytherapy. RESULTS: The actuarial D90 (dose delivered to 90% of the target volume) was 100-198 Gy (median, 126.5 Gy). In 9 patients, pain intensity decreased to mild pain 1-3 weeks after brachytherapy. Pain-free survival ranged 2-15 months (median, 5 months; 95% confidence interval [CI]: 0.1, 9.9). The overall response rate was 19 of 19 (100%). The median local control time was 15 months (95% CI: 2.3, 27.7). The 6-, 12-, and 24-month local control rate was 88.0%, 63.2%, and 42.1%, respectively. Twelve patients (70.6%) developed distant metastases and died. Two patients (11.8%) are alive with distant metastases but no evidence of local recurrence. Three patients (17.6%) are alive with no evidence of local recurrence. Median overall survival was 10 months (95% CI: 5.7, 14.3); the 1- and 2-year survival rates were 38.1% and 15.3%, respectively. No major complications related to the procedure occurred during or after brachytherapy. CONCLUSIONS: Reirradiation with CT-guided permanent (125)I seed interstitial brachytherapy is feasible, safe, and effective as pain relief or salvage treatment for patients with recurrent retroperitoneal lymph nodes. PMID- 26138111 TI - Safety of vedolizumab in the treatment of Crohn's disease and ulcerative colitis. AB - INTRODUCTION: Vedolizumab is the latest FDA-approved anti-integrin therapy for treatment of moderate-to-severe inflammatory bowel disease (IBD). The safety and efficacy of vedolizumab have been studied in short-term clinical trials. AREAS COVERED: This paper reviews the safety profile of vedolizumab compared with other biologics. It also highlights the mechanism of action of the medication. We discuss the current position of vedolizumab in our current algorithm for IBD management and comment on future prospects of the drug. EXPERT OPINION: Vedolizumab appears to be a safe and effective option in the treatment of moderate-to-severe IBD in the short term. Long-term observational studies and post-marketing safety data are needed to ascertain the long-term efficacy and side effect profile. PMID- 26138112 TI - [Comment on article "Anesthesiology treatment of an "open book" pelvic fracture due to an explosion"]. PMID- 26138113 TI - Photoselective Vaporization of the Prostate and Simultaneous Suprapubic Cystostomy for the Treatment of Benign Prostatic Hyperplasia in Patients with Mild to Severe Detrusor Underactivity. AB - INTRODUCTION: This study investigated the clinical efficacy and safety of photoselective vaporization of the prostate (PVP) and simultaneous suprapubic cystostomy for benign prostatic hyperplasia (BPH) in patients with mild to severe detrusor underactivity (DU). SUBJECTS AND METHODS: Seventy-eight patients with BPH were divided into 3 groups according to the severity of DU: mild DU group, moderate DU group and severe DU group. The preoperative and postoperative data, including the detrusor pressure at maximum flow (Pdetmax), bladder compliance, maximum urinary flow (Qmax), postvoid residual urine (PVR) values, International Prostate Symptom Score (IPSS) and quality of life (QoL) were evaluated. RESULTS: The therapeutic effectiveness including cure and improvement in mild and moderate DU group was significantly higher than that of the severe group. Compared to the preoperative values, Pdetmax, bladder compliance, Qmax, PVR, IPSS and QoL scores at 12 months postoperatively had significantly improved. In addition, the above parameters at 12 months postoperatively in the mild or moderate DU group had significant difference compared to the severe DU group. CONCLUSION: PVP and simultaneous suprapubic cystostomy seem to be an appropriate treatment modality in BPH patients with mild and/or moderate DU as well as in patients with severe DU and slightly reduced bladder compliance. PMID- 26138114 TI - Registry analysis supports different mechanisms for gastroschisis and omphalocele within shared developmental fields. AB - Nine thousand two hundred eighty abnormalities associated with 2,943 abdominal wall defects (AWD) encoded from 1999 to 2008 by the Texas Birth Defects Registry (TBDR) were classified and analyzed for mechanism, beginning with 1,831 gastroschisis cases, 774 (41%) with 2,368 associated anomalies (AA) and 814 of omphalocele, 727 (89%) with 4,092 AA. Typical AA profiles for Trisomy 18 (23% of omphalocele cases) and Beckwith-Wiedemann syndrome (15%) validated registry AA descriptors, chromosome disorders surprisingly accounting for 24% of known conditions with gastroschisis followed by expected amniotic band (ADAM) complex (23%) and amyoplasia/arthrogryposis (16%). Separation of known diagnoses, fetal stillbirth cases, and transitional or secondary AA left 330 cases of gastroschisis with 594 AA (452 major, 142 minor) and 295 cases of omphalocele with 956 AA (683 major, 273 minor). Anomalies suggestive of vascular origin (intestinal atresias, amyoplasia, bands) were more frequent with gastroschisis and those of defective lateral folding (exstrophies, limb-body wall defects) with omphalocele. Most AA favoring omphalocele had parallel frequencies with gastroschisis, whether by system/region-for example, cardiac AA (10% of cases), contractures (4.7%), limb (3.7%), CNS (3.2%) for gastroschisis versus cardiac (35%), contractures (14%), digestive-excretory-trunk-axial (all ~11%), CNS (9.9%) for omphalocele-or for particular minor/major AA-for example, micrognathia (0.72% versus 3.3%), spina bifida (0.59% versus 3.9%), anal atresia (0.73% versus 6.4%), two-vessel cord (0.22% versus 5.6%). Similar frequencies of many AA reflective of early patterning support common AWD origin within early developmental fields and reinforce the use of large birth defect numbers from suitably qualified registries to define anomaly mechanism as well as prevalence. PMID- 26138115 TI - Morphological features of maxillary anterior teeth in a sample of Chinese population. AB - The purpose of this study is to investigate the morphological features of maxillary anterior teeth in the Chinese population. The width-to-height ratios of these teeth and the width proportions of the central incisor and canine to the lateral incisor were calculated on the casts of 101 Chinese individuals with normal occlusion. The mean width in the sample was taken as the given lateral incisor width. The given central incisor width and canine width were decided according to the width proportion relationship. The maxillary anterior teeth with the given width were placed in the dentitions with three different types of arch forms, and the esthetic effect from the front view was analyzed. The results showed that the width-to-height ratios for the central incisor, lateral incisor, and canine were 87.75% (SD=8.31%), 84.02% (SD=7.74%), and 86.99% (SD=7.80%), respectively. The width-to-width proportions of the central incisor to lateral incisor and canine to lateral incisor were 1.19% (SD=0.09) and 1.13% (SD=0.09%), respectively. With the given maxillary anterior tooth width, the golden ratio or other recurring proportion between the teeth is not obtained in any arch form from the front view. These results lead to the conclusion that Chinese maxillary anterior teeth display a square-like form with rather high width-to-height ratios. There is the possibility that there is no golden ratio or other recurring proportion in the width relationship between the maxillary anterior teeth of Chinese individuals. PMID- 26138116 TI - Optimization of Culture Medium for Maximal Production of Spinosad Using an Artificial Neural Network - Genetic Algorithm Modeling. AB - BACKGROUND: Spinosyns, products of secondary metabolic pathway of Saccharopolyspora spinosa, show high insecticidal activity, but difficulty in enhancing the spinosad yield affects wide application. The fermentation process is a key factor in this case. METHODS: The response surface methodology (RMS) and artificial neural network (ANN) modeling were applied to optimize medium components for spinosad production using S. spinosa strain CGMCC4.1365. Experiments were performed using a rotatable central composite design, and the data obtained were used to construct an ANN model and an RSM model. Using a genetic algorithm (GA), the input space of the ANN model was optimized to obtain optimal values of medium component concentrations. RESULTS: The regression coefficients (R(2)) for the ANN and RSM models were 0.9866 and 0.9458, respectively, indicating that the fitness of the ANN model was higher. The maximal spinosad yield (401.26 mg/l) was obtained using ANN/GA-optimized concentrations. CONCLUSION: The hybrid ANN/GA approach provides a viable alternative to the conventional RSM approach for the modeling and optimization of fermentation processes. PMID- 26138117 TI - Biallelic HERC1 mutations in a syndromic form of overgrowth and intellectual disability. AB - We report two Colombian siblings affected by overgrowth, intellectual disability and facial dysmorphism. Exome (via NGS) and Sanger sequencing revealed that biallelic sequence variants in a novel gene (HERC1) might be related to the disease pathogenesis. These results provide useful data for future genotype phenotype correlations and for a molecular diagnosis of overgrowth. PMID- 26138118 TI - Poststroke Epilepsy Is Associated With a High Mortality After a Stroke at Young Age: Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation Study. AB - BACKGROUND AND PURPOSE: Poststroke epilepsy is a common complication after a young stroke. We investigated the association between poststroke epilepsy and mortality. METHODS: We performed a prospective cohort study among 631 patients with a first-ever transient ischemic attack or ischemic stroke, aged 18 to 50 years. Survival analysis and Cox proportional hazard analysis were used to estimate cumulative mortality and hazard ratios for patients with and without epilepsy. RESULTS: After mean follow-up of 12.5 years (SD 8.6), 76 (12.0%) developed poststroke epilepsy. Case fatality was 27.4% for patients with poststroke epilepsy and 2.1% for those without. Poststroke epilepsy was associated with 30-day mortality (hazard ratio, 4.8; 95% confidence interval, 1.7 14.0) and long-term mortality (hazard ratio, 1.8; 95% confidence interval, 1.2 2.9). CONCLUSIONS: Epilepsy is a common problem after a young stroke and is associated with an increased short-term and long-term mortality. PMID- 26138119 TI - Pediatric Acute Stroke Protocol Activation in a Children's Hospital Emergency Department. AB - BACKGROUND AND PURPOSE: Pediatric acute stroke teams are a new phenomenon. We sought to characterize the final diagnoses of children with brain attacks in the emergency department where the pediatric acute stroke protocol was activated and to describe the time to neurological evaluation and neuroimaging. METHODS: Clinical and demographic information was obtained from a quality improvement database and medical records for consecutive patients (age, <=20 years) presenting to a single institution's pediatric emergency department where the acute stroke protocol was activated between April 2011 and October 2014. Stroke protocol activation means that a neurology resident evaluates the child within 15 minutes, and urgent magnetic resonance imaging is available. RESULTS: There were 124 stroke alerts (age, 11.2+/-5.2 years; 63 boys/61 girls); 30 were confirmed strokes and 2 children had a transient ischemic attack. Forty-six of 124 (37%) cases were healthy children without any significant medical history. Nonstroke neurological emergencies were found in 17 children (14%); the majority were meningitis/encephalitis (n=5) or intracranial neoplasm (n=4). Other common final diagnoses were complex migraine (17%) and seizure (15%). All children except 1 had urgent neuroimaging. Magnetic resonance imaging was the first study in 76%. The median time from emergency department arrival to magnetic resonance imaging was 94 minutes (interquartile range, 49-151 minutes); the median time to computed tomography was 59 minutes (interquartile range, 40-112 minutes). CONCLUSIONS: Of pediatric brain attacks, 24% were stroke, 2% were transient ischemic attack, and 14% were other neurological emergencies. Together, 40% had a stroke or other neurological emergency, underscoring the need for prompt evaluation and management of children with brain attacks. PMID- 26138120 TI - Letter by Sanna Regarding Article, "Prognostications of Fibrillations". PMID- 26138121 TI - Therapeutically Targeting Tumor Necrosis Factor-alpha/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage. AB - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a complex stroke subtype characterized by an initial brain injury, followed by delayed cerebrovascular constriction and ischemia. Current therapeutic strategies nonselectively curtail exacerbated cerebrovascular constriction, which necessarily disrupts the essential and protective process of cerebral blood flow autoregulation. This study identifies a smooth muscle cell autocrine/paracrine signaling network that augments myogenic tone in a murine model of experimental SAH: it links tumor necrosis factor-alpha (TNFalpha), the cystic fibrosis transmembrane conductance regulator, and sphingosine-1-phosphate signaling. METHODS: Mouse olfactory cerebral resistance arteries were isolated, cannulated, and pressurized for in vitro vascular reactivity assessments. Cerebral blood flow was measured by speckle flowmetry and magnetic resonance imaging. Standard Western blot, immunohistochemical techniques, and neurobehavioral assessments were also used. RESULTS: We demonstrate that targeting TNFalpha and sphingosine-1-phosphate signaling in vivo has potential therapeutic application in SAH. Both interventions (1) eliminate the SAH-induced myogenic tone enhancement, but otherwise leave vascular reactivity intact; (2) ameliorate SAH-induced neuronal degeneration and apoptosis; and (3) improve neurobehavioral performance in mice with SAH. Furthermore, TNFalpha sequestration with etanercept normalizes cerebral perfusion in SAH. CONCLUSIONS: Vascular smooth muscle cell TNFalpha and sphingosine-1-phosphate signaling significantly enhance cerebral artery tone in SAH; anti-TNFalpha and anti-sphingosine-1-phosphate treatment may significantly improve clinical outcome. PMID- 26138122 TI - Effect of Antibiotic Class on Stroke Outcome. AB - BACKGROUND AND PURPOSE: Infections are common after stroke and associated with worse outcome. Clinical trials evaluating the benefit of prophylactic antibiotics have produced mixed results. This study explores the possibility that antibiotics of different classes may differentially affect stroke outcome. METHODS: Lewis rats were subjected to transient cerebral ischemia (2 hours) and survived for 1 month. The day after stroke they were randomized to therapy with ceftiofur (a beta-lactam antibiotic), enrofloxacin (a fluoroquinolone antibiotic), or vehicle (as controls) and underwent the equivalent of 7 days of treatment. Behavioral tests were performed weekly until euthanization. In a subset of animals, histology was done. RESULTS: There were no differences in outcomes at 24 hours or 1 week after stroke among the different groups. At 1 month after stroke, however, performance on the rotarod was worse in enrofloxacin-treated animals when compared with control animals. CONCLUSIONS: Independent of infection, the antibiotic enrofloxacin was associated with worse stroke outcome. These data echo the clinical observations to date and suggest that the secondary effects of antibiotics on stroke outcome should be considered when treating infection in subjects with stroke. The mechanism by which this antibiotic affects outcome needs to be elucidated. PMID- 26138123 TI - Chronic Kidney Disease in Patients With Lacunar Stroke: Association With Enlarged Perivascular Spaces and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease. AB - BACKGROUND AND PURPOSE: The relationship between chronic kidney disease and cerebral small vessel disease (cSVD), especially enlarged perivascular spaces (EPVS), has not been fully understood. This study aimed to investigate the association of chronic kidney disease and EPVS, as well as the total burden of cSVD on magnetic resonance imaging, expressed by the simultaneous presence of multiple markers of cSVD, among patients with first-ever lacunar stroke. METHODS: Four hundred and thirteen consecutive patients were prospectively enrolled. Centrum semiovale and basal ganglia EPVS on T2-weighted magnetic resonance imaging, as well as other imaging markers of cSVD, including lacune, white matter lesions, and cerebral microbleeds, were rated using validated scales. Chronic kidney disease was defined as either reduced estimated glomerular filtration rate or the presence of proteinuria. RESULTS: After adjustments for potential confounders by logistic regression, proteinuria and impaired estimated glomerular filtration rate were correlated with the severity of EPVS in both centrum semiovale (odds ratio [OR] 2.59; 95% confidence interval [CI] 1.19-5.64 and OR 2.37; 95% CI 1.19-4.73) and basal ganglia (OR 5.12; 95% CI 2.70-12.10 and OR 4.17; 95% CI 2.08-8.37). A similar association was also found between proteinuria and low estimated glomerular filtration rate levels and the comprehensive cSVD burden (OR 2.13; 95% CI 1.10-4.14 and OR 5.59; 95% CI 2.58-12.08). CONCLUSIONS: Proteinuria and impaired estimated glomerular filtration rate are associated with increasing EPVS severity and, furthermore, accumulated magnetic resonance imaging burden of cSVD in patients with first-ever acute lacunar stroke. PMID- 26138124 TI - Letter by Hsieh and Lin Regarding Article, "Acute Reperfusion Therapy and Stroke Care in Asia After Successful Endovascular Trials". PMID- 26138126 TI - Response to Letter Regarding Article, "Acute Reperfusion Therapy and Stroke Care in Asia After Successful Endovascular Trials". PMID- 26138125 TI - Impact of General Anesthesia on Safety and Outcomes in the Endovascular Arm of Interventional Management of Stroke (IMS) III Trial. AB - BACKGROUND AND PURPOSE: General anesthesia (GA) for endovascular therapy (EVT) of acute ischemic stroke may be associated with worse outcomes. METHODS: The Interventional Management of Stroke III trial randomized patients within 3 hours of acute ischemic stroke onset to intravenous tissue-type plasminogen activator+/ EVT. GA use within 7 hours of stroke onset was recorded per protocol. Good outcome was defined as 90-day modified Rankin Scale <=2. A multivariable analysis adjusting for dichotomized National Institutes of Health Stroke Scale (NIHSS; 8 19 versus >=20), age, and time from onset to groin puncture was performed. RESULTS: Four hundred thirty-four patients were randomized to EVT, 269 (62%) were treated under local anesthesia and 147 (33.9%) under GA; 18 (4%) were undetermined. The 2 groups were comparable except for median baseline NIHSS (16 local anesthesia versus 18 GA; P<0.0001). The GA group was less likely to achieve a good outcome (adjusted relative risk, 0.68; confidence interval, 0.52-0.90; P=0.0056) and had increased in-hospital mortality (adjusted relative risk, 2.84; confidence interval, 1.65-4.91; P=0.0002). Those with medically indicated GA had worse outcomes (adjusted relative risk, 0.49; confidence interval, 0.30-0.81; P=0.005) and increased mortality (relative risk, 3.93; confidence interval, 2.18 7.10; P<0.0001) with a trend for higher mortality with routine GA. There was no significant difference in the adjusted risks of subarachnoid hemorrhage (P=0.32) or symptomatic intracerebral hemorrhage (P=0.37). CONCLUSIONS: GA was associated with worse neurological outcomes and increased mortality in the EVT arm; this was primarily true among patients with medical indications for GA. Relative risk estimates, though not statistically significant, suggest reduced risk for subarachnoid hemorrhage and symptomatic intracerebral hemorrhage under local anesthesia. Although the reasons for these associations are not clear, these data support the use of local anesthesia when possible during EVT. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424. PMID- 26138127 TI - Response to Letter Regarding Article, "Prognostications of Fibrillations". PMID- 26138129 TI - Stroke Literature Synopses: Basic Science. PMID- 26138128 TI - Macrophage-Inducible C-Type Lectin/Spleen Tyrosine Kinase Signaling Pathway Contributes to Neuroinflammation After Subarachnoid Hemorrhage in Rats. AB - BACKGROUND AND PURPOSE: Macrophage-inducible C-type lectin (Mincle, CLEC4E) receptor is reported involved in neuroinflammation in cerebral ischemia and traumatic brain injury. This study was designed to investigate the role of Mincle and its downstream spleen tyrosine kinase (Syk) signal pathway in early brain injury after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Two hundred fifteen male Sprague-Dawley rats (280-320 g) were subjected to endovascular perforation model of SAH. SAH grade, neurological score, and brain water content were measured at 24 hours after SAH. Mincle/Syk, as well as CARD9 (a member of the caspase-associated recruitment domain [CARD], involved in innate immune response), interleukin-1beta,and myeloperoxidase expressions were analyzed by Western blot at 24 hours after SAH. Specific cell types that expressed Mincle were detected with double immunofluorescence staining. Mincle small interfering RNA, recombinant SAP130, and a selective Syk phosphorylation inhibitor piceatannol were used for intervention. RESULTS: Brain water content increased and neurological functions decreased in rats after SAH. The expression of SAP130, Mincle, Syk, and p-Syk increased at 12 hours and peaked at 24 hours after SAH. Mincle small interfering RNA reduced interleukin-1beta and infiltration of myeloperoxidase positive cells, decreased brain water content, and improved neurological functions at 24 hours after SAH. Recombinant SAP130 upregulated the expression of p-Syk and CARD9 and increased the levels of interleukin-1beta and myeloperoxidase, even though it did not increase brain water content nor it deteriorated neurological function at 24 hours after SAH. Syk inhibitor piceatannol reduced brain edema at 24 hours after SAH. CONCLUSION: Mincle/Syk is involved in early brain injury after SAH, and they may serve as new targets for therapeutic intervention. PMID- 26138131 TI - Effects of stereoelectronic interactions on the relativistic spin-orbit and paramagnetic components of the (13)C NMR shielding tensors of dihaloethenes. AB - In this study, stereoelectronic interactions were considered to explain the experimental difference in the magnitude of the known heavy-atom effect on the (13)C NMR chemical shifts in cis- and trans-1,2-dihaloethene isomers (halo = F, Cl, Br or I). The experimental values were compared to the calculated values with various DFT functionals using both the nonrelativistic approach (NR) and the relativistic approximations SR-ZORA (SR) and SO-ZORA (SO). NBO and NLMO contributions to the (13)C NMR shielding tensors were determined to assess which stereoelectronic interactions have a more important effect on the shielding tensor in each principal axis system (PAS) coordinate. These analyses associated with the orbital rotation model and the HOMO-LUMO energy gap enable rationalization of trends between cis and trans isomers from fluorine to iodine derivatives. Both paramagnetic and SO shielding terms were responsible for the observed trends. It was possible to conclude that the steric interactions between the two iodine atoms and the hyperconjugative interactions involving the halogen lone pairs (LP(X)) and piC[double bond, length as m-dash]C*, sigmaC[double bond, length as m-dash]C* and sigmaC-X* antibonding orbitals are responsible for the lower (13)C NMR shielding for the cis isomers of the bromine and the iodine compounds than that of the trans isomers. PMID- 26138130 TI - Adopting a Patient-Centered Approach to Primary Outcome Analysis of Acute Stroke Trials Using a Utility-Weighted Modified Rankin Scale. AB - BACKGROUND AND PURPOSE: Although the modified Rankin Scale (mRS) is the most commonly used primary end point in acute stroke trials, its power is limited when analyzed in dichotomized fashion and its indication of effect size challenging to interpret when analyzed ordinally. Weighting the 7 Rankin levels by utilities may improve scale interpretability while preserving statistical power. METHODS: A utility-weighted mRS (UW-mRS) was derived by averaging values from time-tradeoff (patient centered) and person-tradeoff (clinician centered) studies. The UW-mRS, standard ordinal mRS, and dichotomized mRS were applied to 11 trials or meta analyses of acute stroke treatments, including lytic, endovascular reperfusion, blood pressure moderation, and hemicraniectomy interventions. RESULTS: Utility values were 1.0 for mRS level 0; 0.91 for mRS level 1; 0.76 for mRS level 2; 0.65 for mRS level 3; 0.33 for mRS level 4; 0 for mRS level 5; and 0 for mRS level 6. For trials with unidirectional treatment effects, the UW-mRS paralleled the ordinal mRS and outperformed dichotomous mRS analyses. Both the UW-mRS and the ordinal mRS were statistically significant in 6 of 8 unidirectional effect trials, whereas dichotomous analyses were statistically significant in 2 to 4 of 8. In bidirectional effect trials, both the UW-mRS and ordinal tests captured the divergent treatment effects by showing neutral results, whereas some dichotomized analyses showed positive results. Mean utility differences in trials with statistically significant positive results ranged from 0.026 to 0.249. CONCLUSIONS: A UW-mRS performs similar to the standard ordinal mRS in detecting treatment effects in actual stroke trials and ensures the quantitative outcome is a valid reflection of patient-centered benefits. PMID- 26138132 TI - Therapeutic drug monitoring is predictive of loss of response after de-escalation of infliximab therapy in patients with inflammatory bowel disease in clinical remission. AB - BACKGROUND: There is no evidence that therapeutic drug monitoring is helpful in patients with inflammatory bowel disease patients in clinical remission with infliximab therapy. METHODS: Eighty consecutive inflammatory bowel disease patients in clinical remission on infliximab maintenance therapy were included and followed-up for at least one year. Infliximab trough level and antibody to infliximab concentration were measured prior to enrollment. At the time of enrollment, physicians in charge were free to alleviate infliximab therapy. Discrepancies between blind and therapeutic drug monitoring-based adjustments were assessed at the end of the follow-up period. Relapse-free survival was analyzed using univariate and multivariate analyses. RESULTS: The mean infliximab trough level was 3.1 MUg/mL. Antibody to infliximab was found in 15 (19%) patients. At the end of the follow-up period, 18 (22.5%) patients experienced a relapse. The 3, 6, 9 and 12-month relapse-free rates were 98%, 87%, 86% and 80%, respectively. In our multivariate analysis, relapse-free survival was negatively associated with discrepancies between therapeutic drug monitoring-based and blind adjustments of infliximab therapy, absence of concomitant immunomodulator, the absence of mucosal healing, prior use of infliximab, infliximab therapy duration>2 years and C-reactive protein levels>5mg/L at the time of enrollment. CONCLUSION: In patients with inflammatory bowel disease in clinical remission on infliximab therapy, de-escalation of infliximab therapy should be considered based on therapeutic drug monitoring rather than according to symptoms and CRP. PMID- 26138133 TI - Efficacy of intravenous immunoglobulin therapy in giant cell hepatitis with autoimmune hemolytic anemia: A multicenter study. AB - BACKGROUND AND OBJECTIVE: Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare disease of infancy, of possible autoimmune mechanism with poor prognosis due to its scarce response to immunosuppressive drugs. The aim of this retrospective multicenter study was to evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) treatment in inducing and maintaining remission of the liver disease, in patients with GCH-AHA. METHODS: Seven children with GCH AHA, four newly diagnosed, and three in relapse, being treated with different therapies, received one to three IVIg infusions (0.5 to 2g/kg) in association with other immunosuppressive drugs. Subsequently five of them received monthly sequential IVIg infusions (mean 13.4, range 7-24). RESULTS: IVIg infusions as first-line therapy associated with prednisone and other immunosuppressive drugs significantly (P=0.04) reduced the aminotransferase activity in all patients and normalized prothrombin activity in the only patient with severe liver dysfunction. Sequential monthly IVIg infusions determined a steroid-sparing effect and allowed a complete or partial remission in all patients, although with temporary efficacy, since relapse of the hemolytic anemia and/or of liver disease occurred in all patients. IVIg infusions were associated with mild side effects in two patients. CONCLUSIONS: IVIg infusion can be safely and effectively administered in patients with severe GCH-AHA at diagnosis, or in case of relapse, in association with other immunosuppressive drugs. Repeated IVIg infusions may help maintain remission, however, due to their temporary efficacy, they should not be routinely employed. PMID- 26138134 TI - Antibacterial activity of chlorhexidine after final irrigation with ethanol: CLSM and culture-based method analysis. AB - This study investigated the effect of 95% ethanol on the antibacterial properties of 2% chlorexidine (CHX) over monospecies biofilm (Enterococcus faecalis) through a culture-based method, and over multispecies biofilm using confocal laser scanning microscopy (CLSM). For monospecies model, E. faecalis biofilm was induced in 40 root canals. The irrigation procedures were: S-saline solution; S/CHX-saline solution + CHX; E-ethanol; and E/CHX-ethanol + CHX. Microbial sampling was performed at three periods: before (S1), immediately after (S2), and 72 h after the final flush (S3). For multispecies biofilm model, 28 sterilized bovine dentin blocks were fixed on a removable orthodontic device to allow intraoral biofilm development. Seven samples were used in each group. Statistical analysis was carried out by using the Kruskal-Wallis test and Dunn's test for multiple comparisons. There was a significant reduction in CFUs count immediately after the final flush (S2) in all experimental groups (P < 0.05). However, only S/CHX, E and E/CHX groups had CFU counts close to zero, without differences among them (P > 0.05). After 72h (S3), the S/CHX and E/CHX groups had CFU counts near zero (P > 0.05). The CFU count increased in S3 for S and E groups (P < 0.05). CLSM showed that the percentages of remaining live cells were similar in S/CHX, E, and E/CHX groups (P > 0.05). The S group had the highest percentage of live cells (P < 0.05). The 95% ethanol did not interfere in the antibacterial properties of 2% CHX over mono- and multispecies biofilms. PMID- 26138135 TI - Acid-Base Pairs in Lewis Acidic Zeolites Promote Direct Aldol Reactions by Soft Enolization. AB - Hf-, Sn-, and Zr-Beta zeolites catalyze the cross-aldol condensation of aromatic aldehydes with acetone under mild reaction conditions with near quantitative yields. NMR studies with isotopically labeled molecules confirm that acid-base pairs in the Si-O-M framework ensemble promote soft enolization through alpha proton abstraction. The Lewis acidic zeolites maintain activity in the presence of water and, unlike traditional base catalysts, in acidic solutions. PMID- 26138136 TI - Complications in Stent-Assisted Endovascular Therapy of Ruptured Intracranial Aneurysms and Relevance to Antiplatelet Administration: A Systematic Review. AB - BACKGROUND AND PURPOSE: Despite the increasing use of stent-assisted coiling for ruptured intracranial aneurysms, there is little consensus regarding the appropriate antiplatelet administration for this. The objectives of this systematic review were to provide an overview of complications and their association with the method of antiplatelet administration in stent-assisted coiling for ruptured intracranial aneurysms. MATERIALS AND METHODS: A comprehensive search of the literature in the data bases was conducted to identify studies reporting complications of stent-assisted coiling for ruptured intracranial aneurysms. The pooled event rate of preprocedural thromboembolisms, hemorrhages, and mortality was estimated from the selected studies. Subgroup analyses were performed by the method of antiplatelet administration (pre-, postprocedural, and modified). Meta-analysis was conducted to compare periprocedural complications and mortality between ruptured intracranial aneurysms and unruptured intracranial aneurysms. RESULTS: Of the 8476 studies identified, 33 with 1090 patients were included. The event rates of thromboembolism and intra- and postprocedural hemorrhage were 11.2% (95% CI, 9.2% 13.6%), 5.4% (95% CI, 4.1%-7.2%), and 3.6% (95% CI, 2.6%-5.1%), respectively. Subgroup analyses of thromboembolism showed a statistically significant difference between groups (P < .05). In the preprocedural and modified antiplatelet groups, the risk for thromboembolism in stent-assisted coiling for ruptured intracranial aneurysm was not significantly different from that for unruptured intracranial aneurysm, though this risk of the postprocedural antiplatelet group was significantly higher in ruptured intracranial aneurysms than in unruptured intracranial aneurysms. CONCLUSIONS: On the basis of current evidence, complications of stent-assisted coiling for ruptured intracranial aneurysm may be affected by the method of antiplatelet administration. PMID- 26138137 TI - Injury to the Cerebellum in Term Asphyxiated Newborns Treated with Hypothermia. AB - BACKGROUND AND PURPOSE: Until now, most studies of brain injury related to term neonatal encephalopathy have focused on the cerebrum and ignored the cerebellum. We sought to evaluate whether cerebellar injury occurs in term asphyxiated neonates. MATERIALS AND METHODS: Asphyxiated neonates treated with hypothermia were enrolled prospectively. Severity of brain injury in the cerebrum was scored on each MR imaging obtained during the first month of life; cerebellar injury was recorded when mentioned in the imaging or autopsy report. In addition, for some of the neonates, the ADC and fractional anisotropy were measured in 4 regions of interest in the cerebellum. RESULTS: One hundred seventy-two asphyxiated neonates met the criteria for hypothermia. Cerebellar injury was visible only on conventional imaging of 4% of the neonates for whom brain imaging was available, but it was reported in the autopsy report of 72% of the neonates who died. In addition, 41 of the asphyxiated neonates had a total of 84 ADC and fractional anisotropy maps. Neonates with brain injury described only in the cerebrum demonstrated ADC and fractional anisotropy changes similar to those of the neonates with brain injury in the cerebrum and cerebellum--increased ADC around day 10 of life and decreased fractional anisotropy on day 2-3 of life, around day 10 of life, and around 1 month of age. CONCLUSIONS: The cerebellum may be injured in term neonates after birth asphyxia. These cerebellar injuries are only rarely visible on conventional imaging, but advanced neuroimaging techniques may help to identify them. PMID- 26138138 TI - Radiation Necrosis in Pediatric Patients with Brain Tumors Treated with Proton Radiotherapy. AB - BACKGROUND AND PURPOSE: Proton radiotherapy has been increasingly utilized to treat pediatric brain tumors, however, limited information exists regarding radiation necrosis among these patients. Our aim was to evaluate the incidence, timing, clinical significance, risk factors, and imaging patterns of radiation necrosis in pediatric patients with brain tumors treated with proton radiation therapy. MATERIALS AND METHODS: A retrospective study was performed on 60 consecutive pediatric patients with primary brain tumors treated with proton radiation therapy. Radiation necrosis was assessed by examining serial MRIs and clinical records to determine the incidence, timing, risk factors, imaging patterns, and clinical significance associated with the development of radiation necrosis in these patients. Radiation necrosis was defined as areas of new enhancement within an anatomic region with previous exposure to proton beam therapy with subsequent decrease on follow-up imaging without changes in chemotherapy. RESULTS: Thirty-one percent of patients developed radiation necrosis with a median time to development of 5.0 months (range, 3-11 months). Risk factors included multiple chemotherapy agents (>3 cytotoxic agents) and atypical teratoid rhabdoid tumor pathology (P = .03 and P = .03, respectively). The most common imaging patterns were small (median, 0.9 cm) and multifocal (63% of patients) areas of parenchymal enhancement remote from the surgical site. The median time to complete resolution on imaging was 5.3 months (range, 3-12 months). Among patients with imaging findings of radiation necrosis, 25% demonstrated severe symptoms with medical intervention indicated. CONCLUSIONS: Pediatric patients with brain tumors treated with proton radiation therapy demonstrate a high incidence of radiation necrosis and a short time to development of necrosis. Multiple small areas of necrosis are frequently identified on imaging. Exposure to multiple chemotherapy agents was a significant risk factor associated with radiation necrosis in these patients. PMID- 26138139 TI - Intrasaccular Flow Disruption in Acutely Ruptured Aneurysms: A Multicenter Retrospective Review of the Use of the WEB. AB - BACKGROUND AND PURPOSE: Use of the WEB intra-aneurysmal flow-disruption device in unruptured wide-neck bifurcation aneurysms has proven safety and efficacy. However, ruptured aneurysms are underrepresented in existing studies. This retrospective multicenter study describes the use of the WEB in patients with a ruptured intracranial aneurysm. MATERIALS AND METHODS: Ten centers contributed to this study. Clinical and procedural data of 47 patients with 52 aneurysms were analyzed retrospectively together with follow-up angiographies. RESULTS: There were 37 anterior and 15 posterior circulation aneurysms with a neck size of >=4 mm in 49 of 52 (94%) aneurysms; 45 (87%) aneurysms were <10 mm, and 2 were partially thrombosed. Successful placement of the WEB was possible in every case. Adjunctive devices were used in 8 of 52 (15%) aneurysms. Thromboembolic events were observed in 4 of 52 (8%) patients. Adverse events occurred in 15 patients with 16 aneurysms, 9 of which were potentially related to the WEB procedure (3 thromboembolic events, 5 protrusions, and 1 perforations; 2 perforations were caused by the wire or catheter), but none had a clinical impact. Four patients were retreated. Short-term follow-up in 25 of 39 patients revealed complete occlusion in 15 of 25 (60%), 5 of 25 (20%) with residual neck, and 5 of 25 (20%) with residual aneurysm filling. Short- to midterm imaging in 9 of 25 patients revealed complete occlusion in 5 (55.6%), residual neck in 2 (22%), and residual aneurysm filling in 2 (22%). Of 47 patients, 23 (49%) had an mRS score of 0, 1, or 2; 13 (28%) had an mRS score of 3 or 4; and none had an mRS score of 5 at discharge. CONCLUSIONS: This retrospective series showed good procedural safety, feasibility, and stability of midterm occlusion in ruptured wide-neck bifurcation aneurysms. PMID- 26138140 TI - Cytotoxic Edema in Posterior Reversible Encephalopathy Syndrome: Correlation of MRI Features with Serum Albumin Levels. AB - BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome is a clinicoradiologic entity with typical MR imaging showing predominant vasogenic and occasional cytotoxic edema. It is unclear whether MR imaging correlates with levels of serum albumin. We determined potential risk factors for development of cytotoxic edema in posterior reversible encephalopathy syndrome. MATERIALS AND METHODS: Seventy-nine cases with typical clinical symptoms and characteristic neuroradiologic findings conformed to posterior reversible encephalopathy syndrome diagnostic criteria and were included in this study. FLAIR, DWI, and ADC maps were interpreted to evaluate the severity and type of edema. MR imaging was correlated with the levels of serum albumin, and cytotoxic edema was compared with the location and severity of brain edema. RESULTS: Pure vasogenic edema was found in 53 cases (67.09%), and vasogenic edema complicated with cytotoxic components, in 26 patients (32.91%). There was no difference in serum albumin levels between patients with cytotoxic components and those with vasogenic edema (P = .983). There was a significant difference in the edema scale scores between patients with cytotoxic edema and those with vasogenic edema (P = .006). The percentage of cytotoxic edema located in the area with higher scale scores of edema was significantly larger than that in areas with lower scale scores of edema (P = .002). CONCLUSIONS: Serum albumin may contribute to the development of edema in PRES but is not a decisive factor for edema type. Cytotoxic edema in posterior reversible encephalopathy syndrome is probably related to regional decreased perfusion and arteriolopathy. Further work should be undertaken to discover the pathophysiologic mechanisms involved. PMID- 26138141 TI - Public health, universal health coverage, and Sustainable Development Goals: can they coexist? PMID- 26138144 TI - Should We Use Antibiotic Prophylaxis for Flexible Cystoscopy? A Systematic Review and Meta-Analysis. AB - INTRODUCTION: The role of antibiotic prophylaxis for routine flexible cystoscopy (FC) is not clear due to the varying practices of individual clinicians. There are no formal guidelines, and this may be due to a lack of formal summary of the data. METHODS: A systematic review was conducted in April 2014 including all randomised control trials on prophylactic antibiotic use for FC. The main outcome measures were confirmed bacteriuria on mid-stream urine (MSU), asymptomatic bacteriuria and symptomatic bacteriuria. A meta-analysis was conducted with difference between groups expressed as an odds ratio (OR) and control group risk. RESULTS: 5,107 patients were included, 2,173 in placebo and 2,934 in the antibiotic group. The OR for all three outcomes favoured the antibiotic group; the risk of developing symptomatic bacteriuria was 0.06 times more likely in the control group (OR 0.34), 0.054 (OR 0.40) for developing asymptomatic bacteriuria and 0.109 for confirming bacteriuria on MSU (OR 0.36). The number needed to treat (NNT) was 15 (13-19) for MSU positive bacteriuria; 32 (27-42) for symptomatic bacteriuria and 26 (23-33) for asymptomatic bacteriuria. CONCLUSIONS: Antibiotic prophylaxis did confer a reduction in cases of symptomatic and asymptomatic bacteriuria but the NNT were high. Therefore, the authors cannot advocate the use of antibiotic prophylaxis for routine FC procedures. PMID- 26138143 TI - Structural basis for catalytically restrictive dynamics of a high-energy enzyme state. AB - An emerging paradigm in enzymology is that transient high-energy structural states play crucial roles in enzymatic reaction cycles. Generally, these high energy or 'invisible' states cannot be studied directly at atomic resolution using existing structural and spectroscopic techniques owing to their low populations or short residence times. Here we report the direct NMR-based detection of the molecular topology and conformational dynamics of a catalytically indispensable high-energy state of an adenylate kinase variant. On the basis of matching energy barriers for conformational dynamics and catalytic turnover, it was found that the enzyme's catalytic activity is governed by its dynamic interconversion between the high-energy state and a ground state structure that was determined by X-ray crystallography. Our results show that it is possible to rationally tune enzymes' conformational dynamics and hence their catalytic power--a key aspect in rational design of enzymes catalysing novel reactions. PMID- 26138142 TI - Impaired protein translation in Drosophila models for Charcot-Marie-Tooth neuropathy caused by mutant tRNA synthetases. AB - Dominant mutations in five tRNA synthetases cause Charcot-Marie-Tooth (CMT) neuropathy, suggesting that altered aminoacylation function underlies the disease. However, previous studies showed that loss of aminoacylation activity is not required to cause CMT. Here we present a Drosophila model for CMT with mutations in glycyl-tRNA synthetase (GARS). Expression of three CMT-mutant GARS proteins induces defects in motor performance and motor and sensory neuron morphology, and shortens lifespan. Mutant GARS proteins display normal subcellular localization but markedly reduce global protein synthesis in motor and sensory neurons, or when ubiquitously expressed in adults, as revealed by FUNCAT and BONCAT. Translational slowdown is not attributable to altered tRNA(Gly) aminoacylation, and cannot be rescued by Drosophila Gars overexpression, indicating a gain-of-toxic-function mechanism. Expression of CMT mutant tyrosyl-tRNA synthetase also impairs translation, suggesting a common pathogenic mechanism. Finally, genetic reduction of translation is sufficient to induce CMT-like phenotypes, indicating a causal contribution of translational slowdown to CMT. PMID- 26138145 TI - Increased anatomical precision of pre-surgical intracranial mapping by combining white matter tractography with direct cortical stimulation. PMID- 26138146 TI - Multi-scale analysis of neural activity in humans: Implications for micro-scale electrocorticography. AB - OBJECTIVE: Electrocorticography grids have been used to study and diagnose neural pathophysiology for over 50 years, and recently have been used for various neural prosthetic applications. Here we provide evidence that micro-scale electrodes are better suited for studying cortical pathology and function, and for implementing neural prostheses. METHODS: This work compares dynamics in space, time, and frequency of cortical field potentials recorded by three types of electrodes: electrocorticographic (ECoG) electrodes, non-penetrating micro-ECoG (MUECoG) electrodes that use microelectrodes and have tighter interelectrode spacing; and penetrating microelectrodes (MEA) that penetrate the cortex to record single- or multiunit activity (SUA or MUA) and local field potentials (LFP). RESULTS: While the finest spatial scales are found in LFPs recorded intracortically, we found that LFP recorded from MUECoG electrodes demonstrate scales of linear similarity (i.e., correlation, coherence, and phase) closer to the intracortical electrodes than the clinical ECoG electrodes. CONCLUSIONS: We conclude that LFPs can be recorded intracortically and epicortically at finer scales than clinical ECoG electrodes are capable of capturing. SIGNIFICANCE: Recorded with appropriately scaled electrodes and grids, field potentials expose a more detailed representation of cortical network activity, enabling advanced analyses of cortical pathology and demanding applications such as brain-computer interfaces. PMID- 26138147 TI - Identification of epileptic high frequency oscillations in the time domain by using MEG beamformer-based virtual sensors. AB - OBJECTIVE: High frequency oscillations (HFOs, >80Hz) are biomarkers for epileptogenic cortex in invasive and non-invasive electroencephalography (EEG). Identification of HFOs in magnetoencephalography (MEG) is hindered by noise. Computing spatial filters using beamforming to reconstruct time series for selected brain regions, so-called virtual sensors (VS), can increase the signal to-noise ratio. We identified HFOs in MEG in time domain using VS. METHODS: Fifteen minutes of MEG data were selected from 12 patients. VS were placed around the epileptic spikes (affected region) and in the contralateral hemisphere. VS and physical sensors were reviewed for HFOs and spikes. HFO locations were compared to spikes and other clinical parameters. RESULTS: Eight patients showed 78 time points with 575 HFOs in VS, 513 were in the affected region. HFOs could not be identified in physical sensors for 61 of the 78 VS time points. HFOs overlapped with presumed epileptogenic areas and were also visible in unfiltered VS signals. CONCLUSION: Beamformer-based VS analysis can help to identify epileptic HFOs that are not discernable in physical MEG sensors. SIGNIFICANCE: This approach can be extended to enable localization of non-invasively recorded HFOs. This would help surgical planning and reduce the need for invasive diagnostics. PMID- 26138148 TI - The effect of multimodal and enriched feedback on SMR-BCI performance. AB - OBJECTIVE: This study investigated the effect of multimodal (visual and auditory) continuous feedback with information about the uncertainty of the input signal on motor imagery based BCI performance. A liquid floating through a visualization of a funnel (funnel feedback) provided enriched visual or enriched multimodal feedback. METHODS: In a between subject design 30 healthy SMR-BCI naive participants were provided with either conventional bar feedback (CB), or visual funnel feedback (UF), or multimodal (visual and auditory) funnel feedback (MF). Subjects were required to imagine left and right hand movement and were trained to control the SMR based BCI for five sessions on separate days. RESULTS: Feedback accuracy varied largely between participants. The MF feedback lead to a significantly better performance in session 1 as compared to the CB feedback and could significantly enhance motivation and minimize frustration in BCI use across the five training sessions. CONCLUSION: The present study demonstrates that the BCI funnel feedback allows participants to modulate sensorimotor EEG rhythms. Participants were able to control the BCI with the funnel feedback with better performance during the initial session and less frustration compared to the CB feedback. SIGNIFICANCE: The multimodal funnel feedback provides an alternative to the conventional cursorbar feedback for training subjects to modulate their sensorimotor rhythms. PMID- 26138149 TI - Autonomic dysfunction in clinically isolated syndrome suggestive of multiple sclerosis. AB - OBJECTIVES: The aim of this study was to determine the extent of autonomic dysfunction in patients with clinically isolated syndrome (CIS) by using a standardized battery of autonomic tests in the form of the Composite Autonomic Scoring Scale (CASS). METHODS: This was a prospective, cross sectional study which included 24 consecutive patients who were diagnosed with CIS and 17 healthy controls. In all participants, heart rate and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing and blood pressure response to passive tilt were performed. In 16 patients, Quantitative Sudomotor Axon Reflex Test (QSART) and catecholamine measurement was performed. RESULTS: The proportion of CIS patients with pathological adrenergic index was statistically significantly higher compared to healthy controls (12 vs 2, p=0.018), while there was no difference in cardiovagal index between groups. Five patients had a sudomotor index of 1 (in 4 there was hypohydrosis <50% and in 1 persistent foot hyperhidrosis). When combining adrenergic, cardiovagal and sudomotor index into CASS, 8 patients (50%) had evidence of autonomic dysfunction, 7 mild and one moderate. CONCLUSION: Sympathetic nervous system is frequently affected in CIS patients. SIGNIFICANCE: CASS is able to detect autonomic nervous system dysfunction in CIS patients. PMID- 26138150 TI - Detection of Sarcocystis spp. infection in bobcats (Lynx rufus). AB - The protozoan Sarcocystis neurona is an important cause of severe clinical disease of horses (called equine protozoal myeloencephalitis, EPM), marine mammals, companion animals, and several species of wildlife animals in the Americas. The Virginia opossum (Didelphis virginiana) is its definitive host in the USA and other animals act as intermediate or aberrant hosts. Samples of tongue and heart from 35 bobcats hunted for fur and food from Mississippi State, USA in February, 2014 were used for the present study. Muscles were examined for Sarcocystis infection by microscopic examination of either unfixed muscle squash preparations or pepsin digests, by histopathology of fixed samples, and by molecular methods. Sarcocystis-like bradyzoites were found in digests of 14 hearts and 10 tongues of 35 bobcats. In histological sections, sarcocysts were found in 26 of 35 bobcats; all appeared relatively thin-walled similar to S. felis sarcocysts under light microscope at 1000* magnification. S. neurona-like sarcocysts having thickened villar tips were seen in unstained muscle squash of tongue of two bobcats and PCR-DNA sequencing identified them definitively as S. neurona-like parasites. DNA extracted from bradyzoites obtained from tongue and heart muscle digests was analyzed by PCR-DNA sequencing at the ITS1 locus. Results indicated the presence of S. neurona-like parasite in 26 of 35 samples. ITS1 sequences identical to S. dasypi were identified in 3 bobcats, 2 of which were also co-infected with S. neurona-like parasite. The high prevalence of sarcocysts in bobcat tissues suggested an efficient sylvatic cycle of Sarcocystis spp. in the remote regions of Mississippi State with the bobcat as a relevant intermediate host. PMID- 26138151 TI - Histological and immunohistochemical characterization of Hypoderma lineatum (Diptera: oestridae) warbles. AB - Hypoderma larvae are tissue invading parasites which spend several months migrating within the host tissues before completing their development in the sub dermal tissues of the back. Subcutaneous stages of the parasite produce an inflammatory reaction in the skin called "warbles", as well as holes through which larvae breathe. In order to elucidate the microscopical structure of the warbles, three hides from warbled cows were collected in a slaughterhouse in Lugo (NW, Spain) between March and May 2012. A total of 60 skin samples, including warbles at different phases of development, were chosen for histopathological and immunohistochemical examination. Microscopic lesions were classified into three groups, according to the predominance and distribution of different cell populations. In warbles containing living or recently dead larvae with apparently well preserved cuticle (type 1), plasma cells were observed in high number. However, macrophages and lymphocytes were the predominant cells in granulomas (type 2) formed in relation to remnants of the dead parasite, containing or not remains of the altered cuticle. Scars (type 3) were characterized by granulation tissue. Immunohistochemistry showed that B lymphocytes and IgG(+) cells were predominant in the lesions, as long as the cuticle of the larvae is intact. On the other side, CD3(+) lymphocytes increased once cuticle is destroyed and a granuloma is formed. Macrophages, revealed by CD68(+), MAC387(+) and lysozyme immunolabelling, were detected in all types of lesions, but they were more abundant in type 2 and scarce in scars. These cells appeared isolated around the intact larvae or forming aggregates around its remains in the granuloma. Moreover, a strong immunolabelling against MAC387 antibody was registered in the squamous epithelium covering the breathing pore. This finding may be associated with the expression of calprotectin, a molecule involved on the healing process of the skin after larvae outcome. Our results suggest the predominance of a humoral response inside the warble as long as larvae are intact. Once they are destroyed, cellular response occurred, isolating and destroying the remains of the larvae until healing process completes and scars with low numbers of inflammatory cells appear. PMID- 26138152 TI - Molecular epidemiological survey and genetic analysis of vector-borne infections of cattle in Luzon Island, the Philippines. AB - In the Philippines, vector-borne disease is one of the important problems in the livestock industry. To elucidate the epidemiology of vector-borne diseases in cattle on Luzon Island, the Philippines, the prevalence of five protozoan agents was assessed by polymerase chain reaction. Out of the 339 samples, 324 (95.5%), 154 (45.4%), 209 (61.6%), 140 (41.3%), and 2 (0.6%) were positive for Anaplasma marginale, Babesia bigemina, Babesia bovis, Theileria spp., and Trypanosoma evansi infections, respectively. Mixed infections were detected in 290 (85.5%) samples, of which 115 (33.9%) had two pathogens, 144 (42.5%) had three pathogens, and 31 (9.1%) had four kinds of pathogens. 16S rRNA gene was 100% identical in A. marginale compared with the same lineage across the world. B. bovis RAP-1 and B. bigemina AMA-1 genes were identical with 92.27%-100% and 97.07%-100% sequences, respectively, in the database (Asian isolates). MPSP genes of Theileria spp. were 83.51%-100% identical with the one another. Phylogenetic analysis showed that they belong to the groups of T. sergenti and T. buffeli. Positive rates of the tick-borne pathogens were extremely high in this area. These findings provide vital information that can be used for the planning and execution of effective control measures for vector-borne diseases in the Philippine cattle industry. PMID- 26138153 TI - Anthelmintics: The best way to predict the future is to create it. AB - 'The best way to predict the future is to create it.' When we look at drugs that are used to control parasites, we see that new knowledge has been created (discovered) about their modes of action. This knowledge will allow us to predict combinations of drugs which can be used together rationally to increase the spectrum of action and to slow the development of anthelmintic resistance. In this paper we comment on some recent observations of ours on the modes of action of emodepside, diethylcarbamazine and tribendimidine. Emodepside increases the activation of a SLO-1 K(+) current inhibiting movement, and diethylcarbamazine has a synergistic effect on the effect of emodepside on the SLO-1 K(+) current, increasing the size of the response. The combination may be considered for further testing for therapeutic use. Tribendimidine is a selective cholinergic nematode B-subtype nAChR agonist, producing muscle depolarization and contraction. It has different subtype selectivity to levamisole and may be effective in the presence of some types of levamisole resistance. The new information about the modes of action may aid the design of rational drug combinations designed to slow the development of resistance or increase the spectrum of action. PMID- 26138154 TI - Association between the traditional Chinese medicine pathological factors of opioid addiction and DRD2/ANKK1 TaqIA polymorphisms. AB - BACKGROUND: As we known, Traditional Chinese Medicine (TCM) helps to prevent the relapse of drug addiction. However, the scientific basis of TCM remains unclear because of limitations of current reductionist approaches. We aimed to explore the possible mechanism of how ANKK1 TaqIA (A1/A2) [rs1800497(T/C)] affects the relapse of opioid addiction on the perspective of Chinese traditional medicine. METHODS: The ANKK1 TaqIA (A1/A2) [rs1800497(T/C)] of the dopamine D2 receptor (DRD2) polymorphisms were genotyped in a case-control sample consisting of 347 opioid addicts and 155 healthy controls with RT-PCR and the TCM pathological factors were collected by means of Syndrome Elements Differentiation in the case control sample. RESULTS: DRD2/ANKK1 TaqIA Polymorphisms has no relation with opioid addiction relapse; but for those who were diagnosed with phlegm syndrome, DRD2/ANKK1 TaqIA Polymorphisms affect the replapse of apioid addiction (P < 0.05). CONCLUSIONS: DRD2/ANKK1 TaqIA is associated with opioid addict and it is obvious in opioid addicts who suffer from the phlegm syndrome. PMID- 26138155 TI - Role of the nitric oxide donor sodium nitroprusside in the antidepressant effect of ketamine in mice. AB - Ketamine may represent an efficient alternative antidepressant with rapid therapeutic onset; however, the clinical use of ketamine is hampered by psychosis like side-effects. Recent studies suggest that the nitric oxide (NO) donor sodium nitroprusside (SNP) prevents psychosis-like abnormalities triggered by ketamine or another NMDA receptor (NMDAR) antagonist, phencyclidine (PCP) in rats. SNP was shown to elicit antipsychotic effects also in humans. Considering the tight interrelation between NMDAR activation and neuronal NO synthesis, we evaluated the effect of pre-treatment with SNP on the antidepressant action of ketamine. We found that SNP (0.5-1mg/kg, i.p.) did not alter the antidepressant effect of ketamine (30 mg/kg) in the Porsolt Forced Swim Test (FST) in mice. Additionally, SNP by itself produced no effect in the FST or in the openfield. This suggests indirectly a differential involvement of the nitrinergic system in the antidepressant vs. psychotomimetic effect of ketamine, although an influence of species-specific differences cannot be excluded in this interpretation. PMID- 26138156 TI - Restricted mobility of side chains on concave surfaces of solenoid proteins may impart heightened potential for intermolecular interactions. AB - Significant progress has been made in the determination of the protein structures with their number today passing over a hundred thousand structures. The next challenge is the understanding and prediction of protein-protein and protein ligand interactions. In this work we address this problem by analyzing curved solenoid proteins. Many of these proteins are considered as "hub molecules" for their high potential to interact with many different molecules and to be a scaffold for multisubunit protein machineries. Our analysis of these structures through molecular dynamics simulations reveals that the mobility of the side chains on the concave surfaces of the solenoids is lower than on the convex ones. This result provides an explanation to the observed preferential binding of the ligands, including small and flexible ligands, to the concave surface of the curved solenoid proteins. The relationship between the landscapes and dynamic properties of the protein surfaces can be further generalized to the other types of protein structures and eventually used in the computer algorithms, allowing prediction of protein-ligand interactions by analysis of protein surfaces. PMID- 26138157 TI - One good hand. PMID- 26138158 TI - Physician attitudes toward shared decision making: A systematic review. AB - OBJECTIVE: Although evidence suggests that shared decision-making (SDM) can improve patient outcomes, uptake to date has been sparse. The purpose of this review was to determine the reported opinions of physicians regarding the use of SDM in clinical practice and to identify strategies to promote uptake. METHODS: We conducted a systematic review, including papers published between 2007 and 2014. RESULTS: The electronic search yielded 11,761 results. Following abstract review, 123 papers were selected for full text review, and 43 papers were included for analysis. Fourteen of the included studies considered SDM within the context of primary care, 25 in secondary care, and 4 in both. CONCLUSIONS: Physicians express positive attitudes toward SDM in clinical practice, although the level of support varies by clinical scenario, treatment decision and patient characteristics. PRACTICE IMPLICATIONS: Physician support for SDM is a necessary, if not sufficient, condition to facilitate meaningful SDM. In order to garner support for SDM, additional empirical evidence regarding the clinical and patient important outcomes must be established. Based on the results of this review, the authors suggest assessing the impact of SDM within the context of chronic disease management where multiple therapeutic options exist, and outcomes may be measured long-term. PMID- 26138159 TI - Apologies following an adverse medical event: The importance of focusing on the consumer's needs. AB - OBJECTIVE: The lack of a theoretical framework limits educators' ability to train health practitioners how to disclose, and apologise for adverse medical events. The multidimensional theory of apology proposes apologies consist of one or more components which can either be self-focused (focused on the apologiser's needs) or other-focused (focused on the needs of the consumer). We investigated whether the inclusion of other-focused elements in an apology enhanced its impact in a health setting. METHODS: 251 participants responded to a video-recording of an actor portraying a surgeon apologising to a patient for an adverse event. In one condition the apology was exclusively self-focused and in the other it was both self and other-focused. RESULTS: The self-focused apology was viewed more positively than negatively, but the apology that included additional other focused elements elicited a more favourable reaction; it was seen as more sincere and as denoting more sorriness. CONCLUSION AND PRACTICE IMPLICATIONS: Practitioners can enhance the impact of their apologies by including other focused elements, that is, demonstrate they understand the impact the event had on the consumers, express remorse for causing harm, and offer, or take action, to address the intangible harm caused. PMID- 26138160 TI - Care integration for endocrine disorders in cancer survivors. PMID- 26138161 TI - Does midlife obesity really lower dementia risk? PMID- 26138162 TI - Does midlife obesity really lower dementia risk? PMID- 26138163 TI - Does midlife obesity really lower dementia risk? PMID- 26138164 TI - Does midlife obesity really lower dementia risk? PMID- 26138165 TI - Does midlife obesity really lower dementia risk? PMID- 26138166 TI - Does midlife obesity really lower dementia risk? PMID- 26138167 TI - Does midlife obesity really lower dementia risk? - Authors' reply. PMID- 26138168 TI - Diabetes prevention in England. PMID- 26138169 TI - Diabetes prevention in England - Authors' reply. PMID- 26138170 TI - Do we need to change the medical curriculum: regarding the pain of others. AB - The current curriculum is behind its time and urgently requires to be reformed. The changes required are not only in the amount and type of desired information but also in the way this knowledge is acquired. Further, literature, art and philosophy require to be integrated in the curriculum so that a medical student can find his/her bearings in the society. Finally, but most importantly focus must be on developing empathy so that a prospective physician can correlate with the pain of patients and act towards relieving it rather than intellectualizing it. PMID- 26138171 TI - Renal denervation for the treatment of hypertension: If at first you don't succeed, try and try again. PMID- 26138172 TI - Resolute zotarolimus eluting stent for treatment of long coronary lesions. PMID- 26138174 TI - To see or not to see: An eye opening optical coherence tomography. PMID- 26138173 TI - Anaortic total arterial OPCAB - Panacea to all ills? PMID- 26138175 TI - Primary prevention of sudden cardiac death - Challenge the guidelines. AB - Primary Prevention of Sudden Cardiac death in post-infarction patients especially those with ejection fraction less than 35% is best achieved by implantable defibrillator. However, the cost of Quality Adjusted Life Years saved is $ 50,000 70,000, makes implantable defibrillators not an easily acceptable option when preventing SCD in a significant number of patients with low ejection fraction of 35 percent. In, addition excessive dependence on ejection fraction, excludes a large number of postinfarction patients with ejection fraction more than 35 percent, or patients with existing but not known heart disease. The two complementary strategies based on Public Health approach and Home AED approach and strengthening the program of Bystander CPR and AED application of publically available AED may be a better way for Primary Prevention of SCD in more number of patients. These approaches may be considered seriously to reduce sudden cardiac death in India, however, it needs to be proven. PMID- 26138176 TI - Renal sympathetic denervation using an externally irrigated radiofrequency ablation catheter for treatment of resistant hypertension - Acute safety and short term efficacy. AB - OBJECTIVES: This study was conducted to assess the acute safety and short term efficacy of renal sympathetic denervation (RSDN) using solid tip radiofrequency ablation (RFA) catheter and saline irrigation through the renal guiding catheter to achieve effective denervation. BACKGROUND: RSDN using a specialized solid-tip RFA catheter has recently been demonstrated to safely reduce systemic blood pressure in patients with refractory hypertension, the limitation being inadequate power delivery in renal arteries. So, we used solid-tip RFA catheter along with saline irrigation for RSDN. METHODS: Nine patients with resistant hypertension underwent CT and conventional renal angiography, followed by bilateral or unilateral RSDN using 5F RFA catheter with saline irrigation through renal guiding catheter. Repeat renal angiography was performed at the end of the procedure. In all patients, pre- and post-procedure serum creatinine was measured. RESULTS: Over 1-month period: 1) the systolic/diastolic blood pressure decreased by -57 +/- 20/-25 +/- 7.5 mm Hg; 2) all patients experienced a decrease in systolic blood pressure of at least -36 mm Hg (range 36-98 mm Hg); 3) there was no evidence of renal artery injury immediate post-procedure. There was no significant change in serum creatinine level. CONCLUSIONS: This data shows the acute procedural safety and short term efficacy of RSDN using modified externally irrigated solid tip RFA catheter. PMID- 26138177 TI - Role of angiotensin II type I (AT1 A1166C) receptor polymorphism in susceptibility of left ventricular dysfunction. AB - BACKGROUND: Left ventricular dysfunction (LVD) with subsequent congestive heart failure (CHF) constitutes the final common pathway for a host of cardiac disorders. The impaired LV function develops in response to an ischemic insult followed by a fall in cardiac output that leads to activation of renin angiotensin-system (RAS). Angiotensin II type I receptor (AT1), which mediate the vasoconstrictive and salt-conserving actions of the RAS, represent interesting candidate genes for cardiovascular diseases. Therefore, we conducted an association study between single nucleotide polymorphism (SNP) in AT1 gene and LVD in CAD patients. METHODS AND RESULTS: The present study recruited a total of 950 subjects including 720 angiography confirmed CAD patients and 230 healthy controls. Among 720 CAD patients, 229 with reduced left ventricle ejection fraction (LVEF<=45%) were categorized as LVD. The AT1 (A1166C, rs5186) polymorphism was determined by ARMS-PCR. Our results showed that the frequency of AT1 1166AC and CC genotypes were significantly higher in LVD patients in comparison to non-LVD (LVEF >45%) patients (p value = 0.003; OR = 1.81 and p value <0.001; OR = 4.33). Further analysis showed that AT1 A1166C polymorphism was significantly associated with LV end diastole (p-value = 0.031), end systole (p-value = 0.038) dimensions, and mean LVEF (p-value = 0.035). Moreover, on comparing the AT1 A1166C polymorphism in CAD patients with healthy controls, we did not find any association both at genotypic and allelic level (p value = 0.927; OR = 1.04 and p value = 0.219; OR = 0.83) respectively. CONCLUSIONS: Our study suggests that AT1 A1166C polymorphism may play significant role in conferring genetic susceptibility of LVD. PMID- 26138178 TI - fQRS as a marker of granulomatous disease in patients presenting with ventricular tachycardia and normal left ventricular ejection fraction. AB - BACKGROUND: Granulomatous myocarditis may present with sustained monomorphic ventricular tachycardia (SMVT) in the presence of normal left ventricular ejection fraction (LVEF), and could be mistaken for idiopathic ventricular tachycardia (IVT). The use of cardiac imaging for diagnosis can be limited by availability and high cost. ECG is readily available and inexpensive. Fragmented QRS (fQRS) on ECG has been found to be associated with myocardial scar. We hypothesized that fQRS could be useful in the diagnosis of granulomatous VT (GVT). METHODS: We compared the 12-lead ECG of 16 patients with GVT and 42 patients with IVT who presented with SMVT. RESULTS: The presence of fQRS was significantly higher in the GVT group compared to the IVT group (75% versus 19.1%, p < 0.001). The location of fQRS correlated with delayed enhancement cardiac magnetic resonance imaging (DE-CMR) in the same segment in 4/16 patients in the GVT group. It correlated with an affected segment on either DE-CMR or 18FDG positron emission computed tomography in 4/11 patients in the GVT group who had both imaging modality. Whenever fQRS was present in contiguous leads other than the inferior leads, it always corresponded to an affected segment on imaging. CONCLUSIONS: In patients presenting with SMVT and no structural heart disease, the presence of fQRS is strongly associated with granulomatous myocarditis. fQRS on the surface ECG is a helpful tool the presence of which should prompt a CMR for a definitive diagnosis. PMID- 26138179 TI - Elevated oxidative stress among coronary artery disease patients on statin therapy: A cross sectional study. AB - BACKGROUND: Statins are a major group of drugs that reduces LDL-C levels, which are proven to have other beneficial effects such as preventing coronary events. The objective of this study was to evaluate oxidative stress and select novel coronary artery disease risk factors among coronary artery disease patients on statins. METHODS: In this observational, cross-sectional study, we compared total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein B, lipoprotein (a), homocysteine, reduced glutathione, glutathione peroxidase, superoxide dismutase, ascorbic acid, malondialdehyde and oxidized LDL among male coronary artery disease patients on statin therapy (group 2, n = 151) with sex matched, diabetic patients (group 3, n = 80) as well as healthy controls (group 1, n = 84). RESULTS: Total cholesterol, triglycerides, HDL-cholesterol and LDL cholesterol were significantly lower among subjects of group 2 compared to other two groups. The novel risk factors studied did not differ significantly between groups, except for a higher homocysteine level among group 2 subjects compared to the other two groups. Elevated oxidative stress, indicated by lower reduced glutathione, glutathione peroxidase, and ascorbic acid as well as higher malondialdehyde and oxidized LDL was observed among group 2 subjects. Triglycerides, HDL-cholesterol, ascorbic acid and malondialdehyde were found to be independent predictors for coronary artery disease among this study population. CONCLUSIONS: Though coronary artery disease subjects had healthy lipid profile, oxidative stress, a recognized risk factor for coronary events, was still elevated among this patient group. Novel risk factors were not found to be major predictors for coronary artery disease among the study subjects. PMID- 26138180 TI - Prospective study to evaluate safety and efficacy of Zotarolimus Eluting Stent (PSEZES) in patients with long coronary artery lesions. AB - BACKGROUND: Although the safety and effectiveness of Drug-Eluting Stents (DES) has been established extensively, reports on long term clinical outcome with angiographic findings in patients with long coronary artery lesions are not many. METHODS: In this single-center prospective registry of 100 patients, a total of 110 denovo long lesions (>20 mm) were treated with Resolute Zotarolimus Eluting Stent (R-ZES). The patients were followed up clinically at 3, 6 and 12 months and follow up coronary angiography was performed at 9-months. The primary end point was one year rate of target lesion failure (TLF) which is a composite of cardiac death, target lesion myocardial infarction or ischemia driven target lesion revascularization (TLR). The secondary end points included definite or probable stent thrombosis, 9-month angiographic restenosis and late lumen loss. RESULTS: The mean age of patients was 58.7 +/- 9.50 years with prevalence of diabetes as high as 60%. The mean lesion length was 24.67 +/- 4.87 mm with a mean reference vessel diameter of 2.85 +/- 0.32 mm and 67.3% were Type C lesions (ACC/AHA classification). Two patients died during follow-up, of which one was non-cardiac death. One patient had target vessel myocardial infarction and five patients (4.5%) had ischemia driven TLR. The incidence of TLF was 6.36%. Binary restenosis was seen in 7 out of 93 lesions (7.5%). Median late lumen loss at 9 month was 0.22 mm. No stent thrombosis was noted in the study. CONCLUSION: Implantation of R-ZES in real-world patients with long coronary artery lesions is safe with comparable efficacy to what is observed in the treatment of less complex lesions. PMID- 26138181 TI - Does aortic valve sclerosis predicts the severity and complexity of coronary artery disease? AB - AIM: We assessed the association of aortic valve sclerosis (AVS) with atherosclerotic risk factors and severity and complexity of coronary artery disease (CAD). METHODS: In this retrospective study, a total of 482 eligible patients were divided into 2 groups: AVS present and AVS absent. All major cardiovascular risk factors and coronary lesion characteristics were included. RESULTS: Age was the only independent predictor of AVS. AVS was not independently associated with the number of obstructive vessels, degree of lesion obstruction and SYNTAX score. CONCLUSION: AVS is probably a benign marker of age-related degenerative changes in the heart independent of the severity and complexity of CAD. PMID- 26138182 TI - Prognostic significance of coronary sinus filling time in patients with angina and normal coronaries at one year follow up. AB - BACKGROUND: Coronary sinus filling time (CSFT) has been proposed as a simple method for assessment of coronary microvascular function in patients with angina and normal coronaries. But its correlation with inducible ischemia and prognostic significance in predicting future cardiovascular events has not been studied. The present study assessed the prognostic significance of CSFT during one year of follow up. METHODS: We compared coronary sinus filling time of patients with angina and normal coronaries with that of control population. Control group was formed by those patients with supraventricular arrhythmia undergoing radiofrequency ablation and having normal coronaries. Baseline treadmill test (TMT) parameters like workload, duration and Duke Score were assessed. Patients were followed up for one year and a composite of cardiovascular mortality and non fatal myocardial infarction was analyzed. Number of patients presenting to emergency or outpatient department with recurrent chest pain symptoms during one year follow up was considered for secondary outcome analysis. Coronary sinus filling time was analyzed with respect to cardiovascular events, repeat hospitalization for recurrent angina and TMT parameters. RESULTS: Total 72 patients and 16 controls were studied. Mean CSFT value in the study group was 5.31 +/- 1.03 sec and in the control group was 4.16 +/- 0.72 sec and the difference was significant (p value = 0.0001). No correlation was found between baseline and repeat TMT parameters with CSFT. There was no cardiovascular mortality or hospitalization for non-fatal MI during one year follow up. But patients with frequent emergency or outpatient department visits with chest pain had a high CSFT compared with asymptomatic patients (p value = 0.005). CONCLUSION: Coronary sinus filling time may be used as a simple marker of microvascular dysfunction in patients with angina and normal coronaries. Patients with recurrent chest pain symptoms after one year follow up were found to have high CSFT compared to asymptomatic patients. PMID- 26138183 TI - Making sense of health care delivery Where does the close to community health care worker fit in? - The case for congestive heart failure. AB - Close to community health care workers (CTC-HCW) is an increasingly used term to describe the emergence of a new partner in health services delivery. In strengthening arguments for this part of the health workforce the authorities, health staffers, supporters, sceptics and perhaps clients will look to the academicians and the evidence base to determine the fate of this group. There is no doubt, CTC-HCW are a vital resource, whose importance is tied to socio-demo geographic variables. Regardless of what the common perceptions of its importance are, the evolving evidence base could suggest either way. In this short commentary we would like to highlight the importance of a balanced and common sense approach in these arguments. An important example is heart failure where the majority have an associated comorbidity and one in four would also suffer with cognitive or mood disturbances. It is unclear how the CTC-HCW would fare for this devastating syndrome. In moving forward it is important we understand there are: strengths and limitations in the evidence gathering processes; indecision as to the questions; uncertainty of the starting points to gather evidence; and sociodemogeographic biases, which have to be factored before determining the fate of this much needed health care resource. PMID- 26138184 TI - Left main reconstruction as an alternative method to CABG after primary PCI complication. AB - Left main coronary artery disease is rare, accounting for 1% of all coronary artery disease and traditionally, is treated by coronary artery bypass grafting. We report our experience and five years follow up, after a coronary osteal surgical plasty in a young man who referred to our center with an anterior myocardial infarction. PMID- 26138185 TI - Total arterial anaortic off-pump coronary artery bypass grafting for diffuse coronary disease - A case report. AB - Surgical treatment of diffuse coronary artery disease remains challenging. We present here a diabetic patient, with diffuse coronary disease, revascularized using total arterial anaortic off-pump coronary artery bypass grafting. He received total nine distal grafts. He continues to be asymptomatic after more than 2 years. CT angiography follow-up shows eight out of nine grafts are patent. Anaortic off-pump coronary artery bypass grafting has the least incidence of stroke and arterial grafts have the best long-term patency rate. This is the first case report of nine arterial bypass graft performed off-pump using both internal mammary and both radial arteries. Anaortic total arterial off-pump coronary artery bypass grafting has achieved excellent intermediate term result in this patient of diffuse coronary artery disease. PMID- 26138186 TI - Aortic root abscess presenting as alternating bundle branch block: Infective endocarditis of bicuspid aortic valve. AB - Bicuspid aortic valve is the most common congenital cardiac malformation, affecting 1%-2% of the population. Among various complications, incidence of infective endocarditis (IE) in the bicuspid aortic valve population is high with higher rate of periannular extension resulting in conduction disturbances. Here we are reporting a rare case of infective endocarditis of bicuspid aortic valve presented with alternating bundle branch block. PMID- 26138187 TI - Managing distorted ABSORB Scaffold in left main during anomalous LMCA stenting. AB - The everolimus-eluting biovascular scaffold (BVS) does not contain any metal, therefore struts are not evident angiographically. Two adjacent platinum radio opaque markers at each end facilitate precise location of stent ends. Here we report one case of anomalous left main stenting using BVS. The BVS got accidentally distorted in left main during the procedure, which was not visible on angiography but detected on OCT. PMID- 26138188 TI - A large left ventricular pseudo-aneurysm. PMID- 26138189 TI - Quadricuspid pulmonary valve associated with atrial septal defects and pulmonary stenosis. AB - A 1-month-old Hispanic female was referred to the cardiology service. During physical examination, a systolic ejection murmur at the pulmonic area was auscultated. The echocardiography evaluation of the pulmonary valve demonstrated a quadricuspid pulmonary valve (QPV) with slightly thickened leaflets, associated atrial septal defects and mild pulmonary stenosis. QPV is a rare congenital anomaly variant that can remain asymptomatic with few or non-hemodynamic alterations. Associations with structural or functional alterations have been reported. This is the first case of QPV that was diagnosed in a Hispanic newborn. PMID- 26138190 TI - How to tackle complications in radial procedures: Tip and tricks. AB - Transradial interventions (TRI) are becoming increasingly popular because of accumulating recent evidence suggesting improved survival and reduced morbidity. Complications, though rare, do occur, especially for operators on their learning curve. The complications are best prevented by utilization of proper technique. Forearm hematoma are preventable and easy to treat, but a delay in detecting and managing them can lead to disastrous consequences compartment syndrome being the most dreaded one. This review deals with tips and tricks to prevent as also treat the common and rare complications. PMID- 26138192 TI - Cardiac aspergilloma. PMID- 26138191 TI - ICAM-1 molecular mechanism and genome wide SNP's association studies. AB - Macrophages transformed foam cell formation occurs as a result of leukocyte accumulation mediated through intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and E-selectin, secreted by inflamed or damaged endothelium. The key molecule is the ICAM-1, member of the adhesion immunoglobulin super family that maps to chromosome 19 p13.2-p13.3 codes for 505 amino acids have five extracellular domains including circulatory leukocytes binding site (primarily monocytes) for recruiting it at the sites of inflammation and the tight adhesion with vascular endothelium for the above mentioned pathogenesis as an initial step. Hence the objective of the current paper is to review the Genome Wide Association (GWA) studies and summarizes its understanding of functional Single Nucleotide Polymorphism (SNP's) of ICAM-1 clinical association to provide better guidance for the clinicians and researchers of the merits, demerits of the current results and direct them to do research on larger number of population for better prospective. PMID- 26138193 TI - Synthesis of new fluorinated analogs of GABA, Pregabalin bioisosteres, and their effects on [(3)H]GABA uptake by rat brain nerve terminals. AB - Fluorinated analogs of natural substances take an essential place in the design of new biologically active compounds. New fluorinated analogs of gamma aminobutyric acid, that is, beta-polyfluoroalkyl-GABAs (FGABAs), were synthesized with substituents: beta-CF3-beta-OH (1), beta-CF3 (2); beta-CF2CF2H (3). FGABAs are bioisosteres of Pregabalin (Lyrica(r), Pfizer's blockbuster drug, beta-i-Bu GABA), and have lipophilicity close to this medicine. The effects of synthesized FGABAs on [(3)H]GABA uptake by isolated rat brain nerve terminals (synaptosomes) were assessed and compared with those of Pregabalin. FGABAs 1-3 (100MUM) did not influence the initial velocity of [(3)H]GABA uptake when applied acutely, whereas an increase in this parameter was found after preliminary incubation of FGABAs with synaptosomes. Pregabalin after preliminary incubation with synaptosomes caused unidirectional changes in the initial velocity of [(3)H]GABA uptake. Using specific inhibitors of GAT1 and GAT3, NO-711 and SNAP5114, respectively, the ability of FGABAs 1-3 to influence non-GAT1 and non-GAT3 uptake activity of nerve terminals was analyzed, but no specificity was found. Therefore, new synthesized FGABAs are structural but not functional analogs of GABA (because they did not inhibit synaptosomal [(3)H]GABA uptake). Moreover, FGABAs are able to increase the initial velocity of [(3)H]GABA uptake by synaptosomes, and this effect is higher than that of Pregabalin. PMID- 26138194 TI - Intriguing possibilities and beneficial aspects of transporter-conscious drug design. AB - It has been revealed that many types of drugs interact with transporter proteins within an organism. Transporter proteins absorb or excrete materials, including drugs and nutrients, across the cell membrane. Some hydrophobic drugs are excreted from the cell as xenobiotics by ATP-binding cassette (ABC) transporters. However, solute carrier (SLC) transporters are tissue-specifically expressed and have substrate specificities. Thus, transporter-conscious drug design is an excellent method of delivering drugs to pharmaceutical target organs and provides advantages in absorption, distribution, excretion, and toxicity of drugs (ADMET) due to transport systems. In fact, based on this strategy, the bioavailability of prodrugs designed as peptide transporter 1 (PEPT1) substrates was better than that of the corresponding parent compounds due to the transport system in the small intestine. Furthermore, in central nervous system (CNS) drug developing, drug delivery into brain across the blood-brain barrier (BBB) is a serious problem. However, this problem can be also solved by the use of the transport systems at the BBB. Therefore, transporter-consciously designed drugs not only may effectively elicit activity but also may control adverse side effects caused by off-targets and drug-drug interactions and, consequently, may show good performance in clinical trials. In this review, I introduce possibilities and advantages of transporter-conscious drug designs. PMID- 26138202 TI - Gene "switch" stops colon cancer in mice. AB - Researchers developed a mouse model that enabled them to alternately silence and reactivate the tumor suppressor gene adenomatous polyposis coli, which is mutated in the majority of human colorectal cancers. When the tumor suppressor gene was reactivated, the tumors completely regressed within 2 weeks, even in the presence of mutations that commonly sustain disease progression. PMID- 26138195 TI - Synthesis and biological characterization of a promising F-18 PET tracer for vesicular acetylcholine transporter. AB - Nine fluorine-containing vesicular acetylcholine transporter (VAChT) inhibitors were synthesized and screened as potential PET tracers for imaging the VAChT. Compound 18a was one of the most promising carbonyl-containing benzovesamicol analogs; the minus enantiomer, (-)-18a displayed high potency (VAChT Ki=0.59 +/- 0.06 nM) and high selectivity for VAChT versus sigma receptors (>10,000-fold). The radiosynthesis of (-)-[(18)F]18a was accomplished by a two-step procedure with 30-40% radiochemical yield. Preliminary biodistribution studies of (-) [(18)F]18a in adult male Sprague-Dawley rats at 5, 30, 60 and 120 min post injection (p.i.) were promising. The total brain uptake of (-)-[(18)F]18a was 0.684%ID/g at 5 min p.i. and by 120 min p.i. slowly washed out to 0.409 %ID/g; evaluation of regional brain uptake showed stable levels of ~0.800 %ID/g from 5 to 120 min p.i in the VAChT-enriched striatal tissue of rats, indicating the tracer had crossed the blood brain barrier and was retained in the striatum. Subsequent microPET brain imaging studies of (-)-[(18)F]18a in nonhuman primates (NHPs) showed high striatal accumulation in the NHP brain; the standardized uptake value (SUV) for striatum reached a maximum value of 5.1 at 15 min p.i. The time-activity curve for the target striatal region displayed a slow and gradual decreasing trend 15 min after injection, while clearance of the radioactivity from the cerebellar reference region was much more rapid. Pretreatment of NHPs with 0.25mg/kg of the VAChT inhibitor (-)-vesamicol resulted in a ~90% decrease of striatal uptake compared to baseline studies. HPLC metabolite analysis of NHP plasma revealed that (-)-[(18)F]18a had a good in vivo stability. Together, these preliminary results suggest (-)-[(18)F]18a is a promising PET tracer candidate for imaging VAChT in the brain of living subjects. PMID- 26138196 TI - The calcium-activated potassium channel KCa3.1 plays a central role in the chemotactic response of mammalian neutrophils. AB - AIM: Neutrophils are the first cells to arrive at sites of injury. Nevertheless, many inflammatory diseases are characterized by an uncontrolled infiltration and action of these cells. Cell migration depends on volume changes that are governed by ion channel activity, but potassium channels in neutrophil have not been clearly identified. We aim to test whether KCa3.1 participates in neutrophil migration and other relevant functions of the cell. METHODS: Cytometer and confocal measurements to determine changes in cell volume were used. Cells isolated from human, mouse and horse were tested for KCa3.1-dependent chemotaxis. Chemokinetics, calcium handling and release of reactive oxygen species were measured to determine the role of KCa3.1 in those processes. A mouse model was used to test for neutrophil recruitment after acute lung injury in vivo. RESULTS: We show for the first time that KCa3.1 is expressed in mammalian neutrophils. When the channel is inhibited by a pharmacological blocker or by genetic silencing, it profoundly affects cell volume regulation, and chemotactic and chemokinetic properties of the cells. We also demonstrated that pharmacological inhibition of KCa3.1 did not affect calcium entry or reactive oxygen species production in neutrophils. Using a mouse model of acute lung injury, we observed that Kca3.1(-/-) mice are significantly less effective at recruiting neutrophils into the site of inflammation. CONCLUSIONS: These results demonstrate that KCa3.1 channels are key actors in the migration capacity of neutrophils, and its inhibition did not affect other relevant cellular functions. PMID- 26138203 TI - Brief report: intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: location-independent post hoc analysis using magnetic resonance imaging. AB - OBJECTIVE: To determine whether an anabolic drug (sprifermin) is capable of reducing cartilage loss wherever it occurs in a given knee, using a subject specific, location-independent analysis of cartilage change in patients with knee osteoarthritis (OA). METHODS: Study participants (n = 168; ages >=40 years, 69% women) had symptomatic femorotibial OA not confined to the medial compartment. Sprifermin (10, 30, or 100 MUg) or placebo was injected intraarticularly 3 times over 3 weeks, both after randomization (baseline) and 3 months later. Coronal magnetic resonance images were acquired at baseline and 3, 6, and 12 months after treatment. The femorotibial cartilage of each subject was segmented, and changes in cartilage thickness were computed across 16 subregions. Location-independent post hoc analysis was used to compute summary scores of negative and positive changes in the subregions, summarized as the total cartilage thinning sum score (ThCTnS) and the total cartilage thickening sum score (ThCTkS), capturing change in either direction in each knee. Ordered values of the magnitude of subject specific subregional changes in thickness were determined. The ThCTnS and ThCTkS in each sprifermin dose group at 12 months of followup were compared with the values in the matched placebo groups, using the Wilcoxon-Mann-Whitney test. RESULTS: The mean +/- SD ThCTnS was -591 +/- 617 MUm (median -360 MUm, Q1/Q3 = 820/-200 MUm) in patients treated with 100 MUg sprifermin (n = 57), and -921 +/- 777 MUm (median -745 MUm, Q1/Q3 = -1,190/-380 MUm) in patients given placebo (n = 18). The mean difference in the ThCTnS between the 100-MUg sprifermin group and the placebo group was 331 MUm (95% confidence interval [95% CI] 24, 685), a difference that was statistically significant (P = 0.03). The mean difference in the ThCTkS in the 100-MUg sprifermin group compared with the placebo group was 237 MUm (95% CI 34, 440), also a statistically significant difference (P = 0.028). CONCLUSION: Sprifermin not only increases cartilage thickness, but also reduces cartilage loss. Subject-specific, location-independent analysis of both cartilage thinning and thickening represents a sensitive and informative approach for studying the effects of disease-modifying OA drugs. PMID- 26138204 TI - Outcomes After Cardioversion in Atrial Fibrillation Patients Treated with Non Vitamin K Antagonist Oral Anticoagulants (NOACs): Insights from a Meta-Analysis. AB - BACKGROUND: There are limited data on outcomes following cardioversion in atrial fibrillation (AF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). A meta-analysis was performed to evaluate the efficacy and safety of NOACs in patients with AF undergoing cardioversion. METHODS: PubMed, Cochrane Library, EMBASE, Web of Science and CINAHL databases were searched from January 1, 2001 through to October 30, 2014. Randomized controlled trials (RCTs) comparing NOACs (apixaban, rivaroxaban and dabigatran) with warfarin in AF patients undergoing cardioversion were selected. The primary efficacy outcome was stroke and systemic embolism, and the primary safety outcome was major or clinically relevant non-major (CRNM) bleeding. We used random effects models. RESULTS: Four RCTs were included, involving a total of 3635 randomized participants who underwent a total of 4257 cardioversions. A total of 12 events of stroke and systemic embolism were found in the NOAC group and ten events in the warfarin group [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.31-1.72]. Risk of major or CRNM bleeding was not different with NOACs, when compared with warfarin (OR 1.41, 95% CI 0.87-2.28). CONCLUSIONS: Data from patients enrolled in RCTs, showed that NOACs are effective and safe for AF patients undergoing cardioversion. PMID- 26138205 TI - Associations between hoof shape and the position of the frontal plane ground reaction force vector in walking horses. AB - AIMS: To determine the frontal plane position of the ground reaction force vector at its centre of pressure under the hoof of walking horses, and its projection through the distal limb joints, and to relate this to hoof geometric measurements. METHODS: Reflective markers were glued to the forelimb hooves and skin of 26 horses, over palpable landmarks representing centres of the coffin, fetlock and carpal joints, and the dorsal toe at its most distal point. A 4 camera kinematic system recorded the position of these markers as the horse walked in hand across a force platform, to generate a frontal plane representation of the ground reaction force vector passing between the markers at the joints. The position of the vector was calculated as the relative distance between the lateral (0%) and medial (100%) markers at each joint. Digital photos were taken of the hoof in frontal and sagittal views to determine hoof geometric measurements. Associations between these and the position of the force vector at each joint were examined using Pearson correlation coefficients. RESULTS: Mean vector position for both forelimbs at the toe, coffin, fetlock and carpal joint was 50.1 (SD 8.9), 53.0 (SD 9.2), 54.6 (SD 11.4) and 50.5 (SD17.3)%, respectively, of the distance between the lateral and medial sides of the joint in the frontal plane. Across all four joints, the vector position was slightly more medial (2-4%) for the right than left limb (p>0.05). Medial hoof wall angle was correlated (p<0.05) with force vector position at the fetlock (r=-0.402) and carpal (r=-0.317) joints; lateral hoof wall angle with vector position at the toe (r=0.288) and carpal (r=-0.34) joint, and medial hoof wall height with vector position at the fetlock (r=-0.306) and carpal (r=-0.303) joints. CONCLUSION: The position of the two-dimensional frontal plane ground reaction force vector at the toe, and at the fetlock and carpal joints was associated with hoof shape. Mediolateral hoof balance has been shown in vitro to affect articular forces, which may be a factor in development of joint disease. The effect of hoof shape needs to be evaluated at faster gaits to determine the potential for joint injury in the presence of larger forces. PMID- 26138206 TI - Conformational Entropy of Intrinsically Disordered Proteins from Amino Acid Triads. AB - This work quantitatively characterizes intrinsic disorder in proteins in terms of sequence composition and backbone conformational entropy. Analysis of the normalized relative composition of the amino acid triads highlights a distinct boundary between globular and disordered proteins. The conformational entropy is calculated from the dihedral angles of the middle amino acid in the amino acid triad for the conformational ensemble of the globular, partially and completely disordered proteins relative to the non-redundant database. Both Monte Carlo (MC) and Molecular Dynamics (MD) simulations are used to characterize the conformational ensemble of the representative proteins of each group. The results show that the globular proteins span approximately half of the allowed conformational states in the Ramachandran space, while the amino acid triads in disordered proteins sample the entire range of the allowed dihedral angle space following Flory's isolated-pair hypothesis. Therefore, only the sequence information in terms of the relative amino acid triad composition may be sufficient to predict protein disorder and the backbone conformational entropy, even in the absence of well-defined structure. The predicted entropies are found to agree with those calculated using mutual information expansion and the histogram method. PMID- 26138207 TI - Effect of Clothing on Measurement of Bone Mineral Density. AB - It is unknown whether allowing patients to have BMD (bone mineral density) studies acquired while wearing radiolucent clothing adlib contributes appreciably to the measurement error seen. To examine this question, a spine phantom was scanned 30 times without any clothing, while draped with a gown, and while draped with heavy winter clothing. The effect on mean BMD and on SD (standard deviation) was assessed. The effect of clothing on mean or SD of the area was not significant. The effect of clothing on mean and SD for BMD was small but significant and was around 1.6% for the mean. However, the effect on BMD precision was much more clinically important. Without clothing the spine phantom had an least significant change of 0.0077 gm/cm(2), while when introducing variability of clothing the least significant change rose as high as 0.0305 gm/cm(2). We conclude that, adding clothing to the spine phantom had a small but statistically significant effect on the mean BMD and on variance of the measurement. It is unlikely that the effect on mean BMD has any clinical significance, but the effect on the reproducibility (precision) of the result is likely clinically significant. PMID- 26138208 TI - Effect of patient position on measurement of patellar height ratio. AB - BACKGROUND: Patient position is an important factor which can affect the accuracy of patellar height ratio measurement. Varying degree of knee flexion angles and action of quadriceps muscle while supine or standing positions are the most concerning factors. METHODS: Forty healthy subjects had radiographs taken of their knees at 0 degrees , 30 degrees , and 60 degrees of flexion in the supine (non-weight-bearing) and standing (weight-bearing) positions. Patellar height was assessed by five different measurement methods including Insall-Salvati (IS), Modified Insall-Salvati (MIS), Caton-Deschamps (CD), Blackburne-Peel (BP), and Knee triangular ratio (KT). RESULTS: The mean and standard deviation (SD) in the supine/standing position of each method were IS 1.0 (0.1)/1.05 (0.1), MIS 1.6 (0.2)/1.8 (0.3), CD 1.0 (0.2)/1.2 (0.2), BP 0.9 (0.2)/1.0(0.2), and KT 1(0.1)/1(0.1). Significant differences were found between supine and standing positions using all of the methods except for KT ratio. Comparisons between the various knee flexion angles were found to be statistically significant by most of the measurement methods, although the differences between the means were less than their SD. CONCLUSION: Quadriceps action had a significant influence on the mean values obtained by the MIS, CD, and BP methods. In clinical practice, interpretation for patella alta or patella baja of these measurement methods should be normalized according to the patient position. Varying the degree of knee flexion did not produce clinically important effects in any of the five patellar height measurement methods. PMID- 26138209 TI - The volume of the human knee joint. AB - INTRODUCTION: Despite its clinical relevance, particularly in septic knee surgery, the volume of the human knee joint has not been established to date. Therefore, the objective of this study was to determine knee joint volume and whether or not it is dependent on sex or body height. METHODS: Sixty-one consecutive patients (joints) who were due to undergo endoprosthetic joint replacement were enrolled in this prospective study. During the operation, the joint volume was determined by injecting saline solution until a pressure of 200 mmHg was achieved in the joint. RESULTS: The average volume of all knee joints was 131 +/- 53 (40-290) ml. The volume was not found to be dependent on sex, but it was dependent on the patients' height (R = 0.312, p = 0.014). This enabled an estimation of the joint volume according to V = 1.6 height - 135. CONCLUSIONS: The considerable inter-individual variance of the knee joint volume would suggest that it should be determined or at least estimated according to body height if the joint volume has consequences for the diagnostics or therapy of knee disorders. PMID- 26138210 TI - Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts. AB - PURPOSE: Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na (+) current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazine modifies the electrophysiological responses induced by acute mechanical stretch. METHODS: The ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (n = 9) or during perfusion of the late Na(+) current blocker ranolazine 5 MUM (n = 9). Spectral and mapping techniques were used to establish the ventricular fibrillation dominant frequency, the spectral concentration and the complexity of myocardial activation in three situations: baseline, stretch and post-stretch. RESULTS: Ranolazine attenuated the increase in ventricular fibrillation dominant frequency produced by stretch (23.0 vs 40.4 %) (control: baseline =13.6 +/- 2.6 Hz, stretch = 19.1 +/- 3.1 Hz, p < 0.0001; ranolazine: baseline = 1.4 +/- 1.8 Hz, stretch =14.0 +/- 2.4 Hz, p < 0.05 vs baseline, p < 0.001 vs control). During stretch, ventricular fibrillation was less complex in the ranolazine than in the control series, as evaluated by the lesser percentage of complex maps and the greater spectral concentration of ventricular fibrillation. These changes were associated to an increase in the fifth percentile of VV intervals during ventricular fibrillation (50 +/- 8 vs 38 +/- 5 ms, p < .01) and in the wavelength of the activation (2.4 +/- 0.3 vs 1.9 +/- 0.2 cm, p < 0.001) under ranolazine. CONCLUSIONS: The late inward Na(+) current inhibitor ranolazine attenuates the electrophysiological effects responsible for the acceleration and increase in complexity of ventricular fibrillation produced by myocardial stretch. PMID- 26138211 TI - Centrifugo-pneumatic multi-liquid aliquoting - parallel aliquoting and combination of multiple liquids in centrifugal microfluidics. AB - The generation of mixtures with precisely metered volumes is essential for reproducible automation of laboratory workflows. Splitting a given liquid into well-defined metered sub-volumes, the so-called aliquoting, has been frequently demonstrated on centrifugal microfluidics. However, so far no solution exists for assays that require simultaneous aliquoting of multiple, different liquids and the subsequent pairwise combination of aliquots with full fluidic separation before combination. Here, we introduce the centrifugo-pneumatic multi-liquid aliquoting designed for parallel aliquoting and pairwise combination of multiple liquids. All pumping and aliquoting steps are based on a combination of centrifugal forces and pneumatic forces. The pneumatic forces are thereby provided intrinsically by centrifugal transport of the assay liquids into dead end chambers to compress the enclosed air. As an example, we demonstrate simultaneous aliquoting of 1.) a common assay reagent into twenty 5 MUl aliquots and 2.) five different sample liquids, each into four aliquots of 5 MUl. Subsequently, the reagent and sample aliquots are simultaneously transported and combined into twenty collection chambers. All coefficients of variation for metered volumes were between 0.4%-1.0% for intra-run variations and 0.5%-1.2% for inter-run variations. The aliquoting structure is compatible to common assay reagents with a wide range of liquid and material properties, demonstrated here for contact angles between 20 degrees and 60 degrees , densities between 789 and 1855 kg m(-3) and viscosities between 0.89 and 4.1 mPa s. The centrifugo pneumatic multi-liquid aliquoting is implemented as a passive fluidic structure into a single fluidic layer. Fabrication is compatible to scalable fabrication technologies such as injection molding or thermoforming and does not require any additional fabrication steps such as hydrophilic or hydrophobic coatings or integration of active valves. PMID- 26138212 TI - The Impact of Nonpolymerizable Swelling Agents On The Synthesis of Particles With Combined Geometric, Interfacial, and Compositional Anisotropy. AB - Seeded emulsion polymerization is by far the most successful synthetic method for making anisotropic particles with precise control and high throughput. However, this synthesis involves multiple steps and the types of anisotropic properties that have been made on particles are limited. Here, we demonstrate, by using two different types of nonpolymerizable swelling agents, that we can simplify this method while still producing colloidal dimers with combined anisotropic properties in geometry, interface, and composition. When we swell cross-linked polystyrene seed particles with a simple solvent toluene, without additional polymerization steps we can make dimers with asymmetric distribution of surface charges and roughness on two lobes by fast extraction of toluene. We further show that this toluene-swelling-extraction method can promote the surface modification of the second lobe selectively especially for hydrophilic and stimuli-responsive polymers, which was a significant challenge in dimer synthesis. When we change the swelling agent to a sol-gel precursor, that is, tetraethyl orthosilicate, we can make polystyrene-silica hybrid particles with different morphologies. Our method provides a facile synthetic platform for making colloidal particles with different types of anisotropic properties, which are expected to find important applications for colloidal surfactant, self-assembly, and artificial motors. PMID- 26138213 TI - Contrast Agent Mass Spectrometry Imaging Reveals Tumor Heterogeneity. AB - Mapping intratumoral heterogeneity such as vasculature and margins is important during intraoperative applications. Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated potential for intraoperative tumor imaging using validated MS profiles. The clinical translation of DESI-MS into a universal label-free imaging technique thus requires access to MS profiles characteristic to tumors and healthy tissues. Here, we developed contrast agent mass spectrometry imaging (CA-MSI) that utilizes a magnetic resonance imaging (MRI) contrast agent targeted to disease sites, as a label, to reveal tumor heterogeneity in the absence of known MS profiles. Human breast cancer tumors grown in mice were subjected to CA-MSI using Gadoteridol revealing tumor margins and vasculature from the localization of [Gadoteridol+K](+) and [Gadoteridol+Na](+) adducts, respectively. The localization of the [Gadoteridol+K](+) adduct as revealed through DESI-MS complements the in vivo MRI results. DESI-MS imaging is therefore possible for tumors for which no characteristic MS profiles are established. Further DESI-MS imaging of the flux of the contrast agent through mouse kidneys was performed indicating secretion of the intact label. PMID- 26138214 TI - Enrichment of bacteria samples by centrifugation improves the diagnosis of orthopaedics-related infections via real-time PCR amplification of the bacterial methicillin-resistance gene. AB - BACKGROUND: To effectively treat orthopaedic infections by methicillin-resistant strains, an early diagnosis is necessary. Bacterial cultures and real-time polymerase chain reaction (PCR) have been used to define methicillin-resistant staphylococci. However, even when patients display clinical signs of infections, bacterial culture and real-time PCR often cannot confirm infection. The aim of this study was to prospectively compare the utility of real-time PCR for the mecA gene detection following centrifugation of human samples with suspected orthopaedic infections. RESULTS: In addition to the conventional real-time PCR method, we performed real-time PCR following centrifugation of the sample at 4,830*g for 10 min in a modified real-time PCR (M-PCR) method. We suspended cultured methicillin-resistant Staphylococcus aureus and generated standard dilution series for in vitro experiments. The in vitro detection sensitivity of the M-PCR method was approximately 5.06 times higher than that of the conventional real-time PCR method. We performed bacterial culture, pathological examination, real-time PCR, and M-PCR to examine the infectious fluids and tissues obtained from 36 surgical patients at our hospital. Of these, 20 patients who had undergone primary total hip arthroplasty were enrolled as negative controls. In addition, 15 patients were examined who were clinically confirmed to have an infection, including periprosthetic joint infection (eight patients), pyogenic spondylitis (two patients), infectious pseudoarthrosis (two patients), and after spine surgery (three patients). In one sample from a patient who developed infectious pseudoarthrosis and two samples from surgical site infections after spine surgery, the mecA gene was detected only by the M-PCR method. In one patient with infectious pseudoarthrosis, one patient with infection after arthroplasty, and two patients with purulent spondylitis, the detection sensitivity of the M-PCR method was increased compared with PCR (clinical sample average: 411.6 times). CONCLUSIONS: These findings suggest that the M-PCR method is useful to detect methicillin-resistant strains infections. In addition, the centrifugation process only takes 10 min longer than conventional real-time PCR methods. We believe that the M-PCR method could be clinically useful to detect orthopaedic infections caused by methicillin-resistant strains. PMID- 26138215 TI - Firefighting to Innovation: Using Human Factors and Ergonomics to Tackle Slip, Trip, and Fall Risks in Hospitals. AB - OBJECTIVE: The aim of this study was to use a theoretical model (bench) for human factors and ergonomics (HFE) and a comparison with occupational slips, trips, and falls (STFs) risk management to discuss patient STF interventions (bedside). BACKGROUND: Risk factors for patient STFs have been identified and reported since the 1950s and are mostly unchanged in the 2010s. The prevailing clinical view has been that STF events indicate underlying frailty or illness, and so many of the interventions over the past 60 years have focused on assessing and treating physiological factors (dizziness, illness, vision/hearing, medicines) rather than designing interventions to reduce risk factors at the time of the STF. METHOD: Three case studies are used to discuss how HFE has been, or could be, applied to STF risk management as (a) a design-based (building) approach to embed safety into the built environment, (b) a staff- (and organization-) based approach, and (c) a patient behavior-based approach to explore and understand patient perspectives of STF events. RESULTS AND CONCLUSION: The results from the case studies suggest taking a similar HFE integration approach to other industries, that is, a sustainable design intervention for the person who experiences the STF event-the patient. APPLICATION: This paper offers a proactive problem-solving approach to reduce STFs by patients in acute hospitals. Authors of the three case studies use HFE principles (bench/book) to understand the complex systems for facility and equipment design and include the perspective of all stakeholders (bedside). PMID- 26138216 TI - Predictors of improvement in quality of life and pain relief in lumbar spinal stenosis relative to patient age: a study based on the Spine Tango registry. AB - BACKGROUND: An open decompression is the most common treatment for lumbar spinal canal stenosis (LSS), even in the elderly. However, it is not clear whether the treatment outcome is age dependent. The main purpose of this study was to evaluate the improvement in quality of life (QoL) and pain relief, after open decompression for LSS in relation to patient age. METHODS: The study was performed on the basis of Spine Tango registry data. The database query resulted in 4768 patients from 40 international Spine Tango centres. The patients were subdivided into three age groups: (1) 20-64, (2) 65-74, and (3) >=75 years. In multivariate logistic regression models, predictors for improvement in QoL and achievement of the minimum clinically relevant change in pain of two points were analysed. RESULTS: All groups benefited from significant improvement in QoL and back and leg pain relief. Age group had no significant influence on the outcomes. The preoperative status of each outcome was a predictor for its own postoperative outcome. Fewer previous surgeries, rigid or dynamic stabilization, and lower patient comorbidity also had a partially predictive influence for one or the other outcome. CONCLUSIONS: Our results confirm that all age groups significantly benefit from the open decompressive treatment of LSS. Age group had no significant influence on any outcome. PMID- 26138217 TI - Efficacy of ankle-brachial index as a preoperative screening in spine surgery. AB - PURPOSE: The aims of this study were to investigate the prevalence of peripheral arterial disease (PAD) and specify the patients who are necessary to measure ankle-brachial index (ABI) as a preoperative PAD screening in spine surgery. METHODS: A total of 1425 consecutive patients with non-emergency spine surgery underwent a PAD screening using ABI measurement. We reviewed their ABI data, age, smoking status, and co-morbidities including diabetes mellitus (DM), cerebrovascular disease (CVD) and ischemic heart disease (IHD). CT- or MR angiography was used for a definitive diagnosis of PAD when the ABI was 0.9 or less. RESULTS: Of 1425 patients, 37 patients (2.5%) showed less than 0.9 in ABI; 24 patients (1.6%) were eventually diagnosed as PAD. Of 24 patients with PAD, 22 patients (91.6%) were over 65 years. The prevalence of DM was 58.3% in the PAD group versus 18.7% in the non-PAD group (P < 0.05). Patients with CVD or IHD were more likely to have PAD, but the differences were not significant. Smoking rate was 62.5% in the PAD group versus 42.4% in the non-PAD group (P < 0.05). CONCLUSIONS: The current preoperative PAD screening data showed that age over 65 years, DM and smoking habit were the risk factors for PAD development. Based on the current results, we advocate preoperative ABI measurement for over 50-year patients who had co-morbidities and/or smoking habit and all the patients aged 65 years or more. PMID- 26138218 TI - Reply: To PMID 25900666. PMID- 26138219 TI - The Evolution and Functional Role of Flavin-based Prokaryotic Photoreceptors. AB - Flavin-based photoreceptor proteins of the LOV (light, oxygen and voltage) superfamily are ubiquitous and appear to be essential blue-light sensing systems not only in plants, algae and fungi, but also in prokaryotes, where they are represented in more than 10% of known species. Despite their broad occurrence, only in few cases LOV proteins have been correlated with important phenomena such as bacterial infectivity, selective growth patterns or/and stress responses; nevertheless these few known roles are helping us understand the multiple ways by which prokaryotes can exploit these soluble blue-light photoreceptors. Given the large number of sequences now deposited in databases, it becomes meaningful to define a signature for bona fide LOV domains, a procedure that facilitates identification of proteins with new properties and phylogenetic analysis. The latter clearly evidences that a class of LOV proteins from alpha-proteobacteria is the closest prokaryotic relative of eukaryotic LOV domains, whereas cyanobacterial sequences cluster with the archaeal and the other bacterial LOV domains. Distance trees built for LOV domains suggest complex evolutionary patterns, possibly involving multiple horizontal gene transfer events. Based on available data, the in vivo relevance and evolution of prokaryotic LOV is discussed. PMID- 26138220 TI - Low-frequency repetitive transcranial magnetic stimulation (rTMS), a new treatment option in neuropsychiatry. PMID- 26138221 TI - Establishing user needs for a stability assessment tool to guide wheelchair prescription. AB - PURPOSE: The WheelSense project aims to develop a system for assessing the stability and performance of wheelchairs through a user-centred design process. This study sought to capture user needs and define the specification for the system. METHOD: A mixed methods approach was adopted. An online survey was completed by 98 participants working in wheelchair provision. The results were built upon through 10 semi-structured interviews and one focus group (n = 5) with professionals working in wheelchair provision in three NHS Trusts in the UK. RESULTS: The results provided a picture of the current UK practice in stability testing. Issues with the reliability and usefulness of the existing methods used to assess the stability and performance of wheelchairs were highlighted. Requirements for a new system were ascertained. These included improved accuracy of tipping angles, features to support record keeping, improved client/carer education support and ability to model or predict client-wheelchair system performance in different configurations. CONCLUSIONS: The paper concludes that there is a need for improved tools to determine the stability of the client wheelchair system and support the prescription process, to ensure client safety and optimum equipment performance. A list of requirements has been produced to guide the future development of WheelSense. Implications for Rehabilitation The results of this survey and interview-based study present a picture of wheelchair stability testing practices in the UK, and highlight the need for new, more informative methods for guiding wheelchair prescription. The requirements for the design of a new system, or further development of existing tools to support the stability testing and prescription of wheelchairs have been established. PMID- 26138222 TI - Important wheelchair skills for new manual wheelchair users: health care professional and wheelchair user perspectives. AB - PURPOSE: The purpose of this project was to identify wheelchair skills currently being taught to new manual wheelchair users, identify areas of importance for manual wheelchair skills' training during initial rehabilitation, identify similarities and differences between the perspectives of health care professionals and manual wheelchair users and use the ICF to organize themes related to rehabilitation and learning how to use a manual wheelchair. METHOD: Focus groups were conducted with health care professionals and experienced manual wheelchair users. ICF codes were used to identify focus group themes. RESULTS: The Activities and Participation codes were more frequently used than Structure, Function and Environment codes. Wheelchair skills identified as important for new manual wheelchair users included propulsion techniques, transfers in an out of the wheelchair, providing maintenance to the wheelchair and navigating barriers such as curbs, ramps and rough terrain. Health care professionals and manual wheelchair users identified the need to incorporate the environment (home and community) into the wheelchair training program. CONCLUSIONS: Identifying essential components for training the proper propulsion mechanics and wheelchair skills in new manual wheelchair users is an important step in preventing future health and participation restrictions. Implications for Rehabilitation Wheelchair skills are being addressed frequently during rehabilitation at the activity dependent level. Propulsion techniques, transfers in an out of the wheelchair, providing maintenance to the wheelchair and navigating barriers such as curbs, ramps and rough terrain are important skills to address during wheelchair training. Environment factors (in the home and community) are important to incorporate into wheelchair training to maximize safe and multiple-environmental setting uses of manual wheelchairs. The ICF has application to understanding manual wheelchair rehabilitation for wheelchair users and therapists for improving the understanding of manual wheelchair use. PMID- 26138223 TI - Pharmacokinetics and pharmacodynamics of 3,3'-diindolylmethane (DIM) in regulating gene expression of phase II drug metabolizing enzymes. AB - 3,3'-Diindolylmethane (DIM) has been investigated as a potential anti-cancer chemopreventive agent in many preclinical and clinical studies. In this study, we sought to characterize the pharmacokinetics of DIM and to build a pharmacokinetic (PK) and pharmacodynamic (PD) model of the DIM-induced gene expression of phase II drug metabolizing enzymes (DME), which potentially links DIM's molecular effects to its in vivo chemopreventive efficacy. DIM (10 mg/kg) was administered intravenously (i.v.) to male Sprague-Dawley rats and blood samples were collected at selected time points for 48 h. The plasma concentration of DIM was determined using a validated HPLC method. The mRNA expression of NQO1, GSTP1 and UGT1A1 in blood lymphocytes was measured using quantitative PCR. An indirect response model was employed to relate the concentration of DIM to the expression of the genes NQO1, GSTP1 and UGT1A1, which were chosen as PD markers for DIM. After i.v. administration, the plasma concentration of DIM declined quickly, and the expression of target genes increased significantly, peaking at 1-2 h and then returning to basal levels after 24 h. The parameters in the PK-PD model were estimated. The PK-PD model aptly described the time delay and magnitude of gene expression induced by DIM. Our results indicate that DIM is effective at inducing various phase II DME, which are capable of detoxify carcinogens. This PK-PD modeling approach provides a framework for evaluating the acute effects of DIM or other similar drugs in clinical trials. PMID- 26138225 TI - Tedizolid Adsorption and Transmembrane Clearance during in vitro Continuous Renal Replacement Therapy. AB - BACKGROUND/AIMS: To study transmembrane clearance (CLTM) and adsorption of tedizolid, a novel oxazolidinone antibiotic, in continuous hemofiltration (CVVH) and continuous hemodialysis (CVVHD). METHODS: In vitro CVVH/CVVHD models with polysulfone and AN69 hemodiafilters were used. Tedizolid CLTM during CVVH/CVVHD was assessed at various ultrafiltrate (Quf) and dialysate rates (Qd). Tedizolid adsorption was tested in a recirculating CVVH model over 4 h. RESULTS: In CVVH, CLTM did not differ between filter types. In CVVHD, tedizolid CLTM was significantly higher with the polysulfone hemodiafilter at Qd 6 l/h (p < 0.02). Tedizolid exhibited irreversible adsorption to the CRRT apparatus and bound significantly higher to the polysulfone hemodiafilter. CONCLUSION: Tedizolid's CLTM is dependent on Qd, Quf, and hemodiafilter type. At conventional CRRT rates, tedizolid CLTM appears modest relative to total body clearance and is unlikely to require dose adjustments. CRRT adsorption in the clinical setting is likely less than what we observed in this in vitro, continuously recirculating blood model. PMID- 26138224 TI - In vivo bioimaging with tissue-specific transcription factor activated luciferase reporters. AB - The application of transcription factor activated luciferase reporter cassettes in vitro is widespread but potential for in vivo application has not yet been realized. Bioluminescence imaging enables non-invasive tracking of gene expression in transfected tissues of living rodents. However the mature immune response limits luciferase expression when delivered in adulthood. We present a novel approach of tissue-targeted delivery of transcription factor activated luciferase reporter lentiviruses to neonatal rodents as an alternative to the existing technology of generating germline transgenic light producing rodents. At this age, neonates acquire immune tolerance to the conditionally responsive luciferase reporter. This simple and transferrable procedure permits surrogate quantitation of transcription factor activity over the lifetime of the animal. We show principal efficacy by temporally quantifying NFkappaB activity in the brain, liver and lungs of somatotransgenic reporter mice subjected to lipopolysaccharide (LPS)-induced inflammation. This response is ablated in Tlr4(-/-) mice or when co administered with the anti-inflammatory glucocorticoid analogue dexamethasone. Furthermore, we show the malleability of this technology by quantifying NFkappaB mediated luciferase expression in outbred rats. Finally, we use somatotransgenic bioimaging to longitudinally quantify LPS- and ActivinA-induced upregulation of liver specific glucocorticoid receptor and Smad2/3 reporter constructs in somatotransgenic mice, respectively. PMID- 26138226 TI - Optimizing the clinical pharmacology of tuberculosis medications. AB - Tuberculosis (TB) treatment has changed little in the past 40 years. The current standard therapy requires four drugs for 2 months followed by two drugs for 4 months. This "short-course" regimen is not based on optimized pharmacokinetic and pharmacodynamic properties, but empiric evidence. A review of existing data suggests that pharmacokinetic variability with isoniazid and rifampin is greater than previously thought, and that efficacy is not as good as traditionally reported. Adding new drugs to the current regimen will be costly and time consuming. Maximizing the efficacy of the current medications is a less expensive and more feasible option. This article reviews the current potential of the first line TB drugs (rifamycins, isoniazid, pyrazinamide, and ethambutol) as well as the fluoroquinolones to introduce a true short-course TB regimen. PMID- 26138227 TI - Semiparametric transformation models for multiple continuous biomarkers in ROC analysis. AB - Recent technological advances continue to provide noninvasive and more accurate biomarkers for evaluating disease status. One standard tool for assessing the accuracy of diagnostic tests is the receiver operating characteristic (ROC) curve. Few statistical methods exist to accommodate multiple continuous-scale biomarkers in the framework of ROC analysis. In this paper, we propose a method to integrate continuous-scale biomarkers to optimize classification accuracy. Specifically, we develop semiparametric transformation models for multiple biomarkers. We assume that unknown and marker-specific transformations of biomarkers follow a multivariate normal distribution. Our models accommodate biomarkers subject to limits of detection and account for the dependence among biomarkers by including a subject-specific random effect. We also propose a diagnostic measure using an optimal linear combination of the transformed biomarkers. Our diagnostic rule does not depend on any monotone transformation of biomarkers and is not sensitive to extreme biomarker values. Nonparametric maximum likelihood estimation (NPMLE) is used for inference. We show that the parameter estimators are asymptotically normal and efficient. We illustrate our semiparametric approach using data from the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) study. PMID- 26138228 TI - Somatic-cell mutation induced by short exposures to cigarette smoke in urate null, oxidative stress-sensitive Drosophila. AB - We previously reported that a urate-null strain of Drosophila is hypersensitive to cigarette smoke (CS), and we suggested that CS induces oxidative stress in Drosophila because uric acid is a potent antioxidant. Although the carcinogenic risk of CS exposure is widely recognized; documentation of in vivo genotoxic activity of environmental CS, especially gaseous-phase CS, remains inconclusive. To date, somatic-cell mutations in Drosophila resulting from exposure to CS have not been detected via the somatic mutation and recombination test (wing spot test) with wild-type flies, a widely used Drosophila assay for the detection of somatic-cell mutation; moreover, genotoxicity has not been documented via a DNA repair test that involves DNA repair-deficient Drosophila. In this study, we used a new Drosophila strain (y v ma-l; mwh) to examine the mutagenicity induced by gaseous-phase CS; these flies are urate-null due to a mutation in ma-l, and they are heterozygous for multiple wing hair (mwh), a mutation that functions as a marker for somatic-cell mutation. In an assay with this newly developed strain, a superoxide anion-producing weed-killer, paraquat, exhibited significant mutagenicity; in contrast, paraquat was hardly mutagenic with a wild-type strain. Drosophila larvae were exposed to CS for 2, 4 or 6h, and then kept at 25 degrees C on instant medium until adulthood. After eclosion, mutant spots, which consisted of mutant hairs on wings, were scored. The number of mutant spots increased significantly in an exposure time-dependent manner in the urate-null females (ma-l (-/-)), but not in the urate-positive females (ma-l (+/-)). In this study, we showed that short-term exposure to CS was mutagenic in this in vivo system. In addition, we obtained suggestive data regarding reactive oxygen species production in larva after CS exposure using the fluorescence probe H2DCFDA. These results suggest that oxidative damage, which might be countered by uric acid, was partly responsible for induction of somatic cell mutations in Drosophila larvae exposed to CS. PMID- 26138229 TI - Continuous flow of nitroso Diels-Alder reaction. AB - Our flow reaction systems have provided quantitative yields of nitroso Diels Alder products with no byproducts in cases of cyclic dienes without temperature and pressure controls. Additionally, the reaction times were significantly shortened by using homogeneous catalyst (CuCl) or heterogeneous reagent (MnO2) in comparison with batch reaction. PMID- 26138230 TI - Introduction. PMID- 26138231 TI - Comparison of Pneumoperitoneum Volumes in Lift Laparoscopy With Variable Lift Locations and Tensile Forces. AB - OBJECTIVE: Evaluate the effect of peritoneal lift location and tensile force on peritoneal volume. STUDY DESIGN: Complete randomized block design. ANIMALS: Eleven fresh canine cadavers. METHODS: Cadavers underwent abdominal computed tomography (CT) scans after each treatment; 1) no lift, 2) umbilical lift with 15% body weight (BW) tension, 3) umbilical lift with 20% BW, 4) umbilical lift with 25% BW, 5) caudal lift with 15% BW, and 6) both umbilical and caudal lift with 15% BW shared equally between devices (dual lift). Isobaric pneumoperitoneal volume, instrument working distances, and transverse measures were calculated and normalized for each dog and compared across treatments. RESULTS: Increasing tensile force created a correspondingly larger pneumoperitoneal volume for the umbilical lift (0.34-0.40 total abdominal volume). Dual lifting created a larger pneumoperitoneal volume than either location alone at the same tension (0.39 total abdominal volume). Increasing lift tensions increased working distances, except to caudal abdominal structures. Increasing lift tensions at the umbilical location reduced the transverse diameter of the abdomen at the level of the kidney (0.92-0.86 total abdominal volume) and increased the transverse diameter at the midperitoneum (1.0-1.05 total abdominal volume). CONCLUSIONS: Larger isobaric penumoperitoneal volumes are produced with increased tensile force, or with dual lifting at lower force. A caudal lift leads to a small pneumoperitoneal volume but equivalent working space to caudal abdominal structures. Using an umbilical lift with moderate tensile force is preferable, providing good visualization and working space. Caudal lifting may be utilized to access caudal abdominal structures. PMID- 26138232 TI - Computed Tomography Determined Changes in Position of the Hepatobiliary and Gastrointestinal Systems after CO2 Insufflation to Determine Optimal Positioning for Abdominal Laparoscopy. AB - OBJECTIVE: To evaluate changes in body position and effect of CO2 insufflation on the hepatobiliary and gastrointestinal systems using computed tomography (CT) to determine optimal laparoscopic approach. STUDY DESIGN: Experimental study. ANIMALS: Healthy intact female Beagles (n = 6) of similar age, weight, and body condition score. METHODS: Urinalysis, peripheral blood smear, and abdominal ultrasonography were performed to determine dog health. A series of pre insufflation (PrI) CT scans in ventrodorsal routine (VDR), ventrodorsal Trendelenburg (VDT), left lateral (LL), and right lateral (RL) recumbency were performed before and after abdominal insufflation (PoI) with CO2 (10-14 mm Hg). Pre-determined measurements were made on PrI and PoI scans and differences compared. RESULTS: Liver position was affected by body position and under gravitational influence moved to the dependent part of the abdominal cavity. The gallbladder was best exposed in LL. Stomach position was not significantly changed after insufflation. Different areas of small intestine were dependent on gravitational effects. The pancreas maintained a similar position after insufflation. CONCLUSIONS: VDR was the ideal position for all laparoscopic procedures of the liver. The LL position could be used for surgery of the gallbladder but likely provides poor exposure to the rest of the liver. In approaching the stomach and intestines, the area of interest should be used to determine the best position. PMID- 26138233 TI - Mechanistic insight into conjugated N-N bond cleavage by Rh(III)-catalyzed redox neutral C-H activation of pyrazolones. AB - Density functional theory (DFT) calculations have been performed to investigate the detailed mechanism of Rh(III)-catalyzed redox-neutral C-H activation of pyrazolones with PhC=CPh. It is found that (1) the methylene C-H activation is prior to the phenyl C-H activation, (2) the N-N bond cleavage is realized via Rh(III) -> Rh(I) -> Rh(III) rather than via Rh(III) -> Rh(V) -> Rh(III). The zwitterionic Rh(I) complex is identified to be a key intermediate in promoting the N-N bond cleavage. (3) Different from the Rh(III)-catalyzed hydrazine directed C-H activation for indole synthesis, the rate-determining step of the reaction studied in this work is the Rh(III) -> Rh(I) -> Rh(III) process resulting in the N-N bond cleavage rather than the alkyne insertion step. The present theoretical study provides new insight into the mechanism of the conjugated N-N bond cleavage. PMID- 26138234 TI - Co-Inheritance of Functional Podocin Variants with Heterozygous Collagen IV Mutations Predisposes to Renal Failure. AB - BACKGROUND/AIMS: A subset of patients who present with proteinuria and are diagnosed with focal segmental glomerulosclerosis (FSGS) have inherited heterozygous COL4A3/A4 mutations and are also diagnosed with thin basement membrane nephropathy (TBMN-OMIM: 141200). Two studies showed that co-inheritance of NPHS2-p.Arg229Gln, a podocin variant, may increase the risk for proteinuria and renal function decline. METHODS: We hypothesized that additional podocin variants may exert a similar effect. We studied genetically a well-characterized Cypriot TBMN patient cohort by re-sequencing the NPHS2 coding region. We also performed functional studies in cell culture experiments, investigating the interaction of podocin variants with itself and with nephrin. RESULTS: Potentially disease-modifying podocin variants were searched for by analyzing NPHS2 in 35 'severe' TBMN patients. One non-synonymous variant, p.Glu237Gln, was detected. Both variants, p.Arg229Gln and p.Glu237Gln, were tested in a larger cohort of 122 TBMN patients, who were categorized as 'mild' or 'severe' based on the presence of microscopic hematuria alone or combined with chronic renal failure and/or proteinuria. Seven 'severe' patients carried either of the 2 variants; none was present in the 'mild' patients (p = 0.05, Pearson chi(2)). The 7 carriers belong in 2 families segregating mutation COL4A3-p.Gly1334Glu. Inheritance of the wild-type (WT) and mutant alleles correlated with the phenotype (combined concordance probability 0.003). Immunofluorescence (IF) experiments after dual co-transfection of WT and mutant podocin suggested altered co-localization of mutant homodimers. IF experiments after co-transfection of WT podocin and nephrin showed normal membrane localization, while both podocin variants interfered with normal trafficking, demonstrating perinuclear staining. Immunoprecipitation experiments showed stronger binding of mutant podocin to WT podocin or nephrin. CONCLUSION: The results support the hypothesis that certain hypomorphic podocin variants may act as adverse genetic modifiers when co inherited with COL4A3/A4 mutations, thus predisposing to FSGS and severe kidney function decline. PMID- 26138235 TI - Structural brain aberrations associated with the dissociative subtype of post traumatic stress disorder. AB - OBJECTIVE: One factor potentially contributing to the heterogeneity of previous results on structural grey matter alterations in adult participants suffering from post-traumatic stress disorder (PTSD) is the varying levels of dissociative symptomatology. The aim of this study was therefore to test whether the recently defined dissociative subtype of PTSD characterized by symptoms of depersonalization and derealization is characterized by specific differences in volumetric brain morphology. METHOD: Whole-brain MRI data were acquired for 59 patients with PTSD. Voxel-based morphometry was carried out to test for group differences between patients classified as belonging (n = 15) vs. not belonging (n = 44) to the dissociative subtype of PTSD. The correlation between dissociation (depersonalization/derealization) severity and grey matter volume was computed. RESULTS: Patients with PTSD classified as belonging to the dissociative subtype exhibited greater grey matter volume in the right precentral and fusiform gyri as well as less volume in the right inferior temporal gyrus. Greater dissociation severity was associated with greater volume in the right middle frontal gyrus. CONCLUSION: The results of this first whole-brain investigation of specific grey matter volume in dissociative subtype PTSD indentified structural aberrations in regions subserving the processing and regulation of emotional arousal. These might constitute characteristic biomarkers for the dissociative subtype PTSD. PMID- 26138236 TI - Microcirculation in the foot is augmented by neuromuscular stimulation via the common peroneal nerve in different lower limb postures: a potential treatment for leg ulcers. AB - OBJECTIVES: To examine the effects of the gekoTM device (a portable electical nerve stimulator) on microcirculatory flow on the dorsum of the foot, and whether this is influenced by lower limb postures and application of a plaster cast. STUDY DESIGN: Cross-sectional, healthy cohort, open label, physiological response study. METHODS: In 10 healthy volunteers, aged 19 to 24 years, Laser Doppler Fluxmetry measurements were made on the dorsum of the foot in four postures: standing (weight bearing and non-weight bearing) and supine lying (with the lower limb horizontal and then elevated). Measurements of flux were made both at rest and during stimulation with the gekoTM device applied over the common peroneal nerve, at 1Hz for 5 minutes in each posture. Repeat measurement were made after the application of a below knee plaster cast. Measures of flux were compared to basal levels assumed to be in supine with limb horizontal, with no cast and an inactive Geko device. RESULTS: The gekoTM device was effective in increasing microcirculation on the dorsum of the foot in all four postures (Mean difference =141%, 95% CI 70%-212%, p=0.001). This effect was more pronounced than that of using a plaster alone (Mean increase in Flux of 73%, 95% CI 22%-125%, p=0.01) or variances due to the hydrostatic effects of different postures (Mean difference 17-27.6%, p>0.05). There was a 2 to 3 fold increase in flux when stimulation was delivered in combination with the plaster cast. CONCLUSIONS: Stimulation using the gekoTM device augments microcirculation in the foot. The response is greater in lying and non-weight bearing than weight bearing standing but the most striking effect is when stimulation is combined with a plaster cast. The gekoTM offers a potential means of promoting conditions favourable for wound healing, where treatment using compression may be contraindicated, such as arterial/mixed aetiology ulcers. PMID- 26138237 TI - Diagnosis, etiology and management of the Budd-Chiari Syndrome: a bloodcoagulation and hepatological study on the course of the disease treated with TIPS. AB - BACKGROUND: Budd-Chiari Syndrome (BCS) is characterized by obstruction of blood flow in hepatic veins. The aim of the study was to analyze diagnosis, etiology and management of BCS. METHODS: We analyzed 44 patients (32 females, 12 males, the mean age <35y of age) treated with TIPS. Ascites was found in 35 patients as the most frequent symptom. The median of total follow-up was 52 months. Non covered (bare) or covered stent was inserted to all patients. Diagnosis of myeloproliferative neoplasm (MPN) was based on WHO criteria. Other inherited or acquired thrombophilia were assessed as well. Therapy of BCS was with regard to the etiology. RESULTS: The etiology of BCS was identified in 38 cases. Ph- MPN was found as the most common risk factor (50%, N.=22), especially polycythemia vera. JAK2V617F mutation was detected in the most of 22 MPN cases (82.5%). The second most common etiologic factor was inherited thrombophilia (18%, N.=8). In the non-covered (bare) stent group, a primary patency rates 52.9% in 1 year and 20% in 5 years after TIPS (Portasystemic Shunt, Transjugular Intrahepatic) creation. In the covered stent group the 1-year and 5-year primary patency rates were was 80% and 33.3% respectively. The average 5-year re-intervention rate per patient was 1.65 procedures in the bare stent group and 0.67 in the covered stent group. Re-interventions were more frequent in MPN patients. All patients were anticoagulated with heparin at the beginning, switched to vitamin K antagonist. On top of TIPS, anticoagulant and a vigorous therapy of underlying disorder are necessary. CONCLUSION: BCS is a serious and life-threatening disorder in MPD is a major cause of morbidity and mortality. Therapy requires a multidisciplinary approach. Insertion of TIPS dedicated covered stent is a very effective treatment in cases resistant to conservative approach with lower dysfunction rate and the number of re-interventions. PMID- 26138238 TI - Blood absorption during 970 and 1470 nm laser radiation in vitro. AB - AIM: Soon after introduction of water lasers in medical practice for EVLA, less power and energy line density have been used. However, there are no experimental grounds for different energy modes and there is no clear evidence for a difference in the effect of the two wavelengths dealt with in this study. The goal of this study was to evaluate the temperature profile of various laser action modes with testing devices. METHODS: Three experimental testing devices consisted of cylinders filled with whole donor blood and a set of temperature sensors installed in different positions. RESULTS: We have determined the range of temperatures around the fiber tip of 970 and 1470 nm lasers. The average temperature of 970 nm laser at 1 mm distance along the axis from the fiber tip substantially differed from that of 1470 nm laser, power being equal. CONCLUSION: Statistically substantial differences were found in endovenous laser ablation simulation in vitro for the 970 nm and 1470 nm laser radiation. Similar temperatures can be reached with 970 nm lasers if power is increased. PMID- 26138239 TI - Increased FGF1-FGFRc expression in idiopathic pulmonary fibrosis. AB - BACKGROUND: Recent clinical studies show that tyrosine kinase inhibitors slow the rate of lung function decline and decrease the number of acute exacerbations in patients with Idiopathic Pulmonary Fibrosis (IPF). However, in the murine bleomycin model of fibrosis, not all tyrosine kinase signaling is detrimental. Exogenous ligands Fibroblast Growth Factor (FGF) 7 and 10 improve murine lung repair and increase survival after injury via tyrosine kinase FGF receptor 2b signaling. Therefore, the level and location of FGF/FGFR expression as well as the exogenous effect of the most highly expressed FGFR2b ligand, FGF1, was analyzed on human lung fibroblasts. METHODS: FGF ligand and receptor expression was evaluated in donor and IPF whole lung homogenates using western blotting and qPCR. Immunohistochemistry for FGF1 and FGFR1/2/3/4 were performed on human lung tissue. Lastly, the effects of FGF1, a potent, multi-FGFR ligand, were studied on primary cultures of IPF and non-IPF donor fibroblasts. Western blots for pro fibrotic markers, proliferation, FACS for apoptosis, transwell assays and MetaMorph analyses on cell cultures were performed. RESULTS: Whole lung homogenate analyses revealed decreased FGFR b-isoform expression, and an increase in FGFR c-isoform expression. Of the FGFR2b-ligands, FGF1 was the most significantly increased in IPF patients; downstream targets of FGF-signaling, p ERK1/2 and p-AKT were also increased. Immunohistochemistry revealed FGF1 co localization within basal cell sheets, myofibroblast foci, and Surfactant protein C positive alveolar epithelial type-II cells as well as co-localization with FGFR1, FGFR2, FGFR3, FGFR4 and myofibroblasts expressing the migratory marker Fascin. Both alone and in the presence of heparin, FGF1 led to increased MAPK signaling in primary lung fibroblasts. While smooth muscle actin was unchanged, heparin + FGF1 decreased collagen production in IPF fibroblasts. In addition, FGF1 + heparin increased apoptosis and cell migration. The FGFR inhibitor (PD173074) attenuated these effects. CONCLUSIONS: Strong expression of FGF1/FGFRs in pathogenic regions of IPF suggest that aberrant FGF1-FGFR signaling is increased in IPF patients and may contribute to the pathogenesis of lung fibrosis by supporting fibroblast migration and increased MAPK-signaling. PMID- 26138240 TI - Inflammatory response of cultured rat synoviocytes challenged with synovial fluid from osteoarthritis patients correlates with their radiographic grading: a pilot study. AB - The inflammatory nature of synovial fluid (SF) of varying grade osteoarthritis (OA) patients was estimated by measuring pro-inflammatory factors and through a unique cell-challenge experiment. SF samples were collected from six OA and one non-OA patient; spanning Kellgren-Lawrence (KL) grades were analyzed for interlukin-1-beta (IL-1beta), nitric oxide (NO) and its derivatives, and glycosaminoglycan (GAG). Levels of IL-1beta, NO, and GAG in SF did not correlate with KL grades of the patients studied. In the cell-challenge experiment, cultured rat synoviocyte fibroblasts (RSFs) were challenged by the patient's SFs with and without pre-treatment of IL-1beta and lipopolysaccharide (LPS). NO released by the cells was taken as an indicator of inflammation. SFs from KL grades 2 and 3 induced maximum inflammation in cultured RSFs (grade 2 64.61 +/- 4.8 and 89.51 +/- 5.6 MUM/ml after 48 and 72 h, grade 3 58.27 +/- 2.7 and 64.22 +/- 2.8 MUM/ml after 48 and 72 h, respectively). Similar trend was observed in RSF pretreated with either recombinant IL-1beta or LPS suggesting that SF from patients KL grades 2 and 3 accumulates more pro-inflammatory factors. IL-1beta pre-treated RSFs challenged by SF for 72 h showed 234.41 +/- 17.6 MUM/ml increase (patient 3, grade 3), whereas higher NO after LPS pre-treatment was recorded (118.92 +/- 6.2 MUM/ml; patient 3, grade 3). Interestingly, SFs from grade 1 and non-OA patient could reduce released NO to 27.10 +/- 2.2 MUM/ml showing potency to alleviate inflammation. These interesting findings, however, need to be confirmed on a wider number of patients, which may offer significant therapeutic application in treatment of OA. PMID- 26138241 TI - Primary cell culture method for the honeybee Apis mellifera. AB - Honeybees are among the most important pollinators in nature, and honeybee associated products are useful in various areas, including the food industry. However, honeybees may be infected by various types of pathogens. The study of honeybee-associated diseases would greatly benefit from a successful cell culture system, but although some honeybee cell culture techniques have been introduced, these methods have not yet been fully established. Here, we describe a primary cell culture method for the honeybee, Apis mellifera. We isolated, sterilized, and seeded egg cells into non-coated cell culture dishes to generate cell aggregates. After approximately 10 d, aggregates were dissociated and seeded to cell culture dishes. Cell passages were continuously performed, with sub culturing every 3-4 d. The cells expressed non-adherent phenotypes. Their growth increased with the passage number when they were cultured in growth medium based on L-15 insect medium but not Schneider's insect medium. Finally, polymerase chain reaction confirmed that the cells originated from A. mellifera. Our results suggest that the culturing methods described herein are appropriate for isolating primary cells from honeybee eggs. These methods could thus facilitate the study of honeybee-associated pathogenesis, development, and toxicology. PMID- 26138242 TI - Nucleostemin exerts anti-apoptotic function via p53 signaling pathway in cardiomyocytes. AB - Cardiomyocytes apoptosis following reperfusion injury causes irreversible damage to cardiac function. Understanding the mechanisms underlying cardiomyocytes death under these conditions can be helpful to identify strategies to abrogate such detrimental effects. Stem cell-specific proteins and regulatory pathways become important in understanding reparative processes in the myocardium. One such regulatory protein named nucleostemin (NS) has vital roles in cardiac ischemia. Although the relationship between NS and cell apoptosis has been studied, it is unknown how NS is controlled and how it participates in cardiomyocytes apoptosis induced by ischemia reperfusion (I/R). In the present study, we aimed to investigate the direct role of NS in myocardial I/R. In vivo, NS was highly expressed in cardiac tissues after I/R. Double immunofluorescent staining showed that NS located in the nucleolar of cardiomyocytes and correlated with cardiomyocytes apoptosis. Furthermore, in vitro primary rat cardiomyocytes increased NS expression induced by hypoxia-reoxygenation (H/R) treatment, in line with results in vivo. Suppression of NS expression by siNS promoted the expression of terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL)-positive cells p53 and cleaved caspase-3, which demonstrates I/R may require increased expression of NS to suppress p53 activation and maintain cardiomyocytes survival. PMID- 26138243 TI - CADASIL with Multiorgan Involvement: a Complete Autopsy Examination Report. PMID- 26138244 TI - Hepatocellular nodules resulting from congenital extrahepatic portosystemic shunts can differentiate into potentially malignant hepatocellular adenomas. AB - BACKGROUND: Hepatocellular nodules caused by congenital extrahepatic portosystemic shunts (CEPS) occur as a result of abnormal portal blood flow, and are mostly cases of benign focal nodular hyperplasia (FNH). However, hepatocellular adenomas (HCA) and hepatocellular carcinomas have been documented in the CEPS patients. HCA can now be immunohistochemically diagnosed; therefore, the concept of hepatocellular nodules resulting from CEPS should be revisited. In this study, we performed a retrospective immunohistochemical investigation of hepatocellular nodules from livers isolated from the CEPS patients undergoing living donor liver transplantation (LDLT). METHODS: Hepatocellular nodules from livers of five patients with CEPS who underwent LDLT between June 2004 and October 2012 at our institution were immunohistochemically investigated. HCA were classified into four subtypes (HNF1alpha-inactivated HCA (H-HCA); inflammatory HCA; beta-catenin-activated HCA (b-HCA); unclassified HCA). RESULTS: Sixteen hepatocellular nodules were collected from livers of five patients with CEPS who underwent LDLT. Ten hepatocellular nodules were categorized as FNH (62.5%), five were categorized as b-HCA (31.3%), and one was categorized as H-HCA (6.2%). CONCLUSIONS: Some of the hepatocellular nodules resulting from CEPS were indicative of HCAs, especially the b-HCA subtype which has the potential for malignant transformation. Surgical or interventional treatments might have to be performed when hepatocellular nodules appear in the CEPS patients. PMID- 26138245 TI - Pregnancy following Mustard or Senning correction of transposition of the great arteries: a retrospective study. AB - OBJECTIVE: To determine pregnancy outcome in women with atrial switch repair for transposition of the great arteries (TGA) and to compare follow up with a control group of childless women with the same repair. DESIGN: Retrospective cohort study. SETTING: Tertiary care medical centre. POPULATION: About 21 patients compared with 15 controls. METHODS: Review of records from joint cardiac obstetric clinic 1993-2013. MAIN OUTCOME MEASURES: Occurrence of cardiovascular events: maternal death, heart failure, arrhythmia, thromboembolic events, worsening systemic ventricular function, worsening tricuspid valve regurgitation and newly detected baffle problems. RESULTS: There were 34 pregnancies in 21 women. Mean follow up was 100 months. No deaths or recurrence occurred. Events (few arrhythmias, thromboembolic events and baffle issues) were common in both groups: 13 (62%) patients and eight (53%) controls (P = 0.736). Worsening of ventricular function was similar in both groups: six (29%) patients and four (27%) controls (P = 0.899). Worsening tricuspid regurgitation was more common in patients [11 (52%)] than controls (0)] (P < 0.001). Labour was induced in 76% cases: 32% for cardiac deterioration, 37% to control timing of delivery, and 26% for intrauterine growth restriction. Delivery was vaginal in 84% cases. Median gestational age was 37 (30-40) weeks, median birthweight 2525 g (1460-3530). In all, 38% babies were premature and 38% were small-for-gestational-age. CONCLUSIONS: Cardiac events after atrial repair for TGA are equally common in pregnant women and non-pregnant controls, although worsening tricuspid regurgitation occurs more frequently in pregnancy. Induction of labour is to be expected but vaginal delivery is achievable in most cases. Infants are likely to be premature and small-for-gestational-age. TWEETABLE ABSTRACT: Pregnancy in atrial repair for TGA: cardiac events similar to controls, prematurity and small babies likely. PMID- 26138246 TI - Lower Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor Predicts Progression from Mild Cognitive Impairment to Alzheimer's Disease. AB - There is little information on the dynamics of BDNF in the CSF in the continuum between healthy aging, MCI and AD. We included 128 older adults (77 with amnestic MCI, 26 with AD and 25 healthy controls). CSF BDNF level was measured by ELISA assay, and AD biomarkers (Abeta42, T-Tau and P-Tau181) were measured using a Luminex xMAP assay. CSF BDNF levels were significantly reduced in AD subjects compared to MCI and healthy controls (p = 0.009). Logistic regression models showed that lower CSF BDNF levels (p = 0.008), lower CSF Abeta42 (p = 0.005) and lower MMSE scores (p = 0.007) are significantly associated with progression from MCI to AD. The present study adds strong evidence of the involvement of BDNF in the pathophysiology of neurodegenerative changes in AD. Interventions aiming to restore central neurotrophic support may represent future therapeutic targets to prevent or delay the progression from MCI to AD. PMID- 26138247 TI - CTRP3 attenuates post-infarct cardiac fibrosis by targeting Smad3 activation and inhibiting myofibroblast differentiation. AB - C1q/tumor necrosis factor-related protein-3 (CTRP3) is a novel adipokine with modulation effects on metabolism, inflammation, and cardiovascular system. This study aimed to investigate the effect of CTRP3 on cardiac fibrosis and its underlying mechanism. The myocardial expression of CTRP3 was significantly decreased after myocardial infarction (MI). Adenovirus-delivered CTRP3 supplement attenuated myocardial hypertrophy, improved cardiac function, inhibited interstitial fibrosis, and decreased the number of myofibroblasts post-MI. In cultured adult rat cardiac fibroblasts (CFs), CTRP3 attenuated cell proliferation; migration; and the expression of connective tissue growth factor, collagen I, and collagen III induced by transforming growth factor (TGF)-beta1. Moreover, CTRP3 inhibited whereas CTRP3 small interfering RNA (siRNA) facilitated the expression of alpha-SMA and profibrotic molecules induced by TGF-beta1. CTRP3 also attenuated TGF-beta1-induced Smad3 phosphorylation, nuclear translocation, and interaction with p300. CTRP3 increased the phosphorylation of AMP-activated protein kinase (AMPK) and Akt in both rat hearts and CFs. Adenine 9-beta-D arabinofuranoside (AraA), an AMPK inhibitor, abolished the protective effect of CTRP3 against TGF-beta1-induced profibrotic response and Smad3 activation. Taken together, CTRP3 attenuates cardiac fibrosis by inhibiting myofibroblast differentiation and the subsequent extracellular matrix production. AMPK is required for the anti-fibrotic effect of CTRP3 through targeting Smad3 activation and inhibiting myofibroblast differentiation. KEY MESSAGE: CTRP3 alleviates cardiac fibrosis in a rat post-MI model and in cardiac fibroblasts. CTRP3 inhibits fibroblast-to-myofibroblast differentiation. CTRP3 exerts anti-fibrotic effect through targeting Smad3 activation. AMPK mediates the anti-fibrotic effect of CTRP3 by inhibition of Smad3 activation. PMID- 26138248 TI - Deletion of Panx3 Prevents the Development of Surgically Induced Osteoarthritis. AB - Osteoarthritis (OA) is a highly prevalent, disabling joint disease with no existing therapies to slow or halt its progression. Cartilage degeneration hallmarks OA pathogenesis, and pannexin 3 (Panx3), a member of a novel family of channel proteins, is upregulated during this process. The function of Panx3 remains poorly understood, but we consistently observed a strong increase in Panx3 immunostaining in OA lesions in both mice and humans. Here, we developed and characterized the first global and conditional Panx3 knockout mice to investigate the role of Panx3 in OA. Interestingly, global Panx3 deletion produced no overt phenotype and had no obvious effect on early skeletal development. Mice lacking Panx3 specifically in the cartilage and global Panx3 knockout mice were markedly resistant to the development of OA following destabilization of medial meniscus surgery. These data indicate a specific catabolic role of Panx3 in articular cartilage and identify Panx3 as a potential therapeutic target for OA. Lastly, while Panx1 has been linked to over a dozen human pathologies, this is the first in vivo evidence for a role of Panx3 in disease. KEY MESSAGE: Panx3 is localized to cartilage lesions in mice and humans. Global Panx3 deletion does not result in any developmental abnormalities. Mice lacking Panx3 are resistant to the development of osteoarthritis. Panx3 is a novel therapeutic target for the treatment of osteoarthritis. PMID- 26138250 TI - Primary percutaneous coronary intervention in an anomalous single coronary trunk arising anomalously from ascending aorta. AB - A 45-year-old male patient presented with acute anterior wall myocardial infarction. Angiography revealed a single coronary trunk arising from the ascending aorta above the coronary sinuses and giving rise to right coronary artery, left circumflex artery and critical stenosis in the left anterior descending artery. This report also highlights the feasibility of performing percutaneous coronary intervention (PCI) in this rare anomaly and discusses the important technical considerations to be kept in mind while attempting such a case. This is the first report of such an anomalous origin of a single coronary trunk arising from ascending aorta. PMID- 26138249 TI - Mitochondrial variants in MT-CO2 and D-loop instability are involved in MUTYH associated polyposis. AB - Mitochondrial DNA alterations have been widely reported in different human tumours, including colorectal carcinoma, but their mutational spectrum and pathogenic role in specific subsets of patients with polyposis syndromes have been poorly investigated. We compared the breadth of somatic variants across the mitochondrial genome of MUTYH-associated polyposis (MAP) patients with homogeneous groups of classical/attenuated familial adenomatous polyposis (FAP/AFAP) and sporadic cases. Overall, we screened 121 adenomas and seven adenocarcinomas and their corresponding germinal controls, for mitochondrial genes with a crucial role in oxidative phosphorylation and translation (MT-CO1, MT-CO2, MT-CO3, MT-TD, MT-TS1, MT-ATP6) as well as a hypervariable sequence (HV II) within the control region displacement loop (D-loop), a marker of hypermutability and clonal expansion. The sequencing analysis revealed the presence of 17 variants, mostly causing non-synonymous changes in conserved amino acid residues, typically distributed in the MT-CO2 gene of MAP patients (P < 0.0001), who frequently carried the hot spot m.7763G>A variant. Accordingly, D loop instability was also significantly associated with variants grouped inside the MT-CO2 gene (P = 0.0061). This is the first report showing a locus-specific distribution of mitochondrial DNA alterations in a subtype of colorectal tumourigenesis. In addition, our findings suggest that MT-CO2 variants, representing early molecular events in MAP tumorigenesis, might be a potential prognostic biomarker for the cancer-risk assessment of patients affected by this syndrome. KEY MESSAGES: We compared the frequencies of mtDNA variants in MAP vs. FAP/AFAP/sporadic patients. We found a gene-specific (MT-CO2) distribution of mtDNA variants in MAP cases. Most mtDNA variants caused non-synonymous changes in conserved amino acid residues. D-loop instability was significantly associated with variants grouped inside MT-CO2. MT-CO2 variants might be a potential prognostic biomarker in MAP patients. PMID- 26138251 TI - Impact of rare codons and the functional coproduction of rate-limiting tRNAs on recombinant protein production in Bacillus megaterium. AB - The Gram-positive bacterium Bacillus megaterium was systematically developed for the plasmid-based production of recombinant proteins at the gram-per-liter scale. The amount of protein produced per cell was found strongly correlated to the codon usage of the heterologous gene of interest in comparison to the codon usage of B. megaterium. For analyzing the influence of rare codons on the translational efficiency and protein production in B. megaterium, a test system using the gene for the green fluorescent protein (GFP) as reporter was established. For this purpose, four consecutive identical codons were introduced into the 5' end of gfp and the resulting variations in GFP formation were quantified. Introduction of the rare codons GCC, CGG, and ACC for alanine, arginine, and threonine reduced GFP production 2.1-, 3.3-, and 1.7-fold in comparison to the favored codons GCU, CGU, and ACA, respectively. Coexpression of the corresponding rare codon tRNA (rctRNA) genes improved GFP production 4.2-, 2.7-, and 1.7-fold, respectively. The system was applied to the production of a formate dehydrogenase (FDH) from Mycobacterium vaccae and an extracellular hydrolase (TFH) from Thermobifida fusca. Coexpression of one to three different rctRNA genes resulted in an up to 18-fold increased protein production. Interestingly, rctRNA gene coexpression also elevated the production of M. vaccae FDH and T. fusca TFH from codon optimized genes, indicating a general positive effect by rctRNA gene overexpression on the protein production in B. megaterium. Thus, the basis for a B. megaterium enhanced production strain coexpressing rctRNA genes was laid. PMID- 26138252 TI - First case report of staghorn calculi successfully removed by mini-endoscopic combined intrarenal surgery in a 2-year-old boy. AB - Less-invasive therapy for pediatric urolithiasis is available due to the miniaturization of equipment and improved optics; however, surgical treatment strategies, especially for large calculi, remain controversial. We describe here our experience of treating a 2-year-old boy with left renal staghorn calculi with a single session of mini-endoscopic combined intrarenal surgery in the prone split-leg position with pre-ureteral stenting and the directional enhanced flow imaging ultrasound technique. This is the first report of successful pediatric mini-endoscopic combined intrarenal surgery without any major complications. We believe this technique provides an important therapeutic option for large renal calculus in pediatric patients. PMID- 26138253 TI - Patterns of natural selection acting on the mitochondrial genome of a locally adapted fish species. AB - BACKGROUND: Mitochondrial DNA (mtDNA) is frequently used in population genetic studies and is usually considered as a neutral marker. However, given the functional importance of the proteins encoded by the mitochondrial genome, and the prominent role of mitochondria in cellular energy production, the assumption of neutrality is increasingly being questioned. RESULTS: We tested for evidence of selection on the mitochondrial genome of the Atlantic salmon, which is a locally adapted and widely farmed species and is distributed across a large latitudinal cline. We analysed 20 independent regions of the salmon mtDNA that represented nine genes (ND1, ND2, ND3, COX1, COX2, ATP6, ND4, ND5, and CYTB). These 20 mtDNA regions were sequenced using a 454 approach from samples collected across the entire European range of this species. We found evidence of positive selection at the ND1, ND3 and ND4 genes, which is supported by at least two different codon-based methods and also by differences in the chemical properties of the amino acids involved. The geographical distribution of some of the mutations indicated to be under selection was not random, and some mutations were private to artic populations. We discuss the possibility that selection acting on the Atlantic salmon mtDNA genome might be related to the need for increased metabolic efficiency at low temperatures. CONCLUSIONS: The analysis of sequences representing nine mitochondrial genes that are involved in the OXPHOS pathway revealed signatures of positive selection in the mitochondrial genome of the Atlantic salmon. The properties of the amino acids involved suggest that some of the mutations that were identified to be under positive selection might have functional implications, possibly in relation to metabolic efficiency. Experimental evidence, and better understanding of regional phylogeographic structuring, are needed to clarify the potential role of selection acting on the mitochondrial genome of Atlantic salmon and other locally adapted fishes. PMID- 26138255 TI - Advanced neuroprotection for brain ischemia: an alternative approach to minimize stroke damage. AB - Despite decades of research on neuroprotectants in the fight against ischemic stroke, no successful results have been obtained and new alternative approaches are urgently needed. Translation of effective candidate drugs in experimental studies to patients has systematically failed. However, some of those treatments or neuroprotectant diets which demonstrated only beneficial effects if given before (but not after) ischemia induction and discarded for conventional neuroprotection, could be rescued in order to apply an 'advanced neuroprotection strategy' (ADNES). Herein, the authors discuss how re-profiling those neuroprotective candidate drugs and diets with the best potential, some of which are mentioned in this article as an ADNES, may be a good approach for developing successful treatments that protect the brain against ischemic damage. This novel approach would try to protect the brain of patients who are at high risk of suffering a stroke, before damage occurs, in order to minimize brain injury by having the neuroprotectant drug or diet 'on board' if unfortunately stroke occurs. PMID- 26138254 TI - Nanofibrous spongy microspheres enhance odontogenic differentiation of human dental pulp stem cells. AB - Dentin regeneration is challenging due to its complicated anatomical structure and the shortage of odontoblasts. In this study, a novel injectable cell carrier, nanofibrous spongy microspheres (NF-SMS), is developed for dentin regeneration. Biodegradable and biocompatible poly(l-lactic acid)-block-poly(l-lysine) are synthesized and fabricated into NF-SMS using self-assembly and thermally induced phase separation techniques. It is hypothesized that NF-SMS with interconnected pores and nanofibers can enhance the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs), compared to nanofibrous microspheres (NF-MS) without pore structure and conventional solid microspheres (S-MS) with neither nanofibers nor pore structure. During the first 9 d in culture, hDPSCs proliferate significantly faster on NF-SMS than on NF-MS or S-MS (p < 0.05). Following in vitro odontogenic induction, all the examined odontogenic genes (alkaline phosphatase content, osteocalcin, bone sialoprotein, collagen 1, dentin sialophosphoprotein (DSPP)), calcium content, and DSPP protein content are found significantly higher in the NF-SMS group than in the control groups. Furthermore, 6 weeks after subcutaneous injection of hDPSCs and microspheres into nude mice, histological analysis shows that NF-SMS support superior dentin-like tissue formation compared to NF-MS or S-MS. Taken together, NF-SMS have great potential as an injectable cell carrier for dentin regeneration. PMID- 26138256 TI - A novel quality scoring system for the evaluation of individual colonoscopy: A multicenter retrospective study. AB - BACKGROUND AND AIM: It is essential to develop a novel evaluation system for the quality of individual colonoscopy and provide guidelines on whether and when to follow up the patient after the initial colonoscopy. This study aimed to establish and validate a scoring system for the quality of individual colonoscopy in terms of the adenoma miss rate (AMR). METHODS: Patients undergoing two consecutive colonoscopies within 90 days between 2009 and 2011 from different levels of hospitals in China were enrolled into this study. Potential risk factors for adenoma miss at the individual colonoscopy in a cohort of patients were evaluated in univariate and multivariate analyses. Corresponding scores for the procedure-related factors were generated based on their weights, and a scoring system was established and then validated by correlating the system with AMR. RESULTS: A total of 2093 patients were enrolled. Procedure-related factors at the individual colonoscopy (including bowel preparation and imaging methods), doctor experience, retroflexion, and withdrawal time were identified to be independent risk factors, and each of these factors was scored from 0 to 3. Then, a novel scoring system for the quality of individual colonoscopy (ranging from 0 to 9) was established, which was closely correlated with the AMRs in the establishment (adjusted R(2) = 0.845) and validation databases (adjusted R(2) = 0.733). CONCLUSIONS: The developed and validated evaluation system, consisting of procedure-related independent factors, successfully assesses the quality of individual colonoscopy in terms of AMRs. PMID- 26138257 TI - Near infrared in vivo flow cytometry for tracking fluorescent circulating cells. AB - The in vivo flow cytometry (IVFC) is now a powerful technique in biomedical research, especially for tracking specific cells in circulatory system. The current fluorescence-based IVFC is limited to visible spectrum, while near infrared (NIR) dyes have their advantages, such as deeper penetration, less absorption and less scattering for NIR fluorescence. Here, using an NIR in vivo flow cytometer with a 785 nm laser excitation, the measurement of fluorescent dye IR-780 labeled circulating cells is demonstrated. Representative peaks corresponding to NIR fluorescent circulating cells are detected and quantified. In addition, blood flow information, including the blood flow velocity and flow volume per unit time, is obtained. By simultaneous detection of IR-780 and enhanced green fluorescent protein (EGFP) signals from dual labeled cells, the IR 780 is shown to be a suitable fluorescent dye for multicolor detection by IVFC, including NIR. Thus, the IVFC is extended to the NIR range and shows potential application in biomedical research. PMID- 26138258 TI - Investigation of Lung Involvement in Connective Tissue Disorders. AB - Lung involvement in connective tissue disorders (CTDs) may present as pleomorphic since any lung compartment may be involved such as airways, exocrine secretory and alveolar epithelia, interstitial lung structure, pulmonary vasculature and pleura as well as, in specific disorders, several tissues of the thoracoabdominal ventilator pump. Any combination of the above anatomic structures may be involved concomitantly although some specific combinations may include a determinant of rheumatic disorders. The diagnosis of a specific CTD requires the fulfilment of clearly defined clinical and laboratory criteria including in most cases positivity for autoantibodies, mostly specific serologic combinations. In this setting, serologic investigation targets mainly, although not exclusively, the detection of antinuclear antibodies. A specific serologic positivity or a combination of autoantibodies constitutes not only a diagnostic criterion for a specific CTD, but may also characterize the pattern of respiratory manifestation in a determinant rheumatic disorder. Therefore, the investigation of lung involvement in CTDs requires adequate skills in the ambit of a multidisciplinary approach and an extended spectrum of diagnostic tools and modalities able to detect both early clinical clues and serologic conversion as well as any pathophysiologic alteration that regards the complexity of respiratory functional status. Although many patients with CTDs suffer from a 'vicious' combination of lung involvement, lung drug toxicity and infections related to the above two as well as to the 'mater' disease, for space reasons this review will focus on the established lung manifestations that regard the 7 major CTDs. PMID- 26138259 TI - The Safety of Eplerenone in Hemodialysis Patients: A Noninferiority Randomized Controlled Trial. AB - BACKGROUND AND OBJECTIVES: Mineralocorticoid receptor antagonism reduces morbidity and mortality in patients with heart failure, but the safety of these drugs in patients receiving dialysis is unclear. This study evaluated whether hyperkalemia and/or hypotension limited the use of eplerenone, a selective mineralocorticoid receptor antagonist, in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a randomized controlled trial of prevalent patients receiving hemodialysis at five Canadian centers. Participants were randomly allocated to 13 weeks of eplerenone titrated to 50 mg daily (n=77) or a matching placebo (n=77). The primary outcome was permanent discontinuation of the drug because of hyperkalemia or hypotension. Secondary outcomes included hyperkalemia, hypotension, and cardiovascular events. RESULTS: Seventy-five eplerenone-treated patients and 71 placebo-treated patients were included in the per protocol population. The primary outcome occurred in three patients (4.0%) in the eplerenone group and two (2.8%) in the placebo group, for an absolute risk difference of 1.2 percentage points (95% confidence interval, -4.7 to 7.1 percentage points). Eplerenone was interpreted as noninferior to placebo with respect to the primary outcome (i.e., a discontinuation rate for these reasons >10% was excluded). In the eplerenone group, nine patients (11.7%) developed hyperkalemia (potassium level >6.5 mEq/L), compared with two patients (2.6%) in the placebo group (relative risk, 4.5; 95% confidence interval, 1.0 to 20.2). There was no significant effect on predialysis or postdialysis BP. CONCLUSION: Eplerenone increased the risk of hyperkalemia but did not result in an excess need to permanently discontinue the drug. Further trials are required to determine whether mineralocorticoid receptor antagonism improves cardiovascular outcomes in patients receiving long-term dialysis. PMID- 26138260 TI - Promoting Kidney Function Recovery in Patients with AKI Requiring RRT. AB - AKI requiring RRT is associated with high mortality, morbidity, and long-term consequences, including CKD and ESRD. Many patients never recover kidney function; in others, kidney function improves over a period of many weeks or months. Methodologic constraints of the available literature limit our understanding of the recovery process and hamper adequate intervention. Current management strategies have focused on acute care and short-term mortality, but new data indicate that long-term consequences of AKI requiring RRT are substantial. Promotion of kidney function recovery is a neglected focus of research and intervention. This lack of emphasis on recovery is illustrated by the relative paucity of research in this area and by the lack of demonstrated effective management strategies. In this article the epidemiologic implications of kidney recovery after AKI requiring RRT are discussed, the available literature and its methodologic constraints are reviewed, and strategies to improve the understanding of factors that affect kidney function recovery are proposed. Measures to promote kidney function recovery are a serious unmet need, with a great potential to improve short- and long-term patient outcomes. PMID- 26138263 TI - Developmental Dynamic Analysis of the Excreted Microbiome of Chickens Using Next Generation Sequencing. AB - Poultry contamination can be largely attributed to the presence of chicken feces during the production process. Fecal contamination is often found in raw chicken products sold for human consumption. Quantitative analysis of the fecal microbial community of chickens using next-generation sequencing techniques is the focus of this study. Fecal samples were collected from 30 broiler chickens at two time points: days 1 and 35 of development. 454 pyrosequencing was conducted on 16S rRNA extracted from each sample, and microbial population dynamics were investigated using various automated bioinformatics pipelines. Diversity of the microbial community at the genus level increased during the 5-week growth period. Despite this growth, only a few dominant bacteria groups (over 80%) were identified in each fecal sample, with most groups being unique and only a few were shared between samples. Population analysis at the genus level showed that microbial diversity increased with chicken growth and development. Classification and phylogenetic analysis of highly represented microbes (over 1%) clearly showed high levels of sequence similarity between groups such as Firmicutes and Proteobacteria. These results suggest that the chicken fecal excreted microbiome is a dynamic system with a differentiated population structure that harbors a highly restricted number of higher taxa. PMID- 26138262 TI - Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension. AB - BACKGROUND AND OBJECTIVES: The plasma concentration of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) associates with sympathetic activity in patients with CKD, but the driver of this association is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this longitudinal study (follow-up: 2 weeks-6 months), repeated measurements over time of muscle sympathetic nerve activity corrected (MSNAC), plasma levels of ADMA and symmetric dimethylarginine (SDMA), and BP and heart rate were performed in 14 patients with drug-resistant hypertension who underwent bilateral renal denervation (enrolled in 2013 and followed-up until February 2014). Stability of ADMA, SDMA, BP, and MSNAC over time (6 months) was assessed in two historical control groups of patients maintained on stable antihypertensive treatment. RESULTS: Time integrated changes in MSNAC after renal denervation ranged from -40.6% to 10% (average, -15.1%), and these changes were strongly associated with the corresponding changes in plasma ADMA (r= 0.62, P=0.02) and SDMA (r=0.72, P=0.004). Changes in MSNAC went along with simultaneous changes in standardized systolic (r=0.65, P=0.01) and diastolic BP (r=0.61, P=0.02). In the historical control groups, no change in ADMA, SDMA, BP, and MSNAC levels was recorded during a 6-month follow-up. CONCLUSIONS: In patients with resistant hypertension, changes in sympathetic activity after renal denervation associate with simultaneous changes in plasma levels of the two major endogenous methylarginines, ADMA and SDMA. These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition. PMID- 26138261 TI - Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan Africa. AB - CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age <1 to 74 years across a broad spectrum of kidney diseases secondary to hypertension-attributed nephropathy, diabetes, HIV infection, sickle cell disease, biopsy-proven glomerular disease, and CKD of unknown origin. Clinical and demographic data with biospecimens are collected to assess clinical, biochemical, and genetic markers of kidney disease. As of March 2015, a total of 3499 patients and controls have been recruited and 1897 had complete entry data for analysis. Slightly more than half (50.2%) of the cohort is female. Initial quality control of clinical data collection and of biosample and DNA analysis is satisfactory, demonstrating that a clinical research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa. PMID- 26138264 TI - Thymic carcinoma patients with myasthenia gravis exhibit better prognoses. AB - BACKGROUND: Thymic carcinoma is an aggressive mediastinal neoplasm with a poor prognosis, but the factors that contribute to its prognosis are not completely understood. Myasthenia gravis (MG) can coexist with thymic carcinoma with low incidence, but the effect MG has on thymic carcinoma prognosis is unknown. Here, we investigated the prognostic factors of thymic carcinoma and the influence of MG on patients with this disease. METHODS: Between January 1996 and December 2012, 49 patients were diagnosed with thymic carcinoma and surgically treated at our institution. Clinical data and survival information were recorded and systematically reviewed. Kaplan-Meier survival curves were generated, and independent prognostic factors were identified by Cox's proportional hazard model. RESULTS: Complete resection was achieved in 30 patients (61.2 %), and incomplete resection was performed on the other 19 patients (38.8 %). Six of the 49 patients with thymic carcinoma also presented with MG (12.2 %). Interestingly, these 6 patients exhibited much better prognoses when compared to the other 43 patients. Patients with MG also had significantly smaller tumors (P = 0.045), earlier Masaoka stage (P = 0.048), and higher complete resection rates (P = 0.042). However, multivariate analysis demonstrated that complete resection was the only independent predictor for overall survival (OS) (P < 0.001). CONCLUSIONS: The OS of patients with thymic carcinoma depends on complete resection, but patients with MG also demonstrate improved prognoses. MG patients have higher rates of complete surgical resection, which may account for their better prognoses. Patients with MG have unique features that may aid in the clinical management of these patients. PMID- 26138265 TI - Clinical outcome of urachal cancer in Japanese patients. AB - BACKGROUND: The outcome of treatment of Japanese patients with urachal cancer is not well known. The purpose of this study is to clarify the characteristics and outcomes of Japanese patients with urachal cancer. MATERIALS AND METHODS: The medical records of patients with urachal cancer who were treated in our hospital between 1994 and 2014 were retrospectively reviewed and statistically analyzed. RESULTS: We found 28 patients who had been diagnosed with urachal cancer and treated in our hospital during the study period. The median age of these patients was 52.3 years [interquartile range (IQR), 46.0-56.8 years]. Seventeen patients underwent surgery in our department. The median observation period of these patients was 42.6 months (IQR, 21.1-49.7 months). Among patients who had undergone surgery, cancer recurred in 7 (41 %). The estimated median time from surgery to recurrence and overall survival (OS) period were 35.8 months [95 % confidence interval (CI), 7.7 months-not determined] and not reached, respectively. Seventeen patients received chemotherapy for metastatic disease. The estimated median OS time from initial metastasis was 23.5 months (95 % CI, 11.8-33.3 months). CONCLUSIONS: Urachal cancer is usually locally advanced at presentation and it has a high risk of distant metastases. However, long-term survival following surgical treatment occurs in a significant fraction of patients. This study indicates the current treatment results for patients with urachal cancer in Japanese clinical practice. To establish a standard operation method and chemotherapy, a multicenter, prospective study is needed in a larger population in the future. PMID- 26138266 TI - (Epi)genotype-phenotype correlations in Beckwith-Wiedemann syndrome: a paradigm for genomic medicine. AB - Beckwith-Wiedemann syndrome (BWS) is the commonest overgrowth cancer predisposition disorder and represents a model for human imprinting dysregulation and tumorigenesis. BWS features can variably combine and present a widely variable range of severity in the phenotypic expression. This wide spectrum is paralleled at molecular level by complex (epi)genetic defects on chromosome 11p15.5 leading to disrupted expression of imprinted genes controlling growth and cellular proliferation. In this review, we outline the spectrum of clinical manifestations of BWS analyzing their (epi)genotype-phenotype correlations. The differences observed in the phenotypic profiles of BWS molecular subtypes allow a composite view of this syndrome with implications on clinical care, diagnosis, follow-up, and management, and provide directions for future disease monitoring. PMID- 26138267 TI - Conformational preferences of monohydrated clusters of imidazole derivatives revisited. AB - We present the IR spectroscopic investigations of benzimidazole (BIM), N methylbenzimidazole (MBIM), and their monohydrates (W1) carried out in a supersonic jet in the region of N-H, C-H, and O-H stretching fundamentals. The C H stretching modes in the monomers were studied with the aim of identifying the C(2)H mode (the C atom between the two N atoms in the imidazole moiety) which is known to play an important role as a H-bond donor in enzymes and ionic liquids. The assignment was aided by quantum chemical calculations as well as the literature data for FTIR measurements in the matrix. The monohydrated clusters were investigated for a global comparison with previously reported conformations of hydrated imidazole and related derivatives in the gas phase, matrices, and He nanodroplets. The BIM-W1 complex showed the presence of three conformers; an N H???O bound conformer (A') and two O-H???N bound conformers, tilted towards the phenyl side (A) and the imidazole side (B), respectively. Although both A' and B type conformers have been reported in the literature, our experiments identify a new conformer (conformer A) in the gas phase for the first time which has also been reported in crystal structures of histidine containing proteins. The binding energies of the three conformers were found to be of comparable magnitude, with the N-HO bound structure lying in between (~0.02-0.04 kcal mol(-1)) the O-H???N bound ones at the counterpoise corrected (cp) MP2/aug-cc-pVDZ level of theory. The formation of two distinct but closely related O-H???N bound conformers (A and B) was additionally confirmed by studying the MBIM-W1 complex. Binding energies of the MBIM-W1 conformers were found to be higher than those of the analogous BIM W1 conformers by 0.2 kcal mol(-1) at the cp-MP2/aug-cc-pVDZ level. The C(2)-H???O or pi bound water structures were not observed in the beam for monohydrated clusters of either monomer. While QTAIM calculations predicted secondary stabilization in the A type conformer by a C(4)-HO hydrogen bond, such an effect due to a possible C(2)-HO interaction was not found for conformer B. Experimentally, however, no spectral evidence was found for either the C(4)-H???O or the C(2)-H???O interaction. PMID- 26138268 TI - Ultra-structural hair alterations in Friedreich's ataxia: A scanning electron microscopic investigation. AB - Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder involving progressive damage to the central and peripheral nervous systems and cardiomyopathy. FRDA is caused by the silencing of the FXN gene and reduced levels of the encoded protein, frataxin. Frataxin is a mitochondrial protein that functions primarily in iron-sulfur cluster synthesis. Skin disorders including hair abnormalities have previously been reported in patients with mitochondrial disorders. However, to our knowledge, ultra-structural hair alterations in FRDA were not demonstrated. The purpose of this study was to determine ultra structural alterations in the hairs of FRDA patients as well as carriers. Hair specimen from four patients, who are in different stages of the disease, and two carriers were examined by scanning electron microscope. Thin and weak hair follicles with absence of homogeneities on the cuticular surface, local damages of the cuticular layer, cuticular fractures were detected in both carriers and patients, but these alterations were much more prominent in the hair follicles of patients. In addition, erosions on the surface of the cuticle and local deep cavities just under the cuticular level were observed only in patients. Indistinct cuticular pattern, pores on the cuticular surface, and presence of concavities on the hair follicle were also detected in patients in later stages of the disease. According to our results, progression of the disease increased the alterations on hair structure. We suggest that ultra-structural alterations observed in hair samples might be due to oxidative stress caused by deficient frataxin expression in mitochondria. PMID- 26138269 TI - Aryne-Induced Novel Tandem 1,2-Addition/(3+2) Cycloaddition to Generate Imidazolidines and Pyrrolidines. AB - A new "single-flask" method was developed for the synthesis of imidazolidines and pyrrolidines with high stereoselectivity. First, a Schiff base was arylated with an aryne. Second, an intramolecular proton transfer took place from the methylene position to the anionic aryne ring. Third, the resultant ylide reacted with a second equivalent of the same Schiff base in situ or an electron-deficient alkene through a (3+2) cycloaddition. These sequential tandem 1,2-addition/(3+2) cycloaddition reactions led to the desired heterocycles in 63-88% yields. PMID- 26138270 TI - Influence of copper oxide nanoparticle form and shape on toxicity and bioaccumulation in the deposit feeder, Capitella teleta. AB - Few in vivo studies have been conducted to assess how nanoparticle (NP) characteristics such as particle form and shape affect their toxicity and bioaccumulation. In the present study, the deposit feeder, Capitella teleta, was used to investigate the influence of copper form (CuO NPs, micron-sized CuO particles, and aqueous Cu) and CuO NP shape (spheres, rods and platelets) on toxicity and bioaccumulation through sediment exposures of approximately 250 MUg Cu/g dw sed. There were no effects of nanoparticle form or shape on mortality or growth rate during the exposure period. However, mortality increased to approximately 26.3% on average in all Cu treatments after the depuration period indicating a delayed effect of Cu exposure, despite more than 90% depuration of Cu during this period. A significant effect of nanoparticle shape was detected on body burden, the gross uptake rate constant and the depuration rate constant, suggesting preferential accumulation of rods by the worms. We recommend that additional sublethal endpoints and longer exposure durations should be examined to fully understand the environmental risks of CuO nanoparticles compared to other forms of Cu entering marine sediment systems. PMID- 26138271 TI - Prevalence and Severity of Dementia in Nursing Home Residents. AB - BACKGROUND/AIMS: The aim of this study was to compare the presence and severity of dementia in two large cross-sectional samples of nursing home residents from 2004/2005 and 2010/2011. METHODS: Demographic information as well as data on the type of nursing home unit, length of stay before assessment, physical health, regularly used prescribed drugs and Clinical Dementia Rating scale scores were used in the analyses. Logistic and linear regression models for hierarchical data were estimated. RESULTS: The odds of the occurrence and of a greater severity of dementia were higher in 2010/2011 than in 2004/2005. Independent of the time of study, married men had more severe dementia than single men, and single women had more severe dementia than single men. CONCLUSION: The findings may reflect the increase in the need for more nursing home beds designed for people with dementia between 2004/2005 and 2010/2011. PMID- 26138273 TI - Long-term neurodevelopmental outcome in high-risk newborns in resource-limited settings: a systematic review of the literature. AB - BACKGROUND: Improving outcomes beyond survival for high-risk newborns in resource limited settings is an emerging challenge. Global estimates demonstrate the scale of this challenge and significant gaps in morbidity outcome data in high mortality contexts. A systematic review was conducted to document the prevalence of neurodevelopmental impairment in high-risk newborns who were followed up into childhood in low- and middle-income countries. METHODS: High-risk newborns were defined as low, very or extremely low birthweight, preterm infants or those surviving birth asphyxia or serious infections. Electronic databases were searched and articles screened for eligibility. Included articles were appraised according to STROBE criteria. Narrative review was performed and median prevalence of key neurodevelopmental outcomes was calculated where data quality allowed. RESULTS: 6959 articles were identified with sixty included in final review. At follow-up in early childhood, median estimated prevalence (inter quartile range) of overall neurodevelopmental impairment, cognitive impairment and cerebral palsy were: for survivors of prematurity/very low birthweight 21.4% (11.6-30.8), 16.3% (6.3-29.6) and 11.2% (5.9-16.1), respectively, and for survivors of birth asphyxia 34.6% (25.4-51.5), 11.3% (7.7-11.8) and 22.8% (15.7 31.4), respectively. Only three studies reporting outcomes following newborn serious bacterial infections were identified. There was limited reporting of important outcomes such as vision and hearing impairment. Major challenges with standardised reporting of key exposure and developmental outcome variables and lack of control data were identified. CONCLUSION: Understanding the limitations of the available data on neurodevelopmental outcome in newborns in resource limited settings provides clear direction for research and efforts to improve long-term outcome in high-risk newborns in these settings. PMID- 26138272 TI - Cell-selective labelling of proteomes in Drosophila melanogaster. AB - The specification and adaptability of cells rely on changes in protein composition. Nonetheless, uncovering proteome dynamics with cell-type-specific resolution remains challenging. Here we introduce a strategy for cell-specific analysis of newly synthesized proteomes by combining targeted expression of a mutated methionyl-tRNA synthetase (MetRS) with bioorthogonal or fluorescent non canonical amino-acid-tagging techniques (BONCAT or FUNCAT). Substituting leucine by glycine within the MetRS-binding pocket (MetRS(LtoG)) enables incorporation of the non-canonical amino acid azidonorleucine (ANL) instead of methionine during translation. Newly synthesized proteins can thus be labelled by coupling the azide group of ANL to alkyne-bearing tags through 'click chemistry'. To test these methods for applicability in vivo, we expressed MetRS(LtoG) cell specifically in Drosophila. FUNCAT and BONCAT reveal ANL incorporation into proteins selectively in cells expressing the mutated enzyme. Cell-type-specific FUNCAT and BONCAT, thus, constitute eligible techniques to study protein synthesis-dependent processes in complex and behaving organisms. PMID- 26138276 TI - The ability of in vitro antioxidant assays to predict the efficiency of a cod protein hydrolysate and brown seaweed extract to prevent oxidation in marine food model systems. AB - BACKGROUND: The ability of different in vitro antioxidant assays to predict the efficiency of cod protein hydrolysate (CPH) and Fucus vesiculosus ethyl acetate extract (EA) towards lipid oxidation in haemoglobin-fortified washed cod mince and iron-containing cod liver oil emulsion was evaluated. The progression of oxidation was followed by sensory analysis, lipid hydroperoxides and thiobarbituric acid-reactive substances (TBARS) in both systems, as well as loss of redness and protein carbonyls in the cod system. RESULTS: The in vitro tests revealed high reducing capacity, high DPPH radical scavenging properties and a high oxygen radical absorbance capacity (ORAC) value of the EA which also inhibited lipid and protein oxidation in the cod model system. The CPH had a high metal chelating capacity and was efficient against oxidation in the cod liver oil emulsion. CONCLUSION: The results indicate that the F. vesiculosus extract has a potential as an excellent natural antioxidant against lipid oxidation in fish muscle foods while protein hydrolysates are more promising for fish oil emulsions. The usefulness of in vitro assays to predict the antioxidative properties of new natural ingredients in foods thus depends on the knowledge about the food systems, particularly the main pro-oxidants present. PMID- 26138277 TI - Navigable networks as Nash equilibria of navigation games. AB - Common sense suggests that networks are not random mazes of purposeless connections, but that these connections are organized so that networks can perform their functions well. One function common to many networks is targeted transport or navigation. Here, using game theory, we show that minimalistic networks designed to maximize the navigation efficiency at minimal cost share basic structural properties with real networks. These idealistic networks are Nash equilibria of a network construction game whose purpose is to find an optimal trade-off between the network cost and navigability. We show that these skeletons are present in the Internet, metabolic, English word, US airport, Hungarian road networks, and in a structural network of the human brain. The knowledge of these skeletons allows one to identify the minimal number of edges, by altering which one can efficiently improve or paralyse navigation in the network. PMID- 26138278 TI - De-Endothelialized Aortic Homografts: A Promising Scaffold Material for Tissue Engineered Heart Valves. AB - This study was designed to investigate the feasibility of de-endothelialized aortic homografts as a scaffold for tissue-engineered heart valves. Aortic homografts obtained from donor rabbits were treated either with collagenase to eliminate endotheliocytes or with the enzyme-detergent-nuclease method to remove all cell components. Then biomechanical properties of fresh, de-endothelialized and acellular homografts were investigated comparatively. The inflammation potential and immunogenicity were also assessed after allogenic transplantation. Expression of immune indices and inflammatory infiltration in de-endothelialized and acellular homografts were much weaker than in the controls, and no significant difference was observed between treated groups. However, heat shrinkage temperature, tensile strength and broken extension rate of acellular homografts decreased significantly compared to de-endothelialized ones. It is concluded that both de-endothelialization and thorough decellularization could reduce the immunogenicity and inflammation potential significantly, but the de endothelialized scaffold retained better structural strength. The de endothelialized aortic homograft might be a promising scaffold for tissue engineered heart valves. PMID- 26138279 TI - Population pharmacokinetics and dosing optimization of teicoplanin in children with malignant haematological disease. AB - AIM: Children with haematological malignancy represent an identified subgroup of the paediatric population with specific pharmacokinetic parameters. In these patients, inadequate empirical antibacterial therapy may result in infection related morbidity and increased mortality, making optimization of the dosing regimen essential. As paediatric data are limited, our aim was to evaluate the population pharmacokinetics of teicoplanin in order to define the appropriate dosing regimen in this high risk population. METHODS: The current dose of teicoplanin was evaluated in children with haematological malignancy. Population pharmacokinetics of teicoplanin were analyzed using nonmem software. The dosing regimen was optimized based on the final model. RESULTS: Eighty-five children (age range 0.5 to 16.9 years) were included. Therapeutic drug monitoring and opportunistic samples (n = 143) were available for analysis. With the current recommended dose of 10 mg kg(-1) day(-1) , 41 children (48%) had sub-therapeutic steady-state trough concentrations (Css,min <10 mg l(-1) ). A two compartment pharmacokinetic model with first order elimination was developed. Systematic covariate analysis identified that bodyweight (size) and creatinine clearance significantly influenced teicoplanin clearance. The model was validated internally. Its predictive performance was further confirmed in an external validation. In order to reach the target AUC of 750 mg l(-1) h 18 mg kg(-1) was required for infants, 14 mg kg(-1) for children and 12 mg kg(-1) for adolescents. A patient-tailored dose regimen was further developed and reduced variability in AUC and Css,min values compared with the mg kg(-1) basis dose, making the modelling approach an important tool for dosing individualization. CONCLUSIONS: This first population pharmacokinetic study of teicoplanin in children with haematological malignancy provided evidence-based support to individualize teicoplanin therapy in this vulnerable population. PMID- 26138280 TI - Sleep difficulties one year following mild traumatic brain injury in a population based study. AB - BACKGROUND: Sleep quality affects all aspects of daily functioning, and it is vital for facilitating recovery from illness and injury. Sleep commonly becomes disrupted following moderate to severe brain injury, yet little is known about the prevalence of sleep disruption over time and how it impacts on recovery following mild injury. METHODS: This was a longitudinal study of 346 adults who experienced a mild brain injury (aged >=16 years) identified within a population based incidence sample in New Zealand. The prevalence of sleep difficulties was assessed at baseline (within two weeks), one, six and 12 months, alongside other key outcomes. RESULTS: One year post injury, 41.4% of people were identified as having clinically significant sleep difficulties, with 21.0% at a level indicative of insomnia. Poor sleep quality at baseline was significantly predictive of poorer post-concussion symptoms, mood, community integration, and cognitive ability one year post injury. The prevalence of insomnia following mild traumatic brain injury (TBI) was more than three times the rate found in the general population. Of those completing a sleep assessment at six and 12 months, 44.9% of the sample showed improvements in sleep quality, 16.2% remained stable, and 38.9% worsened. CONCLUSIONS: Screening for sleep difficulties should occur routinely following a mild brain injury to identify adults potentially at risk of poor recovery. Interventions to improve sleep are needed to facilitate recovery from injury, and to prevent persistent sleep difficulties emerging. PMID- 26138281 TI - Altered processing of visual emotional stimuli in posttraumatic stress disorder: an event-related potential study. AB - Patients with posttraumatic stress disorder (PTSD) display abnormal emotional processing and bias towards emotional content. Most neurophysiological studies in PTSD found higher amplitudes of event-related potentials (ERPs) in response to trauma-related visual content. Here we aimed to characterize brain electrical activity in PTSD subjects in response to non-trauma-related emotion-laden pictures (positive, neutral and negative). A combined behavioral-ERP study was conducted in 14 severe PTSD patients and 14 controls. Response time in PTSD patients was slower compared with that in controls, irrespective to emotional valence. In both PTSD and controls, response time to negative pictures was slower compared with that to neutral or positive pictures. Upon ranking, both control and PTSD subjects similarly discriminated between pictures with different emotional valences. ERP analysis revealed three distinctive components (at ~300, ~600 and ~1000 ms post-stimulus onset) for emotional valence in control subjects. In contrast, PTSD patients displayed a similar brain response across all emotional categories, resembling the response of controls to negative stimuli. We interpret these findings as a brain-circuit response tendency towards negative overgeneralization in PTSD. PMID- 26138282 TI - Microsecond simulations of mdm2 and its complex with p53 yield insight into force field accuracy and conformational dynamics. AB - The p53-MDM2 complex is both a major target for cancer drug development and a valuable model system for computational predictions of protein-ligand binding. To investigate the accuracy of molecular simulations of MDM2 and its complex with p53, we performed a number of long (200 ns to 1 us) explicit-solvent simulations using a range of force fields. We systematically compared nine popular force fields (AMBER ff03, ff12sb, ff14sb, ff99sb, ff99sb-ildn, ff99sb-ildn-nmr, ff99sb ildn-phi, CHARMM22*, and CHARMM36) against experimental chemical shift data, and found similarly accurate results, with microsecond simulations achieving better agreement compared to 200-ns trajectories. Although the experimentally determined apo structure has a closed binding cleft, simulations in all force fields suggest the apo state of MDM2 is highly flexible, and able to sample holo-like conformations, consistent with a conformational selection model. Initial structuring of the MDM2 lid region, known to competitively bind the binding cleft, is also observed in long simulations. Taken together, these results show molecular simulations can accurately sample conformations relevant for ligand binding. We expect this study to inform future computational work on folding and binding of MDM2 ligands. PMID- 26138283 TI - Quality of life of patients with end-stage peritoneal metastasis treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). AB - BACKGROUND: Quality of Life (QoL) plays an important role in patients with peritoneal metastasis and is deteriorating continuously until death. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative palliative treatment of peritoneal metastasis. We present the first QoL results under PIPAC therapy. METHODS: Retrospective analysis of QLQ30 questionnaire results during repeated courses of PIPAC applications in palliative patients with pretreated peritoneal metastasis. RESULTS: 91 patients (M:F = 40:51, median age 64 (34-77) years) with 158 PIPAC applications were analyzed. 86% patients had previously received systemic chemotherapy. Peritoneal metastasis was advanced (Peritoneal Carcinomatosis Index I = 16 +/- 10). At admission, only moderate impairment of functioning (62-83%) and symptom scores (17-47%) was observed. 48 patients received at least 2 PIPAC every 6 weeks. After PIPAC # 1, the global physical score deteriorated slightly (from 82% to 75%), but improved after PIPAC # 2 (up to 89%). Gastrointestinal symptoms (nausea/vomiting, constipation, diarrhoea, anorexia) remained stable under PIPAC therapy. CONCLUSIONS: Quality of life was relatively high in this group of patients with advanced, pretreated peritoneal metastasis, explaining their wish for further therapy. Functioning scores and disease-related symptoms were not altered for at least 3 months in the patients able to receive repeated PIPAC. Except for a transient moderate increase of pain scores, PIPAC did not cause therapy-related QoL deterioration, especially no gastrointestinal symptoms. PMID- 26138284 TI - Outcome evaluation of an educational program for Japanese midwives to promote breast awareness for women. AB - AIM: The objective of this study was to evaluate educational approaches for midwives to promote breast awareness for postnatal women by measuring the knowledge, attitude and practice of midwives. METHODS: A nonequivalent control design comparing two intervention groups and control group was used. Participants were Japanese midwives agreeing to this study. Midwives in the program group attended the program; those in the text group only read the textbook. Midwives in the control group neither attended the program nor learned by textbook. All measurements were administered at baseline, one-month post-program, and three month post-program. RESULTS: Among 215 participants, 168 midwives (45 program, 62 text, and 61 control) remained until three month follow-up. The knowledge test score was found to have significant mutual interactions between the three groups and time (F=14.2, df=4, p<0.001). However, the attitudes did not differ between the three groups. Implementation rates for midwifery practice incorporating breast awareness education for postpartum women were different at one month and three months between the three groups. Implementation of breast awareness education at three months revealed the following factors: program group (OR 5.4, 95%CI [1.3-21.8]; text group: OR 0.7, 95%CI [0.2-2.7]) and implementation of breast awareness education at the first time measurement (OR 18.6, 95%CI [4.6 73.9]). CONCLUSIONS: The results of this study showed that the educational program increased midwives' knowledge and contributed to the continuation implementing breast awareness education for postpartum women about three months after testing. PMID- 26138285 TI - RF - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Treatment Update. PMID- 26138286 TI - Daylight photodynamic therapy. PMID- 26138287 TI - The flavonoid beverage Haelan 951 induces growth arrest and apoptosis in pancreatic carcinoma cell lines in vitro. AB - BACKGROUND: A major challenge in pancreatic cancer treatment is the resistance of human pancreatic cancer cells to apoptosis. Soy isoflavones and calpain inhibition have been suggested to exert inhibitory effects on cancer development and progression. We investigated the effects of the isoflavone containing beverage Haelan 951 and the calpain inhibitor PD150606 on the viability, growth and apoptosis of the human pancreatic cancer cell lines CAPAN-1 and BxPC-3, on the rat pancreatic cancer cell line AR42J, and on human fibroblasts as the control cell line. METHODS: Cellular viability and proliferation were determined using the LDH cytotoxicity and WST-1 assay, respectively. Apoptosis was detected by flow cytometric analyses of Annexin V-FITC labeled-cells, TUNEL assay and caspase activation. Student's t test or Mann-Whitney Rank Sum test were used to compare the data. RESULTS: Haelan concentrations lower than 8% showed no cytotoxic effects, whereas higher concentrations led to necrosis. Eight percent Haelan induced significant growth inhibition of CAPAN-1 and BxPC-3 cell lines by 30% and 35%, respectively, compared with the control. The proliferation rate of AR42J cells decreased by 50%, whereas the fibroblasts remained unaffected. An 1.1 fold increase in apoptosis was found in CAPAN-1 cells, whereas the number of apoptotic BxPC-3 cells was elevated 2-fold. The number of apoptotic AR42J cells and fibroblasts was elevated 1.5-fold, each. Inhibition of calpain activity amplified the Haelan-induced growth inhibition of CAPAN-1 and BxPC-3 cells, but failed to amplify the growth inhibition of Haelan-treated AR42J cells. In fibroblasts, calpain inhibition induced Haelan-independent growth inhibition. Calpain inhibition also amplified the Haelan-induced apoptotic activity in all cancer cell lines, but exerted no further effect in fibroblasts. CONCLUSIONS: The proliferation-inhibiting and apoptosis-inducing effects of Haelan are highly dependent on cell type and concentration administered. The results show for the first time that Haelan may be a promising candidate in the treatment of human pancreatic cancer, and its anticancer activity may be potentiated when administered with calpain inhibitors. PMID- 26138288 TI - Systematic screening of imaging biomarkers for the Islets of Langerhans, among clinically available positron emission tomography tracers. AB - INTRODUCTION: Functional imaging could be utilized for visualizing pancreatic islets of Langerhans. Therefore, we present a stepwise algorithm for screening of clinically available positron emission tomography (PET) tracers for their use in imaging of the neuroendocrine pancreas in the context of diabetes. METHODS: A stepwise procedure was developed for screening potential islet imaging agents. Suitable PET-tracer candidates were identified by their molecular mechanism of targeting. Clinical abdominal examinations were retrospectively analyzed for pancreatic uptake and retention. The target protein localization in the pancreas was assessed in silico by -omics approaches and the in vitro by binding assays to human pancreatic tissue. RESULTS: Six putative candidates were identified and screened by using the stepwise procedure. Among the tested PET tracers, only [(11)C]5-Hydroxy-tryptophan passed all steps. The remaining identified candidates were falsified as candidates and discarded following in silico and in vitro screening. CONCLUSIONS: Of the six clinically available PET tracers identified, [(11)C]5-HTP was found to be a promising candidate for beta cell imaging, based on intensity of in vivo pancreatic uptake in humans, and islet specificity as assessed on human pancreatic cell preparations. The flow scheme described herein constitutes a methodology for evaluating putative islet imaging biomarkers among clinically available PET tracers. PMID- 26138289 TI - High expectations: from treatment to prevention. PMID- 26138290 TI - Sequential vs. prolonged 14-day triple therapy for Helicobacter pylori eradication: the meta-analysis may be influenced by 'geographical weighting'. AB - BACKGROUND: Sequential therapy is a first-line regimen obtaining satisfactory Helicobacter pylori eradication. Triple therapy prolongation improves the success rate even if a recent meta-analysis showed satisfying results only for the 14-day regimen. Studies from Africa and North America were unavailable in previous meta analyses. AIM: To perform a meta-analysis comparing sequential vs. prolonged 14 day triple therapy with regard to 'geographic weighting' by considering subgroups analysis according to metronidazole/clarithromycin low and high resistance areas. METHODS: Based on PRISMA recommendations, we considered all first-line clinical studies from 2003 to November 2014. Randomised clinical trials (RCTs) were included by a search on PubMed, MEDLINE, Science Direct, EMBASE. Data on eradication rates were expressed as ITT. Risk ratio (RR), pooled RR and 95% confidence intervals were calculated by the Mantel-Haenszel method. Data were entered into RevMan 5.2 software (Nordic Cochrane Centre) using a random-effects model. RESULTS: Databases identified 194 studies; seven met the inclusion criteria. Overall results showed a similar effectiveness of the two regimens considered (RR = 0.99; 95% CI = 0.94-1.05; p = 0.75). In areas with high resistance to clarithromycin, sequential was superior to 14-day triple therapy (RR = 0.95; 95% CI = 0.90-1.00; p = 0.03). In areas with high metronidazole resistance, sequential and 14-day triple therapy were equivalent (RR = 0.99; 95% CI = 0.91-1.08; p = 0.82). CONCLUSIONS: 'Geographic weighting' could be the main factor affecting the lack of differences between sequential and 14-day triple therapy outcomes. PMID- 26138293 TI - Authors, editors and ethical ways of working. PMID- 26138292 TI - Role of Bcl-3 in the development of follicular helper T cells and in the pathogenesis of rheumatoid arthritis. AB - OBJECTIVE: We have previously shown that expression of the Bcl-3 gene, a member of the IkappaB family, is down-regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl-3 in the pathogenesis of RA. METHODS: DNA microarray analysis was used to compare the signal intensity of Bcl-3 in CD4+ T cells from untreated RA patients and healthy controls. We examined the roles of interleukin-6 (IL-6)/STAT-3 signaling in the induction of Bcl-3. In addition, we analyzed the gene expression profiles of Bcl-3-transduced CD4+ T cells by RNA sequencing. The effects of enforced expression as well as gene silencing of Bcl-3 on the development of follicular helper T (Tfh) cells were evaluated. Finally, we examined correlations between the signal intensities of Bcl-3 and Tfh cell related genes in CD4+ T cells from untreated RA patients. RESULTS: Bcl-3 levels were significantly higher in RA patients than in healthy controls. IL-6 induced Bcl-3 expression in CD4+ T cells in a STAT-3-dependent manner. Transcriptome analysis revealed that the expression of Bcl-6, a master regulator of Tfh cell differentiation, was significantly up-regulated by the enforced Bcl-3 expression. The enforced Bcl-3 expression increased, but Bcl-3 silencing decreased, the numbers of IL-21-producing Tfh-like cells. Bcl-3 levels in CD4+ T cells from RA patients correlated positively with the levels of Tfh cell-related genes CXCR5, inducible costimulator, and achaete-scute homolog 2. CONCLUSION: Bcl-3 is involved in the development of Tfh cells and the pathogenesis of RA, presumably by inducing IL-21 production. PMID- 26138294 TI - Human rights, health and our obligations to refugees. PMID- 26138295 TI - Citations for the Human Rights and Nursing Awards 2015. PMID- 26138299 TI - The Influence of Retrieval Practice Versus Delayed Judgments of Learning on Memory: Resolving a Memory-Metamemory Paradox. AB - The positive effect of delayed retrieval practice on subsequent test performance is robust; by contrast, making delayed judgments of learning (JOLs) encourages covert retrieval but has a minor influence on final test performance. In three experiments, we experimentally established and explored this memory-metamemory paradox. After initial study of paired associates (e.g., husky - ram), participants either were explicitly tested (husky - ?) or made a JOL. In Experiment 1, we adopted the standard JOL method, using a short retention interval, whereas in Experiments 2 and 3, we used a common testing-effect method involving a longer retention interval. Delayed JOLs did not boost test performance, but explicit delayed tests boosted memory after a longer retention interval. As important, participants spent less time to make JOLs than to retrieve responses. These data indicate that differences in the dynamics of retrieval for practice tests versus delayed JOLs are responsible for the paradox. PMID- 26138300 TI - Temporal Stability of Implicit Sequence Knowledge: Implications for Single-system Models of Memory. AB - Previous research has shown that explicit and implicit knowledge of artificial grammars may decay at different rates (e.g., Tamayo & Frensch, 2007; Tunney, 2003). We extend these findings to sequential regularities embedded in serial reaction time (SRT) tasks. We compared the forgetting patterns of implicit and explicit knowledge after a retention interval of 7 days without rehearsal. Explicit knowledge decayed after 7 days, whereas implicit knowledge was retained. These data were modeled according to the assumptions involved in the single system model suggested by Shanks, Wilkinson, and Channon (2003). The best fit for the model was obtained by modifying the parameters related to (a) the common knowledge-strength variable for implicit and explicit knowledge, and (b) reliability of the explicit test. We interpret these dissociations as a boundary condition for single-system models that assume constant random noise to explain dissociations in the forgetting patterns of implicit and explicit sequential knowledge. PMID- 26138301 TI - Stimulus-Response Bindings in the Go/NoGo Task: Effects on the Judged Typicality of Stimuli. AB - In the present paper, we explore the notion that judgments of typicality are dependent on the goal-relevancy of exemplars. However, we propose that relevancy can be derived from the response provided to stimulus, through the operation of stimulus-response bindings. Specifically, items associated with selection responses are tagged as "relevant" and will be subsequently judged as more typical of their categories, while stimuli associated with avoidance responses are tagged as "irrelevant" will be judged as less typical of their categories. We test this prediction with a Go-NoGo task with male and female faces. Results showed that (a) faces associated with a selection (Go) response were judged more typical of their gender category than faces associated with an avoidance (NoGo) response, and (b) these effects were more likely to be observed when the context is reactivated. Our results are consistent with the notion that representation of typicality is goal-oriented and contextually dependent. PMID- 26138291 TI - Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children. AB - Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood has an impact not only on renal clearance but also on absorption, distribution, metabolism and nonrenal clearance of drugs. 'Omics'-based technologies, such as proteomics and metabolomics, can be leveraged to uncover novel markers for kidney function during normal development, acute kidney injury, and chronic diseases. Pharmacometric modeling and simulation can be applied to simplify the design of pediatric investigations, characterize the effects of kidney function on drug exposure and response, and fine-tune dosing in pediatric patients, especially in those with impaired kidney function. One case study of amikacin dosing in neonates with reduced kidney function is presented. Collaborative efforts between clinicians and scientists in academia, industry, and regulatory agencies are required to evaluate new renal biomarkers, collect and share prospective pharmacokinetic, genetic and clinical data, build integrated pharmacometric models for key drugs, optimize and standardize dosing strategies, develop bedside decision tools, and enhance labels of drugs utilized in neonates, infants, and children. PMID- 26138302 TI - Biased Processing of Ambiguous Symptoms Favors the Initially Leading Hypothesis in Sequential Diagnostic Reasoning. AB - In sequential diagnostic reasoning, observed pieces of evidence activate hypotheses in memory and are integrated to reach a final diagnosis. The order of evidence can influence diagnostic reasoning. This article examines the processing of ambiguous evidence underlying order effects if multiple hypotheses are activated. In five experiments with a quasi-medical scenario, participants dealt with symptom sequences supporting multiple diagnoses. The symptom order, the response mode (end-of-sequence, step-by-step), and the consistency of evidence were manipulated. A primacy order effect occurred with both response modes suggesting that ambiguous pieces of evidence were distorted toward the hypothesis that strongly corresponded with the first piece. The primacy effect was partially counteracted by stepwise belief ratings, which strengthened the weight of recent evidence and promoted switching to an alternative diagnosis. We conclude that once hypotheses are generated, the interplay of coherence-oriented information distortion and memory-dependent analytic processes propagates into distinct order effects in diagnoses. PMID- 26138304 TI - Outcomes of referrals to Child Protective Services for medical neglect in patients with phenylketonuria: Experiences at a single treatment center. AB - Phenylketonuria (PKU) results in an accumulation of phenylalanine (phe) in the blood which can lead to multiple health consequences in affected individuals. Treatment for PKU is available; however adherence to medical management recommendations can be difficult. When recommendations are not followed and the health of a child is at risk, one intervention that may be necessary is a referral for medical neglect to the local child protective services (CPS) agency. This study summarizes the cases that were referred from our metabolic clinic at the Children's Hospital of Michigan to CPS, and the outcomes of that intervention. CPS referrals helped to improve adherence to medical management recommendations in the majority of cases, including a lower blood phe level for the child; however, at times that improvement did not occur until after a second referral and/or the child's temporary removal from the home. PMID- 26138305 TI - Serum levels of ET-1, M30, and angiopoietins-1 and -2 in HELLP syndrome and preeclampsia compared to controls. AB - PURPOSE: We aimed to compare the serum levels of ET-1, M30, and Angs-1 and -2 in patients with preeclampsia or HELLP syndrome, and normal controls. METHODS: In this cross-sectional study of 74 pregnant women, serum levels of ET-1, M30, and Angs-1 and -2 were measured in preeclamptic patients with or without HELLP syndrome. 74 pregnant women; 37 had healthy pregnancies, 25 had preeclampsia (PE), and 12 had HELLP syndrome. RESULTS: The age, body mass index, gravidity, and parity of patients with normal pregnancy, PE, and HELLP syndrome were comparable (p > 0.05). In HELLP syndrome, compared to healthy or preeclamptic pregnancies, platelet count was lower (p < 0.05) and the values of hepatic function tests were higher (p < 0.05). In HELLP syndrome, ET-1, M30, and Ang-2 were higher compared to healthy or preeclamptic pregnancies (p < 0.05); however, they increased in preeclamptic pregnancies compared to healthy pregnancies though not significant (p > 0.05). In PE or HELLP syndrome, Ang-1 was higher compared to a healthy pregnancy (p < 0.05); however, in HELLP syndrome, it was also higher than in PE though not significant (p > 0.05). We found no significant correlation among these biomarkers and hematological and biochemical parameters (p > 0.05). CONCLUSION: For the diagnosis of HELLP syndrome, increased levels of ET-1, M30, and Angs-1 and -2 appear as promising biomarkers after determination of their standardized threshold levels after further studies. As an apoptosis-related biomarker, serum M30 level has a merit to be the most promising test for prediction or differential diagnosis of HELLP syndrome in PE patients. PMID- 26138303 TI - INC280, an orally available small molecule inhibitor of c-MET, reduces migration and adhesion in ovarian cancer cell models. AB - 5-year survival rates for ovarian cancer are approximately 40%, and for women diagnosed at late stage (the majority), just 27%. This indicates a dire need for new treatments to improve survival rates. Recent molecular characterization has greatly improved our understanding of the disease and allowed the identification of potential new targets. One such pathway of interest is the HGF/c-MET axis. Activation of the HGF/c-MET axis has been demonstrated in certain ovarian tumours, and been found to be associated with decreased overall survival, suggesting its potential as a therapeutic target. The objective of this study was to determine the efficacy of a novel, highly potent, orally-bioavailable c-MET inhibitor, INC280, in blocking cell phenotypes important in ovarian cancer metastasis. Using in vitro and ex vivo models, we demonstrate that INC280 inhibits HGF-induced c-MET, and reduces downstream signalling. HGF-stimulated chemotactic and random migration are decreased by INC280 treatment, to levels seen in non-stimulated cells. Additionally, HGF-induced adhesion of cancer cells to peritoneal tissue is significantly decreased by INC280 treatment. Overall, these data indicate that INC280 inhibits many cell behaviours that promote ovarian cancer metastasis, and merits further investigation as a therapeutic candidate in the treatment of patients with ovarian cancer. PMID- 26138306 TI - Association of endometriosis and breast cancer: mini review of the literature. AB - BACKGROUND: Endometriosis is a common, estrogen-dependent, gynecological disease, which is defined as the presence of endometrial tissue outside the uterine cavity. Current data have associated endometriosis with specific malignancies, including ovarian and breast cancer. PURPOSE: The purpose of our study is to summarize and present published literature providing evidence regarding the possible relationship between endometriosis and breast cancer. METHODS: Pubmed and Scopus databases were searched systematically for studies that sought to identify a potential association of endometriosis and breast cancer. 15 relevant articles were retrieved and included in the present review. RESULTS: A small number of observational studies have shown a correlation of endometriosis and breast cancer. Other studies found that the risk of breast cancer increases with age. The scenario of an early interruption of the inflammatory process, derived from endometriosis, by oophorectomy and a possible consequent decrease in the risk of breast cancer has also been proposed. The hypothesis that both conditions could be related through common mutations on BRAC1 and BRAC2 genes has also been investigated. CONCLUSION: The available published evidence is inconclusive. Further studies are needed to evaluate the association of endometriosis and breast cancer and the possible pathogenetic pathways that relate the two disorders. PMID- 26138307 TI - Green tea, black tea consumption and risk of endometrial cancer: a systematic review and meta-analysis. AB - BACKGROUND: Several studies have assessed the association between green and black tea consumption and the risk of endometrial cancer (EC) and have yielded inconsistent results. OBJECTIVE: The purpose of this meta-analysis is to systematically analyze the effect of green tea and black tea on EC risk. METHODS: PubMed, Embase, Cochrane Library and China Biological Medicine Database were searched through February 2, 2015 to identify studies that met pre-stated inclusion criteria. Overall relative risk (RR) was estimated based on the highest and lowest levels of green/black tea consumption. Dose-response relationships were evaluated with the data from categories of green/black tea intake in each study. RESULTS: For green tea, the summary RR indicated that the highest green tea consumption was associated with a reduced risk of EC (RR 0.78, 95 % CI 0.66 0.92). Furthermore, an increase in green tea consumption of one cup per day was associated with an 11 % decreased risk of developing EC. (RR 0.89, 95 % CI 0.84 0.94). For black tea, no statistically significant association was observed in the meta-analysis (highest versus non/lowest, RR 0.99, 95 % CI 0.79-1.23; increment of one cup/day, RR 0.99, 95 % CI 0.94-1.03). The power of the estimate of green tea and black tea with risk of EC was 84.33 and 5.07 %, respectively. The quality of evidence for the association between green and black tea with EC risk was moderate and very low, respectively. CONCLUSIONS: The results from this meta-analysis indicate that green tea, but not black tea, may be related to a reduction of EC risk. Large population-based randomized controlled trials and large prospective cohort studies are required to obtain a definitive conclusion and determine the mechanisms underlying this association. PMID- 26138308 TI - Improving efficiency of a regional stand alone bone bank. AB - The introduction of a stand-alone Bone Bank in our Regional Orthopaedic Hospital has improved the availability of femoral head allograft. Benninger et al. (Bone Joint J 96-B:1307-1311, 2014), demonstrated their institutions bank to be cost effective despite a 30 % discard rate for harvested allograft. We sought to audit our own discard rates and subsequent cost-effectiveness of our bone bank. Donor recruitment. Before approaching a potential donor, our establishment's nurse specialists review their clinical notes and biochemical laboratory results, available on a regional Electronic Care Records. They view femoral head architecture on radiographs against set criteria, Patient Archive and Communication system (SECTRA, Sweden). In total 1383 femoral heads were harvested, 247 were discarded giving an overall rate of 17.9 %. The most common reasons for discard of harvested graft was a positive microbiology/bacteriology result, n = 96 (38.9 %). After a rise in discard rates in 2007, we have steadily reduced our discard rates since 2006/2007 (28.2 %), 2008/2009 (17 %), 2010/2011 (14.8 %), and finally to 10.3 % in 2012/2013. In the current financial year, our cost to harvest, test, store and release a femoral head is L 610. With a structured donor recruitment process and unique pre-operative radiographic analysis we have successfully reduced our discard rates bi-annually making our bone bank increasingly cost-effective. PMID- 26138309 TI - 3D bio-etching of a complex composite-like embryonic tissue. AB - Morphogenesis involves a complex series of cell signaling, migration and differentiation events that are coordinated as tissues self-assemble during embryonic development. Collective cell movements such as those that occur during morphogenesis have typically been studied in 2D with single layers of cultured cells adhering to rigid substrates such as glass or plastic. In vivo, the intricacies of the 3D microenvironment and complex 3D responses are pivotal in the formation of functional tissues. To study such processes as collective cell movements within 3D multilayered tissues, we developed a microfluidic technique capable of producing complex 3D laminar multicellular structures. We call this technique "3D tissue-etching" because it is analogous to techniques used in the microelectromechanics (MEMS) field where complex 3D structures are built by successively removing material from a monolithic solid through subtractive manufacturing. We use a custom-designed microfluidic control system to deliver a range of tissue etching reagents (detergents, chelators, proteases, etc.) to specific regions of multilayered tissues. These tissues were previously isolated by microsurgical excision from embryos of the African claw-toed frog, Xenopus laevis. The ability to shape the 3D form of multicellular tissues and to control 3D stimulation will have a high impact on tissue engineering and regeneration applications in bioengineering and medicine as well as provide significant improvements in the synthesis of highly complex 3D integrated multicellular biosystems. PMID- 26138310 TI - Acoustothermal heating of polydimethylsiloxane microfluidic system. AB - We report an observation of rapid (exceeding 2,000 K/s) heating of polydimethylsiloxane (PDMS), one of the most popular microchannel materials, under cyclic loadings at high (~MHz) frequencies. A microheater was developed based on the finding. The heating mechanism utilized vibration damping in PDMS induced by sound waves that were generated and precisely controlled using a conventional surface acoustic wave (SAW) microfluidic system. The refraction of SAW into the PDMS microchip, called the leaky SAW, takes a form of bulk wave and rapidly heats the microchannels in a volumetric manner. The penetration depths were measured to range from 210 MUm to 1290 MUm, enough to cover most sizes of microchannels. The energy conversion efficiency was SAW frequency-dependent and measured to be the highest at around 30 MHz. Independent actuation of each interdigital transducer (IDT) enabled independent manipulation of SAWs, permitting spatiotemporal control of temperature on the microchip. All the advantages of this microheater facilitated a two-step continuous flow polymerase chain reaction (CFPCR) to achieve the billion-fold amplification of a 134 bp DNA amplicon in less than 3 min. PMID- 26138311 TI - Investigation on Transient Oscillation of Droplet Deformation before Conical Breakup under Alternating Current Electric Field. AB - In this paper, the conical breakup of a water droplet suspended in oil under the alternating current (ac) electric field was experimentally studied with the help of a high-speed video camera. We observed three stages of transient oscillation of deformation characterized by deformation degree l* before the conical breakup that were described in detail. Then a theoretical model was developed to find out the dynamic mechanisms of that behavior. Despite a very small discrepancy, good agreement between model predictions and experimental observations of the evolution of the droplet deformation was observed, and the possible reasons for the discrepancy were discussed as well. Finally, the stresses on the interface were calculated with the theoretical model and their influence on the dynamic behavior before the breakup was obtained. The differences between the droplet breakup mode of ac and direct current electric field are also discussed in our paper. PMID- 26138312 TI - Particle retention by respiratory epithelial cells is associated with persistent biological effect. AB - The biological effect of particles on respiratory epithelial cells involves, in part, the generation of an oxidative stress and a consequent cascade of reactions culminating in inflammatory mediator release. Whether there is either an immediate, transitory activation or a persistent response of the cells to the particles has not been established. We tested the postulate that respiratory epithelial cells exposed to wood smoke particle (WSP) would demonstrate increased oxidative stress and mediator release following re-seeding and propagation of the cells for two generations post-initial exposure. BEAS-2B cells grown to confluence (G0) in 75 cm(2) flasks were treated for 18 h with the WSP at 0, 25, 50 and 100 ug/ml. The flasks were then used to seed another set of flasks as well as 12- and 96-well plates (G1). These flasks were similarly grown to confluence and the process repeated (G2). Cell viability was assayed using trypan blue dye exclusion and was >85%. Dichlorohydrofluorescein fluorescence after exposure of BEAS-2B cells to 50 and 100 ug/ml WSP increased in all three generations when expressed as a ratio to unexposed cells. Similarly, IL-6 and IL-8 release following the initial exposure of cells to 100 ug/ml WSP increased in all three generations when expressed as a ratio to unexposed cells. The persistence of oxidative stress and inflammatory mediator release for two generations of cells beyond the initial exposure supports a postulate of continued cell response to retained particle. PMID- 26138313 TI - Characterization of biochemical, functional and structural changes in mice respiratory organs chronically exposed to cigarette smoke. AB - Female C57BL/6 mice were exposed to mainstream cigarette smoke at 600 MUg WTPM/L, 4 h/day and 5 days/week for up to 52 weeks. At 26, 52 and 65 weeks (52 weeks of exposure plus 13 weeks of no exposure), lungs were assessed for inflammation, function, histopathology and morphometry. Structural changes were observed and accompanied by altered lung function at 26 and 52 weeks (e.g. increase of static compliance and hysteresis, and decrease of elastance). Lung morphometry quantified significant increase in airspace enlargement at 52 weeks. Chronic smoke exposure induced inflammation in respiratory organs, e.g. mixed inflammatory cell infiltrates, perivascular lymphocyte infiltrates and pigmented alveolar macrophages in the lungs. Minimal or mild alveolar emphysema was diagnosed in 70% by 26 weeks or 80% by 52 weeks. After 13 weeks of recovery, most biochemical, histopathological and morphometrical alterations were restored, while emphysema was observed to persist at 18% incidence by 65 weeks. In conclusion, the employed exposure conditions induced emphysematous changes in the lungs, accompanied by altered lung function and morphological/histopathological changes. Following the 13 weeks of no exposure, morphological changes persisted, although some functional/biochemical alterations regressed. PMID- 26138314 TI - High Peritoneal Glucose Exposure Is Associated with Increased Incidence of Relapsing and Recurrent Bacterial Peritonitis in Patients Undergoing Peritoneal Dialysis. AB - AIM: We investigated the association of peritoneal glucose exposure and dialysis exchange number with peritonitis outcome in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: The first episodes of bacterial peritonitis were retrospectively analyzed in 187 CAPD patients. Peritoneal glucose exposure was calculated based on PD prescription at the onset of peritonitis. RESULTS: Patients with peritoneal glucose exposure <=140 g/day showed a higher and complete cure rate of peritonitis (66 vs. 51.7%, p = 0.047), lower occurrence of relapsing/recurrent peritonitis (10.0 vs. 21.8%, p = 0.026) and catheter removal (14.0 vs. 26.4%, p = 0.033). Patients who exchanged more than three times every day demonstrated marginally higher catheter removal rate (24.1 vs. 13.0%, p = 0.085). Logistic analysis indicated that peritoneal glucose exposure >140 g/day was an independent predictor for relapsing/recurrent peritonitis (RR: 1.959, p = 0.042). CONCLUSION: High peritoneal glucose exposure is associated with increased incidence of relapsing/recurrent peritonitis in CAPD patients. PMID- 26138315 TI - Microwave-assisted solution-liquid-solid growth of Ge1-xSnx nanowires with high tin content. AB - A microwave assisted growth procedure for the first bottom-up synthesis of germanium tin alloy (Ge1-xSnx) nanowires with constant diameter along their axis was developed. Ge1-xSnx nanowires with mean diameters of 190 +/- 30 nm and a homogeneous distribution of 12.4 +/- 0.7% Sn in Ge have been synthesized. PMID- 26138316 TI - Phototherapy on the Treatment of Burning Mouth Syndrome: A Prospective Analysis of 20 Cases. AB - The aim of this study was to report the effect of laser phototherapy (LPT) on the treatment of burning mouth syndrome (BMS). This prospective clinical study reports on preliminary outcomes of twenty volunteers diagnosed with BMS who have undergone the conventional treatment prior to laser phototherapy. LPT consisted of weekly sessions of LPT (660 nm), for a period of 10 weeks. The laser protocol consisted of the following parameters: 40 mW, 10 J cm(2) and 0.4 J per point, irradiation time of 10 s. In all sessions, the burning intensity was evaluated with a 10 cm Visual Analogue Scale (VAS). The burning intensity evaluation by VAS was performed immediately before and after each LPT session. Nonparametric test of Wilcoxon was used for statistical analysis, considering a significance level of 5%. All volunteers reported reduced burning intensity in all sessions when compared to the previous one and reduction in VAS scores by up to 49% in the last clinical session when compared to the first session. When only the VAS baseline of the first session was compared with the consecutive sessions, there was a statistically significant reduction in VAS scores in almost all sessions. The LPT may be an alternative treatment for the relief of oral burning symptoms in patients with BMS. PMID- 26138317 TI - The Environmental Cost of Protein Food Choices--CORRIGENDUM. PMID- 26138318 TI - Urocortin attenuates TGFbeta1-induced Snail1 and slug expressions: inhibitory role of Smad7 in Smad2/3 signaling in breast cancer cells. AB - Corticortropin-releasing hormone (CRH) family are multifunctional endocrine factors that regulate proliferation, apoptosis, and migration of various types of cancer cells. Deregulation of the transforming growth factor beta1(TGFbeta1) signal transduction promotes aggressive metastatic properties in late-stage breast cancers. We previously have demonstrated in breast cancer cell line that CRH suppressed TGFbeta1-induced Epithelial-Mesenchymal Transition (EMT) via induction of E-cadherin. Our present data in MCF-7 and MDA-MB-231 cells showed that Urocortin (Ucn, a member of CRH family) inhibited TGFbeta1 signaling by reducing Smad2/3 activation and subsequent nuclear translocation through increasing Smad7 expression, leading to downregulation of Snail1 and Slug, the two EMT promoters. We further found that Antalarmin (CRH receptor type 1, CRHR1 antagonist) and Antisauvagine-30 (CRH receptor type2, CRHR2 antagonist) abrogated the effects of Ucn on TGFbeta1 signaling, implying that both active CRHR1 and CRHR2 participate in Ucn-repressed TGFbeta1 signaling. Our findings, for the fist time, identify Ucn as a potential mediator that inhibits oncogenic signaling by TGFbeta1 and suggest that activating CRHR1 and R2 may prove effective in diminishing breast cancer progression stimulated by TGFbeta1. PMID- 26138319 TI - Three blocks are not enough--Blocking of the murine IgG receptor FcgammaRIV is crucial for proper characterization of cells by FACS analysis. PMID- 26138320 TI - Automatic In-Syringe Dispersive Microsolid Phase Extraction Using Magnetic Metal Organic Frameworks. AB - A novel automatic strategy for the use of micro- and nanomaterials as sorbents for dispersive microsolid phase extraction (D-MU-SPE) based on the lab-in-syringe concept is reported. Using the developed technique, the implementation of magnetic metal-organic framework (MOF) materials for automatic solid-phase extraction has been achieved for the first time. A hybrid material based on submicrometric MOF crystals containing Fe3O4 nanoparticles was prepared and retained in the surface of a miniature magnetic bar. The magnetic bar was placed inside the syringe of an automatic bidirectional syringe pump, enabling dispersion and subsequent magnetic retrieval of the MOF hybrid material by automatic activation/deactivation of magnetic stirring. Using malachite green (MG) as a model adsorption analyte, a limit of detection of 0.012 mg/L and a linear working range of 0.04-2 mg/L were obtained for a sample volume equal to the syringe volume (5 mL). MG preconcentration was linear up to a volume of 40 mL, obtaining an enrichment factor of 120. The analysis throughput is 18 h(-1), and up to 3000 extractions/g of material can be performed. Recoveries ranging between 95 and 107% were obtained for the analysis of MG in different types of water and trout fish samples. The developed automatic D-MU-SPE technique is a safe alternative for the use of small-sized materials for sample preparation and is readily implementable to other magnetic materials independent of their size and shape and can be easily hyphenated to the majority of detectors and separation techniques. PMID- 26138321 TI - Afraid of Delivering at the Hospital or Afraid of Delivering at Home: A Qualitative Study of Thai Hmong Families' Decision-Making About Maternity Services. AB - Thailand has high rates of maternity services; both antenatal care (ANC) and hospital delivery are widely used by its citizens. A recent Northern Thailand survey showed that Hmong women used maternity services at lower rates. Our objectives were to identify Hmong families' socio-cultural reasons for using and not using maternity services, and suggest ways to improve Hmong women's use of maternity services. In one Hmong village, we classified all 98 pregnancies in the previous 5 years into four categories: no ANC/home birth, ANC/home, no ANC/hospital, ANC/hospital. We conducted life-history case studies of 4 women from each category plus their 12 husbands, and 17 elders. We used grounded theory to guide qualitative analysis. Families not using maternity services considered pregnancy a normal process that only needed traditional home support. In addition, they disliked institutional processes that interfered with cultural birth practices, distrusted discriminatory personnel, and detested invasive, involuntary hospital procedures. Families using services perceived physical needs or potential delivery risks that could benefit from obstetrical assistance not available at home. While they disliked aspects of hospital births, they tolerated these conditions for access to obstetrical care they might need. Families also considered cost, travel distance, and time as structural issues. The families ultimately balanced their fear of delivering at home with their fear of delivering at the hospital. Providing health education about pregnancy risks, and changing healthcare practices to accommodate Hmong people's desires for culturally-appropriate family-centered care, which are consistent with evidence based obstetrics, might improve Hmong women's use of maternity services. PMID- 26138322 TI - A Longitudinal Study of Changes in Prenatal Care Utilization Between First and Second Births and Low Birth Weight. AB - OBJECTIVES: Because previous analyses of prenatal care (PNC) utilization and risk of low birth weight (LBW) may have been influenced by selection bias, we conducted a study using longitudinal data of women with repeat pregnancies. METHODS: We analyzed Washington State birth certificates of first and second live births (2003-2012). We estimated relative risk (RR) of LBW at second birth associated with Kotelchuck Index PNC level among women stratified by level of PNC in their first birth (n = 67,571). RESULTS: Among women with inadequate PNC prior to their first birth (n = 10,355), women with intermediate or adequate PNC before their second birth (n = 7464) had a reduced risk of LBW (adjusted RR 0.61, 95% CI: 0.48, 0.78) compared to those whose PNC level remained inadequate. Likewise, among women with intermediate or adequate PNC prior to their first birth (n = 57,216), those with inadequate PNC before the second birth (n = 7095) had higher risk of LBW (adjusted RR 1.59, 95% CI: 1.36, 1.85) compared to those who remained at intermediate or adequate PNC. CONCLUSIONS: Our findings support the hypothesis that PNC decreases LBW risk at second birth, independent of factors related to the utilization of PNC at first birth. PMID- 26138323 TI - Use of an Electron Beam Melting Manufactured Titanium Collared Cementless Femoral Stem to Resist Subsidence After Canine Total Hip Replacement. AB - OBJECTIVES: To evaluate the effect of a collared electron beam melting (EBM) manufactured titanium cementless femoral stem on implant subsidence after total hip replacement (THR). STUDY DESIGN: Prospective study ANIMALS: Dogs (n = 26); 33 THR. METHODS: Records were maintained on the first 110 consecutive THR using an EBM collared femoral stem. Radiographs on the first 33 THR that had 6-months follow-up were evaluated for implant subsidence. These results were compared to 27 dogs with subsidence after THR with a Co Cr collarless stem. RESULTS: Dogs that had EBM collared stem THR had a mean body weight of 35.4 kg, body condition score (BCS) of 6.21, and mean canal flare index (CFI) of 1.56. EBM stem sizes used (number implanted) were #7 (13), #8 (10), #9 (8), and #10 (2). Subsidence of collared stems did not occur if the collar was in contact with cortical bone during surgery. Subsidence of 1-3 mm occurred closing a gap between the collar and bone if contact was not made during surgery, but subsidence stopped once contact was made. No major complications directly related to the EBM collared stem were encountered. CONCLUSIONS: A collar on a cementless femoral stem in contact with cortical bone resists subsidence. PMID- 26138324 TI - [I10W]tigerinin-1R enhances both insulin sensitivity and pancreatic beta cell function and decreases adiposity and plasma triglycerides in high-fat mice. AB - AIMS: We have previously described the insulinotropic activities of [I10W]tigerinin-1R (RVCSAIPLPWCH.NH2) in vitro. In this study, we investigated the effects of the peptide on nutrient homoeostasis in mice with diet-induced obesity and insulin resistance. METHODS: Male NIH Swiss mice were maintained on a high-fat diet for 12 weeks prior to the study. Twice-daily intraperitoneal injections of [I10W]tigerinin-1R (75 nmol/kg body weight) were administered for 28 days. Body weight, energy intake, body fat content, and plasma concentrations of triglyceride, cholesterol, non-fasting glucose and insulin were monitored. Effects of the peptide on glycaemic control were measured by glucose tolerance and insulin sensitivity tests. Pancreatic hormone content and insulin secretory responses of islets isolated from treated and untreated mice were examined. Immunohistochemical analysis was performed to study possible changes in islet morphology. RESULTS: Administration of [I10W]tigerinin-1R to high-fat-fed mice produced significant (P < 0.05) decreases in plasma glucose, glucagon and triglyceride concentrations and an increase in plasma insulin compared to high fat-fed controls. No changes in body weight or energy intake were observed with peptide treatment, but glycaemic control was significantly improved in response to oral or intraperitoneal glucose. Insulin sensitivity and secretory responses of islets to established insulin secretagogues were also significantly improved in peptide-treated mice. Total body fat, pancreatic insulin and glucagon contents, islet, beta and alpha cell areas were all significantly decreased in treated mice. CONCLUSIONS: This study shows that [I10W]tigerinin-1R improves insulin sensitivity, islet function and glycaemic control in high-fat-fed mice and has potential as a template for development of novel anti-diabetic agents. PMID- 26138325 TI - Oligoethylene glycol-substituted aza-BODIPY dyes as red emitting ER-probes. AB - This study features aza-BODIPY (BF2-chelated azadipyrromethene) dyes with two aromatic substituents linked by oligoethylene glycol fragments to increase hydrophilicity of aza-BODIPY for applications in intracellular imaging. To prepare these, two chalcones were attached alpha,omega onto oligoethylene glycol fragments, then reacted with nitromethane anion. Conjugate addition products from this reaction were then subjected to typical conditions for synthesis of aza BODIPY dyes (NH4OAc, (n)BuOH, 120 degrees C); formation of boracycles in this reaction was concomitant with creation of macrocycles containing the oligoethylene glycol fragments. Similar dyes with acyclic oligoelythene glycol substituents in the same position were used to compare the efficiencies of the intra- and inter-molecular aza-BODIPY forming reactions, and the characteristics of the products. All the fluors with oligoethylene glycol fragments, i.e. cyclic or acyclic, localized in the endoplasmic reticulum of a fibroblast cell line (WEHI-13VAR), the human pancreatic cancer cell line (PANC-1, rough ER predominates) and human liver cancer cell line (HepG2, smooth ER prevalent). These fluors are potentially useful for near IR (lambdamax emis at 730 nm) ER staining probes. PMID- 26138326 TI - Reply: To PMID 25495209. PMID- 26138327 TI - A square-shaped wrist as a predictor of carpal tunnel syndrome: A meta-analysis. AB - INTRODUCTION: This meta-analysis aims to assess an association between wrist ratio (wrist thickness/wrist width) and carpal tunnel syndrome (CTS). METHODS: Sixteen studies qualified for a random-effects meta-analysis. RESULTS: Mean wrist ratio was higher in individuals with CTS compared with those without CTS [pooled mean difference 0.036, 95% confidence interval (CI) 0.025-0.046]. Pooled odds ratio (OR) of CTS for mean wrist ratio was 4.56 (95% CI 2.97-6.99), and for wrist ratio >=0.70 vs. <0.70 it was 2.73 (95% CI 1.49-5.01). In addition, the pooled OR for a 1-unit (0.01) increase in wrist ratio was 1.12 (CI 1.09-1.16). The association between wrist ratio and CTS did not differ between men and women. Moreover, there was no evidence of publication bias. CONCLUSIONS: This meta analysis suggests that a square-shaped wrist is a predictor for CTS in both men and women. Future studies should explore whether a square-shaped wrist can potentiate the adverse effects of obesity and occupational workloads on CTS. PMID- 26138328 TI - The Phytotherapeutic Fenugreek as Trigger of Toxic Epidermal Necrolysis. AB - We describe the case of a 32-year-old woman who presented to the hospital with generalized painful exanthema, blisters and erosions 1 month after giving birth to a healthy girl. The patient's medical history was inconspicuous for comorbidities; however, it included the incidental intake of pain killers and a herbal preparation (fenugreek), which she took regularly over the last 4 weeks to improve lactation. Based on the clinical characteristics, we suspected toxic epidermal necrolysis (TEN), a severe cutaneous adverse drug reaction, which was confirmed by skin biopsy. The patient was treated with high-dose intravenous human immunoglobulins and was discharged 2 weeks after hospital admission in good condition. The allergological workup identified fenugreek as the most likely causative agent. Given the increased self-medication of freely available phytotherapeutics by patients in industrialized countries, herbal mixtures should be taken into consideration in the diagnostic workup of TEN. PMID- 26138329 TI - Reconsidering contact precautions for endemic methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. AB - BACKGROUND: Whether contact precautions (CP) are required to control the endemic transmission of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin resistant Enterococcus (VRE) in acute care hospitals is controversial in light of improvements in hand hygiene, MRSA decolonization, environmental cleaning and disinfection, fomite elimination, and chlorhexidine bathing. OBJECTIVE: To provide a framework for decision making around use of CP for endemic MRSA and VRE based on a summary of evidence related to use of CP, including impact on patients and patient care processes, and current practices in use of CP for MRSA and VRE in US hospitals. DESIGN: A literature review, a survey of Society for Healthcare Epidemiology of America Research Network members on use of CP, and a detailed examination of the experience of a convenience sample of hospitals not using CP for MRSA or VRE. PARTICIPANTS: Hospital epidemiologists and infection prevention experts. RESULTS: No high quality data support or reject use of CP for endemic MRSA or VRE. Our survey found more than 90% of responding hospitals currently use CP for MRSA and VRE, but approximately 60% are interested in using CP in a different manner. More than 30 US hospitals do not use CP for control of endemic MRSA or VRE. CONCLUSIONS: Higher quality research on the benefits and harms of CP in the control of endemic MRSA and VRE is needed. Until more definitive data are available, the use of CP for endemic MRSA or VRE in acute care hospitals should be guided by local needs and resources. PMID- 26138330 TI - Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal micron Liuhe Pill ointment in rats. AB - OBJECTIVE: To explore the effect of acute pancreatitis (AP) on the pharmacokinetics of herbal ointment micron Liuhe Pill, MLHP) components in anesthetized rats. METHODS: Rats were randomly divided into a AP model group (n=6) and a normal group as a control (n=6). The rat model of AP was induced by intraperitoneal injection of L-arginine in rats (15 mg/kg, twice, interval 1 h). Chinese herbal ointment MLHP was used externally on the belly after the 2nd injection for 48 h in both groups. Emodin, rhein, aloe emodin, physcion, chrysophanol from MLHP were detected and quantified in rat serum and pancreas (at 48 h) by high performance liquid chromatography-tandem mass spectrometry. RESULTS: Among the five components, only emodin, aloe emodin and physcion from MLHP were detected in all rat serum and most of the rats' pancreas. Rhein and chrysophanol were not detected in both serum and pancreas. T1/2alpha of emodin and physcion in MLHP were obviously shorter in the AP model group than those in the normal group (P<0.05), while there was no difference for T1/2alpha of aloe emodin. The peak concentration and area under curve of all three components were much higher in the AP group than those in the normal group with MLHP in external application for 48 h (P<0.05). Furthermore, the mean residence time (MRT) and maximum plasma concentration (Tmax) of emodin and aloe emodin were obviously longer in the AP model group than those in the normal control group (P<0.05). There was no significant difference for Ka of all components between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in the AP model group than in the normal group (0.61+/-0.54 ng/mL, 0.42+/-0.37 ng/mL, respectively,P<0.05). Aloe emodin could be detected in all rats' pancreas at 48 h in both groups and their mean pancreatic concentration were similar (0.31+/-0.24 ng/mL, 0.33+/-0.17 ng/mL, respectively,P>0.05). Physcion could be detected in pancreas of most rats in the AP model while only two rats in the normal group. CONCLUSION: AP could significantly affect the pharmacokinetics of absorbed components of Chinese herbal MLHP ointment in rats. PMID- 26138331 TI - Food neophiles: Profiling the adventurous eater. AB - OBJECTIVE: The study objective was to identify how food neophilia-having an adventurous eating style for new/different foods-may relate to body mass index (BMI). METHODS: A nationwide online survey was conducted in 2012 with a group of 501 diverse young women (mean age = 26.8, mean BMI = 25.96). Items measured eating adventurousness, perceptions of novel foods, lifestyle and psychological characteristics, and BMI (dependent variable). RESULTS: Linear regressions were run to examine associations between eating adventurousness and weight-related outcomes. To examine mean differences between adventurous and non-adventurous eaters, a one-way ANOVA was run for variables on perceptions of novel foods, lifestyle, and psychology (significance level = P < 0.05). Food neophiles had lower BMIs (P < 0.01) and were more likely to cook to connect with their heritage, host friends for dinner, be physically active, and be concerned about the healthfulness of food, when compared to non-adventurous eaters (all P values < 0.05). CONCLUSIONS: Promoting adventurous eating in adults could help individuals lose/maintain weight without feeling as restricted. Given the lack of research on food neophiles, future studies should examine their characteristics and behaviors, as well as how food neophiles may intersect with others interested in food (e.g., foodies). PMID- 26138332 TI - Routine weighing of women during pregnancy-is it time to change current practice? PMID- 26138333 TI - PACAP Modulates Acetylcholine-Elicited Contractions at Nicotinic Neuromuscular Contacts of the Land Snail. AB - In this study, we investigate the potentiating effect of PACAP27 on cholinergic neuromuscular transmission in the recently discovered flexor muscles of the land snail, Helix pomatia. Using immunohistochemistry, we show that PACAP and PAC1 receptors are present in nerve fibers innervating the flexor muscles but not in the muscle itself. We also observed that PACAP27 exerts both pre- and postsynaptic effects on the cholinergic synapse and performed tests using a broad spectrum of chemicals in order to explore the possible intracellular pathways through which PACAP mediates its stimulatory effect. Our pharmacological data demonstrate that PACAP27 presynaptically enhances the release of acetylcholine by activating the adenylate cyclase-cAMP-PKA pathway. Postsynaptically, PACAP27 was found to enhance muscle contractility by PKC-mediated signaling pathway resulting in an increased Ca(2+) release from intracellular stores. These findings suggest that regulation of Ca(2+) release may contribute to the stimulatory effect of PACAP. Our data are the first demonstration of the potentiating effect of PACAP27 at the molluscan excitatory neuromuscular contact. PMID- 26138334 TI - Islet autoantibody phenotypes and incidence in children at increased risk for type 1 diabetes. AB - AIMS/HYPOTHESIS: Autoantibodies that precede type 1 diabetes frequently develop in early childhood and target distinct beta cell proteins. The aim of this study was to determine the heterogeneity of islet autoantibody development and fate. METHODS: The ages of development of insulin autoantibodies (IAA) and GAD autoantibodies (GADA), followed by multiple islet autoantibodies and progression to diabetes were examined in 2,441 children participating in two German birth cohorts. RESULTS: In 218 children who developed islet autoantibodies, the first islet autoantibody-positive sample was characterised by single IAA in 80 (37%), multiple islet autoantibodies in 68 (31%) and single GADA in 63 (29%) children. Of the children who were single antibody positive at seroconversion, 35 (44%) IAA positive and 15 (24%) GADA-positive children developed multiple islet autoantibodies. Single persistent antibodies had heterogeneous affinities; GADA were also heterogeneous in their binding to N-terminally truncated GAD65 and in an ELISA. Progression to diabetes occurred in >50% of children within 10 years in all groups that developed multiple islet autoantibodies and in 44% of children with persistent single high-affinity IAA or persistent single GADA that were positive in both a radiobinding assay and ELISA. The earliest autoantibody development was seen in children with single IAA that progressed to multiple islet autoantibodies or in those with persistent high-affinity single IAA, with a sharp peak in incidence observed at age 9 months. The peak incidence occurred at age 2 years for children who underwent seroconversion directly to multiple islet autoantibodies and at 5 years for children who first seroconverted to GADA and subsequently developed other autoantibodies. Seroconversion to low-affinity IAA or persistent single GADA occurred at a low incidence after the age of 9 months. CONCLUSIONS/INTERPRETATION: Children of different ages have differing susceptibilities to autoimmunisation against specific beta cell autoantigens. PMID- 26138337 TI - The Past, Current, and Future. PMID- 26138335 TI - CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1 Deficient Ovarian Cancer. AB - Immune checkpoint blockade has shown significant therapeutic efficacy in melanoma and other solid tumors, but results in ovarian cancer have been limited. With evidence that tumor immunogenicity modulates the response to checkpoint blockade, and data indicating that BRCA-deficient ovarian cancers express higher levels of immune response genes, we hypothesized that BRCA(-) ovarian tumors would be vulnerable to checkpoint blockade. To test this hypothesis, we used an immunocompetent BRCA1-deficient murine ovarian cancer model to compare treatment with CTLA-4 or PD-1/PD-L1 antibodies alone or combined with targeted cytotoxic therapy using a PARP inhibitor. Correlative studies were performed in vitro using human BRCA1(-) cells. We found that CTLA-4 antibody, but not PD-1/PD-L1 blockade, synergized therapeutically with the PARP inhibitor, resulting in immune-mediated tumor clearance and long-term survival in a majority of animals (P < 0.0001). The survival benefit of this combination was T-cell mediated and dependent on increases in local IFNgamma production in the peritoneal tumor environment. Evidence of protective immune memory was observed more than 60 days after completion of therapy. Similar increases in the cytotoxic effect of PARP inhibition in the presence of elevated levels of IFNgamma in human BRCA1(-) cancer cells support the translational potential of this treatment protocol. These results demonstrate that CTLA-4 blockade combined with PARP inhibition induces protective antitumor immunity and significant survival benefit in the BRCA1(-) tumor model, and support clinical testing of this regimen to improve outcomes for women with hereditary ovarian cancer. PMID- 26138336 TI - FTY720 inhibited proinflammatory cytokine release and osteoclastogenesis induced by Aggregatibacter actinomycetemcomitans. AB - BACKGROUND: Periodontitis is a bacteria-driven inflammatory bone loss disease. Previous studies showed that the oral pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) stimulated the generation of sphingosine 1 phosphate (S1P). In addition, S1P signaling regulated the migration of osteoclast precursors and affected osteoclastogenesis. Furthermore, treatment with FTY720 (also called fingolimod, a modulator of multiple S1P receptors) alleviated osteoporosis and suppressed arthritis in animals. This study determined the effect of FTY720 on proinflammatory cytokine production and osteoclastogenesis in murine bone marrow cells with or without A. actinomycetemcomitans stimulation. METHODS: Murine bone marrow-derived monocytes and macrophages (BMMs) were treated with vehicle ethanol or FTY720, and were either unstimulated or stimulated for 0.5 to 6 h with A. actinomycetemcomitans. The protein levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha in the media of BMMs were quantified by enzyme-linked immunosorbent assay (ELISA). Protein expressions, including phosphorylated phosphoinositide 3 kinase (p-PI3K), p-Akt, p-extracellular signal-regulated kinase (p-ERK), PI3K, Akt, and ERK were evaluated by Western blot. In addition, murine bone marrow derived pre-osteoclasts were treated with macrophage colony-stimulating factor (M CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) for three days. Then the cells were treated with either vehicle or FTY720 and were either unstimulated or stimulated with A. actinomycetemcomitans for 4 to 24 h. Control cells were treated with M-CSF alone with or without bacterial stimulation. Osteoclasts were stained by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of osteoclastogenic factors, including nuclear factor of activated T-cells cytoplasmic calcineurin-dependent 1 (Nfatc1), cathepsin K (Ctsk), acid phosphatase 5 (Acp5), osteoclast-associated receptor (Oscar), and RANKL were quantified by quantitative real-time polymerase chain reaction (PCR). RESULTS: FTY720 dose-dependently inhibited IL-1beta, IL-6, and TNF-alpha protein levels induced by A. actinomycetemcomitans in BMMs compared with controls. Additionally, FTY720 attenuated p-PI3K, p-Akt, and p-ERK expressions induced by A. actinomycetemcomitans. Furthermore, FTY720 suppressed osteoclastogenesis in bone marrow-derived pre-osteoclasts with or without bacterial stimulation and reduced the mRNA levels of Nfatc1, Ctsk, Acp5, and Oscar, but not RANKL in bone marrow-derived pre-osteoclasts. CONCLUSION: FTY720 inhibited proinflammatory cytokine production and suppressed osteoclastogenesis, supporting FTY720 as a potential therapy for inflammatory bone loss diseases. PMID- 26138338 TI - A conserved role for calpains during myoblast fusion. AB - Myoblast fusion is a key step during skeletal muscle differentiation as it enables the formation of contractile fibers. Calpains have been implicated in some aspects of myogenesis in mammals, but whether they exert a conserved function during myoblast fusion has not been investigated. Here, we studied Calpain function in two models of myogenesis: in vitro analysis of chick myogenic cultures and in vivo analysis of Drosophila melanogaster muscle development. First we showed that Calpain A is important for fly muscle function. In addition, Calpain A knockdown reduced lateral body wall muscle length and width, as well as the number of nuclei in dorsal oblique muscles, consistent with fewer cells fusing to form fibers. Treatment of chick cultures with a selective Calpain inhibitor led to the formation of thinner myotubes containing a reduced number of nuclei, consistent with decreased myoblast fusion. Dynamic changes in IkappaBalpha labeling and transfection with a dominant-negative IkappaBalpha suggest a role for the NFkappaB pathway during chick myogenesis and a possible role of Calpains in attenuating NFkappaB signals that restrict myoblast fusion. Our data suggest that different model organisms may be used to study the role of Calpains in regular myogenesis and Calpain-related muscular degenerative disorders. PMID- 26138339 TI - Stabilisation of a loosened femoral gamma nail by percutaneous cement injection (cementoplasty): a new technique. AB - Surgical repair of pertrochanteric and subtrochanteric fractures in the elderly is usually achieved using an endomedullary nail. Unfortunately, even today, some of the patients who undergo this intervention develop periprosthetic bone absorption over time that can lead to loosening of the prosthesis, resulting in pain, joint instability and the need for revision surgery. Surgical revision is hindered by potential complications related to patients' existing underlying medical conditions. It is often the case that these patients are weak and present comorbidities, which can lead to an absolute contraindication to surgery. An interesting alternative could be the stabilisation by percutaneous injection of cement (cementoplasty) in the periprosthetic space under CT and fluoroscopic guidance. In patients with absolute contraindication we performed percutaneous cementoplasty as treatment for femoral prosthesis loosening. Our procedure was technically a success following the end of the intervention period (follow-up: 6 months). The patient no longer experienced significant pain and showed stability of the prosthesis, as demonstrated by CT. PMID- 26138341 TI - An important anniversary: 150 years since Mendel's laws of inheritance made their first public appearance. PMID- 26138340 TI - Imaging appearance of entrapped periosteum within a distal femoral Salter-Harris II fracture. AB - Salter Harris II fractures of the distal femur are associated with a high incidence of complications, especially premature physeal closure. Many risk factors for this high rate of premature physeal closure have been proposed. More recently, entrapment of periosteum within the physis has been suggested as an additional predisposing factor for premature physeal closure. The radiographic diagnosis of entrapped soft tissues, including periosteum, can be suggested in the setting of a Salter-Harris II fracture when the fracture does not reduce and physeal widening >3 mm remains. We report a patient who sustained a distal femoral Salter-Harris II fracture following a valgus injury. The patient had persistent distal medial physeal widening >5 mm following attempted reduction. A subsequent MRI revealed a torn periosteum entrapped within the distal femoral physis. Following removal of the periosteum, the patient developed a leg length discrepancy which required physiodesis of the contralateral distal femur. We present this case to raise awareness of the importance of having a high index of suspicion of periosteal entrapment in the setting of Salter-Harris II fractures since most consider entrapped periosteum an indication for surgery. PMID- 26138342 TI - Cell membrane permeabilization by 12-ns electric pulses: Not a purely dielectric, but a charge-dependent phenomenon. AB - Electric pulses of a few nanoseconds in duration can induce reversible permeabilization of cell membrane and cell death. Whether these effects are caused by ionic or purely dielectric phenomena is still discussed. We address this question by studying the impact of conductivity of the pulsing buffer on the effect of pulses of 12 ns and 3.2 MV/m on the DC-3F mammalian cell line. When pulses were applied in a high-conductivity medium (1.5 S/m), cells experienced both reversible electropermeabilization and cell death. On the contrary, no effect was observed in the low-conductivity medium (0.1 S/m). Possible artifacts due to differences in viscosity, temperature increase or electrochemical reactions were excluded. The influence of conductivity reported here suggests that charges still play a role, even for 12-ns pulses. All theoretical models agree with this experimental observation, since all suggest that only high conductivity medium can induce a transmembrane voltage high enough to induce pore creation, in turn. However, most models fail to describe why pulse accumulation is experimentally required to observe biological effects. They mostly show no increase of permeabilization with accumulation of pulses. Currently, only one model properly describes pulse accumulation by modeling diffusion of the altered membrane regions. PMID- 26138343 TI - Microbial community analysis in a long-term membrane-less microbial electrolysis cell with hydrogen and methane production. AB - A single-chamber microbial electrolysis cell (MEC) aiming at hydrogen production with acetate as sole carbon source failed due to methanogenesis build-up despite the significant amount of 2-bromoethanesulfonate (BES) dosage, 50 mM. Specific batch experiments and a thorough microbial community analysis, pyrosequencing and qPCR, of cathode, anode and medium were performed to understand these observations. The experimental data rebuts different hypothesis and shows that methanogenesis at high BES concentration was likely due to the capacity of some Archaea (hydrogen-oxidizing genus Methanobrevibacter) to resist high BES concentration up to 200 mM. Methanobrevibacter, of the Methanobacteriales order, represented almost the 98% of the total Archaea in the cathode whereas Geobacter was highly abundant in the anode (72% of bacteria). Moreover, at higher BES concentration (up to 200 mM), methanogenesis activity decreased resulting in an increase of homoacetogenic activity, which challenged the performance of the MEC for H2 production. PMID- 26138344 TI - Osteogenic/angiogenic dual growth factor delivery microcapsules for regeneration of vascularized bone tissue. AB - Growth factors (GFs) are major biochemical cues for tissue regeneration. Herein, a novel dual GF delivery system is designed composed of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and alginate microcapsules (MCs) via an electrodropping method. While bone morphogenetic protein (BMP)-2 is encapsulated in the PLGA NPs, vascular endothelial growth factor (VEGF) is included in the alginate MCs, where BMP-2-loaded PLGA NPs are entrapped together in the fabrication process. The initial loading efficiencies of BMP-2 and VEGF are 78% +/- 3.6% and 43% +/- 1.7%, respectively. When our dual GF-loaded MCs are assessed for in vitro osteogenesis of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on 2D and 3D environment, MCs contribute to much better UCB-MSCs osteogenesis as confirmed by von Kossa staining, immunofluorescence (osteocalcin, collagen 1), calcium content measurement, and osteogenic markers expression. In addition, when dual GF-encapsulated MCs are combined with collagen and then applied to 8 mm diameter rat calvarial defect model, the positive effects on vascularized bone regeneration are much more pronounced; micro computed tomography (CT) and histology analyses exhibit 82.3% bone healing coupled with 12.6% vessel occupied area. Put together, current study indicates a synergistic effect of BMP-2/VEGF and highlights the great potential of dual GF delivery modality (PLGA NPs-in-MC) for regeneration of vascularized bone. PMID- 26138345 TI - Ixazomib for the treatment of multiple myeloma. AB - INTRODUCTION: Proteasome inhibition is a mainstay in the treatment of multiple myeloma (MM). Bortezomib, the first proteasome inhibitor (PI) approved for MM therapy, has shown efficacy in relapsed/refractory patients and in the front-line setting. Among second-generation PIs, MLN9708 ( ixazomib ) is the first oral compound to be evaluated in MM treatment and has shown improvement in pharmacokinetic and pharmacodynamic parameters compared with bortezomib with a similar efficacy in the control of myeloma growth and in the prevention of bone loss. AREAS COVERED: In this review, the authors discuss the rationale for use of PIs. They then summarize the clinical development of ixazomib in MM, from initial Phase I to Phase II studies as a monotherapy and in combination with other chemotherapeutics. EXPERT OPINION: Preliminary data of Phase I/II trials showed that ixazomib had a good safety profile and exerted anti-myeloma activity as a single agent in relapsed/refractory patients. Furthermore, ixazomib also had efficacy in patients who were refractory to bortezomib. Its use in combination with lenalidomide and dexamethasone was shown to be an effective and well tolerated regimen in up-front treatment leading to minimal residual disease negativity in a significant number of patients. Results of Phase III trials, evaluating ixazomib in induction or maintenance therapy, are awaited. PMID- 26138346 TI - TRAIL-receptor preferences in pancreatic cancer cells revisited: Both TRAIL-R1 and TRAIL-R2 have a licence to kill. AB - BACKGROUND: TRAIL is a potent and specific inducer of apoptosis in tumour cells and therefore is a possible new cancer treatment. It triggers apoptosis by binding to its cognate, death-inducing receptors, TRAIL-R1 and TRAIL-R2. In order to increase its activity, receptor-specific ligands and agonistic antibodies have been developed and some cancer types, including pancreatic cancer, have been reported to respond preferentially to TRAIL-R1 triggering. The aim of the present study was to examine an array of TRAIL-receptor specific variants on a number of pancreatic cancer cells and test the generality of the concept of TRAIL-R1 preference in these cells. METHODS: TRAIL-R1 and TRAIL-R2 specific sTRAIL variants were designed and tested on a number of pancreatic cancer cells for their TRAIL-receptor preference. These sTRAIL variants were produced in HEK293 cells and were secreted into the medium. After having measured and normalised the different sTRAIL variant concentrations, they were applied to pancreatic and control cancer cells. Twenty-four hours later apoptosis was measured by DNA hypodiploidy assays. Furthermore, the specificities of the sTRAIL variants were validated in HCT116 cells that were silenced either for TRAIL-R1 or TRAIL-R2. RESULTS: Our results show that some pancreatic cancer cells use TRAIL-R1 to induce cell death, whereas other pancreatic carcinoma cells such as AsPC-1 and BxPC-3 cells trigger apoptosis via TRAIL-R2. This observation extended to cells that were naturally TRAIL-resistant and had to be sensitised by silencing of XIAP (Panc1 cells). The measurement of TRAIL-receptor expression by FACS revealed no correlation between receptor preferences and the relative levels of TRAIL-R1 and TRAIL-R2 on the cellular surface. CONCLUSIONS: These results demonstrate that TRAIL-receptor preferences in pancreatic cancer cells are variable and that predictions according to cancer type are difficult and that determining factors to inform the optimal TRAIL-based treatments still have to be identified. PMID- 26138347 TI - Underuse of surgical resection among elderly patients with early-stage pancreatic cancer. AB - BACKGROUND: Although surgery improves the health care quality and outcomes of patients with early-stage pancreatic cancer, these patients' operative resection rate has been historically low. We sought to identify factors that are associated with operative resection in this patient population. METHODS: In this retrospective population-based study, we used Texas Cancer Registry-linked and Surveillance and Epidemiology End Results Program-linked Medicare data to study factors potentially associated with operative resection in patients age >= 66 years who had been diagnosed with localized pancreatic cancer between January 1, 2001, and December 31, 2009. Variables were assessed using multivariate logistic regression and Cox proportional hazards regression models. We used Kaplan-Meier analysis to assess the effect of operative resection on survival rate. RESULTS: Of 1,501 patients with localized pancreatic cancer, only 340 (22.7%) underwent operation. Patients were more likely to undergo surgery if they were young, had small tumors, had low-grade tumors, and had nodal negativity (P < .05). Compared with patients who did not undergo surgery, patients who underwent surgery had a significantly higher 5-year overall survival rate (25.0 vs 2.3%; P < .0001) and had a higher median survival time (24.3 vs 5.8 months). CONCLUSION: The rate of operative resection of early-stage pancreatic cancer did not increase significantly from 2001 to 2009. Although we identified several variables associated with operative resection, why the percentage of patients with localized pancreatic cancer who undergo definitive surgery is so low remains unclear. PMID- 26138348 TI - Remineralization of demineralized bone matrix in critical size cranial defects in rats: A 6-month follow-up study. AB - The key drawback of using demineralized bone matrix (DBM) is its low initial mechanical stability due to the severe depletion of mineral content. In the present study, we investigated the long-term regeneration of DBM in a critical size bone defect model and investigated the remineralization after 6 months. Bone defects were created in the cranium of male Wistar rats which were filled with DBM or left empty as negative control. In vivo bone formation was monitored with computed tomography after 11, 19, and 26 weeks postoperatively. After 6 months, parietal bones were subjected to micro-CT. Mineral content was determined with spectrophotometric analysis. After 11 weeks the DBM-filled bone defects were completely closed, while empty defects were still open. Density of the DBM treated group increased significantly while the controls remained unchanged. Quantitative analysis by micro-CT confirmed the in vivo results, bone volume/tissue volume was significantly lower in the controls than in the DBM group. The demineralization procedure depleted the key minerals of the bone to a very low level. Six months after implantation Ca, P, Na, Mg, Zn, and Cr contents were completely restored to the normal level, while K, Sr, and Mn were only partially restored. The remineralization process of DBM is largely complete by the 6th month after implantation in terms of bone density, structure, and key mineral levels. Although DBM does not provide sufficient sources for any of these minerals, it induces a faster and more complete regeneration process. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1336 1342, 2016. PMID- 26138349 TI - No Ground for Advocating that Korean Eunuchs Lived Longer than Intact Men. PMID- 26138350 TI - Personal Values and Moral Disengagement Promote Aggressive and Rule-Breaking Behaviours in Adolescents With Disruptive Behaviour Disorders: A Pilot Study. AB - The pilot study presented in this article investigated the role of moral cognitive features in understanding aggressive and rule-breaking behaviours in adolescents with Disruptive Behaviour Disorder (DBD). We collected two samples. The community sample was composed of 85 adolescents, whereas the DBD sample was composed of 30 adolescents. Compared with a community sample, adolescents with DBD are more inclined to use moral disengagement (MD) to legitimize their aggressive and rule-breaking behaviours. Moreover, regression models showed that self-enhancement values and MD foster externalizing behaviours taking into account both gender and the group they belonged to, that is, either clinical or community sample. Instead, self-transcendence values could prevent externalizing problems by inhibiting MD. Implications of these findings for assessment and therapeutic interventions are discussed. PMID- 26138351 TI - Social Relationships and Group Dynamics Inside a Community Correction Facility for Women. AB - This article presents research on women's perceptions and experiences residing in a female community correction facility. Qualitative interview data and field observations are used to examine resident relationships, perceptions of on-site group treatment, and benefits of receiving off-site treatment. Findings from this study indicate an overwhelming feeling of tension and lack of trust among residents, resulting in most women withdrawing from social interactions. Relationship dynamics also played a role in women's participation during on-site group treatment and desiring off-site treatment. This study supports the need to create, and sustain, therapeutic environments within community correction settings for women. PMID- 26138352 TI - Confirmatory Factor Analysis of the Antisocial Process Screening Device. AB - The main aim of the present study was to examine the factor structure, internal consistency, and some additional psychometric properties of the Antisocial Process Screening Device-Self-Report (APSD-SR) among a large forensic sample of incarcerated male juvenile offenders ( N = 438). The results, based on this forensic sample, support the use of the APSD-SR in terms of its factor structure, and internal consistency despite the fact an item had to be removed from the callous-unemotional (CU) dimension. Statistically significant positive associations were found with measures of psychopathic traits, CU traits, narcissism, and aggression, as well as negative associations with a measure of empathy. Findings provide support for the use of the APSD-SR among the incarcerated male juvenile offender population. PMID- 26138353 TI - In vitro Antifungal Activity and Mechanism of Action of Tea Polyphenols and Tea Saponin against Rhizopus stolonifer. AB - The in vitro antifungal activities and mechanism of action of tea polyphenols (TP), tea saponin (TS) and their combination were evaluated against Rhizopus stolonifer. The results showed that both TP and TS inhibited the mycelial growth in a dose-dependent manner, and their combination at the ratio of 7:3 exhibited synergistic antifungal interaction. We also observed that the treatment of TP or TS significantly induced the production of H2O2 and resulted in membrane lipid peroxidation, thus leading to an increase in cell membrane permeability and the leakage of K(+), soluble protein and soluble sugar. Moreover, combining them for treatment increased the induction of H2O2 production and oxidative damage. Scanning electron microscopic observations also showed the damage to the hyphal cell structure. It was concluded that TP, TS and their combination inhibit the growth of R. stolonifer through the induction of H2O2 production, leading to cell membrane oxidative damage and intracellular constituent leakage. These findings suggest that TP and TS can potentially be used as an alternative to control postharvest fruit diseases caused by R. stolonifer. PMID- 26138354 TI - Distributed and decentralized state estimation in gas networks as distributed parameter systems. AB - In this paper, a framework for distributed and decentralized state estimation in high-pressure and long-distance gas transmission networks (GTNs) is proposed. The non-isothermal model of the plant including mass, momentum and energy balance equations are used to simulate the dynamic behavior. Due to several disadvantages of implementing a centralized Kalman filter for large-scale systems, the continuous/discrete form of extended Kalman filter for distributed and decentralized estimation (DDE) has been extended for these systems. Accordingly, the global model is decomposed into several subsystems, called local models. Some heuristic rules are suggested for system decomposition in gas pipeline networks. In the construction of local models, due to the existence of common states and interconnections among the subsystems, the assimilation and prediction steps of the Kalman filter are modified to take the overlapping and external states into account. However, dynamic Riccati equation for each subsystem is constructed based on the local model, which introduces a maximum error of 5% in the estimated standard deviation of the states in the benchmarks studied in this paper. The performance of the proposed methodology has been shown based on the comparison of its accuracy and computational demands against their counterparts in centralized Kalman filter for two viable benchmarks. In a real life network, it is shown that while the accuracy is not significantly decreased, the real-time factor of the state estimation is increased by a factor of 10. PMID- 26138355 TI - Whole-exome sequencing improves the diagnosis yield in sporadic infantile spasm syndrome. AB - Infantile spasms syndrome (ISs) is characterized by clinical spasms with ictal electrodecrement, usually occurring before the age of 1 year and frequently associated with cognitive impairment. Etiology is widely heterogeneous, the cause remaining elusive in 40% of patients. We searched for de novo mutations in 10 probands with ISs and their parents using whole-exome sequencing (WES). Patients had neither consanguinity nor family history of epilepsy. Common causes of ISs were excluded by brain magnetic resonance imaging (MRI), metabolic screening, array-comparative genomic hybridization (CGH) and testing for mutations in CDKL5, STXBP1, and for ARX duplications. We found a probably pathogenic mutation in four patients. Missense mutations in SCN2A (p.Leu1342Pro) and KCNQ2 (p.Ala306Thr) were found in two patients with no history of epilepsy before the onset of ISs. The p.Asn107Ser missense mutation of ALG13 had been previously reported in four females with ISs. The fourth mutation was an in-frame deletion (p.Phe110del) in NR2F1, a gene whose mutations cause intellectual disability, epilepsy, and optic atrophy. In addition, we found a possibly pathogenic variant in KIF3C that encodes a kinesin expressed during neural development. Our results confirm that WES improves significantly the diagnosis yield in patients with sporadic ISs. PMID- 26138356 TI - Amelioration of the adverse effects of prednisolone by rituximab treatment in adults with steroid-dependent minimal-change nephrotic syndrome. AB - BACKGROUND: We previously demonstrated the efficacy of single-dose 6-monthly rituximab infusions in 25 adults with steroid-dependent minimal-change nephrotic syndrome. Herein, we assessed the safety of rituximab treatment and its effect in ameliorating the adverse effects of prednisolone (PRED) in a larger study sample. METHODS: We treated 54 adult patients with four single-dose 6-monthly infusions of rituximab (375 mg/m(2) BSA per dose). We compared the adverse effects of PRED (osteoporosis, hypertension, and diabetes mellitus) between the first rituximab infusion (baseline) and the end of the 24-month observation period. In addition, we examined the adverse effects of rituximab during the same period. RESULTS: The PRED dose was significantly lower at 24 months than at the baseline. The bone density was significantly higher at 24 months as compared to the baseline value (Z score -1.8 vs. -1.1; p < 0.05). Blood pressure at 24 months was significantly lower than that at the baseline (120.9/74.4 vs. 111.8/70.3 mm Hg; p < 0.05). Eight patients with diabetes mellitus showed improved glycemic control at 24 months as compared to that at the baseline. There were no severe adverse effects of rituximab. However, mild infusion reactions occurred in 31 patients (57%). The frequency of the infusion reactions decreased significantly with every successive infusion. CONCLUSION: Rituximab treatment was effective and safe in patients with steroid-dependent nephrotic syndrome, allowed reduction of the PRED dose, and ameliorated the adverse effects of PRED. It may be preferentially used in patients at a risk of the adverse effect of PRED. PMID- 26138358 TI - A novel benzoxazine/cyanate ester blend with sea-island phase structures. AB - A novel cardanol-based benzoxazine (C-BOZ)/bisphenol A dicyanate ester (BADCy) blend with sea-island phase structures was successfully prepared via reaction induced phase separation. The introduction of a long-chain alkyl group on the benzene ring significantly enhanced the thermodynamic differences between C-BOZ and BADCy. With the increase of the BADCy content, the Flory-Huggins interaction parameter (chi) of the blend decreased. By adjusting the ratio of the two components, sea-island phase separations were observed in C-BOZ/BADCy blends during the curing process. The dispersed phase was a C-BOZ rich phase, while the matrix was the crosslinked network composed of triazine rings and ring-opened C BOZ. On the DMA curves of 9/1, 8/2 and 7/3 cured blends, there were two distinct Tgs. But with the increase of the BADCy content, the extent of phase separation was reduced. When the ratio reached 5/5, there was only one Tg because the viscosity of the blend was too high for phase separation to occur. PMID- 26138357 TI - Involvement of the renin-angiotensin system in the development of nephrogenic systemic fibrosis-like lesions in the RenTag mouse model. AB - BACKGROUND: Renin-angiotensin system (RAS) activation increases angiotensin II production stimulating profibrotic factors, especially in the setting of chronic kidney disease. Nephrogenic systemic fibrosis (NSF) has been associated with gadolinium (Gd) exposure and renal failure. RAS involvement in NSF is unclear compared to transforming growth factor beta and Smad. RenTag mice were chosen to investigate the role of RAS in NSF-like dermal fibrosis because they demonstrated dermal fibrosis at birth, perturbations of RAS in subcutaneous tissue, and renal failure within 4 weeks of age. METHODS: Wild-type and RenTag mice were injected weekly with a supratherapeutic dose of intravenous gadodiamide (3.0 mmol/kg body weight) and killed at 12 weeks of age for skin and kidney histology. RESULTS: RenTag mice had elevated BUN levels, pitted kidneys, and glomerular damage. RenTag mice skin revealed an increased density of fibroblasts, no mucopolysaccharide deposits, and increased collagen fibril density regardless of Gd exposure. Skin and kidney histopathology of wild-type mice were normal regardless of Gd exposure. CD34 positivity was higher in RenTag compared to wild type. CONCLUSIONS: Since RenTag dermal lesions remained unchanged after gadolinium exposure in the setting of renal failure, this animal model suggests perturbations of subcutaneous RAS may be involved in Gd-naive dermal fibrosis. PMID- 26138359 TI - Post-procedure bleeding in interventional radiology. AB - Following interventional radiology procedures, bleeding can occur in 0.5 to 4% of the cases. Risk factors are related to the patient, to the procedure, and to the end organ. Bleeding is treated usually by interventional radiologists and consists mainly of embolization. Bleeding complications are preventable: before the procedure by checking hemostasis, during the procedure by ensuring the accurate puncture site (with ultrasound or fluoroscopy guidance) or by treating the puncture path using gelatin sponge, curaspon((r)), biological glue or thermocoagulation, and after the procedure by carefully monitoring the patients. PMID- 26138361 TI - 1,4-Diketones from Cross-Conjugated Dienones: Potassium Permanganate-Interrupted Nazarov Reaction. AB - A domino potassium permanganate-interrupted Nazarov reaction to yield syn-2,3 disubstituted 1,4-diketones via a decarbonylative cleavage of the Nazarov oxyallyl intermediate, believed to be without precedent, is presented. This process allows syn substituents to be established stereospecifically on the 2 carbon bridge connecting the ketone carbonyl carbons, and the formation of one carbon-carbon and two carbon-oxygen bonds. Two carbon-carbon bonds are cleaved in this process. PMID- 26138360 TI - A descriptive study to provide evidence of the teratogenic and cellular effects of sibutramine and ephedrine on cardiac- and liver-tissue of chick embryos. AB - Exposure to drugs during pregnancy is a major concern, as some teratogenic compounds can influence normal foetal development. Although the use of drugs during pregnancy should generally be avoided, exposure of the developing foetus to teratogens may occur unknowingly since these compounds may be hidden in products that are being marketed as "all natural." The aim of the current study was to investigate the possible teratogenic and cellular effects of sibutramine-a serotonin-norepinephrine reuptake inhibitor used in the treatment of obesity-on the heart and liver tissue of chick embryos. Ephedrine was used as a positive control. The chick embryo model was chosen because it has been used in studying developmental and experimental biology and teratology with great success. The embryos were exposed to three different concentrations of sibutramine and ephedrine respectively. The results obtained revealed that both compounds exhibited embryotoxicity when compared to the control groups. Liver and heart tissue of the exposed embryos was severely affected by these compounds in a dose related manner. Morphology similar to that of muscle dystrophy was observed in the heart, where the muscle tissue was infiltrated by adipose and connective tissue. Severe liver steatosis was also noted. A more in-depth investigation into the molecular pathways involved might provide more information on the exact mechanism of toxicity of these products influencing embryonic development. PMID- 26138362 TI - Inhibition of activin A signalling in a mouse model of pre-eclampsia. AB - INTRODUCTION: Pre-eclampsia remains a major cause of maternal and fetal morbidity and mortality. Despite intensive research over the last 50 years, significant therapeutic advances have yet to be realised. We recently reported on the role of activin A in the pathophysiology of pre-eclampsia, whereby a pre-eclampsia-like disease state was induced in pregnant mice through activin A infusion. Using the same animal model, the effects of inhibiting activin A signalling on this pre eclampsia-like disease state have now been assessed with low molecular weight compounds structurally related to activin-receptor-like kinase (ALK) inhibitors. METHODS: 23 synthetic compounds were screened for ability to reduce activin A induced free radical production in HUVECs. Further, following administration of activin A (50 MUg) via a subcutaneous mini-osmotic pump from day 10 of pregnancy, the most active inhibitor, MKP-1-140A, (1 mg/kg) was also concomitantly administered via subcutaneous injections. RESULTS: Significant reductions in activin A-induced systolic blood pressure and urine albumin:creatinine ratio were observed with inhibitor-treated animals. However, these findings were accompanied by sustained elevation of liver enzymes and albumin extravasation in the brains of pregnant mice that received MKP-1-140A. Furthermore, inhibition of activin A signalling with MKP-1-140A failed to rescue fetal growth restriction, and treatment with MKP-1-140A alone resulted in craniofacial and karyotypic abnormalities. DISCUSSION: These data indicate that whilst inhibition of activin A signalling by the low molecular weight ALK kinase inhibitor, MKP-1-140A, reduced some of the physiological manifestations of pre-eclampsia, the potential for serious maternal and fetal side effects may preclude it from clinical applications. PMID- 26138363 TI - Neurotrophin levels in different regions of the placenta and their association with birth outcome and blood pressure. AB - INTRODUCTION: Our recent study in preeclampsia indicates differential oxidative stress in various regions of the placenta. Oxidative stress is known to influence neurotrophin levels. We therefore hypothesize that placental regional differences in oxidative stress will also lead to differences in neurotrophin levels. METHODS: The current study examines the levels of neurotrophins, brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in different regions of the placenta in 50 normotensive control women and 47 women with preeclampsia (21 delivering at term and 26 delivering preterm). Placentae were collected from four different regions: central maternal (CM), central fetal (CF), peripheral maternal (PM) and peripheral fetal (PF). RESULTS: BDNF levels were higher in CF region as compared to CM (p < 0.01), PM (p < 0.01) and PF (p < 0.05) regions of the placenta in the control group. There was no regional change in NGF levels in any of the groups. Analysis between groups indicated higher NGF levels in CM (p < 0.01), PM (p < 0.05) and PF (p < 0.01) regions of preterm preeclampsia group as compared to control. Negative association of NGF levels in CM, CF and PM regions with baby weight and in CF, PM and PF regions with baby length was observed. NGF levels in all four regions were positively associated with systolic blood pressure. DISCUSSION: Our data indicates regional differences in levels of BDNF only in normotensive control but not in preeclampsia group. Higher NGF levels in preterm preeclampsia may be a response to increased oxidative stress. This may have implications for altered placental development in preeclampsia. PMID- 26138364 TI - First trimester placental markers in oocyte donation pregnancies. AB - INTRODUCTION: This study investigates the hypothesis that placenta works differently in oocyte donation (OD) compared to spontaneous pregnancies. To verify this hypothesis we examine the first trimester maternal serum levels of free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A). Then we evaluated for potential differences of Down syndrome screening between OD pregnancies, in vitro fertilization/intracytoplasmic sperm injection pregnancies with autologous oocytes (IVF/ICSI) and spontaneous pregnancies. METHODS: We analyze 13624 spontaneously conceived pregnancies (Controls), 171 oocyte donation pregnancies (OD IVF/ICSI) and 76 IVF pregnancies with autologous oocytes (Autologous IVF/ICSI). Furthermore, we collect a cohort of 802 spontaneously conceived age-matched pregnancies, in order to evaluate how older uteri contribute to explain the changes in markers concentrations (Age-matched controls We compare the multiples of the median (MoM) of free beta-hCG and PAPP-A and nuchal translucency. RESULTS: Free beta-hCG levels are significantly higher both in OD IVF/ICSI pregnancies (1.44 +/- 1.06 MoM) and Autologous IVF/ICSI (1.48 +/- 1.02 MoM) compared to Controls (1.15 +/- 0.84 MoM; p < 0.05) and Age-matched Controls (1.18 +/- 0.98 MoM; p < 0.05). PAPP-A levels do not significantly differ among the four groups. Significantly lower nuchal translucency is detected in Controls (1.41 +/- 0.36 mm) compared to OD IVF/ICSI (1.46 +/- 0.44 mm; p < 0.05), in Autologous IVF/ICSI (1.51 +/- 0.34 mm; p < 0.05) and Age-matched Controls (1.44 +/- 0.42 mm; p < 0.05). DISCUSSION: Oocyte donation pregnancies (OD IVF/ICSI) are significantly related to altered maternal serum placenta marker levels. These alterations might be due to the IVF technique. PMID- 26138365 TI - Carbohydrate Malabsorption and Putative Carbohydrate-Specific Small Intestinal Bacterial Overgrowth: Prevalence and Diagnostic Overlap Observed in an Austrian Outpatient Center. AB - BACKGROUND/AIMS: While lactose malabsorption is a well-investigated condition, few epidemiologic data are available for fructose and sorbitol malabsorption. The aim of this study was to assess the prevalence rates for primary lactose malabsorption, fructose and sorbitol malabsorption, and carbohydrate-specific small intestinal bacterial overgrowth (cs-SIBO) in an Austrian outpatient center. METHODS: In total, 306 adult patients, who were primarily referred with suspected carbohydrate malabsorption by general practitioners to our outpatient clinic, underwent genetic testing (C/T-13910 polymorphism) for primary lactose malabsorption, and a combined hydrogen (H2)/methane (CH4) breath test for fructose (25 g) and sorbitol (12.5 g) malabsorption. Cohen's kappa (kappa) was calculated for agreement between positive breath test results and self-reported symptoms during the test. RESULTS: Seventy-eight (25.49%) patients were C/C-13910 homozygotes, indicating primary lactose malabsorption. Thirty-four (11.11%) and 57 (18.63%) patients were classified as fructose and sorbitol malabsorbers. Cohen's kappa measuring agreements between positive fructose and sorbitol breath test results and self-reported symptoms during the test were 0.33 and 0.49, respectively. Twenty-nine (9.50%) patients with an early H2/CH4 peak (i.e. within 60 minutes after fructose and/or sorbitol ingestion) were diagnosed with cs-SIBO. CONCLUSION: In Austria, carbohydrate malabsorption is a frequent condition in patients referred by general practitioners to carbohydrate malabsorption testing. PMID- 26138367 TI - Chemical profiling and antioxidant activity of Bolivian propolis. AB - BACKGROUND: Propolis is a relevant research subject worldwide. However, there is no information so far on Bolivian propolis. Ten propolis samples were collected from regions with high biodiversity in the main honey production places in Bolivia and were analyzed for their total phenolics (TP), flavonoids (TF) and antioxidant activity. The chemical profiles of the samples were assessed by TLC, HPLC-DAD, HPLC-DAD-MS/MS(n) and NMR analysis. RESULTS: TP, TF, TLC and NMR analysis showed significant chemical differences between the samples. Isolation of the main constituents by chromatography and identification by HPLC-DAD MS/MS(n) achieved more than 35 constituents. According to their profiles, the Bolivian propolis can be classified into phenolic-rich and triterpene-rich samples. Propolis from the valleys (Cochabamba, Chuquisaca and Tarija) contained mainly prenylated phenylpropanoids, while samples from La Paz and Santa Cruz contained cycloartane and pentacyclic triterpenes. Phenolic-rich samples presented moderate to strong antioxidant activity while the triterpene-rich propolis were weakly active. CONCLUSION: High chemical diversity and differential antioxidant effects were found in Bolivian propolis. Our results provide additional evidence on the chemical composition and bioactivity of South American propolis. PMID- 26138366 TI - Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma. AB - Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS. PMID- 26138369 TI - Reply to 'Effects of food on pharmacokinetics of immediate release oral formulations'. PMID- 26138368 TI - NF-kappaB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis. AB - NF-kappaB is constitutively activated in psoriatic epidermis. However, how activated NF-kappaB promotes keratinocyte hyperproliferation in psoriasis is largely unknown. Here we report that the NF-kappaB activation triggered by inflammatory cytokines induces the transcription of microRNA (miRNA) miR-31, one of the most dynamic miRNAs identified in the skin of psoriatic patients and mouse models. The genetic deficiency of miR-31 in keratinocytes inhibits their hyperproliferation, decreases acanthosis and reduces the disease severity in psoriasis mouse models. Furthermore, protein phosphatase 6 (ppp6c), a negative regulator that restricts the G1 to S phase progression, is diminished in human psoriatic epidermis and is directly targeted by miR-31. The inhibition of ppp6c is functionally important for miR-31-mediated biological effects. Moreover, NF kappaB activation inhibits ppp6c expression directly through the induction of miR 31, and enhances keratinocyte proliferation. Thus, our data identify NF-kappaB induced miR-31 and its target, ppp6c, as critical factors for the hyperproliferation of epidermis in psoriasis. PMID- 26138370 TI - Cerebral Accidents in Pediatric Diabetic Ketoacidosis: Different Complications and Different Evolutions. AB - Diabetic ketoacidosis (DKA) may be associated with neurologic complications: the most common is cerebral edema while the risk of venous and arterial stroke is rare. There is a pathogenetic link between DKA, hypercoagulability and stroke, whose risk is underestimated by clinicians. Our cases present a wide spectrum of cerebral accidents during DKA, the first one being diffuse cerebral edema, the second one venous stroke after 5 days of DKA resolution, while the third one multifocal edema suspected to be extrapontine myelinolysis although without electrolyte imbalance. Our cases suggest that DKA requires very accurate treatment, particularly at an early age, and it can be complicated by cerebral accidents even with appropriate medical care. PMID- 26138372 TI - A clinical clerkship collaborative program in Taiwan: Acquiring core clinical competencies through patient care responsibility. AB - BACKGROUND/PURPOSE: Traditionally, clinical clerkship training in Taiwan does not provide medical students with sufficient patient care responsibilities and often results in inadequate clinical skills. METHODS: We implemented a pilot clerkship program at a comprehensive cancer center that emphasizes core clinical competency through direct patient care and dedicated faculty and mentors. Students were an integral part of the patient care team held accountable for providing coordinated and holistic care. Students' self-assessment of clinical competencies, faculty evaluation, and objective structured clinical examination were compared against their peers trained by traditional clerkship at a main teaching hospital. RESULTS: Fifty medical students completed the clerkship program in the first 3 years. At the end of the clerkship, participants rated themselves significantly higher than their peers in almost all patient care and clinical skill domains. The most significant areas included physical examination, clinical reasoning, developing management plan, holistic approach, handling ethical issues, and time management skills. The students rated their clerkship teachers significantly higher in time spent with students, skills and enthusiasm in teaching, as well as giving students appropriate patient care responsibilities. There was no significant difference in the end-of-clerkship objective structured clinical examination performance, but participants of the program achieved better grades in their subsequent internship. CONCLUSION: This pilot collaborative program presented a successful model for clinical education in the teaching of core clinical competencies through direct patient care responsibilities at the clerkship stage. It is hoped that the project will become a catalyst for medical education reform in Taiwan and regions with similar traditions. PMID- 26138371 TI - Utility of spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) to non-invasively diagnose burn depth in a porcine model. AB - Surgical intervention of second degree burns is often delayed because of the difficulty in visual diagnosis, which increases the risk of scarring and infection. Non-invasive metrics have shown promise in accurately assessing burn depth. Here, we examine the use of spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) for predicting burn depth. Contact burn wounds of increasing severity were created on the dorsum of a Yorkshire pig, and wounds were imaged with SFDI/LSI starting immediately after-burn and then daily for the next 4 days. In addition, on each day the burn wounds were biopsied for histological analysis of burn depth, defined by collagen coagulation, apoptosis, and adnexal/vascular necrosis. Histological results show that collagen coagulation progressed from day 0 to day 1, and then stabilized. Results of burn wound imaging using non-invasive techniques were able to produce metrics that correlate to different predictors of burn depth. Collagen coagulation and apoptosis correlated with SFDI scattering coefficient parameter [Formula: see text] and adnexal/vascular necrosis on the day of burn correlated with blood flow determined by LSI. Therefore, incorporation of SFDI scattering coefficient and blood flow determined by LSI may provide an algorithm for accurate assessment of the severity of burn wounds in real time. PMID- 26138373 TI - Mid- to long-term follow-up of pediatric patients with coronary artery fistula. AB - BACKGROUND/PURPOSE: To investigate mid- to long-term outcomes in children with coronary artery fistula (CAF). METHODS: We retrospectively reviewed the medical records of patients seen between September 1996 and August 2011. We enrolled those diagnosed with CAF via echocardiography (Philips SONOS 7500 system and Philips IE33) or angiography. The mean follow time was 42.58 +/- 3.4 months (range, 1-166 months). For comparative purposes, participants were grouped as acquired versus congenital, and symptomatic versus asymptomatic. We also measured the size of the coronary artery (CA) in patients with CA dilatation (CAD). RESULTS: Out of 122 CAF patients, spontaneous closure was detected in 37 patients at 21.59 +/- 3.45 months after diagnosis. This timeframe did not differ between the acquired and congenital groups (21.64 +/- 6.26 months vs. 21.57 +/- 4.15 months; p = 0.991). Ninety patients were asymptomatic and remained so; their spontaneous closure rate was 28.89%. Moreover, 24 patients had CAD, including 17 with Kawasaki disease and seven with congenital CAF. The CAs of all congenital CAF-plus-CAD patients were initially > 5 mm; these patients underwent percutaneous transcatheter intervention, and their CA sizes decreased significantly (6.11 +/- 0.79 mm vs. 3.76 +/- 0.36 mm; p = 0.002). CONCLUSION: With the advanced sensitivity of echocardiography, CAF can be detected more easily than ever before. Most patients with small CAFs are asymptomatic and may experience spontaneous closure. Therefore, management of CAF depends on symptoms; if patients are asymptomatic and have small CAFs, intervention may not be necessary, especially in acquired cases. However, if patients present with symptoms or persistent dilatation of the proximal CA, surgical or percutaneous closure should be performed. PMID- 26138374 TI - The Relationship of Transition Readiness, Self-Efficacy, and Adherence to Preferred Health Learning Method by Youths with Chronic Conditions. AB - BACKGROUND: Health care transition preparation, medication adherence, and self efficacy are important skills to achieve optimal health outcomes. It is unclear how pediatric patients with chronic conditions obtain health information that may impact the acquisition of these skills. METHODS: In this cross-sectional study, we determined the preferred sources/methods for health information among youths with chronic conditions and their relationship to health care transition readiness (STARx Questionnaire), self-efficacy (Iannotti's Diabetes Management Self-efficacy Scale), and medication adherence (Morisky Medication Adherence Scale). Youths with various chronic health conditions attending Victory Junction, a therapeutic camp, were invited to complete these online surveys. RESULTS: A total of 160 youths with different chronic conditions from multiple institutions, ages 6 to 16 years participated. Most commonly preferred sources of medical information were family/parents (n=122, 76.3%) and health care providers (n=88, 55.0%). Youths who favored family/parents had the highest medication adherence rates. In turn, youths who favored health care providers over other sources, scored highest on self-efficacy and transition readiness of all groups. CONCLUSION: Our novel findings represent important areas of intervention to improve transition readiness, self-efficacy, and medication adherence. Ascertaining the patients' preferred method of learning about the disease and its management is important in order to customize and enhance health care transition readiness, self-efficacy, and medication adherence. PMID- 26138375 TI - Brief Report: Adolescents' Reasons for Participating in a Health Care Transition Intervention Study. AB - PURPOSE: This study investigated the reasons adolescents with spina bifida consented or assented to participate in a randomized controlled prospective health care transition intervention study. METHODS: Sixty-five adolescents with spina bifida (SB), ages 14 to 18 years, who had previously participated in the Transition Preparation Training Program (TPT) study were recruited for the current study. A total of 26 consents/assents were obtained; a total of 25 questionnaires were returned (11 treatment; 14 control). Study findings were from a sample of 25 adolescents, aged 14 to 20 years who had participated in a randomized controlled prospective study entitled the Transition Preparation Training Program (TPT). Content analysis was used to code and analyze data. RESULTS: Study findings revealed adolescents indicated several reasons for choosing to participate in the research study. Major reasons cited for their participation were related to the desire to learn more about their condition and for altruistic purposes. Numerous reasons were offered by respondents as to why adolescents declined to participate in the research study; feelings of discomfort and issues of privacy were cited. Sixty-four percent of the respondents indicated the offer of a research incentive did not affect their decision to participate in the TPT study. Other findings are reported as to the use of research incentives and future recruitment recommendations. CONCLUSIONS: Youth shared a number of reasons and insights about recruitment strategies that may be helpful for future research efforts, especially those studies involving adolescents with special health care needs who participate in health care transition research. PMID- 26138376 TI - Solution NMR and molecular dynamics reveal a persistent alpha helix within the dynamic region of PsbQ from photosystem II of higher plants. AB - The extrinsic proteins of photosystem II of higher plants and green algae PsbO, PsbP, PsbQ, and PsbR are essential for stable oxygen production in the oxygen evolving center. In the available X-ray crystallographic structure of higher plant PsbQ residues S14-Y33 are missing. Building on the backbone NMR assignment of PsbQ, which includes this "missing link", we report the extended resonance assignment including side chain atoms. Based on nuclear Overhauser effect spectra a high resolution solution structure of PsbQ with a backbone RMSD of 0.81 A was obtained from torsion angle dynamics. Within the N-terminal residues 1-45 the solution structure deviates significantly from the X-ray crystallographic one, while the four-helix bundle core found previously is confirmed. A short alpha helix is observed in the solution structure at the location where a beta-strand had been proposed in the earlier crystallographic study. NMR relaxation data and unrestrained molecular dynamics simulations corroborate that the N-terminal region behaves as a flexible tail with a persistent short local helical secondary structure, while no indications of forming a beta-strand are found. PMID- 26138378 TI - Economic Burden of Undiagnosed Nonvalvular Atrial Fibrillation in the United States. AB - Atrial fibrillation (AF) may be clinically silent and therefore undiagnosed. To date, no estimates of the direct medical cost of undiagnosed AF exist. We estimated the United States (US) incremental cost burden of undiagnosed nonvalvular AF nationally using administrative claims data. To calculate the incremental costs of undiagnosed AF, we compared annual medical costs (in 2014 US Dollars) for patients with AF compared to propensity-matched controls and multiplied this by estimates of undiagnosed AF prevalence derived from the same data sources. The study population included US residents aged >=18 years with 24 months of continuous enrollment drawn from 2 large administrative claims databases. Mean per capita medical spending for patients with AF aged from 18 to 64 year was $38,861 (95% confidence interval [CI] $35,781 to $41,950) compared to $28,506 (95% CI $28,409 to $28,603) for similar patients without AF (incremental cost difference $10,355, p <0.001); total spending for patients aged >=65 years with AF was $25,322 (95% CI $25,049 to $25,595) compared to $21,706 (95% CI $21,563 to $21,849) for similar patients without AF (incremental cost difference $3,616, p <0.001). Using estimates of the US prevalence of undiagnosed AF (596,000) drawn from the same data, we estimated that the US incremental cost burden of undiagnosed nonvalvular AF is $3.1 billion (95% CI $2.7 to $3.7 billion). In conclusion, the direct medical costs for patients with undiagnosed AF are greater than patients with similar observable characteristics without AF and strategies to identify and treat patients with undiagnosed AF could lead to sizable reductions in stroke sequelae and associated costs. PMID- 26138377 TI - Prognostic Value of Stress Echocardiography in Patients With Low-Intermediate or High Short-Term (10 Years) Versus Low (<39%) or High (>=39%) Lifetime Predicted Risk of Cardiovascular Disease According to the American College of Cardiology/American Heart Association 2013 Cardiovascular Risk Calculator. AB - This study evaluates the prognostic value of stress echocardiography (Secho) in short-term (10 years) and lifetime atherosclerotic cardiovascular disease risk defined groups according to the American College of Cardiology/American Heart Association 2013 cardiovascular risk calculator. The ideal risk assessment and management of patients with low-to-intermediate or high short-term versus low (<39%) or high (>=39%) lifetime CV risk is unclear. The purpose of this study was to evaluate the prognostic value of Secho in short-term and lifetime CV risk defined groups. We evaluated 4,566 patients (60 +/- 13 years; 46% men) who underwent Secho (41% treadmill and 59% dobutamine) with low-intermediate short term (<20%) risk divided into low (<39%, n = 368) or high (>=39%, n = 661) lifetime CV risk and third group with high short-term risk (>=20%, n = 3,537). Follow-up (3.2 +/- 1.5 years) for nonfatal myocardial infarction (n = 102) and cardiac death (n = 140) were obtained. By univariate analysis, age (p <0.001) and >=3 new ischemic wall motion abnormalities (WMAs, p <0.001) were significant predictors of cardiac events. Cumulative survival in patients was significantly worse in patients with >=3 WMA versus <3 WMA in low-intermediate short-term and low (3.3% vs 0.3% per year, p <0.001) or high (2.0% vs 0% per year, p <0.001) lifetime risk and also in those with high short-term CV risk group (3.5% vs 1.0% per year, p <0.001). Multivariate Cox proportional hazards analysis identified >=3 new ischemic WMAs as the strongest predictor of cardiac events (hazard ratio 3.0, 95% confidence interval 2.3 to 3.9, p <0.001). In conclusion, Secho results (absence or presence of >=3 new ischemic segments) can further refine risk assessment in patients with low-intermediate or high short-term versus low or high lifetime cardiovascular risk. Event rate with normal Secho is low (<=1% per year) but higher in patients with high short-term CV risk by the American College of Cardiology/American Heart Association 2013 cardiovascular risk calculator. PMID- 26138379 TI - Hyperammonemia in Distal Renal Tubular Acidosis: A New Case and Review of the Literature. PMID- 26138380 TI - In vivo comparison of hard tissue regeneration with ovine mesenchymal stem cells processed with either the FICOLL method or the BMAC method. AB - INTRODUCTION: The aim of this work was to analyse the suitability of mesenchymal stem cell isolation by FICOLL density centrifugation and the closed bone marrow aspirate concentrate (BMAC) system for sinus augmentation with bovine bone mineral (BBM) in the sheep model. METHODS: 16 sheep underwent sinus augmentation with BBM and MSCs; they were divided between two groups with survival points of 8 and 16 weeks. For the FICOLL control arm three, and for the BMAC test arm, five augmentations were performed for each time point. The derived cell numbers were counted; a colony forming unit (CFU) assay was performed; the pluripotency of the MSCs was proved; histological and histomorphometrical analysis were performed. RESULTS: The approach of using BBM and MSCs in combination with fibrin adhesive was sufficient for new bone formation as the FICOLL experiment indicated. However, due to significantly lower cell numbers isolated using the BMAC in sheep, less new bone was formed in the test arm. CONCLUSIONS: The BMAC system is well suited for human MSC isolation but it needs to be optimized to fit sheep cell characteristics if it is to be used in this animal model. PMID- 26138381 TI - Differential expression of LOXL4 in normal and tumour tissue samples of laryngeal squamous cell carcinoma. AB - OBJECTIVE: Head and neck cancer is the sixth most common cancer in worldwide with an increasing incidence rate in recent years. LOXL4 is expressed in several tissues, and its expression has been shown to display a significant correlation with local lymph node metastasis. In this study, we aimed to explore the LOXL4 expression level in metastatic and non-metastatic LSCC tissues and to determine its prognostic significance. STUDY DESIGN: Basic science research study. SETTING: University hospital. PARTICIPANTS: A total of 40 patients were included in the study. MAIN OUTCOME MEASURE: LOXL4 expression status in metastatic, non metastatic LSCC and normal tissue samples was investigated by quantitative reverse-transcription PCR. RESULTS: We demonstrated that LOXL4 was significantly overexpressed in LSCC tumour tissue samples in comparison with the corresponding normal tissues (P < 0.001); however, no significant relationship has been found between LOXL4 expression and either the metastatic potential or the T classification of the specimens. CONCLUSIONS: Although expression of LOXL4 is not statistically associated with neck metastases, we showed that LOXL4 expression significantly increased in laryngeal cancer. PMID- 26138382 TI - Circulating full-length cytokeratin 18 for predicting prognosis of hepatitis B virus-related acute-on-chronic liver failure patients with lamivudine treatment. AB - AIM: The predictive value of circulating full-length cytokeratin 18 (M65) on prognosis of hepatitis B virus-related liver failure is still not well investigated. The aim of this study was to reveal the association between serum M65 levels and outcomes of hepatitis B virus-related acute-on-chronic liver failure, and to further clarify clinical significance of M65 in lamivudine treatment. METHODS: Ninety-six patients with hepatitis B virus-related acute-on chronic liver failure were recruited between January 2011 and December 2013, and 52 of them received lamivudine treatment. Blood were obtained from participants at admission, and M65 were determined by enzyme-linked immunosorbent assay. Other necessary data were collected from medical records. RESULTS: The liver failure patients were divided into high and low level groups according to the serum M65 levels. After 24-week follow up, survival incidences were significantly higher in the low level group than that in the high level group (odds ratio [OR] = 0.3, 95% confidence interval = 0.1-0.7). In addition, the survival incidences and albumin levels improved in the patients with lamivudine treatment compared with the patients without lamivudine treatment in the low level group (OR = 5.4, 95% CI = 1.1-26.0 and OR = 4.2, 95% CI = 1.3-13.2). A similar improvement was not observed in the high level group. CONCLUSION: The study suggested that the circulating M65 may serve as a relatively independent prognostic parameter for liver failure. If prospectively validated in further studies, M65 measurement may also be a useful method for optimizing antiviral therapy. PMID- 26138384 TI - Time will tell: resource continuity bolsters ecosystem services. AB - A common suggestion to support ecosystem services to agriculture provided by mobile organisms is to increase the amount of natural and seminatural habitat in the landscape. This might, however, be inefficient, and demands for agricultural products limit the feasibility of converting arable land into natural habitat. To develop more targeted means to promote ecosystem services, we need a solid understanding of the limitations to population growth for service-providing organisms. We propose a research agenda that identifies resource bottlenecks and interruptions over time to key beneficial organisms, emphasising their resulting population dynamics. Targeted measures that secure the continuity of resources throughout the life cycle of service-providing organisms are likely to effectively increase the stock, flow, and stability of ecosystem services. PMID- 26138385 TI - Plant domestication through an ecological lens. AB - Our understanding of domestication comes largely from archeology and genetics. Here, we advocate using current ecological theory and methodologies to provide novel insights into the causes and limitations of evolution under cultivation, as well as into the wider ecological impacts of domestication. We discuss the importance of natural selection under cultivation, that is, the forces promoting differences in Darwinian fitness between plants in crop populations and of constraints, that is, limitations of diverse nature that, given values for trait X, shorten the range of variation of trait Y, during the domestication process. Throughout this opinion paper, we highlight how ecology can yield insight into the effects of domestication on plant traits, on crop feedback over ecological processes, and on how species interactions develop in croplands. PMID- 26138383 TI - Targeting CGRP: A New Era for Migraine Treatment. AB - Migraine is a highly prevalent headache disease that typically affects patients during their most productive years. Despite significant progress in understanding the underlying pathophysiology of this disorder, its treatment so far continues to depend on drugs that, in their majority, were not specifically designed for this purpose. The neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack. It is not surprising that drugs designed to specifically block its action are gaining remarkable attention from researchers in the field with, at least so far, a safe risk profile. In this article, we highlight the evolution from older traditional treatments to the innovative CGRP target drugs that are revolutionizing the way to approach this debilitating neurological disease. We provide a brief introduction on pathophysiology of migraine and details on the characteristic, function, and localization of CGRP to then focus on CGRP receptor antagonists (CGRP-RAs) and CGRP monoclonal antibodies (CGRP mAbs). PMID- 26138386 TI - Error management in plant allocation to herbivore defense. AB - Herbivores can greatly reduce plant fitness. Error management theory (EMT) predicts the evolution of adaptive plant defensive strategies that err towards making less-costly errors so as to avoid making rare, costly errors. EMT provides a common framework for understanding observed levels of variation in plant defense among and within species. PMID- 26138387 TI - Risk factors for the rapid increase in risk of acute coronary events in patients with new-onset rheumatoid arthritis: a nested case-control study. AB - OBJECTIVE: To investigate risk factors for acute coronary syndrome (ACS) in patients with new-onset rheumatoid arthritis (RA). METHODS: We performed a nested case-control study of patients with incident RA included in the Epidemiological Investigation of RA study. Cases with ACS were identified using Swedish national health registers and matched with up to 5 controls without ACS, based on incidence density-based sampling. Information on potential exposures (clinical disease activity, serologic features, genetic markers, comorbidities, pharmacotherapies, and sick leave) was collected from medical charts and register based sources. RESULTS: We identified 138 cases and 624 controls. Smoking, history of myocardial infarction, and >50 days of sick leave the year following RA onset were associated with an increased risk of ACS. Area under the curve measurements of C-reactive protein level, erythrocyte sedimentation rate, Disease Activity Score in 28 joints (DAS28), and global health in the upper tertile during the first year and the complete followup period were both strongly associated with an increased risk of ACS. Treatment with disease-modifying antirheumatic drugs did not alter the ACS risk, nor did the presence of rheumatoid factor (RF) or shared epitope alleles, whereas high anti-citrullinated protein antibody (ACPA) levels were borderline significantly associated with ACS risk. CONCLUSION: In this study of risk factors for ACS in incident RA, clinical markers of inflammatory activity, disease activity, and total number of days of sick leave and disability pension during the first year following RA onset were identified as ACS risk factors. We found no association with RF, which was previously linked to cardiovascular disease risk in RA, but there was a borderline significant association with high ACPA levels. PMID- 26138388 TI - Neuritin reverses deficits in murine novel object associative recognition memory caused by exposure to extremely low-frequency (50 Hz) electromagnetic fields. AB - Animal studies have shown that electromagnetic field exposure may interfere with the activity of brain cells, thereby generating behavioral and cognitive disturbances. However, the underlying mechanisms and possible preventions are still unknown. In this study, we used a mouse model to examine the effects of exposure to extremely low-frequency (50 Hz) electromagnetic fields (ELF MFs) on a recognition memory task and morphological changes of hippocampal neurons. The data showed that ELF MFs exposure (1 mT, 12 h/day) induced a time-dependent deficit in novel object associative recognition memory and also decreased hippocampal dendritic spine density. This effect was observed without corresponding changes in spontaneous locomotor activity and was transient, which has only been seen after exposing mice to ELF MFs for 7-10 days. The over expression of hippocampal neuritin, an activity-dependent neurotrophic factor, using an adeno-associated virus (AAV) vector significantly increased the neuritin level and dendritic spine density. This increase was paralleled with ELF MFs exposure-induced deficits in recognition memory and reductions of dendritic spine density. Collectively, our study provides evidence for the association between ELF MFs exposure, impairment of recognition memory, and resulting changes in hippocampal dendritic spine density. Neuritin prevented this ELF MFs-exposure induced effect by increasing the hippocampal spine density. PMID- 26138389 TI - Evaluation of phytochemical content, antimicrobial, cytotoxic and antitumor activities of extract from Rumex hastatus D. Don roots. AB - BACKGROUND: Being a part of Chinese as well as ayurdic herbal system, roots of Rumex hastatus D. Don (RH) is highly medicinal, used to regulated blood pressure. It is also reported that the plant is diuretic, laxative, tonic, used against microbial skin diseases, bilious complaints and jaundice. The present study is conducted to evaluate phytochemical, antimicrobial, antitumor and cytotoxic activities of extract obtained from R. hastatus roots. METHODS: RH roots were powdered and extracted with methanol to get crude extract. Crude extract was further fractioned on the basis of increasing polarity, with n-hexane (HRR), chloroform (CRR), ethyl acetate (ERR), n-butanol (BRR) and residual aqueous fraction (ARR). Methanol extract and its derived fractions were subjected to phytochemical screening and assayed for antibacterial activities via agar well diffusion method. Antifungal activities were checked through agar tube dilution method whereas potato disc assay was employed for the determination of antitumor activity. On the other hand cytotoxic activities were conducted using brine shrimps procedures. RESULTS: The results obtained from phytochemical analysis indicate the presence of alkaloids, anthraquinones, flavonoids and saponins in all the fractions. Most of the plant fractions showed substantial antimicrobial activities, which is in accordance with the spacious use of tested plant samples in primary healthcare center. Fractions of R. hastatus roots for cytotoxicity were tested as an effective cytotoxic was found as BRR > MRR > CRR > ARR > ERR > HRR. Ranking order of fractions of R. hastatus roots for effective antitumor screening was found as MRR > BRR > ARR > CRR > ERR > HRR. CONCLUSIONS: These results showed that R. hastatus appeared as an important source for the discovery of new antimicrobial drugs and antitumor agents; verify its traditional uses and its exploitation as therapeutic agent. PMID- 26138390 TI - Enhanced contact endoscopy for the assessment of the neoangiogenetic changes in precancerous and cancerous lesions of the oral cavity and oropharynx. AB - Dysplasia and squamous cell carcinoma of the upper aerodigestive tract show significant neoangiogenesis appearing as subepithelial and epithelial microvascular irregularities that can be detected by Image-Enhanced Endoscopy such as Narrow Band Imaging and Storz Professional Image Enhancement System. In the present study, the most advanced endoscopic enhancement systems were coupled with Contact Endoscopy (Enhanced Contact Endoscopy). This original method improved the identification and the understanding of the neoangiogenetic changes of the chorion in 42 patients with leukoplakia, erythroplakia, and leuko erythroplakia of the oral cavity and oropharynx. The physiologic and pathologic mucosa was described in five obvious vascular patterns observed at Enhanced Contact Endoscopy ranging from normal to squamous cell carcinoma, passing through inflammation, hyperplasia, and dysplasia. Each vascular pattern was then compared to histology, showing that the microvascular architectural changes seen with Enhanced Contact Endoscopy are almost constant. Sensitivity, specificity, positive predictive value, and negative predictive value in the differentiation between healthy mucosa and inflammation versus pathologic hyperplasia, dysplasia, and carcinoma were, respectively, 96.6, 93.3, 98.2, 87.5, and 95.9 %. Sensitivity and specificity were 100 % in differentiation between non-malignant lesions versus squamous cell carcinoma. Our preliminary experience shows that accuracy of Image-Enhanced Endoscopy in the diagnosis of precancerous lesions and squamous cell carcinoma of the oral cavity and oropharynx can be increased if associated to Contact Endoscopy. PMID- 26138392 TI - [Middle lobe sindrome]. PMID- 26138391 TI - Caveolin 1 (Cav-1) and actin-related protein 2/3 complex, subunit 1B (ARPC1B) expressions as prognostic indicators for oral squamous cell carcinoma (OSCC). AB - Caveolin-1 (Cav-1) and Actin-Related Protein 2/3 Complex, Subunit 1B (ARPC1B) have been implicated in various human cancers, yet its role in tumorigenesis remains controversial. Therefore, this study aims to determine the protein expression of these two genes in oral squamous cell carcinomas (OSCCs) and to evaluate the clinical and prognostic impact of these genes in OSCC. Protein expressions of these two genes were determined by immunohistochemistry technique. The association between Cav-1 and ARPC1B with clinico-pathological parameters was evaluated by Chi-square test (or Fisher exact test where appropriate). Correlation between the protein expressions of these 2 genes with survival was analyzed using Kaplan-Meier and Cox regression models. Cav-1 and ARPC1B were found to be significantly over-expressed in OSCC compared to normal oral mucosa (p = 0.002 and p = 0.033, respectively). Low level of ARPC1B protein expression showed a significant correlation with lymph node metastasis (LNM) (p = 0.010) and advanced tumor staging (p = 0.003). Kaplan-Meier survival analyses demonstrated that patients with over-expression of Cav-1 protein were associated with poor prognosis (p = 0.030). Adjusted multivariate Cox regression model revealed that over-expression of Cav-1 remained as an independent significant prognostic factor for OSCC (HRR = 2.700, 95 % CI 1.013-7.198, p = 0.047). This study demonstrated that low-expression of ARPC1B is significantly associated with LNM and advanced tumor staging whereas high expression of Cav-1 can be a prognostic indicator for poor prognosis in OSCC patients. PMID- 26138393 TI - Tuning the catalytic properties of lipases immobilized on divinylsulfone activated agarose by altering its nanoenvironment. AB - Lipase from Thermomyces lanuginosus (TLL) and lipase B from Candida antarctica (CALB) have been immobilized on divinylsulfone (DVS) activated agarose beads at pH 10 for 72 h. Then, as a reaction end point, very different nucleophiles have been used to block the support and the effect of the nature of the blocking reagent has been analyzed on the features of the immobilized preparations. The blocking has generally positive effects on enzyme stability in both thermal and organic solvent inactivations. For example, CALB improved 7.5-fold the thermal stability after blocking with imidazole. The effect on enzyme activity was more variable, strongly depending on the substrate and the experimental conditions. Referring to CALB; using p-nitrophenyl butyrate (p-NPB) and methyl phenylacetate, activity always improved by the blocking step, whatever the blocking reagent, while with methyl mandelate or ethyl hexanoate not always the blocking presented a positive effect. Other example is TLL-DVS biocatalyst blocked with Cys. This was more than 8 times more active than the non-blocked preparation and become the most active versus p-NPB at pH 7, the least active versus methyl phenylacetate at pH 5 but the third one most active at pH 9, versus methyl mandelate presented lower activity than the unblocked preparation at pH 5 and versus ethyl hexanoate was the most active at all pH values. That way, enzyme specificity could be strongly altered by this blocking step. PMID- 26138394 TI - A rapid, sensitive, simple plate assay for detection of microbial alginate lyase activity. AB - Screening of microorganisms capable of producing alginate lyase enzyme is commonly carried out by investigating their abilities to grow on alginate containing solid media plates and occurrence of a clearance zone after flooding the plates with agents such as 10% (w/v) cetyl pyridinium chloride (CPC), which can form complexes with alginate. Although the CPC method is good, advantageous, and routinely used, the agar in the media interferes with the action of CPC, which makes judgment about clearance zones very difficult. In addition, this method takes a minimum of 30 min to obtain the zone of hydrolysis after flooding and the hydrolyzed area is not sharply discernible. An improved plate assay is reported herein for the detection of extracellular alginate lyase production by microorganisms. In this method, alginate-containing agar plates are flooded with Gram's iodine instead of CPC. Gram's iodine forms a bluish black complex with alginate but not with hydrolyzed alginate, giving sharp, distinct zones around the alginate lyase producing microbial colonies within 2-3 min. Gram's iodine method was found to be more effective than the CPC method in terms of visualization and measurement of zone size. The alginate-lyase-activity area indicated using the Gram's iodine method was found to be larger than that indicated by the CPC method. Both methods (CPC and Gram's iodine) showed the largest alginate lyase activity area for Saccharophagus degradans (ATCC 43961) followed by Microbulbifer mangrovi (KCTC 23483), Bacillus cereus (KF801505) and Paracoccus sp. LL1 (KP288668) grown on minimal sea salt medium. The rate of growth and metabolite production in alginate-containing minimal sea salt liquid medium, followed trends similar to that of the zone activity areas for the four bacteria under study. These results suggested that the assay developed in this study of Gram's iodine could be useful to predict the potential of microorganisms to produce alginate lyase. The method also worked well for screening and identification of alginate lyase producers and non-producers from environmental samples on common laboratory media. They did this by clearly showing the presence or absence of clearance zones around the microbial colonies grown. This new method is rapid, efficient, and could easily be performed for screening a large number of microbial cultures. This is the first report on the use of Gram's iodine for the detection of alginate lyase production by microorganisms using plate assay. PMID- 26138395 TI - Exchange of active site residues alters substrate specificity in extremely thermostable beta-glycosidase from Thermococcus kodakarensis KOD1. AB - beta-Glycosidase from Thermococcus kodakarensis KOD1 is a hyperthermophilic enzyme with beta-glucosidase, beta-mannosidase, beta-fucosidase and beta galactosidase activities. Sequence alignment with other beta-glycosidases from hyperthermophilic archaea showed two unique active site residues, Gln77 and Asp206. These residues were represented by Arg and Asp in all other hyperthermophilic beta-glycosidases. The two active site residues were mutated to Q77R, D206N and D206Q, to study the role of these unique active site residues in catalytic activity and to alter the substrate specificity to enhance its beta glucosidase activity. The secondary structure analysis of all the mutants showed no change in their structure and exhibited in similar conformation like wild-type as they all existed in dimer form in an SDS-PAGE under non-reducing conditions. Q77R and D206Q affected the catalytic activity of the enzyme whereas the D206N altered the catalytic turn-over rate for glucosidase and mannosidase activities with fucosidase activity remain unchanged. Gln77 is reported to interact with catalytic nucleophile and Asp206 with axial C2-hydroxyl group of substrates. Q77R might have made some changes in three dimensional structure due to its electrostatic effect and lost its catalytic activity. The extended side chains of D206Q is predicted to affect the substrate binding during catalysis. The high catalytic turn-over rate by D206N for beta-glucosidase activity makes it a useful enzyme in cellulose degradation at high temperatures. PMID- 26138396 TI - Protein disulfide isomerase homolog TrPDI2 contributing to cellobiohydrolase production in Trichoderma reesei. AB - The majority of the cysteine residues in the secreted proteins form disulfide bonds via protein disulfide isomerase (PDI)-mediated catalysis, stabilizing the enzyme activity. The role of PDI in cellulase production is speculative, as well as the possibility of PDI as a target for improving enzyme production efficiency of Trichoderma reesei, a widely used producer of enzyme for the production of lignocellulose-based biofuels and biochemicals. Here, we report that a PDI homolog, TrPDI2 in T. reesei exhibited a 36.94% and an 11.81% similarity to Aspergillus niger TIGA and T. reesei PDI1, respectively. The capability of TrPDI2 to recover the activity of reduced and denatured RNase by promoting refolding verified its protein disulfide isomerase activity. The overexpression of Trpdi2 increased the secretion and the activity of CBH1 at the early stage of cellulase induction. In addition, both the expression level and redox state of TrPDI2 responded to cellulase induction in T. reesei, providing sustainable oxidative power to ensure cellobiohydrolase maturation and production. The results suggest that TrPDI2 may contribute to cellobiohydrolase secretion by enhancing the capability of disulfide bond formation, which is essential for protein folding and maturation. PMID- 26138397 TI - Crystal structure of 1'-OH-carotenoid 3,4-desaturase from Nonlabens dokdonensis DSW-6. AB - The gamma-carotenoids, such as myxol and saproxanthin, have a high potential to be utilized in nutraceutical and pharmaceutical industries for their neuro protective and antioxidant effects. CrtD is involved in the production of gamma carotenoids by desaturating the C3'-C4' position of 1'-OH-gamma-carotenoid. We determined the crystal structure of CrtD from Nonlabens dokdonensis DSW-6 (NdCrtD), the first structure of CrtD family enzymes. The NdCrtD structure was composed of two distinct domains, an FAD-binding domain and a substrate-binding domain, and the substrate-binding domain can be divided into two subdomains, a Rossmann fold-like subdomain and a lid subdomain. Although the FAD-binding domain showed a structure similar to canonical FAD-containing enzymes, the substrate binding domain exhibited a novel structure to constitute a long and hydrophobic tunnel with a length of ~40 A. The molecular docking-simulation reveals that the tunnel provides an appropriate substrate-binding site for the carotenoid such as 1'-OH-gamma-carotene with a length of ~35 A. We could predict residues related to recognize the 1'-hydroxyl group and to stabilize the hydrophobic end without hydroxyl group. Moreover, we suggest that the flexible entrance loop may undergo an open-closed formational change during the binding of the substrate. PMID- 26138398 TI - Enhanced lignocellulosic biomass hydrolysis by oxidative lytic polysaccharide monooxygenases (LPMOs) GH61 from Gloeophyllum trabeum. AB - Lignocellulose is a renewable resource that is extremely abundant, and the complete enzymatic hydrolysis of lignocellulose requires a cocktail containing a variety of enzyme groups that act synergistically. The hydrolysis efficiency can be improved by introducing glycoside hydrolase 61 (GH61), a new enzyme that belongs to the auxiliary activity family 9 (AA9). GH61was isolated from Gloeophyllum trabeum and cleaves the glycosidic bonds on the cellulose surface via oxidation of various carbons. In this study, we investigated the properties of GH61. GtGH61 alone did not exhibit any notable activity, but the synergistic activity of GtGH61 with xylanase (GtXyl10G) or cellulase (GtCel5B) showed efficient bioconversion rates of 56 and 174% in pretreated kenaf (Hibiscus cannabinus L.) and oak (Quercus spp.), respectively. Furthermore, the GtGH61 activity was strongly accelerated in the presence of cobalt Co(2+). Enzyme cocktails (GtXyl10G, GtCel5B, and GtGH61) increased the amount of sugar released by 7 and 6% for pretreated oak and kenaf, respectively, and the addition of Co(2+) stimulated bioconversion by 12 and 11% in pretreated oak and kenaf, respectively. PMID- 26138399 TI - Kinetic characterization of a novel endo-beta-N-acetylglucosaminidase on concentrated bovine colostrum whey to release bioactive glycans. AB - EndoBI-1 is a recently isolated endo-beta-N-acetylglucosaminidase, which cleaves the N-N'-diacetyl chitobiose moiety found in the N-glycan core of high mannose, hybrid and complex N-glycans. These N-glycans have selective prebiotic activity for a key infant gut microbe, Bifidobacterium longum subsp. infantis. The broad specificity of EndoBI-1 suggests the enzyme may be useful for many applications, particularly for deglycosylating milk glycoproteins in dairy processing. To facilitate its commercial use, we determined kinetic parameters for EndoBI-1 on the model substrates ribonuclease B and bovine lactoferrin, as well as on concentrated bovine colostrum whey. Km values ranging from 0.25 to 0.49, 0.43 to 1.00 and 0.90 to 3.18 mg/mL and Vmax values ranging from 3.5*10(-3) to 5.09*10( 3), 4.5*10(-3) to 7.75*10(-3) and 1.9*10(-2)to 5.2*10(-2) mg/mL*min were determined for ribonuclease B, lactoferrin and whey, respectively. In general, EndoBI-1 showed the highest apparent affinity for ribonuclease B, while the maximum reaction rate was the highest for concentrated whey. EndoBI-1-released N glycans were quantified by a phenol-sulphuric total carbohydrate assay and the resultant N-glycan structures monitored by nano-LC-Chip-Q-TOF MS. The kinetic parameters and structural characterization of glycans released suggest EndoBI-1 can facilitate large-scale release of complex, bioactive glycans from a variety of glycoprotein substrates. Moreover, these results suggest that whey, often considered as a waste product, can be used effectively as a source of prebiotic N glycans. PMID- 26138400 TI - Enhancement of the thermostability of Streptomyces kathirae SC-1 tyrosinase by rational design and empirical mutation. AB - This study aimed to improve the thermostability of a newly cloned tyrosinase from Streptomyces kathirae SC-1. The POPMuSiC algorithm was applied to predict the folding free energy change (DeltaDG) of amino acid substitution. Site-directed mutagenesis was used to construct mutants (Q7K, G234P, and Q7K/G234P), and the mutant, and wild-type enzymes were expressed in Escherichia coli (DE3). Compared to the wild-type tyrosinase, all three mutant enzymes showed improved thermal properties. The mutant with combined substitution (Q7K/G234P) showed the most pronounced shifts in temperature optima, about 10 degrees C upward, and the half life for thermal inactivation at 60 degrees C, and melting temperatures were increased by 3 times and approximately 10 degrees C, respectively. Finally, the mechanisms responsible for the increased thermostability were analyzed through comparative analysis of structure models. The structure-based rational design strategies in this study may also provide further insight into the thermostability of other industrial enzymes and suggest further potential industrial applications. PMID- 26138401 TI - Characterization of bioactive recombinant antimicrobial peptide parasin I fused with human lysozyme expressed in the yeast Pichia pastoris system. AB - Parasin I (PI) is a 19 amino acid peptide with potent antimicrobial activities against a broad spectrum of microorganisms and is a good candidate for development as a novel antimicrobial agent. The objective of this study was to express and characterize a codon optimized parasin I peptide fused with human lysozyme (hLY). A 513 bp cDNA fragment encoding the mature hLY protein and parasin I peptide was designed and synthesized according to the codon bias of Pichia pastoris. A 4*Gly flexible amino acid linker with an enterokinase cleavage (DDDDK) was designed to link the PI to the C-terminal of hLY. The codon optimized recombinant hLY-PI was cloned into the pPICZalphaA vector and expressed in P. pastoris. The over-expressed extracellular rehLY-PI was purified using Ni sepharose affinity column and exhibited a molecular mass of approximately 18 kDa. After digested with enterokinase the rehLY-PI protein release its corresponding rehLY and rePI, with molecular mass of 16 kDa and 2 kDa, respectively, on Tricine SDS-PAGE. The released rehLY exhibited similar lytical activity against Micrococcus lysodeikticus to its commercial hLY. The digested rehLY-PI product exhibited antimicrobial activities against Bacillus subtilis, Staphylococcus aureus and Escherichia coli, and synergism has been found between the released rePI and rehLY. In conclusion, we successfully optimized a rehLY-PI fusion protein encoding gene and over-expressed the rehLY-PI in P. pastoris. The recombination protein digested with enterokinase released functional hLY and antimicrobial parasin I, which demonstrates a potential for future use as an animal feed additive to partly replace antibiotic. PMID- 26138402 TI - Cloning and characterization of a NADH-dependent aldo-keto reductase from a newly isolated Kluyveromyces lactis XP1461. AB - An aldo-keto reductase gene (klakr) from Kluyveromyces lactis XP1461 was cloned and heterologously expressed in Escherichia coli. The aldo-keto reductase KlAKR was purified and found to be NADH-dependent with a molecular weight of approximately 36 kDa. It is active and stable at 30 degrees C and pH 7.0. The maximal reaction rate (vmax), apparent Michaelis-Menten constant (Km) for NADH and t-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate (1a) and catalytic number (kcat) were calculated as 7.63 U mg(-1), 0.204 mM, 4.42 mM and 697.4 min(-1), respectively. Moreover, the KlAKR has broad substrate specificity to a range of aldehydes, ketones and keto-esters, producing chiral alcohol with e.e. or d.e. >99% for the majority of test substrates. PMID- 26138403 TI - How People with Depression Receive and Perceive Mental Illness Information: Findings from the Australian National Survey of Mental Health and Wellbeing. AB - Despite the recognised importance of accurate mental illness information in help seeking and improving recovery, little is known about the dissemination of such information to people with depression. With a view to informing effective communication to those most in need, we explored the extent to which mental illness information is received by people with depression, its perceived helpfulness and we characterise those who do not receive such information. Using data from the Australian National Survey of Mental Health and Wellbeing we observed that mental illness information was received by 54.7 % of those with depression. Most (76.7 %) found it helpful. Pamphlets were the most frequently cited source of information. People who did not receive information were less educated, unlikely to have accessed mental health services and unlikely to believe they had mental health needs. Targeted information campaigns which shape perceptions of need in relation to depression have the potential to reduce the resultant disease burden. PMID- 26138404 TI - Bacterial metabolism in immediate response to nutritional perturbation with temporal and network view of metabolites. AB - In this study, the initial propagation of metabolic perturbation in Escherichia coli was visualized to understand the dynamic characteristics of the metabolic pathways without the association of transcription alterations. E. coli cells were exposed to the sudden relief of glucose starvation, and time-dependent variances in metabolite balances were traced in the second scale. The acquired time-course data were represented by structural variations of the metabolite-metabolite correlation network. The initial correlation structure was altered immediately by the glucose pulse, followed by further structural variations within a few minutes. It was demonstrated that one metabolite temporally correlated with distinct metabolites with different timings, and such a behavior could imply a regulatory role for the metabolite in the metabolic network. Centrality analysis of the networks and partial correlation analysis indicated that preparation for growth and oxidative stress could be coupled as a structural property of the metabolic pathways. PMID- 26138405 TI - Can plasmonic Al nanoparticles improve absorption in triple junction solar cells? AB - Plasmonic nanoparticles located on the illuminated surface of a solar cell can perform the function of an antireflection layer, as well as a scattering layer, facilitating light-trapping. Al nanoparticles have recently been proposed to aid photocurrent enhancements in GaAs photodiodes in the wavelength region of 400-900 nm by mitigating any parasitic absorption losses. Because this spectral region corresponds to the top and middle sub-cell of a typical GaInP/GaInAs/Ge triple junction solar cell, in this work, we investigated the potential of similar periodic Al nanoparticles placed on top of a thin SiO2 spacer layer that can also serve as an antireflection coating at larger thicknesses. The particle period, diameter and the thickness of the oxide layers were optimised for the sub-cells using simulations to achieve the lowest reflection and maximum external quantum efficiencies. Our results highlight the importance of proper reference comparison, and unlike previously published results, raise doubts regarding the effectiveness of Al plasmonic nanoparticles as a suitable front-side scattering medium for broadband efficiency enhancements when compared to standard single layer antireflection coatings. However, by embedding the nanoparticles within the dielectric layer, they have the potential to perform better than an antireflection layer and provide enhanced response from both the sub-cells. PMID- 26138407 TI - A retrospective analysis of pediatric patients with lichen sclerosus treated with a standard protocol of class I topical corticosteroid and topical calcineurin inhibitor. AB - BACKGROUND: Lichen sclerosus (LS) is a chronic, inflammatory condition of the skin, affecting primarily the anogenital region potentially leading to changes in vaginal architecture and vulvar squamous cell carcinoma. Current recommended treatment for LS is high-potency corticosteroids. Calcineurin inhibitors may also have a role. OBJECTIVE: The objective of this study is to introduce a treatment regimen involving clobetasol to induce remission, then tacrolimus to maintain remission in pediatric females with LS. METHODS: As a retrospective case series, we report 14 pediatric females between 2 and 10 years of age with LS treated with clobetasol 0.05% topical ointment and systematically bridged to tacrolimus 0.1% topical ointment. For each patient, gender, age at disease onset, and clinical symptoms and features were noted. Time in weeks to 75% clearance and to complete clearance were recorded. RESULTS: Thirteen patients showed complete clearance. One patient showed significant clearance of the disease. The time to complete clearance averaged 43.1 weeks, with a range of 4-156 weeks. CONCLUSIONS: The use clobetasol to induce remission and tacrolimus to maintain remission can be used to treat LS in pediatric females. This regimen may minimize side effects associated with long-term, high-potency corticosteroid use and reduce the risk of changes to genital architecture secondary to LS. PMID- 26138406 TI - A multicenter, non-interventional study to evaluate patient-reported experiences of living with psoriasis. AB - BACKGROUND: Moderate to severe plaque psoriasis (with or without psoriatic arthritis) places significant burden on patients' lives. OBJECTIVE: Explore and document patients' experiences of living with psoriasis, including symptoms, treatments, impact on daily lives and patient-reported functioning. METHODS: In a US-based, non-interventional study, narrative interviews were conducted at baseline and again within 16 weeks. In interviews, patients with moderate to severe psoriasis indicated symptoms, ranked symptoms according to level of bother and indicated areas of their lives affected by psoriasis. Transcripts of interviews were coded for themes. Measurements of psoriasis severity including BSA, PGA and PASI were recorded. RESULTS: Symptoms reported most frequently included flaking/scaling (non-scalp areas), itching/scratching and rash, while the most bothersome symptoms were itching/scratching, flaking/scaling (non-scalp areas) and skin pain. Frequently reported impact areas were social and emotional. CONCLUSION: Broad-reaching interviews with patients with psoriasis show that these patients suffer in many aspects of their lives and in ways not indicated by typical psoriasis severity measures. Patients with psoriatic arthritis reported symptoms and disease-related complications at higher rates than those without arthritis. Physicians' explorations of the effect of psoriasis on patients' life events could aid in managing these patients. PMID- 26138408 TI - A Case Report of a Direct Catheterization of Tunneled Cuffed Catheter via Superior Vena Cava: A Choice after Vascular Access Exhaustion. AB - PURPOSE: To establish a new way for long-term vascular access for dialysis patient with vascular access exhaustion. MATERIALS AND METHODS: A patient with diabetes was found with edema of right arm and high venous pressure of AVF during hemodialysis. Intervention operations were performed to establish a tunneled cuffed catheterization. RESULTS: Occlusion of innominate vein was confirmed by MDCTV. Puncture to superior vena cava was successful 0.5 cm below the lateral head of sternocleidomastoid muscle directly via the right neck area. CONCLUSION: Direct puncture via superior vena cava might be the last choice for catheter insertion site. choice for catheter insertion site. PMID- 26138409 TI - Synthesis of disulfide-based biodegradable bridged silsesquioxane nanoparticles for two-photon imaging and therapy of cancer cells. AB - Biodegradable bridged silsesquioxane (BS) nanomaterials for two-photon-excited (TPE) imaging and therapy of breast cancer cells were described. A versatile synthesis was developed to design monodisperse tetra-alkoxysilylated diamino diphenylbutadiene or Zn-porphyrin-based nanospheres of 30 to 50 nm. PMID- 26138410 TI - First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild type cultivar. AB - BACKGROUND: Genetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals. METHODS: We performed oral food challenges in 21 apple-allergic individuals with Elstar apples which had undergone gene silencing of the major allergen of apple, Mal d 1, by RNA interference. Downregulation of Mal d 1 gene expression in the apples was verified by qRT-PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild-type Elstar using a visual analogue scale (VAS). RESULTS: Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 gene mRNA levels which were extensively downregulated, that is only 0.1-16.4% (e-DR1) and 0.2-9.9% (e-DR2) of those of the wild-type Elstar, respectively. Challenges with these downregulated apple lines produced significantly less intense maximal symptoms to the first dose (Vmax1) than with Elstar (Vmax1 Elstar 3.0 mm vs 0.0 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2 mm vs 0.2 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043). Only one subject (5%) remained symptom free when challenged with the Elstar apple, whereas 43% did so with e-DR1 and 63% with e-DR2. CONCLUSION: These data show that mRNA silencing of Mal d 1 results in a marked reduction of Mal d 1 gene expression in the fruit and reduction of symptoms when these apples are ingested by allergic subjects. Approximately half of the subjects developed no symptoms whatsoever, and virtually all subjects wished to consume the apple again in the future. PMID- 26138412 TI - Cytotoxic, Antiproliferative and Apoptotic Effects of New Benzimidazole Derivatives on A549 Lung Carcinoma and C6 Glioma Cell Lines. AB - Benzimidazole ring is a versatile structure which has been extensively utilized in medicinal chemistry. Since we are working on 1,2-disubstutited benzimidazoles, we have reported new antitumor active derivatives. As a continuation to our previous work, we have synthesized a new series of 1-(2-aryl-2-oxoethyl)-2 [(N,Ndimethylamino/pyrrolidinyl/piperidinyl)thiocarbamoyl] benzimidazole derivatives. Anticancer activity of the compounds was evaluated using MTT assay, BrdU assay and flow cytometric analysis on A549 human lung carcinoma and C6 rat glioma cell lines. Compounds bearing dimethylamino moiety exhibited higher antitumor activity. PMID- 26138411 TI - Choice of Human-Computer Interaction Mode in Stroke Rehabilitation. AB - BACKGROUND AND OBJECTIVE: Advances in technology are providing new forms of human computer interaction. The current study examined one form of human-computer interaction, augmented reality (AR), whereby subjects train in the real-world workspace with virtual objects projected by the computer. Motor performances were compared with those obtained while subjects used a traditional human-computer interaction, that is, a personal computer (PC) with a mouse. METHODS: Patients used goal-directed arm movements to play AR and PC versions of the Fruit Ninja video game. The 2 versions required the same arm movements to control the game but had different cognitive demands. With AR, the game was projected onto the desktop, where subjects viewed the game plus their arm movements simultaneously, in the same visual coordinate space. In the PC version, subjects used the same arm movements but viewed the game by looking up at a computer monitor. RESULTS: Among 18 patients with chronic hemiparesis after stroke, the AR game was associated with 21% higher game scores (P = .0001), 19% faster reaching times (P = .0001), and 15% less movement variability (P = .0068), as compared to the PC game. Correlations between game score and arm motor status were stronger with the AR version. CONCLUSIONS: Motor performances during the AR game were superior to those during the PC game. This result is due in part to the greater cognitive demands imposed by the PC game, a feature problematic for some patients but clinically useful for others. Mode of human-computer interface influences rehabilitation therapy demands and can be individualized for patients. PMID- 26138413 TI - [To further improve the expertise and management level of mechanical ventilation]. PMID- 26138414 TI - [An analysis of prognostic factors in patients suffering from acute lung injury/acute respiratory distress syndrome complicated with Yangming Fushi syndrome: a report of 206 cases from multiple centers]. AB - OBJECTIVE: To investigate the risk factors of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) complicated with Yangming Fushi syndrome. METHODS: A prospective study was conducted. From August 2009 to July 2013, 206 patients with Yangming Fushi syndrome combined with ALI/ARDS were enrolled in the intensive care units (ICUs) of the following five hospitals: Tianjin Nankai Hospital, Dongzhimen Hospital Affiliated to Beijing Traditional Chinese Medicine University, General Hospital of Tianjin Medical University, the First Affiliated Hospital of Dalian Medical University, and Wuxi Third People's Hospital in Jiangsu Province. According to the mortality occurring in ICU, the patients were divided into death group and survival group. The gender, age, acute physiology and chronic health evaluation II (APACHEII) score within the first 24 hours after admission, the length of invasive mechanical ventilation, usage of vasoactive agents, ratio of operative intervention, the length of stay in ICU, application of continuous renal replacement therapy (CRRT), amount of blood transfusion, the level of C-reactive protein (CRP), lactulose/mannitol (L/M) ratio, the number of organs with dysfunction, oxygenation index (PaO2/FiO2), levels of lactate and serum creatinine (SCr) of both groups were recorded. Logistic regression analysis was used to look for the independent risk factors of death of patients. RESULTS: There were 124 cases with severe acute pancreatitis (SAP), which was the most common disease with manifestation of Yangming Fushi syndrome combined with ALI/ARDS, accounting for 60.19% of all the patients. During the period of hospitalization in ICU, 171 patients survived and 35 died, and the mortality rate was 16.99%. The risk factors of the two groups were analyzed by variable analysis, and it was shown that compared with those in survival group, the age (years: 57.26+/-16.23 vs. 48.07+/-13.48, t=3.544, P=0.000), APACHEII score (20.83+/-9.73 vs. 12.61+/-6.63, t=4.777, P=0.000), the length of invasive mechanical ventilation (days: 10.97+/-7.71 vs. 6.91+/-2.48, t=2.555, P=0.015) and the number of dysfunction organs (3.11+/-1.21 vs. 1.60+/ 1.34, t=6.222, P=0.000) in death group were significantly higher. The level of PaO2/FiO2 [mmHg (1 mmHg=0.133 kPa): 218.56+/-64.90 vs. 244.58+/-85.10, t=-2.024, P=0.044] in the death group was significantly lower than that of the survival group, while the length of ICU stay (days: 14.33+/-10.81 vs. 9.11+/-7.37, t=2.600, P=0.010), the usage rates of CRRT [28.57% (10/35) vs. 15.20% (26/171), chi2=3.968, P=0.046], vasoactive agents [28.57% (10/35) vs. 12.28% (21/171), chi2=6.511, P=0.011], and blood transfusion ratio [42.86% (15/35) vs. 23.39% (40/171), chi2=7.042, P=0.008] were all obviously higher in the death group than those in the survival group. There were no statistically significant differences in gender, number of operation, the levels of CRP, L/M ratio, lactate and SCr between the two groups (all P>0.05). Multivariate logistic regression analysis showed that age [ odds ratio (OR)=0.938, 95% confidence interval (95%CI)=0.898 0.980, P=0.004], APACHE II score (OR=0.914, 95%CI=0.839-0.996, P=0.041), the number of dysfunction organs>=3 (OR=0.223, 95%CI=0.066-0.754, P=0.016), and the level of PaO2/FiO2 (OR=0.990, 95%CI=0.982-0.998, P=0.015) were independent risk factors for mortality. CONCLUSIONS: The age, APACHE II score, number of dysfunction organs>=3 and the level of PaO2/FiO2 are of significance in predicting the prognosis of patients with Yangming Fushi syndrome combined with ALI/ARDS. Patients with risk factors of high mortality should be more carefully monitored and treated aggressively. PMID- 26138415 TI - [The effects of high frequency oscillation ventilation on patients with acute respiratory distress syndrome: a Meta-analysis and sequential analysis of trial]. AB - OBJECTIVE: To evaluate the effect of high frequency oscillation ventilation (HFOV) vs. conventional mechanical ventilation (CV) on the treatment and prognosis of adult patients with acute respiratory distress syndrome (ARDS). METHODS: Published articles concerning randomized controlled trials (RCTs) about the effect of HFOV vs. CV on the prognosis of adult patients with ARDS published before May 2014 were retrieved from PubMed, EMBase, Cochrane central registry of controlled trials, CNKI and Wanfang Data. The mortality and data of physiological parameters were analyzed with STATA 12.0, and the mortality rate was also analyzed by trial sequential analysis with TSA 0.9, and the line chart was drawn with Microsoft Office Excel 2003. RESULTS: Seven trials with 1,731 patients met the criteria, all of them recorded the physiological parameters data, and mortality rate was mentioned in 6 trials (1,705 patients). Compared with CV, HFOV did not show any statistically significant beneficial effects on mortality [relative risk (RR)=0.93, 95% confidence interval (95%CI)=0.70-1.24, P=0.63], and other clinical outcomes, including survival without mechanical ventilation (RR=1.05, 95%CI=0.72-1.54, P=0.80), survival on mechanical ventilation (RR=1.23, 95%CI=0.65-2.35, P=0.52), or treatment failure (RR=0.89, 95%CI=0.50-1.56, P=0.67). The risk factors of adverse events including hypotension (RR=0.89, 95%CI=0.07-10.99, P=0.93), acidosis (RR=1.05, 95%CI=0.43-2.56, P=0.91), and air leakage from ventilator (RR=0.74, 95%CI=0.31-1.80, P=0.51) were similar. But the physiologic parameters of patients and parameters of ventilator in HFOV group, including oxygenation index, positive end-expiratory pressure, tidal volume, mean airway pressure, arterial pH, partial pressure of arterial carbon dioxide, fraction of inspired oxygen, ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, were better than those in the CV group. Methods adapted from formal interim monitoring boundaries applied to cumulative Meta analysis showed that the evidence failed by a considerable degree to meet the standards for forgoing studies, and the necessary sample was 3 874 patients. Trial sequential analysis also showed that the accumulated Z-score did not cross the traditional boundary (P=0.05) and interim monitoring boundaries. This result indicated that there was no significant difference between CV and HFOV on mortality before the number of needed sample reached (3,874 cases). We could not get a definitive conclusion with current evidences. CONCLUSIONS: Compared with CV, the use of HFOV in ARDS was not associated with a significant reduction in mortality. But the physiologic parameters of patients in HFOV group were better than those in the CV group. More RCTs are needed to draw a definitive conclusion. PMID- 26138416 TI - [Analysis of the risk factors of acute respiratory distress syndrome of Berlin new definition in patients with sepsis in emergency department]. AB - OBJECTIVE: To discuss the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis in emergency department. METHODS: 312 patients with sepsis admitted to Department of Emergency of China Medical University Affiliated First Hospital were retrospectively analyzed, and they were divided into two groups according to development of ARDS, which was defined according to the Berlin new definition. The age, gender, vital signs, laboratory results, underlying disease, the mortality in emergency department sepsis (MEDS) score and lung injury prediction score (LIPS) were collected. Univariate analysis was done for each parameter. Statistical significance results were evaluated by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the parameter for ARDS. RESULTS: The incidence of sepsis-related ARDS was 11.2% (35/312). Within 35 cases of ARDS, there were 10 cases of mild ARDS, 18 cases of moderate ARDS, and 7 cases of severe ARDS. Univariate analysis showed that age (t=-2.134, P=0.035), oxygenation index (t=-4.245, P=0.001), arterial lactate (Lac, t=6.245, P<0.001), drugs for vascular diseases (chi2=4.261, P=0.026), shock (chi2=4.386, P=0.021), MEDS (t=4.021, P=0.045), LIPS (t=5.569, P<0.001), lung infections (chi2=4.289, P=0.025), and mechanical ventilation (chi2=6.245, P=0.001) were related to ARDS. The incidence of ARDS was different in different levels of Lac, which was 5.00% (3/16) at low level of Lac (<2.0 mmol/L), 9.46% (14/148) at middle level of Lac (2.0-3.9 mmol/L) and 17.31% (18/104) at high level of Lac (>=4.0 mmol/L). It was shown by multivariate logistic regression analysis that LIPS [ odds ratio (OR)=5.124, 95% confidence interval (95%CI)=3.642-10.153, P=0.002], Lac (OR=18.180, 95%CI=7.677-32.989, P<0.001) were independent risk factors for ARDS. It was shown by area under ROC (AUC) that the predictive value of LIPS and Lac in ARDS occurrence was significant. AUC of LIPS was 0.725, the cut-off value was 7, when LIPS>=7, the sensitivity was 71.0%, specificity was 75.6%. AUC of Lac was 0.793, the cut-off value was 4.2 mmol/L, when Lac>=4.2 mmol/L, the sensitivity was 72.1%, and specificity was 81.9%. CONCLUSIONS: LIPS and Lac are independent risk factors of ARDS in patients with sepsis in emergency department, which may be a reference for the early clinical diagnosis of ARDS. PMID- 26138417 TI - [Clinical feature of severe hand, foot and mouth disease with acute pulmonary edema in pediatric patients]. AB - OBJECTIVE: To explore the clinical feature of severe hand, foot and mouth disease (HFMD) in pediatric patients, and to observe the hemodynamic changes in those with acute pulmonary edema. METHODS: A prospective observation study was conducted. Thirty-five severe HFMD pediatric patients with acute pulmonary edema admitted to the intensive care unit (ICU) and Department of Pediatric of First People's Hospital of Foshan from May 2008 to September 2014 were enrolled. The clinical features were thoroughly investigated. Hemodynamic data were monitored by pulse-indicated continuous cardiac output (PiCCO) in 5 cases, and the changes in PiCCO parameters were observed at ICU admission (0 hour), and 24, 48, 96 hours after treatment. RESULTS: Thirty-five patients who met the diagnostic standard of severe HFMD were enrolled, including 22 male and 13 female, aged from 7 months to 4 years. Six patients were younger than 1 year, 13 1-2 years, 12 2-3 years, and 4 patients 3-4 years old. The most common time of occurrence of pulmonary edema was 3-4 days after the onset of the disease. Fever and central nervous system symptoms were found in all the patients, and examination of the cerebral spinal fluid (CSF) revealed non-bacterial inflammatory changes. PiCCO results showed a tendency of lowering of heart rate (HR), systemic vascular resistance index (SVRI), and extravascular lung water index (EVLWI) after the treatment, and the values obtained at 96 hours were significantly lower than those at 0 hour [HR (bpm): 119.0+/-14.7 vs. 200.8+/-19.7, SVRI (kPa*s*L(-1)*m(-2)): 148.9+/-14.6 vs. 209.6+/-58.7, EVLWI (mL/kg): 10.5+/-1.9 vs. 34.8+/-10.8, P<0.05 or P<0.01], global end-diastolic volume index (GEDVI) was also gradually decreased without significant differences among all the time points, together with a tendency of increase in stroke volume index (SI) and cardiac index (CI). The values of the parameters at 96 hours were significantly higher than those at 0 hour [SI (mL/m2): 38.5+/-6.5 vs. 17.4+/-2.8, CI (mL*s(-1)*m(-2)): 75.0+/-8.0 vs. 55.5+/ 8.5, both P<0.01]. Left atrium was found to be enlarged, and left ventricular systolic function decreased in two patients by cardiac ultrasonic. Four out of 35 patients died, and functional disability of extremities was found in 1 patient. Other patients were cured and discharged without any sequelae. CONCLUSIONS: Severe HFMD complicated by acute pulmonary edema is a perilous condition in children, accompanied commonly by pathologic changes in central nervous system and systolic dysfunction of left ventricle. According to the results with PiCCO monitoring, HFMD patients suffering from acute pulmonary edema may be of cardiac origin in addition to neurogenic origin. PMID- 26138418 TI - [Research on the effect of protection against ventilator-induced lung injury via regulation of caveolin-1/heme oxygenase-1 signaling]. AB - OBJECTIVE: To determine whether the inhibition of caveolin-1 tyrosine residues 14 (Cav-1-Y14) phosphorylation with protein tyrosine kinase inhibitors (PP2) will upregulate heme oxygenase-1 (HO-1) activity to protect against ventilation induced lung injury in vivo of an animal model. METHODS: Fifty-four male Sprague Dawley (SD) rats were randomly divided into nine groups (each n=6). Group A served as normal control group, in which rats did not receive ventilation but tracheotomy. Groups B1 and B2 received lung protective ventilation respectively for 1 hour or 2 hours. Groups C1 and C2 received high tidal volume (40 mL/kg) ventilation for 1 hour or 2 hours, respectively. The group D1 or D2 also received high tidal volume ventilation for 1 hour or 2 hour respectively, but they were given PP2 1 hour before high tidal volume ventilation. The groups E1 and E2 also received high tidal volume ventilation respectively for 1 hour or 2 hours, but tyrosine kinase inhibitor PP2 and HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) were given to animals 18 hours before high tidal volume ventilation. All the animals were sacrificed after ventilation, and the specimens of lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Then the changes in pathology of lung tissue was observed, and diffuse alveolar damage scores (DAD) were calculated, myeloperoxidase (MPO) activity was measured by colorimetric analysis, lung wet/dry ratio (W/D) was estimated. The expressions of phosphorylated caveolin-1 (P-Cav-1-Y14), caveolin-1 (Cav-1) and HO-1 were determined by Western Blot. The expressions of high mobility group B1 (HMGB1) and advanced glycation end product receptor (RAGE) in lung tissues were assayed with immunohistochemistry staining. The levels of tumor necrosis factor-alpha(TNF alpha) in BALF were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: There was no significant difference in all the parameters between group A and groups B. Compared with group B1, DAD score, W/D ratio, the activity of MPO and the concentration of TNF-alpha in BALF in group C1 were significantly increased [ DAD score: 7.97+/-0.59 vs. 0.55+/-0.13, W/D ratio: 5.70+/-1.61 vs. 5.04+/-0.63, MPO (U/g): 1.82+/-0.14 vs. 0.77+/-0.26, TNF-alpha (ng/L): 370.10+/ 29.61 vs. 54.38+/-8.18, all P<0.05], and the injury in ventilation 2 hours group was more serious than that in ventilation 1 hour group. Compared with groups C, all the parameters in groups D were significantly decreased. The parameters in groups E were significantly higher than those in groups A, B, and D, but no significant difference was found as compared with groups C. Compared with groups B, the protein expressions of Cav-1 and P-Cav-1-Y14 (gray value) in groups C were significantly increased (1 hour: 1.49+/-0.02 vs. 1.26+/-0.13, 1.34+/-0.02 vs. 0.87+/-0.04; 2 hours: 1.58+/-0.02 vs. 1.27+/-0.27, 1.31+/-0.01 vs. 0.95+/-0.02, all P<0.05), and the expression of HO-1 protein (gray value) was significantly decreased (1 hour: 0.59+/-0.02 vs. 1.10+/-0.01, 2 hours: 0.49+/-0.01 vs. 1.20+/ 0.02, both P<0.05). No significant difference in Cav-1 protein expression between groups D as well as groups E and groups C. The protein expression of P-Cav-1-Y14 in groups D and E was significantly lower than that in groups C. The protein expression of HO-1 in groups D was significantly higher than that in groups C, but the phenomenon was not found in groups E as compared with groups C. Compared with group A, the positive expression of HMGB1 and RAGE in lung tissue in groups C and E was significantly increased, but no significant difference was found between groups B as well as groups D and group A. CONCLUSIONS: Cav-1-Y14 phosphorylation is the key factor for ventilator induced lung injury, which can not only lead to a decrease in vascular barrier function, but also inhibit the activity of HO-1 enzyme, thus further aggravates inflammatory injury of the lung as induced by mechanical ventilation. PMID- 26138419 TI - [The molecular mechanism of antiapoptosis of type II alveolar epithelial cell by microRNA-21-5p]. AB - OBJECTIVE: To study the effect of hydrogen peroxide (H2O2) in inducing apoptosis of type II alveolar epithelial cell (AECII) after overexpression by adenoviral transfection of micro RNA-21-5p (miR-21-5p), and to explore the mechanism of its anti-apoptosis. METHODS: Subculture AECII were randomly divided into four groups: normal control group (normal saline), H2O2 challenge group (0.5 mmol/L H2O2), miR 21-5p overexpression group (miR-21-5p adenovirus+0.5 mmol/L H2O2), miR-21-5p negative transfection group (adenovirus void+0.5 mmol/L H2O2). Transmission electron microscopy and flow cytometry were used to detect apoptotic morphology and early apoptotic rate. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of miR-21-5p in AECII, and Western Blot was used to detect the protein expressions of Bcl-2, Bax, and caspase-3 at the highest transfection efficiency at different time points (6, 12, 24, 48 hours). RESULTS: (1) AECII identification: fluorescence microscopy showed the presence of characteristic structure of AECII, i.e. microvilli and osmiophilic lamellar bodies. (2) Apoptotic morphology: transmission electron microscopy showed cytoplasmic retraction, chromatin condensation, margination, lack of cell surface microvilli, and emptying of osmiophilic lamellar bodies in AECII. (3) The expression of miR 21-5p in AECII: the highest transfection efficiency was found at 48 hours. The expression of miR-21-5p in miR-21-5p overexpression group was significantly higher than that of the normal control group, H2O2 challenge group and miR-21-5p negative transfection group (A value: 1.54+/-0.02 vs. 1.02+/-0.02, 0.56+/-0.03, 0.58+/-0.02, all P<0.05). (4) The rate of early apoptosis: compared with normal control group, the early apoptotic rates in H2O2 challenge group, miR-21-5p negative transfection group and miR-21-5p overexpression group were gradually elevated with the prolongation of injury time. The early apoptotic rate in miR-21 5p overexpression group was significantly lower than that of the H2O2 challenge group and miR-21-5p negative transfection group at all time points except 6 hours [12 hours: (10.73+/-2.80)% vs. (16.26+/-0.59)%, (16.04+/-0.70)%; 24 hours: (16.00+/-3.44)% vs. (23.29+/-2.78)%, (23.58+/-2.31)%; 48 hours: (31.30+/-3.55)% vs. (50.53+/-2.17)%, (49.41+/-1.97)%, all P<0.05]. There was no significant difference in early apoptotic rate between miR-21-5p negative transfection group and H2O2 challenge group at each time point. (5) Protein expression: the expressions of Bax and caspase-3 in miR-21-5p overexpression group were significantly lower than those of the H2O2 challenge group and miR-21-5p negative transfection group [Bax (A value): 0.07+/-0.01 vs. 0.18+/-0.01, 0.13+/-0.01; caspase-3 (A value): 0.07+/-0.01 vs. 0.23+/-0.01, 0.12+/-0.01, all P<0.05], and Bcl-2 protein expression was significantly higher than that of the H2O2 challenge group and miR-21-5p negative transfection group (A value: 0.26+/-0.01 vs. 0.06+/ 0.01, 0.10+/-0.01, both P<0.05). CONCLUSIONS: (1) miR-21-5p has the function of anti-apoptosis of AECII. (2) Adenoviral vector is a successful gene transfer vector when transfected with AECII. (3) The anti-apoptosis of AECII by miR-21-5p may be associated with reduced Bax and caspase-3 protein levels and raised expression levels of Bcl-2 protein. PMID- 26138420 TI - [The value of lung ultrasound score on evaluating clinical severity and prognosis in patients with acute respiratory distress syndrome]. AB - OBJECTIVE: To evaluate the value of lung ultrasound score (LUS) on assessing the severity and prognosis in patients with acute respiratory distress syndrome (ARDS), and to investigate its correlation with oxygenation index, acute physiology and chronic health evaluationII (APACHEII) score, sequential organ failure assessment (SOFA) score, and clinical pulmonary infection score (CPIS), and other traditional parameters. METHODS: A prospective double-blind cohort study was conducted. Sixty-two ARDS patients conformed to the Berlin diagnostic criteria admitted to intensive care unit (ICU) of Beijing Huaxin Hospital from October 2013 to December 2014 were enrolled, including 14 cases with mild, 18 moderate, and 30 severe ARDS; among them 37 cases were of ARDS with pulmonary origin, and 25 non-pulmonary ARDS; 35 patients survived, and 27 died. The clinical data and scores of all patients were recorded by one specialized observer, including baseline data, hemodynamic parameters, lactate, respiratory parameters, and APACHEII, SOFA and CPIS scores. Another observer of recording was responsible for the results of lung ultrasound, LUS, and echocardiogram. The correlation between LUS and oxygenation index as well as APACHEII, SOFA and CPIS scores was analyzed by bivariate correlation analysis. Receiver operator characteristic curve (ROC) was plotted, and the predictive value, sensitivity and specificity of mild ARDS, moderate ARDS, severe ARDS and mortality by LUS were calculated. RESULTS: LUS had a negative correlation with oxygenation index (r= 0.755, P<0.001), a good positive correlation with APACHEII (r=0.504, P<0.001), SOFA (r=0.461, P<0.001) and CPIS (r=0.571, P<0.001) was found. LUS in the pulmonary ARDS group had a positive correlation with CPIS (r=0.399, P<0.05), and a positive correlation was found in non-pulmonary ARDS group (r=0.350, P<0.05), which indicated that the correlation in pulmonary ARDS was more satisfactory than that in non-pulmonary ARDS. LUS in the pulmonary ARDS group was significantly higher than that in non-pulmonary ARDS group (22.1+/-4.9 vs. 11.3+/-2.1, t=11.667, P<0.001); LUS in mild, moderate, severe ARDS groups was 9.9+/-1.7, 14.0+/-1.4, 23.6+/-4.1. The predictive value for mild ARDS by LUS was 7.0, sensitivity of 87.0%, specificity of 89.0%; that for moderate ARDS was 11.0, sensitivity of 89.0%, specificity of 87.0%; that for severe ARDS was 8.0, sensitivity of 90.0%, specificity of 88.5%. LUS was 24.3+/-3.8 in the death group, and 12.7+/-2.9 in the survival group. Area under ROC curve (AUC) was calculated, and the patients with LUS>19.0 had a high mortality, sensitivity for predicting death was 84.0%, and specificity of 89.0%. CONCLUSIONS: Bedside LUS, which is simple and easily available, could evaluate the changes in pulmonary ventilation area of ARDS, and its degree of severity, and prognosis including prediction of mortality of the patients. PMID- 26138421 TI - [Effects of mechanical ventilation with different tidal volumes on coagulation/fibrinolysis in rabbits with acute respiratory distress syndrome]. AB - OBJECTIVE: To observe the effects of mechanical ventilation with different tidal volumes (VT) on coagulability and fibrinolytic characteristics in rabbits with acute respiratory distress syndrome (ARDS) induced by two-hits with oleic acid (OA) and lipopolysaccharide (LPS). METHODS: Forty healthy adult male rabbits were randomly divided into five groups (8 rabbits in each group): sham operation group, model group, low VT group (6 mL/kg), rontine VT group (10 mL/kg ), high VT group (15 mL/kg). ARDS model was reproduced by sequential injection of 0.1 mL/kg OA and 500 MUg/kg LPS via auricular vein, and the rabbits in sham operation group received normal saline in same volume. Mechanical ventilation was performed in different VT groups after model reproduction, and the end of the experiment was determined as 6 hours after LPS injection. Blood was collected from the carotid artery at 30 minutes and 360 minutes after LPS injection, with which arterial partial pressure of oxygen (PaO2) was determined, and oxygenation index was calculated. Internal jugular vein blood was collected at 5, 120, 240, and 360 minutes after LPS injection, and activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib) and antithrombin III (AT-III) were determined. The blood was collected at the end of the experiment, and then the rabbits were sacrificed, and serum levels of procollagen type III (PIIIP), plasminogen activator inhibitor-1 (PAI-1) as well as PIIIP level in lung tissue were determined. The wet/dry weight ratio (W/D) of lung tissues was calculated. RESULTS: Compared with sham operation group, oxygenation index at both 30 minutes and 360 minutes were significantly decreased in model group, while W/D ratio was significantly increased. PT and APTT at 5 minutes were significantly shortened followed by a gradual increase. Fib and AT-III showed no change at 5 minutes followed by a gradual decrease, while serum PAI-1 and PIIIP as well as PIIIP in lung tissue were significantly increased. There was no significant difference in oxygenation index between all VT groups and model group, with a tendency to increase in low VT group. W/D ratio in low VT group was the lowest (5.09+/-0.19), and it was significantly lower than that of the model group (6.02+/-0.27, P<0.01), while it was the highest in high VT group (6.27+/-0.32). PT and APTT in all VT groups were gradually prolonged, and Fib and AT-III were gradually decreased. PT and APTT in low VT group were significantly shorter than those in model group from 120 minutes on [PT (s): 120 minutes: 8.90+/-0.28 vs. 11.43+/ 0.28, 240 minutes: 9.18+/-0.21 vs. 11.99+/-0.50, 360 minutes: 9.25+/-0.15 vs. 12.49+/-0.29; APTT (s): 120 minutes: 69.09+/-3.91 vs. 76.08+/-4.21, 240 minutes: 67.53+/-2.14 vs. 79.71+/-2.25, 360 minutes: 66.95+/-1.13 vs. 83.21+/-4.01, all P<0.05], Fib (g/L) was significantly elevated (120 minutes: 3.80+/-0.09 vs. 3.38+/-0.15, 240 minutes: 3.91+/-0.05 vs. 2.47+/-0.16, 360 minutes: 4.06+/-0.13 vs. 2.39+/-0.16, all P<0.05), and no significant difference was found in AT-III. Serum contents of PAI-1 and PIIIP as well as PIIIP in lung tissue were significantly lowered [ serum PAI-1 (ng/L): 1.14+/-0.26 vs. 1.63+/-0.91, serum PIIIP (ng/L): 1.62+/-0.52 vs. 2.91+/-0.64, lung PIIIP (ng/L): 4.40+/-0.58 vs. 5.75+/-0.47, all P<0.01]. The change tendency of all parameters in routine VT group was lower than that in low VT group, PT at 120 minutes and 360 minutes, APTT at 240 minutes and 360 minutes was significantly shorter than that in model group, and Fib at 120 minutes and 240 minutes were significantly higher than those in model group (all P<0.05). No significant difference was found in AT-III, serum PAI-1 and PIIIP as well as lung PIIIP as compared with model group. PT and APTT at 360 minutes in high VT group were significantly longer than those in model group, Fib at 360 minutes was significantly lower than that in model group, and lung PIIIP was significantly higher than that in model group. CONCLUSIONS: There are some important changes in coagulability which changes from a hyper state into a hypo coagulate state, while fibrinolysis is inhibited during the pathological process of ARDS produced by two-hit of OA and LPS. Mechanical ventilation with low VT can obviously improve coagulability and fibrinolytic status, while ventilation with routine VT has little effect on coagulability and fibrinolytic status. Mechanical ventilation with high VT, however, will greatly deteriorate the coagulability and fibrinolytic function in ARDS. PMID- 26138422 TI - [The protective effects of transfected microRNA-146a on mice with sepsis-induced acute lung injury in vivo]. AB - OBJECTIVE: To investigate the protective effect of transfected microRNA-146a (miR 146a) on mice with sepsis-induced acute lung injury (ALI) in vivo. METHODS: Twenty-four healthy male BALB/C mice were randomly divided into sham group, sepsis group, transfection group and transfection control group, each n=6. Mice in transfection group were given miR-146a agomir loaded by in vivo-jetPEITM via airway before reproduction of model, and mice in transfection control group were given negative control loaded by in vivo-jetPEITM only via airway. The septic model was reproduced by cecal ligation and puncture (CLP) 12 hours after transfection , and the mice in the sham group underwent laparotomy and closure only without ligation and puncture of the cecum. The mice of each group were sacrificed at 24 hours post-operation. The expression of miR-146a in lung tissue was determined by real time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the quantity of tumor necrosis factor alpha (TNF-alpha) in the bronchial alveolar lavage fluid (BALF) was determined with enzyme-linked immunosorbent assay (ELISA). The wet/dry ratio of lung (W/D) was determined. The pathohistological changes in the lung were observed and scored. RESULTS: The expression of miR-146a showed a significant increase in sepsis group, transfection group and transfection control group, which were (3.56+/-0.43), (27.64+/-3.46) and (3.72+/-0.54) folds of that in sham group, respectively (P<0.05 or P<0.01). The miR-146a expression in transfection group was significantly increased compared with sepsis group and transfection control group (both P<0.01), but no statistical difference in the expression was found between sepsis group and transfection control group (P>0.05). Compared with the sham group, higher level of TNF-alpha in the BALF was found in the sepsis group, transfection group and transfection control group (ng/L: 511.65+/-43.47, 305.74+/ 34.76, 492.27+/-42.21 vs. 50.72+/-7.23, all P<0.01). The level of TNF-alpha in transfection group was significantly lower than that in sepsis group and transfection control group (both P<0.01). Compared with the sham group, the W/D ratio of lung in sepsis group, transfection group and transfection control group showed a significant increase (6.11+/-0.32, 5.02+/-0.29, 6.05+/-0.43 vs. 4.18+/ 0.10, all P<0.01). The W/D ratio of lung in transfection group was significantly lower than that of sepsis group and transfection control group (both P<0.01). The lung injury score of transfection group was significantly lower than that of sepsis group and transfection control group (6.12+/-0.75 vs. 10.53+/-1.52, 9.73+/ 1.08, both P<0.01). CONCLUSIONS: miR-146a agomir loaded by in vivo-jetPEITM instillation into airway was able to increase the expression of miR-146a in the lung tissue of septic mice. Up-regulation of miR-146a inhibit the release of the inflammatory cytokine TNF-alpha stimulated by sepsis, and alleviate inflammatory reaction and lung tissue injury in mice with sepsis-induced ALI. PMID- 26138423 TI - [An investigation of the efficacy of invasive-noninvasive sequential mechanical ventilation in senile patients with severe community-acquired pneumonia]. AB - OBJECTIVE: To investigate the efficacy of invasive-noninvasive sequential mechanical ventilation (MV) in senile patients with severe community-acquired pneumonia (CAP). METHODS: A prospective study was conducted. The patients with severe CAP aged >=75 years admitted to Department of Respiratory Intensive Care Unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from November 2012 to July 2014, with refusal to have tracheostomy, were enrolled. All patients meeting the diagnostic criteria of CAP and severe CAP were first admitted into the Department of Emergency, and they were found to need MV without absolute contraindication for noninvasive ventilation (NIV) in RICU. The patients were mechanically ventilated via endotracheal intubation (ETI), and they were randomly divided into invasive-noninvasive sequential MV group (sequential MV group) and conventional MV group. NIV was initiated immediately when patients matched the conditions for early extubation in the sequential MV group. Oxygen therapy (5 L/min) via a Venturi mask was provided when the indications of conventional extubation were met. The baseline data and clinical characteristics were recorded, the risk factors of death were analyzed by logistic regression analysis, and 60-day survival rate was analyzed by Kaplan-Meier curve. RESULTS: Ninety-one senile patients with severe CAP were enrolled, among them 28 patients died within 60 days, with a mortality rate of 30.77%. No significant difference in 60-day mortality was found between sequential MV group (n=44) and conventional MV group [n=47, 25.0% (11/44) vs. 36.2% (17/47), chi2=1.331, P=0.249]. In the sequential MV group, the incidence of ventilator-associated pneumonia (VAP) was significantly decreased [27.3% (12/44) vs. 55.3% (26/47), chi2=7.350, P=0.007], and the rate of ETI>=2 times was increased [59.1% (26/44) vs. 29.8% (14/47), chi2=5.095, P=0.024] as compared with conventional MV group. Compared with survival group, the patients in non-survival group showed a higher incidence of cerebrovascular disease (60.7% vs. 25.4%, P=0.002), higher acute physiology and chronic health evaluation II (APACHEII) score (26.46+/-2.59 vs. 24.41+/-2.47, P=0.001), British Thoracic Society confusion, uremia, respiratory rate, blood pressure, >=75 years (CURB-75 score, 4.00+/-0.47 vs. 3.68+/-0.53, P=0.013), a longer total duration of MV (days: 21.18+/-10.02 vs. 14.56+/-7.62, P=0.002), and a higher ratio of ETI>=2 times (53.6% vs. 33.3%, P<0.001). It was revealed by multivariate logistic regression analysis that ETI>=2 times and comorbidity of cerebrovascular infarction were independent predictors of a worse outcome in the senile patients [odds ratio (OR)=9.677, 95% confidence interval (95%CI)=3.075 30.457, P<0.001; OR=5.386, 95%CI=1.781-6.284, P=0.003]. It was showed by Kaplan Meir survival analysis that ETI times and concurrent cerebrovascular infarction imparted significant effects on the 60-day survival rate (chi2=40.805, P=0.000; chi2=4.425, P=0.035). CONCLUSIONS: Invasive-noninvasive sequential MV may not improve the outcome of senile patients with severe CAP, and ETI>=2 times and concurrent cerebrovascular disorders drastically lowered the survival rate. PMID- 26138424 TI - [A multicenter clinical study of bundle treatment for moderate or severe acute respiratory distress syndrome]. AB - OBJECTIVE: To investigate the efficacy of bundle treatment on patients with moderate or severe acute respiratory distress syndrome (ARDS). METHODS: A multicenter prospective observational study comparing the result of historical treatment strategy and bundle treatment was conducted. According to the new Berlin standard of definition, 73 patients with moderate or severe ARDS due to pulmonary factors, age from 18 to 65 years, admitted to Department of Critical Care Medicine of Taian Central Hospital and Handan Central Hospital were enrolled. Thirty-three patients admitted during September 2012 to May 2014 (prospective observation period) were enrolled as the bundle treatment group. Forty patients with matched disease history admitted from January 2010 to August 2012 were enrolled as the control group. The patients in bundle treatment group received bundle treatment based on the treatment strategy of primary diseases. Bundle treatment included restrictive fluid management, respiratory support, high dose ambroxol combined with Xuebijing injection, prevention of ventilation associated pneumonia (VAP), individualized sedation plan, installation of continuous blood purification treatment for critical patients. A special team was organized to ensure the successful implementation of all bundle measures. The acute physiology and chronic health evaluation II (APACHEII) score, oxygenation index, duration of mechanical ventilation, the length of intensive care unit (ICU) stay, incidence of VAP, and 28-day mortality 5 days after treatment were compared between two groups. RESULTS: There were no significant differences in basic characteristics of patients between the two groups, including gender, age, etiology, severity, etc. (all P>0.05) with comparability. Compared with the control group, there was no significant difference in APACHE II score 5 days after treatment in bundle treatment group (15.1+/-2.8 vs. 16.2+/-3.0, t=1.618, P=0.110). Compared with control group, oxygenation index in bundle treatment group was significantly improved [mmHg (1 mmHg=0.133 kPa): 135.4+/-34.5 vs. 117.1+/-34.2, t=-2.273, P=0.026), the duration of mechanical ventilation was obviously reduced (days: 8.70+/-2.50 vs. 10.10+/-2.67, t=2.308, P=0.024), incidence of VAP was significantly lower [18.2% (6/33) vs. 32.5% (13/40), chi2=5.027, P=0.025], and 28-day mortality rate was obviously lowered [24.2% (8/33) vs. 37.5% (15/40), chi2=4.372, P=0.037], the length of ICU stay shown no statistical difference (days: 10.40+/-1.94 vs. 11.30+/-2.34, t=1.620, P=0.110). CONCLUSIONS: Implementation of bundle treatment can significantly shorten the duration of mechanical ventilation, reduce the incidence of VAP, and improve the prognosis of patients. PMID- 26138425 TI - [Effect of sustained inflation with different degrees of negative pressure for sputum aspiration in patients with acute respiratory distress syndrome on lung recruitment]. AB - OBJECTIVE: To investigate the effect of different degrees of pressure of sustained inflation (SI) in patients with acute respiratory distress syndrome (ARDS) after lung recruitment as the result of different negative pressure for sputum aspiration. METHODS: A prospective single-blind randomized controlled trial was conducted. The factorial analysis of variance was adopted. 150 patients with ARDS admitted to the emergency intensive care unit (ICU) of Chongqing Three Gorges Central Hospital from January 2012 to December 2014 were enrolled, and they were randomly divided into S1, S2, S3 group, with 50 patients in each group, suction pressure varying from 150, 175, to 200 mmHg (1 mmHg=0.133 kPa) was respectively used in each group. Then the patients of each group were randomly subdivided into five subgroups of P0, P1, P2, P3, P4, with 10 patients in each group, and 0, 30, 35, 40, and 45 cmH2O (1 cmH2O=0.098 kPa) were used for control pulmonary inflation pressure, respectively. The respiratory mechanics and the hemodynamic parameters were recorded, and they were compared before and after the sputum aspiration as well as lung recruitment with sustained inflation. RESULTS: The lung recruitment volume (mL: 87.56+/-28.47 vs. 109.38+/-34.63, t=3.573, P=0.001) and lung static compliance [Cst (mL/cmH2O): 27.69+/-13.25 vs. 35.87+/ 17.47, t=2.814, P=0.004] after sputum aspiration in the 150 patients were significantly lower than those before the sputum aspiration, and peak airway pressure [PIP (cmH2O): 24.16+/-8.28 vs. 18.63+/-6.67, t=2.957, P=0.005], airway plateau pressure [Pplat (cmH2O): 21.28+/-9.14 vs. 17.47+/-7.26, t=2.089, P=0.032], and mean airway pressure [Pm (cmH2O): 13.26+/-4.65 vs. 10.41+/-3.54, t=3.271, P=0.001] were significantly higher than those before the treatment. There were no significant differences in the lung recruitment volume, Cst, PIP, Pplat and Pm between groups with different negative pressure for sputum aspiration (F value was 0.809, 0.986, 1.121, 0.910, 1.043, and P value was 0.452, 0.381, 0.335, 0.410, 0.361), but statistical significance was found among different groups of different lung recruitment pressures (F value was 3.581, 5.028, 3.064, 3.036, 4.050, and P value was 0.013, 0.002, 0.026, 0.027, 0.007). There was no interaction between the two factors. After pairwise comparison, under the same negative pressure for sputum aspiration, lung recruitment volume and Cst in different lung recruitment pressures subgroups (P1, P2, P3, P4) were significantly higher than those of P0 subgroup, and PIP, Pplat, and Pm were significantly lower than those of P0 subgroup. There was no significant difference among P1, P2, P3 and P4 groups. There were no significant differences in mean arterial pressure (MAP) and pulmonary arterial pressure (PAP) among different groups with negative pressures for sputum aspiration and different lung recruitment pressures (negative pressure for sputum aspiration: F=0.586, P=0.561, F=1.373, P=0.264; lung recruitment pressure: F=1.313, P=0.280, F=1.621, P=0.186), there was no interaction between the two factors (F=0.936, P=0.497, F=1.391, P=0.227). The difference of heart rate (HR) in different negative pressure for sputum aspiration groups was not significant (F=1.144, P=0.328), and there were significant differences in different lung recruitment pressure groups (F=3.297, P=0.019), there was no interaction between the two factors (F=1.277, P=0.280). After pairwise comparison, under the same negative pressure for sputum aspiration, HR in P3 and P4 subgroups was significantly higher than that in P0, P1, and P2 subgroups (all P<0.05). CONCLUSIONS: 30 cmH2O and 35 cmH2O were the suitable pressure for SI in ARDS patients, and they were not affected by different negative pressure for sputum aspiration. PMID- 26138426 TI - [A study of outer membrane protein and molecular epidemiology of carbapenem resistant Acinetobacter baumannii]. AB - OBJECTIVE: To study the characteristics of the distribution and drug resistance of Acinetobacter baumannii, and the epidemiology of the main strains among wards and hospitals, and to investigate the role of outer membrane protein in producing resistance against carbapenems. METHODS: 145 Acinetobacter baumannii strains were collected from July 2013 to July 2014 from Huangdao Hospital Affiliated to Qingdao University and 401st Army Hospital. Antimicrobial susceptibility test was carried out with K-B disk diffusion method. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) was used for DNA typing and test of homology. The carO gene of outer membrane protein was amplified by PCR, and the outer membrane proteins were extracted by ultrasonication and ultracentrifuge method from 30 randomly selected carbapenem-resistant Acinetobacter baumannii and 17 carbapenem-sensitive strains. Sodium dodecyl sulfate-polyacrylamide gel electropheresis (SDS-PAGE) was used to analyze the expressions of outer membrane proteins. RESULTS: 145 Acinetobacter baumannii strains were generally resistant to 16 common antimicrobial agents, with the highest susceptibility rate of 79.3% for minocycline, followed by susceptibility rate of 40.7% for amikacin. There were 128 carbapenem-resistant strains (resistance rate of 88.3%), 137 multidrug resistant strains and 126 extensively drug-resistant strains. The detection rates of carO gene were 97.7% (125/128) and 17.6% (3/17) in carbapenem-resistant and sensitive strains respectively. Around position of relative molecular mass 47,000, 16 of 17 sensitive isolates were expressed this protein, while 20 of 30 resistant ones were detected nothing or fade; 13 of 17 sensitive isolates were expressed around position of relative molecular mass 37,000 and 29,000 while 25 were detected nothing or fade around position of relative molecular mass 37,000 and 23 were detected nothing or fade around position of relative molecular mass 29,000 in 30 resistant ones. 145 Acinetobacter baumannii were classified into 8 types based on ERIC-PCR electrophoresis patterns, and the major prevalence types were type A (71 strains) and type E (37 strains). CONCLUSIONS: Drug resistance of clinically isolated Acinetobacter baumannii is a serious problem in two hospitals; drug-resistant strains are spread and epidemic among wards and hospitals. The carO gene of outer membrane protein is widespread in carbapenem resistant Acinetobacter baumannii. The loss or fading of outer membrane protein may play an important role in Acinetobacter baumannii resistance to carbapenems drugs. PMID- 26138427 TI - [Effect of curcumin on lipopolysaccharide induced matrix metalloprotease in human bronchial epithelial cell]. PMID- 26138428 TI - [The design and application of new anti splash breathing loop tube]. PMID- 26138429 TI - [Clinical application of laryngeal mask in pre-hospital and in-hospital first aid]. PMID- 26138430 TI - [The first human case of infection of highly pathogenic H7N9 avian influenza virus in Guizhou Province]. PMID- 26138431 TI - The Ski Protein is Involved in the Transformation Pathway of Aurora Kinase A. AB - Oncogenic kinase Aurora A (AURKA) has been found to be overexpresed in several tumors including colorectal, breast, and hematological cancers. Overexpression of AURKA induces centrosome amplification and aneuploidy and it is related with cancer progression and poor prognosis. Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life. Reduced levels of Ski resulted in centrosomes amplification and multipolar spindles formation, same as AURKA overexpressing cells. Importantly, overexpression of Ski wild type, but not S326D and S383D mutants inhibited centrosome amplification and cellular transformation induced by AURKA. Altogether, these results suggest that the Ski protein is a target in the transformation pathway mediated by the AURKA oncogene. PMID- 26138433 TI - Rate-Enhancing Roles of Water Molecules in Methyltrioxorhenium-Catalyzed Olefin Epoxidation by Hydrogen Peroxide. AB - Olefin epoxidation catalyzed by methyltrioxorhenium (MTO, CH3ReO3) is strongly accelerated in the presence of H2O. The participation of H2O in each of the elementary steps of the catalytic cycle, involving the formation of the peroxo complexes (CH3ReO2(eta(2)-O2), A, and CH3ReO(eta(2)-O2)2(H2O), B), as well as in their subsequent epoxidation of cyclohexene, was examined in aqueous acetonitrile. Experimental measurements demonstrate that the epoxidation steps exhibit only weak [H2O] dependence, attributed by DFT calculations to hydrogen bonding between uncoordinated H2O and a peroxo ligand. The primary cause of the observed H2O acceleration is the strong co-catalytic effect of water on the rates at which A and B are regenerated and consequently on the relative abundances of the three interconverting Re-containing species at steady state. Proton transfer from weakly coordinated H2O2 to the oxo ligands of MTO and A, resulting in peroxo complex formation, is directly mediated by solvent H2O molecules. Computed activation parameters and kinetic isotope effects, in combination with proton inventory experiments, suggest a proton shuttle involving one or (most favorably) two H2O molecules in the key ligand-exchange steps to form A and B from MTO and A, respectively. PMID- 26138432 TI - Innate immune system favors emergency monopoiesis at the expense of DC differentiation to control systemic bacterial infection in mice. AB - DCs are professional APCs playing a crucial role in the initiation of T-cell responses to combat infection. However, systemic bacterial infection with various pathogens leads to DC-depletion in humans and mice. The mechanisms of pathogen induced DC-depletion remain poorly understood. Previously, we showed that mice infected with Yersinia enterocolitica (Ye) had impaired de novo DC-development, one reason for DC-depletion. Here, we extend these studies to gain insight into the molecular mechanisms of DC-depletion and the impact of different bacteria on DC-development. We show that the number of bone marrow (BM) hematopoietic progenitors committed to the DC lineage is reduced following systemic infection with different Gram-positive and Gram-negative bacteria. This is associated with a TLR4- and IFN-gamma-signaling dependent increase of committed monocyte progenitors in the BM and mature monocytes in the spleen upon Ye-infection. Adoptive transfer experiments revealed that infection-induced monopoiesis occurs at the expense of DC-development. Our data provide evidence for a general response of hematopoietic progenitors upon systemic bacterial infections to enhance monocyte production, thereby increasing the availability of innate immune cells for pathogen control, whereas impaired DC-development leads to DC depletion, possibly driving transient immunosuppression in bacterial sepsis. PMID- 26138434 TI - Agar Diffusion Procedures for Susceptibility Testing of Malassezia pachydermatis: Evaluation of Mueller-Hinton Agar Plus 2 % Glucose and 0.5 ug/ml Methylene Blue as the Test Medium. AB - Aim of this study was to verify whether Mueller-Hinton agar supplemented with 2 % glucose and methylene blue (MH-GM), which is used for disk diffusion susceptibility testing of Candida species by the Clinical and Laboratory Standards Institute, is suitable for testing Malassezia pachydermatis. A variant of the disk diffusion procedure utilizing a 9-mm tablet was used to test 31 isolates against clotrimazole and miconazole using MH-GM as test medium. The MH GM agar optimally supported the growth of all M. pachydermatis isolates, provided that the yeast inoculum was prepared with a lipid source (Tween 40 and 80). Zone edges were frequently definite and clear, facilitating the measurement of zone size and minimizing subjectivity. The inhibition zones correlated with MIC values obtained in a broth dilution assay. The agar diffusion method with MH-GM as the test medium appears as a suitable procedure for testing the susceptibility of M. pachydermatis to CTZ and MCZ in clinical laboratories. This test format may allow processing a large number of isolates in epidemiological studies. This may in turn facilitate clarifying to what extent the problem "drug resistance" accounts for cases of treatment failure in dogs with Malassezia otitis and dermatitis. PMID- 26138436 TI - Angiographic Variation of the Internal Carotid Artery and its Branches in Horses. AB - OBJECTIVES: To record the angiographic anatomy of the equine internal carotid artery (ICA) using angiography techniques. STUDY DESIGN: In vitro descriptive study. SAMPLE POPULATION: Equine cadaver specimens (n = 50). METHODS: Head and neck specimens from horses of mixed breed, age, sex, and use without a history of guttural pouch disease had carotid and cerebral angiography using conventional (n = 7) and rotational angiography (43). Angiographic findings were verified by arterial latex casts. RESULTS: Variation in ICA anatomy was categorized into 4 groups: (1) the internal carotid and occipital arteries arising as a common trunk; (2) an aberrant branch of the extra-cranial ICA connected to the basilar artery; (3) an aberrant branch of the ICA ramifying into the surrounding tissue and not connected to any other vessels; and (4) an aberrant branch of the ICA giving rise to several smaller satellite branches, including connections to the caudal branch of the ipsilateral occipital artery. CONCLUSION: Rotational angiography is useful for identification of anatomic variation in the ICA that could be important in achieving vascular occlusion in the treatment of guttural pouch mycosis. PMID- 26138435 TI - Species Distribution, Virulence Factors, and Antifungal Susceptibility Among Candida parapsilosis Complex Isolates Recovered from Clinical Specimens. AB - The Candida parapsilosis complex has emerged as an important fungal pathogen. In spite of this, relatively little is known about its characteristics. Thus, the purposes of this study were (1) to determine by BanI-RFLP-assay the occurrence of C. parapsilosis complex species among 81 clinical isolates primarily identified as C. parapsilosis; (2) to evaluate their in vitro production of virulence factors; and (3) to compare their susceptibility profiles, grown as planktonic cells and biofilms, against amphotericin B, fluconazole, voriconazole, and caspofungin by following the Clinical and Laboratory Standards Institute (CLSI) guidelines. Seventy-seven isolates (95%) were identified as C. parapsilosis sensu stricto, 2 (2.5%) as C. orthopsilosis, and 2 (2.5%) as C. metapsilosis. Protease activity was detected in 29 (37.7%) isolates of C. parapsilosis sensu stricto, whereas only 7 (9.1%) exhibited phospholipase activity. None of the C. metapsilosis or C. orthopsilosis was able to produce protease or phospholipase. Biofilm production was detected in 35 (43.2%) isolates, among which 33 were C. parapsilosis sensu stricto and 2 were C. orthopsilosis. Antifungal resistance was uncommon; only one C. metapsilosis was fluconazole resistant. However, biofilm producing isolates showed a marked resistance to all antifungal agents tested, particularly to voriconazole. This knowledge could be of clinical relevance for guiding therapeutic decisions. PMID- 26138437 TI - An efficient synthesis of isoquinolines via rhodium-catalyzed direct C-H functionalization of arylhydrazines. AB - A highly efficient rhodium-catalyzed C-H activation of arylhydrazines and coupling with internal alkynes has been realized under mild conditions. The isoquinolines have been prepared in moderate to excellent yields in high efficiency. This methodology features the use of readily available starting materials, and a simple hydrazine moiety as a directing group, in the absence of an external metal co-oxidant under an air atmosphere. The C-H bond activation and the N-N bond cleavage have been successively realized under mild conditions. PMID- 26138438 TI - The option of sonographic guidance in Botulinum toxin injection for drooling in Parkinson's disease. AB - Parkinson's disease is a syndrome that frequently includes drooling, i.e., the involuntary spillage of saliva over the lip margin. Such drooling places a severe burden on both the health and the quality of life of Parkinsonian patients. Its origin lies in the impairment of oral motor control and swallowing associated with Parkinson's disease. It can be treated surgically or conservatively by reducing the production of saliva in the salivary glands, to which the parotid and submandibular glands make the greatest contribution. Botulinum neurotoxins A and B, administered to these glands, are in increasing use as treatment for drooling from various causes including Parkinson's disease. Wide knowledge was gathered about preferred drugs, dosages, injection sites and injection-guiding techniques, albeit without providing evidence-based guidance or a clear rationale for the mode of action of the medication or any information about further influential or predictive factors for safety and efficacy. However, it is essential that the relevant glands be targeted accurately; although this can be done by using anatomical landmarks, the use of sonographic guidance seems preferable. In the hands of a trained injector, sonography is a quick and non invasive imaging technique. PMID- 26138439 TI - Advanced stages of PD: interventional therapies and related patient-centered care. AB - During the last decades, symptomatic treatment of motor symptoms of Parkinson's disease (PD) improved continuously and is reflected by long-range independency of the patient during the disease course. However, advanced stages of PD still represent an important challenge to patients, caregivers and treating physicians. In patients with advanced PD, interventional therapy strategies are increasingly applied. These device-related treatment strategies using pump-based continuous dopaminergic stimulation (CDS) or deep brain stimulation (DBS) opened new treatment options especially if motor complications predominate. Well-designed clinical studies on these interventional therapeutic approaches provided class 1 evidence for the efficacy of DBS and CDS in advanced PD and opened new perspectives for their use in earlier disease stages also. Therefore, careful selection of patients amenable to the (semi)invasive therapy options becomes more and more important and requires an interdisciplinary setting that accounts for (i) optimal patient information and awareness, (ii) selection of best individual treatment modality, (iii) training of relatives and caregivers, (iv) management of complications, and (v) follow-up care. Here, we address these topics by summarizing current state-of-the-art in patient selection, providing specificities of treatment options and troubleshooting, and defining steps towards an optimized patient-centered care. Interventional therapies pioneer in the area of individualized treatment approaches for PD, and may be complemented in the future by biomarker-based improved stratification and by closed-loop systems for adaptive therapeutic strategies. In the present review, we summarize the proceedings of an Expert Workshop on Parkinson's disease held on November 22, 2014 in Frankfurt, Germany. PMID- 26138440 TI - Benchmark calculations of the adsorption of aromatic molecules on graphene. AB - Selecting the saturated graphene fragment as a model of graphene, we have investigated seven popular density functionals, including omegaB97X-D, B97-D, B LYP-D3, M05-2X, M06-2X, M11-L, and N12, for their performance in describing the adsorption of aromatic molecules on graphene. The best performing functionals are B97-D, B-LYP-D3, and omegaB97X-D. M05-2X, M06-2X, and M11-L significantly underestimate the adsorption strengths, while N12 fails completely in this respect. The effects of the basis sets and size of the saturated graphene fragments on the geometries, energies, and properties for the adsorption of aromatic molecules on graphene have also been studied. It was found that the small basis sets such as 6-31G(d) and jun-cc-pVDZ are not suitable for the accurate description of the adsorption of aromatic molecules on graphene. The size of selected graphene fragments has a little effect on both the omegaB97X-D and SCS-SAPT0 interaction energies, but the effects of the size of selected graphene fragments on the energy components are significant in some cases of the adsorption of aromatic molecules on graphene. The surprising weakness of electrostatic interactions by F substitution for the adsorption of F-substituted benzenes on graphene was explained using the energy component analysis. PMID- 26138441 TI - Definition of Failed Induction of Labor and Its Predictive Factors: Two Unsolved Issues of an Everyday Clinical Situation. AB - OBJECTIVE: The objectives of this review were to identify the predictive factors of induction of labor (IOL) failure or success as well as to highlight the current heterogeneity regarding the definition and diagnosis of failed IOL. MATERIALS AND METHODS: Only studies in which the main or secondary outcome was failed IOL, defined as not entering the active phase of labor after 24 h of prostaglandin administration +/- 12 h of oxytocin infusion, were included in the review. The data collected were: study design, definition of failed IOL, induction method, IOL indications, failed IOL rate, cesarean section because of failed IOL and predictors of failed IOL. RESULTS: The database search detected 507 publications. The main reason for exclusion was that the primary or secondary outcomes were not the predetermined definition of failed IOL (not achieving active phase of labor). Finally, 7 studies were eligible. The main predictive factors identified in the review were cervical status, evaluated by the Bishop score or cervical length. DISCUSSION: Failed IOL should be defined as the inability to achieve the active phase of labor, considering that the definition of IOL is to enter the active phase of labor. A universal definition of failed IOL is an essential requisite to analyze and obtain solid results and conclusions on this issue. An important finding of this review is that only 7 of all the studies reviewed assessed achieving the active phase of labor as a primary or secondary IOL outcome. Another conclusion is that cervical status remains the most important predictor of IOL outcome, although the value of the parameters explored up to now is limited. To find or develop predictive tools to identify those women exposed to IOL who may not reach the active phase of labor is crucial to minimize the risks and costs associated with IOL failure while opening a great opportunity for investigation. Therefore, other predictive tools should be studied in order to improve IOL outcome in terms of health and economic burden. PMID- 26138442 TI - MAP3K11 is a tumor suppressor targeted by the oncomiR miR-125b in early B cells. AB - MicroRNAs (miRNAs) are a class of small, non-coding RNAs that posttranscriptionally regulate gene expression and thereby control most, if not all, biological processes. Aberrant miRNA expression has been linked to a variety of human diseases including cancer, but the underlying molecular mechanism often remains unclear. Here we have screened a miRNA expression library in a growth factor-dependent mouse pre-B-cell system to identify miRNAs with oncogenic activity. We show that miR-125b is sufficient to render pre-B cells growth factor independent and demonstrate that continuous expression of miR-125b is necessary to keep these cells in a transformed state. Mechanistically, we find that the expression of miR-125b protects against apoptosis induced by growth factor withdrawal, and that it blocks the differentiation of pre-B to immature B cells. In consequence, miR-125b-transformed cells maintain expression of their pre-B cell receptor that provides signals for continuous proliferation and survival even in the absence of growth factor. Employing microarray analysis, we identified numerous targets of miR-125b, but only reconstitution of MAP3K11, a critical regulator of mitogen- and stress-activated kinase signaling, interferes with the cellular fitness of the transformed cells. Together, this indicates that MAP3K11 might function as an important tumor suppressor neutralized by oncomiR 125b in B-cell leukemia. PMID- 26138443 TI - Nuclear ULK1 promotes cell death in response to oxidative stress through PARP1. AB - Reactive oxygen species (ROS) may cause cellular damage and oxidative stress induced cell death. Autophagy, an evolutionarily conserved intracellular catabolic process, is executed by autophagy (ATG) proteins, including the autophagy initiation kinase Unc-51-like kinase (ULK1)/ATG1. Although autophagy has been implicated to have both cytoprotective and cytotoxic roles in the response to ROS, the role of individual ATG proteins, including ULK1, remains poorly characterized. In this study, we demonstrate that ULK1 sensitizes cells to necrotic cell death induced by hydrogen peroxide (H2O2). Moreover, we demonstrate that ULK1 localizes to the nucleus and regulates the activity of the DNA damage repair protein poly (ADP-ribose) polymerase 1 (PARP1) in a kinase-dependent manner. By enhancing PARP1 activity, ULK1 contributes to ATP depletion and death of H2O2-treated cells. Our study provides the first evidence of an autophagy independent prodeath role for nuclear ULK1 in response to ROS-induced damage. On the basis of our data, we propose that the subcellular distribution of ULK1 has an important role in deciding whether a cell lives or dies on exposure to adverse environmental or intracellular conditions. PMID- 26138444 TI - Fibril growth and seeding capacity play key roles in alpha-synuclein-mediated apoptotic cell death. AB - The role of extracellular alpha-synuclein (alpha-syn) in the initiation and the spreading of neurodegeneration in Parkinson's disease (PD) has been studied extensively over the past 10 years. However, the nature of the alpha-syn toxic species and the molecular mechanisms by which they may contribute to neuronal cell loss remain controversial. In this study, we show that fully characterized recombinant monomeric, fibrillar or stabilized forms of oligomeric alpha-syn do not trigger significant cell death when added individually to neuroblastoma cell lines. However, a mixture of preformed fibrils (PFFs) with monomeric alpha-syn becomes toxic under conditions that promote their growth and amyloid formation. In hippocampal primary neurons and ex vivo hippocampal slice cultures, alpha-syn PFFs are capable of inducing a moderate toxicity over time that is greatly exacerbated upon promoting fibril growth by addition of monomeric alpha-syn. The causal relationship between alpha-syn aggregation and cellular toxicity was further investigated by assessing the effect of inhibiting fibrillization on alpha-syn-induced cell death. Remarkably, our data show that blocking fibril growth by treatment with known pharmacological inhibitor of alpha-syn fibrillization (Tolcapone) or replacing monomeric alpha-syn by monomeric beta synuclein in alpha-syn mixture composition prevent alpha-syn-induced toxicity in both neuroblastoma cell lines and hippocampal primary neurons. We demonstrate that exogenously added alpha-syn fibrils bind to the plasma membrane and serve as nucleation sites for the formation of alpha-syn fibrils and promote the accumulation and internalization of these aggregates that in turn activate both the extrinsic and intrinsic apoptotic cell death pathways in our cellular models. Our results support the hypothesis that ongoing aggregation and fibrillization of extracellular alpha-syn play central roles in alpha-syn extracellular toxicity, and suggest that inhibiting fibril growth and seeding capacity constitute a viable strategy for protecting against alpha-syn-induced toxicity and slowing the progression of neurodegeneration in PD and other synucleinopathies. PMID- 26138445 TI - Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact. AB - Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co-expression of these two proteins predicted poor patient survival. Infection of GBM cells with HCMV led to upregulation of CD133 and other GSCS markers (Notch1, Sox2, Oct4, Nestin). HCMV infection also promoted the growth of GBM cells as neurospheres, a behavior typically displayed by GCSCs, and this phenotype was prevented by either chemical inhibition of the Notch1 pathway or by treatment with the anti-viral drug ganciclovir. GBM cells that maintained expression of HCMV-IE failed to differentiate into neuronal or astrocytic phenotypes. Our findings imply that HCMV infection induces phenotypic plasticity of GBM cells to promote GCSC features and may thereby increase the aggressiveness of this tumor. PMID- 26138446 TI - Technical aspects and effectiveness of percutaneous fetal therapies for large sacrococcygeal teratomas: cohort study and literature review. AB - OBJECTIVES: The objectives of this study were to evaluate the efficacy of minimally invasive ablation of high-risk large sacrococcygeal teratomas (SCT) and to compare the efficacy of vascular and interstitial tumor ablation. METHODS: This was a retrospective multicenter study including a cohort of fetuses with high-risk large SCTs between 2004 and 2010. In addition, we performed a systematic literature review of all cases that underwent tumor ablation in order to compare the survival rates after 'vascular' and 'interstitial' ablation. Statistical analysis was conducted using Bayesian methods. RESULTS: In our cohort, a total of 13 fetuses had high-risk large SCT and five of them underwent tumor ablation. The estimated difference in hydrops resolution rate between the fetal intervention and the no fetal intervention groups was 44.6% (95% credibility interval, 1.5 to 81.0%; Pdiff> 0 = 97.9%). The estimated difference in survival rate between the fetal intervention and the no fetal intervention groups was 31.0% (13.9 to 48.1%; Pdiff> 0 = 99.9%). We analyzed our five cases together with 28 cases from the literature and estimated the difference in survival rate between the vascular and interstitial ablation groups as 19.8% ( 13.1 to 50.1%; Pdiff> 0 = 88.3%). The estimated difference in hydrops resolution rate between the vascular and the interstitial ablation groups was 36.7% (-5.7 to 72.7%; Pdiff> 0 = 95.5%). CONCLUSION: Minimally invasive surgery seems to improve perinatal outcome in cases of high-risk large fetal SCT. Our findings suggest that 'vascular' ablation may improve outcome and may be more effective than 'interstitial' tumor ablation, but this hypothesis needs further investigation in a larger multicenter prospective study. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26138447 TI - A small outbreak of food poisoning among attendees of a public health thesis examination conference. PMID- 26138448 TI - Regulation of p53 during senescence in normal human keratinocytes. AB - p53, the guardian of the genome, is a tumor suppressor protein and critical for the genomic integrity of the cells. Many studies have shown that intracellular level of p53 is enhanced during replicative senescence in normal fibroblasts, and the enhanced level of p53 is viewed as the cause of senescence. Here, we report that, unlike in normal fibroblasts, the level of intracellular p53 reduces during replicative senescence and oncogene-induced senescence (OIS) in normal human keratinocytes (NHKs). We found that the intracellular p53 level was also decreased in age-dependent manner in normal human epithelial tissues. Senescent NHKs exhibited an enhanced level of p16(INK4A) , induced G2 cell cycle arrest, and lowered the p53 expression and transactivation activity. We found that low level of p53 in senescent NHKs was due to reduced transcription of p53. The methylation status at the p53 promoter was not altered during senescence, but senescent NHKs exhibited notably lower level of acetylated histone 3 (H3) at the p53 promoter in comparison with rapidly proliferating cells. Moreover, p53 knockdown in rapidly proliferating NHKs resulted in the disruption of fidelity in repaired DNA. Taken together, our study demonstrates that p53 level is diminished during replicative senescence and OIS and that such diminution is associated with H3 deacetylation at the p53 promoter. The reduced intracellular p53 level in keratinocytes of the elderly could be a contributing factor for more frequent development of epithelial cancer in the elderly because of the loss of genomic integrity of cells. PMID- 26138450 TI - Graphene-Based Flexible and Transparent Tunable Capacitors. AB - We report a kind of electric field tunable transparent and flexible capacitor with the structure of graphene-Bi1.5MgNb1.5O7 (BMN)-graphene. The graphene films with low sheet resistance were grown by chemical vapor deposition. The BMN thin films were fabricated on graphene by using laser molecular beam epitaxy technology. Compared to BMN films grown on Au, the samples on graphene substrates show better quality in terms of crystallinity, surface morphology, leakage current, and loss tangent. By transferring another graphene layer, we fabricated flexible and transparent capacitors with the structure of graphene-BMN-graphene. The capacitors show a large dielectric constant of 113 with high dielectric tunability of ~40.7 % at a bias field of 1.0 MV/cm. Also, the capacitor can work stably in the high bending condition with curvature radii as low as 10 mm. This flexible film capacitor has a high optical transparency of ~90 % in the visible light region, demonstrating their potential application for a wide range of flexible electronic devices. PMID- 26138451 TI - Facile Synthesis of Mn-Doped ZnO Porous Nanosheets as Anode Materials for Lithium Ion Batteries with a Better Cycle Durability. AB - Porous Zn1 - x Mn x O (x = 0.1, 0.2, 0.44) nanosheets were prepared by a low cost, large-scale production and simple approach, and the applications of these nanosheets as an anode material for Li-ion batteries (LIBs) were explored. Electrochemical measurements showed that the porous Zn0.8Mn0.2O nanosheets still delivered a stable reversible capacity of 210 mA h g(-1) at a current rate of 120 mA g(-1) up to 300 cycles. These results suggest that the facile synthetic method of producing porous Zn0.8Mn0.2O nanostructure can realize a better cycle durability with stable reversible capacity. PMID- 26138449 TI - The Neurogenic Potential of Astrocytes Is Regulated by Inflammatory Signals. AB - Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these 'reactive' astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage restricted astrocytes to either tumor necrosis factor alpha (TNF-alpha) (via nuclear factor-kappaB (NFkappaB)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-beta1 and peroxisome proliferator-activated receptor gamma (PPARgamma)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes. PMID- 26138452 TI - Green Approach for the Effective Reduction of Graphene Oxide Using Salvadora persica L. Root (Miswak) Extract. AB - Recently, green reduction of graphene oxide (GRO) using various natural materials, including plant extracts, has drawn significant attention among the scientific community. These methods are sustainable, low cost, and are more environmentally friendly than other standard methods of reduction. Herein, we report a facile and eco-friendly method for the bioreduction of GRO using Salvadora persica L. (S. persica L.) roots (miswak) extract as a bioreductant. The as-prepared highly reduced graphene oxide (SP-HRG) was characterized using powder X-ray diffraction (XRD), ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray photoelectron (XPS) spectroscopy, and transmission electron microscopy (TEM). Various results have confirmed that the biomolecules present in the root extract of miswak not only act as a bioreductant but also functionalize the surface of SP HRG by acting as a capping ligand to stabilize it in water and other solvents. The dispersion quality of SP-HRG in deionized water was investigated in detail by preparing different samples of SP-HRG with increasing concentration of root extract. Furthermore, the dispersibility of SP-HRG was also compared with chemically reduced graphene oxide (CRG). The developed eco-friendly method for the reduction of GRO could provide a better substitute for a large-scale production of dispersant-free graphene and graphene-based materials for various applications in both technological and biological fields such as electronics, nanomedicine, and bionic materials. PMID- 26138453 TI - Nanocrystalline hydroxyapatite enriched in selenite and manganese ions: physicochemical and antibacterial properties. AB - In this work, we used the co-precipitation method to synthesize hydroxyapatite (Mn-SeO3-HA) containing both selenium IV (approximately 3.60 wt.%) and manganese II (approximately 0.29 wt.%). Pure hydroxyapatite (HA), hydroxyapatite-containing manganese (II) ions (Mn-HA), and hydroxyapatite-containing selenite ions alone (SeO3-HA), prepared with the same method, were used as reference materials. The structures and physicochemical properties of all the obtained samples were investigated. PXRD studies showed that the obtained materials were homogeneous and consisted of apatite phase. Introducing selenites into the hydroxyapatite crystals considerably affects the size and degree of ordering. Experiments with transmission electron microscopy (TEM) showed that Mn-SeO3-HA crystals are very small, needle-like, and tend to form agglomerates. Fourier transform infrared spectroscopy (FT-IR) and solid-state nuclear magnetic resonance (ssNMR) were used to analyze the structure of the obtained material. Preliminary microbiological tests showed that the material demonstrated antibacterial activity against Staphylococcus aureus, yet such properties were not confirmed regarding Escherichia coli. PACS codes: 61, 76, 81. PMID- 26138454 TI - Larger medial femoral to tibial condylar dimension may trigger posterior root tear of medial meniscus. AB - PURPOSE: The major meniscal functions are load bearing, load distribution, and shock absorption by increasing the tibiofemoral joint (TFJ) contact area and dissipating axial loads by conversion into hoop stresses. The increased hoop strain stretches the meniscus in outward direction towards radius, causing extrusion, which is associated with the root tear and resultant degenerative osteoarthritis. Since the larger contact area of medial TFJ may increase the hoop stresses, we hypothesized that the larger medial femoral to tibial condylar dimension would contribute to the development of medial meniscus posterior root tear (MMPRT). Thus, the purpose of the study was to assess the relationship between MMPRT and medial femoral to tibial condylar dimension. METHODS: A case control study was conducted to compare medial femoral to tibial condylar dimensions of patients with complete MMPRT (n = 59) with those of demography matched controls (n = 59) during the period from 2010 to 2013. In each patient, MRIs were reviewed and several parameters were measured including articulation width of medial femoral condyle (MFC) at 0 degrees , 30 degrees , 60 degrees , and 90 degrees , medial tibial condyle (MTC) width, degree of meniscal extrusion, and medial femoral to tibial condylar width ratio (MFC/MTC) at 0 degrees , 30 degrees , 60 degrees , and 90 degrees , respectively. Demographic and radiographic data were assessed. RESULTS: A larger medial femoral to tibial condylar dimension was associated with MMPRT at 0 degrees and 30 degrees knee angles. Patients with MFC/MTC greater than 0.9 at 0 degrees also showed about 2.5-fold increase in the chance of MMPRT. Those with meniscal extrusion greater than 3 mm also had about 17.1 times greater chance for the presence of MMPRT accordingly. CONCLUSIONS: A larger medial femoral to tibial condylar dimension may be considered as one of the regional contributors to the outbreak of MMPRT, and medial femoral to tibial condylar width ratio greater than 0.9 at 0 degrees knee angle may be considered as a significant risk factor for MMPRT. LEVEL OF EVIDENCE: III. PMID- 26138455 TI - Is quality of life following hip arthroscopy in patients with chondrolabral pathology associated with impairments in hip strength or range of motion? AB - INTRODUCTION: If physical impairments that are associated with poorer outcomes can be identified in people with chondrolabral hip pathology, then rehabilitation programmes that target such modifiable impairments could potentially be established to improve quality of life. The aim of this study was to examine the relationship between quality-of-life PROs and physical impairment measurements in people with chondrolabral pathology post-hip arthroscopic surgery. METHODS: This was a cross-sectional study where multiple stepwise linear regression analyses were conducted to determine which physical impairment measurements were most associated with poorer quality-of-life patient-reported outcomes (PROs). Eighty four patients (42 women; all aged 36 +/- 10 years) with hip chondrolabral pathology 12- to 24-month post-hip arthroscopy were included. The Hip disability and Osteoarthritis Outcome Score Quality-of-life (HOOS-Q) subscale and International Hip Outcome Tool (IHOT-33) PROs were collected. Measurements of active hip ROM and strength were assessed. RESULTS: Modifiable post-surgical physical impairments were associated with PRO in patients with chondrolabral pathology. Greater hip flexion ROM was independently associated with better scores in both HOOS-Q and IHOT-33 (adjusted r 2 values ranged from 0.249 to 0.341). Greater hip adduction strength was independently associated with better HOOS-Q and IHOT-33 (adjusted r 2 0.227-0.317). Receiver Operator Curve analyses determined that the limit value for hip flexion ROM was 100 degrees (sensitivity 92 %, specificity 75 %), and hip adduction strength was 0.86 Nm/kg (sensitivity 96 %, specificity 70 %). CONCLUSIONS: Hip flexion ROM and adduction strength were associated with better quality-of-life PRO scores in patients with chondrolabral pathology 12- to 24-month post-hip arthroscopy. These impairments could be targeted by clinicians designing rehabilitation programmes to this patient group. LEVEL OF EVIDENCE: Cross-sectional study, Level IV. PMID- 26138456 TI - Verification of the pure alanine in PMMA tube dosimeter applicability for dosimetry of radiotherapy photon beams: a feasibility study. AB - Alanine dosimeters in the form of pure alanine powder in PMMA plastic tubes were investigated for dosimetry in a clinical application. Electron paramagnetic resonance (EPR) spectroscopy was used to measure absorbed radiation doses by detection of signals from radicals generated in irradiated alanine. The measurements were performed for low-dose ranges typical for single-fraction doses often used in external photon beam radiotherapy. First, the dosimeters were irradiated in a solid water phantom to establish calibration curves in the dose range from 0.3 to 3 Gy for 6 and 18 MV X-ray beams from a clinical linear accelerator. Next, the dosimeters were placed at various locations in an anthropomorphic pelvic phantom to measure the dose delivery of a conventional four-field box technique treatment plan to the pelvis. Finally, the doses measured with alanine dosimeters were compared against the doses calculated with a commercial treatment planning system (TPS). The results showed that the alanine dosimeters have a highly sensitive dose response with good linearity and no energy dependence in the dose range and photon beams used in this work. Also, a fairly good agreement was found between the in-phantom dose measurements with alanine dosimeters and the TPS dose calculations. The mean value of the ratios of measured to calculated dose values was found to be near unity. The measured points in the in-field region passed dose-difference acceptance criterion of 3% and those in the penumbral region passed distance-to-agreement acceptance criterion of 3 mm. These findings suggest that the pure alanine powder in PMMA tube dosimeter is a suitable option for dosimetry of radiotherapy photon beams. PMID- 26138458 TI - Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy? AB - Cytomegalovirus is the most important pathogen causing opportunistic infections in kidney allograft recipients. The occurrence of CMV disease is associated with higher morbidity, higher incidence of other opportunistic infections, allograft loss and death. Therefore, an efficient strategy to prevent CMV disease after kidney transplantation is required. Two options are currently available: pre emptive therapy based on regular CMV PCR monitoring and generalized antiviral prophylaxis during a defined period. In this review, we describe those two approaches, highlight the distinct advantages and risks of each strategy and summarize the four randomized controlled trials performed in this field so far. Taken this evidence together, pre-emptive therapy and anti-CMV prophylaxis are both equally potent in preventing CMV-associated complications; however, the pre emptive approach may have distinct advantages in allowing for development of long term anti-CMV immunity. We propose a risk-adapted use of these approaches based on serostatus, immunosuppressive therapy and availability of resources at a particular transplant centre. PMID- 26138459 TI - Very high coronary artery calcium score with normal myocardial perfusion SPECT imaging is associated with a moderate incidence of severe coronary artery disease. AB - PURPOSE: Myocardial perfusion imaging (MPI) has limitations in the presence of balanced multivessel disease (MVD) and left main (LM) coronary artery disease, occasionally resulting in false-normal results despite the high cardiovascular risk associated with this condition. The purpose of this study was to assess the incidence of severe coronary artery disease (CAD) in the presence of a very high Agatston coronary artery calcium (CAC) score (>1,000) in stable symptomatic patients without known CAD but with normal MPI results. METHODS: A total of 2,659 prospectively acquired consecutive patients were referred for MPI and evaluation of CAC score by CT. Of this patient population, 8 % (222/2,659) had ischemia without myocardial infarction (MI) on MPIand 11 % (298/2,659) had abnormal MPI (MI and/or ischemia). On presentation 1 % of the patients (26/2,659) were symptomatic, had a CAC score >1,000 and normal MPI results. The definition of normal MPI was strict and included a normal hemodynamic response without ischemic ECG changes and normal imaging, particularly absence of transient ischemic dilation. All of these 26 patients with a CAC score >1,000 and normal MPI findings underwent cardiac catheterization. RESULTS: Of these 26 patients, 58 % (15/26) had severe disease (>=70 % stenosis) leading to revascularization. Of this group, 47 % (7/15) underwent percutaneous intervention, and 53 % (8/15) underwent coronary artery bypass grafting. All of these 15 patients had either MVD (14/15) or LM coronary artery disease (1/15), and represented 0.6 % (15/2,659) of all referred patients (95 % CI 0.3 - 0.9 %). The majority, 90 % (8/9), had severe CAD with typical chest pain. CONCLUSION: A very high CAC score (>1,000) with normal MPI in a small subset of symptomatically stable patients was associated with a moderate incidence of severe CAD (95 % CI 37 - 77 %). Larger studies and/or a meta-analysis of small studies are needed to more precisely estimate the incidence of CAD in this population. This study also supports the concept that a normal MPI result in patients with severe CAD may be due to balanced MVD. PMID- 26138460 TI - Bone status of adult female butyrylcholinesterase gene-deficient mice. AB - Butyrylcholinesterase (BChE) degrades acetylcholine in addition to acetylcholinesterase (AChE) which is involved in embryonic development of limbs. Since BChE is expressed by osteoblast-like cells we asked whether it is functional in adult bone remodeling. We addressed this issue by analyzing BChE gene-deficient mice (BChE-KO). Bones were extracted from 16-week old female BChE KO and corresponding wild type mice (WT). Femoral bones were used for biomechanical testing and MUCT evaluation of cancellous and cortical bone. Also vertebrae Th12 and L1 were investigated with MUCT while L3 was used for tartrate resistant acidic phosphatase (TRAP) histomorphometry and Th10 for gene expression analysis by means of real-time RT-PCR. BChE-KO did not reveal significant differences in biomechanical bone strength and bone mineral density determined by MUCT. Microarchitecture of cancellous and cortical bone showed an increase in MUCT parameters like trabecular thickness, trabecular separation, and relative cortical bone area of femoral BChE-KO bone compared to WT. In vertebrae no changes of microstructure and mRNA expression were detected. However, osteoclast histomorphometry with TRAP stained sections demonstrated a significant increase in relative osteoclast number. In conclusion, in adult murine bone the role of BChE is limited to bone specific changes in microarchitecture and to an increase in relative number of bone resorbing osteoclasts whereas the main collagen resorbing enzyme Cathepsin-K (CtsK) was stably expressed. Besides, AChE might be able to compensate the lack of BChE. Thus, further analyses using bone tissue specific AChE BChE cre-lox double knockout mice would be helpful. PMID- 26138461 TI - Metformin reduces hepatic resistance and portal pressure in cirrhotic rats. AB - Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin +/- Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (alpha-smooth muscle actin, platelet-derived growth factor receptor beta polypeptide, transforming growth factor-betaR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation. PMID- 26138457 TI - Movement of regulatory RNA between animal cells. AB - Recent studies suggest that RNA can move from one cell to another and regulate genes through specific base-pairing. Mechanisms that modify or select RNA for secretion from a cell are unclear. Secreted RNA can be stable enough to be detected in the extracellular environment and can enter the cytosol of distant cells to regulate genes. Mechanisms that import RNA into the cytosol of an animal cell can enable uptake of RNA from many sources including other organisms. This role of RNA is akin to that of steroid hormones, which cross cell membranes to regulate genes. The potential diagnostic use of RNA in human extracellular fluids has ignited interest in understanding mechanisms that enable the movement of RNA between animal cells. Genetic model systems will be essential to gain more confidence in proposed mechanisms of RNA transport and to connect an extracellular RNA with a specific biological function. Studies in the worm C. elegans and in other animals have begun to reveal parts of this novel mechanism of cell-to-cell communication. Here, I summarize the current state of this nascent field, highlight the many unknowns, and suggest future directions. PMID- 26138463 TI - Intestinal scavenger receptor class B type I as a novel regulator of chylomicron production in healthy and diet-induced obese states. AB - The small intestine contributes to diabetic dyslipidemia through the overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles. An important regulator of chylomicron generation is dietary lipid absorption, underlining the potential involvement of intestinal lipid transporters for developing dyslipidemia. Intestinal expression of scavenger receptor class B type I (SR-BI) has been found to be upregulated in animal models of insulin resistance. Here we characterized the potential importance of SR-BI in contributing to chylomicron production and postprandial hypertriglyceridemia in vivo. Postprandial triglyceride (TG)-rich lipoprotein (TRL) production was characterized in hamsters treated with the SR-BI inhibitor to block lipid transport-1 (BLT-1) under healthy conditions or conditions of diet-induced obesity and dyslipidemia. BLT-1 (1 mg/kg) or vehicle was administered acutely in chow-fed hamsters or gavaged twice daily over 10 days during high-fructose, high fat, high-cholesterol (FFC) feeding. Effects of acute SR-BI inhibition by BLT-1 were confirmed in healthy fat-loaded rats. Finally, plasma lipid levels were compared between SR-BI(-/-) mice and their wild-type counterparts fed either chow or a 12-wk high-fat diet. Acute BLT-1 treatment reduced postprandial plasma and TRL TG levels in healthy hamsters and rats. Chronic BLT-1 treatment of FFC-fed hamsters blunted diet-induced weight gain and fasting hypertriglyceridemia, and lowered postprandial TRL-TG, -cholesterol, and -apoB48 levels. Finally, SR-BI(-/ ) mice displayed lower plasma and TRL TG levels relative to wild type, and diet induced weight gain and postprandial hypertriglyceridemia were hindered in SR-BI( /-) mice. We conclude that intestinal SR-BI is a critical regulator of postprandial lipoprotein production, emphasizing its potential as a target for preventing diabetic dyslipidemia. PMID- 26138462 TI - GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy. AB - Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABAA receptors by neurosteroids such as allopregnanolone and 3alpha,21-dihydroxy-5alpha-pregnan-20 one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE. PMID- 26138464 TI - Esophageal development and epithelial homeostasis. AB - The esophagus is a relatively simple organ that evolved to transport food and liquids through the thoracic cavity. It is the only part of the gastrointestinal tract that lacks any metabolic, digestive, or absorptive function. The mucosa of the adult esophagus is covered by a multilayered squamous epithelium with a remarkable similarity to the epithelium of the skin despite the fact that these tissues originate from two different germ layers. Here we review the developmental pathways involved in the establishment of the esophagus and the way these pathways regulate gut-airway separation. We summarize current knowledge of the mechanisms that maintain homeostasis in esophageal epithelial renewal in the adult and the molecular mechanism of the development of Barrett's metaplasia, the precursor lesion to esophageal adenocarcinoma. Finally, we examine the ongoing debate on the hierarchy of esophageal epithelial precursor cells and on the presence or absence of a specific esophageal stem cell population. Together the recent insights into esophageal development and homeostasis suggest that the pathways that establish the esophagus during development also play a role in the maintenance of the adult epithelium. We are beginning to understand how reflux of gastric content and the resulting chronic inflammation can transform the squamous esophageal epithelium to columnar intestinal type metaplasia in Barrett's esophagus. PMID- 26138465 TI - Inflammation-induced abnormalities in the subcellular localization and trafficking of the neurokinin 1 receptor in the enteric nervous system. AB - Activated G protein-coupled receptors traffic to endosomes and are sorted to recycling or degradative pathways. Endosomes are also a site of receptor signaling of sustained and pathophysiologically important processes, including inflammation. However, the mechanisms of endosomal sorting of receptors and the impact of disease on trafficking have not been fully defined. We examined the effects of inflammation on the subcellular distribution and trafficking of the substance P (SP) neurokinin 1 receptor (NK1R) in enteric neurons. We studied NK1R trafficking in enteric neurons of the mouse colon using immunofluorescence and confocal microscopy. The impact of inflammation was studied in IL10(-/-) piroxicam and trinitrobenzenesulfonic acid colitis models. NK1R was localized to the plasma membrane of myenteric and submucosal neurons of the uninflamed colon. SP evoked NK1R endocytosis and recycling. Deletion of beta-arrestin2, which associates with the activated NK1R, accelerated recycling. Inhibition of endothelin-converting enzyme-1 (ECE-1), which degrades endosomal SP, prevented recycling. Inflammation was associated with NK1R endocytosis in myenteric but not submucosal neurons. Whereas the NK1R in uninflamed neurons recycled within 60 min, NK1R recycling in inflamed neurons was delayed for >120 min, suggesting defective recycling machinery. Inflammation was associated with beta-arrestin2 upregulation and ECE-1 downregulation, which may contribute to the defective NK1R recycling. We conclude that inflammation evokes redistribution of NK1R from the plasma membrane to endosomes of myenteric neurons through enhanced SP release and defective NK1R recycling. Defective recycling may be secondary to upregulation of beta-arrestin2 and downregulation of ECE-1. Internalized NK1R may generate sustained proinflammatory signals that disrupt normal neuronal functions. PMID- 26138466 TI - Therapeutic targeting of bile acids. AB - The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control. PMID- 26138467 TI - Bimodal effect of oxidative stress in internal anal sphincter smooth muscle. AB - Changes in oxidative stress may affect basal tone and relaxation of the internal anal sphincter (IAS) smooth muscle in aging. We examined this issue by investigating the effects of the oxidative stress inducer 6-anilino-5,8 quinolinedione (LY-83583) in basal as well as U-46619-stimulated tone, and nonadrenergic, noncholinergic (NANC) relaxation in rat IAS. LY-83583, which works via generation of reactive oxygen species in living cells, produced a bimodal effect in IAS tone: lower concentrations (0.1 nM to 10 MUM) produced a concentration-dependent increase, while higher concentrations (50-100 MUM) produced a decrease in IAS tone. An increase in IAS tone by lower concentrations was associated with an increase in RhoA/Rho kinase (ROCK) activity. This was evident by the increase in RhoA/ROCK in the particulate fractions, in ROCK activity, and in the levels of phosphorylated (p) (Thr696)-myosin phosphatase target subunit 1 and p(Thr18/Ser19)-20-kDa myosin light chain. Conversely, higher concentrations of LY-83583 produced inhibitory effects on RhoA/ROCK. Interestingly, both the excitatory and inhibitory effects of LY-83583 in the IAS were reversed by superoxide dismutase. The excitatory effects of LY-83583 were found to resemble those with neuronal nitric oxide synthase (nNOS) inhibition by l-NNA, since it produced a significant increase in the IAS tone and attenuated NANC relaxation. These effects of LY-83583 and l-NNA were reversible by l arginine. This suggests the role of nNOS inhibition and RhoA/ROCK activation in the increase in IAS tone by LY-83583. These data have important implications in the pathophysiology and therapeutic targeting of rectoanal disorders, especially associated with IAS dysfunction. PMID- 26138468 TI - Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs. AB - It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models for preterm infants. Pigs were given either total parenteral nutrition (TPN, n = 14) or slowly advancing volumes (16-64 ml.kg(-1).day(-1)) of preterm infant formula (IF, n = 15) or bovine colostrum (BC, n = 13), both given as adjunct to parenteral nutrition. On day 5, both enteral diets increased intestinal mass (27 +/- 1 vs. 22 +/- 1 g/kg) and glucagon-like peptide 2 release, relative to TPN (P < 0.05). The incidence of mild NEC lesions was higher in IF than BC and TPN pigs (60 vs. 0 and 15%, respectively, P < 0.05). Only the IF pigs showed reduced gastric emptying and gastric inhibitory polypeptide release, and increased tissue proinflammatory cytokine levels (IL-1beta and IL-8, P < 0.05) and expression of immune-related genes (AOAH, LBP, CXCL10, TLR2), relative to TPN. The IF pigs also showed reduced intestinal villus-to-crypt ratio, lactose digestion, and some plasma amino acids (Arg, Cit, Gln, Tyr, Val), and higher intestinal permeability, compared with BC pigs (all P < 0.05). Colonic microbiota analyses showed limited differences among groups. Early feeding with formula induces intestinal dysfunction whereas bovine colostrum supports gut maturation when mother's milk is absent during the first week after preterm birth. A diet-dependent feeding guideline may be required for newborn preterm infants. PMID- 26138469 TI - Impact of ursodeoxycholic acid on a CCK1R cholesterol-binding site may contribute to its positive effects in digestive function. AB - Dysfunction of the type 1 cholecystokinin (CCK) receptor (CCK1R) as a result of increased gallbladder muscularis membrane cholesterol has been implicated in the pathogenesis of cholesterol gallstones. Administration of ursodeoxycholic acid, which is structurally related to cholesterol, has been shown to have beneficial effects on gallstone formation. Our aims were to explore the possible direct effects and mechanism of action of bile acids on CCK receptor function. We studied the effects of structurally related hydrophobic chenodeoxycholic acid and hydrophilic ursodeoxycholic acid in vitro on CCK receptor function in the setting of normal and elevated membrane cholesterol. We also examined their effects on a cholesterol-insensitive CCK1R mutant (Y140A) disrupting a key site of cholesterol action. The results show that, similar to the impact of cholesterol on CCK receptors, bile acid effects were limited to CCK1R, with no effects on CCK2R. Chenodeoxycholic acid had a negative impact on CCK1R function, while ursodeoxycholic acid had no effect on CCK1R function in normal membranes but was protective against the negative impact of elevated cholesterol on this receptor. The cholesterol-insensitive CCK1R mutant Y140A was resistant to effects of both bile acids. These data suggest that bile acids compete with the action of cholesterol on CCK1R, probably by interacting at the same site, although the conformational impact of each bile acid appears to be different, with ursodeoxycholic acid capable of correcting the abnormal conformation of CCK1R in a high-cholesterol environment. This mechanism may contribute to the beneficial effect of ursodeoxycholic acid in reducing cholesterol gallstone formation. PMID- 26138471 TI - Emerging drugs for preeclampsia--the endothelium as a target. AB - Preeclampsia, the development of new onset hypertension and proteinuria during pregnancy, affects ~ 3 - 8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality. Despite the potentially devastating effects of this disease on the mother and the baby and the recent advances in understanding some of the pathological mechanisms responsible for the progression of preeclampsia, there are still few therapies available to manage the disease. The maternal syndrome of preeclampsia is characterized by systemic endothelial dysfunction; therefore, agents that improve endothelial function may hold promise to alleviate the symptoms of preeclampsia, delay the necessity for preterm delivery and improve neonatal outcomes. This brief review will focus on two therapies that are already approved for use in the US for other indications: PDE 5 inhibition to preserve nitric oxide - cGMP signaling to promote vasodilation and inhibition of the endothelin type A receptor to reduce vascular contraction. PMID- 26138473 TI - Effects of NH3 PECVD treatment time on the performance of multiwall carbon nanotubes for antibody immobilization. AB - This work presents an amino plasma-enhanced chemical vapour deposition (NH3 PECVD) treatment to modify multiwall carbon nanotubes (MWCNTs) for the immobilization of antibodies (IgG-gold), and the effects of treatment time were studied. A titanium nitride (TiN) buffer layer and a nickel catalyst layer were deposited on silicon substrates for synthesis of MWCNTs using thermal CVD. The MWCNTs were modified by amine (NH2 (-) ) or amino (NH(-) ) functional groups for 1, 3, and 5 min by PECVD, respectively. Mouse IgG-golds were immobilized on the modified MWCNTs using glutaraldehyde (GA) as a crosslinker. The performance of the modified MWCNTs was characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), Fourier transform infrared spectroscopy (FT IR), contact angle system (CA), X-ray photoelectron spectroscopy (XPS, ESCA), and UV-visible spectroscopy. Results show that the efficiency of IgG-gold immobilization was increased with the increase of NH3 PECVD treatment time. The NH3 PECVD treatment changed the surface properties of the MWCNTs, tuning them more hydrophilic without affecting their structure. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1343-1351, 2016. PMID- 26138472 TI - Blockade of interferon-gamma normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus. AB - OBJECTIVE: To assess the safety and immunologic impact of inhibiting interferon gamma (IFNgamma) with AMG 811, a human IgG1 monoclonal antibody against IFNgamma, in patients with systemic lupus erythematosus (SLE). METHODS: Twenty-six patients with mild-to-moderate, stable SLE were administered placebo or a single dose of AMG 811, ranging from 2 mg to 180 mg subcutaneously or 60 mg intravenously. RESULTS: Similar to results previously reported following inhibition of type I IFNs, treatment of SLE patients with AMG 811 led to a dose-dependent modulation of the expression of genes associated with IFN signaling, as assessed by microarray analysis of the whole blood. The list of impacted genes overlapped with that identified by stimulating human whole blood with IFNgamma and with those gene sets reported in the literature to be differentially expressed in SLE patients. Serum levels of IFNgamma-induced chemokines, including IFNgamma inducible protein 10 (IP-10), were found to be elevated at baseline in SLE patients as compared to healthy volunteers. In contrast to previously reported results from studies using type I IFN-blocking agents, treatment with AMG 811 led to dose-related reductions in the serum levels of CXCL10 (IP-10). CONCLUSION: The scope and nature of the biomarkers impacted by AMG 811 support targeting of IFNgamma as a therapeutic strategy for SLE. PMID- 26138474 TI - The Influence of Gonadal Steroid Hormones on Immunoreactive Kisspeptin in the Preoptic Area and Arcuate Nucleus of Developing Agonadal Mice with a Genetic Disruption of Steroidogenic Factor 1. AB - Kisspeptin, a regulator of reproductive function and puberty in mammals, is expressed in the rostral (anteroventral) periventricular nucleus (AVPV) and arcuate nucleus (Arc), and its expression is at least partially regulated by estradiol in rodents. The aim of the present study was to determine contributions of genetic factors and gonadal steroid hormones to the sexual differentiation of kisspeptin-immunoreactive (kisspeptin-ir) cell populations in the AVPV and Arc during postnatal development using agonadal steroidogenic factor 1 (SF-1) knockout (KO) mice. To examine the effects of gonadal hormones on pubertal development of kisspeptin neurons, SF-1 KO mice were treated with estradiol benzoate (EB) from postnatal day (P)25 to P36, and their brains were examined at P36. No sex differences were observed in the SF-1 KO mice during postnatal development and after treatment with EB - which failed to increase the number of kisspeptin-ir cells at P36 to the levels found in wild-type (WT) control females. This suggests that specific time periods of estradiol actions or other factors are needed for sexual differentiation of the pattern of immunoreactive kisspeptin in the AVPV. Kisspeptin immunoreactivity in the Arc was significantly higher in gonadally intact WT and SF-1 KO females than in male mice at P36 during puberty. Further, in WT and SF-1 KO females, but not in males, adult levels were reached at P36. This suggests that maturation of the kisspeptin system in the Arc differs between sexes and is regulated by gonad-independent mechanisms. PMID- 26138475 TI - A common Shox2-Nkx2-5 antagonistic mechanism primes the pacemaker cell fate in the pulmonary vein myocardium and sinoatrial node. AB - In humans, atrial fibrillation is often triggered by ectopic pacemaking activity in the myocardium sleeves of the pulmonary vein (PV) and systemic venous return. The genetic programs that abnormally reinforce pacemaker properties at these sites and how this relates to normal sinoatrial node (SAN) development remain uncharacterized. It was noted previously that Nkx2-5, which is expressed in the PV myocardium and reinforces a chamber-like myocardial identity in the PV, is lacking in the SAN. Here we present evidence that in mice Shox2 antagonizes the transcriptional output of Nkx2-5 in the PV myocardium and in a functional Nkx2 5(+) domain within the SAN to determine cell fate. Shox2 deletion in the Nkx2 5(+) domain of the SAN caused sick sinus syndrome, associated with the loss of the pacemaker program. Explanted Shox2(+) cells from the embryonic PV myocardium exhibited pacemaker characteristics including node-like electrophysiological properties and the capability to pace surrounding Shox2(-) cells. Shox2 deletion led to Hcn4 ablation in the developing PV myocardium. Nkx2-5 hypomorphism rescued the requirement for Shox2 for the expression of genes essential for SAN development in Shox2 mutants. Similarly, the pacemaker-like phenotype induced in the PV myocardium in Nkx2-5 hypomorphs reverted back to a working myocardial phenotype when Shox2 was simultaneously deleted. A similar mechanism is also adopted in differentiated embryoid bodies. We found that Shox2 interacts with Nkx2-5 directly, and discovered a substantial genome-wide co-occupancy of Shox2, Nkx2-5 and Tbx5, further supporting a pivotal role for Shox2 in the core myogenic program orchestrating venous pole and pacemaker development. PMID- 26138476 TI - Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling. AB - Transcription-regulating long non-coding RNAs (lncRNAs) have the potential to control the site-specific expression of thousands of target genes. Previously, we showed that Evf2, the first described ultraconserved lncRNA, increases the association of transcriptional activators (DLX homeodomain proteins) with key DNA enhancers but represses gene expression. In this report, mass spectrometry shows that the Evf2-DLX1 ribonucleoprotein (RNP) contains the SWI/SNF-related chromatin remodelers Brahma-related gene 1 (BRG1, SMARCA4) and Brahma-associated factor (BAF170, SMARCC2) in the developing mouse forebrain. Evf2 RNA colocalizes with BRG1 in nuclear clouds and increases BRG1 association with key DNA regulatory enhancers in the developing forebrain. While BRG1 directly interacts with DLX1 and Evf2 through distinct binding sites, Evf2 directly inhibits BRG1 ATPase and chromatin remodeling activities. In vitro studies show that both RNA-BRG1 binding and RNA inhibition of BRG1 ATPase/remodeling activity are promiscuous, suggesting that context is a crucial factor in RNA-dependent chromatin remodeling inhibition. Together, these experiments support a model in which RNAs convert an active enhancer to a repressed enhancer by directly inhibiting chromatin remodeling activity, and address the apparent paradox of RNA-mediated stabilization of transcriptional activators at enhancers with a repressive outcome. The importance of BRG1/RNA and BRG1/homeodomain interactions in neurodevelopmental disorders is underscored by the finding that mutations in Coffin-Siris syndrome, a human intellectual disability disorder, localize to the BRG1 RNA-binding and DLX1-binding domains. PMID- 26138477 TI - A trans-homologue interaction between reciprocally imprinted miR-127 and Rtl1 regulates placenta development. AB - The paternally expressed imprinted retrotransposon-like 1 (Rtl1) is a retrotransposon-derived gene that has evolved a function in eutherian placentation. Seven miRNAs, including miR-127, are processed from a maternally expressed antisense Rtl1 transcript (Rtl1as) and regulate Rtl1 levels through RNAi-mediated post-transcriptional degradation. To determine the relative functional role of Rtl1as miRNAs in Rtl1 dosage, we generated a mouse specifically deleted for miR-127. The miR-127 knockout mice exhibit placentomegaly with specific defects within the labyrinthine zone involved in maternal-fetal nutrient transfer. Although fetal weight is unaltered, specific Rtl1 transcripts and protein levels are increased in both the fetus and placenta. Phenotypic analysis of single (DeltamiR-127/Rtl1 or miR-127/DeltaRtl1) and double (DeltamiR-127/DeltaRtl1) heterozygous miR-127- and Rtl1-deficient mice indicate that Rtl1 is the main target gene of miR-127 in placental development. Our results demonstrate that miR-127 is an essential regulator of Rtl1, mediated by a trans-homologue interaction between reciprocally imprinted genes on the maternally and paternally inherited chromosomes. PMID- 26138478 TI - Pbx1-dependent control of VMC differentiation kinetics underlies gross renal vascular patterning. AB - The architecture of an organ's vascular bed subserves its physiological function and metabolic demands. However, the mechanisms underlying gross vascular patterning remain elusive. Using intravital dye labeling and 3D imaging, we discovered that systems-level vascular patterning in the kidney is dependent on the kinetics of vascular mural cell (VMC) differentiation. Conditional ablation of the TALE transcription factor Pbx1 in renal VMC progenitors in the mouse led to the premature upregulation of PDGFRbeta, a master initiator of VMC-blood vessel association. This precocious VMC differentiation resulted in nonproductive angiogenesis, abnormal renal arterial tree patterning and neonatal death consistent with kidney dysfunction. Notably, we establish that Pbx1 directly represses Pdgfrb, and demonstrate that decreased Pdgfrb dosage in conditional Pbx1 mutants substantially rescues vascular patterning defects and neonatal survival. These findings identify, for the first time, an in vivo transcriptional regulator of PDGFRbeta, and reveal a previously unappreciated role for VMCs in systems-level vascular patterning. PMID- 26138480 TI - Evaluation of the efficacy and safety of lanreotide in combination with targeted therapies in patients with neuroendocrine tumours in clinical practice: a retrospective cross-sectional analysis. AB - BACKGROUND: Based on the mechanism of action, combining somatostatin analogues (SSAs) with mTOR inhibitors or antiangiogenic agents may provide synergistic effects for the treatment of patients with neuroendocrine tumours (NETs). Herein, we investigate the use of these treatment combinations in clinical practice. METHODS: This retrospective cross-sectional analysis of patients with NETs treated with the SSA lanreotide and targeted therapies at 35 Spanish hospitals evaluated the efficacy and safety of lanreotide treatment combinations in clinical practice. The data of 159 treatment combinations with lanreotide in 133 patients was retrospectively collected. RESULTS: Of the 133 patients, with a median age of 59.4 (16-83) years, 70 (52.6%) patients were male, 64 (48.1%) had pancreatic NET, 23 (17.3%) had ECOG PS >= 2, 41 (30.8%) had functioning tumours, 63 (47.7%) underwent surgery of the primary tumour, 45 (33.8%) had received prior chemotherapy, and 115 (86.5%) had received prior SSAs. 115 patients received 1 lanreotide treatment combination and 18 patients received between 2 and 5 combinations. Lanreotide was mainly administered in combination with everolimus (73 combinations) or sunitinib (61 combinations). The probability of being progression-free was 78.5% (6 months), 68.6% (12 months) and 57.0% (18 months) for patients who only received everolimus plus lanreotide (n = 57) and 89.3% (6 months), 73.0% (12 months), and 67.4% (18 months) for patients who only received sunitinib and lanreotide (n = 50). In patients who only received everolimus plus lanreotide the median time-to-progression from the initiation of lanreotide combination treatment was 25.8 months (95% CI, 11.3, 40.3) and it had not yet been reached among the subgroup of patients only receiving sunitinib plus lanreotide. The safety profile of the combination treatment was comparable to that of the targeted agent alone. CONCLUSIONS: The combination of lanreotide and targeted therapies, mainly everolimus and sunitinib, is widely used in clinical practice without unexpected toxicities and suggests efficacy that should be explored in randomized prospective clinical trials. PMID- 26138479 TI - Ectopic Atoh1 expression drives Merkel cell production in embryonic, postnatal and adult mouse epidermis. AB - Merkel cells are mechanosensitive skin cells whose production requires the basic helix-loop-helix transcription factor Atoh1. We induced ectopic Atoh1 expression in the skin of transgenic mice to determine whether Atoh1 was sufficient to create additional Merkel cells. In embryos, ectopic Atoh1 expression drove ectopic expression of the Merkel cell marker keratin 8 (K8) throughout the epidermis. Epidermal Atoh1 induction in adolescent mice similarly drove widespread K8 expression in glabrous skin of the paws, but in the whisker pads and body skin ectopic K8+ cells were confined to hair follicles and absent from interfollicular regions. Ectopic K8+ cells acquired several characteristics of mature Merkel cells in a time frame similar to that seen during postnatal development of normal Merkel cells. Although ectopic K8+ cell numbers decreased over time, small numbers of these cells remained in deep regions of body skin hair follicles at 3 months post-induction. In adult mice, greater numbers of ectopic K8+ cells were created by Atoh1 induction during anagen versus telogen and following disruption of Notch signaling by conditional deletion of Rbpj in the epidermis. Our data demonstrate that Atoh1 expression is sufficient to produce new Merkel cells in the epidermis, that epidermal cell competency to respond to Atoh1 varies by skin location, developmental age and hair cycle stage, and that the Notch pathway plays a key role in limiting epidermal cell competency to respond to Atoh1 expression. PMID- 26138481 TI - The predictive validity of a modified Japanese Nursing Association fall risk assessment tool: A retrospective cohort study. AB - BACKGROUND: Patient falls are the most common nursing care-related adverse event in hospitals. Extensive literature has been published on the predictive validity of fall risk assessment tools; however, there have been no studies examining the changes in predictive validity at different observation periods among hospital inpatients. OBJECTIVES: To examine the predictive validity of a modified Japanese Nursing Association fall risk assessment tool and to compare its predictive validity at observation periods of 7, 14, 21, and 28 days. DESIGN: Retrospective cohort design. SETTINGS: Twelve wards of a 600-bed university hospital in Japan. PARTICIPANTS: Patients 15 years and older admitted over a six-month period were enrolled. Patients were excluded if they were admitted to the intensive care unit or neuropsychiatry ward, had no fall risk assessment results within two days of admission, or had inconsistent assessment results. METHODS: Falls were observed for 28 days following admission. Predictive validity was evaluated using the area under the receiver operating curve, sensitivity, specificity, and positive and negative likelihood ratios at 7-, 14-, 21-, and 28-day observation points. Faller prevalence in each observation sample was adjusted for consistency using a bootstrap sampling method. All predictive validity indices were then recalculated and compared. RESULTS: A total of 4144 patients were admitted and 67 patients fell (1.6% faller prevalence) within 28 days of admission. The modified Japanese Nursing Association fall risk assessment tool showed a sensitivity of 0.82, specificity of 0.71, positive likelihood ratio of 2.83, and negative likelihood ratio of 0.26 at a cut-point of >=6, and the area under the receiver operating curve was 0.83. Predictive validity in the 7-day observation sample was significantly higher than the 14- and 28-day samples, but no significant difference was found relative to the 21-day observation sample. CONCLUSIONS: The modified Japanese Nursing Association fall risk assessment tool demonstrated good predictive validity in a Japanese university hospital, but further evaluation is needed for other validity values and reliability. The findings from this study may indicate that predictive validity indices vary by the length of observation period and faller prevalence, but these findings need to be examined further. PMID- 26138482 TI - Mediator tail subunits can form amyloid-like aggregates in vivo and affect stress response in yeast. AB - The Med2, Med3 and Med15 proteins form a heterotrimeric subdomain in the budding yeast Mediator complex. This Med15 module is an important target for many gene specific transcription activators. A previous proteome wide screen in yeast identified Med3 as a protein with priogenic potential. In the present work, we have extended this observation and demonstrate that both Med3 and Med15 form amyloid-like protein aggregates under H2O2 stress conditions. Amyloid formation can also be stimulated by overexpression of Med3 or of a glutamine-rich domain present in Med15, which in turn leads to loss of the entire Med15 module from Mediator and a change in stress response. In combination with genome wide transcription analysis, our data demonstrate that amyloid formation can change the subunit composition of Mediator and thereby influence transcriptional output in budding yeast. PMID- 26138483 TI - A fungicide-responsive kinase as a tool for synthetic cell fate regulation. AB - Engineered biological systems that precisely execute defined tasks have major potential for medicine and biotechnology. For instance, gene- or cell-based therapies targeting pathogenic cells may replace time- and resource-intensive drug development. Engineering signal transduction systems is a promising, yet presently underexplored approach. Here, we exploit a fungicide-responsive heterologous histidine kinase for pathway engineering and synthetic cell fate regulation in the budding yeast Saccharomyces cerevisiae. Rewiring the osmoregulatory Hog1 MAPK signalling system generates yeast cells programmed to execute three different tasks. First, a synthetic negative feedback loop implemented by employing the fungicide-responsive kinase and a fungicide resistant derivative reshapes the Hog1 activation profile, demonstrating how signalling dynamics can be engineered. Second, combinatorial integration of different genetic parts including the histidine kinases, a pathway activator and chemically regulated promoters enables control of yeast growth and/or gene expression in a two-input Boolean logic manner. Finally, we implemented a genetic 'suicide attack' system, in which engineered cells eliminate target cells and themselves in a specific and controllable manner. Taken together, fungicide responsive kinases can be applied in different constellations to engineer signalling behaviour. Sensitizing engineered cells to existing chemicals may be generally useful for future medical and biotechnological applications. PMID- 26138484 TI - Phosphorylation regulates the Star-PAP-PIPKIalpha interaction and directs specificity toward mRNA targets. AB - Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIalpha interaction. We show that S6 is phosphorylated by CKIalpha within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIalpha. Unlike the CKIalpha mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIalpha activity. S6 phosphorylation together with coactivator PIPKIalpha controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3'-end processing. PMID- 26138485 TI - Bacteriophage GIL01 gp7 interacts with host LexA repressor to enhance DNA binding and inhibit RecA-mediated auto-cleavage. AB - The SOS response in Eubacteria is a global response to DNA damage and its activation is increasingly associated with the movement of mobile genetic elements. The temperate phage GIL01 is induced into lytic growth using the host's SOS response to genomic stress. LexA, the SOS transcription factor, represses bacteriophage transcription by binding to a set of SOS boxes in the lysogenic promoter P1. However, LexA is unable to efficiently repress GIL01 transcription unless the small phage-encoded protein gp7 is also present. We found that gp7 forms a stable complex with LexA that enhances LexA binding to phage and cellular SOS sites and interferes with RecA-mediated auto-cleavage of LexA, the key step in the initiation of the SOS response. Gp7 did not bind DNA, alone or when complexed with LexA. Our findings suggest that gp7 induces a LexA conformation that favors DNA binding but disfavors LexA auto-cleavage, thereby altering the dynamics of the cellular SOS response. This is the first account of an accessory factor interacting with LexA to regulate transcription. PMID- 26138486 TI - Identification of in vivo DNA-binding mechanisms of Pax6 and reconstruction of Pax6-dependent gene regulatory networks during forebrain and lens development. AB - The transcription factor Pax6 is comprised of the paired domain (PD) and homeodomain (HD). In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific subpopulations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification. Pax6 also regulates the entire lens developmental program. To reconstruct Pax6-dependent gene regulatory networks (GRNs), ChIP-seq studies were performed using forebrain and lens chromatin from mice. A total of 3514 (forebrain) and 3723 (lens) Pax6 containing peaks were identified, with ~70% of them found in both tissues and thereafter called 'common' peaks. Analysis of Pax6-bound peaks identified motifs that closely resemble Pax6-PD, Pax6-PD/HD and Pax6-HD established binding sequences. Mapping of H3K4me1, H3K4me3, H3K27ac, H3K27me3 and RNA polymerase II revealed distinct types of tissue-specific enhancers bound by Pax6. Pax6 directly regulates cortical neurogenesis through activation (e.g. Dmrta1 and Ngn2) and repression (e.g. Ascl1, Fezf2, and Gsx2) of transcription factors. In lens, Pax6 directly regulates cell cycle exit via components of FGF (Fgfr2, Prox1 and Ccnd1) and Wnt (Dkk3, Wnt7a, Lrp6, Bcl9l, and Ccnd1) signaling pathways. Collectively, these studies provide genome-wide analysis of Pax6-dependent GRNs in lens and forebrain and establish novel roles of Pax6 in organogenesis. PMID- 26138487 TI - Structural basis for substrate recognition and processive cleavage mechanisms of the trimeric exonuclease PhoExo I. AB - Nucleases play important roles in nucleic acid processes, such as replication, repair and recombination. Recently, we identified a novel single-strand specific 3'-5' exonuclease, PfuExo I, from the hyperthermophilic archaeon Pyrococcus furiosus, which may be involved in the Thermococcales-specific DNA repair system. PfuExo I forms a trimer and cleaves single-stranded DNA at every two nucleotides. Here, we report the structural basis for the cleavage mechanism of this novel exonuclease family. A structural analysis of PhoExo I, the homologous enzyme from P. horikoshii OT3, showed that PhoExo I utilizes an RNase H-like active site and possesses a 3'-OH recognition site ~9 A away from the active site, which enables cleavage at every two nucleotides. Analyses of the heterotrimeric and monomeric PhoExo I activities showed that trimerization is indispensable for its processive cleavage mechanism, but only one active site of the trimer is required. PMID- 26138489 TI - Anticholinergic Activity and Alzheimer's Disease. PMID- 26138488 TI - Tight regulation of plant immune responses by combining promoter and suicide exon elements. AB - Effector-triggered immunity (ETI) is activated when plant disease resistance (R) proteins recognize the presence of pathogen effector proteins delivered into host cells. The ETI response generally encompasses a defensive 'hypersensitive response' (HR) that involves programmed cell death at the site of pathogen recognition. While many R protein and effector protein pairs are known to trigger HR, other components of the ETI signaling pathway remain elusive. Effector genes regulated by inducible promoters cause background HR due to leaky protein expression, preventing the generation of relevant transgenic plant lines. By employing the HyP5SM suicide exon, we have developed a strategy to tightly regulate effector proteins such that HR is chemically inducible and non-leaky. This alternative splicing-based gene regulation system was shown to successfully control Bs2/AvrBs2-dependent and RPP1/ATR1Delta51-dependent HR in Nicotiana benthamiana and Nicotiana tabacum, respectively. It was also used to generate viable and healthy transgenic Arabidopsis thaliana plants that inducibly initiate HR. Beyond enabling studies on the ETI pathway, our regulatory strategy is generally applicable to reduce or eliminate undesired background expression of transgenes. PMID- 26138490 TI - Serum Anticholinergic Activity as an Index of Anticholinergic Activity Load in Alzheimer's Disease. AB - We reported a procedure of serum anticholinergic activity (SAA) measurement and the reliability and reproducibility of the receptor binding assay, and we also described the usefulness of SAA measurement reflecting the anticholinergic activity (AA) in the central nervous system (CNS). According to the results of a 10 times repeated measurement of standard atropine binding, the relative error was between -5.5 and +3.7%, and we considered that measurement of SAA in our studies is accurate and validated. Downregulation of acetylcholine activates inflammation in both CNS and peripheral tissue, which causes AA in both sites. Therefore, changes of AA in the CNS link with SAA in the peripheral system even if a substance having AA does not penetrate through the blood-brain barrier. Then we redescribe issues that require attention in the measurement of SAA. It is generally defined that any SAA greater than the detection limit of a quantitative atropine equivalent level (>=1.95 nM in our study) is positive. According to previous studies, SAA is considered to be positive when its atropine equivalent is >=1.95 nM and undetectable when this is <1.95 nM. Nevertheless, as a low SAA can act as AA in the CNS, we should assume that SAA might also be positive if its marker concentration is between 0 and 1.95 nM. In addition, SAA should be measured around 11 a.m. or somewhat later because of the diurnal rhythm of cortisol in humans. PMID- 26138491 TI - Does Anticholinergic Activity Affect Neuropathology? Implication of Neuroinflammation in Alzheimer's Disease. AB - One characteristic neuropathological feature of Alzheimer's disease (AD) is profound neuronal loss in the nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex. Clinically, anticholinergic activity causes a decline in cognitive function and increases the risk of dementia, thus possibly enhancing AD pathologies and neurodegeneration. Until now there has been insufficient human neuropathological data to support this conclusion. Experimental studies using a tauopathy mouse model demonstrated anticholinergics enhanced tau pathology and neurodegeneration corresponding to central anticholinergic activity. Additionally, donepezil, a cholinesterase inhibitor, ameliorated tau pathology and neurodegeneration in the same mouse model. These results indicate the balance between cholinergic and anticholinergic activities might affect neurodegeneration. Importantly, neurodegeneration observed in the mouse model seemed to correspond to the distribution of microglial activation, and it was reported that neuroinflammation plays an important role in the pathomechanism of AD, while anticholinergic activity augments inflammatory responses. Moreover, some studies indicated beta-amyloid itself depletes cholinergic function similarly to anticholinergic activity. Thus, anticholinergic activity might initiate and/or accelerate AD pathology. Limited human data support the conclusion that anticholinergic activity enhances AD related neuropathology and neurodegeneration. However, experimental data from a tauopathy mouse model indicated anticholinergic activity might enhance neurodegeneration with enhanced neuroinflammation including microglial activation. PMID- 26138492 TI - Hypothesis of Endogenous Anticholinergic Activity in Alzheimer's Disease. AB - In this article, we review and repropose our hypothesis of the endogenous appearance of anticholinergic activity (AA) in Alzheimer's disease (AD). First, we introduce our previous articles and speculate that, because acetylcholine (ACh) regulates both cognitive function and inflammation, downregulation of this neurotransmitter causes upregulation of the inflammatory system. AA then appears endogenously with the production of cytokines and the downregulation of ACh in AD. To support our hypothesis, we present a female AD patient whose AA was considered to occur endogenously through her AD pathology. Her serum anticholinergic activity (SAA) was positive at her first visit to our memory clinic, was negative at the 1-year and 2-year follow-up visits, and had become positive again by 3 years. We speculate that the initial positive SAA was related to her AD pathology plus mental stress, and that her SAA at 3 years was related to her AD pathology only. Consequently, we believe that 2 patterns of SAA positivity (and therefore AA) exist. One occurs when the downregulation of ACh reaches a critical level, and the other occurs with the addition of some other factor such as medication, induced illness or mental stress that causes AA to affect AD pathology. Finally, we consider the pharmacotherapy of AD based on the proposed hypothesis and conclude that cholinesterase inhibitors can be used to prevent rapid disease progression, whereas N-methyl-D-aspartate receptor antagonists should be reserved for the treatment of AD that is already in a stage of rapid progression. We also propose a staging schema for patients with AD. PMID- 26138493 TI - Pharmacotherapy for Neurocognitive Disorders Based on the Hypothesis of Endogenous Appearance of Anticholinergic Activity. AB - We previously proposed the hypothesis of endogenous anticholinergic activity (AA) in Alzheimer's disease (AD). According to this hypothesis, the downregulation of acetylcholine seen in AD is associated with upregulation/hyperactivity of N methyl-D-aspartate receptor (NMDAR). The hyperactivation of NMDAR then induces inflammation, which, in turn, causes AA to appear endogenously. Based on this hypothesis, we commented that cholinesterase inhibitors (ChEIs) are 'preventative' therapy for AD and NMDAR antagonists are the true 'treatment' for AD. We also noted that ChEIs, such as donepezil, could treat delirium. Moreover, we proposed measuring serum anticholinergic activity in patients, particularly AD patients, in out-of-hospital pharmacies to monitor the anticholinergic burden for targeted treatment. PMID- 26138494 TI - A Review of the Role of Anticholinergic Activity in Lewy Body Disease and Delirium. AB - We have previously proposed a hypothesis in which we argue that anticholinergic activity (AA) appears endogenously in Alzheimer's disease (AD). Acetylcholine (ACh) controls both cognitive function and inflammation. Consequently, when the downregulation of ACh reaches critical levels, the inflammatory system is upregulated and proinflammatory cytokines with AA appear. However, factors other than downregulation of ACh can produce AA; even if ACh downregulation does not reach critical levels, AA can still appear if one of these other AA-producing factors is added. These factors can include neurocognitive disorders other than AD, such as delirium and Lewy body disease (LBD). In delirium, ACh downregulation fails to reach critical levels, but AA appears due to the use of medicines, physical illnesses or mental stress (termed 'AA inserts'). In LBD, we speculate that AA appears endogenously, even in the absence of severe cognitive dysfunction, for 2 reasons. One reason is that patterns of ACh deterioration are different in LBD from those in AD, with synergistic actions between amyloid and alpha-synuclein thought to cause additional or severe symptoms that accelerate the disease course. The second reason is that AA occurs through disinhibition by reduced cortisol levels that result from severe autonomic parasympathetic dysfunction in LBD. PMID- 26138495 TI - Anticholinergic Activity and Schizophrenia. AB - In this article, we review the downregulation of acetylcholinergic activity in schizophrenia and discuss the similarity and difference between Alzheimer's disease (AD) and schizophrenia in terms of acetylcholine (ACh) and anticholinergic activity (AA); then, we propose the use of cognition-enhancing therapy for schizophrenia. As ACh regulates an inflammatory system, when the cholinergic system is downregulated to a critical level, the inflammatory system is activated. We consider the possibility that AA appears endogenously in AD and accelerates AD pathology. This hypothesis can also be applied to schizophrenia. In fact, even before the onset of the disorder, in the prodromal phase of schizophrenia, cognitive dysfunction exists, and antibodies against astrocyte muscarinic-1 and muscarinic-2 receptors are present in the serum of patients with the paranoid type of schizophrenia. Then we noted that the prodromal phase in schizophrenia might correspond to the mild stage in AD and the acute phase to moderate stage concerning AA. We also think that we should enhance cognition in schizophrenia even in the prodromal phase because as mentioned above, downregulation of ACh is prominent in schizophrenia even in the prodromal phase. PMID- 26138496 TI - Demonstrating the Role of Anticholinergic Activity in a Mood Disorder. AB - We report a case of a 54-year-old woman presenting with amnesia, apathy, work related difficulties and mental stress. At presentation, her Mini-Mental State Examination score was 27 and her serum anticholinergic activity (SAA) was positive without medication or recent physical illnesses. In addition, magnetic resonance imaging revealed mild atrophy of the frontal and temporal lobes, with a relatively intact hippocampus. Consequently, we diagnosed mild cognitive impairment due to Alzheimer's disease and prescribed a cholinesterase inhibitor (donepezil, 10 mg/day); her SAA fully disappeared and clinical symptoms partially resolved. Addition of duloxetine coupled with environmental adjustments caused her cognitive function to return to a normal level, so we diagnosed pseudodementia due to depression. In this case, we believe that the simultaneous cholinergic burden and mental stress led to positive SAA, which made it reasonable to prescribe a cholinesterase inhibitor to ameliorate the associated acetylcholine hypoactivity. We believe that it is essential to recognize the importance of prescribing a cholinesterase inhibitor for specific patients, even those with pseudodementia, to control their clinical symptoms. Moreover, SAA might be a useful biomarker for identifying this subgroup of patients. We propose that anticholinergic activity appears endogenously in mood disorders (depression and bipolar disorder) and set out our rationalization for this hypothesis. PMID- 26138497 TI - Beyond the Hypothesis of Serum Anticholinergic Activity in Alzheimer's Disease: Acetylcholine Neuronal Activity Modulates Brain-Derived Neurotrophic Factor Production and Inflammation in the Brain. AB - The brain of Alzheimer's disease (AD) patients is characterized by neurodegeneration, especially an acetylcholine (ACh) neuronal deficit with accumulation of beta-amyloid protein, which leads to oxygen stress and inflammation. The active oxygen directly damages the neuron by increasing intracellular Ca(2+). The inflammation is due to activation of the microglia, thereby producing cytokines which inhibit the production of brain-derived neurotrophic factor (BDNF). As the BDNF acts by neuronal protection, synaptogenesis and neurogenesis, the reduction of BDNF in the brain of AD patients worsens the symptoms of AD. On the other hand, treatment of AD patients with a cholinesterase inhibitor enhances ACh activity and inhibits inflammation. Then the expression of BDNF is restored and neuroprotection reestablished. However, there are several reports which showed controversial results concerning the relationship between BDNF and AD. We speculate that BDNF is related to some neurocognitive process and reflects neuronal activity in other neurodegenerative and neuropsychiatric disorders and that in the mild cognitive impairment stage, BDNF and choline acetyltransferase (ChAT) activities are hyperactivated because of a compensatory mechanism of AD pathology. In contrast, in the mild stage of AD, BDNF and ChAT activity are downregulated. PMID- 26138498 TI - Plasma Cholinesterase Activity in Alzheimer's Disease. AB - Cholinesterase inhibitors (ChEIs) are not allowed to be prescribed in combination, which means that we need to select 1 of 3 ChEIs for use in a patient with Alzheimer's disease (AD). However, there is no quantitative analysis on the differences between these agents. In this article, we propose that plasma cholinesterase activity (pChE) could be used as the standard for differentiating between rivastigmine (Riv) and donepezil (Don) in the management of AD. To date, we have treated 6 patients with Riv 18 mg and 5 patients with Don 5 mg. The pChE is related to low-grade inflammation associated with AD, diabetes mellitus and lipid metabolic dysfunction. Moreover, low pChE is related to liver dysfunction. The pChE must be kept under control. We speculated that Riv is the most appropriate therapy for patients with relatively high pChE, whereas Don is best reserved for those AD patients with relatively low pChE. PMID- 26138500 TI - Electronic coupling between ligand and core energy states in dithiolate monothiolate stabilized Au clusters. AB - Electron transfer activities of metal clusters are fundamentally significant and have promising potential in catalysis, charge or energy storage, sensing, biomedicine and other applications. Strong resonance coupling between the metal core energy states and the ligand molecular orbitals has not been established experimentally, albeit exciting progress has been achieved in the composition and structure determination of these types of nanomaterials recently. In this report, the coupling between core and ligand energy states is demonstrated by the rich electron transfer activities of Au130 clusters. Quantized electron transfers to the core and multi-electron transfers involving the durene-dithiolate ligands were observed at lower and higher potentials, respectively, in voltammetric studies. After a facile multi-electron oxidation from +1.34 to +1.40 V, several reversal reduction processes at more negative potentials, i.e. +0.91 V, +0.18 V and -0.34 V, were observed in an electrochemically irreversible fashion or with sluggish kinetics. The number of electrons and the shifts of the respective reduction potentials in the reversal process were attributed to the electronic coupling or energy relaxation processes. The electron transfer activities and subsequent relaxation processes are drastically reduced at lower temperatures. The time- and temperature-dependent relaxation, involving multiple energy states in the reversal reduction processes upon the oxidation of ligands, reveals the coupling between core and ligand energy states. PMID- 26138499 TI - SLC1A4 mutations cause a novel disorder of intellectual disability, progressive microcephaly, spasticity and thin corpus callosum. AB - Two unrelated patients, presenting with significant global developmental delay, severe progressive microcephaly, seizures, spasticity and thin corpus callosum (CC) underwent trio whole-exome sequencing. No candidate variant was found in any known genes related to the phenotype. However, crossing the data of the patients illustrated that they both manifested pathogenic variants in the SLC1A4 gene which codes the ASCT1 transporter of serine and other neutral amino acids. The Ashkenazi patient is homozygous for a deleterious missense c.766G>A, p.(E256K) mutation whereas the Ashkenazi-Iraqi patient is compound heterozygous for this mutation and a nonsense c.945delTT, p.(Leu315Hisfs*42) mutation. Structural prediction demonstrates truncation of significant portion of the protein by the nonsense mutation and speculates functional disruption by the missense mutation. Both mutations are extremely rare in general population databases, however, the missense mutation was found in heterozygous mode in 1:100 Jewish Ashkenazi controls suggesting a higher carrier rate among Ashkenazi Jews. We conclude that SLC1A4 is the disease causing gene of a novel neurologic disorder manifesting with significant intellectual disability, severe postnatal microcephaly, spasticity and thin CC. The role of SLC1A4 in the serine transport from astrocytes to neurons suggests a possible pathomechanism for this disease and implies a potential therapeutic approach. PMID- 26138501 TI - Effect of Pulse Rate and Polarity on the Sensitivity of Auditory Brainstem and Cochlear Implant Users to Electrical Stimulation. AB - To further understand the response of the human brainstem to electrical stimulation, a series of experiments compared the effect of pulse rate and polarity on detection thresholds between auditory brainstem implant (ABI) and cochlear implant (CI) patients. Experiment 1 showed that for 400-ms pulse trains, ABI users' thresholds dropped by about 2 dB as pulse rate was increased from 71 to 500 pps, but only by an average of 0.6 dB as rate was increased further to 3500 pps. This latter decrease was much smaller than the 7.7-dB observed for CI users. A similar result was obtained for pulse trains with a 40-ms duration. Furthermore, experiment 2 showed that the threshold difference between 500- and 3500-pps pulse trains remained much smaller for ABI than for CI users, even for durations as short as 2 ms, indicating the effect of a fast-acting mechanism. Experiment 3 showed that ABI users' thresholds were lower for alternating polarity than for fixed-polarity pulse trains, and that this difference was greater at 3500 pps than at 500 pps, consistent with the effect of pulse rate on ABI users' thresholds being influenced by charge interactions between successive biphasic pulses. Experiment 4 compared thresholds and loudness between trains of asymmetric pulses of opposite polarity, in monopolar mode, and showed that in both cases less current was needed when the anodic, rather than the cathodic, current was concentrated into a short time interval. This finding is similar to that previously observed for CI users and is consistent with ABI users being more sensitive to anodic than cathodic current. We argue that our results constrain potential explanations for the differences in the perception of electrical stimulation by CI and ABI users, and have potential implications for future ABI stimulation strategies. PMID- 26138502 TI - Temporal Dietary Patterns Derived among the Adult Participants of the National Health and Nutrition Examination Survey 1999-2004 Are Associated with Diet Quality. AB - BACKGROUND: Temporal dietary patterns, the distribution of energy or nutrient intakes observed over a period of time, is an emerging area of dietary patterns research that incorporates time of dietary intake with frequency and amount of intake to determine population clusters that may have similar characteristics or outcomes related to diet quality. OBJECTIVE: We examined whether differences in diet quality were present between clusters of individuals with similar daily temporal dietary patterns. DESIGN: The first-day 24-hour dietary recall data from the cross-sectional National Health and Nutrition Examination Survey, 1999-2004, were used to determine proportional energy intake, time of intake, frequency of intake occasions, and mean diet quality. PARTICIPANTS/SETTING: Data from 9,326 US adults aged 20 to 65 years were included. STATISTICAL ANALYSES PERFORMED: The mean diet quality, classified by the Healthy Eating Index-2005, of participant clusters with similar temporal dietary patterns derived on the basis of individual proportional energy intake, time of intake, and frequency of intake, were inferentially compared using multiple linear regression that controlled for potential confounders and other covariates (P<0.05/6). RESULTS: Diet quality differences were present between US population clusters exhibiting similar daily temporal dietary patterns (P<0.001 with one exception, which was P=0.08). Participant characteristics of race/ethnicity, age, household poverty-income ratio, and body mass index were associated with the temporal dietary patterns. The cluster representing the temporal dietary pattern with proportionally equivalent energy consumed during three evenly spaced eating occasions had a significantly greater mean total Healthy Eating Index-2005 score compared with the other temporal dietary pattern clusters. CONCLUSIONS: Temporal dietary patterns are associated with differences in US adult daily diet quality, demonstrating that elements beyond food and nutrient intake, such as time, can be incorporated with dietary patterns to determine links to diet quality that enhance knowledge of the complicated interplay of time and dietary patterns. PMID- 26138503 TI - Muscular anatomy of an entoproct creeping-type larva reveals extraordinary high complexity and potential shared characters with mollusks. AB - BACKGROUND: Entoprocta (Kamptozoa) is an enigmatic, acoelomate, tentacle-bearing phylum with indirect development, either via a swimming- or a creeping-type larva and still debated phylogenetic position within Lophotrochozoa. Recent morphological and neuro-anatomical studies on the creeping-type larva support a close relationship of Entoprocta and Mollusca, with a number of shared apomorphies including a tetraneurous nervous system and a complex serotonin expressing apical organ. However, many morphological traits of entoproct larvae, in particular of the putative basal creeping-type larva, remain elusive. RESULTS: Applying fluorescent markers and 3D modeling, we found that this larval type has the most complex musculature hitherto described for any lophotrochozoan larva. The muscle systems identified include numerous novel and most likely creeping type larva-specific structures such as frontal organ retractors, several other muscle fibers originating from the frontal organ, and longitudinal prototroch muscles. Interestingly, we found distinct muscle sets that are also present in several mollusks. These include paired sets of dorso-ventral muscles that intercross ventrally above the foot sole and a paired enrolling muscle that is distinct from the musculature of the body wall. CONCLUSION: Our data add further morphological support for an entoproct-mollusk relationship (Tetraneuralia) and strongly argue for the presence of an enrolling musculature as well as seriality (but not segmentation) in the last common tetraneuralian ancestor. The evolutionary driving forces that have led to the emergence of the extraordinarily complex muscular architecture in this short-lived, non-feeding entoproct larval type remain unknown, as are the processes that give rise to the highly different and much simpler muscular bodyplan of the adult entoproct during metamorphosis. PMID- 26138504 TI - Connectivity-based segmentation of the periaqueductal gray matter in human with brainstem optimized diffusion MRI. AB - The periaqueductal gray matter (PAG) is a midbrain structure, involved in key homeostatic neurobiological functions, such as pain modulation and cardiorespiratory control. Animal research has identified four subdivisional columns that differ in both connectivity and function. Until now these findings have not been replicated in humans. This study used high-resolution brainstem optimized diffusion magnetic resonance imaging and probabilistic tractography to segment the human PAG into four subdivisions, based on voxel connectivity profiles. We identified four distinct subdivisions demonstrating high spatial concordance with the columns of the animal model. The resolution of these subdivisions for individual subjects permitted detailed examination of their structural connectivity without the requirement of an a priori starting location. Interestingly patterns of forebrain connectivity appear to be different to those found in nonhuman studies, whereas midbrain and hindbrain connectivity appears to be maintained. Although there are similarities in the columnar structure of the PAG subdivisions between humans and nonhuman animals, there appears to be different patterns of cortical connectivity. This suggests that the functional organization of the PAG may be different between species, and as a consequence, functional studies in nonhumans may not be directly translatable to humans. This highlights the need for focused functional studies in humans. PMID- 26138505 TI - Dimeric TADDOL Phosphoramidites in Asymmetric Catalysis: Domino Deracemization and Cyclopropanation of Sulfonium Ylides. AB - A gold-catalyzed asymmetric cyclopropanation of unactivated olefins with sulfonium ylides in the presence of a bimetallic catalyst with a novel dimeric TADDOL-phosphoramidite ligand is reported. This transformation allows a rare gold catalyzed dynamic deracemization of chiral racemic substrates, where the same catalyst is responsible for several synergistic tasks in solution. The products are useful building blocks in synthesis and enable expeditious access to natural products. PMID- 26138506 TI - Fasting induced kisspeptin signaling suppression is regulated by glutamate mediated cues in adult male rhesus macaque (Macaca mulatta). AB - Kisspeptin signaling is suppressed by short term fasting. It has been reported that hypothalamic Kiss1 and Kiss1r mRNA expression decreased after 48h of fasting in male rhesus monkey. But the mechanism involved in the reduction of kisspeptin signaling after 48h of fasting is unknown. Recent studies have suggested the role of afferent excitatory and inhibitory pathways in the regulation of kisspeptin neurons. Therefore, this study was designed to observe the changes in the glutamate and GABA signaling during fed and 48h fasting states by performing immunofluorescence to examine the interaction of kisspeptin neurons with NR1 subunit of NMDA receptors and by performing SYBR green qRT-PCR to measure and quantify the levels of Kiss1, Kiss1r, NR1 and GAD67 mRNA in the POA and MBH of adult male rhesus macaque (Macaca mulatta) during 48h of fasting (n=2) and fed ad libitum (n=2). Plasma testosterone (p<0.05) and blood glucose levels were significantly (p<0.001) decreased after short term fasting. Our results clearly showed that expression of hypothalamic Kiss1, Kiss1r and NR1 mRNA was significantly (p<0.05) reduced in adult male rhesus monkeys which were fasted for 48h as compared to those which were fed ad libitum. There was no clear difference in the GAD67 mRNA contents between the two groups. Number of kisspeptin neurons and the interactions of kisspeptin neurons with NR1 were significantly (p<0.05) reduced after 48h fasting. These observations suggest that decreased kisspeptin signaling during fasting may occur due to reduction in glutamatergic inputs to kisspeptin neurons. Our results also suggest that fasting induced suppression of kisspeptin signaling is not mediated through GABAergic neurons. PMID- 26138507 TI - Ghrelin counteracts insulin-induced activation of vagal afferent neurons via growth hormone secretagogue receptor. AB - Vagal afferent nerves sense meal-related gastrointestinal and pancreatic hormones and convey their information to the brain, thereby regulating brain functions including feeding. We have recently demonstrated that postprandial insulin directly acts on the vagal afferent neurons. Plasma concentrations of orexigenic ghrelin and anorexigenic insulin show reciprocal dynamics before and after meals. The present study examined interactive effects of ghrelin and insulin on vagal afferent nerves. Cytosolic Ca(2+) concentration ([Ca(2+)]i) in isolated nodose ganglion (NG) neurons was measured to monitor their activity. Insulin at 10(-7)M increased [Ca(2+)]i in NG neurons, and the insulin-induced [Ca(2+)]i increase was inhibited by treatment with ghrelin at 10(-8)M. This inhibitory effect of ghrelin was attenuated by [D-Lys(3)]-GHRP-6, an antagonist of growth hormone-secretagogue receptor (GHSR). Des-acyl ghrelin had little effect on insulin-induced [Ca(2+)]i increases in NG neurons. Ghrelin did not affect [Ca(2+)]i increases in response to cholecystokinin (CCK), a hormone that inhibits feeding via vagal afferent neurons, indicating that ghrelin selectively counteracts the insulin action. These results demonstrate that ghrelin via GHSR suppresses insulin-induced activation of NG neurons. The action of ghrelin to counteract insulin effects on NG might serve to efficiently inform the brain of the systemic change between fasting-associated ghrelin-dominant and fed-associated insulin-dominant states for the homeostatic central regulation of feeding and metabolism. PMID- 26138509 TI - Mesenteric-Based Surgery Exploits Gastrointestinal, Peritoneal, Mesenteric and Fascial Continuity from Duodenojejunal Flexure to the Anorectal Junction--A Review. AB - INTRODUCTION: It is now well established that mesenteric-based colorectal surgery is associated with superior outcomes. Recent anatomic observations have demonstrated that the mesenteric organ is contiguous from the duodenojejunal to the anorectal junction. This led to similar observations in relation to associated peritoneum and fascia. The aim of this review was to demonstrate the relevance of the contiguity principle to resectional colorectal surgery. METHODS: All literature in relation to mesenteric anatomy was reviewed from 1873 to the present, without language restriction. RESULTS: Mesenteric-based surgery (i.e. complete mesocolic excision, total mesocolic and mesorectal excision) requires division of the peritoneal reflection (i.e. peritonotomy), and mesenteric mobilisation in the mesofascial plane. These are the fundamental technical elements of mesenterectomy. Mesenteric, peritoneal and fascial contiguity mean that in resectional surgery, these technical elements can be reproducibly applied at all levels from the origin at the superior mesenteric root, to the anorectal junction. CONCLUSIONS: The goals of complete mesocolic, total mesocolic and mesorectal excision can be universally achieved at any level from duodenojejunal flexure to anorectal junction, by adopting technical elements based on mesenteric, peritoneal and fascial contiguity. PMID- 26138508 TI - Prevalence of non-alcoholic fatty liver disease in four different weight related patient groups: association with small bowel length and risk factors. AB - BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an obesity associated common cause of liver inflammation and there are concerns that it may turn out to be the most common cause of liver failure as prevalence of obesity increases. We determined the prevalence of NASH in relation to gender and body mass index (BMI). Furthermore, we assessed the association of NASH with the length of the small bowel. METHODS: 124 liver samples obtained during routine operations were examined looking for NAFLD Activity Score (nonalcoholic fatty liver disease). The length of small bowel was measured intraoperatively. For evaluation, patients were divided into four groups according to their BMI (group 1: normal weight, group 2: overweight, group 3: grade I/II morbidly obese, and group 4 grade III morbidly obese patients). RESULTS: BMI showed a strong positive correlation with risk of NASH and a weak positive correlation with small bowel length. No normal weight patient was at risk of NASH, whereas in group 2 14% had uncertain and 32% definite NASH. In group 3 11% had uncertain and 27% definite NASH. In group 4 nearly two-thirds were classified as uncertain or definite NASH. Median length of small bowel in all patients was 450 cm (range 226-860 cm). Within group 4, patients with definite/uncertain NASH had a longer small bowel than patients without NASH. CONCLUSIONS: Prevalence of NASH is high in morbidly obese. Small bowel length could influence the complex etiology of the disease. PMID- 26138510 TI - Flexible indium-gallium-zinc-oxide Schottky diode operating beyond 2.45 GHz. AB - Mechanically flexible mobile phones have been long anticipated due to the rapid development of thin-film electronics in the last couple of decades. However, to date, no such phone has been developed, largely due to a lack of flexible electronic components that are fast enough for the required wireless communications, in particular the speed-demanding front-end rectifiers. Here Schottky diodes based on amorphous indium-gallium-zinc-oxide (IGZO) are fabricated on flexible plastic substrates. Using suitable radio-frequency mesa structures, a range of IGZO thicknesses and diode sizes have been studied. The results have revealed an unexpected dependence of the diode speed on the IGZO thickness. The findings enable the best optimized flexible diodes to reach 6.3 GHz at zero bias, which is beyond the critical benchmark speed of 2.45 GHz to satisfy the principal frequency bands of smart phones such as those for cellular communication, Bluetooth, Wi-Fi and global satellite positioning. PMID- 26138511 TI - Towards experimental quantum-field tomography with ultracold atoms. AB - The experimental realization of large-scale many-body systems in atomic-optical architectures has seen immense progress in recent years, rendering full tomography tools for state identification inefficient, especially for continuous systems. To work with these emerging physical platforms, new technologies for state identification are required. Here we present first steps towards efficient experimental quantum-field tomography. Our procedure is based on the continuous analogues of matrix-product states, ubiquitous in condensed-matter theory. These states naturally incorporate the locality present in realistic physical settings and are thus prime candidates for describing the physics of locally interacting quantum fields. To experimentally demonstrate the power of our procedure, we quench a one-dimensional Bose gas by a transversal split and use our method for a partial quantum-field reconstruction of the far-from-equilibrium states of this system. We expect our technique to play an important role in future studies of continuous quantum many-body systems. PMID- 26138512 TI - High metabolic N-oxidation of voriconazole in a patient with refractory aspergillosis and CYP2C19*17/*17 genotype. PMID- 26138513 TI - Clinical use of GLP-1 agonists and DPP4 inhibitors. AB - Type 2 diabetes is a growing problem, with 387 million people currently affected, and 592 million by 2035. Whilst diet and exercise are the corner stones of treatment, oral hypoglycaemic agents are often needed to achieve glycaemic control, thereby reducing the chance of long term diabetic complications. Biguanides and sulfonylureas have been the standard tablets used for this disorder, until 2005-7 when glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP4) inhibitors became available. Their major advantage over sulfonylureas is that they are weight lowering or weight neutral, and have a very low incidence of hypoglycaemia. GLP-1 agonists are injectables, whereas the DPP4 inhibitors are administered orally. Both agents are best used in combination with other hypoglycaemic medication, especially metformin and sodium glucose co transporter 2 (SGLT2) inhibtors. Usage is increasing, being roughly equal to that of sulfonylureas, but less than that of metformin. Side effects appear to be minimal. PMID- 26138514 TI - Beyond conventional chemotherapy: Emerging molecular targeted and immunotherapy strategies in urothelial carcinoma. AB - Advanced urothelial carcinoma is frequently lethal, and improvements in cytotoxic chemotherapy have plateaued. Recent technological advances allows for a comprehensive analysis of genomic alterations in a timely manner. The Cancer Genome Atlas (TCGA) study revealed that there are numerous genomic aberrations in muscle-invasive urothelial carcinoma, such as TP53, ARID1A, PIK3CA, ERCC2, FGFR3, and HER2. Molecular targeted therapies against similar genetic alterations are currently available for other malignancies, but their efficacy in urothelial carcinoma has not been established. This review describes the genomic landscape of malignant urothelial carcinomas, with an emphasis on the potential to prosecute these tumours by deploying novel targeted agents and immunotherapy in appropriately selected patient populations. PMID- 26138515 TI - PI3K/Akt/mTOR: A promising therapeutic target for non-medullary thyroid carcinoma. AB - Thyroid carcinoma (TC) is the most common endocrine malignancy. The pathogenesis of TC is complex and involves multiple genetic events that lead to activation of oncogenic pathways such as the MAP kinase (MAPK) pathway and the PI3K/Akt/mTOR pathway. The PI3K/Akt pathway has emerged as an important player in the pathogenesis of TC, particularly in follicular and advanced anaplastic or poorly differentiated TC. Because these patients have a poor prognosis, particularly when their tumors become resistant to the conventional treatment with radioactive iodine, efforts have been made to identify possible targets for therapy within these pathways. Orally available drugs targeting the PI3K/Akt/mTOR pathway are being used with success in treatment of several types of malignant tumors. There is an increasing amount of preclinical and clinical data supporting that this pathway may represent a promising target for systemic therapy in TC. The present review focuses on the most recent developments on the role of the PI3K/Akt pathway in the pathogenesis of non-medullary TC and will provide insight into how this pathway can be targeted either alone or in the context of multimodal therapeutic strategies for treatment of advanced TC. PMID- 26138516 TI - Does Computer Assisted Navigation Improve Functional Outcomes and Implant Survivability after Total Knee Arthroplasty? AB - The objective of this study was to determine whether computer assisted navigation in total knee arthroplasty (TKA) improves functional outcomes and implant survivability using data from a large national database. We analysed 9054 primary TKA procedures performed between 2006 and 2012 from the New Zealand National Joint Registry. Functional outcomes were assessed using Oxford Knee Questionnaires at six months and five years. On multivariate analysis, there was no significant difference in mean Oxford Knee Scores between the navigated and non-navigated groups at six months (39.0 vs 38.1, P=0.54) or five years (42.2 vs 42.0, P=0.76). At current follow-up, there was no difference in revision rates between navigated and non-navigated TKA (0.46 vs 0.43 revisions 100 component years, P=0.8). PMID- 26138517 TI - The selective dopamine D3 receptor antagonist SB-277011A significantly accelerates extinction to environmental cues associated with cocaine-induced place preference in male Sprague-Dawley rats. PMID- 26138518 TI - Implementation of central venous catheter bundle in an intensive care unit in Kuwait: Effect on central line-associated bloodstream infections. AB - Central line-associated bloodstream infection (CLABSIs) is an important healthcare-associated infection in the critical care units. It causes substantial morbidity, mortality and incurs high costs. The use of central venous line (CVL) insertion bundle has been shown to decrease the incidence of CLABSIs. Our aim was to study the impact of CVL insertion bundle on incidence of CLABSI and study the causative microbial agents in an intensive care unit in Kuwait. Surveillance for CLABSI was conducted by trained infection control team using National Health Safety Network (NHSN) case definitions and device days measurement methods. During the intervention period, nursing staff used central line care bundle consisting of (1) hand hygiene by inserter (2) maximal barrier precautions upon insertion by the physician inserting the catheter and sterile drape from head to toe to the patient (3) use of a 2% chlorohexidine gluconate (CHG) in 70% ethanol scrub for the insertion site (4) optimum catheter site selection. (5) Examination of the daily necessity of the central line. During the pre-intervention period, there were 5367 documented catheter-days and 80 CLABSIs, for an incidence density of 14.9 CLABSIs per 1000 catheter-days. After implementation of the interventions, there were 5052 catheter-days and 56 CLABSIs, for an incidence density of 11.08 per 1000 catheter-days. The reduction in the CLABSI/1000 catheter days was not statistically significant (P=0.0859). This study demonstrates that implementation of a central venous catheter post-insertion care bundle was associated with a reduction in CLABSI in an intensive care area setting. PMID- 26138519 TI - Premaxillary osteotomy fixation in bilateral cleft lip/palate: Introducing a new technique. AB - OBJECTIVES: In bilateral cleft lip/palate patients, sometimes the premaxilla is severely protruded and twisted. In such situations premaxillary osteotomy is beneficial. In this article a new technique for fixation of premaxilla after osteotomy is presented. METHODS: The lip-split approach and premaxillary osteotomy and ostectomy from bony nasal septum were carried out. Fixation of osteotomized premaxilla was achieved with low profile miniplate or microplate. Bone grafting of that side was performed during the same session. RESULTS: This procedure was performed in three patients, with good labial repair after the lip split. The bone graft was successful in all the three cases and there were no complication for premaxillary osteotomy in this series. CONCLUSION: In protruding premaxilla, osteotomy and fixation of premaxilla with miniplate to the vomer bone during alveolar bone grafting through a lip-split approach yielded satisfactory results in patients requiring secondary functional cheilorhinoplasty. PMID- 26138520 TI - Risk factors for postoperative complications in patients on maintenance hemodialysis who undergo abdominal surgery. AB - BACKGROUND/OBJECTIVE: Patients on hemodialysis (HD) who undergo abdominal surgery for gastrointestinal disease are at increased risk of postoperative complications. In this study, we retrospectively investigated the predictors of postoperative complications among such patients. METHODS: The study group comprised 36 HD patients who underwent abdominal surgery for gastrointestinal disease between 2003 and 2012. The clinicopathological factors of the patients who did and did not suffer postoperative complications were compared. RESULTS: The overall morbidity and mortality rates were 39% (14/36) and 14% (5/36), respectively. Physical status according to the American Society of Anesthesiologists (ASA) classification (p = 0.0203) and intraoperative blood loss (p = 0.0013) were found to differ significantly between the groups. CONCLUSION: The morbidity and mortality rates of HD patients who underwent abdominal surgery for gastrointestinal disease were high. Physical status according to the ASA classification and intraoperative blood loss were found to be associated with postoperative complications. Therefore, patients with comorbidities, such as heart disease and diabetes mellitus, have to be treated appropriately before surgery. In addition, it is important that surgeons perform operations carefully and avoid excessive blood loss. PMID- 26138521 TI - Comparison of modified Limberg flap transposition and lateral advancement flap transposition with Burow's triangle in the treatment of pilonidal sinus disease. AB - BACKGROUND: Although many options exist for surgical treatment of pilonidal sinus disease (PSD), consensus has not yet been achieved, as all surgical methods have various rates of complications, postoperative infection, and recurrence. METHODS: This study was a prospective, randomized, clinical trial, and was conducted with consecutive 100 patients admitted to Ankara Military Hospital General Surgery Service for treatment of PSD from May 2013 to August 2013. This study compared two surgical treatments for PSD: modified Limberg flap transposition and lateral advancement flap transposition with Burow's triangle. The patients received surgical treatment with either modified Limberg flap transposition (n = 50) or lateral advancement flap transposition with Burow's triangle (n = 50). Clinical healing period, length of hospital stay, operative time, postoperative complications including recurrence, wound dehiscence, and surgical site infection, as noted during postoperative follow-up period; Visual Analog Scale scores for pain. RESULTS: The mean follow-up period was 12 months. No significant differences were observed between the 2 groups in length of hospital stay (P = .515), operative time (P = .175), wound dehiscence (P = .645), and Visual Analog Scale pain scores (P = .112). The mean operative times were 42.5 minutes in the modified Limberg group and 40.0 minutes in the lateral advancement group. CONCLUSIONS: Although lateral advancement flap transposition with Burow's triangle is used less often than modified Limberg flap transposition, we could not determine a parameter that was statistically different such as operative time, postoperative complication, or the length of hospital stay. Hence, the lateral advancement flap is as viable an option as other more preferable techniques in the treatment of PSD, which particularly settled on the upper segment without a deep natal cleft. PMID- 26138522 TI - Caring for the surgically anxious patient: a review of the interventions and a guide to optimizing surgical outcomes. AB - BACKGROUND: Preoperative surgical anxiety is an unpleasant and common reaction exhibited by patients who are scheduled for surgical procedures. Beyond emotional effects on the patient, it can also have negative repercussions on the surgery including longer hospital stays and poorer outcomes. Given the widespread impacts of preoperative anxiety, it is critical for surgeons to gain a better understanding of how to identify and reduce surgical anxiety in their patients. DATA SOURCES: This study used the PubMed database to review the current literature to evaluate screening tools and interventions for surgically anxious patients. CONCLUSIONS: Psychiatric anxiety surveys are currently the most appropriate form of assessment for surgical anxiety. Patient education is important for preventing and reducing anxiety levels in patients. Both nonpharmacological and pharmacological interventions have been shown to be effective in reducing patient anxiety and treatment should be based on patient preference, resources available, and the surgeon's experience. PMID- 26138523 TI - Too much knowledge for a nurse? Use of physical assessment by final-semester nursing students. AB - There is debate around the scope of physical assessment skills that should be taught in undergraduate nursing programs. Yet this debate is largely uninformed by evidence on what is learned and practiced by nursing students. This study examined the pattern and correlates of physical assessment skill utilization by 208 graduating nursing students at an Australian university, including measures of knowledge, frequency of use, and perceived barriers to physical assessment skills during clinical practice. Of the 126 skills surveyed, on average, only five were used every time students practiced. Core skills reflected inspection or general observation of the patient; none involved complex palpation, percussion, or auscultation. Skill utilization was also shaped by specialty area. Most skills (70%) were, on average, never performed or learned and students perceived nursing physical assessment was marginalized in both university and workplace contexts. Lack of confidence was, thus, a significant barrier to use of skills. Based on these findings, we argue that the current debate must shift to how we might best support students to integrate comprehensive physical assessment into nursing practice. PMID- 26138524 TI - Arginine-rich histones have strong antiviral activity for influenza A viruses. AB - While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular traps, where they play an important role in NET-mediated antimicrobial killing. Here, we show anti-influenza activity of histones against both seasonal H3N2 and H1N1, but not pandemic H1N1. The arginine rich histones, H3 and H4, had greater neutralizing and viral aggregating activity than the lysine rich histones, H2A and H2B. Of all core histones, histone H4 is most potent in neutralizing IAV, and incubation with IAV with histone H4 results in a decrease in uptake and viral replication by epithelial cells when measured by qRT PCR. The antiviral activity of histone H4 is mediated principally by direct effects on viral particles. Histone H4 binds to IAV as assessed by ELISA and co sedimentation of H4 with IAV. H4 also induces aggregation, as assessed by confocal microscopy and light transmission assays. Despite strong antiviral activity against the seasonal IAV strains, H4 was inactive against pandemic H1N1. These findings indicate a possible role for histones in the innate immune response against IAV. PMID- 26138525 TI - Enterococcus faecalis promotes osteoclastogenesis and semaphorin 4D expression. AB - Enterococcus faecalis is considered a major bacterial pathogen implicated in endodontic infections and contributes considerably to periapical periodontitis. This study aimed to investigate the potential mechanisms by which E. faecalis accounts for the bone destruction in periapical periodontitis in vitro. Osteoclast precursor RAW264.7 cells were treated with E. faecalis ATCC 29212 and a wild strain of E. faecalis derived clinically from an infected root canal. The results showed that, to some extent, E. faecalis induced the RAW264.7 cells to form tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclast-like cells. This pathogen markedly stimulated RAW264.7 cells to express semaphorin 4D (Sema4D), which inhibits bone formation. Once RAW264.7 cells were primed by low-dose receptor activator of nuclear factor-kappa B ligand (RANKL), E. faecalis could significantly increase the production of TRAP-positive multinucleated cells and up-regulate the expression of osteoclast-specific markers, including NFATc1, TRAP and cathepsin K. Both p38 and ERK1/2 MAPK signaling pathways were activated by E. faecalis in RANKL-primed RAW264.7 cells, and meanwhile the expression of Sema4D was highly increased. In conclusion, E. faecalis may greatly contribute to the bone resorption in periapical periodontitis by promoting RANKL-dependent osteoclastogenesis and expression of Sema4D through activation of p38 and ERK1/2 MAPK signaling pathways. PMID- 26138526 TI - Review of assessment tools for psychotic-like experiences misses the psychosis like symptoms semi-structured interview (PLIKSi) in ALSPAC. PMID- 26138527 TI - Hepatotoxicity of New Oral Anticoagulants (NOACs). AB - Case reports and analyses of clinical studies and of pharmacovigilance data suggest that new oral anticoagulants (NOACs) are associated with a small risk for hepatotoxicity. The objective of this publication is to summarize the current data about this subject, with a special emphasis on pharmacovigilance data in the World Health Organization (WHO) Global Individual Case Safety Reports (ICSR) database and on potential mechanisms of hepatotoxicity. For that, all available case reports as well as published analyses of clinical studies were obtained with a detailed search in PubMed. In addition, pharmacovigilance data from VigiBase((r)), the WHO Global ICRS database, were extracted and analyzed. The data show that liver injury associated with NOACs was reported in clinical studies and in pharmacovigilance databases. Several case reports described potentially life-threatening hepatotoxicity in patients treated with rivaroxaban or dabigatran. For rivaroxaban, most affected patients were symptomatic and liver injury was most often hepatocellular or mixed. The frequency was between 0.1 and 1 % in clinical studies and was by trend lower than for comparators (mostly enoxaparin or warfarin). Comparing the pharmacovigilance reports for the individual NOACs, more hepatic adverse events were reported for rivaroxaban than for dabigatran or apixaban. With the exception of edoxaban, for which only few reports are available, patients with acute liver failure have been reported for every NOAC, but most patients had concomitant drugs or diseases. So far, there are no clear mechanisms explaining the hepatotoxicity of these drugs. We conclude that hepatotoxicity appears to be associated with all NOACs currently on the market. Hepatotoxicity associated with NOACs is idiosyncratic; it appears at therapeutic doses, is rare and the mechanism is not related to the pharmacological action of these drugs. Prescribers should inform patients about possible symptoms of hepatotoxicity and stop these drugs in patients presenting with severe liver injury. PMID- 26138528 TI - [Isolated left abducens nerve palsy secondary to Lyme disease in an 11-year-old boy]. PMID- 26138529 TI - [Spontaneous bilateral dislocation of the crystalline lens in the case of a patient with homocystinuria, with anterior chamber OCT showing endothelial damage]. PMID- 26138530 TI - Visual snow: Report of three cases. PMID- 26138531 TI - Association of variants in CCR6 with susceptibility to lupus nephritis in Chinese. PMID- 26138532 TI - Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study. AB - Stem cell strategies focused on replacement of RPE cells for the treatment of geographic atrophy are under intense investigation. Although the eye has long been considered immune privileged, there is limited information about the immune response to transplanted cells in the subretinal space of large animals. The purpose of this study was to evaluate the survival of allogenic induced pluripotent stem cell-derived RPE cells (iPSC-RPE) delivered to the subretinal space of the pig as well as determine whether these cells induce an immune response in non-diseased eyes. GFP positive iPSC-RPE, generated from outbred domestic swine, were injected into the subretinal space of vitrectomized miniature swine. Control eyes received vehicle only. GFP positive iPSC-RPE cells were identified in the subretinal space 3 weeks after injection in 5 of 6 eyes. Accompanying GFP-negative cells positive for IgG, CD45 and macrophage markers were also identified in close proximity to the injected iPSC-RPE cells. All subretinal cells were negative for GFAP as well as cell cycle markers. We found that subretinal injection of allogenic iPSC-RPE cells into wild-type mini-pigs can induce the innate immune response. These findings suggest that immunologically matched or autologous donor cells should be considered for clinical RPE cell replacement. PMID- 26138533 TI - [Nondermatophytic and noncandidal fungi isolated in Le Dantec University hospital of Dakar in 2014: Epidemiological, clinical and mycological study]. AB - In recent years, the incidence of superficial fungal infections involving nondermatophytic and noncandidal fungi increased considerably. The objective of this work was to analyze the epidemiological, clinical and mycological fungal infections due to nondermatophytic and noncandidal fungi diagnosed in the laboratory of parasitology-mycology of Le Dantec hospital in Dakar. With a retrospective study of the various cases of nondermatophytic and noncandidal fungi isolated in the laboratory of parasitology-mycology during the period of November 2013 to December 2014, we collected 22 cases of infections in 11 men and 11 women; age ranging from 17 to 75 years with a mean of 45.3 years (sex ratio=1): eight cases of intertrigo, seven cases of onychomycosis, four cases of palmoplantar keratoderma (KPP), a case of onychomycosis associated with interdigital intertrigo, a case of infectious myositis and one case of African histoplasmosis. We have isolated and identified a total of 22 nondermatophytic and noncandidal fungi: ten Fusarium, five Trichosporon, two Chrysosporium, two Geotrichum, one Rhodotorula, one Neoscytalidium dimidiatum and one Histoplasma capsulatum var. duboisii. So we are seeing the emergence of nondermatophytic and noncandidal increasingly isolated from superficial and local lesions. These fungi, generally contaminants or commensal, cause a problem regarding their direct involvement in pathological processes in which they are isolated. So we should respect the recommendations proposed for their involvement in pathological processes and, by a collaboration between clinician and biologist, demonstrate their real involvement through effective, targeted treatment. PMID- 26138534 TI - Clonal hematopoiesis: a "CHIP" off the old block. PMID- 26138535 TI - Living with CML: is death no longer the end (point)? PMID- 26138536 TI - Look into my eyes, please. PMID- 26138537 TI - PACSIN2: a BAR-rier forming the megakaryocyte DMS. PMID- 26138538 TI - FXa variants advance toward a therapy for bleeding. PMID- 26138539 TI - Editorial. In silico ADMET predictions in pharmaceutical research. PMID- 26138540 TI - Artistic occupations are associated with a reduced risk of Parkinson's disease. AB - Parkinson's disease (PD) is preceded by a premotor phase of unknown duration. Dopaminergic degeneration during this phase may lead to subtle cognitive and behavioural changes, such as decreased novelty seeking. Consequently, premotor subjects might be most comfortable in jobs that do not require optimal dopamine levels, leading to an overrepresentation in structured and predictable occupations, or an underrepresentation in artistic occupations. In a case-control study, 750 men with PD (onset >=40 years) and 1300 healthy men completed a validated questionnaire about their lifetime occupational status. Occupations were classified using the RIASEC model. Odds ratios (ORs) were calculated for the conventional and artistic categories, both for the most recent occupation before symptom onset, and for the very first occupation. Because farming has been associated with a PD risk, ORs were calculated separately for farming. A reduced risk of PD was found for men with an artistic occupation late in life (OR 0.14, 95% CI 0.04-0.53), while an artistic first occupation did not prevent PD (OR 0.72, CI 0.32-1.59). Conventional occupations showed no increased risk (recent: OR 1.07, CI 0.70-1.64; first: OR 1.14, CI 0.77-1.71). In support of previous reports, farming was associated with an increased risk of PD (recent: OR 2.6, CI 1.4-4.6; first: OR 2.7, CI 1.6-4.5). PD patients were older than controls, but various statistical corrections for age all lead to similar results. Artistic occupations late in life are associated with a reduced risk of subsequent PD, perhaps because this reflects a better preserved dopaminergic state. No initial occupation predicted PD, suggesting that the premotor phase starts later in life. PMID- 26138541 TI - Relevance of hippocampal integrity for memory outcome after surgical treatment of mesial temporal lobe epilepsy. AB - Surgical treatment of unilateral mesial temporal lobe epilepsy (mTLE) particularly bears the risk of episodic memory decline. The present study investigates the role of the ipsilateral hippocampal integrity for postoperative change in material-specific memory performance. In 104 patients who had undergone epilepsy surgery for unilateral mTLE, we analyzed pre- to postoperative changes of verbal and figural memory as a function of segmental neuronal cell densities of the resected hippocampus (cornu ammonis, CA1-4; internal and external limb of the dentate gyrus, DG). Results were controlled for side of surgery and hemispheric dominance. Surgery caused significant memory decline, especially with regard to verbal memory after left temporal resections. Seizure freedom (65 % Engel Ia) did not affect memory outcome. Higher neuronal cell densities of the resected left hippocampus were associated with greater declines in verbal memory parameters (r = -0.27 to r = -0.39, p < 0.05), especially when excluding patients with atypical hemispheric dominance (r = -0.34 to r = -0.60, p < 0.05; significant correlations across all hippocampal subfields). There were no systematic correlations between neuronal cell densities of the resected right hippocampus and memory changes. The results emphasize the role of the structural and functional integrity of the hippocampus within the left dominant hemisphere for the degree of verbal memory decline after temporal lobe surgery. Presurgical verbal memory performance may be taken as a marker of ipsilateral left hippocampal integrity and may contribute to individual risk-benefit evaluations before epilepsy surgery. Finally, more precise neuropsychological markers of right hippocampal integrity are needed. PMID- 26138542 TI - Dominant and novel clades of Candidatus Accumulibacter phosphatis in 18 globally distributed full-scale wastewater treatment plants. AB - Here we employed quantitative real-time PCR (qPCR) assays for polyphosphate kinase 1 (ppk1) and 16S rRNA genes to assess relative abundances of dominant clades of Candidatus Accumulibacter phosphatis (referred to Accumulibacter) in 18 globally distributed full-scale wastewater treatment plants (WWTPs) from six countries. Accumulibacter were not only detected in the 6 WWTPs performing biological phosphorus removal, but also inhabited in the other 11 WWTPs employing conventional activated sludge (AS) with abundances ranging from 0.02% to 7.0%. Among the AS samples, clades IIC and IID were found to be dominant among the five Accumulibacter clades. The relative abundance of each clade in the Accumulibacter lineage significantly correlated (p < 0.05) with the influent total phosphorus and chemical oxygen demand instead of geographical factors (e.g. latitude), which showed that the local wastewater characteristics and WWTPs configurations could be more significant to determine the proliferation of Accumulibacter clades in full-scale WWTPs rather than the geographical location. Moreover, two novel Accumulibacter clades (IIH and II-I) which had not been previously detected were discovered in two enhanced biological phosphorus removal (EBPR) WWTPs. The results deepened our understanding of the Accumulibacter diversity in environmental samples. PMID- 26138543 TI - Correlation of interleukin-4 levels with Plasmodium falciparum malaria parasitaemia in Sudanese children. AB - OBJECTIVES: This study aimed to measure the level of interleukin-4 (IL-4) in the serum of children patients with falciparum malaria and to correlate the production of this cytokine with the severity of malaria parasitaemia. METHODS: One hundred ten patients with malaria participated in this study (53 males and 57 females) and their results were compared with that of 60 healthy control subjects. Their ages ranged between 6 months and 15 years. For the detection of parasitaemia, a calibrated thick-smear technique was used with standard Giemsa staining. For designation of the relative parasite count, a simple code from one to four crosses is used according to the criteria mentioned by Gilles and Warrell. The blood samples were assessed for IL-4 using enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Thirty-three malaria patients (30.27%) had one cross (+) parasitaemia, 13 patients (11.93%) had (++) parasitaemia, 24 patients (22.02%) had (+++) parasitaemia and 39 patients (35.78%) had (++++) parasitaemia. There was a significant difference (P<0.009) in the concentration of IL-4 between malaria patients (160.74+/-25.5 pg/ml) and control group (62.136+/-18.16 pg/ml). Uncomplicated malaria patients showed the highest record of IL-4 level followed by cerebral malaria (CM) group and then severe malaria anaemia group (SMA) (255.8+/-54.13, 102.7+/-34.88 and 90.95+/ 20.90 pg/ml respectively, P>0.0001). CONCLUSION: It was concluded that elevation of serum IL-4 in Sudanese children suffering from Plasmodium falciparum malaria is correlated with the severity of malaria hyperparasitaemia rather than with the severity of the disease. PMID- 26138545 TI - Neonatal outcome in women with preterm premature rupture of membranes (PPROM) between 18 and 26 weeks. AB - OBJECTIVE: The aim of this study was to identify adverse neonatal outcomes and identifies the predictors of adverse neonatal outcomes in premature rupture of membranes before 26 weeks. METHODS: Data were collected between January 2005 and December 2011 from all pregnant women who presented preterm premature rupture of membranes (PPROM) between 18 and 26 complete weeks of gestation and were admitted to one of three Brazilian institutes. The adverse outcomes included mortality or the development of a severe morbidity during the length of stay in the neonatal intensive care unit (NICU). The descriptive statistics of the population were reported. A multiple logistic regression was performed for each predictor of neonatal adverse outcomes. The area under the receiver operating characteristics curves for the birth weight was calculated. RESULTS: Composite adverse outcomes during the NICU stay occurred in 82.1% (n = 23) of the cases and included 33 (54%) neonatal deaths, 19 (67.8%) cases of retinopathy of prematurity (ROP), 13 (46.4%) cases of pulmonary hypoplasia (BPD), 8 (28.5%) cases of periventricular intraventricular hemorrhage (PIH) and 3 (10.7%) cases of periventricular leukomalacia (PVL). Only 17.8% (n = 5) of the neonates survived without morbidity. The area under the curve for the birth weight was 0.90 (95% IC: 0.81 0.98) for the prediction of mortality. CONCLUSIONS: PPROM before 26 weeks has a high morbidity and mortality, and the significant predictors of neonatal mortality and adverse outcomes were antibiotic prophylaxis, latency period, GA at birth and birth weight. Nevertheless, the only independent significant predictor of survival rate was birth weight. PMID- 26138544 TI - Angelica gigas ameliorate depression-like symptoms in rats following chronic corticosterone injection. AB - BACKGROUND: Repeated injection of corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. We examined the effects of Angelica gigas extract (AGN) treatment in a rat model of depressive and anxiety-like behaviors, induced by chronic CORT exposure. METHODS: Male rats received 10, 20, or 50 mg/kg AGN (i.p.) 30 min prior to a daily injection of CORT for 21 consecutive days. Activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotropin-releasing factor in the hypothalamus. RESULTS: Daily AGN administration significantly reversed the depression and anxiety-like behavioral abnormalities. It also blocked increases in tyrosine hydroxylase expression in the locus coeruleus, and suppressed the decreased expression levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB mRNAs in the hippocampus. CONCLUSIONS: These findings indicate that administration of AGN prior to high-dose exogenous CORT significantly improved helpless behaviors, possibly by modulating the central noradrenergic system and regulation of BDNF expression in rats. Thus, AGN may be a useful agent for the treatment or alleviation of psychiatric disorders associated with depression and anxiety disorders. PMID- 26138546 TI - A Randomized Trial on Health-Related Patient Satisfaction Level with High Efficiency Online Hemodiafiltration versus High-Flux Dialysis. AB - BACKGROUND/AIM: Our aim was to investigate the effect of on-line HDF versus high flux (HF) hemodialysis (HD) on a patient's health-related satisfaction level. METHODS: Overall, 72 patients, on regular low-flux HD for 51 +/- 26 month mean age of 54 +/- 12 years, were randomized to HF (group 1, n = 36) and to HDF (group 2, n = 36) and followed up for 24 months. Assessment was based on the patient's satisfaction level using modified questionnaires of the validated Kidney Disease Quality of Life-Short Form (KDQOL-SF) version 1.3. RESULTS: The HDF group achieved a higher satisfaction level than the HF group (p < 0.0001) with less cramps (3 +/- 5 vs. 55 +/- 8), itching (9 +/- 10 vs. 48 +/- 10), joint pain and stiffness (24 +/- 10 vs. 83 +/- 8), and improvement in general mood (94 +/- 9 vs. 28 +/- 16), sexual performance (57 +/- 10 vs. 5 +/- 5), and social activity (82 +/- 9 vs. 15 +/- 8). CONCLUSION: High-efficiency postdilution on-line HDF versus high-flux HD significantly improved patients' satisfaction and quality of life, including social, physical, and professional activities. PMID- 26138547 TI - Copper-catalyzed cascade azidation-cyclization of tryptophols and tryptamines. AB - The copper-catalyzed cascade azidation-cyclization of tryptophols and tryptamines has been developed. This cascade reaction uses readily available and cheap sodium azide as a nitrogen source to gave 3-azido furoindolines and pyrrolidinoindolines under mild reaction conditions. PMID- 26138548 TI - Enhanced leaf photosynthesis as a target to increase grain yield: insights from transgenic rice lines with variable Rieske FeS protein content in the cytochrome b6 /f complex. AB - Although photosynthesis is the most important source for biomass and grain yield, a lack of correlation between photosynthesis and plant yield among different genotypes of various crop species has been frequently observed. Such observations contribute to the ongoing debate whether enhancing leaf photosynthesis can improve yield potential. Here, transgenic rice plants that contain variable amounts of the Rieske FeS protein in the cytochrome (cyt) b6 /f complex between 10 and 100% of wild-type levels have been used to investigate the effect of reductions of these proteins on photosynthesis, plant growth and yield. Reductions of the cyt b6 /f complex did not affect the electron transport rates through photosystem I but decreased electron transport rates through photosystem II, leading to concomitant decreases in CO2 assimilation rates. There was a strong control of plant growth and grain yield by the rate of leaf photosynthesis, leading to the conclusion that enhancing photosynthesis at the single-leaf level would be a useful target for improving crop productivity and yield both via conventional breeding and biotechnology. The data here also suggest that changing photosynthetic electron transport rates via manipulation of the cyt b6 /f complex could be a potential target for enhancing photosynthetic capacity in higher plants. PMID- 26138549 TI - The clinical effectiveness and cost-effectiveness of point-of-care tests (CoaguChek system, INRatio2 PT/INR monitor and ProTime Microcoagulation system) for the self-monitoring of the coagulation status of people receiving long-term vitamin K antagonist therapy, compared with standard UK practice: systematic review and economic evaluation. AB - BACKGROUND: Self-monitoring (self-testing and self-management) could be a valid option for oral anticoagulation therapy monitoring in the NHS, but current evidence on its clinical effectiveness or cost-effectiveness is limited. OBJECTIVES: We investigated the clinical effectiveness and cost-effectiveness of point-of-care coagulometers for the self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy, compared with standard clinic monitoring. DATA SOURCES: We searched major electronic databases (e.g. MEDLINE, MEDLINE In Process & Other Non-Indexed Citations, EMBASE, Bioscience Information Service, Science Citation Index and Cochrane Central Register of Controlled Trials) from 2007 to May 2013. Reports published before 2007 were identified from the existing Cochrane review (major databases searched from inception to 2007). The economic model parameters were derived from the clinical effectiveness review, other relevant reviews, routine sources of cost data and clinical experts' advice. REVIEW METHODS: We assessed randomised controlled trials (RCTs) evaluating self-monitoring in people with atrial fibrillation or heart valve disease requiring long-term anticoagulation therapy. CoaguChek((r)) XS and S models (Roche Diagnostics, Basel, Switzerland), INRatio2((r)) PT/INR monitor (Alere Inc., San Diego, CA USA), and ProTime Microcoagulation system((r)) (International Technidyne Corporation, Nexus Dx, Edison, NJ, USA) coagulometers were compared with standard monitoring. Where possible, we combined data from included trials using standard inverse variance methods. Risk of bias assessment was performed using the Cochrane risk of bias tool. A de novo economic model was developed to assess the cost-effectiveness over a 10-year period. RESULTS: We identified 26 RCTs (published in 45 papers) with a total of 8763 participants. CoaguChek was used in 85% of the trials. Primary analyses were based on data from 21 out of 26 trials. Only four trials were at low risk of bias. Major clinical events: self-monitoring was significantly better than standard monitoring in preventing thromboembolic events [relative risk (RR) 0.58, 95% confidence interval (CI) 0.40 to 0.84; p = 0.004]. In people with artificial heart valves (AHVs), self-monitoring almost halved the risk of thromboembolic events (RR 0.56, 95% CI 0.38 to 0.82; p = 0.003) and all-cause mortality (RR 0.54, 95% CI 0.32 to 0.92; p = 0.02). There was greater reduction in thromboembolic events and all cause mortality through self-management but not through self-testing. Intermediate outcomes: self-testing, but not self-management, showed a modest but significantly higher percentage of time in therapeutic range, compared with standard care (weighted mean difference 4.44, 95% CI 1.71 to 7.18; p = 0.02). Patient-reported outcomes: improvements in patients' quality of life related to self-monitoring were observed in six out of nine trials. High preference rates were reported for self-monitoring (77% to 98% in four trials). Net health and social care costs over 10 years were L7295 (self-monitoring with INRatio2); L7324 (standard care monitoring); L7333 (self-monitoring with CoaguChek XS) and L8609 (self-monitoring with ProTime). The estimated quality-adjusted life-year (QALY) gain associated with self-monitoring was 0.03. Self-monitoring with INRatio2 or CoaguChek XS was found to have ~ 80% chance of being cost-effective, compared with standard monitoring at a willingness-to-pay threshold of L20,000 per QALY gained. CONCLUSIONS: Compared with standard monitoring, self-monitoring appears to be safe and effective, especially for people with AHVs. Self-monitoring, and in particular self-management, of anticoagulation status appeared cost-effective when pooled estimates of clinical effectiveness were applied. However, if self monitoring does not result in significant reductions in thromboembolic events, it is unlikely to be cost-effective, based on a comparison of annual monitoring costs alone. Trials investigating the longer-term outcomes of self-management are needed, as well as direct comparisons of the various point-of-care coagulometers. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013004944. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26138550 TI - Synthetic Polymer Hybridization with DNA and RNA Directs Nanoparticle Loading, Silencing Delivery, and Aptamer Function. AB - We report herein discrete triplex hybridization of DNA and RNA with polyacrylates. Length-monodisperse triazine-derivatized polymers were prepared on gram-scale by reversible addition-fragmentation chain-transfer polymerization. Despite stereoregio backbone heterogeneity, the triazine polymers bind T/U-rich DNA or RNA with nanomolar affinity upon mixing in a 1:1 ratio, as judged by thermal melts, circular dichroism, gel-shift assays, and fluorescence quenching. We call these polyacrylates "bifacial polymer nucleic acids" (bPoNAs). Nucleic acid hybridization with bPoNA enables DNA loading onto polymer nanoparticles, siRNA silencing delivery, and can further serve as an allosteric trigger of RNA aptamer function. Thus, bPoNAs can serve as tools for both non-covalent bioconjugation and structure-function nucleation. It is anticipated that bPoNAs will have utility in both bio- and nanotechnology. PMID- 26138551 TI - Direct high-throughput amplification and sequencing of immunoglobulin genes from single human B cells. PMID- 26138552 TI - Effect of Ki-67 on Immunohistochemical Classification of Luminal A to Luminal B Subtypes of Breast Carcinoma. AB - It has recently been proposed to include an immunohistochemical marker of cell proliferation, Ki-67, as an element with which to classify the molecular subtypes of breast cancer. The objective of this study was to evaluate the effect of the introduction of the Ki-67 marker on the molecular classification of breast cancer by immunohistochemistry. This study was performed on 234 cases of invasive ductal carcinoma of the breast submitted to two immunohistochemical classification panels, one including Ki-67 and the other not. The data obtained with the two classifications were correlated with well-established prognostic factors such as histologic grade, the number of lymph nodes affected and tumor size. The molecular classification without Ki-67 identified: 136 cases of luminal A (58.1%), 19 cases of luminal B (8.1%), 27 cases of human epidermal growth-factor receptor 2 overexpressing (11.5%), 27 cases of basal-like (11.5%), and 25 cases of nonbasal-like triple-negative tumors (10.7%). When Ki-67 was included, this situation changed significantly, with the following cases being identified: 72 cases of luminal A (30.8%) and 83 cases of luminal B tumors (35.5%), resulting in a Kappa score of 0.216. Evaluation of correlations between the luminal A and luminal B tumor subtypes and the selected prognostic factors showed a statistically significant difference only when Ki-67 was included and only with respect to histologic grade (p < 0.001). The new classification with Ki-67 significantly altered the prevalence of the luminal A and luminal B subtypes and improved correlation with the histologic grade. PMID- 26138553 TI - Selective C1 Lesioning Slightly Decreases Angiotensin II Type I Receptor Expression in the Rat Rostral Ventrolateral Medulla (RVLM). AB - Cardiovascular homeostasis is regulated in large part by the rostral ventrolateral medulla (RVLM) in mammals. Projections from the RVLM to the intermediolateral column of the thoracolumbar spinal cord innervate preganglionic neurons of the sympathetic nervous system causing elevation of blood pressure and heart rate. A large proportion, but not all, of the neurons in the RVLM contain the enzymes necessary for the production of epinephrine and are identified as the C1 cell group. Angiotensin II (Ang II) activates the RVLM acting upon AT1 receptors. To assess the proportion of AT1 receptors that are located on C1 neurons in the rat RVLM this study employed an antibody to dopamine-beta hydroxylase conjugated to saporin, to selectively destroy C1 neurons in the RVLM. Expression of tyrosine hydroxylase immunoreactive neurons in the RVLM was reduced by 57 % in the toxin injected RVLM compared to the contralateral RVLM. In contrast, densitometric analysis of autoradiographic images of (125)I sarcosine(1), isoleucine(8) Ang II binding to AT1 receptors of the injected side RVLM revealed a small (10 %) reduction in AT1-receptor expression compared to the contralateral RVLM. These results suggest that the majority of AT1 receptors in the rat RVLM are located on non-C1 neurons or glia. PMID- 26138554 TI - Fluctuations in Cytosolic Calcium Regulate the Neuronal Malate-Aspartate NADH Shuttle: Implications for Neuronal Energy Metabolism. AB - The malate-aspartate NADH shuttle (MAS) operates in neurons and other cells to translocate reducing equivalents from the cytosol to the mitochondrial matrix, thus allowing a continued flux through the glycolytic pathway and metabolism of extracellular lactate. Recent discoveries have taught us that MAS is regulated by fluctuations in cytosolic Ca(2+) levels, and that this regulation is required to maintain a tight coupling between neuronal activity and mitochondrial respiration and oxidative phosphorylation. At cytosolic Ca(2+) fluctuations below the threshold of the mitochondrial calcium uniporter, there is a positive correlation between Ca(2+) and MAS activity; however, if cytosolic Ca(2+) increases above the threshold, MAS activity is thought to be reduced by an intricate mechanism. The latter forces the neurons to partly rely on anaerobic glycolysis producing lactate that may be metabolized subsequently, by neurons or other cells. In this review, we will discuss the evidence for Ca(2+)-mediated regulation of MAS that have been uncovered over the last decade or so, together with the need for further verification, and examine the metabolic ramifications for neurons. PMID- 26138555 TI - Quorum sensing inhibitors from Leucetta chagosensis Dendy, 1863. AB - Sponges are a rich source for investigation of bioactive small molecules. They have been mostly investigated for the search of new pharmacological models or therapeutic agents for the treatment of human diseases. Micro-organisms can also represent a virulent pathogen for marine invertebrates such as sponges, which need to protect themselves against these microbes. Sponges' self defence mechanisms involving dialogue molecules thus represent a pertinent research track for potent anti-infective and anti-biofilm activities such as quorum sensing inhibitors (QSIs). The investigation of the QSI crude extract of Leucetta chagosensis Dendy, 1863 led to the isolation of three new alkaloids, isonaamine D, di-isonaamidine A and leucettamine D, along with the known isonaamine A and isonaamidine A. Isonaamidine A and isonaamine D were identified as inhibitors of the three quorum sensing pathways of Vibrio harveyi (CAI-1, AI-2 and harveyi auto inducer), but isonaamidine A displayed the strongest activity on AI-2 biosensor. Both compounds are new examples of natural QSIs of V. harveyi. These results outline the importance of these secondary metabolites for their producing organisms themselves in their natural environment, as well as the potential of the marine resource for aquaculture needs. SIGNIFICANCE AND IMPACT OF THE STUDY: A new type of quorum sensing inhibitors was isolated from the sponge Leucetta chagosensis. One of them inhibits strongly the AI-2 channel of Vibrio harveyi, a marine pathogen of special importance in aquaculture. The activity of five different related compounds, including three new natural products discovered there, was investigated leading to structure-activity relationships which are useful for the design of new quorum sensing inhibitors to control marine infectious pathogens. PMID- 26138556 TI - A facile and regioselective synthesis of 1-tetralones via silver-catalyzed ring expansion. AB - A regioselective synthesis of 1-tetralones via silver-catalyzed ring expansion is described. A variety of 1-tetralones are furnished under mild reaction conditions from tertiary cyclobutanols regardless of the electronic properties and steric hindrance of substituents, providing a new and practical method to access diverse 1-tetralone building blocks. Preliminary experimental and DFT studies revealed that a radical-mediated sequence of C-C bond cleavage/C-C bond formation is involved. PMID- 26138557 TI - Inability of rat DPP4 to allow MERS-CoV infection revealed by using a VSV pseudotype bearing truncated MERS-CoV spike protein. AB - Middle East respiratory syndrome (MERS) coronavirus (Co-V) contains a single spike (S) protein, which binds to a receptor molecule, dipeptidyl peptidase 4 (DPP4; also known as CD26), and serves as a neutralizing antigen. Pseudotyped viruses are useful for measuring neutralization titers against highly infectious viruses as well as for studying their mechanism of entry. In this study, we constructed a series of cytoplasmic deletion mutants of MERS-CoV S and compared the efficiency with which they formed pseudotypes with vesicular stomatitis virus. A pseudotype bearing an S protein with the C-terminal 16 amino acids deleted (MERSpv-St16) reached a maximum titer that was approximately tenfold higher than that of a pseudotype bearing a non-truncated full-length S protein. Using MERSpv-St16, we demonstrated the inability of rat DPP4 to serve as a functional receptor for MERS-CoV, suggesting that rats are not susceptible to MERS-CoV infection. This study provides novel information that enhances our understanding of the host range of MERS-CoV. PMID- 26138558 TI - Complete genome sequence of a novel dsRNA mycovirus isolated from the phytopathogenic fungus Fusarium oxysporum f. sp. dianthi. AB - A novel double-stranded RNA (dsRNA) mycovirus, designated Fusarium oxysporum f. sp. dianthi mycovirus 1 (FodV1), was isolated from a strain of the phytopathogenic fungus F. oxysporum f. sp. dianthi. The FodV1 genome had four dsRNA segments, designated, from the largest to the smallest one, dsRNA 1, 2 3, and 4. Each one of these segments contained a single open reading frame (ORF). dsRNA 1 (3555 bp) and dsRNA 3 (2794 bp) encoded a putative RNA-dependent RNA polymerase (RdRp) and a putative coat protein (CP), respectively. dsRNA 2 (2809 bp) and dsRNA 4 (2646 bp) contained ORFs encoding hypothetical proteins (named P2 and P4, respectively) with unknown functions. Analysis of its genomic structure, homology searches of the deduced amino acid sequences, and phylogenetic analysis all indicated that FodV1 is a new member of the family Chrysoviridae. This is the first report of the complete genomic characterization of a mycovirus identified in the plant pathogen Fusarium oxysporum. PMID- 26138559 TI - Emerging infectious disease or evidence of endemicity? A multi-season study of beak and feather disease virus in wild red-crowned parakeets (Cyanoramphus novaezelandiae). AB - Beak and feather disease virus (BFDV) is a single-stranded DNA virus that is the etiological agent of beak and feather disease in both wild and captive parrots. Given that BFDV is globally recognized as a conservation threat for wild parrots, between 2011-2013, red-crowned parakeets (Cyanoramphus novaezelandiae, n = 229), which are endemic to New Zealand, were captured in mist nets on Tiritiri Matangi Island and Hauturu-o-Toi/Little Barrier Island (LBI), New Zealand, for disease surveillance. Blood and feathers from all birds were tested by PCR for BFDV, and full genomes were recovered and sequenced. A subset of blood samples (n = 96) were tested for antibodies to BFDV by the haemagglutination inhibition (HI) test. A further 238 feather samples were obtained from red-crowned parakeets from three sites in the Wellington region of the North Island, and these were screened for BFDV. The DNA-based prevalence of BFDV infection determined on Tiritiri Matangi Island was 1.09% (CI 95 %, 0.1-3.9%); on Hauturu-o-Toi/LBI, 4.4% (95% CI, 0.5% 15.1%); on Kapiti Island, 3.4% (CI 95%, 1.1-7.8%); at the ZEALANDIA-Karori sanctuary, 1.6% (95% CI, 0-8.4%); and on Matiu-Somes Island, 0% (CI 95%, 0 12.3%). Seroprevalence for BFDV, indicating prior or current exposure, in the Tiritiri Matangi Island population, it was 2% (CI 95%, 0-10.1%), and in the Hauturu-o-Toi/LBI population was 14% (CI 95%, 5.3-27.9%). BFDV-positive birds showed no signs of clinical disease, with the exception of an individual bird obtained opportunistically from Shakespear Regional Park during the study period, which had classical signs of feather loss. Phylogenetic analysis of the 11 full genome sequences recovered from BFDV-positive red-crowned parakeets revealed evidence of ongoing viral flow between red-crowned parakeets and eastern rosellas (Platycercus eximius) in the Hauraki Gulf/Auckland region, with separate but closely related strains from the Wellington region of the North Island. This is the first study to report HI results for a New Zealand endemic parrot species, and the first epidemiological analysis of serial cross-sectional surveys in a BFDV-infected population of red-crowned parakeets in New Zealand. We postulate that although BFDV remains a threat to small, isolated or naive populations of parrots globally, the low viral prevalence in this and other studies suggests that native parakeets in New Zealand may act as dead-end or spillover hosts. PMID- 26138560 TI - Changing trends in carrier screening for genetic disease in the United States. AB - Genetic disease is the leading cause of infant death in the United States, accounting for approximately 20% of annual infant mortality. Advances in genomic medicine and technological platforms have made possible low cost, pan-ethnic expanded genetic screening that enables obstetric care providers to offer screening for over 100 recessive genetic diseases. However, the rapid integration of genomic medicine into routine obstetric practice has raised some concerns about the practical implementation of such testing. These changing trends in carrier screening, along with concerns and potential solutions, will be addressed. PMID- 26138561 TI - Subfoveal Choroidal Thickness Is Associated with Blood Hematocrit Level. AB - PURPOSE: To compare subfoveal choroidal thickness (SFCT), retinal vessel caliber, and ocular pulse amplitude between treated polycythemia vera (PV) patients and healthy adults. METHODS: Forty patients with PV and 40 age- and sex-matched healthy controls were recruited for this cross-sectional study. Spectral-domain optical coherence tomography was used for SFCT and retinal vessel caliber measurements. The Pascal dynamic contour tonometer was used for ocular pulse amplitude measurements. The correlations of blood hematocrit levels with the studied ocular parameters were analyzed. RESULTS: There were no statistically significant differences between the PV patients and controls in SFCT, retinal vessel caliber, and ocular pulse amplitude (p > 0.05). SFCT was associated with hematocrit level in both PV patients and healthy adults (p < 0.05). CONCLUSIONS: Although SFCT, retinal vessel caliber, and ocular pulse amplitude parameters are similar in treated PV patients and healthy controls, SFCT is associated with hematocrit level. PMID- 26138562 TI - Dual silencing of Bcl-2 and Survivin by HSV-1 vector shows better antitumor efficacy in higher PKR phosphorylation tumor cells in vitro and in vivo. AB - RNA interference (RNAi) is a promising tool for cancer therapy, but its delivery strategy is a major challenge for its application. Oncolytic herpes simplex virus type 1 (HSV-1) is not only an effective antitumor drug but also an excellent vector. Herein, RNAi of oncogenes Bcl-2 and Survivin was combined with oncolytic HSV-1 (ICP34.5-/ICP6-/ICP47-/CMV-GM-CSF) and a new vector HSV010-BS was constructed. Transfected cell viability assays and animal experiments revealed that the dual silencing of Bcl-2 and Survivin improved the antitumor effect of oncolytic HSV-1 in vitro and in vivo, while the antitumor effect was correlated with the phosphorylation levels of PKR of the tumor cells. The higher the phosphorylation levels of PKR of the tumor cells, the weaker the replication ability of oncolytic HSV-1, and the more powerful HSV010-BS was than its control vectors in inhibiting the growth of the tumor cells. The results provided direct supportive proofs for a new potential cancer therapy strategy. PMID- 26138563 TI - Percutaneous minimally invasive fetoscopic surgery for spina bifida aperta. Part III: neurosurgical intervention in the first postnatal year. AB - OBJECTIVE: To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA). METHODS: This was a retrospective analysis of a cohort of 71 fetuses which underwent minimally invasive fetoscopic patch coverage of SBA between 21 + 0 and 29 + 1 weeks of gestation. Postnatal neurosurgical procedures were classified into two types: re coverage of the SBA within the first 3 months following birth, and shunt placement as treatment of associated hydrocephalus within the first year. RESULTS: Location of the SBA was lumbosacral in 59 cases, lumbar in seven, thoracic in three and sacral in two. In total, 20/71 (28%) patients underwent early postnatal neurosurgical intervention by means of re-coverage of the SBA. This was performed because of cerebrospinal fluid leakage in seven (35%), adhesions with functional deterioration in three (15%), incomplete coverage in five (25%) and skin defect in five (25%) cases. Ventriculoperitoneal shunt placement within 1 year was required in 32 (45%) cases and was preceded by ventriculostomy in two. Three (4%) infants needed Chiari decompression surgery in the first 12 months following birth, because of syringomyelia or gait disturbance. CONCLUSIONS: Fetoscopic patch coverage of SBA may require postnatal re-coverage in some cases. In most cases, conservative wound treatment shows good results, without requiring neurosurgical intervention. The low 1-year-shunt rate is comparable to data of the Management of Myelomeningocele Study and lower compared with published data of patients with postnatal only coverage of SBA. PMID- 26138564 TI - Detection of methicillin-resistant Staphylococcus pseudintermedius ST169 and novel ST354 SCCmec II-III isolates related to the worldwide ST71 clone. AB - The recent appearance of methicillin-resistant Staphylococcus pseudintermedius (MRSP) is a concern for both veterinary and human healthcare. MRSP clonal lineages with sequence type (ST) 71-spa t02-staphylococcal cassette chromosome mec (SCCmec) II-III and ST68-spa t06-SCCmec V have spread throughout Europe and North America, respectively. The current study compared the molecular characteristics of 43 MRSP isolates from dogs in Japan with those of MRSP from previous reports using multilocus sequence typing based on seven housekeeping genes, SCCmec typing, and detection of antimicrobial resistance genes. Three related clonal lineages, ST71, ST169, and the newly registered ST354, were observed in SCCmec II-III isolates from Japan, despite MRSP SCCmec II-III isolates being thought to belong to a single clonal lineage. The majority of SCCmec II-III isolates belonging to ST169 (9/11) and ST354 (3/3), but not ST71 (0/11), harboured tetM. Four STs were observed for the SCCmec V isolates; however, neither ST68 nor related STs were found in the Japanese MRSP isolates. In conclusion, MRSP SCCmec II-III isolates from Japan belonged to ST71 and related STs (ST169 and ST354). A variety of MRSP SCCmec V clones, including some novel clones, were identified. PMID- 26138566 TI - Design and Development of ChemInfoCloud: An Integrated Cloud Enabled Platform for Virtual Screening. AB - The power of cloud computing and distributed computing has been harnessed to handle vast and heterogeneous data required to be processed in any virtual screening protocol. A cloud computing platorm ChemInfoCloud was built and integrated with several chemoinformatics and bioinformatics tools. The robust engine performs the core chemoinformatics tasks of lead generation, lead optimisation and property prediction in a fast and efficient manner. It has also been provided with some of the bioinformatics functionalities including sequence alignment, active site pose prediction and protein ligand docking. Text mining, NMR chemical shift (1H, 13C) prediction and reaction fingerprint generation modules for efficient lead discovery are also implemented in this platform. We have developed an integrated problem solving cloud environment for virtual screening studies that also provides workflow management, better usability and interaction with end users using container based virtualization, OpenVz. PMID- 26138565 TI - Discovery of Natural Product-Derived 5-HT1A Receptor Binders by Cheminfomatics Modeling of Known Binders, High Throughput Screening and Experimental Validation. AB - The human 5-hydroxytryptamine receptor subtype 1A (5-HT1A) is highly expressed in the raphe nuclei region and limbic structures; for that reason 5-HT1A has served as a promising target for treating human mood disorders and neurodegenerative diseases. We have developed binary quantitative structure-activity relationship (QSAR) models for 5- HT1A binding using data retrieved from the WOMBAT database and the k-Nearest Neighbor (kNN) machine learning method. A rigorous QSAR modeling and screening workflow had been followed, with extensive internal and external validation processes. The models' classification accuracies to discriminate 5-HT1A binders from the non-binders are as high as 96% for the external validation. These models were employed further to mine two major natural products screening libraries, i.e. TimTec Natural Product Library (NPL) and Natural Derivatives Library (NDL). In the end five screening hits were tested by radioligand binding assays with a success rate of 40%, and two Library compounds were confirmed to be binders at the MUM concentration against the human 5-HT1A receptor. The combined application of rigorous QSAR modeling and model-based virtual screening presents a powerful means for profiling natural products compounds with important biomedical activities. PMID- 26138567 TI - MegaMiner: A Tool for Lead Identification Through Text Mining Using Chemoinformatics Tools and Cloud Computing Environment. AB - Virtual screening is an indispensable tool to cope with the massive amount of data being tossed by the high throughput omics technologies. With the objective of enhancing the automation capability of virtual screening process a robust portal termed MegaMiner has been built using the cloud computing platform wherein the user submits a text query and directly accesses the proposed lead molecules along with their drug-like, lead-like and docking scores. Textual chemical structural data representation is fraught with ambiguity in the absence of a global identifier. We have used a combination of statistical models, chemical dictionary and regular expression for building a disease specific dictionary. To demonstrate the effectiveness of this approach, a case study on malaria has been carried out in the present work. MegaMiner offered superior results compared to other text mining search engines, as established by F score analysis. A single query term 'malaria' in the portlet led to retrieval of related PubMed records, protein classes, drug classes and 8000 scaffolds which were internally processed and filtered to suggest new molecules as potential anti-malarials. The results obtained were validated by docking the virtual molecules into relevant protein targets. It is hoped that MegaMiner will serve as an indispensable tool for not only identifying hidden relationships between various biological and chemical entities but also for building better corpus and ontologies. PMID- 26138568 TI - Prediction of Bioactive Compounds Using Computed NMR Chemical Shifts. AB - NMR based chemical shifts are an important diagnostic parameter for structure elucidation as they capture rich information related to conformational, electronic and stereochemical arrangement of functional groups in a molecule which is responsible for its activity towards any biological target. The present work discusses the importance of computing NMR chemical shifts from molecular structures. The NMR chemical shift data (experimental or computed) was used to generate fingerprints in binary formats for mapping molecular fragments (as descriptors) and correlating with the bioactivity classes. For this study, chemical shift data derived binary fingerprints were computed for 149 classes and 4800 bioactive molecules. The sensitivity and selectivity of fingerprints in discriminating molecules belonging to different therapeutic categories was assessed using a LibSVM based classifier. An accuracy of 82% for proton and 94% for carbon NMR fingerprints were obtained for anti-psoriatic and anti-psychotic molecules demonstrating the effectiveness of this approach for virtual screening. PMID- 26138569 TI - Role of Chemical Reactivity and Transition State Modeling for Virtual Screening. AB - Every drug discovery research program involves synthesis of a novel and potential drug molecule utilizing atom efficient, economical and environment friendly synthetic strategies. The current work focuses on the role of the reactivity based fingerprints of compounds as filters for virtual screening using a tool ChemScore. A reactant-like (RLS) and a product- like (PLS) score can be predicted for a given compound using the binary fingerprints derived from the numerous known organic reactions which capture the molecule-molecule interactions in the form of addition, substitution, rearrangement, elimination and isomerization reactions. The reaction fingerprints were applied to large databases in biology and chemistry, namely ChEMBL, KEGG, HMDB, DSSTox, and the Drug Bank database. A large network of 1113 synthetic reactions was constructed to visualize and ascertain the reactant product mappings in the chemical reaction space. The cumulative reaction fingerprints were computed for 4000 molecules belonging to 29 therapeutic classes of compounds, and these were found capable of discriminating between the cognition disorder related and anti-allergy compounds with reasonable accuracy of 75% and AUC 0.8. In this study, the transition state based fingerprints were also developed and used effectively for virtual screening in drug related databases. The methodology presented here provides an efficient handle for the rapid scoring of molecular libraries for virtual screening. PMID- 26138570 TI - Chemoinformatics Approach for Building Molecular Networks from Marine Organisms. AB - Natural products obtained from marine sources are considered to be a rich and diverse source of potential drugs. In the present work we demonstrate the use of chemoinformatics approach for the design of new molecules inspired by molecules from marine organisms. Accordingly we have assimilated information from two major scientific domains namely chemoinformatics and biodiversity informatics to develop an interactive marine database named MIMMO (Medicinally Important Molecules from Marine Organisms). The database can be queried for species, molecules, scaffolds, drugs, diseases and associated cumulative biological activity spectrum along with links to the literature resources. Molecular informatics analysis of the molecules obtained from MIMMO was performed to study their chemical space. The distinct skeletal features of the biologically active compounds isolated from marine species were identified. Scaffold molecules and species networks were created to identify common scaffolds from marine source and drug space. An analysis of the entire molecular data revealed a unique list of around 2000 molecules from which ten most frequently occurring distinct scaffolds were obtained. PMID- 26138571 TI - Pharmacophore and Docking Based Virtual Screening of Validated Mycobacterium tuberculosis Targets. AB - Target based virtual screening has surpassed ligand based virtual screening methods in the recent past mainly as it provides more clues regarding intermolecular interactions and takes into consideration the flexible receptor as well. The current methodology describes a computational strategy of predicting Mycobacterium tuberculosis (M. tuberculosis) binders for five well studied targets representing M. tuberculosis proteome encompassing most of the known mechanisms of action. The diversity of the targets was affirmed by their active site analysis and structural studies. The current approach employed pharmacophore searching, docking and clustering techniques in tandem and was validated by enrichment studies using the available Schrodinger data set consisting of 1000 decoys. The application of this methodology was demonstrated by predicting potential molecular targets for fifty newly synthesized compounds. Cross docking studies on the targets were carried out with 4512 known inhibitors utilizing a high performance computing platform to reveal underlying affinity and promiscuity patterns. Optimum binding energy range for all targets as determined by high throughput docking was found to be -3 to -13 kcal/mol. PMID- 26138572 TI - Protein Ligand Complex Guided Approach for Virtual Screening. AB - The target ligand association data is a rich source of information which is not exploited enough for drug design efforts in virtual screening. A java based open source toolkit for Protein Ligand Network Extraction (J-ProLiNE) focused on protein-ligand complex analysis with several features integrated in a distributed computing network has been developed. Sequence alignment and similarity search components have been automated to yield local, global alignment scores along with similarity and distance scores. 10000 proteins with co-crystallized ligands from pdb and MOAD databases were extracted and analyzed for revealing relationships between targets, ligands and scaffolds. Through this analysis, we could generate a protein ligand network to identify the promiscuous and selective scaffolds for multiple classes of proteins targets. Using J-ProLiNE we created a 507 x 507 matrix of protein targets and native ligands belonging to six enzyme classes and analyzed the results to elucidate the protein-protein, protein-ligand and ligand ligand interactions. In yet another application of the J-ProLiNE software, we were able to process kinase related information stored in US patents to construct disease-gene-ligand-scaffold networks. It is hoped that the studies presented here will enable target ligand knowledge based virtual screening for inhibitor design. PMID- 26138573 TI - A Study of Applications of Machine Learning Based Classification Methods for Virtual Screening of Lead Molecules. AB - The ligand-based virtual screening of combinatorial libraries employs a number of statistical modeling and machine learning methods. A comprehensive analysis of the application of these methods for the diversity oriented virtual screening of biological targets/drug classes is presented here. A number of classification models have been built using three types of inputs namely structure based descriptors, molecular fingerprints and therapeutic category for performing virtual screening. The activity and affinity descriptors of a set of inhibitors of four target classes DHFR, COX, LOX and NMDA have been utilized to train a total of six classifiers viz. Artificial Neural Network (ANN), k nearest neighbor (k-NN), Support Vector Machine (SVM), Naive Bayes (NB), Decision Tree--(DT) and Random Forest--(RF). Among these classifiers, the ANN was found as the best classifier with an AUC of 0.9 irrespective of the target. New molecular fingerprints based on pharmacophore, toxicophore and chemophore (PTC), were used to build the ANN models for each dataset. A good accuracy of 87.27% was obtained using 296 chemophoric binary fingerprints for the COX-LOX inhibitors compared to pharmacophoric (67.82%) and toxicophoric (70.64%). The methodology was validated on the classical Ames mutagenecity dataset of 4337 molecules. To evaluate it further, selectivity and promiscuity of molecules from five drug classes viz. anti-anginal, anti-convulsant, anti-depressant, anti-arrhythmic and anti-diabetic were studied. The TPC fingerprints computed for each category were able to capture the drug-class specific features using the k-NN classifier. These models can be useful for selecting optimal molecules for drug design. PMID- 26138574 TI - ChemScreener: A Distributed Computing Tool for Scaffold based Virtual Screening. AB - In this work we present ChemScreener, a Java-based application to perform virtual library generation combined with virtual screening in a platform-independent distributed computing environment. ChemScreener comprises a scaffold identifier, a distinct scaffold extractor, an interactive virtual library generator as well as a virtual screening module for subsequently selecting putative bioactive molecules. The virtual libraries are annotated with chemophore-, pharmacophore- and toxicophore-based information for compound prioritization. The hits selected can then be further processed using QSAR, docking and other in silico approaches which can all be interfaced within the ChemScreener framework. As a sample application, in this work scaffold selectivity, diversity, connectivity and promiscuity towards six important therapeutic classes have been studied. In order to illustrate the computational power of the application, 55 scaffolds extracted from 161 anti-psychotic compounds were enumerated to produce a virtual library comprising 118 million compounds (17 GB) and annotated with chemophore, pharmacophore and toxicophore based features in a single step which would be non trivial to perform with many standard software tools today on libraries of this size. PMID- 26138575 TI - Role of Open Source Tools and Resources in Virtual Screening for Drug Discovery. AB - Advancement in chemoinformatics research in parallel with availability of high performance computing platform has made handling of large scale multi-dimensional scientific data for high throughput drug discovery easier. In this study we have explored publicly available molecular databases with the help of open-source based integrated in-house molecular informatics tools for virtual screening. The virtual screening literature for past decade has been extensively investigated and thoroughly analyzed to reveal interesting patterns with respect to the drug, target, scaffold and disease space. The review also focuses on the integrated chemoinformatics tools that are capable of harvesting chemical data from textual literature information and transform them into truly computable chemical structures, identification of unique fragments and scaffolds from a class of compounds, automatic generation of focused virtual libraries, computation of molecular descriptors for structure-activity relationship studies, application of conventional filters used in lead discovery along with in-house developed exhaustive PTC (Pharmacophore, Toxicophores and Chemophores) filters and machine learning tools for the design of potential disease specific inhibitors. A case study on kinase inhibitors is provided as an example. PMID- 26138576 TI - Consanguinity as an Adjunct Diagnostic Tool. AB - History of consanguinity is important in monogenic disorders as it supports autosomal recessive mode of inheritance. This case report illustrates the use of homozygosity mapping using single nucleotide polymorphism (SNP) microarray data to identify the causative gene in a case with Warburg Micro syndrome (WARBM). This syndrome has non-specific features like microcephaly and cataract; etiological diagnosis based on clinical features is not possible. Four causative genes are known for WARBM syndrome. In such a situation of autosomal recessive disorders of heterogeneous etiologies, SNP microarray and homozygosity mapping is a useful and cost effective strategy. PMID- 26138577 TI - The Tools of the Trade - Physiological Measurements of the Lungs. AB - Pulmonary function assessment plays an integral part in the clinical management of school-aged children with respiratory disease. Pulmonary function tests (PFTs) are being increasingly applied in infants and preschool children too, albeit only in specialised centres. PFTs, when performed and interpreted accurately, provide objective outcome measures which can be used clinically to guide management, for prognostic purposes and in epidemiological research studies. They can be used to determine the nature and severity of lung disease, to ascertain response to treatment and to monitor disease progression. PFTs are rarely diagnostic in their own right with the exception of asthma, but are valuable adjuncts and before clinicians select a PFT they must know what the results are likely to be in the disease being considered. Spirometry and tests of airway calibre and function are the most widely used PFTs, as diseases in children commonly affect airway function. As such, spirometry should be a standard part of the assessment of school-age children who present to the pediatrician with chronic respiratory symptoms. This review will provide a bird's eye view of currently available PFTs in children to assist in the diagnosis and management of respiratory disorders. PMID- 26138578 TI - Evaluation of Acquired Valvular Heart Disease by the Pediatrician: When to Follow, When to Refer for Intervention? Part II. AB - Lesions of the heart valves are the commonest acquired cardiac abnormalities seen in pediatric age group. Aortic regurgitation (AR) results from abnormality of the valve leaflets or of the aortic root. Mitral valve lesion may be associated in patients with rheumatic heart disease (RHD). Left ventricle dilates and may develop dysfunction in advanced states. Coronary perfusion also tends to suffer in severe AR. The symptoms develop later and include dyspnea and palpitations. An early diastolic, high pitched murmur, best heard at base of the heart is the hallmark of AR. All symptomatic patients with severe AR and those with left ventricular dysfunction should undergo surgical intervention. Aortic stenosis (AS) is often due to congenitally bicuspid or unicuspid valve. RHD rarely results in AS; associated AR is common in such cases. The most common cause of tricuspid valve involvement is secondary to dilatation of right ventricle and tricuspid annulus resulting in tricuspid regurgitation (TR). Rarely RHD affects the tricuspid valve directly; resulting in stenosis with TR. Involvement of both mitral and aortic valves is almost pathognomonic of RHD etiology. Severity of individual lesions may be difficult to ascertain as proximal valve lesion tends to modify the assessment of the distal valve lesion. It is important to understand that all valvular lesions do not require surgery. Regular secondary prophylaxis with long acting penicillin (for patients with RHD) may retard further progression of valve lesion and must be emphasized to the family. For mild and asymptomatic moderate valvular lesions, periodic monitoring with clinical examination and echocardiography is sufficient. No guidelines are available for timing of intervention in such children; data may have to be extrapolated from published guidelines for adult patients. Various types of surgical options are available for regurgitant valves, but none is ideal. The pediatricians are required to have knowledge of valvular diseases so as to refer the patient at an appropriate time for intervention or further evaluation. His/ her role is also crucial in follow up of post operated patients, especially those on oral anticoagulation. PMID- 26138579 TI - Omphalocele, Inguino-scrotal Hernia and Primary Pulmonary Hypertension: A Rare Combination in a Neonate. PMID- 26138580 TI - A preliminary study of the effects of working memory training on brain function. AB - Working memory (WM) training improves WM ability in Attention Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (CogmedTM) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts. PMID- 26138581 TI - Glucocorticoid-induced osteoporosis management among seniors, by year, sex, and indication, 1996-2012. AB - We identified that glucocorticoid-induced osteoporosis management (bone mineral density testing or osteoporosis treatment) among seniors improved among men (2 to 23 %) and women (10 to 48 %) between 1996 and 2007, and then remained relatively stable through to 2012. Differences were also noted by indication (from a low of 21 % for respiratory conditions to a high of 41 % for rheumatic conditions). PURPOSE: The aim of our study was to describe the proportion of chronic oral glucocorticoid (GC) users that receive osteoporosis management (bone mineral density test or osteoporosis treatment) by sex and over time. METHODS: We identified community-dwelling older adults initiating chronic oral GC therapy in Ontario using pharmacy data from 1996 to 2012. Chronic GC use was defined as greater than or equal to two oral GC prescriptions dispensed and >=450 mg prednisone equivalent over a 6-month period. Osteoporosis management within 6 months of starting chronic GC therapy was examined by sex, year, indication for therapy, and osteoporosis management history. Results were summarized using descriptive statistics. RESULTS: We identified 72,099 men and 95,975 women starting chronic oral GC therapy (mean age = 74.9 years, SD = 6.5). Approximately two thirds of patients (65 %) received >=900 mg within the 6-month chronic use window. GC-induced osteoporosis management increased from 2 to 23 % (men) and 10 to 48 % (women) between 1996 and 2007, and then remained relatively stable through to 2012. A higher proportion of patients with prior osteoporosis management were managed within 6 months (56 % men, 67 % women) of chronic GC use, compared to patients without prior management (12 % men, 23 % women). Patients with rheumatic disease were managed most commonly (41 %), and patients with respiratory conditions were managed least commonly (21 %). CONCLUSIONS: GC induced osteoporosis management improved significantly over time for both sexes yet remains low. Significant care gaps by sex and between clinical areas represent a missed opportunity for fracture prevention among patients requiring chronic GC therapy. PMID- 26138582 TI - The utility of lumbar spine trabecular bone score and femoral neck bone mineral density for identifying asymptomatic vertebral fractures in well-compensated type 2 diabetic patients. AB - The objective of the study was to evaluate the usefulness of trabecular bone score (TBS) and bone mineral density (BMD) for identifying vertebral fractures (VFx) in well-compensated type 2 diabetic (T2D) patients. TBS and femoral neck BMD below certain cutoffs may be useful for identifying VFx in well-compensated T2D patients. INTRODUCTION: In T2D, the prevalence of VFx is increased, especially in poorly compensated and complicated diabetic patients. The possibility of predicting the fracture risk in T2D patients by measuring BMD and TBS, an indirect parameter of bone quality, is under debate. Therefore, the objective was to evaluate the usefulness of TBS and BMD for identifying VFx in well-compensated T2D patients. METHODS: Ninety-nine T2D postmenopausal women in good metabolic control (glycosylated haemoglobin 6.8 +/- 0.7 %) and 107 control subjects without T2D were evaluated. In all subjects, we evaluated the following: the BMD at the lumbar spine (LS) and the femoral neck (FN); the TBS by dual X-ray absorptiometry; and VFx by radiography. In T2D subjects, the presence of diabetic retinopathy, neuropathy, and nephropathy was evaluated. RESULTS: T2D subjects had increased VFx prevalence (34.3 %) as compared to controls (18.7 %) (p = 0.01). T2D subjects presented higher BMD (LS -0.8 +/- 1.44, FN -1.06 +/- 1.08), as compared to controls (LS -1.39 +/- 1.28, p = 0.002; FN -1.45 +/- 0.91, p = 0.006, respectively). TBS was not different between diabetics and controls. In fractured T2D patients, LS-BMD, FN-BMD, and TBS were reduced (-1.2 +/- 1.44; -1.44 +/- 1.04; 1.072 +/- 0.15) and the prevalence of retinopathy (15.4 %) was increased than in nonfractured T2D subjects (-0.59 +/- 1.4, p = 0.035; -0.87 +/- 1.05, p = 0.005; 1.159 +/- 0.15, p = 0.006; 1.8 %, p = 0.04, respectively). The combination of TBS <=1.130 and FN-BMD less than -1.0 had the best diagnostic accuracy for detecting T2D fractured patients (SP 73.8 %, SN 63.6 %, NPV 78.9 %, PPV 56.8 %). CONCLUSIONS: TBS and FN-BMD below certain cutoffs may be useful for identifying VFx in well-compensated T2D patients. PMID- 26138583 TI - Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2 year prospective observational study. AB - Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. This is the first study reporting the use of bisphosphonates in patients with Bruck syndrome (BS). INTRODUCTION: OI and BS are genetic disorders that result in bone fragility and reduced BMD. There is little literature describing the efficacy and safety of ZA in this population. In this study, we assess the response to treatment with ZA at six monthly intervals in Egyptian children with OI and BS for a period of 2 years. METHODS: Thirty-three patients with OI and five patients with BS were treated with 0.1 mg/kg ZA intravenously every 6 months for 2 years during which they were followed up using different parameters. A clinical severity score (CSS) was applied to the patients before and 2 years after the start of therapy. Comparison of disease severity and response to ZA treatment between autosomal-dominant (AD) and autosomal-recessive (AR) OI patients was also done. RESULTS: After 6 months of treatment, OI and BS patients showed a significant increase in BMD Z-scores (P < 0.003 in the spine and P < 0.004 in the hip), together with a significant drop in fracture rate (P < 0.001), relief of pain (P < 0.001), and improvement in ambulation (P < 0.001). CSS was significantly reduced after 2 years of treatment in both OI and BS patients. AR-OI patients were more severely affected than AD-OI patients and showed more significant improvement. CONCLUSION: Zoledronic acid proved to be safe and effective in the treatment of OI and BS. The biannual infusion protocol was convenient to patients. There was a positive correlation between disease severity and benefits of the treatment. The use of the CSS proved to be of value in the assessment of the degree of severity in OI, and with some modifications, it was a valuable tool for the assessment of response to treatment. PMID- 26138584 TI - Plakophilin 1-deficient cells upregulate SPOCK1: implications for prostate cancer progression. AB - Plakophilin (PKP) 1 is frequently downregulated in prostate cancer and therefore may play a tumor-suppressive role. In the present study, we stably knocked down PKP1 in the non-neoplastic, prostatic BPH-1 cell line. In the PKP1-deficient cells, the expression of keratin 14 was lost, and the apoptosis rate was significantly reduced indicating that the cells acquired new biological capabilities. Moreover, we analyzed the gene expression profile of the PKP1 deficient BPH-1 cells. Among the genes that were significantly altered upon PKP1 knockdown, we noticed several extracellular matrix (ECM)-related genes and identified sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1/testican-1) as a gene of interest. SPOCK1 is a component of the ECM and belongs to a matricellular protein family named secreted protein, acidic, cysteine-rich (SPARC). The role of SPOCK1 in prostate cancer has not been clearly elucidated. We analyzed SPOCK1 mRNA expression levels in different cancer databases and characterized its expression in 136 prostatic adenocarcinomas by immunohistochemistry and western blot. SPOCK1 revealed a cytoplasmic localization in the glandular epithelium of the prostate and showed a significant upregulation of mRNA and protein in prostate tumor samples. Our findings support the hypothesis that PKP1 may have a tumor-suppressive function and suggest an important role of SPOCK1 in prostate tumor progression. Collectively, altered expression of PKP1 and SPOCK1 appears to be a frequent and critical event in prostate cancer. PMID- 26138585 TI - Corticotropin-releasing factor mediates bone cancer induced pain through neuronal activation in rat spinal cord. AB - Corticotropin-releasing factor (CRF) serves as a neuromodulator in the hypothalamic-pituitary-adrenal axis, playing an essential role in depression, anxiety, and pain regulation. However, its biological role in bone cancer induced pain has not been investigated. In the present study, we aimed to elucidate the expression and distribution of CRF in spinal cord using a rodent model of bone cancer pain. Our study showed that implantation of Walker 256 mammary gland carcinoma cells into the tibia of rats significantly increased CRF expression in the spinal cord in a time-dependent manner. The upregulated expression of CRF mainly expressed in the superficial dorsal horn of spinal cord. Moreover, immunofluorescence double staining showed that CRF was extensively colocalized with neurons, but hardly with astrocytes or microglia. In addition, intrathecal injection of CRF receptor antagonist (alpha-helical-CRF) significantly inhibited heat hyperalgesia, mechanical allodynia, and the expression of c-Fos in spinal dorsal horn of bone cancer pain rats. In summary, our study demonstrates that CRF plays an important role in the development and maintenance of bone cancer pain via activation of neurons. PMID- 26138586 TI - Integrative functional genetic-epigenetic approach for selecting genes as urine biomarkers for bladder cancer diagnosis. AB - Early screening for bladder cancer (BC) holds the key to combat and control the increasing global burden of BC mortality. We presented a simple approach to characterize, analyze, and validate a panel of biomarkers in BC and their relationship to bilharziasis. We investigated voided urine and blood samples from patients with bladder cancer (n = 94), benign bladder lesions (n = 60), and age matched normal controls (n = 56). This study was divided into the following phases. (1) We analyzed the expression of urinary Hyaluronoglucosaminidase 1 (HYAL1) protein in BC and control samples by zymography. (2) We performed bioinformatics analysis to retrieve a set of epigenetic regulators of HYAL1. (3) This set of three selected genes [long non-coding RNA-urothelial cancer associated 1(lncRNA-UCA1), microRNA-210, and microRNA-96] was then analyzed in the same urine samples used in phase I by quantitative real-time PCR. (4) A high reproducibility of gene selection results was also determined from statistical validation. The urinary expression of HYAL1 protein and its epigenetic regulators were higher in BC patients (P < .001). The receiver-operating characteristic curve analyses demonstrated that each one had good sensitivity and specificity for distinguishing BC patients from non-BC ones (HYAL1, 89.4 and 91.2 %; miR-210, 76.6 and 93 %; miR-96, 76.6 and 89.4 %; and lncRNA-UCA1, 91.5 and 96.5 %). There was a significant positive correlation between HYAL1 and the selected epigenetic biomarkers. The performance of this urine biomarker panel reached 100 % sensitivity and 89.5 % specificity for bladder cancer diagnosis. PMID- 26138587 TI - Growth of glioblastoma is inhibited by miR-133-mediated EGFR suppression. AB - Glioblastoma multiforme (GBM) is a severe and highly lethal brain cancer, which malignancy largely stems from its growing in a relatively restrained area in the brain. Hence, the understanding of the molecular regulation of the growth of GBM is critical for improving its treatment. Dysregulation of microRNAs (miRNAs) has recently been shown to contribute to the development of GBM, whereas the role of miR-133 in GBM is unknown. Here, by qualitative reverse transcription polymerase chain reaction (RT-qPCR), we detected lower miR-133 levels in GBM tissues, compared to the paired normal brain tissue. We overexpressed or inhibited miR-133 in GBM cells. Cell growth and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. We found that overexpression of miR-133 decreased GBM cell growth and increased cell apoptosis, while depletion of miR-133 increased cell growth and decreased cell apoptosis. Bioinformatic analysis was performed, showing that miR-133 may target the 3'-untranslated region (3'-UTR) of the epidermal growth factor receptor (EGFR) that transduces cell growth signals. Further, the protein translation inhibition of EGFR by miR-133 was confirmed by a dual luciferase reporter assay. Together, these data suggest that reduced miR-133 levels in GBM tissues promotes cell growth and decreases cell apoptosis, possibly through targeting mRNA of EGFR to suppress its translation. PMID- 26138588 TI - SmedGD 2.0: The Schmidtea mediterranea genome database. AB - Planarians have emerged as excellent models for the study of key biological processes such as stem cell function and regulation, axial polarity specification, regeneration, and tissue homeostasis among others. The most widely used organism for these studies is the free-living flatworm Schmidtea mediterranea. In 2007, the Schmidtea mediterranea Genome Database (SmedGD) was first released to provide a much needed resource for the small, but growing planarian community. SmedGD 1.0 has been a depository for genome sequence, a draft assembly, and related experimental data (e.g., RNAi phenotypes, in situ hybridization images, and differential gene expression results). We report here a comprehensive update to SmedGD (SmedGD 2.0) that aims to expand its role as an interactive community resource. The new database includes more recent, and up-to date transcription data, provides tools that enhance interconnectivity between different genome assemblies and transcriptomes, including next-generation assemblies for both the sexual and asexual biotypes of S. mediterranea. SmedGD 2.0 (http://smedgd.stowers.org) not only provides significantly improved gene annotations, but also tools for data sharing, attributes that will help both the planarian and biomedical communities to more efficiently mine the genomics and transcriptomics of S. mediterranea. PMID- 26138589 TI - Generation of alpha-1,3-Galactosyltransferase-Deficient Porcine Embryonic Fibroblasts by CRISPR/Cas9-Mediated Knock-in of a Small Mutated Sequence and a Targeted Toxin-Based Selection System. AB - The CRISPR/Cas9 system has enabled the editing of mammalian genomes; however, its applicability and efficiency in the pig genome has not been studied in depth. The alpha-gal epitope synthesized by alpha-1,3-galactosyltransferase gene (GGTA1) is known as a xenoantigen obtained upon pig-to-human xenotransplantation. We here employed the CRISPR/Cas9 system-mediated knock-in of endogenous GGTA1 via targeted homologous recombination (HR). Linearized donors with ~800-bp homology flanking the CRISPR/Cas9 target site [exon 4 (containing ATG) of GGTA1] served as a template for gene targeting by HR. Using a targeted toxin strategy to select clones lacking alpha-gal epitope expression, we successfully obtained several knock-in clones within 3 weeks of initial transfection. These results suggest that the use of CRISPR/Cas9-mediated HR to knock-in a mutated fragment at defined loci represents an efficient strategy to achieve the rapid modulation of genes of interest in swine cells and is a promising tool for the creation of KO piglets. PMID- 26138590 TI - Diagnostic errors of right lower quadrant pain in children: beyond appendicitis. AB - Right lower quadrant pain in children can result from various underlying conditions other than acute appendicitis. The common mimics of acute appendicitis are related to acute gastrointestinal and genitourinary diseases. Diagnosis of right lower quadrant pain in the pediatric population can be challenging, especially when the symptoms are often nonspecific. This article reviews the currently available imaging techniques for evaluating a child with right lower quadrant pain and the spectrum of differential diagnoses with a focus on imaging clues to a specific diagnosis. PMID- 26138591 TI - Behavioural ecology cannot turn its back on Levy walk research: Comment on "Liberating Levy walk research from the shackles of optimal foraging" by A.M. Reynolds. PMID- 26138592 TI - Unifying perspectives on cooperation under social viscosity: Comment on "Universal scaling for the dilemma strength in evolutionary games" by Z. Wang et al. PMID- 26138594 TI - Bidirectional Glenn With Additional Pulmonary Blood Flow: Systematic Review and Evidence-Based Recommendations. AB - The aim of this report was to review the exiting literature to date to inform clinical decision-making regarding the additional pulmonary blood flow at the time of bidirectional Glenn procedure. PMID- 26138593 TI - The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to severe rheumatoid arthritis and an inadequate response to methotrexate: results from a multinational, phase IIb, randomized, double-blind, placebo/active controlled, dose-ranging study. AB - OBJECTIVE: Clazakizumab is a humanized monoclonal antibody that binds to the interleukin-6 (IL-6) cytokine. This study was undertaken to evaluate the efficacy and safety of clazakizumab in combination with methotrexate (MTX) or clazakizumab monotherapy versus MTX alone in patients with rheumatoid arthritis (RA) and an inadequate response to MTX. METHODS: In this multinational, phase IIb, randomized, double-blind, placebo-controlled, dose-ranging study, patients were randomized to receive 1) once-monthly subcutaneous (SC) clazakizumab at 25, 100, or 200 mg plus MTX, 2) once-monthly SC clazakizumab at 100 mg or 200 mg as monotherapy, or 3) MTX plus placebo (i.e., MTX alone). Adalimumab (40 mg) plus MTX was included as an active reference. The primary end point was the American College of Rheumatology 20% (ACR20) improvement response rate at week 12. Secondary end points included ACR20, ACR50, and ACR70 response rates as well as protocol-defined remission rates and Health Assessment Questionnaire disability index scores at weeks 12 and 24. RESULTS: In total, 418 patients were randomized, and baseline characteristics were balanced across the treatment groups. Patients receving clazakizumab had significantly greater ACR20 response rates at week 12 compared with patients receiving MTX alone (76.3%, 73.3%, and 60.0% of patients in the clazakizumab 25, 100, and 200 mg plus MTX groups, respectively, and 55.0% and 61.0% of patients in the clazakizumab 100 and 200 mg monotherapy groups, respectively, versus 39.3% of patients receiving MTX alone; P < 0.05 for all comparisons). At week 24, all clazakizumab groups had higher ACR20, ACR50, and ACR70 response rates and higher remission rates compared with MTX alone. Rates of serious adverse events ranged from 8.3% to 13.6% in the clazakizumab treatment groups, compared with 3.3% in the MTX alone group. Changes in laboratory data were consistent with the pharmacologic effects of IL-6 blockade. CONCLUSION: In patients with RA and an inadequate response to MTX, treatment with clazakizumab in combination with MTX or clazakizumab monotherapy was well tolerated, and patients achieved significant improvements in disease activity, including higher rates of remission, as compared with patients receiving MTX alone. PMID- 26138595 TI - Adhesion characterization and defect sizing of sandwich honeycomb composites. AB - Defects may appear in composite structures during their life cycle. A 10MHz 128 elements phased array transducer was investigated to characterize join bonds and defects in sandwich honeycomb composite structures. An adequate focal law throughout the composite skin gives the ultrasonic dispersive properties of the composite skin and glue layer behind. The resulting B-scan cartographies allow characterizing locally the honeycomb adhesion. Experimental measurements are compared in good agreement with the Debye Series Method (DSM). In the processed C scan image, flaws are detectable and measurable, localized both in the scanning plane and in the thickness of the composite skin. PMID- 26138596 TI - Effect of initial stress on propagation behaviors of shear horizontal waves in piezoelectric/piezomagnetic layered cylinders. AB - An analytical approach is taken to investigate shear horizontal wave (SH wave) propagation in layered cylinder with initial stress, where a piezomagnetic (PM) material thin layer is bonded to a piezoelectric (PE) cylinder. Two different material combinations are taken into account, and the phase velocities of the SH waves are numerically calculated for the magnetically open and short cases, respectively. It is found that the initial stress, the thickness ratio and the material performance have a great influence on the phase velocity. The results obtained in this paper can offer fundamental significance to the application of PE/PM composite media or structure for the acoustic wave and microwave technologies. PMID- 26138597 TI - Red selenium nanoparticles and gray selenium nanorods as antibacterial coatings for PEEK medical devices. AB - Bacterial infections are commonly found on various poly(ether ether ketone) (PEEK) medical devices (such as orthopedic instruments, spinal fusion devices, and segments in dialysis equipment), and thus, there is a significant need for introducing antibacterial properties to such materials. The objective of this in vitro study was to introduce antibacterial properties to PEEK medical devices by coating them with nanosized selenium. In this study, red selenium (an elemental form of selenium) nanoparticles were coated on PEEK medical devices through a quick precipitation method. Furthermore, with heat treatment at 100 degrees C for 6 days, red selenium nanoparticles were transferred into gray selenium nanorods on the PEEK surfaces. Bacteria test results showed that both red and gray selenium-coated PEEK medical devices significantly inhibited the growth of Pseudomonas aeruginosa compared with uncoated PEEK after either 1, 2, or 3 days. Red selenium nanoparticle-coated PEEK showed less bacteria growth on its surface than gray selenium nanorod-coated PEEK after 3 days. This study demonstrated that red, and to a lesser extent gray, nanosized selenium could be used as potential antibacterial coatings to prevent bacteria function on PEEK medical devices. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1352 1358, 2016. PMID- 26138598 TI - Staged Catheter-Based Valve Treatment of Severe Carcinoid Heart Disease. AB - PURPOSE: Carcinoid heart disease (CHD) with severe valve destruction represents the major cause of high morbidity and mortality in patients with carcinoid syndrome. In this paper, we present a novel interventional treatment approach and report the first clinical result achieved in a patient with extensive CHD. METHODS AND RESULTS: A woman with an ileal neuroendocrine tumour (G2, Ki67: 5%) presented with severe CHD (NYHA IV) affecting both the pulmonary and the tricuspid valve. First, a balloon-expandable 23-mm Edwards SAPIENTM was successfully implanted percutaneously into the pulmonary valve. Since no catheter based techniques were available for the replacement of the native tricuspid valve, we implanted an Edwards SAPIEN 26-mm valve into the vena cava inferior between the right atrium and the ostium of the hepatic veins to reduce abdominal congestion. The implantation was technically successful and completely prevented regurgitation into the vena cava inferior and abdominal veins. After this procedure, the patient's clinical condition improved significantly, and she achieved near-normal exercise tolerance (VO2 max: 24.4 ml O2/kg/min, NYHA II). CONCLUSION: We demonstrated that percutaneous valve implantation may offer a novel, minimally invasive option in high-risk patients with severe CHD. PMID- 26138599 TI - Quantifying the importance of disease burden on perceived general health and depressive symptoms in patients within the Mayo Clinic Biobank. AB - BACKGROUND: Deficits in health-related quality of life (HRQOL) may be associated with worse patient experiences, outcomes and even survival. While there exists evidence to identify risk factors associated with deficits in HRQOL among patients with individual medical conditions such as cancer, it is less well established in more general populations without attention to specific illnesses. This study used patients with a wide range of medical conditions to identify contributors with the greatest influence on HRQOL deficits. METHODS: Self perceived general health and depressive symptoms were assessed using data from 21,736 Mayo Clinic Biobank (MCB) participants. Each domain was dichotomized into categories related to poor health: deficit (poor/fair for general health and >=3 for PHQ-2 depressive symptoms) or non-deficit. Logistic regression models were used to test the association of commonly collected demographic characteristics and disease burden with each HRQOL domain, adjusting for age and gender. Gradient boosting machine (GBM) models were applied to quantify the relative influence of contributors on each HRQOL domain. RESULTS: The prevalence of participants with a deficit was 9.5 % for perception of general health and 4.6 % for depressive symptoms. For both groups, disease burden had the strongest influence for deficit in HRQOL (63 % for general health and 42 % for depressive symptoms). For depressive symptoms, age was equally influential. The prevalence of a deficit in general health increased slightly with age for males, but remained stable across age for females. Deficit in depressive symptoms was inversely associated with age. For both HRQOL domains, risk of a deficit was associated with higher disease burden, lower levels of education, no alcohol consumption, smoking, and obesity. Subjects with deficits were less likely to report that they were currently working for pay than those without a deficit; this association was stronger among males than females. CONCLUSIONS: Comorbid health burden has the strongest influence on deficits in self-perceived general health, while demographic factors show relatively minimal impact. For depressive symptoms, both age and comorbid health burden were equally important, with decreasing deficits in depressive symptoms with increasing age. For interpreting patient-reported metrics and comparison, one must account for comorbid health burden. PMID- 26138600 TI - High-throughput screening of vitamins and natural antioxidants in nutraceuticals from green tea extracts by liquid chromatography coupled to quadrupole orbitrap mass spectrometry. AB - A new analytical method was developed and validated for simultaneous analysis of 52 vitamins and natural antioxidants in nutraceutical products obtained from green tea (Camellia sinensis) extracts. The automated extraction procedure was achieved in a simple disposable pipet extraction. Ultra-high performance liquid chromatography and electrospray ionization quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC Q-Orbitrap) was used for the separation and detection of all the analytes. The method was validated by taking into consideration the guidelines specified in European SANCO/12571/2013 Guideline 2013 and Commission Decision 2002/657/EC. The extraction recoveries were in a range of 84.9-112.7%, with coefficient of variation <6.4%. The limits of decision for the analytes were in the range of 0.05-1.91mgkg(-1). The detection capabilities for the analytes were in the range of 0.08-3.18mgkg(-1). The 52 compounds behave dynamic 0.2 200mgkg(-1), with correlation coefficient >0.99. This validated method has been successfully applied on screening of vitamins and natural antioxidants in 136 different commercial nutraceutical products from green tea extracts. PMID- 26138601 TI - A strategy for the separation of diterpenoid isomers from the root of Aralia continentalis by countercurrent chromatography: The distribution ratio as a substitute for the partition coefficient and a three-phase solvent system. AB - Aralia continentalis (Araliaceae) is widely used as a medicinal plant in East Asia. Previous studies have indicated that diterpenoid isomers (kaurenoic acid, continentalic acid, and ent-continentalic acid) are the major bioactive compounds of this plant. A new strategy was developed to alleviate difficulties in the separation of these isomers from this plant. A three-phase solvent system was applied to separate the isomers, and furthermore, the distribution ratio (Kc) was introduced as a substitute for the partition coefficient (KD). For compounds exhibiting a single equilibrium, their distributions in two immiscible phases were only affected by the partition coefficient of each solute. However, compounds that have a dissociating functional group (e.g., -COOH) are involved in two types of equilibrium in the two-phase system. In this case, the partitioning behaviors of the solutes are greatly affected by the pH of the solution. A mathematical prediction was applied for adjusting the solutions to the proper pH values. To prevent non-used phase (medium phase) waste, both the stationary phase (upper phase) and mobile phase (lower phase) were prepared on-demand without pre saturation with the application of (1)H NMR. Each fraction obtained was collected and dried, yielding the following diterpenoid isomers from the 50mg injected sample: kaurenoic acid (19.7mg, yield: 39%) and ent-continentalic acid (21.3mg, yield: 42%). PMID- 26138602 TI - Evaluation of fast enantioselective multidimensional gas chromatography methods for monoterpenic compounds: Authenticity control of Australian tea tree oil. AB - This work demonstrates the potential of fast multiple heart-cut enantioselective multidimensional gas chromatography (GC-eGC) and enantioselective comprehensive two-dimensional gas chromatography (eGC*GC), to perform the stereoisomeric analysis of three key chiral monoterpenes (limonene, terpinen-4-ol and alpha terpineol) present in tea tree oil (TTO). In GC-eGC, separation was conducted using a combination of mid-polar first dimension ((1)D) column and a chiral second dimension ((2)D) column, providing interference-free enantioresolution of the individual antipodes of each optically active component. A combination of (1)D chiral column and (2)D polar columns (ionic liquid and wax phases) were tested for the eGC*GC study. Quantification was proposed based on summation of two major modulated peaks for each antipode, displaying comparable results with those derived from GC-eGC. Fast chiral separations were achieved within 25min for GC-eGC and<20min for eGC*GC, while ensuring adequate interference-free enantiomer separation. The suitability of using these two enantioselective multidimensional approaches for the routine assessment of chiral monoterpenes in TTO was evaluated and discussed. Exact enantiomeric composition of chiral markers for authentic TTOs was proposed by analysing a representative number of pure TTOs sourced directly from plantations of known provenance in Australia. Consistent enantiomeric fractions of 61.6+/-1.5% (+):38.4+/-1.5% (-) for limonene, 61.7+/ 1.6% (+):38.3+/-1.6% (-) for terpinen-4-ol and 79.6+/-1.4% (+):20.4+/-1.4% (-) for alpha-terpineol were obtained for the 57 authentic Australian TTOs. The results were compared (using principle component analysis) with commercial TTOs (declared as derived from Melaleuca alternifolia) obtained from different continents. Assessing these data to determine adulteration, or additives that affect the enantiomeric ratios, in commercially sourced TTOs is discussed. The proposed method offers distinct advantages over eGC, especially in terms of analysis times and selectivity which can serve as a reliable platform for authenticity control of TTO. PMID- 26138603 TI - Cyclodextrin clicked chiral stationary phases with functionalities-tuned enantioseparations in high performance liquid chromatography. AB - In this work, two cyclodextrin (CD) chiral stationary phases (CSPs) have been developed by clicking per-4-chloro-3-methylphenylcarbamoylated mono-6(A)-azido beta-CD (CSP1) and per-5-chloro-2-methylphenylcarbamoylated mono-6(A)-azido-beta CD (CSP2) onto alkynylated silica support. The enantioslectivies of the as obtained new CSPs have been evaluated using 29 model racemates including aromatic alcohols, flavonoids, beta-blocker and FMOC-amino acids in both reversed-phase (RP) and normal-phase (NP) high performance liquid chromatography (HPLC). The CD functionalities tuned enantioselectivities were elucidated in different HPLC elution modes. Higher chiral resolutions were achieved in RP-elution mode with the aid of the inclusion complexation in comparison to NP-elution mode. The pi-pi stacking interaction and dipole-dipole interaction provided by phenylcarbamate moieties can also contribute to the enantioseparation. PMID- 26138604 TI - A solid-phase microextraction platinized stainless steel fiber coated with a multiwalled carbon nanotube-polyaniline nanocomposite film for the extraction of thymol and carvacrol in medicinal plants and honey. AB - A mechanically hard and cohesive porous fiber, with large surface area, for more strong attachment of the coating was provided by platinizing a stainless steel wire. Then, the platinized stainless steel fiber was coated with a multiwalled carbon nanotube/polyaniline (MWCNT/PANI) nanocomposite using electrophoretic deposition (EPD) method and applied for the extraction of thymol and carvacrol with direct-immersion solid-phase microextraction (DI-SPME) method followed by high-performance liquid chromatography-ultraviolet detection (HPLC-UV) quantification. To provide a larger coarse surface for the tightened attachment of coating on the fiber, a stainless steel wire was platinized using a suitable optimized EPD method. Different experimental parameters were studied and the optimal conditions were obtained as: pH of the sample solution: 2; extraction time: 60min; salt content in the sample solution: 1% w/v NaNO3; desorption time: 60min; type and volume of the desorption solvent: acetonitrile, 100MUL. Under the optimized conditions, limits of detection (LODs) were 0.6 and 0.8MUgmL(-1) for thymol and carvacrol, respectively. Linear dynamic range (LDR) for the calibration curves of both analytes were 1-80MUgmL(-1). Relative standard deviation (RSD%, n=6) was 6.8 for thymol and 12.7 for carvacrol. The proposed fiber was successfully applied for the recovery and determination of thymol and carvacrol in thyme, savory, and honey samples. PMID- 26138605 TI - Development and Validation of a High-Fidelity Porcine Laryngeal Surgical Simulator. AB - OBJECTIVE: Design and validate a laryngeal surgical simulator to teach phonomicrosurgical techniques. STUDY DESIGN: Device development and prospective validation. SETTING: Tertiary medical center. SUBJECTS AND METHODS: A novel laryngeal fixation device and custom laryngoscope were produced for use with ex vivo porcine larynx specimens. Vocal fold lesions such as nodules and keratotic lesions were simulated with silicone injections and epithelial markings. A prospective validation using postsimulation surveys, global rating scales, and procedure-specific checklists was performed with a group of 15 medical students, otolaryngology residents, fellows, and attending laryngologists. Three procedures were performed: vocal fold augmentation, excision of a simulated vocal fold nodule, and excision of a simulated vocal fold keratosis. RESULTS: Participants overwhelmingly agreed that the simulator provided a realistic dissection experience that taught skills that would transfer to real operating scenarios. Expert performance was statistically superior to novice performance for excision of simulated vocal fold nodules and keratotic lesions, while no difference was observed for injection laryngoplasty. CONCLUSION: The ability to learn and rehearse surgical procedures in a safe environment is invaluable, particularly for delicate and highly technical phonomicrosurgical operations. We have developed a high-fidelity laryngeal surgical simulator complete with pathological lesions such as nodules and keratoses to teach these procedures. A prospective study demonstrated validity of our global rating scale and checklist assessments for vocal fold nodule and keratosis excision procedures, allowing them to be confidently incorporated into phonomicrosurgical training programs for surgeons of all levels of expertise. PMID- 26138607 TI - Shoulder Dysfunction after Selective Neck Dissection in Recurrent Nasopharyngeal Carcinoma. AB - OBJECTIVE: To investigate the incidence of occult nodal metastasis and severity of shoulder dysfunction after selective neck dissection (SND) for recurrent nasopharyngeal carcinoma (NPC) with N0 status. STUDY DESIGN: Prospective, single group, pre/post test design. SETTING: Academic medical center. SUBJECTS AND METHODS: Between 1998 and 2012, 46 patients who had recurrent NPC and N0 status were recruited. They subsequently received salvage nasopharyngectomy and SND, removing ipsilateral level I to III and V lymphatics. The incidence of occult nodal metastasis was noted. All patients underwent standardized physiotherapy after surgery. Postoperative shoulder function was measured using the Disability of Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS: The incidence of microscopic nodal metastasis was 15.2%. For first year posttreatment, the mean DASH score was 44.2. With time, there was no improvement in shoulder function despite targeted physiotherapy (P = .09), and the second postoperative year mean DASH score was 46.3. The degree of daily activity affected was rated as moderate to very limited, and 30% of the patients had at least moderate shoulder pain at rest. CONCLUSION: Shoulder dysfunction after SND for recurrent NPC is significant and persistent. Given the low incidence of microscopic nodal metastasis in such circumstances, routine SND is not recommended. PMID- 26138608 TI - Device characterization and optimization of small molecule organic solar cells assisted by modelling simulation of the current-voltage characteristics. AB - In order to understand the photovoltaic performance differences between the recently reported DR3TBTT-HD and DR3TBDT2T based solar cells, a modified two diode model with Hecht equation was built to simulate the corresponding current voltage characteristics. The simulation results reveal that the poor device performance of the DR3TBDTT-HD based device mainly originated from its insufficient charge transport ability, where an average current of 5.79 mA cm(-2) was lost through this pathway at the maximum power point for the DR3TBDTT-HD device, nearly three times as large as that of the DR3TBDT2T based device under the same device fabrication conditions. The morphology studies support these simulation results, in which both Raman and 2D-GIXD data reveal that DR3TBTT-HD based blend films exhibit lower crystallinity. Spin coating at low temperature was used to increase the crystallinity of DR3TBDTT-HD based blend films, and the average current loss through insufficient charge transport at maximum power point was suppressed to 2.08 mA cm(-2). As a result, the average experimental power conversion efficiency of DR3TBDTT-HD based solar cells increased by over 40%. PMID- 26138606 TI - Neural Response Telemetry Thresholds in Patients with Cochlear Nerve Canal Stenosis. AB - OBJECTIVE: To explore neural response telemetry (NRT) thresholds in patients with stenotic versus normal cochlear nerve canals. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Thirty pediatric patients with profound sensorineural hearing loss in at least 1 ear and no benefit from amplification underwent computed tomography imaging of the temporal bones. They were divided into 3 groups according to the diameter of the cochlear nerve canal: group A, <1.5 mm; group B, 1.5 to 1.7 mm; group C, 1.8 to 2.1 mm. All patients underwent cochlear implantation with full insertion of all electrodes. NRT was performed both intraoperatively and 6 months postoperatively in all patients; thresholds of electrodes 1, 11, and 22 were compared. RESULTS: Per analysis of variance, intraoperative and 6-month postoperative NRT thresholds were both significantly different among groups A, B, and C at electrodes 1 and 22 but not at electrode 11. On intergroup analysis, group A showed statistically higher thresholds than those of groups B and C; however, no difference was found between groups B and C. CONCLUSION: Cochlear nerve canal stenosis, defined as a canal diameter <1.5 mm, is associated with significantly increased NRT thresholds, which may play a role in postimplant performance. PMID- 26138609 TI - Competencies for the new postdoctoral Oral Medicine graduate in the United States. AB - Oral Medicine is primarily a nonsurgical dental discipline that includes management of (1) oral mucosal and salivary gland diseases; (2) temporomandibular disorders and orofacial pain; (3) oral complications of systemic disease; and (4) dental management of medically complex patients within its scope of practice. In the United States, the American Academy of Oral Medicine (AAOM) is the professional organization that primarily supports Oral Medicine education, research, and patient care. This document informs the knowledge, skills, and behaviors of beginning Oral Medicine graduates in the United States in three domains: Diagnosis and primarily nonsurgical management of oral mucosal and salivary gland disorders. Diagnosis and primarily nonsurgical management of temporomandibular, orofacial pain, and neurosensory disorders. Management of the medically complex patient. Each domain is subsequently expanded with major competencies and supporting competencies. PMID- 26138610 TI - A topographical organization for action representation in the human brain. AB - How the human brain represents distinct motor features into a unique finalized action still remains undefined. Previous models proposed the distinct features of a motor act to be hierarchically organized in separated, but functionally interconnected, cortical areas. Here, we hypothesized that distinct patterns across a wide expanse of cortex may actually subserve a topographically organized coding of different categories of actions that represents, at a higher cognitive level and independently from the distinct motor features, the action and its final aim as a whole. Using functional magnetic resonance imaging and pattern classification approaches on the neural responses of 14 right-handed individuals passively watching short movies of hand-performed tool-mediated, transitive, and meaningful intransitive actions, we were able to discriminate with a high accuracy and characterize the category-specific response patterns. Actions are distinctively coded in distributed and overlapping neural responses within an action-selective network, comprising frontal, parietal, lateral occipital and ventrotemporal regions. This functional organization, that we named action topography, subserves a higher-level and more abstract representation of finalized actions and has the capacity to provide unique representations for multiple categories of actions. PMID- 26138611 TI - Highly E-Selective and Enantioselective Michael Addition to Electron-Deficient Internal Alkynes Under Chiral Iminophosphorane Catalysis. AB - A highly E-selective and enantioselective conjugate addition of 2 benzyloxythiazol-5(4H)-ones to beta-substituted alkynyl N-acyl pyrazoles is achieved under the catalysis of a P-spiro chiral iminophosphorane. Simultaneous control of the newly generated central chirality and olefin geometry is possible with a wide array of the alkynyl Michael acceptors possessing different aromatic and aliphatic beta-substituents, as well as the various alpha-amino acid-derived thiazolone nucleophiles. This protocol provides access to structurally diverse, optically active alpha-amino acids bearing a geometrically defined trisubstituted olefinic component at the alpha-position. PMID- 26138612 TI - In Vitro Hepatic Oxidative Biotransformation of Trimethoprim. AB - Trimethoprim (TMP) has been widely used since the 1960s, both alone and in combination with sulfamethoxazole. Unfortunately, information regarding the role that cytochrome P450 enzymes (P450s) play in the formation of TMP primary metabolites is scarce. Hence, we undertook in vitro studies to identify and more fully characterize the P450s that catalyze formation of six TMP primary metabolites: TMP 1-N-oxide (1-NO-TMP) and 3-N-oxide (3-NO-TMP), 3'- and 4' desmethyl-TMP, a benzylic alcohol (Calpha-OH-TMP), and an N-acetyl cysteine (NAC) adduct of TMP (Calpha-NAC-TMP). Formation kinetics for each TMP metabolite in human liver microsomes (HLMs) were consistent with single-enzyme Michaelis-Menten kinetics, and Km values were markedly above (>=10-fold) the therapeutic concentrations of TMP (50 uM). The combined results from correlation studies between rates of metabolite formation and marker P450 activities in a panel of HLMs along with inhibition studies utilizing selective P450 inhibitors incubated with pooled HLMs suggested that 1-NO-TMP, Calpha-NAC-TMP, and Calpha-OH-TMP were predominantly formed by CYP3A4. In contrast, 3-NO-TMP was formed predominantly by CYP1A2 in HLMs and inhibited by alpha-naphthoflavone. 4'-Desmethyl-TMP, which is believed to be a reactive TMP metabolite precursor, was formed by several P450s, including CYP3A4, correlated with multiple P450 activities, but was inhibited primarily by ketoconazole (up to 50%), suggesting that CYP3A4 makes a major contribution to TMP 4'-demethylation. TMP 3'-demethylation was catalyzed by multiple P450s, including CYP2C9, correlated with CYP2C9 activity, and was inhibited by sulfaphenazole (up to 40%). Overall, CYP2C9 and CYP3A4 appear to be the most significant contributors to TMP primary metabolism. PMID- 26138614 TI - Breastfeeding and infant growth. PMID- 26138613 TI - Choroidal thickness and high myopia: a cross-sectional study and meta-analysis. AB - BACKGROUND: The purpose of this study was to examine the choroidal thickness of patients with high myopia using enhanced depth imaging optical coherence tomography (EDI-OCT) and compare them with healthy subjects. METHODS: We first conducted a cross-sectional study and then performed a meta-analysis to address this issue further. Using enhanced depth imaging optical coherence tomography (EDI-OCT), the macular choroidal thickness of high myopic eyes and normal control eyes were measured and compared at each location. Univariate and multivariate linear regression analyses were performed to assess the association between choroidal thickness and clinical factors such as axial length (AL), spherical equivalent (SE), and central corneal thickness. In the high myopic eyes, subgroup analysis of macular choroidal thickness was performed in eyes with or without lacquer cracks and choroidal neovascularization (CNV). The meta-analyses were conducted using the Stata software package. RESULTS: The high myopic eyes had a thinner choroid than the control eyes at all macular locations (all P < 0.001). Multivariable linear regression analysis showed that the subfoveal choroidal thickness (SFCT) was not significantly thinner in association with the diagnosis. Subgroup analysis showed that the high myopia with CNV and with lacquer cracks had a significantly thinner choroid than without CNV or lacquer crack eyes. The result of our cross-sectional study is consistent with the results of the further meta-analysis with the pooled weighted mean difference (WMD) of -116.30 MUm (95 % CI: -145.68, -86.92) for SFCT. CONCLUSIONS: The present study, along with the comprehensive meta-analysis, indicated that in the Chinese population, the choroidal thickness in high myopic eyes was thinner than that of normal control eyes, even across different subgroups. This might be secondary to the longer AL but it is not an independent factor. The presence of CNV and of lacquer cracks is associated strongly with eyes with thinner macular choroids. PMID- 26138615 TI - Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia. AB - INTRODUCTION: Connective tissue growth factor (CTGF/CCN2) has been shown previously to be aberrantly expressed in a high proportion of paediatric precursor B cell acute lymphoblastic leukaemia (pre-B ALL), suggesting a potential oncogenic role in this tumour type. We therefore assessed CTGF mRNA transcript diversity in B-lineage ALL using primary patient specimens and cell lines. METHODS: CTGF mRNA expression was evaluated by quantitative real-time PCR and Northern blotting. We performed a structural analysis of CTGF mRNA by nested reverse-transcriptase PCR and examined CTGF protein diversity by immunoblotting. RESULTS: Northern blot analysis of pre-B ALL cell lines revealed short CTGF transcripts that were expressed in association with the active phase of cellular growth. Structural analysis confirmed the synthesis of several novel CTGF mRNA isoforms in B-lineage ALL cell lines that were uniformly characterised by the retention of the coding sequence for the C-terminal (CT) domain. One of these novel spliceforms was expressed in a majority (70%) of primary pre-B ALL patient specimens positive for canonical CTGF mRNA. Evidence that these alternative transcripts have coding potential was provided by cryptic CTGF proteins of predicted size detected by immunoblotting. CONCLUSION: This study identifies for the first time alternative splicing of the CTGF gene and shows that a short CTGF splice variant associated with cell proliferation is expressed in most cases of primary CTGF-positive pre-B ALL. This novel variant encoding only the CT domain may play a role in pre-B ALL tumorigenesis and/or progression. PMID- 26138616 TI - Sail or sink: novel behavioural adaptations on water in aerially dispersing species. AB - BACKGROUND: Long-distance dispersal events have the potential to shape species distributions and ecosystem diversity over large spatial scales, and to influence processes such as population persistence and the pace and scale of invasion. How such dispersal strategies have evolved and are maintained within species is, however, often unclear. We have studied long-distance dispersal in a range of pest-controlling terrestrial spiders that are important predators within agricultural ecosystems. These species persist in heterogeneous environments through their ability to re-colonise vacant habitat by repeated long-distance aerial dispersal ("ballooning") using spun silk lines. Individuals are strictly terrestrial, are not thought to tolerate landing on water, and have no control over where they land once airborne. Their tendency to spread via aerial dispersal has thus been thought to be limited by the costs of encountering water, which is a frequent hazard in the landscape. RESULTS: In our study we find that ballooning in a subset of individuals from two groups of widely-distributed and phylogenetically distinct terrestrial spiders (linyphiids and one tetragnathid) is associated with a hitherto undescribed ability of those same individuals to survive encounters with both fresh and marine water. Individuals that showed a high tendency to adopt 'ballooning' behaviour adopted elaborate postures to seemingly take advantage of the wind current whilst on the water surface. CONCLUSIONS: The ability of individuals capable of long-distance aerial dispersal to survive encounters with water allows them to disperse repeatedly, thereby increasing the pace and spatial scale over which they can spread and subsequently exert an influence on the ecosystems into which they migrate. The potential for genetic connectivity between populations, which can influence the rate of localized adaptation, thus exists over much larger geographic scales than previously thought. Newly available habitat may be particularly influenced given the degree of ecosystem disturbance that is known to follow new predator introductions. PMID- 26138617 TI - Identification and characterization of the adipokinetic hormone/corazonin-related peptide signaling system in Rhodnius prolixus. AB - The mammalian gonadotropin-releasing hormone is evolutionarily related to the arthropod adipokinetic hormone and the recently discovered adipokinetic hormone/corazonin-related peptide (ACP). The function of the ACP signaling system in arthropods is currently unknown. In the present study, we identify and characterize the ACP signaling system in the kissing bug Rhodnius prolixus. We isolated the complete cDNA sequence encoding R. prolixus ACP (Rhopr-ACP) and examined its expression pattern. Rhopr-ACP is predominantly expressed in the central nervous system. In particular, it is found in both the brain and corpus cardiacum (CC)/corpora allata (CA) complex. To gain an insight into its role in R. prolixus, we also isolated and functionally characterized cDNA sequences of three splice variants (Rhopr-ACPR-A, B and C) encoding R. prolixus ACP G protein coupled receptor (Rhopr-ACPR). Rhopr-ACPR-A has only five transmembrane domains, whereas Rhopr-ACPR-B and C have all seven domains. Interestingly, Rhopr-ACPR-A, B and C were all activated by Rhopr-ACP, albeit at different sensitivities, when expressed in Chinese hamster ovary cells stably expressing the human G-protein G16 (CHO/G16). To our knowledge, this is the first study to isolate a truncated receptor cDNA in invertebrates that is functional in a heterologous expression system. Moreover, Rhopr-ACPR-B and C but not Rhopr-ACPR-A can be coupled with Gq alpha subunits. Expression profiling indicates that Rhopr-ACPR is highly expressed in the central nervous system, as well as the CC/CA complex, suggesting that it may control the release of other hormones found in the CC in a manner analogous to gonadotropin-releasing hormone. Temporal expression profiling shows that both Rhopr-ACP and Rhopr-ACPR are upregulated after ecdysis, suggesting that this neuropeptide may be involved in processes associated with post-ecdysis. PMID- 26138618 TI - Assessment of Serum Copper State after Gastrectomy with Roux-en-Y Reconstruction for Gastric Cancer. AB - BACKGROUND: Some recent reports have noted that copper deficiency can occur in obese patients who have undergone bariatric surgery, such as Roux-en-Y (RY) gastric bypass or biliopancreatic diversion, or in patients who receive enteral nutrition through a jejunostomy. No reports appear to have assessed the serum copper state of patients following gastrectomy with RY reconstruction for gastric cancer. METHODS: A cross-sectional study was conducted from June 2013 to December 2014. Serum copper levels (SCLs) in 242 out-clinic patients who underwent curative gastrectomy were obtained. Patients were classified into an RY group (n = 208) and a non-RY group (n = 34). RESULTS: Hypocupremia was identified in 3 patients in the RY group (1.4%), and 2 patients in the non-RY group (5.9%; p = 0.146), but none experienced any symptoms caused by hypocupremia. No significant difference in the mean SCL was seen between the RY group (105.8 +/- 21.2 ug/dl) and non-RY group (107.9 +/- 22.7 ug/dl; p = 0.499). In the RY group, the mean SCL was significantly lower in younger patients, patients with follow-up period <3 years, and male patients. CONCLUSION: Some patients developed hypocupremia after gastrectomy with RY reconstruction, but the number is acceptably low, and physical symptoms were unusual. PMID- 26138619 TI - Hot electron-induced reduction of small molecules on photorecycling metal surfaces. AB - Noble metals are important photocatalysts due to their ability to convert light into chemical energy. Hot electrons, generated via the non-radiative decay of localized surface plasmons, can be transferred to reactants on the metal surface. Unfortunately, the number of hot electrons per molecule is limited due to charge carrier recombination. In addition to the reduction half-reaction with hot electrons, also the corresponding oxidation counter-half-reaction must take place since otherwise the overall redox reaction cannot proceed. Here we report on the conceptual importance of promoting the oxidation counter-half-reaction in plasmon mediated catalysis by photorecycling in order to overcome this general limitation. A six-electron photocatalytic reaction occurs even in the absence of conventional chemical reducing agents due to the photoinduced recycling of Ag atoms from hot holes in the oxidation half-reaction. This concept of multi electron, counter-half-reaction-promoted photocatalysis provides exciting new opportunities for driving efficient light-to-energy conversion processes. PMID- 26138620 TI - Coagulation Status in Hidradenitis Suppurativa: A Danish Population- and Hospital Based Cross-Sectional Study. AB - BACKGROUND: Chronic inflammatory diseases other than hidradenitis suppurativa (HS) have been associated with prothrombotic/hypercoagulable status. OBJECTIVE: To investigate a possible association between the chronic inflammatory skin disease HS and prothrombotic/hypercoagulable state. METHODS: We performed a hospital- and population-based cross-sectional study investigating the coagulation status (thrombocytes, mean platelet volume [MPV], international normalized ratio [INR] and activated partial thromboplastin time [APTT]). RESULTS: 32 hospital HS subjects, 430 population HS subjects and 20,780 population non-HS control subjects were identified. The adjusted analyses showed no differences in the levels of thrombocytes, MPV, INR or APTT between the HS groups (hospital HS group, population HS group) when compared to controls (p = 0.089, p = 0.3078; p = 0.5499, p = 0.0659; p = 0.0932; p = 0.3432). CONCLUSION: We did not find an association between HS and prothrombotic/hypercoagulable status. Thus, thrombocytes may not be activated in HS. Furthermore, INR may not be affected in HS, suggesting that intrinsic and vitamin K-dependent coagulation factors appear unaffected. PMID- 26138621 TI - Low-temperature thermodynamics with quantum coherence. AB - Thermal operations are an operational model of non-equilibrium quantum thermodynamics. In the absence of coherence between energy levels, exact state transition conditions under thermal operations are known in terms of a mathematical relation called thermo-majorization. But incorporating coherence has turned out to be challenging, even under the relatively tractable model wherein all Gibbs state-preserving quantum channels are included. Here we find a mathematical generalization of thermal operations at low temperatures, 'cooling maps', for which we derive the necessary and sufficient state transition condition. Cooling maps that saturate recently discovered bounds on coherence transfer are realizable as thermal operations, motivating us to conjecture that all cooling maps are thermal operations. Cooling maps, though a less-conservative generalization to thermal operations, are more tractable than Gibbs-preserving operations, suggesting that cooling map-like models at general temperatures could be of use in gaining insight about thermal operations. PMID- 26138622 TI - Pharmacogenetic testing prior to carbamazepine treatment of epilepsy: patients' and physicians' preferences for testing and service delivery. AB - AIM: Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services. METHODS: Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect. RESULTS: In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI 0.19, 1.00) than not testing at 0.33 (95% CI -0.07, 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV) and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay L5.87 for a 1 percentage point increase in NPV and L3.99 for a 1 percentage point increase in PPV. CONCLUSION: The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA A*31:01 testing in routine practice. PMID- 26138623 TI - An Extraordinary Case Associated with an Allergic Reaction to Clopidogrel: Coronary Artery Spasm or Kounis Syndrome? AB - Kounis syndrome is the concurrence of acute coronary syndrome with allergic reactions, such as anaphylaxis or anaphylactoid reactions. Here, we describe a unique case: CASs (coronary artery spasms) with both non-hypersensitivity and hypersensitivity aetiology (associated with clopidogrel hypersensitivity) were observed in a 61 year-old patient. Herein, the mechanism and clinical implications of this association are discussed. PMID- 26138624 TI - Sleep: The hebbian reinforcement of the local inhibitory synapses. AB - Sleep is ubiquitous among the animal realm, and represents about 30% of our lives. Despite numerous efforts, the reason behind our need for sleep is still unknown. The Theory of neuronal Cognition (TnC) proposes that sleep is the period of time during which the local inhibitory synapses (in particular the cortical ones) are replenished. Indeed, as long as the active brain stays awake, hebbian learning guarantees that efficient inhibitory synapses lose their efficiency - just because they are efficient at avoiding the activation of the targeted neurons. Since hebbian learning is the only known mechanism of synapse modification, it follows that to replenish the inhibitory synapses' efficiency, source and targeted neurons must be activated together. This is achieved by a local depolarization that may travel (wave). The period of time during which such slow waves are experienced has been named the "slow-wave sleep" (SWS). It is cut into several pieces by shorter periods of paradoxical sleep (REM) which activity resembles that of the awake state. Indeed, SWS - because it only allows local neural activation - decreases the excitatory long distance connections strength. To avoid losing the associations built during the awake state, these long distance activations are played again during the REM sleep. REM and SWS sleeps act together to guarantee that when the subject awakes again, his inhibitory synaptic efficiency is restored and his (excitatory) long distance associations are still there. PMID- 26138626 TI - Chronic and non-healing wounds: The story of vascular endothelial growth factor. AB - The pathophysiology of the chronicity and non-healing status of wounds remains unknown. This paper presents the following hypothesis: abnormal patterns of vascular endothelial growth factor receptors (VEGFRs) are the culprits of wound chronicity and non-healing. More specifically, for patients with poor circulation, the decreased VEGFR-2 level is the cause of poor wound healing; for patients with non-compromised circulation, for example, patients with concurrent chronic wounds and active autoimmune diseases, the increased VEGFR-1 level is related to the non-healing status of wounds. The hypothesis is supported by the following facts. VEGFR-1 is the main contributor for inflammation and VEGFR-2 facilitates angiogenesis; soluble VEGFR-1 (sVEGFR-1) inactivates both VEGFR-1 and VEGFR-2. Patients with auto-immune disease have abnormally increased VEGFR-1 and decreased sVEGFR. Wounds in patients with active autoimmune diseases have poor response to electric stimulation which facilitates chronic wound healing in patients without active autoimmune diseases via increasing vascular endothelial growth factor (VEGF) secretion. Patients with chronic wounds (including diabetic foot ulcers and venous leg ulcers) but no active autoimmune diseases have decreased VEGFR-2 levels. We thus believe that abnormal patterns of VEGFRs are the culprits of wound chronicity and non-healing. For wounds with compromised circulation, VEGFR-2 decrease contributes to its chronicity; whereas for wounds with non-compromised circulation, VEGFR-1 increase is the leading cause of the non-healing status of chronic wounds. Treatments and research in wound care should be tailored to target these changes based on circulation status of wounds. Complete elucidation of changes of VEGFRs in chronic and non-healing wounds will enhance our understandings in tissue healing and thus better our selection of appropriate treatments for chronic and non-healing wounds. PMID- 26138625 TI - Relative fascicle excursion effects on dynamic strength generation during gait in children with cerebral palsy. AB - Evaluation of muscle structure gives us a better understanding of how muscles contribute to force generation which is significantly altered in children with cerebral palsy (CP). While most muscle structure parameters have shown to be significantly correlated to different expressions of strength development in children with CP and typically developing (TD) children, conflicting results are found for muscle fascicle length. Muscle fascicle length determines muscle excursion and velocity, and contrary to what might be expected, correlations of fascicle length to rate of force development have not been found for children with CP. The lack of correlation between muscle fascicle length and rate of force development in children with CP could be due, on the one hand, to the non-optimal joint position adopted for force generation on the isometric strength tests as compared to the position of TD children. On the other hand, the lack of correlation could be due to the erroneous assumption that muscle fascicle length is representative of sarcomere length. Thus, the relationship between muscle architecture parameters reflecting sarcomere length, such as relative fascicle excursions and dynamic power generation, should be assessed. Understanding of the underlying mechanisms of weakness in children with CP is key for individualized prescription and assessment of muscle-targeted interventions. Findings could imply the detection of children operating on the descending limb of the sarcomere length-tension curve, which in turn might be at greater risk of developing crouch gait. Furthermore, relative muscle fascicle excursions could be used as a predictive variable of outcomes related to crouch gait prevention treatments such as strength training. PMID- 26138627 TI - Acute hypokalemia induced by ritodrine and rebound hyperkalemia in a parturient undergoing a cesarean section. PMID- 26138628 TI - Dexmedetomidine sedation for a claustrophobic patient with obstructive sleep apnea undergoing magnetic resonance imaging. PMID- 26138629 TI - A severe interaction between Tizanidine and Ciprofloxacin. PMID- 26138630 TI - Risk factors and outcomes associated with new-onset atrial fibrillation during acute respiratory distress syndrome. AB - PURPOSE: Outcomes and risk factors associated with new-onset atrial fibrillation (AF) during acute respiratory distress syndrome (ARDS) are unclear. We investigated mortality and risk factors associated with new-onset AF during ARDS. MATERIALS AND METHODS: We obtained data from the ARDS Network Albuterol for Treatment of Acute Lung Injury trial, which prospectively identified new-onset AF among patients with ARDS as an adverse event. We determined Acute Physiology and Chronic Health Evaluation III-adjusted associations between new-onset AF and 90 day mortality. We also examined associations between new-onset AF and markers of inflammation (interleukin 6 and interleukin 8), myocardial injury (troponin I), autonomic activation (epinephrine), and atrial stretch (central venous pressure) as well as other clinical characteristics. MEASUREMENTS AND MAIN RESULTS: Of 282 patients (mean age, 51.6 years; 45% women; 77% white) enrolled in Albuterol for Treatment of Acute Lung Injury, 28 (10%) developed new-onset AF during the study. We did not identify associations between new-onset AF and baseline central venous pressure, plasma levels of troponin I, epinephrine, interleukin 6, or interleukin 8. New-onset AF during ARDS was associated with increased 90-day mortality (new onset AF, 43% vs no new-onset AF, 19%; Acute Physiology and Chronic Health Evaluation-adjusted odds ratio, 3.09 [95% confidence interval, 1.24-7.72]; P = .02). CONCLUSION: New-onset AF during ARDS is associated with increased mortality; however, its mechanisms require further study. PMID- 26138631 TI - Causes of ischemic electrocardiographic changes in near drowning: A literature review. AB - Drowning is a main cause of accidental death among children and adolescents worldwide. Ischemic electrocardiographic (ECG) changes are often encountered in victims of near drowning. We reviewed the literature for near drowning cases reporting ischemic ECG changes to study the underlying etiology for these findings. Among the 8 cases included in the analysis, ischemic ECG changes were due to takotsubo cardiomyopathy (in elderly cases especially females); coronary artery spasm (in younger cases); or hypothermia effect on ECG; and, to a lesser extent, myocardial ischemia resulting from occlusive coronary artery disease. PMID- 26138633 TI - Dual mobility cup in revision total hip arthroplasty: dislocation rate and survival after 5 years. AB - BACKGROUND: Dislocation is a common complication of total hip arthroplasty (THA), particularly when performed as revision surgery. Dual mobility cups (DMCs) minimize the risk of instability when implanted during primary THA. However, their usefulness and survival in revision THA remain unclear. We therefore conducted a retrospective study to assess DMC stability and survival at a minimal follow-up period of 5years after revision THA. HYPOTHESIS: The dislocation rate associated with DMCs for revision THA is similar to that seen after primary THA. MATERIALS AND METHODS: Cup exchange with implantation of a DMC was performed in 71 patients (74 hips) between 2000 and 2007, for the following reasons: recurrent dislocation (n=22), aseptic loosening (n=38), and infection (n=14). The DMCs were cemented in 47 cases and cementless in 27 cases. The clinical variables (Merle d'Aubigne-Postel score and Harris Hip Score) and radiological findings were collected retrospectively from the medical records and compared with those obtained at the last follow-up visit. RESULTS: Of the 74 cases, 2 were lost to follow-up. At last follow-up, the mean Merle d'Aubigne-Postel score was 15.2 (11 18) and the mean Harris Hip Score was 80.4 (51-98). Of the 8 failures, 2 (2/72, 2.7%) were related to mechanical factors (1 case each of aseptic loosening and dislocation) and 6 were changed because of infection (recurrent infection, n=4). Mechanical failure was not linked to a specific reason for revision THA. A radiolucent line was visible in 4 cases but this finding was not associated with clinical manifestations. When failure was defined as cup revision for any non infectious complication, 5-year implant survival was 99% (95% confidence interval, 93-100%). DISCUSSION: Use of a DMC in revision THA was associated with a slightly higher dislocation rate (1/72, 1.4%) than in primary THA, whereas 5 year survival was comparable. Cemented DMCs were not associated with a greater risk of loosening. CONCLUSION: DMCs are useful to decrease the risk of dislocation in revision THA performed for any reason. The low rate of loosening indicates that DMCs do not result in high stresses at the bone-implant interface. LEVEL OF EVIDENCE: IV, retrospective study. PMID- 26138634 TI - Blood-brain barrier-associated efflux transporters: a significant but underappreciated obstacle to drug development in glioblastoma. PMID- 26138635 TI - The efficacy of percutaneous AHI (arginine hydrochloride injection) for the treatment of recurrent thyroid cysts. AB - OBJECTIVES: Thyroid cysts remain a common clinical problem. Although simple aspiration, ethanol ablation, and radiofrequency ablation are effective, they have some limitations. There is therefore a need to identify a new and effective sclerosant for resolving these problems. The aim of this study was to test the efficacy as an active compound for sclerotherapy of thyroid cysts. PATIENTS AND METHODS: Eight subjects whose thyroid cysts were recurrent despite repeated simple aspiration treatments were included in this study. The cysts were aspirated and then subjected to AHI. Lack of a significant reduction in cyst size (i.e. <50%) at follow-up resulted in further AHIs. Treatment success was defined as complete disappearance or a marked (i.e.>50%) reduction in the size of the cystic portion of the thyroid nodule on follow-up ultrasonography at least 6 months after the final AHI. RESULTS: A marked size reduction of>50% was ultimately found in all of the patients (100%), with a reduction varying from 73.68% to 99.07% (P<0.029). Six of the patients received a single AHI treatment, one received two AHIs, and one received three AHIs. None of the patients suffered from a recurrence during the follow-up period. Three patients experienced tolerable pain and local tenderness. No serious side effects were reported. CONCLUSIONS: Intracystic AHI may be a safe and effective treatment for benign thyroid cysts. PMID- 26138636 TI - Measuring the impact of an interprofessional multimedia learning resource on Japanese nurses and nursing students using the Theory of Planned Behavior Medication Safety Questionnaire. AB - Interprofessional communication and teamwork are essential for medication safety; however, limited educational opportunities for health professionals and students to develop these skills exist in Japan. This study evaluated the impact of an interprofessional multimedia learning resource on registered nurses' and nursing students' intention to practice in a manner promoting medication safety. Using a quasi-experimental design, Japanese registered nurses and nursing students (n = 203) were allocated to an experimental (n = 109) or control group (n = 94). Behavioral intentions of medication safety and the predictor variables of attitudes, perceived behavioral control, and subjective norms were measured using a Japanese version of the Theory of Planned Behavior Medication Safety Questionnaire. Registered nurses in the experimental group demonstrated a greater intention to collaborate and practice in a manner that enhanced medication safety, evidenced by higher scores than the control group on all predictor variables. The results demonstrate the potential for interprofessional multimedia learning resources to positively impact the behaviors of Japanese registered nurses in relation to safe medication practices. Further research in other contexts and with other cohorts is warranted. PMID- 26138637 TI - WT1 Expression in Circulating RNA as a Minimal Residual Disease Marker for AML Patients After Stem-Cell Transplantation. AB - BACKGROUND: Circulating RNA in plasma (CRNA) refers to soluble tumor-derived ribonucleic acids (RNA). The Wilms tumor 1 (WT1) gene appears to be a highly promising marker for minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients after chemotherapy or hematopoietic stem-cell transplantation (HSCT). OBJECTIVE: This study aimed to compare the relative expression level of the WT1 gene in CRNA, bone marrow (BM)- and peripheral blood (PB)-RNA for the monitoring of MRD in AML patients after HSCT. METHODS: One hundred and eighteen AML patients were studied with WT1 expression assessed by quantitative polymerase chain reaction in plasma, BM- and PB-RNA. Correlation analysis was used to compare gene expression differences. RESULTS: The expression of the WT1 gene was successfully detected in 118 cases but was absent in controls (mean relative expression of WT1/ABL 8.77, range 0.5-56.0, P < 0.001) (WT1 in BM RNA: mean relative expression 8.66, range 0.5-56.0, P < 0.001; WT1 in PB-RNA: mean relative expression 8.55, range 0.5-54.0, P < 0.001). WT1 expression in CRNA, BM-RNA and PB-RNA showed no difference at diagnosis (CRNA vs. BM-RNA, r = 0.999; CRNA vs. PB-RNA, r = 0.988). After HSCT, 62 patients achieved remission. The expression level of WT1 in CRNA and BM-RNA in nine patients who achieved permanent remission fluctuated within the normal range (WT1/ABL < 0.02). The other 53 patients who were predicted to relapse had elevated WT1 levels in CRNA and BM-RNA. Of these 53 patients, 48 had increased expression of the WT1 gene in both CRNA and BM-RNA at a median of 1 month prior to clinical relapse. In the other five patients (5/53) diagnosed with extramedullary relapse, the level of WT1 in CRNA was elevated prior to relapse. However, in these patients WT1 expression in both BM-RNA and PB-RNA was still negative (at a median of 1 month earlier than in BM-RNA). This study indicated that CRNA was no different from BM RNA for determination of WT1 expression in AML patients (F = 0.260, P = 0.642). CONCLUSION: Analysis of WT1 expression in CRNA in AML patients could be a simple, convenient and noninvasive method to predict latent information about relapse. PMID- 26138638 TI - Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses. AB - Although DNA of bacterial and viral origin, as well as viral RNA, have been intensively studied as triggers of innate immune responses, the stimulatory properties of bacterial RNA and its role during infections have just begun to be deciphered. Bacterial RNA is a strong inducer of type I IFN and NF-kappaB dependent cytokines, and it also can activate the Nlrp3 inflammasome. In this review, we focus on the receptors and signaling pathways involved in innate immune activation by bacterial RNA and analyze the physiological relevance of bacterial RNA recognition during infections. Furthermore, we present the concept that RNA modifications can impair RNA-dependent immune activation. RNA modifications differ between eukaryotes and prokaryotes; thus, they can serve to define the innate pattern that is recognized. In this regard, we discuss the role of ribose 2'-O-methylation as a potential immune-escape mechanism. PMID- 26138639 TI - Correction: Selective Blockade of CD28-Mediated T Cell Costimulation Protects Rhesus Monkeys against Acute Fatal Experimental Autoimmune Encephalomyelitis. PMID- 26138640 TI - Social Skills Deficits in a Virtual Environment Among Spanish Children With ADHD. AB - OBJECTIVE: Research assessing the social skills of children with ADHD has predominantly relied upon North American samples. In addition, most existing work has been conducted using methodology that fails to use a controlled peer stimulus; such methods may be more vulnerable to cultural influence. METHOD: We examined the social skills of 52 Spanish children (ages 8-12) with and without ADHD using a controlled Chat Room Task, which simulates a virtual social environment where peers' responses are held constant, so that participants' social skills may be assessed. RESULTS: After statistical control of typing and reading comprehension skills, Spanish children with ADHD gave fewer prosocial comments and had greater difficulty remembering central details from the conversation between the peers, relative to comparison children. CONCLUSION: The virtual Chat Room Task may be useful to assess social skills deficits using a controlled paradigm, resulting in the identification of common social deficiencies cross-culturally. PMID- 26138641 TI - Perspectives From Masters in Rheumatology and Autoimmunity: Can We Get Closer to a Cure for Rheumatoid Arthritis? PMID- 26138642 TI - Fibroblast growth factor signaling in myofibroblasts differs from lipofibroblasts during alveolar septation in mice. AB - Pulmonary alveolar fibroblasts produce extracellular matrix in a temporally and spatially regulated pattern to yield a durable yet pliable gas-exchange surface. Proliferation ensures a sufficient complement of cells, but they must differentiate into functionally distinct subtypes: contractile myofibroblasts (MF), which generate elastin and regulate air-flow at the alveolar ducts, and, in mice and rats, lipofibroblasts (LF), which store neutral lipids. PDGF-A is required but acts in conjunction with other differentiation factors arising from adjacent epithelia or within fibroblasts. We hypothesized that FGF receptor (FGFR) expression and function vary for MF and LF and contributes to their divergent differentiation. Whereas approximately half of the FGFR3 was extracellular in MF, FGFR2 and FGFR4 were primarily intracellular. Intracellular FGFR3 localized to the multivesicular body, and its abundance may be modified by Sprouty and interaction with heat shock protein-90. FGF18 mRNA is more abundant in MF, whereas FGF10 mRNA predominated in LF, which also express FGFR1 IIIb, a receptor for FGF10. FGF18 diminished fibroblast proliferation and was chemotactic for cultured fibroblasts. Although PDGF receptor-alpha (PDGFR-alpha) primarily signals through phosphoinositide 3-kinase and Akt, p42/p44 MAP kinase (Erk1/2), a major signaling pathway for FGFRs, influenced the abundance of cell-surface PDGFR alpha. Observing different FGFR and ligand profiles in MF and LF is consistent with their divergent differentiation although both subpopulations express PDGFR alpha. These studies also emphasize the importance of particular cellular locations of FGFR3 and PDGFR-alpha, which may modify their effects during alveolar development or repair. PMID- 26138643 TI - DHA suppresses chronic apoptosis in the lung caused by perinatal inflammation. AB - We have previously shown that an adverse perinatal environment significantly alters lung growth and development and results in persistently altered cardiopulmonary physiology in adulthood. Our model of maternal LPS treatment followed by 14 days of neonatal hyperoxia exposure causes severe pulmonary disease characterized by permanent decreases in alveolarization and diffuse interstitial fibrosis. The current investigations tested the hypothesis that dysregulation of Notch signaling pathways contributes to the permanently altered lung phenotype in our model and that the improvements we have observed previously with maternal docosahexaenoic acid (DHA) supplementation are mediated through normalization of Notch-related protein expression. Results indicated that inflammation (IL-6 levels) and oxidation (F2a-isoprostanes) persisted through 8 wk of life in mice exposed to LPS/O2 perinatally. These changes were attenuated by maternal DHA supplementation. Modest but inconsistent differences were observed in Notch-pathway proteins Jagged 1, DLL 1, PEN2, and presenilin-2. We detected substantial increases in markers of apoptosis including PARP-1, APAF-1, caspase-9, BCL2, and HMGB1, and these increases were attenuated in mice that were nursed by DHA-supplemented dams during the perinatal period. Although Notch signaling is not significantly altered at 8 wk of age in mice with perinatal exposure to LPS/O2, our findings indicate that persistent apoptosis continues to occur at 8 wk of age. We speculate that ongoing apoptosis may contribute to persistently altered lung development and may further enhance susceptibility to additional pulmonary disease. Finally, we found that maternal DHA supplementation prevented sustained inflammation, oxidation, and apoptosis in our model. PMID- 26138644 TI - Neutral sphingomyelinase 2 is required for cytokine-induced skeletal muscle calpain activation. AB - Calpain contributes to infection-induced diaphragm dysfunction but the upstream mechanism(s) responsible for calpain activation are poorly understood. It is known, however, that cytokines activate neutral sphingomyelinase (nSMase) and nSMase has downstream effects with the potential to increase calpain activity. We tested the hypothesis that infection-induced skeletal muscle calpain activation is a consequence of nSMase activation. We administered cytomix (20 ng/ml TNF alpha, 50 U/ml IL-1beta, 100 U/ml IFN-gamma, 10 MUg/ml LPS) to C2C12 muscle cells to simulate the effects of infection in vitro and studied mice undergoing cecal ligation puncture (CLP) as an in vivo model of infection. In cell studies, we assessed sphingomyelinase activity, subcellular calcium levels, and calpain activity and determined the effects of inhibiting sphingomyelinase using chemical (GW4869) and genetic (siRNA to nSMase2 and nSMase3) techniques. We assessed diaphragm force and calpain activity and utilized GW4869 to inhibit sphingomyelinase in mice. Cytomix increased cytosolic and mitochondrial calcium levels in C2C12 cells (P < 0.001); addition of GW4869 blocked these increases (P < 0.001). Cytomix also activated calpain, increasing calpain activity (P < 0.02), and the calpain-mediated cleavage of procaspase 12 (P < 0.001). Procaspase 12 cleavage was attenuated by either GW4869 (P < 0.001), BAPTA-AM (P < 0.001), or siRNA to nSMase2 (P < 0.001) but was unaffected by siRNA to nSMase3. GW4869 prevented CLP-induced diaphragm calpain activation and diaphragm weakness in mice. These data suggest that nSMase2 activation is required for the development of infection-induced diaphragm calpain activation and muscle weakness. As a consequence, therapies that inhibit nSMase2 in patients may prevent infection induced skeletal muscle dysfunction. PMID- 26138645 TI - Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure. AB - Preterm infants often require supplemental oxygen due to lung immaturity, but hyperoxia can contribute to an increased risk of respiratory illness later in life. Our aim was to compare the effects of mild and moderate levels of neonatal hyperoxia on markers of pulmonary oxidative stress and inflammation and on lung architecture; both immediate and persistent effects were assessed. Neonatal mice (C57BL6/J) were raised in either room air (21% O2), mild (40% O2), or moderate (65% O2) hyperoxia from birth until postnatal day 7 (P7d). The mice were killed at either P7d (immediate effects) or lived in air until adulthood (P56d, persistent effects). We enumerated macrophages in lung tissue at P7d and immune cells in bronchoalveolar lavage fluid (BALF) at P56d. At P7d and P56d, we assessed pulmonary oxidative stress [heme oxygenase-1 (HO-1) and nitrotyrosine staining] and lung architecture. The data were interrogated for sex differences. At P7d, HO-1 gene expression was greater in the 65% O2 group than in the 21% O2 group. At P56d, the area of nitrotyrosine staining and number of immune cells were greater in the 40% O2 and 65% O2 groups relative to the 21% O2 group. Exposure to 65% O2, but not 40% O2, led to larger alveoli and lower tissue fraction in the short term and to persistently fewer bronchiolar-alveolar attachments. Exposure to 40% O2 or 65% O2 causes persistent increases in pulmonary oxidative stress and immune cells, suggesting chronic inflammation within the adult lung. Unlike 65% O2, 40% O2 does not affect lung architecture. PMID- 26138646 TI - Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs). AB - BACKGROUND: Little is known about the use of sirolimus for primary prevention of cutaneous squamous cell carcinoma (SCC) among solid organ transplant recipients (SOTRs). OBJECTIVE: We examined the association between sirolimus exposure and incident SCC risk among SOTRs within Kaiser Permanente Northern California. METHODS: Using a retrospective cohort of all Kaiser Permanente Northern California members given a diagnosis of SOTR from 2000 through 2010, we evaluated incident posttransplantation SCC risk in relation to sirolimus exposure. Sirolimus use was determined from electronic pharmacy records, and incident posttransplantation SCCs were identified from health plan electronic pathology records. We used extended Cox regression to examine the independent association between receipt of sirolimus and risk of SCC. RESULTS: Among 3539 SOTRs, 488 were exposed to sirolimus and 47 developed an incident SCC. SCC risk was not associated with ever use of sirolimus (adjusted hazard ratio 1.18, 95% confidence interval 0.84-1.16) or cumulative duration of sirolimus exposure (adjusted hazard ratio 2.75, 95% confidence interval 0.84-9.04, comparing long-term users with nonusers). LIMITATIONS: No information was available for some known SCC risk factors, such as skin type and sun exposure. CONCLUSIONS: Among a large cohort of SOTRs, sirolimus exposure was not associated with a reduction in incident posttransplantation SCC risk. PMID- 26138647 TI - Evidence-based approach to cutaneous hyperandrogenism in women. AB - Hirsutism, acne, and androgenetic alopecia are classically considered signs of cutaneous hyperandrogenism (CHA). These common skin findings have significant impacts on the quality of patients' lives and pose the diagnostic challenge of excluding underlying disorders. Many with CHA have normal serum androgen levels. Hirsutism is more strongly associated with hyperandrogenism than are acne or androgenetic alopecia. Variable association of CHA with hyperandrogenemia results from the complexity of the underlying pathophysiology, including factors local to the pilosebaceous unit. CHA often occurs in the setting of polycystic ovary syndrome, the most common disorder of hyperandrogenism, but can also present in uncommon conditions, including nonclassic adrenal hyperplasia and androgen producing tumors. A thorough history and full skin examination are important to guide appropriate diagnostic evaluation. Oral contraceptive pills with or without antiandrogens can provide therapeutic benefit for hirsutism and acne. Medical options for androgenetic alopecia remain limited. Multidisciplinary approaches may be needed given endocrine, metabolic, reproductive, and psychiatric disorders associated with CHA. More high-quality studies into the mechanisms of CHA and the benefits of antiandrogenic therapies are needed. We provide an evidence-based review of key diagnostic and therapeutic considerations in the treatment of women with CHA. PMID- 26138648 TI - [Management of cystic renal masses: Review of the literature]. AB - INTRODUCTION: The expansion of renal cysts diagnosis in the population entails to learn how to properly identify and treat potentially malignant lesions. The aim of this review article is to discuss anatomical and pathological characteristics as well as treatment of cystic renal tumors. METHOD: A literature review of Medline publications on renal cysts and cystic tumors was conducted. Prospective and retrospective studies in adults, and previous reviews were analyzed. RESULTS: Bosniak classification of renal cysts is used worldwide among urologists and radiologists to categorize cystic lesions according to their potential malignancy. There is a 0, 15, 50 and 95 % chance of cancerous cells in Bosniak I, II, III, and IV, respectively. The most frequent pathology is renal cell carcinoma, usually low grade and low stage. Category IIF cysts (F for follow-up) have a 25 % chance of malignancy and require surveillance at 6 months and regularly for 5 years. The follow-up can be done with CT imaging, MRI or contrast enhanced ultrasonography. Cyst biopsy, which was not recommended for a long time, could prevent 40 % of unnecessary surgeries for benign lesions. Bosniak category I and II cysts can be treated if symptomatic, by sclerotherapy or laparoscopic deroofing of the cyst. Category III and IV lesions must be treated as malignant tumors with security margins. CONCLUSION: Diagnosis and treatment of Bosniak category IIF renal cysts remain the primary challenge for physicians in cystic renal tumor management. Biopsies of renal cysts seem reliable, with no risk of malignant cell dissemination. PMID- 26138649 TI - Revisiting the intraperoxisomal pathway of mammalian PEX7. AB - Newly synthesized peroxisomal proteins containing a cleavable type 2 targeting signal (PTS2) are transported to the peroxisome by a cytosolic PEX5-PEX7 complex. There, the trimeric complex becomes inserted into the peroxisomal membrane docking/translocation machinery (DTM), a step that leads to the translocation of the cargo into the organelle matrix. Previous work suggests that PEX5 is retained at the DTM during all the steps occurring at the peroxisome but whether the same applies to PEX7 was unknown. By subjecting different pre-assembled trimeric PEX5 PEX7-PTS2 complexes to in vitro co-import/export assays we found that the export competence of peroxisomal PEX7 is largely determined by the PEX5 molecule that transported it to the peroxisome. This finding suggests that PEX7 is also retained at the DTM during the peroxisomal steps and implies that cargo proteins are released into the organelle matrix by DTM-embedded PEX7. The release step does not depend on PTS2 cleavage. Rather, our data suggest that insertion of the trimeric PEX5-PEX7-PTS2 protein complex into the DTM is probably accompanied by conformational alterations in PEX5 to allow release of the PTS2 protein into the organelle matrix. PMID- 26138651 TI - Concurrent Obesity, Diabetes, and Steatosis Increase Risk of Advanced Fibrosis Among HCV Patients: A Systematic Review. AB - BACKGROUND: Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease among patients with chronic hepatitis C virus infection (HCV) may contribute to more rapid disease progression. AIM: To evaluate the impact of concurrent obesity, DM, and steatosis on disease progression among HCV patients. METHODS: A systematic review using structured keyword search of MEDLINE and EMBASE from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of obesity, DM, and steatosis with advanced fibrosis (AF) among adults with chronic HCV. Studies involving HCV patients coinfected with human immunodeficiency virus, hepatitis B virus, hepatocellular carcinoma, or other chronic liver diseases were excluded. Quality assessment utilized Newcastle-Ottawa Scale. RESULTS: Twenty cohort studies met inclusion criteria for analyses. Obesity was associated with increased risk of AF in seven studies with effect size ranging from OR 1.08 to 7.69. However, four studies did not demonstrate a significant association between obesity and AF. The presence of advanced steatosis among HCV patients was associated with increased risk of AF in 12 studies (OR 1.80-14.3). Concurrent DM was associated with increased risk of AF in six studies (OR 2.25-9.24). Thirteen studies were good quality, and seven studies were fair quality. CONCLUSION: Concurrent DM and steatosis are associated with increased risk of AF among chronic HCV patients. The majority of studies demonstrated significant associations of obesity with AF. Targeted interventions to optimize management of obesity-related diseases among HCV patients may help mitigate HCV disease progression. PMID- 26138652 TI - Nod2-Rip2 Signaling Contributes to Intestinal Injury Induced by Muramyl Dipeptide Via Oligopeptide Transporter in Rats. AB - BACKGROUND AND AIMS: PepT1 can transport bacterial oligopeptide products and induce intestinal inflammation. Our aim was to investigate the mechanism of the small intestine injury induced by bacterial oligopeptide product muramyl dipeptide (MDP) which is transported by PepT1. METHODS: We perfused the jejunum with a solution with or without MDP, or with a solution of MDP + Gly-Gly and explored the degree of inflammation to determine the role of PepT1-Nod2 signaling pathway in small intestine mucosa. RESULTS: MDP perfusion induced inflammatory cell accumulation and intestinal damage, accompanied by an increase in mucosal Nod2 and Rip2 transcript expression. NFkappaB activity and inflammatory cytokine expression, including serum levels of TNF-alpha, IL-1beta, and IL-6, increased in the MDP group compared to the controls; these effects were reversed by perfusion of the nutritional dipeptide Gly-Gly. CONCLUSION: MDP can be transported through PepT1, causing inflammatory damage in the rat small intestine. Nod2-Rip2-NFkappaB signaling involved in the small intestinal inflammatory injury caused by MDP which is transported through PepT1. PMID- 26138653 TI - Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir. AB - INTRODUCTION: Loss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos(t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied. METHODS: We retrospectively studied the outcomes of 54 HBeAg positive CHB patients who were treated with either ETV (n = 30) or TDF (23) or both (n = 1) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment. RESULTS: Only 4 (7%) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24%) continued to have HBV DNA levels below 2000 IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69%) developed HBV DNA >2000 IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62%) remained HBeAg negative/anti-HBe positive, 12 (32%) became HBeAg positive, and 2 (5%) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse. CONCLUSIONS: Durability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy. PMID- 26138654 TI - Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis. AB - BACKGROUND AND AIMS: The prevalence of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is increasing at an alarming rate. The role of bile acids in the development and progression of NAFLD to NASH and cirrhosis is poorly understood. This study aimed to quantify the bile acid metabolome in healthy subjects and patients with non-cirrhotic NASH under fasting conditions and after a standardized meal. METHODS: Liquid chromatography tandem mass spectroscopy was used to quantify 30 serum and 16 urinary bile acids from 15 healthy volunteers and 7 patients with biopsy-confirmed NASH. Bile acid concentrations were measured at two fasting and four post-prandial time points following a high-fat meal to induce gallbladder contraction and bile acid reabsorption from the intestine. RESULTS: Patients with NASH had significantly higher total serum bile acid concentrations than healthy subjects under fasting conditions (2.2- to 2.4-fold increase in NASH; NASH 2595-3549 uM and healthy 1171-1458 uM) and at all post prandial time points (1.7- to 2.2-fold increase in NASH; NASH 4444-5898 uM and healthy 2634-2829 uM). These changes were driven by increased taurine- and glycine-conjugated primary and secondary bile acids. Patients with NASH exhibited greater variability in their fasting and post-prandial bile acid profile. CONCLUSIONS: Results indicate that patients with NASH have higher fasting and post-prandial exposure to bile acids, including the more hydrophobic and cytotoxic secondary species. Increased bile acid exposure may be involved in liver injury and the pathogenesis of NAFLD and NASH. PMID- 26138656 TI - Angiotensin II receptor antagonist olmesartan and NF-kappaB inhibitor as cytotoxic and apoptotic agents in MCF-7 human cell line. AB - OBJECTIVE: Over expression of renin-angiotensin system (RAS) and nuclear factor kappaB (NF-kappaB) have major role in many cancers. In this study, role of angiotensin II (Ag II) and NF-kappaB pathway in breast cancer cell line (MCF-7) proliferation were studied using olmesartan (as a novel Ag II antagonist) and Bay11-7082 (as NF-kappaB inhibitor). MATERIALS AND METHODS: Cells were treated with different concentrations of olmesartan and Bay11-7082.Cell proliferation was determined by 4, 5-Dimethylthiazol-2-yl, 2, 5-diphenyl tetrazolium (MTT) assay. Apoptotic cells were evaluated using PI staining of DNA fragmentation. RESULTS: Olmesartan and Bay11-7082 decreased cell viability. Combination of olmesartan with Bay11-7082 also decreased cell viability as compared with single agent treatments. Results showed that apoptosis is involved in olmesartan and Bay11 7082-induced toxicity. CONCLUSION: Olmesartan and Bay11-7082 inhibit the MCF-7 cells growth indicating RAS and NF-kappaB pathway blockade lead to cytotoxicity and apoptosis induction against tumour cells. So ARBs and NF-kappaB pathway inhibitors could be considered as anticancer drugs in future. PMID- 26138655 TI - Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS. AB - BACKGROUND AND AIMS: Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). METHODS: We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. RESULTS: Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. CONCLUSION: This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD. PMID- 26138657 TI - Anti-vascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy with polyps resembling grape clusters. AB - PURPOSE: The objective of this study was to investigate the 2-year outcomes of treatment with anti-vascular endothelial growth factor (VEGF) in patients with polypoidal choroidal vasculopathy (PCV) with polyps resembling grape clusters. METHODS: Twenty eyes in 20 patients were included. All patients initially received three consecutive anti-VEGF injections, followed by an as-needed re injection schedule. Patients were followed regularly at 1- to 3-month intervals. The primary outcome was change in best-corrected visual acuity (BCVA). RESULTS: The mean number of injections administered over the course of 24 months was 12.50 +/- 2.77 (range, 9-18). The logarithm of the minimum angle of resolution (logMAR) BCVA improved from 0.61 +/- 0.28 to 0.42 +/- 0.27 at 12 months (P = 0.015), and 0.44 +/- 0.31 at 24 months (P = 0.056). At 24 months, BCVA had improved in 6 (30.0 %) eyes by 0.3 logMAR or more, was stable in 11 (55.0 %) eyes, and had decreased in 3 (15.0 %) eyes. Complete absorption of fluid was achieved with anti VEGF treatment in 18 (90 %) eyes at least once during the 2-year follow-up period, and 10 (50 %) eyes revealed a dry macula at 24 months. Two eyes (10.0 %) received rescue photodynamic therapy because subfoveal fluid persisted despite six and seven consecutive anti-VEGF injections. Of 18 eyes treated only with anti VEGF agents, 3 (16.7 %) revealed partial resolution of the polypoidal lesions at 24 months. CONCLUSIONS: A treatment regimen with anti-VEGF effectively improved or maintained visual acuity over a 24-month period in patients with PCV with clusters of grape-like polyps, and required frequent injections, comparable to typical choroidal neovascularization in age-related macular degeneration. PMID- 26138658 TI - APIC offers virtual education on effective use of data with EPI(r) Analytics Learning Lab. PMID- 26138659 TI - Variation in health care worker removal of personal protective equipment. AB - In the current era of emerging pathogens such as Ebola virus, removal of personal protective equipment (PPE) is crucial to reduce contamination of health care workers. However, current removal practices are not well described. We undertook a systematic evaluation of health care worker removal of PPE for contact isolation to examine variation in removal procedures. Findings indicate that under usual conditions, only about half of health care workers correctly remove their PPE, and very few remove their PPE in the correct order and dispose of it in the proper location. PMID- 26138660 TI - Effect of perioperative mupirocin and antiseptic body wash on infection rate and causative pathogens in patients undergoing cardiac surgery. AB - INTRODUCTION: Preoperative nasal mupirocin has been shown to reduce surgical site infections (SSIs) in patients undergoing cardiac surgery. We analyzed the effect of mupirocin plus antiseptic body wash on SSI rate and etiology. METHODS: Prospective SSI surveillance was done for patients undergoing cardiac surgery before and after implementation of mupirocin nasal ointment and chlorhexidine/octenidine body wash. RESULTS: Overall SSI rate was 8.6% (81 out of 945) for the control and 6.9% (58 out of 842) for the intervention cohort (P = .19). In multivariable analysis, the study protocol was associated with an odds ratio of 0.61 (95% confidence interval, 0.41-0.91; P = .015) with regard to any SSI. This effect was exclusively due to a reduction in superficial SSIs and was observed both in patients with preoperative and postoperative treatment initiation. Coagulase-negative staphylococci (CoNS), the most commonly isolated pathogen, were found in 37% and 48% (P = .19) of patients in the control and the intervention cohort, respectively. CoNS were methicillin resistant in 69% of cases. CONCLUSIONS: Mupirocin and antiseptic body wash reduced the rate of superficial but not deep or organ/space SSIs. Postoperative patient treatment may be critical in reducing the risk for superficial SSI, presumably due to a reduction of bacterial skin load. A high proportion of SSI was due to methicillin resistant CoNS and thus not covered by routine perioperative antimicrobial prophylaxis. PMID- 26138662 TI - Peripheral Perfusion Index Predicts Hypotension during Fluid Withdrawal by Continuous Veno-Venous Hemofiltration in Critically Ill Patients. AB - AIM: Peripheral perfusion may predict harmful hypovolemic hypotension during fluid withdrawal by continuous veno-venous hemofiltration (CVVH) in critically ill patients with acute kidney injury. METHODS: Twenty-three critically ill AKI patients were subjected to progressive fluid withdrawal. Systemic hemodynamics and peripheral perfusion index (PPI) by pulse oximetry, forearm-to-fingertip skin temperature gradient (Tskin-diff) and tissue oxygen saturation (StO2, near infra red spectroscopy) were measured. RESULTS: Most hemodynamic values decreased with fluid withdrawal, particularly in the hypotensive group, except for stroke volume (SV) and cardiac output, which decreased to a great extent in the non-hypotensive patients. Increases in systemic vascular resistance (SVR) were less in hypotension. Baseline pulse pressure and PPI were lower in hypotensive (n = 10) than non-hypotensive patients and subsequent PPI values paralleled SV decreases. A baseline PPI <=0.82 AU predicted hypotension with a sensitivity of 70%, and a specificity of 92% (AUC 0.80 +/- 0.11, p = 0.004). CONCLUSION: Progressive fluid withdrawal during CVVH is poorly tolerated in patients with less increases in SVR. The occurrence of hypotension can be predicted by low baseline PPI. PMID- 26138663 TI - Shape effect of Ag-Ni binary nanoparticles on catalytic hydrogenation aided by surface plasmons. AB - Ag-Ni binary nanoparticles with different shapes (snowman and core-shell) were synthesized by modulating the lattice strain. In the catalytic hydrogenation of 4 nitrophenol, a significant enhancement of the reaction rate was observed for the snowman shape in comparison with the core-shell shape under light irradiation. PMID- 26138664 TI - Genome-wide association mapping of time-dependent growth responses to moderate drought stress in Arabidopsis. AB - Large areas of arable land are often confronted with irregular rainfall resulting in limited water availability for part(s) of the growing seasons, which demands research for drought tolerance of plants. Natural variation was observed for biomass accumulation upon controlled moderate drought stress in 324 natural accessions of Arabidopsis. Improved performance under drought stress was correlated with early flowering and lack of vernalization requirement, indicating overlap in the regulatory networks of flowering time and drought response or correlated responses of these traits to natural selection. In addition, plant size was negatively correlated with relative water content (RWC) independent of the absolute water content (WC), indicating a prominent role for soluble compounds. Growth in control and drought conditions was determined over time and was modelled by an exponential function. Genome-wide association (GWA) mapping of temporal plant size data and of model parameters resulted in the detection of six time-dependent quantitative trait loci (QTLs) strongly associated with drought. Most QTLs would not have been identified if plant size was determined at a single time point. Analysis of earlier reported gene expression changes upon drought enabled us to identify for each QTL the most likely candidates. PMID- 26138665 TI - High-resolution quantitative determination of dielectric function by using scattering scanning near-field optical microscopy. AB - A new method for high-resolution quantitative measurement of the dielectric function by using scattering scanning near-field optical microscopy (s-SNOM) is presented. The method is based on a calibration procedure that uses the s-SNOM oscillating dipole model of the probe-sample interaction and quantitative s-SNOM measurements. The nanoscale capabilities of the method have the potential to enable novel applications in various fields such as nano-electronics, nano photonics, biology or medicine. PMID- 26138666 TI - Quantification of Ponceau 4R in Foods by Indirect Competitive Enzyme-Linked Immunosorbent Assay (icELISA). AB - As one of the rarely allowable azo dyes, ponceau 4R can be added in some foods in some countries. However, it is necessary to develop a credible and rapid analytical method for its monitoring, because of its potentially harmful risk. The hapten of ponceau 4R was first designed and synthesized by introducing a primary amine group into the structure of ponceau 4R. Based on the well-prepared hapten, the immunogen of ponceau 4R was prepared using glutaraldehyde to link ponceau 4R to the carrier protein. The triggered polyclonal antibody was obtained and tested by ELISA to optimize the proper dilution. An icELISA was developed for ponceau 4R, and the IC50 of the method is 36.82 ng/mL. The limit of detection is 0.80 ng/mL, and the linear range is 1-10000 ng/mL. Five selected structural analogues have no cross-reactivity with the anti-ponceau 4R polyclonal antibody (<0.3). In three food samples (grape juice, carbonated beverage, and RIO cocktail), the assay exhibits good stability and reproducibility with a recovery range of 93.87-103.77%, and the intra- and interassay coefficients of variation were <11.73%. The results indicate that the proposed icELISA is sensitive, accurate, specific, and simple, which provides an alternative for the detection of ponceau 4R in foods. PMID- 26138667 TI - Litomosoides sigmodontis induces TGF-beta receptor responsive, IL-10-producing T cells that suppress bystander T-cell proliferation in mice. AB - Helminth parasites suppress immune responses to prolong their survival within the mammalian host. Thereby not only helminth-specific but also nonhelminth-specific bystander immune responses are suppressed. Here, we use the murine model of Litomosoides sigmodontis infection to elucidate the underlying mechanisms leading to this bystander T-cell suppression. When OT-II T cells specific for the third party antigen ovalbumin are transferred into helminth-infected mice, these cells respond to antigen-specific stimulation with reduced proliferation compared to activation within non-infected mice. Thus, the presence of parasitic worms in the thoracic cavity translates to suppression of T cells with a different specificity at a different site. By eliminating regulatory receptors, cytokines, and cell populations from this system, we provide evidence for a two-staged process. Parasite products first engage the TGF-beta receptor on host-derived T cells that are central to suppression. In a second step, host-derived T cells produce IL-10 and subsequently suppress the adoptively transferred OT-II T cells. Terminal suppression was IL-10-dependant but independent of intrinsic TGF-beta receptor- or PD-1-mediated signaling in the suppressed OT-II T cells. Blockade of the same key suppression mediators, i.e. TGF-beta- and IL-10 receptor, also ameliorated the suppression of IgG response to bystander antigen vaccination in L. sigmodontis-infected mice. PMID- 26138668 TI - Discourses of aggression in forensic mental health: a critical discourse analysis of mental health nursing staff records. AB - Managing aggression in mental health hospitals is an important and challenging task for clinical nursing staff. A majority of studies focus on the perspective of clinicians, and research mainly depicts aggression by referring to patient related factors. This qualitative study investigates how aggression is communicated in forensic mental health nursing records. The aim of the study was to gain insight into the discursive practices used by forensic mental health nursing staff when they record observed aggressive incidents. Textual accounts were extracted from the Staff Observation Aggression Scale-Revised (SOAS-R), and Fairclough's critical discourse analysis was used to identify short narrative entries depicting patients and staffs in typical ways. The narratives contained descriptions of complex interactions between patient and staff that were linked to specific circumstances surrounding the patient. These antecedents, combined with the aggression incident itself, created stereotyping representations of forensic psychiatric patients as deviant, unpredictable and dangerous. Patient and staff identities were continually (re)produced by an automatic response from the staff that was solely focused on the patient's behavior. Such response might impede implementation of new strategies for managing aggression. PMID- 26138670 TI - Atomic and molecular analysis highlights the biophysics of unprotonated and protonated retinal in UV and scotopic vision. AB - During the photoreaction of rhodopsin, retinal isomerizes, rotating the C11[double bond, length as m-dash]C12 pi-bond from cis to an all-trans configuration. Unprotonated (UR) or protonated (PR) retinal in the Schiff's base (SB) is related to UV and light vision. Because the UR and PR have important differences in their physicochemical reactivities, we compared the atomic and molecular properties of these molecules using DFT calculations. The C10 C11[double bond, length as m-dash]C12-C13 dihedral angle was rotated from 0 degrees to 180 degrees in 45 degrees steps, giving five conformers, and the following were calculated from them: atomic orbital (AO) contributions to the HOMO and LUMO, atomic charges, bond length, bond order, HOMO, LUMO, hardness, electronegativity, polarizability, electrostatic potential, UV-vis spectra and dipole moment (DM). Similarly, the following were analyzed: the energy profile, hybridization, pyramidalization and the hydrogen-out-of-plane (HOOP) wagging from the H11-C11[double bond, length as m-dash]C12-H12 dihedral angle. In addition, retinal with a water H-bond (HR) in the SB was included for comparison. Interestingly, in the PR, C11 and C12 are totally the LUMO and the HOMO, respectively, and have a large electronegativity difference, which predicts an electron jump in these atoms during photoexcitation. At the same time, the PR showed a longer bond length and lower bond order, with a larger DM, lower HOMO LUMO gap, lower hardness and higher electronegativity. In addition, the AOs of 45 degrees and -90 degrees conformers changed significantly, from pz to py, during the rotation concomitantly with marked hybridization, smooth pyramidalization and lower HOOP activity. Clearly, the atomic and molecular differences between the UR and PR are overwhelming, including the rotational energy profile and light absorption spectra, which indicates that light absorption of UR and PR is already determined by the retinal characteristics of the SB protonation. The HR-model compared with UR shows a lower energy barrier and a discreet bathochromic effect in the UV region. PMID- 26138669 TI - Histological Quantification of Gene Silencing by Intratracheal Administration of Dry Powdered Small-Interfering RNA/Chitosan Complexes in the Murine Lung. AB - PURPOSE: The use of small-interfering RNA (siRNA) as an inhalation therapy has recently received much attention. Some reports have confirmed the suppression of gene expression in whole lungs following intratracheal administration of dry powdered siRNA; however, the anatomical location in the lung where gene silencing occurs has not been precisely identified. Here, we aimed to histologically evaluate gene silencing efficacy in murine lungs by intratracheal administration of an siRNA/chitosan complex as a dry powder. METHODS: Enhanced green fluorescence protein (EGFP)-specific siRNA (EGFP-siRNA)/chitosan powder was prepared and administered intratracheally to EGFP transgenic mice or mice carrying metastatic lung tumors consisting of Lewis lung carcinoma (LLC) cells stably expressing EGFP (EGFP-LLCs). Thereafter, green fluorescence intensities were quantified in the airways, parenchyma, and lung tumors. RESULTS: Intratracheal administration of the EGFP-siRNA/chitosan powder suppressed EGFP expression in the bronchi, bronchioles, and alveolar walls of EGFP transgenic mice. Additionally, EGFP-siRNA/chitosan effectively silenced EGFP expression in lung tumors consisting of EGFP-LLC cells. CONCLUSIONS: Pulmonary administration of siRNA/chitosan powder suppressed gene expression throughout the lung and in lung tumors. Therefore, this may become a powerful strategy to target genes expressed in a wide range of respiratory diseases involving the airways, parenchyma, and lung tumors. PMID- 26138671 TI - Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity. AB - Selected cytotoxic chemicals can provoke the immune system to recognize and destroy malignant tumors. Most of the studies on immunogenic cell death are focused on the signals that operate on a series of receptors expressed by dendritic cells to induce tumor antigen-specific T-cell responses. Here, we explored the effects of oxaliplatin, an immunogenic cell death inducer, on the induction of stress ligands and promotion of natural killer (NK) cell-mediated cytotoxicity in human ovarian cancer cells. The results indicated that treatment of tumor cells with oxaliplatin induced the production of type I interferons and chemokines and enhanced the expression of major histocompatibility complex class I-related chains (MIC) A/B, UL16-binding protein (ULBP)-3, CD155 and TNF-related apoptosis-inducing ligand (TRAIL)-R1/R2. Furthermore, oxaliplatin but not cisplatin treatment enhanced susceptibility of ovarian cancer cells to NK cell mediated cytolysis. In addition, activated NK cells completely abrogated the growth of cancer cells that were pretreated with oxaliplatin. However, cancer cells pretreated with the same concentration of oxaliplatin alone were capable of potentiating regrowth over a period of time. These results suggest an advantage in combining oxaliplatin and NK cell-based therapy in the treatment of ovarian cancer. Further investigation on such potential combination therapy is warranted. PMID- 26138672 TI - The relationship between manual coordination and mental health. AB - Motor coordination impairments frequently co-occur with other developmental disorders and mental health problems in clinically referred populations. But does this reflect a broader dimensional relationship within the general population? A clearer understanding of this relationship might inform improvements in mental health service provision. However, ascertainment and referral bias means that there is limited value in conducting further research with clinically referred samples. We, therefore, conducted a cross-sectional population-based study investigating children's manual coordination using an objective computerised test. These measures were related to teacher-completed responses on a behavioural screening questionnaire [the Strength and Difficulties Questionnaire (SDQ)]. We sampled 298 children (4-11 years old; 136 males) recruited from the general population. Hierarchical (logistic and linear) regression modelling indicated significant categorical and continuous relationships between manual coordination and overall SDQ score (a dimensional measure of psychopathology). Even after controlling for gender and age, manual coordination explained 15 % of the variance in total SDQ score. This dropped to 9 % after exclusion of participants whose SDQ responses indicated potential mental health problems. These results: (1) indicate that there is a clear relationship between children's motor and mental health development in community-based samples; (2) demonstrate the relationship's dimensional nature; and (3) have implications for service provision. PMID- 26138673 TI - Evolution of Courtship Songs in Xenopus : Vocal Pattern Generation and Sound Production. AB - The extant species of African clawed frogs (Xenopus and Silurana) provide an opportunity to link the evolution of vocal characters to changes in the responsible cellular and molecular mechanisms. In this review, we integrate several robust lines of research: evolutionary trajectories of Xenopus vocalizations, cellular and circuit-level mechanisms of vocalization in selected Xenopus model species, and Xenopus evolutionary history and speciation mechanisms. Integrating recent findings allows us to generate and test specific hypotheses about the evolution of Xenopus vocal circuits. We propose that reduced vocal sex differences in some Xenopus species result from species-specific losses of sexually differentiated neural and neuromuscular features. Modification of sex hormone-regulated developmental mechanisms is a strong candidate mechanism for reduced vocal sex differences. PMID- 26138674 TI - Dementia care mapping: effects on residents' quality of life and challenging behavior in German nursing homes. A quasi-experimental trial. AB - BACKGROUND: Person-centered care (PCC) is a widely recognized concept in dementia research and care. Dementia Care Mapping (DCM) is a method for implementing PCC. Prior studies have yielded heterogeneous results regarding the effectiveness of DCM for people with dementia (PwD). We aimed to investigate the effectiveness of DCM with regard to quality of life (QoL) and challenging behavior in PwD in nursing homes (NHs). METHODS: Leben-QD II is an 18-month, three-armed, pragmatic quasi-experimental trial. The sample of PwD was divided into three groups with three living units per group: (A) DCM applied since 2009, (B) DCM newly introduced during the study, and (C) a control intervention based on a regular and standardized QoL rating. The primary outcome was QoL measured with the Quality of Life-Alzheimer's Disease (QoL-AD) proxy, and the secondary outcomes were QoL (measured with QUALIDEM) and challenging behavior (measured with the Neuropsychiatric Inventory Nursing Home version, NPI-NH). RESULTS: There were no significant differences either between the DCM intervention groups and the control group or between the two DCM intervention groups regarding changes in the primary or secondary outcomes. At baseline, the estimated least square means of the QoL-AD proxy for groups A, B, and C were 32.54 (confidence interval, hereafter CI: 29.36-35.72), 33.62 (CI: 30.55-36.68), and 30.50 (CI: 27.47-33.52), respectively. The DCM groups A (31.32; CI: 28.15-34.48) and B (27.60; CI: 24.51 30.69) exhibited a reduction in QoL values, whereas group C exhibited an increase (32.54; CI: 29.44-35.64) after T2. CONCLUSIONS: DCM exhibited no statistically significant effect in terms of QoL and challenging behavior of PwD in NHs. To increase the likelihood of a positive effect for PwD, it is necessary to ensure successful implementation of the intervention. PMID- 26138675 TI - Critical role for Orai1 C-terminal domain and TM4 in CRAC channel gating. AB - Calcium flux through store-operated calcium entry is a major regulator of intracellular calcium homeostasis and various calcium signaling pathways. Two key components of the store-operated calcium release-activated calcium channel are the Ca(2+)-sensing protein stromal interaction molecule 1 (STIM1) and the channel pore-forming protein Orai1. Following calcium depletion from the endoplasmic reticulum, STIM1 undergoes conformational changes that unmask an Orai1-activating domain called CAD. CAD binds to two sites in Orai1, one in the N terminal and one in the C terminal. Most previous studies suggested that gating is initiated by STIM1 binding at the Orai1 N-terminal site, just proximal to the TM1 pore-lining segment, and that binding at the C terminal simply anchors STIM1 within reach of the N terminal. However, a recent study had challenged this view and suggested that the Orai1 C-terminal region is more than a simple STIM1-anchoring site. In this study, we establish that the Orai1 C-terminal domain plays a direct role in gating. We identify a linker region between TM4 and the C-terminal STIM1-binding segment of Orai1 as a key determinant that couples STIM1 binding to gating. We further find that Proline 245 in TM4 of Orai1 is essential for stabilizing the closed state of the channel. Taken together with previous studies, our results suggest a dual-trigger mechanism of Orai1 activation in which binding of STIM1 at the N- and C-terminal domains of Orai1 induces rearrangements in proximal membrane segments to open the channel. PMID- 26138677 TI - Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. PMID- 26138676 TI - Mutation of kri1l causes definitive hematopoiesis failure via PERK-dependent excessive autophagy induction. AB - Dysregulation of ribosome biogenesis causes human diseases, such as Diamond Blackfan anemia, del (5q-) syndrome and bone marrow failure. However, the mechanisms of blood disorders in these diseases remain elusive. Through genetic mapping, molecular cloning and mechanism characterization of the zebrafish mutant cas002, we reveal a novel connection between ribosomal dysfunction and excessive autophagy in the regulation of hematopoietic stem/progenitor cells (HSPCs). cas002 carries a recessive lethal mutation in kri1l gene that encodes an essential component of rRNA small subunit processome. We show that Kri1l is required for normal ribosome biogenesis, expansion of definitive HSPCs and subsequent lineage differentiation. Through live imaging and biochemical studies, we find that loss of Kri1l causes the accumulation of misfolded proteins and excessive PERK activation-dependent autophagy in HSPCs. Blocking autophagy but not inhibiting apoptosis by Bcl2 overexpression can fully rescue hematopoietic defects, but not the lethality of kri1l(cas002) embryos. Treatment with autophagy inhibitors (3-MA and Baf A1) or PERK inhibitor (GSK2656157), or knockdown of beclin1 or perk can markedly restore HSPC proliferation and definitive hematopoietic cell differentiation. These results may provide leads for effective therapeutics that benefit patients with anemia or bone marrow failure caused by ribosome disorders. PMID- 26138678 TI - The calcium-sensing receptor and integrins modulate cerebellar granule cell precursor differentiation and migration. AB - In the developing cerebellum granule cell precursors (GCPs) proliferate in the external granule cell layer before differentiating and migrating to the inner granule cell layer. Aberrant GCP proliferation leads to medulloblastoma, the most prevalent form of childhood brain cancer. Here, we demonstrate that the calcium sensing receptor (CaSR), a homodimeric G-protein coupled receptor, functions in conjunction with cell adhesion proteins, the integrins, to enhance GCP migration and cell homing by promoting GCP differentiation. During the second postnatal week a robust peak in CaSR expression was observed in GCPs; reciprocal immunoprecipitation experiments conducted during this period established that the CaSR and beta1 integrins are present together in a macromolecular protein complex. Analysis of cell-surface proteins demonstrated that activation of the CaSR by positive allosteric modulators promoted plasma membrane expression of beta1 integrins via ERK2 and AKT phosphorylation and resulted in increased GCP migration toward an extracellular matrix protein. The results of in vivo experiments whereby CaSR modulators were injected i.c.v. revealed that CaSR activation promoted radial migration of GCPs by enhancing GCP differentiation, and conversely, a CaSR inhibitor disrupted GCP differentiation and promoted GCP proliferation. Our results demonstrate that an ion-sensing G-protein coupled receptor acts to promote neuronal differentiation and homing during cerebellar maturation. These findings together with those of others also suggest that CaSR/integrin complexes act to transduce extracellular calcium signals into cellular movement, and may function in this capacity as a universal cell migration/homing complex in the developing brain. PMID- 26138679 TI - Prenatal ultrasound and Doppler findings of progressing portal hypertension in a fetus with congenital cystic hepatobiliary disease. PMID- 26138680 TI - Benzocaine loaded solid lipid nanoparticles: Formulation design, in vitro and in vivo evaluation of local anesthetic effect. AB - The aim of the present work is the development and evaluation of solid lipid nanoparticles (SLNs) as carrier system for topical delivery of benzocaine (BZC) improving its local anesthesia aiming to produce a fast acting and long lasting topical formulation. BZC loaded SLNs were prepared using a full factorial design to study the influence of the type of polyoxyethylene sorbitan ester surfactants as well as their concentration as independent variables on the particle size, entrapment efficacy and zeta potential selected as dependent variables. Design of experiment (DOE) and the analysis of variance (ANOVA) were conducted to assess the optimization of the developed formulations. The results indicated that the fatty acid chain length of tested surfactants and their concentration had a significant effect on the studied responses. The optimized formulations were spherical in shape of mean particle diameters<350 nm with negatively charged surface <-20mV. Particles were characterized using differential scanning calorimetry and X-ray powder diffraction confirming the amorphous nature and the uniformity of drug inclusion in the lipid matrix. Optimized BZC-SLNs were incorporated into hydrogels characterized by a pseudoplastic non-Newtonian behavior. In vitro release study revealed an apparently biphasic release process with sustained release profile following Higuchi kinetics. BZC loaded SLNs hydrogels showed more potent anesthetic effect compared to BZC hydrogel evaluated using tail-flick analgesimeter, confirming significant improvement in both the intensity and duration of anesthetic effect. The above results proved that SLNs represent good candidates to encapsulate BZC improving its therapeutic efficacy for the topical treatment of pain. PMID- 26138681 TI - In vivo Near-infrared Fluorescence Tumor Imaging Using DiR-loaded Nanocarriers. AB - The hydrophobic long-chain dialkylcarbocyanine 1,1'-dioctadecyl-3,3,3',3' tetramethylindotricarbocyanine iodide (DiR) is an important near infrared (NIR) fluorescent dye, which has a satisfactory photo stability for continuous excitation. During the past decade, it has been widely used for in vivo monitoring of cells. With the fast emergence of novel tumor-targeted nanocarriers, the applications of DiR in the development of fluorescent or multifunctional nano-probes for in vivo tumor imaging are also reported. In these studies, DiR-loaded nanocarriers have resulted in good fluorescence images, indicating the great potential of this dye. However, some important issues about DiR-loaded nanocarriers were often overlooked. These issues include the in vivo fluorescent properties, stability, toxicity, retention and metabolization of DiR loaded nanocarriers. This review introduced the current use and the properties of DiR-loaded nanocarriers for in vivo tumor imaging. The perspective outlook at the last section highlights the future application of DiR-loaded nanocarriers. PMID- 26138682 TI - Toward the stereochemical identification of prohibited characterizing flavors in tobacco products: the case of strawberry flavor. AB - With the revision of the European Tobacco Products Directive (2014/40/EU), characterizing flavors such as strawberry, candy, vanillin or chocolate will be prohibited in cigarettes and fine-cut tobacco. Product surveillance will therefore require analytical means to define and subsequently detect selected characterizing flavors that are formed by supplemented flavors within the complex matrix tobacco. We have analyzed strawberry-flavored tobacco products as an example for characterizing fruit-like aroma. Using this approach, we looked into aroma components to find indicative patterns or features that can be used to satisfy obligatory product information as requested by the European Directive. Accordingly, a headspace solid-phase microextraction (HS-SPME) technique was developed and coupled to subsequent gas chromatography-mass spectrometry (GC/MS) to characterize different strawberry-flavored tobacco products (cigarettes, fine cut tobacco, liquids for electronic cigarettes, snus, shisha tobacco) for their volatile additives. The results were compared with non-flavored, blend characteristic flavored and other fruity-flavored cigarettes, as well as fresh and dried strawberries. Besides different esters and aldehydes, the terpenes linalool, alpha-terpineol, nerolidol and limonene as well as the lactones gamma decalactone, gamma-dodecalactone and gamma-undecalactone could be verified as compounds sufficient to convey some sort of strawberry flavor to tobacco. Selected flavors, i.e., limonene, linalool, alpha-terpineol, citronellol, carvone and gamma-decalactone, were analyzed further with respect to their stereoisomeric composition by using enantioselective HS-SPME-GC/MS. These experiments confirmed that individual enantiomers that differ in taste or physiological properties can be distinguished within the tobacco matrix. By comparing the enantiomeric composition of these compounds in the tobacco with that of fresh and dried strawberries, it can be concluded that non-natural strawberry aroma is usually used to produce strawberry-flavored tobacco products. Such authenticity control can become of interest particularly when manufacturers claim that natural sources were used for flavoring of products. Although the definition of characterizing flavors by analytical means remains challenging, specific compounds or features are required to be defined for routine screening of reported information. Clarifications by sensory testing might still be necessary, but could be limited to a few preselected samples. PMID- 26138683 TI - Toxic effects of HT-2 toxin on mouse oocytes and its possible mechanisms. AB - T-2 toxin is one of the type A trichothecene mycotoxins that is considered to be the most toxic of the trichothecenes. T-2 toxin has been shown to exert various toxic effects in farm animals and humans, as it induces lesions in the brain and in lymphoid, hematopoietic, and gastrointestinal tissues. HT-2 toxin is the major metabolite of T-2 toxin. There is little information regarding the effects of HT 2 toxin on the female reproductive system, particularly oocyte maturation. Thus, in this study, we investigated the toxic effects of HT-2 on mouse oocyte maturation and its possible mechanisms of action. HT-2 toxin exposure disrupted oocyte maturation, reduced actin expression in both the oocyte cortex and cytoplasm, and disrupted meiotic spindle morphology by reducing p-MAPK protein level. HT-2 toxin exposure also induced oxidative stress and resulted in oocyte apoptosis, as shown by ROS accumulation, increased SOD mRNA level, and the expression of the early apoptosis marker Annexin V and increased caspase-3 and bax mRNA levels. Additionally, HT-2 toxin exposure increased LC3 and ATG12 protein levels and lc3 and atg14 mRNA levels, which indicated that HT-2 toxin induced autophagy in mouse oocytes. We also examined for possible epigenetic modifications. Fluorescence intensity analysis showed that 5mC level increased after HT-2 toxin exposure, whereas H3K9me2 and H3K27me3 levels decreased after HT 2 toxin exposure, which indicated that DNA and histone methylations were altered. Thus, our results indicated that HT-2 toxin exposure reduced mouse oocyte maturation capability by affecting cytoskeletal dynamics, apoptosis/autophagy, oxidative stress, and epigenetic modifications. PMID- 26138684 TI - European Tobacco Product Directive: How to address characterizing flavors as a matter of attractiveness? PMID- 26138685 TI - The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy. AB - Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide specific, preexisting CD8(+) T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell-based immunotherapy of MM. PMID- 26138686 TI - MicroRNA-17-92 controls T-cell responses in graft-versus-host disease and leukemia relapse in mice. AB - MicroRNAs (miRs) play important roles in orchestrating many aspects of the immune response. The miR-17-92 cluster, which encodes 6 miRs including 17, 18a, 19a, 20a, 19b-1, and 92-1, is among the best characterized of these miRs. The miR-17 92 cluster has been shown to regulate a variety of immune responses including infection, tumor, and autoimmunity, but the role of this cluster in T-cell response to alloantigens has not been previously explored. By using major histocompatibility complex (MHC)-matched, -mismatched, and haploidentical murine models of allogeneic bone marrow transplantation (allo-BMT), we demonstrate that the expression of miR-17-92 on donor T cells is essential for the induction of graft-versus-host disease (GVHD), but dispensable for the graft-versus-leukemia (GVL) effect. The miR-17-92 plays a major role in promoting CD4 T-cell activation, proliferation, survival, and Th1 differentiation, while inhibiting Th2 and iTreg differentiation. Alternatively, miR-17-92 may promote migration of CD8 T cells to GVHD target organs, but has minimal impact on CD8 T-cell proliferation, survival, or cytolytic function, which could contribute to the preserved GVL effect mediated by T cells deficient for miR-17-92. Furthermore, we evaluated a translational approach and found that systemic administration of antagomir to block miR-17 or miR-19b in this cluster significantly inhibited alloreactive T-cell expansion and interferon-gamma (IFNgamma) production, and prolonged the survival in recipients afflicted with GVHD while preserving the GVL effect. Taken together, the current work provides a strong rationale and demonstrates the feasibility to target miR-17-92 for the control of GVHD while preserving GVL activity after allo-BMT. PMID- 26138687 TI - Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP. AB - Immune thrombocytopenia (ITP) patients with similarly low platelet counts differ in their tendency to bleed. To determine if differences in platelet function in ITP patients account for this variation in bleeding tendency, we conducted a single-center, cross-sectional study of pediatric patients with ITP. Bleeding severity (assessed by standardized bleeding score) and platelet function (assessed by whole blood flow cytometry) with and without agonist stimulation was evaluated in 57 ITP patients (median age, 9.9 years). After adjustment for platelet count, higher levels of thrombin receptor activating peptide (TRAP) stimulated percent P-selectin- and activated glycoprotein (GP)IIb-IIIa-positive platelets were significantly associated with a lower bleeding score, whereas higher levels of immature platelet fraction (IPF), TRAP-stimulated platelet surface CD42b, unstimulated platelet surface P-selectin, and platelet forward light scatter (FSC) were associated with a higher bleeding score. Thus, platelet function tests related to platelet age (IPF, FSC) and activation through the protease activated receptor 1 (PAR1) thrombin receptor (TRAP-stimulated P selectin, activated GPIIb-IIIa, and CD42b), independent of platelet count, are associated with concurrent bleeding severity in ITP. These tests may be useful markers of future bleeding risk in ITP. PMID- 26138688 TI - Percutaneous Peritoneal Dialysis Catheter Placement in Patients with Complex Abdomen. AB - Peritoneal dialysis (PD) is an effective treatment for end-stage renal disease. There are several techniques of percutaneous PD catheter placement including trocar or Seldinger techniques. Placement can be performed with fluoroscopy and/or sonography or as a blind percutaneous procedure. Historically, percutaneous PD catheters have been placed in patients even if they had prior abdominal surgeries. The outcomes of percutaneous PD catheter placement in patients with complex abdomen (patients with two or more abdominal surgeries or known adhesions) are unknown. This study was carried out to determine the outcomes of percutaneous PD catheter placements using Seldinger technique with sonography and fluoroscopy in patients with complex abdomen. Preprocedure sonography was also used to identify site of adhesions and blood vessels. The goal was to see if ultrasound and fluoroscopy would support placement of PD catheters in patients with complex abdomens. There were total of 10 catheter placements in 10 patients with complex abdomen. The initial success rate was 100%. The patients had an average of 2.8 abdominal surgeries. The mean BMI was 28.4. There were no incidences of perforation or failed placements. One catheter was replaced due to outflow failure and one patient discontinued PD due to peri catheter leak. One year catheter survival was 80%. Our study demonstrates benefits of using ultrasonography and fluoroscopy during percutaneous PD catheter placement by the Seldinger technique in patients with complex abdomen. PMID- 26138689 TI - NMR assignment of intrinsically disordered self-processing module of the FrpC protein of Neisseria meningitidis. AB - The self-processing module (SPM) is an internal segment of the FrpC protein (P415 F591) secreted by the pathogenic Gram-negative bacterium Neisseria meningitidis during meningococcal infection of human upper respiratory tract. SPM mediates 'protein trans-splicing', a unique natural mechanism for editing of proteins, which involves a calcium-dependent autocatalytic cleavage of the peptide bond between D414 and P415 and covalent linkage of the cleaved fragment through its carboxy-terminal group of D414 to [Formula: see text]-amino group of lysine residue within a neighboring polypeptide chain. We present an NMR resonance assignment of the calcium-free SPM, which displays characteristic features of intrinsically disordered proteins. Non-uniformly sampled 5D HN(CA)CONH, 4D HCBCACON, and HCBCANCO spectra were recorded to resolve poorly dispersed resonance frequencies of the disordered protein and 91 % of SPM residues were unambiguously assigned. Analysis of the chemical shifts revealed that two regions of the intrinsically disordered SPM (A95-S101 and R120-I127) have a tendency to form a helical structure, whereas the residues P1-D7 and G36-A40 have the propensity to adopt a [Formula: see text]-structure. PMID- 26138690 TI - A Pilot Study: The Effect of Roux-en-Y Gastric Bypass on the Serum MicroRNAs of the Type 2 Diabetes Patient. AB - PURPOSE: The purpose of this study was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on the serum microRNA of the type 2 diabetes (T2D) patient with different body mass indexes (BMI) or blood insulin and C-peptides. MATERIALS AND METHODS: Fifteen patients with T2D who elected to undergo gastric bypass surgery were separated into two groups, using BMI = 30 kg/m(2) as a reference point. Serum samples of venous blood were then collected before operation and 3 months after operation. RESULTS: After RYGB, there was an obvious change in the serum microRNA expression of both low- and high-BMI groups compared with those before operation. The expression of let-7, miR-24, miR-24-23a/b, miR-24-93, miR 24-26a, miR-24-151-3p, miR-24-425, miR-24-151-5p, miR-24-146a, and miR-24-103a were downregulated, whereas miR-4787-5p and miR-24-1281 were upregulated. Furthermore, there were more serum miroRNAs in the low-BMI group that changed notably, whereby miR-16, miR-17, miR-19b, miR-20a, miR-25, miR-106a/b, miR-107, miR-451, and miR-92a were downregulated, while miR-320a/b/c were upregulated. CONCLUSION: With improvement in fast glucose and insulin resistance of both low- and high-BMI groups, RYGB could modulate the expression of many serum microRNAs which are maybe associated with obesity, insulin secretion, and insulin resistance. However, in the low-BMI group, the expression of serum microRNA changed more obviously compared with the high-BMI group. This indicates that microRNA may play an important and unique role in the effect of RYGB on the improvement of insulin secretion and insulin resistance (IR), other than that played by decreased weight and body fat factors. PMID- 26138691 TI - Erratum to: Intranasal Nicotine Increases Postoperative Nausea and is Ineffective in Reducing Pain Following Laparoscopic Bariatric Surgery in Tobacco-Naive Females: A Randomized, Double Blind Trial. PMID- 26138692 TI - Laparoscopic Sleeve Gastrectomy Improves Olfaction Sensitivity in Morbidly Obese Patients. AB - BACKGROUND: Olfactory abilities of the patients are known to be altered by eating and metabolic disorders, including obesity. There are only a number of studies investigating the effect of obesity on olfaction, and there is limited data on the changes in olfactory abilities of morbidly obese patients after surgical treatment. Here we investigated the changes in olfactory abilities of 54 morbidly obese patients (M/F, 22/32; age range 19-57 years; body mass index (BMI) range 30.5-63.0 kg/m(2)) after laparoscopic sleeve gastrectomy. METHOD: A laparoscopic sleeve gastrectomy was performed by the same surgeon using five-port technique. Olfactory abilities were tested preoperatively and 1, 3, and 6 months after the surgery using a standardized Sniffin' Sticks Extended Test kit. RESULTS: Analyses of variance indicated statistically significant improvement in T, D, and I scores of morbidly obese patients within time factors (preoperative vs. 1, 3, and 6 months; 1 vs. 3 and 6 months; and 3 vs. 6 months; p < 0.001 for all). There was a statistically significant improvement in overall TDI scores with an increase from 25 to 41 during the 6 months follow-up period (p < 0.001 for all). CONCLUSIONS: Here, for the first time in literature, we were able to show the significant improvement in olfactory abilities of morbidly obese patients after laparoscopic sleeve gastrectomy. PMID- 26138693 TI - Role of the neutrophil chemorepellent soluble dipeptidyl peptidase IV in decreasing inflammation in a murine model of arthritis. AB - OBJECTIVE: To determine whether an intraarticular injection of the neutrophil chemorepellent dipeptidyl peptidase IV (DPPIV; CD26) can attenuate inflammation and decrease the severity of arthritis in a murine model. METHODS: DBA/1 mice were immunized with type II collagen/Freund's complete adjuvant to produce collagen-induced arthritis (CIA). On day 25 postimmunization, recombinant human DPPIV (rhDPPIV) or phosphate buffered saline was injected intraarticularly, and arthritis severity scores were recorded 3 times per week. The hind legs of mice in both groups were fixed, decalcified, paraffin embedded, and sectioned. Pathologic scores for inflammation and neutrophil infiltration were recorded on a scale of 1-8, and the number of neutrophils was determined by morphometric cell counts. In addition, Mac-2-positive macrophages and articular damage were assessed using anti-Mac-2 antibodies and histologic staining, respectively. RESULTS: Injection of rhDPPIV reduced the mean score of arthritis severity in mice with CIA. DPPIV treatment reduced the overall extent of inflammation and articular damage around the arthritic joint and periarticular tissue, and also decreased neutrophil and macrophage infiltration. CONCLUSION: A localized injection of the neutrophil chemorepellent DPPIV reduces inflammation and the severity of the disease in a murine model of arthritis. PMID- 26138694 TI - Health related quality of life in adolescents with chronic fatigue syndrome: a cross-sectional study. AB - AIM: To study health related quality of life (HRQOL) and depressive symptoms in adolescents with chronic fatigue syndrome (CFS) and to investigate in which domains their HRQOL and depressive symptoms differ from those of healthy adolescents. BACKGROUND AND OBJECTIVE: Several symptoms such as disabling fatigue, pain and depressive symptoms affect different life domains of adolescents with CFS. Compared to adolescents with other chronic diseases, young people with CFS are reported to be severely impaired, both physiologically and mentally. Despite this, few have investigated the HRQOL in this group. METHOD: This is a cross-sectional study on HRQOL including 120 adolescents with CFS and 39 healthy controls (HC), between 12 and 18 years. The Pediatric Quality of Life InventoryTM, 4.0 (PedsQL) was used to assess HRQOL. The Mood and Feelings Questionnaire assessed depressive symptoms. Data were collected between March 2010 and October 2012 as part of the NorCAPITAL project (Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial). Linear and logistic regression models were used in analysis, and all tests were two-sided. RESULTS: Adolescents with CFS reported significantly lower overall HRQOL compared to HCs. When controlling for gender differences, CFS patients scored 44 points lower overall HRQOL on a scale from 0-100 compared to HCs. The domains with the largest differences were interference with physical health (B = 59, 95 % CI -54 to -65) and school functioning (B = -52, 95 % CI -45 to -58). Both depressive symptoms and being a patient were independently associated with lower levels of HRQOL CONCLUSION: The difference in HRQOL between CFS patients and healthy adolescents was even larger than we expected. The large sample of adolescents with CFS in our study confirms previous findings from smaller studies, and emphasizes that CFS is a seriously disabling condition that has a strong impact on their HRQOL. Even though depressive symptoms were found in the group of patients, they could not statistically explain the poor HRQOL. PMID- 26138695 TI - Immunotherapy of HPV-associated cancer: DNA/plant-derived vaccines and new orthotopic mouse models. AB - Under the optimistic assumption of high-prophylactic HPV vaccine coverage, a significant reduction of cancer incidence can only be expected after decades. Thus, immune therapeutic strategies are needed for persistently infected individuals who do not benefit from the prophylactic vaccines. However, the therapeutic strategies inducing immunity to the E6 and/or E7 oncoprotein of HPV16 are more effective for curing HPV-expressing tumours in animal models than for treating human cancers. New strategies/technologies have been developed to improve these therapeutic vaccines. Our studies focussed on preparing therapeutic vaccines with low-cost technologies by DNA preparation fused to either plant virus or plant-toxin genes, such as saporin, and by plant-produced antigens. In particular, plant-derived antigens possess an intrinsic adjuvant activity that makes these preparations especially attractive for future development. Additionally, discrepancy in vaccine effectiveness between animals and humans may be due to non-orthotopic localization of animal models. Orthotopic transplantation leads to tumours giving a more accurate representation of the parent tumour. Since HPV can cause cancer in two main localizations, anogenital and oropharynx area, we developed two orthotopic tumour mouse models in these two sites. Both models are bioluminescent in order to follow up the tumour growth by imaging and are induced by cell injection without the need to intervene surgically. These models were utilized for immunotherapies with genetic or plant derived therapeutic vaccines. In particular, the head/neck orthotopic model appears to be very promising for studies combining chemo-radio-immune therapy that seems to be very effective in patients. PMID- 26138697 TI - Cancer Immunology Research: A Two-Year Anniversary. PMID- 26138696 TI - The chromosomal SezAT toxin-antitoxin system promotes the maintenance of the SsPI 1 pathogenicity island in epidemic Streptococcus suis. AB - Streptococcus suis has emerged as a causative agent of human meningitis and streptococcal toxic shock syndrome over the last years. The high pathogenicity of S. suis may be due in part to a laterally acquired pathogenicity island (renamed SsPI-1), which can spontaneously excise and transfer to recipients. Cells harboring excised SsPI-1 can potentially lose this island if cell division occurs prior to its reintegration; however, attempts to cure SsPI-1 from the host cells have been unsuccessful. Here, we report that an SsPI-1-borne Epsilon/Zeta toxin antitoxin system (designated SezAT) promotes SsPI-1 stability in bacterial populations. The sezAT locus consists of two closely linked sezT and sezA genes encoding a toxin and its cognate antitoxin, respectively. Overproduction of SezT induces a bactericidal effect that can be neutralized by co-expression of SezA, but not by its later action. When devoid of a functional SezAT system, large scale deletion of SsPI-1 is straightforward. Thus, SezAT serves to ensure inheritance of SsPI-1 during cell division, which may explain the persistence of epidemic S. suis. This report presents the first functional characterization of TA loci in S. suis, and the first biochemical evidence for the adaptive significance of the Epsilon/Zeta system in the evolution of pathogen virulence. PMID- 26138698 TI - Fc-Receptor Interactions Regulate Both Cytotoxic and Immunomodulatory Therapeutic Antibody Effector Functions. AB - Antibodies are now recognized as key therapeutic tools to combat most forms of malignancy. Although the first wave of therapeutic antibodies that emerged over two decades ago directly target tumor cells for killing, a new class of antibody therapies targeting immunoregulatory pathways to boost antitumor immune responses by activating the immune system is poised for clinical success. A notable common characteristic of both classes of therapeutic antibodies is the importance of the IgG Fc domain, which connects the fine specificity of an antibody with immune cells that mediate antibody-triggered effector functions through their engagement of Fc receptor (FcR) family members. It is now clear that multiple variables, including the nature of the target molecules, the local presence of effector cells, and the expression patterns of FcRs, will dictate whether and how an antibody will necessitate interactions with FcRs to mediate optimal therapeutic effects. Thus, through careful in vivo mechanistic analyses of individual therapeutic antibodies, Fc domains engineered for optimal engagement of the appropriate cellular FcRs must be designed to maximize clinical success. PMID- 26138699 TI - Parent-child discrepancies in the assessment of children's and adolescents' happiness. AB - In this study, we assessed parent-child agreement in the perception of children's general happiness or well-being in typically developing children (10- and 11-year olds, n = 172) and adolescents (15- and 16-year-olds, n = 185). Despite parent and child reporters providing internally consistent responses in the General Happiness single-item scale and the Oxford Happiness Questionnaire-Short Form, their perceptions about children's and adolescents' general happiness did not correlate. Parents of 10- and 11-year-olds significantly overestimated children's happiness, supporting previous literature on the parents' positivity bias effect. However, parents of 15- and 16-year-olds showed the reverse pattern by underestimating adolescents' happiness. Furthermore, parents' self-reported happiness or well-being (reported 6 months later) significantly correlated with their estimations of children's and adolescents' happiness. Therefore, these results suggest a potential parents' "egocentric bias" when estimating their children's happiness. These findings are discussed in terms of their theoretical and applied implications for research into child-parent relationships. PMID- 26138701 TI - Exploring Patients' Experiences of Eating Disorder Treatment Services From a Motivational Perspective. AB - This study employed qualitative methods to explore eating disorder (ED) patients' perspectives on their treatment experiences to gain insight into those factors that influenced their motivational trajectory. Semistructured interviews were conducted with a purposive female sample of current (N = 11) and discharged (N = 3) ED service users, aged 18 to 31 years (M = 23.21, SD = 4.19). An interpretive thematic analytic approach, comprising both inductive and deductive methods of analysis, was employed to identify key themes in the data. Self-determination theory (SDT) provided a conceptual lens for analyzing data. Participants highlighted that factors such as physical design and nature of the treatment environment, relational aspects of care, and therapeutic methods all played a role in treatment engagement. The findings highlight ways in which current ED services might more effectively meet the needs of service users and support the utility of applying SDT to the study of motivational dynamics in the treatment of EDs. PMID- 26138700 TI - The Effects of Stress on Cognitive Aging, Physiology and Emotion (ESCAPE) Project. AB - BACKGROUND: Despite evidence that psychological stress is an important risk factor for age-related cognitive loss, little research has directly evaluated psychological and physiological mediators of the relationship between stressful experiences and cognitive function. A key objective of the ESCAPE (Effects of Stress on Cognitive Aging, Physiology, and Emotion) project is to evaluate whether engaging in stress-related unconstructive repetitive thought (URT) is a pathway through which stressful experiences negatively affect cognitive health over the short- and long-term. Over the short-term, we hypothesize that engaging in URT will deplete attentional resources and result in worse cognitive performance in daily life. Over the long-term, we expect that the effects of chronic stress, from repeated exposure to stressors and regular engagement in URT, will be apparent in dysregulated hypothalamic-pituitary-adrenal (HPA) axis function and inflammation. Over time, stress-related physiological dysregulation will result in accelerated cognitive decline. METHODS/DESIGN: This study utilizes a prospective longitudinal measurement-burst design. A systematic probability sample of participants aged 25 to 65 is recruited from residents of the Bronx, NY. Consenting participants complete a baseline assessment and follow-up waves at 9, 18, and 27 months post-baseline. At each wave, participants complete a 14 day measurement burst of brief surveys and cognitive assessments delivered via study smartphones during daily life. Participants provide saliva samples four times each day for five days during the measurement burst and fasting blood samples at the end of each burst from which cortisol and dehydroepiandrosterone sulfate (DHEAS), circulating inflammatory markers, and stimulated inflammatory responses to lipopolysaccharide in whole blood are determined. DISCUSSION: This study takes a multi-pronged approach to assessing stress (i.e., early adversity, chronic strains, major events, daily hassles), psychological mediators (e.g., URT), biological mechanisms (i.e., HPA function, inflammation) and outcomes across different time-scales (i.e., momentary cognitive performance, cognitive decline across years). The systematic probability sample is locally representative and can be compared with national norms on key markers of health and well-being. The findings will improve our understanding of how environmental, psychological, and physiological stress-related influences accumulate to affect cognitive health and identify potential targets (e.g., URT, inflammation) for prevention and intervention promoting cognitive health. PMID- 26138702 TI - Fructose content of low calorie diets: effect on cardiometabolic risk factors in obese women with polycystic ovarian syndrome: a randomized controlled trial. AB - We aimed to examine whether a whole-grain crispbread (CB) low-fructose, low calorie diet (LCD) might be superior to a traditional LCD based on fructose-rich liquid meal replacements (LMRs) with respect to improvement of various cardiometabolic risk factors and reproductive hormones. Parallel-group randomised controlled clinical trial. Morbidly obese women with polycystic ovarian syndrome (PCOS) were randomised to either an 8-week CB-LCD or LMR-LCD (900-1100 kcal/day, fructose 17 g/day or 85 g/day). A total of 51 women completed the study. Body weight, fat mass and waist circumference reduced by mean (s.d.) 10.0 (4.8) kg, 7.4 (4.2) kg and 8.5 (4.4) cm, with no significant differences between groups. Total-cholesterol, HDL-cholesterol and Apo-A1 were significantly reduced within both groups (all P values <0.01), with no significant between-group differences. The triacylglycerol and LDL-cholesterol levels were reduced within the LMR group only, with no significant between-group differences. Blood pressure and most measures of glucose metabolism improved significantly in both diet groups, with no significant between-group difference. Uric acid levels rose by 17.7 (46.4) and 30.6 (71.5) MUmol/l in the CB and LMR group, respectively, with no significant difference between groups. Gastrointestinal discomfort was significantly and equally reduced in both intervention groups. Free testosterone index was reduced in both groups, with no significant difference between groups. Morbidly obese women with PCOS who underwent either an 8-week low or high-fructose LCD-diet had similar changes in various cardiometabolic risk factors and reproductive hormones. Registration at ClinicalTrials.gov: NCT00779571. PMID- 26138703 TI - Prevalence of secondary hyperparathyroidism in patients with stage 3 and 4 chronic kidney disease seen in internal medicine. AB - OBJECTIVE: Despite the high prevalence of chronic kidney disease in the elderly population, few data are available on the frequency of secondary hyperparathyroidism in the Spanish population affected by this problem. We undertook a study on this issue in patients attending the internal medicine departments in our area. DESIGN AND METHODS: An observational, cross-sectional survey performed at internal medicine departments on 415 patients with stage 3 and 4 chronic kidney disease. Clinical history and risk factors were collected using a standardized protocol. Serum creatinine, phosphate, calcium, intact parathormone (PTH) and 25-hydroxy-cholecalciferol (25-OH-vitD) levels were measured in all patients. RESULTS: Among stage 3 patients, 62.9% had PTH levels >=70pg/mL and 32.7% levels >=110pg/mL. Median PTH level in stage 4 patients was 120pg/mL (p <0.001), and 77.9% of these patients had PTH >=70pg/mL (p <0.001) and 54.1% >=110pg/mL (p=0.015). Adequate 25-hydroxy-cholecalciferol levels were found in only 7.2% of stage 3 patients and 4.1% of stage 4 patients. Only 7.2% of stage 3 patients had hyperphosphatemia, as compared to 25.4% of stage 4 patients (p <0.001). CONCLUSIONS: Hyperparathyroidism is a common complication of stage 3 and 4 chronic kidney disease which is not associated to detectable changes in serum calcium and phosphate levels. It is therefore advisable to measure PTH levels in all patients with decreased glomerular filtration rate. PMID- 26138705 TI - Poly(L-lactide)/halloysite nanotube electrospun mats as dual-drug delivery systems and their therapeutic efficacy in infected full-thickness burns. AB - In this study, poly(L-lactide) (PLLA)/halloysite nanotube (HNT) electrospun mats were prepared as a dual-drug delivery system. HNTs were used to encapsulate polymyxin B sulphate (a hydrophilic drug). Dexamethasone (a hydrophobic drug) was directly dissolved in the PLLA solution. The drug-loaded HNTs with optimised encapsulation efficiency were then mixed with the PLLA solution for subsequent electrospinning to form composite dual-drug-loaded fibre mats. The structure, morphology, degradability and mechanical properties of the electrospun composite mats were characterised in detail. The results showed that the HNTs were uniformly distributed in the composite PLLA mats. The HNTs content in the mats could change the morphology and average diameter of the electrospun fibres. The HNTs improved both the tensile strength of the PLLA electrospun mats and their degradation ratio. The drug-release kinetics of the electrospun mats were investigated using ultraviolet-visible spectrophotometry. The HNTs/PLLA ratio could be varied to adjust the release of polymyxin B sulphate and dexamethasone. The antibacterial activity in vitro of the mats was evaluated using agar diffusion and turbidimetry tests, which indicated the antibacterial efficacy of the dual-drug delivery system against Gram-positive and -negative bacteria. Healing in vivo of infected full-thickness burns and infected wounds was investigated by macroscopic observation, histological observation and immunohistochemical staining. The results indicated that the electrospun mats were capable of co-loading and co-delivering hydrophilic and hydrophobic drugs, and could potentially be used as novel antibacterial wound dressings. PMID- 26138704 TI - The anti-fibrotic effect of inhibition of TGFbeta-ALK5 signalling in experimental pulmonary fibrosis in mice is attenuated in the presence of concurrent gamma herpesvirus infection. AB - TGFbeta-ALK5 pro-fibrotic signalling and herpesvirus infections have been implicated in the pathogenesis and exacerbation of pulmonary fibrosis. In this study we addressed the role of TGFbeta-ALK5 signalling during the progression of fibrosis in a two-hit mouse model of murine gamma-herpesvirus 68 (MHV-68) infection on the background of pre-existing bleomycin-induced pulmonary fibrosis. Assessment of total lung collagen levels in combination with ex vivo micro computed tomography (uCT) analysis of whole lungs demonstrated that MHV-68 infection did not enhance lung collagen deposition in this two-hit model but led to a persistent and exacerbated inflammatory response. Moreover, uCT reconstruction and analysis of the two-hit model revealed distinguishing features of diffuse ground-glass opacities and consolidation superimposed on pre-existing fibrosis that were reminiscent of those observed in acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Virally-infected murine fibrotic lungs further displayed evidence of extensive inflammatory cell infiltration and increased levels of CCL2, TNFalpha, IL-1beta and IL-10. Blockade of TGFbeta-ALK5 signalling attenuated lung collagen accumulation in bleomycin-alone injured mice, but this anti-fibrotic effect was reduced in the presence of concomitant viral infection. In contrast, inhibition of TGFbeta-ALK5 signalling in virally-infected fibrotic lungs was associated with reduced inflammatory cell aggregates and increased levels of the antiviral cytokine IFNgamma. These data reveal newly identified intricacies for the TGFbeta-ALK5 signalling axis in experimental lung fibrosis, with different outcomes in response to ALK5 inhibition depending on the presence of viral infection. These findings raise important considerations for the targeting of TGFbeta signalling responses in the context of pulmonary fibrosis. PMID- 26138706 TI - A Longitudinal Analysis of Changes in Job Control and Mental Health. AB - Deteriorating job control has been previously shown to predict poor mental health. The impact of improvement in job control on mental health is less well understood, yet it is of policy significance. We used fixed-effects longitudinal regression models to analyze 10 annual waves of data from a large Australian panel survey (2001-2010) to test within-person associations between change in self-reported job control and corresponding change in mental health as measured by the Mental Component Summary score of Short Form 36. We found evidence of a graded relationship; with each quintile increase in job control experienced by an individual, the person's mental health increased. The biggest improvement was a 1.55-point increase in mental health (95% confidence interval: 1.25, 1.84) for people moving from the lowest (worst) quintile of job control to the highest. Separate analyses of each of the component subscales of job control-decision authority and skill discretion-showed results consistent with those of the main analysis; both were significantly associated with mental health in the same direction, with a stronger association for decision authority. We conclude that as people's level of job control increased, so did their mental health, supporting the value of targeting improvements in job control through policy and practice interventions. PMID- 26138707 TI - Hypercortisolemic Depressed Women: Lean but Viscerally Obese? AB - BACKGROUND: Activation of the hypothalamic-pituitary-adrenal (HPA) system in depressed patients has been related to visceral adiposity. In contrast, low HPA system activity is associated with increased body fat in the general population. Our study intended to clarify whether HPA system activity is related to body weight and composition in depressed inpatients. METHODS: In a cohort of 51 female and 20 male depressed inpatients, we measured saliva cortisol (HPA system activity), body mass index (BMI), waist circumference as well as body composition as reflected by bioimpedance. RESULTS: In female patients, cortisol in saliva was negatively associated with fat-to-muscle ratio and BMI. CONCLUSION: In depressed inpatients, especially women, there is evidence that activation of the HPA system is related to relatively low body weight and low body fat content. PMID- 26138708 TI - Contrasting effects of biochar versus manure on soil microbial communities and enzyme activities in an Aridisol. AB - Biochar can increase microbial activity, alter microbial community structure, and increase soil fertility in arid and semi-arid soils, but at relatively high rates that may be impractical for large-scale field studies. This contrasts with organic amendments such as manure, which can be abundant and inexpensive if locally available, and thus can be applied to fields at greater rates than biochar. In a field study comparing biochar and manure, a fast pyrolysis hardwood biochar (22.4 Mg ha(-1)), dairy manure (42 Mg ha(-1) dry wt), a combination of biochar and manure at the aforementioned rates, or no amendment (control) was applied to an Aridisol (n=3) in fall 2008. Plots were annually cropped to corn (Zea maize L.). Surface soils (0-30 cm) were sampled directly under corn plants in late June 2009 and early August 2012, and assayed for microbial community fatty acid methyl ester (FAME) profiles and six extracellular enzyme activities involved in soil C, N, and P cycling. Arbuscular mycorrhizal (AM) fungal colonization was assayed in corn roots in 2012. Biochar had no effect on microbial biomass, community structure, extracellular enzyme activities, or AM fungi root colonization of corn. In the short-term, manure amendment increased microbial biomass, altered microbial community structure, and significantly reduced the relative concentration of the AM fungal biomass in soil. Manure also reduced the percent root colonization of corn by AM fungi in the longer-term. Thus, biochar and manure had contrasting short-term effects on soil microbial communities, perhaps because of the relatively low application rate of biochar. PMID- 26138709 TI - Effect of biochar on reclaimed tidal land soil properties and maize (Zea mays L.) response. AB - Reclaimed tidal land soil (RTLS) often contains high levels of soluble salts and exchangeable Na that can adversely affect plant growth. The current study examined the effect of biochar on the physicochemical properties of RTLS and subsequently the influence on plant growth performance. Rice hull derived biochar (BC) was applied to RTLS at three different rates (1%, 2%, and 5% (w/w)) and maize (Zea mays L.) subsequently cultivated for 6weeks. While maize was cultivated, 0.1% NaCl solution was supplied from the bottom of the pots to simulate the natural RTLS conditions. Biochar induced changes in soil properties were evaluated by the water stable aggregate (WSA) percentage, exchangeable sodium percentage (ESP), soil organic carbon contents, cation exchange capacity, and exchangeable cations. Plant response was measured by growth rate, nutrient contents, and antioxidant enzyme activity of ascorbate peroxidase (APX) and glutathione reductase (GR). Application of rice hull derived biochar increased the soil organic carbon content and the percentage of WSA by 36-69%, while decreasing the ESP. The highest dry weight maize yield was observed from soil which received 5% BC (w/w), which was attributed to increased stability of water stable aggregates and elevated levels of phosphate in BC incorporated soils. Moreover, increased potassium, sourced from the BC, induced mitigation of Na uptake by maize and consequently, reduced the impact of salt stress as evidenced by overall declines in the antioxidant activities of APX and GR. PMID- 26138710 TI - Biochars impact on water infiltration and water quality through a compacted subsoil layer. AB - Soils in the SE USA Coastal Plain region frequently have a compacted subsoil layer (E horizon), which is a barrier for water infiltration. Four different biochars were evaluated to increase water infiltration through a compacted horizon from a Norfolk soil (fine-loamy, kaolinitic, thermic, Typic Kandiudult). In addition, we also evaluated biochars effect on water quality. Biochars were produced by pyrolysis at 500 degrees C from pine chips (Pinus taeda), poultry litter (Gallus domesticus) feedstocks, and as blends (50:50 and 80:20) of pine chip:poultry litter. Prior to pyrolysis, the feedstocks were pelletized and sieved to >2-mm pellets. Each biochar was mixed with the subsoil at 20 g/kg (w/w) and the mixture was placed in columns. The columns were leached four times with Milli-Q water over 128 d of incubation. Except for the biochar produced from poultry litter, all other applied biochars resulted in significant water infiltration increases (0.157-0.219 mL min(-1); p<0.05) compared to the control (0.095 mL min(-1)). However, water infiltration in each treatment were influenced by additional water leaching. Leachates were enriched in PO4, SO4, Cl, Na, and K after addition of poultry litter biochar, however, their concentrations declined in pine chip blended biochar treatments and after multiple leaching. Adding biochars (except 100% poultry litter biochar) to a compacted subsoil layer can initially improve water infiltration, but, additional leaching revealed that the effect remained only for the 50:50 pine chip:poultry litter blended biochar while it declined in other biochar treatments. PMID- 26138711 TI - A cannabinoid-intoxicated child treated with dexmedetomidine: a case report. AB - INTRODUCTION: In the last 20 years, the rate of exposure to marijuana has increased dramatically, even in the pediatric population. Effects of intoxication are variable, more severe neurological symptoms can be observed following ingestion, thus hospital or intensive care unit admission is often required. Usually cannabinoids intoxicated patients are treated with administration of benzodiazepines or opioids, accepting the related risk of intubation and mechanical ventilation. Dexmedetomidine is a highly selective alpha2-adrenergic receptor agonist, with no effect on the respiratory drive and pattern and produces a good level of sedation, allowing to avoid the administration of other sedatives. To our knowledge, this is the first reported case of dexmedetomidine use to support a cannabis intoxicated patient. CASE PRESENTATION: A 19-month-old Caucasian boy was presented to our emergency department. At the time of his arrival, he was somnolent with paroxysms of agitation, breathing spontaneously and hemodynamically stable. The results of all investigations were negative, but the result of the immunochemical screening of his urine was positive for Delta(9) tetrahydrocannabinol. The patient was admitted to the pediatric intensive care unit and treated with a continuous infusion of dexmedetomidine. CONCLUSIONS: Dexmedetomidine is a fairly safe and effective antidote for pediatric marijuana or natural cannabinoid exposures. Its properties and potential to allow for "cooperative" sedation make it a more attractive choice with fewer side effects than benzodiazepines or opioids. PMID- 26138713 TI - Probing the common alkali metal affinity of native and variously methylated beta cyclodextrins by combining electrospray-tandem mass spectrometry and molecular modeling. AB - In the study herein, we investigated the solution and gas phase affinity of native and variously methylated beta-cyclodextrins (CDs) as hosts towards three common alkali metals as guests namely lithium, sodium and potassium. For this purpose, two complementary approaches have been employed: electrospray-tandem mass spectrometry (ESI-MS/MS) with two energetic regimes: Collision Induced Dissociation (CID) and Higher Collision Dissociation (HCD), respectively, and DFT molecular modeling. These approaches have been achieved by taking into account the interaction of either one or two alkali metals with the host molecules. The results showed a good agreement between experimental and theoretical data. It was demonstrated that increasing the methylation degree strengthened the gas phase affinity towards all studied alkali metals. Furthermore, it was established that the cation selectivity was Na(+) > Li(+) > K(+) and Li(+) > Na(+) > K(+) for the solution and gas phase, respectively. PMID- 26138712 TI - Clinical realism: a new literary genre and a potential tool for encouraging empathy in medical students. AB - BACKGROUND: Empathy has been re-discovered as a desirable quality in doctors. A number of approaches using the medical humanities have been advocated to teach empathy to medical students. This paper describes a new approach using the medium of creative writing and a new narrative genre: clinical realism. METHODS: Third year students were offered a four week long Student Selected Component (SSC) in Narrative Medicine and Creative Writing. The creative writing element included researching and creating a character with a life-changing physical disorder without making the disorder the focus of the writing. The age, gender, social circumstances and physical disorder of a character were randomly allocated to each student. The students wrote repeated assignments in the first person, writing as their character and including details of living with the disorder in all of their narratives. This article is based on the work produced by the 2013 cohort of students taking the course, and on their reflections on the process of creating their characters. Their output was analysed thematically using a constructivist approach to meaning making. RESULTS: This preliminary analysis suggests that the students created convincing and detailed narratives which included rich information about living with a chronic disorder. Although the writing assignments were generic, they introduced a number of themes relating to illness, including stigma, personal identity and narrative wreckage. Some students reported that they found it difficult to relate to "their" character initially, but their empathy for the character increased as the SSC progressed. CONCLUSION: Clinical realism combined with repeated writing exercises about the same character is a potential tool for helping to develop empathy in medical students and merits further investigation. PMID- 26138714 TI - Liberia confirms Ebola case two months after being declared free of the disease. PMID- 26138716 TI - Elcatonin attenuates disuse osteoporosis after fracture fixation of tubular bone in rats. AB - BACKGROUND: Elcatonin (ECT) is used to prevent and treat osteoporosis. However, little is known about its effect on the disuse osteoporosis (DOP). The aim of this study is to evaluate the effect of ECT on DOP caused by fracture fixation. METHODS: Forty-five male Sprague-Dawley (SD) rats, aged 6 weeks, were randomly allocated into three groups: the control group without surgery and elcatonin treatment (CTR, n = 15), the surgery group without elcatonin treatment (SUR, n = 15), and the surgery group which received elcatonin subcutaneously (SUR + ECT, n = 15). Surgery was produced by cutting the midshaft of the right femur transversely, fixing with stainless intramedullary needle, and immobilizing the right leg. All the proximal tibias from the random five rats in each group were harvested and investigated by evaluating bone mineral density (BMD), X-ray images, and histological staining respectively at the 4th, 8th, and 12th weeks after surgery. RESULTS: Both of the SUR and SUR + ECT groups obviously exhibited lower BMD values compared to the CTR group; however, the SUR + ECT group showed significantly higher BMD values (p < 0.001, p < 0.05, and p < 0.05) than the SUR group at each time point after surgery. Moreover, similar changes were observed between these groups when examining the radiographs and hematoxylin and eosin (HE) staining. CONCLUSIONS: Elcatonin attenuates disuse osteoporosis after fractures in rats, which may provide a new avenue to prevent and treat disuse osteoporosis after surgery in clinic. PMID- 26138717 TI - 2015 International Working Group on the Diabetic Foot Guidance on the prevention and management of foot problems in diabetes. PMID- 26138715 TI - Randomized controlled trial of computer-based treatment of social cognition in schizophrenia: the TRuSST trial protocol. AB - BACKGROUND: Schizophrenia is a severe and chronic medical condition, characterized by positive and negative symptoms, as well as pervasive social cognitive deficits. Despite the functional significance of the social cognition deficits affecting many aspects of daily living, such as social relationships, occupational status, and independent living, there is still no effective treatment option for these deficits, which is applied as standard of care. To address this need, we developed a novel, internet-based training program that targets social cognition deficits in schizophrenia (SocialVille). Preliminary studies demonstrate the feasibility and initial efficacy of Socialville in schizophrenia patients (Nahum et al., 2014). The purpose of the current trial (referred to as the TReatment of Social cognition in Schizophrenia Trial or TRuSST) is to compare SocialVille to an active control training condition, include a larger sample of patients, and assess both social cognitive functioning, and functional outcomes. METHODS/DESIGN: We will employ a multi site, longitudinal, blinded, randomized controlled trial (RCT) design with a target sample of 128 patients with schizophrenia. Patients will perform, at their home or in clinic, 40 sessions of either the SocialVille training program or an active control computer game condition. Each session will last for 40-45 minutes/day, performed 3-5 days a week, over 10-12 weeks, totaling to 30 hours of training. Patients will be assessed on a battery of social cognitive, social functioning and functional outcomes immediately before training, mid-way through training (after 20 training sessions) and at the completion of the 40 training sessions. DISCUSSION: The strengths of this protocol are that it tests an innovative, internet-based treatment that targets fundamental social cognitive deficits in schizophrenia, employs a highly sensitive and extensive battery of functional outcome measures, and incorporates a large sample size in an RCT design. TRIAL REGISTRATION: ClinicalTrials.gov NCT02246426 Registered 16 September 2014. PMID- 26138720 TI - Phenotypic expression is a prerequisite for malignant arrhythmic events and sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy. AB - AIMS: Whether a desmosomal (DS)-gene defect may in itself induce life-threatening ventricular arrhythmias regardless of phenotypic expression of arrhythmogenic right ventricular cardiomyopathy (ARVC) is still debated. This prospective study evaluated the long-term outcome of DS-gene mutation carriers in relation to the ARVC phenotypic expression. METHODS AND RESULTS: The study population included 116 DS-gene mutation carriers [49% males; median age 33 years (16-48 years)] without prior sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The incidence of the arrhythmic endpoint, including sudden cardiac death (SCD), aborted SCD, sustained VT, and appropriate implantable cardioverter defibrillator (ICD) intervention was evaluated prospectively and stratified by the presence of ARVC phenotype and risk factors (syncope, ventricular dysfunction, and non-sustained VT). At enrolment, 40 of 116 (34%) subjects fulfilled the criteria for definite ARVC while the remaining were either borderline or phenotype negatives. During a median follow-up of 8.5 (5-12) years, 10 patients (9%) had arrhythmic events (0.9%/year). The event rate was 2.3%/year among patients with definite ARVC and 0.2%/year among borderline or phenotype negative patients (P = 0.002). In patients with definite ARVC, the incidence of arrhythmias was higher in those with >=1 risk factors (4.1%/year) than in those with no risk factors (0.4%/year, P = 0.02). Mortality was 0.2%/year (1 heart failure death and 1 SCD). CONCLUSIONS: The ARVC phenotypic expression is a prerequisite for the occurrence of life-threatening arrhythmias in DS-gene mutation carriers. The vast majority of malignant arrhythmic events occurred in patients with an overt disease phenotype and major risk factors suggesting that this subgroup most benefits from ICD therapy. PMID- 26138721 TI - Expression Levels of Myostatin and Matrix Metalloproteinase 14 mRNAs in Uterine Leiomyoma are Correlated With Dysmenorrhea. AB - Uterine leiomyoma is the most common benign neoplasm of female reproductive system, found in about 50% of women in reproductive age. The mechanisms of leiomyoma growth include cell proliferation, which is modulated by growth factors, and deposition of extracellular matrix (ECM). Activin A and myostatin are growth factors that play a role in proliferation of leiomyoma cells. Matrix metalloproteinases (MMPs) are known for their ability to remodel the ECM in different biological systems. The aim of this study was to evaluate the expression levels of activin betaA-subunit, myostatin, and MMP14 messenger RNAs (mRNAs) in uterine leiomyomas and the possible correlation of these factors with clinical features of the disease. Matrix metalloproteinase 14 was highly expressed in uterine leiomyoma and correlated with myostatin and activin A mRNA expression. Moreover, MMP14 and myostatin mRNA expression correlated significantly and directly with the intensity of dysmenorrhea. Overall, the present findings showed that MMP14 mRNA is highly expressed in uterine leiomyoma, where it correlates with the molecular expression of growth factors and is further increased in cases of intense dysmenorrhea. PMID- 26138722 TI - Binding Force Dynamics of Streptococcus mutans-glucosyltransferase B to Candida albicans. AB - Candida albicans cells are often detected with Streptococcus mutans in plaque biofilms from children affected with early childhood caries. The coadhesion between these 2 organisms appears to be largely mediated by the S. mutans-derived exoenzyme glucosyltransferase B (GtfB); GtfB readily binds to C. albicans cells in an active form, producing glucans locally that provide enhanced binding sites for S. mutans. However, knowledge is limited about the mechanisms by which the bacterial exoenzyme binds to and functions on the fungal surface to promote this unique cross-kingdom interaction. In this study, we use atomic force microscopy to understand the strength and binding dynamics modulating GtfB-C. albicans adhesive interactions in situ. Single-molecule force spectroscopy with GtfB functionalized atomic force microscopy tips demonstrated that the enzyme binds with remarkable strength to the C. albicans cell surface (~2 nN) and showed a low dissociation rate, suggesting a highly stable bond. Strikingly, the binding strength of GtfB to the C. albicans surface was ~2.5-fold higher and the binding stability, ~20 times higher, as compared with the enzyme adhesion to S. mutans. Furthermore, adhesion force maps showed an intriguing pattern of GtfB binding. GtfB adhered heterogeneously on the surface of C. albicans, showing a higher frequency of adhesion failure but large sections of remarkably strong binding forces, suggesting the presence of GtfB binding domains unevenly distributed on the fungal surface. In contrast, GtfB bound uniformly across the S. mutans cell surface with less adhesion failure and a narrower range of binding forces (vs. the C. albicans surface). The data provide the first insights into the mechanisms underlying the adhesive and mechanical properties governing GtfB interactions with C. albicans. The strong and highly stable GtfB binding to C. albicans could explain, at least in part, why this bacterially derived exoenzyme effectively modulates this virulent cross-kingdom interaction. PMID- 26138723 TI - Erratum: Clinical skills development in student-run free clinic volunteers: a multi-trait, multi-measure study. PMID- 26138724 TI - The Association between Sleep Duration and Non-Alcoholic Fatty Liver Disease among Japanese Men and Women. AB - OBJECTIVE: To examine the relationship between sleep duration and non-alcoholic fatty liver disease (NAFLD). METHODS: We evaluated 3,968 subjects who underwent health check-ups from June 2012 to May 2013 at the Watari Hospital Health Center in Fukushima Prefecture in Japan. Fatty liver was detected by ultrasonography. Sleep duration and lifestyle factors were estimated using a questionnaire. Sleep duration was categorized into the following groups: <= 6, 6 to <= 7, >7 to <= 8, and >8 h. The four sleep duration groups were compared using the chi(2) test and Kruskal-Wallis test. RESULTS: In total, 2,172 subjects were enrolled. The overall prevalence of NAFLD was 29.6% (men, 38.0%; women, 25.3%). The proportion of NAFLD tended to decrease as sleep duration increased in men. The proportion with NAFLD was lowest in the group with a sleep duration of 6 to <= 7 h and highest in the groups with sleep durations of <= 6 and >8 h in women. The distribution showed a U-shaped curve. The age-adjusted odds ratio (OR) (95% confidence interval (CI)) for subjects with NAFLD with a sleep duration <= 6 h compared to the reference (6 to <= 7 h) was 1.44 (1.06-1.96) in women. CONCLUSION: Sleep shortage tends to be associated with NAFLD in women and may be mediated by body adiposity. PMID- 26138725 TI - Liraglutide improves weight loss in people who are overweight or obese, study shows. PMID- 26138726 TI - Investigating neural mechanisms of change of cognitive behavioural therapy for chronic fatigue syndrome: a randomized controlled trial. AB - BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by profound and disabling fatigue with no known somatic explanation. Cognitive behavioral therapy (CBT) has proven to be a successful intervention leading to a reduction in fatigue and disability. Based on previous neuroimaging findings, it has been suggested that central neural mechanisms may underlie CFS symptoms and play a role in the change brought on by CBT. In this randomized controlled trial we aim to further investigate the neural mechanisms that underlie fatigue in CFS and their change by CBT. METHODS/DESIGN: We will conduct a randomized controlled trial in which we collect anatomical and functional magnetic resonance imaging (MRI) measures from female CFS patients before and after CBT (N = 60) or waiting list (N = 30) and compare these with measures from age and education matched healthy controls (N = 30). By including a large treatment group we will also be able to compare patients that benefit from CBT with those that do not. In addition, to further investigate the role of endocrine and immune biomarkers in CFS, we will determine cortisol and cytokine concentrations in blood, hair and/or saliva. DISCUSSION: This project creates an unique opportunity to enhance our understanding of CFS symptoms and its change by CBT in terms of neuroanatomical, neurofunctional, endocrinological and immunological mechanisms and can help to further improve future treatments strategies. TRIAL REGISTRATION: Dutch Trial Register #15852. Registered 9 December 2013 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4311 ). PMID- 26138727 TI - Chemokine CXCL1-Mediated Neutrophil Trafficking in the Lung: Role of CXCR2 Activation. AB - The chemokine CXCL1 and its receptor CXCR2 play a crucial role in host immune response by recruiting and activating neutrophils for microbial killing at the tissue site. Dysregulation in this process has been implicated in collateral tissue damage causing disease. CXCL1 reversibly exists as monomers and dimers, and it has been proposed that distinct monomer and dimer activities and the monomer-dimer equilibrium regulate the neutrophil function. However, the molecular mechanisms linking the CXCL1/CXCR2 axis and the neutrophil 'beneficial' and 'destructive' phenotypes are not known. In this study, we characterized neutrophil trafficking and its consequence in the mouse lung by the CXCL1 wild type (WT), which exists as monomers and dimers, and by a nondissociating dimer. Whereas the WT, compared to the dimer, was more active at low doses, both the WT and the dimer elicited a large neutrophil efflux at high doses. Importantly, robust neutrophil recruitment elicited by the WT or dimer was not detrimental to lung tissue integrity and, further, could not be correlated to surface CXCR2 levels. We conclude that the CXCL1 monomer-dimer distribution and receptor interactions are highly coupled and regulate neutrophil trafficking and that injury in the context of disease is a consequence of inappropriate CXCR2 activation at the target tissue and not due to mechanical forces exerted by neutrophils during recruitment. PMID- 26138729 TI - Exploring trends in and determinants of educational inequalities in self-rated health. AB - AIMS: Educational inequalities in self-rated health (SRH) in European welfare countries are documented, but recent trends in these inequalities are less well understood. We examined educational inequalities in SRH in different age groups, and the contribution of selected material, behavioural and psychosocial determinants from 2000 to 2008. METHODS: Data were derived from cross-sectional surveys conducted in 2000, 2004 and 2008 including 37,478, 34,876 and 32,982 respondents, respectively, aged 25-75 in mid-Sweden. Inequalities were analysed by age-standardized and age-stratified rate ratios of poor SRH and age standardized prevalence of determinants, and contribution of determinants by age adjusted logistic regression. RESULTS: Relative educational inequalities in SRH increased among women from 2000 (rate ratio (RR) 1.70, 95% CI 1.55-1.85) to 2008 (RR 2.07, 95% CI 1.90-2.26), but were unchanged among men (RR 1.91-2.01). The increase among women was mainly due to growing inequalities in the age group 25 34 years. In 2008, significant age differences emerged with larger inequalities in the youngest compared with the oldest age group in both genders. All determinants were more prevalent in low educational groups; the most prominent were lack of a financial buffer, smoking and low optimism. Educational differences were unchanged over the years for most determinants. In all three surveys, examined determinants together explained a substantial part of the educational inequalities in SRH. CONCLUSIONS: Increased relative educational health inequalities among women, and persisting inequalities among men, were paralleled by unchanged, large differences in material/structural, behavioural and psychosocial factors. Interventions to reduce these inequalities need to focus on early mid-life. PMID- 26138728 TI - The influence of mild carbon dioxide on brain functional homotopy using resting state fMRI. AB - Homotopy reflects the intrinsic functional architecture of the brain through synchronized spontaneous activity between corresponding bilateral regions, measured as voxel mirrored homotopic connectivity (VMHC). Hypercapnia is known to have clear impact on brain hemodynamics through vasodilation, but have unclear effect on neuronal activity. This study investigates the effect of hypercapnia on brain homotopy, achieved by breathing 5% carbon dioxide (CO2 ) gas mixture. A total of 14 healthy volunteers completed three resting state functional MRI (RS fMRI) scans, the first and third under normocapnia and the second under hypercapnia. VMHC measures were calculated as the correlation between the BOLD signal of each voxel and its counterpart in the opposite hemisphere. Group analysis was performed between the hypercapnic and normocapnic VMHC maps. VMHC showed a diffused decrease in response to hypercapnia. Significant regional decreases in VMHC were observed in all anatomical lobes, except for the occipital lobe, in the following functional hierarchical subdivisions: the primary sensory motor, unimodal, heteromodal, paralimbic, as well as in the following functional networks: ventral attention, somatomotor, default frontoparietal, and dorsal attention. Our observation that brain homotopy in RS-fMRI is affected by arterial CO2 levels suggests that caution should be used when comparing RS-fMRI data between healthy controls and patients with pulmonary diseases and unusual respiratory patterns such as sleep apnea or chronic obstructive pulmonary disease. PMID- 26138730 TI - Initial experience of coiling cerebral aneurysms using the new Comaneci device. AB - We present our initial patient experience with an innovative temporary bridging device, the Comaneci (Rapid Medical, Israel), to assist in the coiling of cerebral aneurysms. The Comaneci device confers the same benefits as balloon remodeling but without the risks of parent artery occlusion. This alleviates time pressure on the clinician, and could reduce the risk of parent artery thrombosis. Three patients were treated with the Comaneci device. Two patients had acute ruptured posterior communicating aneurysms and one patient was treated electively for a carotico-ophthalmic aneurysm. Excellent occlusion of all three aneurysms was obtained. One patient developed a distal middle cerebral artery clot, that was treated with intravenous aspirin, with minor neurological consequences. These early results show that the Comaneci device can be used to achieve good cerebral aneurysm occlusion. Vessel patency is maintained throughout the procedure with potential advantages over conventional balloon assisted coiling. PMID- 26138731 TI - Improved clinical outcome 3 months after endovascular treatment, including thrombectomy, in patients with acute ischemic stroke: a meta-analysis. AB - BACKGROUND AND PURPOSE: Intravenous thrombolysis with tissue plasminogen activator is standard treatment in acute stroke today. The benefit of endovascular treatment has been questioned. Recently, studies evaluating endovascular treatment and intravenous thrombolysis compared with intravenous thrombolysis alone, have reported improved outcome for the intervention group. The aim of this study was to perform a meta-analysis of randomized controlled trials comparing endovascular treatment in addition to intravenous thrombolysis with intravenous thrombolysis alone. METHODS: Databases were searched for eligible randomized controlled trials. The primary outcome was a functional neurological outcome after 90 days. A secondary outcome was severe disability and death. Data were pooled in the control and intervention groups, and OR was calculated on an intention to treat basis with 95% CIs. Outcome heterogeneity was evaluated with Cochrane's Q test (significance level cut-off value at <0.10) and I(2) (significance cut-off value >50%) with the Mantel-Haenszel method for dichotomous outcomes. A p value <0.05 was regarded as statistically significant. RESULTS: Six studies met the eligibility criteria, and data from 1569 patients were analyzed. A higher probability of a functional neurological outcome after 90 days was found for the intervention group (OR 2, 95% CI 2 to 3). There was a significantly higher probability of death and severe disability in the control group compared with the intervention group. CONCLUSIONS: Endovascular treatment in addition to intravenous thrombolysis for acute ischemic stroke leads to an improved clinical outcome after 3 months, compared with patients receiving intravenous thrombolysis alone. PMID- 26138732 TI - Physical characteristics of catheters used for subarachnoid drainage. AB - BACKGROUND: Cerebrospinal fluid diversion through lumbar drainage catheters is a routine procedure that is used in a variety of clinical applications. Fracture of catheters during insertion or removal may result in retained foreign bodies that may lead to patient morbidity with potential legal ramifications. Fracture resistance is an important component of drain selection. OBJECTIVE: To analyze catheter integrity to determine which commercially available catheters are most robust and resistant to fracture. METHODS: Physical properties of the commercially available drainage catheters that can be advanced through a Touhy needle were assessed using laboratory equipment and reported. Five types of catheter were analyzed for break load, tensile strength, extension at break, and shear strength. RESULTS AND CONCLUSIONS: Of the five types of catheter, the Arrow catheter showed the greatest resistance to fracture. Of the drainage catheters, the Codman catheter showed the greatest resistance to fracture. PMID- 26138733 TI - Cartilage Restoration of the Knee: A Systematic Review and Meta-analysis of Level 1 Studies. AB - BACKGROUND: Focal cartilage defects of the knee are a substantial cause of pain and disability in active patients. There has been an emergence of randomized controlled trials evaluating surgical techniques to manage such injuries, including marrow stimulation (MS), autologous chondrocyte implantation (ACI), and osteochondral autograft transfer (OAT). PURPOSE: A meta-analysis was conducted to determine if any single technique provides superior clinical results at intermediate follow-up. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched and supplemented with manual searches of PubMed and reference lists. Eligible studies consisted exclusively of randomized controlled trials comparing MS, ACI, or OAT techniques in patients with focal cartilage defects of the knee. The primary outcome of interest was function (Lysholm score, International Knee Documentation Committee score, Knee Osteoarthritis Outcome Score) and pain at 24 months postoperatively. A meta analysis using standardized mean differences was performed to provide a pooled estimate of effect comparing treatments. RESULTS: A total of 12 eligible randomized trials with a cumulative sample size of 765 patients (62% males) and a mean (+/-SD) lesion size of 3.9 +/- 1.3 cm(2) were included in this review. There were 5 trials comparing ACI with MS, 3 comparing ACI with OAT, and 3 evaluating different generations of ACI. In a pooled analysis comparing ACI with MS, there was no difference in outcomes at 24-month follow-up for function (standardized mean difference, 0.47 [95% CI, -0.19 to 1.13]; P = .16) or pain (standardized mean difference, -0.13 [95% CI, -0.39 to 0.13]; P = .33). The comparisons of ACI to OAT or between different generations of ACI were not amenable to pooled analysis. Overall, 5 of the 6 trials concluded that there was no significant difference in functional outcomes between ACI and OAT or between generations of ACI. CONCLUSION: There is no significant difference between MS, ACI, and OAT in improving function and pain at intermediate-term follow-up. Further randomized trials with long-term outcomes are warranted. PMID- 26138734 TI - Femoral and tibial graft tunnel parameters after transtibial, anteromedial portal, and outside-in single-bundle anterior cruciate ligament reconstruction. AB - BACKGROUND: Anatomic graft tunnel placement is recommended in anterior cruciate ligament (ACL) reconstruction to restore knee joint stability and function. Transtibial (TT), anteromedial portal (AMP), and outside-in (OI) retrograde drilling surgical techniques have been described for tibial and femoral bone tunnel preparation. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the bone tunnel parameters and compare the ability of 3 different surgical techniques to achieve placement of the ACL femoral and tibial bone tunnels at the center of the native ACL femoral and tibial attachment sites. The hypothesis was that tunnel placement using an AMP or OI technique would result in optimized tunnel parameters and more closely reconstruct the center of the native ACL femoral attachment site. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The study population consisted of 100 patients undergoing anatomic single-bundle ACL reconstruction using multiple-stranded hamstring tendon grafts. In group 1 (n = 36), the femoral tunnel was drilled using a TT surgical technique; in group 2 (n = 32), the femoral tunnel was drilled through an AMP; and in group 3 (n = 32), the femoral tunnel was created by use of an OI technique with retrograde drilling. Computed tomography (CT) scans were obtained postoperatively, and characteristics of femoral and tibial tunnel apertures were correlated to femoral and tibial measurement grid systems. The position of the resulting tibial and femoral bone tunnels for each group was compared with the center of the native ACL attachment sites. RESULTS: There were statistically significant differences (P < .05) for the ACL femoral tunnel between the 3 groups with respect to intercondylar height, total tunnel length, graft fixation length, tunnel axis, and tunnel entry angle. Statistically significant differences (P < .05) were found for the ACL tibial tunnel with respect to anteroposterior tunnel position and sagittal tunnel axis between the TT and both the OI and AMP techniques. The OI surgical technique produced more oblique and anatomically correct femoral tunnel apertures and longer femoral tunnel lengths compared with the AMP technique. Both AMP and OI techniques resulted in a more precise replication of intercondylar tunnel depth and height. There was no statistically significant difference for graft fixation length between the AMP and OI techniques. CONCLUSION: The AMP and OI surgical techniques were superior in positioning the ACL femoral tunnel at the center of the native ACL attachment site compared with the TT technique. An acceptable graft fixation length was obtained for all 3 surgical techniques. PMID- 26138735 TI - Vitamin D dosing for infectious and immune disorders. PMID- 26138736 TI - Research in progress--LungSEARCH: a randomised controlled trial of surveillance for the early detection of lung cancer in a high-risk group. AB - Low-dose CT screening for lung cancer is effective but expensive. Therefore, cheaper or more focused screening strategies may be required. LungSEARCH is a randomised prospective trial of 1568 high-risk individuals (ie, current or former moderate to heavy smokers with mild/moderate COPD) who undergo either annual sputum cytology/cytometry testing or no screening. Those with abnormal sputum then receive annual CT and fluorescent bronchoscopy for the remainder of 5 years, to identify early stage lung cancer. It is hoped that these simple initial tests could identify those requiring expensive CT scans, and the aim is to demonstrate a stage shift towards early stage cancers.Trial registration numbers ISRCTN: ISRCTN80745975, clinicaltrials.gov: NCT00512746. PMID- 26138737 TI - Is 50p a unit too much to ask? PMID- 26138738 TI - Measurement and explanation of socioeconomic inequality in catastrophic health care expenditure: evidence from the rural areas of Shaanxi Province. AB - BACKGROUND: Policy interventions have been taken to protect households from facing unpredictable economic changes that may cause catastrophe in China. This study aims to estimate the change of overall proportion of households incurring catastrophic health care expenditure (CHE) and its income-related inequality in the rural areas of Shaanxi Province from 2008 to 2013. METHODS: The data were drawn from the National Household Health Service Surveys of Shaanxi Province conducted in the years 2008 and 2013. In total, 3,217 households in 2008 and 13,085 households in 2013 were selected for analysis. A "Capacity to pay" approach was used to measure the incidence of CHE. The concentration index was employed to measure the extent of income-related inequality in CHE. A decomposition method, based on a logit model, was used to decompose the concentration index into its determining components. RESULTS: From 2008 to 2013, the overall proportion of households incurring CHE dropped from 17.19 % to 15.83 %, while conversely, the inequality in facing CHE strongly increased. The majority of observed inequalities in CHE were explained by household economic status and household size in 2013. In addition, the absence of commercial health insurance and having elderly members were also important contributors to inequality in CHE. CONCLUSIONS: Even though we used a conservative method to measure CHE, the overall proportion of households incurring CHE in Shaanxi Province is still considerably high in both years. Furthermore, there exists a strong pro-rich inequality of CHE in rural areas of Shaanxi Province. Our study suggests that narrowing the gap of household economic status, improving the anti risk capability of small scale households, establishing prepayment mechanisms in health insurance, strengthening the depth of reimbursement and subsidising vulnerable households in Shaanxi Province are helpful for both reducing the probability of incurring CHE and the pro-rich inequality in CHE. PMID- 26138739 TI - [Labial recurrent swelling revealing median congenital upper-lip fistula]. AB - Midline upper-lip fistulas are an extremely rare variant of congenital facial malformations. Less than 30 cases have been reported in the literature since 1970. We report the case of a 2 and a half-year-old girl presenting with a median congenital blind fistula of the upper lip, without any relation with the oral cavity. A recurrent swelling of the upper lip was the main symptom. Complete surgical excision of the cyst or of the fistulous tract must be obtained to avoid recurrence. PMID- 26138740 TI - Medical complications of anorexia nervosa and their treatments: an update on some critical aspects. AB - Anorexia nervosa has the highest mortality rate of any psychiatric disorder. Many of the deaths are attributable to medical complications which arise as the malnutrition and weight loss worsens. Every body system may be adversely affected by anorexia nervosa. Yet, remarkably, most of the medical complications of anorexia nervosa are treatable and reversible with optimal medical care, as part of a multidisciplinary team who are often involved in the care of these patients. Herein, we will describe the medical complications of anorexia nervosa and their treatments. PMID- 26138741 TI - Contemporary trends in urinary tract stone surgery, a regional perspective: Auckland, New Zealand. AB - BACKGROUND: The aim of the study is to assess the contemporary patterns of utilization of various therapeutic options for the management of nephrolithiasis in our tertiary referral institution in Auckland, New Zealand. METHODS: A retrospective audit was conducted for all urinary stone procedures between January 2007 and December 2013. Procedure-related information was collected for each year. All elective and emergency procedures were included. Data were collected on the elective waiting lists for each procedure. RESULTS: A total of 5512 stone-related cases were performed during the study period. Six hundred and fifty-three cases were performed in 2007 compared with 945 in 2013. Total number of percutaneous nephrolithotomy (PCNLs) performed, as well as the proportion of PCNL cases, demonstrated a significant decline from 84 (12.9%) in 2007 to 67 (7.1%) in 2013. While the annual numbers of extracorporeal shock wave lithotripsy (ESWLs) have increased, the percentage of ESWLs performed relative to total stone procedures has declined from 33% to 23% over the last 4 years of this audit. There has been a significant rise in the numbers of rigid and flexible ureteroscopies, with these now being the most utilized procedure. The number of patients awaiting elective procedures declined over the duration of this audit, with an associated improvement in meeting annual demand for treatment of nephrolithiasis from 78% in 2007 to 91% in 2013. CONCLUSIONS: A proportional decline in PCNL and ESWL utilization with a significant increase in flexible and rigid ureteroscopic procedures has been observed over this time and this pattern has been associated with improved adherence to surgical targets despite an increasing number of cases. PMID- 26138742 TI - Another Step Forward in Iron Chelation Therapy. PMID- 26138743 TI - Uroperitoneum in cattle: Ultrasonographic findings, diagnosis and treatment. AB - This review describes causes, clinical signs, metabolic changes in serum and peritoneal fluid, diagnosis and treatment of uroperitoneum. Rupture of the bladder or urachus is the most common cause of uroperitoneum. The main clinical sign is a pear-shaped enlargement of the abdomen accompanied by gradual deterioration in demeanour and appetite. Ultrasonography shows massive accumulation of anechoic abdominal fluid and organs suspended in the fluid. Bladder defects may be seen cystoscopically and the proximal part of a persistent urachus can be explored endoscopically. Abdominocentesis yields light yellow fluid. A peritoneal-to-serum creatinine concentration ratio of 2 or greater is diagnostic of uroperitoneum. Treatment consists of surgical repair of the defect. PMID- 26138744 TI - Increased utilization, verification, and clinical implications of immunocytochemistry: Experience in a northern New England hospital. AB - BACKGROUND: We report our experience in utilization, verification, and clinical implications of antibodies for use in diagnostic immunocytochemistry (ICC). METHODS: A computer search identified cytology cases utilizing ICC and corresponding surgical pathology material. Alcohol-fixed liquid based cytology (LBC) specimens were generated from surgical pathology bench specimens. ICC on LBC and immunohistochemistry on formalin fixed paraffin embedded tissue (FFPE) were performed in parallel for 71 commonly used antibodies. Cytology and corresponding surgical pathology reports were reviewed for all cases in which antibodies failed verification studies but had been used in the four years prior to implementation of our verification process. RESULTS: From 2007 to 2011, the number of cytology cases in which ICC was performed increased from 98 (or 5% of all non-Pap test/nonurine cytology cases in our laboratory) to 306 (or 15%). Verification studies revealed calretinin, CD5, c-kit/CD117, inhibin, napsin A, OCT 3/4, and PAX-5 to be nonreliable in LBC despite consistent immunoreactivity in concurrent IHC on surgical specimens. No antibodies were found to be immunoreactive on LBC but nonreactive on FFPE. No adverse clinical outcomes resulted from the use of nonverified antibodies. CONCLUSIONS: Utilization of ICC at our institution has increased dramatically in recent years. Our verification process confirmed reliability in the majority of antibodies, but did identify several inconsistent antibodies. Although, in our series, no adverse clinical outcomes resulted from preverification use of these inconsistent antibodies, we encourage other institutions to confirm reliability of antibodies prior to use for diagnostic ICC. PMID- 26138745 TI - Charge-sensitive fluorescent nanosensors created from nanodiamonds. AB - We show that fluorescent nanodiamonds (FNDs) are among the few types of nanosensors that enable direct optical reading of noncovalent molecular events. The unique sensing mechanism is based on switching between the negatively charged and neutral states of NV centers which is induced by the interaction of the FND surface with charged molecules. PMID- 26138746 TI - The Relationship Between Industry and Pain Societies, Part 1: Demystification and Legitimization of Continuing Medical Education. PMID- 26138747 TI - Genome-wide identification of differential methylation between primary and recurrent hepatocellular carcinomas. AB - A biomarker capable of clinically predicting hepatocellular carcinoma (HCC) recurrence has not previously been established. Here genome-wide differential methylation between primary and recurrent HCC cell lines (Hep-11 and Hep-12) from the same patient was characterized. The HCC samples from two independent cohorts, complete with follow-up data, were used to validate the feasibility of the selected methylation biomarkers in predicting HCC prognosis. A methylation array assay identified 30 candidate genes or intergenic-fragments with an absolute methylation fold-change >2.0 between these cell lines; 22 candidates were hypomethylated in Hep-12 cells relative to Hep-11 cells. Bisulfite sequencing confirmed these results. Most importantly, classification of tumors by LINE-2 methylation level was significantly associated with HCC recurrence in both cohorts (P < 0.02). Similarly, MAD1L1 and LINC00682 methylation levels also correlated with HCC recurrence. Survival analysis showed that a combined baseline LINE-2, MAD1L1, and LINC00682 methylation signature was significantly associated with short recurrence-free survival in patients from both cohorts. A synergic effect was observed between these markers on both recurrence-free survival (P < 0.010) and overall survival (P < 0.040). In conclusion, low levels of LINE-2, MAD1L1, and LINC00682 methylation were associated with recurrence and decreased overall survival in HCC patients. (c) 2015 Wiley Periodicals, Inc. PMID- 26138748 TI - Costs and Clinical Outcomes of Epilepsy Surgery in Children With Drug-Resistant Epilepsy. AB - PURPOSE: Approximately 20% of children with epilepsy are drug-resistant, incurring considerable costs. Epilepsy surgery has been shown to be an effective intervention in this population. This study provides an initial look at the costs associated with surgical management of children with drug-resistant epilepsy as compared with medical management alone. PROCEDURES: In a retrospective cohort study of children with drug-resistant epilepsy referred for possible surgical intervention, we compared direct costs of those treated surgically versus those offered surgery but managed medically instead. We also assessed the difference in seizure frequency between the two groups. FINDINGS: There were 94 total patients, 78 (83%) in the surgical group and 16 (17%) in the medical group. The median (25th-75th percentile) cost of the epilepsy surgery hospitalization was $118,400 ($101,900-$143,800). Total median annual follow-up costs, not including the cost of surgical hospitalization, were not significantly different between the two groups at 1- or 2-year follow-up. However, the surgical patients who were seizure free at 1-year follow-up, and those that remained seizure-free at 2-year follow up, had significantly lower costs compared with the medical group ($8000 versus $16,200, P = 0.04 and $4300 versus $7600, P = 0.05, respectively). The surgical group had significantly fewer seizures compared with the medical group at 1-year follow-up. CONCLUSIONS: Although epilepsy surgery is expensive and the overall costs of surgical and medical management are similar in the first 2 years, patients who achieved seizure freedom after surgery had lower costs compared with those treated medically. PMID- 26138749 TI - In search of the magic bullet: can liver inflammation and fibrosis be reversed with medications? AB - Recent clinical studies comprising patients successfully treated for viral hepatitis have shown that liver fibrogenesis may be reverted, even at later stages including during bridging fibrosis and cirrhosis. Intensive research has identified numerous potential novel targets in liver disease. Multiple innovative compounds have now entered clinical trials, mostly in non-alcoholic steatohepatitis (NASH) and NASH-associated cirrhosis due to their outstanding epidemiological relevance. In general, regression from liver fibrosis follows four major mechanistic principles: termination of chronic damage, shifting the cellular bias from inflammation to resolution, deactivation of myofibroblasts and direct matrix degradation. Obeying these principles, several promising approaches are currently evaluated, for example, targeting inflammatory macrophages via inhibition of chemokine CCL2, its receptor CCR2 or galectin-3, bone marrow derived cell transfer, or antibodies against matrix-stabilizing lysyl oxidase like-2. The ongoing trials will reveal which of the many potential targets prove to have clinical efficacy, bearing in mind that fibrosis reversibility is less likely to be achieved in humans than in animal models. PMID- 26138750 TI - Substrate-Tuned Catalysis of the Radical S-Adenosyl-L-Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis. AB - NosL is a radical S-adenosyl-L-methionine (SAM) enzyme that converts L-Trp to 3 methyl-2-indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2 amino-3-(benzofuran-3-yl)propanoic acid (ABPA), we clearly demonstrated that the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L-Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical-mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities. PMID- 26138751 TI - Long-term follow-up of two patients with oligocone trichromacy. AB - INTRODUCTION: Oligocone trichromacy (OT) is an uncommon cone dysfunction disorder, the mechanism of which remains poorly understood. OT has been thought to be non-progressive, but its long-term visual outcome has been seldom reported in the literature. Our aim was to present two OT patients followed at our institution over 18 years. MATERIALS AND METHODS: Complete ocular examination, color vision, visual fields, and full-field electroretinography (ERG) were performed at initial presentation and follow-up. Spectral-domain optical coherence tomography (OCT) was performed during follow-up when available at our institution. RESULTS: Initial ocular examination showed satisfactory visual acuities with normal fundus examination and near-to-normal color vision. However, computerized perimetry demonstrated a ring-shaped scotoma around fixation, and ERG showed a profound cone dysfunction. The discrepancy between preserved color vision and profound cone dysfunction leads to the diagnosis of OT. Subsequent follow-ups over 18 years showed subtle degradation of visual acuities along with progression of the myopia in both patients and slight worsening of color vision in one patient. Initial OCT revealed a focal interruption of the ellipsoid line along with decreased thickness of the perifoveal macula. Subsequent OCT imaging performed 2 years later did not show any macular changes. CONCLUSION: Although OT is known to be a non-progressive cone dysfunction, our results suggest that subtle degradation of the visual function might happen over time. PMID- 26138752 TI - Are a Double Duct Sign or Endoscopic Biopsies Reliable Predictors of Malignancy in Periampullary Lesions. AB - AIM: To determine the predictive value of a double duct sign (DDS) and endoscopic biopsies to differentiate invasive carcinoma from premalignant lesions. METHODS: Two hundred and forty one patients (mean age 65.8; male 55.6%) diagnosed with a periampullary lesion from January 1987 through March 2013 were reviewed retrospectively with regard to background characteristics, histology of endoscopic biopsy, diameter of both common bile duct (CBD) and main pancreatic duct (PD), bilirubin levels and final diagnosis. RESULTS: DDS predicted malignancy with 73% specificity and 72% sensitivity. Endoscopic biopsies predicted malignancy with 96% specificity, 71% sensitivity and a negative predictive value (NPV) of 51%. Multivariable logistic regression analysis showed that DDS is a significant predictor for the presence of malignancy with an odds ratio of 6.37 adjusted to age, gender and endoscopic biopsy. CONCLUSION: Although DDS is indicative of malignancy in periampullary lesions, its clinical use is limited, given the low sensitivity and specificity. The diagnostic value of endoscopic biopsies is also poor due to a low sensitivity and NPV. If a double duct sign is present, physicians must be aware of an increased possibility of a malignant underlying cause, even if the histopathological examination of the biopsies did not show invasive malignancy. PMID- 26138753 TI - What is the Role of HbA1c in Diabetic Hemodialysis Patients? AB - The definition of a good glycemic control in patients with diabetes mellitus on hemodialysis is far from settled. In the general population, hemoglobin A1c is highly correlated with the average glycemia of the last 8-12 weeks. However, in hemodialysis patients, the correlation of hbA1c with glycemia is weaker as it also reflects changes in hemoglobin characteristics and red blood cells half life. As expected, studies show that the association between HbA1c and outcomes in these patients differ from the general population. Therefore, the value of HbA1c in the treatment of hemodialysis patients has been questioned. Guidelines are generally cautious in their recommendations about possible targets of HbA1c in this population. Indeed, the risk of not treating hyperglycemia should be weighed against the particularly high risk of precipitating hypoglycemia in dialysis patients. In this review, a critical analysis of the current role of HbA1c in the care of hemodialysis patients is presented. PMID- 26138754 TI - Use of a formal consensus development technique to produce recommendations for improving the effectiveness of adult mental health multidisciplinary team meetings. AB - BACKGROUND: Multidisciplinary team (MDT) meetings are the core mechanism for delivering mental health care but it is unclear which models improve care quality. The aim of the study was to agree recommendations for improving the effectiveness of adult mental health MDT meetings, based on national guidance, research evidence and experiential insights from mental health and other medical specialties. METHODS: We established an expert panel of 16 health care professionals, policy-makers and patient representatives. Five panellists had experience in a range of adult mental health services, five in heart failure services and six in cancer services. Panellists privately rated 68 potential recommendations on a scale of one to nine, and re-rated them after panel discussion using the RAND/UCLA Appropriateness Method to determine consensus. RESULTS: We obtained agreement (median >= 7) and low variation in extent of agreement (Mean Absolute Deviation from Median of <=1.11) for 21 recommendations. These included the explicit agreement and auditing of MDT meeting objectives, and the documentation and monitoring of treatment plan implementation. CONCLUSIONS: Formal consensus development methods that involved learning across specialities led to feasible recommendations for improved MDT meeting effectiveness in a wide range of settings. Our findings may be used by adult mental health teams to reflect on their practice and facilitate improvement. In some other contexts, the recommendations will require modification. For example, in Child and Adolescent Mental Health Services, context-specific issues such as the role of carers should be taken into account. A limitation of the comparative approach adopted was that only five members of the panel of 16 experts were mental health specialists. PMID- 26138755 TI - Genome-wide microRNA screening reveals that the evolutionary conserved miR-9a regulates body growth by targeting sNPFR1/NPYR. AB - MicroRNAs (miRNAs) regulate many physiological processes including body growth. Insulin/IGF signalling is the primary regulator of animal body growth, but the extent to which miRNAs act in insulin-producing cells (IPCs) is unclear. Here we generate a UAS-miRNA library of Drosophila stocks and perform a genetic screen to identify miRNAs whose overexpression in the IPCs inhibits body growth in Drosophila. Through this screen, we identify miR-9a as an evolutionarily conserved regulator of insulin signalling and body growth. IPC-specific miR-9a overexpression reduces insulin signalling and body size. Of the predicted targets of miR-9a, we find that loss of miR-9a enhances the level of sNPFR1. We show via an in vitro binding assay that miR-9a binds to sNPFR1 mRNA in insect cells and to the mammalian orthologue NPY2R in rat insulinoma cells. These findings indicate that the conserved miR-9a regulates body growth by controlling sNPFR1/NPYR mediated modulation of insulin signalling. PMID- 26138756 TI - Characterization of Architectural Distortion in Mammograms Based on Texture Analysis Using Support Vector Machine Classifier with Clinical Evaluation. AB - Architecture distortion (AD) is an important and early sign of breast cancer, but due to its subtlety, it is often missed on the screening mammograms. The objective of this study is to create a quantitative approach for texture classification of AD based on various texture models, using support vector machine (SVM) classifier. The texture analysis has been done on the region of interest (ROI) selected from the original mammogram. A comprehensive analysis has been done on samples from three databases; out of which, two data sets are from the public domain, and the third data set is for clinical evaluation. The public domain databases are IRMA version of digital database for screening mammogram (DDSM) and Mammographic Image Analysis Society (MIAS). For clinical evaluation, the actual patient's database has been obtained from ACE Healthways, Diagnostic Centre Ludhiana, India. The significant finding of proposed study lies in appropriate selection of the size of ROIs. The experiments have been done on fixed size of ROIs as well as on the ground truth (variable size) ROIs. Best results pertain to an accuracy of 92.94 % obtained in case of DDSM database for fixed-size ROIs. In case of MIAS database, an accuracy of 95.34 % is achieved in AD versus non-AD (normal) cases for ground truth ROIs. Clinically, an accuracy of 88 % was achieved for ACE dataset. The results obtained in the present study are encouraging, as optimal result has been achieved for the proposed study in comparison with other related work in the same area. PMID- 26138758 TI - Cardiac contraction-induced GLUT4 translocation requires dual signaling input. AB - Contraction-induced translocation of glucose transporter type-4 (GLUT4) to the sarcolemma is essential to stimulate cardiac glucose uptake during increased energy demand. As such, this process is a target for therapeutic strategies aiming at increasing glucose uptake in insulin-resistant and/or diabetic hearts. AMP-activated protein kinase (AMPK) and its upstream kinases form part of a signaling axis essential for contraction-induced GLUT4 translocation. Recently, activation of protein kinase-D1 (PKD1) was also shown to be as obligatory for contraction-induced GLUT4 translocation in cardiac muscle. However, contraction induced PKD1 activation in this context occurs independently from AMPK signaling, suggesting that contraction-induced GLUT4 translocation requires the input of two separate signaling pathways. Necessity for dual input would more tightly couple GLUT4 translocation to stimuli that are inherent to cardiac contraction. PMID- 26138757 TI - SIRT3 regulates progression and development of diseases of aging. AB - The mitochondrial sirtuin SIRT3 is a protein deacylase that influences almost every major aspect of mitochondrial biology, including nutrient oxidation, ATP generation, reactive oxygen species (ROS) detoxification, mitochondrial dynamics, and the mitochondrial unfolded protein response (UPR). Interestingly, mice lacking SIRT3 (SIRT3KO), either spontaneously or when crossed with mouse models of disease, develop several diseases of aging at an accelerated pace, such as cancer, metabolic syndrome, cardiovascular disease, and neurodegenerative diseases, and, thus, might be a valuable model of accelerated aging. In this review, we discuss functions of SIRT3 in pathways involved in diseases of aging and how the lack of SIRT3 might accelerate the aging process. We also suggest that further studies on SIRT3 will help uncover important new pathways driving the aging process. PMID- 26138759 TI - Physiological relevance of plant 2-Cys peroxiredoxin overoxidation level and oligomerization status. AB - Peroxiredoxins are ubiquitous thioredoxin-dependent peroxidases presumed to display, upon environmental constraints, a chaperone function resulting from a redox-dependent conformational switch. In this work, using biochemical and genetic approaches, we aimed to unravel the factors regulating the redox status and the conformation of the plastidial 2-Cys peroxiredoxin (2-Cys PRX) in plants. In Arabidopsis, we show that in optimal growth conditions, the overoxidation level mainly depends on the availability of thioredoxin-related electron donors, but not on sulfiredoxin, the enzyme reducing the 2-Cys PRX overoxidized form. We also observed that upon various physiological temperature, osmotic and light stress conditions, the overoxidation level and oligomerization status of 2-Cys PRX can moderately vary depending on the constraint type. Further, no major change was noticed regarding protein conformation in water-stressed Arabidopsis, barley and potato plants, whereas species-dependent up- and down-variations in overoxidation were observed. In contrast, both 2-Cys PRX overoxidation and oligomerization were strongly induced during a severe oxidative stress generated by methyl viologen. From these data, revealing that the oligomerization status of plant 2-Cys PRX does not exhibit important variation and is not tightly linked to the protein redox status upon physiologically relevant environmental constraints, the possible in planta functions of 2-Cys PRX are discussed. PMID- 26138760 TI - Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment. AB - Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range. PMID- 26138761 TI - High Prevalence of Hypertension and End-Organ Damage Late After Coarctation Repair in Normal Arches. AB - BACKGROUND: To (1) determine the prevalence of hypertension late after coarctation repair in patients with normal-sized transverse arches, and (2) evaluate the potential for end-organ damage related to hypertension after coarctation repair. There are no studies specifically investigating end-organ damage and hypertension after coarctation repair using noninvasive techniques. METHODS: Eighty-two patients aged 10 years or greater with a coarctation repair and a normal-sized arch operated on between 1978 and 2010, underwent a transthoracic echocardiogram, 24-hour blood pressure (BP) monitoring, and retinal imaging. Median age at repair was 1 year (interquartile range, 0 to 6); 45% (37 of 82) were operated in the first year of life. RESULTS: After a follow-up of 24 +/- 7 years, 27% (22 of 82) and 50% (41 of 82) suffered resting hypertension and resting prehypertension, respectively. On 24-hour BP monitoring, 61% (49 of 80) and 21% (17 of 80) suffered hypertension and prehypertension, respectively. Arch reobstruction (echo gradient > 25 mm Hg) was present in only 15% (12 of 82), and in only 15% (7 of 47) with 24-hour hypertension. Resting hypertension was associated with a smaller central retinal artery equivalent (average width of arterioles) and central retinal vein equivalent (average width of venules) (p = 0.0006 and p = 0.003, respectively). Left ventricular hypertrophy on echocardiography was present in 63% (31 of 49) with 24-hour hypertension compared with only 42% (13 of 31) with normal 24-hour BP (p = 0.06). CONCLUSIONS: There is a high rate of hypertension late after coarctation repair, even in patients with unobstructed arches. The presence of retinal imaging abnormalities and left ventricular hypertrophy signals the presence of end-organ damage in this young adult population. Regular follow-up with 24-hour BP monitoring is warranted. PMID- 26138762 TI - Surgical Reconstruction of Peripheral Pulmonary Arteries: Strategies, Outcomes, and New Classification. AB - BACKGROUND: Pulmonary artery stenosis (PAS) is classified as central (types 1 and 2) and peripheral (type 3 affects proximal part of lobar arteries, type 4 affects proximal part of segmental arteries, and type 5 affects distal part of segmental arteries). In this study, we examine the outcomes of surgical reconstruction of peripheral PAS. METHODS: We reviewed 31 patients with peripheral PAS who underwent surgical repair. Median age was 30 months. Patients with intact ventricular septum (24 patients) presented with severe right ventricular dilation and dysfunction and mean right ventricular to left ventricular pressure (RVSP/LVSP) ratio was 0.96 +/- 0.25, 1.14 +/- 0.23, and 1.43 +/- 0.07 for types 3, 4, and 5, respectively (p = 0.03). Pulmonary artery reconstruction was achieved in single stage in 19 patients (61%). RESULTS: Six patients (19%) had type 3, 22 patients (71%) had type 4, and 3 patients (10%) had type 5. mean number of angioplasties per patient was 18 +/- 8. There was no early mortality. Mean postoperative RVSP/LVSP ratio decreased to 0.27 +/- 0.08, 0.36 +/- 0.05, and 0.96 +/- 0.06, for types 3, 4, and 5, respectively (p < 0.001). The median follow up was 48 months. Patients with type 3 and 4 showed marked improvement in functional status after surgery. Patients with type 5 showed clinical evidence of improved cardiac output despite modest decrease in RVSP. No surgical re intervention was needed, while balloon dilation was performed in 1 patient with type 5 lesions. CONCLUSIONS: Surgical reconstruction of diffuse peripheral PAS is feasible and associated with excellent hemodynamic and functional outcomes in patients where there is no involvement of the distal part of segmental arteries. PMID- 26138763 TI - Repair Type Influences Mode of Pulmonary Vein Stenosis in Total Anomalous Pulmonary Venous Drainage. AB - BACKGROUND: We hypothesized that primary sutureless (SL) repair of total anomalous pulmonary venous drainage (TAPVD) may have a lower incidence of postrepair pulmonary vein obstruction (PVO) and different modes of PVO compared with standard repair (SR). METHODS: One hundred ninety-five patients who underwent TAPVD repair (1990 to 2012) with the exception of congenital pulmonary vein stenosis, isomerism, and single-ventricle anomalies were included. Survival, reintervention, incidence, degree of PVO were compared between groups. The mode of PVO was expressed as central or peripheral. The Mann-Whitney test, Kaplan Meier analysis, and Cox regression were used. RESULTS: The SL group had more infracardiac or mixed TAPVD (p = 0.02) and preoperative PVO (p = 0.07). There were no differences between SR and SL groups in survival (5-year survival, 83.1% versus 82.5%, respectively; p = 0.73) and composite outcome (death, intervention, PVO, 5-year survival, 76.4% versus 80.7%, respectively; p = 0.225). The SL group had a lower incidence of PVO of moderate or greater degree (SR, 11.3% versus SL, 2.9%; p = 0.05) than the SR group, especially in the infracardiac and mixed TAPVD cohort (p = 0.011), with a lower pulmonary vein score (SR, 8 versus SL, 4; p = 0.01). The SL group had peripheral PVO exclusively (100%), whereas the SR group predominantly had central PVO (76.4%; p = 0.005). There was a trend toward less reoperation in the SL group (SR, 10.4% versus SL, 2.9%; p = 0.08). Survival after reoperation was comparable to primary TAPVD repair types as well as reoperation repair types. CONCLUSIONS: Primary SL appeared to be associated with a lower incidence and severity of PVO. The primary SL repair eliminated the risk of developing central PVO, although a relatively benign type of peripheral PVO could occur. PMID- 26138764 TI - Association Between Method of Cerebral Protection During Neonatal Aortic Arch Surgery and Attention Deficit/Hyperactivity Disorder. AB - BACKGROUND: Neonates undergoing repair of the aortic arch are at risk for adverse neurodevelopmental outcomes, including attention deficit/hyperactivity disorder (ADHD). The purpose of this study was to compare the effect of deep hypothermic circulatory arrest versus regional cerebral perfusion on the long-term outcome of ADHD. METHODS: This study is a cross-sectional observational study of ADHD in children who underwent neonatal aortic arch surgery. Attention Deficit/Hyperactivity Disorder-IV surveys were used to determine the prevalence of ADHD. Review of the medical records was performed to determine the primary method of cerebral protection and to extract related surgical variables. RESULTS: Surveys were sent to parents of 134 children, with 57 surveys completed (43%). The percentage of children classified as having ADHD was 44%. Children with a diagnosis of interrupted aortic arch had the highest prevalence of ADHD (85%). Multivariate analysis demonstrated that interrupted aortic arch was associated with an increased ADHD inattention score (p < 0.01), and a decreased Child Health Questionnaire-50 psychosocial score (p < 0.01). Low Child Health Questionnaire-50 psychosocial summary scores are associated with increased behavioral problems and are lower in patients with ADHD. CONCLUSIONS: Attention deficit/hyperactivity disorder is common after neonatal aortic arch surgery and may be primarily related to genetic predisposition. We found insufficient evidence to show that either deep hypothermic circulatory arrest or regional cerebral perfusion decreased the risk of ADHD. PMID- 26138765 TI - Intraoperative Echocardiography for Congenital Aortic Valve Repair: Predictors of Early Reoperation. AB - BACKGROUND: We sought to identify transesophageal echocardiography (TEE) predictors of early reoperation for recurrent aortic regurgitation (AR) after cardiopulmonary bypass (CPB) in patients undergoing repair for congenital aortic valve disease. METHODS: We analyzed post-CPB TEEs in patients with congenital aortic valve disease undergoing repair for predominant AR. Case patients underwent reoperation for recurrent AR within 2 years, whereas control patients were free from reoperation for more than 3 years. RESULTS: Case patients (n = 22; median time to reoperation 0.3 years) and control patients (n = 22; median freedom from reoperation >=4.4 years) were similar for demographic characteristics, aortic dimensions, and preoperative AR grade. Among post-CPB TEE variables, univariate logistic regression analysis identified shorter coaptation height (odds ratio [OR] for 1-mm increase 0.72, 95% confidence interval [CI]: 0.54 to 0.95; p = 0.02), decreased ratio of coaptation height to annulus diameter (OR for a 5% decrease 1.37, 95% CI: 1.06 to 1.77; p = 0.02), and increased percentage difference (%diff) between longest and shortest coaptation lengths in a short-axis view (OR for 10% increase 1.84, 95% CI: 1.15 to 2.92; p = 0.01) as risk factors for early reoperation for recurrent AR. Multivariable analysis identified %diff in short-axis coaptation lengths as the strongest post-CPB TEE predictor (area under receiver operator curve = 0.743). The sensitivity and specificity of a %diff of 50% were 0.45 and 0.91, whereas a %diff of 30% had a sensitivity of 0.75 and specificity of 0.67. CONCLUSIONS: Coaptation asymmetry, measured as increased %diff in short-axis coaptation lengths on post-CPB TEE, is associated with early reoperation for recurrent AR after congenital valve repair. PMID- 26138766 TI - Surgical Repair of Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collaterals With Absent Intrapericardial Pulmonary Arteries. AB - BACKGROUND: One anatomic variant of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals (PA/VSD/MAPCAs) is characterized by the absence of intrapericardial pulmonary arteries. This anatomy obviates the possibility of incorporating the pulmonary arteries for reconstruction or palliative procedures. The purpose of this study was to evaluate the surgical results in patients undergoing repair of PA/VSD/MAPCAs with absent pulmonary arteries. METHODS: This was a retrospective review of 35 patients who underwent surgical repair of PA/VSD/MAPCAs with absent pulmonary arteries between 2007 and 2014. The median age at the time of surgery was 3.4 months, and the median weight was 4.9 kg. All patients underwent unifocalization of MAPCAs, with an average of 3.5 +/- 1.4 MAPCAs per patient. RESULTS: Twenty-eight of the 35 patients (80%) underwent complete single-stage surgical repair, including unifocalization of MAPCAs, VSD closure, and right ventricle to pulmonary artery conduit. After complete repair, the average right ventricular to aortic pressure ratio was 0.33 +/- 0.07. There were no deaths in this subgroup. Seven patients (20%) were not deemed suitable candidates for VSD closure after their unifocalization procedure, and therefore underwent palliation with a central shunt. There was 1 operative death and 1 interim death. Three patients have subsequently undergone complete repair, and 2 are awaiting further evaluation and treatment. CONCLUSIONS: The majority of patients with PA/VSD/MAPCAs and absent pulmonary arteries can undergo complete single-stage repair with satisfactory postoperative hemodynamics. These results suggest that unifocalization of MAPCAs can provide a reasonable pulmonary vascular bed in the absence of intrapericardial pulmonary arteries. PMID- 26138768 TI - Results of Primary Repair Versus Shunt Palliation in Ductal Dependent Infants With Pulmonary Atresia and Ventricular Septal Defect. AB - BACKGROUND: The 2 management strategies of neonates born with ductal-dependent pulmonary atresia and ventricular septal defect (PAVSD) include single stage primary biventricular repair (BVR) or staged palliation with modified Blalock Taussig shunt (BTS) followed by second stage repair. Each approach is associated with specific benefits and drawbacks. We report outcomes of those 2 different strategies. METHODS: Between 2002 and 2012, 86 neonates with ductal-dependent PAVSD underwent surgery using primary repair (BVR group: n = 28, 33%) or shunt palliation (BTS group: n = 58, 67%). Early and late results were compared between the 2 groups. RESULTS: Median age was 6 days (interquartile range [IQR] 3-17) and median weight was 2.8 kg (IQR 2.5-3.3) with 27 patients (31%) 2.5 kg or less. Associated risk factors such as prematurity 36 weeks or less and genetic or extra cardiac malformations were present in 30% and 40% of patients, respectively. Hospital mortality occurred in 5 (5.8%) patients (1 [3.6%] for BVR versus 4 [6.9%] for BTS, p = 1.00). Overall 8-year survival was 76.5% (85.5% for BVR versus 72.2% for BTS, p = 0.189). On multivariable analysis, risk factors for mortality were genetic or extra-cardiac malformations (hazard ratio [HR], 2.8 (95% confidence interval [CI] 1.7% to 16.0%), p = 0.036) and postoperative extracorporeal membrane oxygenation (ECMO) (HR, 4.0 [95% CI, 1.1% to 14.4), p = 0.039). Freedom from right ventricular outflow tract reoperation after achievement of repair was 63.2% at 8 years (52.4% for BVR versus 70.2% for BTS, p = 0.170). On multivariable analysis, risk factors for reoperation were the use of conduit (HR, 8.7 [95% CI, 1.1% to 65.8%], p = 0.037) and prematurity (HR, 2.8 [95% CI, 1.1% to 7.2%], p = 0.028). CONCLUSIONS: Primary BVR of neonates with ductal-dependent PAVSD is associated with a trend for improved survival due to hospital and interstage mortality with the staged approach. Genetic or extra cardiac malformations are common and are associated with worse survival. PMID- 26138767 TI - Pediatric End-Stage Failing Hearts Demonstrate Increased Cardiac Stem Cells. AB - BACKGROUND: We sought to determine the location, expression, and characterization of cardiac stem cells (CSCs) in children with end-stage heart failure (ESHF). We hypothesized ESHF myocardium would contain an increased number of CSCs relative to age-matched healthy myocardium, and ESHF-derived CSCs would have diminished functional capacity as evidenced by reduced telomere length. METHODS: Tissue samples were obtained from the explanted hearts of children undergoing heart transplantation with ESHF, defined as New York Heart Association class III or IV and ejection fraction less than 0.20, and from age-matched congenital heart disease patients with normal myocardium. The expression profile of cardiac specific stem cell markers was determined using quantitative real time polymerase chain reaction and immunofluorescence. Cardiac stem cell growth reserve was assessed with telomere length. RESULTS: There were 15 ESHF and 15 age-matched congenital heart disease patients. End-stage heart failure myocardium demonstrated increased expression of c-kit(+) and islet-1(+) CSCs by 2.0- and 2.5 fold, respectively, compared with myocardium from congenital heart disease patients. There was no difference in expression of c-kit(+) CSCs with advancing age from infants to children in ESHF myocardium. The c-kit(+) CSCs isolated from ESHF patients demonstrated significantly reduced telomere length, suggesting a diminished functional capability in these cells (8.1 +/- 0.6 kbp versus 6.3 +/- 0.3 kbp; p = 0.015). CONCLUSIONS: End-stage heart failure myocardium demonstrated an age-independent increase in CSCs relative to healthy myocardium; however, these CSCs from ESHF patients may have diminished proliferative ability and reduced functionality as an autologous cell therapy candidate. Further investigation is necessary to determine the role of ESHF-derived CSCs within the myocardium. PMID- 26138769 TI - Impact of Patient Characteristics and Anatomy on Results of Norwood Operation for Hypoplastic Left Heart Syndrome. AB - BACKGROUND: We sought to review current-era experience with multistage palliation of neonates with hypoplastic left heart syndrome (HLHS) and to examine the patients' anatomic, and surgical risk factors influencing outcomes. METHODS: A retrospective review of 219 HLHS patients who underwent the Norwood operation from 2002 to 2012 was performed. Competing risks analyses modeled events after the Norwood operation (death/transplantation, progression to Glenn operation) and after the Glenn operation (death/transplantation progression to Fontan operation), and examined the risk factors affecting outcomes. RESULTS: Competing risks analysis showed that 1 year after the Norwood operation, 25% of patients had died and 75% had undergone the Glenn operation. Three years after the Glenn operation, 11% of patients had died or received transplantation, 48% had undergone the Fontan procedure, and 41% were alive awaiting the Fontan. The overall 8-year survival after the Norwood operation was 66%. The risk factors for mortality on multivariable models were postoperative requirement for extracorporeal membrane oxygenation (hazard ratio [HR]: 3.1 [1.8-5.4], p < 0.001), genetic/major extracardiac anomalies (HR: 2.7 [1.4-5.2], p = 0.002), unplanned cardiac reoperation (HR: 2.5 [1.3-5.0], p = 0.007), modified Blalock Taussig shunt use (HR: 2.4 [1.4-3.8], p < 0.001), and prematurity (HR: 1.9 [1.1 3.5], p = 0.030). Of note, anatomic factors such as HLHS subtype, ascending aorta diameter, restrictive atrial septum, and associated cardiac lesions did not affect outcomes (p > 0.10 each). CONCLUSIONS: This current single-institution experience demonstrates that patients' factors (ie, prematurity, low weight, genetic/extracardiac anomalies) continue to adversely affect survival. Conversely, surgical and perioperative management advances, along with the use of the right ventricle to pulmonary artery shunt, might have neutralized the effects of anatomic factors on survival. Technical imperfections requiring reoperations are associated with failure to progress through palliation stages and diminished survival. PMID- 26138770 TI - Mortality Risk and Pulmonary Function in Adults With Cystic Fibrosis at Time of Wait Listing for Lung Transplantation. AB - BACKGROUND: Lung transplantation (LTx) benefit for survival in cystic fibrosis (CF) patients placed on the wait list is not well studied. METHODS: To predict the relationship between initial forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and the hazard ratio (HR) associated with LTx in CF patients, the United Network for Organ Sharing database was queried from 2005 to 2006 for adult patients with CF. Survival was assessed from wait list entry time until death on wait list, death after LTx, or censoring. Multivariate Cox proportional hazards models were used to assess the effect of LTx. The first model estimated the HR of LTx with adjustment for FEV1 or FVC and other covariates, and the second model estimated the HR of LTx conditional on FEV1 or FVC at listing. RESULTS: Two hundred seventy-eight patients with CF were included in the cohort, and 277 were used for survival analysis. Lung transplantation reduced the risk for death controlling for FEV1 (HR, 0.601; 95% confidence interval, 0.375 to 0.964; p = 0.035) or controlling for FVC (HR, 0.547; 95% confidence interval, 0.336 to 0.889; p = 0.015). Interaction models found that the HR of LTx varied significantly across initial FEV1 and FVC, with the predicted LTx HR and 95% confidence interval being protective (HR < 1) at FEV1 of 25% or less and FVC of 40% or less, respectively. CONCLUSIONS: The benefit of LTx in adults with CF was significant at a lower baseline FEV1 than expected. A threshold for baseline FVC was established below which LTx was protective. PMID- 26138771 TI - Angiogenesis Biomarkers May Be Useful in the Management of Patients With Indeterminate Pulmonary Nodules. AB - BACKGROUND: Low-dose computed tomography (CT) lung cancer screening is known to have a high false positive rate. This study aims to survey biomarkers of angiogenesis for those capable of assigning clinical significance to indeterminate pulmonary nodules detected through CT imaging studies. METHODS: An institutional database and specimen repository was used to identify 193 patients with stage I non-small cell lung cancer (T1N0M0) and 110 patients with benign solitary pulmonary nodules detected by CT imaging studies. All specimens were evaluated in a blinded manner for 17 biomarkers of angiogenesis using multiplex immunoassays. Biomarker performance was calculated through the Mann-Whitney rank sum U test and a receiver operator characteristic analysis. These data were used to refine our previously reported multi-analyte classification panel, which was then externally validated against an independent patient cohort (n = 80). RESULTS: A total of 303 patients were screened for 17 biomarkers of angiogenesis. Median nodule size was 1.2 cm for benign cases and 1.8 cm for non-small cell lung cancer, whereas median smoking histories were 25 and 40 pack-years, respectively. Differences in serum concentrations of heparin-binding epidermal growth factor (HB-EGF), epidermal growth factor (EGF), vascular (V)EGF-A, VEGF-C, and VEGF-D were strongly significant (p <= 0.001) while follistatin, placental growth factor (PLGF), and bone morphogenic protein (BMP)-9 were significant (p <= 0.05) between patients with benign and malignant nodules. Our previously reported multi-analyte classification panel was refined to include interleukin (IL)-6, IL-10, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF)-alpha, insulin-like growth factor binding protein (IGFBP)-5, IGFBP-4, IGF-2, stromal cell-derived factor (SDF)-1(alpha+beta), HB-EGF, and HGF resulting in improved accuracy and a validated negative predictive value of 96.4%. CONCLUSIONS: Angiogenesis biomarkers may be useful in discriminating stage I NSCLC from benign pulmonary nodules. PMID- 26138773 TI - Different Impacts of Luminosity on Contrast Vision in Eyes with Transparent Optic Media and with Cataract Simulation. AB - OBJECTIVE: To evaluate the effect of luminous intensity on contrast vision under different ocular conditions. MATERIALS AND METHODS: Ninety eyes of 45 persons were included in this study as follows: 30 healthy eyes, 30 eyes with cataract simulation (using translucent glasses), and 30 myopic eyes. Contrast sensitivity was examined using 5 spatial frequencies (1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree) of sine wave contrast test optotypes for 4 light intensities (34, 68, 154, and 240 cd/m2). RESULTS: The mean linear contrast sensitivities averaged over the frequencies for each of the 4 light intensities were: healthy eyes: 59 +/- 11, 72 +/- 16, 79 +/- 23, and 80 +/- 19; myopic eyes: 52 +/- 13, 67 +/- 15, 73 +/- 21, and 75 +/- 18, and cataract simulation eyes: 15 +/- 7, 21 +/- 8.6, 28.7 +/- 13, and 28.6 +/- 13, respectively. The linear contrast sensitivities averaged over the light intensities for each of the 5 spatial frequencies were: healthy eyes: 78, 87, 117, 59, and 21; myopic eyes: 65, 84, 109, 54, and 29, and cataract simulation eyes: 37, 41, 28, 8, and 2. CONCLUSIONS: The light intensity level had a positive effect on the contrast sensitivity of the examined eyes, except for eyes with cataract simulation, where even the maximum light intensity did not improve the contrast vision. This indicates that patients with cataracts require increased contrast of text rather than brighter illumination to improve the quality of their vision. PMID- 26138772 TI - Predictors of treatment outcome in prosthetic joint infections treated with prosthesis retention. AB - PURPOSE: The reported success rates of debridement, antibiotics, and implant retention (DAIR) for prosthetic joint infections (PJIs) vary widely. Several risk factors have been described for treatment failure, but they vary between studies. The purpose of this study was to evaluate the predictors of DAIR failure in PJI treatment and to assess the efficacy of rifampin combined with ciprofloxacin versus rifampin combined with other antibiotics in staphylococcal PJIs. METHODS: Patients with PJI that underwent DAIR for the first time between February 2001 and August 2009 were identified retrospectively in the hospital's patient databases. A total of 113 PJI cases with early postoperative or acute haematogenous PJI were followed for up to two years from the start of treatment. RESULTS: In univariate analysis, variables significantly associated with treatment failure were acute haematogenous infections (p = 0.022), leucocyte count at admission > 10 * 10(9)/l (p < 0.01), pain in the joint (p < 0.01), and ineffective empirical antibiotics (p < 0.01). In a multivariate Cox model, leucocyte count > 10 * 10(9)/l and ineffective empirical antibiotics were significant risk factors for failure. Compared to rifampin-ciprofloxacin, the hazard ratio (HR) for treatment failure was significantly increased in the rifampin-other antibiotics group (HR 6.0, 95% CI 1.5-28.8, p = 0.014) and the group treated without rifampin (HR 14.4, 95% CI 3.1-66.9, p < 0.01). CONCLUSIONS: Rifampin-ciprofloxacin combination therapy was significantly more effective than rifampin combined with other antibiotics. Effective empirical antibiotics are essential for successful PJI treatment. PMID- 26138774 TI - Anti-alpha-glucosidase and Anti-dipeptidyl Peptidase-IV Activities of Extracts and Purified Compounds from Vitis thunbergii var. taiwaniana. AB - Ethanol extracts (Et) from the stem (S) and leaf (L) of Vitis thunbergii var. taiwaniana (VTT) were used to investigate yeast alpha-glucosidase and porcine kidney dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Both VTT-Et showed complete alpha-glucosidase inhibition at 0.1 mg/mL; VTT-S-Et and VTT-L-Et showed 26 and 11% DPP-IV inhibition, respectively, at 0.5 mg/mL. The VTT-Et interventions (20 and 50 mg/kg) resulted in improvements in impaired glucose tolerance of diet-induced obese rats. (+)-Hopeaphenol, (+)-vitisin A, and (-) vitisin B were isolated from the ethyl acetate fractions of S-Et and showed yeast alpha-glucosidase inhibition (IC50 = 18.30, 1.22, and 1.02 MUM) and porcine kidney DPP-IV inhibition (IC50 = 401, 90.75, and 15.3 MUM) compared to acarbose (6.39 mM) and sitagliptin (47.35 nM), respectively. Both (+)-vitisin A and (-) vitisin B showed mixed noncompetitive inhibition against yeast alpha-glucosidase and porcine kidney DPP-IV, respectively. These results proposed that VTT extracts might through inhibitions against alpha-glucosidase and DPP-IV improve the impaired glucose tolerance in diet-induced obese rats. PMID- 26138775 TI - Prunus persica var. platycarpa (Tabacchiera Peach): Bioactive Compounds and Antioxidant Activity of Pulp, Peel and Seed Ethanolic Extracts. AB - A comparative analysis of ethanol extracts from peel, pulp and seed of Prunus persica var. platycarpa (Tabacchiera peach) was done. The total phenol, flavonoid and carotenoid content as well as the antioxidant properties by using different in vitro assays (DPPH, ABTS, FRAP, Fe-chelating, beta-carotene bleaching test) were evaluated. Pulp extract was subjected to liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Gallic acid, protocatechuic acid, protocatechualdehyde, chlorogenic acid, p-coumaric acid, and ferulic acid were identified as main constituents. Pulp extract was characterized by the highest total phytonutrients content and exhibited the highest antioxidant activity in all in vitro assays (IC(50) values of 2.2 MUg/mL after 60 min of incubation by using beta-carotene bleaching test and 2.9 MUg/mL by using Fe-chelating assay). Overall, the obtained results suggest that P. persica var. platycarpa displays a good antioxidant activity and its consumption could be promoted. PMID- 26138776 TI - Reversal of diffuse patchy pattern in lung perfusion scan in a case of severe pulmonary arterial hypertension. AB - A diffuse patchy pattern in the perfusion scan of the lung is a hallmark of severe pulmonary arterial hypertension (PAH). However, the mechanisms of this unique pattern remain uncertain. We here present the case of a 19-year-old woman with severe PAH who demonstrated reversal of the diffuse patchy pattern with improvement of pulmonary blood flow within a month after upfront triple combination therapy. Our case is a first report showing reversibility of diffuse patchy pattern by a short-term treatment in severe PAH. These findings suggest the possibility that the mechanisms underlying the diffuse patchy pattern may involve reversible vasoconstriction in addition to remodeling of small pulmonary arteries. PMID- 26138777 TI - The effectiveness of tight glycemic control on decreasing surgical site infections and readmission rates in adult patients with diabetes undergoing cardiac surgery: A systematic review. AB - OBJECTIVE: A systematic review of the effects of tight glycemic control with a continuous insulin infusion to achieve blood glucose levels <= 200 mg/dL on surgical site infections and readmission rates in adult patients with diabetes after cardiac surgery. METHODS: A quantitative systematic review of the literature. Databases, including PubMed, CINAHL, EMBASE, and CENTRAL, were searched for relevant studies from database inception through August 2014. Randomized and quasi-experimental studies were included. RESULTS: A meta-analysis of ten studies demonstrated that glycemic control with a continuous insulin infusion to achieve blood glucose levels <= 200 mg/dL significantly reduced surgical site infection rates (odds ratio 0.35, 95% confidence interval 0.25 0.49; Z = 6.0, P < 0.00001) compared with standard diabetes management. CONCLUSIONS: Maintaining blood glucose levels <= 200 mg/dL with a continuous insulin infusion in all stages of the perioperative period in cardiac surgery patients with diabetes can reduce the incidence of surgical site infections. PMID- 26138778 TI - Increased gamma-H2AX and Rad51 DNA Repair Biomarker Expression in Human Cell Lines Resistant to the Chemotherapeutic Agents Nitrogen Mustard and Cisplatin. AB - Chemotherapeutic anticancer drugs mediate cytotoxicity by a number of mechanisms. However, alkylating agents which induce DNA interstrand crosslinks (ICL) are amongst the most effective anticancer agents and often form the mainstay of many anticancer therapies. The effectiveness of these drugs can be limited by the development of drug resistance in cancer cells and many studies have demonstrated that alterations in DNA repair kinetics are responsible for drug resistance. In this study we developed two cell lines resistant to the alkylating agents nitrogen mustard (HN2) and cisplatin (Pt). To determine if drug resistance was associated with enhanced ICL DNA repair we used immunocytochemistry and imaging flow cytometry to quantitate the number of gamma-H2AX and Rad51 foci in the nuclei of cells after drug exposure. gamma-H2AX was used to evaluate DNA strand breaks caused by repair incision nucleases and Rad51 was used to measure the activity of homologous recombination in the repair of ICL. In the drug-resistant derivative cell lines there was overall a significant increase in the number and persistence of both gamma-H2AX and Rad51 foci in the nuclei of cells over a 72 hour period, when compared to the non-resistant parental cell lines (ANOVA p < 0.0001). In a Pt-resistant ovarian cancer cell line (A2780cis(R)) a similar enhancement of DNA repair was observed when compared to the non-drug-resistant wild-type ovarian cancer cells (A2780) following exposure to HN2. Our data suggest that using DNA repair biomarkers to evaluate mechanisms of resistance in cancer cell lines and human tumours may be of experimental and clinical benefit. We concede, however, that examination of a larger population of cell lines and tumours is required to fully evaluate the validity of this approach. PMID- 26138779 TI - Introduction of time-based targets has improved the training environment for emergency medicine: No. PMID- 26138780 TI - Beta receptor-mediated modulation of the oddball P3 but not error-related ERP components in humans. AB - RATIONALE: The P3 is a ubiquitous component of stimulus-driven neural activity that can be observed in scalp electrophysiological recordings. Multiple lines of evidence suggest an important role for the noradrenergic system in the generation of the P3. However, pharmacological studies of the P3 using noradrenergic manipulations have so far been limited to agents that affect alpha2-receptor signaling. OBJECTIVES: The present study investigated whether beta-adrenergic receptors are involved in the generation of the P3 and the error positivity (Pe), a component of the event-related potential that is elicited by errors and that bears many similarities to the P3. METHODS: We used a double-blind, placebo controlled, crossover design in which we examined in human participants (N = 16) the effect of a single dose of propranolol (80 mg) on the amplitudes of the P3 observed in visual and auditory oddball tasks and the Pe observed in a flanker task. RESULTS: We found that P3s to auditory stimuli were increased in amplitude following treatment with propranolol. Propranolol also modulated the P3 to visual stimuli, but in a direction dependent on participants' level of trait anxiety: In participants with lower trait anxiety, propranolol resulted in a (non significant) decrease in P3 amplitudes; in participants with higher trait anxiety, propranolol significantly enhanced P3 amplitude. Propranolol did not modulate the amplitude of the Pe or behavioral measures of conflict/error-related performance adjustments. CONCLUSIONS: These results provide the first evidence for involvement of beta-adrenergic receptors in P3 generation. We speculate that propranolol affected the P3 through actions at beta2-receptors in the locus coeruleus. PMID- 26138781 TI - Automation, consolidation, and integration in autoimmune diagnostics. AB - Over the past two decades, we have witnessed an extraordinary change in autoimmune diagnostics, characterized by the progressive evolution of analytical technologies, the availability of new tests, and the explosive growth of molecular biology and proteomics. Aside from these huge improvements, organizational changes have also occurred which brought about a more modern vision of the autoimmune laboratory. The introduction of automation (for harmonization of testing, reduction of human error, reduction of handling steps, increase of productivity, decrease of turnaround time, improvement of safety), consolidation (combining different analytical technologies or strategies on one instrument or on one group of connected instruments) and integration (linking analytical instruments or group of instruments with pre- and post-analytical devices) opened a new era in immunodiagnostics. In this article, we review the most important changes that have occurred in autoimmune diagnostics and present some models related to the introduction of automation in the autoimmunology laboratory, such as automated indirect immunofluorescence and changes in the two step strategy for detection of autoantibodies; automated monoplex immunoassays and reduction of turnaround time; and automated multiplex immunoassays for autoantibody profiling. PMID- 26138783 TI - Correlation of clinical tools to determine activity of localized scleroderma in paediatric patients. PMID- 26138782 TI - Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases. AB - Common variable immunodeficiency is a primary immunodeficiency of unknown etiology characterized by low serum immunoglobulin G, a decreased ability to make specific antibodies, and variable T-cell defects. Approximately 10-30% of patients with common variable immunodeficiency develop clinical evidence of a diffuse parenchymal lung disease with a constellation of histopathologic findings termed granulomatous and lymphocytic interstitial lung disease. In this study, we characterized the histologic and immunohistochemical features in a series of 16 cases diagnosed by open lung biopsy. Peribronchiolar and interstitial lymphocytic infiltration, granulomatous inflammation, and organizing pneumonia were consistent features; interstitial fibrosis with architectural remodeling was also found in a subgroup of patients. By immunohistochemistry, a predominance of CD4+ T lymphocytes with variable numbers of CD8+ T cells and B cells was present, with a striking absence of FOXP3-positive T-regulatory cells. This heretofore unrecognized immunohistochemical finding needs further investigation for a potential role in the pathogenesis of the condition. The presence of interstitial fibrosis with or without architectural remodeling in a subset of patients also needs additional study, for effect on prognosis. PMID- 26138784 TI - Whatever happened to the doctor's opinion? PMID- 26138786 TI - Femoral neck fracture in advanced ankylosing spondylitis. PMID- 26138785 TI - Metabolite identification of seven active components of Huan-Nao-Yi-Cong-Fang in rat plasma using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry. AB - Huan-Nao-Yi-Cong-Fang (HNYCF) is a potential prescription in treating Alzheimer's disease. Seven constituents [ferulic acid (FA), 2,3,5,4'-tetrahydroxystilbene-2-O beta-d-glucoside (THSG), berberine hydrochloride (BHCl), emodin, ginsenoside Rg1 (Rg1), ginsenoside Re (Re) and ginsenoside Rb1 (Rb1)] have been used as quality chemical markers of HNYCF owing to their biological significance and high contents in crude plant materials. This study explored the metabolites of the seven bioactive components in rat plasma to give useful data for further study of the action mechanism of HNYCF. LC/MS-IT-TOF was used to simultaneously characterize the metabolites of the seven components. Using the combination of MetID Solution 1.0 software and accurate mass measurements, the metabolites of HNYCF were reliably characterized. Their structures were elucidated based on the accurate MS(2) spectra and comparisons of their changes in accurate molecular masses and fragment ions with those of parent compounds. A total of five parent active compounds (BHCl, emodin, Rg1, Rb1 and Re) and 10 metabolites were found from the rat plasma 2 h after oral administration of HNYCF dosage, of which two metabolites of emodin were observed for the first time. The proposed metabolic pathways of the bioactive components in the rat plasma are helpful for further studies on the pharmacokinetics and real active compound forms of this drug. PMID- 26138787 TI - Promoting metastasis: neutrophils and T cells join forces. AB - The role neutrophils play in cancer is a matter of debate as both pro- and anti tumor functions have been documented. In a recent publication in Nature, Coffelt et al. identify a new mechanism where neutrophils and T cells cooperate to generate metastasis-supporting immune suppression. PMID- 26138788 TI - Reply to: Obesity is an important health problem in survivors of pediatric acute lymphoblastic leukemia. PMID- 26138789 TI - Metal-organic fireworks: MOFs as integrated structural scaffolds for pyrotechnic materials. AB - A new approach to formulating pyrotechnic materials is presented whereby constituent ingredients are bound together in a solid-state lattice. This reduces the batch inconsistencies arising from the traditional approach of combining powders by ensuring the key ingredients are 'mixed' in appropriate quantities and are in intimate contact. Further benefits of these types of material are increased safety levels as well as simpler logistics, storage and manufacture. A systematic series of new frameworks comprising fuel and oxidiser agents (group 1 and 2 metal nodes & terephthalic acid derivatives as linkers) has been synthesised and structurally characterised. These new materials have been assessed for pyrotechnic effect by calorimetry and burn tests. Results indicate that these materials exhibit the desired pyrotechnic material properties and the effect can be correlated to the dimensionality of the structure. A new approach to formulating pyrotechnic materials is proposed whereby constituent ingredients are bound together in a solid-state lattice. A series of Metal-organic framework frameworks comprising fuel and oxidiser agents exhibits the desired properties of a pyrotechnic material and this effect is correlated to the dimensionality of the structure. PMID- 26138790 TI - Evaluation of right ventricular function in fetal hypoplastic left heart syndrome by color tissue Doppler imaging. AB - OBJECTIVE: Postnatal outcome of fetuses with hypoplastic left heart syndrome (HLHS) is determined mainly by right ventricular function. Our study examines whether there are differences in right ventricular function during gestation of fetuses with HLHS compared with healthy fetuses. METHODS: A prospective study was conducted including 20 fetuses with HLHS and 20 gestational age-matched controls. Peak systolic and diastolic right ventricular free wall velocities were assessed using color tissue Doppler imaging (c-TDI). Subsequently, isovolumic time intervals, ejection time (ET'), E'/A' ratio and tissue Doppler-derived myocardial performance index (MPI') were calculated. Possible changes to c-TDI indices during the course of pregnancy in both the HLHS group and the control group were investigated. RESULTS: Examination of right ventricular function revealed significantly lower E' velocities (13.6 vs 21.0 cm/s; P = 0.017) and E'/A' ratios (0.55 vs 0.76; P = 0.012) and prolonged isovolumic contraction time (ICT') (57.0 vs 45.7 ms; P = 0.008) in the HLHS group compared with healthy fetuses. Furthermore, isovolumic relaxation time and MPI' increased significantly with gestational age in HLHS fetuses but not in controls. Values for systolic and diastolic peak velocities (E', A', S'), ET' and ICT' did not change significantly during gestation in either group. CONCLUSION: Right ventricular function in HLHS is altered as early as in fetal life, well before palliative surgery is performed. Future research should provide further insight into ventricular remodeling during gestation in cases of HLHS. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26138792 TI - Myotonic dystrophy 2 manifesting with non-alcoholic and non-hepatitic liver cirrhosis. AB - OBJECTIVE: Though the liver is frequently affected in myotonic dystrophy type 1 and 2 (DM1, DM2), non-alcoholic and non-hepatitic liver cirrhosis have not been reported as a manifestation of DM2. CLINICAL PRESENTATION AND INTERVENTION: In a 52-year-old Caucasian male with DM2, the disease manifested as myopathy, mild myotonia, cataract, diabetes, erectile dysfunction, gastrointestinal dysmotility, dysarthria, mild myocardial thickening and non-alcoholic and non-hepatitic liver cirrhosis with portal hypertension and oesophageal varicosities since age 48 years. His 69-year-old sister, who carried a CCTG expansion of >300 in intron 1 of the CNBP/ZNF9 gene, also manifested in the liver with hyperbilirubinaemia, hepatopathy and hyperlipidaemia since age 48 years. Liver cirrhosis in the index patient was complicated by hyperamonemia, hepatic encephalopathy and flapping tremor. CONCLUSION: Rarely, DM2 may also manifest in the liver with elevated transaminases, steatosis or non-alcoholic, non-hepatitic liver cirrhosis with its common complications. In patients with cryptogenic non-alcoholic, non-hepatitic liver cirrhosis or cataract before age 50 years, DM2 should be excluded. PMID- 26138791 TI - A Novel High-Resolution and Sensitivity-Enhanced Three-Dimensional Solid-State NMR Experiment Under Ultrafast Magic Angle Spinning Conditions. AB - Although magic angle spinning (MAS) solid-state NMR is a powerful technique to obtain atomic-resolution insights into the structure and dynamics of a variety of chemical and biological solids, poor sensitivity has severely limited its applications. In this study, we demonstrate an approach that suitably combines proton-detection, ultrafast-MAS and multiple frequency dimensions to overcome this limitation. With the utilization of proton-proton dipolar recoupling and double quantum (DQ) coherence excitation/reconversion radio-frequency pulses, very high-resolution proton-based 3D NMR spectra that correlate single-quantum (SQ), DQ and SQ coherences of biological solids have been obtained successfully for the first time. The proposed technique requires a very small amount of sample and does not need multiple radio-frequency (RF) channels. It also reveals information about the proximity between a spin and a certain other dipolar coupled pair of spins in addition to regular SQ/DQ and SQ/SQ correlations. Although (1)H spectral resolution is still limited for densely proton-coupled systems, the 3D technique is valuable to study dilute proton systems, such as zeolites, small molecules, or deuterated samples. We also believe that this new methodology will aid in the design of a plethora of multidimensional NMR techniques and enable high-throughput investigation of an exciting class of solids at atomic-level resolution. PMID- 26138793 TI - Possible role of bacteria in the degradation of macro algae Desmarestia anceps Montagne (Phaeophyceae) in Antarctic marine waters. PMID- 26138794 TI - The center for causal discovery of biomedical knowledge from big data. AB - The Big Data to Knowledge (BD2K) Center for Causal Discovery is developing and disseminating an integrated set of open source tools that support causal modeling and discovery of biomedical knowledge from large and complex biomedical datasets. The Center integrates teams of biomedical and data scientists focused on the refinement of existing and the development of new constraint-based and Bayesian algorithms based on causal Bayesian networks, the optimization of software for efficient operation in a supercomputing environment, and the testing of algorithms and software developed using real data from 3 representative driving biomedical projects: cancer driver mutations, lung disease, and the functional connectome of the human brain. Associated training activities provide both biomedical and data scientists with the knowledge and skills needed to apply and extend these tools. Collaborative activities with the BD2K Consortium further advance causal discovery tools and integrate tools and resources developed by other centers. PMID- 26138796 TI - Men's use of networks to manage communication tensions related to a potential diagnosis of prostate cancer. AB - PURPOSE: This study used relational dialectics theory to explore the communication tensions experienced by men who were on a prostate biopsy waiting list and how they managed these tensions using their communication networks. METHOD: The study utilised dialectical analysis of 36 semi-structured interviews conducted from July to September 2012 in a city in the North Island of New Zealand. RESULTS: Dialectical analysis revealed men experienced four tensions; a) obligation to disclose/autonomy not to disclose; b) confident to help others/vulnerable and needing help from others; c) accept support/not accept support and d) desire for normality/need to tolerate uncertainty. These tensions were predominantly managed by vacillation. Specifically, the men used their communication network to select one pole with some people and the other pole with others to maintain balance between the poles of the dialectical tensions. CONCLUSIONS: Health care professionals can help men in this situation by having a conversation about disclosure and support prior to them being diagnosed, educating men to reframe or connect as a more effective form of tension management, and linking men who have small or ineffective networks to other resources such as social support networks to facilitate tension management. PMID- 26138795 TI - Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys. AB - Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17 to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID- 26138797 TI - The role of the cervical spine in post-concussion syndrome. AB - While much is known regarding the pathophysiology surrounding concussion injuries in the acute phase, there is little evidence to support many of the theorized etiologies to post-concussion syndrome (PCS); the chronic phase of concussion occurring in ~ 10-15% of concussed patients. This paper reviews the existing literature surrounding the numerous proposed theories of PCS and introduces another potential, and very treatable, cause of this chronic condition; cervical spine dysfunction due to concomitant whiplash-type injury. We also discuss a short case-series of five patients with diagnosed PCS having very favorable outcomes following various treatment and rehabilitative techniques aimed at restoring cervical spine function. PMID- 26138798 TI - Smoking-related idiopathic interstitial pneumonia: A review. AB - For many years, cigarette smoking has been considered as the leading cause of chronic obstructive pulmonary disease and lung cancer. Recently, however, it has also been associated with the development of diffuse interstitial lung diseases. In the latest classification of the major idiopathic interstitial pneumonias (IIP), the term smoking-related IIP has been introduced, including two entities, namely desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis interstitial lung disease (RB-ILD). Other entities in which smoking has a definite or suggested role include pulmonary Langerhan's cell histiocytosis, smoking-related interstitial fibrosis, combined pulmonary fibrosis and emphysema syndrome and idiopathic pulmonary fibrosis. In this review, we will focus on the mechanisms of smoking-related lung damage and on the clinical aspects of these disorders with the exception of idiopathic pulmonary fibrosis, which will be reviewed elsewhere in this review series. PMID- 26138799 TI - Chronic hepatitis B: Are we close to a cure? AB - Approximately 300 million people worldwide are persistently infected with the hepatitis B virus and are at risk of developing hepatocellular carcinoma and liver cirrhosis, which can progress to end-stage liver disease. Despite the effectiveness of the current vaccination policy, the prevalence of the disease remains high, and the burden for health services is considerable. The currently available antiviral strategies are either poorly effective or only effective for non-curative suppression of viral replication. Recent efforts have been focused on improving the cure rate for chronic hepatitis B and developing strategies to eliminate infected cells. Several approaches are under evaluation, and these include targeting the virus at different stages of its life cycle and boosting the antiviral immune response. This article reviews these latest approaches and comments on their feasibility and potential translation into clinical applications. PMID- 26138800 TI - PITER: An ongoing nationwide study on the real-life impact of direct acting antiviral based treatment for chronic hepatitis C in Italy. PMID- 26138801 TI - Noninvasive Mechanical Ventilation in Stable Hypercapnic Chronic Obstructive Pulmonary Disease: Is Restful Sleep a Suitable Distinctive Parameter? PMID- 26138802 TI - Experience-related reorganization of giant synapses in the lateral complex: Potential role in plasticity of the sky-compass pathway in the desert ant Cataglyphis fortis. AB - Cataglyphis desert ants undergo an age-related polyethism from interior workers to relatively short-lived foragers with remarkable visual navigation capabilities, predominantly achieved by path integration using a polarized skylight-based sun compass and a stride-integrating odometer. Behavioral and physiological experiments revealed that the polarization (POL) pattern is processed via specialized UV-photoreceptors in the dorsal rim area of the compound eye and POL sensitive optic lobe neurons. Further information about the neuronal substrate for processing of POL information in the ant brain has remained elusive. This work focuses on the lateral complex (LX), known as an important relay station in the insect sky-compass pathway. Neuroanatomical results in Cataglyphis fortis show that LX giant synapses (GS) connect large presynaptic terminals from anterior optic tubercle neurons with postsynaptic GABAergic profiles of tangential neurons innervating the ellipsoid body of the central complex. At the ultrastructural level, the cup-shaped presynaptic structures comprise many active zones contacting numerous small postsynaptic profiles. Three-dimensional quantification demonstrated a significantly higher number of GS (~ 13%) in foragers compared with interior workers. Light exposure, as opposed to age, was necessary and sufficient to trigger a similar increase in GS numbers. Furthermore, the increase in GS numbers was sensitive to the exclusion of UV light. As previous experiments have demonstrated the importance of the UV spectrum for sky-compass navigation in Cataglyphis, we conclude that plasticity in LX GS may reflect processes involved in the initial calibration of sky-compass neuronal circuits during orientation walks preceding active foraging. PMID- 26138803 TI - Appreciation of the research supervisory relationship by postgraduate nursing students. AB - INTRODUCTION: The quality of the relationship between postgraduate students and their supervisors often determines the progress of the students. BACKGROUND: Successful supervision according to students is associated with the expertise of the supervisors and their willingness to share their knowledge with their students. On the other hand, supervisors expect their students to be able to work independently to a large extent. Contradictory expectations of supervisors and postgraduate students can cause delays in the progress of students. AIM: The aim of this study was to explore and describe the aspects of the supervisory relationship that postgraduate students in nursing science at a selected university in South Africa appreciate. METHOD: A qualitative research design with an appreciative inquiry approach was used and 18 students under the guidance of an independent facilitator provided the data during group interviews. FINDINGS AND DISCUSSION: Specific personal and professional qualities of the supervisors contribute to a valued supervisory relationship. Regarding personal qualities, the supervisors should show their understanding of the unique circumstances of the students in challenging times. Supervisors should also be expert researchers. The valued relationship refers to an open and trusting relationship between the students and the supervisors. CONCLUSION: The students' appreciation of the research supervisory relationship contributes to the understanding of the expectations of postgraduate students regarding the support that they need to become scholars in an academic discipline. IMPLICATIONS FOR NURSING AND HEALTH POLICY: There is a need for continuing professional development of supervisors to sensitize them about the expectations of the students. PMID- 26138804 TI - Do We Really Want a Future as Qualitative Psychologists? AB - In this article I pick up some threads from the contributions in the previous special issue of IPSB dedicated to the future of qualitative psychology, and elaborate on them around two main points. The first is the status of qualitative psychology as a social and institutional category; the second is what we mean by experience. As concerns the first point, I argue that using the label of qualitative psychology may separate us from the rest of psychology, also creating a false impression of homogeneity among qualitative approaches and a false opposition with quantitative methods. Implications for teaching as well as research are discussed. The second issue has to do with experience as the object of qualitative psychology investigations. I propose three ways of formulating experience in research which would prevent naive assumptions about accessing it directly through language. These are 1) experience as experience of the researcher, 2) experience as situated intersubjectivity, and 3) experience as expression. I discuss how being clearer about definitions of experience and going towards engaged forms of research could safeguard the integrity of both researcher and participants. PMID- 26138805 TI - Effects of oxygen on light activation in covalent adaptable network polymers. AB - Light activated polymers are a novel group of active materials that deform when irradiated with light at specific wavelengths. This paper focuses on the understanding and evaluation of light activated covalent adaptable networks formed by radical polymerization reactions, which have potential applications as novel actuators, surface patterning, and light-induced bending and folding. In these polymer networks, free radicals are generated upon light irradiation and lead to evolution of the polymer network structure through bond exchange reactions. It is well known that oxygen is an important inhibitor in radical based chemistry as oxygen reacts with free radicals and renders them as inactive species towards further propagation and reaction. However, it is unclear how radical depletion by oxygen may affect the light-induced actuation. This paper studies the effects of oxygen on both stress relaxation and bending actuation. Light induced stress relaxation experiments are conducted in an environmental chamber where the concentration of oxygen is controlled by the nitrogen flow. A constitutive model that considers oxygen diffusion, radical termination due to oxygen, and the polymer network evolution is developed and used to study the stress relaxation and bending, and the model predictions agree well with experiments. Parametric studies are conducted to identify the situations where the effects of oxygen are negligible and other conditions where they must be considered. PMID- 26138806 TI - Internal medicine progress note writing attitudes and practices in an electronic health record. AB - BACKGROUND: The electronic health record (EHR) has been viewed with both praise and skepticism. Multiple editorials have expressed concerns that EHR implementation and "efficiency tools" such as copy forward and auto population have resulted in a decrement in note accuracy, relevance, and critical thinking. OBJECTIVE: To evaluate the perceptions of internal medicine housestaff and attendings on inpatient progress note quality at 4 academic institutions after the implementation of an EHR. DESIGN: Cross-sectional survey. MEASUREMENTS: We developed surveys that assessed housestaff and attendings opinion of current progress note quality, the impact of the EHR on quality, and the purposes of a progress note. RESULTS: We received 99 completed surveys from interns (66%), 155 from residents (49%), and 153 from attendings (70%) across 4 institutions. The majority of housestaff responded that the quality of notes was "unchanged" or "better" following the implementation of an EHR, whereas attendings believed note quality was "unchanged" or "worse." Attendings' perceptions of housestaff notes were significantly lower than housestaff perceptions of their own notes across all domains. With regard to the effect of copy forward and autopopulation, the majority of housestaff viewed these to be "neutral" or "somewhat positive," whereas attendings viewed these as "neutral" or "somewhat negative." Housestaff and attendings had nearly perfect agreement regarding the purpose of the progress note. CONCLUSIONS: Attendings and housestaff disagree on the current quality of progress notes and the impact of an EHR on note quality, but agree on the purpose of a progress note. PMID- 26138807 TI - Electronic and optical properties of pristine and boron-nitrogen doped graphyne nanotubes. AB - First principle calculations with generalized gradient approximation were carried out to analyse the electronic and optical properties of armchair and zigzag graphyne nanotubes (GNTs). The possible application of these NTs in optoelectronic devices was also investigated. The GNTs were doped with boron (B) and nitrogen (N) atoms and the resulting band gap tuning was studied with respect to the B/N substitution site and increasing diameter of the NTs. The basis of this variation was examined using the partial density of states and crystal orbital Hamilton population analysis. A decreasing trend in the optical response was seen with an increase in the diameter of the NTs. The reported systems showed anisotropic behaviour in the low-energy region. The origin of the optical responses was monitored from the infrared to the UV region depending on the doping site of the B/N. As a result of the large band gap, low reflectivity and low refractive index, B/N GNTs have been established as a suitable system for novel optoelectronic devices. The strong absorption peaks in the UV region mean that they are a good choice for use in UV light protection. PMID- 26138808 TI - Keratinized Gingiva Height Increases After Alveolar Corticotomy and Augmentation Bone Grafting. AB - BACKGROUND: The aim of the present study is to compare the keratinized gingival tissue (KT) height labial to the mandibular incisors after active orthodontic treatment (AOT) with and without alveolar corticotomy and bone grafting. METHODS: Two orthodontically treated groups of 35 patients each, with (Cort) and without (Conv) alveolar decortication and augmentation bone grafting, are matched in this case-control study for sample size, sex, mandibular premolar extractions, pretreatment age, post-treatment observation period, and pretreatment KT height. Standardized digital frontal occlusion photographs taken before and at least 1 year after AOT were adjusted to 96 dots per inch and measured with image analysis software for vertical KT height labial to each mandibular incisor. RESULTS: An average of 1.5 years after completion of AOT, KT height had increased significantly by 0.78 mm (P < 0.001) in the Cort group and decreased 0.38 mm (P = 0.002) in the Conv group; a 1.28-mm KT height gain was demonstrated in the subgroup representing the lowest half of Cort KT height at pretreatment. Mandibular incisor inclination and prominence explained neither the decrease in KT height in Conv nor the KT height gain in Cort. CONCLUSIONS: Orthodontic therapy combined with alveolar decortication and augmentation bone grafting resulted in a significant increase in KT height. Although KT height surrounding the dentition has been devalued by evidence-based studies, the value-added protection of KT height increase after decortication and augmentation bone grafting offsets the concerns of orthodontic proclination or expanding mandibular incisors facially. PMID- 26138809 TI - Can clock drawing differentiate Alzheimer's disease from other dementias? AB - BACKGROUND: Studies have shown the clock-drawing test (CDT) to be a useful screening test that differentiates between normal, elderly populations, and those diagnosed with dementia. However, the results of studies which have looked at the utility of the CDT to help differentiate Alzheimer's disease (AD) from other dementias have been conflicting. The purpose of this study was to explore the utility of the CDT in discriminating between patients with AD and other types of dementia. METHODS: A review was conducted using MEDLINE, PsycINFO, and Embase. Search terms included clock drawing or CLOX and dementia or Parkinson's Disease or AD or dementia with Lewy bodies (DLB) or vascular dementia (VaD). RESULTS: Twenty studies were included. In most of the studies, no significant differences were found in quantitative CDT scores between AD and VaD, DLB, and Parkinson's disease dementia (PDD) patients. However, frontotemporal dementia (FTD) patients consistently scored higher on the CDT than AD patients. Qualitative analyses of errors differentiated AD from other types of dementia. CONCLUSIONS: Overall, the CDT score may be useful in distinguishing between AD and FTD patients, but shows limited value in differentiating between AD and VaD, DLB, and PDD. Qualitative analysis of the type of CDT errors may be a useful adjunct in the differential diagnosis of the types of dementias. PMID- 26138811 TI - Bariatric surgery is linked to more diabetes remission than lifestyle intervention alone, study finds. PMID- 26138810 TI - The Association of FTO SNP rs9939609 with Weight Gain at University. AB - AIM: We tested the hypothesis that the obesity-associated FTO SNP rs9939609 would be associated with clinically significant weight gain (>= 5% of initial body weight) in the first year of university; a time identified as high risk for weight gain. METHODS: We collected anthropometric data from university students (n = 1,411, mean age: 22.4 +/- 2.5 years, 49.1% male) at the beginning and end of the academic year. DNA was analysed for FTO rs9939609. Associations of FTO genotype with BMI at baseline were analysed using ANCOVA, and with risk of 5% weight gain over follow-up with logistic regression; both analyses adjusting for age and sex. The alpha level was reduced to 0.0125 to account for multiple testing. RESULTS: Using an additive model, FTO status was not associated with higher BMI at baseline (22.2 vs. 21.9 kg/m2, p = 0.059). Dropout was high but unrelated to genotype. Among the 310 (21.9%) completing follow-up, those with AT genotypes had twice the odds of >= 5% weight gain compared with TTs (OR = 2.05, 95% CI = 1.05-4.01, p = 0.036), but this was no longer significant after Bonferroni correction. There was a trend for AA carriers for >= 5% weight gain compared with TT carriers (p = 0.089), but sample size was small. CONCLUSION: This study provides nominal evidence for the genetic susceptibility hypothesis, but findings need to be replicated. PMID- 26138812 TI - Assessment of a quantitative 5' nuclease real-time polymerase chain reaction using the nicotinamide adenine dinucleotide dehydrogenase gamma subunit (nuoG) for Bartonella species in domiciled and stray cats in Brazil. AB - OBJECTIVES: The objective of this study was to develop a quantitative 5' nuclease real-time polymerase chain reaction (PCR) assay to diagnose infections caused by Bartonella species. METHODS: Between January and April 2013 whole blood samples were collected by convenience from 151 cats (86 domiciled and 65 stray cats). The feline blood samples were subjected to a novel quantitative 5' nuclease real-time PCR (qPCR) for Bartonella species targeting the nictonamide adenine dinucleotide dehydrogenase gamma subunit (nuoG) and conventional PCR assays targeting intergenic transcribed spacer, ribC, gltA, pap31 and rpoB, followed by sequencing and basic local alignment search tool analysis. RESULTS: The qPCR assay detected as few as 10 copies of plasmid per reaction. Forty-six (54.4% domiciled and 45.6% stray cats) of 151 sampled cats showed positive results in nuoG qPCR for Bartonella species. The absolute quantification of nuoG Bartonella DNA in sampled cats ranged from 1.1 * 10(4) to 1.3 * 10(4). Eighteen (39.1%) of 46 positive samples in the qPCR were also positive in conventional PCR assays. The sequencing confirmed that Bartonella henselae and Bartonella clarridgeiae circulate in cats in midwestern Brazil. CONCLUSIONS AND RELEVANCE: The present work provides details of a novel qPCR assay to diagnose infections caused by Bartonella species. PMID- 26138813 TI - Commentary: drugs from bugs. PMID- 26138814 TI - The aromatic stacking interactions between proteins and their macromolecular ligands. AB - Aromatic stacking interactions arise from the attractive force between the pi electron clouds in the neighboring aromatic groups. The aromatic stacking is common between proteins and small molecules. The stacking interactions at the interfaces of proteins and other macromolecules are relatively rare. However it contributes to a significant portion of the stabilizing forces. In the proteinprotein complexes, aromatic interactions are involved in the protein oligomerization, such as dimer, trimer and tetramer formation. Also, aromatic residues can bind to nanoparticles through stacking interactions which offer them stronger affinity than other residues. These interactions play crucial roles in proteinnanoparticle conjugation. In the protein-nucleotide complexes, the specific recognitions are realized through stacking interactions between aromatic residues and the bases in the nucleotides. Many nucleoproteins use aromatic stacking to recognize binding site on DNA or RNA. Stacking interactions are involved in the process of mismatch repair, strand separation, deadenylation, degradation and RNA cap binding. They are proved to be important for the stability of complexes. The aromatic stacking is also the underlying reasons of many fatal diseases such as Alzheimer, cancer and cardiovascular diseases. The chemicals that can block the stacking interactions could have potential pharmaceutical values. In this review, we summarize recent finding regarding the functions of aromatic stacking interactions in the protein-macromolecule complexes. Our aim is to understand the mechanisms underlying the stacking mediated complex formation and facilitate the development of drugs and other bio products. PMID- 26138815 TI - Erratum: the polymorphic nature of membrane-active peptides from biophysical and structural investigations. PMID- 26138816 TI - Recovery from musculoskeletal injury: the role of social support following a transport accident. AB - BACKGROUND: Social support can be an important coping resource for persons recovering from injury. In this study, we examined the effects of family structure and sources of social support on physical health, persistent pain and return to work (RTW) outcomes following musculoskeletal injury (MSI) sustained in a transport accident. METHODS: Secondary analysis of Transport Accident Commission (TAC) cross-sectional surveys held in 2010 and 2011 was conducted. In total 1649 persons with MSI were identified and included. Family structure was determined by marital status and number of children. Sources of social support were measured as perceived help from family, friends, neighbours and employers. Physical health was measured with the Physical Component Summary (PCS) score of the Short-Form-12 Health Survey Version 2. Persistent pain was defined as self reported persistent pain experienced in the last 3 months, and RTW was defined as being back at work for >=3 months at time of interview. Multiple linear and logistic regressions were used for the analyses. RESULTS: Family and friends' support was associated with better physical health among persons with >1 day hospital stay. Being married or in a de facto relationship was associated with greater PCS score among non-hospitalised persons. Being widowed/separated/divorced was associated with more self-reported persistent pain (odds ratio 1.62 [95 % confidence intervals 1.11-2.37]). Support from family (0.40 [0.24-0.68]), friends (0.29 [0.17-0.47]) and neighbours (0.59 [0.41-0.84]) was associated with less persistent pain. Among women, support from family (0.09 [0.01-0.78]) was negatively associated with RTW, whereas support from friends (3.03 [1.15-8.02]) was positively associated with RTW. These associations were not observed among men. For both men (5.62 [2.77-11.38]) and women (7.22 [2.58 20.20]), support from employers was positively associated with RTW. CONCLUSION: Family structure and sources of social support had a positive impact on physical health, persistent pain and RTW following MSI. This study highlights the importance of identifying people who have limited access to a social support network. Those with limited access to social support after a transport accident could potentially benefit from the provision of formal sources of practical and psychological support. PMID- 26138817 TI - High-throughput phenotyping and genetic linkage of cortical bone microstructure in the mouse. AB - BACKGROUND: Understanding cellular structure and organization, which plays an important role in biological systems ranging from mechanosensation to neural organization, is a complicated multifactorial problem depending on genetics, environmental factors, and stochastic processes. Isolating these factors necessitates the measurement and sensitive quantification of many samples in a reliable, high-throughput, unbiased manner. In this manuscript we present a pipelined approach using a fully automated framework based on Synchrotron-based X ray Tomographic Microscopy (SRXTM) for performing a full 3D characterization of millions of substructures. RESULTS: We demonstrate the framework on a genetic study on the femur bones of in-bred mice. We measured 1300 femurs from a F2 cross experiment in mice without the growth hormone (which can confound many of the smaller structural differences between strains) and characterized more than 50 million osteocyte lacunae (cell-sized hollows in the bone). The results were then correlated with genetic markers in a process called quantitative trait localization (QTL). Our findings provide a mapping between regions of the genome (all 19 autosomes) and observable phenotypes which could explain between 8-40 % of the variance using between 2-10 loci for each trait. This map shows 4 areas of overlap with previous studies looking at bone strength and 3 areas not previously associated with bone. CONCLUSIONS: The mapping of microstructural phenotypes provides a starting point for both structure-function and genetic studies on murine bone structure and the specific loci can be investigated in more detail to identify single gene candidates which can then be translated to human investigations. The flexible infrastructure offers a full spectrum of shape, distribution, and connectivity metrics for cellular networks and can be adapted to a wide variety of materials ranging from plant roots to lung tissue in studies requiring high sample counts and sensitive metrics such as the drug-gene interactions and high-throughput screening. PMID- 26138818 TI - Influence of age-related learning and memory capacity of mice: different effects of a high and low caloric diet. AB - BACKGROUND: Recent studies indicate that consumption of the different calorie diet may be an important way to accelerate or slow the neurodegenerative disorder related to age. Long-term consumption of a high-calorie diet affects the brain and increase the risk of neurodegenerative disorders. And consumption of a low calorie diet (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms have not yet been clearly defined. METHOD: Thirty 6-week-old C57/BL6 mice were randomly assigned to a NC group (fed standard diet, n = 10), a CR group (fed a low-calorie diet, n = 10) or a HC group (fed a high-calorie diet, n = 10) for 10 months. Body weight was measured monthly. Learning and memory capacity were determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of GFAP was determined by immunofluorescence and western blot. The expression of mTOR, S6K and LC3B in the hippocampus was determined by immunofluorescence. RESULTS: After feeding for 10 months, compared with mice in the NC group, mean body weight was significantly higher in the HC group and significantly lower in the CR group. The result of Morris water maze showed that compared with mice in the NC group, the learning and memory capacity was significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining of the hippocampus showed cells damaged obviously in the HC group. In the hippocampus, the expression of GFAP, mTOR and S6K was increased in the HC group, and decreased in the CR group. The expression of LC3B was decreased in the HC group, and increased in the CR group. CONCLUSIONS: Long-term consumption of a high-calorie diet could inhibit autophagy function, and facilitate neuronal loss in the hippocampus, which in turn aggravate age-related cognition impairment. And consumption of a low-calorie diet (caloric restriction, CR) could enhance the degree of autophagy, protect neurons effectively against aging and damage, and keep learning and memory capacity better. PMID- 26138819 TI - Age and gender differences in spatial perspective taking. AB - BACKGROUND AND AIMS: It is often necessary in daily experience to change one's point of view to adopt mentally the spatial perspective of other persons, learn the position of different objects in a new environment or even describe an environment to other persons. Hence, the ability to link spatial information from different perspectives seems to be necessary to orient ourselves in the space. Several studies have found gender-related differences in spatial reasoning in younger adults, but little is known about such effects in middle-aged and older adults. METHODS: This research was designed to study how spatial perspective taking is affected by gender and age along the lifespan. The Perspective Taking/Spatial Orientation Test (PPT; Kozhevnikov and Hegarty [1]) was administered to groups of younger, middle-aged, and older adults, with females and males represented in each age group. RESULTS: The performance in the PPT decreased across age groups. All age groups had more errors in items that involved perspective changes of greater than 90o. Males performed better than females on most of the variables; however, no significant differences appeared in the interaction gender * age. CONCLUSION: The present findings showed the relevance of the degree perspective change in visuo-spatial abilities, especially in the older group. In relation with the gender, males outperformed females; however, the interaction gender * age did not show significant differences. PMID- 26138820 TI - Preregistration: when shall we start the real discussion? PMID- 26138821 TI - Credibility of observational studies: why public health researchers should care? PMID- 26138822 TI - Diversity and relationships of Crocus sativus and its relatives analysed by inter retroelement amplified polymorphism (IRAP). AB - BACKGROUND AND AIMS: Saffron (Crocus sativus) is a sterile triploid (2n = 3x = 24) cultivated species, of unknown origin from other diploid and polyploid species in the genus Crocus (Iridaceae). Species in the genus have high morphological diversity, with no clear phylogenetic patterns below the level of section Crocus series Crocus. Using DNA markers, this study aimed to examine the diversity and relationships within and between species of Crocus series Crocus. METHODS: Eleven inter-retroelement amplified polymorphism (IRAP) primers were used in 63 different combinations with 35 single-plant accessions of C. sativus and related Crocus species in order to determine genetic variability and to conduct phylogenetic analysis. KEY RESULTS: A total of 4521 distinct polymorphic bands from 100 bp to approx. 4 kb were amplified; no fragment specific to all accessions of a single species was amplified. The polymorphic information content (PIC) values varied from approx. 0.37 to approx. 0.05 (mean 0.17 +/- 0.1) and the major allele frequency had a mean of 0.87. High levels of polymorphism were identified between accessions of the six species of Crocus series Crocus related to C. sativus, with further variation between the species. In contrast, no polymorphisms were seen among 17 C. sativus accessions obtained in the region from Kashmir through Iran to Spain. CONCLUSIONS: In contrast to the intraspecific variability seen in other Crocus species, C. sativus has minimal genetic variation, and it is concluded that the triploid hybrid species has most probably arisen only once. The data show that saffron is an allotriploid species, with the IRAP analysis indicating that the most likely ancestors are C. cartwrightianus and C. pallasii subsp. pallasii (or close relatives). The results may facilitate resynthesizing saffron with improved characteristics, and show the need for conservation and collection of wild Crocus. PMID- 26138823 TI - The impact of an increase in excise tax on the retail price of tobacco in New Zealand. AB - BACKGROUND: In 2010, the New Zealand (NZ) government introduced an annual 10% tobacco excise tax increase. We examined retailers' adherence to recommended retail prices (RRP), and whether the RRP included the full tax increase. METHODS: We collected price data on three British American Tobacco (BAT) factory-made cigarette brands, (premium, mainstream, and budget), and one roll-your-own tobacco brand before and after the 2014 tax increase from a sample of tobacco retailers. We examined price increases in each tobacco brand and compared these with the RRP. The extent to which the excise tax increases had been included in the RRP since 2010 was estimated using data sourced from the Ministry of Health and NZ Customs. FINDINGS: The median increase in price from before to after the tax change was only 3% for the budget brand (461 retailers). This contrasted with the median of 8% for the premium brand (448 retailers), and 11% for both mainstream and roll-your-own brands (471 and 464 retailers, respectively). While many retail outlets made changes according to the RRP set by BAT, several did not comply. Our analyses suggest BAT may be undershifting excise tax on the budget brand, and overshifting tax on brands in other price partitions. CONCLUSIONS: Tobacco companies do not appear to be increasing the RRPs of budget brands in line with tobacco excise tax increases. The increasing price differential between budget brands, and mainstream and premium brands may undermine cessation and impede realisation of New Zealand's Smokefree 2025 goal. PMID- 26138824 TI - Nasal Chondromesenchymal Hamartoma (NCMH): a systematic review of the literature with a new case report. AB - BACKGROUND: Nasal chondromesenchymal hamartoma (NCMH) is a very rare, benign tumour of the sinonasal tract usually presenting in infants. We present a systematic review of NCMH cases alongside a case report of an adult with asymptomatic NCMH. METHODS: A systematic review was conducted in accordance with PRISMA guidelines. A PubMed, EMBASE and manual search through references of relevant publications was used to identify all published case-reports of NCMH. Data was collected from each case-report on: patient demographics, laterality, size and location of NCMH, presentation, co-morbidities, investigations, treatment and follow-up. RESULTS: The systematic review identified 48 patients (including ours): 33 male, 15 female. Mean age was 9.6 years (range: 1 day-69 years) with the majority aged 1 year or younger at presentation (n = 18). Presentations included: nasal congestion (n = 17), nasal mass (n = 15) and eye signs (n = 12). NCMH also involved the paranasal sinuses (n = 26), orbit (n = 16) and skull-base (n = 14). All patients underwent operative resection of NCMH. A small 2014 case-series found DICER1 mutations in 6 NCMH patients, establishing a link to the DICER1 tumour spectrum. CONCLUSIONS: NCMH is a rare cause of nasal masses in young children and adults. In light of the newly established link between NCMH and DICER1 mutations surgeons should be vigilant for associated DICER1 tumours, as NCMH may be the 'herald tumour' of this disease spectrum. PMID- 26138825 TI - Analysis of social networks supporting the self-management of type 2 diabetes for people with mental illness. AB - BACKGROUND: People with mental illness have been identified as being more likely to experience type 2 diabetes and the complications arising from this, necessitating more complex chronic illness self-management. Social support has been identified as a significant factor in the successful adoption of lifestyle change for people with type 2 diabetes, however people with mental illness often have impoverished social networks leading to greater reliance upon professional care givers. This study maps the support provided by formal (paid and professional carers) and informal networks to people with mental illness and type 2 diabetes, comparing the experiences of people with a spouse with those without one. METHODS: Interviews were conducted with 29 clients of a community nursing service with mental health problems who receive professional support to self manage type 2 diabetes. Participants were asked to complete an egocentric social network map which involved mapping the people and services who support them to manage their health. Demographic data was collected as was data about co morbidities and service use within the last 6 months. Network maps were supplemented by a series of open-ended questions about self-management practices, who supports these practices and what support they provide. RESULTS: Participants identified small social networks with few friendship ties. These networks had diminished due to illness. For people with a spouse, this person provided significant support for chronic illness self-management performing a range of daily care and illness management tasks. People without a spouse were more reliant on professional and paid care givers for daily care and illness management. People without a spouse also demonstrated greater reliance upon weak social ties for emotional support and social connection and often developed friendships with formal caregivers. CONCLUSIONS: Spousal support reduces the need for professional services. In the absence of a spouse, participants were more reliant upon paid and professional carers and weaker social ties for chronic illness support and social connection leading to greater vulnerability of loss of support. PMID- 26138826 TI - RNA Editing of the GP Gene of Ebola Virus is an Important Pathogenicity Factor. AB - Synthesis of the surface glycoprotein GP of Ebola virus (EBOV) is dependent on transcriptional RNA editing, whereas direct expression of the GP gene results in synthesis of nonstructural secreted glycoprotein sGP. In this study, we investigate the role of RNA editing in the pathogenicity of EBOV using a guinea pig model and recombinant guinea pig-adapted EBOV containing mutations at the editing site, allowing expression of surface GP without the need for RNA editing, and also preventing synthesis of sGP. We demonstrate that the elimination of the editing site leads to EBOV attenuation in vivo, explained by lower virus spread caused by the higher virus cytotoxicity and, most likely, by an increased ability of the host defense systems to recognize and eliminate virus-infected cells. We also demonstrate that expression of sGP does not affect pathogenicity of EBOV in guinea pigs. In conclusion, data obtained indicate that downregulation of the level of surface GP expression through a mechanism of GP gene RNA editing plays an important role in the high pathogenicity of EBOV. PMID- 26138827 TI - Contralateral neck failure in lateralized oral squamous cell carcinoma. AB - BACKGROUND: Elective treatment of the contralateral clinically node-negative (cN0) neck is not routinely recommended for lateralized oral cavity squamous cell carcinoma (SCC). We sought to determine the failure rate in the untreated contralateral neck in patients with lateralized oral SCC undergoing treatment of the primary and ipsilateral neck and to identify any features placing patients at sufficient risk of contralateral regional failure to justify elective treatment. METHODS: We identified 688 patients with oral SCC undergoing curative surgery +/- adjuvant therapy between 1985 and 2012 from a prospectively collected database. Patients with midline primaries and those undergoing bilateral neck treatment were excluded. The primary endpoint was isolated contralateral neck failure. RESULTS: Of 481 patients, 14 (2.9%) developed isolated contralateral neck recurrence, with median time to recurrence of 8 months. Patients with poorly differentiated tumours or pathologically proven ipsilateral nodal metastases were at significantly higher risk of contralateral failure (hazard ratio (HR) 3.6, 95% confidence interval (CI) 1.1-11.9, P = 0.037 and HR 4.6, 95% CI 1.5-13.8, P = 0.006 respectively). Presence of both of these factors conferred a 10% risk of contralateral failure. CONCLUSION: Patients with lateralized oral SCC undergoing treatment of the primary tumour and ipsilateral neck have a low rate of isolated contralateral neck failure. Although poorly differentiated primaries and ipsilateral nodal metastases were predictors of contralateral recurrence, the risk remains relatively modest in this subset of patients suggesting close observation may be more appropriate than elective treatment. Our results support current recommendations for observation of the cN0 contralateral neck in lateralized oral SCC. PMID- 26138829 TI - Industry-Funded Continuing Medical Education: The Potential for Bias. PMID- 26138828 TI - Infused autograft lymphocyte-to-monocyte ratio and survival in T-cell lymphoma post-autologous peripheral blood hematopoietic stem cell transplantation. AB - BACKGROUND: The infused autograft lymphocyte-to-monocyte ratio (A-LMR) is a prognostic factor for survival in B-cell lymphomas post-autologous peripheral hematopoietic stem cell transplantation (APHSCT). Thus, we set out to investigate if the A-LMR is also a prognostic factor for survival post-APHSCT in T-cell lymphomas. METHODS: From 1998 to 2014, 109 T-cell lymphoma patients that underwent APHSCT were studied. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to identify the optimal cut-off value of A-LMR for survival analysis and k-fold cross-validation model to validate the A-LMR cut off value. Univariate and multivariate Cox proportional hazard models were used to assess the prognostic discriminator power of A-LMR. RESULTS: ROC and AUC identified an A-LMR >= 1 as the best cut-off value and was validated by k-fold cross-validation. Multivariate analysis showed A-LMR to be an independent prognostic factor for overall survival (OS) and progression-free survival (PFS). Patients with an A-LMR >= 1.0 experienced a superior OS and PFS versus patients with an A-LMR < 1.0 [median OS was not reached vs 17.9 months, 5-year OS rates of 87% (95% confidence interval (CI), 75-94%) vs 26% (95% CI, 13-42%), p < 0.0001; median PFS was not reached vs 11.9 months, 5-year PFS rates of 72% (95% CI, 58 83%) vs 16% (95% CI, 6-32%), p < 0.0001]. CONCLUSIONS: A-LMR is also a prognostic factor for clinical outcomes in patients with T-cell lymphomas undergoing APHSCT. PMID- 26138830 TI - Enhancement of electroluminescence from embedded Si quantum dots/SiO2multilayers film by localized-surface-plasmon and surface roughening. AB - In this paper, we prepared a novel structure to enhance the electroluminescence intensity from Si quantum dots/SiO2multilayers. An amorphous Si/SiO2 multilayer film was fabricated by plasma-enhanced chemical vapor deposition on a Pt nanoparticle (NP)-coated Si nanopillar array substrate. By thermal annealing, an embedded Si quantum dot (QDs)/SiO2 multilayer film was obtained. The result shows that electroluminescence intensity was significantly enhanced. And, the turn-on voltage of the luminescent device was reduced to 3 V. The enhancement of the light emission is due to the resonance coupling between the localized-surface plasmon (LSP) of Pt NPs and the band-gap emission of Si QDs/SiO2 multilayers. The other factors were the improved absorption of excitation light and the increase of light extraction ratio by surface roughening structures. These excellent characteristics are promising for silicon-based light-emitting applications. PMID- 26138831 TI - Comparison between Plain Old Balloon Angioplasty and Drug-Eluting Stent Implantation for the Treatment of Stent Fracture. AB - OBJECTIVES: The aim of this study was to evaluate clinical outcomes after percutaneous coronary intervention (PCI) for stent fracture (SF). BACKGROUND: SF has been reported as a predictor of in-stent restenosis (ISR) and stent thrombosis (ST). METHODS: Between January 2009 and December 2012, consecutive SF cases treated with either drug-eluting stent (DES) or plain old balloon angioplasty (POBA) were retrospectively enrolled in this study. The study endpoints were all-cause death, cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), target lesion revascularization (TLR), ST, re stent fracture (re-SF), and major adverse cardiac events (MACE) defined as the composite of cardiac death, MI, and TLR. RESULTS: Of 135 SF cases, 67 (49.6%) cases were treated with DES, whereas 68 (50.4%) cases with POBA. Median follow-up period was 1,401 (IQR: 967-1,771) days. The estimated MACE rate at 3 years was significantly lower in the DES group as compared with the POBA group largely driven by less TLR (25.7 vs. 55.8%, P < 0.001). Moreover, 1-year landmark analysis after PCI for SF revealed that MACE continued to occur even after 1 year irrespective of the treatment option (P = 0.47). On multivariable Cox regression analysis, POBA and large post-procedure angle (Delta) defined as the degree difference between the end systolic and diastolic angle were identified as independent predictors for TLR. CONCLUSIONS: DES implantation for SF is associated with better clinical outcomes as compared to POBA alone, due to a lower need for TLR. Large post-procedural angle (Delta) appears to be an independent predictor of TLR. PMID- 26138832 TI - Voyages of Discovery. AB - The metabolism of calcium and bone is controlled by five principal hormones: parathyroid hormone, 1,25-dihydroxyvitamin D, calcitonin, parathyroid hormone related peptide and fibroblast growth factor 23, some of which have been known for several decades and some of which have only more recently been identified. The stories of the discovery of these hormones have constituted a series of complex journeys that have been undertaken over the past century or so, none of which has yet been completed. The complexities of bone and calcium metabolism have been and remain, to many people, somewhat mysterious and a daunting task to understand. This book is designed to try to unravel those mysteries and present them in an interesting and comprehensible manner. PMID- 26138833 TI - Physiology of Calcium, Phosphate, Magnesium and Vitamin D. AB - The physiology of calcium and the other minerals involved in its metabolism is complex and intimately linked to the physiology of bone. Five principal humoral factors are involved in maintaining plasma concentrations of calcium, magnesium and phosphate and in coordinating the balance between their content in bone. The transmembrane transport of these elements is dependent on a series of complex mechanisms that are partly controlled by these hormones. The plasma concentration of calcium is initially sensed by a calcium-sensing receptor, which then sets up a cascade of events that initially determines parathyroid hormone secretion and eventually results in a specific action within the target organs, mainly bone and kidney. This chapter describes the physiology of these humoral factors and relates them to the pathological processes that give rise to disorders of calcium, phosphate and magnesium metabolism as well as of bone metabolism. This chapter also details the stages in the calcium cascade, describes the effects of calcium on the various target organs, gives details of the processes by which phosphate and magnesium are controlled and summarises the metabolism of vitamin D. The pathology of disorders of bone and calcium metabolism is described in detail in the relevant chapters. PMID- 26138834 TI - Physiology of Bone. AB - Bone serves three main physiological functions: its mechanical nature provides support for locomotion and offers protection to vulnerable internal organs, it forms a reservoir for the storage of calcium and phosphate in the body, and it provides an environment for bone marrow production and haematopoietic cell development. The traditional view of bone as a passive tissue that responds to hormonal and dietary influences has changed over the past half century to one of bone as a dynamic adaptive tissue that responds to mechanical demands. This chapter gathers together some recent advances in bone physiology and molecular cell biology and discusses the potential application of the functional adaptation of bone to loading to enhance bone strength during childhood and adolescence. PMID- 26138835 TI - Radiology of Osteogenesis Imperfecta, Rickets and Other Bony Fragility States. AB - This section gives an overview of radiological findings in bony fragility states, with a special focus on osteogenesis imperfecta (OI) and rickets. Conventional radiological assessment of bone density is inaccurate and imprecise and only reliably detects severe osteopaenia. However, other aspects of bone structure and morphology can be assessed, and it is possible to distinguish between osteopaenic and osteomalacic states. OI is a heterogeneous group of disorders of type 1 collagen formation and processing that are characterised by varying degrees of bony fragility, with presentations varying from perinatal lethality to asymptomatic. Radiological diagnosis of severe forms is usually straightforward, but that of milder disease may be challenging because specific features are often absent. However, a multidisciplinary approach is usually successful. Features of OI, including Wormian bones, skull base deformities, vertebral involvement and long bone fractures and deformities, are reviewed in this section. Rickets is best defined as a disorder of the growth plate characterised by the impaired apoptosis of hypertrophied chondrocytes. Vitamin D deficiency is a common cause of rickets. The patho-anatomical basis of radiological findings in rickets is reviewed and illustrated. Rickets is frequently accompanied by hyperparathyroidism and osteomalacia. Rickets used to be classified as calciopaenic or phosphopaenic but is now referred to as parathyroid hormone or fibroblast growth factor 23 mediated, respectively [1]. The radiological features of the two forms are reviewed. PMID- 26138836 TI - Bone Densitometry: Current Status and Future Perspective. AB - In this chapter, we discuss the concept of what determines bone strength and fracture risk and how this can be quantified using current technologies. We describe bone densitometry measurement techniques that are currently available and consider the strengths and limitations of each technique, with particular emphasis on paediatric scanning. Magnetic resonance imaging is reviewed, as it is one of the newer technologies applied to assessment of the growing skeleton. The role of dual-energy X-ray absorptiometry and quantitative computed tomography in the clinical assessment of bone health in children is considered, and their current diagnostic application is reviewed. PMID- 26138837 TI - A Practical Approach to Hypocalcaemia in Children. AB - Hypocalcaemia is one of the commonest disorders of mineral metabolism seen in children and may be a consequence of several different aetiologies. These include a lack of secretion or function of parathyroid hormone, disorders of vitamin D metabolism and abnormal function of the calcium-sensing receptor. A practical approach to the investigation, diagnosis and subsequent management of hypocalcaemic disorders is presented. PMID- 26138838 TI - Approach to the Child with Hypercalcaemia. AB - Hypercalcaemia is rare in children. In adulthood, the causes are most frequently malignancy and primary hyperparathyroidism. In children, however, the aetiologies are diverse and age specific, and many have an underlying genetic basis. Hypercalcaemia is a serious condition that frequently leads to end-organ damage. In order to provide the most appropriate treatment, a key part of the management pathway is to establish the correct diagnosis promptly. When considering a practical approach to hypercalcaemia in children, it is helpful to consider the causes of hypercalcaemia according to the accompanying levels of parathyroid hormone (PTH), indicating whether the causes are PTH dependent or PTH independent. This chapter reviews the recent advances in this area and presents a practical approach to the investigation and subsequent management of this condition. PMID- 26138839 TI - A Practical Approach to Vitamin D Deficiency and Rickets. AB - Rickets is a condition in which there is failure of the normal mineralisation (osteomalacia) of growing bone. Whilst osteomalacia may be present in adults, rickets cannot occur. It is generally caused by a lack of mineral supply, which can either occur as a result of the deficiency of calcium (calciopaenic rickets, now known as parathyroid hormone-dependent rickets) or of phosphate (phosphopaenic rickets, now called FGF23-dependent rickets). Renal disorders may also interfere with the process of mineralisation and cause rickets. Only parathyroid hormone-dependent rickets and distal renal tubular disorders will be discussed in this chapter. The most common cause of rickets is still vitamin D deficiency, which is also responsible for other problems. Disorders of vitamin D metabolism or responsiveness may also cause similar issues. Distal renal tubular acidosis may also be caused by a variety of metabolic errors similar to those of osteoclasts. One form of distal renal tubular acidosis also causes a type of osteopetrosis. This chapter describes these conditions in detail and sets out a logical approach for treatment. PMID- 26138840 TI - A Practical Clinical Approach to Paediatric Phosphate Disorders. AB - Phosphate metabolism is critical to multiple systems and cellular functions. Disruption of any point in the pathways of phosphate metabolism may cause serum phosphate abnormalities and resultant acute or chronic clinical conditions. The study of phosphate disorders has revealed a wealth of information regarding normal phosphate physiology. Careful evaluation of affected patients based on pathophysiologic assessments will usually identify the aetiology of hypophosphataemia or hyperphosphataemia, which is important to guide appropriate therapy. Because of the relative importance of chronic hypophosphataemia and hyperphosphataemia to bone disease, much of this chapter will focus on chronic disorders, especially those mediated by excess or deficient fibroblast growth factor 23 functioning. PMID- 26138841 TI - Primary Osteoporosis. AB - Primary osteoporosis in childhood encompasses a range of bone fragility conditions that typically have a genetic origin. Understanding of the pathophysiology and genetics of primary osteoporosis has increased dramatically over the past 10 years. The clinical manifestations and consequences of the disease range from mild to severe, with the degree of growth retardation and bony deformity reflecting the severity and the underlying pathology. In children, primary osteoporosis is most commonly caused by one of the forms of osteogenesis imperfecta, which comprises a group of disorders characterised by abnormalities in type I collagen synthesis or processing. Diagnosis of any primary osteoporotic condition depends on the clinical history and examination but may be supported by other investigations, including various imaging techniques, histology and genetic analyses. Good management requires a multidisciplinary approach involving paediatricians, surgeons and allied health professionals, amongst others. Bisphosphonate therapy has revolutionised the approach to management and has positively modified outcomes for many children and their families. Physiotherapy and occupational therapy are the keys to optimising independence in mobility and daily living. Surgery is required in many severe cases to straighten limbs or stabilise the spine. Bisphosphonates remain the mainstay of medical treatment, but there are a number of alternative therapeutic agents under investigation that may further improve management of primary osteoporosis in children over the coming years. PMID- 26138842 TI - Osteoporosis in Children with Chronic Disease. AB - Serious illness in children and its therapy can cause osteoporosis, manifesting as vertebral and nonvertebral fractures, pain, skeletal deformity and temporary or even permanent loss of ambulation. In contrast to adults, skeletal growth in children offers tremendous potential to recover bone mineral density and to reshape fractured vertebral bodies, even without bone-targeted therapy, provided that bone health threats are transient and residual growth is sufficient. Here, we outline the principles of bone strength development and the risk factors for osteoporosis due to various paediatric systemic illnesses. We also explain why the approach to the diagnosis and monitoring of childhood osteoporosis has moved away from a bone density-centric focus to a more functional assessment. Finally, we discuss the best candidates for and current approaches to the treatment of osteoporosis in children. PMID- 26138843 TI - Genetics of Osteoporosis in Children. AB - In the pathogenesis of paediatric osteoporosis, genetic causes may play an important role. The most prevalent monogenic cause of paediatric osteoporosis is osteogenesis imperfecta, a disorder characterised primarily by liability to fractures. With regard to diagnosis or exclusion of a monogenic cause of paediatric osteoporosis, clinical practice has changed rapidly in recent years. This is largely due to the discovery of many new genetic causes in patients with a clear clinical diagnosis of osteogenesis imperfecta but also due to the identification of genetic causes in patients with isolated or non-syndromal osteoporosis with fractures. In this chapter, known monogenic causes of syndromal and non-syndromal osteoporosis in children will be described. Furthermore, we will discuss when to refer for clinical genetic evaluation as well as the current and future merits of genetic evaluation of children with osteoporosis. PMID- 26138844 TI - A Practical Approach to Children with Recurrent Fractures. AB - As many as 50% of children will sustain a fracture before 18 years of age, and up to 20% will have two or more fractures. A small proportion of children who experience multiple fractures have osteoporosis, either from a genetic bone disorder (primary osteoporosis) or secondary to another underlying medical condition (secondary osteoporosis). Fracture history, together with bone mineral density assessment and vertebral radiographs, help clinicians to identify children with osteoporosis. Its aetiology can usually be determined through the combination of a detailed medical history and physical examination, laboratory investigations to assess mineral homeostasis, evaluation of secondary causes of osteoporosis and genetic studies to identify the underlying cause of the disorder. Transiliac bone biopsy with histology and histomorphometry should not be overlooked as valuable tools for the investigation of a child with osteoporosis of uncertain aetiology. Optimal management of osteoporosis requires a multidisciplinary team to address physical activity, nutrition, pubertal progression, the management of any underlying medical condition, pharmacotherapy (bisphosphonates) and orthopaedic surgery. This chapter outlines an approach to the evaluation and treatment of children with recurrent fractures and describes three common scenarios involving infants, children with chronic illness and children without chronic illness. PMID- 26138845 TI - Miscellaneous Bone Disorders. AB - This chapter deals with a few of the important childhood bone disorders associated with high bone mass as well as conditions associated with fragility fractures and limb deformities that have not been addressed in previous chapters. A couple of skeletal dysplasias that can sometimes be confused with rickets are also dealt with in this chapter. PMID- 26138846 TI - Skeletal Aspects of Non-Accidental Injury. AB - Inflicted non-accidental skeletal injuries form a small but important part of the spectrum of child abuse, with the majority of skeletal injuries occurring in children under 2 years of age. Radiology plays a vital role in the detection and evaluation of these skeletal injuries. A thorough detailed radiological evaluation should be undertaken to investigate a child appropriately for a suspected inflicted non-accidental injury to accurately detect and possibly date any injuries and also to exclude normal variants of growth that may mimic fractures. In some cases, the survey may diagnose an underlying metabolic or genetic disorder of the bone that may predispose the child to fracturing. While radiology plays an important role in the dating of injuries, the dating of fractures from radiological appearances is difficult and imprecise. Any fracture may be the result of an inflicted injury or accidental event. Therefore, it is important that all fractures identified are correlated with any relevant clinical history. Certain injuries, such as rib and metaphyseal fractures, require a more specific method of causation and therefore carry a higher degree of suspicion of being the result of an inflicted injury compared with other fracture types, which are relatively non-specific in their mechanisms of causation, such as skull and clavicular fractures. In all cases, correlation with clinical history is mandatory. PMID- 26138847 TI - Skeletal Dysplasias: An Overview. AB - Constitutional disorders of bone, commonly termed skeletal dysplasias (SDs), are inherited disorders of cartilage and/or bone that affect their growth, morphometry and integrity. Associated skeletal abnormalities are usually but not invariably symmetrical. They may be classified as osteochondrodysplasias, which are conditions associated with abnormalities of the growth (dysplasias) or texture (osteodystrophy) of bone and/or cartilage, or dysostoses, which are conditions secondary to abnormal blastogenesis (occurring at or around the 6th week of in utero life). Skeletal involvement may also occur in other multisystem hereditary and acquired syndromes. The 2010 Nosology and Classification of Genetic Skeletal Disorders listed 456 conditions, of which approximately 50 are perinatally lethal, and 316 are associated with one or more of 226 genes. When an SD is suspected, a standard series of radiographs, collectively known as a skeletal survey, should be performed. The diagnosis of individual conditions is highly dependent on radiographic pattern recognition, which is achieved through a systematic review of the images and enhanced by discussion with colleagues and through the use of available tools, such as atlases and digital databases. This article summarises a systematic approach to the diagnosis of SDs, demonstrated using examples of some of the more common lethal and non-lethal conditions. PMID- 26138848 TI - Drugs Used in Paediatric Bone and Calcium Disorders. AB - Calcium and bone disorders in children and adolescents are treated with a wide variety of drugs. Several of these drugs have been used for many years on the basis of accepted practice, without being subjected to rigorous trials. Bisphosphonates are the mainstay treatment for children with osteoporosis, but newer, more potent compounds such as zoledronate and risedronate have begun to replace the older-generation bisphosphonates. Hypocalcaemia is managed with calcium and vitamin D and its metabolites. In difficult cases that are secondary to hypoparathyroidism, subcutaneous injections or infusions of parathyroid hormone have been used. Multiple daily phosphate supplements and calcitriol are the standard treatment for hypophosphataemic rickets, but trials of an anti fibroblast growth factor 23 antibody appear promising, and the results are eagerly awaited. Many new medications are undergoing clinical trials and are starting to emerge as viable treatment options for children. Some of these drugs target specific diseases, such as recombinant alkaline phosphatase for hypophosphatasia and a C-type natriuretic peptide analogue for achondroplasia. Other drugs, such as denosumab and odanacatib, have been used successfully in the adult population, and the appropriate use of these drugs in children is now being evaluated. PMID- 26138849 TI - Classification of Disorders of Bone and Calcium Metabolism. AB - Classification is a natural human trait that enables us to put what may otherwise be very complex subjects into some order. However, classification should be seen not as an end in itself but rather as a means to help us understand certain topics. In the case of medicine, classification helps to provide information about the causes underlying many of the conditions encountered and, in some cases, provides a rationale for developing new treatments. This chapter aims to provide a helpful (if complex) classification of diseases of bone and calcium and, where known, to describe the underlying genetic mechanisms. PMID- 26138850 TI - Case Histories. AB - Conditions related to abnormalities of calcium and bone metabolism are large in number and are characterised by hypocalcaemia, hypercalcaemia, primary and secondary osteoporosis, rickets resulting from both vitamin D and phosphate metabolism disorders, and a series of miscellaneous conditions. Included in this chapter is a series of cases drawn from our clinics and from colleagues who have presented these clinical problems at the recent Advanced Courses in Paediatric Bone and Calcium Metabolism run by the British Paediatric and Adolescent Bone group. This series of cases is not fully comprehensive but is designed to cover the major aspects of bone- and calcium-related disorders. PMID- 26138851 TI - Cytologic findings of NUT midline carcinoma in the hilum of the lung. AB - Nuclear protein in testis (NUT) midline carcinoma (NMC) is a clinically lethal malignancy affecting all age group often located in the midline structures such as mediastinum, larynx and nasopharynx. It is characterized by chromosomal translocation between chromosomes 15 and 19 with the formation of chimeric gene BRD-NUT. We present the cytologic findings of NMC including the immunohistochemical stains performed. The patient is a 34-year-old man who presented with 1 month history of dyspnea and interscapular pain followed by nonproductive cough a week before consultation. He was initially diagnosed with pneumonia. Due to progression of symptoms, a chest CT scan was performed revealing a large hilar mass and mediastinal adenopathy. A core biopsy with touch preparations of the hilar mass was performed which revealed cohesive malignant cells with ovoid to elongated nuclei, fine to coarse chromatin pattern, irregular nuclear contour, prominent nucleoli, and scant ill-defined cytoplasm arranged in sheets and focally pseudoglandular pattern. Although focal nuclear overlapping and crush artifact were identified, karyorrhectic debris and mitotic figures were rare. Squamous differentiation was absent. The core biopsy showed discohesive malignant cells with tumor necrosis. No nuclear molding, glandular or squamous differentiation was identified. The tumor was immunoreactive for p63 and NUT with high Ki-67 (>80%). The tumor was negative for keratin, lymphoid, myeloid, neuroendocrine markers and S-100. This case emphasizes that cytologic features of NMC can mimic poorly differentiated, undifferentiated and neuroendocrine carcinomas and the importance of immunohistochemical stains especially NUT monoclonal antibody in arriving at the diagnosis. PMID- 26138852 TI - The role of nanoscale defect features in enhancing the thermoelectric performance of p-type nanostructured SiGe alloys. AB - Despite SiGe being one of the most widely studied thermoelectric materials owing to its application in radioisotope thermoelectric generators (RTG), the thermoelectric figure-of merit (ZT) of p-type SiGe is still quite low, resulting in poor device efficiencies. In the present study, we report a substantial enhancement in ZT~ 1.2 at 900 degrees C for p-type nanostructured Si80Ge20 alloys by creating several types of defect features within the Si80Ge20 nanostructured matrix in a spectrum of nano to meso-scale dimensions during its nanostructuring, by employing mechanical alloying followed by spark plasma sintering. This enhancement in ZT, which is ~25% over the existing state-of-the art value for a p-type nanostructured Si80Ge20 alloy, is primarily due to its ultralow thermal conductivity of ~2.04 W m(-1) K(-1) at 900 degrees C, resulting from the scattering of low-to-high wavelength heat-carrying phonons by different types of defect features in a range of nano to meso-scale dimensions in the Si80Ge20 nanostructured matrix. These include point defects, dislocations, isolated amorphous regions, nano-scale grain boundaries and more importantly, the nano to meso-scale residual porosity distributed throughout the Si80Ge20 matrix. These nanoscale multi-dimensional defect features have been characterized by employing scanning and transmission electron microscopy and correlated with the electrical and thermal transport properties, based on which the enhancement of ZT has been discussed. PMID- 26138853 TI - Ozone monitoring using differential optical absorption spectroscopy (DOAS) and UV photometry instruments in Sohar, Oman. AB - Ground level ozone (O3) concentrations were measured across Sohar highway in Oman during a four-month period from September to December 2014 by using an open-path deferential optical absorption spectroscopy (DOAS) instrument. The monthly average concentrations of O3 varied from 19.6 to 29.4 ppb. The measurements of O3 are compared with the measurements of a non-open-path UV photometry analyzer (UVP). The percent difference (PD) concept and linear regression methods were used to compare the readings of the two instruments. The findings show high correlation coefficients between the measurements of the DOAS and UVP instruments. The DOAS measurements of O3 are found to be less than those measured by the UVP instrument; the correlation coefficients between absolute PD values and meteorological parameters and PM2.5 were very low indicating a minor effect; therefore, titrations of O3 by traffic emissions and difference in elevation could be the reason for the difference in the measurements of the two instruments. PMID- 26138854 TI - Biogeochemical characteristics of Rosa canina grown in hydrothermally contaminated soils of the Gumushane Province, Northeast Turkey. AB - Kirkpavli alteration area (Gumushane, Northeast Turkey) is contaminated by heavy metals such as Cd, Pb, As, Cu and Zn. The quantity of accumulation of heavy metal trace elements and macroelements in 32 leaves of Rosa canina of the Kirkpavli alteration area has been studied within the scope of geochemical studies. Element contents of samples were assessed using various parameters including descriptive statistics, factor analysis, correlation coefficients and bioaccumulation factor. Concentrations were detected in the acceptable range for Mo, Cu, Pb, Ni, As, Cd, Sb, P, Ti, Na, Se and Sn. Concentrations of Co, Mn, Ba and Hg were detected close to the acceptable values, whereas Zn, Fe, Sr, V, Ca, Cr, Mg, B, Al, K, W, Sc, Cs and Rb concentrations were detected above the acceptable values. Principal component analysis was used to identify the elements that have a close relationship with each other and/or similar origins. It has been concluded that Zn, Cu, As and Mo content of the plant were related to hydrothermal alteration process and they behaved together, whereas Mn and Fe were especially products of weathering conditions, also behaved together. In terms of macroelements, Ca, Mg and Na had similar behaviour, while P and K had the same correlation. PMID- 26138855 TI - Study protocol: cross-national comparative case study of recovery-focused mental health care planning and coordination (COCAPP). AB - BACKGROUND: The collaborative care planning study (COCAPP) is a cross-national comparative study of care planning and coordination in community mental healthcare settings. The context and delivery of mental health care is diverging between the countries of England and Wales whilst retaining points of common interest, hence providing a rich geographical comparison for research. Across England the key vehicle for the provision of recovery-focused, personalised, collaborative mental health care is the care programme approach (CPA). The CPA is a form of case management introduced in England in 1991, then revised in 2008. In Wales the CPA was introduced in 2003 but has now been superseded by The Mental Health (Care Co-ordination and Care and Treatment Planning) (CTP) Regulations (Mental Health Measure), a new statutory framework. In both countries, the CPA/CTP requires providers to: comprehensively assess health/social care needs and risks; develop a written care plan (which may incorporate risk assessments, crisis and contingency plans, advanced directives, relapse prevention plans, etc.) in collaboration with the service user and carer(s); allocate a care coordinator; and regularly review care. The overarching aim of this study is to identify and describe the factors that ensure CPA/CTP care planning and coordination is personalised, recovery-focused and conducted collaboratively. METHODS/DESIGN: COCAPP will employ a concurrent transformative mixed methods approach with embedded case studies. Phase 1 (Macro-level) will consider the national context through a meta-narrative mapping (MNM) review of national policies and the relevant research literature. Phase 2 (Meso-level and Micro level) will include in-depth micro-level case studies of everyday 'frontline' practice and experience with detailed qualitative data from interviews and reviews of individual care plans. This will be nested within larger meso-level survey datasets, senior-level interviews and policy reviews in order to provide potential explanations and understanding. DISCUSSION: COCAPP will help identify the key components that support and hinder the provision of personalised, recovery-focused care planning and provide an informed rationale for a future planned intervention and evaluation. PMID- 26138856 TI - Deferasirox Decreases Liver Iron Concentration in Iron-Overloaded Patients with Myelodysplastic Syndromes, Aplastic Anemia and Other Rare Anemias. AB - Iron overload in transfusion-dependent patients with rare anemias can be managed with chelation therapy. This study evaluated deferasirox efficacy and safety in patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemias. A 1-year, open-label, multicenter, single-arm, phase II trial was performed with deferasirox (10-40 mg/kg/day, based on transfusion frequency and therapeutic goals), including an optional 1-year extension. The primary end point was a change in liver iron concentration (LIC) after 1 year. Secondary end points included changes in efficacy and safety parameters (including ophthalmologic assessments) overall as well as in a Japanese subpopulation. Overall, 102 patients (42 with MDS, 29 with AA and 31 with other rare anemias) were enrolled; 57 continued into the extension. Mean absolute change in LIC was -10.9 mg Fe/g dry weight (d.w.) after 1 year (baseline: 24.5 mg Fe/g d.w.) and -13.5 mg Fe/g d.w. after 2 years. The most common drug-related adverse event was increased serum creatinine (23.5%), predominantly in MDS patients. Four patients had suspected drug-related ophthalmologic abnormalities. Outcomes in Japanese patients were generally consistent with the overall population. Results confirm deferasirox efficacy in patients with rare anemias, including a Japanese subpopulation. The safety profile was consistent with previous studies and ophthalmologic parameters generally agreed with baseline values (EUDRACT 2006 003337-32). PMID- 26138857 TI - MA104 Cell line presents characteristics suitable for enterovirus A71 isolation and proliferation. AB - Enterovirus A71 (EV-A71), one of the most important causative agents of hand, foot and mouth disease (HFMD) in children, can lead to severe clinical outcomes, even death. However, the infection spectrum of EV-A71 in different cell lines remains unknown. Therefore, in this study, the biological characteristics of EV A71 Subgroup C4 in different cell lines were investigated. To this end, the infectivity of EV-A71Jinan1002 isolated from children with severe HFMD was assessed in 18 different host cell lines. It was found that the MA104 cell line displayed biological characteristics suitable for EV-A71 Subgroup C4 strain isolation and proliferation; indeed, it was found that a broad spectrum of cell lines can be infected by EV-A71Jinan1002. Among the screened cells, four cell lines (HEK293, RD, MA104 and Marc145) produced high 50% tissue culture infective dose (TCID50 ) values calculated in viral proliferations (ranged from 10(7.6) to 10(7.8) ); the TCID50 being negatively associated with the time to appearance of CPE. Proliferation curves demonstrated that EV-A71Jinan1002 amplifies more efficiently in MA104, Hep-2 and RD cells. Remarkably, the virus isolation rate was much higher in MA104 cells than in RD cells. Thus this study, to our knowledge, is for the first to explore the infection spectrum of EV-A71 subgroup C4 in such a large number of different cell lines. Our data provide useful reference data for facilitating further study of EV-A71. PMID- 26138858 TI - Successful long-term ambulatory norepinephrine infusions in a patient with pure autonomic failure. AB - We present a case study of a patient with pure autonomic failure who was successfully treated with ambulatory norepinephrine (NE) infusions over a 9-year period of time before death occurred unexpectedly. Given this patient's response to the NE infusion treatment, we discuss the option of ambulatory NE infusions as a treatment for severe orthostatic hypotension that is refractory to common treatments. PMID- 26138859 TI - Bivalirudin in ST-segment-elevation myocardial infarction: for better or worse? AB - Bivalirudin and heparin are the major available parenteral anticoagulants for percutaneous coronary intervention (PCI) in ST-segment-elevation myocardial infarction. Even though hard clinical outcomes are comparable with both drugs, bivalirudin appears to be safer (less bleeding events) at the expense of lower short-term efficacy (more acute stent thrombosis events). The selection of anticoagulation during PCI in ST-segment-elevation myocardial infarction should be individualized, taking into account the patient's ischemic and bleeding risk. In patients with increased bleeding risk, bivalirudin might be preferable to heparin, whereas in complex PCI with increased risk for stent thrombosis, heparin is preferable. Further clinical studies are needed to elucidate the role of these drugs in PCI for ST-segment-elevation myocardial infarction in the era of radial approaches, new potent antiplatelet agents and the use of glycoprotein IIb/IIIa inhibitors. PMID- 26138860 TI - Differential Expression of Durum Wheat Gluten Proteome under Water Stress during Grain Filling. AB - Environmental stress during grain filling may affect wheat protein composition, thus influencing its final quality. A proteomic approach was used to evaluate changes in storage protein composition under water stress of two Italian durum wheat (Triticum turgidum ssp. durum) cultivars, Ciccio and Svevo. The high molecular-weight glutenin region increased progressively in both cultivars and under two water regimens. The L48-35 region, corresponding to low-molecular weight (LMW) glutenin subunits, increased slightly during grain development and decreased under water stress in both cultivars. In particular, an s-type LMW related to superior technological quality was down-expressed in the early-mid period in Svevo and in the mid-late period in Ciccio. Finally, the L<35 region, corresponding to gliadin-like proteins, decreased slightly during grain development and increased under stress in both cultivars. Several alpha-gliadins, associated with immunological potential, increased their expression under water stress, especially in Svevo in the early-mid stage of grain filling. PMID- 26138861 TI - Chiari II malformation. PMID- 26138862 TI - Chiari I malformation. PMID- 26138863 TI - A Molecular Platform for Multistate Near-Infrared Electrochromism and Flip-Flop, Flip-Flap-Flop, and Ternary Memory. AB - A diruthenium complex with a redox-active amine bridge has been designed, synthesized, and studied by single-crystal X-ray analysis and DFT and TDDFT calculations. It shows three well-separated redox processes with exclusive near infrared (NIR) absorbance at each redox state. The electropolymerized film of a related vinyl-functionalized complex displays multistate NIR electrochromism with low operational potential, good contrast ratio, and long retention time. Flip flop, flip-flap-flop, and ternary memories have been realized by using the obtained film (ca. 15-20 nm thick) with three electrochemical inputs and three NIR optical outputs that each displays three levels of signal intensity. PMID- 26138864 TI - Empagliflozin as Add-on Therapy to Pioglitazone With or Without Metformin in Patients With Type 2 Diabetes Mellitus. AB - PURPOSE: To investigate the long-term efficacy and safety of empagliflozin as add on therapy to pioglitazone with or without metformin in patients with type 2 diabetes mellitus. METHODS: Of 498 patients randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks in the EMPA-REG PIOTM study, 305 (61.2%) were treated in a double-blind extension trial for >=52 weeks (total duration >=76 weeks). Exploratory end points at week 76 included changes from baseline in glycosylated hemoglobin (HbA1c), weight, and blood pressure assessed using ANCOVA in patients who received >=1 dose of study drug and had a baseline HbA1c measurement in the initial study. FINDINGS: Compared with placebo, adjusted mean (95% CI) changes from baseline in HbA1c level at week 76 were 0.59% (-0.79% to -0.40%; P < 0.001) for empagliflozin 10 mg (-6.5 [-8.6 to -4.4] mmol/mol) and -0.69% (-0.88% to -0.50%; P < 0.001) for empagliflozin 25 mg (-7.5 [-9.6 to -5.4] mmol/mol). Compared with placebo, adjusted mean (95% CI) changes from baseline in weight at week 76 were -2.0 kg (-2.7 to -1.2 kg; P < 0.001) and 1.7 kg (-2.4 -1.0 kg; P < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, only empagliflozin 25 mg led to significant reductions in systolic blood pressure (adjusted mean [95% CI] change: -3.7 mmHg [-6.1 to -1.3 mmHg]; P = 0.003) and diastolic blood pressure (adjusted mean [95% CI] change: 2.2 mmHg [-3.7 to -0.7 mmHg]; P = 0.004). Sensitivity analyses were consistent with these results for HbA1c level, fasting plasma glucose concentration, and weight, but revealed no significant difference between empagliflozin and placebo in change from baseline in systolic or diastolic blood pressure at week 76. Confirmed hypoglycemic adverse events (glucose <=3.9 mmol/L and/or requiring assistance) were reported in 4.2%, 1.8%, and 3.0% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively; 1 patient each taking placebo and empagliflozin 25 mg required assistance. Adverse events consistent with urinary tract infection were reported in 26.7%, 22.4%, and 22.0% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Adverse events consistent with genital infection were reported in 3.0%, 10.3%, and 4.2% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. IMPLICATIONS: Empagliflozin 10 mg or 25 mg as add-on therapy to pioglitazone with or without metformin for 76 weeks was well tolerated and led to sustained reductions in HbA1c and weight compared with placebo in patients with type 2 diabetes. ClinicalTrials.gov identifier: NCT01210001. PMID- 26138865 TI - Pharmacokinetics and Pharmacodynamics of Twice Daily and Once Daily Regimens of Empagliflozin in Healthy Subjects. AB - PURPOSE: This study was undertaken to compare the steady-state pharmacokinetic and pharmacodynamic properties of empagliflozin 5 mg twice daily (BID) and 10 mg once daily (QD) in healthy subjects. METHODS: In an open-label, 2-way crossover study, subjects (n = 16) received empagliflozin 5 mg BID for 5 days and empagliflozin 10 mg QD for 5 days in a randomized order, with a washout period of >=6 days between each treatment. The primary objective was the comparison of the overall exposure during a 24-hour period at steady state (AUC0-24,ss) for empagliflozin, based on standard bioequivalence criteria, with BID and QD dose regimens. FINDINGS: The study population comprised 7 (43.8%) men and 9 (56.3%) women with a baseline median age of 38.0 years (range, 23-47 years) and a median body mass index of 23.3 kg/m(2) (range, 19.8-27.8 kg/m(2)). Based on standard bioequivalence criteria, there was no difference in the overall exposure of empagliflozin between BID and QD dose regimens (geometric mean ratio of AUC0 24,ss for empagliflozin 5 mg BID compared with empagliflozin 10 mg QD = 99.36%; 90% CI, 94.29-104.71). For empagliflozin 10 mg QD, mean (%CV) AUC during the dosing interval was 1900 nmol . h/L (20.6%), mean (%CV) Cmax,ss was 330 nmol/L (25.3%), and median (range) Tmax,ss was 1.0 hour (0.7-2.0 hours). For empagliflozin 5 mg BID, mean (%CV) AUC during the dosing interval was 1010 nmol . h/L (15.1%) and 867 nmol . h/L (18.6%) after the morning and evening dose, respectively, mean (%CV) Cmax,ss was 193 nmol/L (16.5%) and 120 nmol/L (21.0%), respectively, and median Tmax,ss was 1.0 hour (range, 0.7-2.0 hours) and 2.0 hours (range, 1.0-4.0 hours), respectively. The mean (%CV) cumulative amount of glucose excreted in urine during 24 hours was 52.1 g (32.1%) with empagliflozin 5 mg BID and 43.9 g (30.3%) with empagliflozin 10 mg QD. Adverse events were reported in six subjects (37.5%) receiving empagliflozin 5 mg BID and four (25.0%) receiving empagliflozin 10 mg QD. Headache was the most frequent AE. No severe, serious, or drug-related AEs were reported. IMPLICATIONS: There were no clinically relevant differences in pharmacokinetic or pharmacodynamic properties between BID and QD dose regimens of empagliflozin in healthy subjects. Both dose regimens were well tolerated. EU Clinical Trials Register (EudraCT) number: 2009 012524-90. PMID- 26138866 TI - Effect of Retosiban on Cardiac Repolarization in a Randomized, Placebo- and Positive-controlled, Crossover Thorough QT/QTc Study in Healthy Men and Women. AB - PURPOSE: Retosiban is a small molecule oxytocin receptor antagonist that is under evaluation in clinical studies for treatment of spontaneous preterm labor. A Thorough QT/QTc study was conducted to evaluate the effect of retosiban on cardiac repolarization according to International Conference on Harmonization E14 guidance. This was a randomized, placebo- and positive-controlled, single-dose, crossover study of healthy men and women. METHODS: All study participants received a 100 mg dose of retosiban (therapeutic target exposure), a 800 mg dose of retosiban (supratherapeutic target exposure), a 400 mg dose of moxifloxacin (positive control), and placebo with an appropriate washout. Holter monitoring data at baseline (predose) and at 13 subsequent time points during the next 24 hours were extracted and manually read by a central ECG reader who was blinded to the treatment assignment and corrected for heart rate by using the Fridericia formula (QTcF). A linear exposure-QTc response model was developed: DeltaDeltaQTcF=RI+Cp,R?RS+MI+Cp,M?MS, where RI and MI are intercept terms for retosiban and moxifloxacin, respectively, RS and MS are slope terms for retosiban and moxifloxacin, respectively, and Cp,R and Cp,M are plasma concentrations for retosiban and moxifloxacin, respectively. FINDINGS: A total of 52 healthy men (n = 27) and women (n = 25), with a mean age of 32 years, were enrolled in the study, and 43 (83%) completed all treatment periods and assessments. Mean placebo corrected change from baseline QT (DeltaDeltaQTcF) for the 2 retosiban dose groups revealed statistically significant decreases in DeltaDeltaQTcF between 2 and 3 hours after administration, reaching a value of -2.5 msec for both retosiban dose groups. The 400 mg moxifloxacin group had a statistically significant increase in the DeltaDeltaQTcF value at 0.75 hours after administration, reaching a maximal increase of 11.10 msec at 4 hours after administration. Results of the exposure-QTc response modeling revealed that there was no significant effect of retosiban on the DeltaDeltaQTcF at therapeutic exposures. For the supratherapeutic exposure of retosiban, there was a slight negative effect, with a mean decrease of -3.05 msec. The moxifloxacin arm had a mean increase in DeltaDeltaQTcF of 10.7 msec. IMPLICATIONS: At therapeutic and supratherapeutic exposures, retosiban had no significant effect on cardiac repolarization, as estimated by the DeltaDeltaQTcF. However, both doses of retosiban had a minor shortening effect. This is not considered to be clinically significant. CLINICALTRIALS. GOV IDENTIFIER: NCT01702376. PMID- 26138867 TI - Proof of Feasibility: What a Pilot Study Is and Is Not. PMID- 26138868 TI - Back to the Present. PMID- 26138869 TI - Intra-unit-cell magnetic correlations near optimal doping in YBa2Cu3O6.85. AB - The pseudo-gap phenomenon in copper oxide superconductors is central to any description of these materials as it prefigures the superconducting state itself. A magnetic intra-unit-cell order was found to occur just at the pseudo-gap temperature in four cuprate high-Tc superconducting families. Here we present polarized neutron-scattering measurements of nearly optimally doped YBa2Cu3O6.85, carried out on two different spectrometers, that reveal several features. The intra-unit-cell order consists of finite-sized planar domains that are very weakly correlated along the c axis. At high temperature, only the out-of-plane magnetic components correlate, indicating a strong Ising anisotropy. An aditional in-plane response develops at low temperature, giving rise to an apparent tilt of the magnetic moment. The discovery of these two regimes puts stringent constraints, which are tightly bound to the pseudo-gap physics, on the intrinsic nature of intra-unit-cell order. PMID- 26138870 TI - Inhibition of root meristem growth by cadmium involves nitric oxide-mediated repression of auxin accumulation and signalling in Arabidopsis. AB - The root is the first plant organ to get in contact with the toxin cadmium (Cd), which is a widespread soil contaminant. Cd inhibits the growth of the primary root, but the mechanisms underlying this inhibition remain elusive. In this study, we used physiological, pharmacological and genetic approaches to investigate the roles of nitric oxide (NO) and auxin in Cd-mediated inhibition of Arabidopsis thaliana root meristem growth. Our study demonstrated that in the first 12 h of exposure, Cd inhibits primary root elongation through a decrease in the sizes of both the elongation and meristematic zones. Following Cd exposure, a decrease in auxin levels is associated with reduced PIN1/3/7 protein accumulation, but not with reduced PIN1/3/7 transcript levels. Additionally, Cd stabilized AXR3/IAA17 protein to repress auxin signalling in this Cd-mediated process. Furthermore, decreasing Cd-induced NO accumulation with either NO specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3 oxide (cPTIO) or NO synthase inhibitor N(omega) -nitro-l-Arg-methylester (l-NAME) compromised the Cd-mediated inhibition of root meristem development, reduction in auxin and PIN1/3/7 accumulation, as well as stabilization of AXR3/IAA17, indicating that NO participates in Cd-mediated inhibition of root meristem growth. Taken together, our data suggest that Cd inhibits root meristem growth by NO-mediated repression of auxin accumulation and signalling in Arabidopsis. PMID- 26138871 TI - Dynamic Formation of Noncovalent Calixsalen Aggregates. AB - A procedure for studying "dynamic structural behavior" of large chiral macrocycles is presented. Ion mobility MS, diffusion-ordered NMR spectroscopy (DOSY NMR), and optical rotation (OR) measurements, supported by calculations, are used together as effective complementary methods to study dynamic formation of noncovalent aggregates. It is shown that the monomer-dimer equilibrium is driven by pi-pi or CH-pi interactions and controlled largely by the substitution pattern of the calixsalen skeleton. PMID- 26138872 TI - Breast Cancer Outcomes as Defined by the Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor-2 in a Multi-ethnic Asian Country. AB - INTRODUCTION: Breast cancer can be divided into four subtypes based on the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER2). Each subtype has different clinicopathological features and outcomes. OBJECTIVE: To compare the clinicopathological features and survival of ER and/or PR positive HER2 negative (ER+PR+HER2-, ER+PR-HER2- or ER PR+HER2-), ER and/or PR positive HER2 positive (ER+PR+HER2+, ER+PR-HER2+ or ER PR+HER2+), ER negative PR negative HER2 positive (ER-PR-HER2+), and ER negative PR negative HER2 negative (ER-PR-HER2-) subtypes. METHODS: 1957 patients with Stage 1-3 breast carcinoma diagnosed between Jan 2005 and Dec 2011 were categorized into the four subtypes. The clinicopathological features between the subtypes were compared using chi (2) test. Kaplan-Meier analysis was performed to estimate 5-year overall survival. Multivariate Cox regression was used to determine the association between subtypes and mortality adjusted for age, ethnicity, stage, pathological features, and treatment. RESULTS: ER-PR-HER2+ and ER-PR-HER2- subtypes were associated with younger age, larger tumors, and higher grade. There was no difference in the 5-year survival of the ER-PR-HER2+ and ER PR-HER2- subtypes (75.1 and 74.4 %, respectively) and survival was poorer than in the ER and/or PR positive HER2 negative and ER and/or PR positive HER2 positive subtypes (87.1 and 83.1 %, respectively). Only 9.5 % of women with HER2 positive breast cancer had access to trastuzumab. CONCLUSION: In a low resource setting with limited access to trastuzumab, there is no difference in survival between the ER-PR-HER2+ and ER-PR-HER2- subtypes of breast cancer. PMID- 26138873 TI - Central Venous Catheter-Related Infection in Severe Trauma Patients. AB - AIM: To evaluate the CVC-related infection rate according to catheter insertion site and to analyze the risk factors for catheter-related local infections (CRLI) and bloodstream infections (CRBSI) among severe trauma patients. METHODS: We reviewed the medical records of 736 severe trauma patients with an Injury Severity Score of >15. Poisson regression was used to compare the infection rates according to the catheter insertion sites. Univariate analysis of the groups with and without CVC-related infection was used to identify confounding variables for inclusion in multivariate models that were used to identify the risk factors for CRLI and CRBSI. RESULTS: We evaluated 1646 catheter insertions and their duration of insertion and found 1241 subclavian (18,461 days), 251 internal jugular (3454 days), and 154 femoral catheters (1526 days). The CRLI infection rate per 1000 catheter days was significantly lower for subclavian, compared to that for internal jugular (4.83 vs. 9.55, respectively; P < 0.001) and femoral catheters (4.83 vs. 7.93, respectively; P = 0.013). Multivariate logistic regression analysis revealed that catheter insertion duration [odds ratio (95 % confidence interval): 1.035 (1.021-1.050), P < 0.001] and subclavian access [0.532 (0.366 0.775), P < 0.001] were significantly associated with CRLI, while catheter insertion duration [1.024 (1.002-1.046), P = 0.032] was significantly associated with CRBSI. CONCLUSIONS: To reduce the rate of CVC-related infections in severe trauma patients, we suggest that catheters be shifted from the internal jugular or femoral veins to the subclavian vein as soon as possible and that the duration of catheter insertion should be minimized. PMID- 26138874 TI - Continuous Vagal Nerve Monitoring is Dangerous and Should not Routinely be Done During Thyroid Surgery. AB - INTRODUCTION: Laryngeal nerve monitoring has been increasingly embraced as a mechanism for mitigating the risk of nerve damage during thyroid and parathyroid surgery. Vagal nerve monitoring has recently been introduced as a potentially increased level of nerve integrity scrutiny. We sought to define the risks and benefits of this technology in a prospective analysis of a series of patients undergoing neck endocrine surgery. SETTING: High-volume academic endocrine surgery practice. METHODS: A prospective, non-controlled trial of continuous vagal nerve monitoring (CVNM) in a projected cohort of 20 non-randomly selected patients undergoing thyroid and parathyroid surgery was planned. A commercially available nerve monitoring system with automatic periodic stimulation was utilized for both laryngeal nerve monitoring and CVNM. Demographic data were obtained, and outcome variables included surgical procedures performed, pathology, complications, incremental time required to achieve CVNM, and benefits of monitoring and stimulation. RESULTS: The patient accrual was aborted after 9 surgeries (12 nerves monitored) because of two serious adverse events (hemodynamic instability and reversible vagal neuropraxia attributable to the monitoring apparatus). No other complications occurred. The time to establish monitoring ranged from 3 to 26 min, with a median of 6 min (representing 2.9-12.2 % of the total surgical procedural time). The stimulation clamp became dislodged 11 times in 5 cases and was replaced in 7 of those instances. Benefits of CVNM included recognition of reduced amplitude and increased nerve latency in two patients. CONCLUSIONS: We report the first evidence that CVNM may cause serious patient harm. This novel approach is invasive and threatens patient safety. Although it may occasionally provide meaningful information, the risk-benefit ratio does not favor widespread adoption. PMID- 26138875 TI - Transportability of confined field trial data from cultivation to import countries for environmental risk assessment of genetically modified crops. AB - Requirement of in-country confined field trials for genetically modified (GM) crops prior to unrestricted release is well-established among countries with domestic regulations for the cultivation approval of GM crops. However, the requirement of in-country confined field trials is not common in countries where the scope of the application does not include cultivation. Nonetheless, Japan and China request in-country confined field trials for GM crops which are intended only for use as food, feed and processing. This paper considers the transportability of confined field trial data from cultivation countries (e.g. United States, Canada, and South American countries) to import countries like Japan for the environmental risk assessment of GM crops by reviewing: (1) the purpose of confined field trial assessment, (2) weediness potential, defined as "an ability to establish and persist in an unmanaged area that is frequently disturbed by human activity", of host crops, and (3) reliability of the confined field trial data obtained from cultivation countries. To review the reliability of the confined field data obtained in the US, this paper describes actual examples of three confined field trials of approved GM corn events conducted both in the US and Japan. Based on the above considerations, this paper concludes that confined field data of GM corn and cotton is transportable from cultivation countries to importing countries (e.g. from the US to Japan), regardless of the characteristics of the inserted gene(s). In addition, this paper advocates harmonization of protocols for confined field trials to facilitate more efficient data transportability across different geographies. PMID- 26138876 TI - Increased production of wax esters in transgenic tobacco plants by expression of a fatty acid reductase:wax synthase gene fusion. AB - Wax esters are hydrophobic lipids consisting of a fatty acid moiety linked to a fatty alcohol with an ester bond. Plant-derived wax esters are today of particular concern for their potential as cost-effective and sustainable sources of lubricants. However, this aspect is hampered by the fact that the level of wax esters in plants generally is too low to allow commercial exploitation. To investigate whether wax ester biosynthesis can be increased in plants using transgenic approaches, we have here exploited a fusion between two bacterial genes together encoding a single wax ester-forming enzyme, and targeted the resulting protein to chloroplasts in stably transformed tobacco (Nicotiana benthamiana) plants. Compared to wild-type controls, transgenic plants showed both in leaves and stems a significant increase in the total level of wax esters, being eight-fold at the whole plant level. The profiles of fatty acid methyl ester and fatty alcohol in wax esters were related, and C16 and C18 molecules constituted predominant forms. Strong transformants displayed certain developmental aberrations, such as stunted growth and chlorotic leaves and stems. These negative effects were associated with an accumulation of fatty alcohols, suggesting that an adequate balance between formation and esterification of fatty alcohols is crucial for a high wax ester production. The results show that wax ester engineering in transgenic plants is feasible, and suggest that higher yields may become achieved in the near future. PMID- 26138877 TI - Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin/clavulanate. AB - The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values >= 4 during the hospital stay (P <= .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values >= 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR >= 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications. PMID- 26138878 TI - The Diagnostic Conundrum of Bronchopulmonary Dysplasia. PMID- 26138879 TI - Solitary Median Maxillary Central Incisor. PMID- 26138880 TI - Occurrence and distribution pattern of acidic pharmaceuticals in surface water, wastewater, and sediment of the Msunduzi River, Kwazulu-Natal, South Africa. AB - The paucity of information on the occurrence of pharmaceuticals in the environment in African countries led the authors to investigate 8 acidic pharmaceuticals (4 antipyretics, 3 antibiotics, and 1 lipid regulator) in wastewater, surface water, and sediments from the Msunduzi River in the province of KwaZulu-Natal, South Africa, using solid-phase extraction (SPE) and liquid chromatography-mass spectrometry (LC/MS). The method recoveries, limits of detection (LOD), and limits of quantification were determined. The method recoveries were 58.4% to 103%, and the LODs ranged between 1.16 ng/L and 29.1 ng/L for water and between 0.58 ng/g and 14.5 ng/g for sediment. The drugs were all present in wastewater and in most of the surface water and sediment samples. Aspirin was the most abundant pharmaceutical observed, 118 +/- 0.82 MUg/L in wastewater influent, and the most observed antibiotic was nalidixic acid (25.2 29.9 MUg/L in wastewater); bezafibrate was the least observed. The distribution pattern of the antipyretic in water indicates more impact in suburban sites. The solid-liquid partitioning of the pharmaceuticals between sediment and water, measured as the distribution coefficient (log KD ) gave an average accumulation magnitude of 10* to 32* in sediments than in water. The downstream distribution patterns for both water and sediment indicate discharge contributions from wastewater, agricultural activities, domestic waste disposal, and possible sewer system leakages. Although concentrations of the pharmaceuticals were comparable with those obtained from some other countries, the contamination of the present study site with pharmaceuticals has been over time and continues at present, making effective management and control necessary. PMID- 26138881 TI - EUS-Guided FNA for Diagnosis of Pancreatic Cystic Lesions: a Meta-Analysis. AB - BACKGROUND: Preoperative diagnosis of pancreatic cystic lesions (PCLs) must be reliable as the current standard treatment, major or total pancreatectomy, dramatically affects quality of life. Additionally, early diagnosis of malignancy is essential to an improved prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been demonstrated in pancreatic solid lesions. The utility of this technique in the diagnosis of PCLs is still unknown. METHODS: A comprehensive search was performed in multiple databases. Studies differentiating benign and malignant PCLs via EUS FNA were included in this meta-analysis. The quality of diagnostic accuracy studies (QUADAS) was adopted to evaluate the selected studies. Pooled sensitivity, specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic (sROC) curve analyses were conducted. Two main classification types of malignancy were characterized and analyzed. We also generated a subgroup analysis of available clinical factors. Publication bias was evaluated by Begg's and Egger's tests. RESULTS: Sixteen studies containing 1024 subjects have been published. The pooled sensitivity for malignant cytology according to classification 1 was 0.51 (95% CI, 0.45-0.58), and pooled specificity was 0.94 (95% CI, 0.92-0.96). When the detected PCLs were identified as classification 2, suspicious malignancy or potential malignancy, sensitivity and specificity were similar, 0.52 (95% CI, 0.46-0.57) and 0.97 (95% CI, 0.95 0.98) respectively. CONCLUSION: This meta-analysis demonstrates that EUS-FNA is a reliable clinical tool for the diagnosis of PCLs. However, a more accurate algorithm is needed to reduce various biases and to improve the sensitivity of EUS-FNA in the detection of malignant PCLs. PMID- 26138882 TI - Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways. AB - AIMS: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC) proliferation from a new point of view considering Connexin 43 (Cx43). METHODS: MC proliferation was measured by the incorporation of 3H thymidine (3H-TdR). Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT), and the intracellular calcium concentrations ([Ca(2+)]i) were characterized by confocal microscopy on cells loaded with Fura-3/AM. RESULTS: There was an inverse correlation between Cx43 expression and MC proliferation (P<0.05). SLDT studies revealed that there was no difference in the gap junction channel function between the normal and Aldosterone (Aldo)-stimulated groups (P>0.05). Our data also showed that the mineralcorticoid receptor (MR) antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca(2+)]i (P<0.05), suggesting that the classical PKC pathway might be activated. CONCLUSIONS: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways. PMID- 26138883 TI - Caveolin-1 Confers Resistance of Hepatoma Cells to Anoikis by Activating IGF-1 Pathway. AB - BACKGROUND/AIMS: Anoikis resistance is a prerequisite for hepatocellular carcinoma (HCC) metastasis. The role of Caveolin-1 (CAV1) in anoikis resistance of HCC remains unclear. METHODS: The oncogenic effect of CAV1 on anchor independent growth and anoikis resistance was investigated by overexpression and knockdown of CAV1 in hepatoma cells. IGF-1 pathway and its downstream signals were detected by immunoblot analysis. Caveolae invagination and IGF-1R internalization was studied by electron microscopy and (125)I-IGF1 internalization assay, respectively. The role of IGF-1R and tyrosine-14 residue (Y-14) of CAV1 was explored by deletion experiment and mutation experiment, respectively. The correlation of CAV1 and IGF-1R was further examined by immunochemical analysis in 120 HCC specimens. RESULTS: CAV1 could promote anchor independent growth and anoikis resistance in hepatoma cells. CAV1-overexpression increased the expression of IGF-1R and subsequently activated PI3K/Akt and RAF/MEK/ERK pathway, while CAV1 knockdown showed the opposite effect. The mechanism study revealed that CAV1 facilitated caveolae invagination and (125)I IGF1 internalization. IGF-1R deletion or Y-14 mutation reversed CAV1 mediated anchor-independent growth and anoikis resistance. In addition, CAV1 expression was positively related to IGF-1R expression in human HCC tissues. CONCLUSION: CAV1 confers resistance of hepatoma cells to anoikis by activating IGF-1 pathway, providing a potential therapeutic target for HCC metastasis. PMID- 26138884 TI - Regulation of Na+/H+ Exchanger in Dendritic Cells by Akt1. AB - BACKGROUND/AIMS: Dendritic cells (DCs), antigen-presenting cells critically important for primary immune response and establishment of immunological memory, are activated by bacterial lipopolysaccharides (LPS) resulting in stimulation of Na(+)/H(+) exchanger, ROS formation and migration. The effects are dependent on phosphoinositide 3 (PI3) kinase and paralleled by Akt phosphorylation. The present study explored the contribution of the Akt isoform Akt1. METHODS: Cytosolic pH (pH(i)) (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence), Na(+)/H(+) exchanger activity (Na(+) dependent realkalinization after an ammonium pulse), cell volume (forward scatter in FACS analysis), and ROS production (2',7'-dichlorodihydrofluorescein diacetate [DCFDA] fluorescence) were determined in DCs isolated from bone marrow of mice lacking functional Akt1/PKBalpha (akt1(-/-)) and their wild type littermates (akt1(+/+)). RESULTS: Forward scatter was lower in akt1(-/-) than in akt1(+/+) DCs, whereas pH(i), Na(+)/H(+) exchanger activity and ROS formation were less in untreated akt1(-/-) and akt1(+/+) DCs. Exposure of DCs to LPS was followed by increase of forward scatter and ROS formation to a similar extent in akt1(-/-) and in akt1(+/+) DCs. A 4 hours treatment with either LPS (1ug/ml) or tert butylhydroperoxide (tBOOH, 5 uM) significantly stimulated Na(+)/H(+) exchanger activity in both genotypes, effects, however, significantly blunted in akt1(-/-) DCs. CONCLUSION: The present observations demonstrate that Akt1 is required for the full stimulation of Na(+)/H(+) exchanger activity by LPS or oxidative stress in dendritic cells. PMID- 26138885 TI - Carbon Monoxide Inhibits Receptor Activator of NF-kappaB (RANKL)-Induced Osteoclastogenesis. AB - BACKGROUND: Low concentrations of carbon monoxide (CO) have anti-inflammatory effects and can reduce bone erosion in a murine collagen-induced arthritis model. The objective of this study was to assess the effects of CO on receptor activator of NF-kappaB ligand (RANKL), one of the key stimulators of osteoclastogenesis. METHODS: The in vivo effects of CO on RANKL expression were assessed in a collagen antibody-induced arthritis model in mice. Cell proliferation and apoptosis were assessed in the RAW246.7 cell line stimulated with RANKL and exposed to either air or CO. The number of tartrate resistant acid phosphatase (TRAP)-positive RAW246.7 cells was also examined after treatment with RANKL and the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, Troglitazone. RESULTS: CO reduced RANKL expression in the synovium of arthritic mice. Although CO slightly increased RAW246.7 cell proliferation, no differences in activated caspase 3 levels were detected. In addition, Troglitazone ameliorated the inhibitory effects of CO on RANKL-induced TRAP expression by RAW246.7 cells. CONCLUSIONS: CO suppresses osteoclast differentiation by inhibiting the RANKL-induced activation of PPAR-gamma. Given the role of the PPAR gamma/cFos (AP-1) pathway in regulating the transcription factor, NFATc1, the master regulator of osteoclastogenesis, further studies are warranted to explore CO in treating inflammatory bone disorders. PMID- 26138886 TI - Delayed in vitro development of Up states but normal network plasticity in Fragile X circuits. AB - A broad range of neurophysiological phenotypes have been reported since the generation of the first mouse model of Fragile X syndrome (FXS). However, it remains unclear which phenotypes are causally related to the cognitive deficits associated with FXS. Indeed, because many of these phenotypes are known to be modulated by experience, a confounding factor in the interpretation of many studies is whether some phenotypes are an indirect consequence of abnormal development and experience. To help diminish this confound we first conducted an in vitro developmental study of spontaneous neural dynamics in cortical organotypic cultures. A significant developmental increase in network activity and Up states was observed in both wild-type and Fmr1(-/y) circuits, along with a specific developmental delay in the emergence of Up states in knockout circuits. To determine whether Up state regulation is generally impaired in FXS circuits, we examined Up state plasticity using chronic optogenetic stimulation. Wild-type and Fmr1(-/y) stimulated circuits exhibited a significant decrease in overall spontaneous activity including Up state frequency; however, no significant effect of genotype was observed. These results demonstrate that developmental delays characteristic of FXS are recapitulated during in vitro development, and that Up state abnormalities are probably a direct consequence of the disease, and not an indirect consequence of abnormal experience. However, the fact that Fmr1(-/y) circuits exhibited normal homeostatic modulation of Up states suggests that these plasticity mechanisms are largely intact, and that some of the previously reported plasticity deficits could reflect abnormal experience or the engagement of compensatory mechanisms. PMID- 26138887 TI - EIMS Fragmentation Pathways and MRM Quantification of 7alpha/beta-Hydroxy Dehydroabietic Acid TMS Derivatives. AB - EI mass fragmentation pathways of TMS derivatives omicronf 7alpha/beta-hydroxy dehydroabietic acids resulting from NaBH(4)-reduction of oxidation products of dehydroabietic acid (a component of conifers) were investigated and deduced by a combination of (1) low energy CID-GC-MS/MS, (2) deuterium labeling, (3) different derivatization methods, and (4) GC-QTOF accurate mass measurements. Having identified the main fragmentation pathways, the TMS-derivatized 7alpha/beta hydroxy-dehydroabietic acids could be quantified in multiple reaction monitoring (MRM) mode in sea ice and sediment samples collected from the Arctic. These newly characterized transformation products of dehydroabietic acid constitute potential tracers of biotic and abiotic degradation of terrestrial higher plants in the environment. PMID- 26138888 TI - Risk of Damage to the Somatic Innervation of the Penis during the AdVanceProcedure: An Anatomical Study. AB - INTRODUCTION: One of the methods to treat post radical prostatectomy stress urinary incontinence is the AdVance (American Medical Systems, Minnetonka, MN, USA) male sling procedure. During this procedure, the somatic innervation of the penis may be at risk for injury. Six AdVance procedures were performed in six donated bodies at the Anatomy and Embryology Department of the Leiden University Medical Centre. The pelves were dissected and the shortest distance between the sling and the dorsal nerve of the penis (DNP) was documented. AIM: The aim of this study was to describe the anatomical relation between the AdVance male sling and penile nerves based on the dissection of six adult male pelves. METHODS: The AdVance male sling procedure was conducted in six donated male bodies. After placement, the pelves were dissected and the shortest distance between sling and the DNP was documented. MAIN OUTCOME MEASURE: The main outcome measure was the distance between the AdVance male sling and the DNP. RESULTS: The mean distance of the sling to the DNP was 4.1 mm and was found situated directly next to the nerve (distance 0 mm) in 4 out of 12 (33%) hemipelves. The distance of the sling to the obturator neurovascular bundle was 30 mm or more in all six bodies. CONCLUSIONS: Damage to the DNP caused by the AdVance male sling procedure appears to be an extremely rare complication, which has not been described in current literature. The proximity of the AdVance to the DNP could, however, pose a risk that should be taken into consideration by physicians and patients when opting for surgery. PMID- 26138889 TI - Erratum to: SPE and LC-MS/MS determination of 14 illicit drugs in surface waters from the Natural Park of L'Albufera (Valencia, Spain). PMID- 26138890 TI - Detection of bioavailable cadmium, lead, and arsenic in polluted soil by tailored multiple Escherichia coli whole-cell sensor set. AB - Microbial whole-cell sensor has been widely used to assess bioavailability and risk of toxic elements, but their environmental use is still limited due to the presence of other interfering pollutants and the nonspecific binding in cells, which leads to inaccurate results. Here, we proposed a strategy combining Escherichia coli sensor set with binary regression models for the specific detection of bioavailable cadmium (Cd), lead (Pb), and arsenic (As) in a co polluted environment. Initial tests suggested that the sensor set respectively termed pcadCluc, pzntRluc, and parsRluc could be classified into two groups according to their specific response to Cd, Pb, and As: group 1 (pcadCluc and pzntRluc) induced by a Cd-Pb mix and group 2 (parsRluc) induced by a Cd-As mix. Based on the variance in responses of each sensor to mixtures of target elements, three binary linear equations for two sensor groups were set up to calculate the individual concentrations in the mixture solutions. This method was then used to quantify the bioavailable Cd, Pb, and As in soils from a co-polluted mining region and to compare the results with other methods. Results showed that the conventional single target sensor method overestimated the bioavailability of each element, while sensor set was credible for accurate bioavailable Cd, Pb, and As quantification and comparable with the results from inductively coupled plasma mass spectrometry (ICP-MS) analysis. Our method can potentially be extended to cover the specific detection of other bioavailable toxic elements in different environmental settings. PMID- 26138891 TI - Development of certified matrix-based reference material of genetically modified rice event TT51-1 for real-time PCR quantification. AB - In 2009, the genetically modified (GM) rice event TT51-1 with an engineered insect resistance trait became the first GM rice event to be granted certification for safe production in China, and its derivative lines Bt 63 and Huahui No.1 are expected to be commercialized soon. The development of certified reference material (CRM) for TT51-1 is necessary to monitor and inspect the TT51 1 event and its derivates. In this work, we developed four matrix-based TT51-1 rice CRMs (TT51-1a, TT51-1b, TT51-1c, and TT51-1d) with different TT51-1 mass fraction ratios by blending seed powders of homozygous TT51-1 and its recipient cultivar Minghui 63. The between-bottle homogeneity and the within-bottle homogeneity were tested, and good results were obtained. The potential degradation during transportation and shelf life were evaluated, and demonstrated an expiration period of at least 36 months. The characterization values of the four TT51-1 CRMs based on the mass fraction ratio were 1000.000 +/- 51.430 g/kg, 49.940 +/- 4.620 g/kg, 9.990 +/- 1.110 g/kg, and 4.990 +/- 0.620 g/kg, respectively. The characterization values based on the copy number ratio were certified by digital PCR analysis as 97.442 +/- 5.253 %, 4.851 +/- 0.486 %, 1.042 +/- 0.135 %, and 0.556 +/- 0.073 %, respectively. These results suggested that the TT51-1 matrix-based CRMs developed are of high quality and can be used as potential calibrators for TT51-1 GM rice inspection and monitoring. PMID- 26138892 TI - UPLC-ESI-Q-TOF-MS(E) and GC-MS identification and quantification of non intentionally added substances coming from biodegradable food packaging. AB - Biodegradable packagings are made by combination of several materials creating a multilayer with the properties needed. Each material, including the adhesive, could contain substances that could migrate to the food. In this work, gas chromatography coupled with mass spectrometry and ultra-high-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were used to identify the biodegradable adhesive compounds. Five of the 13 compounds identified were nonintentionally added substances; they were neoformed compounds created by the reaction of added compounds in the adhesive. Moreover, the migration of the compounds through four different biodegradable materials-paper, polylactic acid, ecovio(r), and polyvinyl alcohol-was studied for the first time. Three of the 13 compounds identified in the adhesive migrated from the adhesive to Tenax(r), which was used as a solid food simulant. One of them, 2,4,7,9 tetramethyl-5-decyne-4,7-diol, was an intentionally added substance, and the other two were 1,6-dioxacyclododecane-7,12-dione and 1,6,13,18 tetraoxacyclotetracosane-7,12,19,24-tetraone, which were nonintentionally added substances identified in this work. Higher migration values (ranging from 0.81 to 2.07 mg/kg) were observed for migration through ecovio(r) than through the multilayer made by combination of ecovio(r) and polyvinyl alcohol (0.07-0.39 mg/kg) owing to the barrier effect provided by polyvinyl alcohol. The migration values for migration through paper and polylactic acid were below the limits of detection. PMID- 26138893 TI - Advances in liquid chromatography-high-resolution mass spectrometry for quantitative and qualitative environmental analysis. AB - This review summarizes the advances in environmental analysis by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) during the last decade and discusses different aspects of their application. LC-HRMS has become a powerful tool for simultaneous quantitative and qualitative analysis of organic pollutants, enabling their quantitation and the search for metabolites and transformation products or the detection of unknown compounds. LC-HRMS provides more information than low-resolution (LR) MS for each sample because it can accurately determine the mass of the molecular ion and its fragment ions if it can be used for MS-MS. Another advantage is that the data can be processed using either target analysis, suspect screening, retrospective analysis, or non-target screening. With the growing popularity and acceptance of HRMS analysis, current guidelines for compound confirmation need to be revised for quantitative and qualitative purposes. Furthermore, new commercial software and user-built libraries are required to mine data in an efficient and comprehensive way. The scope of this critical review is not to provide a comprehensive overview of the many studies performed with LC-HRMS in the field of environmental analysis, but to reveal its advantages and limitations using different workflows. PMID- 26138894 TI - Quantification of free polyamines and their metabolites in biofluids and liver tissue by UHPLC-MS/MS: application to identify the potential biomarkers of hepatocellular carcinoma. AB - Polyamines and their N-acetylated metabolites are potential biomarkers in the diagnosis and therapeutic evaluation of cancer. Thus, we present here an ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of 6 free, 3 monoacetylated, and 2 diacetylated polyamines without derivatization. The major improvement of this method is the use of 0.2 % perfluoroheptanoic acid methanol in the pretreatment step to achieve protein precipitation and 0.0125 % perfluoroheptanoic acid in the mobile phase to achieve analyte separation within 9 min. The established analytical method was validated with plasma, urine, and liver tissue and applied to determine plasma, urine, and liver tissue samples from healthy rats, hepatocellular carcinoma rats, and administrated rats successfully. Results indicated free polyamines such as putrescine mainly existed in liver tissue but more polar N-acetylated metabolites such as N (1),N (12)-diacetylspermine seemed to exist in biological fluid. After carcinogenesis, the levels of polyamines were increased, but the elevated levels of polyamines and their metabolites tended to decrease when administrated with anticancer drug. The method provided a more versatile manner for clinical application in the diagnosis and therapeutic evaluation of hepatocellular carcinoma. PMID- 26138895 TI - High-resolution elemental mapping of human placental chorionic villi using synchrotron X-ray fluorescence spectroscopy. AB - The placenta is the organ that mediates transport of nutrients and waste materials between mother and fetus. Synchrotron X-ray fluorescence (SXRF) microanalysis is a tool for imaging the distribution and quantity of elements in biological tissue, which can be used to study metal transport across biological membranes. Our aims were to pilot placental biopsy specimen preparation techniques that could be integrated into an ongoing epidemiology birth cohort study without harming rates of sample acquisition. We studied the effects of fixative (formalin or glutaraldehyde) and storage duration (30 days or immediate processing) on metal distribution and abundance and investigated a thaw-fixation protocol for archived specimens stored at -80 degrees C. We measured fixative elemental composition with and without a placental biopsy via inductively coupled plasma mass spectrometry (ICP-MS) to quantify fixative-induced elemental changes. Formalin-fixed specimens showed hemolysis of erythrocytes. The glutaraldehyde paraformaldehyde solution in HEPES buffer (GTA-HEPES) had superior anatomical preservation, avoided hemolysis, and minimized elemental loss, although some cross-linking of exogenous Zn was evident. Elemental loss from tissue stored in fixative for 1 month showed variable losses (~40 % with GTA-HEPES), suggesting storage duration be controlled for. Thawing of tissue held at -80 degrees C in a GTA-HEPES solution provided high-quality visual images and elemental images. PMID- 26138896 TI - Clinical features and course of cutaneous mastocytosis in 133 children. PMID- 26138897 TI - Lung ultrasound in the diagnosis and monitoring of community acquired pneumonia in children. AB - Lung ultrasound (LUS) is as an easily accessible, radiation-free imaging technique that might be used as a diagnostic tool in community-acquired pneumonia (CAP). The aim of the study was to evaluate the usefulness and accuracy of LUS in the diagnosis and monitoring of childhood CAP. One hundred six consecutive children aged between 1 and 213 (median 52.5) months referred to the hospital with suspicion of CAP were enrolled. All patients underwent LUS on the day of admission, followed by chest radiograph (CXR). Lung ultrasound was also performed in 25 children between 5th-7th and 31 children between 10th-14th day after admission. Radiographic signs of pneumonia were demonstrated in 76 children, while lung ultrasound revealed pulmonary abnormalities consistent with pneumonia in 71 children. LUS gave false negative results in 5 patients with parahilar pulmonary infiltrates demonstrated by CXR. Almost perfect overall agreement between LUS and CXR was found in terms of pneumonia diagnosis (Cohen kappa coefficient of 0.89). The diagnostic performance of LUS in demonstration of lung involvement was as follows: sensitivity of 93.4%, specificity of 100%, positive predictive value of 100%, negative predictive value of 85.7% and accuracy of 95.3%. Our study showed that LUS is a sensitive and highly specific diagnostic method in children with CAP. Therefore, LUS may be considered as the first imaging test in children with suspicion of CAP. A diagnostic algorithm of CAP which includes LUS should be validated in prospective studies. Lung ultrasound can also be used to follow-up resolution of pneumonic lesions. PMID- 26138898 TI - A comparison of younger and older men who have sex with men using data from Jamaica AIDS Support for Life: characteristics associated with HIV status. AB - Jamaica is home to over 10% of the Caribbean's HIV-positive population. Men who have sex with men (MSM) have a higher prevalence of HIV compared to the general public. Thus, the purpose of this study is to assess characteristics associated with HIV, such as condom use and number of sexual partners, comparing young, those aged 18-24, to older, aged 25 and older, MSM in Jamaica. We hypothesised, and found support for the notion, that younger MSM would have a lower rate of some risky behaviours associated with HIV seropositivity. Service data for 160 self-selected MSM aged 18-62, from Kingston, Jamaica were analysed. The majority identified as homosexual (compared to bisexual), over half of respondents completed a tertiary level of education (e.g. any post-high school training), and 59.1% were employed. Almost all participants reported agreeing to use a condom when requested (93.6%). Prevalence of HIV was 17.8%, much lower than the 32% found in national studies, and is likely an underestimation reflecting patterns of this self-selected sample. Additionally, over one-third reported experiencing sexual abuse. Statistically significant relationships were found between age group and tertiary education, employment status, condom use with a regular partner, and sexual abuse. Younger MSM were more likely to have been sexually abused and were more likely to always wear a condom with their regular partner. A limitation of this study was the extent of missing data, restricting generalisability. However, by acknowledging the heterogeneity of the Jamaican MSM population, and subsequently evaluating behaviours across age groups, nuances emerge which highlight behavioural diversity. Findings may inform public health practitioners in developing targeted interventions. PMID- 26138899 TI - The generational effect on age disparate partnerships and the risk for human immunodeficiency virus and sexually transmitted infections acquisition. AB - In South Africa, a large proportion of young women are in age disparate relationships, which is believed to be a risk factor for human immunodeficiency virus (HIV). The aim of this study was to determine the generational effect of age disparity on HIV and sexually transmitted infection (STI) incidence. Socio demographic and behavioural data were collected from women, aged 16 and older, who were followed for up to 24 months. Women who reported having a steady sexual partner older than themselves were categorised into: (1) non-age disparate partnerships (age difference between partners was 0-4 years); (2) intra generational age disparate partnerships (5-9 year age gap between sexual partners); and (3) inter-generational age disparate partnerships (age gap of 10 years or more between sexual partners). Of the 1355 women included in the analysis, 759, 429 and 167 were in non-age disparate, intra-generational age disparate and inter-generational age disparate partnerships, respectively. Strong predictors of inter-generational age disparate partnerships include age, marital status and concurrency of sexual partners. No significant relationship between age disparity and risk of HIV acquisition was found. The highest crude STI incidence was observed among those in intra-generational age disparate relationships followed by those in non-age disparate relationships (31.86 [26.41 38.44] and 25.60 [21.92-29.91] per 100 person-years, respectively). Reduction of multiple partnerships remains key to HIV prevention; however, in light of partner concurrency being more prevalent than individual concurrency partnerships, female initiated HIV prevention options remain critical. PMID- 26138900 TI - Long-term seroprotective response of trivalent seasonal influenza vaccine in HIV infected children, regardless of immunogenicity before immunisation. AB - Influenza vaccination can reduce disease in HIV-infected children. The durability of the antibody response after trivalent influenza vaccine is important for management. The aim of this prospective study was to assess the durability of seroprotection for trivalent influenza vaccine strains and the factors effecting seroprotective response regardless of immunogenicity before trivalent influenza vaccine at one and six months after immunisation. Hemagglutination inhibition assay was done at one and six months. Seventy-five HIV-infected children were enrolled after vaccination. Four children were lost to follow-up. None of the children had confirmed influenza infection between immunisation and hemagglutination inhibition at six months after influenza vaccination. Seventy one children were included in the final analysis and immunogenicity of trivalent influenza vaccine strains at one and six months. Of these, 27 (38%) had complete seroprotection (Group A) and 44 (62%) had non-complete seroprotection (Group B). Sex, age and the body mass index of both groups were not different from each other (p > 0.05). There was a higher mean CD4 level and more children with RNA <=40 copies/mL among Group A compared with Group B (p < 0.05). Other factors did not differ significantly. The durability of the seroprotective response after trivalent influenza vaccine was associated with a high CD4 level and virological suppression before vaccination. PMID- 26138901 TI - Review: basics of drug development in rheumatology. PMID- 26138902 TI - Guideline-concordant timely lung cancer care and prognosis among elderly patients in the United States: A population-based study. AB - OBJECTIVES: Elderly carry a disproportionate burden of lung cancer in the US. Therefore, its important to ensure that these patients receive quality cancer care. Timeliness of care is an important dimension of cancer care quality but its impact on prognosis remains to be explored. This study evaluates the variations in guideline-concordant timely lung cancer care and prognosis among elderly in the US. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2002-2007), we identified elderly patients with lung cancer (n=48,850) and determined time to diagnosis and treatment. We categorized patients by receipt of timely care using guidelines from the British Thoracic Society and the RAND Corporation. Hierarchical generalized logistic model was constructed to identify variables associated with receipt of timely care. Kaplan-Meier analysis and Log Rank test was used for estimation and comparison of the three-year survival. Multivariable Cox proportional hazards model was constructed to estimate lung cancer mortality risk associated with receipt of delayed care. RESULTS: Time to diagnosis and treatment varied significantly among the elderly. However, majority of them (77.5%) received guideline-concordant timely lung cancer care. The likelihood of receiving timely care significantly decreased with NSCLC disease, early stage diagnosis, increasing age, non-white race, higher comorbidity score, and lower income. Paradoxically, survival outcomes were significantly worse among patients receiving timely care. Adjusted lung cancer mortality risk was also significantly lower among patients receiving delayed care, relative to those receiving timely care (Hazard ratio (HR)=0.68, 95% Confidence interval (CI)=(0.66-0.71); p <= 0.05). CONCLUSION: This study highlights the critical need to address disparities in receipt of guideline-concordant timely lung cancer care among elderly. Although timely care was not associated with better prognosis in this study, any delays in diagnosis and treatment should be avoided, as it may increase the risk of disease progression and psychological stress in patients. Furthermore, given that lung cancer diagnostic and management services are covered under the Medicare program, observed delays in care among Medicare beneficiaries is also a cause for concern. PMID- 26138904 TI - Investigation of pharmaceuticals, personal care products and endocrine disrupting chemicals in a tropical urban catchment and the influence of environmental factors. AB - Previous studies showed the presence of multiple emerging organic contaminants (EOCs) in urban surface waters of Singapore even though there are no obvious direct wastewater discharges. In this study, we investigated the occurrence and distribution of 17 pharmaceuticals and personal care products (PPCPs) and endocrine disruptive compounds (EDCs) in a tropical urban catchment of Singapore. Monthly samples were collected from a reservoir and its 5 upstream tributaries during a 16-month period. Analysis of samples showed all sites had measurable PPCP and EDC concentrations, with caffeine (33.9-2980 ng/L), salicylic acid (5 838 ng/L), acetaminophen (<4-485.5 ng/L), BPA (<2-919.5 ng/L) and DEET (13-270 ng/L) being the most abundant. Marked differences in concentrations of target analytes between the reservoir and upstream tributaries were observed, and were tentatively attributed to the spatial differences in source inputs, water dilution capacity as well as natural attenuation of EOCs. Significant correlations between EOCs and conductivity, dissolved oxygen, chlorophyll a, turbidity, nutrients and cumulative precipitation were observed. These factors appeared to affect the distribution and attenuation of EOCs, depending on their physicochemical properties. Rainfall also influenced the temporal distribution of caffeine, BPA, triclosan, fipronil and DEET in the reservoir. Ecological risk assessment showed that caffeine, acetaminophen, estrone, BPA, triclosan and fipronil may warrant further survey. In particular, BPA levels exceeded the literature-based Predicted No-Effect Concentration (PNEC) value, highlighting the need for source control and/or water remediation in this urban catchment. PMID- 26138903 TI - Honokiol ameliorates endothelial dysfunction through suppression of PTX3 expression, a key mediator of IKK/IkappaB/NF-kappaB, in atherosclerotic cell model. AB - Pentraxin 3 (PTX3) was identified as a marker of the inflammatory response and overexpressed in various tissues and cells related to cardiovascular disease. Honokiol, an active component isolated from the Chinese medicinal herb Magnolia officinalis, was shown to have a variety of pharmacological activities. In the present study, we aimed to investigate the effects of honokiol on palmitic acid (PA)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and to elucidate potential regulatory mechanisms in this atherosclerotic cell model. Our results showed that PA significantly accelerated the expression of PTX3 in HUVECs through the IkappaB kinase (IKK)/IkappaB/nuclear factor-kappaB (NF-kappaB) pathway, reduced cell viability, induced cell apoptosis and triggered the inflammatory response. Knockdown of PTX3 supported cell growth and prevented apoptosis by blocking PA-inducted nitric oxide (NO) overproduction. Honokiol significantly suppressed the overexpression of PTX3 in PA-inducted HUVECs by inhibiting IkappaB phosphorylation and the expression of two NF-kappaB subunits (p50 and p65) in the IKK/IkappaB/NF-kappaB signaling pathway. Furthermore, honokiol reduced endothelial cell injury and apoptosis by regulating the expression of inducible NO synthase and endothelial NO synthase, as well as the generation of NO. Honokiol showed an anti-inflammatory effect in PA-inducted HUVECs by significantly inhibiting the generation of interleukin-6 (IL-6), IL-8 and monocyte chemoattractant protein-1. In summary, honokiol repaired endothelial dysfunction by suppressing PTX3 overexpression in an atherosclerotic cell model. PTX3 may be a potential therapeutic target for atherosclerosis. PMID- 26138906 TI - Programmed assembly of 4,2':6',4''-terpyridine derivatives into porous, on surface networks. AB - The use of divergent, V-shaped, 4,2':6',4''-terpyridine building blocks that self assemble into hydrogen-bonded domains and upon addition of copper atoms undergo metallation with concomitant transformation into a coordination network is described; multiple energetically similar structural motifs are observed in both hydrogen-bonded and adatom-coordinated networks. PMID- 26138905 TI - Transient myeloproliferative disorder with partial trisomy 21. AB - Myeloid malignancy with Down syndrome (ML-DS) is estimated to have a step-wise leukemogenesis including GATA1 mutation. Trisomy 21 is essential for ML-DS; however, we do not know exactly which gene or genes located on chromosome 21 are necessary for the ML-DS. We report a female infant with transient myeloproliferative disorder (TMD) and partial trisomy 21. SNP array analysis showed 10 Mb amplification of 21q22.12-21q22.3, which included DYRK1A, ERG, and ETS but not the RUNX1 gene. With two other reported TMD cases having partial trisomy 21, DYRK1A, ERG, and ETS were the most likely genes involved in collaboration with the GATA1 mutation. PMID- 26138907 TI - Mechanical clearance of red blood cells by the human spleen: Potential therapeutic applications of a biomimetic RBC filtration method. AB - During their lifespan, circulating RBC are frequently checked for their deformability. This mechanical quality control operates essentially in the human spleen. RBC unable to squeeze though narrow splenic slits are retained and cleared from the blood circulation. Under physiological conditions this prevents microvessels from being clogged by senescent, rigid RBC. Retention of poorly deformable RBC is an important determinant of pathogenesis in malaria and may also impact the clinical benefit of transfusion. Modulating the splenic retention of RBC has already been proposed to support therapeutic approaches in these research fields. To this aim, the development of microplates for high throughput filtration of RBC through microsphere layers (microplate-based microsphiltration) has been undertaken. This review focuses on potential therapeutic applications provided by this technology in malaria chemotherapy and transfusion. PMID- 26138909 TI - Evaluation of migraine in patients with ischaemic stroke. AB - An association between migraine and ischaemic stroke has been observed for many years, but the exact mechanisms by which migraine can lead to stroke are still unknown. The purpose of this study was to determine the prevalence of migraine headaches in patients with ischaemic stroke. In this prospective cohort study, we assessed 323 patients with ischaemic stroke; these diagnoses were assigned based on the International Headache Society criteria for migraine with or without aura. Patients were recruited without major risk factors such as stroke, hypertension, hyperlipidaemia, diabetes, taking oral contraceptive pills, history of drug abuse and trauma in issue of their Stroke. Data were collected via a written questionnaire upon admission and were analysed with SPSS version 16 software. Comparisons were performed using Mann-Whitney's U test and chi-square and t-test. Migraine headache was present in 11.2% (36 of 323) of patients, 8.1% of women and 3.1% of men. Migraine prevalence was highest in the age over 60 years. There was a history of migraine without aura for over 2 years in 6.2% of patients with ischaemic stroke. Also, we found no significant correlation between migraine headache and location of the lesion in patients with ischaemic stroke. PMID- 26138908 TI - High-resolution NMR characterization of low abundance oligomers of amyloid-beta without purification. AB - Alzheimer's disease is characterized by the misfolding and self-assembly of the amyloidogenic protein amyloid-beta (Abeta). The aggregation of Abeta leads to diverse oligomeric states, each of which may be potential targets for intervention. Obtaining insight into Abeta oligomers at the atomic level has been a major challenge to most techniques. Here, we use magic angle spinning recoupling (1)H-(1)H NMR experiments to overcome many of these limitations. Using (1)H-(1)H dipolar couplings as a NMR spectral filter to remove both high and low molecular weight species, we provide atomic-level characterization of a non fibrillar aggregation product of the Abeta1-40 peptide using non-frozen samples without isotopic labeling. Importantly, this spectral filter allows the detection of the specific oligomer signal without a separate purification procedure. In comparison to other solid-state NMR techniques, the experiment is extraordinarily selective and sensitive. A resolved 2D spectra could be acquired of a small population of oligomers (6 micrograms, 7% of the total) amongst a much larger population of monomers and fibers (93% of the total). By coupling real-time (1)H (1)H NMR experiments with other biophysical measurements, we show that a stable, primarily disordered Abeta1-40 oligomer 5-15 nm in diameter can form and coexist in parallel with the well-known cross-beta-sheet fibrils. PMID- 26138910 TI - Autologous and allogeneic serum eye drops. The Dutch perspective. AB - If regular artificial tears are ineffective for treatment of ocular surface disorders (including extreme dry eye syndrome), serum eye drops (SEDs) may provide a way to relieve the symptoms. However, not all patients are eligible to donate blood to produce autologous SEDs. Therefore, the use of allogeneic SEDs (obtained from voluntary blood donors) should be explored as an alternative for autologous SEDs. The Dutch blood bank organization is currently looking into the possibilities to provide allogeneic SEDs, as (GMP) regulations become stricter, making it for hospitals more difficult to provide autologous SEDs. To demonstrate effectiveness of both autologous and allogeneic SEDs, a clinical trial is planned. The current status of SEDs in The Netherlands is described. This paper is based on summary of the presentation given at the DGTI meeting in Dresden. PMID- 26138911 TI - Hepatitis C: Prevalence of serologic markers and risk factors in blood donors at a large blood centre in South-eastern Brazil (2007-2010). AB - This study aimed to evaluate the trends of HCV seropositivity rates in first time blood donors from a reference blood centre in Southeast Brazil. Data from the period of 2007-2010 were analysed according to anti-HCV antibodies, donor demographic characteristics and type of donation. There was a marked and continuous decline in prevalence in the analysed period, and in 93,534 first time donors, the prevalence of anti-HCV was 0.09%. Anti-HCV were associated with less education and older age (>= 35 years). The rates of anti-HCV observed in the present study were lower than in Brazil, but considerably higher than developed countries. PMID- 26138912 TI - Predicting Overall Survival After Stereotactic Ablative Radiation Therapy in Early-Stage Lung Cancer: Development and External Validation of the Amsterdam Prognostic Model. AB - PURPOSE: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA selected factors to evaluate their relationship with OS. A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n = 193) and SABR (n = 543) datasets. RESULTS: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r(2) = 0.97) and external SABR (r(2) = 0.79) and surgical cohorts (r(2) = 0.91). CONCLUSIONS: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities. PMID- 26138913 TI - Indian hospital's insensitive treatment of woman with HIV is condemned. PMID- 26138915 TI - The Solitary Pulmonary Nodule. AB - Due to the high etiological diversity and the potential for malignancy, pulmonary nodules represent a clinical challenge, becoming increasingly frequent as the number of CT examinations rises. The topic gains even more importance as clear evidence for the effectiveness of CT screening was provided by the National Lung Screening Trial (NLST). Yet, the results were tempered by the high false-positive rate and the requirement of performing further diagnostic procedures. The management of those detected solitary pulmonary nodules is currently based on the individuals' risk of developing lung cancer, the pulmonary nodule characteristics and the capability of diagnostic and therapeutic approaches. PMID- 26138914 TI - Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities. AB - RNA helicases are implicated in most cellular RNA-dependent events. In eukaryotes however, only few have been functionally characterized. Upf1 is a RNA helicase essential for nonsense-mediated mRNA decay (NMD). Here, using magnetic tweezers and bulk assays, we observe that human Upf1 is able to translocate slowly over long single-stranded nucleic acids with a processivity >10 kb. Upf1 efficiently translocates through double-stranded structures and protein-bound sequences, demonstrating that Upf1 is an efficient ribonucleoprotein complex remodeler. Our observation of processive unwinding by an eukaryotic RNA helicase reveals that Upf1, once recruited onto NMD mRNA targets, can scan the entire transcript to irreversibly remodel the mRNP, facilitating its degradation by the NMD machinery. PMID- 26138917 TI - Factors Affecting the Choice and Desire to Exclusively Breastfeed in Jamaica: A Cross-Sectional Study at 6 Weeks Postpartum. AB - BACKGROUND: Exclusive breastfeeding rates (EBRs) may be influenced by sociodemographic and sociocultural factors, including maternal age, socioeconomic status, education, and breastfeeding knowledge. The EBR in Jamaica has been low and declining, leaving a need for better determination of the specific local contributory factors. OBJECTIVES: This study aimed to better elucidate the factors that influence mothers exclusively breastfeeding, including antenatal intentions to breastfeed, mothers' knowledge of the benefits of breastfeeding, and mothers' infant feeding practices in general, inclusive of breastfeeding, formula feeding, and complementary feeding. METHODS: A cross-sectional survey was conducted using a 52-item interviewer-administered questionnaire with mothers attending their 6-week postnatal clinic visit. Sociodemographic data were collected on all participants as well as data regarding participants' breastfeeding knowledge, attitudes, and practices. Statistical analyses were done using chi(2) tests, t tests, and risk analyses. RESULTS: Two hundred participants were interviewed; the mean +/- SD age of participants was 26.2 +/- 6.46 years (range, 15-46 years). The EBR in this study sample was 32%. Sociodemographic factors, including maternal age and socioeconomic status, as well as antenatal and postnatal breastfeeding sessions, did not significantly affect the likelihood of exclusively breastfeeding at 6 weeks postpartum. The only factor significantly associated with the EBR was mothers' belief that exclusively breastfeeding was able to ensure infant satiety. CONCLUSION: Antenatal and postnatal breastfeeding sessions should place more emphasis on dispelling maternal myths and misperceptions regarding signs of satiety and hunger in infants and reinforcing the knowledge that breast milk alone is sufficient for the first 6 months of life. PMID- 26138918 TI - Editorial review: an update on central sensitivity syndromes and the issues of nosology and psychobiology. AB - Central sensitization (CS), simply defined as an amplified response of the central nervous system to peripheral input, is a concept of great importance in clinical medicine. It has helped to explain aspects of the pathophysiology of common diseases, e.g. fibromyalgia syndrome (FMS), irritable bowel syndrome, vulvodynia, headaches, chronic pelvic pain and other overlapping conditions (collectively called central sensitivity syndromes, or CSS). It also applies to pain of complex regional pain syndrome, osteoarthritis (OA), rheumatoid arthritis (RA) and post-operative pain. The pathology-pain gap in CSS is readily explained by CS. Many FMS and other CSS patients have peripheral pathology, e.g. nociceptive areas in the muscles, arthritis, small fiber neuropathy and inflammation. Pro-inflammatory cytokines are elevated in some patients. Identification of CS in patients with structural pathology, e.g. OA and RA, has helped to explain why not all patients benefit from nonsteroidal anti inflammatory drugs or joint replacement surgery, and require therapy directed at CS. Glial cells are important in pain processing. Remarkable advances have been achieved in neuroimaging, including visualization of grey matter and white matter, not only during provoked pain but also pain at rest. Based on CS mechanisms, targeted individual therapy may now be possible. Appropriate nosology is important particularly for effective patient care. Dichotomy of neurochemical structural ("functional") and structural ("organic") pathology should be abandoned; many patients have both. Psychobiology is also biology. Patient blaming terms like somatization, somatizer and catastrophizing should be avoided. For therapy, both pharmacological and non- pharmacological approaches are important, including recognition of subgroups and person/patient-centered care. PMID- 26138916 TI - Carotenoid biosynthetic genes in Brassica rapa: comparative genomic analysis, phylogenetic analysis, and expression profiling. AB - BACKGROUND: Carotenoids are isoprenoid compounds synthesized by all photosynthetic organisms. Despite much research on carotenoid biosynthesis in the model plant Arabidopsis thaliana, there is a lack of information on the carotenoid pathway in Brassica rapa. To better understand its carotenoid biosynthetic pathway, we performed a systematic analysis of carotenoid biosynthetic genes at the genome level in B. rapa. RESULTS: We identified 67 carotenoid biosynthetic genes in B. rapa, which were orthologs of the 47 carotenoid genes in A. thaliana. A high level of synteny was observed for carotenoid biosynthetic genes between A. thaliana and B. rapa. Out of 47 carotenoid biosynthetic genes in A. thaliana, 46 were successfully mapped to the 10 B. rapa chromosomes, and most of the genes retained more than one copy in B. rapa. The gene expansion was caused by the whole-genome triplication (WGT) event experienced by Brassica species. An expression analysis of the carotenoid biosynthetic genes suggested that their expression levels differed in root, stem, leaf, flower, callus, and silique tissues. Additionally, the paralogs of each carotenoid biosynthetic gene, which were generated from the WGT in B. rapa, showed significantly different expression levels among tissues, suggesting differentiated functions for these multi-copy genes in the carotenoid pathway. CONCLUSIONS: This first systematic study of carotenoid biosynthetic genes in B. rapa provides insights into the carotenoid metabolic mechanisms of Brassica crops. In addition, a better understanding of carotenoid biosynthetic genes in B. rapa will contribute to the development of conventional and transgenic B. rapa cultivars with enriched carotenoid levels in the future. PMID- 26138919 TI - Analysis of traction-free assumption in high-resolution EBSD measurements. AB - The effects of using a traction-free (plane-stress) assumption to obtain the full distortion tensor from high-resolution EBSD measurements are analyzed. Equations are derived which bound the traction-free error arising from angular misorientation of the sample surface; the error in recovered distortion is shown to be quadratic with respect to that misorientation, and the maximum 'safe' angular misorientation is shown to be 2.7 degrees. The effects of localized stress fields on the traction-free assumption are then examined by a numerical case study, which uses the Boussinesq formalism to model stress fields near a free surface. Except in cases where localized stress field sources occur very close to sample points, the traction-free assumption appears to be admirably robust. PMID- 26138920 TI - A prepartum diet supplemented with oilseeds high in oleic or linoleic acid reduced GnRH-induced LH release in dairy cows during second week postpartum. AB - BACKGROUND: The objective was to determine the effect of prepartum diets supplemented with rolled canola seed (high in oleic acid) or sunflower seed (high in linoleic acid) on luteinizing hormone (LH) pulsatility and gonadotropin releasing hormone (GnRH)-induced LH release during early postpartum. METHODS: Thirty-one pregnant Holstein cows, blocked by body condition score, parity and expected calving date, were assigned to 1 of 3 prepartum diets supplemented with 8 % rolled canola or sunflower seed, or no oilseed (control) during the last 35 d of gestation. Blood samples were collected at Weeks (wk)-3, 0, +1 and +2, relative to calving, to determine non-esterified fatty acids (NEFA), Beta-hydroxy butyric acid (BHBA) and glucose. Additional blood samples were collected during wk1 (n = 5 per treatment) or wk2 (n = 5 or 6 per treatment), for 6 h, to measure LH pulsatility; thereafter, 100 mcg GnRH was administrated i.m., and blood was sampled for 4 h more, to measure GnRH-induced LH release. RESULTS: Dietary treatment did not affect prepartum energy balance, but cows fed the control diet were in a deeper state of negative energy balance during wk2, than those fed canola (P = 0.03) or sunflower (P = 0.01). Prepartum diets did not influence the mean plasma concentration of BHBA and glucose. However, NEFA concentration during wk2 was greater in control cows than those fed sunflower (P = 0.03) or canola (P = 0.07). Prepartum diets did not affect LH pulsatility (i.e. mean, minimum, maximum concentration, pulse frequency, and amplitude during wk1 and 2). GnRH induced LH release did not differ among dietary treatments during wk1 but the mean GnRH-induced LH release during wk2 was either greater (P = 0.02) and tended to be greater (P = 0.09) in control cows than in those fed canola and sunflower, respectively. CONCLUSIONS: Prepartum diets did not affect LH pulsatility and GnRH induced LH release during the first week postpartum, but cows fed a diet supplemented with oilseeds high in oleic or linoleic acid released less LH than control cows, in response to an exogenous GnRH challenge during the second week postpartum. PMID- 26138921 TI - Integrative network analysis for survival-associated gene-gene interactions across multiple genomic profiles in ovarian cancer. AB - BACKGROUND: Recent advances in high-throughput technology and the emergence of large-scale genomic datasets have enabled detection of genomic features that affect clinical outcomes. Although many previous computational studies have analysed the effect of each single gene or the additive effects of multiple genes on the clinical outcome, less attention has been devoted to the identification of gene-gene interactions of general type that are associated with the clinical outcome. Moreover, the integration of information from multiple molecular profiles adds another challenge to this problem. Recently, network-based approaches have gained huge popularity. However, previous network construction methods have been more concerned with the relationship between features only, rather than the effect of feature interactions on clinical outcome. METHODS: We propose a mutual information-based integrative network analysis framework (MINA) that identifies gene pairs associated with clinical outcome and systematically analyses the resulting networks over multiple genomic profiles. We implement an efficient non-parametric testing scheme that ensures the significance of detected gene interactions. We develop a tool named MINA that automates the proposed analysis scheme of identifying outcome-associated gene interactions and generating various networks from those interacting pairs for downstream analysis. RESULTS: We demonstrate the proposed framework using real data from ovarian cancer patients in The Cancer Genome Atlas (TCGA). Statistically significant gene pairs associated with survival were identified from multiple genomic profiles, which include many individual genes that have weak or no effect on survival. Moreover, we also show that integrated networks, constructed by merging networks from multiple genomic profiles, demonstrate better topological properties and biological significance than individual networks. CONCLUSIONS: We have developed a simple but powerful analysis tool that is able to detect gene-gene interactions associated with clinical outcome on multiple genomic profiles. By being network based, our approach provides a better insight into the underlying gene-gene interaction mechanisms that affect the clinical outcome of cancer patients. PMID- 26138922 TI - Sexual dimorphisms in leukocyte trafficking in a mouse peritonitis model. AB - Sexual dimorphisms exist in the incidence and severity of many diseases, with females demonstrating relative protection from inflammatory conditions. The extent and mechanisms by which excessive leukocyte recruitment underlies these differences are not well established, and better understanding is essential for the development of targeted therapies. Here, we set out to compare the male and female inflammatory response in a murine zymosan-induced peritonitis model and to understand how leukocyte subsets are mobilized from storage pools in both sexes. This work shows that female C57BL/6 mice recruit fewer classical monocytes and neutrophils during zymosan-induced peritonitis. In addition, sex differences were evident in the circulation, as female mice showed reduced neutrophilia and monocytosis vs. male counterparts, despite having similar mobilization from BM stores. Importantly, we show that storage and trafficking of splenic leukocytes during acute inflammation are distinct between the sexes. Male mice have greater splenic stores of neutrophils and classical and nonclassical monocytes, despite similar spleen sizes, signifying another source of potential pathogenic leukocytes. This work demonstrates that males and females have distinct leukocyte trafficking profiles in acute inflammation and suggests that the spleen, not the BM, plays a role in determining sex differences in the available pool of immune cells. Such dimorphisms demonstrate the importance of considering gender in assay development, drug design, and clinical trials. PMID- 26138924 TI - Nasal obstruction and male gender contribute to the persistence of mouth opening during sleep in CPAP-treated obstructive sleep apnoea. AB - BACKGROUND AND OBJECTIVE: During continuous positive airway pressure (CPAP) treatment, some patients with obstructive sleep apnoea syndrome (OSAS) require an oronasal mask (ONM) to prevent excessive mouth leakage. Factors contributing to sleep-related mouth opening under CPAP treatment remain known. We compared mouth opening during sleep in patients treated with CPAP by nasal mask (NM) versus ONM. METHODS: Cross-sectional prospective study: patients treated with CPAP for at least 4 months underwent a sleep recording using a type 4 monitoring device (Brizzy-Nomics) that records mouth opening via a magnetometric distance meter. Clinical assessment included anthropometry, smoking status and the Mallampati score. Nasal obstruction was assessed by the Nasal Obstruction Symptom Evaluation questionnaire. RESULTS: Thirty-eight patients were included, 34 analysed (22 men; age = 57.4 (53; 62) years; body mass index = 32.6 (29.1; 35.2) kg/m(2) ; median (25th; 75th)). Twenty-seven patients were treated with NM and seven with ONM. Patients with ONM were more often active smokers and trended to have greater nasal obstruction and lower forced expiratory volume in 1 s. They also exhibited a greater mouth opening during sleep (median (25th;75th) = 13.0 (11.0; 15.0) vs 6.0 (5.0; 10.0) mm, P < 0.001) and a higher oxygen desaturation index (9.5 (6.2; 15.5) vs 2.9 (1.0; 6.1) events/h, P = 0.009). In multivariate analysis, male gender and nasal obstruction were independently associated with mouth opening under ONM CPAP treatment. CONCLUSIONS: After several months of CPAP treatment, some patients using ONM persist in keeping their mouths open at night. Nasal obstruction and male gender contribute to this phenomenon. PMID- 26138923 TI - Delayed help seeking behavior in dementia care: preliminary findings from the Clinical Pathway for Alzheimer's Disease in China (CPAD) study. AB - BACKGROUND: The prevalence and factors associated with delays in help seeking for people with dementia in China are unknown. METHODS: Within 1,010 consecutively registered participants in the Clinical Pathway for Alzheimer's Disease in China (CPAD) study (NCT01779310), 576 persons with dementia (PWDs) and their informants reported the estimated time from symptom onset to first medical visit seeking diagnosis. Univariate analysis of general linear model was used to examine the potential factors associated with the delayed diagnosis seeking. RESULTS: The median duration from the first noticeable symptom to the first visit seeking diagnosis or treatment was 1.77 years. Individuals with a positive family history of dementia had longer duration (p = 0.05). Compared with other types of dementia, people with vascular dementia (VaD) were referred for diagnosis earliest, and the sequence for such delays was: VaD < Alzheimer's disease (AD) < frontotemporal dementia (FTD) (p < 0.001). Subtypes of dementia (p < 0.001), family history (p = 0.01), and education level (p = 0.03) were associated with the increased delay in help seeking. CONCLUSIONS: In China, seeking diagnosis for PWDs is delayed for approximately 2 years, even in well-established memory clinics. Clinical features, family history, and less education may impede help seeking in dementia care. PMID- 26138925 TI - Healthy lifestyle interventions to combat noncommunicable disease-a novel nonhierarchical connectivity model for key stakeholders: a policy statement from the American Heart Association, European Society of Cardiology, European Association for Cardiovascular Prevention and Rehabilitation, and American College of Preventive Medicine. AB - Noncommunicable diseases (NCDs) have become the primary health concern for most countries around the world. Currently, more than 36 million people worldwide die from NCDs each year, accounting for 63% of annual global deaths; most are preventable. The global financial burden of NCDs is staggering, with an estimated 2010 global cost of $6.3 trillion (US dollars) that is projected to increase to $13 trillion by 2030. A number of NCDs share one or more common predisposing risk factors, all related to lifestyle to some degree: (1) cigarette smoking, (2) hypertension, (3) hyperglycemia, (4) dyslipidemia, (5) obesity, (6) physical inactivity, and (7) poor nutrition. In large part, prevention, control, or even reversal of the aforementioned modifiable risk factors are realized through leading a healthy lifestyle (HL). The challenge is how to initiate the global change, not toward increasing documentation of the scope of the problem but toward true action-creating, implementing, and sustaining HL initiatives that will result in positive, measurable changes in the previously defined poor health metrics. To achieve this task, a paradigm shift in how we approach NCD prevention and treatment is required. The goal of this American Heart Association/European Society of Cardiology/European Association for Cardiovascular Prevention and Rehabilitation/American College of Preventive Medicine policy statement is to define key stakeholders and highlight their connectivity with respect to HL initiatives. This policy encourages integrated action by all stakeholders to create the needed paradigm shift and achieve broad adoption of HL behaviors on a global scale. PMID- 26138926 TI - Curvature Radius Measurements From the Ulnar Trochlear Notch in Large Dogs. AB - Assessing the ulnar trochlear notch (UTN) radiographic anatomy has been considered important, but difficult, in the diagnosis of elbow dysplasia. The purpose of this study was to evaluate UTN curvature of natural elbows in radiographs, using a methodology applied to disarticulated joints. The methodology was implemented and validated using dedicated software created by the authors. Mediolateral extended (MLE) and mediolateral flexed (MLF) elbow views were used from 20 joints from canine cadavers that were over 20 kg. After arranging the bones to avoid radiographic overlapping of the bones, an additional mediolateral radioulnar (MLRU) view was made. Curvature radius measurements from the central ridge of the UTN of each elbow were acquired in the MLRU view, using the software. The measurements were repeated in a second session, to determine repeatability. Then similar UTN measurements were taken from the MLE and MLF views, to determine reproducibility. Intraclass correlation coefficient (ICC) for repeatability and reproducibility of measurements were above 0.98 (95% confidence interval limits >0.75). The 95% limits of agreement (LA) for repeatability were 2.98 to 3.19 mm. The 95% LA for reproducibility between MLRU and MLE views were 4.32 to 3.75 mm. The 95% LA for reproducibility between MLRU and MLF views were 5.02 to 4.07 mm. The methodology and software are determined to be both precise and suitable to evaluate the UTN in MLE and MLF elbow views of large breed dogs, for anatomical and clinical purposes. In the future it would be useful to characterize normal and dysplastic UTN of different dog breeds. PMID- 26138927 TI - The effect of silencing arginine kinase by RNAi on the larval development of Helicoverpa armigera. AB - Arginine kinase (AK) is an important regulation factor of energy metabolism in invertebrate. An arginine kinase gene, named HaAK, was identified to be differentially expressed between Cry1Ac-susceptible (96S) and Cry1Ac-resistant (Bt-R) Helicoverpa armigera larvae using cDNA-amplification fragment length polymorphism analysis. The full-length open reading frame sequence of HaAK gene with 1068 bp was isolated from H. armigera. Quantitative reverse transcription polymerase chain reaction assay revealed that HaAK gene is specifically expressed in multiple tissues and at larval developmental stages. The peak expression level of HaAK was detected in the midgut of the fifth-instar larvae. Moreover, the expression of HaAK was obviously down-regulated in Bt-R larvae. We further constructed a dsRNA vector directly targeting HaAK and employed RNAi technology to control the larvae. The feeding bioassays showed that minute quantities of dsRNA could greatly increase the larval mortality and delay the larval pupation. Silencing of HaAK significantly retarded the larval development, indicating that HaAK is a potential target for RNA interference-based pest management. PMID- 26138928 TI - Artifacts in single-molecule localization microscopy. AB - Single-molecule localization microscopy provides subdiffraction resolution images with virtually molecular resolution. Through the availability of commercial instruments and open-source reconstruction software, achieving super resolution is now public domain. However, despite its conceptual simplicity, localization microscopy remains prone to user errors. Using direct stochastic optical reconstruction microscopy, we investigate the impact of irradiation intensity, label density and photoswitching behavior on the distribution of membrane proteins in reconstructed super-resolution images. We demonstrate that high emitter densities in combination with inappropriate photoswitching rates give rise to the appearance of artificial membrane clusters. Especially, two dimensional imaging of intrinsically three-dimensional membrane structures like microvilli, filopodia, overlapping membranes and vesicles with high local emitter densities is prone to generate artifacts. To judge the quality and reliability of super-resolution images, the single-molecule movies recorded to reconstruct the images have to be carefully investigated especially when investigating membrane organization and cluster analysis. PMID- 26138929 TI - Visualizing posttranslational and epigenetic modifications of endogenous proteins in vivo. AB - Protein localization and dynamics can now be visualized in living cells using the fluorescent protein fusion technique, but it is still difficult to selectively detect molecules with a specific function. As a posttranslational protein modification is often associated with a specific function, marking specifically modified protein molecules in living cells is a way to track an important fraction of protein. In the nucleus, histones are subjected to a variety of modifications such as acetylation and methylation that are associated with epigenetic gene regulation. RNA polymerase II, an enzyme that transcribes genes, is also differentially phosphorylated during the initiation and elongation of transcription. To understand the mechanism of gene regulation in vivo, we have developed methods to track histone and RNA polymerase II modifications using probes derived from modification-specific monoclonal antibodies. In Fab-based live endogenous modification labeling (FabLEM), fluorescently labeled antigen binding fragments (Fabs) are loaded into cells. Fabs bind to target modifications in the nucleus with a binding time of a second to tens of seconds, and so the modification can be tracked without disturbing cell function. For tracking over longer periods of time or in living animals, we have also developed a genetically encoded system to express a modification-specific intracellular antibody (mintbody). Transgenic fruit fly and zebrafish that express histone H3 Lys9 acetylation-specific mintbody developed normally and remain fertile, suggesting that visualizing histone modifications in any tissue in live animals has become possible. These live cell modification tracking techniques will facilitate future studies on epigenetic regulation related to development, differentiation, and disease. Moreover, these techniques can be applied to any other protein modification, opening up new avenues in broad areas in biology and medicine. PMID- 26138930 TI - Fine-needle-aspiration cytology of a proximal type epithelioid sarcoma: A case report. AB - Epithelioid sarcoma is a rare mesenchymal neoplasm, with an as yet unidentified cell of origin. Two subtypes of epithelioid sarcoma, distal/classic and proximal/large cell type, are recognized in the literature; with the proximal type having a lower incidence amongst the two. Here, we present a case of proximal-type epithelioid sarcoma in a previously healthy young man. Fine-needle aspiration of a large axillary mass was performed for diagnosis. The cytologic findings included a dispersed population of large epithelioid to polyhedral cells with abundant cytoplasm. Immunohistochemical staining showed coexpression of keratin and vimentin, as well as loss of INI1 staining, consistent with an epithelioid sarcoma, proximal subtype. PMID- 26138931 TI - Tetrapeptide-coumarin conjugate 3D networks based on hydrogen-bonded charge transfer complexes: gel formation and dye release. AB - Oligopeptide-based derivatives are important synthons for bio-based functional materials. In this article, a Gly-(L-Val)-Gly-(L-Val)-coumarin (GVGV-Cou) conjugate was synthesized, which forms 3D networks in ethanol. The gel nanostructures were characterized by UV-vis spectroscopy, FT-IR spectroscopy, X ray diffraction (XRD), SEM and TEM. It is suggested that the formation of charge transfer (CT) complexes between the coumarin moieties is the main driving force for the gel formation. The capability of the gel to encapsulate and release dyes was explored. Both Congo Red (CR) and Methylene Blue (MB) can be trapped in the CT gel matrix and released over time. The present gel might be used as a functional soft material for guest encapsulation and release. PMID- 26138933 TI - Erratum. PMID- 26138937 TI - Cuba is first country to eliminate mother to child HIV transmission. PMID- 26138938 TI - The modulated structure and frequency upconversion properties of CaLa2(MoO4)4:Ho(3+)/Yb(3+) phosphors prepared by microwave synthesis. AB - CaLa2-x(MoO4)4:Ho(3+)/Yb(3+) phosphors with the doping concentrations of Ho(3+) and Yb(3+) (x = Ho(3+) + Yb(3+), Ho(3+) = 0.05; Yb(3+) = 0.35, 0.40, 0.45 and 0.50) have been successfully synthesized by the microwave sol-gel method. The modulated and averaged crystal structures of CaLa2-x(MoO4)4:Ho(3+)/Yb(3+) molybdates have been found by the Rietveld method, and the upconversion photoluminescence properties have been investigated. The synthesized particles, being formed after the heat-treatment at 900 degrees C for 16 h, showed a highly crystallized state. Under the excitation at 980 nm, CaLa2-x(MoO4)4:Ho(3+)/Yb(3+) particles exhibited strong 545 and 655 nm emission bands in the green and red regions. When the Yb(3+) : Ho(3+) ratios are 9 : 1 and 10 : 1, the UC intensity of CaLa1.5(MoO4)4:Yb0.45/Ho0.05 and CaLa1.45(MoO4)4:Yb0.50/Ho0.05 particles is the highest for different bands. The CIE coordinates calculated for CaLa2 x(MoO4)4:Ho(3+)/Yb(3+) phosphors are related to the yellow color field. The Raman spectrum of undoped CaLa2(MoO4)4 has revealed about 13 narrow lines. The strongest band observed at 906 cm(-1) was assigned to the nu1 symmetric stretching vibration of MoO4 tetrahedra. The spectra of the samples doped with Ho and Yb, as obtained under the 514.5 nm excitation, were dominated by Ho(3+) luminescence over the wavenumber range of >700 cm(-1) preventing the recording of the Raman spectra. PMID- 26138936 TI - Transciptomic and histological analysis of hepatopancreas, muscle and gill tissues of oriental river prawn (Macrobrachium nipponense) in response to chronic hypoxia. AB - BACKGROUND: Oriental river prawn, Macrobrachium nipponense, is a commercially important species found in brackish and fresh waters throughout China. Chronic hypoxia is a major physiological challenge for prawns in culture, and the hepatopancreas, muscle and gill tissues play important roles in adaptive processes. However, the effects of dissolved oxygen availability on gene expression and physiological functions of those tissues of prawns are unknown. Adaptation to hypoxia is a complex process, to help us understand stress-sensing mechanism and ultimately permit selection for hypoxia- tolerant prawns, we performed transcriptomic analysis of juvenile M. nipponense hepatopancreas, gill and muscle tissues by RNA-Seq. RESULTS: Approximately 46,472,741; 52,773,612 and 58,195,908 raw sequence reads were generated from hepatopancreas, muscle and gill tissues, respectively. A total of 62,722 unigenes were generated, of the assembled unigenes, we identified 8,892 genes that were significantly up regulated, while 5,760 genes were significantly down-regulated in response to chronic hypoxia. Genes from well known functional categories and signaling pathways associated with stress responses and adaptation to extreme environments were significantly enriched, including genes in the functional categories "response to stimulus", "transferase activity" and "oxidoreductase activity", and the signaling pathways "oxidative phosphorylation", "glycolysis/gluconeogenesis" and "MAPK signaling". The expression patterns of 18 DEGs involved in hypoxic regulation of M. nipponense were validated by quantitative real-time reverse transcriptase polymerase chain reactions (qRT-PCR; average correlation coefficient = 0.94). In addition, the hepatopancreas and gills exhibited histological differences between hypoxia and normoxia groups. These structural alterations could affect the vital physiological functions of prawns in response to chronic hypoxia, which could adversely affect growth and survival of M. nipponense. CONCLUSIONS: Gene expression changes in tissues from the oriental river prawn provide a preliminary basis to better understand the molecular responses of M. nipponense to chronic hypoxia. The differentially expressed genes (DEGs) identified in M. nipponense under hypoxia stress may be important for future genetic improvement of cultivated prawns or other crustaceans through transgenic approaches aimed at increasing hypoxia tolerance. PMID- 26138939 TI - Synergistic Catalysis: Metal/Proton-Catalyzed Cyclization of Alkynones Toward Bicyclo[3.n.1]alkanones. AB - A highly efficient and practical synergistically metal/proton-catalyzed Conia-ene reaction for the synthesis of bicyclo[3.n.1]alkanones has been developed. This synergistic catalysis was successfully utilized in modifying natural compounds such as methyl dihydrojasmonate, alpha,beta-thujone, and 5alpha-cholestan-3-one. Furthermore, the bridged carbonyl group of bicyclo[3.2.1]alkanones could be easily attacked by nucleophiles to give the ring-opened cycloheptenone products or bicyclo[4.2.1]amide in excellent yields. These reactions provide rapid access to a diverse range of cyclic structures from simple starting materials or naturally occurring compounds. PMID- 26138941 TI - It's not all traction: the pseudo 'fringe sign' in frontal fibrosing alopecia. PMID- 26138940 TI - Barriers for Deriving Transgene-Free Pig iPS Cells with Episomal Vectors. AB - To date no authentic embryonic stem cell (ESC) line or germline-competent-induced pluripotent stem cell (iPSC) line has been established for large animals. Despite this fact, there is an impression in the field that large animal ESCs or iPSCs are as good as mouse counterparts. Clarification of this issue is important for a healthy advancement of the stem cell field. Elucidation of the causes of this failure in obtaining high quality iPSCs/ESCs may offer essential clues for eventual establishment of authentic ESCs for large animals including humans. To this end, we first generated porcine iPSCs using nonintegrating replicating episomal plasmids. Although these porcine iPSCs met most pluripotency criteria, they could neither generate cloned piglets through nuclear transfer, nor contribute to later stage chimeras through morula injections or aggregations. We found that the reprogramming genes in iPSCs could not be removed even under negative selection, indicating they are required to maintain self-renewal. The persistent expression of these genes in porcine iPSCs in turn caused differentiation defects in vivo. Therefore, incomplete reprogramming manifested by a reliance on sustained expression of exogenous-reprogramming factors appears to be the main reason for the inability of porcine iPSCs to form iPSC-derived piglets. PMID- 26138943 TI - Comment: Prescription opioids-Misused or misunderstood? PMID- 26138942 TI - When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. AB - OBJECTIVE: To determine ways to improve diagnostic accuracy of multiple system atrophy (MSA), we assessed the diagnostic process in patients who came to autopsy with antemortem diagnosis of MSA by comparing clinical and pathologic features between those who proved to have MSA and those who did not. We focus on likely explanations for misdiagnosis. METHODS: This is a retrospective review of 134 consecutive patients with an antemortem clinical diagnosis of MSA who came to autopsy with neuropathologic evaluation of the brain. Of the 134 patients, 125 had adequate medical records for review. Clinical and pathologic features were compared between patients with autopsy-confirmed MSA and those with other pathologic diagnoses, including dementia with Lewy bodies (DLB), Parkinson disease (PD), and progressive supranuclear palsy (PSP). RESULTS: Of the 134 patients with clinically diagnosed MSA, 83 (62%) had the correct diagnosis at autopsy. Pathologically confirmed DLB was the most common misdiagnosis, followed by PSP and PD. Despite meeting pathologic criteria for intermediate to high likelihood of DLB, several patients with DLB did not have dementia and none had significant Alzheimer-type pathology. Autonomic failure was the leading cause of misdiagnosis in DLB and PD, and cerebellar ataxia was the leading cause of misdiagnosis in PSP. CONCLUSIONS: The diagnostic accuracy for MSA was suboptimal in this autopsy study. Pathologically confirmed DLB, PD, and PSP were the most common diseases to masquerade as MSA. This has significant implications not only for patient care, but also for research studies in MSA cases that do not have pathologic confirmation. PMID- 26138944 TI - Respiratory dyskinesia in a patient with Parkinson disease successfully treated with STN DBS. PMID- 26138945 TI - The end of life with PD can be well-lived: the neurologist's role. PMID- 26138946 TI - Opioids for chronic noncancer pain: To prescribe or not to prescribe-What is the question? AB - The recent American Academy of Neurology position paper by Franklin, "Opioids for chronic noncancer pain," suggests that the benefits of opioid treatment are very likely to be substantially outweighed by the risks and recommends avoidance of doses above 80-120 mg/day morphine equivalent. However, close reading of the primary literature supports a different conclusion: opioids have been shown in randomized controlled trials (RCTs) to be highly effective in the treatment of chronic nonmalignant pain; long-term follow-up studies have shown that this effectiveness can be maintained; and effectiveness has been limited in many clinical trials by failure to take into account high variability in dose requirements, failure to adequately treat depression, and use of suboptimal outcome measures. Frequency of side effects in many RCTs has been inflated by overly rapid dose titration and failure to appreciate the high interindividual variability in side effect profiles. The recent marked increase in incidence of opioid overdose is of grave concern, but there is good reason to believe that it has been somewhat exaggerated. Potential causes of overdose include inadequately treated depression; inadequately treated pain, particularly when compounded by hopelessness; inadvertent overdose; concurrent use of alcohol; and insufficient practitioner expertise. Effective treatment of pain can enable large numbers of patients to lead productive lives and improve quality of life. Effective alleviation of suffering associated with pain falls squarely within the physician's professional obligation. Existing scientific studies provide the basis for many improvements in pain management that can increase effectiveness and reduce risk. Many potentially useful areas of further research can be identified. PMID- 26138947 TI - Nursing home and end-of-life care in Parkinson disease. AB - OBJECTIVE: To examine long-term care facility (LTCF or nursing home) use and end of-life care for individuals with Parkinson disease (PD). METHODS: In this nationwide retrospective cohort study, we compared LTCF and hospice utilization among Medicare beneficiaries diagnosed with PD by demographic, clinical, and physician characteristics. We also examined the impact of outpatient neurologist care for institutionalized patients with PD on end-of-life care. RESULTS: We identified 469,055 individuals with PD who received Medicare benefits in 2002. Nearly 25% (more than 100,000 in total) resided in an LTCF. Women with PD had greater odds of nursing facility residence (adjusted odds ratio [AOR] 1.34, 95% confidence interval [CI] 1.30-1.38) compared with men. Black individuals with PD were 34% more likely than white individuals to reside in an LTCF (AOR 1.34, 95% CI 1.30-1.38), contrary to the race patterns typically observed for LTCF use. Hip fracture (AOR 2.10, 95% CI 2.04-2.15) and dementia (AOR 4.06, 95% CI 4.00-4.12) were the strongest clinical predictors of LTCF placement. Only 33% (n = 38,334) of nursing home residents with PD had outpatient neurologist care. Eighty-four percent (n = 80,877) of LTCF residents with PD died by December 31, 2005. Hospice utilization varied little by race and sex. LTCF residents who had outpatient neurologist care were twice as likely to utilize hospice services before death (AOR 2.35, 95% CI 2.24-2.47). CONCLUSIONS AND RELEVANCE: A large proportion of the Medicare PD population resides in an LTCF. There is substantial unmet need for palliative care in the PD population. Increased efforts to provide specialist care to dependent individuals with PD may improve end-of-life care. PMID- 26138948 TI - Facilitating text reading in posterior cortical atrophy. AB - OBJECTIVE: We report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA. METHODS: Reading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2). RESULTS: Mean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6% 270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA. CONCLUSIONS: These findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy. PMID- 26138949 TI - A practical, simple, and useful method of categorizing interictal EEG features in children. AB - We introduce a simple scheme of categorizing interictal EEG in patients with pediatric epilepsy. Five patterns of EEG can be determined by using 2 interictal EEG domains: organization of the background activity and a morphology/topography of epileptiform discharges. These patterns relate to commonly recognized categories of pediatric epilepsy: familial epilepsies, genetic generalized epilepsies, self-limited epilepsies, epilepsies with encephalopathy, and focal structural epilepsies. Each group has distinguishable clinical presentations, inheritance patterns, and outcomes. This categorization may be a useful educational tool; it may also guide decisions about further testing and management. PMID- 26138950 TI - Characteristic features and progression of abnormalities on MRI for CARASIL. AB - OBJECTIVES: The objective of this study was to clarify the characteristic brain MRI findings for genetically diagnosed CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). METHODS: Seven patients with CARASIL carrying HTRA1 mutations (representing 6 Japanese families) were included in this study. Eighteen brain MRIs were reviewed and evaluated with a new rating scale based on scoring for abnormal hyperintense lesions and atrophy. RESULTS: At the last follow-up MRI, all patients had hyperintense lesions on T2-weighted images of the frontal white matter, anterior temporal lobe, external capsules, and thalami. Patients with longer time from the onset of cognitive impairment had higher MRI severity score. The atrophy advanced, followed by white matter lesion progression. During the early stage, hyperintense lesions were observed in the frontal white matter, external capsule, and pons. During the late stage, the arc-shaped hyperintense lesion from the pons to the middle cerebellar peduncles, which we designated the "arc sign," became evident. The arc sign was a characteristic finding for CARASIL in the advanced stage. CONCLUSIONS: These characteristic MRI findings for CARASIL are useful for selecting patients for genetic testing. The rating scale correlates well with disease duration and might be useful for assessing disease progression. PMID- 26138951 TI - New Australian lesbian, gay, bisexual and transgender research--and the need for more. PMID- 26138952 TI - The beyond-two-degree inferno. PMID- 26138955 TI - BIOMEDICAL RESEARCH. Spending bills put NIH on track for biggest raise in 12 years. PMID- 26138954 TI - ARCHAEOLOGY. Development threatens home of early humans. PMID- 26138957 TI - ASTRONOMY. Small scopes log an ever-changing sky. PMID- 26138956 TI - Q&A. Geologist reflects on life behind bars in China. PMID- 26138958 TI - PUBLIC ATTITUDES. Politics doesn't always rule. PMID- 26138959 TI - INFLUENZA. Narcolepsy link to pandemic flu vaccine becomes clearer. PMID- 26138960 TI - The liver's weighty problem. PMID- 26138961 TI - Of mice and men. PMID- 26138963 TI - BIOCHEMISTRY. The flowering of a new scent pathway in rose. PMID- 26138964 TI - BIOMECHANICS. When it's hip to be square. PMID- 26138965 TI - BRAIN EVOLUTION. Knowing when to fold them. PMID- 26138966 TI - GEOMORPHOLOGY. Landscapes in the lab. PMID- 26138967 TI - ENZYMOLOGY. It costs more than a nickel. PMID- 26138968 TI - HEALTH CARE POLICY. Ten things we have to do to achieve precision medicine. PMID- 26138969 TI - PHYSICS. Observation of phononic helical edge states in a mechanical topological insulator. AB - A topological insulator, as originally proposed for electrons governed by quantum mechanics, is characterized by a dichotomy between the interior and the edge of a finite system: The bulk has an energy gap, and the edges sustain excitations traversing this gap. However, it has remained an open question whether the same physics can be observed for systems obeying Newton's equations of motion. We conducted experiments to characterize the collective behavior of mechanical oscillators exhibiting the phenomenology of the quantum spin Hall effect. The phononic edge modes are shown to be helical, and we demonstrate their topological protection via the stability of the edge states against imperfections. Our results may enable the design of topological acoustic metamaterials that can capitalize on the stability of the surface phonons as reliable wave guides. PMID- 26138970 TI - GEOMORPHOLOGY. Experimental evidence for hillslope control of landscape scale. AB - Landscape evolution theory suggests that climate sets the scale of landscape dissection by modulating the competition between diffusive processes that sculpt convex hillslopes and advective processes that carve concave valleys. However, the link between the relative dominance of hillslope and valley transport processes and landscape scale is difficult to demonstrate in natural landscapes due to the episodic nature of erosion. Here, we report results from laboratory experiments combining diffusive and advective processes in an eroding landscape. We demonstrate that rainsplash-driven disturbances in our experiments are a robust proxy for hillslope transport, such that increasing hillslope transport efficiency decreases drainage density. Our experimental results demonstrate how the coupling of climate-driven hillslope- and valley-forming processes, such as bioturbation and runoff, dictates the scale of eroding landscapes. PMID- 26138971 TI - POROUS MATERIALS. Transient laser heating induced hierarchical porous structures from block copolymer-directed self-assembly. AB - Development of rapid processes combining hierarchical self-assembly with mesoscopic shape control has remained a challenge. This is particularly true for high-surface-area porous materials essential for applications including separation and detection, catalysis, and energy conversion and storage. We introduce a simple and rapid laser writing method compatible with semiconductor processing technology to control three-dimensionally continuous hierarchically porous polymer network structures and shapes. Combining self-assembly of mixtures of block copolymers and resols with spatially localized transient laser heating enables pore size and pore size distribution control in all-organic and highly conducting inorganic carbon films with variable thickness. The method provides all-laser-controlled pathways to complex high-surface-area structures, including fabrication of microfluidic devices with high-surface-area channels and complex porous crystalline semiconductor nanostructures. PMID- 26138972 TI - SULFUR CHEMISTRY. Gas phase observation and microwave spectroscopic characterization of formic sulfuric anhydride. AB - We report the observation of a covalently bound species, formic sulfuric anhydride (FSA), that is produced from formic acid and sulfur trioxide under supersonic jet conditions. FSA has been structurally characterized by means of microwave spectroscopy and further investigated by using density functional theory and ab initio calculations. Theory indicates that a pi2 + pi2 + sigma2 cycloaddition reaction between SO3 and HCOOH is a plausible pathway to FSA formation and that such a mechanism would be effectively barrierless. We speculate on the possible role that FSA may play in the Earth's atmosphere. PMID- 26138973 TI - ORGANIC CHEMISTRY. Catalytic asymmetric hydroamination of unactivated internal olefins to aliphatic amines. AB - Catalytic assembly of enantiopure aliphatic amines from abundant and readily available precursors has long been recognized as a paramount challenge in synthetic chemistry. Here, we describe a mild and general copper-catalyzed hydroamination that effectively converts unactivated internal olefins-an important yet unexploited class of abundant feedstock chemicals-into highly enantioenriched alpha-branched amines (>=96% enantiomeric excess) featuring two minimally differentiated aliphatic substituents. This method provides a powerful means to access a broad range of advanced, highly functionalized enantioenriched amines of interest in pharmaceutical research and other areas. PMID- 26138974 TI - METALLOPROTEINS. A tethered niacin-derived pincer complex with a nickel-carbon bond in lactate racemase. AB - Lactic acid racemization is involved in lactate metabolism and cell wall assembly of many microorganisms. Lactate racemase (Lar) requires nickel, but the nickel binding site and the role of three accessory proteins required for its activation remain enigmatic. We combined mass spectrometry and x-ray crystallography to show that Lar from Lactobacillus plantarum possesses an organometallic nickel containing prosthetic group. A nicotinic acid mononucleotide derivative is tethered to Lys(184) and forms a tridentate pincer complex that coordinates nickel through one metal-carbon and two metal-sulfur bonds, with His(200) as another ligand. Although similar complexes have been previously synthesized, there was no prior evidence for the existence of pincer cofactors in enzymes. The wide distribution of the accessory proteins without Lar suggests that it may play a role in other enzymes. PMID- 26138975 TI - PRESYNAPTIC NETWORKS. Single-cell-initiated monosynaptic tracing reveals layer specific cortical network modules. AB - Individual cortical neurons can selectively respond to specific environmental features, such as visual motion or faces. How this relates to the selectivity of the presynaptic network across cortical layers remains unclear. We used single cell-initiated, monosynaptically restricted retrograde transsynaptic tracing with rabies viruses expressing GCaMP6s to image, in vivo, the visual motion-evoked activity of individual layer 2/3 pyramidal neurons and their presynaptic networks across layers in mouse primary visual cortex. Neurons within each layer exhibited similar motion direction preferences, forming layer-specific functional modules. In one-third of the networks, the layer modules were locked to the direction preference of the postsynaptic neuron, whereas for other networks the direction preference varied by layer. Thus, there exist feature-locked and feature-variant cortical networks. PMID- 26138976 TI - BRAIN STRUCTURE. Cortical folding scales universally with surface area and thickness, not number of neurons. AB - Larger brains tend to have more folded cortices, but what makes the cortex fold has remained unknown. We show that the degree of cortical folding scales uniformly across lissencephalic and gyrencephalic species, across individuals, and within individual cortices as a function of the product of cortical surface area and the square root of cortical thickness. This relation is derived from the minimization of the effective free energy associated with cortical shape according to a simple physical model, based on known mechanisms of axonal elongation. This model also explains the scaling of the folding index of crumpled paper balls. We discuss the implications of this finding for the evolutionary and developmental origin of folding, including the newfound continuum between lissencephaly and gyrencephaly, and for pathologies such as human lissencephaly. PMID- 26138977 TI - GREEN CHEMISTRY. Shape-selective zeolite catalysis for bioplastics production. AB - Biodegradable and renewable polymers, such as polylactic acid, are benign alternatives for petrochemical-based plastics. Current production of polylactic acid via its key building block lactide, the cyclic dimer of lactic acid, is inefficient in terms of energy, time, and feedstock use. We present a direct zeolite-based catalytic process, which converts lactic acid into lactide. The shape-selective properties of zeolites are essential to attain record lactide yields, outperforming those of the current multistep process by avoiding both racemization and side-product formation. The highly productive process is strengthened by facile recovery and practical reactivation of the catalyst, which remains structurally fit during at least six consecutive reactions, and by the ease of solvent and side-product recycling. PMID- 26138978 TI - PLANT VOLATILES. Biosynthesis of monoterpene scent compounds in roses. AB - The scent of roses (Rosa x hybrida) is composed of hundreds of volatile molecules. Monoterpenes represent up to 70% percent of the scent content in some cultivars, such as the Papa Meilland rose. Monoterpene biosynthesis in plants relies on plastid-localized terpene synthases. Combining transcriptomic and genetic approaches, we show that the Nudix hydrolase RhNUDX1, localized in the cytoplasm, is part of a pathway for the biosynthesis of free monoterpene alcohols that contribute to fragrance in roses. The RhNUDX1 protein shows geranyl diphosphate diphosphohydrolase activity in vitro and supports geraniol biosynthesis in planta. PMID- 26138979 TI - DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers. AB - There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics. PMID- 26138980 TI - SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding. AB - Selenocysteine (Sec) is translated from the codon UGA, typically a termination signal. Codon duality extends the genetic code; however, the coexistence of two competing UGA-decoding mechanisms immediately compromises proteome fidelity. Selenium availability tunes the reassignment of UGA to Sec. We report a CRL2 ubiquitin ligase-mediated protein quality-control system that specifically eliminates truncated proteins that result from reassignment failures. Exposing the peptide immediately N-terminal to Sec, a CRL2 recognition degron, promotes protein degradation. Sec incorporation destroys the degron, protecting read through proteins from detection by CRL2. Our findings reveal a coupling between directed translation termination and proteolysis-assisted protein quality control, as well as a cellular strategy to cope with fluctuations in organismal selenium intake. PMID- 26138981 TI - Find your most interesting question. PMID- 26138982 TI - OCEANOGRAPHY. Contrasting futures for ocean and society from different anthropogenic CO2 emissions scenarios. AB - The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems-and the goods and services they provide-for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend. A reduced emissions scenario-consistent with the Copenhagen Accord's goal of a global temperature increase of less than 2 degrees C-is much more favorable to the ocean but still substantially alters important marine ecosystems and associated goods and services. The management options to address ocean impacts narrow as the ocean warms and acidifies. Consequently, any new climate regime that fails to minimize ocean impacts would be incomplete and inadequate. PMID- 26138983 TI - BIOMECHANICS. Why the seahorse tail is square. AB - Whereas the predominant shapes of most animal tails are cylindrical, seahorse tails are square prisms. Seahorses use their tails as flexible grasping appendages, in spite of a rigid bony armor that fully encases their bodies. We explore the mechanics of two three-dimensional-printed models that mimic either the natural (square prism) or hypothetical (cylindrical) architecture of a seahorse tail to uncover whether or not the square geometry provides any functional advantages. Our results show that the square prism is more resilient when crushed and provides a mechanism for preserving articulatory organization upon extensive bending and twisting, as compared with its cylindrical counterpart. Thus, the square architecture is better than the circular one in the context of two integrated functions: grasping ability and crushing resistance. PMID- 26138984 TI - Increased spread and replication efficiency of Listeria monocytogenes in organotypic brain-slices is related to multilocus variable number of tandem repeat analysis (MLVA) complex. AB - BACKGROUND: Listeria (L.) monocytogenes causes fatal infections in many species including ruminants and humans. In ruminants, rhombencephalitis is the most prevalent form of listeriosis. Using multilocus variable number tandem repeat analysis (MLVA) we recently showed that L. monocytogenes isolates from ruminant rhombencephalitis cases are distributed over three genetic complexes (designated A, B and C). However, the majority of rhombencephalitis strains and virtually all those isolated from cattle cluster in MLVA complex A, indicating that strains of this complex may have increased neurotropism and neurovirulence. The aim of this study was to investigate whether ruminant rhombencephalitis strains have an increased ability to propagate in the bovine hippocampal brain-slice model and can be discriminated from strains of other sources. For this study, forty-seven strains were selected and assayed on brain-slice cultures, a bovine macrophage cell line (BoMac) and a human colorectal adenocarcinoma cell line (Caco-2). They were isolated from ruminant rhombencephalitis cases (n = 21) and other sources including the environment, food, human neurolisteriosis cases and ruminant/human non-encephalitic infection cases (n = 26). RESULTS: All but one L. monocytogenes strain replicated in brain slices, irrespectively of the source of the isolate or MLVA complex. The replication of strains from MLVA complex A was increased in hippocampal brain-slice cultures compared to complex C. Immunofluorescence revealed that microglia are the main target cells for L. monocytogenes and that strains from MLVA complex A caused larger infection foci than strains from MLVA complex C. Additionally, they caused larger plaques in BoMac cells, but not CaCo 2 cells. CONCLUSIONS: Our brain slice model data shows that all L. monocytogenes strains should be considered potentially neurovirulent. Secondly, encephalitis strains cannot be conclusively discriminated from non-encephalitis strains with the bovine organotypic brain slice model. The data indicates that MLVA complex A strains are particularly adept at establishing encephalitis possibly by virtue of their higher resistance to antibacterial defense mechanisms in microglia cells, the main target of L. monocytogenes. PMID- 26138985 TI - Childhood socioeconomic position and adult leisure-time physical activity: a systematic review. AB - Regular leisure-time physical activity (LTPA) benefits health and is thought to be less prevalent in lower socioeconomic groups. Evidence suggests that childhood socioeconomic circumstances can impact on adult health and behaviour however, it is unclear if this includes an influence on adult LTPA. This review tested the hypothesis that a lower childhood socioeconomic position (SEP) is associated with less frequent LTPA during adulthood. Studies were located through a systematic search of MEDLINE, Embase, PsycINFO, CINAHL and SPORTDiscus and by searching reference lists. Eligible studies were English-language publications testing the association between any indicator of childhood SEP and an LTPA outcome measured during adulthood. Forty-five papers from 36 studies, most of which were European, were included. In most samples, childhood SEP and LTPA were self-reported in midlife. Twenty-two studies found evidence to support the review's hypothesis and thirteen studies found no association. Accounting for own adult SEP partly attenuated associations. There was more evidence of an association in British compared with Scandinavian cohorts and in women compared with men. Results did not vary by childhood SEP indicator or age at assessment of LTPA. This review found evidence of an association between less advantaged childhood SEP and less frequent LTPA during adulthood. Understanding how associations vary by gender and place could provide insights into underlying pathways. PMID- 26138986 TI - Selective Differentiation into Hematopoietic and Cardiac Cells from Pluripotent Stem Cells Based on the Expression of Cell Surface Markers. AB - Flk1-expressing (+) mesodermal cells are useful source for the generation of hematopoietic cells and cardiomyocytes from pluripotent stem cells (PSCs). However, they have been reported as a heterogenous population that includes hematopoietic and cardiac progenitors. Therefore, to provide a method for a highly efficient production of hematopoietic cells and cardiomyocytes, cell surface markers are often used for separating these progenitors in Flk1(+) cells. Our recent study has shown that the expression of coxsackievirus and adenovirus receptor (CAR), a tight junction component molecule, could divide mouse and human PSC- and mouse embryo-derived Flk1(+) cells into Flk1(+)CAR(-) and Flk1(+)CAR(+) cells. Flk1(+)CAR(-) and Flk1(+)CAR(+) cells efficiently differentiated into hematopoietic cells and cardiomyocytes, respectively. These results indicate that CAR is a novel cell surface marker for separating PSC-derived Flk1(+) mesodermal cells into hematopoietic and cardiac progenitors. We herein describe a differentiation method from PSCs into hematopoietic cells and cardiomyocytes based on CAR expression. PMID- 26138987 TI - Nano-MeDIP-seq Methylome Analysis Using Low DNA Concentrations. AB - DNA methylation is an epigenetic mark that is indispensable for mammalian development and occurs at cytosine residues throughout the genome (the "methylome"). Approximately 70 % of all CpG dinucleotides are affected by DNA methylation, which serve to "lock in" chromatin states and thus transcriptional programs. The systemic and pervasive occurrence of DNA methylation throughout the genome defines cellular identity and therefore requires genome-wide assays to fully appreciate and discern differential patterns of methylation that influence aspects of phenotypic plasticity including susceptibility to common complex disease.One method that permits methylome analysis is methylated DNA immunoprecipitation (MeDIP) combined with next-generation sequencing (MeDIP-seq). MeDIP uses an antibody raised against 5-methylcytosine to capture methylated fragments of DNA, which are subsequently sequenced to envisage the methylome landscape. The advantageous cost versus coverage balance of MeDIP-seq has made it the method of choice to replace or complement array-based methods for population epigenetic studies. Here we detail nano-MeDIP-seq, which allows methylome analysis using nanogram quantities of starting material. PMID- 26138988 TI - Bisulfite Conversion of DNA from Tissues, Cell Lines, Buffy Coat, FFPE Tissues, Microdissected Cells, Swabs, Sputum, Aspirates, Lavages, Effusions, Plasma, Serum, and Urine. AB - Locus-specific analyses of DNA methylation patterns usually require a bisulfite conversion of the DNA, where cytosines are deaminated to uracils, while methylated and hydroxymethylated cytosines remain unaffected. The specific discrimination of hydroxymethylation and methylation can be achieved by introducing an oxidation of 5-hydroxymethylcytosines to 5-formylcytosines and subsequent bisulfite-mediated deamination of 5-formylcytosines.DNA methylation analysis of cell-free circulating DNA in liquid biopsies, i.e., blood samples (serum and plasma), urine, aspirates, bronchial lavages, pleural effusions, and ascites, is of great interest in clinical research. However, due to the generally low concentration of circulating cell-free DNA in body fluids, high volumes need to be analyzed. A reduction of this volume, e.g., by means of a polymer-mediated enrichment, is required in order to facilitate the bisulfite conversion. Further, these sample types usually contain a cellular fraction which is of additional interest and requires specific protocols for the sample preparation.Formalin fixed, paraffin-embedded (FFPE) tissue is the most commonly used source for tissue-based clinical research. Due to degradation and covalent modifications of DNA in FFPE tissue samples, optimized protocols for the DNA preparation and bisulfite conversion are required.This chapter describes methods and protocols for the sample preparation and subsequent high-speed bisulfite conversion and DNA clean-up for several types of relevant samples, i.e., serum, plasma, urine, buffy coat, aspirates, sputum, lavages, effusions, ascites, swabs, fresh tissues, cell lines, FFPE tissues, and laser microdissected cells.Additionally, two real-time PCR assays for DNA quantification and quality control are described. The cytosine free fragment (CFF) assay allows for the simultaneous quantification of bisulfite converted and total DNA and thus the determination of bisulfite conversion efficiency. The Mer9 real-time PCR assay amplifies the bisulfite converted sequence of the repetitive element Mer9 and enables the accurate quantification of minute DNA amounts, as present in microdissected cells and body fluids. PMID- 26138989 TI - Clinical and Electrophysiological Markers in Myasthenia Gravis Patients. AB - OBJECTIVE: We investigated the correlation between disease severity and electrophysiological characteristics in 77 Chinese myasthenia gravis (MG) patients. MATERIALS AND METHODS: Disease severity was assessed and compared with repetitive nerve stimulation (RNS) and needle electrode electromyography (NEMG) evaluations. RESULTS: The quantified myasthenia gravis (QMG) and MG-activities of daily living (MG-ADL) scores correlated well with the proximal muscle decremental response rate. NEMG revealed that 22 patients (28.6%) had myopathic changes, but none demonstrated spontaneous potentials. Only motor unit potentials showed short durations and low amplitude changes. Patients with myopathic changes had higher QMG and MG-ADL scores, and their classifications were different from patients with normal NEMG results. CONCLUSIONS: Decreased RNS compound muscle action potential amplitudes correlated with MG severity, and were more pronounced in the proximal than in the distal muscles. Patients with myopathic changes showed more severe disease characteristics. Thus, electrophysiological tests are useful for MG diagnosis and can indicate disease severity. PMID- 26138990 TI - Direct writing of tunable multi-wavelength polymer lasers on a flexible substrate. AB - Tunable multi-wavelength polymer lasers based on two-dimensional distributed feedback structures are fabricated on a transparent flexible substrate using interference ablation. A scalene triangular lattice structure was designed to support stable tri-wavelength lasing emission and was achieved through multiple exposure processes. Three wavelengths were controlled by three periods of the compound cavity. Mode competition among different cavity modes was observed by changing the pump fluence. Both a redshift and blueshift of the laser wavelength could be achieved by bending the soft substrate. These results not only provide insight into the physical mechanisms behind co-cavity polymer lasers but also introduce new laser sources and laser designs for white light lasers. PMID- 26138991 TI - Long-Pulsed Neodymium-Doped Yttrium Aluminum Garnet Laser for Glomuvenous Malformations in Adolescents. AB - Currently there exist few reported cases where lasers are used successfully to treat glomuvenous malformations in adolescents. In the two cases described here, we provide evidence that the long-pulsed neodymium-doped yttrium aluminum garnet laser is an effective and safe alternative treatment for these lesions. Our case series is unique because it focuses on adolescents, the population that most often seeks treatment for this dermatologic condition. PMID- 26138992 TI - Translational Genomics in Low- and Middle-Income Countries: Opportunities and Challenges. AB - Translation of genomic discoveries into patient care is slowly becoming a reality in developed economies around the world. In contrast, low- and middle-income countries (LMIC) have participated minimally in genomic research for several reasons including the lack of coherent national policies, the limited number of well-trained genomic scientists, poor research infrastructure, and local economic and cultural challenges. Recent initiatives such as the Human Heredity and Health in Africa (H3Africa), the Qatar Genome Project, and the Mexico National Institute of Genomic Medicine (INMEGEN) that aim to address these problems through capacity building and empowerment of local researchers have sparked a paradigm shift. In this short communication, we describe experiences of small-scale medical genetics and translational genomic research programs in LMIC. The lessons drawn from these programs drive home the importance of addressing resource, policy, and sociocultural dynamics to realize the promise of precision medicine driven by genomic science globally. By echoing lessons from a bench-to-community translational genomic research, we advocate that large-scale genomic research projects can be successfully linked with health care programs. To harness the benefits of genomics-led health care, LMIC governments should begin to develop national genomics policies that will address human and technology capacity development within the context of their national economic and sociocultural uniqueness. These policies should encourage international collaboration and promote the link between the public health program and genomics researchers. Finally, we highlight the potential catalytic roles of the global community to foster translational genomics in LMIC. PMID- 26138993 TI - Population pharmacokinetic modeling and simulation for assessing renal impairment effect on the pharmacokinetics of mirogabalin. AB - A population pharmacokinetic model was developed to describe plasma concentrations of mirogabalin and lactam metabolite, obtained following a single oral dose of 5 mg mirogabalin to subjects with varying degrees of renal function.A 2-compartment model was used for both mirogabalin and lactam metabolite. Body weight was a significant covariate on volume of distribution of mirogabalin and lactam metabolite, whereas creatinine clearance significantly affected both renal and nonrenal clearance of mirogabalin. The total clearance of mirogabalin was decreased by 25%, 54%, and 76% in subjects with mild, moderate, and severe renal impairment, respectively, relative to normal controls. Simulation results showed that in comparison with the normal renal function group receiving mirogabalin 15 mg once or twice daily, dose reduction by 50% or 75% in subjects with moderate or severe renal impairment would produce similar AUCss values, but 37%-43% or 28%-32% lower Cmax,ss of mirogabalin. Predicted mirogabalin AUCss was 26% higher, whereas Cmax,ss was similar in subjects with mild renal impairment compared with those having normal renal function taking the same dose. Results support a dose reduction by 50% or 75% in subjects with moderate or severe renal impairment. No dose adjustment seemed necessary for subjects with mild renal impairment. PMID- 26138994 TI - Association between Obesity and Chronic Laryngitis in Women--Data from the Korea National Health and Nutrition Examination Survey. AB - BACKGROUND: This study aimed to investigate the relationship between obesity and chronic laryngitis in South Korea using data from the Korea National Health and Nutrition Examination Surveys (KNHANES) collected during 2008-2010. METHODS: KNHANES was a cross-sectional survey of the civilian, non-institutionalized population of South Korea (n = 13,819). Obesity status was measured by using BMI and waist circumference. RESULTS: Among the population over 19 years of age, the prevalence of chronic laryngitis was 4.0 +/- 0.4%. Chronic laryngitis was significantly associated with age, BMI, waist circumference, fat proportion, both systolic and diastolic blood pressure, fasting blood sugar, triglycerides, and high-density lipoprotein cholesterol in women. Old age and current smoking were significantly associated with chronic laryngitis in men. Obese women were at a higher risk for chronic laryngitis than women without obesity (odds ratio (OR) 2.022, 95% confidence interval (95% CI) 1.412-2.895) after further adjustment for confounders. Women with abdominal obesity were also at higher risk for chronic laryngitis (OR 1.475, 95% CI 1.024-2.126). CONCLUSION: Obese women in Korea have an elevated risk for developing chronic laryngitis. Further epidemiological and experimental studies are necessary to clarify the impact of obesity on this condition. PMID- 26138995 TI - A Novel Three-Way Variant t(8;13;21)(q22;q33;q22) in a Child with Acute Myeloid Leukemia with RUNX1/RUNX1T1 : The Contribution of Molecular Approaches for Revealing t(8;21) Variants. PMID- 26138996 TI - Reduction in disease progression by inhibition of transforming growth factor alpha-CCL2 signaling in experimental posttraumatic osteoarthritis. AB - OBJECTIVE: Transforming growth factor alpha (TGFalpha) is increased in osteoarthritic (OA) cartilage in rats and humans and modifies chondrocyte phenotype. CCL2 is increased in OA cartilage and stimulates proteoglycan loss. This study was undertaken to test whether TGFalpha and CCL2 cooperate to promote cartilage degradation and whether inhibiting either reduces disease progression in a rat model of posttraumatic OA. METHODS: Microarray analysis was used to profile expression of messenger RNA (mRNA) for Tgfa, Ccl2, and related genes in a rat model of posttraumatic OA. Rat primary chondrocytes and articular cartilage explants were treated with TGFalpha in the presence or absence of MEK-1/2, p38, phosphatidylinositol 3-kinase, Rho-associated protein kinase, or CCR2 inhibitors and immunostained for markers of cartilage degradation. The rat model was used to administer pharmacologic inhibitors of TGFalpha (AG1478) and CCL2 (RS504393) signaling for up to 10 weeks and assess histopathology and serum biomarkers of cartilage synthesis (C-propeptide of type II collagen [CPII]) and breakdown (C2C). RESULTS: Tgfa and Ccl2 mRNA were simultaneously up-regulated in articular cartilage in the rat model of posttraumatic OA. TGFalpha induced expression of CCL2, Mmp3, and Tnf in primary chondrocytes. Cleavage of type II collagen and aggrecan (by matrix metalloproteinases and ADAMTS-4/5, respectively) induced by TGFalpha was blocked by pharmacologic inhibition of CCL2 in cartilage explants. In vivo pharmacologic inhibition of TGFalpha or CCL2 signaling reduced Osteoarthritis Research Society International cartilage histopathology scores and increased serum CPII levels, but only TGFalpha inhibition reduced C2C levels intreated versus untreated rat OA cartilage. CONCLUSION: TGFalpha signaling stimulates cartilage degradation via a CCL2-dependent mechanism, but pharmacologic inhibition of the TGFalpha-CCL2 axis reduces experimental posttraumatic OA progression in vivo. PMID- 26138997 TI - Ibrutinib for the treatment of Waldenstrom macroglobulinemia. AB - Waldenstrom macroglobulinemia (WM) is a B-cell non-Hodgkin lymphoma (NHL) characterized by IgM monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Until recently, there was no drug specifically approved for WM by the US FDA, leading to wide variations in therapeutic strategies across the globe. Ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, is the first drug approved specifically for WM by the FDA after a clinical trial showed impressive response in previously treated WM. Ibrutinib is a non-stem cell toxic and non-neurotoxic option and suitable for long-term oral maintenance therapy, with the potential of improving survival in WM. With identification of novel genetic mutations impacting response to ibrutinib, it would be possible to individualize therapy based on MYD88 and CXCR4 genotypes. However, long-term safety and efficacy data are required, and cost-effectiveness needs to be addressed before ibrutinib can gain widespread acceptance for front-line therapy of WM. PMID- 26138998 TI - Detecting themes of public concern: a text mining analysis of the Centers for Disease Control and Prevention's Ebola live Twitter chat. AB - A diagnosis of Ebola on US soil triggered widespread panic. In response, the Centers for Disease Control and Prevention held a live Twitter chat to address public concerns. This study applied a textual analytics method to reveal insights from these tweets that can inform communication strategies. User-generated tweets were collected, sorted, and analyzed to reveal major themes. The public was concerned with symptoms and lifespan of the virus, disease transfer and contraction, safe travel, and protection of one's body. PMID- 26138999 TI - Clinical and economic impact of various strategies for varicella immunity screening and vaccination of health care personnel. AB - BACKGROUND: Exposure to patients with varicella or herpes zoster causes considerable disruption to a health care facility's operations and has a significant health and economic impact. However, practices related to screening for immunity and immunization of health care personnel (HCP) for varicella vary widely. METHODS: A decision tree model was built to evaluate the cost effectiveness of 8 different strategies of screening and vaccinating HCP for varicella. The outcomes are presented as probability of acquiring varicella, economic impact of varicella per employee per year, and cost to prevent additional cases of varicella. Monte Carlo simulations and 1-way sensitivity analyses were performed to address the uncertainties inherent to the model. Alternative epidemiologic and technologic scenarios were also analyzed. RESULTS: Performing a clinical screening followed by serologic testing of HCP with negative history diminished the cost impact of varicella by >99% compared with not having a program. Vaccinating HCP with negative screen cost approximately $50,000 per case of varicella prevented at the current level of U.S. population immunity, but was projected to be cost-saving at 92% or lower immunity prevalence. Improving vaccine acceptance rates and using highly sensitive assays also optimize cost-effectiveness. CONCLUSION: Strategies relying on screening and vaccinating HCP for varicella on employment were shown to be cost-effective for health care facilities and are consistent with current national guidelines for varicella prevention. PMID- 26139000 TI - Origin of methicillin-resistant Staphylococcus aureus health care-associated infections: evaluation of the role of anterior nares. AB - Methicillin-resistant Staphylococcus aureus (MRSA) health care-associated infections (HAIs) are a cause of extended hospitalizations and escalating health care costs. We typed 49 MRSA HAIs and their corresponding admission nasal MRSA isolates to determine strain-relatedness and better define the role of anterior nares in the causation of HAI and the value of decolonization. Based on repetitive extragenic palindromic sequencing polymerase chain reaction results, the majority of our patients possibly acquired MRSA HAI from nonnasal sources (36 out of 49; 74%). Among the remaining patients (13 out of 49; 26%) the nasal and clinical HAI isolates matched, indicating potential benefit of decolonization among this subsegment of patients. These findings may be relevant to institutions such as Veterans Health Administration hospitals that already have universal screening programs but are looking at ways to further reduce MRSA HAI incidence. PMID- 26139001 TI - Questionable validity of the catheter-associated urinary tract infection metric used for value-based purchasing. AB - Catheter-associated urinary tract infections (CAUTIs) occur in 290,000 US hospital patients annually, with an estimated cost of $290 million. Two different measurement systems are being used to track the US health care system's performance in lowering the rate of CAUTIs. Since 2010, the Agency for Healthcare Research and Quality (AHRQ) metric has shown a 28.2% decrease in CAUTI, whereas the Centers for Disease Control and Prevention metric has shown a 3%-6% increase in CAUTI since 2009. Differences in data acquisition and the definition of the denominator may explain this discrepancy. The AHRQ metric analyzes chart-audited data and reflects both catheter use and care. The Centers for Disease Control and Prevention metric analyzes self-reported data and primarily reflects catheter care. Because analysis of the AHRQ metric showed a progressive change in performance over time and the scientific literature supports the importance of catheter use in the prevention of CAUTI, it is suggested that risk-adjusted catheter-use data be incorporated into metrics that are used for determining facility performance and for value-based purchasing initiatives. PMID- 26139002 TI - Performances from the laboratory to improve the clinical use of cefepime. PMID- 26139003 TI - Comparison of estimated human dose of (68)Ga-MAA with (99m)Tc-MAA based on rat data. AB - OBJECTIVE: (99m)Tc macroaggregated albumin ((99m)Tc-MAA) that had been used as a perfusion agent has been evaluated. In this study, we tried to estimate human absorbed dose of 68Ga-MAA via commercially available kit from Pars-Isotopes, based on biodistribution data in wild-type rats, and compare our estimation with the available absorbed dose data from (99m)Tc-MAA. METHODS: For biodistribution of 68Ga-MAA, three rats were sacrificed at each selected times after injection (15, 30, 45, 60, and 120 min) and the percentage of injected dose per gram of each organ was measured by direct counting from rats data from 11 harvested organs. The medical internal radiation dose formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. RESULTS: The biodistribution data for 68Ga-MAA showed that the most of the activity was taken up by the lung (more than 97 %) in no time. Our dose prediction shows that a 185-MBq injection of 68Ga-MAA into humans might result in an estimated absorbed dose of 4.31 mGy in the whole body. The highest absorbed doses are observed in the adrenals, spleen, pancreas, and red marrow with 0.36, 0.34, 0.26, and 0.19 mGy, respectively. CONCLUSION: Since the (99m)Tc-MAA remains longer than 68Ga-MAA in the lung and 68Ga-MAA has good image qualities and results in lower amounts of dose delivery to the critical organs such as gonads, red marrow, and adrenals, the use of 68Ga-MAA is recommended. PMID- 26139004 TI - Twelve tips for medical students to maximise learning in theatre. PMID- 26139006 TI - Evaluation of a dentoalveolar model for testing mouthguards: stress and strain analyses. AB - BACKGROUND/AIM: Custom-fitted mouthguards are devices used to decrease the likelihood of dental trauma. The aim of this study was to develop an experimental bovine dentoalveolar model with periodontal ligament to evaluate mouthguard shock absorption, and impact strain and stress behavior. METHODS: A pendulum impact device was developed to perform the impact tests with two different impact materials (steel ball and baseball). Five bovine jaws were selected with standard age and dimensions. Six-mm mouthguards were made for the impact tests. The jaws were fixed in a pendulum device and impacts were performed from 90, 60, and 45 degrees angles, with and without mouthguard. Strain gauges were attached at the palatal surface of the impacted tooth. The strain and shock absorption of the mouthguards was calculated and data were analyzed with 3-way anova and Tukey's test (alpha = 0.05). Two-dimensional finite element models were created based on the cross-section of the bovine dentoalveolar model used in the experiment. A nonlinear dynamic impact analysis was performed to evaluate the strain and stress distributions. RESULTS: Without mouthguards, the increase in impact angulation significantly increased strains and stresses. Mouthguards reduced strain and stress values. CONCLUSIONS: Impact velocity, impact object (steel ball or baseball), and mouthguard presence affected the impact stresses and strains in a bovine dentoalveolar model. Experimental strain measurements and finite element models predicted similar behavior; therefore, both methodologies are suitable for evaluating the biomechanical performance of mouthguards. PMID- 26139007 TI - Severe right coronary artery injury during minimally invasive tricuspid valve repair. PMID- 26139005 TI - The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression. AB - OBJECTIVES: To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. METHODS: MTX-naive, early RA patients with <=12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. RESULTS: 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. CONCLUSIONS: In MTX naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. TRIAL REGISTRATION NUMBER: (NCT01451203). PMID- 26139008 TI - Impact of Early Invasive Approach on Outcomes of Patients With Acute Coronary Syndrome and Baseline Anemia: Analysis From the ACSIS Registry. AB - BACKGROUND: Anemia in patients with acute coronary syndromes (ACS) is strongly related to the increased risk of bleeding and mortality. Whether benefit of early invasive strategy exceeds the risk of bleeding in these patients is unknown. AIM: To assess impact of early coronary angiography on outcomes of patients with ACS and baseline anemia. METHODS AND RESULTS: Biennial Israeli ACS registry (ACSIS) prospectively collects data from all 26 public hospitals. The endpoints included rates of in-hospital major bleeding, as well as 30-day and 1-year mortality. Anemia at baseline was present in 1,464 of 5,600 patients with ACS (26.1%). Coronary angiography within index hospitalization was performed less frequently in patients with anemia (76.6% vs. 90.8%, P < 0.001). Non-performance of coronary angiography was associated with older age and higher prevalence of comorbidities. Among patients with anemia who underwent coronary angiography, the majority (95.5%) had obstructive coronary disease, of whom 77.8% were triaged to revascularization. Performance of coronary angiography was associated with significantly lower (P < 0.0001) rates of mortality at 30 days (5.7% vs. 15.6%) and at 1 year (11.9% vs. 34.1%). Major bleeding occurred with similar incidence in groups with and without coronary angiography (3.1% vs. 3.8%, respectively; P = 0.54). By multivariable analysis, performance of coronary angiography was an independent predictor of lower 1-year mortality (hazard ratio [95%CI] = 0.30 [0.21, 0.44]. CONCLUSION: In the setting of ACS, despite the presence of baseline anemia, early coronary angiography with subsequent revascularization, when indicated, was associated with improved clinical outcomes including 1-year mortality without significant increase in rates of major bleeding. PMID- 26139009 TI - "So prohibition can work?" Changes in use of novel psychoactive substances among adolescents attending a drug and alcohol treatment service following a legislative ban. PMID- 26139010 TI - DNA methylation as a potential diagnosis indicator for rapid discrimination of rare cancer cells and normal cells. AB - The global DNA methylation degree may be a ubiquitous and early biomarker to distinguish cancer cells from benign cells. However, its usefulness in clinical diagnosis was scarcely demonstrated, because the cancer cells isolated from patients were usually very rare. Even if 10 mL of peripheral blood was sampled from a patient, only tens of cancer cells could be isolated. So a method to quantify DNA methylation from small number of cells was needed to apply DNA methylation in clinical environment. In this study, we found that normal breast cell line MCF10A and breast cancer cell line MCF7 cells present significantly different percentage of genomic 5-methylcytosine (p < 0.02, n = 8), it could be a potential indicator for rapid discrimination of rare cancer cells from normal cells. However, conventional mass spectrometry needs usually ~10(6) cells to quantify DNA methylation degree, which was too large to be applied in clinical diagnosis. Here we developed a fast mass spectrometry-based method capable of analyzing the DNA methylation degree from only ~100 human cells. Our method could reveal the different DNA methylation degree between MCF10A and MCF7 cells in less than two hours, having the potential to provide reliable information for clinical application. PMID- 26139011 TI - Ultrathin inorganic molecular nanowire based on polyoxometalates. AB - The development of metal oxide-based molecular wires is important for fundamental research and potential practical applications. However, examples of these materials are rare. Here we report an all-inorganic transition metal oxide molecular wire prepared by disassembly of larger crystals. The wires are comprised of molybdenum(VI) with either tellurium(IV) or selenium(IV): {(NH4)2[XMo6O21]}n (X=tellurium(IV) or selenium(IV)). The ultrathin molecular nanowires with widths of 1.2 nm grow to micrometre-scale crystals and are characterized by single-crystal X-ray analysis, Rietveld analysis, scanning electron microscopy, X-ray photoelectron spectroscopy, ultraviolet-visible spectroscopy, thermal analysis and elemental analysis. The crystals can be disassembled into individual molecular wires through cation exchange and subsequent ultrasound treatment, as visualized by atomic force microscopy and transmission electron microscopy. The ultrathin molecular wire-based material exhibits high activity as an acid catalyst, and the band gap of the molecular wire-based crystal is tunable by heat treatment. PMID- 26139012 TI - Palladium/Copper-Cocatalyzed Oxidative Amidobrominations of Alkenes. AB - In the presence of LiBr, a palladium/copper combination catalyzes dehydrogenative amidobrominations of acrylates with NH-sulfoximines, leading to N-vinylated products by dual NH/CH coupling, followed by oxidative enamide bromination. Mechanistically, the domino process is proposed to involve palladium(II) species as key intermediates. First synthetic applications of the products have been demonstrated. PMID- 26139013 TI - Unexpected coupling between flow and adsorption in porous media. AB - We study the interplay between transport and adsorption in porous systems under a fluid flow, based on a lattice Boltzmann scheme extended to account for adsorption. We performed simulations on well-controlled geometries with slit and grooved pores, investigating the influence of adsorption and flow on dispersion coefficient and adsorbed density. In particular, we present a counterintuitive effect where fluid flow induces heterogeneity in the adsorbate, displacing the adsorption equilibrium towards downstream adsorption sites in grooves. We also present an improvement of the adsorption-extended lattice Boltzmann scheme by introducing the possibility for saturating Langmuir-like adsorption, while earlier work focused on linear adsorption phenomena. We then highlight the impact of this change in situations of high concentration of adsorbate. PMID- 26139014 TI - SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA induced murine acute asthma model. AB - BACKGROUND: c-Jun N-terminal kinase (JNK) relays extracellular stimuli through phosphorylation cascades that lead to various cell responses. In the present study, we aimed to investigate the effect of the JNK inhibitor SP600125 on the resolution of airway inflammation, and the underlying mechanism using a murine acute asthma model. METHODS: Female C57BL/6 mice were sensitized with saline or ovalbumin (OVA) on day 0, and challenged with OVA on day 14-20. Meanwhile, some of the mice were treated with SP600125 (30 mg/kg) intraperitoneally 2 h before each challenge. The airway inflammation was evaluated by counting the numbers of various types of inflammatory cells in bronchoalveolar lavage fluid (BALF), histopathology, cytokines production and mucus secretion in individual mouse. In addition, we analyzed the protein levels of phosphorylated JNK and TLR9 in the lung tissues. RESULTS: SP600125 markedly reduced the invasion of inflammatory cells into the peribronchial regions, and decreased the numbers of eosinophils, monocytes, neutrophils and lymphocytes in BALF. SP600125 also reduced the level of plasma OVA-specific IgE, lowered the production of pro-inflammatory cytokines in BALF and alleviated mucus secretion. Meanwhile, SP600125 inhibited OVA induced, increased expression of p-JNK and TLR9 in the lung tissues. CONCLUSIONS: Collectively, our data demonstrated that SP600125 promoted resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model. The JNK TLR9 pathway may be a new therapeutic target in the treatment for the allergic asthma. PMID- 26139015 TI - All-organic electrostrictive polymer composites with low driving electrical voltages for micro-fluidic pump applications. AB - This paper focuses on the improvement of a relaxor ferroelectric terpolymer, i.e., poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) [P(VDF TrFE-CFE)], filled with a bis(2-ethylhexyl) phthalate (DEHP). The developed material gave rise to a significantly increased longitudinal electrostrictive strain, as well as an increased mechanical energy density under a relatively low electric field. These features were attributed to the considerably enhanced dielectric permittivity and a decreased Young modulus as a result of the introduction of only small DEHP plasticizer molecules. In addition, the plasticizer-filled terpolymer only exhibited a slight decrease of the dielectric breakdown strength, which was a great advantage with respect to the traditional polymer-based electrostrictive composites. More importantly, the approach proposed herein is promising for the future development and scale-up of new high performance electrostrictive dielectrics under low applied electrical fields through modification simply by blending with a low-cost plasticizer. An experimental demonstration based on a flexible micro-fluidic application is described at the end of this paper, confirming the attractive characteristics of the proposed materials as well as the feasibility of integrating them as micro actuators in small-scale devices. PMID- 26139016 TI - Spinal cord progressive multifocal leukoencephalopathy detected premortem by MRI. PMID- 26139017 TI - HSV encephalitis-induced anti-NMDAR encephalitis in a 67-year-old woman: report of a case and review of the literature. AB - Herpes simplex virus (HSV) encephalitis can induce an autoimmune encephalitis mediated by autoantibodies against the N-methyl-D-aspartate receptor (NMDAR). Post-HSV NMDAR encephalitis and de novo NMDAR encephalitis have been more commonly described in children and young adults. We describe the case of a 67 year-old woman with post-HSV NMDAR encephalitis and review the relevant literature. Clinical, serological, neurophysiological, and imaging evaluations were undertaken in the evaluation of this patient. A literature review was performed. Nearly 2 months after a typical course of HSV encephalitis confirmed by HSV polymerase chain reaction studies from the spinal fluid and treated with intravenous acyclovir, a 67-year-old woman suffered neurological deterioration. There was no evidence of active HSV infection, but NMDAR antibodies were found in her serum and spinal fluid. The patient improved after initiation of immunosuppressive therapy. All patients who experience new or recurrent neurological symptoms following recovery from HSV encephalitis should be evaluated for post-infectious autoimmune encephalitis, including NMDAR encephalitis. PMID- 26139018 TI - Mind-altering microbes. PMID- 26139019 TI - Elevated rates of mild cognitive impairment in HIV disease. AB - With the rising number of individuals in their 50s and 60s who are infected with HIV, concerns have emerged about possible increases in the rates of non-HIV associated dementias. The current study examined the prevalence of mild cognitive impairment (MCI) in older HIV-infected adults, since MCI is an intermediate state between typical cognitive aging and dementia that emerges in this age range. Participants included 75 adults with HIV disease aged 50 years and older who were on combination antiretroviral therapy (cART) and had undetectable plasma viral loads and 80 demographically similar HIV-seronegative comparison subjects. Participants completed a research neuropsychological evaluation that was used to classify MCI according to the comprehensive diagnostic scheme described by Bondi et al. (J Alzheimers Dis 42:275-289, 2014). HIV-infected persons were over seven times more likely to have an MCI designation (16 %) than their seronegative counterparts (2.5 %). Within the HIV+ cohort, MCI had minimal overlap with diagnoses of asymptomatic neurocognitive impairment and was significantly associated with older age, lower Karnofsky Scale of Performance Scores, and mild difficulties performing instrumental activities of daily living (iADLs). HIV infection in older adults is associated with a notably elevated concurrent risk of MCI, which may increase the likelihood of developing non-HIV-associated dementias as this population ages further. PMID- 26139020 TI - Idiopathic myointimal hyperplasia of the mesenteric veins: a rare differential to be considered in idiopathic colitis. PMID- 26139021 TI - Pulmonary enteric adenocarcinoma. AB - A 70-year-old man was referred to our department due to abnormal shadows on a chest radiograph. Computed tomography of the chest revealed a 3-cm nodule in the right middle lung lobe, and bronchoscopy revealed adenocarcinoma cells with EGFR mutations. A lung resection was performed. Histological analysis revealed tumors comprising tall columnar cells that were similar to an adenocarcinoma of the sigmoid colon that had been resected 13 years previously. Metastatic colorectal carcinoma was initially considered, but immunohistochemical staining indicated pulmonary enteric adenocarcinoma. Pulmonary enteric adenocarcinoma was first described in 1991, and about 30 cases have since been described in the English literature. However, its concept and etiology are not clear. It is important to distinguish pulmonary enteric adenocarcinoma from metastatic colorectal carcinoma because of obvious differences in therapeutic strategies and prognosis, especially with a past history of colorectal carcinoma. Immunohistochemical and gene mutation analyses seemed to be helpful. PMID- 26139024 TI - Biomarkers for Alzheimer's disease: a controversial topic. PMID- 26139023 TI - The interface between delirium and dementia in elderly adults. AB - Delirium and dementia are two of the most common causes of cognitive impairment in older populations, yet their interrelation remains poorly understood. Previous studies have shown that dementia is the leading risk factor for delirium and that delirium is an independent risk factor for subsequent development of dementia. However, a major area of controversy is whether delirium is simply a marker of vulnerability to dementia, whether the effect of delirium is solely related to its precipitating factors, or whether delirium itself can cause permanent neuronal damage and lead to dementia. Ultimately, all of these hypotheses are likely to be true. Emerging evidence from epidemiological, clinicopathological, neuroimaging, biomarker, and experimental studies lends support to a strong relation between delirium and dementia, and to both shared and distinct pathological mechanisms. New preventive and therapeutic approaches that target delirium might offer a sought-after opportunity for early intervention, preservation of cognitive reserve, and prevention of irreversible cognitive decline in ageing. PMID- 26139025 TI - Fontan conversion with hepatic vein exclusion: a means for hepatic preservation in single ventricle heart disease. AB - Patients with single ventricle heart disease often undergo staged surgical palliation, ultimately resulting in Fontan anatomy and physiology. Long-term consequences include cirrhosis of the liver, protein-losing enteropathy, and premature death. Elevated central venous pressure and venous congestion transmitted to the abdominal viscera have been implicated in the aetiology of many of these complications. We present a novel operation directed at protecting the liver and intestines by excluding the splanchnic venous return from the Fontan pathway. Instead of exposure to elevated Fontan pressures, the liver and intestines will be exposed to lower common atrial pressures. We hope that this modification will minimise the abdominal complications of Fontan anatomy and physiology. PMID- 26139022 TI - Longitudinal assessment of neuroimaging and clinical markers in autosomal dominant Alzheimer's disease: a prospective cohort study. AB - BACKGROUND: The biomarker model of Alzheimer's disease postulates a dynamic sequence of amyloidosis, neurodegeneration, and cognitive decline as an individual progresses from preclinical Alzheimer's disease to dementia. Despite supportive evidence from cross-sectional studies, verification with long-term within-individual data is needed. METHODS: For this prospective cohort study, carriers of autosomal dominant Alzheimer's disease mutations (aged >=21 years) were recruited from across the USA through referrals by physicians or from affected families. People with mutations in PSEN1, PSEN2, or APP were assessed at the University of Pittsburgh Alzheimer's Disease Research Center every 1-2 years, between March 23, 2003, and Aug 1, 2014. We measured global cerebral amyloid beta (Abeta) load using (11)C-Pittsburgh Compound-B PET, posterior cortical metabolism with (18)F-fluorodeoxyglucose PET, hippocampal volume (age and sex corrected) with T1-weighted MRI, verbal memory with the ten-item Consortium to Establish a Registry for Alzheimer's Disease Word List Learning Delayed Recall Test, and general cognition with the Mini Mental State Examination. We estimated overall biomarker trajectories across estimated years from symptom onset using linear mixed models, and compared these estimates with cross-sectional data from cognitively normal control individuals (age 65-89 years) who were negative for amyloidosis, hypometabolism, and hippocampal atrophy. In the mutation carriers who had the longest follow-up, we examined the within-individual progression of amyloidosis, metabolism, hippocampal volume, and cognition to identify progressive within-individual changes (a significant change was defined as an increase or decrease of more than two Z scores standardised to controls). FINDINGS: 16 people with mutations in PSEN1, PSEN2, or APP, aged 28-56 years, completed between two and eight assessments (a total of 83 assessments) over 2-11 years. Significant differences in mutation carriers compared with controls (p<0.01) were detected in the following order: increased amyloidosis (7.5 years before expected onset), decreased metabolism (at time of expected onset), decreased hippocampal volume and verbal memory (7.5 years after expected onset), and decreased general cognition (10 years after expected onset). Among the seven participants with longest follow-up (seven or eight assessments spanning 6-11 years), three individuals had active amyloidosis without progressive neurodegeneration or cognitive decline, two amyloid-positive individuals showed progressive neurodegeneration and cognitive decline without further progressive amyloidosis, and two amyloid-positive individuals showed neither active amyloidosis nor progressive neurodegeneration or cognitive decline. INTERPRETATION: Our results support amyloidosis as the earliest component of the biomarker model in autosomal dominant Alzheimer's disease. Our within-individual examination suggests three sequential phases in the development of autosomal dominant Alzheimer's disease-active amyloidosis, a stable amyloid-positive period, and progressive neurodegeneration and cognitive decline-indicating that Abeta accumulation is largely complete before progressive neurodegeneration and cognitive decline occur. These findings offer supportive evidence for efforts to target early Abeta deposition for secondary prevention in individuals with autosomal dominant Alzheimer's disease. FUNDING: National Institutes of Health and Howard Hughes Medical Institute. PMID- 26139026 TI - High genetic diversity and population structure in the endangered Canarian endemic Ruta oreojasme (Rutaceae). AB - Insular species are expected to have low genetic diversity, for their populations are often small and isolated, and characterized by restricted gene flow and increased incidence of inbreeding. However, empirical results do not always match this expectation. For example, population genetic analyses of several Canarian endemics, based mainly on allozymes, show levels of genetic diversity exceptionally high for insular species. To investigate whether genetic variation in rare species endemic to Canary Islands is low, as predicted by theoretical expectations, or high, as documented in some previous studies, we analysed genetic diversity of the endangered Ruta oreojasme, a rare endemic of the island of Gran Canaria, using microsatellite markers, which are more variable than allozymes. Our analyses identified very high levels of genetic diversity (A = 7.625, P = 0.984, H o = 0.558, H e = 0.687) for R. oreojasme. Even though the distribution of the species is restricted to the South of Gran Canaria, only one population shows low genetic diversity, isolation and signs of a recent bottleneck/founder event. Some intrinsic characteristics of R. oreojasme (hermaphroditism, proterandry and polyploidy), the relative climatic stability of the Canarian archipelago during Quaternary glacials/interglacials, the size of most populations (thousands of individuals), its age, and the relative proximity of the archipelago to the mainland might have contributed to the high diversity that characterises this endemic. As expected, given the marked topographic complexity of Gran Canaria, we found marked genetic structure in R. oreojasme populations. Our results support the observation that Canarian endemics are characterised by unexpectedly high genetic diversity and provides important insights for potential applications to the conservation of R. oreojasme. PMID- 26139027 TI - Hidradenitis Suppurativa/Acne Inversa: Criteria for Diagnosis, Severity Assessment, Classification and Disease Evaluation. AB - BACKGROUND: Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating disease, which inflicts a significant burden on patients and is associated with comorbid disorders, such as significantly reduced quality of life, depression, stigmatization, inactivity, working disability, impairment of sexual health and several cardiovascular risk factors. AIMS/METHODS: To implement an expert consensus on the diagnostic criteria, severity and classification assessment, and an assessment of anti inflammatory treatment effectiveness based on current evidence. RESULTS: This article provides criteria for diagnosis, severity assessment, classification and evaluation of HS patients. CONCLUSION: The provided criteria can be used as tools for the promotion of uniformity in HS evaluation and facilitation of early and timely identification and referral in the primary care setting and thorough and efficient evaluation in daily clinical practice. PMID- 26139028 TI - Extensions and applications of the A24 data set of accurate interaction energies. AB - The A24 data set (Rezac and Hobza, J. Chem. Theory Comput. 2013, 9, 2151-2155) is a set of noncovalent complexes large enough to showcase various types of interactions yet small enough to make highly accurate calculations possible. It is intended for the testing of accurate computational methods which are then used as a benchmark in larger model systems. In this work, we improve the best estimate of the interaction energies in the set by updating their CCSD(T)/CBS and CCSDT(Q) components with calculations in larger basis sets. The data set is then used to test a large number of composite CCSD(T) approaches. Special attention is paid to the use of the explicitly correlated MP2-F12 method in these composite calculations. It is shown that an accuracy of 1-2% can be achieved with setups applicable to larger molecules. The effect of frozen natural orbital approximation on the accuracy of composite CCSD(T)/CBS calculations is also quantified. In four trivially saturated complexes where CCSDT(Q)/CBS data are now available, the convergence of the many-body correlation effects is assessed by fixed-node diffusion Monte Carlo (FN-DMC) calculations. A good agreement is achieved between FN-DMC and high-level coupled-cluster which represents an important cross-check of both approaches. PMID- 26139029 TI - Constant change: dynamic regulation of membrane transport by calcium signalling networks keeps plants in tune with their environment. AB - Despite substantial variation and irregularities in their environment, plants must conform to spatiotemporal demands on the molecular composition of their cytosol. Cell membranes are the major interface between organisms and their environment and the basis for controlling the contents and intracellular organization of the cell. Membrane transport proteins (MTPs) govern the flow of molecules across membranes, and their activities are closely monitored and regulated by cell signalling networks. By continuously adjusting MTP activities, plants can mitigate the effects of environmental perturbations, but effective implementation of this strategy is reliant on precise coordination among transport systems that reside in distinct cell types and membranes. Here, we examine the role of calcium signalling in the coordination of membrane transport, with an emphasis on potassium transport. Potassium is an exceptionally abundant and mobile ion in plants, and plant potassium transport has been intensively studied for decades. Classic and recent studies have underscored the importance of calcium in plant environmental responses and membrane transport regulation. In reviewing recent advances in our understanding of the coding and decoding of calcium signals, we highlight established and emerging roles of calcium signalling in coordinating membrane transport among multiple subcellular locations and distinct transport systems in plants, drawing examples from the CBL CIPK signalling network. By synthesizing classical studies and recent findings, we aim to provide timely insights on the role of calcium signalling networks in the modulation of membrane transport and its importance in plant environmental responses. PMID- 26139030 TI - Follow-up (99m)Tc EC renal dynamic scintigraphy and DMSA-III SPECT/CT in unmasking a masqueraded case of Horseshoe kidney. AB - Hydronephrosis is a common finding in urinary tract outflow obstruction. Chronically obstructed hydronephrotic system may be associated with parenchymal changes. Ultrasound, intravenous urography, micturating cysto-urethrogram and scintigraphy are commonly performed to evaluate the cause of obstruction. In childhood, pelviureteric junction obstruction is a common cause of the hydronephrosis. Hydronephrosis can also be present in horseshoe kidneys due to poor drainage. However, a large sized hydronephrotic cavity may obscure the finding of horseshoe kidney. A case was reported, and it was diagnosed as horseshoe kidney on follow-up renal dynamic scan and confirmed with the help of dimercaptosuccinic acid SPECT/CT. PMID- 26139031 TI - Diagnostic dilemma of urinary leak vs. perirenal abscess on skeletal scintigraphy: The added value of SPECT/CT and renal scintigraphy. PMID- 26139032 TI - [Total isolated anomalous pulmonary venous return: Are there any clues for prenatal screening?]. AB - Total anomalous pulmonary venous connection (TAPVC) is a serious congenital anomaly. TAPVC with obstruction of pulmonary venous return is an emergency requiring urgent intervention. Before 2010, very few isolated TAPVC were diagnosed prenatally. It has been suggested in the past literature that the use of Color flow Doppler is particularly useful for the screening of TAPVC prenatally. In fact, although color-Doppler is often useful to confirm a TAPVC diagnosis, it can be quite misleading in the screening process of the condition. Looking at data of missed TAPVC, we describe how to identify TAPVC during routine cardiac screening. Since 2010, our isolated TAPVC prenatal diagnosis rate is more than 40%. PMID- 26139033 TI - The geographic distribution of cases of Crimean-Congo hemorrhagic fever: Kastamonu, Turkey. AB - The purpose of this study was to analyze the epidemiological characteristics of cases diagnosed with Crimean-Congo Hemorrhagic Fever (CCHF) with the help of Geographic Information Systems (GIS) and to establish an epidemiological risk map. Data for 434 cases diagnosed with CCHF between 01.01.2004 and 31.12.2013 were subjected to statistical analysis SPSS 13.0 software. A digital map of Kastamonu was transferred onto ArcGIS 10.0 software in order to establish a risk map for CCHF. The highest cumulative incidence of CCHF is 41.29/10,000, and in people living at altitudes of 1001-1200 meters. ROC analysis of altitudes above sea level of residences with CCHF cases revealed an area under the curve of 74.5% (95% CI: 0.72-0.76, p<0.05). At a cut-off point of 836.5 meters, sensitivity was 0.74 and specificity 0.76. Cumulative incidence of CCHF was significantly positively correlated with number of animals per head (r=0.76) and area of agricultural land per head (r=0.59) (p<0.05). No significant correlation was determined between cumulative incidence and forested area percentages. This study reveals that both men and women living at more than 836.5 meters above sea level and working in agriculture and animal husbandry are at risk of CCHF between May and July. Detailed examination of the ecology of vector ticks is now needed in order to fully determine the epidemiology of the disease. PMID- 26139034 TI - [Use of pessaries to prevent preterm birth: Are we going back to mechanical devices in obstetrics?]. AB - AIM: To review the available data in the literature on the use of pessaries in preventing preterm birth. MATERIALS AND METHODS: We searched PubMed and the Cochrane library with pessary preterm birth. RESULTS: Fifty-eight papers were identified, most of them with little scientific value. A randomized study, including 385 singleton pregnancies with a transvaginal ultrasound cervical length less than 25 mm between 18 and 22 WG, shows a reduction of spontaneous prematurity before 34 WG in the pessary group, with an OR of 0.18 (95%CI: 0.08 0.37). Another study on multiple pregnancies randomized between 12 and 20 WG, with a cervix measured by ultrasound between 16 and 22 WG, showed a reduction of neonatal morbidity in the pessary group (RR: 0.42; 95%CI: 0.19-0.91) in a sub group with a cervical length<38 mm. CONCLUSIONS: These first results from randomized controlled study are encouraging. Other studies on singleton and twin pregnancies are ongoing or about to start. PMID- 26139035 TI - [Maternal obesity and pregnancy: Evolution of prevalence and of place of birth]. AB - OBJECTIVE: The primary objective was to describe the evolution of the prevalence of maternal obesity in France. The secondary objectives were to assess changes in the French regions and the place of birth according to type (public/private) and level of care. MATERIAL AND METHODS: Study based population of all births between 1999 and 2009 included in the AUDIPOG database. Our judgment criterion was the body mass index (BMI) divided into classes. RESULTS: Seventy-four thousand and forty-six pregnancies were included. The mean BMI was 22.9+/-4.5kg/m(2) with an increase between 1999-2001 and 2008-2009 (22.6+/-4.3kg/m(2) versus 23.1+/ 4.7kg/m(2), P<10(-4)). North was the first region in terms of overweight patients (18%) and obese (10.2%). There was an increase of the birth rate in public maternity, and level II and III regardless of BMI class. Only the class of patients with a BMI >=40kg/m(2) delivered more frequently in level III with an increase between the first and the last period of the study (20.8% versus 36.8%, P=0.02). CONCLUSION: The BMI is still increasing with more and more patients with a BMI >=40kg/m(2) referred to level III. This raises the question of the organization of care and follow-up of these patients. PMID- 26139036 TI - [Prediction of spontaneous preterm birth in symptomatic patients: A review]. AB - OBJECTIVE OF THE REVIEW: To identify predictors of preterm delivery in the context of threatened preterm labour. MAIN POINTS: Tobacco use and previous history of preterm delivery are the main anamnestic elements to predict preterm birth. High positive predictive value of vaginal examination is restricted to cases with strong cervical alterations like dilatation over 4 cm. In case of discrete cervical alterations, literature confirms the great interest for cervical length ultrasonographic measurement as it reduces false positive cases. Absence of fetal respiratory movements appears to be as sensitive as cervical length and could be more specific but its clinical use remains rare. Vaginal detection of fetal fibronectin is the most useful biomarker with high negative predictive value (>90%). Fibronectin quantitative test seems to enhance the positive predictive value. No other biomarker is currently used in clinical practice. Electromyography and elastography of the cervix appear to be promising approaches. PMID- 26139037 TI - [Delivery of premature infants]. AB - Prematurity is a frequent event and clearly raises an issue concerning how these fetuses with multiple weaknesses should be delivered. Although, a systematic abdominal approach has no scientific basis, there are cases where the caesarean is chosen because of other factors associated to prematurity such as any maternal or fetal indication to terminate the pregnancy while labour induction remains impossible. However, in case of breech presentation, which is often delivered by caesarean, the literature does recommend neither the vaginal nor the abdominal approach. Caesarean in case of prematurity is more difficult because of the absence of any inferior segment and implies making a large incision so as to easily extract these weak fetuses. Increased maternal morbidity related to preterm caesarean sections has been reported through out literature. The viability gestational age limit represents a confounding factor in most studies since caesarean is rarely chosen for these fetuses because of a very low expected survival rate, while it is probably in this situation that the abdominal approach could provide a real benefit. Larger studies are required to show potential advantages. Systematic use of episiotomies or instrumental deliveries in case of vaginal births is not recommended in case of prematurity. Protecting the fetal head with spatulas still requires further evaluations. PMID- 26139038 TI - Donders is dead: cortical traveling waves and the limits of mental chronometry in cognitive neuroscience. AB - An assumption nearly all researchers in cognitive neuroscience tacitly adhere to is that of space-time separability. Historically, it forms the basis of Donders' difference method, and to date, it underwrites all difference imaging and trial averaging of cortical activity, including the customary techniques for analyzing fMRI and EEG/MEG data. We describe the assumption and how it licenses common methods in cognitive neuroscience; in particular, we show how it plays out in signal differencing and averaging, and how it misleads us into seeing the brain as a set of static activity sources. In fact, rather than being static, the domains of cortical activity change from moment to moment: Recent research has suggested the importance of traveling waves of activation in the cortex. Traveling waves have been described at a range of different spatial scales in the cortex; they explain a large proportion of the variance in phase measurements of EEG, MEG and ECoG, and are important for understanding cortical function. Critically, traveling waves are not space-time separable. Their prominence suggests that the correct frame of reference for analyzing cortical activity is the dynamical trajectory of the system, rather than the time and space coordinates of measurements. We illustrate what the failure of space-time separability implies for cortical activation, and what consequences this should have for cognitive neuroscience. PMID- 26139039 TI - Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function? AB - PURPOSE: To compare the impact of proximal or distal splenic artery embolisation versus that of splenectomy on splenic immune function as measured by IgM memory B cell levels. MATERIALS AND METHODS: Patients with splenic trauma who were treated by splenic artery embolisation (SAE) were enrolled. After 6 months splenic volume was assessed by CT, and IgM memory B cells in peripheral blood were measured and compared to a local normal reference population and to a post-splenectomy population. RESULTS: Of the 71 patients who underwent embolisation, 38 underwent proximal embolisation, 11 underwent distal embolisation, 22 patients were excluded, 1 had both proximal and distal embolisation, 5 did not survive and 16 did not return for evaluation. There was a significant difference between splenectomy and proximal or distal embolisation and a trend towards greater preservation of IgM memory B cell number in those with distal embolisation-a difference that could not be attributed to differences in age, grade of injury or residual splenic volume. CONCLUSION: IgM memory B cell levels are significantly higher in those treated with SAE compared to splenectomy. Our data provide evidence that splenic embolisation should reduce immunological complications of spleen trauma and suggest that distal embolisation may maintain better function. PMID- 26139040 TI - Complete denture fabrication with CAD/CAM record bases. AB - One of the primary goals of new materials and processes for complete denture fabrication has been to reduce polymerization shrinkage. The introduction of computer-aided design and computer-aided manufacturing (CAD/CAM) technology into complete denture fabrication has eliminated polymerization shrinkage in the definitive denture. The use of CAD/CAM record bases for complete denture fabrication can provide a better-fitting denture with fewer postprocessing occlusal errors. PMID- 26139041 TI - Fracture resistance of lithium disilicate restorations after endodontic access preparation: An in vitro study. AB - STATEMENT OF PROBLEM: Endodontic access preparation through a lithium disilicate restoration is a frequently encountered clinical situation. The common practice of repairing the accessed crown with composite resin may result in a weakened restoration. PURPOSE: The purpose of this in vitro study was to determine the effect of endodontic access preparation on the fracture resistance and microstructural integrity of monolithic pressed and monolithic milled lithium disilicate complete coverage restorations. MATERIAL AND METHODS: Twenty monolithic pressed (IPS e.max Press) and 20 monolithic milled (IPS e.max CAD) lithium disilicate restorations were fabricated. Ten of the pressed and 10 of the milled crowns were accessed for a simulated endodontic treatment and subsequently repaired by using a porcelain repair system and composite resin. All specimens were submitted to cyclic loading and then loaded to failure. Force data were recorded and analyzed with 2-way ANOVA followed by a post hoc test (Sidak correction) to indicate significant differences among the groups (alpha=.05). A Weibull analysis was also performed for each group. Eight (4 pressed and 4 milled) additional restorations were fabricated to complete a scanning electron microscope (SEM) analysis and evaluate the surface damage created by the endodontic access preparation. RESULTS: A statistically significant difference (P=.019) was found between the pressed intact and pressed repaired restorations and between the pressed intact and milled repaired restorations (P=.002). Specimens that were examined with an SEM showed edge chipping involving primarily the glaze layer around the access openings. CONCLUSIONS: Endodontic access preparation of lithium disilicate restorations resulted in a significantly reduced load to failure in the pressed specimens, but not in the milled specimens. PMID- 26139042 TI - Maxillary definitive impression of excessively movable tissue with a single material. PMID- 26139043 TI - In vitro comparison of the maxillary occlusal plane orientation obtained with five facebow systems. AB - STATEMENT OF PROBLEM: The sagittal and coronal orientation of the maxillary occlusal plane plays an important role in the esthetic and functional outcome of dental prostheses. The accuracy of contemporary facebow transfer systems in transferring this orientation to semiadjustable articulators has not been quantified. PURPOSE: The purpose of this in vitro investigation was to analyze the sagittal and coronal orientation of the occlusal plane with 5 different facebow transfer systems. MATERIAL AND METHODS: A phantom head containing a maxillary typodont (control) was oriented so that the Frankfort horizontal plane was horizontal. The angle between the occlusal plane of the maxillary arch of the phantom head and the Frankfort horizontal plane was measured along the sagittal and coronal planes with a digital protractor. Fifteen facebow records using each of 5 facebow transfer systems (test groups) were made on the phantom head containing the maxillary typodont. Diagnostic casts of the maxillary typodont were mounted on semi-adjustable arcon articulators from the facebow records. The same angles measured on the control were measured on the test groups. These angles were compared with the same angle measured on the maxillary arch of the phantom head (control). All measurements were made by 2 operators. RESULTS: Significant differences in the sagittal and coronal orientation of the occlusal plane were noted. Compared with the control, the Denar system had the least significant difference in the coronal orientation of the occlusal plane, while the Pana-Mount system had the least significant difference in the sagittal orientation of the occlusal plane. An intergroup comparison of the test groups showed significant differences among the groups. The Kois system showed the greatest difference in the coronal plane orientation, while the Denar system showed the greatest difference in the sagittal plane orientation. CONCLUSIONS: None of the tested facebow systems exactly replicated the sagittal and coronal orientation of the maxillary occlusal plane. Significant differences in the sagittal and coronal orientation of the occlusal plane were observed between the test groups and the control. Intergroup comparisons revealed significant differences in the sagittal and coronal orientation of the occlusal plane. PMID- 26139044 TI - Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance. AB - Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases. PMID- 26139045 TI - Transient retinal artery occlusion: the potential utility and limitations of electroretinography. PMID- 26139046 TI - Electroretinography can provide objective assessment of inner retinal function prior to atrophic change on OCT. PMID- 26139047 TI - Stability and safety of MA50 intraocular lens placed in the sulcus. AB - PURPOSE: To describe the safety and stability of sulcus placement of the MA50 intraocular lens (IOL). PATIENTS AND METHODS: Consecutive patients with MA50 IOLs placed in the sulcus at the University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA, from 1997 to 2012 were identified. Inclusion criteria included patients with over 4 weeks of follow-up data. AEL was compared with incidence of IOL decentration using at two-tailed Student's t-test. RESULTS: Fifty eyes of 49 patients meeting the inclusion criteria were identified. Four weeks post operatively, the average best-corrected visual acuity was 20/30. IOL decentration occurred in 14% of patients; patients with decentered IOLs had a significantly longer average AEL (25.37 mm) than patients whose IOL remained centered (23.94 mm, P=0.017). Other complications included uveitis-glaucoma-hyphema syndrome (12%), iritis (8%), and glaucoma (6%). There were no cases of pigment dispersion syndrome or need for lens exchange. Twelve eyes (24%) had intra-operative optic capture by the anterior capsule, none of which had post-operative decentration. CONCLUSION: The MA50 IOL is a reasonable, stable option for placement in the sulcus, with a low-risk profile; however, in eyes with longer AEL and presumably larger anterior segment, surgeons should consider placing an IOL with longer haptic distance than the MA50 to maintain centration. Optic capture of the MA50 IOL by the anterior capsule should be considered for longer eyes, as it is protective against decentration. PMID- 26139048 TI - Spectral-domain optical coherence tomography analysis of persistent subretinal fluid after scleral buckling surgery for macula-off retinal detachment. AB - PURPOSE: To determine the predictive value of markers for persistent subretinal fluid (SRF) absorption and the influence of subfoveal fluid on visual outcome after scleral buckle (SB) surgery for rhegmatogenous retinal detachment (RRD). PATIENTS AND METHODS: This was a retrospective, observational study. We reviewed the medical records of 64 eyes of 64 patients who underwent SB surgery for macula off RRD. Patients underwent clinical examination and spectral-domain optical coherence tomography before surgery, at 1 month and every 3 months postoperatively. The height and width of SRF bleb(s) were measured over time. RESULTS: Persistent SRF at 1 month was observed in 40 eyes (62.5%). SRF blebs were first detected 1.7 +/- 2.2 months postoperatively. In 29 cases that could be fully followed up, SRF blebs were completely absorbed 7.8 +/- 4.4 months postoperatively. Resolution of fluid was associated with an improvement of VA (P = 0.003). Serial measurements of SRF bleb size showed that bleb width decreased significantly at all time points during the 12-month follow-up period (P < 0.05), while significant bleb height decrease occurred from postoperative sixth month only (P < 0.05). There was no correlation between VA outcomes and subfoveal bleb height or width (P > 0.05). The cut-off value of the bleb width-to-height ratio level for predicting bleb absorption at 6 months was 7, with 89% sensitivity and 83% specificity. CONCLUSIONS: Visual improvement may occur with late resolution of residual subfoveal fluid. A bleb width-to-height ratio >7 indicates a higher risk of SRF to persist beyond 6 months after surgery. PMID- 26139049 TI - SSRI-associated optic neuropathy. AB - PURPOSE: We report five cases of optic neuropathy (ON) identified over a 2-year period within an island population of 140 000. These cases display characteristics possibly related to long-term treatment with selective serotonin reuptake inhibitors (SSRIs). METHODS: Retrospective analysis of casenotes. Each case has been assessed using the Naranjo algorithm to indicate likelihood of adverse drug reaction (ADR). RESULTS: Clinical assessment and investigation confirmed ON in all cases with a vascular origin suspected. SSRI cessation may help protect the unaffected eye and in some cases recovery of vision seems possible. The Naranjo scores indicated possible ADR in four cases and probable ADR in one case. CONCLUSIONS: In 2004, ~7% of the UK adult population was receiving SSRI treatment for a range of 4.8-7.7 years. The most common ophthalmic side effect is acute glaucoma. Currently, there remain no reports of SSRI associated ON, although papilloedema has been reported. A potential mechanism for ischaemic optic neuropathy (ION) has been described in relation to raised serotonin levels. A single case of central retinal vein occlusion exists along with reports of deep vein thrombosis (DVT) and ischaemic stroke. We recommend a review of SSRI treatment in cases of acute ON. PMID- 26139050 TI - Trabeculectomy ab interno (trabectome): yet another possibility in the treatment of uncontrolled glaucomatocyclitic crisis under systemic valganciclovir therapy? AB - PURPOSE: To assess the outcome of trabectome surgery in the treatment of glaucomatocyclitic crisis (Posner-Schlossman syndrome) in patients with uncontrolled intraocular pressure (IOP). PATIENTS/METHODS: Trabectome surgery was performed in seven patients with diagnosed glaucomatocyclitic crisis and uncontrolled IOP where cytomegalovirus DNA was verified by polymerase chain reaction in aqueous humour samples. All patients were treated with oral valganciclovir. After surgery the patients were followed-up for 12 months. RESULTS: Mean IOP before trabectome surgery was 40+/-10 mm Hg (range 33-58 mm Hg). The mean number of antiglaucoma medication prior to surgery was 3.1+/-0.4. By the end of the 12 months, IOP in all patients was reduced to normal level (13+/-1 mm Hg) and their antiglaucoma medication was decreased to 0.8+/-1.1. No recurring attack of glaucomatocyclitic crisis occurred. DISCUSSION: In addition to oral valganciclovir therapy, trabectome surgery seems to be a reliable and effective tool for the management of glaucomatocyclitic crisis with uncontrolled IOP. PMID- 26139051 TI - Electrophysiological, Electroanatomical, and Structural Remodeling of the Atria as Consequences of Sustained Obesity. AB - BACKGROUND: Obesity and atrial fibrillation (AF) are public health issues with significant consequences. OBJECTIVES: This study sought to delineate the development of global electrophysiological and structural substrate for AF in sustained obesity. METHODS: Ten sheep fed ad libitum calorie-dense diet to induce obesity over 36 weeks were maintained in this state for another 36 weeks; 10 lean sheep with carefully controlled weight served as controls. All sheep underwent electrophysiological and electroanatomic mapping; hemodynamic and imaging assessment (echocardiography and dual-energy x-ray absorptiometry); and histology and molecular evaluation. Evaluation included atrial voltage, conduction velocity (CV), and refractoriness (7 sites, 2 cycle lengths), vulnerability for AF, fatty infiltration, atrial fibrosis, and atrial transforming growth factor (TGF)-beta1 expression. RESULTS: Compared with age-matched controls, chronically obese sheep demonstrated greater total body fat (p < 0.001); LA volume (p < 0.001); LA pressure (p < 0.001), and PA pressures (p < 0.001); reduced atrial CV (LA p < 0.001) with increased conduction heterogeneity (p < 0.001); increased fractionated electrograms (p < 0.001); decreased posterior LA voltage (p < 0.001) and increased voltage heterogeneity (p < 0.001); no change in the effective refractory period (ERP) (p > 0.8) or ERP heterogeneity (p > 0.3). Obesity was associated with more episodes (p = 0.02), prolongation (p = 0.01), and greater cumulative duration (p = 0.02) of AF. Epicardial fat infiltrated the posterior LA in the obese group (p < 0.001), consistent with reduced endocardial voltage in this region. Atrial fibrosis (p = 0.03) and TGF-beta1 protein (p = 0.002) were increased in the obese group. CONCLUSIONS: Sustained obesity results in global biatrial endocardial remodeling characterized by LA enlargement, conduction abnormalities, fractionated electrograms, increased profibrotic TGF-beta1 expression, interstitial atrial fibrosis, and increased propensity for AF. Obesity was associated with reduced posterior LA endocardial voltage and infiltration of contiguous posterior LA muscle by epicardial fat, representing a unique substrate for AF. PMID- 26139052 TI - Atrial Fibrillation and Obesity: Not Just a Coincidence. PMID- 26139053 TI - Late Restenosis After Paclitaxel-Coated Balloon Angioplasty Occurs in Patients With Drug-Eluting Stent Restenosis. AB - BACKGROUND: There are currently inadequate data on whether "late restenosis" occurs after paclitaxel-coated balloon (PCB) angioplasty for in-stent restenosis (ISR) lesions. OBJECTIVES: To evaluate the long-term safety and efficacy of PCB angioplasty, we investigated serial clinical and angiographic outcomes after PCB angioplasty for ISR lesions. METHODS: Between September 2008 and December 2012, PCB angioplasty was performed in 468 patients with 550 ISR lesions (bare-metal stent restenosis [BMS-ISR]: 114 lesions, drug-eluting stent restenosis [DES-ISR]: 436 lesions). Two serial angiographic follow-ups were routinely planned for the patients (at 6 and 18 months after the procedure). RESULTS: Early follow-up (6 months) angiography was performed for 488 lesions (89%), and recurrent restenosis occurred in 13 lesions (13.0%) in the BMS-ISR group and in 82 lesions (21.1%) in the DES-ISR group. Target lesion revascularization was performed for 7 lesions (7.0%) in the BMS-ISR group and 54 lesions (13.9%) in the DES-ISR group. Late follow-up (18 months) angiography was performed for 377 (88%) of the remaining 427 lesions (excluding target lesion revascularization lesions), and late restenosis was found in 2 lesions (2.5%) in the BMS-ISR group and 50 lesions (16.8%) in the DES-ISR group. Delayed late lumen loss was significantly larger in the DES-ISR group. Previous stent size <=2.5 mm, percentage diameter stenosis after the procedure, and in-stent occlusion lesion were independent predictors of early restenosis. DES-ISR, percentage diameter stenosis at early follow-up, and hemodialysis were independent predictors of late restenosis. CONCLUSIONS: Late restenosis occurs after PCB angioplasty for DES-ISR lesions. PMID- 26139055 TI - Is a Drug-Eluting Stent the Default Treatment Strategy for Drug-Eluting Stent Restenosis? PMID- 26139054 TI - A Prospective Randomized Trial of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis of Drug-Eluting Stents: The RIBS IV Randomized Clinical Trial. AB - BACKGROUND: Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) remains a major challenge. OBJECTIVES: This study evaluated the comparative efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients presenting with DES-ISR. METHODS: The study design of this multicenter randomized clinical trial assumed superiority of EES for the primary endpoint, in-segment minimal lumen diameter at the 6- to 9-month angiographic follow-up. RESULTS: A total of 309 patients with DES-ISR from 23 Spanish university hospitals were randomly allocated to DEB (n = 154) or EES (n = 155). At late angiography (median 247 days; 90% of eligible patients), patients in the EES arm had a significantly larger minimal lumen diameter (2.03 +/- 0.7 mm vs. 1.80 +/- 0.6 mm; p < 0.01) (absolute mean difference: 0.23 mm; 95% CI: 0.07 to 0.38) [corrected], net lumen gain (1.28 +/- 0.7 mm vs. 1.01 +/- 0.7 mm; p < 0.01), and lower percent diameter stenosis (23 +/- 22% vs. 30 +/- 22%; p < 0.01) and binary restenosis rate (11% vs. 19%; p = 0.06), compared with patients in the DEB arm. Consistent results were observed in the in-lesion analysis. At the 1 year clinical follow-up (100% of patients), the main clinical outcome measure (composite of cardiac death, myocardial infarction, and target vessel revascularization) was significantly reduced in the EES arm (10% vs. 18%; p = 0.04; hazard ratio: 0.58; 95% CI: 0.35 to 0.98), mainly driven by a lower need for target vessel revascularization (8% vs. 16%; p = 0.035). CONCLUSIONS: In patients with DES-ISR, EES provided superior long-term clinical and angiographic results compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug Eluting Balloon vs Everolimus-Eluting Stent [RIBS IV]; NCT01239940). PMID- 26139056 TI - Variation in Use of Pediatric Cardiology Subspecialty Care: A Total Population Study in California, 1983 to 2011. AB - BACKGROUND: American Academy of Pediatrics guidelines emphasize regionalized systems of care for pediatric chronic illness. There remains a paucity of information on the status of regionalized systems of care for pediatric congenital heart disease (CHD). OBJECTIVES: This study evaluated variations in use of pediatric cardiology specialty care centers (PCSCC) for pediatric patients with CHD in California between 1983 and 2011. METHODS: We performed a retrospective, total population analysis of pediatric CHD patients using the California Office of Statewide Health Planning and Development unmasked database. PCSCCs were identified by California's Title V program. RESULTS: There were 164,310 discharges meeting inclusion criterion. Discharges from PCSCCs grew from 58% to 88% between 1983 and 2011. Regionalized care was highest for surgical (96%) versus nonsurgical (71%) admissions. Admissions with a public payer increased from 42% (1983) to 61% (2011). Total bed days nearly doubled, and median length of stay increased from 2 to 3 days (nonspecialty care) and from 4 to 5 days (specialty care). There was a decrease in the pediatric CHD in-hospital death rate from 5.1 to 2.3 per 100,000 between 1983 and 2011, and a shift toward a larger percent of deaths occurring in the newborn period. CONCLUSIONS: California's inpatient regionalized specialty care of pediatric CHD has increased substantially since 1983, especially for surgical CHD discharges. The death rate has decreased, the number of bed days has increased, and a large proportion of these discharges now have public payers. Health care reform efforts must consider these shifts while protecting advances in regionalization of pediatric CHD care. PMID- 26139057 TI - Increased Survival of Congenital Heart Disease: How Did We Get Here and Now What? PMID- 26139058 TI - Atrial Fibrillation Activates AMP-Dependent Protein Kinase and its Regulation of Cellular Calcium Handling: Potential Role in Metabolic Adaptation and Prevention of Progression. AB - BACKGROUND: Atrial fibrillation (AF) is associated with metabolic stress, which activates adenosine monophosphate-regulated protein kinase (AMPK). OBJECTIVES: This study sought to examine AMPK response to AF and associated metabolic stress, along with consequences for atrial cardiomyocyte Ca(2+) handling. METHODS: Calcium ion (Ca(2+)) transients (CaTs) and cell shortening (CS) were measured in dog and human atrial cardiomyocytes. AMPK phosphorylation and AMPK association with Ca(2+)-handling proteins were evaluated by immunoblotting and immunoprecipitation. RESULTS: CaT amplitude and CS decreased at 4-min glycolysis inhibition (GI) but returned to baseline at 8 min, suggesting cellular adaptation to metabolic stress, potentially due to AMPK activation. GI increased AMPK activating phosphorylation, and an AMPK inhibitor, compound C (CompC), abolished the adaptation of CaT and CS to GI. The AMPK activator 5-aminoimidazole-4 carboxamide ribonucleotide (AICAR) increased CaT amplitude and CS, restoring CompC-induced CaT and CS decreases. CompC decreased L-type calcium channel current (ICa,L), along with ICa,L-triggered CaT amplitude and sarcoplasmic reticulum (SR) Ca(2+) content under voltage clamp conditions in dog cells and suppressed CaT and ICa,L in human cardiomyocytes. Small interfering ribonucleic acid-based AMPK knockdown decreased CaT amplitude in neonatal rat cardiomyocytes. L-type Ca(2+) channel alpha subunits coimmunoprecipitated with AMPKalpha. Atrial AMPK-activating phosphorylation was enhanced by 1 week of electrically maintained AF in dogs; fractional AMPK phosphorylation was increased in paroxysmal AF and reduced in longstanding persistent AF patients. CONCLUSIONS: AMPK is activated by metabolic stress and AF, and helps maintain the intactness of atrial ICa,L, Ca(2+) handling, and cell contractility. AMPK contributes to the atrial compensatory response to AF-related metabolic stress; AF-related metabolic responses may be an interesting new therapeutic target. PMID- 26139059 TI - AMPK and the Atrial Response to Metabolic Inhibition. PMID- 26139060 TI - Cardiac Arrest: A Treatment Algorithm for Emergent Invasive Cardiac Procedures in the Resuscitated Comatose Patient. AB - Patients who are comatose after cardiac arrest continue to be a challenge, with high mortality. Although there is an American College of Cardiology Foundation/American Heart Association Class I recommendation for performing immediate angiography and percutaneous coronary intervention (when indicated) in patients with ST-segment elevation myocardial infarction, no guidelines exist for patients without ST-segment elevation. Early introduction of mild therapeutic hypothermia is an established treatment goal. However, there are no established guidelines for risk stratification of patients for cardiac catheterization and possible percutaneous coronary intervention, particularly in patients who have unfavorable clinical features in whom procedures may be futile and affect public reporting of mortality. An algorithm is presented to improve the risk stratification of these severely ill patients with an emphasis on consultation and evaluation of patients prior to activation of the cardiac catheterization laboratory. PMID- 26139061 TI - The Multifaceted Clinical Readouts of Platelet Inhibition by Low-Dose Aspirin. AB - Inactivation of platelet cyclooxygenase (COX)-1 by low-dose aspirin leads to long lasting suppression of thromboxane (TX) A2 production and TXA2-mediated platelet activation and aggregation. This effect is necessary and sufficient to explain aspirin's unique (among other COX-1 inhibitors) effectiveness in preventing atherothrombosis, as well as its shared (with other antiplatelet agents) bleeding liability. However, different mechanisms of action have been suggested to explain other beneficial effects of aspirin, such as prevention of venous thromboembolism, chemoprevention of colorectal (and other) cancers, and reduced risk of dementia. These mechanisms include acetylation of other proteins in blood coagulation, inhibition of COX-2 activity, and other COX-independent mechanisms. The intent of this review is to develop the concept that the multifaceted therapeutic effects of low-dose aspirin may reflect pleiotropic consequences of platelet inhibition on pathophysiological tissue repair processes. Furthermore, the clinical implications of this concept will be discussed in terms of current clinical practice and future research. PMID- 26139062 TI - Simplicity and Insightfulness: A Promise and its Results: JACC at 1 Year. PMID- 26139063 TI - Fellows-in-Training & Early Career Page--The First Anniversary: A Vision, a Motivation, an Opportunity. PMID- 26139064 TI - Percutaneous Mitral Valve Repair for Acute Mitral Regurgitation After an Acute Myocardial Infarction. PMID- 26139065 TI - Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis Patients Undergoing Chronic Dialysis. PMID- 26139066 TI - Trimethylamine-N-Oxide and Heart Failure. PMID- 26139067 TI - Reply: Trimethylamine-N-Oxide and Heart Failure. PMID- 26139068 TI - Mode of Death Prevention by Serelaxin. PMID- 26139069 TI - Reply: Mode of Death Prevention by Serelaxin. PMID- 26139070 TI - Defensive medicine: implications for clinical practice, patients and healthcare policy. PMID- 26139071 TI - Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors: An Investigation of Design Flexibility. AB - The design flexibility that polymeric micelles offer in the fabrication of optical nanosensors for ratiometric pH measurements is investigated. pH nanosensors based on polymeric micelles are synthesized either by a mixed micellization approach or by a postmicelle modification strategy. In the mixed micellization approach, self-assembly of functionalized unimers followed by shell cross-linking by copper-catalyzed azide-alkyne cycloaddition (CuAAC) results in stabilized cRGD-functionalized micelle pH nanosensors. In the postmicelle modification strategy, simultaneous cross-linking and fluorophore conjugation at the micelle shell using CuAAC results in a stabilized micelle pH nanosensor. Compared to the postmicelle modification strategy, the mixed-micellization approach increases the control of the overall composition of the nanosensors. Both approaches provide stable nanosensors with similar pKa profiles and thereby nanosensors with similar pH sensitivity. PMID- 26139072 TI - Validation of a liquid chromatography-triple quadrupole mass spectrometric method for the determination of 5-nitro-5'-hydroxy-indirubin-3'-oxime (AGM-130) in human plasma and its application to microdose clinical trial. AB - A liquid chromatography-triple quadrupole mass spectrometric (LC-MS/MS) method was developed and validated for the determination of 5-nitro-5'-hydroxy-indirubin 3'-oxime (AGM-130) in human plasma to support a microdose clinical trial. The method consisted of a liquid-liquid extraction for sample preparation and LC MS/MS analysis in the positive ion mode using TurboIonSpray(TM) for analysis. d3 AGM-130 was used as the internal standard. A linear regression (weighted 1/concentration) was used to fit calibration curves over the concentration range of 10-2000 pg/mL for AGM-130. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 96.6% with a precision (coefficient of variation, CV) of 4.4%. For quality control samples at 30, 160 and 1600 pg/mL, the between run CV was <=5.0 %. Between-run accuracy ranged from 98.1 to 101.0%. AGM-130 was stable in 50% acetonitrile for 168 h at 4 degrees C and 6 h at room temperature. AGM-130 was also stable in human plasma at room temperature for 6 h and through three freeze thaw cycles. The variability of selected samples for the incurred sample reanalysis was <=12.7% when compared with the original sample concentrations. This validated LC-MS/MS method for determination of AGM-130 was used to support a phase 0 microdose clinical trial. PMID- 26139073 TI - Peritoneal cytology as prognostic factor in cervical cancer. AB - BACKGROUND: To investigate the prognostic role of peritoneal cytology (PC) in cervical cancer patients undergoing radical hysterectomy. METHODS: We retrospectively analyzed 120 stage IA1-IIIB patients with cervical cancer who underwent peritoneal fluid collection for cytology during radical hysterectomy. Neoadjuvant chemotherapy and/or radiotherapy was performed in 48% of the cases. All PC specimens were obtained by aspiration of free-fluid when present or by peritoneal washing. The relationships between cytological diagnosis, histological variables, and prognosis were investigated. RESULTS: PC was positive in 4 out of 120 (3.3%) cases. All were advanced stage adenocarcinomas. Overall, 4 out of 26 (15.3%) cases with adenocarcinoma were positive, and all presented with free fluid in the pelvis. No positive PC was found among squamous cancers. Histological subtype (P: 0.002) and parametrial (P < 0.001) and vaginal (P: 0.002) involvement presented a statistically significant correlation with PC positivity. The prognostic analysis of histological parameters demonstrated that parametrial (P: 0.007), vaginal (P: 0.04), and lymph node involvements (P: 0.003) were significantly correlated with a shorter disease-free survival. CONCLUSIONS: The series indicates that PC in squamous cell cervical cancer is not a significant prognostic factor. Its routine collection in squamous cancer should be abandoned in this setting. On the other hand, the unfavorable prognostic profile of PC positive cases in our investigation suggest a possible impact of this variable on outcome. The significant link between PC and locally advanced adenocarcinomas underwent neoadjuvant therapy before surgery warrants a further investigation to assess its real prognostic value and its indication in this particular clinical setting. PMID- 26139074 TI - Comment on "The Mechanism of Pyrolysis of Benzyl Azide: Spectroscopic Evidence for Benzenemethanimine Formation". PMID- 26139075 TI - In silico ligand binding studies of cyanogenic beta-glucosidase, dhurrinase-2 from Sorghum bicolor. AB - Dhurrinase, a cyanogenic beta-glucosidase from Sorghum bicolor is the key enzyme responsible for the hydrolysis of dhurrin to produce toxic hydrogen cyanide, as a part of plant defence mechanism. Dhurrinase 1 (SbDhr1) and dhurrinase 2 (SbDhr2), two isozymes have been isolated and characterized from S. bicolor. However, there is no information in the literature about the three dimensional (3D) structure of SbDhr2 and molecular interactions involved between the protein and ligand. In this study, the three dimensional structure of SbDhr2 was built based on homology modeling by using the X-ray crystallographic structure of its close homologue SbDhr1 as the template. The generated 3D model was energy minimized and the quality was validated by Ramachndran plot, various bioinformatic tools and their relevant parameters. Stability, folding-unfolding and flexibility of the modeled SbDhr2 was evaluated on the basis of RMSD, radius of gyration (Rg) and RMSF values respectively, obtained through molecular dynamic (MD) simulation. Further, molecular docking was performed with its natural substrate dhurrin, one substrate analogue, three un-natural substrates, and one inhibitor. Analysis of molecular interactions in the SbDhr2-ligand complexes revealed the key amino acid residues responsible to stabilize the ligands within the binding pocket through non-bonded interactions and some of them were found to be conserved (Glu239, Tyr381, Trp426, Glu454, Trp511). Reasonably broader substrate specificity of SbDhr2 was explained through the wider entrance passage observed in comparison to SbDhr1. PMID- 26139076 TI - The Earlier, the Worse? Age of Onset of Sexual Interest in Children. AB - AIM: Investigating the variability of the age of onset (AOO) of sexual interest in children (SIC) and the interrelations of important measures in individuals having a SIC, especially the role of the AOO. METHODS: A sample of 75 individuals from different contexts having a SIC was examined within an online survey. We explored the relations between AOO and other characteristics of the sample using correlation coefficients. The main outcome measures were self-reported AOO of the SIC, its exclusiveness, its flexibility over time, participants' motivation to change it, and their self-efficacy for modifying it. RESULTS: Results displayed that the AOO ranges from 6 to 44, and has a mean value of 17 and a median of 15 years. AOO correlates only with the flexibility, indicating that the earlier participants recognized their SIC, the less change they have experienced over time. CONCLUSION: AOO of SIC may be broadly distributed and related to its flexibility. Further studies should clarify the relevance of these preliminary results and their possible implications for clinical practice. PMID- 26139077 TI - Could transient hypoxia be associated with rhythmic masticatory muscle activity in sleep bruxism in the absence of sleep-disordered breathing? A preliminary report. AB - Sleep bruxism (SB) is a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth during sleep. Sleep bruxism activity is characterised by rhythmic masticatory muscle activity (RMMA). Many but not all RMMA episodes are associated with sleep arousal. The aim of this study was to evaluate whether transient oxygen saturation level change can be temporally associated with genesis of RMMA/SB. Sleep laboratory or home recordings data from 22 SB (tooth grinding history in the absence of reported sleep-disordered breathing) and healthy subjects were analysed. A total of 143 RMMA/SB episodes were classified in four categories: (i) no arousal + no body movement; (ii) arousal + no body movement; (iii) no arousal + body movement; (iv) arousal + body movement. Blood oxygen levels (SaO2 ) were assessed from finger oximetry signal at the baseline (before RMMA), and during RMMA. Significant variation in SaO2 over time (P = 0.001) was found after RMMA onset (+7 to +9 s). No difference between categories (P = 0.91) and no interaction between categories and SaO2 variation over time (P = 0.10) were observed. SaO2 of six of 22 subjects (27%) remained equal or slight increase after the RMMA/SB onset (+8 s) compared to baseline; 10 subjects (45%) slightly decreased (drop 0.01-1%) and the remaining (27%) decreased between 1% and 2%. These preliminary findings suggest that a subgroup of SB subjects had (i) a minor transient hypoxia potentially associated with the onset of RMMA episodes, and this (ii) independently of concomitant sleep arousal or body movements. PMID- 26139078 TI - Can body mass index predict survival outcomes in patients treated with radical nephroureterectomy for upper-tract urothelial carcinoma? AB - PURPOSE: To assess the relationship between body mass index (BMI) and survival outcomes in Korean patients with upper-tract urothelial carcinoma (UTUC). METHODS: A single-institutional retrospective analysis was conducted using clinical and pathological data of 445 UTUC patients who had undergone radical nephroureterectomy with bladder cuff excision from 1997 to 2012. Enrolled patients were classified into normal weight (BMI < 23 kg/m(2)), overweight (BMI 23-24.9 kg/m(2)), and obese (BMI >= 25 kg/m(2)) in accordance with BMI cutoffs for Asian populations. The impact of BMI on intravesical recurrence (IVR)-free survival, overall survival (OS), and cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis with the log-rank test and the Cox proportional hazard model. RESULTS: The median BMI of all patients was 24.2 kg/m(2) (interquartile range 22.2-25.8). There were no significant differences in the IVR free survival rates according to BMI classification (p = 0.488). The 5-year OS and CSS rates were 58.8, 66.3, and 76.3 % (p = 0.057) and 67.4, 69.3, and 81.5 % (p = 0.021) in the normal, overweight, and obese groups, respectively. In the univariate analysis, obesity (BMI >= 25 kg/m(2)) was a significant predictor of better OS [hazard ratio (HR) 0.63; 95 % confidence interval (CI) 0.43-0.92, p = 0.017] and CSS (HR 0.53; 95 % CI 0.33-0.84, p = 0.007) than normal weight. However, these associations could not be confirmed in the multivariable analysis after adjusting for other clinicopathological factors, such as tumor stage, tumor grade, lymphovascular invasion, and surgical margin. CONCLUSIONS: Our study results are inconclusive, in that, the multivariate analysis did not identify the influence of BMI on survival, although higher BMI appears clinically associated with favorable survival outcomes in Korean patients with UTUC. PMID- 26139079 TI - Cytopathologic features of epithelioid inflammatory myofibroblastic sarcoma with correlation of histopathology, immunohistochemistry, and molecular cytogenetic analysis. AB - BACKGROUND: Epithelioid inflammatory myofibroblastic sarcoma (E-IMS) is a recently established rare variant of inflammatory myofibroblastic tumor. It is characterized by a distinctive constellation of clinical, pathological, and molecular features, including a nearly exclusive intraabdominal location, strong male predilection, aggressive clinical course, predominance of epithelioid tumor cells, and Ran-binding protein 2 (RANBP2)-anaplastic lymphoma kinase (ALK) fusion in the majority of cases. To the authors' knowledge, the cytologic features of E IMS have not been described to date. METHODS: Cases of E-IMS that had corresponding cytology were searched. Six cytology samples (1 fine-needle aspiration sample, 2 imprint samples, and 3 effusion fluids) containing tumor cells were identified in 5 patients with E-IMS. RESULTS: The cytomorphology included large monotonous epithelioid cells arranged in loose aggregates or singly, with admixed myxoid stroma, and an inflammatory background rich in neutrophils. The tumor cells had a large, round, eccentric nucleus with vesicular chromatin, prominent nucleoli, and moderate amounts of pale cytoplasm. Delicate thin-walled branching vessels traversing tumor aggregates was a prominent feature in a fine-needle aspiration sample. Immunohistochemically, ALK was positive in all 5 tumors, with a nuclear membranous staining pattern noted in 3 cases and a cytoplasmic pattern observed in the other 2 cases. ALK rearrangement was confirmed in all 5 tumors by molecular genetic studies. CONCLUSIONS: The cytologic features of E-IMS recapitulate its histologic characteristics. E-IMS merits inclusion in the differential diagnosis of any intraabdominal, large epithelioid cell neoplasm. Confirmation of ALK rearrangement is advisable because patients may benefit from targeted therapies. PMID- 26139080 TI - The role of GRIK4 gene in treatment-resistant depression. AB - Several lines of evidence implicate abnormalities in glutamatergic neural transmission in major depressive disorder (MDD) and treatment response. A high percentage of MDD patients do not respond adequately to antidepressants and are classified as having treatment-resistant depression (TRD). In this study we investigated five GRIK4 variants, previously associated with antidepressants response, in an Italian cohort of 247 MDD no-TRD and 380 TRD patients. We found an association between rs11218030 G allele and TRD. Moreover, significant associations between rs11218030 and rs1954787 and the presence of psychotic symptoms were observed. In conclusion, our data support the involvement of GRIK4 in TRD and in the risk of developing psychotic symptoms during depressive episodes. PMID- 26139081 TI - Revealing local variations in nanoparticle size distributions in supported catalysts: a generic TEM specimen preparation method. AB - The specimen preparation method is crucial for how much information can be gained from transmission electron microscopy (TEM) studies of supported nanoparticle catalysts. The aim of this work is to develop a method that allows for observation of size and location of nanoparticles deposited on a porous oxide support material. A bimetallic Pt-Pd/Al(2)O(3) catalyst in powder form was embedded in acrylic resin and lift-out specimens were extracted using combined focused ion beam/scanning electron microscopy (FIB/SEM). These specimens allow for a cross-section view across individual oxide support particles, including the unaltered near surface region of these particles. A site-dependent size distribution of Pt-Pd nanoparticles was revealed along the radial direction of the support particles by scanning transmission electron microscopy (STEM) imaging. The developed specimen preparation method enables obtaining information about the spatial distribution of nanoparticles in complex support structures which commonly is a challenge in heterogeneous catalysis. PMID- 26139082 TI - Real-time monitoring of small biological molecules by ligation-mediated polymerase chain reaction. AB - We develop a ligation-mediated polymerase chain reaction (PCR) for real-time detection of small biological molecules in a high-throughput format. This method is extremely sensitive with a detection limit of as low as 18.8 fM for ATP and 17.3 fM for NAD(+), and it can discriminate target molecules from their analogues as well. PMID- 26139083 TI - Financing the response to HIV among gay men and other men who have sex with men: Case studies from eight diverse countries. AB - Despite reductions in the number of new HIV infections globally, the HIV epidemic among men who have sex with men (MSM) is expanding. This study characterises financing of HIV programmes for MSM and the impact of criminalisation on levels of funding, using data from five countries that criminalise same-sex sexual practices (Ethiopia, Mozambique, Guyana, India and Nigeria) and three that do not (China, Ukraine and Vietnam). For each country, all publicly available documents from the Global Fund to Fight AIDS, Tuberculosis and Malaria for approved HIV/AIDS grants in Rounds 5-9 and Country Operational Plans detailing investments made through the President's Emergency Plan for AIDS Relief (PEPFAR) from US fiscal year (FY) 2007-2009 were examined. Eleven of 20 HIV proposals to the Global Fund contained programmes for MSM totalling approximately $40 million or 6% of proposed budgets. In six countries providing activity-level data on MSM programming, PEPFAR funding that served this population and others ranged from $23.3 million in FY2007 to $35.4 million in FY2009, representing 0.5-25.9% of overall, non-treatment funding over this period. Countries that criminalise same sex sexual practices spend fewer resources on HIV programmes serving MSM. However, they also show consistent underfunding of programmes serving MSM regardless of context or geography. PMID- 26139084 TI - Characteristics of Stenotrophomonas maltophilia bacteremia in children. AB - BACKGROUND: Empiric antimicrobial coverage in compromised hosts commonly includes pseudomonal coverage but often lacks coverage against Stenotrophomonas maltophilia. Identification of risk factors specific for S. maltophilia infection may lead to prompt initiation of appropriate antibiotics and improved outcome. METHODS: We conducted a retrospective analysis of pediatric patients with bacteremia due to S. maltophilia or Pseudomonas aeruginosa from April 2002 to July 2014 at a tertiary children's hospital. Patient demographics, underlying disease, clinical course, and treatment were compared between S. maltophilia and P. aeruginosa cases. RESULTS: Nineteen children with S. maltophilia bacteremia and 49 children with P. aeruginosa bacteremia were identified. On multivariate logistic regression analysis, use of carbapenems within 7 days prior to onset (OR, 5.00; 95%CI: 1.25-20.07; P = 0.02) and previous intensive care unit stay (OR, 3.75; 95%CI: 1.13-12.47; P = 0.03) were significantly associated with S. maltophilia bacteremia compared with P. aeruginosa bacteremia. The majority of the S. maltophilia bacteremia patients had central line-associated bloodstream infection (79%), compared with the P. aeruginosa bacteremia patients (37%, P = 0.002). There were nine children (47%) who had polymicrobial infection in the S. maltophilia bacteremia group, in contrast to four (8%) in the P. aeruginosa bacteremia group (OR, 10.13; 95%CI: 2.59-39.56; P = 0.001). Consultation with an infectious diseases physician was associated with a lower rate of persistent S. maltophilia bacteremia (P = 0.04). CONCLUSIONS: Stenotrophomonas maltophilia should be considered in breakthrough bacteremia in pediatric patients who receive carbapenems within 7 days prior to onset. PMID- 26139085 TI - Treating pulmonary embolism in Pacific Asia with direct oral anticoagulants. AB - Pulmonary embolism (PE) is the principal preventable cause of in-hospital deaths. Prevalence of PE in Asians is uncertain but undoubtedly underestimated. Asians and Caucasians have similar non-genetic risk factors for PE, and there is mounting evidence that PE affects Asians much more commonly than previously supposed; incidence, especially among high-risk patients, may approach that in Caucasians. Furthermore, PE incidence in Asia is increasing, due to both increased ascertainment, and also population ageing and growing numbers of patients with predisposing risk factors. Despite being warranted, thromboprophylaxis for high-risk patients is not routine in Pacific Asian countries/regions. There also appears to be scope to implement venous thromboembolism (VTE) management guidelines more assiduously. Anticoagulants, primarily heparins and warfarin, have been the mainstays of VTE management for years; however, these agents have limitations that complicate routine use. The complexity of current guidelines has been another barrier to applying evidence based recommendations in everyday practice. Updated management approaches have considerable potential to improve outcomes. New oral anticoagulants that are easier to administer, require no, or much less, monitoring or dose-adjustment and have a favourable risk/benefit profile compared with conventional modalities, may offer an alternative with the potential to simplify VTE management. However, more information is required on practical management and the occurrence and treatment of bleeding complications. Increasing recognition of the burden of PE and new therapeutic modalities are altering the VTE management landscape in Pacific Asia. Consequently, there is a need to further raise awareness and bridge gaps between the latest evidence and clinical practice. PMID- 26139086 TI - Predictive value of markers of inflammation in the postthrombotic syndrome: a systematic review: inflammatory biomarkers and PTS. AB - BACKGROUND: The postthrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT). Inflammation may contribute to its pathophysiology. OBJECTIVES: We conducted a systematic review of studies that analyzed the association between biomarkers of inflammation and PTS in DVT patients. METHODS: The electronic databases PubMed, EMBASE, Medline, Scopus and Web of Science were searched for studies published until March 2015 that measured blood inflammation biomarker levels in adult DVT patients and reported their association with PTS development. Two reviewers independently performed full text assessment and data extraction. RESULTS: Ten studies were included. Nine reported on the association between C-reactive protein and PTS; Interleukin (IL)-6 was measured in six studies; IL-8 in four studies; Intracellular adhesion molecule (ICAM)-1 in three studies; IL-10 and vascular cell adhesion molecule-1 in two studies; and monocyte chemotactic protein-1, matrix metalloprotease-9, P-Selectin, tumor necrosis factor alpha and erythrocyte sedimentation rate were measured in one study. Studies differed in terms of populations included, exclusion criteria, methods used for biomarker measurement and statistical measures of association between biomarkers and PTS. We were able to metaanalyze results only for IL-6 and found no significant association. Descriptively, ICAM-1 was significantly associated with PTS in two out of three studies that measured it. Other biomarkers did not demonstrate a significant association with PTS. CONCLUSIONS: Our systematic review found conflicting results regarding the role of inflammatory biomarkers as predictors of PTS. ICAM -1 appears to be a promising marker for further investigation. PMID- 26139087 TI - ADAMTS13 gene variants and function in women with preeclampsia: a population- based nested case- control study from the HUNT Study. AB - INTRODUCTION: Known genetic variants with reference to preeclampsia only explain a proportion of the heritable contribution to the development of this condition. The association between preeclampsia and the risk of cardiovascular disease later in life has encouraged the study of genetic variants important in thrombosis and vascular inflammation also in relation to preeclampsia. The von Willebrand factor cleaving protease, ADAMTS13, plays an important role in micro vascular thrombosis, and partial deficiencies of this enzyme have been observed in association with cardiovascular disease and preeclampsia. However, it remains unknown whether decreased ADAMTS13 levels represent a cause or an effect of the event in placental and cardiovascular disease. METHODS: We studied the distribution of three functional genetic variants of ADAMTS13, c.1852C>G (rs28647808), c.4143_4144dupA (rs387906343), and c.3178C>T (rs142572218) in women with preeclampsia and their controls in a nested case-control study from the second Nord-Trondelag Health Study (HUNT2). We also studied the association between ADAMTS13 activity and preeclampsia, in serum samples procured unrelated in time of the preeclamptic pregnancy. RESULTS: No differences were observed in genotype, allele or haplotype frequencies of the different ADAMTS13 variants when comparing cases and controls, and no association to preeclampsia was found with lower levels of ADAMTS13 activity. CONCLUSION: Our findings indicate that ADAMTS13 variants and ADAMTS13 activity do not contribute to an increased risk of preeclampsia in the general population. PMID- 26139088 TI - Could perioperative bleeding complications be predicted using a platelet aggregation test? PMID- 26139089 TI - Increased liver enzyme levels during azathioprine treatment: beware of concomitant use of proton pump inhibitors. PMID- 26139091 TI - Cochrane reviews evidence on surgery for stress incontinence after controversy in Scotland. PMID- 26139090 TI - Colour expectations during object perception are associated with early and late modulations of electrophysiological activity. AB - It is well known that visual expectation and attention modulate object perception. Yet, the mechanisms underlying these top-down influences are not completely understood. Event-related potentials (ERPs) indicate late contributions of expectations to object processing around the P2 or N2. This is true independent of whether people expect objects (vs. no objects) or specific shapes, hence when expectations pertain to complex visual features. However, object perception can also benefit from expecting colour information, which can facilitate figure/ground segregation. Studies on attention to colour show attention-sensitive modulations of the P1, but are limited to simple transient detection paradigms. The aim of the current study was to examine whether expecting simple features (colour information) during challenging object perception tasks produce early or late ERP modulations. We told participants to expect an object defined by predominantly black or white lines that were embedded in random arrays of distractor lines and then asked them to report the object's shape. Performance was better when colour expectations were met. ERPs revealed early and late phases of modulation. An early modulation at the P1/N1 transition arguably reflected earlier stages of object processing. Later modulations, at the P3, could be consistent with decisional processes. These results provide novel insights into feature-specific contributions of visual expectations to object perception. PMID- 26139092 TI - Racial Health Disparities: A Call to Action. PMID- 26139093 TI - Aerobic exercise reduces biomarkers related to cardiovascular risk among cleaners: effects of a worksite intervention RCT. AB - PURPOSE: Blue-collar workers have an increased risk of cardiovascular disease. Accordingly, elevated levels of biomarkers related to risk of cardiovascular disease, such as high-sensitive C-reactive protein, have been observed among blue collar workers. The objective was to examine whether an aerobic exercise worksite intervention changes the level of inflammation biomarkers among cleaners. METHODS: The design was a cluster-randomized controlled trial with 4-month worksite intervention. Before the 116 cleaners aged 18-65 years were randomized, they signed an informed consent form. The reference group (n = 59) received lectures, and the aerobic exercise group (n = 57) performed worksite aerobic exercise (30 min twice a week). Levels of biomarkers (high-sensitive C-reactive protein, fibrinogen, cholesterol, low- and high-density lipoprotein cholesterol and triglyceride) were collected at baseline and after 4 months. A repeated measure, multi-adjusted, mixed-model intention-to-treat analysis was applied to compare between-group differences. The study was registered as ISRCTN86682076. RESULTS: Significant (p < 0.05) between-group reductions from baseline to follow up were found for high-sensitive C-reactive protein (-0.54 +/- 0.20 ug/ml; 95% CI -0.94, -0.14), low-density lipoprotein cholesterol (-0.32 +/- 0.11 mmol/L; 95% CI -0.54, -0.10) and the ratios of LDL/HDL (-0.30 +/- 0.08; 95% CI -0.46, -0.14), and LDL/TC cholesterol (-0.04 +/- 0.02; 95% CI -0.07, -0.01). CONCLUSION: This study indicates that an aerobic exercise intervention among cleaners leads to reduced levels of high-sensitive C-reactive protein and low-density lipoprotein cholesterol, and an unaltered level of fibrinogen. The aerobic exercise seems to improve inflammatory levels and lipoprotein profile among cleaners, with no signs of cardiovascular overload. PMID- 26139094 TI - Practical on-site measurement of heat strain with the use of a perceptual strain index. AB - OBJECTIVES: There have been increased interests in research on quantifying heat strain of construction workers and formulating corresponding guidelines for working in hot weather. The aim of this study was to validate a subjective measurement tool, the perceptual strain index (PeSI), for measuring heat strain in real-work settings. METHODS: A total of sixteen construction workers were invited to participate in the field surveys. Empiric-based human monitoring was carried out with simultaneous micrometeorological (wet-bulb globe temperature, WBGT), physiological (heart rate, HR), and perceptual (perceived exertion, RPE; thermal sensation, TS) measurements throughout the test. The relative heart rate (RHR), the physiological strain index (PSIHR), and the PeSI were then calculated accordingly. RESULTS: The PeSI exhibited moderate correlations with WBGT and RHR (r = 0.42 and 0.40, respectively), which indicated the PeSI was sensitive to the variants of WBGT and RHR. The results of regression analysis indicated that the PeSI changed in the same general manner as the PSIHR, with a relatively large determination coefficient (R(2) = 0.67). The established perceptual strain zone illustrated that the PeSI ranging from 7 to 8 would be the exposure limit of construction workers in hot weather. CONCLUSION: The PeSI is a simple, robust, reliable, and user-friendly tool for heat strain assessment in occupational settings. The perceptual strain zone will provide practical guidelines for on site heat strain monitoring for construction workers. PMID- 26139095 TI - Feasibility and Acceptability of Cryptococcal Antigen Screening and Prevalence of Cryptocococcemia in Patients Attending a Resource-Limited HIV/AIDS Clinic in Malawi. AB - BACKGROUND: The World Health Organization (WHO) recommends screening patients living with AIDS to detect and treat early cryptococcal infection. METHODS: The authors evaluated a cryptococcal antigen (CrAg) screening and treatment program at an HIV/AIDS clinic in Malawi. Eligible patients were of age >18 years, had a CD4 count <100 cells/uL or WHO clinical HIV/AIDS stage III or IV. RESULTS: Of 552 patients who presented for care, 113 were eligible, and all (100%) agreed to CrAg screening. Of them, 2 (1.8%; 95% confidence interval [CI]: 0-4.2%) patients were CrAg positive. Among those with CD4 count <100 cells/uL or WHO stage IV, the CrAg prevalence was 3.5% (95% CI: 0-8.4%) and 5.0% (95% CI: 0-15%), respectively. CONCLUSION: A CrAg screening program was acceptable to new patients in a Malawian HIV/AIDS clinic. The CrAg prevalence for patients with CD4 count < 100 cells/uL and WHO stage IV was consistent with cost-effectiveness estimates. CrAg screening and treatment programs for patients living with AIDS should be expanded. PMID- 26139096 TI - Methods to Obtain a Representative Sample of Ryan White-Funded Patients for a Needs Assessment in Los Angeles County: Results from a Replicable Approach. AB - The Health Resources and Services Administration requires that jurisdictions receiving Ryan White (RW) funding justify need, set priorities, and provide allocations using evidence-based methods. Methods and results from the 2011 Los Angeles Coordinated HIV/AIDS Needs Assessment-Care (LACHNA-Care) study are presented. Individual-level weights were applied to expand the sample from 400 to 18 912 persons, consistent with the 19 915 clients in the system. Awareness, need, and utilization for medical outpatient care were high (>90%). Other services (eg, child care) had limited awareness (21%). Majority of participants reported at least 1 service gap (81%). Lack of insurance (risk ratio [RR] = 3.0, 95% confidence interval [CI]: 1.5-6.2), substance use (RR = 2.9, 95% CI: 1.3 6.4), and past lapses in medical care (RR = 2.8, 95% CI: 1.3-5.9) were associated with gaps. Within clusters, past incarceration was associated with gaps for housing (RR = 13.5, 95% CI: 3.5-52.1), transportation (RR = 3.2, 95% CI: 1.2 8.4), and case management (RR = 4.0, 95% CI: 1.3-12.2). Applied methods resulted in representative data instrumental to RW program planning efforts. PMID- 26139097 TI - Sublethal health effects in laboratory rodents from environmentally relevant exposures to oil sands contaminants. AB - Increasing activity of oil sands extraction and processing in northern Alberta is marked by ongoing controversy about the nature and extent of associated environmental impacts. Bitumen contains a mixture of toxic chemicals, including metals and residual polycyclic aromatic hydrocarbons (PAHs), whose release into the environment poses a distinct risk to the surrounding environment, plus wildlife and human health. In the present study, the authors evaluated several subclinical biomarkers of exposure and effect to mixtures of metals (Pb, Cd, and Hg) and/or PAHs (3 alkylated forms) at environmentally relevant concentrations (100-fold and 10-fold higher than the maximum dissolved concentrations found in snow, to simulate a worst-case scenario), using laboratory mice as a model for future studies of small mammals in the wild. Both metals and alkyl-PAHs exposure were associated with 1) increased relative liver, kidney, and spleen size; 2) alterations in the homeostasis of the antioxidant vitamins A and E in liver; and 3) compromised glutathione redox status in testes, with results also indicating synergistic interactions from co-exposure. The combination of morphometric and oxidative stress biomarkers provide reliable and sensitive measures of the response to contaminant exposure in a mammalian model, suggesting associated physiological costs. Based on the present experimental study, the authors propose that wild small mammals will prove to be valuable sentinel species reflecting sublethal health effects from oil sands-related contaminants. The present study's results also present a basis for the interpretation of future field data. PMID- 26139098 TI - MIF interacts with CXCR7 to promote receptor internalization, ERK1/2 and ZAP-70 signaling, and lymphocyte chemotaxis. AB - Macrophage migration-inhibitory factor (MIF) is a pleiotropic cytokine with chemokine-like functions and is a mediator in numerous inflammatory conditions. Depending on the context, MIF signals through 1 or more of its receptors cluster of differentiation (CD)74, CXC-motif chemokine receptor (CXCR)2, and CXCR4. In addition, heteromeric receptor complexes have been identified. We characterized the atypical chemokine receptor CXCR7 as a novel receptor for MIF. MIF promoted human CXCR7 internalization up to 40%, peaking at 50-400 nM and 30 min, but CXCR7 internalization by MIF was not dependent on CXCR4. Yet, by coimmunoprecipitation, fluorescence microscopy, and a proximity ligation assay, CXCR7 was found to engage in MIF receptor complexes with CXCR4 and CD74, both after ectopic overexpression and in endogenous conditions in a human B-cell line. Receptor competition binding and coimmunoprecipitation studies combined with sulfo-SBED biotin-transfer provided evidence for a direct interaction between MIF and CXCR7. Finally, we demonstrated MIF/CXCR7-mediated functional responses. Blockade of CXCR7 suppressed MIF-mediated ERK- and zeta-chain-associated protein kinase (ZAP) 70 activation (from 2.1- to 1.2-fold and from 2.5- to 1.6-fold, respectively) and fully abrogated primary murine B-cell chemotaxis triggered by MIF, but not by CXCL12. B cells from Cxcr7(-/-) mice exhibited an ablated transmigration response to MIF, indicating that CXCR7 is essential for MIF-promoted B-cell migration. Our findings provide biochemical and functional evidence that MIF is an alternative ligand of CXCR7 and suggest a functional role of the MIF-CXCR7 axis in B lymphocyte migration. PMID- 26139099 TI - Timing of cardiomyocyte growth, maturation, and attrition in perinatal sheep. AB - Studies in altricial rodents attribute dramatic changes in perinatal cardiomyocyte growth, maturation, and attrition to stimuli associated with birth. Our purpose was to determine whether birth is a critical trigger controlling perinatal cardiomyocyte growth, maturation and attrition in a precocial large mammal, sheep (Ovis aries). Hearts from 0-61 d postnatal lambs were dissected or enzymatically dissociated. Cardiomyocytes were measured by micromorphometry, cell cycle activity assessed by immunohistochemistry, and nuclear number counted after DNA staining. Integration of this new data with published fetal data from our laboratory demonstrate that a newly appreciated >30% decrease in myocyte number occurred in the last 10 d of gestation (P < 0.0005) concomitant with an increase in cleaved poly (ADP-ribose) polymerase 1 (P < 0.05), indicative of apoptosis. Bisegmental linear regressions show that most changes in myocyte growth kinetics occur before birth (median = 15.2 d; P < 0.05). Right ventricular but not left ventricular cell number increases in the neonate, by 68% between birth and 60 d postnatal (P = 0.028). We conclude that in sheep few developmental changes in cardiomyocytes result from birth, excepting the different postnatal degrees of free wall hypertrophy between the ventricles. Furthermore, myocyte number is reduced in both ventricles immediately before term, but proliferation increases myocyte number in the neonatal right ventricle. PMID- 26139100 TI - Ultrastructural Changes of Brain Tissues Surrounding Hematomas after Intracerebral Hemorrhage. AB - Our knowledge about pathophysiology of intracerebral hemorrhage (ICH) mainly originates from preclinical models of ICH. In this study, cerebral ultrastructure surrounding hematoma and its correlation with clinical severity were investigated in ICH patients. Thirty patients with basal ganglia hemorrhage and 6 control subjects were enrolled. Surgical evacuation was performed for patients with a blood loss >30 ml. Stroke severity was assessed using the Glasgow Coma Scale (GCS) and the National Institute of Health Stroke Scale (NIHSS). Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of tissue specimens. Neural cells surrounding the hematomas showed evidence of cell swelling and necrosis. Decreased numbers of organelles and mitochondrial cristae were accompanied by cytoplasmic vacuolization, nuclear membrane invagination and breakdown, and intranuclear chromatic agglutination. These changes resulted in disintegration together with malacia, disappearance of the nucleus and nucleolus, and karyopyknosis. More serious ultrastructural damage was seen in patients with greater NIHSS scores, lower GCS scores, and greater bleeding volumes (p < 0.001). These findings suggest that neural cells undergo unfavorable ultrastructural changes that are responsible for dysfunction after ICH. PMID- 26139101 TI - Cyclic Adenosine Monophosphate-Mediated Enhancement of Vascular Endothelial Growth Factor Released by Differentiated Human Monocytic Cells: The Role of Protein Kinase A. AB - OBJECTIVE: Our investigation was designed to examine the signaling pathway involved in the enhancement of vascular endothelial growth factor (VEGF) release by beta-adrenoceptor agonists. MATERIALS AND METHODS: Human U937 cells differentiated into macrophages were primed with lipopolysaccharide (LPS) in the absence or presence of beta-adrenoceptor agonists and antagonists. The VEGF released and the intracellular cyclic adenosine monophosphate (cAMP) generated were assayed by ELISA. Where necessary, differences between mean values were tested for significance using Student's t test. RESULTS: Isoprenaline, procaterol and salbutamol concentration-dependently enhanced the release of VEGF induced by LPS in U937 cells. R*,R*-(+/-)-4-[2-[(2-(3-chlorophenyl)-2 hydroxyethyl)amino]propyl]phenoxyacetic acid (BRL 37344), a selective beta3 adrenoceptor agonist, did not enhance VEGF release. Using isoprenaline as an agonist, propranolol, ICI 118551 and atenolol produced a parallel rightward shift of the concentration-response curve with no reduction in the maximum response. The -logKB values were 8.12 +/- 0.17, 8.03 +/- 0.05 and 7.23 +/- 0.05 for propranolol, ICI 118551 and atenolol, respectively, indicating the possible involvement of both beta1- and beta2-adrenoceptor subtypes. Isoprenaline and prostaglandin E2 concentration-dependently increased cAMP generation in U937 cells. Isoprenaline, db-cAMP and 6-Bnz-cAMP, a protein kinase A (PKA) activator, all enhanced VEGF release induced by LPS, and this effect was abolished by KT 5720 and Rp-cAMPS, which are both selective PKA inhibitors, suggesting that PKA is the downstream effector of cAMP activity. 8-CPT-cAMP, a selective activator of the Epac system, had no effect on VEGF release induced by LPS, indicating that the Epac pathway played no role in the release process. CONCLUSION: In this study, we established that beta1- and beta2- but not beta3-adrenoceptors mediated cAMP-dependent enhancement of VEGF release induced by LPS in differentiated U937 cells, and that PKA was the downstream effector of cAMP activity. PMID- 26139103 TI - Facile synthesis of luminescent and amorphous La2O3-ZrO2:Eu3+ nanofibrous membranes with robust softness. AB - Novel luminescent and amorphous La2O3-ZrO2:Eu(3+) (LZE) nanofibrous membranes with robust softness are fabricated for the first time via a facile electrospinning technique. By incorporating zirconium oxide, the as-prepared lanthanum oxide nanofibrous membranes can be dramatically changed from extreme fragility to robust softness. Meanwhile, the softness and luminescent performance of LZE nanofibrous membranes can be finely controlled by regulating the doping concentration of zirconium oxide and europium in lanthanum oxide nanofibers. Additionally, the crystal structure analysis using X-ray diffractometer and high resolution transmission electron microscopy measurements have confirmed the correlation between the amorphous structure and softness. Furthermore, LZE membranes show the characteristic emission of Eu(3+) corresponding to (5)D(0, 1, 2)-(7)F(0, 1, 2, 3, 4) transitions due to an efficient energy transfer from O(2-) to Eu(3+). The LZE nanofibrous membranes with the optimum doping Eu(3+) concentration of 3 mol% exhibit excellent softness and luminescent properties, which make the materials to have potential applications in fluorescent lamps and field emission displays. PMID- 26139102 TI - Transposable elements, mRNA expression level and strand-specificity of small RNAs are associated with non-additive inheritance of gene expression in hybrid plants. AB - BACKGROUND: Gene expression inheritance patterns in Arabidopsis hybrid plants were investigated for correlation with the presence of transposable elements (TEs) and small RNA profile. RESULTS: The presence of TEs in a gene and the expression of small RNA matching a gene were both found to be associated with non additive mRNA inheritance patterns in hybrids. Expression levels below mid-parent values in the hybrids were associated with low mRNA expression in parents, with the presence of small RNA from both strands, and with the presence of TEs. High parent dominance of mRNA levels was found to be associated with high parental mRNA expression levels, the absence of TEs, and for some genes, with small RNA fragments that are predominantly from the sense strand. These small RNAs exhibit a broader size distribution than siRNA and reduced nucleotide end bias, which are consistent with an origin from degraded mRNA. Thus, increased as well as decreased gene expression in hybrids relative to the parental mean is associated with gene expression levels, TE presence and small RNA fragments with differing characteristics. CONCLUSIONS: The data presented here is consistent with a role for differential mRNA decay kinetics as one mechanism contributing to high-parent dominance in gene expression. Our evidence is also consistent with trans repression by siRNA and TEs as the cause of low-parent dominance. PMID- 26139104 TI - Meta-analysis of hepatic cytochrome P450 ontogeny to underwrite the prediction of pediatric pharmacokinetics using physiologically based pharmacokinetic modeling. AB - The accurate prediction of pharmacokinetics (PK) is fundamental to underwriting safety and efficacy in pediatric clinical trials; age-dependent PK may be observed with pediatrics because of the growth and maturation processes that occur during development. Understanding the ontogeny of drug-metabolizing enzymes is a critical enabler for pediatric PK prediction, as enzyme expression or activity may change with age. Although ontogeny functions for the cytochrome P450s (CYPs) have been developed, disconnects between ontogeny functions for the same CYP may exist, depending on whether the functions were derived from in vitro or in vivo data. This report describes the development of ontogeny functions for all the major hepatic CYPs based on in vitro or in vivo data; these ontogeny functions were subsequently incorporated into a physiologically based pharmacokinetic model and evaluated. Pediatric PK predictions based on in vivo derived ontogeny functions performed markedly better than those developed from in vitro data for intravenous (100% versus 51% within 2-fold, respectively) and oral (98% versus 67%, respectively) dosing. The verified models were then applied to complex pediatric scenarios involving active metabolites, CYP polymorphisms and physiological changes because of critical illness; the models reasonably explained the observed age-dependent changes in pediatric PK. PMID- 26139105 TI - Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task. AB - OBJECTIVE: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. METHODS: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. RESULTS: Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. CONCLUSIONS: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. PMID- 26139107 TI - Adverse effects of conventional thrice-weekly hemodialysis: is it time to avoid 3 day interdialytic intervals? AB - BACKGROUND: Maintenance hemodialysis is typically scheduled thrice weekly due to simple logistic reasons; thus, the vast majority of hemodialysis patients receive renal replacement therapy for two shorter 2-day intervals and a longer 3-day interval. As compared to the 2-day interval, we review the ill effects of the longer 3-day interdialytic interval in this report. SUMMARY: Large-scale observational studies show that both cardiovascular-related hospital admissions and mortality occur more frequently on the day following the long interdialytic interval than on any other day of the week. Although the reasons for excess mortality are obscure, several pathophysiologic mechanisms may be involved, such as a greater magnitude of change during the long interdialytic interval in the following parameters: volume status, electrolyte and acid-base status, arterial wall and left ventricle mechanics. These data raise the need for re-examining the issue of timing and frequency of prescribed dialysis regimens in an attempt to improve patient outcomes. Although enhanced-frequency and/or extended-time dialysis schedules may mitigate the risks of the long interdialytic interval, the benefit of such dialytic modalities on survival is not yet proven. Key Message: This article summarizes currently available epidemiologic and pathophysiologic evidence on the adverse effects related to the long interdialytic interval of thrice-weekly hemodialysis and discusses the need to research further alternative dialysis practices that could mitigate these risks. PMID- 26139106 TI - Vemurafenib resistance reprograms melanoma cells towards glutamine dependence. AB - BACKGROUND: (V600) BRAF mutations drive approximately 50% of metastatic melanoma which can be therapeutically targeted by BRAF inhibitors (BRAFi) and, based on resistance mechanisms, the combination of BRAF and MEK inhibitors (BRAFi + MEKi). Although the combination therapy has been shown to provide superior clinical benefits, acquired resistance is still prevalent and limits the overall survival benefits. Recent work has shown that oncogenic changes can lead to alterations in tumor cell metabolism rendering cells addicted to nutrients, such as the amino acid glutamine. Here, we evaluated whether melanoma cells with acquired resistance display glutamine dependence and whether glutamine metabolism can be a potential molecular target to treat resistant cells. METHODS: Isogenic BRAFi sensitive parental (V600) BRAF mutant melanoma cell lines and resistant (derived by chronic treatment with vemurafenib) sub-lines were used to assess differences in the glutamine uptake and sensitivity to glutamine deprivation. To evaluate a broader range of resistance mechanisms, isogenic pairs where the sub-lines were resistant to BRAFi + MEKi were also studied. Since resistant cells demonstrated increased sensitivity to glutamine deficiency, we used glutaminase inhibitors BPTES [bis-2-(5 phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide] and L-L DON (6-Diazo-5-oxo-L-norleucine) to treat MAPK pathway inhibitor (MAPKi) resistant cell populations both in vitro and in vivo. RESULTS: We demonstrated that MAPKi-acquired resistant cells uptook greater amounts of glutamine and have increased sensitivity to glutamine deprivation than their MAPKi-sensitive counterparts. In addition, it was found that both BPTES and L-DON were more effective at decreasing cell survival of MAPKi-resistant sub-lines than parental cell populations in vitro. We also showed that mutant NRAS was critical for glutamine addiction in mutant NRAS driven resistance. When tested in vivo, we found that xenografts derived from resistant cells were more sensitive to BPTES or L-DON treatment than those derived from parental cells. CONCLUSION: Our study is a proof-of-concept for the potential of targeting glutamine metabolism as an alternative strategy to suppress acquired MAPKi-resistance in melanoma. PMID- 26139108 TI - Medication Assistant-Certification Program in Washington State: Barriers to implementation. AB - Medication assistants (MAs) are a legal alternative that enables licensed nurses to safely delegate medication administration to stable residents in non-acute settings. The purpose of this study was to query the beliefs and understanding of skilled nursing facility staff regarding the Washington State Medication Assistant Endorsement Program (MAEP). A 15-item survey was developed and administered to a convenience sample of 218 nursing staff from five eastern Washington nursing homes. Most believed that MAs would not change the cost of care, nor would they enhance or reduce the quality of care provided to residents in skilled nursing facilities. The relatively few Licensed Practical Nurses surveyed (n = 19) were the least in favor of MAs, possibly fearing job loss with the addition of MAs to the staffing mix at their facilities. These factors in combination may reflect why MAEP has not yet been embraced by providers in Washington State. PMID- 26139109 TI - Protein tyrosine phosphatase nonreceptor type 2: an important regulator of lnterleukin-6 production in rheumatoid arthritis synovial fibroblasts. AB - OBJECTIVE: To investigate the role of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) in the pathogenesis of rheumatoid arthritis (RA). METHODS: Synovial tissue samples from patients with RA and patients with osteoarthritis (OA) were stained for PTPN2. Synovial fibroblasts were stimulated with tumor necrosis factor (TNF) and interleukin-1beta (IL-1beta), lipopolysaccharide (LPS), TRAIL, or thapsigargin. The expression of PTPN2 in synovial fibroblasts and peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and Western blotting. Cell death, the release of IL-6 and IL-8, and the induction of autophagy were analyzed after PTPN2 silencing. Methylated DNA immunoprecipitation analysis was used to evaluate DNA methylation-regulated gene expression of PTPN2. RESULTS: PTPN2 was significantly overexpressed in synovial tissue samples from RA patients compared to OA patients. Patients receiving anti-TNF therapy showed significantly reduced staining for PTPN2 compared with patients treated with nonbiologic agents. PTPN2 expression was higher in RA synovial fibroblasts (RASFs) than in OASFs. This differential expression was not regulated by DNA methylation. PTPN2 was further up-regulated after stimulation with TNF, TNF combined with IL-1beta, or LPS. There was no significant difference in basal PTPN2 expression in PBMCs from patients with RA, ankylosing spondylitis, or systemic lupus erythematosus or healthy controls. Most interestingly, PTPN2 silencing in RASFs significantly increased the production of the inflammatory cytokine IL-6 but did not affect levels of IL-8. Moreover, functional analysis showed that high PTPN2 levels contributed to the increased apoptosis resistance of RASFs and increased autophagy. CONCLUSION: This is the first study of PTPN2 in RASFs showing that PTPN2 regulates IL-6 production, cell death, and autophagy. Our findings indicate that PTPN2 is linked to the pathogenesis of RA via synovial fibroblasts. PMID- 26139110 TI - NMR Structures and Interactions of Antimicrobial Peptides with Lipopolysaccharide: Connecting Structures to Functions. AB - Antimicrobial peptides (AMPs) establish the first line of host defense mechanism against invading microorganisms including bacteria, viruses, fungi and parasites. In recent years, emergence and spread of antibiotic resistance bacterial pathogens have dawn considerable interest in investigations of AMPs. The ability of AMPs to exert lethality against multiple drug-resistant (MDR) bacteria has incited promising avenues for antibiotic development. As a mode of action, most AMPs perturb the membrane organization of bacterial cells. The outer membrane lipopolysaccharide (LPS) of Gram-negative bacteria establishes a superior permeability barrier, in contrast to the peptidoglycan layer of Gram-positive bacteria. Due to LPS barrier, development of antibiotics for drug resistant Gram- negative bacteria are more complicated, with only fewer compounds in the pipeline. Recent studies have demonstrated that LPS actively regulate mode of action of AMPs on the lethality of Gram-negative bacteria. LPS, also known as endotoxin, is the primary agent for septic shock syndromes in intensive care unit killing over 120,000 people in the USA. Currently, anti-sepsis therapies are greatly lacking. Therefore, LPS has been considered as a target for the development of antimicrobial and antisepsis drugs. In recent and past few years, 3-D structures and interactions of a number of AMPs have been determined in complex with LPS micelles. These studies have generated molecular insights towards mode of action and synergistic activity of AMPs in the outer membrane. In this review, atomic resolution structures and interactions of potent AMPs with LPS are discussed providing novel insights of their mode of action. PMID- 26139111 TI - Mammalian Antimicrobial Peptides: Promising Therapeutic Targets Against Infection and Chronic Inflammation. AB - Antimicrobial peptides (AMPs) are integral components of the host innate immune system and functional throughout the plant and animal kingdoms. AMPs are short cationic molecules and lethal against a wide range of bacteria, viruses, fungi, yeast and protozoa due to their membranolytic effects on the negatively-charged microbial membranes. In addition, they exert multiple immunomodulatory roles like chemotaxis, modulation of cytokine and chemokine expression, leukocyte activation etc. Since AMPs suffer loss of microbicidal properties under serum and tissue environments, their capacity to modulate the immune system may predominates under the physiological conditions. Discovery of new antibiotics is lagging far behind the rapidly spreading drug resistance among the microorganisms. Both natural and synthetic AMPs have shown promise as 'next generation antibiotics' due to their unique mode of action, which minimises the chance of development of microbial resistance. In addition, they have therapeutic potential against non-infectious diseases like chronic inflammation and cancer. Many of the synthetic AMPs are currently undergoing clinical trials for the treatment of debilitating diseases, such as catheter-related infections, diabetic foot ulcers, chemotherapy associated infections etc. Some of them have already entered the market as topical preparations. In this review, we synopsise the current literature of natural and synthetic AMPs in different infectious and inflammatory diseases of human microfloral habitats, especially the gastrointestinal, respiratory and genitourinary tracts and the skin. We also discuss the classification of AMPs, their mode action and antimicrobial spectrum, including the pathogen evasion mechanisms. In short, we tried to present the locus standi of AMPs in relation to human diseases and highlight the most promising synthetic peptides emerging from the clinical trials. Finally, we focused on the limitations and hurdles in terms of cost of production, bioavailability, pharmacokinetic stability and toxicity faced by commercial development and clinical use of the AMPs and strategies to overcome these hurdles. PMID- 26139112 TI - Antimicrobial Peptide Structure and Mechanism of Action: A Focus on the Role of Membrane Structure. AB - Antimicrobial peptides (AMPs) are showing increasing promise as potential candidate antibacterial drugs in the face of the rapidly emerging bacterial resistance to conventional antibiotics in recent years. The target of these peptides is the microbial membrane and there are numerous models to explain their mechanism of action ranging from pore formation to general membrane disruption. The interaction between the AMP and the target membrane is critical to the specificity and activity of these peptides. However, a precise understanding of the relationship between antimicrobial peptide structure and their cytolytic function in a range of organisms is still lacking. This is a result of the complex nature of the interactions of AMPs with the cell membrane, the mechanism of which can vary considerably between different classes of antimicrobia peptides. A wide range of biophysical techniques have been used to study the influence of a number of peptide and membrane properties on the cytolytic activity of these peptides in model membrane systems. Central to characterisation of this interaction is a quantitative analysis of the binding of peptide to the membrane and the coherent dynamic changes in membrane structure. Recently, dual polarization interferometry has been used to perform an in depth analysis of antimicrobial peptide induced membrane perturbation and with new mass-structure co-fitting kinetic analysis have allowed a real-time label free analysis of binding affinity and kinetics. We review these studies which describe multi-step mechanisms which are adopted by various AMPs in nature and may advance our approach to the development of a new generation of effective antimicrobial therapeutics. PMID- 26139113 TI - Interactions of Antimicrobial Peptides with Bacterial Membranes and Membrane Components. AB - Antimicrobial peptides (AMPs) have attracted considerable recent interest as potential therapeutics, motivated by increasing resistance development against conventional antibiotics. This brief overview summarizes some key aspects related to the interaction of AMPs with bacterial and cell membranes, as well as with membrane components, which is at the core of the mode-of-action of these compounds. Throughout, studies on peptide interactions with model lipid membranes and membrane components are correlated to biological results on antimicrobial and anti-inflammatory effects of AMPs, and translated into therapeutic considerations. PMID- 26139114 TI - Naturally Occurring Peptides from Rana temporaria: Antimicrobial Properties and More. AB - The extensive search for alternative therapeutics against microbial pathogens has led to the discovery of cationic peptides as new anti-infectives with a novel mode of action. Particular interest has been devoted to small linear peptides that can be efficiently made by chemical synthesis at competitive costs. The most promising originate from a large family of short, naturally occurring peptides found in the skin of amphibia of Rana genus, i.e. the temporins. This review is mainly focused on the recent structure-function studies of the earliest known temporin isoforms (TA, TB and TL) and their potential clinical role as novel antimicrobial agents. The development of novel antibiotics is an urgent public health concern due to the increased resistance of microorganisms to conventional antibiotics, particularly in the hospital setting. PMID- 26139115 TI - Non-Membrane Permeabilizing Modes of Action of Antimicrobial Peptides on Bacteria. AB - Antimicrobial peptides (AMPs) are a large class of innate immunity effectors with a remarkable capacity to inactivate microorganisms. Their ability to kill bacteria by membranolytic effects has been well established. However, a lot of evidence points to alternative, non-lytic modes of action for a number of AMPs, which operate through interactions with specific molecular targets. It has been reported that non-membrane-permeabilizing AMPs can bind to and inhibit DNA, RNA or protein synthesis processes, inactivate essential intracellular enzymes, or affect membrane septum formation and cell wall synthesis. This minireview summarizes recent findings on these alternative, non-lytic modes of antimicrobial action with an emphasis to the experimental approaches used to clarify each step of their intracellular action, i.e. the cell penetration mechanism, intracellular localization and molecular mechanisms of antibacterial action. Despite the fact that such data exists for a large number of peptides, our analysis indicates that only for a small number of AMPs sufficient data have been collected to support a mode of action with an authentic and substantial contribution by intracellular targeting. In most cases, peptides with non-lytic features have not been thoroughly analyzed, or only a single aspect of their mode of action has been taken into consideration and therefore their mechanism of action can only be hypothesized. A more detailed knowledge of this class of AMPs would be important in the design of novel antibacterial agents against unexploited targets, endowed with the capacity to penetrate into pathogen cells and kill them from within. PMID- 26139116 TI - Structure-Function Relationships of Antimicrobial Peptides and Proteins with Respect to Contact Molecules on Pathogen Surfaces. AB - The Antimicrobial peptides (e.g. defensins, hevein-like molecules and food protecting peptides like nisin) are able to interact specifically with contact structures on pathogen surfaces. Besides protein receptors, important recognition points for such contacts are provided by pathogen glycan chains or surface lipids. Therefore, structural data concerning surface exposed glycans and lipids are of the highest clinical interest since these recognition functions play a key role when optimising anti-infection therapies. Approaches in nanomedicine and nanopharmacology in which various biophysical techniques such as NMR (Nuclear Magnetic Resonance), AFM (Atomic Force Microscopy), SPR (Surface Plasmon Resonance) and X-ray crystallography can be combined with biochemical and cell biological methods will lead to improved antimicrobial peptides by this rational drug design approach. Such a strategy is extremely well suited to support clinical studies focussing on an effective fight against multiresistant pathogens. The data sets which are described here can be considered as universal for the design of various antimicrobial drugs against certain pathogens (bacteria, viruses and fungi) which cause severe diseases in humans and animals. Furthermore, these insights are also helpful for progressing developments in the field of food conservation and food preservation. A detailed analysis of the structure-function relationships between antimicrobial peptides and contact molecules on pathogen surfaces at the sub-molecular level will lead to a higher degree of specificity of antimicrobial peptides. PMID- 26139117 TI - Model Membrane and Cell Studies of Antimicrobial Activity of Melittin Analogues. AB - Melittin is a 26 residue peptide and the major component of bee (Apis mellifera) venom. Although melittin has both anticancer and antimicrobial properties, utilization has been limited due to its high lytic activity against eukaryotic cells. The mechanism of this lytic activity remains unclear but several mechanisms have been proposed, including pore formation or a detergent like mechanism, which result in lysis of cell membranes. Several analogues of melittin have been synthesized to further understand the role of specific residues in its antimicrobial and lytic activity. Melittin analogues that have a proline residue substituted for an alanine, lysine or cysteine have been studied with both model membrane systems and living cells. These studies have revealed that the proline residue plays a critical role in antimicrobial activity and cytotoxicity. Analogues lacking the proline residue and dimers of these analogues displayed decreased cytotoxicity and minimum inhibition concentrations. Several mutant studies have shown that, when key substitutions are made, the resultant peptides have more activity in terms of pore formation than the native melittin. Designing analogues that retain antimicrobial and anticancer activity while minimizing haemolytic activity will be a promising way to utilize melittin as a potential therapeutic agent. PMID- 26139118 TI - Magainin 2-PGLa Interactions in Membranes - Two Peptides that Exhibit Synergistic Enhancement of Antimicrobial Activity. AB - The structural requirements for the synergistic enhancement of antimicrobial activities of the cationic linear peptides PGLa and magainin 2 were investigated. In a first step the antimicrobial activities were evaluated for a number of modifications of the sequences and equimolar mixtures thereof. In particular fluorophore labelled peptides maintain a high degree of antimicrobial activity and considerable synergism when tested conjointly. Thereafter, circular dichroism spectroscopy indicated that these extended sequences adopt helical conformations in the presence of model membranes similar to the unmodified sequences. Energy transfer between the fluorophores suggested that the peptides reside in close proximity to each other when bound to the membrane surface at high concentrations. The fluorophore interactions quickly diminish at lower peptide-to lipid ratios indicating that the peptide-peptide interactions are weak. Furthermore, (15)N solid-state NMR measurements of the membrane topology of [(15)N-Ala14]-PGLa and of its fluorophorecarrying analogue reconstituted into supported 1, 2-didecanoyl-sn-glycero-3-phosphocholine bilayers were performed. These experiments revealed no correlation between the topological state of PGLa and the observed synergistic enhancement of antimicrobial activities due to the presence of magainins. These results suggest that lipid mediated interactions rather than the formation of tight peptide-peptide complexes in the membrane are responsible for synergistic activities of the mixtures. PMID- 26139119 TI - Antimicrobial Peptides and their Pore/Ion Channel Properties in Neutralization of Pathogenic Microbes. AB - The essence of successful antimicrobial chemotherapy lies in selective toxicity of the agent towards the pathogen. An ideal antimicrobial agent should kill pathogens effectively with little or no effect on host cells. There is a dearth of antibiotic and antimicrobial therapies due the rapid development of microbial resistance to these agents, as evidenced by increasing incidences of hospital acquired infections. This challenge necessitates the discovery and development of novel and effective antimicrobial agents. One promising approach is Antimicrobial Peptides (AMPs), which are synthesized by a large number of organisms. The presence of AMPs throughout evolution hints at their importance. The first and foremost interaction between AMPs and target cell occurs at the membrane of the pathogen. The details about these interactions will pave way for the development of new synthetic analogues or modified analogues of existing AMPs. Mechanistic insights into adoption of different structures in presence of bacterial membranes (and with their specific targets) will enhance our understanding and knowledge about these agents and their detailed mechanism of action. AMPs interact with lipids and form lipid-AMP complexes that create AMP-lined ion channels, which in turn modulate the membrane potential. This may have an effect on various biological processes leading to arrest of cell growth or cell death. This review summarizes the ion channel formation property of AMPs as an effective approach in dealing with neutralization of pathogenic microbes. PMID- 26139120 TI - Cost-effectiveness of nanomedicine: the path to a future successful and dominant market? PMID- 26139121 TI - Targeted combination nanotherapeutics in cancer a real promise. PMID- 26139122 TI - Recent nanomedicine articles of outstanding interest. PMID- 26139123 TI - The promotion of salinomycin delivery to hepatocellular carcinoma cells through EGFR and CD133 aptamers conjugation by PLGA nanoparticles. AB - AIMS: To develop salinomycin-loaded poly(lactic-co-glycolic acid) nanoparticles conjugated with both CD133 aptamers A15 and EGFR aptamers CL4 (CESN), to target hepatocellular carcinoma (HCC) cells simultaneously expressing EGFR and CD133. MATERIALS & METHODS: The antitumor activity and mechanism of CESN were investigated. RESULTS & CONCLUSION: The cytotoxicity of CESN in HCC cells and CD133(+) HCC cells was superior to that of A15 or CL4-conjugted or nontargeted salinomycin-loaded nanoparticles. The antitumor assay in mice bearing HCC xenograft tumors confirmed the superior antitumor activity of CESN over other controls. We speculated that the improved therapeutic effect of CESN may be attributed to both targeting a higher percentage of HCC cells and increased delivery of salinomycin to HCC cells. PMID- 26139125 TI - Development of a multimodal imaging probe by encapsulating iron oxide nanoparticles with functionalized amphiphiles for lymph node imaging. AB - AIM: We tried to develop a multimodal iron oxide nanoparticles (IO NP) imaging probe by an encapsulation method using specific amphiphiles for (68)Ga-labeling and lymph node-targeting. MATERIALS & METHODS: Nanoparticles (NPs) were encapsulated with a solution containing polysorbate 60 and the amphiphiles. The prepared NPs were labeled with (68)Ga and tested in vitro and in vivo. RESULTS: Prepared 1,4,7-triazacyclononane-1,4,7-triacetic acid-IO-Mannose (NOTA-IO-Man) showed a narrow size distribution, and no significant aggregation or degradation under harsh conditions. The relaxivity coefficient of (68)Ga-NOTA-IO-Man was higher than that of ferumoxide. The accumulation of (68)Ga-NOTA-IO-Man in the lymph node after injection into rat's footpad was confirmed by both positron emission tomography and MRI. CONCLUSION: We successfully developed PET/MRI dual modality imaging probe targeting lymph nodes by using the facile encapsulation method. PMID- 26139124 TI - New approach to develop ultra-high inhibitory drug using the power function of the stoichiometry of the targeted nanomachine or biocomplex. AB - AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number. METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population. RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with stoichiometry 1000 > 6 > 1. Complete inhibition of virus replication was found when Z = 6. CONCLUSION: Drug inhibition potency depends on the stoichiometry of the targeted components of the biocomplex or nanomachine. The inhibition effect follows a power function of the stoichiometry of the target biocomplex. PMID- 26139127 TI - Disulfide-bridged cleavable PEGylation in polymeric nanomedicine for controlled therapeutic delivery. AB - PEGylation in polymeric nanomedicine has gained substantial predominance in biomedical applications due to its resistance to protein absorption, which is critically important for a therapeutic delivery system in blood circulation. The shielding layer of PEGylation, however, creates significant steric hindrance that negatively impacts cellular uptake and intracellular distribution at the target site. This unexpected effect compromises the biological efficacy of the encapsulated payload. To address this issue, one of the key strategies is to tether the disulfide bond to PEG for constructing a disulfide-bridged cleavable PEGylation. The reversible disulfide bond can be cleaved to enable selective PEG detachment. This article provides an overview on the strategy, method and progress of PEGylation nanosystem with the cleavable disulfide bond. PMID- 26139128 TI - Nanofibers used for delivery of antimicrobial agents. AB - Nanotechnology has gained an increased interest in several different areas of biotechnology including the drug delivery via nanofibers. Self-assembly, phase separation and electrospinning can all be used to successfully generate nanofibers with sizes well within the range of those of the fibers present in the native extracellular matrix (50-500 nm). In this article, the authors introduced the most popular applications of nanofibers related to the delivery of antimicrobial agents for infectious diseases. To date, only a few in-vivo studies are available at present to demonstrate its clinical potential; most of the studies are of exploratory nature and rely mostly on in-vitro experiments. Therefore, further advancement in the production and clinical performance of drug loaded nanofibrous matrices seems necessary. PMID- 26139126 TI - Enabling cytoplasmic delivery and organelle targeting by surface modification of nanocarriers. AB - Nanocarriers are designed to specifically accumulate in diseased tissues. In this context, targeting of intracellular compartments was shown to enhance the efficacy of many drugs and to offer new and more effective therapeutic approaches. This is especially true for therapies based on biologicals that must be encapsulated to favor cell internalization, and to avoid intracellular endosomal sequestration and degradation of the payload. In this review, we discuss specific surface modifications designed to achieve cell cytoplasm delivery and to improve targeting of major organelles; we also discuss the therapeutic applications of these approaches. Last, we describe some integrated strategies designed to sequentially overcome the biological barriers that separate the site of administration from the cell cytoplasm, which is the drug's site of action. PMID- 26139130 TI - Corrigendum. PMID- 26139129 TI - Nanotechnology for enrichment and detection of circulating tumor cells. AB - Circulating tumor cells (CTCs) are a hallmark of invasive behavior of cancer, responsible for the development of metastasis. Their detection and analysis have significant impacts in cancer biology and clinical practice. However, CTCs are rare events and contain heterogeneous subpopulations, requiring highly sensitive and specific techniques to identify and capture CTCs with high efficiency. Nanotechnology shows strong promises for CTC enrichment and detection owning to the unique structural and functional properties of nanoscale materials. In this review, we discuss the CTC enrichment and detection technologies based on a variety of functional nanosystems and nanostructured substrates, with the goal to highlight the role of nanotechnology in the advancement of basic and clinical CTC research. PMID- 26139131 TI - Imaging stress. AB - Recent innovations in cell biology and imaging approaches are changing the way we study cellular stress, protein misfolding, and aggregation. Studies have begun to show that stress responses are even more variegated and dynamic than previously thought, encompassing nano-scale reorganization of cytosolic machinery that occurs almost instantaneously, much faster than transcriptional responses. Moreover, protein and mRNA quality control is often organized into highly dynamic macromolecular assemblies, or dynamic droplets, which could easily be mistaken for dysfunctional "aggregates," but which are, in fact, regulated functional compartments. The nano-scale architecture of stress-response ranges from diffraction-limited structures like stress granules, P-bodies, and stress foci to slightly larger quality control inclusions like juxta nuclear quality control compartment (JUNQ) and insoluble protein deposit compartment (IPOD), as well as others. Examining the biochemical and physical properties of these dynamic structures necessitates live cell imaging at high spatial and temporal resolution, and techniques to make quantitative measurements with respect to movement, localization, and mobility. Hence, it is important to note some of the most recent observations, while casting an eye towards new imaging approaches that offer the possibility of collecting entirely new kinds of data from living cells. PMID- 26139133 TI - New flexible endoscopic controlled stapler technique for the treatment of Zenker's diverticulum. AB - OBJECTIVE: Zenker's diverticulum (ZD) is a rare cause of dysphagia. Various surgical and flexible endoscopic therapies are available with either higher morbidity or either higher recurrence rate. Therefore, improved treatment options are needed. MATERIAL AND METHODS: This case report involves an 83-year-old female patient with symptomatic ZD. Under flexible endoscopic control, a new 5 mm fully rotatable surgical stapler was used for the dissection of the septum between the ZD and the esophageal lumen. An ultrathin endoscope and the 5 mm stapler were introduced together through a flexible overtube under conscious sedation. RESULTS: ZD treatment with this new stapler technique was feasible and effective in our patient. Procedure time was 10 min. Clinical symptoms improved immediately and the patient could be discharged the day after the procedure. CONCLUSION: The described stapler technique under flexible endoscopic control is the first report of this new treatment option for ZD. This new technique under conscious sedation may have some potential advantages compared to standard techniques such as better long-term results and lower complication rates. Further studies are needed. PMID- 26139134 TI - Cooperative urban mining in Brazil: Collective practices in selective household waste collection and recycling. AB - Solid waste is a major urban challenge worldwide and reclaiming the resources embedded in waste streams, involving organized recyclers, is a smart response to it. Informal and organized recyclers, mostly in the global south, already act as important urban miners in resource recovery. The paper describes the complex operations of recycling cooperatives and draws attention to their economic, environmental, and social contributions. A detailed discussion based on empirical data from the recycling network COOPCENT-ABC in metropolitan Sao Paulo, Brazil, contextualizes this form of urban mining. The analysis is situated within Social and Solidarity Economy (SSE) and Ecological Economy (EE) theory. Current challenges related to planning, public policy, and the implementation of cooperative recycling are analysed on the level of individual recyclers, cooperatives, municipalities and internationally. There are still many hurdles for the informal, organized recycling sector to become recognized as a key player in efficient material separation and to up-scale these activities for an effective contribution to the SSE and EE. Policies need to be in place to guarantee fair and safe work relations. There is a win-win situation where communities and the environment will benefit from organized urban mining. PMID- 26139132 TI - The detection and role of heat shock protein 70 in various nondisease conditions and disease conditions: a literature review. AB - As an intracellular polypeptide, heat shock protein 70 (HSP70) can be exposed on the plasma membrane and/or released into the circulation. However, the role of HSP70 in various nondisease and disease conditions remains unknown. Quantitative methods for the detection of HSP70 have been used in clinical studies, revealing that an increase in circulating HSP70 is associated with various types of exercise, elderly patients presenting with inflammation, mobile phones, inflammation, sepsis, chronic obstructive pulmonary disease, asthma, carotid intima-media thickness, glutamine-treated ill patients, mortality, diabetes mellitus, active chronic glomerulonephritis, and cancers. Circulating HSP70 decreases with age in humans and in obstructive sleep apnea, arteriosclerosis, atrial fibrillation (AF) following coronary artery bypass surgery, nonalcoholic fatty liver disease, moderate-to-severe alcoholic fatty liver disease, hepatic steatosis, and Helicobacter pylori infection. In conclusion, quantitative methods can be used to detect HSP70, particularly in determining circulating HSP70 levels, using more convenient and rapid screening methods. Studies have shown that changes in HSP70 are associated with various nondisease and disease conditions; thus, HSP70 might be a novel potential biomarker reflecting various nondisease conditions and also the severity of disease conditions. However, the reliability and accuracy, as well as the underlying mechanism, of this relationship remain poorly understood, and large-sample clinical research must be performed to verify the role. PMID- 26139135 TI - Inhibitory effect of high NH4(+)-N concentration on anaerobic biotreatment of fresh leachate from a municipal solid waste incineration plant. AB - Fresh leachate from municipal solid waste (MSW) incineration plants generally contains extremely high NH4(+)-N concentration which could inhibit the bioactivity of microorganisms. The inhibitory effect of high NH4(+)-N concentration on anaerobic biotreatment of fresh leachate from a MSW incineration plant in China has been investigated in this study. The inhibition processes was studied by both static tests and a laboratory-scale expanded granular sludge bed (EGSB) reactor. The specific methanogenic activity (SMA) of the microorganisms in anaerobic granular sludge was inhibited with the NH4(+)-N concentration increasing to 1000mg/L in static tests. As well the chemical oxygen demand (COD) removal efficiency and the methane yield decreased in the EGSB reactor, while the volatile fatty acids (VFAs) accumulated and extracellular polymeric substances (EPS) of the anaerobic granular sludge increased with NH4(+)-N concentration rising to 1000mg/L, without any rebounding during 30days of operation. Decreasing NH4(+)-N concentration to 500mg/L in influent, the COD removal efficiency recovered to about 85% after 26days. 1000mg/L of NH4(+)-N in leachate was suggested to be the inhibition threshold in EGSB reactor. High-throughput sequencing results showed little changes in microbial communities of the sludge for a high NH4(+)-N concentration, indicating that the survival of most microorganisms was not affected under such a condition. It inhibited the bioactivity of the microorganisms, resulting in decrease of the COD removal efficiency. PMID- 26139136 TI - Optimisation of sewage sludge anaerobic digestion through co-digestion with OFMSW: Effect of collection system and particle size. AB - The effect of organic fraction of municipal solid waste (OFMSW) loading rate and particulate size on the sewage sludge (SS) mesophilic anaerobic co-digestion was assessed in continuous stirred tank reactor at hydraulic retention time of 20days. The SS-OFMSW mixture composed by 54% of the volatile solids fed (inlet VS), at OLR of 3.1kgCODm(-3)d(-1) (1.9kgVSm(-3)d(-1)), showed the highest increment on the volumetric methane production and yield of +200% and +59% respectively, under stable conditions. The effect of particulate size was assessed with the same mixture and same operational conditions but reducing the OFMSW particulate size from 20mm to 8mm with the aim to improve the hydrolysis step, but the results showed any influence in the OFMSW particulate size range analysed. In addition, specific biomass activity was assessed at the end of each co-digestion period. Results showed that OFMSW promoted beta-oxidation syntrophic acetogens and the acetoclastic methanogens activity; although the last increase of the OFMSW percentage (from 47% to 54% inlet-VS) affected negatively the specific substrate activity, but not inhibitory effect was observed. Therefore, the results obtained in the continuous experiment could be related with some inhibitory or toxic effect and not due to hydrolysis limitation. The specific biomass activity test was demonstrated to be an interesting tool to evaluate and control the co-digestion process, especially when conventional parameters did not explain the behaviour of the biological system. PMID- 26139137 TI - Mechanical pre-treatment of mobile phones and its effect on the Printed Circuit Assemblies (PCAs). AB - The recycling of Waste Electrical and Electronic Equipment (WEEE) has attracted a notable amount of interest during the last few decades due to the high metal concentrations and substantial increase in the growth rate of WEEE. In addition, higher recovery and recycling rates required by the European Union demand more comprehensive treatment of WEEE. However, complex product design and the presence of harmful substances together with low concentrations of special metals present challenges for processing. This study examines the effect of mechanical treatment of mobile phones on metal concentrations in the printed circuit assembly (PCA) fraction compared to manual dismantling. The designed mechanical treatment process including crushing, sieving, magnetic-, eddy current- and sensor-based separation was able to separate plastics, ferrous metals, PCA and stainless steel for further treatment. The process separated PCA with an efficiency of 85%. However, the quality of the separated PCAs was poor compared with "pure" manually dismantled PCAs. The primary crushing of mobile phones destroys PCAs thus resulting in the loss of especially precious metals used in the connector coatings and in the surface-mounted components. As a result, the theoretical value of the produced PCA fraction is only half compared to using manual dismantling. However, high labour costs in western countries and low capacity may hinder the feasibility of hand dismantling. PMID- 26139138 TI - No walking away. PMID- 26139139 TI - Quick lessons on environmental nanotech. PMID- 26139141 TI - DNA nanotechnology: Measuring chloride in live cells. PMID- 26139142 TI - Spintronics: Skyrmions under strain. PMID- 26139143 TI - Perovskite photovoltaics: Signs of stability. PMID- 26139145 TI - Inspiration is all around you. PMID- 26139144 TI - Catalysis by clusters with precise numbers of atoms. AB - Clusters that contain only a small number of atoms can exhibit unique and often unexpected properties. The clusters are of particular interest in catalysis because they can act as individual active sites, and minor changes in size and composition--such as the addition or removal of a single atom--can have a substantial influence on the activity and selectivity of a reaction. Here, we review recent progress in the synthesis and characterization of well-defined subnanometre clusters, and the understanding and exploitation of their catalytic properties. We examine work on size-selected supported clusters in ultrahigh vacuum environments and under realistic reaction conditions, and explore the use of computational methods to provide a mechanistic understanding of their catalytic properties. We also highlight the potential of size-selected clusters to provide insights into important catalytic processes and their use in the development of novel catalytic systems. PMID- 26139147 TI - Influence of Age and HLA Alleles on the CMV-Specific Cell-Mediated Immunity Among CMV-Seropositive Kidney Transplant Candidates. PMID- 26139146 TI - TOX and CDKN2A/B Gene Polymorphisms Are Associated with Type 2 Diabetes in Han Chinese. AB - To study associations between type 2 diabetes (T2DM) candidate genes and microvascular complications of diabetes (MVCDs), we performed case-control association studies for both T2DM and MVCDs in Han Chinese subjects. We recruited 1,939 unrelated Han Chinese T2DM patients and 918 individuals with normal blood glucose levels as nondiabetic controls. Among T2DM patients, 1116 have MVCDs, 266 have a history of T2DM of >10 years but never developed MVCDs. Eighty-two single nucleotide polymorphisms (SNPs) in 54 candidate genes were genotyped. Discrete association studies were performed by the PLINK program for T2DM and MVCDs. Significant associations were found among candidate gene SNPs and T2DM, including rs1526167 of the TOX gene (allele A, P = 2.85 * 10(-9), OR = 1.44). The SNP rs10811661 of the CDKN2A/B gene was also associated with T2DM (allele T, P = 4.09 * 10(-7), OR = 1.36). When we used control patients with >10 years of T2DM history without MVCD, we found that the G allele of SNP rs1526167 of the TOX gene was associated with MVCD (nominal P = 4.33 * 10(-4)). In our study, significant associations were found between TOX and CDKN2A/B gene SNPs and T2DM. The TOX polymorphism might account for the higher risk of T2DM and the lower risk of MVCDs in the Han Chinese population. PMID- 26139148 TI - Unprecedented Transformation of a Directing Group Generated In Situ and Its Application in the One-Pot Synthesis of 2-Alkenyl Benzonitriles. AB - An unprecedented protocol for the transformation of benzoyl azides into benzonitrile derivatives via iminophosphoranes generated in situ is described. The strategy was successfully applied to the de-novo synthesis of 2-alkenylated benzonitrile derivatives from benzoyl azides through ortho C-H activation/alkenylation followed by subsequent rearrangement. The salient features of this protocol involve incorporation of two important functionalities through cyanation and olefination in one pot under mild reaction conditions by using a less expensive Ru catalyst. The mechanism was established by isolating and characterising (using (31) P NMR) an intermediate with two ortho functionalities, iminophosphorane and olefin, under specific reaction conditions. PMID- 26139149 TI - Comment on Zhao et al. "Palmoplantar keratoderma of the Gamborg-Nielsen type is caused by mutations in the SLURP1 gene and represents a variant of Mal de Meleda". PMID- 26139150 TI - Machine learning plus optical flow: a simple and sensitive method to detect cardioactive drugs. AB - Current preclinical screening methods do not adequately detect cardiotoxicity. Using human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs), more physiologically relevant preclinical or patient-specific screening to detect potential cardiotoxic effects of drug candidates may be possible. However, one of the persistent challenges for developing a high-throughput drug screening platform using iPS-CMs is the need to develop a simple and reliable method to measure key electrophysiological and contractile parameters. To address this need, we have developed a platform that combines machine learning paired with brightfield optical flow as a simple and robust tool that can automate the detection of cardiomyocyte drug effects. Using three cardioactive drugs of different mechanisms, including those with primarily electrophysiological effects, we demonstrate the general applicability of this screening method to detect subtle changes in cardiomyocyte contraction. Requiring only brightfield images of cardiomyocyte contractions, we detect changes in cardiomyocyte contraction comparable to - and even superior to - fluorescence readouts. This automated method serves as a widely applicable screening tool to characterize the effects of drugs on cardiomyocyte function. PMID- 26139151 TI - A review of the safety and efficacy data for insulin glargine 300 units/ml, a new formulation of insulin glargine. AB - Insulin glargine 100 units/ml (Gla-100) has become a standard of care in diabetes treatment over the past decade, providing 24-h basal insulin coverage after once daily subcutaneous injection for many people with diabetes, with a well established efficacy and safety profile. New insulin glargine 300 units/ml (Gla 300) is a basal insulin that provides the same number of units as Gla-100 in a third of the volume. Compared with Gla-100, Gla-300 has shown more constant and prolonged pharmacokinetic (PK)/pharmacodynamic (PD) profiles. This review summarizes the findings from the EDITION series of clinical trials that investigated Gla-300 in individuals with type 1 and type 2 diabetes mellitus. Overall, Gla-300 has been shown to achieve similar glycaemic control with less, or similar, nocturnal hypoglycaemia compared with Gla-100, and a trend towards lower hypoglycaemia at any time of day. The EDITION series of clinical trials also provides some evidence for less weight gain with Gla-300 than with Gla-100. In addition, the PK/PD profiles of Gla-300 may allow more flexibility in the timing of doses, improving convenience; thus, Gla-300 could offer several positive features for individuals with diabetes requiring basal insulin therapy. PMID- 26139152 TI - Transcranial direct current stimulation as a tool in the study of sensory perceptual processing. AB - Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique with increasing popularity in the fields of basic research and rehabilitation. It is an affordable and safe procedure that is beginning to be used in the clinic, and is a tool with potential to contribute to the understanding of neural mechanisms in the fields of psychology, neuroscience, and medical research. This review presents examples of investigations in the fields of perception, basic sensory processes, and sensory rehabilitation that employed tDCS. We highlight some of the most relevant efforts in this area and discuss possible limitations and gaps in contemporary tDCS research. Topics include the five senses, pain, and multimodal integration. The present work aims to present the state of the art of this field of research and to inspire future investigations of perception using tDCS. PMID- 26139155 TI - Young scientists' congress in Brussels. PMID- 26139154 TI - A new method for evaluating the risk of transferring leukemic cells with transplanted cryopreserved ovarian tissue. AB - PURPOSE: This study aimed to develop a method to detect ovarian residual disease by multicolor flow cytometry in acute leukemia patients. METHODS: We designed an experimental model consisting in adding acute leukemia cells to a cell suspension obtained from healthy ovarian cortex. Leukemic cell detection within the ovarian cell suspension required the development of a specific myeloid antibody panel different from that commonly used for minimal residual disease (MRD) monitoring in bone marrow. The method was then used to detect ovarian residual disease in 11 acute leukemia patients. RESULTS: Multicolor flow cytometry is able to evaluate the presence of viable leukemic cells in the ovarian cortex with good specificity and robust sensitivity of 10-4. We observed a good correlation between multicolor flow cytometry and quantitative polymerase chain reaction results. Ovarian residual disease detection by multicolor flow cytometry was positive in 3 out of 11 acute leukemia patients. CONCLUSION: Multicolor flow cytometry can potentially be applied to ovarian tissue from all acute leukemia patients and is essential to evaluate the risk of cancer re-seeding before autograft of ovarian tissue in case of acute leukemia. PMID- 26139153 TI - Characterisation of anaemia and associated factors among infants and pre schoolers from rural India. AB - OBJECTIVE: In India, national databases indicate anaemia prevalence of 80 % among 6-35-month-old children and 58 % among 36-59-month-old children. The present study aimed to characterise anaemia and the associated factors among infants and pre-schoolers living in rural India. DESIGN: Multivariate logistic regression analysis of data collected prior to an intervention trial. Fe-deficiency with anaemia (IDA), Fe deficiency with no anaemia (IDNA) and anaemia without Fe deficiency were defined. Serum ferritin, soluble transferrin receptor (sTfR) and sTfR/log ferritin index were used to indicate Fe status. SETTING: Twenty-six villages of Nalgonda district, Telangana, India. Data were collected in community sites. Participants Four hundred and seventy-six infants (aged 6-12 months), 316 pre-schoolers (aged 29-56 months) and their mothers. RESULTS: Prevalence of anaemia among infants and pre-schoolers was 66.4 and 47.8 %, prevalence of IDA was 52.2 and 42.1 %, prevalence of IDNA was 22.2 and 29.8 %, prevalence of anaemia without Fe deficiency was 14.2 and 5.7 %. Among infants, anaemia was positively associated with maternal anaemia (OR=3.31; 95 % CI 2.10, 5.23; P<0.001), and sTfR/log ferritin index (OR=2.21; 95 % CI 1.39, 3.54; P=0.001). Among pre-schoolers, anaemia was positively associated with maternal anaemia (OR=3.77; 95 % CI 1.94, 7.30; P<0.001), sTfR/log ferritin index (OR=5.29; 95 % CI 2.67, 10.50; P<0.001), high C-reactive protein (OR=4.39; 95 % CI 1.91, 10.06, P<0.001) and young age (29-35 months: OR=1.92; 05 % CI 1.18, 3.13, P=0.009). CONCLUSIONS: Anaemia prevalence continues to be high among infants and pre schoolers in rural India. Based on sTfR/ferritin index, Fe deficiency is a major factor associated with anaemia. Anaemia is also associated with inflammation among pre-schoolers and with maternal anaemia among infants and pre-schoolers, illustrating the importance of understanding the aetiology of anaemia in designing effective control strategies. PMID- 26139156 TI - Association of WNT4 polymorphisms with endometriosis in infertile patients. AB - PURPOSE: Recently, several genome-wide association studies have demonstrated an association between endometriosis and markers located in or near to WNT4 gene. In order to assess the validity of the findings, we conducted a replication case control study in a Brazilian population. METHODS: Genetic association study comprising 400 infertile women with endometriosis and 400 fertile women as controls. TaqMan allelic discrimination technique was used to investigate the relationship between endometriosis and four single-nucleotide polymorphisms (rs16826658, rs3820282, rs2235529, and rs7521902) in WNT4 gene. Genotype distribution, allele frequency, and haplotype analysis of the WNT4 polymorphisms were performed. A p value <0.05 was considered significant. RESULTS: The results revealed a significant association of rs16826658 (p = 7e-04) and rs3820282 (p = 0.048) single-nucleotide polymorphisms (SNPs) on WNT4 gene with endometriosis related infertility, while rs2235529 and rs7521902 SNPs showed no difference between cases and controls. CONCLUSIONS: Our results suggested that rs16826658 and rs3820282 polymorphisms on WNT4 gene might be involved in the pathogenesis of endometriosis in the infertile women studied. Analysis of WNT4 genetic variants might help to identify patients at high risk for disease development. PMID- 26139157 TI - Oocyte cryopreservation beyond cancer: tools for ethical reflection. AB - PURPOSE: This article offers physicians a tool for structured ethical reflection on challenging situations surrounding oocyte cryopreservation in young healthy women. METHODS: A systematic literature review offers a comprehensive overview of the ethical debate surrounding the practice. Ethical Counseling Methodology (ECM) offers a practical approach for addressing ethical uncertainties. ECM consists of seven steps: (i) case presentation; (ii) analysis of possible implications; (iii) presentation of ethical question(s); (iv) explanation of ethical terms; (v) presentation of the ethical arguments in favor of and against the procedure; (vi) examination of the individual patient's beliefs and wishes; and (vii) conclusive summary. RESULTS: The most problematic aspects in the ethical debate include the distinction between medical and non-medical use of oocyte cryopreservation, safety and efficiency of the procedure, and marketing practices aimed at healthy women. Female empowerment and enhanced reproductive choices (granted oocyte cryopreservation is a safe and efficient technique) are presented as ethical arguments supporting the practice, while ethical reservations towards oocyte cryopreservation are based on concerns about maternal and fetal safety and wider societal implications. CONCLUSIONS: Oocyte cryopreservation is gaining popularity among healthy reproductive age women. However, despite promised benefits it also involves risks that are not always properly communicated in commercialized settings. ECM offers clinicians a tool for structured ethical analysis taking into consideration a wide range of implications, various ethical standpoints, and patients' perceptions and beliefs. PMID- 26139158 TI - Birth of a healthy child after preimplantation genetic screening of embryos from sperm of a man with non-mosaic Down syndrome. AB - PURPOSE: The purpose of this study is to present a case of healthy infant born after intracytoplasmic sperm injection-in vitro fertilization (ICSI-IVF) with preimplantation genetic screening (PGS) using sperm from a man with non-mosaic trisomy 21 and a literature review. MATERIALS AND METHODS: A 26-year-old euploid female and 29-year-old male with non-mosaic trisomy 21 and male factor undergoing ICSI-IVF treatment for primary infertility with embryo biopsy for PGS with comprehensive chromosomal screening (CCS) presented to the Infertility Clinic at Highland Hospital, the Alameda County Medical Center, California, with 6-year history of primary infertility. The outcome measure is a live birth of a healthy child and ploidy status of biopsied blastocysts. RESULTS: Egg retrieval yielded 33 oocytes, 29 of which underwent ICSI with ejaculated sperm. Twenty-eight 2PN zygotes were cultured, and 13 blastocysts underwent trophectoderm biopsy and vitrification 5 or 6 days after retrieval. CCS analysis revealed that 12 out of 13 (92 %) of blastocysts were euploid and one was a complex abnormal mosaic. Transfer of two grade I hatching blastocysts resulted in a singleton pregnancy with normal prenatal genetic screening and delivery of a healthy male infant at 41 weeks via primary cesarean section for non-reassuring fetal status. CONCLUSION: This is the first report of a live birth of a healthy child after ICSI-IVF with PGS using ejaculated sperm from a man with non-mosaic trisomy 21 and male factor infertility. PMID- 26139159 TI - Long-term results with the laparoscopic transposition of renal lower pole crossing vessels. AB - BACKGROUND: For the treatment of ureterovascular pelviureteric junction obstruction (PUJO), transposition of lower pole crossing vessels (LPCV) has been described as an alternative to dismembered pyeloplasty. PURPOSE: To report on the long-term follow-up of children after laparoscopic transposition of LPCV. METHODS: A retrospective analysis of 70 children consecutively treated by laparoscopic transposition of LPCV. Candidate patients were selected on the basis of clinical history, renal ultrasound (US), and pre-operative mercaptoacetyltriglycine (MAG-3) scan. Selection criteria included: presence of LPCV with SFU Grade 1-2 hydronephrosis, impaired drainage on MAG-3 and intraoperative normal pelviureteric junction (PUJ) and ureter peristalsis. Thinned parenchyma, impaired renal function, or history of prenatal hydronephrosis were not considered as exclusion criteria. Children were clinically followed up with US and MAG-3 scan. Success was defined by symptom resolution with improvement in hydronephrosis. RESULTS: Seventy children, aged 8.3 years (range 2.75-16.0), were selected. Procedures were performed through transperitoneal laparoscopy (n = 42) or were robotic-assisted (n = 28). Operative time was 120 min and length of hospital stay was 2 days. The outcome was successful in 67/70 patients (96%), with a median follow-up of 52 months (range 13-114). There were three failures in children who eventually underwent dismembered pyeloplasty for a symptomatic, undiagnosed, intrinsic PUJ obstruction. Two of them had been postnatally followed for a resolving prenatally diagnosed hydronephrosis. Three children became free of symptoms, had improved hydronephrosis, but still showed impaired drainage on MAG-3 and are being closely followed up. DISCUSSION: Although this procedure proves to have long-term efficiency in selected indications, the main challenge is to intraoperatively ascertain the absence of associated intrinsic stenosis. Objective criteria remain difficult to establish, but intraoperative findings, including dependent, funnel shaped, normal-looking PUJ with decreasing hydronephrosis after pelvis and LPCV mobilisation, and efficient peristalsis across the PUJ under intraoperative diuretic test, represent a low likelihood of associated intrinsic stenosis. Ipsilateral impaired renal function doesn't seem to be associated with an adverse outcome. In contrast, a prenatal history of mild or self-resolving hydronephrosis in a patient later presenting with intermittent dilatation, raises the suspicion of associated intrinsic PUJ obstruction, as it is associated with a higher risk of failure. CONCLUSION: With a long postoperative follow-up, the robotic-assisted or laparoscopic vascular hitch procedure has been successful in treating a selected group of children with obstructive LPCV, and represents a safe and reliable alternative to standard dismembered pyeloplasty in the absence of intrinsic PUJO suspected on prenatal US. PMID- 26139160 TI - Association of BMI and pediatric urologic postoperative events: Results from pediatric NSQIP. AB - BACKGROUND: Elevated body mass index (BMI) is a well-known risk factor for perioperative complications in adults, but has not been investigated in children undergoing urologic procedures. Given the low rate of complications associated with urologic surgery, a large sample is required for their characterization, but BMI is frequently not available in administrative databases. Here we report results from the first nationally based, prospectively assembled cohort analyzed with respect to the association of BMI with 30-day postoperative events for pediatric urologic procedures. OBJECTIVE: To determine the association of elevated BMI with overall 30-day postoperative events and wound complications in a large national sample of children undergoing urologic procedures. STUDY DESIGN: We queried the 2012 Pediatric National Surgical Quality Improvement Program database (NSQIP), defining obesity as a BMI above the 95th percentile and overweight above the 85th percentile, per CDC definitions. We used BMI <85th percentile as a referent group. Complications were collected within 30 days of the procedure. Comorbidity was classified on a linear scale using a validated pediatric-specific comorbidity score, and procedures were classified as genital, abdominal without bowel involvement, or abdominal with bowel involvement. Univariate and multivariate logistic models were used to test significance of associations. RESULTS: 2871 patients aged 2-18 years were analyzed. Of these, 420 (14.6%) were overweight and 440 (15.3%) were obese. A summary of 30-day events and complications is shown in the structured abstract table. On multivariate analysis adjusting for age, gender, class of procedure, and comorbidity, BMI remained a significant risk factor for 30-day events when comparing BMI >=85th percentile to BMI <85th percentile (OR 1.36, 95% CI 1.03-1.8, p = 0.035). An exploratory subgroup analysis examining the rate of wound complications demonstrated an odds ratio of 2.36 (95% CI 1.28-4.35, p = 0.006) for BMI >85th percentile on multivariate analysis. DISCUSSION: Overweight/obese status increased the odds of overall complications by 36%, and of wound complications by 140%. In adults there is a known profound effect of body composition on wound complications, but in children this association is less clear, and has not been studied in the pediatric urologic literature on a large scale. The mechanisms linking BMI to pediatric postoperative complications are unclear, but cytokine mechanisms or changes in the response to inflammation have been postulated. Limitations of this study include restriction to those urologic procedures included in ACS-NSQIPP and sorted into broad general categories. We did not control for secondary procedures. BMI/BMI percentile may not be appropriate measures of body composition in patients with atypical body habitus or proportions (e.g. myelomeningocele). CONCLUSION: BMI in the pediatric NSQIP urologic population was found to be associated with overall complication after adjustment for case type and preoperative comorbidity in a large national sample assembled for assessment of perioperative outcomes. An exploratory analysis uncovered more than two-fold increase in odds of wound complication in obese/overweight patients compared with a normal weight referent population. These results may be useful in preoperative counseling patients regarding perioperative risk. PMID- 26139162 TI - Benchmarking two-photon absorption cross sections: performance of CC2 and CAM B3LYP. AB - We investigate the performance of CC2 and TDDFT/CAM-B3LYP for the calculation of two-photon absorption (TPA) strengths and cross sections and contrast our results to a recent coupled cluster equation-of-motion (EOM-EE-CCSD) benchmark study [K. D. Nanda and A. I. Krylov, J. Chem. Phys., 2015, 142, 064118]. In particular, we investigate whether CC2 TPA strengths are significantly overestimated compared to higher-level coupled-cluster calculations for fluorescent protein chromophores. Our conclusion is that CC2 TPA strengths are only slightly overestimated compared to the reference EOM-EE-CCSD results and that previously published overestimated cross sections are a result of inconsistencies in the conversion of the TPA strengths to macroscopic units. TDDFT/CAM-B3LYP TPA strengths, on the other hand, are found to be 1.5 to 3 times smaller than the coupled-cluster reference for the molecular systems considered. The unsatisfactory performance of TDDFT/CAM-B3LYP can be linked to an underestimation of excited-state dipole moments predicted by TDDFT/CAM-B3LYP. PMID- 26139161 TI - Malondialdehyde-Modified LDL IgG Antibody Levels and Indices of Cardiac Function in Valvular Heart and Coronary Artery Disease Patients. AB - OBJECTIVE: To compare the changes in anti-malondialdehyde-modified low-density lipoprotein (MDA-LDL) IgG levels among patients undergoing off-pump and on-pump coronary artery bypass grafting (CABG) or valvuloplasty. SUBJECTS AND METHODS: A total of 38, 39 and 34 patients who underwent off-pump CABG, on-pump CABG and valvuloplasty, respectively, were enrolled in this study. Serum anti-MDA-LDL IgG values were measured 24 h before and after the operative procedures and at discharge. Echocardiography was also done before surgery and before discharge. The results were compared with values from 50 healthy controls. RESULTS: In all patients, a reduction in antibody titers was observed post-operatively. However, the decrease was significant only in the off-pump CABG - before surgery: 42.33 (25.83-58.51), after surgery: 30.86 (16.36-51.33) and at discharge: 10.96 (6.82 23.57; p = 0.027). There was a significant positive association between anti-MDA LDL IgG levels and ejection fraction (r = 0.248, p = 0.036) and a negative association with E/E', a marker of pulmonary capillary wedge pressure, in the coronary patients (r = -0.345, p = 0.012), but no significant associations were found in patients with valvular heart disease. CONCLUSIONS: Serum anti-MDA-LDL IgG levels were associated with cardiac function indices in coronary patients undergoing CABG. PMID- 26139163 TI - Work or welfare after cancer? Explorations of identity and stigma. AB - With increasing numbers of people living with cancer, a greater focus is required on the social consequences of the disease. This article explores the connections between cancer and employment and the constraints imposed by ill health and wider structural conditions. Narrative data from 23 people of working age with cancer in north-east England collected longitudinally over 16 months highlight the impact of financial strain caused by temporary or permanent interruption to employment, and the positive benefits of an upstream welfare rights intervention in enabling participants to claim benefit entitlements and boost incomes. Returning to work, for those who were able, helped repair the disruption caused by the illness. For those unable to work, reliance on welfare benefits, while necessary, conferred a stigmatised identity that compounded the disruption wrought by cancer. While stigma occurs at the individual level, the structural dimensions of stigma need to be acknowledged in order to analyse the forces that cause, maintain and perpetuate the stigma associated with claiming welfare while ill. We conclude that current UK policies and welfare reforms to reduce sickness related welfare claims will lead to greater hardship during periods of ill health and increase inequalities. PMID- 26139164 TI - High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes. AB - Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5 mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited. PMID- 26139166 TI - Acute Toxicity Prediction in Multiple Species by Leveraging Mechanistic ToxCast Mitochondrial Inhibition Data and Simulation of Oral Bioavailability. AB - There is great interest in assessing the in vivo toxicity of chemicals using nonanimal alternatives. However, acute mammalian toxicity is not adequately predicted by current in silico or in vitro approaches. Mechanisms of acute toxicity are likely conserved across invertebrate, aquatic, and mammalian species, suggesting that dose-response concordance would be high and in vitro mechanistic data could predict responses in multiple species under conditions of similar bioavailability. We tested this hypothesis by comparing acute toxicity between rat, daphnia, and fish and by comparing their respective acute data to inhibition of mitochondria membrane potential (MMP) using U.S. Environmental Protection Agency ToxCast in vitro high-throughput screening data. Logarithmic scatter plots of acute toxicity data showed a clear relationship between fish, daphnia, and intravenous rat but not oral rat data. Similar plots versus MMP showed a well-delineated upper boundary for fish, daphnia, and intravenous data but were scattered without an upper boundary for rat oral data. Adjustments of acute oral rat toxicity values by simulating fractional absorption and CYP-based metabolism as well as removing compounds with hydrolyzable linkages or flagged as substrates for glucuronidation delineated an upper boundary for rat oral toxicity versus MMP. Mitochondrial inhibition at low concentrations predicted highly acutely toxic chemicals for fish and daphnia but not the rat where toxicity was often attenuated. This use of a single high-throughput screening assay to predict acute toxicity in multiple species represents a milestone and highlights the promise of such approaches but also the need for refined tools to address systemic bioavailability and the impact of limited absorption and first pass metabolism. PMID- 26139165 TI - Ah Receptor Signaling Controls the Expression of Cardiac Development and Homeostasis Genes. AB - Congenital heart disease (CHD) is the most common congenital abnormality and one of the leading causes of newborn death throughout the world. Despite much emerging scientific information, the precise etiology of this disease remains elusive. Here, we show that the aryl hydrocarbon receptor (AHR) regulates the expression of crucial cardiogenesis genes and that interference with endogenous AHR functions, either by gene ablation or by agonist exposure during early development, causes overlapping structural and functional cardiac abnormalities that lead to altered fetal heart physiology, including higher heart rates, right and left ventricle dilation, higher stroke volume, and reduced ejection fraction. With striking similarity between AHR knockout (Ahr(-/-)) and agonist-exposed wild type (Ahr(+/+)) embryos, in utero disruption of endogenous AHR functions converge into dysregulation of molecular mechanisms needed for attainment and maintenance of cardiac differentiation, including the pivotal signals regulated by the cardiogenic transcription factor NKH2.5, energy balance via oxidative phosphorylation and TCA cycle and global mitochondrial function and homeostasis. Our findings suggest that AHR signaling in the developing mammalian heart is central to the regulation of pathways crucial for cellular metabolism, cardiogenesis, and cardiac function, which are potential targets of environmental factors associated with CHD. PMID- 26139167 TI - We are very much like each other. PMID- 26139168 TI - Coronary sinus dilatation as a sign of right ventricular dysfunction in patients with heart failure. PMID- 26139169 TI - Electrocardiographic findings in correlation to cardiac magnetic resonance imaging patterns for isolated ventricular non-compaction patients. PMID- 26139170 TI - Percutaneous and surgical removal of two cases of embolized totally implantable venous access devices that were implanted a long time ago. PMID- 26139171 TI - Coil embolization of iatrogenic coronary-pulmonary arterial fistula after heart transplantation. PMID- 26139172 TI - An arrhythmic episode after mercury exposure and successful treatment with chelation therapy: A case report. PMID- 26139173 TI - Short QT syndrome in a 14-year-old patient: The first pediatric case from Turkey. PMID- 26139174 TI - Iron overload and fragmented QRS in patients with Thalassemia major: Mechanisms, therapies, and new horizons. PMID- 26139175 TI - Apical transverse motion is associated with speckle-tracking radial dyssynchrony in patients with non-ischemic dilated cardiomyopathy. PMID- 26139176 TI - Could the data of home blood pressure monitoring be used to evaluate the risk of subclinical target organ damage in hypertensive patients? PMID- 26139178 TI - A rare indication for Senning operation: Isolated ventricular inversion and ventricular septal defect. PMID- 26139179 TI - Mycobacterium fortuitum thoracic empyema: A case report and review of the literature. AB - Mycobacterium fortuitum is a rapidly growing nontuberculous mycobacterium. This microorganism is an uncommon etiological agent of lung lesions; among lung lesions caused by M. fortuitum, thoracic empyema is particularly rare. A 61-year old man who had been treated for chronic hypercapnic respiratory failure with noninvasive ventilation was admitted because of breathing difficulty and was found to have M. fortuitum thoracic empyema. He improved after the administration of amikacin, imipenem/cilastatin, and clarithromycin following sulfamethoxazole/trimethoprim and clarithromycin. This is the first report of M. fortuitum thoracic empyema in a patient without human immunodeficiency virus infection. The thoracic empyema may have developed via a pulmonary fistula in this case. This case highlights the fact that we must be aware of the possibility of M. fortuitum thoracic empyema, especially in patients with M. fortuitum lung infection and treatment with noninvasive ventilation. Multidrug therapy may be effective and important to the resolution of M. fortuitum thoracic empyema. PMID- 26139180 TI - Dysphagia after cervical spine fusion caused by migration of the prosthetic material. PMID- 26139181 TI - Normothermic perfusion machine in liver transplant with cardiac death donor grafts. AB - The increasing difference between the number of patients in waiting lists for liver transplantation and the number of available donors has generated a great interest in the use of non-ideal organs, like grafts obtained from cardiac death donors (DCD). However, the extreme sensibility to ischemia of these livers results in a low utilization rate and a high percentage of post-transplant complications and re-transplantation. Normothermic perfusion machines (NMP) emerged as an alternative that tries to maintain the viability of the organ and even to improve its function. This review focuses on current results of DCD liver transplantation and on the role that NMP may have in this field. PMID- 26139182 TI - Cellular Proteins Act as Bridge Between 5' and 3' Ends of the Coxsackievirus B3 Mediating Genome Circularization During RNA Translation. AB - The positive single-stranded RNA genome of the Coxsackievirus B3 (CVB3) contains a 5' untranslated region (UTR) which hosts the internal ribosome entry site (IRES) element that governs cap-independent translation initiation and a polyadenylated 3' UTR which is required for stimulating the IRES activity. Viral RNA genomes could circularize to regulate initiation of translation and RNA synthesis at 5' and 3' ends. Interactions could either take place by direct RNA RNA contacts, through cellular protein bridges mediating RNA circularization or both. Accordingly, we aimed to assess the nature of molecular interactions between these two regions and to evaluate cellular factors required for mRNA 3' end-mediated stimulation of CVB3 IRES-driven translation. By gel shift assays, we have showed that combining, in vitro, 5' and 3' UTR fragments had no discernible effect on the structures of RNAs, arguing against the presence of specific canonical RNA-RNA cyclization sequences between these two regions. Competitive UV crosslinking assays using BHK-21 cell extract showed common cellular proteins eIF3b, PTB, and La binding to both 5'- and 3' end RNAs. PCBP 1-2 and PABP were shown to bind, respectively, to 5' and 3' UTR probes. Taking together, these data suggest that CVB3 5'-3' end bridging occurs through 5' UTR-protein-protein-3' UTR interactions and not through RNA-RNA direct contact. The dual involvement of the 3' and 5' UTRs in controlling viral translation and RNA synthesis highlights the relevance of these regions in the infectious virus life cycle, making them suitable candidates for targeted CVB3 antiviral therapy. PMID- 26139183 TI - Introduced birds incompletely replace seed dispersal by a native frugivore. AB - The widespread loss of native species and the introduction of non-native species has important consequences for island ecosystems. Non-native species may or may not functionally replace the role of native species in ecological processes such as seed dispersal. Although the majority of Hawaii's native plants require bird mediated seed dispersal, only one native frugivore, Omao (Myadestes obscurus), persists in sufficient numbers to fill this functional role. Omao are restricted to less than half their original range, but two introduced frugivores are abundant throughout Hawaii. Given large-scale extinctions on islands, it is important to understand whether introduced birds serve as functional replacements or whether the absence of native frugivores alters plant communities. To assess seed dispersal by native and introduced birds, seed rain, vegetation characteristics, bird diet, density and habitat use were measured at three sites with Omao and three sites without Omao on Hawaii Island. The diet of native and introduced birds overlapped substantially, but Omao dispersed a variety of native species (n = 6) relatively evenly. In contrast, introduced birds dispersed an invasive species and fewer native species (n = 4), and >90 % of seeds dispersed by introduced birds were from two ubiquitous small-seeded species. Seed rain was significantly greater and more species rich at sites with Omao. These findings suggest that patterns of seed dispersal are altered following the local extinction of a native island frugivore. To more directly evaluate the relative roles of native and introduced frugivores in ecological processes, future studies could include reintroducing Omao to a suitable habitat within its historic range, or novel introductions to nearby islands where closely related species are now extinct. In an era of widespread extinction and invasion of island ecosystems, understanding the consequences of novel animal assemblages for processes like seed dispersal will be critical for maintaining diverse and self-regenerating plant communities. PMID- 26139184 TI - Distribution of three congeneric shrub species along an aridity gradient is related to seed germination and seedling emergence. AB - Environmental tolerance of a species has been shown to correlate positively with its geographical range. On the Ordos Plateau, three Caragana species are distributed sequentially along the precipitation gradient. We hypothesized that this geographical distribution pattern is related to environmental tolerances of the three Caragana species during seed germination and seedling emergence stages. To test this hypothesis, we examined seed germination under different temperature, light and water potentials, and monitored seedling emergence for seeds buried at eight sand depths and given different amounts of water. Seeds of C. korshinskii germinated to high percentages at 5 : 15 to 25 : 35 degrees C in both light and darkness, while those of C. intermedia and C. microphylla did so only at 15 : 25 and 25 : 35 degrees C, respectively. Nearly 30 % of the C. korshinskii seeds germinated at -1.4 MPa at 20 and 25 degrees C, while no seeds of the other two species did so. Under the same treatments, seedling emergence percentages of C. korshinskii were higher than those of the other two species. The rank order of tolerance to drought and sand burial of the three species is C. korshinskii > C. intermedia > C. microphylla. The amount of precipitation and sand burial depth appear to be the main selective forces responsible for the geographical distribution of these species. PMID- 26139185 TI - Charge-order domain walls with enhanced conductivity in a layered manganite. AB - Interfaces and boundaries in condensed-matter systems often have electronic properties distinct from the bulk material and thus have become a topic of both fundamental scientific interest and technological importance. Here we identify, using microwave impedance microscopy, enhanced conductivity of charge-order domain walls in the layered manganite Pr(Sr0.1Ca0.9)2Mn2O7. We obtain a complete mesoscopic map of surface topography, crystalline orientation and electronic phase, and visualize the thermal phase transition between two charge-ordered phases. In both phases, charge-order domains occur with domain walls showing enhanced conductivity likely due to local lifting of the charge order. Finite element analysis shows that the resolved domain walls can be as narrow as few nanometres. The domain walls are stabilized by structural twins and have a strong history dependence, suggesting that they may be manipulated to create novel devices. PMID- 26139186 TI - Feedlot Vaccination: Does It Really Matter? AB - The practice of vaccination has been used for more than 200 years and is an important component of livestock preventive medicine programs. The goal of vaccination is to stimulate an immune response in an individual that will protect that individual from disease or reduce the clinical signs in that individual. Vaccination applied to a population has a similar goal, as well as decreasing or preventing spread within a population. Commercial vaccines are evaluated for efficacy and safety, and the proper application of these products to varied cattle populations requires knowledge of risk factors and production system factors. PMID- 26139187 TI - Management of Preconditioned Calves and Impacts of Preconditioning. AB - When studying the practice of preconditioning (PC) calves, many factors need to be examined to determine if cow-calf producers should make this investment. Factors such as average daily gain, feed efficiency, available labor, length of the PC period, genetics, and marketing options must be analyzed. The health sales price advantage is an additional benefit in producing and selling PC calves but not the sole determinant of PC's financially feasibility. Studies show that a substantial advantage of PC is the selling of additional pounds at a cost of gain well below the marginal return of producing those additional pounds. PMID- 26139188 TI - Management of Pregnant Heifers in the Feedlot. AB - Pregnant heifers in the feedlot pose many economic and management issues to the producer. Heifers that enter the feedlot pregnant will have increased costs associated with them regardless of the management strategy implemented. It is imperative that practitioners be aware of management concerns associated with pregnant heifers in order to provide sound recommendations for their clients. The purpose of this article is to provide the bovine practitioner with a summary of current literature and present common options for managing pregnant heifers in a feedlot setting. PMID- 26139189 TI - Current Status of Parasite Control at the Feed Yard. AB - Fly and louse infestations are readily discerned and remedied in feedlot cattle. Tapeworm and fluke infections are accepted as probable but, given the lack of anthelmintics with realistic efficacy against these infections, these helminths are allowed to persist without treatment. Nematode infections are considered ubiquitous with cattle coming from pasture and are targeted with a macrocyclic lactone, usually in combination with a benzimidazole. Populations of nematodes seem to be effectively controlled by a combination of anthelmintic treatment, animal resistance and resilience, lack of reinfection, and diet. PMID- 26139190 TI - Management of Cattle Exposed to Adverse Environmental Conditions. AB - During periods of adverse weather, optimum conditions for animal comfort and performance are compromised. Use of alternative supplementation programs need to be considered for livestock challenged by adverse environmental conditions. Use of additional water for consumption and cooling, shade, and/or alternative management strategies need to be considered to help livestock cope with heat stress. For animals reared outside during winter, strategies that increase animal space and environmental buffers need to be used to minimize effects of mud, wet conditions, and windchill. There are ample opportunities for livestock producers to enhance animal welfare and minimize the impact of environmental stress. PMID- 26139191 TI - Animal Health Equipment Management. AB - Proper health equipment management requires significant attention to detail. Establishing and following protocols during processing (eg, cleaning and disinfecting equipment at the end of the work day) is required to ensure a safe product that is free of defects and residues. Overall cleanliness of equipment and facilities is important not only from a food safety standpoint but many view these as an overall indicator of attention to detail in the entire production system. Ensuring that needles are changed, implant guns are managed properly, vaccine is handled in an acceptable manner, and that proper chute operation occurs is essential. PMID- 26139192 TI - Beef Quality Assurance in Feedlots. AB - This article discusses the Beef Quality Assurance (BQA) program, which was created by beef producers and veterinarians. The program has evolved from antibiotic residue avoidance to include animal handling, cattle comfort, food safety, and much more. It provides guidance to producers and veterinarians on best management practices and allows the beef industry to be transparent about the practices used. Veterinarians are key to helping producers implement BQA in their beef operations. PMID- 26139193 TI - Nutrition of Newly Received Feedlot Cattle. AB - The stress of transition from pasture to the feedlot environment creates unique and variable nutritional challenges. The factors that are used to assign a risk category for the likelihood of developing bovine respiratory disease include time in transit from their origin, which is likely to be highly correlated with the amount of time away from quality feed and water. A high risk of developing respiratory disease is likely to correlate well with the animals' suppressed appetite immediately after arrival. This article discusses 2 distinctive categories of feeder animals (high-risk calves and yearlings) and their nutritional needs. PMID- 26139194 TI - Indoor Confined Feedlots. AB - Indoor confined feedlots offer advantages that make them desirable in northern climates where high rainfall and snowfall occur. These facilities increase the risk of certain health risks, including lameness and tail injuries. Closed confinement can also facilitate the rapid spread of infectious disease. Veterinarians can help to manage these health risks by implementing management practices to reduce their occurrence. PMID- 26139195 TI - Feedlot Pharmaceutical Documentation: Protocols, Prescriptions, and Veterinary Feed Directives. AB - The days of oral treatment instructions and loosely associated authorizations for the use of drugs in food animals are gone. Treatment protocols should include case definitions for treatment eligibility, detailed regimens, case definitions for treatment success and failure, directions for animal disposition, and mechanisms to prevent animals entering the food chain with violative residues. Prescriptions and veterinary feed directives (VFDs) will soon be necessary for almost all uses of antimicrobials in food animals. Although VFDs have a regulatory format, prescriptions may vary, but there are basic inclusions that should be present in any prescription. PMID- 26139196 TI - Managing Feeder Cattle Health the First 30 Days on Feed. PMID- 26139197 TI - Acute pulmonary edema and pregnancy: a challenging case. PMID- 26139198 TI - Efficient Synthesis of Single-Chain Globules Mimicking the Morphology and Polymerase Activity of Metalloenzymes. AB - Endowing unimolecular soft nanoobjects with biomimetic functions is attracting significant interest in the emerging field of single-chain technology. Inspired by the compartmentalized structure and polymerase activity of metalloenzymes, copper-containing compact nanoglobules have been designed, synthesized, and characterized endowed with metalloenzyme mimicking characteristics toward controlled synthesis of water-soluble polymers and thermoresponsive hydrogels. When compared to metalloenzymes, artificial nanoobjects endowed with metalloenzyme mimicking characteristics offer increased stability against thermal changes and reduced degradability by hydrolytic enzymes. PMID- 26139199 TI - Concurrent Hepsin overexpression and adenomatous polyposis coli deletion causes invasive prostate carcinoma in mice. AB - BACKGROUND: A clinical need to better categorize patients with prostate cancer exists. The Wnt/beta-catenin signaling pathway plays important roles in human prostate cancer progression. Deletion of the endogenous Wnt antagonist adenomatous polyposis coli (Apc) in mice causes high grade prostate intraepithelial neoplasia, widely thought to be the precursor to prostate cancer. However, no metastasis occurrs in this model. New mouse models are needed to determine molecular causes of tumorigenesis, progression, and metastasis. METHODS: To determine whether the overexpression of the prostate oncogene Hepsin could cause prostate cancer progression, we crossed a prostate-specific Hepsin overexpression model to a prostate-specific Apc-deletion model and classified the observed phenotype. RESULTS: When Apc was deleted and Hepsin overexpressed concurrently, mice displayed invasive carcinoma, with loss of membrane characteristics and increase of fibrosis. These tumors had both luminal and basaloid characteristics. Though no metastasis was observed, there was evidence of adenomas and lung necrosis, inflammation, and chronic hemorrhage. CONCLUSIONS: This work indicates that the Wnt/beta-catenin pathway and the Hepsin pathway act in concert to promote prostate cancer progression. Both of these pathways are up regulated in human prostate cancer and could represent chemotherapeutic targets. PMID- 26139200 TI - Evaluation of bedside pulmonary function in the neonate: From the past to the future. AB - Pulmonary function testing and monitoring plays an important role in the respiratory management of neonates. A noninvasive and complete bedside evaluation of the respiratory status is especially useful in critically ill neonates to assess disease severity and resolution and the response to pharmacological interventions as well as to guide mechanical respiratory support. Besides traditional tools to assess pulmonary gas exchage such as arterial or transcutaenous blood gas analysis, pulse oximetry, and capnography, additional valuable information about global lung function is provided through measurement of pulmonary mechanics and volumes. This has now been aided by commercially available computerized pulmonary function testing systems, respiratory monitors, and modern ventilators with integrated pulmonary function readouts. In an attempt to apply easy-to-use pulmonary function testing methods which do not interfere with the infants airflow, other tools have been developed such as respiratory inductance plethysmography, and more recently, electromagnetic and optoelectronic plethysmography, electrical impedance tomography, and electrical impedance segmentography. These alternative technologies allow not only global, but also regional and dynamic evaluations of lung ventilation. Although these methods have proven their usefulness for research applications, they are not yet broadly used in a routine clinical setting. This review will give a historical and clinical overview of different bedside methods to assess and monitor pulmonary function and evaluate the potential clinical usefulness of such methods with an outlook into future directions in neonatal respiratory diagnostics. PMID- 26139201 TI - Reply to "Comment on 'The Mechanism of Pyrolysis of Benzyl Azide: Spectroscopic Evidence for Benzemethanimine Formation'". PMID- 26139202 TI - Efficacy and safety evaluation of a combination of iguratimod and methotrexate therapy for active rheumatoid arthritis patients: a randomized controlled trial. AB - This study aimed to investigate the efficacy and safety of iguratimod (T-614) in combination with methotrexate (MTX) for active rheumatoid arthritis (RA) patients. Sixty active RA patients were enrolled according to the 2010 American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) classification criteria, and were randomized into MTX + T-614 group and MTX group. T-614 was orally administered at a dosage of 50 mg/day (25 mg twice daily) for 24 weeks. MTX was orally administered to RA patients at a stable weekly dosage of 10 mg/week for the first 4 weeks and subsequent 12.5 mg/week for the later 20 weeks. Clinical features at baseline and efficacy endpoints of the ACR 20 % response (ACR20), ACR50, ACR70, and adverse events at 24 weeks were evaluated, respectively. After 24 weeks of treatment, clinical features at baseline, including counts for tender joints and swelling joints, visual analog scale for pain, patient's and physician's global assessment, erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, health assessment questionnaire, simplified disease activity index, and ACR50 in the MTX + T-614 group, showed statistically significant differences comparing with the MTX group (P < 0.05). There was no significant increase in adverse events in the MTX + T-614 group comparing with the MTX group (P > 0.05). The combination of MTX and T-614 therapy appeared to have a good efficacy and safety for active RA and was superior to MTX-alone therapy after 24 weeks of treatment. PMID- 26139203 TI - Evaluation of the Treatment of Congenital Penile Curvature Including Psychosexual Assessment. AB - INTRODUCTION: Penile corporoplasty is a well-established treatment method of congenital penile deviation (CPD). Anatomical results are good with only slight differences between surgical procedures used. The disease however has huge influence on young male quality of life. This issue is not well analyzed in the literature. AIM: The aim of the study was to evaluate quality of life of the patients affected with CPD before and after the surgical treatment METHODS: Study population consisted of 107 patients with CPD referred for surgical management. Patients were evaluated with not only clinical assessment, but also by four questionnaires measuring various aspects of quality of life. They were: Short Form Medical Outcomes, Sexual Quality of Life Questionnaire for Man, Beck Depression Inventory, and International Index of Erectile Function. RESULTS: Quality of life measurements showed deep decrease in the general quality of life, sexual performance, depression scale, as well as in physical and mental health in men with CPD. All these parameters were restored to normal after the successful surgical treatment with any method. CONCLUSION: CPD deeply decreases the quality of life of the affected men in many aspects. Surgical treatment is able to repair the anatomical deformity and as well as significantly restore the patients' psychosocial well-being. PMID- 26139204 TI - Myocardial Infarction after Ozone Therapy: Is Ozone Therapy Dr. Jekyll or Mr. Hyde? AB - We discuss the case of a 46-year-old male patient presenting to the emergency department with acute inferior myocardial infarction. Coronary angiography demonstrated a vasospasm of the left main coronary artery and proximal segment of the left anterior descending artery. Furthermore, a thrombotic total occlusion was ascertained in the right coronary artery. The vasospasm in the left main and left anterior descending artery disappeared after nitrate administration. We successfully implanted a stent to the thrombotic occlusion in the right coronary artery after predilatation. On detailed questioning, the patient stated that ozonated autohemotherapy had been applied that morning in a private clinic for the revitalization and regeneration of tissues. The patient did not have any traditional atherosclerotic risk factors. He denied any history of cardiac complaint. Factor V Leiden, prothrombin 20210 and MTHFR a1298c and c677t mutations were investigated and found to be negative except for MTHFR a1298c, which was a heterozygote. The levels of antithrombin III, homocysteine and protein C and S were all within normal ranges. Ozone as a medical therapy has been used in many medical conditions; unfortunately, however, like every other therapy, ozone therapy has side effects. The literature concerning ozone therapy supports possible strong vasoconstrictor and prothrombotic effects of ozone therapy, further supporting our suggestion that ozone can lead to acute coronary syndromes in human beings. In conclusion, to our knowledge, our case report reveals a possible complication of ozone therapy that has never been reported before. We think that this article will raise the awareness of the possibility of thrombotic complications after ozonated autohemotherapy. (c) 2015 S. Karger AG, Basel. PMID- 26139205 TI - Risk factors for incident HSV-2 infections among a prospective cohort of HIV-1 discordant couples in China. AB - OBJECTIVES: Identification of risk factors is essential for developing herpes simplex virus type 2 (HSV-2) prevention interventions that could also reduce HIV 1 transmission, particularly among HIV-1-discordant couples. METHODS: A prospective cohort study was conducted among HIV-1-discordant couples from June 2009 to March 2011 in Yunnan province, China. 413 HIV-1-infected partners and 517 HIV-1-uninfected partners who were HSV-2 seronegative or equivocal at enrolment and who had a study partner completing the baseline survey and HSV-2 testing were included in the analysis. RESULTS: HSV-2 incidence was 2.9 per 100 person-years (PY) for HIV-1-infected partners and 4.5 per 100 PY for HIV-1-uninfected partners. At least 36% of incident HSV-2 infections were from outside sexual partner. Among HIV-1-infected partners, multivariate analysis indicated that HSV 2 incidence was significantly higher among those with baseline equivocal HSV-2 result, having an initially HSV-2 seropositive or equivocal partner, reporting no sex with study partner and initiating antiretroviral therapy (ART) during follow up. Among HIV-1-uninfected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those having an initially HSV-2 seropositive partner and reporting sex with study partner >=5 times/month, but was lower among those having a partner with baseline CD4(+) count >=350 cells/MUL. CONCLUSIONS: Our findings underscore the importance of developing prevention and intervention programmes to reduce HSV-2 transmission among this population. The relationship between ART initiation and HSV-2 seroconversion requires further investigation. PMID- 26139206 TI - Human rights and HIV interventions in Chinese labour camps. PMID- 26139207 TI - Isolation of Haemophilus influenzae and Haemophilus parainfluenzae in urethral exudates from men with acute urethritis: a descriptive study of 52 cases. AB - OBJECTIVES: To describe the clinical characteristics and therapeutic outcomes from male patients diagnosed of Haemophilus spp urethritis. METHODS: A chart review of patients who presented to our hospital from January 2013 to December 2014 with symptoms of acute urethritis in which Haemophilus spp was isolated in their urethral samples was performed. RESULTS: Haemophilus spp was isolated in 52 out of 413 urethral samples (12.6%) received in our laboratory from patients with symptoms of acute urethritis during the study period. Seven cases corresponded to Haemophilus influenzae and 45 cases to Haemophilus parainfluenzae. The most common clinical presentation was mucopurulent urethral discharge (71%). Eight per cent were HIV-infected patients, and 60% were men who have sex with men. Haemophilus spp was isolated as a single pathogen in 6.8% (28 of 413) of cases. Seventeen per cent of Haemophilus spp were beta-lactamase producers. All patients reported having practiced unprotected insertive oral sex the month before consultation, and five of them denied having had another sexual contact apart from this exposure. In all cases in which follow-up was available, empirical treatment achieved a complete clinical resolution. CONCLUSIONS: Haemophilus spp was considered a pathogen in at least 6.8% of the patients from the evaluated area. It affected men regardless their sexual orientation or HIV status. Unprotected oral sex could play a role in its transmission. The limitations of the study (small sample size and lack of a representative control group) do not allow to prove the true pathogenic role of Haemophilus spp in acute urethritis. PMID- 26139209 TI - cAMP signaling in cortisol-producing adrenal adenoma. AB - The cAMP signaling pathway is one of the major players in the regulation of growth and hormonal secretion in adrenocortical cells. Although its role in the pathogenesis of adrenocortical hyperplasia associated with Cushing's syndrome has been clarified, a clear involvement of the cAMP signaling pathway and of one of its major downstream effectors, the protein kinase A (PKA), in sporadic adrenocortical adenomas remained elusive until recently. During the last year, a report by our group and three additional independent groups showed that somatic mutations of PRKACA, the gene coding for the catalytic subunit alpha of PKA, are a common genetic alteration in patients with Cushing's syndrome due to adrenal adenomas, occurring in 35-65% of the patients. In vitro studies revealed that those mutations are able to disrupt the association between catalytic and regulatory subunits of PKA, leading to a cAMP-independent activity of the enzyme. Despite somatic PRKACA mutations being a common finding in patients with clinically manifest Cushing's syndrome, the pathogenesis of adrenocortical adenomas associated with subclinical hypercortisolism seems to rely on a different molecular background. In this review, the role of cAMP/PKA signaling in the regulation of adrenocortical cell function and its alterations in cortisol producing adrenocortical adenomas will be summarized, with particular focus on recent developments. PMID- 26139208 TI - Disclosure of HSV-2 serological test results in the context of an adolescent HIV prevention trial in Kenya. AB - OBJECTIVES: Herpes simplex virus type 2 (HSV-2) biomarkers are often used in adolescent sub-Saharan HIV prevention studies, but evaluations of test performance and disclosure outcomes are rare in the published literature. Therefore, we investigated the proportion of ELISA-positive and indeterminate samples confirmed by western blot (WB), the psychosocial response to disclosure and whether reports of sexual behaviour and HSV-2 symptoms are consistent with WB confirmatory results among adolescent orphans in Kenya. METHODS: In 2011, 837 Kenyan orphan youth in grades 7 and 8 enrolled in an HIV prevention clinical trial with HSV-2 biomarker outcomes. We used a modified algorithm for the Kalon HSV-2 ELISA to improve specificity; positive and indeterminate results were WB tested. We developed culturally sensitive protocols for disclosing positive results, and documented psychosocial responses, reports of sexual contact and HSV 2 symptoms. RESULTS: 28 adolescents (3.3%) were identified as HSV-2 seropositive, six as indeterminate. Of these, 22 positive and all indeterminates were WB tested; 20 and 5, respectively, were confirmed positive. Most youth reported moderate brief stress after disclosure; 22% reported longer and more severe distress. Boys were more likely to be in the latter category. Self-reported virginity was highly inconsistent with WB-confirmed positives. CONCLUSIONS: The higher than manufacturer's cut-off for Kalon ELISA modestly reduced the rate of false-positive test results, but also increased false negatives. Investigators should consider the risk:benefit ratio in deciding whether or not to disclose HSV 2 results to adolescent participants under specific field conditions. TRIAL REGISTRATION NUMBER: NCT01501864. PMID- 26139210 TI - BclI glucocorticoid receptor polymorphism in relation to cardiovascular variables: the Hoorn and CODAM studies. AB - OBJECTIVE: Excess glucocorticoids are known to cause hypertension and cardiovascular disease (CVD). The BclI glucocorticoid receptor (GR) polymorphism increases glucocorticoid sensitivity and is associated with adverse metabolic effects. Previous studies investigating cardiovascular implications have shown inconsistent results. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with blood pressure, atherosclerosis, low-grade inflammation, endothelial dysfunction, and prevalent CVD. DESIGN: Observational cohort study, combining two cohort studies designed to investigate genetic and metabolic determinants of CVD. METHODS: We genotyped 1228 individuals (aged 64.7 years+/-8.5) from the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study and Hoorn study for the BclI polymorphism. We measured blood pressure, ankle-brachial index (ABI), and carotid intima-media thickness (cIMT). Low-grade inflammation and endothelial dysfunction scores were computed by averaging Z-scores of six low-grade inflammation markers and four endothelial dysfunction markers respectively. Prevalent CVD was assessed with questionnaires, hospital records, ECG, and ABI. RESULTS: Homozygous carriers (GG) had higher mean arterial pressure (103.8+/-12.4 mmHg vs 101.6+/-12.2 mmHg (mean+/-S.D.); P<0.05) compared with non-carriers (CC). Homozygous carriers had lower ABI compared with heterozygous carriers (CG) (1.08+/-0.13 vs 1.11+/-0.14; P<0.05). After adjustment for all covariates in the full model, the association with ABI was no longer significant. BclI was not associated with systolic blood pressure, cIMT, low-grade inflammation, endothelial dysfunction, and prevalent CVD. CONCLUSIONS: The BclI polymorphism of the GR gene may contribute to an unfavorable cardiovascular profile; however, the effects on cardiovascular variables appear to be limited and partly mediated by the metabolic phenotype exerted by BclI. PMID- 26139211 TI - Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF. AB - OBJECTIVE: About one out of two women with primary hypothyroidism has to increase the dosage of exogenous levothyroxine (L-T4) during pregnancy. Considering the detrimental impact of IVF on thyroid function, it has been claimed but not demonstrated that L-T4 dose adjustment may be more significant in hypothyroid women who become pregnant after IVF. DESIGN: Retrospective cohort study. METHODS: Hypothyroid-treated women who achieved a live birth through IVF were reviewed. Women could be included if thyroid function was well compensated with L-T4 before the IVF cycle (i.e., serum TSH <2.5 mIU/l and serum free T4 within the normal range). Serum TSH and dose adjustment were evaluated at five time points during pregnancy. The trimester ranges for serum TSH considered as reference to adjust L T4 therapy were 0.1-2.5 mIU/l for the first trimester, 0.2-3.0 mIU/l for the second trimester, and 0.3-3.0 mIU/l for the third trimester. RESULTS: Thirty eight women were selected. During the whole pregnancy 32 women (84%; 95% CI: 72 96%) required an increase in the dose of L-T4. In most cases (n=28), this occured within the first 5-7 weeks of gestation (74%, 95% CI: 58-85%). At 5-7 weeks of gestation, the median (interquartile range) increase of L-T4 dose for the whole cohort was 26% (0-50%). At 30-32 weeks, it was 33% (14-68%). In order to identify predictive factors of dose adjustment, we compared women who did (n=28) and did not (n=10) adjust L-T4 dosage at 5-7 weeks' gestation. Significant differences emerged for thyroid autoimmunity prevalence and for the distribution of hypothyroidism aetiology. CONCLUSIONS: The vast majority of hypothyroid-treated women who achieve pregnancy through IVF need an increase in the L-T4 dose during gestation. This requirement tends to occur very early during gestation. PMID- 26139212 TI - EFFECT OF NATIVITY AND DURATION OF RESIDENCE ON CHRONIC HEALTH CONDITIONS AMONG ASIAN IMMIGRANTS IN AUSTRALIA: A LONGITUDINAL INVESTIGATION. AB - This study examined the effect of Asian nativity and duration of residence in Australia on the odds of reporting a chronic health condition (cancer, respiratory problems, cardiovascular disease (CVD) and diabetes mellitus). Data were from waves 3, 7 and 9 of the Household Income and Labour Dynamics in Australia (HILDA) longitudinal survey, and multi-level group-mean-centred logistic regression models were used for the analysis. After covariate adjustment, Asian immigrants were less likely to report cancer and respiratory problem compared with native-born Australians. While there was no significant difference in reporting CVD, they were more likely to report diabetes than native born people. Asian immigrants maintained their health advantage with respect to cancer regardless of duration of residence. However, after 20 years of stay, Asian immigrants lost their earlier advantage and were not significantly different from native-born people in terms of reporting a respiratory problem. In contrast, Asian immigrants were not measurably different from native-born Australians in reporting diabetes if their length of stay in Australia was less than 20 years, but became disadvantaged after staying for 20 years or longer. There was no measurable difference in the odds of reporting CVD between Asian immigrants and native-born Australians for any duration of residence. On the whole this study found that health advantage, existence of healthy immigrant effect and subsequent erosion of it with increasing duration of residence among Asian immigrants depends upon the chronic health condition. PMID- 26139214 TI - The influence of central arterial compliance on cerebrovascular hemodynamics: insights from endurance training intervention. AB - Normally, central elastic arteries (e.g., aorta and common carotid artery) effectively buffer cardiac pulsation-induced flow/pressure fluctuations. With advancing age, arterial stiffening deteriorates this function and produces the greater cerebral hemodynamic pulsatility that impacts vulnerable brain tissue. It is well known that the buffering function of the central artery is improved by regular aerobic exercise, but the influence of endurance training on the pulsatile component of cerebral hemodynamics remains poorly understood. To characterize the functional role of the central artery at the heart-brain hemodynamic connection comprehensively, we assessed relations among the endurance training-induced changes in the left ventricle (LV), carotid arterial compliance, and cerebral hemodynamics. Thirteen collegiate tennis players (20 +/- 1 yr) underwent a 16-wk endurance training intervention designed for improving cardiovascular function. Expectedly, maximal oxygen uptake (Vo2peak), LV ejection velocity (via Doppler ultrasound), and the maximal rate of pressure increase of estimated aortic pressure waveform (via general transfer function) improved after the training intervention, whereas middle cerebral arterial (MCA) hemodynamics (via transcranial Doppler), such as mean and pulsatile flow velocities, remained unchanged. Carotid arterial compliance (via ultrasound and applanation tonometry) increased after the training intervention, and a larger increase in carotid arterial compliance was significantly associated with the greater attenuations of pulsatile MCA velocity (r = -0.621) normalized by mean MCA velocity. These results suggest that the training-induced improvement of carotid artery Windkessel function might offset the expected increase in the pulsatile component of cerebral perfusion induced by the enhanced LV systolic function. PMID- 26139213 TI - Cerebral blood velocity regulation during progressive blood loss compared with lower body negative pressure in humans. AB - Lower body negative pressure (LBNP) is often used to simulate blood loss in humans. It is unknown if cerebral blood flow responses to actual blood loss are analogous to simulated blood loss during LBNP. Nine healthy men were studied at baseline, during three levels of LBNP (5 min at -15, -30, and -45 mmHg), and during three levels of blood loss (333, 667, and 1,000 ml). LBNP and blood loss conditions were randomized. Intra-arterial mean arterial pressure (MAP) during LBNP was similar to that during blood loss (P >= 0.42). Central venous pressure (2.8 +/- 0.7 vs. 4.0 +/- 0.8, 1.2 +/- 0.6 vs. 3.5 +/- 0.8, and 0.2 +/- 0.9 vs. 2.1 +/- 0.9 mmHg for levels 1, 2, and 3, respectively, P <= 0.003) and stroke volume (71 +/- 4 vs. 80 +/- 3, 60 +/- 3 vs. 74 +/- 3, and 51 +/- 2 vs. 68 +/- 4 ml for levels 1, 2, and 3, respectively, P <= 0.002) were lower during LBNP than blood loss. Despite differences in central venous pressure, middle cerebral artery velocity (MCAv) and cerebrovascular conductance were similar between LBNP and blood loss at each level (MCAv at level 3: 62 +/- 6 vs. 66 +/- 5 cm/s, P = 0.37; cerebrovascular conductance at level 3: 0.72 +/- 0.05 vs. 0.73 +/- 0.05 cm.s(-1).mmHg(-1), P = 0.53). While the slope of the MAP-MCAv relationship was slightly different between LBNP and blood loss (0.41 +/- 0.03 and 0.66 +/- 0.04 cm.s(-1).mmHg(-1), respectively, P = 0.05), time domain gain between MAP and MCAv at maximal LBNP/blood loss (P = 0.23) and low-frequency MAP-mean MCAv transfer function coherence, gain, and phase were similar (P >= 0.10). Our results suggest that cerebral hemodynamic responses to LBNP to -45 mmHg and blood loss up to 1,000 ml follow a similar trajectory, and the arterial pressure-cerebral blood velocity relationship is not altered from baseline under these conditions. PMID- 26139215 TI - Sympathetic baroreflex gain in normotensive pregnant women. AB - Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 +/- 1 wk gestation, 31 +/- 1 yr, prepregnancy BMI: 23.5 +/- 0.9 kg/m(2)) and 11 nonpregnant controls (29 +/- 1 yr; BMI: 25.2 +/- 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 +/- 2 vs. 33 +/- 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 +/- 148 vs. 1,140 +/- 55 au, P < 0.01) relative to controls. Both mean (88 +/- 3 vs. 91 +/- 2 mmHg, P = 0.4) and diastolic (DBP) (72 +/- 3 vs. 73 +/- 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 +/- 0.5 vs. -5.4 +/- 0.5 bursts.100 heart beats( 1).mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 +/- 24 vs. -210 +/- 24 au.100 heart beats(-1).mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 +/- 8 vs. 36 +/- 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism. PMID- 26139216 TI - Left atrial phasic function interacts to support left ventricular filling during exercise in healthy athletes. AB - We studied the contribution of phasic left atrial (LA) function to left ventricular (LV) filling during exercise. We hypothesized that reduced LV filling time at moderate-intensity exercise limits LA passive emptying and increases LA active emptying. Twenty endurance-trained males (55 +/- 6 yr) were studied at rest and during light- (~100 beats/min) and moderate-intensity (~130 beats/min) exercise. Two-dimensional and Doppler echocardiography were used to assess phasic volumes and diastolic function. LV end-diastolic volume increased from rest to light exercise (54 +/- 6 to 58 +/- 5 ml/m(2), P < 0.01) and from light to moderate exercise (58 +/- 5 to 62 +/- 6 ml/m(2), P < 0.01). LA maximal volume increased from rest to light exercise (26 +/- 4 to 30 +/- 5 ml/m(2), P < 0.01) related to atrioventricular plane displacement (r = 0.55, P < 0.005), without further change at moderate exercise. LA passive emptying increased at light exercise (9 +/- 2 to 13 +/- 3 ml/m(2), P < 0.01) and then returned to baseline at moderate exercise, whereas LA active emptying increased appreciably only at moderate exercise (6 +/- 2 to 14 +/- 3 ml/m(2), P < 0.01). Thus, the total atrial emptying volume did not increase beyond light exercise, and the increase in LV filling at moderate exercise could be attributed primarily to an increase in the conduit flow volume (19 +/- 3 to 25 +/- 5 ml/m(2), P < 0.01). LA filling increases during exercise in relation to augmented LV longitudinal contraction. Conduit flow increases progressively with exercise in athletes, although this is driven by LV properties rather than intrinsic LA function. The pump function of the LA augments only at moderate exercise due to a reduced diastolic filling time and the Frank-Starling mechanism. PMID- 26139217 TI - Short-term high-intensity interval and moderate-intensity continuous training reduce leukocyte TLR4 in inactive adults at elevated risk of type 2 diabetes. AB - Exercise can have anti-inflammatory effects in obesity, but the optimal type and intensity of exercise are not clear. This study compared short-term high intensity interval training (HIIT) with moderate-intensity continuous training (MICT) in terms of improvement in cardiorespiratory fitness, markers of inflammation, and glucose control in previously inactive adults at elevated risk of developing type 2 diabetes. Thirty-nine inactive, overweight/obese adults (32 women) were randomly assigned to 10 sessions over 2 wk of progressive HIIT (n = 20, four to ten 1-min sessions at ~90% peak heart rate, 1-min rest periods) or MICT (n = 19, 20-50 min at ~65% peak heart rate). Before and 3 days after training, participants performed a peak O2 uptake test, and fasting blood samples were obtained. Both HIIT (1.8 +/- 0.4 vs. 1.9 +/- 0.4 l/min, pre vs. post) and MICT (1.8 +/- 0.5 vs. 1.9 +/- 0.5 l/min, pre vs. post) improved peak O2 uptake (P < 0.001) and lowered plasma fructosamine (P < 0.05). Toll-like receptor (TLR) 4 (TLR4) expression was reduced on lymphocytes and monocytes after both HIIT and MICT (P < 0.05) and on neutrophils after MICT (P < 0.01). TLR2 on lymphocytes was reduced after HIIT and MICT (P < 0.05). Plasma inflammatory cytokines were unchanged after training in both groups, but MICT led to a reduction in fasting plasma glucose (P < 0.05, 5.9 +/- 1.0 vs. 5.6 +/- 1.0 mmol/l, pre vs. post). Ten days of either HIIT or MICT can improve cardiorespiratory fitness and glucose control and lead to reductions in TLR2 and TLR4 expression. MICT, which involved a longer duration of exercise, may be superior for reducing fasting glucose. PMID- 26139218 TI - Association of microparticles and neutrophil activation with decompression sickness. AB - Decompression sickness (DCS) is a systemic disorder, assumed due to gas bubbles, but additional factors are likely to play a role. Circulating microparticles (MPs)--vesicular structures with diameters of 0.1-1.0 MUm--have been implicated, but data in human divers have been lacking. We hypothesized that the number of blood-borne, Annexin V-positive MPs and neutrophil activation, assessed as surface MPO staining, would differ between self-contained underwater breathing apparatus divers suffering from DCS vs. asymptomatic divers. Blood was analyzed from 280 divers who had been exposed to maximum depths from 7 to 105 meters; 185 were control/asymptomatic divers, and 90 were diagnosed with DCS. Elevations of MPs and neutrophil activation occurred in all divers but normalized within 24 h in those who were asymptomatic. MPs, bearing the following proteins: CD66b, CD41, CD31, CD142, CD235, and von Willebrand factor, were between 2.4- and 11.7-fold higher in blood from divers with DCS vs. asymptomatic divers, matched for time of sample acquisition, maximum diving depth, and breathing gas. Multiple logistic regression analysis documented significant associations (P < 0.001) between DCS and MPs and for neutrophil MPO staining. Effect estimates were not altered by gender, body mass index, use of nonsteroidal anti-inflammatory agents, or emergency oxygen treatment and were modestly influenced by divers' age, choice of breathing gas during diving, maximum diving depth, and whether repetitive diving had been performed. There were no significant associations between DCS and number of MPs without surface proteins listed above. We conclude that MP production and neutrophil activation exhibit strong associations with DCS. PMID- 26139219 TI - A strategy for oxygen conditioning at high altitude: comparison with air conditioning. AB - Large numbers of people live or work at high altitude, and many visit to trek or ski. The inevitable hypoxia impairs physical working capacity, and at higher altitudes there is also cognitive impairment. Twenty years ago oxygen enrichment of room air was introduced to reduce the hypoxia, and this is now used in dormitories, hotels, mines, and telescopes. However, recent advances in technology now allow large amounts of oxygen to be obtained from air or cryogenic oxygen sources. As a result it is now feasible to oxygenate large buildings and even institutions such as hospitals. An analogy can be drawn between air conditioning that has improved the living and working conditions of millions of people who live in hot climates and oxygen conditioning that can do the same at high altitude. Oxygen conditioning is similar to air conditioning except that instead of cooling the air, the oxygen concentration is raised, thus reducing the equivalent altitude. Oxygen conditioning on a large scale could transform living and working conditions at high altitude, where it could be valuable in homes, hospitals, schools, dormitories, company headquarters, banks, and legislative settings. PMID- 26139220 TI - Identification of mouse gaits using a novel force-sensing exercise wheel. AB - The gaits that animals use can provide information on neurological and musculoskeletal disorders, as well as the biomechanics of locomotion. Mice are a common research model in many fields; however, there is no consensus in the literature on how (and if) mouse gaits vary with speed. One of the challenges in studying mouse gaits is that mice tend to run intermittently on treadmills or overground; this paper attempts to overcome this issue with a novel exercise wheel that measures vertical ground reaction forces. Unlike previous instrumented wheels, this wheel is able to measure forces continuously and can therefore record data from consecutive strides. By concatenating the maximum limb force at each time point, a force trace can be constructed to quantify and identify gaits. The wheel was three dimensionally printed, allowing the design to be shared with other researchers. The kinematic parameters measured by the wheel were evaluated using high-speed video. Gaits were classified using a metric called "3S" (stride signal symmetry), which quantifies the half wave symmetry of the force trace peaks. Although mice are capable of using both symmetric and asymmetric gaits throughout their speed range, the continuum of gaits can be divided into regions based on the frequency of symmetric and asymmetric gaits; these divisions are further supported by the fact that mice run less frequently at speeds near the boundaries between regions. The boundary speeds correspond to gait transition speeds predicted by the hypothesis that mice move in a dynamically similar fashion to other legged animals. PMID- 26139221 TI - Positional differences in reactive hyperemia provide insight into initial phase of exercise hyperemia. AB - Studies have reported a greater blood flow response to muscle contractions when the limb is below the heart compared with above the heart, and these results have been interpreted as evidence for a skeletal muscle pump contribution to exercise hyperemia. If limb position affects the blood flow response to other vascular challenges such as reactive hyperemia, this interpretation may not be correct. We hypothesized that the magnitude of reactive hyperemia would be greater with the limb below the heart. Brachial artery blood flow (Doppler ultrasound) and blood pressure (finger-cuff plethysmography) were measured in 10 healthy volunteers. Subjects lay supine with one arm supported in two different positions: above or below the heart. Reactive hyperemia was produced by occlusion of arterial inflow for varying durations: 0.5 min, 1 min, 2 min, or 5 min in randomized order. Peak increases in blood flow were 77 +/- 11, 178 +/- 24, 291 +/- 25, and 398 +/- 33 ml/min above the heart and 96 +/- 19, 279 +/- 62, 550 +/- 60, and 711 +/- 69 ml/min below the heart (P < 0.05). Thus a standard stimulus (vascular occlusion) elicited different responses depending on limb position. To determine whether these differences were due to mechanisms intrinsic to the arterial wall, a second set of experiments was performed in which acute intraluminal pressure reduction for 0.5 min, 1 min, 2 min, or 5 min was performed in isolated rat soleus feed arteries (n = 12). The magnitude of dilation upon pressure restoration was greater when acute pressure reduction occurred from 85 mmHg (mimicking pressure in the arm below the heart; 28.3 +/- 7.9, 37.5 +/- 5.9, 55.1 +/- 9.9, and 68.9 +/ 8.6% dilation) than from 48 mmHg (mimicking pressure in the arm above the heart; 20.8 +/- 4.8, 22.6 +/- 4.4, 31.2 +/- 5.8, and 49.2 +/- 7.1% dilation). These data support the hypothesis that arm position differences in reactive hyperemia are at least partially mediated by mechanisms intrinsic to the arterial wall. Overall, these results suggest the need to reevaluate studies employing positional changes to examine muscle pump influences on exercise hyperemia. PMID- 26139222 TI - Combining quantitative 2D and 3D image analysis in the serial block face SEM: application to secretory organelles of pancreatic islet cells. AB - A combination of two-dimensional (2D) and three-dimensional (3D) analyses of tissue volume ultrastructure acquired by serial block face scanning electron microscopy can greatly shorten the time required to obtain quantitative information from big data sets that contain many billions of voxels. Thus, to analyse the number of organelles of a specific type, or the total volume enclosed by a population of organelles within a cell, it is possible to estimate the number density or volume fraction of that organelle using a stereological approach to analyse randomly selected 2D block face views through the cells, and to combine such estimates with precise measurement of 3D cell volumes by delineating the plasma membrane in successive block face images. The validity of such an approach can be easily tested since the entire 3D tissue volume is available in the serial block face scanning electron microscopy data set. We have applied this hybrid 3D/2D technique to determine the number of secretory granules in the endocrine alpha and beta cells of mouse pancreatic islets of Langerhans, and have been able to estimate the total insulin content of a beta cell. PMID- 26139224 TI - Interprofessional education: First steps. PMID- 26139223 TI - Association of Interleukin-10 gene promoter polymorphisms with obstructive sleep apnea. AB - BACKGROUND: Interleukin-10 (IL) is an anti-inflammatory cytokine that regulates normal sleep patterns, and recent studies have reported that it is a potential useful biomarker to identify presence and severity of sleep apnea syndrome (OSAS). Promoter polymorphisms of IL-10 gene have been associated with altered expression levels, which contributes to OSAS. OBJECTIVE: The aim of this study was to determine the prevalence of -1082 G/A, -819 C/T, and -592 C/A promoter polymorphisms of IL-10 gene in individuals with OSAS and controls. SUBJECTS AND METHODS: An open-label study was performed in the Otorhinolaryngology and Sleep Disorders Outpatient Clinics. One hundred four cases with OSAS were included as the study group, and 78 individuals without OSAS were included as the controls. DNAs were extracted from peripheral blood leukocytes, and the sites that encompassed those polymorphisms were identified by DNA sequencing analyses. Data were analyzed with SNPStats and multifactor dimensionality reduction (MDR) software. RESULTS: The prevalence of OSAS was higher in males in the study group when compared to controls (P = 0.0003). The IL-10-1082 G/A, -819 C/T, and -592 C/A SNPs, and their minor alleles were associated with a significantly increased risk for OSAS compared to the controls (P ? 0.05 for all). Furthermore, ATA haplotype frequency was significantly higher in the study group compared to the control group, but the GCC haplotype frequency was lower (P = 0.0001 and P = 0.0001). As indicated in MDR analysis, combinations of IL-10 gene were associated with OSAS in single-, double-, and triple-locus analyses. CONCLUSION: The prevalences of the IL-10 gene promoter polymorphisms were different in OSAS patients and the controls in Turkish population. IL-10 gene polymorphisms may lead to altered inflammatory cascade, which might contribute to OSAS. Further studies on larger cohorts are needed to validate our findings. PMID- 26139227 TI - Photocurrent generation in a light-harvesting system with multifunctional artificial nanochannels. AB - We develop an artificial light-harvesting system for photocurrent generation. Platinized TiO2 nanochannels are used as ultraviolet-light-harvesting antennae, which generate a transmembrane electrochemical gradient by asymmetric work function driven photochemical reactions. As a result, a potential difference is formed across the nanochannels, producing a photocurrent flowing through the external circuit. PMID- 26139228 TI - Increased risk of contrast-induced acute kidney injury in patients with pulmonary thromboembolism. AB - INTRODUCTION: Computed tomography pulmonary angiography (CTPA) is currently an effective, reliable and widely employed diagnostic test for pulmonary thromboembolism (PT). PT harbors intrinsic clinical and biochemical abnormalities which may be associated with an increased risk of contrast-induced acute kidney injury (CIAKI). OBJECTIVES: To assess the incidence and risk factors of CIAKI among patients with PT diagnosed with CTPA. METHODS: One hundred and twenty-two consecutive patients who had been diagnosed with PT using CTPA between February 2006 and December 2010 were evaluated retrospectively. In addition to the classical risk factors of CIAKI, arterial blood gases, CTPA and transthoracic echocardiography findings of the patients were also recorded. RESULTS: The incidence of CIAKI was 13.1%. There were statistically important differences with respect to age, the presence of congestive heart failure (CHF), the use of angiotensin converting enzyme inhibitor-angiotensin II receptor blocker drugs (ACEI-ARB), the arterial blood pH (ABpH) and the length of hospitalization between the two groups of patients who developed (n:16) and did not develop (n:106) CIAKI. In the logistic regression analysis, age and ABpH were preserved in the final equation. CONCLUSION: The incidence of CIAKI among PT patients is significantly higher than the expected average. Older age, the presence of CHF, the use of ACEI-ARB, and additionally, low ABpH are important risk factors of CIAKI in patients with PT. Hypoxemia and low bicarbonate levels intrinsic to PT may contribute to the increased risk of CIAKI in this patient population and their correction may carry a prophylactic potential. PMID- 26139229 TI - Meta-analysis of statin therapy in maintenance dialysis patients. AB - The effects of statin therapy in patients on maintenance dialysis remained uncertain. We conducted a meta-analysis to investigate the effects of statin on major clinical outcomes. We systematically searched Pubmed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang and Chinese Technological Journal of Database for randomized controlled trials (RCTs). Criteria for inclusion were RCTs on statins therapy versus placebo, >3 months of follow-up. The outcomes were serum level of low density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), high sensitivity C-reactive protein (hs-CRP) and albumin (ALB), all cardiac events, cardiovascular deaths and all-cause mortality. Twenty-one trials were identified, providing data for 8186 patients on maintenance dialysis. Statin therapy reduced LDL-C (weighted mean difference [WMD] = -0.74 mmol/L; 95%CI [-0.96, -0.52], p < 0.00001), TG (WMD = -0.36 mmol/L; 95%CI [-0.57, -0.14], p = 0.001), and hs-CRP (WMD = -3.98 mg/L; 95%CI [-5.24, -2.72], p < 0.00001), elevated HDL-C (WMD = 0.25 mmol/L; 95%CI [0.10, 0.39], p = 0.0007) and ALB (WMD = 1.70 g/L; 95%CI [0.19, 3.21], p = 0.03) significantly comparing with placebo. Statin therapy also had benefit in reducing all cardiac events (relative risk [RR] = 0.90; 95%CI [0.83, 0.97], p = 0.006), but had no effect on cardiovascular deaths (RR = 0.97; 95%CI [0.88, 1.07], p = 0.54) or all-cause mortality (RR = 0.98; 95%CI [0.93, 1.04], p = 0.49). In conclusion, statins had no impact on all-cause or cardiovascular mortality, while there was an overall significant improvement for dyslipidemia, hs-CRP, hypoalbuminemia and cardiovascular events in dialysis patients. PMID- 26139230 TI - The evolution of central nervous system prophylaxis for patients with acute lymphoblastic leukemia. PMID- 26139231 TI - LONG-TERM OUTCOME IN PEDIATRIC TRICHOTILLOMANIA. AB - OBJECTIVE: To examine long-term outcome in children with trichotillomania. METHOD: We conducted follow-up clinical assessments an average of 2.8 +/- 0.8 years after baseline evaluation in 30 of 39 children who previously participated in a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) for pediatric trichotillomania. Our primary outcome was change in hairpulling severity on the Massachusetts General Hospital Hairpulling Hospital Hairpulling Scale (MGH-HPS) between the end of the acute phase and follow-up evaluation. We also obtained secondary measures examining styles of hairpulling, comorbid anxiety and depressive symptoms, as well as continued treatment utilization. We examined both correlates and predictors of outcome (change in MGH-HPS score) using linear regression. RESULTS: None of the participants continued to take NAC at the time of follow-up assessment. No significant changes in hairpulling severity were reported over the follow-up period. Subjects reported significantly increased anxiety and depressive symptoms but improvement in automatic pulling symptoms. Increased hairpulling symptoms during the follow-up period were associated with increased depression and anxiety symptoms and increased focused pulling. Older age and greater focused pulling at baseline assessment were associated with poor long-term prognosis. CONCLUSIONS: Our findings suggest that few children with trichotillomania experience a significant improvement in trichotillomania symptoms if behavioral treatments are inaccessible or have failed to produce adequate symptom relief. Our findings also confirm results of previous cross-sectional studies that suggest an increased risk of depression and anxiety symptoms with age in pediatric trichotillomania. Increased focused pulling and older age among children with trichotillomania symptoms may be associated with poorer long-term prognosis. PMID- 26139232 TI - Bone Characteristics and Their Determinants in Adolescents and Young Adults with Early-Onset Severe Obesity. AB - Childhood obesity is associated with compromised bone health. We studied bone characteristics and their determinants in obese young adults. The study included 68 subjects with early-onset severe obesity and 73 normal-weight controls. Data on physical activity (PA), diet and smoking were collected. Bone characteristics were measured using peripheral QCT. The obese and control subjects were similar in age (mean 19.6 +/- 2.6 years) and height but BMIs differed (39.7 and 22.6 kg/m(2)). A clustering of unhealthy lifestyles was marked: Obese subjects reported less supervised PA in childhood, adolescence and currently (p < 0.03) and were more likely to smoke (p = 0.005), and had a lower healthy eating index (HEI) (p = 0.007) but similar alcohol consumption compared with controls. In obese women, all crude bone characteristics were higher than in controls; in men, the differences were smaller. Associations of lifestyle factors with bone characteristics were tested using partial correlations. Independently of BMI, supervised PA in adolescence and alcohol consumption were related positively to bone characteristics in both groups. HEI associated positively with bone characteristics only in controls, while smoking was a positive determinant of bone characteristics only in obese subjects. The multivariate model showed that the contribution of lifestyle factors to bone characteristics was minimal compared with BMI. Early-onset obesity is accompanied by poor dietary quality, sedentary lifestyle, and more frequent smoking, but the overall contribution of these lifestyle factors to bone strength is limited. Bone strength is more likely to be compromised in men and in unloaded bone sites in subjects with early-onset severe obesity. The impact of obesity-related endocrine changes on bone characteristics need to be evaluated in future studies. PMID- 26139233 TI - Response to 'Assessment of vitiligo severity: patient-reported estimates are not accurate'. PMID- 26139235 TI - L40m is wasted on GP data extraction IT system that does not work properly. PMID- 26139234 TI - Monogenic and chromosomal causes of isolated speech and language impairment. AB - The importance of a precise molecular diagnosis for children with intellectual disability, autism spectrum disorder and epilepsy has become widely accepted and genetic testing is an integral part of the diagnostic evaluation of these children. In contrast, children with an isolated speech or language disorder are not often genetically evaluated, despite recent evidence supporting a role for genetic factors in the aetiology of these disorders. Several chromosomal copy number variants and single gene disorders associated with abnormalities of speech and language have been identified. Individuals without a precise genetic diagnosis will not receive optimal management including interventions such as early testosterone replacement in Klinefelter syndrome, otorhinolaryngological and audiometric evaluation in 22q11.2 deletion syndrome, cardiovascular surveillance in 7q11.23 duplications and early dietary management to prevent obesity in proximal 16p11.2 deletions. This review summarises the clinical features, aetiology and management options of known chromosomal and single gene disorders that are associated with speech and language pathology in the setting of normal or only mildly impaired cognitive function. PMID- 26139236 TI - Long-term renal outcomes in a cohort of 1814 Chinese patients with biopsy-proven lupus nephritis. AB - In the present study, we observed the renal outcomes in a cohort of 1814 Chinese patients with biopsy-proven lupus nephritis (LN) and evaluated the risk factors associated with poor renal prognosis. The 5 -, 10 -, 15 - and 20-year renal survival rates were 93.1%, 87.9%, 81.0% and 68.3%, respectively. Gender, LN duration, mean arterial pressure (MAP), proteinuria, serum creatinine, haemoglobin and pathological classification at the time of biopsy were independent risk factors for end-stage renal disease (ESRD). The long-term renal outcomes of patients with class II LN were unfavorable as opposed to those with class V. Additionally, the time-average proteinuria (TA-Pro) and the time-average mean arterial pressure (TA-MAP) during the follow-up were important risk factors for ESRD, with better predictive values than the baseline proteinuria and MAP. The results underscore the need for proteinuria and blood pressure control during follow-up in patients with LN; proteinuria levels should be controlled at least to < 1.0 g/24 h, and optimally to < 0.5 g/24 h; MAP should not exceed 96.5 mmHg. More attention should be paid to class II LN and emphasis should be placed on recurrence prevention of class II LN. PMID- 26139237 TI - Plasma Membrane Ca2+-Permeable Channels are Differentially Regulated by Ethylene and Hydrogen Peroxide to Generate Persistent Plumes of Elevated Cytosolic Ca2+ During Transfer Cell Trans-Differentiation. AB - The enhanced transport capability of transfer cells (TCs) arises from their ingrowth wall architecture comprised of a uniform wall on which wall ingrowths are deposited. The wall ingrowth papillae provide scaffolds to amplify plasma membranes that are enriched in nutrient transporters. Using Vicia faba cotyledons, whose adaxial epidermal cells spontaneously and rapidly (hours) undergo a synchronous TC trans-differentiation upon transfer to culture, has led to the discovery of a cascade of inductive signals orchestrating deposition of ingrowth wall papillae. Auxin-induced ethylene biosynthesis initiates the cascade. This in turn drives a burst in extracellular H2O2 production that triggers uniform wall deposition. Thereafter, a persistent and elevated cytosolic Ca(2+) concentration, resulting from Ca(2+) influx through plasma membrane Ca(2+) permeable channels, generates a Ca(2+) signal that directs formation of wall ingrowth papillae to specific loci. We now report how these Ca(2+)-permeable channels are regulated using the proportionate responses in cytosolic Ca(2+) concentration as a proxy measure of their transport activity. Culturing cotyledons on various combinations of pharmacological agents allowed the regulatory influence of each upstream signal on Ca(2+) channel activity to be evaluated. The findings demonstrated that Ca(2+)-permeable channel activity was insensitive to auxin, but up-regulated by ethylene through two independent routes. In one route ethylene acts directly on Ca(2+)-permeable channel activity at the transcriptional and post-translational levels, through an ethylene receptor-dependent pathway. The other route is mediated by an ethylene-induced production of extracellular H2O2 which then acts translationally and post translationally to up-regulate Ca(2+)-permeable channel activity. A model describing the differential regulation of Ca(2+)-permeable channel activity is presented. PMID- 26139238 TI - [Safety and efficacy of growth hormone treatment: GeNeSIS study in Spain]. AB - INTRODUCTION: Country-specific information on pediatric GH therapy is available from multi-national studies. METHODS: A total of 1294 children in Spain enrolled in the observational Genetics and Neuroendocrinology of Short-stature International Study (GeNeSIS). Adverse events were assessed in all GH-treated patients (n=1267) and effectiveness in those with GH deficiency (GHD, 78%). RESULTS: Mean age at time of entry to the study was 9.8 years. GH was initiated at a median (Q1-Q3) 0.22 (0.20-0.25) mg/kg/week and administered for 2.8 (1.6 4.4) years. For 262 patients with GHD and 4-year data, mean (95% CI) height velocity was 4.3 (4.1 - 4.6) cm/year at baseline, 9.0 (8.7 to 9.4) cm/year at 1 year, and 5.5 (5.2 to 5.8) cm/year at 4-years. Height standard deviation score (SDS) was -2.48 (-2.58 to -2.38) at baseline and -1.18 (-1.28 to -1.08) at 4 years. Final height SDS minus target height SDS (n=241) was -0.09 (-0.20 to 0.02). In 1143 GH-treated patients with >=1 year follow-up, 93 (8.1%) reported treatment-emergent adverse events. Serious events were reported for 7 children, with 2 considered GH-related. CONCLUSION: These data confirm the benefit of GH replacement therapy on height gain for the patients in Spain. The safety profile was consistent with that already known for GH therapy. PMID- 26139239 TI - [D-lactic acidosis in a ten months old infant with short bowel syndrome: Early suspicion equals early treatment]. PMID- 26139240 TI - Decisions on statin therapy by patients' opinions about survival gains: cross sectional survey of general practitioners. AB - BACKGROUND: Guidelines for primary prevention of cardiovascular disease provide little guidance on how patients' preferences should be taken into account. We wanted to explore whether general practitioners (GPs) are sensitive to patient preferences regarding survival gains from statin therapy. METHODS: In a cross sectional, online survey 3,270 Norwegian GPs were presented with a 55 year old patient with an unfavourable cardiovascular risk profile. He expressed preferences for statin therapy by indicating a minimum survival gain that would be considered a substantial benefit. This survival gain varied across six versions of the vignette: 8, 4 and 2 years, and 12, 6 and 3 months, respectively. Participants were randomly allocated to one version only. We asked whether the GPs would recommend the patient to take a statin. Subsequently we asked the GPs to estimate the average survival gain of life long simvastatin therapy for patients with a similar risk profile. RESULTS: We received 1,296 responses (40 %). Across levels of survival gains (8 years to 3 months) the proportion of GPs recommending statin therapy did not vary significantly (OR per level 1.07, 95 % CI 0.99 to 1.16). The GP's own estimate of survival gain was a statistically significant predictor of recommending therapy (OR per year adjusted for the GPs' age, sex, speciality attainment and number of patients listed 3.07, CI 2.55 to 3.69). CONCLUSION: GPs were insensitive to patient preferences regarding survival gain when recommending statin therapy. The GPs' recommendations were strongly associated with their own estimates of survival gain. PMID- 26139241 TI - Ecology of aerobic anoxygenic phototrophs in aquatic environments. AB - Recognition of the environmental role of photoheterotrophic bacteria has been one of the main themes of aquatic microbiology over the last 15 years. Aside from cyanobacteria and proteorhodopsin-containing bacteria, aerobic anoxygenic phototrophic (AAP) bacteria are the third most numerous group of phototrophic prokaryotes in the ocean. This functional group represents a diverse assembly of species which taxonomically belong to various subgroups of Alpha-, Beta- and Gammaproteobacteria. AAP bacteria are facultative photoheterotrophs which use bacteriochlorophyll-containing reaction centers to harvest light energy. The light-derived energy increases their bacterial growth efficiency, which provides a competitive advantage over heterotrophic species. Thanks to their enzymatic machinery AAP bacteria are active, rapidly growing organisms which contribute significantly to the recycling of organic matter. This chapter summarizes the current knowledge of the ecology of AAP bacteria in aquatic environments, implying their specific role in the microbial loop. PMID- 26139242 TI - Individualized radiotherapy (iRT) concepts for locally advanced pancreatic cancer (LAPC): indications and prognostic factors. AB - BACKGROUND: Novel techniques in radiation oncology have significantly improved the therapeutic window in locally advanced pancreatic cancer LAPC. In about one third of the patients, chemoradiation can lead to secondary resectability, contributing to an increase in outcome. Dose-escalation approaches using stereotactic body radiotherapy (SBRT) or advanced treatments such as intensity modulated radiotherapy (IMRT) can exploit the biological benefits of hypofractionation, or use "dose painting" approaches to target defined subvolumes. Prognostic subgroups of patients have been identified, based on molecular markers such as CA 19-9, nutritional factors, diabetes or immunological properties of tumor and normal tissue. PURPOSE: The aim of the present manuscript is to summarize data on downsizing for locally advanced pancreatic cancer (LAPC) and to elucidate the role of individualized radiotherapy (iRT). CONCLUSION: Future concepts focus on iRT based on prognostic factors leading to a true personalized treatment. PMID- 26139243 TI - The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies. AB - The SWI/SNF multisubunit complex modulates chromatin structure through the activity of two mutually exclusive catalytic subunits, SMARCA2 and SMARCA4, which both contain a bromodomain and an ATPase domain. Using RNAi, cancer-specific vulnerabilities have been identified in SWI/SNF-mutant tumors, including SMARCA4 deficient lung cancer; however, the contribution of conserved, druggable protein domains to this anticancer phenotype is unknown. Here, we functionally deconstruct the SMARCA2/4 paralog dependence of cancer cells using bioinformatics, genetic, and pharmacologic tools. We evaluate a selective SMARCA2/4 bromodomain inhibitor (PFI-3) and characterize its activity in chromatin-binding and cell-functional assays focusing on cells with altered SWI/SNF complex (e.g., lung, synovial sarcoma, leukemia, and rhabdoid tumors). We demonstrate that PFI-3 is a potent, cell-permeable probe capable of displacing ectopically expressed, GFP-tagged SMARCA2-bromodomain from chromatin, yet contrary to target knockdown, the inhibitor fails to display an antiproliferative phenotype. Mechanistically, the lack of pharmacologic efficacy is reconciled by the failure of bromodomain inhibition to displace endogenous, full-length SMARCA2 from chromatin as determined by in situ cell extraction, chromatin immunoprecipitation, and target gene expression studies. Furthermore, using inducible RNAi and cDNA complementation (bromodomain- and ATPase-dead constructs), we unequivocally identify the ATPase domain, and not the bromodomain of SMARCA2, as the relevant therapeutic target with the catalytic activity suppressing defined transcriptional programs. Taken together, our complementary genetic and pharmacologic studies exemplify a general strategy for multidomain protein drug-target validation and in case of SMARCA2/4 highlight the potential for drugging the more challenging helicase/ATPase domain to deliver on the promise of synthetic-lethality therapy. PMID- 26139244 TI - AIP1 Expression in Tumor Niche Suppresses Tumor Progression and Metastasis. AB - Studies from tumor cells suggest that tumor-suppressor AIP1 inhibits epithelial mesenchymal transition (EMT). However, the role of AIP1 in the tumor microenvironment has not been examined. We show that a global or vascular endothelial cell (EC)-specific deletion of the AIP1 gene in mice augments tumor growth and metastasis in melanoma and breast cancer models. AIP1-deficient vascular environment not only enhances tumor neovascularization and increases premetastatic niche formation, but also secretes tumor EMT-promoting factors. These effects from AIP1 loss are associated with increased VEGFR2 signaling in the vascular EC and could be abrogated by systemic administration of VEGFR2 kinase inhibitors. Mechanistically, AIP1 blocks VEGFR2-dependent signaling by directly binding to the phosphotyrosine residues within the activation loop of VEGFR2. Our data reveal that AIP1, by inhibiting VEGFR2-dependent signaling in tumor niche, suppresses tumor EMT switch, tumor angiogenesis, and tumor premetastatic niche formation to limit tumor growth and metastasis. PMID- 26139246 TI - Community Acquired Severe Acute Kidney Injury Caused by Hantavirus-Induced Hemorrhagic Fever with Renal Syndrome Has a Favorable Outcome. AB - BACKGROUND: Puumala hantavirus (PUUV) induces an acute tubulointerstitial nephritis and acute kidney injury (AKI). Our aim was to evaluate the prognosis of severe AKI associated with PUUV infection. METHODS: We examined 556 patients who were treated at Tampere University Hospital during 1982-2013 for acute, serologically confirmed PUUV infection. Plasma creatinine was measured during hospitalization, convalescence, and 1, 2, and 5 years after the acute infection. RESULTS: Plasma creatinine concentration was elevated (>100 MUmol/l) in 459 (83%) patients, while altogether 189 patients (34%) had severe AKI defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3, that is, plasma creatinine >=353.6 MUmol/l (4.0 mg/dl) or need of dialysis. There were no fatal cases during the hospitalization or the following 3 months. Fatality rate during the years following PUUV infection did not differ between patients who had suffered from severe AKI versus those without severe AKI. Post-hospitalization plasma creatinine values were available for 188 (34%) patients. One month after the acute infection, patients with prior severe AKI had higher median plasma creatinine concentration (82 umol/l, range 54-184) than patients without severe AKI (74 umol/l, range 55-109, p = 0.005). After 1 year, no significant difference existed in median plasma creatinine concentrations between patients with (71 umol/l, range 36-123) and without prior severe AKI (72 umol/l, range 34-116, p = 0.711). After 5 years all but 1 patient had normal creatinine levels. CONCLUSIONS: In contrast to the worldwide well-accepted KDIGO criteria, severe AKI associated with PUUV infection is not associated with excess fatality but has a very good prognosis, both in the short and long terms. PMID- 26139245 TI - Development of a recombinant human ovarian (BG1) cell line containing estrogen receptor alpha and beta for improved detection of estrogenic/antiestrogenic chemicals. AB - Estrogenic endocrine-disrupting chemicals are found in environmental and biological samples, commercial and consumer products, food, and numerous other sources. Given their ubiquitous nature and potential for adverse effects, a critical need exists for rapidly detecting these chemicals. The authors developed an estrogen-responsive recombinant human ovarian (BG1Luc4E2) cell line recently accepted by the US Environmental Protection Agency (USEPA) and Organisation for Economic Co-operation and Development (OECD) as a bioanalytical method to detect estrogen receptor (ER) agonists/antagonists. Unfortunately, these cells appear to contain only 1 of the 2 known ER isoforms, ERalpha but not ERbeta, and the differential ligand selectivity of these ERs indicates that the currently accepted screening method only detects a subset of total estrogenic chemicals. To improve the estrogen screening bioassay, BG1Luc4E2 cells were stably transfected with an ERbeta expression plasmid and positive clones identified using ERbeta selective ligands (genistein and Br-ERbeta-041). A highly responsive clone (BG1LucERbetac9) was identified that exhibited greater sensitivity and responsiveness to ERbeta-selective ligands than BG1Luc4E2 cells, and quantitative reverse-transcription polymerase chain reaction confirmed the presence of ERbeta expression in these cells. Screening of pesticides and industrial chemicals identified chemicals that preferentially stimulated ERbeta-dependent reporter gene expression. Together, these results not only demonstrate the utility of this dual-ER recombinant cell line for detecting a broader range of estrogenic chemicals than the current BG1Luc4E2 cell line, but screening with both cell lines allows identification of ERalpha- and ERbeta-selective chemicals. PMID- 26139247 TI - A pathoanatomic approach to the management of mitral regurgitation. AB - Mitral regurgitation remains the most common global valvular heart disease. From otherwise unsuspecting healthy patients without overt symptoms to those with recalcitrant heart failure, mitral valve (MV) disease touches millions of patients per year. While MV prolapse without regurgitation remains benign, once regurgitation begins, quantification of severity is related to prognosis. Understanding the mechanism of regurgitation guides appropriate treatment. Current management guidelines emphasize early therapy after careful assessment of both anatomy and severity of mitral regurgitation. The objective of this review is to provide an update on the treatment of MV disease and to offer additional granularity on pathoanatomic decision making that may aid a more precise application of optimal guideline-directed therapy of primary and secondary mitral regurgitation. PMID- 26139248 TI - Western Blotting: Origin and Ascent of the Species. AB - Western blotting has survived as an essential tool of the research and clinical laboratory because it has maintained its everyday scientific usefulness while simultaneously evolving as a facile weapon to confront high-content analytical demands of proteomic and diagnostic screening. New approaches for imaging blotted proteins have emerged to complement the core methodology. PMID- 26139249 TI - Methods to Concentrate Proteins for Protein Isolation, Proteomic, and Peptidomic Evaluation. AB - In protein isolation, proteomic, or peptidomic procedures, protein solutions are often concentrated to remove solvents and undesirable molecules, to separate protein fractions or to increase protein concentrations. Proteins can be concentrated by precipitation from solution with ammonium sulfate, polyethylene glycol, organic solvent, trichloroacetic acid, potassium chloride/sodium dodecyl sulfate, and three-phase partitioning. Solvents can be removed by passage through a semipermeable barrier where protein solutions are forced against the barrier in a centrifuge tube or with increased pressure concentrating protein in the remaining solution. The semipermeable barrier can be surrounded by a hygroscopic reagent to draw the solvent across the membrane. Proteins can be concentrated by freeze-drying (lyophilization). All these methods to concentrate proteins are discussed. PMID- 26139250 TI - Measuring Protein Concentration on Nitrocellulose and After the Electrophoretic Transfer of Protein to Nitrocellulose. AB - Proteins bind to nitrocellulose membranes when applied directly or after electrophoretic transfer from polyacrylamide electrophoresis gels. Proteins can be stained for visualization with organic dyes Ponceau S, amido black, Coomassie Blue, and colloidal silver/gold and the intensity of the stain is directly proportional to the amount of protein present. Chemicals that interfere with dye/protein interactions in solution can be removed by washing the nitrocellulose after protein application. A method is described whereby protein-dye complexes attached to the nitrocellulose can be solubilized, dissolving the nitrocellulose and releasing dye into solution for detection by a spectrophotometer. The concentration of the dyes Ponceau S, amido black, and colloidal silver is proportional to the concentration of protein. Proteins transferred electrophoretically from SDS-PAGE, isoelectric focusing, or 2D gels to nitrocellulose can be stained with amido black, protein bands excised, and the bound dye detected in a spectrophotometer to quantify proteins in the individual protein bands. PMID- 26139251 TI - Detection of Blotted Proteins: Not All Blockers Are Created Equal. AB - Western blotting is a standard analytical technique for detection of proteins. It is dependent on a number of components; from the specificity of the primary antibody to the reduction of competing biomolecules present in the assay. Blocking agents are a critical component for western blotting protocols as these diminish nonspecific binding by blocking off-target sites on the membrane. A variety of blocking agents are available and these are selected in an empirical manner, as no single blocker is compatible with every system. The best blocking agent and method for any particular assay will be an optimized but not absolute choice. Here, we describe characteristics of the most common blocking agents used in western blotting and discuss their advantages and disadvantages. PMID- 26139252 TI - Protein Stains to Detect Antigen on Membranes. AB - Western blotting (protein blotting/electroblotting) is the gold standard in the analysis of complex protein mixtures. Electroblotting drives protein molecules from a polyacrylamide (or less commonly, of an agarose) gel to the surface of a binding membrane, thereby facilitating an increased availability of the sites with affinity for both general and specific protein reagents. The analysis of these complex protein mixtures is achieved by the detection of specific protein bands on a membrane, which in turn is made possible by the visualization of protein bands either by chemical staining or by reaction with an antibody of a conjugated ligand. Chemical methods employ staining with organic dyes, metal chelates, autoradiography, fluorescent dyes, complexing with silver, or prelabeling with fluorophores. All of these methods have differing sensitivities and quantitative determinations vary significantly. This review will describe the various protein staining methods applied to membranes after western blotting. "Detection" precedes and is a prerequisite to obtaining qualitative and quantitative data on the proteins in a sample, as much as to comparing the protein composition of different samples. "Detection" is often synonymous to staining, i.e., the reversible or irreversible binding by the proteins of a colored organic or inorganic chemical. PMID- 26139253 TI - Fluorescent Labeling of Proteins and Its Application to SDS-PAGE and Western Blotting. AB - This chapter describes very simple fluorescent methods developed in our laboratory allowing the rapid monitoring of total protein patterns on both sodium dodecyl sulfate (SDS) polyacrylamide gels and western blots. The noncovalent dye Nile red (9-diethylamino-5H-benzo[alpha]phenoxazine-5-one) is used for the sensitive staining of proteins in SDS gels. This method is compatible with the electroblotting of protein bands and with the staining of the resulting blot with the covalent dye MDPF (2-methoxy-2,4-diphenyl-3(2H)-furanone). These staining procedures are applied sequentially; there is no need to run a duplicate unstained gel for protein blotting. Furthermore, since only the adduct formed by the reaction of MDPF with proteins is fluorescent, there is no need to destain the membrane after protein labeling. In addition, MDPF staining is compatible with further immunodetection of specific bands with polyclonal antibodies. Finally, using the adequate conditions described below, MDPF staining does not preclude the N-terminal sequence analysis of proteins in selected bands. PMID- 26139254 TI - Rapid, Antibody-Free Detection of Recombinant Proteins on Blots Using Enzyme Fragment Complementation. AB - Alternative, antibody-free techniques to western analysis of protein blots can offer reduced assay times for routine analysis of expression of recombinant proteins. We have adapted the commercially available enzyme fragment complementation technology to provide a rapid protein detection method for protein blots based on significantly reducing the number of incubation and washing steps used in traditional approaches, and eliminating the requirement for antibodies. In this chapter, we highlight the use of this assay for measuring recombinant protein expressed in mammalian cells for a range of applications, including dot blot screening of large numbers of different cell samples, assessment of protein integrity through detection of degradation bands, and characterization of posttranslational protein modifications such as glycosylation. PMID- 26139255 TI - Use of Nonradioactive Detection Method for North- and South-Western Blot. AB - Many proteins bind to nucleic acids. For the first characterization of novel proteins, a fast and simple technique for testing their nucleic acid binding capabilities is desirable. Here we describe the use of a North-western and South western blot protocol for the evaluation of the DNA and RNA binding abilities of a novel putative methyl transferase HSPC133 (METTL5). PMID- 26139256 TI - Immunoblotting Using Radiolabeled Reagents for Detection. AB - Development of immunoblots is commonly performed using enzyme-labeled antibodies which convert soluble substrates into insoluble colored products. A simple, rapid, and sensitive alternative method which produces low background and allows a rapid quantitative evaluation is the use of radiolabeled antibodies or protein A conjugates. Here we describe the use of iodinated secondary antibodies for immunodetection of an autoantigen during HPLC purification. PMID- 26139257 TI - Immunoblotting of Antigens: Whole, Strip, and New-Line Nitrocellulose Membrane Immunoblotting Using the Chemiluminescence Technique. AB - Antigen detection is a well-known tool in the scientific world that is used by clinicians and researchers to detect specific antigens in diagnosing diseases or for other medical/environmental discoveries. Antigen detection is introduced in various forms over the past decades. These techniques are often evaluated by their sensitivity, accuracy, and ease of use. One technique that has provided many advantages over typical immunochemical staining is the use of chemiluminescence. This technique has been used in various scientific fields, anywhere from clinical diagnosis to environmental research. The emission of visible radiation by compounds once exposed to sunlight has been known for centuries and currently is the main principle for chemiluminescence. Here, we introduce three different chemiluminescence techniques that are widely used in immunodetection of antigens: (a) whole membrane chemiluminescence detection, (b) strip membrane chemiluminescence detection, and PMID- 26139258 TI - Detection of Protein Carbonyls by Means of Biotin Hydrazide-Streptavidin Affinity Methods. AB - Oxidative posttranslational protein modifications occur as a normal process of cell biology and to a greater extent during pathogenic conditions. The detection and quantitation of protein oxidation has posed a continuing challenge to bioanalytical chemists because of the following reasons: The products of oxidative protein damage are chemically diverse; protein oxidation generally occurs at low background levels; and the complexity of biological samples introduces high background noise when standard techniques such as immunolabeling are applied to "dirty" tissue extracts containing endogenous immunoglobulins or small molecular weight, chemically reactive compounds has been developed which circumvents these difficulties by incorporating a biotin label at sites of protein carbonylation. Biotin hydrazide-labeled proteins are detectable using standard streptavidin-coupled detection techniques such as peroxidase-catalyzed chemiluminescence of immunoblots. Advantages of the biotin hydrazide-labeling technique are its sensitivity and its lack of reliance upon antibodies that inevitably suffer from nonspecific background noise and contaminating endogenous immunoglobulins. PMID- 26139259 TI - Direct Immunodetection of Antigens Within the Precast Polyacrylamide Gel. AB - Western blotting is one of the few basic techniques widely used in the study of proteins in life science research. Despite its prevalence, the procedure has remained practically unchanged for more than 20 years. Although the method is viewed as being error-prone and as requiring excessive hands-on time, it is still widely accepted because it provides sensitive and direct information about the protein characteristics. The process is attractive to researchers because it reduces the investment in instrumentation and setup. Here we describe a procedure that eliminates the transfer step of western blotting and allows for antigen detection directly within the polyacrylamide gel, thus minimizing the investment necessary for setting up western blotting. PMID- 26139260 TI - Quantitative Analysis of Signal Transduction with In-Cell Western Immunofluorescence Assays. AB - Protein levels and signaling events can be efficiently quantified in many samples with the In-Cell Western (ICW) cell-based assay. This quantitative immunofluorescence method streamlines experimental procedures and data analysis, so hundreds of samples can be processed in parallel with quantitative data output. Cells are cultured in microplates and treated with various drugs or conditions. After fixation and permeabilization of cells in the microplate wells, immunostaining is used to detect target proteins. Secondary antibodies conjugated with IRDye near-infrared (NIR) fluorescent dyes are used for multiplex detection and normalization; cell stains and DNA stains can also be used for cell number normalization. Fluorescent signals reflect the protein expression levels or signaling status of the cell population in each well. ICW assays are a powerful alternative to western blotting. Time-consuming, error-prone steps such as cell lysis, gel electrophoresis, and membrane transfer are eliminated. In situ detection of protein targets in fixed cells provides a relevant cellular context, and enables very rapid and precise quenching of cellular treatments. Results are consistent with western blotting, but precision and reproducibility are enhanced. ICW functional assays are used to analyze protein phosphorylation, monitor the timing and kinetics of signal transduction events, monitor cellular response to agonists and antagonists, and determine IC50 and EC50 values. Modified On-Cell Western (OCW) assays are used for analysis of cell surface proteins, receptor internalization and recycling, and fluorescent ligand binding studies. Here, we describe the basic methodology for In-Cell Western quantitative immunofluorescence assays. PMID- 26139261 TI - Ultrasensitive Protein Detection on Dot Blots and Western Blots with Semiconducting Polymer Dots. AB - We demonstrate ultrasensitive fluorescence imaging of proteins on dot blots and western blots using a bright, compact, and orange-emitting semiconducting polymer dot (CNPPV). We achieved a detection limit at the single-picogram level in dot blots; with conventional western blot, we detected 50 pg of transferrin and trypsin inhibitor after SDS-PAGE and transfer onto a PVDF membrane. In this protocol, we describe the preparation of Pdots and its streptavidin bioconjugate and the procedures of dot blot and western blots. PMID- 26139262 TI - Co-detection of Target and Total Protein by CyDye Labeling and Fluorescent ECL Plex Immunoblotting in a Standard Proteomics Workflow. AB - The qualitative and quantitative capabilities of 2-D electrophoresis and its use in widespread proteome analysis have been revolutionized over the past decade with the introduction of differential gel electrophoresis commonly known as DIGE. This highly sensitive CyDye protein labeling technique now attempts to advance conventional western blotting by the combination of DIGE labeling with ECL Plex CyDye conjugated secondary antibodies. The ability of this method to simultaneously visualize the total protein expression profile as well as the specific immunodetection of an individual protein species will significantly aid protein validation following 2-D gel separation by confirming the exact location of proteins of interest. This simple, rapid, and reproducible technique is demonstrated by 1-D and 2-D electrophoresis through the detection of the small 27 kDa heat shock protein (hsp 27), a protein known to be expressed in the human heart, from a complex cardiac protein extract. PMID- 26139263 TI - Using Biotinylated Proteins to Demonstrate Immunodetection of Antigens via Western Blotting, Dot Blots, and Immunohistochemistry. AB - Using biotinylated targets for detection by enzyme-linked avidin allows immunodetection methods to become more economic in cost and time as it negates the need for a specific primary antibody. Methods are described to use exogenously added biotin to complex biological samples to demonstrate western blotting, dot blots, and immunohistochemistry. These methods can be used in biological science tertiary teaching laboratories to allow novices to gain skills in a risk-free environment to promote student motivation and engagement. PMID- 26139264 TI - Calcium Binding by Ro 60 Multiple Antigenic Peptides on PVDF Membrane. AB - Antibodies directed against ribonucleoprotein (RNP) particles are observed in systemic lupus erythematosus. Ro RNP particle is one such target. It is composed of a 60 kDa protein (Ro 60 or SS-A) that is non-covalently associated with at least one of the four short uridine-rich RNAs (the hY RNAs). Previously, we showed that multiple antigenic peptides (MAPs) made from the sequence of the Ro 60 autoantigen could be used, using double-immunodiffusion studies, enzyme-linked immunosorbant assay, affinity chromatography, and surface plasmon resonance, to show intramolecular and intermolecular protein-protein interaction within the Ro 60 RNP particle. We also observed that calcium is important in mediating this interaction. We hypothesized, therefore, that 60 kDa Ro is a calcium-binding protein. To investigate this, we electrophoresed 60 kDa Ro MAPs, transferred them to PVDF membrane, and assayed calcium binding using the Quin-2 system. Several Ro 60 MAPs were found to bind calcium using this assay, as well as bovine serum albumin, another calcium-binding protein. However, a MAP constructed from the Sm autoantigen did not bind to calcium. These data, along with our observation regarding the involvement of calcium in protein-protein interaction occurring between Ro 60 antigen and Ro 60 MAPs, makes us propose that Ro 60 antigen is a calcium-binding protein. PMID- 26139265 TI - Sequential Use of Immunoblots for Characterization of Autoantibody Specificities. AB - Sera of patients with systemic autoimmune diseases frequently contain autoantibodies to nuclear autoantigens. Immunoblotting of recombinant and native autoantigens is a commonly used technique for the identification and characterization of autoantibody specificities. Here we describe an easy procedure which facilitates the comparison of antibody specificities by reusing the same immunoblot for at least three times in order to detect an abundantly expressed autoantigen in total cellular extracts. PMID- 26139266 TI - Nanogold Immunodetection Detection Systems for the Identification of Autoantigens by Western Blotting. AB - Nanogold-conjugated immunodetection systems are now widely and commercially available for use in a number of research applications including electron microscopy, light microscopy, and western blotting. Nanogold clusters are small, uniform in size, and stable, unlike gold colloids historically used in protein detection. Covalent linkage of nanogold particles to secondary antibodies prevents dissociation of the gold particles during the staining process, making protein detection reliable, antigen specific, and highly sensitive. Nanogold labeling is extremely versatile and can be used in conjunction with other staining methodologies including Alexa Fluor immunofluorescence detection to perform coupled staining procedures. Silver enhancement increases the limits of sensitivity for nanogold staining, thus improving detection signals for antigens with reduced expression levels. Herein, we describe the use of nanogold-silver detection as an immunodetection system for standard western blotting of autoantigens. PMID- 26139267 TI - Application of Intermittent Microwave Irradiation to Western Blot Analysis. AB - We established a shortened protocol for Western blot analysis using intermittent microwave irradiation. With this method, the procedure is completed within 1 h after applying the primary antibody, and thus greatly saves time. This procedure appears to be applicable to any antibody based on our experience of several years. PMID- 26139268 TI - Visualization of Unstained Protein Bands on PVDF. AB - In 1988, two separate investigators reported a novel method of detecting unstained protein bands on PVDF membranes using white light transillumination. This simple method exploits the intrinsic hydrophobicity of PVDF membrane, which enables the visual observation of transferred protein bands due to differential wetting patterns between protein bands and the membrane itself. This method applies only to hydrophobic PVDF membranes, because hydrophilic membranes such as nitrocellulose wet out completely, rendering the protein bands invisible by transillumination. Transilluminational protein visualization can detect submicrogram quantities of proteins while circumventing the use of protein stains, which can potentially interfere with downstream analysis such as N terminal sequencing. In this chapter, we demonstrate efficient transilluminational protein visualization on a recently introduced low fluorescence PVDF membrane, normally used for downstream fluorescent immunodetection. PMID- 26139269 TI - Multiplexed Fluorescent Immunodetection Using Low Autofluorescence Immobilon(r) FL Membrane. AB - By enabling greater signal linearity and multiplexed detection, fluorescent western immunodetection overcomes many of the inherent technical limitations associated with the traditional chemiluminescent detection method. However, the sensitivity of fluorescence detection can be severely compromised by high background autofluorescence of various blotting membranes. Here, we describe a low autofluorescence PVDF membrane (Immobilon((r))-FL membrane) optimized for fluorescent immunodetection, and we report its use in the quantitative fluorescent western immunodetection of biomarkers associated with Alzheimer's disease (AD). First, membrane autofluorescence of four different commercially available blotting membranes was compared. Immobilon((r))-FL membrane exhibited the lowest autofluorescence with substantially increased detection sensitivity. We also show that the fluorescent immunodetection exhibited greatly increased linear dynamic range (two orders of magnitude, log scale) compared to the traditional chemiluminescent methods (less than one order of magnitude). Immobilon((r))-FL membrane was then used to quantify the expression levels of previously reported biomarkers associated with AD (synaptophysin, GSK3beta, and GAP43). Total protein extracts from age-matched brain samples of three AD patients and three normal controls were used. Biomarker expression levels were normalized to that of a housekeeping protein (GAPDH) using multiplexed detection, conserving difficult-to-obtain biological tissue samples and minimizing experimental variation. We found that the expression of GSK3beta and GAP43 biomarkers were significantly reduced in AD brain samples compared to age-matched normal samples. In summary, combining fluorescent immunodetection with a low autofluorescent blotting membrane yields accurate and reliable multiplexed quantitation of AD biomarkers. While this report focuses on the quantitation of AD biomarkers, the described technique is applicable to comparing protein expression in other biological contexts as well. PMID- 26139270 TI - Cold Microwave-Enabled Protein Detection and Quantification. AB - Protein screening/detection is an essential tool in many laboratories. Owing to the relatively large time investments that are required by standard protocols, the development of methods with higher throughput while maintaining an at least comparable signal-to-noise ratio is highly beneficial in many research areas. This chapter describes how cold microwave technology can be used to enhance the rate of molecular interactions and provides protocols for dot blots, Western blots, and ELISA procedures permitting a completion of all incubation steps (blocking and antibody steps) within 24-45 min. PMID- 26139271 TI - TLC-Blot (Far-Eastern Blot) and Its Application to Functional Lipidomics. AB - A simple method for transfer of lipids-including phospholipids, glycolipids, and neutral lipids-from a high performance thin layer chromatography (HPTLC) plate to a polyvinylidene difluoride (PVDF) membrane, TLC-Blot (Far-Eastern Blot), and its biochemical applications are presented. This chapter presents the conventional procedures for separating lipid from tissue samples, cultured cells, and serum and the subsequent development of TLC. Individual lipids separated on an HPTLC plate can be transferred to the PVDF membrane quantitatively and also isolated from the lipid-blotted membrane by a one-step purification procedure. Immunodetection with monoclonal antibodies and treatment with lipid-metabolizing enzymes on the lipid-blotted membrane are possible. The method for identification of individual lipids transferred on the PVDF membrane using matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (TLC Blot/MALDI-TOF MS) is shown as a functional lipidomics application. PMID- 26139272 TI - Analysis of Electroblotted Proteins by Mass Spectrometry. AB - Identification of proteins by mass spectrometry is crucial for better understanding of many biological, biochemical, and biomedical processes. Here we describe two methods for the identification of electroblotted proteins by on membrane digestion prior to analysis by mass spectrometry. These on-membrane methods take approximately half the time of in-gel digestion and provide better digestion efficiency, due to the better accessibility of the protease to the proteins adsorbed onto the nitrocellulose, and better protein sequence coverage, especially for membrane proteins where large and hydrophobic peptides are commonly present. PMID- 26139273 TI - On-Membrane Renaturation of Recombinant Ro60 Autoantigen by Calcium Ions. AB - Calcium plays an important role in many biochemical processes in different cell types. This divalent cation interacts with specific calcium-binding proteins that serve as calcium sensors and regulatory proteins to mediate its function. Previously, we found that calcium was involved in the protein-protein interaction observed between Ro60 multiple antigenic peptides and Ro60 autoantigen. Since calcium bound Ro60 multiple antigenic peptides, we hypothesized that it would renature human recombinant Ro60 on a protein blot. We found that anti-Ro60 antibodies bound significantly higher to the recombinant Ro60 antigen that was incubated with calcium compared to that incubated without calcium on a polyvinylidene fluoride (PVDF) blot. Since the immunological epitopes of Ro60 are mainly conformational, we believe that calcium induced a more native tertiary structure in recombinant Ro60 autoantigen following blotting to a PVDF membrane. PMID- 26139274 TI - Phosphoprotein Detection on Protein Electroblot Using a Phosphate-Specific Fluorophore. AB - The reversible phosphorylation of phosphoproteins is a vital regulatory process for many cellular pathways. A reliable and simple fluorescent detection technique for phosphoproteins has been developed using a small-molecule organic fluorophore, Pro-Q Diamond dye. This was originally developed for use in gel staining, but a new formulation has allowed for its use in protein blotting. The dye binds noncovalently and selectively to the phosphate moiety, so proteins lacking phosphate groups and other macromolecules, such as DNA or RNA, are not detected. It uses a standard electrophoresis and electroblotting technique, which can blot the sample onto nitrocellulose membranes or polyvinylidene fluoride (PVDF). The electroblotting is followed by staining with the dye and destaining. The blot can then be read by multiple types of imaging devices such as a laser based gel scanner. This process is compatible with matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) and Edman sequencing. It can also be followed by standard chemiluminescent, colorimetric, and fluorogenic detection techniques used in immunoblotting. PMID- 26139275 TI - Purification of Tryptic Digests on Polyvinylidene Difluoride Membrane. AB - Minor impurities in tryptic peptide digests can affect the signal obtained in matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Therefore, it becomes necessary to purify the digests, especially those that fail to yield good mass spectra. Here, we describe a simple protocol using polyvinylidene difluoride membrane for purifying tryptic peptides prior to mass spectrometric analysis. The tryptic digest is spotted on a polyvinylidene difluoride membrane, air-dried, and washed. The membrane is then extracted with trifluoroacetic acid/acetonitrile and the extract is then subjected to matrix assisted laser desorption ionization time-of-flight mass spectrometry. This method enabled us to identify a cross-reactive D1 autoantigen on the surface of neutrophils that bound antibodies targeting Ro 60 autoantigen in systemic lupus erythematosus. PMID- 26139276 TI - Detection of Blotted Proteins on Nitrocellulose/PVDF Membranes by Alta. AB - We describe here a simple method of staining nitrocellulose/PVDF blots by Alta. This red-colored stain which is used as a cosmetic contains Crocein scarlet and Rhodamine B as the principal components. It is very cheap, is available as a ready-to-use liquid, and is as sensitive as the most commonly used stain Ponceau Red S. We further demonstrate that Crocein scarlet (one of the principal components) alone can be used for staining the blots with equal efficiency as well. The stained protein profile can be detected on a white light plate and documented in the usual manner. Detailed analysis indicates that this stain does not interfere with subsequent immunoreactions. Moreover, Alta is almost 100 times cheaper to the routinely used stain Ponceau Red S, and thus is an ideal alternative to the Ponceau Red S for staining blots during western blot analysis. PMID- 26139277 TI - Nonstripping "Rainbow" and Multiple Antigen Detection (MAD) Western Blotting. AB - A variation of immunoblotting method (the "Rainbow Western"), permits sequential detection of multiple antigens (MAD) on a single protein blot without stripping off prior antibodies. Because no stripping is involved, immobilized proteins are not lost from the membrane, thus allowing for multiple reprobings of the same membrane with different primary antibodies (>=12), retaining strong signal intensities for all sequential antibody probings. The procedure utilizes horseradish peroxidase (HRPase)-based detection with both a chemiluminescent and colorimetric substrate. Initial incubation of the blot with secondary antibody followed by colorimetric development prior to probing the blot with primary antibodies markedly reduces background in ECL-based detection procedures and permits sequential use of antibodies derived from a single species. In the "Rainbow Western," four different HRPase-colorimetric substrates that produce black, brown, red, and green colors are employed sequentially for detection and simultaneous display of four different antigens on the same membrane. By allowing large amounts of data to be obtained from a single blot, the MAD-immunoblotting and Rainbow Western methods have the potential for researchers to compare the expression of several proteins within a single biological sample. Both techniques could be particularly valuable for analysis of cellular populations that are difficult to isolate in large numbers or of clinical specimens where the amounts of protein samples is minute or only available on a one-time basis. PMID- 26139278 TI - Supported Molecular Matrix Electrophoresis. AB - Mucins are difficult to separate using conventional gel electrophoresis methods such as SDS-PAGE and agarose gel electrophoresis, owing to their large size and heterogeneity. On the other hand, cellulose acetate membrane electrophoresis can separate these molecules, but is not compatible with glycan analysis. Here, we describe a novel membrane electrophoresis technique, termed "supported molecular matrix electrophoresis" (SMME), in which a porous polyvinylidene difluoride (PVDF) membrane filter is used to achieve separation. This description includes the separation, visualization, and glycan analysis of mucins with the SMME technique. PMID- 26139279 TI - Parafilm-M(r), An Available Cost-Effective Alternative for Immuno-blot Pouches. AB - Commercially available standard immuno-blot pouches do play an efficient role in antibody incubation in performing an immuno-blot, but are not readily available in the laboratory and have to be specifically ordered. We have developed an equally efficient technique to make an immune-blot more cost-effective with more conservation of antibodies by using a common and readily available laboratory product Parafilm-M((r)). Parafilm-M((r)) which serves as a sealant for various items of laboratory equipment can be used for antibody incubation. Manually made Parafilm-M((r)) pouch has a clear advantage over standard immuno-blot pouches in terms of availability, cost-effectiveness, and consumption of antibodies that ultimately reduces the cost of an immuno-blot. We have performed a series of experiments to check the efficacy of both the techniques. Samples with equal amount of protein were analyzed on separate SDS PAGE gels. The proteins were transferred electrophoretically to the nitrocellulose membrane using Trans Blot((r)) TurboTM Mini Nitrocellulose Transfer Pack. Antibody incubation was done using standard immuno-blot pouch, standard container and Parafilm-M((r)) sealed pouch. The expression of protein was determined and the results of immuno-blots were compared. We found that antibodies are binding the membrane in Parafilm M((r)) pouches as efficiently as in container method or in standard immuno-blot pouches. By restricting the membrane, the surface area of the manually made Parafilm-M((r)) pouch can be reduced, less diluent is required to cover the membrane as a result less antibodies are consumed. We also calculated that each immuno-blot pouch cost around $0.1906, whereas the cost for Parafilm-M((r)) pouch is 0.0695 which is almost one-third the price of an immuno-blot pouch. Thus, Parafilm-M((r)) method distinctly provides a cost-effective solution for antibody incubation. PMID- 26139280 TI - Succinylation-Alcian Blue Staining of Mucins on Polyvinylidene Difluoride Membranes. AB - Alcian blue staining has been widely used to visualize acidic mucins and mucopolysaccharides in supported molecular matrix electrophoresis (SMME) and on membrane transferred from electrophoresis gels. Mucins with low acidic glycan content, however, cannot be stained with Alcian blue, which is one of the major drawbacks of this staining method. On the other hand, periodic acid-Schiff staining can selectively visualize glycoproteins, including mucins, regardless of the acidic residue content; however, periodic acid-Schiff staining decomposes glycans. Here, we introduce succinylation-Alcian blue staining as an alternative staining method to visualize mucins, regardless of the acidic residue content, and without glycan decomposition. PMID- 26139281 TI - Comparison of Chemiluminescence vs. Infrared Techniques for Detection of Fetuin-A in Saliva. AB - The western blotting technique for transfer and detection of proteins, named following the discovery of southern and northern blotting for DNA- and RNA blotting, respectively, has traditionally relied on the use of X-ray films to capture chemiluminescence. Recent advancements use super-cooled charge coupled devices (CCD) cameras to capture both chemiluminescence and fluorescence images, which exhibit a greater dynamic range compared to traditional X-ray film. Chemiluminescence detected by a CCD camera records photons and displays an image based on the amount of light generated as a result of a dynamic chemical reaction. Fluorescent detection with a CCD camera, on the other hand, is measured in a static state. Despite this advantage, researchers continue to widely use chemiluminescent detection methods due to the generally poor performance of fluorophores in the visible spectrum. Infrared imaging systems offer a solution to the dynamic reactions of chemiluminescence and the poor performance of fluorophores detected in the visible spectrum, by imaging fluorophores in the infrared spectrum. Infrared imaging is static, has a wide linear range, high sensitivity, and reduced autofluorescence and light scatter. A distinct advantage of infrared imaging is the ability to detect two target proteins simultaneously on the same blot which increases accuracy of quantification and comparison, while minimizing the need for stripping and reprobing. Here, we compare the methodology for chemiluminescent (UVP BioChemi) and infrared (UVP Odyssey) detection of salivary total and phosphorylated fetuin-A, a multifunctional protein associated with cardio-metabolic risk, and discuss the advantages and disadvantages of these methodologies. PMID- 26139282 TI - A Novel Methodology for Stripping and Reprobing of Western Blots Originally Developed with Colorimetric Substrate TMB. AB - Protein blotting is a widely used analytical technique for detection of specific protein(s) in a given sample of tissue or cell homogenate or extract. Both chemiluminescence (CL) and colorimetric detections can be used for imaging protein blots in western blotting. Here we describe a methodology for stripping such western blots, already developed with the colorimetric substrate TMB on nitrocellulose membrane and reprobing the blot (after stripping) for the detection of a second protein through CL. The stripping procedure utilizes a stripping buffer consisting of beta-mercaptoethanol, SDS, and Tris-HCl, while washing buffer consists of PBS added with 0.1 % Tween 20 and involves a series of steps facilitating accurate detection of the second protein in the stripped blot through CL. PMID- 26139283 TI - Other Notable Methods of Membrane Protein Detection: A Brief Review. AB - Several techniques have been employed to detect proteins on membranes. These include the use of quantum dot luminescent labels, oxyblot immunochemical detection, polymer immunocomplexes, "coupled" probing approach, in situ renaturation of proteins for detecting enzyme activities in crude or purified preparations, immunochromatographic assay, western-phosphatase assay, and use of Congo red dye (a cosmetic color named Alta), Pro-Q Emerald 488 dye, or amine reactive dye in combination with alkaline phosphatase- and horseradish peroxidase antibody conjugates for the simultaneous trichromatic fluorescence detection of proteins. Several methods have been used to improve the detection of proteins on membranes, including glutaraldehyde treatment of nitrocellulose blots, elimination of keratin artifacts in immunoblots probed with polyclonal antibodies, and washing of immunoblots with excessive water and manipulation of Tween-20 in wash buffer. These methods are briefly reviewed in this chapter. PMID- 26139284 TI - Nitrocellulose Membrane: The New Canvas. AB - The use of nitrocellulose membranes for invisible ink-messaging or marking for orientation purposes has been carried out with diluted alkaline phosphatase, followed by development with nitro blue tetrazolium/5-bromo-4-chloro-3-indolyl phosphate and chemiluminescence detection systems. Here, we show that nitrocellulose membrane can serve as a canvas for art using alkaline phosphatase and NBT/BCIP detection method. PMID- 26139285 TI - Invisible Ink Marking in ECL Membrane Assays. AB - Invisible ink and writing secret messages have been part of man's fantasy, having proven useful in clandestine and high sensitivity areas. Security inks, made up of invisible materials that give printed, anti-photocopy images capable of being read only under special environments, have become important. An ink formulation based on silicon(IV) 2,3-naphthalocyanine bis(trihexylsilyloxide) as colorant, invisible to the naked eye but infrared readable, has been described earlier. Biometric DNA ink has also been developed for security authentication. In lighter vein, many budding scientists and others have often experimented with writing secret messages on paper, either for purposes of fun or actually sending secret messages to friends. It involved the use of lemon juice, milk, or other solutions that could be used with a dip pen, brush, or a fountain pen to write invisible messages on a blank white paper. Words turn up as magic when the paper is exposed to heat in one form or the other. Here, we attempt to end this book on a slightly humorous note by showing that invisible messages can be written on nitrocellulose membranes (but not on polyvinylidene difluoride membranes) using an appropriately diluted horse radish peroxidase/alkaline phosphatase anti-IgG conjugate (rabbit, mouse, or human anti-IgG). The message is written on the membrane, preferably with a fountain pen, and the membrane is allowed to dry. Regular detection with enhanced chemiluminescence plus or nitro blue tetrazolium/5-bromo-4-chloro-3 indolyl phosphate systems is used to unravel the secret message. In addition, this method could be used to mark nitrocellulose membranes for orientation purposes using ECL detection system and thus can eliminate the use of autoradiography pens. PMID- 26139287 TI - Kelvin probe imaging of photo-injected electrons in metal oxide nanosheets from metal sulfide quantum dots under remote photochromic coloration. AB - Metal oxide and quantum dot (QD) heterostructures have attracted considerable recent attention as materials for developing efficient solar cells, photocatalysts, and display devices, thus nanoscale imaging of trapped electrons in these heterostructures provides important insight for developing efficient devices. In the present study, Kelvin probe force microscopy (KPFM) of CdS quantum dot (QD)-grafted Cs4W11O36(2-) nanosheets was performed before and after visible-light irradiation. After visible-light excitation of the CdS QDs, the Cs4W11O36(2-) nanosheet surface exhibited a decreased work function in the vicinity of the junction with CdS QDs, even though the Cs4W11O36(2-) nanosheet did not absorb visible light. X-ray photoelectron spectroscopy revealed that W(5+) species were formed in the nanosheet after visible-light irradiation. These results demonstrated that excited electrons in the CdS QDs were injected and trapped in the Cs4W11O36(2-) nanosheet to form color centers. Further, the CdS QDs and Cs4W11O36(2-) nanosheet composite films exhibited efficient remote photochromic coloration, which was attributed to the quantum nanostructure of the film. Notably, the responsive wavelength of the material is tunable by adjusting the size of QDs, and the decoloration rate is highly efficient, as the required length for trapped electrons to diffuse into the nanosheet surface is very short owing to its nanoscale thickness. The unique properties of this photochromic device make it suitable for display or memory applications. In addition, the methodology described in the present study for nanoscale imaging is expected to aid in the understanding of electron transport and trapping processes in metal oxide and metal chalcogenide heterostructure, which are crucial phenomena in QD based solar cells and/or photocatalytic water-splitting systems. PMID- 26139286 TI - ESKAPEing the labyrinth of antibacterial discovery. AB - Antimicrobial drug resistance is a growing threat to global public health. Multidrug resistance among the 'ESKAPE' organisms - encompassing Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - is of particular concern because they are responsible for many serious infections in hospitals. Although some promising agents are in the pipeline, there is an urgent need for new antibiotic scaffolds. However, antibacterial researchers have struggled to identify new small molecules with meaningful cellular activity, especially those effective against multidrug-resistant Gram-negative pathogens. This difficulty ultimately stems from an incomplete understanding of efflux systems and compound permeation through bacterial membranes. This Opinion article describes findings from target based and phenotypic screening efforts carried out at AstraZeneca over the past decade, discusses some of the subsequent chemistry challenges and concludes with a description of new approaches comprising a combination of computational modelling and advanced biological tools which may pave the way towards the discovery of new antibacterial agents. PMID- 26139288 TI - Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates. AB - The development of an efficacious Plasmodium falciparum malaria vaccine remains a top priority for global health. Vaccination with irradiated sporozoites is able to provide complete sterile protection through the action of CD8(+) T cells at the liver-stage of infection. However, this method is currently unsuitable for large-scale deployment and focus has instead turned to the development of sub unit vaccines. Sub-unit vaccine efforts have traditionally focused on two well known pre-erythrocytic antigens, CSP and TRAP, yet thousands of genes are expressed in the liver-stage. We sought to assess the ability of eight alternative P. falciparum pre-erythrocytic antigens to induce a high proportion of CD8(+) T cells. We show that all antigens, when expressed individually in the non-replicating viral vectors ChAd63 and MVA, are capable of inducing an immune response in mice. Furthermore, we also developed chimeric P. berghei parasites expressing the cognate P. falciparum antigen to enable assessment of efficacy in mice. Our preliminary results indicate that vectors encoding either PfLSA1 or PfLSAP2 are capable of inducing sterile protection dependent on the presence of CD8(+) T cells. This work has identified two promising P. falciparum liver-stage candidate antigens that will now undergo further testing in humans. PMID- 26139289 TI - Demographic and clinical factors associated with benzodiazepine prescription at discharge from psychiatric inpatient treatment. AB - OBJECTIVE: We sought to characterize diagnostic and treatment factors associated with receiving a prescription for benzodiazepines at discharge from a psychiatric inpatient unit. We hypothesized that engaging in individual behavioral interventions while on the unit would decrease the likelihood of receiving a benzodiazepine prescription at discharge. METHOD: This is an observational study utilizing medical chart review (n=1007) over 37 months (2008-2011). Descriptive statistics characterized patient demographics and diagnostic/prescription frequency. Multivariate regression was used to assess factors associated with receiving a benzodiazepine prescription at discharge. RESULTS: The sample was 61% female with mean age=40.5 (S.D.=13.6). Most frequent diagnoses were depression (54.7%) and bipolar disorder (18.6%). Thirty-eight percent of participants engaged in an individual behavioral intervention. Benzodiazepines were prescribed in 36% of discharges. Contrary to our hypothesis, individual behavioral interventions did not influence discharge benzodiazepine prescriptions. However, several other factors did, including having a substance use disorder [odds ratio (OR)=0.40]. Male sex (OR=0.56), Black race (OR=0.40) and age (OR=1.03) were nonclinical factors with strong prescribing influence. CONCLUSION: Benzodiazepines are frequently prescribed at discharge. Our results indicate strong racial and sex biases when prescribing benzodiazepines, even after controlling for diagnosis. PMID- 26139290 TI - Training reinforcement rates, resistance to extinction, and the role of context in reinstatement. AB - Behavior reduced as a consequence of extinction or intervention can relapse. According to behavioral momentum theory, the extent to which behavior persists and relapses once it has been eliminated depends on the relative training reinforcement rate among discriminative stimuli. In addition, studies of context renewal reveal that relapse depends on the similarity between the training stimulus context and the test stimulus context following disruption by extinction. In the present experiments with pigeons, we arranged different reinforcement rates in the presence of distinct discriminative stimuli across components of a multiple schedule. Following extinction, we attempted to reinstate responding in the presence of those target components with response independent food presentations. Importantly, we arranged the reinstating food presentations either within the target components or in separate components, either paired with extinction (Experiment 1) or reinforcement (Experiment 2) during baseline. Reinstatement increased with greater training reinforcement rates when the reinstating food presentations were arranged in the target components and the separate components paired with reinforcement during training. Reinstatement was smaller and was not systematically related to training reinforcement rates in the target components when reinstating food presentation occurred in separate components paired with extinction. These findings suggest that relapse depends on the history of reinforcement associated with the discriminative stimuli in which the relapse-inducing event occurs. PMID- 26139291 TI - Reply. PMID- 26139292 TI - PNPLA3 genetic variants determine hepatic steatosis in non-obese chronic hepatitis C patients. AB - The influence of patatin-like phospholipase domain-containing 3 (PNPLA3) genetic variants in the development of liver steatosis in Asian chronic hepatitis C patients remains elusive. A total of 1018 biopsy-proven chronic hepatitis C patients were enrolled for evaluation. The proportions of PNPLA3 rs738409 GG genotype carriage were 7.8% (44/563), 15.8% (58/367) and 19.3% (17/88) in patients with no (liver fat content < 5%), mild (5-33%) and moderate/severe (> 66%) hepatic steatosis, respectively (trend P < 0.001). Stepwise logistic regression analysis revealed that the strongest factor independently associated with steatosis was the carriage of the PNPLA3 rs738409 GG genotype (odds ratio [OR]/95% confidence intervals [CI]:2.34/1.557-3.515, P < 0.001). Among the patients with BMI < 24 kg/m(2), carriage of the rs738409 GG genotype was the only factor associated with hepatic steatosis (OR/CI:3.44/1.824-6.500, P < 0.001). PNPLA3 genetic variants had minimal effects on hepatic steatosis among overweight or obese patients. Compared to patients with BMI < 24 kg/m(2)/non-GG genotype, those with BMI >24 kg/m(2)/GG genotype were more likely to have hepatic steatosis (OR/CI:3.87/2.292-6.524, P < 0.001). In conclusions, both PNPLA3 genetic variants and BMI played important roles in hepatic steatosis among Asian chronic hepatitis C patients. However, the genetic effect was mainly restricted to non-obese patients. PMID- 26139293 TI - The alar rim flap: a novel technique to manage malpositioned lateral crura. AB - BACKGROUND: Alar cartilage malposition is a common anatomic variation in which the axis of the lateral crus lies cephalically and may be parallel to the cephalic septum. Malposition of the lateral crura may produce inward collapse of the alae that is observable on deep inspiration. OBJECTIVES: The authors performed the alar rim flap technique to treat patients with alar malposition and assessed functional and aesthetic outcomes. METHODS: Twelve patients who underwent primary open rhinoplasty with the alar rim flap technique were evaluated in a prospective study. A 2- or 3-mm caudal portion of the lateral crus was elevated from the underlying mucosa, pulled caudally, and extended with a cartilage graft. This extension of the alar rim flap was placed through the pyriform aperture for additional support. Patients completed pre- and postoperative questionnaires addressing nasal obstruction and underwent paranasal computed tomography. Patients received follow-up for an average of 16 months (range, 8-27 months). RESULTS: Patients with alar cartilage malposition and external valve insufficiency experienced aesthetic and functional improvements after rhinoplasty with the alar rim flap technique. No patients developed alar rim collapse or flap displacement. CONCLUSIONS: The alar rim flap technique is effective for the correction of malpositioned lateral crura and external valve insufficiency. Because this technique does not damage the scroll area, disruption of the internal valve area is avoided. LEVEL OF EVIDENCE: 4 Therapeutic. PMID- 26139294 TI - Nutrition labelling, marketing techniques, nutrition claims and health claims on chip and biscuit packages from sixteen countries - CORRIGENDUM. PMID- 26139295 TI - Mitral regurgitation following pericardiectomy for constrictive pericarditis. AB - Pericardiectomy is the only definitive treatment option for patients with constrictive pericarditis. We present the case of a 67-year-old man who developed new moderate to severe mitral regurgitation following phrenic nerve-to-phrenic nerve pericardiectomy for constrictive pericarditis. The severity of the regurgitation was followed up by serial echocardiography which showed improvement 19 days later and complete resolution at 9 months after surgery. Potential mechanisms explaining the evolution of this mitral valve dysfunction in the setting of pericardiectomy are postulated. PMID- 26139296 TI - Hemostasis Plug for an Electromagnetic Thermotherapy and Its Application for Liver Laceration. AB - Accident-induced liver trauma is a significant human health concern, as this organ is readily injured during periods at which the abdominal region is compromised. In this work, electromagnetic thermotherapy was successfully developed and employed in vitro and in vivo to treat livers that had been lacerated. Briefly, a new hemostasis plug was integrated with an electromagnetic thermotherapy system (ETS) to perform surgery on lacerated livers. The high frequency, alternating electromagnetic field (EMF) was generated by the ETS and was shown to induce a pre-set temperature increase within the hemostasis plug embedded in the target tissue. In order to prevent overheating and maintain a constant hemostasis temperature, a temperature feedback control system was utilized. The effect of the intensity of the EMF on the heating capacity of the ETS-hemostasis system was first explored. Furthermore, the relationship between the coagulation zone and operating temperature were investigated in vitro. By utilizing the temperature feedback control system, the hemostasis plug could be heated to a specific temperature for efficient hemostasis. With this approach, the optimal treatment temperature and time were investigated for liver laceration. Lacerated livers from New Zealand white rabbits were successfully treated with the hemostasis plug and ETS within a short period of time. When compared with the traditional perihepatic packing approach, the volume of blood loss from liver laceration surgeries treated by ETS has been dramatically reduced by 83%, suggesting a high therapeutic potential for this system. PMID- 26139297 TI - Coronary Stent Materials and Coatings: A Technology and Performance Update. AB - This paper reviews the current state of the art for coronary stent materials and surface coatings, with an emphasis on new technologies that followed on from first-generation bare metal and drug-eluting stents. These developments have been driven mainly by the need to improve long term outcomes, including late stent thrombosis. Biodegradable drug-eluting coatings aim to address the long term effects of residual durable polymer after drug elution; the SYNERGY, BioMatrix, and Nobori stents are all promising devices in this category, with minimal polymer through the use of abluminal coatings. Textured stent surfaces have been used to attached drug directly, without polymer; the Yukon Choice and BioFreedom stents have some promising data in this category, while a hydroxyapatite textured surface has had less success. The use of drug-filled reservoirs looked promising initially but the NEVO device has experienced both technical and commercial set backs. However this approach may eventually make it to market if trials with the Drug-Filled Stent prove to be successful. Non-pharmacological coatings such as silicon carbide, carbon, and titanium-nitride-oxide are also proving to have potential to provide better performance than BMS, without some of the longer term issues associated with DES. In terms of biological coatings, the Genous stent which promotes attachment of endothelial progenitor cells has made good progress while gene-eluting stents still have some practical challenges to overcome. Perhaps the most advancement has been in the field of biodegradable stents. The BVS PLLA device is now seeing increasing clinical use in many complex indications while magnesium stents continue to make steady advancements. PMID- 26139298 TI - Immuno-based detection of extracellular vesicles in urine as diagnostic marker for prostate cancer. AB - Extracellular vesicles (including the subclass exosomes) secreted by cells contain specific proteins and RNA that could be of interest in determining new markers. Isolation/characterization of PCa-derived exosomes from bodily fluids enables us to discover new markers for this disease. Unfortunately, isolation with current techniques (ultracentrifugation) is labor intensive and other techniques are still under development. The goal of our study was to develop a highly sensitive time-resolved fluorescence immunoassay (TR-FIA) for capture/detection of PCa-derived exosomes. In our assay, biotinylated capture antibodies against human CD9 or CD63 were incubated on streptavidin-coated wells. After application of exosomes, Europium-labeled detection antibodies (CD9 or CD63) were added. Cell medium from 37 cell lines was taken to validate this TR FIA. Urine was collected (after digital rectal exam) from patients with PCa (n = 67), men without PCa (n = 76). As a control, urine was collected from men after radical prostatectomy (n = 13), women (n = 16) and patients with prostate cancer without digital rectal exam (n = 16). Signal intensities were corrected for urinary PSA and creatinine. This TR-FIA can measure purified exosomes with high sensitivity and minimal background signals. Exosomes can be measured in medium from 37 cell lines and in urine. DRE resulted in a pronounced increase in CD63 signals. After DRE and correction for urinary PSA, CD9 and CD63 were significantly higher in men with PCa. This TR-FIA enabled us to measure exosomes with high sensitivity directly from urine and cell medium. This TR-FIA forms the basis for testing different antibodies directed against exosome membrane markers to generate disease-specific detection assays. PMID- 26139301 TI - The Shape of Training report: misreported evidence, unpersuasive excuses. PMID- 26139302 TI - [Outbreak of multidrug-resistant CTX-M-9-producing Enterobacter cloacae complex in an intensive care unit]. AB - INTRODUCTION: Clinical and epidemiological description of an outbreak in an intensive care unit (ICU) caused by a strain of multidrug-resistant Enterobacter cloacae complex carrying a CTX-M-9-type extended-spectrum beta-lactamase (ESBL). METHODS: A retrospective study of the clinical and epidemiological features of the outbreak caused by E.cloacae complex was performed. Identifying and studying the sensitivity of the strains were performed using the semi-automated system BD PhoenixTM, and the characterisation of ESBL using PCR and sequencing. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE). RESULTS: During February 2014, 6 patients (50% women; mean age: 61.5 years; age range: 44-76 years) admitted to the ICU of the Hospital of Pontevedra (CHOP) presented resistant E.cloacae complex isolates to extended-spectrum cephalosporins. Three patients developed infection; one had primary bacteraemia and septic shock, and 2 with ventilator-associated pneumonia. In the remaining three cases E.cloacae complex isolates were considered as colonisation. Phenotypic and genotypic analysis revealed that all isolates had the same PFGE profile and carried the same CTX-M-9 ESBL. The outbreak was controlled by improving universal precautions and contact isolation of patients infected and/or colonized. CONCLUSION: The clinical and epidemiological features of an outbreak in an ICU caused by E.cloacae complex carrying CTX-M-9 are described. PMID- 26139303 TI - Evaluation of a new rapid diagnostic test for the detection of influenza and RSV. AB - INTRODUCTION: Influenza viruses and respiratory syncytial virus (RSV) can cause an acute respiratory disease that occurs seasonally in epidemic waves. This retrospective study was conducted to evaluate the Sofia((r)) Influenza A+B and the Sofia((r)) RSV fluorescence immunoassays (FIAs), two novel rapid detection tests (RDTs) for influenza A and B and RSV. METHODS: Two hundred and nine breath samples were selected from patients with respiratory symptoms determined to be positive/negative for influenza A, influenza B or RSV using one of the reference diagnostic techniques, cell culture and/or RT-PCR (SimplexaTMFlu A/B & RSV). The Sofia Influenza A+B FIA was tested on 123 samples (63 from children and 60 from adults) and the Sofia RSV FIA was tested on 86 pediatric samples. Sensitivity and specificity values of both assays were calculated assuming the reference techniques as the gold standard. RESULTS: Sensitivity and specificity values for the Sofia Influenza A+B FIA were 73.1% and 97.8%, respectively. Sensitivity and specificity values for the Sofia RSV FIA were 87.5% and 86.7%, respectively. CONCLUSION: The sensitivity results obtained for the two assays were considerably higher than those reported for other RDTs. In conclusion, the Sofia Influenza A+B and the Sofia RSV FIAs are appropriate tools for the rapid diagnosis of these viruses. PMID- 26139300 TI - Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale. AB - OBJECTIVES: The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties. MATERIALS AND METHODS: The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged>=65years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naive. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria. RESULTS: Mean time taken to complete the GAH scale was 11.9+/-4.7min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's alpha: 0.610), and test-retest was excellent (ICC coefficients, 0.695 0.928). CONCLUSION: Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies. PMID- 26139304 TI - Achromobacter xylosoxidans infection in an adult cystic fibrosis unit in Madrid. AB - BACKGROUND: Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of colonization by this microorganism is variable, prevalence is increasing in CF units. METHODS: A microbiological/clinical study was conducted on of adult CF patients harboring A. xylosoxidans. Identification and susceptibility testing were performed using MicroScan (Siemens). Decline in lung function was assessed using the variable, annual percentage loss of FEV1 (forced expiratory volume in 1s). RESULTS: A. xylosoxidans was isolated in 18 (19.8%) of 91 patients over a 14-year period. Mean age was 26.6 years (18-39 years). Nine patients (9.8%) were chronically colonized. Piperacillin/tazobactam and imipenem were the most active antibiotics. Mean annual decline in lung function in chronically colonized patients was 2.49%. CONCLUSIONS: A. xylosoxidans is a major pathogen in CF. A decreased lung function was observed among patients who were chronically colonized by A. xylosoxidans. Antibiotic therapy should be started early in order to prevent chronic colonization by this microorganism. PMID- 26139305 TI - The impact of immunosuppressive therapy on QuantiFERON and tuberculin skin test for screening of latent tuberculosis in patients with inflammatory bowel disease scheduled for anti-TNF therapy. AB - OBJECTIVE: Patients with inflammatory bowel disease (IBD) should be routinely screened for latent tuberculosis (LTB) before starting anti-TNF therapy in order to prevent reactivation of LTB. Besides tuberculin skin test (TST), QuantiFERON TB Gold In-Tube (QFT-G-IT) has gained wide acceptance as a screening strategy for LTB in IBD, although it may be negatively influenced by the prior use of immunomodulators (IMM) such as azathioprine or methotrexate. This study aimed to assess the impact of IMM on the TST and the QFT-G-IT for LTB screening in IBD patients scheduled for anti-TNF therapy. MATERIAL AND METHODS: This observational, prospective, single-center study included consecutive IBD patients scheduled for anti-TNF therapy undergoing on the same day both TST and QFT-G-IT for screening of LTB, between 2008 and 2010. Patients with a prior history of known or suspicious (L)TB receiving (prophylactic) anti-TB therapy were excluded. RESULTS: Seventy-five patients were finally included; 28 were treated with thiopurines (IMM group), while 47 (control group) received either 5 aminosalicylic acid (n = 41) or no therapy (newly diagnosed patients, n = 6). Overall, TST and QFT-G-IT were positive in 14 (18.7%) and 16 (21.3%) patients, respectively. There was no statistically significant difference between the two groups regarding the TST (p = 0.761) and QFT-G-IT (0.572) positivity. The overall concordance between the two tests was moderate (kappa = 0.584), being substantial in the IMM group (kappa = 0.700) and moderate in the control group (kappa = 0.498). CONCLUSION: These preliminary results suggest that IMM may not have a significant impact on either QFT-G-IT or TST, although larger, prospective studies are certainly warranted. PMID- 26139308 TI - Stereotactic navigation and augmented reality for transanal total mesorectal excision? PMID- 26139307 TI - A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. AB - OBJECTIVE: Axial spondyloarthritis (SpA) is a chronic inflammatory disease characterized by back pain and stiffness. The objective of this study was to determine whether golimumab is superior to placebo in patients with nonradiographic axial SpA. METHODS: This phase III, double-blind, randomized, placebo-controlled trial was performed to evaluate subcutaneous golimumab (50 mg) versus placebo in patients ages >=18 years to <=45 years who had active nonradiographic axial SpA according to the Assessment of SpondyloArthritis international Society (ASAS) criteria for <=5 years since diagnosis, high disease activity, and an inadequate response to or intolerance of nonsteroidal antiinflammatory drugs. Patients were randomized 1:1 to receive golimumab or placebo subcutaneously every 4 weeks. The primary end point was 20% improvement according to the ASAS criteria (ASAS20) at week 16. Key secondary end points were an ASAS40 response, ASAS partial remission, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and change in the Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) index for sacroiliac (SI) joint inflammation (SPARCC score). RESULTS: Of the 198 patients randomized, 197 were treated (97 received golimumab, and 100 received placebo). The mean age of the patients was 31 years, and 57.1% were male. At baseline, the mean +/- SD BASDAI was 6.5 +/- 1.5, the mean +/- SD ASDAS was 3.5 +/- 0.9, and the mean +/- SD SPARCC score was 11.3 +/- 14.0. The primary end point, an ASAS20 response, was achieved by significantly more patients in the golimumab group compared with the placebo group (71.1% versus 40.0%; P < 0.0001). An ASAS40 response was also achieved by significantly more patients in the golimumab group compared with the placebo group (56.7% versus 23.0%; P < 0.0001). The incidence of adverse events did not differ meaningfully between groups. CONCLUSION: Patients with active nonradiographic axial SpA treated with golimumab had significantly greater improvement in symptoms compared with patients treated with placebo. Golimumab was well tolerated and had a favorable risk/benefit profile. PMID- 26139309 TI - An integrative population pharmacokinetics approach to the characterization of the effect of hepatic impairment on clobazam pharmacokinetics. AB - An integrative population pharmacokinetics (PPK)-based approach was used to characterize the effect of hepatic impairment on clobazam PK and its major metabolite in systemic circulation, N-desmethylclobazam (N-CLB). At therapeutic clobazam dosages, N-CLB plasma concentrations are 3-5 times greater than the parent compound. PK data from clinical trials in patients with Lennox-Gastaut syndrome (LGS; OV-1002 and OV-1012), healthy participants (OV-1016), and participants with and without renal impairment (OV-1032), as well as those from a publication describing the effects of hepatic impairment on clobazam PK, were merged to create the PPK model. Individual patient clobazam PK parameters from the publication were used to generate patient plasma-concentration data. Clobazam PK was linear and the formation of N-CLB was elimination-rate limited. Hepatic impairment did not affect the total apparent clearance of clobazam but may affect the PK of N-CLB. Because the formation of N-CLB is elimination-rate limited and the total apparent clearance of clobazam is unaffected by hepatic impairment, the PPK model suggests that patients with LGS and hepatic impairment may not require clobazam dosage modification. PMID- 26139310 TI - A stepwise approach to the induction of idiopathic fascicular ventricular tachycardia. AB - PURPOSE: Noninducibility of the clinical tachycardia is a major limitation while mapping and ablating idiopathic fascicular ventricular tachycardia (FVT). There is very little data on systematic induction protocols in this entity. Our aim was to study the role of systematic induction protocols in patients with clinically documented ventricular tachycardia (VT). METHODS: Programmed electrical stimulation was performed at baseline from high right atrium, right ventricular apex, right ventricular outflow tract and from left ventricle as per the protocol. Programmed ventricular stimulation was performed at two drive cycle lengths up to three extrastimuli and short-long-short sequence. If FVT remained non inducible at baseline, pharmacological provocation with isoprenaline/atropine/phenylephrine was used based on the baseline atrio ventricular Wenckebach cycle length. RESULTS: This systematic induction protocol was studied in 68 patients with clinically documented FVT and sustained FVT was inducible in 64 patients (94 %). Of these 64 patients, pharmacological provocation was required in 18 patients (28 %) while in the remaining, sustained VT was induced at baseline. This high induction rate allowed ablation during tachycardia, which resulted in 100 % acute procedural success in the patients where sustained tachycardia could be induced. At a follow up of 29 +/- 13 months, two patients (3 %) had recurrence. CONCLUSIONS: Systematic induction protocol along with the appropriate use of pharmacological agents results in a high induction rate of FVT. This may result in more defined and limited ablation during tachycardia with better success rates and lesser recurrence. PMID- 26139311 TI - The natural history of atrial fibrillation in patients with permanent pacemakers: is atrial fibrillation a progressive disease? AB - OBJECTIVES: Atrial fibrillation (AF) is thought to be a progressive arrhythmia, starting with short paroxysmal episodes, until eventually, it becomes permanent. Evidence for this is limited to studies with short follow-up or with minimal cardiac rhythm monitoring. We utilised the continuous rhythm monitoring capabilities of implanted pacemakers to define better the natural history of AF. METHODS: The study included 356 patients with pacemaker devices capable of continuous atrial rhythm monitoring (186 male, mean age (+/- SD) 79.5 +/- 8.9 years). All clinical records, including history/physical examination reports, laboratory results, ECGs and Holter monitoring data were reviewed. Patients were included if AF episodes >30 s were documented. Permanent pacemaker diagnostic data were reviewed at least every 12 months. ACC/AHA/ESC guidelines were used to define AF episodes as paroxysmal, persistent or long-standing persistent/permanent. RESULTS: Study follow-up period (+/- SD) was 7.2 +/- 3.1 years. Over the study period, 179 of 356 patients (50.3 %) had at least one episode of persistent AF. Of the 356 patients, 314 (88.2 %) had paroxysmal AF and 42 (11.8 %) had persistent AF at the time of diagnosis. The predominant AF subtype, at latest follow-up, was paroxysmal for 192 patients (53.9 %), persistent for 77 (21.6 %) and long-standing persistent/permanent for 87 (24.4 %). Univariable predictors of progression to persistent AF were (1) male gender, (2) increasing left atrial diameter (LAD), (3) reduced atrial pacing (AP) and (4) increasing ventricular pacing. CONCLUSIONS: Although many patients with AF will have persistent episodes, long-term continuous pacemaker follow-up demonstrates that the majority will have a paroxysmal, as opposed to persistent, form of the arrhythmia. PMID- 26139312 TI - Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects. AB - The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Delta(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. PMID- 26139313 TI - A Non-Fatal Self-Poisoning Attempt with Sildenafil. AB - The phosphodiesterase type 5 inhibitor, sildenafil, is not generally known for its use as a self-poisoning drug. However, intoxication cases with lethal outcome have been described. The case presented here is of a 56-year-old man who claimed to have undertaken an unsuccessful suicide attempt by mono-ingestion of 65 tablets of 100 mg sildenafil. He arrived at the emergency department 24 h after intake with severe vomiting and symptoms of blurred vision. Clinical examination revealed no priapism. Of note was a sinus tachycardia of 100 bpm without signs of hypotension. To quantify the sildenafil concentration in serum, an high performance liquid chromatography photo-diode array method was developed and validated according to European Medicines Agency guidelines. The intoxicated patient had a serum concentration of 22.2 ug/mL sildenafil, at the time of presentation, which is far above the therapeutic peak concentration. The serum concentration further declined to 9.2 and 2.3 ug/mL, respectively, 5 and 14 h later, revealing a biological half-life of 4.2 h. To the best of our knowledge, this patient took the highest sildenafil dose, which resulted in the highest serum concentration, ever reported. In this subject, sildenafil showed good tolerability because few symptoms occurred and only moderate supportive therapy was needed for full recovery without sequelae. PMID- 26139314 TI - MDCT assessment of CAD in type-2 diabetic subjects with diabetic neuropathy: the role of Charcot neuro-arthropathy. AB - OBJECTIVES: To compare the CACS and CAD severity assessed by MDCT in neuropathic type-2 diabetic patients with and without Charcot-neuroarthropathy (CN). METHODS: Thirty-four CN asymptomatic-patients and 36 asymptomatic-patients with diabetic neuropathy (DN) without CN underwent MDCT to assess CACS and severity of CAD. Patients were classified as positive for significant CAD in presence of at least one stenosis >50 % on MDCT-coronary-angiography (MDCT-CA). Groups were matched for age, sex and traditional CAD risk-factors. The coronary-angiography (CA) was performed in all patients with at least a significant stenosis detected by MDCT CA, both as reference and eventually as treatment. RESULTS: CN patients showed higher rates of significant CAD in comparison with DN subjects [p < 0.001], while non-significant differences were observed in CACS (p = 0.980). No significant differences were also observed in CACS distribution in all subjects for stenosis >=/<50 % (p = 0.814), as well as in both groups (p = 0.661 and 0.559, respectively). The MDCT-CA showed an overall diagnostic-accuracy for significant CAD of 87%. CONCLUSIONS: These preliminary data suggest that CN-patients have a higher prevalence of severe CAD in comparison with DN-patients, while coronary plaques do not exhibit an increased amount of calcium. MDCT may be helpful to assess the CV risk in such asymptomatic type-2-diabetic patients with autonomic neuropathy. KEY POINTS: Type 2-diabetic-patients with CN result having more severe coronary artery plaque-burden. MDCT-CA may stratify the CV risk in type 2 diabetic-patients with CN. Adequate diagnostic is mandatory for optimal management of type 2-diabetic-patients with CN. PMID- 26139315 TI - Injuries of the scapholunate and lunotriquetral ligaments as well as the TFCC in intra-articular distal radius fractures. Prevalence assessed with MDCT arthrography. AB - OBJECTIVES: To evaluate the prevalence of injuries of the scapholunate and lunotriquetral interosseous ligaments (SLIL, LTIL) as well as the triangular fibrocartilage complex (TFCC) in intra-articular distal radius fractures (iaDRF). METHODS: Two hundred and thirty-three patients with acute iaDRF underwent MDCT arthrography. The SLIL and LTIL were described as normal, partially or completely ruptured. Major injuries of the SLIL were defined as completely ruptured dorsal segments, those of the LTIL as completely ruptured palmar segments. The TFCC was judged as normal or injured. Interobserver variability was calculated. Injury findings were correlated with the types of iaDRF (AO classification). RESULTS: In 159 patients (68.2 %), no SLIL injuries were seen. Minor SLIL injuries were detected in 54 patients (23.2%), major injuries in 20 patients (8.6%). No correlation was found between the presence of SLIL lesions and the types of iaDRF. Minor LTIL injuries were seen in 23 patients (9.9%), major injuries in only 5 patients (2.2%). The TFCC was altered in 141 patients (60.5%). Interobserver variability was high for MDCT arthrography in assessing SLIL and TFC lesions, and fair for LTIL lesions. CONCLUSION: In iaDRF, prevalence of major injuries of the most relevant SLIL is about 9% as evaluated with CT arthrography. KEY POINTS: The C-shaped SLIL is built of dorsal, middle and palmar segments. In iaDRF, major SLIL injuries are associated in 8.6% of the cases. In iaDRF, the SLIL remains intact in 68.3% of the cases. IaDRF and SLIL ruptures can comprehensively be depicted with MDCT arthrography. A three-compartment approach is recommended to assess intrinsic ligaments and the TFCC. PMID- 26139317 TI - Erratum to: Peritumoral apparent diffusion coefficients for prediction of lymphovascular invasion in clinically node-negative invasive breast cancer. PMID- 26139316 TI - Molecular magnetic resonance imaging of atherosclerotic vessel wall disease. AB - Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. KEY POINTS: Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment. PMID- 26139319 TI - Switchable bioelectronics. AB - We review the rapidly emerging field of switchable interfaces and its implications for bioelectronics. We seek to piece together early breakthroughs and key developments, and highlight and discuss the future of switchable bioelectronics by focusing on bio-electrochemical processes based on mimicking and controlling biological environments with external stimuli. All these studies strive to answer a fundamental question: "how do living systems probe and respond to their surroundings? And, following on from that: "how one can transform these concepts to serve the practical world of bioelectronics?" The central obstacle to this vision is the absence of versatile interfaces that are able to control and regulate the means of communication between biological and electronic systems. Here, we review the overall progress made to date in building such interfaces at the level of individual biomolecules and focus on the latest efforts to generate device platforms that integrate bio-interfaces with electronics. PMID- 26139318 TI - 3D quantitative assessment of response to fractionated stereotactic radiotherapy and single-session stereotactic radiosurgery of vestibular schwannoma. AB - OBJECTIVES: To determine clinical outcome of patients with vestibular schwannoma (VS) after treatment with fractionated stereotactic radiotherapy (FSRT) and single-session stereotactic radiosurgery (SRS) by using 3D quantitative response assessment on MRI. MATERIALS: This retrospective analysis included 162 patients who underwent radiation therapy for sporadic VS. Measurements on T1-weighted contrast-enhanced MRI (in 2-year post-therapy intervals: 0-2, 2-4, 4-6, 6-8, 8 10, 10-12 years) were taken for total tumour volume (TTV) and enhancing tumour volume (ETV) based on a semi-automated technique. Patients were considered non responders (NRs) if they required subsequent microsurgical resection or developed radiological progression and tumour-related symptoms. RESULTS: Median follow-up was 4.1 years (range: 0.4-12.0). TTV and ETV decreased for both the FSRT and SRS groups. However, only the FSRT group achieved significant tumour shrinkage (p < 0.015 for TTV, p < 0.005 for ETV over time). The 11 NRs showed proportionally greater TTV (median TTV pre-treatment: 0.61 cm(3), 8-10 years after: 1.77 cm(3)) and ETV despite radiation therapy compared to responders (median TTV pre treatment: 1.06 cm(3); 10-12 years after: 0.81 cm(3); p = 0.001). CONCLUSION: 3D quantification of VS showed a significant decrease in TTV and ETV on FSRT-treated patients only. NR had significantly greater TTV and ETV over time. KEY POINTS: Only FSRT not GK-treated patients showed significant tumour shrinkage over time. Clinical non-responders showed significantly less tumour shrinkage when compared to responders. 3D volumetric assessment of vestibular schwannoma shows advantages over unidimensional techniques. PMID- 26139320 TI - Aptamer-based nanobiosensors. AB - It has been more than two decades since aptamer and the systematic evolution of ligands by exponential enrichment (SELEX) method were discovered by Larry Gold and Andrew Ellington in 1990, respectively. Based on the various advantages of aptamers, they have become a potent rival of antibodies in therapeutics and bio analysis. Especially, the recent advances in aptamer biosensor application are remarkable due to its intrinsic properties of aptamers as nucleic acids and target induced conformational changes, in addition to the introduction of graphene oxide-based easy and simple immobilization-free screening method even for dual aptamers. In addition, the incorporation of various nanomaterials such as metallic nanoparticles, carbon materials, and functional nanospheres in aptasensors has facilitated the improvement of analytical performance and commercial application of aptasensors. In this review, recent prominent reports on aptasensors utilizing nanomaterials were introduced to understand the principle of aptamer-based biosensors and provide an insight for new strategies of aptasensors and the application of various nanomaterials. The perspective on aptamer-based biosensors and diagnostics was also discussed in view of technology and market. PMID- 26139321 TI - Steady-state MRA techniques with a blood pool contrast agent improve visualization of pulmonary venous anatomy and left atrial patency compared with time-resolved MRA pre- and postcatheter ablation in atrial fibrillation. AB - PURPOSE: To compare steady-state magnetic resonance angiography (SS-MRA), using a blood pool contrast agent, with the established technique of time-resolved MRA (TR-MRA), in pulmonary vein mapping and left atrial patency. MATERIALS AND METHODS: Twenty-one patients (12 males, age 58.3 +/- 8.4 years; 9 females; 57 +/- 10 years) undergoing pulmonary vein mapping were evaluated with TR-MRA (TWIST) and SS-MRA. Orthogonal measurements and areas for four veins per patient per technique were assessed by Friedman's test. RESULTS: Overall intertechnique mean difference for any pulmonary vein orthogonal measurement and area was 0.02 +/- 0.34 cm (P = 0.705), and 0.2 +/- 0.08 cm(2) (P < 0.001). Interobserver correlation was strong for diameter and area measurements using the three methods with a range of 0.72-0.94, and 0.87-0.97, respectively. Left atrial appendage image quality score for TR-MRA was significantly lower than the other two methods (P < 0.001). Both observers detected more stenosis on inversion recovery (IR) True FISP compared to TR-MRA and IR-FLASH. CONCLUSION: SS-MRA with a blood pool agent compared favorably to the established technique of TR-MRA for quantitative assessment of pulmonary venous anatomy. SS-MRA offers greater spatial resolution than TR-MRA with increased confidence for ruling out left atrial appendage filling defect. PMID- 26139322 TI - Analysis of reasons for sow culling and seasonal effects on reproductive disorders in Southern China. AB - Sow culling rates have a direct correlation to the economic efficiency of both breeding herd and commercial herd. Analyzing the reasons of sow culling could lead to improve production efficiency of farms. This study, which involved inspections of four farms in Southern China, manifested that the rate of unplanned sow-culling has reached to 78.1% in total culls. In which, reproductive disorders and lameness accounted for 35.3% and 22.5%, respectively. The average parity of culled sows was 4.9, but a high proportion (19.6%) of sows was culled at their first parity. Anestrus, the highest proportion of reproductive disorders, accounting for 47.7%, occurred in July followed by June (17.7% and 11.8% respectively). The frequency of culling due to reproductive disorders in Southern China was higher than others regions, which suffered from the high temperature and humidity in Southern China. The frequency of sow culling reached its peak in the summer, specifically in July (12.3%), which means that hot weather has an adverse effect on sow culling. Pig farmers should take effective measures to reduce heat stress as nutrition strategies or cooling systems in gestation and/or farrowing sow herds between May and July in Southern China. PMID- 26139324 TI - Hair and Scalp Manifestations in Secondary Syphilis: Epidemiology, Clinical Features and Trichoscopy. AB - BACKGROUND: Syphilitic alopecia (SA) is mainly described in single case reports, and there are only a few epidemiological studies. OBJECTIVE: To investigate the clinical and dermoscopic features of SA in patients with secondary syphilis and to record its actual prevalence. METHODS: All patients with a diagnosis of secondary syphilis were clinically and trichoscopically evaluated in search of hair and scalp alterations. RESULTS: Five of 12 patients (41.6%) diagnosed with secondary syphilis had SA. The 'moth-eaten' pattern was detected in 4 patients (80% of cases): 1 had 'essential' SA, whereas 3 patients had 'symptomatic' SA. The 'diffuse' SA pattern was found in 1 patient. Trichoscopy of the 'moth-eaten' areas showed that alopecia is mainly due to a reduction in the number of terminal hairs. One patient with secondary syphilis showed trichodynia that regressed completely after antibiotic therapy. LIMITATIONS: The small number of patients included and the fact that none of our patients accepted to be biopsied in an affected area. CONCLUSION: Since SA appears to be present much more frequently than reported in the literature, when secondary syphilis is suspected, the patient should be examined for the presence of signs compatible with SA and the scalp should be examined by dermoscopy. PMID- 26139323 TI - Kidney measures with diabetes and hypertension on cardiovascular disease: the Atherosclerosis Risk in Communities Study. AB - BACKGROUND: Whether the association of chronic kidney disease (CKD) with cardiovascular risk differs based on diabetes mellitus (DM) and hypertension (HTN) status remains unanswered. METHODS: We investigated 11,050 participants from the Atherosclerosis Risk in Communities Study (fourth examination (1996 1998)) with follow-up for cardiovascular outcomes (coronary disease, heart failure and stroke) through 2009. Using the Cox regression models, we quantified cardiovascular risk associated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) in individuals with and without DM and/or HTN and assessed their interactions. RESULTS: Individuals with DM and HTN generally had higher cardiovascular risk relative to those without at all the levels of eGFR and ACR. Cardiovascular risk increased with lower eGFR and higher ACR regardless of DM and HTN status (e.g. adjusted hazards ratio (HR) for eGFR 30 44 vs. 90-104 ml/min/1.73 m(2), 2.32 (95% CI, 1.66-3.26) in non-diabetics vs. 1.83 (1.25-2.67) in diabetics and 2.45 (2.20-5.01) in non-hypertensives vs. 1.51 (1.27-1.81) in hypertensives and corresponding adjusted HR for ACR 30-299 vs. <10 mg/g, 1.70 (1.45-2.00) vs. 1.34 (1.10-1.64) and 1.42 (1.10-1.85) vs. 1.57 (1.36 1.81), respectively). Only the ACR-DM interaction reached significance, with a shallower relative risk gradient among diabetics than among non-diabetics (p = 0.02). Analysis of individual cardiovascular outcomes showed similar results. CONCLUSION: Although individuals with DM and HTN generally had higher cardiovascular risk relative to those without these complications, both low eGFR and high ACR were associated with cardiovascular diseases regardless of the presence or absence of DM and HTN. These findings reinforce the importance of CKD in cardiovascular outcomes. PMID- 26139325 TI - Somatic mutational landscape of AML with inv(16) or t(8;21) identifies patterns of clonal evolution in relapse leukemia. PMID- 26139326 TI - Factors associated with clinical decision-making in relation to treatment need for temporomandibular disorders. AB - OBJECTIVE: The aim of this study was to analyze dentist's clinical decision making related to treatment need for temporomandibular disorders (TMD) in an adult population. MATERIALS AND METHODS: The study population comprised 779 randomly selected 35, 50, 65 and 75 year old individuals living in the county of Vasterbotten, Sweden. The participants filled out a questionnaire and were examined clinically according to a structured protocol. The four examiners (two men, two women) were experienced dentists and were calibrated before the start of the study. After examination they individually assessed the need of treatment owing to TMD. RESULTS: In total, 15% of the study population was considered to have a treatment need owing to TMD. The highest estimate was noted for 35 and 50 years old women and the lowest for 65 and 75 years old men. Overall, 21% of the women and 8% of the men were considered to have a treatment need owing to TMD, with statistically significant differences between men and women for the 35 and 50 years old groups. Inter-individual variations in dentists' decisions were observed. In a multivariate analysis, female gender, signs and symptoms of TMD pain, signs and symptoms of TMD dysfunction and smoking were associated with estimated treatment need. CONCLUSIONS: The prevalence of estimated treatment need owing to TMD was fairly high, but the dentists' clinical decision-making process showed large inter-individual variability. The observation calls for further research on the factors affecting the decision-making process in care providers. PMID- 26139327 TI - Efficient Synthesis of Differentiated syn-1,2-Diol Derivatives by Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of alpha-Alkoxy-Substituted beta-Ketoesters. AB - Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl alpha-alkoxy-beta-ketoesters in the presence of well-defined, commercially available, chiral catalyst Ru(II) -(N-p-toluenesulfonyl-1,2 diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn alpha-alkoxy-beta hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99 %). Additionally, after extensive screening of the reaction conditions, the use of Ru(II) - and Rh(III) -tethered precatalysts extended this process to more-challenging substrates that bore alkenyl-, alkynyl-, and alkyl substituents to provide the corresponding syn alpha-alkoxy-beta-hydroxyesters with excellent enantiocontrol (up to 99 % ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl) propanoate, which is an important pharmacophore in a number of peroxisome proliferator-activated receptor alpha/gamma dual agonist advanced drug candidates used for the treatment of type-II diabetes. PMID- 26139328 TI - Response to "Influence of Age and HLA Alleles on the CMV-Specific Cell-Mediated Immunity Among CMV-Seropositive Kidney Transplant Candidates". PMID- 26139329 TI - Social shaping of voices does not impair phenotype matching of kinship in mandrills. AB - Kin selection theory provides a strong theoretical framework to explain the evolution of altruism and cooperative behaviour among genetically related individuals. However, the proximate mechanisms underlying kin discrimination, a necessary process to express kin-related behaviour, remain poorly known. In particular, no study has yet unambiguously disentangled mechanisms based on learned familiarity from true phenotype matching in kin discrimination based on vocal signals. Here we show that in addition to genetic background, social accommodation also shapes individual voices in an Old World monkey (Mandrillus sphinx), even though primate vocalizations were thought to be innate and little flexible. Nonetheless, social shaping of voice parameters does not impair kin discrimination through phenotype-matching of unknown relatives, revealing unexpected discriminatory versatility despite signal complexity. Accurate signal production and perception, therefore, provide a basis for kin identification and kin-biased behaviour in an Old World primate. PMID- 26139330 TI - Perioperative anaphylaxis: what should be known? AB - Perioperative anaphylaxis is a unique condition as a result of the additive cardiovascular effects of anesthetics on the cardiovascular disturbances of anaphylaxis. It occurs mainly in adulthood, primarily follows anesthetic induction, and for the most part, is an IgE-mediated pathomechanism. Neuromuscular blocking agents (NMBAs) and antibiotics are the main culprit drugs, while latex is now infrequently involved. The Ring and Messmer scale is a useful tool for demonstrating the clinical severity of perioperative immediate hypersensitivity and guiding its management. Grades III and IV are life threatening and are referred to as anaphylaxis. Three different clinical patterns of grade III may be observed, where cardiovascular collapse is the cardinal sign. Grade IV presents as cardiac arrest. The initial diagnosis is presumptive, whereas the etiological assessment is linked to the clinical presentation, tryptase levels, and skin test results. Since anaphylaxis presents with significant hypovolemia and vasoplegia, aggressive fluid therapy and epinephrine are the cornerstones of management. Whenever possible, anesthetic discontinuation is also recommended. Scientific evidence in favor of preemptive therapeutic strategies to prevent anaphylaxis in the operative setting is lacking. PMID- 26139331 TI - Is clinical tolerance possible after allergen immunotherapy? AB - There is a growing evidence that allergen immunotherapy (AIT) can provide significant and long-lasting clinical benefit for a number of allergic individuals. However, it is less clear if AIT results in clinical tolerance, which is characterized by a persistent state of clinical non-reactivity to allergens after therapy is finished. Addressing this knowledge gap is particularly relevant for patients undergoing AIT for food allergies, as anything less than complete tolerance could have potentially devastating consequences. An increasing number of studies, in particular those involving oral immunotherapy, are attempting to assess tolerance induction following AIT. Clinical tolerance does appear to be achievable in a subset of patients undergoing AIT, but whether this is equivalent to the type of tolerance observed in nonallergic individuals remains unknown. Developing established criteria for assessing tolerance induction, as well as the use of consistent terminology when describing clinical tolerance, will be important for determining the disease-modifying potential of AIT. PMID- 26139332 TI - Microbiota metabolite regulation of host immune homeostasis: a mechanistic missing link. AB - Metazoans predominantly co-exist with symbiotic microorganisms called the microbiota. Metagenomic surveys of the microbiota reveal a diverse ecosystem of microbes particularly in the gastrointestinal (GI) tract. Perturbations in the GI microbiota in higher mammals (i.e., humans) are linked to diseases with variegated symptomology including inflammatory bowel disease, asthma, and auto inflammatory disorders. Indeed, studies using germ-free mice (lacking a microbiota) confirm that host development and homeostasis are dependent on the microbiota. A long-known key feature of the GI tract microbiota is metabolizing host indigestible dietary matter for maximum energy extraction; however, host signaling pathways are greatly influenced by the microbiota as well. In line with these observations, recent research has revealed that metabolites produced strictly by select microbiota members are mechanistic regulators of host cell functions. In this review, we discuss two major classes of microbiota-produced metabolites: short-chain fatty acids and tryptophan metabolites. We describe the known important roles for these metabolites in shaping host immunity and comment on the current status and future directions for microbiota metabolomics research. PMID- 26139333 TI - Cutaneous and systemic mastocytosis in children: a risk factor for anaphylaxis? AB - Childhood mastocytosis is usually a clonal mast cell disease related to activating mutations in KIT. The symptoms in childhood mastocytosis are typically cutaneous in nature although systemic symptoms including anaphylaxis due to the release of mast cells (MC) mediators can also manifest. The prevalence of anaphylaxis reported in childhood mastocytosis is higher than the rates reported in the pediatric general population, but lower than the prevalence of anaphylaxis described in adult mastocytosis. An extensive cutaneous involvement was reported as a risk factor for anaphylaxis, and patients with diffuse cutaneous mastocytosis have been documented to have more severe anaphylaxis symptoms. Anaphylaxis due to unknown causes or idiopathic anaphylaxis was the primary etiology in pediatric mastocytosis, followed by foods as the most relevant identified trigger; however, hymenoptera stings are not a frequent trigger of anaphylaxis in children with mastocytosis in contrast to the adult patients. PMID- 26139334 TI - Update on systemic sclerosis. AB - Systemic sclerosis (SSc) is a rare autoimmune disease characterized by autoantibody production, small-vessel vasculopathy, and skin and other organ fibrosis. The disease is clinically heterogeneous with most patients having some degree of skin sclerosis with varying organ system involvement. Early disease can be difficult to diagnose, especially with minimal skin sclerosis and absence of anti-nuclear antibody (ANA) positivity; however, studies have demonstrated early diagnosis is important as early treatment could potentially lead to better outcomes. New classification criteria have recently been published that have higher sensitivity for detecting early disease thus allowing for a broader spectrum of patients to be represented in clinical trials. Treatment guidelines have been published based on a limited number of randomized-controlled clinical trials; however, there are ongoing phase II and III clinical trials with novel agents that are promising and will change the treatment landscape over the next decade. PMID- 26139335 TI - Anaphylaxis to insect venom allergens: role of molecular diagnostics. AB - Anaphylaxis due to Hymenoptera stings is one of the most severe consequences of IgE-mediated hypersensitivity reactions. Although allergic reactions to Hymenoptera stings are often considered as a general model for the underlying principles of allergic disease, diagnostic tests are still hampered by a lack of specificity and venom immunotherapy by severe side effects and incomplete protection. In recent years, the knowledge about the molecular composition of Hymenoptera venoms has significantly increased and more and more recombinant venom allergens with advanced characteristics have become available for diagnostic measurement of specific IgE in venom-allergic patients. These recombinant venom allergens offer several promising possibilities for an improved diagnostic algorithm. Reviewed here are the current status, recent developments, and future perspectives of molecular diagnostics of venom allergy. Already to date, it is foreseeable that component-resolution already has now or will in the future have the potential to discriminate between clinically significant and irrelevant sensitization, to increase the specificity and sensitivity of diagnostics, to monitor immunotherapeutic intervention, and to contribute to the understanding of the immunological mechanisms elicited by insect venoms. PMID- 26139336 TI - Biofilm formation and extracellular polymeric substances (EPS) production by Bacillus subtilis depending on nutritional conditions in the presence of polyester film. AB - The influence of biofilm formation as the mode of microorganism growth on degradation of synthetic polymers represents an important research topic. This study focuses on the effect of biofilm developed by Bacillus subtilis (BS) cultivated submerged under various nutrition conditions on biodeterioration of poly(epsilon-caprolactone) film. Polymer in the film form (thickness 0.7 mm) was incubated for 21 days either continuously or by regularly renewed system. The scission of polyester chain bonds took place in all biotic media and was enhanced by biofilm formation in nutrient-rich media. PMID- 26139337 TI - Male-to-Female Genital Reassignment Surgery: A Retrospective Review of Surgical Technique and Complications in 60 Patients. AB - BACKGROUND: Patients with male-to-female gender dysphoria (GD) require multidisciplinary assessment and management. Nowadays, more and more patients decide to undergo genital reassignment surgery (GRS) to have aesthetic and functional external female genitalia. Different techniques of this procedure have been described. Orchiectomy, penile disassembly, creation of a neovaginal cavity, repositioning of urethral meatus, and clitorolabioplasty may be identified as the five major steps in all of these techniques. METHODS: We conducted a retrospective study of 60 patients who underwent genital reassignment procedure for male-to-female GD at our department between November 2008 and August 2013 with a minimum follow-up of 1 year. Data were collected on surgical technique, postoperative dilations protocol, complications, and functional and aesthetic outcomes. We describe and critically evaluate the surgical technique used in our department. RESULTS: Follow-up ranged from 14 to 46 months. Two patients developed late neovaginal stricture, and two patients experienced rectovaginal fistulae (one required surgical revision with dermal porcine graft placement). Minor complications occurred in 13 patients and included urethral stenosis, partial wound dehiscence, and minor bleeding. Secondary aesthetic revision surgery was performed in 13 cases. CONCLUSIONS: GRS can provide good functional and aesthetic outcomes in patients with male-to-female GD. However, despite a careful planning and meticulous surgical technique, secondary procedures are frequently required to improve the function and appearance of the neovagina. PMID- 26139338 TI - Impact of BMI Variations on Survival in Elderly Hemodialysis Patients. AB - OBJECTIVES: In elderly hemodialysis patients, protein-energy wasting is associated with poor outcome; however, the association between body mass index (BMI) changes over time, and survival has been seldom studied in this particularly frail population. DESIGN AND METHODS: This prospective study recruited 502 hemodialysis patients aged >=75 years from the French cohort ARNOS and followed them from 2005 to 2009. BMI changes over time were modeled by individual linear regression models. Survival analyses used frailty Cox models. RESULTS: The population average age was 80.9 years. Forty-one percent of the patients died during follow-up. A 1 kg/m(2) lower baseline BMI was associated with a 4% increase in the risk of death over the study period (hazard ratio [HR] 1.04, 95% confidence interval [1.01-1.08], P = .02). A 5% BMI loss per year was associated with a 52% increase in the risk of death (HR 1.52, 95% confidence interval [1.32-1.75], P < .001). In patients who lost weight (>5% BMI loss per year), the lower was the baseline BMI, the higher was the HR for death. There was a similar trend in the patients with stable weight (5% BMI loss-5% BMI gain per year). In patients who gained weight, the HR was unexpectedly higher than in those with stable weight. CONCLUSIONS: In elderly hemodialysis patients, the impact of the BMI percent change on survival was stronger than that of the baseline BMI. Patients with stable weight had longer survivals than patients who lost or gained weight. Thus, in this population, BMI changes should be regularly assessed. Further studies should assess the safety of weight gain strategies. PMID- 26139339 TI - Effects of dalfampridine on multi-dimensional aspects of gait and dexterity in multiple sclerosis among timed walk responders and non-responders. AB - BACKGROUND: Dalfampridine extended release 10mg tablets (D-ER) have demonstrated improvement in walking for ambulatory persons with multiple sclerosis (pwMS), termed "responders." OBJECTIVE: This study examined the extent additional aspects of gait and dexterity change for patients prescribed D-ER. METHODS: Over 14 weeks, walking endurance, dynamic gait, self-report walking ability and fine and gross dexterity were examined in pwMS prescribed D-ER as a part of routine clinical care. RESULTS: The final results (n=39) validate that a subset of pwMS improve walking speed (Time 25-Foot Walk Test, p<0.0001). Significant improvements in gait and dexterity were observed even among participants who did not improve walking speed. Improvements were evident in gait and dexterity domains including Six Minute Walk Test, p=0.007, Six-Spot Step Test, p<0.0001, Multiple Sclerosis Walking Scale-12, p<0.0001, Nine Hole Peg Test, p<0.0001 dominant and non-dominant sides, and Box and Blocks Test, p=0.005 and 0.002, dominant and non-dominant sides, respectively. CONCLUSIONS: These findings suggest that D-ER may be a potential treatment for gait impairments, beyond walking speed and dexterity in pwMS. Further investigation regarding D-ER response is warranted. PMID- 26139340 TI - Chemosensory disturbances-associated nanocholinergic dysfunction: The case of, not only, myasthenia gravis. PMID- 26139341 TI - Art and dystonia. AB - Dystonia has a recent history in medicine. Focal dystonia was described in the 19th century by classic authors including Gowers, whilst generalized dystonia was described at the turn of the century. However, it is possible to find precise descriptions of dystonia in art, centuries before the medical definition. We have reviewed several pieces of art (sculpture, painting and literature) across the history that might represent descriptions of dystonia, from ancient period to nowadays. In classic times, the first reference to abnormal postures can be tracked back to the new Empire of Egypt (equinus foot), not to mention some recently described examples of dystonia from the Moche sculptures in Peru or Veracruz culture from Mexico. In Middle Ages it is possible to find many examples of sculptures in European cathedrals representing peasants with dramatic, presumably dystonic postures that coexist with amputation of limbs. This unique combination of dystonia and limb amputation probably represents ergotism. The painters Brueghel, Ribera and Velazquez also represented figures with postures likely to be dystonic. Literature is also a source of precise pre-neurological descriptions, especially during the 19th century. In David Copperfield, Dickens depicts characters with generalized dystonia (Uriah Heep), cervical dystonia (Mr. Sharp) and spasmodic dysphonia (Mr Creakle). Finally, even in modern Art (19th and 20th centuries), there are dramatic descriptions of abnormal postures that are likely to be dystonic, such as painful cervical dystonia (Brancusi), cervical dystonia with sensory trick (Modigliani) and upper limb dystonia (Wyspianski). However some postures presented in works of art may simply be a form of artistic expression and only bear unintentional resemblance to the dystonic postures. Art may be a source of neurological information, and that includes primary and secondary dystonia. PMID- 26139342 TI - Comparison of uroflow parameters in children with pure constipation versus constipation plus lower urinary tract symptoms. AB - OBJECTIVE: The aim of this study was to compare uroflow parameters of patients with pure constipation against those with constipation plus lower urinary tract symptoms (LUTS) and a control group (no constipation). MATERIALS AND METHODS: During August 2012 to March 2014 three groups of patients were enrolled into the study: group C (constipation only), group CL (LUTS plus constipation) and group N (control: no constipation or LUTS). Dysfunctional elimination syndrome (DES) scores, uroflowmetry/electromyography (uroflow-EMG) findings, postvoiding residual urine (PVR) and rectal diameter were measured and compared between groups. RESULTS: Groups C, CL and N comprised 80, 100 and 30 patients, respectively. Average DES scores were 12.6, 18.7 and 4.9, respectively. Voided volume (as a percentage of expected bladder capacity) was 104%, 89% and 101%; and average maximum flow rate was 21.1 ml/s, 36.4 ml/s and 28.1 ml/s, respectively. Pelvic floor muscle activity during voiding was seen in 40.0%, 42.0% and 6.7% of patients in groups C, CL and N, respectively; and pathological PVR was seen in 26.3%, 55.0% and 3.3% of patients in the respective groups. Average rectal diameter was measured as 38.6 mm, 36.4 mm and 28.1 mm in groups C, CL and N, respectively. CONCLUSION: This study found that abnormal voiding parameters are present in patients with constipation even if LUTS are not present. Therefore, it is important that all patients presenting with constipation have their voiding function evaluated. PMID- 26139343 TI - Learned vocal and breathing behavior in an enculturated gorilla. AB - We describe the repertoire of learned vocal and breathing-related behaviors (VBBs) performed by the enculturated gorilla Koko. We examined a large video corpus of Koko and observed 439 VBBs spread across 161 bouts. Our analysis shows that Koko exercises voluntary control over the performance of nine distinctive VBBs, which involve variable coordination of her breathing, larynx, and supralaryngeal articulators like the tongue and lips. Each of these behaviors is performed in the context of particular manual action routines and gestures. Based on these and other findings, we suggest that vocal learning and the ability to exercise volitional control over vocalization, particularly in a multimodal context, might have figured relatively early into the evolution of language, with some rudimentary capacity in place at the time of our last common ancestor with great apes. PMID- 26139344 TI - Seasonal variation in attention and spatial performance in a wild population of the African striped mouse (Rhabdomys pumilio). AB - Cognitive flexibility describes the reversible changes of cognition in response to environmental changes. Although various environmental factors such as temperature, photoperiod and rainfall change seasonally, seasonal variation in cognitive performance has been reported in merely a few birds and mammals. We assessed whether cognitive performance in a wild population of African striped mice Rhabdomys pumilio, from the Succulent Karoo semidesert of South Africa, differed between summer and winter. In order to measure cognitive performance, striped mice were trapped in the field, tested under laboratory conditions at our research station and returned to the field within 5 h. We measured attention and spatial memory using the standardized orientation response test and the Barnes maze test. Males tested during summer oriented faster toward a predator-stimulus but made more errors and took longer to locate a shelter than males tested during winter. In contrast, females' performance did not differ between the two seasons. We discuss how the faster orientation in males during winter might be the consequence of lower temperatures and/or prolonged food restriction. We suggest that the enhancement of spatial performance during winter might be due to a greater motivation for future dispersal in male striped mice, as spring represents the breeding season. PMID- 26139345 TI - Extended conformation of the proline-rich domain of human aryl hydrocarbon receptor-interacting protein-like 1: implications for retina disease. AB - Mutations in the primate-specific proline-rich domain (PRD) of aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) are thought to cause Leber congenital amaurosis or dominant cone-rod dystrophy. The role of PRD and the mechanisms of PRD mutations are poorly understood. Here, we have examined properties of hAIPL1 and effects of the PRD mutations on protein structure and function. Solution structures of hAIPL1, hAIPL11-316 with PRD truncation, and the P351Delta12 and P376S mutants were examined by small angle X-ray scattering. Our analysis suggests that PRD assumes an extended conformation and does not interact with the FK506-binding and tetratricopeptide domains. The PRD truncation, but not PRD mutations, reduced the molecule's radius of gyration and maximum dimension. We demonstrate that hAIPL1 is a monomeric protein, and its secondary structure and stability are not affected by the PRD mutations. PRD itself is an extended monomeric random coil. The PRD mutations caused little or no changes in hAIPL1 binding to known partners, phosphodiesterase-6A and HSP90. We also identified the gamma-subunit of phosphodiesterase-6 as a novel partner of hAIPL1 and hypothesize that this interaction is altered by P351Delta12. Our results highlight the complexity of mechanisms of PRD mutations in disease and the possibility that certain mutations are benign variants. Mutations in the proline-rich domain (PRD) of human AIPL1 cause severe retinal diseases, yet the role of PRD and the mechanisms of PRD mutations are unknown. Here, we describe a SAXS-derived solution structure of AIPL1 and functional properties of disease-linked AIPL1-PRD mutants. This structure and functional analyses provide a framework for understanding the mechanisms of PRD in disease. PMID- 26139347 TI - Switching plasmon coupling through the formation of dimers from polyaniline coated gold nanospheres. AB - Active modulation of the plasmon coupling in homodimers of polyaniline (PANI) coated Au nanospheres is achieved by changing the proton-doping state of the PANI shell. Such a PANI-enabled modulation of the plasmon coupling in the dimers gives rise to remarkable spectral shifts, which show an exponential dependence on the interparticle gap distance. For the dimer with a 10 nm PANI shell thickness and a 0.5 nm gap distance, the shift of the stronger scattering peak in response to the active modulation reaches 231 nm. Electrodynamic simulations reveal that the shift of the dipolar bonding plasmon mode dominates the position variation of the stronger scattering peak for the dimers with different gap distances. Moreover, the quadrupolar bonding plasmon mode can be turned on and off by controlling the proton-doping state of the dimers with gap distances of less than ~3 nm. These results are of high importance for fundamentally understanding the sensitivity of coupled plasmon resonance modes to the dielectric environment, as well as for designing active plasmonic devices with high modulation performances. PMID- 26139348 TI - Interfacing proteins with graphitic nanomaterials: from spontaneous attraction to tailored assemblies. AB - This critical review aims at giving insights on the spontaneous tendency of proteins and their constitutive parts to adsorb on graphitic nanomaterials (GNMs) through non-covalent interactions occurring at their interfaces. Specifically, it focuses on the theoretical and experimental studies carried out to comprehend in depth the forces ruling the adsorption processes of proteins on fullerene, carbon nanotubes and graphene. In a systematic way the reader is guided through the most recent and representative examples describing at the atomistic level of detail the structural modalities and the chemico-physical principles through which amino acids, polypeptides and folded proteins interact with GNMs' surface, thereby taking into consideration the mutual effects of both protein structural complexity and nanomaterial topology. Based on their chemical and structural features, the study and understanding of the protein-nanomaterial interfaces can be exploited in the view of design and control the spontaneous formation of biologically-active hybrid materials for the development of new tailored applications in the field of sensing, nanomedicine and biochemistry. PMID- 26139346 TI - Arabidopsis MAS2, an Essential Gene That Encodes a Homolog of Animal NF-kappa B Activating Protein, Is Involved in 45S Ribosomal DNA Silencing. AB - Ribosome biogenesis requires stoichiometric amounts of ribosomal proteins and rRNAs. Synthesis of rRNAs consumes most of the transcriptional activity of eukaryotic cells, but its regulation remains largely unclear in plants. We conducted a screen for ethyl methanesulfonate-induced suppressors of Arabidopsis thaliana ago1-52, a hypomorphic allele of AGO1 (ARGONAUTE1), a key gene in microRNA pathways. We identified nine extragenic suppressors as alleles of MAS2 (MORPHOLOGY OF AGO1-52 SUPPRESSED2). Positional cloning showed that MAS2 encodes the putative ortholog of NKAP (NF-kappa B activating protein), a conserved eukaryotic protein involved in transcriptional repression and splicing in animals. The mas2 point mutations behave as informational suppressors of ago1 alleles that cause missplicing. MAS2 is a single-copy gene whose insertional alleles are embryonic lethal. In yeast two-hybrid assays, MAS2 interacted with splicing and ribosome biogenesis proteins, and fluorescence in situ hybridization showed that MAS2 colocalizes with the 45S rDNA at the nucleolar organizer regions (NORs). The artificial microRNA amiR-MAS2 partially repressed MAS2 and caused hypomethylation of 45S rDNA promoters as well as partial NOR decondensation, indicating that MAS2 negatively regulates 45S rDNA expression. Our results thus reveal a key player in the regulation of rRNA synthesis in plants. PMID- 26139349 TI - Deterministic Domain Wall Motion Orthogonal To Current Flow Due To Spin Orbit Torque. AB - Spin-polarized electrons can move a ferromagnetic domain wall through the transfer of spin angular momentum when current flows in a magnetic nanowire. Such current induced control of a domain wall is of significant interest due to its potential application for low power ultra high-density data storage. In previous reports, it has been observed that the motion of the domain wall always happens parallel to the current flow - either in the same or opposite direction depending on the specific nature of the interaction. In contrast, here we demonstrate deterministic control of a ferromagnetic domain wall orthogonal to current flow by exploiting the spin orbit torque in a perpendicularly polarized Ta/CoFeB/MgO heterostructure in presence of an in-plane magnetic field. Reversing the polarity of either the current flow or the in-plane field is found to reverse the direction of the domain wall motion. Notably, such orthogonal motion with respect to current flow is not possible from traditional spin transfer torque driven domain wall propagation even in presence of an external magnetic field. Therefore the domain wall motion happens purely due to spin orbit torque. These results represent a completely new degree of freedom in current induced control of a ferromagnetic domain wall. PMID- 26139351 TI - Tumour immunology: Stressed DCs can't handle T cells. PMID- 26139352 TI - The effect of pulse train profile on the efficacy of pulsed-dye laser treatments for port-wine stains. PMID- 26139350 TI - Eicosanoid storm in infection and inflammation. AB - Controlled immune responses to infection and injury involve complex molecular signalling networks with coordinated and often opposing actions. Eicosanoids and related bioactive lipid mediators derived from polyunsaturated fatty acids constitute a major bioactive lipid network that is among the most complex and challenging pathways to map in a physiological context. Eicosanoid signalling, similar to cytokine signalling and inflammasome formation, has primarily been viewed as a pro-inflammatory component of the innate immune response; however, recent advances in lipidomics have helped to elucidate unique eicosanoids and related docosanoids with anti-inflammatory and pro-resolution functions. This has advanced our overall understanding of the inflammatory response and its therapeutic implications. The induction of a pro-inflammatory and anti inflammatory eicosanoid storm through the activation of inflammatory receptors by infectious agents is reviewed here. PMID- 26139353 TI - Fusion with human lung cancer cells elongates the life span of human umbilical endothelial cells and enhances the anti-tumor immunity. AB - PURPOSE: Human umbilical endothelial cells (HUVECs) have been proved as an effective whole-cell vaccine inhibiting tumor angiogenesis. However, HUVECs divide a very limited number of passages before entering replicative senescence, which limits its application for clinical situation. Here, we fused HUVECs with human pulmonary adenocarcinoma cell line A549s and investigated the anti-tumor immunity of the hybrids against mice Lewis lung cancer. METHODS: HUVECs were fused with A549s using polyethylene glycol and were sorted by flow cytometry. The fusion cells (HUVEC-A549s) were confirmed by testing the expression of telomerase and VE-cadherin, the senescence-associated beta-galactosidase activity, and tube formation ability. HUVEC-A549s were then irradiated and injected into the C57BL/6 mice of protective, therapeutic, and metastatic models. The mechanism of the anti tumor immunity was explored by analyzing mice sera, spleen T lymphocytes, tumor microenvironment, and histological changes. RESULTS: HUVEC-A549s coexpressed tumor and endothelial markers and maintained the vascular function of tube forming at passage 30 without showing signs of senescence. HUVEC-A549s could induce protective and therapeutic anti-tumor activity for LL(2) model and presented stronger activity against metastasis than HUVECs. Both humoral and cellular immunity were participated in the anti-angiogenic activity, as HUVECs neutralizing IgG and HUVECs-toxic lymphocytes were increased. Angiogenic mediators (VEGF and TGF-beta) and tumor microenvironment cells MDSCs and Tregs were also diminished. CONCLUSIONS: Our findings might provide a novel strategy for HUVECs-related immunotherapy, and this vaccine requires lower culture condition than primary HUVECs while enhancing the anti-tumor immunity. PMID- 26139354 TI - Prediction of Locally Advanced Urothelial Carcinoma of the Bladder Using Clinical Parameters before Radical Cystectomy--A Prospective Multicenter Study. AB - INTRODUCTION: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. MATERIALS AND METHODS: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. RESULTS: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p < 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p < 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p < 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. CONCLUSION: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters. PMID- 26139355 TI - Building knowledge requires bricks, not sand: The critical role of familiar constituents in learning. AB - Despite vast efforts to better understand human learning, some principles have been overlooked; specifically, that less familiar stimuli are more difficult to combine to create new knowledge and that this is because less familiar stimuli consume more working memory resources. Participants previously unfamiliar with Chinese characters were trained to discriminate visually similar characters during a visual search task over the course of a month, during which half of the characters appeared much more frequently. Ability to form associations involving these characters was tested via cued recall for novel associations consisting of two Chinese characters and an English word. Each week performance improved on the cued-recall task. Crucially, however, even though all Chinese character pairs were novel each week, those pairs consisting of more familiar characters were more easily learned. Performance on a working-memory task was better for more familiar stimuli, consistent with the claim that familiar stimuli consume fewer working memory resources. These findings have implications for optimal instruction, including second language learning. PMID- 26139356 TI - Effects of strategy on visual working memory capacity. AB - Substantial evidence suggests that individual differences in estimates of working memory capacity reflect differences in how effectively people use their intrinsic storage capacity. This suggests that estimated capacity could be increased by instructions that encourage more effective encoding strategies. The present study tested this by giving different participants explicit strategy instructions in a change detection task. Compared to a condition in which participants were simply told to do their best, we found that estimated capacity was increased for participants who were instructed to remember the entire visual display, even at set sizes beyond their capacity. However, no increase in estimated capacity was found for a group that was told to focus on a subset of the items in supracapacity arrays. This finding confirms the hypothesis that encoding strategies may influence visual working memory performance, and it is contrary to the hypothesis that the optimal strategy is to filter out any items beyond the storage capacity. PMID- 26139357 TI - The moral experience of illness and its impact on normalisation: Examples from narratives with Punjabi women living with rheumatoid arthritis in the UK. AB - The moral component of living with illness has been neglected in analyses of long term illness experiences. This article attempts to fill this gap by exploring the role of the moral experience of illness in mediating the ability of those living with a long-term condition (LTC) to normalise. This is explored through an empirical study of women of Punjabi origin living with rheumatoid arthritis (RA) in the UK. Sixteen informants were recruited through three hospitals in UK cities and interviews conducted and analysed using a grounded theory approach. The intersection between moral experience and normalisation, within the broader context of ethnic, gender and socioeconomic influences, was evident in the following: disruption of a core lived value (the centrality of family duty), beliefs about illness causation affecting informants' 'moral career', and perceived discrimination in the workplace. The data illustrate the importance of considering an ethnic community's specific values and beliefs when understanding differences in adapting to LTCs and changing identities. PMID- 26139358 TI - Is the search for right-to-left shunt still worthwhile? AB - OBJECTIVES: Patent foramen ovale (PFO) is a common disembryogenic defect with well-attested prevalence but dubious etiopathogenetic linkage with cryptogenic stroke and different clinical conditions. Transcranial color-coded Doppler (TCCD) assures high accuracy in diagnosing right-to-left shunt (RLS) and its functional aspects. Aim of the study was to evaluate RLS prevalence and degree in subjects submitted to TCCD for conditions theoretically associated or caused by paradoxical embolism to the brain. METHODS: PFO assessment, performed in 10 major diagnostic categories and a control group, followed a standardized protocol with a 10 or 20 microbubbles (MB) cutoff to identify any or only large RLS, respectively. RESULTS: Among 2113 patients, a significant larger RLS prevalence was found in stroke (53.3%), TIA (45.7%) and migraine with aura (39.7%) when compared with non-migraineurs controls (25.5%). RLS degree was significantly higher in stroke and TIA patients: The ROC curve from MB load data helped to identify new cutoff values for both normal breathing (42 MB) and Valsalva (139 MB) tests. From logistic regression, a family history for PFO, ASA, and male gender appeared independent predictors of a RLS. By contrast, RLS seemed independent of white matter abnormalities presence on brain neuroimaging or stroke mimics. CONCLUSIONS: In addition to recently defined criteria, genetically determined inheritable traits and epidemiologic characteristics (male gender) should be taken into account when assessing PFO and related cerebrovascular risk profile. A newly defined threshold in TCCD MB count is suggested to discriminate shunts related to stroke and TIA from innocent ones. PMID- 26139359 TI - Epigenetic mutations can both help and hinder adaptive evolution. AB - Epigenetic variation is being integrated into our understanding of adaptation, yet we lack models on how epigenetic mutations affect evolution that includes de novo genetic change. We model the effects of epigenetic mutations on the dynamics and endpoints of adaptive walks-a process where a series of beneficial mutations move a population towards a fitness optimum. We use an individual-based model of an asexual population, where mutational effects are drawn from Fisher's geometric model. We find cases where epigenetic mutations speed adaptation or result in populations with higher fitness. However, we also find cases where they slow adaptation or result in populations with lower fitness. The effect of epigenetic mutations on adaptive walks depends crucially on their stability and fitness effects relative to genetic mutations, with small-effect epigenetic mutations generally speeding adaptation, and epigenetic mutations with the same fitness effects as genetic mutations slowing adaptation. Our work reveals a complex relationship between epigenetic mutations and natural selection and highlights the need for empirical data. PMID- 26139360 TI - Kinesiology tape does not promote vertical jumping performance: A deceptive crossover trial. AB - BACKGROUND: Kinesiology tape (KINTAPE) is one of the most common adhesive therapeutic tapes. Apart from clinical applications, KINTAPE claims to be able to enhance functional performance by muscle activity facilitation. However, emerging evidence suggests that the isokinetic muscle strength remains similar when the placebo effect is eliminated. OBJECTIVES: In view of the weak relationship between functional performance and isokinetic muscle strength, this study investigated the true effects of KINTAPE on functional performance. DESIGN: Deceptive, randomized, and crossover trial. METHOD: Sixty four experienced volleyball players performed vertical jumping test under three taping conditions: true facilitative KINTAPE, sham KINTAPE, and no KINTAPE. Under the pretense of applying adhesive muscle sensors, KINTAPE was applied to their quadriceps and gastrocnemius in the first two conditions. Mean maximum jump height and peak jump power were averaged from three attempts. Within-subject comparisons were conducted by repeated measure ANOVA. RESULTS: Out of 64 participants, 30 of them were successfully deceived and they were ignorant about KINTAPE. No significant differences were found in both maximum jump height (eta(2) = 0.001; p = 0.241) and peak jump power (eta(2) = 0.001; p = 0.134) between three taping conditions. CONCLUSIONS: The results showed that KINTAPE did not facilitate muscle performance by generating higher jumping power or yielding a better jumping performance. These findings reinforce that previously reported muscle facilitatory effects or functional enhancement using KINTAPE may be attributed to placebo effects. PMID- 26139361 TI - European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation. AB - The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol. PMID- 26139362 TI - Usefulness of traditional echocardiographic parameters in assessment of left ventricular function in patients with normal ejection fraction early after acute myocardial infarction: results from a large consecutive cohort. AB - AIMS: The aim of this study was to assess the frequency of left ventricular (LV) systolic function impairment using classical echocardiographic parameters and their relation to myocardial damage in patients hospitalized for acute myocardial infarction (MI) with normal LV ejection fraction (LVEF >=52% in males or >=54% in females). METHODS AND RESULTS: All 421 consecutive patients with MI included in the REBUS (RElevance of Biomarkers for future risk of thromboembolic events in UnSelected post-myocardial infarction patients) study underwent two-dimensional and Doppler echocardiography within 72 h after admission. A normal LVEF was present in 262 (73.8%) of the 355 patients ultimately enrolled in the study. Patients with normal LVEF more often presented with non-ST-elevation myocardial infarction and had less comorbidities when compared with those with impaired LVEF. No differences in demographic factors or relevant medications were observed. Higher value of mean annular plane systolic excursion (MAPSE), lower wall motion score index (WMSI), lower LV as well as left atrial volumes characterized patients with normal LVEF. Impaired MAPSE was present in 64.4%, WMSI >1 in 72.1%, and dilated left atrium in 33.6% of those patients. Maximal cardiac troponin concentration reflecting infarct size showed the strongest association with WMSI (beta = 0.35), followed by LVEF (beta = -0.29), MAPSE (beta = -0.25), and indexed LV end-systolic volume (beta = 0.19; P < 0.001 for all the models). CONCLUSION: In two-third of patients with MI and normal LVEF, at least one of the other markers of systolic function was outside of the normal range. WMSI reflected the size of MI better than global LV function parameters as LVEF or MAPSE. PMID- 26139363 TI - Memory-Associated Dynamic Regulation of the "Stable" Core of the Chromatin Particle. AB - Chromatin is a critical regulator of neural plasticity, but basic principles of chromatin function in neurons are unclear. In this issue of Neuron, Maze et al. (2015) establish histone H3.3 turnover as a novel mechanism contributing to CNS gene regulation, synaptic plasticity, and cognition. PMID- 26139364 TI - Dissecting the Role of Smooth Muscle Cells versus Pericytes in Regulating Cerebral Blood Flow Using In Vivo Optical Imaging. AB - The brain regulates blood flow to match energy demand to nutrient supply. In this issue of Neuron, using in vivo optical imaging and optogenetics, Hill et al. (2015) report that arteriolar smooth muscle cells are key players in regulating cerebral blood flow in the healthy state and contribute to the "no reflow" phenomenon after ischemic stroke. PMID- 26139365 TI - Behavioral State--Getting "In The Zone". AB - In this issue of Neuron, McGinley et al. (2015) investigate a classic observation from psychology linking arousal state with behavioral performance, demonstrating neural correlates of an "optimal" state for an auditory detection task. PMID- 26139366 TI - The Hippocampus as a Cognitive Map ... of Social Space. AB - The traditional view of the hippocampus is that it creates a cognitive map to navigate physical space. Here, in this issue of Neuron, Tavares et al. (2015) show that the human hippocampus maps dimensions of social space, indicating a function in the service of navigating everyday life. PMID- 26139367 TI - Alternative Splicing in the Mammalian Nervous System: Recent Insights into Mechanisms and Functional Roles. AB - High-throughput transcriptomic profiling approaches have revealed that alternative splicing (AS) of precursor mRNAs, a fundamental process by which cells expand their transcriptomic diversity, is particularly widespread in the nervous system. AS events detected in the brain are more highly conserved than those detected in other tissues, suggesting that they more often provide conserved functions. Our understanding of the mechanisms and functions of neural AS events has significantly advanced with the coupling of various computational and experimental approaches. These studies indicate that dynamic regulation of AS in the nervous system is critical for modulating protein-protein interactions, transcription networks, and multiple aspects of neuronal development. Furthermore, several underappreciated classes of AS with the aforementioned roles in neuronal cells have emerged from unbiased, global approaches. Collectively, these findings emphasize the importance of characterizing neural AS in order to gain new insight into pathways that may be altered in neurological diseases and disorders. PMID- 26139369 TI - Dealing with Danger in the CNS: The Response of the Immune System to Injury. AB - Fighting pathogens and maintaining tissue homeostasis are prerequisites for survival. Both of these functions are upheld by the immune system, though the latter is often overlooked in the context of the CNS. The mere presence of immune cells in the CNS was long considered a hallmark of pathology, but this view has been recently challenged by studies demonstrating that immunological signaling can confer pivotal neuroprotective effects on the injured CNS. In this review, we describe the temporal sequence of immunological events that follow CNS injury. Beginning with immediate changes at the injury site, including death of neural cells and release of damage-associated molecular patterns (DAMPs), and progressing through innate and adaptive immune responses, we describe the cascade of inflammatory mediators and the implications of their post-injury effects. We conclude by proposing a revised interpretation of immune privilege in the brain, which takes beneficial neuro-immune communications into account. PMID- 26139368 TI - RNA Structures as Mediators of Neurological Diseases and as Drug Targets. AB - RNAs adopt diverse folded structures that are essential for function and thus play critical roles in cellular biology. A striking example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that orchestrates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have revealed other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures contribute to disease. In this Review, we provide a brief introduction into RNA structural biology and then describe how RNA structures function in cells and cause or contribute to neurological disease. Finally, we highlight successful applications of rational design principles to provide chemical probes and lead compounds targeting structured RNAs. Based on several examples of well-characterized RNA-driven neurological disorders, we demonstrate how designed small molecules can facilitate the study of RNA dysfunction, elucidating previously unknown roles for RNA in disease, and provide lead therapeutics. PMID- 26139370 TI - Biochemical Computation for Spine Structural Plasticity. AB - The structural plasticity of dendritic spines is considered to be essential for various forms of synaptic plasticity, learning, and memory. The process is mediated by a complex signaling network consisting of numerous species of molecules. Furthermore, the spatiotemporal dynamics of the biochemical signaling are regulated in a complicated manner because of geometrical restrictions from the unique morphology of the dendritic branches and spines. Recent advances in optical techniques have enabled the exploration of the spatiotemporal aspects of the signal regulations in spines and dendrites and have provided many insights into the principle of the biochemical computation that underlies spine structural plasticity. PMID- 26139371 TI - Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. AB - Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation-associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity, and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near-saturating levels throughout the neuronal genome by mid adolescence. Despite such accumulation, H3.3-containing nucleosomes remain highly dynamic-in a modification-independent manner-to control neuronal- and glial specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical and previously undocumented regulator of cell type-specific transcription and plasticity in mammalian brain. PMID- 26139372 TI - Oxytocin Mediates Entrainment of Sensory Stimuli to Social Cues of Opposing Valence. AB - Meaningful social interactions modify behavioral responses to sensory stimuli. The neural mechanisms underlying the entrainment of neutral sensory stimuli to salient social cues to produce social learning remain unknown. We used odor driven behavioral paradigms to ask if oxytocin, a neuropeptide implicated in various social behaviors, plays a crucial role in the formation of learned associations between odor and socially significant cues. Through genetic, optogenetic, and pharmacological manipulations, we show that oxytocin receptor signaling is crucial for entrainment of odor to social cues but is dispensable for entrainment to nonsocial cues. Furthermore, we demonstrate that oxytocin directly impacts the piriform, the olfactory sensory cortex, to mediate social learning. Lastly, we provide evidence that oxytocin plays a role in both appetitive and aversive social learning. These results suggest that oxytocin conveys saliency of social stimuli to sensory representations in the piriform cortex during odor-driven social learning. PMID- 26139373 TI - An Interglomerular Circuit Gates Glomerular Output and Implements Gain Control in the Mouse Olfactory Bulb. AB - Odors elicit distributed activation of glomeruli in the olfactory bulb (OB). Crosstalk between co-active glomeruli has been proposed to perform a variety of computations, facilitating efficient extraction of sensory information by the cortex. Dopaminergic/GABAergic cells in the OB, which can be identified by their expression of the dopamine transporter (DAT), provide the earliest opportunity for such crosstalk. Here we show in mice that DAT+ cells carry concentration dependent odor signals and broadcast focal glomerular inputs throughout the OB to cause suppression of mitral/tufted (M/T) cell firing, an effect that is mediated by the external tufted (ET) cells coupled to DAT+ cells via chemical and electrical synapses. We find that DAT+ cells implement gain control and decorrelate odor representations in the M/T cell population. Our results further indicate that ET cells are gatekeepers of glomerular output and prime determinants of M/T responsiveness. PMID- 26139374 TI - A Modality-Specific Feedforward Component of Choice-Related Activity in MT. AB - The activity of individual sensory neurons can be predictive of an animal's choices. These decision signals arise from network properties dependent on feedforward and feedback inputs; however, the relative contributions of these inputs are poorly understood. We determined the role of feedforward pathways to decision signals in MT by recording neuronal activity while monkeys performed motion and depth tasks. During each session, we reversibly inactivated V2 and V3, which provide feedforward input to MT that conveys more information about depth than motion. We thus monitored the choice-related activity of the same neuron both before and during V2/V3 inactivation. During inactivation, MT neurons became less predictive of decisions for the depth task but not the motion task, indicating that a feedforward pathway that gives rise to tuning preferences also contributes to decision signals. We show that our data are consistent with V2/V3 input conferring structured noise correlations onto the MT population. PMID- 26139375 TI - Rapid Encoding of New Memories by Individual Neurons in the Human Brain. AB - The creation of memories about real-life episodes requires rapid neuronal changes that may appear after a single occurrence of an event. How is such demand met by neurons in the medial temporal lobe (MTL), which plays a fundamental role in episodic memory formation? We recorded the activity of MTL neurons in neurosurgical patients while they learned new associations. Pairs of unrelated pictures, one of a person and another of a place, were used to construct a meaningful association modeling the episodic memory of meeting a person in a particular place. We found that a large proportion of responsive MTL neurons expanded their selectivity to encode these specific associations within a few trials: cells initially responsive to one picture started firing to the associated one but not to others. Our results provide a plausible neural substrate for the inception of associations, which are crucial for the formation of episodic memories. PMID- 26139376 TI - A Map for Social Navigation in the Human Brain. AB - Deciphering the neural mechanisms of social behavior has propelled the growth of social neuroscience. The exact computations of the social brain, however, remain elusive. Here we investigated how the human brain tracks ongoing changes in social relationships using functional neuroimaging. Participants were lead characters in a role-playing game in which they were to find a new home and a job through interactions with virtual cartoon characters. We found that a two dimensional geometric model of social relationships, a "social space" framed by power and affiliation, predicted hippocampal activity. Moreover, participants who reported better social skills showed stronger covariance between hippocampal activity and "movement" through "social space." The results suggest that the hippocampus is crucial for social cognition, and imply that beyond framing physical locations, the hippocampus computes a more general, inclusive, abstract, and multidimensional cognitive map consistent with its role in episodic memory. PMID- 26139377 TI - Causes of mortality due to rheumatic diseases in Jerez de los Caballeros (Badajoz) during the 19th century. AB - A total of 26,203 of the deaths in Jerez de los Caballeros (Badajoz) during the 19th century were collected and grouped according to the Bertillon's Classification, in order to study the causes of death from rheumatic diseases. An analysis was made using the Death Registers, those located in the Parish Archives, and files of the Municipal Archives. There were a total of 31 deaths due to rheumatic diseases, with the 65-74 years age group being most frequent. The lack of records may be due to the inaccuracy of the diagnoses. September was the month of increased mortality. PMID- 26139378 TI - Allergic contact dermatitis in medical professionals due to exposure to ultrasound gel. PMID- 26139379 TI - Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants. AB - PURPOSE: Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling approach. METHODS: A population pharmacokinetic model was developed in NONMEM VI, based on paracetamol plasma concentrations from 54 preterm and term neonates and infants, and on paracetamol, paracetamol-glucuronide and paracetamol-sulphate amounts in urine from 22 of these patients. Patients received either a single intravenous propacetamol dose or up to 12 repeated doses. RESULTS: Paracetamol and metabolite disposition was best described with one-compartment models. The formation clearance of paracetamol-sulphate was 1.46 mL/min/kg(1.4), which was about 5.5 times higher than the formation clearance of the glucuronide of 0.266 mL/min/kg. The renal excretion rate constants of both metabolites was estimated to be 11.4 times higher than the excretion rate constant of unchanged paracetamol, yielding values of 0.580 mL/min/kg. Developmental changes were best described by bodyweight in linear relationships on the distribution volumes, the formation of paracetamol glucuronide and the unchanged excretion of paracetamol, and in an exponential relationship on the formation of paracetamol-sulphate. There was no evidence for up-regulation or other time-varying changes in any of the model parameters. Simulations with this model illustrate how paracetamol-glucuronide recovery in urine increases over time due to the slower formation of this metabolite and in the absence of up-regulation. CONCLUSIONS: Developmental changes, described by bodyweight-based functions, rather than up-regulation, explain developmental changes in paracetamol disposition in neonates and infants. PMID- 26139380 TI - BoLA-6*01301 and BoLA-6*01302, two allelic variants of the A18 haplotype, present the same epitope from the Tp1 antigen of Theileria parva. AB - We have recently shown that the BoLA-A18 variant haplotype (BoLA-6*01302) is more prevalent than the BoLA-A18 haplotype (BoLA-6*01301) in a sample of Holstein/Friesian cattle in Kenya. These MHC class I allelic variants differ by a single amino acid polymorphism (Glu97 to Leu97) in the peptide-binding groove. We have previously mapped an 11-mer peptide epitope from the Theileria parva antigen Tp1 (Tp1214-224) that is presented by BoLA-6*01301. Crystal structure data indicates that Glu97 in the MHC molecule plays a role in epitope binding through electro-static interaction with a lysine residue in position 5 of the epitope, which also functions as an additional anchor residue. In contrast to expectations, we demonstrate that the amino acid substitution in BoLA-6*01302 does not divert the CTL response away from Tp1214-224. The two MHC molecules exhibit similar affinity for the Tp1 epitope and can present the epitope to parasite-specific CTLs derived from either BoLA allelic variants. These data confirm that this BoLA polymorphism does not alter Tp1 epitope specificity and that both allelic variants can be used for Tp1 vaccine studies. PMID- 26139382 TI - Emodin Attenuates Cigarette Smoke Induced Lung Injury in a Mouse Model via Suppression of Reactive Oxygen Species Production. AB - Emodin has antioxidative activities. Here, we investigated the effects of emodin on cigarette smoke (CS)-induced acute lung inflammation. Mice (C57BL/6) were exposed to CS. Emodin was administrated with intraperitoneal bolus injection of emodin (20 or 40 mg/kg) daily 1 h before CS exposure. Emodin inhibited CS-induced inflammatory cells infiltration in mouse lungs, especially at 40 mg/kg. Moreover, emodin resulted in significant reductions in total bronchoalveolar lavage fluid (BALF) cells, as compared with air exposure control, coupled with decreases in BALF cytokines. The activities of superoxide dismutase, catalase, and glutathione peroxidase were remarkably enhanced by emodin in CS-exposed mice. Emodin enhanced CS-induced expression of heme oxygenase-1 and nuclear factor-erythroid 2-related factor-2 (both are antioxidative genes) at both mRNA and protein levels, and profoundly promoted their activities in CS-treated mice. Collectively, our results suggested that emodin protects mouse lung from CS-induced lung inflammation and oxidative damage, most likely through its antioxidant activity. PMID- 26139381 TI - Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics--Fluoroquinolones. AB - Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics. PMID- 26139383 TI - Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures. AB - The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1 mg K/L to 3 mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined. PMID- 26139385 TI - Relationship between Neutrophil-to-Lymphocyte Ratio and Left Ventricular Free Wall Rupture in Acute Myocardial Infarction. AB - OBJECTIVES: This study aimed to evaluate the relationship between the neutrophil to-lymphocyte (N/L) ratio and left ventricular free wall rupture (LVFWR) in patients with ST elevation myocardial infarction (STEMI). Previous studies showed a correlation between increased levels of inflammatory markers and adverse cardiovascular events. The role of inflammation markers, particularly the N/L ratio, in mechanical complications after myocardial infarction has not been studied. METHODS: Retrospectively, we compared the N/L ratio values of 23 patients with STEMI complicated by LVFWR with 214 STEMI patients without this complication. The diagnosis of rupture was confirmed by echocardiography in each case. RESULTS: Neutrophil counts [median 8.5 * 103/ul, interquartile range (IQR) 6.4, vs. 7.8 * 103/ul, IQR 4.7, p = 0.02] and the N/L ratio (5.66, IQR 4.17, vs. 4.1, IQR 3.93, p = 0.01) were significantly higher in the LVFWR group. In receiver operating characteristic analysis, an N/L ratio above 3.7 predicted LVFWR with a sensitivity of 82.6% and a specificity of 46.9% (area under the curve = 0.654, p = 0.016). In multivariate regression analysis, age, hypertension, increased creatinine levels and increased N/L ratio (odds ratio = 1.61, 95% confidence interval = 1.15-2.23, p = 0.01) were found to be independent predictors of LVFWR. CONCLUSIONS: In our study, the N/L ratio was found to be independently correlated with the risk of LVFWR. (c) 2015 S. Karger AG, Basel. PMID- 26139384 TI - Cardiovascular magnetic resonance feature-tracking assessment of myocardial mechanics: Intervendor agreement and considerations regarding reproducibility. AB - AIM: To assess intervendor agreement of cardiovascular magnetic resonance feature tracking (CMR-FT) and to study the impact of repeated measures on reproducibility. MATERIALS AND METHODS: Ten healthy volunteers underwent cine imaging in short-axis orientation at rest and with dobutamine stimulation (10 and 20 MUg/kg/min). All images were analysed three times using two types of software (TomTec, Unterschleissheim, Germany and Circle, cvi(42), Calgary, Canada) to assess global left ventricular circumferential (Ecc) and radial (Err) strains and torsion. Differences in intra- and interobserver variability within and between software types were assessed based on single and averaged measurements (two and three repetitions with subsequent averaging of results, respectively) as determined by Bland-Altman analysis, intraclass correlation coefficients (ICC), and coefficient of variation (CoV). RESULTS: Myocardial strains and torsion significantly increased on dobutamine stimulation with both types of software (p<0.05). Resting Ecc and torsion as well as Ecc values during dobutamine stimulation were lower measured with Circle (p<0.05). Intra- and interobserver variability between software types was lowest for Ecc (ICC 0.81 [0.63-0.91], 0.87 [0.72-0.94] and CoV 12.47% and 14.3%, respectively) irrespective of the number of analysis repetitions. Err and torsion showed higher variability that markedly improved for torsion with repeated analyses and to a lesser extent for Err. On an intravendor level TomTec showed better reproducibility for Ecc and torsion and Circle for Err. CONCLUSIONS: CMR-FT strain and torsion measurements are subject to considerable intervendor variability, which can be reduced using three analysis repetitions. For both vendors, Ecc qualifies as the most robust parameter with the best agreement, albeit lower Ecc values obtained using Circle, and warrants further investigation of incremental clinical merit. PMID- 26139386 TI - Detection of the long noncoding RNAs nuclear-enriched autosomal transcript 1 (NEAT1) and metastasis associated lung adenocarcinoma transcript 1 in the peripheral blood of HIV-1-infected patients. AB - OBJECTIVES: Long noncoding RNAs (lncRNAs) in HIV-1 infection have not been extensively studied. Here we detected two lncRNAs, nuclear-enriched autosomal transcript 1 (NEAT1) and metastasis associated lung adenocarcinoma transcript 1 (MALAT1), in peripheral blood mononuclear cells (PBMCs) and plasma of HIV-1 infected patients. METHODS: Fifty-nine HIV-1-infected patients and 21 healthy controls were recruited for the study, of whom 31 patients were highly active antiretroviral therapy (HAART)-naive and 28 patients had been receiving HAART for more than 1 year with undetectable viral loads. Total RNA was extracted from PBMCs and plasma, and levels of NEAT1 and MALAT1 were determined by quantitative real-time polymerase chain reaction. RESULTS: We found that the levels of NEAT1 and MALAT1 in PBMCs were up-regulated in HAART-naive patients and were reduced in patients receiving HAART. NEAT1 was down-regulated in the plasma of infected patients and expression was correlated with CD4 T-cell count. CONCLUSIONS: Our findings suggest that NEAT1 and MALAT1 may interact with HIV-1 in vivo and that the presence of NEAT1 in plasma is a potential biomarker of HIV-1 infection. PMID- 26139387 TI - Costs of some drugs will be displayed on packs to try to reduce waste and improve adherence. PMID- 26139388 TI - Improving Pediatric Basic Life Support Performance Through Blended Learning With Web-Based Virtual Patients: Randomized Controlled Trial. AB - BACKGROUND: E-learning and blended learning approaches gain more and more popularity in emergency medicine curricula. So far, little data is available on the impact of such approaches on procedural learning and skill acquisition and their comparison with traditional approaches. OBJECTIVE: This study investigated the impact of a blended learning approach, including Web-based virtual patients (VPs) and standard pediatric basic life support (PBLS) training, on procedural knowledge, objective performance, and self-assessment. METHODS: A total of 57 medical students were randomly assigned to an intervention group (n=30) and a control group (n=27). Both groups received paper handouts in preparation of simulation-based PBLS training. The intervention group additionally completed two Web-based VPs with embedded video clips. Measurements were taken at randomization (t0), after the preparation period (t1), and after hands-on training (t2). Clinical decision-making skills and procedural knowledge were assessed at t0 and t1. PBLS performance was scored regarding adherence to the correct algorithm, conformance to temporal demands, and the quality of procedural steps at t1 and t2. Participants' self-assessments were recorded in all three measurements. RESULTS: Procedural knowledge of the intervention group was significantly superior to that of the control group at t1. At t2, the intervention group showed significantly better adherence to the algorithm and temporal demands, and better procedural quality of PBLS in objective measures than did the control group. These aspects differed between the groups even at t1 (after VPs, prior to practical training). Self-assessments differed significantly only at t1 in favor of the intervention group. CONCLUSIONS: Training with VPs combined with hands-on training improves PBLS performance as judged by objective measures. PMID- 26139389 TI - Risk matrix model for prediction of colectomy in a population-based study of ulcerative colitis patients (the IBSEN study). AB - OBJECTIVES: Identifying ulcerative colitis (UC) patients with increased risk of colectomy is essential for appropriate treatment. We aimed to develop a prediction model assessing the risk of having colectomy within the first 10 years after diagnosis. MATERIAL AND METHODS: A population-based inception cohort of UC patients diagnosed in south-eastern Norway between 1990 and 1994 has been followed for 10 years. Altogether 519 patients were recruited including 49 patients who were colectomized. Based on the best-fitted multivariate model, the probabilities of colectomy were computed for selected levels of baseline covariates, and the results arranged in a prediction matrix. The following risk factors at diagnosis were analyzed: age, smoking, sex, disease extent, weight loss and fever and need for systemic steroids. Biochemical markers included C reactive protein (CRP, <30 or >=30 mg/l); erythrocyte sedimentation rate (ESR, <30 or >=30 mm/h) and hemoglobin (Hgb, <10.5 or >= 10.5 g/dL). RESULTS: Extent of disease, age (<40 years, >=40 years), need for systemic steroids and CRP or ESR (<30 or >=30) at diagnosis were independently associated with colectomy and were combined in a prediction matrix. The probabilities of colectomy during the follow up period ranged from 2.6% to 40.1% depending on the combination of predictors at diagnosis. CONCLUSIONS: Our prediction model revealed significant differences in the probability of undergoing colectomy during a 10-years course of disease, which supports an early individualized treatment approach in UC. PMID- 26139390 TI - Enzymatic synthesis and post-functionalization of two-dimensional crystalline cellulose oligomers with surface-reactive groups. AB - Two-dimensional (2D) nanomaterials have gained considerable attention due to their unique structural and physicochemical properties. Herein, we synthesized 2D crystalline cellulose oligomers with surface-reactive azide groups through enzymatic reactions and covalently post-functionalized them with 1-ethynyl pyrene through copper(i)-catalyzed Huisgen cycloaddition reactions. PMID- 26139391 TI - Electron Backscatter Diffraction and Transmission Kikuchi Diffraction Analysis of an Austenitic Stainless Steel Subjected to Surface Mechanical Attrition Treatment and Plasma Nitriding. AB - Austenitic 316L stainless steel can be used for orthopedic implants due to its biocompatibility and high corrosion resistance. Its range of applications in this field could be broadened by improving its wear and friction properties. Surface properties can be modified through surface hardening treatments. The effects of such treatments on the microstructure of the alloy were investigated here. Surface Mechanical Attrition Treatment (SMAT) is a surface treatment that enhances mechanical properties of the material surface by creating a thin nanocrystalline layer. After SMAT, some specimens underwent a plasma nitriding process to further enhance their surface properties. Using electron backscatter diffraction, transmission Kikuchi diffraction, energy dispersive spectroscopy, and transmission electron microscopy, the microstructural evolution of the stainless steel after these different surface treatments was characterized. Microstructural features investigated include thickness of the nanocrystalline layer, size of the grains within the nanocrystalline layer, and depth of diffusion of nitrogen atoms within the material. PMID- 26139392 TI - Gene-asbestos interaction in malignant pleural mesothelioma susceptibility. AB - Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor. PMID- 26139394 TI - Health risk assessment of metals in food crops and related soils amended with biogas slurry in Taihu Basin: perspective from field experiment. AB - A health risk assessment of food crops contaminated with heavy metals (Cu, Zn, Pb, As, Cd, and Cr) through the intake of cereals and vegetables grown from biogas slurry irrigated sites was conducted. In the vegetable soils and cereal soils, the concentrations of Zn, Pb, and Cd were far higher than Chinese agricultural standards. The pollution conditions of the aforementioned heavy metals varied with the seasons. Typically, the pollution was more serious in summer than in autumn. Furthermore, the accumulative properties of the heavy metals were different in the cereals and vegetables. In particular, Cu, Zn, and Pb tended to accumulate in rice with concentrations of 6.70, 36.58, and 4.14 mg kg(-1), respectively. Pb and Cd in cereals and vegetables exceeded the maximum permissible concentrations in China. The health risk assessment revealed that the daily intake (DI) and target hazard quotients (THQs) of Pb, As, and Cd in cereals and vegetables also exceeded the FAO/WHO limit. The results indicated that heavy metal contamination posed a severe health risk to local humans. PMID- 26139395 TI - Restoration of rare earth mine areas: organic amendments and phytoremediation. AB - Overexploitation of rare earth mine has caused serious desertification and various environmental issues, and ecological restoration of a mining area is an important concern in China. In this study, experiments involving dry grass landfilling, chicken manure broadcasting, and plant cultivation were carried out to reclaim a rare earth mine area located in Heping County, Guangdong Province, China. The prime focus was to improve soil quality in terms of nutrients, microbial community, enzyme activity, and physicochemical properties so as to reclaim the land. After 2 years of restoration, an increase of organic matter (OM), available potassium (K), available phosphorus (P) levels, and acid phosphatase (ACP) activity and a reduction of the available nitrogen (N) level and urease (URE) activity in soil were achieved compared to the original mined land. The nutrients and enzyme activities in soil with 5 years of restoration were close to or surpass those in the unexploited land as control. The bulk density, total porosity, water holding capacity, pH, and electrical conductivity (EC) of soil were improved, and the number of cultivable microorganisms and the bacterial diversity in soil were greatly increased with time during ecological restoration, especially for surface soil. Furthermore, the artificial vegetation stably grew at the restored mining sites. The results indicated that organic amendments and phytoremediation could ecologically restore the rare earth mining sites and the mined land could finally be planted as farmland. PMID- 26139396 TI - Prediction and assessment of ecogenotoxicity of antineoplastic drugs in binary mixtures. AB - The combined genotoxic effects of four anticancer drugs (5-fluorouracil [5-FU], cisplatin [CDDP], etoposide [ET], and imatinib mesylate [IM]) were studied testing their binary mixtures in two crustaceans that are part of the freshwater food chain, namely Daphnia magna and Ceriodaphnia dubia. Genotoxicity was assessed using the in vivo comet assay. Assessment was based on two distinct effect sizes determined from dose-response experiments. Doses for single and combined exposures expected to result in these effect sizes were computed based on Bliss independence as reference model. Statistical comparison by analysis of variance of single and combined toxicities allowed accepting or rejecting the independency hypothesis. The results obtained for D. magna showed independent action for all mixtures except for IM+5-FU that showed an antagonistic interaction. In C. dubia, most mixtures had antagonist interactions except IM+5 FU and IM+CDDP that showed Bliss independence. Despite the antagonistic interactions, our results demonstrated that combinations of anticancer drugs could be of environmental concern because effects occur at very low concentrations that are in the range of concentrations encountered in aquatic systems. PMID- 26139397 TI - The accumulation and potential ecological risk of heavy metals in microalgae from a eutrophic lake (Taihu Lake, China). AB - This study aimed to evaluate the bioaccumulation and enrichment of heavy metals in dominant microalgae and assess the potential ecological risk to the microalgae located at the northern region of Taihu Lake, China, a shallow freshwater lake. The concentrations of heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in water and microalgae (predominant cyanophyta) collected from the north of Taihu Lake were analyzed. Subsequently, enrichment factors (EF) for heavy metals in microalgae relative to water were calculated. The concentrations and EF values of heavy metals were significantly higher in water and microalgae from the northern region compared with other regions for all the metals except As and Hg. Among the metals, Pb and Cd possessed higher enrichment levels, approx. 200 and 400 for Pb and Cd, respectively. This suggested that Pb and Cd had stronger chemisorption on microalgae, even though present at lower concentrations. Moreover, Ni and Zn in microalgae from the north of the lake also exhibited risk to the ecosystem owing to their high concentrations. In general, the microalgae tended to enrich Pb, Cd, Ni, and Zn by biosorption and bioaccumulation and thus exert a risk to the ecosystem and human populations. PMID- 26139398 TI - PAH occurrence in chalk river systems from the Jura region (France). Pertinence of suspended particulate matter and sediment as matrices for river quality monitoring. AB - This study investigates the variations of polycyclic aromatic hydrocarbon (PAH) levels in surface water, suspended particulate matter (SPM) and sediment upstream and downstream of the discharges of two wastewater treatment plant (WWTP) effluents. Relationships between the levels of PAHs in these different matrices were also investigated. The sum of 16 US EPA PAHs ranged from 73.5 to 728.0 ng L( 1) in surface water and from 85.4 to 313.1 ng L(-1) in effluent. In SPM and sediment, ?16PAHs ranged from 749.6 to 2,463 MUg kg(-1) and from 690.7 MUg kg(-1) to 3,625.6 MUg kg(-1), respectively. Investigations performed upstream and downstream of both studied WWTPs showed that WWTP discharges may contribute to the overall PAH contaminations in the Loue and the Doubs rivers. Comparison between gammarid populations upstream and downstream of WWTP discharge showed that biota was impacted by the WWTP effluents. When based only on surface water samples, the assessment of freshwater quality did not provide evidence for a marked PAH contamination in either of the rivers studied. However, using SPM and sediment samples, we found PAH contents exceeding sediment quality guidelines. We conclude that sediment and SPM are relevant matrices to assess overall PAH contamination in aquatic ecosystems. Furthermore, we found a positive linear correlation between PAH contents of SPM and sediment, showing that SPM represents an integrating matrix which is able to provide meaningful data about the overall contamination over a given time span. PMID- 26139399 TI - Dissipation kinetics and degradation mechanism of amicarbazone in soil revealed by a reliable LC-MS/MS method. AB - A sensitive and reliable analytical method was developed for simultaneous determination of amicarbazone (AMZ) and its two major metabolites including desamino amicarbazone (DA) and isopropyl-2-hydroxy-DA-amicarbazone (Ipr-2-OH-DA AMZ) in soil for the first time. Targeted analytes were extracted and purified using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure, and then analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a total run time of 9 min. The established approach was extensively validated by determining the linearity (R (2) >= 0.99), recovery (84 96 ), sensitivity (limits of quantification at 5-10 MUg kg(-1)), and precision (RSDs <=12 %). Based on the methodological advances, the subsequent dissipation kinetics and degradation mechanism of amicarbazone in soil were thoroughly investigated in an illumination incubator. As revealed, AMZ was easily degraded with the half-lives of 13.9-19.7 days in soil. Field trial results of AMZ (40 g a.i. ha(-1)) in Shanghai showed that the residues of AMZ and its metabolite Ipr-2 OH-DA-AMZ decreased from 0.505 mg kg(-1) (day 50) to 0.038 mg kg(-1) (day 365) and from 0.099 mg kg(-1) (day 50) to 0.028 mg kg(-1) (day 365), respectively, while the content of DA increased from 0.097 mg kg(-1) (day 50) to 0.245 mg kg( 1) (day 365). This study provided valuable data to understand the toxicity of AMZ and substantially promote its safe application to protect environment and human health. PMID- 26139400 TI - Occurrence of pharmaceuticals in municipal wastewater, in the recipient water, and sedimented particles of northern Lake Paijanne. AB - The presence of five different pharmaceuticals, consisting of four anti inflammatory and one antiepileptic drug, was determined in influent and effluent of a municipal wastewater treatment plant (WWTP) near the city of Jyvaskyla, Finland, and in the receiving water, northern Lake Paijanne. In addition, samples of sedimented particles were collected among water samples from five locations near the discharge point of the treated wastewater. The solid phase extracts (SPEs) of water samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The studied pharmaceuticals were detected from influent, effluent, and lake water but also in the sedimented particles. The concentrations of carbamazepine, diclofenac, ibuprofen, ketoprofen, and naproxen in Lake Paijanne ranged from 1 to 21 ng L(-1), 4 to 209 ng L(-1), 5 to 836 ng L(-1), 9 to 952 ng L(-1), and 2 to 129 ng L(-1), respectively. The concentrations of ketoprofen in sedimented particles ranged from 79 to 135 MUg g(-1) while only trace amounts of other selected pharmaceuticals were detected. The results indicate that the concentrations of pharmaceuticals are affected by the biological and chemical reactions occurring in the wastewater treatment processes but also by the UV light in the photic layer of Lake Paijanne. It can be concluded that considerable amount of selected pharmaceuticals are present in the influent and effluent of municipal WWTP but also in the water phase and sedimented particles of northern Lake Paijanne. PMID- 26139401 TI - Impact of sludge stabilization processes and sludge origin (urban or hospital) on the mobility of pharmaceutical compounds following sludge landspreading in laboratory soil-column experiments. AB - This study aimed to determine the effect of sludge stabilization treatments (liming and anaerobic digestion) on the mobility of different pharmaceutical compounds in soil amended by landspreading of treated sludge from different sources (urban and hospital). The sorption and desorption potential of the following pharmaceutical compounds: carbamazepine (CBZ), ciprofloxacin (CIP), sulfamethoxazole (SMX), salicylic acid (SAL), ibuprofen (IBU), paracetamol (PAR), diclofenac (DIC), ketoprofen (KTP), econazole (ECZ), atenolol (ATN), and their solid-liquid distribution during sludge treatment (from thickening to stabilization) were investigated in the course of batch testing. The different sludge samples were then landspread at laboratory scale and leached with an artificial rain simulating 1 year of precipitation adapted to the surface area of the soil column used. The quality of the resulting leachate was investigated. Results showed that ibuprofen had the highest desorption potential for limed and digested urban and hospital sludge. Ibuprofen, salicylic acid, diclofenac, and paracetamol were the only compounds found in amended soil leachates. Moreover, the leaching potential of these compounds and therefore the risk of groundwater contamination depend mainly on the origin of the sludge because ibuprofen and diclofenac were present in the leachates of soils amended with urban sludge, whereas paracetamol and salicylic acid were found only in the leachates of soils amended with hospital sludge. Although carbamazepine, ciprofloxacin, sulfamethoxazole, ketoprofen, econazole, and atenolol were detected in some sludge, they were not present in any leachate. This reflects either an accumulation and/or (bio)degradation of these compounds (CBZ, CIP, SMX, KTP, ECZ, and ATN ), thus resulting in very low mobility in soil. Ecotoxicological risk assessment, evaluated by calculating the risk quotients for each studied pharmaceutical compound, revealed no high risk due to the application on the soil of sludge stabilized by liming or anaerobic digestion. PMID- 26139402 TI - Effects of atrazine on photosynthesis and defense response and the underlying mechanisms in Phaeodactylum tricornutum. AB - Atrazine (ATZ) is a commonly used herbicide that has recently come under scrutiny due to potential environmental toxicity and contamination. In this study, we found that the administration of ATZ indeed leads to reduction of photosynthesis and oxidative stress in Phaeodactylum tricornutum at the treated doses higher than 100 MUg L(-1) after 48 h. We further explored the effect of ATZ on photosystem II (PSII) and gene expression of electron transport chain. Collectively, our results may suggest that ATZ entered the chloroplasts in alga depending on ATZ's liposolubility and directly attacked on the electron transport chain, especially PSII, contributing to reactive oxygen species (ROS) burst. The increasing ROS could act as signals to induce or disturb the expression of photosynthesis-related genes, resulting in the imbalance of antioxidation and pro oxidation in the alga. PMID- 26139404 TI - Removal of PCBs and HCB from contaminated solids using a novel successive self propagated sintering process. AB - Thermal treatments are the primary technologies used to remove persistent organic pollutants from contaminated solids. The high energy consumption during continuous heating, required cost for treating the exhaust gas, and potential formation of secondary pollutants during combustion have prevented their implementation. A novel successive self-propagated sintering process was proposed for removing polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) from contaminated solids in a low-cost and environmentally friendly way. Nine laboratory-scale experiments involving different initial concentrations of pollutants and solid compositions were performed. Almost all PCBs (>99%) and HCB (>97%) were removed from solids under constant experimental conditions. Varying initial concentrations of PCBs and HCB in the contaminated solids did not influence the removal efficiency of the pollutants; however, the degradation efficiency of pollutants increased as their initial concentrations increased. Although varying levels of PCDD/Fs were detected in the effluent gas, they were all within the emission standard limit. PMID- 26139403 TI - Plant-bacteria partnerships for the remediation of persistent organic pollutants. AB - High toxicity, bioaccumulation factor and widespread dispersal of persistent organic pollutants (POPs) cause environmental and human health hazards. The combined use of plants and bacteria is a promising approach for the remediation of soil and water contaminated with POPs. Plants provide residency and nutrients to their associated rhizosphere and endophytic bacteria. In return, the bacteria support plant growth by the degradation and detoxification of POPs. Moreover, they improve plant growth and health due to their innate plant growth-promoting mechanisms. This review provides a critical view of factors that affect absorption and translocation of POPs in plants and the limitations that plant have to deal with during the remediation of POPs. Moreover, the synergistic effects of plant-bacteria interactions in the phytoremediation of organic pollutants with special reference to POPs are discussed. PMID- 26139405 TI - Alleviating the toxicity of heavy metals by combined amendments in cultivated bag of Pleurotus cornucopiae. AB - The substrate of mushroom can be polluted with heavy metals and subsequently contaminate mushroom, which requires alternative solutions to reduce associated environmental and human health risks. The effects of amendment application on alleviating Cu and Cd toxicities to Pleurotus cornucopiae were investigated in a cultivated bag experiment conducted with the naturally contaminated substrate. Addition of combined amendments (sodium bentonite, silicon fertilizer, activated carbon, and potassium dihydrogen phosphate) increased the P. cornucopiae biomass and substrate pH. Cu and Cd concentration in P. cornucopiae as well as the available Cu and Cd in substrate reduced for the presence of amendments, and the silicon fertilizer had the biggest inhibition on metal uptake. The smallest amount of Cu and Cd in P. cornucopiae was only 30.8 and 5.51% of control, respectively. Moreover, application of amendments also decreased malondialdehyde (MDA) and hydrogen peroxide (H2O2) level in metal-stressed mushroom by 4.38-53.74 and 8.90-58.42% relative to control, respectively. The decreased oxidative stress could well contribute to the growth of P. cornucopiae, and the elevated substrate pH might lead to the lower metal availability, thus resulting in the reduction of metal accumulation in mushroom. These above results suggest that application of combined amendments in mushroom substrate could be implemented in a general scheme aiming at controlling metal content in P. cornucopiae. PMID- 26139406 TI - Synthesis, characterization, and application of 1-butyl-3-methylimidazolium thiocyanate for extractive desulfurization of liquid fuel. AB - 1-Butyl-3-methylimidazolium thiocyanate [BMIM]SCN has been presented on extractive desulfurization of liquid fuel. The FTIR, (1)H-NMR, and C-NMR have been discussed for the molecular confirmation of synthesized [BMIM]SCN. Further, thermal, conductivity, moisture content, viscosity, and solubility analyses of [BMIM]SCN were carried out. The effects of time, temperature, sulfur compounds, ultrasonication, and recycling of [BMIM]SCN on removal of dibenzothiophene from liquid fuel were also investigated. In extractive desulfurization, removal of dibenzothiophene in n-dodecane was 86.5 % for mass ratio of 1:1 in 30 min at 30 degrees C under the mild process conditions. [BMIM]SCN could be reused five times without a significant decrease in activity. Also, in the desulfurization of real fuels, multistage extraction was examined. The data and results provided in the present paper explore the significant insights of imidazolium-based ionic liquids as novel extractant for extractive desulfurization of liquid fuels. PMID- 26139407 TI - Determination of the psychoactive drugs carbamazepine and diazepam in hospital effluent and identification of their metabolites. AB - This study addresses the occurrence of carbamazepine and diazepam and their metabolites in the wastewater of the University Hospital (HUSM) of the Federal University of Santa Maria, RS-Brazil. Samples were collected from three sampling points of the sewage treatment system: point A ('emergency effluent'), point B ('general effluent') and point C ('water course-receptor'). Eight metabolites were identified: carbamazepine-10-11-epoxide, 10-dihydro-carbamazepine, 2-OH carbamazepine, iminoquinone, acridone, nordiazepam, oxazepam and temazepam. The mean concentrations in the emergency, general effluent and water course-receptor were as follows: 433.0 +/- 4.7, 349.0 +/- 5.0 and 485.0 +/- 5.6 ng L(-1), for carbamazepine and 550.0 +/- 4.3, 441.0 +/- 7.9 and 586.6 +/- 9.3 ng L(-1), for diazepam, respectively. Liquid chromatography with electrospray ionization tandem mass spectrometry (LC-QqLIT-MS) proved to be a method fit-to-purpose. The determination of carbamazepine and diazepam, and the identification of active metabolites showing environmental persistence (carbamazepine-10-11-epoxide, nordiazepam and oxazepam) revealed the need for a more effective treatment of the HUSM effluent. As far as we know, no similar study has been carried out on the wastewater of Brazilian hospitals. PMID- 26139408 TI - Polychlorinated biphenyls and organochlorine pesticides in atmospheric particulate matter of Northern China: distribution, sources, and risk assessment. AB - The objectives of this work are to track the contamination levels, distribution characteristics, and sources of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in atmospheric particulate matter (APM) of Northern China and to provide more comprehensive and fundamental data for risk assessment of organochlorine contaminants (OCs) in environments. Samples were extracted and purified by the microwave-assisted extraction and solid-phase extraction system, respectively. PCBs and OCPs were analyzed by gas chromatograph mass spectrometer. The concentrations of SigmaPCBs and SigmaOCPs ranged from 0.73 to 112.65 ng/g and 0.14 to 34.73 ng/g, respectively. PCBs in atmospheric particulates collected from Shijiazhuang City had the highest concentration, whereas OCP congeners were at the relatively low levels. However, the highest concentration of OCPs occurred in Yongning City. The principal component analysis indicated that the predominant compositions of PCBs in most of samples were tetrachlorobiphenyl (Tetra-CB), pentachlorobiphenyl (Penta-CB), hexachlorobiphenyl (Hexa-CB), and heptachlorbiphenyl (Hepta-CB), while hexachlorocyclohexanes (HCHs), DDTs, chlordanes, and endosulfans were the dominant components of OCPs, which was attributed to their application characteristics. OCs in those particles were further used to assess a potential cancer risk to humans via ingestion, dermal contact, and inhalation. Cancer risk was evaluated in airborne particles caused by PCBs and OCPs. TEQPCBs values suggested that the representative areas were subject to different pollution degrees. However, the pollution of OCPs in certain areas should be a concern due to 41.6% of the high risk, which could pose a potential risk to organisms. PMID- 26139409 TI - Characterization of the precursors of trihalomethanes and haloacetic acids in the Yuqiao Reservoir in China. AB - To identify the primary precursors of trihalomethanes and haloacetic acids in the Yuqiao Reservoir in China, dissolved organic matters in the source water were isolated and fractionated into five different fractions (with XAD resin), and both trihalomethane and haloacetic acid formation potentials in each fraction were analysed by liquid-liquid extraction and GC-ECD. The primary precursors of trihalomethanes and haloacetic acids were identified using the index of disinfection by-product formation potential and specific disinfection by-product formation potential. In addition, the relationship between the specific ultraviolet absorbance and the specific disinfection by-product formation potential was studied using correlation analysis. The results indicated that during the sampling period, the hydrophobic acids and hydrophilic matter are the primary organic fractions in the Yuqiao Reservoir, accounting for 27.6-40.9% and 21.2-32.5%, respectively. Among the five fractions, the hydrophobic acids had the highest disinfection by-product formation potential and specific disinfection by product formation potential, indicating that the hydrophobic acids were the primary precursors of the disinfection by-products in the Yuqiao Reservoir. A correlation analysis indicates that the specific ultraviolet absorbance had a moderately positive correlation with the specific disinfection by-product formation potential; therefore, the specific ultraviolet absorbance can be a reference index to analyse the ability of organic matter to generate disinfection by-products. PMID- 26139410 TI - Earthworms modify microbial community structure and accelerate maize stover decomposition during vermicomposting. AB - In the present study, maize stover was vermicomposted with the epigeic earthworm Eisenia fetida. The results showed that, during vermicomposting process, the earthworms promoted decomposition of maize stover. Analysis of microbial communities of the vermicompost by high-throughput pyrosequencing showed more complex bacterial community structure in the substrate treated by the earthworms than that in the control group. The dominant microbial genera in the treatment with the earthworms were Pseudoxanthomonas, Pseudomonas, Arthrobacter, Streptomyces, Cryptococcus, Guehomyces, and Mucor. Compared to the control group, the relative abundance of lignocellulose degradation microorganisms increased. The results indicated that the earthworms modified the structure of microbial communities during vermicomposting process, activated the growth of lignocellulose degradation microorganisms, and triggered the lignocellulose decomposition. PMID- 26139411 TI - Mn/Ti-doped carbon xerogel for efficient catalysis of microcystin-LR degradation in the water surface discharge plasma reactor. AB - The novel catalysts of Mn/Ti-doped carbon xerogel (CX) were synthesized for efficient degradation of microcystin-LR (MC-LR) in the water surface discharge plasma reactor. The degradation efficiency of 79.7% was obtained in 6 min with 0.5 wt% Ti impregnation of CX, and it would be increased with higher amount of Ti. In particular, Mn-doped CX resulted in larger mesoporous particle diameter and higher porosity in the matrix, and thereby, the highest efficiency of 88.6% was achieved for CX-Ti-Mn. The possible degradation pathway of MC-LR was elucidated on the basis of the LC-MS analysis. It demonstrated that Adda chain was cleaved from the MC-LR cyclic peptide by OH radical attack after plasma discharge in the presence of catalysts, and the generated nontoxic products can be further easily degraded in the biological treatment. Therefore, Mn/Ti-doped carbon xerogel is promising as the catalyst for the improvement of MC-LR degradation in the water surface discharge plasma reactor. PMID- 26139412 TI - Insecticidal potency of Aspergillus terreus against larvae and pupae of three mosquito species Anopheles stephensi, Culex quinquefasciatus, and Aedes aegypti. AB - Microbial control agents offer alternatives to chemical pest control, as they can be more selective than chemical insecticides. The present study evaluates the mosquito larvicidal and pupicidal potential of fungus mycelia using ethyl acetate and methanol solvent extracts produced by Aspergillus terreus against Anopheles stephensi, Culex quinquefasciatus, and Aedes aegypti. The A. terreus mycelia were extracted after 15 days from Sabouraud dextrose broth medium. The ethyl acetate extracts showed lethal concentration that kills 50% of the exposed larvae (LC50) and lethal concentration that kills 90% of the exposed larvae (LC90) values of the first, second, third, and fourth instar larvae of An. stephensi (LC50 = 97.410, 102.551, 29.802, and 8.907; LC90 = 767.957, 552.546, 535.474, and 195.677 MUg/ml), Cx. quinquefasciatus (LC50 = 89.584, 74.689, 68.265, and 67.40; LC90 = 449.091, 337.355, 518.793, and 237.347 MUg/ml), and Ae. aegypti (LC50 = 83.541, 84.418, 80.407, and 95.926; LC90 = 515.464, 443.167, 387.910, and 473.998 MUg/ml). Pupicidal activity of mycelium extracts was tested against An. stephensi (LC50 = 25.228, LC90 = 140.487), Cx. quinquefasciatus (LC50 = 54.525, LC90 = 145.366), and Ae. aegypti (LC50 = 10.536, LC90 = 63.762 MUg/ml). At higher concentration (500 MUg/ml), mortality starts within the first 6 h of exposure. One hundred percent mortality occurs at 24-h exposure. The overall result observed that effective activity against selected mosquito larvae and pupae after 24 h was a dose and time-dependent activity. These ensure that the resultant mosquito population reduction is substantial even where the larvicidal and pupicidal potential is minimal. The FTIR spectra of ethyl acetate extract reflect prominent peaks (3448.32, 3000.36, 2914.59, 2118.73, 1668.21, 1436.87, 1409.02, 954.33, 901.13, and 704.67 cm(-1)). The spectra showed a sharp absorption band at 1314.66 cm(-1) assigned to wagging vibration of the C-H group. The band at 1023.59 cm(-1) developed for C-O and C=N, respectively, and was commonly found in carboxylic acid and amine groups. GC-MS analysis of ethyl acetate extracts showed the presence of six compounds, of which the major compounds were identified as n hexadecanoic acid (15.31%) and methyl 12,15-octadecadienoate (31.989%), based on their peak molecular weight. The HPLC analysis result highlights that the A. terreus ethyl acetate extract was compared with pure n-hexadecanoic acid which resulted in similar retention time of 19.52 and 19.38, respectively. Thus, the active compound produced by this species would be more useful against vectors responsible for diseases of public health importance. This is the first report on mosquito larvicidal and pupicidal activity of ethyl acetate extract produced by A. terreus species. PMID- 26139413 TI - Advanced Proteogenomic Analysis Reveals Multiple Peptide Mutations and Complex Immunoglobulin Peptides in Colon Cancer. AB - Aiming toward an improved understanding of the regulation of proteins in cancer, recent studies from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) have focused on analyzing cancer tissue using proteomic technologies and workflows. Although many proteogenomics approaches for the study of cancer samples have been proposed, serious methodological challenges remain, especially in the identification of multiple mutational variants or structural variations such as fusion gene events. In addition, although immune system genes play an important role in cancer, identification of IgG peptides remains challenging in proteomic data sets. Here, we describe an integrative proteogenomic method that extends the limit of proteogenomic searches to identify multiple variant peptides as well as immunoglobulin gene variations/rearrangements using customized mining of RNA-seq data. Our results also provide the first extensive characterization of tumor immune response and demonstrate the potential of this method to improve the molecular characterization of tumor subtypes. PMID- 26139416 TI - A rare cause of tonsillar asymmetry. PMID- 26139414 TI - DANTE-prepared three-dimensional FLASH: A fast isotropic-resolution MR approach to morphological evaluation of the peripheral arterial wall at 3 Tesla. AB - BACKGROUND: To develop and assess a sequence using DANTE dark-blood preparation combined with FLASH readout (DANTE-FLASH) for rapid isotropic-resolution three dimensional (3D) peripheral vessel wall imaging at 3 Tesla (T). METHODS: Numerical simulations were first conducted to optimize imaging parameters for maximizing the wall-lumen contrast. The sequence, implemented at 3T, was then assessed in the bilateral superficial femoral arteries of eight healthy volunteers and three patients who were undergoing non-contrast-enhanced MRA due to known peripheral artery disease. Conventional 2D dark-blood turbo spin echo (DB-TSE) was performed as a reference in all subjects. Image quality on a 5-point scale, apparent wall signal-to-noise ratio, apparent wall-lumen contrast-to-noise ratio, wall thickness, wall area and lumen area were assessed or measured in all healthy subjects. Additionally, the agreement in the depiction of wall thickening or luminal stenosis between DANTE-FLASH and DB-TSE, or MRA was assessed using a 4 point scale in the patient study. RESULTS: DANTE-FLASH allowed for a 30-cm-long coverage within 4 min, whereas DB-TSE took approximately 7 min for a 9-cm-long coverage. Good image quality was obtained by DANTE-FLASH (score > 3). The wall thickness, wall area, and lumen area were all comparable (t-test; P = 0.334, 0.224 and 0.136) and showed excellent agreement between DANTE-FLASH and DB-TSE (intra-class correlation = 0.81, 0.85, and 0.98). The atherosclerotic plaques and luminal stenosis identified by DANTE-FLASH were in accordance with the findings by 2D DB-TSE or MRA. CONCLUSION: DANTE-FLASH is a 3D dark-blood MR sequence allowing for rapid isotropic-resolution imaging of the peripheral vessel wall at 3T. PMID- 26139415 TI - Guidelines (short version) of the French Otorhinolaryngology - Head and Neck Surgery Society (SFORL) on patient pathway organization in ENT: The therapeutic decision-making process. AB - OBJECTIVES: The authors present the guidelines of the French Otorhinolaryngology Head and Neck Surgery Society (SFORL) for patient pathway organization in head and neck cancer, and in particular for multidisciplinary team meetings. The present article concerns the therapeutic decision-making process. METHODS: A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. RESULTS: It is recommended that: an organ specialist should contribute to all multidisciplinary meetings on head and neck cancer; all members of the multidisciplinary meeting should have specific knowledge in head and neck cancer; any referring physician who does not follow the multidisciplinary meeting's advice should justify that decision; there should be sufficient time to prepare, discuss and sum up the cases dealt with in the multidisciplinary team meeting. PMID- 26139417 TI - Cervicofacial cellulitis: The impact of non-steroidal anti-inflammatory drugs. A study of 70 cases. AB - INTRODUCTION: Cervicofacial cellulitis (CFC) is a severe infection of the subcutaneous cellular tissue, and is one of the most serious head and neck infectious emergencies. In a series of 70 cases treated between 2007 and 2012, we noticed a strong correlation between use of non-steroidal anti-inflammatory drugs (NSAIDs) and evolution of head and neck infections toward CFC, including two cases of necrotic CFC extending to the mediastinum, which were fatal. MATERIAL AND METHODS: The cases included in the series comprised patients admitted to emergency and requiring hospitalization due to the severity of presenting symptoms. There were 70 such cases of CFC between 2007 and 2012; cases managed on an outpatient basis were excluded, as were cases of orbital CFC, CFC of sinus origin and mastoiditis. RESULTS: Eighty percent of patients took NSAIDs, on self medication or by prescription (community physician, dentist, pharmacist). The most frequent molecules were tiaprofenic acid and diclofenac. CFC extension was restricted in most cases to the maxillary and/or ipsilateral subhyoid region, with 5 cases of lower cervical extension and 2 of mediastinal involvement, which both proved fatal. CONCLUSION: CFC is a severe infection that can be life threatening, and represents a diagnostic and therapeutic emergency. Among other risk factors, use of NSAIDs is frequently reported; these should therefore be used with caution if at all in head and neck infection, especially of odonto stomatological origin. PMID- 26139418 TI - Recurrent nonconvulsive status epilepticus in a patient with progressive left hemispheric leukoencephalopathy after a remote viral meningoencephalitis. AB - Nonconvulsive status epilepticus (NCSE), defined as changes in behavior and/or mental processes from baseline with continuous epileptiform discharges, remains a diagnostic and treatment challenge. Here, we present a 68-year-old female who developed 3 episodes of NCSE 10 years after a viral meningoencephalitis which gradually progressed to left hemispheric leukoencephalopathy. In this case, we hypothesize that immune-mediated mechanisms and perhaps genetic predisposition played a role in epileptogenesis, and these will be discussed. This article is part of a Special Issue entitled "Status Epilepticus". PMID- 26139419 TI - Systemic mechanisms of antiepileptic protection. AB - AIM: The objectives of this study were as follows: (1) to explore mechanisms that counteract epileptogenesis and provide antiepileptic protection in the life threatening condition of status epilepticus; and (2) to access functional state of adaptation system and identify the roles of biochemical, humoral, and neurophysiologic factors in the antiepileptic protective system. METHODS: The experimental part of this research included a series of experiments using animal models which studied the influence of apnea (hypoxia and hypercapnia) on seizure activity; in addition, the role of the prefrontal and orbitofrontal cortex in epileptogenesis and antiepileptogenesis was explored. The clinical part consisted of a series of neurophysiological studies, using a method of multistage dipole localization, and clinical models of absence epilepsy and a tumor in the Rolandic region. One more line of clinical investigations was the study of the functional state of the adaptation system. Thirty-one patients with status epilepticus, with ages 14-56, were recruited. Proteins and fractions, electrolytes, acid-base balance, and 17-oxycorticosteroids in the blood plasma and 17-21-dioxy-20 ketosteroids in the urine were examined in relation to clinical data, EEG, and MRI. RESULTS: As a result of the experiments, it was determined that asphyxia has a two-phase impact on spike activity; an anticonvulsive effect of asphyxia is mediated by hypercapnia, while the orbitofrontal cortex plays the key role in the system of antiepileptic protection through its inhibition of other structures. Further, the mediobasal prefrontal lobe of the dominant hemisphere plays a significant role in antiepileptic protection, and increased levels of blood 17 corticosteroids and catecholamines are protective in the setting of stress from convulsive status epilepticus. CONCLUSIONS: The system of antiepileptic protection includes humoral, biochemical, and neurophysiological mechanisms. We identified the roles of all these factors: hypercapnia, in connection with tonic convulsion, as the humoral factor and inhibitory potential of the prefrontal lobe as the main neurophysiologic factor. In the setting of convulsive status epilepticus, which maximally strains these adaptations, it is essential for endogenous levels of glucocorticoids (17-corticosteroid) and sympathoepinephrine to increase. This article is part of a Special Issue entitled "Status Epilepticus". PMID- 26139420 TI - Long-term follow-up of the risk for cervical intraepithelial neoplasia grade 2 or worse in HPV-negative women after conization. AB - Little research has been conducted on the long-term value of human papillomavirus (HPV) testing after conization. We investigated whether cytology adds to the value of a negative HPV test for long-term prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In addition, we compared risk of CIN2+ following a negative HPV test in women after conization with that in women from the general population. During 2002-2005, 667 women treated for CIN2+ were tested for HPV and cytology 46 months after conization. Only HPV-negative women were included. Women participating in routine screening were age-matched with post conization HPV-negative women, leaving 13,230 and 477 women, respectively, for analysis. By linkage to the Pathology Data Bank, we identified all cases of CIN2+ by December 2013. The 3-, 5-, 8- and 10-year risks for CIN2+ were 0.7, 0.9, 2.8 and 5.7% after a negative HPV test and 0.5, 0.8, 2.9 and 6.1% in HPV and cytology negative women. HPV-negative women in the general population had similar 3-year and 5-year risks of 0.4 and 1.0%; thereafter, they had lower risks of 1.9% at 8 years and 2.7% at 10 years. Our results indicate that HPV testing may be used as a test of cure after conization. In the first 5 years after testing, the risk for CIN2+ of women who were HPV-negative at 34 months after conization was similar to that of HPV-negative women in the general population. After 67 years, however, women who have undergone conization may be at higher risk for CIN2+. PMID- 26139421 TI - Cost and threshold analysis of positive charge, a multi-site linkage to HIV care program in the United States. AB - Positive Charge (PC) is a linkage to HIV care initiative implemented by AIDS United with sites in New York, Chicago, Louisiana, North Carolina, and the San Francisco/Bay Area. This study employed standard methods of cost and threshold analyses, as recommended by the US Panel on Cost-effectiveness in Health and Medicine, to calculate cost-saving and cost effective thresholds of the initiative. The overall societal cost of the linkage to care programs ranged from $48,490 to $370,525. The study found that PC's five unique evidence-based linkage to care programs have relatively low costs per client served and highly achievable cost-saving and cost-effectiveness thresholds. The findings from this study suggest that HIV linkage to care programs have the potential to be a highly productive use of public health resources. PMID- 26139422 TI - Nested Event-Level Case-Control Study of Drug Use and Sexual Outcomes in Multipartner Encounters Reported by Men Who Have Sex with Men. AB - Previous event-level analyses have often, but not always, found significant associations between drug use and sexual risk behaviour in men who have sex with men (MSM), but these analyses have rarely considered either multipartner encounters specifically, or other sexual outcomes such as pleasure and control. Using data from an internet-based longitudinal survey of MSM, we tested the association between drug use by respondent and by partners and unprotected anal intercourse (UAI), pleasure and control over sexual activity. Overall respondent substance use was significantly associated with increased odds of UAI, though not with pleasure or control. Respondent use of crystal methamphetamine was significantly associated with both increased odds of UAI and decreased odds of control over sexual activity. This analysis agrees with previous studies of dyadic encounters, and specifically suggests that the association between crystal methamphetamine and sexual risk behaviour may be mediated by loss of control. PMID- 26139423 TI - Southern Monarchs do not Develop Learned Preferences for Flowers With Pyrrolizidine Alkaloids. AB - Danaus butterflies sequester pyrrolizidine alkaloids (PAs) from nectar and leaves of various plant species for defense and reproduction. We tested the hypothesis that the southern monarch butterfly Danaus erippus shows innate preferences for certain flower colors and has the capacity to develop learned preferences for artificial flowers presenting advantageous floral rewards such as PAs. We predicted that orange and yellow flowers would be innately preferred by southern monarchs. Another prediction is that flowers with both sucrose and PAs would be preferred over those having sucrose only, regardless of flower color. In nature, males of Danaus generally visit PA sources more often than females, so we expected that males of D. erippus would exhibit a stronger learned preference for PA sources than the females. In the innate preference tests, adults were offered artificial non-rewarding yellow, orange, blue, red, green, and violet flowers. Orange and yellow artificial flowers were most visited by southern monarchs, followed by blue and red ones. No individual visited either green or violet flowers. For assessing learned preferences for PA flowers over flowers with no PAs, southern monarchs were trained to associate orange flowers with sucrose plus the PA monocrotaline vs. yellow flowers with sucrose only; the opposite combination was used to train another set of butterflies. In the tests, empty flowers were offered to trained butterflies. Neither males nor females showed learned preferences for flower colors associated with PAs in the training set. Thus, southern monarchs resemble the sister species Danaus plexippus in their innate preferences for orange and yellow flowers. Southern monarchs, similarly to temperate monarchs, might not be as PA-demanding as are other danaine species. PMID- 26139424 TI - Editorial: the vital role of randomized controlled trials in Arthritis & Rheumatology. PMID- 26139426 TI - Anti-mullerian hormone (AMH) is associated with natural menopause in a population based sample: The CARDIA Women's Study. AB - OBJECTIVE: AMH is associated with menopausal timing in several studies. In contrast to prior studies that were restricted to women with regular cycles, our objective was to examine this association in women with either regular or irregular menstrual cycles. METHODS: CARDIA is a longitudinal, population-based study that recruited adults ages 18-30 when it began in 1985-1986. AMH was measured in serum stored in 2002-2003. Natural menopause was assessed by survey in 2005-2006 and 2010-2011. RESULTS: Among 716 premenopausal women, median [25th, 75th] AMH was 0.77 [0.22-2.02]ng/dL at a median age of 42 [39-45] years. Twenty nine percent of the women (n=207) reported natural menopause during 9 years of follow up. In fully adjusted discrete-time hazard models, a 0.5 ng/dL AMH decrement was associated with higher risk of menopause (p<0.001). Hazard ratios varied with time since AMH measurement. The HR (95% CI) for menopause was 8.1 (2.5-26.1) within 0-3 years and 2.3 (1.7-3.3) and 1.6 (1.3-2.1) for 3-6 and 6-9 years, respectively. When restricted to women with regular menses, results were similar (e.g., HR=6.1; 95% CI: 1.9-20.0 for 0-3 years). CONCLUSION: AMH is independently associated with natural menopause. AMH appears most useful in identifying women at risk of menopause in the near future (within 3 years of AMH measurement). PMID- 26139425 TI - Potential Causes and Present Pharmacotherapy of Irritable Bowel Syndrome: An Overview. AB - BACKGROUND: Irritable bowel syndrome (IBS) is currently one of the most common disorders of the digestive system in the Western society. Almost 2 out of 10 people suffer from IBS with women being more affected than men. IBS is associated with abdominal pain, bloating and altered stool consistency and imposes a heavy burden for the affected patients. SUMMARY: The pathophysiology of IBS remains elusive although potential causes have been suggested, such as a deranged brain gut signaling, hypersensitivity of visceral sensory afferent fibers, bacterial gastroenteritis, small intestinal bacterial overgrowth (SIBO), genetic alterations and food sensitivity. Targets for the pharmacotherapy of IBS include the serotonergic and opioidergic system, and the microbial population of the gut. Alternative therapies like traditional Chinese medicine have shown some success in the combat against IBS. Key Messages: Many therapeutics for the treatment of IBS have emerged in the past; however, only a few have met up with the expectations in larger clinical trials. Additionally, the multifactorial etiology of IBS and its variety of cardinal symptoms requires an individual set of therapeutics. This review provides a short overview of potential causes and current pharmacological therapeutics and of additional and alternative therapies for IBS. PMID- 26139427 TI - Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia. AB - We examined the combination of the mammalian target of rapamycin inhibitor everolimus with bortezomib and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM) in a phase I/II study. All patients received six cycles of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab followed by maintenance with everolimus until progression. Forty-six patients were treated; 98% received prior rituximab and 57% received prior bortezomib. No dose-limiting toxicities were observed in the phase I. The most common treatment-related toxicities of all grades were fatigue (63%), anemia (54%), leucopenia (52%), neutropenia (48%) and diarrhea (43%). Thirty-six (78%) of the 46 patients received full dose therapy (FDT) of the three drugs. Of these 36, 2 (6%) had complete response (90% confidence interval (CI): 1 16). In all, 32/36 (89%) of patients experienced at least a minimal response (90% CI: 76-96%). The observed partial response or better response rate was 19/36 (53, 90 CI: 38-67%). For the 36 FDT patients, the median progression-free survival was 21 months (95% CI: 12-not estimable). In summary, this study demonstrates that the combination of everolimus, bortezomib and rituximab is well tolerated and achieved 89% response rate even in patients previously treated, making it a possible model of non-chemotherapeutic-based combination therapy in WM. PMID- 26139428 TI - Ibrutinib selectively targets FLT3-ITD in mutant FLT3-positive AML. PMID- 26139429 TI - The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells. AB - Interleukin (IL)-10-producing B cells (B10 cells) have emerged as important regulatory elements with immunosuppressive roles. Chronic lymphocytic leukemia (CLL) B cells also secrete IL-10 and share features of B10 cells, suggesting a possible contribution of CLL B cells to immunosuppression in CLL patients. Factors controlling the emergence of B10 cells are not known. B-cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) is critical for B-cell maturation and survival, and is implicated in the development and progression of CLL. We sought to investigate the role of BAFF in the emergence of IL-10 producing regulatory B cells in healthy donors and CLL patients. Here, we report that BAFF signaling promotes IL-10 production by CLL B cells in a mouse model of CLL and in CLL patients. Moreover, BAFF-mediated IL-10 production by normal and CLL B cells is mediated via its receptor transmembrane activator and cyclophilin ligand interactor. Our work uncovered a major targetable pathway important for the generation of regulatory B cells that is detrimental to immunity in CLL. PMID- 26139430 TI - Multiplexed targeted sequencing of recurrent fusion genes in acute leukaemia. PMID- 26139431 TI - Total hip arthroplasty in an outpatient setting in 27 selected patients. AB - BACKGROUND AND PURPOSE: As a result of introduction of a fast-track program, length of hospital stay after total hip arthroplasty (THA) decreased in our hospital. We therefore wondered whether THA in an outpatient setting would be feasible. We report our experience with THA in an outpatient setting. PATIENTS AND METHODS: In this prospective cohort study, we included 27 patients who were selected to receive primary THA in an outpatient setting between April and July 2014. Different patient-reported outcome measures (PROMs) were recorded preoperatively and at 6 weeks and 3 months postoperatively. Furthermore, anchor questions on how patients functioned in daily living were scored at 6 weeks and 3 months postoperatively. RESULTS: 3 of the 27 patients did not go home on the day of surgery because of nausea and/or dizziness. The remaining 24 patients all went home on the day of surgery. PROMs improved substantially in these patients. Moreover, anchor questions on how patients functioned in their daily living indicated that the patients were satisfied with the postoperative results. 1 re admission occurred at 11 days after surgery because of seroma formation. There were no other complications or reoperations. INTERPRETATION: At our hospital, with a fast-track protocol, outpatient THA was found to be feasible in selected patients with satisfying results up to 3 months postoperatively, without any outpatient procedure-specific complications or re-admissions. PMID- 26139432 TI - A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion. AB - CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98-100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection. PMID- 26139433 TI - Post-traumatic stress disorder and the obstetric anaesthetist. PMID- 26139434 TI - Chiral Memory in Silylium Ions. AB - The configurational stability of the chiral silicon center in Lewis base stabilized silyliums has been studied. Complete retention of configuration at silicon is observed at low temperature in silylium ions stabilized by lone-pair interactions. In contrast, loss of chiral memory is observed with systems involving pi-interactions. Epimerization of the silicon center was observed by simply allowing equilibration of the diastereomeric silyliums at RT or by adding a catalytic amount of a chelating solvent. Conditions for the transfer of axial chirality to Si-centered chirality were shown to rely on the strength of the Lewis base-silylium ion interaction. PMID- 26139435 TI - Pump up the volume: could excessive neural gain explain tinnitus and hyperacusis? AB - Naturally occurring stimuli can vary over several orders of magnitude and may exceed the dynamic range of sensory neurons. As a result, sensory systems adapt their sensitivity by changing their responsiveness or 'gain'. While many peripheral adaptation processes are rapid, slow adaptation processes have been observed in response to sensory deprivation or elevated stimulation. This adaptation process alters neural gain in order to adjust the basic operating point of sensory processing. In the auditory system, abnormally high neural gain may result in higher spontaneous and/or stimulus-evoked neural firing rates, and this may have the unintended consequence of presenting as tinnitus and/or sound intolerance, respectively. Therefore, a better understanding of neural gain, in health and disease, may lead to more effective treatments for these aberrant auditory perceptions. This review provides a concise summary of (i) evidence for changes in neural gain in the auditory system of animals, (ii) physiological and perceptual changes in adult human listeners following an acute period of enhanced acoustic stimulation and/or deprivation, (iii) physiological evidence of excessive neural gain in tinnitus and hyperacusis patients, and (iv) the relevance of neural gain in the clinical treatment of tinnitus and hyperacusis. PMID- 26139436 TI - The indication area of a diagnostic test. Part I--discounting gain and loss in diagnostic certainty. AB - OBJECTIVES: Test performance is conventionally expressed by gain in diagnostic certainty. We propose net diagnostic gain and indication area as more appropriate measures of test performance; then, the loss in certainty due to misclassification and the information of "no test" would be performed are taken into account. STUDY DESIGN AND SETTING: A decision analytical model was developed in which two alternative strategies were compared: testing and no testing. Correct diagnostic test results received a positive value; undesired test results received a negative value. Within the "no test" scenario, it was assumed that physicians are more prone to treat as the probability of disease is higher. RESULTS: Discounting gain and loss in diagnostic certainty results in a concave function of the prior. The indication area is the range of priors with a net diagnostic gain; testing is deleterious beyond this range. The net diagnostic gain reaches a maximum at a specific prior. A freely available Web site-based calculator was developed for easy calculation of the indication area and the maximum diagnostic gain for each combination of sensitivity and specificity. CONCLUSION: Medical testing is not indicated when the prior disease probabilities are low (as to screening for a condition) or high (for diagnostic confirmation). PMID- 26139437 TI - Response to letter by Frane: "False discovery rate control is not always a replacement for Bonferroni-type adjustment". PMID- 26139438 TI - Novel Heterozygous Mutations of NR5A1 and Their Functional Characteristics in Patients with 46,XY Disorders of Sex Development without Adrenal Insufficiency. AB - BACKGROUND/AIMS: Heterozygous mutations of NR5A1, which encodes steroidogenic factor 1 (SF1), were identified in patients with 46,XY disorders of sex development (DSD) with normal adrenal function. This study was aimed to identify and functionally characterize mutations of NR5A1 in patients with 46,XY DSD. METHODS: This study included 51 patients from 49 unrelated families with 46,XY DSD. Genomic DNA was extracted from peripheral blood leukocytes, and direct sequencing of all coding exons and their flanking introns of NR5A1 was performed. Transient transfections and dual-luciferase(r) reporter assays were performed to evaluate the effect of NR5A1 variants on transcriptional activity. RESULTS: Four of 49 patients (8.2%) harbored a novel heterozygous sequence variant of NR5A1: c.80G>C (p.G26A), c.847T>C (p.C283R), c.1151del (p.L384Rfs*7), and c.1333G>T (p.E445*). They presented with female external genitalia with clitoromegaly in infancy or childhood, or primary amenorrhea in adolescence. In vitro functional studies of SF1 activity determined that each variant, except p.E445*, led to a reduced expression of downstream target genes and disturbed the regulation of gonadal development. CONCLUSIONS: Loss-of-function mutations of NR5A1 are a relatively common cause of 46,XY DSD. Therefore, genetic defects of NR5A1 should be considered as an etiology in subjects with 46,XY DSD without adrenal insufficiency. PMID- 26139439 TI - Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort Study. AB - Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence interval [95% CI], 293-533) and 323 (95% CI, 216-481) fractures per 10,000 person-years, respectively. These rates were 2- to 3-fold higher than published general population rates. The only gender difference in fracture risk was a 2.6-fold higher risk in males aged >=15 years (570/10,000 person-years, adjusted P=0.04). In multivariable analysis, advanced pubertal stage, greater height Z-score, difficulty walking, and higher average log-transformed parathyroid hormone level were independently associated with greater fracture risk (all P<=0.04). Phosphate binder treatment (predominantly calcium-based) was associated with lower fracture risk (hazard ratio, 0.37; 95% CI, 0.15-0.91; P=0.03). Participation in more than one team sport was associated with higher risk (hazard ratio, 4.87; 95% CI, 2.21-10.75; P<0.001). In conclusion, children with CKD have a high burden of fracture. Regarding modifiable factors, higher average parathyroid hormone level was associated with greater risk of fracture, whereas phosphate binder use was protective in this cohort. PMID- 26139440 TI - Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease. AB - Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function. PMID- 26139441 TI - Recall of provision of sun protection measures to patients with cystic fibrosis being prescribed voriconazole. PMID- 26139442 TI - Response to article - S Seang et al. Long-term follow-up of HIV-infected patients once diagnosed with acyclovir-resistant herpes simplex virus (Int J STD AIDS 2014; 25: 676-682). PMID- 26139443 TI - Response to article - R Dabis et al. Do attendees at sexual health and HIV clinics prefer to be called in by name or number? (Int J STD AIDS 2014; 25: 511 515). PMID- 26139444 TI - Response to article - R Dabis et al. Do attendees at sexual health and HIV clinics prefer to be called in by name or number? (Int J STD AIDS 2014; 25: 511 515). PMID- 26139445 TI - Retrieving spin textures on curved magnetic thin films with full-field soft X-ray microscopies. AB - X-ray tomography is a well-established technique to characterize 3D structures in material sciences and biology; its magnetic analogue--magnetic X-ray tomography- is yet to be developed. Here we demonstrate the visualization and reconstruction of magnetic domain structures in a 3D curved magnetic thin films with tubular shape by means of full-field soft X-ray microscopies. The 3D arrangement of the magnetization is retrieved from a set of 2D projections by analysing the evolution of the magnetic contrast with varying projection angle. Using reconstruction algorithms to analyse the angular evolution of 2D projections provides quantitative information about domain patterns and magnetic coupling phenomena between windings of azimuthally and radially magnetized tubular objects. The present approach represents a first milestone towards visualizing magnetization textures of 3D curved thin films with virtually arbitrary shape. PMID- 26139446 TI - Development of a Generic Anti-PEG Antibody Assay Using BioScale's Acoustic Membrane MicroParticle Technology. AB - Immunogenicity testing for PEGylated biotherapeutics should include methods to detect both anti-protein and anti-PEG antibodies (anti-PEG). Although some methods have been published for the detection of anti-PEG antibodies, the information is incomplete and, in some cases, reagents used (such as Tween-20) are known to interfere with detection. This rapid communication describes the use of BioScale's Acoustic Membrane MicroParticle (AMMP(r)) technology using the ViBE(r) Workstation to measure anti-PEG antibodies in human serum samples. Briefly, a sample spiked with monoclonal human IgG anti-PEG antibody is diluted in buffer and incubated with paramagnetic beads coated with linear chain mPEG to capture anti-PEG antibodies. The complex is then captured on an acoustic membrane coated with Protein A. The change in mass on the membrane caused by the binding of the complex to the membrane results in a signal proportional to the mass of anti-PEG antibodies. The data indicate that an assay with a sensitivity of less than 1000 ng/mL for IgG is achievable. This level of sensitivity is better than current published reports on IgG anti-PEG antibody detection. PMID- 26139447 TI - Goals and Social Comparisons Promote Walking Behavior. AB - The effectiveness of a pedometer intervention was affected by manipulating the goals given to participants and by providing social comparison feedback about how participants' performance compared with others. In study 1 (n= 148), university staff members received a low, medium, or high walking goal (10%, 50%, or 100% increase over baseline walking). Participants walked 1358 more steps per day (95% confidence interval [CI], 729, 1985), when receiving a high goal than when receiving a medium goal, but a medium goal did not increase walking relative to a low goal (554 more steps; 95% CI, -71,1179). In study 2 (n= 64), participants received individual feedback only or individual plus social comparison feedback. Participants walked 1120 more steps per day (95% CI, 538, 1703) when receiving social comparison feedback than when receiving only individual feedback. Goals and the performance of others act as reference points and influence the effect that pedometer feedback has on walking behavior, illustrating the applicability of the principles of behavioral economics and social psychology to the design of health behavior interventions. PMID- 26139448 TI - A Decision Analysis of Percutaneous Left Atrial Appendage Occlusion Relative to Novel and Traditional Oral Anticoagulation for Stroke Prevention in Patients with New-Onset Atrial Fibrillation. AB - BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) is a nonpharmacologic approach for stroke prevention in nonvalvular atrial fibrillation (NVAF). No direct comparisons to novel oral anticoagulants (OACs) exists, limiting decision making on the optimal strategy for stroke prevention in NVAF patients. Addressing this gap in knowledge is timely given the recent debate by the US Food and Drug Administration regarding the effectiveness of LAAO. OBJECTIVE: To assess the cost-effectiveness of LAAO and novel OACs relative to warfarin in patients with new-onset NVAF without contraindications to OAC. DESIGN: A cost-utility analysis using a patient-level Markov micro-simulation decision analytic model was undertaken to determine the lifetime costs, quality adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of LAAO and all novel OACs relative to warfarin. Effectiveness and utility data were obtained from the published literature and cost from the Ontario Drug Benefits Formulary and Case Costing Initiative. RESULTS: Warfarin had the lowest discounted QALY (5.13 QALYs), followed by dabigatran (5.18 QALYs), rivaroxaban and LAAO (5.21 QALYs), and apixaban (5.25 QALYs). The average discounted lifetime costs were $15 776 for warfarin, $18 280 for rivaroxaban, $19 156 for apixaban, $20 794 for dabigatran, and $21 789 for LAAO. Apixaban dominated dabigatran and LAAO and demonstrated extended dominance over rivaroxaban. The ICER for apixaban relative to warfarin was $28 167/QALY. Apixaban was preferred in 40.2% of simulations at a willingness-to-pay threshold of $50 000/QALY. LIMITATIONS: Assumptions regarding clinical and methodological differences between published studies of each therapy were minimized. CONCLUSIONS: Apixaban is the most cost effective therapy for stroke prevention in patients with new-onset NVAF without contraindications to OAC. Uncertainty around this conclusion exists, highlighting the need for further research. PMID- 26139449 TI - Quantifying Parameter Uncertainty in EQ-5D-3L Value Sets and Its Impact on Studies That Use the EQ-5D-3L to Measure Health Utility: A Bayesian Approach. AB - BACKGROUND: . Parameter uncertainty in EQ-5D value sets is routinely ignored. Sources of parameter uncertainty include uncertainty in the estimated regression coefficients of the scoring algorithm and uncertainty that arises from the need to use a nonsaturated functional form when creating the scoring algorithm. We hypothesize that this latter source is the major contributor to parameter uncertainty in the value sets. METHODS: . We used data from the United States EQ 5D-3L valuation study to assess the extent of parameter uncertainty in the value set. We refitted the US scoring algorithm to quantify contributors to the mean square prediction errors and used a Bayesian approach to estimate the predictive distribution of the mean utilities. The impact of parameter uncertainty in the value set was assessed using survey data. RESULTS: . Parameter uncertainty in the estimated regression coefficients explained 16% of the mean squared prediction error; uncertainty in the functional form explained the remaining 84%. The median width of the 95% credible intervals for the mean utilities was 0.15. In estimating mean utility in our survey population, parameter uncertainty in the value set was responsible for 93% of the total variance, with sampling variation in the survey population being responsible for the remaining 7%. CONCLUSION: . EQ 5D-3L value sets are estimated subject to considerable parameter uncertainty; the median credible interval width is large compared with reported values of the minimum important difference for the EQ-5D-3L, which have been reported to be as small as 0.03. Other countries' scoring algorithms are based on smaller studies and are hence subject to greater uncertainty. This uncertainty should be accounted for when using EQ-5D health utilities in economic evaluations. PMID- 26139450 TI - What does serum gamma-glutamyltransferase tell us as a cardiometabolic risk marker? AB - gamma-glutamyltransferase plays a key role in the synthesis and metabolism of extracellular glutathione, a major antioxidant in several defence mechanisms in the body. gamma-glutamyltransferase is affected by environmental and genetic factors, and is raised when there is depletion of glutathione. Hence, it is a marker of oxidative stress. There is robust evidence that gamma glutamyltransferase even when values are within the reference interval is associated with increased cardiovascular and all-cause mortality in both sexes, in normal subjects and subjects with coronary artery disease, in the middle-aged and the elderly after adjusting for confounding factors. gamma glutamyltransferase even within the reference interval is associated with future presentation of type 2 diabetes, and the longitudinal increase in gamma glutamyltransferase activity is associated with increased risk of type 2 diabetes and cardiovascular mortality. gamma-glutamyltransferase is associated with cardiovascular risk factors and metabolic syndrome. It has a prognostic value after a previous acute myocardial infarction and may be an indicator of adverse outcome in acute coronary syndromes and other chronic cardiac disorders. There is limited data about gamma-glutamyltransferase and any association with peripheral arterial disease and also whether knowing gamma-glutamyltransferase activity improves cardiovascular risk prediction beyond conventional risk factors. gamma glutamyltransferase is present in atherosclerotic lesions in the coronary and carotid arteries, and has a prooxidant role leading to the production of reactive oxygen species and atherosclerosis. Current reference intervals for gamma glutamyltransferase are inappropriate and need to be addressed. Some laboratories still use non- International Federation of Clinical Chemistry methods for estimation of gamma-glutamyltransferase which are associated with lower results. Such laboratories should review their method and consider changing to the International Federation of Clinical Chemistry method. PMID- 26139451 TI - Detecting cardiac events - state-of-the-art. AB - Cardiac biomarker measurement currently addresses two key questions in patient management: the differential diagnosis of chest pain and the differential diagnosis of the patient with breathlessness. There are currently three major themes in the strategies for the differential diagnosis of chest pain. The first is to undertake troponin measurement in patients selected to be at lower risk, hence to have a low prior probability of disease. The second is the introduction of high-sensitivity cardiac troponin (hs cTn) assays into routine clinical use with measurement at 0 and 3 h from admission. Two other approaches that utilize the diagnostic characteristics of these assays have also been suggested. The first is to use the limit of detection or limit of blank of the assay as the diagnostic discriminant. The second approach is to use the low imprecision of the assay within the reference interval and combine a discriminant value with an absolute rate of change (delta value). The third is the use of additional biomarkers to allow early discharge from the emergency department. The concept is to measure high-sensitivity cardiac troponin plus the extra marker on admission. The role of measurement of B-type natriuretic peptide or its N-terminal prohormone, N-terminal pro-B-type natriuretic peptide, has been accepted and incorporated into guidelines for chronic heart failure for some time. More recently, guidelines for acute heart failure can also recommend a single measurement of B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide in people presenting with new suspected acute heart failure. PMID- 26139452 TI - Epidemiology, Regional Characteristics, Knowledge, and Attitude Toward Female Genital Mutilation/Cutting in Southern Iran. AB - INTRODUCTION: Female genital mutilation/cutting (FGM/C), also known as female circumcision, is an ancient traditional procedure that involves partial or total removal of the female external genitalia for nonmedical reasons. Although it is well described in African and some Arabic countries, data from Iran are scarce. AIM: To describe the epidemiology, regional characteristics, knowledge, and attitude toward FGM/C in Southern Iran. METHODS: This cross-sectional study was conducted during a 36-month period from 2010 to 2013 in Hormozgan, a southern province of Iran near the Persian Gulf. We included 780 women in six major rural areas of the province who referred to healthcare centers for vaccination, midwifery, or family planning services. All participants underwent complete pelvic examination to determine the type of FGM. The questionnaire consisted of several sections such as demographic and baseline characteristics, and two self report sections addressing the knowledge and attitude toward FGM/C and its complications. Baseline sociodemographic characteristics including age, educational level, marital status, religion, and nationality were the independent variables. RESULTS: Among the participants, 535 (68.5%) had undergone FGM/C. FGM/C was associated with higher age (P = 0.002), Afghan nationality (P = 0.003), Sunni Islam as religion (P = 0.019), illiteracy (P < 0.001), and family history of FGM/C in mother (P < 0.001), sister (P < 0.001), and grandmother (P < 0.001). Ancient traditions in the area (57.1%) were mentioned as the most important factor leading to FMG/C. Urinary tract infection was the most common reported complication (60.4%). CONCLUSION: FGM/C is a common practice in rural areas of Southern Iran. It is associated with increased age, illiteracy, Sunni Islam religion, Afghan nationality, and positive family history. Lack of knowledge toward FGM/C is the main cause of its high prevalence and continuation in the area. PMID- 26139453 TI - Human Urinary Kallidinogenase Improves Outcome of Stroke Patients by Shortening Mean Transit Time of Perfusion Magnetic Resonance Imaging. AB - BACKGROUND: Improving cerebral perfusion remains a good option for ischemic stroke for restoring cerebral blood flow. Human urinary kallidinogenase has been shown promising in treating stroke patients. To investigate whether human urinary kallidinogenase's efficacy in treating stroke patients has relationship with improving cerebral perfusion and possible mechanism. METHODS: Fifty-eight stroke patients in Nanjing Drum Tower Hospital were enrolled in this prospective study. Of them, 29 received human urinary kallidinogenase, while the other 29 were selected as control. National institute health stroke scale, modified Rankin Scale and activities of daily living score were used to determine patient outcome. Cerebral perfusion in patients was determined by perfusion magnetic resonance imaging. Serum apelin and vascular endothelial growth factor were measured by enzyme-linked immunosorbent assay. RESULTS: We confirmed that human urinary kallidinogenase improved stroke outcome in patients. Cerebral perfusion was elevated by human urinary kallidinogenase 12 days after therapy. Human urinary kallidinogenase enhanced vascular endothelial growth factor and APJ expression in stroke patients. The reduced mean transit time was related with favorable outcome analyzed by univariate logistic regression. CONCLUSIONS: Human urinary kallidinogenase facilitated stroke recovery and enhanced cerebral reperfusion through up-regulating vascular endothelial growth factor, apelin/APJ pathway. PMID- 26139454 TI - Validation of Stroke Diagnosis in the National Registry of Hospitalized Patients in the Czech Republic. AB - BACKGROUND: Stroke is a common cause of mortality and morbidity in Eastern Europe. However, detailed epidemiological data are not available. The National Registry of Hospitalized Patients (NRHOSP) is a nationwide registry of prospectively collected data regarding each hospitalization in the Czech Republic since 1998. As a first step in the evaluation of stroke epidemiology in the Czech Republic, we validated stroke cases in NRHOSP. METHODS: Any hospital in the Czech Republic with a sufficient number of cases was included. We randomly selected 10 of all 72 hospitals and then 50 patients from each hospital in 2011 stratified according to stroke diagnosis (International Classification of Diseases Tenth Revision [ICD-10] cerebrovascular codes I60, I61, I63, I64, and G45). Discharge summaries from hospitalization were reviewed independently by 2 reviewers and compared with NRHOSP for accuracy of discharge diagnosis. Any disagreements were adjudicated by a third reviewer. RESULTS: Of 500 requested discharge summaries, 484 (97%) were available. Validators confirmed diagnosis in NRHOSP as follows: transient ischemic attack (TIA) or any stroke type in 82% (95% confidence interval [CI], 79-86), any stroke type in 85% (95% CI, 81-88), I63/cerebral infarction in 82% (95% CI, 74-89), I60/subarachnoid hemorrhage in 91% (95% CI, 85 97), I61/intracerebral hemorrhage in 91% (95% CI, 85-96), and G45/TIA in 49% (95% CI, 39-58). The most important reason for disagreement was use of I64/stroke, not specified for patients with I63. CONCLUSIONS: The accuracy of coding of the stroke ICD-10 codes for subarachnoid hemorrhage (I60) and intracerebral hemorrhage (I61) included in a Czech Republic national registry was high. The accuracy of coding for I63/cerebral infarction was somewhat lower than for ICH and SAH. PMID- 26139455 TI - Low Yield of Mobile Cardiac Outpatient Telemetry after Cryptogenic Stroke in Patients with Extensive Cardiac Imaging. AB - BACKGROUND: Detection of paroxysmal atrial fibrillation (AF) after cryptogenic stroke (CS) or transient ischemic attack ranges from 5% to 24%, but previous studies have had varying definitions of both. We aimed to evaluate the yield of up to 30 days of mobile cardiac outpatient telemetry (MCOT) for this dysrhythmia in CS patients who had undergone extensive cardiac imaging before monitoring. METHODS: We reviewed data from our center on patients with CS who completed MCOT within 3 months of the cerebrovascular event from May 2009 to January 2014; 14-30 days of monitoring was performed using one of 3 approved devices after cardiac imaging did not demonstrate a clear embolic source. We estimated the prevalence and 95% confidence intervals of AF. RESULTS: Eighty-five patients met the study criteria; 89.4% underwent transthoracic echocardiogram, 68.2% underwent transesophageal echocardiography, and 38.8% completed cardiac magnetic resonance imaging. We found 4 (4.7%, 95% confidence interval 1.5% to 11.9%) patients with AF by MCOT. There were no univariate predictors of AF. CONCLUSIONS: The diagnostic yield of cardiac rhythm monitoring for up to 30 days in CS patients may be lower than previously reported. This may be because of the routine use of cardiac imaging to identify a likely source of embolism, resulting in a lower incidence of occult AF in patients who are labeled as "cryptogenic." Longer monitoring may be needed to detect this dysrhythmia in high-risk patients who have already undergone extensive cardiac imaging. PMID- 26139456 TI - Hospital-Based Prospective Registration of Acute Transient Ischemic Attack and Noncerebrovascular Events in Korea. AB - BACKGROUND: There have been no prospective studies on the clinical features, etiologies, and outcome of transient ischemic attack (TIA) in Korea. The aim of this study was to identify variables that can discriminate TIA from TIA mimics. Also we evaluated the characteristic of TIA patients according to the presence of diffusion-weighted imaging (DWI) lesion. METHODS: Patients were categorized into TIA and TIA mimics according to the result of an initial workup. TIA patients were divided according to the presence of DWI lesions. Baseline demographics, risk factors, laboratory results, initial blood pressure, imaging findings, recurrence rate of TIA or stroke at 3 months, and initial neurologic manifestations were prospectively collected and compared. RESULTS: We evaluated a total of 252 patients (212 with TIA and 40 with TIA mimics). Steno-occlusion of the relevant artery (odds ratio [OR], 22.39; 95% confidence interval [CI], 2.03 246.73) and cardioembolic risk (OR, 32.15; 95% CI, 1.12-922.97) were significantly associated with TIA. Amnesia (OR, .001; 95% CI, .00-.05) and consciousness disturbance (OR, .003; 95% CI, .00-.06) favored TIA mimics. Perfusion defect (OR, 5.56; 95% CI, 2.90-10.68) and cardioembolic risk (OR, 2.68; 95% CI, 1.14-6.32) were significantly associated with DWI lesion. Recurrence did not significantly differ according to the presence of a lesion on DWI (positive, 4.9%; negative, 7.8%; P = .41). CONCLUSION: Steno-occlusive disease and cardioembolic risk were independently associated with TIA. Perfusion defect and cardioembolic risk predicted positive DWI lesion. The value of various imaging modalities for predicting TIA etiology needs further evaluation. PMID- 26139457 TI - Relationship between Aging and Enlargement of Intracranial Aneurysms. AB - BACKGROUND: To predict possible enlargement of cerebral aneurysms with aging, we retrospectively analyzed aneurysm size in relation to patient age and aneurysm site. METHODS: We included 1332 unruptured and 2362 ruptured aneurysms detected in patients from the Yamaguchi Prefecture, Japan, from 1995 to 2005. RESULTS: Age specific site distribution was not found in the unruptured aneurysms. In the ruptured aneurysms, the incidence of anterior communicating artery (AComA) aneurysms was higher than that of internal carotid posterior communicating (ICPC) artery aneurysms among the patients aged 40-49 years (32.6% versus 14.4%), whereas the difference was small among the elderly patients aged 70-79 years (25.8% versus 24.9%). In the AComA aneurysms, either in the unruptured or ruptured cases, no age-related change in size was found. In the ICPC aneurysms, either in the unruptured or in the ruptured cases, the size of the aneurysms 7 mm or larger increased with age. CONCLUSIONS: The sizes of AComA aneurysms may remain stable with aging. Therefore, the risk of rupture may be similar in young and elderly patients. Meanwhile, ICPC artery aneurysms may continue to grow throughout the patient's life, with an increasing risk of rupture. PMID- 26139458 TI - Urodynamic findings, bladder emptying methods and therapeutic approaches in patients with upper lumbar and lower lumbar-sacral spinal cord injury. AB - There have been previous reports of both demographic and clinical features with urodynamic evaluation results of patients with traumatic spinal cord injury (SCI). These studies were conducted on patients with cervical and thoracal SCI, but there has been no comparative study evaluating the urodynamic outcomes of patients with lumbosacral SCI. Therefore, it was aimed to investigate the bladder features and treatment options in patients with lumbosacral SCI to be able to take appropriate therapeutic decisions. The urodynamic data of 121 patients with lumbar and sacral SCI were obtained retrospectively using the urodynamics unit records. The patients were grouped as upper lumbar (L1 and L2) SCI (ULSCI) and lower lumbar-sacral (L3 to S5) SCI (LLSSCI). The patients were 92 males (76 %) and 29 (24 %) females, comprising 74 (61.2 %) ULSCI patients and 47 (38.8 %) LLSSCI patients. Detrusor hypocompliancy and anticholinergic prescription were more frequent in the ULSCI group than in the LLSSCI group, while alpha-blocker prescription was more frequent in the LLSSCI group than in the ULSCI group. There was a statistically significant difference between the groups in respect of the rates of bladder-emptying method on admission. A higher mean micturated urine volume was observed in the LLSSCI group than in the ULSCI group. The rates of bladder-filling sensation, detrusor overactivity, bladder-storage and emptying disorders, prescribed emptying method, and residual urine volume were similar in both groups. These results showed that there are differences in neurogenic bladder features and treatment options for patients with upper lumbar and lower lumbar-sacral SCI. PMID- 26139459 TI - Optimization of biostimulant for bioremediation of contaminated coastal sediment by response surface methodology (RSM) and evaluation of microbial diversity by pyrosequencing. AB - The present study aims to optimize the slow release biostimulant ball (BSB) for bioremediation of contaminated coastal sediment using response surface methodology (RSM). Different bacterial communities were evaluated using a pyrosequencing-based approach in contaminated coastal sediments. The effects of BSB size (1-5cm), distance (1-10cm) and time (1-4months) on changes in chemical oxygen demand (COD) and volatile solid (VS) reduction were determined. Maximum reductions of COD and VS, 89.7% and 78.8%, respectively, were observed at a 3cm ball size, 5.5cm distance and 4months; these values are the optimum conditions for effective treatment of contaminated coastal sediment. Most of the variance in COD and VS (0.9291 and 0.9369, respectively) was explained in our chosen models. BSB is a promising method for COD and VS reduction and enhancement of SRB diversity. PMID- 26139460 TI - Distribution and enrichment of trace metals in marine sediments from the Eastern Equatorial Atlantic, off the Coast of Ghana in the Gulf of Guinea. AB - We present results of a preliminary geochemical assessment of Cd, Pb, V, As, Ni, Cu, Zn, Mg, Al, K, Ca, and Fe in marine sediments from the Eastern Equatorial Atlantic, off the Coast of Ghana. Samples were taken along 4 regions G1, G2, G3 and G4 at approximately 25m, 100m, and 250m, 500m and 1000m depths. Elemental compositions were assessed through the estimation of Al-normalized enrichment factors and geochemical accumulation indices, and the concentrations determined to produce any potential toxic effects to biota. Significant enrichment of the bottom sediments with Cd, Ni and As were observed at some locations with sediments showing signs of heavy pollution with As at region G4. Apart from Ni, V and As which were beyond threshold effects levels at most regions, all other metals were below probable effect levels. Both natural and anthropogenic processes controlled trace metal accumulation and distribution in the Ghanaian coastal environment. PMID- 26139461 TI - "Natural course" of disease in patients with metastatic castrate-resistant prostate cancer: Survival and prognostic factors without life-prolonging treatment. AB - OBJECTIVE: The aim of this study was to determine survival and prognostic factors in unselected patients with metastatic castrate-resistant prostate cancer (mCRPC), who never received life-prolonging treatment. MATERIALS AND METHODS: The study was a retrospective analysis of a consecutive sample of patients with mCRPC seen at the urological unit of a local hospital from 2000 to 2005, their mCRPC diagnosis based on rising prostate-specific antigen (PSA) during androgen depletion treatment (ADT). RESULTS: Median overall survival was 12.3 months (range 0.2-108 months), the 3 year survival was 16.9% (95% confidence interval 0.11-0.24) and two patients were alive at the end of follow-up. Compared to a PSA nadir of greater than 11 MUg/l during ADT, a PSA nadir of less than 1 MUg/l significantly decreased the risk of death by 71%. A PSA doubling time less than 1.6 months during the early phase of mCRCP almost tripled the risk of death compared to a PSA doubling time longer than 3 months. Alkaline phosphatase serum levels and hemoglobin levels within the normal range indicated a favorable prognosis. CONCLUSIONS: The "natural course" of mCRPC varies without life prolonging treatment along with PSA nadir during ADT, PSA doubling time, alkaline phosphatase and hemoglobin level at mCRPC diagnosis. 3-year survival or longer is observed in 16.9% of patients. In clinical intervention trials among mCRPC patients, all known prognostic factors should be taken into account during the randomization process and during survival analyses. PMID- 26139462 TI - Platelet Inhibitors Reduce Rupture in a Mouse Model of Established Abdominal Aortic Aneurysm. AB - OBJECTIVE: Rupture of abdominal aortic aneurysms causes a high morbidity and mortality in the elderly population. Platelet-rich thrombi form on the surface of aneurysms and may contribute to disease progression. In this study, we used a pharmacological approach to examine a role of platelets in established aneurysms induced by angiotensin II infusion into hypercholesterolemic mice. APPROACH AND RESULTS: Administration of the platelet inhibitors aspirin or clopidogrel bisulfate to established abdominal aortic aneurysms dramatically reduced rupture. These platelet inhibitors reduced abdominal aortic platelet and macrophage recruitment resulting in decreased active matrix metalloproteinase-2 and matrix metalloproteinase-9. Platelet inhibitors also resulted in reduced plasma concentrations of platelet factor 4, cytokines, and components of the plasminogen activation system in mice. To determine the validity of these findings in human subjects, a cohort of aneurysm patients were retrospectively analyzed using developed and validated algorithms in the electronic medical record database at Vanderbilt University. Similar to mice, administration of aspirin or P2Y12 inhibitors was associated with reduced death among patients with abdominal aortic aneurysm. CONCLUSIONS: These results suggest that platelets contribute to abdominal aortic aneurysm progression and rupture. PMID- 26139463 TI - Senescent Vascular Smooth Muscle Cells Drive Inflammation Through an Interleukin 1alpha-Dependent Senescence-Associated Secretory Phenotype. AB - OBJECTIVE: Vascular smooth muscle cells (VSMCs) that become senescent are both present within atherosclerotic plaques and thought to be important to the disease process. However, senescent VSMCs are generally considered to only contribute through inaction, with failure to proliferate resulting in VSMC- and collagen poor unstable fibrous caps. Whether senescent VSMCs can actively contribute to atherogenic processes, such as inflammation, is unknown. APPROACH AND RESULTS: We find that senescent human VSMCs develop a proinflammatory state known as a senescence-associated secretory phenotype. Senescent human VSMCs release high levels of multiple cytokines and chemokines driven by secreted interleukin-1alpha acting in an autocrine manner. Consequently, the VSMC senescence-associated secretory phenotype promotes chemotaxis of mononuclear cells in vitro and in vivo. In addition, senescent VSMCs release active matrix metalloproteinase-9, secrete less collagen, upregulate multiple inflammasome components, and prime adjacent endothelial cells and VSMCs to a proadhesive and proinflammatory state. Importantly, maintaining the senescence-associated secretory phenotype places a large metabolic burden on senescent VSMCs, such that they can be selectively killed by inhibiting glucose utilization. CONCLUSIONS: Senescent VSMCs may actively contribute toward the chronic inflammation associated with atherosclerosis through the interleukin-1alpha-driven senescence-associated secretory phenotype and the priming of adjacent cells to a proatherosclerotic state. These data also suggest that inhibition of this potentially important source of chronic inflammation in atherosclerosis requires blockade of interleukin-1alpha and not interleukin-1beta. PMID- 26139465 TI - Structural activity relationship analysis (SAR) and in vitro testing reveal the anti-ageing potential activity of acetyl aspartic acid. AB - BACKGROUND: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap), aiming for identification of new compounds with anti-ageing properties. OBJECTIVE: The aim of this study was to use structural activity relationship (SAR) analysis to identify a predictive mechanism of action of A-A-A. The findings from SAR will be further characterized by in vitro activity testing. Furthermore, we aimed to investigate the role of polymerized filamentous F-actin in ageing fibroblasts and to evaluate the effect of A-A-A on this model. METHODS: To predict the mode of action of A-A-A, we used the PASS computer program as a SAR model. In vitro, scratch motility tests with immortalized keratinocytes were used as a model for wound healing potential. Matrix metalloproteinase 1-3 (MMP 1-3) was analysed using multiplex protein assays (Luminex), and polymerized actin was detected by phalloidin staining in dermal fibroblasts (HDF). RESULTS: SAR analysis predicted that A-A-A would possess both epidermal and dermal activities with identification of wound healing and MMP inhibition potential. Further in vitro studies confirmed the wound healing potential using keratinocyte scratch motility assays. We were also able to confirm the dermal activities predicted by inhibition of MMP (MMP 1 3) in HDF by A-A-A. In addition, we found a positive relationship between age and F-actin expression. We also discovered that stimulation of HDF with A-A-A for 72 h significantly reduced the polymerized cytoskeletal network as visualized by inhibition of F-actin expression. In fact, A-A-A leveraged the expression of F actin in middle-aged female fibroblasts (50 years of age) to the level of young female fibroblasts (30 years of age), corresponding to a 40% reduction in F-actin expression. CONCLUSION: Using an in silico and in vitro approach, we were able to demonstrate that A-A-A has the capacity to target different compartments of the skin through keratinocyte regeneration, MMP inhibition and relief in fibroblasts stiffness by reduction of F-actin cytoskeletal network in HDF. PMID- 26139464 TI - Proangiogenic Properties of Thrombospondin-4. AB - OBJECTIVE: Thrombospondin-4 (TSP-4) is 1 of the 5 members of the thrombospondin protein family. TSP-1 and TSP-2 are potent antiangiogenic proteins. However, angiogenic properties of the 3 other TSPs, which do not contain the domains associated with the antiangiogeneic activity of TSP-1 and TSP-2, have not been explored. In our previous studies, we found that TSP-4 is expressed in the vascular matrix of blood vessels of various sizes and is especially abundant in capillaries. We sought to identify the function of TSP-4 in the regulation of angiogenesis. APPROACH AND RESULTS: The effect of TSP-4 in in vivo angiogenesis models and its effect on angiogenesis-related properties in cultured cells were assessed using Thbs4(-/-) mice, endothelial cells (EC) derived from these mice, and recombinant TSP-4. Angiogenesis was decreased in Thbs4(-/-) mice compared with wild-type mice. TSP-4 was detected in the lumen of the growing blood vessels. Mice expressing the P387 TSP-4 variant, which was previously associated with coronary artery disease and found to be more active in its cellular interactions, displayed greater angiogenesis compared with A387 form. Lung EC from Thbs4(-/-) mice exhibited decreased adhesion, migration, and proliferation capacities compared with EC from wild-type mice. Recombinant TSP-4 promoted proliferation and the migration of EC. Integrin alpha2 and gabapentin receptor alpha2delta-1 were identified as receptors involved in regulation of EC adhesion, migration, and proliferation by TSP-4. CONCLUSION: TSP-4, an extracellular matrix protein previously associated with tissue remodeling, is now demonstrated to possess proangiogenic activity. PMID- 26139466 TI - Downregulation of RANKL and RANKL/osteoprotegerin ratio in human periodontal ligament cells during their osteogenic differentiation. AB - BACKGROUND AND OBJECTIVE: Human periodontal ligament cells (hPDLCs) are considered the promising seed cells in periodontal tissue engineering. Previous studies have discovered the ability of hPDLCs in alveolar bone formation. It remains unclear, however, how the expression of factors associated with osteoclastogenesis in hPDLCs change during their osteogenic differentiation. OBJECTIVE: The present study aimed to observe the regulation of receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) in hPDLCs during their osteogenic differentiation. MATERIAL AND METHODS: hPDLCs were treated with (M group) or without (C group) the osteogenic induction medium. Alkaline phosphatase activity was displayed with the Gomori calcium phosphate method. Mineralized nodules were detected with von Kossa staining. Expression levels of RANKL and OPG in hPDLCs were analyzed with real-time reverse transcription-polymerase chain reaction and western blot. Tartrate-resistant acid phosphatase (TRAP) staining was used to display the TRAP activity in Raw264.7 cells co-cultured with hPDLCs in the M group and the C group. RESULTS: We found that alkaline phosphatase staining was shown to be remarkably higher in the M group than that in the C group during the 21 d interval. Mineralized nodules could be seen in the M group but not in the C group. The expression levels of RANKL mRNA significantly decreased in the M group by 1.69-fold (p = 0.096) at day 7, by 2.04-fold (p = 0.000) at day 14 and by 1.84-fold (p = 0.023) at day 21, compared with the corresponding levels of RANKL in the C group. Similarly, the levels of RANKL protein decreased in the M group by 1.82-fold (p = 0.062) at day 7, by 5.64-fold (p = 0.000) at day 14 and by 4.84-fold (p = 0.000) at day 21. The mRNA and protein expression levels of OPG tended to increase in the M group. As a result, the RANKL/OPG mRNA and protein ratios were significantly downregulated by osteogenic induction. In addition, the number of TRAP staining-positive multinuclear cells in the M group was significantly less than in the C group (p = 0.018). CONCLUSION: hPDLCs may help inhibit the resorption of alveolar bone during their osteogenic differentiation by reducing the RANKL expression and the RANKL/OPG ratio. PMID- 26139467 TI - Getting to the root of epidemic spread with phylodynamic analysis of genomic data. AB - When epidemiological and evolutionary dynamics occur on similar timescales, pathogen genomes sampled from infected hosts carry a signature of the dynamics of epidemic spread. Phylodynamic inference methods aim to extract this signature from genetic data. We discuss the contribution of phylodynamics toward understanding the 2014 West African Ebola virus epidemic. PMID- 26139468 TI - Appropriateness of diagnostic effort in hospital emergency room attention for episodes of COPD exacerbation. AB - RATIONALE, AIMS AND OBJECTIVES: To assess the adequacy of diagnostic effort in the emergency departments of Spanish hospitals with respect to episodes of exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: A descriptive cross-sectional study, conducted between 2007 and 2010 in 15 hospitals in Andalusia, Catalonia, Madrid and the Basque Country. The study population included cases of COPD exacerbation attended at the emergency departments of the participating hospitals. Diagnostic efforts were considered sufficient and appropriate when the emergency room conducted a clinical evaluation including electrocardiogram, chest X-ray, arterial blood gas analysis and spirometry. RESULTS: 2852 episodes of COPD exacerbation attended in hospital emergency departments were assessed. 91.4% of the patients were male, with a mean age of 72.8 (SD 9.5) years, and 45.6% had had a previous emergency admission. The diagnostic effort was considered adequate in 60.1% of the episodes (95% CI: 58.3 61.9). The inter-hospital range of variation(25-75) was 1.67 and the coefficient of variation was 28.3%. In multivariate analysis, adjusting for hospital, date of admission and previous hospitalization, among the male patients, the OR for adequate diagnostic effort was 1.38 (95% CI: 1.04-1.84) CONCLUSION: With respect to diagnostic effort, inequities were observed in our assessment of episodes of COPD exacerbation attended in the emergency departments of Spanish public hospitals. In a high percentage of cases (40%), proper assessment was not conducted. Moreover, inter-individual and inter-hospital differences were observed. PMID- 26139469 TI - Inflammation, neurotrophism and oxidative stress and childhood psychopathology in a large community sample. AB - OBJECTIVE: To investigate the association between peripheral biomarkers and child psychopathology in a large community sample. METHOD: A total of 625 aged 6- to 13 year old subjects were recruited from a community school-based study. Psychopathology was assessed using the Child Behaviour Checklist (CBCL). Psychiatric diagnosis was evaluated using the Development and Well-Being Assessment. The following biomarkers were examined in peripheral blood: brain derived neurotrophic factor, cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-g, and TNF-alpha), chemokines (eotaxin/CCL11, IP-10, MCP-1), cytokine receptors (sTNFR1 and sTNFR2), and the oxidative stress marker TBARS. RESULTS: We found significant associations between sTNFR2, eotaxin/CCL11 and CBCL total score, as well as with specific dimensions of psychopathology. There were different patterns of association between these biomarkers and psychological and behavioural symptoms in children with and without a mental disorder. TBARS, IL-6 and MCP-1 were more specific to some clusters of symptoms in children with a psychiatric diagnosis. CONCLUSION: Our data support the potential use of biomarkers, especially those involved in immune-inflammatory pathways, in investigating neurodevelopmental psychopathology. Their association with different dimensions of symptoms might be of useful when analyzing illness severity and clusters of symptoms within specific disorders. PMID- 26139470 TI - Structural colour in Chondrus crispus. AB - The marine world is incredibly rich in brilliant and intense colours. Photonic structures are found in many different species and provide extremely complex optical responses that cannot be achieved solely by pigments. In this study we examine the cuticular structure of the red alga Chondrus crispus (Irish Moss) using anatomical and optical approaches. We experimentally measure the optical response of the multilayer structure in the cuticle. Using finite-difference time domain modelling, we demonstrate conclusively for the first time that the dimensions and organisation of lamellae are responsible for the blue structural colouration on the surface of the fronds. Comparison of material along the apical basal axis of the frond demonstrates that structural colour is confined to the tips of the thalli and show definitively that a lack of structural colour elsewhere corresponds with a reduction in the number of lamellae and the regularity of their ordering. Moreover, by studying the optical response for different hydration conditions, we demonstrate that the cuticular structure is highly porous and that the presence of water plays a critical role in its ability to act as a structural light reflector. PMID- 26139471 TI - Blockade of CD82 by a monoclonal antibody potentiates anti-leukemia effects of AraC in vivo. AB - We recently found that CD82 inhibits matrix metalloproteinase 9 and augments adhesion of CD34(+) /CD38(-) acute myelogenous leukemia (AML) cells to the bone marrow (BM) microenvironment. The present study found that the use of an anti CD82 monoclonal antibody (CD82 mAb) mobilized CD34(+) leukemia cells from BM into the peripheral blood in a humanized AML murine model. The use of CD82 mAb in combination with cytarabine (AraC) significantly prolonged survival of immunodeficient mice-bearing human AML cells than did treatment with either AraC or CD82 mAb alone. Taken together, the combination of an anti-leukemic agent and the mobilizing agent CD82 mAb may be a promising treatment strategy to treat patients with AML. PMID- 26139472 TI - Ultrasound-assisted three-phase partitioning of polyphenol oxidase from potato peel (Solanum tuberosum). AB - Conventional three phase partitioning (TPP) and ultrasound assisted three phase partitioning (UATPP) were optimized for achieving the maximum extraction and purification of polyphenol oxidase (PPO) from waste potato peels. Different process parameters such as ammonium sulfate (NH4)2SO4 concentration, crude extract to t-butanol ratio, time, temperature and pH were studied for conventional TPP. Except agitation speed, the similar parameters were also optimized for UATPP. Further additional parameters were also studied for UATPP viz. irradiation time at different frequencies, duty cycle and, rated power in order to obtain the maximum purification factor and recovery of PPO. The optimized conditions for conventional TPP were (NH4)2SO4 0-40% (w/v), extract to t-butanol ratio 1:1 (v/v), time 40 min and pH 7 at 30 degrees C. These conditions provided 6.3 purification factor and 70% recovery of PPO from bottom phase. On the other hand, UATPP gives maximum purification fold of 19.7 with 98.3% recovery under optimized parameters which includes (NH4)2SO4 0-40% (w/v), crude extract to t-butanol ratio 1: 1 (v/v) pH 7, irradiation time 5 min with 25 kHz, duty cycle 40% and rated power 150W at 30 degrees C. UATPP delivers higher purification factor and % recovery of PPO along with reduced operation time from 40 min to 5 min when compared with TPP. SDS PAGE showed partial purification of PPO enzyme with UATPP with molecular weight in the range of 26-36 kDa. Results reveal that UATPP would be an attractive option for the isolation and purification of PPO without need of multiple steps. PMID- 26139473 TI - The Three-Dimensional Morphology of Growing Dendrites. AB - The processes controlling the morphology of dendrites have been of great interest to a wide range of communities, since they are examples of an out-of-equilibrium pattern forming system, there is a clear connection with battery failure processes, and their morphology sets the properties of many metallic alloys. We determine the three-dimensional morphology of free growing metallic dendrites using a novel X-ray tomographic technique that improves the temporal resolution by more than an order of magnitude compared to conventional techniques. These measurements show that the growth morphology of metallic dendrites is surprisingly different from that seen in model systems, the morphology is not self-similar with distance back from the tip, and that this morphology can have an unexpectedly strong influence on solute segregation in castings. These experiments also provide benchmark data that can be used to validate simulations of free dendritic growth. PMID- 26139474 TI - Brain size as a driver of avian escape strategy. AB - After detecting an approaching predator, animals make a decision when to flee. Prey will initiate flight soon after detecting a predator so as to minimize attentional costs related to on-going monitoring of the whereabouts of the predator. Such costs may compete with foraging and other maintenance activities and hence be larger than the costs of immediate flight. The drivers of interspecific variation in escape strategy are poorly known. Here we investigated the morphological, life history and natural history traits that correlate with variation in avian escape strategy across a sample of 96 species of birds. Brain mass, body size, habitat structure and group size were the main predictors of escape strategy. The direction of the effect of these traits was consistent with selection for a reduction of monitoring costs. Therefore, attentional costs depend on relative brain size, which determines the ability to monitor the whereabouts of potential predators and the difficulty of this task as reflected by habitat and social complexity. Thus brain size, and the cognitive functions associated with it, constitute a general framework for explaining the effects of body size, habitat structure and sociality identified as determinants of avian escape strategy. PMID- 26139475 TI - Atopy and Asthma in Migrants: The Function of Parasites. AB - Migration studies have shown that environmental factors in more developed and industrialized countries facilitate atopy and asthma in a time-dependent manner and are affected by age at immigration. Levels of immunoglobulin E are higher in immigrants than in the local population and gradually decrease to the levels of the general population. Parasitic infestation may function in the prevention and pathogenesis of atopic conditions in immigrants from developing countries. Helminths are associated with a reduced prevalence of clinically important atopic disorders, likely because of induction of a regulatory cell population mechanism. Improved understanding of the immunologic background of helminths and their protective function in humans has led to a growing interest in the possibility of reversal of allergies using parasites and the development of new therapies, such as immunomodulation for allergy using ova from parasites orally or intranasally. Strategies for primary prevention in high-risk atopic individuals and secondary prevention guidelines should be developed for populations in developing countries and for immigrants from developing countries to atopy-prevalent developed countries. Improved understanding of the function of parasitic infection in modulation of the immune response may lead to new therapeutic options for allergic conditions. PMID- 26139476 TI - Downloading plug-ins for nationalism and cosmopolitanism. AB - A crucial factor in differentiation between existing approaches to nationalism and cosmopolitanism is the positioning of these approaches within a continuum between particularism and universalism, based on their understanding of space and time. However, this also poses a major difficulty in studying practices of nationalism and cosmopolitanism: Reducing these practices to a position within the particularism/universalism continuum establishes different forms of nationalism and cosmopolitanism as 'order of things', through which any practice is projected as an approximation or a distortion of this ideal 'order'. Such a projection tells more about the researchers' own theoretical commitments than the participants' practices. This article utilizes some conceptual tools from Actor Network Theory in an effort to establish a sketch for an alternative projection to study practices of nationalism and cosmopolitanism, which will give the participants an opportunity to perform their own time and space, instead of reducing them to placeholders of an already determined position, a priori identified by researchers. PMID- 26139477 TI - Rehmannia glutinosa reduced waist circumferences of Korean obese women possibly through modulation of gut microbiota. AB - The clinical study reported here was conducted in order to analyze the anti obesity effect of the steamed root of Rehmannia glutinosa Libosch (Shu Dihuang), a Chinese herbal medicine widely used for the treatment of metabolic diseases. To understand the mechanism(s) underlying the beneficial effects of R. glutinosa, we investigated the changes in gut microbiota after herbal intervention through 16S rRNA gene-based pyrosequencing analyses. Twelve female middle-aged subjects (40 65 years old) with body mass index (BMI) over 25 kg m(-2) were included in this study which involved intake of steamed roots of R. glutinosa for eight weeks. The subjects were visited for anthropometric measurements every two weeks and fecal samples were collected before and after the intervention. All subjects showed a significantly decreased waist circumference following the herbal treatment. The relative abundances of fecal microbiota suggested an association of intake of R. glutinosa with increases in phylum Actinobacteria and genus Bifidobacterium, while phylum Firmicutes and genus Blautia were decreased in response to the herbal treatment. Based on these findings, it is conceivable that a decrease in the waist circumferences after R. glutinosa intake may be related to alteration of intestinal microbiota and the herbal intervention has the potential as a prebiotic. PMID- 26139478 TI - From CT scanning to 3-D printing technology for the preoperative planning in laparoscopic splenectomy. AB - BACKGROUND: Three-dimensional printing technology is rapidly changing the way we produce all sort of objects, having also included medical applications. We embarked in a pilot study to assess the value of patient-specific 3-D physical manufacturing of spleno-pancreatic anatomy in helping during patient's counseling and for preoperative planning. METHODS: Twelve patients scheduled for a laparoscopic splenectomy underwent contrast CT and subsequent post-processing to create virtual 3-D models of the target anatomy, and 3-D printing of the relative solid objects. The printing process, its cost and encountered problems were monitored and recorded. Patients were asked to rate the value of 3-D objects on a 1-5 scale in facilitating their understanding of the proposed procedure. Also 10 surgical residents were required to evaluate the perceived extra value of 3-D printing in the preoperative planning process. RESULTS: The post-processing analysis required an average of 2; 20 h was needed to physically print each model and 4 additional hours to finalize each object. The cost for the material employed for each object was around 300 euros. Ten patients gave a score of 5, two a score of 4. Six residents gave a score of 5, four a score of 4. CONCLUSIONS: Three-dimensional printing is helpful in understanding complex anatomy for educational purposes at all levels. Cost and working time to produce good quality objects are still considerable. PMID- 26139479 TI - Timing of percutaneous cholecystostomy affects conversion rate of delayed laparoscopic cholecystectomy for severe acute cholecystitis. AB - BACKGROUND: Percutaneous cholecystostomy is reserved for very high-operative-risk patients suffering from severe acute cholecystitis, who do not respond to conservative treatment. It is associated with high conversion rate to open surgery, when cholecystectomy is held later on. Our objective was to assess whether early timing of percutaneous cholecystostomy decreases conversion rate of delayed laparoscopic cholecystectomy to open surgery. METHODS: The study population included 59 patients who underwent percutaneous cholecystostomy for severe cholecystitis and then proceeded to delayed interval laparoscopic cholecystectomy. The study consisted of a retrospective survey of medical files, based on a prospective enrollment of the data. We assessed conversion rate between two groups based on the time period from onset of symptoms and from admission to hospital until performance of cholecystostomy. RESULTS: Regarding the time from onset of pain to drainage, early cholecystostomy (within 2 days, group I) was associated with 8.3% conversion rate, in contrast to 33.3% in group II (3-6 days from onset of symptoms). Regarding the day of admission to hospital, early drainage revealed 16% conversion rate in contrast to 40.7% in later drainage (p = 0.047, Chi-square test). We found correlation between time interval of symptoms and admission to conversion rate, according to Spearman's correlation coefficient. CONCLUSIONS: Early percutaneous cholecystostomy does decrease conversion rate of delayed laparoscopic cholecystectomy, possibly by halting the propagation of the inflammatory process and its consequences. When decision regarding the necessity to perform drainage of the severely inflamed gallbladder is established, it is suggested to be done as soon as possible. PMID- 26139481 TI - Validity evidence for a new portable, lower-cost platform for the fundamentals of endoscopic surgery skills test. AB - BACKGROUND: The fundamentals of endoscopic surgery (FES) examination measures the knowledge and skills required to perform safe flexible endoscopy. A potential limitation of the FES skills test is the size and cost of the simulator on which it was developed (GI Mentor II virtual reality endoscopy simulator; Simbionix LTD, Israel). A more compact and lower-cost alternative (GI Mentor Express) was developed to address this issue. The purpose of this study was to obtain evidence for the validity of scores obtained on the Express platform, so that it can be used for testing. STUDY DESIGN: General surgery residents at various levels of training and practicing endoscopists at five institutions participated. Each completed the five FES tasks on both simulator platforms in random order, with 3 14 days between tests. Scores were calculated using the same standardized computer-generated algorithm and compared using Pearson's correlation coefficient. RESULTS: There were 58 participants (mean age 32; 76% male) with a broad range of endoscopic experience. The mean (95% confidence interval) FES scores were 72 (67:77) on the GI Mentor II and 66 (60:71) on the Express. The correlation between scores on the two platforms was 0.86 (0.77:0.91; p < 0.0001). CONCLUSION: There is a high correlation between FES manual skills scores measured on the original platform and the new Express, providing evidence to support the use of the GI Mentor Express for FES testing. PMID- 26139482 TI - Techniques to perform a laparoscopic right adrenalectomy for metastases abutting the liver, renal vein, and posterior vena cava. AB - INTRODUCTION: Introduction Laparoscopic adrenalectomy (LA) may be associated with reduction in postoperative pain, morbidity, length of stay, and cost compared to open adrenalectomy, and, as a result, has become a preferred approach for benign tumors. Though recent series have reported safety and oncologic non-inferiority with a minimally invasive approach to malignant and metastatic adrenal tumors, relative contraindications to LA include malignancy, large size, and invasion or abutment of vital structures. METHODS/RESULTS: We demonstrate techniques to perform LA in an obese patient with a large ([6 cm) solitary breast metastasis to the right adrenal gland that was adherent to the liver, inferior vena cava (IVC), and right renal vein. The tumor was growing behind the infrahepatic IVC and was abutting the confluence of the renal vein/IVC. The patient was monitored on systemic treatment with no new sites of disease and after achieving a maximal response to neoadjuvant treatment. Laparoscopic techniques to safely approach adrenal tumors adherent to the liver, IVC, and renal vein are stepwise demonstrated, including appropriate patient positioning and port site selection. The tumor was excised with negative margins, and the patient was discharged on postoperative day 1 with minimal pain medication and tolerating a regular diet. CONCLUSION: Though malignancy is a relative contraindication to LA, even large right-sided adrenal tumors abutting the liver and growing behind the IVC can be safely approached while adhering to oncologic principles, as is demonstrated in this video. PMID- 26139483 TI - Natural orifice transluminal endoscopic surgery-assisted versus laparoscopic ovarian cystectomy (NAOC vs. LOC): a case-matched study. AB - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has shown its prospection as a minimally invasive endoscopic surgery. This study aimed to examine the safety and efficacy of combined NOTES and vaginal approach, natural orifice transluminal endoscopic surgery-assisted ovarian cystectomy (NAOC), in the conservative management of benign ovarian tumors. METHODS: Records were reviewed for the 34 consecutive NAOC procedures between May 2011 and March 2014. Age, body mass index, parity, size of the mass, and bilaterality of the mass were used to select comparable patient who had undergone laparoscopic ovarian cystectomy (LOC). RESULTS: A total of 277 patients were recruited in this study (243 LOCs and 34 NAOCs, respectively). There was no incidence of switching to abdominal laparotomy. Length of operation and length of postoperative stay were significantly greater in the LOC group than in the NAOC group, but total hospital charges were similar in both groups. There was no difference in febrile morbidity between the two groups but more estimated blood loss (EBL) in NAOC group, although EBL was <50 mL in the two groups. Linear correlations of mass size with operating time and EBL existed in LOC group, but not in NAOC group. CONCLUSION: NAOC can be safely performed for benign and large ovarian tumors. Besides, NAOC offers a superior operative efficiency compared with LOC. PMID- 26139484 TI - Professionalism of surgery. PMID- 26139480 TI - Laparoscopic ventral/incisional hernia repair: updated Consensus Development Conference based guidelines [corrected]. AB - BACKGROUND: The Executive board of the Italian Society for Endoscopic Surgery (SICE) promoted an update of the first evidence-based Italian Consensus Conference Guidelines 2010 because a large amount of literature has been published in the last 4 years about the topics examined and new relevant issues. METHODS: The scientific committee selected the topics to be addressed: indications to surgical treatment including special conditions (obesity, cirrhosis, diastasis recti abdominis, acute presentation); safety and outcome of intraperitoneal meshes (synthetic and biologic); fixing devices (absorbable/non absorbable); abdominal border and parastomal hernia; intraoperative and perioperative complications; and recurrent ventral/incisional hernia. All the recommendations are the result of a careful and complete literature review examined with autonomous judgment by the entire panel. The process was supervised by experts in methodology and epidemiology from the most qualified Italian institution. Two external reviewers were designed by the EAES and EHS to guarantee the most objective, transparent, and reliable work. The Oxford hierarchy (OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence") was used by the panel to grade clinical outcomes according to levels of evidence. The recommendations were based on the grading system suggested by the GRADE working group. RESULTS AND CONCLUSIONS: The availability of recent level 1 evidence (a meta-analysis of 10 RCTs) allowed to recommend that not only laparoscopic repair is an acceptable alternative to the open repair, but also it is advantageous in terms of shorter hospital stay and wound infection rate. This conclusion appears to be extremely relevant in a clinical setting. Indications about specific conditions could also be issued: laparoscopy is recommended for the treatment of recurrent ventral hernias and obese patients, while it is a potential option for compensated cirrhotic and childbearing-age female patients. Many relevant and controversial topics were thoroughly examined by this consensus conference for the first time. Among them are the issue of safety of the intraperitoneal mesh placement, traditionally considered a major drawback of the laparoscopic technique, the role for the biologic meshes, and various aspects of the laparoscopic approach for particular locations of the defect such as the abdominal border or parastomal hernias. PMID- 26139485 TI - Endoscopic repair of primary versus recurrent male unilateral inguinal hernias: Are there differences in the outcome? AB - INTRODUCTION: To date, there are no prospective randomized studies that compare the outcome of endoscopic repair of primary versus recurrent inguinal hernias. It is therefore now attempted to answer that key question on the basis of registry data. PATIENTS AND METHODS: In total, 20,624 patients were enrolled between September 1, 2009, and April 31, 2013. Of these patients, 18,142 (88.0%) had a primary and 2482 (12.0%) had a recurrent endoscopic repair. Only patients with male unilateral inguinal hernia and with a 1-year follow-up were included. The dependent variables were intra- and postoperative complications, reoperations, recurrence, and chronic pain rates. The results of unadjusted analyses were verified via multivariable analyses. RESULTS: Unadjusted analysis did not reveal any significant differences in the intraoperative complications (1.28 vs 1.33%; p = 0.849); however, there were significant differences in the postoperative complications (3.20 vs 4.03%; p = 0.036), the reoperation rate due to complications (0.84 vs 1.33%; p = 0.023), pain at rest (4.08 vs 6.16%; p < 0.001), pain on exertion (8.03 vs 11.44%; p < 0.001), chronic pain requiring treatment (2.31 vs 3.83%; p < 0.001), and the recurrence rates (0.94 vs 1.45%; p = 0.0023). Multivariable analysis confirmed the significant impact of endoscopic repair of recurrent hernia on the outcome. CONCLUSION: Comparison of perioperative and 1-year outcome for endoscopic repair of primary versus recurrent male unilateral inguinal hernia showed significant differences to the disadvantage of the recurrent operation. Therefore, endoscopic repair of recurrent inguinal hernias calls for particular competence on the part of the hernia surgeon. PMID- 26139486 TI - Long-term knowledge retention following simulation-based training for electrosurgical safety: 1-year follow-up of a randomized controlled trial. AB - BACKGROUND: Despite the value of simulation for surgical training, it is unclear whether acquired competencies persist long term. A prior randomized trial showed that structured simulation improves knowledge of the safe use of electrosurgery (ES) amongst trainees up to 3 months after the curriculum (Madani et al. in Surg Endosc 28(10):2772-2782, 2014). We now analyse long-term knowledge retention. This study estimates the effects of a structured simulation-based curriculum to teach the safe use of ES on knowledge after 1 year. METHODS: Trainees previously participated in a 1-h didactic ES course, followed by randomization into one of two groups: an unstructured hands-on session where trainees used ES devices (control group) or a goal-directed hands-on training session (Sim group). Knowledge of pre- and post-curriculum (immediate, 3 months and 1 year) and knowledge of ES safety were assessed using different multiple-choice examinations. Data are expressed as median (interquartile range), *p < 0.05. RESULTS: Fifty-nine trainees participated (30 control group; 29 Sim group). Despite equal baseline examination scores, Sim group demonstrated higher scores compared to control immediately (89% [83; 94] vs. 83% [71; 86]*), 3 months (77% [69; 90] vs. 60% [51; 80]*) and 1 year after curriculum (70% [61; 74] vs. 60% [31; 71]*). One-year score remained significantly greater compared to baseline in the Sim group (70% [61; 74] vs. 49% [43; 57]*), but was similar to baseline in the control group (60% [31; 71] vs. 45% [34; 52]). CONCLUSIONS: After ES simulation training, retention of competencies persists longer when the hands-on component is designed to reinforce specific learning objectives in a structured curriculum. Despite routine clinical use of ES devices, knowledge degrades overtime, suggesting the need for ongoing formal educational activities to reinforce curricular objectives. PMID- 26139487 TI - Early laparoscopic cholecystectomy is superior to delayed acute cholecystitis: a meta-analysis of case-control studies. AB - BACKGROUND: Since the advent of laparoscopic cholecystectomy (LC) there has been continued debate regarding the management of acute cholecystitis with either early or delayed LC. Nearly all studies have demonstrated that early LC has a significantly shorter total length of hospital stay compared with delayed LC. Although previous randomized controlled trials and meta-analysis have shown clinical outcomes to favour early surgery, clinical practice continues to vary significantly worldwide. In addition, there is much confusion in the optimal timing for early LC with definitions of early varying from 72 h to 7 days. There have been numerous case-control studies investigating the timing of LC in acute cholecystitis. The aim of this paper is to pool the results from all case-control studies to investigate outcomes including mortality rates, complication rates, length of hospital stay and conversion rates to open procedures. METHODS: A search of electronic databases was performed for case-control studies published between 1985-February 2015. RESULTS: Results from 77 case-control studies showed statistically significant reductions in mortality, complications, bile duct leaks, bile duct injuries, wound infections, conversion rates, length of hospital stay and blood loss associated with early LC. Although LC within the 72-h window is optimal, patients operated after this window still benefit from early surgery compared to delayed surgery. The duration of symptoms in acute cholecystitis should not influence the surgeons' willingness to operate acutely. CONCLUSIONS: Early LC is clearly superior to delayed LC in acute cholecystitis. The most recent evidence-based practice strongly suggests that early LC should be standard of care in the management of acute cholecystitis. PMID- 26139488 TI - Transanal minimally invasive surgery: impact on quality of life and functional outcome. AB - BACKGROUND: Transanal minimally invasive surgery (TAMIS) is emerging as an alternative to transanal endoscopic microsurgery. Quality of life (QOL) and functional outcome are important aspects when valuing a new technique. The aim of this prospective study was to assess both functional outcome and QOL after TAMIS. METHODS: From 2011 to 2013, patients were prospectively studied prior to and at least 6 months after TAMIS for rectal adenomas and low-risk T1 carcinomas using a single-site laparoscopy port. Functional outcome was determined using the Faecal Incontinence Severity Index (FISI). Quality of life was measured using functional [Faecal Incontinence Quality of Life (FIQL)] and generic (EuroQol EQ-5D) questionnaires. RESULTS: The study population consisted of 24 patients 13 men, median age 59 (range 42-83) with 24 tumours [median distance from the dentate line 8 cm (range 2-17 cm); median tumour size 6 cm(2) (range 0.25-51 cm(2)); 20 adenomas; 4 low-risk T1 carcinomas]. Post-operative complications occurred in one patient (4 %; grade IIIb according to Clavien Dindo classification). Compared to baseline, FISI remained unaffected (9.8 vs 7.3; P = 0.26), FIQL remained unaffected, and EuroQol EQ-5D improved (EQ-VAS: 77 vs 83; P = 0.04). CONCLUSION: There was no detrimental effect of TAMIS on anorectal function. Overall QOL was improved after TAMIS, probably due to removal of the tumour, and at 6 months was equal to the general population. PMID- 26139489 TI - Robotic approaches may offer benefit in colorectal procedures, more controversial in other areas: a review of 168,248 cases. AB - INTRODUCTION: While the penetrance of robotic surgery into field of urology and gynecology has been significant, general surgeons have been slower adopters. We sought to compare laparoscopy and RAS among five different general surgical procedures with various penetrance of MIS. METHODS: Following IRB approval, the New York Statewide Planning and Research Cooperative System administrative data were used to identify five common laparoscopic general surgery procedures: cholecystectomy, colectomy, esophageal fundoplication (EF), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) between 2008 and 2012. ICD-9 codes were used to select laparoscopic versus robotic procedures. Procedures were compared based on any complication and hospital length of stay (HLOS). Following descriptive analysis, propensity score analysis was used to estimate the population average differences between patients who underwent robotic-assisted and laparoscopic procedures. RESULTS: There were 1458 patients who had undergone robotic-assisted surgery and 166,790 patients who had undergone laparoscopic surgery among the five procedures between 2008 and 2012. Of the 1458 robotic cases, 186 were cholecystectomy, 307 were RYGB, 118 were SG, 288 were EF, and 559 were colectomy. Initial univariate analysis showed a significantly higher rate of overall complications and HLOS in the laparoscopic group compared to the robotic assisted group. Laparoscopic colectomy had a significantly higher rate of complications and longer length of stay compared to robotic approaches. No difference in complications or HLOS was seen in the cholecystectomy group. Following propensity score analysis, patients who had undergone robotic-assisted colectomy had significantly lower rate of complications compared to those who underwent conventional laparoscopic procedure (p value = 0.0022). In addition, patients who underwent robotic-assisted SG had on average 1.22 days longer HLOS (p value = 0.0037). CONCLUSION: Robotic approaches may facilitate safer adoption of minimally invasive approaches in areas where penetrance of conventional laparoscopy is low, such as in colorectal surgery. PMID- 26139490 TI - Nationwide variation in outcomes and cost of laparoscopic procedures. AB - INTRODUCTION: Healthcare systems and surgeons are under increasing pressure to provide high-quality care for the lowest possible cost . This study utilizes national data to examine the outcomes and costs of common laparoscopic procedures based on hospital type and location. METHODS: The National Inpatient Sample was queried from 2008 to 2011 for five laparoscopic procedures: colectomy (LC), inguinal hernia repair, ventral hernia repair (LVHR), Nissen fundoplication (NF), and cholecystectomy (LCh). Outcomes, including complication rate and inpatient mortality, were stratified by region and hospital type. Both univariate and multivariate regression analyses were performed using regression-based survey methods; risk-adjusted mean costs for hospital were calculated after adjusting for patient characteristics. RESULTS: In univariate analysis, the rates of minor complications varied significantly between geographic regions for LCh, LC, NF, and LVHR (p < 0.05). Though LCh and LVHR had statistical variation between regions for rates of major complications (p < 0.05), all regions were equivalent in rates of inpatient mortality for the procedures (p > 0.05). Rural and urban centers had similar rates of complications (p > 0.05), except for higher rates of major complications following IHR and LC in rural centers (p < 0.02) and following Nissen fundoplication in urban facilities(p < 0.0003). Though urban centers were more expensive for all procedures (p < 0.0001), mortality was similar between groups (p > 0.05). For hospital ownership, private investor-owned facilities were substantially more expensive (p < 0.0001), but had no significant differences in complications compared to other hospital types (p > 0.05). In multivariate analysis, while patient factors helped explain differences between outcome differences in different hospital types and locations, in general, the difference in cost remained statistically significant between hospitals. CONCLUSION: Though patient demographics and characteristics accounted for some differences in postoperative outcomes after common laparoscopic procedures, higher cost of care was not associated with better outcomes or more complex patients. PMID- 26139491 TI - Comparison of two different concepts of mesh and fixation technique in laparoscopic ventral hernia repair: a randomized controlled trial. AB - BACKGROUND: Patients' need to improve outcomes and to reduce the number of complications triggers the development of new materials and surgery concepts. Currently, there are many implants and fixation systems dedicated for intraperitoneal onlay mesh procedure. The aim of this study was to compare two different mesh/fixation system concepts (PH: Physiomesh/Securestrap and VS: Ventralight ST/SorbaFix) for laparoscopic ventral hernia repair with respect to pain. METHODS: A single-center, prospective, randomized study was designed to include 50 patients per group with a planned interim analysis for safety after 25 patients. The endpoints were pain occurrences and intensity, which was measured with the visual analogue scale 7 days, 30 days, 3 months and 6 months after surgery. The safety parameters included the number of recurrences and postoperative complications. RESULTS: During the interim analysis, the study was stopped due to safety reasons. We observed five (20 %) recurrences in the PH group in first 6 months and none in the VS group. We observed a significantly higher pain rate in the PH group after 3 months (p < 0.0001) and no difference after 7 days (p = 0. 7019). The pain intensity decreased significantly over time (p < 0.0001) and was significantly higher in the PH group (p < 0.0001). CONCLUSIONS: Although this clinical trial was terminated prior to the preplanned recruitment goal, the obtained results from the enrolled patients indicate that the PH system associated with significantly greater hernia recurrences and postoperative pain compared with the VS system. This confirms the superiority of the elastic mesh concept, which may be a safer and more efficacious option for laparoscopic ventral hernia repairs. PMID- 26139492 TI - Role of laparoscopic ultrasound during diagnostic laparoscopy for proximal biliary cancers: a single series of 100 patients. AB - BACKGROUND: Despite extensive preoperative evaluation, a significant proportion of patients with biliary cancer (BC) proves to be unresectable at laparotomy. Diagnostic laparoscopy (DL) has been suggested to avoid unnecessary laparotomy. Aim of the study was to evaluate the additional benefit of combining LUS to DL in patients with proximal BC. METHODS: Inclusion criteria were all patients affected by proximal BC undergone DL + LUS based on the following criteria: preoperative diagnosis of gallbladder cancer, hilar cholangiocarcinomas (HC) and borderline resectable intrahepatic cholangiocarcinoma (IHC). The overall yield (OY) and accuracy (AC) of DL +/- LUS in determining unresectable disease were calculated. RESULTS: From 01/2006 to 12/2014, 107 out of 191 (56%) potentially resectable proximal BC were evaluated. One hundred patients fulfilled inclusion criteria: 44 IHC, 21 GC and 35 HC. Forty-eight (48%) patients were male with median age of 65 (41-87) years. The median number of preoperative imaging was 3 +/- 0.99. Patients underwent DL + LUS 10.5 +/- 15.6 days after last imaging. DL + LUS identified unresectable diseases in 24 patients, 6 (25%) of them only thanks to LUS findings (3 GC and 3 IHC). At laparotomy, 6 (4 HC and 2 GC) out of 76 patients were found unresectable because of carcinomatosis (n = 2), new liver metastasis (n = 2) and vascular invasion (n = 2). LUS increased the OY (from 18 to 24%) and AC (from 60 to 80%) in the whole group. The advantages of LUS were confirmed for GC (OY from 38.1 to 52.4%, AC from 61.5 to 84.6%) and IHC patients (OY from 11.4 to 18.2%, AC from 62.5 to 100%) but not for HC group. The presence of biliary drainage was the only factor able to predict negative yield (p < 0.001). CONCLUSIONS: LUS increases overall yield and accuracy of DL for detecting unresectable disease in patients with preoperative diagnosis of gallbladder cancer and borderline resectable intrahepatic cholangiocarcinomas. PMID- 26139493 TI - Clinical outcomes of re-stenting in patients with stent malfunction in malignant gastric outlet obstruction. AB - BACKGROUND AND AIMS: Self-expanding metal stents (SEMS) have been used for the palliative treatment of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the clinical outcomes of salvage SEMS for stent malfunction and to identify the prognostic factors for a longer patency. METHODS: A total of 108 patients who underwent a secondary salvage SEMS placement for a primary stent malfunction were retrospectively reviewed at the Seoul National University Hospital between August 2004 and May 2013. The duration of patency for salvage SEMS was defined as the time between salvage SEMS placement and the recurrence of obstructive symptoms that were confirmed either endoscopically or radiologically. RESULTS: The technical and clinical success rates for salvage SEMS were 100 and 82.4% (95% confidence interval [CI] 74.0-89.0), respectively. A salvage SEMS malfunction occurred in 29 (26.9%) of the 108 patients. The median duration of patency for salvage SEMS was 59.5 days (range 3-928, 95% CI 73.7 118.3). Longer SEMS patencies of more than 60 days were significantly associated with palliative chemotherapy (odds ratio = 2.539, 95% CI 1.031-6.252, p = .043). For salvage SEMS, covered-uncovered stents had a longer patency duration, as compared with other combinations of primary and salvage stent types. CONCLUSIONS: Longer patency durations for salvage SEMS were associated with palliative chemotherapy after salvage SEMS insertion. Salvage SEMS could be a feasible and effective treatment for primary stent malfunction in malignant GOO. PMID- 26139494 TI - Endoscopic ultrasound (EUS)-guided coil injection therapy of esophagogastric and ectopic varices. AB - BACKGROUND: Endoscopic band ligation and glue injection are established techniques for variceal bleeding. As EUS may enhance variceal detection and improve therapeutic targeting, we aim to report our experience on EUS-guided coil embolization, with and without concomitant glue injection, of varices. METHODS: A prospectively maintained EUS database was retrospectively reviewed to identify consecutive patients who underwent EUS-guided variceal angiotherapy. All patients had failed or were poor candidates for standard endoscopic, surgical, or interventional radiologic therapies. The main outcome measurements were rates of rebleeding and adverse events. RESULTS: Fourteen patients [mean age 58 (SD 12) years, 50% male] underwent EUS-guided coil injection with (n = 4) or without (n = 10) concomitant glue injection to treat esophagogastric (n = 1), gastric (n = 5), duodenal (n = 3), or choledochal (n = 5) varices. Prior endoscopic and cross sectional imaging detected only 57 and 64% of the varices seen. A mean of 5.1 (SD 1.9) coils and a median of 3.25 (range 2-3.5) mL of cyanoacrylate were injected during the initial procedure. During median follow-up of 12 (range 1-104) months, three patients died from unrelated causes and eight patients did not have further bleeding episodes. In the remaining three patients who had choledochal varices, the frequency and intensity of rebleeding decreased significantly. Only one asymptomatic adverse event occurred with coil migration to the liver. CONCLUSIONS: EUS-guided angiotherapy of varices is safe and feasible in selected patients who failed conventional therapy, and should be considered in the clinical management of these patients. PMID- 26139495 TI - Preliminary evaluation of the SimPORTAL major vessel injury (MVI) repair model. AB - BACKGROUND: Major vessel injury (MVI) is a dangerous complication associated with laparoscopic surgery that leads, if not properly handled, to blood loss, conversion to open surgery, and eventually death. In this paper, we describe the preliminary evaluation of the SimPORTAL MVI model, created with the goal of simulating an intra-corporeal injury to a large vessel. METHODS: For this study, we created MVI models for 17 residents (PGY 1-4). Each resident was asked to perform an intracorporeal knot on a penrose drain within a maximum time limit of 6 min (in accordance with European basic laparoscopic urological skills rules) and then to subsequently repair a vessel injury on the MVI model, which was perfused with synthetic blood, within a maximum blood loss of 3 L. During the vessel repair, low lights and pulse sounds were used to simulate the operating room environment. All participants filled out a survey pre- and post-task to score various aspects of the model. RESULTS: We successfully created a model that simulates a critical surgical event. None of the participants reported having previous experience repairing a MVI. Six participants were able to perform the intracorporeal knot, and 12 residents (70.5%) were able to repair the MVI model under the given time and blood loss limits. Eleven participants agreed that the MVI model behaves like a real vessel, and six felt to be capable of performing the task prior to attempting it. Sixteen participants thought that the MVI model should be part of laparoscopic curriculums during residency. CONCLUSIONS: The SimPORTAL MVI model is a feasible low-cost model that would be well appreciated as a part of laparoscopic curriculum for residents. Minor improvements, including pressure measurement in the vessel for task assessment, will be made in the future, and further studies are necessary to definitively validate this model. PMID- 26139496 TI - Are there differences between right and left colectomies when performed by laparoscopy? AB - BACKGROUND: There is an extended belief that the laparoscopic approach to left colectomy (LC) is technically more demanding and associated with more postoperative complications than to right colectomy (RC). However, there is no consensus in the literature about whether the short-term outcomes of RC differ from those of LC. The aim of this paper was to compare the postoperative course of patients undergoing RC and LC. METHODS: We retrospectively analyzed 1000 consecutive patients who underwent a laparoscopic RC or LC between 1998 and 2012. Factors analyzed were intraoperative complications, surgical time, postoperative complications, and length of stay. The two groups were divided into four subgroups (neoplasia, diverticular disease, polyps, and others). RESULTS: LC was associated with more postoperative complications than RC and longer operative time both in the two main groups (postoperative complications 30 vs. 19%; operative time 139 vs. 118 min) and in the neoplasia subgroups (27 vs. 18%; 137 vs. 118 min). No differences between groups were found for rates of reintervention or death. Comparison between LC subgroups showed that the operative time was longer and the conversion rate was higher in the diverticular disease subgroup than in the neoplasia subgroup (155 vs. 137 min; 21 vs. 8%). CONCLUSIONS: In this large cohort of patients undergoing laparoscopic colectomy, LC carried a higher risk than RC of postoperative complications. These findings provide new data on the differences between the two surgeries. Our findings strengthen the notion that right and left colectomies have a different intraoperative and postoperative course and should be analyzed as two separate entities. PMID- 26139497 TI - Various features of laparoscopic tailored resection for gastric submucosal tumors: a single institution's results for 168 patients. AB - BACKGROUND: Laparoscopic resection is a standard procedure for gastric submucosal tumors. Herein, we analyzed the features of various laparoscopic approaches. METHODS: Between January 2007 and November 2013, 168 consecutive patients who underwent laparoscopic resection for gastric submucosal tumors were enrolled. Patients' demographics and clinicopathologic and perioperative data were reviewed retrospectively. RESULTS: Among the 168 patients, exogastric wedge resection was performed in 99 cases (58.9%), single-port intragastric resection was performed in 30 cases (17.9%), eversion technique was used in 17 cases (10.1%), transgastric resection was performed in 8 cases (4.8%), and single-port wedge resection was performed in 6 cases (3.6%). The remaining cases underwent single port exogastric wedge resection, laparoscopic and endoscopic cooperative surgery, or major resection. Mean age was 56.8 +/- 13.3 years, and body mass index was 24.0 +/- 3.2 kg/m(2). Mean operation time was 96.1 +/- 58.9 min; laparoscopic proximal gastrectomy had the longest operation time (3 cases, 291.7 +/- 129.0 min). In contrast, the laparoscopic eversion technique had the shortest operation time (82.6 +/- 32.8 min). Pathologic data revealed a mean tumor size of 2.9 +/- 1.2 cm (with a range of 0.8-8.0 cm). Tumors were most common on the body (98 cases, 58.3%), followed by the fundus (44 cases, 26.2%). Exophytic growth occurred in 39 cases (23.2%), endophytic growth occurred in 89 cases (53.0%), and dumbbell-type growth occurred in 40 cases (23.8%). Gastrointestinal stromal tumors occurred in 130 cases (77.4%), and schwannomas occurred in 23 (13.7%). Thirteen patients had postoperative complications (delayed gastric emptying in 5, stricture in 3, bleeding in 3, others in 2). The mean follow-up period was 28.8 +/- 20.8 months, and there were three recurrences (1.8%) at 6, 19 and 31 months after the initial surgery. CONCLUSIONS: For gastric submucosal tumors with appropriate locations and growth types, laparoscopic tailored resection which facilitates safer and more precise resection can be good alternative treatment option. PMID- 26139498 TI - EUS-guided drainage of pancreatic pseudocysts offers similar success and complications compared to surgical treatment but with a lower cost. AB - BACKGROUND AND AIM: Pancreatic pseudocysts (PPC) are a complication that occurs in acute and chronic pancreatitis. They comprise 75% of cystic lesions of the pancreas. There are scarce data about surgical versus endoscopic treatment on PPC. The aim of this study was to compare both treatment modalities regarding clinical success, complication rate, recurrence, hospital stay and cost. METHODS: Retrospectively, data obtained prospectively from 2000 to 2012 were analyzed. A PPC was defined as a fluid collection in the pancreatic or peripancreatic area that had a well-defined wall and contained no solid debris or recognizable parenchymal necrosis. Clinical success was defined as complete resolution or a decrease in size of the PPC to 2 cm or smaller. RESULTS: Overall, 64 procedures in 61 patients were included: 21 (33%) cases were drained endoscopically guided by EUS and 43 (67%) cases were drained surgically. The clinical success of the endoscopic group was 90.5 versus 90.7% for the surgical group (P = 0.7), with a complication rate of 23.8 and 25.6%, respectively (P = 0.8), and a mortality rate of 0 and 2.3% for each group, respectively (P = 0.4). The hospital stay was lower for the endoscopic group: 0 (0-10) days compared with 7 (2-42) days in the surgical group (P < 0.0001). Likewise, the cost was lower in the endoscopic group (P < 0.001). The recurrence rate was similar in both groups: 9.5 and 4.5% respectively (P = 0.59). The two recurrences found in the endoscopic group were associated with stent migration, and the recurrence in the surgical group was due to the type of surgery performed (open drainage). CONCLUSION: Endoscopic treatment of PPC offers the same clinical success, recurrence, complication and mortality rate as surgical treatment but with a shorter hospital stay and lower costs. PMID- 26139499 TI - Chemocauterization with trichloroacetic acid in congenital and recurrent tracheoesophageal fistula: a minimally invasive treatment. AB - OBJECTIVE: Recurrent tracheoesophageal fistula (RTEF) is a serious complication after primary repair of esophageal atresia and tracheoesophageal fistula (EA/TEF). Treatment of RTEF involved an open surgery by thoracotomy. Technically it is a challenge with a high morbidity and mortality. Congenital tracheoesophageal fistula (CTEF) traditionally involved an open surgery by thoracotomy or cervicotomy. Many endoscopic techniques have been developed since the past decades: thoracoscopic or bronchoscopic approach for the treatment of RTEF and CTEF; nevertheless, optimal treatment is not still determined because of few numbers of patients, short-term follow-up, and different procedures. We report our experience and evaluated the efficacy in the chemocauterization of CTEF and RTEF, with the use of 50% trichloroacetic acid (TCA) as a technique minimally invasive. MATERIALS AND METHODS: From 2010 to 2014, fourteen patients with TEF (twelve RTEF and two CTEF) were selected for endoscopic management in two centers. Twelve patients had RTEF after primary repair of EA/TEF by thoracotomy approach, and two patients had CTEF in the upper pouch, diagnosed after EA/TEF (Type B) long gap, treated by thoracotomy and thoracoscopy, respectively. In all cases the diagnosis was confirmed by esophagram, bronchoscopy, and clinical evaluation. Under general anesthesia, a rigid pediatric bronchoscope with a 0 degrees rod lens telescope and tele-monitoring was used to localize the TEF. Cotton soaked with 50% TCA was applied on the TEF during 30 s, and the procedure was repeated 3 times. The endoscopic treatment was performed monthly until TEF closure was achieved. RESULTS: RTEF and CTEF were closed in all patients. The mean number of procedure in each patient was 1.8. Closure of TEF was confirmed by esophagram, bronchoscopy, and clinical evaluation. There were a bacterial pneumonia and bronchospasm as postoperative complications. Median follow-up was 41 months (8-72). All of these TEF remain completely obliterated, and all patients are asymptomatic. CONCLUSION: Endoscopic management of congenital and recurrent TEF with the use of 50% TCA is as a minimally invasive, effective, simple and safe technique in these patients and avoids the morbidity of open surgery. PMID- 26139500 TI - Comparison of percutaneous extraperitoneal closure (LPEC) and open repair for pediatric inguinal hernia: experience of a single institution with over 1000 cases. AB - BACKGROUND: Recently, laparoscopic percutaneous extraperitoneal closure (LPEC) for pediatric inguinal hernia has become more popular. The aim of this study was to compare LPEC with open repair (OR) performed in one institution. METHODS: In total, 1050 patients underwent OR from July 2003 to June 2008, and 1017 patients underwent LPEC from July 2008 to June 2013. The mean follow-up period was 100 months in OR and 40 months in LPEC (p < 0.01). Given the difference in the follow up periods, the log-rank test was used for the analysis of the long-term results. The mean age at operation in OR and LPEC was 3.72 and 3.75 years, respectively (p = 0.81). The mean body weight was 14.73 and 14.72 kg, respectively (p = 0.98). The male/female ratio was 617/433 and 561/456, respectively (p = 0.10). In the LPEC procedure, the asymptomatic contralateral internal ring was routinely observed, and when a patent processus vaginalis (PPV) was confirmed, prophylactic surgery was performed. RESULTS: The mean operative time for unilateral surgery in OR and LPEC was 28.5 and 21.2 min, respectively (p < 0.01). The mean operative time for bilateral surgery was 52.3 and 25.4 min, respectively (p < 0.01). Recurrence was confirmed in 0.52% in OR and in 0.27% in LPEC (p = 0.53). In the LPEC group, 41.7% of patients with clinically unilateral inguinal hernia were confirmed to have a contralateral PPV and underwent prophylactic LPEC. Contralateral metachronous inguinal hernia (CMIH) was seen in 6.48% in OR and in 0.33% in LPEC (p < 0.01). Two patients showed postoperative testicular atrophy, and two had iatrogenic postoperative cryptorchism after OR, while no postoperative testicular complications were seen after LPEC. CONCLUSION: Both OR and LPEC obtained satisfactory results from the perspective of recurrence rate and complications. Prophylactic contralateral LPEC is useful for preventing CMIH without prolonging operative time compared with OR. The midterm safety and efficacy of LPEC are proven. PMID- 26139501 TI - Relationship between ventral hernia defect area and intra-abdominal pressure: dynamic in vivo measurement. AB - BACKGROUND: It is an acceptable concept that the ventral hernia defect area will increase with a rise in intra-abdominal pressure (IAP). The literature lacks the evidence about how much this increase is in vivo. The aim of this study was to objectively measure the change in the ventral hernia defect area with increasing intra-abdominal pressure. METHODS: In a prospective study of laparoscopic ventral hernia repair, the area of hernia defect was measured from inside the abdomen using a sterile paper ruler. The horizontal (width) and vertical (length) measurements of the defect were taken at two pressure points: (IAP = 8 mmHg) and (IAP = 15 mmHg). The hernia defect area was calculated as an oval shape using a standard formula. RESULTS: Eighteen consecutive patients with a ventral hernia were included in this study (8 males: 10 females). Median age was 60 years (30 81), body mass index (BMI) was 29.9 (22.6-37.6). Changing the IAP significantly, (P < 0.001) changed the values of horizontal and vertical measurements, and the calculated area of the ventral hernia defect. The median calculated defect area, as an oval shape, was 5.6 cm(2) (Q1-Q3 = 3.5-15.5) and 6.9 cm(2) (Q1-Q3 = 4.5 18.7) at 8 and 15 mmHg IAP, respectively. The calculated area of mesh required to cover the defect with a 5 cm overlap increased by a median of 5% (Q1-Q3 = 3-6%). The change in defect area did not differ significantly between obese and non obese patients (P = 0.5). CONCLUSIONS: Dynamic, rather than static, measurements of ventral hernia area during laparoscopy provide a simple way of in vivo objective measurement that helps the surgeon choose the appropriate area of mesh. When choosing mesh area, we support the trend toward a larger overlap of at least 5 cm if less precise methods of measuring defect area are been used. PMID- 26139502 TI - Is a robotic system really better than the three-dimensional laparoscopic system in terms of suturing performance?: comparison among operators with different levels of experience. AB - BACKGROUND: High-quality three-dimensional (3D) vision systems are now available for laparoscopic surgery and may improve surgical performance relative to two dimensional (2D) laparoscopy. It is unclear whether 3D laparoscopy is superior to 3D robotic systems. The effect of surgeon experience on surgical performance with different instruments also remains unclear. This study compared the ability of experienced and inexperienced surgeons to perform a suturing task with 2D laparoscopy, 3D laparoscopy, and a 3D robot. METHODS: The 20 recruited surgeons consisted of experts (>=100 laparoscopic cases, n = 9), surgeons with intermediate experience (20-99 cases, n = 7), and novices (<20 cases, n = 4). All performed a suturing task three times with each instrument. Task failure rates and completion times were measured. RESULTS: All novices failed to complete the task with 2D or 3D laparoscopy, but all completed the task with the robot. The intermediate group failed the task with 2D laparoscopy (23.8% failure rate) more often than with 3D laparoscopy (4.8%) or the robot (0%; P = 0.04). Expert failure rates were low for all instruments. Intermediate group task completion times were similar to 2D laparoscopy (median 312 s; range 229-495 s), 3D laparoscopy (324 s; 170-443 s), and the robot (319 s; 213-433 s) (P = 0.237). The expert times differed significantly (P = 0.01); post hoc analyses showed that their total completion time with 3D laparoscopy (177 s; 126-217 s) was significantly shorter than with 2D laparoscopy (244 s; 155-270 s; P = 0.004). It also tended to be shorter than with the robot (233 s; 187-461 s; P = 0.027). CONCLUSIONS: Novices benefited particularly from the robot. The intermediate group completed the task equally well and equally quickly with 3D laparoscopy and the robot. The experts completed the task equally well regardless of instrument, but their times were much faster with 3D laparoscopy. Thus, well-trained laparoscopic surgeons may not really benefit from 3D robot systems if 3D laparoscopy is available. PMID- 26139503 TI - Acuity, outcomes, and trends in the transfer of surgical patients: a national study. AB - INTRODUCTION: With the regionalization of surgical care, reduction in the rural workforce, rising healthcare costs, and increasing focus on surgical outcomes, appropriate transfer of surgical patients is an increasingly important aspect of health care. This study examines patients transferred for surgical intervention through a national sample. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2012 for surgery patients who were transferred from an outside hospital or emergency department (ED) and compared patients undergoing surgery without transfer. Patients were divided into two time periods (TP): 2005-2008 (TP1) and 2008-2012 (TP2) for analysis; patient characteristics and top CPT codes for each TP were collected. Univariate analysis and matched cohorts were used to compare the groups. RESULTS: Overall, 61,204 patients were transferred and underwent surgery. The rate of transferred surgery patients increased from 3.2% in TP1 to 4.5% in TP2 (p < 0.0001). Compared to non-transferred patients, transferred patients had higher rates of diabetes (23.4 vs. 17.6%, p < 0.0001), tobacco use (27.9 vs. 20.3%, p < 0.0001), Charlson comorbidity index (mean score 1.5 vs. 0.8, p < 0.0001), preoperative sepsis (32.0 vs. 9.4%, p < 0.0001), and need for emergent surgery (41.3 vs. 14.4%, p < 0.0001). From TP1 to TP2, there was an increase in transferred patients who were obese (33.9-36.4%, p < 0.0001) and had emergent transfers (39.6-41.8%, p < 0.0001), with a decrease in diabetic patients (24.7 23.1%, p < 0.0001). From TP1 to TP2, transferred patients had more minor complications (17.7-31.0%, p < 0.0001), but fewer major complications (32.1 23.9%, p < 0.0001) and lower 30-day mortality (11.8-8.1%, p < 0.0001). CONCLUSIONS: Patients transferred for surgery represent a higher acuity population than non-transferred patients, and the number of transfers continues to rise. Even when matched by comorbidities, transferred patients have worse outcomes. Surgical sub-specialization and physician tiering may complicate future transfer practices. Efficient transfers, effective physician communication, and ready availability of medical records are critical in improving patient transfers. PMID- 26139504 TI - Spleen assessment after laparoscopic transperitoneal left adrenalectomy: preliminary results. AB - BACKGROUND: Several laparoscopic approaches to the adrenal gland have been described. We prefer the lateral transabdominal approach. The aim of this study is to evaluate prospectively the presence of any anatomical and dynamic changes in the spleen after laparoscopic transperitoneal left adrenalectomy (LTLA), which can cause an increased risk of early and late complications. METHODS: We have evaluated 21 patients before and 6 months after surgery in order to verify the possible presence of a wandering spleen. A clinical and instrumental follow-up [ultrasound (US), magnetic resonance (MR)] were performed. During US protocol, in supine, right lateral, and orthostatic position, the longitudinal and anteroposterior diameter of the spleen and the resistive index within 3 cm of the origin of the splenic artery in three different measurements averaged were measured. MR protocol evaluated, in supine and right lateral position, the splenic volume and its distances from the diaphragm dome and the lateral margin of the costal arch. RESULTS: p Values calculated for each parameter were not statistically significant. Our results confirm the absence of any anatomical and dynamic changes in the spleen after LTLA. CONCLUSIONS: The most common complications after laparoscopic adrenalectomy are well known and widely described. Our experience does not exclude the occurrence of a wandering spleen, but allows us to state that a rightful mobilization of the pancreaticosplenic block can avoid this event, and in agreement with other authors, the presence of a wandering spleen remains an isolated complication. PMID- 26139505 TI - Heat injury to the inferior vena cava by bipolar tissue sealer. AB - BACKGROUND: Although energy devices have brought big advantages to surgery, there are few reports about disadvantages. We conducted an animal experiment to clarify the thermal effect of the bipolar tissue sealing system, EnsealTM, to adjacent vessels of the inferior vena cava. METHODS: We used an experimental miniature pig for the experiment. After laparotomy and mobilization of the intestine, the inferior vena cava was exposed. We activated the device under two different conditions: In the first group, the so-called contact group (Group C), the blade of EnsealTM touched the surface of the IVC directly. In the other group, referred to as non-contact group (Group N), the blade was held about 1 mm away from the IVC. Activation time of the generator was 5, 10, and 15 s, respectively, in both groups. RESULTS: In Group C, the mean IVC surface temperature was 47.2, 57.6, and 60.4 degrees C for 5, 10, and 15 s, respectively. The difference between the mean temperature of 5 and 15 s is statistically significant. In Group N, no statistical significance was achieved in all time-settings. The muscular layers of the IVC wall in Group C after 10 s of activation were broken, and cell nuclei were shrunken. CONCLUSIONS: When EnsealTM is used, contact with the adjacent vessels of the IVC should be avoided at all. It could increase the risk of heat injury to the vessel wall. PMID- 26139506 TI - An analysis of risk factors for pancreatic fistula after robotic pancreaticoduodenectomy: outcomes from a consecutive series of standardized pancreatic reconstructions. AB - BACKGROUND: Proponents of the robotic platform site its potential advantages in complex reconstructions such as the pancreaticojejunal anastomosis; however, the incidence and risk factors for postoperative pancreatic fistula (POPF) after robotic pancreaticoduodenectomy (RPD) have not been characterized. OBJECTIVE: To identify independent risk factors for POPF after RPD. METHODS: A prospectively maintained database of patients that underwent RPD (2008-2013) with a standardized pancreaticojejunostomy was analyzed. Univariate and multivariate analyses (UVA/MVA) were used to identify independent predictors for POPF. The POPF prognostic scores developed by Braga and Callery for open pancreaticoduodenectomy were then applied with logistic regression analysis on this RPD cohort. RESULTS: One hundred and fifty consecutive RPDs were analyzed. POPF occurred in 26 (17.3%); 13 (8.6%) of which were ISGPF category B and C. On UVA, patients with POPF had larger body mass index (BMI), smaller pancreatic duct diameter, smaller tumor size, longer OR time, larger estimated blood loss (EBL) and RBC transfusion (all p < 0.05). Higher EBL, duct size <4 mm, larger BMI and small tumor size remained the best independent risk factors for POPF on MVA. Increased Callery (OR 1.46, 95% CI, p = 0.001) and Braga (OR 1.2, 95% CI, p = 0.005) scores predicted an increased risk of POPF in this RPD cohort. CONCLUSIONS: Larger BMI, higher EBL, smaller tumor size and smaller duct diameter are the main predictors of POPF in RPD. PMID- 26139507 TI - Short-term and long-term outcomes of single-incision versus multi-incision laparoscopic resection for colorectal cancer: a propensity-score-matched analysis of 214 cases. AB - BACKGROUND: The aim of this study was to reveal the short-term and long-term outcomes of single-incision laparoscopic colorectal resection (SILC) compared with multi-incision laparoscopic colorectal resection (MILC) for colorectal cancer using propensity score matching analysis. METHODS: The study group included 235 patients who underwent SILC and 730 patients who underwent MILC for colorectal cancer between April 2009 and September 2014. The propensity score matching for age, gender, body mass index, tumor location (right-sided colon/sigmoid colon/upper rectum), lymph node dissection (D1/D2/D3), pathologic T (<=T3) stage and TNM (0-I/II/III) stage produced 107 matched pairs. The exclusion criteria for SILC were as follows: (1) tumors located at the transverse, descending colon or lower rectum, (2) stage IV tumors, synchronous or previous malignancies, (3) locally advanced tumors >T4, (4) acute obstructions or previous major abdominal surgery and (5) obese patients: BMI > 30. RESULTS: No significant differences were observed in operating time, bleeding volumes, starting time of liquid diet and length of hospital stay between the SILC and MILC groups. However, the SILC group showed less analgesic requirements (1.1 vs. 1.9 times; p = 0.0006) and shorter length of incision (2.7 vs. 4.3 cm; p = 0.0000) compared to MILC group. The overall rate of postoperative complications was similar in both groups (2.8 vs. 3.7%, p = 0.70). The 5-year overall survival rate of SILC and MILC was 100 and 95% (p = 0.125) and 5-year disease-free survival rates in stages 0-III were 97 and 94% (p = 0.189), 100 and 92% in stage II and 90 and 85% in stage III, respectively. CONCLUSIONS: This study suggests that SILC for colorectal cancer is a safe and feasible option with better cosmetic results and less pain in strictly selected patients. SILC can also produce good oncological results with similar postoperative outcomes to MILC. PMID- 26139509 TI - Complications in a series of 4400 paediatric cochlear implantation. AB - OBJECTIVES: The purpose of this study is to retrospectively review the complications of paediatric patients undergoing cochlear implantation at four major Iranian cochlear implant centres. METHODS: A retrospective analysis was performed of all patients who underwent primary cochlear implantation from January 1991 to December 2013. The patients were reviewed for demographic information, and complications including cerebrospinal fluid leak, meningitis, facial palsy, and wound infection. RESULTS: 4400 records were reviewed. Fifty four patients were lost to follow-up; therefore, 4346 records were analysed. The most common aetiology of hearing loss was non-syndromic genetic sensori-neural hearing loss (69%). Other less common aetiologies of hearing loss included TORCH (Toxoplasmosis, Other infections, Rubella, Cytomegalovirus, Herpes) (11%), syndromic hearing loss (7%), ototoxicity (5%), and autoimmune inner-ear disease (4%). The most common major complications were CSF leak (0.4%), skin necrosis (0.2%), meningitis (0.1%), facial paralysis (0.07%) and massive haemorrhage (0.05). CONCLUSION: Cochlear implantation continues to be reliable and safe in experienced hands, with a very low percentage of severe complications. PMID- 26139508 TI - A Fast Multiple-Kernel Method With Applications to Detect Gene-Environment Interaction. AB - Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multifactor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the "expectation-maximization (EM)" algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous "fastKM" algorithm for multikernel analysis that is based on a low-rank approximation to the nuisance effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level. PMID- 26139510 TI - Securing stent during multi-stage laryngotracheoplasty--an evolved technique. AB - BACKGROUND: Multi-stage laryngotracheoplasty (LTP) typically requires a stent be secured to the airway for 2-6 weeks. Our technique has evolved over time to securing the stent to the strap muscles and tying a series of knots long enough to leave the suture tail protruding through the skin incision, which simplifies stent removal. METHODS: Retrospective chart review. RESULTS: Twenty-four patients underwent multi-stage LTP at our institution from 2007 to 2013. Eight patients were excluded from the study because they either did not have a stent placed (n=4), or they had a t-tube placed which was not sutured in place (n=4). Of the remaining 16 patients, 62.5% (n=10) had their stent secured via sutures which were buried below the skin, and 37.5% (n=6) via a long suture tail which was left protruding through the end of the skin incision. An incision was required for stent removal 100% of buried sutures patients, and 33% of exposed suture patients (p=0.0009). Average operative time for stent removal was 60min in the buried sutures group, and 25min in the exposed sutures group (p=0.0075). CONCLUSIONS: Securing stents via an exposed suture technique decreases the need for making a skin incision during the second stage of the operation, and significantly decreases the operative time of the second stage. PMID- 26139512 TI - Impact of an equality constraint on the class-specific residual variances in regression mixtures: A Monte Carlo simulation study. AB - Regression mixture models are a novel approach to modeling the heterogeneous effects of predictors on an outcome. In the model-building process, often residual variances are disregarded and simplifying assumptions are made without thorough examination of the consequences. In this simulation study, we investigated the impact of an equality constraint on the residual variances across latent classes. We examined the consequences of constraining the residual variances on class enumeration (finding the true number of latent classes) and on the parameter estimates, under a number of different simulation conditions meant to reflect the types of heterogeneity likely to exist in applied analyses. The results showed that bias in class enumeration increased as the difference in residual variances between the classes increased. Also, an inappropriate equality constraint on the residual variances greatly impacted on the estimated class sizes and showed the potential to greatly affect the parameter estimates in each class. These results suggest that it is important to make assumptions about residual variances with care and to carefully report what assumptions are made. PMID- 26139513 TI - Implementation and characterization of flow injection in dissolution dynamic nuclear polarization NMR spectroscopy. AB - The use of dissolution dynamic nuclear polarization (D-DNP) offers substantially increased signals in liquid-state NMR spectroscopy. A challenge in realizing this potential lies in the transfer of the hyperpolarized sample to the NMR detector without loss of hyperpolarization. Here, the use of a flow injection method using high-pressure liquid leads to improved performance compared to the more common gas-driven injection, by suppressing residual fluid motions during the NMR experiment while still achieving a short injection time. Apparent diffusion coefficients are determined from pulsed field gradient echo measurements, and are shown to fall below 1.5 times the value of a static sample within 0.8 s. Due to the single-scan nature of D-DNP, pulsed field gradients are often the only choice for coherence selection or encoding, but their application requires stationary fluid. Sample delivery driven by a high-pressure liquid will improve the applicability of these types of D-DNP advanced experiments. PMID- 26139511 TI - Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils. AB - BACKGROUND: Phospholipase A2s mediate the rate-limiting step in the formation of eicosanoids such as cysteinyl leukotrienes (CysLTs). Group IVA cytosolic PLA2alpha (cPLA2alpha) is thought to be the dominant PLA2 in eosinophils; however, eosinophils also have secreted PLA2 (sPLA2) activity that has not been fully defined. OBJECTIVES: To examine the expression of sPLA2 group X (sPLA2-X) in eosinophils, the participation of sPLA2-X in the formation of CysLTs, and the mechanism by which sPLA2-X initiates the synthesis of CysLTs in eosinophils. METHODS: Peripheral blood eosinophils were obtained from volunteers with asthma and/or allergy. A rabbit polyclonal anti-sPLA2-X antibody identified sPLA2-X by Western blot. We used confocal microscopy to colocalize the sPLA2-X to intracellular structures. An inhibitor of sPLA2-X (ROC-0929) that does not inhibit other mammalian sPLA2s, as well as inhibitors of the mitogen-activated kinase cascade (MAPK) and cPLA2alpha, was used to examine the mechanism of N formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated formation of CysLT. RESULTS: Eosinophils express the mammalian sPLA2-X gene (PLA2G10). The sPLA2-X protein is located in the endoplasmic reticulum, golgi, and granules of eosinophils and moves to the granules and lipid bodies during fMLP-mediated activation. Selective sPLA2-X inhibition attenuated the fMLP-mediated release of arachidonic acid and CysLT formation by eosinophils. Inhibitors of p38, extracellular-signal-regulated kinases 1/2 (p44/42 MAPK), c-Jun N-terminal kinase, and cPLA2alpha also attenuated the fMLP-mediated formation of CysLT. The sPLA2-X inhibitor reduced the phosphorylation of p38 and extracellular-signal regulated kinases 1/2 (p44/42 MAPK) as well as cPLA2alpha during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leading to the formation of CysLT via cPLA2alpha. We further demonstrate that sPLA2-X is activated before secretion from the cell during activation. Short-term priming with IL-13 and TNF/IL-1beta increased the expression of PLA2G10 by eosinophils. CONCLUSIONS: These results demonstrate that sPLA2-X plays a significant role in the formation of CysLTs by human eosinophils. The predominant role of the enzyme is the regulation of MAPK activation that leads to the phosphorylation of cPLA2alpha. The sPLA2-X protein is regulated by proteolytic cleavage, suggesting that an inflammatory environment may promote the formation of CysLTs through this mechanism. These results have important implications for the treatment of eosinophilic disorders such as asthma. PMID- 26139515 TI - Comparison of Left Ventricular Myocardial Structure and Function in Patients with Aortic Stenosis and Those with Pure Aortic Regurgitation. AB - OBJECTIVE: We aimed to support the structural and functional distinction between aortic stenosis (AS) and aortic regurgitation (AR). METHODS: Biopsy specimens taken from 70 selected patients (35 with AS and 35 with AR) undergoing aortic valve replacement (AVR) were analyzed for their cardiomyocyte dimensions and structure, interstitial fibrosis and contractile function. To determine normal values of contractile function, 10 donor hearts were analyzed. RESULTS: Cardiomyocyte diameter was higher in AS than in AR (22.7 +/- 2.2 vs. 13.2 +/- 0.7 um, p < 0.001). Length was higher in AR (121.2 +/- 9.4 vs. 95.6 +/- 3.7 um, p < 0.001). Collagen volume fraction was increased in both AS and AR, but was lower in the AS specimens (7.7 +/- 2.3 vs. 8.9 +/- 2.3, p = 0.01). Myofibril density was reduced in AR (38 +/- 4 vs. 48 +/- 5%, p < 0.001). Cardiomyocyte diameter and length were closely linked to the relative left ventricular (LV) wall thickness (R2 = 0.85, p < 0.001 and R2 = 0.68, p = 0.003). The cardiomyocytes of AS patients had higher Fpassive (6.6 +/- 0.3 vs. 4.6 +/- 0.2 kN/m2, p < 0.001), but their total force was comparable. Fpassive was also significantly higher in AS patients with restrictive rather than pseudo-normal LV filling (7.3 +/- 0.5 vs. 6.7 +/- 0.6, p = 0.004). In AS patients, but not in AR patients, Fpassive showed a significant association with the cardiomyocyte diameter (R2 = 0.88, p < 0.001 vs. R2 = 0.31, p = 0.6). CONCLUSIONS: LV myocardial structure and function differ in AS and AR, allowing for compensative adjustment of the diastolic/systolic properties of the myocardium. (c) 2015 S. Karger AG, Basel. PMID- 26139514 TI - RAD mapping reveals an evolving, polymorphic and fuzzy boundary of a plant pseudoautosomal region. AB - How loss of genetic exchanges (recombination) evolves between sex chromosomes is a long-standing question. Suppressed recombination may evolve when a sexually antagonistic (SA) polymorphism occurs in a partially sex-linked 'pseudoautosomal' region (or 'PAR'), maintaining allele frequency differences between the two sexes, and creating selection for closer linkage with the fully sex-linked region of the Y chromosome in XY systems, or the W in ZW sex chromosome systems. Most evidence consistent with the SA polymorphism hypothesis is currently indirect, and more studies of the genetics and population genetics of PAR genes are clearly needed. The sex chromosomes of the plant Silene latifolia are suitable for such studies, as they evolved recently and the loss of recombination could still be ongoing. Here, we used RAD sequencing to genetically map sequences in this plant, which has a large genome (c. 3 gigabases) and no available whole-genome sequence. We mapped 83 genes on the sex chromosomes, and comparative mapping in the related species S. vulgaris supports previous evidence for additions to an ancestral PAR and identified at least 12 PAR genes. We describe evidence that recombination rates have been reduced in meiosis of both sexes, and differences in recombination between S. latifolia families suggest ongoing recombination suppression. Large allele frequency differences between the sexes were found at several loci closely linked to the PAR boundary, and genes in different regions of the PAR showed striking sequence diversity patterns that help illuminate the evolution of the PAR. PMID- 26139517 TI - Familial TAB2 microdeletion and congenital heart defects including unusual valve dysplasia and tetralogy of fallot. AB - Haploinsufficiency of TAB2 was recently implicated as a cause for a variety of congenital heart defects. Reported cases have genomic deletions of 2-10 Mbs including TAB2 at 6q24-25 are almost always de novo and show variable cardiac and extra cardiac phenotype. We report on an inherited, 281 kb deletion in a three generation family. This is the smallest reported deletion involving TAB2 that segregates with congenital heart defects. Three affected individuals in this family present with myxomatous cardiac valves in addition to structural heart defects commonly associated with TAB2 deletions. Findings from this family support a key role of TAB2 haploinsufficiency in congenital heart defects and expand the phenotypic spectrum of TAB2-microdeletion syndrome. PMID- 26139516 TI - Analysis of PubMed User Sessions Using a Full-Day PubMed Query Log: A Comparison of Experienced and Nonexperienced PubMed Users. AB - BACKGROUND: PubMed is the largest biomedical bibliographic information source on the Internet. PubMed has been considered one of the most important and reliable sources of up-to-date health care evidence. Previous studies examined the effects of domain expertise/knowledge on search performance using PubMed. However, very little is known about PubMed users' knowledge of information retrieval (IR) functions and their usage in query formulation. OBJECTIVE: The purpose of this study was to shed light on how experienced/nonexperienced PubMed users perform their search queries by analyzing a full-day query log. Our hypotheses were that (1) experienced PubMed users who use system functions quickly retrieve relevant documents and (2) nonexperienced PubMed users who do not use them have longer search sessions than experienced users. METHODS: To test these hypotheses, we analyzed PubMed query log data containing nearly 3 million queries. User sessions were divided into two categories: experienced and nonexperienced. We compared experienced and nonexperienced users per number of sessions, and experienced and nonexperienced user sessions per session length, with a focus on how fast they completed their sessions. RESULTS: To test our hypotheses, we measured how successful information retrieval was (at retrieving relevant documents), represented as the decrease rates of experienced and nonexperienced users from a session length of 1 to 2, 3, 4, and 5. The decrease rate (from a session length of 1 to 2) of the experienced users was significantly larger than that of the nonexperienced groups. CONCLUSIONS: Experienced PubMed users retrieve relevant documents more quickly than nonexperienced PubMed users in terms of session length. PMID- 26139518 TI - Factors associated with clinical failure of self-expandable metal stent for malignant gastroduodenal obstruction. AB - OBJECTIVE: Endoscopic self-expandable metal stent (SEMS) placement has emerged as an effective palliative treatment for inoperable malignant gastric outlet obstruction (GOO). In spite of successful stent placement, some patients complain of ongoing dysphagia and vomiting. Most reported data on SEMS to date are about technical success of different types of stents and low complication rates. The aim of this study was to evaluate the associated factors of clinical failure after endoscopic SEMS placement for inoperable malignant GOO. METHODS: A total 122 patients who underwent successful endoscopic SEMS placement for malignant GOO in an academic referral center were included in the analyses. We retrospectively evaluated variables associated with clinical outcomes after successful SEMS placement. RESULTS: The clinical success rate was 81.1%. The common causes of GOO were pancreatic (39%) and gastric cancers (32%). The mean length of the stents (+/- standard deviation) was 10.06 +/- 2.42 cm. Multivariate analysis revealed that gallbladder cancer (p = 0.016, OR 6.486, 95% CI, 1.509-59.655), poor performance status (ECOG >= 3) (p = 0.001, OR 10.200, 95% CI, 2.435-42.721), the presence of carcinomatosis peritonei (p < 0.001, OR 35.714, 95% CI, 5.556 250.000) and the failure of endoscope passage (p = 0.039, OR 6.945, 95% CI, 1.101 43.818). CONCLUSION: Our results suggest that gallbladder cancer, poor performance status (ECOG >= 3) and the presence of carcinomatosis peritonei related with clinical failure of palliative SEMS placement. PMID- 26139520 TI - UV photoexcitation of a dissolved metalloid Ge9 cluster compound and its extensive ultrafast response. AB - Femtosecond pump-probe absorption spectroscopy in tetrahydrofuran solution has been used to investigate the dynamics of a metalloid cluster compound {Ge9[Si(SiMe3)3]3}(-). Upon UV photoexcitation, the transients in the near infrared spectral region showed signatures reminiscent of excess electrons in THF (bound or quasi-free) whereas in the visible part excited state dynamics of the cluster complex dominates. PMID- 26139521 TI - Half of UK hospitals lack essential services for managing acute GI bleeds, inquiry finds. PMID- 26139522 TI - A novel mycovirus from Aspergillus fumigatus contains four unique dsRNAs as its genome and is infectious as dsRNA. AB - We report the discovery and characterization of a double-stranded RNA (dsRNA) mycovirus isolated from the human pathogenic fungus Aspergillus fumigatus, Aspergillus fumigatus tetramycovirus-1 (AfuTmV-1), which reveals several unique features not found previously in positive-strand RNA viruses, including the fact that it represents the first dsRNA (to our knowledge) that is not only infectious as a purified entity but also as a naked dsRNA. The AfuTmV-1 genome consists of four capped dsRNAs, the largest of which encodes an RNA-dependent RNA polymerase (RdRP) containing a unique GDNQ motif normally characteristic of negative-strand RNA viruses. The third largest dsRNA encodes an S-adenosyl methionine-dependent methyltransferase capping enzyme and the smallest dsRNA a P-A-S-rich protein that apparently coats but does not encapsidate the viral genome as visualized by atomic force microscopy. A combination of a capping enzyme with a picorna-like RdRP in the AfuTmV-1 genome is a striking case of chimerism and the first example (to our knowledge) of such a phenomenon. AfuTmV-1 appears to be intermediate between dsRNA and positive-strand ssRNA viruses, as well as between encapsidated and capsidless RNA viruses. PMID- 26139519 TI - Therapeutic interventions to disrupt the protein synthetic machinery in melanoma. AB - Control of the protein synthetic machinery is deregulated in many cancers, including melanoma, to increase the protein production. Tumor suppressors and oncogenes play key roles in protein synthesis from the transcription of rRNA and ribosome biogenesis to mRNA translation initiation and protein synthesis. Major signaling pathways are altered in melanoma to modulate the protein synthetic machinery, thereby promoting tumor development. However, despite the importance of this process in melanoma development, involvement of the protein synthetic machinery in this cancer type is an underdeveloped area of study. Here, we review the coupling of melanoma development to deregulation of the protein synthetic machinery. We examine existing knowledge regarding RNA polymerase I inhibition and mRNA translation focusing on their inhibition for therapeutic applications in melanoma. Furthermore, the contribution of amino acid biosynthesis and involvement of ribosomal proteins are also reviewed as future therapeutic strategies to target deregulated protein production in melanoma. PMID- 26139523 TI - Anomalous behavior of water inside the SecY translocon. AB - The heterotrimeric SecY translocon complex is required for the cotranslational assembly of membrane proteins in bacteria and archaea. The insertion of transmembrane (TM) segments during nascent-chain passage through the translocon is generally viewed as a simple partitioning process between the water-filled translocon and membrane lipid bilayer, suggesting that partitioning is driven by the hydrophobic effect. Indeed, the apparent free energy of partitioning of unnatural aliphatic amino acids on TM segments is proportional to accessible surface area, which is a hallmark of the hydrophobic effect [Ojemalm K, et al. (2011) Proc Natl Acad Sci USA 108(31):E359-E364]. However, the apparent partitioning solvation parameter is less than one-half the value expected for simple bulk partitioning, suggesting that the water in the translocon departs from bulk behavior. To examine the state of water in a SecY translocon complex embedded in a lipid bilayer, we carried out all-atom molecular-dynamics simulations of the Pyrococcus furiosus SecYE, which was determined to be in a "primed" open state [Egea PF, Stroud RM (2010) Proc Natl Acad Sci USA 107(40):17182-17187]. Remarkably, SecYE remained in this state throughout our 450 ns simulation. Water molecules within SecY exhibited anomalous diffusion, had highly retarded rotational dynamics, and aligned their dipoles along the SecY transmembrane axis. The translocon is therefore not a simple water-filled pore, which raises the question of how anomalous water behavior affects the mechanism of translocon function and, more generally, the partitioning of hydrophobic molecules. Because large water-filled cavities are found in many membrane proteins, our findings may have broader implications. PMID- 26139526 TI - KLF6 orchestrates cardiac myocyte-to-fibroblast communication: 'He who has ears to hear, let him hear'. PMID- 26139524 TI - The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea. AB - Proper tissue development requires strict coordination of proliferation, growth, and differentiation. Strict coordination is particularly important for the auditory sensory epithelium, where deviations from the normal spatial and temporal pattern of auditory progenitor cell (prosensory cell) proliferation and differentiation result in abnormal cellular organization and, thus, auditory dysfunction. The molecular mechanisms involved in the timing and coordination of auditory prosensory proliferation and differentiation are poorly understood. Here we identify the RNA-binding protein LIN28B as a critical regulator of developmental timing in the murine cochlea. We show that Lin28b and its opposing let-7 miRNAs are differentially expressed in the auditory sensory lineage, with Lin28b being highly expressed in undifferentiated prosensory cells and let-7 miRNAs being highly expressed in their progeny-hair cells (HCs) and supporting cells (SCs). Using recently developed transgenic mouse models for LIN28B and let 7g, we demonstrate that prolonged LIN28B expression delays prosensory cell cycle withdrawal and differentiation, resulting in HC and SC patterning and maturation defects. Surprisingly, let-7g overexpression, although capable of inducing premature prosensory cell cycle exit, failed to induce premature HC differentiation, suggesting that LIN28B's functional role in the timing of differentiation uses let-7 independent mechanisms. Finally, we demonstrate that overexpression of LIN28B or let-7g can significantly alter the postnatal production of HCs in response to Notch inhibition; LIN28B has a positive effect on HC production, whereas let-7 antagonizes this process. Together, these results implicate a key role for the LIN28B/let-7 axis in regulating postnatal SC plasticity. PMID- 26139525 TI - Spatial and temporal regulation of biosynthesis of the plant immune signal salicylic acid. AB - The plant hormone salicylic acid (SA) is essential for local defense and systemic acquired resistance (SAR). When plants, such as Arabidopsis, are challenged by different pathogens, an increase in SA biosynthesis generally occurs through transcriptional induction of the key synthetic enzyme isochorismate synthase 1 (ICS1). However, the regulatory mechanism for this induction is poorly understood. Using a yeast one-hybrid screen, we identified two transcription factors (TFs), NTM1-like 9 (NTL9) and CCA1 hiking expedition (CHE), as activators of ICS1 during specific immune responses. NTL9 is essential for inducing ICS1 and two other SA synthesis-related genes, phytoalexin-deficient 4 (PAD4) and enhanced disease susceptibility 1 (EDS1), in guard cells that form stomata. Stomata can quickly close upon challenge to block pathogen entry. This stomatal immunity requires ICS1 and the SA signaling pathway. In the ntl9 mutant, this response is defective and can be rescued by exogenous application of SA, indicating that NTL9 mediated SA synthesis is essential for stomatal immunity. CHE, the second identified TF, is a central circadian clock oscillator and is required not only for the daily oscillation in SA levels but also for the pathogen-induced SA synthesis in systemic tissues during SAR. CHE may also regulate ICS1 through the known transcription activators calmodulin binding protein 60g (CBP60g) and systemic acquired resistance deficient 1 (SARD1) because induction of these TF genes is compromised in the che-2 mutant. Our study shows that SA biosynthesis is regulated by multiple TFs in a spatial and temporal manner and therefore fills a gap in the signal transduction pathway between pathogen recognition and SA production. PMID- 26139528 TI - Stomach in Contact with the Bladder: A Sonographic Sign of Left Congenital Diaphragmatic Hernia. AB - The evaluation of the characteristics of the fetal stomach should be part of every routine prenatal ultrasound after 11 weeks. A position that has not been previously described in the literature is the stomach in contact with the bladder. We describe 6 cases with the ultrasonographic finding of the stomach in contact with the bladder, all of them in fetuses with left-sided congenital diaphragmatic hernia. Even though the reasons for this striking position of the stomach are not clear, our series highlights the fact that the visualization of the stomach in contact with the bladder may be a specific sonographic marker of congenital diaphragmatic hernia. PMID- 26139527 TI - State of the Human Proteome in 2014/2015 As Viewed through PeptideAtlas: Enhancing Accuracy and Coverage through the AtlasProphet. AB - The Human PeptideAtlas is a compendium of the highest quality peptide identifications from over 1000 shotgun mass spectrometry proteomics experiments collected from many different laboratories, all reanalyzed through a uniform processing pipeline. The latest 2015-03 build contains substantially more input data than past releases, is mapped to a recent version of our merged reference proteome, and uses improved informatics processing and the development of the AtlasProphet to provide the highest quality results. Within the set of ~20,000 neXtProt primary entries, 14,070 (70%) are confidently detected in the latest build, 5% are ambiguous, 9% are redundant, leaving the total percentage of proteins for which there are no mapping detections at just 16% (3166), all derived from over 133 million peptide-spectrum matches identifying more than 1 million distinct peptides using AtlasProphet to characterize and classify the protein matches. Improved handling for detection and presentation of single amino acid variants (SAAVs) reveals the detection of 5326 uniquely mapping SAAVs across 2794 proteins. With such a large amount of data, the control of false positives is a challenge. We present the methodology and results for maintaining rigorous quality along with a discussion of the implications of the remaining sources of errors in the build. PMID- 26139529 TI - Study on Synthesis and Fluorescence of Novel Benzofused Phenazine pi-Conjugated Skeleton with Coumarin and Isophoron Cores. AB - The novel benzofused phenazine pi-conjugated skeleton with a coumarin and isophoron core was synthesized, characterized, and condensed with suitably substituted active methylene compounds by classical Knoevenagel condensation reaction to obtain novel mono-styryl dyes 6a-6d. These novel styryl dyes have hue varying from yellow to violet. The geometries of the styryl dyes were optimized at B3LYP/6-31G (d) level of theory, and their electronic excitation properties were evaluated using density functional theory. PMID- 26139530 TI - Fluorescence Chemosensor for HSO4 (-) Ion Based on Pyrrole-Substituted Salicylimine Zn (2+) Complex: Nanomolar Detection. AB - A novel pyrrole-substituted salicylimine zinc (II) ion complex has been synthesized and evaluated its anion binding affinity. The probe 4 has high selectivity for HSO4 (-) over other anions in CH3OH:H2O (70:30, v/v) solvent system. The emission intensity of 4 was quenched upon addition of HSO4 (-). The probe 4 is highly selective for HSO4 (-) with a detection limit of 40 nm. Photoinduced electron transfer (PET) is responsible for observed change. The binding affinity of 4 for HSO4 (-) was further authenticated through ratiometric change in absorbance profile. PMID- 26139531 TI - Red Emitting Coumarins: Insights of Photophysical Properties with DFT Methods. AB - Red emitting dyes are of interest in various technological applications. Coumarins, though being an important class of fluorescent molecules, those with red emission, have been rarely studied theoretically. The structural and electronic aspects of three novel red emitting coumarins were studied using DFT and TD-DFT methods. The functionals employed were the hybrid functionals B3LYP, CAM-B3LYP, PBE0 and the highly parameterized empirical functional M06. The geometry at ground state reveals the electron donor N,N-diethylamino group is coplanar with the chromophoric system and the nitrile group induces a red shift to the absorption and emission. The electronic energies and dipole moments were solvent dependent. The basis sets and functionals were benchmarked for their performance with these molecules. B3LYP has been proved to be more efficient in computations whereas the basis sets do not have noticeable effect on the electronic properties. However, adding a polarization function to the basis set has improved the calculation of vertical excitation. The B3LYP functional gives maximum absolute deviation of 0.20 eV in calculating the vertical excitations and 0.18 eV for emission. PMID- 26139532 TI - A Spectroscopy Approach for the Study of the Interaction of Oxovanadium(IV)-Salen Complexes with Proteins. AB - Oxovanadium(IV)-salen complexes bind with bovine serum albumin (BSA) and ovalbumin (OVA) strongly with binding constant in the range 10(4)-10(7) M(-1) at physiological pH (7.4) confirmed using UV-visible absorption, fluorescence spectral and circular dichroism (CD) study. CD results show that the binding of oxovanadium(IV) complexes induces the conformational change with the loss of alpha-helicity in the proteins. Docking studies indicate that mode of binding of oxovanadium(IV)-salen complexes with proteins is hydrophobic in nature. PMID- 26139533 TI - NGS metabarcoding proves successful for quantitative assessment of symbiont abundance: the case of feather mites on birds. AB - Understanding the ecological function of species and the structure of communities is crucial in the study of ecological interactions among species. For this purpose, not only the occurrence of particular species but also their abundance in ecological communities is required. However, abundance quantification of species through morphological characters is often difficult or time/money consuming when dealing with elusive or small taxa. Here we tested the use of next generation sequencing (NGS) for abundance estimation of two species of feather mites (Proctophyllodes stylifer and Pteronyssoides parinus) under five proportions (16:1, 16:4, 16:16, 16:64, and 16:256 mites) against a mock community composed by Proctophyllodes clavatus and Proctophyllodes sylviae. In all mixtures, we retrieved sequence reads from all species. We found a strong linear relationship between 454 reads and the real proportion of individuals in the mixture for both focal species. The slope for Pr. stylifer was close to one (0.904), and the intercept close to zero (-0.007), thus showing an almost perfect correspondence between real and estimated proportions. The slope for Pt. parinus was 0.351 and the intercept 0.307, showing that while the estimated proportion increased linearly relative to real proportions of individuals in the samples, proportions were overestimated at low real proportions and underestimated at larger ones. Additionally, pyrosequencing replicates from each DNA extraction were highly repeatable (R = 0.920 and 0.972, respectively), showing that the quantification method is highly consistent given a DNA extract. Our study suggests that NGS is a promising tool for abundance estimation of feather mites' communities in birds. PMID- 26139535 TI - Myc or no Myc, that is the question. AB - The transcription factor c-MYC functions as the master transcription factor for establishing highly active metabolic states in proliferating cells. c-Myc is essential for rapid proliferation of normal cells and has causal relationship with many cancers, including leukemia and lymphoma. While the expression of c-MYC can be aberrantly driven by genetic abnormalities, such as chromosomal translocations directly involving the MYC locus or mutations of its upstream regulators, how c-MYC expression is induced and amplified in normal lymphocytes in response to antigen stimulation remains elusive. In this issue of The EMBO Journal, Preston et al (2015) report how c-MYC is selectively induced and amplified in the antigen-specific T cells that undergo massive clonal expansion for host protection against pathogen infection. PMID- 26139534 TI - Molecular profiling of CD8 T cells in autochthonous melanoma identifies Maf as driver of exhaustion. AB - T cells infiltrating neoplasms express surface molecules typical of chronically virus-stimulated T cells, often termed "exhausted" T cells. We compared the transcriptome of "exhausted" CD8 T cells infiltrating autochthonous melanomas to those of naive and acutely stimulated CD8 T cells. Despite strong similarities between transcriptional signatures of tumor- and virus-induced exhausted CD8 T cells, notable differences appeared. Among transcriptional regulators, Nr4a2 and Maf were highly overexpressed in tumor-exhausted T cells and significantly upregulated in CD8 T cells from human melanoma metastases. Transduction of murine tumor-specific CD8 T cells to express Maf partially reproduced the transcriptional program associated with tumor-induced exhaustion. Upon adoptive transfer, the transduced cells showed normal homeostasis but failed to accumulate in tumor-bearing hosts and developed defective anti-tumor effector responses. We further identified TGFbeta and IL-6 as main inducers of Maf expression in CD8 T cells and showed that Maf-deleted tumor-specific CD8 T cells were much more potent to restrain tumor growth in vivo. Therefore, the melanoma microenvironment contributes to skewing of CD8 T cell differentiation programs, in part by TGFbeta/IL-6-mediated induction of Maf. PMID- 26139536 TI - mTOR activates the VPS34-UVRAG complex to regulate autolysosomal tubulation and cell survival. AB - Lysosomes are essential organelles that function to degrade and recycle unwanted, damaged and toxic biological components. Lysosomes also act as signalling platforms in activating the nutrient-sensing kinase mTOR. mTOR regulates cellular growth, but it also helps to maintain lysosome identity by initiating lysosomal tubulation through a process termed autophagosome-lysosome reformation (ALR). Here we identify a lysosomal pool of phosphatidylinositol 3-phosphate that, when depleted by specific inhibition of the class III phosphoinositide 3-kinase VPS34, results in prolonged lysosomal tubulation. This tubulation requires mTOR activity, and we identified two direct mTOR phosphorylation sites on UVRAG (S550 and S571) that activate VPS34. Loss of these phosphorylation sites reduced VPS34 lipid kinase activity and resulted in an increase in number and length of lysosomal tubules. In cells in which phosphorylation at these UVRAG sites is disrupted, the result of impaired lysosomal tubulation alongside ALR activation is massive cell death. Our data imply that ALR is critical for cell survival under nutrient stress and that VPS34 is an essential regulatory element in this process. PMID- 26139538 TI - Erratum to: Diagnostics to Look beyond the Normal Appearing Brain Tissue (NABT)? A Neuroimaging Study of Patients with Primary Headache and NABT Using Magnetization Transfer Imaging and Diffusion Magnetic Resonance. PMID- 26139537 TI - Crosstalk between Akt/GSK3beta signaling and dynamin-1 regulates clathrin mediated endocytosis. AB - Clathrin-mediated endocytosis (CME) regulates signaling from the plasma membrane. Analysis of clathrin-coated pit (CCP) dynamics led us to propose the existence of a rate-limiting, regulatory step(s) that monitor the fidelity of early stages in CCP maturation. Here we show that nascent endocytic vesicles formed in mutant cells displaying rapid, dysregulated CME are defective in early endosomal trafficking, maturation and acidification, confirming the importance of this "checkpoint." Dysregulated CME also alters EGF receptor signaling and leads to constitutive activation of the protein kinase Akt. Dynamin-1, which was thought to be neuron specific, is activated by the Akt/GSK3beta signaling cascade in non neuronal cells to trigger rapid, dysregulated CME. Acute activation of dynamin-1 in RPE cells by inhibition of GSK3beta accelerates CME, alters CCP dynamics and, unexpectedly, increases the rate of CCP initiation. CRISPR-Cas9n-mediated knockout and reconstitution studies establish that dynamin-1 is activated by Akt/GSK3beta signaling in H1299 non-small lung cancer cells. These findings provide direct evidence for an isoform-specific role for dynamin in regulating CME and reveal a feed-forward pathway that could link signaling from cell surface receptors to the regulation of CME. PMID- 26139539 TI - [Not Available]. PMID- 26139540 TI - Incidence of cancer in Nairobi, Kenya (2004-2008). AB - Cancer incidence rates are presented for the Nairobi Cancer Registry, a population-based cancer registry (PBCR) covering the population of the capital city of Kenya (3.2 million inhabitants in 2009). Case finding was by active methods, with standard and checks for accuracy and validity. During the period 2004-2008 a total of 8,982 cases were registered comprising 3,889 men (an age standardized incidence rate (ASR) of 161 per 100,000) and 5,093 women (ASR 231 per 1,00,000). Prostate cancer was the most common cancer in men (ASR 40.6 per 100,000) while breast cancer was the most common among women (ASR 51.7 per 100,000). Cervical cancer ranked the second most common cancer among women in Nairobi with an ASR of 46.1 per 100,000, somewhat lower than those of other registries in East Africa region. Breast and cervical cancers accounted for 44% of all cancers in women. Cancer of the oesophagus was common in both sexes, with a slight excess of cases in men (sex ratio 1.3). Unlike other regions in East Africa, the rate of Kaposi sarcoma was relatively low during the period (men 3.6/100,000; women 2.0/100,000). Although incidence rates cannot be calculated for the early years of the registry, the increase in relative frequency of prostate cancer and declines in frequency of Kaposi sarcoma may indicate underlying trends in the risk of these cancers. PMID- 26139542 TI - Antisynthetase antibodies in World Trade Center rescue and recovery workers with inflammatory myositis: comment on the article by Webber et al. PMID- 26139543 TI - Change in tidal volume during cardiopulmonary resuscitation in newborn piglets. AB - INTRODUCTION: The purpose of inflations during cardiopulmonary resuscitation (CPR) is to deliver an adequate tidal volume (VT) to facilitate gas exchange. However, no study has examined VT delivery during chest compression (CC) in detail to understand the effect of CC on lung aeration. The aim of the study was to examine VT changes during CC and their effect on lung aeration. METHODS: Piglets were anaesthetised, instrumented and intubated with zero leak. They were then randomly assigned to CPR using either 3:1 compression:ventilation ratio (C:V) (n=6), continuous CC with asynchronous ventilations (CCaV) (90 CC/min with 30/min asynchronous ventilations) (n=6) or continuous CC superimposed with 30 s sustained inflations (CC+SI) with a CC rate of 120/min (n=5). A respiratory function monitor (NM3, Respironics, Philips, Andover, Massachusetts, USA) was used to continuously measure inspiration tidal volume (VTi) and expirational tidal volume (VTe). ANOVA with Bonferroni post-test were used to compare variables of all three groups. RESULTS: During the inflation in the 3:1 C:V group, the mean (SD) VTi and VTe was 23.5 (5.3) mL/kg and 19.4 (2.7) mL/kg (p=0.16), respectively. During the CC, we observed a significant VT loss in the 3:1 group with VTi and VTe being 4.1 (1.2) mL/kg and 11.1 (3.3) mL/kg (p=0.007), respectively. In the CCaV group, VTe was higher compared with VTi, but this was not significant. In the CC+SI group, a VT gain during each CC with VTi and VTe of 16.3 (3.2) mL/kg and 14 (3) mL/kg (p=0.21), respectively, was observed. CONCLUSIONS: VT delivery is improved using CC+SI compared with 3:1 C:V. This improvement in VT delivery may lead to better alveolar oxygen delivery and lung aeration. PMID- 26139541 TI - Autophagy in synaptic development, function, and pathology. AB - In the nervous system, neurons contact each other to form neuronal circuits and drive behavior, relying heavily on synaptic connections. The proper development and growth of synapses allows functional transmission of electrical information between neurons or between neurons and muscle fibers. Defects in synapse formation or development lead to many diseases. Autophagy, a major determinant of protein turnover, is an essential process that takes place in developing synapses. During the induction of autophagy, proteins and cytoplasmic components are encapsulated in autophagosomes, which fuse with lysosomes to form autolysosomes. The cargoes are subsequently degraded and recycled. However, aberrant autophagic activity may lead to synaptic dysfunction, which is a common pathological characteristic in several disorders. Here, we review the current understanding of autophagy in regulating synaptic development and function. In addition, autophagy-related synaptic dysfunction in human diseases is also summarized. PMID- 26139544 TI - Elimination of primary tumours and control of metastasis with rationally designed bacteriochlorin photodynamic therapy regimens. AB - Photodynamic therapy (PDT) with current photosensitisers focuses on local effects and these are limited by light penetration in tissues. We employ a stable near infrared (NIR) absorbing bacteriochlorin with ca. 8h plasma half-life to increase the depth of the treatment and elicit strong systemic (immune) responses. Primary tumour growth delays and cures of BALB/c and nude mice bearing CT26 mouse colon carcinoma are related to the parameters that control PDT efficacy. The systemic anti-tumour protection elicited by the optimised PDT regimen is assessed by tumour rechallenges and by resistance to the establishment of metastasis after intravenous injection of CT26 cells. The optimised treatment regime offered 86% cure rate in BALB/c mice but no cures in BALB/c nude mice. Cured mice rechallenged over 3 months later with CT26 cells rejected the tumour cells in 67% of the cases. PDT of a subcutaneous CT26 tumour 5days after the additional intravenous injection of CT26 cells very significantly reduced lung metastasis. The PDT regimen optimised for the bacteriochlorin leads to remarkable long-term survival rates, effective immune memory and control of lung metastasis. PMID- 26139545 TI - Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis. AB - BACKGROUND AIMS: End-stage liver diseases frequently require liver transplantation. Cell therapy could be an alternative. This study aimed to analyze whether undifferentiated mesenchymal stromal cells (U-MSCs) or MSC derived hepatocyte-like cells (DHLCs) from adipose tissue (AT), umbilical cord blood (UCB) and bone marrow (BM) would better restore damaged liver. METHODS: AT was obtained from lipo-aspiration, UCB from an Umbilical Cord Blood Bank and BM from a BM Transplantation Unit. AT (collagenase digestion), UCB and BM (Ficoll gradient) were cultured (Dulbecco's modified Eagle's medium, low glucose, FBS) for 3 days. Detached adherent cells, at passage 4, were characterized as MSCs. Genetic stability was investigated by means of telomerase enzyme activity and karyotype. Hepatocyte differentiation protocol was performed with the use of Dulbecco's modified Eagle's medium, hepatocyte growth factor, basic fibroblast growth factor and nicotinamide (7 days); maturation medium (oncostatin, dexamethasone, insulin, transferrin and selenium) was added at 36 days. Hepatogenesis analyses were performed by use of morphology and albumin, AF, tyrosine-aminotransferase and glutamine synthetase gene expression and quantitative reverse transcription-polymerase chain reaction on days 9, 18, 25 and 36. Functionality was assessed through glycogen storage detection, indocyanine green absorption and transplantation procedure. U-MSCs and DHLCs were injected 48 h after induced fulminant hepatitis (intraperitoneal injection of carbon tetrachloride) in SCID/BALB-c mice. Histopathologic analyses were performed on days 7 and 15. Human origin included albumin and CK19 human markers. RESULTS: All MSCs differentiated into functional hepatocyte-like cells, stored glycogen and absorbed indocyanine green. AT-MSC DHLC gene expression was more consistent with a normal hepatogenic-differentiation profile. UCB-MSCs expanded weakly, impairing their use for the transplantation procedure. AT and BM U-MSCs and DHLCs regenerated liver injury equally. Regenerated hepatocytes exhibited human origin. CONCLUSIONS: AT might be the source and U-MSCS the stem cells useful for liver-regenerative therapy. PMID- 26139546 TI - Autologous adipose-derived stem cells attenuate muscular atrophy and protect spinal cord ventral horn motor neurons in an animal model of burn injury. AB - BACKGROUND AIMS: Burn injuries might increase muscle mass loss, but the mechanisms are still unclear. In this study, we demonstrated that burn injury induced spinal cord ventral horn motor neuron (VHMN) apoptosis and subsequently caused muscle atrophy and revealed the potential protection of autologous adipose derived stem cells (ASCs) transplantation on spinal cord VHMNs and muscle against burn injury. METHODS: Third-degree hind-paw burns were established by contact with a 75 degrees C metal surface for 10 seconds. Adipose tissues were harvested from the groin fat pad, expanded in culture and labeled with chloromethyl benzamido/1,1'-dioctadecyl-3,3,3',3'- tetramethyl indocarbocyanine perchlorate. The ASCs were transplanted into the injured hind paw at 4 weeks after burn injury. The lumbar spinal cord, sciatic nerve, gastrocnemius muscle and hind-paw skin were processed for immunofluorescent staining at 4 weeks after transplantation, including terminal deoxynucleotidyl transferase (TUNEL) assay, caspase-3, caspase-9, CD 90 and S100, and the gastrocnemius muscle was evaluated through the use of hematoxylin and eosin staining. RESULTS: Caspase-3-positive, caspase-9-positive and TUNEL-positive cells were significantly increased in the corresponding dermatome spinal cord VHMNs after burn injury. Moreover, the decrease of Schwann cells in sciatic nerve and the increase of denervation atrophy in gastrocnemius muscle were observed. Furthermore, ASCs transplantation significantly attenuated apoptotic death of VHMNs and the area of muscle denervation atrophy in the gastrocnemius muscle fibers. CONCLUSIONS: The animal model of third-degree burns in the hind paw showed significant apoptosis in the corresponding spinal cord VHMNs, which suggests that neuroprotection might be the potentially therapeutic target in burn-induced muscle atrophy. ASCs have potential neuroprotection against burn injuries through its anti-apoptotic effects. PMID- 26139547 TI - Serum-free media formulations are cell line-specific and require optimization for microcarrier culture. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are being investigated as potential cell therapies for many different indications. Current methods of production rely on traditional monolayer culture on tissue-culture plastic, usually with the use of serum-supplemented growth media. However, the monolayer culturing system has scale-up limitations and may not meet the projected hundreds of billions to trillions batches of cells needed for therapy. Furthermore, serum free medium offers several advantages over serum-supplemented medium, which may have supply and contaminant issues, leading to many serum-free medium formulations being developed. METHODS: We cultured seven MSC lines in six different serum-free media and compared their growth between monolayer and microcarrier culture. RESULTS: We show that (i) expansion levels of MSCs in serum free monolayer cultures may not correlate with expansion in serum-containing media; (ii) optimal culture conditions (serum-free media for monolayer or microcarrier culture) differ for each cell line; (iii) growth in static microcarrier culture does not correlate with growth in stirred spinner culture; (iv) and that early cell attachment and spreading onto microcarriers does not necessarily predict efficiency of cell expansion in agitated microcarrier culture. CONCLUSIONS: Current serum-free media developed for monolayer cultures of MSCs may not support MSC proliferation in microcarrier cultures. Further optimization in medium composition will be required for microcarrier suspension culture for each cell line. PMID- 26139548 TI - Pediatric brainstem abscess with hemorrhage mimicking diffuse intrinsic pontine glioma: a case report. AB - PURPOSE: We report a rare case of brainstem abscess with hemorrhage mimicking diffuse intrinsic pontine glioma (DIPG). METHODS: A 7-month-old baby girl presented with lethargy and poor oral feeding. She had the mild fever for 1 month. Brain computed tomography revealed the hypodense lesion in the pons. Brain magnetic resonance images (MRI) showed around 1.4-cm-sized rim-enhanced mass with perilesional edema and internal hemorrhage in the pons. The cerebral blood volume was increased in the rim-enhanced area. The provisional diagnosis was DIPG, but the mass did not show the expansile mass with encasement of the basilar artery on the ventral pons. RESULTS: The biopsy was done via the floor of the fourth ventricle, and the pathologic findings showed the many inflammatory cells and CD68-immunopositive macrophage which were compatible with abscess. The antibiotics with ceftriaxone and metronidazole were administrated for 11 weeks, and the follow-up MRI showed the slightly small enhanced lesion without central necrotic area. Three years later, follow-up MRI revealed the encephalomalacic change and atrophy of the pons. She had the stable neurologic deficit of left facial palsy and right hemiparesis. CONCLUSION: The biopsy could be necessary for pontine lesions without typical radiologic findings of DIPG. PMID- 26139550 TI - [Peripheral artery occlusive disease of the lower limbs: Rapid aggravation in a patient taking nilotinib for chronic myeloid leukemia]. AB - The development of tyrosine kinase inhibitors (TKI) has revolutionized management of patients with chronic myeloid leukemia (CML), transforming this fatal disease into a chronic disease with nearly normal life expectancy. Nilotinib is a second generation TKI targeting the oncoprotein BCR-ABL used in patients in the chronic phase of CML. Several research teams have suggested over recent years that nilotinib might be the causal agent in the development or aggravation of vascular disease, particularly in patients with cardiovascular risk factors or an established cardiovascular disease. We report here the case of a patient who developed severe peripheral arterial disease of the lower limbs that worsened despite optimal medical and surgical care, presenting recurrent re-stenoses after different revascularization techniques (bypass, angioplasty...) associated with aggravation of severe trophic disorders to the point of potentially requiring amputation. Discontinuation of nilotinib enabled a stabilization of the arterial lesions and complete healing of the trophic lesions. This case illustrates the importance of recognizing co-morbid conditions in patients with severe vascular disease and to examine the possibility of drug interactions leading to rapid aggravation of arterial disease with no other cause. Studying the pathophysiological impact of TKIs on the vascular system may open new avenues of research for the investigation of factors triggering arteriosclerosis. PMID- 26139549 TI - Shoulder muscle forces during driving: Sudden steering can load the rotator cuff beyond its repair limit. AB - BACKGROUND: Driving is one of the most common everyday tasks and the rotator cuff muscles are the primary shoulder stabilisers. Muscle forces during driving are not currently known, yet knowledge of these would influence important clinical advice such as return to activities after surgery. The aim of this study is to quantify shoulder and rotator cuff muscle forces during driving in different postures. METHODS: A musculoskeletal modelling approach is taken, using a modified driving simulator in combination with an upper limb musculoskeletal model (UK National Shoulder Model). Motion data and external force vectors were model inputs and upper limb muscle and joint forces were the outputs. FINDINGS: Comparisons of the predicted glenohumeral joint forces were compared to in vivo literature values, with good agreement demonstrated (61 SD 8% body weight mean peak compared to 60 SD 1% body weight mean peak). High muscle activation was predicted in the rotator cuff muscles; particularly supraspinatus (mean 55% of the maximum and up to 164 SD 27 N). This level of loading is up to 72% of mean failure strength for supraspinatus repairs, and could therefore be dangerous for some cases. Statistically significant and large differences are shown to exist in the joint and muscle forces for different driving positions as well as steering with one or both hands (up to 46% body weight glenohumeral joint force). INTERPRETATION: These conclusions should be a key consideration in rehabilitating the shoulder after surgery, preventing specific upper limb injuries and predicting return to driving recommendations. PMID- 26139551 TI - Preserved consciousness in vegetative and minimal conscious states: systematic review and meta-analysis. AB - Active, passive and resting state paradigms using functional MRI (fMRI) or EEG may reveal consciousness in the vegetative (VS) and the minimal conscious state (MCS). A meta-analysis was performed to assess the prevalence of preserved consciousness in VS and MCS as revealed by fMRI and EEG, including command following (active paradigms), cortical functional connectivity elicited by external stimuli (passive paradigms) and default mode networks (resting state). Studies were selected from multiple indexing databases until February 2015 and evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. 37 studies were identified, including 1041 patients (mean age 43 years, range 16-89; male/female 2.1:1; 39.5% traumatic brain injuries). MCS patients were more likely than VS patients to follow commands during active paradigms (32% vs 14%; OR 2.85 (95% CI 1.90 to 4.27; p<0.0001)) and to show preserved functional cortical connectivity during passive paradigms (55% vs 26%; OR 3.53 (95% CI 2.49 to 4.99; p<0.0001)). Passive paradigms suggested preserved consciousness more often than active paradigms (38% vs 24%; OR 1.98 (95% CI 1.54 to 2.54; p<0.0001)). Data on resting state paradigms were insufficient for statistical evaluation. In conclusion, active paradigms may underestimate the degree of consciousness as compared to passive paradigms. While MCS patients show signs of preserved consciousness more frequently in both paradigms, roughly 15% of patients with a clinical diagnosis of VS are able to follow commands by modifying their brain activity. However, there remain important limitations at the single-subject level; for example, patients from both categories may show command following despite negative passive paradigms. PMID- 26139552 TI - Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates. AB - Vascularized composite allografts (VCAs) are technically feasible. Similar to other organ transplants, VCAs are hampered by the toxicity and incomplete efficacy associated with conventional immunosuppression. Complications attributable to calcineurin inhibitors remain prevalent in the clinical cases reported to date, and these loom particularly large given the nonlifesaving nature of VCAs. Additionally, acute rejection remains almost ubiquitous, albeit controllable with current agents. Costimulation blockade offers the potential to provide prophylaxis from rejection without the adverse consequences of calcineurin-based regimens. In this study, we used a nonhuman-primate model of VCA in conjunction with immunosuppressive regimens containing combinations of B7 specific costimulation blockade with and without adhesion blockade with LFA3-Ig to determine what adjunctive role these agents could play in VCA transplantation when combined with more conventional agents. Compared to tacrolimus, the addition of belatacept improved rejection free allograft survival. The combination with LFA3-Ig reduced CD2(hi) memory T cells, however did not provide additional protection against allograft rejection and hindered protective immunity. Histology paralleled clinical histopathology and Banff grading. These data provide the basis for the study of costimulation blockade in VCA in a relevant preclinical model. PMID- 26139553 TI - Update on Medication-Overuse Headache and Its Treatment. AB - OPINION STATEMENT: Medication-overuse headache-i.e., a too-frequent consumption of acute headache medications leading to increased headache frequency and reduced effectiveness of acute and preventive treatments-is a serious medical condition whose pathophysiology still remains incompletely known, which is reflected into a lack of mechanism-based treatments. The first mandatory step in the therapeutic strategy remains withdrawal of the abused drug, preferably abrupt, in concomitance with a detoxification pharmacological regimen to lessen withdrawal symptoms. Intravenous hydration, antiemetics, corticosteroids (prednisone), tranquilizers (benzodiazepine), neuroleptics, and rescue medication (another analgesic than the overused) should be delivered in various combinations, on an inpatient (hospitalization and day hospital) basis or outpatient basis, depending on the characteristics of the specific patient and type of overuse. Inpatient withdrawal should be preferred in barbiturate and opioid overuse, in concomitant depression, or, in general, in patients who have difficulty in stopping the overused medication as outpatients. In contrast, in overuse limited to simple analgesics in highly motivated patients, without high levels of depression and/or anxiety, home detoxification should be chosen. Re-prophylaxis should immediately follow detoxification, ideally with local injections of onabotulinumtoxinA every 3 months or topiramate orally for at least 3 months. Adequate information to patients about the risks of a too-frequent consumption of symptomatic headache medications is essential and should constantly parallel treatment to help preventing relapse after detoxification and re-prophylaxis. PMID- 26139554 TI - Hurricane Katrina: Influence on the Male-to-Female Birth Ratio. AB - OBJECTIVE: This study was carried out in order to ascertain whether or not Hurricane Katrina and related factors (i.e. the amount of rainfall) influenced the male-to-female birth ratio (M/F). MATERIALS AND METHODS: Monthly births by gender for the affected states (Alabama, Florida, Louisiana and Mississippi) for January 2003 to December 2012 were obtained from the Centers for Disease Control and Prevention (CDC Wonder, Atlanta, Ga., USA). Precipitation data was obtained from the US National Weather Service. Ordinary linear logistic regression was used for trend analysis. A p value <=0.05 was taken to represent a statistically significant result. RESULTS: Of the total of 3,903,660 live births, 1,996,966 (51.16%) were male and 1,906,694 (48.84%) were female. Significant seasonal variation was noted (the maximum M/F in May was 1.055, the minimum M/F in September was 1.041, p = 0.0073). There was also a separate and significant rise in M/F 8-10 months after the storm (April to June 2006, peak M/F 1.078, p = 0.0074), which translated to an approximate deficit of 800 girls compared to 46,072 girls born in that period if the M/F increase was theoretically only due to a girls' deficit in the denominator of the ratio. This spike was only present in Alabama, Louisiana and Mississippi, all of which received heavy rainfall. Florida did not receive heavy rainfall and experienced no such M/F spike. CONCLUSION: In this study there was a dose-response relation between the amount of rainfall after Hurricane Katrina and the monthly sex ratio of live births in the US states of Alabama, Louisiana and Mississippi 8-10 months later. The well known yet unexplained distinct sex ratio seasonality may be due to natural or man made radiation contained in the rain. PMID- 26139555 TI - Noise induced reversible changes of cochlear ribbon synapses contribute to temporary hearing loss in mice. AB - CONCLUSION: Noise exposure can cause a decline in cochlear ribbon synapses and result in consequent hearing loss. The reduction of synaptic puncta appears reversible and may contribute to hearing restoration in mice after noise exposure. OBJECTIVE: To detect whether noise induced reversible changes of cochlear ribbon synapses contribute to temporary hearing loss in C57BL/6J mice. METHODS: The mice were assigned randomly to five groups and exposed to white noise at 110 dB SPL for 2 h except the control group. ABR thresholds were acquired before noise exposure (control), immediately following exposure (Day 0), or on Days 4, 7, or 14 after noise exposure. Light microscopy, scanning emission microscopy, and whole mounts examination was utilized to study whether there is morphology change of outer hair cells (OHC), inner hair cells (IHC), or spiral ganglion cells (SGN) due to the 110 dB white noise. Moreover, experimental approaches, including immunostaining and confocal microcopy, were used to detect whether ribbon synapses were the primary targets of noise-induced temporary hearing loss. RESULT: Exposure to 110 dB white noise for 2 h induced TTS in mice, with the maximal ABR threshold elevations seen on the 4(th) day after noise exposure. There were no significant morphological changes in the cochlea. Paralleled changes of pre-synaptic ribbons in both the number and post-synaptic density (PSDs) during this noise exposure were detected. The number of pre synaptic ribbon, post-synaptic density (PSDs), and co-localized puncta correlated with the shifts of ABR thresholds. Moreover, a complete recovery of ABR thresholds and synaptic puncta was seen on the 14(th) day after the noise stimulations. PMID- 26139556 TI - Long-term Results of Repeat Percutaneous Mitral Valvuloplasty: Is it Still a Viable Option? PMID- 26139557 TI - Sarcopenia and body composition in diabetic Charcot osteoarthropathy. AB - BACKGROUND: Treatment of Charcot osteoarthropathy (COA) requires restricted walking and offloading for several months, which lead to fat re-distribution and increased sarcopenia. OBJECTIVES/AIM: To investigate whether subjects with COA have an altered body composition compared to controls. METHODS: Cross-sectional case-control study of people with diabetes with acute or chronic Charcot osteoarthropathy, matched with otherwise healthy people with diabetes. A total of 49 subjects (distribution ~1:1) had a total body DXA-scanning, measuring appendicular lean mass, android/gynoid and truncal/total body fat distribution ratios. RESULTS: Sarcopenia frequency was higher in the total population with diabetes overall (9-40%), compared to normal materials. Using two different models for correlating appendicular lean mass to sarcopenia, there were no differences in sarcopenia-rates between the groups (P=0.413 and 0.948 respectively). There was no significant difference in lean tissue mass between the affected and the unaffected leg in the immobilised subject group (P=0.830). The average fat percentage was (29.4-37.7%) in the population with diabetes, compared to a matching background population (24.5-31.9%), whereas there were no significant differences found between the groups (P=0.065). Neither truncal/total fat percent nor android/gynoid fat percent ratios showed differences between the groups. CONCLUSION: To our knowledge, this is the first published dataset investigating body composition in subjects with Charcot osteoarthropathy. The study population of diabetics were more fat and sarcopenic than normal subjects, whereas no statistically significant impact of Charcot osteoarthropathy was found. PMID- 26139558 TI - Safety, pharmacokinetics, and preliminary efficacy of a specific anti-IL-1alpha therapeutic antibody (MABp1) in patients with type 2 diabetes mellitus. AB - AIMS: The role of the IL-1 system in development of type 2 diabetes is well established. Using an IL-1 receptor antagonist, which blocks IL-1alpha and -beta activity, or by specifically neutralizing IL-1beta, several clinical studies have demonstrated improvement in insulin secretion and glycaemia. However, the role of IL-1alpha remains to be investigated. METHODS: We evaluated the safety and preliminary efficacy of a neutralizing true humanTM monoclonal antibody against IL-1alpha (MABp1) in an open label trial in patients with type 2 diabetes. Seven patients between 50 to 66years with type 2 diabetes mellitus were enrolled in the study. The study subjects received four biweekly intravenous infusions of MABp1 at 1.25mg/kg body weight up to day 60 and were followed up for a total of 90days. RESULTS: Compared to baseline, after the 60-day period of treatment HbA1c was numerically reduced by 0.14+/-0.21% (p=0.15), fasting C-peptide was increased by 88% (p=0.03), pro-insulin by 48% (p=0.03) and insulin numerically increased by 74% (p=0.11). Systolic blood pressure numerically decreased by 11mmHg (p=0.2). Both HbA1c and blood pressure rebounded to baseline levels thirty days after the end of MABp1 application. Treatment with MABp1 was well tolerated, and no adverse events occurred during the study. CONCLUSION: The results point to a role of IL 1alpha in type 2 diabetes and encourage further investigations. (ClinicalTrials.gov number NCT01427699). PMID- 26139559 TI - Suntanning with sunscreens: a comparison with sunbed tanning. AB - BACKGROUND/PURPOSE: Acquiring a tanned skin, either by sunbathing, sunbed use, or a combination of both, is a desirable objective for many people. The objective here was to compare the ultraviolet (UV) exposure resulting from a 2-week vacation spent sunbathing with sunscreen-protected skin, with that from a typical course of 10 sessions on a sunbed. METHODS: A numerical analysis combining data on sunlight and sunbed UV levels, time spent tanning and spectral absorption properties of different types of sunscreen. RESULTS: The analysis showed that unless a sunscreen provides optimal broad-spectrum protection, a 2-week sunbathing vacation that avoids sunburn on sunscreen-protected skin can result in a higher cumulative UV exposure than a typical 10-session sunbed course. The lowest exposures for a given sun protection factor (SPF) are obtained when sunscreen delivers broad-spectrum protection that approaches the ideal of uniform absorption at all wavelengths throughout the UV spectrum. CONCLUSION: In extreme cases of recreational sun exposure where sunscreens providing suboptimal broad spectrum protection are used, the UV insult to the skin is likely to result in higher cumulative exposures than commonly employed sunbed practices. PMID- 26139560 TI - Chicken heat shock protein HSPB1 increases and interacts with alphaB-crystallin in aged skeletal muscle. AB - International trading markets of meat require the animal's age information to prevent cross-contamination of ineligible meat products. Individual livestock age is either evaluated from physiological features or verified by breeding history. However, it remains impossible to perform age verification on meat when a suspicion of error occurred in the importing country. To investigate an age related protein in skeletal muscle of livestock, we compared protein expression among chicken pectoralis major of different ages. Results indicated that the level of expression of chicken HSPB1, one of the small heat shock proteins, was increased in aged muscles. On the other hand, other heat shock proteins, heat shock factors, and myosin heavy chain isoform did not change the expression levels in aged chicken muscle. In addition, we identified that alphaB-crystallin interacted with HSPB1 in aged chicken muscle. These results suggest that HSPB1 protein forms complexes with alphaB-crystallin in aged chicken muscle and suppose to become the candidate of age-related bio-marker for verifying the age of chicken meat. PMID- 26139561 TI - Evaluation of the R-Biopharm RIDA(r)GENE Panton-Valentine leukocidin (PVL) kit for the detection of Staphylococcus aureus PVL from pus samples. AB - Staphylococcus aureus Panton-Valentine leukocidin (PVL) is associated with primary skin and soft-tissue infections (SSTI). We aimed to divert the RIDA(r)GENE PVL kit (RBiopharm) from its intended use on cultures to the detection of PVL-encoding genes directly from pus samples. Performance was compared with that of the in-house PCR method developed by the French National Reference Centre for Staphylococci. From June 2013 to May 2014, pus samples from S. aureus SSTI were tested. Our in-house PCR was performed on parallel cultures as the gold standard, while the RIDA(r)GENE PVL assay was used directly on pus samples from the sterile container, or a swab or an Eswab previously dipped in the pus. The kit specificity was also evaluated with pus samples that grew Streptococcus pyogenes. S. aureus reference strains harboring PVL-encoding genes, including known polymorphisms, were also tested. A total of 56 S. aureus containing pus samples (28 PVL + and 28 PVL-) were collected and analyzed. Sensitivity and specificity of the commercial kit were 96.4 % and 100 % respectively, with equal performance whether tested directly from the sterile container or the Eswab. Sensitivity was lower (67.9 %) when the test was performed from a regular SSTI swab. None of the Streptococcus pyogenes pus samples scored positive (n = 5). Specificity was assessed using reference strains (n = 14); in all strains the PVL gene was correctly detected. This study identified the RIDA(r)GENE PVL kit as an efficient, sensitive, and specific tool for the rapid detection of PVL-encoding genes in pus samples. PMID- 26139562 TI - Histaminergic H3-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow. AB - OBJECTIVE: Betahistine is a histamine-like drug that is considered beneficial in Meniere's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H1-receptor and as an inverse agonist at the H3-receptor, these receptors as well as the adrenergic alpha2-receptor were investigated for betahistine effects on cochlear blood flow. MATERIALS AND METHODS: A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H1-, H3- or alpha2-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. RESULTS: Blockage of the H3- or alpha2-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H3-receptors caused a drop in cochlear blood flow and blood pressure. H1-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. CONCLUSION: Betahistine most likely affects cochlear blood flow through histaminergic H3 heteroreceptors. PMID- 26139563 TI - Changes in the computed tomography (pixel) value of mandibular ramus bone and fixation screws after sagittal split ramus osteotomy. AB - The purpose of this retrospective study was to evaluate the changes in computed tomography (CT) values of ramus bone and screws after sagittal split ramus osteotomy (SSRO) setback surgery. The subjects were 64 patients (128 sides) who underwent bilateral SSRO setback surgery. They were divided into six groups according to the fixation plate type used and the use or not of self-setting alpha-tricalcium phosphate (Biopex): group 1: titanium plate and screws; group 2: titanium plate and screws with Biopex; group 3: poly-l-lactic acid (PLLA) plate and screws; group 4: PLLA plate and screws with Biopex; group 5: uncalcined and unsintered hydroxyapatite particles and poly-l-lactic acid (uHA/PLLA) plate and screws; group 6: PLLA/uHA plate and screws with Biopex. CT values (pixel values) of the lateral cortex, medial cortex, osteotomy site, and screws were measured preoperatively, immediately after surgery, and 1 year postoperatively using horizontal CT images at the mandibular foramen taken parallel to the Frankfort horizontal plane. There were significant differences in the time-course change of pixel values for the lateral cortex (P<0.0001) and the osteotomy site (P<0.0001) among the six groups. This study suggests that the fixation plate type and use of bone alternative material may affect bone quality during the process of bone healing after SSRO. PMID- 26139564 TI - Factors influencing internal jugular vein patency after neck dissection in oral cancer. AB - The objective was to investigate factors influencing internal jugular vein stenosis or occlusion after neck dissection, including the reconstructive procedure. The subjects were 73 patients (81 veins) who underwent a modified radical neck dissection, in which the internal jugular vein was preserved, or an extended supraomohyoid neck dissection (E-SOHND). All procedures were performed by the same surgeon. Internal jugular vein patency was evaluated by contrast enhanced computed tomography. Patency was evaluated in relation to gender, side of dissection, number of pathological lymph node metastases, extracapsular spread of lymph node metastases, radiotherapy, and the reconstruction method (no reconstruction, free flap, or pedicle flap). All internal jugular vein occlusions were on the left side and all except one of these patients underwent radiotherapy. Thus, radiotherapy and left side dissection were significant risk factors for occlusion. Free flap reconstruction was not a risk factor for vein stenosis or occlusion. Patients undergoing reconstruction with pedicled musculocutaneous flaps or E-SOHND were less likely to have vein occlusion. Particular care is required for left neck dissection in patients who have undergone radical neck dissection on the right side. This study suggests that covering the internal jugular vein with the muscle might prevent vein occlusion. PMID- 26139565 TI - Twenty-year follow-up of root filled teeth in a Swedish population receiving high cost dental care. AB - AIM: To study the 20-year survival rate and periapical status of root filled teeth in a Swedish population requiring high-cost dental care and to identify factors related to survival and normal periapical status at follow-up. METHODOLOGY: The study population comprised 104 patients selected from four local health insurance districts with treatment plans including radiographs submitted for approval for reimbursement from the Swedish National Dental Insurance in 1977. In 1998, a clinical and radiographic follow-up examination was conducted, to register the status of 449 teeth identified as root filled at baseline. Differences in tooth survival and periapical status at follow-up, with reference to periapical status and quality of root filling at baseline, were analysed by chi-square tests. Multiple regression analysis was used to describe tooth survival and normal periapical status at follow-up, with the explanatory baseline variables: tooth type, type of restoration, type of post, quality of root filling, periapical status, marginal bone loss and caries. Differences were considered significant at a 5% level. RESULTS: Two hundred and ninety (65%) of the root filled teeth survived at follow-up. Baseline variables associated with low odds for tooth survival were mandibular molar, maxillary premolar, prefabricated posts other than screw posts, severe marginal bone loss, caries and apical periodontitis (AP). Normal periapical status at follow-up was registered in 49% of the root filled teeth. Baseline variables associated with low odds for normal periapical status (high risk for AP) at follow-up were mandibular molar, maxillary premolar, AP, severe marginal bone loss and inadequate root filling quality. Of the root filled teeth with AP at baseline, 42% had been left untreated during the observation period, and at follow-up, the AP persisted in 57% of these teeth. CONCLUSIONS: After 20 years, 65% of the root filled teeth had survived and one-third remained with a sound periapical condition, without any further treatment. Almost half of the APs registered at baseline were left without treatment, and more than half of them persisted after 20 years. PMID- 26139566 TI - Discrepancies on Medication Plans detected in German Community Pharmacies. AB - RATIONALE, AIMS AND OBJECTIVES: A current medication plan was identified as important patient safety factor. Information is needed on how many patients possess such a plan and what problems can be identified with its use. This study tried to define factors that influence accuracy of medication plans and to detect discrepancies from planned and actually administered medication in polypharmacy patients. METHODS: Participants of the 'Apo-AMTS' course in Germany evaluated medication plans from their patients during performing medication reviews in community pharmacies. Discrepancies were defined as additional or missing drugs and deviations in dosage and drug names for Rx drugs and missing or additional self-medication. RESULTS: Eighty per cent of the patients possessed a medication plan mainly written by general practitioners. Only 6.5% of the plans showed no discrepancies. Most discrepancies were seen on medication plans written by medical specialists and general practitioners, mainly name aberrations (41%) followed by additional drugs taken (30%) and prescribed drugs no longer taken (18%). Dosage variance was seen in 11% of all discrepancies. Deviations from the plan were observed frequently with antihypertensives (31.4%), analgesics (11.3%) and antidepressants/hypnotics as well as lipid-lowering drugs (6.7%). Four hundred thirty-three OTC drugs were not listed, mainly analgesics, mineral supplements and laxatives. CONCLUSION: Many patients possess a medication plan but most of these plans showed discrepancies which limits the use as patient safety indicator. Community pharmacies offering medication reviews have an essential position to use the medication plan as a central link between patients and their prescribers, and therefore improve patient safety. PMID- 26139567 TI - Antivitamins B12--A Structure- and Reactivity-Based Concept. AB - B12 -antimetabolites are compounds that counteract the physiological effects of vitamin B12 and related natural cobalamins. Presented here is a structure- and reactivity-based concept of the specific 'antivitamins B12 ': it refers to analogues of vitamin B12 that display high structural similarity to the vitamin and are 'locked chemically' to prevent their metabolic conversion into the crucial organometallic B12 -cofactors. Application of antivitamins B12 to healthy laboratory animals is, thus, expected to induce symptoms of B12 -deficiency. Antivitamins B12 may, hence, be helpful in elucidating still largely puzzling pathophysiological phenomena associated with B12 -deficiency, and also in recognizing physiological roles of B12 that probably still remain to be discovered. PMID- 26139568 TI - Local destruction of superconductivity by non-magnetic impurities in mesoscopic iron-based superconductors. AB - The determination of the pairing symmetry is one of the most crucial issues for the iron-based superconductors, for which various scenarios are discussed controversially. Non-magnetic impurity substitution is one of the most promising approaches to address the issue, because the pair-breaking mechanism from the non magnetic impurities should be different for various models. Previous substitution experiments demonstrated that the non-magnetic zinc can suppress the superconductivity of various iron-based superconductors. Here we demonstrate the local destruction of superconductivity by non-magnetic zinc impurities in Ba0.5K0.5Fe2As2 by exploring phase-slip phenomena in a mesoscopic structure with 119 * 102 nm(2) cross-section. The impurities suppress superconductivity in a three-dimensional 'Swiss cheese'-like pattern with in-plane and out-of-plane characteristic lengths slightly below ~1.34 nm. This causes the superconducting order parameter to vary along abundant narrow channels with effective cross section of a few square nanometres. The local destruction of superconductivity can be related to Cooper pair breaking by non-magnetic impurities. PMID- 26139569 TI - Acquired partial lipodystrophy is associated with increased risk for developing metabolic abnormalities. AB - OBJECTIVE: Acquired partial lipodystrophy (APL) is a rare disorder characterized by progressive selective fat loss. In previous studies, metabolic abnormalities were reported to be relatively rare in APL, whilst they were quite common in other types of lipodystrophy syndromes. METHODS: In this nationwide cohort study, we evaluated 21 Turkish patients with APL who were enrolled in a prospective follow-up protocol. Subjects were investigated for metabolic abnormalities. Fat distribution was assessed by whole body MRI. Hepatic steatosis was evaluated by ultrasound, MRI and MR spectroscopy. Patients with diabetes underwent a mix meal stimulated C-peptide/insulin test to investigate pancreatic beta cell functions. Leptin and adiponectin levels were measured. RESULTS: Fifteen individuals (71.4%) had at least one metabolic abnormality. Six patients (28.6%) had diabetes, 12 (57.1%) hypertrigylceridemia, 10 (47.6%) low HDL cholesterol, and 11 (52.4%) hepatic steatosis. Steatohepatitis was further confirmed in 2 patients with liver biopsy. Anti-GAD was negative in all APL patients with diabetes. APL patients with diabetes had lower leptin and adiponectin levels compared to patients with type 2 diabetes and healthy controls. However, contrary to what we observed in patients with congenital generalized lipodystrophy (CGL), we did not detect consistently very low leptin levels in APL patients. The mix meal test suggested that APL patients with diabetes had a significant amount of functional pancreatic beta cells, and their diabetes was apparently associated with insulin resistance. CONCLUSIONS: Our results show that APL is associated with increased risk for developing metabolic abnormalities. We suggest that close long-term follow-up is required to identify and manage metabolic abnormalities in APL. PMID- 26139571 TI - Proviral DNA as a Target for HIV-1 Resistance Analysis. AB - BACKGROUND: Resistance analysis from viral RNA is restricted to detectable viral load. Therefore, analysis from proviral DNA could help in cases with low-level or suppressed viremia. METHODS: Viral plasma RNA and the corresponding cellular proviral DNA of 78 EDTA samples from 48 therapy-naive (TN) and 30 therapy experienced (TE) HIV-1-infected patients were isolated and analyzed for their resistance profiles in the protease and reverse transcriptase genes. RESULTS: Overall, 175 drug-resistance mutations (DRMs) were detected in 25/30 TE (83.3%) and 5/48 TN (10.4%) samples. The TE patients displayed a mean number of 6.68 DRMs in RNA and 5.20 in DNA. In the TN patients, a mean of 0.8 DRMs was found in RNA and 1.0 in DNA; 75% of the DRMs were detected in RNA and DNA simultaneously. In the TE samples, 76% of the DRMs were detected simultaneously in RNA and DNA, 23% exclusively in RNA and 1% in DNA only. The TN samples revealed a significantly higher frequency of DRMs in DNA than in RNA. CONCLUSIONS: Proviral DNA resistance testing provides additional resistance information for TN patients. It is also a reliable alternative for TE patients with unsuccessful RNA testing and can provide valuable information when no records are available. PMID- 26139570 TI - Rare double sex and mab-3-related transcription factor 1 regulatory variants in severe spermatogenic failure. AB - The double sex and mab-3-related transcription factor 1 (DMRT1) gene has long been linked to sex-determining pathways across vertebrates and is known to play an essential role in gonadal development and maintenance of spermatogenesis in mice. In humans, the genomic region harboring the DMRT gene cluster has been implicated in disorders of sex development and recently DMRT1 deletions were shown to be associated with non-obstructive azoospermia (NOA). In this work, we have employed different methods to screen a cohort of Portuguese NOA patients for DMRT1 exonic insertions and deletions [by multiplex ligation probe assay (MLPA); n = 68] and point mutations (by Sanger sequencing; n = 155). We have found three novel patient-specific non-coding variants in heterozygosity that were absent from 357 geographically matched controls. One of these is a complex variant with a putative regulatory role (c.-223_-219CGAAA>T), located in the promoter region within a conserved sequence involved in Dmrt1 repression. Moreover, while DMRT1 domains are highly conserved across vertebrates and show reduced levels of diversity in human populations, two rare synonymous substitutions (rs376518776 and rs34946058) and two rare non-coding variants that potentially affect DMRT1 expression and splicing (rs144122237 and rs200423545) were overrepresented in patients when compared with 376 Portuguese controls (301 fertile and 75 normozoospermic). Overall our previous and present results suggest a role of changes in DMRT1 dosage in NOA potentially also through a process of gene misregulation, even though DMRT1 deleterious variants seem to be rare. PMID- 26139572 TI - Retrograde intrarenal surgery in the management of symptomatic calyceal diverticular stones: a single center experience. AB - To evaluate the outcome of RIRS in managing symptomatic calyceal diverticular as a minimally invasive option, we retrospectively reviewed the records of 43 patients who underwent RIRS from 2005 to 2014 for symptomatic calyceal diverticular stones. A month after the initial operation, the success rate was (81.4%, 35 patients) of which 21 (48.83%) patients were stone free and 14 (32.6%) patients had clinically insignificant residual fragments (CIRFs), and 90% patients were symptom free. Eight patients (16.6%) had significant residual fragments (>3 mm), five of them became completely stone free after the second procedure, other three patients were symptom free and underwent a routine follow up. The final treatment success rate was 93.0%. The initial success rate in the lower calyx was significantly lower than the other calices (P = 0.040). In addition, the association between the stone size and the initial treatment success was significant (P = 0.036). There was no association between any of our other variables and the success rate. The mean first operative time was 60.95 +/- 12.43 min (range 34-92). No major complication (Clavien III-V) occurred, although there were five minor complications (11.6%) (Clavien I-II). There were no admissions to intensive care or deaths in our series, the mean hospitalization time was 1.77 +/- 0.80 days. The management of calyceal diverticular calculus with RIRS is highly effective and can be accomplished with low morbidity. PMID- 26139573 TI - Spectroscopic and molecular docking studies on the interaction between N-acetyl cysteine and bovine serum albumin. AB - The interaction between N-acetyl cysteine (NAC) and bovine serum albumin (BSA) was investigated by UV-vis, fluorescence spectroscopy, and molecular docking methods. Fluorescence study at three different temperatures indicated that the fluorescence intensity of BSA was reduced upon the addition of NAC by the static quenching mechanism. Binding constant (K(b)) and the number of binding sites (n) were determined. The binding constant for the interaction of NAC and BSA was in the order of 10(3) M(-1), and the number of binding sites was obtained to be equal to 1. Enthalpy (DeltaH), entropy (DeltaS), and Gibb's free energy (DeltaG) as thermodynamic values were also achieved by van't Hoff equation. Hydrogen bonding and van der Waals force were the major intermolecular forces in the interaction process and it was spontaneous. Finally, the binding mode and the binding sites were clarified using molecular docking which were in good agreement with the results of spectroscopy experiments. PMID- 26139574 TI - Clinical Outcomes in Patients with Parkinson's Disease Treated with a Monoamine Oxidase Type-B inhibitor: A Cross-Sectional, Cohort Study. AB - STUDY OBJECTIVE: To evaluate the long-term risk of developing cognitive symptoms (e.g., dementia, hallucinations), dyskinesia, falls, and freezing of gait (FoG) in patients with Parkinson's disease (PD) who received monoamine oxidase type B inhibitors (MAOB-Is) compared with patients who had never received MAOB-Is. DESIGN: Retrospective, cross-sectional, cohort study. SETTING: Academic movement disorders clinic. PATIENTS: One hundred eighty-one patients with idiopathic PD who were receiving MAOB-I therapy on a long-term basis for a minimum of 1 year (MAOB-I current-user cohort) and 121 patients with idiopathic PD who had never received MAOB-I therapy (MAOB-I never-user cohort [control group]) between January 1, 1996, and November 30, 2011. MEASUREMENTS AND MAIN RESULTS: The five study outcome variables were dementia, dyskinesia, falls, FoG, and hallucinations. Baseline and outcome data were collected from medical records. Patients in the MAOB-I current-user group were included only if absence of the specified outcomes was documented at baseline. Adjusted multiple logistic regression analyses were performed to calculate the odds ratios (ORs) for MAOB-I use versus never use on clinical outcomes. MAOB-I treatment was associated with a 44.7% reduced risk of dyskinesia (adjusted OR 0.553, 95% confidence interval 0.314-0.976, p=0.041), with the greatest risk reduction observed after 2 years of treatment. No significant association was noted with MAOB-I use and development of dementia, falls, FoG, or hallucinations. CONCLUSION: Long-term use of MAOB-I therapy was associated with reduced risk of dyskinesia in patients with PD. PMID- 26139575 TI - Thymidine kinases share a conserved function for nucleotide salvage and play an essential role in Arabidopsis thaliana growth and development. AB - Thymidine kinases (TKs) are important components in the nucleotide salvage pathway. However, knowledge about plant TKs is quite limited. In this study, the molecular function of TKs in Arabidopsis thaliana was investigated. Two TKs were identified and named AtTK1 and AtTK2. Expression of both genes was ubiquitous, but AtTK1 was strongly expressed in high-proliferation tissues. AtTK1 was localized to the cytosol, whereas AtTK2 was localized to the mitochondria. Mutant analysis indicated that the two genes function coordinately to sustain normal plant development. Enzymatic assays showed that the two TK proteins shared similar catalytic specificity for pyrimidine nucleosides. They were able to complement an Escherichia coli strain lacking TK activity. 5'-Fluorodeoxyuridine (FdU) resistance and 5-ethynyl 2'-deoxyuridine (EdU) incorporation assays confirmed their activity in vivo. Furthermore, the tk mutant phenotype could be alleviated by nucleotide feeding, establishing that the biosynthesis of pyrimidine nucleotides was disrupted by the TK deficiency. Finally, both human and rice (Oryza sativa) TKs were able to rescue the tk mutants, demonstrating the functional conservation of TKs across organisms. Taken together, our findings clarify the specialized function of two TKs in A. thaliana and establish that the salvage pathway mediated by the kinases is essential for plant growth and development. PMID- 26139576 TI - Prostacyclin receptor (PTGIR) in the porcine endometrium: Regulation of expression and role in luminal epithelial and stromal cells. AB - The prostacyclin (PGI2) signaling pathway plays an important role during early pregnancy in rodents and ruminants. Abundant concentrations of PGI2 were also found in the endometrium and uterine lumen of gilts during the period of implantation. The present study was designed to examine (1) the expression of PGI2 receptor (PTGIR) messenger RNA (mRNA) and protein in the endometrium of cyclic and early-pregnant gilts; (2) possible regulation of endometrial PTGIR gene expression by conceptus products, estradiol and cytokines; (3) the effect of iloprost (a PGI2 analogue) on cAMP formation and the expression of fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF; isoform 164) mRNA in luminal epithelial (LE) and stromal (ST) cells. Increased PTGIR mRNA expression in the endometrium was detected on Days 11 to 12 and 18 to 20 of pregnancy compared with respective days of the estrous cycle (P < 0.05). Moreover, greater PTGIR protein level was observed in pregnant than in cyclic gilts on Days 11 to 12 after estrus (P < 0.05). Gilts with unilateral pregnancy revealed abundant PTGIR expression in the endometrium collected from the gravid uterine horn of Day-11 pregnant gilts compared with the respective horn of cyclic animals (P < 0.01). Both LE and ST cells of the endometrium possess PTGIR protein. Moreover, IL1beta, IFNgamma, and conceptus-exposed medium, but not estradiol, stimulated PTGIR mRNA expression in LE and ST cells in vitro. Activation of PTGIR by incubation of LE and ST cells with iloprost resulted in greater cAMP generation (P < 0.01). Moreover, iloprost increased FGF-2 and VEGF164 mRNA expression in ST (P < 0.05), but not LE cells. In conclusion, this study revealed increased expression of PTGIR in the porcine endometrium during the peri-implantation period and reported a possible regulation of PTGIR abundance by conceptus-derived factors. Moreover, besides its important role in vascular system, PGI2 may promote the expression of proangiogenic genes in the uterine stroma. PMID- 26139577 TI - Transplant immuno-diagnostics: crossmatch and antigen detection. AB - Identifying and monitoring donor-directed anti-human leukocyte antigen antibodies are a rapidly evolving area of solid organ transplantation. Donor-specific antibodies dictate pre-transplant donor choice and donor-recipient matching and underlie much acute and chronic allograft rejection and loss. The evolution of available technology has driven this progress. Early, labor-intensive, whole-cell assays based on complement-dependent cytotoxicity suffered from poor sensitivity and specificity, technical challenges and lack of precision. Sequential improvement in assay performance included anti-human immunoglobulin-enhanced, complement-dependent cytotoxicity techniques followed by cell-based flow cytometry. However, variable specificity and sensitivity inherent in cell-based testing continued to limit flow cytometry. The introduction of solid-phase assays led to a second revolution in histocompatibility testing with the use of purified antigens bound to artificial surfaces rather than whole cells. These techniques augmented sensitivity and specificity to detect even low-titer antibodies to previously undetected antigens. Identification of complement-activating antibodies is being introduced, but current technology is in the developmental stage. While the detection of alloantibodies has improved dramatically, our comprehension of their importance remains imperfect. Variability in methodology and a lack of standardization limits the clinical application of these tests. In spite of the hurdles that remain, antibody-mediated rejection has become a key target to improve graft survival. PMID- 26139578 TI - Predicting risk of the fall among aged adult residents of a nursing home. AB - BACKGROUND: Fall is one of the most important outcomes of geriatric medicine. The European Assessment System (EASY) Care Standard provides a tool for assessing the risk of the falls. We aimed to evaluate the validity of the Easy-Care risk of the falls (ECRF) sub-score among the residents of a large nursing home. METHOD: A longitudinal study was conducted within a maximum of 34 months following up for falling in Kahrizak Charity Foundation. At the baseline the demographic, mental status and the depression data of 194 subjects aged >=60 was collected. The Easy Care standard tools and Performance-Oriented Mobility Assessment (POMA) were also used for data collecting. The time, location, and cause of the falls were recorded immediately after each fall incident. The Correlation between POMA and ECRF scores and the factor analysis of ECRF were considered as the concurrent and construct validity respectively. The Factor affecting the fall occurrence was assessed using the Cox-regression model. RESULT: The mean age of the participants was 76.02 (SD 8.82). Fifty two individuals (27.3%) fell at least once during the mean 756 (SD 187)-day follow up. The Spearman correlation coefficient between ECRF and POMA scores was -0.458 (P<0.01). Three components were detected in the factor analysis of the ECRF. In the univariate Cox-regression model, the hazard ratio was 1.04 (CI: 1.00-1.07) for each score increase of the ECRF. For the six month follow-up, at the ECRF cut-off point two of eight, the sensitivity and specificity were calculated as 85.7% and 64.5% respectively. CONCLUSION: It seems that the ECRF is a valid tool for predicting the next 6 months' fall incidents in older adults. PMID- 26139579 TI - Pilot study on the Chinese version of the Life Space Assessment among community dwelling elderly. AB - PURPOSE: To translate the Life Space Assessment (LSA) into Chinese and to examine the reliability and validity of the Chinese version of the LSA (LSA-C) among community-dwelling elderly. MATERIALS AND METHODS: Data were collected from 100 community-dwelling elderly people (50 males and 50 females) aged over 65 years (72.23+/-5.05) in Shanghai. The criterion convergent validity was evaluated by bivariate Pearson correlation analysis separately between the LSA-C and physical health section of the Short Form 36 Health Survey Questionnaire (SF-36-PH), Activities of Daily Living Scale (ADLs), Instrumental Activities of Daily Living Scale (IADLs), and Mini Physical Performance Test (Mini-PPT). The construct validity was estimated using mental health section of the Short Form 36 Health Survey Questionnaire (SF-36-MH), Geriatric Depression Scale (GDS), and Mini Mental State Examination (MMSE). The test-retest reliability of the LSA-C was tested after two weeks by inter-class correlation method. RESULTS: The test retest reliability of the LSA-C was 0.76. The criterion convergent validity, which was evaluated by bivariate Pearson correlation analysis between the LSA-C and SF-36-PH, IADLs, and Mini-PPT, was 0.595 (P<0.001), 0.567 (P<0.001), and 0.433 (P<0.001), respectively. The construct validity, which was evaluated by the SF-36, GDS, and MMSE, was 0.704 (P<0.001), -0.544 (P<0.001), and 0.424 (P<0.001), respectively. CONCLUSIONS: The LSA-C has acceptable reliability and validity and is significantly correlated with other health evaluation tools with respect to, e.g., health status, daily function, physical performance, presence of depression, and cognitive status. These results demonstrate that the LSA-C can be applied to health evaluations and interventions in community-dwelling elderly in China. PMID- 26139580 TI - Comparison of outcomes of peripheral nerve schwannoma excision in neurofibromatosis type 2 patients and non-neurofibromatosis type 2 patients: A case control study. AB - BACKGROUND: Patients with neurofibromatosis type 2 (NF2) are an important subgroup of patients undergoing peripheral nerve schwannoma excision, however data on their outcomes are lacking. Co-existing peripheral neuropathy can complicate the clinical presentation and recovery in NF2. We designed a study to compare outcomes of peripheral nerve schwannoma excision in NF2 patients with excision of isolated, sporadic schwannomas in non-NF2 patients. METHODS: 30 peripheral nerve schwannoma excisions from 15 NF2 patients were compared to 30 excised isolated schwannomas. These were matched for age, size, nerve and level of involvement. Final outcomes were scored on a scale of 0 (no improvement) to 3 (complete symptom resolution). Data were analysed by McNemars test and Wilcoxen matched pairs test. RESULTS: NF2 patients had multiple lesions and more pre operative weakness (p = 0.041) and sensory loss (p = 0.133) compared to controls. Post-operative neurological morbidity occurred in both groups after schwannoma excision. Final outcome scores of 2.4 in NF2 and 2.2 in controls indicate great improvement or complete resolution in the majority. CONCLUSIONS: Outcomes in the NF2 group are not different to controls, despite NF2 patients having more significant pre-operative deficit and co-existing neuropathology. These findings suggest that surgical intervention should be offered to NF2 patients with peripheral nerve schwannomas. PMID- 26139581 TI - July 2015 at a glance. PMID- 26139582 TI - Resting cardiac power index and prediction of prognosis in heart failure. PMID- 26139583 TI - Cost-effectiveness of natriuretic peptide-based screening and collaborative care: a report from the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) study. AB - AIMS: Prevention of cardiovascular disease and heart failure (HF) in a cost effective manner is a public health goal. This work aims to assess the cost effectiveness of the St Vincent's Screening TO Prevent Heart Failure (STOP-HF) intervention. METHODS AND RESULTS: This is a substudy of 1054 participants with cardiovascular risk factors [median age 65.8 years, interquartile range (IQR) 57.8:72.4, with 4.3 years, IQR 3.4:5.2, follow-up]. Annual natriuretic peptide based screening was performed, with collaborative cardiovascular care between specialist physicians and general practitioners provided to patients with BNP levels >50 pg/mL. Analysis of cost per case prevented and cost-effectiveness per quality-adjusted life year (QALY) gained was performed. The primary clinical endpoint of LV dysfunction (LVD) with or without HF was reduced in intervention patients [odds ratio (OR) 0.60; 95% confidence interval (CI) 0.38-0.94; P = 0.026]. There were 157 deaths and/or emergency hospitalizations for major adverse cardiac events (MACE) in the control group vs. 102 in the intervention group (OR 0.68; 95% CI 0.49-0.93; P = 0.01). The cost per case of LVD/HF prevented was ?9683 (sensitivity range -?843 to ?20 210), whereas the cost per MACE prevented was ?3471 (sensitivity range -?302 to ?7245). Cardiovascular hospitalization savings offset increased outpatient and primary care costs. The cost per QALY gain was ?1104 and the intervention has an 88% probability of being cost effective at a willingness to pay threshold of ?30 000. CONCLUSION: Among patients with cardiovascular risk factors, natriuretic peptide-based screening and collaborative care reduced LVD, HF, and MACE, and has a high probability of being cost-effective. TRIAL REGISTRATION: NCT00921960. PMID- 26139584 TI - Clinical outcomes according to QRS duration and morphology in the Eplerenone in Mild Patients: Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF). AB - AIMS: We examined the relationship between different degrees of QRS prolongation and different QRS morphologies and clinical outcomes in patients with heart failure, reduced ejection fraction (HF-REF), and mild symptoms in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). We also evaluated the effect of eplerenone in these patients according to QRS duration/morphology. METHODS AND RESULTS: Patients were categorized as: QRS duration (ms) (i) <120 (n = 1375); (ii) 120-149 (n = 517); and (iii) >=150 (n = 383), and QRS morphology (i) normal (n = 1252); (ii) left bundle branch block (BBB) (n = 608); and (iii) right BBB/intraventricular conduction defect (IVCD) (n = 415). The outcomes examined were the composite of cardiovascular death or heart failure hospitalization and all-cause mortality. Both abnormal QRS duration and QRS morphology were associated with higher risk, e.g. the rates of the composite outcome were: 10.2, 17.6, and 15.5 per 100 patient-years in the <120, 120-149, and >=150 ms groups, respectively. Eplerenone reduced the risk of the primary outcome and mortality, compared with placebo, consistently across the QRS duration/morphology subgroups. CONCLUSION: We found that even moderate prolongation of QRS duration and right BBB/IVCD were associated with a high risk of adverse outcomes in HF-REF. Eplerenone was similarly effective, irrespective of QRS duration/morphology. PMID- 26139586 TI - Response to Dual Antiplatelet Therapy Does Not Impact Bleeding Risks in Patients Undergoing Oral Surgery after Acute Coronary Syndromes. AB - INTRODUCTION: Oral surgery (OS) in patients on antecedent dual antiplatelet therapy (DAPT) may be associated with extra bleeding risks. Monitoring platelet activity in such patients may be beneficial for safety when performing OS. OBJECTIVES: The aim of this study was to assess whether platelet function during DAPT impacted the risk of bleeding following OS in patients with acute coronary syndromes (ACS). PATIENTS AND METHODS: Patients who required OS on top of DAPT with aspirin and clopidogrel (n = 55) for invasively treated ACS were included. The control group (n = 33) consisted of patients who underwent OS with no antiplatelet agent. Platelet aggregation before OS was assessed with a Multiplate(r) analyzer. Bleeding during OS and at days 1, 3, 7 and 10 after surgery was serially evaluated. RESULTS: All 88 patients completed the study. An incomplete response to aspirin or clopidogrel was observed in 43.6% of the patients. In 11% of the cases, an excessive response to clopidogrel was demonstrated. No excessive bleeding upon OS was exhibited in either group during the entire follow-up. Platelet aggregation values and the use of DAPT did not impact the performance of OS. CONCLUSION: Therapy with clopidogrel and aspirin after ACS does not seem to increase the risk of real-life bleeding following OS, regardless of the platelet activity response to DAPT. (c) 2015 S. Karger AG, Basel. PMID- 26139585 TI - Increasing exercise capacity and quality of life of patients with heart failure through Wii gaming: the rationale, design and methodology of the HF-Wii study; a multicentre randomized controlled trial. AB - AIMS: Exercise is known to be beneficial for patients with heart failure (HF), and these patients should therefore be routinely advised to exercise and to be or to become physically active. Despite the beneficial effects of exercise such as improved functional capacity and favourable clinical outcomes, the level of daily physical activity in most patients with HF is low. Exergaming may be a promising new approach to increase the physical activity of patients with HF at home. The aim of this study is to determine the effectiveness of the structured introduction and access to a Wii game computer in patients with HF to improve exercise capacity and level of daily physical activity, to decrease healthcare resource use, and to improve self-care and health-related quality of life. METHODS AND RESULTS: A multicentre randomized controlled study with two treatment groups will include 600 patients with HF. In each centre, patients will be randomized to either motivational support only (control) or structured access to a Wii game computer (Wii). Patients in the control group will receive advice on physical activity and will be contacted by four telephone calls. Patients in the Wii group also will receive advice on physical activity along with a Wii game computer, with instructions and training. The primary endpoint will be exercise capacity at 3 months as measured by the 6 min walk test. Secondary endpoints include exercise capacity at 6 and 12 months, level of daily physical activity, muscle function, health-related quality of life, and hospitalization or death during the 12 months follow-up. CONCLUSION: The HF-Wii study is a randomized study that will evaluate the effect of exergaming in patients with HF. The findings can be useful to healthcare professionals and improve our understanding of the potential role of exergaming in the treatment and management of patients with HF. TRIAL REGISTRATION: NCT01785121. PMID- 26139587 TI - My Interventional Drug-Eluting Stent Educational App (MyIDEA): Patient-Centered Design Methodology. AB - BACKGROUND: Patient adherence to medication regimens is critical in most chronic disease treatment plans. This study uses a patient-centered tablet app, "My Interventional Drug-Eluting Stent Educational App (MyIDEA)." This is an educational program designed to improve patient medication adherence. OBJECTIVE: Our goal is to describe the design, methodology, limitations, and results of the MyIDEA tablet app. We created a mobile technology-based patient education app to improve dual antiplatelet therapy adherence in patients who underwent a percutaneous coronary intervention and received a drug-eluting stent. METHODS: Patient advisers were involved in the development process of MyIDEA from the initial wireframe to the final launch of the product. The program was restructured and redesigned based on the patient advisers' suggestions as well as those from multidisciplinary team members. To accommodate those with low health literacy, we modified the language and employed attractive color schemes to improve ease of use. We assumed that the target patient population may have little to no experience with electronic tablets, and therefore, we designed the interface to be as intuitive as possible. RESULTS: The MyIDEA app has been successfully deployed to a low-health-literate elderly patient population in the hospital setting. A total of 6 patients have interacted with MyIDEA for an average of 17.6 minutes/session. CONCLUSIONS: Including patient advisers in the early phases of a mobile patient education development process is critical. A number of changes in text order, language, and color schemes occurred to improve ease of use. The MyIDEA program has been successfully deployed to a low-health literate elderly patient population. Leveraging patient advisers throughout the development process helps to ensure implementation success. PMID- 26139588 TI - Drosophila model of Meier-Gorlin syndrome based on the mutation in a conserved C Terminal domain of Orc6. AB - Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, primordial dwarfism, small ears, and skeletal abnormalities. Patients with MGS often carry mutations in the genes encoding the components of the pre replicative complex such as Origin Recognition Complex (ORC) subunits Orc1, Orc4, Orc6, and helicase loaders Cdt1 and Cdc6. Orc6 is an important component of ORC and has functions in both DNA replication and cytokinesis. Mutation in conserved C-terminal motif of Orc6 associated with MGS impedes the interaction of Orc6 with core ORC. In order to study the effects of MGS mutation in an animal model system we introduced MGS mutation in Orc6 and established Drosophila model of MGS. Mutant flies die at third instar larval stage with abnormal chromosomes and DNA replication defects. The lethality can be rescued by elevated expression of mutant Orc6 protein. Rescued MGS flies are unable to fly and display multiple planar cell polarity defects. (c) 2015 Wiley Periodicals, Inc. PMID- 26139589 TI - PLA2-responsive and SPIO-loaded phospholipid micelles. AB - PLA2-responsive and superparamagnetic iron oxide (SPIO) nanoparticle-loaded phospholipid micelles were developed. The release of a phospholipid-conjugated dye from these micelles was triggered due to phospholipid degradation by phospholipase A2. The high relaxivity of the encapsulated SPIO could enable non invasive magnetic resonance imaging. PMID- 26139590 TI - Incidence and predictors of in-hospital non-cardiac death in patients with acute heart failure. AB - BACKGROUND: Patients with acute heart failure (AHF) commonly have multiple co morbidities, and some of these patients die in the hospital from causes other than aggravated heart failure. However, limited information is available on the mode of death in patients with AHF. Therefore, the present study was performed to determine the incidence and predictors of in-hospital non-cardiac death in patients with AHF, using the Acute Decompensated Heart Failure Syndromes (ATTEND) registry Methods: The ATTEND registry included 4842 consecutive patients with AHF admitted between April 2007-September 2011. The primary endpoint of the present study was in-hospital non-cardiac death. A stepwise regression model was used to identify the predictors of in-hospital non-cardiac death. RESULTS: The incidence of all-cause in-hospital mortality was 6.4% ( n=312), and the incidence was 1.9% ( n=93) and 4.5% ( n=219) for non-cardiac and cardiac causes, respectively. Old age was associated with in-hospital non-cardiac death, with a 42% increase in the risk per decade (odds 1.42, p=0.004). Additionally, co-morbidities including chronic obstructive pulmonary disease (odds 1.98, p=0.034) and anaemia (odds 1.17 (per 1.0 g/dl decrease), p=0.006) were strongly associated with in-hospital non cardiac death. Moreover, other predictors included low serum sodium levels (odds 1.05 (per 1.0 mEq/l decrease), p=0.045), high C-reactive protein levels (odds 1.07, p<0.001) and no statin use (odds 0.40, p=0.024). CONCLUSIONS: The incidence of in-hospital non-cardiac death was markedly high in patients with AHF, accounting for 30% of all in-hospital deaths in the ATTEND registry. Thus, the prevention and management of non-cardiac complications are vital to prevent acute phase mortality in patients with AHF, especially those with predictors of in hospital non-cardiac death. PMID- 26139591 TI - Effects on length of stay and costs with same-day retransfer to the referring hospitals for patients with acute coronary syndrome after angiography and/or percutaneous coronary intervention. AB - BACKGROUND: Fast track interventions may generate benefits for patients and hospitals by representing a potential for shorter hospital stay. The aim of this study was to investigate how same-day retransfers to the referring hospital after angiographic examination and/or percutaneous coronary intervention (PCI) at the PCI centre affected length of stay and hospital treatment costs for patients with acute coronary syndrome. METHODS AND RESULTS: Three hundred and ninety-nine consecutive admitted patients were prospectively randomized to ordinary care with overnight stay or fast track with same-day retransfer. Length of stay at both the PCI centre and the referring hospital after the stay at the PCI centre were recorded. Costs at the PCI centre related to examinations and treatments were also collected. The ordinary care group included 206 patients and the fast track group 193 patients. Forty-six per cent underwent PCI and 10% coronary artery bypass graft (CABG) in the ordinary care group. In the fast track group 40% had PCI and 6% CABG. Length of stay was reduced at the PCI centre from a median 1.25 days for the ordinary care group to median 0.24 days for the FT group (p<0.001). Length of stay at the PCI centre was significantly reduced after selective coronary angiography and PCI but not for patients undergoing CABG. No significant difference was identified in length of stay for the referring hospitals. Total median treatment costs were reduced from NOK23,657 (US$3838) for the ordinary care group to NOK15,730 (US$2552) for the fast track group (p<0.001). The main contributor to this reduction was shorter length of stay and the corresponding reduction in ward costs at the PCI centre. CONCLUSIONS: We conclude that fast track intervention with same-day retransfer for patients with acute coronary syndrome to the referring hospital reduced length of stay and the hospital treatment costs for patients undergoing selective coronary angiography and PCI. PMID- 26139592 TI - Early invasive versus early conservative strategy in non-ST-elevation acute coronary syndrome: An outcome research study. AB - BACKGROUND: An early invasive strategy (EIS) has been shown to yield a better clinical outcome than an early conservative strategy (ECS) in patients with non ST-elevation acute coronary syndromes (NSTEACSs), particularly in those at higher risk according to the GRACE risk score. However, findings of the clinical trials have not been confirmed in registries. OBJECTIVE: To investigate the outcome of patients with NSTEACS treated according to an EIS or a ECS in a real-world all comers outcome research study. METHODS: The primary hypothesis of the study was the non-inferiority of an ECS in comparison with an EIS as to a combined primary end-point of death, non-fatal myocardial infarction and hospital readmission for acute coronary syndromes at one year. Participating centres were divided into two groups: those with a pre-specified routine EIS and those with a pre-specified routine ECS. Two statistical analyses were performed: a) an 'intention to treat' analysis: all patients were considered to be treated according to the pre specified routine strategy of that centre; b) a 'per protocol' analysis: patients were analysed according to the actual treatment applied. Cox model including propensity score correction was applied for all analyses. RESULTS: The intention to treat analysis showed an equivalence between EIS and ECS (11.4% vs. 11.1%) with regard to the primary end-point incidence at one year. In the three subgroups of patients according to the GRACE risk score (? 108, 109-140, > 140), EIS and ECS confirmed their equivalence (5.3% vs. 3.9%, 8.4% vs. 7.6%, and 20.3% vs. 20.9%, respectively). When the per protocol analysis was applied, a reduction of the primary end-point at one year with EIS vs. ECS was demonstrated (6.2% vs. 15.3%, p=0.021); analysis of the subgroups according to the GRACE risk score numerically confirmed these data (3.1% vs. 6.5%, 5.1% vs. 10.0%, and 10.8% vs. 24.5%, respectively). CONCLUSIONS: In a real-life registry of all-comers NSTEACS patients, ECS was non-inferior to EIS; however, when EIS was applied according to clinical judgement, a reduction of clinical events at one year was demonstrated. PMID- 26139593 TI - Ion Exchange and Antibiofouling Properties of Poly(ether sulfone) Membranes Prepared by the Surface Immobilization of Bronsted Acidic Ionic Liquids via Double-Click Reactions. AB - Bronsted acidic ionic liquids (BAILs) are unique ionic liquids that display chemical structures similar to zwitterions, and they were typically used as solvents and catalysts. In this work, an imidazole-based BAIL monolayer was fabricated onto poly(ether sulfone) (PES) membranes via surface clicking reactions, and the multifunctionality, including ion exchange and biofouling resistance to proteins and bacteria, was demonstrated, which was believed to be one of few works in which BAIL had been considered to be a novel fouling resistance layer for porous membranes. The successful immobilization of the BAILs onto a membrane surface was confirmed by X-ray photoelectron spectroscopy analysis, contact angle measurement, and zeta potential determination. The results from Raman spectroscopy showed that, as a decisive step prior to zwitterion, the BAIL was deprotonated in aqueous solution, and biofouling resistance to proteins and bacteria was found. However, BAIL displayed ion exchange ability at lower pH, and surface hydrophilicity/hydrophobicity of membranes could be tuned on purpose. Our results have demonstrated that the BAIL grafted onto membranes will not only act as an antibiofouling barrier like zwitterions but also provide a platform for surface chemical tailoring by ion exchange, the property of which will become especially important in acidic solutions where the fouling resistance performances of zwitterions are greatly weakened. PMID- 26139595 TI - Feasibility of using a particle counter or flow-cytometer for bacterial enumeration in the assimilable organic carbon (AOC) analysis method. AB - Assimilable organic carbon (AOC) is one of the major determinants of microbial growth and stability in drinking water distribution systems. Nevertheless, AOC measurements are rarely conducted in practice owing, in part, to the tedious and time-consuming nature of the bioassay. Herein, we compared three alternative cell count approaches [flow cytometry with staining (FC-S), flow cytometry without staining (FC-NS), and particle counting (Coulter counter; CC)] for bacterial enumeration as a means to expedite the AOC bioassay. Our results suggest that of the three methods only FC-S provides a suitable alternative to plate counting for rapid and accurate enumeration of both P17 and NOX in the AOC bioassay. While the cell counts obtained by FC-NS were linearly correlated with those obtained using the traditional heterotrophic plate count (HPC) method (FC-NS: R(2) = 0.89-0.96), the AOC values obtained by FC-NS were overestimated by 18-57 %. The CC approach was unsuccessful in enumerating Spirillum strain NOX cells because of the relatively small size of that organism. The CC counts were linearly correlated with HPC for Pseudomonas fluorescens strain P-17 (P17) cells (R(2) = 0.83) but like FC-NS, the CC approach also overestimated the AOC values (for P-17). The advantage of the FC-S method over the other two is improved sensitivity and the ability to specifically enumerate whole cells (and likely viable) as opposed to non-viable cells, cell debris, and other contaminating particles introduced by the test water itself or sample handling. PMID- 26139594 TI - Protective Effect of Lupeol Against Lipopolysaccharide-Induced Neuroinflammation via the p38/c-Jun N-Terminal Kinase Pathway in the Adult Mouse Brain. AB - Recent studies have demonstrated a close interaction between neuroinflammatory responses, increased production of inflammatory mediators, and neurodegeneration. Pathological findings in neurological diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease have shown common signs of neuroinflammation and neurodegeneration. Lupeol, a natural pentacyclic triterpene, has revealed a number of pharmacological properties including an anti inflammatory activity. This study aimed to evaluate the effect of lupeol against lipopolysaccharide (LPS)-induced neuroinflammation in the cortex and hippocampus of adult mice. Our results showed that systemic administration of LPS induced glial cell production of proinflammatory cytokines, tumor necrosis factor (TNF) alpha, inducible nitric oxide synthase (iNOS), and interleukin (IL)-1beta, while co-treatment with lupeol significantly inhibited the LPS-induced activation of microglia and astrocytes, and decreased the LPS-induced generation of TNF-alpha, iNOS, and IL-1beta. The intracellular mechanism involved in the LPS-induced activation of inflammatory responses includes phosphorylation of P38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which was significantly inhibited by lupeol. We further elucidated that lupeol inhibited the LPS-induced activation of the mitochondrial apoptotic pathway and reversed the LPS-induced expression of apoptotic markers such as Bax, cytochrome C, caspase-9, and caspase-3. Taken together; our results suggest that lupeol inhibits LPS-induced microglial neuroinflammation via the P38-MAPK and JNK pathways and has therapeutic potential to treat various neuroinflammatory disorders. PMID- 26139597 TI - California ends vaccine exemptions on grounds of belief--will other states follow? PMID- 26139596 TI - A Pilot Study of the FRAIL Scale on Predicting Outcomes in Chinese Elderly People With Type 2 Diabetes. AB - OBJECTIVE: To determine the prevalence of frailty in older diabetic inpatients using the FRAIL scale and to evaluate the association of frailty with physical function and diabetic vascular complications, as well as its relationship to hospitalization and mortality. METHODS: This pilot study was conducted at the Center of Gerontology and Geriatrics, West China Hospital. A total of 146 inpatients aged 60 years or older with type 2 diabetes were enrolled between December 2011 and October 2012, and participants were followed until December 2013. Frailty, functional status, diabetic nephropathy, and macroangiopathy were assessed at enrollment. The longitudinal outcomes were hospitalization and mortality. Frailty was determined by the 5-item FRAIL scale. Functional status was determined using activities of daily living (ADLs), instrumental activities of daily living (IADLs), and timed "Up and Go" test (TUG). RESULTS: At baseline, 47.2% of participants were robust, 37.7% were prefrail, and 15.1% were frail. After adjusting for age, gender, MMSE score, body mass index (BMI), and the duration and severity of diabetes, both prefrailty and frailty were significantly associated with ADL disability (odds ratio [OR] 2.84 and 6.58, respectively), mobility impairment (OR 3.89 and 22.15, respectively), and diabetic nephropathy (OR 4.31 and 4.46, respectively). In the year after enrollment, the proportion of participants with 3 or more hospitalizations was 16.0% among robust participants, 23.6% among prefrail participants, and 40.9% among frail participants. Being frail predicted a greater number of hospitalizations (OR 5.99). There was no cumulative mortality for robust participants, whereas 3.6% of prefrail participants and 22.7% of frail participants died during follow-up (P < .001). CONCLUSION: In older diabetic inpatients in China, frailty is an independent risk factor for adverse health outcomes. Clinicians could use the FRAIL scale to regularly identify individuals who are frail or who are at risk of becoming frail. PMID- 26139598 TI - Superficial siderosis following spontaneous intracranial hypotension. PMID- 26139599 TI - Citizens unite for computational immunology! AB - Recruiting volunteers who can provide computational time, programming expertise, or puzzle-solving talent has emerged as a powerful tool for biomedical research. Recent projects demonstrate the potential for such 'crowdsourcing' efforts in immunology. Tools for developing applications, new funding opportunities, and an eager public make crowdsourcing a serious option for creative solutions for computationally-challenging problems. Expanded uses of crowdsourcing in immunology will allow for more efficient large-scale data collection and analysis. It will also involve, inspire, educate, and engage the public in a variety of meaningful ways. The benefits are real - it is time to jump in! PMID- 26139600 TI - Socio-demographic, clinical, and health-related factors associated with breast reconstruction - A nationwide cohort study. AB - We collected registry- and questionnaire-based data on socio-economic and health status, tumor- and treatment-related variables, and explored associations with receipt of reconstruction and information about treatment options in a nationwide cohort of Danish women, treated for primary breast cancer. A total of 594 women were available for analysis, 240 (40%) of these received reconstruction. Multivariate analyses showed that receipt of reconstruction was associated with 1) younger age at time of primary surgery (<36 years: OR = 10.04, [3.80-26.50], p < 0.001 and 36-49 years: OR = 2.48, [1.73-3.56], p < 0.001, compared to 50-60 year olds), 2) having received radiotherapy (OR = 0.57, [0.40-0.81], p = 0.002), 3) high income (Second quartile: OR = 1.74, [1.05-2.90], p = 0.033 and fourth quartile: OR = 2.18, [1.31-3.62], p = 0.003, compared with the lowest income quartile), and 4) ethnicity other than Danish (OR = 6.32, [1.58-25.36], p = 0.009). Health-related factors at the time of primary surgery (physical functioning, body mass index, smoking, use of alcohol, and comorbidity) were not associated with reconstruction. Odds of having received information about the option of reconstruction decreased by 8% per year of age in the multivariate analysis (OR = 0.92, [0.87-0.97], p = 0.003). In conclusion, younger age and not having been treated with radiotherapy was independently associated with reconstruction. In addition, higher income was also found to be associated with reconstruction despite free and equal access to reconstruction and healthcare in Denmark. Healthrelated factors were not associated with the use of reconstruction following mastectomy. Our findings underscore the need for physicians to ensure optimal level of information and accessibility to reconstruction for all women regardless of age, treatment, and socio-economic status. PMID- 26139602 TI - Cyclin-dependent kinase-mediated Sox2 phosphorylation enhances the ability of Sox2 to establish the pluripotent state. AB - Sox2 is a key factor in maintaining self-renewal of embryonic stem cells (ESCs) and adult stem cells as well as in reprogramming differentiated cells back into pluripotent or multipotent stem cells. Although previous studies have shown that Sox2 is phosphorylated in human ESCs, the biological significance of Sox2 phosphorylation in ESC maintenance and reprogramming has not been well understood. In this study we have identified new phosphorylation sites on Sox2 and have further demonstrated that Cdk2-mediated Sox2 phosphorylation at Ser-39 and Ser-253 is required for establishing the pluripotent state during reprogramming but is dispensable for ESC maintenance. Mass spectrometry analysis of purified Sox2 protein has identified new phosphorylation sites on two tyrosine and six serine/Threonine residues. Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser-39 and Ser-253 in vitro. Surprisingly, Sox2 phosphorylation at Ser-39 and Ser-253 is dispensable for ESC self-renewal and cell cycle progression. In addition, Sox2 phosphorylation enhances its ability to establish the pluripotent state during reprogramming by working with Oct4 and Klf4. Finally, Cdk2 can also modulate the ability of Oct4, Sox2, and Klf4 in reprogramming fibroblasts back into pluripotent stem cells. Therefore, this study has for the first time demonstrated that Sox2 phosphorylation by Cdk2 promotes the establishment but not the maintenance of the pluripotent state. It might also help explain why the inactivation of CDK inhibitors such as p53, p21, and Arf/Ink4 promotes the induction of pluripotent stem cells. PMID- 26139601 TI - Loss of Liver Kinase B1 (LKB1) in Beta Cells Enhances Glucose-stimulated Insulin Secretion Despite Profound Mitochondrial Defects. AB - The tumor suppressor liver kinase B1 (LKB1) is an important regulator of pancreatic beta cell biology. LKB1-dependent phosphorylation of distinct AMPK (adenosine monophosphate-activated protein kinase) family members determines proper beta cell polarity and restricts beta cell size, total beta cell mass, and glucose-stimulated insulin secretion (GSIS). However, the full spectrum of LKB1 effects and the mechanisms involved in the secretory phenotype remain incompletely understood. We report here that in the absence of LKB1 in beta cells, GSIS is dramatically and persistently improved. The enhancement is seen both in vivo and in vitro and cannot be explained by altered cell polarity, increased beta cell number, or increased insulin content. Increased secretion does require membrane depolarization and calcium influx but appears to rely mostly on a distal step in the secretion pathway. Surprisingly, enhanced GSIS is seen despite profound defects in mitochondrial structure and function in LKB1 deficient beta cells, expected to greatly diminish insulin secretion via the classic triggering pathway. Thus LKB1 is essential for mitochondrial homeostasis in beta cells and in parallel is a powerful negative regulator of insulin secretion. This study shows that beta cells can be manipulated to enhance GSIS to supra-normal levels even in the face of defective mitochondria and without deterioration over months. PMID- 26139603 TI - Rescue and Stabilization of Acetylcholinesterase in Skeletal Muscle by N-terminal Peptides Derived from the Noncatalytic Subunits. AB - The vast majority of newly synthesized acetylcholinesterase (AChE) molecules do not assemble into catalytically active oligomeric forms and are rapidly degraded intracellularly by the endoplasmic reticulum-associated protein degradation pathway. We have previously shown that AChE in skeletal muscle is regulated in part post-translationally by the availability of the noncatalytic subunit collagen Q, and others have shown that expression of a 17-amino acid N-terminal proline-rich attachment domain of collagen Q is sufficient to promote AChE tetramerization in cells producing AChE. In this study we show that muscle cells, or cell lines expressing AChE catalytic subunits, incubated with synthetic proline-rich attachment domain peptides containing the endoplasmic reticulum retrieval sequence KDEL take up and retrogradely transport them to the endoplasmic reticulum network where they induce assembly of AChE tetramers. The peptides act to enhance AChE folding thereby rescuing them from reticulum degradation. This enhanced folding efficiency occurs in the presence of inhibitors of protein synthesis and in turn increases total cell-associated AChE activity and active tetramer secretion. Pulse-chase studies of isotopically labeled AChE molecules show that the enzyme is rescued from intracellular degradation. These studies provide a mechanistic explanation for the large scale intracellular degradation of AChE previously observed and indicate that simple peptides alone can increase the production and secretion of this critical synaptic enzyme in muscle tissue. PMID- 26139604 TI - Protein Kinase C Phosphorylation of a gamma-Protocadherin C-terminal Lipid Binding Domain Regulates Focal Adhesion Kinase Inhibition and Dendrite Arborization. AB - The gamma-protocadherins (gamma-Pcdhs) are a family of 22 adhesion molecules with multiple critical developmental functions, including the proper formation of dendritic arbors by forebrain neurons. The gamma-Pcdhs bind to and inhibit focal adhesion kinase (FAK) via a constant C-terminal cytoplasmic domain shared by all 22 proteins. In cortical neurons lacking the gamma-Pcdhs, aberrantly high activity of FAK and of PKC disrupts dendrite arborization. Little is known, however, about how gamma-Pcdh function is regulated by other factors. Here we show that PKC phosphorylates a serine residue situated within a phospholipid binding motif at the shared gamma-Pcdh C terminus. Western blots using a novel phospho-specific antibody against this site suggest that a portion of gamma-Pcdh proteins is phosphorylated in the cortex in vivo. We find that PKC phosphorylation disrupts both phospholipid binding and the gamma-Pcdh inhibition of (but not binding to) FAK. Introduction of a non-phosphorylatable (S922A) gamma Pcdh construct into wild-type cortical neurons significantly increases dendrite arborization. This same S922A construct can also rescue dendrite arborization defects in gamma-Pcdh null neurons cell autonomously. Consistent with these data, introduction of a phosphomimetic (S/D) gamma-Pcdh construct or treatment with a PKC activator reduces dendrite arborization in wild-type cortical neurons. Together, these data identify a novel mechanism through which gamma-Pcdh control of a signaling pathway important for dendrite arborization is regulated. PMID- 26139605 TI - Insights into Flavin-based Electron Bifurcation via the NADH-dependent Reduced Ferredoxin:NADP Oxidoreductase Structure. AB - NADH-dependent reduced ferredoxin:NADP oxidoreductase (NfnAB) is found in the cytoplasm of various anaerobic bacteria and archaea. The enzyme reversibly catalyzes the endergonic reduction of ferredoxin with NADPH driven by the exergonic transhydrogenation from NADPH onto NAD(+). Coupling is most probably accomplished via the mechanism of flavin-based electron bifurcation. To understand this process on a structural basis, we heterologously produced the NfnAB complex of Thermotoga maritima in Escherichia coli, provided kinetic evidence for its bifurcating behavior, and determined its x-ray structure in the absence and presence of NADH. The structure of NfnAB reveals an electron transfer route including the FAD (a-FAD), the [2Fe-2S] cluster of NfnA and the FAD (b FAD), and the two [4Fe-4S] clusters of NfnB. Ferredoxin is presumably docked onto NfnB close to the [4Fe-4S] cluster distal to b-FAD. NAD(H) binds to a-FAD and NADP(H) consequently to b-FAD, which is positioned in the center of the NfnAB complex and the site of electron bifurcation. Arg(187) is hydrogen-bonded to N5 and O4 of the bifurcating b-FAD and might play a key role in adjusting a low redox potential of the FADH(*)/FAD pair required for ferredoxin reduction. A mechanism of FAD-coupled electron bifurcation by NfnAB is proposed. PMID- 26139606 TI - Structural Basis for the Interconversion of Maltodextrins by MalQ, the Amylomaltase of Escherichia coli. AB - Amylomaltase MalQ is essential for the metabolism of maltose and maltodextrins in Escherichia coli. It catalyzes transglycosylation/disproportionation reactions in which glycosyl or dextrinyl units are transferred among linear maltodextrins of various lengths. To elucidate the molecular basis of transglycosylation by MalQ, we have determined three crystal structures of this enzyme, i.e. the apo-form, its complex with maltose, and an inhibitor complex with the transition state analog acarviosine-glucose-acarbose, at resolutions down to 2.1 A. MalQ represents the first example of a mesophilic bacterial amylomaltase with known structure and exhibits an N-terminal extension of about 140 residues, in contrast with previously described thermophilic enzymes. This moiety seems unique to amylomaltases from Enterobacteriaceae and folds into two distinct subdomains that associate with different parts of the catalytic core. Intriguingly, the three MalQ crystal structures appear to correspond to distinct states of this enzyme, revealing considerable conformational changes during the catalytic cycle. In particular, the inhibitor complex highlights the requirement of both a 3-OH group and a 4-OH group (or alpha1-4-glycosidic bond) at the acceptor subsite +1 for the catalytically competent orientation of the acid/base catalyst Glu-496. Using an HPLC-based MalQ enzyme assay, we could demonstrate that the equilibrium concentration of maltodextrin products depends on the length of the initial substrate; with increasing numbers of glycosidic bonds, less glucose is formed. Thus, both structural and enzymatic data are consistent with the extremely low hydrolysis rates observed for amylomaltases and underline the importance of MalQ for the metabolism of maltodextrins in E. coli. PMID- 26139607 TI - Activation of Autophagic Flux against Xenoestrogen Bisphenol-A-induced Hippocampal Neurodegeneration via AMP kinase (AMPK)/Mammalian Target of Rapamycin (mTOR) Pathways. AB - The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive. We observed that BPA exposure during the early postnatal period enhanced the expression and the levels of autophagy genes/proteins. BPA treatment in the presence of bafilomycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-LC3-transfected hippocampal neural stem cell-derived neurons. BPA induced generation of reactive oxygen species and apoptosis were mitigated by a pharmacological activator of autophagy (rapamycin). Pharmacological (wortmannin and bafilomycin A1) and genetic (beclin siRNA) inhibition of autophagy aggravated BPA neurotoxicity. Activation of autophagy against BPA resulted in intracellular energy sensor AMP kinase (AMPK) activation, increased phosphorylation of raptor and acetyl-CoA carboxylase, and decreased phosphorylation of ULK1 (Ser-757), and silencing of AMPK exacerbated BPA neurotoxicity. Conversely, BPA exposure down regulated the mammalian target of rapamycin (mTOR) pathway by phosphorylation of raptor as a transient cell's compensatory mechanism to preserve cellular energy pool. Moreover, silencing of mTOR enhanced autophagy, which further alleviated BPA-induced reactive oxygen species generation and apoptosis. BPA-mediated neurotoxicity also resulted in mitochondrial loss, bioenergetic deficits, and increased PARKIN mitochondrial translocation, suggesting enhanced mitophagy. These results suggest implication of autophagy against BPA-mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy, which arbitrates cell survival and demise during stress conditions, requires further assessment to be established as a biomarker of xenoestrogen exposure. PMID- 26139608 TI - Retinylamine Benefits Early Diabetic Retinopathy in Mice. AB - Recent evidence suggests an important role for outer retinal cells in the pathogenesis of diabetic retinopathy (DR). Here we investigated the effect of the visual cycle inhibitor retinylamine (Ret-NH2) on the development of early DR lesions. Wild-type (WT) C57BL/6J mice (male, 2 months old when diabetes was induced) were made diabetic with streptozotocin, and some were given Ret-NH2 once per week. Lecithin-retinol acyltransferase (LRAT)-deficient mice and P23H mutant mice were similarly studied. Mice were euthanized after 2 (WT and Lrat(-/-)) and 8 months (WT) of study to assess vascular histopathology, accumulation of albumin, visual function, and biochemical and physiological abnormalities in the retina. Non-retinal effects of Ret-NH2 were examined in leukocytes treated in vivo. Superoxide generation and expression of inflammatory proteins were significantly increased in retinas of mice diabetic for 2 or 8 months, and the number of degenerate retinal capillaries and accumulation of albumin in neural retina were significantly increased in mice diabetic for 8 months compared with nondiabetic controls. Administration of Ret-NH2 once per week inhibited capillary degeneration and accumulation of albumin in the neural retina, significantly reducing diabetes-induced retinal superoxide and expression of inflammatory proteins. Superoxide generation also was suppressed in Lrat(-/-) diabetic mice. Leukocytes isolated from diabetic mice treated with Ret-NH2 caused significantly less cytotoxicity to retinal endothelial cells ex vivo than did leukocytes from control diabetics. Administration of Ret-NH2 once per week significantly inhibited the pathogenesis of lesions characteristic of early DR in diabetic mice. The visual cycle constitutes a novel target for inhibition of DR. PMID- 26139611 TI - Targeting the Osmotic Stress Response for Strain Improvement of an Industrial Producer of Secondary Metabolites. AB - The transition from primary to secondary metabolism in antibiotic-producing Streptomyces correlates with expression of genes involved in stress responses. Consequently, regulatory pathways that regulate specific stress responses are potential targets to manipulate to increase antibiotic titers. In this study, genes encoding key proteins involved in regulation of the osmotic stress response in Streptomyces avermitilis, the industrial producer of avermectins, are investigated as targets. Disruption of either osaBSa, encoding a response regulator protein, or osaCSa, encoding a multidomain regulator of the alternative sigma factor SigB, led to increased production of both oligomycin, by up to 200%, and avermectin, by up to 37%. The mutations also conditionally affected morphological development; under osmotic stress, the mutants were unable to erect an aerial mycelium. In addition, we demonstrate the delivery of DNA into a streptomycete using biolistics. The data reveal that information on stress regulatory responses can be integrated in rational strain improvement to improve yields of bioactive secondary metabolites. PMID- 26139609 TI - Nicotinic Acetylcholine Receptors Sensitize a MAPK-linked Toxicity Pathway on Prolonged Exposure to beta-Amyloid. AB - Among putative downstream synaptic targets of beta-amyloid (Abeta) are signaling molecules involved in synaptic function, memory formation and cognition, such as the MAP kinases, MKPs, CaMKII, CREB, Fyn, and Tau. Here, we assessed the activation and interaction of signaling pathways upon prolonged exposure to Abeta in model nerve cells expressing nicotinic acetylcholine receptors (nAChRs). Our goal was to characterize the steps underlying sensitization of the nerve cells to neurotoxicity when Abeta-target receptors are present. Of particular focus was the connection of the activated signaling molecules to oxidative stress. Differentiated neuroblastoma cells expressing mouse alpha4beta2-nAChRs were exposed to Abeta1-42 for intervals from 30 min to 3 days. The cells and cell derived protein extracts were then probed for activation of signaling pathway molecules (ERK, JNK, CaMKII, CREB, MARCKS, Fyn, tau). Our results show substantial, progressive activation of ERK in response to nanomolar Abeta exposure, starting at the earliest time point. Increased ERK activation was followed by JNK activation as well as an increased expression of PHF-tau, paralleled by increased levels of reactive oxygen species (ROS). The impact of prolonged Abeta on the levels of pERK, pJNK, and ROS was attenuated by MEK selective and JNK-selective inhibitors. In addition, the MEK inhibitor as well as a JNK inhibitor attenuated Abeta-induced nuclear fragmentation, which followed the changes in ROS levels. These results demonstrate that the presence of nAChRs sensitizes neurons to the neurotoxic action of Abeta through the timed activation of discrete intracellular signaling molecules, suggesting pathways involved in the early stages of Alzheimer disease. PMID- 26139610 TI - Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration. AB - Retinitis pigmentosa, caused predominantly by mutations in photoreceptor genes, currently lacks comprehensive treatment. We discover that retinal microglia contribute non-cell autonomously to rod photoreceptor degeneration by primary phagocytosis of living rods. Using rd10 mice, we found that the initiation of rod degeneration is accompanied by early infiltration of microglia, upregulation of phagocytic molecules in microglia, and presentation of "eat-me" signals on mutated rods. On live-cell imaging, infiltrating microglia interact dynamically with photoreceptors via motile processes and engage in rapid phagocytic engulfment of non-apoptotic rods. Microglial contribution to rod demise is evidenced by morphological and functional amelioration of photoreceptor degeneration following genetic ablation of retinal microglia. Molecular inhibition of microglial phagocytosis using the vitronectin receptor antagonist cRGD also improved morphological and functional parameters of degeneration. Our findings highlight primary microglial phagocytosis as a contributing mechanism underlying cell death in retinitis pigmentosa and implicate microglia as a potential cellular target for therapy. PMID- 26139612 TI - Wolbachia Sequence Typing in Butterflies Using Pyrosequencing. AB - Wolbachia is an obligate symbiotic bacteria that is ubiquitous in arthropods, with 25-70% of insect species estimated to be infected. Wolbachia species can interact with their insect hosts in a mutualistic or parasitic manner. Sequence types (ST) of Wolbachia are determined by multilocus sequence typing (MLST) of housekeeping genes. However, there are some limitations to MLST with respect to the generation of clone libraries and the Sanger sequencing method when a host is infected with multiple STs of Wolbachia. To assess the feasibility of massive parallel sequencing, also known as next-generation sequencing, we used pyrosequencing for sequence typing of Wolbachia in butterflies. We collected three species of butterflies (Eurema hecabe, Eurema laeta, and Tongeia fischeri) common to Korea and screened them for Wolbachia STs. We found that T. fischeri was infected with a single ST of Wolbachia, ST41. In contrast, E. hecabe and E. laeta were each infected with two STs of Wolbachia, ST41 and ST40. Our results clearly demonstrate that pyrosequencing-based MLST has a higher sensitivity than cloning and Sanger sequencing methods for the detection of minor alleles. Considering the high prevalence of infection with multiple Wolbachia STs, next generation sequencing with improved analysis would assist with scaling up approaches to Wolbachia MLST. PMID- 26139613 TI - Optimization of Influencing Factors on Biomass Accumulation and 5-Aminolevulinic Acid (ALA) Yield in Rhodobacter sphaeroides Wastewater Treatment. AB - This study aimed to optimize four factors affecting biomass accumulation and 5 aminolevulinic acid (ALA) yield together with pollutants removal in Rhodobacter sphaeroides wastewater treatment. Results showed that it was feasible to produce biomass and ALA in R. sphaeroides wastewater treatment. Microaerobic, 1,000-3,000 lux, and pH 7.0 were optimal conditions for the highest ALA yield of 4.5 +/- 0.5 mg/g-biomass. Under these conditions, COD removal and biomass production rate were 93.3 +/- 0.9% and 31.8 +/- 0.5 mg/l/h, respectively. In addition, trace elements Fe(2+), Mg(2+), Ni(2+), and Zn(2+) further improved the ALA yield, COD removal, and biomass production rate. Specifically, the highest ALA yield (12.5 +/- 0.6 mg/g-biomass) was achieved with Fe(2+) addition. PMID- 26139615 TI - Domain Characterization of Cyclosporin Regio-Specific Hydroxylases in Rare Actinomycetes. AB - Cytochrome P450 hydroxylase (CYP) in actinomycetes plays an important role in the biosynthesis and bioconversion of various secondary metabolites. Two unique CYPs named CYP-sb21 and CYP-pa1, which were identified from Sebekia benihana and Pseudonocardia autotrophica, respectively, were proven to transfer a hydroxyl group at the 4(th) or 9(th) N-methyl leucine position of immunosuppressive agent cyclosporin A (CsA). Interestingly, these two homologous CYPs showed different CsA regio-selectivities. CYP-sb21 exhibited preferential hydroxylation activity at the 4(th) position over the 9(th) position, whereas CYP-pa1 showed the opposite preference. To narrow down the CYP domain critical for CsA regio selectivity, each CYP was divided into four domains, and each domain was swapped with its counterpart from the other CYP. A total of 18 hybrid CYPs were then individually tested for CsA regioselectivity. Although most of the hybrid CYPs failed to exhibit a significant change in regioselectivity in the context of CsA hydroxylation, hybrid CYP-pa1 swapped with the second domain of CYP-sb21 showed a higher preference for the 9th position. Moreover, hybrid CYPsb21 containing seven amino acids from the 2nd domain of CYP-pa1 showed higher preference for the 4(th) position. These results imply that the 2nd domain of CsA-specific CYP plays a critical role in CsA regio-selectivity, thereby setting the stage for biotechnological application of CsA regio-selective hydroxylation. PMID- 26139614 TI - Combined Effects of Curcumin and (-)-Epigallocatechin Gallate on Inhibition of N Acylhomoserine Lactone-Mediated Biofilm Formation in Wastewater Bacteria from Membrane Bioreactor. AB - This work investigated the potential of curcumin (CCM) and (-)-epigallocatechin gallate (EGCG) to inhibit N-acyl homoserine lactone (AHL)-mediated biofilm formation in gramnegative bacteria from membrane bioreactor (MBR) activated sludge. The minimum inhibitory concentrations (MICs) of CCM alone against all the tested bacteria were 200-350 MUg/ml, whereas those for EGCG were 300-600 MUg/ml. Biofilm formation at one-half MICs indicated that CCM and EGCG alone respectively inhibited 52-68% and 59-78% of biofilm formation among all the tested bacteria. However, their combination resulted in 95-99% of biofilm reduction. Quorum sensing inhibition (QSI) assay with known biosensor strains demonstrated that CCM inhibited the expression of C4 and C6 homoserine lactones (HSLs)-mediated phenotypes, whereas EGCG inhibited C4, C6, and C10 HSLs-based phenotypes. The Center for Disease Control biofilm reactor containing a multispecies culture of nine bacteria with onehalf MIC of CCM (150 MUg/ml) and EGCG (275 MUg/ml) showed 17 and 14 MUg/cm(2) of extracellular polymeric substances (EPS) on polyvinylidene fluoride membrane surface, whereas their combination (100 MUg/ml of each) exhibited much lower EPS content (3 MUg/cm(2)). Confocal laser scanning microscopy observations also illustrated that the combination of compounds tremendously reduced the biofilm thickness. The combined effect of CCM with EGCG clearly reveals for the first time the enhanced inhibition of AHL-mediated biofilm formation in bacteria from activated sludge. Thus, such combined natural QSI approach could be used for the inhibition of membrane biofouling in MBRs treating wastewaters. PMID- 26139616 TI - Large-Scale Refolding and Enzyme Reaction of Human Preproinsulin for Production of Human Insulin. AB - Human insulin is composed of 21 amino acids of an A-chain and 30 amino acids of a B-chain. This is the protein hormone that has the role of blood sugar control. When the recombinant human proinsulin is expressed in Escherichia coli, a serious problem is the formation of an inclusion body. Therefore, the inclusion body must be denatured and refolded under chaotropic agents and suitable reductants. In this study, H27R-proinsulin was refolded from the denatured form with beta mercaptoethanol and urea. The refolding reaction was completed after 15 h at 15 degrees C, whereas the reaction at 25 degrees C was faster than that at 15 degrees C. The refolding yield at 15 degrees C was 17% higher than that at 25 degrees C. The refolding reaction could be carried out at a high protein concentration (2 g/l) using direct refolding without sulfonation. The most economical and optimal refolding condition for human preproinsulin was 1.5 g/l protein, 10 mM glycine buffer containing 0.6 M urea, pH 10.6, and 0.3 mM beta mercaptoethanol at 15 degrees C for 16 h. The maximum refolding yield was 74.8% at 15 degrees C with 1.5 g/l protein. Moreover, the refolded preproinsulin could be converted into normal mature insulin with two enzymes. The average amount of human insulin was 138.2 g from 200 L of fermentation broth after enzyme reaction with H27R-proinsulin. The direct refolding process for H27R-proinsulin was successfully set up without sulfonation. The step yields for refolding and enzyme reaction were comparatively high. Therefore, our refolding process for production of recombinant insulin may be beneficial to the large-scale production of other biologically active proteins. PMID- 26139617 TI - Are French general practitioners consulted before travel to developing countries? A cross-sectional study conducted in a French airport. AB - BACKGROUND: General practitioners (GPs) could play a central role in preventing travel-related health issues. The aim of this study was to assess, in travellers departing to developing countries from a French airport, the proportion of individuals having sought GP counseling before departure and to identify determinants for having consulted a GP. METHODS: Cross-sectional study conducted between November 2012 and July 2013, in all adults living in France. Sociodemographic, health characteristics, type of travel and resources consulted before departure were collected. A descriptive analysis was performed. Determinants for having consulted a GP before departure were investigated using a logistic regression analysis. RESULTS: Of the 360 travellers included, 230 (64%) sought health counseling before departure. GPs were the main source of information for 134 (58%) travellers having sought health information and the only one for 49 (21%). Almost half of the travellers (48%) departing to sub Saharan countries did not seek health counseling from a medical doctor (GP, non GP specialist, specialist consulted in an international vaccination center or occupational physician). Individuals significantly more likely to travel without having consulted a GP were young and male, held foreign nationality, had travelled more than five times before, rarely consulted their GP and were travelling to a non-malarious area. CONCLUSION: GPs were the main but not the only source of information and counseling before traveling to a developing country. This study helps identify the characteristics of individuals likely to travel without having consulted a GP before departure. PMID- 26139618 TI - Rapid consolidation of new knowledge in adulthood via fast mapping. AB - Rapid word learning, where words are 'fast mapped' onto new concepts, may help build vocabulary during childhood. Recent evidence has suggested that fast mapping might help to rapidly integrate information into memory networks of the adult neocortex. The neural basis for this learning by fast mapping determines key properties of the learned information. PMID- 26139619 TI - Clinical characteristics and surgical treatment outcomes of vallecular cysts in adults. AB - CONCLUSION: It is suggested that transoral complete excision is the ideal treatment for adult vallecular cyst to avoid life-threatening acute airway obstruction and disease recurrence. OBJECTIVE: The objective of this study was to review the clinical characteristics and surgical treatment outcomes of vallecular cysts in adults. METHODS: A retrospective chart review was performed at Chonnam National University Hwasun Hospital from January 2009 to December 2014. RESULTS: Nine patients (>= 19-years-of-age) with a vallecular cyst were identified. Most of the patients had minimal or no symptoms at diagnosis. The presence of a vallecular cyst was confirmed in all of the patients by fiberoptic laryngoscopy. All of the cases with a vallecular cyst were treated by the transoral surgical procedure. Recurrence of the vallecular cyst was identified in two (22.2%) patients. One patient had been disease-free after the third operation through the transoral approach. Another patient who underwent marsupialization has been observed without surgery. There were no major complications resulting from surgical intervention. PMID- 26139620 TI - Reply to the Letter to the Editor: Developmental Dislocation of the Hip Successfully Treated by Preoperative Traction and Medial Open Reduction: A 22 year Mean Followup. PMID- 26139621 TI - Editorial Comment: Symposium: Research Advances After a Decade of War. PMID- 26139622 TI - Latissimus Dorsi and Teres Major Transfer With Reverse Shoulder Arthroplasty Restores Active Motion and Reduces Pain for Posterosuperior Cuff Dysfunction. AB - BACKGROUND: In patients with rotator cuff dysfunction, reverse shoulder arthroplasty can restore active forward flexion, but it does not provide a solution for the lack of active external rotation because of infraspinatus and the teres minor dysfunction. A modified L'Episcopo procedure can be performed in the same setting wherein the latissimus dorsi and teres major tendons are transferred to the lateral aspect of proximal humerus in an attempt to restore active external rotation. QUESTIONS/PURPOSES: (1) Do latissimus dorsi and teres major tendon transfers with reverse shoulder arthroplasty improve external rotation function in patients with posterosuperior rotator cuff dysfunction? (2) Do patients experience less pain and have improved outcome scores after surgery? (3) What are the complications associated with reverse shoulder arthroplasty with latissimus dorsi and teres major transfer? METHODS: Between 2007 and 2010, we treated all patients undergoing shoulder arthroplasty who had a profound external rotation lag sign and advanced fatty degeneration of the posterosuperior rotator cuff (infraspinatus plus teres minor) with this approach. A total of 21 patients (mean age 66 years; range, 58-82 years) were treated this way and followed for a minimum of 2 years (range, 26-81 months); none was lost to followup, and all have been seen in the last 5 years. We compared pre- and postoperative ranges of motion, pain, and functional status; scores were drawn from chart review. We also categorized major and minor complications. RESULTS: Active forward flexion improved from 56 degrees +/- 36 degrees to 120 degrees +/- 38 degrees (mean difference: 64 degrees [95% confidence interval {CI}, 45 degrees -83 degrees ], p < 0.001). Active external rotation with the arm adducted improved from 6 degrees +/- 16 degrees to 38 degrees +/- 14 degrees (mean difference: 30 degrees [95% CI, 21 degrees -39 degrees ], p < 0.001); active external rotation with the arm abducted improved from 19 degrees +/- 25 degrees to 74 degrees +/ 22 degrees (mean difference: 44 degrees [95% CI, 22 degrees -65 degrees ], p < 0.001). Pain visual analog score improved from 8.4 +/- 2.3 to 1.7 +/- 2.1 (mean difference: -6.9 [95% CI, -8.7 to -5.2], p < 0.001), and Single Assessment Numeric Evaluation score improved from 28% +/- 21% to 80% +/- 24% (mean difference: 46% [95% CI, 28%-64%], p < 0.001). There were six major complications, five of which were treated operatively. Overall, three patients' latissimus and teres major transfer failed based on persistent lack of external rotation. CONCLUSIONS: In patients with posterior and superior cuff deficiency, reverse shoulder arthroplasty combined with latissimus dorsi and teres major transfer through a single deltopectoral incision can reliably increase active forward flexion and external rotation. Patients experience pain relief and functional improvement but have a high rate of complications; therefore, we recommend the procedure be limited to patients indicated for reverse who have profound external rotation loss and a high grade of infraspinatus/teres minor fatty atrophy. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 26139623 TI - CORR Insights((r)): Does Tourniquet Use in TKA Affect Recovery of Lower Extremity Strength and Function? A Randomized Trial. PMID- 26139624 TI - CORR Insights((r)): The Knee Society Short Form Reduces Respondent Burden in the Assessment of Patient-reported Outcomes. PMID- 26139625 TI - Delirium in the Spanish version of the DSM-5: More confusion? PMID- 26139626 TI - Psychosis, an unusual presentation of Hashimoto's thyroiditis. PMID- 26139627 TI - Erratum. PMID- 26139628 TI - Claudin-1 Binder Enhances Epidermal Permeability in a Human Keratinocyte Model. AB - Tight junctions (TJs) are complex biochemical structures that seal the intercellular space and prevent the free movement of solutes across epithelial cell sheets. Modulating the TJ seal is a promising option for increasing the transdermal absorption of drugs. Within TJs, the binding of the claudin (CLDN) family of tetratransmembrane proteins through cis- and trans-interactions is an integral part of seal formation. Because epidermal TJs contain CLDN-1 and CLDN-4, a binder for these CLDNs may be a useful modulator of the permeability of the epidermal barrier. Here, we investigated whether m19, which can bind to CLDN-1/-4 (also CLDN-2/-5), modulates the integrity of epidermal TJs and the permeability of cell sheets to solutes. Treatment of normal human epidermal keratinocytes (NHEKs) with the CLDN binder reduced the integrity of TJs. A CLDN-1-specific binder (a monoclonal antibody, clone 7A5) also weakened the TJ seal in NHEKs. Although m19 attenuated the TJ barrier in human intestinal epithelial cells (Caco 2), 7A5 did not. Treatment of NHEKs with 7A5 enhanced permeation of a paracellular permeation marker. These findings indicate that CLDN-1 is a potential target for modulating the permeability of the epidermis, and that our CLDN-1 binder is a promising candidate molecule for development as a dermal absorption enhancer. PMID- 26139630 TI - Neutron Scattering Studies of the Effects of Formulating Amphotericin B with Cholesteryl Sulfate on the Drug's Interactions with Phospholipid and Phospholipid Sterol Membranes. AB - Langmuir surface pressure, small-angle neutron scattering (SANS), and neutron reflectivity (NR) studies have been performed to determine how formulation of the antifungal drug amphotericin B (AmB), with sodium cholesteryl sulfate (SCS)-as in Amphotec-affects its interactions with ergosterol-containing (model fungal cell) and cholesterol-containing (model mammalian cell) membranes. The effects of mixing AmB in 1:1 molar ratio with cholesteryl sulfate (yielding AmB-SCS micelles) are compared against those of free AmB, using monolayers and bilayers formed from palmitoyloleoylphosphatidylcholine (POPC) in the absence and presence of 30 mol % ergosterol or cholesterol, in all cases employing a 1:0.05 molar ratio of lipid:AmB. Analyses of the (bilayer) SANS and (monolayer) NR data indicate that the equilibrium changes in membrane structure induced in sterol free and sterol-containing membranes are the same for free AmB and AmB-SCS. Stopped-flow SANS experiments, however, reveal that the structural changes to vesicle membranes occur far more rapidly following exposure to AmB-SCS vs free drug, with the kinetics of these changes varying with membrane composition. With POPC vesicles, the structural changes induced by AmB-SCS become apparent only after several minutes, and equilibrium is reached after ~30 min. The corresponding onset of changes in POPC-ergosterol and POPC-cholesterol vesicles, however, occurs within ~5 s, with equilibrium reached after 10 and 120 s, respectively. The rate of insertion of AmB into POPC-sterol membranes is thus increased through formulation as AmB-SCS. Moreover, the differences in monolayer surface pressure and SANS structure-change equilibration times suggest significant rearrangement of AmB within these membranes following insertion. The reduced times to equilibrium for the POPC-ergosterol vs POPC-cholesterol systems are consistent with the known differences in affinity of AmB for these two sterols, and the reduced time to equilibrium for AmB-SCS interaction with POPC ergosterol membranes vs that for free AmB is consistent with the reduced host toxicity of Amphotec. PMID- 26139629 TI - A national population-based e-cohort of people with psychosis (PsyCymru) linking prospectively ascertained phenotypically rich and genetic data to routinely collected records: overview, recruitment and linkage. AB - PsyCymru was initially established as a proof of concept to investigate the feasibility of linking a prospectively ascertained, well-characterised (linked clinical cohort) of people with psychosis in Wales, UK with large amounts of anonymised routinely collected health record data. We are now additionally linking genetic data. PsyCymru aims to create a research platform and infrastructure for psychosis research in Wales by the establishment of two cohorts. The first is a well characterised clinically-assessed cohort of 490 individuals aged 16 and over, including genetic data. Consented individuals underwent a structured interview using a series of well-validated questionnaires and gave blood for the purpose of DNA extraction for sequencing and candidate gene identification. This data was linked to routinely collected health and social datasets with identity encryption used to protect privacy. The second is a much larger (12,097 individuals) but less well characterised population-based e cohort of prevalent psychosis cases created using a previously validated algorithm applied to anonymised routine data. Both cohorts can be tracked prospectively and retrospectively using anonymised routinely collected electronic health and administrative data in the Secure Anonymised Information Linkage (SAIL) databank. This unique platform pools data together from multiple sources; linking clinical, psychological, biological, genetic and health care factors to address a wide variety of research questions. This resource will continue to expand over the coming years in size, breadth and depth of data, with continued recruitment and additional measures planned. PMID- 26139631 TI - Provider Difficulties With Spiritual and Forgiveness Communication at the End of Life. AB - BACKGROUND: Due to an absence of communication training, provider responses to patient/family spiritual distress are highly variable. Assessing spiritual and forgiveness concerns are important to ensuring quality holistic care. METHODS: Cross-sectional survey data were collected from providers attending 1 of 2 continuing education courses. The survey measured the frequency and initiation of communication about spirituality and forgiveness with patients/families, the perceived difficulty in communication across topics, and preparation and resources for these discussions. RESULTS: Most participants (n = 124) were nurses followed by social workers with over half of providers having 10 years or more of clinical experience. Participants reported the highest level of difficulty in spiritual communication when talking with family after the death of a patient, followed by conducting a spiritual history with a patient. Facilitating forgiveness communication between parent and adult child, followed by facilitating forgiveness between partners was most difficult for all participants. Social workers reported much lower difficulty than nurses on all items of spiritual and forgiveness communication. CONCLUSION: The majority of participants indicated they were involved in spiritual and forgiveness communication. The most difficult communication included talking with family after death and facilitating forgiveness between patients and families. These findings support the importance of spiritual communication in clinical practice, and the need for clinician training in communicating about spirituality and forgiveness with patients and families. PMID- 26139632 TI - Next-generation sequencing in the genomic profiling of synchronous colonic carcinomas: comment on Li et al (2015). PMID- 26139633 TI - A multivariate Bernoulli model to predict DNaseI hypersensitivity status from haplotype data. AB - MOTIVATION: Haplotype models enjoy a wide range of applications in population inference and disease gene discovery. The hidden Markov models traditionally used for haplotypes are hindered by the dubious assumption that dependencies occur only between consecutive pairs of variants. In this article, we apply the multivariate Bernoulli (MVB) distribution to model haplotype data. The MVB distribution relies on interactions among all sets of variants, thus allowing for the detection and exploitation of long-range and higher-order interactions. We discuss penalized estimation and present an efficient algorithm for fitting sparse versions of the MVB distribution to haplotype data. Finally, we showcase the benefits of the MVB model in predicting DNaseI hypersensitivity (DH) status- an epigenetic mark describing chromatin accessibility--from population-scale haplotype data. RESULTS: We fit the MVB model to real data from 59 individuals on whom both haplotypes and DH status in lymphoblastoid cell lines are publicly available. The model allows prediction of DH status from genetic data (prediction R2=0.12 in cross-validations). Comparisons of prediction under the MVB model with prediction under linear regression (best linear unbiased prediction) and logistic regression demonstrate that the MVB model achieves about 10% higher prediction R2 than the two competing methods in empirical data. AVAILABILITY AND IMPLEMENTATION: Software implementing the method described can be downloaded at http://bogdan.bioinformatics.ucla.edu/software/. CONTACT: shihuwenbo@ucla.edu or pasaniuc@ucla.edu. PMID- 26139634 TI - Functional classification of CATH superfamilies: a domain-based approach for protein function annotation. AB - MOTIVATION: Computational approaches that can predict protein functions are essential to bridge the widening function annotation gap especially since <1.0% of all proteins in UniProtKB have been experimentally characterized. We present a domain-based method for protein function classification and prediction of functional sites that exploits functional sub-classification of CATH superfamilies. The superfamilies are sub-classified into functional families (FunFams) using a hierarchical clustering algorithm supervised by a new classification method, FunFHMMer. RESULTS: FunFHMMer generates more functionally coherent groupings of protein sequences than other domain-based protein classifications. This has been validated using known functional information. The conserved positions predicted by the FunFams are also found to be enriched in known functional residues. Moreover, the functional annotations provided by the FunFams are found to be more precise than other domain-based resources. FunFHMMer currently identifies 110,439 FunFams in 2735 superfamilies which can be used to functionally annotate>16 million domain sequences. AVAILABILITY AND IMPLEMENTATION: All FunFam annotation data are made available through the CATH webpages (http://www.cathdb.info). The FunFHMMer webserver (http://www.cathdb.info/search/by_funfhmmer) allows users to submit query sequences for assignment to a CATH FunFam. CONTACT: sayoni.das.12@ucl.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26139635 TI - LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. AB - Assessing linkage disequilibrium (LD) across ancestral populations is a powerful approach for investigating population-specific genetic structure as well as functionally mapping regions of disease susceptibility. Here, we present LDlink, a web-based collection of bioinformatic modules that query single nucleotide polymorphisms (SNPs) in population groups of interest to generate haplotype tables and interactive plots. Modules are designed with an emphasis on ease of use, query flexibility, and interactive visualization of results. Phase 3 haplotype data from the 1000 Genomes Project are referenced for calculating pairwise metrics of LD, searching for proxies in high LD, and enumerating all observed haplotypes. LDlink is tailored for investigators interested in mapping common and uncommon disease susceptibility loci by focusing on output linking correlated alleles and highlighting putative functional variants. AVAILABILITY AND IMPLEMENTATION: LDlink is a free and publically available web tool which can be accessed at http://analysistools.nci.nih.gov/LDlink/. CONTACT: mitchell.machiela@nih.gov. PMID- 26139636 TI - ERGC: an efficient referential genome compression algorithm. AB - MOTIVATION: Genome sequencing has become faster and more affordable. Consequently, the number of available complete genomic sequences is increasing rapidly. As a result, the cost to store, process, analyze and transmit the data is becoming a bottleneck for research and future medical applications. So, the need for devising efficient data compression and data reduction techniques for biological sequencing data is growing by the day. Although there exists a number of standard data compression algorithms, they are not efficient in compressing biological data. These generic algorithms do not exploit some inherent properties of the sequencing data while compressing. To exploit statistical and information theoretic properties of genomic sequences, we need specialized compression algorithms. Five different next-generation sequencing data compression problems have been identified and studied in the literature. We propose a novel algorithm for one of these problems known as reference-based genome compression. RESULTS: We have done extensive experiments using five real sequencing datasets. The results on real genomes show that our proposed algorithm is indeed competitive and performs better than the best known algorithms for this problem. It achieves compression ratios that are better than those of the currently best performing algorithms. The time to compress and decompress the whole genome is also very promising. AVAILABILITY AND IMPLEMENTATION: The implementations are freely available for non-commercial purposes. They can be downloaded from http://engr.uconn.edu/~rajasek/ERGC.zip. CONTACT: rajasek@engr.uconn.edu. PMID- 26139637 TI - Error filtering, pair assembly and error correction for next-generation sequencing reads. AB - MOTIVATION: Next-generation sequencing produces vast amounts of data with errors that are difficult to distinguish from true biological variation when coverage is low. RESULTS: We demonstrate large reductions in error frequencies, especially for high-error-rate reads, by three independent means: (i) filtering reads according to their expected number of errors, (ii) assembling overlapping read pairs and (iii) for amplicon reads, by exploiting unique sequence abundances to perform error correction. We also show that most published paired read assemblers calculate incorrect posterior quality scores. AVAILABILITY AND IMPLEMENTATION: These methods are implemented in the USEARCH package. Binaries are freely available at http://drive5.com/usearch. CONTACT: robert@drive5.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26139638 TI - Acid Suppressive Therapy for Stress Ulcer Prophylaxis in Noncritically Ill Patients. AB - BACKGROUND: The current literature discourages the use of acid suppressive therapy (AST) for stress ulcer prophylaxis (SUP) in noncritically ill patients. However, several sources indicate that the majority of noncritically ill patients are given AST for SUP while there may only be a small proportion of high-risk patients who need SUP therapy. There is a new scoring system to aid practitioners in stratifying the risk of stress ulcer-related gastrointestinal bleeding in noncritically ill patients developed by Herzig et al and appropriately prescribe AST for SUP in this population. OBJECTIVE: Our primary objective was to determine the current usage of AST in noncritically ill patients at a tertiary teaching hospital and use the new scoring system to identify non-intensive care unit patients who were inappropriately given AST. METHODS: We retrospectively determined the percentage of noncritically ill patients who were given AST on medical floors between January 2010 and December 2012. After identifying these patients, we randomly selected a sample and retrospectively collected data from their medical record to determine the gastrointestinal bleeding risk score to determine if the patient was appropriately given AST. RESULTS: Of the 42 600 admissions, 22 949 (53.7%) noncritically ill patients were given AST. A total of 442 patients were randomly selected for data collection and 156 patients were excluded. Gastrointestinal bleeding risk score was calculated in 286 patients. This new risk stratification tool identified 253 (88.5%) patients to have a low (<=7) and low-medium risk score (8-9). CONCLUSIONS: A large percentage of noncritically ill patients were given AST during their hospital stay; 88.5% of these medications were given inappropriately to patients who were at extremely low risk of gastrointestinal bleeding. Using the above information and the AST prescribing patterns at our institution, we estimate a potential inpatient medication cost savings of $114 622 for the study period. PMID- 26139639 TI - Treatment Considerations for Unique Patient Populations With HCV Genotype 1 Infection. AB - OBJECTIVE: To review the literature for the treatment of hepatitis C virus (HCV) genotype 1 in certain populations of patients that require further considerations before therapy initiation. DATA SOURCES: A systematic electronic literature search using the MEDLINE database was performed using the search terms hepatitis C, chronic hepatitis C, drug therapy, end stage liver disease, liver transplantation, HIV, hepatitis B, African Americans, renal insufficiency, obesity, pregnancy, and pediatrics. STUDY SELECTION AND DATA EXTRACTION: English language studies from January 1985 to March 2015 were considered. Additional references were identified from ongoing trials obtained from clinicaltrials.gov, conference proceedings, online databases, and citations in relevant review articles. DATA SELECTION: Direct-acting antivirals are first-line recommendations for the treatment of HCV genotype 1 infection, and these include combinations of sofosbuvir, simeprevir, ledipasvir/sofosbuvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, and ribarvirin. Historical and clinical data focusing on the treatment of HCV with these agents in the following populations were selected: decompensated cirrhosis, post-liver transplant, HIV, African Americans, obesity, hepatitis B coinfection, renal impairment, pregnancy, and pediatrics. CONCLUSION: Depending on the population studied, clinicians must consider differences in efficacy outcomes, potential drug interactions, and adverse effects that patients may experience. PMID- 26139640 TI - Celecoxib Versus Diclofenac in Mild to Moderate Depression Management Among Breast Cancer Patients: A Double-Blind, Placebo-Controlled, Randomized Trial. AB - BACKGROUND: Depression is a well-known complication of breast cancer, which is known to adversely affect quality of life, prognosis, and survival in breast cancer patients. Celecoxib, a nonsteroidal anti-inflammatory drug, which acts via the selective inhibition of cyclo-oxygenase (COX)-2, has been shown to have antidepressive effects. OBJECTIVES: Here, we aimed to compare the efficacy and safety of celecoxib, a selective inhibitor of COX-2, with diclofenac, a nonselective inhibitor of both COX-1 and COX-2 in reducing depressive symptoms and pain in breast cancer patients. METHODS: A total of 52 outpatients with breast cancer with mild to moderate depression, who suffered from pain and needed analgesics, participated in the trial and underwent 6 weeks of treatment with either celecoxib (200 mg twice daily) or diclofenac (50 mg twice daily). Participants were investigated using the Hamilton Depression Rating Scale (HDRS). The primary outcome measure was to compare the antidepressant effects of celecoxib and diclofenac. RESULTS: Repeated-measures analysis demonstrated significant effect for Time * Treatment interaction on the HDRS scores: F(1.76, 87.85) = 9.66; P < 0.001. By study conclusion, greater improvement was observed in the HDRS score of the celecoxib group compared with the diclofenac group (P = 0.002). No one experienced remission (HDRS <= 7) in either group. Frequencies of adverse events were not significantly different between groups. CONCLUSION: Celecoxib seems to possess superior antidepressive effects compared with diclofenac in breast cancer patients with mild to moderate depression. PMID- 26139641 TI - Liver enzymes and incident diabetes in China: a prospective analysis of 10 764 participants in the Guangzhou Biobank Cohort Study. AB - BACKGROUND: Impaired liver function has been shown to be associated with incident diabetes. The independent role of the different liver enzymes, including gamma glutamyltransferase (GGT), alanine transaminase (ALT) and aspartate transaminase (AST), has not been addressed properly, taking into account their high collinearity. We used partial least squares (PLS) regression to identify the contribution of ALT, AST and GGT, which appears causally associated with diabetes as a validation factor, to incident diabetes in a South China population where liver impairment and diabetes are common. METHODS: Participants were from the Guangzhou Biobank Cohort Study recruited in 2003-2008, with follow-up re examination up to the end of 2012. Multivariable generalised linear models and PLS were used to examine the adjusted associations of ALT, AST and GGT with diabetes. Incident diabetes was defined as self-reported diabetes, and/or initiation of hypoglycaemia medication or insulin during follow-up, or fasting glucose >=7.0 mmol/L, or 2 h oral glucose tolerance test, glucose >=11.1 mmol/L at follow-up examination. RESULTS: In 10 764 Chinese participants aged >=50 years with no diabetes at baseline, 1228 (11.4%) developed diabetes during the median 4 years of follow-up. Using PLS, the risk for incident diabetes was higher by 18% (95% CI 8% to 27%) per 1 SD increment in log-ALT, and expectedly higher by 36% (95% CI 26% to 52%) for log-GGT, adjusted for age, sex, education, smoking, alcohol, physical activity, waist circumference and body mass index. Similarly adjusted, no association for log-AST (relative risk 0.92, 95% CI 0.85 to 1.01) was found. CONCLUSIONS: ALT but not AST was associated with incident diabetes. Further experimental studies are needed to confirm the causal association and clarify the underlying mechanisms. PMID- 26139642 TI - Sickness absence and the time-varying excess risk of premature death: a Swedish population-based prospective cohort study. AB - BACKGROUND: Previous studies have found that sickness absentees have an excess risk of premature death. Most of the studies compared sickness absentees with non sickness absentees, with 1 report including the total population. However, no study to date has investigated in detail how the risk of premature death varies over the time course of a sick-leave spell. METHODS: A population-based cohort of all 5.6 million people aged 16-64 years was followed up for 6 years. Hazard rates with 95% CI for mortality in the total population, sickness absentees with sick leave spells exceeding 30 days and non-sickness absentees, were estimated over time and were standardised so that the distribution of background variables in all 3 groups was as close as possible to that in the total population. RESULTS: The standardised hazard rate of premature death at the first day under risk for the sickness absentees was 13.58 (95% CI 13.26 to 13.95) deaths per 1000 person years, 2.29 (2.24 to 2.35) in the total population and 0.90 (0.87 to 0.94) among non-sickness absentees. The standardised hazard rates of premature death at 6 years was 3.42 (3.22 to 3.62) among sickness absentees, 3.48 (3.43 to 3.52) in the total population and 2.61 (2.57 to 2.66) among the non-sickness absentees. The hazard rates varied greatly across sick-leave diagnoses. CONCLUSIONS: Right after start of a sick-leave spell exceeding 30 days, sickness absentees were at higher risk of premature death than the total population. The difference in risk, however, decreased over time and vanished completely after 6 years of follow-up. PMID- 26139643 TI - Too late to back out? Options for breech presentation management. PMID- 26139644 TI - Role of exploratory laparoscopy in haemodynamically stable patient with a penetrating abdominal trauma. AB - A young lady presented to the hospital following a penetrating abdominal trauma. She was haemodynamically stable during the initial assessment. Despite fruitless finding from blood test, plain radiograph and computed tomographic scanning, a bowel contusion was found during an explorative laparoscopy. Here, we highlight the need for laparoscopy as a diagnostic and therapeutic tool in haemodynamically stable patient with a penetrating abdominal trauma. PMID- 26139645 TI - The Otalgia Point: A Novel Clinical Gesture in Otolaryngology. AB - INTRODUCTION: In cases of otalgia without any accompanying findings, some patients locate their otalgia below the attachment of the lobule, at the apex of the jugulodigastric region. PURPOSE: To present a series of these patients for whom nasal steroids or myringotomy usually ameliorated their pain. MATERIALS AND METHODS: Thirty-two patients with normal physical examinations, tympanograms, and age-appropriate audiograms spontaneously indicated otalgia at "the otalgia point." Inspection of the oropharynx and nasal airway, palpation of the neck and temporal mandibular joints, and nasopharyngoscopy/laryngoscopy ruled out referred causes of otalgia. Patients were offered either nasal steroid spray or trial myringotomy followed by tympanostomy tube. RESULTS: Otalgia improved in all 10 (100%) patients who selected nasal steroids. Otalgia resolved in 17 of 20 (85%) myringotomy participants. Three patients declined intervention. In all, symptoms improved in 27/29 treated patients (93%). CONCLUSION: This description of "the otalgia point" introduces a new otolaryngologic gesture in physical examination that can aid in the therapeutic management of some patients with otalgia and normal examinations. This is an uncontrolled case series that serves as a pilot study for further exploration of this gesture. PMID- 26139646 TI - Pontine abscess with initial treatment failure following infectious endocarditis with Streptococcus salivarius. AB - We present a case report of a 65-year-old man admitted to the department of infectious diseases on suspicion of meningitis with headache, fever and double vision. A cerebral MRI revealed a 17*30 mm pontine abscess with surrounding oedema. The patient had, 2 months prior to admission, been treated for Streptococcus salivarius aortic valve endocarditis. The abscess was not suitable for surgery, and the patient received multidrug antibiotic treatment for 4 weeks. The patient initially responded well clinically, but was readmitted 4 weeks after discontinuation of treatment, with headache and dizziness. A new cerebral MRI showed progression of the abscess. He received an additional 8 weeks of broad spectrum antibiotic treatment, followed by 12 weeks of oral treatment with pivampicillin. His symptoms resolved and a cerebral MRI at discontinuation of treatment showed regression of the abscess to 7.5 mm. PMID- 26139647 TI - An adolescent with hereditary spherocytosis who presented with splenic infarction. AB - A 16-year-old male patient with known hereditary spherocytosis presented with a 4 day history of chest pain and lethargy. On admission, he had a low-grade fever and was grossly anaemic; examination revealed splenomegaly. An ultrasound scan confirmed splenomegaly with areas of splenic infarction. Subsequent tests suggested possible Epstein-Barr virus infection. The patient recovered well and had a functional spleen on discharge. This case report presents an unusual complication of isolated hereditary spherocytosis. PMID- 26139648 TI - Postnatal acute renal failure after fetal exposure to angiotensin receptor blockers. AB - Maternal hypertensive treatment with angiotensin receptor blockers (ARBs) during the second and third trimester of pregnancy is associated with several fetal and neonatal complications, and potential adverse outcomes. We report a neonate presenting with transient renal acute failure during the first days of life after maternal treatment with ARBs. Women who became pregnant while taking one of these drugs must modify antihypertensive therapy with a different class drug as soon as pregnancy is recognised. PMID- 26139649 TI - Association of coronary to left ventricular microfistulae (vessels of Wearn) with atrial septal defect in an adult without cyanotic heart disease. AB - Vessels of Wearn are rare findings during coronary angiography in adults. They are known to be associated with forms of cyanotic congenital heart disease in infants but we are not aware of any published cases of association with non cyanotic left to right shunts in adults. We present the case of a 69-year-old man with angiographically evident vessels of Wearn draining from the left and right coronary arteries into the left ventricle associated with an asymptomatic atrial septal defect. We postulate a developmental phase association between atrial septal maturation and closure of perfusing microchannels from the ventricular cavities to the epicardial coronary arteries on the same spectrum as that which leads to more widespread defects in infants. We also highlight a common medication side effect that might have been mistaken as a manifestation of the congenital anomalies. PMID- 26139650 TI - Floppy eyelid syndrome. PMID- 26139651 TI - Hypertrophic olivary degeneration secondary to traumatic brain injury: a unique form of trans-synaptic degeneration. PMID- 26139652 TI - Crystals seen on CSF microscopy in a case of suspected subarachnoid haemorrhage. AB - Although crystals are rarely identified on cerebrospinal fluid (CSF) microscopy, their presence can be of significant diagnostic value. We report a case of oxalate crystals seen on CSF microscopy of a 43-year-old woman. The patient presented with headaches, nausea and vomiting. CT of the head showed a small focus of hyper-density, suspicious of haemorrhage, in the right side of the pontine cistern. CSF cell count was within the normal range. Although no organisms were seen on microscopy, copious oxalate crystals were seen. The same crystals were seen on microscopy of CSF collected in a fluoride oxalate container used for glucose analysis. A follow-up contrast-enhanced CT angiogram did not demonstrate any abnormalities. It transpired that excess CSF had been collected into a fluoride oxalate container. This had subsequently been decanted into a plain container for microbiological analysis. Correct specimen collection should be emphasised when teaching lumbar puncture technique. PMID- 26139653 TI - Status postpneumonectomy for pulmonary artery sarcoma. AB - Primary pulmonary artery sarcoma is a rare disease that has a poor survival prognosis due to misdiagnosis with pulmonary thromboembolism or metastatic embolisation, detailed image findings and complicated surgical procedures. Surgical procedures established for treatment include pneumonectomy and pulmonary endarterectomy. Survival after surgery still remains at 1 year survival of 50%. The following case report demonstrates a patient's status postpneumonectomy for pulmonary artery sarcoma that presented with no complications after 1.5-year follow-up. PMID- 26139654 TI - Intercostal neuralgia as a symptom of an osteoblastoma in thoracic spine. AB - An osteoblastoma is a benign bone lesion most commonly affecting the spine; it is frequently found in the posterior elements of the vertebra. When an osteoblastoma originates in the spine, it usually causes dull and localised dorsal pain, but the period between symptom development and diagnosis can be long. MRI shows intense peritumoural oedema accompanying the osteoblastoma. We present a case of a 15-year-old boy with osteoblastoma at the level of the T8-9 left laminae causing intercostal neuralgia without direct invasion to the intercostal nerve. Immediately after surgery, intercostal neuralgia was diminished. To our knowledge, this is the first case of an osteoblastoma with intercostal neuralgia, which is possibly the key symptom for diagnosing an osteoblastoma in the thoracic spine. PMID- 26139655 TI - Validation of statistical shape modelling to predict hip osteoarthritis in females: data from two prospective cohort studies (Cohort Hip and Cohort Knee and Chingford). AB - OBJECTIVES: To prospectively investigate whether hip shape variants at baseline are associated with the need for future total hip replacement (THR) in women and to validate the resulting associated shape variants of the Cohort Hip and Cohort Knee (CHECK) cohort and the Chingford cohort. METHODS: Female participants from the CHECK cohort without radiographic OA (Kellgren-Lawrence score <2) at baseline were included (1100 hips); 22 hips had a THR within 5 years of follow-up. For the Chingford cohort, with only female participants, hips without radiographic OA at baseline were selected and a nested case-control design was used, with 19 THR cases within 19 years of follow-up and 95 controls matched 5 to 1 for age and BMI. Hip shape on baseline anteroposterior pelvic radiographs was assessed by statistical shape modelling (SSM) using the same model for both cohorts. RESULTS: In the CHECK and Chingford cohorts, the respective mean age was 55.8 (s.d. 5.1) and 53.6 (s.d. 5.4) and the BMI was 26.14 (s.d. 4.3) and 25.7 (s.d. 3.3), respectively. Multiple shape variants of the hip were significantly (P < 0.05) associated with future THR in both the CHECK (modes 4, 11, 15, 17 and 22) and Chingford (modes 2 and 17) cohorts. Mode 17 [odds ratio (OR) 0.51 (95% CI 0.33, 0.80) in the CHECK cohort], representing a flattened head-neck junction and flat greater trochanter, could be confirmed in the Chingford cohort [OR 0.41 (95% CI 0.23, 0.82)]. Modes 4 and 15 of the CHECK cohort also showed non-significant trends in the Chingford cohort. CONCLUSION: Several baseline shape variants are associated with the future need for THR within a cohort. Despite differences in participant characteristics, radiographic protocol and follow-up time, we could validate at least one shape variant, suggesting that SSM is reasonably transferable between cohorts. PMID- 26139656 TI - Treatment failure by canakinumab in a patient with progressive multisystemic Erdheim-Chester disease refractory to anakinra: successful use of vemurafenib. PMID- 26139657 TI - Methotrexate for maintenance of remission in IgG4-related disease. PMID- 26139658 TI - Decision making and preferences for acoustic signals in choice situations by female crickets. AB - Multiple attributes usually have to be assessed when choosing a mate. Efficient choice of the best mate is complicated if the available cues are not positively correlated, as is often the case during acoustic communication. Because of varying distances of signalers, a female may be confronted with signals of diverse quality at different intensities. Here, we examined how available cues are weighted for a decision by female crickets. Two songs with different temporal patterns and/or sound intensities were presented in a choice paradigm and compared with female responses from a no-choice test. When both patterns were presented at equal intensity, preference functions became wider in choice situations compared with a no-choice paradigm. When the stimuli in two-choice tests were presented at different intensities, this effect was counteracted as preference functions became narrower compared with choice tests using stimuli of equal intensity. The weighting of intensity differences depended on pattern quality and was therefore non-linear. A simple computational model based on pattern and intensity cues reliably predicted female decisions. A comparison of processing schemes suggested that the computations for pattern recognition and directionality are performed in a network with parallel topology. However, the computational flow of information corresponded to serial processing. PMID- 26139659 TI - Serotonin, but not dopamine, controls the stress response and anxiety-like behavior in the crayfish Procambarus clarkii. AB - In the animal kingdom, biogenic amines are widespread modulators of the nervous system that frequently interact to control mood. Our previous investigations in crayfish (Procambarus clarkii) have established that stress induces changes in brain serotonin (5-HT) concentrations that are responsible for the appearance of anxiety-like behavior (ALB). Here, we further analyze the roles of 5-HT and another biogenic amine, dopamine (DA), on the crayfish response to stress. We show that the intensity of crayfish ALB depends on the intensity of stressful stimulation and is associated with increased concentrations of 5-HT in the brain. These 5-HT levels were significantly correlated, before, as well as after stress, with those of DA, which were approximately 3- to 5-times less abundant. However, whereas the degree of ALB was clearly correlated with brain 5-HT concentrations, it was not significantly correlated with DA. Moreover, in contrast to injections of 5-HT, DA injections were not able to elicit a stress response or ALB. In addition, 5-HT and DA levels were not modified by treatment with the anxiolytic chlordiazepoxide, confirming that suppression of ALB by this GABA-A receptor ligand acts downstream and is independent of changes in crayfish bioamine levels. Our study also provides evidence that the anxiogenic effect of 5-HT injections can be prevented by a preliminary injection of 5-HT antagonists. Altogether, our results emphasize that the rises in brain concentrations of 5-HT, but not DA, play a role in controlling the induction and the intensity of crayfish ALB. PMID- 26139660 TI - Finite element modeling of occlusal variation in durophagous tooth systems. AB - In addition to breaking hard prey items, the teeth of durophagous predators must also resist failure under high loads. To understand the effects of morphology on tooth resistance to failure, finite element models were used to examine differences in total strain energy (J), first principal strain and the distribution of strains in a diversity of canonical durophagous tooth morphologies. By changing the way loads were applied to the models, I was also able to model the effects of large and small prey items. Tooth models with overall convex morphologies have higher in-model strains than those with a flat or concave occlusal surface. When a cusp is added to the tooth model, taller or thinner cusps increase in-model strain. While there is little difference in the relationships between tooth morphology and strain measurements for most models, there is a marked difference between effects of the large and small prey loads on the concave and flat tooth morphologies. Comparing these data with measurements of force required by these same morphologies to break prey items illustrates functional trade-offs between the need to prevent tooth failure under high loads by minimizing in-tooth strain versus the drive to reduce the total applied force. PMID- 26139661 TI - Oculomotor strategy of an avian ground forager: tilted and weakly yoked eye saccades. AB - Many bird species are capable of large saccadic eye movements that can result in substantial shifts in gaze direction and complex changes to their visual field orientation. In the absence of visual stimuli, birds make spontaneous saccades that follow an endogenous oculomotor strategy. We used new eye-tracking technology specialized for small birds to study the oculomotor behavior of an open-habitat, ground-foraging songbird, the European starling (Sturnus vulgaris). We found that starlings primarily move their eyes along a tilted axis 13.46 deg downwards anteriorly and upwards posteriorly, which differs from the axis parallel to the horizon employed by other species. This tilted axis could enhance foraging and anti-predator strategies while starlings are head-down looking for food, allowing them to direct vision between the open mandibles to visually inspect food items, and above and behind the head to scan areas where predators are more likely to attack. We also found that starlings have neither fully conjugate saccades (as in humans, for example) nor independent saccades (as in chameleons, for example). Rather, they exhibit weakly yoked saccades where the left and right eyes move at the same time but not at the same magnitude. Functionally, weakly yoked saccades may be similar to independent saccades in that they allow the two eyes to concomitantly perform different tasks. The differences between the oculomotor strategies of studied species suggest eye movements play variable but important roles across bird species with different ecological niches. PMID- 26139662 TI - Food restriction negatively affects multiple levels of the reproductive axis in male house finches, Haemorhous mexicanus. AB - Nutrition influences reproductive functions across vertebrates, but the effects of food availability on the functioning of the hypothalamic-pituitary-gonadal (HPG) axis in wild birds and the mechanisms mediating these effects remain unclear. We investigated the influence of chronic food restriction on the HPG axis of photostimulated house finches, Haemorhous mexicanus. Food-restricted birds had underdeveloped testes with smaller seminiferous tubules than ad libitum fed birds. Baseline plasma testosterone increased in response to photostimulation in ad libitum-fed but not in food-restricted birds. Food availability did not, however, affect the plasma testosterone increase resulting from a gonadotropin releasing hormone-I (GnRH) or a luteinizing hormone (LH) challenge. The number of hypothalamic GnRH immunoreactive (ir) but not proGnRH-ir perikarya was higher in food-restricted than in ad libitum-fed finches, suggesting inhibited secretion of GnRH. Hypothalamic gonadotropin-inhibitory hormone (GnIH)-ir and neuropeptide Y (NPY)-ir were not affected by food availability. Plasma corticosterone (CORT) was also not affected by food availability, indicating that the observed HPG axis inhibition did not result from increased activity of the hypothalamic-pituitary adrenal (HPA) axis. This study is among the first to examine multilevel functional changes in the HPG axis in response to food restriction in a wild bird. The results indicate that food availability affects both hypothalamic and gonadal function, but further investigations are needed to clarify the mechanisms by which nutritional signals mediate these effects. PMID- 26139663 TI - Drift dives and prolonged surfacing periods in Baikal seals: resting strategies in open waters? AB - Many pinnipeds frequently rest on land or ice, but some species remain in open waters for weeks or months, raising the question of how they rest. A unique type of dive, called drift dives, has been reported for several pinnipeds with suggested functions of rest, food processing and predator avoidance. Prolonged surfacing periods have also been observed in captive seals and are thought to aid food processing. However, information from other species in a different environment would be required to better understand the nature and function of this behavior. In this study, we attached multi-sensor tags to Baikal seals Pusa sibirica, a rare, freshwater species that has no aquatic predators and few resting grounds during the ice-free season. The seals exhibited repeated drift dives (mean depth, 116 m; duration, 10.1 min) in the daytime and prolonged periods at the surface (mean duration, 1.3 h) mainly around dawn. Drift dives and prolonged surfacing periods were temporally associated and observed between a series of foraging dives, suggesting a similar function, i.e. a combination of resting and food processing. The maximum durations of both drift and foraging dives were 15.4 min, close to the aerobic dive limit of this species; therefore, metabolic rates might not be significantly depressed during drift dives, further supporting the function of food processing rather than purely resting. Our results also show that drift diving can occur in a predator-free environment, and thus predator avoidance is not a general explanation of drift dives in pinnipeds. PMID- 26139664 TI - Union expresses concern about plans to close surveillance centre. PMID- 26139665 TI - 'Helpful and constructive' feedback. PMID- 26139666 TI - BBSRC sets out its vision for veterinary vaccinology. PMID- 26139667 TI - New veterinary science centre officially opens in Wales. PMID- 26139668 TI - BSE case in Ireland confirmed as an isolated case of classical BSE. PMID- 26139669 TI - Henry Schein to acquire a majority interest in Kruuse. PMID- 26139670 TI - 'Veterinary Vision' essay competition. PMID- 26139671 TI - Northern Ireland moves to biennial brucellosis testing. PMID- 26139672 TI - 'Hennovation project' aims to find new ways to improve hen welfare. PMID- 26139673 TI - Company advocates sustainable production of affordable protein. PMID- 26139674 TI - Veterinary medicines: product update. AB - The following information has been produced for Veterinary Record by the Veterinary Medicines Directorate (VMD) to provide an update for veterinary surgeons on recent changes to marketing authorisations for veterinary medicines in the UK and on other relevant issues. PMID- 26139675 TI - Challenges and changes in continuing professional development. PMID- 26139676 TI - Prophylactic use of antimicrobials in surgical pig models; a literature review (2012-2014). AB - There are no guidelines for antimicrobial use in experimental animals even though appropriate selection is required to reduce risk of surgical site infection (SSI) and resistance development. Pigs are used extensively as experimental surgical models for people. This review compares reported antimicrobial prescription in recently published pig surgical studies (retrieved by PubMed, Web of Knowledge and Google Scholar) with human guidelines for prophylactic antimicrobial use (National Institute of Clinical Excellence and the American Society of Health System Pharmacists). A five-point appropriate antimicrobial use index (AAUI), based on aforementioned guidelines, was used to grade 233 studies. Use of World Health Organization-designated critically important antimicrobials (CIA) was recorded. Antimicrobial use was described in 111 of 233 (48 per cent) papers. AAUI scores of 5 (maximal compliance) and 0 (no compliance) were awarded to 34 (15 per cent) and 101 (43 per cent) articles. Where reported, prophylactic antimicrobials were mostly administered after surgery (62/95, 65 per cent) and intramuscularly (36/72, 50 per cent). CIAs were described in 21 of 111 (19 per cent) papers and SSIs in 21 of 233 (9 per cent). Reported antimicrobial prophylaxis in experimental pig surgery deviates from human clinical guidelines. This has implications for antimicrobial resistance, study quality and animal welfare. Until species-specific guidelines are formulated, experimental surgical studies involving animals would probably benefit from adherence to human guidelines. PMID- 26139677 TI - Intercurrent tickborne fever infection and Bibersteinia trehalosi septicaemia in a five-week-old lamb. PMID- 26139678 TI - Controlling Cryptosporidium. PMID- 26139679 TI - Primary health care. PMID- 26139688 TI - Following dreams, having adventures. AB - Paula Grant works with beef and sheep in New Zealand, using the experience she gained as a vet on the Isle of Islay, and as a farmer in France. PMID- 26139689 TI - Endovascular stenting in the management of malignant superior vena cava obstruction: comparing safety, effectiveness, and outcomes between primary stenting and salvage stenting. AB - OBJECTIVE: To compare the safety, effectiveness, and outcomes of primary stenting and salvage stenting for malignant superior vena cava obstruction. DESIGN: Case series with internal comparison. SETTING: Regional hospital, Hong Kong. PATIENTS: A total of 56 patients with malignant superior vena cava obstruction underwent 59 stentings from 1 May 1999 to 31 January 2014. Patients' characteristics, procedural details, and outcomes were retrospectively reviewed. Of the 56 patients, 33 had primary stenting before conventional therapy and 23 had salvage stenting after failure of conventional therapy. Statistical analyses were made by Fisher's exact test and Mann-Whitney U test. RESULTS: Primary lung carcinoma was the most common cause of malignant superior vena cava obstruction (primary stenting, 22 patients; salvage stenting, 16 patients; P=0.768), followed by metastatic lymphadenopathy. Most patients had superior vena cava obstruction only (primary stenting, 16 patients; salvage stenting, 15 patients; P=0.633), followed by additional right brachiocephalic vein involvement. Wallstents (Boston Scientific, Natick [MA], US) were used in all patients. Technical success was achieved in all but two patients, one in each group (P=1.000). Only one stent placement was required in most patients (primary stenting, 28 patients; salvage stenting, 20 patients; P=0.726). Procedure time was comparable in both groups (mean time: primary stenting, 89 minutes; salvage stenting, 84 minutes; P=0.526). Symptomatic relief was achieved in most patients (primary stenting, 32 patients; salvage stenting, 23 patients; P=0.639). In-stent restenosis and bleeding were the commonest complications (primary stenting, 6 and 1 patients, respectively; salvage stenting, 2 and 2 patients, respectively). Nine patients required further treatment for symptom recurrence (primary stenting, 6 patients; salvage stenting, 3 patients; P=0.725). CONCLUSION: Endovascular stenting is safe and effective for relieving malignant superior vena cava obstruction. No statistically significant differences in number of stents, success rates, procedure times, symptom relief rates, complication rates, and re-procedure rates were found between primary stenting and salvage stenting. PMID- 26139690 TI - Is locking plate fixation a better option than casting for distal radius fracture in elderly people? AB - OBJECTIVES: To compare the outcomes of locking plate fixation versus casting for displaced distal radius fracture with unstable fracture pattern in active Chinese elderly people. DESIGN: Historical cohort study. SETTING: Orthopaedic ward and clinic at Tseung Kwan O Hospital, Hong Kong. PATIENTS: Between 1 May 2010 and 31 October 2013, 57 Chinese elderly people aged 61 to 80 years were treated either operatively with locking plate fixation (n=26) or conservatively with cast immobilisation (n=31) for unstable displaced distal radius fracture. MAIN OUTCOME MEASURES: Clinical, radiological, and functional outcomes were assessed at 9 to 12 months after treatment. RESULTS: The functional outcome (based on the quick Disabilities of the Arm, Shoulder and Hand score) was significantly better in the locking plate fixation group than in the cast immobilisation group, while clinical and radiological outcomes were comparable with those in other similar studies. CONCLUSIONS: Locking plate fixation resulted in better functional outcome for displaced distal radius fracture with unstable fracture pattern in active Chinese elderly people aged 61 to 80 years. Further prospective study with long-term follow-up is recommended. PMID- 26139691 TI - Computer simulations of glasses: the potential energy landscape. AB - We review the current state of research on glasses, discussing the theoretical background and computational models employed to describe them. This article focuses on the use of the potential energy landscape (PEL) paradigm to account for the phenomenology of glassy systems, and the way in which it can be applied in simulations and the interpretation of their results. This article provides a broad overview of the rich phenomenology of glasses, followed by a summary of the theoretical frameworks developed to describe this phenomonology. We discuss the background of the PEL in detail, the onerous task of how to generate computer models of glasses, various methods of analysing numerical simulations, and the literature on the most commonly used model systems. Finally, we tackle the problem of how to distinguish a good glass former from a good crystal former from an analysis of the PEL. In summarising the state of the potential energy landscape picture, we develop the foundations for new theoretical methods that allow the ab initio prediction of the glass-forming ability of new materials by analysis of the PEL. PMID- 26139692 TI - Nanoscale patterns formed by ion bombardment of rotating binary materials. AB - We explore the effects of sample rotation during ion sputtering of binary materials, as well as its effects during surfactant sputtering. We find that the rate with which the surface roughens or smooths depends on the period of rotation t(0) in the early time regime, in contrast to the behavior of elemental materials. In addition, the characteristic length scale l of the patterns that emerge can be tuned merely by changing the value of t(0). Finally, we demonstrate that l can even exhibit a jump discontinuity as t(0) is varied. PMID- 26139693 TI - A Moral Panic? The Problematization of Forced Marriage in British Newspapers. AB - This article examines the British media's construction of forced marriage (FM) as an urgent social problem in a context where other forms of violence against women are not similarly problematized. A detailed analysis of four British newspapers over a 10-year period demonstrates that media reporting of FM constitutes a moral panic in that it is constructed as a cultural problem that threatens Britain's social order rather than as a specific form of violence against women. Thus, the current problematization of FM restricts discursive spaces for policy debates and hinders attempts to respond to this problem as part of broader efforts to tackle violence against women. PMID- 26139694 TI - Violence as an Under-Recognized Barrier to Women's Realization of Their Right to Adequate Food and Nutrition: Case Studies From Georgia and South Africa. AB - This article addresses under-acknowledged barriers of structural violence and discrimination that interfere with women's capacity to realize their human rights generally, and their right to adequate food and nutrition in particular. Case studies from Georgia and South Africa illustrate the need for a human rights based approach to food and nutrition security that prioritizes non discrimination, public participation, and self-determination. These principles are frustrated by different types of structural violence that, if not seriously addressed, pose multiple barriers to women's economic, public, and social engagement. PMID- 26139695 TI - Exchange and electric fields enhanced spin thermoelectric performance of germanene nano-ribbon. AB - The spin thermoelectric performance in a germanene nano-ribbon is studied by using the nonequilibrium Green's function method. We demonstrate theoretically that the temperature bias [Formula: see text] can generate spin thermopower when an exchange field breaks the edge states of germanene leads. However, the spin thermoelectric efficiency is quite low with its maximum [Formula: see text]. When applying strong electric field in the central region, a relatively large spin dependent band gap can be opened, and hence the spin figure of merit is predicted to be more than 100 times larger than the case without external field. The remarkably enhancement of [Formula: see text] (larger than one) comes from the suppression of the thermal conductance and the improvement of the spin Seebeck effect. These striking properties make ferromagnetic leads germanene nano-ribbon a promising pure spin thermoelectric nanogenerator. PMID- 26139696 TI - Gate controlled resonant widths in double-bend waveguides: bound states in the continuum. AB - We consider quantum transmission through double-bend [Formula: see text]- and Z shaped waveguides controlled by the finger gate potential. Using the effective non-Hermitian Hamiltonian approach we explain the resonances in transmission. We show a difference in transmission in the short waveguides that is the result of different chirality in Z and [Formula: see text] waveguides. We demonstrate that the potential selectively affects the resonant widths resulting in the occurrence of bound states in the continuum. PMID- 26139697 TI - What happens to episode duration and cycle length over the course of bipolar disorder? AB - OBJECTIVES: Published scientific literature on cycle acceleration over the course of bipolar disorder has been equivocal. The present analysis aimed to find whether episode duration and cycle lengths become shorter over the course of bipolar disorder with predominantly manic polarity. METHODS: The present study comprised 150 patients diagnosed with bipolar I disorder using SCID-I for DSM-IV TR. The course of illness was charted according to the NIMH Life Chart Methodology - Clinician Retrospective Chart (NIMH - LCM CRC). Spearman correlation was used to assess the relationship of episode duration and cycle length with the number of episodes. RESULTS: The mean age of the sample was 37.8 years and the average duration of illness was 13.4 years. Unipolar mania comprised 52.7% of the sample. The episode duration and the cycle length decreased with increasing number of episodes (r=-0.245, p<0.001 & r=-0.299, p<0.001 respectively). CONCLUSION: The present study suggests that over the course of bipolar I disorder, cycle length and episode duration become shorter. PMID- 26139698 TI - Implementing evidence-based physical activity interventions for people with mental illness: an Australian perspective. AB - OBJECTIVES: Physical activity (PA) and exercise is increasingly being recognised as an efficacious component of treatment for various mental disorders. The association between PA and cardiometabolic disease is well established, as is the strong link between mental illness, sedentary behaviour and poor cardiometabolic health. Examples of successful integration of clinical PA programs within mental health treatment facilities are increasing. The aim of this review was to summarise the evidence regarding PA and mental illness, and to present examples of clinical exercise programs within Australian mental health facilities. METHODS: A narrative synthesis of systematic reviews and clinical trials was conducted. RESULTS: Evidence supporting the inclusion of PA programs as an adjunct to treatment for various conditions was presented; including depression, schizophrenia, anxiety disorders, post-traumatic stress disorder and substance abuse. In light of the available evidence, the inclusion of clinical PA programs within mental health treatment, facilitated by dedicated clinicians (exercise physiologists / physiotherapists) was justified. CONCLUSIONS: PA is a feasible, effective and acceptable adjunct to usual care for a variety of mental disorders. There is a clear need for greater investment in initiatives aiming to increase PA among people experiencing mental illness, given the benefits to both mental and physical health outcomes. PMID- 26139699 TI - A decade of peace: Mental health issues and service developments in the Solomon Islands since 2003. AB - OBJECTIVE: To describe the impact on mental health and psychosocial wellbeing of the armed conflict that occurred in the Solomon Islands from 1998-2003 and the subsequent political unrest and natural disasters, and the developments in mental health services since 2003. METHOD: A literature and document review was conducted, supplemented by the written reflections of senior staff in the Solomon Islands Mental Health Service. RESULTS: Conflict and natural disaster have had a significant impact on the mental health and functioning of individuals, families and communities. National health system reform has been accompanied by the reorientation of the mental health services from custodial care to care in the community and greater emphasis on mental health promotion and prevention. The dedication of the small group of Solomon Islands mental health professionals, supported by local health service managers and external donors, has been a major strength. However, they face significant challenges. CONCLUSIONS: Continued investment in mental health, including the treatment and prevention of mental and substance use disorders, is essential for mental health and development outcomes. All development stakeholders, including civil society, government, academic and research institutions, and development partners, have a role to play. PMID- 26139701 TI - Anxiety and substance use disorders: a worrying combination. AB - OBJECTIVES: Individuals with co-occurring substance use and anxiety disorders can present as a diagnostic challenge. This article aims to provide clinicians with an overview of practical approaches to assessment and treatment of this common co morbidity. CONCLUSIONS: A comprehensive assessment can assist in formulating a holistic management plan that incorporates adapted psychological and pharmacological therapies to address both substance use and anxiety disorders in an integrated manner. PMID- 26139700 TI - Experience from mental health clinics held during medical service camps in Fiji. AB - OBJECTIVE: We aim to describe the experience and findings of mental health clinics held during medical service camps in the rural settings of Fiji. METHOD: Descriptive data collated at the end of the medical camps across 2011-2014 are used to highlight the main findings. RESULTS: The exposure to mental health assessments and brief interventions at these camps was a validating experience for both individuals and medical students attending the clinics. The most common presentations can be categorised under symptoms of depression, anxiety and relationship problems. CONCLUSIONS: The accessibility of mental health support services is a challenge in Fiji. Medical service camps can form an important pathway in promoting mental health awareness, especially amongst the rural communities of Fiji, and a useful platform for medical students to acquire some clinical exposure. PMID- 26139702 TI - Visualizing psychiatric formulation. AB - OBJECTIVE: Despite the importance of psychiatric formulation, it remains one of the most challenging tasks for medical students and trainees. To facilitate teaching and learning this essential skill, we propose a visual metaphor in order to conceptualise psychiatric formulation. CONCLUSIONS: It is expected that this paper will assist educators and learners to better conceptualise psychiatric formulation through activating prior knowledge through this visual metaphor. Future educational research will determine the effectiveness of this proposed learning tool. PMID- 26139703 TI - An audit of assessment and outcome of intervention at a quit smoking clinic in a homeless hostel. AB - OBJECTIVE: We aim to report on smoking history, mental and physical health, and the results of interventions provided by a Quit Smoking Clinic (QSC) at a Sydney homeless men's shelter. METHODS: We undertook an audit of questionnaires administered during the first QSC visit and a review of outcomes of QSC clients who attended the clinic more than once. RESULTS: A total of 144 men were assessed at the QSC, with mean age 45.2 years (22-71) and mean smoking duration of 29 years. About half were receiving treatment for psychotic illness, and there were high rates of other psychiatric disorders, physical illness and substance use disorder. Carbon monoxide (CO) readings were significantly higher for those smoking discarded cigarette butts. Among the subset of clients who attended the clinic more than once (n=56), only four quit for more than a month and one for a year. However, the reported number of cigarettes smoked per day was significantly lower (p=0.001), with a significant reduction in CO (p<0.008). CONCLUSIONS: This study confirms the difficulty that homeless men experience in quitting smoking, but demonstrates the potential to reduce the physical and financial harm of smoking through cessation support interventions in this setting. PMID- 26139704 TI - An audit of general practitioner involvement in public community mental health care. AB - OBJECTIVE: Existing guidelines suggest that collaboration between general practitioners and mental health services may improve the physical health of people with serious mental illness. This study investigated the extent of general practitioner involvement in a community mental health centre and examined whether the presence of a documented general practitioner in the patient's medical records was associated with markers of better health outcomes. METHODS: The medical records of current patients were audited, including those receiving medical care and case management and those only receiving medical care. The demographic and diagnostic information, evidence of metabolic screening, blood test results, and medications of patients with a recorded general practitioner were compared with those of patients with no recorded general practitioner. RESULTS: Ninety-eight of 191 (51%) of patients had details of a general practitioner documented in their medical records. There were no significant differences in rates of metabolic screening between the two groups. Those with a general practitioner had more medical diagnoses and were taking a greater number of psychiatric medications. CONCLUSION: Although the medical comorbidities of serious mental illness are becoming increasingly recognised, our findings suggest the need for ongoing and coordinated efforts by policymakers, general practitioners, mental health services and patients to ensure the health and longevity of people with serious mental illness. PMID- 26139705 TI - Marriage equality is a mental health issue. AB - OBJECTIVE: We aim to review marriage equality in New Zealand and Australia and critically evaluate the health impact of such a legal change. METHOD: We undertook a review of the literature using the search terms "marriage equality", "same sex marriage" and "gay marriage" in combination with "health", "wellbeing", "psych*", "mental illness" and "distress". This search included medical literature, legal literature and mass media. RESULTS: This review indicates that Lesbian, Gay, Bisexual, Transgender and Intersex (LGBTI) people disproportionately face negative health stressors and negative health events compared with the general population and this is related to the stress of being a stigmatised minority group. The evidence strongly supports the proposition that marriage equality is related to improved health outcomes. A diverse range of professional health groups advocate for the legislative progression to marriage equality. The authors found no evidence that marriage equality harms opposite-sex marriage. CONCLUSION: Marriage equality is still lacking in Australia and as a positive correlate of health should be strongly supported. PMID- 26139707 TI - Density functional theory study of the thermodynamic and elastic properties of Ni based superalloys. AB - The thermophysical properties of Ni-based single-crystal superalloys were investigated using first-principles calculations combined with the quasiharmonic approximation. The effect of alloying elements X (X = Re, Ru, Ta, W, Mo, Cr, and Co) on the thermophysical properties of the gamma-Ni and gamma'-Ni3Al phases was investigated. The calculations showed that alloying can effectively adjust the lattice misfit between the two phases, and Cr can suppress lattice misfit and may improve the creep resistance of alloys. At 0 K, doping with refractory elements leads to tetragonal shear softening of the gamma-Ni phase. For gamma-Ni, Re, Ru, Cr, and Co slightly increase c44, while Mo, W, and Ta decrease c44. Importantly, high-temperature relative hardening was found to occur close to the service temperature of the superalloy, at which Ru and Cr increase c' and Mo and W increase c44 of gamma-Ni. For the gamma'-Ni3Al phase, all of the alloying elements except Co considerably increase c' and c44. Re and W at the Al site were found to most effectively harden the gamma'-Ni3Al phase. The thermophysical and elastic properties were fully understood by analysis of the electronic structures and phonon spectra. It was found that the electronic density of states (DOS) can account for elastic hardening due to alloying. The phonon spectra along with electronic DOS analysis showed that alloying not only strengthens the first nearest neighbor Ni-X bond through additional d-d hybridization, but it is also important for stiffening the second nearest neighbor Al-X bonding through p-band filling. PMID- 26139708 TI - Draft Genome Sequence of Picalivirus D Recovered from San Francisco Wastewater. AB - We report here the draft genome sequence of picalivirus D, a member of picalivirus, a picorna-like superfamily, and likely member of the order Picornavirales, assembled from metagenomic sequencing of organisms in San Francisco wastewater. This virus likely constitutes a novel genus within the picalivirus family. PMID- 26139709 TI - Draft Genome Sequence of Tombunodavirus UC1. AB - We report here the draft genome sequence of tombunodavirus UC1 assembled from metagenomic sequencing of organisms in San Francisco wastewater. This virus shares hallmarks of members of the Tombusviridae and the nodavirus-like Plasmopara halstedii and Sclerophthora macrospora viruses. PMID- 26139710 TI - Draft Genome Sequence of Laverivirus UC1, a Dicistrovirus-Like RNA Virus Featuring an Unusual Genome Organization. AB - We report the draft genome sequence of Laverivirus UC1, assembled from San Francisco wastewater. This dicistronic RNA virus bears some similarity to dicistroviruses; however, it appears to have a unique genome organization relative to all other known RNA viruses. PMID- 26139711 TI - Complete Genomic Sequence of Issyk-Kul Virus. AB - Issyk-Kul virus (ISKV) is an ungrouped virus tentatively assigned to the Bunyaviridae family and is associated with an acute febrile illness in several central Asian countries. Using next-generation sequencing technologies, we report here the full-genome sequence for this novel unclassified arboviral pathogen circulating in central Asia. PMID- 26139712 TI - Draft Genome Sequence of Pseudomonas aeruginosa Strain WS136, a Highly Cytotoxic ExoS-Positive Wound Isolate Recovered from Pyoderma Gangrenosum. AB - Pseudomonas aeruginosa is an opportunistic pathogen that typically infects patients with a compromised immune defense. Here, we present the improved 6.5-Mb draft genome of strain WS136, an ExoS-positive and ExoU-negative highly cytotoxic chronic wound isolate recovered from pyoderma gangrenosum of a patient who received bone marrow transplantation. PMID- 26139713 TI - Draft Genome Sequence of a Multidrug-Resistant Acinetobacter baumannii Strain from Chile. AB - Acinetobacter baumannii strain Ab5 was isolated in the year 2007 in Chile, being one of the first multidrug-resistant (MDR) cases reported in the country. Here, we present the very first draft genome sequence of an MDR Chilean strain, which shows the presence of diverse resistance and acquired virulence genes. PMID- 26139714 TI - Complete Genome Sequence of Salmonella enterica subsp. enterica Serovar Agona 460004 2-1, Associated with a Multistate Outbreak in the United States. AB - Within the last several years, Salmonella enterica subsp. enterica serovar Agona has been among the 20 most frequently isolated serovars in clinical cases of salmonellosis. In this report, the complete genome sequence of S. Agona strain 460004 2-1 isolated from unsweetened puffed-rice cereal during a multistate outbreak in 2008 was sequenced using single-molecule real-time DNA sequencing. PMID- 26139715 TI - Complete Genome Sequence of Bacilli bacterium Strain VT-13-104 Isolated from the Intestine of a Patient with Duodenal Cancer. AB - We report the complete genome sequence of Bacilli bacterium strain VT-13-104 isolated from the intestine of a patient with duodenal cancer. The genome is composed of 3,573,421 bp, with a G+C content of 35.7%. It possesses 3,254 predicted protein-coding genes encoding multidrug resistance transporters, resistance to antibiotics, and virulence factors. PMID- 26139716 TI - Draft Genome Sequences of Bifidobacterium angulatum GT102 and Bifidobacterium adolescentis 150: Focusing on the Genes Potentially Involved in the Gut-Brain Axis. AB - The draft genome sequences of Bifidobacterium angulatum GT102 and Bifidobacterium adolescentis 150 strains isolated from the human intestinal microbiota are reported. Both strains are able to produce gamma-aminobutyric acid (GABA). Detailed genomes analysis will help to understand the role of GABA in the functioning of gut-brain axis. PMID- 26139717 TI - Complete Genome Sequence of Bacillus thuringiensis Serovar Tolworthi Strain Pasteur Institute Standard. AB - The genome sequence of Bacillus thuringiensis serovar tolworthi strain Pasteur Institute Standard was determined. The genome consists of a 5.9-Mb chromosome and eight plasmids, one of which is linear. The second largest plasmid (293 kb) carries the genes encoding insecticidal proteins. PMID- 26139718 TI - Complete Genome Sequence of Rhodococcus sp. Strain IcdP1 Shows Diverse Catabolic Potential. AB - The complete genome sequence of Rhodococcus sp. strain IcdP1 is presented here. This organism was shown to degrade a broad range of high-molecular-weight polycyclic aromatic hydrocarbons and organochlorine pesticides. The sequence data can be used to predict genes for xenobiotic biodegradation and metabolism. PMID- 26139719 TI - Complete Genome Sequence of Mycoplasma gallinaceum. AB - Mycoplasma gallinaceum strain B2096 8B was isolated from domestic chickens in South Africa. The 845,307-bp full genome was sequenced, assembled, and annotated. PMID- 26139720 TI - Whole-Genome Sequence of Multidrug-Resistant Staphylococcus caprae Strain 9557, Isolated from Cerebrospinal Fluid. AB - Staphylococcus caprae strain 9557 was isolated from a cerebrospinal fluid sample. The assembled genome contained 2,747,651-bp nucleotides with 33.34% GC content. Consistent with its phenotypic characteristics, the genome harbors a varying repertoire of putative virulence factors involved in invasion, survival, and growth in the host cells. PMID- 26139721 TI - Draft Genome Sequence of Jiangella alkaliphila KCTC 19222T, Isolated from Cave Soil in Jeju, Republic of Korea. AB - We report the draft genome sequence of Jiangella alkaliphila KCTC 19222(T), isolated from cave soil in Jeju, Republic of Korea. This genome sequence, together with the previously sequenced J. gansuensis strain DSM 44835(T), identified from a desert environmental source, will give us a better understanding of the school of "evolutionary taxonomy." PMID- 26139722 TI - Complete Genome Sequences of emm6 Streptococcus pyogenes JRS4 and Parental Strain D471. AB - We report the complete genome assemblies of the group A Streptococcus pyogenes serotype emm6 strain D471 and its streptomycin-resistant derivative JRS4. Both of these well-studied laboratory strains have been extensively characterized over the past three decades and have been instrumental in the discovery of multiple aspects of streptococcal pathogenesis. PMID- 26139723 TI - Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Give, Isolated from an Imported Chili Powder Product. AB - We report the genome sequence of Salmonella enterica subsp. enterica serovar Give (CFSAN012622), isolated from imported chili powder in 2014. This genome contains genes previously reported to be specific only to S. enterica serovar Enteritidis. This strain shows a unique pulsed-field gel electrophoresis (PFGE) pattern clustering with serovar Enteritidis (JEG X01.0005). PMID- 26139724 TI - Draft Genome Sequences of Vibrio alginolyticus Strains V1 and V2, Opportunistic Marine Pathogens. AB - We announce the draft genome sequences of Vibrio alginolyticus strains V1 and V2, isolated from juvenile Sparus aurata and Dentex dentex, respectively, during outbreaks of vibriosis. The genome sequences are 5,257,950 bp with a G+C content of 44.5% for V. alginolyticus V1 and 5,068,299 bp with a G+C content of 44.8% for strain V2. These genomes provide further insights into the putative virulence factors, prophage carriage, and evolution of this opportunistic marine pathogen. PMID- 26139725 TI - Draft Genome Sequence of Vibrio parahaemolyticus VH3, Isolated from an Aquaculture Environment in Greece. AB - Vibrio parahaemolyticus is an important foodborne pathogen responsible for gastroenteritis outbreaks globally. It has also been identified as an important pathogen in aquatic organisms. Here, we report a draft genome sequence of V. parahaemolyticus, strain VH3, isolated from farmed juvenile greater amberjack, Seriola dumerili, in Greece. PMID- 26139726 TI - Draft Genome Sequences of Two Pyrazinamide-Resistant Clinical Isolates, Mycobacterium tuberculosis 13-4152 and 13-2459. AB - We report draft genome sequences of two pyrazinamide (PZA)-resistant isolates, Mycobacterium tuberculosis 13-4152 and 13-2459. Isolate 13-4152 is PZA resistant, though it lacks mutations in known genes of PZA resistance. The comparative analysis of these genomes with those stored in GenBank revealed unique mutations, which may elucidate new mechanisms of PZA resistance. PMID- 26139727 TI - Complete and Assembled Genome Sequence of Staphylococcus aureus RKI4, a Food Poisoning Strain Exhibiting a Novel S. aureus Pathogenicity Island Carrying seb. AB - The genome of Staphylococcus aureus RKI4, a strain isolated from feces of a patient in a case of staphylococcal food poisoning, was sequenced using combined Illumina and single-molecule real-time sequencing. Hierarchical assembly of the genome resulted in a 2,725,654-bp chromosome and a 17,905-bp mobile genetic element. PMID- 26139728 TI - Nuances of social media in medical journalism. PMID- 26139729 TI - Hybrid atrial fibrillation ablations and the increasing importance of the hybrid cardiovascular laboratory operating room. PMID- 26139730 TI - Converting data into information and knowledge: The promise and the reality of electronic medical records. PMID- 26139731 TI - Do preoperative pulmonary function indices predict morbidity after coronary artery bypass surgery? AB - CONTEXT: The reported prevalence of chronic obstructive pulmonary disease (COPD) varies among different groups of cardiac surgical patients. Moreover, the prognostic value of preoperative COPD in outcome prediction is controversial. AIMS: The present study assessed the morbidity in the different levels of COPD severity and the role of pulmonary function indices in predicting morbidity in patients undergoing coronary artery bypass graft (CABG). SETTINGS AND DESIGN: Patients who were candidates for isolated CABG with cardiopulmonary bypass who were recruited for Tehran Heart Center-Coronary Outcome Measurement Study. METHODS: Based on spirometry findings, diagnosis of COPD was considered based on Global Initiative for Chronic Obstructive Lung Disease category as forced expiratory volume in 1 s [FEV1]/forced vital capacity <0.7 (absolute value, not the percentage of the predicted). Society of Thoracic Surgeons (STS) definition was used for determining COPD severity and the patients were divided into three groups: Control group (FEV1 >75% predicted), mild (FEV1 60-75% predicted), moderate (FEV1 50-59% predicted), severe (FEV1<50% predicted). The preoperative pulmonary function indices were assessed as predictors, and postoperative morbidity was considered the surgical outcome. RESULTS: This study included 566 consecutive patients. Patients with and without COPD were similar regarding baseline characteristics and clinical data. Hypertension, recent myocardial infarction, and low ejection fraction were higher in patients with different degrees of COPD than the control group while male gender was more frequent in control patients than the others. Restrictive lung disease and current cigarette smoking did not have any significant impact on postoperative complications. We found a borderline P = 0.057 with respect to respiratory failure among different patients of COPD severity so that 14.1% patients in control group, 23.5% in mild, 23.4% in moderate, and 21.9% in severe COPD categories developed respiratory failure after CABG surgery. CONCLUSION: Among post-CABG complications, patients with different levels of COPD based on STS definition, more frequently developed respiratory failure. This finding may imply the prognostic value of preoperative pulmonary function test for determining COPD severity and postoperative morbidities. PMID- 26139732 TI - Effect of lateral body position on transesophageal echocardiography images and the association with patient characteristics: A prospective observational study. AB - BACKGROUND: Changes in heart position are occasionally observed on the transesophageal echocardiography (TEE) image screen after changing the body position from supine to lateral, although the magnitude of change in cardiac position varies individually. We hypothesized that this variation is associated with certain patient characteristics and evaluated how lateral positioning affects visualization of the heart on TEE and whether the magnitude of change in the heart position correlates with patient characteristics. METHODS: Fifty-three lung resection patients were enrolled. Two angle and two length parameters (DqTV , DqAP , DL TV , and DL AP ) were defined to describe location change of the lateral tricuspid annulus and right ventricular apex on the TEE image between supine and lateral position. The correlation coefficients were calculated between these four parameters and patient characteristics, including age, body mass index (BMI), epicardial fat thickness, and pulmonary function variables. RESULTS: The DqTV correlated positively and inversely with BMI in both right and left lateral patients (right: r = 0.6365, P = 0.0034; left: r = -0.6616, P < 0.0001, respectively). In left lateral patients, the DqTV correlated inversely with epicardial fat thickness (r = -0.4879, P = 0.0182), and the DL AP correlated positively with the forced vital capacity percent predicted (r = 0.5736, P = 0.0082). CONCLUSIONS: Lateral body positioning affects cardiac visualization on TEE, and the BMI, epicardial fat thickness, and pulmonary function moderate this effect. PMID- 26139733 TI - Cardioversion: What to choose? Etomidate or propofol. AB - CONTEXT: Electrical cardioversion is a short painful procedure to regain normal sinus rhythm requiring anaesthesia for haemodynamic stability, sedation, analgesia and early recovery. AIMS: To compare propofol and etomidate as sedatives during cardioversion. SETTINGS AND DESIGN: Single centred, prospective and randomized single blind study comprising 60 patients. SUBJECTS AND METHODS: Patients more than 18 years, American Society of Anesthesiologists I/II/III grades undergoing elective cardioversion, randomly divided to receive propofol 1 mg/kg intravenous (IV) bolus followed by 0.5 mg/kg (Group P, n = 30) or etomidate (Group E, n = 30) 0.1 mg/kg followed by 0.05 mg/kg. All patients received IV fentanyl (1 MUg/kg) before procedure. Heart rate, blood pressure (BP) (systolic BP [SBP], diastolic BP [DBP], mean arterial pressure), respiratory rate, Aldrete recovery score (ARS) and Ramsay sedation score (RSS) were assessed at 1, 2, 5, 10, 15, 20 and 30 min post cardioversion. Incidence of hypotension, respiratory depression and side effects were compared. STATISTICAL ANALYSIS USED: Student's unpaired t-test, Chi-square test and Mann-Whitney test. P < 0.05 was taken as significant. RESULTS: Group P showed significant fall in SBP, DBP, and mean BP at 2 min after cardioversion. Hypotension (33.3% Group P vs. 16.65% Group E) occurred more with propofol (P < 0.05). Group E showed better ARS at 1, 2, 5, 10, 15 and 20 min. Time required to attain RSS = 2 (659.1 s Group P and 435.7 s Group E) indicated longer recovery with propofol. Left atrial size (35.5-42.5 mm) did not affect success rate of cardioversion (80% Group P vs. 83.3% Group E). Incidence of myoclonus (Group E 26.67% vs. Group P 0%) showed significant difference. CONCLUSIONS: Etomidate/fentanyl is superior over propofol/fentanyl during cardioversion for quick recovery and haemodynamic stability. PMID- 26139734 TI - Noninvasive estimation of left atrial pressure with transesophageal echocardiography. AB - BACKGROUND: The pulmonary artery catheter (PAC) has historically been used to measure cardiac filling pressures of which pulmonary capillary wedge pressure (PCWP) has been used as a surrogate of left atrial pressure (LAP) and left ventricular end-diastolic pressure. Increasingly, the use of the PAC has been questioned in the perioperative period with multiple large studies unable to clearly demonstrate benefit in any group of patients, resulting in a declining use in the perioperative period. Alternative methods for the noninvasive estimation of left-sided filling pressures are required. Echocardiography has been used to provide noninvasive estimation of PCWP and LAP, based on evaluating mitral inflow velocity with the E and A waves and looking at movement of the mitral annulus with tissue Doppler (e'). AIM: The aim of our study was to assess the relationship between PCWP and E/e' in cardiac surgical patients with transesophageal echocardiography (TOE). DESIGN: A prospective observational study. SETTING: Cardiac surgical patients in a single quaternary referral university teaching hospital. METHODS: The ratio of mitral inflow velocity (E wave) to mitral annular tissue velocity (e') (the E/e' ratio) and PCWP of 91 patients undergoing general anesthesia and cardiac surgery were simultaneously recorded, with the use of TOE and a PAC. RESULTS: The correlation between E/e' and PCWP was modest with a Spearman rank correlation coefficient of 0.29 (P = 0.005). The area under the receiver operating characteristic curve for using E/e' to predict elevated PCWP (>=18 mmHg) was 0.6825 (95% confidence interval: 0.57 0.80), indicating some predictive utility. The optimum threshold value of E/e' was 10 which had 71% sensitivity and 60% specificity to predict a PCWP >=18 mmHg. CONCLUSIONS: Noninvasive measurements of E/e' in general cardiac surgical patients have only a modest correlation and does not reliably estimate PCWP. PMID- 26139735 TI - Assessment of feasibility and efficacy of Class IV laser therapy for postoperative pain relief in off-pump coronary artery bypass surgery patients: A pilot study. AB - BACKGROUND: Laser therapy, for its established analgesic properties with minimal side effects, has been used for the treatment of chronic pain. However, it has not been used for the treatment of acute postoperative pain. This pilot study was designed to assess the feasibility and efficacy of Class IV laser on postoperative pain relief following off-pump coronary artery bypass graft (OPCABG) surgery, as a component of multimodal analgesia (MMA) technique. METHODS: This open observational prospective study comprised of 100 adult patients (84 male, 16 female) who underwent OPCABG through sternotomy. For postoperative analgesia, they were subjected to laser therapy subjected to laser therapy in addition to the standard institutional pain management protocol comprising of IV infusion/bolus of tramadol and paracetamol and fentanyl bolus as rescue analgesic. Pain intensity was measured by Verbal Rating Scale (VRS). The laser therapy was scheduled as once a day regime for three consecutive postoperative days (PODs) starting on POD 1, 30 min following tracheal extubation. The subsequent laser applications were also scheduled at the same time of the day as on day 1 if VRS was >=5. 10 W Class IV laser was applied over 150 cm2 sternal wound area for 150 s. VRS was used to assess pain severity and was recorded for statistical analysis using Friedman Test. RESULTS: The mean (standard deviation [SD]) VRS of all the 100 patients just before application of the first dose of laser was 7.31 (0.94) while on MMT; the same fell to 4.0 (1.279) and 3.40 (2.697) at 1 h and 24 h respectively following first dose of laser. The change of VRS over first 24 h among all the 100 patients was statistically significant (P = 0.000). Laser was re-applied in 40 patients whose VRS was >=5 (mean [SD] - 6.38 [0.868]) at 24th h. After receiving the 2nd dose of laser the VRS scores fell significantly (P = 0.000) and became 0 at 54th h. No patients required 3rd dose of the laser. No patient required rescue analgesic while on laser therapy. CONCLUSION: Class IV laser can be an effective technique for postoperative analgesia following OPCABG surgery through sternotomy when included as a component of MMA technique. PMID- 26139736 TI - Effect of dexmeditomidine on postoperative junctional ectopic tachycardia after complete surgical repair of tetralogy of Fallot: A prospective randomized controlled study. AB - INTRODUCTION: Incidence of junctional ectopic tachycardia (JET) after repair of tetralogy of Fallot (TOF) is 5.6-14%. Dexmeditomidine is a a-2 adrenoceptor agonist modulates the release of catecholamine, resulting in bradycardia and hypotension. These effects are being explored as a therapeutic option for the prevention of perioperative tachyarrhythmia. We undertook this study to examine possible preventive effects of dexmedetomidine on postoperative JET and its impact on the duration of ventilation time and length of Intensive Care Unit stay. METHODS: After obtaining approval from the hospitals ethics committee and written informed consent from parents, this quasi-randomized trial was initiated. Of 94 patients, 47 patients received dexmedetomidine (dexmedetomidine group) and 47 patients did not receive the drug (control group). RESULTS: Dexmedetomidine group had more number of complex variants like TOF with an absent pulmonary valve or pulmonary atresia (P = 0.041). Hematocrit on cardiopulmonary bypass (CPB), heart rate while coming off from CPB and inotrope score was significantly low in the dexmedetomidine group compared to control group. The incidence of JET was significantly low in dexmedetomidine group (P = 0.040) compared to control group. CONCLUSIONS: Dexmedetomidine may have a potential benefit of preventing perioperative JET. PMID- 26139737 TI - Percutaneous tracheostomy in patients on anticoagulants. AB - AIMS: To determine if percutaneous tracheostomy is safe in critically ill patients treated with anticoagulant therapies. SETTINGS AND DESIGN: Single-center retrospective study including all the patients who underwent percutaneous dilatational tracheostomy (PDT) placement over a 1-year period in a 14-bed, cardiothoracic and vascular Intensive Care Unit (ICU). MATERIALS AND METHODS: Patients demographics and characteristics, anticoagulant and antiplatelet therapies, coagulation profile, performed technique and use of bronchoscopic guidance were retrieved. RESULTS: Thirty-six patients (2.7% of the overall ICU population) underwent PDT over the study period. Twenty-six (72%) patients were on anticoagulation therapy, 1 patient was on antiplatelet therapy and 2 further patients received prophylactic doses of low molecular weight heparin. Only 4 patients had normal coagulation profile and were not receiving anticoagulant or antiplatelet therapies. Overall, bleeding of any severity complicated 19% of PDT. No procedure-related deaths occurred. CONCLUSIONS: PDT was proved to be safe even in critically ill-patients treated with anticoagulant therapies. Larger prospective studies are needed to confirm our findings. PMID- 26139738 TI - Validation of the European System for Cardiac Operative Risk Evaluation-II model in an urban Indian population and comparison with three other risk scoring systems. AB - AIMS AND OBJECTIVES: The aims were to compare the European System for Cardiac Operative Risk Evaluation (EuroSCORE)-II system against three established risk scoring systems for predictive accuracy in an urban Indian population and suggest improvements or amendments in the existing scoring system for adaptation in Indian population. MATERIALS AND METHODS: EuroSCORE-II, Parsonnet score, System 97 score, and Cleveland score were obtained preoperatively for 1098 consecutive patients. EuroSCORE-II system was analyzed in comparison to each of the above three scoring systems in an urban Indian population. Calibrations of scoring systems were assessed using Hosmer-Lemeshow test. Areas under receiver operating characteristics (ROC) curves were compared according to the statistical approach suggested by Hanley and McNeil. RESULTS: All EuroSCORE-II subgroups had highly significant P values stating good predictive mortality, except high-risk group (P = 0.175). The analysis of ROC curves of different scoring systems showed that the highest predictive value for mortality was calculated for the System-97 score followed by the Cleveland score. System-97 revealed extremely high predictive accuracies across all subgroups (curve area >80%). This difference in predictive accuracy was found to be statistically significant (P < 0.001). CONCLUSIONS: The present study suggests that the EuroSCORE-II model in its present form is not validated for use in the Indian population. An interesting observation was significantly accurate predictive abilities of the System-97 score. PMID- 26139739 TI - Mid-term survival after transcatheter aortic valve implantation: Results with respect to the anesthetic management and to the access route (transfemoral versus transapical). AB - CONTEXT: Several studies have analyzed the long-term survival after transcatheter aortic valve implantation (TAVI). However, no previous studies have looked at survival beyond 1-year with respect to the type of anesthesia. AIMS: The aim was to evaluate the mid-term survival after TAVI with respect to the type of anesthesia (general anesthesia [GA] vs. local anesthesia +/- sedation [LASedation]) or the type of procedure (transfemoral [transfem] vs. transapical TAVI) performed. SETTINGS AND DESIGN: Retrospective cohort study. SUBJECTS AND METHODS: This retrospective study included TAVI's between January 2009 and June 2013. Patients were divided into three groups: transfem TAVI under GA, transfem TAVI under LASedation and transapical TAVI. A total of 176 patients were eligible. The following clinical outcomes were evaluated: (1) Mortality, (2) Major cardiovascular complications, (3) Conduction abnormalities and arrhythmias, (4) Acute kidney injury, (5) Aortic regurgitation, (6) Neurologic events, (7) Vascular complications, (8) Pulmonary complications, (9) Bleeding, (10) Infectious complications, (11) Delirium. STATISTICAL ANALYSIS USED: A Kruskal Wallis test was performed to test significance between the three groups for quantitative variables. Categorical variables were compared using a Chi-square test. Survival was estimated using Kaplan-Meier method. RESULTS: There was no statistically significant difference between the survival of both transfem TAVI's (P = 0.46). The short-term outcome of the transfem TAVI groups was better than the transapical arm, but their mid-term survival did not show any significant difference (P = 0.69 transapical vs. transfem GA; P = 0.07 transapical vs. transfem LASedation). CONCLUSIONS: Our results demonstrate that the type of anesthesia and the access route do not influence mid-term survival after TAVI. PMID- 26139740 TI - Comparison of tapentadol with tramadol for analgesia after cardiac surgery. AB - BACKGROUND: Tapentadol is a relatively new analgesic. We decided to compare it with tramadol for their various effects after cardiac surgery. SETTING: A study in a tertiary care hospital. MATERIALS AND METHODS: Sixty adults undergoing cardiac surgery were divided into 2 groups of 30 each by computerized random allotment (Group X = tapentadol 50 mg oral and Group Y = tramadol 100 mg oral). Informed Consent and Institutional Ethics Committee approval were obtained. The patients were given either drug X or drug Y after extubation in this single blinded study, wherein the data collectors and analyzers were blinded to the study. All patients received oral paracetamol qds and either drug X or drug Y tds. The pain score was noted on a Visual Analog Scale before each drug dose, 3 h later and on coughing. Heart rate, respiratory rate, and blood pressure were recorded before the drug dose and 3 h later. Postoperative nausea or vomiting (PONV), temperature, and modified Glasgow Coma Scale readings were recorded. The above readings were obtained for 6 doses (up to 48 h after extubation). STATISTICS: t-test, Pearson Chi-square test, Fisher exact test, and Mantel Haenszel test were used for statistics. RESULTS: Tapentadol group patients had significantly better analgesia 3 h after the drug and "on coughing" than tramadol group. The difference in their effects on blood creatinine levels, temperature, hemodynamics, oxygen saturation, and respiratory rate were not clinically significant. Tapentadol produced lesser drowsiness and lesser vomiting than tramadol. CONCLUSIONS: Tapentadol, due to its norepinephrine reuptake inhibition properties, in addition to mu agonist, is a better analgesic than tramadol and has lesser PONV. PMID- 26139741 TI - Heart valve surgery in patients with homozygous sickle cell disease: A management strategy. AB - BACKGROUND: Patients with the homozygous sickle cell disease have increased perioperative mortality. Some indications like heart valve surgery, may justify an exchange blood transfusion to reduce the proportion of hemoglobin S (HbS) and complications. SUBJECTS AND METHODS: We report two female cases aged 20 and 27, of African origin with homozygous sickle cell anemia who underwent heart valve surgery to treat mitral valve regurgitation. This presentation describes the perioperative considerations including anesthesia and postoperative care. RESULTS: A partial exchange blood transfusion decreased HbS levels from respectively, 90% and 84%, 9% to 27% and 34%, and simultaneously treated the anemia. Neither sickling crisis nor acidosis occurred in any patient, and no special postoperative complication occurred. Average hospital stay was 10 days. Currently, the two patients remain alive and free of cardiac symptoms. DISCUSSION: Although the presence of sickle cell disorders is associated with increased risk of sickling and thus vaso-occlusive complications, they should not be taken as a contraindication for heart valve surgery. Nevertheless, monitoring of certain parameters such as venous, arterial oxygen content, pH, and body temperature is mandatory for a better outcome. Furthermore, preoperative exchange transfusion has a positive influence on the outcome of surgery and on the survival of patients undergoing heart valves surgery. Avoiding intraoperative hypoxia, hypothermia, and vaso-constrictive agents, minimizing HbS levels with preoperative exchange transfusion, and ensuring a stress-free environment with the judicious use of sedatives made surgery relatively safe in these cases. PMID- 26139742 TI - Weight-for-age standard score - distribution and effect on in-hospital mortality: A retrospective analysis in pediatric cardiac surgery. AB - OBJECTIVE: To study the distribution of weight for age standard score (Z score) in pediatric cardiac surgery and its effect on in-hospital mortality. INTRODUCTION: WHO recommends Standard Score (Z score) to quantify and describe anthropometric data. The distribution of weight for age Z score and its effect on mortality in congenital heart surgery has not been studied. METHODS: All patients of younger than 5 years who underwent cardiac surgery from July 2007 to June 2013, under single surgical unit at our institute were enrolled. Z score for weight for age was calculated. Patients were classified according to Z score and mortality across the classes was compared. Discrimination and calibration of the for Z score model was assessed. Improvement in predictability of mortality after addition of Z score to Aristotle Comprehensive Complexity (ACC) score was analyzed. RESULTS: The median Z score was -3.2 (Interquartile range -4.24 to 1.91] with weight (mean+/-SD) of 8.4 +/- 3.38 kg. Overall mortality was 11.5%. 71% and 52.59% of patients had Z score < -2 and < -3 respectively. Lower Z score classes were associated with progressively increasing mortality. Z score as continuous variable was associated with O.R. of 0.622 (95% CI- 0.527 to 0.733, P < 0.0001) for in-hospital mortality and remained significant predictor even after adjusting for age, gender, bypass duration and ACC score. Addition of Z score to ACC score improved its predictability for in-hosptial mortality (deltaC - 0.0661 [95% CI - 0.017 to 0.0595, P = 0.0169], IDI- 3.83% [95% CI - 0.017 to 0.0595, P = 0.00042]). CONCLUSION: Z scores were lower in our cohort and were associated with in-hospital mortality. Addition of Z score to ACC score significantly improves predictive ability for in-hospital mortality. PMID- 26139743 TI - Propensity-matched analysis of association between preoperative anemia and in hospital mortality in cardiac surgical patients undergoing valvular heart surgeries. AB - INTRODUCTION: Anaemia is associated with increased post-operative morbidity and mortality. We retrospectively assess the relationship between preoperative anaemia and in-hospital mortality in valvular cardiac surgical population. MATERIALS AND METHODS: Data from consecutive adult patients who underwent valvular repair/ replacement at our institute from January 2010 to April 2014 were collected from hospital records. Anaemia was defined according to WHO criteria (hemoglobin <13g/dl for males and <12g/dl for females). 1:1 matching was done for anemic and non-anemic patients based on propensity for potentially confounding variables. Logistic regression was used to evaluate the relationship between anaemia and in-hospital mortality. MatchIt package for R software was used for propensity matching and SPSS 16.0.0 was used for statistical analysis. RESULTS: 2449 patients undergoing valvular surgery with or without coronary artery grafting were included. Anaemia was present in 37.1% (33.91% among males & 40.88% among females). Unadjusted OR for mortality was 1.6 in anemic group (95% Confidence Interval [95% CI] - 1.041-2.570; p=0.033). 1:1 matching was done on the basis of propensity score for anaemia (866 pairs). Balancing was confirmed using standardized differences. Anaemia had an OR of 1.8 for mortality (95% CI- 1.042 to 3.094, P=0.035). Hematocrit of < 20 on bypass was associated with higher mortality. CONCLUSION: Preoperative anaemia is an independent risk factor associated with in-hospital mortality in patients undergoing valvular heart surgery. PMID- 26139744 TI - Transesophageal echocardiography estimation of coronary sinus blood flow for the adequacy of revascularization in patients undergoing off-pump coronary artery bypass graft. AB - AIMS AND OBJECTIVES: Physiologically coronary sinus (CS) drains the left coronary artery (LCA) territory. Stenosis of the branches of LCA may decrease the coronary sinus blood flow (CSBF). Any intervention that aims at restoring the flow of the stenosed vessel increases coronary artery flow that should consequently increase the CSBF. Hence, this study was undertaken to assess the CSBF before and after each branch of LCA to determine the adequacy of surgical revascularization in patients undergoing elective off pump coronary artery bypass grafting (OPCAB) using transesophageal echocardiography (TEE). MATERIALS AND METHODS: Thirty consecutive patients scheduled for elective OPCAB were enrolled. CSBF was assessed before and after each branch of LCA revascularization using TEE. Left internal mammary artery (LIMA) Doppler was also obtained post LIMA to left anterior descending (LAD) grafting. RESULTS: Hemodynamic and echocardiographic variables were compared by means of Student's t-test for paired data before and after revascularization. The CSBF per beat (1.28 +/- 0.71), CSBF per minute (92.59 +/- 59.32) and total velocity time integral (VTI) (8.93 +/- 4.29) before LAD grafting showed statistically significant increase to CSBF per beat (1.70 +/- 0.89), CSBF per minute (130.72 +/- 74.22) and total VTI (11.96 +/- 5.68) after LAD revascularization. The CSBF per beat (1.67 +/- 1.03), CSBF per minute (131.91 +/- 86.59) and total VTI (11.00 +/- 5.53) before obtuse marginal (OM) grafting showed statistically significant increase to CSBF per beat (1.91 +/- 1.03), CSBF per min (155.20 +/- 88.70) and total VTI (12.09 +/- 5.43) after OM revascularization. In 9 patients, color flow Doppler of LIMA could be demonstrated which showed diastolic predominant blood flow after LIMA to LAD grafting. CONCLUSION: Demonstration of CSBF was simple and monitoring the trend of CSBF values before and after each graft of LCA territory will guide to determine the adequacy of surgical revascularization. PMID- 26139746 TI - Video Commentary 1: Tee for endoventricular patch plasty/dor procedure. PMID- 26139745 TI - Nonanalgesic benefits of combined thoracic epidural analgesia with general anesthesia in high risk elderly off pump coronary artery bypass patients. AB - OBJECTIVE: Epidural anesthesia is a central neuraxial block technique with many applications. It is a versatile anesthetic technique, with applications in surgery, obstetrics and pain control. Its versatility means it can be used as an anesthetic, as an analgesic adjuvant to general anesthesia, and for postoperative analgesia. Off pump coronary artery bypass (OPCAB) surgery triggers a systemic stress response as seen in coronary artery bypass grafting (CABG). Thoracic epidural anesthesia (TEA), combined with general anesthesia (GA) attenuates the stress response to CABG. There is Reduction in levels of Plasma epinephrine, Cortisol and catecholamine surge, tumor necrosis factor-Alpha( TNF alpha), interleukin-6 and leucocyte count. DESIGN: A prospective randomised non blind study. SETTING: A clinical study in a multi specialty hospital. PARTICIPANTS: Eighty six patients. Material and Methods/intervention: The study was approved by hospital research ethics committee and written informed consent was obtained from all patients. Patients were randomised to receive either GA plus epidural (study group) or GA only (control group). Inclusion Criteria (for participants) were Age >= 70 years, Patient posted for OPCAB surgery, and patient with comorbidities (diabetes mellitus, chronic obstructive pulmonary disease, cerebrovascular disease, peripheral vascular disease, renal dysfunction). Serum concentration of Interlukin: - 6, TNF alpha, cortisol, Troponin - I, CK-MB, and HsCRP (highly sensitive C reactive protein), was compared for both the group and venous blood samples were collected and compared just after induction, at day 2, and day 5 postoperatively. Time to mobilization, extubation, total intensive care unit stay and hospital stay were noted and compared. Independent t test was used for statistical analysis. PRIMARY OUTCOMES: Postoperative complications, total intensive care unit stay and hospital stay. Secondary Outcome: Stress response. RESULT: Study group showed decreased Interlukin - 6 at day 2, TNF alpha at day 2 and 5,troponin I at day 5, and decreased total hospital stay ( p < 0.05). CONCLUSION: Thoracic epidural anesthesia decreases stress and inflammatory response to surgery and decreases hospital stay. However a large multicentre study may be needed to confirm it. PMID- 26139747 TI - Video Commentary 2: "Tee for direct closure for LV aneurysm repair". PMID- 26139748 TI - Inhaled therapy for the management of perioperative pulmonary hypertension. AB - Patients with pulmonary hypertension (PH) are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP). Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary-specific vasodilator, nitric oxide (NO), has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil), NO-donating drugs (sodium nitroprusside, nitroglycerin, and nitrite), and phosphodiesterase inhibitors (milrinone, sildenafil) may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators. PMID- 26139750 TI - Malpositioning of right internal jugular central venous catheter into right external jugular vein forming "figure of eight". PMID- 26139749 TI - Brugada syndrome and its relevance in the perioperative period. AB - Brugada syndrome is an autosomal dominant genetic disorder associated with an increased risk of sudden cardiac death, as well as ventricular tachyarrhythmias.The defective cardiac sodium channels result in usual electrocardiographic findings of a coved-type ST elevation in precordial leads V1 to V3. The majority of patients have uncomplicated courses with anesthesia, surgery, and invasive procedures. However there is risk of worsening ST elevation and ventricular arrhythmias due to perioperative medications, surgical insult, electrolyte abnormalities, fever, autonomic nervous system tone, as well as other perturbations. Given the increasing numbers of patients with inherited conduction disorders presenting for non-cardiac surgery that are at risk of sudden cardiac death, safe anesthetic management depends upon a detailed knowledge of these conditions. PMID- 26139751 TI - In response to Evolutionary change: The new face of Annals of Cardiac Anesthesia. PMID- 26139752 TI - Hematuria in a child eight hours, postcardiac surgery. PMID- 26139753 TI - Left subclavian artery occlusion: Incidental transesophageal echocardiography diagnosis. PMID- 26139754 TI - Interventricular septal hydatid cyst: Transesophageal echocardiography as a therapeutic tool during bypass. AB - Cystic echinococcosis (hydatid disease) arising from infestation with a larval or adult form of the Echinococcus granulosus tapeworm is endemic in certain states of India, but affecting interventricular septum (IVS) solitarily is a scarce phenomenon. We present a rare case of transesophageal echocardiography guided management of IVS hydatid cyst even during cardiopulmonary bypass, which presented with a rather unusual complaint of repeated syncope. PMID- 26139755 TI - Obstructive membrane in arch of aorta in a case of Shone's complex. AB - Shone's complex is a rare congenital heart disease consisting of multisite obstruction on the left side of the heart. The obstructive membrane in the arch of aorta is never described among these obstructions. We report echocardiographic findings in a patient with Shone's complex with the obstructive membrane in the arch of aorta. PMID- 26139756 TI - Aneurysm: Sinus of valsalva or ventricular septal? PMID- 26139757 TI - Imaging coronary sinus in modified bicaval view. PMID- 26139758 TI - Perioperative management of a patient with Dandy Walker malformation with tetralogy of Fallot undergoing total correction and fresh homologous pericardial pulmonary valve conduit implantation: Report of a rare case. AB - Perioperative management of a patient with Dandy-Walker malformation (DWM) with tetralogy of Fallot (TOF), patent ductus arteriosus, and pulmonary artery stenosis is a great challenge to the anesthesiologist. Anesthetic management in such patients can trigger tet spells that might rapidly increase intracranial pressure (ICP), conning and even death. The increase in ICP can precipitate tet spells and further brain hypoxia. To avoid an increase in ICP during TOF corrective surgery ventriculo-peritoneal (VP) shunt should be performed before cardiac surgery. We present the first case report of a 11-month-old male baby afflicted with DWM and TOF who underwent successful TOF total corrective surgery and fresh autologous pericardial pulmonary valve conduit implantation under cardiopulmonary bypass after 1 week of VP shunt insertion. PMID- 26139759 TI - Use of dexmedetomidine as an adjunct in the treatment of paradoxical hypertension after surgical repair of coarctation of the aorta in infants. AB - Severe persistent hypertension is seen infrequently in newborns and infants, but we came across two infants who developed severe paradoxical hypertension after successful coarctation repair. Treatment of systemic hypertension following repair of coarctation of the aorta is always challenging particularly in infants. Dexmedetomidine was used successfully as an adjunct to the established anti hypertensive drugs in the immediate postoperative period in our cases to treat postoperative paradoxical hypertension. PMID- 26139760 TI - Pulmonary edema following transcatheter closure of atrial septal defect. AB - We describe an incident of development of acute pulmonary edema after the device closure of a secundum atrial septal defect in a 52-year-old lady, which was treated with inotropes, diuretics and artificial ventilation. Possibility of acute left ventricular dysfunction should be considered after the defect closure in the middle-aged patients as the left ventricular compliance may be reduced due to increased elastic stiffness and diastolic dysfunction. Baseline left atrial pressure may be > 10 mmHg in these patients. Associated risk factors for the left ventricular dysfunction are a large Qp:Qs ratio, systemic hypertension, severe pulmonary hypertension and paroxysmal atrial fibrillation. PMID- 26139761 TI - Right ventricular hydatid cyst ruptured to pericardium. AB - Cardiac hydatidosis is rare presentation of body hydatidosis. Incidence of cardiac involvements range from 5% to 5% of patients with hydatid disease. Most common site of hydatid cyst in heart is interventricular septum and left ventricular free wall. Right ventricular free wall involvement by cyst that ruptured to pericardial cavity is very rare presentation of hydatid cyst. Cardiac involvement may have serious consequences such as rupture to blood steam or pericardial cavity. Both the disease and its surgical treatment carry a high complication rate, including rupture leading to cardiac tamponade, anaphylaxis and also death. In the present report, a 43-year-old man with constrictive pericarditis secondary to a pericardial hydatid cyst is described. PMID- 26139762 TI - Diagnosis of cardiac tamponade with transesophageal echocardiography following the induction of anesthesia for suspected testicular torsion. AB - Transesophageal echocardiography (TEE) is a valuable tool for evaluating hemodynamic instability in patients under general anesthesia. We present the case of a 28-year-old man who presented with complaints of testicular pain concerning for testicular torsion. After induction of general anesthesia for scrotal exploration and possible orchiopexy, the patient developed severe and persistent hypotension. Using intraoperative TEE, the diagnosis of pericardial tamponade was made, and an emergent pericardial window was performed. PMID- 26139763 TI - Pressure bandage over venous conduit harvesting site causing compartment syndrome in a patient with intra-aortic balloon pump: An unusual cause. AB - Intra Aortic Balloon Pump (IABP) is conventionally used to support coronary perfusion and weaning from cardiopulmonary bypass. IABP in situ has its own share of complications. We present a case where a patient on IABP support who had reduced peripheral pulsations of the ipsilateral limb and was initially misdiagnosed as IABP catheter associated thromboembolism. A negative embolectomy ruled out the same. Further looking for the cause of reduction of ipsilateral pulses it was found that the tight compressive bandage at saphenous vein conduit harvesting site had led to development of compartment syndrome (CS). PMID- 26139764 TI - Understanding poor man's diseases in contemporary perspective. PMID- 26139765 TI - Haemoglobinopathies in tribal populations of India. AB - Haemoglobinopathies particularly haemoglobin S and E (HbS, HbE) and beta thalassaemia are important challenges for tribal populations in India. The HbS, HbE and beta-thalassaemia genes are variably distributed across various tribal populations of India. HbE is mainly restricted in tribals of North-East, West Bengal, Odisha and those in Andaman and Nicobar islands. HbS has more extensive distribution in the country (10-40% trait frequency) and the homozygotes and double heterozygotes present with a wide array of morbidities. The morbidity varies greatly in different areas of the country due to differential co inheritance of alpha-thalassaemia gene and interaction of various epistatic and environmental factors. Though substantial data on prevalence of these disorders exist, there is an urgent need to develop integrated hierarchical core facilities to manage the disease. Such centres will generate more data and will also explore areas of management which need more local attention. Newborn screening, genetic counselling, carrier detection, prenatal diagnosis along with management of cases should form the basic infrastructure of haemoglobinopathy management. Research in this areas should continue focusing on various challenges in care delivery, prevention and basic sciences on interaction of haemoglobinopathies with various other infections. PMID- 26139767 TI - Glucose-6-phosphate dehydrogenase (G6PD) deficiency among tribal populations of India - Country scenario. AB - It is believed that the tribal people, who constitute 8.6 per cent of the total population (2011 census of India), are the original inhabitants of India. Glucose 6-phosphate-dehydrogenase (G6PD) deficiency is an X-linked genetic defect, affecting around 400 million people worldwide and is characterized by considerable biochemical and molecular heterogeneity. Deficiency of this enzyme is highly polymorphic in those areas where malaria is/has been endemic. G6PD deficiency was reported from India more than 50 years ago. t0 he prevalence varies from 2.3 to 27.0 per cent with an overall prevalence of 7.7 per cent in different tribal groups. Since the tribal populations live in remote areas where malaria is/has been endemic, irrational use of antimalarial drugs could result in an increased number of cases with drug induced haemolysis. Therefore, before giving antimalarial therapy, routine screening for G6PD deficiency should be undertaken in those tribal communities where its prevalence is high. PMID- 26139766 TI - Sickle cell disease in tribal populations in India. AB - The sickle gene is widespread among many tribal population groups in India with prevalence of heterozygotes varying from 1-40 per cent. Co-inheritance of the sickle gene with beta-thalassaemia, HbD Punjab and glucose-6-phosphate dehydrogenase (G6PD) deficiency has also been reported. Most of the screening programmes in India now use high performance liquid chromatography (HPLC) analysis although the solubility test is also sensitive and cheap. Sickle cell disease (SCD) among tribal populations is generally milder than among non-tribal groups with fewer episodes of painful crises, infections, acute chest syndrome and need for hospitalization. This has partly been attributed to the very high prevalence of alpha-thalassaemia among these tribes as well as higher foetal haemoglobin levels. However, the clinical presentation is variable with many cases having a severe presentation. There is not much information available on maternal and perinatal outcome in tribal women with sickle cell disease. Newborn screening programmes for SCD have recently been initiated in Maharashtra, Gujarat, Orissa and Chattisgarh and monitoring these birth cohorts will help to understand the natural history of SCD in India. Prenatal diagnosis is acceptable by tribal families in India. The Indian Council of Medical Research and the National Rural Health Mission in different States are undertaking outreach programmes for better management and control of the disease. PMID- 26139768 TI - Status of HbE variant among Rabha tribe of West Bengal, India. PMID- 26139769 TI - Biology & control of Anopheles culicifacies Giles 1901. AB - Malaria epidemiology is complex due to multiplicity of disease vectors, sibling species complex and variations in bionomical characteristics, vast varied terrain, various ecological determinants. There are six major mosquito vector taxa in India, viz. Anopheles culicifacies, An. fluviatilis, An. stephensi, An. minimus, An. dirus and An. sundaicus. Among these, An. culicifacies is widely distributed and considered the most important vector throughout the plains and forests of India for generating bulk of malaria cases (>60% annually). Major malaria epidemics are caused by An. culicifaices. It is also the vector of tribal malaria except parts of Odisha and Northeastern States of India. An. culicifacies has been the cause of perennial malaria transmission in forests, and over the years penetrated the deforested areas of Northeast. An. culicifacies participates in malaria transmission either alone or along with An. stephensi or An. fluviatilis. The National Vector Borne Disease Control Programme (NVBDCP) spends about 80 per cent malaria control budget annually in the control of An. culicifacies, yet it remains one of the most formidable challenges in India. With recent advances in molecular biology there has been a significant added knowledge in understanding the biology, ecology, genetics and response to interventions, requiring stratification for cost-effective and sustainable malaria control. Research leading to newer interventions that are evidence-based, community oriented and sustainable would be useful in tackling the emerging challenges in malaria control. Current priority areas of research should include in-depth vector biology and control in problem pockets, preparation of malaria-risk maps for focused and selective interventions, monitoring insecticide resistance, cross border initiative and data sharing, and coordinated control efforts for achieving transmission reduction, and control of drug-resistant malaria. The present review on An. culicifacies provides updated information on vector biology and control outlining thrust areas of research. PMID- 26139770 TI - Malaria situation in India with special reference to tribal areas. AB - BACKGROUND & OBJECTIVES: In India, malaria is a major public health problem in States having predominantly tribal population. The objective of this analysis was to find out the incidence of malaria in various States/districts having varied proportions of tribal population using National Vector Borne Disease Control Programme (NVBDCP) data. METHODS: States and districts were classified into three categories based on proportions of Scheduled Tribes (ST) population as <10, 10 29.9 and 30 per cent + ST population. Five year average (2008-2012) of all important malaria indicators collected by NVBDCP was taken to normalize the effect of annual fluctuations in malaria incidence. RESULTS: State level analysis revealed that ten States/UTs with 30 per cent or more tribal population comprising only three per cent of total population, contributed 14 per cent of total malaria, 21 per cent Plasmodium falciparum and 29 per cent of deaths due to malaria. Similarly, district level analysis showed that districts with 30 per cent or more tribal population comprising about eight per cent country's population contributed to 46 per cent of total malaria cases, 70 per cent P. falciparum and 47 per cent malarial deaths in the country. INTERPRETATION & CONCLUSIONS: Our analysis showed that the neglect of the ethnic communities in tribal areas would be detrimental to the overall reduction of morbidity and mortality due to malaria. The fight against the increasing burden of malaria in tribal belt requires adoption of multiple approaches and socio-economic development of the tribal communities. PMID- 26139771 TI - Neglected Plasmodium vivax malaria in northeastern States of India. AB - BACKGROUND & OBJECTIVES: The northeastern States of India are co-endemic for Plasmodium falciparum and P. vivax malaria. The transmission intensity is low-to moderate resulting in intermediate to stable malaria. Malaria control prioritized P. falciparum being the predominant and life threatening infection (>70%). P. vivax malaria remained somewhat neglected. The present study provides a status report of P. vivax malaria in the northeastern States of India. METHODS: Data on spatial distribution of P. vivax from seven northeastern States (Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland and Tripura) were analysed retrospectively from 2008-2013. In addition, cross-sectional malarial surveys were conducted during 1991-2012 in malaria endemic pockets across the States of Assam, Meghalaya, Mizoram and Tripura to ascertain the prevalence of P. vivax in different age groups. RESULTS: Vivax malaria was encountered in all northeastern States but there existed a clear division of two malaria ecotypes supporting <=30 and >30 per cent of total malaria cases. High proportions of P. vivax cases (60 80%) were seen in Arunachal Pradesh and Nagaland in the north with alpine environment, 42-67 per cent in Manipur, whereas in Assam it varied from 23-31 per cent with subtropical and tropical climate. Meghalaya, Tripura and Mizoram had the lowest proportion of P. vivax cases. Malaria cases were recorded in all age groups but a higher proportion of P. vivax consistently occurred among <5 yr age group compared to P. falciparum (P<0.05). P. vivax cases were recorded throughout the year with peak coinciding with rainy season although transmission intensity and duration varied. INTERPRETATION & CONCLUSIONS: In northeast India, P. vivax is a neglected infection. Estimating the relapsing pattern and transmission dynamics of P. vivax in various ecological settings is an important pre-requisite for planning malaria elimination in the northeastern States. PMID- 26139772 TI - Transmission dynamics & epidemiology of malaria in two tribal districts in Madhya Pradesh, India. AB - BACKGROUND AND OBJECTIVES: Epidemiology and transmission of malaria vary within the tribal areas with the variation in topography, forest cover and type of forest. For the control of disease, understanding of the dynamics of transmission in the varied ecological situation is essential. This study was carried out in the two distinct tribal areas- Baiga Chak (thick forested area) of Dindori district and Bichhia block (forest fringe area) of Mandla district, Madhya Prasdesh, India, to understand the epidemiology and transmission dynamics of malaria. METHODS: Mosquitoes were collected using hand catch and whole night collections to determine the proportion of vectors, their density and seasonality. Vector incrimination was done by sporozoite ELISA and feeding preferences of vector by gel diffusion method. Active fever surveys were carried out fortnightly to determine the age specific malaria parasite rates among the inhabitants of two areas. RESULTS: Density of Anopheles culicifacies was significantly higher in Bichhia while the density of An. fluviatilis was higher in Baiga Chak. An. culicifacies was incriminated from both the areas while An. fluviatilis was incriminated from Baiga Chak only. Malaria slide positivity rate (SPR) was significantly higher (OR=3.7 95%CI, 3.1-4.4) in Baiga Chak (28.2%) than Bichhia (9.6%). INTERPRETATION & CONCLUSIONS: The features of malaria transmission in tribal areas differed from those reported in rural or semirural population. Site-specific and region-specific studies are required to develop appropriate intervention measures to control malaria. PMID- 26139773 TI - Socio-economic & household risk factors of malaria in tribal areas of Madhya Pradesh, central India. AB - BACKGROUND & OBJECTIVES: Malaria is a major public health problem in many States of the country, particularly, in Madhya Pradesh where both Plasmodium vivax and P. falciparum are endemic. Although many studies have been conducted to investigate risk factors for malaria, but only a few have examined household and socio-economic risk factors. The present study was, therefore, undertaken to explore the relationship of different socio-demographic, socio-economic and behavioural risk factors with malaria prevalence in tribal areas of Madhya Pradesh, India. METHODS: This study was undertaken in all 62 villages of Bargi Primary Health Centre from May 2005 to June 2008. These villages comprised 7117 households with an average family size of five members. Fortnightly fever surveys were conducted in all villages to assess prevalence of malaria infection in the community. The distinct univariate and multivariate logistic regression models were fitted on the data set. RESULTS: The important socio-demographic risk factors like age of household head, social group, occupation and family size; socio-economic factors like type of walls of house, place of drinking water source, irrigated land, cash crop; and behavioural variables like place of sleeping, use of bed nets, etc. were found significantly associated with malaria in univariate analyses. In multivariate analyses only social groups, family size, type of walls of house, and place of sleeping had strong significant association with prevalence of malaria. INTERPRETATION & CONCLUSIONS: The study shows that in tribal areas where people are living in poor quality of houses with no proper use of preventive measures, malaria is firmly established. We conclude that community based interventions which bring improvement in standard of living, access to healthcare facilities and health awareness, will have a significant impact on malaria prevention in these areas. PMID- 26139774 TI - Establishing communication mechanism for malaria prevention in Baiga tribal villages in Baiga Chak area of Dindori district, Madhya Pradesh. AB - BACKGROUND & OBJECTIVES: Malaria is a serious public health concern in several parts of India, particularly in tribal areas of Madhya Pradesh (MP). Dindori district inhabitated by Baiga tribe, contributes about 15 per cent to the total malaria burden in MP. The tribal and other local inhabitants believe in magico religious treatment of malaria and use modern health facilities only as second line of treatment. The present study was planned in the villages of one of the particularly vulnerable tribal group of MP, the Baigas. The objective of the study was to generate awareness and utilization of health services for malaria by establishing a communication strategy using local students and unemployed youths as agents of change. METHODS: The study was undertaken in 47 villages and the need based IEC (information, education and communication) intervention was evaluated within four months of initiation by adopting before and after with control design. For both baseline and resurvey the households covered each time were 2350. RESULTS: The baseline data generated revealed that around 53 per cent of the people in the study villages were aware of malaria. Among the non Baigas, 59 per cent were aware of malaria, while among the Baigas it was 49 per cent. IEC intervention could raise the level of awareness to malaria significantly with a net intervention effect of 23 per cent. The IEC intervention also improved the utilization of modern health services significantly. INTERPRETATION & CONCLUSIONS: The IEC strategy designed by using local children and youths was effective as the malaria was on decline in the study area. The same strategy with necessary modifications may be replicated in other areas pandemic for malaria. PMID- 26139775 TI - Emergence of dengue in tribal villages of Mandla district, Madhya Pradesh, India. AB - BACKGROUND & OBJECTIVES: Dengue (DEN) is a rapidly spreading arboviral disease transmitted by Aedes mosquitoes. Although it is endemic in India, dengue virus (DENV) infection has not been reported from tribal areas of Madhya Pradesh. Investigations were conducted to establish the aetiology of sudden upsurge of cases with febrile illness in June 2013 from tribal villages of Mandla district of Madhya Pradesh, India. METHODS: The rapid response team of the National Institute for Research in Tribal Health, Jabalpur, conducted clinical investigations and field surveys to collect the samples from suspected cases. Samples were tested using molecular and serological tools. Collected mosquitoes were identified and tested for the presence of virus using semi nested reverse transcriptase-polymerase chain reaction (nRT-PCR). The sequences were analysed to identify serotype and genotype of the virus. RESULTS: Of the 648 samples collected from 18 villages of Mandla, 321 (49.53%) were found to be positive for dengue. The nRT-PCR and sequencing confirmed the aetiology as dengue virus type 2. Eighteen per cent of patients needed hospitalization and five deaths were attributed to dengue. The virus was also detected from Aedes aegypti mosquito, which was incriminated as a vector. Phylogenetic analysis revealed that the dengue virus 2 detected belonged to cosmopolitan genotype of the virus. INTERPRETATION & CONCLUSIONS: Dengue virus serotype 2 was detected as the aetiological agent in the outbreak in tribal villages of Mandla district of Madhya Pradesh. Conducive man-made environment favouring mosquitogenic conditions and seeding of virus could be the probable reasons for this outbreak. Urgent attention is needed to control this new threat to tribal population, which is already overburdened with other vector borne diseases. PMID- 26139776 TI - Chikungunya outbreak in Garo Hills, Meghalaya: An epidemiological perspective. AB - BACKGROUND & OBJECTIVES: Chikungunya (CHIK) fever is a mosquito-borne disease caused by chikungunya virus (CHIKV). Chikungunya infection was first reported from India in 1963 from Kolkata. We report the serological and molecular evidence of an outbreak of chikungunya in northeast India that occurred in Tura, a hilly and forested terrain in Garo Hills district of Meghalaya. METHODS: Blood samples (3 ml) collected from hospitalized patients during the outbreak were tested for IgM antibodies against CHIKV and followed up four months later. A repeat survey was carried out in the same area after four months from where cases had been reported. Blood samples were also collected from people with history of fever and body ache in the last four months. Persons showing IgM positivity against CHIKV in the repeat survey were followed up one and a half years later. All samples were also processed by RT-PCR assay for CHIK Envelope (E) 1 gene. Immature mosquitoes were collected, link reared and identified with standard keys. Virus incrimination studies were done on Aedes aegypti and Ae. albopictus mosquitoes collected during the survey. RESULTS: Fever, headache and joint pain were the primary clinical presentations. Twenty three (35.93 %) of 64 samples reported during the outbreak were IgM positive for CHIK. Three samples showed PCR amplification. All these were IgM positive. The sequenced E1 gene revealed that the strains belonged to East Central South African (ECSA) genotype. INTERPRETATION & CONCLUSIONS: Field survey done after four months revealed that some individuals still had joint pain associated with episodes of headache and fever. It could be inferred that these persons might have contracted infection during the CHIK outbreak four months ago or during the intervening period which caused persistence of sequelae. ECSA genotype was found to be involved in the outbreak. Aedes albopictus was the predominant mosquito species collected during the outbreak. PMID- 26139777 TI - Diurnally subperiodic filariasis among the Nicobarese of Nicobar district - epidemiology, vector dynamics & prospects of elimination. AB - In India diurnally subperiodic filariasis (DspWB) is prevalent only in the Nicobar district of Andaman and Nicobar Islands. Studies undertaken at different points of time indicate that this form of filariasis is restricted to a small region in Nancowry group of islands where it is transmitted by mosquito Downsiomyia nivea, a day biting mosquito. Studies on prevalence, distribution, and assessment of endemicity status, vector incrimination, bioecology, host seeking behaviour, population dynamics of the vector, transmission dynamics and clinical epidemiology indicate the prevalence and persistence of this infection in the Nancowry group of islands with perennial transmission. There was no control programme in these islands, until the National programme to eliminate filariasis was launched in 2004. Eight rounds of annual mass drug administration (MDA) with diethyl carbamazine (DEC) + albendazole have been completed. Despite this, microfilaria prevalence remains at above one per cent, the level identified for initiating transmission assessment survey to decide on continuation of MDA further. This necessitates adjunct measures to the ongoing MDA programme in these islands. The vector control options could be an adjunct measure, but the vector is a forest dweller with a unique bio-ecology, therefore, not a technically feasible option. Use of DEC fortified salt for six months to one year could hasten the process of elimination. Although administration of DEC-fortified salt is simple, rapid, safe, and cost-effective, challenges are to be tackled for evolving operationally realistic strategy. Such a strategy requires commitment of all sections of the society, a distribution mechanism that ensures the use of DEC fortified salt in the Nancowry islands. Here we discuss the plan of action to serve the indigenous communities and operationalizing DEC fortified salt strategy through an inter-sectoral approach involving multiple stakeholders. PMID- 26139778 TI - Eradicating successfully yaws from India: The strategy & global lessons. AB - Yaws, a non-venereal treponematosis, affecting primarily the tribal populations, has been considered historically as one of the most neglected tropical diseases in the world. In 1996, India piloted an initiative to eradicate yaws based on a strategy consisting of active case finding through house-to-house search and treatment of cases and their contacts with long acting penicillin. Thereafter, the campaign implemented in all 51 endemic districts in 10 states of the country led to the achievement of a yaws-free status in 2004. In the post-elimination phase, surveillance activities accompanied by serological surveys were continued in the erstwhile endemic districts. These surveys carried out among children between the age of 1-5 yr, further confirmed the absence of community transmission in the country. The experience of India demonstrates that yaws can be eradicated in all endemic countries of Africa and Asia, provided that political commitment can be mobilized and community level activities sustained until the goal is achieved. PMID- 26139779 TI - Pulmonary tuberculosis among tribals in India: A systematic review & meta analysis. AB - BACKGROUND & OBJECTIVES: There has been limited investigation on the prevalence of tuberculosis (TB) in tribal communities in India, a vulnerable section of Indian society. The lack of a population-based estimate prompted us to conduct a meta-analysis of existing studies to provide a single, population-based estimate of the TB prevalence for tribals. METHODS: Literature search was conducted in PubMed using the keywords - "tuberculosis", "tribals", "India", "prevalence", and "survey". References cited in the articles retrieved were also reviewed, and those found relevant were selected. TB prevalence rates estimated by the studies were used for our calculation of a pooled-estimate. RESULTS: The pooled estimate, based on the random effects model, was 703 per 100,000 population with a 95 % CI of 386-1011. The associated heterogeneity measures in terms of Cochran's Q was significant ( p=0 0.08 <0.1) and I [2] was moderate at 48 per cent. INTERPRETATION & CONCLUSIONS: The meta-analysis demonstrated a large variability in pulmonary TB prevalence estimates among the different studies with poor representation of the various tribal groups. The moderate level of heterogeneity found across the studies suggests that the pooled-estimate needs to be treated with caution. Our findings also highlight the need to assess the pulmonary TB burden in India. PMID- 26139780 TI - Performance of Revised National Tuberculosis Control Programme (RNTCP) in tribal areas in India. AB - BACKGROUND & OBJECTIVES: The Revised National Tuberculosis Control Programme (RNTCP) provides free diagnostic and treatment services to all tuberculosis (TB) patients registered under it. Equitable access, implying a preference for the most hard-to-reach groups particularly for tribal areas, is a major concern for RNTCP. This study was conducted to assess the performance of RNTCP in terms of case detection and cure rates in areas dominated by tribal groups in India. METHODS: We used the RNTCP data collected by the Central TB Divison, Government of India. RNTCP has a systematic monitoring mechanism which tracks the outcome of every patient put on treatment. There is a standardized recording and reporting structure in place; indicators are monitored regularly at every level of the health system; and regular supervision ensures quality of the Programme. The main indicators include the number of cases diagnosed and the percentage of patients who are successfully treated. These indicators were used to assess the RNTCP performance in tribal areas. RESULTS: We observed a poor performance in terms of case detection rate (CDR) in tribal and backward districts as compared with other districts in India. Among tribal districts 53 per cent in 2010, 45 per cent in 2011 and 56 per cent in 2012 had CDR of new smear positive <70%. It was also observed that 26 per cent of tribal dominated districts had CDR of <51 per cent in 2012. More than 50 per cent of tribal districts were not able to achieve more than 85 per cent of cure rate. INTERPRETATION & CONCLUSIONS: The findings of this study suggested that the overall RNTCP performance in tribal areas was not optimal, and the target of >85 per cent of core rate was achieved by less than half of the tribal districts. PMID- 26139781 TI - Pulmonary tuberculosis - a health problem amongst Saharia tribe in Madhya Pradesh. AB - BACKGROUND & OBJECTIVES: The information on tuberculosis (TB) situation amongst Saharia, one of the particularly vulnerable tribal groups (PVTGs) in Madhya Pradesh, is not available from Gwalior division of the s0 tate. Hence, this study was undertaken to estimate the prevalence of pulmonary tuberculosis (PTB) disease amongst them. METHODS: A community based cross-sectional TB prevalence survey was undertaken among Saharia PVTG in Gwalior district of Madhya Pradesh. A random sample of villages predominated by Saharia tribe was selected from all the blocks in proportion to the size of Saharia population in each block of the district. All eligible individuals were questioned for chest symptoms relating to TB. Two sputum samples were collected from each of the eligible individuals, transported to the laboratory, and were examined by Ziehl-Neelsen(ZN) smear microscopy and solid media culture methods. RESULTS: Of the total 10,259 individuals eligible for screening, 9,653 (94.1%) were screened for symptoms. Overall prevalence of PTB was found to be 3294 per 100,000. The prevalence increased with age and the trend was significant ( p<0.001). The prevalence of TB was significantly higher amongst males (5497/100,000) as compared to females (1376/100,000) ( p<0.001). INTERPRETATION & CONCLUSIONS: The study results provide vital information on the current situation of pulmonary TB disease among the Saharia tribal community in Gwalior district of Madhya Pradesh. In view of high PTB disease prevalence among this PVTG, there is an urgent need to improve and further intensify TB control measures in this area. PMID- 26139782 TI - Situation of drug resistant tuberculosis in Saharia tribe of central India. AB - BACKGROUND & OBJECTIVES: The information on multidrug resistant tuberculosis (MDR TB) situation amongst Saharia, one of the Particularly Vulnerable Tribal Groups (PVTGs) in Madhya Pradesh, India, is not available. Hence, this study was undertaken to find the situation of MDR-TB amongst Saharia PVTG in two districts of Madhya Pradesh. METHODS: Community based cross-sectional TB prevalence surveys were conducted among Saharia PVTG in Gwalior and Shivpuri districts of Madhya Pradesh. Chest symptomatics were identified from the individual registered for the study. Two sputum samples were collected from each of the eligible individuals, transported to the laboratory, and were examined by Ziehl-Neelsen (Z N) smear microscopy and solid medium culture methods. Drug susceptibility testing of the isolates was done by indirect proportion method on solid medium. RESULTS: MDR rate was 2.2 per cent of new cases and 8.2 per cent among the previously treated cases of TB in Gwalior while it was two per cent among the previously treated cases in Shivpuri district. INTERPRETATION & CONCLUSIONS: Though the prevalence of tuberculosis in these districts was alarmingly high, the MDR rates were more or less similar to national average. However, the findings of this study highlight the need for active intervention so that the MDR-TB is kept under control. PMID- 26139783 TI - Health literacy on tuberculosis amongst vulnerable segment of population: special reference to Saharia tribe in central India. AB - BACKGROUND & OBJECTIVES: Health literacy on tuberculosis (TB) is an understanding about TB to perform activities with regard to prevention, diagnosis and treatment. We undertook a study to assess the health literacy on TB among one of the vulnerable tribal groups (Saharia) in central India. METHODS: In this cross sectional study, 2721 individuals aged >15 yr from two districts of Madhya Pradesh State of India were interviewed at their residence during December 2012 July 2013. By using a short-form questionnaire, health literacy on cause, symptoms, mode of transmission, diagnosis, treatment and prevention of TB was assessed. RESULTS: Of the 2721 (Gwalior 1381; Shivpuri 1340) individuals interviewed; 76 per cent were aged <45 yr. Living condition was very poor (62% living in huts/katcha houses, 84 per cent with single room, 89 per cent no separate kitchen, 97 per cent used wood/crop as a fuel). Overall literacy rate was 19 per cent, and 22 per cent had >7 members in a house. Of the 2721 respondents participated, 52 per cent had never heard of TB; among them 8 per cent mentioned cough as a symptom, 64 per cent mentioned coughing up blood, and 91 per cent knew that TB diagnosis, and treatment facilities were available in both government and private hospitals. Health literacy score among participants who had heard of TB was <40 per cent among 36 per cent of respondents, 41-60 per cent among 54 per cent and >60 per cent among 8 per cent of respondents. INTERPRETATION & CONCLUSIONS: The finding that nearly half of the respondents had not heard of TB indicated an important gap in education regarding TB in this vulnerable population. There is an urgent need to implement targeted interventions to educate this group for better TB control. PMID- 26139784 TI - Declining prevalence of pulmonary paragonimiasis following treatment & community education in a remote tribal population of Arunachal Pradesh, India. AB - BACKGROUND & OBJECTIVES: In India, human pulmonary paragonimiasis is an important public health problem in the northeastern (NE) region. In 2005 we reported a hyperendemic focus of paragonimiasis in a remote tribal village in the hills of Changlang district in Arunachal Pradesh. The community was made aware of the disease and all active cases were treated. This study was aimed to assess the decline in the prevelance of paragonimiasis in the same area after a re-survey done in 2011 after a gap of six years. METHODS: Re-surveys were carried to determine the reduction in the prevalence of paragonimiasis. Community education was given to the villagers to raise their awareness about paragonimiasis. A total of 624 individuals including 301 children (age 15 yr) were included in the study. Sputum and stool samples were examined for eggs of lung flukes. Serum samples were screened for IgG antibodies against lung fluke antigen by ELISA. RESULTS: A significant (P<0.001) decline in the prevalence of paragonimiasis was found. There was decline in both ELISA positivity and egg positivity. Antibody positivity against excretory-secretary (ES) antigen in children (age 15 yr) fell down from earlier 51.7 to 15.9 per cent and in individuals 16 - 30 yr of age the serological prevalence fell down from 22.4 to 8.2 per cent and in individuals aged th > 31 yr, the decline in prevalence was from 15.3 to 3.7 per cent. Gender wise analysis revealed that the decline in ELISA positivity was similar in both genders and fell down from 33.9 to 11.5 per cent in males and from 29.8 to 10.7 per cent in females. Similarly, there was a significant decline rate in egg positivity also. INTERPRETATION & CONCLUSIONS: The strategy of hotspot targeted active paragonimiasis case detection and treatment of infected cases together with community education appears to be feasible methods to achieve control of paragonimiasis in this region. PMID- 26139786 TI - Hepatitis B vaccination among the Nicobarese tribe: Need to document the impact. PMID- 26139785 TI - Status of hepatitis B infection - a decade after hepatitis B vaccination of susceptible Nicobarese, an indigenous tribe of Andaman & Nicobar (A&N) islands with high hepatitis B endemicity. AB - BACKGROUND & OBJECTIVES: Andaman and Nicobar Islands of India, home to six primitive tribes, constituting about 10 per cent of the total population of these Islands have been detected with high endemicity of hepatitis B infection. During 2000, a total of 936 individuals <= 45 yr, negative for hepatitis B surface antigen (HBsAg) and antibody anti-HBs were vaccinated with three doses of a recombinant DNA hepatitis B vaccine in two villages of Car Nicobar Islands. The present study was undertaken to evaluate the impact of the hepatitis B vaccination with respect to the persistence of antibodies and incidence of new infections, prevalence of surface gene mutations among the Nicobarese community in the two villages ten years after hepatitis B vaccination. METHODS: Follow up samples were collected from 211 individuals who had received three doses of vaccine ten years back and from a control group of 515 non-vaccinated individuals. The HBsAg, anti-HBs and anti-HBc assay results were compared among vaccinated and non-vaccinated groups. HBV DNA was extracted and sequenced from all the samples for detection of mutation. Genotyping and serotyping of the viruses were performed. RESULTS: The results showed that 85.3 per cent of the vaccinated persons retained protective level of antibodies and among the non vaccinated individuals, 54.2 per cent showed presence of anti-HBs indicating an exposure to the infection. The overall HBsAg positivity among the studies Nicobarese individuals was reduced to 7.4 per cent after 10 years of vaccination. Anti-HBc was positive in 60.6 and 57 per cent among the vaccinated and non vaccinated individuals, respectively. Overall breakthrough infection of 8.5 per cent was detected among the vaccinated individuals. The predominant genotype and serotype circulating among these tribal populations were D and ayw3, respectively. INTERPRETATION & CONCLUSIONS: The results of this study showed an overall reduction in the pool of HBsAg carriers because of the vaccination which helped in reducing the HBsAg carrier rate among the non-vaccinated also, probably due to an increase in herd immunity and reduction in the source of infection. Further studies need to be done to evaluate long term benefits of hepatitis B vaccination among these tribes. PMID- 26139787 TI - Burden & pattern of illnesses among the tribal communities in central India : A report from a community health programme. AB - Tribals are the most marginalised social category in the country and there is little and scattered information on the actual burden and pattern of illnesses they suffer from. This study provides information on burden and pattern of diseases among tribals, and whether these can be linked to their nutritional status, especially in particularly vulnerable tribal groups (PVTG) seen at a community health programme being run in the tribal areas of Chhattisgarh and Madhya Pradesh States of India. This community based programme, known as Jan Swasthya Sahyog (JSS) has been serving people in over 2500 villages in rural central India. It was found that the tribals had significantly higher proportion of all tuberculosis, sputum positive tuberculosis, severe hypertension, illnesses that require major surgery as a primary therapeutic intervention and cancers than non tribals. The proportions of people with rheumatic heart disease, sickle cell disease and epilepsy were not significantly different between different social groups. Nutritional levels of tribals were poor. Tribals in central India suffer a disproportionate burden of both communicable and non communicable diseases amidst worrisome levels of undernutrition. There is a need for universal health coverage with preferential care for the tribals, especially those belonging to the PVTG. Further, the high level of undernutrition demands a more augmented and universal Public Distribution System. PMID- 26139788 TI - Tribes in Karnataka: Status of health research. AB - The south Indian State of Karnataka, once part of several kingdoms and princely states of repute in the Deccan peninsula, is rich in its historic, cultural and anthropological heritage. The State is the home to 42,48,987 tribal people, of whom 50,870 belong to the primitive group. Although these people represent only 6.95 per cent of the population of the State, there are as many as 50 different tribes notified by the Government of India, living in Karnataka, of which 14 tribes including two primitive ones, are primarily natives of this State. Extreme poverty and neglect over generations have left them in poor state of health and nutrition. Unfortunately, despite efforts from the Government and non Governmental organizations alike, literature that is available to assess the state of health of these tribes of the region remains scanty. It is however, interesting to note that most of these tribes who had been original natives of the forests of the Western Ghats have been privy to an enormous amount of knowledge about various medicinal plants and their use in traditional/folklore medicine and these practices have been the subject matter of various scientific studies. This article is an attempt to list and map the various tribes of the State of Karnataka and review the studies carried out on the health of these ethnic groups, and the information obtained about the traditional health practices from these people. PMID- 26139789 TI - Diet & nutrition profile of Chenchu population - A vulnerable tribe in Telangana & Andhra Pradesh, India. AB - BACKGROUND & OBJECTIVES: Earlier studies have documented high prevalence of undernutrition, morbidity and mortality among Chenchus, a tribal population in Telangana and Andhra Pradesh, India. The present study was carried out to assess diet and nutritional status of Chenchus and cause of death. METHODS: A total of 42 Chenchu villages (gudems) were covered using systematic random sampling procedure. In each gudem, all the households with at least one child under the age of five years were covered for various investigations. Weighment diet survey was carried out on a sub-sample of households. In addition, information on cause of death in the selected 42 gudems was collected for past one year using verbal autopsy method. RESULTS: A total of 1396 subjects of all age groups were covered for various investigations. The intakes of food and nutrients were lower than the recommended levels. The prevalences of underweight, stunting and wasting among under five children were 42 per cent (CI: 37.9-46.1), 53 and 13 per cent, respectively, while 41 per cent (CI: 37.8-47.2) men and 42 per cent (34.4-47.8) women had chronic energy deficiency (BMI<18.5 kg/m [2] ). Sixty eight deaths were reported during the past one year in 42 Chenchu gudems. The major causes of death were premature delivery, low birth weight, alcoholic cirrhosis of liver, accidents, snakebite and pulmonary tuberculosis. INTERPRETATION & CONCLUSIONS: The prevalence of undernutrition in Chenchu population was comparable with other tribal and rural counterparts in Andhra Pradesh, however, the crude death rate (11.7/1000) was higher among the Chenchus. Steps may be taken to promote consumption of balanced diet and utilization of optimal healthcare facilities to control morbidity and mortality. PMID- 26139790 TI - Socio-economic & demographic determinants of hypertension & knowledge, practices & risk behaviour of tribals in India. AB - BACKGROUND & OBJECTIVES: An increase in prevalence of hypertension has been observed in all ethnic groups in India. The objective of the present study was to estimate prevalence and determinants of hypertension among tribals and their awareness, treatment practices and risk behaviours in nine States of India. METHODS: A community based cross-sectional study adopting multistage random sampling procedure was carried out. About 120 Integrated Tribal Development Authority villages were selected randomly from each State. From each village, 40 households were covered randomly. All men and women >= 20 yr of age in the selected households were included for various investigations. RESULTS: A total of 21141 men and 26260 women participated in the study. The prevalence of hypertension after age adjustment was 27.1 and 26.4 per cent among men and women, respectively. It was higher in the s0 tates of Odisha (50-54.4%) and Kerala (36.7 45%) and lowest in Gujarat (7-11.5%). The risk of hypertension was 6-8 times higher in elderly people and 2-3 times in 35-59 yr compared with 20-34 yr. Only <10 per cent of men and women were known hypertensives and more than half on treatment (55-68%). Men with general and abdominal obesity were at 1.69 (CI: 1.43 2.01) and 2.42 (CI: 2.01-2.91) times higher risk of hypertension, respectively, while it was 2.03 (CI=1.77-2.33) and 2.35 (CI 2.12-2.60) times higher in women. Those using tobacco and consuming alcohol were at a higher risk of hypertension compared with the non users. INTERPRETATION & CONCLUSIONS: The study revealed high prevalence of hypertension among tribals in India. Age, literacy, physical activity, consumption of tobacco, alcohol and obesity were significantly associated with hypertension. Awareness and knowledge about hypertension and health seeking behaviour were low. Appropriate intervention strategies need to be adopted to increase awareness and treatment practices of hypertension among tribals. PMID- 26139791 TI - Levels, trends & predictors of infant & child mortality among Scheduled Tribes in rural India. AB - BACKGROUND & OBJECTIVES: The level of infant and child mortality is high among Scheduled Tribes particularly those living in rural areas. This study examines levels, trends and socio-demographic factors associated with infant and child mortality among Scheduled Tribes in rural areas. METHODS: Data from the three rounds of the National Family Health Survey (NFHS) of India from 1992 to 2006 were analysed to assess the levels and trends of infant and child mortality. Univariate and multivariate Cox proportional hazard model were used to understand the socio-economic and demographic factors associated with mortality during 1992 2006. RESULTS: Significant change was observed in infant and child mortality over the time period from 1992-2006 among Scheduled Tribes in rural areas. After controlling for other factors, birth interval, household wealth, and region were found to be significantly associated with infant and child mortality. Hazard of infant mortality was highest among births to mothers aged 30 yr or more (HR=1.3, 95% CI=1.1-1.7) as compared with births to the mother's aged 20-29 yr. Hazard of under-five mortality was 42 per cent (95% CI=1.3-1.6) higher among four or more birth order compared with the first birth order. The risk of infant dying was higher among male children (HR = 1.2, 95% CI=1.1-1.4) than among female children while male children were at 30 per cent (HR=0.7, 95% CI=0.6-0.7) less hazard of child mortality than female children. Literate women were at 40 per cent (HR=0.6, 95% CI=0.50-0.76) less hazard of child death than illiterate women. INTERPRETATION & CONCLUSIONS: Mortality differentials by socio-demographic and economic factors were observed over the time period (1992-2006) among Scheduled Tribes (STs) in rural India. Findings support the need to focus on age at first birth and spacing between two births. PMID- 26139792 TI - Herbal medicine & healthcare practices among Nicobarese of Nancowry group of Islands - an indigenous tribe of Andaman & Nicobar Islands. AB - BACKGROUND & OBJECTIVES: Tribal people often depend on herbal medicines and the traditional knowledge practitioners (TKPs) serve as their healthcare service providers. This study was an attempt to document the use of medicinal plants by the Nicobarese of Nancowry group of Islands. METHODS: Field survey was conducted in all the five inhabited Islands of the Nancowry group of Islands. All the TKPs were interviewed with a questionnaire-guided ethnomedicinal survey protocol. Voucher specimens of all the cited plants (botanic species) were collected and a Community Biodiversity Register of Nicobarese of Nancowry was prepared. RESULTS: A total of 77 TKPs were identified, who together were using 132 medicinal plant species belonging to 113 genera and 62 families. The TKPs were treating a total of 43 ailments. Seven endemic and three rare plant species were recorded. The most common plant part used was leaves. Remedies were usually prepared using water as the excipient. Routes for administration of medicinal plant preparations were oral, topical and others. The information collected from the TKPs were collated in the form of Community Biodiversity Registers. INTERPRETATION & CONCLUSIONS: The present survey shows that the medicinal plants play a pivotal role in the healthcare of the Nicobarese tribe of Nancowry group of Islands. Efforts to document the medicinal plant species and the formulations used by them are necessary to prevent the loss of this precious knowledge. PMID- 26139793 TI - Beyond the horizons. PMID- 26139794 TI - Future in retinal imaging for clinicians. PMID- 26139795 TI - Look what else we found--clinically significant abnormalities detected during routine ROP screening. AB - PURPOSE: The purpose of this study was to report the spectrum of anterior and posterior segment diagnoses in Asian Indian premature infants detected serendipitously during routine retinopathy of prematurity (ROP) screening during a 1 year period. METHODS: A retrospective review of all Retcam (Clarity MSI, USA) imaging sessions during the year 2011 performed on infants born either <2001 g at birth and/or <34.1 weeks of gestation recruited for ROP screening was performed. All infants had a minimum of seven images at each session, which included the dilated anterior segment, disc, and macula center and the four quadrants using the 130 degrees lens. RESULTS: Of the 8954 imaging sessions of 1450 new infants recruited in 2011, there were 111 (7.66%) with a diagnosis other than ROP. Anterior segment diagnoses seen in 31 (27.9%) cases included clinically significant cataract, lid abnormalities, anophthalmos, microphthalmos, and corneal diseases. Posterior segment diagnoses in 80 (72.1%) cases included retinal hemorrhages, cherry red spots, and neonatal uveitis of infective etiologies. Of the 111 cases, 15 (13.5%) underwent surgical procedures and 24 (21.6%) underwent medical procedures; importantly, two eyes with retinoblastoma were detected which were managed timely. CONCLUSIONS: This study emphasizes the importance of ocular digital imaging in premature infants. Visually significant, potentially life-threatening, and even treatable conditions were detected serendipitously during routine ROP screening that may be missed or detected late otherwise. This pilot data may be used to advocate for a possible universal infant eye screening program using digital imaging. PMID- 26139796 TI - En-face optical coherence tomography in the diagnosis and management of age related macular degeneration and polypoidal choroidal vasculopathy. AB - Optical coherence tomography (OCT) is a noninvasive imaging modality providing high-resolution images of the central retina that has completely transformed the field of ophthalmology. While traditional OCT has produced longitudinal cross sectional images, advancements in data processing have led to the development of en-face OCT, which produces transverse images of retinal and choroidal layers at any specified depth. This offers additional benefit on top of longitudinal cross sections because it provides an extensive overview of pathological structures in a single image. The aim of this review was to discuss the utility of en-face OCT in the diagnosis and management of age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). En-face imaging of the inner segment/outer segment junction of retinal photoreceptors has been shown to be a useful indicator of visual acuity and a predictor of the extent of progression of geographic atrophy. En-face OCT has also enabled high-resolution analysis and quantification of pathological structures such as reticular pseudodrusen (RPD) and choroidal neovascularization, which have the potential to become useful markers for disease monitoring. En-face Doppler OCT enables subtle changes in the choroidal vasculature to be detected in eyes with RPD and AMD, which has significantly advanced our understanding of their pathogenesis. En-face Doppler OCT has also been shown to be useful for detecting the polypoid lesions and branching vascular networks diagnostic of PCV. It may therefore serve as a noninvasive alternative to fluorescein and indocyanine green angiography for the diagnosis of PCV and other forms of the exudative macular disease. PMID- 26139797 TI - Clinical applications of choroidal imaging technologies. AB - Choroid supplies the major blood supply to the eye, especially the outer retinal structures. Its understanding has significantly improved with the advent of advanced imaging modalities such as enhanced depth imaging technique and the newer swept source optical coherence tomography. Recent literature reports the findings of choroidal changes, quantitative as well as qualitative, in various chorioretinal disorders. This review article describes applications of choroidal imaging in the management of common diseases such as age-related macular degeneration, high myopia, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. This article briefly discusses future directions in choroidal imaging including angiography. PMID- 26139798 TI - Choroidal thickness profile in inherited retinal diseases in Indian subjects. AB - PURPOSE: To evaluate changes in choroidal thickness (CT) in inherited retinal diseases and its relationship with age, spherical equivalent, visual acuity, and macular thickness. METHODS: Retrospective analysis of 51 eyes with features of retinal dystrophy of 26 subjects, who underwent enhanced depth imaging using spectral domain (SD) optical coherence tomography (OCT), were included. The CT measurements were made at the fovea and at 5 points with an interval of 500 microns in both directions, nasal and temporal from the fovea and were compared with age-matched healthy subjects. Step-wise regression was used to find the relationship between age, spherical equivalent, best-corrected visual acuity (BCVA), central macular thickness (CMT), and subfoveal CT. RESULTS: Disease distribution was as follows: Stargardt's disease 18 eyes (9 subjects); Best disease 5 eyes (3 subjects); cone-rod dystrophy 26 eyes (13 subjects); and Bietti's crystalline dystrophy 2 eyes (1 subject). Mean subfoveal CT was 266.33 +/- 76 microns. On regression analysis, no significant correlation was found between subfoveal CT and any other variable such as age (P = 0.9), gender (P = 0.5), CMT (P = 0.1), spherical equivalent (P = 0.3) and BCVA (P = 0.6). While comparing with age-matched healthy subjects, no significant statistical difference was noted (P < 0.05) among all age groups. CONCLUSION: Our study reports quantitative changes in CT in various common inherited retinal diseases seen in Indian populations. To validate changes in choroid, a longitudinal study with larger sample size is warranted. PMID- 26139800 TI - Microscope-integrated optical coherence tomography: A new surgical tool in vitreoretinal surgery. AB - Optical coherence tomography (OCT) has revolutionized imaging of ocular structures and various disease conditions. Though it has been used in the clinic for some decades, the OCT has only recently found its way into the operating theater. Early attempts at intraoperative OCT, hand-held and microscope mounted, have already improved our understanding of the surgical pathology and the role it might play in surgical decision-making. The microscope-integrated OCT now allows seamless, high-resolution, real-time imaging of surgical maneuvers from the incision to wound closure. Visualization of instruments and intraoperative tissue manipulation are possible with this in vivo modality and, therefore, help improve the outcome of surgery. In this article, we describe the advantages it offers during various vitreoretinal procedures. PMID- 26139799 TI - Multimodality imaging in macular telangiectasia 2: A clue to its pathogenesis. AB - Macular telangiectasia type 2 also known as idiopathic perifoveal telangiectasia and juxtafoveolar retinal telangiectasis type 2A is an acquired bilateral neurodegenerative macular disease that manifests itself during the fifth or sixth decades of life. It is characterized by minimal dilatation of the parafoveal capillaries with graying of the retinal area involved, a lack of lipid exudation, right-angled retinal venules, refractile deposits in the superficial retina, hyperplasia of the retinal pigment epithelium, foveal atrophy, and subretinal neovascularization (SRNV). Our understanding of the disease has paralleled advances in multimodality imaging of the fundus. Optical coherence tomography (OCT) images typically demonstrate the presence of intraretinal hyporeflective spaces that are usually not related to retinal thickening or fluorescein leakage. The typical fluorescein angiographic (FA) finding is a deep intraretinal hyperfluorescent staining in the temporal parafoveal area. With time, the staining may involve the whole parafoveal area but does not extend to the center of the fovea. Long-term prognosis for central vision is poor, because of the development of SRNV or macular atrophy. Its pathogenesis remains unclear but multimodality imaging with FA, spectral domain OCT, adaptive optics, confocal blue reflectance and short wave fundus autofluorescence implicate Muller cells and macular pigment. Currently, there is no known treatment for this condition. PMID- 26139801 TI - The role of central reading centers--current practices and future directions. AB - Central reading centers (CRCs) have several crucial roles in the conduct of clinical trials, providing key input during the study design, preparation of the operations manual, as well as site and photographer certification. They provide objective, standardized grading of images from study subjects, which determines study eligibility, and also evaluate lesion features at subsequent study visits. CRCs need to adhere strictly to Good Clinical Practice (GCP) guidelines, as well as the established standard operating procedures in order to ensure that images are graded properly. The role of CRCs will continue to evolve, and include the use of web-based image transmission and grading platforms. PMID- 26139803 TI - Spectral domain optical coherence tomography changes following intravitreal dexamethasone implant, Ozurdex(r) in patients with uveitic cystoid macular edema. AB - PURPOSE: To correlate the structural and functional changes following intravitreal injection of dexamethasone 0.7 mg (Ozurdex(r)) implant in patients with recalcitrant uveitic cystoid macular edema (CME). MATERIALS AND METHODS: In a prospective, interventional, nonrandomized study, 30 eyes (27 patients) with uveitic CME received Ozurdex(r) implant and were followed-up for 24 weeks at periodic intervals to monitor structural alterations seen on spectral domain optical coherence tomography (SD-OCT). The outcome measures included change in central macular thickness (CMT) and best-corrected visual acuity (BCVA) as well as structural alterations seen on OCT such as change in the height of cystoid spaces (CSs) and sub-foveal serous retinal detachment (SSRD). The integrity of external limiting membrane and inner-outer segment junction was assessed at baseline and follow-up visits. RESULTS: Mean age of the patients was 46.09 +/- 15.66 years. The mean CMT decreased by 96 MUm at 1-day, 231.64 MUm at 1-week, 254.21 MUm at 4 weeks and 249.14 MUm at 12 weeks (P < 0.001) compared with baseline. BCVA improved from a baseline mean of 0.62 LogMAR units to 0.49 on day 1 to 0.31 at 24 weeks (P < 0.001). A decrease in the mean height of CS, that is, 133.28 MUm from a baseline of 317.71 MUm was noted on the 1 st day (P < 0.001). 4 eyes demonstrated the presence of CS at 4 weeks, 1 eye at 6 weeks and 3 eyes at 12 weeks. At baseline, 16 eyes (53.33%) demonstrated the presence of SSRD. Among these, 11 eyes showed resolution of SSRD on day 1. SSRD resolved in all patients at 4 weeks and was maintained up to 24 weeks. CONCLUSIONS: Ozurdex(r) implant improves the visual outcome of patients with recalcitrant uveitic CME. Reversibility of retinal changes may be possible following treatment with dexamethasone implant. Thus final visual outcome may be independent of pretreatment CMT, the height of CS or SSRD. PMID- 26139802 TI - Fundus autofluorescence applications in retinal imaging. AB - Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID- 26139804 TI - Axial length and cone density as assessed with adaptive optics in myopia. AB - AIM: To assess the variations in cone mosaic in myopia and its correlation with axial length (AL). SUBJECTS AND METHODS: Twenty-five healthy myopic volunteers underwent assessment of photoreceptors using adaptive optics retinal camera at 2 degrees and 3 degrees from the foveal center in four quadrants superior, inferior, temporal and nasal. Data was analyzed using SPSS version 17 (IBM). Multivariable regression analysis was conducted to study the relation between cone density and AL, quadrant around the fovea and eccentricity from the fovea. RESULTS: The mean cone density was significantly lower as the eccentricity increased from 2 degrees from the fovea to 3 degrees (18,560 +/- 5455-16,404 +/ 4494/mm 2 respectively). There was also a statistically significant difference between four quadrants around the fovea. The correlation of cone density and spacing with AL showed that there was a significant inverse relation of AL with the cone density. CONCLUSION: In myopic patients with good visual acuity cone density around the fovea depends on the quadrant, distance from the fovea as well as the AL. The strength of the relation of AL with cone density depends on the quadrant and distance. PMID- 26139805 TI - Effect of ocular magnification on macular measurements made using spectral domain optical coherence tomography. AB - AIM: The aim of the present study was to study the effect of ocular magnification on macular measurements made using spectral domain optical coherence tomography (OCT). MATERIALS AND METHODS: One hundred and fifty-one subjects were included from the normative study of foveal morphology carried out at our hospital. Subjects underwent comprehensive eye examination and macular scanning using Cirrus high-definition OCT and axial length (AXL) measurement. Macular cube 512 * 128 scan protocol was used for scanning the macula. Automated measurements of the fovea namely foveal diameter, foveal slope (lateral measurements) and foveal depth (axial measurement) were taken. A correction factor for ocular magnification was done using the formula t = p * q * s, where "t0" is the corrected measurement, "p" is the magnification of OCT, "q0" is the ocular magnification, and "s" is the measurement on OCT without correction. The difference between corrected and uncorrected measurements was evaluated for statistical significance. RESULTS: Mean AXL was 22.95 +/- 0.78 mm. Refractive error ranged from -3D to +4D. Mean difference between measured and corrected foveal diameter, slope and depth was 166.05 +/- 95.37 ?m (P < 0.001), 0.81 degrees +/- 0.53 degrees (P < 0.001) and 0.05 +/- 0.49 ?m (P = 0.178) respectively. AXL lesser than the OCT calibrated value of 24.46 mm showed an increased foveal diameter (r = 0.961, P < 0.001) and a reduced foveal slope (r = 0.863, P < 0.001) than the corrected value. CONCLUSION: Lateral measurements made on OCT varied with AXL s other than the OCT calibrated value of 24.46 mm. Therefore, to estimate the actual dimensions of a retinal lesion using OCT, especially lateral dimensions, we recommend correction for the ocular magnification factor. PMID- 26139806 TI - Macular edema in Asian Indian premature infants with retinopathy of prematurity: Impact on visual acuity and refractive status after 1-year. AB - PURPOSE: To report the impact of transient, self-resolving, untreated "macular edema" detected on spectral domain optical coherence tomography in Asian Indian premature infants with retinopathy of prematurity (ROP) on visual acuity (VA) and refraction at 1-year of corrected age. MATERIALS AND METHODS: Visual acuity and refraction of 11 infants with bilateral macular edema (Group A) was compared with gestational age-matched 16 infants with ROP without edema (Group B) and 17 preterms infants without ROP and without edema (Group C) at 3, 6, 9 and 12 months of corrected age using Teller Acuity Cards and cycloplegic retinoscopy. Sub-group analysis of the previously described pattern A and B macular edema was performed. RESULTS: Visual acuity was lower in infants with macular edema compared with the other two control groups throughout the study period, but statistically significant only at 3 months. Visual improvement in these infants was highest between the 3 rd and 6 th month and plateaued by the end of the 1 st year with acuity comparable to the other two groups. The edema cohort was more hyperopic compared to the other two groups between 3 and 12 months of age. Pattern A edema had worse VA compared to pattern B, although not statistically significant. CONCLUSION: Macular edema, although transient, caused reduced VA as early as 3 months of corrected age in Asian Indian premature infants weighing <2000 g at birth. The higher hyperopia in these infants is possibly due to visual disturbances caused at a critical time of fovealization. We hypothesize a recovery and feedback mechanism based on the principles of active emmetropization to explain our findings. PMID- 26139807 TI - Positional accommodative intraocular lens power error induced by the estimation of the corneal power and the effective lens position. AB - PURPOSE: To evaluate the predictability of the refractive correction achieved with a positional accommodating intraocular lenses (IOL) and to develop a potential optimization of it by minimizing the error associated with the keratometric estimation of the corneal power and by developing a predictive formula for the effective lens position (ELP). MATERIALS AND METHODS: Clinical data from 25 eyes of 14 patients (age range, 52-77 years) and undergoing cataract surgery with implantation of the accommodating IOL Crystalens HD (Bausch and Lomb) were retrospectively reviewed. In all cases, the calculation of an adjusted IOL power (P(IOLadj)) based on Gaussian optics considering the residual refractive error was done using a variable keratometric index value (n(kadj)) for corneal power estimation with and without using an estimation algorithm for ELP obtained by multiple regression analysis (ELP(adj)). P(IOLadj) was compared to the real IOL power implanted (P(IOLReal), calculated with the SRK-T formula) and also to the values estimated by the Haigis, HofferQ, and Holladay I formulas. RESULTS: No statistically significant differences were found between P(IOLReal) and P(IOLadj) when ELP(adj) was used (P = 0.10), with a range of agreement between calculations of 1.23 D. In contrast, P(IOLReal) was significantly higher when compared to P(IOLadj) without using ELP(adj) and also compared to the values estimated by the other formulas. CONCLUSIONS: Predictable refractive outcomes can be obtained with the accommodating IOL Crystalens HD using a variable keratometric index for corneal power estimation and by estimating ELP with an algorithm dependent on anatomical factors and age. PMID- 26139809 TI - Bilateral optic disk metastasis from breast carcinoma. PMID- 26139808 TI - Choroidal thickness changes after dynamic exercise as measured by spectral-domain optical coherence tomography. AB - PURPOSE: To measure the choroidal thickness (CT) after dynamic exercise by using enhanced depth imaging optical coherence tomography (EDI-OCT). MATERIALS AND METHODS: A total of 19 healthy participants performed 10 min of low-impact, moderate-intensity exercise (i.e., riding a bicycle ergometer) and were examined with EDI-OCT. Each participant was scanned before exercise and afterward at 5 min and 15 min. CT measurement was taken at the fovea and 1000 MU away from the fovea in the nasal, temporal, superior, and inferior regions. Retinal thickness, intraocular pressure, ocular perfusion pressure (OPP), heart rate, and mean blood pressure (mBP) were also measured. RESULTS: A significant increase occurred in OPP and mBP at 5 min and 15 min following exercise (P ? 0.05). The mean subfoveal CT at baseline was 344.00 +/- 64.71 MUm compared to 370.63 +/- 66.87 MUm at 5 min and 345.31 +/- 63.58 MUm at 15 min after exercise. CT measurements at all locations significantly increased at 5 min following exercise compared to the baseline (P ? 0.001), while measurements at 15 min following exercise did not significant differ compared to the baseline (P ? 0.05). There was no significant difference in retinal thickness at any location before and at 5 min and 15 min following exercise (P ? 0.05). CONCLUSION: Findings revealed that dynamic exercise causes a significant increase in CT for at least 5 min following exercise. PMID- 26139810 TI - Real-time in vivo micromorphology and histopathology of choroidal osteoma using enhanced depth imaging. AB - Choroidal osteoma is a usually unilateral benign tumor of the choroid composed of mature bone. Optical coherence tomography (OCT) has been used to image osteoma for several years. With the advent of enhanced depth imaging (EDI) feature of spectral-domain OCT (SD-OCT), better visualization of the morphology of choroidal lesions has been possible. Herein we present a case of choroidal osteoma in a 45 year-old woman, wherein in vivo morphology of the choroidal osteoma had been visualized using EDI technique of SD-OCT before and after performing photodynamic therapy. EDI OCT has proven to be a valuable noninvasive imaging modality, almost comparable to histopathological examination, for diagnosing choroidal osteomas and for providing an insight into the in vivo micromorphological changes occurring during the course of the disease. PMID- 26139811 TI - Optical coherence tomography and autofluorescence findings in chronic phototoxic maculopathy secondary to snow-reflected solar radiation. AB - A professional mountain trekker presented with gradual, moderate visual decline in one eye. The subnormal vision could not be explained by the examination of anterior and posterior segment of either eye, which was unremarkable. Optical coherence tomography and autofluorescence imaging revealed subtle defects in the outer retina, which correlated with the extent of visual disturbance. A novel presentation of retinal phototoxicity due to indirect solar radiation reflected from snow in inadequately protected eyes of a chronically exposed subject is reported. PMID- 26139812 TI - Mucoepidermoid carcinoma of the conjunctiva with lung metastasis. AB - A 36-year-old lady presented with redness and decreased vision in right eye since 6 months. She was earlier diagnosed of cavitary lung lesion, presumed secondary to tuberculosis and treated with anti-tubercular treatment for 4 months. Examination of affected right eye revealed nil light perception, conjunctival congestion with an exuberant mass in the inferotemporal bulbar conjunctiva, proptosis, iris neovascularization, 360 degrees closed angles, intraocular pressure of 48 mm Hg, exudative retinal detachment, uveal mass and orbital extension. A diagnostic needle biopsy of uveal mass revealed malignant cells. Computed tomography-guided lung biopsy revealed squamous cell carcinoma (SCC), indicating metastatic spread from the orbit. She underwent lid-sparing exenteration of the right eye. Histopathological examination of the orbital tissue revealed mucoepidermoid carcinoma arising from the conjunctiva with extensive invasion into the orbital tissue, muscle fibers, sclera, choroid and optic nerve. Multiple tumor emboli were seen in the lumen of orbital blood vessels. In conclusion, mucoepidermoid carcinoma of the conjunctiva is a rare, aggressive variant of SCC. Early intervention is essential to prevent intraocular invasion and systemic metastasis. PMID- 26139813 TI - Evaluation of ExPress glaucoma filtration device in Indian patients with advanced glaucoma. AB - ExPress glaucoma filtration device (GFD) has recently become available in India as a surgical option for glaucoma patients. We retrospectively evaluated the outcome of ExPress GFD in 12 eyes with advanced glaucoma with intraocular pressures (IOPs) not controlled on maximal tolerable medical therapy. The mean preoperative IOP of 29.58 +/- 7.13 mmHg decreased to 17.0 +/- 2.67 and 17.40 +/- 0.89 mmHg at 6 and 12 months after surgery. Absolute success (IOP <= 18 mmHg, with no additional glaucoma medications) was achieved in eight cases (66.7%) and qualified success (IOP <= 18 mmHg, with additional glaucoma medications) in two cases (16.7%) at 1-year after surgery. Early intervention was needed in 4 patients; two underwent anterior chamber reformation while the other two required needling. Two patients required resurgery. There was no significant change in the best corrected visual acuity postoperatively (P = 0.37). ExPress GFD does not seem to offer a benefit over standard trabeculectomy in patients with advanced glaucomatous disease in terms of IOP control or complication rate. However, due to the small sample size with a heterogeneous mixture of primary and secondary glaucoma's, we await further studies with a larger sample size and long-term follow-up, to see how the device performs. PMID- 26139814 TI - Rhinosporidiosis of the tarsal conjunctiva. AB - Rhinosporidiosis is a rare infection caused by Rhinosporidium seeberi, an organism classified in its own class, mesomycetozoea. It commonly affects mucus membranes namely the nasal mucosa, pharynx and the conjunctiva. We present the case of an 8-year-old female who presented with a flat, red, vascular, fleshy, pedunculated mass arising from the tarsal conjunctiva of the right upper eyelid. The mass was completely excised. On histopathological examination, multiple sporangia were seen in various stages of degeneration, consistent with rhinosporidiosis. The diagnosis of rhinosporidiosis is based solely on its microscopic features, and the treatment is surgical excision. This condition is endemic in the temperate regions of the Indian subcontinent, but it has been known to occur even in the colder regions of North America and Eastern Europe. Although a rare clinical entity, the possibility of rhinosporidiosis must be borne in mind when evaluating any polypoidal conjunctival mass. PMID- 26139815 TI - Palmaris longus tendon assisted temporalis muscle transfer for lagophthalmos. PMID- 26139816 TI - Re: Long-term results after primary intraocular lens implantation in children operated less than 2 years of age for congenital cataract. PMID- 26139817 TI - Re: Scleral fixation of one piece intraocular lens by injector implantation. PMID- 26139818 TI - Sterile endophthalmitis following intravitreal triamcinolone acetonide in July 2010. PMID- 26139819 TI - Hypermetropia, accommodative and decompensated/partially accommodative esotropia and esotropic Duane's retraction syndrome in infants: Words impact understanding. PMID- 26139820 TI - Intravitreal ziv-aflibercept for recurrent macular edema secondary to central retinal venous occlusion. PMID- 26139821 TI - Malate as a key carbon source of leaf dark-respired CO2 across different environmental conditions in potato plants. AB - Dissimilation of carbon sources during plant respiration in support of metabolic processes results in the continuous release of CO2. The carbon isotopic composition of leaf dark-respired CO2 (i.e. delta (13) C R ) shows daily enrichments up to 14.80/00 under different environmental conditions. However, the reasons for this (13)C enrichment in leaf dark-respired CO2 are not fully understood, since daily changes in delta(13)C of putative leaf respiratory carbon sources (delta (13) C RS ) are not yet clear. Thus, we exposed potato plants (Solanum tuberosum) to different temperature and soil moisture treatments. We determined delta (13) C R with an in-tube incubation technique and delta (13) C RS with compound-specific isotope analysis during a daily cycle. The highest delta (13) C RS values were found in the organic acid malate under different environmental conditions, showing less negative values compared to delta (13) C R (up to 5.20/00) and compared to delta (13) C RS of soluble carbohydrates, citrate and starch (up to 8.80/00). Moreover, linear relationships between delta (13) C R and delta (13) C RS among different putative carbon sources were strongest for malate during daytime (r(2)=0.69, P<=0.001) and nighttime (r(2)=0.36, P<=0.001) under all environmental conditions. A multiple linear regression analysis revealed delta (13) C RS of malate as the most important carbon source influencing delta (13) C R . Thus, our results strongly indicate malate as a key carbon source of (13)C enriched dark-respired CO2 in potato plants, probably driven by an anapleurotic flux replenishing intermediates of the Krebs cycle. PMID- 26139822 TI - Salt-induced transcription factor MYB74 is regulated by the RNA-directed DNA methylation pathway in Arabidopsis. AB - Salt stress is one of the major abiotic stresses in agriculture worldwide that causes crop failure by interfering with the profile of gene expression and cell metabolism. Transcription factors and RNA-directed DNA methylation (RdDM) play an important role in the regulation of gene activation under abiotic stress in plants. This work characterized AtMYB74, a member of the R2R3-MYB gene family, which is transcriptionally regulated mainly by RdDM as a response in salt stress in Arabidopsis. Bisulphite sequencing indicated that 24-nt siRNAs target a region approximately 500bp upstream of the transcription initiation site of AtMYB74, which is heavily methylated. Levels of DNA methylation in this region were significantly reduced in wild type plants under salt stress, whereas no changes were found in RdDM mutants. Northern blot and quantitative real-time reverse transcription PCR analysis showed that the accumulation of 24-nt siRNAs was decreased in WT plants under salt stress. Further promoter deletion analysis revealed that the siRNA target region is essential for maintaining AtMYB74 expression patterns. In addition, transgenic plants overexpressing AtMYB74 displayed hypersensitivity to NaCl during seed germination. These results suggest that changes in the levels of the five 24-nt siRNAs regulate the AtMYB74 transcription factor via RdDM in response to salt stress. PMID- 26139823 TI - Non-specific lipid transfer proteins in plants: presenting new advances and an integrated functional analysis. AB - Plant non-specific lipid-transfer proteins (nsLTPs) are small, basic proteins present in abundance in higher plants. They are involved in key processes of plant cytology, such as the stablization of membranes, cell wall organization, and signal transduction. nsLTPs are also known to play important roles in resistance to biotic and abiotic stress, and in plant growth and development, such as sexual reproduction, seed development and germination. The structures of plant nsLTPs contain an eight-cysteine residue conserved motif, linked by four disulfide bonds, and an internal hydrophobic cavity, which comprises the lipid binding site. This structure endows stability and increases the ability to bind and/or carry hydrophobic molecules. There is growing interest in nsLTPs, due to their critical roles, resulting in the need for a comprehensive review of their form and function. Relevant topics include: nsLTP structure and biochemical features, their classification, identification, and characterization across species, sub-cellular localization, lipid binding and transfer ability, expression profiling, functionality, and evolution. We present advances, as well as limitations and trends, relating to the different topics of the nsLTP gene family. This review collates a large body of research pertaining to the role of nsLTPs across the plant kingdom, which has been integrated as an in depth functional analysis of this group of proteins as a whole, and their activities across multiple biochemical pathways, based on a large number of reports. This review will enhance our understanding of nsLTP activity in planta, prompting further work and insights into the roles of this multifaceted protein family in plants. PMID- 26139824 TI - Endoplasmic reticulum localization and activity of maize auxin biosynthetic enzymes. AB - Auxin is a major growth hormone in plants and the first plant hormone to be discovered and studied. Active research over >60 years has shed light on many of the molecular mechanisms of its action including transport, perception, signal transduction, and a variety of biosynthetic pathways in various species, tissues, and developmental stages. The complexity and redundancy of the auxin biosynthetic network and enzymes involved raises the question of how such a system, producing such a potent agent as auxin, can be appropriately controlled at all. Here it is shown that maize auxin biosynthesis takes place in microsomal as well as cytosolic cellular fractions from maize seedlings. Most interestingly, a set of enzymes shown to be involved in auxin biosynthesis via their activity and/or mutant phenotypes and catalysing adjacent steps in YUCCA-dependent biosynthesis are localized to the endoplasmic reticulum (ER). Positioning of auxin biosynthetic enzymes at the ER could be necessary to bring auxin biosynthesis in closer proximity to ER-localized factors for transport, conjugation, and signalling, and allow for an additional level of regulation by subcellular compartmentation of auxin action. Furthermore, it might provide a link to ethylene action and be a factor in hormonal cross-talk as all five ethylene receptors are ER localized. PMID- 26139825 TI - beta-amylase1 mutant Arabidopsis plants show improved drought tolerance due to reduced starch breakdown in guard cells. AB - In plants, drought stress is a major growth limiting factor causing cell water loss through open stomata. In this study, guard cell-specific transcripts from drought-stressed Arabidopsis plants were analysed and a down-regulation of beta amylase 1 (BAM1) was found. In previous studies, BAM1 was shown to be involved in stomatal starch degradation under ambient conditions. Impaired starch breakdown of bam1 mutant plants was accompanied by decreased stomatal opening. Here, it is shown that drought tolerance of bam1 mutant plants is improved as compared with wild-type controls. Microarray analysis of stomata-specific transcripts from bam1 mutant plants revealed a significant down-regulation of genes encoding aquaporins, auxin- and ethylene-responsive factors, and cell-wall modifying enzymes. This expression pattern suggests that reduced water uptake and limited cell wall extension are associated with the closed state of stomata of bam1 mutant plants. Together these data suggest that regulation of stomata-specific starch turnover is important for adapting stomata opening to environmental needs and its breeding manipulation may result in drought tolerant crop plants. PMID- 26139826 TI - Effect of sulphur deprivation on osmotic potential components and nitrogen metabolism in oilseed rape leaves: identification of a new early indicator. AB - Identification of early sulphur (S) deficiency indicators is important for species such as Brassica napus, an S-demanding crop in which yield and the nutritional quality of seeds are negatively affected by S deficiency. Because S is mostly stored as SO4 (2-) in leaf cell vacuoles and can be mobilized during S deficiency, this study investigated the impact of S deprivation on leaf osmotic potential in order to identify compensation processes. Plants were exposed for 28 days to S or to chlorine deprivation in order to differentiate osmotic and metabolic responses. While chlorine deprivation had no significant effects on growth, osmotic potential and nitrogen metabolism, Brassica napus revealed two response periods to S deprivation. The first one occurred during the first 13 days during which plant growth was maintained as a result of vacuolar SO4 (2-) mobilization. In the meantime, leaf osmotic potential of S-deprived plants remained similar to control plants despite a reduction in the SO4 (2-) osmotic contribution, which was fully compensated by an increase in NO3 (-), PO4 (3-) and Cl(-) accumulation. The second response occurred after 13 days of S deprivation with a significant reduction in growth, leaf osmotic potential, NO3 (-) uptake and NO3 (-) reductase activity, whereas amino acids and NO3 (-) were accumulated. This kinetic analysis of S deprivation suggested that a ([Cl(-)]+[NO3 (-)]+[PO4 (3-)]):[SO4 (2-)] ratio could provide a relevant indicator of S deficiency, modified nearly as early as the over-expression of genes encoding SO4 (2-) tonoplastic or plasmalemmal transporters, with the added advantage that it can be easily quantified under field conditions. PMID- 26139827 TI - FLOWERING LOCUS T has higher protein mobility than TWIN SISTER OF FT. AB - In plants, successful reproduction requires the proper timing of flowering under changing environmental conditions. Arabidopsis FLOWERING LOCUS T (FT), which encodes a proposed phloem-mobile florigen, has a close homologue, TWIN SISTER OF FT (TSF). During the vegetative phase, TSF shows high levels of expression in the hypocotyl before FT induction, but the tsf mutation does not have an apparent flowering-time phenotype on its own under long-day conditions. This study compared the protein mobility of FT and TSF. With TSF-overexpressing plants as the rootstock, the flowering time of ft tsf scion plants was only slightly accelerated. Previous work has shown that FT is graft-transmissible; by contrast, this study did not detect movement of TSF from the roots into the shoot of the scion plants. This study used plants overexpressing FT/TSF chimeric proteins to map a region responsible for FT movement. A chimeric TSF with region II of FT (L28 to G98) expressed in the rootstock caused early flowering in ft tsf scion plants; movement of the chimeric protein from the rootstocks into the shoot apical region of the ft tsf scion plants was also detected. Misexpression of TSF in the leaf under the control of the FT promoter or grafting of 35S::TSF cotyledons accelerated flowering of ft-10 plants. FT was more stable than TSF. Taking these results together, we propose that protein mobility of FT is higher than that of TSF, possibly due to a protein domain that confers mobility and/or protein stability. PMID- 26139828 TI - Development and Validation of MMPI-2-RF Scales for Indexing Triarchic Psychopathy Constructs. AB - The triarchic model characterizes psychopathy in terms of three distinct dispositional constructs of boldness, meanness, and disinhibition. The model can be operationalized through scales designed specifically to index these domains or by using items from other inventories that provide coverage of related constructs. The present study sought to develop and validate scales for assessing the triarchic model domains using items from the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). A consensus rating approach was used to identify items relevant to each triarchic domain, and following psychometric refinement, the resulting MMPI-2-RF-based triarchic scales were evaluated for convergent and discriminant validity in relation to multiple psychopathy-relevant criterion variables in offender and nonoffender samples. Expected convergent and discriminant associations were evident very clearly for the Boldness and Disinhibition scales and somewhat less clearly for the Meanness scale. Moreover, hierarchical regression analyses indicated that all MMPI-2-RF triarchic scales incremented standard MMPI-2-RF scale scores in predicting extant triarchic model scale scores. The widespread use of MMPI-2-RF in clinical and forensic settings provides avenues for both clinical and research applications in contexts where traditional psychopathy measures are less likely to be administered. PMID- 26139829 TI - Measurement Invariance and the Five-Factor Model of Personality: Asian International and Euro American Cultural Groups. AB - This study examined measurement invariance of the NEO Five-Factor Inventory (NEO FFI), assessing the five-factor model (FFM) of personality among Euro American (N = 290) and Asian international (N = 301) students (47.8% women, Mage = 19.69 years). The full 60-item NEO-FFI data fit the expected five-factor structure for both groups using exploratory structural equation modeling, and achieved configural invariance. Only 37 items significantly loaded onto the FFM-theorized factors for both groups and demonstrated metric invariance. Threshold invariance was not supported with this reduced item set. Groups differed the most in the item-factor relationships for Extraversion and Agreeableness, as well as in response styles. Asian internationals were more likely to use midpoint responses than Euro Americans. While the FFM can characterize broad nomothetic patterns of personality traits, metric invariance with only the subset of NEO-FFI items identified limits direct group comparisons of correlation coefficients among personality domains and with other constructs, and of mean differences on personality domains. PMID- 26139830 TI - Item Response Theory Analysis of ADHD Symptoms in Children With and Without ADHD. AB - Item response theory (IRT) was separately applied to parent- and teacher-rated symptoms of attention-deficit/hyperactivity disorder (ADHD) from a pooled sample of 526 six- to twelve-year-old children with and without ADHD. The dimensional structure ADHD was first examined using confirmatory factor analyses, including the bifactor model. A general ADHD factor and two group factors, representing inattentive and hyperactive/impulsive dimensions, optimally fit the data. Using the graded response model, we estimated discrimination and location parameters and information functions for all 18 symptoms of ADHD. Parent- and teacher-rated symptoms demonstrated adequate discrimination and location values, although these estimates varied substantially. For parent ratings, the test information curve peaked between -2 and +2 SD, suggesting that ADHD symptoms exhibited excellent overall reliability at measuring children in the low to moderate range of the general ADHD factor, but not in the extreme ranges. Similar results emerged for teacher ratings, in which the peak range of measurement precision was from -1.40 to 1.90 SD Several symptoms were comparatively more informative than others; for example, is often easily distracted ("Distracted") was the most informative parent- and teacher-rated symptom across the latent trait continuum. Clinical implications for the assessment of ADHD as well as relevant considerations for future revisions to diagnostic criteria are discussed. PMID- 26139831 TI - Evidence of Statistical Inconsistency of Phylogenetic Methods in the Presence of Multiple Sequence Alignment Uncertainty. AB - Evolutionary studies usually use a two-step process to investigate sequence data. Step one estimates a multiple sequence alignment (MSA) and step two applies phylogenetic methods to ask evolutionary questions of that MSA. Modern phylogenetic methods infer evolutionary parameters using maximum likelihood or Bayesian inference, mediated by a probabilistic substitution model that describes sequence change over a tree. The statistical properties of these methods mean that more data directly translates to an increased confidence in downstream results, providing the substitution model is adequate and the MSA is correct. Many studies have investigated the robustness of phylogenetic methods in the presence of substitution model misspecification, but few have examined the statistical properties of those methods when the MSA is unknown. This simulation study examines the statistical properties of the complete two-step process when inferring sequence divergence and the phylogenetic tree topology. Both nucleotide and amino acid analyses are negatively affected by the alignment step, both through inaccurate guide tree estimates and through overfitting to that guide tree. For many alignment tools these effects become more pronounced when additional sequences are added to the analysis. Nucleotide sequences are particularly susceptible, with MSA errors leading to statistical support for long branch attraction artifacts, which are usually associated with gross substitution model misspecification. Amino acid MSAs are more robust, but do tend to arbitrarily resolve multifurcations in favor of the guide tree. No inference strategies produce consistently accurate estimates of divergence between sequences, although amino acid MSAs are again more accurate than their nucleotide counterparts. We conclude with some practical suggestions about how to limit the effect of MSA uncertainty on evolutionary inference. PMID- 26139834 TI - Using Conditional Percentages During Free-Operant Stimulus Preference Assessments to Predict the Effects of Preferred Items on Stereotypy: Preliminary Findings. AB - To date, researchers have not identified an efficient methodology for selecting items that will compete with automatically reinforced behavior. In the present study, we identified high preference, high stereotypy (HP-HS), high preference, low stereotypy (HP-LS), low preference, high stereotypy (LP-HS), and low preference, low stereotypy (LP-LS) items based on response allocation to items and engagement in stereotypy during one to three, 30-min free-operant competing stimulus assessments (CSAs). The results showed that access to HP-LS items decreased stereotypy for all four participants; however, the results for other items were only predictive for one participant. Reanalysis of the CSA results revealed that the HP-LS item was typically identified by (a) the combined results of the first 10 min of the three 30-min assessments or (b) the results of one 30 min assessment. The clinical implications for the use of this method, as well as future directions for research, are briefly discussed. PMID- 26139832 TI - Dynamic Evolution of the Chloroplast Genome in the Green Algal Classes Pedinophyceae and Trebouxiophyceae. AB - Previous studies of trebouxiophycean chloroplast genomes revealed little information regarding the evolutionary dynamics of this genome because taxon sampling was too sparse and the relationships between the sampled taxa were unknown. We recently sequenced the chloroplast genomes of 27 trebouxiophycean and 2 pedinophycean green algae to resolve the relationships among the main lineages recognized for the Trebouxiophyceae. These taxa and the previously sampled members of the Pedinophyceae and Trebouxiophyceae are included in the comparative chloroplast genome analysis we report here. The 38 genomes examined display considerable variability at all levels, except gene content. Our results highlight the high propensity of the rDNA-containing large inverted repeat (IR) to vary in size, gene content and gene order as well as the repeated losses it experienced during trebouxiophycean evolution. Of the seven predicted IR losses, one event demarcates a superclade of 11 taxa representing 5 late-diverging lineages. IR expansions/contractions account not only for changes in gene content in this region but also for changes in gene order and gene duplications. Inversions also led to gene rearrangements within the IR, including the reversal or disruption of the rDNA operon in some lineages. Most of the 20 IR-less genomes are more rearranged compared with their IR-containing homologs and tend to show an accelerated rate of sequence evolution. In the IR-less superclade, several ancestral operons were disrupted, a few genes were fragmented, and a subgroup of taxa features a G+C-biased nucleotide composition. Our analyses also unveiled putative cases of gene acquisitions through horizontal transfer. PMID- 26139835 TI - Guest Editor's Introduction. PMID- 26139833 TI - Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses. AB - Viruses rely completely on the hosts' machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response. PMID- 26139836 TI - Association of Monocyte-to-HDL Cholesterol Ratio with Slow Coronary Flow is Linked to Systemic Inflammation. AB - BACKGROUND: Previous studies proposed that both inflammation, oxidative stress, and impaired endothelial dysfunction have a significant role in occurrence of slow coronary flow (SCF). monocyte-to-high density lipoprotein cholesterol ratio (MHR) is a recently emerged indicator of inflammation and oxidative stress, which have been studied only in patients with chronic kidney disease. HYPOTHESIS: We aimed to assess the relationship between MHR and SCF. METHODS: Patients who had angiographically normal coronary arteries were enrolled in this retrospective study (n = 253 as SCF group and n = 176 as control group). Patients who had corrected thrombolysis in myocardial infarction frame counts (cTFCs) above the normal cutoffs were defined as with SCF. RESULTS: The MHR and high-sensitivity C reactive protein (hsCRP) were significantly higher in the SCF group. In correlation analysis, MHR has a significantly positive correlation with cTFC and serum hsCRP levels (P < .001). In multivariate logistic regression analysis, MHR was found as independently associated with the presence of SCF (odds ratio: 1.24, P < .001). CONCLUSION: Higher MHR which indicates an enhanced inflammation and oxidative stress was significantly and independently associated with the presence of SCF. Besides, MHR was positively correlated with serum hsCRP level as a conventional marker for systemic inflammation. PMID- 26139837 TI - Hypofibrinogenemia and the alpha-Fibrinogen Thr312Ala Polymorphism may be Risk Factors for Early Pregnancy Loss. AB - We analyzed a cohort of 36 females with pregnancy loss. In addition to 11 patients with antiphospholipid antibody syndrome and 2 patients with congenital antithrombin (AT) or protein C deficiency, we identified 5 patients with low fibrinogen levels (median 110 mg/dL) prior to 10 weeks of gestation. Four of these 5 patients underwent a fibrinogen gene analysis, and all 4 were found to be heterozygotes for the alpha-fibrinogen (FGA) Thr321Ala polymorphism. One female without hypofibrinogenemia with a history of 8 pregnancy losses was found to be homozygous for the same polymorphism, and she also showed hypercoagulability without thrombosis. In conclusion, there was a relatively high frequency of pregnancy loss in the setting of hypofibrinogenemia and/or the FGA Thr312Ala polymorphism, and this may be an important risk factor for pregnancy loss and a hypercoagulable state in later pregnancy. PMID- 26139838 TI - Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs. AB - Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development. PMID- 26139839 TI - Multiple-Line Inference of Selection on Quantitative Traits. AB - Trait differences between species may be attributable to natural selection. However, quantifying the strength of evidence for selection acting on a particular trait is a difficult task. Here we develop a population genetics test for selection acting on a quantitative trait that is based on multiple-line crosses. We show that using multiple lines increases both the power and the scope of selection inferences. First, a test based on three or more lines detects selection with strongly increased statistical significance, and we show explicitly how the sensitivity of the test depends on the number of lines. Second, a multiple-line test can distinguish between different lineage-specific selection scenarios. Our analytical results are complemented by extensive numerical simulations. We then apply the multiple-line test to QTL data on floral character traits in plant species of the Mimulus genus and on photoperiodic traits in different maize strains, where we find a signature of lineage-specific selection not seen in two-line tests. PMID- 26139841 TI - Know Your Value: Negotiation Skill Development for Junior Investigators in the Academic Environment--A Report from the American Society of Preventive Oncology's Junior Members Interest Group. PMID- 26139842 TI - Dissociation of Neural Networks for Predisposition and for Training-Related Plasticity in Auditory-Motor Learning. AB - Skill learning results in changes to brain function, but at the same time individuals strongly differ in their abilities to learn specific skills. Using a 6-week piano-training protocol and pre- and post-fMRI of melody perception and imagery in adults, we dissociate learning-related patterns of neural activity from pre-training activity that predicts learning rates. Fronto-parietal and cerebellar areas related to storage of newly learned auditory-motor associations increased their response following training; in contrast, pre-training activity in areas related to stimulus encoding and motor control, including right auditory cortex, hippocampus, and caudate nuclei, was predictive of subsequent learning rate. We discuss the implications of these results for models of perceptual and of motor learning. These findings highlight the importance of considering individual predisposition in plasticity research and applications. PMID- 26139843 TI - Whole Organism Genome Editing: Targeted Large DNA Insertion via ObLiGaRe Nonhomologous End-Joining in Vivo Capture. AB - Targeted gene insertion is a goal of genome editing and has been performed in cultured cells but only in a handful of whole organisms. The existing method to integrate foreign DNA using the homologous recombination pathway is inherently low efficiency, and many systems are refractory to this method. Several additional manipulations have been developed to gain greater efficiency by suppressing the competing dominant repair pathway of nonhomologous end-joining. However, this can be laborious and in practice limits the range of hosts where the method is applicable. Here, we use the preferred pathway of nonhomologous end joining (used previously to create indels for gene inactivation) for precise integration of large DNA into the specified genomic target site of an intact animal. Our method uses site-specific cleavage, end-capture of cohesive ends, and obligate ligation-gated recombination. This approach is straight-forward and yields high efficiency without additional gene manipulations; therefore it is easily applicable to a much broader range of organisms. We demonstrate its application to the fungus fly Sciara coprophila where a transformation system has not existed before. We integrated a 6.5 kb transgene precisely at the desired genomic target site of Sciara using this method. This provides the foundation for future experiments to explore the unique genetic features of this organism. Similarly, the method described here will allow insertion of large pieces of DNA into a diverse group of organisms for studies of their genetic attributes. PMID- 26139844 TI - Exome Sequencing: Current and Future Perspectives. PMID- 26139846 TI - Antifungal Prophylaxis With Posaconazole Is Effective in Preventing Invasive Fungal Infections in Acute Myeloid Leukemia Patients During Induction and Salvage Chemotherapy. PMID- 26139845 TI - Whole-Exome Sequencing and Targeted Copy Number Analysis in Primary Ciliary Dyskinesia. AB - Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder resulting from loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus, and infertility. Clinical features may be subtle and highly variable, making the diagnosis of PCD challenging. The diagnosis can be confirmed with ciliary ultrastructure analysis and/or molecular genetic testing of 32 PCD-associated genes. However, because of this genetic heterogeneity, comprehensive molecular genetic testing is not considered the standard of care, and the most efficient molecular approach has yet to be elucidated. Here, we propose a cost-effective and time-efficient molecular genetic algorithm to solve cases of PCD. We conducted targeted copy number variation (CNV) analysis and/or whole-exome sequencing on 20 families (22 patients) from a subset of 45 families (52 patients) with a clinical diagnosis of PCD who did not have a molecular genetic diagnosis after Sanger sequencing of 12 PCD-associated genes. This combined molecular genetic approach led to the identification of 4 of 20 (20%) families with clinically significant CNVs and 7 of 20 (35%) families with biallelic pathogenic mutations in recently identified PCD genes, resulting in an increased molecular genetic diagnostic rate of 55% (11/20). In patients with a clinical diagnosis of PCD, whole-exome sequencing followed by targeted CNV analysis results in an overall molecular genetic yield of 76% (34/45). PMID- 26139847 TI - Reply to Wong et al. PMID- 26139849 TI - Treatment-resistant major depressive disorder and assisted dying: response to comments. PMID- 26139848 TI - Label-free Quantitative Proteomics of Mouse Cerebrospinal Fluid Detects beta-Site APP Cleaving Enzyme (BACE1) Protease Substrates In Vivo. AB - Analysis of murine cerebrospinal fluid (CSF) by quantitative mass spectrometry is challenging because of low CSF volume, low total protein concentration, and the presence of highly abundant proteins such as albumin. We demonstrate that the CSF proteome of individual mice can be analyzed in a quantitative manner to a depth of several hundred proteins in a robust and simple workflow consisting of single ultra HPLC runs on a benchtop mass spectrometer. The workflow is validated by a comparative analysis of BACE1-/- and wild-type mice using label-free quantification. The protease BACE1 cleaves the amyloid precursor protein (APP) as well as several other substrates and is a major drug target in Alzheimer's disease. We identified a total of 715 proteins with at least 2 unique peptides and quantified 522 of those proteins in CSF from BACE1-/- and wild-type mice. Several proteins, including the known BACE1 substrates APP, APLP1, CHL1 and contactin-2 showed lower abundance in the CSF of BACE1-/- mice, demonstrating that BACE1 substrate identification is possible from CSF. Additionally, ectonucleotide pyrophosphatase 5 was identified as a novel BACE1 substrate and validated in cells using immunoblots and by an in vitro BACE1 protease assay. Likewise, receptor-type tyrosine-protein phosphatase N2 and plexin domain containing 2 were confirmed as BACE1 substrates by in vitro assays. Taken together, our study shows the deepest characterization of the mouse CSF proteome to date and the first quantitative analysis of the CSF proteome of individual mice. The BACE1 substrates identified in CSF may serve as biomarkers to monitor BACE1 activity in Alzheimer patients treated with BACE inhibitors. PMID- 26139850 TI - On the univocity of rationality: a response to Nigel Biggar's 'Why religion deserves a place in secular medicine'. AB - Nigel Biggar (2015) argues that religion deserves a place in secular medicine. Biggar suggests we abandon the standard rationalistic conception of the secular realm and see it rather as "a forum for the negotiation of rival reasonings". Religious reasoning is one among a number of ways of thinking that must vie for acceptance. Medical ethics, says Biggar, is characterised by "spiritual and moral mixture and ambiguity". We acknowledge this uncertainty by recognising rival viewpoints and agreeing to provisional compromises.In this response, I object to Biggar's characterisation of medical ethics as "morally ambiguous" and "provisional". I argue that Biggar has failed to provide adequate support for his conception of ethics as a "forum for negotiation and compromise". I criticise Biggar's attempt to 'pluralise' rationality, and assert that if religion is to play a role in secular medicine, it must be ready to defend itself against a universal standard of reason. In the second section of my response, I argue that 'theistic natural law' gives us the resources to defend using reason alone ostensibly faith-based positions in healthcare ethics. In doing so, we retain a univocal conception of rationality, while at the same time leaving space for 'theism' in healthcare ethics. PMID- 26139851 TI - Public participation in genetic databases: crossing the boundaries between biobanks and forensic DNA databases through the principle of solidarity. AB - The ethical aspects of biobanks and forensic DNA databases are often treated as separate issues. As a reflection of this, public participation, or the involvement of citizens in genetic databases, has been approached differently in the fields of forensics and medicine. This paper aims to cross the boundaries between medicine and forensics by exploring the flows between the ethical issues presented in the two domains and the subsequent conceptualisation of public trust and legitimisation. We propose to introduce the concept of 'solidarity', traditionally applied only to medical and research biobanks, into a consideration of public engagement in medicine and forensics. Inclusion of a solidarity-based framework, in both medical biobanks and forensic DNA databases, raises new questions that should be included in the ethical debate, in relation to both health services/medical research and activities associated with the criminal justice system. PMID- 26139853 TI - A platform for reverse genetics in endothelial cells. PMID- 26139854 TI - MMP17/MT4-MMP and thoracic aortic aneurysms: OPNing new potential for effective treatment. PMID- 26139855 TI - Thrombospondin-1: an extracellular message delivered by macrophages that promotes aortic aneurysms. PMID- 26139857 TI - Novel role of bone marrow stem cells in systemic disease. PMID- 26139856 TI - Sweet dicer: impairment of micro-RNA processing by diabetes. PMID- 26139858 TI - Lncing epigenetic control of transcription to cardiovascular development and disease. AB - Transcriptional and epigenetic regulation is critical for proper heart development, cardiac homeostasis, and pathogenesis. Long noncoding RNAs have emerged as key components of the transcriptional regulatory pathways that govern cardiac development as well as stress response, signaling, and remodeling in cardiac pathologies. Within the past few years, studies have identified many long noncoding RNAs in the context of cardiovascular biology and have begun to reveal the key functions of these transcripts. In this review, we discuss the growing roles of long noncoding RNAs in different aspects of cardiovascular development as well as pathological responses during injury or disease. In addition, we discuss diverse mechanisms by which long noncoding RNAs orchestrate cardiac transcriptional programs. Finally, we explore the exciting potential of this novel class of transcripts as biomarkers and novel therapeutic targets for cardiovascular diseases. PMID- 26139860 TI - Correction. PMID- 26139861 TI - Infusing Neuroscience into Teacher Professional Development. AB - Bruer (1997) advocated connecting neuroscience and education indirectly through the intermediate discipline of psychology. We argue for a parallel route: the neurobiology of learning, and in particular the core concept of plasticity, have the potential to directly transform teacher preparation and professional development, and ultimately to affect how students think about their own learning. We present a case study of how the core concepts of neuroscience can be brought to in-service teachers - the BrainU workshops. We then discuss how neuroscience can be meaningfully integrated into pre-service teacher preparation, focusing on institutional and cultural barriers. PMID- 26139859 TI - Exercise and the cardiovascular system: clinical science and cardiovascular outcomes. AB - Substantial evidence has established the value of high levels of physical activity, exercise training (ET), and overall cardiorespiratory fitness in the prevention and treatment of cardiovascular diseases. This article reviews some basics of exercise physiology and the acute and chronic responses of ET, as well as the effect of physical activity and cardiorespiratory fitness on cardiovascular diseases. This review also surveys data from epidemiological and ET studies in the primary and secondary prevention of cardiovascular diseases, particularly coronary heart disease and heart failure. These data strongly support the routine prescription of ET to all patients and referrals for patients with cardiovascular diseases, especially coronary heart disease and heart failure, to specific cardiac rehabilitation and ET programs. PMID- 26139862 TI - Crystallization modifiers in lipid systems. AB - Crystallization of fats is a determinant physical event affecting the structure and properties of fat-based products. The stability of these processed foods is regulated by changes in the physical state of fats and alterations in their crystallization behavior. Problems like polymorphic transitions, oil migration, fat bloom development, slow crystallization and formation of crystalline aggregates stand out. The change of the crystallization behavior of lipid systems has been a strategic issue for the processing of foods, aiming at taylor made products, reducing costs, improving quality, and increasing the applicability and stability of different industrial fats. In this connection, advances in understanding the complex mechanisms that govern fat crystallization led to the development of strategies in order to modulate the conventional processes of fat structuration, based on the use of crystallization modifiers. Different components have been evaluated, such as specific triacyglycerols, partial glycerides (monoacylglycerols and diacylglycerols), free fatty acids, phospholipids and emulsifiers. The knowledge and expertise on the influence of these specific additives or minor lipids on the crystallization behavior of fat systems represents a focus of current interest for the industrial processing of oils and fats. This article presents a comprehensive review on the use of crystallization modifiers in lipid systems, especially for palm oil, cocoa butter and general purpose fats, highlighting: i) the removal, addition or fractionation of minor lipids in fat bases; ii) the use of nucleating agents to modify the crystallization process; iii) control of crystallization in lipid bases by using emulsifiers. The addition of these components into lipid systems is discussed in relation to the phenomena of nucleation, crystal growth, morphology, thermal behavior and polymorphism, with the intention of providing the reader with a complete panorama of the associated mechanisms with crystallization of fats and oils. PMID- 26139863 TI - Intelligent packaging in meat industry: An overview of existing solutions. AB - Traditional packaging systems are refused since these systems do not provide any information about the quality of food products to the consumers and manufacturers at any stage of supply chain. The essence of a new technology to monitor the food spoilage from farm to fork is emerged to reduce hazards such as food borne diseases. Moreover, the food quality monitoring systems clarify the main factors in food wastage during supply chain. Intelligent packaging is employed to provide information about the history of food handling and storage to enhance food products quality and meet consumer satisfactions. Meat is one of the most perishable foods which causes sever illnesses in the case of spoilage. Variety of indicators and sensors have been proposed to warn about meat spoilage in meat industry. In this paper an overview of proposed approaches as well as commercial technologies to monitor the quality of meat during storage and transportation is presented. Furthermore, the existing technologies are compared in the sense of advantages and disadvantages in meat packaging applications. PMID- 26139864 TI - Plant based butters. AB - During the last few years the popularity for the plant based butters (nut and seed butters) has increased considerably. Earlier peanut butter was the only alternative to the dairy butter, but over the years development in the technologies and also the consumer awareness about the plant based butters, has led the development of myriad varieties of butters with different nuts and seeds, which are very good source of protein, fiber, essential fatty acids and other nutrients. These days' different varieties of plant based butters are available in the market viz., peanut butter, soy butter, almond butter, pistachio butter, cashew butter and sesame butter etc. The form of butter is one of the healthy way of integrating nuts and seeds in to our regular diet. Nut and seed butters are generally prepared by roasting, grinding and refrigerated to consume it when it is still fresh. During this process it is imperative to retain the nutritional properties of these nuts and seeds in order to reap the benefits of the fresh nuts and seeds in the form of butter as well. Proper care is needed to minimize the conversion of healthful components in to unhealthy components during processing and further storage. Roasting temperature, temperatures during grinding and storage are the vital factors to be considered in order to have healthy and nutritious plant based butters. In this article, different plant based butters and their processing methods have been described. PMID- 26139865 TI - Chenopodium album Linn: review of nutritive value and biological properties. AB - Green leafy vegetables have generated interest worldwide as they exhibit multiple benefits for health of human beings. Vegetables can form the cheapest and most readily available sources of important vitamins, minerals, fibres and essential amino acids particularly. In most of the developing countries where the daily diet is dominated by starchy staple foods, vegetables can form the cheapest and most readily available sources of important vitamins, minerals, fibres and essential amino acids. Across the globe there are several local and wild vegetables which are under-exploited because of inadequate scientific information on knowledge of their nutritional potentials. A resurgence of interest has developed in wild vegetables for their possible medicinal values in diets. C. album is under exploited vegetable which has high functional potential apart from basic nutritional benefits. The plant is used in diet not only to provide minerals, fibre, vitamins and essential fatty acids but also enhance sensory and functional value of the food. The plant has been traditionally used as a bloodpurifier, diuretic, sedative, hepatoprotective, antiscorbutic laxative and as an anthelmentic against round and hookworms. Pharmacological studies have revealed that the plant possesses anthelmentic, sperm immobilizing and contraceptive properties. It is also claimed to be antipruritic and antinociceptive in action. Therefore C. album holds a great potential for in depth biological evaluation. No significant work has ever been carried out for processing parameters for this potentially useful plant. Significance and future scope of C. album for public and dietary awareness of its nutritional status has been discussed in this review. PMID- 26139866 TI - Antioxidant potential and quality characteristics of vegetable-enriched corn based extruded snacks. AB - Phenolic content, antioxidant activity and sensory characteristics of vegetable enriched extrudates were investigated as a result of extrusion conditions, including extrusion temperature (140-180 degrees C), screw rotation speed (150 250 rpm) and feed moisture content (14-19 % w.b.). Broccoli flour and olive paste was used in mixtures with corn flour at a ratio of 4 to 10 % (broccoli/corn) and 4 to 8 % (olive paste/corn). A simple power model was developed for the prediction of phenolic content and antioxidant activity of extrudates by extrusion conditions and feed composition. Phenolic content and antioxidant activity of broccoli enriched extrudates increased with extrusion temperature and broccoli addition and decreased with feed moisture content. The antioxidant activity of olive paste extrudates increased with material ratio and decreased with feed moisture content and screw rotation. Sensory porosity, homogenous structure, crispness, cohesiveness and melting decreased with feed moisture content, while the latter increased the mealy flavor and hardness of extrudates. Acceptable snacks containing broccoli flour or olive paste can be produced by selecting the appropriate process conditions. PMID- 26139868 TI - Development of technology for manufacture of ragi ice cream. AB - Ragi (Finger millet) improves the nutritional value of ice cream by enhancing the iron and fibre content. Caramel flavoured medium fat ice cream (6 % fat) was prepared by addition of gelatinized malted ragi flour roasted in butter (MRB) @ 8 %, 9 % and 10 % by weight of mix and compared with control (C) i.e. vanilla ice cream containing 10 % fat. The overall acceptability score of product prepared using 9 % MRB was statistically (P > 0.05) at par with the C, hence, it was selected. In the next part of the study, ragi ice cream was prepared using 4 different flavours viz. vanilla, mango, chocolate and caramel. Chocolate flavoured ragi ice cream was adjudged as best, followed by mango, caramel and vanilla ice cream. The iron and fibre content of chocolate flavoured ragi ice cream was found to be 12.8 ppm and 1.36 % respectively. vs. 1.5 ppm and 0.18 % respectively in control (C). Heat shock treatment as well as storage up to 30 days had no adverse effect on the sensory quality of the chocolate flavored ragi ice cream. Incorporation of finger millet in ice cream resulted in reduction in the amount of stabilizer used and effectively functioned as fat replacer in ice cream. PMID- 26139867 TI - Simultaneous analysis of herbicides pendimethalin, oxyfluorfen, imazethapyr and quizalofop-p-ethyl by LC-MS/MS and safety evaluation of their harvest time residues in peanut (Arachis hypogaea L.). AB - This paper reports a simple and rapid method for simultaneous determination of the residues of selected herbicides viz. pendimethalin, oxyfluorfen, imazethapyr and quizalofop-p-ethyl in peanut by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A modified approach of the QuEChERS methodology was used to extract the herbicides from the peanut kernel without any clean-up. The method showed excellent linearity (r(2) > 0.99) with no significant matrix effect. Accuracy of the method in terms of average recoveries of all the four herbicides ranged between 69.4 -94.4 % at spiking levels of 0.05, 0.10 and 0.25 mg kg(-1) with intra-day and inter-day precision RSD (%) between 2.6-16.6 and 8.0-11.3, respectively. Limit of quantification (LOQs) was 5.0 MUg kg(-1) for pendimethalin, imazethapyr and quizalofop-p-ethyl and 10.0 MUg kg(-1) for oxyfluorfen. The expanded uncertainties were <11 % for determination of these herbicides in peanut. The proposed method was successfully applied for analysis of these herbicide residues in peanut samples harvested from the experimental field and the residues were below the detection level. PMID- 26139869 TI - Microencapsulation of Lactobacillus plantarum MTCC 5422 in fructooligosaccharide and whey protein wall systems and its impact on noodle quality. AB - Noodles are staple cereal food in many countries; however addition of encapsulated probiotics into noodle formulation, its effect on noodle quality and cell viability has not yet been reported. The aim of this study was to prepare microencapsulated Lactobacillus plantarum (MTCC 5422) by freeze drying with wall material combinations such as fructooligosaccharide (FOS), FOS + whey protein isolate (WPI), and FOS + denatured whey protein isolate (DWPI) to evaluate best wall system. Results showed that FOS + DWPI wall system provided better protection to cells after drying, during storage (60 days, 4 degrees C) and in simulated acidic and bile conditions. Further, FOS + DWPI encapsulates were incorporated into noodle formulation and evaluated the noodle quality and probiotic cell viability of cooked noodle obtained from two different production methods: (i) fresh and (ii) dried (room temperature dried - RTD, 28 degrees C and high temperature dried - HTD, 55 degrees C). The quality characteristics (cooking time, solid loss, texture, colour and sensory profiles) of FOS + DWPI encapsulates incorporated cooked noodles (both fresh and dried) were found to be acceptable. On evaluation of encapsulated probiotic bacteriaL. plantarum cell viability, 93.63 % and 62.42 % cell survival was obtained in fresh noodles before and after cooking respectively. However, 80.29 % (RTD) and 64.74 % (HTD) of encapsulated cells were viable in dried noodles, after cooking there was complete survival loss. This study suggested that fresh noodle was found to be a suitable carrier system to deliver viable cells. This is first report on influence of probiotic microcapsules in noodle processing. PMID- 26139870 TI - Optimization of ultrasound-assisted-extraction of porcine placenta water-soluble proteins and evaluation of the antioxidant activity. AB - Porcine placenta is commonly used in Chinese as a traditional medicine. It has been reported by a number of researchers that the porcine placenta contains many compounds which have good health benefits. Response surface methodology (RSM) was applied to optimize the parameters of ultrasound power, ultrasound treat time, and extraction temperature on the extraction yield of porcine placenta water soluble proteins (PPWP). The results indicated that, under optimum conditions of ultrasound power 257 w, extraction temperature at 49 degrees C for 7 min, the extraction yield of PPWP was 32.7 %, which was significantly higher than that of the conventional extraction method (CEM) of 15.0 %. The experimental data were fitted to a second-order polynomial equation using multiple regression analysis and the estimated model showed a high capacity of predicting the dependent variables. Although not significantly, the antioxidant activity of PPWP from ultrasound-assist-extraction (UAE) were higher than those from CEM, indicated that UAE had a positive effect or at least no negative effect on the bioactivity of PPWP. PMID- 26139871 TI - Enhancing antioxidant activity, microbial and sensory quality of mango (Mangifera indica L.) juice by gamma-irradiation and its in vitro radioprotective potential. AB - Gamma irradiation is an effective method currently being used for microbial decontamination and insect disinfestations of foods. In the present study, mango (Mangifera indica L.) juice was irradiated at doses of 0, 1.0, 3.0 and 5.0 kGy and microbial load, total polyphenols, flavonoids, ascorbic acid content, antioxidant activities, colour and sensory properties were evaluated immediately after irradiation and also during storage. Microbiological assay of the fresh and stored mango juice showed better quality after gamma-irradiation. The total polyphenols and flavonoids were significantly (p < 0.05) increased while the ascorbic acid content decreased with the irradiation doses applied. As a result of gamma-irradiation, a significant increment in gallic, syringic and chlorogenic acids and a significant reduction in ferulic and synapic acids were noted when analyzed by HPLC. In vitro antioxidant potentials were measured using DPPH, FRAP and NO scavenging assays; the results showed significant enhancement in the activities after irradiation, that correlated well with the increase in phenolic and flavonoid content. gamma-irradiation improved the colour of mango juice without any adverse changes in the sensory qualities. Significant in vitro plasmid DNA protection was observed in the presence of mango juice against radiation induced damage, even at the dose of 5 kGy. This study confirmed the potential of gamma-irradiation as a method for microbial decontamination and improving the quality of the mango juice without compromising on the sensory attributes. PMID- 26139872 TI - Physico-chemical, nutritional and infrared spectroscopy evaluation of an optimized soybean/corn flour extrudate. AB - A central composite design using RMS (Response Surface Methodology) successfully described the effect of independent variables (feed moisture, die temperature and soybean proportion) on the specific parameters of product quality as expansion index (EI), water absorption index (WAI), water solubility index (WSI) and total color difference (DeltaE) studied. The regression model indicated that EI, WAI, WSI and DeltaE were significant (p < 0.05) with coefficients of determination (R(2)) of 0.7371, 0.7588, 0.7622, 0.8150, respectively. The optimized processing conditions were obtained with 25.8 % feed moisture, 160 degrees C die temperature and 58 %/42 % soybean/corn proportion. It was not found statistically changes in amino acid profile due to extrusion process. The electrophoretic profile of extruded soybean/corn mix presented low intensity molecular weight bands, compared to the unprocessed sample. The generation of low molecular weight polypeptides was associated to an increased in In vitro protein digestibility (IVPD) of the extrudate. The FTIR spectra of the soybean/corn mix before and after extrusion showed that the alpha-helix structure remained unchanged after extrusion. However, the band associated with beta-sheet structure showed to be split into two bands at 1624 and 1640 cm(-1) . The changes in the beta-sheet structures may be also associated to the increased in IVPD in the extruded sample. PMID- 26139873 TI - Physico-chemical properties of acetylated starches from Indian black gram (Phaseolus mungo L.) cultivars. AB - Starches separated from three black gram cultivars were modified by acetylation and compared to their native starches. Acetylation was carried out by treating starches with 0.04 and 0.08 g of acetic anhydride/g of starch dry weight basis (db) at 25 degrees C. The extent of acetylation increased proportionally with the concentration of acetic anhydride used. Retrogradation of acetylated starch pastes decreased significantly (p <= 0.05) as revealed by significant decrease in syneresis, increased freeze thaw stability and increased light transmittance. The pasting curves of 10.7 % starch slurries showed that acetylation decreased the setback viscosity values by 51.2-82.8 % and pasting temperature by 3.1-5.6 degrees C than respective native starches. Differential scanning calorimetry observations also revealed significant decrease in gelatinisation temperature of acetylated starches than native starches. Hardness and adhesiveness of starch gels varied between 10.3 and 32.6 g and 4.6-82.3gs, respectively which were significantly lower than corresponding native starch gels. PMID- 26139874 TI - Effect of modified atmospheric packaging on the shelf life of Kalakand and its influence on microbial, textural, sensory and physico-chemical properties. AB - Kalakand, a popular traditional milk sweet of Indian sub-continent, was packaged under air and modified atmospheric packaging (MAP) conditions (98 % N2, 98 % CO2 and 50 % N2: 50 % CO2). The samples were stored at 10, 25 and 37 degrees C and evaluated for various physico-chemical, microbial, textural and sensory changes, in order to establish the applicability of MAP for storage of Kalakand. It could be established that the MAP conditions of 50 % N2: 50 % CO2and storage at 10 degrees C, were the most suitable conditions for preserving the Kalakand for upto 60 days. PMID- 26139875 TI - Physicochemical properties of modified citrus pectins extracted from orange pomace. AB - Modified pectin is a polysaccharide rich in galacturonic acid altered by pH adjustment and thermal treatment used especially as an anti-cancer agent. The aim of this work was to study the physical and chemical properties of modified pectins extracted from orange pomace with citric and nitric acids. The galacturonic acid content, degree of esterification, Fourier Transform Infrared Spectroscopy profile, molecular weight, intrinsic viscosity, rheological properties and antioxidant activity of the pectins were evaluated. The modification process caused the de-esterification of pectins and a decrease of molecular weight due to removal of neutral sugars, maintaining the linear chain of galacturonic acid. Such changes also caused a significant increase in the in vitro antioxidant activity (p <= 0.05) and influenced the rheological properties of pectin, reducing its viscosity. This work showed that the modification of pectin from orange pomace with citric and nitric acids altered its structural and physical characteristics as well as its biological activity toward a free radical. PMID- 26139876 TI - Optimization of barrel temperature and kidney bean flour percentage based on various physical properties of extruded snacks. AB - The aim of the experiment was to optimize barrel temperature (122 to 178 +/- 0.5 degrees C) and red kidney bean flour percentage (KBF) (12 to 68 +/- 0.5 %) based on physical properties of extrudates like flash off percentage, water absorption index (WAI), water solubility index (WSI), bulk density (BD), radial expansion ratio (RER) and overall acceptability (OAA) using single screw extruder. The study was carried out by central composite rotatable design (CCRD) using Response surface methodology (RSM) and moisture content of feed was kept as constant 16.0 +/- 0.5 % throughout experiments. Mathematical models for various responses were found to fit significantly (P < 0.05) for prediction. Optimization of experimental conditions was carried out using numerical optimization technique and the optimum barrel temperature and kidney bean flour percentage were 120 degrees C (T1) & 142.62 degrees C (T2 = T3) and 20 % respectively with desirability value of 0.909. Experiments were carried out using predicted values and verified using t-test and coefficient of variation percentage. Extruded snack prepared with rice flour (80 %) and kidney bean flour (20 %) at optimized conditions was accepted by the taste panellists and above 20 % KB incorporation was found to decrease overall acceptability score. PMID- 26139877 TI - Selection of enhanced antimicrobial activity posing lactic acid bacteria characterised by (GTG)5-PCR fingerprinting. AB - The aim of the study was a detail evaluation of genetic diversity among the lactic acid bacteria (LAB) strains having an advantage of a starter culture in order to select genotypically diverse strains with enhanced antimicrobial effect on some harmfull and pathogenic microorganisms. Antimicrobial activity of LAB was performed by the agar well diffusion method and was examined against the reference strains and foodborne isolates of Bacillus cereus, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. Antifungal activity was tested against the foodborne isolates of Candida parapsilosis, Debaromyces hansenii, Kluyveromyces marxianus, Pichia guilliermondii, Yarowia lipolytica, Aspergillus brasiliensis, Aspergillus versicolor, Cladosporium herbarum, Penicillium chrysogenum and Scopulariopsis brevicaulis. A total 40 LAB strains representing Lactobacillus (23 strains), Lactococcus (13 strains) and Streptococcus spp. (4 strains) were characterised by repetitive sequence based polymerase chain reaction fingerprinting which generated highly discriminatory profiles, confirmed the identity and revealed high genotypic heterogeneity among the strains. Many of tested LAB demonstrated strong antimicrobial activity specialised against one or few indicator strains. Twelve LAB strains were superior in suppressing growth of the whole complex of pathogenic bacteria and fungi. These results demonstrated that separate taxonomic units offered different possibilities of selection for novel LAB strains could be used as starter cultures enhancing food preservation. PMID- 26139878 TI - The physicochemical properties of legume protein isolates and their ability to stabilize oil-in-water emulsions with and without genipin. AB - The physicochemical and emulsifying properties of legume protein isolates prepared from chickpea (CPI), faba bean (FPI), lentil (LPI) and soy (SPI) were investigated in the presence and absence of genipin. Solubility was highest for CPI (~94 %), followed by LPI (~90 %), FPI (~85 %) and SPI (~50 %). Surface characteristics revealed similar zeta potentials (~ - 47 mV) for CPI, LPI and FPI, but lower for SPI (~ - 44 mV). Contrastingly, surface hydrophobicity was greatest for CPI (~137 arbitrary units, AU), followed by SPI/LPI (~70 AU) and FPI (~24 AU). A significant (from 16.73 to ~8.42 mN/m) reduction in interfacial tension was observed in canola oil-water mixtures in the presence of non crosslinked legume protein isolates. The extent of legume protein isolate-genipin crosslinking was found to be similar for all isolates. Overall, creaming stability increased in the presence of genipin, with maximum stability observed for SPI (65 %), followed by FPI (61 %), LPI (56 %) and finally CPI (50 %). PMID- 26139879 TI - The influence of different polymers on viability of Bifidobacterium lactis 300b during encapsulation, freeze-drying and storage. AB - Seven different types of natural polymers namely hydroxypropyl methylcellulose (HPMC), sodium-carboxymethyl cellulose (Na-CMC), microcrystalline cellulose (MCC), starch BR-07, starch BR-08, dextrin and pullulan were used in order to develop the optimal formula for the entrapment of Bifidobacterium lactis 300B in Ca-alginate based granules. Laminar flow drip casting with Brace-Encapsulator was used in order to prepare the granules. The results showed that alginate/pullulan and alginate/HPMC formulation provide high protection for the bacterial strain used for encapsulation. These two formulations were further used to obtain freeze dried granules, for which the viability in time and at different temperatures was tested. The final results showed a higher viability than the level of the therapeutic minimum (>10(7) CFU/g) after 15 days of storage. Other parameters like entrapment efficiency, production rate, sphericity, flowability were also discussed. PMID- 26139880 TI - Development and analysis of composite flour bread. AB - The study elucidates the effect of utilizing cereal-pulse-fruit seed composite flour in the development and quality analysis of leavened bread. The composite flour was prepared using refined wheat flour (WF), high protein soy flour (SF), sprouted mung bean flour (MF) and mango kernel flour (MKF). Three variations were formulated such as V-I (WF: SF: MF: MKF = 85:5:5:5), V-II (WF: SF: MF: MKF = 70:10:10:10), and V-III (WF: SF: MF: MKF = 60:14:13:13). Pertinent functional, physico-chemical and organoleptic attributes were studied in composite flour variations and their bread preparations. Physical characteristics of the bread variations revealed a percentage decrease in loaf height (14 %) and volume (25 %) and 20 % increase in loaf weight with increased substitution of composite flour. The sensory evaluation of experimental breads on a nine-point hedonic scale revealed that V-I score was 5 % higher than the standard bread. Hence, the present study highlighted the nutrient enrichment of bread on incorporation of a potential waste material mango kernel, soy and sprouted legume. Relevant statistical tests were done to analyze the significance of means for all tested parameters. PMID- 26139881 TI - A higher sensitivity and efficiency of common primer multiplex PCR assay in identification of meat origin using NADH dehydrogenase subunit 4 gene. AB - A Common Primer Multiplex PCR (CP-M-PCR) was developed to detect meat origin of four groups of animal (pig, ruminant, avian and rabbit). This method demonstrated higher sensitivity and efficiency than the conventional multiplex PCR. In this approach, a common forward primer was designed in the 5' end of a homologous region of mitochondrial NADH dehyrogenase subunit 4 (Nad 4) gene sequences of all the animal groups. Specific adapter reverse primers were designed by adding an adapter sequence at the 5' end. The same adapter sequence was used as the common adapter reverse primer. The primers generated specific fragments of 267, 370, 504, and 548 bp lengths for pig, ruminant, avian and rabbit meats, respectively. The use of adapter sequence at the 5' end of the common adapter reverse primers increased the efficiency of the amplification and the application of a common forward primer solved the complexity in multiplex PCR system. Bands of specific amplification can be detected in the PCR assays containing as low as 10(-6) MUM of adapter reverse primer. This result indicated that the sensitivity was tremendously increased as compared to the conventional multiplex PCR (10(-3) MUM). CP-M-PCR detection limit of the DNA samples was 0.1 ng for the four groups of meats. CP-M-PCR has greatly improved the sensitivity and efficiency of the PCR system for a more reliable and accurate outcome than conventional multiplex PCR system. PMID- 26139882 TI - Effect of acetyl esterification on physicochemical properties of chick pea (Cicer arietinum L.) starch. AB - Acetyl esterification of isolated Bengal gram starch was carried out using acetic anhydride as reactant. Modification of native starch at variant concentrations of acetic anhydride (6, 8 and 10 %, w/w) resulted in modified starch with 2.14, 3.35, 4.47% acetyl content and 0.082, 0.130 and 0.176 degrees of substitution (DS) respectively. The acetyl esterification of native starch brought significant changes in physicochemical properties with respect to pasting behavior, granule morphology, thermal properties and retrogradation profile. Acetyl modifications of native starch increased swelling capacity, water absorption power and oil absorption capability by 17, 13 and 20 % respectively. Acetylation has decreased pasting temperature, pasting time, final viscosity and set back viscosity due to increase in amylsoe content, hydrogen bonding and porosity of starch granule. The acetyl modification was confirmed by IR spectra with the presence of an ester carbonyl group (C = O) at 1720.3 cm(-1) and absorption band at 174.8 cm(-1). In DSC evaluation there was decrease in To, Tp, Tc and DeltaH of acetylated starch than native starch which resulted in reduced retrogradation by 56 %. PMID- 26139883 TI - Small deformation viscoelastic and thermal behaviours of pomegranate seed pips CMC gels. AB - The current investigation presents an exploration in phase behaviour of carboxymethyl cellulose (CMC) produced from pomegranate seed pips compared to low and high viscosity CMCs (LMCMC and HMCMC) primarily at low solid concentrations. Cellulose was extracted with 10 % NaOH at 35 degrees C for 22 h from pomegranate seed pips and converted to CMC by etherification process. Thermomechanical analysis and micro-imaging were carried out using small deformation dynamic oscillation in shear, modulated differential scanning calorimetry (MDSC) and scanning electron microscopy (SEM). The results emphasize the importance of molecular interaction and the degree of substitution in produced CMC. Thermal gravimetric analysis (TGA) thermograms showed an initial weight loss in pomegranate seed pips CMC (PSCMC) sample, which we attribute to presence of amount of moisture in sample powder. MDSC analysis of PSCMC showed five different peaks at 84, 104, 173, 307 and 361 degrees C. Moreover, G' and G" changes were found to be dependent on both concentration and frequency. The results of frequency sweep and tan delta indicate that PSCMC solutions can be classified as weak gels. PMID- 26139884 TI - Effect of six different cooking techniques in the nutritional composition of two fish species previously selected as optimal for renal patient's diet. AB - Benefits of fish consumption are widely known, but there is little information about nutrient values of raw and cooked fish. The aim was to study the impact that six cooking techniques have on the nutritional composition of two fish species with low content of adverse nutrients in renal diet. Raw and steamed, foiled with aluminum, foiled with banana leaf, gas oven-baked, microwave oven coked and fried lightly samples were chemically analyzed to determine their protein, phosphorus and lipid content. Crevalle jack: all methods increased lipid and protein content and fatty acids (FA) varied in all cooking methods. Phosphorus decreased in the steamed and microwave oven-cooked samples. Red drum: foiled and fried lightly increased lipid content compared to the raw sample. FA concentration changed in all cooking methods. Protein increased with every technique and phosphorus decreased in the steamed and gas oven-baked samples. Renal patients should preferably consume crevalle jack steamed or microwave oven cooked and red drum steamed or gas oven-baked. PMID- 26139885 TI - Production of beta-galactosidase from streptococcus thermophilus for galactooligosaccharides synthesis. AB - Efficiency of different methods for disruption of Streptococcus thermophilus cells, isolated from different dairy products, to release beta-galactosidase and synthesis of GOS by extracted enzyme using whey supplemented with different concentrations of lactose as a substrate was studied. Unlike most other studies on GOS synthesis which used only one method of cell disruption and only few microbial strains, we compared five different cell disruption methods and used 30 strains of S. thermophilus in order to find out the most effective method and efficient strain for production of beta-galactosidase. Appreciable amount of GOS (53.45 gL(-1)) was synthesized at a lactose concentration of 30 %, using enzyme (10 U mL(-1) of reaction medium), extracted from S. thermophilus within a very short incubation time of 5 h at a temperature of 40 degrees C and pH 6.8. S. thermophilus is heavily employed in the preparation of fermented dairy products but this study extends the use of this organism for the production of GOS, a potential prebiotic. PMID- 26139886 TI - A Novel cooked extruded lentils analog: physical and chemical properties. AB - Developing an extruded lentil analog is our aim. Lentil analog with six formulations were produced using a pilot-scale single (SS) and twin screw (TS) extruders. Texture analysis of lentil analogs prepared for consumption revealed that the products formulated with 60:40 and 70:30 soy: wheat ratios exhibited a significantly higher hardness, adhesiveness and lower springiness as compared to all other treatments. Differential Scanning Calorimeter (DSC) results indicated that all starches in dry blend are completely 100 % gelatinized by extrusion for all treatments at 100 degrees C. The maximum peak of viscosity for TS was formed after 5.58 min. from the run at 89.9 degrees C for the best treatment. However, this lentil analog product can provide a high quality lentil which can be used as a substitute for regular lentils. PMID- 26139887 TI - The effects of copper-glycine complexes on chemical composition and sensory attributes of raw, cooked and grilled chicken meat. AB - To determine the influence of glycine-Cu chelates (Gly-Cu) on chemical composition and sensory characteristic of chickens meat, two hundred of Ross 308 broilers were fed diets containing 16 mg kg(-1) of copper sulfate (S-Cu; control group) or 16, 8 and 4 mg/kg of Cu-glycine chelate (Gly-Cu). The chemical composition was determined in crude and prepared (cooked and grilled) breast and thigh samples. No significant influence of Gly-Cu on the content of the protein, fat and ash in the breast meat was found. Substituting S-Cu with Gly-Cu at different doses in feed did not significantly modify the fatty acids profile of the meat. The breast meat from chickens administered with Gly-Cu contained significantly less cholesterol than that in S-Cu. No different effect of the experimental agent was observed regarding the content of Cu, Zn and Ca in the breast meat, while in chickens from all the groups administered Gly-Cu there was more significantly Fe (P < 0.01) in comparison with the S-Cu group. The thigh meat revealed significantly (P < 0.01) higher levels of Zn and Ca in comparison with the 16 mg S-Cu group. No significant effect of the diet on the sensory characteristics of the meat was observed. PMID- 26139889 TI - Computational approaches for the classification of seed storage proteins. AB - Seed storage proteins comprise a major part of the protein content of the seed and have an important role on the quality of the seed. These storage proteins are important because they determine the total protein content and have an effect on the nutritional quality and functional properties for food processing. Transgenic plants are being used to develop improved lines for incorporation into plant breeding programs and the nutrient composition of seeds is a major target of molecular breeding programs. Hence, classification of these proteins is crucial for the development of superior varieties with improved nutritional quality. In this study we have applied machine learning algorithms for classification of seed storage proteins. We have presented an algorithm based on nearest neighbor approach for classification of seed storage proteins and compared its performance with decision tree J48, multilayer perceptron neural (MLP) network and support vector machine (SVM) libSVM. The model based on our algorithm has been able to give higher classification accuracy in comparison to the other methods. PMID- 26139888 TI - Characterization of selenium-enriched wheat by agronomic biofortification. AB - Agronomic biofortification of staple crops is an effective way to enhance their contents in essential nutrients up the food chain, with a view to correcting for their deficiencies in animal or human status. Selenium (Se) is one such case, for its uneven distribution in the continental crust and, therefore, in agricultural lands easily translates into substantial variation in nutritional intakes. Cereals are far from being the main sources of Se on a content basis, but they are likely the major contributors to intake on a dietary basis. To assess their potential to assimilate and biotransform Se, bread and durum wheat were enriched with Se through foliar and soil addition at an equivalent field rate of 100 g of Se per hectare (ha), using sodium selenate and sodium selenite as Se supplementation matrices, in actual field conditions throughout. Biotransformation of inorganic Se was evaluated by using HPLC-ICP-MS after enzymatic hydrolysis for Se-species extraction in the resulting mature wheat grains. Selenomethionine and Se(VI) were identified and quantified: the former was the predominant species, representing 70-100 % of the total Se in samples; the maximum amount of inorganic Se was below 5 %. These results were similar for both supplementation methods and for both wheat varieties. Judging from the present results, one can conclude that agronomic biofortification of wheat may improve the nutritional quality of wheat grains with significant amounts of selenomethionine, which is an attractive option for increasing the Se status in human diets through Se-enriched, wheat-based foodstuff. PMID- 26139890 TI - Development of stable flaxseed oil emulsions as a potential delivery system of omega-3 fatty acids. AB - The objective of the present study was to develop a stable flaxseed oil emulsion for the delivery of omega-3 (omega-3) fatty acids through food fortification. Oil in-water emulsions containing 12.5 % flaxseed oil, 10 % lactose and whey protein concentrate (WPC)-80 ranging from 5 to 12.5 % were prepared at 1,500, 3,000 and 4,500 psi homogenization pressure. Flaxseed oil emulsions were studied for its physical stability, oxidative stability (peroxide value), particle size distribution, zeta (zeta)-potential and rheological properties. Emulsions homogenized at 1,500 and 4,500 psi pressure showed oil separation and curdling of WPC, respectively, during preparation or storage. All the combinations of emulsions (homogenized at 3,000 psi) were physically stable for 28 days at 4-7 oC temperature and did not show separation of phases. Emulsion with 7.5 % WPC showed the narrowest particle size distribution (190 to 615 nm) and maximum zeta (zeta) potential (-33.5 mV). There was a slight increase in peroxide value (~20.98 %) of all the emulsions (except 5 % WPC emulsion), as compared to that of free flaxseed oil (~44.26 %) after 4 weeks of storage. Emulsions showed flow behavior index (n) in the range of 0.206 to 0.591, indicating higher shear thinning behavior, which is a characteristic of food emulsions. Results indicated that the most stable emulsion of flaxseed oil (12.5 %) can be formulated with 7.5 % WPC-80 and 10 % lactose (filler), homogenized at 3,000 psi pressure. The formulated emulsion can be used as potential omega-3 (omega-3) fatty acids delivery system in developing functional foods such as pastry, ice-creams, curd, milk, yogurt, cakes, etc. PMID- 26139891 TI - Chitosan extracted from mud crab (Scylla olivicea) shells: physicochemical and antioxidant properties. AB - The aim of this study is to report the yield of extraction, as well as the physicochemical and antioxidant properties of extracted chitosan from mud crabs (S.olivacea) as compared to commercial chitosan. The yield obtained for extracted chitosan was 44.57 +/- 3.44 % with a moisture and ash content of 9.48 +/- 0.59 % and 5.97 +/- 0.90 %, respectively. Commercial chitosan demonstrated a higher degree of deacetylation (58.42 +/- 2.67 %), water (250 +/- 9.90 %) and fat (329 +/- 7.07 %) binding capacity, solubility (73.85 %), viscosity (463.25 +/- 13.10 %) and also the whiteness value (77.8 +/- 0.47) compared to the extracted chitosan, which were only 53.42 +/- 0.88 %, 180 +/- 0.00 %, 260 +/- 0.00 %, 53.38 %, 383.9 +/- 28.43 % and 62.1 +/- 7.52 %, respectively. The structure of extracted and commercial chitosan was also investigated using Fourier Transform Infrared Spectroscopy (FTIR). In conclusion, the extracted chitosan possessed potential properties similar to the commercial chitosan with high reducing power but low in the scavenging activity on the DPPH and hydroxyl radicals compared to the commercial chitosan. PMID- 26139892 TI - Effect of banana flour, screw speed and temperature on extrusion behaviour of corn extrudates. AB - Effect of extrusion parameters (banana flour, screw speed, extrusion temperature) on extrusion behaviour of corn grit extrudates were studied. Second order quadratic equations for extrusion properties as function of banana flour (BF), screwspeed (SS) and extrusion temperature (ET) were computed. BF had predominant effect on the Hunter color (L*, a*, b*) parameters of the extrudates. Addition of BF resulted in corn extrudates with higher L* and lower a* and b* values. Higher ET resulted in dark colored extrudates with lower L* and a* value. Higher SS enhanced the lightness of the extrudates. Expansion of the extrudates increased with increase in the level of BF and ET. WAI of the extrudates decreased with BF whereas increased with SS. However, reversed effect of BF and SS on WSI was observed. Flextural strength of the extrudates increased with increase in SS followed by BF and ET. The addition of BF and higher ET resulted in extrudates with higher oil uptake. PMID- 26139893 TI - Development and validation of a comprehensive model for map of fruits based on enzyme kinetics theory and arrhenius relation. AB - MAP is a dynamic system where respiration of the packaged product and gas permeation through the packaging film takes place simultaneously. The desired level of O2 and CO2 in a package is achieved by matching film permeation rates for O2 and CO2 with respiration rate of the packaged product. A mathematical model for MAP of fresh fruits applying enzyme kinetics based respiration equation coupled with the Arrhenious type model was developed. The model was solved numerically using MATLAB programme. The model was used to determine the time to reach to the equilibrium concentration inside the MA package and the level of O2 and CO2 concentration at equilibrium state. The developed model for prediction of equilibrium O2 and CO2 concentration was validated using experimental data for MA packaging of apple, guava and litchi. PMID- 26139894 TI - Isolation and characterization of collagen from fish waste material- skin, scales and fins of Catla catla and Cirrhinus mrigala. AB - The collagen of skin, scales and fins of Catla catla and Cirrhinus mrigala were isolated and characterised. Nine fishes of each fish species of three weight groups were collected from a commercial fish farm. Collagen characterisation using SDS-PAGE revealed the molecular weights (kDa) of the C. catla skin, scales, and fins which ranged from 120 to 210, 70 to 201, and 68 to 137 kDa, respectively. The size of the collagen of C. mrigala skin, scales and fins ranged from 114 to 201, 77 to 210, and 70 to 147 kDa, respectively. Glycine and alanine were the most abundant amino acid, whereas tryptophan was totally absent in all selected tissues. Thus, significant variation exists in type of collagen and amino acid profile within the weight groups of the two fish species. The imino acid (proline and hydroxyproline) contents estimated in C. catla and C. mrigala skin (161-165 and 160-168), scales (155-159 and 152-161) and fins (162-171 and (152-155) residues/1,000 residues, respectively. The proximate analysis was also performed for skin, scales and fins. The maximum protein content of the skin was determined as 26.10 % and 22.90 % in the C. catla and C. mrigala, respectively, from the W3 weight group. The scales of the W3 weight group exhibited maximum protein contents of 25.90 and 21.77 % for C. catla and C. mrigala, respectively. The maximum protein contents (19.04 % and 18.12 %) were recorded for C. catla and C. mrigala, respectively in the fins. PMID- 26139895 TI - Safety and quality parameters of ready-to-cook minced pork meat products supplemented with Helianthus tuberosus L. tubers fermented by BLIS producing lactic acid bacteria. AB - The aim of this study was to evaluate the influence of additives of Jerusalem artichoke (JA), fermented with P. acidilactici KTU05-7, P. pentosaceus KTU05-9, L. sakei KTU05-6, on the quality and safety parameters of ready - to cook - minced pork (RCMP). Fermented JA additives reduced pH of the meat products and decreased water holding capacity (WHC) from 2.01 till 2.93 %. Concentrations of biogenic amines in RCMP with additives of the lactic acid bacteria (LAB) - fermented JA were significantly lower comparing with control sample. The number of pathogenic bacteria in artificially contaminated meat samples was significantly reduced in case of LAB-fermented JA additives. The highest antimicrobial activity was obtained using P. acidilactici fermented JA additives. The amounts of microbial pathogens E. coli and Ent. faecalis, S. aureus and Streptococcus spp. were determined 3.41, 3.38, 3,96 and 4.74 log CFU/g correspondingly, whereas without LAB-fermented JA additives were 8.94, 7.75, 8.82 and 8.58 log CFU/g, correspondingly. A possibility to improve sensory properties (flavor) of RCMP using LAB fermented JA additives was investigated. The composition of volatile compounds of RCMP without additive and with LAB-fermented JA additives was analyzed using gas chromatography-mass spectrometry (GC-MS). The results of sensory evaluation of meat products supplemented with fermented JA additives revealed specific odor, which is pleasant and acceptable for consumers might be explainable that LAB-fermented JA additives have shown considerable differences mainly due to the accumulation of volatiles such as toluene, ethylbenzene, decane, undecane, 2 methyl undecane. N-morpholinomethyl-isopropyl sulfide, 6-undecilamine and N,N-dimethyl-1-pentadecanamine were not determined in RCMP with LAB-fermented JA additives. The results obtained show, that P. acidilactici fermented JA 5 % additive is most suitable for the RCMP processing in order to prevent microbiological spoilage, increase volatile compounds and acceptability of the products. PMID- 26139896 TI - Volatile compounds of Van Herby cheeses produced with raw and pasteurized milks from different species. AB - Levels of volatile compounds in Van herby cheeses manufactured from raw and pasteurized; 100 % ewes', 50 % ewes'+50 % cows' and mixture of 50 % ewes'+25 % cows'+25 % goats' milks were investigated over 180 days of ripening at 4 degrees C. The volatile compounds levels of herby cheese samples increased throughout the 180 days storage period. Samples produced from pasteurized milk showed lower volatile contents than their counterparts produced from raw milk. The volatile compounds profile of herby cheese samples detected by headspace solid-phase microextraction (HS-SPME) consisted of 8 esters, 5 ketones, 5 aldehydes, 9 acids, 6 alcohols and 14 hydrocarbons and terpenes. Acetic acid was the most abundant volatile compound in HS-SPME of ripened cheeses, followed by hexanoic, octanoic and butanoic acids. PMID- 26139897 TI - Optimization of starch isolation from taro using combination of enzymes and comparison of properties of starches isolated by enzymatic and conventional methods. AB - The optimization of enzymatic starch isolation process from taro tubers using cellulase and xylanase was carried out. The functional properties of starch isolated by optimized enzymatic process were compared with starch isolated by conventional method without the use of enzymes. A central composite rotatable design (CCRD) with four numerical factors was employed to design the experiments. The numerical factors were cellulase concentration (0-100 U/100 g tuber), xylanase concentration (0-100 U/100 g tuber), temperature of incubation (30-50 degrees C) and incubation time (1-5 h). Statistical analysis showed that the main effects of all the factors were significant on starch yield and effect of cellulase was more significant compared to xylanase. The effectiveness of xylanase in increasing the yield of starch from taro tubers confirmed that xylan is an important component of the cell walls of taro tubers. The optimized condition with maximum starch yield (17.22 %) was obtained when cellulase and xylanase concentration were 299.86 and 300 U/100 g tuber, temperature was 35 degrees C and incubation time was 2 h. The swelling of the starch granules increased whereas solubility decreased for enzymatic method. The clarity of the starch paste isolated by enzymatic method was found to be better compared to the clarity of starch paste isolated by conventional method. The pasting temperature of the starch paste was slightly higher and viscosity was lower for the starch isolated by enzymatic method. Freeze-thaw stability of the starch paste was also found to be better for the enzymatically isolated starch. PMID- 26139898 TI - Nitrite-free Asian hot dog sausages reformulated with nitrite replacers. AB - This research deals with the application of a global strategy designed to produce a nitrite-free Asian hot dog. Different ingredients such as annatto, cochineal, orange dietary fibre, vitamins E and C, lactate and celery were combined in order to study the appearance (colour), lipid oxidation stability and microbial stability of the nitrite-free formulations. The control sample contained much more (P < 0.05) residual nitrite (88.7 mg/kg) than the samples without added nitrite (23-24 mg/kg). Generally, no formulation-dependent variations were observed in fat and water binding properties. Control sample had the highest L* and a* values, while the product with annatto (RA) had the lowest a* values. Lipid oxidation levels were similar irrespective of formulation. The hot dog reformulated with cochineal (RC) scored higher for overall acceptability than RA, mainly due to its colour. PMID- 26139899 TI - Analysis of DPPH inhibition and structure change of corn peptides treated by pulsed electric field technology. AB - In this study, the effects on antioxidant activity and structure change of corn peptides (CPS) with 10 to 30 kDa molecular weight (MW) treated by pulsed electric field (PEF) technology were investigated. 2, 2-diphenyl-1-picrylhydrazyl (DPPH) inhibition was used to evaluate the antioxidant activity of CPS. Response surface methodology (RSM) was used to investigate the effects of PEF treatment parameters on antioxidant activity of CPS. The optimal conditions were as follows: concentration of CPS 10 mg mL(-1), electric field intensity 15 kV cm(-1), and pulse frequency 2,000 Hz. Under the optimized conditions, the DPPH inhibition of CPS increased 32.1 %, compared to the sample untreated. And mid-infrared spectroscopy (MIR) was used for analyzing the structure change of CPS. The results showed that PEF technology could obviously increase the DPPH inhibition of CPS under the optimized conditions (P < 0.05). PMID- 26139900 TI - Individual shrink wrapping extends the storage life and maintains the antioxidants of mango (cvs. 'Alphonso' and 'Banganapalli') stored at 8 degrees C. AB - Freshly-harvested mature green mangoes (cvs. 'Alphonso' and 'Banganapalli') were individually shrink wrapped using two semi-permeable Cryovac films(r) (D-955 and LD-935) and a locally available LDPE film. The shrink wrapped and non-wrapped fruit were stored at 8 degrees C for 5 weeks and transferred to ambient conditions for subsequent ripening, to study the feasibility of alleviation of chilling injury (CI) and to determine shrink wrapping effect on fruit quality. Shrink wrapped mangoes of 'Banganapalli' and 'Alphonso' cultivars packed in D-955 (15 MUm thickness) film could be stored for 5 weeks at 8 degrees C in fresh and unripe green condition. After storage, these cultivars respectively lost only 0.5 and 1.4 % mass in case of shrink wrapping as compared to 5.8 and 6.9 % loss in non-wrapped fruit. After removal from low temperature and unwrapping, shrink wrapped mangoes showed normal respiratory behaviour with production of CO2 and ethylene peaks (climacteric peaks) during ripening, whereas non-wrapped fruit did not show any respiratory peaks. Shrink wrapped mangoes ripened normally within a week at ambient temperature (24-32 degrees C and 60-70 % RH) with good surface yellow colour (reflected by hue and chroma values), edible softness, retention of nutritional quality and acceptable organoleptic quality. These quality parameters were better in fruit wrapped with D-955 film compared to LD-935 and LDPE films. Total carotenoids in terms of beta-carotene content were significantly higher in shrink wrapped fruit when compared to non-wrapped fruit. Among different shrink films, total antioxidant capacity and DPPH radical scavenging abilities were higher in LD-935 wrapped fruit in case of 'Alphonso' cultivar whereas these were on par in LD-935 and D-955 film wrapped fruit in case of 'Banganapalli' cultivar. PMID- 26139901 TI - Sensory and physicochemical evaluation of low-fat chicken mortadella with added native and modified starches. AB - The objective of this work was to evaluate the effect of adding different starches (native and modified) on the physicochemical, sensory, structural and microbiological characteristics of low-fat chicken mortadella. Two formulations containing native cassava and regular corn starch, coded CASS (5.0 % of cassava starch) and CORN (5.0 % of regular corn starch), and one formulation produced with physically treated starch coded as MOD1 (2.5 % of Novation 2300) and chemically modified starch coded as MOD2 (2.5 % of Thermtex) were studied. The following tests were performed: physicochemical characterization (moisture, ash, protein, starch and lipid contents, and water activity); cooling, freezing and reheating losses; texture (texture profile test); color coordinates (L*, a*, b*, C and h); microbiological evaluation; sensory evaluation (multiple comparison and preference test); and histological evaluation (light microscopy). There was no significant difference (p > 0.05) for ash, protein, cooling loss, cohesiveness or in the preference test for the tested samples. The other evaluated parameters showed significant differences (p < 0.05). Histological study allowed for a qualitative evaluation between the physical properties of the food and its microscopic structure. The best results were obtained for formulation MOD2 (2.5 % Thermtex). The addition of modified starch resulted in a better performance than the native starch in relation to the evaluated technological parameters, mainly in relation to reheating losses, which demonstrated the good interaction between the modified starch in the structure of the product and the possibility of the application of this type of starch in other types of functional meat products. PMID- 26139902 TI - Anti-obesity and cardioprotective effects of cinnamic acid in high fat diet- induced obese rats. AB - Obesity is a chronic metabolic disorder that is associated with numerous diseases including hyperlipidemia, diabetes mellitus, hypertension, atherosclerosis, cardiovascular disease, and cancer. Cinnamic acid is a phytochemical compound having many biological effects and could be considered for the management of obesity. This study is aimed to assess the possible anti-obesity and cardioprotective properties of cinnamic acid (CA) in high fat diet-fed rats (HFD). Male Wistar rats were divided into 4 groups. They received normal diet, HFD diet, HFD supplemented with fluvastatin (2 mg/kg/day) or cinnamic acid (30 mg/kg/day) for 7 weeks. The results showed an increase in body weight of HFD rats by ~27 % as compared to control group. Moreover, serum lipase activity underwent a significant rise by 103 % which led to an increase in the levels of total cholesterol (T-Ch), triglycerides (TG), LDL-cholesterol in serum of untreated HFD fed rats. Furthermore, the concentration of leptin and angiotensin-converting enzyme (ACE) activity exhibited remarkable increases in serum of HFD-fed rats as compared to controls. Whereas, the administration of CA to HFD-fed rats improved the body weight gain and serum lipid profile and reverted back near to normal the activities of lipase and ACE. In addition, the echocardiography evidenced that CA is able to protect the aorta and aortic arch and avoided vasoconstriction by increasing their diameters and improved liver steatosis and kidney indices of toxicity. Overall, these results suggest that cinnamic acid exerts anti-obesity and antihypertensive effects through inhibition of lipid digestive enzymes and ACE. PMID- 26139903 TI - Characterization of flaxseed oil emulsions. AB - The emulsifying capacity of surfactants (polysorbate 20, polysorbate 80 and soy lecithin) and proteins (soy protein isolate and whey protein isolate) in flaxseed oil was measured based on 1 % (w/w) of emulsifier. Surfactants showed significantly higher emulsifying capacity compared to the proteins (soy protein isolate and whey protein isolate) in flaxseed oil. The emulsion stability of the flaxseed oil emulsions with whey protein isolate (10 % w/w) prepared using a mixer was ranked in the following order: 1,000 rpm (58 min) ~ 1,000 rpm (29 min) ~ 2,000 rpm (35 min) >2,000 rpm (17.5 min). The emulsion stability of the flaxseed oil emulsions with whey protein isolate (10 % w/w) prepared using a homogenizer (Ultra Turrax) was independent of the speed and mixing time. The mean particle size of the flaxseed oil emulsions prepared using the two mixing devices ranged from 23.99 +/- 1.34 MUm to 47.22 +/- 1.99 MUm where else the particle size distribution and microstructure of the flaxseed oil emulsions demonstrated using microscopic imaging were quite similar. The flaxseed oil emulsions had a similar apparent viscosity and exhibited shear thinning (pseudoplastic) behavior. The flaxseed oil emulsions had L* value above 70 and was in the red-yellow color region (positive a* and b* values). PMID- 26139904 TI - Chemical, rheological and mechanical evaluation of maize dough and tortillas in blends with cassava and malanga flour. AB - Masa or dough from nixtamalized maize with cassava (Cf) and malanga flour (Mf) addition at 20, 30 and 40 % (w/w) were prepared making seven treatments. The produced masas or doughs were subjected to chemical analysis, rheological and mechanical tests. Tortillas were manufactured from these doughs and mechanical tests were undertaken. Doughs from tubers had less protein and lipid content but higher nitrogen free extract than the control. All doughs presented weak viscoelastic gel-like behavior, with those of Mf behaving mainly as viscous systems. Doughs with Cf showed lower decrease in both the elastic (G') and viscous (G") moduli than those with Mf. The adhesiveness and cohesiveness of doughs with Mf showed a higher reduction of maximum force than those with Cf. Tortillas with Cf were more elastic with higher tensile strength than those with Mf. Using Cf as partial substitution of maize might lower production costs, but Mf is not particularly suitable as maize substitute in tortilla production. Tortillas with 40 % (w/w) cassava flour, presented the highest preference on a sensory test. PMID- 26139905 TI - Optimization of antioxidant phenolic compounds extraction from quinoa (Chenopodium quinoa) seeds. AB - The objective of this study was to optimize the extraction conditions of phenolic and flavonoids compounds from quinoa (Chenopodium quinoa) seeds using ultrasound assistance technology. A randomized central composite face-centered design was used to evaluate the effect of extraction temperature, ethanol concentration in the solvent, and ultrasound power on the total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity by response surface analysis. Predicted model equations were obtained to describe the experimental data regarding TPC, TFC and antioxidant activity, with significant variation in the linear, quadratic, and interaction effects of the independent variables. Regression analysis showed that more than 88 % of the variability was explained by the models. The best extraction conditions obtained by simultaneous maximization of the responses were: extraction temperature of 60 degrees C, 80 % ethanol as solvent and non-application of ultrasounds. Under the optimal conditions, the corresponding predicted response values were 103.6 mg GAE/100 g dry weight (dw), 25.0 mg quercetin equiv./100 g dw and 28.6 % DPPH radical scavenging, for TPC, TFC and antioxidant activity, respectively. The experimental values agreed with those predicted within a 95 % confidence level, indicating the suitability of the employed model. HPLC analysis of the obtained extracts confirmed the highest phenolic compound yield in the extract obtained under optimal extraction conditions. Considering the characteristics of the antioxidant rich extracts obtained, they could be consider for potential application in the food industry, as nutraceutical and functional foods ingredient or well as replacement of synthetic antioxidants. PMID- 26139906 TI - Optimization of pneumatic sheet extrusion of whole wheat flour poory dough using response surface methodology. AB - Pneumatic extrusion of whole wheat flour dough is a challenge in the preparation of Poory. In the present study, the pneumatic extrusion process variables (pneumatic pressure, rate of extrusion) and quality of deep fried product (oil uptake, frying time, puffed height) was evaluated to get Poory of maximum overall sensory quality, minimum shear and minimum oil uptake. These parameters depend on the moisture content of wheat dough. Response surface methodology was demonstrated to be an efficient tool for the optimization of process parameters of pneumatic extrusion. The results indicated that extrusion pressure ranging from 3 ~ 6 * 10(5) Pa for the whole wheat flour dough with added moisture of 56 ~ 60 % was found to give a uniform rate of extruded sheet. It was observed that submerged frying time for the extruded dough sheet was in the range of 35 ~ 40 s, with the temperature of the vegetable oil to be in the range of 180 ~ 185 degrees C. Oil uptake during frying was about 12 +/- 1 % and the textural shear force was found to be 9.9 N with an overall sensory score of 7.2 +/- 0.5 on nine point scale. The experimental errors for all attributes were non-significant (p > 0.05) and thus optimum variables predicted by the model are found suitable. PMID- 26139907 TI - Effect of UV irradiation, sample thickness and storage temperature on storability, bacterial activity and functional properties of liquid egg. AB - Effect of sample thickness, ultraviolet irradiation and storage temperature on bacterial activity, storability and functional properties (foamability and stability) of liquid egg were investigated. Eggs were contaminated with prepared Salmonella suspension 108/mL. Separated albumen and yolk samples were poured in three thicknesses (1, 2 and 3 mm) and irradiated at 3, 5 10, 15 min with ultraviolet radiation and were stored at 5, 15, 25, 37 degrees C for up to 8 days. Observations indicated that all ultraviolet irradiation times, reduced the total count of Salmonella bacteria in egg samples. Although, functional properties were improved, protein oxidation in both albumen and yolk increased. After the first 2 days of storage, total counts of Salmonella and protein oxidation of eggs decreased solely in the 5 degrees C treatment. It is concluded that irradiation treatment can be used to decrease bacterial contamination of liquid egg albeit not below the safe level for raw consumption. Furthermore, the best irradiation times to improve foam ability and stability were 10 and 5 min, respectively. PMID- 26139908 TI - Development of gluten free biscuits utilizing fruits and starchy vegetable powders. AB - Gluten free biscuits, also suitable during fasting were developed utilizing different levels of fruits (water chestnut and makhana) and starchy vegetable (potato) powders. Biscuits were developed using creamery method and evaluated for physical properties, proximate composition, sensory characteristics and storability for 90 days at room temperature. Expansion in diameter of biscuits with different level of potato and makhana powder varied between 1.026 to 1.059 and 1.046 to 1.059, respectively as compared to 1.075 for biscuits prepared using water chestnut only. Breaking hardness and toughness of different biscuit was increased with increasing level of potato or makhana powder in flour blends and higher in potato powder incorporated biscuits. Whiteness (L values) of biscuits was decreased with increasing level of potato powder while a reverse trend was observed in case of makhana powder incorporated biscuits. Protein content in biscuits with makhana powder was higher than the biscuits prepared using potato powder in flour blends. Biscuits prepared using hundred percent water chestnut showed the maximum crude fibre content in them. Results indicated that gluten free biscuits for fasting people can be prepared using potato powder or makhana powder up to 50 % with water chestnut powder. The overall sensory acceptability of biscuits with makhana powder was better than for biscuits with potato powder with maximum overall acceptability scores for biscuits developed using 70:30 parts of water chestnut and makhana powders in flour blend, which were storable for 90 days period at room temperature. PMID- 26139909 TI - Quality of shrimp analogue product as affected by addition of modified potato starch. AB - The present study was aimed to investigate the effects of addition of modified potato starch on the biochemical and textural properties of shrimp analogue/imitation shrimp, a popular value-added product prepared from surimi. Three batches of shrimp analogues were prepared with 0 % (NPS), 50 % (CPS) and 100 % (MPS) of modified starch incorporation and various quality attributes were monitored at regular intervals during frozen storage (-20 degrees C). Loss of myofibrillar protein was least for the shrimp analogue sample added with 100 % modified potato starch. The expressible moisture content of MPS (2.48 %) was less affected by long term storage compared to CPS (3.38 %) and NPS (3.99 %). During extended low temperature storage, the textural quality of sea food analogue was highly influenced by the type of starch added to it. The percentage of modified potato starch added to shrimp analogue significantly (p <= 0.05) affected its hardness and fracturability. MPS samples did not show significant changes in hardness during storage as compared to other two samples. Springiness of shrimp analogue increased 2.57, 1.5 and 1.77 times with the storage period for samples with NPS, CPS and MPS, respectively. Addition of modified potato starch improved the sensory quality and textural properties of shrimp analogue and reduced the quality degradation during frozen storage as compared to NPS which contained only native potato starch. PMID- 26139910 TI - Suitable coating material for microencapsulation of spray-dried fish oil. AB - This study was conducted to screen the most suitable coating material for the production of microencapsulated fish oil powder using ternary blends of maltodextrin (15, 25 % w/w), Arabic gum (2.5, 7.5 % w/w), and methylcellulose (0.5, 1.5 % w/w). The physical properties of fish oil emulsion and encapsulated powders were evaluated. Arabic gum (5 % w/w) showed the most significant (p < 0.05) effect on the surface mean diameter of the droplets in the emulsion. Maltodextrin had the most significant (p < 0.05) effect on the centrifuge stability of the emulsion and the amount of surface oil of the powder at 15 and 20 % (w/w) respectively, whereas methylcellulose (0.5 % w/w) had the most significant (p < 0.05) effect on the width distribution of the droplets in the emulsion. The total optimal area leading to the formation of coating material with desirable physical properties was expected to be obtained by the combination of 16 % (w/w) maltodextrin, 6.5 % (w/w) Arabic gum, and 0.88 % (w/w) methylcellulose respectively. PMID- 26139911 TI - Optimization of supercritical fluid extraction of essential oils and fatty acids from flixweed (Descurainia Sophia L.) seed using response surface methodology and central composite design. AB - Essential oils and fatty acids of Descurainia sophia L. seed were obtained by supercritical CO2 extraction and steam distillation methods. The effect of different parameters such as pressure, temperature, modifier volume, dynamic and static extraction timeon the extraction yield were optimized using a central composite design after a 2 (n-1) fractional factorial design. The results showed that under the pressure of 355 bar, temperature of 65 degrees C, methanol volume of 150 MUL, dynamic and static extraction times of 35 and 10 min, respectively, the major components were methyl linoleate (18.2 %), camphor (12.32 %), cis thujone (11.3 %) and trans-caryophyllene (9.17 %). The results indicated that by using the proper conditions, the supercritical fluid extraction is more selective than the steam distillation method. Extraction yields based on supercritical fluid extraction varied in the range of 0.68 to 17.1 % (w/w), and the extraction yield based on the steam distillation was 0.25 % (v/w). PMID- 26139912 TI - Antimicrobial and radical scavenging properties of bovine collagen hydrolysates produced by Penicillium aurantiogriseum URM 4622 collagenase. AB - A 2(3) full factorial design was used to identify the main effects and interactions of pH, collagen concentration and temperature on the degree of collagen hydrolysis (DH) by collagenase from Penicillium aurantiogriseum URM 4622. Increases in both pH and collagen concentration improved DH, and a positive interaction effect was observed for these variables. On the other hand, temperature had a negative main effect on DH. The maximum value of DH (4.65 MUg/mL) was achieved at 7.5 mg/mL collagen concentration, pH 8.0 and 25 degrees C. The peptide profile showed several peptides with molecular weights lower than 2 kDa and exhibited antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. An antioxidant activity of 84.7 +/- 0.24 % towards the radical ABTS* + was obtained with 50 mg/mL hydrolysates. This study demonstrated that collagen hydrolysed by P. aurantiogriseum URM 4622 collagenase possesses interesting antibacterial and antioxidant activities. PMID- 26139914 TI - Functional bread with n-3 alpha linolenic acid from whole chia (Salvia hispanica L.) flour. AB - This work proposed to study the effects of the addition of whole chia flour (WCF) on the technological, nutritional and sensory qualities of bread. Different WCF contents (0 and 20 %) and vital gluten (VG) (0 and 4 %) were added to bread according to a 2(2) central composite rotational design. WCF decreased the specific volume, lightness and hue angle of the bread loaves, but did not affect the chroma values. WCF and VG contributed to maintenance of the moisture content of the loaves during the storage period. The increased firmness found with the addition of high levels of WCF (more than 10 %) was countered by larger amounts of VG (more than 2 %). The optimum loaf (10 % WCF and 2 % VG) showed 26 % more lipids, 19 % more protein and 11 % more ash than the standard loaf (0 % WCF and 0 % VG). A better lipid profile was also found (higher omega-3 fatty acid content and a better omega-6/omega-3 ratio). Both breads were positively rated in the sensory profile analysis. PMID- 26139913 TI - Influence of electrical and hybrid heating on bread quality during baking. AB - Energy efficiency and product quality are the key factors for any food processing industry. The aim of the study was to develop energy and time efficient baking process. The hybrid heating (Infrared + Electrical) oven was designed and fabricated using two infrared lamps and electric heating coils. The developed oven can be operated in serial or combined heating modes. The standardized baking conditions were 18 min at 220 degrees C to produce the bread from hybrid heating oven. Effect of baking with hybrid heating mode (H-1 and H-2, hybrid oven) on the quality characteristics of bread as against conventional heating mode (C-1, pilot scale oven; C-2, hybrid oven) was studied. The results showed that breads baked in hybrid heating mode (H-2) had higher moisture content (28.87%), higher volume (670 cm(3)), lower crumb firmness value (374.6 g), and overall quality score (67.0) comparable to conventional baking process (68.5). Moreover, bread baked in hybrid heating mode showed 28% reduction in baking time. PMID- 26139915 TI - Physical properties of ebony seed (Pithecellobium flexicaule) and functional properties of whole and defatted ebony seed meal. AB - A partial characterization was done of ebony (Pithecellobium flexicaule) seed physical properties, and how defatting affected some functional properties of ebony seed meal. Average seed dimensions were 13.02 mm length, 8.78 mm width and 9.65 mm thickness. Geometric diameter was 10.76 mm, volume was 530 mm(3), surface area was 364.33 mm(2), sphericity was 83.26 % and aspect ratio was 68.24 %. Thousand-seed weight was 0.70 Kg, of which 0.42 Kg (60 %) represented the kernel. Defatted ebony seed meal differed from whole meal in all measured parameters, particularly in its protein (44.72 g/100 g) and carbohydrates (44.12 g/100 g) proportions. The defatted meal had higher water absorption capacity (1.28 g/g sample), water solubility capacity (26.06 %), oil absorption capacity (2.04 g/g sample), emulsifying capacity (53.78 %) and gelling capacity (8 % w/v) than the whole meal. Ebony seed physical properties may prove useful in designing post harvest processing equipment and in quality control. The high protein content of defatted ebony seed meal suggests its use as a natural alternative ingredient in numerous food industry applications. PMID- 26139916 TI - Myocardial potency of Bio-tea against Isoproterenol induced myocardial damage in rats. AB - Kombucha (Bio-tea) is a beverage produced by the fermentation of sugared black tea using a symbiotic association of bacteria and yeasts. Traditional claims about Kombucha report beneficial effects such as antibiotic properties, gastric regulation, relief from joint rheumatism and positive influence on the cholesterol level, arteriosclerosis, diabetes, and aging problems. The present investigation was carried out to understand the preventive effect of Kombucha on heart weight, blood glucose, total protein, lipid profile and cardiac markers in rats with myocardial damage induced using Isoproterenol. As Bio-tea is produced by fermenting tea, the parameters were compared in rats pre-treated with normal black tea and Bio-tea for 30 days followed by subcutaneous injection of Isoproterenol (85 mg/kg body weight). Normal rats as well as Isoproterenol induced myocardial infarcted rats were also used, which served as controls. Isoproterenol induced myocardial infarcted control rats showed a significant increase in heart weight, blood glucose and cardiac markers and a decrease in plasma protein. Increased levels of cholesterol, triglycerides, low density lipids (LDL) and very low density lipids (VLDL) were also observed, while the high density lipid (HDL) content decreased. Bio-tea showed a higher preventive effect against myocardial infarction when compared to tea, as was observed by the significant reduction in heart weight, and blood glucose and increase in plasma albumin levels. Bio-tea significantly decreased cholesterol, triglycerides, LDL and VLDL while simultaneously increasing the levels of HDL. Similarly a decrease in leakage of cardiac markers from the myocardium was also observed. PMID- 26139917 TI - Effect of processing conditions on oil point pressure of moringa oleifera seed. AB - Seed oil expression is an important economic venture in rural Nigeria. The traditional techniques of carrying out the operation is not only energy sapping and time consuming but also wasteful. In order to reduce the tedium involved in the expression of oil from moringa oleifera seed and develop efficient equipment for carrying out the operation, the oil point pressure of the seed was determined under different processing conditions using a laboratory press. The processing conditions employed were moisture content (4.78, 6.00, 8.00 and 10.00 % wet basis), heating temperature (50, 70, 85 and 100 degrees C) and heating time (15, 20, 25 and 30 min). Results showed that the oil point pressure increased with increase in seed moisture content, but decreased with increase in heating temperature and heating time within the above ranges. Highest oil point pressure value of 1.1239 MPa was obtained at the processing conditions of 10.00 % moisture content, 50 degrees C heating temperature and 15 min heating time. The lowest oil point pressure obtained was 0.3164 MPa and it occurred at the moisture content of 4.78 %, heating temperature of 100 degrees C and heating time of 30 min. Analysis of Variance (ANOVA) showed that all the processing variables and their interactions had significant effect on the oil point pressure of moringa oleifera seed at 1 % level of significance. This was further demonstrated using Response Surface Methodology (RSM). Tukey's test and Duncan's Multiple Range Analysis successfully separated the means and a multiple regression equation was used to express the relationship existing between the oil point pressure of moringa oleifera seed and its moisture content, processing temperature, heating time and their interactions. The model yielded coefficients that enabled the oil point pressure of the seed to be predicted with very high coefficient of determination. PMID- 26139918 TI - Effect of different coatings on post-harvest quality and bioactive compounds of pomegranate (Punica granatum L.) fruits. AB - The effect of three different coatings; resin wax (Britex Ti), carnauba wax (Xedasol M14), and chitosan (1 and 2 % w/v) on postharvest quality of pomegranate fruits were investigated. Fruits quality characteristics and bioactive compounds were evaluated during 40, 80 and 120 days storage at 4.5 degrees C and 3 additional days at 20 degrees C. The results showed that uncoated fruits showed higher respiration rate, weight loss, L* and b* values of arils, total soluble solids (TSS)/titratable acidity (TA), and pH than coated fruits during storage. Coating treatments could delay declining TSS and TA percent, a* value of arils, as well as bioactive compounds such as total phenolics, flavonoids and anthocyanins content and antioxidant activity. The coated fruits with commercial resin and carnauba waxes showed significantly lower respiration rate and weight loss than other treatments, however carnauba wax could maintain considerably higher fruits quality and bioactive compounds than other coating treatments. The results suggested that postharvest application of carnauba wax have a potential to extend storage life of pomegranate fruits by reducing respiration rate, water loss and maintaining fruit quality. PMID- 26139919 TI - Development and comparison of shelf stable extended and dehydrated goat meat cubes containing four different legume based binder mixes. AB - A study was undertaken to develop shelf stable hot air oven dried goat meat cubes extended with different legume based binder mixes. Based on preliminary trials, four different formulations containing 80 % meat mince + 10 % Bengal gram based binder mix (HBE), 70 % meat mince + 20 % green gram based binder mix (HGR), 80 % meat mince + 10 % black gram based binder mix (HBL) and 80 % meat mince + 10 % lentil based binder mix (HLE) were selected and subjected to physico-chemical, microbiological and sensory characteristics. Among treatments, HGR showed a significantly higher pH (6.53 +/- 0.01), whereas there was no significant difference in other physico-chemical parameters. Moisture content (10.37 +/- 1.06 %) was highest in HLE, while protein (49.68 +/- 1.78 %) and ash (8.71 +/- 0.30 %) contents were higher in HBL. On texture profile analysis, hardness, gumminess and chewiness parameters were highest for HLE and lowest for HBL. In all treatments, total plate, Staphylococcus aureus and yeast and mold counts were in acceptable range and coliforms were not detected. Scores for sensory attributes of rehydrated cubes were in good to very good range in all treatments, however, higher scores for appearance, flavour, texture, juiciness and overall acceptability were observed in HBL. The dehydrated cubes could be used to prepare curry within few minutes and is a boon to busy housewives. PMID- 26139920 TI - Importance of solvent association in the estimation of antioxidant properties of phenolic compounds by DPPH method. AB - The presented paper shows the influence of temperature increase in the range typically used during antioxidant measurements (15-35 degrees C) on the estimation of antioxidant properties of phenolic compounds (caffeic acid, ferulic acid, gallic acid, trolox, butylhydroxyanisole, butylhydroxytoluene and 2,6 diisopropylphenol) in associating and non-associating solvents. A significant influence of temperature on the DPPH(*)/antioxidant reaction kinetic is observed for strongly associating solvents (e.g. methanol). This trend is less marked for non-associating solvents (e.g. dioxane, ethyl acetate). The performed experiments prove that the change of solvent structure, caused by temperature increase, influences the estimation of antioxidant properties of phenolic compounds much more than the increase of kinetic energy of reacting molecules and/or the increase of the dissociation degree of hydroxyl groups occurring in antioxidants. PMID- 26139921 TI - In vitro hypoglycemic effects and starch digestibility characteristics of wheat based composite functional flour for diabetics. AB - The associations between chronic feeding of high level of soluble/insoluble fibers and low serum glucose levels have been well documented. In the present study, composite flours were formulated using psyllium, barley and oat at two different levels [WPOB-I = wheat flour (75 %), psyllium (5 %), oat (10 %) and barley (10 %), WPOB-II = wheat flour (60 %), psyllium (10 %), oat (15 %) and barley (15 %)]. Chapaties were prepared from all formulations and various starch fractions were analyzed using controlled enzymatic digestion. The digestibility characteristics were studied using amylolysis kinetics employing porcine pancreatic alpha-amylase in vitro. Results showed that both the variations (WPOB I & WPOB-II) had acceptable sensory qualities and had significantly lower (p <= 0.05) values for total starch (TS), rapidly digestible starch (RDS), resistant starch (RS), starch digestibility index (SDI) and rapidly available glucose (RAG) compared to control. Between the two variations, WPOB-I showed better starch digestibility characteristics with significantly lower (p <= 0.05) starch digestibility index (SDI). In case of amylolysis kinetics, both the variations significantly (p <= 0.05) inhibited alpha-amylase as reflected by lower glucose diffusion and significantly higher (p <= 0.05) glucose dialysis retardation index (GDRI) compared to control. It is inferred that, consumption of the composite flours might be helpful in establishing stable blood glucose pattern due to the redistribution of nutritionally important starch fractions and inhibition of carbohydrate digestion in the gastrointestinal tract. PMID- 26139922 TI - Comparative inhibitory potential of selected dietary bioactive polyphenols, phytosterols on CYP3A4 and CYP2D6 with fluorometric high-throughput screening. AB - Cytochrome P450 (CYP450) inhibition by the bioactive molecules of dietary supplements or herbal products leading to greater potential for toxicity of co administered drugs. The present study was aimed to compare the inhibitory potential of selected common dietary bioactive molecules (Gallic acid, Ellagic acid, beta-Sitosterol, Stigmasterol, Quercetin and Rutin) on CYP3A4 and CYP2D6 to assess safety through its inhibitory potency and to predict interaction potential with co-administered drugs. CYP450-CO complex assay was carried out for all the selected dietary bioactive molecules in isolated rat microsomes. CYP450 concentration of the rat liver microsome was found to be 0.474 nmol/mg protein, quercetin in DMSO has shown maximum inhibition on CYP450 (51.02 +/- 1.24 %) but less when compared with positive control (79.02 +/- 1.61 %). In high throughput fluorometric assay, IC50 value of quercetin (49.08 +/- 1.02-54.36 +/- 0.85 MUg/ml) and gallic acid (78.46 +/- 1.32-83.84 +/- 1.06 MUg/ml) was lower than other bioactive compounds on CYP3A4 and CYP2D6 respectively but it was higher than positive controls (06.28 +/- 1.76-07.74 +/- 1.32 MUg/ml). In comparison of in vitro inhibitory potential on CYP3A4 and CYP2D6, consumption of food or herbal or dietary supplements containing quercetin and gallic acid without any limitation should be carefully considered when narrow therapeutic drugs are administered together. PMID- 26139923 TI - Nootropic and anti-stress effects of rice bran oil in male rats. AB - Rice bran oil (RBO) is an important product of rice bran. It is considered to be one of the most important nutritious oil due to its favorable fatty acid composition and unique composition of naturally occurring biologically active antioxidant compounds. This study was designed to monitor the effects of oral intake of RBO on stress response in rats. RBO was extracted using hexane. Rats were divided into Control and test (RBO-treated). RBO-treated rats were given 0.2 ml/day RBO for 6 weeks. Food intake and body weight changes were monitored weekly. After 6 weeks open field activity and Morris Water Maze (MWM) test were performed. Results showed that weekly cumulative food intake but not body weight were lower in RBO-treated rats during 1st to 5th week of treatment, which were normalized at the end of treatment. Exploratory activity of RBO-treated rats in an open field was increased. Spatial memory in Morris water maze was enhanced in RBO-treated than control rats. An episode of 2 h restraint stress decreased the 24 h food intake of both control and RBO-treated animals. Behavioral deficits were lower in RBO-treated rats. Exposure of 2 h restraint stress increased brain serotonin (5-hydroxytryptamine: 5-HT) metabolism. These increases were lower in RBO-treated restrained than their respective control animals. Serotonergic neurotransmitter mechanism is implicated in stress. The findings of the study show beneficial effects of RBO in learning and memory functions. Moreover, the study also highlights the attenuating effect of RBO on stress induced behavioral and neurochemical effects in rats. PMID- 26139924 TI - Antioxidant property of synbiotic combination of Lactobacillus sp. and wheat bran xylo-oligosaccharides. AB - Wheat bran water unextractable portion (WB-WUP) was subjected to xylanase treatment to obtain a mixture of xylo-oligosaccharides (XOS). XOS mixture was purified on charcoal-celite column and the individual oligosaccharides were separated on a Bio-Gel P-2 column. The sugar composition of the purified oligosaccharides was determined by GLC and their structure was deduced by ESI-MS and (1)H and (13)C NMR. The major oligosaccharides identified were xylobiose and xylotriose (consisting of arabinose). Five strains of lactobacilli (probiotics), XOS (prebiotics) and a combination of both (synbiotics) in milk (as medium) were monitored for antioxidant activity. DPPH radical scavenging activity (~70 %) as well as ferric reducing power (~80 mg/100 ml FeSO4eq) were significantly higher (p < 0.05) in all the synbiotic preparations compared to that of control. The present study indicated that the synbiotic preparations consisting of XOS and lactobacilli can be effectively used as dietary supplement. PMID- 26139925 TI - Extracellular phytase from Aspergillus niger CFR 335: purification and characterization. AB - Phytase, that is extensively used as a feed additive is capable of hydrolyzing phytic acid, an antinutrient found in about 60-80 % of all the plant commodities. This enzyme improves the bioavailability of essential minerals such as Ca(2+), Mg(2+), P, Zn(2+), Fe(3+), that are bound to phytic acid. An extracellular phytase from a local fungal isolate, Aspergillus niger CFR 335 was purified to homogeneity through a three-step column chromatography using DEAE-Sephadex anion exchanger. An active fraction of the enzyme was obtained with NaCl gradient of 2.5 M in DEAE Sephadex column. The enzyme was purified up to 16 fold with a yield of 28.5 %. Substrate specificity studies revealed a highest specific activity of 32.6 +/- 3.1 U/mg for sodium phytate with the Km value of 0.08 +/- 0.1 mM. The molecular weight of the enzyme was 66 kDa with an optimum temperature of 30 degrees C and pH 4.5. Up to 80 % of the activity was retained even after storing the enzyme for 6 months at 4 degrees C. PMID- 26139926 TI - Evaluation of antioxidant interactions in combined extracts of green tea (Camellia sinensis), rosemary (Rosmarinus officinalis) and oak fruit (Quercus branti). AB - Green tea (Camellia sinensis), rosemary (Rosmarinus officinalis) and oak fruit (Quercus branti) are of known medicinal plants used in traditional medicine. They provide substantial antioxidant activities but the possible antioxidant interaction between them has not been studied. In the present study first the bioactive compounds from these three plants were first extracted and thereafter assayed for total phenols, 2, 2-diphenyl-1- picrylhydrazyl (DPPH) radical scavenging activity, total antioxidant capacity (TAOC) and reducing power. In addition, the antioxidant properties of the extracts individually and in combinations were evaluated in soy bean oil as food system. There was a direct relation between total phenolics and antioxidant activities of extracts. Green tea and oak fruit extracts had the highest and least activity, respectively. All three kinds of interactions (synergistic, antagonistic and additive) were observed. In soy bean oil, the only effect was antagonism but even with this effect, combined extract was significantly (P < 0.05) better than butylated hydroxytoluene (BHT) and control sample. Results showed that these three natural extracts and their combination can be effectively used as a substituent of synthetic antioxidant BHT. PMID- 26139927 TI - Effect of shaddock albedo addition on the properties of frankfurters. AB - To explore the potential as a natural auxiliary emulsifier, shaddock albedo was added into frankfurters at six different levels: 0.0, 2.5, 5.0, 7.5, 10 and 12.5 %. The emulsion capacity (EC) of meat batters and cooking properties of frankfurters were evaluated. EC of meat batters was improved with the addition of shaddock albedo and the maximum value was reached at the 5 % albedo concentration. The addition of shaddock albedo resulted in lower cooking losses of frankfurters, with the lowest value obtained at the 7.5 % level. The presence of shaddock albedo decreased the total expressible fluid (TEF) and the proportion of fat in total expressible fluid (PF) which indicated the emulsion stability of frankfurters and the lowest values both occurred at the concentration of 7.5 %. Shaddock albedo inclusion increased the lightness and yellowness of frankfurters and decreased redness. Texture profile analysis showed increased hardness and decreased chewiness of frankfurters with the addition of shaddock albedo. Consequently, shaddock albedo could be a potential source of auxiliary emulsifier filler for emulsion-type meat products. PMID- 26139928 TI - Synbiotic potential of Doogh supplemented with free and encapsulated Lactobacillus plantarum LS5 and Helianthus tuberosus inulin. AB - The survival and effect of free and encapsulated probiotic Lactobacillus plantarum LS5 on acidity, exopolysaccharide production, phase separation and influence on the sensory attributes of probiotic and synbiotic Doogh (typical Iranian drink based on fermented milk) supplemented with Helianthus tuberosus inulin were studied over 22 days storage. Results showed addition of L.plantarum LS5 (free or encapsulated) increased acid development ( degrees D) in Doogh during storage. In addition, phase separation in Doogh with encapsulated probiotic bacteria was slower compared to Doogh with free probiotic bacteria. More exopolysaccharides were observed in Doogh with encapsulated culture compared to those without encapsulated culture. The results confirmed that there was an increased survival of L.plantarum LS5 due to protection of cells by microencapsulation. Also addition of inulin improved survival of free or encapsulated cells in Doogh during storage, but effect of inulin on acidity, exoploysaccharide content and phase separation of samples containing free or encapsulated cells was not significant (P > 0.05). Moreover, sensory evaluation results indicated addition of free or encapsulated probiotic cells and inulin did not significantly affect appearance and color, acidity, flavor and after taste of the Doogh samples over the storage period. Therefore, probiotic and synbiotic Doogh (supplemented with free or encapsulated L.plantarum LS5 and Helianthus tuberosus inulin) are potentially suitable for using as functional dairy foods. PMID- 26139929 TI - Study on a novel process for the separation of phospholipids, triacylglycerol and cholesterol from egg yolk. AB - A novel process for effective separation of phospholipids, triacylglycerol and cholesterol from fresh egg yolk has been developed and validated in this study. Ethanol was the only organic solvent used in the whole procedure. Following initial separation of protein and total lipids by ethanol, most of solidified triacylglycerol was removed from total lipids by low temperature treatment of ethanol extracts within 10 h. Then, beta-cyclodextrin (beta-CD) was used to remove cholesterol from the remaining ethanol extracts and recycling of beta-CD was also studied to obtain cholesterol and reusable beta-CD powder. The highest cholesterol removal rate of nearly 99 % was obtained at beta-CD: cholesterol molar ratio of 5:1, water addition of 15 g/g beta-CD and reacting temperature of 50 degrees C. Ethanol in residual ethanol extracts was removed for obtaining phospholipids by rotary evaporation. The phospholipids produced in this procedure without cholesterol could be safety used as emulsifiers in food or cosmetic industry. PMID- 26139930 TI - Use of agroindustrial wastes (acai fiber and glycerol) in the preparation of cookies. AB - The aim of this study was to assess the effect of adding industrial byproducts (acai fiber and glycerol) on the physical, physicochemical, and sensory properties of cookies. The statistical analysis showed that only the parameters of water content and water activity are significantly influenced by the amount of acai fiber added and by the fiber's particle size. Through sensory analysis of crispness and the flavor, it was found that the best percentage of acai fiber and the best particle size added to the cookie formulation were 10 % and +28 mesh, respectively. From this result, another sensory analysis was performed to evaluate the effect of glycerol over the texture of the cookies. Acceptance indices for the crispness and flavor above 70 % were observed, indicating the possibility for industrial exploitation. Cookies with added industrial byproducts may be considered a source of fiber, as they contain 6 g/100 g fiber. PMID- 26139931 TI - Electrospun antimicrobial hybrid mats: Innovative packaging material for meat and meat-products. AB - To prevent the development and spread of spoilage/pathogenic microorganisms via meat foodstuffs, antimicrobial nanocomposite packaging can serve as a potential alternative. The objective of this study was to develop a new class of antimicrobial hybrid packaging mat composed of biodegradable polyurethane supplemented with virgin olive oil and zinc oxide via electrospinning. Instead of mixing antimicrobial compounds directly with food, incorporation in packaging materials allows the functional effect at food surfaces where microbial activity is localized. The nanofibers were characterized by SEM, EDX, XRD and TEM. The antibacterial activity was tested against two common foodborne pathogens viz., Staphylococcus aureus and Salmonella typhimurium. The present results indicated that incorporation of olive oil in the polymer affected morphology of PU nanofibers and nanocomposite packaging were able to inhibit growth of pathogens. Thus; as-spun mat can be used as prospective antimicrobial packaging, which potentially reduces contamination of meat/meat-products. Moreover, introduced biodegradable packaging for meat products could serve to replace PVC films and simultaneously help to protect natural environment. PMID- 26139932 TI - Production of a transparent lavender flavour nanocapsule aqueous solution and pyrolysis characteristics of flavour nanocapsule. AB - Flavour plays an important role and has been widely used in many products. Usually, the components of flavour are volatile and the sensory perception can be changed as a result of volatilization, heating, oxidation and chemical interactions. Encapsulation can prevent the loss of volatile aromatic ingredients, provide protection and enhance the stability of the core materials. This work concentrated on production of a transparent lavender flavour nanocapsule aqueous solution. The results showed that a transparent lavender flavour microcapsule aqueous solution can be produced using hydroxypropyl-beta cyclodextrin (HP-beta-CD) as wall material. The combination and interaction of flavour and wall materials were investigated by pyrolysis. Pyrolysis characteristics and kinetic parameters of the flavour nanocapsule were determined. During thermal degradation of blank HP-beta-CD and flavour-HP-beta-CD inclusion complex, three main stages can be distinguished. Due to the vaporization of lavender flavour encapsulated in HP-beta-CD, the thermogravimetric (TG) curve of blank HP-beta-CD shows a leveling-off from room temperature to 269 degrees C, while the TG curve of flavour-HP-beta-CD inclusion complex is downward sloping in this temperature range. The kinetic parameters are helpful in understanding the mechanism of molecular recognition between hosts and guests. PMID- 26139933 TI - Effect of refining on quality and composition of sunflower oil. AB - An experimental oil refining unit has been developed and tested for sunflower oil. Crude pressed sunflower oil obtained from a local oil mill was refined using chemical method by degumming, neutralization, bleaching and dewaxing. The quality and composition of crude and refined oil were analysed compared. Reduction in phosphorous content from 6.15 ppm to 0, FFA content from 1.1 to 0.24 % (oleic acid), peroxide value from 22.5 to 7.9 meq/kg, wax content from 1,420 to 200 ppm and colour absorbance value from 0.149 to 0.079 (in spectrophotometer at 460 nm) were observed from crude to refined oil. It was observed that refining did not have significant effect on fatty acid compositions as found in the percentage peak area in the GC-MS chromatogram. The percentage of unsaturated fatty acid in both the oils were recorded to be about 95 % containing 9-Octadecenoic acid (Oleic acid) and 11,14-Eicosadienoic acid (elongated form of linoleic acid). The research results will be useful to small entrepreneurs and farmers for refining of sunflower oil for better marketability. PMID- 26139934 TI - Effect of different sanitizers against Zygosaccharomyces rouxii. AB - Microbial contamination is a problem in food industry. The effects produced by the metabolic activity of yeasts are diverse. If they are found in high numbers it might affect the organoleptic quality of the product. Zygosaccharomyces is the most frequent contaminant genus in sweetened juices that are not properly processed and stored. The aim of this work was to compare the action of five commercial sanitizers against isolates of Z. rouxii and to determine appropriate concentrations and time of action for the inactivation. Peracetic acid, monochloramine, iodophor and quaternary ammonium compounds were evaluated on different surfaces (stainless steel, plastic and glass) at room temperature for 30 and 60 s. It was possible to achieve a 99.99 of death Efficiency corresponding to 4 log10 of reduction for a contact time of 60 s for 0.5% (v/v) of peracetic acid, monochloramines and 0.5% (w/v) of iodophors, 1% for compound with a base of 8% (v/v) of benzyl chloride and 7.5% (v/v) of glutaraldehyde and 5% for sodium hypochlorite (55 g/L active compound). Stainless steel was successfully sanitized with all the compounds tested, and then it would be the most appropriate for the food industry because this material is also highly resistant to abrasion, to impact and to different chemical treatments. In view of the great variety of sanitizing products, the selection of the best sanitizer will depend on efficiency, safety and cost. PMID- 26139935 TI - Processing of a novel powdered herbal coffee (Pistacia Terebinthus L. Fruits Coffee) and its sensorial properties. AB - In this study, the effects of roasting method, grinding and reduction in oil content on the characteristics of Pistacia terebinthus fruit coffee were investigated. Pistacia terebinthus fruit was roasted by microwave, pan and combined (microwave and convection) methods. The degree of roasting was determined by L*, a*, b* color values. The roasting times were 1,500, 1,900 and 1,620 s for microwave, pan and combined roasting methods, respectively. Cold press was used to reduce the oil content both prior to roasting and after the roasting. The oil content was reduced to around 21.5 % in all roasting methods to approach to that of coffee beans. Powdered Pistacia terebinthus fruit coffee brews were compared with each other and Turkish coffee in terms of aroma, flavor, acidity aftertaste, and overall acceptability. Sensorial analysis results showed that coffee brews prepared by pressing after the roasting process were better than those pressing prior to roasting. PMID- 26139936 TI - Effect of storage temperatures and humidity on proximate composition, peroxide value and iodine value of raw cashew nuts. AB - The equilibrium moisture content (EMC) of raw cashew nuts (RCN) were determined using the standard static gravimetric method at 30 degrees C, 40 degrees C and 50 degrees C for relative humidity (RH) ranging from 43 to 90 %. The proximate composition analysis, peroxide value and iodine value of RCN were assessed at this equilibrium stage. The RCN kept under the humidity of 86 and 90 percentage at all studied temperatures developed mold growth within 24-48 h of time. The better storage condition assessed for raw cashew nut is 67 % of RH at 30 degrees C and the values obtained for EMC, proximate composition analysis, peroxide value and iodine value are within the same range as observed with harvested RCN. Highlights * Raw cashew nut storage condition identified * It was analysed with different temperature (30 ( degrees )C, 40 ( degrees )C and 50 ( degrees )C) and relative humidity (43 %-90 %) * Better storage condition for raw cashew nut is in 67 % of RH at 30 ( degrees )C * In this condition the EMC was 8.11 % as within the range of moisture in harvested RCN. PMID- 26139937 TI - The effect of thermal processing on protein quality and free amino acid profile of Terminalia catappa (Indian Almond) seed. AB - The study examined the effect of various processing methods- boiling, drying and roasting- on the in vitro and in vivo protein digestibility and free amino acid profiles of Terminalia catappa seed. Moisture and crude protein of the various samples were determined. In vitro protein digestibility was determined after pepsin digestion. For the in vivo experiment, defatted T. catappa based diet was fed to 3 weeks old Wistar rats for 4 weeks and compared with animals maintained on casein based and nitrogen- free diets. The biological value (BV), net protein utilisation (NPU) and protein efficiency ratio (PER) of the diets were determined. Free amino acid composition was carried out using thin layer chromatography. Moisture was highest in the boiled T. catappa seed (8.30 +/- 0.00 %). The raw, roasted and dried seeds had 5.55 +/- 0.07, 3.88 +/- 0.22 and 3.75 +/ 0.07 % respectively. Crude protein was 19.19, 18.89, 17.62 and 16.36 % in the dried, roasted, boiled and raw seeds respectively. Roasted T. catappa seed had the highest in vitro protein digestibility with 37.52 %, while the dried, boiled and raw samples had digestibility values of 27.57, 27.07 and 24.45 % respectively. All nine essential amino acids were present in T. catappa in high concentrations except methionine and tryptophan. Glutamate was present in the highest concentration. Also, free amino acids were higher in the processed seeds compared to the raw seed. Animals fed T. catappa diet compared favourably with the casein group, thus indicating that the protein is of good quality. PMID- 26139938 TI - Application of a molecular beacon based real-time isothermal amplification (MBRTIA) technology for simultaneous detection of Bacillus cereus and Staphylococcus aureus. AB - A multiplex real-time isothermal amplification assay was developed using molecular beacons for the detection of Bacillus cereus and Staphylococcus aureus by targeting four important virulence genes. A correlation between targeting highly accessible DNA sequences and isothermal amplification based molecular beacon efficiency and sensitivity was demonstrated using phi(Phi)29 DNA polymerase at a constant isothermal temperature of 30 degrees C. It was very selective and consistently detected down to 10(1) copies of DNA. The specificity and sensitivity of this assay, when tested with pure culture were high, surpassing those of currently used PCR assays for the detection of these organisms. The molecular beacon based real-time isothermal amplification (MBRTIA) assay could be carried out entirely in 96 well plates or well strips, enabling a rapid and high-throughput detection of food borne pathogens. PMID- 26139939 TI - Response surface methodology (RSM) in evaluation of the vitamin C concentrations in microwave treated milk. AB - During the microwave treatment process of the milk, response surface methodology (RSM) based on three-level three-factorial Box-Behnken design was used. The response vitamin C concentration was studied. The predicted value of model (11.84 MUg/mL) was in excellent accordance with experimental value (11.83 MUg/mL). Milk layer thickness was the most significant factor that affects the measured responses, and the effects of microwave time and microwave power were dependent on milk layer thickness levels. The variables microwave time,milk layer thickness and microwave power have the opposite effect on vitamin C concentration in milk treated by microwave. Synergistic interactions between milk layer thickness and microwave power was highly significant (p < 0.0001). PMID- 26139940 TI - Green tea yogurt: major phenolic compounds and microbial growth. AB - The purpose of this study was to evaluate fermentation of milk in the presence of green tea (Camellia sinensis) with respect to changes in antioxidant activity, phenolic compounds and the growth of lactic acid bacteria. Pasteurized full fat cow's milk and starter culture were incubated at 41 degrees C in the presence of two different types of green tea extracts. The yogurts formed were refrigerated (4 degrees C) for further analysis. The total phenolic content was highest (p < 0.05) in air-dried green tea-yogurt (MGT) followed by steam-treated green tea (JGT) and plain yogurts. Four major compounds in MGTY and JGTY were detected. The highest concentration of major phenolic compounds in both samples was related to quercetin-rhamnosylgalactoside and quercetin-3-O-galactosyl-rhamnosyl-glucoside for MGTY and JGTY respectively during first 7 day of storage. Diphenyl picrylhydrazyl and ferric reducing antioxidant power methods showed highest antioxidant capacity in MGTY, JGTY and PY. Streptococcus thermophillus and Lactobacillus spp. were highest in MGTY followed by JGTY and PY. This paper evaluates the implementation of green tea yogurt as a new product with functional properties and valuable component to promote the growth of beneficial yogurt bacteria and prevention of oxidative stress by enhancing the antioxidant activity of yogurt. PMID- 26139941 TI - Using the eight-roller mill in the purifier-less mill flow. AB - Double grinding of mill streams without intermediate sieving, i.e. the eight roller milling system provides opportunities for significant reduction of capital cost compared to conventional wheat flour milling system. In this study the effects of using the eight-roller mill in the purifier-less mill flow were investigated. Middlings from the break system of commercial flour mill, which would be sent to the purification system, were intercepted and employed in the experiments. Milling results obtained with double grinding of middlings were compared with the results obtained by conventional system with intermediate sifting before regrinding of stock. At the same roll gap setting and under the same sieving conditions, the eight-roller system produced less flour compared to the conventional system. Results showed that the most efficient way to increase flour yield in the eight-roller milling system is to increase the upper size limit of flour by increasing the sieve aperture. This is not followed by the deterioration of flour quality as determined by ash content. Increase of the upper size limit of flour particles is followed by the decrease of the flour ash content suggesting that it is possible to implement the eight-roller mills in the purifier-less mill flow. PMID- 26139942 TI - Reinforcement Schedule Effects on Long-Term Behavior Change. AB - OBJECTIVE: The primary aim of this study was to determine whether different schedules of contingency management (CM), in conjunction with psychosocial treatment, produced different rates of abstinence and treatment attendance among individuals dependent on methamphetamine. METHODS: Individuals were randomized into 1 of 3 conditions that sought to equate total potential reinforcer magnitude while varying the frequency with which reinforcement was delivered, and comparing these results to those obtained when psychosocial support alone was used. RESULTS: Results indicate that all 3 CM schedules occasioned more abstinent attendance than the group only receiving psychosocial treatment. However, the 3 CM conditions did not differ in any appreciable way. CONCLUSIONS: These results suggest that treatment providers may be able to decrease the frequency of reinforcer delivery in CM paradigms while retaining efficacy to treat psychostimulant use disorders. PMID- 26139943 TI - Conformational effects and stereocontrol in synthesis studies of medium-ring dolabellane carbocycles. AB - Stereoselective reactions are described which lead to functionalization of the dolabellane skeleton. The stereoselectivity is attributed to conformational effects imposed by the eleven-membered ring. An efficient pathway provides for the stereocontrolled synthesis of nonracemic 6(S)-hydroxy-4(E)-dolabellene-3-one 12 and related derivatives. PMID- 26139944 TI - Room Temperature Activation of Aryloxysulfonyl Azides by [Co(II)(TPP)] for Selective Radical Aziridination of Alkenes via Metalloradical Catalysis. AB - Aryloxysulfonyl azides can be effectively activated by commercially available cobalt(II) complex of meso-tetraphenylporphyrin ([Co(TPP)]) at room temperature under neutral and nonoxidative conditions for selective radical aziridination of alkenes via metalloradical catalysis. The [Co(TPP)]-catalyzed radical aziridination system is suitable for different combinations of olefin substrates and aryloxysulfonyl azides, producing various N-aryloxysulfonyl aziridine derivatives in good to excellent yields. In addition to generating the environmentally benign N2 as the only byproduct, this Co(II)-based metalloradical aziridination process features mild reaction conditions and operational simplicity. PMID- 26139945 TI - Preparation and Diels-Alder reactions of 1'-heterosubsituted vinylimidazoles. AB - A Diels-Alder/rearrangement sequence has been pursued in our lab en route to a number of oroidin dimers. In order to access the fully substituted core of these molecules, 1',2'-disubstituted 4-vinylimidazoles were required as dienes. The preparation of a series of a 4-vinylimidazoles containing substituents on the vinyl moiety via hydroalumination/electrophilic trapping or hydrosilylation are described. These derivatives undergo Diels-Alder reactions with N-phenylmaleimide to provide the tetrahydrobenzimidazole derivatives. The cycloadducts derived from halosubstituted systems generally undergo elimination, leading to the corresponding dihydrobenzimidazole, whereas the silyl and stannyl derivatives provide the corresponding 4-substituted tetrahydrobenzimidazole. PMID- 26139946 TI - Stellettapeptins A and B, HIV-inhibitory cyclic depsipeptides from the marine sponge Stelletta sp. AB - Two new HIV-inhibitory depsipeptides, stellettapeptins A (1) and B (2), were isolated from an extract of the marine sponge Stelletta sp., collected from northwestern Australia. Structures of these cyclic nonribosomal peptides were elucidated on the basis of extensive NMR data analysis, and chemical degradation and derivatization studies. Stellettapeptins contain numerous nonproteinogenic amino acid residues and they are the first peptides reported to contain a 3 hydroxy-6,8-dimethylnon-4-(Z)-enoic acid moiety. Compounds 1 and 2 potently inhibit infection of human T-lymphoblastoid cells by HIV-1RF with EC50 values of 23 and 27 nM, respectively. PMID- 26139947 TI - The Effectiveness of Paid Services in Supporting Unpaid Carers' Employment in England. AB - This paper explores the effectiveness of paid services in supporting unpaid carers' employment in England. There is currently a new emphasis in England on 'replacement care', or paid services for the cared-for person, as a means of supporting working carers. The international evidence on the effectiveness of paid services as a means of supporting carers' employment is inconclusive and does not relate specifically to England. The study reported here explores this issue using the 2009/10 Personal Social Services Survey of Adult Carers in England. The study finds a positive association between carers' employment and receipt of paid services by the cared-for person, controlling for covariates. It therefore gives support to the hypothesis that services for the cared-for person are effective in supporting carers' employment. Use of home care and a personal assistant are associated on their own with the employment of both men and women carers, while use of day care and meals-on-wheels are associated specifically with women's employment. Use of short-term breaks are associated with carers' employment when combined with other services. The paper supports the emphasis in English social policy on paid services as a means of supporting working carers, but questions the use of the term 'replacement care' and the emphasis on 'the market'. PMID- 26139948 TI - Are We All Agreed? Consensual Methods and the 'Necessities of Life' in the UK Today. AB - In recent decades, consensual approaches to poverty measurement have been widely adopted in large-scale survey research both in the UK and internationally. However, while ascertaining the extent of public agreement on the 'necessities of life' has been central to this approach, long-standing critiques have questioned the nature of public consensus on poverty derived using survey methods. By drawing on new primary research preparatory to the 2012 UK Poverty and Social Exclusion Survey, we consider the contribution of qualitative methods in understanding public views on necessities and discuss their implications for survey-based poverty measurement. Our findings raise some important conceptual and measurement issues for consensual poverty measures within large-scale social surveys. Firstly, our research suggests that public understandings of the term 'necessity' are diverse and may not always be consistent with researchers' interpretations or with wider usage of this term within consensual poverty measurement. Secondly, a better understanding of the considerations which inform survey respondents' deliberations is needed. Thirdly, our findings have important implications for how we should interpret the concept of 'consensus' within the context of consensual poverty surveys, and emphasise the need for the application of more deliberative methods in determining public views on the 'necessities of life'. PMID- 26139949 TI - Approximate testing in two-stage nonlinear mixed models. AB - We investigate here small sample properties of approximate F-tests about fixed effects parameters in nonlinear mixed models. For estimation of population fixed effects parameters as well as variance components, we apply the two-stage approach. This method is useful and popular when the number of observations per sampling unit is large enough. The approximate F-test is constructed based on large sample approximation to the distribution of nonlinear least squares estimates of subject-specific parameters. We recommend a modified test statistic that takes into consideration approximation to the large sample Fisher information matrix (See [1]). Our main focus is on comparing finite sample properties of broadly used approximate tests (Wald test and likelihood ratio test) and the modified F-test under the null hypothesis, especially accuracy of p values (See [2]). For that purpose two extensive simulation studies are conducted based on pharmacokinetic models (See [3, 4]). PMID- 26139950 TI - A Hierarchical Model for Quantifying Forest Variables Over Large Heterogeneous Landscapes With Uncertain Forest Areas. AB - We are interested in predicting one or more continuous forest variables (e.g., biomass, volume, age) at a fine resolution (e.g., pixel level) across a specified domain. Given a definition of forest/nonforest, this prediction is typically a two-step process. The first step predicts which locations are forested. The second step predicts the value of the variable for only those forested locations. Rarely is the forest/nonforest status predicted without error. However, the uncertainty in this prediction is typically not propagated through to the subsequent prediction of the forest variable of interest. Failure to acknowledge this error can result in biased estimates of forest variable totals within a domain. In response to this problem, we offer a modeling framework that will allow propagation of this uncertainty. Here we envision two latent processes generating the data. The first is a continuous spatial process while the second is a binary spatial process. The continuous spatial process controls the spatial association structure of the forest variable of interest, while the binary process indicates presence of a possible nonzero value for the forest variable at a given location. The proposed models are applied to georeferenced National Forest Inventory (NFI) data and spatially coinciding remotely sensed predictor variables. Due to the large number of observed locations in this dataset we seek dimension reduction not just in the likelihood, but also for unobserved stochastic processes. We demonstrate how a low-rank predictive process can be adapted to our setting and reduce the dimensionality of the data and ease the computational burden. PMID- 26139951 TI - Estimating the lifetime risk of dementia in the Canadian elderly population using cross-sectional cohort survival data. AB - Dementia is one of the world's major public health challenges. The lifetime risk of dementia is the proportion of individuals who ever develop dementia during their lifetime. Despite its importance to epidemiologists and policy-makers, this measure does not seem to have been estimated in the Canadian population. Data from a birth cohort study of dementia are not available. Instead, we must rely on data from the Canadian Study of Heath and Aging, a large cross-sectional study of dementia with follow-up for survival. These data present challenges because they include substantial loss to follow-up and are not representatively drawn from the target population because of structural sampling biases. A first bias is imparted by the cross-sectional sampling scheme, while a second bias is a result of stratified sampling. Estimation of the lifetime risk and related quantities in the presence of these biases has not been previously addressed in the literature. We develop and study nonparametric estimators of the lifetime risk, the remaining lifetime risk and cumulative risk at specific ages, accounting for these complexities. In particular, we reveal the fact that estimation of the lifetime risk is invariant to stratification by current age at sampling. We present simulation results validating our methodology, and provide novel facts about the epidemiology of dementia in Canada using data from the Canadian Study of Health and Aging. PMID- 26139952 TI - Regulatory Anatomy: How "Safety Logics" Structure European Transplant Medicine. AB - This article proposes the term "safety logics" to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, legal documents, technological devices, organizational structures, and work practices aimed at minimizing risk. I use this term to reorient the analytical attention with respect to safety regulation. Instead of evaluating whether safety is achieved, the point is to explore the types of "safety" produced through these logics as well as to consider the sometimes unintended consequences of such safety work. In fact, the EU rules have been giving rise to complaints from practitioners finding the directives problematic and inadequate. In this article, I explore the problems practitioners face and why they arise. In short, I expose the regulatory anatomy of the policy landscape. PMID- 26139953 TI - Region Templates: Data Representation and Management for High-Throughput Image Analysis. AB - We introduce a region template abstraction and framework for the efficient storage, management and processing of common data types in analysis of large datasets of high resolution images on clusters of hybrid computing nodes. The region template abstraction provides a generic container template for common data structures, such as points, arrays, regions, and object sets, within a spatial and temporal bounding box. It allows for different data management strategies and I/O implementations, while providing a homogeneous, unified interface to applications for data storage and retrieval. A region template application is represented as a hierarchical dataflow in which each computing stage may be represented as another dataflow of finer-grain tasks. The execution of the application is coordinated by a runtime system that implements optimizations for hybrid machines, including performance-aware scheduling for maximizing the utilization of computing devices and techniques to reduce the impact of data transfers between CPUs and GPUs. An experimental evaluation on a state-of-the-art hybrid cluster using a microscopy imaging application shows that the abstraction adds negligible overhead (about 3%) and achieves good scalability and high data transfer rates. Optimizations in a high speed disk based storage implementation of the abstraction to support asynchronous data transfers and computation result in an application performance gain of about 1.13*. Finally, a processing rate of 11,730 4K*4K tiles per minute was achieved for the microscopy imaging application on a cluster with 100 nodes (300 GPUs and 1,200 CPU cores). This computation rate enables studies with very large datasets. PMID- 26139954 TI - The neural substrates of complex argument structure representations: Processing 'alternating transitivity' verbs. AB - This study examines the neural correlates of processing verbal entries with multiple argument structures using fMRI. We compared brain activation in response to 'alternating transitivity' verbs, corresponding to two different verbal alternates - one transitive and one intransitive - and simple verbs, with only one, intransitive, thematic grid. Fourteen young healthy participants performed a lexical decision task with the two verb types. Results showed significantly greater activation in the angular and supramarginal gyri (BAs 39 and 40) extending to the posterior superior and middle temporal gyri bilaterally, for alternating compared to simple verbs. Additional activation was detected in bilateral middle and superior frontal gyri (BAs 8 and 9). The opposite contrast, simple compared to alternating verbs, showed no significant differential activation in any regions of the brain. These findings are consistent with previous studies implicating a posterior network including the superior temporal, supramarginal and angular gyri for processing verbs with multiple thematic roles, as well as with those suggesting involvement of the middle and superior frontal gyri in lexical ambiguity processing. However, because 'alternating transitivity' verbs differ from simple intransitives with regard to both the number of thematic grids (two vs. one) and the number of thematic roles (two vs. one), our findings do not distinguish between activations associated with these two differences. PMID- 26139955 TI - Depression Prevention for Early Adolescent Girls: A Pilot Study of All Girls Versus Co-Ed Groups. AB - Given the dramatic increase in depression that occurs during early adolescence in girls, interventions must address the needs of girls. The authors examined whether a depression prevention program, the Penn Resiliency Program, was more effective for girls in all-girls groups than in co-ed groups. Within co-ed groups, the authors also tested whether there were greater effects for boys than for girls. Participants were 208 11- to 14-year-olds. Girls were randomly assigned to all-girls groups, co-ed groups, or control. Boys were assigned to co ed groups or control. Students completed questionnaires on depressive symptoms, hopelessness, and explanatory style before and after the intervention. Girls groups were better than co-ed groups in reducing girls'hopelessness and for session attendance rates but were similar to co-ed groups in reducing depressive symptoms. Co-ed groups decreased depressive symptoms, but this did not differ by gender. Findings support prevention programs and suggest additional benefits of girls groups. PMID- 26139956 TI - Light Dosimetry at Tissue Surfaces for Oblique Incident Circular Fields. AB - Oblique incident light fields are sometimes unavoidable for photodynamic therapy of skin cancers, e.g., for large fields on uneven surface. We have performed Monte-Carlo simulation for circular fields (R = 0.25, 0.35, 0.5, 1, 2, 3, and 8 cm) for reduced scattering coefficient MUs' = 10 cm-1 and attenuation coefficient MUa = 0.1 - 1.0 cm-1. We used anisotropy g = 0.9 and the index of refraction n = 1.4 for all Monte-Carlo simulations. Compared to a broad beam of normal incidence, the peak fluence rate along the central-axis for a slanted beam is increased for otherwise the same geometrical conditions and optical properties. The effective attenuation coefficient is slightly decreased for a slanted beam compared to a normal incident beam. The beam profile for a slanted beam at a fixed depth is no longer symmetrical but is higher towards the lateral side of beam incidence. Since the broad beam with finite radius R can be considered as a convolution of a pencil beam, solution for a slanted pencil beam can be used to determine the light fluence distribution for circular beams with oblique beam incidence. An analytical solution can be obtained for the pencil beam obliquely incident on a semi-infinite medium. The solution can be approximated using the diffusion or P3 theory with one point source or two point sources located at appropriate depths with appropriate weights along the beam pathlength inside the phantom, with corresponding image sources to fulfill the extended boundary condition. The analytical solution agrees well with Monte-Carlo Simulation at depths z > 2costheta t /MU' t , thetat is the incident angle after refraction at the interface. Measurements using an isotropic detector were made in a liquid phantom composed of intralipid and ink to verify the Monte-Carlo simulation results. PMID- 26139957 TI - Dispersion Modeling of Traffic-Related Air Pollutant Exposures and Health Effects Among Children with Asthma in Detroit, Michigan. AB - Vehicular traffic is a major source of ambient air pollution in urban areas. Traffic-related air pollutants, including carbon monoxide, nitrogen oxides, particulate matter less than 2.5 MUm in diameter, and diesel exhaust emissions, have been associated with adverse human health effects, especially in areas near major roads. In addition to emissions from vehicles, ambient concentrations of air pollutants include contributions from stationary sources and background (or regional) sources. Although dispersion models have been widely used to evaluate air quality strategies and policies and can represent the spatial and temporal variation in environments near roads, the use of these models in health studies to estimate air pollutant exposures has been relatively limited. This paper summarizes the modeling system used to estimate exposures in the Near-Roadway Exposure and Urban Air Pollutant Study, an epidemiological study that examined 139 children with asthma or symptoms consistent with asthma, most of whom lived near major roads in Detroit, Michigan. Air pollutant concentrations were estimated with a hybrid modeling framework that included detailed inventories of mobile and stationary sources on local and regional scales; the RLINE, AERMOD, and CMAQ dispersion models; and monitored observations of pollutant concentrations. The temporal and spatial variability in emissions and exposures over the 2.5-year study period and at more than 300 home and school locations was characterized. The paper highlights issues with the development and understanding of the significance of traffic-related exposures through the use of dispersion models in urban-scale exposure assessments and epidemiology studies. PMID- 26139958 TI - Further study of the intrinsic safety of internally shorted lithium and lithium ion cells within methane-air. AB - National Institute for Occupational Safety and Health (NIOSH) researchers continue to study the potential for lithium and lithium-ion battery thermal runaway from an internal short circuit in equipment for use in underground coal mines. Researchers conducted cell crush tests using a plastic wedge within a 20-L explosion-containment chamber filled with 6.5% CH4-air to simulate the mining hazard. The present work extends earlier findings to include a study of LiFePO4 cells crushed while under charge, prismatic form factor LiCoO2 cells, primary spiral-wound constructed LiMnO2 cells, and crush speed influence on thermal runaway susceptibility. The plastic wedge crush was a more severe test than the flat plate crush with a prismatic format cell. Test results indicate that prismatic Saft MP 174565 LiCoO2 and primary spiral-wound Saft FRIWO M52EX LiMnO2 cells pose a CH4-air ignition hazard from internal short circuit. Under specified test conditions, A123 systems ANR26650M1A LiFePO4 cylindrical cells produced no chamber ignitions while under a charge of up to 5 A. Common spiral-wound cell separators are too thin to meet intrinsic safety standards provisions for distance through solid insulation, suggesting that a hard internal short circuit within these cells should be considered for intrinsic safety evaluation purposes, even as a non-countable fault. Observed flames from a LiMnO2 spiral-wound cell after a chamber ignition within an inert atmosphere indicate a sustained exothermic reaction within the cell. The influence of crush speed on ignitions under specified test conditions was not statistically significant. PMID- 26139959 TI - Scalable estimation strategies based on stochastic approximations: Classical results and new insights. AB - Estimation with large amounts of data can be facilitated by stochastic gradient methods, in which model parameters are updated sequentially using small batches of data at each step. Here, we review early work and modern results that illustrate the statistical properties of these methods, including convergence rates, stability, and asymptotic bias and variance. We then overview modern applications where these methods are useful, ranging from an online version of the EM algorithm to deep learning. In light of these results, we argue that stochastic gradient methods are poised to become benchmark principled estimation procedures for large data sets, especially those in the family of stable proximal methods, such as implicit stochastic gradient descent. PMID- 26139960 TI - Ten Commandments of Safe and Optimum Neck Dissections for Cancer. PMID- 26139961 TI - Management of Bile Duct Injury at Various Stages of Presentation: Experience from a Tertiary Care Centre. AB - The clinical presentation, management and outcome of all patients with bile duct injury who presented to our tertiary care centre at various stages after cholecystectomy were analyzed. The patients were categorized into three groups: group A-patients in whom the injury was detected during cholecystectomy, group B patients who presented within 2 weeks of cholecystectomy and group C-patients who presented after 2 weeks of cholecystectomy. Our team acted as rescue surgeons and performed 'on-table' repair for injuries occurring in another unit or in another hospital. Strasberg classification of bile duct injury was followed. In group A, partial and complete transections were managed by repair over T-tube and high hepaticojejunostomy, respectively. Patients in group B underwent endoscopic retrograde cholangiogram and/or magnetic resonance cholangiogram to evaluate the biliary tree. Those with intact common bile duct underwent endoscopic papillotomy and stenting in addition to drainage of intra-abdominal collection when present. For those with complete transection, early repair was considered if there was no sepsis. In presence of intra-abdominal sepsis an attempt was made to create controlled external biliary fistula. This was followed by hepatico jejunostomy at least after 3 months. Group C patients underwent hepaticojejunostomy at least 6 weeks after the injury. The outcome was graded into three categories: grade A-no clinical symptoms, normal LFT; grade B-no clinical symptoms, mild derangement of LFT or occasional episodes of pain or fever; grade C-pain, cholangitis and abnormal LFT; grade D-surgical revision or dilatation required. Fifty nine patients were included in the study and the distribution was group A-six patients, group B-33 patients and group C-20 patients. In group A, one patient with complete transection of the right hepatic duct (type C) and partial injury to left hepatic duct (LHD) underwent right hepaticojejunostomy and repair of the LHD over stent. Two patients with type D and three patients with type E 2 injury underwent repair over T-tube and hepaticojejunostomy, respectively. In group B, all except one of the 18 patients with type A injury underwent endoscopic papillotomy and stenting. The bile leak subsided at a mean interval of 8 days in all, except one patient who died of fulminant sepsis. Of the 15 patients with type E injury, five underwent hepaticojejunostomy after a minimum gap of 3 months. Early repair was considered in 10 patients. Twenty patients in group C underwent hepaticojejunostomy. In a mean follow-up of 40 months, the outcome was grade A in 54 patients, grade B in three patients (one from each of the three groups) and grade D in one patient (group C). The latter patient with a type E3 injury developed recurrent stricture and cholangitis necessitating percutaneous transhepatic dilatation. The high success rate of bile duct repair in the present study can be attributed to the appropriate timing, meticulous technique and the tertiary care experience. PMID- 26139962 TI - Prompt Repair of Post Cholecystectomy Bile Duct Transection Recognized Intraoperatively and Referred Early: Experience from a Tertiary Care Teaching Unit. AB - Postcholecystectomy bile duct injuries are a cause of significant morbidity and occasional mortality. Intraoperative recognition and repair of complete biliary transection with hepaticojejunostomy is the recommended treatment; however, it is possible only in few patients as either the injury is not recognized intraoperatively or the center is not geared up to perform an urgent hepaticojejunostomy in these patients with a nondilated duct. Retrospective analysis of data from a tertiary care referral center over a period of 10 years from January 2000 to December 2009 to report the feasibility and outcomes of prompt repair was done (defined as repair within 72 h of index operation) of postcholecystectomy bile duct injury. Ten patients of postcholecystectomy bile duct injury detected intraoperatively and referred early underwent prompt repair. All patients had a complete transection of the bile duct (type of injuries as per Strasberg classification: Type E V: 1, Type E III: 5, Type E II: 3 and Type E I: 1). The mean duration between injury and bile duct repair in the form of Roux-en Y hepaticojejunostomy (RYHJ) was 22.7 (range 5-42) hours. The mean diameter of the anastomosis was 1.63 (range1-2.1) cm, and the anastomosis was stented in 7 patients. The mean duration of surgery was 4.6 +1.7 h. One patient developed bile leak on the first postoperative day, which settled by day 5. The mean duration of hospital stay was 5.1 (range 4-8) days. With a mean follow-up of 42 (range 24 110) months, all patients had excellent (70 %) or good outcome (30 %). Prompt RYHJ (within first 72 h) for postcholecystectomy biliary transection is an effective treatment and potentially limits the morbidity to the patient. PMID- 26139963 TI - Multi detector CT Imaging of Abdominal and Diaphragmatic Hernias: Pictorial Essay. AB - Diagnosis of abdominal wall hernia is often a clinical problem, especially in occult or in obese patients. Multidetector CT is an accurate method of detecting various types of abdominal and diaphragmatic hernias. It clearly demonstrates the anatomical sites of hernial sac, its contents and possible complications. PMID- 26139964 TI - A Cadaveric Study about the Anomolous Origin of Testicular Arteries Arising from the Accessory Renal Arteries. AB - Testicular arteries are paired vessels, arising from the abdominal aorta, at the level of second lumbar vertebra. Variations in the origin of these vessels highlight a potential importance regarding the vascular supply to the gonads and kidneys. This study was designed to assess the variations in the origin, course, and distance about the point of origin of the testicular arteries. The posterior abdominal walls of 40 male cadavers were studied on either side, during routine dissection in the Department of Anatomy, Kasturba Medical College, Manipal. A majority had a normal course and the variations were reported as: a) Bilateral origin of gonadal arteries from accessory renal arteries, b) Unilateral origin of the gonadal artery from the left accessory renal artery, and c) Unique origin of the right testicular artery from the right inferior epigastric artery and left testicular artery from descending thoracic aorta above the aortic opening of the diaphragm. Due to the embryological attribution, these variations in the testicular arteries indicate an alarming threat to the radiologists and surgeons during renal transplants and nephrectomies, as these vessels monopolize the vascular supply to the gonads. This study was undertaken to document the incidence of testicular arteries originating from accessory renal arteries. PMID- 26139965 TI - Serum Lysozyme (Muramidase) Levels in Intra-Abdominal Abscesses: An Experimental Study. AB - The role of serum lysozyme in the presence of intra-abdominal sepsis was studied to act as an adjunct to various other modalities used for diagnosing intra abdominal abscesses. Lysozyme (muramidase) is a bacteriolytic enzyme located within phagocytic cells including leukocytes. We measured serum concentrations of lysozyme by a standard turbidimetric method on three groups of murine models. One group underwent caecal ligation and puncture (CLP), the second group underwent a sham operation, and the third group was used as controls. In mice with intra abdominal abscesses secondary to caecal ligation and perforation (n = 30), the serum lysozyme levels were increased compared to the sham-operated mice (n = 30) and controls (n = 30) (p = <0.001). In this study, serum lysozyme levels have a high sensitivity and specificity related to the presence of an intra-abdominal abscess in mice. Clinical studies are required to demonstrate its role in humans. PMID- 26139966 TI - A Comparative Study Between Longitudinal Pancreacticojejunostomy v/s Lateral Pancreaticogastrostomy as a Drainage Procedure for Pain Relief in Chronic Pancreatitis Done in a Tertiary Referral Centre of Eastern India. AB - Chronic pancreatitis (CP) is a chronic inflammation of pancreas that leads to progressive fibrosis of pancreatic parenchyma. Commonest indication of surgery in chronic pancreatitis is intractable pain. Choice of procedure depends upon the main pancreatic duct (MPD) morphology. Decompression is useful in dilated and obstructed ducts. Traditional form of decompression is construction of a pancreatico-jejunal anastomosis (LPJ). Another method to achieve ductal decompression is by a pancreaticogastrostomy (LPG) and this study will try to evaluate its effectiveness against pancreaticojejunostomy. To compare the effectiveness of LPG and LPJ in relieving intractable abdominal pain in patients with CP and their respective post-operative complications. This prospective study was done over a period of 4 years from Jan 2007 to Dec 2010 at IPGME & R (SSKM), a tertiary hospital of eastern India. Patients with diagnosis of CP with or without duct calculi and MPD diameter >=7 mm with intractable pain were included. 70 patients were randomly allocated for LPJ and LPG operation by lottery method. Study tools were questionnaires, blood and radiological investigations and standard instruments for open surgery. The patients were prospectively analyzed for duration of surgery and hospital stay, operative/postoperative complications and assessment of postoperative pain relief. Pain relief was assessed as complete (no analgesic requirement), satisfactory (tolerable pain with normal daily activities) and unsatisfactory (hospitalization, narcotics or hampered daily activities). 1. Operative time was shorter in LPG than LPJ (Median 85 vs. 110 min). 2. Incidence of ileus was lesser in LPG group (p = .054). Other complications were comparable in both groups. 3. LPG was associated with shorter duration of hospital stay (Mean 6 vs. 8 days). 4. Pain relief was comparable in LPG and LPJ. LPG is a good alternative to LPJ for CP. PMID- 26139967 TI - Surgical Management of Bile Duct Strictures. AB - Biliary strictures can arise from either benign or malignant diseases. Both are amenable to surgical treatment if the surgeon has a clear understanding of the inciting patho-physiology and appropriate training and skill. This review article focuses on the key aspects of surgical management of biliary strictures. The decision to perform a biliary bypass or radical resection of a biliary stricture depends upon the pathology (benign or malignant) and whether there is curative or palliative intent. Endoscopic findings and brushings can often be non-diagnostic and clinical judgment is required. Final pathology ranges from a delayed stricture years following cholecystectomy to cholangiocarcinoma. Performing the correct operation safely requires clinical experience and knowledge of multiple surgical approaches. Surgical options must maximize cure when possible and relieve biliary obstructive and infectious complications. PMID- 26139968 TI - Hand-Sewn Versus Stapled Esophagogastric Anastomosis in the Neck: A Systematic Review and Meta-analysis of Randomized Controlled Trials. AB - The application of cervical esophagogastric anastomoses was of great concern. However, between circular stapler (CS) and hand-sewn (HS) methods with anastomosis in the neck, which one has better postoperative effects still puzzles surgeons. This study aims to systematically evaluate the effectiveness, security, practicality, and applicability of CS compared with the HS method for the esophagogastric anastomosis after esophageal resection. A systematic literature search, as well as other additional resources, was performed which was completed in January 2013. The relevant randomized controlled trials (RCTs) about the surgical technique for esophageal resection were included. Trial data was reviewed and extracted independently by two reviewers. The quality of the included studies was assessed by the recommended standards basing on Cochrane handbook 5.1.0, and the data was analyzed via RevMan 5 software (version 5.2.0). Nine studies with 870 patients were included. The results showed that in comparing HS to CS methods with cervical anastomosis, no significant differences were found in the risk of developing anastomotic leakages (relative risk (RR) = 1.30, 95 % confidence intervals (CI) 0.87-1.92, p = 0.20), as well as the anastomosis stricture (RR = 0.97, 95 % CI 0.47-1.99, p = 0.93), postoperative mortality (RR = 0.83, 95 % CI 0.43-1.58, p = 0.57), blood loss (mean difference (MD) = 39.68; 95 % CI -6.97, 86.33; p = 0.10) and operative time (MD = 18.05; 95 % CI -3.22, 39.33; p = 0.10). However, the results also illustrated that the CS methods with cervical anastomosis might be less time-consuming and have shorter hospital stay and higher costs. Based upon this meta-analysis, there were no differences in the postoperative outcomes between HS and CS techniques. And the ideal technique of cervical esophagogastric anastomosis following esophagectomy remains under controversy. PMID- 26139969 TI - Ductal Carcinoma In Situ of the Breast. AB - Ductal carcinoma in situ (DCIS) of the breast is a potentially invasive neoplasm. Risk factors include high estrogen states such as use of oral contraceptive (OC) pills, nulliparity, advanced age at first birth, and also family history and genetic mutations. The incidence of this usually clinically silent condition has risen in the past few decades due to widespread screening and diagnostic mammography, with final diagnosis confirmed by biopsy. At present, treatment options include total or simple mastectomy or lumpectomy with radiation. Adjuvant therapy includes antiestrogens like tamoxifen and human epidermal growth factor receptor 2 (HER2) suppression therapy. With the latest advances in chemotherapy and better understanding on the pathogenesis of the lesion, it is anticipated that more effective modalities of treatment may soon be available. PMID- 26139970 TI - De Garengeot's Hernia: a Diagnostic Challenge. AB - Surgical literature defines the case of acute appendicitis in a sac of femoral hernia as de Garengeot's hernia. The diagnosis remains a very hard challenge for surgeon because the symptoms are aspecific and the most effective tools for preoperative evaluation (as abdominal computed tomography and abdominal ultrasound scan) can often be indeterminate or misinterpreted. We report the case of an 85-year-old white male admitted to our unit complaining of a 1-day history of vague abdominal pain, nausea, vomiting, and painful swelling in the right groin. Preoperatively, an incarcerated right femoral hernia was supposed and patient underwent surgery via oblique inguinal incision. The intraoperative finding was a de Garengeot's hernia and an appendectomy with hernia repair was performed. Patient had a regular course and was discharged on the second postoperative day. PMID- 26139971 TI - A Rare Case of Jejunal Diverticulosis Causing Mesenteric Volvulus. AB - Jejunal diverticulosis is a rare asymptomatic entity [1]. In literature, there are only few cases of jejunal diverticulosis where small gut volvulus is reported. The disease entity is important as it may masquerade as hemorrhage, obstruction, or perforation which are life threatening. We report a rare case of small bowel volvulus secondary to jejunal diverticulosis. PMID- 26139972 TI - A rare Case Report of Sigmoid Colon Perforation Due to Accidental Swallowing of Partial Denture. AB - Perforation peritonitis is an important cause of generalized peritonitis and pneumoperitoneum. Large bowel perforation due to swallowed artificial denture is extremely rare. Foreign body can be ingested accidentally or in a suicidal attempt. However, ingested foreign body causing sigmoid colon perforation is extremely rare. Complications caused by ingestion of foreign body in gastrointestinal tract include obstruction, perforation, bleeding, or impaction at the sites of physiological narrowing or acute angulation in gastrointestinal tract. We hereby report a case of sigmoid colon perforation due to swallowed partial denture. PMID- 26139973 TI - Gall bladder Adenocarcinoma in a Young Girl. AB - A 16-year-old girl presented with abdominal discomfort, weakness, and jaundice. General examination revealed deep icterus with hard lymph nodes in left supraclavicular region. On gastrointestinal examination, we appreciated a hard intra-abdominal lump in the right hypochondrium. Biochemical evaluation showed features of obstructive jaundice. Imaging confirmed the presence of gall bladder lump with multiple intra-abdominal lymph nodes. Fine needle aspiration cytology of neck nodes demonstrated metastatic adenocarcinoma. Fine needle aspiration cytology of the gall bladder lump (done under sonographic guidance) confirmed poorly differentiated adenocarcinoma. To the best of our knowledge, malignancy of the gall bladder has not been reported in individuals less than 18 years in India, and only three cases have been reported worldwide in English literature. PMID- 26139974 TI - Giant Omphalocele in an Adolescent Boy. AB - Omphalocele is a congenital abdominal wall defect that permits herniation of abdominal viscera into the umbilical cord. We here report a case of a giant omphalocele in an adolescent boy that has not been reported at this age before. PMID- 26139975 TI - Post-traumatic Jejunojejunal Intussusception. AB - Intussusception is a well-known cause of acute abdomen in the pediatric population. Traumatic intussusception is exceedingly rare, with only 22 cases reported in the English language literature. We report a case of jejunojejunal intussusception that happened after blunt trauma to the abdomen in a 10-year-old boy. The patient presented with clinical presentation of small-bowel obstruction. Through this case and brief review of the literature, we try to focus on the etiology of this rare condition, the clinical particularities, and treatment modalities. PMID- 26139976 TI - Surgical Resection of Phyllodes Tumour: a Radical Approach as a Safeguard Against Local Recurrence. AB - Phyllodes tumour is a rare benign neoplasm of the breast. It is a mixed tumour of epithelial and mesenchymal origin. The epithelial element is characterized by proliferation of ductolobular units. The fibrous tissue and collagen bundles represent the mesenchymal element. It is also known as "cystosarcoma" phyllodes to characterize some important features, viz. cyst-like or cleft-like spaces within the mass along with a leaf- or frond-like pattern of the stromal element. The tumour is well known for its high potential for local recurrence. Most patients in developing countries present with very large breast tumours with close proximity to the skin and pectoralis major. In these cases, there is a need to perform a three-dimensional en bloc removal of the mass with overlying skin and underlying muscle(s). If a skin flap is raised in the vicinity of the tumour, there is a risk of cutting close to the tumour, increasing risk of local recurrence. Here, we describe a surgical technique that permits a three dimensional en bloc removal of phyllodes tumour. PMID- 26139977 TI - Totally Robotic Roux-en-Y Gastric Bypass: Technique. AB - The da Vinci(TM) robotic system (Intuitive Surgical, Inc, Sunnyvale, CA) has been used frequently for urological procedures including radical prostatectomy and pyeloplasty. Its use in bariatric surgery is limited to few high volume centres in the western world. The advantages of robotic assistance are three-dimensional vision, ergonomic advantage and improved precision. We report our experience of using this advanced technology to perform a robotic Roux-en-Y gastric bypass in a 55-year-old obese diabetic patient. We were able to reproduce our standard laparoscopic technique and all the steps of the surgical procedure were done using robotic assistance. PMID- 26139978 TI - P Value <0.05. Is It Always Worth the Chase? PMID- 26139979 TI - The Benefits of Hernioscopy for Type 3 and 4 Amyand's Hernia. PMID- 26139980 TI - Perioperative chemotherapy for resectable gastric cancer: MAGIC and beyond. AB - Over the last 15 years, there have been major advances in the multimodal treatment of gastric cancer, in large part due to several phase III studies showing the treatment benefits of neoadjuvant and adjuvant chemotherapy and chemoradiation protocols. The objective of this editorial is to review the current high-level evidence supporting the use of chemotherapy, chemoradiation and anti-HER2 agents in both the neoadjuvant and adjuvant settings, as well as to provide a clinical framework for use of this data based on our own institutional protocol for gastric cancer. Major studies reviewed include the SWOG/INT 0116, Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC), CLASSIC, ACTS-GC, Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) and Trastuzumab for Gastric Cancer trials. Although these studies have demonstrated that multiple approaches in terms of the timing and therapy for gastric cancer are effective, no standard of care is widely accepted and questions regarding the optimal timing of chemotherapy, the benefit of radiotherapy, the minimum required extent of lymphadenectomy and optimal chemotherapy regimen still exist. Protocols from the upcoming ARTIST II, CRITICS, TOPGEAR, Neo-AEGIS and MAGIC-B studies are outlined, and results from these studies will provide critical information regarding optimal timing and treatment regimen. Additionally, the future directions of gastric cancer research predicated on molecular profiling and tailored therapies based on targetable genetic alterations in individual patient's tumors are addressed. PMID- 26139981 TI - Effector and suppressor T cells in celiac disease. AB - Celiac disease (CD) is a T-cell mediated immune disease in which gliadin-derived peptides activate lamina propria effector CD4+ T cells. This activation leads to the release of cytokines, compatible with a Th1-like pattern, which play a crucial role in the pathogenesis of CD, controlling many aspects of the inflammatory immune response. Recent studies have shown that a novel subset of effector T cells, characterized by expression of high levels of IL-17A, termed Th17 cells, plays a pathogenic role in CD. While these effector T cell subsets produce proinflammatory cytokines, which cause substantial tissue injury in vivo in CD, recent studies have suggested the existence of additional CD4(+) T cell subsets with suppressor functions. These subsets include type 1 regulatory T cells and CD25(+)CD4(+) regulatory T cells, expressing the master transcription factor Foxp3, which have important implications for disease progression. PMID- 26139982 TI - Impact of muscle wasting on survival in patients with liver cirrhosis. AB - Muscle wasting is defined as the progressive and generalized loss of muscle mass. Muscle depletion is a common feature of chronic liver disease found in approximately 40% of patients with cirrhosis. Its etiology is multifactorial subsequent to liver failure and its prevalence increases along with disease severity. Cross-sectional analytic morphometry using computed tomography (CT) scan or magnetic resonance imaging are considered by consensus the gold standards to assess muscle size in cirrhosis for research purposes because they are not biased by fluid accumulation. Several studies have assessed the impact of muscle wasting on overall survival of patients in the waiting list for liver transplantation and there is a general agreement that decreased muscle size assessed by CT scan is an independent predictor for mortality in cirrhosis. It has been proposed that the addition of cross-sectional muscle area into the Model for End-stage Liver Disease can increase its prognostic performance. Nevertheless, the use of CT scan in assessing muscle size is inappropriate for routine clinical practice and an alternative cost-effective, easy to use and accurate tool should be developed. In conclusion, muscle wasting has a detrimental impact on survival of patients with cirrhosis and, thus, it remains to be elucidated if nutritional interventions and exercise could improve muscle wasting and, subsequently, survival in this setting. PMID- 26139983 TI - Immunomodulation of enteric neural function in irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It's generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory function and pain sensitivity associated with IBS. However, partly due to the lack of disease defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. Anecdotally, IBS patients have noted that periods of stress can result in symptom flares and many patients exhibit co morbid stress-related mood disorders such as anxiety and depression. However, in addition to psychosocial stressors, infection-related stress has also been linked with the initiation, persistence and severity of symptom flares. Indeed, prior gastrointestinal infection is one of the strongest predictors of developing IBS. Despite a lack of overt morphological inflammation, the importance of immune factors in the pathophysiology of IBS is gaining acceptance. Subtle changes in the numbers of mucosal immune cell infiltrates and elevated levels of circulating pro-inflammatory cytokines have been reproducibly demonstrated in IBS populations. Moreover, these immune mediators directly affect neural signalling. An exciting new area of research is the role of luminal microbiota in the modulation of neuro-immune signalling, resulting in local changes in gastrointestinal function and alterations in central neural functioning. Progress in this area has begun to unravel some of the complexities of neuroimmune and neuroendocrine interactions and how these molecular exchanges contribute to GI dysfunction. PMID- 26139984 TI - Impaired glucose tolerance in acute pancreatitis. AB - Acute pancreatitis (AP) is an acute inflammatory disease of the exocrine pancreas. In spite of the pivotal role of the endocrine pancreas in glucose metabolism, the impact of impaired glucose tolerance on AP has not been fully elucidated. A meta-analysis of seven observational studies showed that type 2 diabetes mellitus (DM) was associated with an increased risk of AP. The increased risk of AP shown in the meta-analysis was independent of hyperlipidemia, alcohol use and gallstones. Anti-diabetic drugs including incretins might increase the risk of AP, but no intervention trials have confirmed this. Although a controversial finding, DM seems to be associated with severe attacks and organ failure in AP. We analyzed the results of a nationwide epidemiological survey of AP in Japan. We studied the impact of pre-existing DM on the clinical course of AP in 1954 cases for which information on DM status was available at the onset of AP. The prevalence of DM in AP patients (12.8%) was higher than that in the general population in Japan (10.5%). AP patients with DM had higher morbidity of cardiovascular and renal failure than those without DM. About 35% of the idiopathic AP patients with DM had renal failure. The mortality of AP patients with DM (4.0%) was higher than that of AP patients without DM (1.7%). If stratified by etiology, idiopathic, but not alcoholic or biliary, AP patients with DM were predisposed to increased mortality (9.7%). In conclusion, impaired glucose tolerance might have an impact on the development and clinical outcome of AP. However, the impact might depend on the cause of hyperglycemia, the condition of DM including severity, duration and treatment, and the characteristics of the AP patients including age, etiology and comorbidity. PMID- 26139985 TI - Hepatitis B virus and microRNAs: Complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases. AB - Chronic infection with the hepatitis B virus (HBV) is the leading risk factor for the development of hepatocellular carcinoma (HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, microRNAs (miRNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of miRNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between miRNAs and HBV replication and HBV associated disease. Multiple findings suggest that some miRNAs, such as miR-122, and miR-125 and miR-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and miRNAs, including how HBV affects cellular miRNAs, how these miRNAs impact HBV replication, and the relationship between HBV-mediated miRNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and miRNAs, and propose potential applications of miRNA-related techniques that could enhance our understanding of the role miRNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes. PMID- 26139986 TI - Applications of human hepatitis B virus preS domain in bio- and nanotechnology. AB - Human hepatitis B virus (HBV) is a member of the family Hepadnaviridae, and causes acute and chronic infections of the liver. The hepatitis B surface antigen (HBsAg) contains the large (L), middle (M), and small (S) surface proteins. The L protein consists of the S protein, preS1, and preS2. In HBsAg, the preS domain (preS1 + preS2) plays a key role in the infection of hepatocytic cells by HBV and has several immunogenic epitopes. Based on these characteristics of preS, several preS-based diagnostic and therapeutic materials and systems have been developed. PreS1-specific monoclonal antibodies (e.g., MA18/7 and KR127) can be used to inhibit HBV infection. A myristoylated preS1 peptide (amino acids 2-48) also inhibits the attachment of HBV to HepaRG cells, primary human hepatocytes, and primary tupaia hepatocytes. Antibodies and antigens related to the components of HBsAg, preS (preS1 + preS2), or preS1 can be available as diagnostic markers of acute and chronic HBV infections. Hepatocyte-targeting delivery systems for therapeutic molecules (drugs, genes, or proteins) are very important for increasing the clinical efficacy of these molecules and in reducing their adverse effects on other organs. The selective delivery of diagnostic molecules to target hepatocytic cells can also improve the efficiency of diagnosis. In addition to the full-length HBV vector, preS (preS1 + preS2), preS1, and preS1-derived fragments can be useful in hepatocyte-specific targeting. In this review, we discuss the literature concerning the applications of the HBV preS domain in bio- and nanotechnology. PMID- 26139987 TI - Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens. AB - Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN free doesn't mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the "old" IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key issues guiding treatment indication in the next future. The sooner we will change our mind with respect to an a priori obstacle for anti-HCV treatment in the elderly, the sooner we will begin to spare many aged HCV patients from avoidable liver-related complications. PMID- 26139988 TI - Liver fibrosis markers of nonalcoholic steatohepatitis. AB - Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH. PMID- 26139989 TI - Inhibition of ileal bile acid transporter: An emerging therapeutic strategy for chronic idiopathic constipation. AB - Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation. PMID- 26139990 TI - Altered distribution of regulatory lymphocytes by oral administration of soy extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance. AB - AIM: To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non alcoholic steatohepatitis (NASH). METHODS: Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers. RESULTS: Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution. CONCLUSION: Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance. PMID- 26139991 TI - Integrin alphavbeta6 sustains and promotes tumor invasive growth in colon cancer progression. AB - AIM: To detect the mechanism by which colon tumor escapes the growth constraints imposed on normal cells by cell crowding and dense pericellular matrices. METHODS: An immunohistochemical study of integrin alphavbeta6 and matrix metalloproteinase-9 (MMP-9) was performed on tissue microarrays of 200 spots, including 100 cases of colon tumors. RESULTS: High immunoreactivity for alphavbeta6 (73.7%; 28/38) and MMP-9 (76.5%; 52/68) was observed in invasive tumor portions. Furthermore, the effects of integrin alphavbeta6 on tumor invasive growth in nude mice were detected. Tumor invasive growth and high expression of both alphavbeta6 and MMP-9 were only seen in tumors resulting from WiDr cells expressing alphavbeta6 in the tumorigenicity assay. Flow cytometry was applied to analyze alphavbeta6 expression in colon cancer WiDr and SW480 cells. The effects of cell density on alphavbeta6 expression and MMP-9 secretion were also detected by Biotrak MMP-9 activity assay and gelatin zymography assay. High cell density evidently enhanced alphavbeta6 expression and promoted MMP-9 secretion compared with low density. CONCLUSION: Integrin alphavbeta6 sustains and promotes tumor invasive growth in tumor progression via a self-perpetuating mechanism. Integrin alphanubeta6-mediated MMP-9 secretion facilitates pericellular matrix degradation at high cell density, which provides the basis of invasive growth. PMID- 26139992 TI - Grape seed proanthocyanidin protects liver against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress. AB - AIM: To explore the effect of grape seed proanthocyanidin (GSP) in liver ischemia/reperfusion (IR) injury and alleviation of endoplasmic reticulum stress. METHODS: Male Sprague-Dawley rats (220-250 g) were divided into three groups, namely, sham, IR, and GSP groups (n = 8 each). A liver IR (70%) model was established and reperfused for 6 h. Prior to reperfusion, the GSP group was administered with GSP (100 mg/kg) for 15 d, and liver histology was then investigated. Serum aminotransferase and inflammatory mediators coupled with superoxide dismutase and methane dicarboxylic aldehyde were detected. Western blot was conducted to analyze the expression of glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-kappab. Apoptotic cells were detected by TUNEL staining. RESULTS: The serum aminotransferase, apoptotic cells, and Suzuki scores decreased in the GSP group compared with the IR group (Ps < 0.05). The methane dicarboxylic aldehyde level was decreased in the GSP group, but the superoxide dismutase level was reversed (Ps < 0.05). Similarly, GSP downregulated the proinflammatory factors and upregulated the levels of anti-inflammatory factors (Ps < 0.05). Western blot data showed that GSP increased glucose-regulated protein 78 expression and suppressed expression of CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-kappab compared with the IR group. CONCLUSION: GSP possesses antioxidative, anti-inflammatory, and antiapoptotic effects by relieving endoplasmic reticulum stress through regulation of related signaling pathways to protect the liver against IR injury. PMID- 26139993 TI - Increased liver markers are associated with higher risk of type 2 diabetes. AB - AIM: To investigate the association between liver markers and the risk of type 2 diabetes (T2DM) and impaired fasting glucose (IFG). METHODS: A total of 8863 participants (3408 men and 5455 women) over 30 years of age were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2011). The associations of serum liver markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT, and gamma-glutamyltransferase (GGT) with T2DM and IFG were analyzed using logistic regression models. Participants were divided into sex-specific quartiles on the basis of liver markers. RESULTS: The prevalence of T2DM and IFG were 11.3% and 18.3%. Increasing quartiles of ALT and GGT were positively and AST/ALT were negatively correlated with T2DM and IFG. Analysis of the liver marker combinations showed that if any two or more markers were in the highest risk quartile, the risks of both T2DM and IFG increased significantly. The risk was greatest when the highest ALT and GGT and lowest AST/ALT quartile were combined, with the risk of T2DM at 3.21 (95%CI: 1.829 5.622, P < 0.001) in men and 4.60 (95%CI: 3.217-6.582, P < 0.001) in women. Men and women with the highest AST and ALT and lowest AST/ALT quartile had a 1.99 and 2.40 times increased risk of IFG. CONCLUSION: Higher levels of GGT and ALT and lower AST/ALT within the physiological range are independent, additive risk factors of T2DM and IFG. PMID- 26139994 TI - Prognostic factors of spontaneously ruptured hepatocellular carcinoma. AB - AIM: To evaluate the prognostic factors in patients with spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: Seventy-nine patients experiencing spontaneous rupture of HCC between April 2004 and August 2014 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using a Cox regression hazard model. RESULTS: Of the 79 patients with HCC rupture, 17 (21.5%) underwent surgery, 32 (40.5%) underwent transarterial embolization (TAE), and 30 (38%) received conservative treatment. The median survival time was 125 d, and the mortality rate at 30 d was 27.8%. Multivariate analysis revealed that lesion length (HR = 1.46, P < 0.001), lesion number (HR = 1.37, P = 0.042), treatment before tumor rupture (HR = 4.36, P = 0.019), alanine transaminase levels (HR = 1.0, P = 0.011), bicarbonate levels (HR = 1.18, P < 0.001), age (HR = 0.96, P = 0.026), anti-tumor therapy during the follow-up period (HR = 0.21, P = 0.008), and albumin levels (HR = 0.89, P = 0.010) were independent prognostic factors of survival after HCC rupture. The Barcelona Clinic Liver Cancer (BCLC) stage was also an important prognostic factor; the median survival times for BCLC stages A, B and C were 251, 175 and 40 d, respectively (P < 0.001). CONCLUSION: Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival. PMID- 26139995 TI - Low yield of routine duodenal biopsies for evaluation of abdominal pain. AB - AIM: To determine the yield of biopsying normal duodenal mucosa for investigation of abdominal pain. METHODS: This is a retrospective chart review of consecutive patients who underwent esophagogastroduodenoscopy (EGD) with duodenal biopsies of normal appearing duodenal mucosa for an indication that included abdominal pain. All the patients in this study were identified from an electronic endoscopy database at a single academic medical center and had an EGD with duodenal biopsies performed over a 4-year period. New diagnoses that were made as a direct result of duodenal biopsies were identified. All duodenal pathology reports and endoscopy records were reviewed for indications to perform the examination as well as the findings; all the medical records were reviewed. Exclusion criteria included age less than 18 years, duodenal mass, nodule, or polyp, endoscopic duodenitis, duodenal scalloping, known celiac disease, positive celiac serology, Crohns disease, or history of bone marrow transplant. Information was collected in a de-identified database with pertinent demographic information including human immunodeficiency virus (HIV) status, and descriptive statistics were performed. RESULTS: About 300 patients underwent EGD with biopsies of benign appearing or normal appearing duodenal mucosa. The mean age of patients was 44.1 +/- 16.8 years; 189 of 300 (63%) were female. A mean of 4.3 duodenal biopsies were performed in each patient. In the subgroup of patients with abdominal pain without anemia, diarrhea, or weight loss the mean age was 43.4 +/- 16.3 years. Duodenal biopsies performed for an indication that included abdominal pain resulting in 4 new diagnoses (3 celiac disease and 1 giardiasis) for an overall yield of 1.3%. 183 patients with abdominal pain without anemia, diarrhea, or weight loss (out of the total 300 patients) underwent duodenal biopsy of duodenal mucosa resulting in three new diagnoses (two cases of celiac disease and one giardiasis) for a yield of 1.6%. Duodenal biopsies of 19 HIV patients presenting for evaluation of abdominal pain did not reveal any new diagnoses. Information pertaining to new diagnoses is provided. CONCLUSION: Routine biopsy of normal appearing duodena in patients with abdominal pain should be reserved for those with a high pre-test probability given its low diagnostic yield. PMID- 26139996 TI - Patient characteristics with high or low blood urea nitrogen in upper gastrointestinal bleeding. AB - AIM: To examine characteristics of patients with blood urea nitrogen (BUN) levels higher and lower than the normal limit. METHODS: Patient records between April 2011 and March 2014 were analyzed retrospectively. During this time, 3296 patients underwent upper endoscopy. In total, 50 male (69.2 +/- 13.2 years) and 26 female (72.3 +/- 10.2 years) patients were assessed. Patients were divided into two groups based on BUN levels: higher than the normal limit (21.0 mg/dL) (H) and lower than the normal limit (L). One-way analysis of variance was performed to reveal differences in the variables between the H and L groups. Fisher's exact test was used to compare the percentage of patients with gastric ulcer or gastric cancer in the H and L groups. RESULTS: White blood cell count was higher in the H group than in the L group (P = 0.0047). Hemoglobin level was lower in the H group than in the L group (P = 0.0307). Glycated hemoglobin was higher in the H group than in the L group (P = 0.0264). The percentage of patients with gastric ulcer was higher in the H group (P = 0.0002). The H group contained no patients with gastric cancer. CONCLUSION: Patients with BUN >= 21 mg/dL might have more severe upper gastrointestinal bleeding. PMID- 26139997 TI - Risk factors of organ failure in cholangitis with bacteriobilia. AB - AIM: To identify the risk factors for organ failure (OF) in cholangitis with bacteriobilia. METHODS: This study included 182 patients with acute cholangitis who underwent percutaneous transhepatic biliary drainage between January 2005 and April 2013. We conducted a retrospective analysis of comprehensive clinical and laboratory data. RESULTS: There were 24 cases (13.2%) of OF and five deaths (2.7%). Bile culture was positive for microbial growth in 130 out of 138 (94.2%) patients. In multivariate analysis of 130 patients with positive bile cultures, significant predictive factors for OF were the presence of extended-spectrum beta lactamase (ESBL) organisms in blood cultures, pre-existing renal dysfunction, and choledocholithiasis as an etiology, with odds ratios of 15.376, 6.319, and 3.573, respectively. We developed a scoring system with a regression coefficient of each significant variable. The OF score was calculated using the following equation: (2.7 * ESBL organisms in blood cultures) + (1.8 * pre-existing renal dysfunction) + (1.3 * choledocholithiasis). This scoring system for predicting OF was highly specific (99.1%) and had a positive predictive value of 86.2%. CONCLUSION: ESBL organisms in blood cultures, pre-existing renal dysfunction, and choledocholithiasis are risk factors for OF in cholangitis with bacteriobilia. The OF scoring system may aid clinicians to identify a poor prognosis group. PMID- 26139998 TI - Lymph node ratio-based staging system for esophageal squamous cell carcinoma. AB - AIM: To analyze a modified staging system utilizing lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Clinical data of 2011 patients with ESCC who underwent surgical resection alone between January 1995 and June 2010 at the Cancer Hospital of Shantou University Medical College were reviewed. The LNR, or node ratio (Nr) was defined as the ratio of metastatic LNs ompared to the total number of resected LNs. Overall survival between groups was compared with the log-rank test. The cutoff point of LNR was established by grouping patients with 10% increment in Nr, and then combining the neighborhood survival curves using the log-rank test. A new TNrM staging system, was constructed by replacing the American Joint Committee on Cancer (AJCC) N categories with the Nr categories in the new TNM staging system. The time dependent receiver operating characteristic curves were used to evaluate the predictive performance of the seventh edition AJCC staging system and the TNrM staging system. RESULTS: The median number of resected LNs was 12 (range: 4-44), and 25% and 75% interquartile rangeswere8 and 16. Patients were classified into four Nr categories with distinctive survival differences (Nr0: LNR = 0; Nr1: 0% < LNR <= 10%; Nr2: 10% < LNR <= 20%; and Nr3: LNR > 20%). From N categories to Nr categories, 557 patients changed their LN stage. The median survival time (MST) for the four Nr categories (Nr0-Nr3) was 155.0 mo, 39.0 mo, 28.0 mo, and 19.0 mo, respectively, and the 5-year overall survival was 61.1%, 41.1%, 33.0%, and 22.9%, respectively (P < 0.001). Overall survival was significantly different for the AJCC N categories when patients were subgrouped into 15 or more vs fewer than 15 examined nodes, except for the N3 category (P = 0.292). However, overall survival was similar when the patients in all four Nr categories were subgrouped into 15 or more vs fewer than 15 nodes. Using the time-dependent receiver operating characteristic, we found that the Nr category and TNrM stage had higher accuracy in predicting survival than the AJCC N category and TNM stage. CONCLUSION: A staging system based on LNR may have better prognostic stratification of patients with ESCC than the current TNM system, especially for those undergoing limited lymphadenectomy. PMID- 26139999 TI - Use of magnetic resonance elastography for assessing liver functional reserve: A clinical study. AB - AIM: To investigate the value of magnetic resonance elastography (MRE) with regard to assessing liver functional reserve. METHODS: Data from inpatients diagnosed with a liver tumor at an interventional radiology department from July 2013 to June 2014 were analyzed. A 3.0 Tesla magnetic resonance unit was used to scan 32 patients with confirmed diagnoses of hepatocellular carcinoma (HCC); an MRE sequence was added to the protocol, and the data were reconstructed and analyzed by two attending radiologists. Regions of interest were identified in different slices of the non-tumor liver parenchyma to measure average stiffness. In addition, the indocyanine green (ICG) test was performed no more than 1 wk before or after the magnetic resonance examination for all 32 patients; the ICG retention rate at 15 min (ICGR-15) and the ICG plasma clearance rate (ICG-K) were recorded. Correlational analyses were performed between the liver stiffness values and the ICGR-15 as well as between the liver stiffness values and the ICG K. RESULTS: Magnetic resonance imaging, including an MRE sequence and the ICG test, was performed successfully in all 32 enrolled patients. None of the patients developed complications. The mean +/- SD of the elasticity values measured by the two attending radiologists were 4.7 +/- 2.2 kPa and 4.7 +/- 2.1 kPa, respectively. The average liver stiffness value of the non-tumor parenchyma measured using MRE in HCC patients was 4.7 +/- 2.2 kPa. The average ICGR-15 was 0.089 +/- 0.077, and the average ICG-K was 0.19 +/- 0.07. We found that the liver stiffness value of the non-tumor parenchyma was significantly and positively related to the ICGR-15 (r = 0.746, P < 0.01) as well as significantly and negatively related to the ICG-K (r = -0.599, P < 0.01). The ICGR-15 was significantly and negatively related to the ICG-K (r = -0.852, P < 0.01). CONCLUSION: MRE is accurate and non-invasive; furthermore, it can be used to effectively assess the liver functional reserve of HCC patients. PMID- 26140000 TI - Liver fat deposition and mitochondrial dysfunction in morbid obesity: An approach combining metabolomics with liver imaging and histology. AB - AIM: To explore the usefulness of magnetic resonance imaging (MRI) and spectroscopy (MRS) for assessment of non-alcoholic fat liver disease (NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesity-induced NAFLD in an observational, prospective, single-site, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described (1)H NMR-based metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from (1)H NMR spectra obtained after surgery were omitted due to technical limitations. RESULTS: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, which excluded the presence of non-alcoholic steatohepatitis (NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the -CH3 peak (0.9 ppm), the -CH2- peak (1.3 ppm, mostly triglyceride) and the CH=CH- peak (2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may help to explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients. CONCLUSION: MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose. PMID- 26140001 TI - Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up. AB - AIM: To assess the evolution of duodenal lymphocytosis (DL), a condition characterized by increased intraepithelial lymphocytes (IELs), over 2 years of follow-up. METHODS: Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease (CD) were included. Evaluation of IELs infiltrate in duodenal biopsy samples was carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: IgG and IgA anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance imaging were performed when necessary. Risk factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR. RESULTS: Eighty five patients (16 males, 69 females, aged 34.1 +/- 12.5 years) were followed up for a mean period of 21.7 +/- 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15 25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti transglutaminase and anti-endomysium, whilst 5 showed IgG anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity (GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn's disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack of diagnostic evidence. At multivariate analysis, the evolution towards CD was associated with an IELs infiltrate > 25 (OR = 1640.4) or 15-25 (OR = 16.95), human leukocyte antigen (HLA) DQ2/8 (OR = 140.85) or DQA1*0501 (OR = 15.36), diarrhea (OR = 5.56) and weakness (OR = 11.57). GS was associated with IELs 15-25 (OR = 28.59), autoimmune thyroiditis (OR = 87.63), folate deficiency (OR = 48.53) and diarrhea (OR = 54.87). CONCLUSION: DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS. PMID- 26140002 TI - Immunohistochemical CD3 staining detects additional patients with celiac disease. AB - AIM: To investigate whether performing immunohistochemical CD3 staining, in order to improve the detection of intra-epithelial lymphocytosis, has an additional value in the histological diagnosis of celiac disease. METHODS: Biopsies obtained from 159 children were stained by hematoxylin and eosin (HE) and evaluated using the Marsh classification. CD3 staining was subsequently evaluated separately and independently. RESULTS: Differences in evaluation between the routine HE sections and CD3 staining were present in 20 (12.6%) cases. In 10 (6.3%) patients the diagnosis of celiac disease (Marsh II and III) changed on examination of CD3 staining: in 9 cases, celiac disease had initially been missed on the HE sections, while 1 patient had been over-diagnosed on the routine sections. In all patients, the final diagnosis based on CD3 staining, was concordant with serological results, which was not found previously. In the other 10 (12.3%) patients, the detection of sole intra-epithelial lymphocytosis (Marsh I) improved. Nine patients were found to have Marsh I on CD3 sections, which had been missed on routine sections. Interestingly, the only patient with negative serology had Giardiasis. Finally, in 1 patient with negative serology, in whom Marsh I was suspected on HE sections, this diagnosis was withdrawn after evaluation of the CD3 sections. CONCLUSION: Staining for CD3 has an additional value in the histological detection of celiac disease lesions, and CD3 staining should be performed when there is a discrepancy between serology and the diagnosis made on HE sections. PMID- 26140003 TI - Esophageal dysphagia and reflux symptoms before and after oral IQoro(R) training. AB - AIM: To examine whether muscle training with an oral IQoro(R) screen (IQS) improves esophageal dysphagia and reflux symptoms. METHODS: A total of 43 adult patients (21 women and 22 men) were consecutively referred to a swallowing center for the treatment and investigation of long-lasting nonstenotic esophageal dysphagia. Hiatal hernia was confirmed by radiologic examination in 21 patients before enrollment in the study (group A; median age 52 years, range: 19-85 years). No hiatal hernia was detected by radiologic examination in the remaining 22 patients (group B; median age 57 years, range: 22-85 years). Before and after training with an oral IQS for 6-8 mo, the patients were evaluated using a symptom questionnaire (esophageal dysphagia and acid chest symptoms; score 0-3), visual analogue scale (ability to swallow food: score 0-100), lip force test (>= 15 N), velopharyngeal closure test (>= 10 s), orofacial motor tests, and an oral sensory test. Another twelve patients (median age 53 years, range: 22-68 years) with hiatal hernia were evaluated using oral IQS traction maneuvers with pressure recordings of the upper esophageal sphincter and hiatus canal as assessed by high resolution manometry. RESULTS: Esophageal dysphagia was present in all 43 patients at entry, and 98% of patients showed improvement after IQS training [mean score (range): 2.5 (1-3) vs 0.9 (0-2), P < 0.001]. Symptoms of reflux were reported before training in 86% of the patients who showed improvement at follow up [1.7 (0-3) vs 0.5 (0-2), P < 0.001). The visual analogue scale scores were classified as pathologic in all 43 patients, and 100% showed improvement after IQS training [71 (30-100) vs 22 (0-50), P < 0.001]. No significant difference in symptom frequency was found between groups A and B before or after IQS training. The lip force test [31 N (12-80 N) vs 54 N (27-116), P < 0.001] and velopharyngeal closure test values [28 s (5-74 s) vs 34 s (13-80 s), P < 0.001] were significantly higher after IQS training. The oral IQS traction results showed an increase in mean pressure in the diaphragmatic hiatus region from 0 mmHg at rest (range: 0-0 mmHG) to 65 mmHg (range: 20-100 mmHg). CONCLUSION: Oral IQS training can relieve/improve esophageal dysphagia and reflux symptoms in adults, likely due to improved hiatal competence. PMID- 26140004 TI - Four-sample lactose hydrogen breath test for diagnosis of lactose malabsorption in irritable bowel syndrome patients with diarrhea. AB - AIM: To validate 4-sample lactose hydrogen breath testing (4SLHBT) compared to standard 13-sample LHBT in the clinical setting. METHODS: Irritable bowel syndrome patients with diarrhea (IBS-D) and healthy volunteers (HVs) were enrolled and received a 10 g, 20 g, or 40 g dose lactose hydrogen breath test (LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h (13 measurements). The detection rates of lactose malabsorption (LM) and lactose intolerance (LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT. RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups (P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT (97%-100%, Kappa 0.815-0.942) with high sensitivity (90%-100%) and specificity (100%) at all three lactose doses in both groups. CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice. PMID- 26140005 TI - Management of duodenal stump fistula after gastrectomy for gastric cancer: Systematic review. AB - AIM: To identify the most effective treatment of duodenal stump fistula (DSF) after gastrectomy for gastric cancer. METHODS: A systematic review of the literature was performed. PubMed, EMBASE, Cochrane Library, CILEA Archive, BMJ Clinical Evidence and UpToDate databases were analyzed. Three hundred eighty eight manuscripts were retrieved and analyzed and thirteen studies published between 1988 and 2014 were finally selected according to the inclusion criteria, for a total of 145 cases of DSF, which represented our group of study. Only patients with DSF after gastrectomy for malignancy were selected. Data about patients' characteristics, type of treatment, short and long-term outcomes were extracted and analyzed. RESULTS: In the 13 studies different types of treatment were proposed: conservative approach, surgical approach, percutaneous approach and endoscopic approach (3 cases). The overall mortality rate was 11.7% for the entire cohort. The more frequent complications were sepsis, abscesses, peritonitis, bleeding, pneumonia and multi-organ failure. Conservative approach was performed in 6 studies for a total of 79 patients, in patients with stable general condition, often associated with percutaneous approach. A complete resolution of the leakage was achieved in 92.3% of these patients, with a healing time ranging from 17 to 71 d. Surgical approach included duodenostomy, duodeno jejunostomy, pancreatoduodenectomy and the use of rectus muscle flap. In-hospital stay of patients who underwent relaparotomy ranged from 1 to 1035 d. The percutaneous approach included drainage of abscesses or duodenostomy (32 cases) and percutaneous biliary diversion (13 cases). The median healing time in this group was 43 d. CONCLUSION: Conservative approach is the treatment of choice, eventually associated with percutaneus drainage. Surgical approach should be reserved for severe cases or when conservative approaches fail. PMID- 26140006 TI - Updated meta-analysis of pancreatic stent placement in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis. AB - AIM: To investigate the efficacy and safety profile of pancreatic duct (PD) stent placement for prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: We performed a search of MEDLINE, EMBASE, and Cochrane Library to identify randomized controlled clinical trials of prophylactic PD stent placement after ERCP. RevMan 5 software provided by Cochrane was used for the heterogeneity and efficacy analyses, and a meta analysis was performed for the data that showed homogeneity. Categorical data are presented as relative risks and 95% confidence intervals (CIs), and measurement data are presented as weighted mean differences and 95%CIs. RESULTS: The incidence rates of severe pancreatitis, operation failure, complications and patient pain severity were analyzed. Data on pancreatitis incidence were reported in 14 of 15 trials. There was no significant heterogeneity between the trials (I(2) = 0%, P = 0.93). In the stent group, 49 of the 1233 patients suffered from PEP, compared to 133 of the 1277 patients in the no-stent group. The results of this meta-analysis indicate that it may be possible to prevent PEP by placing a PD stent. CONCLUSION: PD stent placement can reduce postoperative hyperamylasemia and might be an effective and safe option to prevent PEP if the operation indications are well controlled. PMID- 26140007 TI - Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy: A single center report of 8 cases. AB - This article describes cases of anti-tumor necrosis factor (TNF)-alpha-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis (AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-alpha antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics. PMID- 26140009 TI - Successful biliary drainage using a metal stent through the gastric stoma. AB - We report a case of biliary drainage for malignant stricture using a metal stent with an ultrathin endoscope through the gastric stoma. A 78-year-old female was referred to our hospital for jaundice and fever. She had undergone percutaneous endoscopic gastrostomy (PEG) for esophageal obstruction after radiation therapy for cancer of the pharynx. Abdominal contrast-enhanced computed tomography showed a 3-cm enhanced mass in the middle bile duct and dilatation of the intra-hepatic bile duct. We initially performed endoscopic retrograde cholangiopancreatography (ERCP) with a trans-oral approach. However, neither the side-viewing endoscope nor the ultrathin endoscope passed through the esophageal orifice. Thus, we eventually performed ERCP via the PEG stoma using an ultrathin endoscope. We performed biliary drainage with a 6F introducer self-expanding metal stent. The cytology findings obtained by brush cytology showed malignancy. Her laboratory results were restored to normal levels after drainage and no complication occurred. PMID- 26140008 TI - Enteral metallic stenting by balloon enteroscopy for obstruction of surgically reconstructed intestine. AB - We present three cases of self-expandable metallic stent (SEMS) placement using a balloon enteroscope (BE) and its overtube (OT) for malignant obstruction of surgically reconstructed intestine. A BE is effective for the insertion of an endoscope into the deep bowel. However, SEMS placement is impossible through the working channel, because the working channel of BE is too small and too long for the stent device. Therefore, we used a technique in which the BE is inserted as far as the stenotic area; thereafter, the BE is removed, leaving only the OT, and then the stent is placed by inserting the stent device through the OT. In the present three cases, a modification of this technique resulted in the successful placement of the SEMS for obstruction of surgically reconstructed intestine, and the procedures were performed without serious complications. We consider that the present procedure is extremely effective as a palliative treatment for distal bowel stenosis, such as in the surgically reconstructed intestine. PMID- 26140010 TI - Case of plasmablastic lymphoma of the sigmoid colon and literature review. AB - Plasmablastic lymphoma (PBL) is a rare form of non-Hodgkin's lymphoma that is associated with human immunodeficiency virus (HIV) infection. Although PBL is most commonly observed in the oral cavity of HIV-positive patients, it can also be observed at extra-oral sites in HIV-negative patients. This report represents an unusual case of HIV-negative PBL that occurred in the sigmoid colon. This patient had a history of systemic lupus erythematosus and an underlying immunosuppressive state from long term steroid therapy. The lymphoma cells were positive for CD138, kappa light chain restriction and Epstein-Barr virus and negative for CD20/L26, CD3, CD79a, UCHL1 (CD45RO) and cytokeratin (AE1/AE3). The patient died approximately 2 mo after the operation. In the present paper, we review cases of PBL of the colon in HIV-negative patients. PMID- 26140011 TI - Resection of the main trunk of the superior mesenteric vein without reconstruction during surgery for giant pancreatic mucinous cystadenoma: A case report. AB - Pancreatic tumors, with peri-pancreatic main vascular invasion, especially the superior mesenteric vein (SMV) or the portal vein, are very common. In some cases, vascular resection and reconstruction are required for complete resection of pancreatic tumors. However, the optimum surgical method for venous management is controversial. Resection of the SMV without reconstruction during surgery for pancreatic tumors is rarely reported. Here we present the case of a 58-year-old woman with a giant pancreatic mucinous cystadenoma adhering to the SMV, who underwent an en bloc tumor resection, including the main trunk of the SMV and the spleen. No venous reconstruction was performed during surgery. No ischemic changes occurred in the bowel. The presence of several well-developed collateral vessels was shown by 3-dimensional computed tomography examination. The patient had an uneventful postoperative period and was discharged. This case indicated that the main trunk of the SMV can be resected without venous reconstruction if adequate collateralization has formed. PMID- 26140012 TI - Endoscopic mucosal resection of duodenal bulb adenocarcinoma with neuroendocrine features: An extremely rare case report. AB - Duodenal adenocarcinoma, especially duodenal bulb with neuroendocrine features (NEF), is extremely rare. Here, we report one such case of duodenal bulb adenocarcinoma with neuroendocrine features. A 63-year-old Han Chinese woman was admitted to our department with the diagnosis of a duodenal bulb polyp and underwent an endoscopic mucosal resection. The pathological findings confirmed it as duodenal bulb adenocarcinoma with NEF. The patient remains curative after one and half a years of follow-up. Duodenal adenocarcinoma with NEF might be a low malignant neuroendocrine tumor rather than a conventional adenocarcinoma. Endoscopic treatment, including endoscopic mucosal resection, might be an ideal option for the adenocarcinomas with NEF. PMID- 26140013 TI - Convex Clustering with Exemplar-Based Models. AB - Clustering is often formulated as the maximum likelihood estimation of a mixture model that explains the data. The EM algorithm widely used to solve the resulting optimization problem is inherently a gradient-descent method and is sensitive to initialization. The resulting solution is a local optimum in the neighborhood of the initial guess. This sensitivity to initialization presents a significant challenge in clustering large data sets into many clusters. In this paper, we present a different approach to approximate mixture fitting for clustering. We introduce an exemplar-based likelihood function that approximates the exact likelihood. This formulation leads to a convex minimization problem and an efficient algorithm with guaranteed convergence to the globally optimal solution. The resulting clustering can be thought of as a probabilistic mapping of the data points to the set of exemplars that minimizes the average distance and the information-theoretic cost of mapping. We present experimental results illustrating the performance of our algorithm and its comparison with the conventional approach to mixture model clustering. PMID- 26140014 TI - Injection System for Multi-Well Injection Using a Single Pump. AB - Many hydrological and geochemical studies rely on data resulting from injection of tracers and chemicals into groundwater wells. The even distribution of liquids to multiple injection points can be challenging or expensive, especially when using multiple pumps. An injection system was designed using one chemical metering pump to evenly distribute the desired influent simultaneously to 15 individual injection points through an injection manifold. The system was constructed with only one metal part contacting the fluid due to the low pH of the injection solutions. The injection manifold system was used during a three month pilot scale injection experiment at the Vineland Chemical Company Superfund site. During the two injection phases of the experiment (Phase I = 0.27 L/min total flow, Phase II = 0.56 L/min total flow), flow measurements were made 20 times over three months; an even distribution of flow to each injection well was maintained (RSD <4%). This durable system is expandable to at least 16 injection points and should be adaptable to other injection experiments that require distribution of air-stable liquids to multiple injection points with a single pump. PMID- 26140015 TI - Goniothalamusflagellistylus Tagane & V. S. Dang (Annonaceae), a new species from Mt. Hon Ba, Vietnam. AB - A new species, Goniothalamusflagellistylus Tagane & V. S. Dang, sp. nov. from Hon Ba Nature Reserve in Khanh Hoa Province, South Vietnam is described and illustrated. This species is most similar to Goniothalamustortilipetalus M.R.Hend., but distinct in having 308-336 stamens (vs. ca. 170-260) and ca.120 carpels (vs. ca. 50-100) per flower, and Stigma and pseudostyles ca.8.5 mm (vs. 4 4.5 mm) long. PMID- 26140016 TI - Lectotypification of names of Himalayan Brassicaceae taxa currently placed in the genus Cardamine. AB - Lectotypes of twenty-eight names of taxa currently recognized or synonymized in Cardamine are designated as part of the work on the account of the genus for the Pan-Himalayan Flora. Among them, the previous first-step lectotypification of the name Cardaminecalthifolia is finalized. In cases when specimen images are available online, stable identifiers for specimens, other permanent links, or links via JSTOR Global Plants are provided. PMID- 26140017 TI - The correct name in Oenothera for Gauradrummondii (Onagraceae). AB - In 2007, Wagner and Hoch proposed the new name Oenotheraxenogaura W.L.Wagner & Hoch for the species then known as Gauradrummondii (Spach) Torrey & A. Gray (non Oenotheradrummondii Hooker, 1834). However, the authors overlooked the availability of Gaurahispida Bentham (1840) for this species. Accordingly, we herewith make the appropriate new combination for this species, Oenotherahispida (Bentham) W.L.Wagner, Hoch & Zarucchi, and place Oenotheraxenogaura in synonymy. PMID- 26140018 TI - The correct name for a section of Ludwigia L. (Onagraceae). AB - In 1953, Hara provided new combinations for many sectional and species names when he combined Jussiaea L. with Ludwigia L., and at the time, Ludwigiasect.Oligospermum (Micheli) H.Hara was the correct name for one well defined section. However, subsequent changes to/clarifications of the botanical code have necessitated a change for that name in that now an autonym is treated as having priority over the name or names of the same date and rank that established it. Since Hara's combination was based on Jussiaeasect.Oligospermum Micheli, the correct name for this section is Ludwigiasect.Jussiaea (L.) Hoch, W.L.Wagner, & P.H.Raven. PMID- 26140019 TI - Eremogone (Caryophyllaceae): new combinations for Old World species. AB - Twenty-one new combinations in Eremogone (Eremogoneae, Caryophyllaceae) are proposed to accommodate placement of all Old World taxa of Arenariasubg.Eremogone and Eremogoneastrum within Eremogone. PMID- 26140020 TI - A new species of Brevianthus (Brevianthaceae, Marchantiophyta) from New Caledonia with unusual underleaf production. AB - Brevianthus is a distinctive genus of leafy liverwort in its succubously inserted, entire leaves, lack of underleaves, restriction of sexual organs to lateral-intercalary branches, scattered rhizoids and dense leaf-surface ornamentation. The sole species, Brevianthusflavus, is divided into two subspecies, one in Tasmania the other in New Zealand. A second species, Brevianthushypocanthidium, is described as new and is the first record of the genus for New Caledonia. Among its distinguishing characters are its shallowly bilobed leaves, and triangular underleaves present on small to medium-sized shoot sectors, the lack of a hyaline leaf margin, and the crenulate leaf margin formed by heavily thickened external cell walls. The most unusual features of the new species are the presence of underleaves between lateral leaf insertion lines that reach the ventral stem mid-line, and the absence of underleaves from larger shoots. To explain these features we propose a competitive model of shoot formation wherein the ventral merophyte progressively loses vigor as its relative stature decreases, and its derivative cells become discontinuous and isolated along the ventral stem surface, with intervening areas occupied by derivatives of the more vigorous lateral merophytes. PMID- 26140021 TI - Seven new species of Selaginellasubg.Stachygynandrum (Selaginellaceae) from Brazil and new synonyms for the genus. AB - We describe seven new species of Selaginellasubg.Stachygynandrum (Selaginellaalstonii, Selaginellablepharodella, Selaginellacrinita, Selaginellamucronata, Selaginellamucugensis, Selaginellasaltuicola, and Selaginellasematophylla) from Brazil and discuss their possible affinities and conservation status. Scanning electron micrographs of stem sections, leaves, and spores are provided to illustrate the new taxa. In Selaginellaalstonii and Selaginellasaltuicola vegetative growth from strobilus tips is reported and discussed. Four of the new species are from the Espinhaco Mountain Range associated with Campos Rupestres (montane savannah/rocky fields) vegetation. Three of these (i.e., Selaginellablepharodella, Selaginellacrinita, and Selaginellamucugensis) were collected in the northern part of the range in Chapada Diamantina, state of Bahia, while Selaginellaalstonii is from the southern part of the range in the state of Minas Gerais. Selaginellamucronata is found in Atlantic Rainforest vegetation in the state of Espirito Santo, whereas Selaginellasaltuicola inhabits Cerrado (tropical savannah) vegetation in the state of Mato Grosso. Selaginellasematophylla is the most widely distributed of the new species and was collected in Espirito Santo, Minas Gerais, and Rio de Janeiro states in Campos Rupestres and Atlantic Rainforest vegetation. Selaginellaalstonii occurs in rocky caves, Selaginellablepharodella, Selaginellacrinita, Selaginellamucugensis, and Selaginellasematophylla seem adapted to seasonally dry places, living on sandy or humid soils, Selaginellamucronata occupies humid, forest understory, and Selaginellasaltuicola is adapted to wet places associated with rocks or logs in waterfalls. Of the seven new species, six are considered local endemics (except for Selaginellasematophylla) because of their restricted currently known distributions to one or two localities within a single state in Brazil. Additionally, we propose new synonymy for Selaginellapalmiformis (syn. = Selaginellabahiensissubsp.manausensis, = Selaginellamanausensis) and Selaginellavestiens (syn. = Selaginellafragillima); the last species is endemic to Brazil, recorded in the states of Goias and Minas Gerais. Finally, based on literature discussed and this study, we conclude that the number of well documented Brazilian Selaginella species is 61, of which 58 are native and three introduced and naturalized. These statistics are likely to change with further work on Selaginella from Brazil. PMID- 26140022 TI - The resurrection of Neohattoria Kamim. (Jubulaceae, Marchantiophyta): a six decade systematic conflict resolved through a molecular perspective. AB - The systematic placement of Frullaniaherzogii has been contentious since its description six decades ago. Over the years it has been interpreted as either a member of the genus Frullania or segregated into its own genus, Neohattoria, due to morphological similarities with both Frullania and Jubula. Here we provide molecular evidence that supports the recognition of the genus Neohattoria and its inclusion within the Jubulaceae, together with Jubula and Nipponolejeunea. Jubulaceae are placed sister to Lejeuneaceae rather than to the monogeneric Frullaniaceae. PMID- 26140023 TI - A foundation monograph of Convolvulus L. (Convolvulaceae). AB - A global revision of Convolvulus L. is presented, Calystegia R.Br. being excluded on pragmatic grounds. One hundred and ninety species are recognised with the greatest diversity in the Irano-Turanian region. All recognised species are described and the majority are illustrated. Distribution details, keys to species identification and taxonomic notes are provided. Four new species, Convolvulusaustroafricanus J.R.I.Wood & R.W.Scotland, sp. nov., Convolvulusiranicus J.R.I.Wood & R.W.Scotland, sp. nov., Convolvuluspeninsularis J.R.I.Wood & R.W.Scotland, sp. nov. and Convolvulusxanthopotamicus J.R.I.Wood & R.W.Scotland, sp. nov., one new subspecies Convolvuluschinensissubsp.triangularis J.R.I.Wood & R.W.Scotland, subsp. nov., and two new varieties Convolvulusequitansvar.lindheimeri J.R.I.Wood & R.W.Scotland, var. nov., Convolvulusglomeratusvar.sachalitarum J.R.I.Wood & R.W.Scotland, var. nov. are described. Convolvulusincisodentatus J.R.I.Wood & R.W.Scotland, nom. nov., is provided as a replacement name for the illegitimate Convolvulusincisus Choisy. Several species treated as synonyms of other species in recent publications are reinstated including Convolvuluschinensis Ker-Gawl., Convolvulusspinifer M.Popov., Convolvulusrandii Rendle and Convolvulusaschersonii Engl. Ten taxa are given new status and recognised at new ranks: Convolvulusnamaquensis (Schltr. ex. A.Meeuse) J.R.I.Wood & R.W.Scotland, stat. nov., Convolvulushermanniaesubsp.erosus (Desr.) J.R.I.Wood & R.W.Scotland, stat. nov., Convolvuluscrenatifoliussubsp.montevidensis (Spreng.) J.R.I.Wood & R.W.Scotland, stat. nov., Convolvulusfruticulosussubsp.glandulosus (Webb) J.R.I.Wood & R.W.Scotland, stat. nov., Convolvuluscapituliferussubsp.foliaceus (Verdc.) J.R.I.Wood & R.W.Scotland, stat. nov., Convolvulushystrixsubsp.ruspolii (Dammer ex Hallier f.) J.R.I.Wood & R.W.Scotland, stat. nov., Convolvulushystrixsubsp.inermis (Chiov.) J.R.I.Wood & R.W.Scotland, stat. nov., Convolvulusrottlerianussubsp.stocksii (Boiss.) J.R.I.Wood & R.W.Scotland, comb. et stat. nov., Convolvuluscalvertiisubsp.ruprechtii (Boiss.) J.R.I.Wood & R.W.Scotland, stat. nov., Convolvuluscephalopodussubsp.bushiricus (Bornm.) J.R.I.Wood & R.W.Scotland, stat. nov. The status of various infraspecific taxa is clarified and numerous taxa are lectotypified. This account represents a new initiative in terms of taxonomic monography, being an attempt to bring together the global approach of the traditional monograph with the more pragmatic and identification-focussed approach of most current floras while at the same time being informed by insights from molecular systematics. PMID- 26140024 TI - Annual sulfur cycle in a warm monomictic lake with sub-millimolar sulfate concentrations. AB - BACKGROUND: We studied the annual variability of the concentration and isotopic composition of main sulfur species and sulfide oxidation intermediates in the water column of monomictic fresh-water Lake Kinneret. Sulfate concentrations in the lake are <1 mM and similar to concentrations that are proposed to have existed in the Paleoproterozoic ocean. The main goal of this research was to explore biogeochemical constrains of sulfur cycling in the modern low-sulfate fresh-water lake and to identify which processes may be responsible for the isotopic composition of sulfur species in the Precambrian sedimentary rocks. RESULTS: At the deepest point of the lake, the sulfate inventory decreases by more than 20% between March and December due to microbial sulfate reduction leading to the buildup of hydrogen sulfide. During the initial stages of stratification, sulfur isotope fractionation between sulfate and hydrogen sulfide is low (11.6 0/00) and sulfur oxyanions (e.g. thiosulfate and sulfite) are the main products of the incomplete oxidation of hydrogen sulfide. During the stratification and at the beginning of the lake mixing (July-December), the inventory of hydrogen sulfide as well as of sulfide oxidation intermediates in the water column increases and is accompanied by an increase in sulfur isotope fractionation to 30 +/- 4 0/00 in October. During the period of erosion of the chemocline, zero-valent sulfur prevails over sulfur oxyanions. In the terminal period of the mixing of the water column (January), the concentration of hydrogen sulfide decreases, the inventory of sulfide oxidation intermediates increases, and sulfur isotope fractionation decreases to 20 +/- 2 0/00. CONCLUSIONS: Sulfide oxidation intermediates are present in the water column of Lake Kinneret at all stages of stratification with significant increase during the mixing of the water column. Hydrogen sulfide inventory in the water column increases from March to December, and sharply decreases during the lake mixis in January. Sulfur isotope fractionation between sulfate and hydrogen sulfide as well as concentrations of sulfide oxidation intermediates can be explained either by microbial sulfate reduction alone or by microbial sulfate reduction combined with microbial disproportionation of sulfide oxidation intermediates. Our study of sulfur cycle in Lake Kinneret may be useful for understanding the range of biogeochemical processes in low sulfate oceans over Earth history. PMID- 26140025 TI - Quantitative Point-of-Care Pathogen Detection in Septicemia. AB - Pathogen nucleic acid detection exhibits faster turnaround times and higher sensitivity compared with blood culture. When antibiotics are present, blood cultures experience higher false-negative rates. In contrast, nucleic acid tests may detect pathogens irrespective of antimicrobial therapy. Thus, future point-of care nucleic acid-based detection devices could play a role in revolutionizing pathogen detection in critically ill patients. To properly optimize clinical use, pathogen nucleic acid tests should have the capacity to quantitate pathogen DNA, be miniaturized with simplified preanalytical and postanalytical processing components, and reduce net operating costs or provide clear-cut clinical outcome benefits. These 3 elements will foster a new generation of nucleic acid tests for use at the point of need and facilitate a paradigm shift to point-of-care pathogen detection with evidence-based treatment and real-time quantitative monitoring of patients with sepsis. PMID- 26140026 TI - A Commitment to the Vision of Our Journal. PMID- 26140027 TI - Large Hill-Sachs Lesion: a Comparative Study of Patients Treated with Arthroscopic Bankart Repair with or without Remplissage. AB - BACKGROUND: There is little comparative long-term clinical data comparing Bankart repair alone to the addition of remplissage. QUESTIONS/PURPOSES: Our purpose was to compare results of patients with significant humeral head lesions and who underwent either isolated arthroscopic Bankart repair or remplissage. METHODS: This is a retrospective cohort study of 14 isolated arthroscopic Bankart and 10 remplissage repairs all with large engaging Hill-Sachs (HS) lesions. Average follow-up was 40.72 months (26.3-51.1) in the Bankart group and 31.55 months (24.1-39.9) in the remplissage group. Surgical failure was defined as a dislocation or subluxation. Groups were matched on handedness, age within 3 years, and HS lesion size. Glenoid bone loss and HS size were measured on MRI. Additionally, WOSI and DASH scores were obtained. RESULTS: The average age at surgery was 26.0 years (17.8-41.1) of the isolated Bankart patient and 24.4 years (16.4-38.3) in the remplissage group. The average HS lesion volume was 310.22 mm(3) in the Bankart group and 283.79 mm(3) in the remplissage group. The failure rate for the Bankart group was 8 out of 14 patients (57.14%). For the remplissage group, the failure rate was 2 out of 10 patients (20.0%). Average WOSI scores were 73.72 in the Bankart group and 79.54 in the remplissage group. For DASH scores, the average Disability/Symptoms Scores were 16.23 for the Bankart group and 12.05 for the remplissage patients. CONCLUSIONS: In comparison to isolated Bankart repair, remplissage was a superior option for recurrent instability patients with large Hill-Sachs lesions as seen by diminished failure rates and improved outcome scores. PMID- 26140028 TI - Bone Mesenchymal Stem Cells with Growth Factors Successfully Treat Nonunions and Delayed Unions. AB - BACKGROUND: While the gold standard of treatment of nonunion is open autologous bone grafting, studies have shown that injecting bone marrow aspirate concentrates (BMAC) is effective in treating tibial nonunions with fracture gaps less than 5 mm. QUESTIONS/PURPOSES: We aim to demonstrate that combining BMAC with osteoinductive agents can effectively treat delayed or nonunion regardless of fracture gap size, nonunion site, or osteoinductive agent used. METHODS: In this non-randomized retrospective-prospective cohort study, 49 patients with tibial nonunion met the inclusion criteria and underwent BMAC injection with demineralized bone matrix (DBM) and/or recombinant human bone morphogenic protein 2 (rhBMP-2). Radiologic healing of the fracture was the primary outcome. Patients were followed until radiographic union was achieved or another procedure was performed. Radiographic healing was defined as bridging of three out of four cortices on anteroposterior and lateral films. RESULTS: There was no difference in the healing rate (p = 0.81) between patients with fracture gaps less than and greater than 5 mm. On multivariate analysis, the use of rhBMP-2 was associated with a lower healing rate compared to DBM (p = 0.036). Patients who underwent early intervention (within 6 months of fixation) had higher union rates (p = 0.04). CONCLUSION: This study shows that percutaneous BMAC injection combined with either DBM and/or rhBMP-2 is a safe and effective treatment for delayed or nonunion regardless of the fracture gap size or fracture site. DBM may be superior to rhBMP-2 in this procedure. PMID- 26140029 TI - An Analysis of Risk Factors for Short-Term Complication Rates and Increased Length of Stay Following Unicompartmental Knee Arthroplasty. AB - BACKGROUND: Unicompartmental knee arthroplasty (UKA) is an increasingly popular procedure, with excellent long-term outcomes. However, there are only a limited number of reports reporting its short-term morbidity and mortality. QUESTIONS/PURPOSES: We sought to analyze the reported 30-day morbidity, mortality, and risk factors for complications and prolonged length of stay (>4 days) following UKA. PATIENTS AND METHODS: Utilizing the National Surgical Quality Improvement Program (NSQIP) database, including patients (n = 2316) from 2005-2012, we correlated the reported 30-day complications and prolonged length of stay with patient demographics and risk factors. RESULTS: The overall rate of complications was low (3.2%). The distribution of complications demonstrated 0.5% major systemic, 1.4% minor systemic, 0.7% major local, and 0.9% minor local complications, with a 2.1% readmission rate. Multivariate regression demonstrated increased BMI and a history of chronic obstructive pulmonary disease (COPD) as independent risk factors for complications. Furthermore, multivariate regression demonstrated increased BMI, ASA >= 3, history of COPD, recent operation, and postoperative transfusion as independent risk factors for prolonged length of hospitalization. CONCLUSIONS: Utilizing the NSQIP, we present one of the largest studies to date evaluating complications following UKA. Our multivariate model demonstrated obesity and COPD to be the risk factors for complications while obesity, ASA >= 3, COPD, recent operation, and blood transfusion to be the risk factors for prolonged length of stay. PMID- 26140030 TI - An Anatomic Study on Whether the Patella is Centered in an Ideal Anteroposterior Radiograph of the Knee. AB - BACKGROUND: Currently, an anteroposterior radiograph of the knee is judged based on a centered position of the patella between the femoral condyles. We are not aware of any anatomic literature supporting this recommendation. QUESTIONS/PURPOSES: Orthogonal images are required for accurate assessment of knee deformity. Although an image with the patella centered at the distal femur is generally accepted as a true anteroposterior (AP) radiograph of the knee, there is minimal anatomic data to support that this view is orthogonal to a true lateral view of the knee where the condyles are overlapped. We designed an anatomical study to test the relationship between these two radiographic views. METHODS: We studied 428 well-preserved cadaveric skeletons ranging from 40 to 79 years of age at death. Centering of the patella was calculated based on distal femoral and patellar widths. Multiple regression analysis was then performed to determine the relationship between patellar centering and age, gender, ethnicity, mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), femoral anteversion, and contralateral centering. RESULTS: Average patellar centering was 0.13 +/- 0.04, indicating that the average patella was laterally positioned in the distal femur. Only mLDFA and contralateral centering showed statistically significant independent correlations with patellar centering with modest standardized beta coefficients of 0.10 and 0.23, respectively. CONCLUSIONS: In the average specimen, the patella is laterally deviated by 13% of the condylar width. Clinicians should be aware that a lateral view with the femoral condyles overlapped is not always orthogonal to a patella-centered AP view when planning and implementing deformity correction. PMID- 26140031 TI - Quantitative Ultrashort Echo Time Magnetic Resonance Imaging Evaluation of Postoperative Menisci: a Pilot Study. AB - BACKGROUND: Magnetic resonance imaging (MRI) visualization of meniscal signal is particularly challenging as the highly organized ultrastructure of meniscal fibrocartilage yields very short T2 values (~6 ms) and a paucity of signal intensity during conventional image acquisition. QUESTION/PURPOSE: The purpose of this study was to evaluate the feasibility of imaging postoperative menisci using an experimental, quantitative ultrashort echo time (UTE) MRI pulse sequence. This sequence acquires short echo images (echo time (TE) ~0.3 ms) to produce multi echo images for quantitative T2* calculations that provide an objective measure of collagen organization. PATIENTS AND METHODS: MRI scans of the knee were acquired at 6- and 12-month intervals on a clinical 3.0 T scanner following meniscal surgery in eight patients (ages 13-41), four of whom underwent repair and the other four partial meniscectomy. Conventional MRI sequences were qualitatively evaluated for meniscal morphology and signal and correlated with quantitative UTE results. RESULTS: A wide range of mean T2* values for both postsurgical groups was measured, and these values changed for each patient between the 6- and 12-month intervals. In many instances, the UTE sequence demonstrated quantitative differences between the two time intervals that were not detected with conventional sequences. CONCLUSIONS: This pilot study presents preliminary, observational data to be used as a baseline for future studies. Although the T2* values did not reveal a trend in either group or correlate with expected signal changes on conventional MRI, we speculate that the UTE sequence may detect ultrastructural alterations in meniscal composition that are otherwise not perceived with routine fast spin echo (FSE) sequences. PMID- 26140032 TI - Two Year Clinical Outcomes of Total Hip Arthroplasty Are Not Dependent on Femoral Head Composition. AB - BACKGROUND: Assessment of clinical outcomes and patient quality of life after total hip arthroplasty continues to grow in importance with the focus on how bearing surfaces affect long-term survival, wear, and cost. Further, as quality measures have become incorporated into reimbursement, there is a need to quantify factors which may influence these outcomes. Currently, there is a paucity of literature regarding the effects of the femoral head composition on clinical outcomes or quality of life. QUESTIONS/PURPOSES: We sought to determine if any difference in quality of life measures could be detected in patients treated with total hip replacement implanted with cobalt-chrome (CoCr) versus ceramic femoral heads at 2-year follow-up. METHODS: We compared the hip disability and osteoarthritis outcome score (HOOS) and EuroQOL (EQ5D) scores of a matched set of patients that underwent primary total hip arthroplasty with highly cross-linked polyethylene (HXLPE) and a single implant system consisting of either a metal or a ceramic femoral head. RESULTS: Clinical outcomes and quality of life improved for both groups after hip replacement surgery. Patients with a ceramic head showed greater improvement than those with a metal head in HOOS pain and EQ5D VAS scores by a statistically significant margin (p = 0.0417 and 0.019, respectively), but the differences between the HOOS and EQ5D VAS scores (3.4 and 0.04, respectively) do not demonstrate a clinically significant difference. CONCLUSIONS: We found that the femoral head composition has no effect on clinical outcomes or patient quality of life at 2 years. PMID- 26140033 TI - Blood Transfusions May Have Limited Effect on Muscle Oxygenation After Total Knee Arthroplasty. AB - BACKGROUND: Traditionally, blood transfusions in the perioperative setting are used to maintain adequate delivery of nutrients and oxygen to organs. However, the effect of blood administration on tissue oxygenation in the perioperative setting remains poorly understood. QUESTIONS/PURPOSES: The aim of this study was to determine changes in muscle tissue oxygenation saturation (SmO2) in response to perioperative blood transfusions. PATIENTS AND METHODS: Patients undergoing total knee arthroplasty were enrolled. SmO2, continuous hemoglobin (SpHb), stroke volume (SV), cardiac index, and standard hemodynamic parameters including heart rate (HR), mean arterial blood pressure (MAP), and arterial oxygen saturation (SO2) were recorded. To assess fluid responsiveness, a passive leg raise (PLR) test was performed before the transfusions were started. RESULTS: Twenty-eight patients were included in the analysis. Mean (+/-SD) SmO2 before transfusion was 63.18 +/- 10.04%, SpHb was 9.27 +/- 1.16 g/dl, and cardiac index was 2.62 +/- 0.75 L/min/m(2). A significant increase during the course of blood transfusion was found for SmO2 (+3.44 +/- 5.81% [95% confidence interval (CI) 1.04 to 5.84], p = 0.007), SpHb (0.74 +/- 0.92 g/dl [95% CI 0.35 to 1.12], p < 0.001), and cardiac index (0.38 +/- 0.51 L/min/m2 [95% CI 0.15 to 0.60], p = 0.002), respectively. However, the correlation between SmO2 and SpHb over the course of the transfusion was negligible (rho = 0.25 [95% CI -0.03 to 0.48]). A similar lack of correlation was found when analyzing data of those patients who showed a positive leg raise test before the start of the transfusion (rho = 0.37 [95% CI 0.11 to 0.84]). CONCLUSION: We detected a statistically significant increase in SmO2 during the course of a single unit blood transfusion compared to baseline. However, there was no evidence of a correlation between longitudinal SmO2 and SpHb measurements. PMID- 26140034 TI - A Novel Assessment of Braking Reaction Time Following THA Using a New Fully Interactive Driving Simulator. AB - BACKGROUND: After total hip replacement surgery, patients are eager to resume the activities of daily life, particularly driving. Most surgeons recommend waiting 6 weeks after surgery to resume driving; however, there is no evidence to indicate that patients cannot resume driving earlier. QUESTIONS/PURPOSES: Our purpose was to evaluate when in the recovery period following THA that patients regain or improve upon their preoperative braking reaction time, allowing them to safely resume driving. METHODS: We measured and compared pre- and postoperative braking reaction times of 90 patients from 3 different surgeons using a Fully Interactive Driving Simulator (Simulator Systems International, Tulsa, OK). We defined a return to safe braking reaction time as a return to a time value that is either equal to or less than the preoperative braking reaction time. RESULTS: Patients tested at 2 and 3 weeks after surgery had slower braking reaction times than preoperative times by an average of 0.069 and 0.009 s, respectively. At 4 weeks after surgery, however, patients improved their reaction times by 0.035 s (p = 0.0398). In addition, at 2, 3, and 4 weeks postoperatively, the results also demonstrated that patient less than 70 years of age recovered faster. CONCLUSIONS: Based upon the results of this study, most patients should be allowed to return to driving 4 weeks following minimally invasive primary total hip arthroplasty. PMID- 26140035 TI - Clinical Comparison of Minifragment Plates Versus Conventional Semitubular Plates for Fixation of Distal Fibula Fractures. AB - BACKGROUND: Although operative stabilization of unstable distal fibula fractures is frequently performed and discussed, the ideal implant and technique for these injuries is still debated. QUESTIONS/PURPOSES: The purpose of this study was to determine if minifragment plating of distal fibula fractures would clinically provide equivalent fixation and cost and minimize hardware prominence when compared with standard one-third tubular plating. PATIENTS AND METHODS: A retrospective review was conducted on 44 patients who had undergone operative stabilization of a displaced fibula fracture. Inclusion required fibula fixation with either a traditional one-third semitubular plate or a 2.7-mm minifragment plate. Retrospective review of the patient demographics, injury and surgical variables, and radiographs was completed by two surgeons not involved with the patients' original care. RESULTS: The minifragment group demonstrated equivalency in maintenance of fracture reduction relative to standard tubular plating. Both groups were able to maintain the talocrural angle with less than 1 degrees of change from initial postoperative to final postoperative radiographs. No significant differences were seen in postoperative hardware irritation between groups. CONCLUSIONS: Use of a minifragment plating system for displaced fibula fractures appears to be safe but comes with the significant potential added cost of the technology. Interestingly, no significant differences were seen in implant related irritation or implant removal, but further investigation with a larger study population would help better determine these outcomes. PMID- 26140036 TI - Radiographic Anatomy of the Native Anterior Cruciate Ligament: a Systematic Review. AB - BACKGROUND: In an attempt to improve the accuracy and reproducibility of tunnel positioning, radiographs are being analyzed in an attempt to recreate the native anatomy of the ACL. Understanding the native ACL radiographic anatomy is an essential prerequisite to understand the relevance of postoperative tunnel position. QUESTIONS/PURPOSES: We performed a systematic review of the literature to delineate the radiographic location of the native ACL femoral and tibial footprints. METHODS: A search was performed in March 2014 in PubMed, the Cochrane Collaboration Library, and EMBASE to identify all studies that evaluated the native anterior cruciate ligament (ACL) anatomy on radiographs. Various measurement methods were used in each study, and averages were obtained of the data from studies with the same measurement methods. RESULTS: Fifteen papers were identified (which included data on 177 femora and 207 tibiae in total). Evaluation of the femoral footprint using the quadrant method on lateral knee radiographs showed that the average percent distance location of the anteromedial (AM) bundle and posterolateral (PL) bundle was 22.8% (95% confidence interval (CI) 16.59-28.90) and 32.5% (95% CI 27.71-37.26) from the posterior condyle, respectively, and 23.2% (95% CI 19.52-26.94) and 50.0% (95% CI 46.16-53.76) from Blumensaat's line, respectively. Using the Amis and Jacob method, the tibial footprint on the lateral knee radiograph average percent distances was 35.1% (95% CI 34.46-35.72) for the center of the AM bundle and 47.3% (95% CI 41.69-52.95) for the center of the PL bundle of the ACL. The femoral and tibial ACL footprints on the anteroposterior (AP) views of the knee were not well delineated by these studies. CONCLUSION: The information presented in this systematic review offers surgeons another important tool for accurate ACL footprint identification. PMID- 26140037 TI - Suboptimal Component Position Leading to Severe Wear of an Alumina-Alumina Total Hip Coupling: Biomechanical Analysis and Documentation of Limited Tissue Response. PMID- 26140038 TI - Failure of a Knee Joint Load Absorber: Pain, Metallosis and Soft Tissue Damage. PMID- 26140039 TI - Ligament Reconstruction in Congenital Absence of the Anterior Cruciate Ligament: A Report of Two Cases. PMID- 26140040 TI - Rapidly Progressive Cardiac Failure Due to Giant Cell Myocarditis: A Clinical Pathology Conference Held by the Division of Rheumatology at Hospital for Special Surgery. PMID- 26140041 TI - Operative Treatment of Thoracolumbar Burst Fractures: Is Fusion Necessary? PMID- 26140042 TI - The Role of Dendritic Cells in Central Tolerance. AB - Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions. PMID- 26140043 TI - Is CD137 Ligand (CD137L) Signaling a Fine Tuner of Immune Responses? AB - Now, it has been being accepted that reverse signaling through CD137 ligand (CD137L) plays an important role in vivo during hematopoiesis and in immune regulation. However, due to technical difficulty in dissecting both directional signaling events simultaneously in vivo, most biological activities caused by CD137-CD137L interactions are considered as results from signaling events of the CD137 receptor. To make the story more complex, CD137(-/-) and CD137L(-/-) mice have increased or decreased immune responses in a context-dependent manner. In this Mini review, I will try to provide a plausible explanation for how CD137L signaling is controlled during immune responses. PMID- 26140044 TI - Attenuation of Hepatic Graft-versus-host Disease in Allogeneic Recipients of MyD88-deficient Donor Bone Marrow. AB - Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft. PMID- 26140045 TI - Alloferon Alleviates Dextran Sulfate Sodium-induced Colitis. AB - Dysfunction of gut immune regulation is involved in mucosal damage in inflammatory bowel disease (IBD). However, there is still no efficacious immune regulator for the treatment of IBD. Alloferon is a novel immune-modulatory peptide that was originally isolated from infected insects. It shows anti inflammatory effects by the regulation of cytokine production by immune cells and their activities. Therefore, we investigated the effect of alloferon in a mouse model of colitis using dextran sulfate sodium (DSS). Colitis was induced by administration of DSS in drinking water for 7 consecutive days. It was confirmed by the presence of weight loss, diarrhea, hematochezia, and colon contraction. Alloferon was injected 4 days after DSS administration. We found that alloferon improved the pathogenesis of IBD based on the reduced disease activity index (DAI) and colon contraction. Edema, epithelial erosion, and immune cell infiltration were found in mice administered DSS, but the phenomena were reduced following alloferon treatment. The plasma level of IL-6, a classical pro inflammatory cytokine in colitis, was also decreased by alloferon. Moreover, alloferon inhibited the TNF-alpha-induced degradation and phosphorylation of IkappaB in Colo205 colon cancer cells. Taken together, these results show that alloferon has anti-inflammatory effects and attenuates DSS-induced colitis. PMID- 26140046 TI - Osteopontin Potentiates Pulmonary Inflammation and Fibrosis by Modulating IL 17/IFN-gamma-secreting T-cell Ratios in Bleomycin-treated Mice. AB - Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPN-deficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of CD4(+) alphabeta T cells and IL-17-producing gammadelta T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of CD4(+) alphabeta T cells and the percentage of IFN-gamma-producing gammadelta T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in CD4(+) T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-gamma T cells. PMID- 26140047 TI - Effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Immune Functions in Healthy Adults in a Randomized Controlled Trial. AB - We previously reported that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) accelerates hematopoiesis and has an improving effect on animal disease models such as sepsis and asthma. The effects of PLAG supplementation on immune modulation were assessed in healthy men and women. The objective was to evaluate the effects of PLAG supplementation on immune regulatory functions such as activities of immune cells and cytokine production. A randomized double blind placebo-controlled trial was conducted. Seventy-five participants were assigned to one of two groups; all participants had an appropriate number of white blood cells on the testing day. The PLAG group (n=27) received oral PLAG supplements and the control group (n=22) received oral soybean oil supplements. IL-4 and IL-6 production by peripheral blood mononuclear cells (PBMC) were lower (p<0.001 and p<0.001, respectively) with PLAG than with soybean oil. However, the production of IL-2 and IFN-gamma by PBMC was unaltered with PLAG supplementation. The B cell proliferation decreased significantly in the PLAG group compared to the soybean oil control (p<0.05). The intake of PLAG in healthy adults for 4 weeks was deemed safe. These data suggest that PLAG has an immunomodulatory function that inhibits the excessive immune activity of immunological disorders such as atopic and autoimmune diseases. PLAG could improve the condition of these diseases safely as a health food supplement. PMID- 26140048 TI - Early Growth Response-1 Plays a Non-redundant Role in the Differentiation of B Cells into Plasma Cells. AB - Early growth response (Egr)-1 is a Cys2-His2-type zincfinger transcription factor. It has been shown to induce survival and proliferation of immature and mature B cells, respectively, but its role in the differentiation of B cells into plasma cells remains unclear. To examine the effects of Egr-1 deficiency on the activation of B cells, naive B cells from Egr1 (-/-) mice and their wild-type (WT) littermates were activated to proliferate and differentiate, and then assayed by FACS. Proportions of cells undergoing proliferation and apoptosis did not differ between Egr1 (-/-) and WT mice. However, Egr1 (-/-) B cells gave rise to fewer plasma cells than WT B cells. Consistently, Egr1 (-/-) mice produced significantly lower titer of antigen-specific IgG than their WT littermates upon immunization. Our results demonstrate that Egr-1 participates in the differentiation program of B cells into plasma cells, while it is dispensable for the proliferation and survival of mature B cells. PMID- 26140050 TI - Recent XAS studies into Homogeneous metal catalyst in fine chemical and pharmaceutical syntheses. AB - A brief review of studies using X-ray Absorption Spectroscopy (XAS) to investigate homogeneous catalytic reactions in fine chemical and pharmaceutical context since 2010 is presented. The advantages of the techniques over traditional lab-based analytical tools, particularly when NMR spectroscopy fails to deliver mechanistic insights, are summarised using these examples. A discussion on the current limitations of the techniques and challenges in the near future is also included. Graphical abstractA minireview of recent developments in application of X-ray Absorption Spectroscopy as an effective mechanistic tool to synthetic catalytic reactions relevant to fine chemical and pharmaceutical syntheses. PMID- 26140051 TI - Feasibility of trauma-focused cognitive behavioral therapy for traumatized children in Japan: a Pilot Study. AB - BACKGROUND: Trauma-focused cognitive behavioral therapy is used to treat children who have experienced traumatic events and suffer from trauma-related disorders. Its effectiveness has been demonstrated in several randomized controlled studies. However, most of these studies have been performed in the United States, with few studies conducted in Asian countries. Therefore, we aimed to evaluate the feasibility of trauma-focused cognitive behavioral therapy in children who have experienced traumatic events and who suffer from trauma-related disorders in Japan. FINDINGS: Thirty-five traumatized children (mean age = 10.9 years; range = 3-17 years; 74.3% girls) who received trauma-focused cognitive behavioral therapy were included. The effectiveness of the program was evaluated in each case using the University of California at Los Angeles Post-Traumatic Stress Disorder Reaction Index for DSM-IV for trauma-related symptoms and the Children's Global Assessment Scale for social functioning. Pre- and post-treatment outcome measures were analyzed using two-tailed paired t tests. The results for 35 participants indicate that post-traumatic stress symptoms were significantly improved following therapy [t(35) = 8.27; p < 0.01], whereas the assessment of social functioning supported the effectiveness of the program [t(35) = -14.68; p < 0.01]. The pre- to post-treatment effect sizes (Glass's delta) were 1.24 for the University of California at Los Angeles Post-Traumatic Stress Disorder Reaction Index and 1.96 for the Children's Global Assessment Scale. CONCLUSIONS: Our findings indicate that trauma-focused cognitive behavioral therapy is feasible for treating traumatized children of an Asian population. We discuss the implications of this result for clinical practice and future research. PMID- 26140049 TI - Reduced breastfeeding rates among obese mothers: a review of contributing factors, clinical considerations and future directions. AB - Maternal obesity is associated with significantly lower rates of breastfeeding initiation, duration and exclusivity. Increasing rates of obesity among reproductive-age women has prompted the need to carefully examine factors contributing to lower breastfeeding rates in this population. Recent research has demonstrated a significant impact of breastfeeding to reduce the risk of obesity in both mothers and their children. This article presents a review of research literature from three databases covering the years 1995 to 2014 using the search terms of breastfeeding and maternal obesity. We reviewed the existing research on contributing factors to lower breastfeeding rates among obese women, and our findings can guide the development of promising avenues to increase breastfeeding among a vulnerable population. The key findings concerned factors impacting initiation and early breastfeeding, factors impacting later breastfeeding and exclusivity, interventions to increase breastfeeding in obese women, and clinical considerations. The factors impacting early breastfeeding include mechanical factors and delayed onset of lactogenesis II and we have critically analyzed the potential contributors to these factors. The factors impacting later breastfeeding and exclusivity include hormonal imbalances, psychosocial factors, and mammary hypoplasia. Several recent interventions have sought to increase breastfeeding duration in obese women with varying levels of success and we have presented the strengths and weaknesses of these clinical trials. Clinical considerations include specific techniques that have been found to improve breastfeeding incidence and duration in obese women. Many obese women do not obtain the health benefits of exclusive breastfeeding and their children are more likely to also be overweight or obese if they are not breastfed. Further research is needed into the physiological basis for decreased breastfeeding among obese women along with effective interventions supported by rigorous clinical research to advance the care of obese reproductive age women and their children. PMID- 26140052 TI - Essential validation methods for E. coli strains created by chromosome engineering. AB - BACKGROUND: Chromosome engineering encompasses a collection of homologous recombination-based techniques that are employed to modify the genome of a model organism in a controlled fashion. Such techniques are widely used in both fundamental and industrial research to introduce multiple insertions in the same Escherichia coli strain. To date, lambda-Red recombination (also known as recombineering) and P1 phage transduction are the most successfully implemented chromosome engineering techniques in E. coli. However, due to errors that can occur during the strain creation process, reliable validation methods are essential upon alteration of a strain's chromosome. RESULTS AND DISCUSSION: Polymerase chain reaction (PCR)-based methods and DNA sequence analysis are rapid and powerful methods to verify successful integration of DNA sequences into a chromosome. Even though these verification methods are necessary, they may not be sufficient in detecting all errors, imposing the requirement of additional validation methods. For example, as extraneous insertions may occur during recombineering, we highlight the use of Southern blotting to detect their presence. These unwanted mutations can be removed via transducing the region of interest into the wild type chromosome using P1 phages. However, in doing so one must verify that both the P1 lysate and the strains utilized are free from contamination with temperate phages, as these can lysogenize inside a cell as a large plasmid. Thus, we illustrate various methods to probe for temperate phage contamination, including cross-streak agar and Evans Blue-Uranine (EBU) plate assays, whereby the latter is a newly reported technique for this purpose in E. coli. Lastly, we discuss methodologies for detecting defects in cell growth and shape characteristics, which should be employed as an additional check. CONCLUSION: The simple, yet crucial validation techniques discussed here can be used to reliably verify any chromosomally engineered E. coli strains for errors such as non-specific insertions in the chromosome, temperate phage contamination, and defects in growth and cell shape. While techniques such as PCR and DNA sequence verification should standardly be performed, we illustrate the necessity of performing these additional assays. The discussed techniques are highly generic and can be easily applied to any type of chromosome engineering. PMID- 26140053 TI - Construction of a self-cloning system in the unicellular green alga Pseudochoricystis ellipsoidea. AB - BACKGROUND: Microalgae have received considerable interest as a source of biofuel production. The unicellular green alga Pseudochoricystis ellipsoidea (non validated scientific name) strain Obi appears to be suitable for large-scale cultivation in outdoor open ponds for biodiesel production because it accumulates lipids to more than 30 % of dry cell weight under nitrogen-depleted conditions. It also grows rapidly under acidic conditions at which most protozoan grazers of microalgae may not be tolerant. The lipid productivity of this alga could be improved using genetic engineering techniques; however, genetically modified organisms are the subject of regulation by specific laws. Therefore, the aim of this study was to develop a self-cloning-based positive selection system for the breeding of P. ellipsoidea. RESULTS: In this study, uracil auxotrophic mutants were isolated after the mutagenesis of P. ellipsoidea using either ultraviolet light or a transcription activator-like effector nuclease (TALEN) system. The cDNA of the uridine monophosphate synthase gene (PeUMPS) of P. ellipsoidea was cloned downstream of the promoter of either a beta-tubulin gene (PeTUBULIN1) or the gene for the small subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase (PeRBCS) to construct the pUT1 or pUT2 plasmid, respectively. These constructs were introduced into uracil auxotroph strains, and genetically complementary transformants were isolated successfully on minimal agar plates. Use of Noble agar as the solidifying agent was essential to avoid the development of false positive colonies. It took more than 6 weeks for the formation of colonies of pUT1 transformants, whereas pUT2 transformants formed colonies in 2 weeks. Real time PCR revealed that there were more PeUMPS transcripts in pUT2 transformants than in pUT1 transformants. Uracil synthesis (Ura(+)) transformants were also obtained using a gene cassette consisting solely of PeUMPS flanked by the PeRBCS promoter and terminator. CONCLUSIONS: A self-cloning-based positive selection system for the genetic transformation of P. ellipsoidea was developed. Self cloned P. ellipsoidea strains will require less-stringent containment measures for large-scale outdoor cultivation. PMID- 26140054 TI - Uncovering correlated variability in epigenomic datasets using the Karhunen-Loeve transform. AB - BACKGROUND: Larger variation exists in epigenomes than in genomes, as a single genome shapes the identity of multiple cell types. With the advent of next generation sequencing, one of the key problems in computational epigenomics is the poor understanding of correlations and quantitative differences between large scale data sets. RESULTS: Here we bring to genomics a scenario of functional principal component analysis, a finite Karhunen-Loeve transform, and explicitly decompose the variation in the coverage profiles of 27 chromatin mark ChIP-seq datasets at transcription start sites for H1, one of the most used human embryonic stem cell lines. Using this approach we identify positive correlations between H3K4me3 and H3K36me3, as well as between H3K9ac and H3K36me3, so far undetected by the most commonly used Pearson correlation between read enrichment coverages. We uncover highly negative correlations between H2A.Z, H3K4me3, and several histone acetylation marks, but these occur only between principal components of first and second order. We also demonstrate that levels of gene expression correlate significantly with scores of components of order higher than one, demonstrating that transcriptional regulation by histone marks escapes simple one-to-one relationships. This correlations were higher in significance and magnitude in protein coding genes than in non-coding RNAs. CONCLUSIONS: In summary, we present a methodology to explore and uncover novel patterns of epigenomic variability and covariability in genomic data sets by using a functional eigenvalue decomposition of genomic data. R code is available at: http://github.com/pmb59/KLTepigenome. PMID- 26140055 TI - A bioinformatic framework for immune repertoire diversity profiling enables detection of immunological status. AB - BACKGROUND: Lymphocyte receptor repertoires are continually shaped throughout the lifetime of an individual in response to environmental and pathogenic exposure. Thus, they may serve as a fingerprint of an individual's ongoing immunological status (e.g., healthy, infected, vaccinated), with far-reaching implications for immunodiagnostics applications. The advent of high-throughput immune repertoire sequencing now enables the interrogation of immune repertoire diversity in an unprecedented and quantitative manner. However, steadily increasing sequencing depth has revealed that immune repertoires vary greatly among individuals in their composition; correspondingly, it has been reported that there are few shared sequences indicative of immunological status ('public clones'). Disconcertingly, this means that the wealth of information gained from repertoire sequencing remains largely unused for determining the current status of immune responses, thereby hampering the implementation of immune-repertoire-based diagnostics. METHODS: Here, we introduce a bioinformatics repertoire-profiling framework that possesses the advantage of capturing the diversity and distribution of entire immune repertoires, as opposed to singular public clones. The framework relies on Hill-based diversity profiles composed of a continuum of single diversity indices, which enable the quantification of the extent of immunological information contained in immune repertoires. RESULTS: We coupled diversity profiles with unsupervised (hierarchical clustering) and supervised (support vector machine and feature selection) machine learning approaches in order to correlate patients' immunological statuses with their B- and T-cell repertoire data. We could predict with high accuracy (greater than or equal to 80 %) a wide range of immunological statuses such as healthy, transplantation recipient, and lymphoid cancer, suggesting as a proof of principle that diversity profiling can recover a large amount of immunodiagnostic fingerprints from immune repertoire data. Our framework is highly scalable as it easily allowed for the analysis of 1000 simulated immune repertoires; this exceeds the size of published immune repertoire datasets by one to two orders of magnitude. CONCLUSIONS: Our framework offers the possibility to advance immune-repertoire-based fingerprinting, which may in the future enable a systems immunogenomics approach for vaccine profiling and the accurate and early detection of disease and infection. PMID- 26140057 TI - Early resolution of subretinal fluid without high-dose corticosteroids in a pregnant patient with Vogt-Koyanagi-Harada disease: a case report. AB - BACKGROUND: At present, there is no standard of treatment using systemic high dose corticosteroids in cases of pregnant women with Vogt-Koyanagi-Harada (VKH) disease. Although high-dose systemic corticosteroid treatment is often used for VKH disease during pregnancy, it also poses a risk to the fetus. FINDINGS: A 29 year-old woman in the 34th week of pregnancy experienced bilateral metamorphopsia. She had been receiving 5 mg of prednisolone daily for the past 8 years as treatment for rheumatoid arthritis. In order to prevent progression of bilateral serous retinal detachment caused by VKH disease, we recommended the use of high-dose systemic corticosteroids but the patient refused. Thus, we administered only topical ophthalmic betamethasone for mild anterior uveitis. Surprisingly, however, the bilateral bullous retinal detachment healed in just 19 days after the onset of symptoms. A healthy baby was born 1 month later, and sunset glow fundus was subsequently observed without any recurrence of uveitis. CONCLUSIONS: We report a case in which bilateral subretinal fluid caused by VKH disease in a young woman during late pregnancy resolved without high-dose corticosteroid treatment. Pregnancy may have had a beneficial effect on uveitis activity caused by VKH disease. To our knowledge, this report describes the shortest healing period for bilateral bullous retinal detachment in a pregnant woman with VKH disease. PMID- 26140056 TI - Innovative Clinical Trial Designs: Toward a 21st-Century Health Care System. AB - Whereas the 20th-century health care system sometimes seemed to be inhospitable to and unmoved by experimental research, its inefficiency and unaffordability have led to reforms that foreshadow a new health care system. We point out certain opportunities and transformational needs for innovations in study design offered by the 21st-century health care system, and describe some innovative clinical trial designs and novel design methods to address these needs and challenges. PMID- 26140058 TI - The effects of maternal immunity and age structure on population immunity to measles. AB - Measles was successfully eradicated in the Pan-American Health Region in 2002. However, maintenance of elimination in parts of Africa, Europe, the USA, and other regions is proving difficult, despite apparently high vaccine coverage. This may be due to the different age structure in developed and developing populations, as well as to differences in the duration of maternal immunity. We explore the interaction between maternal immunity and age structure and quantify the resulting immunity gap between vaccine coverage and population immunity; we use this immunity gap as a novel metric of vaccine program success as it highlights the difference between actual and estimated immunity. We find that, for some combinations of maternal immunity and age structure, the accepted herd immunity threshold is not maintainable with a single-dose vaccine strategy for any combination of target age and coverage. In all cases, the herd immunity threshold is more difficult to maintain in a population with developing age structure. True population immunity is always improved if the target age at vaccination is chosen for the specific combination of maternal immunity and age structure. PMID- 26140059 TI - An Evaluation of Non-Surgical Periodontal Therapy in Patients with Rheumatoid Arthritis. AB - aim of this study was to evaluate the efficacy of periodontal scaling and oral hygiene instruction for patients with mild chronic periodontitis and rheumatoid arthritis through clinical periodontal parameters and laboratory tests for CRP (C reactive protein) and ESR (erythrocyte sedimentation rate). Twelve individuals with rheumatoid arthritis and 12 healthy individuals were evaluated, with a mean age of 45.38 and 46.75 respectively, all female and with mild, chronic periodontitis. The participants were evaluated clinically and periapical radiographs were taken (T1), after which periodontal treatment was instituted. After ninety days (T2), new clinical and laboratory data were obtained. Probing depth, bleeding index, and plaque indexes were observed in both groups, and the results demonstrated reductions but no statistical differences. Laboratory tests for CRP and ESR produced higher values for the rheumatoid arthritis group with T1 T2 reductions on the average, but the values were still higher than in the health group. We conclude that periodontal therapy in patients with rheumatoid arthritis and mild chronic periodontitis showed a improvement in the periodontal clinical parameters and laboratory tests that were evaluated. PMID- 26140060 TI - Squamous Odontogenic Tumor: Literature Review Focusing on the Radiographic Features and Differential Diagnosis. AB - Since its first publication in 1975, the squamous odontogenic tumor remains the rarest odontogenic lesion, with around 50 cases in the English-language literature in which the microscopic characteristics are frequently very well demonstrated. However, articles which discuss the radiographic aspects are scarce, especially with emphasis on the differential diagnosis. The present treatise proposes an assessment of jaw lesions with the same radiographic characteristics of the squamous odontogenic tumor to clarify the main findings for dental clinicians during routine diagnosis. PMID- 26140061 TI - An Analysis of Background Factors Influencing Selection of Residency Facility for Dental Students in Universities Located in Rural Areas in Japan. AB - BACKGROUND: In Japan, since 2006, participation in a 1-year residency programme by all dentists who have passed the National Board Dental Examination has been mandatory. Therefore, a 'matching system' has become necessary for dental students in their final year to decide their desired residency facility, but the rate of matching in dental schools located in rural areas is still low. Aim : The principal aim of this study was to elucidate the background factors influencing the selection of residency facilities by dental students in rural areas to facilitate the training of dentists working in local communities. Methods : Using the matching results from 554 final-year students of Kagoshima University Faculty of Dentistry from 2005 to 2013, multiple logistic regression analysis was performed on the background factors of the subjects. Results : Concerning the selection of the residency facility, it was verified that there were strong background factors for subjects to select residency facilities in their hometown, but compared with subjects from other regions, those from Kinki and Kanto regions did not select residency facilities in their hometown. Compared with males, a significantly higher number of females selected residency facilities in their hometown. A significantly higher number of subjects who repeated a school year selected the residency facility of their alma mater. Conclusion : In dental schools of national universities located in provinces, the establishment of a quota system for students from the region, where possible, is one of the most effective steps for securing future dental trainees. PMID- 26140062 TI - Evaluation of Biocompatibility of an Etch-and-Rinse Adhesive System Based in Tertiary Butanol Applied in Deep Cavity. AB - The aim of this study was to evaluate biocompatibility of an etch-and-rinse adhesive system based in tertiary butanol applied in deep cavity human teeth with approximately 1 mm of remaining dentin by observing histological changes of the pulp tissue of humans at intervals of 01, 07, 14 and 21 days. Twenty third molars with indication for xtraction from patients of both sexes, presenting no systemic alterations were used. Class I cavity was made deeper and then, XP BOND adhesive system and resin Filtek Z250 were applied. The sample was divided into four groups according to the time intervals between the application of adhesive system and extraction. Morphologic criteria analysed considered the presence of hyperemia, type of inflammatory cell response, organization of odontoblast cells layer, organization of pulp tissue and the presence or absence of bacteria. Data were submitted to Fisher Exact Test p> 0.05. We observed mild inflammatory infiltrate, preserved pulp tissue morphology, disorganization of the odontoblast layer in most specimens, as well as absence of bacteria at the intervals of 01, 07, 14 and 21 days. In some cases there was pulp hyperemia. The etchand- rinse adhesive system based in tertiary butanol showed satisfactory behavior in the conditions studied. PMID- 26140063 TI - Recording the Tilt of a Cast on a Surveyor. AB - Some patients are not satisfied with removable partial dentures (RPDs), when it is not stable during mastication.A dental surveyor can be used to prevent problems related to production of RPDs. Determining the best path of insertion and removal is an initial and fundamental step in RDPs planning. The path of insertion record enables the technician to reproducing the cast in the same position on a surveyor that the dentist selected. This article describes new method for this purpose that could be useful for recording and reproducing the tilt of casts. PMID- 26140064 TI - Awareness of Antimicrobial Prophylaxis for Infective Endocarditis Among Dental Students and Interns at a Teaching Hospital in Jeddah, Saudi Arabia. AB - Introduction : Infective endocarditis is a serious infection of the heart endothelium and valves. It carries long-term health risks and compromises the heart condition. However, this condition has been rarely observed since the introduction of appropriate antibiotic prophylaxis. Dentists play a major role in preventing infective endocarditis in susceptible patients. In this study, we assessed the levels of awareness about antibiotic prophylaxis for infective endocarditis among students and young dentists at King Abdulaziz University, Jeddah, Saudi Arabia. Methods : This cross-sectional study included 367 dental students and dental interns who answered a questionnaire designed to assess their awareness levels; it included questions pertaining to demographic information and questions examining the general knowledge of the participants with regard to antibiotic prophylaxis for infective endocarditis. Results : An average of 50% of the participants clearly lacked knowledge regarding the conditions that require antibiotic prophylaxis, while an average of 65% provided correct answers pertaining to the conditions that do not require prophylaxis. Regarding dental procedures that require prophylaxis, the majority of responses were correct with an average of 71.2%. With regard to the type of antibiotic to be prescribed, 63.5% of the participants chose to prescribe 2 g of amoxicillin as a first-line antibiotic. Conclusion : The results of this study showed that the levels of awareness about antibiotic prophylaxis for infective endocarditis are below 100%. Awareness is essential because of the cardiac risks associated with the lack of appropriate treatment. Up-to-date and accurate knowledge is mandatory for all dental students and interns who see and treat patients on a daily basis. PMID- 26140065 TI - [Leg fractures with intact fibula: casting or intramedullary nailing? (comparative study of 60 cases)]. PMID- 26140066 TI - [Rare case of bilateral rupture of the Achilles tendon with no notion of tendinopathy or ankle surgery in a young athlete: report of a case and review of literature]. PMID- 26140067 TI - Bacteriological assessment of the hospital environment in two referral hospitals in Yaounde-Cameroon. AB - INTRODUCTION: Many studies still show significant numbers of surgical patients contracting nosocomial infections each year globally with high morbidity and mortality. The aim of this study was to identify potential bacteria reservoirs that may be responsible for nosocomial infection in surgical services in the Yaounde University Teaching Hospital (YUTH) and the Central Hospital Yaounde (CHY). METHODS: A cross sectional descriptive study was conducted from June to August 2012. Air, water, and surface samples were collected from two surgical services and subjected to standard bacteriological analysis. RESULTS: A total of 143 surface samples were collected. Bacteria were isolated in all surfaces except from one trolley sample and a surgical cabinet sample. The predominant species in all services was coagulase negative Staphylococcus (CNS). The average number of colonies was 132. 82 CFU/25 cm(2). The bacteria isolated in the air were similar to those isolated from surfaces. From the 16 water samples cultured, an average of 50.93 CFU/100ml bacteria were isolated. The distribution of isolated species showed a predominance of Burkholderia cepacia. CONCLUSION: These results showed the importance of the hospital environment as a potential reservoir and source of nosocomial infections amongst surgical patient at YUTH and CHY, thus we suggest that Public health policy makers in Cameroon must define, publish guidelines and recommendations for monitoring environmental microbiota in health facilities. PMID- 26140068 TI - [Evaluation of results after treatment of cervical intraepithelial lesions by cryotherapy: a preliminary study at the University Hospital Centre in Yaounde: report of 21 cases]. PMID- 26140069 TI - [A rare complication of an internal jugular central venous catheter: pneumothorax, pneumo mediastinum and retro pneumoperitoneum and giant subcutaneous emphysema]. PMID- 26140070 TI - [Evolution of antibiotic resistance of Enterobacteriaceae isolated at the Douala General Hospital from 2005 to 2012]. PMID- 26140071 TI - [Volvulus of the gallbladder: report of an observation]. PMID- 26140072 TI - [Acute post surgical lung edema: a severe complication]. PMID- 26140073 TI - [Functional outcomes of cataract surgery by phacoemulsification with implantation in the posterior chamber: 300 cases in Bobo Dioulasso (Burkina Faso)]. PMID- 26140074 TI - Evaluation of hearing and cochlear function by audiometric testing in patients with hyperemesis gravidarum. AB - INTRODUCTION: The aim of this study was to investigate cochlear functions in patients with hyperemesis gravidarum (HG). METHODS: Twenty-nine HG patients (58 ears) and 31 healthy control subjects (62 ears) were included. Audiometry testings at 250 and 500 Hz and 1, 2, 4, 8, 10, 12, 14, 16 kHz were performed to the patients and controls. RESULTS: Mean age of patients with HG was 26,5 +/- 4,4 years and the mean age of control group was 28,0 +/- 4,2 years. At the time of the tests mean gestational age of the HG group and controls were 9 and 11 weeks respectively. No differences were observed between the groups in tympanic membrane status, or other otolaringological evaluations. No significant differences were observed in audiometric tests at any frequencies between the groups (p values for all > 0.05). CONCLUSION: There was not a difference between pregnant cases with HG and cases with normal pregnancy in terms of audimetric tests. Cochlear functions are not affected remarkably in women with HG. PMID- 26140075 TI - [Head and neck synovial sarcoma: a rare location: report of two cases]. PMID- 26140076 TI - Catching allergy by a simple questionnaire. AB - BACKGROUND: Identifying allergic rhinitis requires allergy testing, but the first line referral for rhinitis are usually primary care physicians (PCP), who are not familiar with such tests. The availability of easy and simple tests to be used by PCP to suggest allergy should be very useful. METHODS: The Respiratory Allergy Prediction (RAP) test, based on 9 questions and previously validated by a panel of experts, was evaluated in this study. RESULTS: An overall number of 401 patients (48.6% males, age range 14-62 years) with respiratory symptoms was included. Of them, 89 (22.2%) showed negative results to SPT, while 312 (77.8%) had at least one positive result to SPT. Cohen's kappa coefficient showed that all questions had an almost perfect excellent agreement between pre and post test. The algorithm of decision-tree growth Chi-squared Automatic Interaction Detector showed that answering yes to the question 4 (Your nasal/ocular complains do usually start or worsen during the spring?), 6 (Did you ever had cough or shortness of breath, even during exercise?) and 8 (Do you use nasal sprays frequently?) gave a probability to have a positive SPT of 85%. CONCLUSIONS: These findings show that RAP test can be proposed as an useful tool to be used by physician other than allergists when evaluating patients with rhinitis, suggesting the need of allergy testing. PMID- 26140077 TI - Genetic, familial and environmental correlates of asthma among early adolescents in Sri Lanka: a case control study. AB - BACKGROUND: Despite advances in management, the mortality and morbidity due to asthma are increasing globally. Identification of specific correlates in the local context is useful in disease management. The objective of this study was to estimate the prevalence and to describe selected correlates of asthma among12-14 year old school children in a district in Sri Lanka. METHOD: A school based cross sectional study was conducted using a self administered questionnaire. Multi staged stratified cluster sampling was used to select 42 classes in grades 7, 8 and 9. "Current asthma" (CA)(case) was defined as 'having Physician Diagnosed Asthma (PDA) and having had wheezing during the previous 12 months'. For each case, two healthy controls were selected from the same class to assess correlates. Information on correlates was collected by trained field midwives during home visits. Backward stepwise logistic regression model was used for analysis of correlates. Skin Prick Testing was carried out among asthmatics together with their healthy siblings using standard extracts of House Dust Mite (HDM), cockroach and Blomia. Ethical clearance was obtained from Ethical Review Committee, Faculty of Medicine, Colombo. RESULTS: Out of 1483 subjects participated, 753 were females (50.8%). The prevalence rates for current wheezing (CW), ever wheezing (EW), current asthma (CA), and physician diagnosed asthma (PDA) were 16.7%, 19.4%, 10.7% and 14.5% respectively. A total of 158 CA cases were identified. Information on correlates of asthma was collected for 145 CA cases (97.9%) and for 285 controls (96.6%). The unconfounded predictors of having CA among adolescents in the present sample were; only child in the family (OR = 4.2, 95% CI: 1.7-9.9); first born of the family (OR = 2.6 95% CI: 1.3-5.2); presence of allergic rhinitis (OR = 2.7, 95% CI: 1.6-4.6); family history of asthma (OR = 1.8, 95% CI: 1.1-3.2); family history of allergic rhinitis (OR = 1.9, 95% CI: 1.1-3.2); family history of eczema (OR = 1.8, 95% CI: 1.0-3.2). Higher risk of sensitization to cockroach, HDM and Blomia was seen among asthmatics compared to healthy siblings. CONCLUSION: A significant proportion of students reported to have asthma. Atopy and other genetic and environmental correlates should be considered as important correlates in asthma management among early adolescents in Sri Lanka. PMID- 26140079 TI - Liver ultrasound elastography: More than staging the disease. AB - Ultrasound elastography is perhaps the most important breakthrough in the evolution of ultrasonography in the last 15 years. Since transient elastography was introduced, many other methods have been developed and became more and more widely available. The value of ultrasound elastography in staging a chronic liver disease has been established by numerous studies. There have been many studies that have shown that using liver elastography it is possible to predict the presence of the complications of cirrhosis: portal hypertension, presence of esophageal varices (and even their risk of bleeding) and hepatocellular carcinoma. It has been shown that liver elastography can predict the progression of liver fibrosis and also the survival (hepatic events - free) of the patients with chronic liver diseases. These are the real quests of the clinicians, this is the ultimate scope of any medical investigation - to predict the outcome of a patient and to help making therapeutic decisions. I brought together only a small amount of the data that has already been written on this subject to support my affirmation that liver ultrasound elastography is more than a tool for staging the liver disease, but it is also comparable to a crystal ball which in the hands of a skilled clinician can reveal the future of the patient and can help to improve this future. PMID- 26140078 TI - The microbiome of the human lower airways: a next generation sequencing perspective. AB - For a long time, the human lower airways were considered a sterile environment where the presence of microorganisms, typically revealed by culturing, was interpreted as an abnormal health state. More recently, high-throughput sequencing-based studies have led to a shift in this perception towards the notion that even in healthy conditions the lower airways show either transient presence or even permanent colonization by microorganisms. However, challenges related to low biomass and contamination in samples still remain, and the composition, structure and dynamics of such putative microbial communities are unclear. Here, we review the evidence for the presence of microbial communities in the human lower airways, in healthy subjects and within the context of medical conditions of interest. We also provide an overview of the methodology pertinent to high-throughput sequencing studies, specifically those based on amplicon sequencing, including a discussion of good practices and common pitfalls. PMID- 26140080 TI - Treatment of ectopic varices with portal hypertension. AB - Ectopic varices are unusual with portal hypertension and can involve any site along the digestive tract outside the gastroesophageal region. Hemorrhage from ectopic varices generally are massive and life threatening. Diagnosis of ectopic varices is difficult and subsequent treatment is also difficult; the optimal treatment has not been established. Recently, interventional radiology and endoscopic treatments have been carried out successfully for hemorrhage from ectopic varices. PMID- 26140081 TI - Treatment of chronic hepatitis C in liver transplant candidates and recipients: Where do we stand? AB - The first generation direct antiviral agents (DAAs) highlighted substantial prognosis improvement among liver transplant (LT) candidates and recipients with recurrent hepatitis C virus (HCV) infection. During 2014, second generation DAAs are associated with high sustained virological response rates (> 95%), shortened duration courses and relatively few toxicities. In keeping with the currently available data, patients with decompensated cirrhosis awaiting LT is preferable to be treated with interferon-free, new generation DAAs, with or without ribavirin combinations. Although data about the safety of new DAAs combinations in this patient population are limited, sofosbuvir and daclatasvir pharmacokinetics do not appear to change significantly in moderate or severe liver impairment, while other new DAAs (simeprevir, asunaprevir) seem to be contraindicated in patients with severe liver impairment (Child-Pugh class C). On the other hand, sofosbuvir should not be given in patients with glomerular filtration rate <= 30 mL/min, but ongoing trials will clarify better this issue. With the objective that newer antiviral combinations will yield safer and more efficient manipulation of HCV recurrence post-transplant, the European Association for the Study of the Liver has recently updated its recommendations towards this direction. Nevertheless the new antivirals' high cost may be the biggest challenge to their implementation worldwide. PMID- 26140082 TI - Predictive factors associated with hepatitis C antiviral therapy response. AB - Hepatitis C virus (HCV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000s, dual therapy using a combination of pegylated interferon plus ribavirin (PR) became the standard of care for HCV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HCV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors (boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response (SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis C treatment has been rapidly changing with the development of new therapies and other developments. Currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs. PMID- 26140084 TI - Systematic review: Preventive and therapeutic applications of metformin in liver disease. AB - Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent for a broad spectrum of conditions, including liver disease and hepatic malignancies. In this systematic review, we critically analyze the literature behind the potential use of metformin across the spectrum of liver disease and malignancies. The PubMed and Ovid MEDLINE databases were searched from 2000 to March 2015, using a combination of relevant text words and MeSH terms: metformin and mammalian target of rapamycin, hepatitis B virus (HBV), hepatitis B virus (HCV), non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC) or cholangiocarcinoma. The search results were evaluated for pertinence to the issue of metformin in liver disease as well as for quality of study design. Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation. However, the literature thus far does not support any independent therapeutic role in NAFLD or HCV. Nonetheless, there is Level III evidence for a chemopreventive role in patients with diabetes and chronic liver disease, with decreased incidence of HCC and cholangiocarcinoma. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. In conclusion, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of chronic liver diseases, including NAFLD and HCV. However, there is good evidence for a chemopreventive role against HCC among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit. PMID- 26140083 TI - Guide for diagnosis and treatment of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is ranked as the 5(th) common type of cancer worldwide and is considered as the 3(rd) common reason for cancer-related deaths. HCC often occurs on top of a cirrhotic liver. The prognosis is determined by several factors; tumour extension, alpha-fetoprotein (AFP) concentration, histologic subtype of the tumour, degree of liver dysfunction, and the patient's performance status. HCC prognosis is strongly correlated with diagnostic delay. To date, no ideal screening modality has been developed. Analysis of recent studies showed that AFP assessment lacks adequate sensitivity and specificity for effective surveillance and diagnosis. Many tumour markers have been tested in clinical trials without progressing to routine use in clinical practice. Thus, surveillance is still based on ultrasound (US) examination every 6 mo. Imaging studies for diagnosis of HCC can fall into one of two main categories: routine non-invasive studies such as US, computed tomography (CT), and magnetic resonance imaging, and more specialized invasive techniques including CT during hepatic arteriography and CT arterial portography in addition to the conventional hepatic angiography. This article provides an overview and spotlight on the different diagnostic modalities and treatment options of HCC. PMID- 26140085 TI - Induced immunity against hepatitis B virus. AB - Prevention of hepatitis B virus (HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance of HBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination. PMID- 26140086 TI - Occult hepatitis B virus infection in Egypt. AB - The emerging evidence of the potentially clinical importance of occult hepatitis B virus (HBV) infection (OBI) increases the interest in this topic. OBI may impact in several clinical contexts, which include the possible transmission of the infection, the contribution to liver disease progression, the development of hepatocellular carcinoma, and the risk of reactivation. There are several articles that have published on OBI in Egyptian populations. A review of MEDLINE database was undertaken for relevant articles to clarify the epidemiology of OBI in Egypt. HBV genotype D is the only detectable genotype among Egyptian OBI patients. Higher rates of OBI reported among Egyptian chronic HCV, hemodialysis, children with malignant disorders, and cryptogenic liver disease patients. There is an evidence of OBI reactivation after treatment with chemotherapy. The available data suggested that screening for OBI must be a routine practice in these groups of patients. Further studies needed for better understand of the epidemiology of OBI among Egyptian young generations after the era of hepatitis B vaccination. PMID- 26140087 TI - Influence of gut bacteria on development and progression of non-alcoholic fatty liver disease. AB - The intestine of the human contains a dynamic population of microbes that have a symbiotic relationship with the host. In addition, there is an effect of the intestinal microbiota on metabolism and digestion. Non-alcoholic fatty liver disease (NAFLD) is a common cause worldwide of hepatic pathology and is thought to be the hepatic manifestation of the metabolic syndrome. In this review we examine the effect of the human microbiome on the components and pathogenesis of the metabolic syndrome. We are now on the threshold of therapeutic interventions on the human microbiome in order to effect human disease including NAFLD. PMID- 26140088 TI - Efficacy of tolvaptan in patients with refractory ascites in a clinical setting. AB - AIM: To elucidate the efficacies of tolvaptan (TLV) as a treatment for refractory ascites compared with conventional treatment. METHODS: We retrospectively enrolled 120 refractory ascites patients between January 1, 2009 and September 31, 2014. Sixty patients were treated with oral TLV at a starting dose of 3.75 mg/d in addition to sodium restriction (> 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-60 mg/d furosemide and 25-50 mg/d spironolactone) and 60 patients with large volume paracentesis in addition to sodium restriction (less than 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-120 mg/d furosemide and 25-150 mg/d spironolactone). Patient demographics and laboratory data, including liver function, were not matched due to the small number of patients. Continuous variables were analyzed by unpaired t test or paired t-test. Fisher's exact test was applied in cases comparing two nominal variables. We analyzed factors affecting clinical outcomes using receiver operating characteristic curves and multivariate regression analysis. We also used multivariate Cox's proportional hazard regression analysis to elucidate the risk factors that contributed to the increased incidence of ascites. RESULTS: TLV was effective in 38 (63.3%) patients. The best cut-off values for urine output and reduced urine osmolality as measures of refractory ascites improvement were > 1800 mL within the first 24 h and > 30%, respectively. Multivariate regression analysis indicated that > 25% reduced urine osmolality [odds ratio (OR) = 20.7; P < 0.01] and positive hepatitis C viral antibodies (OR = 5.93; P = 0.05) were positively correlated with an improvement of refractory ascites, while the total bilirubin level per 1.0 mg/dL (OR = 0.57; P = 0.02) was negatively correlated with improvement. In comparing the TLV group and controls, only the serum sodium level was significantly lower in the TLV group (133 mEq/L vs 136 mEq/L; P = 0.02). However, there were no significant differences in the other parameters between the two groups. The cumulative incidence rate was significantly higher in the control group with a median incidence time of 30 d in the TLV group and 20 d in the control group (P = 0.01). Cox hazard proportional multivariate analysis indicated that the use of TLV (OR = 0.58; P < 0.01), uncontrolled liver neoplasms (OR = 1.92; P < 0.01), total bilirubin level per 1.0 mg/dL (OR = 1.10; P < 0.01), and higher sodium level per 1.0 mEq/L (OR = 0.94; P < 0.01) were independent factors that contributed to incidence. CONCLUSION: Administration of TLV results in better control of refractory ascites and reduced the incidence of additional invasive procedures or hospitalization compared with conventional ascites treatments. PMID- 26140089 TI - Downstaging disease in patients with hepatocellular carcinoma outside up-to-seven criteria: Strategies using degradable starch microspheres transcatheter arterial chemo-embolization. AB - AIM: To evaluate the downstaging rates in hepatitis C virus-patients with hepatocellular carcinoma (HCC), treated with degradable starch microspheres transcatheter arterial chemoembolization (DSM-TACE), to reach new-Milan-criteria (nMC) for transplantation. METHODS: This study was approved by the Ethics Committee of our institution. From September 2013 to March 2014 eight patients (5 men and 3 women) with liver cirrhosis and multinodular HCC, that did not meet nMC at baseline, were enrolled in this study. Patients who received any other type of treatment such as termal ablation or percutaneous ethanol injection were excluded. DSM-TACE was performed in all patients using EmboCept((r)) S and doxorubicin. Baseline and follow-up computed tomography or magnetic resonance imaging was assessed measuring the longest enhancing axial dimension of each tumor according to the modified Response Evaluation Criteria In Solid Tumors measurements, and medical records were reviewed. RESULTS: DSM-TACE was successfully performed in all patients without major complication. We treated 35 lesions (mean 4.3 per patient). Six of eight patients (75%) had their HCC downstaged to meet nMC. Every patient whose disease was downstaged eventually underwent transplantation. The six patients who received transplant were still living at the time of this writing, without recurrence of HCC. Baseline age (P = 0.25), Model for End-stage Liver Disease score (P = 0. 77), and alpha-fetoprotein level (P = 1.00) were similar between patients with and without downstaged HCC. CONCLUSION: DSM-TACE represents a safely and effective treatment option with similar safety and efficacy of conventional chemoembolization and could be successfully performed also for downstaging disease in patients without nMC, allowing them to reach liver transplantation. PMID- 26140090 TI - (1)H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy. AB - AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics. METHODS: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using (1)H - nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients (FID's) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three groups. RESULTS: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate (0.23 +/- 0.02 vs 0.05 +/- 0.00, P < 0.01), and b-hydroxybutarate (0.58 +/- 0.14 vs 0.08 +/- 0.00, P < 0.01), lower concentrations of glutamine (0.44 +/- 0.08 vs 0.63 +/- 0.03, P < 0.05), histidine (0.16 +/- 0.01 vs 0.36 +/- 0.04, P < 0.01) and arginine (0.08 +/ 0.01 vs 0.14 +/- 0.02, P < 0.03) and higher concentrations of glutamate (1.36 +/ 0.25 vs 0.58 +/- 0.04, P < 0.01), lactate (1.53 +/- 0.11 vs 0.42 +/- 0.05, P < 0.01), pyruvate (0.11 +/- 0.02 vs 0.03 +/- 0.00, P < 0.01) threonine (0.39 +/- 0.02 vs 0.08 +/- 0.01, P < 0.01) and aspartate (0.37 +/- 0.03 vs 0.03 +/- 0.01). A five metabolite signature by stepwise discriminant analysis could separate between controls and cirrhotic patients with an accuracy of 98%. In patients with encephalopathy we observed further derangement of ketone body metabolism, impaired production of glycerol and myoinositol, reversal of Fischer's ratio and impaired glutamine production as demonstrated by lower b-hydroxybutyrate (0.58 +/ 0.14 vs 0.16 +/- 0.02, P < 0.0002), higher acetoacetate (0.23 +/- 0.02 vs 0.41 +/- 0.16, P < 0.05), leucine (0.33 +/- 0.02 vs 0.49 +/- 0.05, P < 0.005) and isoleucine (0.12 +/- 0.02 vs 0.27 +/- 0.02, P < 0.0004) and lower glutamine (0.44 +/- 0.08 vs 0.36 +/- 0.04, P < 0.013), glycerol (0.53 +/- 0.03 vs 0.19 +/- 0.02, P < 0.000) and myoinositol (0.36 +/- 0.04 vs 0.18 +/- 0.02, P < 0.010) concentrations. A four metabolite signature by stepwise discriminant analysis could separate between encephalopathic and cirrhotic patients with an accuracy of 87%. CONCLUSION: Patients with cirrhosis and patients with hepatic encephalopathy exhibit distinct metabolic abnormalities and the use of metabonomics can select biomarkers for these diseases. PMID- 26140092 TI - Severe immune thrombocytopenia after peg-interferon-alpha2a, ribavirin and telaprevir treatment completion: A case report and systematic review of literature. AB - Mild to moderate autoimmune thrombocytopenia (AITP) is a common finding in patients receiving interferon-based antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus (HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferon-based antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment (i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferon-based treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but also after discontinuation. PMID- 26140093 TI - Non-alcoholic fatty liver disease and beneficial effects of dietary supplements. AB - I read with great interest the review published by Eslamparast et al, on the dietary supplements with hepato-protective properties, and their proposed mechanisms to protect against non-alcoholic fatty liver disease. In this way, recently, our study group reported the efficacy of the Mediterranean diet associated to an antioxidant complex, to improve in overweight patients not only anthropometric parameters, but also insulin-resistance, lipid serum levels, and intra-hepatic fat accumulation. PMID- 26140091 TI - Hepatocellular carcinoma in Asia: Prevention strategy and planning. AB - AIM: To review all of epidemiological and etiological aspects of hepatocellular carcinoma (HCC) and examined the prevention of this disease in Asia. METHODS: We conducted a systematic review according to the PRISMA guidelines. We were chosen articles that published previously, from PubMed (MEDLINE), the Cochrane database and Scopus. The key words used in this research were as follows: HCC in Asia and the way of prevention of this disease, with no language limitations. We selected those papers published before 2014 that we considered to be most important and appropriate. All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed. RESULTS: More than 70% of all new cases of liver cancer were diagnosed in Asia, a region that 75% of all those chronically infected with hepatitis B virus (HBV) in the world. Chronic HBV infection is the main cause of HCC in Asia, where the virus is endemic and vertical transmission is common. Japan, Saudi Arabia, Egypt and Pakistan are exception because of high prevalence of HCV infection in these regions. The prevalence of this cancer is high in Eastern and South-Eastern Asia, But Middle Eastern countries are characterized as moderate prevalence rate of HCC region and Central Asia and some part of Middle Eastern countries are known as low prevalence rate of HCC. In addition of HBV and HCV the other factors such as aflatoxin, alcohol, obesity, diabetes and non-alcoholic fatty liver disease (NAFLD) might be responsible for a low prevalence of HCC in Asian countries. Currently available HCC therapies, chemotherapy, surgical are inefficient, mainly due to usually late diagnosis and high recurrence rates after surgical resection, and usually end with treatment failure. Liver transplantation also remains as a difficult strategy in patients with HCC. Thus prevention of HCC by treating and prevention HBV and HCV infection, the major causative agents of HCC, and the other risk factors such as aflatoxin, alcohol, obesity, diabetes and NAFLD is of a great medical importance. CONCLUSION: The main challenge which still present in Asia, is the high prevalence of chronic hepatitis. So, prevention of HBV and HCV is the key strategy to reduce the incidence of HCC in Asia. PMID- 26140094 TI - Gastrointestinal endoscopy biopsy derived proteomic patterns predict indeterminate colitis into ulcerative colitis and Crohn's colitis. AB - Patients with indeterminate colitis (IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microscopic visual predict precision of eventual ulcerative colitis (UC) or Crohn's colitis (CC) which is not offered in 15%-30% of inflammatory bowel disease (IBD) patients even after a combined state-of-the-art classification system of clinical, visual endoscopic, radiologic and histologic examination. These figures have not changed over the past 3 decades despite the introduction of newer diagnostic modalities. The patient outcomes after restorative proctocolectomy and ileal pouch-anal anastomosis may be painstaking if IC turns into CC. Our approach is aiming at developing a single sensitive and absolute accurate diagnostic test tool during the first clinic visit through endoscopic biopsy derived proteomic patterns. Matrix-assisted-laser desorption/ionization mass spectrometry (MS) and/or imaging MS technologies permit a histology-directed cellular test of endoscopy biopsy which identifies phenotype specific proteins, as biomarker that would assist clinicians more accurately delineate IC as being either a UC or CC or a non-IBD condition. These novel studies are underway on larger cohorts and are highly innovative with significances in differentiating a UC from CC in patients with IC and could lend mechanistic insights into IBD pathogenesis. PMID- 26140095 TI - Advances in endoscopic retrograde cholangiopancreatography for the treatment of cholangiocarcinoma. AB - Cholangiocarcinoma (CCA) is a malignancy of the bile ducts that carries high morbidity and mortality. Patients with CCA typically present with obstructive jaundice, and associated complications of CCA include cholangitis and biliary sepsis. Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable treatment modality for patients with CCA, as it enables internal drainage of blocked bile ducts and hepatic segments by using plastic or metal stents. While there remains debate as to if bilateral (or multi-segmental) hepatic drainage is required and/or superior to unilateral drainage, the underlying tenant of draining any persistently opacified bile ducts is paramount to good ERCP practice and good clinical outcomes. Endoscopic therapy for malignant biliary strictures from CCA has advanced to include ablative therapies via ERCP-directed photodynamic therapy (PDT) or radiofrequency ablation (RFA). While ERCP techniques cannot cure CCA, advancements in the field of ERCP have enabled us to improve upon the quality of life of patients with inoperable and incurable disease. ERCP-directed PDT has been used in lieu of brachytherapy to provide neoadjuvant local tumor control in patients with CCA who are awaiting liver transplantation. Lastly, mounting evidence suggests that palliative ERCP-directed PDT, and probably ERCP-directed RFA as well, offer a survival advantage to patients with this difficult-to-treat malignancy. PMID- 26140096 TI - Role of endoscopic ultrasonography in the loco-regional staging of patients with rectal cancer. AB - The prognosis of rectal cancer (RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC (LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy (NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound (EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor (T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery. PMID- 26140097 TI - Endotherapy of leaks and fistula. AB - Perforations, leaks and fistula involving gastrointestinal (GI) tract are increasing encountered in clinical practice. There is a changing paradigm for their management with surgical approach being replaced by conservative approach including endoscopic therapy. Clips (through the scope and over the scope) and covered stent are front runners for endotherapy for GI leaks and fistula. Over the scope clips introduced recently, can treat larger defects compared to through the scope clips. Covered stents are suited for larger defects and those associated with luminal narrowing. However cervical esophagus, gastro-esophageal junction, stomach and right colonic lesions may be better for clip therapy rather than stenting. Recent developments in this field include use of endovac therapy which consists of a sponge with suction device, biodegradable stent, use of fibrin glue and some endo-suturing device. Conservative therapy with no surgical or endoscopic intervention, may be suitable for a small subset of patients. An algorithm based on location, size of defect, associated stricture, infection and available expertise needs to be developed to reduce the mortality and morbidity of this difficult clinical problem. PMID- 26140098 TI - Current status of laparoendoscopic rendezvous in the treatment of cholelithiasis with concomitant choledocholithiasis. AB - The current evidence in favor of the laparoendoscopic rendezvous is promising and demonstrates the main advantages of this technique in regard to shorter hospital stay and selective cannulation of the common bile duct (CBD), avoiding thus the inadvertent cannulation of the pancreatic duct. In addition, in the rendezvous technique the contrast medium is not injected retrogradely as during the traditional endoscopic retrograde cholangiopancreatography (ERCP), when the medium accidentally could be injected under pressure into the pancreatic duct. The RV technique minimizes that risk. Both these main advantages of the RV technique over the classic ERCP, are related with a significant lower incidence of hyperamylasemia and post-ERCP pancreatitis, compared with the traditional two stage procedure. Choledocholithiasis is present in 10% to 15% of patients undergoing cholecystectomy. To date, the ideal management of CBD stones remains controversial. Prospective randomized trials have shown that laparoscopic management of the CBD stones, as a single stage procedure, is the most efficient and cost effective method of treatment. Laparoendoscopic rendezvous has been proposed as an alternative single stage approach. Several studies have shown the effective use of this technique in the treatment of CBD stones by improving patient compliance and clinical results including shorter hospital stay, higher success rate and less cost. The current evidence about the use of this technique presented in this review article is promising and demonstrates the main advantages of the procedure. PMID- 26140099 TI - Endoscopic mucosal resection and endoscopic submucosal dissection in the treatment of sporadic nonampullary duodenal adenomatous polyps. AB - Although uncommon, sporadic nonampullary duodenal adenomas have a growing detection due to the widespread of endoscopy. Endoscopic therapy is being increasingly used for these lesions, since surgery, considered the standard treatment, carries significant morbidity and mortality. However, the knowledge about its risks and benefits is limited, which contributes to the current absence of standardized recommendations. This review aims to discuss the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in the treatment of these lesions. A literature review was performed, using the Pubmed database with the query: "(duodenum or duodenal) (endoscopy or endoscopic) adenoma resection", in the human species and in English. Of the 189 retrieved articles, and after reading their abstracts, 19 were selected due to their scientific interest. The analysis of their references, led to the inclusion of 23 more articles for their relevance in this subject. The increased use of EMR in the duodenum has shown good results with complete resection rates exceeding 80% and low complication risk (delayed bleeding in less than 12% of the procedures). Although rarely used in the duodenum, ESD achieves close to 100% complete resection rates, but is associated with perforation and bleeding risk in up to one third of the cases. Even though literature is insufficient to draw definitive conclusions, studies suggest that EMR and ESD are valid options for the treatment of nonampullary adenomas. Thus, strategies to improve these techniques, and consequently increase the effectiveness and safety of the resection of these lesions, should be developed. PMID- 26140100 TI - Feasibility and safety of endoscopic cryoablation at the duodenal papilla: Porcine model. AB - AIM: To assess the feasibility and safety of liquid nitrogen spray cryoablation at the duodenal papilla in a porcine model. METHODS: This prospective study protocol was approved by the University of Florida Institutional Animal Care and Use Committee. Six pigs underwent liquid nitrogen spray cryotherapy at the duodenal papilla. Freeze time of 20-s was applied per cycle (4 cycles/session). Survival animals (n = 4) were monitored for adverse events. Hemoglobin, white blood count, liver tests, and lipase were obtained at baseline and post treatment. EGD was performed on day#7 to evaluate the papilla and for histology. All animals were euthanized and necropsy was performed at the end of the one-week survival period. Feasibility was defined as successful placement of the decompression tube in the duodenum, followed by delivery of spray cryotherapy to the duodenal papilla. Safety was determined by monitoring post-treatment blood tests and clinical course. Treatment effect was defined as endoscopic and histologic changes after cryotherapy. This was established by comparing endoscopic and histologic findings from mucosal biopsies prior to cryotherapy and on post-operative day (POD)#7. Full-thickness specimen was obtained post-mortem to assess depth of injury. RESULTS: Spray cryotherapy was feasible and successfully performed in all 6/6 (100%) animals. Cryospray with liquid nitrogen (four 20-s freeze-thaw cycles) at the duodenal papilla resulted in white frost formation at and around the target region. The mean procedural time was 54.5 min (range 50-58 min). All six animals studied had stable blood pressure, heart rate, and pulse oximetry measurements during the procedure. There were no significant intra-procedural adverse events. There were no significant differences in hemoglobin, white cell count, liver tests or lipase from baseline to post cryotherapy. Survival animals were monitored daily post-operatively without any clinical ill effects from the cryotherapy. There was no bleeding, infection, or perforation on necropsy. Endoscopic on POD#7 showed edema and ulceration at the duodenal papilla. On histology, there was loss of crypt architecture with moderate to severe necrosis and acute mixed inflammatory infiltration in each specimen following cryotherapy. The extent of cryogen-induced tissue necrosis (depth of injury) was limited to the mucosa on full-thickness specimen evaluation. CONCLUSION: Endoscopic liquid nitrogen spray cryotherapy is feasible and safe for ablation at the duodenal papilla in a porcine model. PMID- 26140101 TI - Obtaining research biopsies during pediatric colonoscopy: Safety and adverse events. AB - AIM: To investigate the safety profile of acquiring additional intestinal biopsies for research purposes in children undergoing a medically indicated colonoscopy. METHODS: A retrospective review of 122 pediatric patients who underwent colonoscopy over a 9 mo time period was completed. 38/122 participants consented to a research study in which 4 additional biopsies were obtained, in addition to routine biopsies. The outcomes after colonoscopy were measured in the research participants, and compared to 84 control participants who did not consent for the study. Groups were compared with regard to number of biopsies obtained, underlying diagnosis, and both serious and minor adverse outcomes. Data was collected including: age, gender, race, indication, diagnosis, number of biopsies obtained per case and post procedure adverse events. Medical records were reviewed and a questionnaire was completed by each of the ten gastroenterologists who performed procedures during the study. Physicians were asked about individual patient outcomes to ensure that all adverse events, such as perforation, excessive bleeding, infection, and minor gastrointestinal outcomes, were captured and included. RESULTS: The research group had more biopsies obtained (mean = 13.58 +/- 4.21) compared to controls (mean = 9.33 +/- 4.40), P <= 0.0001, however there was no difference in adverse events. Serious outcomes, defined as perforation, bleeding and infection, did not occur, in either group. As such, the relationship between serious adverse events and number of biopsies obtained was not determined. Minor gastrointestinal outcomes, such as abdominal pain, diarrhea or vomiting, were reported in 21 patients (8 research participants and 13 control participants) however the incidence of minor gastrointestinal outcomes between the two groups did not vary significantly, P = 0.45. Additionally, the mean number of biopsies obtained in patients who had a minor outcome (mean = 12.1 +/- 0.77), compared to those with no adverse outcome (mean = 10.34 +/- 0.5), revealed no statistical difference between the groups (P = 0.12), suggesting that number of biopsies is not associated with incidence of minor adverse events. CONCLUSION: Patients participating in research requiring acquisition of additional biopsies for research purposes alone, are not at an increased risk of adverse outcomes. PMID- 26140102 TI - Endoscopic features of early-stage signet-ring-cell carcinoma of the stomach. AB - AIM: To identify the features of early signet ring cell gastric carcinoma using magnification endoscopy with narrow band imaging (NBI). METHODS: A retrospective review was conducted of 12 cases of early signet ring cell gastric carcinoma who underwent treatment in a single institution between January 2009 and April 2013. All patients had magnification endoscopy with NBI and indigo carmine contrast to closely examine the mucosal architecture, including the microvasculature and arrangement of gastric pits. Histologic examination of the final endoscopic submucosal dissection or gastrectomy specimen was performed and compared with the endoscopic findings to identify patterns specific to signet ring cell carcinoma. RESULTS: Twelve patients with early signet ring cell gastric carcinoma were identified; 75% were male, and average age was 61 years. Most of the lesions were stage T1a (83%), while the remainder were T1b (17%). The mean lesion size was 1.4 cm(2). On standard endoscopy, all 12 patients had a pale, flat lesion without any evidence of mucosal abnormality such as ulceration, elevation, or depression. On magnification endoscopy with NBI, all of the patients had irregularities in the glands and microvasculature consistent with early gastric cancer. In addition, all 12 patients exhibited the "stretch sign", an elongation or expansion of the architectural structure. Histologic examination of the resected specimens demonstrated an expanded and edematous mucosal layer infiltrated with tumor cells. CONCLUSION: The "stretch sign" appears to be specific for signet ring cell carcinoma and may aid in the early diagnosis and treatment of this aggressive pathology. PMID- 26140104 TI - JGME Welcomes Deputy Editors. PMID- 26140103 TI - Management of liver transplantation biliary stricture: Results from a tertiary hospital. AB - AIM: To review results of endoscopic treatment for anastomotic biliary strictures after orthotopic liver transplantation (OLT) during an 8-year period. METHODS: This is a retrospective review of all endoscopic retrograde cholangiopancreatographys (ERCPs) performed between May 2006 and June 2014 in deceased OLT recipients with anastomotic stricture at a tertiary care hospital. Patients were divided into 2 groups, according to the type of stent used (multiple plastic or covered self-expandable metal stents), which was chose on a case-by-case basis and their characteristics. The primary outcome was anastomotic stricture resolution rate determined if there was no more than a minimum waist at cholangiography and a 10 mm balloon could easily pass through the anastomosis with no need for further intervention after final stent removal. Secondary outcomes were technical success rate, number or ERCPs required per patient, number of stents placed, stent indwelling, stricture recurrence rate and therapy for recurrent anastomotic biliary stricture (AS). Stricture recurrence was defined as clinical laboratorial and/or imaging evidence of obstruction at the anastomosis level, after it was considered completely treated, requiring subsequent interventional procedure. RESULTS: A total of 195 post-OLT patients were assessed for eligibility. One hundred and sixty-four (164) patients were diagnosed with anastomotic biliary stricture. ERCP was successfully performed in 157/164 (95.7%) patients with AS, that were treated with either multiple plastic (n = 109) or metallic billiary stents (n = 48). Mean treatment duration, number of procedures and stents required were lower in the metal stent group. Acute pancreatitis was the most common procedure related complication, occurring in 17.1% in the covered self-expandable metal stents (cSEMS) and 4.1% in the multiple plastic stent (MPS) group. Migration was the most frequent stent related complication, observed in 4.3% and 5.5% (cSEMS and MPS respectively). Stricture resolution was achieved in 86.8% in the cSEMS group and in 91% in MPS group. Stricture recurrence after a median follow up of 20 mo was observed in 10 (30.3%) patients in the cSEMS and 7 (7.7%) in the plastic stent group, a statistically significant difference (P = 0.0017). Successful stricture resolution after secondary treatment was achieved in 66.6% and 62.5% of patients respectively in the cSEMS and plastic stents groups. CONCLUSION: Multiple plastic stents are currently the first treatment option for AS in patients with duct-to-duct anastomosis. cSEMS was associated with increased pancreatitis risk and higher recurrence rate. PMID- 26140105 TI - Applying Clinical Research Skills to Conduct Education Research: Important Recommendations for Success. PMID- 26140106 TI - Five Tips for a Successful Submission on Simulation-Based Medical Education. PMID- 26140107 TI - Think Games on the Fly, Not Gamify: Issues in Game-Based Learning Research. PMID- 26140108 TI - Becoming a Doctor: One Physician's Journey Beyond Competence. PMID- 26140109 TI - Global Health Telemedicine Conferences: The System We Save May Be Our Own. PMID- 26140110 TI - A Compass for Scholarship: The Scholarly Activity Expectations Rubric. PMID- 26140111 TI - X + Y Scheduling Models for Internal Medicine Residency Programs-A Look Back and a Look Forward. PMID- 26140112 TI - Effects of Postgraduate Medical Education "Boot Camps" on Clinical Skills, Knowledge, and Confidence: A Meta-Analysis. AB - BACKGROUND: Throughout their medical education, learners face multiple transition periods associated with increased demands, producing stress and concern about the adequacy of their skills for their new role. OBJECTIVE: We evaluated the effectiveness of boot camps in improving clinical skills, knowledge, and confidence during transitions into postgraduate or discipline-specific residency programs. METHODS: Boot camps are in-training courses combining simulation-based practice with other educational methods to enhance learning and preparation for individuals entering new clinical roles. We performed a search of MEDLINE, CINAHL, PsycINFO, EMBASE, and ERIC using boot camp and comparable search terms. Inclusion criteria included studies that reported on medical education boot camps, involved learners entering new clinical roles in North American programs, and reported empirical data on the effectiveness of boot camps to improve clinical skills, knowledge, and/or confidence. A random effects model meta analysis was performed to combined mean effect size differences (Cohen's d) across studies based on pretest/posttest or comparison group analyses. RESULTS: The search returned 1096 articles, 15 of which met all inclusion criteria. Combined effect size estimates showed learners who completed boot camp courses had significantly "large" improvements in clinical skills (d = 1.78; 95% CI 1.33-2.22; P < .001), knowledge (d = 2.08; 95% CI 1.20-2.96; P < .001), and confidence (d = 1.89; 95% CI 1.63-2.15; P < .001). CONCLUSIONS: Boot camps were shown as an effective educational strategy to improve learners' clinical skills, knowledge, and confidence. Focus on pretest/posttest research designs limits the strength of these findings. PMID- 26140113 TI - Effects of Fatigue on Driving Safety: A Comparison of Brake Reaction Times in Night Float and Postcall Physicians in Training. AB - BACKGROUND: Concerns about duty hour and resident safety have fostered discussion about postshift fatigue and driving impairment. OBJECTIVE: We assessed how converting to a night float schedule for overnight coverage affected driving safety for trainees. METHODS: Brake reaction times were measured for internal medicine and orthopaedic surgery resident volunteers after a traditional 28-hour call shift and after a night float shift. We conducted matched paired t tests of preshift and postshift reaction time means. Participants also completed the Epworth Sleepiness Scale pre- and postshift. RESULTS: From June to July 2013, we enrolled 58 interns and residents (28 orthopaedic surgery, 30 internal medicine). We included 24 (41%) trainees on night float rotations and 34 (59%) trainees on traditional 28-hour call shifts. For all residents on night float rotations, there was no significant difference pre- and postshift. An increase in reaction times was noted among trainees on 28-hour call rotations. This included no effect on reaction times for internal medicine trainees pre- and postshift, and an increase in reaction times for orthopaedic trainees. For both night float and traditional call groups, there were significant increases in the Epworth Sleepiness Scale. CONCLUSIONS: Trainees on traditional 28-hour call rotations had significantly worse postshift brake reaction times, whereas trainees on night float rotations had no difference. Orthopaedic trainees had significant differences in brake reaction times after a traditional call shift. PMID- 26140114 TI - Hospitalized Patients' Perceptions of Resident Fatigue, Duty Hours, and Continuity of Care. AB - BACKGROUND: Physicians' perceptions of duty hour regulations have been closely examined, yet patient opinions have been largely unstudied to date. OBJECTIVE: We studied patient perceptions of residency duty hours, fatigue, and continuity of care following implementation of the Accreditation Council for Graduate Medical Education 2011 Common Program Requirements. METHODS: A cross-sectional survey was administered between June and August 2013 to inpatients at a large academic medical center and an affiliated community hospital. Adult inpatients on teaching medical and surgical services were eligible for inclusion in the study. RESULTS: Survey response rate was 71.3% (513 of 720). Most respondents (57.1%, 293 of 513) believed residents should not be assigned to shifts longer than 12 hours, and nearly half (49.7%, 255 of 513) wanted to be notified if a resident caring for them had worked longer than 12 hours. Most patients (63.2%, 324 of 513) believed medical errors commonly occurred because of fatigue, and fewer (37.4%, 192 of 513; odds ratio, 0.56; P < .01) believed medical errors commonly occurred as a result of transfers of care. Given the choice between a familiar physician who "may be tired from a long shift" or a "fresh" physician who had received sign out, more patients chose the fresh but unfamiliar physician (57.1% [293 of 513] versus 42.7% [219 of 513], P < .01). CONCLUSIONS: In a survey about physician attributes relevant to medical errors and patient safety, adult inpatients in a large and diverse sample reported greater concern about fatigue and working hours than about continuity of care. PMID- 26140115 TI - An Evidence-Based Medicine Curriculum Improves General Surgery Residents' Standardized Test Scores in Research and Statistics. AB - BACKGROUND: The application of evidence-based medicine to patient care requires unique skills of the physician. Advancing residents' abilities to accurately evaluate the quality of evidence is built on understanding of fundamental research concepts. The American Board of Surgery In-Training Examination (ABSITE) provides a relevant measure of surgical residents' knowledge of research design and statistics. OBJECTIVE: We implemented a research education curriculum in an independent academic medical center general residency program, and assessed the effect on ABSITE scores. METHODS: The curriculum consisted of five 1-hour monthly research and statistics lectures. The lectures were presented before the 2012 and 2013 examinations. Forty residents completing ABSITE examinations from 2007 to 2013 were included in the study. Two investigators independently identified research-related item topics from examination summary reports. Correct and incorrect responses were compared precurriculum and postcurriculum. Regression models were calculated to estimate improvement in postcurriculum scores, adjusted for individuals' scores over time and postgraduate year level. RESULTS: Residents demonstrated significant improvement in postcurriculum examination scores for research and statistics items. Correct responses increased 27% (P < .001). Residents were 5 times more likely to achieve a perfect score on research and statistics items postcurriculum (P < .001). CONCLUSIONS: Residents at all levels demonstrated improved research and statistics scores after receiving the curriculum. Because the ABSITE includes a wide spectrum of research topics, sustained improvements suggest a genuine level of understanding that will promote lifelong evaluation and clinical application of the surgical literature. PMID- 26140116 TI - Burnout and Physical Activity in Minnesota Internal Medicine Resident Physicians. AB - BACKGROUND: Regular physical activity plays an important role in the amelioration of several mental health disorders; however, its relationship with burnout has not yet been clarified. OBJECTIVE: To determine the association between achievement of national physical activity guidelines and burnout in internal medicine resident physicians. METHODS: A Web-based survey of internal medicine resident physicians at the University of Minnesota and Hennepin County Medical Center was conducted from September to October 2012. Survey measures included the Maslach Burnout Inventory-Human Services Survey and the International Physical Activity Questionnaire. RESULTS: Of 149 eligible residents, 76 (51.0%) completed surveys, which were used in the analysis. Burnout prevalence, determined by the Maslach Burnout Inventory, was 53.9% (41 of 76). Prevalence of failure to achieve US Department of Health and Human Services physical activity guidelines was 40.8% (31 of 76), and 78.9% (60 of 76) of residents reported that their level of physical activity has decreased since they began medical training. Residents who were able to meet physical activity guidelines were less likely to be burned out than their fellow residents (OR, 0.38, 95% CI 0.147-0.99). CONCLUSIONS: Among internal medicine resident physicians, achievement of national physical activity guidelines appears to be inversely associated with burnout. Given the high national prevalence of burnout and inactivity, additional investigation of this relationship appears warranted. PMID- 26140117 TI - Comparing Resident Self-Report to Chart Audits for Quality Improvement Projects: Accurate Reflection or Cherry-Picking? AB - BACKGROUND: Resident engagement in quality improvement is a requirement for graduate medical education, but the optimal means of instruction and evaluation of resident progress remain unknown. OBJECTIVE: To determine the accuracy of self reported chart audits in measuring resident adherence to primary care clinical practice guidelines. METHODS: During the 2010-2011 academic year, second- and third-year internal medicine residents at a single, university hospital-based program performed chart audits on 10 patients from their primary care clinic to determine adherence to 16 US Preventive Services Task Force primary care guidelines. We compared residents' responses to independent audits of randomly selected patient charts by a single external reviewer. RESULTS: Self-reported data were collected by 18 second-year and 15 third-year residents for 330 patients. Independently, 70 patient charts were randomly selected for review by an external auditor. Overall guideline compliance was significantly higher on self-reported audits compared to external audits (82% versus 68%, P < .001). Of 16 guidelines, external audits found significantly lower rates of adherence for 5 (tetanus vaccination, osteoporosis screening, colon cancer screening, cholesterol screening, and obesity screening). Chlamydia screening was more common in audited charts than in self-reported data. Although third-year residents self-reported higher guideline adherence than second-year residents (86% versus 78%, P < .001), external audits for third-year residents found lower overall adherence (64% versus 72%, P = .040). CONCLUSIONS: Residents' self-reported chart audits may significantly overestimate guideline adherence. Increased supervision and independent review appear necessary to accurately evaluate resident performance. PMID- 26140118 TI - A Faculty Development Program to Reduce Rater Error on Milestone-Based Assessments. AB - BACKGROUND: Rater errors, such as halo/reverse halo, range restriction, and leniency errors, are frequently cited as threats to the validity of resident assessment by faculty. OBJECTIVE: We studied whether participation in faculty development on the use of a new Milestone-based assessment tool reduced rater error for participants compared to individuals who did not participate. METHODS: We reviewed evaluations of resident Milestones completed by faculty at the end of rotations between July 2012 and June 2013. The 2 Milestones in each competency with the greatest number of ratings were selected for analysis. RESULTS: A total of 412 evaluations were analyzed, including 217 completed by faculty who participated in the development activity, and 240 completed by nonparticipant faculty. All evaluations that contained identical scores for all Milestones (16%) were completed by nonparticipant faculty (chi(2) = 37.498, P < .001). Faculty who had participated in development assigned a wider range of scores and lower minimum scores to residents, and provided the highest ratings for residents less frequently (P < .001) than nonparticipants. CONCLUSIONS: Faculty who participated in education about the Milestones demonstrated significantly less halo, range restriction, and leniency errors than faculty members who did not participate. These findings support a recommendation to develop a cadre of "core faculty" by training them in the use of Milestone assessment tools, and making them responsible for a significant portion of resident assessments. PMID- 26140119 TI - Financing Residency Training Redesign. AB - BACKGROUND: Redesign in the health care delivery system creates a need to reorganize resident education. How residency programs fund these redesign efforts is not known. METHODS: Family medicine residency program directors participating in the Preparing Personal Physicians for Practice (P(4)) project were surveyed between 2006 and 2011 on revenues and expenses associated with training redesign. RESULTS: A total of 6 university-based programs in the study collectively received $5,240,516 over the entire study period, compared with $4,718,943 received by 8 community-based programs. Most of the funding for both settings came from grants, which accounted for 57.8% and 86.9% of funding for each setting, respectively. Department revenue represented 3.4% of university-based support and 13.1% of community-based support. The total average revenue (all years combined) per program for university-based programs was just under $875,000, and the average was nearly $590,000 for community programs. The vast majority of funds were dedicated to salary support (64.8% in university settings versus 79.3% in community-based settings). Based on the estimated ratio of new funding relative to the annual costs of training using national data for a 3-year program with 7 residents per year, training redesign added 3% to budgets for university-based programs and about 2% to budgets for community-based programs. CONCLUSIONS: Residencies undergoing training redesign used a variety of approaches to fund these changes. The costs of innovations marginally increased the estimated costs of training. Federal and local funding sources were most common, and costs were primarily salary related. More research is needed on the costs of transforming residency training. PMID- 26140120 TI - What Makes a Great Resident Teacher? A Multicenter Survey of Medical Students Attending an Internal Medicine Conference. AB - BACKGROUND: Residents have a critical role in the education of medical students and have a unique teaching relationship because of their close proximity in professional development and opportunities for direct supervision. Although there is emerging literature on ways to prepare residents to be effective teachers, there is a paucity of data on what medical students believe are the attributes of successful resident teachers. OBJECTIVE: We sought to define the qualities and teaching techniques that learners interested in internal medicine value in resident teachers. METHODS: We created and administered a resident-as-teacher traits survey to senior medical students from 6 medical schools attending a resident-facilitated clinical conference at McMaster University. The survey collected data on student preferences of techniques employed by resident teachers and qualities of a successful resident teacher. RESULTS: Of 90 student participants, 80 (89%) responded. Respondents found the use of clinical examples (78%, 62 of 80) and repetition of core concepts (71%, 58 of 80) highly useful. In contrast, most respondents did not perceive giving feedback to residents, or receiving feedback from residents, was useful to their learning. With respect to resident qualities, respondents felt that a strong knowledge base (80%, 64 of 80) and tailoring teaching to the learner's level (83%, 66 of 80) was highly important. In contrast, high expectations on the part of resident supervisors were not valued. CONCLUSIONS: This multicenter survey provides insight into the perceptions of medical students interested in internal medicine on the techniques and qualities that characterize successful resident teachers. The findings may be useful in the future development of resident-as-teacher curricula. PMID- 26140121 TI - Survey of Residents' Attitudes and Awareness Toward Teaching and Student Feedback. AB - BACKGROUND: Teaching medical students is an important component of residency; however, little is known about student feedback regarding resident teaching skills. OBJECTIVE: We sought to explore resident awareness of medical student feedback mechanisms and how feedback is obtained, and also identified attitudes about teaching more commonly found in residents who seek feedback. METHODS: We surveyed all resident physicians at a university-affiliated academic health center about awareness of student feedback regarding their teaching abilities, and their attitudes related to teaching that may impact whether residents seek feedback. RESULTS: Of 605 residents, 335 (55%) responded, with 72% (242 of 335) noting they did not formally review student feedback of their teaching with their advisor during regularly scheduled meetings, 42% (140 of 332) reporting they did not know of any formal feedback mechanisms, and 28.4% (95 of 334) reporting they had not received feedback from students in any format. Although only a quarter of residents solicit feedback always or often, more than half would like feedback always or often. Reported barriers to feedback included student apprehension, time constraints, and lack of a formal system. A majority of residents had positive attitudes toward teaching and felt that student feedback would help teaching ability and medical proficiency. CONCLUSIONS: A large percentage of residents at 1 teaching institution reported not receiving feedback from students on their teaching abilities. Residents who did receive feedback were more likely to have actively solicited it. Overall, residents believe that this feedback from students would benefit their clinical and teaching performance. PMID- 26140122 TI - Success of a Faculty Development Program for Teachers at the Mayo Clinic. AB - BACKGROUND: There has been limited research on the improvement of underperforming clinical teachers. OBJECTIVE: To determine whether a faculty development program could improve the evaluations of clinical teachers in an internal medicine residency program. METHODS: A total of 123 teachers completed faculty development at the Mayo Clinic from 2009 to 2012. The faculty enhancement and education development program (FEED) consists of 6 interactive, small group, 2-hour sessions taught by experienced Mayo Clinic faculty over 1 year. These sessions address the following competencies: asking questions, diagnosing learners, giving feedback, using teaching frameworks, recognizing learning styles, and providing clinical supervision. Resident-of-faculty Mayo teaching effectiveness (MTE) scores have previously demonstrated content, internal structure, and criterion validity. Teachers were grouped into the top 80% or the bottom 20%, according to baseline MTE scores. Mixed linear models were used to compare these groups regarding changes in MTE scores after completion of FEED. Results were adjusted for teacher age, sex, medical specialty, academic rank, and teaching awards. RESULTS: For all participants combined, the adjusted MTE scores (mean; standard error) improved from baseline (3.80; 0.04) to completion of FEED (3.93; 0.04; P < .001). However, the bottom 20% had a significantly greater improvement in scores than the top 80% (score-change difference = 0.166, P < .001). CONCLUSIONS: We describe a low-intensity faculty development intervention that benefited all clinical teachers, but was particularly effective for underperforming teachers in internal medicine. The approach may be suitable for adoption or adaptation in other graduate medical education programs. PMID- 26140123 TI - Exploring Clinical Reasoning Strategies and Test-Taking Behaviors During Clinical Vignette Style Multiple-Choice Examinations: A Mixed Methods Study. AB - BACKGROUND: Clinical vignette multiple-choice questions (MCQs) are widely used in medical education, but clinical reasoning (CR) strategies employed when approaching these questions have not been well described. OBJECTIVES: The aims of the study were (1) to identify CR strategies and test-taking (TT) behaviors of physician trainees while solving clinical vignette MCQs; and (2) to examine the relationships between CR strategies and behaviors, and performance on a high stakes clinical vignette MCQ examination. METHODS: Thirteen postgraduate year-1 level trainees completed 6 clinical vignette MCQs using a think-aloud protocol. Thematic analysis employing elements of grounded theory was performed on data transcriptions to identify CR strategies and TT behaviors. Participants' CR strategies and TT behaviors were then compared with their US Medical Licensing Examination Step 2 Clinical Knowledge scores. RESULTS: Twelve CR strategies and TT behaviors were identified. Individuals with low performance on Step 2 Clinical Knowledge demonstrated increased premature closure and increased faulty knowledge, and showed comparatively less ruling out of alternatives or admission of knowledge deficits. High performers on Step 2 Clinical Knowledge demonstrated increased ruling out of alternatives and admission of knowledge deficits, and less premature closure, faulty knowledge, or closure prior to reading the alternatives. CONCLUSIONS: Different patterns of CR strategies and TT behaviors may be used by high and low performers during high-stakes clinical vignette MCQ examinations. PMID- 26140124 TI - Neurological Surgery Training Abroad as a Progression to the Final Year of Training and Transition to Independent Practice. AB - BACKGROUND: Residents at the University of Virginia spend 1 year abroad at a neurological surgery program prior to their chief year. The Accreditation Council for Graduate Medical Education (ACGME) considers international rotations elective experiences and does not count them toward clinical accreditation. OBJECTIVE: We compared clinical training obtained in New Zealand (NZ) to data from US ACGME accredited programs to see if it was reasonable to reconsider the former as clinical training. METHODS: We compared US national average chief case volumes to those performed by University of Virginia residents rotating in NZ over the past 3 years, using case volume comparisons and a survey of the residents' experience. RESULTS: The mean number of cases performed in NZ was above the 50th percentile for US averages for adult cranial cases, including the 70th to 90th percentile for aneurysms and 50th to 70th percentile for tumors. The average number of cases performed in 1 year in NZ satisfied the cranial case quota for 4 of 6 adult and 2 of 3 pediatric areas over the entire residency. The rotation doubled the cranial exposure of graduating residents at the chief level without diluting the experience of residents in the core program. All residents reported being "very satisfied" with the experience, noting it facilitated their transition to chief year and independent practice. CONCLUSIONS: Clinical training obtained during an international rotation in NZ is comparable to that attained in the United States. The international experience in NZ facilitated advancement in all 6 competencies, and should be considered adequate for clinical neurological surgery education. PMID- 26140125 TI - An Effective Multimodal Curriculum to Teach Internal Medicine Residents Evidence Based Breast Health. AB - BACKGROUND: Breast health is an area fraught with controversy and missed opportunities to meet women's needs, and the state of internal medicine residency training in this area is inadequate. OBJECTIVE: Our objective was to develop, implement, and evaluate a curriculum to equip internal medicine residents with the knowledge and skills to deliver high-quality, comprehensive breast health care. METHODS: We developed a 4-hour curriculum for internal medicine interns. It incorporated a team-based learning format and used MammaCare breast model software to teach and evaluate the clinical breast examination. We compared interns' precurriculum and postcurriculum test results to a historical comparison group of postgraduate year (PGY)-2 interns who did not complete the curriculum. We retested interns as PGY-2s to assess knowledge retention. RESULTS: A total 41 of 52 interns (79%) completed the curriculum. Their average MammaCare scores improved from 63% to 91%. Scores on a knowledge-based assessment improved from 47% on the pretest to 85% on the posttest (P < .001). Comparison PGY-2s who did not complete the curriculum averaged a score of 52% (P < .001). When retested 9 months after exposure to the curriculum, participants' mean score was 63% (compared to historical comparison PGY-2 group, P < .001). Only 9% of interns who retook the test as PGY-2s reported having received any breast health training subsequent to curriculum completion. CONCLUSIONS: A targeted half-day, low-cost breast health curriculum significantly improved knowledge and skills in multiple domains, and these improvements were retained in subsequent assessment despite minimal reinforcement in residency training. PMID- 26140126 TI - Refining the Practice of Prescribing: Teaching Physician Learners How to Talk to Patients About a New Prescription. AB - BACKGROUND: Clinician counseling about medication can improve patient understanding and adherence. This study developed a teaching session for physician learners about medication prescribing and communication, with evaluation at the physician and patient levels. OBJECTIVE: We analyzed whether patients would perceive and report more comprehensive clinician presentation of medication information when receiving prescriptions from their physician in the intervention clinic. METHODS: We conducted a single site, prospective intervention study that included lectures, role play, an objective standardized clinical examination (OSCE), and reminders displayed in patient care areas. For physician-level assessment, pretests and posttests included a written case presentation and a OSCE. For patient-level assessment, we used a cross-sectional observational design that included study of patient recall information, and assessment of patient satisfaction before and after intervention. RESULTS: Twenty seven family medicine residents and sports medicine fellows participated in the teaching session, focused on presenting patients the reasons, risks, and regimen of prescribed medication. In written testing, learners presented significantly more comprehensive information in posttests. In the OSCE (n = 14), all learners presented risks and regimen information. However, patient-level assessment showed no significant difference between before and after intervention. Notably, the covariates patient activation and satisfaction with communication both had a significant association with patient recall information. CONCLUSIONS: Our intervention improved learner presentation of medication information. However, patient recall of the information conveyed did not change. Although physician training did not have a positive effect on patient recall, patient activation emerged as a critical influence of patients' perceptions of medication discussions. PMID- 26140127 TI - A Clinical Process Change and Educational Intervention to Reduce the Use of Unnecessary Preoperative Tests. AB - BACKGROUND: Internal medicine residents receive limited training on how to be good stewards of health care dollars while preserving high-quality care. INTERVENTION: We implemented a clinical process change and an educational intervention focused on the appropriate use of preoperative diagnostic testing by residents at a Veterans Administration (VA) medical center. METHODS: The clinical process change consisted of reducing routine ordering of preoperative tests in the absence of specific indications. Residents received a short didactic session, which included algorithms for determining the appropriate use of perioperative diagnostic testing. One outcome was the average cost savings on preoperative testing for a continuous cohort of patients referred for elective knee or hip surgery. Resident knowledge and confidence prior to and after the intervention was measured by pre- and posttest. RESULTS: The mean cost of preoperative testing decreased from $74 to $28 per patient after the dual intervention (P < .001). The bulk of cost savings came from elimination of unnecessary blood and urine tests, as well as reduced numbers of electrocardiograms and chest radiographs. Among residents who completed the pretest and posttest, the mean score on the pretest was 54%, compared with 80% on the posttest (P = .027). Following the educational intervention, 70% of residents stated they felt "very comfortable" ordering appropriate preoperative testing (P = .006). CONCLUSIONS: This initiative required few resources, and it simultaneously improved the educational experience for residents and reduced costs. Other institutions may be able to adopt or adapt this intervention to reduce unnecessary diagnostic expenditures. PMID- 26140128 TI - Use of the QR Reader to Provide Real-Time Evaluation of Residents' Skills Following Surgical Procedures. AB - BACKGROUND: A portable electronic method of providing instructional feedback and recording an evaluation of resident competency immediately following surgical procedures has not previously been documented in obstetrics and gynecology. OBJECTIVE: This report presents a unique electronic format that documents resident competency and encourages verbal communication between faculty and residents immediately following operative procedures. METHODS: The Microsoft Tag system and SurveyMonkey platform were linked by a 2-D QR code using Microsoft QR code generator. Each resident was given a unique code (TAG) embedded onto an ID card. An evaluation form was attached to each resident's file in SurveyMonkey. Postoperatively, supervising faculty scanned the resident's TAG with a smartphone and completed the brief evaluation using the phone's screen. The evaluation was reviewed with the resident and automatically submitted to the resident's educational file. RESULTS: The evaluation system was quickly accepted by residents and faculty. Of 43 residents and faculty in the study, 38 (88%) responded to a survey 8 weeks after institution of the electronic evaluation system. Thirty (79%) of the 38 indicated it was superior to the previously used handwritten format. The electronic system demonstrated improved utilization compared with paper evaluations, with a mean of 23 electronic evaluations submitted per resident during a 6-month period versus 14 paper assessments per resident during an earlier period of 6 months. CONCLUSIONS: This streamlined portable electronic evaluation is an effective tool for direct, formative feedback for residents, and it creates a longitudinal record of resident progress. Satisfaction with, and use of, this evaluation system was high. PMID- 26140129 TI - Restoring Emphasis on Ambulatory Internal Medicine Training-The 3?1 Model. AB - BACKGROUND: Resident dissatisfaction in ambulatory care training has prompted the need for new scheduling models that support a positive learning climate. INTERVENTION: We instituted a 3?1 scheduling model for postgraduate year (PGY)-2 and PGY-3 residents. We hypothesized this model would provide a more structured ambulatory educational atmosphere, better continuity of care, and more exposure to subspecialty outpatient medicine. This model would also eliminate conflict with inpatient duties and contribute to enhance residents' satisfaction with ambulatory medicine and their ambulatory education experience. The model used weeklong ambulatory blocks every fourth week, consisting of morning continuity clinic and afternoon subspecialty clinics. The PGY-1 residents maintained a traditional schedule. RESULTS: Residents were surveyed regarding their ambulatory experience, with an overall response rate of 73 of 80 (91%). The PGY-2 and PGY-3 responses were analyzed descriptively and compared with PGY-1 responses. Residents reported that the 3?1 model positively affected their satisfaction with residency training in general, their satisfaction with outpatient/primary care training, and their outpatient/clinic educational experience. Residents in the 3?1 model perceived improvements in continuity of care and in the quality of care they provided for patients. The experience in ambulatory subspecialty training was positive. CONCLUSIONS: A 3?1 scheduling model appears to mitigate some of the conflict between inpatient and outpatient duties. Residents agreed the new model promoted an improved ambulatory experience. PMID- 26140130 TI - Text4Peds: Feasibility of an Educational Text-Messaging Program for Pediatrics Residents. AB - BACKGROUND: There is an ongoing effort to maximize educational material provided to residents who are in a time-constrained work environment. Mobile technology, principally smartphone applications and online modules, has shown educational promise. INTERVENTION: We developed a text-messaging program, Text4Peds, to assist residents with preparation for their pediatric board examinations. Goals were to assess (1) the feasibility of texting educational messages to residents, and (2) resident satisfaction and perceived usefulness of a texting program. METHODS: We conducted a prospective study of pediatrics and combined internal medicine-pediatrics residents. Messages derived from the most missed pediatric in training examination questions were sent daily to residents. After 3 months, residents completed surveys that gauged their perception on the educational value of the text messages and the effect on their pediatric board preparation. Feasibility of the system was assessed as a total percentage of messages successfully received by residents. RESULTS: Of 55 residents, 35 (64%) participated in the program. Of 2534 messages sent out to participants, 2437 (96.2%) were delivered successfully. Positive comments cited the texting of board facts as a quick, helpful, daily study tool. Residents liked that messages were sent at 2:00 pm, and most felt that 1 to 5 messages per week was appropriate. Drawbacks included character restrictions of messages, content limitations, and the lack of a question-answer format. CONCLUSIONS: An educational text message based program was successfully implemented in our residency program. Messages were delivered with a high success rate, and residents found educational value in the messages. PMID- 26140131 TI - Transforming Ward Rounds Through Rounding-in-Flow. AB - BACKGROUND: Traditional "batched" bedside clinical care rounds, where rounds for all patients precede clinical tasks, may delay clinical care and reduce resident work efficiency. INNOVATION: Using Lean concepts, we developed a novel "Rounding in-Flow" approach, with the patient care team completing all tasks for a single patient before initiating any tasks for the next patient. Outcome measures included timely patient discharge and intern work hours. METHODS: We performed a retrospective cohort study with historic and contemporaneous control groups, with time series adjustment for underlying temporal trends at a single medical center. Primary outcomes were timely patient discharge orders and resident duty hours. Participants were 17 376 consecutive hospital inpatients between January 1, 2011, and June 30, 2012, and medical ward rounding teams of interns, residents, and attending hospitalists. RESULTS: Timely discharge orders, defined as written by 9:00 am, improved from 8.6% to 26.6% (OR, 1.55; 95% CI 1.17-2.06; P = .003). Time of actual patient discharge was unchanged. Resident duty hour violations, defined as less than 10 hours between clinical duties, decreased from 2.96 to 0.98 per intern per rotation (difference, 1.98; 95% CI 1.09-2.87; P < .001). Average daily intern work hours decreased from 12.3 to 11.9 hours (difference, 0.4 hours; 95% CI 0.16-0.69; P = .002). CONCLUSIONS: Compared with batched rounding, Lean Rounding-in-Flow using "1-piece flow" principles was associated with more discharge orders written before 9:00 am and fewer violations in the 10 hour break rule, with minimal changes to intern total work hours and actual patient discharge time. PMID- 26140132 TI - The Residency Performance Index: An Effort at Residency Quality Assessment and Improvement in Family Medicine. AB - BACKGROUND: Residency programs are increasingly being asked to defend their quality, and that of the residents they produce. Yet "residency quality" is a construct that has not been well defined, with no accepted standards other than meeting accreditation standards. In 2009, the Association of Family Medicine Residency Directors developed a strategic plan that included the goal of raising the quality of family medicine training. OBJECTIVE: We describe the development of this quality improvement tool, which we called the residency performance index (RPI), and its first year of use by family medicine residency programs. We describe the use of the tool as a "dashboard" to facilitate program self improvement. INTERVENTION: Using program metrics specific to family medicine training, and benchmark criteria for these metrics, the RPI was launched in 2012 to help programs identify strengths and areas for improvement in their educational activities and resident clinical experiences that could be tracked and reviewed as part of the annual program evaluation. RESULTS: Approximately 100 program directors began using the tool and 70 finished the process, and were provided aggregate data. Initial review of this experience revealed difficulties with collecting data, and lack of information on graduates' scope of practice. It also showed the potential usefulness of the tool as a program improvement mechanism. CONCLUSIONS: The RPI is a new quality improvement tool for family medicine residency programs. Although some initial challenges need to be addressed, it has the promise to aid family medicine residency in its internal improvement efforts. PMID- 26140133 TI - Transitioning Toward Competency: A Resident-Faculty Collaborative Approach to Developing a Transitions of Care EPA in an Internal Medicine Residency Program. AB - BACKGROUND: Residency training and evaluation are moving toward competency-based models. Managing transitions of care is 1 of 16 entrustable professional activities (EPAs) that signal readiness for independent internal medicine practice. Methods for developing EPAs are evolving within the medical education community. OBJECTIVE: We describe a process for developing a transitions-of-care EPA for internal medicine inpatient and ambulatory settings using an iterative, consensus-building, resident-faculty collaborative approach. METHODS: We used an independent rank-ordering process and successive consensus group meetings to cull an initial list of 142 developmental Milestones to the 15 most relevant to transitions of care for internal medicine patients in an academic medical center and affiliated Veterans Administration hospital. Four senior internal medicine residents and 4 internal medicine faculty members representing inpatient and ambulatory practice settings identified examples of specific tasks and evaluative techniques for each Milestone. RESULTS: We demonstrate a feasible resident faculty collaboration to develop transitions of care as an EPA for an internal medicine training program. Inclusion of residents along with faculty provided broader insights as well as an important learning opportunity for trainees. CONCLUSIONS: Our process demonstrated the feasibility of designing an EPA, but questions remain about how entrustment-based evaluation can be implemented in clinical settings. Our framework may serve as a foundation for EPA development in other areas of clinical practice. PMID- 26140134 TI - Screening, Brief Intervention, Referral to Treatment (SBIRT), and Motivational Interviewing for PGY-1 Medical Residents. AB - BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) for alcohol use in primary care-often using motivational interviewing (MI)-is an effective preventive service. Medical residency programs have begun offering training in these areas, but little research has been conducted to examine the impact of SBIRT/MI training length on residents' satisfaction, affect, and behavioral intentions. OBJECTIVE: We measured residents' satisfaction with their training in addition to variables shown in previous research to predict medical professionals' intention to perform SBIRT. METHODS: This study focused on 2 SBIRT/MI training structures: a 4- to 6-hour training using didactic, experiential, and interactive methods and a brief 1-hour session explaining the same principles in a noninteractive format. Immediately following each training intervention, participating residents from internal medicine (IM), pediatrics (PEDS), medicine-pediatrics (IM-PEDS), and emergency medicine (EM) programs completed a 22-item instrument derived from established questionnaires; responses to each item were dichotomized, and comparisons were conducted between the training groups using Fisher exact test. RESULTS: Of 80 participating residents, 59 IM, PEDS, and IM-PEDS residents completed the longer training, and 21 EM residents completed the shorter training. All participating residents reported high levels of satisfaction, although EM residents were comparatively less satisfied with their shorter training session. CONCLUSIONS: Both SBIRT/MI training structures were feasible and were accepted by learners, although the 2 groups' perceptions of the training differed. Future research into the underlying causes of these differences may be useful to the application of SBIRT/MI training during residency. PMID- 26140135 TI - Educating Emergency Medicine Residents in Emergency Department Administration and Operations: Needs and Current Practice. AB - BACKGROUND: Emergency medicine (EM) residents are expected to develop competence in emergency department (ED) administration and operations. OBJECTIVES: We assessed current needs and educational practices related to preparing EM residents for their role in ED operations, and explored whether there was an association between program characteristics and the presence of ED operations education in US EM residency programs. METHODS: We conducted a cross-sectional needs assessment, using a web-based survey sent to all US EM residency programs to assess program characteristics, provision of ED operations-related lectures, availability of an ED administrative fellowship, and presence of a formal ED operations curriculum. Logistic regression was used to determine if any program characteristics were associated with the presence of lectures and a formal operations curriculum. RESULTS: Of the 158 Accreditation Council for Graduate Medical Education-accredited EM programs, 117 (74%) responded. Of these, 109 (93%) respondents had at least 1 lecture on ED operational topics. Sixty programs (54%) measured resident productivity. Knowledge of Centers for Medicaid & Medicare Services reimbursement guidelines was significantly positively associated with presence of an ED operations curriculum (OR, 3.52, P = .009) and with lectures on patient satisfaction (OR, 3.99, P = .006). Measuring resident productivity was positively associated with having lectures on productivity (OR, 2.50, P = .02) and with ED throughput (OR, 2.32, P = .03). No 2 variables were simultaneously significant in the model. CONCLUSIONS: Most EM programs had at least 1 lecture on ED operations topics. Roughly half of the programs measured resident productivity and half had a formal ED operations curriculum. PMID- 26140136 TI - Mini-Sessions on Assessment for Continuous Faculty Development. PMID- 26140137 TI - Boston Health Care for the Homeless Program-Harvard Dermatology Collaboration: A Service-Learning Model Providing Care for an Underserved Population. PMID- 26140138 TI - Clinical Evidence Summary Apps: Definition, Role, and Unknowns About a Novel Medical Content Delivery Genre. PMID- 26140139 TI - Will Automation Improve Transitions of Care? PMID- 26140140 TI - Increasing Interest in Primary Care. PMID- 26140141 TI - Transition to Practice: From Resident to Faculty at the Same Institution. PMID- 26140142 TI - Tailoring Morning Reports to an Internal Medicine Residency in Qatar. AB - BACKGROUND: Morning report, a case-based conference that allows learners and teachers to interact and discuss patient care, is a standard educational feature of internal residency programs, as well as some other specialties. OBJECTIVE: Our intervention was aimed at enhancing the format for morning report in our internal medicine residency program in Doha, Qatar. INTERVENTION: In July 2011, we performed a needs assessment of the 115 residents in our internal medicine residency program, using a questionnaire. Resident input was analyzed and prioritized using the percentage of residents who agreed with a given recommendation for improving morning report. We translated the input into interventions that enhanced the format and content, and improved environmental factors surrounding morning report. We resurveyed residents using the questionnaire that was used for the needs assessment. RESULTS: Key changes to the format for morning report included improving organization, adding variety to the content, enhancing case selection and the quality of presentations, and introducing patient safety and quality improvement topics into discussions. This led to a morning report format that is resident-driven, and resident-led, and that produces resident-focused learning and quality improvement activities. CONCLUSIONS: Our revised morning report format is a dynamic tool, and we will continue to tailor and modify it on an ongoing basis in response to participant feedback. We recommend a process of assessing and reassessing morning report for other programs that want to enhance resident interest and participation in clinical and safety-focused discussions. PMID- 26140143 TI - States Can Transform Their Health Care Workforce. AB - The United States faces the simultaneous challenges of improving health care access and balancing the specialty and geographic distribution of physicians. A 2014 Institute of Medicine report recommended significant changes in Medicare graduate medical education (GME) funding, to incentivize innovation and increase accountability for meeting national physician workforce needs. Annually, nearly $4 billion of Medicaid funds support GME, with limited accountability for outcomes. Directing these funds toward states' greatest health care workforce needs could address health care access and physician maldistribution issues and make the funding for resident education more accountable. Under the proposed approach, states would use Medicaid funds, in conjunction with Medicare GME funds, to expand existing GME programs and establish new primary care and specialty programs that focus on their population's unmet health care needs. PMID- 26140144 TI - ACGME Initiatives in Concert With Institute of Medicine Recommendations. PMID- 26140145 TI - Innovative Practices Congruent With the First Goal of the IOM 2014 Report on Graduate Medical Education. PMID- 26140146 TI - Aortic Stenosis: Changing Disease Concepts. AB - Aortic stenosis (AS) occurs in almost 10% of adults over age 80 years with a mortality about 50% at 2 years unless outflow obstruction is relieved by aortic valve replacement (AVR). Development of AS is associated with anatomic, clinical and genetic risk factors including a bicuspid valve in 50%; clinical factors that include older age, hypertension, smoking, diabetes and elevated serum lipoprotein(a) [Lp(a)] levels; and genetic factors such as a polymorphism in the Lp(a) locus. Early stages of AS are characterized by focal areas of leaflet thickening and calcification. The rate of hemodynamic progression is variable but eventual severe AS is inevitable once even mild valve obstruction is present. There is no specific medical therapy to prevent leaflet calcification. Basic principles of medical therapy for asymptomatic AS are patient education, periodic echocardiographic and clinical monitoring, standard cardiac risk factor evaluation and modification and treatment of hypertension or other comorbid conditions. When severe AS is present, a careful evaluation for symptoms is needed, often with an exercise test to document symptom status and cardiac reserve. In symptomatic patients with severe AS, AVR improves survival and relieves symptoms. In asymptomatic patients with severe AS, AVR also is appropriate if ejection fraction is < 50%, disease progression is rapid or AS is very severe (aortic velocity > 5 m/s). The choice of surgical or transcatheter AVR depends on the estimated surgical risk plus other factors such as frailty, other organ system disease and procedural specific impediments. PMID- 26140147 TI - Down Syndrome in Moderate Altitude Residents: Are There Unique Features? PMID- 26140148 TI - Prevalence of Congenital Heart Disease and Pulmonary Hypertension in Down's Syndrome: An Echocardiographic Study. AB - BACKGROUND: Down's syndrome (DS) is a genetic anomaly, which undergoes increased morbidity and mortality when associated with congenital heart disease (CHD). The aims of the study were to determine the prevalence of CHD and pulmonary hypertension (PH) in DS. METHODS: One hundred twenty-seven patients with DS living in Mexico City were evaluated by physical exam, electrocardiogram and echocardiogram. RESULTS: CHD was found in 40%. In 80% (n = 102) PH was present [systolic pulmonary artery pressure (SPAP) of 47 +/- 19 mm Hg and mean pulmonary artery pressure (MPAP) of 32 +/- 11 mm Hg]. Patients with CHD and PH were classified as having 1) no shunt (n = 18) with SPAP of 37 +/- 9 mm Hg and MPAP of 25 +/- 6 mm Hg and 2) with shunt (n = 26) with PASP of 57 +/- 29 mm Hg and MPAP of 38 +/- 19 mm Hg (p <= 0.001). In those without CHD or with CHD without shunt (n = 76), SPAP was 37 +/- 19 mm Hg and the MPAP 25 +/- 6 mm Hg. The prevalence of PH in DS was 5.9% at one year and 15% at 10 years. The odds ratio of PH in DS with CHD was 7.3 vs. 3 without CHD. CONCLUSION: DS has a high prevalence of CHD and PH. PH prevalence increases when it is associated with CHD. The pathophysiology of PH in DS without CHD should be studied in the near future. Echocardiography is an indispensible tool for evaluation of DS. PMID- 26140149 TI - Left Ventricular Strain as Predictor of Chronic Aortic Regurgitation. AB - BACKGROUND: It is not well known about the implication of left ventricular (LV) strain as a predictor for mortality in patients with chronic aortic regurgitation (AR). The purpose of this study was to investigate whether global longitudinal strain measured by two-dimensional speckle-tracking echocardiography could predict long-term outcome in patients with chronic AR. METHODS: This is a single center non-randomized retrospective observational study. The patients with chronic AR from January 2002 to December 2012 were retrospectively enrolled. Following patients were excluded; combined other significant valvular disease, previous heart surgery, aortic disease, congenital heart disease, acute AR and young age under 18 years old. Finally, 60 patients were analyzed and the LV global strain rate was measured on apical four chamber image (GS-4CH). RESULTS: During 64 months follow-up duration, 16 patients (26.7%) were deceased and 38 patients (63.3%) underwent aortic valve replacement (AVR). Deceased group was older (69 years old vs. 51 years old, p < 0.001) and had lower longitudinal strain (-12.05 +/- 3.72% vs. -15.66 +/- 4.35%, p = 0.005). Kaplan-Meier survival curve stratified by GS-4CH showed a trend of different event rate (log rank p = 0.001). On multivariate analysis by cox proportional hazard model adjusting for age, sex, body surface area, history of atrial fibrillation, blood urea nitrogen, LV dilatation, LV ejection fraction and AVR, decreased GS-4CH proved to be an independent predictor of mortality in patients with chronic AR (hazard ratio 1.313, 95% confidence interval 1.010-1.706, p = 0.042). CONCLUSION: GS-4CH may be a useful predictor of mortality in patient with chronic AR. PMID- 26140150 TI - Excessive Weight and Obesity Are Associated to Intra-Ventricular Asynchrony: Pilot Study. AB - BACKGROUND: Excessive weight and obesity (EwO) are independent factors in the development of heart failure; they lead to a state of myocardiopathy via inflammatory and hormonal mechanisms. If excessively accumulated, epicardial fat favors a proinflammatory state. Ventricular asynchrony is a marker of heart failure progression and has been poorly studied in EwO. The objective was evaluate the relation between epicardial fat, body mass index (BMI) and mechanical synchrony measured by echocardiography, in healthy individuals with EwO. METHODS: We included 55 healthy individuals between the ages of 18 and 35, 17 had a BMI < 25 kg/m(2) (30.9%) and 38 had a BMI > 25 kg/m(2) (EwO group) (69.09%), anthropometric measurements, transthoracic echocardiogram and synchrony evaluation were obtained. RESULTS: Left atrial volume, telediastolic and telesystolic left ventricular volumes and the baseline volume of the right ventricle were greater in the EwO group (20 mL/m(2) vs. 15 mL/m(2), p = 0.001; 106 mL vs. 82 mL, p = 0.0149 vs. 32 mL, p = 0.001 and 34 mm vs. 31 mm, p = 0.02, respectively). The Yu index also correlated with epicardial fat, r = 0.53, p < 0.01, whereby the greater the amount of epicardial fat, the greater the dispersion timing of ventricular activation. The systolic synchrony index also correlated with the BMI, p = 0.01. CONCLUSION: Mechanical intraventricular asynchrony is associated to EwO and the amount of epicardial fat; hence, asynchrony may be one more factor leading to heart failure in EwO individuals. PMID- 26140151 TI - Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension. AB - BACKGROUND: New 2-dimensional strain echocardiography enables quantification of right ventricular (RV) mechanics by assessing global longitudinal strain of RV (GLSRV) in patients with pulmonary arterial hypertension (PAH). However, the prognostic significance of impaired GLSRV is unclear in these patients. METHODS: Comprehensive echocardiography was performed in 51 consecutive PAH patients without atrial fibrillation (40 females, 48 +/- 14 years old) with long-term follow-up. GLSRV was measured with off-line with velocity vector imaging (VVI, Siemens Medical System, Mountain View, CA, USA). RESULTS: GLSRV showed significant correlation with RV fractional area change (r = -0.606, p < 0.001), tricuspid annular plane systolic excursion (r = -0.579, p < 0.001), and RV Tei index (r = 0.590, p < 0.001). It showed significant correlations with pulmonary vascular resistance (r = 0.469, p = 0.001) and B-natriuretic peptide concentration (r = 0.351, p = 0.012). During a clinical followup time (45 +/- 15 months), 20 patients experienced one or more adverse events (12 death, 2 lung transplantation, and 15 heart failure hospitalization). After multivariate analysis, age [hazard ratio (HR) = 2.343, p = 0.040] and GLSRV (HR = 2.122, p = 0.040) were associated with adverse clinical events. Age (HR = 3.200, p = 0.016) and GLSRV (HR = 2.090, p = 0.042) were also significant predictors of death. Impaired GLSRV (>= -15.5%) was associated with lower event-free survival (HR = 4.906, p = 0.001) and increased mortality (HR = 8.842, p = 0.005). CONCLUSION: GLSRV by VVI showed significant correlations with conventional echocardiographic parameters indicating RV systolic function. Lower GLSRV (>= -15.5%) was significantly associated with presence of adverse clinical events and deaths in PAH patients. PMID- 26140152 TI - A Hypereosinophilic Syndrome with Cardiac Involvement from Thrombotic Stage to Fibrotic Stage. AB - Cardiac involvement is a major cause of morbidity and mortality in hypereosinophilic syndrome (HES). It is classified into 3 stages by the degree of eosinophils-mediated heart injury; acute necrotic stage, thrombotic stage, and fibrotic stage. Nonetheless, definitive evidence that each patient passes sequentially through these stages is lacking. We present a case of 48-year-old male patient with dyspnea and peripheral edema who underwent valve replacement surgery due to severe mitral regurgitation. After the valve replacement, HES with cardiac involvement in the thrombotic stage was diagnosed. In the follow-up study, the patient progressed into fibrotic stage of HES. PMID- 26140153 TI - Surgical Removal of a Left Ventricular Thrombus Which Showed Morphologic Changes Over Time in a Patient with Stress-Induced Cardiomyopathy. AB - Although stress-induced cardiomyopathy (SCMP) is a reversible disease and the prognosis is usually excellent, several complications can occur and can result in fatal adverse events. The formation of left ventricular (LV) thrombus is one of these critical complications of SCMP. This report describes a case of SCMP complicated by formation of a LV thrombus that became increasingly mobile as LV contractility recovered, and for which surgical removal was performed. Here, we report a case of SCMP complicated by LV thrombus and review the literature regarding this topic. PMID- 26140154 TI - Unusual Diaphragmatic Hernias Mimicking Cardiac Masses. AB - Hiatal hernia and Morgagni hernia are sorts of diaphragmatic hernias that are rarely detected on transthoracic echocardiography. Although echocardiographic findings have an important role for differential diagnosis of cardiac masses, we often might overlook diaphragmatic hernia. We report three cases of diaphragmatic hernias having specific features. The first case is huge hiatal hernia that encroaches left atrium with internal swirling flow on transthoracic echocardiography. The second case is a hiatal hernia that encroaches on both atria, incidentally detected on preoperative echocardiography. The third case is Morgagni hernia which encroaches on the right atrium only. So, we need to consider possibility of diaphragmatic hernia when we find a cardiac mass with specific echocardiographic features. PMID- 26140155 TI - A Case of Perimembranous Ventricular Septal Defect Associated with Sinus of Valsalva Aneurysm Mimicking Membranous Septal Aneurysm. AB - Sinus of Valsalva aneurysms are rare. Sinus of Valsalva aneurysms are frequently associated with ventricular septal defect (VSD) and aortic regurgitation. They often remain asymptomatic until abruptly presenting with acute chest pain and heart failure secondary to rupture. Here, we describe a case of 20-year-old man who presented with chest pain with a history of VSD. Initial work-up concluded that the patient had VSD associated membranous septal aneurysm. Four years later, the patient presented with symptoms of heart failure. Work-up showed that the ruptured sinus of Valsalva aneurysm was the cause of symptoms. Due to its close proximity to the aortic annulus, sinus of Valsalva aneurysm should be differentiated from membranous septal aneurysm. PMID- 26140156 TI - Giant Carotid Pseudoaneurysm. PMID- 26140157 TI - Simultaneous Bilateral Infective Endocarditis with Right Ventricular Mural Involvement. PMID- 26140158 TI - Karyotype analysis and visualization of 45S rRNA genes using fluorescence in situ hybridization in aroids (Araceae). AB - Karyotype analysis and FISH mapping using 45S rDNA sequences on 6 economically important plant species Anthuriumandraeanum Linden ex Andre, 1877, Monsteradeliciosa Liebmann, 1849, Philodendronscandens Koch & Sello, 1853, Spathiphyllumwallisii Regel, 1877, Syngoniumauritum (Linnaeus, 1759) Schott, 1829 and Zantedeschiaelliottiana (Knight, 1890) Engler, 1915 within the monocotyledonous family Araceae (aroids) were performed. Chromosome numbers varied between 2n=2x=24 and 2n=2x=60 and the chromosome length varied between 15.77 um and 1.87 um. No correlation between chromosome numbers and genome sizes was observed for the studied genera. The chromosome formulas contained only metacentric and submetacentric chromosomes, except for Philodendronscandens in which also telocentric and subtelocentric chromosomes were observed. The highest degree of compaction was calculated for Spathiphyllumwallisii (66.49Mbp/um). B chromosome-like structures were observed in Anthuriumandraeanum. Their measured size was 1.87 times smaller than the length of the shortest chromosome. After FISH experiments, two 45S rDNA sites were observed in 5 genera. Only in Zantedeschiaelliottiana, 4 sites were seen. Our results showed clear cytogenetic differences among genera within Araceae, and are the first molecular cytogenetics report for these genera. These chromosome data and molecular cytogenetic information are useful in aroid breeding programmes, systematics and evolutionary studies. PMID- 26140159 TI - Ribosomal DNA clusters and telomeric (TTAGG)n repeats in blue butterflies (Lepidoptera, Lycaenidae) with low and high chromosome numbers. AB - Ribosomal DNA clusters and telomeric repeats are important parts of eukaryotic genome. However, little is known about their organization and localization in karyotypes of organisms with holocentric chromosomes. Here we present first cytogenetic study of these molecular structures in seven blue butterflies of the genus Polyommatus Latreille, 1804 with low and high chromosome numbers (from n=10 to n=ca.108) using fluorescence in situ hybridization (FISH) with 18S rDNA and (TTAGG) n telomeric probes. FISH with the 18S rDNA probe showed the presence of two different variants of the location of major rDNA clusters in Polyommatus species: with one or two rDNA-carrying chromosomes in haploid karyotype. We discuss evolutionary trends and possible mechanisms of changes in the number of ribosomal clusters. We also demonstrate that Polyommatus species have the classical insect (TTAGG) n telomere organization. This chromosome end protection mechanism probably originated de novo in small chromosomes that evolved via fragmentations. PMID- 26140160 TI - Karyotypical characteristics of two allopatric African populations of anhydrobiotic Polypedilum Kieffer, 1912 (Diptera, Chironomidae) originating from Nigeria and Malawi. AB - The African chironomid Polypedilumvanderplanki Hinton, 1951 is the only chironomid able to withstand almost complete desiccation in an ametabolic state known as anhydrobiosis. The karyotypes of two allopatric populations of this anhydrobiotic chironomid, one from Nigeria and another from Malawi, were described according to the polytene giant chromosomes. The karyotype from the Nigerian population was presented as the reference chromosome map for Polypedilumvanderplanki. Both populations, Nigerian and Malawian, showed the same number of chromosomes (2n=8), but important differences were found in the band sequences of polytene chromosomes, and in the number and the arrangement of active regions between the two populations. Such important differences raise the possibility that the Malawian population could constitute a distinct new species of anhydrobiotic chironomid. PMID- 26140161 TI - Genomic in situ hybridization identifies parental chromosomes in hybrid scallop (Bivalvia, Pectinoida, Pectinidae) between female Chlamysfarreri and male Argopectenirradiansirradians. AB - Interspecific crossing was artificially carried out between Chlamysfarreri (Jones & Preston, 1904) ? and Argopectenirradiansirradians (Lamarck, 1819) ?, two of the dominant cultivated scallop species in China. Genomic in situ hybridization (GISH) was used to examine the chromosome constitution and variation in hybrids at early embryonic stage. The number of chromosomes in 66.38% of the metaphases was 2n = 35 and the karyotype was 2n = 3 m + 5 sm + 16 st + 11 t. After GISH, two parental genomes were clearly distinguished in hybrids, most of which comprised 19 chromosomes derived from their female parent (Chlamysfarreri) and 16 chromosomes from their male parent (Argopectenirradiansirradians). Some chromosome elimination and fragmentation was also observed in the hybrids. PMID- 26140162 TI - Chromosomal organization of the ribosomal RNA genes in the genus Chironomus (Diptera, Chironomidae). AB - Chromosomal localization of ribosomal RNA coding genes has been studied by using FISH (fluorescence in situ hybridization) in 21 species from the genus Chironomus Meigen, 1803. Analysis of the data has shown intra- and interspecific variation in number and location of 5.8S rDNA hybridization sites in 17 species from the subgenus Chironomus and 4 species from the subgenus Camptochironomus Kieffer, 1914. In the majority of studied species the location of rDNA sites coincided with the sites where active NORs (nucleolus organizer regions) were found. The number of hybridization sites in karyotypes of studied chironomids varied from 1 to 6. More than half of the species possessed only one NOR (12 out of 21). Two rDNA hybridization sites were found in karyotypes of five species, three - in two species, and five and six sites - in one species each. NORs were found in all chromosomal arms of species from the subgenus Chironomus with one of them always located on arm G. On the other hand, no hybridization sites were found on arm G in four studied species from the subgenus Camptochironomus. Two species from the subgenus Chironomus - Chironomusbalatonicus Devai, Wuelker & Scholl, 1983 and Chironomus "annularius" sensu Strenzke, 1959 - showed intraspecific variability in the number of hybridization signals. Possible mechanisms of origin of variability in number and location of rRNA genes in the karyotypes of species from the genus Chironomus are discussed. PMID- 26140163 TI - Chromosomes of Belonocnematreatae Mayr, 1881 (Hymenoptera, Cynipidae). AB - Chromosomes of the asexual and sexual generation of the gall wasp Belonocnematreatae Mayr, 1881 (Cynipidae) were analyzed. Females of both generations have 2n = 20, whereas males of the sexual generation have n = 10. Cyclical deuterotoky is therefore confirmed in this species. All chromosomes are acrocentric and form a continuous gradation in size. This karyotype structure is probably ancestral for many gall wasps and perhaps for the family Cynipidae in general. Chromosome no. 7 carries a characteristic achromatic gap that appears to represent a nucleolus organizing region. PMID- 26140164 TI - Cytogenetic analysis of Scinaxauratus and Scinaxeurydice (Anura, Hylidae) with emphasis on cytotaxonomy. AB - Scinax Wagler, 1830 is a species-rich genus of amphibians with relatively few detailed chromosomal reports. In this work, cytogenetic analyses of Scinaxauratus (Wied-Neuwied, 1821) and Scinaxeurydice (Bokermann, 1968) were carried out based on conventional (Giemsa staining, Ag-NOR and C-banding) and cytomolecular (base specific fluorochrome staining and fluorescence in situ hybridization - FISH of ribosomal probes) techniques. Both species shared the same karyotype, location of active nucleolar organizer regions on pair 11 and GC-rich heterochromatin, as reported for most species in Scinaxruber clade. Interpopulation chromosomal variation was observed in Scinaxeurydice, indicating the occurrence of cryptic species. The mapping of 18S ribosomal genes by FISH is reported for the first time in both species. PMID- 26140165 TI - Comparative analysis of karyotypes of Chironomussolitus Linevich & Erbaeva, 1971 and Chironomusanthracinus Zetterstedt, 1860 (Diptera, Chironomidae) from East Siberia. AB - A comparative chromosome banding analysis of Chironomussolitus Linevich & Erbaeva, 1971 and Chironomusanthracinus Zetterstedt, 1860 from East Siberia (Lakes Baikal, Gusinoe, Arakhley and Irkutsk Reservoir) showed close similarity of banding sequences. Chironomussolitus differs from Chironomusanthracinus in one species-specific sequence of arm B. Arms C (43%) and D (30%) had inversion banding sequences previously reported in Chironomusanthracinus The similarity of karyotypic features of Chironomussolitus and Chironomusanthracinus in combination with morphological features of larvae provide evidence in favour of including Chironomussolitus in the Chironomusanthracinus group of sibling species long with Chironomusreservatus Shobanov, 1997. PMID- 26140166 TI - Chromosomal and molecular evidence for presence of Polyommatus (Agrodiaetus) poseidon (Lepidoptera, Lycaenidae) in Caucasus region. AB - We show how combination of chromosomal and molecular markers can be applied for proper species identification in Agrodiaetus Hubner, 1822 blue butterflies. Using this approach we provide first evidence for presence of Polyommatus (Agrodiaetus) poseidon (Herrich-Schaffer, [1851]) in Georgia. PMID- 26140167 TI - Phylogenetic relationships of some species of the family Echinostomatidae Odner, 1910 (Trematoda), inferred from nuclear rDNA sequences and karyological analysis. AB - The family Echinostomatidae Looss, 1899 exhibits a substantial taxonomic diversity, morphological criteria adopted by different authors have resulted in its subdivision into an impressive number of subfamilies. The status of the subfamily Echinochasminae Odhner, 1910 was changed in various classifications. Genetic characteristics and phylogenetic analysis of four Echinostomatidae species - Echinochasmus sp., Echinochasmuscoaxatus Dietz, 1909, Stephanoprorapseudoechinata (Olsson, 1876) and Echinoparyphiummordwilkoi Skrjabin, 1915 were obtained to understand well enough the homogeneity of the Echinochasminae and phylogenetic relationships within the Echinostomatidae. Chromosome set and nuclear rDNA (ITS2 and 28S) sequences of parthenites of Echinochasmus sp. were studied. The karyotype of this species (2n=20, one pair of large bi-armed chromosomes and others are smaller-sized, mainly one-armed, chromosomes) differed from that previously described for two other representatives of the Echinochasminae, Echinochasmusbeleocephalus (von Linstow, 1893), 2n=14, and Episthmiumbursicola (Creplin, 1937), 2n=18. In phylogenetic trees based on ITS2 and 28S datasets, a well-supported subclade with Echinochasmus sp. and Stephanoprorapseudoechinata clustered with one well supported clade together with Echinochasmusjaponicus Tanabe, 1926 (data only for 28S) and Echinochasmuscoaxatus. These results supported close phylogenetic relationships between Echinochasmus Dietz, 1909 and Stephanoprora Odhner, 1902. Phylogenetic analysis revealed a clear separation of related species of Echinostomatoidea restricted to prosobranch snails as first intermediate hosts, from other species of Echinostomatidae and Psilostomidae, developing in Lymnaeoidea snails as first intermediate hosts. According to the data based on rDNA phylogeny, it was supposed that evolution of parasitic flukes linked with first intermediate hosts. Digeneans parasitizing prosobranch snails showed higher dynamic of karyotype evolution provided by different chromosomal rearrangements including Robertsonian translocations and pericentric inversions than more stable karyotype of digenean worms parasitizing lymnaeoid pulmonate snails. PMID- 26140168 TI - First description of the karyotype and localization of major and minor ribosomal genes in Rhoadsiaaltipinna Fowler, 1911 (Characiformes, Characidae) from Ecuador. AB - Karyotypic features of Rhoadsiaaltipinna Fowler, 1911 from Ecuador were investigated by examining metaphase chromosomes through Giemsa staining, C banding, Ag-NOR, and two-color-fluorescence in situ hybridization (FISH) for mapping of 18S and 5S ribosomal genes. The species exhibit a karyotype with 2n = 50, composed of 10 metacentric, 26 submetacentric and 14 subtelocentric elements, with a fundamental number FN=86 and is characterized by the presence of a larger metacentric pair (number 1), which is about 2/3 longer than the average length of the rest of the metacentric series. Sex chromosomes were not observed. Heterochromatin is identifiable on 44 chromosomes, distributed in paracentromeric position near the centromere. The first metacentric pair presents two well defined heterochromatic blocks in paracentromeric position, near the centromere. Impregnation with silver nitrate showed a single pair of Ag-positive NORs localized at terminal regions of the short arms of the subtelocentric chromosome pair number 12. FISH assay confirmed these localization of NORs and revealed that minor rDNA clusters occur interstitially on the larger metacentric pair number 1. Comparison of results here reported with those available on other Characidae permit to hypothesize that the presence of a very large metacentric pair might represent a unique and derived condition that characterize one of four major lineages molecularly identified in this family. PMID- 26140169 TI - Influence of preparation depths on the fracture load of customized zirconia abutments with titanium insert. AB - PURPOSE: This study evaluated the fracture load of customized zirconia abutments with titanium insert according to preparation depths, with or without 5-year artificial aging. MATERIALS AND METHODS: Thirty-six identical lithium disilicate crowns (IPS e.max press) were fabricated to replace a maxillary right central incisor and cemented to the customized zirconia abutment with titanium insert on a 4.5*10 mm titanium fixture. Abutments were fabricated with 3 preparation depths (0.5 mm, 0.7 mm, and 0.9 mm). Half of the samples were then processed using thermocycling (temperature: 5-55C, dwelling time: 120s) and chewing simulation (1,200,000 cycles, 49 N load). All specimens were classified into 6 groups depending on the preparation depth and artificial aging (non-artificial aging groups: N5, N7, N9; artificial aging groups: A5, A7, A9). Static load was applied at 135 degrees to the implant axis in a universal testing machine. Statistical analyses of the results were performed using 1-way ANOVA, 2-way ANOVA, independent t-test and multiple linear regression. RESULTS: The fracture loads were 539.28 +/- 63.11 N (N5), 406.56 +/- 28.94 N (N7), 366.66 +/- 30.19 N (N9), 392.61 +/- 50.57 N (A5), 317.94 +/- 30.05 N (A7), and 292.74 +/- 37.15 N (A9). The fracture load of group N5 was significantly higher than those of group N7 and N9 (P<.017). Consequently, the fracture load of group A5 was also significantly higher than those of group A7 and A9 (P<.05). After artificial aging, the fracture load was significantly decreased in all groups with various preparation depths (P<.05). CONCLUSION: The fracture load of a single anterior implant restored with lithium disilicate crown on zirconia abutment with titanium insert differed depending on the preparation depths. After 5-year artificial aging, the fracture loads of all preparation groups decreased significantly. PMID- 26140170 TI - Comparison of marginal bone loss and patient satisfaction in single and double implant assisted mandibular overdenture by immediate loading. AB - PURPOSE: The purpose of this study was to compare the coronal bone level and patient satisfaction in 1-implant and 2-implant assisted mandibular overdentures. MATERIALS AND METHODS: Twenty patients who had maladaptive mandibular dentures were treated in this study. Patients were randomly divided into two groups. The first group received 1 implant (Simple line II, Implantium, South Korea) in their mandibular midline and the second group received 2 implants in their B and D regions (according to Misch's category). If the primary stability of each implant was at least 60 ISQ, ball attachment was placed and denture relined with soft liner. After 6 weeks, retentive cap incorporated with hard acrylic resin. In the 6 and 12 months recalls, periapical digital radiograph were made and visual analogue scale questionnaires were used to record patient satisfaction. The Friedman test was done for comparing the presurgical and postsurgical parameters in each group and the U-Mann Whitney test (P<.05) was done for comparison of post treatment results between the two groups. RESULTS: All implants achieved sufficient primary stability to be immediately loaded. Patient satisfaction was high, and there were no significant differences between two groups (P>.05). In addition, mean marginal bone loss was 0.6 +/- 0.67 mm in the first group and 0.6 +/- 0.51 mm in the second group, after 12 month. Mean marginal bone loss showed no significant differences between two groups. CONCLUSION: This preliminary one year result indicated that mandibular overdentures anchored to a single implant can be a safe and cost-effective method as a starting step for implant overdenture treatment. PMID- 26140171 TI - Impact of surface roughness of gypsum materials on adaptation of zirconia cores. AB - PURPOSE: The present study investigated the influences of various gypsum materials on the precision of fit of CAD/CAM-fabricated prostheses and analyzed their correlation with surface roughness. MATERIALS AND METHODS: The master model of the mandibular right first molar was replicated, and four experimental groups based on two types of Type IV stone (GC Fujirock EP, Die keen) and two types of scannable stone (Aesthetic-Basegold, Everest Rock) were created to include a total of 40 specimens, 10 in each group. The surface roughness of the working models for the respective experimental groups was measured. Once the zirconia cores had been fabricated, the marginal and internal fits were measured with a digital microscope using the silicone replica technique. The mean and standard deviation of the respective points of measurement were computed and analyzed through the one-way ANOVA and Tukey's HSD test. The correlation between surface roughness and the precision of fit of the zirconia core was analyzed using the Pearson correlation analysis (alpha=.05). RESULTS: The zirconia cores fabricated from the scannable stone working models exhibited a superior precision of fit as compared to those fabricated from the Type IV stone working models. The correlation analysis results showed a clear positive correlation between surface roughness and the precision of fit of zirconia cores in all of the experimental groups (P<.05). CONCLUSION: The results confirmed that the surface roughness of dental working models has a decisive influence on the precision of fit of zirconia cores. PMID- 26140172 TI - Effect of cement washout on loosening of abutment screws and vice versa in screw- and cement- retained implant-supported dental prosthesis. AB - PURPOSE: The purpose of this study was to examine the abutment screw stability of screw- and cement-retained implant-supported dental prosthesis (SCP) after simulated cement washout as well as the stability of SCP cements after complete loosening of abutment screws. MATERIALS AND METHODS: Thirty-six titanium CAD/CAM made implant prostheses were fabricated on two implants placed in the resin models. Each prosthesis is a two-unit SCP: one screw-retained and the other cemented. After evaluating the passive fit of each prosthesis, all implant prostheses were randomly divided into 3 groups: screwed and cemented SCP (Control), screwed and noncemented SCP (Group 1), unscrewed and cemented SCP (Group 2). Each prosthesis in Control and Group 1 was screwed and/or cemented, and the preloading reverse torque value (RTV) was evaluated. SCP in Group 2 was screwed and cemented, and then unscrewed (RTV=0) after the cement was set. After cyclic loading was applied, the postloading RTV was measured. RTV loss and decementation ratios were calculated for statistical analysis. RESULTS: There was no significant difference in RTV loss ratio between Control and Group 1 (P=.16). No decemented prosthesis was found among Control and Group 2. CONCLUSION: Within the limits of this in vitro study, the stabilities of SCP abutment screws and cement were not significantly changed after simulated cement washout or screw loosening. PMID- 26140173 TI - The effect of various sandblasting conditions on surface changes of dental zirconia and shear bond strength between zirconia core and indirect composite resin. AB - PURPOSE: To measure the surface loss of dental restorative zirconia and the short term bond strength between an indirect composite resin (ICR) and zirconia ceramic after various sandblasting processes. MATERIALS AND METHODS: Three hundred zirconia bars were randomly divided into 25 groups according to the type of sandblasting performed with pressures of 0.1, 0.2, 0.4 and 0.6 MPa, sandblasting times of 7, 14 and 21 seconds, and alumina powder sizes of 50 and 110 um. The control group did not receive sandblasting. The volume loss and height loss on zirconia surface after sandblasting and the shear bond strength (SBS) between the sandblasted zirconia and ICR after 24-h immersion were measured for each group using multivariate analysis of variance (ANOVA) and Least Significance Difference (LSD) test (alpha=.05). After sandblasting, the failure modes of the ICR/zirconia surfaces were observed using scanning electron microscopy. RESULTS: The volume loss and height loss were increased with higher sandblasting pressure and longer sandblasting treatment, but they decreased with larger powder size. SBS was significantly increased by increasing the sandblasting time from 7 seconds to 14 seconds and from 14 seconds to 21 seconds, as well as increasing the size of alumina powder from 50 um to 110 um. SBS was significantly increased from 0.1 MPa to 0.2 MPa according to the size of alumina powder. However, the SBSs were not significantly different with the sandblasting pressure of 0.2, 0.4 and 0.6 MPa. The possibilities of the combination of both adhesive failure and cohesive failure within the ICR were higher with the increases in bonding strength. CONCLUSION: Based on the findings of this study, sandblasting with alumina particles at 0.2 MPa, 21 seconds and the powder size of 110 um is recommended for dental applications to improve the bonding between zirconia core and ICR. PMID- 26140174 TI - The effect of IDS (immediate dentin sealing) on dentin bond strength under various thermocycling periods. AB - PURPOSE: The purpose of this study was to find out the effect of immediate dentin sealing (IDS) on bond strength of ceramic restoration under various thermocycling periods with DBA (dentin bonding agent system). MATERIALS AND METHODS: Fifty freshly extracted human mandibular third molars were divided into 5 groups (1 control and 4 experimental groups) of 10 teeth. We removed enamel layer of sound teeth and embedded them which will proceed to be IDS, using All Bond II. A thermocycling was applied to experimental groups for 1, 2, 7, 14 days respectively and was not applied to control group. IPS Empress II for ceramic was acid-etched with ceramic etchant (9.5% HF) and silane was applied. Each ceramic disc was bonded to specimens with Duo-link, dual curable resin cement by means of light curing for 100 seconds. After the cementation procedures, shear bond strength measurement and SEM analysis of the fractured surface were done. The data were analyzed with a one-way ANOVA and Tukey multiple comparison test (alpha=.05). RESULTS: There were no statistically significant differences between 4 experimental groups and control group, however the mean value started to decrease in group 7d, and group 14d showed the lowest mean bond strength in all groups. Also, group 7d and 14d showed distinct exposed dentin and collapsed hybrid layer was observed in SEM analysis. CONCLUSION: In the present study, it can be concluded that ceramic restorations like a laminate veneer restoration should be bonded using resin cement within one week after IDS procedure. PMID- 26140175 TI - The effect of various veneering techniques on the marginal fit of zirconia copings. AB - PURPOSE: This study aimed to evaluate the fit of zirconia ceramics before and after veneering, using 3 different veneering processes (layering, press-over, and CAD-on techniques). MATERIALS AND METHODS: Thirty standardized zirconia CAD/CAM frameworks were constructed and divided into three groups of 10 each. The first group was veneered using the traditional layering technique. Press-over and CAD on techniques were used to veneer second and third groups. The marginal gap of specimens was measured before and after veneering process at 18 sites on the master die using a digital microscope. Paired t-test was used to evaluate mean marginal gap changes. One-way ANOVA and post hoc tests were also employed for comparison among 3 groups (alpha=.05). RESULTS: Marginal gap of 3 groups was increased after porcelain veneering. The mean marginal gap values after veneering in the layering group (63.06 um) was higher than press-over (50.64 um) and CAD-on (51.50 um) veneered groups (P<.001). CONCLUSION: Three veneering methods altered the marginal fit of zirconia copings. Conventional layering technique increased the marginal gap of zirconia framework more than pressing and CAD-on techniques. All ceramic crowns made through three different veneering methods revealed clinically acceptable marginal fit. PMID- 26140176 TI - Does matching relation exist between the length and the tilting angle of terminal implants in the all-on-four protocol? stress distributions by 3D finite element analysis. AB - PURPOSE: To explore whether there is matching relation between the length and the tilting angle of terminal implants in the All-on-Four protocol by studying the effects of different implant configurations on stress distributions of implant, bone, and framework. MATERIALS AND METHODS: Four implants were employed to support a full-arch fixed prosthesis and five three-dimensional finite element models were established with CT images, based on the length (S and L) and distal tilt angle (0 degrees , 30 degrees and 45 degrees ) of terminal implants for an edentulous mandible, which named: Tilt0-S, Tilt30-S, Tilt30-L, Tilt45-S and Tilt45-L. An oblique 240 N was loaded at second molar. The von Mises Stresses were analyzed. The implants were consecutively named #1 to #4 from the loading point. RESULTS: 1) Tilt0-S had the greatest stress on the implants, with the other groups exhibiting variable reductions; the four implants of Tilt45-L demonstrated the greatest reduction in stress. 2) Tilt0-S had the greatest stress at bone around #1 implant neck, and Tilt45-L exhibited the least stress, which was a 36.3% reduction compared to Tilt0-S. 3) The greatest stress in the framework was found on the cantilevers distal to #1 implant. Tilt45-S exhibited the least stress. CONCLUSION: Matching different length and tilting angle of the terminal implants led to variable stress reductions on implants, bone and the superstructure. By optimizing implant configuration, the reduction of stress on implants and surrounding bone could be maximized. Under the present condition, Tilt45-L was the preferred configuration. Further clinical testings are required. PMID- 26140177 TI - Effect of atmospheric plasma versus conventional surface treatments on the adhesion capability between self-adhesive resin cement and titanium surface. AB - PURPOSE: The aim of this study was to evaluate the effects of atmospheric plasma (APL) versus conventional surface treatments on the adhesion of self-adhesive resin cement to Ti-6Al-4V alloy. MATERIALS AND METHODS: Sixty plates of machined titanium (Ti) discs were divided into five groups (n=12): 1) Untreated (CNT); 2) Sandblasted (SAB); 3) Tribochemically treated (ROC); 4) Tungsten CarbideBur (TCB); 5) APL treated (APL). SEM analysis and surface roughness (Ra) measurements were performed. Self-adhesive resin cement was bonded to the Ti surfaces and shear bond strength (SBS) tests, Ra and failure mode examinations were carried out. Data were analyzed by one-way analysis of variance and chi-squared test. RESULTS: The lowest SBS value was obtained with CNT and was significantly different from all other groups except for APL. The ROC showed the highest SBS and Ra values of all the groups. CONCLUSION: It was concluded that the effect of APL on SBS and Ra was not sufficient and it may not be a potential for promoting adhesion to titanium. PMID- 26140178 TI - Evaluation and comparison of the marginal adaptation of two different substructure materials. AB - PURPOSE: In this study, we aimed to evaluate the amount of marginal gap with two different substructure materials using identical margin preparations. MATERIALS AND METHODS: Twenty stainless steel models with a chamfer were prepared with a CNC device. Marginal gap measurements of the galvano copings on these stainless steel models and Co-Cr copings obtained by a laser-sintering method were made with a stereomicroscope device before and after the cementation process and surface properties were evaluated by scanning electron microscopy (SEM). A dependent t-test was used to compare the mean of the two groups for normally distributed data, and two-way variance analysis was used for more than two data sets. Pearson's correlation analysis was also performed to assess relationships between variables. RESULTS: According to the results obtained, the marginal gap in the galvano copings before cementation was measured as, on average, 24.47 +/- 5.82 um before and 35.11 +/- 6.52 um after cementation; in the laser-sintered Co Cr structure, it was, on average, 60.45 +/- 8.87 um before and 69.33 +/- 9.03 um after cementation. A highly significant difference (P<.001) was found in marginal gap measurements of galvano copings and a significant difference (P<.05) was found in marginal gap measurements of the laser-sintered Co-Cr copings. According to the SEM examination, surface properties of laser sintered Co-Cr copings showed rougher structure than galvano copings. The galvano copings showed a very smooth surface. CONCLUSION: Marginal gaps values of both groups before and after cementation were within the clinically acceptable level. The smallest marginal gaps occurred with the use of galvano copings. PMID- 26140179 TI - Implant-supported overdenture manufactured using CAD/CAM techniques to achieve horizontal path insertion between the primary and secondary structure: A clinical case report. AB - This report describes the case of an edentulous patient with an atrophic maxilla and severe class III malocclusion. Prosthetic rehabilitation was performed using CAD/CAM techniques for manufacturing an implant-supported overdenture with horizontal insertion. A vestibulo-lingual insertion overdenture is a precision prosthesis with a fixation system affording a good fit between the primary and secondary structure. Both structures exhibit passive horizontal adjustment. This treatment option requires the same number of implants as implant-supported fixed dentures. The horizontal assembly system prevents the prosthesis from loosening or moving in response to axial and non-axial forces. The technique was used to rehabilitate a patient presenting an atrophic upper maxilla, with the insertion of 8 implants. No complications were reported at follow-up 3, 6 and 12 months after fitting of the prosthesis. This system offers solutions to the clinical and laboratory complications associated with hybrid prostheses, concealing emergence of the chimneys and improving implant-prosthesis hygiene. PMID- 26140180 TI - IVF Technology. PMID- 26140181 TI - Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma. AB - BACKGROUND: High expression of telomerase and Bcl-2 are reported in hepatocellular carcinoma. Some anticancer drugs show their effects through reduction of these factors. In this study, it was aimed to investigate the effects of a new synthetic compound, platinum azidothymidine, on inhibition of telomerase and Bcl-2 expression in hepatocellular carcinoma compared to azidothymidine. METHODS: To study the effects of Pt-AZT on hepatocellular carcinoma and compare its effects with AZT in inhibition of telomerase and Bcl-2 gene expression, pathogen-free male Wistar rats (n=100) were used. They were randomly divided to 4 groups (n=25). Group A as the control group contained 25 healthy rats; in the rest of animals, preneoplastic lesions were induced in their livers (groups B, C, and D) using Solt-Farber resistant hepatocyte protocol. Cancer development was approved by a pathology laboratory. Group B was negative control (untreated), groups C and D were treated by intraperitoneal injection (IP) of Pt-AZT (0.9 mg/kg/day) and AZT (0.3 mg/kg/day), respectively for 14 days. At the end of the protocol, all rats were sacrificed and Bcl-2 and telomerase gene expression was determined using real-time PCR. RESULTS: No tumor in the livers was found in group A at any point of the study, but it was present in livers of all animals in B, C and D groups. Results showed that telomerase and Bcl-2 expression was significantly lower in group C compared with group B (0.473+/-0.231 vs. 5.137+/-5.08, p<0.001, for telomerase expression, and 0.41+/ 0.276 vs. 7.25+/-11.6, p<0.001, for Bcl-2 expression) and also compared with group D (0.473+/-0.231 vs. 3.48+/-4.02, p<0.001, for telomerase expression, and 0.41+/-0.276 vs. 4.93+/-18, p<0.001, for Bcl-2 expression). CONCLUSION: For the first time, it was demonstrated that Pt-AZT has more inhibitory effect on telomerase and Bcl-2 expression than AZT. It effectively inhibits the growth of liver tumor in rats by extending apoptosis. PMID- 26140182 TI - The Effects of Ultraviolet Light and Riboflavin on Inactivation of Viruses and the Quality of Platelet Concentrates at Laboratory Scale. AB - BACKGROUND: This study investigated the effects of Riboflavin (RB) combined with different doses of UV on Platelet Concentrate (PC) which was infected by three models of virus. Platelet quality after treatment was also assessed. METHODS: Three models of virus used in this study were Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus (HSV), and Polio virus, which were added to PC. After photochemical treatment with RB and UV light, residual viral infectivity was titrated using 50% Tissue Culture Infective Dose (TCID50)/ml. This treatment was done with concentration of 50 MUM of RB and different doses of UV light (0.24, 0.48, 0.97, 1.29 J/cm (2)). Platelet quality was assessed by measuring pH, Lactate Dehydrogenase (LDH), MTT assay and cell count after treatments and during 4 days of storage against control groups. RESULTS: Concentration of 50 MUM RB with combination of 1.29 J/cm (2) dose of UV resulted in the highest titer reduction of VSV (4 log 10) and HSV (4.26 log10) and lowest titer reduction of Polio virus (2.6 log10). No significant difference was observed between different doses in comparison with control groups. In all treatment groups, the storage stability of platelets in PC was in the acceptable range in comparison with control group. CONCLUSION: This study indicated that RB/UV treatment was a promising pathogen reduction technique in PC and had limited effects on platelet quality. However, further optimization of this method is necessary to deal with blood-borne viruses like non-enveloped viruses. PMID- 26140183 TI - Cobalt Zinc Ferrite Nanoparticles as a Potential Magnetic Resonance Imaging Agent: An In vitro Study. AB - BACKGROUND: Magnetic Nanoparticles (MNP) have been used for contrast enhancement in Magnetic Resonance Imaging (MRI). In recent years, research on the use of ferrite nanoparticles in T2 contrast agents has shown a great potential application in MR imaging. In this work, Co0.5Zn0.5Fe2O4 and Co0.5Zn0.5Fe2O4-DMSA magnetic nanoparticles, CZF-MNPs and CZF-MNPs-DMSA, were investigated as MR imaging contrast agents. METHODS: Cobalt zinc ferrite nanoparticles and their suitable coating, DMSA, were investigated under in vitro condition. Human prostate cancer cell lines (DU145 and PC3) with bare (uncoated) and coated magnetic nanoparticles were investigated as nano-contrast MR imaging agents. RESULTS: Using T2-weighted MR images identified that signal intensity of bare and coated MNPs was enhanced with increasing concentration of MNPs in water. The values of 1/T2 relaxivity (r2) for bare and coated MNPs were found to be 88.46 and 28.80 (mM (-1) s(-1)), respectively. CONCLUSION: The results show that bare and coated MNPs are suitable as T2-weighted MR imaging contrast agents. Also, the obtained r2/r1 values (59.3 and 50) for bare and coated MNPs were in agreement with the results of other previous relevant works. PMID- 26140184 TI - Release Studies on Ciprofloxacin Loaded Non-ionic Surfactant Vesicles. AB - BACKGROUND: Development of new drug carriers would be an interesting approach if it allowed increased efficacy of antibiotics and a reduction in doses, thus reducing the risk of developing resistance. As with most drug carriers, niosomes have been used to improve the selective delivery and the therapeutic index of antimicrobial agents. METHODS: In this study, different formulation of niosomes containing ciprofloxacin (CPFX), Span (20, 60 or 80), Tween (20, 60 or 80) and cholesterol were prepared by film hydration method. The release of the drug from different formulations was studied by using Franz diffusion cell. The niosomes were further characterized by optical microscopy and particle size analysis, and their antimicrobial activity was evaluated. RESULTS: Size of the niosomes was significantly dependent on the amount of cholesterol and surfactant type and varied from 8.56 to 61.3 MUm. The entrapment efficiency of CPFX niosomes prepared by remote loading was more than 74%. Niosomes composed of Span/Tween 60 provided a higher CPFX release rate than other formulations. The obtained results indicated a diffusion-based mechanism for drug leakage through bilayers. All formulations presented more antibacterial activity as compared to free CPFX solution. CONCLUSION: Niosomal CPFX appears to be a promising approach in the management of bacterial infections, especially ophthalmic ones, and should be further evaluated by in vivo experiments. PMID- 26140185 TI - TP53 Binding to BRCA1 and RAD51 in MCF7 and MDA-MB-468 Breast Cancer Cell Lines In vivo and In vitro. AB - BACKGROUND: Tumour suppressor genes such as TP53, BRCA1 and RAD51 are involved in DNA repair and their malfunctions result in genomic instability and cancer. Wild type (WT) TP53 binds to BRCA1and RAD51 in vivo and in vitro. However, mutated TP53 in tumours can interfere with WT TP53 function. We studied how mutation of TP53 in MDA-MB-468 cell line could affect its binding capacity and interfere with WT TP53 interaction with these DNA repair proteins. METHODS: Binding capacity of mutated TP53 in MDA-MB-468 breast cancer cell line to BRCA1 and RAD51 proteins in comparison to WT TP53 in MCF7 cell line was studied by Immunoprecipitation. In vitro studies were performed by GST-WT p53 pull-down assays in these cell lines to assess the interaction of GST-WT p53 with BRCA1 and RAD51 proteins. RESULTS: The results showed that mutated TP53 in MDA-MB-468 cells interacted with BRCA1 protein in vivo and did not effect WT TP53 binding to this protein in vitro. The Immunoprecipitation assays revealed that the mutated TP53 did not bind to RAD51 in comparison to WT TP53. However, this mutated protein could not interfere with binding of RAD51 to GST-WT p53 in MDA-MB-468 cell line by in vitro experiment. CONCLUSION: It was found that WT TP53 interactions with BRCA1 and RAD51 did not interfere with mutated TP53 in MDA-MB-468 cell line. In addition, RAD51 did not bind to TP53 with R273C mutation in vivo. PMID- 26140186 TI - Maternal Supplementary Folate Intake, Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms and the Risk of Orofacial Cleft in Iranian Children. AB - BACKGROUND: The purpose of this study was to describe the association of MTHFR gene single nucleotide polymorphisms (C677T and A1298C) and maternal supplementary folate intake with orofacial clefts in the Iranian population. METHODS: In this case-control study, peripheral venous blood was taken from 65 patients with orofacial clefts and 215 unaffected controls for DNA extraction and kept in EDTA for further analysis. The genotyping was carried out using Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP) and gel electrophoresis. Data were analyzed using Chi square test and logistic regression tests. RESULTS: Genotype frequencies of 677TT were reported to be 13.5 and 36.1% in controls and CL/P patients, respectively, which showed a significant difference compared to CC as reference (OR=4.118; 95% CI=1.997-8.492; p=0.001). Conversely, 1298CC with frequencies of 10.8 and 12.7% in controls and patients, respectively, showed no significant difference compared to AA (OR=2.359; 95% CI=0.792-7.023; p=0.123). Comparing patients whose mothers did not report the folate supplement intake during pregnancy, to controls, it was observed that lack of folate intake was a predisposing factor for having a child with oral clefts (OR=5/718, p=0.000). CONCLUSION: Children carrying the 677TT variant of the MTHFR gene may have an increased risk of CL/P. In addition, the finding that the risk associated with this allele was obviously higher when the mothers didn't use folic acid, supports the hypothesis that folic acid may play a role in the etiology of CL/P. PMID- 26140187 TI - Evaluation of a Modified DNA Extraction Method for Isolation of Cell-Free Fetal DNA from Maternal Serum. AB - BACKGROUND: Discovery of short cell free fetal DNA (cffDNA) fragments in maternal plasma has created major changes in the field of prenatal diagnosis. The use of cffDNA to set up noninvasive prenatal test is limited due to the low concentration of fetal DNA in maternal plasma therefore, employing a high efficiency extraction method leads to more accurate results. The aim of this study was to evaluate the efficiency of Triton/Heat/Phenol (THP) protocol in comparison with the QIAamp DNA Blood mini Kit for cffDNA purification. METHODS: In order to evaluate the efficiency of THP protocol, DNA of Rhesus D (RhD) negative pregnant women's plasma was collected, then real-time PCR for RHD exon 7 was performed. The Ct value data of real time PCR obtained by two different methods were compared and after delivery serology test on cord blood was done to validate the real time PCR results. RESULTS: The results indicated significant differences between two extraction methods (p=0.001). The mean+/-SD of Ct-value using THP protocol was 33.8+/-1.6 and 36.1+/-2.47 using QIAamp DNA Blood mini Kit. CONCLUSION: Our finding demonstrated that THP protocol was more effective than the QIAamp DNA Blood mini Kits for cffDNA extraction and lead to decrease the false negative results. PMID- 26140188 TI - Development of an Ontology for Periodontitis. AB - BACKGROUND: In the clinical dentists and periodontal researchers' community, there is an obvious demand for a systems model capable of linking the clinical presentation of periodontitis to underlying molecular knowledge. A computer readable representation of processes on disease development will give periodontal researchers opportunities to elucidate pathways and mechanisms of periodontitis. An ontology for periodontitis can be a model for integration of large variety of factors relating to a complex disease such as chronic inflammation in different organs accompanied by bone remodeling and immune system disorders, which has recently been referred to as osteoimmunology. METHODS: Terms characteristic of descriptions related to the onset and progression of periodontitis were manually extracted from 194 review articles and PubMed abstracts by experts in periodontology. We specified all the relations between the extracted terms and constructed them into an ontology for periodontitis. We also investigated matching between classes of our ontology and that of Gene Ontology Biological Process. RESULTS: We developed an ontology for periodontitis called Periodontitis Ontology (PeriO). The pathological progression of periodontitis is caused by complex, multi-factor interrelationships. PeriO consists of all the required concepts to represent the pathological progression and clinical treatment of periodontitis. The pathological processes were formalized with reference to Basic Formal Ontology and Relation Ontology, which accounts for participants in the processes realized by biological objects such as molecules and cells. We investigated the peculiarity of biological processes observed in pathological progression and medical treatments for the disease in comparison with Gene Ontology Biological Process (GO-BP) annotations. The results indicated that peculiarities of Perio existed in 1) granularity and context dependency of both the conceptualizations, and 2) causality intrinsic to the pathological processes. PeriO defines more specific concepts than GO-BP, and thus can be added as descendants of GO-BP leaf nodes. PeriO defines causal relationships between the process concepts, which are not shown in GO-BP. The difference can be explained by the goal of conceptualization: PeriO focuses on mechanisms of the pathogenic progress, while GO-BP focuses on cataloguing all of the biological processes observed in experiments. The goal of conceptualization in PeriO may reflect the domain knowledge where a consequence in the causal relationships is a primary interest. We believe the peculiarities can be shared among other diseases when comparing processes in disease against GO-BP. CONCLUSIONS: This is the first open biomedical ontology of periodontitis capable of providing a foundation for an ontology-based model of aspects of molecular biology and pathological processes related to periodontitis, as well as its relations with systemic diseases. PeriO is available at http://bio-omix.tmd.ac.jp/periodontitis/. PMID- 26140189 TI - The dynamic origins of positive health and wellbeing. AB - The causes of wellbeing and illbeing interact with feedback dynamics resulting in the same set of traits giving rise to a variety of health outcomes (multi finality) and different traits giving rise to the same health outcome (equi finality). As a result, a full understanding of health and its disorders must be in terms of a complex adaptive system of causes, rather than in terms of categorical diagnoses or sets of symptoms. The three domains of person-centered integrative diagnosis (PID) are considered here as interacting components of a complex adaptive system comprised of health status (functioning/wellness versus disability/disorder), experience of health (self-awareness/fulfillment versus misunderstanding/suffering) and contributors to health (protective versus risk factors). The PID domains thereby allow healthcare and health promotion to be understood in terms of measurable components of a complex adaptive system. Three major concepts of health are examined in detail to identify their dynamic origins: Psychological Maturity, Flourishing and Resilience. In humanistic psychology, psychological maturity (i.e. healthy personality, mental wellbeing) involves the development of high self-directedness, high co-operativeness and high self-transcendence, but self-transcendence is nevertheless devalued in individualistic and materialistic cultures except when people must face adversity and ultimate situations like suffering or the threat of death. Psychological Maturity develops through two complementary processes often labeled as Flourishing and Resilience. Flourishing is the development of one's potential to live optimally, especially as the result of favorable circumstances, whereas Resilience is positive adaptation to life despite adverse circumstances. As a result of the complex feedback dynamics between the processes of flourishing and resilience, each person is a unique individual who has a variety of paths for achieving positive health and wellbeing open to him or her. Person-centered health promotion and care can thereby be approached as a creative life project that can be conducted with the assistance of healthcare workers who are both therapeutic allies and well-informed experts. PMID- 26140191 TI - Better together: a community- hospital integrative model of healthcare as a practical solution for providing excellence in endocrinology care in an era of limited resources. AB - BACKGROUND: The demand for endocrinology services is growing worldwide, particularly among minority and underserved populations, mainly due to the rapid global increase of diabetes. The medical education of endocrinologists is a resource consuming process and is mainly hospital-based. Yet, given the chronic nature of endocrine morbidity, the greatest demand for endocrinology services is in the community. However, an isolated endocrinologist cannot cope with the rapid changes in the field. Limited funding of hospital facilities does not allow for the establishment of a freestanding endocrine-center; thus, the Community- Hospital Integrative Model of Healthcare (Co-HIMH) was developed and implemented in an Israeli government hospital and is presented as an approach for achieving excellence in endocrinology care. AIM: To describe the design, function and challenges of the Co-HIMH. MODEL DESCRIPTION: Originally, three pillars: 1) the hospital unit as a regional expertise resource, 2) Co-HIMH endocrine providers participating in both community and hospital services, and 3) integrated information flow between health-care providers, supported the integration between hospital and community networks. RESULTS: The community and hospital endocrine human resources were increased to create attainable and accessible endocrine services in the community and hospital. Collaborative interaction between healthcare providers increased both continuity of care and efficient patient navigation. Endocrine hospital referrals for specialized procedures have grown. Within this area of low socioeconomic status, continued medical endocrine education was conducted introducing state-of-the-art treatments. The essence of these achievements was maintained by continuous training of fellows. During the years that the Co-HIMH operated, it certified 14 % of all endocrinology fellows in Israel. Unresolved issues regarding employee rights and formalization of the Co-HIMH status are significant challenges. CONCLUSIONS: In the era of limited resources and increased healthcare demand, creative infrastructures are required. This article provides a successful example of a preliminary model and proposes future needed modifications. PMID- 26140190 TI - A Time for Action on Health Inequities: Foundations of the 2014 Geneva Declaration on Person- and People-centered Integrated Health Care for All. AB - Global inequalities contribute to marked disparities in health and wellness of human populations. Many opportunities now exist to provide health care to all people in a person- and people-centered way that is effective, equitable, and sustainable. We review these opportunities and the scientific, historical, and philosophical considerations that form the basis for the International College of Person-centered Medicine's 2014 Geneva Declaration on Person- and People-centered Integrated Health Care for All. Using consistent time-series data, we critically examine examples of universal healthcare systems in Chile, Spain, and Cuba. In a person-centered approach to public health, people are recognized to have intrinsic dignity and are treated with respect to encourage their developing health and happiness. A person-centered approach supports the freedom and the responsibility to develop one's life in ways that are personally meaningful and that are respectful of others and the environment in which we live together. Evidence suggests that health care organizations function well when they operate in a person-and people-centered way because that stimulates better coordination, cooperation, and social trust. Health care coverage must be integrated at several interconnected levels in order to be effective, efficient, and fair. To reduce the burden of disease, integration is needed between the people seeking and delivering care, within the social network of each person, across the trajectory of each person's life, among primary caregivers and specialists, and across multiple sectors of society. For integration to succeed across all these levels, it must foster common values and a shared vision of the future. PMID- 26140192 TI - Could the clinical interpretability of subgroups detected using clustering methods be improved by using a novel two-stage approach? AB - BACKGROUND: Recognition of homogeneous subgroups of patients can usefully improve prediction of their outcomes and the targeting of treatment. There are a number of research approaches that have been used to recognise homogeneity in such subgroups and to test their implications. One approach is to use statistical clustering techniques, such as Cluster Analysis or Latent Class Analysis, to detect latent relationships between patient characteristics. Influential patient characteristics can come from diverse domains of health, such as pain, activity limitation, physical impairment, social role participation, psychological factors, biomarkers and imaging. However, such 'whole person' research may result in data-driven subgroups that are complex, difficult to interpret and challenging to recognise clinically. This paper describes a novel approach to applying statistical clustering techniques that may improve the clinical interpretability of derived subgroups and reduce sample size requirements. METHODS: This approach involves clustering in two sequential stages. The first stage involves clustering within health domains and therefore requires creating as many clustering models as there are health domains in the available data. This first stage produces scoring patterns within each domain. The second stage involves clustering using the scoring patterns from each health domain (from the first stage) to identify subgroups across all domains. We illustrate this using chest pain data from the baseline presentation of 580 patients. RESULTS: The new two-stage clustering resulted in two subgroups that approximated the classic textbook descriptions of musculoskeletal chest pain and atypical angina chest pain. The traditional single stage clustering resulted in five clusters that were also clinically recognisable but displayed less distinct differences. CONCLUSIONS: In this paper, a new approach to using clustering techniques to identify clinically useful subgroups of patients is suggested. Research designs, statistical methods and outcome metrics suitable for performing that testing are also described. This approach has potential benefits but requires broad testing, in multiple patient samples, to determine its clinical value. The usefulness of the approach is likely to be context-specific, depending on the characteristics of the available data and the research question being asked of it. PMID- 26140193 TI - Effects of natural and artificial selection on survival of columnar cacti seedlings: the role of adaptation to xeric and mesic environments. AB - Escontria chiotilla, Polaskia chichipe, and Stenocereus pruinosus are species of Mexican columnar cacti that are economically important because of their edible fruits. These species are managed by gathering fruits from the wild, silvicultural management in agroforestry systems, and cultivation in home gardens. Previous studies reported that artificial selection favored individuals that produced larger fruits, which indirectly led to the production of larger seeds and seedlings, with possible effects on survival. We hypothesized that seedlings from managed populations would be larger but more susceptible to xeric conditions than those from wild populations. We evaluated the effects of artificial and natural selection on seedling survival of the three species in wild and managed populations, which were managed with low and high intensity, respectively. We tested seedling performance in gradients of shade (0, 40, and 80%) and humidity (low and high). A GLM of seedling survival showed significant differences among species, shade, and humidity treatments, with each species having environmental requirements associated with their particular adaptations. High humidity decreased seedling survival of all species, and high solar radiation decreased survival of S. pruinosus and P. chichipe. The effect of management type was significant only in S. pruinosus. Significant differences in the initial growth of seedlings among species were detected with ANOVA. In optimal conditions, the hypocotyl and the cotyledons decreased in size and the epicotyl grew, whereas under stress, these structures remained unchanged. The optimum conditions of shade and humidity varied among species and management types. The seedlings of S. pruinosus were the largest and the most susceptible, but in all species, seedlings from managed populations were more susceptible to environmental conditions. Thus, artificial selection influenced the susceptibility of these cacti to xeric environments. PMID- 26140194 TI - Explaining forest productivity using tree functional traits and phylogenetic information: two sides of the same coin over evolutionary scale? AB - Given evidences that diverse ecosystems provide more services than depauperate ones, much attention has now turned toward finding meaningful and operational diversity indices. We ask two questions: (1) Does phylogenetic diversity contain additional information not explained by functional traits? And (2) What are the strength and nature of the correlation between phylogeny and functional traits according to the evolutionary scale considered? We used data from permanent forest plots of northeastern Canada for which these links have been demonstrated and important functional traits identified. We show that the nature of the relationship between traits and phylogeny varies dramatically among traits, but also according to the evolutionary distance considered. The demonstration that different characters show phylogenetic autocorrelation at different evolutionary depths suggests that phylogenetic content of traits may be too crude to determine whether phylogenies contain relevant information. However, our study provides support for the use of phylogenies to assess ecosystem functioning when key functional traits are unavailable. We also highlight a potentially important contribution of phylogenetics for conservation and the study of the impact of biodiversity loss on ecosystem functioning and the provision of services, given the accumulating evidence that mechanisms promoting diversity effects shift over time to involve different traits. PMID- 26140195 TI - Seaweed fails to prevent ocean acidification impact on foraminifera along a shallow-water CO2 gradient. AB - Ocean acidification causes biodiversity loss, alters ecosystems, and may impact food security, as shells of small organisms dissolve easily in corrosive waters. There is a suggestion that photosynthetic organisms could mitigate ocean acidification on a local scale, through seagrass protection or seaweed cultivation, as net ecosystem organic production raises the saturation state of calcium carbonate making seawater less corrosive. Here, we used a natural gradient in calcium carbonate saturation, caused by shallow-water CO2 seeps in the Mediterranean Sea, to assess whether seaweed that is resistant to acidification (Padina pavonica) could prevent adverse effects of acidification on epiphytic foraminifera. We found a reduction in the number of species of foraminifera as calcium carbonate saturation state fell and that the assemblage shifted from one dominated by calcareous species at reference sites (pH ~8.19) to one dominated by agglutinated foraminifera at elevated levels of CO2 (pH ~7.71). It is expected that ocean acidification will result in changes in foraminiferal assemblage composition and agglutinated forms may become more prevalent. Although Padina did not prevent adverse effects of ocean acidification, high biomass stands of seagrass or seaweed farms might be more successful in protecting epiphytic foraminifera. PMID- 26140196 TI - Predicting dispersal of auto-gyrating fruit in tropical trees: a case study from the Dipterocarpaceae. AB - Seed dispersal governs the distribution of plant propagules in the landscape and hence forms the template on which density-dependent processes act. Dispersal is therefore a vital component of many species coexistence and forest dynamics models and is of applied value in understanding forest regeneration. Research on the processes that facilitate forest regeneration and restoration is given further weight in the context of widespread loss and degradation of tropical forests, and provides impetus to improve estimates of seed dispersal for tropical forest trees. South-East Asian lowland rainforests, which have been subject to severe degradation, are dominated by trees of the Dipterocarpaceae family which constitute over 40% of forest biomass. Dipterocarp dispersal is generally considered to be poor given their large, gyration-dispersed fruits. However, there is wide variability in fruit size and morphology which we hypothesize mechanistically underpins dispersal potential through the lift provided to seeds mediated by the wings. We explored experimentally how the ratio of fruit wing area to mass ("inverse wing loading," IWL) explains variation in seed dispersal kernels among 13 dipterocarp species by releasing fruit from a canopy tower. Horizontal seed dispersal distances increased with IWL, especially at high wind speeds. Seed dispersal of all species was predominantly local, with 90% of seed dispersing <10 m, although maximum dispersal distances varied widely among species. We present a generic seed dispersal model for dipterocarps based on attributes of seed morphology and provide modeled seed dispersal kernels for all dipterocarp species with IWLs of 1-50, representing 75% of species in Borneo. PMID- 26140197 TI - Intervarietal and intravarietal genetic structure in Douglas-fir: nuclear SSRs bring novel insights into past population demographic processes, phylogeography, and intervarietal hybridization. AB - Douglas-fir (Pseudotsuga menziesii) is one of numerous wide-range forest tree species represented by subspecies/varieties, which hybridize in contact zones. This study examined the genetic structure of this North American conifer and its two hybridizing varieties, coastal and Rocky Mountain, at intervarietal and intravarietal level. The genetic structure was subsequently associated with the Pleistocene refugial history, postglacial migration and intervarietal hybridization/introgression. Thirty-eight populations from the USA and Canada were genotyped for 13 nuclear SSRs and analyzed with simulations and traditional population genetic structuring methods. Eight genetic clusters were identified. The coastal clusters embodied five refugial populations originating from five distinct refugia. Four coastal refugial populations, three from California and one from western Canada, diverged during the Pleistocene (56.9-40.1 ka). The three Rocky Mountain clusters reflected distinct refugial populations of three glacial refugia. For Canada, ice covered during the Last Glacial Maximum, we present the following three findings. (1) One refugial population of each variety was revealed in the north of the distribution range. Additional research including paleodata is required to support and determine whether both northern populations originated from cryptic refugia situated south or north of the ice covered area. (2) An interplay between intravarietal gene flow of different refugial populations and intervarietal gene flow by hybridization and introgression was identified. (3) The Canadian hybrid zone displayed predominantly introgressants of the Rocky Mountain into the coastal variety. This study provides new insights into the complex Quaternary dynamics of this conifer essential for understanding its evolution (outside and inside the native range), adaptation to future climates and for forest management. PMID- 26140198 TI - Identification of ungulates used in a traditional Chinese medicine with DNA barcoding technology. AB - Horns of Saiga antelope (Saiga tatarica) have always been an ingredient of "Lingyangjiao", a traditional Chinese medicine (TCM). Persistent hunting for Saiga antelope has already threatened the survival of critical endangered populations in wild. To control the growing pressure, CITES and Chinese government have legislated for monitoring the trade of Saiga horns. However, similar ungulate horns are difficult to identify by their morphological characteristics, which has impeded the law enforcement. Besides Saiga antelope, other seven ungulate species which have similar horns are also sold and marked as "Lingyangjiao" in TCM markets to offset shortage of Saiga antelope horns. Such species are Gazella subgutturosa, Pantholops hodgsonii, Procapra picticaudata, Procapra gutturosa, Procapra przewalskii, Capra hircus, and Ovis aries. Our study aimed at implementing DNA barcoding technology to diagnose Saiga horns and the substitutes. We successfully extracted genomic DNA from horn samples. We recovered COI sequences of 644 bp with specific primers and 349 bp with nested PCR primers designed for degraded horn samples. The mean interspecific genetic distance of data set of the 644-bp full barcodes and the 349-bp mini-barcodes was 14.96% and 15.38%, respectively, and the mean intraspecific distance was 0.24% and 0.20%, respectively. Each species formed independent clades in neighbor joining (NJ) phylogenetic tree of the two data sets with >99% supporting values, except P. gutturosa and P. przewalskii. The deep genetic distances gap and clear species clades in NJ tree of either full barcodes or mini-barcodes suggest that barcoding technology is an effective tool to diagnose Saiga horns and their substitutes. Barcoding diagnosis protocol developed here will simplify diagnosis of "Lingyangjiao" species and will facilitate conservation of endangered ungulates involved in TCM "Lingyangjiao" markets, especially the Saiga antelope. PMID- 26140199 TI - Condition, not eyespan, predicts contest outcome in female stalk-eyed flies, Teleopsis dalmanni. AB - In contests among males, body condition is often the key determinant of a successful outcome, with fighting ability signaled by so-called armaments, that is, exaggerated, condition-dependent traits. However, it is not known whether condition and exaggerated traits function in the same way in females. Here, we manipulated adult condition by varying larval nutrition in the stalk-eyed fly, Teleopsis dalmanni, a species in which eyespan is exaggerated in both sexes, and we measured the outcome of contests between females of similar or different body condition and relative eyespan. We found that females in higher condition, with both larger bodies and eyespan, won a higher proportion of encounters when competing against rivals of lower condition. However, when females were of equal condition, neither eyespan nor body length had an effect on the outcome of a contest. An analysis of previously published data revealed a similar pattern in males: individuals with large relative eyespan did not win significantly more encounters when competing with individuals of a similar body size. Contrary to expectations, and to previous findings in males, there was no clear effect of differences in body size or eyespan affecting contest duration in females. Taken together, our findings suggest that although eyespan can provide an honest indicator of condition, large eyespans provide no additional benefit to either sex in intrasexual aggressive encounters; body size is instead the most important factor. PMID- 26140200 TI - Ecological gradients driving the distribution of four Ericaceae in boreal Quebec, Canada. AB - Understory species play a significant role in forest ecosystem dynamics. As such, species of the Ericaceae family have a major effect on the regeneration of tree species in boreal ecosystems. It is thus imperative to understand the ecological gradients controlling their distribution and abundance, so that their impacts can be taken into account in sustainable forest management. Using innovative analytical techniques from landscape ecology, we aimed to position, along ecological gradients, four Ericaceae found in the boreal forest of Quebec (Canada) (Rhododendron groenlandicum, Kalmia angustifolia, Chamaedaphne calyculata, and Vaccinium spp), to regionalize these species into landscape units relevant to forest management, and to estimate the relative importance of several ecological drivers (climate, disturbances, stand attributes, and physical environment) that control the species distribution and abundance. We conducted our study in boreal Quebec, over a study area covering 535,355 km(2). We used data from 15,339 ecological survey plots and forest maps to characterize 1422 ecological districts covering the study region. We evaluated the relative proportion of each ericaceous species and explanatory variables at the district level. Vegetation and explanatory variables matrices were used to conduct redundancy, cluster, and variation partitioning analyses. We observed that ericaceous species are mainly distributed in the western part of the study area and each species has a distinct latitudinal and longitudinal gradient distribution. On the basis of these gradients, we delimited 10 homogeneous landscape units distinct in terms of ericaceous species abundance and environmental drivers. The distribution of the ericaceous species along ecological gradients is closely related to the overlaps between the four sets of explanatory variables considered. We conclude that the studied Ericaceae occupy specific positions along ecological gradients and possess a specific abundance and distribution controlled by the integration of multiple explanatory variables. PMID- 26140201 TI - When is it worth being a self-compatible hermaphrodite? Context-dependent effects of self-pollination on female advantage in gynodioecious Silene nutans. AB - In gynodioecious plant species with nuclear-cytoplasmic sex determination, females and hermaphrodites plants can coexist whenever female have higher seed fitness than hermaphrodites. Although the effect of self fertilization on seed fitness in hermaphrodites has been considered theoretically, this effect is far from intuitive, because it can either increase the relative seed fitness of the females (if it leads hermaphrodites to produce inbred, low quality offspring) or decrease it (if it provides reproductive assurance to hermaphrodites). Hence, empirical investigation is needed to document whether relative seed fitness varies with whether pollen is or is not limiting to seed production. In the current study, we measured fruit set and seed production in both females and hermaphrodites and the selfing rate in hermaphrodites in two experimental patches that differed in sex ratios in the gynodioecious plant Silene nutans. We found an impact of plant gender, patch, and their interaction, with females suffering from stronger pollen limitation when locally frequent. In the most pollen-limited situation, the selfing rate of hermaphrodites increased and provided hermaphrodites with a type of reproductive assurance that is not available to females. By integrating both the beneficial (reproductive assurance) and costly effects (through inbreeding depression) of self-pollination, we showed that whether females did or did not exhibit higher seed fitness depended on the degree of pollen limitation on seed production. PMID- 26140202 TI - Timing of flowering and intensity of attack by a butterfly herbivore in a polyploid herb. AB - Timing of plant development both determines the abiotic conditions that the plant experiences and strongly influences the intensity of interactions with other organisms. Plants and herbivores differ in their response to environmental cues, and spatial and temporal variation in environmental conditions might influence the synchrony between host plants and herbivores, and the intensity of their interactions. We investigated whether differences in first day of flowering among and within 21 populations of the polyploid herb Cardamine pratensis influenced the frequency of oviposition by the butterfly Anthocharis cardamines during four study years. The proportion of plants that became oviposited upon differed among populations, but these differences were not related to mean flowering phenology within the population in any of the four study years. Attack rates in the field were also not correlated with resistance to oviposition estimated under controlled conditions. Within populations, the frequency of butterfly attack was higher in early-flowering individuals in two of the four study years, while there was no significant relationship in the other 2 years. Larger plants were more likely to become oviposited upon in all 4 years. The effects of first flowering day and size on the frequency of butterfly attack did not differ among populations. The results suggest that differences in attack intensities among populations are driven mainly by differences in the environmental context of populations while mean differences in plant traits play a minor role. The fact that within populations timing of flowering influenced the frequency of herbivore attack only in some years and suggests that herbivore-mediated selection on plant phenology differs among years, possibly because plants and herbivores respond differently to environmental cues. PMID- 26140203 TI - Indirect selection of thermal tolerance during experimental evolution of Drosophila melanogaster. AB - Natural selection alters the distribution of a trait in a population and indirectly alters the distribution of genetically correlated traits. Long standing models of thermal adaptation assume that trade-offs exist between fitness at different temperatures; however, experimental evolution often fails to reveal such trade-offs. Here, we show that adaptation to benign temperatures in experimental populations of Drosophila melanogaster resulted in correlated responses at the boundaries of the thermal niche. Specifically, adaptation to fluctuating temperatures (16-25 degrees C) decreased tolerance of extreme heat. Surprisingly, flies adapted to a constant temperature of 25 degrees C had greater cold tolerance than did flies adapted to other thermal conditions, including a constant temperature of 16 degrees C. As our populations were never exposed to extreme temperatures during selection, divergence of thermal tolerance likely reflects indirect selection of standing genetic variation via linkage or pleiotropy. We found no relationship between heat and cold tolerances in these populations. Our results show that the thermal niche evolves by direct and indirect selection, in ways that are more complicated than assumed by theoretical models. PMID- 26140204 TI - Warming experiments elucidate the drivers of observed directional changes in tundra vegetation. AB - Few studies have clearly linked long-term monitoring with in situ experiments to clarify potential drivers of observed change at a given site. This is especially necessary when findings from a site are applied to a much broader geographic area. Here, we document vegetation change at Barrow and Atqasuk, Alaska, occurring naturally and due to experimental warming over nearly two decades. An examination of plant cover, canopy height, and community indices showed more significant differences between years than due to experimental warming. However, changes with warming were more consistent than changes between years and were cumulative in many cases. Most cases of directional change observed in the control plots over time corresponded with a directional change in response to experimental warming. These included increases in canopy height and decreases in lichen cover. Experimental warming resulted in additional increases in evergreen shrub cover and decreases in diversity and bryophyte cover. This study suggests that the directional changes occurring at the sites are primarily due to warming and indicates that further changes are likely in the next two decades if the regional warming trend continues. These findings provide an example of the utility of coupling in situ experiments with long-term monitoring to accurately document vegetation change in response to global change and to identify the underlying mechanisms driving observed changes. PMID- 26140205 TI - Seasonal cycles, phylogenetic assembly, and functional diversity of orchid bee communities. AB - Neotropical rainforests sustain some of the most diverse terrestrial communities on Earth. Euglossine (or orchid) bees are a diverse lineage of insect pollinators distributed throughout the American tropics, where they provide pollination services to a staggering diversity of flowering plant taxa. Elucidating the seasonal patterns of phylogenetic assembly and functional trait diversity of bee communities can shed new light into the mechanisms that govern the assembly of bee pollinator communities and the potential effects of declining bee populations. Male euglossine bees collect, store, and accumulate odoriferous compounds (perfumes) to subsequently use during courtship display. Thus, synthetic chemical baits can be used to attract and monitor euglossine bee populations. We conducted monthly censuses of orchid bees in three sites in the Magdalena valley of Colombia - a region where Central and South American biotas converge - to investigate the structure, diversity, and assembly of euglossine bee communities through time in relation to seasonal climatic cycles. In particular, we tested the hypothesis that phylogenetic community structure and functional trait diversity changed in response to seasonal rainfall fluctuations. All communities exhibited strong to moderate phylogenetic clustering throughout the year, with few pronounced bursts of phylogenetic overdispersion that coincided with the transition from wet-to-dry seasons. Despite the heterogeneous distribution of functional traits (e.g., body size, body mass, and proboscis length) and the observed seasonal fluctuations in phylogenetic diversity, we found that functional trait diversity, evenness, and divergence remained constant during all seasons in all communities. However, similar to the pattern observed with phylogenetic diversity, functional trait richness fluctuated markedly with rainfall in all sites. These results emphasize the importance of considering seasonal fluctuations in community assembly and provide a glimpse to the potential effects that climatic alterations may have on both pollinator communities and the ecosystem services they provide. PMID- 26140206 TI - Local and global pyrogeographic evidence that indigenous fire management creates pyrodiversity. AB - Despite the challenges wildland fire poses to contemporary resource management, many fire-prone ecosystems have adapted over centuries to millennia to intentional landscape burning by people to maintain resources. We combine fieldwork, modeling, and a literature survey to examine the extent and mechanism by which anthropogenic burning alters the spatial grain of habitat mosaics in fire-prone ecosystems. We survey the distribution of Callitris intratropica, a conifer requiring long fire-free intervals for establishment, as an indicator of long-unburned habitat availability under Aboriginal burning in the savannas of Arnhem Land. We then use cellular automata to simulate the effects of burning identical proportions of the landscape under different fire sizes on the emergent patterns of habitat heterogeneity. Finally, we examine the global extent of intentional burning and diversity of objectives using the scientific literature. The current distribution of Callitris across multiple field sites suggested long unburnt patches are common and occur at fine scales (<0.5 ha), while modeling revealed smaller, patchy disturbances maximize patch age diversity, creating a favorable habitat matrix for Callitris. The literature search provided evidence for intentional landscape burning across multiple ecosystems on six continents, with the number of identified objectives ranging from two to thirteen per study. The fieldwork and modeling results imply that the occurrence of long-unburnt habitat in fire-prone ecosystems may be an emergent property of patch scaling under fire regimes dominated by smaller fires. These findings provide a model for understanding how anthropogenic burning alters spatial and temporal aspects of habitat heterogeneity, which, as the literature survey strongly suggests, warrant consideration across a diversity of geographies and cultures. Our results clarify how traditional fire management shapes fire-prone ecosystems, which despite diverse objectives, has allowed human societies to cope with fire as a recurrent disturbance. PMID- 26140207 TI - Elevation as a barrier: genetic structure for an Atlantic rain forest tree (Bathysa australis) in the Serra do Mar mountain range, SE Brazil. AB - Distance and discrete geographic barriers play a role in isolating populations, as seed and pollen dispersal become limited. Nearby populations without any geographic barrier between them may also suffer from ecological isolation driven by habitat heterogeneity, which may promote divergence by local adaptation and drift. Likewise, elevation gradients may influence the genetic structure and diversity of populations, particularly those marginally distributed. Bathysa australis (Rubiaceae) is a widespread tree along the elevation gradient of the Serra do Mar, SE Brazil. This self-compatible species is pollinated by bees and wasps and has autochoric seeds, suggesting restricted gene dispersal. We investigated the distribution of genetic diversity in six B. australis populations at two extreme sites along an elevation gradient: a lowland site (80 216 m) and an upland site (1010-1100 m.a.s.l.). Nine microsatellite loci were used to test for genetic structure and to verify differences in genetic diversity between sites. We found a marked genetic structure on a scale as small as 6 km (F ST = 0.21), and two distinct clusters were identified, each corresponding to a site. Although B. australis is continuously distributed along the elevation gradient, we have not observed a gene flow between the extreme populations. This might be related to B. australis biological features and creates a potential scenario for adaptation to the different conditions imposed by the elevation gradient. We failed to find an isolation-by-distance pattern; although on the fine scale, all populations showed spatial autocorrelation until ~10-20 m. Elevation difference was a relevant factor though, but we need further sampling effort to check its correlation with genetic distance. The lowland populations had a higher allelic richness and showed higher rare allele counts than the upland ones. The upland site may be more selective, eliminating rare alleles, as we did not find any evidence for bottleneck. PMID- 26140209 TI - Bovine congenital erythropoietic protoporphyria in a crossbred limousin heifer in Ireland. AB - An unusual case of an 11-month-old, black Limousin-cross heifer, with an 8-month history of episodic seizures and photosensitisation, was referred by a veterinary practitioner to the Farm Animal Section of the UCD Veterinary Hospital, School of Veterinary Medicine, University College Dublin, Ireland, in August 2014. Following an investigation, a diagnosis of Bovine Congenital Erythropoietic Protoporphyria (BCEPP) was made. To the authors' knowledge this is the first report of such a case in Ireland. BCEPP should be considered as a differential diagnosis in young animals displaying periodic seizures and/or photosensitisation. PMID- 26140210 TI - The Drosophila homologue of Rootletin is required for mechanosensory function and ciliary rootlet formation in chordotonal sensory neurons. AB - BACKGROUND: In vertebrates, rootletin is the major structural component of the ciliary rootlet and is also part of the tether linking the centrioles of the centrosome. Various functions have been ascribed to the rootlet, including maintenance of ciliary integrity through anchoring and facilitation of transport to the cilium or at the base of the cilium. In Drosophila, Rootletin function has not been explored. RESULTS: In the Drosophila embryo, Rootletin is expressed exclusively in cell lineages of type I sensory neurons, the only somatic cells bearing a cilium. Expression is strongest in mechanosensory chordotonal neurons. Knock-down of Rootletin results in loss of ciliary rootlet in these neurons and severe disruption of their sensory function. However, the sensory cilium appears largely normal in structure and in localisation of proteins suggesting no strong defect in ciliogenesis. No evidence was found for a defect in cell division. CONCLUSIONS: The role of Rootletin as a component of the ciliary rootlet is conserved in Drosophila. In contrast, lack of a general role in cell division is consistent with lack of centriole tethering during the centrosome cycle in Drosophila. Although our evidence is consistent with an anchoring role for the rootlet, severe loss of mechanosensory function of chordotonal (Ch) neurons upon Rootletin knock-down may suggest a direct role for the rootlet in the mechanotransduction mechanism itself. PMID- 26140211 TI - In conversation with...John Burnard West. PMID- 26140212 TI - Building a multi-scaled geospatial temporal ecology database from disparate data sources: fostering open science and data reuse. AB - Although there are considerable site-based data for individual or groups of ecosystems, these datasets are widely scattered, have different data formats and conventions, and often have limited accessibility. At the broader scale, national datasets exist for a large number of geospatial features of land, water, and air that are needed to fully understand variation among these ecosystems. However, such datasets originate from different sources and have different spatial and temporal resolutions. By taking an open-science perspective and by combining site based ecosystem datasets and national geospatial datasets, science gains the ability to ask important research questions related to grand environmental challenges that operate at broad scales. Documentation of such complicated database integration efforts, through peer-reviewed papers, is recommended to foster reproducibility and future use of the integrated database. Here, we describe the major steps, challenges, and considerations in building an integrated database of lake ecosystems, called LAGOS (LAke multi-scaled GeOSpatial and temporal database), that was developed at the sub-continental study extent of 17 US states (1,800,000 km(2)). LAGOS includes two modules: LAGOSGEO, with geospatial data on every lake with surface area larger than 4 ha in the study extent (~50,000 lakes), including climate, atmospheric deposition, land use/cover, hydrology, geology, and topography measured across a range of spatial and temporal extents; and LAGOSLIMNO, with lake water quality data compiled from ~100 individual datasets for a subset of lakes in the study extent (~10,000 lakes). Procedures for the integration of datasets included: creating a flexible database design; authoring and integrating metadata; documenting data provenance; quantifying spatial measures of geographic data; quality-controlling integrated and derived data; and extensively documenting the database. Our procedures make a large, complex, and integrated database reproducible and extensible, allowing users to ask new research questions with the existing database or through the addition of new data. The largest challenge of this task was the heterogeneity of the data, formats, and metadata. Many steps of data integration need manual input from experts in diverse fields, requiring close collaboration. PMID- 26140213 TI - SMAP: a streamlined methylation analysis pipeline for bisulfite sequencing. AB - BACKGROUND: DNA methylation has important roles in the regulation of gene expression and cellular specification. Reduced representation bisulfite sequencing (RRBS) has prevailed in methylation studies due to its cost effectiveness and single-base resolution. The rapid accumulation of RRBS data demands well designed analytical tools. FINDINGS: To streamline the data processing of DNA methylation from multiple RRBS samples, we present a flexible pipeline named SMAP, whose features include: (i) handling of single-and/or paired end diverse bisulfite sequencing data with reduced false-positive rates in differentially methylated regions; (ii) detection of allele-specific methylation events with improved algorithms; (iii) a built-in pipeline for detection of novel single nucleotide polymorphisms (SNPs); (iv) support of multiple user-defined restriction enzymes; (v) conduction of all methylation analyses in a single-step operation when well configured. CONCLUSIONS: Simulation and experimental data validated the high accuracy of SMAP for SNP detection and methylation identification. Most analyses required in methylation studies (such as estimation of methylation levels, differentially methylated cytosine groups, and allele specific methylation regions) can be executed readily with SMAP. All raw data from diverse samples could be processed in parallel and 'packetized' streams. A simple user guide to the methylation applications is also provided. PMID- 26140214 TI - "Boring" family routines reduce non-communicable diseases: a commentary and call for action. AB - As global donors shift their efforts from infectious diseases to non-communicable diseases (NCD), it is critical to capitalize on our prior mistakes and successes. Policy makers and public health administrators are often looking for magic bullets: drugs or treatments to eradicate disease. Yet, each potential magic bullet requires consistent, daily implementation and adherence to a new set of habits to actually work. Families' and communities' daily, interlocking routines will be the battlefield on which scientific and technological breakthroughs will be implemented and succeed or not. Currently, there are many evidence-based interventions (EBI) which have been demonstrated to shift specific habits which account for most NCD (eating, drinking, moving, and smoking). Yet, securing sustained uptake of these programs is rare - suggesting different intervention strategies are needed. Structural changes, policy nudges, and partnerships with private enterprise may be able to shift the health behaviors of more citizens faster and at a lower cost than existing EBI. Addressing concurrent risk and protective factors at the community level and intervening to shape new cultural routines may be useful to reduce NCD. PMID- 26140215 TI - Comparative effects of Facebook and conventional media on body image dissatisfaction. AB - BACKGROUND: Appearance comparison has consistently been shown to engender body image dissatisfaction. To date, most studies have demonstrated this relationship between appearance comparison and body image dissatisfaction in the context of conventional media images depicting the thin-ideal. Social comparison theory posits that people are more likely to compare themselves to similar others. Since social media forums such as Facebook involve one's peers, the current study aimed to determine whether the relationship between appearance comparison and body image dissatisfaction would be stronger for those exposed to social media images, compared to conventional media images. METHODS: A sample of 193 female first year university students were randomly allocated to view a series of either Facebook or conventional media thin-ideal images. Participants completed questionnaires assessing pre- and post- image exposure measures of thin-ideal internalisation, appearance comparison, self-esteem, Facebook use and eating disorder risk. RESULTS: Type of exposure was not found to moderate the relationship between appearance comparison and changes in body image dissatisfaction. When analysed according to exposure type, appearance comparison only significantly predicted body image dissatisfaction change for those exposed to Facebook, but not conventional media. Facebook use was found to predict higher baseline body image dissatisfaction and was associated with higher eating disorder risk. CONCLUSIONS: The findings suggest the importance of extending the body image dissatisfaction literature by taking into account emerging social media formats. It is recommended that interventions for body image dissatisfaction and eating disorders consider appearance comparison processes elicited by thin-ideal content on social media forums, such as Facebook, in addition to conventional media. PMID- 26140216 TI - FIRST STEPS - a randomized controlled trial on the evaluation of the implementation and effectiveness of two early prevention programs for promoting the social integration and a healthy development of children with an immigrant background from 0-3. AB - BACKGROUND: The social integration of children with an immigrant background has become one of the most urgent social responsibilities in Germany. They are more likely to live in high-risk environments and are disadvantaged with respect to health related variables as well as educationally. Quite a number of projects supporting their integration into the German society exist although many are hardly scientifically evaluated. Most of them focus on the acquisition of German language and therefore address older children (and adults). However, international experts agree that social integration is not only a matter of language but also of earlier developmental processes of children in their first months of life connected to adequate early parenting. METHODS/DESIGN: The model project FIRST STEPS focuses on earliest prevention for children with an immigrant background, supporting their parents in the critical phase of migration and early parenthood. In a prospective randomized comparison group design the effectiveness of a psychoanalytically oriented early prevention program (intervention A) is compared to the outcomes of groups offered by paraprofessionals with an immigrant background (intervention B). Intervention A is a professional offer supporting immigrant families based on developmental psychological and on knowledge on early parenting. 180 families are randomly assigned to intervention A or B. They are supported during the first 3 years of the children's lives. Social and family stressors, the quality of the parent-child-interaction, child attachment security, the affective, cognitive and social-emotional development of the children and the social integration of the families are assessed during and after the intervention. DISCUSSION: The project aims at evaluating the implementation as well as the short- and long-term effectiveness of psychoanalytically oriented intervention A compared to the outcomes of intervention B. It is expected that professionally supported early parenting (intervention A) improves the social emotional, cognitive and language development of immigrant children as well as the social integration of their families to a greater extent than in the comparison groups. In case the model project proves to be effective, a rollout across Germany is possible. Due to the "difficult-to-reach" immigrant families challenges in recruitment, uptake and retention of participants are anticipated. TRIAL REGISTRATION: DRKS-ID: DRKS00004632, trial registration date: 05.02.2013. PMID- 26140217 TI - BAP1 hereditary cancer predisposition syndrome: a case report and review of literature. AB - A 72-year-old woman was diagnosed with uveal melanoma, peritoneal mesothelioma and a primary biliary tract adenocarcinoma. She had a strong family history of mesothelioma as well as other malignancies including renal cell carcinoma. The recently described BAP1 hereditary cancer predisposition syndrome was suspected, but immunohistochemical labeling was not conclusive. Genetic testing confirmed a novel and unusual germline mutation in the ubiquitin hydrolase domain of the BAP1 gene (p.Tyr173Cys) and the patient was diagnosed with the BAP1 hereditary cancer predisposition syndrome. This case demonstrates the importance of clinically recognizing this rare syndrome and its manifestations, some which are still being characterized. It also highlights the importance of genetic testing in cases where there is a high clinical suspicion, even when screening tests, such as immunohistochemistry, in this case, are inconclusive. The diagnosis of a germline BAP1 mutation may have important implications for both the patient and their families with regards to further genetic testing and active surveillance programs. Further research is needed to fully understand the extent and clinical implications of this rare cancer syndrome. PMID- 26140218 TI - The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin. AB - BACKGROUND: T-2 toxin poses a great threat to human health because it has the highest toxicity of the currently known trichothecene mycotoxins. To understand the in vivo toxicity and transformation mechanism of T-2 toxin, we investigated the role of one kind of principal phase I drug-metabolizing enzymes (cytochrome P450 [CYP450] enzymes) on the metabolism of T-2 toxin, which are crucial to the metabolism of endogenous substances and xenobiotics. We also investigated carboxylesterase, which also plays an important role in the metabolism of toxic substances. METHODS: A chemical inhibition method and a recombinant method were employed to investigate the metabolism of the T-2 toxin by the CYP450 enzymes, and a chemical inhibition method was used to study carboxylesterase metabolism. Samples incubated with human liver microsomes were analyzed by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC- QqQ MS) after a simple pretreatment. RESULTS: In the presence of a carboxylesterase inhibitor, only 20 % T-2 toxin was metabolized. When CYP enzyme inhibitors and a carboxylesterase inhibitor were both present, only 3 % of the T-2 toxin was metabolized. The contributions of the CYP450 enzyme family to T-2 toxin metabolism followed the descending order CYP3A4, CYP2E1, CYP1A2, CYP2B6 or CYP2D6 or CYP2C19. CONCLUSION: Carboxylesterase and CYP450 enzymes are of great importance in T-2 toxin metabolism, in which carboxylesterase is predominant and CYP450 has a subordinate role. CYP3A4 is the principal member of the CYP450 enzyme family responsible for T-2 toxin metabolism. The primary metabolite produced by carboxylesterase is HT-2, and the main metabolite produced by CYP 3A4 is 3'-OH T-2. The different metabolites show different toxicities. Our results will provide useful data concerning the toxic mechanism, the safety evaluation, and the health risk assessment of T-2 toxin. PMID- 26140219 TI - Improved adipogenic in vitro differentiation: comparison of different adipogenic cell culture media on human fat and bone stroma cells for fat tissue engineering. AB - To date there is no sufficient in vitro fat tissue engineering and a protocol has not been well established for this purpose. Therefore, we evaluated the in vitro influence of two different adipogenic growth media for their stimulation potential on different cell lineages to clearly define the most potent adipogenic growth media for future in vitro tissue engineering approaches. The samples for differentiation were composed of human adipogenic-derived stroma cells (hADSCs) and human bone marrow mesenchymal stroma cells (hMSCs). A normal adipogenic medium (NAM) and a specific adipogenic medium (SAM) were tested for their adipogenic stimulation potential. After 10 days and 21 days the relative gene expression was measured for the adipogenic marker genes PPARgamma2, C/EBPalpha, FABP4, LPL, and GLUT4 detected through real time reverse transcriptase polymease chain reaction (RT-PCR). Other study variables were the comparison between NAM and SAM and between the used cells hADSCs and hMSCs. Additionally an Oil-Red staining was performed after 21 days. Our results revealed that only SAM was significantly (P<0.05) superior in the differentiation process in contrast to NAM for 10 days and 21 days. As well was SAM superior to differentiate the used cell lineages. This was evaluated by the detected marker genes PPARgamma2, C/EBPalpha, FABP4, LPL, and GLUT4 through real time RT-PCR and by Oil-Red staining. In addition, the hMSCs proofed to be equal donor cells for adipogenic differentiation especially when stimulated by SAM. The results suggest that the SAM should be established as a new standard medium for a more promising in vitro adipogenic differentiation. PMID- 26140220 TI - A single fraction from Uncaria sinensis exerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons. AB - We identified a neuroprotective single fraction among 62 ones of hexane extract from Uncaria sinensis (JGH43IA) and investigated its effects and mechanisms in primary cortical neurons. Pretreatment with JGH43IA showed a significantly increase cell viability in a dose-dependent manner with a decrease in the lactate dehydrogenase release. When we performed morphological assay and flow cytometry to determination of the type of cell death, pretreatment with JGH43IA showed a significant reduction of glutamate-induced apoptotic cell death. Then we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation to elucidate possible pathways of neuroprotection by JGH43IA. Pretreatment with JGH43IA exhibited a significant attenuation of NMDAR GluN2B subunit activation and a decrease in active form of calpain 1 leading to subsequent cleavage of striatal-enriched protein tyrosine phosphatase (STEP). In addition, pretreatment with JGH43IA showed a marked increase of cAMP responsive element binding protein. These results suggest that JGH43IA may have neuroprotective effects through down-regulation of NMDAR GluN2B subunit and calpain 1 activation, and subsequent alleviation of STEP cleavage. This single fraction from U. sinensis might be a useful therapeutic agent for brain disorder associated with glutamate injury. PMID- 26140221 TI - The effects of repetitive transcranial magnetic stimulation on proliferation and differentiation of neural stem cells. AB - Repetitive transcranial magnetic stimulation (rTMS) is a new method for treating many neurological conditions; however, the exact therapeutic mechanisms behind rTMS-induced plasticity are still unknown. Neural stem and progenitor cells (NS/PCs) are active players in brain regeneration and plasticity but their behavior in the context of rTMS therapy needs further elucidation. We aimed to evaluate the effects of rTMS on proliferation and differentiation of NS/PCs in the subventricular zone (SVZ) of adult mouse brain. Adult male mice (n=30) were divided into rTMS (1-Hz and 30-Hz) and sham groups and treated for 7 or 14 consecutive days. Harvested NS/PCs from the SVZ were cultured in the neurosphere assay for 8 days and the number and size of the resulting neurospheres as well as their in vitro differentiation capacity were evaluated. After one week of rTMS treatment at 1-Hz and 30-Hz compared with sham stimulation, the mean neurosphere forming frequency per brain was not different while this measure significantly increased after two weeks (P<0.05). The mean neurosphere diameter in 1-Hz treatment paradigm was significantly larger compared with sham stimulation at both 1 and 2 weeks. In contrast, 30-Hz treatment paradigm resulted in significantly larger neurospheres only after 2 weeks. Importantly, rTMS treatment at both frequencies increased neuronal differentiation of the harvested NS/PCs. Furthermore, one week in vitro rTMS treatment of NS/PCs with both 1-Hz and 30-Hz increased NS/PCs proliferation and neuronal differentiation. It is concluded that both 1-Hz and 30-Hz rTMS treatment increase NS/PCs proliferation and neuronal differentiation. PMID- 26140222 TI - Composite nerve fibers in the hypogastric and pelvic splanchnic nerves: an immunohistochemical study using elderly cadavers. AB - To determine the proportion of nerve fibers in the hypogastric nerve (HGN) and pelvic splanchnic nerve (PSN), small tissue strips of the HGN and PSN from 12 donated elderly cadavers were examined histologically. Immunohistochemistry for neuronal nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH) was performed. More than 70% of fibers per bundle in the HGN were positive for TH at the level of the sacral promontory. In addition, NOS- (negative) and/or VIP+ (positive) fibers were observed in small areas of each nerve bundle, although the proportion of each was usually less than 10%. In the PSN near the third sacral nerve root, the proportion of nerve fibers positive for NOS and/or VIP (or TH) was below 30%. In both the HGN and PSN, the number of VIP+ fibers was usually greater than that of NOS+ fibers, with frequent co localization of NOS and VIP. More fibers in both nerves were positive for TH than for these other markers. In contrast to pelvic plexus branches, there were no differences in the proportions of NOS+ and VIP+ fibers between nerve bundles in each of the tissue strips. Thus, target-dependent sorting of nerve fibers was not apparent in the HGN at the level of the sacral promontory or in the PSN near the third sacral nerve root. The NOS+ and/or VIP+ fibers in the HGN were most likely ascending postganglionic fibers to the colon, while those in the PSN root may be preganglionic fibers from Onuf's nucleus. PMID- 26140223 TI - Development of myenteric plexus in human foetuses: a quantitative study. AB - Maturation of neurons of the myenteric plexus (MP) of human fetal sigmoid colon was studied at various weeks of gestation (WG). There is abundant literature on the development of MP in various segments of the gut but there are fewer reports on the development of MP in human sigmoid colon which is a site of various disorders. Sigmoid colonic segments from 12 aborted foetuses aged 14-23WG were processed for NADPH histochemistry. Stereologic evaluation of the neuronal cell profiles, numerical density, number of neurons per ganglion and myenteric fraction was conducted using using imageJ software. According to gestational age, foetuses were assigned into two groups (group 1 [n=7], less than <17WG and group 2 [n=5], more than >17WG). The overall size of neuronal cell profiles in the MP was significantly increased (P<0.05). The numerical density of neurons decreased in group 2 in comparison to group 1, the number of neurons per ganglion and myenteric fraction were increased in group 2 but all these were not statistically significant. This study revealed that the maturational event increases after 17WG and extensive innervations is established at 23WG. During prenatal life there is an increase in the neuronal cell size from 14-23WG signifying maturational process. Such studies are essential for clinicians and surgeons to correlate the normal and pathologic development of the enteric nervous system. PMID- 26140224 TI - Topography of human ankle joint: focused on posterior tibial artery and tibial nerve. AB - Most of foot pain occurs by the entrapment of the tibial nerve and its branches. Some studies have reported the location of the tibial nerve; however, textbooks and researches have not described the posterior tibial artery and the relationship between the tibal nerve and the posterior tibial artery in detail. The purpose of this study was to analyze the location of neurovascular structures and bifurcations of the nerve and artery in the ankle region based on the anatomical landmarks. Ninety feet of embalmed human cadavers were examined. All measurements were evaluated based on a reference line. Neurovascular structures were classified based on the relationship between the tibial nerve and the posterior tibial artery. The bifurcation of arteries and nerves were expressed by X- and Y-coordinates. Based on the reference line, 9 measurements were examined. The most common type I (55.6%), was the posterior tibial artery located medial to the tibial nerve. Neurovascular structures were located less than 50% of the distance between M and C from M at the reference line. The bifurcation of the posterior tibial artery was 41% in X-coordinate, -38% in Y-coordinate, and that of the tibial nerve was 48%, and -10%, respectively. Thirteen measurements and classification showed statistically significant differences between both sexes (P<0.05). It is determined the average position of neurovascular structures in the human ankle region and recorded the differences between the sexes and amongst the populations. These results would be helpful for the diagnosis and treatment of foot pain. PMID- 26140225 TI - Perception of MBBS students to "flipped class room" approach in neuroanatomy module. AB - A flipped classroom is a learner centered approach in which the learner is responsible to attend the class with basic understanding of the subject to fully participate and engage in discussions. The aim of this study was to evaluate students' perception of flipped classroom approach for neuroanatomy module and assess the impact on their performance and attitudes. The subject chosen to evaluate the flipped classroom model for first year medical students was clinical neuroanatomy. One hundred and thirty first year medical students participated in the study module. Students were divided into five groups and five case scenarios pertaining to various clinically relevant regions of the neuraxis, with varying anatomical complexity were generated. The pre- and post-tests were designed to specifically test the declared learning objectives of the session. The perception of the students regarding this model of teaching and learning was also evaluated. Eighty-six percent of students felt that the flipped classroom approach was better at fulfilling the stated learning objectives than the conventional didactic teaching, 92% felt that the work-sheet with questions provided prior to the class enabled a better understanding of the subject and 87% were of the opinion that the web sources with references kindled a greater interest to read as compared with didactic lectures. The paired t test showed highly significant differences between the pre and post-test scores. Student response to the flipped classroom structure was largely positive, indicating it to be an approach worth pursuing in future years. PMID- 26140226 TI - Dual left anterior interventricular coronary artery with a rare course in a Korean. AB - Dual left anterior interventricular coronary artery (also called left anterior descending artery, hereafter referred as LAD) is a rare congenital coronary artery anomaly. Notably, type IV dual LAD has never been reported in Koreans. During a routine dissection, a new variant of type IV dual LAD was found in a 57 year-old Korean male cadaver, whose cause of death was unknown. One LAD originated from the right coronary artery, coursed through the anterior interventricular sulcus, but did not reach the apex cordis. The other LAD arose from the left coronary artery, never entered the anterior interventricular sulcus through its course, but reached the apex cordis, where it met the posterior interventricular branch of the right coronary artery. This is the first report on a new variant of type IV dual LAD in Koreans, which is of clinical importance during procedures containing the coronary artery. PMID- 26140227 TI - Multiple variations in the branches of the coeliac trunk. AB - Here we present a unique case of variation in the branching pattern of the coeliac trunk. In the present case, the coeliac trunk was replaced by two separate arterial trunks. The first arterial trunk bifurcated into the left gastric and the left hepatic arteries. The second arterial trunk bifurcated into a splenic artery and a hepato-gastroduodenal trunk. The hepato-gastroduodenal trunk presented an unusual course and termination. The right hepatic artery arising from the hepato-gastroduodenal trunk also showed a variant course. Such rare variations are important for gastroenterological surgeons and interventional radiologists due to increase in number of transplantation surgeries and live donor liver transplantations. PMID- 26140228 TI - Erratum: Stable isotope analysis of Joseon people skeletons from the cemeteries of Old Seoul City, the capital of Joseon Dynasty. AB - [This corrects the article on p. 244 in vol. 47, PMID: 25548722.]. PMID- 26140229 TI - Poverty and Awakening Cortisol in Adolescence: The Importance of Timing in Early Life. AB - The deleterious effects of poverty on mental and physical health are routinely argued to operate, at least in part, via dysregulation of the hypothalamus pituitary-adrenal (HPA) axis, although empirical examinations connecting poverty with HPA axis functioning are rare. Research on the effects of timing of poverty is a particularly neglected aspect of this relationship. This study uses 15 years of prospective data from the Study of Early Child Care and Youth Development to assess how exposure to poverty during infancy, childhood, and adolescence is related to awakening cortisol (n = 826), a marker of HPA axis functioning. Among female participants, poverty exposure in infancy and adolescence, but not childhood, was negatively associated with awakening cortisol. Poverty exposure was unrelated to cortisol among male participants. The importance of timing and gender differences are discussed along with directions for future research. PMID- 26140230 TI - Retrieval of functional TCRs from single antigen-specific T cells: Toward individualized TCR-engineered therapies. AB - We have developed a highly versatile platform for the systematic retrieval of T cell receptors (TCRs) from single-antigen-reactive T cells and for characterization of their function and specificity. This approach enables rapid extraction of multiple TCRs from repertoires in individuals and not only broadens the diversity of TCRs suitable for clinical use, but also sets the stage for actively personalized immunotherapeutic strategies. PMID- 26140231 TI - Kick-starting the cancer-immunity cycle by targeting CD40. AB - Stimulation of CD40 on dendritic cells to expand and activate tumor-specific T cells and generate anticancer immunity is an attractive therapeutic approach. Since CD40 agonists exert their effects upstream of checkpoint inhibitors, including PD-1 or PD-L1 antagonists, they are ideal candidates for combination regimens. PMID- 26140233 TI - Splenectomy restores tumoricidal activity to promote elimination of intraocular tumors. AB - We recently demonstrated that splenectomy restores an interaction between CD8+ T cells and macrophages necessary for intraocular tumor elimination. Taking into consideration other studies indicating that intraocular tumor growth does not induce tumor-specific CD8+ T-cell tolerance, our data suggest that splenectomy may influence the phenotype of tumor-associated macrophages. PMID- 26140232 TI - Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen. AB - A key to improving cancer immunotherapy will be the identification of tumor specific "neoantigens" that arise from mutations and augment the resultant host immune response. In this study we identified single nucleotide variants (SNVs) by RNA sequencing of asbestos-induced murine mesothelioma cell lines AB1 and AB1-HA. Using the NetMHCpan 2.8 algorithm, the theoretical binding affinity of predicted peptides arising from high-confidence, exonic, non-synonymous SNVs was determined for the BALB/c strain. The immunoreactivity to 20 candidate mutation-carrying peptides of increased affinity and the corresponding wild-type peptides was determined using interferon-gamma ELISPOT assays and lymphoid organs of non manipulated tumor-bearing mice. A strong endogenous immune response was demonstrated to one of the candidate neoantigens, Uqcrc2; this response was detected in the draining lymph node and spleen. Antigen reactive cells were not detected in non-tumor bearing mice. The magnitude of the response to the Uqcrc2 neoantigen was similar to that of the strong influenza hemagglutinin antigen, a model tumor neoantigen. This work confirms that the approach of RNAseq plus peptide prediction and ELISPOT testing is sufficient to identify natural tumor neoantigens. PMID- 26140234 TI - Depletion of regulatory T cells by targeting CC chemokine receptor type 4 with mogamulizumab. AB - The CC chemokine receptor 4 (CCR4) is highly expressed on type 2 helper T cells and regulatory T (Treg) cells. Mogamulizumab, an anti-CCR4 antibody, reduces the numbers of CCR4+ malignant T cells and CCR4+ Treg cells in cutaneous T-cell lymphoma. Depleting Treg cells by targeting CCR4 has great potential in cancer immunotherapies. PMID- 26140235 TI - Antileukemia T-cell responses in CLL - We don't need no aberration. AB - Effective antigen-specific cancer immunotherapy requires exact knowledge of tumor associated epitopes that can act as rejection antigens. Although the current paradigm views mutation-derived neoantigens as the most promising targets, we have recently demonstrated that leukemia-specific T-cell responses associated with survival benefit in CLL patients target a panel of non-mutated tumor associated antigens. PMID- 26140236 TI - IL-10 enhances CTL-mediated tumor rejection by inhibiting highly suppressive CD4+ T cells and promoting CTL persistence in a murine model of plasmacytoma. AB - Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that regulates immune responses. IL-10 has also been shown to enhance antitumor CD8+ T-cell responses in tumor models although the underlying mechanisms are not fully understood. In this study, we used a series of genetic mouse models and the mouse plasmacytoma J558 model to investigate this issue. J558 tumors grew significantly faster in IL-10-/- mice than in wild type (WT) mice, but similarly in IL-10 -/- Rag2 -/- and Rag2 -/- mice. Tumors from IL-10 -/- mice contained fewer IFN-gamma producing CD8+ and CD4+ T cells than tumors from WT mice. Strikingly, depletion of total CD4+ T cells, but not CD25+ cells, resulted in tumor eradication in IL 10 -/- mice. Adoptive transfer studies revealed that CD4+ T cells from IL-10 -/- mice exhibited more potent suppression of cytotoxic T lymphocyte (CTL)-mediated tumor rejection than their WT counterparts, and IL-10-deficient tumor infiltrating CD4+ T cells expressed higher levels of PD-L1 and CTLA-4 inhibitory molecules. Although IL-10-deficient CD8+ T cells are not defective in activation and initial rejection of tumors, adoptive transfer studies using IL-10-deficient P1CTL transgenic T cells that recognize the tumor rejection antigen P1A reveal that IL-10 is required for long-term persistence of CTLs and control of tumor growth. Thus, we have found that IL-10 enhances antitumor CTL responses by inhibiting highly suppressive CD4+ T cells and promoting CTL persistence. These data have important implications for the design of immunotherapy for human cancer. PMID- 26140237 TI - Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer. AB - Myeloid-derived suppressor cells (MDSCs) play an important role in immune suppression and accumulate under pathologic conditions such as cancer and chronic inflammation. They comprise a heterogeneous population of immature myeloid cells that exert their immunosuppressive function via a variety of mechanisms. Immunoglobulin-like transcript 3 (ILT3) is a receptor containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) that can be expressed on antigen presenting cells and is an important regulator of dendritic cell tolerance. ILT3 exists in a membrane-bound and a soluble form and can interact with a yet unidentified ligand on T cells and thereby induce T-cell anergy, regulatory T cells, or T suppressor cells. In this study, we analyzed freshly isolated peripheral blood mononuclear cells (PBMCs) of 105 patients with non-small cell lung cancer and 20 healthy controls and demonstrated for the first time that ILT3 is expressed on MDSCs. We show that increased levels of circulating MDSCs correlate with reduced survival. On the basis of ILT3 cell surface expression, an ILT3low and ILT3high population of polymorphonuclear (PMN)-MDSCs could be distinguished. Interestingly, in line with the immunosuppressive function of ILT3 on dendritic cells, patients with an increased proportion of PMN-MDSCs and an increased fraction of the ILT3high subset had a shorter median survival than patients with elevated PMN-MDSC and a smaller ILT3high fraction. No correlation between the ILT3high subset and other immune variables was found. ILT3 expressed on MDSCs might reflect a previously unknown mechanism by which this cell population induces immune suppression and could therefore be an attractive target for immune intervention. PMID- 26140239 TI - "In situ" vaccination for systemic effects in follicular lymphoma. AB - Therapeutic vaccines for follicular lymphoma have had limited success. A novel in situ immunotherapeutic strategy combining 3 different treatment modalities induced regression of disseminated follicular lymphoma, which correlated with systemic antitumor T-cell immunity. These results should renew interest in the development of local combined radio- and immunotherapies to achieve abscopal effects. PMID- 26140238 TI - Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation. AB - Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-gamma dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16INK4a and nuclear translocation of p HP1gamma, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo. PMID- 26140240 TI - Local Salmonella immunostimulation recruits vaccine-specific CD8 T cells and increases regression of bladder tumor. AB - The efficacy of antitumoral responses can be increased using combinatorial vaccine strategies. We recently showed that vaccination could be optimized by local administration of diverse molecular or bacterial agents to target and augment antitumoral CD8 T cells in the genital mucosa (GM) and increase regression of cervical cancer in an animal model. Non muscle-invasive bladder cancer is another disease that is easily amenable to local therapies. In contrast to data obtained in the GM, in this study we show that intravesical (IVES) instillation of synthetic toll-like receptor (TLR) agonists only modestly induced recruitment of CD8 T cells to the bladder. However, IVES administration of Ty21a, a live bacterial vaccine against typhoid fever, was much more effective and increased the number of total and vaccine-specific CD8 T cells in the bladder approximately 10 fold. Comparison of chemokines induced in the bladder by either CpG (a TLR-9 agonist) or Ty21a highlighted the preferential increase in complement component 5a, CXCL5, CXCL2, CCL8, and CCL5 by Ty21a, suggesting their involvement in the attraction of T cells to the bladder. IVES treatment with Ty21a after vaccination also significantly increased tumor regression compared to vaccination alone, resulting in 90% survival in an orthotopic murine model of bladder cancer expressing a prototype tumor antigen. Our data demonstrate that combining vaccination with local immunostimulation may be an effective treatment strategy for different types of cancer and also highlight the great potential of the Ty21a vaccine, which is routinely used worldwide, in such combinatorial therapies. PMID- 26140241 TI - Ikaros deficiency in host hematopoietic cells separates GVL from GVHD after experimental allogeneic hematopoietic cell transplantation. AB - The graft-versus-leukemia (GVL) effect following allogeneic hematopoietic stem cell transplantation (allo-HCT) is critical for its curative potential. Hwever, GVL is tightly linked to graft-versus-host disease (GVHD). Among hematological malignancies, acute lymphoblastic leukemia (ALL) is the most resistant to GVL, although the reasons for this remain poorly understood. Clinical studies have identified alterations in Ikaros (Ik) transcription factor as the major marker associated with poor outcomes in ALL. We have shown that the absence of Ik in professional host-derived hematopoietic antigen-presenting cells (APCs) exacerbates GVHD. However, whether Ik expression plays a role in resistance to GVL is not known. In this study we used multiple clinically relevant murine models of allo-HCT to explore whether Ik expression in hematopoietic APCs and/or leukemic cells is critical for increasing resistance to GVL and thus inducing relapse. We found that Ik deficiency in host APCs failed to enhance GVL despite increased GVHD severity. Mechanistic studies with bone marrow (BM) chimeras and tetramer analyses demonstrated reduced tumor-specific immunodominant (gag+) antigen responses in the [B6Ik-/-->B6] group. Loss of GVL was observed when both the leukemia cells and the host APCs were deficient in Ik. We found that calreticulin (CRT) expression in host antigen-presenting dendritic cells (DCs) of Ik-/- animals was significantly lower than in wild-type animals. Rescuing CRT expression in Ik-/- DCs improved leukemic-specific cytotoxic T cell function. Together, our data demonstrate that the absence of Ikaros in host hematopoietic cells promotes resistance to GVL despite increasing GVHD and thus provides a potential mechanism for the poor outcome of Ik-/- ALL patients. PMID- 26140243 TI - Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2 immunotherapy and isotretinoin: a prospective Phase II study. AB - Relapse of high-risk neuroblastoma (HR-NB) is deemed invariably fatal yet increasing numbers of HR-NB patients achieve a second complete/very good partial remission (CR/VGPR), hence the urgency to find a successful consolidative therapy. Identifying efficacy in patients without assessable disease, however, is problematic. We report the first study providing outcome data for this group of patients with poor prognosis. To prevent another relapse, HR-NB patients in second or later CR/VGPR received the anti-GD2 murine antibody 3F8 plus granulocyte-macrophage colony-stimulating factor plus isotretinoin in a Phase II trial. Upon meeting the target aim for progression-free survival (PFS) in the initial cohort of 33 patients, the trial was amended to allow patients who developed human anti-mouse antibody (HAMA) to receive rituximab to ablate HAMA with or without low-dose maintenance chemotherapy until immunotherapy could resume. For the total of 101 study patients, 5-year PFS and overall survival (OS) rates were 33% +/- 5% and 48% +/- 5%, respectively. Among the 33 long-term progression-free survivors, 19 had MYCN amplification, 19 had previously received anti-GD2 immunotherapy plus isotretinoin (as first-line therapy), and 15 never received maintenance chemotherapy. In a multivariate analysis of prognostic factors, only absence of minimal residual disease in bone marrow after 2 cycles of immunotherapy and before initiation of isotretinoin or anti-HAMA therapy was significantly favorable for both PFS and OS. Therefore, long-term PFS is possible for HR-NB patients who achieve at least a second CR/VGPR and receive consolidation that includes anti-GD2 immunotherapy plus isotretinoin, even if the patients received these biological treatments before relapse. Results from this prospective study will aid in the development of future Phase II studies for this growing ultra high-risk patient population. PMID- 26140244 TI - Restoration of natural killer activity in hepatocellular carcinoma by treatment with antibody against granulin-epithelin precursor. AB - Impairment of natural killer (NK) cell activity is an important mechanism of tumor immunoevasion. We have previously shown that expression of granulin epithelin precursor (GEP) in hepatocellular carcinoma (HCC) cells rendered the cells resistant to NK cell immunosurveillance. Here, we examined whether targeting GEP could rescue NK activity in HCC patients. The current study demonstrated that quantities and activities of NK cells were significantly lower in HCC patients compared with healthy individuals, and were negatively correlated with GEP levels in HCC cells. NK cells demonstrated enhanced expression of the stimulatory receptors natural-killer group 2, member D (NKG2D) and CD69, increased secretion of IFN-gamma and perforin, and cytotoxicity against HCC cells upon GEP suppression. Opposite phenotypes of NK cells were observed when GEP was overexpressed in HCC cells. Importantly, GEP blockage by monoclonal antibody A23 restored NK activity in HCC patients and sensitized HCC cells to NK cytotoxicity. Furthermore, A23 induced NK-mediated antibody-dependent cell-mediated cytotoxicity against HCC. In summary, the activity of NK cells in HCC was impaired by GEP expression, which could be rescued by GEP antibody. This study provides new insight for treatments targeting GEP to boost NK activity in HCC patients. PMID- 26140245 TI - Deficient regulatory B cells in human chronic graft-versus-host disease. AB - Human chronic graft-versus-host disease (cGVHD) is a frequent and disabling complication of allogeneic hematopoietic stem cell transplantation. Regulatory B cells (Bregs) are IL-10-producing B cells that are able to inhibit the innate and adaptive immune responses. We have recently demonstrated a defect in regulatory B cells in human cGVHD. PMID- 26140246 TI - The antitumor immune response generated by fractionated radiation therapy may be limited by tumor cell adaptive resistance and can be circumvented by PD-L1 blockade. AB - Fractionated radiation therapy (RT) leads to adaptive changes in the tumor microenvironment that may limit the generation of an antitumor immune response. We demonstrated that fractionated RT led to increased tumor cell expression of programmed cell death ligand 1 (PD-L1) in response to CD8+ T cell production of interferon gamma. Our data reveal that the efficacy of fractionated RT can be significantly improved through the generation of durable systemic immune responses when combined with concurrent, but not sequential, blockade of the PD 1/PD-L1 pathway. PMID- 26140242 TI - Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells. AB - It has become evident that tumor-induced immuno-suppressive factors in the tumor microenvironment play a major role in suppressing normal functions of effector T cells. These factors serve as hurdles that limit the therapeutic potential of cancer immunotherapies. This review focuses on illustrating the molecular mechanisms of immunosuppression in the tumor microenvironment, including evasion of T-cell recognition, interference with T-cell trafficking, metabolism, and functions, induction of resistance to T-cell killing, and apoptosis of T cells. A better understanding of these mechanisms may help in the development of strategies to enhance the effectiveness of cancer immunotherapies. PMID- 26140247 TI - Combined IL-15 and IL-12 drives the generation of CD34+-derived natural killer cells with superior maturation and alloreactivity potential following adoptive transfer. AB - Adoptive transfer of allogeneic natural killer (NK) cells represents a promising treatment approach against cancer, including acute myeloid leukemia (AML). Previously, we reported a cytokine-based culture method for the generation of NK cell products with high cell number and purity. In this system, CD34+ hematopoietic progenitor cells (HPC) were expanded and differentiated into NK cells under stroma-free conditions in the presence of IL-15 and IL-2. We show that combining IL-15 with IL-12 drives the generation of more mature and highly functional NK cells. In particular, replacement of IL-2 by IL-12 enhanced the cytolytic activity and IFNgamma production of HPC-NK cells toward cultured and primary AML cells in vitro, and improved antileukemic responses in NOD/SCID IL2Rgammanull (NSG) mice bearing human AML cells. Phenotypically, IL-12 increased the frequency of HPC-NK cells expressing NKG2A and killer immunoglobulin-like receptor (KIR), which were more responsive to target cell stimulation. In addition, NK15/12 cell products demonstrated superior maturation potential, resulting in >70% positivity for CD16 and/or KIR within 2 weeks after infusion into NSG mice. We predict that higher functionality and faster in vivo maturation will favor HPC-NK cell alloreactivity toward malignant cells in patients, making this cytokine combination an attractive strategy to generate clinical HPC-NK cell products for cancer adoptive immunotherapy. PMID- 26140248 TI - Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8+ T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer. AB - Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8+ lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8+ T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study. PMID- 26140249 TI - Combinatorial immunotherapy with checkpoint blockers solves the problem of metastatic melanoma-An exclamation sign with a question mark. AB - Results from recent clinical trials demonstrate that a combinatorial immunotherapeutic regimen based on 2 distinct checkpoint blockers, namely, the CTLA4-targeting agent ipilimumab and the PD-1-specific molecule nivolumab, causes objective responses in a majority of subjects with advanced melanoma. These findings revolutionize the treatment of a neoplasm that was considered incurable until recently. Nonetheless, announcing the defeat of melanoma appears premature. Indeed, a sizeable fraction of patients does not respond to ipilimumab plus nivolumab, and the long-term efficacy of this immunotherapeutic regimen has not yet been investigated. Moreover, many patients experience severe side effects, calling for the development of strategies that uncouple the efficacy of ipilimumab plus nivolumab from their toxicity. PMID- 26140250 TI - Colorectal cancer: the first neoplasia found to be under immunosurveillance and the last one to respond to immunotherapy? AB - The first study demonstrating that human colorectal carcinoma (CRC) is under robust immunosurveillance was published a decade ago. Today, it is clear that CRC patients with Stage III lesions abundantly infiltrated by effector memory T cells have a better prognosis than subjects with Stage I neoplasms exhibiting no or poor immune infiltration. Thus, immunological parameters have a superior prognostic value for CRC patients than TNM staging or the Dukes classification. In spite of the fact that CRC is the first neoplasia found to be under immunological control, most attempts made so far to cure this malignancy with immunotherapy have failed. With the exception of a minority of lesions characterized by microsatellite instability (MSI), CRC seems to be insensitive to the blockade of immunological checkpoints with monoclonal antibodies (mAbs) specific for cytotoxic T lymphocyte-associated protein 4 (CTLA4), programmed cell death 1 (PDCD1, best known as PD-1) and the PD-1 ligand CD274 (best known as PD L1). Thus, CRC stands in contrast with an increasing number of malignancies that respond to checkpoint blockers. Efforts should therefore be dedicated to the development of strategies to (re)instate immunosurveillance in patients with MSI- CRC, perhaps based on the identification of novel, locally relevant immunological checkpoints. PMID- 26140252 TI - Epstein-Barr virus-induced gene 3-deficiency leads to impaired antitumor T-cell responses and accelerated tumor growth. AB - Epstein-Barr virus-induced gene 3 (EBI3) encoded protein can form heterodimers with IL-27P28, and IL-12P35 to form IL-27, and IL-35. However, IL-27 stimulates, whereas IL-35 inhibits antitumor T-cell responses. IL-27 also limits the Foxp3+ regulatory T cell (Treg) population, whereas IL-35 has been shown to expand Tregs and foster Treg suppressive functions. It remains unclear which group of forces are dominant during antitumor T-cell responses. In this study, we evaluated the tumor growth and antitumor T-cell responses in EBI3-deficient mice that lack both IL-27 and IL-35. We found that injecting B16 melanoma cells into EBI3-deficient C57BL/6 mice, or J558 plasmacytoma cells into EBI3-deficient BALB/c mice resulted in significantly increased tumor growth relative to those implanted in wild-type control mice. Tumors from EBI3-deficient mice contained significantly decreased proportions of CD8+ T cells and increased proportions of CD4+FoxP3+ Treg cells as compared to those from EBI3-intact mice. Tumor-infiltrating T cells from EBI3 deficient mice were impaired in their capacity to produce IFNgamma. Phenotypically, Tregs from EBI3-deficient mice were highly suppressive and produced IL-10 in the tumor microenvironment. Depletion of Tregs or inactivation of the IL-10 pathway significantly abrogated tumor growth enhancement in Ebi3-/- mice. Finally, we showed that Ebi3-/- mice administered a melanoma vaccine failed to mount a CD8+ T-cell response and the vaccine failed to confer tumor rejection in EBI3-deficient mice. Taken together, these results suggest that Ebi3-/- mice show a phenotype of IL-27-deficiency rather than IL-35-deficiency during anti tumor T-cell responses. Thus, our results suggest that endogenous IL-27 is critical for both spontaneous and vaccine-induced antitumor T-cell responses. PMID- 26140251 TI - Cross-talk between tumors can affect responses to therapy. AB - Advanced stages of cancer often involve multiple tumors in different locations in the body. These tumors are associated with a microenvironment that can influence tumor responses to immunotherapy. Whether tumors and their disparate microenvironment can interact together at distance in a multiple tumor setting, through a form of cross-talk, and affect their responses to immunotherapy has never been described. Our study investigated the cross-talk between two tumors with disparate microenvironments in a mouse model. We demonstrated that immunosuppressive visceral tumors could influence distant subcutaneous (SC) tumors to render them resistant to immunotherapy. We observed distinct modifications in the SC tumor microenvironment following cross-talk with kidney tumors that exhibit a type-2 macrophage-related immunosuppressive microenvironment. Indeed, when a concomitant kidney tumor was present in the mouse, the SC tumors were highly infiltrated with M2 macrophages and had a reduced T cell and NK cell effector immune profile. Finally, blocking the M2 associated chemokine CCL2 or depleting macrophages, significantly improved the effect of immunotherapy on growth of SC tumors in the presence of concomitant kidney tumors. This work emphasizes the potential negative influence that a tumor, with a strong immunosuppressive microenvironment, can exert on distant tumors that would normally be treatment-responsive. This report may lead to a new vision of the prioritization in the treatment of advanced metastatic cancer. PMID- 26140254 TI - Corrigendum. AB - [This corrects the article on p. 253 in vol. 5, PMID: 25425503.][This corrects the article on p. 171 in vol. 5, PMID: 25192875.][This corrects the article on p. 315 in vol. 5, PMID: 25167857.][This corrects the article on p. 45 in vol. 6.]. PMID- 26140253 TI - A phenotype from tumor stroma based on the expression of metalloproteases and their inhibitors, associated with prognosis in breast cancer. AB - The objective of the present work was to evaluate the impact of the phenotype of both mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs) in early breast cancer patients, specifically assessed as to their expression of MMP/TIMP relative to their position within the tumor (i.e., localization at the tumor center or invasive front) and the occurrence of distant metastases.. An immunohistochemical study was performed using tissue arrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, 13 and -14, tissue inhibitors of metalloproteinase (TIMP)-1, -2 and -3, both at tumor center and at invasive front, in 107 patients with primary ductal invasive breast tumors. Data were analyzed by unsupervised hierarchical clustering analysis. Our results indicated that MMP-11 expression by MICs, and TIMP-2 expression by CAFs at either the tumor center or the invasive front, were the most potent independent prognostic factors for predicting the clinical outcome of patients. Using the unsupervised hierarchical clustering analysis, we found well defined clusters of cases identifying subgroups of tumors showing a high molecular profile of MMPs/TIMPs expression by stromal cells (CAFs and MICs), both at the tumor center and at the invasive front, which were strongly associated with a higher prevalence of distant metastasis. In addition, we found combinations of these clusters defining subpopulations of breast carcinomas differing widely in their clinical outcome. The results presented here identify biologic markers useful to categorize patients into different subgroups based on their tumor stroma, which may contribute to improved understanding of the prognosis of breast cancer patients. PMID- 26140255 TI - Demographic, dietary and physical activity predictors of general and abdominal obesity among university students: a cross-sectional study. AB - BACKGROUND: Obesity has become a disease of global public health concern in both developing and developed countries. We investigated the influence of socio demographic, dietary habits and physical activity levels on general and abdominal obesity among a sample of university students in Ghana. METHODS: This cross sectional study was carried out among a sample of 552 students attending the University for Development Studies, School of Medicine and Health Sciences, Tamale, Ghana. Demographic characteristics were assessed using questionnaire. Dietary habits were measured by means of food frequency questionnaires. Anthropometric measurements were done using appropriate methods. Physical activity levels were measured using the World Health Organization (WHO) global physical activity questionnaire. Spearman's nonparametric correlation coefficient and multinomial logistic regression analysis were used to investigate the determinants of general and abdominal obesity. RESULTS: The prevalence of general overweight/obesity (25.8 % vs. 5.9 %) and abdominal obesity (40.9 % vs. 0.8 %) was higher in female students than in male students. General overweight/obesity was less likely in students who engaged in vigorous physical activity (Adjusted Odds Ratio (AOR) = 0.3, 95 % CI = 0.1 - 0.7, p = 0.004), but more likely in students who consumed fruits and vegetables > 3 days per week (AOR = 2.6, 95 % CI = 1.2 - 5.4, p = 0.015). Abdominal obesity was also less likely in male students (AOR = 0.0, 95 % CI = 0.0 - 0.5, p = 0.017) but more likely in students who consumed roots and tubers > 3 times per week (AOR = 8.0, 95 % CI = 2.2 - 10.1, p = 0.017) and in those who consumed alcoholic and non-alcoholic beverages > 3 times per week (AOR = 8.2, 95 % CI = 2.2 - 31.1, p = 0.002). CONCLUSION: Demographic factors, dietary habits and physical activity levels were found to be associated to general overweight/obesity and abdominal obesity. General overweight/obesity was associated to the consumption of fruits and vegetables > 3 times a week. The consumption of roots and tubers > 3 times per week and alcoholic and non-alcohol beverages > 3 times a week was associated to abdominal obesity. Engagement in vigorous physical activity and being male were negatively associated to general overweight/obesity and abdominal obesity respectively. Promotion of active lifestyles in young adults should be encouraged. PMID- 26140256 TI - Microscale spatial distributions of microbes and viruses in intertidal photosynthetic microbial mats. AB - Intertidal photosynthetic microbial mats from the Wadden Sea island Schiermonnikoog were examined for microscale (millimetre) spatial distributions of viruses, prokaryotes and oxygenic photoautotrophs (filamentous cyanobacteria and benthic diatoms) at different times of the year. Abundances of viruses and prokaryotes were among the highest found in benthic systems (0.05-5.43 * 10(10) viruses g(-1) and 0.05-2.14 * 10(10) prokaryotes g(-1)). The spatial distribution of viruses, prokaryotes and oxygenic photoautotrophs were highly heterogeneous at mm scales. The vertical distributions of both prokaryotic and viral abundances were related to the depth of the oxygenic photoautotrophic layer, implying that the photosynthetic mat fuelled the microbial processes in the underlying layer. Our data suggest that viruses could make an important component in these productive environments potentially affecting the biodiversity and nutrient cycling within the mat. PMID- 26140257 TI - Clinical picture: multiple sites of ectopic pancreatic tissue. AB - A case is presented with multiple sites of ectopic pancreatic tissue in the gastro-intestinal tract. The sites were found in the stomach and duodenum, one site of ectopic pancreatic tissue presented with necrotizing pancreatitis. Ectopic pancreatic tissue can be defined as all pancreatic tissue, with no anatomical or vascular continuity with the orthotopic pancreas. The ectopic tissue most likely originates from the spreading of cells, during the allocation of structures derived from the foregut in the embryonic phase. Over ninety percent of ectopic tissue presents in the upper gastrointestinal tract, although other locations have been described. To date this is the first case-report about a patient with multiple localizations of ectopic pancreatic tissue. PMID- 26140258 TI - Inhibition of emotion-related autonomic arousal by skin pressure. AB - BACKGROUND: Negative emotions can cause discomforting autonomic arousal, which can be difficult to inhibit using willpower alone. Although previous physiological studies have reported that skin pressure at certain bilateral locations reflexively inhibits sympathetic nervous system activity, few studies have tested the effect of this inhibition on emotion-related autonomic arousal in humans. FINDINGS: I recorded skin potential response (SPR) and heart rate (HR) in healthy participants in response to loud noises presented concomitantly with or without skin pressure applied bilaterally to the sides of the chest. Weaker SPR and lower HR were observed in response to the noises accompanied by skin pressure. CONCLUSIONS: These findings indicate that skin pressure can be an easy and effective method to inhibit autonomic arousal related to negative emotions. PMID- 26140259 TI - Regulation of the microvascular circulation in the leg muscles, pancreas and small intestine in rats. AB - To study the microvascular circulation, we examined the proportion of open and functioning capillaries in the leg muscles, pancreas and small intestine of anesthetized rats. Fluorescein isothiocyanate (FITC)-labeled Lycopersicon esculentum lectin was injected into the heart and allowed to circulate for 3 min to label open and functioning capillaries. Specimens were removed, frozen, sectioned and double-immunostained. Using one section, open and functioning capillaries were detected by immunostaining for this lectin bound to endothelial cells, while all capillaries were visualized by immunostaining for platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31). These capillaries were semi-automatically detected and counted by fluorescence microscopy. The percentages of open and functioning capillaries were as follows: the soleus muscle, 93.0 +/- 5.5%; superficial zone of the gastrocnemius muscle, 90.8 +/- 6.2%; deep zone of the gastrocnemius muscle, 95.6 +/- 4.0%; the plantaris muscle, 94.1 +/- 2.7%; the pancreas, 86.3 +/- 11.7%; and the small intestine, 91.1 +/- 4.9% (n = 8, each). There was no significant difference among these data by the Kruskal-Wallis test. This study clearly demonstrated that the proportions of open and functioning capillaries are high and similar among the leg muscles, pancreas and small intestine in spite of their structural and functional differences. This finding agrees with previous studies and supports the notion that the microvascular circulation is mainly controlled by changing of the blood flow in each capillary rather than changing the proportion of open and functioning capillaries. PMID- 26140260 TI - Genetic variation for induced and basal resistance against leaf pathogen Pseudomonas syringae pv. tomato DC3000 among Arabidopsis thaliana accessions. AB - In Arabidopsis thaliana, significant efforts to determine the effect of naturally occurring variation between phenotypically divergent accessions on different biotic or abiotic stresses are underway. Although it is usually assumed that induced systemic resistance (ISR) against pathogen will covary with plant genetic variation, this assumption has not been tested rigorously in previous experiments. Here, we investigated heritable variation in resistance as well as Penicillium simplicissimum GP17-2-mediated ISR to the bacteria Pseudomonas syringae pv. tomato DC3000 (Pst) among a worldwide collection of accessions of A. thaliana. In this study, 75 Arabidopsis accessions were screened against the bacteria Pst following induction and non-induction treatment and their resistance levels were determined by measuring three components of A. thaliana resistance (infected leaf number, disease severity and pathogen growth). We observed extensive quantitative variation in the number of infected leaves, severity of disease symptoms and the bacterial population size among 75 accessions of A. thaliana infected with Pst. On the contrary, about a two-third of the accessions (49 accessions) showed a reduction in infected leaf number, disease severity and pathogen proliferation after treatment with GP17-2, indicating that GP17-2 induction of resistance is ecotype specific in Arabidopsis. The level of suppression was more pronounced for percent disease severity and pathogen proliferation than for number of infected leaves in ISR-inducible accessions. Accessions non-responsive to GP17-2 treatment generally appeared to be associated with higher basal resistance to infection by Pst. Future study with these parental lines employing a variety of crossing schemes may facilitate identification of major trait loci responsible for GP17-2-mediated ISR in Arabidopsis. PMID- 26140261 TI - Krasnoselskii-type algorithm for zeros of strongly monotone Lipschitz maps in classical banach spaces. AB - Let [Formula: see text], [Formula: see text], and [Formula: see text] be a strongly monotone and Lipschitz mapping. A Krasnoselskii-type sequence is constructed and proved to converge strongly to the unique solution of [Formula: see text]. Furthermore, our technique of proo f is of independent interest. PMID- 26140262 TI - Operative technique and early experience for robotic-assisted laparoscopic nephroureterectomy (RALNU) using da Vinci Xi. AB - PURPOSE: Robotic-assisted laparoscopic nephroureterectomy (RALNU) has been previously utilized for management of upper tract urothelial carcinoma. The da Vinci Xi surgical system was released in April of 2014. We describe our operative technique and early experience for RALNU using the da Vinci Xi system highlighting unique features of this surgical platform. MATERIALS AND METHODS: A total of 10 patients with a diagnosis of upper tract urothelial carcinoma underwent RALNU using the da Vinci Xi system between April and November of 2014. A novel, oblique "in line" robotic trocar configuration was utilized to access the upper abdomen (nephrectomy portion) and pelvis (bladder cuff excision) without undocking. The port hopping feature of da Vinci Xi was utilized to facilitate optimal, multi-quadrant visualization during RALNU. RESULTS: Robotic assisted laparoscopic nephroureterectomy was successfully completed without open conversion in all 10 patients. Mean operative time was 184 min (range 140-300 min), mean estimated blood loss was 121 cc (range 60-300 cc), and mean hospital stay was 2.4 days. Final pathology demonstrated high grade urothelial carcinoma in all patients. Surgical margins were negative in all patients. No intra operative complications were encountered. One patient developed a pulmonary embolus after being discharged. No patients required a blood transfusion. Mean patient follow-up was 130 days (range 15-210 days). CONCLUSION: The use of da Vinci Xi with a novel, oblique "in line" port configuration and camera port hopping technique allows for an efficient and reproducible method for RALNU without the need for repositioning the patient or the robot during surgery. PMID- 26140263 TI - Effects of elevated root zone CO2 on xerophytic shrubs in re-vegetated sandy dunes at smaller spatial and temporal scales. AB - The below-ground CO2 concentration in some crusted soils or flooded fields is usually ten or hundred times larger than the normal levels. Recently, a large number of studies have focused on elevated CO2 in the atmosphere; however, only few have examined the influence of elevated root zone CO2 on plant growth and vegetation succession. In the present study, a closed-air CO2 enrichment (CACE) system was designed to simulate elevated CO2 concentrations in the root zones. The physio-ecological characteristics of two typical xerophytic shrubs C. korshinskii and A. ordosica in re-vegetated desert areas were investigated at different soil CO2 concentrations from March 2011 to October 2013. Results showed that plant growth, phenophase, photosynthetic rate, stomatal conductance, transpiration rate, and water use efficiency for the two xerophytic shrubs were all increased at first and then decreased with increasing soil CO2 concentrations, and the optimal soil CO2 concentration thresholds for C. korshinskii and A. ordosica were 0.554 and 0.317%, respectively. And A. ordosica was more tolerate to root zone CO2 variation when compared with C. korshinskii, possible reasons and vegetation succession were also discussed. PMID- 26140264 TI - Genomics of the honey bee microbiome. AB - The guts of honey bee workers contain a distinctive community of bacterial species. They are microaerophilic or anaerobic, and were not clearly deliniated by earlier studies relying on laboratory culture of isolates under atmospheric oxygen levels. Recently, a more complete picture of the potential metabolism and functions of these bacteria has been possible, using genomic approaches based on metagenomic samples, as well as cultured isolates. Of these, most are host restricted and are generally absent outside adult guts. These species include both Gram negative groups, such as Gilliamella apicola and Snodgrassella alvi, and Gram positive groups such as certain Lactobacillus and Bifidobacterium species. These gut bacterial species appear to have undergone long term coevolution with honey bee and, in some cases, bumble bee hosts. Prediction of gene functions from genome sequences suggests roles in nutrition, digestion, and potentially in defense against pathogens. In particular, genes for sugar utilization and carbohydrate breakdown are enriched in G. apicola and the Lactobacillus species. PMID- 26140265 TI - A comparative analysis of reproductive biology of insect vectors of human disease. AB - Studying the reproductive strategies of insect species that transmit diseases to humans can identify new exploitable targets for the development of vector control methods. Here we describe shared characteristics and individual features of the reproductive biology of three major disease vectors: Anopheles gambiae, Aedes aegypti and Glossina morsitans. Current studies are identifying i) species specific molecular cascades that determine female monandrous behavior, ii) core aspects of egg development that could be disrupted for controlling natural populations, and iii) the increasingly apparent role of resident microbiota in shaping reproductive success and disease transmission potential. The recent completion of multiple genome sequencing projects is allowing comparative genomics studies that not only increase our knowledge of reproductive processes but also facilitate the identification of novel targets for vector control. PMID- 26140266 TI - Ability of community-based prostate cancer screening to target an appropriate and underserved population. AB - Screening is not universally beneficial due to over- and under-diagnosis, and false positives that beget additional testing and associated adverse events and expense. We examined data from all men who participated in a mass community prostate cancer screening between May 2009 and September 2010. The data contained information regarding patient demographics, family history of prostate cancer, lower urinary tract symptoms, prior history of prostate cancer, most recent digital rectal examination, and the presence of an established relationship with a physician. Current American Urological Association screening recommendations were then applied to determine the appropriateness of our outreach effort. A total of 438 men (mean age 66.5 years) underwent screening. A total of 106 (24.2%) patients in our study met contemporary criteria for screening. Of these men, the vast majority was well educated, well insured, and well informed about the need for prostate cancer screening. Based on these data, mass community-based prostate cancer screening does not appear to identify and screen at-risk men. Future efforts at mass screening should more carefully target men most likely to benefit. PMID- 26140267 TI - Recurrent urinary tract infections in children: Preventive interventions other than prophylactic antibiotics. AB - Urinary tract infection (UTI) is one of the most common childhood infections. Permanent renal cortical scarring may occur in affected children, especially with recurrent UTIs, leading to long-term complications such as hypertension and chronic renal failure. To prevent such damage, several interventions to prevent UTI recurrences have been tried. The most established and accepted prevention at present is low dose long-term antibiotic prophylaxis. However it has a risk of break through infections, adverse drug reactions and also the risk of developing antibiotic resistance. The search is therefore on-going to find a safer, effective and acceptable alternative. A recent meta-analysis did not support routine circumcision for normal boys with no risk factors. Vaccinium Macrocarpon (cranberry), commonly used against UTI in adult women, is also effective in reducing the number of recurrences and related antimicrobial use in children. Sodium pentosanpolysulfate, which prevents bacterial adherence to the uroepithelial cells in animal models, has shown conflicting results in human trials. When combined with antibiotic, Lactobacillus acidophilus (LA-5) and Bifidobacterium, by blocking the in vitro attachment of uropathogenic bacteria to uroepithelial cells, significantly reduce in the incidence of febrile UTIs. Deliberate colonization of the human urinary tract of patients with recurrent UTI with Escherichia-coli (E. coli) 83972 has resulted in subjective benefit and less UTI requiring treatment. The non-pathogenic E. coli isolate NU14 DeltawaaL is a candidate to develop live-attenuated vaccine for the treatment and prevention of acute and recurrent UTI. Diagnosing and treating dysfunctional elimination syndromes decrease the incidence of recurrent UTI. A meta-analysis found the lack of robust prospective randomized controlled trials limited the strength of the established guidelines for surgical management of vesicoureteral reflux. In conclusion, several interventions, other than antibiotic prophylaxis, for the prevention of recurrent UTI have been tried and, although showing some promise, they do not provide so far a definitive effective answer. Finding suitable alternatives still requires further high quality research of those seemingly promising interventions. PMID- 26140268 TI - Costimulatory blockade: A novel approach to the treatment of glomerular disease? AB - Costimulatory pathways (Cluster of differentiation 28, tumor necrosis factor related, adhesion and T Cell Ig- and mucin-domain molecules) regulating the interactions between receptors on the T cells and their ligands expressed on several cell types, have a key role in controlling many immunological and non immunological processes. Indeed, accumulating evidence indicate that these molecules are involved in the pathogenesis of numerous conditions, such as allograft rejection, atherosclerosis, rheumatoid arthritis, psoriasis and renal diseases, including glomerulonephritis. Primary or secondary (i.e., associated with infections, drugs or systemic diseases, such as systemic lupus erythematosus, diabetes, etc.) glomerulonephritis represent a group of heterogeneous diseases with different pathogenic mechanisms. Since costimulatory molecules, in particular CD80 and CD40, have been found to be expressed on podocytes in the course of different experimental and clinical glomerulonephritis, costimulation has been thought as a new therapeutic target for patients with glomerular diseases. However, although experimental data suggested that the blockade of costimulatory pathways is effective and safe in the prevention and treatment of glomerular diseases, clinical trials reported contrasting results. So, at this moment, there is not a strong evidence for the general use of costimulatory blockade as an alternative treatment strategy in patients with primary or secondary glomerulonephritis. Here, we critically discuss the current data and the main issues regarding the development of this innovative therapeutic approach. PMID- 26140269 TI - Clinical neurological examination vs electrophysiological studies: Reflections from experiences in occupational medicine. AB - Seventy-five percent of upper limb disorders that are related to work are regarded as diagnostically unclassifiable and therefore challenging to the clinician. Therefore it has been generally less successfully to prevent and treat these common and frequently disabling disorders. To reach a diagnosis requires the identification of the responsible pathology and the involved tissues and structures. Consequently, improved diagnostic approaches are needed. This editorial discusses the potentials of using the clinical neurologic examination in patients with upper limb complaints related to work. It is argued that a simple but systematic physical approach permits the examiner to frequently identify patterns of neurological findings that suggest nerve afflictions and their locations, and that electrophysiological studies are less likely to identify pathology. A diagnostic algorithm for the physical assessment is provided to assist the clinician. Failure to include representative neurological items in the physical examination may result in patients being misinterpreted, misdiagnosed and mistreated. PMID- 26140271 TI - Exercise for tendinopathy. AB - Tendinopathies are one of the most common sports/musculoskeletal injury in modern western societies. Many physiotherapy approaches have been recommended in the literature for the management of tendinopathy. The most effective treatment in the management of tendinopathy is the eccentric training. Load, speed and frequency of contractions are the three principles of eccentric exercises, discussed in this report. However, eccentric training is not effective for all patients with tendinopathy and the effectiveness of this approach when applied as monotherapy is lower than it is applied as part of the rehabilitation process. For this reason, clinicians combine eccentric training with other physiotherapy techniques such as stretching, isometric and lumbar stability exercises, electrotherapy, manual therapy, soft tissue manipulation techniques, taping and acupuncture in the management of tendinopathies. Further research is needed to find out which treatment strategy combined with eccentric training will provide the best results in the rehabilitation of tendinopathy. PMID- 26140272 TI - Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations. AB - Bartter and Gitelman syndromes (BS and GS) are inherited disorders resulting in defects in renal tubular handling of sodium, potassium and chloride. Previously considered as genotypic and phenotypic heterogeneous diseases, recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition. Although they share some characteristic metabolic abnormalities such as hypokalemia, metabolic alkalosis, hyperplasia of the juxtaglomerular apparatus with hyperreninemia, hyperaldosteronism, the clinical and laboratory manifestations may not always allow distinction between them. Diuretics tests, measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change (< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS, except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists. The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children. Clinical symptoms and biochemical markers of GS and classic form of BS (type III) may overlap and thus genetic analysis may specify the real cause of symptoms. However, although genetic analysis is available, its use remains limited because of limited availability, large gene dimensions, lack of hot-spot mutations, heavy workup time and costs involved. Furthermore, considerable overlap exists between the different genotypes and phenotypes. Although BS and GS usually have distinct presentations and are associated with specific gene mutations, there remains considerable overlap between their phenotypes and genotypes. Thus, they are better described as a spectrum of clinical manifestations caused by different gene mutations. PMID- 26140270 TI - Cross-reactivity between aeroallergens and food allergens. AB - In patients with respiratory allergy, cross-reactivity between aeroallergens and foods may induce food allergy, symptoms ranging from oral allergy syndrome to severe anaphylaxis. Clinical entities due to IgE sensitization to cross-reactive aeroallergen and food allergen components are described for many sources of plant origin (pollen-food syndromes and associations, such as birch-apple, cypress peach and celery-mugwort-spice syndromes, and mugwort-peach, mugwort-chamomile, mugwort-mustard, ragweed-melon-banana, goosefoot-melon associations), fungal origin (Alternaria-spinach syndrome), and invertebrate, mammalian or avian origin (mite-shrimp, cat-pork, and bird-egg syndromes). Clinical cases of allergic reactions to ingestion of food products containing pollen grains of specific plants, in patients with respiratory allergy to Asteraceae pollen, especially mugwort and ragweed, are also mentioned, for honey, royal jelly and bee polen dietary supplements, along with allergic reactions to foods contaminated with mites or fungi in patients with respiratory allergy to these aeroallergens. Medical history and diagnosis approach may be guided by the knowledge about the diverse cross-reacting allergens involved, and by the understanding of these clinical entities which may vary significantly or may be overlapping. The association between primary IgE sensitization with respiratory symptoms to inhaled allergens and food allergy due to cross-reactive allergen components is important to assess in allergy practice. The use of molecular-based diagnosis improves the understanding of clinically relevant IgE sensitization to cross reactive allergen components from aeroallergen sources and foods. PMID- 26140273 TI - Neurally adjusted ventilator assist in very low birth weight infants: Current status. AB - Continuous improvements in perinatal care have resulted in increased survival of premature infants. Their immature lungs are prone to injury with mechanical ventilation and this may develop into chronic lung disease (CLD) or bronchopulmonary dysplasia. Strategies to minimize the risk of lung injury have been developed and include improved antenatal management (education, regionalization, steroids, and antibiotics), exogenous surfactant administration and reduction of barotrauma by using exclusive or early noninvasive ventilatory support. The most frequently used mode of assisted ventilation is pressure support ventilation that may lead to patient-ventilator asynchrony that is associated with poor outcome. Ventilator-induced diaphragmatic dysfunction or disuse atrophy of diaphragm fibers may also occur. This has led to the development of new ventilation modes including neurally adjusted ventilatory assist (NAVA). This ventilation mode is controlled by electrodes embedded within a nasogastric catheter which detect the electrical diaphragmatic activity (Edi) and transmit it to trigger the ventilator in synchrony with the patient's own respiratory efforts. This permits the patient to control peak inspiratory pressure, mean airway pressure and tidal volume. Back up pressure control (PC) is provided when there is no Edi signal and no pneumatic trigger. Compared with standard conventional ventilation, NAVA improves blood gas regulation with lower peak inspiratory pressure and oxygen requirements in preterm infants. NAVA is safe mode of ventilation. The majority of studies have shown no significant adverse events in neonates ventilated with NAVA nor a difference in the rate of intraventricular hemorrhage, pneumothorax, or necrotizing enterocolitis when compared to conventional ventilation. Future large size randomized controlled trials should be established to compare NAVA with volume targeted and pressure controlled ventilation in newborns with mature respiratory drive. Most previous studies and trials were not sufficiently large and did not include long-term patient oriented outcomes. Multicenter, randomized, outcome trials are needed to determine whether NAVA is effective in avoiding intubation, facilitating extubation, decreasing time of ventilation, reducing the incidence of CLD, decreasing length of stay, and improving long-term outcomes such as the duration of ventilation, length of hospital stay, rate of pneumothorax, CLD and other major complications of prematurity. In order to prevent barotrauma, next generations of NAVA equipment for neonatal use should enable automatic setting of ventilator parameters in the backup PC mode based on the values generated by NAVA. They should also include an upper limit to the inspiratory time as in conventional ventilation. The manufacturers of Edi catheters should produce smaller sizes available for extreme low birth weight infants. Newly developed ventilators should also include leak compensation and high frequency ventilation. A peripheral flow sensor is also essential to the proper delivery of all modes of conventional ventilation as well as NAVA. PMID- 26140275 TI - Past, present and future of cyanide antagonism research: From the early remedies to the current therapies. AB - This paper reviews milestones in antidotal therapies for cyanide (CN) spanning early remedies, current antidotal systems and research towards next generation therapies. CN has been a part of plant defense mechanisms for millions of years. It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent. The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929. These fundamental studies led to a variety of antidotes, including indirect CN binders that generate methemoglobin, direct CN binders such as hydroxocobalamin, and sulfur donors that convert CN to the less toxic thiocyanate. Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide (NO) in the body. The discovery of NO's ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites. Presently used CN therapies include: methemoglobin/NO generators (e.g., sodium nitrite, amyl nitrite, and dimethyl aminophenol), sulfur donors (e.g., sodium thiosulfate and glutathione), and direct binding agents [(e.g., hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid (dicobalt edetate)]. A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios. New antidotes, formulations, and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures. PMID- 26140276 TI - Current Helicobacter pylori treatment in 2014. AB - Helicobacter pylori is one of the most commonly seen bacterium worldwide. It's in the etiology of multiple gastrointestinal diseases, ranging from gastritis to gastric carcinoma. The antimicrobial therapies, which are frequently prescribed empirically, are losing their effectivity as a result of the increasing antimicrobial resistance. As the standard triple therapy is now left especially in areas with high-clarithromycin resistance due to decreased eradication rates, quadruple therapies are recommended in most regions of the world. Alternatively, concomitant, sequential and hybrid therapies are used. There is still a debate going on about the use of levofloxacin-based therapy in order to prevent the increase in quinolone resistance. If no regimen can achieve the desired eradication rate, culture-guided individualized therapies are highly recommended. Probiotics, statins and n-acetylcysteine are helpful as adjuvant therapies in order to increase the effectiveness of the eradication therapy. Herein, we focused on different eradication regimens in order to highlight the current Helicobacter pylori treatment. PMID- 26140277 TI - Genetic structure and population diversity of eleven edible herbs of Eastern Crete. AB - BACKGROUND: The present work aimed to investigate the genetic structure of 11 edible herbs grown in the wild of eastern Crete that are becoming vulnerable due to habitat destruction and unregulated harvesting. Thirty three populations (268 individuals) of Reichardia picroides, Scolymus hispanicus, Scandix pecten veneris, Leontodon tuberosus, Cichorium spinosum, Sonchus asper ssp. glaucescens, Urospermum picroides, Prasium majus, Hypochoeris radicata, Centaurea raphanina ssp. raphanina and Anagallis arvensis were collected and identified from nine regions with distinct microclimate (Lassithi prefecture), and their genetic composition was studied by means of RAPD markers. RESULTS: A total of ten primers per population were used to detect genetic diversity and bootstrap analysis was conducted for clustering the samples. High levels of heterogeneity were revealed while the Analysis of Molecular Variance documented that variance was allocated mainly within populations and at a lesser extent among populations. Fst values among regions were moderate to high, suggesting partial population fragmentation. Bayesian structure analysis revealed fine genetic composition and substantial admixture between species present in different regions, although clustering was mainly geographically related. CONCLUSIONS: High altitude regions, with little residential and agricultural development (Kefala, Agrilos, Ziros and Tziritis), were the areas where high biodiversity was detected. On the other hand, coastal regions had lower biodiversity, probably due to degradation of their habitat. PMID- 26140274 TI - Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms. AB - Although myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) are considered to be synonymous, the definitional criteria for ME and CFS define two distinct, partially overlapping, clinical entities. ME, whether defined by the original criteria or by the recently proposed criteria, is not equivalent to CFS, let alone a severe variant of incapacitating chronic fatigue. Distinctive features of ME are: muscle weakness and easy muscle fatigability, cognitive impairment, circulatory deficits, a marked variability of the symptoms in presence and severity, but above all, post-exertional "malaise": a (delayed) prolonged aggravation of symptoms after a minor exertion. In contrast, CFS is primarily defined by (unexplained) chronic fatigue, which should be accompanied by four out of a list of 8 symptoms, e.g., headaches. Due to the subjective nature of several symptoms of ME and CFS, researchers and clinicians have questioned the physiological origin of these symptoms and qualified ME and CFS as functional somatic syndromes. However, various characteristic symptoms, e.g., post-exertional "malaise" and muscle weakness, can be assessed objectively using well-accepted methods, e.g., cardiopulmonary exercise tests and cognitive tests. The objective measures acquired by these methods should be used to accurately diagnose patients, to evaluate the severity and impact of the illness objectively and to assess the positive and negative effects of proposed therapies impartially. PMID- 26140278 TI - PI3King the right partner: unique interactions and signaling by p110beta. AB - Phosphoinositide 3-kinases (PI3Ks) are central regulators of cellular responses to extracellular stimuli, and are involved in growth, proliferation, migration, and metabolism. The Class I PI3Ks are activated by Receptor Tyrosine Kinases (RTKs) or G Protein-Coupled Receptors (GPCRs), and their signaling is commonly deregulated in disease conditions. Among the class I PI3Ks, the p110beta isoform is unique in being activated by both RTKs and GPCRs, and its ability to bind Rho GTPases and Rab5. Recent studies have characterized these p110beta interacting partners, defining the binding mechanisms and regulation, and thus provide insight into the function of this kinase in physiology and disease. This review summarizes the developments in p110beta research, focusing on the interacting partners and their role in p110beta-mediated signaling. PMID- 26140279 TI - Oral contraceptives combined with interferon beta in multiple sclerosis. AB - OBJECTIVE: To test the effect of oral contraceptives (OCs) in combination with interferon beta (IFN-beta) on disease activity in patients with relapsing remitting multiple sclerosis (RRMS). METHODS: One hundred fifty women with RRMS were randomized in a 1:1:1 ratio to receive IFN-beta-1a subcutaneously (SC) only (group 1), IFN-beta-1a SC plus ethinylstradiol 20 MUg and desogestrel 150 MUg (group 2), or IFN-beta-1a SC plus ethinylestradiol 40 MUg and desogestrel 125 MUg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures. RESULTS: The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval [CI] 0.81-1.14) in group 1, 0.84 (95% CI 0.66-1.02) in group 2, and 0.72 (95% CI 0.53-0.91) in group 3, with a decrease of 14.1% (p = 0.24) and 26.5% (p = 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadolinium-enhancing lesions was greater in group 3 than in group 1 (p = 0.03). No significant differences were detected in other secondary endpoints. IFN-beta or OC discontinuations were equally distributed across groups. CONCLUSIONS: Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in women with RRMS, IFN-beta plus ethinylstradiol and desogestrel decreases the cumulative number of active brain MRI lesions compared with IFN-beta alone. PMID- 26140280 TI - Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO. AB - OBJECTIVE: To assess the clinical relevance of the differential binding of antibodies against the 2 main aquaporin-4 (AQP4) isoforms in neuromyelitis optica (NMO) patient sera using stably transfected human embryonic kidney cells. METHODS: Flow cytometry of human embryonic kidney cells stably transfected with either M23 or M1 AQP4 was used to measure antibody endpoint titers in 52 remission samples and 26 relapse samples from 34 patients with clinically well characterized AQP4 antibody-positive NMO/NMO spectrum disorder. RESULTS: The AQP4 M23 (40-61,440) and AQP4 M1 (<20-20,480) titers varied widely between patients, as did the M23:M1 antibody ratio (1-192). In 76 of 78 samples, binding to M23 was higher than binding to M1, including during relapses and remissions (p < 0.0001), and the M23:M1 ratio was relatively constant within an individual patient. Titers usually fell after immunosuppression, but the titers at which relapses occurred varied markedly; no threshold level for relapses could be identified, and relapses could occur without a rise in titers. Relapse severity did not correlate with M23 or M1 antibody titers, although there was a correlation between the earliest M23 titers and annualized relapse rates. The M23:M1 ratio and absolute M23 and M1 titers did not relate to age at disease onset, ethnicity, disease severity, phenotype, or relapses at different anatomical sites. CONCLUSION: Relative AQP4 antibody binding to M23 and M1 isoforms differs between patients but there is no consistent association between these differences and clinical characteristics of disease. Nevertheless, the M23 isoform provided a slightly more sensitive substrate for AQP4-antibody assays, particularly for follow-up studies. PMID- 26140281 TI - Hematologic modifications in natalizumab-treated multiple sclerosis patients: An 18-month longitudinal study. AB - OBJECTIVE: To monitor the hematologic modifications in the peripheral blood of patients with relapsing-remitting multiple sclerosis treated with natalizumab. METHODS: The cohort included 44 patients with relapsing-remitting multiple sclerosis treated monthly with natalizumab for 18 months. Peripheral blood was collected before treatment initiation and on a monthly basis during the treatment course. Complete blood cell count was performed using automated hematology systems. Blood smears were prepared and analyzed when abnormal values were detected. RESULTS: Mean total white blood cell, lymphocyte, and eosinophil counts were significantly higher 1 month after treatment initiation and remained stable during the 18 months of follow-up. Monocyte counts increased progressively during the 18-month treatment with natalizumab. Erythroblasts and neutrophil precursors were absent before treatment initiation but were present in 16% and 6.8% of patients, respectively, 1 month after the first natalizumab infusion. The proportion of patients with erythroblasts and neutrophil precursors remained stable throughout the 18-month follow-up period. On an individual patient basis, a fluctuating level of erythroblasts and neutrophil precursors was observed. No difference in mean erythrocyte, hemoglobin, hematocrit, thrombocyte, and neutrophil levels was observed before and after 18 months of natalizumab treatment. No cases of myelodysplastic syndrome or acute leukemia were observed. CONCLUSION: Chronic treatment with natalizumab is associated with significant modifications in complete blood cell count, including emergence of hematopoietic precursors that are not present in peripheral blood under normal conditions. None of these modifications were associated with malignancy. PMID- 26140282 TI - Transient anti-NMDAR encephalitis in a newborn infant due to transplacental transmission. PMID- 26140283 TI - Erratum: Encephalomyeloneuropathy with CRMP-5 antibodies in a patient with a primary mediastinal serinoma. AB - [This corrects the article on p. e82 in vol. 2, PMID: 25798447.]. PMID- 26140284 TI - THE QUICK DEMENTIA RATING SYSTEM (QDRS): A RAPID DEMENTIA STAGING TOOL. AB - INTRODUCTION: Test the validity and reliability of the Quick Dementia Rating System (QDRS), a rapid dementia staging tool. METHODS: The QDRS was tested in 267 patient-caregiver dyads compared with Clinical Dementia Ratings (CDR), neuropsychological testing, and gold standard measures of function, mood, and behavior. Psychometric properties including, item variability, floor and ceiling effects, concurrent and construct validity, and internal consistency were determined. The QDRS was used to derive an independent CDR and sum of boxes. Interscale reliability between QDRS and CDR was tested using intraclass correlation coefficients (ICC). Area under the receiver operator characteristic curves (AUC) tested discrimination properties of QDRS across CDR stages. RESULTS: QDRS scores increased with higher CDR staging and poorer neuropsychological performance (p's <.001). The QDRS demonstrated low floor and ceiling effects; excellent known-groups validity across CDR stages (p's<.001); construct validity against cognitive, behavioral, and functional measures (p-value's:0.004 to <0.001); and reliability (Cronbach alpha: 0.86-0.93). The QDRS demonstrated differential scores across different dementia etiologies. The AUC for the QDRS was 0.911 (95%CI 0.86-0.96) and for the CDR-SB was 0.996 (95% CI: 0.99-1.0) demonstrating comparable ability to discriminate normal controls from dementia. The QDRS-generated CDR demonstrated excellent correspondence with the CDR (ICC=0.90) and sum-of-boxes (ICC=0.92). DISCUSSION: The QDRS validly and reliably differentiates individuals with and without dementia and accurately stages dementia without extensive training or clinician input, and is highly correlated with our gold standard measures. The QDRS provides a rapid method to determine study eligibility; stage patients in clinical practice; and improve case ascertainment in population studies. PMID- 26140285 TI - Immune Tolerance Induction against Experimental Autoimmune Encephalomyelitis (EAE) Using A New PLP-B7AP Conjugate that Simultaneously Targets B7/CD28 Costimulatory Signal and TCR/MHC-II Signal. AB - Most of the current therapies used in the treatment of multiple sclerosis (MS) are either ineffective or have adverse side effects. As such, there is a need to develop better therapies that specifically target myelin-specific aberrant immune cells involved in CNS inflammation without compromising the general immune system. In the present study, we developed a new bifunctional peptide inhibitor (BPI) that is effective and specific. Our BPI (PLP-B7AP) is composed of an antigenic peptide from myelin proteolipid protein (PLP139-151) and a B7 antisense peptide (B7AP) derived from CD28 receptor. The main hypothesis is that PLP-B7AP simultaneously targets MHC-II and B7-costimulatory molecules on the surface of antigen presenting cells (APC) and possibly alters the differentiation of naive T cells from inflammatory to regulatory phenotypes. Results showed that PLP-B7AP was very effective in suppressing experimental autoimmune encephalomyelitis (EAE) compared to various controls in a mouse model. PLP-B7AP was effective when administered both before and after disease induction. Secreted cytokines from splenocytes isolated during periods of high disease severity and remission indicated that PLP-B7AP treatment induced an increased production of anti inflammatory cytokines and inhibited the production of pro-inflammatory cytokines. Further, analysis of cortical brain tissue sections showed that PLP B7AP treated mice had significantly lower demyelination compared to the control group. All these taken together indicate that the T cell receptor (TCR) and the CD28 receptor can be targeted simultaneously to improve efficacy and specificity of potential MS therapeutics. PMID- 26140286 TI - Terbium(III)/gold nanocluster conjugates: the development of a novel ratiometric fluorescent probe for mercury(II) and a paper-based visual sensor. AB - In this work, a novel ratiometric fluorescent probe was developed for rapid, highly accurate, sensitive and selective detection of mercury(II) (Hg(2+)) based on terbium(III)/gold nanocluster conjugates (Tb(3+)/BSA-AuNCs), in which bovine serum albumin capped gold nanoclusters (BSA-AuNCs) acted as the signal indicator and terbium(III) (Tb(3+)) was used as the build-in reference. Our proposed ratiometric fluorescent probe exhibited unique specificity toward Hg(2+) against other common environmentally and biologically important metal ions, and had high accuracy and sensitivity with a low detection limit of 1 nM. In addition, our proposed probe was effectively employed to detect Hg(2+) in the biological samples from the artificial Hg(2+)-infected rats. More significantly, an appealing paper-based visual sensor for Hg(2+) was designed by using filter paper embedded with Tb(3+)/BSA-AuNC conjugates, and we have further demonstrated its feasibility for facile fluorescent sensing of Hg(2+) in a visual format, in which only a handheld UV lamp is used. In the presence of Hg(2+), the paper-based visual sensor, illuminated by a handheld UV lamp, would undergo a distinct fluorescence color change from red to green, which can be readily observed with naked eyes even in trace Hg(2+) concentrations. The Tb(3+)/BSA-AuNC-derived paper based visual sensor is cost-effective, portable, disposable and easy-to-use. This work unveiled a facile approach for accurate, sensitive and selective measuring of Hg(2+) with self-calibration. PMID- 26140289 TI - Geriatric Nursing 2.0! PMID- 26140287 TI - Enhancing biological analyses with three dimensional field asymmetric ion mobility, low field drift tube ion mobility and mass spectrometry (MUFAIMS/IMS MS) separations. AB - Multidimensional high throughput separations are ideal for analyzing distinct ion characteristics simultaneously in one analysis. We report on the first evaluation of a platform coupling a high speed field asymmetric ion mobility spectrometry microchip (MUFAIMS) with drift tube ion mobility and mass spectrometry (IMS-MS). The MUFAIMS/IMS-MS platform was used to analyze biological samples and simultaneously acquire multidimensional FAIMS compensation fields, IMS drift times, and accurate ion masses for the detected features. These separations thereby increased the overall measurement separation power, resulting in greater information content and more complete characterization of the complex samples. The separation conditions were optimized for sensitivity and resolving power by the selection of gas compositions and pressures in the FAIMS and IMS separation stages. The resulting performance provided three dimensional separations, benefitting both broad complex mixture studies and targeted analyses by improving isomeric separations and allowing detection of species obscured by interfering peaks. PMID- 26140290 TI - Hybrid Energy Harvester Consisting of Piezoelectric Fibers with Largely Enhanced 20 V for Wearable and Muscle-Driven Applications. AB - We present a polyvinylidene fluoride (PVDF) nanogenerator (NG) with advantages of direct writing and in situ poling via near-field electrospinning (NFES), which is completely location addressable and substrate independent. The maximum output voltage reached 20 V from the three layers piled NGs with serial connections, and the maximum output current can exceed 390 nA with the parallel integration setup. Linear superposition and switching polarity of current and voltage tests were validated by the authentic piezoelectric output. Nanofiber (NF)-based devices with a length ~5 cm can be easily attached on the human finger under folding releasing at ~45 degrees , and the output voltage and current can reach 0.8 V and 30 nA, respectively. This work based on NFs can potentially have a huge impact on harvesting various external sources from mechanical energies. PMID- 26140291 TI - Relationships between evidence-based practice, quality improvement and clinical error experience of nurses in Korean hospitals. AB - AIM: This study investigated individual and work-related factors associated with nurses' perceptions of evidence-based practice (EBP) and quality improvement (QI), and the relationships between evidence-based practice, quality improvement and clinical errors. BACKGROUND: Understanding the factors affecting evidence based practice and quality improvement activities and their relationships with clinical errors is important for designing strategies to promote evidence-based practice, quality improvement and patient safety. METHOD: A cross-sectional survey was conducted with 594 nurses in two Korean teaching hospitals using the evidence-based practice Questionnaire and quality improvement scale developed in this study. RESULT: Four hundred and forty-three nurses (74.6%) returned the completed survey. Nurses' ages and educational levels were significantly associated with evidence-based practice scores whereas age and job position were associated with quality improvement scores. There were positive, moderate correlations between evidence-based practice and quality improvement scores. Nurses who had not made any clinical errors during the past 12 months had significantly higher quality improvement skills scores than those who had. CONCLUSION: The findings indicated the necessity of educational support regarding evidence-based practice and quality improvement for younger staff nurses who have no master degrees. Enhancing quality improvement skills may reduce clinical errors. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should consider the characteristics of their staff when implementing educational and clinical strategies for evidence-based practice and quality improvement. PMID- 26140292 TI - Rapidly enlarging low-grade fibromyxoid sarcoma with intracranial extension in a 5-year-old girl: case report. AB - Low-grade fibromyxoid sarcoma (LGFMS) is a rare mesenchymal tumor that is characterized by a benign histology but potentially aggressive clinical behavior, with a high rate of recurrence and metastasis. It primarily occurs in young adults in the extremities, inguinal area, neck, or chest wall. There are rare reports of intracranial LGFMS in adults. In this report, the authors present the case of a 5-year-old girl who presented with a rapidly enlarging frontal scalp mass. Pathological examination of the resected mass demonstrated LGFMS. To the authors' knowledge, this is the only reported case of intracranial LGFMS in a child. PMID- 26140293 TI - Genetic evolution, plasticity, and bet-hedging as adaptive responses to temporally autocorrelated fluctuating selection: A quantitative genetic model. AB - Adaptive responses to autocorrelated environmental fluctuations through evolution in mean reaction norm elevation and slope and an independent component of the phenotypic variance are analyzed using a quantitative genetic model. Analytic approximations expressing the mutual dependencies between all three response modes are derived and solved for the joint evolutionary outcome. Both genetic evolution in reaction norm elevation and plasticity are favored by slow temporal fluctuations, with plasticity, in the absence of microenvironmental variability, being the dominant evolutionary outcome for reasonable parameter values. For fast fluctuations, tracking of the optimal phenotype through genetic evolution and plasticity is limited. If residual fluctuations in the optimal phenotype are large and stabilizing selection is strong, selection then acts to increase the phenotypic variance (bet-hedging adaptive). Otherwise, canalizing selection occurs. If the phenotypic variance increases with plasticity through the effect of microenvironmental variability, this shifts the joint evolutionary balance away from plasticity in favor of genetic evolution. If microenvironmental deviations experienced by each individual at the time of development and selection are correlated, however, more plasticity evolves. The adaptive significance of evolutionary fluctuations in plasticity and the phenotypic variance, transient evolution, and the validity of the analytic approximations are investigated using simulations. PMID- 26140294 TI - Endoscopic diagnosis of an MRI-occult, low-grade glioma with ependymal dissemination. AB - A 21-year-old man presented with triventricular hydrocephalus due to a tectal mass. He underwent an endoscopic third ventriculostomy, and multiple nodules were identified at the floor of the third ventricle intraoperatively. Surgical pathology of one of these lesions demonstrated that the tissue represented a low grade astrocytoma. The case highlights the existing potential of neuroendoscopy to reveal neuroimaging-occult lesions, in spite of the significant advances of MRI. Furthermore, the combination of the age of the patient, the nonenhancing MRI appearance, and the multifocality of the lesions constitutes a rare and interesting neoplastic presentation within the brain. The constellation of findings likely represents dissemination of a low-grade tectal glioma via the CSF compartment. PMID- 26140295 TI - Quantitation of Dihydroxyacetone in Australian Leptospermum Nectar via High Performance Liquid Chromatography. AB - The nonperoxide antibacterial activity of New Zealand manuka honey originates from dihydroxyacetone (DHA) within Leptospermum scoparium nectar. This study determined if DHA was present within the nectar of four Australian Leptospermum species: L. laevigatum, L. polygalifolium, L. trinervium, and L. whitei. A rapid and convenient new method was developed, which quantitated DHA/sugar ratios (ppm). The DHA and sugars were derivatized with o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride and analyzed via RP-HPLC with diode array detection at two wavelengths (200 and 243 nm). DHA was detected in all L. whitei and L. polygalifolium samples, where DHA/sugar ratios ranged from 10169 to 24199 ppm and from 9321 to 20174 ppm, respectively. DHA was undetected in any of the L. laevigatum and L. trinervium samples, and nectar activity was <100 ppm. The results of this study have implications for the Australian beekeeping industry, as the findings indicated that not all species of Leptospermum will produce active honey. PMID- 26140297 TI - Validation of a French translation of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) and comparison with other language versions. AB - OBJECTIVE: To validate a French version of the speech, spatial, and qualities of hearing scale (SSQ), a subjective evaluation of patients' hearing disability, and to assess SSQ reproducibility across different language versions. DESIGN: The SSQ was translated in accordance with the principles of the 'Universalist approach' of cross-cultural adaptation of patient-reported outcome instruments. Scores from a normal-hearing and a hearing-impaired population were compiled and compared, whenever possible, with data from the literature, collected using other language versions. STUDY SAMPLE: One hundred normal-hearing subjects and 230 hearing impaired subjects. RESULTS: Good reproducibility of scores and inter-subject variability were obtained between several language versions, even if scores found using the French version were slightly lower than those obtained using Dutch or English versions. A comparison of factor analysis outcomes between the English and French versions confirmed good conceptual equivalence across languages and robustness of the SSQ for use in international settings. The three main subscales (speech, spatial, and qualities) confirmed their usefulness in assessing different aspects of hearing disability. CONCLUSION: This study validated a French-language version of the SSQ, and assessed the reproducibility of the SSQ across subject groups, administration modes, and different countries/languages, confirming its potential as an international standard for hearing disability evaluation. PMID- 26140296 TI - Quantifying the influence of measured and unmeasured individual differences on demography. AB - 1. Demographic rates can vary not only with measured individual characters like age, sex and mass but also with unmeasured individual variables like behaviour, genes and health. 2. Predictions from population models that include measured individual characteristics often differ from models that exclude them. Similarly, unmeasured individual differences have the potential to impact predictions from population models. However, unmeasured individual differences are rarely included in population models. 3. We construct stage- and age-structured models (where stage is mass) of a roe deer population, which are parameterized from statistical functions that either include, or ignore, unmeasured individual differences. 4. We found that mass and age structures substantially impacted model parameters describing population dynamics, as did temporal environmental variation, while unmeasured individual differences impacted parameters describing population dynamics to a much smaller extent once individual heterogeneity related to mass and age has been included in the model. We discuss how our assumptions (unmeasured individual differences only in mean trait values) could have influenced our findings and under what circumstances unmeasured individual differences could have had a larger impact on population dynamics. 5. There are two reasons explaining the relative small influence of unmeasured individual differences on population dynamics in roe deer. First, individual body mass and age both capture a large amount of individual differences in roe deer. Second, in large populations of long-lived animals, the average quality of individuals (independent of age and mass) within the population is unlikely to show substantial variation over time, unless rapid evolution is occurring. So even though a population consisting of high-quality individuals would have much higher population growth rate than a population consisting of low-quality individuals, the probability of observing a population consisting only of high-quality individuals is small. PMID- 26140299 TI - Conceptions of working life among employees with mild-moderate aided hearing impairment: A phenomenographic study. AB - OBJECTIVES: The aim was to explore the conceptions of working life among employees with mild-moderate aided hearing impairment (HI). DESIGN: This study has a descriptive design, in which data was collected by means of semi-structured interviews. All interviews were audio-recorded and transcribed verbatim. The text was analysed in accordance with the phenomenographic approach. STUDY SAMPLE: Fifteen participants with mild-moderate aided HI were recruited to the current study. RESULTS: The analysis of the interviews resulted in four main categories describing the participants' conceptions of working life: (1) diffiiculties in daily work, (2) communication strategies, (3) facilitating factors in work environment, and (4) impact on daily life. The four identified descriptive categories show that the effects of HI on the lives of working adults generate far-reaching psychosocial consequences for the individual. CONCLUSIONS: This study demonstrates that difficulties and impact of having a HI interact with strategies used by the individual and contextual facilitators made in the work environment. We argue that there is a need for extensive services in aural rehabilitation for this population. This includes identifying the need of assistive listening devices, teaching the individual with HI about communication strategies and informing stakeholders about the consequence of having a HI. PMID- 26140298 TI - An evaluation of the performance of two binaural beamformers in complex and dynamic multitalker environments. AB - OBJECTIVE: Binaural beamformers are super-directional hearing aids created by combining microphone outputs from each side of the head. While they offer substantial improvements in SNR over conventional directional hearing aids, the benefits (and possible limitations) of these devices in realistic, complex listening situations have not yet been fully explored. In this study we evaluated the performance of two experimental binaural beamformers. DESIGN: Testing was carried out using a horizontal loudspeaker array. Background noise was created using recorded conversations. Performance measures included speech intelligibility, localization in noise, acceptable noise level, subjective ratings, and a novel dynamic speech intelligibility measure. STUDY SAMPLE: Participants were 27 listeners with bilateral hearing loss, fitted with BTE prototypes that could be switched between conventional directional or binaural beamformer microphone modes. RESULTS: Relative to the conventional directional microphones, both binaural beamformer modes were generally superior for tasks involving fixed frontal targets, but not always for situations involving dynamic target locations. CONCLUSIONS: Binaural beamformers show promise for enhancing listening in complex situations when the location of the source of interest is predictable. PMID- 26140300 TI - Hearing-aid use and long-term health outcomes: Hearing handicap, mental health, social engagement, cognitive function, physical health, and mortality. AB - OBJECTIVE: To clarify the impact of hearing aids on mental health, social engagement, cognitive function, and physical health outcomes in older adults with hearing impairment. DESIGN: We assessed hearing handicap (hearing handicap inventory for the elderly; HHIE-S), cognition (mini mental state exam, trail making, auditory verbal learning, digit-symbol substitution, verbal fluency, incidence of cognitive impairment), physical health (SF-12 physical component, basic and instrumental activities of daily living, mortality), social engagement (hours per week spent in solitary activities), and mental health (SF-12 mental component) at baseline, five years prior to baseline, and five and 11 years after baseline. STUDY SAMPLE: Community-dwelling older adults with hearing impairment (N = 666) from the epidemiology of hearing loss study cohort. RESULTS: There were no significant differences between hearing-aid users and non-users in cognitive, social engagement, or mental health outcomes at any time point. Aided HHIE-S was significantly better than unaided HHIE-S. At 11 years hearing-aid users had significantly better SF-12 physical health scores (46.2 versus 41.2; p = 0.03). There was no difference in incidence of cognitive impairment or mortality. CONCLUSION: There was no evidence that hearing aids promote cognitive function, mental health, or social engagement. Hearing aids may reduce hearing handicap and promote better physical health. PMID- 26140301 TI - Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose dense rituximab in elderly patients with chronic lymphocytic leukemia. AB - Elderly patients with chronic lymphocytic leukemia (CLL) are underrepresented in trials evaluating fludarabine, cyclophosphamide, and rituximab (FCR). We assessed four cycles of FCR with two additional rituximab doses on day 14 of cycles 1 and 2 in 194 untreated CLL patients > 65 years (median age 71.2) without del17p. Four FCR cycles were administered to 90.7% (176/194), with (n = 74) or without (n = 102) dose-delay and/or dose-reduction. A total of 50% grade 3/4 neutropenia occurred after each cycle. Only 6.2% cycles were associated with severe infection. Complete remission (CR) was achieved in 19.7%, and partial remission (PR) in 73.9% of patients. Minimal residual disease (MRD) was negative in 36.7%. Overall survival at 36 months was estimated at 87.4%. Oral FC and dose-dense rituximab is feasible and active in fit elderly CLL patients. However, myelosuppression is significant and frequent dose adaptations are required implying that these results cannot be generalized to unfit or frail elderly CLL. PMID- 26140302 TI - Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine. AB - Mesenchymal stem cells (MSCs), which can be obtained from various organs and easily propagated in vitro, are one of the most extensively used types of stem cells and have been shown to be efficacious in a broad set of diseases. The unique and highly desirable properties of MSCs include high migratory capacities toward injured areas, immunomodulatory features, and the natural ability to differentiate into connective tissue phenotypes. These phenotypes include bone and cartilage, and these properties predispose MSCs to be therapeutically useful. In addition, MSCs elicit their therapeutic effects by paracrine actions, in which the metabolism of target tissues is modulated. Genetic engineering methods can greatly amplify these properties and broaden the therapeutic capabilities of MSCs, including transdifferentiation toward diverse cell lineages. However, cell engineering can also affect safety and increase the cost of therapy based on MSCs; thus, the advantages and disadvantages of these procedures should be discussed. In this review, the latest applications of genetic engineering methods for MSCs with regenerative medicine purposes are presented. PMID- 26140303 TI - Effect of breastfeeding on malocclusions: a systematic review and meta-analysis. AB - AIM: The objective of this systematic review was to investigate whether breastfeeding decreases the risk of malocclusions. METHODS: Six databases were systematically searched to the end of October 2014. Observational and interventional studies were included. Breastfeeding was evaluated in three categories: (i) ever versus never; (ii) exclusive versus absence of exclusive; and (iii) longer periods versus shorter periods. All types of malocclusion were considered as the outcome. Pooled adjusted odds ratio and its 95% confidence interval (95%CI) were obtained from meta-analyses. Heterogeneity was assessed with both the Q-test and the I-square. Funnel plots and Egger's test were employed to assess publication bias. RESULTS: Forty-eight studies were included in the systematic review, and 41 were included in the overall meta-analysis (n = 27 023 participants). Subjects who were ever breastfed were less likely to develop malocclusions than those never breastfed (OR 0.34; 95% CI 0.24; 0.48), those who were exclusively breastfed presented lower risk to present malocclusion than those with absence of exclusive breastfeeding (OR 0.54; 95% CI 0.38; 0.77), and subjects longer breastfed were less likely to have malocclusions than those shorter breastfed (OR 0.40; 95% CI 0.29; 0.54). CONCLUSION: Breastfeeding decreases the risk of malocclusions. PMID- 26140304 TI - The mediating roles of coping and adjustment in the relationship between personality and academic achievement. AB - BACKGROUND: Existing literature has documented relationships between personality traits and academic achievement as well as some of the mechanisms underlying these links. However, the pathways by which personality traits are associated with achievement during stressful educational circumstances require further investigation. AIMS: This study examined a model of the roles of conscientiousness and neuroticism in achievement during the typically stressful university transition, with a focus on coping strategies and academic adjustment to university as mediators in the putative chain of events linking the dispositional traits with achievement. SAMPLE: The sample comprised 498 first year students attending a metropolitan university in Australia. METHODS: A multiwave design was used with measures of the personality traits administered at the beginning of the semester, measures of coping administered 4 weeks thereafter, and data on academic adjustment collected mid-semester. Students' GPA data were retrieved at the end of the semester. RESULTS: In structural equations analyses, conscientiousness was associated with greater primary control engagement coping and lesser narrow disengagement coping, whereas the opposite was found for neuroticism. Furthermore, conscientiousness and neuroticism were indirectly associated with academic adjustment via the coping strategies, and the personality factors were also indirectly associated with achievement via the coping strategies and academic adjustment linked serially in three-path mediated sequences. CONCLUSIONS: The findings of this study replicate existing data concerning the direct and indirect relationships of personality with coping and adjustment, and extend these data by elucidating the pathways through which conscientiousness and neuroticism are linked with achievement during a typically stressful educational event. PMID- 26140305 TI - Preorganized Hydrogen Bond Donor Catalysts: Acidities and Reactivities. AB - Measured DMSO pKa values for a series of rigid tricyclic adamantane-like triols containing 0-3 trifluoromethyl groups (i.e., 3(0)-3(3)) are reported. The three compounds with CF3 substituents are similar or more acidic than acetic acid (pKa = 13.5 (3(1)), 9.5 (3(2)), 7.3 (3(3)) vs 12.6 (HOAc)), and the resulting hydrogen bond network enables a remote gamma-trifluoromethyl group to enhance the acidity as well as one located at the alpha-position. Catalytic abilities of 3(0)-3(3) were also examined. In a nonpolar environment a rate enhancement of up to 100 fold over flexible acyclic analogs was observed presumably due to an entropic advantage of the locked-in structure. Gas-phase acidities are found to correlate with the catalytic activity better than DMSO pKa values and appear to be a better measure of acidities in low dielectric constant media. These trends are reduced or reversed in polar solvents highlighting the importance of the reaction environment. PMID- 26140306 TI - Ring-Oven Washing Technique Integrated Paper-based Immunodevice for Sensitive Detection of Cancer Biomarker. AB - A paper-based microfluidic immunodevice has recently attracted considerable interest for point-of-care testing (POCT) and a washing procedure was used as a standard procedure in immunoassay to eliminate the nonspecific binding protein from a paper surface. However, the traditional washing method cannot get rid of the nonspecific binding protein more completely to get a lower background. In this work, a novel washing strategy with a ring-oven technique integrated on a paper-based immunodevice was presented, which can effectively wash a nonspecific binding protein and enable a low background for sensitive detection of the carcinoembryonic antigen (CEA). By immobilizing the antibody on the detection area and incorporating the temperature-controlled ring-oven under the paper-based device, the continuous washing solution can carry the nonspecific binding protein to the waste area freely by capillary force and then the waste area dried quickly by heating. The paper device, which is matched to the size of the ring-oven, is composed of eight microfluidic channels by the simple and rapid paper-cutting fabrication method. With the HRP-catalyzed 3,3',5,5'-tetramethylbenzidine (TMB) H2O2 colorimetric detection method, a lower detection limit of 0.03 ng/mL CEA can be obtained by enzyme-linked immunosorbent assay (ELISA). The washing efficiency for the nonspecific binding protein was improved a lot compared to the traditional washing methods, and the established paper-based device can be used in the determination of CEA in human serum with high sensitivity. The paper-based device provides a new washing strategy for sensitive immunoassay and point-of care diagnostics. PMID- 26140307 TI - Modified halloysite nanotubes and the alleviation of kidney damage induced by dietary zearalenone in swine. AB - The aims of this study were, first, to investigate the toxicity of zearalenone (ZEN) through the analysis of biochemical parameters, oxidative stress, pathological changes and inflammatory response in the kidney of gestation sows and offspring; and, second, to evaluate the efficacy of modified halloysite nanotubes (MHNTs) for the alleviation to the adverse effects induced by ZEN. This study focused on the period of organogenesis between days 35 and 70 of gestation, and treatments included (1) a control diet; (2) contaminated grain (50% control corn and 50% mouldy corn); and (3) contaminated grain (50% control corn and 50% mouldy corn) + 1% MHNTs. ZEN treatment significantly increased most of the biochemical parameters and inflammatory cytokines and degenerative changes in the kidney and induced oxidative damage in plasma, whereas the addition of MHNTs in combination with ZEN induced a re-establishment of the biochemical parameters, the plasma oxidative stress enzyme activities and the normal histology of the kidney. Thus, the data strongly suggest that the deleterious effects of ZEN can be significantly diminished by MHNTs. PMID- 26140309 TI - Conventional versus accelerated corneal collagen cross-linking in the treatment of keratoconus. AB - BACKGROUND: This study aims to compare the effect of conventional corneal collagen cross-linking (CXL) with accelerated corneal collagen cross-linking in treatment of keratoconus. DESIGN: A comparative interventional study was employed. PARTICIPANTS: Participants were consecutive cases of progressive keratoconus receiving either conventional (3 mW/cm(2) irradiance for 30 min) or accelerated CXL (9 mW/cm(2) irradiance for 10 min). METHODS: Clinical and topographic parameters were compared between the two groups. Postoperative corneal stromal demarcation line was measured using anterior segment optical coherence tomography. MAIN OUTCOME MEASURES: Clinical and topographic parameters such as corrected distant visual acuity (CDVA), maximum keratometry (Kmax), mean keratometry (Kmean), demarcation line depth were gathered from medical records. RESULTS: There were a total of 26 eyes with an average follow up of 13.9 +/- 6.3 months. Fourteen eyes received conventional CXL, and 12 eyes had accelerated CXL. In the conventional CXL group, CDVA improved significantly (P = 0.021). There was also a significant reduction in Kmax (P = 0.003) and Kmean (P = 0.002). In the accelerated CXL group, no significant changes were found in CDVA (P = 0.395), Kmax (P = 0.388) and Kmean (P = 0.952) postoperatively. A significantly greater reduction in Kmax and Kmean were seen in conventional CXL compared to its accelerated counterpart (P = 0.001 and 0.015, respectively). The demarcation line was deeper in eyes with conventional CXL (P = 0.013), and the depth correlated significantly with the change in Kmean (r = -0.432, P = 0.045). CONCLUSION: Conventional and accelerated CXL are effective in stabilizing keratoconus progression after a mean of 12 months. Patients undergoing conventional CXL showed clinical improvement with greater corneal flattening, which correlated with a deeper corneal stromal demarcation line. This current study is the first to report such correlation. PMID- 26140311 TI - Effects of food on pharmacokinetics of immediate release oral formulations. PMID- 26140312 TI - Facile synthesis of 1-trifluoromethylalkenes via the decarboxylation of alpha trifluoromethyl-beta-lactones. AB - DCC-mediated cyclodehydration of alpha-trifluoromethyl-beta-hydroxy acids provides alpha-trifluoromethylated beta-lactone intermediates, without loss of stereoselectivity. These lactones undergo facile decarboxylation providing a simple route to obtain both alkyl and aryl trifluoromethylated alkenes in excellent yields and stereoselectivity. PMID- 26140314 TI - Extending GP hours: can it be a wolf in sheep's clothing? PMID- 26140313 TI - De novo KCNT1 mutations in early-onset epileptic encephalopathy. AB - KCNT1 mutations have been found in epilepsy of infancy with migrating focal seizures (EIMFS; also known as migrating partial seizures in infancy), autosomal dominant nocturnal frontal lobe epilepsy, and other types of early onset epileptic encephalopathies (EOEEs). We performed KCNT1-targeted next-generation sequencing (207 samples) and/or whole-exome sequencing (229 samples) in a total of 362 patients with Ohtahara syndrome, West syndrome, EIMFS, or unclassified EOEEs. We identified nine heterozygous KCNT1 mutations in 11 patients: nine of 18 EIMFS cases (50%) in whom migrating foci were observed, one of 180 West syndrome cases (0.56%), and one of 66 unclassified EOEE cases (1.52%). KCNT1 mutations occurred de novo in 10 patients, and one was transmitted from the patient's mother who carried a somatic mosaic mutation. The mutations accumulated in transmembrane segment 5 (2/9, 22.2%) and regulators of K(+) conductance domains (7/9, 77.8%). Five of nine mutations were recurrent. Onset ages ranged from the neonatal period (<1 month) in five patients (5/11, 45.5%) to 1-4 months in six patients (6/11, 54.5%). A generalized attenuation of background activity on electroencephalography was seen in six patients (6/11, 54.5%). Our study demonstrates that the phenotypic spectrum of de novo KCNT1 mutations is largely restricted to EIMFS. PMID- 26140315 TI - Compression hosiery choices for managing chronic oedema. PMID- 26140316 TI - Optimising medication for Parkinson's disease patients with dysphagia. AB - In addition to movement disorders, Parkinson's disease (PD) is associated with several nonmotor symptoms, including dysphagia (swallowing difficulties). Dysphagia can make the consumption of solid medicines difficult, which potentially contributes to the poor adherence that is common among people with PD. However, patients may be reluctant to admit that they experience dysphagia. Community nurses should actively enquire into swallowing difficulties among all patients, not only those with PD, and should work with pharmacists and other members of the multidisciplinary team to help optimise medication management to help improve adherence. PMID- 26140317 TI - A narrative review of the theoretical foundations of loneliness. AB - Loneliness has been found to relate to a wide range of harmful health outcomes. The adverse effects of loneliness upon people's lives emphasise the importance of understanding its nature and process. A number of theoretical and conceptual foundations have been proposed by scholars and are discussed and reflected upon in this article. The discussion and understanding of loneliness theoretical foundations provide useful insights toward the interpretation of its occurrence. PMID- 26140318 TI - Supporting carers: a learning resource for community nurses. AB - In 2013, as part of the Queen's Nursing Institute (QNI) Carers Project, the QNI asked the 4M Learning Network to test the need for a learning resource to enable community nurses to support carers' health and wellbeing needs. In order to measure the learning needs of community nurses, the QNI undertook a literature review (Laing and Sprung, 2013). The 4M team commenced with desk research and extensive consultation using an online survey and workshops across England. The outcomes of this consultation informed the development of an open-access online learning resource for community nurses, with modules covering different aspects of the nurses' role in relation to carers, as well as a comprehensive resource directory and e-workbook. This resource was launched in March 2014. In response to the enthusiasm and positive feedback from the community nurses, two learning resources were launched in March 2015 for practice nurses and school nurses. An accompanying resource directory mobile application is currently being development and is due to be released in summer 2015. It should be noted that throughout the article, the term carers refers to informal carers, i.e. family or friends caring for a person at home; it does not refer to an employed care assistant or helper. PMID- 26140319 TI - Assessing quality of life in Welsh carers with and without back pain. AB - BACKGROUND: The author aimed to study the prevalence and characteristics of care provision in Welsh adults with and without back pain, as well as their quality of life. The study used a country-wide and population-based setting from an independent dataset. METHOD: Data were retrieved from and analysed in the Welsh Health Survey 2013. Information on demographics, lifestyle factors, regular care provision, and quality of life was obtained from household interviews. Chi-square tests, t-tests, and survey-weighted multinomial regression modelling were performed. RESULTS: Of 15,007 Welsh adults aged 16 years and above, 2751 (18.3%) reported they had been caring for a sick, disabled, or frail person. The carers tended to be between 40-74 years, female, had not obtained a bachelor's degree, with a body mass index>25, physically active, smokers, and living in indoor secondhand smoke households. People who lived in mid and western Wales tended to give care, compared with those who lived in southeast and north Wales. Carers with back pain experienced slight physical health and emotional problems, whereas carers without back pain experienced worse physical health and emotional problems, which could disrupt normal life. CONCLUSION: Nearly one in five Welsh adults, with or without back pain, have provided care for other people. Future socioeconomic structure, health policy, and nursing programmes to reinvest in long-term care, such as a national psychiatric care initiative, should be encouraged, to lessen mental suffering alongside chronic pains and to optimise adult mental health and quality of life in all people, with or without back pain. PMID- 26140320 TI - Assessing and teaching female intermittent self-catheterization. PMID- 26140321 TI - Reshaping Public Health Nursing in the Republic of Ireland. AB - Across the world, there are concerns about how nursing and midwifery services are delivered in community settings. In the Republic of Ireland (ROI), significant economic contraction since 2009 has resulted in a decrease in the number of personnel available at a time when the older and younger population has been increasing. The purpose of this article is to outline a change initiative made in one public health nursing service in the ROI. In this change process, public health nursing staff moved from generalist to specialist roles. Distinct teams were created to deal with clinical care and child health, welfare, and protection. A key feature of the clinical team was the utilisation of a corporate caseload approach. The change was prompted by a reduction in staffing numbers, vacant caseloads, and increasing clinical risks and activity. Initial response to the change from frontline staff, management, and patients has been positive. The main effects of the change were noted in caseload management, risk management, and increased focus on clinical supervision. An external evaluation of the change initiative was carried out in 2014. PMID- 26140322 TI - Understanding the Code: exceptions to the duty of patient confidentiality. AB - Last month's article considered the scope of a district nurse's duty to maintain the confidentiality of patient information under the Nursing and Midwifery Council (NMC) Code, their contract of employment, and the law. This month, Richard Griffith considers the exceptions to these duties and sets out when a district nurse would be justified in disclosing patient information. PMID- 26140323 TI - What about dignity? A professional discussion. PMID- 26140324 TI - Reviewing roles: nurses vs physician assistants. PMID- 26140325 TI - Does Overweight and Obesity Impact on Self-Rated Health? Evidence Using Instrumental Variables Ordered Probit Models. AB - This paper, for the first time, presents estimates of the causal impact of overweight and obesity on self-rated health (SRH) using instrumental variables (IV) econometric methods. While a number of previous studies have sought to better understand the determinants of SRH, there is no consensus in relation to the impact of overweight and obesity. Using data from a large nationally representative sample of Irish parents and their children, we estimate a range of ordered probit models to isolate the causal effect of overweight and obesity on SRH. Our data includes independently and objectively recorded weight and height measures for parents and their children and we instrument for parental body mass index (BMI) status using the BMI of a biological child. After controlling for a range of individual, socioeconomic, health and lifestyle related variables, we find that being overweight has a negligible impact on SRH, while being obese has a practically and statistically significant negative impact on SRH, with these effects most pronounced for those who are most obese. We find only minor differences in these effects across gender. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26140327 TI - The 2014 Most Influential Bioelectromagnetics Journal Paper by Citation Award. PMID- 26140326 TI - Mn(II) mediated degradation of artemisinin based on Fe3O4@MnSiO3-FA nanospheres for cancer therapy in vivo. AB - Artemisinin (ART) is a natural drug with potent anticancer activities related with Fe(2+) mediated cleavage of the endoperoxide bridge in ART. Herein, we reported that Mn(2+) could substitute for Fe(2+) to react with ART and generate toxic products, inducing a much higher anticancer efficiency. On this basis, we prepared pH-responsive Fe3O4@MnSiO3-FA nanospheres which can efficiently deliver hydrophobic ART into tumors in mice models. Mn(2+) was released in acidic tumor environments and intracellular lysosomes, interacting with ART to kill cancer cells. The ART-loaded nanocarriers could suppress tumor growth more efficiently than free ART, which could be further illustrated by magnetic resonance imaging (MRI). Histological analysis revealed that the drug delivery system had no obvious effect on the major organs of mice. ART has been reported to have lower toxicity than chemotherapeutics. The ART-loaded nanocarriers are promising to be used in improving the survival of chemotherapy patients, providing a novel method for clinical tumor therapy. PMID- 26140328 TI - Bioavailability-Based In Situ Remediation To Meet Future Lead (Pb) Standards in Urban Soils and Gardens. AB - Recently the Centers for Disease Control and Prevention lowered the blood Pb reference value to 5 MUg/dL. The lower reference value combined with increased repurposing of postindustrial lands are heightening concerns and driving interest in reducing soil Pb exposures. As a result, regulatory decision makers may lower residential soil screening levels (SSLs), used in setting Pb cleanup levels, to levels that may be difficult to achieve, especially in urban areas. This paper discusses challenges in remediation and bioavailability assessments of Pb in urban soils in the context of lower SSLs and identifies research needs to better address those challenges. Although in situ remediation with phosphate amendments is a viable option, the scope of the problem and conditions in urban settings may necessitate that SSLs be based on bioavailable rather than total Pb concentrations. However, variability in soil composition can influence bioavailability testing and soil amendment effectiveness. More data are urgently needed to better understand this variability and increase confidence in using these approaches in risk-based decision making, particularly in urban areas. PMID- 26140330 TI - Single-Site Zeolite-Anchored Organoiridium Carbonyl Complexes: Characterization of Structure and Reactivity by Spectroscopy and Computational Chemistry. AB - A family of HY zeolite-supported cationic organoiridium carbonyl complexes was formed by reaction of Ir(CO)2 (acac) (acac=acetylacetonate) to form supported Ir(CO)2 complexes, which were treated at 298 K and 1 atm with flowing gas-phase reactants, including C2 H4 , H2 , (12) CO, (13) CO, and D2 O. Mass spectrometry was used to identify effluent gases, and infrared and X-ray absorption spectroscopies were used to characterize the supported species, with the results bolstered by DFT calculations. Because the support is crystalline and presents a nearly uniform array of bonding sites for the iridium species, these were characterized by a high degree of uniformity, which allowed a precise determination of the species involved in the replacement, for example, of one CO ligand of each Ir(CO)2 complex with ethylene. The supported species include the following: Ir(CO)2 , Ir(CO)(C2 H4)2 , Ir(CO)(C2 H4), Ir(CO)(C2 H5), and (tentatively) Ir(CO)(H). The data determine a reaction network involving all of these species. PMID- 26140331 TI - Chemical composition and antibacterial activity of essential oil of Nepeta graciliflora Benth. (Lamiaceae). AB - The chemical composition of the essential oil obtained from aerial parts of Nepeta graciliflora was analysed, for the first time, by GC-FID and GC-MS. A total of 27 compounds were identified, constituting over 91.44% of oil composition. The oil was strongly characterised by sesquiterpenes (86.72%), with beta-sesquiphellandrene (28.75%), caryophyllene oxide (12.15%), alpha-bisabolol (8.97%), alpha-bergamotene (8.51%), beta-bisabolene (6.33%) and beta Caryophyllene (5.34%) as the main constituents. The in vitro activity of the essential oil was determined against four micro-organisms in comparison with chloramphenicol by the agar well diffusion and broth dilution method. The oil exhibited good activity against all tested organisms. PMID- 26140329 TI - Optogenetic feedback control of neural activity. AB - Optogenetic techniques enable precise excitation and inhibition of firing in specified neuronal populations and artifact-free recording of firing activity. Several studies have suggested that optical stimulation provides the precision and dynamic range requisite for closed-loop neuronal control, but no approach yet permits feedback control of neuronal firing. Here we present the 'optoclamp', a feedback control technology that provides continuous, real-time adjustments of bidirectional optical stimulation in order to lock spiking activity at specified targets over timescales ranging from seconds to days. We demonstrate how this system can be used to decouple neuronal firing levels from ongoing changes in network excitability due to multi-hour periods of glutamatergic or GABAergic neurotransmission blockade in vitro as well as impinging vibrissal sensory drive in vivo. This technology enables continuous, precise optical control of firing in neuronal populations in order to disentangle causally related variables of circuit activation in a physiologically and ethologically relevant manner. PMID- 26140332 TI - Impressive Response to Dose-Dense Chemotherapy in a Patient with NUT Midline Carcinoma. AB - BACKGROUND: NUT midline carcinoma (NMC) is a rare, highly lethal malignancy that results from a chromosome translocation and mostly arises in the midline organs. To date, no treatment has been established. Most patients receive combinations of chemotherapy regimens and radiation, and occasionally subsequent resection; nevertheless, patients have an average survival hardly exceeding 7 months. CASE REPORT: A 21-year-old patient was admitted to our division with a large mediastinal mass with lung nodules, multiple vertebral metastases, and massive nodal involvement. In a few days, the patient developed a superior vena cava syndrome and an acute respiratory failure. Due to the rapid course of the disease, based on preliminary histology of poorly differentiated carcinoma, a dose-dense biweekly chemotherapy with paclitaxel, ifosfamide, and cisplatin was started. In the meantime, the diagnosis of NMC was confirmed. A surprising clinical benefit was obtained after the first cycle of chemotherapy, and after 6 cycles a PET-CT scan showed a very good response. At this point, radiotherapy was started but the disease progressed outside of the radiation field. The patient entered into a compassionate use protocol with Romidepsin, but a PET/CT scan after the first course showed disease progression with peritoneal and retroperitoneal carcinosis. A treatment with Pemetrexed was then started but the patient eventually died with rapid progressive disease. CONCLUSIONS: Our case history adds some interesting findings to available knowledge: NMC can be chemosensitive and radiosensitive. This opens the possibility to study more aggressive treatments, including high-dose consolidation chemotherapy and to evaluate the role of biological agents as maintenance treatments. PMID- 26140333 TI - Tissue-specific up-regulation of arginase I and II induced by p38 MAPK mediates endothelial dysfunction in type 1 diabetes mellitus. AB - BACKGROUND AND PURPOSE: Emerging evidence suggests a selective up-regulation of arginase I in diabetes causing coronary artery disease; however, the mechanisms behind this up-regulation are still unknown. Activated p38 MAPK has been reported to increase arginase II in various cardiovascular diseases. We therefore tested the role of p38 MAPK in the regulation of arginase I and II expression and its effect on endothelial dysfunction in diabetes mellitus. EXPERIMENTAL APPROACH: Endothelial function was determined in septal coronary (SCA), left anterior descending coronary (LAD) and mesenteric (MA) arteries from healthy and streptozotocin-induced diabetic Wistar rats by wire myographs. Arginase activity and protein levels of arginase I, II, phospho-p38 MAPK and phospho-endothelial NOS (eNOS) (Ser(1177) ) were determined in these arteries from diabetic and healthy rats treated with a p38 MAPK inhibitor in vivo. KEY RESULTS: Diabetic SCA and MA displayed impaired endothelium-dependent relaxation, which was prevented by arginase and p38 MAPK inhibition while LAD relaxation was not affected. Arginase I, phospho-p38 MAPK and eNOS protein expression was increased in diabetic coronary arteries. In diabetic MA, however, increased expression of arginase II and phospho-p38 MAPK, increased arginase activity and decreased expression of eNOS were observed. All these effects were reversed by p38 MAPK inhibition. CONCLUSIONS AND IMPLICATIONS: Diabetes-induced activation of p38 MAPK causes endothelial dysfunction via selective up-regulation of arginase I expression in coronary arteries and arginase II expression in MA. Therefore, regional differences appear to exist in the arginase isoforms contributing to endothelial dysfunction in type 1 diabetes mellitus. PMID- 26140334 TI - Digital adaptive optics line-scanning confocal imaging system. AB - A digital adaptive optics line-scanning confocal imaging (DAOLCI) system is proposed by applying digital holographic adaptive optics to a digital form of line-scanning confocal imaging system. In DAOLCI, each line scan is recorded by a digital hologram, which allows access to the complex optical field from one slice of the sample through digital holography. This complex optical field contains both the information of one slice of the sample and the optical aberration of the system, thus allowing us to compensate for the effect of the optical aberration, which can be sensed by a complex guide star hologram. After numerical aberration compensation, the corrected optical fields of a sequence of line scans are stitched into the final corrected confocal image. In DAOLCI, a numerical slit is applied to realize the confocality at the sensor end. The width of this slit can be adjusted to control the image contrast and speckle noise for scattering samples. DAOLCI dispenses with the hardware pieces, such as Shack-Hartmann wavefront sensor and deformable mirror, and the closed-loop feedbacks adopted in the conventional adaptive optics confocal imaging system, thus reducing the optomechanical complexity and cost. Numerical simulations and proof-of-principle experiments are presented that demonstrate the feasibility of this idea. PMID- 26140335 TI - The two-pore domain K2 P channel TASK2 drives human NK-cell proliferation and cytolytic function. AB - Natural killer (NK) cells are a subset of cytotoxic lymphocytes that recognize and kill tumor- and virus-infected cells without prior stimulation. Killing of target cells is a multistep process including adhesion to target cells, formation of an immunological synapse, and polarization and release of cytolytic granules. The role of distinct potassium channels in this orchestrated process is still poorly understood. The current study reveals that in addition to the voltage gated KV 1.3 and the calcium-activated KCa 3.1 channels, human NK cells also express the two-pore domain K2 P channel TASK2 (TWIK-related acid-sensitive potassium channel). Expression of Task2 varies among NK-cell subsets and depends on their differentiation and activation state. Despite its different expression in TASK2(high) CD56(bright) CD16(-) and TASK2(low) CD56(dim) CD16(+) NK cells, TASK2 is involved in cytokine-induced proliferation and cytolytic function of both subsets. TASK2 is crucial for leukocyte functional antigen (LFA-1) mediated adhesion of both resting and cytokine-activated NK cells to target cells, an early step in killing of target cells. With regard to the following mechanism, TASK2 plays a role in release of cytotoxic granules by resting, but not IL-15 induced NK cells. Taken together, our data exhibit two-pore potassium channels as important players in NK-cell activation and effector function. PMID- 26140336 TI - 'Rule your condition, don't let it rule you': young adults' sense of mastery in their accounts of growing up with a chronic illness. AB - Poor control of chronic illness is often attributed to patients' non-adherence to medical advice and treatment. Policy and practice has traditionally focused on improving adherence, assuming that the more patients comply, the better their control and outcomes will be. Drawing on complexity theory, we question this logic in a secondary analysis of qualitative data from studies of young adults' experiences of growing up with a chronic illness. Examining their sense of mastery of their condition, we found they valued both being in medical control of their condition and having autonomy but had different ideas about how to achieve these goals. While some young adults mostly shared the traditional medical view that achieving good control was the key to retaining their autonomy, others saw control and autonomy as independent, non-linear and potentially conflicting goals. The latter endeavoured to achieve both goals by striking a balance, variously adopting strategies of engagement with and resistance to their regime in the changing social contexts of their lives. We suggest that policy and practice needs to do more to promote autonomy and adaptive capacity, rather than simply maximising adherence and control, recognising the mundane complexity of living with and managing a chronic illness. PMID- 26140337 TI - Consecutive monitoring of faecal calprotectin during mesalazine suppository therapy for active rectal inflammation in ulcerative colitis. AB - BACKGROUND: No studies have monitored the levels of faecal calprotectin (FC) during mesalazine suppository therapy for proctitis in ulcerative colitis (UC). AIMS: To evaluate the value of consecutive monitoring of FC in patients with UC during mesalazine suppository therapy. METHODS: One hundred and sixty patients with active inflammation limited to the rectum were treated with mesalazine 1 g suppository once daily for 8 weeks. Patients who achieved clinical remission were advised to maintain the treatment, and were followed up for further 40 weeks. FC levels were measured every 8 weeks during the study. RESULTS: At week 8, 118 patients (74%) went into clinical remission, of whom 88 achieved endoscopic healing. The median FC level significantly decreased in patients with clinical and endoscopic remission (both P < 0.0001), while it did not change significantly in those without remission. Eighty (68%) of the 118 patients with remission continued the treatment. Twenty-four patients (30%) relapsed during the 40-week follow-up. In patients with clinical relapse, the median FC level elevated already 8 weeks before the diagnosis of relapse. In contrast, in patients who maintained remission it remained at a low level and did not significantly change during the follow-up. Elevated FC level (>=55 MUg/g) was useful for the early diagnosis of relapse (88% sensitivity and 80% specificity). CONCLUSIONS: Faecal calprotectin may represent a useful biomarker for the assessment of disease activity in UC patients treated with mesalazine suppositories. Serial monitoring of faecal calprotectin appears to be valuable for the prediction and early diagnosis of relapse during maintenance therapy. PMID- 26140339 TI - Efficacy of Zero-Profile Implant in Anterior Fusion to Treat Degenerative Cervical Spine Disease: Comparison with Techniques Using Bone Graft and Anterior Plating. AB - BACKGROUND: The efficacy of anterior fusion using zero-profile implant (Zero-P) in the surgical treatment of degenerative cervical disease was investigated through radiographic and clinical comparisons with existing treatments using autograft or allograft and anterior plating. MATERIAL AND METHODS: A total of 130 patients who underwent anterior decompression and fusion for degenerative cervical spine disease with a follow-up of at least 1 year were analyzed retrospectively. The cases were divided into three groups: autograft and plate (38 cases, group A), allograft and plate (44 cases, group B), and Zero-P (48 cases, group C). Maintenance of lordosis, extent of subsidence, and fusion were evaluated radiologically and compared among preoperative, postoperative, and final follow-up time points. In addition, changes in Visual Analog Scale (VAS) and Neurologic Disability Index (NDI) scores and the presence of complications were evaluated for clinical analysis. RESULTS: Operation time was significantly less in group C (p = 0.007, 0.002). Maintenance of entire and segmental lordosis after surgery was better in groups A and B compared with group C (p = 0.002, 0.001); however, the extent of loss of lordosis from the surgery to the final follow-up did not show any significant differences. Regarding the extent of subsidence, the increase of height between the vertebral bodies after the surgery was 3.10, 2.89, and 2.68 mm in group A, group B, and group C, respectively (p = 0.14), and changed to - 1.27, - 2.41, and - 1.2 mm at the final follow-up (p = 0.012). VAS and NDI scores were improved from 7.2 to 3 and 34 to 12, respectively, but there were no significant differences. Nonunion occurred in two cases in both group B and group C. In terms of clinical complications, two cases of persistent donor site pain were found in group A; one case of persistent dysphagia was found in both group A and group B. CONCLUSION: Anterior cervical fusion using Zero-P has a shorter operation time and less subsidence compared with conventional surgical techniques. Thus it can be considered a useful technique for the surgical treatment of degenerative cervical disease. PMID- 26140338 TI - The novel PAR2 ligand C391 blocks multiple PAR2 signalling pathways in vitro and in vivo. AB - BACKGROUND AND PURPOSE: Proteinase-activated receptor-2 (PAR2) is a GPCR linked to diverse pathologies, including acute and chronic pain. PAR2 is one of the four PARs that are activated by proteolytic cleavage of the extracellular amino terminus, resulting in an exposed, tethered peptide agonist. Several peptide and peptidomimetic agonists, with high potency and efficacy, have been developed to probe the functions of PAR2, in vitro and in vivo. However, few similarly potent and effective antagonists have been described. EXPERIMENTAL APPROACH: We modified the peptidomimetic PAR2 agonist, 2-furoyl-LIGRLO-NH2 , to create a novel PAR2 peptidomimetic ligand, C391. C391 was evaluated for PAR2 agonist/antagonist activity to PAR2 across Gq signalling pathways using the naturally expressing PAR2 cell line 16HBE14o-. For antagonist studies, a highly potent and specific peptidomimetic agonist (2-aminothiazo-4-yl-LIGRL-NH2 ) and proteinase agonist (trypsin) were used to activate PAR2. C391 was also evaluated in vivo for reduction of thermal hyperalgesia, mediated by mast cell degranulation, in mice. KEY RESULTS: C391 is a potent and specific peptidomimetic antagonist, blocking multiple signalling pathways (Gq -dependent Ca2+ , MAPK) induced following peptidomimetic or proteinase activation of human PAR2. In a PAR2-dependent behavioural assay in mice, C391 dose-dependently (75 MUg maximum effect) blocked the thermal hyperalgesia, mediated by mast cell degranulation. CONCLUSIONS AND IMPLICATIONS: C391 is the first low MW antagonist to block both PAR2 Ca2+ and MAPK signalling pathways activated by peptidomimetics and/or proteinase activation. C391 represents a new molecular structure for PAR2 antagonism and can serve as a basis for further development for this important therapeutic target. PMID- 26140340 TI - Real-time Monitoring of the Lateral Spread Response Resulting from Serial Decompression for Hemifacial Spasm Caused by a Fusiform Aneurysm. AB - Fusiform aneurysm as a cause of hemifacial spasm (HFS) is an extremely rare condition. A 69-year-old man developed paroxysmal spasm of his left side facial muscles over a period of 5 years. Radiologic images demonstrated a left vertebral artery (VA) fusiform aneurysm compressing the root entry zone of the left facial nerve. The patient underwent serial surgical procedures for the treatment of HFS under intraoperative electromyography monitoring. Lateral spread response (LSR) did not disappear despite 5 minutes of extracranial left VA ligation and remained after cerebrospinal fluid drainage after dura opening. After interposition of the VA through Teflon felt insertion, the LSR finally disappeared. The patient became symptom free immediately after the surgery and continued as such throughout a follow-up period of 1 year. This is the first report involving real-time monitoring of the LSR changes resulting from serial procedures of decompression in an HFS caused by a fusiform aneurysm of the VA. PMID- 26140341 TI - Commentary: "The Future of Spinal Cord Stereotaxy: An overview". PMID- 26140342 TI - The safety of human pluripotent stem cells in clinical treatment. AB - Human pluripotent stem cells (hPSCs) have practically unlimited proliferation potential and a capability to differentiate into any cell type in the human body. Since the first derivation in 1998, they have been an attractive source of cells for regenerative medicine. Numerous ethical, technological, and regulatory complications have been hampering hPSC use in clinical applications. Human embryonic stem cells (ESCs), parthenogenetic human ESCs, human nuclear transfer ESCs, and induced pluripotent stem cells are four types of hPSCs that are different in many clinically relevant features such as propensity to epigenetic abnormalities, generation methods, and ability for development of autologous cell lines. Propensity to genetic mutations and tumorigenicity are common features of all pluripotent cells that complicate hPSC-based therapies. Several recent advances in methods of derivation, culturing, and monitoring of hPSCs have addressed many ethical concerns and technological challenges in development of clinical-grade hPSC lines. Generation of banks of such lines may be useful to minimize immune rejection of hPSC-derived allografts. In this review, we discuss different sources of hPSCs available at the moment, various safety risks associated with them, and possible solutions for successful use of hPSCs in the clinic. We also discuss ongoing clinical trials of hPSC-based treatments. PMID- 26140343 TI - Erratum. PMID- 26140344 TI - Is Daytime Systolic Load an Important Risk Factor for Target Organ Damage in Pediatric Hypertension? AB - The aim of this study was to compare ambulatory blood pressure (BP) monitoring (ABPM) data and determine which hypertension type is a risk factor in target organ damage. A total of 82 children (47 boys) with suspected hypertension based on office BP measurements and considered hypertensive by ABPM were studied. Target organ damage included the following: 35.3% hypertensive retinopathy, 25.6% microalbuminuria, 15.8% increased left ventricular mass index, 29.2% increased carotid intima-media thickness (cIMT), 24.3% high augmentation index (AIx), and 19.5% high pulse wave velocity (PWV). The association between BP load, PWV, and cIMT was statistically significant. There were significant correlations between daytime systolic BP load, PWV, AIx, and cIMT. A statistically significant difference was also detected between nighttime systolic BP load, PWV, and cIMT values and nighttime diastolic BP load levels and values of AIx and cIMT. There was also a statistically significant difference between the high level of nighttime diastolic BP load and cIMT. The authors found that target organ damage was seen more often in children with primary hypertension who had systolic loads. PMID- 26140345 TI - Improving Localization Accuracy: Successive Measurements Error Modeling. AB - Vehicle self-localization is an essential requirement for many of the safety applications envisioned for vehicular networks. The mathematical models used in current vehicular localization schemes focus on modeling the localization error itself, and overlook the potential correlation between successive localization measurement errors. In this paper, we first investigate the existence of correlation between successive positioning measurements, and then incorporate this correlation into the modeling positioning error. We use the Yule Walker equations to determine the degree of correlation between a vehicle's future position and its past positions, and then propose a -order Gauss-Markov model to predict the future position of a vehicle from its past positions. We investigate the existence of correlation for two datasets representing the mobility traces of two vehicles over a period of time. We prove the existence of correlation between successive measurements in the two datasets, and show that the time correlation between measurements can have a value up to four minutes. Through simulations, we validate the robustness of our model and show that it is possible to use the first-order Gauss-Markov model, which has the least complexity, and still maintain an accurate estimation of a vehicle's future location over time using only its current position. Our model can assist in providing better modeling of positioning errors and can be used as a prediction tool to improve the performance of classical localization algorithms such as the Kalman filter. PMID- 26140346 TI - A Sensitive and Selective Label-Free Electrochemical DNA Biosensor for the Detection of Specific Dengue Virus Serotype 3 Sequences. AB - Dengue fever is the most prevalent vector-borne disease in the world, with nearly 100 million people infected every year. Early diagnosis and identification of the pathogen are crucial steps for the treatment and for prevention of the disease, mainly in areas where the co-circulation of different serotypes is common, increasing the outcome of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Due to the lack of fast and inexpensive methods available for the identification of dengue serotypes, herein we report the development of an electrochemical DNA biosensor for the detection of sequences of dengue virus serotype 3 (DENV-3). DENV-3 probe was designed using bioinformatics software and differential pulse voltammetry (DPV) was used for electrochemical analysis. The results showed that a 22-m sequence was the best DNA probe for the identification of DENV-3. The optimum concentration of the DNA probe immobilized onto the electrode surface is 500 nM and a low detection limit of the system (3.09 nM). Moreover, this system allows selective detection of DENV-3 sequences in buffer and human serum solutions. Therefore, the application of DNA biosensors for diagnostics at the molecular level may contribute to future advances in the implementation of specific, effective and rapid detection methods for the diagnosis dengue viruses. PMID- 26140347 TI - Spectral and Image Integrated Analysis of Hyperspectral Data for Waxy Corn Seed Variety Classification. AB - The purity of waxy corn seed is a very important index of seed quality. A novel procedure for the classification of corn seed varieties was developed based on the combined spectral, morphological, and texture features extracted from visible and near-infrared (VIS/NIR) hyperspectral images. For the purpose of exploration and comparison, images of both sides of corn kernels (150 kernels of each variety) were captured and analyzed. The raw spectra were preprocessed with Savitzky-Golay (SG) smoothing and derivation. To reduce the dimension of spectral data, the spectral feature vectors were constructed using the successive projections algorithm (SPA). Five morphological features (area, circularity, aspect ratio, roundness, and solidity) and eight texture features (energy, contrast, correlation, entropy, and their standard deviations) were extracted as appearance character from every corn kernel. Support vector machines (SVM) and a partial least squares-discriminant analysis (PLS-DA) model were employed to build the classification models for seed varieties classification based on different groups of features. The results demonstrate that combining spectral and appearance characteristic could obtain better classification results. The recognition accuracy achieved in the SVM model (98.2% and 96.3% for germ side and endosperm side, respectively) was more satisfactory than in the PLS-DA model. This procedure has the potential for use as a new method for seed purity testing. PMID- 26140348 TI - Assigning Main Orientation to an EOH Descriptor on Multispectral Images. AB - This paper proposes an approach to compute an EOH (edge-oriented histogram) descriptor with main orientation. EOH has a better matching ability than SIFT (scale-invariant feature transform) on multispectral images, but does not assign a main orientation to keypoints. Alternatively, it tends to assign the same main orientation to every keypoint, e.g., zero degrees. This limits EOH to matching keypoints between images of translation misalignment only. Observing this limitation, we propose assigning to keypoints the main orientation that is computed with PIIFD (partial intensity invariant feature descriptor). In the proposed method, SIFT keypoints are detected from images as the extrema of difference of Gaussians, and every keypoint is assigned to the main orientation computed with PIIFD. Then, EOH is computed for every keypoint with respect to its main orientation. In addition, an implementation variant is proposed for fast computation of the EOH descriptor. Experimental results show that the proposed approach performs more robustly than the original EOH on image pairs that have a rotation misalignment. PMID- 26140349 TI - Preserving Smart Objects Privacy through Anonymous and Accountable Access Control for a M2M-Enabled Internet of Things. AB - As we get into the Internet of Things era, security and privacy concerns remain as the main obstacles in the development of innovative and valuable services to be exploited by society. Given the Machine-to-Machine (M2M) nature of these emerging scenarios, the application of current privacy-friendly technologies needs to be reconsidered and adapted to be deployed in such global ecosystem. This work proposes different privacy-preserving mechanisms through the application of anonymous credential systems and certificateless public key cryptography. The resulting alternatives are intended to enable an anonymous and accountable access control approach to be deployed on large-scale scenarios, such as Smart Cities. Furthermore, the proposed mechanisms have been deployed on constrained devices, in order to assess their suitability for a secure and privacy-preserving M2M-enabled Internet of Things. PMID- 26140350 TI - A Software Product Line Process to Develop Agents for the IoT. AB - One of the most important challenges of this decade is the Internet of Things (IoT), which aims to enable things to be connected anytime, anyplace, with anything and anyone, ideally using any path/network and any service. IoT systems are usually composed of heterogeneous and interconnected lightweight devices that support applications that are subject to change in their external environment and in the functioning of these devices. The management of the variability of these changes, autonomously, is a challenge in the development of these systems. Agents are a good option for developing self-managed IoT systems due to their distributed nature, context-awareness and self-adaptation. Our goal is to enhance the development of IoT applications using agents and software product lines (SPL). Specifically, we propose to use Self-StarMASMAS, multi-agent system) agents and to define an SPL process using the Common Variability Language. In this contribution, we propose an SPL process for Self-StarMAS, paying particular attention to agents embedded in sensor motes. PMID- 26140351 TI - Effects of poplar buds as an alternative to propolis on postharvest diseases control of strawberry fruits. AB - BACKGROUND: Botrytis cinerea and Rhizopus stolonifer, two main postharvest pathogens, cause great loss of strawberry fruits. Here, the effects of poplar buds extracts, a main plant source for Chinese propolis, on disease control were investigated in vitro and in vivo. RESULTS: The HPLC profile of poplar buds ethanol extract (PBEE) was almost identical to that of propolis ethanol extract (PEE), with the active flavonoids identified as pinocembrin, chrysin and galangin. PBEE exhibited similar inhibitory activities on spore germination of both pathogens compared with PEE, and PBEE also strongly inhibited the mycelial growth of the pathogens. In vivo, PBEE could effectively reduce decay of strawberry fruits stored at 13 degrees C. Although the weight loss was slightly increased, the contents of total soluble solid, titritable acid, vitamin C and total anthocyanins were significantly higher in PBEE treated fruits than those of the control. CONCLUSION: PBEE had the similar antifungal activity with propolis and had great potential as an alternative to propolis to control strawberry fruits diseases. PMID- 26140352 TI - Endofibrosis: an unusual cause of leg pain in an athlete. AB - Endofibrosis of the external iliac artery can occur as a rare complication of high endurance physical activities, particularly cycling, running, and rowing. Symptoms mimic claudication and typically occur with vigorous exercise and improve with rest. Patients can experience thigh pain, swelling and paresthesias in the affected extremity. The diagnosis of endofibrosis is often delayed given the patient's overall normal appearance and lack of significant medical history. This report outlines the presentation and evaluation of a case of endofibrosis of the external iliac artery in an otherwise healthy 42-year-old healthy woman. Her diagnosis was delayed for two years before appropriate diagnostic testing and subsequent surgical intervention allowed for return to a normal, active lifestyle. PMID- 26140353 TI - Iatrogenic urological triggers of autonomic dysreflexia: a systematic review. PMID- 26140354 TI - Gold(I)-catalysed cascade reactions in the synthesis of 2,3-fused indole derivatives. AB - A gold(I)-catalysed hydroaminative/arylative cascade for the efficient synthesis of a variety of indole-fused skeletons has been developed. Factors controlling the catalyst loading required in these transformations involving 1,3 unsubstituted indole intermediates have been revealed, allowing isolation of an unprecedented 1,3-dimetallated 3H-indole gold complex characterized by X-ray diffraction. PMID- 26140355 TI - Chemical Vapor Deposition of Monolayer Rhenium Disulfide (ReS2). AB - The direct synthesis of monolayer and multilayer ReS2 by chemical vapor deposition at a low temperature of 450 degrees C is reported. Detailed characterization of this material is performed using various spectroscopy and microscopy methods. Furthermore initial field-effect transistor characteristics are evaluated, which highlight the potential in being used as an n-type semiconductor. PMID- 26140356 TI - Versatile myeloid cell subsets contribute to tuberculosis-associated inflammation. AB - Tuberculosis (TB), a chronic bacterial infectious disease caused by Mycobacterium tuberculosis (Mtb), typically affects the lung and causes profound morbidity and mortality rates worldwide. Recent advances in cellular immunology emphasize the complexity of myeloid cell subsets controlling TB inflammation. The specialization of myeloid cell subsets for particular immune processes has tailored their roles in protection and pathology. Among myeloid cells, dendritic cells (DCs) are essential for the induction of adaptive immunity, macrophages predominantly harbor Mtb within TB granulomas and polymorphonuclear neutrophils (PMNs) orchestrate lung damage. However, within each myeloid cell population, diverse phenotypes with unique functions are currently recognized, differentially influencing TB pneumonia and granuloma functionality. More recently, myeloid derived suppressor cells (MDSCs) have been identified at the site of Mtb infection. Along with PMNs, MDSCs accumulate within the inflamed lung, interact with granuloma-residing cells and contribute to exuberant inflammation. In this review, we discuss the contribution of different myeloid cell subsets to inflammation in TB by highlighting their interactions with Mtb and their role in lung pathology. Uncovering the manifold nature of myeloid cells in TB pathogenesis will inform the development of future immune therapies aimed at tipping the inflammation balance to the benefit of the host. PMID- 26140357 TI - (18)F-Labeling of Aryl-SCF3, -OCF3 and -OCHF2 with [(18)F]Fluoride. AB - We report that halogenophilic silver(I) triflate permits halogen exchange (halex) nucleophilic (18)F-fluorination of aryl-OCHFCl, -OCF2Br and -SCF2Br precursors under mild conditions. This Ag(I)-mediated process allows for the first time access to a range of (18)F-labeled aryl-OCHF2, -OCF3 and -SCF3 derivatives, inclusive of [(18)F]riluzole. The (18)F-labeling of these medicinally important motifs expands the radiochemical space available for PET applications. PMID- 26140358 TI - Taste and move: glucose and peptide transporters in the gastrointestinal tract. AB - NEW FINDINGS: What is the topic of this review? Nutrient absorption in the gastrointestinal tract requires membrane proteins embedded in the apical membrane of epithelial cells that allow bulk quantities of nutrients, such as monosaccharides and amino acids, to be moved into epithelial cells. Very recently, a new function of the transporters as nutrient sensors mediating peptide hormone release from enteroendocrine cells has been discovered. What advances does it highlight? The review covers recent advances in membrane transporter functions for the absorption and sensing of dietary peptides and sugars and their putative interplay. Nutrient transporters are integral membrane proteins responsible for uptake into enterocytes and release of nutrients into the circulation. Absorption of food breakdown products, such as fatty acids, monosaccharides or amino acids, requires high-capacity transporters. In the case of glucose, amino acids and peptides, the transporters are electrogenic in nature, coupling substrate flux to ion movement. While glucose absorption is mediated by the Na(+)-dependent SGLT1 protein, uptake of short-chain peptides is mediated by the H(+)-coupled PEPT1 protein. Interestingly, both transporters were recently shown to fulfil an additional role as intestinal 'sensors' in enteroendocrine cells, mediating the release of gastrointestinal peptide hormones into the circulation. Sensing of D-glucose and of di- and tripeptides is particularly relevant for the secretion of the incretins glucose-dependent insulinotrophic polypeptide and glucagon-like peptide 1 that promote insulin output from beta-cells and mediate beta-cell protection. In addition to these sensing pathways, a variety of G-protein-coupled receptors are involved in sensing of intestinal contents. D-Glucose is sensed not only by SGLT1 but also by the sweet taste receptor T1R2/3 expressed in enteroendocrine cells. Activation of T1R2/3 increases SGLT1 levels and intestinal glucose absorption. Although T1R2/3 ligands, such as artificial sweeteners, were shown to elicit incretin secretion from enteroendocrine cell lines or in vitro in tissue preparations, convincing data that this is also relevant in vivo are missing to date. However, there is growing interest in targeting intestinal sensory pathways, involving receptors but also the 'transceptors' PEPT1 and SGLT1, by use of drugs or food constituents to elicit the beneficial effects of incretins on the pancreas and metabolic control. PMID- 26140359 TI - Neutral and ionic platinum compounds containing a cyclometallated chiral primary amine: synthesis, antitumor activity, DNA interaction and topoisomerase I cathepsin B inhibition. AB - The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives of chiral 1-(1-naphthyl)ethylamine are reported, namely cycloplatinated neutral complexes [PtCl{(R or S)-NH(2)CH(CH(3))C(10)H(6)}(L)] [L = SOMe(2) ( 1-R or 1-S ), L = PPh(3) (2-R or 2-S), L = P(4-FC(6)H(4))(3) (3-R), L = P(CH(2))(3)N(3)(CH(2))(3) (4-R)], cycloplatinated cationic complexes [Pt{(R) NH(2)CH(CH(3))C(10)H(6)}{L}]Cl [L = Ph(2)PCH(2)CH(2)PPh(2) (5-R), L = (C(6)F(5))(2)PCH(2)CH(2)P(C(6)F(5))(2) (6-R)] and the Pt(ii) coordination compound trans-[PtCl(2){(R)-NH(2)CH(CH(3))C(10)H(6)}(2)] (7-R). The X-ray molecular structure of 7-R is reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT 116 colon), cell cycle arrest and apoptosis, DNA interaction, topoisomerase I and cathepsin B inhibition, and Pt cell uptake of the studied compounds are presented. Remarkable cytotoxicity was observed for most of the synthesized Pt(ii) compounds regardless of (i) the absolute configuration R or S, and (ii) the coordinated/cyclometallated (neutral or cationic) nature of the complexes. The most potent compound 2-R (IC(50) = 270 nM) showed a 148-fold increase in potency with regard to cisplatin in HCT-116 colon cancer cells. Preliminary biological results point out to different biomolecular targets for the investigated compounds. Neutral cyclometallated complexes 1-R and 2-R, modify the DNA migration as cisplatin, cationic platinacycle 5-R was able to inhibit topoisomerase I-promoted DNA supercoiling, and Pt(ii) coordination compound 7-R turned out to be the most potent inhibitor of cathepsin B. Induction of G-1 phase ( 2-R and 5-R ), and S and G-2 phases (6-R) arrests are related to the antiproliferative activity of some representative compounds upon A-549 cells. Induction of apoptosis is also observed for 2-R and 6-R. PMID- 26140360 TI - Experimental Assessment and Future Applications of the Shikani Tracheostomy Speaking Valve. AB - PURPOSE: Tracheostomy speaking valve use may increase airflow resistance and work of breathing. It remains unclear which valve offers the best performance characteristics. We compared the performance characteristics of the Shikani speaking valve (SSV; unidirectional-flow ball valve) with those of the Passy-Muir valve (PMV; bias-closed flapper valve). METHOD: Airflow resistance was measured for both the SSV and the PMV at 8 flow amplitudes and in 3 orientations (-15 degrees , 0 degrees , +20 degrees ) in the bias-open and bias-closed configurations. RESULTS: Significantly lower airflow resistance was observed for the SSV (bias open) compared with the PMV at -15 degrees (p < .001), 0 degrees (p < .001), and +20 degrees (p = .006) from the horizon. No significant difference was observed between the PMV and the SSV (bias-closed) configuration at any of the tested angles. A nonsignificant trend toward decreased airflow resistance was observed between the SSV bias-open and bias-closed configurations at each of the angles tested. CONCLUSIONS: The SSV demonstrated lower airflow resistance compared with the PMV across 8 flow amplitudes in the bias-open configuration at -15 degrees , 0 degrees , and +20 degrees from the horizon. Further investigation is needed to determine the clinical impact of these findings on patient comfort, work of breathing, phonation, and airway protection during swallowing. PMID- 26140361 TI - Small polyanion recognition of a triazolium cyclodextrin click cluster in water. AB - In order to detect small polyanions (sPAs), which play important roles in many biological systems, a triazolium cyclodextrin click cluster (5, hexakis{6-(3 methyl-4-hydroxymethyl-1H-1,2,3-triazolium-1-yl)-6-deoxy}-alpha-cyclodextrin iodide) was synthesized and characterized. The competition binding to 5 occupied by 5-carboxyfluorescein of inositol-1,4,5-trisphosphate (IP3), phytic acid, adenosine triphosphate (ATP), ethylenediaminetetraacetic acid (EDTA), glucose, and glucose-6-phosphate was evaluated by UV/vis titration in HEPES (10 mM, pH 7.4) : methanol (1 : 1, v/v). We obtained the binding constants of IP3 and phytic acid to 5 (1.4 * 10(6) and 1.9 * 10(6) M(-1), respectively); however, the binding constants of ATP and EDTA were significantly lower (2.1 * 10(5) and 4.5 * 10(4) M(-1), respectively). Moreover, glucose and glucose-6-phosphate did not show any detectable binding. In addition, the sPA recognition of the triazolium cyclodextrin click cluster in water was confirmed by fluorescence titration. PMID- 26140364 TI - Investigation of Uranium Tris(imido) Complexes: Synthesis, Characterization, and Reduction Chemistry of [U(NDIPP)3(thf)3]. AB - Addition of KC8 to trivalent [UI3(thf)4] in the presence of three equivalents of 2,6-diisopropylphenylazide (N3DIPP) results in the formation of the hexavalent uranium tris(imido) complex [U(NDIPP)3(thf)3] (1) through a facile, single-step synthesis. The X-ray crystal structure shows an octahedral complex that adopts a facial orientation of the imido substituents. This structural trend is maintained during the single-electron reduction of 1 to form dimeric [U(NDIPP)3{K(Et2O)}]2 (2). Variable-temperature/field magnetization studies of 2 show two independent U(V) 5f (1) centers, with no antiferromagnetic coupling present. Characterization of these complexes was accomplished using single-crystal X-ray diffraction, variable-temperature (1)H NMR spectroscopy, as well as IR and UV/Vis absorption spectroscopic studies. PMID- 26140362 TI - Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer. AB - Cancer cells exhibit altered metabolism including aerobic glycolysis that channels several glycolytic intermediates into de novo purine biosynthetic pathway. We discovered increased expression of phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas. Transcript analyses from next-generation RNA sequencing and gene expression profiling studies suggested that PPAT and PAICS can serve as prognostic biomarkers for aggressive lung adenocarcinoma. Immunohistochemical analysis of PAICS performed on tissue microarrays showed increased expression with disease progression and was significantly associated with poor prognosis. Through gene knockdown and over-expression studies we demonstrate that altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Furthermore we identified genomic amplification and aneuploidy of the divergently transcribed PPAT-PAICS genomic region in a subset of lung cancers. We also present evidence for regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-Diazo-5-oxo-L-norleucine (DON) blocked glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity. In summary, this study reveals the regulatory mechanisms by which purine biosynthetic pathway enzymes PPAT and PAICS, and pyruvate kinase activity is increased and exposes an existing metabolic vulnerability in lung cancer cells that can be explored for pharmacological intervention. PMID- 26140365 TI - Remarkable Functional Convergence: Alarmone ppGpp Mediates Persistence by Activating Type I and II Toxin-Antitoxins. AB - In this issue of Molecular Cell, Verstraeten et al. (2015) demonstrate that the conserved GTPase Obg and the second messenger ppGpp mediate persistence by activation of a type I toxin-antitoxin module (hokB/sokB) in E. coli. PMID- 26140363 TI - Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo. AB - Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (~18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer. PMID- 26140366 TI - Approaching the Golden Fleece a Molecule at a Time: Biophysical Insights into Argonaute-Instructed Nucleic Acid Interactions. AB - Argonaute proteins act at the core of nucleic acid-guided interference pathways that regulate gene expression and defend organisms against foreign genetic elements in all domains of life. Here, we review recent biophysical studies on how Argonaute proteins instruct oligonucleotides in the process of target finding, binding, cleavage, and release, as measured at high spatiotemporal resolution by single-molecule approaches. In the context of previous structural, biochemical, and computational studies, a model emerges for how Argonaute proteins manipulate the thermodynamic rules for nucleic acid hybridization to convey efficiency and specificity to RNA- and DNA-guided regulatory processes. PMID- 26140367 TI - Human Argonaute 2 Has Diverse Reaction Pathways on Target RNAs. AB - Argonaute is a key enzyme of various RNA silencing pathways. We use single molecule fluorescence measurements to characterize the reaction mechanisms of the core-RISC (RNA-induced silencing complex) composed of human Argonaute 2 and a small RNA. We found that target binding of core-RISC starts at the seed region, resulting in four distinct reaction pathways: target cleavage, transient binding, stable binding, and Argonaute unloading. The target cleavage requires extensive sequence complementarity and dramatically accelerates core-RISC recycling. The stable binding of core-RISC is efficiently established with the seed match only, providing a potential explanation for the seed-match rule of miRNA (microRNA) target selection. Target cleavage on perfect-match targets sensitively depends on RNA sequences, providing an insight into designing more efficient siRNAs (small interfering RNAs). PMID- 26140368 TI - Single-Molecule Analysis of the Target Cleavage Reaction by the Drosophila RNAi Enzyme Complex. AB - Small interfering RNAs (siRNAs) direct cleavage of complementary target RNAs via an RNA-induced silencing complex (RISC) that contains Argonatute2 protein at its core. However, what happens after target cleavage remains unclear. Here we analyzed the cleavage reaction by Drosophila Argonaute2-RISC using single molecule imaging and revealed a series of intermediate states in target recognition, cleavage, and product release. Our data suggest that, after cleavage, RISC generally releases the 5' cleavage fragment from the guide 3' supplementary region first and then the 3' fragment from the seed region, highlighting the reinforcement of the seed pairing in RISC. However, this order can be reversed by extreme stabilization of the 3' supplementary region or mismatches in the seed region. Therefore, the release order of the two cleavage fragments is influenced by the stability in each region, in contrast to the unidirectional base pairing propagation from the seed to the 3' supplementary region upon target recognition. PMID- 26140369 TI - Concordance between Composite International Diagnostic Interview and self-reports of depressive symptoms: a re-analysis. AB - Concordance between sum scores of self-reported depressive symptoms and structured interview diagnoses has been studied extensively, but are these the best attainable self-report-based predictions for interview diagnoses? We maximized the cross-validated concordance between World Health Organization's Composite International Diagnostic Interview (CIDI) diagnosis and Beck's Depression Inventory (BDI), and General Health Questionnaire (GHQ), from the viewpoint of exploratory statistics, re-analysing Health 2000 general-population sample of adults over 30 years in mainland Finland (N = 5200-5435). BDI sum-score prediction of CIDI diagnosis could be superseded by using (1) weighted sums of items, (2) classification trees constructed from items, or (3) a single item. Best solution (2) yielded cross-validated Youden's Index 0.757 [standard error (SE) = 0.001, sensitivity = 0.907, specificity = 0.851], improving the concordance to 1.07-fold (1.18-fold for 12-month diagnosis). A single-item solution was best for the GHQ. All positive predictive values remained low (0.09 0.31). Thus, CIDI-to-questionnaire concordance can be improved by using all information in the questionnaires instead of just sum scores, but latent-trait theory for questionnaires is incompatible with interview diagnoses (single item achieved better concordance than summing all). Self-reports have low predictive value for CIDI diagnoses in the general population, but better in settings with higher major depressive disorder (MDD) base rates. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26140370 TI - The effects of different farm environments on the performance of Texel sheep. AB - In order to assess the extent of genotype by environment interactions (G*E) and environmental sensitivity in sheep farm systems, environmental factors must be identified and quantified, after which the relationship with the traits(s) of interest can be investigated. The objectives of this study were to develop a farm environment (FE) scale, using a canonical correlation analysis, which could then be used in linear reaction norm models. Fine-scale farm survey data, collected from a sample of 39 Texel flocks across the United Kingdom, was combined with information available at the national level. The farm survey data included information on flock size and concentrate feed use. National data included flock performance averages for 21-week-old weight (21WT), ultrasound back-fat (UFD) and muscle (UMD) depths, as well as regional climatic data. The FE scale developed was then combined with 181 555 (21WT), 175 399 (UMD) and 175 279 (UFD) records from lambs born between 1990 and 2011, on 494 different Texel flocks, to predict reaction norms for sires used within the population. A range of sire sensitivities estimated across the FE scale confirmed the presence of genetic variability as both 'plastic' and 'robust' genotypes were observed. Variations in heritability estimates were also observed indicating that the rate genetic progress was dependent on the environment. Overall, the techniques and approaches used in this study have proven to be useful in defining sheep FEs. The results observed for 21WT, UMD and UFD, using the reaction norm models, indicate that in order to improve genetic gain and flock efficiency, future genetic evaluations would benefit by accounting for the G*E observed. PMID- 26140372 TI - Cyclic voltammetry of fast conducting electrocatalytic films. AB - In the framework of contemporary energy challenges, cyclic voltammetry is a particularly useful tool for deciphering the kinetics of catalytic films. The case of fast conducting films is analyzed, whether conduction is of the ohmic type or proceeds through rapid electron hopping. The rate-limiting factors are then the diffusion of the substrate in solution and through the film as well as the catalytic reaction itself. The dimensionless combination of the characteristics of these factors allows reducing the number of actual parameters to a maximum of two. The kinetics of the system may then be fully analyzed with the help of a kinetic zone diagram. Observing the variations of the current potential responses with operational parameters such as film thickness, the potential scan rate and substrate concentration allows a precise assessment of the interplay between these factors and of the values of the rate controlling factors. A series of thought experiments is described in order to render the kinetic analysis more palpable. PMID- 26140371 TI - Analysis of mcDESPOT- and CPMG-derived parameter estimates for two-component nonexchanging systems. AB - PURPOSE: To compare the reliability and stability of the multicomponent-driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and Carl-Purcell Meiboom-Gill (CPMG) approaches to parameter estimation. METHODS: The stability and reliability of mcDESPOT and CPMG-derived parameter estimates were compared through examination of energy surfaces, evaluation of model sloppiness, and Monte Carlo simulations. Comparisons were performed on an equal time basis and assuming a two-component system. Parameter estimation bias, reflecting accuracy, and dispersion, reflecting precision, were derived for a range of signal-to-noise ratios (SNRs) and relaxation parameters. RESULTS: The energy surfaces for parameters incorporated into the mcDESPOT signal model exhibit flatness, a complex structure of local minima, and instability to noise to a much greater extent than the corresponding surfaces for CPMG. Although both mcDESPOT and CPMG performed well at high SNR, the CPMG approach yielded parameter estimates of considerably greater accuracy and precision at lower SNR. CONCLUSION: mcDESPOT and CPMG both permit high-quality parameter estimates under SNR that are clinically achievable under many circumstances, depending upon available hardware and resolution and acquisition time constraints. At moderate to high SNR, the mcDESPOT approach incorporating two-step phase increments can yield accurate parameter estimates while providing values for longitudinal relaxation times that are not available through CPMG. However, at low SNR, the CPMG approach is more stable and provides superior parameter estimates. Magn Reson Med 75:2406-2420, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26140373 TI - Conformational Dynamics of Ago-Mediated Silencing Processes. AB - Argonaute (Ago) proteins are key players of nucleic acid-based interference mechanisms. Their domains and structural organization are widely conserved in all three domains of life. However, different Ago proteins display various substrate preferences. While some Ago proteins are able to use several substrates, others are limited to a single one. Thereby, they were demonstrated to act specifically on their preferred substrates. Here, we discuss mechanisms of Ago-mediated silencing in relation to structural and biochemical insights. The combination of biochemical and structural information enables detailed analyses of the complex dynamic interplay between Ago proteins and their substrates. Especially, transient binding data allow precise investigations of structural transitions taking place upon Ago-mediated guide and target binding. PMID- 26140374 TI - Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy. AB - The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA. PMID- 26140376 TI - Bacterial Cellulose Production from Industrial Waste and by-Product Streams. AB - The utilization of fermentation media derived from waste and by-product streams from biodiesel and confectionery industries could lead to highly efficient production of bacterial cellulose. Batch fermentations with the bacterial strain Komagataeibacter sucrofermentans DSM (Deutsche Sammlung von Mikroorganismen) 15973 were initially carried out in synthetic media using commercial sugars and crude glycerol. The highest bacterial cellulose concentration was achieved when crude glycerol (3.2 g/L) and commercial sucrose (4.9 g/L) were used. The combination of crude glycerol and sunflower meal hydrolysates as the sole fermentation media resulted in bacterial cellulose production of 13.3 g/L. Similar results (13 g/L) were obtained when flour-rich hydrolysates produced from confectionery industry waste streams were used. The properties of bacterial celluloses developed when different fermentation media were used showed water holding capacities of 102-138 g . water/g . dry bacterial cellulose, viscosities of 4.7-9.3 dL/g, degree of polymerization of 1889.1-2672.8, stress at break of 72.3-139.5 MPa and Young's modulus of 0.97-1.64 GPa. This study demonstrated that by-product streams from the biodiesel industry and waste streams from confectionery industries could be used as the sole sources of nutrients for the production of bacterial cellulose with similar properties as those produced with commercial sources of nutrients. PMID- 26140377 TI - Stepchild or Prodigy? Neuroprotection in Multiple Sclerosis (MS) Research. AB - Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) and characterized by the infiltration of immune cells, demyelination and axonal loss. Loss of axons and nerve fiber pathology are widely accepted as correlates of neurological disability. Hence, it is surprising that the development of neuroprotective therapies has been neglected for a long time. A reason for this could be the diversity of the underlying mechanisms, complex changes in nerve fiber pathology and the absence of biomarkers and tools to quantify neuroregenerative processes. Present therapeutic strategies are aimed at modulating or suppressing the immune response, but do not primarily attenuate axonal pathology. Yet, target-oriented neuroprotective strategies are essential for the treatment of MS, especially as severe damage of nerve fibers mostly occurs in the course of disease progression and cannot be impeded by immune modulatory drugs. This review shall depict the need for neuroprotective strategies and elucidate difficulties and opportunities. PMID- 26140375 TI - Decellularized Human Skeletal Muscle as Biologic Scaffold for Reconstructive Surgery. AB - Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits) and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation. PMID- 26140378 TI - The UGG Isoacceptor of tRNAPro Is Naturally Prone to Frameshifts. AB - Native tRNAs often contain post-transcriptional modifications to the wobble position to expand the capacity of reading the genetic code. Some of these modifications, due to the ability to confer imperfect codon-anticodon pairing at the wobble position, can induce a high propensity for tRNA to shift into alternative reading frames. An example is the native UGG isoacceptor of E. coli tRNAPro whose wobble nucleotide U34 is post-transcriptionally modified to cmo5U34 to read all four proline codons (5'-CCA, 5'-CCC, 5'-CCG, and 5'-CCU). Because the pairing of the modified anticodon to CCC codon is particularly weak relative to CCA and CCG codons, this tRNA can readily shift into both the +1 and +2-frame on the slippery mRNA sequence CCC-CG. We show that the shift to the +2-frame is more dominant, driven by the higher stability of the codon-anticodon pairing at the wobble position. Kinetic analysis suggests that both types of shifts can occur during stalling of the tRNA in a post-translocation complex or during translocation from the A to the P-site. Importantly, while the +1-frame post complex is active for peptidyl transfer, the +2-frame complex is a poor peptidyl donor. Together with our recent work, we draw a mechanistic distinction between +1 and +2-frameshifts, showing that while the +1-shifts are suppressed by the additional post-transcriptionally modified m1G37 nucleotide in the anticodon loop, the +2-shifts are suppressed by the ribosome, supporting a role of the ribosome in the overall quality control of reading-frame maintenance. PMID- 26140379 TI - Impact of gas chromatography and mass spectrometry combined with gas chromatography and olfactometry for the sex differentiation of Baccharis articulata by the analysis of volatile compounds. AB - The Baccharis genus has more than 400 species of aromatic plants. However, only approximately 50 species have been studied in oil composition to date. From these studies, very few take into consideration differences between male and female plants, which is a significant and distinctive factor in Baccharis in the Asteraceae family. Baccharis articulata is a common shrub that grows wild in south Brazil, northern and central Argentina, Bolivia, Paraguay and Uruguay. It is considered to be a medicinal plant and is employed in traditional medicine. We report B. articulata male and female volatile composition obtained by simultaneous distillation-extraction technique and analyzed by gas chromatography with mass spectrometry. Also, an assessment of aromatic differences between volatile extracts was evaluated by gas chromatography with olfactometry. The results show a very similar chemical composition between male and female extracts, with a high proportion of terpene compounds of which beta-pinene, limonene and germacrene D are the main components. Despite the chemical similarity, great differences in aromatic profile were found: male plant samples exhibited the strongest odorants in number and intensity of aromatic attributes. These differences explain field observations which indicate differences between male and female flower aroma, and might be of ecological significance in the attraction of pollinating insects. PMID- 26140380 TI - Dexamethasone affects mouse olfactory mucosa gene expression and attenuates genes related to neurite outgrowth. AB - BACKGROUND: Olfaction is one of the important senses for humans. Systemic glucocorticoids are the most commonly used medications for olfactory loss because of their strong anti-inflammatory effects. However, their effect on olfactory function is still controversial and the precise mechanism is not clear. To gain a global view of the effect of systematic glucocorticoid treatment on gene expression in the olfactory mucosa (OM), we profiled these changes in a murine model of olfaction in order to identify underlying molecular mechanisms. METHODS: C57BL/6 mice were injected daily for 2 weeks (WK2) with dexamethasone (DEX, intraperitoneally, 1 mg/kg body weight) vs 1 day of DEX (D1) vs controls, which received saline (Ctrl) (n = 9/group). Total RNA from the OM was used to analyze global gene expression. Genes showing changes in expression were compared using the Database for Annotation, Visualization and Integrated Discovery (DAVID, v6.7) and the General Olfactory Sensitivity Database (GOSdb; http://genome.weizmann.ac.il/GOSdb). RESULTS: Between the WK2 and Ctrl groups, 3351 genes were differentially expressed, of which 236 genes were related to olfactory function. Genes involved in axon guidance, cell projection, and inflammation were enriched and overlapped significantly with those in the GOSdb. CONCLUSION: Systemic glucocorticoids exert effects on transcription of a notable number of genes in the OM and appear to orchestrate changes related to axon guidance, cell projection, and inflammation. Further examination may allow targeted therapies that lack the side effects of this category of medication. PMID- 26140381 TI - Opioid use and risk of liver fibrosis in HIV/hepatitis C virus-coinfected patients in Canada. AB - OBJECTIVES: Opioid use and opioid-related mortality have increased dramatically since the 1990s in North America. The effect of opioids on the liver is incompletely understood. Some studies have suggested that opioids cause liver damage and others have failed to show any harm. HIV/hepatitis C virus (HCV) coinfected persons may be particularly vulnerable to factors increasing liver fibrosis. We aimed to describe opioid use in an HIV/HCV-coinfected population in Canada and to estimate the association between opioid use and liver fibrosis. METHODS: We conducted a cross-sectional descriptive analysis of the Canadian Co infection Cohort Study data to characterize opioid use. We then conducted a longitudinal analysis to assess the average change in aspartate aminotransferase to-platelet ratio index (APRI) score associated with opioid use using a generalized estimating equation with linear regression. We assessed the progression to significant liver fibrosis (APRI >= 1.5) associated with opioid use with pooled logistic regression. RESULTS: In the 6 months preceding cohort entry, 32% of the participants had received an opioid prescription, 28% had used opioids illicitly and 18% had both received a prescription and used opioids illicitly. Neither prescribed nor illicit opioid use was associated with a change in the median APRI score [exp(beta) 0.99 (95% confidence interval (CI) 0.82, 1.12) and exp(beta) 0.95 (95% CI 0.81, 1.10), respectively] or with faster progression to liver fibrosis [hazard odds ratio (HOR) 1.20 (95% CI 0.73, 1.67) and HOR 1.09 (95% CI 0.63, 1.55), respectively]. CONCLUSIONS: Although opioids were commonly used both legally and illegally in our cohort, we were unable to demonstrate a negative impact on liver fibrosis progression. PMID- 26140382 TI - Mucosal and systemic immune responses induced by a single time vaccination strategy in mice. AB - Vaccination is considered by the World Health Organization as the most cost effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others. Contradictorily, few vaccines are of single dose and even less of mucosal administration. However, more common infections occur via mucosa, where secretory immunoglobulin A plays an essential role. As an alternative, we proposed a novel protocol of vaccination called Single Time Vaccination Strategy (SinTimVaS) by immunizing 2 priming doses at the same time: one by mucosal route and the other by parenteral route. Here, the mucosal and systemic responses induced by Finlay adjuvants (AF Proteoliposome 1 and AF Cochleate 1) implementing SinTimVaS in BALB/c mice were evaluated. One intranasal dose of AF Cochleate 1 and an intramuscular dose of AF Proteoliposome 1 adsorbed onto aluminum hydroxide, with bovine serum albumin or tetanus toxoid as model antigens, administrated at the same time, induced potent specific mucosal and systemic immune responses. Also, we demonstrated that SinTimVaS using other mucosal routes like oral and sublingual, in combination with the subcutaneous route elicits immune responses. SinTimVaS, as a new immunization strategy, could increase vaccination coverage and reduce time-cost vaccines campaigns, adding the benefits of immune response in mucosa. PMID- 26140383 TI - Susceptibility of northern corn rootworm Diabrotica barberi (Coleoptera: Chrysomelidae) to mCry3A and eCry3.1Ab Bacillus thuringiensis proteins. AB - The susceptibility of the northern corn rootworm Diabrotica barberi (Smith & Lawrence) to mCry3A and eCry3.1Ab proteins derived from Bacillus thuringiensis (Bt) was determined using a diet bioassay. Northern corn rootworm neonates were exposed to different concentrations of mCry3A and eCry3.1Ab, incorporated into artificial diet. Larval mortality was evaluated after 7 d. The mCry3A and eCry3.1Ab proteins were found to be toxic to the northern corn rootworm larvae. The LC50 and LC99 values for mCry3A were 5.13 and 2482.31 MUg/mL, respectively. For eCry3.1Ab, the LC50 and LC99 values were 0.49 and 213.01 MUg/mL. Based on the estimated lethal concentrations, eCry3.1Ab protein was more efficacious to northern corn rootworm larvae than mCry3A. These lethal concentration values will be used as diagnostic doses for routine annual monitoring for change in susceptibility of field collected northern corn rootworm to mCry3A, and eCry3.1Ab toxins. PMID- 26140384 TI - Aqueous Self-Assembly of Purely Hydrophilic Block Copolymers into Giant Vesicles. AB - Self-assembly of macromolecules is fundamental to life itself, and historically, these systems have been primitively mimicked by the development of amphiphilic systems, driven by the hydrophobic effect. Herein, we demonstrate that self assembly of purely hydrophilic systems can be readily achieved with similar ease and success. We have synthesized double hydrophilic block copolymers from polysaccharides and poly(ethylene oxide) or poly(sarcosine) to yield high molar mass diblock copolymers through oxime chemistry. These hydrophilic materials can easily assemble into nanosized (<500 nm) and microsized (>5 MUm) polymeric vesicles depending on concentration and diblock composition. Because of the solely hydrophilic nature of these materials, we expect them to be extraordinarily water permeable systems that would be well suited for use as cellular mimics. PMID- 26140385 TI - Coenzyme Q10 and fish oil synergistically alleviate aluminum chloride-induced suppression of testicular steroidogenesis and antioxidant defense. AB - Aluminum (Al) is an environmental xenobiotic that stimulates free radical generation and hence reproductive toxicity. Coenzyme Q10 (CoQ10) effectively counteracts free radical-induced tissue damage. Omega-3 polyunsaturated fatty acids present in fish oil (FO) exert beneficial effects on reproduction in male animals. This study therefore investigated the effects of both agents on testicular dysfunction induced by aluminum chloride (AlCl3). Fifty male rats were gavaged with either 1% gum acacia (control group) or AlCl3 (34 mg/kg/day) for ten weeks. Concurrently, AlCl3-treated rats received no treatment, CoQ10 (10 mg/kg/day, p.o.), and/or FO (400 mg/kg/day, p.o.) for ten weeks. AlCl3 caused a significant decrease in serum testosterone, luteinizing hormone (LH), and follicular stimulating hormone (FSH), as well as testicular weight, antioxidant enzyme gene expression and activities, reduced glutathione, zinc, adenosine 3',5' cyclic monophosphate (cAMP) contents, and number of Leydig cells, along with down regulation of 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-HSD, steroidogenic acute regulatory protein (STAR), and cholesterol side-chain cleavage enzyme (P450scc) gene expression. However, testicular Al, malondialdehyde (MDA), and nitric oxide (NO) levels were markedly increased. Treatment with CoQ10 and FO, alone or in combined form led to an improvement in the aforementioned biomarkers. Overall, individual or combined treatment with CoQ10 and FO could ameliorate the toxic effects of AlCl3 on testicular tissues by mechanisms related to their potent antioxidant potential and stimulatory effects on steroidogenic enzymes transcription. CoQ10 seems to be better than FO regarding oxidative and nitrosative stress, Zn deficiency, and Al overload. However, FO showed more pronounced effect than CoQ10 on hormones, steroidogenic markers, and cAMP. A cocktail of both demonstrated greater protective effects on testicular tissues than monotherapy. PMID- 26140386 TI - Exercise training restores oxidative stress and nitric oxide synthases in the rostral ventrolateral medulla of renovascular hypertensive rats. AB - We hypothesize that exercise training (EX) reverses the level of nitric oxide (NO) and oxidative stress into rostral ventrolateral medulla (RVLM) of renovascular hypertensive rats (two kidneys, one clip - 2K1C). Microinjections of L-arginine (5 nmol), L-NAME (10 nmol), or saline (100 nl) were made into RVLM of 2K1C and normotensive (SHAM) rats sedentary (SED) or subjected to swimming for 4 weeks. mRNA expression (by qRT-PCR) of nitric oxide synthases isoforms (nNOS, eNOS, and iNOS), manganese superoxide dismutase (MnSOD), copper and zinc superoxide (Cu/ZnSOD), catalase (CAT), NADPH oxidase subunit p22(phox), concentration of thiobarbituric acid-reactive substances (TBARS), and CAT activity into RVLM were evaluated. The mean arterial pressure was reduced in 2K1C EX compared with that in 2K1C SED rats. L-arginine into RVLM induced hypertensive effect in 2K1C and SHAM SED rats, while L-NAME prevented hypertensive effect only in SHAM-SED. EX reduced hypertensive effect of L-arginine in SHAM and 2K1C rats. mRNA expression of NOS isoforms, p22(phox), and concentration of TBARS were increased while CAT and Cu/ZnSOD expression and CAT activity decreased into RVLM of 2K1C-SED compared with SHAM-SED rats. Additionally, EX reversed mRNA expression of CAT and NOS isoforms, concentration of TBARS, and CAT activity into RVLM of 2K1C-EX rats. These data suggest that the levels of NOS and oxidative stress into RVLM are important to determine the level of hypertension. Furthermore, EX can restore the blood pressure by reversing the levels of NOS and CAT expression, and reducing TBARS concentration into RVLM for the physiological state. PMID- 26140387 TI - Outbreak of eczema and rhinitis in a group of office workers in Greenland. AB - INTRODUCTION: Disturbed indoor climate may in some cases be associated with illness. In the present paper, we report the results from a thorough investigation of office workers in Greenland, who developed skin and/or airway problems after moving into renewed offices. MATERIAL AND METHODS: In 2009 the office of the Bank of Greenland had a total renovation of the building, including new furniture and carpets. Symptoms developed within the first year after moving back into the renewed buildings. After removal of carpets in the building, symptoms significantly improved. Workers were examined in 2009 and re-examined in 2013, including clinical examination, patch test and when relevant also skin prick tests and histamine release test. Isothiazolinones and fumarates, both able to cause airway as well as skin symptoms, were isolated from carpets before testing, and included in the test series. RESULTS: In total, 32 out of 80 workers (40%) developed symptoms; 27 reported eczema, 20 rhinitis and 4 urticaria. Eczema was located on the hands and/or lower arms in 18 workers, on the face in 10 workers and on legs/trunk in 12 workers. After intervention in the office, 22 workers with eczema reported significant improvement, all cases of hand eczema cleared and 16 workers with rhinitis also improved. Positive patch tests to carpet extracts were found significantly more frequent in the worker cohort than in a control group comprising 47 dermatitis patients (p<0.001). Only few workers reacted with a positive response to skin prick test or in the HR test, no obvious pattern in reactions was found, and no conclusions can be made from these reactions. CONCLUSION: The results indicate that the reported symptoms are related to exposures from the building after renovation in 2009. A specific triggering exposure could not be identified, although chemicals from the glued carpets are suspected. The study is an example of a work place investigation, and illustrates the diversity of symptoms and exposures involved in "Sick Building" cases. PMID- 26140388 TI - Hemidiaphragmatic palsy following excision of cervical dumbbell neurofibroma in a patient with neurofibromatosis: Importance of assessing functional status of "non limb" roots. AB - A 27-year-old male patient with neurofibromatosis type 1 who was operated on for a dumbbell neurofibroma of the cervical spine developed transient respiratory difficulty due to postoperative unilateral diaphragmatic palsy. This report emphasizes the need for preoperative assessment of residual function in involved non-limb roots, the role of intraoperative monitoring to take a decision on root sacrifice, and the need for optimizing respiratory function preoperatively, and describes a complication rarely reported in literature. PMID- 26140390 TI - Cytotoxic monoterpenoid indole alkaloids isolated from the barks of Voacanga africana Staph. AB - A new monoterpenoid indole alkaloid compound (1) and six known monoterpenoid indole alkaloids compounds (2-7) were isolated from the barks of Voacanga africana Staph. The structures were established by spectral analysis as ibogamine 16-carboxylic acid,17,20-didehydro-5,6-dioxo-10-methoxy-methyl ester (1), voacamine (2), vobasine (3), voacangine (4), voacristine (5), 19-epi-voacristine (6) and 19-epi-heyneanine (7). Compound 1 was confirmed by X-ray crystallographic analysis. All of the isolated compounds were evaluated for cytotoxicity against five cell lines (HEPG-2, A375, MDA-MB-231, SH-SY5Y, CT26). Among them, compounds 2 and 6 displayed significant inhibitory activities, compounds 3, 4 and 5 showed moderate inhibitory activities, while compounds 1 and 7 showed no inhibitory activities against the five cell lines. PMID- 26140391 TI - Nanomaterial translocation--the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs--a review. AB - Engineered nanomaterials (NMs) offer great technological advantages but their risks to human health are still not fully understood. An increasing body of evidence suggests that some NMs are capable of distributing from the site of exposure to a number of secondary organs. The research into the toxicity posed by the NMs in these secondary organs is expanding due to the realisation that some materials may reach and accumulate in these target sites. The translocation to secondary organs includes, but is not limited to, the hepatic, central nervous, cardiovascular and renal systems. Current data indicates that pulmonary exposure is associated with low (inhalation route-0.00001-1% of total applied dose-24 h) translocation of virtually insoluble NMs such as iridium, carbon black, gold and polystyrene, while slightly higher translocation has been observed for NMs with either slow (e.g., silver, cerium dioxide and quantum dots) or fast (e.g., zinc oxide) solubility. The translocation of NMs following intratracheal, intranasal and pharyngeal aspiration is higher (up to 10% of administered dose), however the relevance of these routes for risk assessment is questionable. Uptake of the materials from the gastrointestinal tract seems to follow the same pattern as inhalation translocation, whereas the dermal uptake of NMs is generally reported to be low. The toxicological effects in secondary organs include oxidative stress, inflammation, cytotoxicity and dysfunction of cellular and physiological processes. For toxicological and risk evaluation, further information on the toxicokinetics and persistence of NMs is crucial. The overall aim of this review is to outline the data currently available in the literature on the biokinetics, accumulation, toxicity and eventual fate of NMs in order to assess the potential risks posed by NMs to secondary organs. PMID- 26140392 TI - Analysis of long-term (median 10.5 years) outcomes in children presenting with traumatic brain injury and an initial Glasgow Coma Scale score of 3 or 4. AB - OBJECT: Patients with traumatic brain injury (TBI) with low presenting Glasgow Coma Scale (GCS) scores have very high morbidity and mortality rates. Neurosurgeons may be faced with difficult decisions in managing the most severely injured (GCS scores of 3 or 4) patients. The situation may be considered hopeless, with little chance of a functional recovery. Long-term data are limited regarding the clinical outcome of children with severe head injury. The authors evaluate predictor variables and the clinical outcomes at discharge, 1 year, and long term (median 10.5 years) in a cohort of children with TBI presenting with postresuscitation GCS scores of 3 and 4. METHODS: A review of a prospectively collected trauma database was performed. Patients treated at Riley Hospital for Children (Indianapolis, Indiana) from 1988 to 2004 were reviewed. All children with initial GCS (modified for pediatric patients) scores of 3 or 4 were identified. Patients with a GCS score of 3 were compared with those with a GCS score of 4. The outcomes of all patients at the time of death or discharge and at 1-year and long-term follow-up were measured with a modified Glasgow Outcome Scale (GOS) that included a "normal" outcome. Long-term outcomes were evaluated by contacting surviving patients. Statistical "classification trees" were formed for survival and outcome, based on predictor variables. RESULTS: Sixty-seven patients with a GCS score of 3 or 4 were identified in a database of 1636 patients (4.1%). Three of the presenting factors differed between the GCS 3 patients (n = 44) and the GCS 4 patients (n = 23): presence of hypoxia, single seizure, and open basilar cisterns on CT scan. The clinical outcomes were statistically similar between the 2 groups. In total, 48 (71.6%) of 67 patients died, remained vegetative, or were severely disabled by 1 year. Eight patients (11.9%) were normal at 1 year. Ten of the 22 patients with long-term follow-up were either normal or had a GOS score of 5. Multiple clinical, historical, and radiological factors were analyzed for correlation with survival and clinical outcome. Classification trees were formed to stratify predictive factors. The pupillary response was the factor most predictive of both survival and outcome. Other factors that either positively or negatively correlated with survival included hypothermia, mechanism of injury (abuse), hypotension, major concurrent symptoms, and midline shift on CT scan. Other factors that either positively or negatively predicted long-term outcome included hypothermia, mechanism of injury, and the assessment of the fontanelle. CONCLUSIONS: In this cohort of 67 TBI patients with a presenting GCS score of 3 or 4, 56.6% died within 1 year. However, approximately 15% of patients had a good outcome at 10 or more years. Factors that correlated with survival and outcome included the pupillary response, hypothermia, and mechanism. The authors discuss factors that may help surgeons make critical decisions regarding their most serious pediatric trauma patients. PMID- 26140393 TI - Improvements in body composition, anthropometric measurements and lipid profile following discontinuation of clozapine. AB - BACKGROUND: Metabolic syndrome (obesity, glucose intolerance, insulin resistance and dyslipidaemia) is a well-known adverse effect of most antipsychotics. It is particularly common in patients treated with olanzapine and clozapine. Currently, the mechanisms underlying its development are not completely understood. CASE REPORT: We present a case of improved body composition (reduced amount of total body fat and visceral adipose tissue), anthropometric measurements (body weight, waist, abdominal and hip circumferences) and lipid profile in a 31-year-old man with schizophrenia following discontinuation of clozapine. During a combined treatment with clozapine, flupentixol and ziprasidone, a routine laboratory test revealed a severe dyslipidaemia (triglycerides > 1800 mg/dL; > 20.3 mmol/L), despite previous lipid-lowering therapy. This abnormality completely recovered after clozapine has been discontinued. CONCLUSIONS: Clozapine may cause severe, but reversible metabolic abnormalities, including obesity and hypertriglyceridaemia. Atypical antipsychotic-related lipid abnormalities may have a very rapid onset, occur in relatively young patients, with severe lipid derangements and have potential serious complications. This case confirms how important is to monitor metabolic parameters in patients taking antipsychotics. Discontinuation or switching to another antipsychotic medication may improve components of the metabolic syndrome. PMID- 26140394 TI - Clinical interpretation of residual uptake in 11C-methionine positron emission tomography after treatment of basal ganglia germ cell tumors: report of 3 cases. AB - Although (11)C-methionine (MET)-PET has been used to diagnose intracranial germ cell tumors (GCTs) arising in the basal ganglia, whether this imaging technique is useful in assessing treatment response and residual tumor is still unclear. The authors report 3 cases of basal ganglia GCTs in which the residual MET uptake at the end of treatment did not develop into a relapse, even without additional treatment. Case 1 is a 22-year-old man who had a second relapse of a left basal ganglia germinoma with diffuse dissemination on the walls of both of his lateral ventricles. MET-PET revealed high MET accumulation around tumors and their surroundings (maximum standardized uptake value [SUVmax] 3.3). After all treatments, MET-PET demonstrated mild tracer accumulation in both basal ganglia (SUVmax 2.2). Progression-free survival was 56 months from the second relapse without any further treatment. Case 2 is a 17-year-old boy with a left basal ganglia germinoma that showed increased MET uptake (SUVmax 4.2). After treatment, MET-PET revealed residual MET uptake (SUVmax 2.4) along the left posterior limb of the internal capsule. Progression-free survival was 52 months from the start of treatment. Case 3 is a 7-year-old boy with a left basal ganglia choriocarcinoma with increased tumor MET uptake (SUVmax 2.5). A minor enhanced mass remained on MRI after treatment with residual MET accumulation (SUVmax 1.4). Progression-free survival was 44 months. Treatment strategies based on MET uptake on PET should be carefully designed in patients with basal ganglia GCTs to avoid overtreatment and complications. PMID- 26140396 TI - Surgical treatment of basal cell carcinoma and squamous cell carcinoma. AB - Non melanoma skin cancers (NMSC) are the most common human neoplasms, encompassing basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but also cutaneous lymphomas, adnexal tumors, merckel cell carcinoma and other rare tumors. The incidence of BCC and SCC varies significantly among different populations, and the overall incidence of both tumors has increased over the last decades. Although generally associated with a favorable prognosis, recent evidence suggests that the mortality rates of SCC might have been underestimated up-to-date.1 According to Medicare data, NMSC is the fifth most expensive cancer for health care systems. This increased economic burden is not associated with the cost of treating an individual patient, but with the large number of affected patients and the recurrence rates.2 Therefore, the adequate management of the primary tumor with a complete excision becomes a priority not only for the patient but also for the public health systems. Multiple treatment modalities are currently usedin clinicalpractice for the treatment of NMSC. While surgical excision (SE) remains the gold standard of care, non-surgical techniques have gained appreciation due to lower morbidity and better cosmetic results. The optimal management of treatment includes a complete tumor clearance, preservation of the normal tissue function, and the best possible cosmetic outcome.3 Surgery with a predefined excision margin is the treatment of choice for most NMSCs, with Mohs micrographic surgery being recommended for tumors considered to be at a higher recurrence risk or those developing on cosmetically sensitive areas.4, 5 Therefore, the surgical approach of a NMSC consists with three different and equally important steps. First the preoperative clinical assessment of the tumor margins, which can be facilitated by the use of dermoscopy. Second, the definition of the surgical margins depending on the tumor subtype and its biological behavior. Finally, the surgical procedure must be designed based on the anatomic site and the patient's charachteristics. This preoperative assessment requires specific skills and might be performed by a physician, the dermatosurgeon, two collaborating specialists, namely a dermatologist and a surgeon. PMID- 26140397 TI - Update on the use of confocal microscopy in melanoma and non-melanoma skin cancer. AB - Reflectance confocal microscopy (RCM) is a new technique enabling the visualization of the skin at a quasi-histological resolution, allowing the identification of clues for the diagnosis of skin diseases. The aim of this analysis was to provide new insights into the role of RCM in the diagnosis of skin cancers. Data comes from the most recent literature, taking into account previous essential reported information in this field. The study eligibility criteria were: studies providing update information, focusing on RCM findings in melanoma and non-melanoma skin cancers (NMSC), without restrictions for age, sex, ethnicity. Duplicated studies and single case report were excluded from this study. A search concerning the role of RCM in melanoma and NMSC was performed on the Medline. RCM clues were analyzed for different skin cancers, in particular melanoma and NMSC, in association with clinical, dermoscopic and histopathologic findings. Diagnostic accuracy, sensibility and specificity of the technique were reviewed. Furthermore, some new findings have been described and recent applications have been discussed. The selection of articles was limited in order to provide an up-to-date revision. In conclusion, several RCM features were implemented for the diagnosis of melanoma and NMSC, leading to a confocal-based classification in most cases. PMID- 26140398 TI - Utilization of laser interstitial thermotherapy guided by real-time thermal MRI as an alternative to separation surgery in the management of spinal metastasis. AB - OBJECT: High-grade malignant spinal cord compression is commonly managed with a combination of surgery aimed at removing the epidural tumor, followed by spinal stereotactic radiosurgery (SSRS) aimed at local tumor control. The authors here introduce the use of spinal laser interstitial thermotherapy (SLITT) as an alternative to surgery prior to SSRS. METHODS: Patients with a high degree of epidural malignant compression due to radioresistant tumors were selected for study. Visual analog scale (VAS) scores for pain and quality of life were obtained before and within 30 and 60 days after treatment. A laser probe was percutaneously placed in the epidural space. Real-time thermal MRI was used to monitor tissue damage in the region of interest. All patients received postoperative SSRS. The maximum thickness of the epidural tumor was measured, and the degree of epidural spinal cord compression (ESCC) was scored in pre- and postprocedure MRI. RESULTS: In the 11 patients eligible for study, the mean VAS score for pain decreased from 6.18 in the preoperative period to 4.27 within 30 days and 2.8 within 60 days after the procedure. A similar VAS interrogating the percentage of quality of life demonstrated improvement from 60% preoperatively to 70% within both 30 and 60 days after treatment. Imaging follow-up 2 months after the procedure demonstrated a significant reduction in the mean thickness of the epidural tumor from 8.82 mm (95% CI 7.38-10.25) before treatment to 6.36 mm (95% CI 4.65-8.07) after SLITT and SSRS (p = 0.0001). The median preoperative ESCC Grade 2 was scored as 4, which was significantly higher than the score of 2 for Grade 1b (p = 0.04) on imaging follow-up 2 months after the procedure. CONCLUTIONS: The authors present the first report on an innovative minimally invasive alternative to surgery in the management of spinal metastasis. In their early experience, SLITT has provided local control with low morbidity and improvement in both pain and the quality of life of patients. PMID- 26140399 TI - Laser interstitial thermotherapy for epidural tumor decompression: is there a role? PMID- 26140400 TI - Factors affecting survival in 43 consecutive patients after surgery for spinal metastases from thyroid carcinoma. AB - OBJECT: Spinal metastases account for the majority of bone metastases from thyroid cancer. The objective of the current study was to analyze a series of consecutive patients undergoing spinal surgery for thyroid cancer metastases in order to identify factors that influence overall survival. METHODS: The authors retrospectively reviewed the records of all patients who underwent surgery for spinal metastases from thyroid cancer between 1993 and 2010 at the University of Texas MD Anderson Cancer Center. RESULTS: Forty-three patients met the study criteria. Median overall survival was 15.4 months (95% CI 2.8-27.9 months) based on the Kaplan-Meier method. The median follow-up duration for the 4 patients who were alive at the end of the study was 39.4 months (range 1.7-62.6 months). On the multivariate Cox analysis, progressive systemic disease at spine surgery and postoperative complications were associated with worse overall survival (HR 8.98 [95% CI 3.46-23.30], p < 0.001; and HR 2.86 [95% CI 1.30-6.31], p = 0.009, respectively). Additionally, preoperative neurological deficit was significantly associated with worse overall survival on the multivariate analysis (HR 3.01 [95% CI 1.34-6.79], p = 0.008). Conversely, preoperative embolization was significantly associated with improved overall survival on the multivariate analysis (HR 0.43 [95% CI 0.20-0.94], p = 0.04). Preoperative embolization and longer posterior construct length were significantly associated with fewer and greater complications, respectively, on the univariate analysis (OR 0.24 [95% CI 0.06-0.93] p = 0.04; and OR 1.24 [95% CI 1.02-1.52], p = 0.03), but not the multivariate analysis. CONCLUSIONS: Progressive systemic disease, postoperative complications, and preoperative neurological deficits were significantly associated with worse overall survival, while preoperative spinal embolization was associated with improved overall survival. These factors should be taken into consideration when considering such patients for surgery. Preoperative embolization and posterior construct length significantly influenced the incidence of postoperative complications only on the univariate analysis. PMID- 26140401 TI - Preoperative opioid strength may not affect outcomes of anterior cervical procedures: a post hoc analysis of 2 prospective, randomized trials. AB - OBJECT: The aim of this study is to evaluate the relationship between preoperative opioid strength and outcomes of anterior cervical decompressive surgery. METHODS: A retrospective cohort of 1004 patients enrolled in 1 of 2 investigational device exemption studies comparing cervical total disc arthroplasty (TDA) and anterior cervical discectomy and fusion (ACDF) for single level cervical disease causing radiculopathy or myelopathy was selected. At a preoperative visit, opioid use data, Neck Disability Index (NDI) scores, 36-Item Short-Form Health Survey (SF-36) scores, and numeric rating scale scores for neck and arm pain were collected. Patients were divided into strong (oxycodone/morphine/meperidine), weak (codeine/propoxyphene/hydrocodone), and opioid-naive groups. Preoperative and postoperative (24 months) outcomes scores were compared within and between groups using the paired t-test and ANCOVA, respectively. RESULTS: Patients were categorized as follows: 226 strong, 762 weak, and 16 opioid naive. The strong and weak groups were similar with respect to age, sex, race, marital status, education level, Worker's Compensation status, litigation status, and alcohol use. At 24-month follow-up, no differences in change in arm or neck pain scores (arm: strong -52.3, weak -50.6, naive -54.0, p = 0.244; neck: strong -52.7, weak -50.8, naive -44.6, p = 0.355); NDI scores (strong -36.0, weak -33.3, naive -32.3, p = 0.181); or SF-36 Physical Component Summary scores (strong: 14.1, weak 13.3, naive 21.7, p = 0.317) were present. Using a 15-point improvement in NDI to determine success, the authors found no between-groups difference in success rates (strong 80.6%, weak 82.7%, naive 73.3%, p = 0.134). No difference existed between treatment arms (TDA vs ACDF) for any outcome at any time point. CONCLUSIONS: Preoperative opioid strength did not adversely affect outcomes in this analysis. Careful patient selection can yield good results in this patient population. PMID- 26140403 TI - Gradual spinal cord decompression through migration of floated plaques after anterior decompression via a posterolateral approach for OPLL in the thoracic spine. AB - OBJECT: Several surgical procedures have been developed to treat thoracic OPLL (ossification of the posterior longitudinal ligament). However, favorable surgical results are not always achieved, and consistent protocols and procedures for surgical treatment of OPLL in this region have not been established. Beak type OPLL in the thoracic spine is known to be the most complicated form of OPLL to treat surgically. In this study, the authors examine the clinical outcomes after anterior decompression via a posterolateral approach for beak-type OPLL in the thoracic spine and address the gradual spinal cord decompression caused by migration of the floated plaques after surgery. METHODS: Between 2011 and 2013, a total of 12 patients with thoracic myelopathy due to OPLL were surgically treated at the authors' institute. The study group for this paper comprises 6 of those 12 patients. These 6 patients, who had beak-type OPLL, underwent with anterior decompression and instrumented fusion via the authors' posterolateral approach based surgical technique. The other 6 patients, who exhibited other types of OPLL, underwent posterior decompression and instrumented fusion. In the study group (the 6 patients with beak-type OPLL), half of the patients (the 3 patients who were treated first) were treated with removal of the ossified ligament. These patients are referred to as the removal group. The other 3 patients were treated by means of "floating" the OPLL plaques and are referred to as the floating group. Clinical and radiographic outcomes were evaluated in these 6 cases. RESULTS: The recovery rates were 52.4% in the removal group and 60.0% in the floating group. Two patients in the removal group had operative complications, including a dural tear and temporary neurological deterioration. No operative complications were encountered in the floating group. In all 3 cases in the floating group, floating of the ossified ligament was completely achieved, and the floated plaque gradually migrated into the ventral bone resection areas. The mean migration distances of the floated plaque were 2.4 mm, 4.3 mm, 4.7 mm, and 4.8 mm at 1, 3, 6, and 12 months after surgery. CONCLUSIONS: Treatment of beak type OPLL in the thoracic spine via the posterolateral approach-based floating plaque technique was safe and effective in this small case series. Gradual migration of the floated plaques provided additional spinal cord decompression during the postoperative course. PMID- 26140402 TI - Clinical and radiological outcomes of modified posterior closing wedge osteotomy for the treatment of posttraumatic thoracolumbar kyphosis. AB - OBJECT: Most thoracolumbar fractures have a good healing outcome with adequate treatment. However, posttraumatic thoracolumbar kyphosis can occur in a proportion of thoracolumbar fractures after inappropriate treatment, osteoporosis, or osteonecrosis of the vertebral body. There are several surgical options to correct posttraumatic thoracolumbar kyphosis, including anterior, posterior, and combined approaches, which are associated with varying degrees of success. The aim of this study was to assess the use of a modified closing wedge osteotomy for the treatment of posttraumatic thoracolumbar kyphosis and to evaluate the radiographic findings and clinical outcomes of patients treated using this technique. METHODS: Thirteen consecutive patients with symptomatic posttraumatic thoracolumbar kyphosis were treated using a modified closing wedge osteotomy. The mean patient age was 62 years. The kyphosis apex ranged from T-10 to L-2. The sagittal alignment, kyphotic angle, neurological function, visual analog scale for back pain, and Oswestry Disability Index were evaluated before surgery and at follow-up. RESULTS The mean preoperative regional angle was 27.4 degrees , and the mean correction angle was 29.6 degrees . Sagittal alignment improved with a mean correction rate of 58.3%. The mean surgical time was 275 minutes, and the mean intraoperative blood loss was 1585 ml. The intraoperative complications included 2 dural tears, 1 nerve root injury, and 1 superficial wound infection. The mean visual analog scale score for back pain improved from 6. 6 to 2, and the Oswestry Disability Index score decreased from 55.4 to 22.6 at the last follow-up. All patients achieved bony anterior fusion based on the presence of trabecular bone bridging at the osteotomy site. CONCLUTIONS: The modified posterior closing wedge osteotomy technique achieves satisfactory kyphosis correction with direct visualization of the circumferentially decompressed spinal cord, as well as good fusion with less blood loss and fewer complications. It is an alternative method for treating patients with posttraumatic thoracolumbar kyphosis. PMID- 26140404 TI - Impact of sagittal spinopelvic alignment on clinical outcomes after decompression surgery for lumbar spinal canal stenosis without coronal imbalance. AB - OBJECT: The object of this study was to investigate correlations between sagittal spinopelvic alignment and improvements in clinical and quality-of-life (QOL) outcomes after lumbar decompression surgery for lumbar spinal canal stenosis (LCS) without coronal imbalance. METHODS: The authors retrospectively reviewed data from consecutive patients treated for LCS with decompression surgery in the period from 2009 through 2011. They examined correlations between preoperative or postoperative sagittal vertical axis (SVA) and radiological parameters, clinical outcomes, and health-related (HR)QOL scores in patients divided according to SVA. Clinical outcomes were assessed according to Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) scores. Health-related QOL was evaluated using the Roland-Morris Disability Questionnaire (RMDQ) and the JOA Back Pain Evaluation Questionnaire (JOABPEQ). RESULTS: One hundred nine patients were eligible for inclusion in the study. Compared to patients with normal sagittal alignment prior to surgery (Group A: SVA < 50 mm), those with preoperative sagittal imbalance (Group B: SVA >= 50 mm) had significantly smaller lumbar lordosis and thoracic kyphosis angles and larger pelvic tilt. In Group B, there was a significant decrease in postoperative SVA compared with the preoperative SVA (76.3 +/- 29.7 mm vs. 54.3 +/- 39.8 mm, p = 0.004). The patients in Group B with severe preoperative sagittal imbalance (SVA > 80 mm) had residual sagittal imbalance after surgery (82.8 +/- 41.6 mm). There were no significant differences in clinical and HRQOL outcomes between Groups A and B. Compared to patients with normal postoperative SVA (Group C: SVA < 50 mm), patients with a postoperative SVA >= 50 mm (Group D) had significantly lower JOABPEQ scores, both preoperative and postoperative, for walking ability (preop: 36.6 +/- 26.3 vs. 22.7 +/- 26.0, p = 0.038, respectively; postop: 71.1 +/- 30.4 vs. 42.5 +/- 29.6, p < 0.001) and social functioning (preop: 38.7 +/- 18.5 vs. 30.2 +/- 16.7, p = 0.045; postop: 67.0 +/- 25.8 vs. 49.6 +/- 20.0, p = 0.001), as well as significantly higher postoperative RMDQ (4.9 +/- 5.2 vs. 7.9 +/- 5.7, p = 0.015) and VAS scores for low-back pain (2.68 +/- 2.69 vs. 3.94 +/- 2.59, p = 0.039). CONCLUSIONS: Preoperative sagittal balance was not significantly correlated with clinical or HRQOL outcomes after decompression surgery in LCS patients without coronal imbalance. Decompression surgery improved the SVA value in patients with preoperative sagittal imbalance; however, the patients with severe preoperative sagittal imbalance (SVA > 80 mm) had residual imbalance after decompression surgery. Both clinical and HRQOL outcomes were negatively affected by postoperative residual sagittal imbalance. PMID- 26140405 TI - Clinical analysis of spinal stereotactic radiosurgery in the treatment of neurogenic tumors. AB - OBJECT: In this study the authors sought to evaluate clinical outcomes after using stereotactic radiosurgery (SRS) to treat benign and malignant spinal neurogenic tumors. METHODS: The authors reviewed a total of 66 procedures of spinal SRS performed between 2001 and 2013 for 110 tumors in 58 patients with spinal neurogenic tumors, which included schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNSTs). The clinical and radiological findings were evaluated in patients with benign neurogenic tumors. For the 4 patients with MPNSTs, the authors reported overall survival and results of additional immunohistochemical staining to predict the survival difference among the patients. RESULTS: Of the 92 benign neurogenic tumors, 65 tumors that were serially followed up using MRI after SRS showed significant change in mean tumor volume, from a mean of 12.0 +/- 2.6 cm3 pre-SRS to 10.8 +/- 2.5 cm3 post-SRS (p = 0.027), over an average of 44 months. The local control rate of benign neurogenic tumors was 95.4%. The 34 patients who presented with clinical symptoms of pain showed a significant symptomatic improvement. The initial mean visual analog scale (VAS) score was 6.0 and decreased dramatically to 1.0 after SRS during an average follow-up period of 10.9 months (median of 8.1 months). Although the proportions of transient swelling and loss of intramural enhancement were significantly different among the groups, there was no statistically significant correlation between those 2 factors and local tumor control (p = 0.253 and 0.067, respectively; Fisher's exact text). Cross-table analysis also indicated that there was no statistically significant relationship between groups with loss of intramural enhancement and transient swelling. The median survival of neurofibromatosis Type 1 (NF1)-related and sporadic MPNSTs was 1.13 and 5.8 years, respectively. Immunohistochemical results showed that S100 was expressed in a sporadic MPNST or neurofibroma, whereas topoisomerase-IIa was expressed in NF1-related MPNSTs. CONCLUSIONS: SRS is an effective treatment modality for benign neurogenic tumors, while MPNSTs showed heterogeneity in their responses to SRS. PMID- 26140406 TI - Predictive value of 3-month lumbar discectomy outcomes in the NeuroPoint-SD Registry. AB - OBJECT: The authors have established a multicenter registry to assess the efficacy and costs of common lumbar spinal procedures using prospectively collected outcomes. Collection of these data requires an extensive commitment of resources from each site. The aim of this study was to determine whether outcomes data from shorter-interval follow-up could be used to accurately estimate long term outcome following lumbar discectomy. METHODS: An observational prospective cohort study was completed at 13 academic and community sites. Patients undergoing single-level lumbar discectomy for treatment of disc herniation were included. SF-36 and Oswestry Disability Index (ODI) data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Quality-adjusted life year (QALY) data were calculated using SF-6D utility scores. Correlations among outcomes at each follow-up time point were tested using the Spearman rank correlation test. RESULTS: One hundred forty-eight patients were enrolled over 1 year. Their mean age was 46 years (49% female). Eleven patients (7.4%) required a reoperation by 1 year postoperatively. The overall 1-year follow-up rate was 80.4%. Lumbar discectomy was associated with significant improvements in ODI and SF-36 scores (p < 0.0001) and with a gain of 0.246 QALYs over the 1-year study period. The greatest gain occurred between baseline and 3-month follow-up and was significantly greater than improvements obtained between 3 and 6 months or 6 months and 1 year(p < 0.001). Correlations between 3-month, 6-month, and 1-year outcomes were similar, suggesting that 3-month data may be used to accurately estimate 1-year outcomes for patients who do not require a reoperation. Patients who underwent reoperation had worse outcomes scores and nonsignificant correlations at all time points. CONCLUSIONS: This national spine registry demonstrated successful collection of high-quality outcomes data for spinal procedures in actual practice. Three-month outcome data may be used to accurately estimate outcome at future time points and may lower costs associated with registry data collection. This registry effort provides a practical foundation for the acquisition of outcome data following lumbar discectomy. PMID- 26140407 TI - Myelopathy-mimicking symptoms of epidural venous engorgement and syringomyelia due to inferior vena cava stenosis at the thoracolumbar junction in a patient with Budd-Chiari syndrome. AB - Epidural venous engorgement can result from various lesions, such as arteriovenous malformation, thrombosis or occlusion of the inferior vena cava (IVC), or an abdominal masslike lesion. Most patients with these problems complain of low-back pain, radicular pain, or neurogenic claudication, which are symptoms suggestive of disc herniation or spinal stenosis. However, these patients rarely exhibit neurological deficits or cauda equina syndrome. The authors encountered a case of a 60-year-old man presenting with lower-extremity weakness and voiding difficulty for a period of 1 year. To investigate the patient's myelopathy-mimicking symptoms, a lumbar spine MRI scan was performed. The MR images exhibited tortuous and dilated spinal vessels compressing the spinal cord and thecal sac at the T11-L3 level, which were concurrent with syringomyelia evidenced by a 22 * 2.5-mm cyst at the T11-12 level. 3D CT scanning of the whole aorta revealed total occlusion and regression of the IVC in the intrahepatic region 3 cm inferior to the right atrium and dilation of multiple collateral veins. The patient was diagnosed with chronic Budd-Chiari syndrome Type I. The authors performed venography, followed by intrahepatic IVC recanalization via stent placement under fluoroscopic and ultra sonographic guidance and without surgical exploration. After this treatment, there was a marked decrease in epidural venous engorgement and the patient's symptoms resolved almost completely. This case indicates that epidural venous engorgement at thoracolumbar levels may cause symptoms suggestive of myelopathy and can be successfully treated by minimally invasive procedures to eliminate the underlying causes. PMID- 26140409 TI - Polymethoxyflavones Isolated from the Peel of Miaray Mandarin (Citrus miaray) Have Biofilm Inhibitory Activity in Vibrio harveyi. AB - Citrus fruits are a good source of bioactive compounds with numerous beneficial biological activities. In the present study, fruits of the unexplored Miaray mandarin were used for the isolation of 10 bioactive compounds. Dried peels were sequentially extracted with hexane and chloroform in a Soxhlet-type apparatus for 8 h. The extracts were concentrated under vacuum and separated by flash chromatography to obtain nine polymethoxyflavones and a limonoid. The purity of each compound was analyzed by high-performance liquid chromatography (HPLC), and the compounds were identified by spectral analysis using MALDI-TOF-MS and NMR. The isolated compounds were identified as 5-hydroxy-3,7,3',4' tetramethoxyflavone, 5,6,7,8,4'-pentamethoxyflavone (tangeretin), 3,5,6,7,8,3',4' heptamethoxyflavone, 5,6,7,8,3',4'-hexamethoxyflavone (nobiletin), 3,5,7,8,3',4' hexamethoxyflavone, 3,5,7,3',4'-pentamethoxyflavone (pentamethylquercetin), 5,7,4'-trimethoxyflavone, 5,7,8,4'-tetramethoxyflavone, 5,7,8,3',4' pentamethoxyflavone, and limonin. These compounds were further tested for their ability to inhibit cell-cell signaling and biofilm formation in Vibrio harveyi. Among the evaluated polymethoxyflavones, 3,5,6,7,8,3',4'-heptamethoxyflavone and 3,5,7,8,3',4'-hexamethoxyflavone inhibited autoinducer-mediated cell-cell signaling and biofilm formation. These results suggest that Miaray mandarin fruits are a good source of polymethoxyflavones. This is the first report on the isolation of bioactive compounds from Miaray mandarin and evaluation of their biofilm inhibitory activity as well as isolation of pentamethylquercetin from the Citrus genus. PMID- 26140410 TI - Efficient Delivery of DOX to Nuclei of Hepatic Carcinoma Cells in the Subcutaneous Tumor Model Using pH-Sensitive Pullulan-DOX Conjugates. AB - A series of pullulan-doxorubicin conjugates (Pu-DOXs) were investigated for effectively delivering DOX to nuclei of hepatic carcinoma cells in subcutaneous tumor model. These Pu-DOXs were prepared by conjugating DOX onto pullulan molecule via pH-responsive hydrazone bond using spacers with different alkane chain length. The highest drug loading content of Pu-DOXs went up to nearly 50%, and the diameter of Pu-DOX nanoparticles ranged from 50 to 170 nm, as measured by DLS and TEM. These Pu-DOX nanoparticles could rapidly release DOX in the acidic environment at pH = 5.0 while being kept relatively stable in neural conditions. The in vitro cell coculture experiments revealed that these Pu-DOX nanoparticles were selectively internalized by hepatic carcinoma cells through receptor mediated endocytosis via asialoglycoprotein receptor on the hepatic carcinoma cell surface. DOX was rapidly released from Pu-DOX nanoparticles in acidic endosome/lysosome, diffused into cell nuclei due to its strong affinity to nucleic acid, inhibited the cell proliferation, and accelerated the cell apoptosis. In the nude mice subcutaneous hepatic carcinoma model, Pu-DOX nanoparticles efficiently accumulated in the tumor site through the enhanced permeation and retention effect. Then DOX was specifically internalized by hepatic carcinoma cells and rapidly diffused into the nuclei of cells. Compared with the control group in in vivo experiments, these Pu-DOX nanoparticles effectively inhibited solid tumor growth, prolonging the lifetime of the experimental animal. These pH sensitive nanoparticles might provide an important clinical implication for targeted hepatic carcinoma therapy with high efficiency and low systematic toxicity. PMID- 26140411 TI - Diffusion of Small Solute Particles in Viscous Liquids: Cage Diffusion, a Result of Decoupling of Solute-Solvent Dynamics, Leads to Amplification of Solute Diffusion. AB - We study the diffusion of small solute particles through solvent by keeping the solute-solvent interaction repulsive and varying the solvent properties. The study involves computer simulations, development of a new model to describe diffusion of small solutes in a solvent, and also mode coupling theory (MCT) calculations. In a viscous solvent, a small solute diffuses via coupling to the solvent hydrodynamic modes and also through the transient cages formed by the solvent. The model developed can estimate the independent contributions from these two different channels of diffusion. Although the solute diffusion in all the systems shows an amplification, the degree of it increases with solvent viscosity. The model correctly predicts that when the solvent viscosity is high, the solute primarily diffuses by exploiting the solvent cages. In such a scenario the MCT diffusion performed for a static solvent provides a correct estimation of the cage diffusion. PMID- 26140412 TI - Characterization and Analysis of Liquid Waste from Marcellus Shale Gas Development. AB - Hydraulic fracturing of shale for gas production in Pennsylvania generates large quantities of wastewater, the composition of which has been inadequately characterized. We compiled a unique data set from state-required wastewater generator reports filed in 2009-2011. The resulting data set, comprising 160 samples of flowback, produced water, and drilling wastes, analyzed for 84 different chemicals, is the most comprehensive available to date for Marcellus Shale wastewater. We analyzed the data set using the Kaplan-Meier method to deal with the high prevalence of nondetects for some analytes, and compared wastewater characteristics with permitted effluent limits and ambient monitoring limits and capacity. Major-ion concentrations suggested that most wastewater samples originated from dilution of brines, although some of our samples were more concentrated than any Marcellus brines previously reported. One problematic aspect of this wastewater was the very high concentrations of soluble constituents such as chloride, which are poorly removed by wastewater treatment plants; the vast majority of samples exceeded relevant water quality thresholds, generally by 2-3 orders of magnitude. We also examine the capacity of regional regulatory monitoring to assess and control these risks. PMID- 26140413 TI - Functionalized Polymer Microgel Particles Enable Customizable Production of Label Free Sensor Arrays. AB - Probe molecule immobilization onto surfaces is a critical step in the production of many analytical devices, including labeled and label-free microarrays. New methods to increase the density and uniformity of probe deposition have the potential to significantly enhance the ultimate limits of detection and reproducibility. Hydrogel-based materials have been employed in the past to provide a 3D protein-friendly surface for deposition of antibodies and nucleic acids. However, these methods are susceptible to variation during polymerization of the hydrogel scaffold and provide limited opportunities for tuning deposition parameters on an antibody-by-antibody basis. In this work, a versatile hydrogel nanoparticle deposition method was developed for the production of label-free microarrays and tested in the context of antibody-antigen binding. Poly(N isopropylacrylamide) nanoparticles (PNIPAM) were conjugated to antibodies using an avidin/biotin system and deposited onto surfaces using a noncontact printing system. After drying, these gel spots formed uniform and thin layers <10 nm in height. The conjugates were characterized with dynamic light scattering, scanning electron microscopy, and atomic force microscopy. We tested this format in the context of tumor necrosis factor-alpha (TNF-alpha) detection via arrayed imaging reflectometry (AIR), a label-free protein microarray method. This method of probe molecule deposition should be generally useful in the production of microarrays for label-free detection. PMID- 26140414 TI - Effects of a weight loss program on body composition and the metabolic profile in obese postmenopausal women displaying various obesity phenotypes: a MONET group study. AB - Obesity is a heterogeneous condition, since the metabolic profile may differ greatly from one individual to another. The objective of this study was to compare the effect of a 6-month diet-induced weight loss program on body composition and the metabolic profile in obese individuals displaying different obesity phenotypes. Secondary analyses were done on 129 obese (% body fat: 46% +/ 4%) postmenopausal women (age: 57 +/- 4 years). Outcome measures included body composition, body fat distribution, glucose homeostasis, fasting lipids, and blood pressure. Obesity phenotypes were determined based on lean body mass (LBM) index (LBMI = LBM/height(2)) and visceral fat (VF) accumulation, as follows: 1, lower VF and lower LBMI (n = 35); 2, lower VF and higher LBMI (n = 19); 3, higher VF and lower LBMI (n = 14); and 4, higher VF and higher LBMI (n = 61). All groups had significantly improved measures of body composition after the intervention (P < 0.0001). Greater decreases in LBM and LBMI were observed in the higher LBMI groups than in the lower LBMI groups (P < 0.0001). Similarly, decreases in VF were greater in the higher VF groups than in the lower VF groups (P < 0.05). Overall, fasting insulin levels and glucose disposal improved following the intervention, with higher LBMI groups showing a trend for greater improvements (P = 0.06 and 0.07, respectively). Overall, no difference was observed among the different obesity phenotypes regarding improvements in the metabolic profile in response to weight loss. Individuals displaying higher VF or higher LBMI at baseline experienced significantly greater decreases for these variables after the intervention. PMID- 26140415 TI - Consumption of acai (Euterpe oleracea Mart.) functional beverage reduces muscle stress and improves effort tolerance in elite athletes: a randomized controlled intervention study. AB - The study analyzed the effect of an acai (Euterpe oleracea Mart.) functional beverage (AB) on muscle and oxidative stress markers, cardiorespiratory responses, perceived exertion, and time-to-exhaustion during maximal treadmill running. The beverage was developed as an ergogenic aid for athletes and contained 27.6 mg of anthocyanins per dose. Fourteen athletes performed 3 exercise tests: a ramp-incremental maximal exercise test and 2 maximal exercise bouts performed in 2 conditions (AB and without AB (control)) at 90% maximal oxygen uptake. Blood was collected at baseline and after maximal exercise in both conditions to determine biomarkers. AB increased time to exhaustion during short term high-intensity exercise (mean difference: 69 s, 95% confidence interval = 296 s to 159 s, t = 2.2, p = 0.045), attenuating the metabolic stress induced by exercise (p < 0.05). AB also reduced perceived exertion and enhanced cardiorespiratory responses (p < 0.05). The AB may be a useful and practical ergogenic aid to enhance performance during high-intensity training. PMID- 26140416 TI - Associations between heart rate variability, metabolic syndrome risk factors, and insulin resistance. AB - The purpose of this study was to examine differences in heart rate variability (HRV) in metabolic syndrome (MetS) and to determine associations between HRV parameters, MetS risk factors, and insulin resistance (homeostasis model assessment for insulin resistance (HOMA-IR)). Participants (n = 220; aged 23-70 years) were assessed for MetS risk factors (waist circumference, blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol) and 5-min supine HRV (time and frequency domain and nonlinear). HRV was compared between those with 3 or more (MetS+) and those with 2 or fewer MetS risk factors (MetS-). Multiple linear regression models were built for each HRV parameter to investigate associations with MetS risk factors and HOMA-IR. Data with normal distribution are presented as means +/- SD and those without as median [interquartile range]. In women, standard deviation of R-R intervals 38.0 [27.0] ms, 44.5 [29.3] ms; p = 0.020), low-frequency power (5.73 +/- 1.06 ln ms(2), 6.13 +/- 1.05 ln ms(2); p = 0.022), and the standard deviation of the length of the Poincare plot (46.8 [31.6] ms, 58.4 [29.9] ms; p = 0.014) were lower and heart rate was higher (68 [13] beats/min, 64 [12] beats/min; p = 0. 018) in MetS+ compared with MetS-, with no differences in men. Waist circumference was most commonly associated with HRV, especially frequency domain parameters. HOMA-IR was associated with heart rate. In conclusion, MetS+ women had a less favourable HRV profile than MetS- women, but there were no differences in men. HOMA-IR was associated with heart rate, not HRV. PMID- 26140417 TI - Food group preferences and energy balance in moderately obese postmenopausal women subjected to brisk walking program. AB - The objective of the study was to examine the effects of a 16-week walking program on food group preferences and energy balance of sedentary, moderately obese (body mass index, 29-35 kg/m(2)), postmenopausal Caucasian women, aged 60 +/- 5 years old. One hundred and fifty-six volunteers were subjected to 3 sessions/week of 45 min of walking at 60% of heart rate reserve. Total energy intake (TEI) and food group preferences (3-day dietary record), total energy expenditure (TEE, 3-day physical activity diary), cardiorespiratory fitness (2-km walking test), anthropometry, and body composition (bioelectrical impedance) were measured before and after walking. Data were statistically analyzed using an ANOVA with repeated measures on 1 factor (time). The modest increase in TEE of 151 +/- 24 kcal/day (p < 0.0001) leads to body weight, fat mass losses, and waist girth reduction (p < 0.0001). TEI remained unchanged despite a slight decrease in carbohydrate intake and a minor increase in protein intake (p < 0.05). Analysis of food records revealed a decreased consumption of fruits (p < 0.05) and sweet and fatty foods (p < 0.01), but an increase in oil consumption (p < 0.0001) after walking. Women with the highest body weight loss showed the greatest reduction in the consumption of fruits, sugar, sweet foods, and fatty foods (p < 0.05). Women with the greatest fat mass loss showed the highest decrease in fatty food intake (p < 0.05). In conclusion, although our walking program changed some food group consumption patterns, body weight loss was primarily because of the increased TEE. PMID- 26140419 TI - Radiosurgery for Spinal Intramedullary Arteriovenous Malformations: A Literature Review. AB - INTRODUCTION: Intramedullary spinal cord arteriovenous malformations (SCAVMs) comprise only 3 to 4% of spinal cord pathologies and are often not amenable to total resection due to extensive involvement with spinal cord parenchyma and multiple arterial feeding vessels. METHODS: A electronic database search from 1966 to February 28, 2014, was conducted for relevant articles using the keywords and Medical Subject Headings strings spinal arteriovenous malformation, spinal radiosurgery, spinal vascular malformation, and radiosurgery for vascular lesions. Target outcomes measures were nidus obliteration, neurologic improvement, and complication rate. RESULTS: Four retrospective articles containing a total of 30 patients were identified that described patients with SCAVMs presenting with symptomatic intramedullary or subarachnoid hemorrhage. Eighteen patients underwent treatment with CyberKnife with dosages ranging from 21 to 40 Gy (or a maximum biological equivalent dose of 58 Gy for early treatment effect) (Accuray, Inc., Sunnyvale, California, United States), 10 with a linear accelerator and real-time respiratory tracking ranging from 32 to 40 Gy, and 2 patients with external-beam radiotherapy receiving 45 Gy and 50 Gy, respectively. The mean time for clinical follow-up was 43.5 months (range: 27.9-60 months). There were no cases of spinal cord hemorrhage after radiosurgery. Nor were there any cases of neurologic worsening or signs and symptoms of neuropathic pain or myelitis. A total of 29 of the 30 patients obtained follow-up. PMID- 26140418 TI - Intraoperative Micro-Doppler in Cerebral Arteriovenous Malformations. AB - INTRODUCTION: Intraoperative micro-Doppler (IOMD), intraoperative digital substraction angiography (DSA), and microscope-integrated indocyanine green angiography are methods that guide neurosurgical resection of arteriovenous malformations (AVMs) in the brain and minimize the trauma of healthy tissue. In this study we emphasize the use of IOMD in AVM surgery, analyzing the advantages and the limitations of this method. Patients and METHODS: A total of 32 patients were diagnosed with an AVM. Supplying arteries and draining veins were analyzed regarding hemodynamic profiles, flow velocities, pulsatility index (PI), and resistance index (RI). Venous drainages were accompanied by arterial blood flow disturbances that showed typical characteristics in all cases. We set an angle of 60 degrees between the examined vessel and the probe to achieve a more reliable and comparable measurement. Postoperative DSA was performed in all patients. RESULTS: Supplying arterial blood vessels of AVMs could be identified by their characteristic blood flow profiles with PI < 0.7 and RI < 0.55. Drainage veins in all 32 cases showed normalized venous flow patterns without arterial flow turbulences at the end of the surgical procedure. Postoperative DSA revealed a residual AVM in one patient. CONCLUSIONS: IOMD constitutes a safe, accurate, and low-cost imaging modality for evaluating blood flow velocities and for optimal stepwise AVM elimination without unnecessary sacrifice of veins. PI and RI are reliable parameters in diagnosing cerebrovascular malformations, but systolic and diastolic flow velocities may vary to a greater extent. This phenomenon has never been elucidated previously and therefore needs to be emphasized when using this technique intraoperatively. PMID- 26140420 TI - Catheter-Based Trans-Epidural Approach to Aspirate Cervical and Thoracic Epidural Abscesses: A Cadaveric Feasibility Study. AB - BACKGROUND: Approaching and aspirating cervical and high thoracic epidural abscesses through a trans-epidural route from the lumbar region access represents an alternative method for selected patients. OBJECTIVE: We determined the feasibility of catheter-based manipulation and aspiration using the trans epidural route. MATERIAL AND METHODS: A custom designed infusion-suction catheter system that includes an outer suction catheter and inner infusion catheter in concentric relation with radio-opaque marker bands was tested in a cadaveric preparation to determine (1) the ability to place an aspiration catheter over a guidewire using a percutaneous approach within the posterior lumbar epidural space; (2) the highest vertebral level a catheter can be advanced within the epidural space; and (3) the ability to aspirate artificial purulent-like material placed in the cervical and thoracic level epidural space. RESULTS: We were able to advance two infusion-suction catheter systems from a 14G Touhy spinal needle inserted via an oblique parasagittal approach at the L2-L3 intervertebral space. The infusion-suction catheter was advanced up to the level of the cervical vertebral level of C2 within the epidural space under fluoroscopic guidance. We were able to aspirate artificial purulent-like material directly injected with a 22G Quincke spinal needle at vertebral levels C4-C5 and at vertebral levels T10 T11 by aspiration and manipulation of the outer catheter within the epidural space at levels C3-C7 and T9-L1, respectively. CONCLUSIONS: Our observations support the further exploration of a percutaneous catheter-based trans-epidural approach to treat epidural abscesses. The trans-epidural approach may be used alone or as a staged or concurrent approach with open surgical treatment. PMID- 26140421 TI - Avoiding Complications in Endoscopic Third Ventriculostomy. AB - Endoscopic neurosurgical techniques hold the potential for reducing morbidity. But they are also associated with limitations such as the initial learning curve, proximal blind spot, visual obscurity, difficulty in controlling bleeding, disorientation, and loss of stereoscopic image. Although some of the surgical techniques in neuroendoscopy and microsurgery are similar, endoscopy requires additional skills. A thorough understanding of endoscopic techniques and their limitations is required to get maximal benefit. Knowledge of possible complications and techniques to avoid such complications can improve results in endoscopic third ventriculostomy (ETV). The surgeon must be able to manage complications and have a second strategy such as a cerebrospinal fluid shunt if ETV fails. It is better to abandon the procedure if there is disorientation or a higher risk of complications such as bleeding or a thick and opaque floor without any clear visualization of anatomy. Attending live workshops, practice on models and simulators, simpler case selection in the initial learning curve, and hands on cadaveric workshops can reduce complications. Proper case selection, good surgical technique, and better postoperative care are essential for a good outcome in ETV. Although it is difficult to make a preoperative diagnosis of complex hydrocephalus (combination of communicating and obstructive), improving methods to detect the exact type of hydrocephalus before surgery could increase the success rate of ETV and avoid an unnecessary ETV procedure in such cases. PMID- 26140422 TI - Mental Health Care Delivered to Younger and Older Adults by Office-Based Physicians Nationally. AB - OBJECTIVES: To compare the provision of mental health care to older adults with that provided to younger adults. DESIGN: Analysis of the National Ambulatory Medical Care Survey. SETTING: Visits to office-based physicians in the United States, 2007 to 2010 (n = 100,661 visits). PARTICIPANTS: Individuals with an outpatient visit resulting in a mental health diagnosis or treatment, defined as a visit resulting in a mental disorder diagnosis, at which a psychotropic medication was prescribed, to a psychiatrist, or including psychotherapy. MEASUREMENTS: The number of each type of mental healthcare visit was estimated according to participant age (21 to 64, >=65), along with the percentage this represented of all office-based care and the annual visit rate per 100 population. Within each visit type, age groups were compared according to clinical and demographic characteristics such as sex, diagnosed mental illness, and use of psychotropic agents. RESULTS: Older adults had a smaller proportion than younger adults of visits with a mental disorder diagnosis (4.8% vs 9.5%, chi square = 228.21, P < .001), to a psychiatrist (0.9% vs 4.0%, chi-square = 233.76, P < .001), and including psychotherapy (0.6% vs 2.3%, chi-square = 57.65, P < .001). The percentage of older adult psychotropic visits was slightly smaller than of younger adult visits (18.1% vs 19.2%, chi-square = 5.33, P = .02). Older adults had a higher rate of psychotropic visits (121.4 per 100 population) than younger adults (56.8 per 100 population). CONCLUSION: Less care of older adults is from psychiatrists or incorporates psychotherapy. Older adults have a far higher rate of psychotropic use than younger adults on a per-population basis. Addressing the mental healthcare needs of older adults will require care in nonspecialty settings. PMID- 26140423 TI - Greater Occipital Nerve Blockade: A Safe and Effective Option for the Acute Treatment of Hemiplegic Aura. AB - BACKGROUND: Prolonged auras such as those of hemiplegic migraine or migraine with brainstem aura may be extremely disabling. The availability of effective treatments is limited, but two case reports described cessation of the aura symptoms after a greater occipital nerve (GON) blockade. CASE: A 26-year-old woman with a history of hemiplegic migraine with prolonged auras came to our office with an episode of motor and sensory aura 1 hour after onset. Both muscle strength and sensory function started to improve immediately after a GON anesthetic blockade, and the patient was fully relieved in 50 minutes. CONCLUSION: GON blockade may be an effective option for the acute treatment of hemiplegic aura or other prolonged migraine auras. PMID- 26140424 TI - Retinal haemorrhages in a child struck by a barbell. PMID- 26140426 TI - Computerized working memory training has positive long-term effect in very low birthweight preschool children. AB - AIM: Working memory deficits are frequently found in children born preterm and have been linked to learning disabilities, and cognitive and behavioural problems. Our aim was to evaluate if a computerized working memory training program has long-term positive effects on memory, learning, and behaviour in very low-birthweight (VLBW) children at age 5 to 6 years. METHOD: This prospective, intervention study included 20 VLBW preschool children in the intervention group and 17 age-matched, non-training VLBW children in the comparison group. The intervention group trained with the Cogmed JM working memory training program daily for 5 weeks (25 training sessions). Extensive neuropsychological assessment and parental questionnaires were performed 4 weeks after intervention and at follow-up 7 months later. For most of the statistical analyses, general linear models were applied. RESULTS: At follow-up, higher scores and increased or equal performance gain were found in the intervention group than the comparison group on memory for faces (p=0.012), narrative memory (p=0.002), and spatial span (p=0.003). No group differences in performance gain were found for attention and behaviour. INTERPRETATION: Computerized working memory training seems to have positive and persisting effects on working memory, and visual and verbal learning, at 7-month follow-up in VLBW preschool children. We speculate that such training is beneficial by improving the ability to learn from the teaching at school and for further cognitive development. PMID- 26140427 TI - Enantioselective inhibition of d-serine transport by (S)-ketamine. AB - BACKGROUND AND PURPOSE: Patients with major depressive disorder receiving racemic ketamine, (R,S)-ketamine, experience transient increases in Clinician Administered Dissociative States Scale scores and a coincident drop in plasma d serine levels. The results suggest that (R,S)-ketamine produces an immediate, concentration-dependent pharmacological effect on d-serine plasma concentrations. One potential source of this effect is (R,S)-ketamine-induced inhibition of the transporter ASCT2, which regulates intracellular d-serine concentrations. In this study, we tested this hypothesis by examining the effect of (S)- and (R)-ketamine on ASCT2-mediated transport of d-serine in PC-12 and 1321N1 cells and primary neuronal cells in culture. EXPERIMENTAL APPROACH: Intracellular and extracellular d-serine levels were determined using capillary electrophoresis-laser-induced fluorescence and liquid chromatography-mass spectrometry respectively. Expression of ASCT2, Asc-1 and serine racemase was determined utilizing Western blotting. KEY RESULTS: (S)-Ketamine produced a concentration-dependent increase in intracellular d-serine and reduced extracellular d-serine accumulation. In contrast, (R)-ketamine decreased both intracellular and extracellular d-serine levels. The ASCT2 inhibitor, benzyl-d-serine (BDS), and ASCT2 gene knockdown mimicked the action of (S)-ketamine on d-serine in PC-12 cells, while the Asc-1 agonist d-isoleucine reduced intracellular d-serine and increased extracellular d serine accumulation. This response to d-isoleucine was not affected by BDS or (S) ketamine. Primary cultures of rat neuronal cells expressed ASCT2 and were responsive to (S)-ketamine and BDS. (S)- and (R)-ketamine increased the expression of monomeric serine racemase in all the cells studied, with (S) ketamine having the greatest effect. CONCLUSIONS AND IMPLICATIONS: (S)-Ketamine decreased cellular export of d-serine via selective inhibition of ASCT2, and this could represent a possible source of dissociative effects observed with (R,S) ketamine. PMID- 26140428 TI - Targeting Household Air Pollution for Curbing the Cardiovascular Disease Burden: A Health Priority in Sub-Saharan Africa. AB - Household air pollution (HAP) is a major public health problem, particularly in sub-Saharan Africa where most of the populations still rely on solid fuels for cooking, heating, and lighting. This narrative review highlights the direct and indirect evidence of the important role of HAP in cardiovascular disease, especially in sub-Saharan African countries where highest rates of major cardiovascular disease and death are observed, and thus provides ample reason for promotion of preventive interventions to reduce HAP exposures in the region. There is an urgent need for efficient strategies to educate populations on the health issues associated with this health hazard, to provide affordable clean cooking energy for poor people and to promote improved household ventilation. High-quality data on household energy practices and patterns of HAP and related health issues are still needed for efficient policy making in this region. PMID- 26140429 TI - The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies. PMID- 26140430 TI - Familial chronic lymphocytic leukemia in two siblings with ATM/13q14 deletion and a similar pattern of clonal evolution. PMID- 26140431 TI - Fanconi anemia gene variants in therapy-related myeloid neoplasms. PMID- 26140432 TI - Comparison of chemiluminescent immunoassay and ELISA for measles IgG and IgM. AB - In the context of measles elimination, the identification of recent infections is important for clinical laboratories. Serological diagnosis is achieved by detecting specific IgG and IgM. Recently an automated chemiluminescent immunoassay (CLIA) (Liaison, DiaSorin, Italy) has been used to quantify the measles antibody. The aim of this study was to compare this assay with Enzygnost ELISA (Siemens, Germany), with final classification of discrepancies by indirect immunofluorescence (Euroimmun, Germany). For measles IgM, 204 sera were analyzed: 50 IgM-positive, 104 IgM-negative/IgG-positive, and 50 from other viral infections (B19V, rubella, mumps, CMV, and EBV). For the measles IgG assay, 162 samples were tested: 106 were positive and 56 were negative. For measles IgM, the sensitivity and specificity of CLIA against ELISA were 94% (95% CI: 83.2-98.6) and 100% (95% CI: 97.1-100), respectively; the corrected figures after the final classification of discrepancies were 100% (95% CI: 91.0-100) and 99.4% (95% CI: 96.1-100), respectively. In relation to IgG, the sensitivity and specificity of CLIA against ELISA were, respectively, 97.2% (95% CI: 91.7-99.4) and 92.9% (95% CI: 82.5-97.7), and 95.5% (95% CI: 89.5-98.3) and 100% (95% CI: 91.8-100) after the final classification. CLIA showed excellent sensitivity and specificity in detecting measles IgG and IgM antibodies, eliminating the need to aliquot specimens before carrying out the assay. PMID- 26140434 TI - Chronic illness as biographical contingency? Young people's experiences of asthma. AB - Much research on chronic illness, which views the experience as disruptive, is adult-focused though there is an emerging literature on children's and young people's experiences. Drawing on 31 interviews conducted with young people diagnosed with asthma in south-west Ireland, this article contributes to this literature. The sample includes boys (n = 15) and girls (n = 16) aged between 5 and 17 from the Irish Traveller community and the larger settled community. The study also explores the potential value of what might be called biographical contingency. This concept refers to the way in which a chronic illness may be an 'only sometimes' problem and takes account of the 'now you see it, now you don't' nature of a condition that varies in terms of its symptoms, meanings and consequences. In concluding, we consider the uses and limitations of this concept and the interpretivist paradigm that typically informs qualitative research on the illness experience. PMID- 26140433 TI - The novel cardiac myosin activator omecamtiv mecarbil increases the calcium sensitivity of force production in isolated cardiomyocytes and skeletal muscle fibres of the rat. AB - BACKGROUND AND PURPOSE: Omecamtiv mecarbil (OM) is a novel cardiac myosin activator drug for inotropic support in systolic heart failure. Here we have assessed the concentration-dependent mechanical effects of OM in permeabilized cardiomyocyte-sized preparations and single skeletal muscle fibres of Wistar Kyoto rats under isometric conditions. EXPERIMENTAL APPROACHES: Ca2+ -dependent active force production (Factive ), its Ca2+ sensitivity (pCa50 ), the kinetic characteristics of Ca2+ -regulated activation and relaxation, and Ca2+ independent passive force (Fpassive ) were monitored in Triton X-100-skinned preparations with and without OM (3nM-10 MUM). KEY RESULTS: In permeabilized cardiomyocytes, OM increased the Ca2+ sensitivity of force production (DeltapCa50 : 0.11 or 0.34 at 0.1 or 1 MUM respectively). The concentration-response relationship of the Ca2+ sensitization was bell-shaped, with maximal effects at 0.3-1 MUM OM (EC50 : 0.08 +/- 0.01 MUM). The kinetics of force development and relaxation slowed progressively with increasing OM concentration. Moreover, OM increased Fpassive in the cardiomyocytes with an apparent EC50 value of 0.26 +/- 0.11 MUM. OM-evoked effects in the diaphragm muscle fibres with intrinsically slow kinetics were largely similar to those in cardiomyocytes, while they were less apparent in muscle fibres with fast kinetics. CONCLUSIONS AND IMPLICATIONS: OM acted as a Ca2+ -sensitizing agent with a downstream mechanism of action in both cardiomyocytes and diaphragm muscle fibres. The mechanism of action of OM is connected to slowed activation-relaxation kinetics and at higher OM concentrations increased Fpassive production. PMID- 26140435 TI - N-terminal pro-B-type natriuretic peptide as a marker of hypervolemia and predictor of increased mortality in patients on hemodialysis. AB - INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker of heart failure in the general population. However, its diagnostic value is unclear in hemodialysis (HD) patients owing to renal insufficiency. OBJECTIVES: The aim of the study was to establish the usefulness of NT-proBNP for hydration assessment and the relation of NT-proBNP to the nutritional state and prognosis of survival. PATIENTS AND METHODS: In 321 HD patients (206 men; mean age, 65.1 +/-21.4 years), we assessed NT-proBNP levels, overhydration (OHBIA), and the indices of the nutritional state (using a bioimpedance analysis [BIA]) in relation to cardiac troponin T (cTnT), hemoglobin, albumin, total cholesterol (TC), and C-reactive protein (CRP) levels. The efficacy of HD was assessed using Kt/V, weekly HD dose, and HD session ultrafiltration. The cohort was divided into NT-proBNP quartiles. Patients with 2 NT-proBNP measurements were categorized also into change-over-time subgroups. A follow-up lasted for a median period of 23.8 +/-26.3 months. RESULTS: Relative OHBIA increased across the NT-proBNP quartiles (Q1/Q2/Q3/Q4, 1.31% +/-2.56%/2.06% +/-2.35%/2.92% +/-2.97%/4.62% +/-4.22%; P <0.0001). NT-proBNP was also closely associated with other OH parameters. In addition, there was a significant correlation between NT-proBNP and cTnT (r = 0.55; P <0.0001). Body mass index (BMI) and fat tissue index (FTI) decreased across the quartiles (BMI, 28.5 +/ 7.7/26.0 +/-6.6/25.8 +/-5.4/23.7 +/-5.5 kg/m2; FTI, 14.4 +/-9.0/14.1 +/-7.3/12.3 +/-6.8/11.6 +/-6.1; P <0.001). The highest albumin level was present in Q1 (4.10 +/-0.63/3.99 +/-0.51/3.90 +/-0.62/3.97 +/-0.78 g/dl; P = 0.006). The TC level was the lowest in Q4 (190 +/-60/169 +/-56/173 +/-51/153 +/-56 mg/dl; P = 0.002). The hemoglobin level decreased across the quartiles (11.44 +/-1.25/11.15 +/ 2.50/10.79 +/-1.51/10.45 +/-1.67 g/dl; P = 0.0006). The differences in CRP levels and HD-related parameters were nonsignificant. During the follow-up, 97 deaths were recorded (11/26/21/39, P <0.0001). CONCLUSIONS: NT-proBNP seems to be a useful biomarker of hypervolemia in HD patients. Nevertheless, it has to be interpreted with regard to the patient's individual residual renal function and cardiovascular status. PMID- 26140436 TI - Studies on Chemical Composition, Antimicrobial and Antioxidant Activities of Five Thymus vulgaris L. Essential Oils. AB - This study is aimed at assessing the essential oil composition, total phenolic content, antimicrobial and antioxidant activities of Thymus vulgaris collected in five different area of the Campania Region, Southern Italy. The chemical composition of the essential oils was studied by GC-flame ionization detector (FID) and GC/MS; the biological activities were evaluated through determination of MIC and minimum bactericidal concentration (MBC) and evaluation of antioxidant activity. In total, 134 compounds were identified. The oils were mainly composed of phenolic compounds, and all oils belonged to the chemotype thymol. The antimicrobial activity of the five oils was assayed against ten bacterial strains. The oils showed different inhibitory activity against some Gram-positive pathogens. The total phenol content in the essential oils ranged from 77.6-165.1 mg gallic acid equivalents (GAE)/g. The results reported here may help to shed light on the complex chemotaxonomy of the genus Thymus. These oils could be used in many fields as natural preservatives of food and as nutraceuticals. PMID- 26140437 TI - Synthesis of Novel 1-(4-Substituted pyridine-3-sulfonyl)-3-phenylureas with Potential Anticancer Activity. AB - A series of novel 4-substituted-N-(phenylcarbamoyl)-3-pyridinesulfonamides 11-27 have been synthesized by the reaction of 4-substituted pyridine-3-sulfonamides 2 10 with the appropriate aryl isocyanates in presence of potassium carbonate. The in vitro anticancer activity of compounds 11, 12, 14-21 and 24-26 was evaluated at the U.S. National Cancer Institute and in light of the results, some structure activity relationships were discussed. The most prominent compound, N-[(4 chlorophenyl)carbamoyl]-4-[4-(3,4-dichlorophenyl)piperazin-1-yl]pyridine-3 sulfonamide (21) has exhibited a good activity profile and selectivity toward the subpanels of leukemia, colon cancer and melanoma, with average GI50 values ranging from 13.6 to 14.9 uM. PMID- 26140438 TI - Analysis and Ranking of Protein-Protein Docking Models Using Inter-Residue Contacts and Inter-Molecular Contact Maps. AB - In view of the increasing interest both in inhibitors of protein-protein interactions and in protein drugs themselves, analysis of the three-dimensional structure of protein-protein complexes is assuming greater relevance in drug design. In the many cases where an experimental structure is not available, protein-protein docking becomes the method of choice for predicting the arrangement of the complex. However, reliably scoring protein-protein docking poses is still an unsolved problem. As a consequence, the screening of many docking models is usually required in the analysis step, to possibly single out the correct ones. Here, making use of exemplary cases, we review our recently introduced methods for the analysis of protein complex structures and for the scoring of protein docking poses, based on the use of inter-residue contacts and their visualization in inter-molecular contact maps. We also show that the ensemble of tools we developed can be used in the context of rational drug design targeting protein-protein interactions. PMID- 26140439 TI - The Antioxidant Properties and Inhibitory Effects on HepG2 Cells of Chicory Cultivated Using Three Different Kinds of Fertilizers in the Absence and Presence of Pesticides. AB - The objective of this study was to explore the antioxidant levels and anticancer properties of chicory cultivated using three different kinds of fertilizers (i.e., developed, organic, and chemical) in the presence and absence of pesticides. Phenolic phytochemicals, including total polyphenols and flavonoids, and antioxidant activities, including reducing power, ABTS+ and DPPH radical scavenging activity, were analyzed using several antioxidant assays. HepG2 cell viability was analyzed using the MTT assay. The antioxidant properties of chicory were found to increase when cultivated with chemical fertilizer in the absence of pesticides. On the other hand, antioxidant capacity was higher in chicory cultivated with eco-developed fertilizer even in the presence of pesticides. Chicory grown using eco-developed or organic fertilizer was more effective in suppressing the proliferation of HepG2 cells when compared to chicory grown with chemical fertilizer. This effect was time dependent, regardless of treatment with or without pesticides. In conclusion, the antioxidant activity of chicory were affected by the presence or absence of pesticides. However, developed and organic fertilizers showed a strong anti-proliferative effect against HepG2 cells, regardless of the presence or absence of pesticides. PMID- 26140440 TI - Commercialization of new biotechnology: a systematic review of 16 commercial case studies in a novel manufacturing sector. AB - The 1980s and 1990s saw a major expansion of biotechnology into new areas of science including genomics and recombinant technologies. This was coupled to the widespread emergence of academics into the commercial sector as they were encouraged to spin out companies or commercialize their intellectual property. There were many opportunities to raise investment, and extraordinary success stories were prominent across many areas of technology. The field of plant biotechnology for manufacturing recombinant pharmaceuticals (molecular pharming) emerged and was developed in this period. Like other biotechnologies, this was an exciting new development which offered some very obvious benefits and commercial advantages. In particularly, plant molecular pharming represented a highly novel and potentially disruptive manufacturing technology for recombinant proteins. Twenty-five years on, a series of interviews with senior members of sixteen of the most prominent companies involved in the field provides insight into the original drivers for commercialization, strategic thinking and planning behind key commercial decisions and an insider view into the major reasons for commercial success or failure. These observations and recurring themes identified across a number of commercial ventures remain relevant today, as new biotech companies continue to spin out of the world of academia. PMID- 26140441 TI - Separation, determination and antifungal activity test of the products from a new Bacillus amyloliquefaciens. AB - A new Bacillus amyloliquefaciens named ZJU-2011 was discovered, and the culture supernatant showed a strong inhibitory effect against Candida albicans. In this study, a novel method was developed to purify the antifungal compounds in high purity. The obtained products were analysed by high performance liquid chromatography and proven to be of high purity. Mass spectrometry showed that the molecular weights of the two bioactive components were 270 and 288, respectively, and their structures were determined to be bacilysin and chlorotetaine by using (1)H and (13)C nuclear magnetic resonance spectroscopy. To the best of our knowledge, this is the first time that B. amyloliquefaciens has been reported to produce bacilysin and chlorotetaine simultaneously. The minimum inhibitory concentration of chlorotetaine against six common fungal pathogens were determined to be in the range of 1.8-7.8 MUg/mL. PMID- 26140442 TI - Improved photovoltaic performance and stability of quantum dot sensitized solar cells using Mn-ZnSe shell structure with enhanced light absorption and recombination control. AB - To make quantum-dot-sensitized solar cells (QDSSCs) competitive, photovoltaic parameters comparable to those of other emerging solar cell technologies are necessary. In the present study, ZnSe was used as an alternative to ZnS, one of the most widely used passivation materials in QDSSCs. ZnSe was deposited on a TiO2-CdS-CdSe photoanode to form a core-shell structure, which was more efficient in terms of reducing the electron recombination in QDSSCs. The development of an efficient passivation layer is a requirement for preventing recombination processes in order to attain high-performance and stable QDSSCs. A layer of inorganic Mn-ZnSe was applied to a QD-sensitized photoanode to enhance the adsorption and strongly inhibit interfacial recombination processes in QDSSCs, which greatly improved the power conversion efficiency. Impedance spectroscopy revealed that the combined Mn doping with ZnSe treatment reduces interfacial recombination and increases charge collection efficiency compared with Mn-ZnS, ZnS, and ZnSe. A solar cell based on the CdS-CdSe-Mn-ZnSe photoanode yielded excellent performance with a solar power conversion efficiency of 5.67%, Voc of 0.584 V, and Jsc of 17.59 mA cm(-2). Enhanced electron transport and reduced electron recombination are responsible for the improved Jsc and Voc of the QDSSCs. The effective electron lifetime of the device with Mn-ZnSe was higher than those with Mn-ZnS, ZnSe, and ZnS, leading to more efficient electron-hole separation and slower electron recombination. PMID- 26140443 TI - 1,3-Dipolar cycloadditions of azomethine imines. AB - Azomethine imines are considered 1,3-dipoles of the aza-allyl type which are transient intermediates and should be generated in situ but can also be stable and isolable compounds. They react with electron-rich and electron-poor olefins as well as with acetylenic compounds and allenoates mainly by a [3 + 2] cycloaddition but they can also take part in [3 + 3], [4 + 3], [3 + 2 + 2] and [5 + 3] with different dipolarophiles. These 1,3-dipolar cycloadditions (1,3-DC) can be performed not only under thermal or microwave conditions but also using metallo- and organocatalytic systems. In recent years enantiocatalyzed 1,3 dipolar cycloadditions have been extensively considered and applied to the synthesis of a great variety of dinitrogenated heterocycles with biological activity. Acyclic azomethine imines derived from mono and disubstituted hydrazones could be generated by prototropy under heating or by using Lewis or Bronsted acids to give, after [3 + 2] cycloadditions, pyrazolidines and pyrazolines. Cyclic azomethine imines, incorporating a C-N bond in a ring, such as isoquinolinium imides are the most widely used dipoles in normal and inverse electron demand 1,3-DC allowing the synthesis of tetrahydro-, dihydro- and unsaturated pyrazolo[1,5-a]isoquinolines in racemic and enantioenriched forms with interesting biological activity. Pyridinium and quinolinium imides give the corresponding pyrazolopyridines and indazolo[3,2-a]isoquinolines, respectively. In the case of cyclic azomethine imines with an N-N bond incorporated into a ring, N-alkylidene-3-oxo-pyrazolidinium ylides are the most popular stable and isolated dipoles able to form dinitrogen-fused saturated and unsaturated pyrazolopyrazolones as racemic or enantiomerically enriched compounds present in many pharmaceuticals, agrochemicals and other useful chemicals. PMID- 26140444 TI - MOF derived composites for cathode protection: coatings of LiCoO2 from UiO-66 and MIL-53 as ultra-stable cathodes. AB - A mechanochemical synthetic method of preparing LiCoO2 coated by MOF-derived metal oxide composites is introduced. Mono-dispersed ZrO2 and Al2O3 are applied as protection layers. These composites show 148 mA h g(-1) at a current density of 2325 mA g(-1) and excellent thermal stability (55 degrees C). PMID- 26140445 TI - Female and male human babies have distinct blood metabolomic patterns. AB - A sex-gender approach in laboratory medicine is scarce; furthermore, the influence of sex on acylcarnitines and amino acid levels at birth has not been thoroughly investigated, even if sex impacts on newborn screening. We aimed to establish the influence of sex on amino acids and acylcarnitines levels in male and female newborns. Amino acids and acylcarnitines were analysed in dried blood spots using tandem mass spectrometry in male and female newborns. Data were analysed before and after body weight correction also using principal components analysis. This retrospective analytical study showed that females had small but significantly higher levels of amino acids and the correction for body weight amplified these differences. Acylcarnitines were overall higher in males before body weight correction with the exception of isovalerylcarnitine + methylbutyrylcarnitine (C5), which was significantly higher in females. Body weight correction decreased the sex differences in C5. Principal component analysis showed that both amino acids and acylcarnitines were necessary to describe the model for females, whereas only acylcarnitines were required for males. These metabolomics data underline the importance of including sex as a variable in future investigations of circulating metabolites; the existence of sex differences highlights the need for setting distinct reference values for female and male neonates in metabolite concentration. PMID- 26140446 TI - Asymmetric synthesis of optically active methyl-2-benzamido-methyl-3-hydroxy butyrate by robust short-chain alcohol dehydrogenases from Burkholderia gladioli. AB - Three short-chain alcohol dehydrogenases from Burkholderia gladioli were discovered for their great potential in the dynamic kinetic asymmetric transformation of methyl 2-benzamido-methyl-3-oxobutanoate, and their screening against varied organic solvents and substrates. This is the first report of recombinant enzymes capable of achieving this reaction with the highest enantio- and diastereo-selectivity. PMID- 26140447 TI - Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents. AB - In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on children and adolescents, and substantial clinical experience. This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children. These recommendations are relevant to families, clinicians, and investigators. After a brief review of the 1995 statement and major changes in genetic technologies in recent years, this statement offers points to consider on a broad range of test technologies and their applications in clinical medicine and research. Recommendations are also made for record and communication issues in this domain and for professional education. PMID- 26140448 TI - A Joint Location-Scale Test Improves Power to Detect Associated SNPs, Gene Sets, and Pathways. AB - Gene-based, pathway, and other multivariate association methods are motivated by the possibility of GxG and GxE interactions; however, accounting for such interactions is limited by the challenges associated with adequate modeling information. Here we propose an easy-to-implement joint location-scale (JLS) association testing framework for single-variant and multivariate analysis that accounts for interactions without explicitly modeling them. We apply the JLS method to a gene-set analysis of cystic fibrosis (CF) lung disease, which is influenced by multiple environmental and genetic factors. We identify and replicate an association between the constituents of the apical plasma membrane and CF lung disease (p = 0.0099 and p = 0.0180, respectively) and highlight a role for the SLC9A3-SLC9A3R1/2-EZR complex in contributing to CF lung disease. Many association studies could benefit from re-analysis with the JLS method that leverages complex genetic architecture for SNP, gene, and pathway identification. Analytical verification, simulation, and additional proof-of-principle applications support our approach. PMID- 26140450 TI - Evaluation of current clinical target volume definitions for glioblastoma using cell-based dosimetry stochastic methods. AB - OBJECTIVE: Determination of an optimal clinical target volume (CTV) is complex and remains uncertain. The aim of this study was to develop a glioblastoma multiforme (GBM) model to be used for evaluation of current CTV practices for external radiotherapy. METHODS: The GBM model was structured as follows: (1) a Geant4 cellular model was developed to calculate the absorbed dose in individual cells represented by cubic voxels of 20 MUm sides. The system was irradiated with opposing 6 MV X-ray beams. The beams encompassed planning target volumes corresponding to 2.0- and 2.5-cm CTV margins; (2) microscopic extension probability (MEP) models were developed using MATLAB((r)) 2012a (MathWorks((r)), Natick, MA), based on clinical studies reporting on GBM clonogenic spread; (3) the cellular dose distribution was convolved with the MEP models to evaluate cellular survival fractions (SFs) for both CTV margins. RESULTS: A CTV margin of 2.5 cm, compared to a 2.0-cm CTV margin, resulted in a reduced total SF from 12.9% +/- 0.9% to 3.6% +/- 0.2%, 5.5% +/- 0.4% to 1.2% +/- 0.1% and 11.1% +/- 0.7% to 3.0% +/- 0.2% for circular, elliptical and irregular MEP distributions, respectively. CONCLUSION: A Monte Carlo model was developed to quantitatively evaluate the impact of GBM CTV margins on total and penumbral SF. The results suggest that the reduction in total SF ranges from 3.5 to 5, when the CTV is extended by 0.5 cm. ADVANCES IN KNOWLEDGE: The model provides a quantitative tool for evaluation of different CTV margins in terms of cell kill efficacy. Cellular platform of the tool allows future incorporation of cellular properties of GBM. PMID- 26140449 TI - Disentangling the Effects of Colocalizing Genomic Annotations to Functionally Prioritize Non-coding Variants within Complex-Trait Loci. AB - Identifying genomic annotations that differentiate causal from trait-associated variants is essential to fine mapping disease loci. Although many studies have identified non-coding functional annotations that overlap disease-associated variants, these annotations often colocalize, complicating the ability to use these annotations for fine mapping causal variation. We developed a statistical approach (Genomic Annotation Shifter [GoShifter]) to assess whether enriched annotations are able to prioritize causal variation. GoShifter defines the null distribution of an annotation overlapping an allele by locally shifting annotations; this approach is less sensitive to biases arising from local genomic structure than commonly used enrichment methods that depend on SNP matching. Local shifting also allows GoShifter to identify independent causal effects from colocalizing annotations. Using GoShifter, we confirmed that variants in expression quantitative trail loci drive gene-expression changes though DNase-I hypersensitive sites (DHSs) near transcription start sites and independently through 3' UTR regulation. We also showed that (1) 15%-36% of trait-associated loci map to DHSs independently of other annotations; (2) loci associated with breast cancer and rheumatoid arthritis harbor potentially causal variants near the summits of histone marks rather than full peak bodies; (3) variants associated with height are highly enriched in embryonic stem cell DHSs; and (4) we can effectively prioritize causal variation at specific loci. PMID- 26140452 TI - Synthesis and antifungal activity evaluation of new heterocycle containing amide derivatives. AB - A series of heterocycle containing amide derivatives (1-28) were synthesised by the combination of acyl chlorides (1a, 2a) and heterocyclic/homocyclic ring containing amines, and their in vitro antifungal activity was evaluated against five plant pathogenic fungi, namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum. Results of antifungal activity analysis indicated that some of the products showed good to excellent antifungal activity, as compound 2 showed excellent activity against G. zeae and R. solani and potent activity against H. maydi, B. cinerea and S. sclerotiorum, and compounds 1, 8 and 10 also displayed excellent antifungal potential against H. maydi, B. cinerea and S. sclerotiorum and good activity against R. solani when compared with the standard carbendazim. PMID- 26140454 TI - Under Pressure: Financial Effect of the Hospital-Acquired Conditions Initiative-A Statewide Analysis of Pressure Ulcer Development and Payment. AB - OBJECTIVES: To assess the financial effect of the 2008 Hospital-Acquired Conditions Initiative (HACI) pressure ulcer payment changes on Medicare, other payers, and hospitals. DESIGN: Retrospective before-and-after study of all-payer statewide administrative data for more than 2.4 million annual adult discharges in 2007 and 2009 using the Healthcare Cost and Utilization Project State Inpatient Datasets for California. How often and by how much the 2008 payment changes for pressure ulcers affected hospital payment was assessed. SETTING: Nonfederal acute care California hospitals (N = 311). PARTICIPANTS: Adults discharged from acute-care hospitals. MEASUREMENTS: Pressure ulcer rates and hospital payment changes. RESULTS: Hospital-acquired pressure ulcer rates were low in 2007 (0.28%) and 2009 (0.27%); present-on-admission pressure ulcer rates increased from 2.3% in 2007 to 3.0% in 2009. According to clinical stage of pressure ulcer (available in 2009), hospital-acquired Stage III and IV ulcers occurred in 603 discharges (0.02%); 60,244 discharges (2.42%) contained other pressure ulcer diagnoses. Payment removal for Stage III and IV hospital-acquired ulcers reduced payment in 75 (0.003%) discharges, for a statewide payment decrease of $310,444 (0.001%) for all payers and $199,238 (0.001%) for Medicare. For all other pressure ulcers, the Hospital-Acquired Conditions Initiative reduced hospital payment in 20,246 (0.81%) cases (including 18,953 cases with present-on-admission ulcers), reducing statewide payment by $62,538,586 (0.21%) for all payers and $47,237,984 (0.32%) for Medicare. CONCLUSION: The total financial effect of the 2008 payment changes for pressure ulcers was negligible. Most payment decreases occurred by removal of comorbidity payments for present-on admission pressure ulcers other than Stages III and IV. The removal of payment for hospital-acquired Stage III and IV ulcers by implementation of the HACI policy was 1/200th that of the removal of payment for other types of pressure ulcers that occurred in implementation of the Hospital-Acquired Conditions Initiative. PMID- 26140455 TI - Frequency, characteristics, and perceived functions of emotional future thinking in daily life. AB - While many thoughts and mental images that people form about their personal future refer to emotionally significant events, there is still little empirical data on the frequency and nature of emotional future-oriented thoughts (EmoFTs) that occur in natural settings. In the present study, participants recorded EmoFTs occurring in daily life and rated their characteristics, emotional properties, and perceived functions. The results showed that EmoFTs are frequent, occur in various contexts, and are perceived to fulfil important functions, mostly related to goal pursuit and emotion regulation. When distinguishing between anticipatory and anticipated emotions (i.e., emotions experienced in the present versus emotions expected to occur in the future), a positivity bias in the frequency of EmoFTs was found to be restricted to anticipated emotions. The representational format and perceived function of EmoFTs varied according to their affective valence, and the intensity of anticipatory and anticipated emotions were influenced by the personal importance and amount of visual imagery of EmoFTs. Mood states preceding EmoFTs influenced their emotional components, which, in turn, impacted ensuing mood states. Overall, these findings shed further light on the emotional properties of future-oriented thoughts that are experienced in daily life. PMID- 26140453 TI - Efficacy of WHO recommendation for continued breastfeeding and maternal cART for prevention of perinatal and postnatal HIV transmission in Zambia. AB - INTRODUCTION: To prevent mother-to-child transmission (MTCT) of HIV in developing countries, new World Health Organization (WHO) guidelines recommend maternal combination antiretroviral therapy (cART) during pregnancy, throughout breastfeeding for 1 year and then cessation of breastfeeding (COB). The efficacy of this approach during the first six months of exclusive breastfeeding has been demonstrated, but the efficacy of this approach beyond six months is not well documented. METHODS: A prospective observational cohort study of 279 HIV-positive mothers was started on zidovudine/3TC and lopinavir/ritonavir tablets between 14 and 30 weeks gestation and continued indefinitely thereafter. Women were encouraged to exclusively breastfeed for six months, complementary feed for the next six months and then cease breastfeeding between 12 and 13 months. Infants were followed for transmission to 18 months and for survival to 24 months. Text message reminders and stipends for food and transport were utilized to encourage adherence and follow-up. RESULTS: Total MTCT was 9 of 219 live born infants (4.1%; confidence interval (CI) 2.2-7.6%). All breastfeeding transmissions that could be timed (5/5) occurred after six months of age. All mothers who transmitted after six months had a six-month plasma viral load >1,000 copies/ml (p<0.001). Poor adherence to cART as noted by missed dispensary visits was associated with transmission (p=0.04). Infant mortality was lower after six months of age than during the first six months of life (p=0.02). The cumulative rate of infant HIV infection or death at 18 months was 29/226 (12.8% 95 CI: 7.5 20.8%). CONCLUSIONS: Maternal cART may limit MTCT of HIV to the UNAIDS target of <5% for eradication of paediatric HIV within the context of a clinical study, but poor adherence to cART and follow-up can limit the benefit. Continued breastfeeding can prevent the rise in infant mortality after six months seen in previous studies, which encouraged early COB. PMID- 26140456 TI - Generation of semicarbazide from natural azine development in foods, followed by reaction with urea compounds. AB - This paper proposes a mechanism to explain the trace levels of natural semicarbazide occasionally observed in foods. The analytical derivative of semicarbazide, 2-nitrobenzaldehyde semicarbazone, is often measured as a metabolite marker to detect the widely banned antibiotic nitrofurazone. However, this marker is not specific as semicarbazide may be present in foods for several reasons other than exposure to nitrofurazone. In some cases, an entirely natural origin of semicarbazide is suspected, although up until now there was no explanation about how semicarbazide could occur naturally. In this work, semicarbazide is proposed as being generated from natural food compounds via an azine intermediate. Hydrazine, in the form of azines or hydrazones, may be generated in dilute aqueous solution from the natural food compounds ammonia, hydrogen peroxide and acetone, following known oxidation chemistry. When this mixture was prepared in the presence of ureas such as allantoin, urea, biuret or hydroxyurea, and then analysed by the standard method for the determination of semicarbazide, 2-nitrobenzaldehyde semicarbazone was detected. 2 Nitrobenzaldehyde aldazine was also found, and it may be a general marker for azines in foods. This proposal, that azine formation is central to semicarbazide development, provides a convergence of the published mechanisms for semicarbazide. The reaction starts with hydrogen peroxide, peracetic acid, atmospheric oxygen or hypochlorite; generates hydrazine either by an oxaziridine intermediate or via the chlorination of ammonia; and then either route may converge on azine formation, followed by reaction with a urea compound. Additionally, carbamate ion may speculatively generate semicarbazide by reaction with hydrazine, which might be a significant route in the case of the hypochlorite treatment of foods or food contact surfaces. Significantly, detection of 2-nitrobenzaldehyde semicarbazone may be somewhat artefactual because semicarbazide can form during the acid conditions of analysis, which can free hydrazine in the presence of urea compounds. PMID- 26140458 TI - Impact of epilepsy surgery on development of preschool children: identification of a cohort likely to benefit from early intervention. AB - OBJECT: Outcomes of focal resection in young children with early-onset epilepsy are varied in the literature due to study differences. In this paper, the authors sought to define the effect of focal resection in a small homogeneous sample of children who were otherwise cognitively intact, but who required early surgical treatment. Preservation of and age-appropriate development of intelligence following focal resection was hypothesized. METHODS: Cognitive outcome after focal resection was retrospectively reviewed for 15 cognitively intact children who were operated on at the ages of 2-6 years for lesion-related, early-onset epilepsy. Intelligence was tested prior to and after surgery. Effect sizes and confidence intervals for means and standard deviations were used to infer changes and differences in intelligence between 1) groups (pre vs post), 2) left versus right hemisphere resections, and 3) short versus long duration of seizures prior to resection. RESULTS: No group changes from baseline occurred in Full Scale, verbal, or nonverbal IQ. No change from baseline intelligence occurred in children who underwent left or right hemisphere surgery, including no group effect on verbal scores following surgery in the dominant hemisphere. Patients with seizure durations of less than 6 months prior to resection showed improvement from their presurgical baseline in contrast to those with seizure duration of greater than 6 months prior to surgery, particularly in Wechsler Full Scale IQ and nonverbal intelligence. CONCLUSIONS: This study suggests that surgical treatment of focal seizures in cognitively intact preschool children is likely to result in seizure remediation, antiepileptic drug discontinuation, and no significant decrement in intelligence. The latter finding is particularly significant in light of the longstanding concern associated with performing resections in the language-dominant hemisphere. Importantly, shorter seizure duration prior to resection can result in improved cognitive outcome, suggesting that surgery for this population should occur sooner to help improve intelligence outcomes. PMID- 26140459 TI - Investigation of biochemical property changes in activation-induced CD8+ T cell apoptosis using Raman spectroscopy. AB - The study was to investigate the changes in biochemical properties of activated mature CD8+ T cells related to apoptosis at a molecular level. We confirmed the activation and apoptosis of CD8+ T cells by fluorescence-activated cell sorting and atomic force microscopy and then performed Raman spectral measurements on activated mature CD8+ T cells and cellular deoxyribose nucleic acid (DNA). In the activated mature CD8+ T cells, there were increases in protein spectra at 1002 and 1234 cm -1 . In particular, to assess the apoptosis-related DNA spectral signatures, we investigated the spectra of the cellular DNA isolated from resting and activated mature CD8+ T cells. Raman spectra at 765 to 786 cm -1 and 1053 to 1087 cm -1 were decreased in activated mature DNA. In addition, we analyzed Raman spectrum using the multivariate statistical method including principal component analysis. Raman spectra of activated mature DNA are especially well discriminated from those of resting DNA. Our findings regarding the biochemical and structural changes associated with apoptosis in activated mature T cells and cellular DNA according to Raman spectroscopy provide important insights into allospecific immune responses generated after organ transplantation, and may be useful for therapeutic manipulation of the immune response PMID- 26140460 TI - Analysis of the change in peak corneal temperature during excimer laser ablation in porcine eyes. AB - The objective is to characterize the impact of different ablation parameters on the thermal load during corneal refractive surgery by means of excimer laser ablation on porcine eyes. One hundred eleven ablations were performed in 105 porcine eyes. Each ablation was recorded using infrared thermography and analyzed mainly based on the two tested local frequencies (40 Hz, clinical local frequency; 1000 Hz, no local frequency). The change in peak corneal temperature was analyzed with respect to varying ablation parameters [local frequency, system repetition rate, pulse energy, optical zone (OZ) size, and refractive correction]. Transepithelial ablations were also compared to intrastromal ablations. The average of the baseline temperature across all eyes was 20.5 degrees C+/-1.1 (17.7 degrees C to 22.2 degrees C). Average of the change in peak corneal temperature for all clinical local frequency ablations was 5.8 degrees C+/-0.8 (p=3.3E-53 to baseline), whereas the average was 9.0 degrees C+/-1.5 for all no local frequency ablations (p=1.8E-35 to baseline, 1.6E-16 to clinical local frequency ablations). A logarithmic relationship was observed between the changes in peak corneal temperature with increasing local frequency. For clinical local frequency, change in peak corneal temperature was comparatively flat (r 2 =0.68 with a range of 1.5 degrees C) with increasing system repetition rate and increased linearly with increasing OZ size (r 2 =0.95 with a range of 2.4 degrees C). Local frequency controls help maintain safe corneal temperature increase during excimer laser ablations. Transepithelial ablations induce higher thermal load compared to intrastromal ablations, indicating a need for stronger thermal controls in transepithelial refractive procedures. PMID- 26140461 TI - Photobiomodulation with low-level diode laser promotes osteoblast migration in an in vitro micro wound model. AB - Laser photobiomodulation can improve bone healing, but well-defined treatment parameters are lacking. Saos-2 human osteoblast-like cells were subjected to an in vitro scratch-wound healing assay and irradiated by a 915-nm gallium-aluminum arsenide diode laser for 0, 48, 96, and 144 s using doses of, respectively, 0, 5, 10, and 15 J/cm(2) . Wound area was measured after 4, 24, 48, and 72 h. Cell viability, DNA content, gene expression, and release of bone-related proteins were evaluated after 24, 48, and 72 h. Laser significantly improved wound healing compared with nonirradiated controls. Cells treated with laser doses of 5 and 10 J/cm(2) reached wound closure after 72 h, followed by 15 J/cm(2) after 96 h. With the cell proliferation inhibitor Mitomycin C, the doses of 10 and 15 J/cm(2) maintained an improved wound healing compared with controls. Laser increased collagen type 1 gene expression with higher doses inducing a longer-lasting effect, whereas transforming growth factor-beta 1 showed comparable or decreased levels in irradiated versus nonirradiated groups, with no effect on protein release. This study demonstrated that laser photobiomodulation at 915 nm promoted wound healing mainly through stimulation of cell migration and collagen deposition by osteoblasts. PMID- 26140462 TI - Core-Lexicon and Main-Concept Production During Picture-Sequence Description in Adults Without Brain Damage and Adults With Aphasia. AB - PURPOSE: We sought to identify the core lexicon of a picture-description task using transcripts from the AphasiaBank database and to determine differences in core-lexicon usage between control speakers and persons with aphasia (PWAs). We also investigated the relationship between core lexicon and an established discourse measure, main-concept analysis. METHOD: A core lexicon was developed by identifying lemmas produced by 92 control speakers. Transcripts were scored-165 control transcripts and 238 PWA transcripts-using the core lexicon and a recently developed main-concept list. Median tests examined differences between controls, PWAs, and aphasia subtypes. Spearman's correlations assessed the relationship between core-lexicon and main-concept performance. RESULTS: A 24-item core lexicon was identified. Significant differences were found between control speakers and PWAs, and between aphasia subtypes, for core-lexicon and main concept scores. Core-lexicon and main-concept performance was significantly and positively correlated for all groups. CONCLUSIONS: We report the development of a core lexicon, differences in core-lexicon usage between speakers, and the relationship between core-lexicon and main-concept scores. Research is needed to determine the clinical utility and psychometric properties of these discourse measures and their potential contribution to multilevel discourse analysis of functional communication. PMID- 26140463 TI - Evaluation of changes in magnetic resonance images following 24 and 52 weeks of treatment of rheumatoid arthritis with infliximab, tocilizumab, or abatacept. AB - OBJECTIVES: To compare MRI findings in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (DMARDs). METHODS: The study subjects were 43 RA patients treated with biologic DMARDs (13 with infliximab, 15 with tocilizumab, and 15 with abatacept). They were evaluated using Simplified Disease Activity Index (SDAI) and low-field extremity MRI at baseline, and at 24 weeks and 52 weeks of treatment. RESULTS: Synovitis scores were significantly lower by 24 weeks in all groups, compared with baseline (P < 0.05). Significant improvement in bone marrow edema (BME) scores were noted from baseline to 24 weeks in infliximab and abatacept groups (P < 0.05), but from 24 weeks to 52 weeks in tocilizumab group (P < 0.01). No significant change was found in erosion score. The synovitis score at baseline correlated significantly with SDAI at 24 weeks (P < 0.05), and the score at 24 weeks correlated significantly with SDAI at 52 weeks (P < 0.05). CONCLUSIONS: The results suggest that the inflammatory improvement by infliximab and abatacept may express earlier than those by tocilizumab, despite similar improvement in SDAI. MRI-detected synovitis could be a useful predictor of SDAI at 24 weeks of treatment. The MRI remains the best tool to detect and assess the effects of biologic DMARDs in RA. PMID- 26140464 TI - Comparison of golimumab 100-mg monotherapy to golimumab 50 mg plus methotrexate in patients with rheumatoid arthritis: Results from a multicenter, cohort study. AB - OBJECTIVE: The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA). METHODS: The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17-87) years; median (range) disease duration, 8 (0.6-48) years) started on GLM. Eighty three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2-16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group). Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM. RESULTS: There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group. CONCLUSIONS: GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX. PMID- 26140465 TI - Tofacitinib can decrease anti-DNA antibody titers in inactive systemic lupus erythematosus complicated by rheumatoid arthritis. PMID- 26140466 TI - The process of collecting and evaluating evidences for the development of Guidelines for the management of rheumatoid arthritis, Japan College of Rheumatology 2014: Utilization of GRADE approach. AB - OBJECTIVES: To describe the process of collecting and evaluating evidence for treating rheumatoid arthritis (RA) for developing clinical practice guidelines (CPGs) for rheumatologists in Japan. METHODS: The task force comprised rheumatologists, epidemiologists, health economists, and patients. First, the critical outcomes were determined according to a three-round Delphi method, and eight topics with 88 clinical questions (CQs) were formulated. A systematic review of CQs was conducted using the Cochran Database of Systematic Reviews, MEDLINE, and Japana Centra Revvo Medicina (2003-2012). A questionnaire survey and focus group interview were performed to capture the patients' values and preferences. Data from the National Health Insurance drug price list and product information provided by pharmaceutical companies were collected to evaluate drug cost and safety. The GRADE approach was used to describe the evidence quality and determine the strength of recommendations. Recommendations were developed using a modified Delphi method by a multidisciplinary panel including patients. RESULTS: Eight meetings and frequent e-mail communications were conducted to draft a quality assessment of evidence and recommendations. For 88 CQs, recommendation statements were determined. CONCLUSIONS: Using the GRADE approach, new CPGs successfully addressed important clinical issues for treating RA patients. Timely updating of recommendations should be routinely considered. PMID- 26140467 TI - Disease activity early in treatment as a predictor of future low disease activity in RA patients treated with iguratimod. AB - OBJECTIVES: This retrospective observational study aimed to examine the efficacy of iguratimod with and without concomitant methotrexate (MTX) and to estimate the adequate observational period for predicting low disease activity (LDA) achievement at 24 weeks in patients with rheumatoid arthritis (RA). METHODS: All patients treated with iguratimod were registered in a Japanese multicenter registry. Multivariate analyses were performed to identify predictive factors for LDA achievement at 24 weeks. Receiver operating characteristic (ROC) curve analyses were performed to estimate the association of 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) at each time point with achievement of LDA at 24 weeks and determine a cut-off for DAS28-ESR. RESULTS: A total of 123 patients were treated with iguratimod with (n = 65) or without (n = 58) MTX. Iguratimod therapy resulted in significant clinical improvement in both groups. Multivariate analysis revealed that DAS28-ESR at each time point was an independent significant predictor of LDA achievement at 24 weeks. Cut-off values of DAS28-ESR at 12 weeks based on ROC curves were 3.2 and 3.6 in patients with and without MTX, respectively. CONCLUSIONS: Iguratimod was effective in RA patients in clinical practice. Our results suggest that 12 weeks may be a sufficient period to judge the medium-term efficacy of iguratimod in patients treated with and without MTX. PMID- 26140468 TI - Comment on "Corticosteroid-sparing effect of tacrolimus in the initial treatment of dermatomyositis and polymyositis" by Yokoyama et al. PMID- 26140469 TI - Impact of IL-1 inhibition on fatigue associated with autoinflammatory syndromes. AB - Cryopyrin-associated periodic syndromes (CAPS) is a rare group of autoinflammatory disorders that includes familial cold autoinflammatory syndrome or FCAS, Muckle-wells syndrome or MWS, and neonatal-onset multisystem inflammatory disease or NOMID. CAPS is caused by a mutation in the NOD-like receptor family, pyrin domain containing 3 (NLRP3) gene. This ultimately leads to increased production of interleukin (IL)-1beta. IL-1beta is a biologically active member of the IL-1 family. It is not only a pro-inflammatory cytokine responsible for features such as fever, rash, and arthritis, but is also a major mediator in the central pathways of fatigue. Fatigue is a major component of CAPS and is associated with severely compromised quality of life. In clinical studies, fatigue was measured using functional assessment of chronic illness therapy fatigue or FACIT-F and short form-36 or SF-36, physical component score instruments. These questionnaires can also be used to monitor improvement of fatigue following initiation of therapy. IL-1 inhibitors block the IL-1 signaling cascade, thereby preventing systemic inflammation in CAPS. The decrease in systemic inflammation is accompanied by improvement in fatigue. PMID- 26140470 TI - Risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis. AB - OBJECTIVE: No available anti-osteoporotic medication has been shown to completely prevent declines in bone mineral density (BMD) and the resulting increased risk of fracture. The objective of this study was to investigate the risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis (RA). METHODS: A retrospective cohort study of 103 patients with RA and osteoporosis was conducted. Patients were divided into two groups for comparison: those whose osteoporosis treatment was effective and those whose treatment failed. Risk factors for treatment failure were identified by univariate and multivariate logistic regression using variables that differed significantly between the groups. RESULTS: Osteoporosis treatment failed in 66 of 103 patients (64.1%). During 14.01 months of follow-up, non-adherence to bisphosphonate use was the most powerful risk factor for treatment failure. Daily glucocorticoid dosage >= 7.5 mg/day before the first BMD measurement, immobilization > 3 months, and Disease Activity Score in 28 joints (DAS28) >= 3.2 were also significantly related to treatment failure. CONCLUSION: Our findings indicate that osteoporosis treatment fails frequently in RA patients and adherence to bisphosphonate use, daily glucocorticoid dosage, immobilization, and DAS28 score should be taken into consideration when treating osteoporotic patients with RA. PMID- 26140471 TI - Predictive grade of ultrasound synovitis for diagnosing rheumatoid arthritis in clinical practice and the possible difference between patients with and without seropositivity. AB - OBJECTIVE: To determine the degree of contribution and the contributing factors of ultrasound in the diagnosis of rheumatoid arthritis (RA) in daily clinical practice and the predictive differences depending on seropositivity. METHODS: We included 122 patients who presented with the main complaint of finger and/or wrist joint pain but for whom no definite diagnosis was reached or treatment strategy was provided. Ultrasound was performed on at least 22 joints (both wrist joints, proximal interphalangeal joint, and metacarpophalangeal joints), and patients were followed for >=6 months. Factors contributing to RA diagnosis were determined and compared between seropositive and seronegative RA patients. RESULTS: RA was diagnosed in 52 of 122 patients, in whom the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria (odds ratio [OR] = 4.74, P = 0.01) and gray scale (GS) grade of 3 (OR = 3.64, P = 0.04) for >= 1 joint were the contributing factors. In seropositive RA, the ACR/EULAR criteria (OR = 15.53, P < 0.001) and power Doppler (PD) >= 2 for >= 1 joint (OR = 10.48, P = 0.0048) were the contributing factors. In seronegative RA, PD >= 1 for >= 1 joint contributed the most (OR = 20.00, P = 0.0044), but the ACR/EULAR criteria did not contribute to RA diagnosis (P = 0.57). CONCLUSION: Ultrasound findings contributed to RA diagnosis in clinical practice. The contributing factors are different in the presence or absence of seropositivity, and ultrasound complementation was particularly useful in seronegative RA patients. PMID- 26140472 TI - (18)F-FDG and (18)F-NaF PET/CT demonstrate coupling of inflammation and accelerated bone turnover in rheumatoid arthritis. AB - OBJECTIVE: To compare the findings in rheumatoid arthritis (RA)-affected joints between (18)F-fluorodeoxyglucose (FDG) and (18)F-fluoride (NaF) positron emission tomography (PET)/computed tomography (CT). METHODS: We enrolled twelve RA patients who started a new biologic agent (naive 9 and switch 3). At entry, both hands were examined by (18)F-FDG PET/CT, (18)F-NaF PET/CT, and X-ray. Intensity of PET signals was determined by standardized uptake value max (SUVmax) in metacarpophalangeal (MCP), proximal interphalangeal (PIP), and ulnar, medial, and radial regions of the wrists. Hand X-rays were evaluated according to the Genant modified Sharp score at baseline and 6 months. RESULTS: Both (18)F-FDG and (18)F NaF accumulated in RA-affected joints. The SUVmax of (18)F-FDG correlated with that of (18)F-NaF in individual joints (r = 0.65), though detail distribution was different between two tracers. (18)F-NaF and (18)F-FDG signals were mainly located in the bone and the surrounding soft tissues, respectively. The sum of SUVmax of (18)F-NaF correlated with disease activity score in 28 joint (DAS28), modified health assessment questionnaire (MHAQ), and radiographic progression. (18)F-FDG and (18)F-NaF signals were associated with the presence of erosions, particularly progressive ones. CONCLUSION: Our data show that both (18)F-FDG and (18)F-NaF PET signals were associated with RA-affected joints, especially those with ongoing erosive changes. PMID- 26140473 TI - Reduction in asymmetric dimethylarginine plasma levels by coenzyme Q10 supplementation in patients with type 2 diabetes mellitus. AB - AIM: According to many studies, supplementation with Coenzyme Q10 (CoQ10) yields beneficial results in terms of endothelial function in type 2 diabetes mellitus. Despite these promising results, data elucidating the effect of CoQ10 on plasma levels of asymmetric dimethylarginine (ADMA), as a recently discussed cardiovascular risk factor, is lacking. This study was designed to investigate the effect of CoQ10 supplementation on endothelial function, specifically by evaluating plasma ADMA levels. METHODS: Sixty-four type 2 diabetic patients were randomly assigned to two groups; either receiving 200mg/d oral dose of CoQ10 (N.=31) or receiving placebo (N.=33) for 12 weeks. Clinical and biochemical assessments were performed before and after the trial for evaluating ADMA, serum nitrite and nitrate (NOx), hemoglobin A1c and lipid profile. RESULTS: The intervention resulted in a significant improvement in ADMA, NOx , low-density lipoprotein and hemoglobin A1c levels in CoQ10 compared to placebo group. Interestingly, difference in changes of these parameters were also significant (P=0.01, 0.03, 0.04 and 0.03, respectively). CONCLUSION: Supplementation with CoQ10 yields beneficial effects on ADMA levels, leading to decreased diabetic cardiovascular events. PMID- 26140474 TI - A constant threat for HIV: Fc-engineering to enhance broadly neutralizing antibody activity for immunotherapy of the acquired immunodeficiency syndrome. AB - Passive immunotherapy with polyclonal or hyperimmune serum immunoglobulin G (IgG) preparations provides an efficient means of protecting immunocompromised patients from microbial infections. More recently, the use of passive immunotherapy to prevent or to treat established infections with the human immunodeficiency virus (HIV) has gained much attention, due to promising preclinical data obtained in monkey and humanized mouse in vivo model systems, demonstrating that the transfer of HIV-specific antibodies can not only prevent HIV infection, but also diminish virus load during chronic infection. Furthermore, an array of broadly neutralizing HIV-specific antibodies has become available and the importance of the IgG constant region as a critical modulator of broadly neutralizing activity has been demonstrated. The aim of this review is to summarize the most recent findings with regard to the molecular and cellular mechanisms responsible for antibody-mediated clearance of HIV infection, and to discuss how this may help to improve HIV therapy via optimizing Fcgamma-receptor-dependent activities of HIV specific antibodies. PMID- 26140475 TI - Sensory and metabolic profiles of "Fuji" apples (Malus domestica Borkh.) grown without synthetic agrochemicals: the role of ethylene production. AB - Flavors of "Fuji" apple cultivated with or without synthetic agrochemicals were compared using quantitative descriptive analyses (QDA) and metabolite profiling for 3 seasons. Experimental plots included conventional crops (with agrochemicals) and organic crops (without agrochemicals) at our institute and organic and conventional farms. Additionally, mass market samples were analyzed. Organic apples were weak in sweetness and floral characteristics and had enhanced green and sour flavors. Most esters and sugars were present in lower concentrations in organic than in conventional apples. Close relation of principal component 1 of QDA and metabolite profiles, to ethylene production suggested that ethylene is considerably involved in flavor synthesis. Reduced ethylene associated with immaturity accounted for insufficient flavor synthesis and weak aroma and flavor attributes of organic apples. Furthermore, organic apples from the farm were more flavorsome than those from the institute in 2012, suggesting possible recovery of ethylene production after a long organic cultivation period. PMID- 26140476 TI - Temperature Gradient Approach for Rapidly Assessing Sensor Binding Kinetics and Thermodynamics. AB - We report a highly resolved approach for quantitatively measuring the temperature dependence of molecular binding in a sensor format. The method is based on surface plasmon resonance (SPR) imaging measurements made across a spatial temperature gradient. Simultaneous recording of sensor response over the range of temperatures spanned by the gradient avoids many of the complications that arise in the analysis of SPR measurements where temperature is varied. In addition to simplifying quantitative analysis of binding interactions, the method allows the temperature dependence of binding to be monitored as a function of time, and provides a straightforward route for calibrating how temperature varies across the gradient. Using DNA hybridization as an example, we show how the gradient approach can be used to measure the temperature dependence of binding kinetics and thermodynamics (e.g., melt/denaturation profile) in a single experiment. PMID- 26140477 TI - On the path to genetic novelties: insights from programmed DNA elimination and RNA splicing. AB - Understanding how genetic novelties arise is a central goal of evolutionary biology. To this end, programmed DNA elimination and RNA splicing deserve special consideration. While programmed DNA elimination reshapes genomes by eliminating chromatin during organismal development, RNA splicing rearranges genetic messages by removing intronic regions during transcription. Small RNAs help to mediate this class of sequence reorganization, which is not error-free. It is this imperfection that makes programmed DNA elimination and RNA splicing excellent candidates for generating evolutionary novelties. Leveraging a number of these two processes' mechanistic and evolutionary properties, which have been uncovered over the past years, we present recently proposed models and empirical evidence for how splicing can shape the structure of protein-coding genes in eukaryotes. We also chronicle a number of intriguing similarities between the processes of programmed DNA elimination and RNA splicing, and highlight the role that the variation in the population-genetic environment may play in shaping their target sequences. PMID- 26140479 TI - In Vivo Remote Control of Reactions in Caenorhabditis elegans by Using Supramolecular Nanohybrids of Carbon Nanotubes and Liposomes. AB - A supramolecular nanohybrid based on carbon nanotubes and liposomes that is highly biocompatible and capable of permeation through cells is described. The nanohybrid can be loaded with a variety of functional molecules and is structurally controlled by near-infrared laser irradiation for the release of molecules from the nanohybrids in a targeted manner via microscopy. We implemented the controlled release of molecules from the nanohybrids and demonstrated remote regulation of the photoinduced nanohybrid functions. As a proof of principle, nanohybrids loaded with amiloride were successfully used in the spatiotemporally targeted blocking of amiloride-sensitive mechanosensory neurons in living Caenorhabditis elegans. Our prototype could inspire new designs for biomimetic parasitism and symbiosis, and biologically active nanorobots for the higher-level manipulation of organisms. PMID- 26140478 TI - Intranuclear Actin Regulates Osteogenesis. AB - Depolymerization of the actin cytoskeleton induces nuclear trafficking of regulatory proteins and global effects on gene transcription. We here show that in mesenchymal stem cells (MSCs), cytochalasin D treatment causes rapid cofilin /importin-9-dependent transfer of G-actin into the nucleus. The continued presence of intranuclear actin, which forms rod-like structures that stain with phalloidin, is associated with induction of robust expression of the osteogenic genes osterix and osteocalcin in a Runx2-dependent manner, and leads to acquisition of osteogenic phenotype. Adipogenic differentiation also occurs, but to a lesser degree. Intranuclear actin leads to nuclear export of Yes-associated protein (YAP); maintenance of nuclear YAP inhibits Runx2 initiation of osteogenesis. Injection of cytochalasin into the tibial marrow space of live mice results in abundant bone formation within the space of 1 week. In sum, increased intranuclear actin forces MSC into osteogenic lineage through controlling Runx2 activity; this process may be useful for clinical objectives of forming bone. PMID- 26140480 TI - Reproducibility and interobserver variability of systolic blood flow velocity and 3D wall shear stress derived from 4D flow MRI in the healthy aorta. AB - PURPOSE: To investigate the reproducibility and interobserver variability of 3D aortic velocity vector fields and wall shear stress (WSS) averaged over five systolic timeframes derived from noncontrast 4D flow magnetic resonance imaging (MRI). MATERIALS AND METHODS: Fourteen controls underwent test-retest 4D flow MRI examinations separated by 16 +/- 3 days (resolution = 3.0-3.6 * 2.3-2.6 * 2.5-2.7 mm(3) ; TE/TR/FA = 2.5/4.9 msec/7 degrees ; Venc = 150 cm/s). Two observers segmented the aorta, and WSS was calculated for both series of scans and both segmentations. Test-retest and interobserver velocity and WSS vectors were compared on a voxel-by-voxel basis in the aorta and on a regional basis by subdividing the aortas in six segments. RESULTS: Test-retest: voxel-by-voxel Bland-Altman analysis revealed small differences (-0.03/-0.02 m/s/Pa), limits of agreement (LOA) of 0.25 m/s/0.29 Pa, and coefficients of variation (CV) of 20% for velocity/WSS. Voxel-by-voxel orthogonal regression analysis showed moderate agreement (slope: 1.14/1.16, intraclass correlation coefficient [ICC]: 0.76/0.67 for velocity/WSS). The regional analysis revealed a CV of 9%/8% and ICC of 0.9/0.9 for velocity/WSS. Interobserver: voxel-by-voxel difference for WSS was 0, LOA: 0.17/0.19 Pa, CV: 12/13%, slope: 1.01/1.09, ICC: 0.87/0.85 for test/retest. The CV/ICC for WSS in the regional analysis was 4%/1.0 for test and 3%/1.0 for retest. CONCLUSION: Systolic velocity and WSS derived from 4D flow MRI are reproducible between consecutive visits, with low interobserver variability in healthy volunteers. PMID- 26140481 TI - Intraoperative fiducial-less patient registration using volumetric 3D ultrasound: a prospective series of 32 neurosurgical cases. AB - OBJECT: Fiducial-based registration (FBR) is used widely for patient registration in image-guided neurosurgery. The authors of this study have developed an automatic fiducial-less registration (FLR) technique to find the patient-to-image transformation by directly registering 3D ultrasound (3DUS) with MR images without incorporating prior information. The purpose of the study was to evaluate the performance of the FLR technique when used prospectively in the operating room and to compare it with conventional FBR. METHODS: In 32 surgical patients who underwent conventional FBR, preoperative T1-weighted MR images (pMR) with attached fiducial markers were acquired prior to surgery. After craniotomy but before dural opening, a set of 3DUS images of the brain volume was acquired. A 2 step registration process was executed immediately after image acquisition: 1) the cortical surfaces from pMR and 3DUS were segmented, and a multistart sum-of squared-intensity-difference registration was executed to find an initial alignment between down-sampled binary pMR and 3DUS volumes; and 2) the alignment was further refined by a mutual information-based registration between full resolution grayscale pMR and 3DUS images, and a patient-to-image transformation was subsequently extracted. RESULTS: To assess the accuracy of the FLR technique, the following were quantified: 1) the fiducial distance error (FDE); and 2) the target registration error (TRE) at anterior commissure and posterior commissure locations; these were compared with conventional FBR. The results showed that although the average FDE (6.42 +/- 2.05 mm) was higher than the fiducial registration error (FRE) from FBR (3.42 +/- 1.37 mm), the overall TRE of FLR (2.51 +/- 0.93 mm) was lower than that of FBR (5.48 +/- 1.81 mm). The results agreed with the intent of the 2 registration techniques: FBR is designed to minimize the FRE, whereas FLR is designed to optimize feature alignment and hence minimize TRE. The overall computational cost of FLR was approximately 4-5 minutes and minimal user interaction was required. CONCLUSIONS: Because the FLR method directly registers 3DUS with MR by matching internal image features, it proved to be more accurate than FBR in terms of TRE in the 32 patients evaluated in this study. The overall efficiency of FLR in terms of the time and personnel involved is also improved relative to FBR in the operating room, and the method does not require additional image scans immediately prior to surgery. The performance of FLR and these results suggest potential for broad clinical application. PMID- 26140482 TI - Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases. AB - OBJECT: Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is a treatment option for patients with melanoma in whom brain metastases have developed. Very limited data are available on treating patients with >=5 lesions. The authors sought to determine the effectiveness of SRS in patients with >=5 melanoma brain metastases. METHODS: A retrospective analysis of metastatic melanoma treated with SRS in a single treatment session for >=5 lesions was performed. Magnetic resonance imaging studies were reviewed post-SRS to evaluate local control (LC). Disease progression on imaging was defined using the 2009 Response Evaluation Criteria in Solid Tumors (RECIST). Survival curves were calculated from the date of brain metastases diagnosis or the date of SRS by using the Kaplan-Meier (KM) method. Univariate and multivariate analysis (UVA and MVA, respectively) were performed using the Cox proportional-hazards model. RESULTS: The authors identified 149 metastatic brain lesions treated in 28 patients. The median patient age was 60.5 years (range 38-83 years), and the majority of patients (24 [85.7%]) had extracranial metastases. Four patients (14.3%) had received previous whole-brain radiotherapy (WBRT), and 11 (39.3%) had undergone previous SRS. The median planning target volume (PTV) was 0.34 cm3 (range 0.01-12.5 cm3). Median follow-up was 6.3 months (range 1-46 months). At the time of treatment, 7% of patients were categorized as recursive partitioning analysis (RPA) Class I, 89% as RPA Class II, and 4% as RPA Class III. The rate of local failure was 11.4%. Kaplan-Meier LC estimates at 6 and 12 months were 91.3% and 82.2%, respectively. A PTV volume>=0.34 cm3 was a significant predictor of local failure on UVA (HR 16.1, 95% CI 3.2-292.6, p<0.0001) and MVA (HR 14.8, 95% CI 3.0-268.5, p=0.0002). Sixteen patients (57.1%) were noted to have distant failure in the brain with a median time to failure of 3 months (range 1-15 months). Nine patients with distant failures received WBRT, and 7 received additional SRS. Median overall survival (OS) was 9.4 and 7.6 months from the date of brain metastases diagnosis and the date of SRS, respectively. The KM OS estimates at 6 and 12 months were 57.8% and 28.2%, respectively, from the time of SRS treatment. The RPA class was a significant predictor of KM OS estimates from the date of treatment (p=0.02). Patients who did not receive WBRT after SRS treatment had decreased OS on MVA (HR 3.5, 95% CI 1.1-12.0, p=0.03), and patients who did not receive WBRT prior to SRS had improved OS (HR 0.11, 95% CI 0.02-0.53, p=0.007). CONCLUSIONS: Stereotactic radiosurgery for >=5 lesions appears to be effective for selected patients with metastatic melanoma, offering excellent LC. This is particularly important for patients as new targeted systemic agents are improving outcomes but still have limited efficacy within the central nervous system. PMID- 26140483 TI - Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas. AB - OBJECT: Irreversible electroporation (IRE) is a novel nonthermal ablation technique that has been used for the treatment of solid cancers. However, it has not been evaluated for use in brain tumors. Here, the authors report on the safety and feasibility of using the NanoKnife IRE system for the treatment of spontaneous intracranial gliomas in dogs. METHODS: Client-owned dogs with a telencephalic glioma shown on MRI were eligible. Dog-specific treatment plans were generated by using MRI-based tissue segmentation, volumetric meshing, and finite element modeling. After biopsy confirmation of glioma, IRE treatment was delivered stereotactically with the NanoKnife system using pulse parameters and electrode configurations derived from therapeutic plans. The primary end point was an evaluation of safety over the 14 days immediately after treatment. Follow up was continued for 12 months or until death with serial physical, neurological, laboratory, and MRI examinations. RESULTS: Seven dogs with glioma were treated. The mean age of the dogs was 9.3 +/- 1.6 years, and the mean pretreatment tumor volume was 1.9 +/- 1.4 cm(3). The median preoperative Karnofsky Performance Scale score was 70 (range 30-75). Severe posttreatment toxicity was observed in 2 of the 7 dogs; one developed fatal (Grade 5) aspiration pneumonia, and the other developed treatment-associated cerebral edema, which resulted in transient neurological deterioration. Results of posttreatment diagnostic imaging, tumor biopsies, and neurological examinations indicated that tumor ablation was achieved without significant direct neurotoxicity in 6 of the 7 dogs. The median 14-day post-IRE Karnofsky Performance Scale score of the 6 dogs that survived to discharge was 80 (range 60-90), and this score was improved over the pretreatment value in every case. Objective tumor responses were seen in 4 (80%) of 5 dogs with quantifiable target lesions. The median survival was 119 days (range 1 to > 940 days). CONCLUSION: With the incorporation of additional therapeutic planning procedures, the NanoKnife system is a novel technology capable of controlled IRE ablation of telencephalic gliomas. PMID- 26140484 TI - The meningeal branches of the superior cerebellar artery: a surgical observation study. AB - OBJECT The tentorial branch of the posterior cerebral artery was first identified in a cadaver dissection study. However, the tentorial branch of the superior cerebellar artery (SCA) has not been clearly described in autopsy or normal anatomical studies. In this study, a dural branch of the SCA that was found during the surgical treatment of trigeminal neuralgia is described. METHODS Between April 2011 and March 2014, 70 patients with idiopathic trigeminal neuralgia underwent microvascular decompression. The records of 58 patients were reviewed to investigate the meningeal branch of the SCA. RESULTS The meningeal branch of the SCA was visualized in 15 of the 58 patients (25.9%). In 4 patients, it was necessary to divide this branch in order to achieve decompression of the trigeminal nerve without eliciting postoperative neurological deficits. CONCLUSIONS This is the first identification of the meningeal branch of the SCA in living subjects, and such branches were rather frequently found. Recognition of this branch is important for the management of lesions in the cerebellopontine angle and tentorial lesions, using either an open microsurgical or endovascular method. PMID- 26140485 TI - Peritumoral cysts associated with pituitary macroadenoma. AB - OBJECT: Peritumoral cysts are benign nonneoplastic cysts that are found adjacent to extraaxial brain tumors such as meningiomas, schwannomas, craniopharyngiomas, and esthesioneuroblastomas. Peritumoral cysts associated with pituitary macroadenomas have not been previously described in the literature. The authors report 6 cases of giant macroadenoma-associated peritumoral cysts and delineate their imaging spectrum. METHODS: The authors retrospectively reviewed the records of 179 patients diagnosed with pituitary macroadenomas who underwent tumor resection at their institution and had preoperative MRI scans available for review. The patients were evaluated for the presence of associated peritumoral cysts. Clinical presentation, histopathology, follow-up time, tumor and peritumoral cyst dimensions were recorded. Signal intensity on T1-weighted, T2 weighted, diffusion-weighted, and FLAIR sequences, as well as pre- and postcontrast appearance, were determined. RESULTS: Six patients (3.4%) with associated peritumoral cysts were identified in our cohort of 179 patients with pituitary macroadenoma. Twelve patients in the cohort had giant macroadenomas (>= 4.0 cm), and 50% of these tumors had associated peritumoral cysts with significant extrasellar extension of the macroadenoma. Only tumors with craniocaudal, transverse, and anteroposterior diameters of 3.6 * 3.4 * 4.2 cm to 7.0 * 7.4 * 6.8 cm (mean 5.3 * 5.1 * 5.6 cm), respectively, had associated peritumoral cysts. The growth pattern in all tumors was suprasellar, with predominant anterior and lateral extension. Cysts showed T1-weighted, T2 weighted, and FLAIR hyperintensity in 67%, 67%, and 60% of patients, respectively. There was no contrast enhancement of the cyst wall or fluid contents in any patient. Postoperatively, cysts had completely resolved (4 of 5) or significantly decreased in size (1 of 5). One patient was lost to follow-up. CONCLUSIONS: Macroadenoma-associated peritumoral cysts are rare, benign, and likely nonneoplastic fluid collections that do not represent neoplasm. These cysts display a predictable pattern of hyperintensity on T1-weighted, T2 weighted, and FLAIR sequences and do not enhance. They most likely represent proteinaceous CSF in a sulcus or cistern that becomes trapped (encysted) by anterolateral extension of unusually large macroadenomas. Peritumoral cysts may facilitate resection of the associated macroadenoma by providing a cleavage plane. PMID- 26140486 TI - Intrathecal preservative-free normal saline challenge magnetic resonance myelography for the identification of cerebrospinal fluid leaks in spontaneous intracranial hypotension. AB - OBJECT: A CSF leak can be difficult to locate in patients who present with spontaneous intracranial hypotension (SIH). The purpose of this case series was to describe the authors' experience with intrathecal preservative-free normal saline challenge coupled with contrast-enhanced MR myelography (CEMRM), which was used to provoke and detect a CSF leakage site in patients with SIH. METHODS: The authors performed a retrospective review of the records of patients who underwent preservative-free normal saline challenge followed by intrathecal gadolinium (Gd) contrast infusion and MR myelography from 2010 to 2012. RESULTS: The records survey identified 5 patients who underwent 6 procedures. Intrathecal preservative free normal saline challenge followed by CEMRM identified a CSF leak during 5 of the 6 procedures. Previous CT myelograms were available from 4 patients, which did not reveal a leakage site. A CT myelogram of 1 patient showed a single leak, but the authors' saline challenge-CEMRM technique identified multiple additional leakage sites. Three patients exhibited transient postprocedural symptoms related to the saline infusion, but no long-term or permanent adverse effects related to the procedure were observed. CONCLUSIONS: Instillation of preservative-free normal saline into the thecal sac followed by intrathecal Gd infusion is a safe technique that may increase the detection of a CSF leak on MR myelography images in patients with SIH. PMID- 26140487 TI - Spontaneous retroclival hematoma in pituitary apoplexy: case series. AB - OBJECT: Pituitary apoplexy is a rare and potentially life-threatening disorder that is most commonly characterized by a combination of sudden headache, visual disturbance, and hypothalamic/hormonal dysfunction. In many cases, there is hemorrhagic infarction of an underlying pituitary adenoma. The resulting clinical symptoms are due to compression of the remaining pituitary, cavernous sinuses, or cranial nerves. However, there are only 2 case reports in the literature describing spontaneous retroclival expansion of hemorrhage secondary to pituitary apoplexy. Ten cases of this entity with a review of the literature are presented here. METHODS: This is a single-institution retrospective review of 2598 patients with sellar and parasellar masses during the 10-year period between 1999 and 2009. The pituitary and brain MRI and MRI studies were reviewed by 2 neuroradiologists for evidence of apoplexy, with particular attention given to retroclival extension. RESULTS: Eighteen patients (13 men and 5 women; mean age 54 years) were identified with presenting symptoms of sudden onset of headache and ophthalmoplegia, and laboratory findings consistent with pituitary apoplexy. Ten of these patients (8 men and 2 women; mean age 55 years) had imaging findings consistent with retroclival hematoma. CONCLUSIONS: Retroclival hemorrhage was seen in the majority of cases of pituitary apoplexy (56%), suggesting that it is more common than previously thought. PMID- 26140488 TI - Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas. AB - OBJECT: In this paper, the authors' aim was to determine short-term volumetric and diametric tumor growth and identify clinical, radiological, and dosimetric predictors of adverse radiation events (AREs) following stereotactic radiosurgery (SRS) for intracranial WHO Grade I meningiomas. METHODS: This is a retrospective review of all WHO Grade I meningiomas that were treated with SRS (primary or adjuvant) between December 2005 and June 2012 at the University Health Network. Seventy-five patients had at least 24 months of both clinical and radiological follow-up and were, therefore, included in this study. Tumor growth was defined as any volumetric or diametric change greater than 10% per year. Any variation less than +10% was considered growth stability. Volumetric measurements were made using T1-weighted gadolinium-enhanced 3-T MRI scans and ITK-SNAP software. Tumor growth rates were calculated using the specific growth rate (SGR). Univariate statistics were used to identify predictors of post-SRS AREs. All statistical analyses were performed using IBM SPSS. RESULTS: Women accounted for 69.3% of patients, and the mean treatment age was 58.6 years. Median follow-up was 36.2 months. Twenty-one (28%) patients had undergone prior resection. Two (3%) patients required salvage surgical intervention following SRS. The majority of the lesions (56%) were skull base tumors. Median tumor volume and diameter were 5.2 cm3 and 27.5 mm, respectively. The absence of tumor growth was observed in 39 cases (52%) based on the volumetric measurements, while the absence of tumor growth was observed in 69 cases (92%) based on the diametric measurements. Twenty six patients (34.6%) experienced new-onset AREs, including headache (17.3%), cranial neuropathy (10.6%), speech impairment (2.7%), tremors (2.7%), and ataxia (1.3%). Fourteen patients (18.7%) experienced new-onset edema, and 4 of these patients were symptomatic. A lower conformity index (1.24 vs 1.4) was significantly associated with the development of edema (p<0.001 power>0.8). Patients with meningiomas that had growth rates of more than 10% per year were more likely to experience long-term headaches after SRS (p=0.022). CONCLUSIONS: Volume-based reporting of SRS outcomes for meningiomas may be a more accurate method given the complex morphology of some lesions. The conformity index was identified as a predictor of edema following radiosurgery. PMID- 26140490 TI - Letter to the Editor: Optic radiations and anterior commissure. PMID- 26140489 TI - Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery. AB - OBJECT: Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)-induced PpIX fluorescence in a series of patients with LGG. METHODS: Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 mg/kg of ALA approximately 3 hours prior to surgery under an institutional review board-approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS: Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score >= 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 MUg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively. CONCLUSIONS: The authors' initial experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However, the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs, and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed, at least in the authors' initial experience reported here, if quantitative detection methods are deployed, the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches the accuracy associated with visual fluorescence in HGGs. PMID- 26140491 TI - Letter to the Editor: The transbasal approach: historical observation. PMID- 26140492 TI - "Live cadavers" for training in the management of intraoperative aneurysmal rupture. AB - OBJECT: Intraoperative rupture occurs in approximately 9.2% of all cranial aneurysm surgeries. This event is not merely a surgical complication, it is also a real surgical crisis that requires swift and decisive action. Neurosurgical residents may have little exposure to this event, but they may face it in their practice. Laboratory training would be invaluable for developing competency in addressing this crisis. In this study, the authors present the "live cadaver" model, which allows repetitive training under lifelike conditions for residents and other trainees to practice managing this crisis. METHODS: The authors have used the live cadaver model in 13 training courses from 2009 to 2014 to train residents and neurosurgeons in the management of intraoperative aneurysmal rupture. Twenty-three cadaveric head specimens harboring 57 artificial and 2 real aneurysms were used in these courses. Specimens were specially prepared for this technique and connected to a pump that sent artificial blood into the vessels. This setting created a lifelike situation in the cadaver that simulates live surgery in terms of bleeding, pulsation, and softness of tissue. RESULTS: A total of 203 neurosurgical residents and 89 neurosurgeons and faculty members have practiced and experienced the live cadaver model. Clipping of the aneurysm and management of an intraoperative rupture was first demonstrated by an instructor. Then, trainees worked for 20- to 30-minute sessions each, during which they practiced clipping and reconstruction techniques and managed intraoperative ruptures. Ninety-one of the participants (27 faculty members and 64 participants) completed a questionnaire to rate their personal experience with the model. Most either agreed or strongly agreed that the model was a valid simulation of the conditions of live surgery on cerebral aneurysms and represents a realistic simulation of aneurysmal clipping and intraoperative rupture. Actual performance improvement with this model will require detailed measurement for validating its effectiveness. The model lends itself to evaluation using precise performance measurements. CONCLUSIONS: The live cadaver model presents a useful simulation of the conditions of live surgery for clipping cerebral aneurysms and managing intraoperative rupture. This model provides a means of practice and promotes team management of intraoperative cerebrovascular critical events. Precise metric measurement for evaluation of training performance improvement can be applied. PMID- 26140493 TI - Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy. AB - OBJECT: The aim in this study was to present long-term results regarding overall survival (OS), adverse effects, and toxicity following fractionated intracavitary radioimmunotherapy (RIT) with iodine-131- or yttrium-90-labeled anti-tenascin monoclonal antibody ((131)I-mAB or (90)Y-mAB) for the treatment of patients with malignant glioma. METHODS: In 55 patients (15 patients with WHO Grade III anaplastic astrocytoma [AA] and 40 patients with WHO Grade IV glioblastoma multiforme [GBM]) following tumor resection and conventional radiotherapy, radioimmunoconjugate was introduced into the postoperative resection cavity. Patients received 5 cycles of (90)Y-mAB (Group A, average dose 18 mCi/cycle), 5 cycles of (131)I-mAB (Group B, average dose 30 mCi/cycle), or 3 cycles of (131)I mAB (Group C, 50, 40, and 30 mCi). RESULTS: Median OS of patients with AA was 77.2 months (95% CI 30.8 to > 120). Five AA patients (33%) are currently alive, with a median observation time of 162.2 months. Median OS of all 40 patients with GBM was 18.9 months (95% CI 15.8-25.3), and median OS was 25.3 months (95% CI18 30) forthose patients treated with the (131)I-mAB. Three GBM patients are currently alive. One-, 2-, and 3-year survival probabilities were 100%, 93.3%, and 66.7%, respectively, for AA patients and 82.5%, 42.5%, and 15.9%, respectively, for GBM patients. Restratification of GBM patients by recursive partitioning analysis (RPA) Classes III, IV, and V produced median OSs of 31.1, 18.9, and 14.5 months, respectively (p = 0.004), which was higher than expected. Multivariate analysis confirmed the role of RPA class, age, and treatment in predicting survival. No Grade 3 or 4 hematological, nephrologic, or hepatic toxic effects were observed; 4 patients developed Grade 3 neurological deficits. Radiological signs of radionecrosis were observed in 6 patients, who were all responding well to steroids. CONCLUSIONS: Median OS of GBM and AA patients treated with (131)I-mABs reached 25.3 and 77.2 months, respectively, thus markedly exceeding that of historical controls. Adverse events remained well controllable with the fractionated dosage regimen. PMID- 26140494 TI - Operative wound-related complications after cranial revascularization surgeries. AB - OBJECT: Intracranial revascularization surgeries are an effective treatment for moyamoya disease and other intracranial vascular obliterative diseases. However, in some cases, wound-related complications develop after surgery. Although the incidence of wound complication is supposed to be higher than that with a usual craniotomy, this complication has rarely been the focus of studies in the literature that report the outcomes of revascularization surgeries. Here, the relationship between intracranial revascularization surgeries and their complications is statistically assessed. METHODS: Between October 2004 and February 2010, 71 patients were treated using cerebral revascularization surgeries on 98 sides of the head. The relationship between wound complications and operative technique was retrospectively assessed. Multivariate logistic regression analysis was performed to identify the risk factors of wound complication, including operative technique, age, sex, diabetes mellitus (DM), hypertension, hyperlipidemia, and smoking history. RESULTS: In total, there were 21 (21.4%) operative wound complications. Of these 21 complications, there were 14 (66.7%) minor complications and 7 (33.3%) major complications. No statistically significant relationship was found between wound complications and any surgical procedure. A trend toward severer complications was demonstrated for the procedures that used both STA branches ("double" procedures) in comparison with the procedures that used only 1 STA branch ("single" procedures, p=0.016, Cochran-Armitage trend test). Multivariate logistic regression analysis also revealed that double procedures demonstrated a significantly higher incidence of wound complications than single procedures (OR 3.087, p=0.048). DM was found to be a risk factor for wound complication (OR 9.42, p=0.02), but age, sex, hypertension, and hyperlipidemia were not associated with the incidence of complications. Even though the blood supply to the scalp is abundant due to 5 arteriovenous systems, sometimes cutaneous necrosis develops after intracranial revascularization surgeries. The galeal blood supply is thought to be crucial for preventing wound-related complications. Special care is also thought to be required for DM patients. CONCLUSIONS: Revascularization surgeries seemed to demonstrate a higher risk of wound-related complications. Double-type procedures, which use both branches of the STA, and a history of DM were found to be risk factors for wound-related complications. Attention should be paid to the design of the galeal incision and vessel harvest line. Also, special attention should be paid to patients with DM. PMID- 26140495 TI - Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm. AB - OBJECT Large arteriovenous malformations (AVMs) remain difficult to treat, and ideal treatment parameters for volume-staged stereotactic radiosurgery (VS-SRS) are still unknown. The object of this study was to compare VS-SRS treatment outcomes for AVMs larger than 10 ml during 2 eras; Era 1 was 1992-March 2004, and Era 2 was May 2004-2008. In Era 2 the authors prospectively decreased the AVM treatment volume, increased the radiation dose per stage, and shortened the interval between stages. METHODS All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed. RESULTS Of 69 patients intended for VS-SRS, 63 completed all stages. The median patient age at the first stage of VS-SRS was 34 years (range 9-68 years). The median modified radiosurgery based AVM score (mRBAS), total AVM volume, and volume per stage in Era 1 versus Era 2 were 3.6 versus 2.7, 27.3 ml versus 18.9 ml, and 15.0 ml versus 6.8 ml, respectively. The median radiation dose per stage was 15.5 Gy in Era 1 and 17.0 Gy in Era 2, and the median clinical follow-up period in living patients was 8.6 years in Era 1 and 4.8 years in Era 2. All outcomes were measured from the first stage of VS-SRS. Near or complete obliteration was more common in Era 2 (log-rank test, p = 0.0003), with 3- and 5-year probabilities of 5% and 21%, respectively, in Era 1 compared with 24% and 68% in Era 2. Radiosurgical dose, AVM volume per stage, total AVM volume, era, compact nidus, Spetzler-Martin grade, and mRBAS were significantly associated with near or complete obliteration on univariate analysis. Dose was a strong predictor of response (Cox proportional hazards, p < 0.001, HR 6.99), with 3- and 5-year probabilities of near or complete obliteration of 5% and 16%, respectively, at a dose < 17 Gy versus 23% and 74% at a dose >= 17 Gy. Dose per stage, compact nidus, and total AVM volume remained significant predictors of near or complete obliteration on multivariate analysis. Seventeen patients (25%) had salvage surgery, SRS, and/or embolization. Allowing for salvage therapy, the probability of cure was more common in Era 2 (log-rank test, p = 0.0007) with 5-year probabilities of 0% in Era 1 versus 41% in Era 2. The strong trend toward improved cure in Era 2 persisted on multivariate analysis even when considering mRBAS (Cox proportional hazards, p = 0.055, HR 4.01, 95% CI 0.97-16.59). The complication rate was 29% in Era 1 compared with 13% in Era 2 (Cox proportional hazards, not significant). CONCLUSIONS VS-SRS is an option to obliterate or downsize large AVMs. Decreasing the AVM treatment volume per stage to <= 8 ml with this technique allowed a higher dose per fraction and decreased time to response, as well as improved rates of near obliteration and cure without increasing complications. Reducing the volume of these very large lesions can facilitate a surgical approach for cure. PMID- 26140496 TI - Disrupting the right pars opercularis with electrical stimulation frees the song: case report. AB - The authors report the first case of a strikingly unusual speech impairment evoked by intraoperative electrostimulation in a 36-year-old right-handed patient, a well-trained singer, who underwent awake surgery for a right fronto temporo-insular low-grade glioma. Functionally disrupting the pars opercularis of the right inferior frontal gyrus led the patient to automatically switch from a speaking to a singing mode of language production. Given the central role of the right pars opercularis in the inhibitory control network, the authors propose that this finding may be interpreted as possible evidence for a competitive and independent neurocognitive subnetwork devoted to the melodically intoned articulation of words (normal language-based vs singing-based) in subjects with high expertise. From a more clinical perspective, such data may have implications for awake neurosurgery, especially to preserve the quality of life for singers. PMID- 26140497 TI - Chimeric groin free flaps: Design and clinical application. AB - BACKGROUND: Reconstruction of composite extremity defects or through-and-through oral defects remains challenging for surgeons. Chimeric flaps are ideal for repairing these lesions. In this article, we report the design of various chimeric groin free flaps for the reconstruction of both complex oral and extremity defects in 18 patients. METHODS: Between 2010 and 2014, 18 patients with composite tissue defect or two defects in the extremities or head and neck region, underwent reconstruction with cutaneous-cutaneous, musculo-cutaneous, or osteo-cutaneous chimeric groin free flaps. The size and pedicles length of the chimeric groin flaps based on the superficial circumflex iliac artery (SCIA) were tailored to the lesions. Patient-reported post-operative outcomes at the out patient department were evaluated. RESULTS: The types of chimeric groin free flaps included cutaneous-cutaneous (n = 12), musculo-cutaneous (n = 1), and osteo cutaneous (n = 5) flaps. Three to four SCIA branches (mean: 3.33) could be used for flap design. The cutaneous flap size ranged from 1.5 cm * 6 cm to 11 cm * 30 cm, and the bone flap size ranged from 1 cm * 1.5 cm to 2.5 cm * 6 cm. All flaps survived, and no significant complications developed at recipient or donor sites. Functional recovery after reconstruction was satisfactory in most patients after a mean of 17.27 months (ranging 2-42 months) of follow-up. CONCLUSION: The innovative flap technique presented herein has advantages including greater reliability, as well as the ability to tailor the dimensions and flap paddles to specific lesions and reconstruct two defects or one composite defect using only one (chimeric) flap. PMID- 26140498 TI - P-C-Activated Bimetallic Rhodium Xantphos Complexes: Formation and Catalytic Dehydrocoupling of Amine-Boranes. AB - {Rh(xantphos)}-based phosphido dimers form by P-C activation of xantphos (4,5 bis(diphenylphosphino)-9,9-dimethylxanthene) in the presence of amine-boranes. These dimers are active dehydrocoupling catalysts, forming polymeric [H2 BNMeH]n from H3 B?NMeH2 and dimeric [H2 BNMe2 ]2 from H3 B?NMe2 H at low catalyst loadings (0.1 mol %). Mechanistic investigations support a dimeric active species, suggesting that bimetallic catalysis may be possible in amine-borane dehydropolymerization. PMID- 26140499 TI - Quantum Optical Signature of Plasmonically Coupled Nanocrystal Quantum Dots. AB - Small clusters of two to three silica-coated nanocrystals coupled to plasmonic gap-bar antennas can exhibit photon antibunching, a characteristic of single quantum emitters. Through a detailed analysis of their photoluminescence emissions characteristics, it is shown that the observed photon antibunching is the evidence of coupled quantum dot formation resulting from the plasmonic enhancement of dipole-dipole interaction. PMID- 26140500 TI - A preliminary randomized trial of the mechanical insufflator-exsufflator versus breath-stacking technique in patients with amyotrophic lateral sclerosis. AB - A major problem faced by patients with amyotrophic lateral sclerosis (ALS) in respiratory failure is the inability to cough effectively. Forty eligible ALS patients were randomized to the breath-stacking technique using a lung volume recruitment bag (n = 21) or mechanical insufflator-exsufflator MI-E (n = 19) and followed up at three-monthly intervals for at least 12 months or until death. Results showed that there were 13 episodes of chest infection in the breath stacking group and 19 episodes in the MI-E group (p = 0.92), requiring 90 and 95 days of antibiotics, respectively (p = 0.34). The mean duration of symptoms per chest infection was 6.9 days in the breath-stacking group and 3.9 days in MI-E group (p = 0.16). There were six episodes of hospitalization in each group (p = 0.64). The chance of hospitalization, in the event of a chest infection, was 0.46 in the breath-stacking group and 0.31 in MI-E group (p = 0.47). Median survival in the breath-stacking group was 535 days and 266 days in the MI-E group (p = 0.34). The QoL was maintained above 75% of baseline for a median of 329 days in the breath-stacking group and 205 days in the MI-E group (p = 0.41). In conclusion, lack of statistically significant differences due to sub-optimal power and confounders precludes a definitive conclusion with respect to the relative efficacy of one cough augmentation technique over the other. This study however, provides useful lessons and informative data, needed to strengthen the power calculation, inclusion criteria and randomization factors for a large scale definitive trial. Until such a definitive trial can be undertaken, we recommend the breath-stacking technique as a low-cost, first-line intervention for volume recruitment and cough augmentation in patients with ALS who meet the criteria for intervention with non-invasive ventilation. PMID- 26140501 TI - Validation of a sensitive HPLC/fluorescence method for assessment of ciprofloxacin levels in plasma and prostate microdialysate samples from rats. AB - Chronic bacterial prostatitis treatment consists of broad-spectrum antibiotic therapy for long periods of time. Drug penetration into the prostate makes the treatment a challenged. Ciprofloxacin is one of the most prescribed drugs for this treatment. A liquid chromatography with fluorescence detection method was developed and validated for determining ciprofloxacin concentrations in two different matrices: plasma and prostate microdialysate. Ciprofloxacin was separated on a C18 column eluted with a mobile phase constituted of a mixture of 0.4% aqueous triethylamine:methanol:acetonitrile (75:15:10, v/v/v) and 0.4% aqueous triethylamine:acetonitrile (88:12, v/v) for microdialysate and plasma samples, respectively. Linearity was obtained over a concentration range of 5 1000 ng/mL (microdialysate) and 10-2000 ng/mL (plasma), with coefficients of determination >=0.9956. Precision was determined from the analysis of six quality control samples and showed RSD values <11.1 and 7.4% for intra and inter-assay precision, respectively. The accuracy ranged from 85.6 to 114.3%. The method was applied to a preliminary pharmacokinetic study to investigate ciprofloxacin concentrations in prostate, sampled by microdialysis, and plasma after a 7 mg/kg intravenous dose to Wistar rats. The method showed high sensitivity using only protein precipitation as plasma sample clean-up and was successfully applied to investigate ciprofloxacin prostate penetration. PMID- 26140502 TI - Health utility outcomes in patients undergoing medical management for chronic rhinosinusitis: a prospective multiinstitutional study. AB - BACKGROUND: A health utility value represents an individual's preference for living in a specific health state and is used in cost-utility analyses. This study investigates the impact of continuing medical therapy on health utility outcomes in patients with chronic rhinosinusitis (CRS). METHODS: The Medical Outcomes Study Short Form-6D (SF-6D) questionnaire was administered to patients prospectively enrolled in a longitudinal study examining treatment outcomes for CRS. Patients were prescribed robust, initial medical therapy and then elected to continue with medical therapy (n = 40) or undergo endoscopic sinus surgery (ESS), followed by medical therapy (n = 152). Patients observed through treatment crossover to ESS were also evaluated (n = 20). Health utility values (SF-6D) were generated at baseline, 6-months, and 12-months follow-up for both cohorts and evaluated using repeated measures analysis of variance (ANOVA). RESULTS: Treatment crossover patients were found to have a significantly higher prevalence of previous sinus surgery compared to medical management (chi(2) = 6.91; p = 0.009) and surgical intervention (chi(2) = 8.11; p = 0.004) subgroups. Mean baseline utility value for the medical therapy cohort was significantly better compared to the ESS cohort (mean +/- standard deviation; 0.76 +/- 0.12 vs 0.70 +/ 0.15; p = 0.023). Significant improvement in health utility was reported in the ESS cohort (F(2) = 37.69; p < 0.001), whereas values remained stable, without significant improvement, in both the medical therapy cohort (F(2) = 0.03; p = 0.967) and treatment crossover cohort (F(2) = 2.36; p = 0.115). CONCLUSION: Patients electing continued medical management report better baseline health utility compared to patients electing ESS. Patients electing ESS show significant improvement in health utility, whereas those electing continued medical management demonstrate stable health utility over 12 months. PMID- 26140503 TI - Rotaxanes Capped with Host Molecules: Supramolecular Behavior of Adamantylated Bisimidazolium Salts Containing a Biphenyl Centerpiece. AB - Bisimidazolium salts with one central biphenyl binding site and two terminal adamantyl binding sites form water-soluble binary or ternary aggregates with cucurbit[7]uril (CB7) and beta-cyclodextrin (beta-CD) with rotaxane and pseudorotaxane architectures. The observed arrangements result from cooperation of the supramolecular stopper binding strength and steric barriers against free slippage of the CB7 and beta-CD host molecules over the bisimidazolium guest axle. PMID- 26140504 TI - Reverse retrospective motion correction. AB - PURPOSE: One potential barrier for using prospective motion correction (PMC) in the clinic is the unpredictable nature of a scan because of the direct interference with the imaging sequence. We demonstrate that a second set of "de corrected" images can be reconstructed from a scan with PMC that show how images would have appeared without PMC enabled. THEORY AND METHODS: For three dimensional scans, the effects of PMC can be undone by performing a retrospective reconstruction based on the inverse of the transformation matrix used for real time gradient feedback. Retrospective reconstruction is performed using a generalized SENSE approach with continuous head motion monitored using a single marker optical camera system. RESULTS: Reverse retrospective reconstruction is demonstrated for phantom and in vivo scans using an magnetization-prepared rapid gradient echo (MPRAGE) sequence including parallel and Partial Fourier acceleration. CONCLUSION: Reverse retrospective reconstruction can almost perfectly undo the effects of prospective feedback, and thereby provide a second image data set with the effects of motion correction removed. In case of correct feedback, one can directly compare the quality of the corrected with that of the uncorrected scan. Additionally, because erroneous feedback during PMC may introduce artifacts, it is possible to eliminate artifacts in a corrupted scan by reversing the false gradient updates. Magn Reson Med 75:2341-2349, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26140506 TI - Direct comparison of the performance of a bio-inspired synthetic nickel catalyst and a [NiFe]-hydrogenase, both covalently attached to electrodes. AB - The active site of hydrogenases has been a source of inspiration for the development of molecular catalysts. However, direct comparisons between molecular catalysts and enzymes have not been possible because different techniques are used to evaluate both types of catalysts, minimizing our ability to determine how far we have come in mimicking the enzymatic performance. The catalytic properties of the [Ni(P(Cy) 2 N(Gly) 2 )2 ](2+) complex with the [NiFe]-hydrogenase from Desulfovibrio vulgaris immobilized on a functionalized electrode were compared under identical conditions. At pH 7, the enzyme shows higher activity and lower overpotential with better stability, while at low pH, the molecular catalyst outperforms the enzyme in all respects. This is the first direct comparison of enzymes and molecular complexes, enabling a unique understanding of the benefits and detriments of both systems, and advancing our understanding of the utilization of these bio-inspired complexes in fuel cells. PMID- 26140505 TI - Advances in genetic therapeutic strategies for Duchenne muscular dystrophy. AB - NEW FINDINGS: What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches. Duchenne muscular dystrophy is a lethal X-linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene-replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re-establish muscle function. PMID- 26140507 TI - Shape-Controlled Growth of Carbon Nanostructures: Yield and Mechanism. AB - Carbon nanostructures with precisely controlled shapes are difficult materials to synthesize. A facet-selective-catalytic process was thus proposed to synthesize polymer-linked carbon nanostructures with different shapes, covering straight carbon nanofiber, carbon nano Y-junction, carbon nano-hexapus, and carbon nano octopus. A thermal chemical vapor deposition process was applied to grow these multi-branched carbon nanostructures at temperatures lower than 350 degrees C. Cu nanoparticles were utilized as the catalyst and acetylene as the reaction gas. The growth of those multi-branched nanostructures was realized through the selective growth of polymer-like sheets on certain indexed facets of Cu catalyst. The vapor-facet-solid (VFS) mechanism, a new growth mode, has been proposed to interpret such a growth in the steps of formation, diffusion, and coupling of carbon-containing oligomers, as well as their final precipitation to form nanostructures on the selective Cu facets. PMID- 26140509 TI - Ligand-Free Pd-Catalyzed Double Carbonylation of Aryl Iodides with Amines to alpha-Ketoamides under Atmospheric Pressure of Carbon Monoxide and at Room Temperature. AB - A general Pd-catalyzed double carbonylation of aryl iodides with secondary or primary amines to produce alpha-ketoamides at atmospheric CO pressure has been developed. This transformation proceeds successfully even at room temperature and in the absence of any ligand and additive. A wide range of aryl iodides and amines can be coupled to the desired alpha-ketoamides in high yields with excellent chemoselectivities. Importantly, the current methodology has been demonstrated to be applied in the synthesis of bioactive molecules and chiral alpha-ketoamides. PMID- 26140510 TI - [Thought experiments, counterfactuality and self-understanding of the sciences around 1900]. PMID- 26140511 TI - [Investigation of Empiricism. On Ernst Mach's Conception of the Thought Experiment]. AB - Investigation of Empiricism. On Ernst Mach's Conception of the Thought Experiment. The paper argues that Ernst Mach's conception of the thought experiment from 1897/1905 holds a singular position in the lively discussions and repeated theorizations that have continued up to the present in relation to this procedure. Mach derives the thought experiment from scientific practice, and does not oppose it to the physical experiment, but, on the contrary, endows it with a robust relation to the facts. For Mach, the thought experiment is a reliable means of determining empiricism, and at the same time a real, because open and unbiased, experimenting. To shed light on this approach, the paper carries out a close reading of the relevant texts in Mach's body of writings (in their different stages of revision) and proceeds in three steps: first, Mach's processual understanding of science will be presented, which also characterizes his research and publication practice (I. 'Apercu' and 'Sketch'. Science as Process and Projection); then in a second step the physiological and biological justification and valorization of memory and association will be examined with which Mach limits the relevance of categories such as consciousness and will (II. The Biology of Consciousness. Or The Polyp Colony); against this background, thirdly, the specific empiricism can be revealed that Mach inscribes into the thought experiment by on the one hand founding it in the memory and association, and on the other by tracing it back to geometry, which he deploys as an experimenting oriented to experience (III. Thinking and Experience. The Thought Experiment). PMID- 26140512 TI - [Is it Possible to Experiment with Thought? Ernst Mach's Notion of Thought Experiment and its Pedagogical Context around 1900. ]. AB - Is it Possible to Experiment with Thought? Ernst Mach's Notion of Thought Experiment and its Pedagogical Context around 1900. The article tries to establish the crucial importance of the pedagogical dimension of Ernst Mach's ideas on experimenting with thought. The focus on contemporary pedagogics demonstrates, first, that Mach's didactic approach to physics is part of a much broader stream of pedagogical writings that transcends national and disciplinary borders and comprises a diversity of authors, e.g. Wilhelm Jerusalem, William James or Alfred N. Whitehead; second, that the much-heralded controversy between Mach and the French philosopher of science Pierre Duhem about thought experiments does not only revolve around epistemological issues but rather stems from their antagonist vision of teaching physics; and finally, third, that G. Stanley Hall's psychogenetic theory of pedagogics bears a strong resemblance with the evolutionary naturalism of Machian epistemology and helps explaining key tenets of Mach's conception of thought experiment. By establishing a broad convergence between the work of all these authors despite their different academic upbringing, background and nationality the article argues for a complex and historically fine-grained vision of the relations between natural, social and human sciences going beyond dichotomies like 'Erklaren' and 'Verstehen' or the 'Two Cultures'. PMID- 26140508 TI - Post-translational modifications of the cardiac proteome in diabetes and heart failure. AB - Cardiovascular complications are the leading cause of death in diabetic patients. Decades of research has focused on altered gene expression, altered cellular signaling, and altered metabolism. This work has led to better understanding of disease progression and treatments aimed at reversing or stopping this deadly process. However, one of the pieces needed to complete the puzzle and bridge the gap between altered gene expression and changes in signaling/metabolism is the proteome and its host of modifications. Defining the mechanisms of regulation includes examining protein levels, localization, and activity of the functional component of cellular machinery. Excess or misutilization of nutrients in obesity and diabetes may lead to PTMs contributing to cardiovascular disease progression. PTMs link regulation of metabolic changes in the healthy and diseased heart with regulation of gene expression itself (e.g. epigenetics), protein enzymatic activity (e.g. mitochondrial oxidative capacity), and function (e.g. contractile machinery). Although a number of PTMs are involved in each of these pathways, we will highlight the role of the serine and threonine O-linked addition of beta-N acetyl-glucosamine or O-GlcNAcylation. This nexus of nutrient supply, utilization, and storage allows for the modification and translation of mitochondrial function to many other aspects of the cell. PMID- 26140513 TI - [Thought Experiments of Economic Surplus: Science and Economy in Ernst Mach's Epistemology]. AB - Thought Experiments of Economic Surplus: Science and Economy in Ernst Mach's Epistemology. Thought experiments are an important element in Ernst Mach's epistemology: They facilitate amplifying our knowledge by experimenting with thoughts; they thus exceed the empirical experience and suspend the quest for immediate utility. In an economical perspective, Mach suggested that thought experiments depended on the production of an economic surplus based on the division of labor relieving the struggle for survival of the individual. Thus, as frequently emphasized, in Mach's epistemology, not only the 'economy of thought' is an important feature; instead, also the socioeconomic conditions of science play a decisive role. The paper discusses the mental and social economic aspects of experimental thinking in Mach's epistemology and examines those within the contemporary evolutionary, physiological, and economic contexts. PMID- 26140514 TI - [Thought Experiments in Historiographic Function: Max Weber on Eduard Meyer and the Question of Counterfactuality]. AB - Thought Experiments in Historiographic Function: Max Weber on Eduard Meyer and the Question of Counterfactuality. Max Weber's remarks on his colleague Eduard Meyer regarding counterfactual reasoning in history reflects a significant shift during the Methodenstreit around 1900. The question of attributing historical change strictly to either individual causes or abstract general laws has been tackled in a new way: By counterfactual reasoning a historian should be able to detect the most significant (and therefore meaningful) cause, event, or action for a certain historical outcome. Following Fritz Ringer, this paper argues that given the predominating methods of the natural sciences, scholars of the humanities conducted historical research by counterfactual thought experiments. This way, Weber pried open contemporary narratives (e.g. historicism), and by employing a unique historical causal analysis he made way for refined concepts to offer a model of interpretation that gave hope for a more feasible, practice oriented approach to historical research than the epistemological discussions had hitherto offered. PMID- 26140515 TI - Fabrication of Epoxy Vesicles using Self-Assembling Polystyrene-Montmorillonite Nanocomposite Reusable Template. AB - We report the fabrication of thermoset vesicles using a thermoplastic-clay nanocomposite vesicle reusable template. Epoxy polymer vesicles (EPV) of micrometer diameters were synthesized from bisphenol-A diglycidyl ether resin encapsulated within a self-assembled, polystyrene-montmorillonite hybrid nanocomposite (PCN) template and in situ cross-linked with polyamine curing agent. The size and wall thickness of the EPV vesicles were shown to be controlled by the epoxy resin concentration up to a critical epoxy concentration of 20 wt %, beyond which the wall thickness alone was found to be increasing. The EPVs dispersed in a polystyrene matrix at a loading of 2 wt % were found to reduce the dielectric constant of polystyrene from 3.1 to 2.0, and a linear decrease with decreasing wall thickness of the EPV, attributed to the increase in free volume involving the intrinsic porosity from the rigid epoxy vesicles and the composite, exhibited improved thermal stability also. The result suggests that vesicles produced by micromolding using self-assembled PCN can be utilized for the synthesis of polymer microcomposites having good interfacial bonding as well as low dielectric constant and good thermal stability for use in electronic packaging applications. PMID- 26140516 TI - Comparison of Atmospheric Pressure Ionization Gas Chromatography-Triple Quadrupole Mass Spectrometry to Traditional High-Resolution Mass Spectrometry for the Identification and Quantification of Halogenated Dioxins and Furans. AB - The goal of this study was to qualify gas chromatography coupled to atmospheric pressure ionization tandem mass spectrometry (APGC-MS/MS) as a reliable and valid technique for analysis of halogenated dioxins and furans that could be used in place of more traditional gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS) analysis. A direct comparison of the two instrumental techniques was performed. APGC-MS/MS system sensitivity was demonstrated to be on the single femtogram level. The APGC-MS/MS analysis also demonstrated method detection limits (MDLs) in both sediment and fish that were 2-18 times lower than those determined for the GC-HRMS. Inlet conditions were established to prevent issues with sample carry-over, due largely to the enhanced sensitivity of this technique. Additionally, this work utilized direct injection for sample introduction through the split/splittless inlet. Finally, quantification of both sediment and fish certified reference materials were directly compared between the APGC-MS/MS and GC-HRMS. The APGC-MS/MS performed similarly to, if not better than, the GC-HRMS instrument in the analysis of these samples. This data is intended to substantiate APGC-MS/MS as a comparable technique to GC-HRMS for the analysis of dioxins and furans. PMID- 26140518 TI - Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation. AB - BACKGROUND: For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others. OBJECTIVES: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT. DATA SOURCES: MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources. REVIEW METHODS: Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness. RESULTS: The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research. LIMITATIONS: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS: The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002461. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26140519 TI - Biomimetic mineralization of collagen fibrils induced by amine-terminated PAMAM dendrimers--PAMAM dendrimers for remineralization. AB - OBJECTIVE: Achieving biomimetic mineralization of collagen fibrils by mimicking the role of non-collagenous proteins (NCPs) with biomimetic analogs is of great interest in the fields of material science and stomatology. Amine-terminated PAMAM dendrimer (PAMAM-NH2), which possesses a highly ordered architecture and many calcium coordination sites, may be a desirable template for simulating NCPs to induce mineralization of collagen fibrils. In this study, we focused on the ability of PAMAM-NH2 to mineralize collagen fibrils. DESIGN: Type-I collagen fibrils were reconstituted over 400-mesh formvar-and-carbon-coated gold grids and treated with a third-generation PAMAM-NH2 (G3-PAMAM-NH2) solution. The treated collagen fibrils were immersed in artificial saliva for different lengths of time. The morphologies of the mineralized reconstituted type-I collagen fibrils were characterized by transmission electron microscopy. RESULTS: No obvious mineralized collagen fibrils were detected in the control group. On the contrary, collagen fibrils were heavily mineralized in the experimental group. Most importantly, intrafibrillar mineralization was achieved within the reconstituted type-I collagen fibrils. CONCLUSIONS: In this study, we successfully induced biomimetic mineralization within type-I collagen fibrils using G3-PAMAM-NH2. This strategy may serve as a potential therapeutic technique for restoring completely demineralized collagenous mineralized tissues. PMID- 26140517 TI - Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation. AB - SIGNIFICANCE: Nitric oxide (NO) is a critical signaling molecule marked by complex chemistry and varied biological responses depending on the context of the redox environment. In the setting of inflammation, NO can not only contribute to tissue injury and be causative of oxidative damage but can also signal as an adaptive molecule to limit inflammatory signaling in multiple cell types and tissues. RECENT ADVANCES: An advance in our understanding of NO biology was the recognition of the nitrate-nitrite-NO axis, whereby nitrate (predominantly from dietary sources) could be converted to nitrite and nitrite could be reduced to NO. CRITICAL ISSUES: Intriguingly, the recognition of multiple enzymes that serve as nitrite reductases in the setting of hypoxia or ischemia established the concept of nitrite as a circulating endocrine reservoir of NO, with the selective release of NO at sites that were primed for this reaction. This review highlights the anti-inflammatory roles of nitrite in numerous clinical conditions, including ischemia/reperfusion, transplant, cardiac arrest, and vascular injury, and in gastrointestinal inflammation. FUTURE DIRECTIONS: These preclinical and clinical investigations set up further clinical trials and studies that elucidate the endogenous role this pathway plays in protection against inflammatory signaling. PMID- 26140520 TI - Anti-Inflammatory Effects of Capsaicin and Piperine on Helicobacter pylori Induced Chronic Gastritis in Mongolian Gerbils. AB - BACKGROUND: Spices have been used for thousands of years, and recent studies suggest that certain spices confer beneficial effects on gastric disorders. The purpose of this study was to evaluate possible chemopreventive effects of spice derived compounds on Helicobacter pylori (H. pylori)-induced gastritis. METHODS: We examined the inhibitory effects of curcumin, capsaicin, and piperine on H. pylori in vitro by determining the colony-forming units and real-time RT-PCR in H. pylori stimulated AGS gastric cancer cells. For in vivo analysis, 6-week-old SPF male Mongolian gerbils were infected with H. pylori, fed diets containing 5000 ppm curcumin, 100 ppm capsaicin, or 100 ppm piperine, and sacrificed after 13 weeks. RESULTS: All three compounds inhibited in vitro proliferation of H. pylori, with curcumin being the most effective. Infiltration of neutrophils and mononuclear cells was suppressed by piperine both in the antrum and corpus of H. pylori-infected gerbils. Capsaicin also decreased neutrophils in the antrum and corpus and mononuclear cell infiltration and heterotopic proliferative glands in the corpus. mRNA expression of Tnf-alpha and formation of phospho-IkappaB-alpha in the antrum were reduced by both capsaicin and piperine. In addition, piperine suppressed expression of Il-1beta, Ifn-gamma, Il-6, and iNos, while H. pylori UreA and other virulence factors were not significantly attenuated by any compounds. CONCLUSION: These results suggest that capsaicin and piperine have anti-inflammatory effects on H. pylori-induced gastritis in gerbils independent of direct antibacterial effects and may thus have potential for use in the chemoprevention of H. pylori-associated gastric carcinogenesis. PMID- 26140521 TI - Driving Errors in Persons with Dementia. AB - OBJECTIVES: To differentiate driving errors in persons with dementia who fail a performance- based road test from errors in persons who pass. DESIGN: Cross sectional. SETTING: Community. PARTICIPANTS: Active drivers diagnosed with dementia (n = 60) and older adult controls (n = 32). MEASUREMENT: All participants completed a standardized clinical and on-road driving assessment. The outcome variable was the number and types of driving errors according to the Record of Driving Errors (RODE), a standardized tool to record driving errors. RESULTS: Sixty-two percent (n = 37) of individuals with dementia and 3% (n = 1) of controls failed the road test. Based on the RODE, individuals with dementia made twice as many driving errors as healthy controls. Within the dementia sample, individuals who failed the road test had more difficulties driving straight and making left and right turns than during lane changes. Dangerous actions occurred most often while driving straight and making left turns. Specific driving behaviors associated with road test failure in the sample with dementia included difficulties in lane positioning and usage, stopping the vehicle appropriately, attention, decision-making, and following rules of the road. Informants of participants with dementia who failed the road test reported more impairment with cognitive functioning on the Assessing Dementia 8 Screening Interview (AD8). CONCLUSION: This report highlights the driving errors most common in people with dementia who fail a road test. The finding that most of the dangerous actions in the sample with dementia occurred while driving straight condition is novel. Driving on straight roads has not been considered a condition of "high challenge" in prior driving studies in individuals with dementia. This finding has potential implications for future interventions related to vehicle instrumentation and driving recommendations for people with dementia. PMID- 26140522 TI - Tobacco, Nicotine, and Headache. AB - BACKGROUND: Migraineurs variably attribute the cause of their headache to tobacco exposure, whereas tobacco is often stated to cause headache-related disability worldwide. Given tobacco's physiological and emotional addictiveness and migraine's substantial economic impact, improved functionality can be difficult for those with migraine exposed to tobacco products. Environmental tobacco exposure in indoor spaces and workplaces is associated with exacerbation of headache. Avoidance of headache triggers is included in most comprehensive migraine treatment programs, yet tobacco awareness, avoidance, or coping is rarely emphasized as part of that regimen. OBJECTIVE: The aims of this study were to examine the various types of tobacco products to which headache sufferers are exposed and the known basic mechanisms by which tobacco (nicotine) exposure promotes headache pain, and to review the extensive literature on tobacco related to headache with a detailed descriptive narrative providing the basis for conclusions regarding association of noncluster headache-related tobacco exposure. Tobacco-related recommendations are offered. METHODS: MEDLINE, EMBASE, and Google Scholar databases were searched without yearly restriction through the date of submission (May 2015), using the MeSH terms "tobacco," "tobacco products," "smoking," "tobacco use," "headache," and "headache disorders." The selection of articles was not limited to English studies or to humans. Articles were excluded when "headache" and "tobacco" were not both mentioned with data provided. Case series were included. Bibliographies of all articles were screened for additional relevant articles. RESULTS: Although migraineurs worldwide report tobacco smoke among triggers, it is rarely among the highest in frequency, and biases abound with predominantly noncontrolled retrospective data. Prospective population-based diary data are extremely limited, and no controlled trials exist to confirm a cause and effect for headache of any type. Although some studies are nonsupportive and even conflicting, headache, pain, and tobacco exposure currently remain associated. CONCLUSION: Conflicting data support the validity of patient-reported environmental tobacco exposure as a headache trigger. Prospective controlled studies are needed, but unlikely to be performed, to determine the extent that tobacco influences the headache process, in addition to other under-recognized factors. Meanwhile, because of numerous other negative health effects, decreased tobacco exposure should be recommended to headache patients of all ages in hopes of decreasing disability and improving functionality. PMID- 26140523 TI - Bilateral subretinal abscesses: the first case of disseminated Nocardia beijingensis in Australia. PMID- 26140524 TI - Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel. AB - OBJECTIVE: Perampanel, a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl 4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, is indicated for adjunctive treatment of partial seizures in patients >=12 years based on three phase III clinical studies. The perampanel U.S. Prescribing Information includes a boxed warning for serious psychiatric and behavioral adverse reactions. To provide context for this warning, detail on psychiatric and behavioral safety data from perampanel clinical studies is presented. METHODS: An analysis of pooled safety data from three phase III studies in patients with partial seizures is presented. Data from phase I and phase II studies in patients with and without epilepsy were also analyzed. Psychiatric and behavioral treatment-emergent adverse events (TEAEs) were evaluated according to Medical Dictionary for Regulatory Activities (MedDRA) terms, using "narrow" and "narrow-and-broad" standardized MedDRA queries (SMQs) for TEAEs suggestive of hostility/aggression. RESULTS: From the three phase III partial-seizure studies, the overall rate of psychiatric TEAEs was higher in the 8 mg (17.2%) and 12 mg (22.4%) perampanel groups versus placebo (12.4%). In the "narrow" SMQ, hostility/aggression TEAEs were observed in 2.8% for 8 mg and 6.3% for 12 mg perampanel groups, versus 0.7% of placebo patients. "Narrow-and-broad" SMQs for hostility/aggression TEAE rates were 12.3% for 8 mg and 20.4% for 12 mg perampanel groups, versus 5.7% for placebo; rates for events resulting in discontinuation were perampanel = 1.6% versus placebo = 0.7%. For events reported as serious AEs (SAEs), rates were perampanel = 0.7% versus placebo = 0.2%. In nonepilepsy patients, psychiatric TEAEs were similar between patients receiving perampanel and placebo. In phase I subjects/volunteers, all psychiatric TEAEs were mild or moderate. These analyses suggest that psychiatric adverse effects are associated with use of perampanel. SIGNIFICANCE: Patients and caregivers should be counseled regarding the potential risk of psychiatric and behavioral events with perampanel in patients with partial seizures; patients should be monitored for these events during treatment, especially during titration and at higher doses. PMID- 26140525 TI - Synergistic effect of targeting the epidermal growth factor receptor and hyaluronan synthesis in oesophageal squamous cell carcinoma cells. AB - BACKGROUND AND PURPOSE: Worldwide, oesophageal cancer is the eighth most common cancer and has a very poor survival rate. In order to identify new tolerable treatment options for oesophageal squamous cell carcinoma (ESCC), erlotinib was tested with moderate efficacy in phase I and II studies. As 4-methylumbelliferone (4-MU), an hyaluronan (HA) synthesis inhibitor showed anti-cancer effects in vitro, and in ESCC xenograft tumours, we investigated whether the anti-cancer effects of erlotinib could be augmented by combining it with 4-MU. EXPERIMENTAL APPROACH: ESCC cell lines were treated with erlotinib or gefitinib (1 MUmol.L-1 ) and 4-MU (300 MUmol.L-1 ), and the cell count, cell cycle progression and migration were determined as compared to the single agents and the solvent control. KEY RESULTS: The combination of erlotinib and 4-MU synergistically inhibited the proliferation of ESCC cell lines. Furthermore, the migration speed of ESCC cell line KYSE-410 in gap closure assays was significantly reduced by the combination of erlotinib and 4-MU. Decreased ERK phosphorylation could explain the anti-proliferative and anti-migratory effects in the combined treatment group. Finally, the combination was additionally able to decrease the growth of multicellular tumour spheroids, a three-dimensional cell culture model that was associated with sustained inhibition of ERK1/2 phosphorylation. CONCLUSIONS AND IMPLICATIONS: The combination of 4-MU and erlotinib showed promising anti-cancer efficacies in the ESCC cell lines. PMID- 26140526 TI - Elevated Serum Level of Interleukin 17 in a Population With Prehypertension. AB - Cytokines play an important role in the pathogenesis of hypertension. The authors hypothesized that interleukin 17 (IL-17) might contribute to the prehypertensive state. This study evaluated the relationship between serum levels of IL-17 and prehypertension. A total of 394 participants were enrolled, after excluding for hypertension or treated hypertension, and divided into two groups (optimal blood pressure [BP] and prehypertension) based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification of BP. Optimal BP was defined as systolic BP <120 mm Hg and diastolic BP <80 mm Hg. Prehypertension was defined as systolic BP of 120 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg. IL-17A levels were determined by enzyme-linked immunosorbent assay. The mean serum IL-17 concentration in the prehypertension group was significantly higher than in the optimal BP group. The cohort was divided into quartiles Q1 (<=3.5 ng/L), Q2 (3.60 to 6.10 ng/L), Q3 (6.20 to 10.00 ng/L), and Q4 (>=10.10 ng/L) based on IL-17 levels. The Q2 to Q4 groups had increasing odds ratios for having prehypertension compared with the Q1 group. Elevated serum IL-17 was accompanied by a rise in systolic BP. Thus, increased serum IL-17 levels are associated with prehypertension. PMID- 26140527 TI - Ibopamine challenge testing differentiates glaucoma suspect, stable glaucoma and progressive glaucoma cases. AB - BACKGROUND: An ibopamine challenge is a novel technique for assessing glaucoma using ibopamine, a topical drug which temporarily increases aqueous production. We aimed to determine whether change in intraocular pressure (IOP) and/or optic cup volume (OCV) during the test differentiated between glaucoma patients at different stages of disease; namely, glaucoma suspects (GS), glaucoma patients who are stable (SG) and glaucoma patients who have demonstrated rapid progression (PG). DESIGN: Non-randomized clinical trial evaluating a diagnostic test. PARTICIPANTS: Sixty-one patients were recruited through glaucoma clinics at the Flinders Medical Centre (24 GS, 24 SG and 13 PG). METHODS: Patients underwent IOP measurement and OCV assessment using optical coherence tomography. Two drops of ibopamine 2% solution were instilled into the study eye of each patient. After 45 min, IOP and OCV were reassessed. Changes from baseline were compared between groups. MAIN OUTCOME MEASURE: Change in IOP and OCV after ibopamine challenge. RESULTS: Following the ibopamine challenge, IOP increased by 1.8 mmHg for GS patients, 4.5 mmHg for SG patients (P = 0.003) and 8.1 mmHg for PG patients (P < 0.0001). OCV increased by 0.2% for GS patients, 0.6% for SG patients and 5.5% for PG patients. This was not significantly different between GS patients and SG patients; however, it was significantly different between GS patients and PG patients (P < 0.0001), and between SG and PG patients (P = 0.001). CONCLUSION: GS patients may be differentiated from those with SG or PG by their IOP response, and SG may be differentiated from PG patients by their change in OCV following an ibopamine challenge. PMID- 26140528 TI - Does altering the occlusal vertical dimension produce temporomandibular disorders? A literature review. AB - The purpose of this review was to present a comprehensive review of the scientific evidence available in the literature regarding the effect of altering the occlusal vertical dimens-ion (OVD) on producing temporomandibular disorders. The authors conducted a PubMed search with the following search terms 'temporoman dibular disorders', 'occlusal vertical dimension', 'stomatognatic system', 'masticatory muscles' and 'skeletal muscle'. Bibliographies of all retrieved articles were consulted for additional publications. Hand-searched publications from 1938 were included. The literature review revealed a lack of well-designed studies. Traditional beliefs have been based on case reports and anecdotal opinions rather than on well-controlled clinical trials. The available evidence is weak and seems to indicate that the stomatognathic system has the ability to adapt rapidly to moderate changes in occlusal vertical dimension (OVD). Nevertheless, it should be taken into consideration that in some patients mild transient symptoms may occur, but they are most often self-limiting and without major consequence. In conclusion, there is no indication that permanent alteration in the OVD will produce long-lasting TMD symptoms. However, additional studies are needed. PMID- 26140529 TI - Ecophysiology of an uncultivated lineage of Aigarchaeota from an oxic, hot spring filamentous 'streamer' community. AB - The candidate archaeal phylum 'Aigarchaeota' contains microorganisms from terrestrial and subsurface geothermal ecosystems. The phylogeny and metabolic potential of Aigarchaeota has been deduced from several recent single-cell amplified genomes; however, a detailed description of their metabolic potential and in situ transcriptional activity is absent. Here, we report a comprehensive metatranscriptome-based reconstruction of the in situ metabolism of Aigarchaeota in an oxic, hot spring filamentous 'streamer' community. Fluorescence in situ hybridization showed that these newly discovered Aigarchaeota are filamentous, which is consistent with the presence and transcription of an actin-encoding gene. Aigarchaeota filaments are intricately associated with other community members, which include both bacteria (for example, filamentous Thermocrinis spp.) and archaea. Metabolic reconstruction of genomic and metatranscriptomic data suggests that this aigarchaeon is an aerobic, chemoorganoheterotroph with autotrophic potential. A heme copper oxidase complex was identified in the environmental genome assembly and highly transcribed in situ. Potential electron donors include acetate, fatty acids, amino acids, sugars and aromatic compounds, which may originate from extracellular polymeric substances produced by other microorganisms shown to exist in close proximity and/or autochthonous dissolved organic carbon (OC). Transcripts related to genes specific to each of these potential electron donors were identified, indicating that this aigarchaeon likely utilizes several OC substrates. Characterized members of this lineage cannot synthesize heme, and other cofactors and vitamins de novo, which suggests auxotrophy. We propose the name Candidatus 'Calditenuis aerorheumensis' for this aigarchaeon, which describes its filamentous morphology and its primary electron acceptor, oxygen. PMID- 26140530 TI - Metagenomic study of red biofilms from Diamante Lake reveals ancient arsenic bioenergetics in haloarchaea. AB - Arsenic metabolism is proposed to be an ancient mechanism in microbial life. Different bacteria and archaea use detoxification processes to grow under high arsenic concentration. Some of them are also able to use arsenic as a bioenergetic substrate in either anaerobic arsenate respiration or chemolithotrophic growth on arsenite. However, among the archaea, bioenergetic arsenic metabolism has only been found in the Crenarchaeota phylum. Here we report the discovery of haloarchaea (Euryarchaeota phylum) biofilms forming under the extreme environmental conditions such as high salinity, pH and arsenic concentration at 4589 m above sea level inside a volcano crater in Diamante Lake, Argentina. Metagenomic analyses revealed a surprisingly high abundance of genes used for arsenite oxidation (aioBA) and respiratory arsenate reduction (arrCBA) suggesting that these haloarchaea use arsenic compounds as bioenergetics substrates. We showed that several haloarchaea species, not only from this study, have all genes required for these bioenergetic processes. The phylogenetic analysis of aioA showed that haloarchaea sequences cluster in a novel and monophyletic group, suggesting that the origin of arsenic metabolism in haloarchaea is ancient. Our results also suggest that arsenite chemolithotrophy likely emerged within the archaeal lineage. Our results give a broad new perspective on the haloarchaea metabolism and shed light on the evolutionary history of arsenic bioenergetics. PMID- 26140531 TI - Density-dependent adaptive resistance allows swimming bacteria to colonize an antibiotic gradient. AB - During antibiotic treatment, antibiotic concentration gradients develop. Little is know regarding the effects of antibiotic gradients on populations of nonresistant bacteria. Using a microfluidic device, we show that high-density motile Escherichia coli populations composed of nonresistant bacteria can, unexpectedly, colonize environments where a lethal concentration of the antibiotic kanamycin is present. Colonizing bacteria establish an adaptively resistant population, which remains viable for over 24 h while exposed to the antibiotic. Quantitative analysis of multiple colonization events shows that collectively swimming bacteria need to exceed a critical population density in order to successfully colonize the antibiotic landscape. After colonization, bacteria are not dormant but show both growth and swimming motility under antibiotic stress. Our results highlight the importance of motility and population density in facilitating adaptive resistance, and indicate that adaptive resistance may be a first step to the emergence of genetically encoded resistance in landscapes of antibiotic gradients. PMID- 26140532 TI - Functional environmental proteomics: elucidating the role of a c-type cytochrome abundant during uranium bioremediation. AB - Studies with pure cultures of dissimilatory metal-reducing microorganisms have demonstrated that outer-surface c-type cytochromes are important electron transfer agents for the reduction of metals, but previous environmental proteomic studies have typically not recovered cytochrome sequences from subsurface environments in which metal reduction is important. Gel-separation, heme-staining and mass spectrometry of proteins in groundwater from in situ uranium bioremediation experiments identified a putative c-type cytochrome, designated Geobacter subsurface c-type cytochrome A (GscA), encoded within the genome of strain M18, a Geobacter isolate previously recovered from the site. Homologs of GscA were identified in the genomes of other Geobacter isolates in the phylogenetic cluster known as subsurface clade 1, which predominates in a diversity of Fe(III)-reducing subsurface environments. Most of the gscA sequences recovered from groundwater genomic DNA clustered in a tight phylogenetic group closely related to strain M18. GscA was most abundant in groundwater samples in which Geobacter sp. predominated. Expression of gscA in a strain of Geobacter sulfurreducens that lacked the gene for the c-type cytochrome OmcS, thought to facilitate electron transfer from conductive pili to Fe(III) oxide, restored the capacity for Fe(III) oxide reduction. Atomic force microscopy provided evidence that GscA was associated with the pili. These results demonstrate that a c-type cytochrome with an apparent function similar to that of OmcS is abundant when Geobacter sp. are abundant in the subsurface, providing insight into the mechanisms for the growth of subsurface Geobacter sp. on Fe(III) oxide and suggesting an approach for functional analysis of other Geobacter proteins found in the subsurface. PMID- 26140533 TI - Phylogenetic congruence and ecological coherence in terrestrial Thaumarchaeota. AB - Thaumarchaeota form a ubiquitously distributed archaeal phylum, comprising both the ammonia-oxidising archaea (AOA) and other archaeal groups in which ammonia oxidation has not been demonstrated (including Group 1.1c and Group 1.3). The ecology of AOA in terrestrial environments has been extensively studied using either a functional gene, encoding ammonia monooxygenase subunit A (amoA) or 16S ribosomal RNA (rRNA) genes, which show phylogenetic coherence with respect to soil pH. To test phylogenetic congruence between these two markers and to determine ecological coherence in all Thaumarchaeota, we performed high throughput sequencing of 16S rRNA and amoA genes in 46 UK soils presenting 29 available contextual soil characteristics. Adaptation to pH and organic matter content reflected strong ecological coherence at various levels of taxonomic resolution for Thaumarchaeota (AOA and non-AOA), whereas nitrogen, total mineralisable nitrogen and zinc concentration were also important factors associated with AOA thaumarchaeotal community distribution. Other significant associations with environmental factors were also detected for amoA and 16S rRNA genes, reflecting different diversity characteristics between these two markers. Nonetheless, there was significant statistical congruence between the markers at fine phylogenetic resolution, supporting the hypothesis of low horizontal gene transfer between Thaumarchaeota. Group 1.1c Thaumarchaeota were also widely distributed, with two clusters predominating, particularly in environments with higher moisture content and organic matter, whereas a similar ecological pattern was observed for Group 1.3 Thaumarchaeota. The ecological and phylogenetic congruence identified is fundamental to understand better the life strategies, evolutionary history and ecosystem function of the Thaumarchaeota. PMID- 26140534 TI - A novel insulinotropic mechanism of whole grain-derived gamma-oryzanol via the suppression of local dopamine D2 receptor signalling in mouse islet. AB - BACKGROUND AND PURPOSE: gamma-Oryzanol, derived from unrefined rice, attenuated the preference for dietary fat in mice, by decreasing hypothalamic endoplasmic reticulum stress. However, no peripheral mechanisms, whereby gamma-oryzanol could ameliorate glucose dyshomeostasis were explored. Dopamine D2 receptor signalling locally attenuates insulin secretion in pancreatic islets, presumably via decreased levels of intracellular cAMP. We therefore hypothesized that gamma oryzanol would improve high-fat diet (HFD)-induced dysfunction of islets through the suppression of local D2 receptor signalling. EXPERIMENTAL APPROACH: Glucose metabolism and regulation of molecules involved in D2 receptor signalling in pancreatic islets were investigated in male C57BL/6J mice, fed HFD and treated with gamma-oryzanol . In isolated murine islets and the beta cell line, MIN6 , the effects of gamma-oryzanol on glucose-stimulated insulin secretion (GSIS) was analysed using siRNA for D2 receptors and a variety of compounds which alter D2 receptor signalling. KEY RESULTS: In islets, gamma-oryzanol enhanced GSIS via the activation of the cAMP/PKA pathway. Expression of molecules involved in D2 receptor signalling was increased in islets from HFD-fed mice, which were reciprocally decreased by gamma-oryzanol. Experiments with siRNA for D2 receptors and D2 receptor ligands in vitro suggest that gamma-oryzanol suppressed D2 receptor signalling and augmented GSIS. CONCLUSIONS AND IMPLICATIONS: gamma Oryzanol exhibited unique anti-diabetic properties. The unexpected effects of gamma-oryzanol on D2 receptor signalling in islets may provide a novel; natural food-based, approach to anti-diabetic therapy. PMID- 26140535 TI - Effectiveness of a combined (4% chlorhexidine digluconate shampoo and solution) protocol in MRS and non-MRS canine superficial pyoderma: a randomized, blinded, antibiotic-controlled study. AB - BACKGROUND: There is a lack of studies comparing topical antiseptics to systemic antibiotics in the treatment of canine superficial pyoderma. HYPOTHESIS/OBJECTIVES: To compare the efficacy of topical chlorhexidine with systemic amoxicillin-clavulanic acid for the treatment of canine superficial pyoderma. ANIMALS: A randomized controlled trial was conducted in dogs with superficial pyoderma. Group T (n = 31) was treated topically with 4% chlorhexidine digluconate shampoo (twice weekly) and solution (once daily) for 4 weeks. Group S (n = 20) was treated orally with amoxicillin-clavulanic acid (25 mg/kg) twice daily for 4 weeks. METHODS: Bacterial culture and susceptibility testing were performed on clinical specimens collected before treatment. Severity of lesions and number of intracellular bacteria were evaluated using four-point scales to calculate a total pyoderma score for each dog. Pruritus was assessed by owners using a visual analog scale (range 0-10). Scores were analysed for statistical differences between groups T and S. RESULTS: Staphylococcus pseudintermedius was isolated from 48 dogs, including eight meticillin-resistant strains (MRSP). Although the number of dogs was small, no significant differences in pyoderma and pruritus scores were observed between groups throughout the study except for day 1, when group S had a significantly higher total score than group T (P = 0.03). Treatment with chlorhexidine products resulted in resolution of clinical signs in all dogs including those infected with MRSP. CONCLUSION AND CLINICAL IMPORTANCE: Topical therapy with chlorhexidine digluconate products may be as effective as systemic therapy with amoxicillin-clavulanic acid. This finding supports the current recommendations to use topical antiseptics alone for the management of superficial pyoderma. PMID- 26140536 TI - A new method to validate thoracic CT-CT deformable image registration using auto segmented 3D anatomical landmarks. AB - BACKGROUND: Deformable image registrations are prone to errors in aligning reliable anatomically features. Consequently, identification of registration inaccuracies is important. Particularly thoracic three-dimensional (3D) computed tomography (CT)-CT image registration is challenging due to lack of contrast in lung tissue. This study aims for validation of thoracic CT-CT image registration using auto-segmented anatomically landmarks. MATERIAL AND METHODS: Five lymphoma patients were CT scanned three times within a period of 18 months, with the initial CT defined as the reference scan. For each patient the two successive CT scans were registered to the reference CT using three different image registration algorithms (Demons, B-spline and Affine). The image registrations were evaluated using auto-segmented anatomical landmarks (bronchial branch points) and Dice Similarity Coefficients (DSC). Deviation of corresponding bronchial landmarks were used to quantify inaccuracies in respect of both misalignment and geometric location within lungs. RESULTS: The median bronchial branch point deviations were 1.6, 1.1 and 4.2 (mm) for the three tested algorithms (Demons, B-spline and Affine). The maximum deviations (> 15 mm) were found within both Demons and B-spline image registrations. In the upper part of the lungs the median deviation of 1.7 (mm) was significantly different (p < 0.02) relative to the median deviations of 2.0 (mm), found in the middle and lower parts of the lungs. The DSC revealed similar registration discrepancies among the three tested algorithms, with DSC values of 0.96, 0.97 and 0.91, for respectively Demons, B-spline and the Affine algorithms. CONCLUSION: Bronchial branch points were found useful to validate thoracic CT-CT image registration. Bronchial branch points identified local registration errors > 15 mm in both Demons and B-spline deformable algorithms. PMID- 26140538 TI - The colour of a football outfit affects visibility and team success. AB - We investigated the impact of the colour of football outfits on localising football players and on the results of football matches. Two studies were conducted: an experimental study examining the effects of outfit colour on the assessment of the positions of computer-animated football players in a video set up (study 1) and a retrospective study on professional football clubs' performances dependent on their outfit colours (study 2). The studies were conducted with 18 human volunteers aged 15-18 years (study 1) and league results from 10 professional European football teams over 17 years (1995-2013) (study 2). We analysed the number of correct assessments of the positions of virtual football players with different outfit colours (study 1) and analysed the relationship between match results and outfits' colours (study 2). Study 1 showed that the position of players wearing white outfits was better assessed in 5.2% of the trials compared to players wearing green outfits (P = 0.007). Study 2 showed that Manchester City conceded less goals against in away games in highly visible kits (r = 0.62; P = 0.024), while Newcastle United conceded less goals and won more points while playing in kits associated with low visibility (r = 0.63; P = 0.007; r = 0.50; P = 0.040, respectively). We conclude that the colour of football outfits affects evaluations of football players' positions on the field, with white tricots resulting in the best location assessment. The outfit colour may indirectly influence football match results, warranting more attention to the home and away shirts by team managers and football scientists. PMID- 26140537 TI - Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease. AB - Interleukin-8 (IL-8) is a neutrophil chemokine that is encoded on the CXCL8 gene. Normally CXCL8 expression is repressed due to histone deacetylation, octamer-1 binding to the promoter and the inhibitory effect of nuclear factor-kappaB repressing factor (NRF). However, in response to a suitable stimulus, the human CXCL8 gene undergoes transcription due to its inducible promoter that is regulated by the transcription factors nuclear factor-kappaB (NF-kappaB), activating protein (AP-1), CAAT/enhancer-binding protein beta (C/EBPbeta, also known as NF-IL-6), C/EBP homologous protein (CHOP) and cAMP response element binding protein (CREB). CXCL8 mRNA is then stabilised by the activity of p38 mitogen-activated protein kinase (p38 MAPK). Cystic fibrosis (CF) lung disease is characterised by a neutrophil-dominated airway inflammatory response. A major factor contributing to the large number of neutrophils is the higher than normal levels of IL-8 that are present within the CF lung. Infection and inflammation, together with intrinsic alterations in CF airway cells are responsible for the abnormally high intrapulmonary levels of IL-8. Strategies to inhibit aberrantly high CXCL8 expression hold therapeutic potential for CF lung disease. PMID- 26140539 TI - Effects of Fuzhuan Brick-Tea Water Extract on Mice Infected with E. coli O157:H7. AB - Fuzhuan brick-tea extract (FBTE) affects the physiology of mice infected with Escherichia coli O157:H7. For 10 consecutive days, 0.05, 0.5, and 1.0 g/mL FBTE was administered intragastrically to three groups of infected Kunming mice, and changes in immunological function, hematology, and histopathology were examined. The results revealed upregulation of platelets, total protein, and albumin along with downregulation of serum triglycerides, aspartate aminotransferase, creatinine, and urea nitrogen in FBTE-treated mice. Histological sections of stomach, kidney, duodenum, ileum, and colon suggested that infected mucous membranes could be rehabilitated by low- and high-dose FBTE and that inflammation was alleviated. Similarly, increased thymic function in mice treated with middle- and high-dose FBTE led to elevated serum hemolysin antibody titer and increased CD4+ and CD8+ T cells, as indicated by CD4+ and CD8+ expression on intestinal mucosa. Monocyte and macrophage function was improved by three FBTE dosages tested. Colonic microbiota analysis by denaturing gradient gel electrophoresis (DGGE) revealed characteristic bands in infected mice treated with middle- and high-dose FBTE and increased species diversity in Lactobacillus, Bacteroides, and Clostridium cluster IV. These results suggest that FBTE may protect kidney and liver of mice infected with E. coli O157:H7, improve immune function, and regulate the colonic microbiota. PMID- 26140540 TI - Dietary Fiber Intake is Associated with Increased Colonic Mucosal GPR43+ Polymorphonuclear Infiltration in Active Crohn's Disease. AB - G protein-coupled receptor 43/free fatty acid receptor 2 (GPR43/FFAR2) is essential for polymorphonuclear (PMN) recruitment. We investigated the expression of GPR43/FFAR2 in the colon from Crohn's disease patients and whether dietary fiber in enteral nutrition increases GPR43+ polymorphonuclear infiltration in mucosa. Segments of ascending colon and white blood cells from peripheral blood were obtained from 46 Crohn's disease patients and 10 colon cancer patients. The Crohn's disease patients were grouped by the activity of disease (active or remission) and enteral nutrition with or without dietary fiber. Histological feature, expression and location of GPR43/FFAR2 and level of tumor necrosis factor-alpha (TNF-alpha), interleukine-6 (IL-6) and myeloperoxidase were assessed. The results of hematoxylin-eosin and immunohistochemistry staining revealed that the infiltration of immune cells, including GPR43+ PMN, was more severe in active Crohn's disease patients who consumed normal food or enteral nutrition with dietary fiber than in remission patients and colon cancer patients. This finding was supported by the results of GPR43 and myeloperoxidase expression. Active Crohn's disease (CD) patients who consumed enteral nutrition without dietary fiber exhibited severe immune cell infiltration similar to the other active CD patients, but GPR43+ PMNs were rarely observed. The level of TNF alpha mRNA in active Crohn's disease patients was higher than those of the other patients. In conclusion, the use of dietary fiber in enteral nutrition by active Crohn's disease patients might increase GPR43+ PMNs infiltration in colon mucosa. This effect was not observed in Crohn's disease patients in remission. PMID- 26140542 TI - Blood flow occlusion pressure at rest and immediately after a bout of low load exercise. AB - The purpose of this study was to determine whether arm circumference is predictive of arterial occlusion in the standing position and to determine the change in pressure before and immediately after exercise. Thirty-one participants had their arm circumference, blood pressure and standing arterial occlusion determined before exercise. Participants then completed elbow flexions at 40% of resting arterial occlusion at 30% of their one repetition maximum (1RM). The goal repetitions for the exercise included one set of 30 repetitions followed by 3 sets of 15, with 30s rest between sets. Immediately following the last set, postexercise arterial occlusion was determined. Two different models of hierarchical linear regression were used to determine the greatest predictor of standing arterial occlusion. Our final model explained 69% of the variance in arterial occlusion with arm circumference (beta = 0.639, part = 0.568) explaining more than brachial systolic blood pressure (beta = 0.312, part = 0.277). Standing arterial occlusion increased from pre- [138 (15) mmHg] to post- [169 (20) mmHg] exercise (P<0.001). In conclusion, the cardiovascular response to blood flow restriction (BFR) in the upper arm following 4 sets of elbow flexion exercise decreases the relative arterial occlusion pressure. In addition, we confirm previous data that circumference explains the most unique variance in arterial occlusion pressure in the upper body. These findings are important as they provide additional insight into making the pressure more uniform between participants throughout exercise. PMID- 26140541 TI - Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults. AB - Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 +/- 3.3 year (mean +/- standard deviation (SD)); body mass index (BMI) 24.1 +/- 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) increased in all three groups, without an increase in circulating TNF-alpha. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed. PMID- 26140543 TI - Insulin resistance parameters in users of the injectable contraceptive depot medroxyprogesterone acetate during one year of use. AB - OBJECTIVES: The aim of the study was to assess insulin resistance parameters using successive homeostasis model assessment (HOMA) and clinical evaluations in healthy new users of depot medroxyprogesterone acetate (DMPA). METHODS: A prospective 12-month study was carried out to compare 31 DMPA users with 25 copper intrauterine device (Cu-IUD; TCu380A) users, matched for age (+/- 1 year) and body mass index (BMI; +/- 1 kg/m(2)). Participants met the following criteria: age 18 to 40 years, BMI < 30 kg/m(2), fasting glucose < 5.5 mmol/l, 2-h glucose after a 75 g oral glucose load < 140 mg/dl. BMI, waist circumference, fasting glucose, fasting insulin and HOMA of insulin resistance (HOMA-IR) were evaluated at baseline and after 6 and 12 months of contraceptive use. Insulin resistance was defined as a HOMA-IR value > 2.7. RESULTS: The DMPA group showed significant increases in BMI, waist circumference, fasting insulin and HOMA-IR throughout the observation period in relation to baseline. Significant increases in BMI and waist circumference were observed in the DMPA group at 12 months compared with the Cu-IUD group. Five DMPA users had abnormal HOMA-IR values, three of whom had gained > 5 kg in weight at 12 months. CONCLUSIONS: HOMA-IR represents a useful tool to indicate changes in carbohydrate metabolism in non obese DMPA users, especially when accompanied by measurement of clinical parameters such as BMI and waist circumference. PMID- 26140544 TI - Scillapersicene: a new homoisoflavonoid with cytotoxic activity from the bulbs of Scilla persica HAUSSKN. AB - The phytochemical investigation of Scilla persica HAUSSKN bulbs led to the isolation of a novel homoisoflavonoid that named Scillapersicene (1) and identified as 3-(3',4'-dihydroxybenzylidene)-8-hydroxy-5,7-dimethoxychroman-4-one along with five known homoisoflavonoids 2-6, whose structures were elucidated using HRFAB-MS, 1D and 2D NMR spectroscopic data. The known compounds were identified as 3-(3',4'-dihydroxybenzyl)-5,8-dihydroxy-7-methoxychroman-4-one (2), 3,9-dihydro-autumnalin (3), autumnalin (4), 3-(3',4'-dihydroxybenzylidene)-5,8 dihydroxy-7-methoxychroman-4-one (5) and scillapersicone (6). All compounds obtained, expect 2 and 4, showed strong cytotoxic activity against AGS cell line. The toxicity on AGS cell line was measured by 1, 3, 5 and 6 with IC50 values of 8.4, 30.5, 10.7 and 24.2 MUM, respectively. In addition, the physico-chemical properties of these natural compounds were optimised using density functional method (B3LYP) with standard 6-311+G* basis set. These natural products have low energy gaps between the first ionisation potentials and highest occupied molecular orbital. In conclusion, the low-energy gap could cause reason for cytotoxic activity of homoisoflavonoids. PMID- 26140545 TI - Efficient one-pot synthesis of 5-perfluoroalkylpyrazoles by cyclization of hydrazone dianions. AB - A highly selective and efficient method for the synthesis of 5 trifluoromethylated and 5-perfluoroalkylated pyrazoles has been developed which relies on the cyclization of hydrazine dianions with ethyl perfluorocarboxylates. The pyrazoles prepared were evaluated as potential inhibitors of alkaline phosphatases, namely human tissue non-specific alkaline phosphatase (h-TNAP) and tissue specific intestinal alkaline phosphatase (IAP). Most pyrazole derivatives inhibited h-IAP more markedly than h-TNAP and had minor effects on nucleotide pyrophosphatase/phosphodiesterases. Therefore, the compounds appear as potential selective inhibitors of h-IAP. PMID- 26140546 TI - Prognostic significance of PD-1 expression on peripheral blood CD4+ T cells in patients with newly diagnosed chronic lymphocytic leukemia. AB - INTRODUCTION: Recent studies in a mouse model of chronic lymphocytic leukemia (CLL) demonstrated that inhibition of the programmed death receptor 1 (PD-1)-PD L1 axis resulted in correction of leukemia-induced CD8+ T cell-related immune dysfunction and protected mice against CLL development. However, it remains unclear whether CLL development and progression can be also associated with CD4+ T cells expressing PD-1. OBJECTIVES: We aimed to analyze whether a quantitative assessment of CD4+PD-1+ T cells performed at the time of diagnosis can have prognostic significance in patients with CLL. PATIENTS AND METHODS: We examined 56 patients with newly diagnosed CLL at different stages of the disease. The quantitative assessment of PD-1-expressing CD4+ T cells was performed in all patients, using multicolor flow cytometry. RESULTS: We demonstrated that CLL patients with an advanced (high and intermediate risk) stage had a significantly higher number of CD4+PD-1+ T cells compared with subjects with low-grade disease. Importantly, we showed that the number of PD-1-expressing CD4+ T cells in the peripheral blood of patients referred for immediate treatment due to the advanced stage of the disease was significantly higher compared with subjects on watchful waiting. Finally, we found that treatment-naive patients with higher numbers of CD4+PD-1+ T cells at baseline showed a significantly shortened time to the first treatment compared with patients with a low number of CD4+PD-1+ T cells. CONCLUSIONS: Our study showed that the quantative assessment of CD4+PD-1+ T cells in peripheral blood using flow cytometry can facilitate prognostication of patients with newly diagnosed CLL. PMID- 26140547 TI - Enhanced fluorescence detection of miRNA-16 on a photonic crystal. AB - We report a novel sensing method for fluorescence-labelled microRNAs (miRNAs) spotted on an all-dielectric photonic structure. Such a photonic structure provides an enhanced excitation and a directional beaming of the emitted fluorescence, resulting in a significant improvement of the overall signal collected. As a result, the Limit of Detection (LoD) is demonstrated to decrease by a factor of about 50. A compact read-out system allows a wide-field imaging based detection, with little or no optical alignment issues, which makes this approach particularly interesting for further development for example in microarray-type bioassays. PMID- 26140548 TI - Recent advances in the use of vibrational chiroptical spectroscopic methods for stereochemical characterization of natural products. AB - This review covers conformational and configurational assignments in natural product molecules using chiroptical spectroscopy reported over the last 15 years. Special attention is given to vibrational optical activity methods associated with quantum mechanical calculations. PMID- 26140549 TI - 5'- vs. 3'-end sugar conformational control in shaping up dinucleotides. AB - The 5'-end N-sugar puckering is currently believed to govern the intramolecular dinucleotide stacking. We demonstrate that if this 5'-conformation is indeed important in shaping up dinucleotide structures, the 3'-end sugar conformation can either potentiate or cancel the stacking capacity induced by the 5'-end N sugar conformation. PMID- 26140550 TI - Alternative aluminum-based cocatalysts for the iron-catalyzed oligomerization of ethylene. AB - Multinuclear aluminum cocatalysts have been obtained by the reaction of various phenols, alcohols or diols with trimethylaluminum and were used in situ or as isolated, well-defined species, for the activation of an iron(ii) or an iron(iii) pre-catalyst for the oligomerization of ethylene. The best cocatalyst candidate involves 2,2'-biphenol () in a /AlMe3 ratio of 2/3. PMID- 26140551 TI - A longitudinal investigation of repressive coping and ageing. AB - OBJECTIVES: Two studies investigated the possibility that repressive coping is more prevalent in older adults and that this represents a developmental progression rather than a cohort effect. Study 1 examined repressive coping and mental health cross-sectionally in young and old adults. Study 2 examined whether there was a developmental progression of repressive coping prevalence rates in a longitudinal sample of older adults. METHOD: Study 1 compared younger adults (mean age 27.6 years) with older adults (mean age 74.2 years) on inventories of mental health and well-being and examined the prevalence of repressive coping in both samples. Study 2 re-tested a sample of older adults previously reported following an interval of 7 years. RESULTS AND CONCLUSION: Study 1 - in line with previous research older adults demonstrated greater psychological well-being and had a higher prevalence of repressive coping than younger adults (at 30% vs. 12% respectively). Study 2 - the data indicated that the prevalence of repressive coping rose from 41% at the first time of testing (2002) to 56.4% at the second testing interval (2009). These results suggest that repressive coping may increase across the lifespan in certain individuals and continue to increase throughout older adulthood. Furthermore, this increase in repressive coping with age appears to result in better well-being in those older adults who become repressive copers. PMID- 26140553 TI - Insertion of intercostal chest drains: who, where and when? PMID- 26140554 TI - How clinical managers (can) improve the health service. PMID- 26140556 TI - Medical and oncological management of malignant mesothelioma. AB - Mesothelioma is an aggressive cancer, for which no curative oncological treatment currently exists. This article outlines the options for managing malignant pleural effusions, describes the developments in chemotherapy over the past 10 years and summarizes the evidence for prophylactic and palliative radiotherapy. PMID- 26140557 TI - Cheyne-Stokes respiration during sleep: mechanisms and potential interventions. AB - Cheyne-Stokes respiration is characterized by a typical waxing and waning pattern in breathing amplitude, interspersed with central apnoeas or hypopnoeas. This article reviews current knowledge regarding Cheyne-Stokes respiration with a particular emphasis on the mechanisms and latest methods of intervention. PMID- 26140558 TI - Recognition and management of children with protracted bacterial bronchitis. AB - Chronic moist cough in children can be associated with serious pathologies. Protracted bacterial bronchitis remains a clinical diagnosis causing persistent moist cough, disturbed sleep, exercise intolerance and significant levels of morbidity. Management involves minimal investigations and prolonged courses of antibiotics. PMID- 26140559 TI - Fitness to practise procedures for medical students. AB - Medical students who exhibit severe forms of adverse behaviour (including criminal matters), sometimes accompanied by mental health problems, are likely to be seen by their medical school's fitness to practise committee, a topic explained in this review. PMID- 26140560 TI - Early phase cancer clinical trials: design, ethics and future directions. AB - The main role of early phase clinical trials in cancer is to determine the dose to take forward for future clinical study. However, study design is changing in order to account for the change in focus of drug development toward molecularly targeted agents. PMID- 26140561 TI - Undergraduate and foundation training in trauma and orthopaedics: junior doctors have their say. AB - Undergraduate education in musculoskeletal health is currently insufficient in most medical schools worldwide, in both basic sciences and clinical training. A national survey was carried out to obtain views of current doctors from various specialties about undergraduate and foundation training in trauma and orthopaedics. PMID- 26140562 TI - From medical doctor to medical director: leadership style matters. AB - Leadership is a skill to be developed by all doctors from the foundation trainee to the director of the board. This article explores the impact of leadership style on performance and considers techniques to develop doctors' leadership skills and personal effectiveness. PMID- 26140563 TI - War surgery 100 years ago. PMID- 26140564 TI - Congenital extrahepatic portosystemic shunt. PMID- 26140565 TI - A rare disease presenting as pyrexia, hepatosplenomegaly and pancytopenia. PMID- 26140566 TI - Spontaneous rupture of the urinary bladder. PMID- 26140567 TI - Flipping the instructor in medical teaching. PMID- 26140569 TI - Should critically ill adults be transferred or retrieved? PMID- 26140570 TI - Secondary prevention of stroke. PMID- 26140571 TI - Management of atrial fibrillation: recommendations from NICE. PMID- 26140572 TI - Diagnosis and management of patent foramen ovale. PMID- 26140573 TI - Preinjury Physical Function and Frailty in Injured Older Adults: Self- Versus Proxy Responses. AB - OBJECTIVES: To determine the extent to which proxy respondents can provide reliable reports. DESIGN: Prospective cohort study. SETTING: Level I trauma center. PARTICIPANTS: Seventy-seven older adults (>=65, median 73.0, interquartile range 67-80; 53% female) admitted to three services (trauma, geriatrics, orthopedics) with primary injury diagnoses over a 6-month period and their proxies (43% spouses, 44% children, 5% siblings, 8% friends or other relatives). MEASUREMENTS: Three brief screening instruments (Vulnerable Elders Survey-13 (VES-13), modified Barthel Index (mBI), Life Space Assessment (LSA)) for physical function and frailty were administered to older adults and their proxies within 48 hours of admission. Data analysis included frequencies, percentages, intraclass correlations, and Kappa statistics. RESULTS: Approximately 47% (n = 36) of the proxies lived with the older adults. Perfect agreement and 90% agreement between older adults and proxies: There was perfect agreement for 39 (51%) dyads and a difference of 1 or less (range 1-10) for 66 (86%) on the VES-13, perfect agreement for 48 (62%) and a difference of two or less (range 0-20) for 69 (89%) on the mBI, and perfect agreement for 27 (35%) and a difference of 12 or less (range 0-120) for 55 (71%) on the LSA. CONCLUSION: Proxy reports of older adults' preinjury physical function and frailty are in an acceptable range of agreement with those of the older adults. Using proxy reports when people cannot provide information on themselves may facilitate care management and goal setting. PMID- 26140574 TI - Simplified multi-element analysis of ground and instant coffees by ICP-OES and FAAS. AB - A simplified alternative to the wet digestion sample preparation procedure for roasted ground and instant coffees has been developed and validated for the determination of different elements by inductively coupled plasma optical emission spectrometry (ICP-OES) (Al, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sr, Zn) and flame atomic absorption spectrometry (FAAS) (Ca, Fe, K, Mg, Na). The proposed procedure, i.e. the ultrasound-assisted solubilisation in aqua regia, is quite fast and simple, requires minimal use of reagents, and demonstrated good analytical performance, i.e. accuracy from -4.7% to 1.9%, precision within 0.5 8.6% and recovery in the range 93.5-103%. Detection limits of elements were from 0.086 ng ml(-1) (Sr) to 40 ng ml(-1) (Fe). A preliminary classification of 18 samples of ground and instant coffees was successfully made based on concentrations of selected elements and using principal component analysis and hierarchic cluster analysis. PMID- 26140577 TI - Geropathology Research Network Symposium 2015. PMID- 26140576 TI - Noninvasive screening for intracranial hypertension in children with acute, severe traumatic brain injury. AB - OBJECT: The aim of this study was to determine the relationship between transcranial Doppler (TCD) derived pulsatility index (PI), end diastolic flow velocity (Vd), and intracranial pressure (ICP). The subjects in this study were 36 children admitted after severe traumatic brain injury (TBI) (postresuscitation Glasgow Coma Scale <= 8) undergoing invasive ICP monitoring. METHODS: Subjects underwent a total of 148 TCD studies. TCD measurements of systolic flow velocity (Vs), Vd, and mean flow velocity (Vm) were performed on the middle cerebral artery (MCA) ipsilateral to the ICP monitor. The PI was calculated by the TCD software (Vs-Vd/Vm). ICP registrations were made in parallel with TCD measurements. RESULTS: Using a PI threshold of 1.3, postinjury Day 0-1 PI had 100% sensitivity and 82% specificity at predicting an ICP >= 20 mm Hg (n = 8). During this time frame, a moderately strong relationship was observed between the MCA PI and actual ICP (r = 0.611, p = 0.01). When using a threshold of < 25 cm/sec, postinjury Day 0-1 Vd had a 56% sensitivity to predict an ICP >= 20 mm Hg. Beyond the initial 24 hours from injury, the sensitivity of an MCA PI of 1.3 to detect an ICP >= 20 mm Hg was 47%, and a weak relationship between actual ICP values and MCA PI (r = 0.376, p = 0.01) and MCA Vd (r = -0.284, p = 0.01) was found. CONCLUSIONS: Postinjury Day 0-1 MCA PI > 1.3 has good sensitivity and specificity at predicting an ICP >= 20 mm Hg. In those children with TBI who initially do not meet clear criteria for invasive ICP monitoring but who are at risk for development of intracranial hypertension, TCD may be used as a noninvasive tool to screen for the development of elevated ICP in the first 24 hours following injury. PMID- 26140578 TI - [Effects of Behaviour-oriented Exercise Interventions as Supplement within Structured Health-care Programmes for Diabetes Mellitus Type 2 - A Quasi experimental Multicentre Intervention Study]. AB - Exercise programs do not belong to standard treatment within disease management programmes for diabetes mellitus type 2, up to now. For these reason the effects of a 10-week behaviour-oriented exercise programme have been evaluated focusing on change in activity behaviour and health-related qualitiy of life. 202 patients took part in the investigation. There were significant inbetween group differences in some aspects of the outcome parameters. The study presents useful information on how to modify existing DMPs successfully for improving patient treatment. PMID- 26140579 TI - Caesarean Sections in Beijing, China - Results from a Descriptive Study. AB - OBJECTIVE: Caesarean section rates are increasing dramatically in China. The predominant contributor to the increase in China was the unnecessary Caesarean section. The objective of this study was to estimate the excess economic burden caused by unnecessary Caesarean sections vs. vaginal delivery for Beijing and all China. METHODS: The 33 476 obstetric medical case files from randomly selected 17 hospitals of Beijing in 2011 were taken for our descriptive approach. Based on the individual medical files and on a definition of what necessary and unnecessary Caesarean sections are, we sampled also the data for costs and length of stay for comparisons with vaginal deliveries. The Mann-Whitney U test and Pearson chi-square test statistics were used to test for significant difference in the analysis. RESULTS: The Caesarean section rate was 58.5% among all deliveries and that rate of unnecessary Caesarean sections was 71.5% among all the Caesarean sections but 41.8% among all deliveries in Beijing. The hospitalisation expenses of unnecessary Caesarean sections were 472 US$ higher than that of a vaginal delivery on average. The total excess economic burden caused by unnecessary Caesarean sections can be estimated to 38.97 million US$ for Beijing and to 3.29 billion US$ all over China in 2011. This is equivalent to the annual health expenditure of over 139 575 residents in Beijing and of 11 783 120 residents in China, respectively. CONCLUSION: Socio-economic factors are possible reasons for the increase of unnecessary Caesarean section in China and more analytical attention should be paid to that problem in order to propose fitting practical reactions. PMID- 26140580 TI - [Soliciting Job Centre Clients for a Cardiopreventive Health Examination Programme]. AB - Aim: There is limited knowledge about the reaching of socioeconomic disadvantaged groups for prevention measures. Results of proactive contacting are presented for a 2-step cardiopreventive health examination programme (CHP) in 2 job centres in Northern Germany. Methods: The duration of the programme extended over a period of 10 weeks. All clients aged between 40 and 65 years were included. Phase 1consisted of a self-administered computer-based assessment, and if medical staff were present, blood pressure measurement and/or blood samples were taken. Participants without a history of cardiovascular diseases, interventional/surgical blood vessel procedures, diabetes and a body-mass-index <=35 kg/m2 were invited to a specialised examination centre (phase 2). Logistic regression analysis was used to test predictors for participation in both phases. Variables were age, gender and for phase 2 the distance between participants' residence addresses and the address of the examination centre, cardiovascular risk factors, subjective health and socio-demographics. Results: 344 of the 1 049 invited job centre clients participated in the assessment. Women were more likely to participate than men. A number of 253 participants were invited for blood pressure measurement and blood sample taking. Participation of 209 persons was positively associated with age. A number of 138 participated in phase 2. Participation decreased with increasing distance between the participant's residence address and the address of the examination centre. Smokers, persons with less than 10 years of schooling and those who did not report an elevated level of blood lipids were less likely to participate. Conclusion: Blood pressure measurements and taking of blood samples in job centres were found to be highly accepted. The burden on potential participants to reach preventive measures should be minimised. PMID- 26140581 TI - Thin Versus Thick Description: Analyzing Representations of People and Their Life Worlds in the Literature of Communication Sciences and Disorders. AB - PURPOSE: Evidence-based practice relies on clinicians to translate research evidence for individual clients. This study, the initial phase of a broader research project, examines the textual resources of such translations by analyzing how people with acquired cognitive-communication disorders (ACCD) and their life worlds have been represented in Communication Sciences and Disorders (CSD) research articles. METHOD: Using textual analysis, we completed a categorical analysis of 6,059 articles published between 1936 and 2012, coding for genre, population, and any evidence of thick representations of people and their life worlds, and a discourse analysis of representations used in 56 ACCD research articles, identifying thin and thick representations in 4 domains (derived from the International Classification of Functioning, Disability, and Health) and across article sections. RESULTS: The categorical analysis identified a higher percentage of ACCD articles with some evidence of thick representation (30%) compared with all CSD articles (12%) sampled. However, discourse analysis of ACCD research articles found that thick representations were quite limited; 34/56 articles had thin representational profiles, 19/56 had mixed profiles, and 3/56 had thick profiles. CONCLUSIONS: These findings document the dominance of thin representations in the CSD literature, which we suggest makes translational work more difficult. How clinicians translate such evidence will be addressed in the next research phase, an interview study of speech-language pathologists. PMID- 26140583 TI - Geminin is Essential to Prevent DNA Re-Replication-Dependent Apoptosis in Pluripotent Cells, but not in Differentiated Cells. AB - Geminin is a dual-function protein unique to multicellular animals with roles in modulating gene expression and preventing DNA re-replication. Here, we show that geminin is essential at the beginning of mammalian development to prevent DNA re replication in pluripotent cells, exemplified by embryonic stem cells, as they undergo self-renewal and differentiation. Embryonic stem cells, embryonic fibroblasts, and immortalized fibroblasts were characterized before and after geminin was depleted either by gene ablation or siRNA. Depletion of geminin under conditions that promote either self-renewal or differentiation rapidly induced DNA re-replication, followed by DNA damage, then a DNA damage response, and finally apoptosis. Once differentiation had occurred, geminin was no longer essential for viability, although it continued to contribute to preventing DNA re replication induced DNA damage. No relationship was detected between expression of geminin and genes associated with either pluripotency or differentiation. Thus, the primary role of geminin at the beginning of mammalian development is to prevent DNA re-replication-dependent apoptosis, a role previously believed essential only in cancer cells. These results suggest that regulation of gene expression by geminin occurs only after pluripotent cells differentiate into cells in which geminin is not essential for viability. PMID- 26140582 TI - Fonsecaea pedrosoi-induced Th17-cell differentiation in mice is fostered by Dectin-2 and suppressed by Mincle recognition. AB - Chromoblastomycosis is a chronic skin infection caused by the pigmented saprophytic mould Fonsecaea pedrosoi. Chronicity of infection can be broken by a coordinated innate recognition of the spores by pattern recognition receptors. While Mincle signaling via the Syk/Card9 pathway is required for fungal recognition by host cells, it is not sufficient for host control. Exogenously applied TLR agonists are necessary to promote the induction of proinflammatory cytokines and clearance of infection in vivo. Here, we investigated whether costimulation by TLR agonists fosters the development of adaptive immune responses, by examining the development of fungus-specific T cells. Subcutaneous infection of mice with F. pedrosoi spores induced the activation, expansion, and differentiation of Ag-specific CD4(+) T cells but TLR costimulation did not further augment these T-cell responses. The Dectin-2/FcRgamma/Card9 signaling pathway promoted the differentiation of fungus-specific CD4(+) T cells into Th17 cells, whereas Mincle inhibited the development of this T-helper subset in infected mice. These results indicate differential roles for Dectin-2 and Mincle in the generation of adaptive immune responses to F. pedrosoi infection. PMID- 26140584 TI - Semi-automated hippocampal segmentation in people with cognitive impairment using an age appropriate template for registration. AB - BACKGROUND: To evaluate a new semi-automated segmentation method for calculating hippocampal volumes and to compare results with standard software tools in a cohort of people with subjective memory complaints (SMC) and mild cognitive impairment (MCI). METHODS: Data from 58 participants, 39 with SMC (17 male, 22 female, mean age 72.6) and 19 with MCI (6 male, 13 female, mean age 74.3), were analyzed. For each participant, T1-weighted images were acquired using an MPRAGE sequence on a 3 Tesla MRI system. Hippocampal volumes (left, right, and total) were calculated with a new, age appropriate registration template, based on older people and using the advanced software tool ANTs (Advanced Normalization Tools). The results were compared with manual tracing (seen as the reference standard) and two widely accepted automated software tools (FSL, FreeSurfer). RESULTS: The hippocampal volumes, calculated by using the age appropriate registration template were significantly (P < 0.05) more accurate (mean volume accuracy more than 90%) than those obtained with FreeSurfer and FSL (both less than 70%). Dice coefficients for the hippocampal segmentations with the new template method (75.3%) were slightly, but significantly (P < 0.05) higher than those from FreeSurfer (72.4%). CONCLUSION: These results suggest that an age appropriate registration template might be a more accurate alternative to calculate hippocampal volumes when manual segmentation is not feasible. PMID- 26140585 TI - The Emerging Postdoc Culture in China. AB - Recent years have witnessed tremendous growth in investment toward building a strong scientific research base in China. Though the postdoctoral system in China was started 30 years ago, efforts to foster research there in the past few years have spurred on a new crop of scientists to pursue postdoctoral work in China. PMID- 26140586 TI - The Ribofilm as a Concept for Life's Origins. AB - Recent phylogenetic data indicating that the first archaea were methane-producing galvanizes cross-disciplinary evidence supporting the hypothesis that life arose via thermodynamically directed events at hydrothermal vents. The new developments lead us to propose the concept of a ribofilm in which RNA's origin-of-life role is more akin to a slowly changing platform than a spontaneous self-replicator. PMID- 26140587 TI - From Prescription to Transcription: Genome Sequence as Drug Target. AB - Personalizing treatments to account for genetically mediated differences in drug responses is an exciting opportunity to improve patient outcomes. In this issue, Soccio et al. reveal new mechanisms by which non-coding variants alter the activity of the anti-diabetic drug rosiglitazone. PMID- 26140588 TI - AIMing 2 Curtail Cancer. AB - The dysregulation of the relationship between gut microbiota and innate immune homeostasis can lead to a range of complex diseases. In this issue, Man et al. reveal that the intracellular innate sensor AIM2 regulates microbial and stem cell homeostasis in the gut to protect against colorectal cancer. PMID- 26140589 TI - Brain Wiring in the Fourth Dimension. AB - In this issue of Cell, Langen et al. use time-lapse multiphoton microscopy to show how Drosophila photoreceptor growth cones find their targets. Based on the observed dynamics, they develop a simple developmental algorithm recapitulating the highly complex connectivity pattern of these neurons, suggesting a basic framework for establishing wiring specificity. PMID- 26140590 TI - The Convergence of Systems and Reductionist Approaches in Complex Trait Analysis. AB - Research into the genetic and environmental factors behind complex trait variation has traditionally been segregated into distinct scientific camps. The reductionist approach aims to decrypt phenotypic variability bit by bit, founded on the underlying hypothesis that genome-to-phenome relations are largely constructed from the additive effects of their molecular players. In contrast, the systems approach aims to examine large-scale interactions of many components simultaneously, on the premise that interactions in gene networks can be both linear and non-linear. Both approaches are complementary, and they are becoming increasingly intertwined due to developments in gene editing tools, omics technologies, and population resources. Together, these strategies are beginning to drive the next era in complex trait research, paving the way to improve agriculture and toward more personalized medicine. PMID- 26140591 TI - Genetic Variation Determines PPARgamma Function and Anti-diabetic Drug Response In Vivo. AB - SNPs affecting disease risk often reside in non-coding genomic regions. Here, we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPARgamma, a nuclear receptor for anti-diabetic drugs. Many such SNPs alter binding motifs for PPARgamma or cooperating factors and functionally regulate nearby genes whose expression is strain selective and imbalanced in heterozygous F1 mice. Moreover, genetically determined binding of PPARgamma accounts for mouse strain-specific transcriptional effects of TZD drugs, providing proof of concept for personalized medicine related to nuclear receptor genomic occupancy. In human fat, motif-altering SNPs cause differential PPARgamma binding, provide a molecular mechanism for some expression quantitative trait loci, and are risk factors for dysmetabolic traits in genome-wide association studies. One PPARgamma motif-altering SNP is associated with HDL levels and other metabolic syndrome parameters. Thus, natural genetic variation in PPARgamma genomic occupancy determines individual disease risk and drug response. PMID- 26140592 TI - Single-Molecule Imaging Reveals that Argonaute Reshapes the Binding Properties of Its Nucleic Acid Guides. AB - Argonaute proteins repress gene expression and defend against foreign nucleic acids using short RNAs or DNAs to specify the correct target RNA or DNA sequence. We have developed single-molecule methods to analyze target binding and cleavage mediated by the Argonaute:guide complex, RISC. We find that both eukaryotic and prokaryotic Argonaute proteins reshape the fundamental properties of RNA:RNA, RNA:DNA, and DNA:DNA hybridization-a small RNA or DNA bound to Argonaute as a guide no longer follows the well-established rules by which oligonucleotides find, bind, and dissociate from complementary nucleic acid sequences. Argonautes distinguish substrates from targets with similar complementarity. Mouse AGO2, for example, binds tighter to miRNA targets than its RNAi cleavage product, even though the cleaved product contains more base pairs. By re-writing the rules for nucleic acid hybridization, Argonautes allow oligonucleotides to serve as specificity determinants with thermodynamic and kinetic properties more typical of RNA-binding proteins than of RNA or DNA. PMID- 26140593 TI - A Dynamic Search Process Underlies MicroRNA Targeting. AB - Argonaute proteins play a central role in mediating post-transcriptional gene regulation by microRNAs (miRNAs). Argonautes use the nucleotide sequences in miRNAs as guides for identifying target messenger RNAs for repression. Here, we used single-molecule FRET to directly visualize how human Argonaute-2 (Ago2) searches for and identifies target sites in RNAs complementary to its miRNA guide. Our results suggest that Ago2 initially scans for target sites with complementarity to nucleotides 2-4 of the miRNA. This initial transient interaction propagates into a stable association when target complementarity extends to nucleotides 2-8. This stepwise recognition process is coupled to lateral diffusion of Ago2 along the target RNA, which promotes the target search by enhancing the retention of Ago2 on the RNA. The combined results reveal the mechanisms that Argonaute likely uses to efficiently identify miRNA target sites within the vast and dynamic agglomeration of RNA molecules in the living cell. PMID- 26140594 TI - Neural Representations of Unconditioned Stimuli in Basolateral Amygdala Mediate Innate and Learned Responses. AB - Stimuli that possess inherently rewarding or aversive qualities elicit emotional responses and also induce learning by imparting valence upon neutral sensory cues. Evidence has accumulated implicating the amygdala as a critical structure in mediating these processes. We have developed a genetic strategy to identify the representations of rewarding and aversive unconditioned stimuli (USs) in the basolateral amygdala (BLA) and have examined their role in innate and learned responses. Activation of an ensemble of US-responsive cells in the BLA elicits innate physiological and behavioral responses of different valence. Activation of this US ensemble can also reinforce appetitive and aversive learning when paired with differing neutral stimuli. Moreover, we establish that the activation of US responsive cells in the BLA is necessary for the expression of a conditioned response. Neural representations of conditioned and unconditioned stimuli therefore ultimately connect to US-responsive cells in the BLA to elicit both innate and learned responses. PMID- 26140595 TI - A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer. AB - KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint abrogating Chk1- and MK2 inhibitors, specifically in KRAS- and BRAF-driven cells. Mechanistically, we show that KRAS-mutant cancer displays intrinsic genotoxic stress, leading to tonic Chk1- and MK2 activity. We demonstrate that simultaneous Chk1- and MK2 inhibition leads to mitotic catastrophe in KRAS-mutant cells. This actionable synergistic interaction is validated using xenograft models, as well as distinct Kras- or Braf-driven autochthonous murine cancer models. Lastly, we show that combined checkpoint inhibition induces apoptotic cell death in KRAS- or BRAF-mutant tumor cells directly isolated from patients. These results strongly recommend simultaneous Chk1- and MK2 inhibition as a therapeutic strategy for the treatment of KRAS- or BRAF-driven cancers. PMID- 26140596 TI - Anti-HA Glycoforms Drive B Cell Affinity Selection and Determine Influenza Vaccine Efficacy. AB - Protective vaccines elicit high-affinity, neutralizing antibodies by selection of somatically hypermutated B cell antigen receptors (BCR) on immune complexes (ICs). This implicates Fc-Fc receptor (FcR) interactions in affinity maturation, which, in turn, are determined by IgG subclass and Fc glycan composition within ICs. Trivalent influenza virus vaccination elicited regulation of anti hemagglutinin (HA) IgG subclass and Fc glycans, with abundance of sialylated Fc glycans (sFc) predicting quality of vaccine response. We show that sFcs drive BCR affinity selection by binding the Type-II FcR CD23, thus upregulating the inhibitory FcgammaRIIB on activated B cells. This elevates the threshold requirement for BCR signaling, resulting in B cell selection for higher affinity BCR. Immunization with sFc HA ICs elicited protective, high-affinity IgGs against the conserved stalk of the HA. These results reveal a novel, endogenous pathway for affinity maturation that can be exploited for eliciting high-affinity, broadly neutralizing antibodies through immunization with sialylated immune complexes. PMID- 26140597 TI - Monoclonal 1- and 3-Phosphohistidine Antibodies: New Tools to Study Histidine Phosphorylation. AB - Histidine phosphorylation (pHis) is well studied in bacteria; however, its role in mammalian signaling remains largely unexplored due to the lack of pHis specific antibodies and the lability of the phosphoramidate (P-N) bond. Both imidazole nitrogens can be phosphorylated, forming 1-phosphohistidine (1-pHis) or 3-phosphohistidine (3-pHis). We have developed monoclonal antibodies (mAbs) that specifically recognize 1-pHis or 3-pHis; they do not cross-react with phosphotyrosine or the other pHis isomer. Assays based on the isomer-specific autophosphorylation of NME1 and phosphoglycerate mutase were used with immunoblotting and sequencing IgG variable domains to screen, select, and characterize anti-1-pHis and anti-3-pHis mAbs. Their sequence independence was determined by blotting synthetic peptide arrays, and they have been tested for immunofluorescence staining and immunoaffinity purification, leading to putative identification of pHis-containing proteins. These reagents should be broadly useful for identification of pHis substrates and functional study of pHis using a variety of immunological, proteomic, and biological assays. PMID- 26140599 TI - SnapShot: Motile Cilia. PMID- 26140598 TI - Quantifying Protein-mRNA Interactions in Single Live Cells. AB - Specific binding proteins are crucial for the correct spatiotemporal expression of mRNA. To understand this process, a method is required to characterize RNA protein interactions in single living cells with subcellular resolution. We combined endogenous single RNA and protein detection with two-photon fluorescence fluctuation analysis to measure the average number of proteins bound to mRNA at specific locations within live cells. We applied this to quantify the known binding of zipcode binding protein 1 (ZBP1) and ribosomes to beta-actin mRNA within subcellular compartments of primary fibroblasts and neurons. ZBP1-mRNA binding did not occur in nuclei, contrary to previous conclusions. ZBP1 interaction with beta-actin mRNA was enhanced perinuclearly in neurons compared to fibroblasts. Cytoplasmic ZBP1 and ribosome binding to the mRNA were anti correlated depending on their location in the cell. These measurements support a mechanism whereby ZBP1 inhibits translation of localizing mRNA until its release from the mRNA peripherally, allowing ribosome binding. PMID- 26140600 TI - Direct Reprogramming of RESTing Astrocytes. AB - Understanding the mechanisms underlying neuronal fate determination will provide important insights into brain development and regenerative approaches to neurological diseases. Now in Cell Stem Cell, Masserdotti et al. (2015) use neuronal conversion of astrocytes to dissect transcriptional mechanisms of fate determination and identify circuits that mediate cellular identity. PMID- 26140601 TI - Aspp1: A Guardian of Hematopoietic Stem Cell Integrity. AB - Eliminating hematopoietic stem cells (HSCs) with DNA damage is necessary to maintain the homeostasis of HSCs, but the mechanisms underlying this apoptotic elimination are unclear. Now in Cell Stem Cell, Yamashita et al. (2015) show that Aspp1 coordinates with p53 to protect HSC pool integrity, guarding against hematological malignancies. PMID- 26140602 TI - Back to 2D Culture for Ground State of Intestinal Stem Cells. AB - Generating highly uniform clonogenic stem cell populations has been remarkably difficult with stem cells from human small and large intestine. A recent report by Wang et al. (2015) demonstrated homogeneous expansion of human fetal intestinal stem cells, providing a new culture system to understand self-renewing mechanisms of intestinal stem cells. PMID- 26140603 TI - From Dish to Bedside: Lessons Learned While Translating Findings from a Stem Cell Model of Disease to a Clinical Trial. AB - While iPSCs have created unprecedented opportunities for drug discovery, there remains uncertainty concerning the path to the clinic for candidate therapeutics discovered with their use. Here we share lessons that we learned, and believe are generalizable to similar efforts, while taking a discovery made using iPSCs into a clinical trial. PMID- 26140604 TI - Stem Cell Therapies in Clinical Trials: Progress and Challenges. AB - Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types. To date, there have been few reports of safety issues arising from autologous or allogeneic transplants. Many cells administered show transient presence for a few days with trophic influences on immune or inflammatory responses. Limbal stem cells have been registered as a product for eye burns in Europe and mesenchymal stem cells have been approved for pediatric graft versus host disease in Canada and New Zealand. Many other applications are progressing in trials, some with early benefits to patients. PMID- 26140605 TI - TPO-Induced Metabolic Reprogramming Drives Liver Metastasis of Colorectal Cancer CD110+ Tumor-Initiating Cells. AB - Liver metastasis is a leading cause of death in patients with colorectal cancer. We previously found that colorectal cancer tumor-initiating cells (TICs) expressing CD110, the thrombopoietin (TPO)-binding receptor, mediate liver metastasis. Here, we show that TPO promotes metastasis of CD110+ TICs to the liver by activating lysine degradation. Lysine catabolism generates acetyl-CoA, which is used in p300-dependent LRP6 acetylation. This triggers tyrosine phosphorylation of LRP6, ultimately activating Wnt signaling to promote self renewal of CD110+ TICs. Lysine catabolism also generates glutamate, which modulates the redox status of CD110+ TICs to promote liver colonization and drug resistance. Mechanistically, TPO-mediated induction of c-myc orchestrates recruitment of chromatin modifiers to regulate metabolic gene expression. Our findings, therefore, establish TPO as a component of the physiological environment critical for metastasis of colorectal cancer to the liver. PMID- 26140606 TI - Quantification of Retinogenesis in 3D Cultures Reveals Epigenetic Memory and Higher Efficiency in iPSCs Derived from Rod Photoreceptors. AB - Cell-based therapies to treat retinal degeneration are now being tested in clinical trials. However, it is not known whether the source of stem cells is important for the production of differentiated cells suitable for transplantation. To test this, we generated induced pluripotent stem cells (iPSCs) from murine rod photoreceptors (r-iPSCs) and scored their ability to make retinae by using a standardized quantitative protocol called STEM-RET. We discovered that r-iPSCs more efficiently produced differentiated retinae than did embryonic stem cells (ESCs) or fibroblast-derived iPSCs (f-iPSCs). Retinae derived from f-iPSCs had fewer amacrine cells and other inner nuclear layer cells. Integrated epigenetic analysis showed that DNA methylation contributes to the defects in f-iPSC retinogenesis and that rod-specific CTCF insulator protein binding sites may promote r-iPSC retinogenesis. Together, our data suggest that the source of stem cells is important for producing retinal neurons in three dimensional (3D) organ cultures. PMID- 26140607 TI - Prospects of beta-Secretase Inhibitors for the Treatment of Alzheimer's Disease. AB - beta-Secretase continues to be an attractive drug discovery target for the therapeutic intervention of Alzheimer's disease (AD). This enzyme plays a critical role in the production of neurotoxic beta-amyloid (Abeta) peptides in the brain. Over the years, extensive research efforts have led to the development of many promising classes of inhibitors against this protease. Many small molecule, peptidomimetic, and nonpeptide beta-secretase inhibitors have now overcome the key challenging development hurdles such as selectivity and brain penetration. A number of inhibitors have also shown further promise in reducing brain Abeta and rescuing cognitive decline in animal models. Recently, several beta-secretase inhibitors have entered into preclinical and phase I studies, and at least one of these inhibitors has advanced to phase II/III human trials. The outlook on beta-secretase inhibitor drugs for the treatment of AD patients is discussed herein. PMID- 26140608 TI - Does it help that efficacy has been proven once we start discussing (added) benefit? AB - Since the introduction of benefit assessment to support reimbursement decisions in Germany there seems to be the impression that totally distinct methodology and strategies for decision making would apply in the field of drug licensing and reimbursement. In this article, the position is held that, while decisions may differ due to differing mandates of drug licensing and reimbursement bodies, the underlying strategies are quite similar. For this purpose, we briefly summarize the legal basis for decision making in both fields from a methodological point of view, and review two recent decisions about reimbursement regarding grounds for approval. We comment on two examples, where decision making was based on the same pivotal studies in the licensing and reimbursement process. We conclude that strategies in the field of reimbursement are (from a methodological standpoint) until now more liberal than established rules in the field of drug licensing, but apply the same principles. Formal proof of efficacy preceding benefit assessment can thus be understood as a gatekeeper against principally wrong decision making about efficacy and risks of new drugs in full recognition that more is needed. We elaborate on the differences between formal proof of efficacy on the one hand and the assessment of benefit/risk or added benefit on the other hand, because it is important for statisticians to understand the difference between the two approaches. PMID- 26140609 TI - Flow-through omental flap to free anterolateral thigh flap for complex chest wall reconstruction: Case report and review of the literature. AB - Despite the options currently available for chest wall reconstruction, patients with complex composite defects may still pose a significant challenge for the reconstructive surgeon when only using conventional methods. In particular, prior radiotherapy and/or large en bloc resection may leave inadequate regional flaps and recipient vessels for free tissue transfer. Here, we describe a case in which we reconstruct a 14 cm * 18 cm complex chest wall defect, secondary to tumor resection and infected sternum debridement, with a pedicled flow-through omental flap to a 14 cm * 22 cm free anterolateral thigh flap using the omental gastroepiploic vessels as recipient vessels. Reconstruction was successful with excellent flap viability, and no complications at recipient or donor sites. We review the literature on complex chest wall reconstruction and introduce this valuable option of utilizing a pedicled omental flap as a flow-through flap to a free flap for patients without viable recipient vessels or local flaps. PMID- 26140610 TI - Tocilizumab for steroid refractory acute graft-versus-host disease. AB - Acute graft-versus-host-disease (aGVHD) is a frequent and often lethal complication of allogeneic hematopoietic stem cell transplant despite prophylaxis. Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody that has evidence of activity in patients with steroid refractory (SR) GVHD. We retrospectively report on nine patients with grade 3 or 4 SR aGVHD who received tocilizumab. Eight mg/kg of tocilizumab was administered intravenously every 3-4 weeks. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 48 years. Five patients had alternate donor sources. Median time from aGVHD onset to tocilizumab administration was 44 days. Two patients had complete responses and two had partial responses. Median survival from start of tocilizumab was 26 days (range 13-1054). Our limited experience demonstrated an overall response rate of 44% (CR + PR); however, this response was not durable. Further studies are needed to determine the optimal time for tocilizumab initiation. PMID- 26140611 TI - Crack-Photolithography for Membrane-Free Diffusion-Based Micro/Nanofluidic Devices. AB - Recent advances in controlling the cracking phenomena established a novel unconventional fabrication technique to generate mixed-scale patterns/structures with resolution and accuracy comparable to conventional nanofabrication techniques. Here, we adapt our previous cracking-assisted nanofabrication technique (called "crack-photolithography") relying on only the standard photolithography to develop micro/nanofluidic devices with greatly reduced time and cost. The crack-photolithography makes it possible not only to simultaneously produce micropatterns and nanopatterns with various dimensions but also to replicate both of the mixed-scale patterns in a high-throughput manner. Therefore, a microfluidic channel network can easily be fabricated with a nanochannel array that can function as a nanoporous membrane wherever necessary, which basically plays a key role in diffusion-allowed but convection-suppressed microfluidic devices. In addition, the nanochannel array can manipulate the transport of small molecules by adjusting its dimension and/or number at will, so that nanochannel-array-integrated micro/nanofluidic devices prove even more robust and accurate in diffusion control than conventional membrane-integrated microfluidic devices. As an application of such micro/nanofluidic devices, we employed synthetic bacterial cells and found that their genetic induction and expression are dominated by extracellular diffusive microenvironments that were completely engineered using the nanochannel array. Hence, the crack photolithography could provide innovative fabrication techniques for unprecedented micro/nanofluidic devices that show substantial potential for a wide range of biological and chemical applications. PMID- 26140613 TI - In Situ Microfocus Chemical Computed Tomography of the Composition of a Single Catalyst Particle During Hydrogenation of Nitrobenzene in the Liquid Phase. AB - Heterogeneous catalysis performed in the liquid phase is an important type of catalytic process which is rarely studied in situ. Using microfocus X-ray fluorescence and X-ray diffraction computed tomography (MU-XRF-CT, MU-XRD-CT) in combination with X-ray absorption near-edge spectroscopy (XANES), we have determined the active state of a Mo-promoted Pt/C catalyst (NanoSelect) for the liquid-phase hydrogenation of nitrobenzene under standard operating conditions. First, MU-XRF-CT and MU-XRD-CT reveal the active state of Pt catalyst to be reduced, noncrystalline, and evenly dispersed across the support surface. Second, imaging of the Pt and Mo distribution reveals they are highly stable on the support and not prone to leaching during the reaction. This study demonstrates the ability of chemical computed tomography to image the nature and spatial distribution of catalysts under reaction conditions. PMID- 26140614 TI - Human unrestricted somatic stem cells loaded in nanofibrous PCL scaffold and their healing effect on skin defects. AB - Unrestricted somatic stem cells (USSCs) loaded in nanofibrous polycaprolactone (PCL) scaffolds can be used for skin regeneration when grafted onto full thickness skin defects of rats. Nanofibrous PCL scaffolds were designed by the electrospinning method and crosslinked with laminin protein. Afterwards, the scaffolds were evaluated by scanning electron microscopy, and physical and mechanical assays. In this study, nanofibrous PCL scaffolds loaded with USSCs were grafted onto the skin defects. The wounds were subsequently investigated 21 days after grafting. Results of mechanical and physical analyses showed good resilience and compliance to movement as a skin graft. In animal models; study samples exhibited the most pronounced effect on wound closure, with statistically significant improvement in wound healing being seen at 21 days post-operatively. Histological examinations of healed wounds from all samples showed a thin epidermis plus recovered skin appendages in the dermal layer for samples with cell. Thus, the graft of nanofibrous PCL scaffolds loaded with USSC showed better results during the healing process of skin defects in rat models. PMID- 26140615 TI - RNA interference technology with emphasis on delivery vehicles-prospects and limitations. AB - CONTEXT: RNA interference (RNAi)-based therapeutics rely upon safe and efficient delivery of small interfering RNA (siRNA) molecules. OBJECTIVE: This review explores various dimensions of RNAi with emphasis on the development of nanoparticle-based delivery vectors for safe and efficient siRNA delivery. METHODS: An exhaustive database search has been done regarding studies done to investigate the potential of siRNA delivery employing nanoparticles has been cited in the present review. RESULTS AND CONCLUSION: With the current challenges, there is a need for collaborative work allowing for the successful development of nanoparticle/siRNA complexes as health-promoting biotherapeutics. PMID- 26140616 TI - Electrophoretic mobility of oil droplets in electrolyte and surfactant solutions. AB - Electrophoretic mobility of oil droplets of micron sizes in PBS and ionic surfactant solutions was measured in this paper. The experimental results show that, in addition to the applied electric field, the speed and the direction of electrophoretic motion of oil droplets depend on the surfactant concentration and on if the droplet is in negatively charged SDS solutions or in positively charged hexadecyltrimethylammonium bromide (CTAB) solutions. The absolute value of the electrophoretic mobility increases with increased surfactant concentration before the surfactant concentration reaches to the CMC. It was also found that there are two vortices around the oil droplet under the applied electric field. The size of the vortices changes with the surfactant and with the electric field. The vortices around the droplet directly affect the drag of the flow field to the droplet motion and should be considered in the studies of electrophoretic mobility of oil droplets. The existence of the vortices will also influence the determination and the interpretation of the zeta potential of the oil droplets based on the measured mobility data. PMID- 26140612 TI - Plasmofluidics: Merging Light and Fluids at the Micro-/Nanoscale. AB - Plasmofluidics is the synergistic integration of plasmonics and micro/nanofluidics in devices and applications in order to enhance performance. There has been significant progress in the emerging field of plasmofluidics in recent years. By utilizing the capability of plasmonics to manipulate light at the nanoscale, combined with the unique optical properties of fluids and precise manipulation via micro/nanofluidics, plasmofluidic technologies enable innovations in lab-on-a-chip systems, reconfigurable photonic devices, optical sensing, imaging, and spectroscopy. In this review article, the most recent advances in plasmofluidics are examined and categorized into plasmon-enhanced functionalities in microfluidics and microfluidics-enhanced plasmonic devices. The former focuses on plasmonic manipulations of fluids, bubbles, particles, biological cells, and molecules at the micro/nanoscale. The latter includes technological advances that apply microfluidic principles to enable reconfigurable plasmonic devices and performance-enhanced plasmonic sensors. The article is concluded with perspectives on the upcoming challenges, opportunities, and possible future directions of the emerging field of plasmofluidics. PMID- 26140617 TI - A Versatile Approach to CF3 -Containing 2-Pyrrolidones by Tandem Michael Addition Cyclization: Exemplification in the Synthesis of Amidine Class BACE1 Inhibitors. AB - The synthesis of new fluorinated pyrrolidones starting from unprotected amino esters and amino nitriles through a Michael addition-lactamization sequence is described. The resulting CF3 -containing building blocks, bearing a quaternary stereogenic center adjacent to the fluorinated group, have been converted into amino pyrrolidines that display potent beta-secretase 1 (BACE1) inhibitory activity. This work constitutes an example of selective fluorination as a valid strategy for the modulation of physicochemical and biological properties of lead compounds in drug discovery. PMID- 26140619 TI - S-Doping of an Fe/N/C ORR Catalyst for Polymer Electrolyte Membrane Fuel Cells with High Power Density. AB - Fe/N/C is a promising non-Pt electrocatalyst for the oxygen reduction reaction (ORR), but its catalytic activity is considerably inferior to that of Pt in acidic medium, the environment of polymer electrolyte membrane fuel cells (PEMFCs). An improved Fe/N/C catalyst (denoted as Fe/N/C-SCN) derived from Fe(SCN)3, poly-m-phenylenediamine, and carbon black is presented. The advantage of using Fe(SCN)3 as iron source is that the obtained catalyst has a high level of S doping and high surface area, and thus exhibits excellent ORR activity (23 A g(-1) at 0.80 V) in 0.1 M H2SO4 solution. When the Fe/N/C-SCN was applied in a PEMFC as cathode catalyst, the maximal power density could exceed 1 W cm(-2). PMID- 26140618 TI - Arterial structure and function in vascular ageing: are you as old as your arteries? AB - Advancing age may be the most potent independent predictor of future cardiovascular events, a relationship that is not fully explained by time-related changes in traditional cardiovascular risk factors. Since some arteries exhibit differential susceptibility to atherosclerosis, generalisations regarding the impact of ageing in humans may be overly simplistic, whereas in vivo assessment of arterial function and health provide direct insight. Coronary and peripheral (conduit, resistance and skin) arteries demonstrate a gradual, age-related impairment in vascular function that is likely to be related to a reduction in endothelium-derived nitric oxide bioavailability and/or increased production of vasoconstrictors (e.g. endothelin-1). Increased exposure and impaired ability for defence mechanisms to resist oxidative stress and inflammation, but also cellular senescence processes, may contribute to age-related changes in vascular function and health. Arteries also undergo structural changes as they age. Gradual thickening of the arterial wall, changes in wall content (i.e. less elastin, advanced glycation end-products) and increase in conduit artery diameter are observed with older age and occur similarly in central and peripheral arteries. These changes in structure have important interactive effects on artery function, with increases in small and large arterial stiffness representing a characteristic change with older age. Importantly, direct measures of arterial function and structure predict future cardiovascular events, independent of age or other cardiovascular risk factors. Taken together, and given the differential susceptibility of arteries to atherosclerosis in humans, direct measurement of arterial function and health may help to distinguish between biological and chronological age-related change in arterial health in humans. PMID- 26140622 TI - Cu Vacancies Boost Cation Exchange Reactions in Copper Selenide Nanocrystals. AB - We have investigated cation exchange reactions in copper selenide nanocrystals using two different divalent ions as guest cations (Zn(2+) and Cd(2+)) and comparing the reactivity of close to stoichiometric (that is, Cu2Se) nanocrystals with that of nonstoichiometric (Cu(2-x)Se) nanocrystals, to gain insights into the mechanism of cation exchange at the nanoscale. We have found that the presence of a large density of copper vacancies significantly accelerated the exchange process at room temperature and corroborated vacancy diffusion as one of the main drivers in these reactions. Partially exchanged samples exhibited Janus like heterostructures made of immiscible domains sharing epitaxial interfaces. No alloy or core-shell structures were observed. The role of phosphines, like tri-n octylphosphine, in these reactions, is multifaceted: besides acting as selective solvating ligands for Cu(+) ions exiting the nanoparticles during exchange, they also enable anion diffusion, by extracting an appreciable amount of selenium to the solution phase, which may further promote the exchange process. In reactions run at a higher temperature (150 degrees C), copper vacancies were quickly eliminated from the nanocrystals and major differences in Cu stoichiometries, as well as in reactivities, between the initial Cu2Se and Cu(2-x)Se samples were rapidly smoothed out. These experiments indicate that cation exchange, under the specific conditions of this work, is more efficient at room temperature than at higher temperature. PMID- 26140623 TI - Effects of Molecular Oxygen, Solvent, and Light on Iridium-Photoredox/Nickel Dual Catalyzed Cross-Coupling Reactions. AB - In order to achieve reproducibility during iridium-photoredox and nickel dual catalyzed sp(3)-sp(2) carbon-carbon bond-forming reactions, we investigated the role that molecular oxygen (O2), solvent and light-source (CF lamp or blue LED) play in a variety of Ir-photoredox mediated transformations. The presence of O2 was discovered to be important for catalyst activation when air-stable Ni(II) precatalysts were used in DMF under CF lamp irradiation; however, O2 was not required for catalysis when conducted with Ni(COD)2 in the same reaction system. O2 is believed to promote rapid reduction of the Ni(II) precatalyst by Ir(II) to Ni(0). In addition to O2, the effects that solvent and light-source have on the dual-catalyzed decarboxylative cross-coupling reactions will be discussed. These findings have enabled us to develop a more robust dual-catalyzed decarboxylative cross-coupling protocol. PMID- 26140624 TI - [Not Available]. PMID- 26140625 TI - [The Gradual Formation of the Concept of 'Light Quanta']. AB - The Gradual Formation of the Concept of 'Light Quanta'. The complex concept of 'light quanta' which made its first appearance in Albert Einstein's 1905 paper on a "heuristic point of view" to cope with the photoelectric effect and other forms of interaction of light and matter, has a rich history both before and after 1905. Some of its semantic layers lead as far back as Newton and Kepler, others are only fully espoused several decades later, yet others initially increased, then diminished in importance and finally vanished. Two historiographic approaches are discussed and exemplified: a) my own model of conceptual development as a series of semantic accretions, and b) Mark Turner's model of 'conceptual blending'. Both of these models are shown to be useful and will be further explored in my own efforts to come to grips with the complex process of concept formation. PMID- 26140626 TI - [The Origin of Scientific Notions in the Circle of the Roman Accademiadella Virt3/4 around 1550]. AB - The Origin of Scientific Notions in the Circle of the Roman Accademia della Virtu around 1550. Between c. 1537 and 1555 a group of humanists, clerics, architects and philologists known as the so-called Accademia della Virtu got together in Rome to work on a program which was formulated in a letter by the Sienese humanist Claudio Tolomei in 1542 and published in 1547. Starting out with the intention to understand the only surviving antique book on architecture and architectural theory - Vitruvius' De architectura libri decem - the program describes a series of 24 books, eleven containing the classical text and its translation with commentaries, 13 books systematically illustrating and documenting all known and available material remains from Roman antiquity. This program for a scientific classical archaeology in a modern sense was not only intended to serve the intellectual curiosity of some humanist antiquarians but to help architects and their patrons to develop a new architecture of the same high quality as the idealized Roman examples. To achieve this practical as well as theoretical goal it was obviously necessary to re-create the antique vocabulary of architecture and its rules as well as to unify the contemporary usage of notions and norms in a canon. The first results of this project seem to be the In decem Libros M. Vitruvii Pollionis de Architectura Annotationes by Guillaume Philandrier (Rome, 1544) - up to this day a very valuable explanation of ambiguous parts in the Vitruvian text. Until the 1980s, it was believed that this book was the only outcome of the ambitious project; but then two codices of drawings after antique reliefs were identified as preparations for one of the other 23 volumes - and, because of their systematic approach, regarded as the 'first systematic archaeological book'. Now it seems that there are some other corpora of manuscripts and drawings documenting antique artifacts that should be regarded as results of the Accademia's work, too, showing antique buildings, inscriptions and coins. Other results of the unfinished project may be the theoretical and practical works of the two most influencial architects of the sixteenth century: Jacopo Barozzi da Vignola and Andrea Palladio. PMID- 26140627 TI - ["Chemistry of Concepts"and "Historical Sense". On Philosophical Concept Formation]. AB - "Chemistry of Concepts" and "Historical Sense". On Philosophical Concept Formation. The question concerning concepts and their relations to objects and words has had a long and controversial history. Recently, it is challenged by an anew turn towards objects and an emphasized object-oriented ontology. The article argues that one reason for this is the reduction of concepts towards pure rational constructions and offers arguments for alternative understandings. In this context, the article proposes a re-reading of Nietzsche's particular approach and shows that Nietzsche's thought is decisively shaped by the sciences of his time, especially physiology and chemistry. Before the background of the recent increase in research interest on Nietzsche and the sciences the article examines place and function of the sciences related to the genealogy and justification of concepts. Opposing a strong naturalist reading it makes a plea for understanding Nietzsche's epistemological critique concerning concepts systematically as a triple one: philological, physiological, and historical. PMID- 26140628 TI - [The Significance of Terminology for the Idea of a Historical Period- Considerations on Fruhe Neuzeit/Early Modern]. AB - The Significance of Terminology for the Idea of a Historical Period - Considerations on Fruhe Neuzeit/Early Modern. This article focuses on the relationship between the names given to historical periods and the attributed substance of that period. It argues that the possibility of a neutralisation in terms of substantive meaning depends on the terminology used to delineate a historical period. Considering the example of 'early modern history' the article sketches the usage of that term in twentieth century historiography. While it is clear that the concept cannot escape the inherent teleology of modernity succeeding pre-modern ages, the analysis shows that historians have used 'early modern' in surprisingly divers ways trying to overcome the semantic meaning of the term itself. PMID- 26140629 TI - Measuring Cumulative Exposure to Oxygen with a Diphenylphosphine-Alkyl Naphthaleneimide Luminescence Turn-On Dyad. AB - 2-(2-Diphenylphosphanylethyl)benzo[de]isoquinoline-1,3-dione is a poorly luminescent, photoinduced-electron-transfer (PET) dyad, NI-(Ph)2 P:, in which the luminescence of its naphthaleneimide (NI) part is quenched by the lone-pair electrons of the phosphorus atom of the (Ph)2 P: group. Photoinduced oxidation of (Ph)2 P: to (Ph)2 P=O by molecular oxygen regenerates the luminescence of the NI group, because the oxidized form (Ph)2 P=O does not serve as a quencher to the NI system. The oxidation of (Ph)2 P: is thermally inaccessible. The NI-(Ph)2 P: system was applied to monitoring the cumulative exposure of oxidation-sensitive goods to molecular oxygen. The major advantage of this new PET system is that it reacts with oxygen only via the photoinduced channel, which offers the flexibility of monitoring the cumulative exposure to oxygen in different time periods, simply by varying the sampling frequency. Electronic-energy calculations and optical spectroscopic data revealed that the luminescence turn-on upon reaction with molecular oxygen relies on a PET mechanism. PMID- 26140630 TI - Fecal microbiota transplantation - something more than merely a therapeutic curiosity. PMID- 26140631 TI - Initial experience with fecal microbiota transplantation in Clostridium difficile infection - transplant protocol and preliminary results. AB - BACKGROUND AND AIMS: Clostridium difficile infection (CDI) constitutes an important cause of antibiotic-associated diarrhea. Recurrence after first-line treatment with antibiotics is high and fecal microbiota transplantation (FMT) may be effective for refractory and recurrent CDI. This series aims to describe the efficacy of FMT in the treatment of refractory and recurrent CDI. METHODS: A prospectively recorded single-centre case series of patients with persistent or recurrent CDI treated with FMT between June 2014 and March 2015 was analyzed. Primary and secondary outcomes were defined as resolution of diarrhea without recurrence of CDI within 2 months after one or more FMT, respectively. A descriptive analysis was performed. RESULTS: 8 FMT were performed in 6 patients, 3 with refractory CDI and 3 with recurrent CDI. The median age of recipients was 71 years and 66.7% were women. One FMT was delivered through colonoscopy and the remaining 87.5% through esophagogastroduodenoscopy. One upper FMT was excluded due to recurrence of CDI after antibiotic exposure for a respiratory infection. The overall cure rate of FMT was total with lower route and 83.3% with upper route. Primary cure rate was achieved in 83.3% of patients and secondary cure rate was achieved in all patients. Median time to resolution of diarrhea after FMT was 1 day and no complications were reported during follow-up. CONCLUSION: FMT appears to constitute a safe and effective approach in the management of refractory and recurrent CDI. Difference between primary and secondary cure rates may result of insufficient restoration of intestinal microbiota with a single FMT. PMID- 26140632 TI - Esophagogastric pathology in morbid obese patient: Preoperative diagnosis, influence in the selection of surgical technique. AB - INTRODUCTION: Given the difficulty in accessing to the excluded stomach after gastric bypass and the increase in gastroesophageal reflux after sleeve gastrectomy, it is justified to perform a preoperative fibrogastroscopy.The influence of the fibrogastroscopy (FGS) findings in the therapeutic approach is analyzed. PATIENTS AND METHODS: A retrospective study of preoperative FGS findings is performed, from 04/06 to 12/12. The influence of the FGS results on the surgical technique selection, in the endoscopic or medical treatment and its relation to gastric fistula is analyzed by means of multivariate regression (confounding factors: Age, body mass index, arterial hypertension, diabetes mellitus, antiplatelet therapy, surgical technique (bariatric surgery, sleeve gastrectomy). RESULTS: Three hundred thirty one patients are included: 32.6% biopsy of gastric lesion; 27% gastritis; 18.1% hiatal hernia; 3% metaplasia; 0.6% Barrett esophagus; 2.1% esophagitis; 0.3% dysplasia; 0.3 Schatzky´s ring; 1.5% incompetent cardia; 2.4% duodenitis; 0.3% gastric erosions; 0.6% gastric xanthoma; 1.8%, gastric polyp; 1.6% duodenal ulcer; 0.6% papulo-erosive gastritis; 0.6% esophageal papilloma; 0.3% submucosal tumor. Helicobacter pylori+ 30.2% (triple therapy eradication in all patients). The FGS findings led to a variation in the surgical technique or to the completion of endoscopic treatment in 22.2% of cases.The gastric lesions did not influence the development of gastric fistula. Independent prognostic factors of fistula: Sleeve gastrectomy (7.9% vs. 2.7%; p = 0.02; OR: 1.38 IC95: 1.01-1.87) and the body mass index > 50 kg/m2) (6.7% vs. 2.2%; p = 0.04; OR: 3.7 IC95: 1.12-12.4). CONCLUSIONS: The diagnosis of gastroesophageal disease through preoperative FGS motivated variations in the therapeutic approach in 52% of patients, so we consider essential to include the preoperative FGS in bariatric surgery. PMID- 26140633 TI - Different mechanisms of actions of genistein, quercetin on spontaneous contractions of rabbit duodenum. AB - Flavonoids are known to relax precontracted intestinal smooth muscle and delay intestinal transit or intestinal peristalsis. The aim of this study was to determine the effects of genistein and quercetin on spontaneous contractions of rabbit duodenum in vitro in an organ bath. Genistein and quercetin (0.1-10uM) reduced the amplitude of spontaneous contractions in the longitudinal and circular smooth muscle of rabbit duodenum, but they did not modify the frequency. Bay K8644 (L-type Ca2+ channel activator), apamin, charybdotoxin, and tetraetylammonium (K+ channel blockers) reverted the inhibition of amplitude of spontaneous contractions induced by genistein in longitudinal and circular smooth muscle. H-89 (protein kinase A inhibitor) antagonized the reduction of the amplitude of spontaneous contractions induced by quercetin in longitudinal and circular smooth muscle of duodenum, while 2,5-dideoxiadenosine (adenylyl cyclase inhibitor) reverted only the reduction of the amplitude in circular smooth muscle. In conclusion, genistein and quercetin reduce the spontaneous contractions in the duodenum by different mechanisms of actions. The effect of genistein would be mediated by Ca2+ and K+ channels, while the effect of quercetin would be mediated by cAMP and protein kinase A. PMID- 26140634 TI - Implication of the presence of a variant hepatic artery during the Whipple procedure. AB - INTRODUCTION: The anatomical variants of the hepatic artery may have important implications for pancreatic cancer surgery. The aim of our study is to compare the outcome following a pancreatoduodenectomy (PD) in patients with or without a variant hepatic artery arising from superior mesenteric artery. MATERIAL AND METHODS: We reviewed 151 patients with periampullary tumoral pathology. All patients underwent oncological PD between January 2005 and February 2012. Our series was divided into two groups: Group A: Patients with a hepatic artery arising from superior mesenteric artery; and Group B: Patients without a hepatic artery arising from superior mesenteric artery. We expressed the results as mean +/- standard deviation for continuous variables and percentages for qualitative variables. Statistical tests were considered significant if p < 0.05. RESULTS: We identified 11 patients with a hepatic artery arising from superior mesenteric artery (7.3%). The most frequent variant was an aberrant right hepatic artery (n = 7), following by the accessory right hepatic artery (n = 2) and the common hepatic artery trunk arising from the superior mesenteric artery (n = 2). In 73% of cases the diagnosis of the variant was intraoperative. R0 resection was performed in all patients with a hepatic artery arising from superior mesenteric artery. There were no significant differences in the tumor resection margins and the incidence of postoperative complications. CONCLUSION: Oncological PD is feasible by the presence of a hepatic artery arising from superior mesenteric artery. The complexity of having it does not seem to influence in tumor resection margins, complications and survival. PMID- 26140635 TI - The potential usefulness of human leukocyte antigen typing for celiac disease screening: A systematic review and meta-analysis. AB - BACKGROUND AND AIM: The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but the real contribution of its typing for screening is still uncertain. We aim to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. METHODS: Systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease were selected. MEDLINE and EMBASE were searched from 1st January 2004 until 31st December 2013. Two independent researchers carried out selection and classification of studies, data extraction and analysis. Meta-analysis combining sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease were carried out. RESULTS: 6 studies including 1303 individuals were finally evaluated. Pooled sensitivity was 98% (95% confidence interval: 97-99). Overall specificity was 45% (95% confidence interval: 41-48). Regarding specificity, studies were heterogeneous and a subgroup analysis was done according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09). CONCLUSIONS: Due to its great sensitivity and low negative likelihood ratio, human leukocyte antigen-DQ2/DQ8 typing would be an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population. PMID- 26140636 TI - [Submucosal chromoendoscopy. A technique that highlights epithelia and differentiates histological components, and renders colon polypectomy easier and safer]. AB - Submucosal chromoendoscopy involves the injection of a solution containing a vital stain, usually indigo carmine, into the intestinal wall submucosal layer. This allows to: Better delimit and characterize the various epithelia present (colonic mucosa, adenoma, hyperplastic polyp, serrated polyp, small bowel mucosa); expose and delimit lesion implantation areas; cooperate in the lifting of resectable lesions; ensure section across the submucosal plane; identify intestinal wall structures; render complex polypectomy feasible; and facilitate the identification of perforations.The present paper offers information on the endoscopic technique for submucosal injection, solution preparation and concentration, and on the potential benefits it may provide for polypectomy or endocopic mucosal resection whether en block or piecemeal. This endoscopic technique simultaneously combines a diagnostic and a therapeutic aspect, since lesion lifting in association with better delimited contours may improve not only accuracy but also endoscopic resection safety and feasibility. PMID- 26140637 TI - Gastric metastasis originating from an adenocarcinoma of the endometrium. PMID- 26140638 TI - Coexistence of Kaposi sarcoma and gastric diffuse large B-cell lymphoma in a HIV infected patient. PMID- 26140639 TI - Taenia saginata: An imported case. PMID- 26140640 TI - Usefulness of magnifying endoscopy with narrow-band imaging for identification of early gastric cancer around an ulcer scar. PMID- 26140641 TI - Long segments of columnar-lined lower esophagus are not always metaplastic. AB - The presence of columnar epithelium in the esophagus is associated with two conditions: Barrett's esophagus and heterotopic gastric mucosa. The former results from the metaplastic replacement of the normal distal squamous esophageal lining, is associated with gastroesophageal reflux and is a pre-neoplastic condition. The second is thought as a congenital condition, resulting from the incomplete squamous epithelialization of the esophagus during embryologic development. It is found mainly in the cervical esophagus. Histologically, Barrett's esophagus is composed of an admixture of cardiac mucosa, oxintocardiac mucosa and intestinal metaplasia. Most of heterotopic gastric mucosa consists of oxynticmucosa where the mucosal glands are straight and composed of parietal and chief cells.There are few reports of heterotopic gastric mucosa in the lower esophagus, generally presenting as small islands. In the present report, a series of four cases of large lower esophageal heterotopic gastric mucosa is described. All patients were initially misdiagnosed with Barrett's esophagus and referred for surveillance. The correct diagnosis was based in endoscopic and histological features. In all, a circular tiny strip of squamous mucosa was observed at endoscopy between the lower end of the columnarlined esophagus and the esophagogastric junction, defined as the proximal end of the gastric folds. Biopsy samples taken from the columnar-lined segments of the four patients showed pure oxyntic mucosa.When columnar-lined esophagus is observed in the distal esophagus not in continuity with gastric mucosa, the diagnosis of heterotopic gastric mucosa must be thought and confirmed histologically by the presence of pure oxyntic mucosa. PMID- 26140642 TI - Endoluminal brachytherapy in the treatment of oesophageal cancer. Technique description, case report and review of the literature. AB - Endoesophageal brachytherapy is a useful technique for the palliative treatment of dysphagia in advanced oesophageal cancer. This technique offers good results on dysphagia control and quality of life.We report the case of a patient treated with this technique presenting complete response to the dysphagia. We describe endoesophageal brachyterapy technique and we comment on the literature. PMID- 26140643 TI - [Biological drugs in inflammatory bowel disease: Management and care]. PMID- 26140644 TI - Emphysematous gastritis associated with portal venous gas: Medical management to an infrequent acute abdominal pain. PMID- 26140645 TI - Pneumoperitoneum after CT colonography in a patient with ulcerative colitis. PMID- 26140646 TI - Leiomyosarcoma of the inferior vena cava: Feasibility of surgical resection. A report of two cases. PMID- 26140647 TI - Hepatocellular carcinoma with bile duct invasion presenting as acute cholangitis. PMID- 26140648 TI - Stump appendicitis. Underrated reality? PMID- 26140649 TI - Gastroesophageal reflux disease and dental erosion correlation; a new theory from ancient time. PMID- 26140650 TI - Survey on the use of capsule endoscopy for patients with known or suspected Crohn's disease in Spain. PMID- 26140651 TI - Oesophageal dysphagia as a presentation of a gastric duplication cyst of the cardia. PMID- 26140653 TI - Use of eriochrome cyanine R for routine histology and histopathology: an improved dichromatic staining procedure. AB - A modified dichromatic iron-eriocyanine R (Fe-ECR) staining method is described. Staining obtained with this new technique generally was similar to that of hematoxylin and eosin (H & E). Cell nuclei were stained blue. Cardiac, smooth and skeletal muscle, and red blood cells, were stained different shades of red. Collagen fibers were stained different shades of orange, usually faintly. Decalcified bony tissue was stained pinkish violet. Epithelial cells were strongly stained deep shades of red, magenta and violet. Cartilage matrix, and goblet and mast cells were unstained. Although Fe-ECR staining differed too much from standard H & E staining to be a substitute for diagnostic purposes, the dichromatic method described might usefully replace van Gieson or trichrome stains, especially if muscle is of interest. A pH 0.95 staining solution was used to differentiate initially over-stained sections followed by washing in distilled water. This dichromatic technique is easier to perform and more precisely controllable than other ECR dichromatic methods. The entire procedure can be completed in less than 5 min. The technique has the advantages of greater technical simplicity and speed, a larger range of polychromasia, and a longer shelf-life than H & E. ECR also is more reliably available than hematoxylin and usually is less expensive. PMID- 26140652 TI - Utility of the Child Behavior Checklist as a Screener for Autism Spectrum Disorder. AB - The Child Behavior Checklist (CBCL) has been proposed for screening of autism spectrum disorders (ASD) in clinical settings. Given the already widespread use of the CBCL, this could have great implications for clinical practice. This study examined the utility of CBCL profiles in differentiating children with ASD from children with other clinical disorders. Participants were 226 children with ASD and 163 children with attention-deficit/hyperactivity disorder, intellectual disability, language disorders, or emotional disorders, aged 2-13 years. Diagnosis was based on comprehensive clinical evaluation including well-validated diagnostic instruments for ASD and cognitive testing. Discriminative validity of CBCL profiles proposed for ASD screening was examined with area under the curve (AUC) scores, sensitivity, and specificity. The CBCL profiles showed low discriminative accuracy for ASD (AUC 0.59-0.70). Meeting cutoffs proposed for ASD was associated with general emotional/behavioral problems (EBP; mood problems/aggressive behavior), both in children with and without ASD. Cutoff adjustment depending on EBP-level was associated with improved discriminative accuracy for school-age children. However, the rate of false positives remained high in children with clinical levels of EBP. The results indicate that use of the CBCL profiles for ASD-specific screening would likely result in a large number of misclassifications. Although taking EBP-level into account was associated with improved discriminative accuracy for ASD, acceptable specificity could only be achieved for school-age children with below clinical levels of EBP. Further research should explore the potential of using the EBP adjustment strategy to improve the screening efficiency of other more ASD-specific instruments. PMID- 26140654 TI - Use of eriochrome cyanine R in routine histology and histopathology: is it time to say goodbye to hematoxylin? AB - Eriochrome cyanine R (ECR) is a synthetic anionic dye that forms complexes with cations such as iron. We found that an iron-ECR (Fe-ECR) mixture provided either nuclear or myelin staining depending on the differentiator used. Selective nuclear staining was obtained by differentiation in an aqueous HCl solution, pH 0.95, followed by a wash in slightly alkaline tap water; the pH difference facilitated control of differentiation. When used with an eosin B counterstain, results were nearly indistinguishable from standard hematoxylin and eosin (H & E) staining. Nuclear staining with Fe-ECR provides tinctorial features similar to regressive aluminum-hemateins as well as resistance to acidic solutions such as those of iron hemateins. Fe-ECR also stained selectively intestinal cells of the diffuse neuroendocrine system (DNES). In addition to its use as an H & E substitute, acid differentiated Fe-ECR produced acid-resistant and selective nuclear counterstaining in combination with Alcian blue, and in the Papanicolaou and van Gieson techniques. With alkali differentiation, Fe-ECR produced selective myelin staining, which was compatible with neutral red counterstaining. Myelin sheaths were stained aqua blue. Fe-ECR could be used for both cytological and histological samples, and was suitable for use in automated tissue stainers. ECR also is less expensive than hematoxylin. Hematoxylin still may be preferred as a nuclear counterstain for some immunostaining methods for which Fe-ECR mixtures probably are too acidic. PMID- 26140655 TI - Quantification of alpha-Gal Antigen Removal in the Porcine Dermal Tissue by alpha Galactosidase. AB - The alpha-Gal (Galalpha1,3-Galbeta1-4GlcNAc-R) epitope, the major xenoantigen, is the first barrier in a porcine-to-man tissue and organ xenotransplantation. The elimination or reduction of the alpha-Gal epitopes is therefore an important step for a successful xenotransplantation. The present study is to evaluate the alpha Gal elimination in the porcine skin with alpha-galactosidase treatment, and to assess two methods (immunohistochemistry and inhibition ELISA) that may be used in quality control for quantifying the extent of the alpha-Gal elimination. Enzymatic cleavage in a single-step process is extremely efficient and affordable at eliminating the alpha-Gal epitope even in a tissue as dense as the porcine dermis. The cost of enzymatic cleavage is found to be less than US$7 for a 10 * 10 cm piece of porcine skin (0.5 mm thick) or about US$140 for 100 g of 3 dimensional soft tissues. After enzymatic cleavage, the alpha-Gal-positive immunostaining was essentially undetectable in enzyme-treated porcine skin. The inhibition rate constant of the monoclonal anti-Gal antibody M86 binding to alpha Gal-bovine serum albumin in ELISA was reduced from 15.0 +/- 4.3 (n = 10) to 6.1 +/- 2.6 (n = 7) after enzyme treatment, in comparison to 4.4 +/- 1.8 (n = 9) background inhibition of decellularized human skin (the ultimate negative control), which demonstrates ~ 84% elimination of alpha-Gal epitopes in treated porcine skin. To examine the suitability of two detection methods for the routine quality control application, comparative studies were made with control and enzyme-treated porcine skin, porcine skin from the alpha-Gal knockout animal, as well as decellularized human skin. The data show that the traditional immunohistochemistry and, to a less extent, the inhibition ELISA with further modifications can be used as quality control tools in the production and selection of biocompatible bioprosthetic devices. The biological evaluation of enzyme-treated porcine skin is ongoing with a small animal model and a nonhuman primate model. PMID- 26140656 TI - Comparison of Gene Expression Between Pediatric and Adult Gastric Mucosa with Helicobacter pylori Infection. AB - BACKGROUND: Although Helicobacter pylori infection among adults is a major risk factor for the development of gastric cancer and initial infection with H. pylori may occur before 5 years of age, the direct effects of H. pylori infection since childhood on gastric mucosa are unknown. The aim of this study was to evaluate gene expression in the H. pylori-infected gastric mucosa of children. METHODS: Gastric mucosal samples were obtained from 24 patients (12 adults and 12 children) who had undergone endoscopic evaluation of chronic abdominal complaints and were examined by the adult and pediatric gastroenterologists at Juntendo University Hospital. Six adult and pediatric patients with and six without H. pylori infection were enrolled. Their gastric mucosal samples obtained from the antrum and corpus were used for microarray, real-time polymerase chain reaction, and immunohistochemical analyses to examine the expression of inflammatory carcinogenic molecules. RESULTS: The expression of inflammatory molecules was upregulated in the H. pylori-infected gastric mucosa from both adults and children. The expression of olfactomedin-4 was only upregulated in adult patients, while that of pim-2, regenerating islet-derived 3 alpha, lipocalin-2, and C-X-C motif chemokine ligand 13 was equally upregulated in the infected gastric mucosa of both adults and children. CONCLUSIONS: Because several carcinogenic molecules are upregulated in H. pylori-infected gastric mucosa even in children, early eradication therapy from childhood may be beneficial to decrease the incidence of gastric cancer. Although increased expression of olfactomedin-4 can be important in suppressing gastric cancer in adults, the increase was not detected in children. PMID- 26140657 TI - Voice Changes in Elderly Adults: Prevalence and the Effect of Social, Behavioral, and Health Status on Voice Quality. AB - OBJECTIVES: To estimate the prevalence of dysphonia and the effect of several risk factors on vocal quality in a representative population of older adults. DESIGN: Cross-sectional. SETTING: Korea. PARTICIPANTS: Individuals aged 65 and older who underwent laryngoscopy from 2008 to 2010 (N = 3,759). MEASUREMENTS: The prevalence of dysphonia and the effect of potential risk factors on voice quality in elderly adults were measured. RESULTS: The mean age of participants was 72.4. The prevalence of dysphonia was 8.5% (95% confidence interval (CI) = 7.4-9.8). There was no significant difference in prevalence according to age. Multivariable analysis after adjusting for age, sex, vocal fold disease, and all variables that were identified in the univariate analysis revealed that urban residence (odds ratio (OR) = 1.83, 95% CI = 1.11-3.04), underweight (OR = 2.79, 95% CI = 1.45 5.38) or normal weight (OR = 1.63, 95% CI = 1.03-2.59), poor (OR = 2.00, 95% CI = 1.19-3.34) or intermediate (OR = 2.08, 95% CI = 1.15-3.78) subjective health status, asthma (OR = 2.08, 95% CI = 1.12-3.86), chronic obstructive pulmonary disease (OR = 2.49, 95% CI = 1.10-5.62), thyroid disease (OR = 3.08, 95% CI = 1.50-6.34), and vocal fold disease (OR = 3.72, 95% CI = 2.16-6.42) were independently associated with dysphonia in elderly adults. CONCLUSION: This study provides valuable information regarding the prevalence of dysphonia and the risk factors that contribute to vocal quality in older adults. These factors are mostly associated with social, behavioral, and underlying health status variables. Multidisciplinary treatment should be considered to improve voice conditions in elderly adults. PMID- 26140658 TI - Tobacco smoking and hand eczema - is there an association? AB - BACKGROUND: Numerous risk factors have been suggested for hand eczema. This systematic review evaluates the association between tobacco smoking and hand eczema. OBJECTIVE: To review the literature systematically on the association between smoking and hand eczema. METHODS: The PubMed and EMBASE databases were searched up to 27 January 2015 for articles on the association between tobacco smoking and hand eczema, including human studies in English and German only. Experimental studies, studies on tobacco allergy, case reports, reviews and studies on second-hand smoking were excluded. RESULTS: Twenty articles were included. Among studies in occupational settings, three of seven found a statistically significant positive association between tobacco smoking and hand eczema prevalence rate, as did four of eight population-based studies. The association was stronger for studies in occupational settings than for population based studies. No studies reported tobacco to be a clear protective factor for hand eczema. Two of five studies regarding severity found a positive association between smoking and hand eczema severity. CONCLUSION: Overall, the data indicate that smoking may cause an increased frequency of hand eczema, particularly in high-risk occupations. However, data from studies controlling for other risk factors are conflicting, and few prospective studies are available. Studies controlling for other risk factors are needed, and information regarding the diagnosis of subclasses of hand eczema, as well as severity, may be important. PMID- 26140659 TI - Does gender or mode of HIV acquisition affect virological response to modern antiretroviral therapy (ART)? AB - OBJECTIVES: Previous UK studies have reported disparities in HIV treatment outcomes for women. We investigated whether these differences persist in the modern antiretroviral treatment (ART) era. METHODS: A single-centre cohort analysis was carried out. We included in the study all previously ART-naive individuals at our clinic starting triple ART from 1 January 2006 onwards with at least one follow-up viral load (VL). Time to viral suppression (VS; first viral load < 50 HIV-1 RNA copies/mL), virological failure (VF; first of two consecutive VLs > 200 copies/mL more than 6 months post-ART) and treatment modification were estimated using standard survival methods. RESULTS: Of 1086 individuals, 563 (52%) were men whose risk for HIV acquisition was sex with other men (MSM), 207 (19%) were men whose risk for HIV acquisition was sex with women (MSW) and 316 (29%) were women. Median pre-ART CD4 count and time since HIV diagnosis in these groups were 298, 215 and 219 cells/MUL, and 2.3, 0.3 and 0.3 years, respectively. Time to VS was comparable between groups, but women [adjusted hazard ratio (aHR) 2.32; 95% confidence interval (CI) 1.28-4.22] and MSW (aHR 3.28; 95% CI 1.91 5.64) were at considerably higher risk of VF than MSM. Treatment switches and complete discontinuation were also more common among MSW [aHR 1.38 (95% CI 1.04 1.81) and aHR 1.73 (95% CI 0.97-3.16), respectively] and women [aHR 1.87 (95% CI 1.43-2.46) and aHR 3.20 (95% CI 2.03-5.03), respectively] than MSM. CONCLUSIONS: Although response rates were good in all groups, poorer virological outcomes for women and MSW have persisted into the modern ART era. Factors that might influence the differences include socioeconomic status and mental health disorders. Further interventions to ensure excellent response rates in women and MSW are required. PMID- 26140660 TI - Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison. AB - OBJECTIVE: Benzodiazepines (BZD) are recommended as first-line treatment for status epilepticus (SE), with lorazepam (LZP) and midazolam (MDZ) being the most widely used drugs and part of current treatment guidelines. Clonazepam (CLZ) is also utilized in many countries; however, there is no systematic comparison of these agents for treatment of SE to date. METHODS: We identified all patients treated with CLZ, LZP, or MDZ as a first-line agent from a prospectively collected observational cohort of adult patients treated for SE in four tertiary care centers. Relative efficacies of CLZ, LZP, and MDZ were compared by assessing the risk of developing refractory SE and the number of antiseizure drugs (ASDs) required to control SE. RESULTS: Among 177 patients, 72 patients (40.62%) received CLZ, 82 patients (46.33%) LZP, and 23 (12.99%) MDZ; groups were similar in demographics and SE characteristics. Loading dose was considered insufficient in the majority of cases for LZP, with a similar rate (84%, 95%, and 87.5%) in the centers involved, and CLZ was used as recommended in 52% of patients. After adjustment for relevant variables, LZP was associated with an increased risk of refractoriness as compared to CLZ (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.66-15.5) and with an increased number of ASDs needed for SE control (OR 4.35, 95% CI 1.8-10.49). SIGNIFICANCE: CLZ seems to be an effective alternative to LZP and MDZ. LZP is frequently underdosed in this setting. These findings are highly relevant, since they may impact daily practice. PMID- 26140662 TI - Triptans for Acute Migraine: A Drug Class Review. PMID- 26140661 TI - Dysregulated post-transcriptional control of COX-2 gene expression in gestational diabetic endothelial cells. AB - BACKGROUND AND PURPOSE: Hyperglycaemic memory describes the progression of diabetic complications during subsequent periods of improved glycaemia. We addressed the hypothesis that transient hyperglycaemia causes aberrant COX-2 expression in HUVEC in response to IL-1beta through the induction of long-lasting epigenetic changes involving microRNA-16 (miR-16), a post-transcriptional modulator of COX-2 expression. EXPERIMENTAL APPROACH: Studies were performed on HUVEC collected from women with gestational diabetes mellitus (GDM) (dHUVEC) and normal women (nHUVEC). KEY RESULTS: In dHUVEC treated with IL-1beta, the expression of COX-2 mRNA and protein was enhanced and generation of prostanoids increased (the most abundant was the promitogenic PGF2alpha ). COX-2 mRNA was more stable in dHUVEC and this was associated with miR-16 down-regulation and c Myc induction (a suppressor of miR expression). dHUVEC showed increased proliferation in response to IL-1beta, which was prevented by a COX-2 inhibitor and PGF2alpha receptor antagonist. Comparable changes in COX-2 mRNA, miR-16 and c Myc detected in dHUVEC were produced in nHUVEC exposed to transient high glucose and then stimulated with IL-1beta under physiological glucose levels; superoxide anion production was enhanced under these experimental conditions. CONCLUSIONS AND IMPLICATIONS: Our results describe a possible mechanism operating in GDM that links the enhanced superoxide anion production and epigenetic changes, associated with hyperglycaemic memory, to endothelial dysfunction through dysregulated post transcriptional control of COX-2 gene expression in response to inflammatory stimuli. The association of conventional therapy for glycaemic control with agents affecting inflammatory responses and oxidative stress might lead to a more effective prevention of the complications associated with GDM. PMID- 26140664 TI - 40th FEBS Congress, The Biochemical Basis of Life, Berlin, Germany, July 4-9, 2015. PMID- 26140663 TI - Negative-pressure wound therapy for management of diabetic foot wounds: a review of the mechanism of action, clinical applications, and recent developments. AB - Negative-pressure wound therapy (NPWT) plays an important role in the treatment of complex wounds. Its effect on limb salvage in the management of the diabetic foot is well described in the literature. However, a successful outcome in this subgroup of diabetic patients requires a multidisciplinary approach with careful patient selection, appropriate surgical debridement, targeted antibiotic therapy, and optimization of healing markers. Evolving NPWT technology including instillation therapy, nanocrystalline adjuncts, and portable systems can further improve results if used with correct indications. This review article summarizes current knowledge about the role of NPWT in the management of the diabetic foot and its mode of action, clinical applications, and recent developments. PMID- 26140665 TI - Parent-adolescent relationship in youths with a chronic condition. AB - BACKGROUND: Suffering from a chronic disease or disability (CDD) during adolescence can be a burden for both the adolescents and their parents. The aim of the present study is to assess how living with a CDD during adolescence, the quality of parent-adolescent relationship (PAR) and the adolescent's psychosocial development interact with each other. METHODS: Using the Swiss Multicenter Adolescent Survey on Health 2002 (SMASH02) database, we compared adolescents aged 16-20 years with a CDD (n = 760) with their healthy peers (n = 6493) on sociodemographics, adolescents' general and psychosocial health, interparental relationship and PAR. RESULTS: Bivariate analyses showed that adolescents with a CDD had a poorer psychosocial health and a more difficult relationship with their parents. The log-linear model indirectly linked CDD and poor PAR through four variables: two of the adolescents' psychosocial health variables (suicide attempt and sensation seeking), the need for help regarding difficulties with parents and a highly educated mother that acted as a protective factor, allowing for a better parent-adolescent with a CDD relationship. CONCLUSION: It is essential for health professionals taking care of adolescents with a CDD to distinguish between issues in relation with the CDD from other psychosocial difficulties, in order to help these adolescents and their parents deal with them appropriately and thus maintain a healthy PAR. PMID- 26140666 TI - Review of null hypothesis significance testing in the ophthalmic literature: are most 'significant' P values false positives? AB - P values associated with null hypothesis significance testing (NHST) are almost universal in the ophthalmic literature. A P value < 0.05 is traditionally considered 'significant'. This concept may deflect further thought about the veracity of the results. P values influence the publishability of the data and have flow-on effects for funding success and the direction of future research. Despite their importance, the problems inherent in P values have been recognized since their inception, and in more recent years have been increasingly highlighted in some scientific fields. In this review, we aim to bring the problems associated with P values and NHST to the attention of the ophthalmic research community. We do not offer a universal solution to the problem of determining the veracity of a scientific claim; however, we demonstrate the need for caution in interpreting 'significant' P values by performing a Bayesian re analysis of t-tests in the ophthalmic literature. PMID- 26140667 TI - Neutrophil elastase induces inflammation and pain in mouse knee joints via activation of proteinase-activated receptor-2. AB - BACKGROUND AND PURPOSE: Neutrophil elastase plays a crucial role in arthritis. Here, its potential in triggering joint inflammation and pain was assessed, and whether these effects were mediated by proteinase-activated receptor-2 (PAR2). EXPERIMENTAL APPROACH: Neutrophil elastase (5 MUg) was injected into the knee joints of mice and changes in blood perfusion, leukocyte kinetics and paw withdrawal threshold were assessed. Similar experiments were performed in animals pretreated with the neutrophil elastase inhibitor sivelestat, the PAR2 antagonist GB83, the p44/42 MAPK inhibitor U0126 and in PAR2 receptor knockout (KO) mice. Neutrophil elastase activity was also evaluated in arthritic joints by fluorescent imaging and sivelestat was assessed for anti-inflammatory and analgesic properties. KEY RESULTS: Intra-articular injection of neutrophil elastase caused an increase in blood perfusion, leukocyte kinetics and a decrease in paw withdrawal threshold. Sivelestat treatment suppressed this effect. The PAR2 antagonist GB83 reversed neutrophil elastase-induced synovitis and pain and these responses were also attenuated in PAR2 KO mice. The MAPK inhibitor U0126 also blocked neutrophil elastase-induced inflammation and pain. Active neutrophil elastase was increased in acutely inflamed knees as shown by an activatable fluorescent probe. Sivelestat appeared to reduce neutrophil elastase activity, but had only a moderate anti-inflammatory effect in this model. CONCLUSIONS AND IMPLICATIONS: Neutrophil elastase induced acute inflammation and pain in knee joints of mice. These changes are PAR2-dependent and appear to involve activation of a p44/42 MAPK pathway. Blocking neutrophil elastase, PAR2 and p44/42 MAPK activity can reduce inflammation and pain, suggesting their utility as therapeutic targets. PMID- 26140668 TI - The auxin transporter, OsAUX1, is involved in primary root and root hair elongation and in Cd stress responses in rice (Oryza sativa L.). AB - Auxin and cadmium (Cd) stress play critical roles during root development. There are only a few reports on the mechanisms by which Cd stress influences auxin homeostasis and affects primary root (PR) and lateral root (LR) development, and almost nothing is known about how auxin and Cd interfere with root hair (RH) development. Here, we characterize rice osaux1 mutants that have a longer PR and shorter RHs in hydroponic culture, and that are more sensitive to Cd stress compared to wild-type (Dongjin). OsAUX1 expression in root hair cells is different from that of its paralogous gene, AtAUX1, which is expressed in non hair cells. However, OsAUX1, like AtAUX1, localizes at the plasma membrane and appears to function as an auxin tranporter. Decreased auxin distribution and contents in the osaux1 mutant result in reduction of OsCyCB1;1 expression and shortened PRs, LRs and RHs under Cd stress, but may be rescued by treatment with the membrane-permeable auxin 1-naphthalene acetic acid. Treatment with the auxin transport inhibitors 1-naphthoxyacetic acid and N-1-naphthylphthalamic acid increased the Cd sensitivity of WT rice. Cd contents in the osaux1 mutant were not altered, but reactive oxygen species-mediated damage was enhanced, further increasing the sensitivity of the osaux1 mutant to Cd stress. Taken together, our results indicate that OsAUX1 plays an important role in root development and in responses to Cd stress. PMID- 26140670 TI - Ultrasound stylet for non-image-guided ventricular catheterization. AB - OBJECT Urgent ventriculostomy placement can be a lifesaving procedure in the setting of hydrocephalus or elevated intracranial pressure. While external ventricular drain (EVD) insertion is common, there remains a high rate of suboptimal drain placement. Here, the authors seek to demonstrate the feasibility of an ultrasound-based guidance system that can be inserted into an existing EVD catheter to provide a linear ultrasound trace that guides the user toward the ventricle. METHODS The ultrasound stylet was constructed as a thin metal tube, with dimensions equivalent to standard catheter stylets, bearing a single element, ceramic ultrasound transducer at the tip. Ultrasound backscatter signals from the porcine ventricle were processed by custom electronics to offer real time information about ventricular location relative to the catheter. Data collected from the prototype device were compared with reference measurements obtained using standard clinical ultrasound imaging. RESULTS A study of porcine ventricular catheterization using the experimental device yielded a high rate of successful catheter placement after a single pass (10 of 12 trials), despite the small size of pig ventricles and the lack of prior instruction on porcine ventricular architecture. A characteristic double-peak signal was identified, which originated from ultrasound reflections off of the near and far ventricular walls. Ventricular dimensions, as obtained from the width between peaks, were in agreement with standard ultrasound reference measurements (p < 0.05). Furthermore, linear ultrasound backscatter data permitted in situ measurement of the stylet distance to the ventricular wall (p < 0.05), which assisted in catheter guidance. CONCLUSIONS The authors have demonstrated the ability of the prototype ultrasound stylet to guide ventricular access in the porcine brain. The alternative design of the device makes it potentially easy to integrate into the standard workflow for bedside EVD placement. The availability of a fast, easy-to use, inexpensive guidance system can play a role in reducing the complication rate for EVD placement. PMID- 26140671 TI - Influence of moderate intensity physical activity levels and gender on conditioned pain modulation. AB - This study examined the potential influence of moderate intensity physical activity (PA) levels and gender on central pain modulation using conditioned pain modulation (CPM) in healthy men and women. Twenty four individuals (12 men and 12 women) who reported engaging in the moderate intensity PA for 150 min or more per week and 24 individuals (12 men and 12 women) who reported engaging in moderate intensity PA for 60 min or less per week completed a self-report PA questionnaire and a 7-day PA assessment using an accelerometer. Furthermore, the participants completed the CPM testing to evaluate the efficiency of central pain modulation. The active individuals scored higher on the PA questionnaire and spent more minutes for light, lifestyle, moderate and vigorous intensity PA than the less active individuals. The active men and women exhibited comparable magnitudes of CPM, and showed a greater magnitude of CPM when compared to their less active counterparts. However, these beneficial effects of higher dose moderate intensity PA disappeared when time spent for vigorous intensity PA was statistically controlled for. These results suggest that the higher dose moderate intensity PA does not add to the benefits from vigorous intensity PA to further improve central pain modulatory systems. PMID- 26140669 TI - The Role of Regional Therapies for in-Transit Melanoma in the Era of Improved Systemic Options. AB - The incidence of melanoma has been increasing at a rapid rate, with 4%-11% of all melanoma recurrences presenting as in-transit disease. Treatments for in-transit melanoma of the extremity are varied and include surgical excision, lesional injection, regional techniques and systemic therapies. Excision to clear margins is preferred; however, in cases of widespread disease, this may not be practical. Historically, intralesional therapies were generally not curative and were often used for palliation or as adjuncts to other therapies, but recent advances in oncolytic viruses may change this paradigm. Radiation as a regional therapy can be quite locally toxic and is typically relegated to disease control and symptom relief in patients with limited treatment options. Regional therapies such as isolated limb perfusion and isolated limb infusion are older therapies, but offer the ability to treat bulky disease for curative intent with a high response rate. These techniques have their associated toxicities and can be technically challenging. Historically, systemic therapy with chemotherapies and biochemotherapies were relatively ineffective and highly toxic. With the advent of novel immunotherapeutic and targeted small molecule agents for the treatment of metastatic melanoma, the armamentarium against in-transit disease has expanded. Given the multitude of options, many different combinations and sequences of therapies can be offered to patients with in-transit extremity melanoma in the contemporary era. Reported response and survival rates of the varied treatments may offer valuable information regarding treatment decisions for patients with in-transit melanoma and provide rationale for these decisions. PMID- 26140672 TI - Development and preclinical evaluation of a new galactomannan-based dressing with antioxidant properties for wound healing. AB - We describe a novel wound dressing (HR006) with two components: a lyophilized matrix of the galactomannan from locust bean gum (LBG) and an antioxidant hydration solution (AHsol) containing curcumin and N-acetyl-L-cysteine (NAC). Physico-structural analyses of the LBG matrix revealed homogeneous interconnected pores with high absorbing capacity showing excellent properties for moist wound care (MWC). In an in vitro oxidative stress fibroblast injury model, the AHsol showed relevant protective effects reducing intracellular reactive oxygen species (ROS) production, rescuing cell viability, and regulating expression of inflammation-related genes (COX-2, TNF-alpha, IL-1alpha, IL-1beta). The new dressing showed good biocompatibility profile as demonstrated by cytotoxicity, hemocompatibility, and skin irritation tests. Moreover, in an in vivo skin wound model in pigs, this dressing enhanced the production of healthy and organized granulation tissue and re-epithelization. In summary, HR006 exhibits significant antioxidant activity, good biocompatibility, and excellent repair capabilities improving tissue remodeling and the healing of wounds. PMID- 26140673 TI - Prevalence and Risk Factors of Hypertension in Urban Areas of Cameroon: A Nationwide Population-Based Cross-Sectional Study. AB - Accurate estimates of the prevalence rate of hypertension and determinants in Cameroon are crucial to inform efficient prevention and control policies. The authors carried out a cluster-specific cross-sectional survey in urban areas of the 10 regions of Cameroon to assess the prevalence and risk factors of hypertension in Cameroonian adults using the WHO STEPwise approach to Surveillance (STEPS). Sociodemographic data were collected and blood pressure and glycemia were measured using standardized methods. Participants were adults of both sexes aged 16 years or older. A total of 15,470 participants were surveyed. The age-standardized prevalence rate of hypertension was 29.7%. The awareness rate was 14.1%. Independent correlates of hypertension included higher age, male sex, obesity, hyperglycemia, and living in the Savannah zone. The prevalence of hypertension is high in urban areas of Cameroon, with very low awareness. Prevention and control strategies should emphasize on improvement and vulgarization of population opportunistic screening and education. PMID- 26140675 TI - Enumeration of Somatic and F-RNA Phages as an Indicator of Fecal Contamination in Potable Water from Rural Areas of the North West Province. AB - Bacteriophages are regarded as enteric viral indicators in faecally contaminated water systems and may indicate the presence of human viral pollution. They are relatively resistant to inactivation by natural and treatment processes. In this study, the presence of somatic coliphages and F-RNA coliphages was investigated in potable water from rural areas in the North West province. Water samples were aseptically collected from boreholes and tap water from some rural communities in the North West Province. Physical parameters of the water, such as the temperature, pH and turbidity, were measured before sample collection. Double agar layer assay was performed using ISO, (1995, 2000) standard methods. Bottled water was used as a negative control and the strains fX174 and MS2 as positive controls. Of the 16 water samples collected, 15 were positive for somatic bacteriophages while F-RNA coliphages were detected in only two samples. Amongst the positive samples 189 and three plaque forming units were obtained for both somatic and F-RNA coliphages, respectively. No coliphage was detected in water from Masamane tap 1. The rest of the samples obtained from various rural areas were positive and did not comply with national and international standards for potable water. This was a cause for concern and should be further investigated. PMID- 26140676 TI - Polypyrrole-polyoxometalate/reduced graphene oxide ternary nanohybrids for flexible, all-solid-state supercapacitors. AB - Novel polypyrrole-polyoxometalate/reduced graphene oxide ternary nanohybrids (TNHs) are synthesized via a one-pot redox relay strategy. The TNHs exhibit high areal specific capacitance (2.61 mF cm(-2)), and the fabricated solid device also exhibits good rate capability, excellent flexibility and mechanical stability. PMID- 26140674 TI - Occurrence and Control of Legionella in Recycled Water Systems. AB - Legionella pneumophila is on the United States Environmental Protection Agency (USEPA) Candidate Contaminant list (CCL) as an important pathogen. It is commonly encountered in recycled water and is typically associated with amoeba, notably Naegleria fowleri (also on the CCL) and Acanthamoeba sp. No legionellosis outbreak has been linked to recycled water and it is important for the industry to proactively keep things that way. A review was conducted examine the occurrence of Legionella and its protozoa symbionts in recycled water with the aim of developing a risk management strategy. The review considered the intricate ecological relationships between Legionella and protozoa, methods for detecting both symbionts, and the efficacy of various disinfectants. PMID- 26140677 TI - Lysosome targeting fluorescence probe for imaging intracellular thiols. AB - A BODIPY-based fluorescence turn-on probe, exhibiting high selectivity and sensitivity towards intracellular thiols with excellent lysosomal localization is reported. The probe displayed fast response towards biothiols in aqueous solution. Localization of the probe in lysosome was demonstrated by intracellular colocalization studies with the aid of LysoSensor Green. PMID- 26140678 TI - A target-induced three-way G-quadruplex junction for 17beta-estradiol monitoring with a naked-eye readout. AB - A label-free and enzyme-free three-way G-quadruplex junction sensing system for the amplified detection of 17beta-estradiol has been constructed by the ingenious coupling of split G-quadruplex DNAzyme with toehold-mediated strand displacement. The biosensor is ultrasensitive, enabling the visual detection of 17beta estradiol concentrations as low as 1 fM without instrumentation. PMID- 26140679 TI - Characterizing rhodopsin signaling by EPR spectroscopy: from structure to dynamics. AB - Electron paramagnetic resonance (EPR) spectroscopy, together with spin labeling techniques, has played a major role in the characterization of rhodopsin, the photoreceptor protein and G protein-coupled receptor (GPCR) in rod cells. Two decades ago, these biophysical tools were the first to identify transmembrane helical movements in rhodopsin upon photo-activation, a critical step in the study of GPCR signaling. EPR methods were employed to identify functional loop dynamics within rhodopsin, to measure light-induced millisecond timescale changes in rhodopsin conformation, to characterize the effects of partial agonists on the apoprotein opsin, and to study lipid interactions with rhodopsin. With the emergence of advanced pulsed EPR techniques, the stage was set to determine the amplitude of structural changes in rhodopsin and the dynamics in the rhodopsin signaling complexes. Work in this area has yielded invaluable information about mechanistic properties of GPCRs. Using EPR techniques, receptors are studied in native-like membrane environments and the effects of lipids on conformational equilibria can be explored. This perspective addresses the impact of EPR methods on rhodopsin and GPCR structural biology, highlighting historical discoveries made with spin labeling techniques, and outlining exciting new directions in the field. PMID- 26140680 TI - Two new ent-atisanes from the root of Euphorbia fischeriana Steud. AB - Two new ent-atisanes ent-1beta,3beta,16beta,17-tetrahydroxyatisane (1), ent 1beta,3alpha,16beta,17-tetrahydroxyatisane (2) together with 11 known diterpenes were isolated from the anti-tumour activity fraction of Euphorbia fischeriana Steud. The compounds were identified by detailed spectroscopic analysis, including extensive 2D-NMR experiments. X-ray analysis was applied to determine the structure of compound 2. All 13 compounds were screened for cytotoxicity in vitro against human tumour MCF-7, HepG-2 and SGC-7901 cell lines. Compounds 1 and 2 showed the inhibitory effects against MCF-7 with IC50 levels of 23.21 and 15.42 MUM; simultaneously, compounds 4, 6, 8 and 11 also had definite inhibitory effect against different cell lines. PMID- 26140681 TI - Mechanism for formation of atmospheric Cl atom precursors in the reaction of dinitrogen oxides with HCl/Cl(-) on aqueous films. AB - Nitryl chloride (ClNO2) and nitrosyl chloride (ClNO) are potential sources of highly reactive atmospheric chlorine atoms, hence of much interest, but their formation pathways are unknown. This work predicts production of these nitrogen oxychlorides from ab initio molecular dynamics (AIMD) simulations of N2O5 or an NO2 dimer on the surface of a thin film of water which is struck by gaseous HCl. Both of these heterogeneous reactions proceed at the liquid/vapor interface by an SN2 mechanism where the nucleophile is chloride ion formed from the ionization of HCl on the aqueous surface. The film of water enhances the otherwise very slow gas phase reaction to occur by (1) stabilizing and localizing the adsorbed N2O5 or NO2 dimer so it is physically accessible for reaction, (2) ionizing the impinging HCl, and (3) activating the adsorbed oxide for nucleophilic attack by chloride. Though both nitrogen oxychloride products are produced by SN2 reactions, the N2O5 mechanism is unusual in that the electrophilic N atom to be attacked oscillates between the two normally equivalent NO2 groups. Chloride ion is found to react with N2O5 less efficiently than with N2O4. The simulations provide an explanation for this. These substitution/elimination mechanisms are new for NOx/y chemistry on thin water films and cannot be derived from small cluster models. PMID- 26140682 TI - Coarse-grained modeling of vesicle responses to active rotational nanoparticles. AB - In recent years, magnetically-driven-rotating superparamagnetic nanoparticles have been emerging as a valuable component in designing targeted drug delivery carriers and cellular killers via membranes' physical rupture. The lack of an in depth understanding of how to control the interaction of rotational nanoparticles (RNPs) with vesicles has hindered progress in the development of their relevant biomedical applications. Here we perform dissipative particle dynamics simulations to analyze the rotation frequencies, size, and coating patterns of the RNPs as they interact with the vesicle so as to provide novel designs of drug delivery applications. Results have revealed that the RNPs are capable of triggering local disturbance around the vesicle and therefore promoting the vesicle translocation toward the RNPs. By investigating the translocation time and driving forces required for RNPs to enter inside the vesicle at various rotation frequencies as well as the interaction energy between coated RNPs and the vesicle, we have tuned the coating pattern of the ligands on the surface of RNPs to open a specified channel in the vesicle for promoting drug delivery. Our findings can provide useful guidelines for the molecular design of patterned RNPs for controllable bio/inorganic interfaces and help establish qualitative rules for the organization and optimization of ligands on the surface of the desired drug delivery carriers. PMID- 26140683 TI - Spontaneous preparation of hierarchically porous silica monoliths with uniform spherical mesopores confined in a well-defined macroporous framework. AB - Hierarchically porous silica monoliths with well-defined interconnected macropores and uniform spherical mesopores were spontaneously prepared by combining polymerization-induced phase separation with an epoxide-mediated sol gel route without any complicated aging and drying and high-temperature heat treatment. The precise control of pore structures can be realized by using propylene oxide (PO) as the gelation mediation agent, poly(ethylene oxide)-block poly(propylene oxide)-block-poly(ethylene oxide) (P123) as the phase-separation inducer as well as the structure-directing agent and 1,3,5-trimethylbenzene (TMB) as the micelle-swelling agent. The as-prepared silica monolith possesses an interesting hierarchically porous structure constructed by 10 nm uniform spherical mesopores confined in a macroporous framework of well-defined 1 MUm macropores, and exhibits a BET surface area as high as 848 m(2) g(-1). Heat treatment at 400-800 degrees C gradually decreases the BET surface area to 195 m(2) g(-1), while most of the uniform mesoporous structure remains intact. PMID- 26140684 TI - Infective endocarditis of the aortic valve in a patient with a coronary artery fistula. PMID- 26140687 TI - Heart Rate Variability: a Follow-up in Elite Soccer Players Throughout the Season. AB - Heart rate variability (HRV) can provide useful information on physiological adaptations to training, but its role is unknown in professional soccer. The aim of this study was to determine an HRV profile in professional soccer over a season. A total of 504 records were made of the heart beat signal throughout a season from 22 professional soccer players. HRV was recorded in a sitting position, early morning and fasting for a period of 10 min. Standard deviation 1 and 2 (SD1, SD2), standard deviation of normal to normal R-R intervals (SDNN), Root Mean Square of the Successive Differences (rMSSD), percentage of RR intervals > 50 ms (pNN50), Sample Entropy (SampEn), Stress Score (SS) and sympathetic/parasympathetic ratio (S/PS ratio) were calculated. SDNN, rMSSD, pNN50, SD1 and SD2 showed an identical behaviour throughout the season, with lower values in the pre-season and the end of the season. SS and S/PS ratio indicated a sympathetic stress alert in the same periods. A weekly recording of the HRV over a 10 min period that includes a Poincare plot with SS and S/PS ratio and at least one variable of the time domain is a useful tool for the follow-up of the individual assimilation of weekly workloads, including the game. PMID- 26140685 TI - Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain. AB - The maternal and paternal genomes play different roles in mammalian brains as a result of genomic imprinting, an epigenetic regulation leading to differential expression of the parental alleles of some genes. Here we investigate genomic imprinting in the cerebellum using a newly developed Bayesian statistical model that provides unprecedented transcript-level resolution. We uncover 160 imprinted transcripts, including 41 novel and independently validated imprinted genes. Strikingly, many genes exhibit parentally biased--rather than monoallelic- expression, with different magnitudes according to age, organ, and brain region. Developmental changes in parental bias and overall gene expression are strongly correlated, suggesting combined roles in regulating gene dosage. Finally, brain specific deletion of the paternal, but not maternal, allele of the paternally biased Bcl-x, (Bcl2l1) results in loss of specific neuron types, supporting the functional significance of parental biases. These findings reveal the remarkable complexity of genomic imprinting, with important implications for understanding the normal and diseased brain. PMID- 26140688 TI - Oxygen Delivery and Muscle Deoxygenation during Continuous, Long- and Short Interval Exercise. AB - This study compared the O2 delivery (a central determinant of VO2) and muscle deoxygenation (reflecting a peripheral determinant of VO2) during intense continuous, long-interval, and short-interval exercise protocols. Twelve young men completed the 3 protocols with equal overall effort. Simultaneous and continuous recordings of central hemodynamics, muscle oxygenation/deoxygenation and VO2 were performed. Peak responses for stroke volume and peripheral resistance did not differ among protocols, whereas peak cardiac output and VO2 were higher in long-interval vs. continuous and short-interval protocols with inactive rest phases (p<0.05). The average responses for all central parameters were higher in continuous and long-interval vs. short-interval exercise (p<0.05); average VO2 and exercise-time above 80% VO2max were also higher in continuous and long-interval vs. short-interval protocol (p<0.05). Muscle de-oxygenation (?Deltadeoxyhemoglobin,?Deltaoxyhemoglobin, ?muscle O2-saturation), as well as the mismatch of O2 delivery and utilization (Deltadeoxyhemoglobin/VO2) were remarkably alike among protocols. In conclusion, all 3 protocols resulted in a great activation of central and peripheral determinants of VO2. When performed with equal overall effort, the intense continuous and interval modalities reveal similarities in muscle O2-utilization response, but differences in central hemodynamic and VO2 responses. Intense continuous and long-interval protocols exert a more commanding role on the cardiovascular system and VO2 response compared to short-interval exercise with inactive rest phases. PMID- 26140686 TI - Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function. AB - Dendritic and axonal arbors of many neuronal types exhibit self-avoidance, in which branches repel each other. In some cases, these neurites interact with those of neighboring neurons, a phenomenon called self/non-self discrimination. The functional roles of these processes remain unknown. In this study, we used retinal starburst amacrine cells (SACs), critical components of a direction selective circuit, to address this issue. In SACs, both processes are mediated by the gamma-protocadherins (Pcdhgs), a family of 22 recognition molecules. We manipulated Pcdhg expression in SACs and recorded from them and their targets, direction-selective ganglion cells (DSGCs). SACs form autapses when self avoidance is disrupted and fail to form connections with other SACs when self/non self discrimination is perturbed. Pcdhgs are also required to prune connections between closely spaced SACs. These alterations degrade the direction selectivity of DSGCs. Thus, self-avoidance, self/non-self discrimination, and synapse elimination are essential for proper function of a circuit that computes directional motion. PMID- 26140689 TI - Autonomic Function Predicts Fitness Response to Short-Term High-Intensity Interval Training. AB - We tested the hypothesis that baseline cardiac autonomic function and its acute response to all-out interval exercise explains individual fitness responses to high-intensity interval training (HIT). Healthy middle-aged sedentary men performed HIT (n=12, 4-6*30 s of all-out cycling efforts with 4-min recovery) or aerobic training (AET, n=9, 40-60 min at 60% of peak workload in exercise test [Loadpeak]), comprising 6 sessions within 2 weeks. Low (LF) and high frequency (HF) power of R-R interval oscillation were analyzed from data recorded at supine and standing position (5+5 min) every morning during the intervention. A significant training effect (p< 0.001), without a training*group interaction, was observed in Loadpeak and peak oxygen consumption (VO2peak). Pre-training supine LF/HF ratio, an estimate of sympathovagal balance, correlated with training outcome in Loadpeak (Spearman's rho [rs]=-0.74, p=0.006) and VO2peak (rs=- 0.59, p=0.042) in the HIT but not the AET group. Also, the mean change in the standing LF/HF ratio in the morning after an acute HIT exercise during the 1(st) week of intervention correlated with training response in Loadpeak (rs=- 0.68, p=0.014) and VO2peak (rs=-0.60, p=0.039) with HIT but not with AET. In conclusion, pre training cardiac sympathovagal balance and its initial alterations in response to acute HIT exercise were related to fitness responses to short-term HIT. PMID- 26140690 TI - Neuromuscular Fatigue after Submaximal Intermittent Contractions in Motorcycle Riders. AB - Highly repetitive submaximal intermittent contractions of the forearm muscles during periods of 30-50 min partially explain why motorcycle races are so demanding for the neuromuscular system. This study investigated the contribution of central and peripheral mechanisms of fatigue on the exerted and contralateral extensor digitorum communis following an intermittent fatigue protocol (IFP) designed for motorcycle riders. 12 riders performed an IFP, which simulates the braking and throttle handle gesture. We examined the time course of recovery of maximal voluntary contraction (MVC), M-wave, motor evoked potential (MEP) to transcranial magnetic stimuli in relaxed and facilitated condition, and the cortical silent period (CSP) at time windows of 1, 3, 5, 10 and 20 min after the IFP. Whereas MVC, M-wave and MEP decreased, CSP lengthened significantly in the fatigued limb after completion of the IFP. Nevertheless, no differences were observed in the contralateral limb. All neurophysiological parameters reverted to baseline values in less than 20 min, while MVC remained lower in the exercised limb. No cross-over effects were observed in the contralateral non-exercised limb. Our results suggest that local factors are those mainly responsible for the incomplete MVC recovery after an intermittent muscle contraction protocol. PMID- 26140691 TI - Physical Demands of Women's Rugby Sevens Matches: Female Athletes in Motion (FAiM) Study. AB - This cross-sectional study characterized the locomotor, heart rate and metabolic power characteristics of women's rugby sevens matches. 4 Canadian teams were monitored during the USA Rugby Sevens event using global positioning system technology with players classified as International (n=16) or Developmental (n=13). Dependent variables were compared between these 2 groups using an ANOVA with duration played as a covariate. International players covered greater distances (1 468+/-88 m) than Developmental (1 252+/-135 m); mostly from more high-intensity (224+/-55 m vs. 131+/-44 m) and sprint distances (128+/-67 m vs. 57+/-44 m). International players also had more distance in high (264+/-36 m vs. 210+/-54 m), elevated (118+/-17 m vs. 76+/-20 m) and maximal (69+/-17 m vs. 30 +/ 15 m) metabolic power categories. Time in various heart rate zones was similar between standards; however peak (187+/-6 bpm vs. 194+/-5 bpm) and mean (172+/-7 bpm vs. 180+/-9 bpm) heart rate values were lower for International players. International players had greater fitness scores (YoYo IRT1-1 160+/-191 m vs. 781+/-129 m) and maximal sprint speed (27.3+/-0.7 vs. 26.0+/-1.5 km.h(-1)). The current findings highlight developmental gaps in match demands between standards and show that field-based fitness tests discriminate among levels of play. The external and internal loads should be used by sport organizations to assist in forming appropriate training plans and utilize the performance tests to help monitor player development. PMID- 26140692 TI - Structure, Processes, and Retrospective Outcomes From an Intensive Comprehensive Aphasia Program. AB - PURPOSE: This study describes the structure, processes, and outcomes of an intensive comprehensive aphasia program (ICAP). The aim was to identify treatment gains and determine if outcomes were significantly different between participants grouped according to severity and type of aphasia, and time postonset. METHOD: Data from 74 first-time ICAP participants were analyzed. Pre- and posttreatment scores on the Western Aphasia Battery-Revised and other impairment and participation measures were compared using paired t tests. Analyses of variance were used to compare outcomes related to aphasia severity (severe, moderate, and mild aphasia), aphasia type (fluent, nonfluent), and chronicity (0-6 months postonset, 7-12 months postonset, and 12+ months postonset). RESULTS: Participants made significant changes on all impairment and participation measures. Large effect sizes were noted for one participation and three impairment measures. Medium effect sizes were noted for one impairment and three participation measures. There was no significant difference among groups on any factor. CONCLUSION: ICAPs can have a significant effect on the language impairment and participation of people with aphasia, but further research is required to determine if the effect is comparable to other types of service delivery. PMID- 26140693 TI - IRAK-M regulates the inhibition of TLR-mediated macrophage immune response during late in vitro Leishmania donovani infection. AB - Intramacrophage protozoan parasite Leishmania donovani, causative agent of visceral leishmaniasis, escapes Toll-like receptor (TLR) dependent early host immune response by inducing the deubiquitinating enzyme A20, which is sustained up to 6 h postinfection only. Therefore, Leishmania must apply other means to deactivate late host responses. Here, we elucidated the role of IL-1 receptor associated kinase M (IRAK-M), a negative regulator of TLR signaling, in downregulating macrophage proinflammatory response during late hours of in vitro infection. Our data reveal a sharp decline in IRAK1 and IRAK4 phosphorylation at 24 h postinfection along with markedly reduced association of IRAK1-TNF receptor associated factor 6, which is mandatory for TLR activation. In contrast, IRAK-M was induced after A20 levels decreased and reached a maximum at 24 h postinfection. IRAK-M induction coincided with increased stimulation of TGF-beta, a hallmark cytokine of visceral infection. TGF-beta-dependent signaling-mediated induction of SMAD family of proteins, 2, 3, and 4 plays important roles in transcriptional upregulation of IRAK-M. In infected macrophages, siRNA-mediated silencing of IRAK-M displayed enhanced IRAK1 and IRAK4 phosphorylation with a concomitant increase in downstream NF-kappaB activity and reduced parasite survival. Taken together, the results suggest that IRAK-M may be targeted by L. donovani to inhibit TLR-mediated proinflammatory response late during in vitro infection. PMID- 26140694 TI - Ocular Chlamydia Trachoma. PMID- 26140695 TI - Predicting outcomes following CRT: the quest continues. PMID- 26140696 TI - Multimodal MRI can identify perfusion and metabolic changes in the invasive margin of glioblastomas. AB - PURPOSE: To use perfusion and magnetic resonance (MR) spectroscopy to compare the diffusion tensor imaging (DTI)-defined invasive and noninvasive regions. Invasion of normal brain is a cardinal feature of glioblastomas (GBM) and a major cause of treatment failure. DTI can identify invasive regions. MATERIALS AND METHODS: In all, 50 GBM patients were imaged preoperatively at 3T with anatomic sequences, DTI, dynamic susceptibility perfusion MR (DSCI), and multivoxel spectroscopy. The DTI and DSCI data were coregistered to the spectroscopy data and regions of interest (ROIs) were made in the invasive (determined by DTI), noninvasive regions, and normal brain. Values of relative cerebral blood volume (rCBV), N acetyl aspartate (NAA), myoinositol (mI), total choline (Cho), and glutamate + glutamine (Glx) normalized to creatine (Cr) and Cho/NAA were measured at each ROI. RESULTS: Invasive regions showed significant increases in rCBV, suggesting angiogenesis (invasive rCBV 1.64 [95% confidence interval, CI: 1.5-1.76] vs. noninvasive 1.14 [1.09-1.18]; P < 0.001), Cho/Cr (invasive 0.42 [0.38-0.46] vs. noninvasive 0.35 [0.31-0.38]; P = 0.02) and Cho/NAA (invasive 0.54 [0.41-0.68] vs. noninvasive 0.37 [0.29-0.45]; P = < 0.03), suggesting proliferation, and Glx/Cr (invasive 1.54 [1.27-1.82] vs. noninvasive 1.3 [1.13-1.47]; P = 0.028), suggesting glutamate release; and a significantly reduced NAA/Cr (invasive 0.95 [0.85-1.05] vs. noninvasive 1.19 [1.06-1.31]; P = 0.008). The mI/Cr was not different between the three ROIs (invasive 1.2 [0.99-1.41] vs. noninvasive 1.3 [1.14-1.46]; P = 0.68). In the noninvasive regions, the values were not different from normal brain. CONCLUSION: Combining DTI to identify the invasive region with perfusion and spectroscopy, we can identify changes in invasive regions not seen in noninvasive regions. PMID- 26140697 TI - Longitudinal evolution of incidentally detected solitary pure ground-glass nodules on CT: relation to clinical metrics. AB - PURPOSE: We aimed to assess the relation between basic clinical parameters and evolution of solitary pure ground-glass nodules (pGGN) in the lungs. METHODS: Baseline and follow-up computed tomography (CT) of patients with solitary pGGN were selected and two radiologists independently reviewed CTs for nodule characterization. CT features of solitary pGGN were manually measured maximum diameter (D1) and its orthogonal diameter (D2), mean diameter (mD), D1 to D2 ratio as surrogate of roundness, and location according to lobar anatomy. Longitudinal changes were assessed and solitary pGGNs were classified as resolved or persisting. Persisting nodules were further classified as stable or grown according to an increase in mD of >=2 mm or appearance of solid component. Baseline CT features of solitary pGGNs and clinical metrics of patients were compared between resolved and persisting nodules and, thereafter, between stable and grown lesions. RESULTS: A total of 95 subjects with solitary pGGN were included. After a median 16-month follow-up, 20 nodules resolved, while 75 persisted. Among persisting nodules, 18 were grown and 57 were stable. Grown nodules showed larger D1 and mD compared with stable pGGNs (P < 0.001). Subjects with grown nodules were older (P = 0.021). Logistic regression analyses showed higher likelihood of growth for nodules >=10 mm (odds ratio [OR], 8.355; P = 0.001) and subjects older than 67 years (OR, 3.656; P = 0.034). CONCLUSION: Nodules >=10 mm in subjects older than 67 years showed higher likelihood of growth. These data could contribute to a more individual approach to the management of solitary pGGN. PMID- 26140698 TI - Glycoprotein nonmetastatic melanoma protein B ameliorates skeletal muscle lesions in a SOD1G93A mouse model of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons and subsequent muscular atrophy. The quality of life of patients with ALS is significantly improved by ameliorating muscular symptoms. We previously reported that glycoprotein nonmetastatic melanoma protein B (GPNMB; osteoactivin) might serve as a target for ALS therapy. In the present study, superoxide dismutase 1/glycine residue 93 changed to alanine (SOD1(G93A) ) transgenic mice were used as a model of ALS. Expression of the C-terminal fragment of GPNMB was increased in the skeletal muscles of SOD1(G93A) mice and patients with sporadic ALS. SOD1(G93A) /GPNMB transgenic mice were generated to determine whether GPNMB expression ameliorates muscular symptoms. The weight and cross-sectional area of the gastrocnemius muscle, number and cross-sectional area of myofibers, and denervation of neuromuscular junctions were ameliorated in SOD1(G93A) /GPNMB vs. SOD1(G93A) mice. Furthermore, direct injection of a GPNMB expression plasmid into the gastrocnemius muscle of SOD1(G93A) mice increased the numbers of myofibers and prevented myofiber atrophy. These findings suggest that GPNMB directly affects skeletal muscle and prevents muscular pathology in SOD1(G93A) mice and may therefore serve as a target for therapy of ALS. PMID- 26140699 TI - Volumetric MRI of the lungs during forced expiration. AB - PURPOSE: Lung function is typically characterized by spirometer measurements, which do not offer spatially specific information. Imaging during exhalation provides spatial information but is challenging due to large movement over a short time. The purpose of this work is to provide a solution to lung imaging during forced expiration using accelerated magnetic resonance imaging. The method uses radial golden angle stack-of-stars gradient echo acquisition and compressed sensing reconstruction. METHODS: A technique for dynamic three-dimensional imaging of the lungs from highly undersampled data is developed and tested on six subjects. This method takes advantage of image sparsity, both spatially and temporally, including the use of reference frames called bookends. Sparsity, with respect to total variation, and residual from the bookends, enables reconstruction from an extremely limited amount of data. RESULTS: Dynamic three dimensional images can be captured at sub-150 ms temporal resolution, using only three (or less) acquired radial lines per slice per timepoint. The images have a spatial resolution of 4.6*4.6*10 mm. Lung volume calculations based on image segmentation are compared to those from simultaneously acquired spirometer measurements. CONCLUSION: Dynamic lung imaging during forced expiration is made possible by compressed sensing accelerated dynamic three-dimensional radial magnetic resonance imaging. Magn Reson Med 75:2295-2302, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26140701 TI - A New Perspective on Li-SO2 Batteries for Rechargeable Systems. AB - Primary Li-SO2 batteries offer a high energy density in a wide operating temperature range with exceptionally long shelf life and have thus been frequently used in military and aerospace applications. Although these batteries have never been demonstrated as a rechargeable system, herein, we show that the reversible formation of Li2S2O4, the major discharge product of Li-SO2 battery, is possible with a remarkably smaller charging polarization than that of a Li-O2 battery without the use of catalysts. The rechargeable Li-SO2 battery can deliver approximately 5400 mAh g(-1) at 3.1 V, which is slightly higher than the performance of a Li-O2 battery. In addition, the Li-SO2 battery can be operated with the aid of a redox mediator, exhibiting an overall polarization of less than 0.3 V, which results in one of the highest energy efficiencies achieved for Li gas battery systems. PMID- 26140700 TI - Preconcentration of indapamide from human urine using molecularly imprinted solid phase extraction. AB - A simple, sensitive, and selective molecularly imprinted solid-phase extraction and spectrophotometric method has been developed for the clean-up and preconcentration of indapamide from human urine. Molecularly imprinted polymers were prepared by a non-covalent imprinting approach using indapamide as a template molecule, 2-(trifluoromethyl) acrylic acid as a functional monomer, ethylene glycol dimethacrylate as a crosslinker, N,N-azobisisobutyronitrile as a thermal initiator and acetonitrile as a porogenic solvent. A non-imprinted polymer was also prepared in the same way, but in the absence of template. Molecularly imprinted polymer and non-imprinted polymer sorbents were dry-packed into solid-phase extraction cartridges. Eluates from cartridges were analyzed using a spectrophotometer for the determination of indapamide by referring to the calibration curve in the range 0.14-1.50 MUg/mL. Preconcentration factor, limit of detection, and limit of quantification were 16.30, 0.025 MUg/mL, and 0.075 MUg/mL, respectively. A relatively high imprinting factor (9.3) was also achieved and recovery values for the indapamide spiked into human urine were in the range of 80.1-81.2%. In addition, relatively low within-day (0.17-0.42%) and between day (1.1-1.4%) precision values were obtained as well. The proposed molecularly imprinted solid-phase extraction and spectrophotometric method was successfully applied to selective extraction, preconcentration, and determination of indapamide from human urine samples. PMID- 26140702 TI - Constrained numerical gradients and composite gradients: Practical tools for geometry optimization and potential energy surface navigation. AB - A method is proposed to easily reduce the number of energy evaluations required to compute numerical gradients when constraints are imposed on the system, especially in connection with rigid fragment optimization. The method is based on the separation of the coordinate space into a constrained and an unconstrained space, and the numerical differentiation is done exclusively in the unconstrained space. The decrease in the number of energy calculations can be very important if the system is significantly constrained. The performance of the method is tested on systems that can be considered as composed of several rigid groups or molecules, and the results show that the error with respect to conventional optimizations is of the order of the convergence criteria. Comparison with another method designed for rigid fragment optimization proves the present method to be competitive. The proposed method can also be applied to combine numerical and analytical gradients computed at different theory levels, allowing an unconstrained optimization with numerical differentiation restricted to the most significant degrees of freedom. This approach can be a practical alternative when analytical gradients are not available at the desired computational level and full numerical differentiation is not affordable. PMID- 26140703 TI - Concise Total Synthesis of Ivorenolide B. AB - An expeditious route to the potential immunosuppressive lead compound ivorenolide B (1) is described, which relies on the formation of the distinctive 1,3-diyne subunit embedded into the 17-membered framework of this target by ring-closing alkyne metathesis (RCAM). This key transformation was accomplished with the aid of the molybdenum alkylidyne complex 7, which turned out to be compatible with the acid sensitive propargylic alcohol substituents as well as the terminal alkyne unit present in the cyclization precursor. As the presence of such functionality had been detrimental for alkyne metathesis until very recently, this example illustrates the excellent application profile of this new catalyst as well as the rapidly increasing scope of the transformation. Its structural outreach can be further increased by subjecting cyclo-1,3-diynes to appropriate post-metathetic transformations, most notably with the help of alkynophilic gold or palladium catalysts. This aspect is illustrated by the conversion of the model compound 4 into various cyclophane products. PMID- 26140704 TI - Interpreted Recognition Process: A Highly Sensitive and Selective Luminescence Chemosensor. AB - A luminescence-sensing process based on coordination compound [H2 N(CH3 )2 ]3 [Tb(dipic)3 ] was developed. It shows fast response (within 1 min), high selectivity, and is ultrasensitive to detect Fe(3+) or Cr(3+) in aqueous solution and living cells (KSV values are calculated to be 3.6*10(4) L mol(-1) for Fe(3+) and 1.9*10(4) L mol(-1) for Cr(3+) ). The whole recognition process has been witnessed through electrospray ionization mass spectrometry (ESI-MS) analysis, and the ligand-transfer-induced luminescence-quenching mechanism is interpreted. This work contributes to extend the potential applications of lanthanide coordination compounds (LnCCs) in the fields of biological and environmental technologies. PMID- 26140705 TI - Construction and Self-Assembly of Single-Chain Polymer Nanoparticles via Coordination Association and Electrostatic Repulsion in Water. AB - Simultaneous coordination-association and electrostatic-repulsion interactions play critical roles in the construction and stabilization of enzymatic function metal centers in water media. These interactions are promising for construction and self-assembly of artificial aqueous polymer single-chain nanoparticles (SCNPs). Herein, the construction and self-assembly of dative-bonded aqueous SCNPs are reported via simultaneous coordination-association and electrostatic repulsion interactions within single chains of histamine-based hydrophilic block copolymer. The electrostatic-repulsion interactions are tunable through adjusting the imidazolium/imidazole ratio in response to pH, and in situ Cu(II) coordination leads to the intramolecular association and single-chain collapse in acidic water. SCNPs are stabilized by the electrostatic repulsion of dative bonded block and steric shielding of nonionic water-soluble block, and have a huge specific surface area of function metal centers accessible to substrates in acidic water. Moreover, SCNPs can assemble into micelles, networks, and large particles programmably in response to the solution pH. These unique media sensitive phase-transformation behaviors provide a general, facile, and versatile platform for the fabrication of enzyme-inspired smart aqueous catalysts. PMID- 26140706 TI - Curved Oligophenylenes as Donors in Shape-Persistent Donor-Acceptor Macrocycles with Solvatofluorochromic Properties. AB - Many optoelectronic organic materials are based on donor-acceptor (D-A) systems with heteroatom-containing electron donors. Herein, we introduce a new molecular design for all-carbon curved oligoparaphenylenes as donors, which results in the generation of unique shape-persistent D-A macrocycles. Two types of acceptor inserted cycloparaphenylenes were synthesized. These macrocycles display positive solvatofluorochromic properties owing to their D-A characteristics, which were confirmed by theoretical and electrochemical studies. PMID- 26140707 TI - Carbon-Based Materials for Lithium-Ion Batteries, Electrochemical Capacitors, and Their Hybrid Devices. AB - A rapidly developing market for portable electronic devices and hybrid electrical vehicles requires an urgent supply of mature energy-storage systems. As a result, lithium-ion batteries and electrochemical capacitors have lately attracted broad attention. Nevertheless, it is well known that both devices have their own drawbacks. With the fast development of nanoscience and nanotechnology, various structures and materials have been proposed to overcome the deficiencies of both devices to improve their electrochemical performance further. In this Review, electrochemical storage mechanisms based on carbon materials for both lithium-ion batteries and electrochemical capacitors are introduced. Non-faradic processes (electric double-layer capacitance) and faradic reactions (pseudocapacitance and intercalation) are generally explained. Electrochemical performance based on different types of electrolytes is briefly reviewed. Furthermore, impedance behavior based on Nyquist plots is discussed. We demonstrate the influence of cell conductivity, electrode/electrolyte interface, and ion diffusion on impedance performance. We illustrate that relaxation time, which is closely related to ion diffusion, can be extracted from Nyquist plots and compared between lithium-ion batteries and electrochemical capacitors. Finally, recent progress in the design of anodes for lithium-ion batteries, electrochemical capacitors, and their hybrid devices based on carbonaceous materials are reviewed. Challenges and future perspectives are further discussed. PMID- 26140708 TI - Satellite Cells and Skeletal Muscle Regeneration. AB - Skeletal muscles are essential for vital functions such as movement, postural support, breathing, and thermogenesis. Muscle tissue is largely composed of long, postmitotic multinucleated fibers. The life-long maintenance of muscle tissue is mediated by satellite cells, lying in close proximity to the muscle fibers. Muscle satellite cells are a heterogeneous population with a small subset of muscle stem cells, termed satellite stem cells. Under homeostatic conditions all satellite cells are poised for activation by stimuli such as physical trauma or growth signals. After activation, satellite stem cells undergo symmetric divisions to expand their number or asymmetric divisions to give rise to cohorts of committed satellite cells and thus progenitors. Myogenic progenitors proliferate, and eventually differentiate through fusion with each other or to damaged fibers to reconstitute fiber integrity and function. In the recent years, research has begun to unravel the intrinsic and extrinsic mechanisms controlling satellite cell behavior. Nonetheless, an understanding of the complex cellular and molecular interactions of satellite cells with their dynamic microenvironment remains a major challenge, especially in pathological conditions. The goal of this review is to comprehensively summarize the current knowledge on satellite cell characteristics, functions, and behavior in muscle regeneration and in pathological conditions. PMID- 26140709 TI - Potential Central Nervous System Involvement in Sudden Unexpected Infant Deaths and the Sudden Infant Death Syndrome. AB - Sudden unexpected infant death (SUID) in infancy which includes Sudden Infant Death Syndrome (SIDS) is the commonest diagnosed cause of death in the United States for infants 1 month to 1 year of age. Central nervous system mechanisms likely contribute to many of these deaths. We discuss some of these including seizure disorders, prolonged breath holding, arousal from sleep and its habituation, laryngeal reflex apnea potentiated by upper airway infection, and failure of brainstem-mediated autoresuscitation. In the conclusions section, we speculate how lives saved through back sleeping might result in later developmental problems in certain infants who otherwise might have died while sleeping prone. PMID- 26140710 TI - Cardiac Physiology of Aging: Extracellular Considerations. AB - Aging is a major risk factor for the development of cardiovascular disease, with the majority of affected patients being elderly. Progressive changes to myocardial structure and function occur with aging, often in concert with underlying pathologies. However, whether chronological aging results in a remodeled "aged substrate" has yet to be established. In addition to myocyte contractility, myocardial performance relies heavily on the cardiac extracellular matrix (ECM), the roles of which are as dynamic as they are significant; including providing structural integrity, assisting in force transmission throughout the cardiac cycle and acting as a signaling medium for communication between cells and the extracellular environment. In the healthy heart, ECM homeostasis must be maintained, and matrix deposition is in balance with degradation. Consequently, alterations to, or misregulation of the cardiac ECM has been shown to occur in both aging and in pathological remodeling with disease. Mounting evidence suggests that age-induced matrix remodeling may occur at the level of ECM control; including collagen synthesis, deposition, maturation, and degradation. Furthermore, experimental studies using aged animal models not only suggest that the aged heart may respond differently to insult than the young, but the identification of key players specific to remodeling with age may hold future therapeutic potential for the treatment of cardiac dysfunction in the elderly. This review will focus on the role of the cardiac interstitium in the physiology of the aging myocardium, with particular emphasis on the implications to age-related remodeling in disease. PMID- 26140711 TI - Treatment of Myocardial Ischemia/Reperfusion Injury by Ischemic and Pharmacological Postconditioning. AB - Timely reperfusion is the only way to salvage ischemic myocardium from impending infarction. However, reperfusion also adds a further component to myocardial injury such that the ultimate infarct size is the result of both ischemia- and reperfusion-induced injury. Modification of reperfusion can attenuate reperfusion injury and thus reduce infarct size. Ischemic postconditioning is a maneuver of repeated brief interruption of reperfusion by short-lasting coronary occlusions which results in reduced infarct size. Cardioprotection by ischemic postconditioning is mediated through delayed reversal of acidosis and the activation of a complex signal transduction cascade, including triggers such as adenosine, bradykinin, and opioids, mediators such as protein kinases and, notably, mitochondrial function as effector. Inhibition of the mitochondrial permeability transition pore appears to be a final signaling step of ischemic postconditioning. Several drugs which recruit in part such signaling steps of ischemic postconditioning can induce cardioprotection, even when the drug is only administered at reperfusion, that is, there is also pharmacological postconditioning. Ischemic and pharmacological postconditioning have been translated to patients with acute myocardial infarction in proof-of-concept studies, but further mechanistic insight is needed to optimize the conditions and algorithms of cardioprotection by postconditioning. PMID- 26140713 TI - Hypothalamic-Pituitary--Adrenal Axis-Feedback Control. AB - The hypothalamo-pituitary-adrenal axis (HPA) is responsible for stimulation of adrenal corticosteroids in response to stress. Negative feedback control by corticosteroids limits pituitary secretion of corticotropin, ACTH, and hypothalamic secretion of corticotropin-releasing hormone, CRH, and vasopressin, AVP, resulting in regulation of both basal and stress-induced ACTH secretion. The negative feedback effect of corticosteroids occurs by action of corticosteroids at mineralocorticoid receptors (MR) and/or glucocorticoid receptors (GRs) located in multiple sites in the brain and in the pituitary. The mechanisms of negative feedback vary according to the receptor type and location within the brain hypothalmo-pituitary axis. A very rapid nongenomic action has been demonstrated for GR action on CRH neurons in the hypothalamus, and somewhat slower nongenomic effects are observed in the pituitary or other brain sites mediated by GR and/or MR. Corticosteroids also have genomic actions, including repression of the pro opiomelanocortin (POMC) gene in the pituitary and CRH and AVP genes in the hypothalamus. The rapid effect inhibits stimulated secretion, but requires a rapidly rising corticosteroid concentration. The more delayed inhibitory effect on stimulated secretion is dependent on the intensity of the stimulus and the magnitude of the corticosteroid feedback signal, but also the neuroanatomical pathways responsible for activating the HPA. The pathways for activation of some stressors may partially bypass hypothalamic feedback sites at the CRH neuron, whereas others may not involve forebrain sites; therefore, some physiological stressors may override or bypass negative feedback, and other psychological stressors may facilitate responses to subsequent stress. PMID- 26140714 TI - Wnt Signaling in Cardiac Disease. AB - Wnt signaling encompasses multiple and complex signaling cascades and is involved in many developmental processes such as tissue patterning, cell fate specification, and control of cell division. Consequently, accurate regulation of signaling activities is essential for proper embryonic development. Wnt signaling is mostly silent in the healthy adult organs but a reactivation of Wnt signaling is generally observed under pathological conditions. This has generated increasing interest in this pathway from a therapeutic point of view. In this review article, the involvement of Wnt signaling in cardiovascular development will be outlined, followed by its implication in myocardial infarct healing, cardiac hypertrophy, heart failure, arrhythmias, and atherosclerosis. The initial experiments not always offer consensus on the effects of activation or inactivation of the pathway, which may be attributed to (i) the type of cardiac disease, (ii) timing of the intervention, and (iii) type of cells that are targeted. Therefore, more research is needed to determine the exact implication of Wnt signaling in the conditions mentioned above to exploit it as a powerful therapeutic target. PMID- 26140712 TI - Role of Microvascular Disruption in Brain Damage from Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood-brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug-treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis. PMID- 26140717 TI - Effects of Stroke on the Autonomic Nervous System. AB - Stroke is the fourth leading cause of death in the United States and the second most common cause of death worldwide; stroke is also the leading cause of long term disability worldwide. It is clear that the consequences of cerebral ischemia reach beyond the brain into the periphery, and a significant number of stroke related deaths are the result of conditions that develop poststroke in the periphery. The two leading causes of non-neurogenic death poststroke are cardiac abnormalities and infections. Changes in autonomic nervous system function that favor increased sympathetic nervous system activity and reduced parasympathetic nervous system activity appear to be causative factors in both conditions. Here, we review the evidence that sympathetic nervous system activity increases and parasympathetic nervous system activity declines poststroke. We discuss effects of autonomic dysfunction on cardiac arrhythmias and heart rate variability. Finally, we discuss the evidence supporting a role for autonomic dysfunction in the increased incidence of infection poststroke. Although the death rate from stroke is declining in the United States, the incidence of stroke is not. With more patients surviving the initial ischemic event it is important that we broaden our understanding of the chronic effects of stroke on the human condition. PMID- 26140715 TI - Estradiol Membrane-Initiated Signaling and Female Reproduction. AB - The discoveries of rapid, membrane-initiated steroid actions and central nervous system steroidogenesis have changed our understanding of the neuroendocrinology of reproduction. Classical nuclear actions of estradiol and progesterone steroids affecting transcription are essential. However, with the discoveries of membrane associated steroid receptors, it is becoming clear that estradiol and progesterone have neurotransmitter-like actions activating intracellular events. Ultimately, membrane-initiated actions can influence transcription. Estradiol membrane-initiated signaling (EMS) modulates female sexual receptivity and estrogen feedback regulating the luteinizing hormone (LH) surge. In the arcuate nucleus, EMS activates a lordosis-regulating circuit that extends to the medial preoptic nucleus and subsequently to the ventromedial nucleus (VMH)--the output from the limbic and hypothalamic regions. Here, we discuss how EMS leads to an active inhibition of lordosis behavior. To stimulate ovulation, EMS facilitates astrocyte synthesis of progesterone (neuroP) in the hypothalamus. Regulation of GnRH release driving the LH surge is dependent on estradiol-sensitive kisspeptin (Kiss1) expression in the rostral periventricular nucleus of the third ventricle (RP3V). NeuroP activation of the LH surge depends on Kiss1, but the specifics of signaling have not been well elucidated. RP3V Kiss1 neurons appear to integrate estradiol and progesterone information which feeds back onto GnRH neurons to stimulate the LH surge. In a second population of Kiss1 neurons, estradiol suppresses the surge but maintains tonic LH release, another critical component of the estrous cycle. Together, evidence suggests that regulation of reproduction involves membrane action of steroids, some of which are synthesized in the brain. PMID- 26140716 TI - The Dystrophin Complex: Structure, Function, and Implications for Therapy. AB - The dystrophin complex stabilizes the plasma membrane of striated muscle cells. Loss of function mutations in the genes encoding dystrophin, or the associated proteins, trigger instability of the plasma membrane, and myofiber loss. Mutations in dystrophin have been extensively cataloged, providing remarkable structure-function correlation between predicted protein structure and clinical outcomes. These data have highlighted dystrophin regions necessary for in vivo function and fueled the design of viral vectors and now, exon skipping approaches for use in dystrophin restoration therapies. However, dystrophin restoration is likely more complex, owing to the role of the dystrophin complex as a broad cytoskeletal integrator. This review will focus on dystrophin restoration, with emphasis on the regions of dystrophin essential for interacting with its associated proteins and discuss the structural implications of these approaches. PMID- 26140719 TI - Endocrine-Autonomic Linkages. AB - Interaction between the autonomic nervous system and the neuroendocrine system is critical for maintenance of homeostasis in a wide variety of physiological parameters such as body temperature, fluid and electrolyte balance, and blood pressure and volume. The anatomical and physiological mechanisms underlying integration of the neuroendocrine and autonomic mechanisms responsible for eliciting integrated autonomic and neuroendocrine actions are the focus of this article. This includes a focus on the hypothalamic paraventricular nucleus, because it includes both neuroendocrine neurons and preganglionic autonomic neurons that regulate sympathetic and parasympathetic outflow. The "wired" and "nonwired" mechanisms within PVN that facilitate communication between these neuronal populations are described. The impact of peripheral hormones, specifically the adrenal and gonadal steroids, on the neuroendocrine and autonomic systems is discussed, and exercise is used as a specific example of a physiological challenge/stress that requires precise integration of neuroendocrine and autonomic responses to maintain cardiovascular, fluid, and energy homeostasis. PMID- 26140720 TI - Cardiac Physiology of Pregnancy. AB - Although the physiology of the heart and vascular system has not changed, there are many things we have learned and are still learning today. Research related to heart adaptations during pregnancy has been performed since the 1930s. Since the mid-1950s, researchers began to look at changes in the maternal cardiovascular system during exercise while pregnant. Research related to exercise during pregnancy and offspring heart development began and has continued since the 1970s. We will review the normal female cardiovascular system adaptations to pregnancy in general. Additionally, topics related to maternal cardiac adaptations to pregnancy during acute exercise, as well as the chronic conditioning response from exercise training will be explored. Since physical activity during pregnancy influences fetal development, the fetal cardiac development will be discussed in regards to acute and chronic maternal exercise. Similarly, the influence of various types of maternal exercise on acute and chronic fetal heart responses will be described. Briefly, the topics related to how and if there is maternal-fetal synchrony will be explained. Lastly, the developmental changes of the fetal cardiovascular system that persist after birth will be explored. Overall, the article will discuss maternal cardiac physiology related to changes with normal pregnancy, and exercise during pregnancy, as well as fetal cardiac physiology related to changes with normal development, and exercise during pregnancy as well as developmental changes in offspring after birth. PMID- 26140721 TI - Cerebral Vascular Control and Metabolism in Heat Stress. AB - This review provides an in-depth update on the impact of heat stress on cerebrovascular functioning. The regulation of cerebral temperature, blood flow, and metabolism are discussed. We further provide an overview of vascular permeability, the neurocognitive changes, and the key clinical implications and pathologies known to confound cerebral functioning during hyperthermia. A reduction in cerebral blood flow (CBF), derived primarily from a respiratory induced alkalosis, underscores the cerebrovascular changes to hyperthermia. Arterial pressures may also become compromised because of reduced peripheral resistance secondary to skin vasodilatation. Therefore, when hyperthermia is combined with conditions that increase cardiovascular strain, for example, orthostasis or dehydration, the inability to preserve cerebral perfusion pressure further reduces CBF. A reduced cerebral perfusion pressure is in turn the primary mechanism for impaired tolerance to orthostatic challenges. Any reduction in CBF attenuates the brain's convective heat loss, while the hyperthermic-induced increase in metabolic rate increases the cerebral heat gain. This paradoxical uncoupling of CBF to metabolism increases brain temperature, and potentiates a condition whereby cerebral oxygenation may be compromised. With levels of experimentally viable passive hyperthermia (up to 39.5-40.0 degrees C core temperature), the associated reduction in CBF (~ 30%) and increase in cerebral metabolic demand (~ 10%) is likely compensated by increases in cerebral oxygen extraction. However, severe increases in whole-body and brain temperature may increase blood-brain barrier permeability, potentially leading to cerebral vasogenic edema. The cerebrovascular challenges associated with hyperthermia are of paramount importance for populations with compromised thermoregulatory control -for example, spinal cord injury, elderly, and those with preexisting cardiovascular diseases. PMID- 26140722 TI - Placental Gas Exchange and the Oxygen Supply to the Fetus. AB - The oxygen supply of the fetus depends on the blood oxygen content and flow rate in the uterine and umbilical arteries and the diffusing capacity of the placenta. Oxygen consumption by the placenta is a significant factor and a potential limitation on availability to the fetus. The relevance of these several factors as well as responses to acute or sustained hypoxia has been explored in the sheep model. In addition, much has been learned in the context of hypobaric hypoxia by studying human populations that have resided at high altitude for varying periods of time. Embryonic development occurs under anaerobic conditions and even the fetus is adapted to a low oxygen environment. Nevertheless, there is a reserve capacity, and during acute hypoxia the fetus can counter a 50% reduction in oxygen delivery by increasing fractional extraction. During sustained hypoxia, on the other hand, fetal growth is slowed, although oxygen consumption is unaltered when corrected for fetal mass. Similarly, birth weight is reduced in humans living at high altitude even if the effect is tempered in those with a long highland ancestry. Placental mass changes little during sustained hypoxia in sheep or humans at high altitude. This conceals the fact that there are structural changes and that placental oxygen consumption is reduced. The underlying mechanisms are a current focus of research. One intriguing possibility is that increased anaerobic metabolism of glucose in the placenta spares oxygen for the fetus but reduces its supply of substrate and thereby limits fetal growth. PMID- 26140718 TI - Platelets and Their Interactions with Other Immune Cells. AB - Platelets are anucleate blood cells, long known to be critically involved in hemostasis and thrombosis. In addition to their role in blood clots, increasing evidence reveals significant roles for platelets in inflammation and immunity. However, the notion that platelets represent immune cells is not broadly recognized in the field of Physiology. This article reviews the role of platelets in inflammation and immune responses, and highlights their interactions with other immune cells, including examples of major functional consequences of these interactions. PMID- 26140723 TI - Role of the Thyroid System in Myelination and Neural Connectivity. AB - The role of thyroid hormone on brain development is dramatically illustrated by "cretinism," a severe mental retardation due to iodine deficiency and maternal hypothyroidism during gestation. In the last decades, the molecular bases of the cellular action of thyroid hormone in the nervous tissue have been at least partially elucidated, and the emerged picture is much more complex than expected. In this article, the main mechanisms determining thyroid hormone availability, nuclear and membrane receptor occupancy and downstream action, gene expression, and nongenomic mechanism are reviewed, focusing on myelination and myelin turnover. PMID- 26140725 TI - Neuroendocrine Regulation of Hydromineral Homeostasis. AB - Since the crucial evolutionary change from an aqueous to a terrestrial environment, all living organisms address the primordial task of equilibrating the ingestion/production of water and electrolytes (primarily sodium) with their excretion. In mammals, the final route for the excretion of these elements is mainly through the kidneys, which can eliminate concentrated or diluted urine according to the requirements. Despite their primary role in homeostasis, the kidneys are not able to recover water and solutes lost through other systems. Therefore, the selective stimulation or inhibition of motivational and locomotor behavior becomes essential to initiate the search and acquisition of water and/or sodium from the environment. Indeed, imbalances affecting the osmolality and volume of body fluids are dramatic challenges to the maintenance of hydromineral homeostasis. In addition to behavioral changes, which are integrated in the central nervous system, most of the systemic responses recruited to restore hydroelectrolytic balance are accomplished by coordinated actions of the cardiovascular, autonomic and endocrine systems, which determine the appropriate renal responses. The activation of sequential and redundant mechanisms (involving local and systemic factors) produces accurate and self-limited effector responses. From a physiological point of view, understanding the mechanisms underlying water and sodium balance is intriguing and of great interest for the biomedical sciences. Therefore, the present review will address the biophysical, evolutionary and historical perspectives concerning the integrative neuroendocrine control of hydromineral balance, focusing on the major neural and endocrine systems implicated in the control of water and sodium balance. PMID- 26140726 TI - Anthracycline-Induced Cardiomyopathy in Adults. AB - Anthracyclines are one of the most commonly used antineoplastic agent classes, and a core part of the treatment in breast cancers, hematological malignancies, and sarcomas. Their benefit is decreased by their well-recognized cardiotoxicity. The purpose of this review is to outline the presentation, mechanisms, diagnosis, and treatment of anthracyclines-induced cardiotoxicity. Symptomatic heart failure occurs in 2% to 5% of patients treated with anthrayclines and may be higher in older patients or patients with cardiovascular risk factors. The mechanisms involved in anthracycline-induced cardiotoxicity involve myocyte loss by apoptosis in the presence of a limited regenerative capacity. Once symptomatic, anthracycline-induced cardiotoxicity is associated with markedly decreased survival. Left ventricular ejection fraction (LVEF), mostly determined using echocardiography, is used to monitor patients treated with anthracyclines. As more than 1/3 of patients treated with anthracyclines do not recover their baseline LVEF once it is decreased, more sensitive echocardiographic indices of LV function such as myocardial deformation or biomarkers have been studied in patients monitoring. Cardioprotective treatments such as angiotensin-converting enzyme inhibitors, beta-blockers, iron chelators, statins, and metformin are also the topic of research efforts. PMID- 26140727 TI - The Gastrointestinal Circulation: Physiology and Pathophysiology. AB - The gastrointestinal (GI) circulation receives a large fraction of cardiac output and this increases following ingestion of a meal. While blood flow regulation is not the intense phenomenon noted in other vascular beds, the combined responses of blood flow, and capillary oxygen exchange help ensure a level of tissue oxygenation that is commensurate with organ metabolism and function. This is evidenced in the vascular responses of the stomach to increased acid production and in intestine during periods of enhanced nutrient absorption. Complimenting the metabolic vasoregulation is a strong myogenic response that contributes to basal vascular tone and to the responses elicited by changes in intravascular pressure. The GI circulation also contributes to a mucosal defense mechanism that protects against excessive damage to the epithelial lining following ingestion of toxins and/or noxious agents. Profound reductions in GI blood flow are evidenced in certain physiological (strenuous exercise) and pathological (hemorrhage) conditions, while some disease states (e.g., chronic portal hypertension) are associated with a hyperdynamic circulation. The sacrificial nature of GI blood flow is essential for ensuring adequate perfusion of vital organs during periods of whole body stress. The restoration of blood flow (reperfusion) to GI organs following ischemia elicits an exaggerated tissue injury response that reflects the potential of this organ system to generate reactive oxygen species and to mount an inflammatory response. Human and animal studies of inflammatory bowel disease have also revealed a contribution of the vasculature to the initiation and perpetuation of the tissue inflammation and associated injury response. PMID- 26140728 TI - Let's talk about death: data collection for verbal autopsies in a demographic and health surveillance site in Malaysia. AB - BACKGROUND: Verbal autopsies have gained considerable ground as an acceptable alternative to medically determined cause of death. Unlike with clinical or more administrative settings for data collection, verbal autopsies require significant involvement of families and communities, which introduces important social and cultural considerations. However, there is very little clear guidance about the methodological issues in data collection. The objectives of this case study were: to explore the range of bereavement rituals within the multi-ethnic, multi-faith population of the district; to investigate the preparedness of communities to talk about death; to describe the verbal autopsy process; to assess the effects of collecting verbal autopsy data on data collectors; and to determine the most accurate sources of information about deaths in the community. METHODS: A case study approach was used, using focus group discussions, indepth interviews and field notes. Thematic analyses were undertaken using NVivo. RESULTS: Consideration of cultural bereavement practices is importance to acceptance and response rates to verbal autopsies. They are also important to the timing of verbal autopsy interviews. Well trained data collectors, regardless of health qualifications are able to collect good quality data, but debriefing is important to their health and well being. This article contributes to guidance on the data collection procedures for verbal autopsies within community settings. PMID- 26140729 TI - Improving district facility readiness: a 12-month evaluation of a data-driven health systems strengthening intervention in rural Rwanda. AB - BACKGROUND: While health systems strengthening (HSS) interventions are recommended by global health policy experts to improve population health in resource-limited settings, few examples exist of evaluations of HSS interventions conducted at the district level. In 2009, a partnership between Partners In Health (PIH), a non-governmental organization, and the Rwandan Ministry of Health (RMOH) was provided funds to implement and evaluate a district-level HSS intervention in two rural districts of Rwanda. DESIGN: The partnership provided limited funds to 14 health centers for targeted systems support in 2010; six others received support prior to the intervention (reference). RMOH health systems norms were mapped across the WHO HSS framework, scored from 0 to 10 and incorporated into a rapid survey assessing 11 domains of facility readiness. Stakeholder meetings allowed partnership leaders to review results, set priorities, and allocate resources. Investments included salary support, infrastructure improvements, medical equipment, and social support for patients. We compared facility domain scores from the start of the intervention to 12 months and tested for correlation between change in score and change in funding allocation to assess equity in our approach. RESULTS: We found significant improvements among intervention facilities from baseline to 12 months across several domains [infrastructure (+4, p=0.0001), clinical services (+1.2, p=0.03), infection and sanitation control (+0.6, p=0.03), medical equipment (+1.0, p=0.02), information use (+2, p=0.002)]. Composite score across domains improved from 6.2 at baseline to 7.4 at 12 months (p=0.002). Across facilities, 50% had composite scores greater than the average score among reference facilities (7.4) at 12 months compared to none at baseline. CONCLUSIONS: Rapid facility surveys, stakeholder engagement, and information feedback can be used for gap analysis and resource allocation. This approach can achieve effective use of limited resources, improve facility readiness, and ensure consistency of facility capacity to provide quality care at the district level. PMID- 26140730 TI - Extracellular localization of catalase is associated with the transformed state of malignant cells. AB - Oncogenic transformation is dependent on activated membrane-associated NADPH oxidase (NOX). However, the resultant extracellular superoxide anions are also driving the NO/peroxynitrite and the HOCl pathway, which eliminates NOX expressing transformed cells through selective apoptosis induction. Tumor progression is dependent on dominant interference with intercellular apoptosis inducing ROS signaling through membrane-associated catalase, which decomposes H2O2 and peroxynitrite and oxidizes NO. Particularly, the decomposition of extracellular peroxynitrite strictly requires membrane-associated catalase. We utilized small interfering RNA (siRNA)-mediated knockdown of catalase and neutralizing antibodies directed against the enzyme in combination with challenging H2O2 or peroxynitrite to determine activity and localization of catalase in cells from three distinct steps of multistage oncogenesis. Nontransformed cells did not generate extracellular superoxide anions and only showed intracellular catalase activity. Transformed cells showed superoxide anion dependent intercellular apoptosis-inducing ROS signaling in the presence of suboptimal catalase activity in their membrane. Tumor cells exhibited tight control of intercellular apoptosis-inducing ROS signaling through a high local concentration of membrane-associated catalase. These data demonstrate that translocation of catalase to the outside of the cell membrane is already associated with the transformation step. A strong local increase in the concentration of membrane-associated catalase is achieved during tumor progression and is controlled by tumor cell-derived H2O2 and by transglutaminase. PMID- 26140731 TI - Modeling the next generation sequencing read count data for DNA copy number variant study. AB - As one of the most recent advanced technologies developed for biomedical research, the next generation sequencing (NGS) technology has opened more opportunities for scientific discovery of genetic information. The NGS technology is particularly useful in elucidating a genome for the analysis of DNA copy number variants (CNVs). The study of CNVs is important as many genetic studies have led to the conclusion that cancer development, genetic disorders, and other diseases are usually relevant to CNVs on the genome. One way to analyze the NGS data for detecting boundaries of CNV regions on a chromosome or a genome is to phrase the problem as a statistical change point detection problem presented in the read count data. We therefore provide a statistical change point model to help detect CNVs using the NGS read count data. We use a Bayesian approach to incorporate possible parameter changes in the underlying distribution of the NGS read count data. Posterior probabilities for the change point inferences are derived. Extensive simulation studies have shown advantages of our proposed methods. The proposed methods are also applied to a publicly available lung cancer cell line NGS dataset, and CNV regions on this cell line are successfully identified. PMID- 26140732 TI - Surgical Resection of Primary Tumor in Asymptomatic or Minimally Symptomatic Patients With Stage IV Colorectal Cancer: A Canadian Province Experience. AB - BACKGROUND: Surgical resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Survival benefit reported in the literature has been attributed to the selection of younger and healthier patients with good performance status. We have recently reported that resection of the primary tumor improved survival of patients with stage IV CRC. In this study we examined survival benefit of surgery in patients with asymptomatic or minimally symptomatic primary tumor. PATIENTS AND METHODS: A cohort of patients with stage IV CRC and asymptomatic or minimally symptomatic primary tumor, who were diagnosed during the period of 1992 to 2005, in the province of Saskatchewan Canada, was evaluated. The Kaplan-Meier method was used to determine survival. A multivariate Cox proportional hazard regression analysis was performed to determine prognostic importance of resection of primary tumor. A test for interaction was performed for resection of primary tumor and other important clinicopathological variables. RESULTS: A total of 834 patients with a median age of 70 years (range, 22-93) and male:female ratio of 58:42 were identified. Among them 521 (63%) patients underwent surgery and 361 (43.3%) received chemotherapy. Patients who underwent surgery and received any chemotherapy had a median overall survival of 19.7 months (95% confidence interval [CI], 16.9-22.6) compared with 8.4 months (95% CI, 6.9-10.0) if they did not have surgery (P < .0001). In multivariate analysis, 5-fluorouracil-based chemotherapy (hazard ratio [HR], 0.43; 95% CI, 0.36-0.53), surgical resection of the primary tumor (HR, 0.47; 95% CI, 0.39-0.57), metastasectomy (HR, 0.48; 95% CI, 0.38-0.62), and second-line chemotherapy (HR, 0.72; 95% CI, 0.58-0.92) were correlated with superior survival. A test for interaction between >= 1 metastatic sites and surgery was significant, which suggests a larger benefit of surgery in patients with stage IVA disease. CONCLUSION: Results of this large population-based cohort study suggest that resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV CRC improved survival independent of other prognostic variables. The benefit was more pronounced in stage IVA disease. PMID- 26140734 TI - Mesenchymal stem cells do not exert direct beneficial effects on CNS remyelination in the absence of the peripheral immune system. AB - Remyelination is the natural repair mechanism in demyelinating disorders such as multiple sclerosis (MS) and it was proposed that it might protect from axonal loss. For unknown reasons, remyelination is often incomplete or fails in MS lesions and therapeutic treatments to enhance remyelination are not available. Recently, the transplantation of exogenous mesenchymal stem cells (MSC) has emerged as a promising tool to enhance repair processes. This included the animal model experimental autoimmune encephalomyelitis (EAE), a commonly used model for the autoimmune mechanisms of MS. However, in EAE it is not clear if the beneficial effect of MSC derives from a direct influence on brain resident cells or if this is an indirect phenomenon via modulation of the peripheral immune system. The aim of this study was to determine potential regenerative functions of MSC in the toxic cuprizone model of demyelination that allows studying direct effects on de- and remyelination without the influence of the peripheral immune system. MSC from three different species (human, murine, canine) were transplanted either intraventricularly into the cerebrospinal fluid or directly into the lesion of the corpus callosum at two time points: at the onset of oligodendrocyte progenitor cell (OPC) proliferation or the peak of OPC proliferation during cuprizone induced demyelination. Our results show that MSC did not exert any regenerative effects after cuprizone induced demyelination and oligodendrocyte loss. During remyelination, MSC did not influence the dynamics of OPC proliferation and myelin formation. In conclusion, MSC did not exert direct regenerative functions in a mouse model where peripheral immune cells and especially T lymphocytes do not play a role. We thus suggest that the peripheral immune system is required for MSC to exert their effects and this is independent from a direct influence of the central nervous system. PMID- 26140733 TI - The Prognostic Relevance of Histological Subtype in Patients With Peritoneal Metastases From Colorectal Cancer: A Nationwide Population-Based Study. AB - BACKGROUND: With evolving treatment possibilities for peritoneal metastases (PM) from colorectal cancer (CRC), adequate prognostication and patient selection for treatment becomes increasingly important. We investigated the prognostic relevance of commonly identified histological subtypes in PM of CRC (adenocarcinoma [AC], mucinous AC [MC], and signet-ring cell carcinoma [SC]), which is currently unclear. PATIENTS AND METHODS: This study involved 4277 patients diagnosed with synchronous PM from CRC between 2005 and 2012 in The Netherlands. Kaplan-Meier analysis and log-rank testing were performed to estimate survival. Subsequently a Cox proportional hazard model was used to calculate hazard ratios for the risk of death. RESULTS: Most of the CRC patients were diagnosed with AC (n = 3008; 70%), whereas MC and SC were found in 958 (22%) and 311 (7%) patients, respectively. SC was associated with the highest risk of death in colon and rectal cancer, with median survival rates of respectively, 6.6 and 6.9 months. For MC, median survival varied from 10.9 months in colon and 9.8 months in rectal cancer (P > .05). In colon cancer, MC was associated with a significantly lower risk of death compared with AC (hazard ratio, 0.9; 95% confidence interval, 0.79-0.95). In rectal cancer, no such effect was observed. AC was associated with a significantly poorer survival rate in the case of primary colonic tumor localization (7.4 months in colon vs. 10.9 months in rectal cancer). CONCLUSION: Histological subtype is an important prognostic factor in patients with synchronous PM of colorectal origin. This knowledge will aid clinicians in counseling of patients and clinical decision-making regarding possible treatment options. PMID- 26140735 TI - Impact of a maternal history of childhood abuse on the development of mother infant interaction during the first year of life. AB - The aim of this study was to examine the impact of a maternal history of abuse on mother-infant interaction (emotional availability; EA) in infancy and early toddlerhood. Over an 18-month period, women giving birth to a child in the local obstetric units were screened using the Childhood Trauma Questionnaire. Women who reported moderate or severe sexual and/or physical abuse were included in the maltreatment group (n=58; MG) and compared with a non-maltreated comparison group (n=61; CG). EA was investigated under experimental conditions when the children were 5 and 12 months of age using the Emotional Availability Scales. While mother child dyads in the MG showed only very discrete interactional alterations at an infant age of 5 months, their EA differed significantly from the CG at 12 months due to the lack of an increase in EA observed in the MG. Exploratory analyses showed an additional effect of emotional abuse on EA at 12 months. These data indicate that the period when child locomotion develops might represent a critical time window for mothers with a history of abuse. Our results constitute an advance in research on child abuse as they identify a possible time window of non-normative alteration in mother-child interaction. This period could be targeted by strategies to prevent intergenerational transmission of abusive experiences. PMID- 26140736 TI - Oral contraceptive use and incident stroke in women with sickle cell disease. AB - OBJECTIVE: Oral contraceptives increase the risk of ischemic stroke among women. However, the effect is not studied in the stroke prone sickle cell disease (SCD) population. We want to determine the rate of incident stroke among women with SCD enrolled in a large cohort with longitudinal follow-up. STUDY DESIGN: A total of 1257 women aged >=15 and <45years, enrolled in Phase 1 of Cooperative Study of SCD, underwent a baseline examination for assessment of demographics, prior medical history, laboratory assessments, and clinical data. The effects of active oral contraceptive use at baseline interview on incident ischemic and hemorrhagic strokes were assessed after adjusting for potential confounders using Cox Proportional Hazards analysis. RESULTS: A total of 178 (14.2%) of 1257 women with SCD reported use of oral contraceptives. The age adjusted annual incidence of incident stroke was four folds higher among women who reported active oral contraceptive use than those who did not report use (1.6/100 person-years versus 0.4/ 100 person-years, p=0.03). After adjusting for age, cigarette smoking status, history of exchange transfusions, alcohol use, body weight, systolic blood pressure, and heart rate, oral contraceptive use was not significantly associated with rate of ischemic stroke (hazards ratio [HR], 3.6 95% confidence interval [CI] 0.8-16.5, p=0.09) or hemorrhagic stroke (HR, 1.2 95% CI 0.2-5.7, p=0.8). CONCLUSIONS: The four fold higher risk of incident stroke associated with use of oral contraceptives in women with SCD can be mitigated by controlling other cardiovascular risk factors. IMPLICATIONS: Our results are expected to increase the awareness, among both medical practitioners and patients, regarding the four fold higher risk of incident stroke associated with use of oral contraceptives in women with SCD. Our results also identify the confounding effect of other cardiovascular risk factors such as cigarette smoking on the observed relationship and thus identify potential targets for prevention. PMID- 26140737 TI - Adherence to mechanical thromboprophylaxis after surgery: A systematic review and meta-analysis. AB - BACKGROUND: Many clinical practice guidelines, while recommending mechanical thromboprophylaxis after surgery, have raised concerns that discomfort may result in nonadherence. We therefore addressed adherence to mechanical thromboprophylaxis after surgery. METHODS: We searched MEDLINE from January 1, 2000 to May 21, 2015 for English-language observational studies that assessed patient adherence to mechanical thromboprophylaxis after surgery. We conducted a meta-analysis to estimate average adherence rates. RESULTS: We identified 8 studies (7 for compression devices, 1 for stockings) with median follow up time of 3days. The pooled estimate of adherence for compression devices was 75% (median 78%, range 40%-89%). Studies with shorter follow-up (<=3days, n=4, pooled adherence 75%) and longer follow-up (>3days, n=3, pooled adherence 75%) reported similar adherence (p=0.99). The studies varied in definitions of adherence, frequency of assessment, length of follow-up and completeness of reporting. No study followed patients after discharge. CONCLUSIONS: Up to one fourth of patients are nonadherent to mechanical thromboprophylaxis while hospitalized. Clinicians considering the relative merits of mechanical versus pharmacologic prophylaxis should address the issue of adherence. Strategies to improve adherence merit investigation. PMID- 26140724 TI - Ion Channels in the Heart. AB - Optimal cardiac function depends on proper timing of excitation and contraction in various regions of the heart, as well as on appropriate heart rate. This is accomplished via specialized electrical properties of various components of the system, including the sinoatrial node, atria, atrioventricular node, His-Purkinje system, and ventricles. Here we review the major regionally determined electrical properties of these cardiac regions and present the available data regarding the molecular and ionic bases of regional cardiac function and dysfunction. Understanding these differences is of fundamental importance for the investigation of arrhythmia mechanisms and pharmacotherapy. PMID- 26140738 TI - Is dedicated chest CT needed in addition to PET/CT for evaluation of pediatric oncology patients? AB - PURPOSE: To assess the computed tomography (CT) portion of a positron emission tomography (PET)/CT, at lower dose without breath holding, as compared to diagnostic chest CT (dCTC), performed at regular dose with breath holding, and question the necessity of both for patient care in pediatric oncology. MATERIALS AND METHODS: This retrospective study included 46 pediatric patients with histologically proven malignant tumors that had a total of 119 scans. RESULTS: A total of 29 discrepancies were found between dCTC and PET/CT reports. CONCLUSION: In the evaluation of metastatic thoracic disease in pediatric oncology patients, the non-breath holding CT portion of PET/CT has sensitivity and specificity that approaches dCTC. PMID- 26140739 TI - The effect of the addition of allopurinol on blood pressure control in African Americans treated with a thiazide-like diuretic. AB - We tested the hypothesis that xanthine oxidase inhibition among African Americans receiving the thiazide-type diuretic chlorthalidone may improve blood pressure control with fewer hyperuricemia-related side effects. We performed a randomized, double-blind, placebo-controlled study of African Americans with Stage 1 hypertension without clinically significant renal disease. One hundred fifty African American men or women between the ages of 18 and 65 years who met the exclusion/inclusion criteria with untreated or treated hypertension were started on chlorthalidone (25 mg/d) and potassium chloride. After a 5-week run-in on chlorthalidone, baseline testing was performed and they were randomized to allopurinol (300 mg/dL) or placebo with doses adjusted based on uric acid levels and followed for 8 weeks. One hundred ten subjects completed the study. Baseline systolic blood pressures after the 5-week chlorthalidone run-in were 119.9 +/- 13.6 in the allopurinol group and 117 +/- 11.2 in the placebo group indicating excellent blood pressure control with the single agent. After at least 4 week postrandomization, the difference in mean change in systolic blood pressure in allopurinol less placebo from visits 5 to 3 was 4.3 mm Hg (95% confidence interval, -0.2 to 8.7; P = .059). The difference in mean change in uric acid levels over the same period was 2.1 mg/dL (95% confidence interval, 1.7-2.6; P < .001). The use of chlorthalidone with or without allopurinol resulted in excellent blood pressure control. The addition of allopurinol tended to improve clinic blood pressure, but the difference from the group receiving chlorthalidone alone was not statistically significant. PMID- 26140741 TI - Multidisciplinary Treatment of Severe Osteogenesis Imperfecta: Functional Outcomes at Skeletal Maturity. AB - OBJECTIVE: To determine the functional outcomes associated with long-term multidisciplinary treatment, intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI types III or IV). DESIGN: Retrospective study where outcomes were measured prospectively. SETTING: Pediatric orthopedic hospital. PARTICIPANTS: Adolescents (N=41; age range, 15-21y) with severe OI (OI type III: n=17; OI type IV: n=24) who had started therapy before the age of 6 years, had received treatment for at least 10 years, and had achieved final height. INTERVENTIONS: Intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation. MAIN OUTCOME MEASURE: Pediatric Evaluation of Disability Inventory. RESULTS: At the time of the last available follow-up examination, none of the individuals diagnosed with OI type III (most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV were able to ambulate without ambulation aids. Regarding self-care, we specifically assessed 8 skills that we deemed essential for living independently (grooming; dressing; toileting; bed, chair, toilet, tub, and car transfers). Only 6 (35%) of the youths with OI type III were able to complete all 8 items, whereas 23 (96%) individuals with OI type IV managed to perform all tasks. Teens with OI type III often needed assistance for the transfer to toilet, tub, and car and for personal hygiene and clothing management associated with toileting, usually because of limitations in upper-extremity function. CONCLUSIONS: These observations suggest that further improvements in the functional status of the most severely affected children with OI are contingent on advances in the clinical management of upper-extremity issues. PMID- 26140740 TI - Greater Adipose Tissue Distribution and Diminished Spinal Musculoskeletal Density in Adults With Cerebral Palsy. AB - OBJECTIVES: To examine differences in adipose tissue distribution, lumbar vertebral bone mineral density (BMD), and muscle attenuation in adults with and without cerebral palsy (CP), and to determine the associations between morphologic characteristics. DESIGN: Cross-sectional, retrospective analyses of archived computed tomography scans. SETTING: Clinical treatment and rehabilitation center. PARTICIPANTS: Adults (N=352) with CP (age, 38.8+/-14.4y; body mass, 61.3+/-17.1kg; Gross Motor Function Classification System levels, I-V) and a matched cohort of neurotypical adults. Of the 41 adults with CP included in the study, 10 were not matchable because of low body masses. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Computed tomography scans were assessed for visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas, psoas major area and attenuation in Hounsfield units (Hu), and cortical and trabecular BMDs. RESULTS: Adults with CP had lower cortical (beta=-63.41 Hu, P<.001) and trabecular (beta=-42.24 Hu, P<.001) BMDs and psoas major areas (beta= 374.51mm(2), P<.001) and attenuation (beta=-9.21 Hu, P<.001) after controlling for age, sex, and body mass. Adults with CP had greater VAT (beta=3914.81mm(2), P<.001) and SAT (beta=4615.68mm(2), P<.001). Muscle attenuation was significantly correlated with trabecular (r=.51, P=.002) and cortical (r=.46, P<.01) BMD, whereas VAT was negatively associated with cortical BMD (beta=-.037 Hu/cm(2), r(2)=.13, P=.03). CONCLUSIONS: Adults with CP had lower BMDs, smaller psoas major area, greater intermuscular adipose tissue, and greater trunk adiposity than neurotypical adults. VAT and cortical BMD were inversely associated. PMID- 26140742 TI - Assessment of the availability of technology for trauma care in Nepal. AB - BACKGROUND: We sought to assess the availability of technology-related equipment for trauma care in Nepal and to identify factors leading to optimal availability as well as deficiencies. We also sought to identify potential solutions addressing the deficits in terms of health systems management and product development. METHODS: Thirty-two items for large hospitals and sixteen items for small hospitals related to the technological aspect of trauma care were selected from the World Health Organization's Guidelines for Essential Trauma Care for the current study. Fifty-six small and 29 large hospitals were assessed for availability of these items in the study area. Site visits included direct inspection and interviews with administrative, clinical, and bioengineering staff. RESULTS: Deficiencies of many specific items were noted, including many that were inexpensive and which could have been easily supplied. Shortage of electricity was identified as a major infrastructural deficiency present in all parts of the country. Deficiencies of pulse oximetry and ventilators were observed in most hospitals, attributed in most part to frequent breakdowns and long downtimes because of lack of vendor-based service contracts or in-house maintenance staff. Sub-optimal oxygen supply was identified as a major and frequent deficiency contributing to disruption of services. All equipment was imported except for a small percent of suction machines and haemoglobinometers. CONCLUSIONS: The study identified a range of items which were deficient and whose availability could be improved cost-effectively and sustainably by better planning and organisation. The electricity deficit has been dealt with successfully in a few hospitals via direct feeder lines and installation of solar panels; wider implementation of these methods would help solve a large portion of the technological deficiencies. From a health systems management view-point, strengthening procurement and stocking of low cost items especially in remote parts of the country is needed. From a product development view-point, there is a need for robust pulse-oximeters and ventilators that are lower cost and which have longer durability and less need for repairs. Increasing capabilities for local manufacture is another potential method to increase availability of a range of equipment and spare parts. PMID- 26140743 TI - Infiltration performance of engineered surfaces commonly used for distributed stormwater management. AB - Engineered porous media are commonly used in low impact development (LID) structures to mitigate excess stormwater in urban environments. Differences in infiltrability of these LID systems arise from the wide variety of materials used to create porous surfaces and subsequent maintenance, debris loading, and physical damage. In this study, the infiltration capacity of six common materials was tested by multiple replicate experiments with automated mini-disk infiltrometers. The tested materials included porous asphalt, porous concrete, porous brick pavers, flexible porous pavement, engineered soils, and native soils. Porous asphalt, large porous brick pavers, and curb cutout rain gardens showed the greatest infiltration rates. Most engineered porous pavements and soils performed better than the native silt loam soils. Infiltration performance was found to be related more to site design and environmental factors than material choice. Sediment trap zones in both pavements and engineered soil rain gardens were found to be beneficial to the whole site performance. Winter chloride application had a large negative impact on poured in place concrete, making it a poor choice for heavily salted areas. PMID- 26140744 TI - [Asthenia, weight loss and abdominal pain in a 64-year-old woman]. PMID- 26140745 TI - [Clinical use of D-dimer testing in venous thromboembolism]. PMID- 26140746 TI - Jararhagin-induced mechanical hyperalgesia depends on TNF-alpha, IL-1beta and NFkappaB in mice. AB - Jararhagin is a hemorrhagic metalloprotease from Bothrops jararaca snake venom. The hyperalgesic mechanisms of jararhagin were investigated focusing on the role of proinflammatory cytokines (TNF-alpha and IL-1beta) and the transcription factor NFkappaB. Intraplantar administration of jararhagin (1, 10, 100 and 1000 ng/paw) induced mechanical hyperalgesia, and increased TNF-alpha levels at 1, 3 and 5 h, and IL-1beta levels at 0.5, 1 and 3 h after its injection in the paw tissue. Pre-treatment with morphine (2, 6, 12 MUg/paw) inhibited jararhagin induced mechanical hyperagesia. The systemic or local pre-treatment with etanercept (10 mg/kg and 100 MUg/paw) and IL-1ra (30 mg/kg and 100 pg/paw) inhibited jararhagin-induced mechanical hyperalgesia. Co-administration of jararhagin (0.1 ng/paw) and TNF-alpha (0.1 pg/paw) or jararhagin (0.1 ng/paw) and IL-1beta (1 pg/paw) enhanced the mechanical hyperalgesia. The systemic or local pre-treatment with PDTC (NFkappaB inhibitor; 100 mg/kg and 100 MUg/paw) inhibited jararhagin-induced mechanical hyperalgesia as well as PDTC decreased the jararhagin-induced production of TNF-alpha and IL-1beta. Thus, these data demonstrate the involvement of pro-inflammatory cytokines TNF-alpha and IL-1beta and nuclear transcription factor NFkappaB in jararhagin-induced mechanical hyperalgesia indicating that targeting these mechanisms might contribute to reduce the pain induced by B. jararaca snake venom. PMID- 26140747 TI - Selective Protonation of Acidic Residues Triggers Opsin Activation. AB - Rhodopsin, the visual pigment in the retina, is a Class A G protein-coupled receptor (GPCR) covalently bound to retinal chromophore. In dark conditions, retinal is in the cis-isomeric state, stabilizing the rhodopsin inactive state as an inverse agonist. After light absorption, retinal undergoes an isomerization photoreaction to trans-retinal, which includes a conformational change of the receptor to its active state. In the absence of retinal, the apoprotein opsin presents a low level of constitutive activity, which depends on pH, with higher propensity of activation at acidic pH. To examine the effect and the underlying mechanism that protonation may have on opsin activation, a number of MD simulations were run varying the number and identity of acidic residues selected for protonation. Results show that the combined protonation of D83, E113, and E247 is of special relevance for the induction of receptor activation. Subsequent conformational analysis of the MD trajectories provides a structural mechanistic insight into the opsin activation process. Furthermore, because protonation seems to be a determining step in the activation of other GPCRs, the methodology and rationale used herein can be extended to mechanistic studies of GPCRs in general. PMID- 26140748 TI - Development of wavelet-ANN models to predict water quality parameters in Hilo Bay, Pacific Ocean. AB - The main objective of this study is to apply artificial neural network (ANN) and wavelet-neural network (WNN) models for predicting a variety of ocean water quality parameters. In this regard, several water quality parameters in Hilo Bay, Pacific Ocean, are taken under consideration. Different combinations of water quality parameters are applied as input variables to predict daily values of salinity, temperature and DO as well as hourly values of DO. The results demonstrate that the WNN models are superior to the ANN models. Also, the hourly models developed for DO prediction outperform the daily models of DO. For the daily models, the most accurate model has R equal to 0.96, while for the hourly model it reaches up to 0.98. Overall, the results show the ability of the model to monitor the ocean parameters, in condition with missing data, or when regular measurement and monitoring are impossible. PMID- 26140749 TI - Bioleaching of multiple metals from contaminated sediment by moderate thermophiles. AB - A moderately thermophilic consortium was applied in bioleaching multiple metals from contaminated sediment. The consortium got higher acidification and metals soubilization efficiency than that of the pure strains. The synergistic effect of the thermophilic consortium accelerated substrates utilization. The utilization of substrate started with sulfur in the early stage, and then the pH declined, giving rise to making use of the pyrite. Community dynamic showed that A. caldus was the predominant bacteria during the whole bioleaching process while the abundance of S. thermotolerans increased together with pyrite utilization. Solubilization efficiency of Zn, Cu, Mn and Cd reached 98%, 94%, 95%, and 89% respectively, while As, Hg, Pb was only 45%, 34%, 22%. Logistic model was used to simulate the bioleaching process, whose fitting degree was higher than 90%. Correlation analysis revealed that metal leaching was mainly an acid solubilization process. Fraction analysis revealed that metals decreased in mobility and bioavailability. PMID- 26140750 TI - Environmental factors modulating the extent of impact in coastal invasions: The case of a widespread invasive caprellid (Crustacea: Amphipoda) in the Iberian Peninsula. AB - Understanding the respective roles of environment and interspecific interactions in shaping species' distributions is a critical aspect in determining the potential impacts of newcomer species on occupied habitats. The invasive caprellid amphipod Caprella scaura has successfully spread along southern Europe in a short time period, coinciding with a decline in the population of an ecologically similar congener, Caprella equilibra. To understand the mechanisms underlying the establishment success of this aggressive species and its potential role in shaping C. equilibra's distribution, we analyze the biotic and abiotic factors involved in the patterns of distribution and co-occurrence of both species along the Iberian Peninsula and northern Africa. Our analyses support that C. scaura is competitively displacing C. equilibra from the study area, but also point out the critical role of salinity and temperature in modulating this interaction and limiting the invasive success of C. scaura on the Iberian North Atlantic coast. PMID- 26140751 TI - Reaching Forward. PMID- 26140752 TI - 50th Anniversary Landmark Perspective on Sterns LP, Ferlic RM, Lillehei CW. Cardiovascular Surgery in Infancy: Ten-Year Results From the University of Minnesota Hospitals. Ann Thorac Surg 1965;1:519-31. 1965. PMID- 26140753 TI - 50th Anniversary Landmark Commentary on Loop FD, Spampinato N, Cheanvechai C, Effler DB. The Free Internal Mammary Artery Bypass Graft: Use of the IMA in the Aorto-to-Coronary Artery Position. Ann Thorac Surg 1973;15:50-5. PMID- 26140754 TI - 50th Anniversary Landmark Commentary on Rein JG, Freed MD, Norwood WI, Castaneda AR. Early and Late Results of Closure of Ventricular Septal Defect in Infancy. Ann Thorac Surg 1977;24:19-27. PMID- 26140755 TI - 50th Anniversary Landmark Commentary on Grillo HC. Tracheal Tumors: Surgical Management. Ann Thorac Surg 1978;26:112-25. PMID- 26140756 TI - Invited Commentary. PMID- 26140757 TI - Invited Commentary. PMID- 26140758 TI - Invited Commentary. PMID- 26140759 TI - Invited Commentary. PMID- 26140760 TI - Invited Commentary. PMID- 26140761 TI - Invited Commentary. PMID- 26140762 TI - Invited Commentary. PMID- 26140763 TI - Invited Commentary. PMID- 26140764 TI - Invited Commentary. PMID- 26140765 TI - Invited Commentary. PMID- 26140766 TI - Invited Commentary. PMID- 26140767 TI - Invited Commentary. PMID- 26140768 TI - Invited Commentary. PMID- 26140769 TI - Lung Cancer With Tumor Emboli. AB - We report a case of squamous cell lung carcinoma that invaded the left atrium through the left pulmonary vein. This patient had two episodes of systemic embolism before diagnosis. The second episode was treated with embolectomy, and the pathology analysis showed squamous cell carcinoma. The tumor was surgically resected, using cardiopulmonary bypass to resect the intracardiac portion. We discuss causes of tumor emboli in lung cancer and surgical treatment. PMID- 26140770 TI - High-Dose Intravenous Octreotide Is Safe and May Be Superior to Surgery in Managing Severe Postesophagectomy Chylothorax in High-Risk Patients. AB - Postesophagectomy chylothorax is a relatively rare but potentially lethal complication. Management can be challenging, especially of patients after radiotherapy. Chest tube drainage, bowel rest, total parenteral nutrition, and adequate fluid replacement are the preferred first-line treatment. Thoracic duct band ligation is the approach of last resort; however, surgical reexploration is often not an option in these patients. The use of octreotide to control chylothorax in adults has been reported, but mainly when given in low subcutaneous doses. We report the successful use of high intravenous doses of octreotide to manage large postesophagectomy chylothorax in an adult after failed band ligation. PMID- 26140771 TI - Spontaneous Hemothorax Caused by Pulmonary Micro-Venous Hemangioma. AB - Various etiologies of spontaneous hemothorax have been reported, though the cause remains unidentified in some patients despite an exploratory thoracotomy. We report on an 89-year-old man with spontaneous hemothorax resolved by partial resection of the lung using complete video-assisted thoracoscopic surgery. The histopathologic findings revealed a ruptured micro-venous hemangioma located just below the bleeding visceral pleura. To the best of our knowledge, this is the first report of spontaneous hemothorax caused by a pulmonary micro-venous hemangioma. PMID- 26140772 TI - A Giant Purely Polypoid Esophageal Leiomyoma. AB - We present a case of a giant (13-cm length) purely polypoid esophageal leiomyoma without any intramural development. This form of leiomyoma is rare and develops due to proliferation originating from the muscularis mucosae, although the intramural type originates in the muscularis propria. This should not be confused with giant fibrovascular polyps, which are postulated to arise at the pharyngoesophageal junction when a flap of mobile, redundant submucosa prolapses distally and may cause asphyxia when protruding into the mouth. Our case was successfully removed by a right thoracotomy. PMID- 26140773 TI - A 1-Year-Old Boy With Paraspinal Elastofibroma: The Youngest Diagnosed Elastofibroma. AB - Elastofibroma is a benign and slow-growing soft tissue tumor that classically presents as an ill-defined solitary mass at the inferior pole of the scapula in the fifth and sixth decades of life for women. This tumor can be rarely seen in childhood, but it has not been reported in the infantile age group to date. To our knowledge, this case represents the first report of elastofibroma in the infantile age group. The aim of this report is to present a paravertebral elastofibroma in a 14-month-old patient and discuss the clinical features and treatment modalities. PMID- 26140774 TI - Endograft as Bridge to Open Repair for Ruptured Thoracic Aneurysm in a Pregnant Marfan Patient. AB - Women with Marfan syndrome are at increased risk of aortic events during pregnancy. We present the case of a ruptured descending thoracic aortic aneurysm in a woman with Marfan syndrome who was 25 weeks pregnant. Emergent intervention was performed using an endovascular repair as a bridge to allow continuation of pregnancy, decreasing fetal morbidity, and allow subsequent later definitive open aortic repair. PMID- 26140775 TI - Transeptal Aortic Valve Replacement After Arterial Switch in a Patient With Taussig-Bing Anomaly. AB - Aortic valve replacement in patients after arterial switch is technically difficult, especially in patients with small aorta without neoaortic regurgitation. We report a patient with Taussig-Bing anomaly who had fungal endocarditis after several cardiac operations and was successfully treated with transeptal aortic valve replacement concomitant with other surgical and medical treatments. PMID- 26140776 TI - Left Ventricular Myxoma Occluding the Suprarenal Abdominal Aorta in an Infant. AB - Myxoma is the most common primary cardiac tumor in adults; however, it is extremely rare in infants. Acute occlusion of the abdominal aorta by a cardiac myxoma is also rare. We report the case of an infant with acute occlusion of the suprarenal abdominal aorta by a left ventricular myxoma. The patient underwent successful catheter embolectomy of the abdominal aorta and surgical resection of the cardiac myxoma. This is a very rare case report of the combination of infantile left ventricular myxoma and acute occlusion of the abdominal aorta. PMID- 26140777 TI - Thrombus in the Proximal Aorta: Cardiopulmonary Bypass Strategy and Surgical Management. AB - De novo noninfective thrombus formation in the ascending aorta is rare. We report two cases of ascending aortic thrombus, their surgical management, and cardiopulmonary bypass strategy. PMID- 26140778 TI - Factor VIIa for Annulus Rupture After Transcatheter Aortic Valve Replacement. AB - Over the last decade, transcatheter aortic valve replacement (TAVR) has emerged as an effective treatment for inoperable and selected high surgical-risk patients with aortic stenosis. However, management of procedural complications with TAVR represents a major challenge as most TAVR patients carry prohibitive or high-risk of mortality with open surgical conversion. Here we present a case of TAVR complicated by aortic annulus rupture that was successfully managed nonoperatively by pericardial drainage, blood product transfusion, and adjunctive administration of recombinant activated factor VIIa. PMID- 26140779 TI - Acute Aortic Dissection Extending Into the Lung. AB - The radiologic manifestations of ruptured acute aortic dissection, Stanford type A aortic dissection, DeBakey type 1 can present in different radiographic scenarios with devastating outcomes. Here, we present a rare case of a 70-year old man who presented to the emergency department with chest pain radiating to the back. A chest computed tomography scan showed a Stanford type A, DeBakey type 1, acute aortic dissection ruptured into the aortopulmonary window and stenosing the pulmonary trunk, both main pulmonary arteries, and dissecting the bronchovascular sheaths and flow into the pulmonary interstitium, causing pulmonary interstitial hemorrhage. The patient underwent emergent ascending aorta replacement with hemiarch replacement with circulatory arrest. The postoperative course was unremarkable. PMID- 26140780 TI - Migration of Amplatzer Septal Occluder to the Deep Aortic Arch in a Patient With Multiple Anatomic Anomalies. AB - Atrial septal defect closure using the Amplatzer septal occluder (AGA Medical Corp, Golden Valley, MN) device is an established treatment option with excellent clinical outcome. However, several structural characteristics have been reported to be prognostic factors for failure of catheter interventional treatment. We report successful surgical removal of an Amplatzer septal occluder that had become dislocated and had migrated into the deep aortic arch. Compatible with previous reports, the patient presented with an atrial septal defect complicated by multiple anatomic deformities that were considered to be a contraindication for interventional treatment. Detailed structural assessment of the atrial septal defect is mandatory for successful treatment using the Amplatzer septal occluder. PMID- 26140781 TI - Thymic Cavernous Hemangioma With a Left Innominate Vein Aneurysm. AB - Here we report a case of thymic cavernous haemangioma with the left innominate vein aneurysm. A 43-year-old man presented with chest pain. Enhanced chest computed tomography revealed an anterior mediastinal tumor measuring 60 * 52 * 38 mm with multiple venous lakes and focal specks of calcification, composed of a low-density soft tissue mass along with a left innominate vein aneurysm. We preoperatively diagnosed the mass as a thymic hemangioma and subsequently performed surgical resection. Pathologic diagnosis was a thymic cavernous hemangioma with a left innominate vein aneurysm, which is very rare. PMID- 26140782 TI - Giant Cardiac Cavernous Hemangioma. AB - We report the case of an asymptomatic giant cardiac cavernous hemangioma in a 71 year-old man. The intracardiac mass was discovered incidentally during surveillance for his prostate cancer; however, the patient initially declined intervention. On presentation to our institution 7 years later, the lesion had enlarged significantly, and the patient consented to excision. At surgery, an 8 * 6.5 * 4.8 cm intracardiac mass located on the inferior heart border was excised with an intact capsule through a median sternotomy approach. The patient had an uneventful postoperative course. We discuss the diagnostic workup, treatment, and characteristics of this rare cardiac tumor. PMID- 26140783 TI - Delayed Diagnosis of Q Fever: Finally Diagnosed After Elective Cardiac Surgery. AB - Q fever is a bacterial infection caused by Coxiella burnetti. It can cause both acute and chronic illness. Chronic QF can present as a variety of clinical syndromes. A common and critical manifestation is endocarditis which can present atypically and is easily missed. This case describes a man who, after extensive investigation for splenomegaly and pancytopenia by several specialties, was finally diagnosed with Q fever endocarditis after unexpected aortic valve abnormalities found during elective cardiac surgery. Several factors contributed to diagnostic delay including aspects of clinical assessment and radiologic findings. Vigilance is essential for diagnosis and prompt initiation of effective treatment. PMID- 26140784 TI - Ollier Disease With Sole Chest Wall Involvement. PMID- 26140785 TI - Histologic Evidence of Transmurality Four Years After Bipolar Radiofrequency Cox Maze IV. PMID- 26140786 TI - Asymptomatic Pulmonary Venous Aneurysm Within Lung Cyst. PMID- 26140787 TI - Late Postpneumonectomy Death From Stump Thrombus. PMID- 26140788 TI - A Simple Device for Morphofunctional Evaluation During Aortic Valve-Sparing Surgery. AB - Valve-sparing operations for the treatment of aortic root disease with a structurally normal aortic valve are increasingly performed as they avoid prosthesis-related complications. Short- and long-term results are critically dependent on perfect intraoperative restoration of valve anatomy and function. Residual aortic regurgitation is the main cause of early failure, and it is the most common motive for reoperation. However, intraoperative morphofunctional valve assessment requires expertise, and only transesophageal echocardiography can provide reliable information. We describe a simple, economic, reproducible hydrostatic test to intraoperatively evaluate valve competency under direct visualization. PMID- 26140789 TI - Simultaneous Repair of Right-Sided Coarctation and Vascular Ring. AB - We present the case of a 4-year old girl with posterior fossa-hemangioma-arterial lesions-cardiac abnormalities/coarctation-eye abnormalities (PHACE) syndrome, an atypical, long-segment, right-sided coarctation of the aorta and vascular ring secondary to an aberrant left subclavian artery and left ligamentum. Simultaneous repair of both lesions was accomplished using a novel technique that included reimplantation of the aberrant left subclavian artery and translocation of the descending aorta to the proximal ascending aorta. PMID- 26140790 TI - Is Multiple Bilateral Thoracic Anomaly Different From Poland's Syndrome? PMID- 26140791 TI - The Spiritual Experience of a Surgeon. PMID- 26140792 TI - Reply: To PMID 24630765. PMID- 26140793 TI - Which Factors Should We Consider to Evaluate Relationship Between Transfusion and Morbidity After Cardiac Operations? PMID- 26140794 TI - Reply: To PMID 25440265. PMID- 26140795 TI - Aortic Valve Stenosis in Redo Operations in Octogenarians: Transcatheter Aortic Valve Implantation or Surgical Intervention? That Is the Question. PMID- 26140796 TI - Reply: To PMID 25195546. PMID- 26140797 TI - Contemporary Bloodletting in Cardiac Surgical Patients. PMID- 26140798 TI - Reply: To PMID 25583464. PMID- 26140799 TI - Bilateral Lung Transplantation From a Donor With Heparin-Induced Thrombocytopenia. AB - We report the case of a 46-year-old male patient with a history of cystic fibrosis who received bilateral lung transplantation from a donor who died secondary to complications of heparin-induced thrombocytopenia. Postoperatively, he exhibited transient focal neurologic deficits and radiographic evidence of multiple cortical and subcortical infarctions. He was treated with a combination of fondaparinux and standard immunosuppressive therapy, made a full recovery, and experienced significantly improved lung function compared to pretransplantation capacity. PMID- 26140800 TI - Treatment of Wolff-Parkinson-White Syndrome With a Thoracoscopic Surgical Procedure. AB - Thoracoscopic surgery for the treatment of Wolff-Parkinson-White syndrome is rare. We report a case of thoracoscopic surgical ablation of the epicardial pathway in a 13-year-old female patient. Intraoperative electroanatomic mapping was performed to identify the exact location of accessory electrical conduction in the right atrioventricular groove. Stamping ablation using a bipolar radiofrequency pen device achieved irreversible disappearance of the delta wave. Eight months after the surgical procedure, there has been no recurrence of arrhythmia in this patient. PMID- 26140801 TI - Hypoplastic Left Heart Syndrome With Right Ventricle Compression. AB - A male neonate presented with the aortic atresia-mitral stenosis (AA-MS) variant of hypoplastic left heart syndrome (HLHS) wherein the suprasystemic left ventricular (LV) pressure and large left ventricle shifted the intraventricular septum. A compressed right ventricle made it difficult to maintain stroke volume. To avoid high right ventricular (RV) volume load and output, we used a 2-stage Norwood-Glenn (NW-G) procedure. Bilateral pulmonary artery banding (bPAB) was performed on day of life (DOL) 4. On DOL 58, we performed percutaneous balloon dilation of the bPAB portion. At age 3 months, the NW-G procedure was performed without peripheral pulmonary hypoplasia. The patient is currently doing well. PMID- 26140802 TI - Migration of a Glenohumeral Steinmann Pin Into the Thoracic Cavity. PMID- 26140803 TI - Transvenous Implantation of a Stent Valve for Calcified Native Mitral Stenosis. AB - We used a modified combination of the transseptal and transapical methods to facilitate the controlled delivery and use of a stent valve in a patient with calcified native mitral stenosis. A loop from the right femoral vein passing transseptally and then through the apex of the left ventricle was created, enabling highly controlled positioning and deployment of the stent valve. PMID- 26140804 TI - Invasive Methicillin-Resistant Staphylococcus Aureus Endocarditis Resulting in Right Ventricular Pseudoaneurysm and Fistulation to Previous Bypass Graft. AB - We describe the case of a 73-year-old man with methicillin-resistant Staphyloccocus aureus (MRSA) endocarditis, which developed into a right ventricular pseudoaneurysm that fistulated into a previous saphenous vein graft to his distal right coronary artery (RCA). The patient was taken for a redo sternotomy, surgical evacuation of the abscess, bovine pericardial patch reconstruction of the right ventricular free wall, and tricuspid valve repair. Despite our best efforts and a repair that appeared sufficient at the time of operation, the patient died of ischemic colitis on postoperative day 5. This case report highlights some of the surgical considerations for such a rare and lethal condition. PMID- 26140805 TI - Anomalous Left Coronary From the Pulmonary Artery Presenting as Ventricular Fibrillation After Persistent Ductus Arteriosus Ligation. AB - An anomalous left coronary artery from the pulmonary artery (ALCAPA) is rarely associated with persistent ductus arteriosus (PDA). A large PDA can maintain perfusion in the left coronary artery, delaying presentation. Assessing the origin of the coronary arteries before PDA ligation is difficult, often being performed in very small or even preterm babies. We present the case of a 5-month old infant with echocardiographic features of mitral regurgitation and subendocardial ischemia who experienced ischemia and cardiac arrest after PDA ligation. Transesophageal echocardiography demonstrated ALCAPA, and left coronary translocation was performed. The infant was discharged after 10 days. PMID- 26140807 TI - Socioeconomically Disadvantaged CMS Beneficiaries Do Not Benefit From the Readmission Reduction Initiatives. AB - We assessed the impact of minority and socioeconomic status on 30-day readmission rates after 3825 primary total hip arthroplasty (THA) and 3118 primary total knee arthroplasty (TKA) procedures. Minority patients had higher THA (7.4% vs 3.2%, P=0.001) and TKA (5.4% vs 3.7%, P<0.001) readmission rates. Low socioeconomic status was associated with higher THA (6.0% vs 3.1%, P<0.001) and TKA (6.3% vs 3.8%, P=0.02) readmission rates. Risk reduction initiatives were effective after TKA, but minority status and low socioeconomic status were still associated with higher 30-day readmission rates (4.6% vs 1.8%, P<0.01). Focused postoperative engagement for Centers for Medicare and Medicaid Services (CMS) beneficiaries less than 65 years of age may help reduce complications and 30-day readmissions. PMID- 26140806 TI - The effect of bronchodilators on forced vital capacity measurement in patients with idiopathic pulmonary fibrosis. AB - BACKGROUND: Forced vital capacity (FVC) is a key measure of disease severity in patients with idiopathic pulmonary fibrosis (IPF) and is an important clinical trial endpoint. We hypothesize that reversible airflow limitation co-exists in a subgroup of patients with IPF, and that bronchodilator use will improve the performance characteristics of FVC. METHODS: IPF patients with pre and post bronchodilator spirometry testing performed were identified from two tertiary referral cohorts. The difference between pre and post-bronchodilator FVC (intra test difference) was calculated. The test characteristics of pre and post bronchodilator FVC change over time (inter-test difference) were assessed in patients with sequential spirometry, and were used to generate sample size estimates for hypothetical clinical trials using change in FVC as the primary endpoint. RESULTS: There were 551 patients, contributing 967 unique spirometry tests. The mean intra-test increase in FVC with bronchodilator use was 0.04 L (2.71 vs. 2.75 L, p < 0.001). Reversible airflow limitation (increase in FEV1 or FVC of >=12% and >=200 mL) occurred in 9.1% of patients. The inter-test difference in change in FVC over time were equivalent for pre and post bronchodilator (p = 0.65), leading to similar sample size estimates in a hypothetical clinical trial using change in FVC as the primary endpoint. CONCLUSION: Approximately one in ten patients with IPF has physiological evidence of reversible airflow limitation, and bronchodilator use in these patients may improve the assessment of disease progression based on FVC change over time. Bronchodilator use does not appear to meaningfully impact the precision of FVC as an endpoint in clinical trials. PMID- 26140809 TI - Primary disease recurrence after single lung transplantation in a patient with prior hard metal exposure. PMID- 26140819 TI - Considerations for comparative tobacco product assessments based on smoke constituent yields. AB - Cigarette smoke is a complex mixture of more than 8000 smoke constituents. The quantification of selected mainstream smoke constituent yields is one of the methods to evaluating and comparing the performance of different products. Numerous regulatory and scientific advisory bodies have used cigarette smoke constituent yield data for reporting and product comparison purposes. For more than a decade limitations of the indiscriminate application of traditional statistical methods such as the t-test for differences in comparative smoke constituent yield assessments lacking a specific study design, have been highlighted. In the present study, the variability of smoke constituent yields is demonstrated with data obtained under the ISO smoking regime for the Kentucky reference cigarette 3R4F and one commercial brand, analyzed on several occasions between 2007 and 2014. Specifically it is shown that statistically significant differences in the yields of selected smoke constituents do not readily translate to differences between products, and that tolerances need to be defined. To this end, two approaches have been proposed in the literature--minimal detectable differences, and the statistical equivalence. It is illustrated how both approaches provide more meaningful comparison outcomes than the statistical t test for differences. The present study provides considerations relevant for comparative tobacco product assessments both in the scientific and regulatory contexts. PMID- 26140808 TI - The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model. AB - BACKGROUND: Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model. METHODS: Hearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non-anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating score, and inflammatory markers 120 minutes or 24 hours post-transplant. RESULTS: MitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondrial DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient. CONCLUSIONS: IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury. PMID- 26140820 TI - Implementation of toxicokinetics in toxicity studies--Toxicokinetics of 4 methylanisole and its metabolites in juvenile and adult rats. AB - The current risk assessment of compounds is generally based on external exposure and effect relationships. External doses are often not representative for internal exposure concentrations. The aim of this study was to show how the implementation of toxicokinetics in a scheduled toxicity study contributes to improved data interpretation without additional use of animals and to the three goals of the 3R principles for animal testing. Toxicokinetic analyses were implemented in a rat developmental immunotoxicity study with 4-methylanisole without interfering with the outcome of the study and without the use of additional animals. 4-Methylanisole and its metabolites were analysed in plasma of adult rats and in pups at postnatal day 10. 4-Methylanisole has a short half life in adult animals and the plasma concentrations increased more than proportional with increasing dose. The metabolic profile appeared to be different at low dose as compared to high dose. This information on the dose proportionality of the internal exposure is crucial for the interpretation of the toxicity data and helps to identify the toxic agent and the appropriate dose metric. The metabolism was similar in adult and juvenile animals. Large inter individual variability in adult animals, as observed for 4-methylanisole, may hamper dose-response analyses of the results. In addition, 4-metylanisole was excreted via milk, but concentrations in the juvenile animals appeared to be 20- to 100-fold lower than via direct gavage exposure. The toxicokinetic parameters support the data interpretation, among others by providing better insight into internal exposures. Subsequently, it will help to prevent testing of irrelevant exposure scenarios and exposure concentrations. Overall, implementation of kinetics with limited effort provides useful information to support the interpretation of toxicological data and can contribute to reduction and refinement of animal testing. PMID- 26140822 TI - Translating Neurogenomics Into New Medicines. AB - Brain disorders remain one of the defining challenges of modern medicine and among the most poorly served with new therapeutics. Advances in human neurogenetics have begun to shed light on the genomic architecture of complex diseases of mood, cognition, brain development, and neurodegeneration. From genome-wide association studies to rare variants, these findings hold promise for defining the pathogenesis of brain disorders that have resisted simple molecular description. However, the path from genetics to new medicines is far from clear and can take decades, even for the most well-understood genetic disorders. In this review, we define three challenges for the field of neurogenetics that we believe must be addressed to translate human genetics efficiently into new therapeutics for brain disorders. PMID- 26140821 TI - Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta Analysis of Cohort Studies and Experimental Sleep Deprivation. AB - BACKGROUND: Sleep disturbance is associated with inflammatory disease risk and all-cause mortality. Here, we assess global evidence linking sleep disturbance, sleep duration, and inflammation in adult humans. METHODS: A systematic search of English language publications was performed, with inclusion of primary research articles that characterized sleep disturbance and/or sleep duration or performed experimental sleep deprivation and assessed inflammation by levels of circulating markers. Effect sizes (ES) and 95% confidence intervals (CI) were extracted and pooled using a random effect model. RESULTS: A total of 72 studies (n > 50,000) were analyzed with assessment of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha). Sleep disturbance was associated with higher levels of CRP (ES .12; 95% CI = .05-.19) and IL-6 (ES .20; 95% CI = .08 .31). Shorter sleep duration, but not the extreme of short sleep, was associated with higher levels of CRP (ES .09; 95% CI = .01-.17) but not IL-6 (ES .03; 95% CI: -.09 to .14). The extreme of long sleep duration was associated with higher levels of CRP (ES .17; 95% CI = .01-.34) and IL-6 (ES .11; 95% CI = .02-20). Neither sleep disturbances nor sleep duration was associated with TNFalpha. Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNFalpha. Some heterogeneity among studies was found, but there was no evidence of publication bias. CONCLUSIONS: Sleep disturbance and long sleep duration, but not short sleep duration, are associated with increases in markers of systemic inflammation. PMID- 26140823 TI - Evaluating changes in judgmental biases as mechanisms of cognitive-behavioral therapy for social anxiety disorder. AB - Reductions in judgmental biases concerning the cost and probability of negative social events are presumed to be mechanisms of treatment for SAD. Methodological limitations of extant studies, however, leave open the possibility that, instead of causing symptom relief, reductions in judgmental biases are correlates or consequences of it. The present study evaluated changes in judgmental biases as mechanisms explaining the efficacy of CBT for SAD. Participants were 86 individuals who met DSM-IV-TR criteria for a primary diagnosis of SAD, participated in one of two treatment outcome studies of CBT for SAD, and completed measures of judgmental (i.e., cost and probability) biases and social anxiety at pre-, mid-, and posttreatment. Treated participants had significantly greater reductions in judgmental biases than not-treated participants; pre-to post changes in cost and probability biases statistically mediated treatment outcome; and probability bias at midtreatment was a significant predictor of treatment outcome, even when modeled with a plausible rival mediator, working alliance. Contrary to hypotheses, cost bias at midtreatment was not a significant predictor of treatment outcome. Results suggest that reduction in probability bias is a mechanism by which CBT for SAD exerts its effects. PMID- 26140824 TI - Psychological Aspects of Genetic Counseling: XIII. Empathy and Decency. AB - The issues confronting genetic counselees, the demands of the "new genetics" and other factors suggest strongly the need for greater attention to counseling procedures which convey understanding of clients and help them feel more hopeful and more capable of dealing with their life problems. This should include interventions to help them feel more effective in their coping efforts as well as such ego-bolstering techniques as the expression of kindness, the provision of appropriate rewards, and other attempts to raise the client's self-esteem. These attempts should be a standard part of all genetic counseling. The traditional arguments of potential harm and time limitations often used to avoid counseling efforts are viewed through the lens of countertransference. PMID- 26140825 TI - Genetic Counseling-Stress, Coping, and the Empowerment Perspective. AB - Historically one of the basic foundations of the genetic counseling process has been nondirectiveness; however, its definition and utility continues to be in question. There remains a need to develop genetic counseling interventions in order to qualify, quantify, measure, and enhance the genetic counseling process as well as to delineate the complex interactions of education and counseling that occur. We propose a framework for genetic counseling interventions utilizing an empowerment perspective and Lazarus and Folkman's adaptation of the theory of stress and coping. This model frames the genetic counseling process as one that promotes the autonomy of the individual by providing the individual with the tools required to make their own decisions and enhances coping and adjustment to the outcome of those decisions through control and mastery. PMID- 26140826 TI - Case Report-Loyalty, Legacy, and Ledger: Contextual Therapy in a Patient with a Family History of Ovarian Cancer. AB - A client's emotional experiences and reactions to those experiences are influenced by his/her family of origin and direct or indirect interactions with various family members. Contextual therapists propose that a client's satisfaction with a relationship depends on the equity of his/her emotional interactions with family members. When relationships are inequitable, trust between individuals disintegrates. In order to reestablish trust in a relationship, a balance of interests must be restored. If not, imbalances may be passed down to future generations. A case of a woman with a family history of ovarian cancer is reviewed with the principles of contextual therapy in mind. In her family, several legacies have resulted in unbalanced relationships between family members that lead to difficulty in establishing trust within the genetic counseling session. PMID- 26140827 TI - Abstracts from the Eighteenth Annual Education Conference of the National Society of Genetic Counselors (Oakland, California, October 1999). PMID- 26140828 TI - Lesions of the Broad Ligament: A Review. AB - The differential diagnosis of lesions arising in the broad ligament is quite large. Many of these lesions can be clinically interpreted before surgery as adnexal or uterine neoplasms. Although some lesions are similar to those arising in other mullerian sites, there are unique lesions as well. The lesions are uncommon and may prove challenging to clinicians. The purpose was to review the scope of lesions affecting the broad ligament. A literature review was conducted. A Medline search was performed using the terms broad ligament, mesosalpinx, and mesovarium. A review of the scope of broad ligament lesions is presented to assist in developing a differential diagnosis if a patient with such a lesion is encountered. PMID- 26140829 TI - Change in Pain and Quality of Life Among Women Enrolled in a Trial Examining the Use of Narrow Band Imaging During Laparoscopic Surgery for Suspected Endometriosis. AB - STUDY OBJECTIVE: To examine whether the addition of narrow band imaging (NBI) to traditional white light imaging during laparoscopic surgery impacts pain and quality of life (QOL) at 3 and 6 months after surgery among women with suspected endometriosis and/or infertility. DESIGN: A randomized controlled trial (Canadian Task Force classification level I). SETTING: The trial was conducted in 2 medical centers. PATIENTS: From October 2011 to November 2013, 167 patients undergoing laparoscopic examination for suspected endometriosis and/or infertility were recruited. The analytic study sample includes 148 patients with pain and QOL outcome data. INTERVENTIONS: Patients were randomized in a 3:1 ratio to receive white light imaging followed by NBI (WL/NBI) or white light imaging only (WL/WL). MEASUREMENTS AND MAIN RESULTS: Questionnaires were administered at baseline and at 3- and 6-month follow-up time points. Average and most severe pain at each time point were assessed using a 10-cm visual analog scale. QOL was measured using the Endometriosis Health Profile-30. Baseline characteristics were similar for the study groups. The WL/NBI and WL/WL groups had similar reductions in pain at 3 and 6 months. In addition, QOL improved similarly for both the WL/NBI and WL/WL groups at 3 and 6 months. CONCLUSION: Laparoscopic surgery for suspected endometriosis is associated with a reduction in pain and an improvement in QOL. The differences in pain reduction and QOL improvement, which are noted at 3 months and remain stable at 6 months after surgery, are similar for those undergoing surgery with WL/NBI compared with those undergoing surgery under traditional white light conditions. PMID- 26140830 TI - Structured Hysteroscopic Evaluation of Endometrium in Women With Postmenopausal Bleeding. AB - STUDY OBJECTIVE: To evaluate visual pattern parameters obtained with hysteroscopy for the prediction of endometrial cancer, to evaluate observer variation of these parameters, and to present a scoring system of the parameters for the prediction of malignancy compared with subjective evaluation. DESIGN: A prospective controlled study (Canadian Task Force classification II-1). SETTING: A university clinic. PATIENTS: One hundred forty-nine consecutive women with postmenopausal bleeding and an endometrium thickness >= 5 mm. Sixty-one (41%) had endometrial cancer. Forty-six of 149 women were referred based on suspected malignancy. INTERVENTIONS: Endometrial pattern characteristics for endometrial cancer were evaluated in hysteroscopic video clips. The reference standard was pathologic evaluation of resectoscopic samples or hysterectomy. Using multivariate logistic regression, image parameters were correlated with the presence of endometrial cancer. A scoring system of visual parameters for the prediction of malignancy was compared with subjective evaluation of malignancy. MEASUREMENTS AND MAIN RESULTS: A score for lesion surface, necrosis, and vessels had an area under the curve (AUC) of 0.89, 0.89, and 0.87, respectively. A hysteroscopic cancer (HYCA) scoring system based on unsmooth lesion surface, papillary projections, surface necrosis, "candy floss" necrosis, white hyperintense spots, irregular branching vessels, and irregular distribution of irregular vessels was able to predict cancer (AUC = 0.964) with higher accuracy than subjective evaluation (AUC = 0.859, p < .01). At a score value >= 3, sensitivity was 89% and specificity was 92% with moderate agreement between observers (kappa = 0.56 [0.42-0.71]). CONCLUSION: A systematic pattern evaluation of optimal parameters by a HYCA scoring system based on systematically defined terms may increase accuracy in the diagnosis of endometrial cancer and should be further elaborated and external validity tested in unselected women with postmenopausal bleeding. PMID- 26140831 TI - Praziquantel efficacy against Brachylaima sp. metacercariae (Trematoda: Brachylaimidae) parasitizing the edible landsnail Cornu aspersum and its HPLC MS/MS residue determination. AB - Cornu aspersum is a terrestrial edible snail, often parasitized by Brachylaima (Trematoda) metacercariae. Ingestion of undercooked snails by humans allows metacercariae to develop to adult in the intestine causing brachylaimiasis (expected mortality rate 5-10%). The cosmopolitan character of the trematode and of its vector, enhanced in a future climate change scenario, and the absence of adequate sanitary controls of the snails in marketplaces clearly increase the risk of human brachylaimiasis. The treatment of farmed snails with praziquatel (PZQ) would be a tool to control this food-borne disease. The objectives of this study were: to report the prevalence of Brachylaima metacercariae parasitizing C. aspersum in marketplaces, to assess the efficacy and tolerance of PZQ in C. aspersum and to develop an HPLC-MS/MS analytical method to quantify PZQ residue in the edible snail (the acceptable daily intake of PZQ is 0.17 mg/kg bw in humans). Prevalence of parasitization of C. aspersum by Brachylaima metacercariae in public marketplaces reached the 80%. PZQ was orally administered to snails, mixed with the usual snail food. In dose determination assays three doses were individually tested (10 days): 1.2 mg PZQ/snail, 1.8 mg PZQ/snail (efficacy 97.3%, p < 0.001) and 2.4 mg PZQ/snail (efficacy 98.7%, p < 0.001). In dose confirmation tests (n = 200) the 2.4 mg PZQ/snail dose was group tested (10 snails/box, 7 days): 2 g of PZQ supplemented snail food were disposed daily in the treatment group boxes and 2 g of snail food (placebo) in the control boxes (efficacy 94.6%, p < 0.001; prevalence dropped from 68.7% in control group to 10.1% in treatment group, p < 0.001). Received dose was 220.2 mg PZQ/kg snail with shell. In the analytical method, linearity, lower limit of quantification (0.05 MUg/ml), selectivity, carry over, accuracy, precision, dilution integrity, matrix effect and stability were tested. Sixty snails were treated (11 mg PZQ/g snail food) and analyzed. PZQ was detected and quantified (0.093 mg PZQ/g snail). PZQ treatment of C. aspersum is effective, well tolerated by the snail, affordable and easy to reproduce in snail farms. PMID- 26140833 TI - Adverse Childhood Experiences, the Medical Home, and Child Well-Being. AB - OBJECTIVES: To examine the relationship between adverse childhood experiences (ACE), access to a medical home and a global measure of well-being among children ages 6-17 using the 2011-2012 National Survey of Children's Health. METHODS: Multivariate linear regressions assessed the associations between each adverse experience and an index of child well-being with and without the impact of other events. The number of ACE was summed for each respondent and the analyses were repeated with the cumulative score as a continuous variable. The cumulative model was repeated with the addition of an interaction term between ACE score and medical home access. All analyses were conducted separately for children ages 6 11 and adolescents 12-17. RESULTS: Over half (53 %) of US children ages 6-17 have experienced some adverse experience during childhood. Over a quarter (28 %) has experienced at least two adverse experiences, while 15 % have experienced three or more hardships. Results suggest that the accumulation of ACE reduces well being in children. The associations remained significant after controlling for gender, race/ethnicity, age, parental education, special health condition, and medical home access. Medical home access was consistently associated with higher levels of child well-being and was a significant moderator of the relationship between the total ACE and child well-being among children ages 6-11. Children with ACE exposure and access to a medical home have higher levels of well-being than comparable children without access to a medical home. CONCLUSIONS FOR PRACTICE: Children exposed to adverse experiences have measurably lower levels of well-being, although younger children with access to a medical home are protected at increasing exposure. PMID- 26140834 TI - Physical Activity and Sedentary Behavior Patterns Before and During Pregnancy in a Multi-ethnic Sample of Asian Women in Singapore. AB - OBJECTIVES: To describe physical activity (PA) and sedentary behavior (SB) patterns before and during pregnancy among Chinese, Malay and Indian women. In addition, to investigate determinants of change in PA and SB during pregnancy. METHODS: The Growing Up in Singapore Towards healthy Outcomes cohort recruited first trimester pregnant women. PA and SB (sitting time and television time) before and during pregnancy were assessed as a part of an interview questionnaire at weeks 26-28 gestational clinic visit. Total energy expenditure (TEE) on PA and time in SB were calculated. Determinants of change in PA and SB were investigated using multiple logistic regression analysis. RESULTS: PA and SB questions were answered by 94 % (n = 1171) of total recruited subjects. A significant reduction in TEE was observed from before to during pregnancy [median 1746.0-1039.5 metabolic equivalent task (MET) min/week, p < 0.001]. The proportion of women insufficiently active (<600 MET-min/week) increased from 19.0 to 34.1 % (p <0.001). Similarly, sitting time (median 56.0-63.0 h/week, p < 0.001) and television time (mean 16.1-16.7 h/week, p = 0.01) increased. Women with higher household income, lower level of perceived health, nausea/vomiting during pregnancy and higher level of pre-pregnancy PA were more likely to reduce PA. Women with children were less likely to reduce PA. Women reporting nausea/vomiting and lower level of pre-pregnancy sitting time were more likely to increase sitting time. CONCLUSIONS FOR PRACTICE: Participants substantially reduced PA and increased SB by 26-28 weeks of pregnancy. Further research is needed to better understand determinants of change in PA and SB and develop effective health promotion strategies. PMID- 26140835 TI - Labor and Delivery Experiences of Mothers with Suspected Large Babies. AB - OBJECTIVE: To characterize the prevalence of and factors associated with clinicians' prenatal suspicion of a large baby; and to determine whether communicating fetal size concerns to patients was associated with labor and delivery interventions and outcomes. METHODS: We examined data from women without a prior cesarean who responded to Listening to Mothers III, a nationally representative survey of women who had given birth between July 2011 and June 2012 (n = 1960). We estimated the effect of having a suspected large baby (SLB) on the odds of six labor and delivery outcomes. RESULTS: Nearly one-third (31.2%) of women were told by their maternity care providers that their babies might be getting "quite large"; however, only 9.9% delivered a baby weighing >=4000 g (19.7% among mothers with SLBs, 5.5% without). Women with SLBs had increased adjusted odds of medically-induced labor (AOR 1.9; 95% CI 1.4-2.6), attempted self-induced labor (AOR 1.9; 95% CI 1.4-2.7), and use of epidural analgesics (AOR 2.0; 95% CI 1.4-2.9). No differences were noted for overall cesarean rates, although women with SLBs were more likely to ask for (AOR 4.6; 95% CI 2.8-7.6) and have planned (AOR 1.8; 95% CI 1.0-4.5) cesarean deliveries. These associations were not affected by adjustment for gestational age and birthweight. CONCLUSIONS FOR PRACTICE: Only one in five US women who were told that their babies might be getting quite large actually delivered infants weighing >=4000 g. However, the suspicion of a large baby was associated with an increase in perinatal interventions, regardless of actual fetal size. PMID- 26140836 TI - Are Birth Certificate and Hospital Discharge Linkages Performed in 52 Jurisdictions in the United States? AB - OBJECTIVES: The purpose of this study was to determine the number and characteristics of US State Registrars of Vital Statistics (Vital Registrars) and State Systems Development Initiative (SSDI) Coordinators that link birth certificate and hospital discharge data as well as using linkage processes. METHODS: Vital Registrars and SSDI Coordinators in all 52 vital records jurisdictions (50 states, District of Columbia, and New York City) were asked to complete a 41-question survey. We examined frequency distributions among completed surveys using SAS 9.3. RESULTS: The response rate was 100% (N = 52) for Vital Registrars and 96% (N = 50) for SSDI Coordinators. Nearly half of Vital Registrars (n = 22) and SSDI Coordinators (n = 23) reported that their jurisdiction linked birth certificate and hospital discharge records at least once in the last 4 years. Among those who link, the majority of Vital Registrars (77.3%) and SSDI Coordinators (82.6) link both maternal and infant hospital discharge records to the birth certificate. Of those who do not link, 43% of the Vital Registrars and 55% of SSDI Coordinators reported an interest in linking birth certificate and hospital discharge data. Reasons for not linking included lack of staff time, inability to access raw data, high cost, and unavailability of personal identifiers to link the two sources. CONCLUSIONS: Results of our analysis provide a national perspective on data linkage practices in the US. Our findings can be used to promote further data linkages, facilitate sharing of data and linkage methodologies, and identify uses of the resulting linked data. PMID- 26140837 TI - Comparing Two Review Processes for Determination of Preventability of Maternal Mortality in Illinois. AB - OBJECTIVES: To compare the results of two maternal death review processes conducted from 2002 to 2012 by Illinois regionalized perinatal centers with those conducted by the Illinois Department of Public Health's (IDPH's) statewide multidisciplinary external Maternal Mortality Review Committee (MMRC). METHODS: This is a retrospective record review linking MMRC case assessment forms to the IDPH's Maternal Mortality Review Form database to compare causes of death and potential preventability as determined by both review processes. RESULTS: MMRC records for 76 maternal death reviews were linked to the IDPH maternal mortality review form database. Most deaths reviewed by the statewide MMRC were due to pregnancy-related causes. The statewide MMRC differed from the regional perinatal centers on cause of death in 55.3% (n = 42) of cases and on the disposition of potential preventability in 48.7% (n = 37) of cases. The statewide MMRC judged 69.7% (n = 53) of cases potentially preventable, compared with 40.8% (n = 31) for the regional perinatal centers. The MMRC identified more preventable provider and systems factors for potentially preventable deaths compared with regional perinatal centers which identified more preventable patient factors. CONCLUSIONS FOR PRACTICE: The statewide MMRC found more potential preventability and determined that preventability was associated with provider and systems factors, not patient factors. Observed discrepancies between regional perinatal center and statewide MMRC reviews were likely due to the complexity of cases selected for review, the multidisciplinary external composition of the review team, and the de identification of cases. Multidisciplinary statewide expert panels should be implemented in addition to local and regionalized reviews. PMID- 26140838 TI - Impact of ductal plate malformation on survival with native liver in children with biliary atresia. AB - PURPOSE: Ductal plate malformation (DPM) like arrays in the liver which resemble the characteristic persistent embryonal ductular structures have been shown to adversely affect the outcome of Kasai portoenterostomy (KPE) in biliary atresia (BA). We studied the impact of DPM on survival with native liver (SNL) in children with BA who underwent liver transplantation (LT) after KPE as well as those who underwent primary LT without KPE. METHODS: Records of children with BA who underwent LT in our institute were reviewed and divided into three groups Group 1 had primary LT because of delayed diagnosis of BA and synthetic liver failure, Group 2 had LT for synthetic liver failure after a failed KPE, and Group 3 had LT despite clearing jaundice after KPE for other indications. The impact of DPM on SNL was analyzed using standard statistical means. RESULTS: In Group 1 (n = 26) and Group 2 (n = 26), the incidence of DPM was high and was associated with a significantly shorter SNL compared to children with no DPM. The incidence of DPM was significantly lower in Group 3 (n = 13). CONCLUSION: DPM shortens SNL and influences the pathogenesis of disease progression in children with BA who had synthetic liver failure requiring transplantation either because of a failed KPE or due to a delay in diagnosis. Its incidence is low in children who cleared jaundice after KPE and needed transplantation for other indications at a later age. The presence of DPM signifies an adverse outcome for the disease. PMID- 26140839 TI - Appendicitis in children from a gender perspective. AB - BACKGROUND: The incidence in appendicitis and the appendectomy rate are different between boys and girls. This study aimed to further evaluate appendicitis in children from a gender perspective. Gender differences in presentation, perioperative care, and outcome after appendectomy were examined. METHOD: A single, institution-based, retrospective study was conducted at a tertiary pediatric surgery center. All children <15 years of age who underwent appendectomy for suspected appendicitis or who were conservatively treated for an appendiceal abscess, from 2006 to 2014, were included. Patient demographics, symptoms, preoperative management including time to appendectomy, operative characteristics, and postoperative course including complications and length of hospital stay were evaluated. RESULTS: The study included 427 children: 183 girls and 244 boys. The median postoperative follow-up time was 40 (range 1-106) months. The genders did not differ significantly in age, mean weight, symptoms, laboratory results, time to appendectomy, postoperative complications, postoperative pain management, antibiotic treatment, and length of hospital stay. The frequencies of hopping/percussion/coughing tenderness in the right lower quadrant (61 and 51%, p = 0.042), phlegmonous appendicitis (56 and 45%, p = 0.032), perforated appendicitis (18 and 10%, p = 0.043), and open appendectomy (57 and 28%, p = 0.048) were significantly higher in boys. Girls had significantly higher frequencies of preoperative imaging (50 and 38%, p = 0.021), negative appendectomy (18 and 7%, p = 0.005), gangrenous appendicitis (18 and 11%, p = 0.049), and operative complications (7 and 2%, p = 0.015). In girls, the Pediatric Appendicitis Score (PAS) was more specific (59 and 41%, respectively, p = 0.032) and had a greater negative predictive value (33 and 11%, respectively, p = 0.003) than in boys. CONCLUSION: In children with appendicitis, there are some gender differences. Girls had negative appendectomies more often, despite having more preoperative imaging and they had operative complications more frequently, despite having less frequent perforations. Boys had a higher frequency of perforation even though their time to appendectomy equaled that of girls. These findings and the reasons behind them must be further studied. PMID- 26140840 TI - Tityus bahiensis scorpion venom injected to dams during pregnancy affects some cytokines of fetuses. AB - Due to the high incidence of scorpion stings in Brazil, pregnant women are among the possible victims. Cytokines are important during the pregnancy, and scorpion venoms can change their release. We evaluated the levels of some cytokines in the fetuses after the treatment of pregnant rats with the Tityus bahiensis scorpion venom. The concentration of some of them is altered and can be responsible for the effects previously observed on innate reflexes, and the physical and behavioral development of the offspring. PMID- 26140841 TI - Key protection factors against tetanus: Anti-tetanus toxin antibody affinity and its ability to prevent tetanus toxin - ganglioside interaction. AB - Antibodies capable to neutralize tetanus toxin (TeNT) are key factors in protection against tetanus disease. Although antibody-based therapeutics for treatment of tetanus exist on the market its production is tedious. Hence, the tetanus-specific antibodies preparation that could be easily produced in large scale in vitro would be beneficial. Monoclonal antibodies (MAbs) are considered for a long time as a reagent of choice, but the core drawback is how to select a MAb that would be safe in providing efficacious protection. In this study we have investigated the parameters crucial for a single MAb to be assigned as protective. Eight murine MAbs were characterized in vitro for their reactivity toward TeNT and assessed in vivo for protectiveness against TeNT intoxication. Correlation of in vitro and in vivo data has revealed that in vitro selection of MAb that is protective in vivo could be performed by a combination of two assays: the measurement of MAb affinity toward TeNT taking Ka 1 * 10(8) M(-1) as a threshold level, and the evaluation of its capability to prevent TeNT-ganglioside interaction. Single MAb could be taken into consideration as a potential therapeutic only if it has a capacity to completely inhibits TeNT-ganglioside complex formation. PMID- 26140842 TI - Serological, biochemical and enzymatic alterations in rodents after experimental envenomation with Hadruroides lunatus scorpion venom. AB - Toxic effects of Peruvian Hadruroides lunatus scorpion venom on different biochemical and enzymatic parameters in blood serum of Wistar rats and Swiss mice were determined after experimental envenomation. An increase in enzymatic activities of Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and levels of serum protein and albumin were observed while a decrease in creatinine level in serum was perceived after 30 min of envenomation. No alterations in urea levels and in kidney histology were detected in the envenomed rats. The global leukocytes count was diminished, with decrease in lymphocytes, eosinophils and neutrophils levels in the bloodstream, while no alterations were found in hematological parameters of red series in rats injected with H. lunatus venom. IL 2, IL-4, IL-6, INF-gamma, TNF, IL-17A and IL-10 levels were evaluated 0.5, 3 and 6 h after experimental envenomation of mice with H. lunatus venom. From all the analyzed cytokines, only IL-6 showed an increase in serum levels. Taken together, these results point out that envenomation by H. lunatus can impair hematological and immunological parameters and therefore might be monitored in accidents involving this species. PMID- 26140843 TI - Leading Voices and the Power of One: 2002 Presidential Address to the National Society of Genetic Counselors. AB - Presented as the annual education conference of the National Society of Genetic Counselors in Phoenix, Arizona on November 11, 2002. PMID- 26140844 TI - Development of an Interactive Decision Aid for Female BRCA1/BRCA2 Carriers. AB - Shared decision making between patients and providers is becoming increasingly common, particularly when there is no clear preferred course of action. As a result, decision aids are being adopted with growing frequency and have been applied to many medical decision-making issues. One such issue where there is uncertainty is breast cancer risk management among BRCA1/BRCA2 carriers. We present the development of a CD-ROM decision aid to facilitate risk management decision making in this population. Our decision aid was developed with the intention of providing it through a randomized clinical trial. The CD-ROM is a multimedia, interactive intervention which provides information about breast cancer, risks associated with BRCA1 and BRCA2 mutations, risk management options for hereditary breast cancer, and a breast cancer risk management decision aid. The goal of this CD-ROM, offered as an adjunctive intervention, is to reduce decisional conflict and psychological distress and improve comprehension of risk information, decisional satisfaction, medical adherence, and quality of life for this population of women at increased risk for breast cancer. PMID- 26140845 TI - The Impact of Test Outcome Certainty on Interest in Genetic Testing Among College Women. AB - Osteoporosis and hemochromatosis are both late-onset preventable diseases, but future genetic tests for these conditions are likely to differ in their predictive abilities. To determine whether interest in a specific genetic test for hemochromatosis would be higher than interest in a theoretical test for osteoporosis susceptibility, undergraduate women at the University of Cincinnati (N = 181) were surveyed regarding their interest in genetic testing for these conditions. The clinical features of the diseases and the limits of a genetic test for each were described. Sixty-three percent of the total population was interested in genetic testing with a trend toward higher interest in the osteoporosis group. Disease familiarity, perceived disease severity, and perceived risk for disease appear to be more important predictors of genetic test acceptance than diagnostic specificity. Suggested implications for the development of population genetic screening tests are discussed. PMID- 26140846 TI - A Prospective Comparison Study of Different Methods of Gathering Self-Reported Family History Information for Breast Cancer Risk Assessment. AB - Currently there is much debate regarding the ability of mathematical models incorporating epidemiological information or mutation-based risk algorithms to accurately predict a woman's risk of developing breast cancer. Without access to accurate family history information these models have limited use. This study compares different methods of gathering family history information and the impact on subsequent risk assessment. These methods were compared to the "gold standard" interview with a trained genetics' professional. The amount and accuracy of information provided by primary care doctors' letters was found to be poor and better information was obtained by sending a postal questionnaire directly to the patient. Because of the high number of low-risk women referred to clinic a questionnaire (the FCAT) was designed to provide reassurance and piloted as part of this study. This paper highlights the importance of using appropriate methods to gather the family history information. It presents evidence for the importance of a skilled assessor and the need to allow time for women to discuss the importance of this information with their family. PMID- 26140847 TI - Assessment of the Effectiveness of Genetic Counseling by Telephone Compared to a Clinic Visit. AB - Maternal serum screening, also known as the triple screen, is used during pregnancy to assess the risk of carrying a fetus with specific chromosome abnormalities or open spina bifida. All women in British Columbia who screen positive are eligible for genetic counseling and are offered amniocentesis. The purpose of this study is to determine what differences (if any) exist in patients' understanding and/or anxiety when genetic counseling for a positive triple screen is conducted in person versus over the telephone. Each patient who participated was given the choice of having genetic counseling in person or over the telephone, this after a randomized design failed to elicit any participants. Using a written postcounseling questionnaire, each patient was assessed for her understanding of the information presented in the session, and her anxiety regarding her risk. In this small pilot study, no large differences were detected in patients' understanding or anxiety when genetic counseling was conducted by telephone versus in person. PMID- 26140848 TI - Genetic Library Video Reviews: Cancer Genetics. PMID- 26140849 TI - Do clinical, histological or immunohistochemical primary tumour characteristics translate into different (18)F-FDG PET/CT volumetric and heterogeneity features in stage II/III breast cancer? AB - PURPOSE: The aim of this retrospective study was to determine if some features of baseline (18)F-FDG PET images, including volume and heterogeneity, reflect clinical, histological or immunohistochemical characteristics in patients with stage II or III breast cancer (BC). METHODS: Included in the present retrospective analysis were 171 prospectively recruited patients with stage II/III BC treated consecutively at Saint-Louis hospital. Primary tumour volumes were semiautomatically delineated on pretreatment (18)F-FDG PET images. The parameters extracted included SUVmax, SUVmean, metabolically active tumour volume (MATV), total lesion glycolysis (TLG) and heterogeneity quantified using the area under the curve of the cumulative histogram and textural features. Associations between clinical/histopathological characteristics and (18)F-FDG PET features were assessed using one-way analysis of variance. Areas under the ROC curves (AUC) were used to quantify the discriminative power of the features significantly associated with clinical/histopathological characteristics. RESULTS: T3 tumours (>5 cm) exhibited higher textural heterogeneity in (18)F-FDG uptake than T2 tumours (AUC <0.75), whereas there were no significant differences in SUVmax and SUVmean. Invasive ductal carcinoma showed higher SUVmax values than invasive lobular carcinoma (p = 0.008) but MATV, TLG and textural features were not discriminative. Grade 3 tumours had higher FDG uptake (AUC 0.779 for SUVmax and 0.694 for TLG), and exhibited slightly higher regional heterogeneity (AUC 0.624). Hormone receptor-negative tumours had higher SUV values than oestrogen receptor-positive (ER-positive) and progesterone receptor-positive tumours, while heterogeneity patterns showed only low-level variation according to hormone receptor expression. HER-2 status was not associated with any of the image features. Finally, SUVmax, SUVmean and TLG significantly differed among the three phenotype subgroups (HER2-positive, triple-negative and ER-positive/HER2-negative BCs), but MATV and heterogeneity metrics were not discriminative. CONCLUSION: SUV parameters, MATV and textural features showed limited correlations with clinical and histopathological features. The three main BC subgroups differed in terms of SUVs and TLG but not in terms of MATV and heterogeneity. None of the PET-derived metrics offered high discriminative power. PMID- 26140851 TI - Clinically orientated classification incorporating shoulder balance for the surgical treatment of adolescent idiopathic scoliosis. AB - PURPOSE: The achievement of shoulder balance is an important measure of successful scoliosis surgery. No previously described classification system has taken shoulder balance into account. We propose a simple classification system for AIS based on two components which include the curve type and shoulder level. METHODS: Altogether, three curve types have been defined according to the size and location of the curves, each curve pattern is subdivided into type A or B depending on the shoulder level. This classification was tested for interobserver reproducibility and intraobserver reliability. A retrospective analysis of the radiographs of 232 consecutive cases of AIS patients treated surgically between 2005 and 2009 was also performed. RESULTS: Three major types and six subtypes were identified. Type I accounted for 30 %, type II 28 % and type III 42 %. The retrospective analysis showed three patients developed a decompensation that required extension of the fusion. One case developed worsening of shoulder balance requiring further surgery. This classification was tested for interobserver and intraobserver reliability. The mean kappa coefficients for interobserver reproducibility ranged from 0.89 to 0.952, while the mean kappa value for intraobserver reliability was 0.964 indicating a good-to-excellent reliability. CONCLUSIONS: The treatment algorithm guides the spinal surgeon to achieve optimal curve correction and postoperative shoulder balance whilst fusing the smallest number of spinal segments. The high interobserver reproducibility and intraobserver reliability makes it an invaluable tool to describe scoliosis curves in everyday clinical practice. PMID- 26140850 TI - FDG-PET/CT findings in systemic mastocytosis: a French multicentre study. AB - INTRODUCTION: Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG PET/CT (FDG-PET) in mastocytosis has yet to be determined. METHODS: We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data. RESULTS: Our cohort included 19 adult patients, median age 65 years [range 58 74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47%), LN (6/19, 32%), spleen (12/19, 63%), or liver (1/19, 5%). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells. CONCLUSIONS: FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients. PMID- 26140852 TI - Evidence for TiO2 nanoparticle transfer in a hard-rock aquifer. AB - Water flow and TiO2 nanoparticle (NP) transfer in a fractured hard-rock aquifer were studied in a tracer test experiment at a pilot site in Brittany, France. Results from the Br tracer test show that the schist aquifer can be represented by a two-layer medium comprising i) fractures with low longitudinal dispersivity in which water and solute transport is relatively fast, and ii) a network of small fissures with high longitudinal dispersivity in which transport is slower. Although a large amount of NPs was retained within the aquifer, a significant TiO2 concentration was measured in a well 15m downstream of the NP injection well, clearly confirming the potential for TiO2 NPs to be transported in groundwater. The Ti concentration profile in the downstream well was modelled using a two-layer medium approach. The delay used for the TiO2 NPs simulation compared to the Br concentration profiles in the downstream well indicate that the aggregated TiO2 NPs interacted with the rock. Unlike Br, NPs do not penetrate the entire pore network during transfer because of electrostatic interactions between NP aggregates and the rock and also to the aggregate size and the hydrodynamic conditions, especially where the porosity is very low; NPs with a weak negative charge can be attached onto the rock surface, and more particularly onto the positively charged iron oxyhydroxides coating the main pathways due to natural denitrification. Nevertheless, TiO2 NPs are mobile and transfer within fracture and fissure media. Any modification of the aquifer's chemical conditions is likely to impact the groundwater pH and, the nitrate content and the denitrification process, and thus affect NP aggregation and attachment. PMID- 26140853 TI - The influence of biofilms on the mobility of bare and capped zinc oxide nanoparticles in saturated sand and glass beads. AB - Biofilms are a common constituent of the subsurface and are known to influence contaminant transport; however only a few studies to date have addressed microbial controls on nanoparticle mobility in porous media. The impact of a 3 day Pantoea agglomerans biofilm on the mobility of zinc oxide (ZnO) nanoparticles was studied in column experiments containing sand and glass beads at near-neutral pH and constant ionic strength. Bare ZnO nanoparticles (bZnO-NPs) and ZnO nanoparticles capped with tri-aminopropyltriethoxysilane (cZnO-NPs) were used in the experiments. Breakthrough curves demonstrate that the biofilm particularly slowed nanoparticle migration of bZnO-NPs in glass bead columns and cZnO-NPs in sand columns. With the exception of bZnO-NPs in sand columns, biofilm-coated porous media retained more nanoparticles than those of controls without biofilm. The biofilm may bear an impact on the surface charge of the porous medium, nullifying porous medium-specific effects. Although viable cell counts (VCCs) decreased after the introduction of electrolyte and before nanoparticle transport experiments, SEM and CLSM imaging of porous medium samples taken from columns after nanoparticle transport experiments, as well as total organic carbon (TOC) measurements reveal that biofilm was present in the columns throughout the experiments. Hence, it can be concluded that even a thin amount of biofilm can hinder nanoparticle migration in small-scale porous medium experiments. Moreover, nanoparticle mobility is dependent on the binding capacity of biofilms, rather than the type of porous media. PMID- 26140854 TI - Involvement of MeCP2 in Regulation of Myelin-Related Gene Expression in Cultured Rat Oligodendrocytes. AB - Methyl CpG binding protein 2 (MeCP2) is a multifunctional protein which binds to methylated CpG, mutation of which cause a neurodevelopmental disorder, Rett syndrome. MeCP2 can function as both transcriptional activator and repressor of target gene. MeCP2 regulate gene expression in both neuron and glial cells in central nervous system (CNS). Oligodendrocytes, the myelinating cells of CNS, are required for normal functioning of neurons and are regulated by several transcription factors during their differentiation. In current study, we focused on the role of MeCP2 as transcription regulator of myelin genes in cultured rat oligodendrocytes. We have observed expression of MeCP2 at all stages of oligodendrocyte development. MeCP2 knockdown in cultured oligodendrocytes by small interference RNA (siRNA) has shown increase in myelin genes (myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), and myelin-associated oligodendrocyte basic protein (MOBP)), neurotrophin (brain-derived neurotrophic factor (BDNF)), and transcriptional regulator (YY1) transcripts level, which are involved in regulation of oligodendrocyte differentiation and myelination. Further, we also found that protein levels of MBP, PLP, DM-20, and BDNF also significantly upregulated in MeCP2 knockdown oligodendrocytes. Our study suggests that the MeCP2 acts as a negative regulator of myelin protein expression. PMID- 26140855 TI - Reoperative Surgery for Management of Early Complications After Gastric Bypass. AB - INTRODUCTION: Most papers discussing specifics of reoperative surgery after laparoscopic Roux-en-Y gastric bypass (LRYGB) are over 10 years old. METHODS: A retrospective analysis of patients undergoing reoperative surgery within 30 days of LRYGB. RESULTS: Over a 5-year period, 52 out of 1769 (2.9%) patients underwent reoperation within 30 days of the index LRYGB. The 30-day reoperative surgery rate was 2.5% for primary and 7.1% for revisional LRYGB. The most common indications for reoperation included bleeding (n = 16), followed by bowel obstruction (n = 14), leak (n = 14), and diagnostic exploration for tachycardia and abdominal pain (n = 4). Forty-nine (94%) reoperations were started laparoscopically and six (12%) required conversion to laparotomy. The most common sources of bleeding were the mesenteric vessels (n = 6); the most common cause of obstruction was adhesion (n = 5), and the most common site of leak was the gastric pouch and gastrojejunal anastomosis (n = 9). Twenty (38%) patients developed further complications that led to a third surgery in nine (17%) patients. There were no significant differences as far cause for reoperation noted between patients undergoing primary surgery versus revisional surgery. The 90-day readmission and mortality rates were 29% and zero, respectively. CONCLUSION: Type of complications is comparable, and number of complications requiring early surgical reintervention following primary or revisional LRYGB is low. Increasing proportion of patients requiring early reoperation will have undergone a revisional surgery. The majority of these reoperations are accomplished laparoscopically. Bleeding continues to be the most common cause for early reoperation. Although associated with significant morbidity, mortality is rare in this patient population. PMID- 26140856 TI - The Effect of Route of Anvil Insertion on Stricture Rates with Circular Stapled Gastrojejunostomy During Laparoscopic Gastric Bypass. AB - BACKGROUND: A higher incidence of gastrojejunal (GJ) anastomotic strictures has been reported following laparoscopic gastric bypass (LRYGB) with the 21 mm compared to 25 mm circular stapler. We hypothesized that the rate of stricture formation is affected by route of anvil insertion and its position relative to the gastric pouch staple line [trans-gastric above staple line (trans-gastric) vs. trans-oral through staple line (trans-oral)] following LRYGB. METHODS: Retrospective review of consecutive patients who underwent LRYGB with circular stapled GJ studied in four groups: trans-gastric-21 mm, trans-gastric-25 mm, trans-oral-21 mm, and trans-oral-25 mm. Primary outcome studied was GJ stricture; secondary outcomes were results with endoscopic therapy and weight loss at 12 months. Predictors studied were age, gender, body mass index (BMI), comorbidities, and operative technical factors including anvil size and insertion route. Regression analyses were performed to identify predictors of GJ stricture. RESULTS: Eight hundred seventy-six patients underwent LRYGB. Seventy-six (8.7 %) developed a GJ stricture. The highest stricture rate occurred in the trans gastric-21 mm group (17 %, p < .01 for all comparisons). Stricture rates were similar for trans-gastric-25 mm (8.4 %), trans-oral-21 mm (5.2 %), and trans-oral 25 mm (1.6 %) groups. Independent predictors of stricture were: trans-gastric-21 mm (OR 10.9, 95%CI 1.4-85.1; p = .022) and age (OR 0.97, 95%CI 0.95-0.99; p = .002). Endoscopic dilation relieved symptoms in all patients. There was no difference in %EWL at 12 months in patients with and without a stricture. CONCLUSIONS: We conclude that the trans-oral-21 mm anvil is associated with a low stricture rate. With the advantage of smaller abdominal wall wound, trans-oral-21 mm may be the preferred size and route of anvil insertion. PMID- 26140857 TI - Comparing Israeli and Palestinian polio vaccination policies and the challenges of silent entry of wild poliovirus in 2013-14: a 'natural experiment'. PMID- 26140858 TI - Healthy living practices in families and child health in Taiwan. AB - OBJECTIVES: The aim of this study was to examine the hypothesis that inexpensive and feasible healthy living practices in families, particularly in disadvantaged families, can promote the health of children. METHODS: The dataset was obtained from the Taiwan Birth Cohort Study and comprises a nationally representative sample of 19,712 3-year-old children in Taiwan. The Child Healthy Living Practices in Families (CHLPF) Index, which rates various items of personal hygiene, vegetable and fruit consumption, physical activity, time spent viewing television, and exposure to smoking, was created, and a logistic regression analysis was conducted to test the hypothesis. RESULTS: Higher CHLPF levels were significantly and consistently associated with better child health in families of all income levels. More specifically, the prevalence of ill health in children from poor families with a high CHLPF level was actually lower than that in children from affluent families with a low CHLPF level. CONCLUSIONS: The implementation of low-cost and practical healthy living practices in families can effectively improve child health, especially that of disadvantaged children. PMID- 26140859 TI - After the epidemiologic transition: a reassessment of mortality from infectious diseases among over-65s in France and Italy. AB - OBJECTIVES: To assess more accurately the contribution of infectious diseases (IDs) to mortality at age 65+. METHODS: We use cause-of-death data for France and Italy in 2009. In addition to chapter I of the 10th International Classification of Diseases (ICD-10), our list of IDs includes numerous diseases classified in other chapters. We compute mortality rates considering all death certificate entries (underlying and contributing causes). RESULTS: Mortality rates at age 65+ based on our extended list are more than three times higher than rates based solely on ICD-10 chapter I. IDs are frequently contributing causes of death. In France, the share of deaths at age 65+ involving an ID as underlying cause increases from 2.1 to 7.3 % with the extended list, and to 20.8 % when contributing causes are also considered. For Italy, these percentages are 1.4, 4.2 and 18.7 %, respectively. CONCLUSIONS: Publicly available statistics underestimate the contribution of IDs to the over-65s' mortality. Old age is a risk factor for IDs, and these diseases are more difficult to treat at advanced ages. Health policies should develop targeted actions for that population. PMID- 26140860 TI - The mediating effect of daily nervousness and irritability on the relationship between soft drink consumption and aggressive behaviour among adolescents. AB - OBJECTIVES: This study investigated whether soft drink consumption is related to fighting and bullying behaviour among school-aged children and whether nervousness and irritation mediated this relationship. METHODS: The data on 7583 adolescents aged 11-15 years from the Slovak part of the Health Behaviour in School-Aged Children (HBSC) study 2010 were analysed. Self-reported soft drink intake, bullying, fighting, nervousness, irritability and confounding variables were analysed using logistic regressions. To assess the potential mediation of daily nervousness and irritability on the association between soft drink consumption and aggressive behaviour, we used Sobel tests. RESULTS: Adolescents' daily soft drink consumption was associated with bullying and fighting, and these relationships were partially mediated by nervousness and irritability. Adjustment of the analyses on gender, age and family affluence did not change the estimates. CONCLUSIONS: Adolescents' daily soft drink consumption was associated with negative mood deviations such as nervousness and irritability and with aggressive behaviour in the form of bullying and fighting. Our findings provide new evidence about soft drink consumption-related risks and thus can contribute to the preventive actions aimed at reducing them. PMID- 26140861 TI - A molecular genetic time scale demonstrates Cretaceous origins and multiple diversification rate shifts within the order Galliformes (Aves). AB - The phylogeny of Galliformes (landfowl) has been studied extensively; however, the associated chronologies have been criticized recently due to misplaced or misidentified fossil calibrations. As a consequence, it is unclear whether any crown-group lineages arose in the Cretaceous and survived the Cretaceous Paleogene (K-Pg; 65.5 Ma) mass extinction. Using Bayesian phylogenetic inference on an alignment spanning 14,539 bp of mitochondrial and nuclear DNA sequence data, four fossil calibrations, and a combination of uncorrelated lognormally distributed relaxed-clock and strict-clock models, we inferred a time-calibrated molecular phylogeny for 225 of the 291 extant Galliform taxa. These analyses suggest that crown Galliformes diversified in the Cretaceous and that three-stem lineages survived the K-Pg mass extinction. Ideally, characterizing the tempo and mode of diversification involves a taxonomically complete phylogenetic hypothesis. We used simple constraint structures to incorporate 66 data-deficient taxa and inferred the first taxon-complete phylogenetic hypothesis for the Galliformes. Diversification analyses conducted on 10,000 timetrees sampled from the posterior distribution of candidate trees show that the evolutionary history of the Galliformes is best explained by a rate-shift model including 1-3 clade specific increases in diversification rate. We further show that the tempo and mode of diversification in the Galliformes conforms to a three-pulse model, with three-stem lineages arising in the Cretaceous and inter and intrafamilial diversification occurring after the K-Pg mass extinction, in the Paleocene-Eocene (65.5-33.9 Ma) or in association with the Eocene-Oligocene transition (33.9 Ma). PMID- 26140862 TI - Gene duplication, loss and selection in the evolution of saxitoxin biosynthesis in alveolates. AB - A group of marine dinoflagellates (Alveolata, Eukaryota), consisting of ~10 species of the genus Alexandrium, Gymnodinium catenatum and Pyrodinium bahamense, produce the toxin saxitoxin and its analogues (STX), which can accumulate in shellfish, leading to ecosystem and human health impacts. The genes, sxt, putatively involved in STX biosynthesis, have recently been identified, however, the evolution of these genes within dinoflagellates is not clear. There are two reasons for this: uncertainty over the phylogeny of dinoflagellates; and that the sxt genes of many species of Alexandrium and other dinoflagellate genera are not known. Here, we determined the phylogeny of STX-producing and other dinoflagellates based on a concatenated eight-gene alignment. We determined the presence, diversity and phylogeny of sxtA, domains A1 and A4 and sxtG in 52 strains of Alexandrium, and a further 43 species of dinoflagellates and thirteen other alveolates. We confirmed the presence and high sequence conservation of sxtA, domain A4, in 40 strains (35 Alexandrium, 1 Pyrodinium, 4 Gymnodinium) of 8 species of STX-producing dinoflagellates, and absence from non-producing species. We found three paralogs of sxtA, domain A1, and a widespread distribution of sxtA1 in non-STX producing dinoflagellates, indicating duplication events in the evolution of this gene. One paralog, clade 2, of sxtA1 may be particularly related to STX biosynthesis. Similarly, sxtG appears to be generally restricted to STX-producing species, while three amidinotransferase gene paralogs were found in dinoflagellates. We investigated the role of positive (diversifying) selection following duplication in sxtA1 and sxtG, and found negative selection in clades of sxtG and sxtA1, clade 2, suggesting they were functionally constrained. Significant episodic diversifying selection was found in some strains in clade 3 of sxtA1, a clade that may not be involved in STX biosynthesis, indicating pressure for diversification of function. PMID- 26140863 TI - Sleep medicine in ayurveda. PMID- 26140864 TI - Are cognitive "insomnia" processes involved in the development and maintenance of delayed sleep wake phase disorder? AB - Although individuals with delayed sleep wake phase disorder (DSWPD) and chronic insomnia disorder (CID) share many of the same phenomenological experiences, theories relating to the development and maintenance of these disorders are distinct in focus. Unlike CID, theory relating to DSWPD is primarily physiologically based and assumes almost no cognitive pathway. However, recent research findings suggest that individuals with DSWPD also display many of the sleep-disordered cognitive processes that were previously assumed to be unique to the insomnia experience. As such, this review aims to summarise current research findings to address the question "Could cognitive processes be involved in the development and maintenance of DSWPD?" In particular, the presence of cognitive and physiological pre-sleep arousal, sleep-related attentional bias, distorted perception of sleep and daytime functioning, dysfunctional beliefs and safety behaviours will be investigated. As this emerging area of research requires a stronger evidence base, we highlight suggestions for future investigation and provide preliminary practice points for clinicians assessing and treating "insomnia" in patients with DSWPD. PMID- 26140865 TI - Effects of intrauterine growth restriction on sleep and the cardiovascular system: The use of melatonin as a potential therapy? AB - Intrauterine growth restriction (IUGR) complicates 5-10% of pregnancies and is associated with increased risk of preterm birth, mortality and neurodevelopmental delay. The development of sleep and cardiovascular control are closely coupled and IUGR is known to alter this development. In the long-term, IUGR is associated with altered sleep and an increased risk of hypertension in adulthood. Melatonin plays an important role in the sleep-wake cycle. Experimental animal studies have shown that melatonin therapy has neuroprotective and cardioprotective effects in the IUGR fetus. Consequently, clinical trials are currently underway to assess the short and long term effects of antenatal melatonin therapy in IUGR pregnancies. Given melatonin's role in sleep regulation, this hormone could affect the developing infants' sleep-wake cycle and cardiovascular function after birth. In this review, we will 1) examine the role of melatonin as a therapy for IUGR pregnancies and the potential implications on sleep and the cardiovascular system; 2) examine the development of sleep-wake cycle in fetal and neonatal life; 3) discuss the development of cardiovascular control during sleep; 4) discuss the effect of IUGR on sleep and the cardiovascular system and 5) discuss the future implications of melatonin therapy in IUGR pregnancies. PMID- 26140868 TI - Desperately seeking grey matter volume changes in sleep apnea: A methodological review of magnetic resonance brain voxel-based morphometry studies. AB - Cognitive impairment related to obstructive sleep apnea might be explained by subtle changes in brain anatomy. This has been mainly investigated using magnetic resonance brain scans coupled with a voxel-based morphometry analysis. However, this approach is prone to several methodological pitfalls that may explain the large discrepancy in the results reported in the literature. We critically reviewed twelve papers addressing grey matter volume modifications in association with obstructive sleep apnea. Finally, based on strict methodological criteria, only three studies reported robust, but conflicting, results. No clear evidence has emerged and exploring brain alteration due to obstructive sleep apnea should thus be considered as an open field. We provide recommendations for designing additional robust voxel-based morphometry studies, notably the use of larger cohorts, which is the only way to solve the underpowered issue and the underestimated role of confounders in neuroimaging studies. PMID- 26140867 TI - Risk factors for sleep disturbances in older adults: Evidence from prospective studies. AB - No systematic review of epidemiological evidence has examined risk factors for sleep disturbances among older adults. We searched the PubMed database combining search terms targeting the following domains 1) prospective, 2) sleep, and 3) aging, and identified 21 relevant population-based studies with prospective sleep outcome data. Only two studies utilized objective measures of sleep disturbance, while six used the Pittsburgh sleep quality index (PSQI) and thirteen used insomnia symptoms or other sleep complaints as the outcome measure. Female gender, depressed mood, and physical illness were most consistently identified as risks for future sleep disturbances. Less robust evidence implicated the following as potentially relevant predictors: lower physical activity levels, African-American race, lower economic status, previous manual occupation, widowhood, marital quality, loneliness and perceived stress, preclinical dementia, long-term benzodiazepine and sedative use, low testosterone levels, and inflammatory markers. Chronological age was not identified as a consistent, independent predictor of future sleep disturbances. In conclusion, prospective studies have identified female gender, depressed mood, and physical illness as general risk factors for future sleep disturbances in later life, although specific physiological pathways have not yet been established. Research is needed to determine the precise mechanisms through which these factors influence sleep over time. PMID- 26140866 TI - Polysomnographic characteristics in nonmalignant chronic pain populations: A review of controlled studies. AB - Sleep and pain are critical homeostatic systems that interact in a bidirectional manner. Complaints of sleep disturbance are ubiquitous among patients with chronic pain disorders, and conversely, patients with persistent insomnia symptoms commonly report suffering from chronic pain. Sleep deprivation paradigms demonstrate that partial or complete sleep loss induce hyperalgesia, possibly due to shared mechanistic pathways including neuroanatomic and molecular substrates. Further, chronic pain conditions and sleep disturbances are intertwined through comorbidities, which together cause detrimental psychological and physical consequences. This critical review examines 29 polysomnography studies to evaluate whether nonmalignant chronic pain patients, as compared to controls, show differences in objective measures of sleep continuity and sleep architecture. Whereas these controlled studies did not reveal a consistent pattern of objective sleep disturbances, alterations of sleep continuity were commonly reported. Alterations of sleep architecture such as increases in light sleep or decreases in slow-wave sleep were less commonly reported and findings were mixed and also inconsistent. Methodological flaws were identified, which complicated interpretation and limited conclusions; hence, recommendations for future research are suggested. Knowledge of abnormalities in the sleep process has implications for understanding the pathophysiology of chronic pain conditions, which might also direct the development of novel intervention strategies. PMID- 26140869 TI - The relation between peer victimization and sleeping problems: A meta-analysis. AB - Peer victimization has been found related to sleeping problems in children and adolescents in multiple studies. The aim of the current meta-analysis is to study the relation between peer victimization and sleeping problems. The databases PsycINFO, MEDLINE, ERIC, Embase and LILACS were searched for articles. There were 21 articles that met the criteria for inclusion in the meta-analysis. These 21 articles contained 46 independent effect sizes and 363,539 children and adolescents, ranging in age from 7 up to 19 y of age. Results revealed that peer victimization is related to more sleeping problems. These results were not affected by publication bias. Moderator analyses revealed that for younger children the relation between peer victimization and sleeping problems was stronger than for older children. Results suggest that sleeping problems may be used as a possible signal that a child is victimized by peers. PMID- 26140870 TI - Trauma-induced insomnia: A novel model for trauma and sleep research. AB - Traumatic events have been increasingly recognized as important precipitants of clinically significant insomnia. Trauma is an extreme form of stressful life event that generates a sustained neurobiological response triggering the onset and maintenance of insomnia. Trauma may disrupt the normal sleep-wake regulatory mechanism by sensitizing the central nervous system's arousal centers, leading to pronounced central and physiological hyperarousal. The central concept of hyperarousal has been linked to both the pathogenesis of insomnia and to the neurobiological changes in the aftermath of traumatic events, and may be a neurobiological commonality underlying trauma and insomnia. This paper presents evidence for trauma-induced insomnia and advances a model of it as an important nosological and neurobiological entity. Trauma-induced insomnia may occur in the absence of full-blown posttraumatic stress disorder (PTSD), and may also be a precursor of subsequent PTSD development. Converging lines of evidence from the neuroscience of insomnia with the neurobiology and psychophysiology of stress, fear, trauma and PTSD will be integrated to advance understanding of the condition. Preclinical and clinical stress and fear paradigms have informed the neurobiological pathways mediating the production of insomnia by trauma. Elucidating the underlying neurobiological substrates can establish novel biological markers to identify persons at risk for the condition, and help optimize treatment of the trauma-insomnia interface. Early identification and treatment of trauma-induced insomnia may prevent the development of PTSD, as well as other important sequelae such as depression, substance dependence, and other medical conditions. PMID- 26140871 TI - Sleepiness, attention and risk of accidents in powered two-wheelers. AB - In recent years, the role of "sleepiness at the wheel" in the occurrence of accidents has been increasingly highlighted with several national and international public health campaigns based on consensual research publications. However, one aspect of this phenomenon is rarely taken into account, i.e., the risk of sleep-induced accidents while riding powered two-wheelers (PTWs). PTWs are indeed involved in a high percentage of fatal accidents mostly with young male riders. The effects of sleepiness may be different in drivers and riders, partly because riders may be stimulated more by the road environment. But riders (differently from drivers) have also to maintain continuously a balance between their own stability and the need of following the road, even when they are directly exposed to adverse climatic conditions. We, therefore, gathered the limited scientific literature on this topic and tried to analyze how riders may be affected differently by sleepiness. Finally we provide some suggestions as to how this question may be better approached in the future. PMID- 26140872 TI - Bariatric Complications for the Acute Care Surgeon: Perforated Marginal Ulcer After a Roux-en-Y Gastric Bypass. PMID- 26140873 TI - Surgeon-Performed Duplex Ultrasound Facilitates Diagnosis and Management of Blunt Popliteal Artery Injury. PMID- 26140874 TI - An Optimized Preparation Technique for Saphenous Vein Graft. PMID- 26140875 TI - Economic Impact of Laparoscopic Appendectomy in a Rural Hospital. PMID- 26140876 TI - Chronic Expanding Hematoma of the Thigh Masquerading as a Soft Tissue Malignancy. PMID- 26140877 TI - Jet Ski Hydrostatic Perineal Injuries from a Level I Trauma Experience. PMID- 26140878 TI - Analysis of Patients Undergoing Coronary Artery Bypass Grafting Who Have Already Had Prior Percutaneous Coronary Intervention. PMID- 26140879 TI - Isolated Celiac Artery Dissection in Blunt Abdominal Trauma. PMID- 26140880 TI - Biliary Duplication Cyst. PMID- 26140881 TI - Indeterminate Thyroid Nodule: Knowing What We Do Not Know. PMID- 26140882 TI - Journalism and Academic Surgery: The Denver Post and The American Surgeon. AB - Publication in professional journals is where advancements in surgery are reported and verified. Thus academic surgery holds common ground with journalism, where the principles of service, communication, and integrity are the basis of their public trust and standing in society. Writing for the Denver Post the author learned lessons that are relevant to academic surgery. Facts have to be solid. There are important issues to be discussed. Articles have to be interesting and not tiresome to read. And if it's something new--the essence of news--get it out there first. The American Surgeon embodies the same principles. The journal is a place where members of the Southeastern Surgical Congress discuss important matters, like surgical education, and share stories of interest, like a Japanese surgeon trying to treat victims of nuclear war. It is accessible yet disciplined, dedicated to advancing our field and fostering fellowship and communication among its members. PMID- 26140883 TI - Electromagnetic Navigational Bronchoscopy: A Safe and Effective Method for Fiducial Marker Placement in Lung Cancer Patients. AB - The emergence of Electromagnetic Navigational Bronchoscopy (ENB) as a diagnostic tool for small peripheral lung nodules has introduced a new method for delivery of fiducial markers. This technique has not been well studied in the literature. The purpose of our study was to evaluate the safety and effectiveness of ENB when used in fiducial marker placement. We reviewed all patients undergoing ENB fiducial placement between June 2010 and February 2014 (n = 64). These 64 patients had 68 lung lesions, in which we placed a total of 190 markers. Primary end points were marker retention and postoperative complications. The retention rate for the study was 82 per cent (n = 156). Upper lobe lesions had a 78 per cent retention rate and the middle/lower lobe lesions had an 89 per cent retention rate; the difference was not significant (P = 0.126). Complications included hospital admissions, respiratory failure, and pneumothorax. The difference in complication rates between upper and middle/lower lobe markers was not significant. We found ENB to be a safe method for the placement of fiducial markers. We also found that placement of an average of three markers/lesion led to an adequate retention rate to allow for successful treatment of lung cancer in nonsurgical patients using lung-sparing stereotactic radiation. PMID- 26140884 TI - Coagulation Profile Changes Due to Thromboprophylaxis and Platelets in Trauma Patients at High-Risk for Venous Thromboembolism. AB - We hypothesize there are coagulation profile changes associated both with initiation of thromboporphylaxis (TPX) and with change in platelet levels in trauma patients at high-risk for venous thromboembolism (VTE). A total of 1203 trauma intensive care unit patients were screened with a VTE risk assessment profile. In all, 302 high-risk patients (risk assessment profile score >= 10) were consented for weekly thromboelastography. TPX was initiated between initial and follow-up thromboelastography. Seventy-four patients were analyzed. Upon admission, 87 per cent were hypercoagulable, and 81 per cent remained hypercoagulable by Day 7 (P = 0.504). TPX was initiated 3.4 +/- 1.4 days after admission; 68 per cent received unfractionated heparin and 32 per cent received low-molecular-weight heparin. The VTE rate was 18 per cent, length of stay 38 (25 37) days, and mortality of 17.6 per cent. In all, 76 per cent had a rapid clotting time at admission versus 39 per cent at Day 7 (P < 0.001); correcting from 7.75 (6.45-8.90) minutes to 10.45 (7.90-15.25) minutes (P < 0.001). At admission, 41 per cent had an elevated maximum clot formation (MCF) and 85 per cent had at Day 7 (P < 0.001); increasing from 61(55-65) mm to 75(69-80) mm (P < 0.001). Platelets positively correlated with MCF at admission (r = 0.308, R(2) = 0.095, P = 0.008) and at Day 7 (r = 0.516, R(2) = 0.266, P < 0.001). Change in platelet levels correlated with change in MCF (r = 0.332, R(2) = 0.110, P = 0.005). In conclusion, hypercoagulability persists despite the use of TPX. Although clotting time normalizes, MCF increases in correlation with platelet levels. As platelet function is a dominant contributor to sustained trauma-evoked hypercoagulability, antiplatelet therapy may be indicated in the management of severely injured trauma patients. PMID- 26140885 TI - HIDA Scan with Ejection Fraction Is over Utilized in the Management of Biliary Dyskinesia. AB - Patients with upper abdominal pain, nausea, and vomiting are often evaluated with ultrasound to diagnose symptomatic cholelithiasis or cholecystitis. With a normal ultrasound, a hepatobiliary iminodiacetic acid (HIDA) scan with ejection fraction (EF) is recommended to evaluate gallbladder function. The purpose of this study was to evaluate whether the HIDA scan with EF was appropriately utilized in considering cholecystectomy. Over 18 months, we performed 1533 HIDA scans with EF. After exclusion, 1501 were analyzable, 438 of whom underwent laparoscopic cholecystectomy. Patients were divided into two groups: those with typical and atypical symptoms of biliary colic. Our primary endpoint was symptom resolution of those who underwent laparoscopic cholecystectomy. Symptom resolution was assessed by chart review of postop visits or readmissions. In patients with typical symptoms, resolution occurred in 66 per cent of patients with positive HIDA and 77 per cent with negative HIDA (P = 0.292). In patients with atypical symptoms, resolution occurred in 64 per cent of patients with positive HIDA and 43 per cent with negative HIDA (P = 0.013). A HIDA scan with EF was not useful in patients with typical symptoms of biliary colic and negative ultrasounds, and should not be used to make a decision for cholecystectomy. However, this test can be helpful in patients with atypical symptoms, as it does predict symptom improvement in this group. PMID- 26140886 TI - Synergistic Effect of Combined Hollow Viscus Injuries on Intra-Abdominal Abscess Formation. AB - The strong association between penetrating colon injuries and intra-abdominal abscess (IAA) formation is well established and attributed to high colon bacterial counts. Since trauma patients are rarely fasting at injury, stomach and small bowel colony counts are also elevated. We hypothesized that there is a synergistic effect of increased IAA formation with concomitant stomach and/or colon injuries when compared to small bowel injuries alone. Consecutive patients at a level one trauma center with penetrating small bowel (SB), stomach (S), and/or colon (C) injuries from 1996 to 2012 were reviewed. Logistic regression determined associations with IAA, adjusting for age, gender, Injury Severity Score (ISS), admission Glasgow Coma Score, transfusions, and concurrent pancreas or liver injury. A total of 1518 patients (91% male, ISS = 15.9 +/- 8.4) were identified: 496 (33%) SB, 231 (15%) S, 288 (19%) C, 40 (3%) S + SB, 69 (5%) S + C, 338 (22%) C + SB, and 56 (4%) S + C + SB. 148 (10%) patients developed IAA: 4 per cent SB, 9 per cent S, 10 per cent C, 5 per cent S + SB, 22 per cent S + C, 13 per cent C + SB, and 25 per cent S + C + SB. Multiple logistic regression demonstrated that ISS, 24 hour blood transfusions, and concomitant pancreatic or liver injuries were associated with IAA. Compared with reference SB, S or S + SB injuries were no more likely to develop IAA. However, S + C, SB + C, and S + C + SB injuries were significantly more likely to have IAA. In conclusion, combined stomach + colon, small bowel + colon, and stomach, colon, + small bowel injuries have a synergistic effect leading to increased IAA formation after penetrating injuries. Heightened clinical suspicion for IAA formation is necessary in these combined hollow viscus injury patients. PMID- 26140887 TI - Incisional Hernia Classification Predicts Wound Complications Two Years after Repair. AB - Classification of ventral hernias (VHs) into categories that impact surgical outcome is not well defined. The European Hernia Society (EHS) classification divides ventral incisional hernias by midline or lateral location. This study aimed to determine whether EHS classification is associated with wound complications after VH repair, indicated by surgical site occurrences (SSOs). A retrospective cohort study of patients who underwent VH repair at a tertiary referral center between July 1, 2005 and May 30, 2012, was performed. EHS classification, comorbidities, and operative details were determined. Primary outcome was SSO within two years, defined as an infection, wound dehiscence, seroma, or enterocutaneous fistula. There were 538 patients included, and 51.5 per cent were female, with a mean age of 54.2 +/- 12.4 years and a mean body mass index of 32.4 +/- 8.6 kg/m(2). Most patients had midline hernias (87.0%, n = 468). There were 47 patients (8.7%) who had a lateral hernia, and 23 patients (4.3%) whose repair included both midline and lateral components. Overall rate of SSO was 39 per cent (n = 211) within two years. The rate of SSO by VH location was: 39 per cent (n = 183) for midline, 23 per cent (n = 11) for lateral, and 74 per cent (n = 17) for VHs with midline and lateral components (P = <0.001). Patients whose midline hernia spanned more than one EHS category also had a higher rate of SSOs (P = 0.001). VHs are often described by transverse dimension alone, but a more descriptive classification system offers a richness that correlates with outcomes. PMID- 26140888 TI - A Multidisciplinary Approach to Improving SCIP Compliance. AB - The Surgical Care Improvement Project (SCIP) is a national program aimed at reducing perioperative complications and is a quality benchmark metric for Centers for Medicare and Medicaid Services. This study evaluates whether a multidisciplinary program improved an institution's compliance with SCIP measures. Analysis of the facility's performance data identified three key areas of SCIP noncompliance: 1) timely discontinuation of perioperative antibiotics and urinary catheters, 2) initiation of venous thromboembolism prophylaxis, and 3) perioperative beta blocker administration. Multidisciplinary teams collaborated with providers and department chairs in reviewing and enable SCIP compliance. Anesthesia staff managed preoperative antibiotics. SCIP-compliant order sets, venous thromboembolism pop-up alerts, and progress note templates were added to the electronic medical record. Standardized education was provided to explain SCIP requirements, review noncompliant cases, and update teams on SCIP performance. Data were captured from January 2009 to March 2014. Ten SCIP fallouts were reported for general surgery specialties in January 2013, when the SCIP compliance project launched. Specifically, colon-related surgery achieved 100 per cent compliance. Six months after implementation, overall SCIP compliance at our institution improved by 65 per cent (from 90.7-98.6% compliance). PMID- 26140889 TI - Bone Anchor Fixation in Abdominal Wall Reconstruction: A Useful Adjunct in Suprapubic and Para-iliac Hernia Repair. AB - Suprapubic hernias, parailiac or flank hernias, and lumbar hernias are difficult to repair and are associated with high-recurrence rates owing to difficulty in obtaining substantive overlap and especially mesh fixation due to bone being a margin of the hernia. Orthopedic suture anchors used for ligament reconstruction have been used to attach prosthetic material to bony surfaces and can be used in the repair of these hernias where suture fixation was impossible. A prospective, single institution study of ventral hernia repairs involving bone anchor mesh fixation was performed. Demographics, operative details, and outcomes data were collected. Twenty patients were identified, with a mean age 53 (range: 35-70 years) and mean body mass index 28.4 kg/m(2) (range 21-38). Ten lumbar, seven suprapubic, and three parailiac hernias were studied. The majority were recurrent hernias (n = 13), with one to seven previously failed repairs. The mean hernia defect size was very large (270 cm(2); range: 56-832 cm(2)) with average mesh size of 1090 cm(2) (range 224-3640 cm(2)). Both Mitek GII (Depuy, Raynham, MA) and JuggerKnot 2.9-mm (Biomet, Biomedical Instruments, Warsaw, IN) anchors were used, with an average of four anchors/case (range: 1-16). Mean operative time was 218 minutes (120-495). There were three minor complications, no operative mortality, and no recurrences during an average follow-up of 24 months. Pelvic bone anchors permit mesh fixation in high-recurrence areas not amenable to traditional suture fixation. The ability to safely and effectively use bone anchor fixation is an essential tool in complex open ventral hernia repair. PMID- 26140890 TI - How to Further Decrease the Efficiency of Care at a Level I Trauma Center: Implement the Amended Resident Work Hours. AB - Work-hour restrictions were amended in 2011 to limit interns to 16 continuous duty hours, essentially requiring a night float system of 12-hour shifts. We hypothesize that there has been no improvement in outcomes after implementation of the amended work-hour restrictions. Outcomes from trauma admissions were queried from the trauma registry from 2009 to 2011 (PRE) and 2011 to 2013 (POST). The primary outcome was mortality with secondary outcomes intensive care unit length of stay (LOS)and LOS. Patients were stratified based on age, mechanism, gender, blood pressure, heart rate, and injury severity (Injury Severity Score, Glasgow Coma Scale, Base Deficit). Outcomes were then compared from admissions PRE to POST. A total of 9178 patients were included in the study population. The mean age was 42 with most being male (72%) and blunt mechanism (81%). Patient populations were well matched except patients in the POST period were slightly older (43 vs 42 years; P = 0.01). Intensive care unit LOS and LOS were higher in the POST period. After adjusted analysis, admission in the POST period was not a predictor of mortality (odds ratio 0.857; confidence interval 0.655-1.12). The POST period was an independent predictor for LOS (beta = 0.74; P = 0.002). This study adds to the mounting evidence that the implementation of the amended limits on work hours leads to furthermore decreased efficiency of care. PMID- 26140891 TI - Local Anesthesia in Open Inguinal Hernia Repair Improves Postoperative Quality of Life Compared to General Anesthesia: A Prospective, International Study. AB - The choice of general (GA) versus local anesthesia (LA) in open inguinal hernia repair (OIHR) has a substantial financial impact and may influence clinical outcomes. Our study compares postoperative quality of life (QOL) in patients undergoing OIHR under LA versus GA. A cooperative prospective study from centers in 10 countries was performed through the International Hernia Mesh Registry from 2007 to 2012. QOL was compared at one, six, 12, and 24 months for LA versus GA with univariate and multivariate analysis controlling for known confounding variables. Of 1128 patients who underwent OIHR, 585(52%) used GA and 533(48%) used LA. Most were male (92%) with unilateral (94%), primary (91%) repairs with a mean age 57 +/- 16 years. There was no difference (P > 0.05) in age, gender, operative time, mesh size, length of stay, infection, recurrence, reoperation, or death. Multivariate analysis demonstrated significant QOL differences between groups: GA had higher odds of discomfort at one and six months [odds ratio (OR) 3.3, 2.0], movement limitation at one and six months (OR 3.5, 2.8), and mesh sensation at one and 12 months (OR 2.9, 1.8). Overall, patients undergoing OIHR under LA had improved postoperative QOL in the short and long term compared with GA. PMID- 26140892 TI - Quality Metrics in Surgery Resident Performance of Screening Colonoscopy. AB - In an attempt to further standardize surgical training, the American Board of Surgery now requires that residents provide evidence that they are certified in flexible endoscopy. This prospective study was designed to determine whether, through a structured curriculum, junior level residents could learn to conduct competent and safe screening colonoscopy (SC). An Institutional Review Board approved prospective analysis of SC performed by five postgraduate year-2 residents during the 2012-2013 academic year was completed. All SC were performed under direct supervision of one of the two surgical endoscopists after each resident passed a structured endoscopy simulation curriculum. The following metrics of the American Society for Gastrointestinal Endoscopy and the American College of Gastroenterology were recorded: bowel prep quality; cecal intubation; withdrawal time; number of visualized polyps; procedural duration; final pathology; adenoma detection rate (ADR); and, complications. Power analysis revealed that 108 procedures were required for an 80 per cent probability of data analysis accuracy. (American Society for Gastrointestinal Endoscopy ASGE/American College of Gastroenterology benchmark values in parentheses): 166 colonoscopies were performed, of which 149 met inclusion criteria. Bowel prep was considered "excellent" or "good" in 90 per cent of cases. The cecum was reached in 96 per cent of cases. Mean withdrawal time was 12 minutes (>=6 minute). Average procedure time was 30 minutes (<= 30 minute). Polyp(s) were visualized and removed in 30 per cent of patients. The overall adenoma detection rate was 22.8 per cent (>20%). The ADR for males was 29.5 per cent (>25%). The ADR for females was 18.2 per cent (>15%). Average polyp size was 7.7 mm (range: 2-25 mm). No patients were readmitted for bleeding or perforation. Within a structured learning environment, trained surgical endoscopists can teach junior level surgery residents to perform safe and competent screening colonoscopy. PMID- 26140893 TI - Outcomes of Laparoscopic versus Open Fascial Component Separation for Complex Ventral Hernia Repair. AB - Ventral hernia recurrence rates have improved with advancements in technique. Open and laparoscopic fascial component separation techniques improve recurrence rates by allowing a tension free closure. This study examines laparoscopic component separation (LCS) and open component separation (OCS) techniques in the repair of complex ventral hernias and compares factors affecting patient outcomes. A retrospective chart review of patients who underwent ventral hernia repair with LCS and OCS was conducted between 2009 and 2013. Patient characteristics and outcomes were documented. Hernia recurrence was determined using physical exam and computed tomography if physical exam was equivocal. Univariate and multivariate analyses were performed. Ten patients underwent LCS and 38 underwent OCS. The rate of wound infection in the LCS group was 20 per cent versus 50 per cent in the OCS group. The overall rate of recurrence after LCS was 20 per cent, and 26 per cent in the OCS group. For body mass index > 30, the recurrence rate was 20 per cent in the LCS group and 29 per cent (P = 0.5) in the open group. The use of LCS demonstrates a trend in the reduction of hernia recurrence and wound infection overall and in patients with body mass index > 30 compared with OCS. PMID- 26140894 TI - The Role of Magnetic Resonance Cholangiopancreatography in the Diagnosis of Choledocholithiasis: Do Benefits Outweigh the Costs? AB - Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard in evaluation of the biliary tree for choledocholithiasis. Formal indications for magnetic resonance cholangiopancreatography (MRCP) in suspected choledocholithiasis are lacking. Our objective was to determine if MRCP affects management of patients who otherwise would undergo ERCP. A review was conducted of all MRCPs and ERCPs at our institution from 2008 to 2012 with suspected choledocholithiasis. Patients who underwent MRCP and ERCP were compared with those who underwent ERCP alone. Demographic data were collected and notation of whether a post-MRCP ERCP occurred was the primary variable. MRCP was performed in 107 patients for choledocholithiasis. Eighty-eight patients were negative for choledocholithiasis (82%) and 76 were discharged without ERCP (71%). Thirty-one patients received a diagnosis of choledocholithiasis and were referred for ERCP. Of the 19 patients with MRCP-diagnosed common bile duct stones, 95 per cent were confirmed by ERCP (odds ratio 18.0, P < 0.05; agreement 77%, sensitivity 0.76, specificity 0.86, positive predictive value 0.95, negative predictive value 0.50). Length of stay was similar for all groups. A total of 131 patients underwent ERCP without a preprocedural MRCP. Choledocholithiasis was found in 116 patients (92%), whereas 12 patients (9%) had no common bile duct stones and three had an alternate diagnosis. In conclusion, MRCP significantly affected the management of patients who would have undergone ERCP. MRCP did not increase length of stay and contributed to the 95 per cent positivity rate of subsequent ERCPs. These data illustrate the utility of MRCP in suspected choledocholithiasis patients at a low cost with regard to risk and time. PMID- 26140895 TI - Initial Cholecystectomy with Cholangiography Decreases Length of Stay Compared to Preoperative MRCP or ERCP in the Management of Choledocholithiasis. AB - There are several treatments available for choledocholithiasis, but the optimal treatment is highly debated. Some advocate preoperative endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) with cholangiography (IOC). Others advocate initial LC + IOC followed by common bile duct exploration or ERCP. The purpose of this study was to determine whether initial LC + IOC had a shorter length of stay (LOS) compared with preoperative magnetic resonance cholangiopancreatography (MRCP) or ERCP. Patients who underwent cholecystectomy between 2012 and 2013 at two institutions were reviewed. Patients were selected if they had suspected choledocholithiasis, indicated by dilated CBD and/or elevated bilirubin, or confirmed choledocholithiasis. They were excluded if they had pancreatitis or cholangitis. There were 126 patients with suspected choledocholithiasis in this study. Of these, 97 patients underwent initial LC +/- IOC with an average LOS of 3.9 days. IOC was negative in 47.4 per cent patients, and they had a shorter LOS compared with positive IOC patients (2.93 vs 4.82, P < 0.001). Laparoscopic common bile duct exploration was successful in 64.7 per cent and had a shorter LOS compared with postoperative ERCP patients (P = 0.01). Preoperative MRCP was performed in 21 patients with an average LOS of 6.48 days. Preoperative ERCP was performed in eight patients with an average LOS of seven days. Initial LC+IOC is associated with a shorter LOS compared to preoperative MRCP or ERCP. It is recommended as the optimal treatment choice for suspected choledocholithiasis. PMID- 26140896 TI - Association between Interruptions in Chemical Prophylaxis and VTE Formation. AB - Venous thromboembolisms (VTE) are considered preventable events with appropriate mechanical or chemical prophylaxis. However, chemical prophylaxis is frequently delayed or interrupted during hospitalization. We investigated the impact of delayed initiation and interruption of chemical prophylaxis on VTE rates. The incidence of VTE at an urban academic medical center was measured in patients hospitalized for >2 days between November 2013 and May 2014. Patients receiving prophylaxis were grouped as complete (started within 24 hours of admission and no interruptions), delayed (started >24 hours and no interruptions), and interrupted (interruption for >24 hours with or without delay). There were 9961 hospital admissions and 33 VTE (3.3 per 1000 admissions). 25.2 per cent had complete, 16.4 per cent had delayed, and 11.8 per cent had interrupted prophylaxis. 36.8 per cent received no prophylaxis. Interrupted prophylaxis was associated with more VTE than complete (10.2 vs 2.0 per 1000, P < 0.01) and 5.2 greater odds. Admission to a surgical service and prolonged hospital stay were independently associated with increased likelihood of VTE. There was a lower likelihood of getting complete prophylaxis among patients admitted to orthopedic, transplant, cardiac, plastic, and vascular surgery. Surgical patients are at higher risk for VTE and interruptions in VTE prophylaxis significantly increase the risk of VTE. PMID- 26140897 TI - Pyloroplasty for Refractory Gastroparesis. AB - Gastroparesis is a chronic gastric motility disorder in which the pathophysiology mimics a postvagotomy state. Pyloroplasty is beginning to emerge as a successful drainage procedure for refractory gastroparesis. Here we report our experience using pyloroplasty in the surgical management of diabetic and nondiabetic gastroparesis. A retrospective study was performed of 46 patients undergoing pyloroplasty for refractory gastroparesis from January 2010 through December 2013. Gastric emptying scintigraphy and the Gastroparesis Cardinal Symptom Index were assessed pre- and postoperatively. Laparoscopic pyloroplasty was performed in 42 patients, open pyloroplasty in three, and one patient was converted from laparoscopic to open pyloroplasty. Studies were repeated during the six to 12 month postoperative interval. The postoperative gastric emptying scintigraphy improved in 90 per cent of patients and normalized in 60 per cent. Postoperative T1/2 was significantly reduced (P = 0.001) as was four-hour retention (P < 0.001). The Gastroparesis Cardinal Symptom Index showed statistically significant reduction in symptom severity for all nine categories (P < 0.0005) as well as total symptom score (P < 0.005). No patients developed dumping syndrome. Pyloroplasty is a highly effective therapy for refractory gastroparesis, offering significant reduction in symptom severity, improvement in quality of life, and acceleration of gastric emptying. PMID- 26140898 TI - The Relationship of Endoscopic Proficiency to Educational Expense for Virtual Reality Simulator Training Amongst Surgical Trainees. AB - With the introduction of Fundamentals of Endoscopic Surgery, training methods in flexible endoscopy are being augmented with simulation-based curricula. The investment for virtual reality simulators warrants further research into its training advantage. Trainees were randomized into bedside or simulator training groups (BED vs SIM). SIM participated in a proficiency-based virtual reality curriculum. Trainees' endoscopic skills were rated using the Global Assessment of Gastrointestinal Endoscopic Skills (GAGES) in the patient care setting. The number of cases to reach 90 per cent of the maximum GAGES score and calculated costs of training were compared. Nineteen residents participated in the study. There was no difference in the average number of cases required to achieve 90 per cent of the maximum GAGES score for esophagogastroduodenoscopy, 13 (SIM) versus11 (BED) (P = 0.63), or colonoscopy 21 (SIM) versus 4 (BED) (P = 0.34). The average per case cost of training for esophagogastroduodenoscopy was $35.98 (SIM) versus $39.71 (BED) (P = 0.50), not including the depreciation costs associated with the simulator ($715.00 per resident over six years). Use of a simulator appeared to increase the cost of training without accelerating the learning curve or decreasing faculty time spent in instruction. The importance of simulation in endoscopy training will be predicated on more cost-effective simulators. PMID- 26140899 TI - Peritoneal Decortication: An Innovative Technique for Treatment of Obstructive Sclerosing Encapsulating Peritonitis. PMID- 26140900 TI - A CD44 specific peptide developed by phage display for targeting gastric cancer. AB - OBJECTIVE: To develop a peptide probe that could be used for gastric cancer detection via binding to CD44 protein with specificity and affinity. RESULTS: A 12-mer phage peptide library was screened against immobilized CD44 protein. Bound phage counts using ELISA were performed to identify phage clones carrying the most highly selective peptide, which termed RP-1. Immunofluorescence and flow cytometry analysis indicated that the consensus peptide RP-1 could bind to CD44 positive gastric cancer cells with mean fluorescence intensities significantly higher than that of CD44-negative cells. CD44 knockdown led to decreased binding activity of RP-1 to the same cell line. Tissue array technique was used to identify the relationship (r = 0.556) between peptide binding and CD44 detection on gastric cancer tissues. Further, the hyaluronan-binding domain of CD44 was docked with RP-1 using computer modeling/docking approaches, revealing a RP 1/CD44 interaction with geometrical and energy match (-8.6 kcal/mol). CONCLUSIONS: The RP-1 peptide we screened exhibits affinity and specificity to CD44 on cells and has the potential to be used as a candidate probe for gastric cancer cell targeting. PMID- 26140901 TI - Specific gamma-aminobutyric acid decomposition by gabP and gabT under neutral pH in recombinant Corynebacterium glutamicum. AB - OBJECTIVES: Corynebacterium glutamicum that expresses the exogenous L-glutamate decarboxylase (GAD) gene can synthesize gamma-aminobutyric acid (GABA). To prevent GABA decomposition in the recombinant C. glutamicum GAD strain, GABA uptake and the GABA shunt pathway were blocked. RESULTS: GABA uptake is catalyzed by GABA permease encoded by gabP. The first reaction of the GABA shunt pathway is catalyzed by the GABA transaminase encoded by gabT. Initially, the effects of pH on GABA decomposition in recombinant C. glutamicum co-expressing two GAD genes (gadB1 and gadB2) were analyzed, demonstrating that GABA could be decomposed under neutral pH. Next, the gabP and gabT were individually deleted, and the GABA production of the related GAD strains was investigated by controlling the pH of the final fermentation stage at a neutral state. During this stage, the GABA concentration of the gabT-deleted GAD strain decreased from 23.9 +/- 1.8 to 17.7 +/- 0.7 g/l. However, the GABA concentration of the gabP-deleted GAD strain remained at 18.6-19.4 g/l. CONCLUSION: This study demonstrated that GABA was decomposed under neutral pH and that the deletion of gabP could effectively alleviate GABA decomposition in C. glutamicum. PMID- 26140902 TI - A paper-based scaffold for enhanced osteogenic differentiation of equine adipose derived stem cells. AB - OBJECTIVES: We investigated the applicability of single layer paper-based scaffolds for the three-dimensional (3D) growth and osteogenic differentiation of equine adipose-derived stem cells (EADSC), with comparison against conventional two-dimensional (2D) culture on polystyrene tissue culture vessels. RESULTS: Viable culture of EADSC was achieved using paper-based scaffolds, with EADSC grown and differentiated in 3D culture retaining high cell viability (>94 %), similarly to EADSC in 2D culture. Osteogenic differentiation of EADSC was significantly enhanced in 3D culture, with Alizarin Red S staining and quantification demonstrating increased mineralisation (p < 0.0001), and an associated increase in expression of the osteogenic-specific markers alkaline phosphatase (p < 0.0001), osteopontin (p < 0.0001), and runx2 (p < 0.01). Furthermore, scanning electron microscopy revealed a spherical morphology of EADSC in 3D culture, compared to a flat morphology of EADSC in 2D culture. CONCLUSIONS: Single layer paper-based scaffolds provide an enhanced environment for the in vitro 3D growth and osteogenic differentiation of EADSC, with high cell viability, and a spherical morphology. PMID- 26140903 TI - Lymphoid-Like Structures with Distinct B Cell Areas in Kidney Allografts are not Predictive for Graft Rejection. A Non-human Primate Study. AB - Kidney allograft biopsies were analyzed for the presence of B cell clusters/aggregates using CD20 staining. Few B cells were found in the diffuse interstitial infiltrates, but clusters of B cells were found in nodular infiltrates. These nodular infiltrates were smaller shortly after transplantation, and their size increased over time. At the time of clinical rejection, the nodules often presented as tertiary lymphoid structures (TLS) with lymphoid-like follicles. The presence of small B cell clusters during the first 2 months after transplantation was not associated with early rejection. Even in animals that did not reject their allograft, TLS-like structures were present and could disappear over time. Although TLS were more often found in samples with interstitial fibrosis and tubular atrophy (IFTA), TLS were also present in samples without IFTA. The presence and density of clusters resembling tertiary lymphoid structures most likely reflect an ongoing immune response inside the graft and do not necessarily signify a poor graft outcome or IFTA. PMID- 26140906 TI - Editorial Introduction. PMID- 26140905 TI - Assessment of nocturnal sleep architecture by actigraphy and one-channel electroencephalography in early infancy. AB - OBJECTIVE: To elucidate characteristic sleep architecture of different nocturnal sleep patterns in early infancy. METHODS: Participants were 27 infants at the same conceptional age of 3-4months. Nocturnal sleep of these infants was monitored at home by simultaneously using actigraphy and a one-channel portable EEG device. According to the infants' activity for 6h from sleep onset, each night's sleep pattern was classified into three categories: sleeping through the night (STN), sleeping with weak signals (crying/fuss episodes <10min or fed), and sleeping with strong signals (crying/fuss episodes?10min). Associations of sleep patterns with sleep variables (percentage of time in sleep stages, pattern of slow-wave sleep (SWS) recurrence, etc.) were investigated. RESULTS: Analysis was conducted in 95 nights. STN pattern (n=36) was characterized by suppressed body movements while EEG represented a state of wakefulness. Weak signal pattern (n=27) tended to indicate rich and regular distributions of SWS across the night. Strong signal pattern (n=32) was characterized by reduced sleep time, although the amount of SWS was not reduced to that degree. Exclusively breastfed infants accounted for 78% of weak signal patterns, whereas formula-feeding infants, 67% of STN patterns. In several nights with STN or strong signal pattern, SWS did not occur in >50% of the sleep cycles. Multiple regression analysis showed that exclusive breastfeeding may increase the proportion of SWS in non-REM sleep. CONCLUSIONS: Each nocturnal sleep pattern was associated with some sleep architecture, part of which would be attributed to infant's feeding methods. PMID- 26140907 TI - The Historical Perspective: Sheldon Reed and 50 Years of Genetic Counseling. PMID- 26140904 TI - Riparin B, a Synthetic Compound Analogue of Riparin, Inhibits the Systemic Inflammatory Response and Oxidative Stress in Mice. AB - The aim of our study was to evaluate the anti-inflammatory, anti-nociceptive, and anti-oxidant action of Riparin B in vivo. We performed experiments in which we induced paw edema by carrageenan and other mediators, carrageenan-induced peritonitis and the level of myeloperoxidase (MPO) activity, pro-inflammatory cytokines (TNF-alpha and IL-1beta), malondialdehyde (MDA) acid, and glutathione (GSH) from the peritoneal fluid. We also performed behavior tests such as acetic acid-induced writhing, formalin-induced linking, and the hot plate test. Among the doses tested of the Riparin B (1, 3, and 10 mg/kg), the dose of 10 mg/kg showed the strongest effect, and this dose was able to reduce the paw edema induced by carrageenan, dextran, histamine serotonin, bradykinin, 48/80, and PGE2. Similarly, the Riparin B in the same dose reduced cell migration and significantly decreased the nociception induced by formalin and acetic acid and reversed the parameters of the oxidative stress. Thus, we can infer that Riparin B exhibits anti-inflammatory, anti-nociceptive, and anti-oxidant actions in vivo. PMID- 26140908 TI - Psychological Aspects of Genetic Counseling. X. Advanced Counseling Techniques. AB - Four procedures commonly used by experienced counselors are described: simple interview formulations, helping clients think through their problems, reframing, and role playing. Each procedure is illustrated by examples. Among other things, the goal of these procedures is to promote the autonomy and self-directedness of clients and thus are particularly valuable in circumstances requiring a nondirective stance. The need is underscored for a more active counseling stance appropriate to the psychological and problem-solving needs of genetic counselees. PMID- 26140909 TI - Introduction to Update and Review-A New Feature for the Journal. PMID- 26140911 TI - Nonparticipation in Huntington's Disease Predictive Testing: Reasons for Caution in Interpreting Findings. AB - When given the opportunity to clarify their genetic status, most individuals at risk for Huntington's disease (HD) currently show a preference not to know. Our understanding of the characteristics of those who do not request HD predictive testing, and the factors influencing their decision, lags behind our knowledge of test applicants. In the light of our experience with interviewing a random sample of nonparticipants in an ongoing study, we critically analyze research concerning the differences between participants and nonparticipants in HD predictive testing programs and the interpretive characterization of these two groups. The findings concerning nonparticipants are limited to a small sample of the at-risk population, with the problems of biased samples and low response rates. We discuss this and other aspects of research in this area, notably the context and timing of data collection and the predominantly questionnaire-based methodology, that lead us to interpret the conclusions drawn about these two groups with caution. PMID- 26140910 TI - Update and Review: Maternal Serum Screening. AB - Maternal serum levels of alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) can be used to screen pregnancies for neural tube defects, Down syndrome, Trisomy 18, and pregnancy complications. This article summarizes the most recent information regarding maternal serum screening, including genetic counseling issues. PMID- 26140912 TI - Abstracts of Papers and Posters Presented at the Sixteenth Annual Education Conference of the National Society of Genetic Counselors (Baltimore, Maryland). PMID- 26140913 TI - Genetic Library. PMID- 26140914 TI - Erratum. PMID- 26140916 TI - Stochastic fluctuations in gene expression in aging hippocampal neurons could be exacerbated by traumatic brain injury. AB - Traumatic brain injury (TBI) is a risk factor for age-related dementia and development of neurodegenerative disorders such as Alzheimer's disease that are associated with cognitive decline. The exact mechanism for this risk is unknown but we hypothesized that TBI is exacerbating age-related changes in gene expression. Here, we present evidence in an animal model that experimental TBI increases age-related stochastic gene expression. We compared the variability in expression of several genes associated with cell survival or death, among three groups of laser capture microdissected hippocampal neurons from aging rat brains. TBI increased stochastic fluctuations in gene expression in both dying and surviving neurons compared to the naive neurons. Increases in random, stochastic fluctuations in prosurvival or prodeath gene expression could potentially alter cell survival or cell death pathways in aging neurons after TBI which may lead to age-related cognitive decline. PMID- 26140915 TI - Follow-up after gastrectomy for cancer: the Charter Scaligero Consensus Conference. AB - PURPOSE: Presently, there is no scientific evidence supporting a definite role for follow-up after gastrectomy for cancer, and clinical practices are quite different around the globe. The aim of this consensus conference was to present an ideal prototype of follow-up after gastrectomy for cancer, based on shared experiences and taking into account the need to rationalize the diagnostic course without losing the possibility of detecting local recurrence at a potentially curable stage. METHODS: On June 19-22, 2013 in Verona (Italy), during the 10th International Gastric Cancer Congress (IGCC) of the International Gastric Cancer Association, a consensus meeting was held, concluding a 6-month, Web-based, consensus conference entitled "Rationale of oncological follow-up after gastrectomy for cancer." RESULTS: Forty-eight experts, with a geographical distribution reflecting different health cultures worldwide, participated in the consensus conference, and 39 attended the consensus meeting. Six statements were finally approved, displayed in a plenary session and signed by the vast majority of the 10th IGCC participants. These statements are attached as an annex to the Charter Scaligero on Gastric Cancer. CONCLUSION: After gastrectomy for cancer, oncological follow-up should be offered to patients; it should be tailored to the stage of the disease, mainly based on cross-sectional imaging, and should be discontinued after 5 years. PMID- 26140917 TI - A review of critical factors for assessing the dermal absorption of metal oxide nanoparticles from sunscreens applied to humans, and a research strategy to address current deficiencies. AB - Metal oxide nanoparticles in sunscreens provide broad-spectrum ultraviolet protection to skin. All studies to assess dermal penetration of nanoparticles have unanimously concluded that the overwhelming majority of nanoparticles remain on the outer surface of the skin. However, possibly due to many different experimental protocols in use, conclusions over the potential penetration to viable skin are mixed. Here, we review several factors that may influence experimental results for dermal penetration including the species studied (human, or animal model), size and coating of the metal oxide nanoparticles, composition of the sunscreen formulation, site of sunscreen application, dose and number of applications, duration of the study, types of biological samples analysed, methods for analysing samples, exposure to UV and skin flexing. Based on this information, we suggest an appropriate research agenda involving international collaboration that maximises the potential for dermal absorption of nanoparticles, and their detection, under normal conditions of sunscreen use by humans. If results from this research agenda indicate no absorption is observed, then concerns over adverse health effects from the dermal absorption of nanoparticles in sunscreens may be allayed. PMID- 26140918 TI - Enhanced production of secretory glycoprotein VSTM1-v2 with mouse IgGkappa signal peptide in optimized HEK293F transient transfection. AB - VSTM1-v2 is a secretory glycoprotein identified by our laboratory. Our previous study revealed that VSTM1-v2 could promote differentiation and activation of Th17 cells. To explore the role of VSTM1-v2 in the immune system further, a source of abundant high-quality recombinant protein is warranted. However, high-level expression of bioactive VSTM1-v2 is difficult due to its weak secretion capacity. To obtain sufficient recombinant VSTM1-v2, we developed an improved expression and purification system by replacing the native signal peptide with a mouse IgGkappa signal peptide that did not alter the protein cleavage site. We also optimized parameters for a transient gene expression system in HEK293F cells suspended in serum-free media with polyethyleneimine. Finally, 3.6 mg/L recombinant VSTM1-v2 protein with N-glycosylation and no less than 95% purity was obtained through one-step purification with Ni affinity chromatography. The final yield after purification was increased by more than 7-fold compared to the yield from our previously reported HEK293T system (from 0.5 mg/L to 3.6 mg/L). More importantly, VSTM1-v2 protein exhibited excellent bioactivity. In conclusion, the improved system is not only a dependable source of abundant bioactive VSTM1-v2 for functional studies but also demonstrates a highly efficient approach for enhancing the production of proteins in a short time period, especially for secretory proteins with poor yields. PMID- 26140919 TI - Season of birth is different in Inuit suicide victims born into Traditional than into Modern Lifestyle: a register study from Greenland. AB - BACKGROUND: There is growing evidence that living conditions at birth play a role in medical conditions later in life. Population-based studies from the Northern Hemisphere have shown that persons born in the spring or summer are at greater risk of committing suicide. A statistical correlation with light availability at birth has been observed in past research, but the cause remains unknown. Greenland is one of the most extreme of natural human habitats with regard to seasonal changes in light. The combination of rapid social changes and reliable population statistics offers a unique opportunity to make comparisons between persons born into a Traditional Lifestyle and those born into a Modern Lifestyle. The aim of this work was to assess whether season of birth differed between suicide victims born into an old or into a modern lifestyle. METHODS: Official population and mortality registers were used. Suicide victims born (1903-1950) into the Traditional Lifestyle were compared with those born into the Modern Lifestyle (1961-1980). Rayleigh's test for circular distributions was used to assess the season of birth in suicide victims. Data regarding season of birth in the general population were collected. RESULTS: Persons born in March-June in the Traditional Lifestyle were much less likely to commit suicide than those born during other periods of the year. This is contrary to the findings of other studies. The seasonal differences had disappeared for those born into the Modern Lifestyle. The suicide rate increased from very low rates to about 140 suicides/100 000 person-years in the 1980s. CONCLUSIONS: The reason behind a variation in season of birth in suicide victims born into the old lifestyle is unknown. It is also unknown why the seasonal difference had disappeared with modern lifestyle. Possible influence of artificial light, nutrition, microbiota and seasonal infections are discussed. The underlying causes behind suicides may be different in traditional and modern Greenland. PMID- 26140920 TI - Validation of two prediction models of undiagnosed chronic kidney disease in mixed-ancestry South Africans. AB - BACKGROUND: Chronic kidney disease (CKD) is a global challenge. Risk models to predict prevalent undiagnosed CKD have been published. However, none was developed or validated in an African population. We validated the Korean and Thai CKD prediction model in mixed-ancestry South Africans. METHODS: Discrimination and calibration were assessed overall and by major subgroups. CKD was defined as 'estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)' or 'any nephropathy'. eGFR was based on the 4-variable Modification of Diet in Renal Disease (MDRD) formula. RESULTS: In all 902 participants (mean age 55 years) included, 259 (28.7 %) had prevalent undiagnosed CKD. C-statistics were 0.76 (95 % CI: 0.73-0.79) for 'eGFR <60 ml/min/1.73 m(2)' and 0.81 (0.78-0.84) for 'any nephropathy' for the Korean model; corresponding values for the Thai model were 0.80 (0.77-0.83) and 0.77 (0.74-0.81). Discrimination was better in men, older and normal weight individuals. The model underestimated CKD risk by 10 % to 13 % for the Thai and 9 % to 93 % for the Korean model. Intercept adjustment significantly improved the calibration with an expected/observed risk of 'eGFR <60 ml/min/1.73 m(2)' and 'any nephropathy' respectively of 0.98 (0.87-1.10) and 0.97 (0.86-1.09) for the Thai model; but resulted in an underestimation by 24 % with the Korean model. Results were broadly similar for CKD derived from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. CONCLUSION: Asian prevalent CKD risk models had acceptable performances in mixed-ancestry South Africans. This highlights the potential importance of using existing models for risk CKD screening in developing countries. PMID- 26140921 TI - Platelet hyperactivity and fibrin clot structure in transient ischemic attack individuals in the presence of metabolic syndrome: a microscopy and thromboelastography study. AB - BACKGROUND: Strokes are commonly preceded by transient ischemic attacks (TIAs). TIA is often associated with metabolic syndrome (causing chronic inflammation), resulting in a proinflammatory- and procoagulant-environment. The aim of this study was to determine whether platelet- and fibrin network-morphology or coagulation profiles of individuals that suffered a TIA in the presence of metabolic syndrome was altered when compared to healthy individuals. MATERIALS AND METHODS: The study consisted of 40 voluntary participants. Twenty individuals that suffered a TIA in the previous 48 h with at least two metabolic syndrome risk factors present and twenty healthy age-matched controls. Scanning electron- and atomic force microscopy was used to study platelet- and fibrin-morphology, atomic force microscopy was used to study platelet- and fibrin fiber-elasticity and thromboelastography for the study of coagulation profiles. Statistical analysis was performed to compare the two groups. In all cases a p-value of less than 0.05 was considered statistically significant. RESULTS: Platelets of the control group appeared spherical with few pseudopodia present while the platelets of the TIA individuals presented with numerous pseudopodia and spreading, indicating activation. Platelet aggregation was also present. The fibrin networks of the healthy individuals consist of thick and thin fibers that form an organized network of fibers. The fibrin networks of the TIA individuals appeared less organized with less taut fibers. Fibrin fiber thickness was found to be significantly increased in the TIA group (p-value <0.001) when compared to healthy controls. The thicker fibers formed irregular networks with thick masses of fibrin fibers. Platelet and fibrin fiber elasticity was found to be significantly lower in the experimental group (p-value 0.0042 and p-value 0.0007 respectively). The hemostatic profiles of the diseased individuals did not differ significantly (p-value > 0.05) from the healthy controls, indicating a normal functioning coagulation cascade. CONCLUSION: The findings indicate that pathological clot formation is not caused by alterations in the coagulation cascade but rather by the premature activation of platelets (as a result of chronic inflammation) that in turn causes altered fibrin formation. PMID- 26140922 TI - Updated estimate of the duration of the meningo-encephalitic stage in gambiense human African trypanosomiasis. AB - BACKGROUND: The duration of the stages of HAT is an important factor in epidemiological studies and intervention planning. Previously, we published estimates of the duration of the haemo-lymphatic stage 1 and meningo-encephalitic stage 2 of the gambiense form of human African trypanosomiasis (HAT), in the absence of treatment. Here we revise the estimate of stage 2 duration, computed based on data from Uganda and South Sudan, by adjusting observed infection prevalence for incomplete case detection coverage and diagnostic inaccuracy. FINDINGS: The revised best estimate for the mean duration of stage 2 is 252 days (95% CI 171-399), about half of our initial best estimate, giving a total mean duration of untreated gambiense HAT infection of approximately 2 years and 2 months. CONCLUSIONS: Our new estimate provides improved information on the transmission dynamics of this neglected tropical disease in Uganda and South Sudan. We stress that there remains considerable variability around the estimated mean values, and that one must be cautious in applying these results to other foci. PMID- 26140923 TI - Stool metatranscriptomics: A technical guideline for mRNA stabilisation and isolation. AB - BACKGROUND: The complex microbiome of the gut has an enormous impact on human health. Analysis of the transcriptional activity of microorganisms through mRNA sequencing (metatranscriptomics) opens a completely new window into their activity in vivo, but it is highly challenging due to numerous technical and bioinformatical obstacles. Here we present an optimized pipeline for extraction of high quality mRNA from stool samples. RESULTS: Comparison of three commercially available RNA extraction kits with the method of Zoetendal revealed that the Powermicrobiome Kit (MoBio) performed best with respect to RNA yield and purity. Next, the influence of the stabilization reagent during sample storage for up to 15 days was studied. RIN analysis and qRT-PCR of spiked-in and indigenous genes revealed that RNA Later preserved mRNA integrity most efficiently, while samples conserved in RNA Protect showed substantial mRNA decay. Using the optimized pipeline developed here, recovery rates for spiked-in E.coli cells expressing fluorescing proteins were 8.7-9.7% for SuperfolderGFP and 14.7-17.8% for mCherry. The mRNA of stabilized stool samples as well as of snap frozen controls was sequenced with Illumina Hiseq, yielding on average 74 million reads per sample. PCoA analysis, taxonomic classification using Kraken and functional classification using bwa showed that the transcriptomes of samples conserved in RNA Later were unchanged for up to 6 days even at room temperature, while RNA Protect was inefficient for storage durations exceeding 24 h. However, our data indicate that RNA Later introduces a bias which is then maintained throughout storage, while RNA Protect conserved samples are initially more similar to the snap frozen controls. RNA Later conserved samples had a reduced abundance of e.g. Prevotellaceae transcripts and were depleted for e.g. COG category "Carbohydrate transport and metabolism". CONCLUSION: Since the overall similarity between all stool transcriptional profiles studied here was >0.92, these differences are unlikely to affect global comparisons, but should be taken into account when rare but critically important members of the stool microbiome are being studied. PMID- 26140924 TI - Localization, quantification and interaction with host factors of endogenous HTLV 1 HBZ protein in infected cells and ATL. AB - BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of a severe form of neoplasia designated Adult T cell Leukaemia (ATL). It is widely accepted that the viral transactivator Tax-1 is the major viral product involved in the onset, but not in the maintenance, of neoplastic phenotype, as only 30-40% of ATL cells express Tax-1. It has been recently demonstrated that HBZ (HTLV-1 bZIP factor), a protein encoded by the minus strand of HTLV-1 genome, constantly expressed in infected cells and in ATL tumor cells, is also involved in the pathogenesis of leukaemia. The full role played by HBZ in oncogenesis is not clarified in detail also because of the limited availability of tools to assess quantitative expression, subcellular location and interaction of HBZ with host factors in ATL. RESULTS: By the use of the first reported monoclonal antibody against HBZ, 4D4-F3, generated in our laboratory it has been possible to carefully assess for the first time the above parameters in HTLV-1 chronically infected cells and, most importantly, in fresh leukemic cells from patients. Endogenous HBZ is expressed in speckle-like structures localized in the nucleus. The calculated number of endogenous HBZ molecules varies between 17.461 and 39.615 molecules per cell, 20- to 50-fold less than the amount expressed in HBZ transfected cells used by most investigators to assess the expression, function and subcellular localization of the viral protein. HBZ interacts in vivo with p300 and JunD and co-localizes only partially, and depending on the amount of expressed HBZ, not only with p300 and JunD but also with CBP and CREB2. CONCLUSIONS: The possibility to study endogenous HBZ in detail may significantly contribute to a better delineation of the role of HBZ during HTLV-1 infection and cellular transformation. PMID- 26140925 TI - Mitochondrial fusion/fission process involved in the improvement of catalpol on high glucose-induced hepatic mitochondrial dysfunction. AB - Catalpol, an iridoid glycoside, has been shown to exert hypoglycemic effect by rescuing mitochondrial function, but the detailed mechanism remains unclear yet. In this study, the effect and mechanism of catalpol on the hepatic mitochondria under diabetic conditions were further examined. Oral administration of catalpol significantly reduced the blood glucose, triglyceride, and cholesterol levels in high-fat diet- and streptozotocin-induced diabetic mice. Additionally, catalpol attenuated the decrease in liver mitochondrial ATP content resulting from diabetes. Furthermore, the number of mitochondria possessing a long size was increased in catalpol-treated mice. Interestingly, the catalpol-induced recovery of mitochondrial function was associated with decreased fission protein 1 and dynamin-related protein 1 expression as well as increased mitofusin 1 expression in the liver. In HepG2 cells, catalpol alleviated the decrease of ATP content and mitochondrial membrane potential, and the increase of reactive oxygen species formation induced by high glucose. MitoTracker Green stain shows that the tubular feature of mitochondria was maintained when cells were treated with catalpol. Catalpol also decreased fission protein 1 and dynamin-related protein 1 expression and increased mitofusin 1 expression in HepG2 cells. The present results suggest that catalpol can ameliorate hepatic mitochondrial dysfunction under a diabetic state, and this may be related to its regulation of mitochondrial fusion and fission events. PMID- 26140926 TI - Xanthohumol Improves Diet-induced Obesity and Fatty Liver by Suppressing Sterol Regulatory Element-binding Protein (SREBP) Activation. AB - Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that stimulate the expression of genes involved in fatty acid and cholesterol biosynthesis. Here, we demonstrate that a prenylated flavonoid in hops, xanthohumol (XN), is a novel SREBP inactivator that reduces the de novo synthesis of fatty acid and cholesterol. XN independently suppressed the maturation of SREBPs of insulin-induced genes in a manner different from sterols. Our results suggest that XN impairs the endoplasmic reticulum-to-Golgi translocation of the SREBP cleavage-activating protein (SCAP)-SREBP complex by binding to Sec23/24 and blocking SCAP/SREBP incorporation into common coated protein II vesicles. Furthermore, in diet-induced obese mice, dietary XN suppressed SREBP-1 target gene expression in the liver accompanied by a reduction of the mature form of hepatic SREBP-1, and it inhibited the development of obesity and hepatic steatosis. Altogether, our data suggest that XN attenuates the function of SREBP 1 by repressing its maturation and that it has the potential of becoming a nutraceutical food or pharmacological agent for improving metabolic syndrome. PMID- 26140927 TI - Common drugs can affect moral decision making, study finds. PMID- 26140928 TI - EvoDB: a database of evolutionary rate profiles, associated protein domains and phylogenetic trees for PFAM-A. AB - The evolutionary rate at codon sites across protein-coding nucleotide sequences represents a valuable tier of information for aligning sequences, inferring homology and constructing phylogenetic profiles. However, a comprehensive resource for cataloguing the evolutionary rate at codon sites and their corresponding nucleotide and protein domain sequence alignments has not been developed. To address this gap in knowledge, EvoDB (an Evolutionary rates DataBase) was compiled. Nucleotide sequences and their corresponding protein domain data including the associated seed alignments from the PFAM-A (protein family) database were used to estimate evolutionary rate (omega = dN/dS) profiles at codon sites for each entry. EvoDB contains 98.83% of the gapped nucleotide sequence alignments and 97.1% of the evolutionary rate profiles for the corresponding information in PFAM-A. As the identification of codon sites under positive selection and their position in a sequence profile is usually the most sought after information for molecular evolutionary biologists, evolutionary rate profiles were determined under the M2a model using the CODEML algorithm in the PAML (Phylogenetic Analysis by Maximum Likelihood) suite of software. Validation of nucleotide sequences against amino acid data was implemented to ensure high data quality. EvoDB is a catalogue of the evolutionary rate profiles and provides the corresponding phylogenetic trees, PFAM-A alignments and annotated accession identifier data. In addition, the database can be explored and queried using known evolutionary rate profiles to identify domains under similar evolutionary constraints and pressures. EvoDB is a resource for evolutionary, phylogenetic studies and presents a tier of information untapped by current databases. PMID- 26140929 TI - New NICE guidance on referral for cancer. PMID- 26140930 TI - Feasibility and Acceptability of a Brief Motivational Stage-Tailored Intervention to Advance Care Planning: A Pilot Study. AB - AIM: This pilot study explored the feasibility and acceptability of a stage tailored motivational interviewing intervention with education that focuses on changes in end-of-life (EOL) communication, completion of advance directives (ADs), and readiness for advance care planning (ACP). METHODS: One group pretest posttest design was implemented with 30 low-income older adults. RESULTS: This pilot study showed its feasibility in enhancing ACP. Action for ACP-that is, identifying a proxy for decision making and documenting EOL treatment preference in an AD-increased significantly by 23.3% (n = 7). The participants' readiness for ACP, knowledge, self-efficacy, positive attitudes, and perceived importance of ACP increased significantly after the intervention. CONCLUSION: Health care professionals and service providers who interact with older adults should tailor ACP dialogues in accordance with individuals' motivation. PMID- 26140931 TI - Initial Development of a Computer Algorithm to Identify Patients With Breast and Lung Cancer Having Poor Prognosis in a Safety Net Hospital. AB - BACKGROUND: Physicians often have difficulty with prognostication and identification of patients who are in need of counseling about options for care at the end of life. Consequently, the objective of this study was to describe the initial stages in development of a computerized algorithm that will identify breast and lung cancer patients most in need of counseling about care options, including advance care planning, palliative care, and hospice. METHODS: Clinical and non-clinical data were extracted from the electronic medical record of breast and lung cancer patients admitted to a large, urban hospital for the year 2010. These data were used to create an electronic (e-EOL) algorithm designed to identify advanced cancer patients who could benefit from in-depth discussion about end-of-life care options. RESULTS: There were 369 eligible breast (42%) and lung (58%) cancer patients identified by ICD-9 code. The e-EOL algorithm identified 53 (14%) patients that met assigned criteria (presence of metastatic disease and albumin < 2.5 g/dl). The sensitivity, specificity, and positive predictive value of the first generation algorithm were 21%, 96%, and 91% when compared to physician expert chart review. Survival analysis showed that 6-month survival for algorithm positive cases was 46% versus 78% for algorithm negative cases, and 1-year survival was 32% versus 72%, respectively. CONCLUSIONS: Initial testing of the e-EOL algorithm appears to be promising. Other markers of advanced illness will added to the algorithm to improve its test operating characteristics so it may be used to identify patients with poor prognosis in real time. PMID- 26140932 TI - The Implications of Stratigraphic Compatibility for Character Integration among Fossil Taxa. AB - Two characters are stratigraphically compatible if some phylogenies indicate that their combinations (state-pairs) evolved without homoplasy and in an order consistent with the fossil record. Simulations assuming independent character change indicate that we expect approximately 95% of compatible character pairs to also be stratigraphically compatible over a wide range of sampling regimes and general evolutionary models. However, two general models of rate heterogeneity elevate expected stratigraphic incompatibility: "early burst" models, where rates of change are higher among early members of a clade than among later members of that clade, and "integration" models, where the evolution of characters is correlated in some manner. Both models have important theoretical and methodological implications. Therefore, we examine 259 metazoan clades for deviations from expected stratigraphic compatibility. We do so first assuming independent change with equal rates of character change through time. We then repeat the analysis assuming independent change with separate "early" and "late" rates (with "early" = the first third of taxa in a clade), with the early and late rates chosen to maximize the probability of the observed compatibility among the early taxa and then the whole clade. We single out Cambrian trilobites as a possible "control" group because morphometric studies suggest that integration patterns are not conserved among closely related species. Even allowing for early bursts, we see excess stratigraphic incompatibility (i.e., negative deviations) in significantly more clades than expected at 0.50, 0.25, and 0.05 [Formula: see text] values. This pattern is particularly strong in chordates, echinoderms, and arthropods. However, stratigraphic compatibility among Cambrian trilobites matches the expectations of integration studies, as they (unlike post-Cambrian trilobites) do not deviate from the expectations of independent change with no early bursts. Thus, these results suggest that processes such as integration strongly affect the data that paleontologists use to study phylogeny, disparity, and rates. PMID- 26140933 TI - 60 YEARS OF NEUROENDOCRINOLOGY: Celebrating 60 years of neuroendocrinology. PMID- 26140935 TI - Assembling Paramagnetic Ceruloplasmin at Electrode Surfaces Covered with Ferromagnetic Nanoparticles. Scanning Electrochemical Microscopy in the Presence of a Magnetic Field. AB - Adsorption of ceruloplasmin (Cp) at a gold electrode modified with ferromagnetic iron nanoparticles encapsulated in carbon (Fe@C Nps) leads to a successful immobilization of the enzyme in its electroactive form. The proper placement of Cp at the electrode surface on top of the nanocapsules containing an iron core allowed a preorientation of the enzyme, hence allowing direct electron transfer between the electrode and the enzyme. Laser ablation coupled with inductively coupled plasma mass spectrometry indicated that Cp was predominantly located at the paramagnetic nanoparticles. Scanning electrochemical microscopy measurements in the sample-generation/tip-collection mode proved that Cp was ferrooxidative inactive if it was immobilized on the bare gold surface and reached the highest activity if it was adsorbed on Fe@C Nps in the presence of a magnetic field. PMID- 26140934 TI - 60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Geoffrey Harris and my brush with his unit. AB - Geoffrey Harris is chiefly known for his demonstration of the control of the pituitary gland by the portal vessels coming from the hypothalamus. This does not do justice to his extraordinary contribution to biology. Harris' life's work was central in demonstrating the brain/body interactions by which animals and humans adapt to their environment, and above all the control of that most crucial and proximate of all evolutionary events - reproduction. In this brief review, I have tried to put Geoffrey Harris' work in the context of the scientific thinking at the time when he began his work, and above all, the contribution of his mentor, FHA Marshall, on whose towering shoulders Harris rose. But this is mainly my personal story, in which I have tried to show the debt that my work owed to Harris and especially to my dear friend, the late Keith Brown-Grant in Harris' team. I myself was never an endocrinologist, but over a short period in the early 1970s, under the influence of such inspirational mentors, and using purely anatomical methods, I was able to demonstrate sexual dimorphism and hormone dependent sexual differentiation in the connections of the preoptic area, regeneration of the median eminence, the ultrastructure of apoptosis, the requirement for the suprachiasmatic nuclei in reproductive rhythms, the existence of non-rod or cone photoreceptors in the albino rat retina and, later, the expression of vasopressin by solitary (one in 600) magnocellular neurons in the polydipsic di/di Brattleboro mutant rat; this phenomenon was subsequently shown to be due to a+1 reading frameshift. I end this brief overview by mentioning some of the abiding and fascinating mysteries of the endocrine memory of the brain that arise from Harris' work on the control of the endocrines, and by pointing out how the current interest in chronobiology emphasises what a Cinderella the endocrine mechanisms have become in current brain imaging studies. PMID- 26140936 TI - Recommendations on the Use of Echocardiography in Adult Hypertension: A Report from the European Association of Cardiovascular Imaging (EACVI) and the American Society of Echocardiography (ASE). AB - Hypertension remains a major contributor to the global burden of disease. The measurement of blood pressure continues to have pitfalls related to both physiological aspects and acute variation. As the left ventricle (LV) remains one of the main target organs of hypertension, and echocardiographic measures of structure and function carry prognostic information in this setting, the development of a consensus position on the use of echocardiography in this setting is important. Recent developments in the assessment of LV hypertrophy and LV systolic and diastolic function have prompted the preparation of this document. The focus of this work is on the cardiovascular responses to hypertension rather than the diagnosis of secondary hypertension. Sections address the pathophysiology of the cardiac and vascular responses to hypertension, measurement of LV mass, geometry, and function, as well as effects of treatment. PMID- 26140938 TI - A New Strategic Plan for a Thriving Organization. PMID- 26140937 TI - A Summary of the American Society of Echocardiography Foundation Value-Based Healthcare: Summit 2014: The Role of Cardiovascular Ultrasound in the New Paradigm. AB - Value-Based Healthcare: Summit 2014 clearly achieved the three goals set forth at the beginning of this document. First, the live event informed and educated attendees through a discussion of the evolving value-based healthcare environment, including a collaborative effort to define the important role of cardiovascular ultrasound in that environment. Second, publication of these Summit proceedings in the Journal of the American Society of Echocardiography will inform a wider audience of the important insights gathered. Third, moving forward, the ASE will continue to build a ''living resource'' on its website, http://www.asecho.org, for clinicians, researchers, and administrators to use in advocating for the value of cardiovascular ultrasound in the new value-based healthcare environment. The ASE looks forward to incorporating many of the Summit recommendations as it works with its members, legislators, payers, hospital administrators, and researchers to demonstrate and increase the value of cardiovascular ultrasound. All Summit attendees shared in the infectious enthusiasm generated by this proactive approach to ensuring cardiovascular ultrasound's place as ''The Value Choice'' in cardiac imaging. PMID- 26140939 TI - Passing the Torch of Leadership-The Bridge of Continued Excellence. PMID- 26140940 TI - Echo, the Cardiac Operating Room, and Intraoperative Echocardiography. PMID- 26140941 TI - Structure and properties of the catalytic site of nitric oxide reductase at ambient temperature. AB - Nitric oxide reductase (Nor) is the third of the four enzymes of bacterial denitrification responsible for the catalytic formation of laughing gas (N2O). Here we report the detection of the hyponitrite (HO-N=N-O(-)) species (nuN N=1332cm(-1)) in the heme b3 Fe-FeB dinuclear center of Nor from Paracoccus denitrificans. We have also applied density functional theory (DFT) to characterize the bimetallic-bridging hyponitrite species in the reduction of NO to N2O by Nor and compare the present results with those recently reported for the N-N bond formation in the ba3 and caa3 oxidoreductases from Thermus thermophilus. PMID- 26140942 TI - Functional characterization and organ distribution of three mitochondrial ATP Mg/Pi carriers in Arabidopsis thaliana. AB - The Arabidopsis thaliana genome contains 58 membrane proteins belonging to the mitochondrial carrier family. Three members of this family, here named AtAPC1, AtAPC2, and AtAPC3, exhibit high structural similarities to the human mitochondrial ATP-Mg(2+)/phosphate carriers. Under normal physiological conditions the AtAPC1 gene was expressed at least five times more than the other two AtAPC genes in flower, leaf, stem, root and seedlings. However, in stress conditions the expression levels of AtAPC1 and AtAPC3 change. Direct transport assays with recombinant and reconstituted AtAPC1, AtAPC2 and AtAPC3 showed that they transport phosphate, AMP, ADP, ATP, adenosine 5'-phosphosulfate and, to a lesser extent, other nucleotides. AtAPC2 and AtAPC3 also had the ability to transport sulfate and thiosulfate. All three AtAPCs catalyzed a counter-exchange transport that was saturable and inhibited by pyridoxal-5'-phosphate. The transport activities of AtAPCs were also inhibited by the addition of EDTA or EGTA and stimulated by the addition of Ca(2+). Given that phosphate and sulfate can be recycled via their own specific carriers, these findings indicate that AtAPCs can catalyze net transfer of adenine nucleotides across the inner mitochondrial membrane in exchange for phosphate (or sulfate), and that this transport is regulated both at the transcriptional level and by Ca(2+). PMID- 26140943 TI - Investigating the Effect of a Single Infusion of Reconstituted High-Density Lipoprotein in Patients with Symptomatic Carotid Plaques. AB - BACKGROUND: Elevation of plasma high-density lipoprotein (HDL) cholesterol concentration reduces cardiovascular mortality and morbidity. HDLs have been shown to possess acute anti-inflammatory, antioxidant, and antithrombotic properties. We hypothesize that HDL therapy can acutely alter local and systemic manifestations of plaque instability. METHODS: Forty patients with early symptomatic carotid disease were randomized to either receive reconstituted HDL (rHDL) 40 mg/kg (n = 20) or placebo (n = 20). Carotid endarterectomies were performed 24 hr later. Plaques were obtained intraoperatively and used for measurement of thrombomodulatory genes expression. Plasma samples were collected before the infusion, 24 and 48 hr later to measure changes in systemic markers of plaque instability. RESULTS: No significant differences were noted in thrombomodulatory genes expression between the 2 groups. Systemic levels of tissue factor, matrix metalloproteinase 9 (MMP-9), and monocyte chemotactic factor-1 (MCP-1) were significantly reduced in the rHDL group. However, the effects on MMP-9 and MCP-1 were abolished in the immediate postoperative period. Although rHDL did not affect plasma interleukin-6 levels 24 hr following the infusion, it prevented the significant postoperative elevation seen in the placebo group. CONCLUSIONS: A single infusion of rHDL can acutely alter plasma biomarkers associated with plaque instability and cardiovascular morbidity. PMID- 26140944 TI - Patients' Views on Regional Anesthesia for Elective Unilateral Carotid Endarterectomy--A Prospective Cohort Study. AB - BACKGROUND: Carotid endarterectomy (CEA) can be performed under general anesthesia (GA) or locoregional anesthesia (LA). However, the patients' views on the choice between GA and LA are currently poorly understood. We aimed at identifying the preoperative patient information needs, their role in decision making, and influencing factors associated with LA and anxiety regarding surgery and anesthesia in CEA as a base for improving preoperative consultation and decision-making in the informed consent process. METHODS: Data were collected from consecutive patients undergoing unilateral elective CEA. Data on basic demographics, preoperative information needs, factors influencing decision-making concerning anesthesia technique, a Mini Mental State Examination (MMSE), a Visual Analog Scale (VAS), and the State-Trait Anxiety Inventory (STAI-T/S) were collected. RESULTS: A total of 59 patients were included in the study, 10 women and 49 men, with a median age of 71 years (interquartile range, 66-77 years). Fifty-four (92%) patients assessed the surgeons' given information as adequate. Older patients (>70 years, n = 31) had less self-conception of anxiety compared to younger patients (<=70 years, n = 28), 3% vs. 21%, P = 0.045. Males expressed less anxiety regarding "waking up during general anesthesia" compared to females (0% vs. 30%, P < 0.001). Anxiety about anesthesia and surgery as measured by VAS highly correlated with the STAI-S scores (Pearson correlation coefficient [CC], 0.45; 95% confidence interval [CI], 0.18-0.66, P < 0.001; CC, 0.47; 95% CI, 0.27 0.66, P < 0.001, respectively). Patients with a lower cognitive function (MMSE <=27, n = 20) had lower needs for preoperative medical information compared to patients with MMSE >27 (n = 36), 0% vs. 15%, P = 0.042. Two (3%) patients received GA because of their previous bad experience with LA. CONCLUSIONS: Younger and female patients may benefit from a more detailed and reassuring informed consent process. All institutions should use procedure-specific informed consent forms as they appear to be very adequate for the patient information needs. Nearly all patients are willing to undergo LA with the exception of those having had previous bad experience with LA for CEA. PMID- 26140945 TI - Popliteal Artery Pseudoaneurysm with Secondary Chronic Common Peroneal Nerve Neuropathy and Foot Drop after Total Knee Replacement. AB - Total knee replacements (TKRs) are performed to treat debilitating arthritis and are one of the most routinely performed surgical procedures in the United Kingdom. Complications of infection and deep vein thrombosis are well recognized and managed, whereas neurovascular injuries are rarely reported although should not be disregarded. We report on the case of a 72-year-old man who presented 5 weeks after a TKR with symptoms of a progressively worsening ipsilateral foot drop. A diagnosis of common peroneal nerve neuropathy secondary to the compressive effects of a popliteal pseudoaneurysm was made, and he underwent uneventful patch repair of the pseudoaneurysm. Unique to the literature is the chronicity of the foot drop, which still persisted at follow-up 6 weeks later. PMID- 26140946 TI - Results of the Gore Hybrid Vascular Graft in Challenging Aortic Branch Revascularization during Complex Aneurysm Repair. AB - BACKGROUND: Prolonged organ ischemia during complex aortic surgery is associated with increased morbidity and mortality. A novel hybrid graft (Gore Hybrid Vascular Graft) as composite of expanded polytetrafluorethylene vascular prosthesis that has a section reinforced with nitinol was investigated for feasibility and effectiveness during aortic repair. METHODS: Retrospective analysis of all consecutive patients treated with the hybrid vascular graft (HVG). Indication for graft implantation was surgeon's preference for branch revascularization in challenging aortic repair. RESULTS: Within 26 months, 25 Gore HVGs and 17 conventional grafts were implanted in 12 patients (age, 73 years; range, 33-79 years, 8 men). Eleven patients were treated for thoracoabdominal aortic aneurysms and one for aortoiliac aneurysm (elective = 6, urgent = 6). Nine visceral debranching procedures, 2 Crawford procedures, and 1 repair of an internal iliac aneurysm were performed. The distribution of HVG use was left renal artery = 10, right renal artery = 9, superior mesenteric artery = 4, celiac trunk = 1, and internal iliac artery = 1. Time to restore visceral blood flow during visceral debranching was 7 +/- 4 min for the Gore HVG vs. 12 +/ 6 min for conventional grafts (P < 0.01).Technical success was achieved in all cases. At 12 months of median follow-up, cumulative patency of the HVGs was 96%. CONCLUSIONS: The Gore HVG offers a new, simplified, and time-sparing technique for visceral anastomoses during complex aneurysm repair. However, long-term results are still lacking and need to be awaited. PMID- 26140947 TI - A national survey of gynecologists on current practice patterns for management of abnormal uterine bleeding in South Korea. AB - OBJECTIVE: To evaluate practice patterns of gynecologists in the management of abnormal uterine bleeding (AUB) in South Korea. METHODS: Between February 24 and March 12, 2014, a cross-sectional survey was performed through face-to-face interviews with 100 gynecologists selected through quota sampling reflecting regions and hospital types. Through the use of a questionnaire, the level of awareness and practice patterns regarding diagnosis and management of AUB were evaluated. RESULTS: Among 100 respondents, 60 reported that they had not previously heard of the International Federation of Gynecology and Obstetrics (FIGO) classification system. The standardization of AUB terminology was reported to be necessary or very necessary by 70 respondents. Pelvic ultrasonography would be used for diagnosis by 99 physicians. The most common first-line AUB treatment was combined oral contraceptives: 55 respondents would use them for heavy menstrual bleeding, 56 for intermenstrual bleeding, and 56 for polycystic ovary syndrome. Combined oral contraceptives were the preferred follow-up medication: 30 would use them for heavy menstrual bleeding, 24 for intermenstrual bleeding, and 52 for polycystic ovary syndrome. CONCLUSION: Despite implementation of the FIGO AUB classification system and guidelines, awareness and use among gynecologists in South Korea remains low. PMID- 26140948 TI - Hysteroscopic tubal electrocoagulation versus laparoscopic tubal ligation for patients with hydrosalpinges undergoing in vitro fertilization. AB - OBJECTIVE: To investigate the use and success rate of hysteroscopic tubal electrocoagulation for the treatment of hydrosalpinx-related infertility among patients undergoing in vitro fertilization (IVF) who have laparoscopic contraindications. METHODS: A prospective study was conducted among patients who had unilateral or bilateral hydrosalpinges identified on hysterosalpingography and vaginal ultrasonography, and who were undergoing IVF at a center in Cairo, Egypt, between January 1, 2013, and October 30, 2014. All patients who had contraindications for laparoscopy were scheduled for hysteroscopic tubal electrocoagulation (group 1); the other patients underwent laparoscopic tubal ligation (group 2). For all patients, hysterosalpingography was performed 3 months after their procedure to evaluate proximal tubal occlusion. RESULTS: Among 85 enrolled patients, 22 underwent hysteroscopic tubal electrocoagulation and 63 underwent laparoscopic tubal ligation. The procedure was successful in terms of tubal occlusion for 25 (93%) of 27 hydrosalpinges in group 1, and 78 (96%) of 81 hydrosalpinges in group 2 (P=0.597). No intraoperative or postoperative complications were reported. CONCLUSION: Hysteroscopic tubal electrocoagulation was found to be a successful treatment for hydrosalpinges before IVF when laparoscopy is contraindicated. PMID- 26140949 TI - "In rape cases we can use this pill": a multimethods assessment of emergency contraception knowledge, access, and needs on the Thailand-Burma border. AB - OBJECTIVES: To evaluate availability, service delivery, and barriers to access to emergency contraceptive pills (ECPs) along the Thailand-Burma border. METHODS: From June 2010 to May 2011 we undertook a multimethods qualitative assessment among cross-border populations, migrants, and refugees. We conducted 46 key informant interviews with representatives from 25 organizations, 18 focus group discussions with migrant adults, migrant adolescents, and healthcare workers, and a service mapping exercise with 22 stakeholders. RESULTS: We found low use of ECPs among the target populations. Structural barriers and lack of evidence-based reproductive health protocols, education, and information restrict access to the limited family planning resources available in this region. Misinformation about ECPs was widespread among health workers and organizational policies were often non-evidence based. CONCLUSION: Potential policy and program interventions to improve access to ECPs along the Thailand-Burma border include integrating evidence-based practices into community efforts, expanding training opportunities for health workers, and improving communication and coordination among organizations serving populations on both sides of the border. PMID- 26140950 TI - 7keto-stigmasterol and 7keto-cholesterol induce differential proteome changes to intestinal epitelial (Caco-2) cells. AB - Recent studies have expanded the appreciation of the roles of oxysterols triggering inflammatory, immune cytotoxic and apoptotic processes, but have not been considered for proteome analysis. A comparative proteomic study in intestinal epithelial cell cultures incubated (60 MUM/24 h) with 7keto cholesterol or 7keto-stigmasterol was performed. The influence of both compounds was studied following the nLC-TripleTOF analysis. Findings were compared to results for control cultures. In the principal component analysis (PCA) of proteome patterns, two components were extracted accounting for 99.8% of the variance in the protein expression. PCA analysis clearly discriminated between the perturbations in the proteome of cell cultures incubated with 7keto cholesterol and 7keto-stigmasterol. These proteins participate in mitochondrial function, lipid homeostasis, inflammation and immunity and cell proliferation. Remarkable differences between proteome patterns in cell cultures exposed to 7keto-cholesterol and 7keto-stigmasterol affect macrophage migration inhibitory factor, apolipoprotein E, Bcl-2-associated transcription factor and cellular retinoic acid-binding protein. Besides, exposure to 7keto-stigmasterol increased the concentration of ubiquitin-conjugating enzyme E2 and the mitochondrial superoxide dismutase protein. Such findings raise new questions about safety studies and the regulatory potential of oxysterols in the differentiation and function of intestinal and associated immune cells, their response to environmental stimuli and impairment of absorption processes. PMID- 26140951 TI - In vitro antifungal activity of allyl isothiocyanate (AITC) against Aspergillus parasiticus and Penicillium expansum and evaluation of the AITC estimated daily intake. AB - Isothiocyanates (ITCs) are natural compounds derived from cruciferous vegetables produced by enzymatic conversion of metabolites called glucosinolates. They are potentially useful antimicrobial compounds for food applications have been shown to be promising agents against cancer in human cell culture, animal models, and in epidemiological studies. In this study, the antifungal activity of the allyl isothiocyanate (AITC) was evaluated on two mycotoxigenic fungi as Aspergillus parasiticus and Penicillium expnsum, aflatoxins (AFs) and patulin (PAT) producers, employing an assay on solid medium. Also an approximation of the risk evaluation associated to the intake of food treated with the AITC to reduce the risk of fungi spoilage has been evaluated. On solid medium and after 20 days incubation the strain of Penicillium expansum was inhibited with AITC quantities highest than 50 mg, whereas the strain of A. parasiticus was sensible to AITC doses highest than 5 mg. The analysis of the risk assessment associated to the intake of several food classes treated with the bioactive compound AITC to prevent fungi spoilage evidenced that this product can be considered as safe due that the estimated daily intakes (EDIs) are always lower than the AITC Admissible Daily intake (ADI). PMID- 26140952 TI - RIFM fragrance ingredient safety assessment, (2E,6Z)-Nona-2,6-dien-1-ol, CAS registry number 28069-72-9. PMID- 26140953 TI - RIFM fragrance ingredient safety assessment, (Z)-2-penten-1-ol, CAS Registry Number 1576-95-0. PMID- 26140954 TI - Changes in end-tidal CO2 could predict fluid responsiveness in the passive leg raising test but not in the mini-fluid challenge test: A prospective and observational study. AB - OBJECTIVE: The objective is to explore the value of end-tidal carbon dioxide (ETCO2) in replacing cardiac index for evaluating fluid responsiveness during the passive leg raising (PLR) test and mini-fluid challenge (mini-FC). METHODS: Patients experiencing septic shock and who were on mechanical ventilation in an intensive care unit were divided into responder and nonresponder groups according to whether their cardiac index increased by more than 10% after the FC. Before and after those tests, the changes in ETCO2, central venous pressure, heart rate, mean arterial pressure, pulse pressure, and cardiac output were recorded. RESULTS: Of the 48 patients in the study, 34 had fluid responsiveness according to the changes in cardiac output or stroke volume. The DeltaCI and DeltaETCO2 in the responder group were larger than the changes in the nonresponder group during the PLR test (1.1 +/- 0.7 vs 0.2 +/- 0.4 L/min per square meter, 3.0 +/- 3.0 vs 0.5 +/- 2.5 mm Hg; P < .05) but not during mini-FC. DeltaETCO2 greater than or equal to 5% during the PLR test predicted fluid responsiveness with 93.4% specificity and 75.8% sensitivity in a receiver operating characteristic curve. The area under the curve was 0.849 (95% confidence interval, 0.739-0.930). DeltaETCO2 greater than or equal to 3% during the mini-FC predicted fluid responsiveness with 93.4% specificity and 33.3% sensitivity in a receiver operating characteristic curve, and the area under the curve was 0.781 (95% confidence interval, 0.646-0.915). CONCLUSIONS: The changes in ETCO2 may predict fluid responsiveness during the PLR test in patients with septic shock, but similar results were not found with the mini-FC. PMID- 26140955 TI - Elevation of red blood cell distribution width during hospitalization predicts mortality in patients with acute decompensated heart failure. AB - BACKGROUND: Increased red blood cell distribution width (RDW) is associated with adverse outcomes in heart failure. In the present study, we assessed the association between changes in RDW values during hospitalization and long-term prognosis in patients with acute decompensated heart failure (ADHF). METHODS: We measured the RDW value in 229 consecutive patients with ADHF. Blood samples were obtained at the time of hospital admission and at discharge. Changes in RDW were calculated as the mean difference between RDW values on admission and those at the time of hospital discharge. RESULTS: Patients were followed up for a median of 692 days. A Kaplan-Meier survival analysis demonstrated that patients whose RDW levels increased during hospitalization had significantly higher all-cause and cardiac-based mortality following heart failure than did patients whose RDW levels decreased during hospitalization. A multivariate Cox regression analysis revealed that change in RDW values during hospitalization, but not the values of RDW and hemoglobin on admission, was independently correlated with all-cause and cardiac-based mortality after adjusting for other risk factors in patients with ADHF. CONCLUSIONS: These data document that the change in RDW values during hospitalization independently predicts poor outcomes in patients with ADHF. Continuous follow-up of RDW values could provide useful information for long-term prognosis after heart failure. PMID- 26140956 TI - Machine Learning Approach to Optimizing Combined Stimulation and Medication Therapies for Parkinson's Disease. AB - BACKGROUND: Deep brain stimulation (DBS) of the subthalamic region is an established therapy for advanced Parkinson's disease (PD). However, patients often require time-intensive post-operative management to balance their coupled stimulation and medication treatments. Given the large and complex parameter space associated with this task, we propose that clinical decision support systems (CDSS) based on machine learning algorithms could assist in treatment optimization. OBJECTIVE: Develop a proof-of-concept implementation of a CDSS that incorporates patient-specific details on both stimulation and medication. METHODS: Clinical data from 10 patients, and 89 post-DBS surgery visits, were used to create a prototype CDSS. The system was designed to provide three key functions: (1) information retrieval; (2) visualization of treatment, and; (3) recommendation on expected effective stimulation and drug dosages, based on three machine learning methods that included support vector machines, Naive Bayes, and random forest. RESULTS: Measures of medication dosages, time factors, and symptom specific pre-operative response to levodopa were significantly correlated with post-operative outcomes (P < 0.05) and their effect on outcomes was of similar magnitude to that of DBS. Using those results, the combined machine learning algorithms were able to accurately predict 86% (12/14) of the motor improvement scores at one year after surgery. CONCLUSIONS: Using patient-specific details, an appropriately parameterized CDSS could help select theoretically optimal DBS parameter settings and medication dosages that have potential to improve the clinical management of PD patients. PMID- 26140957 TI - The Effect of Cerebellar Degeneration on Human Sensori-motor Plasticity. AB - BACKGROUND: Plasticity of the primary motor cortex (M1) has a critical role in motor control and learning. The cerebellum facilitates these functions using sensory feedback. OBJECTIVE: We investigated how cerebellar degeneration influences the plasticity of the M1 by using PAS (paired associative stimulation) technique. PAS involves repeated pairs of electrical stimuli to the median nerve and transcranial magnetic stimulation (TMS) of the motor cortex. If the interval between peripheral and TMS stimulation is around 21-25 ms, corticospinal excitability is increased via a long term potentiation (LTP)-like effect within M1. Our aims were: (i) to explore the presence of a time-specific influence of cerebellar degeneration on human associative plasticity; (ii) to evaluate the role played by somatosensory pathway on cerebellar modulation of sensory-motor plasticity. METHODS: We studied 10 patients with pure cerebellar atrophy and 10 age-matched healthy subjects. Motor-evoked-potentials amplitudes, short-afferent inhibition (SAI), motor thresholds, I/O curves, somatosensory-evoked-potential (SEP) were measured before, just after and 30 min after PAS at ISIs (interstimulus intervals) of 21.5 and 25 ms. RESULTS: Cerebellar patients show a selective lack of LTP-like effect induced by PAS25 ms, but not at 21.5 ms. SAI was overall not truly modulated by PAS but clearly differed between cerebellar patients and healthy subjects for ISIs around 25 ms (+6 ms and +8 ms) (P < 0.01). SEPs showed the amplitude of P25 wave was markedly reduced in patients with a more severe clinical and radiological impairment of cerebellum. CONCLUSIONS: Cerebellar patients have an altered capability of cerebellar filtering or processing of time-specific incoming sensory volleys, influencing the plasticity of M1. PMID- 26140958 TI - Dyslipidemia patterns are differentially associated with dietary factors. AB - BACKGROUND AND AIMS: Dyslipidemia, a strong predictor of cardiovascular diseases, is prevalent among Korean adults, but little is known about the associations between overall lipid profiles and dietary factors. We identified dyslipidemia patterns among lipid indicators and examined dietary factors associated with dyslipidemia patterns in Korean adults. METHODS: Subjects in this cross-sectional study were recruited from the Family Medicine Division or the Health Examination Center of the general hospital in Seoul between 2010 and 2012. Measurements of biochemical and dietary variables repeated three times were collected from a total of 138 subjects at 3- to 4-month intervals when the subjects visited the hospital. Dietary intake data were obtained using 24-h recalls. In order to estimate typical values for biochemical and dietary variables, the averages of repeated measures for each subject were calculated. To identify dyslipidemia patterns, factor analysis was used based on total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), triglycerides (TG), and high-density lipoprotein cholesterol (HDLC). RESULTS: Two dyslipidemia patterns, (1) TC & LDLC and (2) TG & HDLC, were identified. Dietary fat and cholesterol intakes were positively associated with the TC & LDLC pattern score, but not associated with the TG & HDLC pattern score. The TG & HDLC pattern was significantly associated with low intakes of calcium, potassium, milk and dairy products. CONCLUSIONS: Two dyslipidemia patterns were associated with dietary factors in Korean adults. Further studies should investigate specific dietary recommendations according to lipid profiles in the prevention and management of dyslipidemia in Korea. PMID- 26140959 TI - Protein sequence conservation and stable molecular evolution reveals influenza virus nucleoprotein as a universal druggable target. AB - The high mutation rate in influenza virus genome and appearance of drug resistance calls for a constant effort to identify alternate drug targets and develop new antiviral strategies. The internal proteins of the virus can be exploited as a potential target for therapeutic interventions. Among these, the nucleoprotein (NP) is the most abundant protein that provides structural and functional support to the viral replication machinery. The current study aims at analysis of protein sequence polymorphism patterns, degree of molecular evolution and sequence conservation as a function of potential druggability of nucleoprotein. We analyzed a universal set of amino acid sequences, (n=22,000) and, in order to identify and correlate the functionally conserved, druggable regions across different parameters, classified them on the basis of host organism, strain type and continental region of sample isolation. The results indicated that around 95% of the sequence length was conserved, with at least 7 regions conserved across the protein among various classes. Moreover, the highly variable regions, though very limited in number, were found to be positively selected indicating, thereby, the high degree of protein stability against various hosts and spatio-temporal references. Furthermore, on mapping the conserved regions on the protein, 7 drug binding pockets in the functionally important regions of the protein were revealed. The results, therefore, collectively indicate that nucleoprotein is a highly conserved and stable viral protein that can potentially be exploited for development of broadly effective antiviral strategies. PMID- 26140960 TI - Spatial genetic structure and restricted gene flow in bed bugs (Cimex lectularius) populations in France. AB - Bed bugs (Cimex lectularius) are resurgent blood-sucking ectoparasites that are currently increasing at a rapid rate, particularly in industrialized countries, such as France. Despite the rapid spread of bed bugs, there is a lack of knowledge concerning the population structure and gene flow among C. lectularius populations in France. To fill this gap, a genetic study was conducted using 183 C. lectularius from 14 populations of bed bugs collected in a hotel and in individual apartments in the French Riviera and in the Saint Ouen suburb of Paris. The samples were genotyped using an isolated set of six polymorphic microsatellite loci, including five new loci which were newly isolated and chosen based on prior successful amplification, and one previously described loci (bb15b). The low genetic diversity observed in the samples (of one to five alleles) suggested that most of prospected populations were established by only a few individuals, possibly from a single mated female. The overall genetic differentiation was high and statistically significant (FST=0.556, p<0.0001). Pairwise analysis of the populations indicated significant genetic differentiation for 24 out of the 45 (53%) population pairs associated with FST, ranging from 0.0042 to 0.862. No obvious relationship between the level of genetic differentiation and the geographic distance was observed when considering all samples. Analysis with Structure software identified nine distinct genetic clusters within the dataset. These preliminary results help to elucidate the genetic structure and gene flow of C. lectularius populations in France; however, the available information should be expanded in further studies. PMID- 26140962 TI - The Components of Smile Design: New York University Smile Evaluation Form Revisited, Update 2015. AB - This article updates a simple checklist of foundational knowledge in aesthetic dental concepts that allows clinicians to organize their thoughts, to record the concerns of the patient, and to map out those improvements that must be addressed. This adjunct is called a Smile Evaluation Form. Along with other adjuncts such as radiographs, study casts, and diagnostic wax-ups, the Smile Evaluation Form allows clinicians to form a conceptual visualization of the expected end point. It provides a checklist for discussions with other disciplines in the team, to provide a logical sequence of treatment with a mutually agreed-on end point. PMID- 26140961 TI - Design, synthesis and antiproliferative activities of novel benzamides derivatives as HDAC inhibitors. AB - Guided by the principle of nonclassical electronic isosterism and structural optimization, a series of novel HDAC inhibitors bearing a bicyclic heterocycle moiety were designed and synthesized based on the lead compound of MS-275. All the prepared compounds were evaluated for their in vitro antiproliferative activities against HCT-116, MCF-7 and A549 human cancer cell lines, all compounds exerted excellent antitumor activities. Moreover, the compound 4a exhibited an acceptable pharmacokinetic profile with bio-availability in rat of 76% and could be considered as a candidate compound for further development. PMID- 26140963 TI - An Aesthetic and Functional Rehabilitation: A Case Study. AB - This article describes a multidisciplinary approach to a functional and aesthetic rehabilitation. In this case study, we successfully corrected an anterior open bite and an exaggerated curve of Spee using restorative modalities while still maintaining a highly aesthetic outcome. The maxillary anterior teeth no longer appear to have a disproportional width/length ratio and are now in harmony with the mandibular veneers. Posterior function was re-established, mostly with implant-retained crowns. Occlusal harmony and stability are maintained through cuspid guidance and anterior disclusion. Proper selection of final restorative materials is imperative for the long-term survival of the restorations. PMID- 26140965 TI - Restoration of the Dentition in a Patient with a History of Non-Hodgkin Lymphoma and Gastroesophageal Reflux Disease. AB - Patients are concerned about dental disease and their appearance. Clinicians often must decide not only the type of restoration, but also the type of material for restoration that will provide aesthetics and longevity. A modern practitioner should know the pros and cons of different types of crowns and veneers. They are also responsible to provide treatment for patients with complicated medical histories. Risk assessments include current conditions, risks of recurrence, and suggestions for maintenance of restorations, as well as guidelines to promote the future health and well-being of the patient. PMID- 26140964 TI - Replacement of Old Porcelain-Fused-to-Metal Crowns and Smile Rejuvenation Using All-Ceramic Restorations. AB - This case report points out the previous restorative breakdown of tooth #8. An interdisciplinary approach had to be applied to prepare the final treatment plan. All factors were taken into account when choosing the type of restorations and materials in this case. The ultimate treatment is presented with the final result. The objectives were to clinically assess patient's current chief complaint, address her aesthetic needs, apply an interdisciplinary approach, deliver treatment of utmost quality, and maintain oral health. PMID- 26140966 TI - Restoration of Fluorosis Stained Teeth: A Case Study. AB - Dental fluorosis manifests by too much ingestion of fluoride resulting in disturbances in enamel mineralization. The result is intrinsic discolorations in the maxillary and mandibular teeth with a poor esthetic appearance. In challenging cases, an esthetic result may be achieved only by a combination of techniques. This case report demonstrates a combination of modalities used to treat a patient presenting with atypical staining as a result of high-level exposure to ingested fluoride present in the drinking water as a child. Conservative treatment consisted of a combination of in-office bleaching to reduce the discoloration and porcelain veneers to create an esthetic result. PMID- 26140967 TI - Comprehensive Risk-Based Diagnostically Driven Treatment Planning: Developing Sequentially Generated Treatment. AB - The clinical example presented in this article demonstrates a risk-based, diagnostically driven treatment planning approach by focusing on 4 key categories: periodontal, biomechanical, functional, dentofacial. In addition, our unique approach allowed the comprehensive clinical management of a patient with complex restorative needs. A full-mouth rehabilitation was completed sequentially without sacrificing the amount of dentistry necessary to restore health, comfort, function, and esthetics. The result exceeded the patient's expectation and was made financially possible by extending treatment over numerous years. PMID- 26140968 TI - Full Mouth Rehabilitation Determined by Anterior Tooth Position. AB - When patients seek cosmetic dentistry, their main concern is how their new smile is going to appear. In trying to achieve a patient's desire for a more beautiful smile, a careful and comprehensive analysis must be completed to insure the desired outcome is achievable and will function for many years to come. The clinician's primary goal is to restore the patient's dentition to ideal form and function. Full mouth rehabilitations need to be done in a systematic way to ensure all the parameters of an esthetic and functional outcome are achieved. PMID- 26140969 TI - Proportional Smile Design: Using the Recurring Esthetic Dental Proportion to Correlate the Widths and Lengths of the Maxillary Anterior Teeth with the Size of the Face. AB - Proportional smile design is a useful tool for evaluating and designing smiles that are in harmony with the face. Although not always observed in nature, the recurring esthetic dental proportion is preferred by dentists surveyed to the width proportions observed in nature with normal-length teeth. The width/length ratio of the central incisor is a key determinant in providing a smile that is pleasing to dentists. Using the desired tooth length while maintaining the preferred 78% width/length ratio of the central incisor in conjunction with the recommended recurring esthetic dental proportion is a good method for designing a smile balanced with the face. PMID- 26140970 TI - Cosmetic Makeover Ensuring Patient Input in a Multidisciplinary Treatment. AB - A cosmetic smile makeover has become a sought after procedure in our esthetically driven society. To promote patient satisfaction with treatment outcomes, all parties involved, including the patient, must be aware of the results that can be achieved and what it will require to achieve them. Although treatment can be redone, it cannot be undone. Therefore, much patient input must be solicited and considered before beginning treatment and before the final restorations are cemented. This article provides a treatment sequence that minimizes the possibility of an unhappy patient. PMID- 26140971 TI - Esthetic Correction of Orthodontically Transposed Teeth with Veneers and Laser Periodontal Modification. AB - Missing teeth in the esthetic zone, whether congenital or as a result of other factors, present difficult choices in clinical management. The missing teeth can be replaced by surgical or restorative intervention but are often treated orthodontically. These repositioned teeth often lead to an unaesthetic result because of differences in morphology, color, and particularly in gingival architecture. This article describes the use of multiple lasers for periodontal modification and feldspathic porcelain veneers to achieve a highly esthetic result. PMID- 26140972 TI - Simple Case Treatment Planning: Diastema Closure. AB - This article demonstrates the use of a smile evaluation form as an adjunct in arriving at diagnosis and developing a treatment plan for a patient desiring Diastema closure. It also shows the importance of the diagnostic wax-up for temporization and visualization of case outcome. The case also demonstrates the use of soft tissue lasers to create a gingival harmony that enhanced the resulting esthetics. Feldspathic porcelain was used for the final restorations because they provide optimal esthetics and translucency. PMID- 26140973 TI - Management of an Adult with Class III Malocclusion, Gummy Smile, and Spaced Dentition. AB - This case report presents an interdisciplinary approach to achieve functioning occlusion and an aesthetically pleasing smile. This patient's concerns were spacing between upper front teeth and a gummy smile. The case was evaluated, and treatment was planned using a multidisciplinary approach. The patient rejected the option of orthognathic surgery to correct a skeletal problem. Treatment included orthodontics, osteoplasty, gingivoplasty, and porcelain veneer restorations to achieve the desired aesthetic result. Comprehensive orthodontics resulted in a functionally stable occlusion. Space distribution between maxillary anterior teeth with adequate overjet and overbite relationships allowed for conservative preparation to receive porcelain veneer restorations. PMID- 26140974 TI - Esthetic Smile Design: Limited Orthodontic Therapy to Position Teeth for Minimally Invasive Veneer Preparation. AB - The standards of dentistry are being elevated, with a greater emphasis being placed on esthetics along with functionality. Minimally invasive dentistry has become an essential component in creating restorations that are functional and have increased longevity. In the case discussed in this article, the patient underwent 9 months of orthodontic therapy to correct her improper overbite and overjet, and the spacing of her dentition so the teeth could be positioned for future minimally invasive restorations. Orthodontic therapy was paramount in positioning the teeth so that the future restorations would have ideal axial inclinations and be as minimally invasive as possible. PMID- 26140975 TI - The Interplay of Orthodontics, Periodontics, and Restorative Dentistry to Achieve Aesthetic and Functional Success. AB - Previously dentists focused on repair and maintenance of function. However, the emphasis of many patients and dentists is now on esthetics. Often there is a need for the disciplines of orthodontics, periodontics, restorative dentistry, and maxillofacial surgery to work together in order to achieve optimum results. Currently the sequencing planning process begins with esthetics and then function, structure, and ultimately biology. PMID- 26140976 TI - Treatment of the Patient with Gummy Smile in Conjunction with Digital Smile Approach. AB - Gummy smile cases are always esthetically demanding cases. This article presents a case treated with an interdisciplinary treatment approach and Digital Smile Approach (DSA) using Keynote (DSA), to predictably achieve an esthetic outcome for a patient with gummy smile. The importance of using questionnaires and checklists to facilitate the gathering of diagnostic data cannot be overemphasized. The acquired data must then be transferred to the design of the final restorations. The use of digital smile design has emerged as a powerful tool in cosmetic dentistry to help both practitioner and patient visualize the final outcome. PMID- 26140977 TI - Interdisciplinary Sequencing of Aesthetic Treatment. AB - This article describes the concepts of treating a complex aesthetic interdisciplinary case in a traditional approach. PMID- 26140978 TI - Restoration of the Anterior Segment in a Cleft Palate in Conjunction with Surgically Facilitated Orthodontic Therapy: An Interdisciplinary Approach. AB - A 26-year-old woman was referred to a periodontal surgical practice for concerns related to gingival recession. After several consultations among the orthodontist, periodontist, and cosmetic/restorative dentist, she decided to have surgically facilitated orthodontic therapy as part of a collaborative, interdisciplinary treatment planning process to correct her constricted maxillary arch form, augment thin dentoalveolar facial bone, simultaneously with gaining root coverage as well as improving attached gingiva width and mucogingival thickness. As a consequence of changing the arch form, an improvement in the buccal corridor space was gained which optimized her smile display. PMID- 26140979 TI - Modern Concepts in Aesthetic Dentistry and Multidisciplined Reconstructive Grand Rounds. PMID- 26140980 TI - In vitro antitumor immune response induced by dendritic cells transduced with human livin alpha recombinant adenovirus. AB - Transduction with recombinant, replication-defective adenoviral (rAd) vectors encoding a transgene is an efficient method for gene transfer into human dendritic cells (DCs). Livin is a good candidate for cancer immunotherapy since it is overexpressed in most common human cancers, poorly expressed in most normal adult tissues. Two splicing variants of livin, designated livin alpha and livin beta, have been identified. In this study, we used human livin alpha recombinant adenovirus (rAd-hlivin alpha) to transduced DCs. We found that DCs transduced with rAd-hlivin alpha (rAd-hlivin alpha DCs) could effectively induce human livin alpha specific cytotoxic T lymphocytes (CTL) in vitro against various tumor cell lines. PMID- 26140981 TI - Molecular characterization of Helja, an extracellular jacalin-related protein from Helianthus annuus: Insights into the relationship of this protein with unconventionally secreted lectins. AB - Jacalin-related lectins (JRLs) encompass cytosolic, nuclear and vacuolar members displaying the jacalin domain in one or more copies or in combination with unrelated domains. Helianthus annuus jacalin (Helja) is a mannose-specific JRL previously identified in the apoplast of Helianthus annuus seedlings, and this protein has been proposed to follow unconventional secretion. Here, we describe the full-length Helja cDNA sequence, which presents a unique jacalin domain (merolectin) and the absence of a signal peptide, confirming that the protein cannot follow the classical ER-dependent secretory pathway. Helja mRNA is present in seeds, cotyledons, roots and hypocotyls, but no transcripts were detected in the leaves. Searches for sequence similarity showed that Helja is barely similar to other JRLs present in H. annuus databases and less than 45% identical to other monocot or dicot JRLs. Strikingly, most of the merolectins recovered through data mining using Helja as a query were predicted as apoplastic, although most of these proteins lack the signal peptide required for classical secretion. Thus, Helja is the first bait identified to recover putative unconventionally secreted lectins. Because the recovered JRLs are widely distributed among the plant kingdom, an as yet unknown role for jacalin lectins in the apoplast is emerging. PMID- 26140982 TI - Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint. AB - We report an extremely rare case of primary clear cell carcinoma (CCC), not otherwise specified (NOS) of the nasal cavity. An 80-year-old woman was referred to our hospital with left nasal obstruction caused by a nasal cavity tumor. The tumor was resected completely with lateral rhinotomy approach. Histopathological examination revealed CCC. CCC metastasis from renal cell carcinoma (RCC), which is at the top of differential diagnosis, was ruled out by the absence of renal tumor at computed tomography (CT). Also, immunohistochemical results of the specimen with vimentin negative and CK7 focally positive excluded the possibility of RCC metastasis. The patient is free from recurrence 1 year after the surgery, and there is no evidence of RCC. In this report histopathological characteristics, especially immunohistochemical properties of primary CCC, NOS of the nasal cavity are presented together with some clinical features of this rare tumor. Also, we refer to histopathogenesis of primary CCC of nasal cavity in relation to myoepithelial carcinoma. Histopathological discussion is further extended to include other CCC and CCC-resembling histologies to confirm the uniqueness of the present case. PMID- 26140983 TI - GRID and docking analyses reveal a molecular basis for flavonoid inhibition of Src family kinase activity. AB - Flavonoids reduce cardiovascular disease risk through anti-inflammatory, anti coagulant and anti-platelet actions. One key flavonoid inhibitory mechanism is blocking kinase activity that drives these processes. Flavonoids attenuate activities of kinases including phosphoinositide-3-kinase, Fyn, Lyn, Src, Syk, PKC, PIM1/2, ERK, JNK and PKA. X-ray crystallographic analyses of kinase flavonoid complexes show that flavonoid ring systems and their hydroxyl substitutions are important structural features for their binding to kinases. A clearer understanding of structural interactions of flavonoids with kinases is necessary to allow construction of more potent and selective counterparts. We examined flavonoid (quercetin, apigenin and catechin) interactions with Src family kinases (Lyn, Fyn and Hck) applying the Sybyl docking algorithm and GRID. A homology model (Lyn) was used in our analyses to demonstrate that high-quality predicted kinase structures are suitable for flavonoid computational studies. Our docking results revealed potential hydrogen bond contacts between flavonoid hydroxyls and kinase catalytic site residues. Identification of plausible contacts indicated that quercetin formed the most energetically stable interactions, apigenin lacked hydroxyl groups necessary for important contacts and the non-planar structure of catechin could not support predicted hydrogen bonding patterns. GRID analysis using a hydroxyl functional group supported docking results. Based on these findings, we predicted that quercetin would inhibit activities of Src family kinases with greater potency than apigenin and catechin. We validated this prediction using in vitro kinase assays. We conclude that our study can be used as a basis to construct virtual flavonoid interaction libraries to guide drug discovery using these compounds as molecular templates. PMID- 26140984 TI - Suppression of ornithine decarboxylase promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. AB - Ornithine decarboxylase (ODC) is the rate-limiting enzyme for polyamine biosynthesis. Suppression of ODC by its irreversible inhibitor, alpha difluoromethylornithine (DFMO), or by RNA interference through siRNA, enhanced osteogenic gene expression and alkaline phosphatase activity, and accelerated matrix mineralization of human bone marrow-derived mesenchymal stem cells (hBMSCs). Besides, adipogenic gene expression and lipid accumulation was attenuated, indicating that the enhanced osteogenesis was accompanied by down regulation of adipogenesis when ODC was suppressed. A decrease in the intracellular polyamine content of hBMSCs during osteogenic induction was observed, suggesting that the level of endogenous polyamines is regulated during differentiation of hBMSCs. This study elucidates the role of polyamine metabolism in the lineage commitment of stem cells and provides a potential new indication for DFMO as bone-stimulating drug. PMID- 26140985 TI - Nuclear versus cytosolic activity of the yeast Hog1 MAP kinase in response to osmotic and tunicamycin-induced ER stress. AB - We examined the physiological significance of the nuclear versus cytosolic localization of the MAPK Hog1p in the ability of yeast cells to cope with osmotic and ER (endoplasmic reticulum) stress. Our results indicate that nuclear import of Hog1p is not critical for osmoadaptation. Plasma membrane-anchored Hog1p is still able to induce increased expression of GPD1 and glycerol accumulation. This is a key osmoregulatory event, although a small production of the osmolyte coupled with the nuclear import of Hog1p is sufficient to provide osmoresistance. On the contrary, the nuclear activity of Hog1p is dispensable for ER stress adaptation. PMID- 26140986 TI - Dynamics, flexibility, and allostery in molecular chaperonins. AB - The chaperonins are a family of molecular chaperones present in all three kingdoms of life. They are classified into Group I and Group II. Group I consists of the bacterial variants (GroEL) and the eukaryotic ones from mitochondria and chloroplasts (Hsp60), while Group II consists of the archaeal (thermosomes) and eukaryotic cytosolic variants (CCT or TRiC). Both groups assemble into a dual ring structure, with each ring providing a protective folding chamber for nascent and denatured proteins. Their functional cycle is powered by ATP binding and hydrolysis, which drives a series of structural rearrangements that enable encapsulation and subsequent release of the substrate protein. Chaperonins have elaborate allosteric mechanisms to regulate their functional cycle. Long-range negative cooperativity between the two rings ensures alternation of the folding chambers. Positive intra-ring cooperativity, which facilitates concerted conformational transitions within the protein subunits of one ring, has only been demonstrated for Group I chaperonins. In this review, we describe our present understanding of the underlying mechanisms and the structure-function relationships in these complex protein systems with a particular focus on the structural dynamics, allostery, and associated conformational rearrangements. PMID- 26140987 TI - Cationic polyaspartamide-based nanocomplexes mediate siRNA entry and down regulation of the pro-inflammatory mediator high mobility group box 1 in airway epithelial cells. AB - High-mobility group box 1 (HMGB1) is a nonhistone protein secreted by airway epithelial cells in hyperinflammatory diseases such as asthma. In order to down regulate HMGB1 expression in airway epithelial cells, siRNA directed against HMGB1 was delivered through nanocomplexes based on a cationic copolymer of poly(N 2-hydroxyethyl)-d,l-aspartamide (PHEA) by using H441 cells. Two copolymers were used in these experiments bearing respectively spermine side chains (PHEA-Spm) and both spermine and PEG2000 chains (PHEA-PEG-Spm). PHEA-Spm and PHEA-PEG-Spm derivatives complexed dsDNA oligonucleotides with a w/w ratio of 1 and higher as shown by a gel retardation assay. PHEA-Spm and PHEA-PEG-Spm siRNA polyplexes were sized 350-650 nm and 100-400 nm respectively and ranged from negativity/neutrality (at 0.5 ratio) to positivity (at 5 ratio) as zeta potential. Polyplexes formed either at a ratio of 0.5 (partially complexing) or at the ratio of 5 (fully complexing) were tested in subsequent experiments. Epifluorescence revealed that nanocomplexes favored siRNA entry into H441 cells in comparison with naked siRNA. As determined by flow cytometry and a trypan blue assay, PHEA-Spm and PHEA-PEG-Spm allowed siRNA uptake in 42-47% and 30% of cells respectively, however only with PHEA-Spm at w/w ratio of 5 these percentages were significantly higher than those obtained with naked siRNA (20%). Naked siRNA or complexed scrambled siRNA did not exert any effect on HMGB1mRNA levels, whereas PHEA-Spm/siRNA at the w/w ratio of 5 down-regulated HMGB1 mRNA up to 58% of control levels (untransfected cells). PEGylated PHEA-Spm/siRNA nanocomplexes were able to down-regulate HMGB1 mRNA levels up to 61% of control cells. MTT assay revealed excellent biocompatibility of copolymer/siRNA polyplexes with cells. In conclusion, we have found optimal conditions for down-regulation of HMGB1 by siRNA delivery mediated by polyaminoacidic polymers in airway epithelial cells in the absence of cytotoxicity. Functional and in-vivo studies are warranted. PMID- 26140988 TI - Redo double-opposing Z-plasty is effective for correction of marginal velopharyngeal insufficiency. AB - OBJECTIVE: Double-opposing Z-plasty (DOZ) of the Furlow method has been successfully used for the correction of marginal velopharyngeal insufficiency (VPI) by reconstructing the levator muscle and lengthening the soft palate. For a recurrent or residual marginal VPI, it was questioned whether redo DOZ could be applied to correct the problem and minimize surgical morbidity. This study reported the outcome of the redo DOZ. MATERIALS AND METHODS: The DOZ procedure was the method of choice for marginal VPI in the authors' center. To evaluate the effectiveness of the redo operation, patients with cleft palate with or without cleft lip treated from 2005 to 2014 were reviewed. Inclusion criteria were non syndromic patients who underwent the second DOZ for the correction of marginal VPI. Clinical information, speech assessment, and nasopharyngoscopic findings were reviewed. RESULTS: The velopharyngeal function was improved from marginal to adequate in all 13 patients either subjectively or objectively. The resonance became normal in nine patients after the surgery, and the change was statistically significant. Preoperative audible nasal emission improved in four out of five patients. Complications were minor or transient including one patient with snoring. No patient complained of airway or sleep problems. CONCLUSION: Although the levator muscle sling might be disturbed by the redo DOZ procedure, the surgery was effective in correcting the residual VPI with low morbidity. PMID- 26140989 TI - Incorporation of electrochemical advanced oxidation processes in a multistage treatment system for sanitary landfill leachate. AB - The current study has proved the technical feasibility of including electrochemical advanced oxidation processes (EAOPs) in a multistage strategy for the remediation of a sanitary landfill leachate that embraced: (i) first biological treatment to remove the biodegradable organic fraction, oxidize ammonium and reduce alkalinity, (ii) coagulation of the bio-treated leachate to precipitate humic acids and particles, followed by separation of the clarified effluent, and (iii) oxidation of the resulting effluent by an EAOP to degrade the recalcitrant organic matter and increase its biodegradability so that a second biological process for removal of biodegradable organics and nitrogen content could be applied. The influence of current density on an UVA photoelectro-Fenton (PEF) process was firstly assessed. The oxidation ability of various EAOPs such as electro-Fenton (EF) with two distinct initial total dissolved iron concentrations ([TDI]0), PEF and solar PEF (SPEF) was further evaluated and these processes were compared with their analogous chemical ones. A detailed assessment of the two first treatment stages was made and the biodegradability enhancement during the SPEF process was determined by a Zahn-Wellens test to define the ideal organics oxidation state to stop the EAOP and apply the second biological treatment. The best current density was 200 mA cm(-2) for a PEF process using a BDD anode, [TDI]0 of 60 mg L(-1), pH 2.8 and 20 degrees C. The relative oxidation ability of EAOPs increased in the order EF with 12 mg [TDI]0 L(-1) < EF with 60 mg [TDI]0 L(-1) < PEF with 60 mg [TDI]0 L(-1) <= SPEF with 60 mg [TDI]0 L(-1), using the abovementioned conditions. While EF process was much superior to the Fenton one, the superiority of PEF over photo-Fenton was less evident and SPEF attained similar degradation to solar photo-Fenton. To provide a final dissolved organic carbon (DOC) of 163 mg L(-1) to fulfill the discharge limits into the environment after a second biological process, 6.2 kJ L(-1) UV energy and 36 kWh m(-3) electrical energy were consumed using SPEF with a BDD anode at 200 mA cm(-2), 60 mg [TDI]0 L(-1), pH 2.8 and 20 degrees C. PMID- 26140990 TI - Combination of UV absorbance and electron donating capacity to assess degradation of micropollutants and formation of bromate during ozonation of wastewater effluents. AB - In this study, the changes in UV absorbance at 254 nm (UVA254) and electron donating capacity (EDC) were investigated as surrogate indicators for assessing removal of micropollutants and bromate formation during ozonation of wastewater effluents. To measure the EDC, a novel method based on size exclusion chromatography followed by a post-column reaction was developed and calibrated against an existing electrochemical method. Low specific ozone doses led to a more efficient abatement of EDC than of UVA254. This was attributed to the abatement of phenolic moieties in the dissolved organic matter (DOM), which lose their EDC upon oxidation, but are partially transformed into quinones, which still absorb in the measured UV range. For higher specific ozone doses, the relative EDC abatement was lower than the relative UVA abatement, which can be explained by the oxidation of UV absorbing moieties (e.g. non-activated aromatic compounds), which contribute less to EDC. The abatement of the selected micropollutants (i.e., 17alpha-ethinylestradiol (EE2), carbamazepine (CBZ), atenolol (ATE), bezafibrate (BZF), ibuprofen (IBU), and p-chlorobenzoic acid (pCBA)) varied significantly depending on their reactivity with ozone in the examined specific ozone dose range of 0-1.45 mgO3/mgDOC. The decrease of EE2 and CBZ with high ozone reactivity was linearly proportional to the reduction of the relative residuals of UVA254 and EDC. The abatement of ATE, BZF, IBU, and pCBA with intermediate to low ozone reactivities was not significant in a first phase (UVA254/UVA254,0 = 1.00-0.70; EDC/EDC0 = 1.00-0.56) while their abatement was more efficient than the degradation of the relative residual UVA254 and much more noticeable than the degradation of the relative residual EDC in a second phase (UVA254/UVA254,0 = 0.70-0.25; EDC/EDC0 = 0.56-0.25) because the partially destroyed UV absorbing and electron donating DOM moieties become recalcitrant to ozone attack. Bromate formation was pronounced for specific ozone doses >0.25 mgO3/mgDOC. At these ozone doses, the residual DOM competes less with bromide for ozone as the electron-rich DOM moieties are almost completely degraded. Overall, these results imply that a combination of the relative residual UVA254 and EDC more truly reflects the intrinsic reactivity of DOM associated with the removal of micropollutants and bromate formation than the single use of the UV absorbance based surrogate indicators. PMID- 26140991 TI - From creativity to perception: The conditions of possibility for a true biology. AB - The phenomenologist Renaud Barbaras defends an alternative conception of life against the well-known proposals that view life as self-preserving or seeking to replicate its own means of replication in the form of repetition instead of creation or accomplishment as Barbaras proposes. Indeed, he criticizes the reductive nature of scientific inquiry which tries to define life solely on the basis of the internal constraints, which leads to an impossible true biology. Barbaras' conception is rooted in Husserl and Merleau-Ponty who conceives perception as a subjective act by which the subject enters a relationship with the world. This leads the subject to overcome the Husserlian resources to reach the originary link of the organism with itself and the exteriority. This originary link is expressed in the ambiguity of the verb "to live" in French which designates both being alive and the experience of something. According to Barbaras, desire as life is the infinite exploration of the external world. The movement is due to the nature of perception itself, inasmuch as infinite exploration is in the very nature of the perceptive movement itself, which opens an unfulfillable absence within the exterior world. Then, life as desire is the desire of the world. Life is accomplished only as an unfolding of the world. Then, Barbaras' model seems to preserve the unity of the organism that allows the phenomenal level or the lived experience, the indefinite engagement with exteriority and the positivity of absence created by the movement through its activity. From this, we propose to complement Barbaras' insights on negativity and the expressions of desire with our approach concerning three main points. In the first place, we interpret Barbaras' notion of life as accomplishment within the Whiteheadian framework of creativity, thereby granting the thermodynamic reality of living systems. Secondly, we clarify the meaning of the couple movement/manifestation so that these concepts are as fully applicable to the plant world as Barbaras accords to the animal world. Finally, our theoretical approach uses category theory to give scalability to the model. PMID- 26140992 TI - Linking structural features from mitochondrial and bacterial F-type ATP synthases to their distinct mechanisms of ATPase inhibition. AB - ATP synthases are molecular motors, which synthesize ATP, the ubiquitous energy source in all living cells. They use an electrochemical gradient to drive a rotation in the membrane embedded Fo domain, namely the c-ring, causing a conformational change in the soluble F1 domain which leads to the catalytic event. In the opposite fashion, they can also hydrolyse ATP to maintain the ion gradient across the membrane. To prevent wasteful ATP hydrolysis, bacteria and mammals have developed peculiar mechanistic features in addition to a common one, namely MgADP inhibition. Here I discuss the distinct ATPase inhibition mechanism in mitochondrial (IF1) and bacterial (subunits epsilon and zeta) F-type ATP synthases, based on available structural, biophysical and biochemical data. PMID- 26140993 TI - The universal numbers. From Biology to Physics. AB - I will explain how the mathematicians have discovered the universal numbers, or abstract computer, and I will explain some abstract biology, mainly self reproduction and embryogenesis. Then I will explain how and why, and in which sense, some of those numbers can dream and why their dreams can glue together and must, when we assume computationalism in cognitive science, generate a phenomenological physics, as part of a larger phenomenological theology (in the sense of the greek theologians). The title should have been "From Biology to Physics, through the Phenomenological Theology of the Universal Numbers", if that was not too long for a title. The theology will consist mainly, like in some (neo)platonist greek-indian-chinese tradition, in the truth about numbers' relative relations, with each others, and with themselves. The main difference between Aristotle and Plato is that Aristotle (especially in its common and modern christian interpretation) makes reality WYSIWYG (What you see is what you get: reality is what we observe, measure, i.e. the natural material physical science) where for Plato and the (rational) mystics, what we see might be only the shadow or the border of something else, which might be non physical (mathematical, arithmetical, theological, ...). Since Godel, we know that Truth, even just the Arithmetical Truth, is vastly bigger than what the machine can rationally justify. Yet, with Church's thesis, and the mechanizability of the diagonalizations involved, machines can apprehend this and can justify their limitations, and get some sense of what might be true beyond what they can prove or justify rationally. Indeed, the incompleteness phenomenon introduces a gap between what is provable by some machine and what is true about that machine, and, as Godel saw already in 1931, the existence of that gap is accessible to the machine itself, once it is has enough provability abilities. Incompleteness separates truth and provable, and machines can justify this in some way. More importantly incompleteness entails the distinction between many intensional variants of provability. For example, the absence of reflexion (beweisbar(?A?) -> A with beweisbar being Godel's provability predicate) makes it impossible for the machine's provability to obey the axioms usually taken for a theory of knowledge. The most important consequence of this in the machine's possible phenomenology is that it provides sense, indeed arithmetical sense, to intensional variants of provability, like the logics of provability-and-truth, which at the propositional level can be mirrored by the logic of provable-and-true statements (beweisbar(?A?) ? A). It is incompleteness which makes this logic different from the logic of provability. Other variants, like provable-and-consistent, or provable-and-consistent-and-true, appears in the same way, and inherits the incompleteness splitting, unlike beweisbar(?A?) ? A. I will recall thought experience which motivates the use of those intensional variants to associate a knower and an observer in some canonical way to the machines or the numbers. We will in this way get an abstract and phenomenological theology of a machine M through the true logics of their true self-referential abilities (even if not provable, or knowable, by the machine itself), in those different intensional senses. Cognitive science and theoretical physics motivate the study of those logics with the arithmetical interpretation of the atomic sentences restricted to the "verifiable" (Sigma1) sentences, which is the way to study the theology of the computationalist machine. This provides a logic of the observable, as expected by the Universal Dovetailer Argument, which will be recalled briefly, and which can lead to a comparison of the machine's logic of physics with the empirical logic of the physicists (like quantum logic). This leads also to a series of open problems. PMID- 26140994 TI - "Menaced Rationality": Husserl and Merleau-Ponty on the Crisis and Promise of Science. AB - In this paper I provide an overview of Husserl's and Merleau-Ponty's phenomenological critique of science, and suggest that such a critique is not only necessary in order to resolve an aporia that is otherwise apparently endemic to science, but that such a critique may also offer resources for productively addressing related philosophical difficulties, particularly the relationship between ideality and materiality/"nature." Following Husserl and Merleau-Ponty, I maintain that only a phenomenologically grounded science can be consistently "scientific." PMID- 26140995 TI - Finding an information concept suited for a universal theory of information. AB - The view argued in this article is that if we want to define a universal concept of information covering subjective experiential and meaningful cognition - as well as intersubjective meaningful communication in nature, technology, society and life worlds - then the main problem is to decide, which epistemological, ontological and philosophy of science framework the concept of information should be based on and integrated in. All the ontological attempts to create objective concepts of information result in concepts that cannot encompass meaning and experience of embodied living and social systems. There is no conclusive evidence that the core of reality across nature, culture, life and mind is purely either mathematical, logical or of a computational nature. Therefore the core of the information concept should not only be based only on pure logical or mathematical rationality. We need to include interpretation, signification and meaning construction in our transdisciplinary framework for information as a basic aspect of reality alongside the physical, chemical and molecular biological. Dretske defines information as the content of new, true, meaningful, and understandable knowledge. According to this widely held definition information in a transdisciplinary theory cannot be 'objective', but has to be relativized in relation to the receiver's knowledge, as also proposed by Floridi. It is difficult to produce a quantitative statement independently of a qualitative analysis based on some sort of relation to the human condition as a semiotic animal. I therefore alternatively suggest to build information theories based on semiotics from the basic relations of embodied living systems meaningful cognition and communication. I agree with Peircean biosemiotics that all information must be part of real relational sign-processes manifesting as tokens. PMID- 26140996 TI - Doing the math: Calculating the role of evolution and enculturation in the origins of geometrical and mathematical reasoning. AB - In this paper I review broadly embodied, phenomenological and evolutionary conceptions of the origin of mathematics. I relate these conceptions to Husserl's work on the origins of geometry, and recent research into the notion of extended expertise and the role of enculturation as they relate to mathematical reasoning. I suggest that the concept of 'affordance space' - the (abstract) range of possibilities provided by any change in body or environment - is a useful construct in working out the contributions of evolution and enculturation to mathematical reasoning. PMID- 26140997 TI - Transmembrane signaling: A multiplex problem with converging solutions. PMID- 26140998 TI - Cell phenomenology: The first phenomenon. AB - As a broad academic discipline phenomenology may be summarized as the study from a first person point of view of what appears to subjective human conscious experience. As a historical philosophical movement phenomenology was often motivated by the belief that subjective human experience is the proper foundation of all philosophy. I explore phenomena from a broader evolutionary and physical point of view. I consider a phenomenon as the subjective consequence of a physical interaction with an individual organism. In physical terms, a phenomenon requires some form of detection or measurement. What is detected is determined by the organism, and is potentially functional for the organism as a self or subject. The concept of function has meaning only for living organisms. The classical human mind-body problem is an ill-defined complicated case of the more general epistemic subject-object problem, which at the origin of life I reduce to the primitive symbol-matter problem. I argue that the first memory-based self replicating unit, like a cell, is the most primitive case of a necessary symbol matter distinction. The first phenomena, which include all forms or sensing, detection, and measurement, require a subject-object distinction, called the epistemic cut. It is only because of such a subject-object distinction that populations of individual subjects can selectively adapt to their environment by heritable variations. This basic evolutionary process requires distinguishing the individual's subjective phenomena from the objective events of inexorable physical laws. PMID- 26140999 TI - Situated phenomenology and biological systems: Eastern and Western synthesis. AB - Phenomenology was born with the mission to give foundations for science of experience and to open consciousness to scientific study. The influence of phenomenology initiated in the works of Husserl and continued in a wide range of works of others was immense, but mainly within the confines of philosophy and the humanities. The actual attempts to develop a scientific discipline of the study of consciousness and to carry out research on cognition and consciousness were always based on the methods of traditional science in which elimination of the subjective has been always a primary tenet. Thus, focus was mainly on neurological correlates of conscious phenomena. The present paper is an attempt to initiate an extension and revision of phenomenological methodology with the use of philosophical and scientific experience and knowledge accumulated in a century of inquiry and research in relevant disciplines. The question which disciplines are relevant is crucial and our answer is innovative. The range of disciplines involved here is from information science and studies of computation, up to cultural psychology and the studies of philosophical traditions of the East. Concepts related to information and computation studies provide a general conceptual framework free from the limitations of particular languages and of linguistic analysis. This conceptual framework is extending the original perspective of phenomenology to issues of modern technology and science. Cultural psychology gives us tools to root out what in phenomenology was considered universal for humanity, but was a result of European ethnocentrism. Most important here is the contrast between individualistic and collectivistic cultural determinants of consciousness. Finally, philosophical tradition of the East gives alternatives in seeking solutions for fundamental problems. This general outline of the research methodology is illustrated by an example of its use when phenomenology is studied within the conceptual framework of information. PMID- 26141000 TI - A new kind of relativity: Compensated delays as phenomenal blind spots. AB - The French phenomenologist Merleau-Ponty identified the human body as the blind spot of perception and cognition. Being situated in its environment both spatially and temporally, the body forms a primordial field of presence, which is transparent from the obserpant's(1) perspective and therefore creates a sytemic blindness. This paper is primarily concerned with what Merleau-Ponty calls the pulse of the duration of the body, which, in his view, "impregnates" our perception. This notion of duration will be described in terms of the temporal extensions of an embodied obserpant. For biological systems, these extensions may be measured in the obserpant's temporal endo-sphere, a time cone, which extends in two dimensions: succession and simultaneity (Deltatlength and Deltatdepth, respectively). Obserpants are described not as having, but being a model of the world (including themselves). The perception of Deltatlength and Deltatdepth results in a fractal temporal structure, which correlates with successive and instantaneous perception. This temporal structure becomes important during temporal recalibration, i.e. delay compensation. During such processes, the distribution of the temporal dimensions succession and simultaneity may vary from one obserpant's Now to another's. Furthermore, recalibration provides a window in which the obserpant's Now may be tipped towards either temporal dimension. We can measure the difference between obserpant A's temporal extension and that of obserpant B in Deltatlength and Deltatdepth. The complexity of an obserpant's temporal perspective - his temporal interface - can thus be compared and quantified by the size of his time cone. The units of this measurement are the number of compensated and uncompensated delays. During temporal recalibration, an obserpant can turn succession into simultaneity and vice-versa. Moreover, what is successive in obserpant A's Now may be simultaneous for obserpant B and vice versa. This discrepancy can be modelled as time cones which display a new kind of (Deltatlength-Deltatdepth-) relativity. This new kind of relativity arises from the oberpants' inability to spot the systemic blindness that manifests itself in anticipated, i.e. compensated, delays. PMID- 26141001 TI - Is it ethical to heal a young white elephant from his physiological autism? AB - Forty years ago a causal therapy of autism was offered which has never been tried out by the therapeutic profession. It predictably is so effective that even members of other mirror-competent bonding species can be healed from their "physiological autism." Niklas Luhmann belonged to the therapy's supporters and Leo Szilard had anticipated it in fiction 30 years earlier. The Ottersberg Lectures on Philosophy revived it through the enthusiasm and cooperation of the youthful audience. PMID- 26141002 TI - Cutaneous Ulcer at the Site of Radiation-Induced Dermatitis Caused by Infection With Vibrio alginolyticus. PMID- 26141003 TI - Does the treatment ladder for systemic therapy in moderate to severe psoriasis only go up? The percentage of patients with severe psoriasis on biologics increases over time. AB - BACKGROUND: With the advent of biologic drugs in the management of moderate to severe psoriasis, there may have been a shift in therapeutic approach from rotational strategies to a unidirectional progression from topical treatments to the highest rung of the therapeutic ladder. We studied the frequency of switching from classic to biologic therapy and vice versa in a cohort of patients with psoriasis over a period of up to 5 years. METHODS: Patients are included in the BIOBADADERM prospective registry when they are first prescribed any specific conventional or biologic systemic treatment. The data for each patient refer to the follow-up period from the time they entered the cohort until October 2013. To describe the pattern of switches from classic to biologic therapy and vice versa, we used the data in the registry on the first day of every 365-day period following the date each patient was included in the cohort. RESULTS: In total, 47.3% of the patients (926/1956) were prescribed a classic systemic drug and 52.7% (1030/1956) a biologic agent on entry into the study. Of the 741 patients who accumulated 5 years of follow-up, 21.9% (155) were receiving nonbiologic drugs and 78.1% (553) were on biologic therapy on the first day of their 5th year of follow-up. CONCLUSIONS: The proportion of patients receiving biologic therapy increased with longer follow-up. PMID- 26141004 TI - Rapid maxillary expansion (RME) for pediatric obstructive sleep apnea: a 12-year follow-up. AB - OBJECTIVE: The objective of this study was to prospectively evaluate the long term efficacy of rapid maxillary expansion (RME) in a group of children with obstructive sleep apnea (OSA). MATERIAL AND METHOD: Thirty-one children diagnosed with OSA were involved in the study. These children had isolated maxillary narrowing and absence of enlarged adenotonsils at baseline. Twenty-three individuals (73% of the initial group) were followed up annually over a mean of 12 years after the completion of orthodontic treatment at a mean age of 8.68 years. Eight children dropped out over time due to either moving out of the area (n = 6) or refusal to submit to regular follow-up (n = 2). Subjects underwent clinical reevaluation over time and repeat polysomnography (PSG) in the late teenage years or in their early 20s. During the follow-up period, eight children dropped out and 23 individuals (including 10 girls) underwent a final clinical investigation with PSG (mean age of 20.9 years). The final evaluation also included computerized tomographic (CT) imaging that was compared with pre- and post-initial treatment findings. RESULTS: Yearly clinical evaluations, including orthodontic and otolaryngological examinations and questionnaire scores, were consistently normal over time, and PSG findings remained normal at the 12-year follow-up period. The stability and maintenance of the expansion over time was demonstrated by the maxillary base width and the distance of the pterygoid processes measured using CT imaging. CONCLUSION: A subgroup of OSA children with isolated maxillary narrowing initially and followed up into adulthood present stable, long-term results post RME treatment for pediatric OSA. PMID- 26141005 TI - Response to the letter "Sleep characteristics of children with Williams syndrome in relation to saliva melatonin and cortisol". PMID- 26141006 TI - Pneumoparotid associated with a mandibular advancement device for obstructive sleep apnea. PMID- 26141007 TI - Sleep deprivation leads to mood deficits in healthy adolescents. AB - STUDY OBJECTIVES: The objectives of the study were to investigate the effects of 36 h of sleep deprivation on the discrete mood states of anger, depression, anxiety, confusion, fatigue, and vigour in healthy adolescents. METHOD: Twelve healthy adolescent good sleepers (six male), aged 14-18 years (M = 16.17, standard deviation (SD) = 0.83), spent three consecutive nights in the sleep laboratory of the Centre for Sleep Research: two baseline nights with 10-h sleep opportunities and one night of total sleep deprivation. Every 2 h during wakefulness, they completed the Profile of Mood States - Short Form. Mood across two baseline days was compared to mood at the same clock time (0900 h to 1900 h) following one night without sleep. RESULTS: The subscales of depression, anger, confusion, anxiety, vigour, and fatigue were compared across days. All mood states significantly worsened following one night without sleep. Females showed a greater vulnerability to mood deficits following sleep loss, with greater depressed mood and anxiety following sleep deprivation only witnessed among female participants. While both males and females reported more confusion following sleep deprivation, the magnitude of this effect was greater for females. CONCLUSIONS: This study provides empirical support for the notion that sleep loss can causally affect mood states in healthy adolescents, with females having heightened vulnerability. Understanding the detrimental effects of insufficient sleep during adolescence is important, as it is a stage where sleep loss and mood dysregulation are highly prevalent. These findings escalate the importance of promoting sleep for the well-being of adolescents at this critical life phase. PMID- 26141008 TI - Prevalence and determinants of subjective sleepiness in healthy elderly with unrecognized obstructive sleep apnea. AB - OBJECTIVE: Obstructive sleep apnea (OSA) is associated with behavioral consequences such as excessive daytime sleepiness (EDS). The aim of this study was to establish the presence of sleepiness in elderly with unrecognized OSA and the factors explaining its occurrence. METHODOLOGY: A total of 825 healthy elderly (aged >=65 years) undergoing clinical, respiratory polygraphy, and heart rate variability analysis were studied. According to the apnea-hypopnea index (AHI), the subjects were stratified in four categories: no-OSA (AHI <5), mild (5 > AHI <15), moderate (15 >= AHI <30), and severe OSA (AHI >=30). Participants with EDS were defined on the basis of the Epworth Sleepiness Scale (ESS) score >=10. RESULTS: Overall, the mean ESS score was 5.7 +/- 5.6, 14.9% showing EDS with an increasing trend according to OSA severity (p <0.001). Sleepy subjects were more frequently men, having a greater body mass index (BMI), alcohol intake, depression score, and indices of OSA severity (23% of severe OSA cases being sleepy). No differences were present between sleepy and non-sleepy subjects in regard to other clinical, metabolic, and autonomic nervous system measurements. Regression analyses adjusted for age, gender, BMI, hypertension, depression score, autonomic sleep fragmentation, and AHI and/or oxygen desaturation index revealed that gender (p <0.0001), depression score (p <0.0001), and BMI (p = 0.01) were the only significant factors affecting the presence of sleepiness in this population. CONCLUSIONS: In healthy elderly with OSA, the prevalence of EDS was low, and it affected only severe cases. Despite a weak association between the ESS score and the AHI index, male gender and depression score were the most significant predictors for the occurrence of sleepiness. PMID- 26141009 TI - Sleep characteristics of children with Williams syndrome in relation to saliva melatonin and cortisol. PMID- 26141010 TI - Editorial. PMID- 26141011 TI - Meningococcal serogroup B vaccine (4CMenB): Booster dose in previously vaccinated infants and primary vaccination in toddlers and two-year-old children. AB - OBJECTIVE: The multicomponent, recombinant serogroup B vaccine, 4CMenB, is approved in Europe, Canada and Australia from two months of age. We investigated persistence to booster doses at 12 months of age following infant vaccination, and immune response to catch-up vaccination of toddlers and children up to two years of age. METHODS: We assessed persistence of immune responses after one year in participants vaccinated as infants, and responses to two doses at 12-15 or 24 26 months of age in vaccine-naive children, as serum bactericidal activity with human complement (hSBA) against indicator strains for four vaccine antigens. Adverse events were recorded after each vaccination. RESULTS: High antibody titers were induced against all four 4CMenB components following booster vaccination in infant-primed toddlers and after two doses in previously unvaccinated toddlers or two-year-olds. Antibodies waned over 12 months, particularly those against NZ OMV. Systemic reactogenicity in toddlers was lower than in infants, and lower again in vaccine-naive two-year-olds. Local reactogenicity was common in all groups. CONCLUSIONS: Four infant or two toddler 4CMenB vaccinations elicit immune responses believed to be protective for the first two years of life, which can be boosted. Reactogenicity is lower in toddlers than in infants. PMID- 26141013 TI - Monoclonal antibody, mAb 4C13, an effective detoxicant antibody against ricin poisoning. AB - Ricin is a glycoprotein produced in castor seeds and consists of two polypeptide chains named Ricin Toxin A Chain (RTA) and Ricin Toxin B Chain (RTB), linked via a disulfide bridge. Due to its high toxicity, ricin is regarded as a high terrorist risk for the public. However, antibodies can play a pivotal role in neutralizing the toxin. In this research, the anti-toxicant effect of mAb 4C13, a monoclonal antibody (mAb) established using detoxicated ricin as the immunized antigen, was evaluated. Compared with mAb 4F2 and mAb 5G6, the effective mechanism of mAb 4C13 was analyzed by experiments relating to its cytotoxicity, epitope on ricin, binding kinetics with the toxin, its blockage on the protein synthesis inhibition induced by ricin and the intracelluar tracing of its complex with ricin. Our result indicated that mAb 4C13 could recognize and bind to RTA, RTB and exert its high affinity to the holotoxin. Both cytotoxicity and animal toxicity of ricin were well blocked by pre-incubating the toxin with mAb 4C13. By intravenous injection, mAb 4C13 could rescue the mouse intraperitoneally (ip) injected with a lethal dose of ricin (20MUg/kg) even at 6h after the intoxication and its efficacy was dependent on its dosage. This research indicated that mAb 4C13 could be an excellent candidate for therapeutic antibodies. Its potent antitoxic efficiency was related to its recognition on the specific epitope with very high affinity and its blockage of protein synthesis inhibition in cytoplasm followed by cellular internalization with ricin. PMID- 26141014 TI - Elastic liposome-mediated transdermal immunization enhanced the immunogenicity of P. falciparum surface antigen, MSP-119. AB - Transdermal immunization results in poor immunogenicity, which can be attributed to poor permeability of antigens through the skin. Therefore, elastic liposome, ultradeformable lipid vesicles, may overcome the challenges faced during transdermal immunization. This versatile carrier proves better vehicle for transcutaneous delivery of protein, peptide and nucleic acid antigens. The present results are suggestive of improved immunogenicity of carboxyl-terminal 19 kDa fragment of merozoite surface protein-1 (PfMSP-119) of Plasmodium falciparum when administered subcutaneously through elastic liposomes. The prepared elastic liposomes were characterized with respect to vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, stability and in vitro release. Humoral and cell-mediated immune (CMI) response elicited by topically applied PfMSP-119-loaded elastic liposomes, intramuscularly administered alum-adsorbed PfMSP-119 solution, and topically applied PfMSP-119 loaded conventional liposomes were compared and normalized with vehicle control. Results suggest greater transcutaneous immunization via elastic liposomes, and induced robust and perdurable IgG-specific antibody and cytophilic isotype responses. We report to have achieved sizeable CMI activating factor (IFNgamma), a crucial player in conferring resistance to asexual blood stage malaria, responses with elastic liposomes when compared with other formulations. The fluorescence microscopy and histopathology results are suggestive of prominent skin permeation and biodistribution, and demonstrate efficient delivery of malaria antigen via elastic liposomes to immunocompetent Langerhans cells (LC) and lymphatics. In conclusion, elastic liposomal formulation provided greater entrapment efficiency, enhanced penetration and heightened and long-lasting immune response. Moreover, effective immunoadjuvant property of this carrier justifies its potential for improved vaccine delivery, and opens new avenues to explore further on the development of malaria vaccine. PMID- 26141015 TI - Different inhaled allergen challenge models give reproducible results. PMID- 26141012 TI - Humoral immune responses to Streptococcus pneumoniae in the setting of HIV-1 infection. AB - Streptococcus pneumoniae (pneumococcus) remains one of the most commonly identified causes of bacterial infection in the general population, and the risk is 30-100 fold higher in HIV-infected individuals. Both innate and adaptive host immune responses to pneumococcal infection are important against pathogen invasion. Pneumococcal-specific IgA antibody (Ab) is key to control infection at the mucosal sites. Ab responses against pneumococcal infection by B cells can be generated through T cell-dependent or T cell-independent pathways. Depletion of CD4+ T cells is a hallmark of immunodeficiency in HIV infection and this defect also contributes to B cell dysfunction, which predisposes to infections such as the pneumococcus. Two pneumococcal vaccines have been demonstrated to have potential benefits for HIV-infected patients. One is a T cell dependent 13-valent pneumococcal conjugate vaccine (PCV13); the other is a T cell independent 23 valent pneumococcal polysaccharide vaccine (PPV23). However, many questions remain unknown regarding these two vaccines in the clinical setting in HIV disease. Here we review the latest research regarding B cell immune responses against pneumococcal antigens, whether derived from potentially invading pathogens or vaccinations, in the setting of HIV-1 infection. PMID- 26141016 TI - Gabapentin in chronic cough. AB - BACKGROUND: Chronic cough is regarded as a challenging clinical problem due to its frequency and often limited therapeutic options. Chronic cough that remains refractory to usual medical treatment causes significant quality of life impairment. METHODS: Recent developments in the treatment of cough include the use of speech pathology and pharmacotherapy with gabapentin. Relevant randomised control trials, reviews and case reports were identified through a PubMed and SCOPUS search of English-language literature referring to these concepts over the last eight years. RESULTS: The effectiveness of neuromodulating medications such as gabapentin and pregabalin in the treatment of cough has been supported primarily through case series, case reports, prospective reviews and a double blind randomised controlled trial. Gabapentin results in a reduction in cough frequency and cough severity. It improves cough related quality of life. The effect is greatest in patients with features of central reflex sensitisation such as laryngeal paraesthesia, hypertussia and allotussia. These symptoms can be measured using the Newcastle Laryngeal Hypersensitivity Questionnaire. Side effects of gabapentin include somnolence and dizziness. CONCLUSION: Recent additions in the treatment of chronic cough have been significant as they consider cough to have a unifying diagnosis of cough hypersensitivity with or without the presence of a neuropathic basis. Effective treatments for refractory chronic cough that target these areas include behavioural treatment such as speech pathology and pharmaceutical treatment with neuromodulating medications such as gabapentin. PMID- 26141017 TI - Neural dysfunction following respiratory viral infection as a cause of chronic cough hypersensitivity. AB - Respiratory viral infections are a common cause of acute coughing, an irritating symptom for the patient and an important mechanism of transmission for the virus. Although poorly described, the inflammatory consequences of infection likely induce coughing by chemical (inflammatory mediator) or mechanical (mucous) activation of the cough-evoking sensory nerves that innervate the airway wall. For some individuals, acute cough can evolve into a chronic condition, in which cough and aberrant airway sensations long outlast the initial viral infection. This suggests that some viruses have the capacity to induce persistent plasticity in the neural pathways mediating cough. In this brief review we present the clinical evidence of acute and chronic neural dysfunction following viral respiratory tract infections and explore possible mechanisms by which the nervous system may undergo activation, sensitization and plasticity. PMID- 26141018 TI - The role of immunohistochemistry in the evaluation of gynecologic pathology part 2: a comparative study between two academic institutes. AB - Use of specific immunohistochemistry (IHC) marker, singly or in panels, differs and is influenced by practice setting, individual experience beside other factors. This is a part 2 study where we surveyed the application of IHC in gynecologic (gyn) pathology. Our specific aim in this part was to identify what specific stains are preferentially used. A retrospective chart review on all cases accessioned to the gyn pathology specialty sign out service during a 1-year period was performed at two academic pathology departments. Outside referral and consult as well as gyn cytology cases were excluded from the study. The most commonly ordered markers in diagnostic gyn pathology in descending order of frequency were as follows: P16, ki-67, p53, estrogen receptor (ER), progesterone receptor (PR), and CK7. P16 was used mainly in establishing the diagnosis/grading of squamous intraepithelial lesions (SIL) and differentiating serous from endometrioid carcinomas (ECs). P53 was used particularly in the diagnosis of serous carcinomas and establishing the diagnosis of differentiated vulvar intraepithelial neoplasia. Positive p16 was documented in all high-grade SIL, endocervical carcinomas, and serous carcinomas. In contrast, p16 was negative in all benign, low-grade SIL, and ECs. ER and PR were used in panels with p16, p53, vimentin, and carcinoembryonic antigen to assign tumors to specific site, in differentiating EC from serous carcinomas and in establishing the diagnosis of endocervical adenocarcinomas. Immunohistochemistry was used in 4.7% and 8.7% of gyn surgical path cases at two institutions. P16, ki-67, and p53 were the most commonly used markers especially in grading SIL. This study documents the most commonly used IHC biomarkers at two tertiary care academic centers for defining benchmarks for IHC use. PMID- 26141019 TI - Associations between calcium and vitamin D supplement use as well as their serum concentrations and subclinical cardiovascular disease phenotypes. AB - BACKGROUND: Supplementation of calcium (Ca) and vitamin D for the prevention of osteoporosis is frequently found in Western countries. Recent re-analyses of clinical trials observed a higher risk of myocardial infarction and stroke in subjects taking Ca (+vitamin D) supplements, although the underlying mechanisms are not clear. OBJECTIVE: Thus, we analyzed the associations between Ca and vitamin D supplementation as well as serum concentrations of Ca and 25 hydroxyvitamin D (25(OH)D) and subclinical cardiovascular disease (CVD) phenotypes, namely intima-media thickness, ankle-brachial-index (ABI), intermittent claudication, and atrial fibrillation (AF). DESIGN: Data of 1601 participants aged 50-81 years of the population-based cross-sectional Cooperative Health Research in the Region of Augsburg (KORA) F4 study in Germany were analyzed. Logistic and linear regression models were used to estimate odds ratios (OR) (95% confidence intervals (CI)) and beta-estimates (p-values), respectively. RESULTS: Regular Ca supplementation showed a significant positive association with the presence of AF after multivariable adjustment (OR = 3.89; 95% CI 1.28 11.81). Higher serum 25(OH)D concentrations were independently associated with a lower prevalence of asymptomatic peripheral arterial disease as assessed by ABI measurements (beta = 0.007; p = 0.01). No other significant associations between supplementation or serum concentrations of Ca or vitamin D and CVD phenotypes were identified. CONCLUSIONS: Although based on few cases the finding of a significant higher prevalence of AF in Ca supplement users hints at one possible mechanism that may contribute to an increased risk of myocardial infarction and stroke. The observed association between serum 25(OH)D and ABI supports results from other studies. PMID- 26141020 TI - Isolated C5-C6 avulsion in obstetric brachial plexus palsy treated by ipsilateral C7 neurotization to the upper trunk: outcomes at a mean follow-up of 9 years. AB - Cervical root avulsions are the worst pattern of injury in obstetrical brachial plexus injury (OBPI). The prognosis is poor and the treatment is mainly surgical with extraplexual neurotizations or muscle transfers. We present the outcomes of a technique performed in our institution to treat C5-C6 avulsion in obstetrical brachial plexus injury. This technique consists of a total ipsilateral C7 neurotization to the upper trunk. Ten babies with isolated C5-C6 root avulsion were operated on; we were able to review nine of them at over 12 months follow up. The shoulder and the elbow function were assessed, as well as the Mallet Score. The mean follow-up was 9.2 years (SD 5.7). After a follow-up of 6 years, elbow flexion was restored with a range of motion ?130 degrees and a motor function ?M3 in all patients. The average Mallet score was 18.1 (SD 1.2). This approach appears to be a viable alternative to extraplexual neurotizations for the treatment of C5-C6 nerve root avulsion. PMID- 26141021 TI - Incidence of flexor tendon fraying found during A1 pulley release operation for trigger finger. PMID- 26141022 TI - A rare cutaneous transverse branch from the dorsal branch of the ulnar nerve. PMID- 26141023 TI - 'Matriderm' dermal substitute with split-thickness skin graft compared with full thickness skin graft for the coverage of skin defects after surgical treatment of congenital syndactyly: results in 40 commissures. PMID- 26141024 TI - Assessment of handgrip strength in preschool children aged 3 to 5 years. AB - We investigated whether there is an optimal grip span for determining the maximum handgrip strength in preschool children and if it is influenced by gender, age, or hand size. A total of 292 preschool children (3-5 years; 59.2% boys) carried out the handgrip strength test with different grip spans (4.0, 4.5, 5.0, 5.5, and 6.0 cm). The hand size was also measured. We also determined the reliability of the optimal grip span in another group of children (n = 56, 57% boys) who did the test twice, with a 3-hour difference between tests. The results showed that 4.0 cm is the optimal grip span to determine the maximum handgrip strength in preschool children. This result applied to both genders, all age groups, and hand sizes. Paired t-tests showed no significant differences between test and retest. These findings may guide clinicians and researchers in selecting the optimal grip span when measuring handgrip strength in preschool children.Level IV. PMID- 26141025 TI - Collateral ligament repair augmented by an A2 pulley flap for chronic ligament rupture of the finger metacarpophalangeal joint. PMID- 26141026 TI - Intraneural lipoma of the posterior interosseous nerve. PMID- 26141027 TI - Allergy for tree pollens and crustaceans: testing and treatment. PMID- 26141028 TI - The pleiotropic role of vitamin A in regulating mucosal immunity. AB - The effect of vitamin A on mucosal immunity has never been subjected to extensive studies until recently. We started to work in this area in the early 1970s when we observed that children with protein-calorie malnutrition (PCM) often had defective mucosal immunity, judging from the incidence of respiratory tract infections and diarrhea. We reported that these children had depressed secretory IgA (sIgA) levels in their nasal wash fluids. The IgA level in specimens collected from those superimposed with some degrees of vitamin A deficiency state appeared to be more severely affected. In order to better understand the underlying mechanism associated with this condition, we started to study more detail the deficiency state using experimental vitamin A-deficient rats. From a series of experiments using this animal model, we proposed that vitamin A was needed for transport and/or secretion of sIgA across the mucosa. This conclusion was based on the observation that the secretory component of sIgA synthesized by the epithelial cells of these vitamin A deficient animals was adversely affected as compared to the control animals. From that time onward, much progress has been made by several other groups showing that other mechanisms could also influence the integrity and immune function of the mucosa. For instance, recent studies demonstrated that retinoic acid which is a biologically active form of vitamin A has an essential role in mucosal homeostasis, controlling tolerance and immunity in these non-lymphoid tissues. Such a conclusion was made possible by the availability of sophisticated new molecular biology and genetic engineering techniques together with advances in the field of immunoregulation, e.g., the discovery of dendritic cells (DCs) and T helper cell subsets in 1980s, and the role of Toll-like receptors (TLRs) together with other innate immune regulators in controlling adaptive immune response in the early 1990s. These advances provided considerable new insights into the pleiotropic roles of vitamin A including educating mucosal DCs, differentiation of lymphocyte lineages and imprinting them with mucosal-homing properties as well as in regulating tolerance and immunity. The identification of a novel lymphocyte subpopulation, innate lymphoid cells (ILCs), at the beginning of this century has provided us with an additional insight into a new role of vitamin A in regulating homeostasis at the mucosal surface through influencing ILCs. Another new player that regulates intestinal homeostasis and mucosal immune response is microbiota whose composition is known to vary with vitamin A status. So it appears now that the role of vitamin A on mucosal immunity is far beyond regulating the adaptive Th1 Th2 cell response, but is highly pleiotropic and more complicating, e.g., polarizing the phenotype of mucosal DCs and macrophages, directing gut-homing migration of T and B cells, inducing differentiation of effector T cells and Treg subpopulation, balancing mucosal ILCs subpopulation and influencing the composition of microbiota. In this review, I will attempt to bring together these important advances to provide a comprehensive and contemporary perspective on the role of vitamin A in regulating mucosal immunity. PMID- 26141029 TI - Pro j 2 is mesquite profilin: molecular characteristics and specific IgE binding activity. AB - BACKGROUND: Pollens from mesquite (Prosopis juliflora) are potent allergen responsible in causing immediate hypersensitivity reactions in susceptible people in tropical countries. OBJECTIVE: This study aimed to clone, express and purify the mesquite pollen profilin (Pro j 2) as well as evaluating its nucleotide sequence homology in order to predict allergenic cross-reactivity with profilins of common allergenic plants. METHODS: Immunoblotting assay and specific ELISA were applied to determine the immunoreactivity of sera from 35 patients who were allergic to mesquite pollen. The mesquite profilin-coding sequence was cloned into PTZ57R/T vector and amplified. The cDNA of mesquite pollen profilin was then expressed in Escherichia coli using pET-21b (+) vector and puri?ed by one-step Ni2+ a?nity chromatography. IgE binding capacity of the recombinant mesquite profiling (rPro j 2) was analyzed by specific ELISA, immunoblotting, and inhibition assays. RESULTS: cDNA nucleotide sequencing revealed an open reading frame of 399bp encoding for 133 amino acids which belongs to the profilin family. Seventeen patients (17/35, 48.57%) had significant specific IgE level for rPro j 2. Immunodetection and inhibition assays indicated that puri?ed rPro j 2 might be similar as that in the crude extract. CONCLUSION: Pro j 2, as a new allergen from mesquite pollen, was produced in E. coli with an IgE-reactivity similar to that of its natural counterpart. The amino acid sequences homology analysis of mesquite profilin and several profilin molecules from other plants showed high degree of cross-reactivity among plant-derived profilins from unrelated families. PMID- 26141030 TI - Effects of Xingbi gel on leukotriene E4 and immunoglobulin E production and nasal eosinophilia in a guinea pig model for allergic rhinitis. AB - BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal airways.Many therapies do not have immediate effects,even which have side effects.However,the effects of Xingbi gel for the treatment of AR was investigated. OBJECTIVE: We investigated the effects of Xingbi gel on serum levels of leukotriene E4 (LTE4) and immunoglobulin E (IgE), as well as eosinophil counts in the nasal mucosa using a guinea pig model of allergic rhinitis (AR). METHODS: In addition to a healthy control group without AR, guinea pigs with AR were randomly divided into untreated AR control group, low-dose Xingbi gel (0.2483 g/mL) group, high-dose Xingbi gel (0.4966 g/mL) group, and budesonide group. RESULTS: Compared to the healthy controls, untreated AR guinea pigs had significantly higher ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts (p <0.01). Treatments with low-dose Xingbi gel, high-dose Xingbi gel, and budesonide significantly reduced the ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts as compared to untreated AR model guinea pigs (p <0.01). CONCLUSION: Xingbi gel alleviates AR in part through inhibiting LTE4 and IgE production and reducing eosinophilia in the nasal mucosa. PMID- 26141031 TI - Identification of a T cell surface molecule using a monoclonal antibody produced by TCR/CD3 complex immunization. AB - BACKGROUND: Several molecules are known to be involved in T-cell activation via the TCR/CD3 complex and while the mechanisms of late T cell signaling have been well characterized, the very early events are still not fully understood. OBJECTIVE: The aim of this study was to identify yet unknown molecules associated with the TCR/CD3 complex. RESULTS: To identify new molecules associated with the TCR/CD3 complex, a monoclonal antibody termed MT3 was produced by immunoprecipitated beads immunization. Colocalization of the MT3 mAb recognizing molecules with the TCR/CD3 complexes was verified by confocal microscopic analysis. The surface antigen recognized by MT3 antibody was expressed on a subpopulation of CD3+ T cells, and on both CD4+ and CD8+ lymphocytes. The antigen was also expressed on na?ve CD4+ T cells and on a subset of memory CD4+ T cells. In contrast, in the CD8 population, the majority of MT3+ cells were found in the na?ve population. The MT3 mAb recognizing molecules were also expressed on red blood cells but only in particular subjects. Similar to peripheral blood leukocytes, MT3 mAb recognizing molecules are exclusively expressed on T cell lines. CONCLUSIONS: Based on the cellular distribution patterns and confocal microscopic analysis, the MT3 mAb recognizing molecule that we investigated is proposed to be a TCR/CD3 associated molecule and might be involved in the antigen recognition of T cells. PMID- 26141033 TI - Dust mite infestation in cooking flour: experimental observations and practical recommendations. AB - BACKGROUND: The first documented case of oral mite anaphylaxis has recently been reported in Thailand, with mites possibly originating from cooking flour. OBJECTIVE: Our study was designed to assess the effects of cooking flours enhancement and storage conditions on mite proliferation and to provide practical recommendations to prevent mite anaphylaxis. METHODS: In a factorial experiment, six commercial brands of cooking flours were selected and either inoculated or set free of mites and stored in one of the four containers chosen for the study: original package, plastic bag, plastic box and glass bottle. The resulting experimental units where then stored at either room temperature or in a refrigerator (+4C). In order to determine levels of Der f 1 allergen, 0.1 gram of flour was sampled from each experimental unit and tested by ELISA. Sampling was carried out immediately after inoculation and subsequently at week 2, 4, 6, 8, 10, 12, 16 and 20. RESULTS: Levels of Der f 1 allergen in the inoculated samples increased significantly in all conditions 6 weeks after inoculation (p <0.001) and reached the highest levels at week 8. While experimental units left at room temperature showed higher levels of mite growth (p <0.001), no statistical differences were found among types of containers. The highest amount of Der f 1 was observed for Gogi, followed by Gold Label, tempura flour, corn flour, wheat flour and tapioca starch, respectively (p <0.01). CONCLUSIONS: In the context of our experiment, mites preferably grew in cooking flours containing high amounts of wheat at room temperature, particularly after 8 week of storage. According to our results, we thus advise to keep household cooking flour refrigerated and while the type of container does not matter, storage should not exceed 20 weeks. PMID- 26141032 TI - Association of soluble human leukocyte antigen-G with acute tubular necrosis in kidney transplant recipients. AB - BACKGROUND: Human leukocyte antigen (HLA)-G is a nonclassical HLA class I molecule that displays strong immune-inhibitory properties and has been associated with allograft acceptance. However, there are conflicting data on the correlation of soluble HLA-G (sHLA-G) and acute rejection and no data on the correlation with acute tubular necrosis in kidney transplantation. OBJECTIVE: To evaluate the association of sHLA-G level in early post-transplant period and allograft rejection/ and acute tubular necrosis (ATN) in kidney transplant recipients. METHODS: The sera procured before transplantation and serially on day 3 and day 7 after transplantation from 76 kidney transplant recipients were analyzed for the level of sHLA-G by enzyme-linked immunosorbent assay. RESULTS: The levels of sHLA-G from three serial sera did not differ between patients with acute rejection and patients without rejection. However, the sHLA-G levels on day 3 post-transplant and day 7 post-transplant in patients with ATN were significantly higher than that in patients without ATN (16.3 vs 9.85 U/ml, p = 0.018, for day 3 post-transplant and 12.47 vs 5.42 U/ml, p = 0.044, for day 7 post-transplant). In addition, the ROC analysis of sHLA-G for identifying patients with ATN showed that the area under curve was 0.67 (95% confidence interval 0.54-0.80). CONCLUSIONS: There was no significant difference for sHLA-G levels between patients with acute rejection and without rejection. Interestingly, high levels of sHLA-G in day 3 and day 7 after transplantation were associated with acute tubular necrosis. Our findings raise the question whether the increased levels of sHLA-G in patients with acute tubular necrosis after transplantation might be a result of ischemia and reperfusion injury. PMID- 26141034 TI - Assessing the efficacy of a novel temperature and humidity control machine to minimize house dust mite allergen exposure and clinical symptoms in allergic rhinitis children sensitized to dust mites: a pilot study. AB - BACKGROUND: House dust mite avoidance is advised in dust mite sensitized patients to decrease the risk to develop allergic symptoms. Maintaining a relative humidity (RH) of less than 50% in households is recommended to prevent dust mite proliferation. OBJECTIVE: To investigate the efficacy of a novel temperature and humidity machine to control the level of dust mite allergens and total nasal symptom score (TNSS) in dust mite sensitized allergic rhinitis children. METHOD: Children (8-15 years) with dust mite sensitized persistent allergic rhinitis (AR) were enrolled. The temperature and humidity control machine was installed in the bedroom where the enrolled children stayed for 6 months. TNSS was assessed before and every month after machine set up and the level of dust mite allergen (Der p 1 and Der f 1) from the mattress were measured before and every 2 months after machine set up using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 7 children were enrolled. Noticeable reduction of Der f 1 was observed as early as 2 months after installing the machine, but proper significant differences appeared 4 months after and remained low until the end of the experiment (p <0.05). Although no correlation was observed between TNSS and the level of dust mite allergens, there was a significant reduction in TNSS at 2 and 4 months (p <0.05) and 70% of the patients were able to stop using their intranasal corticosteroids by the end of the experiment. CONCLUSIONS: The level of house dust mite in mattresses was significantly reduced after using the temperature and humidity control machine. This machine may be used as an effective tool to control clinical symptoms of dust mite sensitized AR children. PMID- 26141035 TI - Stability and potency of raw and boiled shrimp extracts for skin prick test. AB - BACKGROUND: The difference of stability between raw and boiled shrimp extracts used in prick tests has never been investigated despite its potential consequences in tests development. The aim of this study was to compare the raw and boiled shrimp extracts of two species; Macrobrachium rosenbergii (freshwater shrimp) and Penaeus monodon (seawater shrimp) held at 4 ?C for different periods of time for their stability and potency in vivo by using the skin prick test (SPT) method. METHODS: Raw and boiled M. rosenbergii and P. monodon extracts were prepared and stored at 4 ?C for 1, 7, 14 and 30 days. Thirty patients were pricked with raw and boiled shrimp extracts at all storage times, as well as prick to prick skin test (PTP) to fresh raw and boiled shrimps of both species. The mean wheal diameter (MWD) resulting from prick tests for all shrimp extracts was measured and compared. RESULTS: The shrimp extracts of all storage times yielded positive skin test results in the range of 90% - 100%. Raw P. monodon extracts induced larger wheals than boiled extracts at all storage times. There was no significant difference of MWD between raw and boiled M. rosenbergii extracts on day 1, 7, and 14. Significant correlations between MWD of PTP to fresh shrimps and SPT to all shrimp extracts were observed. All shrimp extracts were sterile at all storage times. CONCLUSIONS: Raw and boiled M. rosenbergii and P. monodon extracts were stable and sterile at 4 ?C for at most 30 days. SPT with these extracts induced more than 10 mm in shrimp allergy patients and the results were comparable with PTP to fresh shrimps. PMID- 26141036 TI - Analysis of various risk factors predisposing subjects to allergic rhinitis. AB - BACKGROUND: In Korea, the prevalence of allergic rhinitis (AR) is increasing, as in other industrialized countries. However, no large population-based study defining risk factors for AR has yet been conducted. OBJECTIVE: The purpose of this study was to evaluate the prevalence and risk factors of AR in large population-based study. METHODS: A cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey. We evaluated data from 31,217 subjects who were interviewed between 2008 and 2011. RESULTS: The prevalence of AR decreased with age (adjusted odds ratio [AOR] = 0.985; 95% CI = 0.984-0.987). Higher-level stress (AOR for severe stress = 1.470; 95% CI = 1.209-1.788); asthma (AOR = 1.868; 95% CI = 1.582-2.205); atopic dermatitis (AOR = 1.552; 95% CI = 1.309-1.841); pulmonary tuberculosis (AOR = 1.320; 95% CI = 1.119-1.555); depression (AOR = 1.250; 95% CI = 1.117-1.400); and thyroid disease (AOR = 1.328; 95% CI = 1.104-1.597) increased the risk of AR. Participants whose parents had a history of AR also had higher AORs (father, AOR = 1.566; 95% CI = 1.130-2.172; mother, AOR = 1.546; 95% CI = 1.190-2.008). Marriage (AOR = 0.846; 95% CI = 0.741-0.966) decreased the risk of AR. Farmers, fishers, laborers, and soldiers were at lower risk of AR. Although high BMI, a high educational level, living in a large household, specific types of daily living, and a history of diabetes mellitus have been reported as risk factors for AR; none of these factors attained statistical significance in the present study. CONCLUSION: Our study revealed that age, stress level, marriage, occupation, asthma, atopic dermatitis, pulmonary tuberculosis, depression, thyroid disease, and parental AR history, all affected the prevalence of AR. We believe that defining the influence of various factors on AR will help to prevent development of the condition in the future. PMID- 26141037 TI - Risk of asthma in relation to occupation: A hospital-based case-control study. AB - BACKGROUND: Asthma is a common occupational lung disease and is preventable by removing identifiable allergens. OBJECTIVES: (1) To assess the relationship between occupation and asthma (2) To determine the agents associated with asthma. METHODS: In this hospital-based, case-control study 153 cases from the Asthma Clinic and 306 non-asthmatic controls from Srinagarind Hospital, Thailand were interviewed. Crude odds ratios (COR), 95% confidence intervals (95% CI) and adjusted ORs (AOR) for multiple logistic regression were calculated. RESULTS: Of the 153 cases, 70.6% were females with median age of 53 (IQR-14). Of the 306 controls, 62.4% were females with median age of 56 (IQR-16). The highest risk of asthma was family history of asthma and history of atopy [AOR 11.68 (95% CI 4.52, 30.24) and AOR 8.03 (95% CI 5.07, 13.60)], respectively. If only occupations were considered, healthcare workers had the highest risk [AOR 4.08 (95% CI 1.35, 12.30)], followed by textile workers [AOR 3.34 (95% CI 1.07, 10.47)] and school workers AOR 2.40 (95% CI 1.31, 4.41). When subgroups of non-atopy were considered, school workers had a significant association with asthma [COR 3.18 (95% CI 1.48, 6.83)]. When no family history of asthma was considered, school and textile workers had the most significant association with asthma [COR 3.10 (95% CI 1.87, 5.13) and COR 3.06 (95% CI 1.15, 8.13), respectively]. Inorganic dust was the agent most significantly associated with asthma COR 1.89 (95% CI 1.25, 2.82). CONCLUSION: School, textile and healthcare workers have the greatest risk of asthma. Family history of asthma and being atopic would also promote asthma in relation to occupation. PMID- 26141038 TI - The natural course of childhood atopic dermatitis: a retrospective cohort study. AB - BACKGROUND: Atopic dermatitis (AD) is generally considered to be the initial step of the so-called atopic march, which following steps are allergic rhinitis (AR) and asthma. There are few data about the progression of AD, including factors associated with the remission of AD in Asians and further research is needed. OBJECTIVE: To study the progression and factors associated with the remission of childhood AD diagnosed by pediatric dermatologists. METHODS: This study included 303 AD patients who visited the pediatric dermatology unit at King Chulalongkorn Memorial Hospital, Thailand, between 2002 and 2010. An interview, performed by a physician via telephone using a preformed questionnaire, was completed for 205 children. RESULTS: A total of 205 children were observed, with a median observation time of 5.2 (3.5-8.0) years, and an initial AD severity score of mild (61.0%), moderate (29.3%) and severe (9.7%). The prevalence of AD during the first two years of life was 64.4%. AD completely disappeared in 102 cases (49.8%) by the median age of 3.5 (1.5-7.8) years. Early onset and severity of AD were major determinant of prognosis. The prevalence of AR and asthma was 36.6%, and 9.3%, respectively. The risk factors associated with respiratory allergy were the onset of AD after aged two years, a family history of atopy, increased serum IgE level, and sensitization to inhalant allergens. CONCLUSIONS: Half of AD had completely disappeared at preschool age. Good prognosis was mostly determined by early onset AD and mild severity. Late onset, family history of atopy and increased serum IgE level are associated with respiratory allergy. PMID- 26141039 TI - Clinical performance of a low cost near infrared sensor for continuous glucose monitoring applied with subcutaneous microdialysis. AB - In this work we present a low cost, minimally invasive, and chip-based near infrared (NIR) sensor, combined with subcutaneous microdialysis, for continuous glucose monitoring (CGM). The sensor principle is based on difference absorption spectroscopy in the 1st overtone band known to be dominated by glucose-specific absorption features. The device comprises a multi-emitter LED and InGaAs photodiodes, which are located on a single electronic board (non-disposable part), connected to a personal computer via Bluetooth. The disposable part consists of a chip containing the fluidic connections for microdialysis, two fluidic channels acting as optical transmission cells and total internally reflecting mirrors for in- and out-coupling of the light to the chip and to the detectors. The use of the sensor in conjunction with a subcutaneous microdialysis catheter to separate the glucose from the cells and proteins has been demonstrated to be extremely useful and advantageous for obtaining continuous glucose monitoring data and detecting glycemic levels in real time for a long period. Several in vitro and in vivo experiments were conducted to test the reliability of the device. In vitro measurements showed a linear relationship between glucose concentration and the integrated difference signal with a coefficient of determination of 99 % at the physiological concentration range. Clinical trial on 6 subjects with Type 1 diabetes showed that the NIR-CGM sensor data reflects the blood reference values adequately, if a proper calibration and signal drift compensation is applied. The MARD (mean absolute relative difference) value taken on retrospective data over all subjects is 8.5 % (range 6 11.5 %). PMID- 26141040 TI - Retraction Note: A translocator protein ligand PK11195 shows antigrowth activity in human choriocarcinoma cells. PMID- 26141041 TI - Upregulated expression of polycomb protein Ring1 contributes to poor prognosis and accelerated proliferation in human hepatocellular carcinoma. AB - Ring finger protein 1 (Ring1) have recently been reported to be closely related to aggressive tumor features in multiple cancer types, including prostate cancer, non-small-cell lung cancer, and bladder cancer. However, the role of Ring1 in human hepatocarcinogenesis remains unclear. In this study, we aimed at investigating the latent role of Ring1 in hepatocellular carcinoma (HCC) development. The expression of Ring1 was evaluated using Western blot analysis in 8 paired fresh HCC tissues and immunohistochemistry on 98 paraffin-embedded sections from 2005 to 2008. Moreover, RNA interference, CCK-8, colony formation, and flow-cytometry analyses were performed to investigate the role of Ring1 in the regulation of HCC cell proliferation. Compared with adjacent normal tissues, the level of Ring1 was significantly increased in HCC specimens. High expression of Ring1 was associated with histological grade (P = 0.011) and tumor size (P = 0.004), and Ring1 expression was positively related with the proliferation marker Ki-67 (P < 0.001). Moreover, knocking down Ring1 induced growth impairment and G1/S cell cycle arrest in HCC cells. Kaplan-Meier survival curves showed that high expression of Ring1 indicated poor prognosis of HCC (P = 0.03). On the basis of these results, we proposed that the expression of Ring1 protein may be a novel indicator of HCC prognosis. PMID- 26141042 TI - Frequency and subtype of BK virus infection in Iranian patients infected with HIV. AB - Human polyomavirus BK virus (BKV) is a double-stranded DNA virus that infects approximately 90 % of the general population as a subclinical or mild infection. In immunosuppressed patients, such as HIV cases, BKV may be reactivated resulting hemorrhagic cystitis and tubulointerstitial nephritis. However, there are limited studies on prevalence and molecular epidemiology of BKV in Iran. We therefore aimed to evaluate the prevalence and subtypes of BKV in Iranian HIV patients. A total of 99 patients with HIV infection were enrolled in the study. Presence of BKV DNA in plasma was evaluated by nested PCR. PCR products were sequenced directly, and phylogenetic analysis was performed. BKV DNA was detected in 8.08 % of HIV patients. BKV viremia presented in 4 out of 25 patients (16 %) not receiving antiretroviral therapy in comparison with 4 out 74 of HAART-treated patients (5.4 %) (P = 0.023). In patients with CD4 counts >=200 cells/mm(3), viremia was found more commonly (7/80 = 8.8 %) than in those with lower counts (1/19 = 5.2 %) (not significant). All sequenced BKV isolates belonged to subtype Ib-2. Our findings indicated that the prevalence of BKV viremia is relatively prevalent in patients with HIV infection and significantly higher in naive than HAART-treated cases. Therefore, HAART can eliminate BKV infection from plasma and reduce viremia although the actual implication of BKV viremia in HIV patients is not clear. PMID- 26141043 TI - miRNA-based drought regulation in wheat. AB - MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that regulate gene expression by guiding target mRNA cleavage or translational inhibition. Drought is a common environmental stress influencing crop growth and development. To date, it has been reported that a number of plant miRNA are involved in drought stress response. In this study, we comparatively investigated drought stress-responsive miRNAs in the root and leaf of bread wheat (Triticum aestivum cv. Sivas 111/33) by miRNA microarray screening. miRNA microarray analysis showed that 285 miRNAs (207 upregulated and 78 downregulated) and 244 miRNAs (115 upregulated and 129 downregulated) were differentially expressed in leaf and root tissues, respectively. Among the differentially expressed miRNAs, 23 miRNAs were only expressed in the leaf and 26 miRNAs were only expressed in the root of wheat growth under drought stress. Upon drought treatment, expression of miR159, miR160, miR166, miR169, miR172, miR395, miR396, miR408, miR472, miR477, miR482, miR1858, miR2118, and miR5049 were found to be significantly differentiated in bread wheat. The regulatory network analysis showed that miR395 has connections with a number of target transcripts, and miR159 and miR319 share a number of target genes. Drought-tolerant and drought-sensitive wheat cultivars showed altered expression pattern upon drought stress in terms of investigated miRNA and their target transcript expression level. PMID- 26141044 TI - Removable plate treatment of anterior forced crossbite: Effectiveness, efficiency, and potential outcome predictors. AB - OBJECTIVES: In addition to studying the effectiveness and efficiency of removable acrylic plates in correcting anterior forced crossbite, the influence of outcome predictors were evaluated. METHODS: In all, 65 patients met the inclusion criteria of anterior forced crossbite, mixed dentition, removable plate treatment, and complete case documentation. Effectiveness was assessed based on pre- and posttreatment study casts (which were analyzed for successful treatment outcomes defined as >= 1 mm of overjet and overbite) and efficiency was assessed based on treatment duration and number of appointments. Potential outcome predictors were also evaluated, including age, gender, dental maturity, Angle Class, number of teeth in crossbite, severity of crossbite, overbite, ANB angle, Wits appraisal, mandibular plane angle, and patient compliance. RESULTS: Successful crossbite correction was achieved in 48 of the 65 patients (74%) within a median of 2.8 months and 2.0 appointments. Plate treatment was discontinued following another median of 11.6 months and 6.5 appointments. Promising outcome predictors are the number of teeth in crossbite (1-2 versus 3-4 teeth = success in 81 versus 42% of cases), dental maturity (early versus late mixed dentition = success in 84 versus 52% of cases), and Angle Class (I versus III = success in 83 versus 61% of cases). CONCLUSION: Removable acrylic plates were found to be moderately effective and efficient in correcting anterior forced crossbite. Children presenting with Angle Class I and crossbites involving not more than two teeth when treatment is started during the period of early mixed dentition had the best prognosis for treatment success. PMID- 26141045 TI - Agenesis of second premolars and delayed dental maturation. AB - AIM: The purpose of this work was to examine the relationship between second premolar agenesis and how rapidly permanent dentition develops. METHODS: Panoramic radiographs of 678 girls and boys aged 6-14 years were evaluated. Subjects with syndromes or history of tooth extraction were excluded. The permanent dentition's stages of mineralization (scale 1-10) and eruption (1-7), and the resorption (1-5) of deciduous teeth were assessed. RESULTS: Adjusted for age and sex, subjects with one or more missing second premolars revealed earlier developmental stages (mineralization: average -0.37 stages per tooth, 95% CI 0.23 to -0.50; eruption: -0.42, 95% CI -0.60 to -0.24; resorption: -0.36, 95% CI 0.49 to -0.24; all p < 0. 001). Canines, premolars, and second molars were particularly affected, regardless of their location in the same or opposing jaw, and independent of the number of missing teeth. Overall dental development was delayed by 8.6 months (95% CI 5.4-11.8) in subjects with missing second premolars. CONCLUSION: These results have implications for several areas of medicine. Joint biological etiology for the agenesis and late maturation of permanent teeth should be considered in developmental research. Orthodontists should be aware of the delay associated with missing second premolars when timing interventions. Forensic age assessment based on tooth development should adjust for missing teeth to avoid underestimating the subject's age. PMID- 26141046 TI - Prospective study of the reproducibility of X-rays and CT scans for assessing trochanteric fracture comminution in the elderly: a series of 110 cases. AB - BACKGROUND: Trochanteric fractures are common but difficult to analyse in the elderly on plain X-rays. Fixation failures are related to the severity of the comminution, but comminution and the degree of instability are not easy to determine on standard X-rays. Use of computed tomography (CT) improves assessment of complex fractures, but this finding has not been confirmed versus intraoperative data. The primary objective of this prospective study was to determine the error rate when evaluating comminution on X-rays and CT scans. The secondary objectives were to determine whether CT data on comminution and stability were consistent with intraoperative findings and to define the fracture characteristics. HYPOTHESIS: Standard X-ray assessment underestimates the complexity of trochanteric fractures and is not very reproducible. METHODS: Between January and December 2013, all proximal femur fractures in the trochanter area of patients aged 75 years or older (mean age 85) were analysed prospectively with standard X-rays and computed tomography (CT). One hundred and ten patients (88 women and 22 men) with trochanteric fractures were included in the study. Fracture stability was evaluated using the Muller AO classification; the other fracture characteristics were evaluated independently. A senior surgeon evaluated the anonymised X-rays. A radiologist specialised in musculoskeletal imaging interpreted the CT scan images. All patients underwent total hip arthroplasty (110 patients) and 104 fixations of the greater trochanter. The X-ray and CT findings were compared to the intraoperative findings (gold standard) to evaluate their reproducibility. RESULTS: The reproducibility of the X-ray evaluation was poor for comminution, with a kappa of 0.4, sensitivity of 44 % and a negative predictive value of 29 % but a positive predictive value and specificity of 100 %. The CT evaluation had a kappa of 0.94, sensitivity of 95 % and negative predictive value of 79 %. According to the AO classification, unstable fractures were found in 65 patients based on X-rays, 80 patients based on CT scan and 83 patients based on intraoperative findings. Comminution was mainly identified during surgery; it was medial in 34 % of cases, posterior in 22 % and posteromedial in 21.8 %. DISCUSSION AND CONCLUSION: In the current study, 75.4 % of fractures were complex and unstable, with medial and/or posterior comminution present in three-quarters of these fractures. X-ray assessment underestimates posterior comminution and the complexity of the fracture line and was not very reproducible. The current results of this study suggest that comminution contributes to instability and that this finding is not taken into account in the AO classification, which is not well suited for this type of fracture and raises the question of how to best evaluate and treat these fractures. LEVEL OF EVIDENCE: Prospective diagnostic study, Level III. PMID- 26141047 TI - Support Needs of Families Living with Children with Autism Spectrum Disorder. AB - This study examined the perceived availability and helpfulness of supports used by caregivers of children with Autism Spectrum Disorder in New Zealand, particularly for caregivers who are Maori, and who live rurally. Caregivers (N = 92) completed the Family Support Scale with comparisons analysed using t tests. Free text comments were invited and analysed using a general inductive approach. More support was perceived as available by Non-Maori than Maori p = 0.03, 95 % CI (0.21, 3.88). Spouses were rated as the most helpful support. Professional helpers were rated as 'somewhat helpful'. Helpful support emphasised caring, knowledge and accessibility. Ethnic differences in perceptions of support endorse calls for culturally tailored supports. Informal supports are highly valued however professional supports require development to better meet caregiver needs. PMID- 26141048 TI - Which AO/OTA 31-A2 pertrochanteric fractures can be treated with a dynamic hip screw without developing a lateral wall fracture? A CT-based study. AB - PURPOSE: To determine whether radiographic measurements derived from standard computed tomography (CT) evaluation can be used to predict likelihood of a peri operative lateral femoral wall fracture in AO/OTA 31-A2 pertrochanteric fractures treated with a dynamic hip screw (DHS). METHODS: Fifty-one patients with AO/OTA 31-A2 classified pertrochanteric fractures were evaluated using a pre-operative CT scan of the pelvis with both hips. Dimensions of the lateral wall were calculated for each patient using four parameters: (1) height of the lateral wall above the vastus ridge; (2) circumference of the lateral wall 2 cm below the vastus ridge at an angle of 135 degrees ; this circumference was further divided into an anterior, lateral and posterior component; (3) cortical thickness at the centre of the lateral component of the lateral wall; and (4) cortical index. All patients were treated with a 135 degrees DHS. Postoperative radiographs were assessed for lateral femoral wall fracture. RESULTS: Patients with a lateral wall fracture (17/51) had a smaller circumference (4.47 cm vs 5.44 cm p value <0.001) as well as a lower height of the lateral femoral wall (1.37 cm vs 2.21 p value < 0.001). Analysis of the three components of the circumference revealed a significant difference for the anterior component only and not for the lateral and posterior components. There was no statistical difference in the cortical thickness or cortical index in the two groups. The cutoff values for height of the lateral wall and anterior component were calculated using ROC curves and found to be 1.68 cm (AUC 0.918) and 2.10 cm (AUC 0.851) respectively. CONCLUSION: AO/OTA 31-A2 pertrochanteric fractures with a lateral wall height of > 1.68 cm and an anterior component of > 2.10 cm in circumference are not likely to sustain a lateral wall fracture when treated with a DHS. PMID- 26141049 TI - Role of NR1I2 (pregnane X receptor) polymorphisms in head and neck squamous cell carcinoma. AB - The pregnane X receptor (PXR) is a transcription factor regulating genes involved not only in pharmacokinetics but also in chemotherapy resistance and cancer progression. The significance of PXR for survival of head and neck squamous cell carcinoma (HNSCC) patients is unknown so far. Single nucleotide polymorphisms (SNPs) in the PXR-encoding NR1I2 gene influence receptor functionality and inducibility by ligands and thus modulate expression and activity of its target genes. In this study, seven SNPs in the NR1I2 gene were investigated for an association with PXR protein expression and survival of HNSCC patients. Genotyping was conducted using hybridisation probe format methodology. PXR protein expression was quantified by immunohistochemistry of tissue microarray samples of HNSCC biopsies. Genotypes were correlated to PXR protein expression by a linear model regressing on the continuous gene expression value and a Cox model regressing on overall survival times. Haplotype analysis was performed by reconstruction of haplotypes from genotype information according to the expectation-maximisation algorithm. Of all tested SNPs, rs1054190 and rs1054191 allele variants tended to correlate with a reduced protein expression score of PXR (p = 0.088). Four haplotypes, each consisting of two SNPs, rs3814055/rs1054190 and rs3814055/rs1054191 as well as rs1523127/rs1054190 and rs1523127/rs1054191, showed a significant reduction of the PXR expression score (p = 0.049 and p = 0.032). However, neither allele variants nor haplotypes influenced overall survival of the respective patients. Certain NR1I2 SNPs showed an impact on PXR protein expression in HNSCC but did not influence overall survival times, questioning their value as prognostic biomarkers. PMID- 26141051 TI - AFM visualization of cortical filaments/network under cell-bound membrane vesicles. AB - While circulating/plasma membrane vesicles have been extensively characterized, due to the lack of effective methods cell-bound membrane vesicles are poorly understood including their shape and correlation with the intracellular cytoskeleton. In this study, we focused on cell-bound membrane vesicles and individual vesicle-derived pits on endothelial cells by using confocal microscopy and atomic force microscopy (AFM). For the first time, we found that cell-bound membrane vesicles are hemisphere-shaped and that the actin cortical filaments/network lies at the cytosolic opening of a vesicle instead of being closely attached to the inner side of the vesicle membrane. This structure of cell-bound membrane vesicles may be beneficial to their movement in, or release from, the plasma membrane of cells due to less membrane-cytoskeleton coupling to be broken therefore probably minimizing energy consumption and time usage. Further study indicates that TNF-alpha activation induced a significant increase in average number/size of cell-bound vesicles and the local disruption of the actin network at the cytosolic opening of cell-bound vesicles. PMID- 26141050 TI - Hepatitis E Virus in Domestic Pigs, Wild Boars, Pig Farm Workers, and Hunters in Estonia. AB - While hepatitis E is a growing health concern in Europe, epidemiological data on hepatitis E virus (HEV) in Estonia are scarce. Along with imported HEV infections, autochthonous cases are reported from European countries. Both domestic and wild animals can be a source of human cases of this zoonosis. Here, we investigated the presence of anti-HEV antibodies and HEV RNA in domestic pigs and wild boars, as well as in pig farm workers and hunters in Estonia. Anti-HEV antibodies were detected in 234/380 (61.6%) of sera from domestic pigs and in all investigated herds, and in 81/471 (17.2%) of meat juice samples from wild boars. HEV RNA was detected by real-time PCR in 103/449 (22.9%) of fecal samples from younger domestic pigs and 13/81 (16.0%) of anti-HEV-positive wild boar samples. Analysis of sera from 67 pig farm workers and 144 hunters revealed the presence of HEV-specific IgG in 13.4 and 4.2% of the samples, respectively. No HEV RNA was detected in the human serum samples. Phylogenetic analyses of HEV sequences from domestic pigs and wild boars, based on a 245 bp fragment from the open reading frame 2 showed that all of them belonged to genotype 3. The present study demonstrates the presence of HEV in Estonian domestic pig and wild boar populations, as well as in humans who have direct regular contact with these animals. Our results suggest that HEV infections are present in Estonia and require attention. PMID- 26141059 TI - Surface display of an anti-DEC-205 single chain Fv fragment in Lactobacillus plantarum increases internalization and plasmid transfer to dendritic cells in vitro and in vivo. AB - BACKGROUND: Lactic acid bacteria (LAB) are promising vehicles for delivery of a variety of medicinal compounds, including antigens and cytokines. It has also been established that LAB are able to deliver cDNA to host cells. To increase the efficiency of LAB-driven DNA delivery we have constructed Lactobacillus plantarum strains targeting DEC-205, which is a receptor located at the surface of dendritic cells (DCs). The purpose was to increase uptake of bacterial cells, which could lead to improved cDNA delivery to immune cells. RESULTS: Anti-DEC-205 antibody (aDec) was displayed at the surface of L. plantarum using three different anchoring strategies: (1) covalent anchoring of aDec to the cell membrane (Lipobox domain, Lip); (2) covalent anchoring to the cell wall (LPXTG domain, CWA); (3) non-covalent anchoring to the cell wall (LysM domain, LysM). aDec was successfully expressed in all three strains, but surface location of the antibody could only be demonstrated for the two strains with cell wall anchors (CWA and LysM). Co-incubation of the engineered strains and DCs showed increased uptake when anchoring aDec using the CWA or LysM anchors. In a competition assay, free anti-DEC abolished the increased uptake, showing that the internalization is due to specific interactions between the DEC-205 receptor and aDec. To test plasmid transfer, a plasmid for expression of GFP under control of an eukaryotic promoter was transformed into the aDec expressing strains and GFP expression in DCs was indeed increased when using the strains producing cell-wall anchored aDec. Plasmid transfer to DCs in the gastro intestinal tract was also detected using a mouse model. Surprisingly, in mice the highest expression of GFP was observed for the strain in which aDec was coupled to the cell membrane. CONCLUSION: The results show that surface expression of aDec leads to increased internalization of L. plantarum and plasmid transfer in DCs and that efficiency depends on the type of anchor used. Interestingly, in vitro data indicates that cell wall anchoring is more effective, whereas in vivo data seem to indicate that anchoring to the cell membrane is preferable. It is likely that the more embedded localization of aDec in the latter case is favorable when cells are exposed to the harsh conditions of the gastro-intestinal tract. PMID- 26141060 TI - PD-L1 induces epithelial-to-mesenchymal transition via activating SREBP-1c in renal cell carcinoma. AB - The incidence of kidney cancer has been increasing globally during the past two decades. Renal cell carcinoma (RCC) is the most aggressive subtype of kidney cancer, which usually deteriorates with epithelial-mesenchymal transition (EMT) that facilitates the migration and invasion of cancer cells. Till now, the underlying mechanism remains unclear. In this study, we demonstrated that programmed death ligand 1 (PD-L1/B7-H1/CD274) could induce EMT and enhance RCC cell cancer stemness through up-regulation of SREBP-1c. Furthermore, we found that PD-L1 is up-regulated in human RCC metastases. These results, taken together, provide evidence for a novel mechanism of PD-L1 in RCC progression, suggesting that there is a close relationship between EMT and immune escape signaling pathways in RCC. PMID- 26141062 TI - Tobacco consumption in the Kingdom of Saudi Arabia, 2013: findings from a national survey. AB - BACKGROUND: Tobacco consumption is a major risk factor for morbidity and mortality. The Saudi Ministry of Health started a national tobacco control program in 2002 with increased and intensified efforts after joining the World Health Organization Framework Convention for Tobacco Control in 2005. METHODS: In order to assess the status of tobacco consumption in the Kingdom of Saudi Arabia (KSA), we conducted a survey on 10735 individuals aged 15 years or older (5253 men and 5482 women) which was performed between April and June 2013. The Saudi Health Interview Survey had a multistage sampling and was nationally representative. Data were collected through face-to-face interviews. The survey included questions on socio-demographic characteristics, tobacco consumption, diet, physical activity, health care utilization, different health-related behaviors, and self-reported chronic conditions. RESULTS: Overall prevalence of current smoking was 12.2 % and males were more likely to smoke than females (21.5 % vs. 1.1 %). Mean age of smoking initiation was 19.1 years (+/-6.5 years) with 8.9 % of ever smokers starting before the age of 15 years. Daily shisha smoking was reported by 4.3 % of the population (7.3 % of men and 1.3 % of women). Around 1.4 % of population (2.6 % of men and 0.1 % of women) were daily smokers of cigarette/cigar and shisha. Receiving advice for quitting smoking by health care professionals during the last 12 months was reported by 53.2 % (95 % confidence interval [CI]: 49.8-56.5) of ever smokers. Among ever smokers, 51.3 % of individuals reportedly attempted to quit smoking during the last 12 months. Of those, 25.3 % were successful by the time of the survey. Around 23.3 % of the entire population, 32.3 % of men and 13.5 % of women, were exposed to secondhand smoke for at least one day during the past 7 days at home, work, or school. CONCLUSIONS: Although the indicators of tobacco consumption in KSA are better than most of the countries of the Middle East region and high-income countries, there are many potential areas for improvement. Our findings call for the development and implementation of programs to prevent smoking initiation and encourage quitting. To achieve its health goals, KSA may consider increasing taxation on tobacco products as well as other measures. PMID- 26141061 TI - Genomic copy number variation in Mus musculus. AB - BACKGROUND: Copy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously. RESULTS: We found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR). CONCLUSION: The analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies. PMID- 26141063 TI - Standardization of the methods and reference materials used to assess virus content in varicella vaccines. AB - BACKGROUND: In Korea, every vaccine lot is tested by the National Center for Lot Release (NCLR) in accordance with the national lot release procedures to ensure the safety and efficacy of vaccines. These quality tests examine the virus content in varicella vaccines via plaque assays (either the agar overlay method [AOM] or plaque staining method [PSM]), according to the procedures suggested by the Korean Reference Material for the Varicella Vaccine (KRMVV) or the manufacturer's standard in-house protocol. AIM: To standardize the virus content tests, viral titers in the KRMVV were measured using the PSM at four participating laboratories in a collaborative study. With the aim of developing a standardized method using the KRMVV as a positive control, we compared the ability of the two test methods, AOM and PSM, to accurately and reproducibly determine the virus content of two commercial varicella vaccines. RESULTS: The results showed that the standardized method (PSM) was more suitable for quality control analysis of the varicella vaccine. CONCLUSION: Use of a standardized method (PSM) according to the Korean reference material will improve the reliability and objectivity of lot release testing. PMID- 26141064 TI - A method to investigate the anti-metabolic activity of anti-cancer agents on ovarian cancer cells cultured in a 96-well high throughput format. AB - BACKGROUND: An early step of advanced ovarian cancer begins when floating cancerous cells as single cells or small clusters grow on the peritoneal surface. This surface is rich in extracellular matrix (ECM) proteins, which have profound effects on cellular behaviour and can facilitate cancer progression. Subsequently, this ECM may alter cellular metabolism making cancer cells susceptible to chemotherapeutic agents differently. Therefore, generating a cell culture tool in vitro that includes the interaction between ECM and cancer cells will facilitate our understanding of how cancer cells behave during cancer treatment. There is some evidence to suggest that in an in vitro model that includes ECM components such as collagens will provide a better predictive tool for drug evaluation than a traditional cell monolayer (2D) culture model. FINDINGS: As a proof -of- concept, we made a collagen gel in a 96-well plate format and utilised this to evaluate the efficacy of clinical cytotoxic drugs, a targeted drug, and food compounds in single and combination treatments. The primary endpoints were to measure the reduction of cellular metabolism and secretion of vascular endothelial growth factor (VEGF). The invasive capacity of cancer cells was observed in collagen gels and it was cell line-dependent. The responses to drugs were prominently observed in collagen gels, but they had little effect on 2D cell monolayers. These responses were cell line- and type of drug-dependent. CONCLUSIONS: The collagen gel in a 96 well plate format was easy to set up and could have potential to identify drug sensitivity in the clinical management of women with platinum resistant ovarian cancer. PMID- 26141065 TI - Brain imaging in Kufs disease type B: case reports. AB - BACKGROUND: The clinical traits of Kufs disease (KD) type B (CLN13), an adult onset neuronal ceroid lipofuscinosis (NCL), are well established according to the neurological features of the cases reported with mutations in CTSF. The neuroradiological characteristics of this uncommon disease have not yet been outlined. CASE PRESENTATION: We hereby report the brain MRI features in two Caucasian women who carried homozygous mutations in CTSF, providing a short review of the neuroradiological findings of other common NCLs. Together with a brain volume reduction, the two cases showed white matter hyperintensities and thinning of the corpus callosum at onset of the cognitive decline. CONCLUSION: White matter hyperintensities associated with volume reduction of the corpus callosum may be present at the beginning of the behavioural changes in CLN13 and represent further clues for searching mutations in CTSF. PMID- 26141066 TI - Back to the Future of Genetic Counseling: Commentary on "Psychosocial Genetic Counseling in the Post-Nondirective Era". PMID- 26141067 TI - Genetic Counselors' Experiences with Paternal Involvement in Prenatal Genetic Counseling Sessions: An Exploratory Investigation. AB - Limited research exists concerning male partners' participation in prenatal genetic counseling (R. Kenen, A. C. M. Smith, C. Watkins, & C. Zuber-Pitore, J. Genet Corns 9, 33-45, 2000). To further understand paternal participation, we interviewed 17 experienced prenatal genetic counselors to assess their perspectives on this issue. We investigated 6 research questions: 1) How do genetic counselors define paternal involvement, 2) how do they determine and address problematic involvement, 3) what factors influence involvement, 4) was paternal involvement addressed in training, 5) how might training be improved, and 6) how do participant strategies for addressing involvement compare to those of marriage/family therapists? Qualitative analysis revealed that 1) participants regard paternal involvement asimportant; 2) most address problematic involvement with strategies similar to those of marital/family therapists; 3) influential factors include male partner's characteristics, the couple's relationship (including culturalpractices), and pregnancy factors; and 4) participants received little or notraining on paternal involvement and recommended didactic and experientialactivities. Implications and research recommendations are presented. PMID- 26141069 TI - Genetic Library. PMID- 26141068 TI - Reducing Psychological Distress in a Genetic Counseling Consultation for Breast Cancer. AB - High levels of cancer specific distress have been found before and after genetic counseling for breast cancer. This study investigated the process of reducing distress during 111 genetic counseling consultations for familial breast cancer. Consultations were audiotaped, transcribed, and a detailed coding system developed to measure cues of emotional distress from the patient, and consultant (clinical geneticist or genetic counselor) behaviors before and after the cues. At least 1 emotional cue was given in 64 consultations, with a median of 1 cue per consultation. More emotional cues of distress occurred when the consultant responded empathetically to the first cue of distress. Satisfaction outcomes were largely positive regardless of the consultant's attentiveness to distress. Postconsultation depression scores were significantly reduced if more empathic responses were given, but anxiety remained the same. These results are discussed and recommendations are made for improving patient care. PMID- 26141070 TI - In Memoriam: Sheldon Clark Reed, PhD, 1910-2003. PMID- 26141071 TI - Understanding Language, Hearing Status, and Visual-Spatial Skills. AB - It is frequently assumed that deaf individuals have superior visual-spatial abilities relative to hearing peers and thus, in educational settings, they are often considered visual learners. There is some empirical evidence to support the former assumption, although it is inconsistent, and apparently none to support the latter. Three experiments examined visual-spatial and related cognitive abilities among deaf individuals who varied in their preferred language modality and use of cochlear implants (CIs) and hearing individuals who varied in their sign language skills. Sign language and spoken language assessments accompanied tasks involving visual-spatial processing, working memory, nonverbal logical reasoning, and executive function. Results were consistent with other recent studies indicating no generalized visual-spatial advantage for deaf individuals and suggested that their performance in that domain may be linked to the strength of their preferred language skills regardless of modality. Hearing individuals performed more strongly than deaf individuals on several visual-spatial and self reported executive functioning measures, regardless of sign language skills or use of CIs. Findings are inconsistent with assumptions that deaf individuals are visual learners or are superior to hearing individuals across a broad range of visual-spatial tasks. Further, performance of deaf and hearing individuals on the same visual-spatial tasks was associated with differing cognitive abilities, suggesting that different cognitive processes may be involved in visual-spatial processing in these groups. PMID- 26141072 TI - PiSZ alpha-1 antitrypsin deficiency (AATD): pulmonary phenotype and prognosis relative to PiZZ AATD and PiMM COPD. AB - INTRODUCTION: The PiSZ genotype results in less severe deficiency of alpha-1 antitrypsin (AAT) than PiZZ. Less is known about phenotypic and prognostic features. METHODS: We studied 699 PiZZ, 126 PiSZ and 316 PiMM patients. All AAT deficiency (AATD) patients were augmentation naive. PiSZ were compared with PiZZ patients for clinical phenotype at baseline including CT findings, smoke exposure, progression of lung disease and survival. Similarly, PiSZ patients diagnosed as a result of investigation for possible lung disease (lung index cases) were compared with PiMM. Multivariable analytical techniques and matching (PiSZ to PiZZ) were employed to account for demographic differences. RESULTS: Pack-years smoked and FEV1 exhibited a negative correlation in PiSZ and ZZ patients (both r=-0.43), with emphysema and COPD occurring more commonly in PiZZ patients at <20 pack-year exposure. In multivariable analyses, PiSZ patients were less likely to have emphysema (p<0.01) and had better survival than PiZZ (p=0.017), but lung function decline did not differ significantly. 42% of PiSZ patients had upper-zone-dominant emphysema on CT scan. Analyses of AAT level confirmed a critical threshold at 11 MUM, particularly with regard to phenotypes classical of PiZZ AATD.Significant baseline differences suggested that PiSZ had presented earlier to health services than PiMM. Once this was accounted for, risk of emphysema did not differ between PiSZ and PiMM although survival was lower in PiMM patients (p<0.01). CONCLUSIONS: PiSZ patients are less susceptible to cigarette smoke than PiZZ. The pattern of emphysema may be similar at diagnosis to usual COPD. PMID- 26141073 TI - Gene therapy trial for cystic fibrosis shows modest benefits. PMID- 26141074 TI - Disruption of thalamic connectivity in Alzheimer's disease: a diffusion tensor imaging study. AB - The aim of this study was to evaluate the structural integrity of the thalamic connectivity of specific fiber tracts in different stages of Alzheimer's disease (AD) using diffusion tensor imaging (DTI). Thirty-five patients with AD and 22 normal control (NC) subjects were recruited. Based on Mini Mental State Examination score, the AD patients were divided into three subgroups for comparison with the NC group: mild (mi-AD, n = 14), moderate (mo-AD, n = 12), and severe (se-AD, n = 9) AD. The fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR) were selected to represent the thalamic connectivity with other brain regions. The fornix was divided into the column and body of the fornix (FX-1) and the bilateral fornix (crus)/stria terminalis (FX 2/ST) based on the atlas. Through the atlas-based analysis and fiber tracking method, we measured fractional anisotropy (FA), mean diffusivity (MD), and tract volume to reflect the microstructural and macrostructural changes of these fibers during AD progression. There were significant differences in the FA and MD of all fibers, except the right PTR, between the AD and NC subjects. Further subgroup analyses revealed that the mi-AD subgroup had decreased FA only in the FX-1 and increased MD in the FX-1 and bilateral ATR, the mo-AD subgroup showed declined FA and increased MD in the FX-1, bilateral FX-2/ST and ATR; the se-AD subgroup exhibited lower FA and higher MD values in all fibers except the right PTR. We also found reduced tract volume values in the FX and left ATR in the AD patients. Further subgroup analyses revealed that these differences only existed in the se AD patients. Our DTI analyses indicate that the integrity of thalamic connectivity is progressively disrupted following cognitive decline in AD and that DTI parameters in the column and body of the fornix show promise as potential markers for the early diagnosis of AD and for monitoring disease progression. PMID- 26141075 TI - Risk Factors for Adverse Outcomes in Patients Hospitalized With Lower Gastrointestinal Bleeding. AB - OBJECTIVE: To determine which risk factors and subtypes of lower gastrointestinal bleeding (LGIB) are associated with adverse outcomes after hospital discharge (30 day readmissions, recurrent LGIB, and death). PATIENTS AND METHODS: We conducted a prospective observational study of consecutive patients admitted with LGIB to Beth Israel Deaconess Medical Center from April 1, 2013, through March 30, 2014. Patients were contacted 30 days after discharge to determine hospital readmissions, recurrent LGIB, and death. Multivariable Cox proportional hazards regression models were used to describe associations of variables with 30-day readmissions or recurrent LGIB. Logistic regression was used to determine association with mortality. RESULTS: There were 277 patients hospitalized with LGIB. Of the 271 patients surviving to discharge, 21% (n=57) were readmitted within 30 days, 21 of whom were admitted for recurrent LGIB. The following factors were associated with 30-day readmissions: developing in-hospital LGIB (hazard ratio [HR], 2.26; 95% CI, 1.08-4.28), anticoagulation (HR, 1.82; 95% CI, 1.05-3.10), and active malignancy (HR, 2.33; 95% CI, 1.11-4.42). Patients discharged while taking anticoagulants had higher rates of recurrent bleeding (HR, 2.93; 95% CI, 1.15-6.95). Patients with higher Charlson Comorbidity Index scores (odds ratio [OR], 1.57; 95% CI, 1.25-2.08), active malignancy (OR, 6.57; 95% CI, 1.28-28.7), and in-hospital LGIB (OR, 11.5; 95% CI, 2.56-52.0) had increased 30-day mortality risk. CONCLUSION: In-hospital LGIB, anticoagulation, and active malignancy are risk factors for 30-day readmissions in patients hospitalized with LGIB. In-hospital LGIB, Charlson Comorbidity Index scores, and active malignancy are risk factors for 30-day mortality. PMID- 26141076 TI - A non-invasive prevention program model for the assessment of osteoporosis in the early postmenopausal period: a pilot study on FRAX((r)) and QUS tools advantages. AB - OBJECTIVE: The study analyses the performances of FRAX algorithm and quantitative ultrasound (QUS) tool in relationship to the dual-energy X-ray absorptiometry (DXA) categorization to identify patients at risk of osteoporosis during menopause and to reach new thresholds for recommending the first DXA examination. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Two hundred eighty two postmenopausal patients filled out a questionnaire which determined their FRAX index and performed a bone evaluation by QUS of the calcaneus to determine their stiffness index (SI). Thereafter, they underwent assessments by the gold standard DXA bone examination. RESULTS: Statistically significant correlations were observed between FRAX (calculated without BMD) and both QUS and DXA diagnosis. FRAX mean indices of risk corresponding to the diagnosis of osteoporosis by QUS and DXA were similar. Receiver operating characteristic (ROC) curve analysis showed that both FRAX and QUS tests were sufficiently accurate in predicting the alteration of bone mineral composition. The ROC curves of QUS allowed us to identify, in our population, SI cutoff for normal patients (SI > 90.5) and for patients having osteoporosis (SI < 78.5). We selected a cutoff screening value from FRAX ROC curve for major clinical fracture (2.94). The following diagnostic algorithm demonstrated that the use of FRAX test alone has a sensitivity of 85.3 % and a specificity of 33.8 % while the use of QUS exam alone showed a sensitivity of 81.3 % and a specificity of 45.1 %. When considering the capacity of QUS exam in combination with FRAX test, the final algorithm showed a sensitivity of 69.4 % and a specificity of 57.7 %. CONCLUSIONS: The use of QUS test with adjusted cutoffs offers a similar performance to the FRAX test alone in terms of sensitivity. The combined use of the tests reduces the sensibility but increases the specificity and adds clinical information related to the bone status of the patient. PMID- 26141077 TI - The effectiveness of noninvasive interventions for musculoskeletal thoracic spine and chest wall pain: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration. AB - OBJECTIVE: The purpose of this study was to critically appraise and synthesize evidence on the effectiveness of noninvasive interventions, excluding pharmacological treatments, for musculoskeletal thoracic pain. METHODS: Randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effectiveness of noninvasive interventions were eligible. We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials accessed through Ovid Technologies, Inc, and CINAHL Plus with Full Text accessed through EBSCOhost from 1990 to 2015. Our search strategies combined controlled vocabulary relevant to each database (eg, MeSH for MEDLINE) and text words relevant to our research question and the inclusion criteria. Random pairs of independent reviewers screened studies for relevance and critically appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a low risk of bias were synthesized following best evidence synthesis principles. RESULTS: We screened 6988 articles and critically appraised 2 studies. Both studies had a low risk of bias and were included in our synthesis. One RCT compared thoracic spinal manipulation, needle acupuncture, and placebo electrotherapy for recent thoracic spine pain. There were statistically significant but clinically nonimportant short-term reductions in pain favoring manipulation. There were no differences between acupuncture and placebo electrotherapy. Another RCT compared a multimodal program of care and a session of education for recent musculoskeletal chest wall pain. The multimodal care resulted in statistically significant but clinically nonimportant short-term reductions in pain over education. However, participants receiving multimodal care were more likely to report important improvements in chest pain. CONCLUSIONS: Quality evidence on the management of musculoskeletal thoracic pain is sparse. The current evidence suggests that compared to placebo, spinal manipulation is associated with a small and clinically nonimportant reduction in pain intensity and that acupuncture leads to similar outcomes as placebo. Furthermore, a multimodal program of care (ie, manual therapy, soft tissue therapy, exercises, heat/ice, and advice) and a single education session lead to similar pain reduction for recent-onset musculoskeletal chest wall pain. However, patients who receive multimodal care are more likely to report pain improvements. PMID- 26141079 TI - Editorial Introduction. PMID- 26141080 TI - 1999 Presidential Address to the National Society of Genetic Counselors. PMID- 26141081 TI - New Diplomates of the American Board of Genetic Counseling-1999. PMID- 26141078 TI - Mechanotransduction: use the force(s). AB - Mechanotransduction - how cells sense physical forces and translate them into biochemical and biological responses - is a vibrant and rapidly-progressing field, and is important for a broad range of biological phenomena. This forum explores the role of mechanotransduction in a variety of cellular activities and highlights intriguing questions that deserve further attention. PMID- 26141082 TI - Psychological Model for Presymptomatic Test Interviews: Lessons Learned from Huntington Disease. AB - This paper reflects on experience gained from presymptomatic testing for Huntington disease. An approach is presented which considers the role of the clinician and aims of the interview. Irrespective of the disease being tested for, it is suggested that the psychological aim of presymptomatic testing is to foster emotional insight and understanding that will help clients in their decision-making process about testing and their subsequent adjustment to the result. Based on these aims the process of presymptomatic testing, counseling is considered in terms of clarification, consideration, education, and reflection, followed by decision making. Practical approaches are discussed and illustrated with clinical examples. PMID- 26141083 TI - To Use or Not to Use: Male Partners' Perspectives on Decision Making About Prenatal Diagnosis. AB - We conducted an exploratory, qualitative pilot study investigating the use of genetic counseling and prenatal genetic technologies between women and their male partners for two referral groups: pregnant women 35 years of age and over (AMA) at the time of delivery and pregnant women with an abnormal maternal serum triple screen (MSAFP3). The convenience sample consisted of 25 semistructured interviews and 50 observations of genetic counseling sessions. Male partners' styles of decision making and the way they viewed prenatal diagnosis decision making were examined. We defined three decision-making styles based on our interpretation of the data: (1) domain, (2) joint-delegated, and (3) saliency. The male partners also seemed to view prenatal diagnosis as either an information decision or an action decision and appeared to take a more active role in decision making when the decision was viewed as an action decision. PMID- 26141084 TI - Counseling Assessment and Skills: Introduction to the New Section. PMID- 26141085 TI - Recommendations for Telephone Counseling. AB - Telephone counseling can provide a convenient, accessible, and valuable source of information to the general public, health care providers, and other professionals. In the genetic counseling profession, telephone counseling is often associated with teratogen information services. However, genetic counselors routinely utilize the telephone in a number of different counseling encounters. Nevertheless, the literature provides very little guidance to how that encounter might be conducted, what information should be obtained and provided, or how the encounter should be documented. We present a brief overview of the history of telephone counseling, a description of the major differences between telephone counseling and a face-to-face counseling session, and a framework to optimize a telephone counseling session. PMID- 26141086 TI - Commentary: What Is and Is Not Telephone Counseling? PMID- 26141087 TI - Genetic Library. PMID- 26141088 TI - Leisure-Time Physical Activity in adults with Cerebral Palsy. AB - BACKGROUND: Cerebral Palsy (CP) is becoming more prevalent in the adult population, but there is limited information available regarding their Leisure Time Physical Activity (LTPA). OBJECTIVE: To investigate the self-reported frequency and LTPA participation patterns in adults with CP, compared to the Canadian general population (CGP). METHODS: This was a cross-sectional, follow-up survey of a cohort of 145 persons with CP. The primary outcome was the level of participation in LTPA. Questions were also posed about the motivations and self reported barriers to LTPA participation. The survey results were compared to CGP estimates from the Canadian Community Health Survey (CCHS). RESULTS: Fifty-four participants completed the survey, and 90% reported participation in at least one LTPA per week. On average, they reported participating in LTPA 7.3 +/- 5.7 times/week. They also reported participating in an average of 4.1 +/- 2.4 different types of LTPA. Walking, home-exercise, and swimming were the most frequently reported as a primary LTPA in the CP sample. These finding were comparable to those from the CGP. However, adults with CP were more likely to participate in home-exercise than the CGP (p < 0.05). More than 40% reported that the purpose of their LTPA was fitness or body maintenance and 56% indicated an interest in starting new activities. Various barriers were also reported. CONCLUSIONS: Adults with CP frequently participated in LTPA. However, the majority of them are not achieving recommended daily physical activity levels. Also their LTPA habitually focuses on rehabilitative exercises and the diversity of LTPA is limited by several barriers. PMID- 26141089 TI - A severe case of bowel impaction. PMID- 26141091 TI - Daytime napping results in an underestimation of thermal strain during exercise in the heat. PMID- 26141090 TI - Outcomes of ultra-low anterior resection combined with or without intersphincteric resection in lower rectal cancer patients. AB - PURPOSE: We evaluated the current practice of ultra-low anterior resection (uLAR) in patients with lower rectal cancer and compared uLARs using mostly transabdominal approach with or without intersphincteric resection (ISR). METHODS: A total of 624 consecutive lower rectal cancer patients undergoing curative uLAR were prospectively enrolled as ISR+ vs. ISR- groups (329 vs. 295 patients) between 2005 and 2012. The ISR+ group additionally received levator sphincter reinforcement after distal resection. RESULTS: The circumferential resection margin (CRM) + rate (<=1 mm) was 2.1 % in the two groups. Postoperative ileus occurred more in the ISR- group than in the ISR+ group (p = 0.02). Substantial erectile dysfunction occurred 1.8 times more frequently in the ISR- group than in the ISR+ group (32 vs. 18.1 %; p = 0.01) among male patients at 2 years postoperatively. The urge to defecate volume and maximal tolerance volume, closely correlated with maximal squeezing pressure and/or mean resting pressure, did not differ between patients with and without chemoradiotherapy until 24 months postoperatively. Nevertheless, the urge to defecate volume was lesser in the ISR- group than in the ISR+ group at 24 months postoperatively (p = 0.022). For 301 patients in which >5 years had elapsed postoperatively, the mean 5-year local recurrence rate was 4.3 %, and the 5-year disease-free and overall survival rates were 78.9 and 92 %, respectively, without differences between the two groups. CONCLUSIONS: Compared with uLAR without ISR, the transabdominal ISR with levator-sphincter reinforcement provides a safe resection plane with competent CRM, concurrently reduces substantial complications, and marginally promotes recovery of neorectal function. PMID- 26141093 TI - Introduction. PMID- 26141092 TI - Impact of Climate Change on Air Quality and Public Health in Urban Areas. AB - This review discusses how climate undergo changes and the effect of climate change on air quality as well as public health. It also covers the inter relationship between climate and air quality. The air quality discussed here are in relation to the 5 criteria pollutants; ozone (O3), carbon dioxide (CO2), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter (PM). Urban air pollution is the main concern due to higher anthropogenic activities in urban areas. The implications on health are also discussed. Mitigating measures are presented with the final conclusion. PMID- 26141094 TI - An Assessment of Ethnocultural Beliefs Regarding the Causes of Birth Defects and Genetic Disorders. AB - With the expansion of genetic services to various cultural groups, genetic counselors encounter clients who hold diverse beliefs inscribed by their culture about health conditions. Thus, clients may attribute the cause of a birth defect or genetic condition to a culturally-based health belief. This present study was conducted as a pilot study in order to assess the beliefs about the causes of birth defects and genetic disorders held by women of different ethnocultural backgrounds. This study proposed that women who do not have a family history of a disorder will differ in their knowledge about the cause of a birth defect or genetic disorder compared to women who have an affected child. In addition, this study determined to what extent culturally-based health beliefs are attributed to being the cause of a birth defect or genetic disorder in the 1990s. PMID- 26141095 TI - Acculturation in Women with Mental Retardation and Its Impact on Genetic Counseling. AB - The provision of genetic counseling to women with mild mental retardation poses many challenges, some directly related to their developmental and cognitive disabilities. Traditional genetic counseling models, in which decision-making is largely based on the understanding of factual information, are particularly affected by the intellectual limitations which characterize this population. Equally important, however, are these women's attitudes, perceptions, and behaviors related to their involuntary inclusion into a highly stigmatized social group. Common themes among these women which surface in the genetic counseling setting include the denial of mental retardation, a hierarchical perception of their own and others' disabilities, and a strong motivation to conceive and parent a child. Such attitudes and behaviors may be symptomatic of acculturation, as these women struggle to take on accepted social roles while rejecting the stigma of intellectual disability. In contrast to factual information, the counselee's ability to discuss emotions and perceptions is not necessarily hampered by her intellectual limitations. A focus on the recognition and discussion of psychosocial issues provides a more meaningful approach than traditional genetic counseling models for facilitating informed reproductive decisions among women with mental retardation. PMID- 26141096 TI - Reproductive Genetic Counseling to Asian-Pacific and Latin American Immigrants. AB - Latin and Asian-Pacific immigrants are the fastest growing new-comer groups in the U.S. contributing to 85% of immigration totals. New immigrants experience multiple barriers to accessing genetic counseling resulting from cultural, linguistic, financial, and educational factors as well as having unique perceptions on health, illness, reproduction, and life as a whole. In addition, new immigrants lack familiarity with Western medical practices as well as genetic risk and available interventions. We provided perinatal genetic services to 2430 clients, mostly new immigrants of Latin and Asian-Pacific descent over a period of 6 years. Counseling aides sharing the clients' cultural backgrounds were employed. A study assessing the efficacy of cross-cultural education regarding advanced maternal age risk and amniocentesis was implemented and linked to a database containing demographic and clinical information. Practical observations relating to cultural beliefs in the two groups relevant to perinatal genetic counseling were made. PMID- 26141097 TI - Preconception Genetic Counseling: Three Years of Experience at a Community-Based Health Center. AB - In the United States, access to genetic education and services is not equally available to all segments of the population, especially to women of minority backgrounds and low incomes. In response to this issue, the Preconception Genetic Health Education Program (PGHEP) was implemented in September of 1993 at the Woodlawn Maternal and Child Health Center in south side Chicago. The goal of this program is to provide access to genetic services to a previously underserved population. Women attending the family planning clinics are offered free, confidential preconception genetic screening and counseling on-site. As of January 1, 1997, 1300 women have participated in the program. The development and implementation of the PGHEP, client self-reports of family histories and beliefs, and implications for future delivery of genetic services are discussed. PMID- 26141098 TI - Curriculum Evaluation and Assessment of Multicultural Genetic Counselor Education. AB - Multicultural competence in genetic counseling integrates racial-cultural knowledge, awareness, and skills into clinical interventions and research practices. Researchers and educators often cite racial-cultural factors as obstacles for visible racial-cultural people seeking help. However, the professional's unfamiliarity of how his or her own racial-cultural group affiliations are influenced by the history of discrimination and oppression coupled with their lack of self-understanding of racial-cultural issues for him- or herself has also limited the effectiveness of genetic counseling. The purpose of this study is to evaluate the effectiveness of the Handbook of Cross-Cultural Genetic Counseling, a multicultural curriculum developed for genetic counselor education for increasing multicultural counseling competence. The multicultural curriculum was evaluated for its effectiveness of increasing multicultural counseling competence using a nonequivalent control group design. A participant's multicultural counseling competence was hypothesized to increase after being taught the curriculum. The curriculum was effective for increasing multicultural counseling competence. Additionally, achieved multicultural counseling competence was not influenced by when the curriculum was taught. Trend analyses measuring the longitudinal impact of the curriculum on multicultural competence were significant. Implications of the results are discussed. PMID- 26141099 TI - Genetic Library. PMID- 26141100 TI - An"ON-OFF" switchable power output of enzymatic biofuel cell controlled by thermal-sensitive polymer. AB - A novel "ON-OFF" switchable enzymatic biofuel cell (EBFC), controlled by in situ thermal-stimuli signal, has been consciously designed. Poly (N isopropylacrylamide) (PNIPAm) chains were used to act as "ON" and "OFF" channels. Consecutively switching of temperature below and above the lower critical solution temperature (LCST), the reversible conformation changing of the PNIPAm chains between superhydrophilicity and superhydrophobicity was achieved, which constructed the "ON" and "OFF" channel for the transfer of the electrochemical probe to the underlying electrode correspondingly. Gold nanoparticles (AuNPs) protected glucose oxidase and laccase were successfully entrapped into the intelligent thermal-sensitive PNIPAm chains, and performed as the catalysts for the oxidation of glucose and the reduction of O2, respectively. Below the LCST, the fuels and the mediator could access to the catalytic centers of enzymes (set as "ON" state); while above the LCST, the reaction was impeded because the process of reactant transmission was blocked (set as "OFF" state). By switching the "valve" of mass transfer, the fabricated EBFC displayed the obvious "ON-OFF" controllable behavior. At the "ON" state, the open circuit voltage (Ecell(ocv)) and maximal power output density (Pmax) could reach to 0.70 V and 20.52 MUW cm( 2), respectively; while at the "OFF" state, the Ecell(ocv) and Pmax were only 0.30 V and 3.28 MUW cm(-2) correspondingly. The switchable process was repeatable, and the response time was only several minutes. PMID- 26141101 TI - A near-infrared ratiometric fluorescent probe for cysteine detection over glutathione indicating mitochondrial oxidative stress in vivo. AB - We establish a near-infrared (NIR) ratiometric fluorescent probe Cy-NB for the selective detection of cysteine (Cys) over glutathione (GSH) and homocysteine (Hcy) in mitochondria to indicate oxidative stress. Heptamethine cyanine dye is chosen as the fluorophore of Cy-NB whose emission locates in NIR region. And p nitrobenzoyl is employed as the fluorescent modulator due to its capability of selective-Cys response. Once triggered by Cys, the uncaged p-nitrobenzoyl rearranges the polymethine pi-electron system of the fluorophore, which leads to a remarkable spectrum shifts in absorption and emission profiles. Taking advantage of these spectroscopic properties, we construct a ratiometric fluorescent signal for the detection of Cys with a detection limit of 0.2 uM within 5 min. Our probe Cy-NB can sensitively detect the mitochondrial Cys pool changes under different oxidative stress status in HepG2 cells. We also successfully employ Cy-NB to imaging Cys level changes in living mice. It suggests that mitochondrial Cys can be used as an oxidative stress biomarker with simple potential clinical applications. And our probe Cy-NB is of great potential for further utilizing in exploring the physiological function of Cys in biological systems. PMID- 26141102 TI - Gold nanoprobes-based resonance Rayleigh scattering assay platform: Sensitive cytosensing of breast cancer cells and facile monitoring of folate receptor expression. AB - A rapid, facile assay for sensitive cytosensing of breast cancer cells should help to guide potential medical evaluation for breast cancer. Here, we report development of novel resonance Rayleigh scattering (RRS) cytosensor for cell recognitions and folate (FA) receptor expression analyses on living cells. Using FA-conjugated gold nanoparticles (FA-AuNPs) as nanoprobes, the constructed nanoprobes-assembled recognition interface could increase the binding capacity for cell recognition, amplify Au-aggregates-enhanced RRS signal, and then enhance the sensitivity for membrane antibody assay. FA-AuNPs-based RRS measurements enabled a distinct 34-times-enhancement in RRS intensities after incubation with human breast cancer cells, compared with normal cells. Receptor-targeted cytosensor was used to quantitatively detect human breast cancer MCF-7, liver cancer HepG2 and normal cells, which expressing different amount of FA receptor, respectively. The detection limit for MCF-7 cells was 12 cells/mL with good selectivity and reproducibility. Furthermore, the proposed cytosensor allowed for dynamic evaluation of FA receptor expression on different living cells after dihydroartemisinin stimulus. This assay platform shows the good potential for clinical diagnostics and antibody-targeted drug screening. PMID- 26141103 TI - A multicolor time-resolved fluorescence aptasensor for the simultaneous detection of multiplex Staphylococcus aureus enterotoxins in the milk. AB - Food safety is one of the most important public health issues worldwide. Foodborne illnesses caused by Staphylococcus aureus enterotoxins (SEs) commonly occur, affecting both developing and developed countries. In this study, multicolor lanthanide-doped time-resolved fluorescence nanoparticles labeled with aptamers were used as bioprobes, and graphene oxide (GO) was employed as a resonance energy acceptor. Based on the "turn down" strategy, the simultaneous detection of multiplex SEs was realized in a homogeneous solution. Under the optimal conditions, the developed method exhibited high sensitivity and selectivity to three serological types of enterotoxins, including type A, B, C1, with limits of detection below 1 ng mL(-1). The application of this bioassay in milk analysis with no sample dilution was also investigated, and the results of recovery rates covered from 92.76% to 114.58%, revealing that the developed method was accurate. Therefore, this detection aptasnesor can be a good candidate for multiplex analysis and screening with simple and effective operations. PMID- 26141104 TI - Gold nanoclusters-Cu(2+) ensemble-based fluorescence turn-on and real-time assay for acetylcholinesterase activity and inhibitor screening. AB - Based on the specific binding of Cu(2+) ions to the 11-mercaptoundecanoic acid (11-MUA)-protected AuNCs with intense orange-red emission, we have proposed and constructed a novel fluorescent nanomaterials-metal ions ensemble at a nonfluorescence off-state. Subsequently, an AuNCs@11-MUA-Cu(2+) ensemble-based fluorescent chemosensor, which is amenable to convenient, sensitive, selective, turn-on and real-time assay of acetylcholinesterase (AChE), could be developed by using acetylthiocholine (ATCh) as the substrate. Herein, the sensing ensemble solution exhibits a marvelous fluorescent enhancement in the presence of AChE and ATCh, where AChE hydrolyzes its active substrate ATCh into thiocholine (TCh), and then TCh captures Cu(2+) from the ensemble, accompanied by the conversion from fluorescence off-state to on-state of the AuNCs. The AChE activity could be detected less than 0.05 mU/mL within a good linear range from 0.05 to 2.5 mU/mL. Our proposed fluorescence assay can be utilized to evaluate the AChE activity quantitatively in real biological sample, and furthermore to screen the inhibitor of AChE. As far as we know, the present study has reported the first analytical proposal for sensing AChE activity in real time by using a fluorescent nanomaterials-Cu(2+) ensemble or focusing on the Cu(2+)-triggered fluorescence quenching/recovery. This strategy paves a new avenue for exploring the biosensing applications of fluorescent AuNCs, and presents the prospect of AuNCs@11-MUA Cu(2+) ensemble as versatile enzyme activity assay platforms by means of other appropriate substrates/analytes. PMID- 26141105 TI - Mass effect of redox reactions: A novel mode for surface plasmon resonance-based bioanalysis. AB - The pursuit of more specific and sensitive response is a perpetual goal for modern bioassays. This work proposed a novel label-free strategy about redox related mass effect based on the surface plasmon resonance (SPR) technique for ultrasensitive determination of DNA. The protocol starts with the modification of SPR gilded disk with the capture DNA (cDNA). After the conjugation of immobilized cDNA with the target DNA (tDNA), the hybridization chain reaction was triggered by the introduction of mutual partial complementary primers to elongate the terminal into a nanoscale duplex. As it is reported that porphyrin could intercalate into the grooves of the double-stranded DNA (dsDNA) scaffold, multiple positive-charged Fe(III)meso-tetra(N-methyl-4-pyridyl) porphine (FeTMPyP) with symmetric structure were uptaken for in situ formation of porphyrin-dsDNA complex. Given FeTMPyP a highly efficient catalysis for the peroxide reduction, its presence as a biomimetic cofactor was validated via circular dichroism and UV-vis spectroscopy, demonstrating a tight binding as well as high catalytic activity and stability. Using 4-chloro-1-naphthol as a proton donor, the catalytic reduction of H2O2 would oxidize it into insoluble benzo-4 chloro-hexadienone, which simultaneously deposited on the heterogeneous interface, leading to a significant amplification in both SPR response and topological height profile. The signal increment was proportional to the concentration of tDNA, thus an ultrasensitive SPR-based DNA assay was developed with a linear range over four orders of magnitudes and a sub-femtomolar detection limit of 0.73 fM. The developed methodology exemplifies a different way of thinking about mass-sensing modes, extending conventional SPR-based DNA analysis to relevant biomedical applications. PMID- 26141106 TI - [Spleen-preserving surgery after blunt abdominal trauma with splenic hilum involvement]. AB - BACKGROUND: Splenic involvement secondary to blunt abdominal trauma is often treated by performing a splenectomy. The severity of the post-splenectomy syndrome is currently well known (blood loss, sepsis), so there is an increasing tendency to preserve the spleen. The case is presented of splenic preservation after blunt abdominal trauma with hilum involvement, emphasising the role of Floseal as a haemostatic agent, as well as the use of resorbable meshes to preserve the spleen. CLINICAL CASE: A 22-year-old woman presenting with a grade IV splenic lesion secondary to a blunt abdominal trauma after a traffic accident. Partial splenic resection was performed and bleeding was controlled with Floseal and use of a reinforcing polyglycolic acid mesh. No postoperative complications occurred, being discharged on day 5. The long-term follow-up has been uneventful. CONCLUSION: The use of haemostatic agents such as thrombin and the gelatine gel (FloSeal) and the use of polyglycolic acid meshes enable spleen-preserving surgery, making it a feasible and reproducible procedure and an alternative to classical splenectomy. PMID- 26141107 TI - [Subclinical sensorineural hearing loss in female patients with rheumatoid arthritis]. AB - BACKGROUND: The rheumatoid arthritis is a clinical entity capable to cause hearing impairment that can be diagnosed promptly with high frequencies audiometry. OBJECTIVE: To detect subclinical sensorineural hearing loss in patients with rheumatoid arthritis. MATERIAL AND METHODS: Cross-sectional study on patients with rheumatoid arthritis performing high frequency audiometry 125Hz to 16,000Hz and tympanometry. The results were correlated with markers of disease activity and response to therapy. RESULTS: High frequency audiometry was performed in 117 female patients aged from 19 to 65 years. Sensorineural hearing loss was observed at a sensitivity of pure tones from 125 to 8,000 Hz in 43.59%, a tone threshold of 10,000 to 16,000Hz in 94.02% patients in the right ear and in 95.73% in the left ear. Hearing was normal in 8 (6.84%) patients. Hearing loss was observed in 109 (93.16%), and was asymmetric in 36 (30.77%), symmetric in 73 (62.37%), bilateral in 107 (91.45%), unilateral in 2 (1.71%), and no conduction and/or mixed hearing loss was encountered. Eight (6.83%) patients presented vertigo, 24 (20.51%) tinnitus. Tympanogram type A presented in 88.90% in the right ear and 91.46% in the left ear, with 5.98 to 10.25% type As. Stapedius reflex was present in 75.3 to 85.2%. Speech discrimination in the left ear was significantly different (p = 0.02)in the group older than 50 years. No association was found regarding markers of disease activity, but there was an association with the onset of rheumatoid arthritis disease. CONCLUSIONS: Patients with rheumatoid arthritis had a high prevalence of sensorineural hearing loss for high and very high frequencies. PMID- 26141108 TI - [Sentinel lymph node biopsy in melanoma: our experience over 8 years in a universitary hospital]. AB - BACKGROUND: Since the introduction of sentinel lymph node biopsy, its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. Our experience of sentinel lymph node biopsy for melanoma is presented and evaluated. MATERIAL AND METHODS: A cohort study was conducted on 69 patients with a primary cutaneous melanoma and with no clinical evidence of metastasis, who had sentinel lymph node biopsy from October-2005 to December 2013. Sentinel lymph node biopsy was identified using preoperative lymphoscintigraphy and subsequent intraoperative detection with gamma probe. RESULTS: The sentinel lymph node biopsy identification rate was 98.5%. The sentinel lymph node biopsy was positive for metastases in 23 patients (33.8%). Postoperative complications after sentinel lymph node biopsy were observed in 4.4% compared to 38% of complications in patients who had complete lymphadenectomy. CONCLUSION: The sentinel lymph node biopsy in melanoma offers useful information about the lymphatic dissemination of melanoma and allows an approximation to the regional staging, sparing the secondary effects of lymphadenectomy. More studies with larger number of patients and long term follow up will be necessary to confirm the validity of sentinel lymph node biopsy in melanoma patients, and especially of lymphadenectomy in patients with positive sentinel lymph node biopsy. PMID- 26141109 TI - [Pylephlebitis: a rare but possible complication of intra-abdominal infections]. AB - BACKGROUND: Pylephlebitis or septic thrombophlebitis of the portal venous system is a rare but serious complication of intra-abdominal infections which drain into the portal venous system. Its diagnosis is based on clinical suspicion and imaging tests, mainly a computed tomography scan, given the lack of specificity of the signs and symptoms. Spread of septic emboli is the major cause of morbidity and mortality. The aim of the study was to analyse patients diagnosed in our hospital. MATERIAL AND METHODS: Retrospective descriptive study of patients diagnosed with pylephlebitis in our hospital. CLINICAL CASES: Four patients were included, 3 men and one woman. In 3 cases it was acute cholecystitis that led to the diagnosis of pylephlebitis at the same time as the intra-abdominal infection. Emergency surgery was performed in one case, whilst the other 2 were treated conservatively. Blood cultures were performed in all cases, and empirical antibiotic treatment was used. In the only case of acute appendicitis, diagnosis of pylephlebitis was achieved during the study of postoperative fever, with empirical antibiotic treatment also being started. The haematologist was requested to start the required anticoagulation therapy in all cases. CONCLUSIONS: Pylephlebitis is a rare complication of intra-abdominal infections that may make lead to a worse outcome. A high level of suspicion is required as well as imaging tests to make an early diagnosis and appropriate treatment. PMID- 26141110 TI - [Partial stomach partitioning gastrojejunostomy in the treatment of the malignant gastric outlet obstruction]. AB - BACKGROUND: In patients with unresectable gastric cancer and outlet obstruction syndrome, gastric partitioning gastrojejunostomy is an alternative, which could avoid the drawbacks of the standard techniques. OBJECTIVE: Comparison of antroduodenal stent, conventional gastrojejunostomy and gastric partitioning gastrojejunostomy. MATERIAL AND METHODS: A retrospective, cross-sectional study was conducted on patients with unresectable distal gastric cancer and gastric outlet obstruction, treated with the three different techniques over the last 12 years, comparing results based on oral tolerance and complications. An analysis was performed on the results using the Student-t test for independent variables. RESULTS: The 22 patients were divided in 3 groups: group I (6 cases) stent, group II (9 cases) conventional gastrojejunostomy, and group III (7 cases) gastric partitioning gastrojejunostomy, respectively. The stent allows a shorter "postoperative" stay and early onset of oral tolerance (P<0.05), however, the gastric partitioning gastrojejunostomy achieve normal diet at 15th day (P<0.05). The mortality rate was higher in the stent group (33%) compared with surgical techniques, with a morbidity of 4/6 (66.7%) in Group I, 6/9 (66.7%) Group II, and 3/7 (42%) Group III. Re-interventions: 2/6 Group I, 3/9 Group II, and 0/7 Group III. The median survival was superior in the gastric partitioning gastrojejunostomy, achieving an overall survival of 6.5 months. CONCLUSIONS: The gastric partitioning gastrojejunostomy for treatment of gastric outlet obstruction in unresectable advanced gastric cancer is a safe technique, allowing a more complete diet with lower morbidity and improved survival. PMID- 26141112 TI - How active are people in metropolitan parks? An observational study of park visitation in Australia. AB - BACKGROUND: Parks are generally an under-utilized resource in the community with great potential to enhance levels of physical activity. If parks are to attract more visitors across a broad cross-section of the population and facilitate increased physical activity, research is needed to better understand park visitor characteristics and how visitors spend their time in parks. The Recording and EValuating Activity in a Modified Park (REVAMP) study is a natural experiment monitoring a park upgrade in a low socioeconomic status (SES) neighborhood. This study described the observed baseline characteristics of park visitors (age, sex) and characteristics of visitation (weekday or weekend day, period of the day) and explored how these characteristics were associated with observed park-based physical activity in two metropolitan parks located Melbourne, Australia. METHODS: Direct observations of park visitors were conducted using a modified version of SOPARC (the System for Observing Play and Recreation in Communities) on four weekdays and four weekend days. During weekdays, observations were conducted every hour from 7:30 am-4:30 pm and on weekend days from 8:30 am-4:30 pm. This equated to a total of 1460 scans across the two parks. Chi-square tests examined bivariate associations between park-based physical activity, and socio demographic and park visitation characteristics. Logistic regression models examined the odds of being observed engaging in moderate- to vigorous-intensity physical activity relative to lying/sitting/standing according to socio demographic and park visitation characteristics. RESULTS: In total, 4756 park visitors were observed with the majority visiting on weekend days (87 %) and in the afternoon (41 %). Most visitors (62 %) were lying, sitting or standing, with only 29 % observed engaging in moderate-intensity and 9 % in vigorous-intensity physical activity. Park use differed by time of day, sex, age group, and neighborhood SES. Physical activity was lower for women than men (OR 0.76) and higher among visitors in the high SES area (OR 1.52). CONCLUSIONS: Parks offer substantial opportunities for people of all ages to engage in physical activity; however, this study showed that a large proportion of the park visitors observed were engaged in sedentary pursuits. Further research on how park design, amenities and programming can optimize park visitation and park-based physical activity is needed. TRIAL REGISTRATION: Current controlled trial ISRCTN50745547 , registration date 11.1.2014. PMID- 26141113 TI - Simultaneous discrimination of species and strains in Lactobacillus rhamnosus using species-specific PCR combined with multiplex mini-sequencing technology. AB - This study described the use of species-specific PCR in combination with SNaPshot mini-sequencing to achieve species identification and strain differentiation in Lactobacillus rhamnosus. To develop species-specific PCR and strain subtyping primers, the dnaJ gene was used as a target, and its corresponding sequences were analyzed both in Lb. rhamnosus and in a subset of its phylogenetically closest species. The results indicated that the species-specific primer pair was indeed specific for Lb. rhamnosus, and the mini-sequencing assay was able to unambiguously distinguish Lb. rhamnosus strains into different haplotypes. In conclusion, we have successfully developed a rapid, accurate and cost-effective assay for inter- and intraspecies discrimination of Lb. rhamnosus, which can be applied to achieve efficient quality control of probiotic products. PMID- 26141111 TI - Transcriptional response of Atlantic salmon families to Piscirickettsia salmonis infection highlights the relevance of the iron-deprivation defence system. AB - BACKGROUND: Piscirickettsiosis or Salmonid Rickettsial Septicaemia (SRS) is a bacterial disease that has a major economic impact on the Chilean salmon farming industry. Despite the fact that Piscirickettsia salmonis has been recognized as a major fish pathogen for over 20 years, the molecular strategies underlying the fish response to infection and the bacterial mechanisms of pathogenesis are poorly understood. We analysed and compared the head kidney transcriptional response of Atlantic salmon (Salmo salar) families with different levels of susceptibility to P. salmonis infection in order to reveal mechanisms that might confer infection resistance. RESULTS: We ranked forty full-sibling Atlantic salmon families according to accumulated mortality after a challenge with P. salmonis and selected the families with the lowest and highest cumulative mortalities for microarray gene expression analysis. A comparison of the response to P. salmonis infection between low and high susceptibility groups identified biological processes presumably involved in natural resistance to the pathogen. In particular, expression changes of genes linked to cellular iron depletion, as well as low iron content and bacterial load in the head kidney of fish from low susceptibility families, suggest that iron-deprivation is an innate immunity defence mechanism against P. salmonis. To complement these results, we predicted a set of iron acquisition genes from the P. salmonis genome. Identification of putative Fur boxes and expression of the genes under iron-depleted conditions revealed that most of these genes form part of the Fur regulon of P. salmonis. CONCLUSIONS: This study revealed, for the first time, differences in the transcriptional response to P. salmonis infection among Atlantic salmon families with varied levels of susceptibility to the infection. These differences correlated with changes in the abundance of transcripts encoding proteins directly and indirectly involved in the immune response; changes that highlighted the role of nutritional immunity through iron deprivation in host defence mechanisms against P. salmonis. Additionally, we found that P. salmonis has several mechanisms for iron acquisition, suggesting that this bacterium can obtain iron from different sources, including ferric iron through capturing endogenous and exogenous siderophores and ferrous iron. Our results contribute to determining the underlying resistance mechanisms of Atlantic salmon to P. salmonis infection and to identifying future treatment strategies. PMID- 26141114 TI - Cardiovascular pathologies in mucopolysaccharidosis type VII (Sly Syndrome). AB - We present the cardiac findings from the autopsy of a 28-year-old male with mucopolysaccharidosis VII (MPS VII), also known as Sly Syndrome, whose diagnosis was confirmed by biochemical testing. The patient died a sudden cardiac death. Autopsy showed thickened and stenotic aortic valve leaflets as well as marked concentric intimal thickening of the aorta and muscular arteries. There was left ventricular hypertrophy as well as mild papillary muscle thickening and fusion. Increased colloid iron staining was seen in the small- and medium-sized arteries of the heart and at the intercalated discs. We discuss the patient's premortem echocardiographic and electrocardiographic studies. In addition, we discuss the pathogenesis of MPS VII and review previous literature on its anatomic and pathologic features. PMID- 26141116 TI - Fecal Microbiota Transplant: Treatment Options for Clostridium difficile Infection in the Intensive Care Unit. AB - Clostridium difficile infection (CDI) has steadily increased in incidence since the 1990s, with an associated increase in recurrence and severity, which has in turn lead to more intensive care unit (ICU) admissions. The development of recurrent CDI, in particular, has been associated with increasing patient morbidity and mortality as well as an immense financial burden on the health care system. Recently, fecal microbiota transplantation (FMT) has received much publicity as an effective means of treatment for recurrent CDI. The goal of this review is to provide evidence-based recommendations for the diagnosis and management of CDI, with a particular focus on FMT and its utilization in the ICU. PMID- 26141115 TI - Preventing carbon nanoparticle-induced lung inflammation reduces antigen-specific sensitization and subsequent allergic reactions in a mouse model. AB - BACKGROUND: Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle induced neutrophilic lung inflammation. METHODS: Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells. RESULTS: Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific TH2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals. CONCLUSIONS: Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization. PMID- 26141117 TI - Burst Suppression for ICP Control. AB - BACKGROUND: The goal of our study was to perform a systematic review of the literature to determine the effect that burst suppression has on intracranial pressure (ICP) control. METHODS: All articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to January 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and the Grading of Recommendation Assessment Development and Education (GRADE) methodology. RESULTS: Seven articles were considered for review. A total of 108 patients were studied, all receiving burst suppression therapy. Two studies failed to document a decrease in ICP with burst suppression therapy. There were reports of severe hypotension and increased infection rates with barbiturate-based therapy. Etomidate-based suppressive therapy was linked to severe renal dysfunction. CONCLUSIONS: There currently exists both Oxford level 2b and GRADE C evidence to support that achieving burst suppression reduces ICP, and also has no effect on ICP, in severe traumatic brain injury. The literature suggests burst suppression therapy may be useful for ICP reduction in certain cases, although these situations are currently unclear. In addition, the impact on patient functional outcome is unclear. Further prospective study is warranted. PMID- 26141118 TI - Topical Review: Unique Contributions of Magnetic Resonance Imaging to Pediatric Psychology Research. AB - OBJECTIVE: This review aims to provide a brief introduction of the utility of magnetic resonance imaging (MRI) methods in pediatric psychology research, describe several exemplar studies that highlight the unique benefits of MRI techniques for pediatric psychology research, and detail methods for addressing several challenges inherent to pediatric MRI research. METHODS: Literature review. RESULTS: Numerous useful applications of MRI research in pediatric psychology have been illustrated in published research. MRI methods yield information that cannot be obtained using neuropsychological or behavioral measures. CONCLUSIONS: Using MRI in pediatric psychology research may facilitate examination of neural structures and processes that underlie health behaviors. Challenges inherent to conducting MRI research with pediatric research participants (e.g., head movement) may be addressed using evidence-based strategies. We encourage pediatric psychology researchers to consider adopting MRI techniques to answer research questions relevant to pediatric health and illness. PMID- 26141119 TI - Topical Review: Advancing Research on the Transition to Adult Care for Type 1 Diabetes. AB - OBJECTIVE: To acknowledge and address the gaps in health care transition (HCT) in type 1 diabetes (T1D) literature by proposing an expanded model that could guide future research. METHOD: Topical literature review. RESULTS: Empirical research examining the outcomes of HCT in T1D is limited by methodological and interpretive problems. The relevant evidence indicates that HCT outcomes are both multi-systemic and multidimensional; the authors propose an expanded model that incorporates multiple stakeholder perspectives of HCT outcomes. CONCLUSIONS: The development and validation of a standard index of HCT outcomes based on the expanded model of HCT outcomes could provide a means for assessing relations between HCT readiness and outcomes, facilitate the design of longitudinal studies to determine the predictive validity of HCT readiness assessment and the efficacy of HCT interventions, and inform the design and evaluation of appropriate interventions targeting those mechanisms. PMID- 26141121 TI - Highly specialized neuroradiology. PMID- 26141120 TI - The influence of early-life conditions on cardiovascular disease later in life among ethnic minority populations: a systematic review. AB - Ethnic minority groups are disproportionately affected by cardiovascular diseases (CVDs). The reasons for the high prevalence of CVD in ethnic minority groups are not fully understood. Recently, the importance of early-life developmental factors and their impact on CVDs in adulthood is increasingly being recognised, but little is known about this among ethnic minority groups. Therefore, the current paper aimed to fill this knowledge gap by reviewing the available literature to assess the influence of early-life conditions on CVDs and its risk factors in ethnic minority populations residing in Western countries. A systematic search was performed in PubMed and EMBASE between 1989 and 2014. In total, 1418 studies were identified of which 19 met the inclusion criteria. Six studies investigated the relationship between early-life anthropometrics and CVD risk factors of which all except one found significant associations between the assessed anthropometric measures and CVD risk factors. Seven studies evaluated the influence of childhood socio-economic status (SES) on CVD and risk factors of which five found significant associations between childhood SES measures and CVD risk factors. Five studies investigated the relationship between other early-life conditions including early-life nutrition, physical development, and childhood psychosocial conditions, and CVD risk factors. Four of these studies found significant associations between the assessed childhood conditions and CVD risk factors. This review reinforces the importance of early-life conditions on adult CVD in ethnic minority groups. Improvement of early-life conditions among ethnic minority groups may contribute to reducing CVD risk in these populations. PMID- 26141122 TI - Overexpression of PGC-1alpha Influences Mitochondrial Signal Transduction of Dopaminergic Neurons. AB - Parkinson's disease (PD) is a common neurodegenerative disease in the elderly. Mitochondrial dysfunction plays an important role in the pathogenesis of PD. Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is a powerful transcription factor, interacting with multiple transcription factors and widely involving in the regulation of mitochondrial biogenesis, oxidative stress, and other processes. The present study investigated the neuroprotective effects and signal transduction mechanisms of the overexpression of PGC-1alpha on N-methyl-4-phenylpyridinium ion (MPP(+))-induced mitochondrial damage in SH-SY5Y cell, establishing the cell model of overexpression of PGC 1alpha and the cell model of PD by using adenoviral vectors and MPP(+). 3-(4,5 Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) assay was used to investigate the effects of MPP(+) and adenovirus on the cell viability of SH-SY5Y cells and the cell viability of experimental groups. Western blot and real-time PCR analysis were used to detect the expression of PGC-1alpha. Flow cytometry and ELISA were used to detect mitochondrial membrane potential and the level of cytochrome C, respectively. The level of intracellular ATP and H2O2 was measured by multifunctional fluorescence microplate. Western blot analysis and real-time PCR were used to observe the expression of estrogen-related receptor alpha (ERRalpha), peroxisome proliferator-activated receptor gamma (PPARgamma), nuclear respiratory factor (NRF)-1, and NRF-2. Confocal fluorescence analysis was used to observe subcellular localization of PGC-1alpha in SH-SY5Y cells under the intervention of MPP(+). The expression of PGC-1alpha messenger RNA and protein significantly increased in Adv-PGC-1alpha + GFP groups, compared with the control and Adv-GFP groups (P < 0.01). The overexpression of PGC-1alpha could increase mitochondrial membrane potential, reduce the release of mitochondrial cytochrome C, inhibit H2O2 production, and improve the level of ATP in SH-SY5Y cells. The trend of expression of ERRalpha, PPARgamma, and NRF-1 was more consistent with PGC-1alpha, the most remarkable change is ERRalpha, but the expression of NRF-2 has no significant changes. Under the gradually increasing concentration of MPP(+), microscale PGC-1alpha gradually appeared in the cytoplasm of SH-SY5Y cells. The overexpression of PGC-1alpha can inhibit MPP(+) induced mitochondrial damage in SH-SY5Y cells, and PGC-1alpha may realize the neuroprotective effects via the ERRalpha, PPARgamma, and NRF-1 pathway. PMID- 26141124 TI - Inhibition of Protein Phosphatase 2A: Focus on the Glutamatergic System. AB - In a recent review published in Molecular Neurobiology, Kamat and colleagues (Mol Neurobiol. 2014 Dec;50(3):852-65) highlighted the cellular and molecular mechanisms involved in Okadaic acid (OKA)-induced neurotoxicity. In this review, the authors underline a wide range of pathological signaling pathways involved in OKA-induced neurotoxicity; however, the role of glutamate was only briefly described. We believe that the hyperactivation of the glutamatergic system is a key pathophysiological player in OKA-induced neurotoxicity and deserves serious attention. In this commentary, we propose an integrative model linking glutamate and PP2A and put forward some unanswered questions. PMID- 26141123 TI - Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period. AB - Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes. PMID- 26141125 TI - Malignant schwannoma of the infratemporal fossa: a case report. AB - INTRODUCTION: Malignant schwannomas or neurofibrosarcomas are rare nerve tumors of unknown etiology. These neoplasms are highly aggressive with a marked propensity for local recurrence and metastatic spread. Their management continues to be a challenge for pathologists and surgeons. Maxillofacial locations are very exceptional. We report the case of a patient with unusual malignant schwannoma of the infratemporal fossa discovered at a late evolving stage. CASE PRESENTATION: A 56-year-old woman, of Moroccan nationality, presented to our hospital in 2013 with a large right-sided hemifacial swelling that had evolved over the previous 4 months, with a limitation of mouth opening, nasal obstruction and episodes of epistaxis. A CT scan and MRI showed a large and invasive tumor occupying her right infratemporal fossa and maxillary sinus, with sphenoidal, ethmoidonasal, nasopharyngeal and intraorbital extension. A nasal endoscopic biopsy was performed. Immunohistochemical examination concluded a diagnosis of malignant schwannoma, and a palliative radiotherapy was decided; however, our patient died 10 days later. CONCLUSIONS: Malignant schwannoma of paranasal sinuses and the anterior skull base is a rare tumor that involves a high rate of local invasion. The prognosis is poorer compared to that occurring in the trunk and extremities. PMID- 26141126 TI - Temporal and spatial trends in sediment contaminants associated with toxicity in California watersheds. AB - California's Stream Pollution Trends program (SPoT) assesses long-term water quality trends, using 100 base-of-the-watershed sampling sites. Annual statewide sediment surveys from 2008 to 2012 identified consistent levels of statewide toxicity (19%), using the freshwater amphipod Hyalella azteca. Significant contaminant trends included a decrease in PCBs, stable concentrations of metals and PAHs, and a statewide increase in detections and concentrations of pyrethroid pesticides. The pyrethroid pesticide bifenthrin was detected in 69% of samples (n = 410). Detection of toxicity increased in a subset of samples tested at a more environmentally relevant test temperature (15 degrees C), and the magnitude of toxicity was much greater, indicating pyrethroid pesticides as a probable cause. Pyrethroid toxicity thresholds (LC50) were exceeded in 83% of samples with high toxicity. Principal components analysis related pyrethroids, metals and total organic carbon to urban land use. PMID- 26141127 TI - Characterisation of particulate matter on airborne pollen grains. AB - A characterization of the physical-chemical composition of the atmospheric PM adsorbed to airborne pollen was performed. Airborne pollen was sampled using a Hirst-type volumetric spore sampler and observed using a Field Emission Electron Probe Microanalyser for PM analysis. A secondary electron image was taken of each pollen grain and EDS spectra were obtained for individually adsorbed particles. All images were analysed and the size parameters of the particles adsorbed to pollen was determined. The measured particles' equivalent diameter varied between 0.1 and 25.8 MUm, mostly in the fine fraction. The dominant particulates identified were Si-rich, Organic-rich, SO-rich, Metals & Oxides and Cl-rich. Significant daily differences were observed in the physical-chemical characteristics of particles adsorbed to the airborne pollen wall. These differences were correlated with weather parameters and atmospheric PM concentration. Airborne pollen has the ability to adsorb fine particles that may enhance its allergenicity. PMID- 26141128 TI - Community-acquired Acinetobacter baumannii pneumonia. PMID- 26141129 TI - Can phosphatidylserine enhance atheroprotective activities of high-density lipoprotein? AB - Although high-density lipoprotein (HDL) is well known to be protective against atherosclerotic cardiovascular disease, therapeutic interventions to raise HDL cholesterol levels do not translate into reduction in cardiovascular risk. Due to the compositional complexity of HDL particles, molecular determinants of their atheroprotective function still remain to be clarified. Recent structural and functional data identify phospholipid as a major bioactive component of HDL. Such a role has recently been specifically evidenced for phosphatidylserine (PS); indeed, HDL content of PS displayed positive correlations with all metrics of HDL functionality assessed. This review summarizes current knowledge about HDL associated PS; possible mechanisms for its atheroprotective role are discussed and potential applications of PS to HDL-based therapies are highlighted. PMID- 26141130 TI - Origin and emergence of the sweet dessert watermelon, Citrullus lanatus. AB - BACKGROUND AND AIMS: Watermelons, Citrullus species (Cucurbitaceae), are native to Africa and have been cultivated since ancient times. The fruit flesh of wild watermelons is watery, but typically hard-textured, pale-coloured and bland or bitter. The familiar sweet dessert watermelons, C. lanatus, featuring non-bitter, tender, well-coloured flesh, have a narrow genetic base, suggesting that they originated from a series of selection events in a single ancestral population. The objective of the present investigation was to determine where dessert watermelons originated and the time frame during which sweet dessert watermelons emerged. KEY FINDINGS: Archaeological remains of watermelons, mostly seeds, that date from 5000 years ago have been found in northeastern Africa. An image of a large, striped, oblong fruit on a tray has been found in an Egyptian tomb that dates to at least 4000 years ago. The Greek word pepon, Latin pepo and Hebrew avattiah of the first centuries CE were used for the same large, thick-rinded, wet fruit which, evidently, was the watermelon. Hebrew literature from the end of the second century CE and Latin literature from the beginning of the sixth century CE present watermelons together with three sweet fruits: figs, table grapes and pomegranates. Wild and primitive watermelons have been observed repeatedly in Sudan and neighbouring countries of northeastern Africa. CONCLUSIONS: The diverse evidence, combined, indicates that northeastern Africa is the centre of origin of the dessert watermelon, that watermelons were domesticated for water and food there over 4000 years ago, and that sweet dessert watermelons emerged in Mediterranean lands by approximately 2000 years ago. Next generation ancient-DNA sequencing and state-of-the-art genomic analysis offer opportunities to rigorously assess the relationships among ancient and living wild and primitive watermelons from northeastern Africa, modern sweet dessert watermelons and other Citrullus taxa. PMID- 26141132 TI - Phylogenetic reconstruction using four low-copy nuclear loci strongly supports a polyphyletic origin of the genus Sorghum. AB - BACKGROUND AND AIMS: Sorghum is an essential grain crop whose evolutionary placement within the Andropogoneae has been the subject of scrutiny for decades. Early studies using cytogenetic and morphological data point to a poly- or paraphyletic origin of the genus; however, acceptance of poly- or paraphyly has been met with resistance. This study aimed to address the species relationships within Sorghum, in addition to the placement of Sorghum within the tribe, using a phylogenetic approach and employing broad taxon sampling. METHODS: From 16 diverse Sorghum species, eight low-copy nuclear loci were sequenced that are known to play a role in morphological diversity and have been previously used to study evolutionary relationships in grasses. Further, the data for four of these loci were combined with those from 57 members of the Andropogoneae in order to determine the placement of Sorghum within the tribe. Both maximum likelihood and Bayesian analyses were performed on multilocus concatenated data matrices. KEY RESULTS: The Sorghum-specific topology provides strong support for two major lineages, in alignment with earlier studies employing chloroplast and internal transcribed spacer (ITS) markers. Clade I is composed of the Eu-, Chaeto- and Heterosorghum, while clade II contains the Stipo- and Parasorghum. When combined with data from the Andropogoneae, Clade II resolves as sister to a clade containing Miscanthus and Saccharum with high posterior probability and bootstrap support, and to the exclusion of Clade I. CONCLUSIONS: The results provide compelling evidence for a two-lineage polyphyletic ancestry of Sorghum within the larger Andropogoneae, i.e. the derivation of the two major Sorghum clades from a unique common ancestor. Rejection of monophyly in previous molecular studies is probably due to limited taxon sampling outside of the genus. The clade consisting of Para- and Stiposorghum resolves as sister to Miscanthus and Saccharum with strong node support. PMID- 26141131 TI - Site-directed mutagenesis substituting cysteine for serine in 2-Cys peroxiredoxin (2-Cys Prx A) of Arabidopsis thaliana effectively improves its peroxidase and chaperone functions. AB - BACKGROUND AND AIMS: The 2-Cys peroxiredoxin (Prx) A protein of Arabidopsis thaliana performs the dual functions of a peroxidase and a molecular chaperone depending on its conformation and the metabolic conditions. However, the precise mechanism responsible for the functional switching of 2-Cys Prx A is poorly known. This study examines various serine-to-cysteine substitutions on alpha helix regions of 2-Cys Prx A in Arabidopsis mutants and the effects they have on the dual function of the protein. METHODS: Various mutants of 2-Cys Prx A were generated by replacing serine (Ser) with cysteine (Cys) at different locations by site-directed mutagenesis. The mutants were then over-expressed in Escherichia coli. The purified protein was further analysed by size exclusion chromatography, polyacrylamide gel electrophoresis, circular dichroism spectroscopy and transmission electron microscopy (TEM) and image analysis. Peroxidase activity, molecular chaperone activity and hydrophobicity of the proteins were also determined. Molecular modelling analysis was performed in order to demonstrate the relationship between mutation positions and switching of 2-Cys Prx A activity. KEY RESULTS: Replacement of Ser(150) with Cys(150) led to a marked increase in holdase chaperone and peroxidase activities of 2-Cys Prx A, which was associated with a change in the structure of an important domain of the protein. Molecular modelling demonstrated the relationship between mutation positions and the switching of 2-Cys Prx A activity. Examination of the alpha2 helix, dimer dimer interface and C-term loop indicated that the peroxidase function is associated with a fully folded alpha2 helix and easy formation of a stable reduced decamer, while a more flexible C-term loop makes the chaperone function less likely. CONCLUSIONS: Substitution of Cys for Ser at amino acid location 150 of the alpha-helix of 2-Cys Prx A regulates/enhances the dual enzymatic functions of the 2-Cys Prx A protein. If confirmed in planta, this leads to the potential for it to be used to maximize the functional utility of 2-Cys Prx A protein for improved metabolic functions and stress resistance in plants. PMID- 26141134 TI - UK lags behind other countries on cancer survival but outperforms on low antibiotic prescribing, report finds. PMID- 26141133 TI - Long-term outcomes of intensity-modulated radiation therapy combined with neoadjuvant androgen deprivation therapy under an early salvage policy for patients with T3-T4N0M0 prostate cancer. AB - BACKGROUND: Long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) combined with neoadjuvant (NA) androgen deprivation therapy (ADT) under an early salvage policy in patients with locally advanced prostate cancer (LAPC) were evaluated. METHODS: Data from 120 patients with T3-T4N0M0 adenocarcinoma of the prostate treated with IMRT were analyzed. NA-ADT with a median duration of 6 months was provided in all cases. Seventy-eight Gy, at 2 Gy per fraction, was delivered to the prostate and seminal vesicles. Adjuvant ADT (A ADT) was not provided for any patient following the completion of IMRT. Salvage ADT (S-ADT) commenced when PSA values >4 ng/ml. RESULTS: The median follow-up period was 97 months. S-ADT was initiated in 39 patients. The median PSA value at the initiation of S-ADT was 5.7 ng/ml. The 8-year biochemical relapse-free survival, prostate cancer-specific survival, overall survival and S-ADT-free rates were 53.2 % [95 % confidence interval (CI) 43.4, 62.1], 96.6 % (95 % CI 91.2, 98.7), 89.1 % (95 % CI 81.5, 93.7) and 66.6 % (95 % CI 60, 74.6), respectively. The estimated 8-year cumulative incidence rates of grade 2-3 late gastrointestinal, and grade 2-3 genitourinary toxicity were 7.6 and 10.7 %, respectively. No grade 4 toxicity was observed. CONCLUSIONS: High-dose IMRT, combined with NA-ADT for LAPC, was associated with favorable long-term disease specific and overall survival outcomes, despite non-provision of A-ADT under the early S-ADT provision policy. This approach may represent a viable alternative to uniform provision of long-term A-ADT, because two-thirds of the patients maintained ADT-free status over an 8-year period after IMRT. Prospective trials will be required. PMID- 26141135 TI - Rate of aspiration pneumonia in hospitalized Parkinson's disease patients: a cross-sectional study. AB - BACKGROUND: Aspiration pneumonia is an important cause of morbidity and mortality in Parkinson's disease (PD). Clinical characteristics of PD patients in addition to specific alterations in swallowing mechanisms contribute to higher swallowing times and impairment in the effective clearance of the airway. These issues may render patients more prone to dysphagia and aspiration events. We aimed to determine the frequency of aspiration events in a hospitalized PD cohort, and to report the number of in-hospital swallow evaluations. METHODS: A retrospective single center chart review of 212 PD patients who had 339 hospital encounters was performed from January 2011 to March 2013. Demographics, clinical characteristics, and reasons for encounters were documented. The number of in hospital aspiration events and the number of swallowing evaluations and also the implementation of aspiration precautions were recorded. RESULTS: The cohort had a mean age of 74.1 (SD = 10.1) years with mean disease duration of 6 (SD = 6.3) years. Fifty-two hospital encounters (15.3%) were related to a pulmonary cause. In-hospital aspiration pneumonia events were reported in 8 (2.4%) of the total encounters. Swallow evaluations were performed in 25% of all cases, and aspiration precautions were initiated in 32% of the encounters. The data revealed that 1/8 patient had swallowing evaluations performed prior to an aspiration event. CONCLUSIONS: In-hospital aspiration pneumonia events were reported in 2.4% of the hospitalized PD cohort. Preventive measures and precautions were not routinely performed, however rates of aspiration were relatively low. The results highlight the need for more research into screening and monitoring of swallowing problems in PD patients during hospital encounters. PMID- 26141136 TI - Osteoligamentous injuries of the medial ankle joint. AB - Injuries of the ankle joint have a high incidence in daily life and sports, thus, playing an important socioeconomic role. Therefore, proper diagnosis and adequate treatment are mandatory. While most of the ligament injuries around the ankle joint are treated conservatively, great controversy exists on how to treat deltoid ligament injuries in ankle fractures. Missed injuries and inadequate treatment of the medial ankle lead to inferior outcome with instability, progressive deformity, and ankle joint osteoarthritis. PMID- 26141137 TI - The most important tasks for peer reviewers evaluating a randomized controlled trial are not congruent with the tasks most often requested by journal editors. AB - BACKGROUND: The peer review process is a cornerstone of biomedical research publications. However, it may fail to allow the publication of high-quality articles. We aimed to identify and sort, according to their importance, all tasks that are expected from peer reviewers when evaluating a manuscript reporting the results of a randomized controlled trial (RCT) and to determine which of these tasks are clearly requested by editors in their recommendations to peer reviewers. METHODS: We identified the tasks expected of peer reviewers from 1) a systematic review of the published literature and 2) recommendations to peer reviewers for 171 journals (i.e., 10 journals with the highest impact factor for 14 different medical areas and all journals indexed in PubMed that published more than 15 RCTs over 3 months regardless of the medical area). Participants who had peer-reviewed at least one report of an RCT had to classify the importance of each task relative to other tasks using a Q-sort technique. Finally, we evaluated editors' recommendations to authors to determine which tasks were clearly requested by editors in their recommendations to peer reviewers. RESULTS: The Q sort survey was completed by 203 participants, 93 (46 %) with clinical expertise, 72 (36 %) with methodological/statistical expertise, 17 (8 %) with expertise in both areas, and 21 (10 %) with other expertise. The task rated most important by participants (evaluating the risk of bias) was clearly requested by only 5 % of editors. In contrast, the task most frequently requested by editors (provide recommendations for publication), was rated in the first tertile only by 21 % of all participants. CONCLUSIONS: The most important tasks for peer reviewers were not congruent with the tasks most often requested by journal editors in their guidelines to reviewers. PMID- 26141138 TI - 'True Blood' The Critical Care Story: An audit of blood sampling practice across three adult, paediatric and neonatal intensive care settings. AB - BACKGROUND: Anaemia is common in critically ill patients, and has a significant negative impact on patients' recovery. Blood conservation strategies have been developed to reduce the incidence of iatrogenic anaemic caused by sampling for diagnostic testing. OBJECTIVES: Describe practice and local guidelines in adult, paediatric and neonatal Australian intensive care units (ICUs) regarding blood sampling and conservation strategies. METHODS: Cross-sectional descriptive study, conducted July 2013 over one week in single adult, paediatric and neonatal ICUs in Brisbane. Data were collected on diagnostic blood samples obtained during the study period, including demographic and acuity data of patients. Institutional blood conservation practice and guidelines were compared against seven evidence based recommendations. RESULTS: A total of 940 blood sampling episodes from 96 patients were examined across three sites. Arterial blood gas was the predominant reason for blood sampling in each unit, accounting for 82% of adult, 80% of paediatric and 47% of neonatal samples taken (p<0.001). Adult patients had significantly more median [IQR] samples per day in comparison to paediatrics and neonates (adults 5.0 [2.4]; paediatrics 2.3 [2.9]; neonatal 0.7 [2.7]), which significantly increased median [IQR] blood sampling costs per day (adults AUD$101.11 [54.71]; paediatrics AUD$41.55 [56.74]; neonatal AUD$8.13 [14.95]; p<0.001). The total volume of samples per day (median [IQR]) was also highest in adults (adults 22.3mL [16.8]; paediatrics 5.0mL [1.0]; neonates 0.16mL [0.4]). There was little information about blood conservation strategies in the local clinical practice guidelines, with the adult and neonatal sites including none of the seven recommendations. CONCLUSIONS: There was significant variation in blood sampling practice and conservation strategies between critical care settings. This has implications not only for anaemia but also infection control and healthcare costs. PMID- 26141140 TI - Extended Ureteral Stricture Corrected With Appendiceal Replacement in a Kidney Transplant Recipient. AB - OBJECTIVE: To present our technique of ureteral replacement with an appendicovesicostomy for the treatment of extended ureteral stricture after kidney transplantation. Ureteral stricture represents a urologic complication that may cause progressive function impairment and graft loss. Symptomatic ureteral stenosis is generally treated with a percutaneous nephrostomy and ureteral stenting. This approach may be initially effective, but often does not offer a long-term solution. METHODS: A 48-year-old Caucasian man underwent kidney transplantation from a heart-beating deceased donor. The graft was transplanted to the right iliac fossa. Ureterovesical anastomosis was performed following the Lich-Gregoir technique. The postoperative period and follow-up were uneventful. Six months later the patient experienced an episode of acute pyelonephritis with hydronephrosis. A percutaneous nephrostomy was inserted, and an anterograde pyelography confirmed proximal dilatation with severe distal stenosis involving the entire ureter including the ureterovesical anastomosis. A 9 French Double-J stent was inserted antegradely and the patient was prepared for surgery. RESULTS: We decided therefore to use the appendix as a conduit between the proximal transplant ureter and the bladder It was interposed with an isoperistaltic orientation and anastomosed to the ureter proximally and to the bladder distally (Lich-Gregoir reimplantation) using interrupted absorbable 5/0 sutures over a 10 Fr Double-J stent. The urethral catheter was removed on day 9 postoperatively and the patient was discharged with normal parameters. At 1 year follow-up the patient remains well. CONCLUSION: The positive outcome confirms how the use of appendix as ureteral replacement is feasible and effective, allowing the salvage of the renal allograft. PMID- 26141139 TI - Long-term Artificial Urinary Sphincter Outcomes Following a Prior Rectourethral Fistula Repair. AB - OBJECTIVE: To determine the long-term outcomes of artificial urinary sphincter (AUS) implantation following a successful rectourethral fistula (RUF) repair. MATERIALS AND METHODS: Between January 1, 2006 and January 1, 2012, a total of 26 patients underwent successful repair of an RUF. Stress urinary incontinence was treated in 6 patients (23%) with implantation of an AUS. Preoperative and postoperative evaluation included demographic variables, voiding diaries, 24-hour pad weight, urodynamic characteristics, operative time, estimated blood loss, complication rates, follow-up time, and cuff selection. RESULTS: All 6 patients underwent successful RUF repair using a perineal approach. Mean age was 64.3 years (range 58-74). Mean follow-up after repair was 51.5 months (range 34-64). RUF etiology included radical prostatectomy (4), brachytherapy + external beam radiotherapy (1), and cryotherapy + external beam radiotherapy (1). The median time between RUF repair and AUS placement was 12 months (range 2-41). No intraoperative complications occurred during AUS implantation. The average operative time was 61.8 minutes with an estimated blood loss of 24 mL. The initial cuff size selected was 4.0 or 4.5 cm, and no patient required transcorporal cuff placement. Pad use was reported as <=1 pad per day in all 6 patients at the initial 3-month follow-up. Median follow-up after AUS placement was 43.5 months (5-55). No patient required revision or removal for mechanical complications, infection, or erosion. No patient had recurrence of their previously repaired RUF or new-onset fecal incontinence. CONCLUSION: Patients who require placement of an AUS after an RUF repair seem to fare just as well as patients who undergo primary AUS implantation with no increased rate of complications postoperatively. PMID- 26141141 TI - Pharmacokinetics of the transdermal delivery of benfotiamine. AB - AIMS: Accumulation of advanced glycation endpoints is a trigger to the development of diabetic peripheral neuropathy, which is a common complication of diabetes. Oral administration of benfotiamine (BFT) has shown some preclinical and clinical promise as a treatment for diabetic peripheral neuropathy. The purpose of this study was to evaluate the method of transdermal delivery of BFT as a possible, viable route of administration for the treatment of diabetic peripheral neuropathy. METHODS: A single application of 10 mg of BFT was given to guinea pigs topically. The levels of thiamine (T), thiamine monophosphate, thiamine diphosphate, S-benzoylthiamine and BFT were measured in the blood, skin and muscle at different time points within 24 h. RESULTS: At the 24-h time point, following the single BFT dose, the T level was increased 10* in the blood, more than 7* in the skin and almost 4* in the muscle compared to the untreated animals. The total T content (total) was increased 7* in the blood, 17* in the skin and 3* in the muscle compared to the untreated animals. CONCLUSIONS: This strong increase in the tissue levels of T and the associated metabolic derivatives levels found in the blood and local tissues following a single dose indicate that topically applied BFT may be a viable and advantageous delivery method for the treatment of diabetic peripheral neuropathy. PMID- 26141142 TI - The risks and benefits of switching patients with schizophrenia or schizoaffective disorder from two to one antipsychotic medication: a randomized controlled trial. AB - BACKGROUND: Despite little evidence to support its use and practice guidelines discouraging the practice, antipsychotic polypharmacy is widely prevalent in schizophrenia. This randomized controlled trial studied the effects of switching patients stable on two antipsychotic medications to one antipsychotic medication. METHOD: 104 adult outpatients with schizophrenia from 7 community mental health centers clinically stable on concurrent treatment with 2 antipsychotics were randomly assigned to stay on polypharmacy or to switch to antipsychotic monotherapy. Participants were followed for 1-year with assessments of symptoms and side effects occurring every 60days (7 total assessments). We examined differences in time trajectories in symptoms (PANSS, CGI) and side effects (EPS, metabolic, other) as a function of group assignment (switch vs. stay) and time, using intention-to-treat analysis. RESULTS: Participants who switched to antipsychotic monotherapy experienced greater increases in symptoms than stay patients. These differences emerged in the second 6months of the trial. All-cause discontinuation rates over the 1-year trial were higher in the switch-to monotherapy group than in the stay-on-polypharmacy group (42% vs. 13%; p<0.01). There were no differences in change over time in any of the side effect measures, except that stay patients experienced a greater decrease in Simpson Angus total scores than switch patients. CONCLUSION: Clinicians should be cautious in switching patients with chronic schizophrenia who are stable on 2 antipsychotics to one antipsychotic. Given the challenges in discontinuing antipsychotic polypharmacy, adequate trials of evidence-based treatments such as clozapine and long-acting injectable antipsychotics should be undertaken in inadequately responsive schizophrenia patients before moving to antipsychotic polypharmacy. PMID- 26141143 TI - Ascitic fluid TREM-1 for the diagnosis of spontaneous bacterial peritonitis. PMID- 26141144 TI - Gastroenterology training in Europe-unmet educational needs beyond the machines: response from the European Section and Board of Gastroenterology. PMID- 26141146 TI - Possible hormonal interaction for eliciting courtship behavior in the male newt, Cynops pyrrhogaster. AB - Reproductive behavior in amphibians, as in other vertebrate animals, is under the control of multiple hormonal substances. Prolactin (PRL), arginine vasotocin (AVT), androgen, and 7alpha-hydroxypregnenolone (7alpha-OH PREG), four such substances with hormonal activity, are known to be involved in the expression of the tail vibration behavior which is the initial step of courtship performed by the male newt, Cynops pyrrhogaster. As current information on the interaction(s) between these hormones in terms of eliciting tail vibration behavior is limited, we have investigated whether the decline of expression of tail vibration behavior due to suppression of the activity of any one of these hormones can be restored by supplying any one of the other three hormones exogenously. Expression of the behavior was determined in terms of incidence (% of test animals exhibiting the behavior) and frequency (number of times that the behavior was repeated during the test period). Neither PRL nor androgen restored the decline in the incidence and frequency of the tail vibration behavior caused by the suppression of the activity of any one of other three hormones. AVT completely restored both the anti-PRL antibody-induced and flutamide (an androgen receptor antagonist) induced, but not ketoconazole (an inhibitor of the steroidogenic CYP enzymes) induced decline in the incidence and frequency of the tail vibration behavior. The neurosteroid, 7alpha-OH PREG, failed to restore flutamide-induced decline in the incidence and frequency of the behavior. However, it was able to restore both anti-PRL antibody-induced and AVT receptor antagonist-induced decline in the incidence, but not in the frequency of the behavior. In another experiment designed to see the activity of hormones enhancing the frequency of the tail vibration behavior, AVT was revealed to be more potent than 7alpha-OH PREG. The role of each hormonal substance in determining the expression of the tail vibration behavior was discussed based on the results. PMID- 26141145 TI - Determinants and significance of corticosterone regulation in the songbird brain. AB - Songbirds exhibit significant adult neuroplasticity that, together with other neural specializations, makes them an important model system for neurobiological studies. A large body of work also points to the songbird brain as a significant target of steroid hormones, including corticosterone (CORT), the primary avian glucocorticoid. Whereas CORT positively signals the brain for many functions, excess CORT may interfere with natural neuroplasticity. Consequently, mechanisms may exist to locally regulate CORT levels in brain to ensure optimal concentrations. However, most studies in songbirds measure plasma CORT as a proxy for levels at target tissues. In this paper, we review literature concerning circulating CORT and its effects on behavior in songbirds, and discuss recent work suggesting that brain CORT levels are regulated independently of changes in adrenal secretion. We review possible mechanisms for CORT regulation in the avian brain, including corticosteroid-binding globulins, p-glycoprotein activity in the blood-brain barrier and CORT metabolism by the 11beta hydroxysteroid dehydrogenases. Data supporting a role for CORT regulation within the songbird brain have only recently begun to emerge, suggesting that this is an avenue for important future research. PMID- 26141147 TI - Non-invasive monitoring of adrenocortical activity in captive African Penguin (Spheniscus demersus) by measuring faecal glucocorticoid metabolites. AB - Measurement of faecal glucocorticoid metabolites (FGMs) has become a useful and widely-accepted method for the non-invasive evaluation of stress in vertebrates. In this study we assessed the adrenocortical activity of five captive African Penguins (Spheniscus demersus) by means of FGM evaluation following a biological stressor, i.e. capture and immobilization. In addition, we detected individual differences in secretion of FGMs during a stage of the normal biological cycle of penguins, namely the breeding period, without any external or induced causes of stress. Our results showed that FGM concentrations peaked 5.5-8h after the induced stress in all birds, and significantly decreased within 30 h. As predictable, the highest peak of FGMs (6591 ng/g) was reached by the youngest penguin, which was at its first experience with the stressor. This peak was 1.8 2.7-fold higher compared to those of the other animals habituated to the stimulus. For the breeding period, our results revealed that the increase in FGMs compared to ordinary levels, and the peaks of FGMs, varied widely depending on the age and mainly on the reproductive state of the animal. The bird which showed the lowest peak (2518 ng/g) was an old male that was not in a reproductive state at the time of the study. Higher FGM increases and peaks were reached by the two birds which were brooding (male: 5552%, 96,631 ng/g; female: 1438%, 22,846 ng/g) and by the youngest bird (1582%, 39,700 ng/g). The impact of the reproductive state on FGM levels was unexpected compared to that produced by the induced stress. The EIA used in this study to measure FGM levels proved to be a reliable tool for assessing individual and biologically-relevant changes in FGM concentrations in African Penguin. Moreover, this method allowed detection of physiological stress during the breeding period, and identification of individual differences in relation to the reproductive status. The increase in FGM levels as a response to capture and immobilization suggests that the measured metabolites are appropriate indicators of adrenal activity in these birds. PMID- 26141148 TI - The secretogranin-II derived peptide secretoneurin modulates electric behavior in the weakly pulse type electric fish, Brachyhypopomus gauderio. AB - Secretoneurin (SN) in the preoptic area and pituitary of mammals and fish has a conserved close association with the vasopressin and oxytocin systems, members of a peptide family that are key in the modulation of sexual and social behaviors. Here we show the presence of SN-immunoreactive cells and projections in the brain of the electric fish, Brachyhypopomus gauderio. Secretoneurin colocalized with vasotocin (AVT) and isotocin in cells and fibers of the preoptic area. In the rostral pars distalis of the pituitary, many cells were both SN and prolactin positive. In the hindbrain, at the level of the command nucleus of the electric behavior (pacemaker nucleus; PN), some of SN-positive fibers colocalized with AVT. We also explored the potential neuromodulatory role of SN on electric behavior, specifically on the rate of the electric organ discharge (EOD) that signals arousal, dominance and subordinate status. Each EOD is triggered by the command discharge of the PN, ultimately responsible for the basal EOD rate. SN modulated diurnal basal EOD rate in freely swimming fish in a context-dependent manner; determined by the initial value of EOD rate. In brainstem slices, SN partially mimicked the in vivo behavioral effects acting on PN firing rate. Taken together, our results suggest that SN may regulate electric behavior, and that its effect on EOD rate may be explained by direct action of SN at the PN level through either neuroendocrine and/or endocrine mechanisms. PMID- 26141150 TI - Metabolic engineering of Escherichia coli using CRISPR-Cas9 meditated genome editing. AB - Engineering cellular metabolism for improved production of valuable chemicals requires extensive modulation of bacterial genome to explore complex genetic spaces. Here, we report the development of a CRISPR-Cas9 based method for iterative genome editing and metabolic engineering of Escherichia coli. This system enables us to introduce various types of genomic modifications with near 100% editing efficiency and to introduce three mutations simultaneously. We also found that cells with intact mismatch repair system had reduced chance to escape CRISPR mediated cleavage and yielded increased editing efficiency. To demonstrate its potential, we used our method to integrate the beta-carotene synthetic pathway into the genome and to optimize the methylerythritol-phosphate (MEP) pathway and central metabolic pathways for beta-carotene overproduction. We collectively tested 33 genomic modifications and constructed more than 100 genetic variants for combinatorially exploring the metabolic landscape. Our best producer contained15 targeted mutations and produced 2.0 g/L beta-carotene in fed batch fermentation. PMID- 26141149 TI - Precise metabolic engineering of carotenoid biosynthesis in Escherichia coli towards a low-cost biosensor. AB - Micronutrient deficiencies, including zinc deficiency, are responsible for hundreds of thousands of deaths annually. A key obstacle to allocating scarce treatment resources is the ability to measure population blood micronutrient status inexpensively and quickly enough to identify those who most need treatment. This paper develops a metabolically engineered strain of Escherichia coli to produce different colored pigments (violacein, lycopene, and beta carotene) in response to different extracellular zinc levels, for eventual use in an inexpensive blood zinc diagnostic test. However, obtaining discrete color states in the carotenoid pathway required precise engineering of metabolism to prevent reaction at low zinc concentrations but allow complete reaction at higher concentrations, and all under the constraints of natural regulator limitations. Hence, the metabolic engineering challenge was not to improve titer, but to enable precise control of pathway state. A combination of gene dosage, post transcriptional, and post-translational regulation was necessary to allow visible color change over physiologically relevant ranges representing a small fraction of the regulator's dynamic response range, with further tuning possible by modulation of precursor availability. As metabolic engineering expands its applications and develops more complex systems, tight control of system components will likely become increasingly necessary, and the approach presented here can be generalized to other natural sensing systems for precise control of pathway state. PMID- 26141151 TI - No association of p53 codon 72 polymorphism with idiopathic recurrent pregnancy loss in Korean population. AB - OBJECTIVE: The balance of apoptosis and proliferation is an important part in the embryonic development during pregnancy. It has been reported that the p53 gene plays a significant role in angiogenesis and placental development, namely in reproduction and is suggested as a potential mediator of pregnancy. This study was performed to investigate whether the genetic polymorphism of the p53 gene is associated with idiopathic recurrent pregnancy loss (RPL). STUDY DESIGN: We conducted a case-control study in the Korean population. Study subjects consisted of 294 patients with idiopathic RPL and 300 postmenopausal controls. The genotyping for the p53 codon 72 polymorphism was performed using a Taqman assay. Continuous variables were compared using Student's t test and the chi(2) test was used to evaluate differences in the genotype distributions between the RPL and the controls. RESULTS: There were no significant differences in the genotype distributions or allele frequencies of the p53 codon 72 polymorphism between the RPL and control group. There was also no significant association between the p53 codon 72 polymorphism and RPL risk in both recessive (Pro/Pro vs. Arg-carriers, p=0.314) and dominant model (Pro-carriers vs. Arg/Arg, p=0.383: data not shown). CONCLUSION: The codon 72 polymorphism in the p53 gene did not show any correlation with idiopathic RPL in Korean women, implying that it may not be susceptible allelic variants or be insufficient to cause RPL. PMID- 26141152 TI - Biomechanical properties and microstructure of human ventricular myocardium. AB - In the multidisciplinary field of heart research it is of utmost importance to identify accurate myocardium material properties for the description of phenomena such as mechano-electric feedback or heart wall thickening. A rationally-based material model is required to understand the highly nonlinear mechanics of complex structures such as the passive myocardium under different loading conditions. Unfortunately, to date there are no experimental data of human heart tissues available to estimate material parameters and to develop adequate material models. This study aimed to determine biaxial extension and triaxial shear properties and the underlying microstructure of the passive human ventricular myocardium. Using new state-of-the-art equipment, planar biaxial extension tests were performed to determine the biaxial extension properties of the passive ventricular human myocardium. Shear properties of the myocardium were examined by triaxial simple shear tests performed on small cubic specimens excised from an adjacent region of the biaxial extension specimens. The three dimensional microstructure was investigated through second-harmonic generation (SHG) microscopy on optically cleared tissues, which emphasized the 3D orientation and dispersion of the myofibers and adjacent collagen fabrics. The results suggest that the passive human LV myocardium under quasi-static and dynamic multiaxial loadings is a nonlinear, anisotropic (orthotropic), viscoelastic and history-dependent soft biological material undergoing large deformations. Material properties of the tissue components along local microstructural axes drive the nonlinear and orthotropic features of the myocardium. SHG microscopy investigation revealed detailed information about the myocardial microstructure due to its high resolution. It enabled the identification of structural parameters such as the fiber and the sheet orientations and corresponding dispersions. With this complete set of material data, a sophisticated material model and associated material parameters can be defined for a better description of the biomechanical response of the ventricular myocardium in humans. Such a model will lead to more accurate computational simulations to better understand the fundamental underlying ventricular mechanics, a step needed in the improvement of medical treatment of heart diseases. STATEMENT OF SIGNIFICANCE: Unfortunately, to date there are no experimental data of human heart tissues available for material parameter estimation and the development of adequate material models. In this manuscript novel biaxial tensile and shear test data at different specimen orientations are presented, which allowed to adequately capture the direction-dependent material response. With these complete sets of mechanical data, combined with their underlying microstructural data (also presented herein), sophisticated material models and associated material parameters can be defined for the description of the mechanical behavior of the ventricular myocardium in humans. Such models will lead to accurate computational simulations to better understand the fundamental underlying ventricular mechanics, a step needed in the improvement of medical treatment of heart diseases. PMID- 26141153 TI - A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain. AB - The generation of functional biomimetic skeletal muscle constructs is still one of the fundamental challenges in skeletal muscle tissue engineering. With the notion that structure strongly dictates functional capabilities, a myriad of cell types, scaffold materials and stimulation strategies have been combined. To further optimize muscle engineered constructs, we have developed a novel bioreactor system (MagneTissue) for rapid engineering of skeletal muscle-like constructs with the aim to resemble native muscle in terms of structure, gene expression profile and maturity. Myoblasts embedded in fibrin, a natural hydrogel that serves as extracellular matrix, are subjected to mechanical stimulation via magnetic force transmission. We identify static mechanical strain as a trigger for cellular alignment concomitant with the orientation of the scaffold into highly organized fibrin fibrils. This ultimately yields myotubes with a more mature phenotype in terms of sarcomeric patterning, diameter and length. On the molecular level, a faster progression of the myogenic gene expression program is evident as myogenic determination markers MyoD and Myogenin as well as the Ca(2+) dependent contractile structural marker TnnT1 are significantly upregulated when strain is applied. The major advantage of the MagneTissue bioreactor system is that the generated tension is not exclusively relying on the strain generated by the cells themselves in response to scaffold anchoring but its ability to subject the constructs to individually adjustable strain protocols. In future work, this will allow applying mechanical stimulation with different strain regimes in the maturation process of tissue engineered constructs and elucidating the role of mechanotransduction in myogenesis. STATEMENT OF SIGNIFICANCE: Mechanical stimulation of tissue engineered skeletal muscle constructs is a promising approach to increase tissue functionality. We have developed a novel bioreactor based 3D culture system, giving the user the possibility to apply different strain regimes like static, cyclic or ramp strain to myogenic precursor cells embedded in a fibrin scaffold. Application of static mechanical strain leads to alignment of fibrin fibrils along the axis of strain and concomitantly to highly aligned myotube formation. Additionally, the pattern of myogenic gene expression follows the temporal progression observed in vivo with a more thorough induction of the myogenic program when static strain is applied. Ultimately, the strain protocol used in this study results in a higher degree of muscle maturity demonstrated by enhanced sarcomeric patterning and increased myotube diameter and length. The introduced bioreactor system enables new possibilities in muscle tissue engineering as longer cultivation periods and different strain applications will yield tissue engineered muscle-like constructs with improved characteristics in regard to functionality and biomimicry. PMID- 26141154 TI - Horizontal gene transfer in an acid mine drainage microbial community. AB - BACKGROUND: Horizontal gene transfer (HGT) has been widely identified in complete prokaryotic genomes. However, the roles of HGT among members of a microbial community and in evolution remain largely unknown. With the emergence of metagenomics, it is nontrivial to investigate such horizontal flow of genetic materials among members in a microbial community from the natural environment. Because of the lack of suitable methods for metagenomics gene transfer detection, microorganisms from a low-complexity community acid mine drainage (AMD) with near complete genomes were used to detect possible gene transfer events and suggest the biological significance. RESULTS: Using the annotation of coding regions by the current tools, a phylogenetic approach, and an approximately unbiased test, we found that HGTs in AMD organisms are not rare, and we predicted 119 putative transferred genes. Among them, 14 HGT events were determined to be transfer events among the AMD members. Further analysis of the 14 transferred genes revealed that the HGT events affected the functional evolution of archaea or bacteria in AMD, and it probably shaped the community structure, such as the dominance of G-plasma in archaea in AMD through HGT. CONCLUSIONS: Our study provides a novel insight into HGT events among microorganisms in natural communities. The interconnectedness between HGT and community evolution is essential to understand microbial community formation and development. PMID- 26141155 TI - Reaching the hard to reach: longitudinal investigation of adolescents' attendance at an after-school sexual and reproductive health programme in Western Cape, South Africa. AB - BACKGROUND: Adolescents need access to effective sexual and reproductive health (SRH) interventions, but face barriers accessing them through traditional health systems. School-based approaches might provide accessible, complementary strategies. We investigated whether a 21-session after-school SRH education programme and school health service attracted adolescents most at risk for adverse SRH outcomes and explored motivators for and barriers to attendance. METHODS: Grade 8 adolescents (average age 13 years) from 20 schools in the intervention arm of an HIV prevention cluster randomised controlled trial in the Western Cape Province of South Africa, were invited to participate in an after school SRH program and to attend school health services. Using a longitudinal design, we surveyed participants at baseline, measured their attendance at weekly after-school sessions for 6 months and surveyed them post-intervention. We examined factors associated with attendance using bivariate and multiple logistic and Poisson regression analyses, and through thematic analysis of qualitative data. RESULTS: The intervention was fully implemented in 18 schools with 1576 trial participants. The mean attendance of the 21-session SRH programme was 8.8 sessions (S.D. 7.5) among girls and 6.9 (S.D. 7.2) among boys. School health services were visited by 17.3 % (14.9 % of boys and 18.7 % of girls). Adolescents who had their sexual debut before baseline had a lower rate of session attendance compared with those who had not (6.3 vs 8.5, p < .001). Those who had been victims of sexual violence or intimate partner violence (IPV), and who had perpetrated IPV also had lower rates of attendance. Participants were motivated by a wish to receive new knowledge, life coaching and positive attitudes towards the intervention. The unavailability of safe transport and domestic responsibilities were the most common barriers to attendance. Only two participants cited negative attitudes about the intervention as the reason they did not attend. CONCLUSIONS: Reducing structural barriers to attendance, after school interventions are likely to reach adolescents with proven-effective SRH interventions. However, special attention is required to reach vulnerable adolescents, through offering different delivery modalities, improving the school climate, and providing support for adolescents with mental health problems and neurodevelopmental academic problems. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56270821 ; Registered 13 February 2013. PMID- 26141156 TI - The Colored, Eco-Genetic Relationship Map (CEGRM): A Conceptual Approach and Tool for Genetic Counseling Research. AB - The Colored Ecological and Genetic Relational Map (CEGRM) [pronounced see-gram] is a conceptual approach and tool for presenting information about family and nonkin relationships and stories about inherited diseases in a simple, understandable form. It combines information that can be derived from pedigrees, genograms, ecomaps, and social network analysis in a single, or series of, pictorial maps based on colors and shapes. The CEGRM is based on a social systems perspective, particularly emphasizing social exchange and resource theories. The CEGRM should be particularly useful in genetic counseling research with members of suspected cancer-risk families or families with other late-onset inherited diseases. A genetic counseling client comes with a social history and context as well as a genetic one. Client decision-making in terms of reproductive plans, therapeutic intervention, lifestyle behavior and sharing or withholding of genetic information frequently becomes enmeshed with preexisting psycho-social relationships among biological kin, affinal kin (in-laws) and fictive kin (friends who act as family). The CEGRM makes it easier to compare different types of social interactions between the client and his/her significant others and among family members on the same dimensions. PMID- 26141157 TI - The Client's Perspective of Genetic Counseling-A Grounded Theory Study. AB - Previous studies of genetic counseling have mainly focused on outcomes defined by researchers or service providers, and have frequently related to changes in reproductive behavior and/or client knowledge. A longitudinal study of 43 families referred to a clinical genetic service was undertaken to ascertain client needs and expectations of the service, and to identify relevant outcomes from the clients' perspective. Semistructured interviews were conducted with each client, prior to and after genetic counseling. The transcribed interviews were analyzed using grounded theory. The need for certainty emerged as a powerful factor that motivated clients to pursue the genetic referral. The client's lay knowledge of the condition, satisfaction of the need for certainty, and the formation of a personalized relationship between the client and the genetics staff significantly influenced the central outcome, identified as a change in the client's psychological adaptation to the genetic condition in the family. PMID- 26141158 TI - Writing Effective Insurance Justification Letters for Cancer Genetic Testing: A Streamlined Approach. AB - The topic of insurance coverage and justification letters for cancer predisposition testing has been the subject of much discussion on the National Society of Genetic Counselors Cancer Special Interest Group (NSGC Cancer-SIG) listserv. Some counselors have stated that they have had difficulty in obtaining insurance coverage for their patients, while others have indicated that they would appreciate seeing examples of successful letters. The purpose of this paper is to provide practical guidance in writing successful letters of justification and to share insurance success stories in the area of cancer genetic testing. PMID- 26141159 TI - Genetic Library. PMID- 26141160 TI - Teaching global health with simulations and case discussions in a medical student selective. AB - BACKGROUND: Among US medical schools, demand for Global Health (GH) programs continues to grow. At the same time, cultural competency training has become a priority for medical students who will care for an increasingly diverse US patient population. We describe a pilot period for a new GH Selective designed to introduce medical students to global medicine and enhance culturally-sensitive communication skills. METHODS: As a 4-week clinical clerkship, the GH Selective was offered annually over a three-year period to a total of 33 students. Activities included clinical assignments, cultural competency and clinical skills simulations, patient case discussions in tropical medicine, journal clubs, and lectures. Faculty assessments of student performance and student evaluations of course content were focused on 6 course objectives, adapted from standardized GH objectives. RESULTS: For each offering of the GH Selective, at least 40 faculty members and fellows volunteered over 200 teaching hours from 11 medical school departments. Student feedback was consistently positive through competency-based curricular evaluations. As a result of its successes, the course is now offered on a biannual basis. DISCUSSION: Experiential, student-centered teaching employed in this course proved successful as an introduction to delivery of evidence-based and culturally sensitive GH. Special emphasis on working with standardized patients in interdisciplinary and cross-cultural simulations provided students with clinical skills applicable for care provided both locally and on international rotations. CONCLUSION: With a special emphasis on cross-cultural sensitivity, this pilot elective trained future practitioners in fund of knowledge, clinical skills, and service delivery methods in GH. PMID- 26141161 TI - Knee adduction moment relates to medial femoral and tibial cartilage morphology in clinical knee osteoarthritis. AB - The objective was to determine the extent to which the external peak knee adduction moment (KAM) and cumulative knee adductor load explained variation in medial cartilage morphology of the tibia and femur in knee osteoarthritis (OA). Sixty-two adults with clinical knee OA participated (61.5 +/- 6.2 years). To determine KAM, inverse dynamics was applied to motion and force data of walking. Cumulative knee adductor load reflected KAM impulse and loading frequency. Loading frequency was captured from an accelerometer. Magnetic resonance imaging scans were acquired with a coronal fat-saturated sequence using a 1.0 T peripheral scanner. Scans were segmented for medial cartilage volume, surface area of the bone-cartilage interface, and thickness. Forward linear regressions assessed the relationship of loading variables with cartilage morphology unadjusted, then adjusted for covariates. In the medial tibia, age and peak KAM explained 20.5% of variance in mean cartilage thickness (p<0.001). Peak KAM alone explained 12.3% of the 5th percentile of medial tibial cartilage thickness (i.e., thinnest cartilage region) (p=0.003). In the medial femur, sex, BMI, age, and peak KAM explained 44% of variance in mean cartilage thickness, with peak KAM contributing 7.9% (p<0.001). 20.7% of variance in the 5th percentile of medial femoral cartilage thickness was explained by BMI and peak KAM (p=0.001). In these models, older age, female sex, greater BMI, and greater peak KAM related with thinner cartilage. Models of KAM impulse produced similar results. In knee OA, KAM peak and impulse, but not loading frequency, were associated with cartilage thickness of the medial tibia and femur. PMID- 26141162 TI - Opportunities for measuring wheelchair kinematics in match settings; reliability of a three inertial sensor configuration. AB - Knowledge of wheelchair kinematics during a match is prerequisite for performance improvement in wheelchair basketball. Unfortunately, no measurement system providing key kinematic outcomes proved to be reliable in competition. In this study, the reliability of estimated wheelchair kinematics based on a three inertial measurement unit (IMU) configuration was assessed in wheelchair basketball match-like conditions. Twenty participants performed a series of tests reflecting different motion aspects of wheelchair basketball. During the tests wheelchair kinematics were simultaneously measured using IMUs on wheels and frame, and a 24-camera optical motion analysis system serving as gold standard. Results showed only small deviations of the IMU method compared to the gold standard, once a newly developed skid correction algorithm was applied. Calculated Root Mean Square Errors (RMSE) showed good estimates for frame displacement (RMSE<=0.05 m) and speed (RMSE<=0.1m/s), except for three truly vigorous tests. Estimates of frame rotation in the horizontal plane (RMSE<3 degrees ) and rotational speed (RMSE<7 degrees /s) were very accurate. Differences in calculated Instantaneous Rotation Centres (IRC) were small, but somewhat larger in tests performed at high speed (RMSE up to 0.19 m). Average test outcomes for linear speed (ICCs>0.90), rotational speed (ICC>0.99) and IRC (ICC> 0.90) showed high correlations between IMU data and gold standard. IMU based estimation of wheelchair kinematics provided reliable results, except for brief moments of wheel skidding in truly vigorous tests. The IMU method is believed to enable prospective research in wheelchair basketball match conditions and contribute to individual support of athletes in everyday sports practice. PMID- 26141163 TI - An Overview of Sarcopenic Obesity. AB - Sarcopenic obesity (SO) refers to the copresence of sarcopenia and obesity. In this condition, a disproportion exists between the amount of lean mass relative to fat mass. Research on SO is important because the presence of both sarcopenia and obesity may have important health consequences. However, SO research has been hampered by the disparate number of definitions of SO. Various definitions of sarcopenia include ratios of appendicular mass to height(2) or body weight, measures of muscle strength, or physical function. More recent definitions incorporate all 3. Obesity is usually defined by high body mass index, but some studies have relied on percent body fat or visceral fat. Depending on the definition, the prevalence of SO ranges from 0% to 41% in older populations. The loss of lean mass and increase in fat mass with advancing age may share common etiologic pathways. Declines in physical activity can lead to poor muscle strength, lower muscle mass, and increased fat infiltration; all of which could lead to increases in fat mass. The increases in fat mass and accompanying increases in adipokines and inflammation may further adversely affect muscle quality. SO has been related to an increased risk of mobility disability, above and beyond sarcopenia, or obesity alone. Additional research is needed to further our understanding of the pathophysiology of SO and its consequences. Interventions aimed at reducing SO may improve physical function as well as reduce disability and death. PMID- 26141165 TI - Pediatric Anesthesia-Concerns About Neurotoxicity. PMID- 26141164 TI - A qualitative analysis of peer recruitment pressures in respondent driven sampling: Are risks above the ethical limit? AB - BACKGROUND: This paper examines peer recruitment dynamics through respondent driven sampling (RDS) with a sample of injection drug users in Hartford, CT to understand the strategies participants use to recruit peers into a study and the extent to which these strategies may introduce risks above the ethical limit despite safeguards in RDS. METHODS: Out of 526 injection drug users who participated in a mixed-method RDS methodology evaluation study, a nested sample of 61 participants completed an in-depth semi-structured interview at a 2-month follow-up to explore their experiences with the recruitment process. RESULTS: Findings revealed that participants used a variety of strategies to recruit peers, ranging from one-time interactions to more persistent strategies to encourage participation (e.g., selecting peers that can easily be found and contacted later, following up with peers to remind them of their appointment, accompanying peers to the study site, etc.). Some participants described the more persistent strategies as helpful, while some others experienced these strategies as minor peer pressure, creating a feeling of obligation to participate. Narratives revealed that overall, the probability of experiencing study-related risks remains relatively low for most participants; however, a disconcerting finding was that higher study-related risks (e.g., relationship conflict, loss of relationship, physical fights, violence) were seen for recruits who participated but switched coupons or for recruits who decided not to participate in the study and did not return the coupon to the recruiter. CONCLUSIONS: Findings indicate that peer recruitment practices in RDS generally pose minimal risk, but that peer recruitment may occasionally exceed the ethical limit, and that enhanced safeguards for studies using peer recruitment methods are recommended. Suggestions for possible enhancements are described. PMID- 26141167 TI - Lack of phosphomannomutase 2 affects Xenopus laevis morphogenesis and the non canonical Wnt5a/Ror2 signalling. AB - Reduced phosphomannomutase 2 activity in man leads to hypoglycosylation of glycoconjugates causing PMM2-CDG, the most common type of congenital disorders of glycosylation. Here we show that an antisense morpholino-mediated knockdown of the Xenopus laevis phosphomannomutase 2 gene provoked a general underglycosylation in frog embryos, which led to an altered phenotype and reduced glycosylation of Wnt5a as member of the non-canonical Wnt signalling. Loss of function experiments in hemi-sectioned embryos proved that due to the phosphomannomutase 2 knockdown expression of the Wnt5a/Ror2 target gene paraxial protocadherin was significantly decreased. Regarding the expression of paraxial protocadherin, a gain of function could only be achieved by injections of wnt5a and ror2 in dorsal neighbouring blastomeres, while a parallel injection of phosphomannomutase 2 morpholino led to a significant reduced level of expression. Our data show for the first time that a knockdown of phosphomannomutase 2 influences in vivo the non-canonical Wnt signalling during early embryogenesis. PMID- 26141168 TI - Multiple splenic hamartomas and familial adenomatous polyposis: a case report and review of the literature. AB - INTRODUCTION: Splenoma or splenic hamartoma is a rare primary splenic tumor most often discovered radiologically and incidentally. Splenic hamartomas have a strong association with solid and hematological malignancies and, in rare cases, with tuberous sclerosis, but to the best of our knowledge no reports of splenic hamartomas associated with familial adenomatous polyposis have been documented, although it is recognized that familial adenomatous polyposis presents a variety of extracolonic manifestations. CASE PRESENTATION: We report on a very rare case of multiple splenic hamartomas in a 46-year-old white woman who had previously undergone surgery for restorative proctocolectomy for familial adenomatous polyposis. A computed tomography scan of her spleen revealed multiple small lesions which measured less than 1cm in diameter. A splenectomy was performed and a histologic examination of the splenectomy specimen revealed the presence of multiple hamartomas. CONCLUSION: Incidence, differential diagnosis, diagnostic procedures, pathologic findings and treatment of splenic hamartomas are discussed here and hamartomas are considered in a differential diagnosis of splenic tumors. A splenectomy is indicated in cases where malignancy cannot be excluded and in cases of associated hematologic disorders. To the best of our knowledge our patient is the first reported case to have splenic hamartomas identified in a familial adenomatous polyposis-affected patient with mutation in exon 15 of the APC gene. At this time it is not possible to correlate with certainty our multiple splenic hamartomas and familial adenomatous polyposis case as a clinical manifestation of the mutation of APC gene; however, we believe that this case report could be important for further observation of similar cases in the future. PMID- 26141169 TI - 'Big science' in the field: experimenting with badgers and bovine TB, 1995-2015. AB - Since wild badgers were first connected with outbreaks of bovine TB (bTB) in UK cattle herds in the early 1970s, the question of whether to cull them to control infections in cattle has been the subject of a protracted public and policy controversy. Following the recommendation of Prof. John Krebs that a "scientifically based experimental trial" be carried out to test the effectiveness of badger culling, the Randomised Badger Culling Trial (RBCT) was commissioned by Government in 1998. One of the largest field experiments ever conducted in the UK, the RBCT sought to recreate the conditions of a randomised controlled trial (RCT) across approximately 3000 km(2) of the South West of England. Despite widespread expectations that the RBCT would provide the necessary evidence to resolve the controversy, its findings have instead been widely contested and reinterpreted, while arguments over badger culling have become increasingly polarised. This paper will investigate the complexities of field experimental knowledge by following the story of the RBCT from this initial proposal, through processes of research design, implementation, analysis, interpretation and reinterpretation of the findings by multiple actors. It asks what kind of experiment the RBCT actually was, and examines how it has contributed to the protracted controversy over whether to cull badgers in order to control bTB in cattle. Finally, it will explore the wider implications of this case for contemporary debates over the contribution that RCTs can make to formulating public policy. PMID- 26141170 TI - Template polymerization synthesis of hydrogel and silica composite for sorption of some rare earth elements. AB - New sorbents containing 2-acrylamido 2-methyl propane sulphonic acid monomer onto poly(vinyl pyrilidone) P(VP-AMPS) hydrogel and P(VP-AMPS-SiO2) composite have been synthesized by radiation template polymerization. The effect of absorbed dose rate (kGy), crosslinker concentration and polymer/monomer ratio on the degree of template polymerization of P(VP-AMPS) hydrogel was studied. The degree of polymerization was evaluated by the calculated percent conversion and swelling degree. The maximum capacity of P(VP-AMPS) hydrogel toward Cu(+2) metal ion found to be 91 mg/gm. The polymeric composite P(VP-AMPS-SiO2) has been successfully synthesized. The structure of the prepared hydrogel and composite were confirmed by FTIR, thermal analysis (TGA and DTA) and SEM micrograph. Batch adsorption studies for La(3+), Ce(3+), Nd(3+), Eu(3+) and Pb(+2) metal ions on the prepared hydrogel and composite were investigated as a function of shaking time, pH and metal ion concentration. The sorption efficiency of the prepared hydrogel and composite toward light rare earth elements (LREEs) are arranged in the order La(3+)>Ce(3+)>Nd(3+)>Eu(3+). The obtained results demonstrated the superior adsorption capacity of the composite over the polymeric hydrogel. The maximum capacity of the polymeric composite was found to be 116, 103, 92, 76, 74 mg/gm for La(3+), Ce(3+), Nd(3+), Eu(3+) and Pb(2+) metal ions respectively. PMID- 26141171 TI - Preserved insulin sensitivity predicts metabolically healthy obese phenotype in children and adolescents. AB - Available data on metabolically healthy obese (MHO) phenotype in children suggest that gender, puberty, waist circumference, insulin sensitivity, and other laboratory predictors have a role in distinguishing these children from metabolically unhealthy obese (MUO) youth. The goal of this study was to identify predictors of MHO phenotype and to analyze glucose and insulin metabolism during oral glucose tolerance test (OGTT) in MHO children. OGTT was performed in 244 obese children and adolescents aged 4.6-18.9 years. Subjects were classified as MHO in case of no fulfilled criterion of metabolic syndrome except anthropometry or as MUO (>=2 fulfilled criteria). Among the subjects, 21.7 % had MHO phenotype, and they were more likely to be female, younger, and in earlier stages of pubertal development, with lower degree of abdominal obesity. Insulin resistance was the only independent laboratory predictor of MUO phenotype (OR 1.59, CI 1.13 2.25), with 82 % sensitivity and 60 % specificity for diagnosing MUO using HOMA IR cutoff point of >=2.85. Although no significant differences were observed in glucose regulation, MUO children had higher insulin demand throughout OGTT, with 1.53 times higher total insulin secretion. CONCLUSION: Further research is needed to investigate the possibility of targeted treatment of insulin resistance to minimize pubertal cross-over to MUO in obese children. WHAT IS KNOWN: * Substantial proportion of the obese youth (21-68 %) displays a metabolically healthy (MHO) phenotype. * Gender, puberty, waist circumference, insulin sensitivity, and lower levels of uric acid and transaminases have a possible role in distinguishing MHO from metabolically unhealthy obese (MUO) children. WHAT IS NEW: * Insulin resistance was found to be the only significant laboratory predictor of MUO when adjusted for gender, puberty, and the degree of abdominal obesity. * Besides basal insulin resistance, MUO children were found to have a significantly higher insulin secretion throughout OGTT in order to maintain glucose homeostasis. PMID- 26141173 TI - Developing Standard Recommendations (Guidelines) for Genetic Counseling Practice: A Process of the National Society of Genetic Counselors. AB - The National Society of Genetic Counselors (NSGC) supports the development of practice recommendations (guidelines) in the field of genetic counseling. This paper reviews the basic components of NSGC genetic counseling practice recommendations as well as the process for formal adoption of such documents, as approved by the Board of Directors of the NSGC. PMID- 26141172 TI - Impact of the birth's season on the development of celiac disease in Italy. AB - Celiac disease (CD) is an immune-mediated systemic disorder induced by a trigger factor in genetically susceptible individuals. There is emerging evidence about the impact of the month of birth on the development of several autoimmune diseases. Our aim was to investigate whether, in Italian CD children, the season of birth is associated with development of CD later in life. We report a survey conducted at two Italian referral centers for CD in Rome and Bari. The CD database was created to enable retrospective examination of the data of all the consecutive patients, born between 2003 and 2010, who had received a diagnosis of CD. This CD patient group comprising 596 children was compared with a reference group that included all subjects born in the same period and in the same cities (439,990 controls). Overall, there was a summer birth preponderance in CD patients compared to controls (28.2 % of CD patients vs 23.0 % of the control population; OR 1.315; 95 % CI 1.100 to 1.572). Stratifying the caseload by gender and age, the summer birth preponderance was maintained for females (28.6 % CD females vs 22.6 % control females; OR 1.368; 95 % CI 1.069 to 1.750). CONCLUSIONS: our survey confirms that in Italy, children born in summer are at higher risk to develop CD than subjects born in other seasons. The identification of a responsible seasonal factor or factors, such as timing of the first introduction of gluten and/or acute viral gastrointestinal infections, would be very important for disease prevention strategies. WHAT IS KNOWN: * Environmental factors could be involved in the pathogenesis of CD. * Data about the impact of season of birth on CD development is so far derived from North American, Northern European and Israeli surveys. WHAT IS NEW: * This is the first study in Southern Europe to find a relationship between season of birth (summer) and development of CD. * Summer-born infants are introduced to complementary feeding (gluten) in winter, when the rotavirus infection is at its highest peak; this may be the link between season of birth and development of CD. PMID- 26141174 TI - Review Article: Chiari Type I Malformation with or Without Syringomyelia: Prevalence and Genetics. AB - Chiari type I malformation has traditionally been defined as a downward herniation of the cerebellar tonsils of >=5 mm through the foramen magnum and it is likely associated with a volumetrically reduced posterior fossa. Syringomyelia is commonly associated with Chiari type I malformation. We estimate the prevalence of these two conditions and determine that they are more common than previously expected. We identify the genetic syndromes associated with some cases of Chiari type I malformation, and we provide evidence in favor of a genetic hypothesis for at least a subset of the nonsyndromic cases. PMID- 26141176 TI - Genetic Library. PMID- 26141175 TI - Subjective and Objective Risks of Carrying a BRCA1/2 Mutation in Individuals of Ashkenazi Jewish Descent. AB - This repeated measures study examines (1) the change in subjective risk of mutations pre- to postcounseling, (2) the accuracy of BRCAPRO estimates of mutations, and (3) the discrepancy between subjective risk and BRCAPRO estimates of mutations before and after genetic counseling. Ninety-nine Ashkenazi Jewish individuals pursued testing for BRCA1/2 mutations. Most had a personal cancer history (N = 51; family only: N = 48); and received uninformative negative results (N = 66; positives: N = 23; informative negative: N = 10). The coping strategy of defensive pessimism predicts that individuals will believe the worst case scenario to better cope with a potential negative outcome. Consistent with this, most felt they would have a mutation, if not mutations in both genes. The BRCAPRO model appeared to overestimate risk of having a mutation in this sample (p < .001). BRCAPRO overestimates notwithstanding, genetic counseling increased accuracy of subjective risk (p < .01). Individuals with a family-only cancer history had the least accurate estimates of risk (p < .05) and may need further intervention to either manage anxiety or improve knowledge. PMID- 26141177 TI - Comprehensive diagnostics in a case of hereditary diffuse leukodystrophy with spheroids. AB - BACKGROUND: Hereditary diffuse leukodystrophy with spheroids is a rare type of leukoencephalopathy. Mutations in the colony stimulating factor 1 receptor have recently been identified to be the cause of this microgliopathy. Clinical and radiological presentation can often misguide physicians during the diagnosis of patients with this underdiagnosed disease. CASE PRESENTATION: We present a 29 year-old woman with a rapid course of hereditary diffuse leukodystrophy with spheroids. She mainly showed cognitive impairment and severe motor dysfunctions. Her MRI showed spotted and confluent hyperintensities of the white matter on T2 weighted images involving the corticospinal tract as well as the corpus callosum. Further, those lesions showed striking restricted diffusion. As this restricted diffusion in all areas showing signs of leukoencephalopathy was so impressive we searched Medline for these terms and got hereditary diffuse leukodystrophy with spheroids as one of the first results. After a comprehensive diagnostic workup and exclusion of other leukoencephalopathies, stereotactic biopsy and genetic testing confirmed the diagnosis. CONCLUSION: This case points out at two important features of hereditary diffuse leukodystrophy with spheroids being spotted and/or confluent leukoencephalopathy with areas of restricted diffusion. This might help to identify more patients with this underdiagnosed disease. Moreover, the rapid clinical course in our patient raises the question whether the relatively pronounced areas of restricted diffusion are indicative of a more acute progression of the disease. PMID- 26141178 TI - Lowering diastolic blood pressure in non-proteinuric hypertension in pregnancy is not harmful to the fetus and is associated with reduced frequency of severe maternal hypertension. PMID- 26141179 TI - Physical activity may improve measures of cognition in children. PMID- 26141180 TI - Coronary artery bypass surgery continues to remain the treatment of choice for multivessel coronary artery disease even in the era of new-generation drug eluting stents. PMID- 26141181 TI - US vaccine researcher is jailed for fraud. PMID- 26141183 TI - The long-term results of double switch operation and functional repair for congenitally corrected transposition of the great arteries. PMID- 26141182 TI - From rest to stressed: endothelin-1 levels in young healthy smokers and non smokers. AB - INTRODUCTION: Endothelin-1 (ET-1) is a potent vasoconstrictor produced by vascular endothelial cells, and a known marker of endothelial dysfunction. However, the acute and chronic effects of smoking and nicotine gum on the ET-1 response to acute physical stress in young healthy smokers have not been investigated. METHODS: Healthy smokers (n=35) and non-smokers (n=35) underwent an exercise test to exhaustion (maximal oxygen consumption) on a treadmill. Smokers were assessed a) after 12h smoking abstinence (termed chronic smoking), b) immediately after smoking one cigarette (termed acute smoking), and c) immediately after chewing nicotine gum. Blood was drawn immediately pre-exercise, and 3 minutes post-exercise. During exercise, cardiorespiratory parameters were obtained breath-by-breath using an automated metabolic cart. Plasma ET-1 levels were quantified using enzyme-linked immunosorbent-assay. The above protocol was designed to incorporate exercise as a vascular stressor to reveal changes that would not be detected at rest. RESULTS: Mean age was 28.6+/-7.2 years and body mass index (BMI) was 23.6+/-3.2 kg/m(2). Post-exercise ET-1 levels were significantly lower than pre-exercise levels in non-smokers (P<0.001) and smokers under all three conditions (P=0.005, P<0.001, P=0.001, respectively). There were no differences in post-exercise ET-1 levels between non-smokers and smokers under all three conditions, however the absolute and relative decrease in ET-1 levels was significantly smaller in chronic smokers compared with non-smokers (P=0.007 and P=0.004). Chronic smokers had a significantly lower exercise-induced change in tidal volume (P=0.050), fraction of expired CO2 (P=0.021), oxygen consumption (P=0.005), carbon dioxide elimination (P=0.004) and peak expiratory flow (P=0.003) compared with non-smokers. Furthermore, the decrease in ET-1 observed in non-smokers in response to exercise was significantly associated with exercise induced-changes in inspiratory time, time for a tidal volume cycle, respiratory frequency, inspired minute ventilation and peak inspiratory flow. CONCLUSIONS: An acute decrease of circulating ET-1 in response to acute maximal exercise in young healthy individuals was noted. Chronic smokers had a significantly diminished decrease in ET-1 compared with non-smokers, however there were no significant differences in the ET-1 response between smokers under the three smoking conditions. Smokers were not able to achieve the same exercise-induced changes in cardiorespiratory parameters as non-smokers. By incorporating exercise as a vascular stressor in our study, we have taken a novel approach to provide evidence of an altered ET-1 and cardiorespiratory response that would not otherwise be observed at rest in young active healthy smokers. PMID- 26141184 TI - The Role of Expectations in Effective Genetic Counseling. AB - The goals for this investigation were to assess individuals' expectations for social support from genetic counselors, and to explore how these expectations influence perceptions of genetic counselor effectiveness. Two studies were conducted to address these goals. Results from the first study show that individuals most frequently expect genetic counselors to provide options and support following the disclosure of distressing test results, while data from the second study demonstrate that expectations play a significant role in individuals' assessment of genetic counselor effectiveness. These findings shed light on what individuals expect from genetic counselors following the disclosure of medically positive test results and inform how these expectations influence the success of genetic counseling sessions. PMID- 26141185 TI - A Method for Analyzing Videotaped Genetic Counseling Sessions. AB - This study describes the development and evaluation of a multi-item scale for analyzing the genetic counseling process, the Manchester Observation Code (MOC) for genetic counseling. The instrument is specific to the field of genetic counseling and is designed for analysis of the communication between counselor and client. Coding is done directly from videotaped sessions. Because communication is the means by which genetic counseling is accomplished, the method measures four relevant components of communication: (1) grammatical form, (2) purpose, (3) subject, and (4) cue source. The instrument enables an observer to code the counselor's statements into these four components. Three videotaped sessions were used to measure interrater reliability, or the consistency of rating for each of the four communication domains using this method. Three videotaped sessions were also used to measure test-retest reliability, or the consistency of the designed method from one time to another. A total of 21 videotaped sessions were tested using the method. A statistical measure of reliability established consistency of the designed method; Cohen's kappa yielded 0.7 for interrater reliability and 0.79 for test-retest reliability. These findings suggest this instrument may be used to identify important elements of the genetic counseling process. PMID- 26141187 TI - Genetic Library. PMID- 26141186 TI - An Opportunity for Genetic Counseling Intervention: Depression in Parents of Individuals with Proteus Syndrome. AB - Depression is common, affecting 2-5% of the general population. Parental depression can confound adjustment to, and caring for, a child with a genetic condition. As part of a study on psychosocial issues of parents caring for children with Proteus syndrome, 31 parents (20 mothers and 11 fathers) completed a depression screening tool, the Beck Depression Inventory. Approximately 23% (4/20 mothers and 3/11 fathers) scored positive on the tool. Pessimism, sense of failure, general lack of satisfaction, sense of punishment, self-dislike, social withdrawal, indecisiveness, work inhibition, somatic preoccupation, and loss of libido were reported more frequently by the group of parents with positive screen results than those with normal results. These data suggest that symptoms of depression may be prevailing among parents of individuals with Proteus syndrome. Because effective interventions for depression are readily available, genetic counselors working with families affected with rare, overgrowth disorders should specifically assess parents for physical and affective symptoms of depression and refer them for appropriate clinical treatment. PMID- 26141188 TI - A comparison of fallout (236)U and (239)Pu uptake by Australian vegetation. AB - The isotopes (236)U and (239)Pu, both produced during nuclear weapons tests carried out in the 1950s and 1960s, are present in the environment and may be used as tracers for soil erosion studies. Although these radionuclides occur only at ultra-trace levels in nature, they can be readily measured by accelerator mass spectrometry with the 14UD heavy ion accelerator at the Australian National University. We have analysed a series of vegetation samples for their (236)U and (239)Pu concentration and compared the results with those found in the surrounding soil. (236)U could be measured in all collected samples whereas (239)Pu could not be detected in several vegetation samples due to its very low concentration, although it was readily detectable in the soil. We find that, relative to plutonium, (236)U is preferentially taken up by plants with enrichment factors ((236)U/(239)Pu)veg/((236)U/(239)Pu)soil that range between 7 and 52 in the present study. PMID- 26141189 TI - (236)U and (239,)(240)Pu ratios from soils around an Australian nuclear weapons test site. AB - The isotopes (236)U, (239)Pu and (240)Pu are present in surface soils as a result of global fallout from nuclear weapons tests carried out in the 1950's and 1960's. These isotopes potentially constitute artificial tracers of recent soil erosion and sediment movement. Only Accelerator Mass Spectrometry has the requisite sensitivity to measure all three isotopes at these environmental levels. Coupled with its relatively high throughput capabilities, this makes it feasible to conduct studies of erosion across the geographical extent of the Australian continent. In the Australian context, however, global fallout is not the only source of these isotopes. As part of its weapons development program the United Kingdom carried out a series of atmospheric and surface nuclear weapons tests at Maralinga, South Australia in 1956 and 1957. The tests have made a significant contribution to the Pu isotopic abundances present in the region around Maralinga and out to distances ~1000 km, and impact on the assessment techniques used in the soil and sediment tracer studies. Quantification of the relative fallout contribution derived from detonations at Maralinga is complicated owing to significant contamination around the test site from numerous nuclear weapons safety trials that were also carried out around the site. We show that (236)U can provide new information on the component of the fallout that is derived from the local nuclear weapons tests, and highlight the potential of (236)U as a new fallout tracer. PMID- 26141190 TI - An adjustable fetal weight standard for twins: a statistical modeling study. AB - BACKGROUND: It is a common practice to use a singleton fetal growth standard to assess twin growth. We aim to create a twin fetal weight standard which is also adjustable for race/ethnicity and other factors. METHODS: Over half a million twin births of low risk pregnancies in the US, from 1995 to 2004, were used to construct a fetal weight standard. We used the Hadlock's fetal growth standard and the proportionality principle to make the standard adjustable for other factors such as race/ethnicity. We validated the standard in different race/ethnicities in the US and against previously published curves from around the world. RESULTS: The adjustable fetal weight standard has an excellent match with the observed birthweight data in non-Hispanic White, non-Hispanic Black, Hispanics, and Asian from 24 to 38 weeks gestation. It also had a very good fit with cross-sectional data from Australia and Norway, and a longitudinal standard from Brazil. However, our model-based 10th and 90th percentiles differed substantially from studies in Japan and US that used the last menstrual period for estimate of gestational age. CONCLUSION: The adjustable fetal weight standard for twins is a flexible tool and can be used in different populations. PMID- 26141191 TI - The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice. AB - RATIONALE: Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice. OBJECTIVE: We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy. METHODS: Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer assisted microdensitometry and corrected for non-specific binding. RESULTS: Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75% receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection. CONCLUSIONS: Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone. PMID- 26141192 TI - Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features. AB - RATIONALE: Bipolar disorder (BD) is a disabling and life-threatening disease characterized by states of depression and mania. New and efficacious treatments have not been forthcoming partly due to a lack of well-validated models representing both facets of BD. OBJECTIVES: We hypothesized that cholinergic- and dopaminergic-pharmacological manipulations would model depression and mania respectively, each attenuated by lithium treatment. METHODS: C57BL/6 J mice received the acetylcholinesterase inhibitor physostigmine or saline before testing for "behavioral despair" (immobility) in the tail suspension test (TST) and forced swim test (FST). Physostigmine effects on exploration and sensorimotor gating were assessed using the cross-species behavioral pattern monitor (BPM) and prepulse inhibition (PPI) paradigms. Other C57BL/6 J mice received chronic lithium drinking water (300, 600, or 1200 mg/l) before assessing their effects alone in the BPM or with physostigmine on FST performance. Another group was tested with acute GBR12909 (dopamine transporter inhibitor) and chronic lithium (1000 mg/l) in the BPM. RESULTS: Physostigmine (0.03 mg/kg) increased immobility in the TST and FST without affecting activity, exploration, or PPI. Lithium (600 mg/l) resulted in low therapeutic serum concentrations and normalized the physostigmine-increased immobility in the FST. GBR12909 induced mania-like behavior in the BPM of which hyper-exploration was attenuated, though not reversed, after chronic lithium (1000 mg/ml). CONCLUSIONS: Increased cholinergic levels induced depression-like behavior and hyperdopaminergia induced mania-like behavior in mice, while chronic lithium treated some, but not all, facets of these effects. These data support a cholinergic-monoaminergic mechanism for modeling BD aspects and provide a way to assess novel therapeutics. PMID- 26141194 TI - Role of EphA4 signaling in the pathogenesis of amyotrophic lateral sclerosis and therapeutic potential of traditional Chinese medicine rhynchophylline. PMID- 26141193 TI - Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats. AB - RATIONALE: The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. OBJECTIVE: The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. METHODS: In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. RESULTS: Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. DISCUSSION: These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors. PMID- 26141195 TI - The existence of cords in olecranon bursae. AB - BACKGROUND: The purpose of this study was to document the existence of transverse cords in olecranon bursae in patients undergoing excision of the bursa and to describe the unique clinical presentation of patients with these cords. METHODS: A retrospective study was performed on 24 patients who had surgery to excise an olecranon bursa between 2006 and 2011. The patient's history, preoperative radiographs, ultrasound images, intraoperative photographs, and findings on histologic analysis were reviewed in all cases. RESULTS: Nine olecranon bursae had cords (cord group) and 15 did not have cords (noncord group). All patients in the cord group were male manual laborers, and nearly all had olecranon enthesophytes (n = 8). Patients in the noncord group had associated medical conditions or an infection. A higher level of satisfaction was reported in the noncord group after surgical excision. CONCLUSION: This study documents the existence of transverse cords oriented at right angles to the long axis of the olecranon. Olecranon bursae with cords have a unique presentation and are found in male manual workers, are nearly always associated with an olecranon enthesophyte, and do not present with infections. PMID- 26141196 TI - Demographic trends in arthroscopic and open biceps tenodesis across the United States. AB - BACKGROUND: The purpose of this study was to evaluate trends in procedures and to report on demographic data of patients undergoing arthroscopic vs. open biceps tenodesis. METHODS: A retrospective review of a commercially available database (PearlDiver) was conducted to identify cases of arthroscopic and open biceps tenodesis performed between 2007 and 2011 with concurrent diagnoses of commonly associated shoulder disorders. Each record provided the patient's age, gender, and region within the United States, and statistical significance was determined with respect to each of these demographics. RESULTS: There were 9011 patients who underwent arthroscopic biceps tenodesis and 11,678 patients who underwent open biceps tenodesis between 2007 and 2011. The number of biceps tenodesis cases increased from 2007 to 2011 (2047 to 5832; P = .015). Both arthroscopic and open biceps tenodesis procedures were performed most commonly in the 30- to 59-year old age group (76.3% and 76.1%; P < .00001). Men underwent arthroscopic or open biceps tenodesis more commonly than women did (66.1% and 71.9%; P < .00001). Rates of both open and arthroscopic biceps tenodesis varied significantly among the Midwest, South, Northeast, and West regions (P = .009; P = .007); 49.8% of arthroscopic and 44.6% of open biceps tenodesis cases were associated with rotator cuff tears, whereas 14.4% of arthroscopic and 16.2% of open cases were associated with biceps tendon disorders. CONCLUSION: Both arthroscopic and open biceps tenodesis cases increased annually from 2007 to 2011. The majority of biceps tenodesis cases were performed in men aged 30 to 59 years, and the South had the highest overall number of cases. Further studies are required to evaluate the efficacy of these procedures with and without concomitant pathologic processes. PMID- 26141197 TI - Tuberosity healing after reverse shoulder arthroplasty for acute proximal humerus fractures: the "black and tan" technique. AB - BACKGROUND: Reverse shoulder arthroplasty has seen increased use for management of complex proximal humeral fractures in the elderly. Recent evidence has shown that tuberosity healing leads to improved active range of motion and functional outcomes. The purpose of this study was to report on the radiographic and clinical outcomes of a consecutive series of patients having undergone reverse shoulder arthroplasty for fracture utilizing the "black and tan" method--a hybrid cementation-impaction grafting technique that uses autogenous cancellous bone graft to create an interface between the proximal cement mantle and the area of tuberosity repair. METHODS: Twenty-five patients (average age, 77 years; range, 63-88 years) were included in the analysis with a mean follow-up of 17 months. All patients underwent reverse shoulder arthroplasty for a complex proximal humerus fracture using the black and tan technique. RESULTS: The tuberosity healing rate was 88%. At final follow-up, mean active elevation was 117 degrees +/- 23 degrees , mean abduction was 86 degrees +/- 16 degrees , and mean external rotation was 29 degrees +/- 18 degrees . External rotation strength averaged 4.9 +/- 0.2. The Simple Shoulder Test and Single Assessment Numeric Evaluation scores averaged 7 and 76, respectively. The mean American Shoulder and Elbow Surgeons total score was 71; visual analog scale score for pain, 2; and visual analog scale score for function, 7. Of the 25 patients, 21 (84%) rated their satisfaction with the surgery as excellent or good. CONCLUSIONS: The black and tan technique together with standard suture repair and an implant with features that support tuberosity repair results in a high tuberosity healing rate with restoration of external rotation after reverse shoulder arthroplasty for fracture. PMID- 26141198 TI - Exploring Mexican American adolescent romantic relationship profiles and adjustment. AB - Although Mexican Americans are the largest ethnic minority group in the nation, knowledge is limited regarding this population's adolescent romantic relationships. This study explored whether 12th grade Mexican Americans' (N = 218; 54% female) romantic relationship characteristics, cultural values, and gender created unique latent classes and if so, whether they were linked to adjustment. Latent class analyses suggested three profiles including, relatively speaking, higher, satisfactory, and lower quality romantic relationships. Regression analyses indicated these profiles had distinct associations with adjustment. Specifically, adolescents with higher and satisfactory quality romantic relationships reported greater future family expectations, higher self esteem, and fewer externalizing symptoms than those with lower quality romantic relationships. Similarly, adolescents with higher quality romantic relationships reported greater academic self-efficacy and fewer sexual partners than those with lower quality romantic relationships. Overall, results suggested higher quality romantic relationships were most optimal for adjustment. Future research directions and implications are discussed. PMID- 26141199 TI - Left Ventricular Noncompaction Diagnosis and Management Relevant to Pre participation Screening of Athletes. AB - Left ventricular noncompaction (LVNC) has been extensively studied over the last years, and an increasing number of cases have been reported worldwide, with a large proportion comprising young and asymptomatic subjects, including athletes. The current epidemic of LVNC is likely the consequence of several causes, that is, the increased awareness of the disease and the refined cardiovascular imaging techniques. The current diagnostic methods, based uniquely on definition of morphologic findings, do not always resolve the overlap of a physiological myocardial architecture comprising a prominent trabecular pattern from a mild phenotypic expression of the real disease. Appropriate criteria for identification and management of LVNC in athletes have, therefore, become a novel challenge for cardiologists and sport physicians, who are required to solve the question of diagnosis and appropriate management in the setting of pre participation cardiovascular screening. Indeed, although it is important to timely identify a true myocardial disease, to reduce the burden of adverse cardiac event in a young athlete, in contrast, a misdiagnosis of LVNC may lead to unwarranted restriction of the athlete lifestyle, with detrimental psychological, social, and economic consequences. This review report has been planned, therefore, to help physicians in diagnosing and managing athletes presenting with a morphologic pattern suggestive of LVNC with specific focus on criteria for advising sport participation. PMID- 26141200 TI - Coffee Consumption and Cardiovascular Health. AB - Coffee is the most widely consumed beverage worldwide and is only second to water drinking and is consumed by 83% of adults in the United States. The long-held controversy regarding the association of coffee consumption with an increased incidence of cardiovascular diseases (CVDs) and hypertension has been reversed by several recent prospective cohort studies and meta-analyses, which have demonstrated that coffee consumption is not associated with increased incidence of CVDs and hypertension and instead it could have a beneficial effect. To get a better understanding of the effects of coffee consumption on cardiovascular health, a Medline search of the English language literature was conducted from 2010 to early 2015 and 25 pertinent reports with information on the effects of coffee drinking, the incidence of CVDs, and hypertension and its mechanism of action were selected for inclusion in this commentary. These studies have shown either a neutral or beneficial effect of coffee on cardiovascular health. In conclusion, coffee is safe to drink by both normal subjects and by those with preexisting CVDs and hypertension. PMID- 26141201 TI - Phosphodiesterase 5 Inhibitor Use in Men With Hypertrophic Cardiomyopathy. AB - The prevalence of sexual dysfunction (SD) in men with hypertrophic cardiomyopathy (HC) remains unknown, yet its clinical relevance may be high given that its treatment-phosphodiesterase 5 inhibitors (PDE5i)-can increase the left ventricular outflow tract pressure gradient. In this retrospective study, we evaluated the medical records of consecutively seen men with HC for the evidence of SD (defined as SD diagnosis noted in the medical record, the use of medications unique for SD, or SD reported by the patient on a routine clinical questionnaire). Of the 283 consecutively seen men with HC (mean age 52.9 +/- 14.1 years), 63 patients (22%) with SD were identified. Of those with SD, 38% were recorded as regularly using PDE5i. In conclusion, SD and the use of PDE5i present a relatively common occurrence in men with HC, and further studies are needed to develop an evidence-guided algorithm for safe implementation of SD therapies in this most common inherited cardiomyopathy. PMID- 26141202 TI - Inferior Q Waves and Left Bundle Branch Block. PMID- 26141203 TI - Act Healthy: promoting health behaviors and self-efficacy in the workplace. AB - Chronic health conditions and multiple health risk factors afflict Americans and burden employers, but effective, affordable, workplace-based health promotion interventions have not been widely implemented. This is the first study to adapt the empirically validated Chronic Disease Self-Management Program for a general employee population in a workplace setting with an emphasis on disease prevention and health promotion. A quasi-experimental, wellness standard of care comparison, prospective cohort design was used among employee participants at a large University employer. Ninety-one individuals participated in the program. Participants reported significantly increased health behavior frequency and self efficacy after the intervention, compared with their pre-intervention scores, and improvements were sustained at 3-month follow-up [self-rated abilities for health practices scale (SRA): F = 30.89, P < 0.001; health promoting lifestyle profile II (HPLP-II): F = 36.30 P < 0.001]. Individuals in the intervention group reported improved self-efficacy and health behaviors compared with the wellness standard of care comparison group at post intervention (SRA: F = 12.45, P < 0.001; HPLP-II: F = 25.28, P < 0.001). Adapting lay-facilitated self-management for the workplace offers promise as a replicable, scalable, affordable model for culture change in organizations. PMID- 26141204 TI - Primary mantle cell lymphoma of the nasopharynx: a rare clinical entity. PMID- 26141205 TI - Evaluation of cytokines produced by beta-hemolytic streptococcus in acute pharyngotonsillitis. AB - INTRODUCTION: The most common pathogen in bacteria lpharyngotonsillitis is group A beta-hemolytic streptococcus, although groups B, C, F,and G have also been associated with pharyngotonsillitis. OBJECTIVE: To assess the levels of the cytokines TNF-alpha, IL-6,IL-4, and IL-10 in bacterial pharyngotonsillitis caused by group A and non-A (groups B, C, F and G) beta-hemolytic streptococcus. METHODS: The study was conducted at a pediatric emergency care unit. The sample comprised children (5-9 years old) with acute bacterial pharyngotonsillitis diagnosed between December of 2011 and May of 2012. The research involved collection of blood samples from the patients, enzyme-linked immunosorbent assay detection of TNF-alpha, IL-6,IL-4, and IL-10, and collection of two oropharyngeal swabs for bacterial isolation. Additionally, the medical history of the study participants was also collected. RESULTS: In the studied group (mean age: 5.93 years), higher pharyngotonsillitis incidence was observed in the female gender (64.76%). Higher incidence of tonsillar exudates was observed with groups A and C. No statistically significant differences in cytokine levels were observed among groups. However, the group A and the control group showed a difference in the IL-6 level (p=0.0016). CONCLUSIONS: The Groups A and C showed higher cytokine levels than the Groups B and control, suggesting similar immunological patterns. PMID- 26141206 TI - Peritumoral infiltrate in the prognosis of epidermoid carcinoma of the oral cavity. AB - INTRODUCTION: Patients with squamous cell carcinoma of the oral cavity present deficits in their cellular immunity that contribute to neoplastic growth. Thus, the inflammatory activity, such as the immunological response to the tumor, can be used as a prognostic factor. OBJECTIVES: To evaluate the correlation between peritumoral inflammation and clinical characteristics of the patients, survival, and the disease-free interval. METHODS: The study sample consisted of a retrospective hospital-based cohort of patients undergoing surgery for resection of oral cavity tumor. The inflammatory infiltrate on the slides was evaluated semi-quantitatively, and were divided into minor and major inflammatory processes. RESULTS: This study included 57 tumor samples, with infiltration of lymphocytes, plasma cells, and histiocytes. The log-rank test showed no significance for the survival curves and recurrence of the "minor inflammatory" and "major inflammatory" processes, with p=0.14 and p=0.24, respectively. A direct association between age and inflammation (p=0.04) was observed, as well as an indirect association between the degree of tumor differentiation and inflammation (p=0.01). CONCLUSION: Although associated with histological differentiation, the peritumoral inflammatory process cannot be considered a prognostic factor in squamous cell carcinoma of the oral cavity, as it is not related to survival and disease-free interval. PMID- 26141207 TI - Visual loss: a rare complication of maxillary sinus mucocele. PMID- 26141208 TI - Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). AB - BACKGROUND: The OPTIMAL study was the first study to compare efficacy and tolerability of the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) erlotinib, versus standard chemotherapy in first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Findings from final overall survival (OS) analysis and assessment of post-study treatment impact are presented. PATIENTS AND METHODS: Of 165 randomised patients, 82 received erlotinib and 72 gemcitabine plus carboplatin. Final OS analyses were conducted when 70% of deaths had occurred in the intent-to treat population. Subgroup OS was analysed by Cox proportional hazards model and included randomisation stratification factors and post-study treatments. RESULTS: Median OS was similar between the erlotinib (22.8 months) and chemotherapy (27.2 months) arms with no significant between-group differences in the overall population [hazard ratio (HR), 1.19; 95% confidence interval (CI) 0.83-1.71; P = 0.2663], the exon 19 deletion subpopulation (HR, 1.52; 95% CI 0.91-2.52; P = 0.1037) or the exon 21 L858 mutation subpopulation (HR, 0.92; 95% CI 0.55-1.54; P = 0.7392). More patients in the erlotinib arm versus the chemotherapy arm did not receive any post-study treatment (36.6% versus 22.2%). Patients who received sequential combination of EGFR-TKI and chemotherapy had significantly improved OS compared with those who received EGFR-TKI or chemotherapy only (29.7 versus 20.7 or 11.2 months, respectively; P < 0.0001). OS was significantly shorter in patients who did not receive post-study treatments compared with those who received subsequent treatments in both arms. CONCLUSION: The significant OS benefit observed in patients treated with EGFR-TKI emphasises its contribution to improving survival of EGFR mutant NSCLC patients, suggesting that erlotinib should be considered standard first-line treatment of EGFR mutant patients and EGFR-TKI treatment following first-line therapy also brings significant benefits to those patients. CLINICALTRIALSGOV IDENTIFIER: NCT00874419. PMID- 26141209 TI - Diurnal patterns of objectively measured physical activity and sedentary behaviour in older men. AB - BACKGROUND: Physical activity (PA) levels among older adults are generally low and sedentary behaviour (SB) very common; increasing PA and reducing SB levels could have appreciable health benefits. Quantifying PA and SB patterns through the day could help in defining strategies for change. We examined within day variations in PA and SB and whether these varied by demographic factors and health status. METHODS: Men aged 71-91 years participating in an established UK population-based cohort study were invited to wear a GT3x Actigraph accelerometer over the hip for one week in 2010-12. Percentages of time spent in sedentary (SB, <100 counts per minute [CPM]); in light (LIPA, 100-1040 CPM) and in moderate to vigorous PA (MVPA, >1040 CPM) were derived. Multilevel models were used to estimate the associations between demographic factors and health status and SB, LIPA and MVPA. RESULTS: 1455 of 3137 men invited (46.4 %) participated and provided adequate data. Men spent 73 % of the day in SB, 23 % in LIPA and 4.5 % in MVPA (619, 197 and 39 min per day respectively). The percentage of time spent in MVPA was highest in the morning, peaking at 10-11 am (8.4 %), and then declining until the evening, with the exception of a small increase at 2-3 pm. LIPA followed a similar pattern. Conversely, SB levels were lowest in the morning and increased throughout the day, peaking at 9 pm (88 %). Men who were older, did not use active transport, had mobility limitations, were obese, depressed, had more chronic health conditions, and were smokers had lower levels of MVPA. The impacts of older age, obesity, mobility limitations and chronic diseases on LIPA, MVPA and SB were more marked in the morning than in the afternoon and evening. CONCLUSIONS: Levels of MVPA and LIPA are highest in the morning (peak at 10-11 am) and decrease during the day. SB increases through the course of the day to peak in the evening. Interventions to encourage older men to be physically active may need to take account of current PA patterns, aiming to prolong active morning bouts of PA and/or reducing SB in the afternoon and evening hours. PMID- 26141210 TI - Accelerated resolution therapy: an innovative mental health intervention to treat post-traumatic stress disorder. AB - Post-traumatic stress disorder (PTSD) is a disabling trauma and stress-related disorder that may occur after a person experiences a traumatic event, and evokes a combination of intrusion and avoidance symptoms, negative alterations in cognitions and mood, and alterations in arousal and reactivity. Accelerated resolution therapy (ART) is an emerging psychotherapy that provides fast and lasting resolution for mental health problems such as PTSD. ART has been shown to achieve a positive result in one to five sessions, typically over a 2-week period, and requires no homework, skills practice or repeated exposure to targeted events. Initial research, including one randomised control trial, has demonstrated that ART interventions can significantly reduce symptoms of psychological trauma in both civilians and US service members and veterans. These results suggest that ART be considered as either a primary treatment option or for refractory PTSD in those with a suboptimal response to endorsed first-line therapies. Conservative estimates indicate substantial potential cost savings in PTSD treatment. Despite the need for more definitive clinical trials, there is increasing interest in ART in the USA, including in the US Army. The growing positive empirical evidence is compelling, and there appears to be sufficient evidence to warrant UK researchers undertaking ART research. The armed forces offer the potential for comparative international trials. However, equally important are veterans, emergency services personnel and those subjected to violence. ART appears to also have application in other conditions, including depression, anxiety disorders, and alcohol or drug misuse. ART can potentially help personnel traumatised by the unique challenges of war and conflict zones by providing brief psychotherapy in a readily accessible and culturally competent manner. ART facilitates the provision of interventions and resolutions in theatre, thus enhancing forces' fighting capability. PMID- 26141211 TI - A case of an avoidable admission to an Ebola treatment unit with malaria and an associated heat illness. AB - We present a 27-year old British nurse admitted to the Kerry Town Ebola Treatment Unit, Sierra Leone, with symptoms fitting suspect-Ebola virus disease (EVD) case criteria. A diagnosis of Plasmodium falciparum malaria and heat illness was ultimately made, both of which could have been prevented through employing simple measures not utilised in this case. The dual pathology of her presentation was atypical for either disease meaning EVD could not be immediately excluded. She remained isolated in the red zone until 72 h from symptom onset. This case highlights why force protection measures are important to reduce the incidence of both malaria and heat illness in deployed military and civilian populations. These prevention measures are particularly pertinent during the current EVD epidemic where presenting with these pathologies requires clinical assessment in the 'red zone' of an Ebola treatment unit. PMID- 26141212 TI - Cytogenetic Impact on Lenalidomide Treatment in Relapsed/Refractory Multiple Myeloma: A Real-Life Evaluation. AB - INTRODUCTION: In this retrospective real-life study in relapsed/refractory multiple myeloma patients, we analyzed clinical and biologic features distinguishing patients with rapidly progressing disease while receiving lenalidomide therapy from those without progression. PATIENTS AND METHODS: According to time of stopping lenalidomide, patients were subdivided into 3 groups: early stop (ES) (n = 23), when therapy was discontinued within 6 months; intermediate (INT) (n = 23), when therapy was stopped between 7 to 24 months; and long survival (LS) (n = 45), when therapy was maintained for more than 2 years. The median age of the whole cohort was 70 years (range, 42-85 years); 40% had an International Staging System score of 2 or 3. RESULTS: High-risk cytogenetic findings, including 1q gain, was reported in 65% ES, 43% INT, and 21% LS. Overall response rate was 63%, with median progression-free survival and overall survival of 33 and 56 months, respectively. CONCLUSION: Although high-risk cytogenetic findings negatively affect progression-free survival and overall survival, 28% of cytogenetic high-risk patients experienced long survival, provided that lenalidomide therapy was not discontinued, thus pointing to the role of maintenance therapy in this subset of patients. PMID- 26141213 TI - Jumping Translocations in Myeloid Malignancies Associated With Treatment Resistance and Poor Survival. AB - BACKGROUND: Jumping translocations (JT) are uncommon cytogenetic abnormalities involving nonreciprocal translocations of a single donor chromosome onto 2 or more chromosomes. The clinical characteristics and prognosis of JTs in patients with myeloid malignancies are not well described. MATERIALS AND METHODS: We searched our cytogenetic database from 2003 to 2014 to identify cases of myeloid malignancies associated with a JT. These cases were cross-referenced with our clinical databases to determine patient characteristics, response to treatment and overall survival. RESULTS: We identified 10 patients with myeloid malignancies and a JT: 4 cases of acute myeloid leukemia with myelodysplastic syndrome-related changes, 4 cases of myelodysplastic syndrome, and 2 cases of postpolycythemia myelofibrosis. The donor segment was derived from chromosome 1 in every case. The acquisition of a JT was a late occurrence, with a median time to JT development of 24.9 months (range, 0-248 months) from diagnosis. The overall response to treatment was poor, with no patients experiencing a response to conventional chemotherapy or hypomethylating agents. The median overall survival for the group was 9 months (95% confidence interval, 2.5-15.5) after identification of a JT. CONCLUSION: The acquisition of a JT in patients with myeloid malignancies appears to be a late event and is associated with myelodysplasia. In our series, this was associated with a poor prognosis with a poor response to treatment, disease transformation to acute myeloid leukemia, and short overall survival. PMID- 26141214 TI - Outpatient Autologous Stem Cell Transplantation for Patients With Myeloma. AB - BACKGROUND: High-dose melphalan with autologous stem cell support improves survival for patients with myeloma. For selected patients, we have been using a protocol of short hospitalization, discharging patients to home with careful outpatient monitoring in the office, which we hypothesized would reduce complications and utilization of inpatient beds. METHODS: We reviewed 301 initial autologous transplants for myeloma, categorized as brief stay (<= 4 days, 82 patients) or prolonged stay (>= 5 days, 219 patients). Selection for a brief stay was determined by clinical characteristics, availability of caregivers at home, distance from our medical center, and patient preference. RESULTS: Within the brief stay population, 67% required readmission before day + 100, but this group still had fewer cumulative hospital days (9 vs. 18, P < .0001). There were fewer documented infections among brief stay patients (22% vs. 46% P < .001) and fewer admissions to intensive care units (0% vs. 5.9%, P = .02). The groups had similar rates of bleeding (1.2% vs. 1.4% P = 1.0) and thrombosis (3.7% vs. 4.6% P = 1.0). No patients in the brief stay group died within 100 days, compared with mortality of 1.8% (P = .6) in the prolonged stay group. CONCLUSION: Carefully selected patients receiving an autologous stem cell transplant for treatment of myeloma can be managed with a brief initial hospitalization and outpatient follow-up, with low morbidity and mortality. PMID- 26141215 TI - Retrospective efficacy and safety analyses of erlotinib, pemetrexed, and docetaxel in EGFR-mutation-negative patients with previously treated advanced non squamous non-small-cell lung cancer. AB - OBJECTIVE: Several guidelines recommend erlotinib, pemetrexed, or docetaxel for second-line chemotherapy in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The aim of this study was to retrospectively evaluate the efficacy of erlotinib, pemetrexed, and docetaxel in epidermal growth factor receptor (EGFR) mutation-negative patients with previously treated advanced non squamous NSCLC. MATERIALS AND METHODS: We analyzed the efficacy of these agents in patients with previously treated advanced non-squamous NSCLC who had EGFR wild type tumors, performance status (PS) of 0, 1, or 2 and received erlotinib, pemetrexed, or docetaxel between December 2007 and September 2011. Variability among patient backgrounds was evaluated using propensity scores to assess comparability. The efficacy of these agents was evaluated in patient subgroups with low variability. RESULTS: The propensity scores showed that the backgrounds of the groups that received second-line therapy with each agent had low variability and were adequate for comparison. Patients were divided into the PS0/1 and PS2 groups for analysis. The median progression-free survival (PFS) in patients treated with erlotinib was 2.8 months in the PS0/1 group, as compared with 1.0 month in the PS0/1/2 group and 0.90 months in the PS2 group. PFS in PS0/1 patients who received erlotinib was comparable to that in PS0/1 patients who received pemetrexed (2.5 months) or docetaxel (1.9 months). Overall survival (OS) in erlotinib-, pemetrexed-, and docetaxel-treated PS0/1 patients was 16.1, 7.4 and 10.0 months, respectively. The study had limited power to detect differences in PFS and OS because of the small sample size. CONCLUSIONS: Erlotinib appears to be a useful second-line option in PS0/1 patients with EGFR mutation-negative advanced non-squamous NSCLC given its mild adverse effects. The results should be carefully interpreted because of the small sample size, limited power, and retrospective nature of the study. PMID- 26141217 TI - Concurrence of EGFR amplification and sensitizing mutations indicate a better survival benefit from EGFR-TKI therapy in lung adenocarcinoma patients. AB - OBJECTIVES: Tumor heterogeneity, which causes different EGFR mutation abundance, is believed to be responsible for varied progression-free survival (PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment. Frequent EGFR amplification and its common affection in EGFR mutant allele promote the hypothesis that EGFR mutant abundance might be determined by EGFR copy number variation and therefore examination of EGFR amplification status in EGFR mutant patients could predict the efficacy of EGFR-TKI treatment. MATERIALS AND METHODS: In this study, 86 lung ADC patients, who harbored EGFR activating mutations and received EGFR-TKI treatment, were examined for EGFR amplification and expression by Dual-color Silver in situ Hybridization (DISH) and immunohistochemistry analysis, respectively. RESULTS AND CONCLUSION: Forty-one of 86 (47.7%) samples with EGFR activating mutations were identified with EGFR amplification. Patients with EGFR gene amplification had a significantly longer PFS than those without (16.3 vs. 9.1 months, p=0.004). The EGFR expression was then examined by immunohistochemistry analysis. Thirty-nine of 86 (45%) tumors had EGFR overexpression, which was significantly correlated with EGFR amplification (p=0.000). However, patients with EGFR overexpression exhibited no difference in PFS (14.1 vs. 13.3 months, p=0.797). In conclusion, EGFR amplification occurs frequently in lung ADC patients harboring EGFR activating mutations, and could serve as an indicator for better response from EGFR-TKI treatment. PMID- 26141216 TI - Tumoral CD10 expression correlates with high-grade histology and increases risk of recurrence in patients with stage I lung adenocarcinoma. AB - OBJECTIVE: CD10 (neutral endopeptidase) is expressed in various normal and tumor cells, and its biological function can be controlled through enzymatic activity and signaling pathways. We investigated whether CD10 expression predicted disease recurrence and whether it correlated with histologic subtypes of stage I lung adenocarcinoma. MATERIALS AND METHODS: We reviewed tumor slides of resected pathologic stage I lung adenocarcinomas (1995-2009). Tumors were classified according to the IASLC/ATS/ERS classification. CD10 immunohistochemistry was performed using tissue microarrays (n=915). We combined the intensity (0-3) and distribution scores (0-2) for CD10 to create a total score (0-5). Risk of recurrence was estimated using competing risks methods. RESULTS: In the training cohort (n=313), risk of recurrence of patients with high tumoral CD10 (score>1, n=57) was significantly higher (5-year cumulative incidence of recurrence [CIR], 37%) than in those with low CD10 (score<=1; n=256; 5-year CIR, 16%; P<0.001); this finding was confirmed in the validation cohort (n=602, P=0.036). High tumoral CD10 was associated with higher risk of recurrence in acinar (P=0.007) and papillary predominant tumors (P=0.022). High tumoral CD10 was most frequently identified in micropapillary predominant (41%) and solid predominant tumors (34%). On multivariate analysis of intermediate-grade tumors, high tumoral CD10 remained a significant independent risk factor of recurrence (hazard ratio, 1.88; P=0.025). CONCLUSION: In stage I lung adenocarcinoma, tumoral CD10 correlated with high-grade histology and was an independent predictor of recurrence in intermediate-grade tumors. PMID- 26141218 TI - IL1B gene polymorphisms, age and the risk of non-small cell lung cancer in a Chinese population. AB - BACKGROUND/OBJECTIVES: IL1B rs12621220G/A (-3893), rs1143623G/C (-1464), rs16944T/C (-511) and rs1143627C/T (-31) were previously reported to be associated with non-small cell lung cancer (NSCLC) and formed a specific haplotype (GGCT) which was associated with increased IL1B gene expression and increased risk of NSCLC in European populations. Only the two SNPs of rs16944T/C (-511) and rs1143627C/T (-31) have been studied in Chinese populations, and the results were conflicting. Thus we studied the association of the above four SNPs with NSCLC in a large Chinese population. METHODS: We genotyped IL1B SNPs in a case-control study with 889 lung cancer cases and 1005 controls using the SNPscan Genotyping system. We used logistic regression to determine the association between each SNP and NSCLC estimated by ORs and their 95% confidence intervals (CIs), controlling for Potential confounders as appropriate. RESULTS: In subjects over age 63, significant associations were detected between NSCLC and IL1B SNPs. For rs12621220G>A (-3893) and rs1143623G>C (-1464), heterozygous variants, when compared with ancestral genotype, were significantly associated with decreased risk of NSCLC, with adjusted odds ratio (aOR)=0.710 (0.516, 0.976), P=0.035 and aOR=0.643 (0.466, 0.886), P=0.007, respectively. For rs16944T>C (-511) and rs1143627C>T (-31), homozygous variants were significantly associated with increased risk of NSCLC, with aOR=1.482 (1.084, 2.025), P=0.014 and aOR=1.450 (1.055, 1.994), P=0.022, respectively. Inference of the haplotype structures showed that rs12621220G/A (-3893), rs1143623G/C (-1464), rs16944T/C (-511) and rs1143627C/T (-31) formed two risk haplotypes (GGCC and ACTT) with linkage disequilibrium in all subjects, and they have significantly different frequencies between cases and controls after the permutation tests for one hundred thousand times (P=0.0000E0). CONCLUSIONS: Our study provided evidence that IL1B SNPs might be implicated in the pathogenesis of NSCLC in the Chinese population. PMID- 26141219 TI - Icotinib might be effective for the treatment of leptomeningeal carcinomatosis in non-small cell lung cancer with sensitive EGFR mutations. AB - BACKGROUND: The incidence of leptomeningeal carcinomatosis (LMC) has increased in patients with metastatic non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of icotinib in the treatment of LMC. METHODS: Twenty-one NSCLC patients diagnosed with LMC and treated with icotinib were retrospectively reviewed. RESULTS: An exon 21 point mutation and an exon 19 deletion of EGFR were found in 10 and 11 patients, respectively. A standard dose of icotinib (125 mg/day, three times a day) was prescribed to 16 patients without previous icotinib therapy. A double dose of icotinib was prescribed to five patients who developed LMC during icotinib therapy with a standard dose. Eighteen of 20 patients showed improvement of dizziness and headache. Seventeen of 21 patients had an improved Eastern Cooperative Oncology Group performance status (ECOG PS) score after icotinib treatment. The median overall survival of the patients after the diagnosis of LMC was 10.1 months (95% confidence interval (CI): 8.4-12.0 months). Univariate analysis showed that the ECOG PS score, parenchymal brain metastasis, and previous icotinib administration were significantly associated with patient survival. Multivariate analysis also demonstrated that the ECOG PS score was an independent predictor for survival. CONCLUSION: Our results suggest that icotinib is effective for the treatment of LMC from NSCLC with an EGFR mutation, especially for patients with a good ECOG PS score. PMID- 26141220 TI - Impaired glutamatergic and GABAergic transmission by amitraz in primary hippocampal cells. AB - Amitraz is a formamidine pesticide that has been reported to be a neurotoxic compound that induces convulsions among other effects. Excitatory and inhibitory neurotransmission is mediated mainly by glutamate and GABA, respectively, so their alteration could be responsible for induction of seizures. In this regard, amitraz alpha2 adrenergic agonist action, which has been suggested as likely responsible for this effect, could alter these neurotransmitter systems and lead to seizure induction. Moreover, other amitraz mechanisms such as histamine H1 receptor inhibition could be involved. To confirm if amitraz disrupts glutamatergic/GABAergic transmission by these mechanisms, we evaluated, in primary hippocampal neurons, the effect of amitraz (0.01 MUM to 100 MUM) with or without the alpha2 adrenergic antagonist idazoxan (1 MUM) and/or the H1 receptor agonist n-methylhistaprodifen (30 MUM) co-treatment on 4-aminobutyrate aminotransferase, glutamate decarboxylase 65 (GAD 65), succinate-semialdehyde dehydrogenase and glutaminase gene expression and on glutamate and GABA levels after 24h treatment. We observed that amitraz disrupts glutaminase and GAD 65 gene expression, altering glutamatergic and GABAergic transmission. These effects were mediated partially by H1 and alpha2 receptors suggesting that other mechanisms could be involved. These data could help explain the mechanism by which amitraz induces seizures and provide a therapeutic strategy to protect against this effect in case of poisoning. PMID- 26141221 TI - Response to Pemberton and Hart "Consistent use of precise language decreases misunderstandings". PMID- 26141222 TI - A Framework for Effective Use of Hydroclimate Models in Climate-Change Adaptation Planning for Managed Habitats with Limited Hydrologic Response Data. AB - Climate-change adaptation planning for managed wetlands is challenging under uncertain futures when the impact of historic climate variability on wetland response is unquantified. We assessed vulnerability of Modoc National Wildlife Refuge (MNWR) through use of the Basin Characterization Model (BCM) landscape hydrology model, and six global climate models, representing projected wetter and drier conditions. We further developed a conceptual model that provides greater value for water managers by incorporating the BCM outputs into a conceptual framework that links modeled parameters to refuge management outcomes. This framework was used to identify landscape hydrology parameters that reflect refuge sensitivity to changes in (1) climatic water deficit (CWD) and recharge, and (2) the magnitude, timing, and frequency of water inputs. BCM outputs were developed for 1981-2100 to assess changes and forecast the probability of experiencing wet and dry water year types that have historically resulted in challenging conditions for refuge habitat management. We used a Yule's Q skill score to estimate the probability of modeled discharge that best represents historic water year types. CWD increased in all models across 72.3-100 % of the water supply basin by 2100. Earlier timing in discharge, greater cool season discharge, and lesser irrigation season water supply were predicted by most models. Under the worst-case scenario, moderately dry years increased from 10-20 to 40-60 % by 2100. MNWR could adapt by storing additional water during the cool season for later use and prioritizing irrigation of habitats during dry years. PMID- 26141223 TI - Divergent Impacts of Two Cattle Types on Vegetation in Coastal Meadows: Implications for Management. AB - The proportion of beef cattle in relation to the total number of cattle has increased in Europe, which has led to a higher contribution of beef cattle in the management of semi-natural grasslands. Changes in vegetation caused by this change in grazers are virtually unexplored so far. In the present study, the impacts of beef and dairy cattle on vegetation structure and composition were compared on Bothnian Bay coastal meadows. Vegetation parameters were measured in seven beef cattle, six dairy heifer pastures, and in six unmanaged meadows. Compared to unmanaged meadows, vegetation in grazed meadows was significantly lower in height and more frequently colonized by low-growth species. As expected, vegetation grazed by beef cattle was more open than that on dairy heifer pastures where litter cover and proportion of bare ground were in the same level as in the unmanaged meadows. However, the observed differences may have in part arisen from the higher cattle densities in coastal meadows grazed by beef cattle than by dairy heifers. The frequencies of different species groups and the species richness values of vegetation did not differ between the coastal meadows grazed by the two cattle types. One reason for this may be the relatively short management history of the studied pastures. The potential differences in grazing impacts of the two cattle types on vegetation structure can be utilized in the management of coastal meadows for species with divergent habitat requirements. PMID- 26141224 TI - Diagnostic performance and color overlay pattern in shear wave elastography (SWE) for palpable breast mass. AB - OBJECTIVE: The purpose of this study is to evaluate the diagnostic performance of SWE in palpable breast mass and to compare with color overlay pattern in SWE with conventional US and quantitative SWE for assessing palpable breast mass. METHODS: SWE and conventional breast US were performed in 133 women with 156 palpable breast lesions (81 benign, 75 malignant) between August 2013 to June 2014. Either pathology or periodic imaging surveillance more than 2 years was a reference standard. Existence of previous image was blinded to performing radiologists. US BI-RADS final assessment, qualitative and quantitative SWE measurements were evaluated. Diagnostic performances of grayscale US, SWE and US combined to SWE were calculated and compared. Correlation between pattern classification and quantitative SWE was evaluated. RESULTS: Both color overlay pattern and quantitative SWE improved the specificity of conventional US, from 81.48% to 96.30% (p=0.0005), without improvement in sensitivity. Color overlay pattern was significantly related to all quantitative SWE parameters and malignancy rate (p<0.0001.). The optimal cutoff of color overlay pattern was between 2 and 3. Emax with optimal cutoff at 45.1 kPa showed the highest Az value, sensitivity, specificity and accuracy among other quantitative SWE parameters (p<0.0001). Echogenic halo on grayscale US showed significant correlation with color overlay pattern and pathology (p<0.0001). CONCLUSIONS: In evaluation of palpable breast mass, conventional US combine to SWE improves specificity and reduces the number of biopsies that ultimately yield a benign result. Color overlay pattern classification is more quick and easy and may represent quantitative SWE measurements with similar diagnostic performances. PMID- 26141225 TI - Determination of Glucose Utilization Rates in Cultured Astrocytes and Neurons with [14C]deoxyglucose: Progress, Pitfalls, and Discovery of Intracellular Glucose Compartmentation. AB - 2-Deoxy-D-[14C]glucose ([14C]DG) is commonly used to determine local glucose utilization rates (CMRglc) in living brain and to estimate CMRglc in cultured brain cells as rates of [14C]DG phosphorylation. Phosphorylation rates of [14C]DG and its metabolizable fluorescent analog, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4 yl)amino)-2-deoxyglucose (2-NBDG), however, do not take into account differences in the kinetics of transport and metabolism of [14C]DG or 2-NBDG and glucose in neuronal and astrocytic cells in cultures or in single cells in brain tissue, and conclusions drawn from these data may, therefore, not be correct. As a first step toward the goal of quantitative determination of CMRglc in astrocytes and neurons in cultures, the steady-state intracellular-to-extracellular concentration ratios (distribution spaces) for glucose and [14C]DG were determined in cultured striatal neurons and astrocytes as functions of extracellular glucose concentration. Unexpectedly, the glucose distribution spaces rose during extreme hypoglycemia, exceeding 1.0 in astrocytes, whereas the [14C]DG distribution space fell at the lowest glucose levels. Calculated CMRglc was greatly overestimated in hypoglycemic and normoglycemic cells because the intracellular glucose concentrations were too high. Determination of the distribution space for [14C]glucose revealed compartmentation of intracellular glucose in astrocytes, and probably, also in neurons. A smaller metabolic pool is readily accessible to hexokinase and communicates with extracellular glucose, whereas the larger pool is sequestered from hexokinase activity. A new experimental approach using double labeled assays with DG and glucose is suggested to avoid the limitations imposed by glucose compartmentation on metabolic assays. PMID- 26141227 TI - The Shift in Outpatient Advanced Imaging From Private Offices to Hospital Facilities. AB - PURPOSE: To study recent outpatient imaging trends in private offices and hospital outpatient departments (HOPDs), to determine if shifting between the two has occurred. Concern is currently focused on whether reduced reimbursements and other factors might lead to a shift to higher-cost HOPDs. METHODS: The nationwide Medicare Physician/Supplier Procedure Summary Master Files for 2001 to 2013 were studied. All Current Procedural Terminology codes for MRI, echocardiography, nuclear medicine, ultrasound, and CT were selected, and procedure utilization rates per 1,000 Medicare beneficiaries were determined for each year. Medicare location codes identified the settings where the scans were performed. RESULTS: Total utilization rates, per 1,000 beneficiaries, of all these examination types in private offices, grew from 478 in 2001, to 874 in 2008 (+83%), and then declined to 503 in 2011 (-42%), primarily as a result of code bundling. No further bundling occurred in 2012 or 2013, but the decline continued in those years, to 462. In HOPDs, the total rate rose from 416 in 2001, to 523 in 2008 (+26%), followed by similar bundling-related declines, to 418 (-20%) in 2011. But in 2012 and 2013, in contrast to private office trends, the HOPD rate increased to 447. The ratio of private office to HOPD advanced imaging was 1.67 in 2008, declining to 1.03 in 2013. In addition, individual modality shifts away from offices and into HOPDs were quite apparent. CONCLUSIONS: In recent years, a shift has occurred in utilization of all advanced imaging modalities, from private offices to HOPDs. This change could portend a loss of access for patients and an increase in costs. PMID- 26141226 TI - The Use of Agmatine Provides the New Insight in an Experimental Model of Multiple Sclerosis. AB - The aim of the study is to investigate the hypothesis that agmatine (AGM) enhances blood brain barrier (BBB) compounds properties in experimental autoimmune encephalomyelitis (EAE), which is an established animal model for studying multiple sclerosis (MS). Wild-type (WT) and knockout (KO) CBA/H iNOS-/- mice, 3 months old (15 +/- 5 g) were used for EAE induction by myelin basic protein (MBP) dissolved in complete Freund's adjuvant (CFA). The animals were divided into control, CFA, EAE, EAE + AGM and AGM groups. After the development of full clinical remission, the animals were sacrificed and the immunohistochemical and biochemical examinations were performed in brain homogenates. We had noticed the increased expressions of occludin in WT and KO mice with EAE + AGM, compared to EAE groups in which these expressions were significantly decreased compared to the controls. The significant elevations of matrix metalloproteinases (MMPs)-MMP-3 and MMP-9 in WT and KO EAE animals were decreased during AGM treatment in both groups. AGM application post EAE in WT and KO mice caused decreased level of Iba-1 stain, compared to EAE groups. The obtained results suggest beneficial AGM effects in EAE on BBB components, which might be useful for novel therapeutic strategies in MS. PMID- 26141228 TI - Rural Mexican-Americans' perceptions of family health history, genetics, and disease risk: implications for disparities-focused research dissemination. AB - Disseminating the results of transdisciplinary health disparities research will increasingly involve discussing family health history and/or genetic information with study participants and their communities. Often, individuals' familiarity and comfort with these topics will be unclear. To inform the dissemination activities of a Center for Population Health and Health Disparities (CPHHD) studying multilevel determinants of breast cancer disparities in Latinas, we talked with Spanish-speaking Mexican-Americans from a rural agricultural community about family health history, genetics, and disease risk. We found that participants had limited genetic literacy but were familiar with some concepts related to family health history. Participants emphasized the role of individual behavior in shaping health and expressed a strong desire for health-related information. This included genetic information about future disease risk, which participants were previously unaware of but thought could be useful for disease prevention. These findings suggest that for research dissemination to facilitate health promotion, gaps in knowledge, particularly genetic knowledge, will need to be overcome. Outreach to underserved Latino communities should take advantage of this existing knowledge of family health history and strong desire for health information, but also take care to not overstate the significance of unreplicated or low-penetrance genetic associations. PMID- 26141229 TI - Rapid detection of beta-lactamases directly from positive blood cultures using a loop-mediated isothermal amplification (LAMP)-based assay. PMID- 26141230 TI - Vancomycin-associated nephrotoxicity: A meta-analysis of administration by continuous versus intermittent infusion. AB - Vancomycin is a glycopeptide antibiotic widely used in the management of meticillin-resistant Staphylococcus aureus (MRSA). Guidelines currently recommend vancomycin be administered by intermittent infusion, despite recent research suggesting that continuous infusion (CI) may be associated with lower rates of vancomycin-associated nephrotoxicity. In 2012, Cataldo et al. presented a meta analysis supporting the use of CI. Here we present an updated meta-analysis, inclusive of a recently published large-scale retrospective study. PubMed, EMBASE and Cochrane Reviews databases were searched using the keywords 'vancomycin' and 'continuous' or 'intermittent' or 'infusion' or 'discontinuous' or 'administration'. Seven studies were included in the final analysis. Using a random-effects model, a non-significant trend of reduced nephrotoxicity in those who received vancomycin by CI (risk ratio=0.799, 95% confidence interval 0.523 1.220; P=0.299) was identified. A large, randomised controlled trial is necessary to confirm these results. PMID- 26141231 TI - In vitro activity of solithromycin and its metabolites, CEM-214 and N-acetyl-CEM 101, against 100 clinical Ureaplasma spp. isolates compared with azithromycin. AB - There is a strong association between vaginal and/or amniotic fluid Ureaplasma spp. colonisation and risk of preterm birth. The novel fluoroketolide antibiotic solithromycin (CEM-101) is active against Ureaplasma spp. in vitro. Evidence from ex vivo and in vivo models suggests that, unlike most macrolide antibiotics, solithromycin readily crosses the placenta. Solithromycin metabolism varies according to species; in pregnant sheep, the bioactive metabolites CEM-214 and N acetyl-CEM-101 (NAc-CEM-101) have been shown to accumulate in the amniotic cavity following maternal solithromycin administration, potentially contributing to its antimicrobial effects. To determine the antimicrobial activity of these metabolites against Ureaplasma spp., the effects of solithromycin, CEM-214, NAc CEM-101 and the comparator azithromycin were tested on a collection of 100 clinical Ureaplasma spp. isolates from the UK and Australia using a modified 96 well broth microdilution method. MIC90 values observed for the combined cohort were: solithromycin, 0.125 mg/L; CEM-214, 0.5mg/L; NAc-CEM-101, 0.5mg/L; and azithromycin, 2mg/L. Solithromycin showed 34-fold greater activity against Ureaplasma spp. isolates than azithromycin, whilst CEM-214 and NAc-CEM-101 possessed ca. 22% and 17% of the activity of solithromycin, respectively, significantly greater than that of azithromycin. One bacterial isolate showed resistance to azithromycin (MIC=16 mg/L) but had a much lower MIC for solithromycin (MIC=0.25mg/L). In conclusion, the metabolites of solithromycin had reduced, but still potent, activity against 100 clinical Ureaplasma spp. isolates in vitro. This may be important in some instances such as pregnancy, however studies to determine levels of the metabolites in these settings are required. PMID- 26141232 TI - Interaction between mitsugumin 29 and TRPC3 participates in regulating Ca(2+) transients in skeletal muscle. AB - Mitsugumin 29 (MG29) is related to the fatigue and aging processes of skeletal muscle. To examine the roles of MG29 in conjunction with its binding protein, the canonical-type transient receptor potential cation channel 3 (TRPC3), in skeletal muscle, the binding region of MG29 to TRPC3 was studied along with the functional relevance of the binding in mouse primary skeletal myotubes using co immunoprecipitation assays and Ca(2+) imaging experiments. The N-terminus and the I-II loop of MG29 constitute the binding region for TRPC3. The myotubes that expressed the MG29 mutant missing the entire TRPC3-binding region showed a disrupted binding between endogenous MG29 and TRPC3 and a reduction in Ca(2+) transients in response to membrane depolarization without affecting ryanodine receptor 1 activity, the resting cytosolic Ca(2+) level, and the amount of releasable Ca(2+) from the sarcoplasmic reticulum. Among the proteins mediating Ca(2+) movements in skeletal muscle, TRPC4 expression was significantly decreased by the MG29 mutant. Therefore, MG29 could be a new factor for regulating Ca(2+) transients during skeletal muscle contraction possibly via a correlation with TRPC3 and TRPC4. PMID- 26141234 TI - Reduction of translation rate stabilizes circadian rhythm and reduces the magnitude of phase shift. AB - In the intracellular environment, the circadian oscillator is exposed to molecular noise. Nevertheless, cellular rhythms are robust and show almost constant period length for several weeks. To find which molecular processes modulate the stability, we examined the effects of a sublethal dose of inhibitors for processes in the molecular clock. Inhibition of PER1/2 phosphorylation by CKIepsilon/delta led to reduced amplitude and enhancement of damping, suggesting that inhibition of this process destabilized oscillation. In contrast, moderate inhibition of translation led to stabilization of the circadian oscillation. Moreover, inhibition of translation also reduced magnitude of phase shift. These results suggest that some specific molecular processes are crucial for stabilizing the circadian rhythm, and that the molecular clock may be stabilized by optimizing parameters of some crucial processes in the primary negative feedback loop. Moreover, our findings also suggested that rhythm stability is closely associated with phase stability against stimuli. PMID- 26141233 TI - IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer. AB - IL-15 has pivotal roles in the control of CD8(+) memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-gamma production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-gamma in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-gamma production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2 stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-gamma production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-gamma production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy. PMID- 26141235 TI - Habitual exercise training acts as a physiological stimulator for constant activation of lipolytic enzymes in rat primary white adipocytes. AB - It is widely accepted that lipolysis in adipocytes are regulated through the enzymatic activation of both hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) via their phosphorylation events. Accumulated evidence shows that habitual exercise training (HE) enhances the lipolytic response in primary white adipocytes with changes in the subcellular localization of lipolytic molecules. However, no study has focused on the effect that HE exerts on the phosphorylation of both HSL and ATGL in primary white adipocytes. It has been shown that the translocation of HSL from the cytosol to lipid droplet surfaces requires its phosphorylation at Ser-563. In primary white adipocytes obtained from HE rats, the level of HSL and ATGL proteins was higher than that in primary white adipocytes obtained from sedentary control (SC) rats. In HE rats, the level of phosphorylated ATGL and HSL was also significantly elevated compared with that in SC rats. These differences were confirmed by Phos-tag SDS-PAGE, a technique used to measure the amount of total phosphorylated proteins. Our results suggest that HE can consistently increase the activity of both lipases, thereby enhancing the lipolysis in white fat cells. Thus, HE helps in the prevention and treatment of obesity-related diseases by enhancing the lipolytic capacity. PMID- 26141236 TI - Left ventricular non compaction with aortic valve anomalies: A recurrent feature of 22q11.2 distal deletion syndrome. PMID- 26141237 TI - Virulence and antimicrobial resistance factors of Enterococcusspp. isolated from fecal samples from piggery farms in Eastern Cape, South Africa. AB - BACKGROUND: Enterococci have emerged as an important opportunistic pathogen causing life-threatening infections in hospitals. The emergence of this pathogen is associated with a remarkable capacity to accumulate resistance to antimicrobials and multidrug-resistance particularly to vancomycin, erythromycin and streptomycin have become a major cause of concern for the infectious diseases community. In this paper, we report the prevalence of Enterococcus in respect to species distribution, their virulence and antibiogram profiles. METHODS: Four hundred fecal samples were collected from two piggery farms in the Eastern Cape Province of South Africa. Enterococcus species were isolated and confirmed with generic specific primers targeting the tuf gene (encoding elongation factor). The confirmed isolates were speciated with enterococci species specific primers that aimed at delineating them into six species that are commonly associated with infections in humans. Antibiotic susceptibility testing was performed by disc diffusion method. Six virulence genes and antimicrobial resistance profiles of the isolates were evaluated molecularly. RESULTS: Molecular identification of the presumptive isolates confirmed 320 isolates as Enterococcus spp. Attempt at speciation of the isolates with primers specific for E. faecalis, E. durans, E. casseliflavus, E. hirae and E. faecium delineated them as follows: E. faecalis (12.5 %), E. hirae (31.25 %), E. durans (18.75 %) and E. faecium (37.5 %) while E. casseliflavus was not detected. All the isolates were resistant to vancomycin, streptomycin and cloxacillin, and to at least two different classes of antibiotics, with 300 (93.8 %) isolates being resistant to five or more antibiotics. Also, three out of the six virulence genes were detected in majority of the isolates and they are Adhesion of collagen in E. faecalis (ace) (96.88 %), gelatinase (gelE) (93.13 %) and surface protein (esp) (67.8 %). CONCLUSION: There was high prevalence of multi-resistant vancomycin Enterococcus spp. (VREs) in the fecal samples of pigs in the farms studied, and this poses health implications as vancomycin is an important drug in human medicine. Further studies are needed to determine the spread of vancomycin resistance among bacteria of human origin in the communities. PMID- 26141238 TI - Reduced intrasubject variability with reinforcement in boys, but not girls, with ADHD: Associations with prefrontal anatomy. AB - This study examined the impact of motivational contingencies (reinforcement and punishment) on go/no-go (GNG) task performance in girls and boys with ADHD relative to typically developing (TD) children and associations with prefrontal anatomy. Children ages 8-12 with ADHD (n=107, 36 girls) and TD controls (n=95, 34 girls) completed a standard and a motivational GNG task and associations with prefrontal cortex (PFC) surface area were examined. Intrasubject variability (ISV) was lower during the motivational compared to the standard GNG among TD girls and boys, and boys with ADHD, but not among girls with ADHD. A greater reduction in ISV was associated with greater PFC surface area among children with ADHD. This novel demonstration of improvement in ISV with motivational contingencies for boys, but not girls, with ADHD and associations with PFC anatomy informs our understanding of sex differences and motivational factors contributing to ISV in children with ADHD. PMID- 26141239 TI - Improved structural method for T-cell cross-reactivity prediction. AB - Cytotoxic T-lymphocytes (CTLs) are the key players of adaptive cellular immunity, being able to identify and eliminate infected cells through the interaction with peptide-loaded major histocompatibility complexes class I (pMHC-I). Despite the high specificity of this interaction, a given lymphocyte is actually able to recognize more than just one pMHC-I complex, a phenomenon referred as cross reactivity. In the present work we describe the use of pMHC-I structural features as input for multivariate statistical methods, to perform standardized structure based predictions of cross-reactivity among viral epitopes. Our improved approach was able to successfully identify cross-reactive targets among 28 naturally occurring hepatitis C virus (HCV) variants and among eight epitopes from the four dengue virus serotypes. In both cases, our results were supported by multiscale bootstrap resampling and by data from previously published in vitro experiments. The combined use of data from charges and accessible surface area (ASA) of selected residues over the pMHC-I surface provided a powerful way of assessing the structural features involved in triggering cross-reactive responses. Moreover, the use of an R package (pvclust) for assessing the uncertainty in the hierarchical cluster analysis provided a statistical support for the interpretation of results. Taken together, these methods can be applied to vaccine design, both for the selection of candidates capable of inducing immunity against different targets, or to identify epitopes that could trigger undesired immunological responses. PMID- 26141240 TI - Endogenous ligands of natural killer T cells are alpha-linked glycosylceramides. AB - The nature of the endogenous ligands for natural killer T (NKT) cells has been debated for more than a decade. Because the mammalian glycosylceramide synthases are invertases, it is believed that in mammals all glycosylceramides are beta anomers. However, the possibility that an alternative enzymatic pathway, an unfaithful enzyme, or unique physico-chemical environments could allow the production of small quantities of alpha anomers should be entertained. Classic biochemical and chemical analysis approaches are not well suited for this challenge as they lack sensitivity. Using a combination of biological assays and new technological approaches, we have unequivocally demonstrated that alpha glycosylceramides were constitutively produced by mammalian immune cells, loaded onto CD1d and presented to NKT cells both in the thymus and in the periphery. Their amount is controlled tightly by catabolic enzymes, and can be altered in vitro and in vivo to modify NKT cell behavior. PMID- 26141241 TI - Blood miRNAs as sensitive and specific biological indicators of environmental and occupational exposure to volatile organic compound (VOC). AB - To date, there is still shortage of highly sensitive and specific minimally invasive biomarkers for assessment of environmental toxicants exposure. Because of the significance of microRNA (miRNA) in various diseases, circulating miRNAs in blood may be unique biomarkers for minimally invasive prediction of toxicants exposure. We identified and validated characteristic miRNA expression profiles of human whole blood in workers exposed to volatile organic compounds (VOCs) and compared the usefulness of miRNA indicator of VOCs with the effectiveness of the already used urinary biomarkers of occupational exposure. Using a microarray based approach we screened and detected deregulated miRNAs in their expression in workers exposed to VOCs (toluene [TOL], xylene [XYL] and ethylbenzene [EBZ]). Total 169 workers from four dockyards were enrolled in current study, and 50 subjects of them were used for miRNA microarray analysis. We identified 467 miRNAs for TOL, 211 miRNAs for XYL, and 695 miRNAs for XYL as characteristic discernible exposure indicator, which could discerned each VOC from the control group with higher accuracy, sensitivity, and specificity than urinary biomarkers. Current observations from this study point out that the altered levels of circulating miRNAs can be a reliable novel, minimally invasive biological indicator of occupational exposure to VOCs. PMID- 26141242 TI - Associations between dietary factors and urinary concentrations of organophosphate and pyrethroid metabolites in a Canadian general population. AB - OBJECTIVES: Few studies to date have characterized the relationships between diet and urinary concentrations of pesticides. In the current study, associations between dietary factors and urinary concentrations of organophosphate and pyrethroid metabolites were examined in a Canadian general population using data from the Canadian Health Measures Survey (CHMS). METHODS: In the CHMS, urinary concentrations of dialkylphosphate (DAP) and pyrethroid metabolites were measured in 5604 participants aged 6-79 years. Associations between dietary factors and total concentrations of DAP (SigmaDAP) and pyrethroid metabolites (SigmaPYR) were examined. RESULTS: Over 90% of participants had at least one type of DAP and 99.8% had pyrethroid metabolites detectable in urine samples. After adjusting for age, sex, race/ethnicity, immigrant status and body mass index, SigmaDAP among participants with high (3rd tertile) fruit consumption was 1.43 (95% CI: 1.26 1.61) times the concentration among those with low (1st tertile) consumption. SigmaDAP was also positively associated with vegetable consumption, for those with high consumption SigmaDAP being 1.33 times (95% CI: 1.16-1.52) the concentration for those with low consumption. SigmaPYR among participants with high vegetable consumption was 1.42 (95% CI: 1.23-1.66) times the concentration among those with low vegetable consumption. SigmaPYR was also positively associated with pulses/nuts consumption (p-values<0.01) and household use of chemicals to control head lice or pet flea (p=0.002). CONCLUSIONS: Positive associations between dietary factors and urinary concentrations of organophosphate and pyrethroid metabolites suggest greater regulation of pesticide use on food products may help to reduce pesticide exposures and associated health risks among the general population. PMID- 26141243 TI - Recovery of renal function after glucocorticoid therapy for IgG4-related kidney disease with renal dysfunction. AB - BACKGROUND: Although renal dysfunction in IgG4-related kidney disease (IgG4-RKD) shows rapid resolution with glucocorticoid therapy, little is known about the appropriate initial glucocorticoid dose for induction therapy or long-term renal outcome. METHODS: We retrospectively examined the differences in recovery of renal function according to the dose of glucocorticoid used for induction therapy and the long-term renal outcome in 43 patients with definite IgG4-RKD (mostly IgG4-tubulointerstitial nephritis), in whom the estimated glomerular filtration rate (eGFR) before glucocorticoid therapy was <60 ml/min. RESULTS: Most patients were treated with glucocorticoid alone and had been maintained on glucocorticoid. The initial dose of prednisolone employed was <=0.6 mg/kg/day (mean 0.47) in 27 patients (group L), and >0.6 mg/kg/day (mean 0.81) in 16 patients (group H). In both groups, the pretreatment eGFR was significantly improved at 1 month after the start of glucocorticoid therapy and the degree of improvement showed no significant inter-group difference. Relapse of IgG4-RKD occurred in 16.7% of the group L patients and 13.3% of the group H patients (p = 0.78). Among 29 patients who were followed up for over 36 months (mean 74 months) and had been maintained on glucocorticoid, none showed progression to end-stage renal disease and there was no significant difference between eGFR at 1 month after treatment and eGFR at the last review. CONCLUSION: In glucocorticoid monotherapy for IgG4-RKD, a moderate dose is sufficient for induction, and recovery of renal function can be maintained for a long period on low-dose maintenance, although relapse can occur even in patients receiving maintenance therapy. PMID- 26141244 TI - Identification of physical and psychosocial problems associated with diabetic nephropathy using the International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus. AB - BACKGROUND: We previously demonstrated validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus (ICF-CS for DM) in patients with diabetic nephropathy (DMN). The objective of the present study was to identify differences in experience of physical and psychosocial problems between DMN patients with and without hemodialysis (HD), and diabetes patients without nephropathy using the ICF-CS for DM. METHODS: A total of 302 diabetes outpatients (men, 68 %; mean age, 62 years) were interviewed using four components of the ICF-CS for DM including "Body functions", "Body structures", "Activities and participation", and "Environmental factors". RESULTS: The mean number of categories in which difficulty was experienced in the four components was significantly greater in DMN patients with HD followed by DMN patients without HD, and diabetes patients without nephropathy (23.9 vs. 18.0 vs. 13.1, respectively). Multivariate logistic regression models revealed that, compared with diabetes patients without nephropathy, diabetes patients with nephropathy were more likely to have difficulty with physical problems and social activities and participation. Among DMN patients, dialysis patients were found to have larger numbers of problems, and face difficulty with employment status after adjusting for sex, age, type, and duration of diabetes. CONCLUSION: The results of this study using the ICF-CS for DM identified the areas for improvement among physical and psychosocial problems in DMN patients with and without HD in contrast to diabetes patients without nephropathy. PMID- 26141245 TI - [Algorithms, machine intelligence, big data : general considerations]. AB - We are experiencing astonishing developments in the areas of big data and artificial intelligence. They follow a pattern that we have now been observing for decades: according to Moore's Law,the performance and efficiency in the area of elementary arithmetic operations increases a thousand-fold every 20 years. Although we have not achieved the status where in the singular sense machines have become as "intelligent" as people, machines are becoming increasingly better. The Internet of Things has again helped to massively increase the efficiency of machines. Big data and suitable analytics do the same. If we let these processes simply continue, our civilization may be endangerd in many instances. If the "containment" of these processes succeeds in the context of a reasonable political global governance, a worldwide eco-social market economy, andan economy of green and inclusive markets, many desirable developments that are advantageous for our future may result. Then, at some point in time, the constant need for more and faster innovation may even stop. However, this is anything but certain. We are facing huge challenges. PMID- 26141246 TI - [Fruit and vegetable consumption by children and adolescents in Germany: Results of KiGGS wave 1]. AB - BACKGROUND: A high fruit and vegetable intake contributes to a healthy diet, which is very important for the development of children and adolescents. OBJECTIVES: With data from the first follow-up survey of the Child and Adolescent Health Surveys (KiGGS wave 1) the fruit and vegetable intake and its association with determinants are analyzed. METHODS: Via telephone interviews the average numbers of portions of fruits and vegetables consumed by 9,950 girls and boys aged 3-17 years were assessed. In addition, the proportion of persons achieving five portions of fruits and vegetables per day was calculated. The number of portions was analyzed in association with social status, parent's educational level, media consumption, and other determinants via multiple linear regression models. RESULTS: Only 12.2 % of girls and 9.4 % of boys consume the recommended five portions of fruits and vegetables per day. 38.6 % of girls and 33.5 % of boys consume at least three portions per day. On average, girls consume 2.7 and boys 2.4 portions of fruits and vegetables per day. Younger participants consume significantly more portions of fruits than older participants. The percentage of persons consuming five or at least three portions per day increases significantly with higher socioeconomic status, higher parent's educational level, and lower media consumption. Furthermore, children who conduct sport outside of school, those who are physically active every day, and boys living in central Germany consume significantly more portions of fruit and vegetables. CONCLUSION: Most children and adolescents do not consume enough fruits and particularly vegetables. The consumption differs considerably according to socio-demographic background and lifestyle factors, which should be considered in promotional campaigns. PMID- 26141248 TI - Editorial Introduction: New Journal Features. PMID- 26141247 TI - Accelerometer determined sedentary behavior and dietary quality among US adults. AB - OBJECTIVE: Scant evidence exists pertaining to objectively measured sedentary time and dietary quality among adults. Therefore, we examined the relationships between sedentary time, physical activity, and dietary quality. METHODS: Cross sectional analyses of a 4,910 US adults from two cycles (2003-2006) of the National Health and Nutrition Examination Survey. The primary independent variables were sedentary time and physical activity (continuous and categorical), while the outcomes were overall dietary quality (Healthy Eating Index (HEI) 2010), fruit and vegetable scores, and empty caloric intake (kcal). RESULTS: Multivariable analyses revealed that a 1min increase in daily sedentary behavior was associated with a 0.2kcal decrease in empty calories (-0.18, 95% CI=-0.34, 0.03); however, sedentary time was not significantly related to overall dietary quality (HEI) and fruit and vegetable intake. In comparison, a 1min increase in daily moderate-to-vigorous intensity physical activity was related to a 0.1 higher HEI score (0.08, 95% CI=0.04, 0.11), a 0.01 higher fruit score (0.01, 95% CI=0.01, 0.02), and conversely a 1.3kcal decrease in empty calories (-1.35, 95% CI=-2.01, -0.69). In addition, meeting physical activity guidelines was associated with a 2.8 point higher HEI score (2.82, 95% CI=1.40, 4.25), a 0.5 point higher fruit score (0.51, 95% CI=0.31-0.71), and 37.4 fewer empty calories (-37.43, 95% CI=-64.86, -9.10). CONCLUSIONS: Physical activity is significantly related to better overall dietary quality, while sedentary behavior is not. Findings suggest the need to promote physical activity and encourage adherence to dietary guidelines jointly, whereas sedentary behavior and overall dietary quality might need to be targeted independently. PMID- 26141249 TI - Development of the Critical Elements of Genetic Evaluation and Genetic Counseling for Genetic Professionals and Perinatologists in Washington State. AB - We present a method for the development of consensus documents describing the components of genetic evaluation and genetic counseling for various diagnoses. These documents were developed to encourage consistency among genetic professionals in Washington State. Other possible uses of these documents are to provide information regarding genetic evaluations for health care practitioners and payers, and to assist in quality assurance and genetic training programs. A working group of six genetic professionals developed two templates for the "critical elements of genetic evaluation and genetic counseling," for clinical (nonprenatal) and prenatal patients. The working group then completed prototype templates for several specific genetic disorders. The templates and prototypes were sent to interested genetic professionals and perinatologists who submitted a total of 76 draft "critical elements" (CE's) to the working group. At two statewide meetings, participating practitioners modified and unanimously approved the CE templates, then unanimously approved the 21 draft CEs that had been finalized in small group discussions. Approved CE's were distributed to genetic professionals and perinatologists within the state. PMID- 26141250 TI - Experiential Family Therapy: An Innovative Approach to the Resolution of Family Conflict in Genetic Counseling. AB - Experiential family therapy is an intuitive approach that utilizes active, multisensory techniques. These techniques, such as role plays and drawings, increase the family's expression of affect and uncover new information. Increased affect and uncovered information stimulate change and growth in the family system. Experiential techniques are especially useful when more traditional, verbal-based communication is not effective. In this article, I will present a pediatric case in which the patient, a 7-year-old boy diagnosed with autism, was referred to the genetics clinic to rule out the presence of an associated genetic disorder. I will then describe a hypothetical second counseling session with the same family and suggest how three experiential family therapy techniques: family drawing, "empty chair" technique, and continuums might be used in the session to help resolve a marital conflict between the patient's parents. PMID- 26141252 TI - Genetic Library. PMID- 26141251 TI - Genetic Counseling for Confined Placental Mosaicism: A Case Report. AB - New technologies can lead to unforeseen discoveries which in turn can lead to diagnostic and counseling dilemmas. A case which involved confined placental mosaicism for trisomy 16 is presented to illustrate such a situation. While interpreting data and explaining a newly described phenomenon created uncertainties for the genetic counseling team, the patient and her husband were primarily dealing with grief surrounding the loss of a wanted pregnancy. It is important to recognize that the counseling issues may be different for the professionals and the families. Genetic counselors must be cognizant of their own reactions and those of their clients and be prepared to use all of their counseling skills to address these varying needs. PMID- 26141253 TI - Evolution of nanoscale clusters in gamma' precipitates of a Ni-Al-Ti model alloy. AB - The evolution of phase separation and ordering processes determines the structure and properties of Ni-based superalloys. Here we use atom probe tomography to clarify the origin of gamma particles occurring in ordered (L12) gamma' precipitates in a Ni86.1Al8.5Ti5.4 alloy. Particularly, we elucidate the evolution from nanoscaled Ni-rich heterogeneities (Ni-rich clusters) to gamma spheres and then gamma plates inside gamma' precipitates from the compositional and the thermodynamic point of view. We find that Ni supersaturation of gamma' precipitates is relieved by formation of Ni-rich clusters, which results in an energetically more favorable state. Subsequently, coalescence introduces necking between the Ni-rich clusters and leads to the formation of gamma particles. Our results demonstrate that phase separation of gamma' precipitates is characterized by different stages with various governing driving forces. PMID- 26141254 TI - Determination of lymph flow in murine oral mucosa using depot clearance of near infrared-labeled albumin. AB - The lymphatic vessels are playing an important role in inflammation since they return extravasated fluid, proteins, and cells back into the circulation and regulate immune cell trafficking. The oral mucosa, including gingiva, is well supplied with lymphatic vessels and is frequently challenged with inflammatory insults. Lymphatic vessels in gingiva protect against periodontal disease development, but quantification of lymph flow in this area has so far never been performed, due to lack of reliable methods. Mice of FVB strain (n=17) were anesthetized with isoflurane and placed on a jaw retraction board allowing the mouth to be kept open and stable. Albumin conjugated with Alexa680-fluorochrome (with or without LPS from Porphyromonas gingivalis) was injected superficially in oral mucosa mesio-buccal to the left first molar in each mouse. 60 min post injection the mouse was transferred to an OptixMX3 optical imager where the total fluorescence was measured in the posterior facial area. The measurements continued further every 60 min for 7h for each mouse. The mice were awake and active between measurements. The in vivo washout of Alexa680-albumin was calculated using the natural logarithm of the relative values creating a negative slope for each mouse. Statistical analysis of variance was performed. The injection and distribution site for tracer was verified with India ink and shown to be in the interstitium below the oral mucosal epithelium, in an area well supplied with initial lymphatic vessels. Washout of the tracer Alexa680-albumin was log-linear, and the basal lymph flow calculated from depot clearance averaged -0.28 +/- 0.08%/min (n=8). The clearance was significantly faster (-0.30 +/- 0.08%/min, n=9) in acutely inflamed oral mucosa (p=0.0326). We developed a method that can successfully quantify the lymph flow in oral mucosa in steady state conditions and under acute perturbation. By use of this method, new information about the lymphatic function in oral mucosa during physiological and pathological conditions can be achieved. PMID- 26141255 TI - Seasonal changes in the incidence of Escherichia coli bloodstream infection: variation with region and place of onset. AB - Previous research has shown that Escherichia coli infection rates peak in the summer; however, to date there has been no investigation as to whether this is seen in both hospital and community-onset cases, and how this differs across regions. We investigated and quantified E. coli bloodstream infection (BSI) seasonality. A generalized additive Poisson model was fitted to mandatory E. coli BSI surveillance data reported in England. There was no impact of seasonality in hospital-onset cases; however, for the community-onset cases, there was statistically significant seasonal variation over time nationally. When examined regionally, seasonality was significant in the North of England only. This variation resulted in an absolute increase of 0.06 (95% CI 0.02-0.1) cases above the mean (3.25) in each hospital trust for each week of the peak summer season, and a decrease of (-) 0.07 (95% CI -0.1 to -0.03) in the autumn. We estimate that fewer than one hospital bed-day per week per hospital is lost because of seasonal increases during the summer. Our findings highlight the need to understand the distinct community and hospital dynamics of E. coli BSI, and to explore the regional differences driving the variation in incidence, in order to design and implement effective control measures. PMID- 26141256 TI - Different possible surgical managements of caustic ingestion: diagnostic laparoscopy for Zargar's grade 3a lesions and a new technique of "Duodenal Damage Control" with "4-tubes ostomy" and duodenal wash-out as an option for extensive 3b lesions in unstable patients. AB - In the present study, we have described two possible approaches in the management of caustic injuries. Diagnostic emergency laparoscopy can be used for exploration in case of stable patients with Zargar's 3a gastric lesions and equivocal peritoneal signs. On the other hand, in case of patients with Zargar's 3b gastric lesions with perforation, diffuse peritonitis and hemodynamic instability, a new possible technique is described as an option to be used in such extensive caustic injuries: duodenal damage control with "4-tubes ostomy" for duodenal and jejunal wash-out of the caustic agent. The aim of this simple technique is to wash-out the caustic agent from the duodenum when the duodenum and Treitz are not yet gangrenous/perforated, as well as to avoid duodenal primary closure and jejuno jejunal anastomosis over damaged tissues. PMID- 26141257 TI - Low vitamin D status is associated with more depressive symptoms in Dutch older adults. AB - PURPOSE: The existence of vitamin D receptors in the brain points to a possible role of vitamin D in brain function. We examined the association of vitamin D status and vitamin D-related genetic make-up with depressive symptoms amongst 2839 Dutch older adults aged >=65 years. METHODS: 25-Hydroxyvitamin D (25(OH)D) was measured, and five 'vitamin D-related genes' were selected. Depressive symptoms were measured with the 15-point Geriatric Depression Scale. Results were expressed as the relative risk of the score of depressive symptoms by quartiles of 25(OH)D concentration or number of affected alleles, using the lowest quartile or minor allele group as reference. RESULTS: A clear cross-sectional and prospective association between serum 25(OH)D and depressive symptom score was observed. Fully adjusted models indicated a 22 % (RR 0.78, 95 % CI 0.68-0.89), 21 % (RR 0.79, 95 % CI 0.68-0.90), and 18 % (RR 0.82, 95 % CI 0.71-0.95) lower score of depressive symptoms in people in the second, third, and fourth 25(OH)D quartiles, when compared to people in the first quartile (P for trend <0.0001). After 2 years of daily 15 ug vitamin D supplementation, similar associations were observed. 25(OH)D concentrations did not significantly interact with the selected genes. CONCLUSION: Low serum 25(OH)D was associated with higher depressive symptom scores. No interactions between 25(OH)D concentrations and vitamin D genetic make-up were observed. In view of the probability of reverse causation, we propose that the association should be further examined in prospective studies as well as in randomized controlled trials. PMID- 26141258 TI - Effects of triacylglycerol structure and solid fat content on fasting responses of mice. AB - PURPOSE: Fat randomization and interesterification change triacylglycerol (TAG) structure and its solid fat content profile. It has not been thoroughly investigated whether these changes affect lipid metabolism. METHODS: Two experiments were conducted to investigate the effects of TAG structure and solid fat content on feed intake, body weight change, and serum metabolite concentrations in mice. An experiment used two fats rich in 1,2-dipalmitoyl-3 oleoylglycerol (PPO) and 1,3-dipalmitoyl-2-oleoylglycerol (POP) as comparative pair of fats to assess the effect of TAG structure since PPO and POP have the same fatty acid composition and solid fat content at 37 degrees C. Another experiment used a fat rich in 1-palmitoyl-2,3-dioleoylglycerol (POO) with solid fat content of zero at 37 degrees C and a mixture of fats that had the same general fatty acid composition and palmitic acid positional distribution, but with solid fat content of 22 % at 37 degrees C. This pair of fats was used to examine the effect of solid fat content on blood lipid profile. RESULTS: After 6 week feeding, the pair of fats with different solid fat contents did not significantly affect the concentrations of total serum cholesterol, HDL cholesterol, TAG, non-esterified fatty acid (NEFA), or blood glucose. However, the PPO fat significantly reduced feed intake, body weight, and serum glucose concentration as compared to POP. CONCLUSION: These results suggest that the presence of solid fat at the level examined does not affect lipid metabolism and lipemia, but PPO diet significantly affects NEFA and glucose concentrations. Palmitic acid at the sn-2 position of the TAG may have significant effect on appetite, which may be mediated via the gut receptors. PMID- 26141259 TI - Sepsis-induced acute kidney injury in patients with cirrhosis. AB - Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment. PMID- 26141260 TI - Dysphagia in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus. AB - BACKGROUND: Head and neck cancer (HNC) and its therapy are associated with acute and late swallowing dysfunction. Consensus guidelines regarding evaluation and management are lacking. To address this gap, a multidisciplinary team of experts (oncologists, practitioners, deglutologists, etc.) met in Milan 17-18 February 2013 with the aim of reaching a consensus on the management of swallowing difficulties in HNC patients treated with radiotherapy with or without systemic therapies (such as chemotherapy and targeted agents). The consensus was focused particularly on those statements with limited evidence. The results of the literature review and the statements that obtained a consensus are reported and discussed in this paper. MATERIALS AND METHODS: The Delphi Appropriateness Method was used for this consensus. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. RESULTS: This paper contains 6 clusters of statements about the management of swallowing problems in radio-treated HNC patients and a review of the recent literature on these topics. CONCLUSIONS: Dysphagia assessment and its management are difficult and require a multi-team cooperation (ENT specialists, radiation and medical oncologists, deglutologists, etc.). PMID- 26141261 TI - A neuropathological study of cerebrovascular abnormalities in a signal transducer and activator of transcription 3-deficient patient. PMID- 26141262 TI - Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract. AB - BACKGROUND: Allergen immunotherapy is an effective treatment of allergic rhinoconjunctivitis. Clinical efficacy is associated with improvement of basophil sensitivity and an increase in allergen-specific immunoglobulin concentration. OBJECTIVE: We sought to determine whether changes in allergen component-specific serum IgE and IgG4 levels during the updosing phase of subcutaneous immunotherapy (SCIT) are biomarkers of the immunologic changes that can lead to treatment efficacy. METHODS: Twenty-four subjects with grass pollen-induced allergic rhinoconjunctivitis were randomized 3:1 to receive SCIT (Alutard SQ) or to an open control group. IgE and IgG4 concentrations were determined for the major allergens Phl p 1 or Phl p 5 by using ImmunoCAP and for 8 grass pollen molecules by using Immuno Solid-phase Allergy Chip (ISAC) before treatment and after updosing. RESULTS: Levels of specific IgE against the dominant major allergens Phl p 1 and Phl p 5 increased from a mean of 23.0 to 48.8 kU/L (P = .01, n = 18) during the updosing phase in ImmunoCAP measurements but decreased from a median of 4.6 ISAC specific units (ISU) to 2.14 ISU (P < .0001, n = 102) when measured by using ISAC against 8 grass allergen components. The updosing phase induced a specific IgG4 level increase from a median of 0 ISU before treatment to 0.83 ISU after 12 weeks (P < .0001, n = 102) but only for allergen molecules to which pretreatment-specific IgE antibodies were detected (Spearman sigma = 0.72, P < .0001, n = 102). CONCLUSION: Pretreatment allergen component-specific IgE appears to determine the induction of IgG4 in the updosing phase. Induced IgG4 seems to suppress IgE levels on ISAC, resulting in a marked decrease in ISAC-measured specific IgE levels after updosing of SCIT. Thus this decrease in ISAC IgE levels can be used to monitor the blocking effect of allergen-specific immunotherapy induced non-IgE antibodies. PMID- 26141263 TI - Preventive effect of nasal filters on allergic rhinitis: A randomized, double blind, placebo-controlled crossover park study. AB - BACKGROUND: A recently reported small, out-of-season environmental exposure unit study found nasal filters to be efficacious in preventing seasonal allergic rhinitis (AR). However, nasal filters still need to show efficacy in a natural setting in a regular pollen season. OBJECTIVE: We sought to evaluate the efficacy of nasal filters (Rhinix; Rhinix ApS, Aarhus, Denmark) for the prevention of symptoms related to seasonal AR. METHODS: The trial was a single-center, randomized (1:1), double-blind, placebo-controlled crossover clinical trial (NCT02108574) conducted over 2 days in the main grass pollen season in June 2014 in Aarhus, Denmark, on 65 adults with proven grass allergy. A total nasal symptom score (TNSS) consisting of blocked nose, runny nose, nasal itching, and sneezing was used to evaluate symptoms. The difference in daily? TNSS (the sum of 13 ratings) was the primary outcome measure. The difference in maximum TNSS (highest score, 13 ratings) was also evaluated. RESULTS: The nasal filters significantly reduced daily? TNSSs (P = .03) and maximum TNSSs (P = .03) compared with placebo. Median relative reductions were 40% for daily? TNSSs (P = .02), 43% for maximum TNSSs (P = .004), 83% for daily? sneezing (P = .001), 75% for daily? watery eyes (P = .02), and 53% for daily? runny nose (P = .005) when compared with placebo. The nasal filters were well tolerated, and no serious adverse events were recorded. CONCLUSION: Statistically significant and clinically relevant reductions were achieved for the primary outcome measure of daily? TNSS, for maximum TNSS and for a subset of individual symptoms. The results support the preventive role of nasal filters for managing seasonal AR. PMID- 26141264 TI - [(18)F]flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer's disease: specific detection of advanced phases of amyloid beta pathology. AB - BACKGROUND: Amyloid positron emission tomography (PET) has become an important tool to identify amyloid-beta (Abeta) pathology in Alzheimer's disease (AD) patients. Here, we determined the diagnostic value of the amyloid PET tracer [(18)F]flutemetamol in relation to Abeta pathology at autopsy. METHODS: [(18)F]flutemetamol PET was carried out in a cohort of 68 patients included in a [(18)F]flutemetamol amyloid PET imaging end-of-life study (GE067-007). At autopsy, AD pathology was determined and Abeta plaque pathology was classified into phases of its regional distribution (0-5). RESULTS: [(18)F]flutemetamol PET was universally positive in cases with advanced stage postmortem Abeta pathology (Abeta phases 4 and 5). Negative amyloid PET was universally observed in nondemented or non-AD dementia cases with initial Abeta phases 1 and 2, whereas 33.3% of the phase 3 cases were positive. CONCLUSIONS: [(18)F]flutemetamol amyloid PET detects primarily advanced stages of Abeta pathology in preclinical and symptomatic AD cases. PMID- 26141265 TI - A Qualitative Investigation of Somali Immigrant Perceptions of Disability: Implications for Genetic Counseling. AB - This study examined the potential utility of genetic counseling services for Somali immigrants by investigating their perceptions of disability. Five Somali women participated in structured interviews that assessed their perceptions of the nature, causes, and impact of disability, and care for persons with disabilities. Using a Heideggerian Hermeneutics qualitative method of analysis, six major themes emerged: (1) disability refers to both physical and mental conditions, with mental disability generally thought of first and as more severe; (2) in Somalia, the family cares for disabled family members, treating them as if they were "normal" (3) there are major cultural differences between Somalia and the United States in how persons with disabilities are treated; (4) caring for a person with a disability is stressful for the family; (5) Allah determines whether or not a child will be disabled, and this cannot be predicted or altered; and (6) family is the primary life focus, and therefore, risk of disability does not affect reproductive decisions. These themes suggest that traditional genetic counseling may have limited utility for Somali immigrants. We recommend several modifications to traditional genetic counseling for Somali patients that also may be useful for populations that have similar beliefs. PMID- 26141266 TI - Across the Spectrum: Case Studies in Genetic Counseling for Breast and Ovarian Cancer. AB - We present three vignettes based on participants counseled as part of a clinical research program. These include a young unaffected woman at risk for a familial mutation, a newly diagnosed breast cancer patient, and a woman with recurrent ovarian cancer. Through the use of detailed vignettes, multifaceted issues that arise in cancer genetic counseling are highlighted. PMID- 26141268 TI - Case Report: Depression vs. Early-Onset Alzheimer Disease: The Genetic Counselor's Role. AB - Awareness of depression in the differential diagnosis of Alzheimer disease is essential for genetic counselors seeing patients at risk for early-onset familial Alzheimer disease (EOFAD). The genetic counselor is in a unique position to recognize depression as the cause of symptoms mimicking early-onset Alzheimer disease. While generating a family medical history, the counselor can evoke significant emotional history as well. Based on this information, appropriate referrals can be given for neurological and psychological evaluation. The counselor also serves to explain EOFAD and the benefits and limitations of genetic testing for each individual patient. Whether or not patients choose testing, they can benefit from correct diagnosis of troublesome, or even debilitating, symptoms that imitate symptoms of the feared hereditary disease. PMID- 26141267 TI - Genetic Counseling and Screening Issues in Familial Dilated Cardiomyopathy. AB - Idiopathic dilated cardiomyopathy (IDC), a treatable condition characterized by left ventricular dilatation and systolic dysfunction of unknown cause, has only recently been recognized to have genetic etiologies. Although familial dilated cardiomyopathy (FDC) was thought to be infrequent, it is now believed that 30-50% of cases of IDC may be familial. Echocardiographic and electrocardiographic (ECG) screening of first-degree relatives of individuals with IDC and FDC is indicated because detection and treatment are possible prior to the onset of advanced, symptomatic disease. However, such screening often creates uncertainty and anxiety surrounding the significance of the results. Furthermore, FDC demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making genetic counseling complex. The provision of genetic counseling for IDC and FDC will require collaboration between cardiologists and genetics professionals, and may also improve the recognition of FDC, the availability of support services, and overall outcomes for patients and families. PMID- 26141269 TI - An integrated strategy for rapid and accurate determination of free and cell bound microcystins and related peptides in natural blooms by liquid chromatography-electrospray-high resolution mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry using both positive and negative ionization modes. AB - An integrated high resolution mass spectrometry (HRMS) strategy has been developed for rapid and accurate determination of free and cell-bound microcystins (MCs) and related peptides in water blooms. The natural samples (water and algae) were filtered for independent analysis of aqueous and sestonic fractions. These fractions were analyzed by MALDI-TOF/TOF-MS and ESI-Orbitrap-HCD MS. MALDI, ESI and the study of fragmentation sequences have been provided crucial structural information. The potential of combined positive and negative ionization modes, full scan and fragmentation acquisition modes (TOF/TOF and HCD) by HRMS and high resolution and accurate mass was investigated in order to allow unequivocal determination of MCs. Besides, a reliable quantitation has been possible by HRMS. This composition helped to decrease the probability of false positives and negatives, as alternative to commonly used LC-ESI-MS/MS methods. The analysis was non-target, therefore covered the possibility to analyze all MC analogs concurrently without any pre-selection of target MC. Furthermore, archived data was subjected to retrospective "post-targeted" analysis and a screening of other potential toxins and related peptides as anabaenopeptins in the samples was done. Finally, the MS protocol and identification tools suggested were applied to the analysis of characteristic water blooms from Spanish reservoirs. PMID- 26141270 TI - Solving signal instability to maintain the second-order advantage in the resolution and determination of multi-analytes in complex systems by modeling liquid chromatography-mass spectrometry data using alternating trilinear decomposition method assisted with piecewise direct standardization. AB - The application of calibration transfer methods has been successful in combination with near-infrared spectroscopy or other tools for prediction of chemical composition. One of the developed methods that can provide accurate performances is the piecewise direct standardization (PDS) method, which in this paper is firstly applied to transfer from one day to another the second-order calibration model based on alternating trilinear decomposition (ATLD) method built for the interference-free resolution and determination of multi-analytes in complex systems by liquid chromatography-mass spectrometry (LC-MS) in full scan mode. This is an example of LC-MS analysis in which interferences have been found, making necessary the use of second-order calibration because of its capacity for modeling this phenomenon, which implies analytes of interest can be resolved and quantified even in the presence of overlapped peaks and unknown interferences. Once the second-order calibration model based on ATLD method was built, the calibration transfer was conducted to compensate for the signal instability of LC-MS instrument over time. This allows one to reduce the volume of the heavy works for complete recalibration which is necessary for later accurate determinations. The root-mean-square error of prediction (RMSEP) and average recovery were used to evaluate the performances of the proposed strategy. Results showed that the number of calibration samples used on the real LC-MS data was reduced by using the PDS method from 11 to 3 while producing comparable RMSEP values and recovery values that were statistically the same (F-test, 95% confidence level) to those obtained with 11 calibration samples. This methodology is in accordance with the highly recommended green analytical chemistry principles, since it can reduce the experimental efforts and cost with regard to the use of a new calibration model built in modified conditions. PMID- 26141271 TI - Profiling of phytohormones in rice under elevated cadmium concentration levels by magnetic solid-phase extraction coupled with liquid chromatography tandem mass spectrometry. AB - Phytohormones, a collection of signal small molecules with various structures, regulate a series of physiological processes of plants. For instance, they regulate the growth and development, response to biotic and abiotic stresses. Quantification of trace endogenous phytohormones is essential to elucidate their molecular mechanisms in response to stresses. However, the structural and chemical diversity of phytohormones make it difficult to purify and enrich multiple phytohormones in one-step. In the current study, a method was developed to comprehensively profile phytohormones, including 8 cytokinins (CKs), indole-3 acetic acid (IAA), abscisic acid (ABA), jasmonic acid (JA) and 10 gibberellins (GAs) by Fe3O4@TiO2-based magnetic solid-phase extraction coupled with ultra performance liquid chromatography-electrospray tandem mass spectrometry (Fe3O4@TiO2-based MSPE-UPLC-MS/MS). In the proposed method, the phytohormones in the acetonitrile extract of plant tissues were captured and purified by one-step MSPE using Fe3O4@TiO2 as a sorbent prior to UPLC-MS/MS analysis. The sensitivity, accuracy and reproducibility of the proposed analytical method were demonstrated to satisfy the profiling of multiple phytohormones in plant tissue. We then further used the Fe3O4@TiO2-based MSPE-UPLC-MS/MS method to explore the change of phytohormones in rice under Cd stress. The results showed that CKs, IAA, ABA, JA and biological active GAs all increased under Cd stress, suggesting that these phytohormones may take part in response to Cd stress. The study may promote the further understanding of the physiological functions of phytohormones in response to Cd stress. PMID- 26141272 TI - Liquid chromatographic method for toxic biogenic amines in foods using a chaotropic salt. AB - Direct separation of biogenic amines by reversed-phase liquid chromatography (RPLC) is not an easy task because their basic and hydrophilic characteristics can lead to poor retention, column overloading, peak tailing, and hence low efficiency. Rather than routinely resorting to derivatization or using classical hydrophobic ion-pair reagents (IPR), this work proposes a new RPLC method making use of the chaotropic salt KPF6 as inorganic additive to an acidic acetonitrilic eluent to remedy the difficulties. Amine retention, overload behavior, peak shape, and column efficiency were significantly improved. The use of excess KPF6 led to a very slight decrease of amine retention. Depending on amine, the dependence of the logarithmic retention factor on the volume percent of acetonitrile could be reasonably linear or quite convex. Coupled with UV detection, the method was applied to trace analysis for six biogenic, aromatic or heterocyclic amines in three types of food after a sample cleanup, as necessary, by ion-pair extraction. The reliability of the whole analysis was demonstrated to be satisfactory. The proposed method outperforms existing methods in that it eliminates the need for long and cumbersome derivatization procedures without losing sensitivity; it also represents a good surrogate for classical ion-pair chromatography (IPC) because of the desirable hydrophilicity of chaotropic salts. PMID- 26141273 TI - Development and evaluation of electromembrane extraction across a hollow polymer inclusion membrane. AB - In this work, a new variation of the electromembrane extraction (EME) approach employing a hollow polymer inclusion membrane (HPIM) was developed. In this method, a HPIM was prepared by casting a solution of the desired proportions of cellulose acetate (CTA), tris(2-ethylhexyl)phosphate (TEHP) and di-(2 ethylhexyl)phosphoric acid (D2EHPA) in dichloromethane on glass capillary tubing. Three basic drugs namely amphetamine, methamphetamine, and 3,4-methylenedioxy-N methylamphetamine (MDMA) were selected as model analytes to evaluate the extraction performance of this new approach. The drugs were extracted from human plasma samples, through a 20MUm thickness HPIM, to an aqueous acceptor solution inside the lumen of the hollow membrane. Parameters affecting the extraction efficiency were investigated in detail. Under the optimized conditions, enrichment factors in the range of 97-103-fold were obtained from 3mL of sample solution with a 10min extraction time and an applied voltage of 300V across the HPIM. The detection limits of the method for the three drugs were in the range of 1.0-2.5ng/mL (at a signal/noise ratio of three), with relative standard deviations of between 6.4% and 7.9%. When the method was applied to spiked plasma samples, the relative recoveries ranged from 99.2% to 100.8%. Enrichment factors of 103, 99 and 97 were obtained for amphetamine, methamphetamine, and MDMA, respectively. A comparison was also made between the newly developed approach and EME using supported liquid membranes (SLM) as well as standard sample preparation methods (liquid-liquid extraction) used by the Toxicology Unit, Department of Chemistry, Malaysia. PMID- 26141274 TI - Metal free columns for determination of deoxynucleotide monophosphate by liquid chromatography/mass spectrometry and application to oligonucleotide. AB - We have developed a highly sensitive method for the analysis of deoxynucleotide monophosphates (dNMPs), which involves the use of liquid chromatography/mass spectrometry (LC/MS) and a new metal-free column. The new column solves the problem that the phosphate group in dNMPs interacts with the metal portion of the device or column. After optimization of the analytical conditions, the limits of detection (LODs) of dNMPs were from 5.4ng/g to 6.3ng/g. Those values were 10 times lower than the LODs of previous methods. We applied the method to the determination of the base composition and the quantification of 20-mer oligonucleotide. Despite use of a very small sample amount of 14.5ng, we were able to determine the base composition, and the result was consistent with theoretical values. We were also able to quantify the mass fraction of oligonucleotide with 8.2% expanded uncertainty (k=2). By means of the developed method, we were able to analyze dNMPs with high sensitivity as well as determine the base composition and quantify the mass fraction of oligonucleotide despite use of a small amount of sample. PMID- 26141275 TI - Jacket-free stir bar sorptive extraction with bio-inspired polydopamine functionalized immobilization of cross-linked polymer on stainless steel wire. AB - Stainless steel wire (SSW) is a good substrate for stir bar sorptive extraction (SBSE). However, it is still a challenge to immobilize commonly used cross-linked polymers onto SSW. In this work, we present a new approach for immobilization of the cross-linked organic polymer onto SSW for jacket-free SBSE. A dopamine derivative was firstly synthesized; by introducing a mussel-inspired polydopamine process, a stable coating layer was finally generated on the surface of SSW. Secondly, the cross-linked polymer was synthesized on the polydopamine-modified SSW by using acetonitrile as the porogen, acrylamide (AA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker and 2,2' azobis (2-methylpropionitrile) as the initiator. A diluted pre-polymerization solution was carefully prepared to generate a thin layer of the polymer. The prepared poly(EGDMA-AA)-modified stir bar showed high stability and good tolerance toward stirring, ultrasonication, organic solvents, and strong acidic and basic conditions. Morphology and structure characterization of coatings were performed by scanning electron microscopy and Fourier transform infrared spectra, respectively. The prepared poly(EGDMA-AA)-modified stir bar showed great extraction efficiency toward protoberberines, with enrichment factors of 19-42. An SBSE-HPLC method was also developed for quantitative analysis of protoberberines. The method showed low limits of detection (0.06-0.15 ng mL(-1)), wide linear range (0.5-400 ng mL(-1)), good linearity (R>=0.9980) and good reproducibility (RSD<=3.60% for intra-day, RSD<=4.73% for inter-day). The developed method has been successfully applied to determine protoberberines in herb and rat plasma samples, with recoveries of 88.53-114.61%. PMID- 26141276 TI - Simulated moving bed separation of agarose-hydrolyzate components for biofuel production from marine biomass. AB - The economically-efficient separation of galactose, levulinic acid (LA), and 5 hydroxymethylfurfural (5-HMF) in acid hydrolyzate of agarose has been a key issue in the area of biofuel production from marine biomass. To address this issue, an optimal simulated moving bed (SMB) process for continuous separation of the three agarose-hydrolyzate components with high purities, high yields, and high throughput was developed in this study. As a first step for this task, the adsorption isotherm and mass-transfer parameters of each component on the qualified adsorbent were determined through a series of multiple frontal experiments. The determined parameters were then used in optimizing the SMB process for the considered separation. Finally, the optimized SMB process was tested experimentally using a self-assembled SMB unit with four zones. The SMB experimental results and the relevant computer simulations verified that the developed process in this study was quite successful in the economically efficient separation of galactose, LA, and 5-HMF in a continuous mode with high purities and high yields. It is thus expected that the developed SMB process in this study will be able to serve as one of the trustworthy ways of improving the economic feasibility of biofuel production from marine biomass. PMID- 26141277 TI - Fabrication of zeolitic imidazolate framework-8-methacrylate monolith composite capillary columns for fast gas chromatographic separation of small molecules. AB - A composite zeolitic imidazolate framework-8 (ZIF-8) with a butyl methacrylate-co ethylene dimethacrylate (BuMA-co-EDMA) monolithic capillary column (33.5cm long*250MUm i.d.) was fabricated to enhance the separation efficiency of methacrylate monoliths toward small molecules using conventional low-pressure gas chromatography in comparison with a neat butyl methacrylate-co-ethylene dimethacrylate (BuMA-co-EDMA) monolithic capillary column (33.5cm long*250MUm i.d.). The addition of 10mgmL(-1) ZIF-8 micro-particles increased the BET surface area of BuMA-co-EDMA by 3.4-fold. A fast separation of five linear alkanes in 36s with high resolution (Rs>=1.3) was performed using temperature program. Isothermal separation of the same sample also showed a high efficiency (3315platesm(-1) for octane) at 0.89min. Moreover, the column was able to separate skeletal isomers, such as iso-octane/octane and 2-methyl octane/nonane. In addition, an iso-butane/iso-butylene gas mixture was separated at ambient temperature. Comparison with an open tubular TR-5MS column (30m long*250MUm i.d.) revealed the superiority of the composite column in separating the five-membered linear alkane mixture with 4-5 times increase in efficiency and a total separation time of 0.89min instead of 4.67min. A paint thinner sample was fully separated using the composite column in 2.43min with a good resolution (Rs>=0.89). The perfect combination between the polymeric monolith, with its high permeability, and ZIF-8, with its high surface area and flexible 0.34nm pore openings, led to the fast separation of small molecules with high efficiency and opened a new horizon in GC applications. PMID- 26141278 TI - Analyzing the success of the volume-based waste fee system in South Korea. AB - For more than a decade, South Korea has been ranked first among the OECD (Organization for Economic Cooperation and Development) members in their municipal solid waste (MSW) recycling rate. One of the major contributing factors for its outstanding MSW recycling performance is the volume-based waste fee (VWF) system implemented in 1995. Despite the perceived success of VWF, there has been few research conducted that has sought to demonstrate the success of the policy in an empirical manner. Research conducted currently on VWF in South Korea tends to have limitations in empirical approaches and identifying the intervention effect of VWF on recycling performance. This study attempts to empirically test whether the adoption of VWF positively affected recycling performance in Korea over time. The findings suggest that although there was a dramatic increase of the recycling rate with the introduction of VWF in 1995, Korea's MSW recycling performance settled back again and showed the constant pace after the intervention. No significant differences in recycling rate were found between before and after 1995 period. In conclusion, implications and suggestions for both research and practice are proposed. PMID- 26141279 TI - Lignocellulose-derived inhibitors improve lipid extraction from wet Rhodococcus opacus cells. AB - Extracting lipids from oleaginous microbial cells in a cost effective and environmentally compatible manner remains a critical challenge in developing manufacturing paradigms for advanced liquid biofuels. In this study, a new approach using microbial growth inhibitors from lignocellulose-derived feedstocks was used to extract lipids efficiently from wet cell mass of the oleaginous bacterium Rhodococcus opacus MITXM-61. Nine common lignocellulose-derived inhibitors for treatment of cells prior to solvent extraction were used and evaluated for their efficiency of lipid extraction from the cells. When the inhibitors were individually examined, formic acid and furfural showed the highest extraction efficiency of lipids from wet cell mass. Multiple extractions of lipids with methanol from wet cell mass pretreated with combined common inhibitors or hardwood hydrolysate comprising lignocellulose-derived inhibitors resulted in lipid recovery of greater than 85% of total lipids, a 1.7-fold increase of lipid extraction as compared to those in the absence of the inhibitors. PMID- 26141280 TI - The effect of iron dosing on reducing waste activated sludge in the oxic-settling anoxic process. AB - This study evaluates the biological solid reduction in a conventional activated sludge system with an anoxic/anaerobic side stream reactor receiving 1/10 of return sludge mass. Influent iron concentrations and feeding modes were changed to explore the consistency between the influent iron concentration and yield values and to assess the impact of feeding pattern. The results indicated that sludge reduction occurs during alternately exposure of sludge to aerobic and anoxic/anaerobic conditions in a range of 38-87%. The sludge reduction values reached a maximum level with the higher iron concentrations. Thus, it is concluded that this configuration is more applicable for plants receiving high iron concentrations in the wastewaters. PMID- 26141281 TI - Stabilisation of microalgae: Iodine mobilisation under aerobic and anaerobic conditions. AB - Mobilisation of iodine during microalgae stabilisation was investigated, with the view of assessing the potential of stabilised microalgae as an iodine-rich fertiliser. An iodine-rich waste microalgae (0.35 +/- 0.05 mg I g(-1) VS(added)) was stabilised under aerobic and anaerobic conditions. Iodine mobilisation was linearly correlated with carbon emission, indicating iodine was in the form of organoiodine. Comparison between iodine and nitrogen mobilisation relative to carbon emission indicated that these elements were, at least in part, housed separately within the cells. After stabilisation, there were 0.22 +/- 0.05 and 0.19 +/- 0.01 mg g(-1) VS(added) iodine remaining in the solid in the aerobic and anaerobic processed material respectively, meaning 38 +/- 5.0% (aerobic) and 50 +/- 8.6% (anaerobic) of the iodine were mobilised, and consequently lost from the material. The iodine content of the stabilised material is comparable to the iodine content of some seaweed fertilisers, and potentially satisfies an efficient I-fertilisation dose. PMID- 26141282 TI - Nitrogen removal characteristics of a heterotrophic nitrifier Acinetobacter junii YB and its potential application for the treatment of high-strength nitrogenous wastewater. AB - Acinetobacter junii YB was found to exhibit efficient heterotrophic nitrification and aerobic denitrification ability, with the maximum ammonium, nitrite and nitrate removal rate of 8.82, 8.45 and 7.98 mg/L/h, respectively. Meanwhile, ammonium was found to be removed preferentially in the process of simultaneous nitrification and denitrification in mixed N-sources. The successful PCR amplification of hao, napA and nirS genes further provided additional evidence of heterotrophic nitrification and aerobic denitrification by strain YB. In addition, orthogonal test showed that dissolved oxygen was the most important determinant of nitrite removal, and the optimal conditions were C/N 15, pH 7.0, 37 degrees C and 200 rpm. Furthermore, stable nitrogen and organics removal were achieved by one-time dosing of enriched bacteria in a sequencing batch reactor. The inoculation of strain YB significantly improved the denitrification efficiency with minimal accumulation of nitrified products, which demonstrated high potential of the isolate for future practical applications. PMID- 26141283 TI - Evaluation and characterization during the anaerobic digestion of high-strength kitchen waste slurry via a pilot-scale anaerobic membrane bioreactor. AB - The anaerobic digestion of high-strength kitchen waste slurry via a pilot-scale anaerobic membrane bioreactor (AnMBR) was investigated at two different operational modes, including no sludge discharge and daily sludge discharge of 20 L. The AnMBR provided excellent and reliable permeate quality with high COD removal efficiencies over 99%. The obvious accumulations of long chain fatty acids (LCFAs) and Ca(2+) were found in the anaerobic digester by precipitation and agglomeration. Though the physicochemical process contributed to attenuating the free LCFAs toxicity on anaerobic digestion, the digestion efficiency was partly influenced for the low bioavailability of those precipitates. Moreover, higher organic loading rate (OLR) of 5.8 kg COD/(m(3) d) and digestion efficiency of 78% were achieved as the AnMBR was stably operated with sludge discharge, where the membrane fouling propensity was also alleviated, indicating the crucial significance of SRT control on the treatment of high-strength kitchen waste slurry via AnMBRs. PMID- 26141284 TI - Efficient removal of arsenic from water using a granular adsorbent: Fe-Mn binary oxide impregnated chitosan bead. AB - A novel sorbent of Fe-Mn binary oxide impregnated chitosan bead (FMCB) was fabricated through impregnating Fe-Mn binary oxide into chitosan matrix. The FMCB is sphere-like with a diameter of 1.6-1.8 mm, which is effective for both As(V) and As(III) sorption. The maximal sorption capacities are 39.1 and 54.2 mg/g, respectively, outperforming most of reported granular sorbents. The arsenic was mainly removed by adsorbing onto the Fe-Mn oxide component. The coexisting SO4(2 ), HCO3(-) and SiO3(2-) have no great influence on arsenic sorption, whereas, the HPO4(2-) shows negative effects. The arsenic-loaded FMCB could be effectively regenerated using NaOH solution and repeatedly used. In column tests, about 1500 and 3200 bed volumes of simulated groundwater containing 233 MUg/L As(V) and As(III) were respectively treated before breakthrough. These results demonstrate the superiority of the FMCB in removing As(V) and As(III), indicating that it is a promising candidate for arsenic removal from real drinking water. PMID- 26141285 TI - Production of technical-grade sodium citrate from glycerol-containing biodiesel waste by Yarrowia lipolytica. AB - The production of technical-grade sodium citrate from the glycerol-containing biodiesel waste by Yarrowia lipolytica was studied. Batch experiments showed that citrate was actively produced within 144 h, then citrate formation decreased presumably due to inhibition of enzymes involved in this process. In contrast, when the method of repeated batch cultivation was used, the formation of citrate continued for more than 500 h. In this case, the final concentration of citrate in the culture liquid reached 79-82 g/L. Trisodium citrate was isolated from the culture liquid filtrate by the addition of a small amount of NaOH, so that the pH of the filtrate increased to 7-8. This simple and economic isolation procedure gave the yield of crude preparation containing trisodium citrate 5.5-hydrate up to 82-86%. PMID- 26141286 TI - Assessment of the influence of energy density and feedstock transport distance on the environmental performance of methane from maize silages. AB - In Europe, thanks to public subsidy, the production of electricity from anaerobic digestion (AD) of agricultural feedstock has considerably grown and several AD plants were built. When AD plants are concentrated in specific areas (e.g., Northern Italy), increases of feedstock' prices and transport distances can be observed. In this context, as regards low-energy density feedstock, the present research was designed to estimate the influence of the related long-distance transport on the environmental performances of the biogas-to-electricity process. For this purpose the following transport systems were considered: farm trailers and trucks. For small distances (<5 km), the whole plant silage shows the lowest impact; however, when distances increase, silages with higher energy density (even though characterised by lower methane production per hectare) become more environmentally sustainable. The transport by trucks achieves better environmental performances especially for distances greater than 25 km. PMID- 26141287 TI - Effect of the molecular structure of lignin-based polyoxyethylene ether on enzymatic hydrolysis efficiency and kinetics of lignocelluloses. AB - Effect of the molecular structure of lignin-based polyoxyethylene ether (EHL-PEG) on enzymatic hydrolysis of Avicel and corn stover was investigated. With the increase of PEG contents and molecular weight of EHL-PEG, glucose yield of corn stover increased. EHL-PEG enhanced enzymatic hydrolysis of corn stover significantly at buffer pH 4.8-5.5. Glucose yield of corn stover at 20% solid content increased from 32.8% to 63.8% by adding EHL-PEG, while that with PEG4600 was 54.2%. Effect of EHL-PEG on enzymatic hydrolysis kinetics of cellulose film was studied by quartz crystal microbalance with dissipation monitoring (QCM-D) and atomic force microscopy (AFM). An enhancing mechanism of EHL-PEG on enzymatic hydrolysis kinetics of cellulose was proposed. Cellulase aggregates dispersed by EHL-PEG excavated extensive cavities into the surface of cellulose film, making the film become more loose and exposed. After the maximum enzymatic hydrolysis rate, the film was mainly peeled off layer by layer until equilibrium. PMID- 26141288 TI - Extracellular polymeric substances govern the development of biofilm and mass transfer of polycyclic aromatic hydrocarbons for improved biodegradation. AB - The hypothesis that extracellular polymeric substances (EPS) affect the formation of biofilms for subsequent enhanced biodegradation of polycyclic aromatic hydrocarbons was tested. Controlled formation of biofilms on humin particles and biodegradation of phenanthrene and pyrene were performed with bacteria and EPS extracted bacteria of Micrococcus sp. PHE9 and Mycobacterium sp. NJS-P. Bacteria without EPS extraction developed biofilms on humin, in contrast the EPS-extracted bacteria could not attach to humin particles. In the subsequent biodegradation of phenanthrene and pyrene, the biodegradation rates by biofilms were significantly higher than those of EPS-extracted bacteria. Although, both the biofilms and EPS extracted bacteria showed increases in EPS contents, only the EPS contents in biofilms displayed significant correlations with the biodegradation efficiencies of phenanthrene and pyrene. It is proposed that the bacterial-produced EPS was a key factor to mediate bacterial attachment to other surfaces and develop biofilms, thereby increasing the bioavailability of poorly soluble PAH for enhanced biodegradation. PMID- 26141289 TI - Theoretical study of precision and accuracy of strain analysis by nano-beam electron diffraction. AB - Measurement of lattice strain is important to characterize semiconductor nanostructures. As strain has large influence on the electronic band structure, methods for the measurement of strain with high precision, accuracy and spatial resolution in a large field of view are mandatory. In this paper we present a theoretical study of precision and accuracy of measurement of strain by convergent nano-beam electron diffraction. It is found that the accuracy of the evaluation suffers from halos in the diffraction pattern caused by a variation of strain within the area covered by the focussed electron beam. This effect, which is expected to be strong at sharp interfaces between materials with different lattice plane distances, will be discussed for convergent-beam electron diffraction patterns using a conventional probe and for patterns formed by a precessing electron beam. Furthermore, we discuss approaches to optimize the accuracy of strain measured at interfaces. The study is based on the evaluation of diffraction patterns simulated for different realistic structures that have been investigated experimentally in former publications. These simulations account for thermal diffuse scattering using the frozen-lattice approach and the modulation-transfer function of the image-recording system. The influence of Poisson noise is also investigated. PMID- 26141291 TI - [Follow-up of urothelial carcinoma: Review of the Cancer Committee of the French Association of Urology]. AB - INTRODUCTION: Cancer Committee of the French Association of Urology (CCAFU) conducted a literature review concerning the follow-up of urothelial carcinomas and provides recommendations for monitoring. MATERIAL AND METHODS: A bibliographic research in French and English using PubMed was carried out from 1990 to 2014 using the keywords "urothelial carcinoma", "follow-up", "prognosis", and "recurrence". RESULTS: Rhythm and tools of follow-up (cytology, endoscopy, CT urography) for non muscle invasive bladder cancer (NMIBC) have to be adjusted to the recurrence and progression risk defined by the EORTC tables. After radical treatment of muscle invasive bladder cancer (MIBC), follow-up is based on endoscopy, cytology and CT-urography. Monitoring of the urethra must be adapted to the recurrence factors and continued for at least 5 years. The monitoring of upper tract should be continued for life. In case of conservative treatment for MIBC, early endoscopy and imaging reassessment is required. After radical treatment of upper urinary tract tumour (UTUC), cystoscopy and cytology are essential because of the frequency of bladder recurrence in the first three years. Conservative management of UTUC requires strict monitoring including flexible ureteroscopy. CONCLUSION: Oncologic follow-up of urothelial carcinomas is adapted according to tumour stage and grade, location and treatment modality thus defining the risk of recurrence over time. PMID- 26141290 TI - Increased gene copy number of HER2 and concordant protein overexpression found in a subset of eyelid sebaceous gland carcinoma indicate HER2 as a potential therapeutic target. AB - PURPOSE: To identify crucial molecular alterations of receptor tyrosine kinases that can be used as potential therapeutic targets for eyelid sebaceous gland carcinoma (SbGC). METHODS: The expression levels of HER2, EGFR, C-MET, and FGFR1 were determined by immunohistochemistry (IHC). The copy numbers of the HER2, EGFR, C-MET, and FGFR1 genes were assessed by fluorescence in situ hybridization. The IHC and molecular results were correlated with the clinical parameters. RESULTS: A total of 49 patients with eyelid SbGC were included in this study. HER2, EGFR, C-MET, and FGFR1 protein expression was detected in 8 of 44 (16.3 %), 8 of 45 (17.8 %), 3 of 35 (8.6 %), and 0 of 45 patient samples, respectively. Increased copy numbers of the HER2 gene were found in 5 of 42 patient samples (11.9 %), including two with amplification (4.7 %) and three with polysomy (7.2 %). EGFR amplification was found in 2 of 33 (6.1 %) and FGFR1 amplification in 4 of 33 patient samples (12.1 %; high-level amplification in one and low-level amplification in three). None of the samples examined exhibited C-MET amplification. Gene copy number of the HER2 gene was correlated with its protein expression (p < 0.0001), whereas copy number of EGFR, C-MET, or FGFR1 was not correlated with protein expression. However, samples with EGFR amplification also exhibited a high level of expression of this protein. CONCLUSIONS: Extra copies of the HER2, EGFR, and FGFR1 genes were identified in a 6-12 % of eyelid SbGCs. A high level of concordant HER2 expression detected by immunohistochemistry can be predictive of a copy number gain of the HER2 gene. Our data suggest that the therapeutic targeting of HER2 might benefit for a subset of patients with periocular SbGCs. PMID- 26141292 TI - Preterm birth and future risk of maternal cardiovascular disease - is the association independent of smoking during pregnancy? AB - BACKGROUND: While the association of preterm birth and the risk of maternal cardiovascular disease (CVD) has been well-documented, most studies were limited by the inability to account for smoking during pregnancy - an important risk factor for both preterm birth and CVD. This study aimed to determine whether the increased future risk of maternal cardiovascular disease (CVD) associated with preterm birth is independent of maternal smoking during pregnancy. METHODS: A population-based record linkage study of 797,056 women who delivered a singleton infant between 1994 and 2011 in New South Wales, Australia was conducted. Birth records were linked to the mothers' subsequent hospitaliation or death from CVD. Preterm births were categorised as late (35-36 weeks), moderate (33-34 weeks), or extreme (<=32 weeks); and as spontaneous or indicated. Cox proportional hazard regression was used to estimate adjusted hazard ratios (AHR) [95 % CI]. RESULTS: During the study period, 59,563 women (7.5 %) had at least one preterm birth. After adjustment for CVD risk factors other than smoking, AHR [95 % CI] of CVD among women who ever had a preterm birth was 1.78 [1.61-1.96]. Associations were greater for extreme (AHR = 1.98 [1.63-2.42]) and moderate (AHR = 2.06 [1.69 2.51]) than late preterm birth (AHR = 1.63 [1.44-1.85]), for indicated (AHR = 2.04 [1.75-2.38]) than spontaneous preterm birth (AHR = 1.65 [1.47-1.86]), and for having >= two (AHR = 2.29[1.75-2.99]) than having one preterm birth (AHR = 1.73[1.57-1.92]). A further adjustment for maternal smoking attenuated, but did not eliminate, the associations. Smoking during pregnancy was also independently associated with maternal CVD risks, with associations being stronger for mothers who smoked during last pregnancy (AHR = 2.07 [1.93-2.23]) than mothers who smoked during a prior pregnancy (AHR = 1.64 [1.41-1.90]). CONCLUSIONS: Associations of preterm birth and maternal CVD risk are independent of maternal smoking during pregnancy. This underscores the importance of smoking cessation in reducing CVD and suggests that a history of preterm delivery (especially if severe, indicated or recurrent) identifies women who could be targeted for CVD screening and preventative therapies. PMID- 26141293 TI - Validation of neutron flux redistribution factors in JSI TRIGA reactor due to control rod movements. AB - For efficient utilization of research reactors, such as TRIGA Mark II reactor in Ljubljana, it is important to know neutron flux distribution in the reactor as accurately as possible. The focus of this study is on the neutron flux redistributions due to control rod movements. For analyzing neutron flux redistributions, Monte Carlo calculations of fission rate distributions with the JSI TRIGA reactor model at different control rod configurations have been performed. Sensitivity of the detector response due to control rod movement have been studied. Optimal radial and axial positions of the detector have been determined. Measurements of the axial neutron flux distribution using the CEA manufactured fission chambers have been performed. The experiments at different control rod positions were conducted and compared with the MCNP calculations for a fixed detector axial position. In the future, simultaneous on-line measurements with multiple fission chambers will be performed inside the reactor core for a more accurate on-line power monitoring system. PMID- 26141294 TI - L shell X-ray fluorescence parameters of Pb in phthalocyanine complexes. AB - The L shell X-ray intensity ratios Li/Lalpha (i=l, beta and gamma), the production cross-sections sigma(Li) (i=l, alpha, beta and gamma) and the L3 subshell fluorescence yields omega(L3) have been investigated for the element Pb in the phthalocyanine complexes. The measurements have been performed using an (241)Am annular radioactive source and an Ultra-LEGe detector with a resolution of 150 eV at 5.9 keV. The experimental values have been compared with the theoretical values of pure Pb element. PMID- 26141295 TI - Applying a low energy HPGe detector gamma ray spectrometric technique for the evaluation of Pu/Am ratio in biological samples. AB - The estimation of Pu/(241)Am ratio in the biological samples is an important input for the assessment of internal dose received by the workers. The radiochemical separation of Pu isotopes and (241)Am in a sample followed by alpha spectrometry is a widely used technique for the determination of Pu/(241)Am ratio. However, this method is time consuming and many times quick estimation is required. In this work, Pu/(241)Am ratio in the biological sample was estimated with HPGe detector based measurements using gamma/X-rays emitted by these radionuclides. These results were compared with those obtained from alpha spectroscopy of sample after radiochemical analysis and found to be in good agreement. PMID- 26141296 TI - Bioneutronics: Thermal scattering in organics tissues and its impact on BNCT dosimetry. AB - Neutron transport calculation is a key factor in BNCT numerical dosimetry assessments where thermal neutron flux is intimately related to the neutron dose, specially, the therapeutic boron dose. In this work, numerical calculations in phantoms were performed to determine the importance of utilizing the appropriate thermal scattering treatment for different organic tissues. Two thermal treatments for the neutron scattering were included in the simulations: hydrogen bounded in bulk water and hydrogen bounded in a lipid like carbon chain (polyethylene). The results showed difference between both thermal treatments that can reach several percent points depending on the type of source and irradiated geometry. PMID- 26141297 TI - Nuclear model calculation and targetry recipe for production of 110mIn. AB - (110m)In is potentially an important positron emitting that can be used in positron emission tomography. In this work, the excitation functions and production yields of (110)Cd(d, 2n), (111)Cd(d, 3n), (nat)Cd(d, xn), (110)Cd(p, n), (111)Cd(p, 2n), (112)Cd(p, 3n) and (nat)Cd(p, xn) reactions to produce the (110m)In were calculated using nuclear model code TALYS and compared with the experimental data. The yield of isomeric state production of (110)In was also compared with ground state production ones to reach the optimal energy range of projectile for the high yield production of metastable state. The results indicate that the (110)Cd(p, n)(110m)In is a high yield reaction with an isomeric ratio (sigma(m)/sigma(g)) of about 35 within the optimal incident energy range of 15-5 MeV. To make the target, cadmium was electroplated on a copper substrate in varying electroplating conditions such as PH, DC current density, temperature and time. A set of cold tests were also performed on the final sample under several thermal shocks to verify target resistance. The best electroplated cadmium target was irradiated with 15 MeV protons at current of 100 uA for one hour and the production yield of (110m)In and other byproducts were measured. PMID- 26141298 TI - How to interpret visual fields. PMID- 26141300 TI - Correction. PMID- 26141299 TI - Headache management: pharmacological approaches. AB - Headache is one of the most common conditions presenting to the neurology clinic, yet a significant proportion of these patients are unsatisfied by their clinic experience. Headache can be extremely disabling; effective treatment is not only essential for patients but is rewarding for the physician. In this first of two parts review of headache, we provide an overview of headache management, emerging therapeutic strategies and an accessible interpretation of clinical guidelines to assist the busy neurologist. PMID- 26141301 TI - Validation of the Polish version of the Knee injury and Osteoarthritis Outcome Score (KOOS) in patients with osteoarthritis undergoing total knee replacement. AB - OBJECTIVE: To test the clinimetric properties and to evaluate the internal consistency, validity and reliability of the Polish version of the Knee injury and Osteoarthritis Outcome Score (KOOS) in older patients with end-stage knee osteoarthritis undergoing total knee replacement (TKR). DESIGN AND SETTING: A prospective cohort study performed at the university hospital and the outpatient clinic. METHODS: The patients were asked to complete the KOOS questionnaire and the Short Form 36 Health Survey. We evaluated floor/ceiling effects, reliability (using Cronbach's alpha, intraclass correlation coefficients (ICC) and measurement error), structural validity (performing exploratory principal factor analysis), construct validity (with the use of 3 a priori hypotheses) and responsiveness (using data obtained before and after the surgery, and described by Global Perceived Effect, effect size and standardised response mean). RESULTS: The study consisted of 68 participants (mean age 68.8, 82% women). The floor effects were found prior to surgery for the subscales Sports and Recreation Function, and Quality of Life. The Cronbach's alpha was from 0.90 to 0.92 for all subscales, indicating excellent internal consistency. The test-retest reliability at follow-up was excellent, with ICCs ranging from 0.81 to 0.86 for all KOOS subscales. The minimal detectable change ranged from 18.2 to 24.3 on an individual level and from 2.4 to 2.9 on a group level. All KOOS items were relevant, and all a priori established hypotheses were supported. Responsiveness was confirmed with a statistically significant correlation between all KOOS subscales and the Global Perceived Effect score (ranging from 0.56 to 0.70, p<0.001). CONCLUSIONS: The Polish version of KOOS demonstrated good reliability, validity and responsiveness for use in patient groups that had undergone TKR. Since the smallest change considered clinically relevant cannot reliably be detected in individual cases, the Polish version of KOOS is advocated for assessment of groups of patients. PMID- 26141303 TI - Correction. PMID- 26141302 TI - 'Errors' and omissions in paper-based early warning scores: the association with changes in vital signs--a database analysis. AB - OBJECTIVES: To understand factors associated with errors using an established paper-based early warning score (EWS) system. We investigated the types of error, where they are most likely to occur, and whether 'errors' can predict subsequent changes in patient vital signs. METHODS: Retrospective analysis of prospectively collected early warning system database from a single large UK teaching hospital. RESULTS: 16,795 observation sets, from 200 postsurgical patients, were collected. Incomplete observation sets were more likely to contain observations which should have led to an alert than complete observation sets (15.1% vs 7.6%, p<0.001), but less likely to have an alerting score correctly calculated (38.8% vs 30.0%, p<0.001). Mis-scoring was much more common when leaving a sequence of three or more consecutive observation sets with aggregate scores of 0 (55.3%) than within the sequence (3.0%, p<0.001). Observation sets that 'incorrectly' alerted were more frequently followed by a correctly alerting observation set than error-free non-alerting observation sets (14.7% vs 4.2%, p<0.001). Observation sets that 'incorrectly' did not alert were more frequently followed by an observation set that did not alert than error-free alerting observation sets (73.2% vs 45.8%, p<0.001). CONCLUSIONS: Missed alerts are particularly common in incomplete observation sets and when a patient first becomes unstable. Observation sets that 'incorrectly' alert or 'incorrectly' do not alert are highly predictive of the next observation set, suggesting that clinical staff detect both deterioration and improvement in advance of the EWS system by using information not currently encoded within it. Work is urgently needed to understand how best to capture this information. PMID- 26141304 TI - Can a 3-hour educational workshop and the provision of practical tools encourage family physicians to prescribe physical activity as medicine? A pre-post study. AB - OBJECTIVES: To increase, in our sample, the proportion of family physicians who provided their patients with written physical activity prescriptions after the delivery of a 3-hour educational workshop with the provision of practical tools to facilitate behaviour change. DESIGN: A pre-post study. SETTING: Abbotsford and Mission, British Columbia. PARTICIPANTS: All 158 physicians registered with the Abbotsford (121) or Mission (37) Divisions of Family Practice were invited to participate. INTERVENTION: A 3-hour educational workshop combined with practical tools. Educational content of the workshop included (1) assessing patients' physical activity levels, (2) using motivational interviewing techniques to encourage physical activity and (3) providing written physical activity prescriptions when appropriate. Practical tools to facilitate physician behaviour changes included a 'physical activity vital sign', and copies of the Exercise is Medicine Canada Prescription Pad. Participating physicians completed a bespoke questionnaire before and 4 weeks after their attendance at the workshop. OUTCOME MEASURES: The primary outcome was the change in the proportion of family physicians who reported providing written physical activity prescriptions. Exploratory outcomes included changes in other physical activity prescription behaviours, the perceived importance of various barriers to prescription, and knowledge and confidence in regards to physical activity prescription. McNemar's test evaluated changes in proportions before and after the workshop, while Wilcoxon signed-rank tests evaluated changes in Likert data. RESULTS: 25 family physicians completed the baseline questionnaire and attended the workshop, with 100% follow-up response rate. The proportion of family physicians who reported providing written physical activity prescriptions in their clinical practice increased significantly (p<0.05), from 10 (40%) at baseline to 17 (68%) 4 weeks after the intervention. CONCLUSIONS: Educational workshops combined with practical tools appear to be a promising method to encourage the use of written physical activity prescriptions among family physicians in this setting, over the short term. PMID- 26141305 TI - Efficacy and Safety of Pergoveris in Assisted Reproductive Technology--ESPART: rationale and design of a randomised controlled trial in poor ovarian responders undergoing IVF/ICSI treatment. AB - INTRODUCTION: The results of a recent meta-analysis showed that adding recombinant human luteinising hormone (r-hLH) to recombinant human follicle stimulating hormone (r-hFSH) for ovarian stimulation was beneficial in poor responders, resulting in a 30% relative increase in the clinical pregnancy rate compared with r-hFSH monotherapy. However, a limitation of the meta-analysis was that the included studies used heterogeneous definitions of poor ovarian response (POR). Furthermore, the use of r-hLH supplementation during ovarian stimulation is a topic of ongoing debate, and well-designed, adequately powered, multicentre, randomised controlled trials in this setting are warranted. Therefore, the objective of the ESPART trial is to explore the possible superiority of a fixed dose combination of r-hFSH plus r-hLH over r-hFSH monotherapy in patients with POR, as per a definition aligned with the European Society of Human Reproduction and Embryology (ESHRE) Bologna criteria. METHODS AND ANALYSIS: Phase III, randomised, single-blind, parallel-group trial in women undergoing in vitro fertilisation and/or intracytoplasmic sperm injection. Approximately 946 women aged 18-<41 years from 18 countries will be randomised (1:1) to receive a fixed dose combination of r-hFSH plus r-hLH in a 2:1 ratio (Pergoveris) or r-hFSH monotherapy (GONAL-f). The primary end point is the total number of retrieved oocytes per participant. Secondary end points include: ongoing pregnancy rate, live birth rate, implantation rate, biochemical pregnancy rate and clinical pregnancy rate. Safety end points include: incidence and severity of ovarian hyperstimulation syndrome, and of adverse events and serious adverse events. ETHICS AND DISSEMINATION: The study will be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki, with the International Conference on Harmonisation-Good Clinical Practice guidelines and all applicable regulatory requirements. All participants will provide written informed consent prior to entry. The results of this study will be publically disseminated. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov identifier: NCT02047227; EudraCT Number: 2013-003817-16; Clinical Trial Protocol Number: EMR200061-005 V.3.0, 15 April 2014. PMID- 26141306 TI - Cathasept Line Lock and Microbial Colonization of Tunneled Hemodialysis Catheters: A Multicenter Randomized Controlled Trial. AB - BACKGROUND: Catheter-related bloodstream infections (CRBSIs) cause morbidity and mortality in hemodialysis (HD) patients. Cathasept (tetra-sodium EDTA) solution has antimicrobial and anticoagulant activities. STUDY DESIGN: Multicenter prospective randomized controlled study. SETTING & PARTICIPANTS: 117 maintenance HD patients with confirmed uncolonized tunneled HD catheters from 4 HD centers. INTERVENTION: Patients were randomly assigned to receive Cathasept 4% locks (Cathasept group) or stayed with heparin 5,000 U/mL locks (heparin group), filled thrice weekly according to catheter lumen volume until the catheter was removed or for a maximum of 8 months. OUTCOMES: Primary outcome was clinically significant microbial colonization of the catheter, defined as a through-catheter quantitative blood culture yielding >= 1,000 colony-forming units/mL of bacteria or yeast. Secondary outcomes included CRBSI rate, catheter patency, and biomarkers of inflammation and anemia. MEASUREMENTS: Weekly through-catheter quantitative blood culture, high-sensitivity C-reactive protein fortnightly, and full blood count and ferritin monthly. RESULTS: Incidence rates of catheter colonization were 0.14/1,000 catheter-days in the Cathasept group and 1.08/1,000 catheter-days in the heparin group (incidence rate ratio [IRR], 0.13; 95% CI, 0.003-0.94; P=0.02). CRBSI rates were 0.28/1,000 catheter-days in the Cathasept group and 0.68/1,000 catheter days in the heparin group (IRR, 0.40; 95% CI, 0.08 2.09; P=0.3). The proportion of dialysis sessions with achieved prescribed blood flow rate was significantly lower in the Cathasept group (66.8% vs 75.3%; P<0.001), with more patients requiring thrombolytic locks or infusions to maintain catheter patency (22 vs 9; P=0.01). Mean high-sensitivity C-reactive protein level was 11.6+/-5.3 (SE) mg/L lower for patients in the heparin group (P=0.03). Anemia marker levels were similar in both groups. LIMITATIONS: Study was underpowered to assess effect on CRBSI, terminated early due to slow recruitment, and not double blinded. CONCLUSIONS: Cathasept significantly reduced tunneled hemodialysis catheter colonization, but the reduction in CRBSIs was not statistically significant, and it was associated with more thrombotic complications. Its safety profile was comparable to heparin lock solution. PMID- 26141308 TI - Ligand- and receptor-based docking with LiBELa. AB - Methodologies on molecular docking are constantly improving. The problem consists on finding an optimal interplay between the computational cost and a satisfactory physical description of ligand-receptor interaction. In pursuit of an advance in current methods we developed a mixed docking approach combining ligand- and receptor-based strategies in a docking engine, where tridimensional descriptors for shape and charge distribution of a reference ligand guide the initial placement of the docking molecule and an interaction energy-based global minimization follows. This hybrid docking was evaluated with soft-core and force field potentials taking into account ligand pose and scoring. Our approach was found to be competitive to a purely receptor-based dock resulting in improved logAUC values when evaluated with DUD and DUD-E. Furthermore, the smoothed potential as evaluated here, was not advantageous when ligand binding poses were compared to experimentally determined conformations. In conclusion we show that a combination of ligand- and receptor-based strategy docking with a force field energy model results in good reproduction of binding poses and enrichment of active molecules against decoys. This strategy is implemented in our tool, LiBELa, available to the scientific community. PMID- 26141307 TI - Advance care planning and end-of-life decision making in dialysis: a randomized controlled trial targeting patients and their surrogates. AB - BACKGROUND: Few trials have examined long-term outcomes of advance care planning (ACP) interventions. We examined the efficacy of an ACP intervention on preparation for end-of-life decision making for dialysis patients and surrogates and for surrogates' bereavement outcomes. STUDY DESIGN: A randomized trial compared an ACP intervention (Sharing Patient's Illness Representations to Increase Trust [SPIRIT]) to usual care alone, with blinded outcome assessments. SETTING & PARTICIPANTS: 420 participants (210 dyads of prevalent dialysis patients and their surrogates) from 20 dialysis centers. INTERVENTION: Every dyad received usual care. Those randomly assigned to SPIRIT had an in-depth ACP discussion at the center and a follow-up session at home 2 weeks later. OUTCOMES & MEASUREMENTS: PRIMARY OUTCOMES: preparation for end-of-life decision making, assessed for 12 months, included dyad congruence on goals of care at end of life, patient decisional conflict, surrogate decision-making confidence, and a composite of congruence and surrogate decision-making confidence. SECONDARY OUTCOMES: bereavement outcomes, assessed for 6 months, included anxiety, depression, and posttraumatic distress symptoms completed by surrogates after patient death. RESULTS: PRIMARY OUTCOMES: adjusting for time and baseline values, dyad congruence (OR, 1.89; 95% CI, 1.1-3.3), surrogate decision-making confidence (beta=0.13; 95% CI, 0.01-0.24), and the composite (OR, 1.82; 95% CI, 1.0-3.2) were better in SPIRIT than controls, but patient decisional conflict did not differ between groups (beta=-0.01; 95% CI, -0.12 to 0.10). SECONDARY OUTCOMES: 45 patients died during the study. Surrogates in SPIRIT had less anxiety (beta=-1.13; 95% CI, -2.23 to -0.03), depression (beta=-2.54; 95% CI, 4.34 to -0.74), and posttraumatic distress (beta=-5.75; 95% CI, -10.9 to -0.64) than controls. LIMITATIONS: Study was conducted in a single US region. CONCLUSIONS: SPIRIT was associated with improvements in dyad preparation for end of-life decision making and surrogate bereavement outcomes. PMID- 26141310 TI - Erratum. PMID- 26141309 TI - The Genetic Counseling Workplace-An Australasian Perspective. A National Study of Workplace Issues for Genetic Counselors and Associate Genetic Counselors. AB - Genetic counseling in Australasia (Australia and New Zealand) has been recognized as a profession since the 1980s and has steadily expanded over the past 20 years. The demography of major cities with metropolitan sprawl and sparsely populated rural areas has led to the establishment of 3 types of genetics units: main units in cities, metropolitan outreach, and rural outreach units. A questionnaire was developed to obtain information about the needs, resources, and day-to-day operation of the genetic counselors. The questionnaire addressed the areas of resource availability, professional development, responsibility of genetic counselors in the clinical setting, and their involvement in promotion of the service and public education. Differences observed between the 3 settings in all of these areas included large clinical loads for metropolitan outreach counselors, varying responsibilities in the clinical setting, and a lack of support and resources for rural outreach counselors. Australasian Genetic counselors were found to have a significant interest in developing mechanisms for supervision and were keenly interested in maintaining credentials and professional role development. The results of this study allows genetic counselors themselves to have a better understanding of the roles of their colleagues in the different units; they can also be used by service providers in establishing and supporting genetic counselors, and identifying inequalities and deficiencies in the different practice areas. PMID- 26141311 TI - The underused hip in ipsilaterally orthotics-dependent children. AB - BACKGROUND: The aim of this investigation is the development of primarily healthy hips in children who have required orthoses/protheses over the long term due to ipsilateral distally located deformities of the leg. These children show ipsilateral in-toeing gait and Duchenne's limping followed by a coxa valga antetorta and facultative hip decentration. A practical question is whether these hips are in danger of decompensation. An additional theoretical question is how the external shape and internal architecture changes if a primarily healthy hip is underused. METHODS: Ten children with healthy hips who are unilaterally long term orthotics/prosthetics-dependent agreed to undergo an instrumental gait analysis. The results were analyzed and correlated with clinical findings, a common activity score and planimetric radiographic data. RESULTS: The intra individual comparison revealed a number of significant changes in the hip of the deformed leg (p < 0.05). Clinically, the internal rotation was increased (15 degrees +/- 4.2 degrees ), while the external rotation was diminished (13 degrees +/- 1.3 degrees ). Radiologically, the projected caput-collum-diaphyseal angle, the lesser trochanter to articular surface distance and the head-shaft angle were increased by 11.1 degrees +/- 15.4 degrees , 5.8 +/- 4.2 mm and 11.9 degrees +/- 0.6 degrees , respectively. Both the Sharp and acetabular angles were increased, the former by 3.6 degrees +/- 0.6 degrees and the latter by 3.2 degrees +/- 0.6 degrees . Kinetic gait analysis showed increased stride length (6.8 +/- 3.7 cm), shortened stance phase (6.6 +/- 1.6 %) and reduced forces transmitted to the ground (92.2 +/- 34.3 N). The kinematic analysis showed increased hip abduction (14.0 degrees +/- 8.2 degrees ), while the pelvic obliquity was not significantly changed (0.01 degrees +/- 0.01 degrees ). CONCLUSIONS: Duchenne's limp and lack of weight-bearing stress are the decisive pathogenic factors of the underused coxa valga and acetabular dysplasia. These changes follow the mechanobiological concept of "function modifies design", which means function influences external shape and internal architecture of bones and joints. As a practical consequence we recommend that one pelvic radiograph be performed as a precaution at the end of puberty of children with these conditions. LEVEL OF EVIDENCE: Level II retrospective study. PMID- 26141312 TI - Skin Biopsy and Patient-Specific Stem Cell Lines. AB - The generation of patient-specific induced pluripotent stem (iPS) cells permits the development of next-generation patient-specific systems biology models reflecting personalized genomics profiles to better understand pathophysiology. In this chapter, we describe how to create a patient-specific iPS cell line. There are three major steps: (1) performing a skin biopsy procedure on the patient; (2) extracting human fibroblast cells from the skin biopsy tissue; and (3) reprogramming patient-specific fibroblast cells into the pluripotent stem cell stage. PMID- 26141313 TI - Computational Biology Methods for Characterization of Pluripotent Cells. AB - Pluripotent cells are a powerful tool for regenerative medicine and drug discovery. Several techniques have been developed to induce pluripotency, or to extract pluripotent cells from different tissues and biological fluids. However, the characterization of pluripotency requires tedious, expensive, time-consuming, and not always reliable wet-lab experiments; thus, an easy, standard quality control protocol of pluripotency assessment remains to be established. Here to help comes the use of high-throughput techniques, and in particular, the employment of gene expression microarrays, which has become a complementary technique for cellular characterization. Research has shown that the transcriptomics comparison with an Embryonic Stem Cell (ESC) of reference is a good approach to assess the pluripotency. Under the premise that the best protocol is a computer software source code, here I propose and explain line by line a software protocol coded in R-Bioconductor for pluripotency assessment based on the comparison of transcriptomics data of pluripotent cells with an ESC of reference. I provide advice for experimental design, warning about possible pitfalls, and guides for results interpretation. PMID- 26141314 TI - Surgical resection of peripheral odontogenic fibromas in African pygmy hedgehog (Atelerix albiventris): a case study. AB - BACKGROUND: Neoplastic lesions of the mammary gland, lymph nodes, or oral cavity in African pygmy hedgehogs (Atelerix albiventris) are common in captive animals. Chemotherapy and radiotherapy protocols have not yet been established for the African pygmy hedgehog. Thus, surgical resection is the current treatment of choice in this species. CASE PRESENTATION: A 5-year-old male African pygmy hedgehog showed multiple erythematous, round small tumors located in the oral cavity, on both sides of maxilla. The treatment of choice was surgical resection of tumors using a surgical knife under general anesthesia. Excised neoplastic lesions were diagnosed as peripheral odontogenic fibroma by histopathology. Six months after surgery relapse of tumors in the oral cavity was not observed. CONCLUSIONS: The treatment adopted in this case report is safe for the patient and provides the best solution for mild proliferative lesions of the oral cavity. To our knowledge this is the first report of surgical resection of oral tumors (peripheral odontogenic fibroma) in the African pygmy hedgehog. PMID- 26141315 TI - Restricting access to florbetapir: Medicare coverage criteria for diagnostics and drugs are inconsistent. PMID- 26141316 TI - The "Circular" Problems of Calculating Risk: Dealing with Consanguinity. AB - An ongoing problem in the genetics clinic is the calculation of inbreeding coefficients and recurrence risks for complex pedigrees, particularly when multiple "loops" are present. Although the Human Genome Project promises information about more of our genes in the foreseeable future, the actual assignment of disease status to specific loci will continue at a slower pace, so that accurate risk calculations are needed. In the past few months several families with consanguinity were referred to us to confirm the calculations performed by the genetic counselor, and we became aware of some confusion in the field. We present here both (a) a clarification of definitions and concepts and (b) a review of how to perform the calculations, for several quantities (coefficient of relationship, coefficient of inbreeding, coefficient of kinship, and recurrence risk), in complex pedigrees. We discuss the availability of computer algorithms to assist in these calculations, and we encourage counselors to call on a reliable computer program for any but the simplest cases. At the same time, we reiterate our belief that computer algorithms do not relieve the counselor of the responsibility of knowing what to calculate and when. PMID- 26141317 TI - To Use or Not to Use: The Prenatal Genetic Technology/Worry Conundrum. AB - We conducted an exploratory, qualitative study investigating the factors influencing the use of genetic counseling and prenatal genetic testing for two groups: pregnant women 35 years of age and over (AMA) at the time of delivery and pregnant women with an abnormal maternal serum triple screen (MSAFP3). The convenience sample consisted of 25 semistructured interviews of women/couples and 50 observations of genetic counseling sessions. Worry turned out to be the most important variable influencing decision making about prenatal genetic testing and was greater in the MSAFP3 group than in the AMA group. The women in the AMA group appeared to assign the risk of having a child with Down syndrome to their age category rather than to themselves individually, whereas, the risk perception for women with an abnormal MSAFP3 appeared to have shifted from a general population risk for pregnant women to an individual, personal risk. There was a general lack of understanding and also more misinformation about the MSAFP3 screen compared to amniocentesis. Women in both groups were torn between fear of an invasive test and worry about the health of their fetus for the rest of their pregnancy if they did not undergo amniocentesis. PMID- 26141318 TI - Patient Motivation, Satisfaction, and Coping in Genetic Counseling and Testing for BRCA1 and BRCA2. AB - Women with a strong family history of breast and/or ovarian cancer can now have genetic testing, that may identify mutations associated with increased cancer predisposition. Within the context of a clinical trial evaluating printed educational materials, we examined motivation, satisfaction, coping, and perceptions of genetic counseling and testing among 159 women who underwent pretest counseling and made a testing decision. Ninety-six percent of the participants elected to have BRCA1/2 testing. When making a decision about genetic testing, study participants were concerned less about the potential negative effects that could result from testing than the potential benefits. After counseling, participants said that they felt better able to make decisions that were right for them and that their questions and concerns were adequately addressed during the session. Ninety-five percent of the women were satisfied with their test decision. Participants used a range of strategies to cope with thoughts and feelings about cancer and/or genetic testing immediately following test decision. Results suggest that the genetic counseling session helped women make decisions about testing for BRCA1 and BRCA2, even in the setting of a trial in which all women also received detailed educational materials. Further, the results indicate that future research focusing on perceptions of risks and benefits of testing and of coping strategies immediately following test decision may be warranted. PMID- 26141319 TI - The Process of Family Reconstruction after DNA Testing for Huntington Disease. AB - The needs of families to reconstruct their relationships in response to the DNA testing for Huntington disease of one or more of their asymptomatic members are presented. Data were collected from family interviews with 18 families, and from their responses on a post interview questionnaire. Findings are that families need to (a) address "unfinished business" associated with the decision for testing; (b) bring family members, peripheral in the decision for testing, into the loop; (c) reorganize patterns of communication and roles altered by the testing and heal ruptures in family membership; and (d) revise family stories about illness to provide a meaning for HD and explain the test results in a way that leaves them with a sense of mastery. Findings suggest that families should be more involved in the initial decision for testing of a member and that protocols should be established to provide help for their ongoing adjustment. PMID- 26141321 TI - Genetic Library. PMID- 26141322 TI - Letter to the Editor: Emotional Rescue. PMID- 26141320 TI - Who Is at Risk for Psychological Distress in Genetic Testing Programs for Hereditary Cancer Disorders? AB - Presymptomatic identification of disease gene carriers is becoming an increasingly common part of the clinical management of hereditary cancer disorders. With an expected increase in the number of requests for DNA testing and the limited resources for counseling, the amount of time genetic counselors are able to spend with test candidates will decrease. It is therefore important for counselors to identify persons at risk for psychological distress. Based on a review of experiences with Huntington disease and cancer patients, we describe factors likely to evoke distress in genetic cancer candidates. We also discuss the sometimes widely different ways that test candidates and their partners respond to genetic testing. By exploring risk factors for distress in relevant domains of the research, we can offer counselors guidelines for determining who may need extra counseling. PMID- 26141323 TI - Instructions to Contributors. PMID- 26141324 TI - A surface wipe sampling and LC-MS/MS method for the simultaneous detection of six antineoplastic drugs commonly handled by healthcare workers. AB - An effective wipe sampling and LC-MS/MS method was developed to simultaneously analyze six commonly administered antineoplastic drugs in stainless steel surface. The analyzed drugs were methotrexate, paclitaxel, cyclophosphamide, 5 fluorouracil, vincristine, and oxaliplatin, a frequently prepared antineoplastic drug that has not been included among any of the published simultaneous detection methods. The established method was used to evaluate the recoveries of antineoplastic drugs on brand new and worn stainless steel surfaces by wiping the plates with a Whatman filter paper wetted with 0.5 mL of water/methanol (20:80) with 0.1% formic acid followed by LC-MS/MS before desorbing the filter with a water/methanol (50:50) solution. A significant decrease in the recovery of all evaluated drugs was found when worn plates were used. Additionally, the inter personnel variability on drug recoveries during wiping procedures was evaluated. Significantly higher recoveries were achieved by the personnel with more training and experience versus personnel without prior experience. Finally, a laboratory stability test was developed to assess the degradation of the antineoplastic drugs during replicated shipping conditions. With the exception of vincristine sulfate which exhibited a significant (p < 0.05) degradation after 48 h, all evaluated drugs were stable during the first 24-48 h. However, after 144 h, an increase in the degradation of all evaluated drugs was observed, with oxaliplatin and 5-fluorouracil exhibiting the most degradation. PMID- 26141326 TI - Introduction to the Symposium on Neoplastic Hematology and Medical Oncology. PMID- 26141325 TI - Pacemaker replacement in nonagenarians: Procedural safety and long-term follow up. AB - BACKGROUND: The rate of pacemaker implantation is rising. Given that the life expectancy of the population is projected to increase, a large number of elderly patients are likely to be implanted in the future. As pacemaker batteries can last for 8-10years, an increasing number of pacemaker recipients will require replacement of their devices when they become nonagenarians. AIMS: To analyse the short- and long-term outcomes after device replacement in nonagenarians. METHODS: Patients aged>=90years referred to a tertiary centre for pacemaker replacement from January 2004 to July 2014 were included retrospectively. Clinical follow-up data were obtained from clinical visits or telephone interviews with patients or their families. The primary clinical endpoint was total mortality. Secondary endpoints included early and delayed procedure-related complications and predictive risk factors for total mortality. RESULTS: Sixty-two patients were included (mean age 93.3+/-2.9years at time of pacemaker replacement). Mean procedure duration was 35.7+/-17.2minutes. Mean hospital stay was 2.2+/-1.1days. One patient died from a perioperative complication. Thirty-seven patients (59.7%) died during a median follow-up of 22.1months (interquartile range, 11.8 39.8months). Survival rates were 84.2% (95% confidence interval [CI] 71.8-91.5%) at 1year, 66.9% (95% CI 51.8-78.2%) at 2years and 22.7% (95% CI 10.6-37.7%) at 5years. Atrial fibrillation (hazard ratio 2.47, 95% CI 1.1-5.6) and non physiological pacing (i.e. VVI pacing in patients in sinus rhythm) (hazard ratio 2.20, 95% CI 1.0-4.9) were predictors of mortality. CONCLUSIONS: Pacemaker replacement in nonagenarians is a safe and straightforward procedure. These data suggest that procedures can be performed securely in this old and frail population, with patients living for a median of 30months afterwards. PMID- 26141327 TI - Incidence and Risk Factors for Progression From Short-term to Episodic or Long term Opioid Prescribing: A Population-Based Study. AB - OBJECTIVES: To determine what proportion of a geographically defined population who receive new opioid prescriptions progresses to episodic or long-term patterns of opioid prescribing and to explore the clinical characteristics associated with patterns of opioid prescribing. PATIENTS AND METHODS: Population-based drug prescription records for the population of Olmsted County between January 1 and December 31, 2009, were obtained using the Rochester Epidemiology Project medical records linkage system (N=142,377). All medical records were reviewed for a random sample of 293 patients who had a new ("incident") prescription for an opioid analgesic in 2009. Patients were followed through their medical records for 1 year after their initial prescription date, with patterns of opioid prescribing categorized as short-term, episodic, or long-term. RESULTS: Overall, 293 patients received 515 new opioid prescriptions in 2009. Of these, 61 (21%) progressed to an episodic prescribing pattern and 19 (6%) progressed to a long term prescribing pattern. In multivariable logistic regression analyses, substance abuse was significantly associated (P<.001) with a long-term opioid prescribing pattern as compared with an short-term opioid prescribing pattern. Past or current nicotine use (P=.03) and substance abuse (P=.04) were significantly associated with an episodic or long-term prescribing pattern as compared with a short-term prescribing pattern. CONCLUSION: Knowledge of the clinical characteristics associated with the progression of a short-term to an episodic or long-term opioid prescribing pattern could aid in the identification of at-risk patients and provide the basis for developing targeted clinical interventions. PMID- 26141328 TI - Long-term Outcomes and Prognostic Factors for Patients Requiring Renal Replacement Therapy After Cardiac Surgery. AB - OBJECTIVE: To examine long-term outcomes, including all-cause mortality, and the likelihood and timing of renal recovery among patients requiring renal replacement therapy (RRT) for acute kidney injury after cardiac surgery. PATIENTS AND METHODS: This is a single-center, historical, matched cohort study of post cardiac surgery patients who required RRT from January 1, 2007, through December 31, 2012. We matched each case with 2 controls, each of whom did not require RRT after cardiac surgery, for age, sex, and type of surgery. The patients were followed up for 1 year after the start of RRT. The main outcomes were all-cause mortality in all patients and rate of renal function recovery in patients who required RRT. RESULTS: A total of 202 patients met the inclusion criteria. The unadjusted all-cause mortality among patients requiring RRT was 64% at 1 year vs 8% for matched controls. In multivariate analysis, the hazard ratio for all-cause mortality was 12.59 (95% CI, 8.24-19.68) for cases vs controls. Increased 1-year all-cause mortality was independently associated with increased age, a history of congestive heart failure, lower preoperative creatinine level, longer interval between surgery and starting RRT, and the need for mechanical ventilation or an intra-aortic balloon pump at the time of RRT. Renal recovery occurred in 34% of cases by 90 days and in 39% by 1 year. Of those who recovered renal function, 87% were within 90 days. Only 8 (4%) of the 186 patients were alive and continued to receive RRT at 1 year. CONCLUSIONS: The need for RRT after cardiac surgery is an independent risk factor for mortality. In the case of survival, the chance of renal recovery is reasonable. PMID- 26141329 TI - Incidence of Infective Endocarditis Due to Viridans Group Streptococci Before and After the 2007 American Heart Association's Prevention Guidelines: An Extended Evaluation of the Olmsted County, Minnesota, Population and Nationwide Inpatient Sample. AB - OBJECTIVE: To determine whether the incidence of infective endocarditis (IE) due to viridans group streptococci (VGS) increased after the publication of the 2007 American Heart Association (AHA) IE prevention guidelines. PATIENTS AND METHODS: We performed a population-based survey of all adults (18 years and older) residing in Olmsted County, Minnesota, from January 1, 1999, through December 31, 2013, to identify definite or possible cases of VGS-IE using the Rochester Epidemiology Project. The National (Nationwide) Inpatient Sample hospital discharge database was examined to determine the number of VGS-IE cases in the United States between 2000 and 2011. RESULTS: Rates of incidence (per 100,000 person-years) during the intervals of 1999-2002, 2003-2006, 2007-2010, and 2011 2013 were 3.6 (95% CI, 1.3-5.9), 2.7 (95% CI, 0.9-4.4), 0.7 (95% CI, 0.0-1.6), and 1.5 (95% CI, 0.2-2.9), respectively, reflecting an overall significant decrease (P=.03 from Poisson regression). Likewise, nationwide estimates of hospital discharges with a VGS-IE diagnosis trended downward during 2000-2011, with a mean number per year of 15,853 and 16,157 for 2000-2003 and 2004-2007, respectively, decreasing to 14,231 in 2008-2011 (P=.05 from linear regression using weighted least squares method). CONCLUSION: Despite major reductions in the number of indications for antibiotic prophylaxis for invasive dental procedures espoused by the 2007 AHA IE prevention guidelines, both local and national data indicate that the incidence of VGS-IE has not increased. PMID- 26141330 TI - Changes in the Relationships Between Body Mass Index and Health Outcomes Across Middle Age and Older Adulthood. AB - OBJECTIVE: To examine patterns of the incidence of diabetes, hypertension, and mortality by single units of body mass index (BMI) and 5-year age groups using longitudinal data from middle-aged and older women. PATIENTS AND METHODS: Middle aged (born between 1946 and 1951; N = 13,715) and older (born between 1921 and 1926; N = 12,432) participants in the Australian Longitudinal Study on Women's Health completed surveys in 1996 and at approximately 3-year intervals thereafter until 2011. Proportions of women with diabetes, hypertension, and mortality over 3-year intervals were estimated for each unit of BMI and 5-year age group (45 to < 50, 50 to < 55, 55 to < 60, 70 to < 75, 75 to < 80, and 80 to < 85 years) using generalized additive modeling with adjustment for time-varying covariates. RESULTS: Three-year incidence of diabetes (1.2%-3.6%), hypertension (5.2%-17.8%), and death (0.4%-9.5%) increased with age. For both diabetes and hypertension, the associations with BMI were curvilinear in middle-aged women and became almost linear in older women. With increasing age, the slope became steeper, and the increase started at lower BMI values. For hypertension, there was a marked increase in intercept from 75 years onward. In contrast, mortality risks were highest for low BMI (<= 20) in all age groups. A clear U-shaped curve was observed only in the oldest age group. CONCLUSION: The shapes of the relationships between BMI and incidence of diabetes, hypertension, and mortality change with age, suggesting that weight management interventions should be tailored for different age groups. PMID- 26141331 TI - Diagnostic Approach to the Complexity of IgG4-Related Disease. AB - IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4 RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related. PMID- 26141332 TI - Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management. AB - Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. PMID- 26141333 TI - 59-Year-Old Man With Aphasia and Proteinuria. PMID- 26141334 TI - Opioid Analgesics. AB - Chronic pain is an international health issue of immense importance that is influenced by both physical and psychological factors. Opioids are useful in treating chronic pain but have accompanying complications. It is important for clinicians to understand the basics of opioid pharmacology, the benefits and adverse effects of opioids, and related problematic issues of tolerance, dependence, and opioid-induced hyperalgesia. In this article, the role of psychiatric comorbidity and the use of validated assessment tools to identify individuals who are at the greatest risk for opioid misuse are discussed. Additionally, interventional treatment strategies for patients with chronic pain who are at risk for opioid misuse are presented. Specific behavioral interventions designed to improve adherence with prescription opioids among persons treated for chronic pain, such as frequent monitoring, periodic urine screens, opioid therapy agreements, opioid checklists, and motivational counseling, are also reviewed. Use of state-sponsored prescription drug monitoring programs is also encouraged. Areas requiring additional investigation are identified, and the future role of abuse-deterrent opioids and innovative technology in addressing issues of opioid therapy and pain are presented. PMID- 26141335 TI - Myelodysplastic Syndromes: Diagnosis and Treatment. AB - In the past few years, new biological insights into the myelodysplastic syndromes (MDS) resulting from molecular genetic analysis have improved pathologic understanding, but treatment advances have not kept pace. More than 40 genes are now known to be recurrently mutated in MDS. However, because most of these genes encode spliceosome components, chromatic remodeling factors, epigenetic pattern modulators, or transcription factors rather than more easily inhibited activated tyrosine kinases, there are as of yet few narrowly targeted therapies available for MDS. Three drugs--azacitidine, decitabine, and lenalidomide--were approved by the US Food and Drug Administration for MDS indications a decade ago, and these agents can improve hematopoiesis, delay disease progression, and improve survival and quality of life for a subset of patients. However, only a few patients with MDS respond to these agents, and their benefit is temporary. The only potentially curative therapy for MDS is allogeneic hematopoietic stem cell transplant, but owing to the advanced age of many patients with MDS and the frequency of serious comorbid conditions, less than 10% of patients currently undergo stem cell transplant. This narrative review summarizes the current understanding of MDS and treatment options for these challenging disorders. PMID- 26141336 TI - Fructose as a Driver of Diabetes: An Incomplete View of the Evidence. PMID- 26141337 TI - In reply--Fructose as a Driver of Diabetes: An Incomplete View of the Evidence. PMID- 26141338 TI - In reply--Cutaneous and Uterine Leiomyomas. PMID- 26141339 TI - Cutaneous and Uterine Leiomyomas. PMID- 26141340 TI - Asteroid Hyalosis. PMID- 26141341 TI - 72-Year-Old Man With Fever and Malaise. PMID- 26141343 TI - Complete pathological response of unresectable liver metastases from colorectal cancer after trans-arterial chemoembolization with drug-eluting beads loaded with irinotecan (DEBIRI) and concomitant systemic FOLFOX: A case report from the FFCD 1201 trial. AB - INTRODUCTION: Most liver metastases from colorectal cancer (CRC) are unresectable at diagnosis. Systemic chemotherapy allows secondary surgical resection in 10 to 20% of patients. Hepatic intra-arterial treatments could enhance response and resection rate. We therefore designed a prospective phase II trial testing the transarterial chemoembolization (TACE) using drug-eluting beads loaded with irinotecan (DEBIRI) with concomitant systemic FOLFOX regimen, the FFCD 1201 trial, in patients with liver limited metastatic CRC. CASE REPORT: A 48-year old patient was operated from an occlusive sigmoid adenocarcinoma. Magnetic resonance imaging showed 6 bilobar liver metastasis. The patient was considered as non eligible for surgery initially. Patient was included in the FFCD 1201 trial and received 5 cycles of FOLFOX and 2 sessions of DEBIRI, with a quite good tolerability. Post-treatment evaluation showed a partial response and sufficient tumor shrinkage to make liver metastasis resectable. Right hepatectomy associated with wedge resection in the left liver was performed and pathological findings showed a complete pathological response (CPR). CONCLUSION: Combination of DEBIRI with FOLFOX could increase tumor shrinkage leading to secondary resection of liver metastases from CRC. This combination may also, as shown here for the first time in a patient with unresectable LM, induce CPR of all LM, known to be associated with better outcome. Our case also emphasizes the difficulty to morphologically assess pathological response and the need for new tool to better select patients who should be resected. Further results of the FFCD 1201 trial will bring more information on this new combination therapy. PMID- 26141344 TI - Colloid release and clogging in porous media: Effects of solution ionic strength and flow velocity. AB - The release and retention of in-situ colloids in aquifers play an important role in the sustainable operation of managed aquifer recharge (MAR) schemes. The processes of colloid release, retention, and associated permeability changes in consolidated aquifer sediments were studied by displacing native groundwater with reverse osmosis-treated (RO) water at various flow velocities. Significant amounts of colloid release occurred when: (i) the native groundwater was displaced by RO-water with a low ionic strength (IS), and (ii) the flow velocity was increased in a stepwise manner. The amount of colloid release and associated permeability reduction upon RO-water injection depended on the initial clay content of the core. The concentration of released colloids was relatively low and the permeability reduction was negligible for the core sample with a low clay content of about 1.3%. In contrast, core samples with about 6 and 7.5% clay content exhibited: (i) close to two orders of magnitude increase in effluent colloid concentration and (ii) more than 65% permeability reduction. Incremental improvement in the core permeability was achieved when the flow velocity increased, whereas a short flow interruption provided a considerable increase in the core permeability. This dependence of colloid release and permeability changes on flow velocity and colloid concentration was consistent with colloid retention and release at pore constrictions due to the mechanism of hydrodynamic bridging. A mathematical model was formulated to describe the processes of colloid release, transport, retention at pore constrictions, and subsequent permeability changes. Our experimental and modeling results indicated that only a small fraction of the in-situ colloids was released for any given change in the IS or flow velocity. Comparison of the fitted and experimentally measured effluent colloid concentrations and associated changes in the core permeability showed good agreement, indicating that the essential physics were accurately captured by the model. PMID- 26141345 TI - Electro-responsive macroporous polypyrrole scaffolds for triggered dexamethasone delivery. AB - Corticosteroids such as dexamethasone are first line ophthalmic treatment for non infectious posterior uveitis. Corticosteroids are often administered via intravitreal injection to treat this condition with frequent injections associated with poor treatment adherence and complications such as endophthalmitis. Current ocular implants provide sustained corticosteroid release at predetermined rates and lack the ability for dose individualisation. This study describes the successful fabrication of electrically responsive macroporous polypyrrole (PPy) thin films, and their subsequent application to triggered dexamethasone release. Colloidal crystal films composed of 370nm polymethylmethacrylate colloids were first deposited on ITO coated glass substrates, and subsequently used as sacrificial templates for the fabrication of high surface area, 3-dimensionally ordered macroporous PPy inverse opal (PPy IO) thin films. SEM, UV-Vis reflectance and cyclic voltammetry measurements established that the redox state of the PPy IO films could be controlled via electrical stimulation, which in turn influences both porosity and optical properties of the films. Incorporation of the anti-inflammatory corticosteroid, dexamethasone phosphate (DexP), in the PPy IO films during their fabrication resulted in an effective delivery platform for triggered DexP release. A sustained release profile was observed for the PPy IO-DexP films, bursts of release could be triggered by electrical stimulation. The amount of DexP released from the PPy IO-DexP films was significantly higher than that released from the conventional non-porous PPy-DexP films of comparable mass. Results suggest that electrically responsive PPy IO structures are highly suitable for on-demand drug delivery applications. This technology may enable physicians to fine-tune the required dose according to disease state and patients' needs to enhance the safety and efficacy of corticosteroid treatment. PMID- 26141347 TI - Rape and Posttraumatic Stress Disorder (PTSD): Examining the Mediating Role of Explicit Sex-Power Beliefs for Men Versus Women. AB - Many rape survivors exhibit symptoms of post-traumatic stress disorder (PTSD), and recent literature suggests survivors' beliefs about sex and control may affect PTSD symptoms. The present study examined beliefs about sex and power as potential mediators of the relationship between rape and PTSD symptoms for men versus women. Participants ( N = 782) reported lifetime history of rape, current PTSD symptoms, and beliefs about sex and power. Women reported higher levels of lifetime history of rape than men (19.7% for women; 9.7% for men). While rape history predicted PTSD symptoms for both genders, beliefs about sex and power were shown to be a significant partial mediator of this relationship for men, but not for women. Results extend the literature on rape and PTSD by suggesting that survivors' beliefs about sex and power are connected and can affect their PTSD symptoms. Additionally, results illustrate how sexual violence against men may reaffirm male gender roles that entail power and aggression, and ultimately affect trauma recovery. PMID- 26141346 TI - Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol co-PEI)-mediated delivery of osteopontin siRNA. AB - Small interfering RNA (siRNA)-mediated gene silencing represents a promising strategy for treating diseases such as cancer; however, specific gene silencing requires an effective delivery system to overcome the instability and low transfection efficiency of siRNAs. To address this issue, a polysorbitol-based transporter (PSOT) was prepared by low molecular weight branched polyethylenimine (bPEI) crosslinked with sorbitol diacrylate (SDA). Osteopontin (OPN) gene, which is highly associated with non-small cell lung cancer (NSCLC) was targeted by siRNA therapy using siRNA targeting OPN (siOPN). Characterization study confirmed that PSOT formed compact complexes with siOPN and protected siOPN against degradation by RNase. PSOT/siOPN complexes demonstrated low cytotoxicity and enhanced transfection efficiency in vitro, suggesting that this carrier may be suitable for gene silencing. In the A549 and H460 lung cancer cell lines, PSOT/siOPN complexes demonstrated significant silencing efficiency at both RNA and protein levels. To study in vivo tumor growth suppression, two lung cancer cell-xenograft mouse models were prepared and PSOT/siOPN complexes were delivered into the mice through intravenous injection. The siOPN-treated groups demonstrated significantly reduced OPN expression at both the RNA and protein levels as well as suppression of tumor volume and weight. Taken together, siOPN delivery using PSOT may present an effective and novel therapeutic system for lung cancer treatment. PMID- 26141348 TI - Military Versus Civilian Murder-Suicide. AB - Previous studies have implicated significant differences between military members and civilians with regard to violent behavior, including suicide, domestic violence, and harm to others, but none have examined military murder-suicide. This study sought to determine whether there were meaningful differences between military and civilian murder-suicide perpetrators. Using data from the Center for Disease Control's (CDC) National Violent Death Reporting System (NVDRS), military ( n = 259) and civilian ( n = 259) murder-suicide perpetrators were compared on a number of demographic, psychological, and contextual factors using chi-square analyses. Logistic regression was used to determine which variables predicted membership to the military or civilian perpetrator groups. Military murder suicide perpetrators were more likely to be older, have physical health problems, be currently or formerly married, less likely to abuse substances, and to exhibit significantly different motives than civilian perpetrators. Logistic regression revealed that membership to the military, rather than the civilian, perpetrator group was predicted by age, physical health problems, and declining heath motive reflecting the significance of a more than 15-year difference in mean age between the two groups. Findings point to the need to tailor suicide risk assessments to include questions specific to murder-suicide, to assess attitudes toward murder suicide, and to the importance of assessing suicide and violence risk in older adult military populations. PMID- 26141349 TI - Cognitive and Affective Empathy, Personal Belief in a Just World, and Bullying Among Offenders. AB - Bullying extracts a heavy toll on offenders and prison staff alike. Studying what factors may affect bullying is extremely important as this may help to minimize bullying in prison. Although there is research on the relationship between lack of empathy and positive attitude toward bullying, previous research has overlooked that age may influence this relationship. In fact, previous research has shown that there are changes in empathy across the life span. Therefore, we examined whether having a positive attitude toward bullying in offenders was predicted by age, mediated by cognitive/affective empathy. Another important factor in the prediction of positive attitudes toward bullying may be the belief in a just world, as having a weak belief is related to more aggressive outbursts. Given that there is scarce research in the topic, we examined the relationship between having a positive attitude toward bullying and personal belief in a just world. To that aim, 123 sentenced adult male prisoners, selected from a Category C prison in the United Kingdom completed different questionnaires to assess their levels of cognitive and affective empathy, positive attitude toward bullying, and personal belief in a just world. As expected, age predicted a positive attitude toward bullying, mediated by affective empathy. However, we did not find a positive relationship between a positive attitude toward bullying and a personal belief in a just world. The results are discussed in terms of their application in possible intervention programs. PMID- 26141350 TI - Developing an Understanding of Victims and Violent Offenders: The Impact of Fostering Empathy. AB - This study explores the consequences of fostering empathy-for both victims and perpetrators-after large-scale violent events. Participants ( N = 834) read a description of a school shooting and were randomly assigned to one of six conditions revealing varying amounts of background information about the victim and the perpetrator of violence. The impact of empathy on reactions toward the victim and perpetrator were then assessed. Empathy for the perpetrator could be fostered with increased information about his background, resulting in recommendations of increased leniency. Fostering empathy for the victim promoted positive community responses, including increased intentions to engage in helping behavior and make charitable donations. The degree to which participants could make sense of the violent event was also associated with decreases in blame and anger toward the perpetrator. Potential implications of the findings for news media and community coping strategies are explored. PMID- 26141351 TI - The Relationship Between Violence and Psychological Distress Among Men and Women: Do Sense of Mastery and Social Support Matter? AB - The aims of this study were to examine associations between reported exposure to psychological and physical violence and psychological distress (PD) among men and women, and to explore the possible mediating or moderating roles of sense of mastery and social support. We used data from the nationally representative Norwegian Health and Level of Living Survey in 2005 and 2012 (Weighted N = 19,386). PD was measured with the Hopkins Symptom Checklist-25, using the subscales for anxiety and depression separately and in combination. Analyses were conducted using hierarchical logistic regression with complex sample adjustment. Altogether, 3.8% of men and 5.4% of women reported psychological violence during the last 12 months, while 2.3% and 1.6% reported physical violence, respectively. Both forms of violence were associated with excess risk of comorbid anxiety and depressive symptoms above clinical cut-point (CAD) in men and women alike, and CAD occurred more frequently than anxiety or depressive problems separately. Sense of mastery, but not social support, partly mediated the association between both forms of violence and CAD in men, whereas both partly mediated the association between psychological violence and CAD in women. No moderator role was indicated. Overall, the results provide evidence for excess risk of PD, particularly CAD, in men and women reporting exposure to violence. Sense of mastery and to a lesser degree social support were shown to constitute significant mediators, underscoring the importance of systems for strengthening coping strategies and social support among violence victims, such as psychological and practical support by the health services. PMID- 26141352 TI - Mid-term results of a less-invasive locking plate fixation method for proximal humeral fractures: a prospective observational study. AB - BACKGROUND: The optimal treatment for proximal humeral fractures remains under debate. In this article, we report the mid-term results of patients who underwent the less-invasive implantation of a polyaxial locking plate for displaced proximal humeral fractures. METHODS: This study included patients who were treated with a polyaxial locking plate via an anterolateral deltoid split approach from May 2008 to December 2011. We evaluated outcome parameters after a minimum follow-up period of 2.5 years (median 4.5 years, follow-up rate 62 %) including the age- and gender-dependent Constant score, the activities of daily living score, and the visual analog scale for both pain and subjective shoulder function. RESULTS: Of the 140 patients who underwent surgery, 114 were included in the follow-up and 71 completed the questionnaire. Fifteen patients (21 %) exhibited 2-fragment fractures, and 56 patients (79 %) exhibited 3- and 4-part fractures. The Constant score improved significantly (4.5 years: 70 +/- 21, p < 0.001) between the first two follow-ups (6 weeks: 35 +/- 14, 6 months: 56 +/- 18, p < 0.001), and also between 6 months and 4.5 years post-surgery. At the final follow-up, the activities of daily living score had not reached pre-fracture levels (before trauma: 27 +/- 5, 4.5 years: 20 +/- 8, p < 0.001). A multivariate analysis showed that age has a more significant influence on the final outcome than fracture morphology or gender. CONCLUSION: Although the less-invasive surgical procedure is a feasible treatment option in proximal humeral fractures with acceptable complications and considerable improvement during the first six months, a lengthy recovery time is required. The majority of our patients did not become pain-free or reach pre-fracture activity levels. PMID- 26141353 TI - Endoscopic Endonasal Extended Approaches for the Management of Large Pituitary Adenomas. AB - The management of giant and large pituitary adenomas with wide intracranial extension or infrasellar involvement of nasal and paranasal cavities is a big challenge for neurosurgeons and the best surgical approach indications are still controversial. Endoscopic extended endonasal approaches have been proposed as a new surgical technique for the treatment of such selected pituitary adenomas. Surgical series coming from many centers all around the world are flourishing and results in terms of outcomes and complications seem encouraging. This technique could be considered a valid alternative to the transcranial route for the management of giant and large pituitary adenomas. PMID- 26141354 TI - Endoscopic Endonasal Repair of Spontaneous and Traumatic Cerebrospinal Fluid Rhinorrhea: A Review and Local Experience. AB - This article presents an overview of endoscopic endonasal repair of cerebrospinal fluid (CSF) rhinorrhea. In recent years, endoscopic repair has become the standard of care for managing this condition, because it gradually replaces the traditional open transcranial approach. Discussion includes the etiologic classification of CSF rhinorrhea, management paradigm for each category, diagnosis algorithm, comprehensive description of the surgical technique, and an updated review of the literature regarding the safety and efficacy of this procedure. In addition, the authors present their experience, including 2 surgical videos demonstrating endoscopic repair of CSF rhinorrhea in 2 distinct clinical scenarios. PMID- 26141355 TI - Endoscopic Endonasal Approach for Removal of Tuberculum Sellae Meningiomas. AB - Tuberculum sellae meningiomas are challenging lesions; their critical location and often insidious growth rate enables significant distortion of the superjacent optic apparatus before the patient notices any visual impairment. This article describes the technical nuances, selection criteria and complication avoidance strategies for the endonasal resection of tuberculum sellae meningiomas. A stepwise description of the surgical technique is presented; indications, adjuvant technologies, pitfalls and the relevant anatomy are also reviewed. Tuberculum sellae meningiomas may be safely and effectively resected through the endonasal route; invasion of the optic canals does not represent a limitation. PMID- 26141356 TI - Endoscopic Endonasal Approach for Craniopharyngiomas. AB - The endoscopic endonasal approach for craniopharyngiomas is increasingly used as an alternative to microsurgical transsphenoidal or transcranial approaches. It is a step forward in treatment, providing improved resection rates and better visual outcome. Especially in retrochiasmatic tumors, this approach provides better lesion access and reduces the degree of manipulations of the optic apparatus. The panoramic view offered by endoscopy and the use of angulated optics allows the removal of lesions extending far into the third ventricle avoiding microsurgical brain splitting. Intensive training is required to perform this surgery. This article summarizes the surgical technique, outcome, and complications. PMID- 26141357 TI - Endoscopic Endonasal Approach for Olfactory Groove Meningiomas: Operative Technique and Nuances. AB - Olfactory groove meningiomas represent approximately 10% of all intracranial meningiomas. Because these tumors originate at the ventral skull base, the endonasal route provides direct access to the tumor blood supply for early devascularization and removal of the underlying hyperostotic bone at the cranial base. In carefully selected patients, these tumors can be totally removed without additional brain retraction or manipulation. In this report, we describe the surgical technique and operative nuances for removal of olfactory groove meningiomas using the endoscopic endonasal approach, and also discuss the indications, limitations, complication avoidance and management, and postoperative care. PMID- 26141358 TI - Endonasal Endoscopic Management of Parasellar and Cavernous Sinus Meningiomas. AB - The management of cavernous sinus and invasive parasellar meningiomas often requires a multimodality treatment approach. Early attempts at complete or near complete removal of parasellar meningiomas involving the cavernous sinus, Meckel cave, clivus, and sella using anterolateral or lateral skull base approaches were typically unsuccessful and yielded high rates of new cranial neuropathy and other complications. This article presents a strategy of endonasal endoscopic parasellar skull base bony decompression and limited tumor removal followed by stereotactic radiotherapy, stereotactic radiosurgery, or observation. Patient selection, technical nuances, potential complications, and initial outcomes in a small series of patients are discussed. PMID- 26141359 TI - Surgical Techniques for Sinonasal Malignancies. AB - Sinonasal malignancies are a rare subset of malignancies of the upper aerodigestive tract which had been traditionally approached via open techniques. This article primarily addresses a paradigm shift in endoscopic endonasal oncological resection utilizing principles of tumor disassembly and negative margins. The surgical steps to these endoscopic techniques are detailed, emphasizing principles of sound oncological resection. PMID- 26141360 TI - Endoscopic Endonasal Approach to Ventral Posterior Fossa Meningiomas: From Case Selection to Surgical Management. AB - Clival, petroclival, and foramen magnum meningiomas are challenging lesions to manage independently of the selected surgical approach. The expanded endoscopic endonasal approach (EEA) provided a safe alternative on the armamentarium of skull base approaches. There is a paucity of literature regarding endoscopic management of meningiomas because of certain limiting factors, including rarity of the pathologic condition, technical challenges, expertise of the surgical team, and available resources. The surgical technique, possible complications, and postoperative care are described in detail. This article highlights the important aspects in choosing this surgical approach and managing ventral posterior fossa meningiomas through the EEA. PMID- 26141361 TI - Endoscopic Endonasal Odontoidectomy. AB - Odontoidectomy is the treatment of choice for irreducible ventral cervical medullary compression. The endonasal endoscopic approach is an innovative approach for odontoidectomy. The aim of this article is to identify in which conditions this approach is indicated, discussing variants of the technique for selected cases of craniovertebral malformation with platybasia. We believe that the technical difficulties of this approach are balanced by the advantages for patients. Some conditions related to the patient and to the anatomy of the craniovertebral junction may favor adoption of the endoscopic endonasal approach, which should be considered complementary and not alternative to standard approaches. PMID- 26141362 TI - Chordomas: A Review. AB - Chordomas (CHs) are tumors with benign histopathology but exhibit aggressive clinical behavior with invasive and metastatic potential. CHs are challenging tumors to treat, and there are still many questions especially about their optimum treatment. Radical resection at first presentation should be applied on all CHs. Complementary proton therapy irrespective of the quality of resection is now routinely proposed even if its efficacy is not clearly demonstrated in case of incomplete resection. The future of CH treatment is certainly related to a better understanding of the molecular biology and oncogenesis of CHs and consequently to the development of efficient targeted chemotherapies. PMID- 26141363 TI - The Endoscopic Endonasal Approach for Removal of Petroclival Chondrosarcomas. AB - Chondrosarcomas of the skull base are rare, locally invasive tumors that typically arise in the petroclival region, from degenerated chondroid cells located within the synchondrosis. Given their usually slow growth rate, they are capable of reaching sizable dimensions, promoting bone erosion and significant displacement of neurovascular structures before causing symptomatology that will eventually lead to diagnosis; cranial neuropathies and headaches are common complaints. This article discusses the pertinent surgical anatomy, patient selection criteria, technical nuances and complication management of the endonasal resection of skull base chondrosarcomas. PMID- 26141364 TI - Endoscopic Endonasal Management of Orbital Pathologies. AB - Based on the anatomic relationship between sinonasal complex and orbit, endoscopic transnasal procedures could be a smart solution for approaching the medial orbital region. These techniques should be considered a valid option for optic nerve or orbital wall decompression in cases of Graves ophthalmopathy and post-traumatic optic neuropathy as well as for addressing extraconal or intraconal lesions placed medially to the optic nerve course. This article describes the anatomic principles, indications, technical nuances, and limitations of the endoscopic endonasal approaches for the management of selected orbital pathologic abnormalities. PMID- 26141365 TI - Endoscopic Endonasal Resection of Trigeminal Schwannomas. AB - The surgical management of trigeminal schwannomas (TNs) entails the use of a variety of cranial base approaches for their effective surgical management. Although an extended middle fossa or posterior petrosal approach may be more appropriate for disease with primarily posterior fossa involvement, the expanded endoscopic approaches are suited for tumors with predominately middle fossa and/or extracranial involvement along the V2 and V3 divisions and limited posterior fossa extension. The endoscopic endonasal resection of TNs within the middle fossa, pterygopalatine fossa, and infratemporal fossa is reviewed in this article with a brief discussion of reported outcomes. PMID- 26141366 TI - Neurosurgery Clinics of North America. Endoscopic Endonasal Skull Base Surgery. Preface. PMID- 26141367 TI - Deficiency of sorting nexin 10 prevents bone erosion in collagen-induced mouse arthritis through promoting NFATc1 degradation. AB - OBJECTIVE: Periarticular and subchondral bone erosion in rheumatoid arthritis caused by osteoclast differentiation and activation is a critical index for diagnosis, therapy and monitoring of the disease. Sorting nexin (SNX) 10, a member of the SNX family which functions in regulation of endosomal sorting, has been implicated to play an important clinical role in malignant osteopetrosis. Here we studied the roles and precise mechanisms of SNX10 in the bone destruction of collagen-induced arthritis (CIA) mice. METHODS: The role of SNX10 in bone destruction was evaluated by a CIA mice model which was induced in male SNX10(-/ ) mice and wild type littermates. The mechanism was explored in osteoclasts induced by receptor activator of nuclear factor kappaB ligand from bone marrow mononuclear cells of wild type and SNX10(-/-) mice. RESULTS: SNX10 knockout prevented bone loss and joint destruction in CIA mice with reduced serum levels of TNF-alpha, interleukin 1beta and anticollagen IgG 2alpha antibody. SNX10 deficiency did not block osteoclastogenesis, but significantly impaired osteoclast maturation and bone-resorption function by disturbing the formation of actin belt. The production of TRAP, CtsK and MMP9 in SNX10(-/-) osteoclasts was significantly inhibited, and partially restored by SNX10 overexpression. We further demonstrated that the degradation of NFATc1 was accelerated in SNX10(-/-) osteoclasts causing an inhibition of integrin beta3-Src-PYK2 signalling. CONCLUSIONS: Our study discloses a crucial role and novel mechanism for SNX10 in osteoclast function, and provides evidence for SNX10 as a promising novel therapeutic target for suppression of immune inflammation and bone erosion in rheumatoid arthritis. PMID- 26141368 TI - Recruitment of CD8(+) T cells into bone marrow might explain the suppression of megakaryocyte apoptosis through high expression of CX3CR1(+) in prolonged isolated thrombocytopenia after allogeneic hematopoietic stem cell transplantation. AB - Prolonged isolated thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is associated with a poor prognosis. This study aimed to investigate the pathogenesis of prolonged isolated thrombocytopenia (PT). We analysed the expression of CX3CR1 on CD4 and CD8 T cells in bone marrow (BM) and peripheral blood (PB) at +90 days from allo HSCT recipients with or without PT by flow cytometry analyses. We then determined the megakaryocytes ploidy distributions, apoptosis rate and Fas expression of recipients with or without PT in vitro directly or after depleting CD8(+) T cells or adding purified autologous CD8(+) T cells to CD8(+) T-dep MNCs. We found that the percentage of CD8(+) T cells in BM was higher in the patients with PT than in the controls. The elevated expression of the CX3CR1 was associated with PT. There was a marked increase in the percentage of low ploidy megakaryocytes in the recipients with PT. The depletion of CD8(+) T cells increased the apoptosis of megakaryocytes and decreased the expression of Fas, which could be corrected by re-adding purified autologous CD8(+) T cells. The increase of CD8(+) T cells and CD8(+)/CX3CR1(+) T cells in BM at +90 days were independent risk factors for PT according to multivariate analysis. Our data implied that the recruitment of CD8(+) T cells into BM might explain the suppression of megakaryocyte apoptosis through the elevated expression of CX3CR1(+) in PT after allo-HSCT. CX3CR1 might be a novel treatment target in recipients with PT. PMID- 26141369 TI - A prospective study of incidence, clinical and quality of life consequences of oral mucositis post palifermin prophylaxis in patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation. AB - Autologous hematopoietic cell transplantation (AHCT) has presented a revolutionary advance in the management of hematologic malignancies with low toxicity. However, oral mucositis (OM) remains a distressing toxic effect of AHCT and one of the major side effects of the conditioning. This prospective, observational study aimed to evaluate the severity of oral cavity pain and quality of life (QOL) and explore incidence, duration, and potential risk factors of moderate/severe OM. Thirty-nine patients receiving prophylactic palifermin post-AHCT were enrolled. QOL and severity of pain were assessed using validated questionnaires (Functional Assessment of Cancer Therapy-General (FACT-G) and mouth and throat soreness (MTS), respectively). The incidence of moderate/severe OM was 28.2 % with a median duration of 5 days and was associated with younger age and female gender. Severity of pain related to OM was generally low or moderate with only 25 % of patients reporting a score >6 on the MTS scale of 0-10 on day +7. Health-related QOL was worse on day +7 in the transplant unit compared to day 1, while on discharge day, all scores recovered and the total FACT-G score was not different from that on day 1. In our population, the incidence and duration of OM and the severity of pain related to OM appeared to be lower compared to that reported in previous studies. The impact of OM on QOL assessments seemed to be reversible with optimal supportive care despite the major transient disabilities mainly attributable to OM. PMID- 26141371 TI - Muscular strength after total hip arthroplasty. A prospective comparison of 3 surgical approaches. AB - BACKGROUND AND PURPOSE: Minimizing the decrease in muscular strength after total hip arthroplasty (THA) might allow patients to recover faster. We evaluated muscular strength in patients who were operated on using 3 surgical approaches. PATIENTS AND METHODs: In a prospective cohort study, 60 patients scheduled for primary THA were allocated to the direct lateral, posterior, or anterior approach. Leg press and abduction strength were evaluated 2 weeks or less preoperatively, 2 and 8 days postoperatively, and at 6-week and 3-month follow up. RESULTS: Differences in maximal strength change were greatest after 2 and 8 days. The posterior and anterior approaches produced less decrease in muscular strength than the direct lateral approach. 6 weeks postoperatively, the posterior approach produced greater increase in muscular strength than the direct lateral approach, and resulted in a greater increase in abduction strength than the anterior approach. At 3-month follow-up, no statistically significant differences between the groups were found. The operated legs were 18% weaker in leg press and 15% weaker in abduction than the unoperated legs, and the results were similar between groups. INTERPRETATION: The posterior and anterior approaches appeared to have the least negative effect on abduction and leg press muscular strength in the first postoperative week; the posterior approach had the least negative effect, even up to 6 weeks postoperatively. THA patients have reduced muscle strength in the operated leg (compared to the unoperated leg) 3 months after surgery. PMID- 26141372 TI - Comparative Thermal Degradation Patterns of Natural Yellow Colorants Used in Foods. AB - There is a great interest in natural yellow colorants due to warnings issued about certain yellow food colorings of synthetic origin. However, no comparative studies have been reported of their thermal stability. For this reason, the thermal stabilities of six natural yellow colorants used in foods--lutein, riboflavin, curcumin, beta-carotene, gardenia yellow and Opuntia betaxanthins- were studied in simple solutions over a temperature range 30-90 degrees C. Spectral properties and visual color were investigated during 6 h of heat treatment. Visual color was monitored from the CIEL*a*b* parameters. The remaining absorbance at maximum wavelength and the total color difference were used to quantify color degradation. The rate of color degradation increased as the temperature rose. The results showed that the thermal degradation of the colorants followed a first-order reaction kinetics. The reaction rate constants and half-life periods were determined as being central to understanding the color degradation kinetics. The temperature-dependent degradation was adequately modeled on the Arrhenius equation. Activation energies ranged from 3.2 kJmol(-1) (lutein) to 43.7 kJmol(-1) (Opuntia betaxanthins). beta-carotene and lutein exhibited high thermal stability, while betaxanthins and riboflavin degraded rapidly as temperature increased. Gardenia yellow and curcumin were in an intermediate position. PMID- 26141370 TI - Generation of low-flux X-ray micro-planar beams and their biological effect on a murine subcutaneous tumor model. AB - We generated low-flux X-ray micro-planar beams (MPBs) using a laboratory-scale industrial X-ray generator (60 kV/20 mA) with custom-made collimators with three different peak/pitch widths (50/200 MUm, 100/400 MUm, 50/400 MUm). To evaluate normal skin reactions, the thighs of C3H/HeN mice were exposed to 100 and 200 Gy MPBs in comparison with broad beams (20, 30, 40, 50, 60 Gy). Antitumor effects of MPBs were evaluated in C3H/HeN mice with subcutaneous tumors (SCCVII). After the tumors were irradiated with 100 and 200 Gy MPBs and 20 and 30 Gy broad beams, the tumor sizes were measured and survival analyses were performed. In addition, the tumors were excised and immunohistochemically examined to detect gamma-H2AX, ki67 and CD34. It was shown that antitumor effects of 200 Gy MPBs at 50/200 MUm and 100/400 MUm were significantly greater than those of 20 Gy broad beams, and were comparable with 30 Gy broad beams. gamma-H2AX-positive cells demonstrated clear stripe-patterns after MPB irradiation; the pattern gradually faded and intermixed over 24 h. The chronological changes in ki67 positivity did not differ between MPBs and broad beams, whereas the CD34-positive area decreased significantly more in MPBs than in broad beams. In addition, it was shown that skin injury after MPB irradiation was significantly milder when compared with broad-beam irradiation at equivalent doses for achieving the same tumor control effect. Bystander effect and tumor vessel injury may be the mechanism contributing to the efficacy of MPBs. PMID- 26141373 TI - Safety and feasibility of the new 5 Fr Glidesheath Slender. AB - The aim of this study was to evaluate the safety and feasibility of the new 5 Fr Glidesheath Slender (GSS). The transradial (TR) approach has become popular because of several advantages, such as a reduced rate of vascular access site complications. However, because the radial artery is narrow, a limitation of TR access is the potential for artery spasm or occlusion. Studies of radial artery size demonstrate that 5 Fr sheaths are too wide for more than 10 % of patients. The GSS (Terumo, Tokyo, Japan) is a new radial sheath with a thinner wall and a hydrophilic coating. It has an inner diameter that is compatible with a 5 Fr guiding catheter, while the outer diameter is similar to that of a 4 Fr sheath. A total of 21 consecutive patients undergoing transradial angiography and/or transradial percutaneous coronary intervention with the 5 Fr GSS were included, and safety and feasibility of the device were assessed. Transradial angiography was performed in 10 patients, and transradial intervention in 11 patients. All procedures were successful, without the need for conversion to the transfemoral approach. The radial artery occlusion rate was 0 %, including a patient who had experienced six previous radial artery punctures. There were no cases of artery spasm, hematoma, major bleeding or functional disorders. One coronary artery perforation caused by a guidewire was reported, but it was unrelated to the sheath introducer. The new 5 Fr GSS was safe and feasible for transradial angiography and transradial intervention. PMID- 26141376 TI - Improvement of the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production by dual feeding with levulinic acid and sodium propionate in Cupriavidus necator. AB - In the context of increasing volatility of oil prices, replacement of petroleum based plastics by bioplastics is a topic of increasing interest. Poly(hydroxyalkanoate)s (PHAs) are among the most promising families in this field. Controlling composition of the polymer on the monomeric level remains a pivotal issue. This control is even more difficult to achieve when the polymer is not synthesized by chemists, but produced by nature, in this case, bacteria. In this study mechanism and role of two 3-hydroxyvalerate (3-HV) inducing substrates on the production of PHBV with high, 80%, 3-HV content were evaluated. It was found that levulinic acid contributes to biomass and bio-polymer content enhancement, whereas sodium propionate mainly contributes to 3-HV enhancement. Optimized proportions of feeding substrates at 1 g/L and 2.5 g/L, respectively for levulinic acid and sodium propionate allowed a 100% productivity enhancement, at 3.9 mg/L/hour, for the production of PHBV with 80% 3-HV. PMID- 26141375 TI - Coping strategies and postpartum depressive symptoms: A structural equation modelling approach. AB - BACKGROUND: Variables such as the mother's personality, social support, coping strategies and stressful events have been described as risk factors for postpartum depression. Structural Equation Modelling (SEM) analysis was used to examine whether neuroticism, perceived social support, perceived life events, and coping strategies are associated with postpartum depressive symptoms at the 8th and 32nd weeks. METHODS: A total of 1626 pregnant women participated in a longitudinal study. Different evaluations were performed 8 and 32weeks after delivery. Several measures were used: the Edinburgh Postnatal Depression Scale (EPDS), the Diagnostic Interview for Genetic Studies (DIGS), the Eysenck Personality Questionnaire (EPQ-RS), the St. Paul Ramsey life events scale and the Duke-UNC Functional Social Support Questionnaire. The brief COPE scale was used to measure coping strategies. SEM analysis was conducted for all women and in those women with a clinical diagnosis of postpartum depression. RESULTS: Passive coping strategies were associated with postpartum depressive symptoms at both visits (8th and 32nd weeks). Neuroticism was associated with more passive coping strategies and less active coping strategies. Neuroticism and life stress were positively correlated, and social support was negatively correlated with life stress and neuroticism. CONCLUSIONS: Early identification of potential risk for symptomatology of depression postpartum should include assessment of neuroticism, life events, social support and coping strategies. PMID- 26141374 TI - Comparison of the structure, function and autophagic maintenance of mitochondria in nigrostriatal and tuberoinfundibular dopamine neurons. AB - A pathological hallmark of Parkinson's disease (PD) is progressive degeneration of nigrostriatal dopamine (NSDA) neurons, which underlies the motor symptoms of PD. While there is severe loss of midbrain NSDA neurons, tuberoinfundibular (TI) DA neurons in the mediobasal hypothalamus (MBH) remain intact. In the present study, confocal microscopic analysis revealed that mitochondrial content and numbers of mitophagosomes were lower in NSDA neuronal cell bodies in the substantia nigra pars compacta (SNpc) compared to TIDA neuronal cell bodies in the arcuate nucleus (ARC) of C57BL/6J male mice. Mitochondrial respiration, mass, membrane potential and morphology were determined using bioenergetic, flow cytometric and transmission electron microscopic analyses of synaptosomes isolated from discrete brain regions containing axon terminals of NSDA and TIDA neurons. Maximum and spare respiratory capacities, and mitochondrial mass were lower in synaptosomal mitochondria derived from the striatum (ST) as compared with the MBH, which correlated with lower numbers of mitochondria per synaptosome in these brain regions. In contrast, there was no regional difference in mitochondrial basal, maximum or spare respirations following inhibition of Complex I activity with rotenone. These results reveal that higher numbers of viable mitochondria are correlated with more extensive autophagic mitochondrial quality maintenance in TIDA neurons as compared with NSDA neurons. PMID- 26141377 TI - Electron self-exchange in hemoglobins revealed by deutero-hemin substitution. AB - Hemoglobins (phytoglobins) from rice plants (nsHb1) and from the cyanobacterium Synechocystis (PCC 6803) (SynHb) can reduce hydroxylamine with two electrons to form ammonium. The reaction requires intermolecular electron transfer between protein molecules, and rapid electron self-exchange might play a role in distinguishing these hemoglobins from others with slower reaction rates, such as myoglobin. A relatively rapid electron self-exchange rate constant has been measured for SynHb by NMR, but the rate constant for myoglobin is equivocal and a value for nsHb1 has not yet been measured. Here we report electron self-exchange rate constants for nsHb1 and Mb as a test of their role in hydroxylamine reduction. These proteins are not suitable for analysis by NMR ZZ exchange, so a method was developed that uses cross-reactions between each hemoglobin and its deutero-hemin substituted counterpart. The resulting electron transfer is between identical proteins with low driving forces and thus closely approximates true electron self-exchange. The reactions can be monitored spectrally due to the distinct spectra of the prosthetic groups, and from this electron self-exchange rate constants of 880 (SynHb), 2900 (nsHb1), and 0.05M(-1) s(-1) (Mb) have been measured for each hemoglobin. Calculations of cross-reactions using these values accurately predict hydroxylamine reduction rates for each protein, suggesting that electron self-exchange plays an important role in the reaction. PMID- 26141378 TI - Optimal decoding and information transmission in Hodgkin-Huxley neurons under metabolic cost constraints. AB - Information theory quantifies the ultimate limits on reliable information transfer by means of the channel capacity. However, the channel capacity is known to be an asymptotic quantity, assuming unlimited metabolic cost and computational power. We investigate a single-compartment Hodgkin-Huxley type neuronal model under the spike-rate coding scheme and address how the metabolic cost and the decoding complexity affects the optimal information transmission. We find that the sub-threshold stimulation regime, although attaining the smallest capacity, allows for the most efficient balance between the information transmission and the metabolic cost. Furthermore, we determine post-synaptic firing rate histograms that are optimal from the information-theoretic point of view, which enables the comparison of our results with experimental data. PMID- 26141379 TI - Intrauterine administration of human chorionic gonadotropin does not improve pregnancy and life birth rates independently of blastocyst quality: a randomised prospective study. AB - BACKGROUND: Successful embryo implantation depends on a well-timed maternal embryonic crosstalk. Human chorionic gonadotropin (hCG) secreted by the embryo is known to play a key role in this process and to trigger a complex signal transduction cascade allowing the apposition, attachment, and invasion of the embryo into the decidualized uterus. Production of hCG was reported to be dependent on blastocyst quality and several articles suggested that intrauterine hCG injection increases pregnancy and implantation rates in IVF patients. However, no study has as yet analysed birth rates as final outcome. Our objective was to determine whether clinical outcome after blastocyst transfer can be improved by intrauterine injection of hCG and whether this is dependent on blastocyst quality. METHODS: A prospective randomised study was conducted in two settings. In cohort A, hCG application was performed two days before blastocyst transfer. In cohort B, the administration of hCG occurred just prior to embryo transfer on day 5. For both cohorts, patients were randomised to either intrauterine hCG application or to the control group that received culture medium. Clinical outcome was analysed according to blastocyst quality of transferred embryos. RESULTS: The outcome of 182 IVF-cycles (cohort A) and 1004 IVF-cycles (cohort B) was analysed. All patients received a fresh autologous blastocyst transfer on day five. Primary outcomes were pregnancy rates (PR), clinical pregnancy rates (cPR), miscarriage rates (MR), and live birth rates (LBR). No improvement of clinical outcome after intrauterine hCG administration on day 3 (cohort A) or day 5 (cohort B) was found, independently of blastocyst quality transferred. The final outcome in cohort A: LBR after transfer of top blastocysts was 50.0 % with hCG and 53.3 % in the control group. With non-top blastocysts, LBR of 17.1 % (hCG) and 18.2 % (control) were observed (n.s.). In cohort B, LBR with top blastocysts was 53.3 % (hCG) and 48.4 % (control), with non-top blastocysts it came to 28.7 % (hCG) and 35.0 % (control). The differences between the groups were statistically not significant. Furthermore, we investigated a possible benefit of hCG administration in correlation with female age. In both age groups (<38 years and >= 38 years) we found similar LBR after treatment with hCG vs. medium. A LBR of 47.1 % vs. 48.7 % was obtained in the younger group and 26.6 % vs. 30.8 % in the older group. CONCLUSIONS: In contrast to previous studies indicating a substantial benefit from intrauterine hCG application in cleavage stage embryo transfers, in our study we could not find any evidence for improvement of clinical outcome in blastocyst transfer cycles, neither with top nor with non-top quality morphology. PMID- 26141381 TI - Migraine is associated with an increased risk for benign paroxysmal positional vertigo: a nationwide population-based study. AB - BACKGROUND: There is evidence suggesting that migraine may be associated with vertigo. The aim of this study was to assess the risk of benign paroxysmal positional vertigo (BPPV), the most common form of vertigo, in patients with migraine using a population-based dataset. METHODS: The National Health Insurance Research Database in Taiwan was searched for migraine patients and was also used to select an age- and sex-matched cohort of subjects without migraine. The analyses included 8266 migraine patients and 8266 controls. The incidence rates of BPPV in the two cohorts were compared. Cox proportional hazard models were used to identify risk factors for BPPV in migraine patients. RESULTS: In the migraine cohort, 1.11% of the patients developed BPPV compared to 0.5% of the controls. The incidence rate ratio was 2.03 (95% CI 1.41-2.97; p <0.001). Cox proportional hazards analysis showed that age >=40 years (HR 2.20; 95% CI 1.40 3.45; p = 0.001), coronary artery disease (HR 4.62; 95% CI 1.12-19.01; p = 0.034), and the number of outpatient department visits to neurologists because of migraine (HR 2.93; 95% CI 2.50-3.44; p >0.001) were associated with an increased risk for BPPV. CONCLUSION: The results showed that patients with migraine had a 2.03-fold increased risk of developing BPPV compared with age- and sex-matched controls. Although BPPV may not be a common condition in migraine patients, migraine sufferers with vestibular symptoms should alert physicians to the possibility of BPPV, particularly if patients are aged >=40 years, have a history of coronary artery disease, or have frequent visits to neurologists clinics because of migraine. PMID- 26141382 TI - Transplantation of a Donor Heart Following a Lightning Strike: MRI Identification of Myocardial Injury. PMID- 26141380 TI - Helicobacter pylori HP0377, a member of the Dsb family, is an untypical multifunctional CcmG that cooperates with dimeric thioldisulfide oxidase HP0231. AB - BACKGROUND: In the genome of H. pylori 26695, 149 proteins containing the CXXC motif characteristic of thioldisulfide oxidoreductases have been identified to date. However, only two of these proteins have a thioredoxin-like fold (i.e., HP0377 and HP0231) and are periplasm-located. We have previously shown that HP0231 is a dimeric oxidoreductase that catalyzes disulfide bond formation in the periplasm. Although HP0377 was originally described as DsbC homologue, its resolved structure and location of the hp0377 gene in the genome indicate that it is a counterpart of CcmG/DsbE. RESULTS: The present work shows that HP0377 is present in H. pylori cells only in a reduced form and that absence of the main periplasmic oxidase HP0231 influences its redox state. Our biochemical analysis indicates that HP0377 is a specific reductase, as it does not reduce insulin. However, it possesses disulfide isomerase activity, as it catalyzes the refolding of scrambled RNase. Additionally, although its standard redox potential is -176 mV, it is the first described CcmG protein having an acidic pKa of the N-terminal cysteine of the CXXC motif, similar to E. coli DsbA or E. coli DsbC. The CcmG proteins that play a role in a cytochrome c-maturation, both in system I and system II, are kept in the reduced form by an integral membrane protein DsbD or its analogue, CcdA. In H. pylori HP0377 is re-reduced by CcdA (HP0265); however in E. coli it remains in the oxidized state as it does not interact with E. coli DsbD. Our in vivo work also suggests that both HP0377, which plays a role in apocytochrome reduction, and HP0378, which is involved in heme transport and its ligation into apocytochrome, provide essential functions in H. pylori. CONCLUSIONS: The present data, in combination with the resolved three-dimensional structure of the HP0377, suggest that HP0377 is an unusual, multifunctional CcmG protein. PMID- 26141384 TI - Policy implications of medical tourism development in destination countries: revisiting and revising an existing framework by examining the case of Jamaica. AB - BACKGROUND: Medical tourism is now targeted by many hospitals and governments worldwide for further growth and investment. Southeast Asia provides what is perhaps the best documented example of medical tourism development and promotion on a regional scale, but interest in the practice is growing in locations where it is not yet established. Numerous governments and private hospitals in the Caribbean have recently identified medical tourism as a priority for economic development. We explore here the projects, activities, and outlooks surrounding medical tourism and their anticipated economic and health sector policy implications in the Caribbean country of Jamaica. Specifically, we apply Pocock and Phua's previously-published conceptual framework of policy implications raised by medical tourism to explore its relevance in this new context and to identify additional considerations raised by the Jamaican context. METHODS: Employing case study methodology, we conducted six weeks of qualitative fieldwork in Jamaica between October 2012 and July 2013. Semi-structured interviews with health, tourism, and trade sector stakeholders, on-site visits to health and tourism infrastructure, and reflexive journaling were all used to collect a comprehensive dataset of how medical tourism in Jamaica is being developed. Our analytic strategy involved organizing our data within Pocock and Phua's framework to identify overlapping and divergent issues. RESULTS: Many of the issues identified in Pocock and Phua's policy implications framework are echoed in the planning and development of medical tourism in Jamaica. However, a number of additional implications, such as the involvement of international development agencies in facilitating interest in the sector, cyclical mobility of international health human resources, and the significance of health insurance portability in driving the growth of international hospital accreditation, arise from this new context and further enrich the original framework. CONCLUSIONS: The framework developed by Pocock and Phua is a flexible common reference point with which to document issues raised by medical tourism in established and emerging destinations. However, the framework's design does not lend itself to explaining how the underlying health system factors it identifies work to facilitate medical tourism's development or how the specific impacts of the practice are likely to unfold. PMID- 26141385 TI - The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas. AB - Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear. We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 and at Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus on chromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss was a common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, which lacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after early irradiation (60%) than after young adult irradiation (30%). Homozygous Pten mutations occurred without DNA copy number change after irradiation starting in infancy, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that while deletions on chromosomes 4 and 11 affecting Cdkn2a and Ikaros are a prominent feature of young adult irradiation-induced T cell lymphoma, tumors arising after irradiation from infancy suffer a second hit in Pten by mis-segregation or recombination. This is the first report showing an influence of age-at-exposure on genomic alterations of tumor suppressor genes and their relative involvement in radiation-induced T-cell lymphoma. These data are important for considering the risks associated with childhood exposure to radiation. PMID- 26141386 TI - Optimization of ultrasonic extraction of polysaccharides from Hovenia dulcis peduncles and their antioxidant potential. AB - An ultrasonic-assisted extraction of polysaccharides from the ripe peduncles of Hovenia dulcis (HDPs) was investigated. Response surface methodology along with a Box-Behnken design based on single-factor experiments was employed to optimize and model the extraction conditions of HDPs, namely extraction temperature (40-60 degrees C), ultrasonic power (320-480 W) and extraction time (35-65 min). The optimized conditions were extraction temperature 60 degrees C, ultrasonic power 362 W and extraction time 65 min. Under these conditions, the maximal yield of crude HDPs was 25.12+/-0.145 mg/g DW, which is consistent with the predictive yield of 25.33 mg/g DW. The polysaccharides were graded by an ethanol precipitation method and three fractions (HDPs1, HDPs2 and HDPs3) were harvested. These had final ethanol concentrations of 40%, 60% and 80%, respectively and were acidic polysaccharides. The preliminary characterization was mainly composed of Ara, Rha, Glu and Gal, and exhibited an almost similar characteristic absorption peak by gas chromatograph and infrared spectra analysis. The antioxidant activity assays in vitro revealed that HDPs can be used as natural antioxidants in functional foods and pharmaceutical industries. PMID- 26141387 TI - Anti-fatigue activity of a novel polysaccharide conjugates from Ziyang green tea. AB - The aim of this study was to investigate the anti-fatigue activity of polysaccharides from Ziyang green tea. Polysaccharides were isolated from Ziyang green tea and its physicochemical properties were analyzed. Meanwhile, a 4-week weight-loaded swimming test of mice was established and polysaccharides were orally administrated during exercise. The biochemical parameters related to fatigue were determined, such as exhaustive time, blood urea nitrogen (BUN), blood lactate acid (Bla) levels and lactic dehydrogenase (LDH) activity in serum, Superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px) activities, Malondialdehyde (MDA) and glycogen levels in skeletal muscle. The results demonstrated that polysaccharide from Ziyang green tea was a selenium polysaccharide-protein conjugate (Se-TP), and Se-TP administration significantly prolonged exhaustive time and increased glycogen level and GSH-Px activity in muscle, in addition, markedly decreased BUN, Bla levels and LDH activity in serum and MDA level in muscle. In conclusion, Se-TP treatment can significantly improve exercise-induced fatigue and decrease the oxidative stress induced by the exhaustive exercise. PMID- 26141388 TI - Polychlorinated Biphenyls (PCB 101, 153, and 180) Impair Murine Macrophage Responsiveness to Lipopolysaccharide: Involvement of NF-kappaB Pathway. AB - Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) are persistent organic pollutants, associated with a range of adverse health effects, including interference with the immune system. In this study, we investigate the capability of NDL-PCBs 101, 153, and 180, 3 of the 6 NDL-PCBs defined as indicators, to impair the immune response in lipopolysaccharide (LPS)-activated J774A.1 and primary murine macrophages. Our results clearly demonstrate that the exposure of J774A.1 and primary macrophages to NDL-PCB 153 or 180 or all NDL-PCBs mixtures causes a significant reduction in LPS-induced cytokine/chemokine synthesis, such as tumor necrosis factor-alpha and interleukin-6, together with monocyte chemoattractant protein-1, involved in cell recruitment. Moreover, PCBs were found to suppress LPS-stimulated NO production, and to reduce cyclooxygenase-2 and inducible nitric oxide synthase expression in J774A.1 and primary macrophages. At mechanistic level, PCBs significantly counteract the LPS-driven toll-like receptor (TLR) 4 and CD14 upregulation, therefore inhibiting downstream nuclear factor-kappaB (NF-kappaB) activation in J774A.1. Furthermore, PCBs determine a significant loss of macrophage endocytic capacity, a prerequisite for efficient antigen presentation. Taken together, these data indicate that NDL-PCBs reduce macrophage responsiveness, particularly when they are combined at concentrations per se inactive, impairing the capability to orchestrate a proper immune response to an infectious stimulus, disrupting TLR4/NF-kappaB pathway. PMID- 26141389 TI - Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library. AB - Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ERalpha) agonists, screening in the presence of testosterone (T) identifies AIs and/or ERalpha antagonists, and screening in the presence of 17beta-estradiol (E2) identifies ERalpha antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase. PMID- 26141392 TI - Systems Biology Reveals Cigarette Smoke-Induced Concentration-Dependent Direct and Indirect Mechanisms That Promote Monocyte-Endothelial Cell Adhesion. AB - Cigarette smoke (CS) affects the adhesion of monocytes to endothelial cells, a critical step in atherogenesis. Using an in vitro adhesion assay together with innovative computational systems biology approaches to analyze omics data, our study aimed at investigating CS-induced mechanisms by which monocyte-endothelial cell adhesion is promoted. Primary human coronary artery endothelial cells (HCAECs) were treated for 4 h with (1) conditioned media of human monocytic Mono Mac-6 (MM6) cells preincubated with low or high concentrations of aqueous CS extract (sbPBS) from reference cigarette 3R4F for 2 h (indirect treatment, I), (2) unconditioned media similarly prepared without MM6 cells (direct treatment, D), or (3) freshly generated sbPBS (fresh direct treatment, FD). sbPBS promoted MM6 cells-HCAECs adhesion following I and FD, but not D. In I, the effect was mediated at a low concentration through activation of vascular inflammation processes promoted in HCAECs by a paracrine effect of the soluble mediators secreted by sbPBS-treated MM6 cells. Tumor necrosis factor alpha (TNFalpha), a major inducer, was actually shed by unstable CS compound-activated TNFalpha converting enzyme. In FD, the effect was triggered at a high concentration that also induced some toxicity. This effect was mediated through an yet unknown mechanism associated with a stress damage response promoted in HCAECs by unstable CS compounds present in freshly generated sbPBS, which had decayed in D unconditioned media. Aqueous CS extract directly and indirectly promotes monocytic cell-endothelial cell adhesion in vitro via distinct concentration dependent mechanisms. PMID- 26141390 TI - Ligand-Specific Transcriptional Mechanisms Underlie Aryl Hydrocarbon Receptor Mediated Developmental Toxicity of Oxygenated PAHs. AB - Polycyclic aromatic hydrocarbons (PAHs) are priority environmental contaminants that exhibit mutagenic, carcinogenic, proinflammatory, and teratogenic properties. Oxygen-substituted PAHs (OPAHs) are formed during combustion processes and via phototoxidation and biological degradation of parent (unsubstituted) PAHs. Despite their prevalence both in contaminated industrial sites and in urban air, OPAH mechanisms of action in biological systems are relatively understudied. Like parent PAHs, OPAHs exert structure-dependent mutagenic activities and activation of the aryl hydrocarbon receptor (AHR) and cytochrome p450 metabolic pathway. Four-ring OPAHs 1,9-benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) cause morphological aberrations and induce markers of oxidative stress in developing zebrafish with similar potency, but only 7,12-B[a]AQ induces robust Cyp1a protein expression. We investigated the role of the AHR in mediating the toxicity of BEZO and 7,12 B[a]AQ, and found that knockdown of AHR2 rescued developmental effects caused by both compounds. Using RNA-seq and molecular docking, we identified transcriptional responses that precede developmental toxicity induced via differential interaction with AHR2. Redox-homeostasis genes were affected similarly by these OPAHs, while 7,12-B[a]AQ preferentially activated phase 1 metabolism and BEZO uniquely decreased visual system genes. Analysis of biological functions and upstream regulators suggests that BEZO is a weak AHR agonist, but interacts with other transcriptional regulators to cause developmental toxicity in an AHR-dependent manner. Identifying ligand-dependent AHR interactions and signaling pathways is essential for understanding toxicity of this class of environmentally relevant compounds. PMID- 26141391 TI - Dosimetry of Acrylamide and Glycidamide Over the Lifespan in a 2-Year Bioassay of Acrylamide in Wistar Han Rats. AB - Acrylamide is an industrial chemical used to manufacture polymers, and is produced in foods during cooking at high heat. Hemoglobin adducts provide a long lived dosimeter for acrylamide and glycidamide. This study determined acrylamide and glycidamide hemoglobin adducts (AAVal and GAVal) during a lifetime carcinogenesis bioassay. Exposure to acrylamide in drinking water began in utero in pregnant rats on gestation day 6. Dams were administered acrylamide until weaning, and male and female F1 rats were exposed for a further 104 weeks. Acrylamide concentration in drinking water was adjusted to provide a constant dose of 0.5, 1.5, and 3 mg/kg/day. Blood was collected from animals euthanized at 2, 60, 90, and 120 days and 53, 79, and 104 weeks after weaning. Low levels of AAVal and GAVal at postnatal day 24 suggested that little exposure to acrylamide occurred by placental or lactational transfer, and extensive metabolism to glycidamide occurred with a GAVal:AAVal ratio of 4. Adduct levels varied somewhat from 60 days to 2 years, with a GAVal:AAVal ratio of approximately 1. Adduct formation/day estimated at each timepoint at 3 mg/kg/day for AAVal was 1293 +/- 220 and 1096 +/- 338 fmol/mg/day for male and female rats, respectively. Adduct formation per day estimated at each timepoint at 3 mg/kg/day for GAVal was 827 +/ 78 fmol/mg/day for male rats, and 982 +/- 222 fmol/mg/day for female rats. The study has provided estimates of linearity for dose response, and variability in internal dose throughout an entire 2-year bioassay, including the early phases of pregnancy and lactation. PMID- 26141393 TI - Long-term Fluorometholone Topical Use Induces Ganglion Cell Damage in Rats Analyzed With Optical Coherence Tomography. AB - To determine the toxic effects of long-term topical usage of fluorometholone (FLM) on ganglion cells using a direct in vivo retinopathological Brown Norway (BN) rat model. The BN rat retinal model was investigated with a minimum of 3 rats and a maximum of 4 rats per group. Rats received vehicle and 0.02% FLM suspension via topical administration 3 times a day for 28 days. The fundus images and retinal vessels were detected on days 1, 14, and 28 using Micron III retinal imaging microscope and fundus fluorescein angiography (FFA). For retinal structures, spectral-domain optical coherence tomography (SD-OCT) images were taken after FFA on days 1, 14, and 28 using an SD-OCT Imaging System. For retinal function, electrical signal transduction of photoreceptors and bipolar cells was determined by electroretinographic (ERG) recording on days 1 and 28 and IOP detection. At the end of the experiment on day 28, immunohistochemistry and TUNEL assay were performed to investigate apoptosis in ganglion cells. Total retina and nerve fiber layer (NFL) to the inner plexiform layer (IPL) were significantly thinner following 28 days of FLM treatment. Hematoxylin and eosin stain showed that there were NFL and ganglion cell layer deformations in the FLM group. With FLM treatment, TUNEL assay showed approximately a 4.68-fold increase in apoptotic cells. Moreover, FLM decreased ERG b-wave amplitude by about 56%. Using ophthalmofundoscopy devices, after 28 days of topical administration, FLM decreased NFL-IPL and total retina thickness. This suggests that long-term FLM induces adverse effects with respect to ganglion cell apoptosis. PMID- 26141395 TI - An inoperable aortic arch interruption in a patient with differential cyanosis. PMID- 26141394 TI - Integrated Transcriptional and Proteomic Analysis of Growth Hormone Suppression Mediated by Trichothecene T-2 Toxin in Rat GH3 Cells. AB - Chronic exposure to trichothecenes is known to disturb insulin-like growth factor 1 and signaling of insulin and leptin hormones and causes considerable growth retardation in animals. However, limited information was available on mechanisms underlying trichothecene-induced growth retardation. In this study, we employed an integrated transcriptomics, proteomics, and RNA interference (RNAi) approach to study the molecular mechanisms underlying trichothecene cytotoxicity in rat pituitary adenoma GH3 cells. Our results showed that trichothecenes suppressed the synthesis of growth hormone 1 (Gh1) and inhibited the eukaryotic transcription and translation initiation by suppressing aminoacyl-tRNA synthetases transcription, inducing eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) and reducing eukaryotic translation initiation factor 5 a. The sulfhydryl oxidases , protein disulfide isomerase,and heat shock protein 90 (were greatly reduced, which resulted in adverse regulation of protein processing and folding. Differential genes and proteins associated with a decline in energy metabolism and cell cycle arrest were also found in our study. However, use of RNAi to interfere with hemopoietic cell kinase (Hck) and EIF2AK2 transcriptions or use of chemical inhibitors of MAPK, p38, Ras, and JNK partially reversed the reduction of Gh1 levels induced by trichothecenes. It indicated that the activation of MAPKs, Hck, and EIF2AK2 were important for trichothecene induced growth hormone suppression. Considering the potential hazards of exposure to trichothecenes, our findings could help to improve our understanding regarding human and animal health implications. PMID- 26141396 TI - A double barrelled myxoma. PMID- 26141398 TI - Radiotherapy-induced vascular damage in mammary arterial graft: correlations between optical coherence tomography and pathology. PMID- 26141399 TI - Massive bouncing right cardiac mass as a cause of persistent pulmonary embolism. PMID- 26141397 TI - Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data meta-analysis. AB - AIMS: The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT). METHODS AND RESULTS: Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta analysis models. This analysis included 2385 (OAC = 804 and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52-1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44-1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42-0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups. CONCLUSION: We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients. PMID- 26141400 TI - Genetic Counselors' Judgments of Patient Concerns: Concordance and Consequences. AB - The aims of this prospective study were to determine (a) the concordance between patient concerns and genetic counselors' judgments of these concerns, (b) the predictors of patient and counselor judgments, and (c) the relationship between concordance and patient outcomes. Patients' and counselors' views were sought before and after 131 routine genetic consultations. Before consultations, there was concordance about level of patient concern to within one point in 63% (82/131) of consultations and about type of patient concern in 60-84% of consultations. Lack of concordance in judging level and type of concern was associated with lower satisfaction with information and higher anxiety after the consultation. The biggest predictor of counselor judgment of concern was professional background: doctors judged patients to be more concerned than did nurses. Concordance of concern was predicted by counselors' experience in genetics: less experienced counselors overestimated patient concern. Future research needs to determine whether improving judgment of concern improves patient outcome. PMID- 26141401 TI - Editorial Introduction to "A Simple, Unified Approach to Bayesian Risk Calculations". PMID- 26141402 TI - A Simple, Unified Approach to Bayesian Risk Calculations. AB - A simple, unified approach for calculating Bayesian risks is presented and illustrated with examples. Although new genetic tools have reduced the need for these risk calculations, situations still exist in which consultands need to know these kinds of risks (for example, when no direct test is available for a particular deleterious mutation, or when a consultand wants to know his/her risk before deciding whether to undergo a direct test). The "Unified Approach" presented here is straightforward and ensures calculating the correct risks. It can be applied to a wide variety of genetic counseling situations, including but not limited to: calculating recurrence or carrier risks for dominant and recessive diseases; incorporating false-positive and false-negative rates on genetic tests into risk calculations; and determining the probability that an isolated case in a family represents a new mutation. The method is based on basic principles of probability and likelihood theory but can be used without sophisticated knowledge of this theory. The method relies on two rules, the "Rule of All Configurations" and the "Rule of Fundamental Probabilities," which are explained and illustrated. The Unified Approach does not represent new or original mathematics but should make it easier for users to calculate risks accurately. A warning is included that complex calculations should always be independently verified by another individual. PMID- 26141403 TI - Cancer Risk Assessment and Genetic Counseling in an Academic Medical Center: Consultands' Satisfaction, Knowledge, and Behavior in the First Year. AB - In 1995, we formally established a multifaceted cancer genetics program of clinical services, research, and education at a general academic medical center. In the first year, 58 families, mostly physician referred, received cancer risk assessment and genetic counseling for a family and/or medical history of cancer. The primary reasons for seeking consultation were to determine their risk or their offspring's risk for developing certain cancers and to inquire about the availability of DNA testing for predisposition to breast, ovarian, or colon cancers. To assess the level of satisfaction with program services, 51 consultands (22% with a personal history of cancer) were interviewed independently by telephone 3-12 months after the session. One goal of the survey was to improve program service. Ninety percent of respondents reported that the consultation was worth their time and money. Forty-two percent stated that their anxiety related to their cancer risk had decreased following counseling and 56% indicated no change. Recall of exact numerical risk was poor and one-third could not remember hearing any risk estimate. More respondents would recommend the service to friends (90%) than to family members (75%). Overall, the service was positively received by the majority of patients. PMID- 26141404 TI - Genetic Library. PMID- 26141405 TI - Errata. PMID- 26141406 TI - Impact of the Cytochrome P450 2B6 (CYP2B6) Gene Polymorphism c.516G>T (rs3745274) on Propofol Dose Variability. AB - BACKGROUND AND OBJECTIVES: Propofol is the most commonly used hypnotic worldwide, but its effective dose varies greatly between individuals. The present study sought to investigate the relationship between the c.516G>T polymorphism in the CYP2B6 (cytochrome P450 2B6) gene and the required propofol dose. METHODS: One hundred and eight patients treated with propofol were recruited, and environmental, clinical and surgical data were collected. Genotyping for the c.516G>T polymorphism was performed by real-time PCR. Multiple linear regression analysis was performed to estimate the predictive variables of the total propofol dose. RESULTS: For patients under general anaesthesia, the predictive variables of the total propofol dose were surgery duration (partial R (2) = 19.9 %), age (partial R (2) = 10.5 %), weight (partial R (2) = 10.1 %) and presence of the T allele (partial R (2) = 6.8 %). From the estimated coefficient of regression values, the surgery duration and weight were the factors that increased the propofol dose, while age and presence of the T allele decreased the total dose of the drug needed. The total propofol doses based on the GG or GT/TT genotypes were 151.5 +/- 64.2 mg and 129.3 +/- 44.6 mg, respectively (p = 0.043). CONCLUSIONS: Our results indicate that 34 % of the variance in the required propofol dose may be explained by these factors and that CYP2B6 c.516G>T polymorphism, which decreases the metabolism of the drug, accounts for approximately 7 % of the drug dosage. Our results show the possible influence of CYP2B6 c.516G>T genetic variant on propofol dose in patients under general anaesthesia. PMID- 26141407 TI - Fat/water ratios measured with diffuse reflectance spectroscopy to detect breast tumor boundaries. AB - Recognition of the tumor during breast-conserving surgery (BCS) can be very difficult and currently a robust method of margin assessment for the surgical setting is not available. As a result, tumor-positive margins, which require additional treatment, are not found until histopathologic evaluation. With diffuse reflectance spectroscopy (DRS), tissue can be characterized during surgery based on optical parameters that are related to the tissue morphology and composition. Here we investigate which optical parameters are able to detect tumor in an area with a mixture of benign and tumor tissue and hence which parameters are most suitable for intra-operative margin assessment. DRS spectra (400-1600 nm) were obtained from 16 ex vivo lumpectomy specimens from benign, tumor border, and tumor tissue. One mastectomy specimen was used with a custom made grid for validation purposes. The optical parameter related to the absorption of fat and water (F/W-ratio) in the extended near-infrared wavelength region (~1000-1600 nm) provided the best discrimination between benign and tumor sites resulting in a sensitivity and specificity of 100 % (excluding the border sites). Per patient, the scaled F/W-ratio gradually decreased from grossly benign tissue towards the tumor in 87.5 % of the specimens. In one test case, based on a predefined F/W-ratio for boundary tissue of 0.58, DRS produced a surgical resection plane that nearly overlapped with a 2-mm rim of benign tissue, 2 mm being the most widely accepted definition of a negative margin. The F/W-ratio provided excellent discrimination between sites clearly inside or outside the tumor and was able to detect the border of the tumor in one test case. This work shows the potential for DRS to guide the surgeon during BCS. PMID- 26141408 TI - BmVDAC upregulation in the midgut of Rhipicephalus microplus, during infection with Babesia bigemina. AB - The molecular mechanisms involved during the infection of Rhipicephalus microplus midgut cells by Babesia bigemina are of great relevance and currently unknown. In a previous study, we found a voltage-dependent anion channel (VDAC)-like protein (BmVDAC) that may participate during parasite invasion of midgut cells. In this work, we investigated BmVDAC expression at both mRNA and protein levels and examined BmVDAC localization in midgut cells of ticks infected with B. bigemina at different times post-repletion. Based on the RT-PCR results, Bmvdac expression levels were significantly higher in infected ticks compared to uninfected ones, reaching their highest values at 24h post-repletion (p<0.0001). Similar results were obtained at the protein level (p<0.0001). Interestingly, BmVDAC immunolocalization showed that there was an important differential expression and redistribution of BmVDAC protein between the midgut cells of infected and uninfected ticks, which was more evident 24h post-repletion of infected ticks. This is the first report of BmVDAC upregulation and immunolocalization in R. microplus midgut cells during B. bigemina infection. Further studies regarding the function of BmVDAC during the infection may provide new insights into the molecular mechanisms between B. bigemina and its tick vector and could result in its use as an anti-tick and transmission-blocking vaccine candidate. PMID- 26141409 TI - Revisiting macronutrient regulation in the polyphagous herbivore Helicoverpa zea (Lepidoptera: Noctuidae): New insights via nutritional geometry. AB - Insect herbivores that ingest protein and carbohydrates in physiologically optimal proportions and concentrations show superior performance and fitness. The first-ever study of protein-carbohydrate regulation in an insect herbivore was performed using the polyphagous agricultural pest Helicoverpa zea. In that study, experimental final instar caterpillars were presented two diets - one containing protein but no carbohydrates, the other containing carbohydrates but no protein - and allowed to self-select their protein-carbohydrate intake. The results showed that H. zea selected a diet with a protein-to-carbohydrate (p:c) ratio of 4:1. At about this same time, the geometric framework (GF) for the study of nutrition was introduced. The GF is now established as the most rigorous means to study nutrient regulation (in any animal). It has been used to study protein carbohydrate regulation in several lepidopteran species, which exhibit a range of self-selected p:c ratios between 0.8 and 1.5. Given the economic importance of H. zea, and it is extremely protein-biased p:c ratio of 4:1 relative to those reported for other lepidopterans, we decided to revisit its protein-carbohydrate regulation. Our results, using the experimental approach of the GF, show that H. zea larvae self-select a p:c ratio of 1.6:1. This p:c ratio strongly matches that of its close relative, Heliothis virescens, and is more consistent with self selected p:c ratios reported for other lepidopterans. Having accurate protein and carbohydrate regulation information for an insect herbivore pest such as H. zea is valuable for two reasons. First, it can be used to better understand feeding patterns in the field, which might lead to enhanced management. Second, it will allow researchers to develop rearing diets that more accurately reflect larval nutritional needs, which has important implications for resistance bioassays and other measures of physiological stress. PMID- 26141410 TI - Complete genome sequence and phylogenetic position of the Bacillus cereus group phage JBP901. AB - Bacteriophage JBP901, isolated from fermented food, is specific for Bacillus cereus group species and exhibits a broad host spectrum among a large number of B. cereus isolates. Genome sequence analysis revealed a linear 159,492-bp genome with overall G+C content of 39.7 mol%, and 201 ORFs. The presence of a putative methylase, the large number of tRNAs, and the large number of nucleotide metabolism- and replication-related genes in JBP901 reflects its broad lytic capacity. Most of the ORFs showed a high degree of similarity to Bcp1, Bc431v3 and BCP78, and various comparative genomics analyses also consistently clustered JBP901 with orphan (unclassified) Bacillus phages in the subfamily Spounavirinae of the family Myoviridae, supporting the presence of a distinguishable group in the subfamily. PMID- 26141411 TI - Modulation of proinflammatory NF-kappaB signaling by ectromelia virus in RAW 264.7 murine macrophages. AB - Macrophages are antigen-presenting cells (APCs) that play a crucial role in the innate immune response and may be involved in both clearance and spread of viruses. Stimulation of macrophages via Toll-like receptors (TLRs) results in activation of nuclear factor kappaB (NF-kappaB) and synthesis of proinflammatory cytokines. In this work, we show modulation of proinflammatory NF-kappaB signaling by a member of the family Poxviridae, genus Orthopoxvirus--ectromelia virus (ECTV)--in RAW 264.7 murine macrophages. ECTV interfered with p65 NF-kappaB nuclear translocation induced by TLR ligands such as lipopolysaccharide (LPS) (TLR4), polyinosinic-polycytidylic acid (poly(I:C)) (TLR3) and diacylated lipopeptide Pam2CSK4 (TLR2/6). We observed that ECTV modulates phosphorylation of Ser32 of inhibitor of kappaB (IkappaBalpha) and Ser536 of p65. Interference of ECTV with TLR signaling pathways implied that proinflammatory cytokine synthesis was inhibited. Our studies provide new insights into the strategies of proinflammatory signaling modulation by orthopoxviruses during their replication cycle in immune cells. Understanding important immune interactions between viral pathogens and APCs might contribute to the identification of drug targets and the development of vaccines. PMID- 26141412 TI - It's all in your head: sinus node dysfunction secondary to a sphenoid wing meningioma. AB - BACKGROUND: A 57-year-old man presented with recurrent episodes of dizziness, weakness of legs, and presyncope. The electrocardiogram showed a sinus bradycardia and recurrent sinus pauses. RESULTS: Cardiac evaluation revealed a normal left ventricular ejection fraction without ischemic, structural, or valvular heart disease. Pronounced limb weakness prompted neurological consultation. Cranial magnetic resonance imaging showed a large right-sided intracranial tumor adjacent to the medial sphenoid wing. Surgical removal of the tumor was accomplished successfully after application of a transient cardiac pacemaker, while decision upon permanent pacemaker implantation was postponed. Histopathology provided evidence of a meningothelial meningioma. Postoperative assessment displayed the absence of sinus node dysfunction after tumor removal. CONCLUSION: Careful differential diagnostic assessment of patients with symptomatic bradycardias needs to rule out reversible causes before implantation of permanent devices. PMID- 26141413 TI - Association of IL-8 and eNOS polymorphisms with clinical outcomes in bevacizumab treated breast cancer patients: an exploratory analysis. AB - BACKGROUND: The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients. PATIENTS AND METHODS: eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed. RESULTS: Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed. CONCLUSION: These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials. PMID- 26141414 TI - Prevalence of type-specific oncogenic human papillomavirus infection assessed by HPV E6/E7 mRNA among women with high-grade cervical lesions. AB - OBJECTIVES: Human papillomavirus (HPV) infection is a major cause of premalignant dysplasia and cervical cancer. There are no data on the prevalence of genotype specific HPV infection assessed by HPV E6/E7 mRNA in women representative of the Korean population across a broad age range. METHODS: A total of 630 women aged 17 90 years were enrolled in this study. ThinPrep liquid-based cytology samples were evaluated using the CervicGen HPV RT-qDx assay, which detects 16 high-risk (HR) HPV genotypes (set 1: HPV 16, 31, 33, 35, 52, and 58; set 2: HPV 18, 39, 45, 51, 59, and 68; and set 3: HPV 53, 56, 66, and 69). RESULTS: The overall prevalence of HPV infection was 33.2% (n=209), and oncogenic high-risk HPV was detected in 75.9% (n=107) of 141 women with high-grade cervical lesions. HPV 16 was the most common HPV genotype among women with high-grade cervical lesions and histologically confirmed cervical intraepithelial neoplasia grade 2 and above (CIN2+) in the Republic of Korea (41.6%). Among women aged over 30 years, 182/329 (55%) had invasive cervical cancer and 135 (74%) of these were infected with oncogenic HR-HPV types (in particular 25% with HPV 16). Among patients diagnosed with CIN2+, the positivity rate of HR-HPV was the highest in women aged 40-49 years. CONCLUSIONS: These results suggest that the determination of specific HPV genotypes is very important for evaluating the potential impact of preventive measures, including the use of prophylactic vaccines, on reducing the burden of cervical cancer. PMID- 26141415 TI - Clinical and molecular characteristics of multi-clone carbapenem-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in a tertiary hospital in Beijing, China. AB - OBJECTIVES: To provide the clinical and molecular characteristics of carbapenem resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae (cr-hvKP) in a tertiary hospital in Beijing, China. METHODS: The clinical characteristics of four patients with cr-hvKP isolates and 29 patients with carbapenem-resistant classic K. pneumoniae (cr-cKP) infections were analyzed retrospectively. The molecular characteristics of cr-hvKP and cr-cKP isolates were compared. RESULTS: The KPC-2 gene was detected in all cr-hvKPs except for cr-hvKP6. The cr-hvKPs belonged to three sequence types (STs; ST25, ST65, and ST11), with three pulsed field gel electrophoresis patterns (I, II, and III) and two capsular serotypes (K2 and non-typeable). Although cr-hvKP1-7 did not cause invasive clinical syndromes such as community-acquired liver abscess with or without extrahepatic complications, they were all nosocomially acquired; cr-hvKP1-5 were clones disseminated between patients A and B. Compared with cr-cKPs, pLVPK-related loci, repA, iroN, and K2 capsular serotype were more prevalent in cr-hvKPs, although no significant difference was found in clinical characteristics between patients with cr-hvKP and cr-cKP infection. CONCLUSIONS: The hypervirulent ST65 and ST25K. pneumoniae, along with carbapenem-resistant clonal populations ST11, appear to have evolved into cr-hvKP strains. The evidence of bi-directional evolution and emergence of hospital-acquired multi-clone cr-hvKP indicates a confluence of virulence and carbapenem resistance, which might pose major problems in the management of K. pneumoniae infection. PMID- 26141416 TI - Middle East Respiratory Syndrome--need for increased vigilance and watchful surveillance for MERS-CoV in sub-Saharan Africa. PMID- 26141417 TI - Severe cytomegalovirus colitis with hemolytic anemia mimicking travelers' diarrhea. AB - A case of cytomegalovirus (CMV) colitis mimicking travelers' diarrhea following short-term travel is reported. The patient was a Croatian man visiting Korea for work. He presented with fever and severe bloody diarrhea. He was diagnosed with a primary CMV infection complicated with CMV colitis and hemolytic anemia and recovered with antiviral therapy and concomitant steroid therapy. PMID- 26141418 TI - Serotype distribution, antimicrobial resistance, and molecular characterization of invasive group B Streptococcus isolates recovered from Chinese neonates. AB - BACKGROUND: Group B Streptococcus (GBS) is an important neonatal pathogen associated with high morbidity and mortality in developed countries. However, data describing neonatal GBS disease in developing countries, particularly in Asia, are largely incomplete. The aim of this study was to determine the serotype distribution, antimicrobial resistance, and molecular characteristics of invasive GBS isolates recovered from Chinese neonates. METHODS: From 2008 to 2013, 40 GBS isolates were recovered from infected neonates less than 3 months of age. All isolates were identified with the CAMP test and commercially available techniques. Serotyping was performed by latex agglutination. Antibiotic susceptibility was tested with Etest strips and the disk diffusion method. Multilocus sequence typing and erythromycin resistance gene detection (ermB and mefA) were performed by PCR. RESULTS: Four serotypes were identified. Serotype III (85%) was the most prevalent, followed by Ia (7.5%), Ib (5%), and V (2.5%). All isolates were sensitive to penicillin, ceftriaxone, and levofloxacin. However, resistance to erythromycin (92.5%), clindamycin (87.5%), and tetracycline (100%) was observed. Among erythromycin-resistant isolates, 73.0% carried the ermB gene alone, 5.4% carried the mefA gene alone, and 21.6% expressed both ermB and mefA genes. A total of seven sequence types (STs) were identified; the most prevalent was ST17, accounting for 80% of all isolates. Further, serotype III isolates contained ST17 (94.2%), ST19 (2.9%), and ST650 (2.9%). CONCLUSION: Serotype distribution, antimicrobial susceptibility, and sequence type characterization in Asia and in other global regions may contribute to improve the prevention and treatment of neonatal GBS infections. PMID- 26141419 TI - Cystic lung lesions revealing a Pneumocystis jirovecii and Aspergillus flavus co infection in an HIV-infected patient. PMID- 26141420 TI - Interleukin 35 (IL-35) and IL-37: Intestinal and peripheral expression by T and B regulatory cells in patients with Inflammatory Bowel Disease. AB - The aim of the study was to characterize and to quantify peripheral and tissue. IL-35- and IL-37-producing cells in Inflammatory Bowel Disease (IBD) patients. We studied a total of 38 active UC, 31 inactive UC, 17 active CD, and 13 inactive CD and 50 non-inflamed tissues as control group. Gene expression was measured by real time polymerase chain reaction (RT-PCR) and protein expression was evaluated in tissue by immunohistochemistry and in peripheral blood mononuclear cells by flow cytometry. Higher levels of IL-35 was produced by intestinal regulatory B cells and circulating regulatory CD4(+) and CD8(+) T cells in active vs. inactive disease or healthy donors (P<0.05). The IL-37 was conspicuously synthesized by circulating B cells, active natural killer cells and monocytes. These results suggest that down-regulation of inflammation in active IBD patients might be based on the increased expression of IL-35 and IL-37. PMID- 26141421 TI - Chemokine biomarkers in central nervous system tissue and cerebrospinal fluid in the Theiler's virus model mirror those in multiple sclerosis. AB - Chemokines have increasingly been implicated in inflammatory and infectious disease of the central nervous system, both as biomarkers and as molecules important in pathogenesis. Multiple sclerosis is a disabling disease of unknown etiology, and recently chemokines have been identified as being upregulated molecules in the disease. We were interested in how the chemokine expression patterns in the central nervous system of a viral model of multiple sclerosis, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV IDD), compared to that in humans with multiple sclerosis. Cerebrospinal fluid and spinal cord tissue were analyzed for expression of a range of cytokines and chemokines. Three chemokines, CXCL10, CXCL9, and CCL5 were strongly and specifically upregulated in both the cerebrospinal fluid and spinal cord in chronic disease, a pattern identical to that in multiple sclerosis. These data, the first study of cytokines in central nervous system tissue and cerebrospinal fluid in TMEV-IDD, support the hypothesis that multiple sclerosis is caused by chronic infection with an as-yet unidentified pathogen, possibly a picornavirus. PMID- 26141422 TI - Peripheral blood-derived cytokine gene polymorphisms and metabolic profile in women with polycystic ovary syndrome. AB - BACKGROUND: The imbalance between proinflammatory and anti-inflammatory pathways plays a role in polycystic ovary syndrome (PCOS) etiology. We aimed to investigate the relationship between polymorphisms of genes encoding inflammation associated cytokines and the metabolic profile of Brazilian women with PCOS. DESIGN: Case-control study. METHODS: The study included 196 women - 97 with PCOS (diagnosed based on Rotterdam criteria, 2003) and 99 age-matched, healthy women (controls). It was investigated polymorphisms in cytokines genes from peripheral blood-derived DNA by using PCR. RESULTS: The frequencies of alleles, genotypes, and phenotypes were similar between women with PCOS and controls. The GG genotype of the -179C/G polymorphism (IL6) was associated with higher glucose levels, while the GA and AA genotypes of the -1082A/G polymorphism (IL10), CT and TT genotypes of the -819A/T polymorphism (IL10), CA and AA genotypes of the -522A/G (IL10) polymorphism, and TA genotype of the +874T/A polymorphism (IFN-gamma) were associated with lower total cholesterol and triglycerides levels. The GA genotype of the -1082A/G polymorphism (IL10) and the CC genotype of the 10T/C polymorphism (TGF-beta1) were associated with lower and higher Ferriman indices, respectively, in women with PCOS. The AA genotype of the -1082A/G polymorphism (IL10) was associated with lower glucose levels, while the TC genotype of the 10T/C polymorphism (TGF-beta1) was associated with a lower lipid accumulation product index and higher high-density lipoprotein cholesterol levels in the PCOS group. CONCLUSIONS: The genetic polymorphisms of cytokines are not associated with PCOS development, but may contribute to common metabolic disorders associated with PCOS. PMID- 26141423 TI - Impact of temperature on feed-flow characteristics and filtration performance of an upflow anaerobic sludge blanket coupled ultrafiltration membrane treating municipal wastewater. AB - The objective of this study was to assess the operational feasibility of an anaerobic membrane bioreactor (AnMBR), consisting of an upflow anaerobic sludge blanket (UASB) reactor coupled to an ultrafiltration membrane unit, at two operational temperatures (25 degrees C and 15 degrees C) for the treatment of municipal wastewater. The results showed that membrane fouling at 15 degrees C was more severe than that at 25 degrees C. Higher chemical oxygen demand (COD) and soluble microbial products (SMP) concentrations, lower mean particle diameter, and higher turbidity in the UASB effluent at lower temperature aggravated membrane fouling compared to the 25 degrees C operation. However, the overall AnMBR treatment performance was not significantly affected by temperature, which was attributed to the physical membrane barrier. Cake resistance was found responsible for over 40% of the total fouling in both cases. However, an increase was observed in the contribution of pore blocking resistance at 15 degrees C related to the larger amount of fine particles in the UASB effluent compared to 25 degrees C. Based on the overall results, it is concluded that an AnMBR, consisting of a UASB coupled membrane unit, is not found technically feasible for the treatment of municipal wastewater at 15 degrees C, considering the rapid deterioration of the filtration performance. PMID- 26141424 TI - Enhancing the quantity and quality of short-chain fatty acids production from waste activated sludge using CaO2 as an additive. AB - The effect of calcium peroxide (CaO2) addition on anaerobic fermentation of waste activated sludge (WAS) was investigated. The lab-scale experiments were conducted at 35 degrees C with CaO2 doses ranging from 0.05 to 0.3 g/g VSS. The performances of hydrolysis and acidification of WAS were significantly enhanced by CaO2 addition, whereas the production of methane was inhibited. Maximum total short-chain fatty acids (TSCFA) production (284 mg COD/g VSS) occurred at a CaO2 dose of 0.2 g/g VSS and fermentation time of 7 d, which was 3.9 times higher than the control tests. Further, CaO2 addition led to the conversion of other SCFAs to acetic acid. Acetic acid comprised 60.2% of TSCFA with the addition of 0.2 g CaO2/g VSS compared with 45.1% in the control tests. The mechanism of improved SCFAs generation was analyzed from the view of both chemical and biological effects. Chemical effect facilitated the disintegration of WAS, and improved the activities of both hydrolytic enzymes and acid-forming enzymes. Illumina MiSeq sequencing analysis revealed that bacteria within phylum Firmicutes increased significantly due to CaO2 addition, which played an important role in the hydrolysis and acidification of WAS. In addition, CaO2 oxidized most refractory organic contaminants, which were difficult to biodegrade under the ordinary anaerobic condition. Hydroxyl radicals were the most abundant reactive oxygen species released by CaO2, which played a key role in the removal of refractory organic compounds. We developed a promising technology to produce a valuable carbon source from WAS. PMID- 26141425 TI - Water quality as a predictor of gastrointestinal illness following incidental contact water recreation. AB - Microbial measures of water quality are predictors of gastrointestinal illness among swimmers in some settings but not in others. Little is known whether water quality measures predict illness among people who engage in popular water recreation activities such as paddling, rowing, fishing, or boating ("incidental contact water recreation"). We sought to evaluate indicator microbes, protozoan pathogens, and turbidity as predictors of gastrointestinal illness following incidental contact water recreation. A cohort study of incidental contact water recreation was conducted in the Chicago, USA area. Recreation took place on inland lakes, rivers, Lake Michigan, and an urban waterway heavily impacted by wastewater effluent. Water samples were analyzed for Escherichia coli, enterococci, somatic coliphages, F+ coliphages, Giardia spp. and Cryptosporidium spp. (oo)cysts, and for turbidity. Median enterococci concentrations were 71.0 and 199.8 colony forming units/100 mL at general use and effluent-dominated waters, respectively. Among 4694 study participants with complete covariate data, 193 (4.1%) developed gastrointestinal illness within three days of water recreation. In multivariable logistic regression analysis, water quality metrics did not predict gastrointestinal illness among water recreators. Several variables other than water quality were associated acute gastrointestinal illness. The odds of such illness was increased by approximately two-fold by the presence of a chronic gastrointestinal condition, water exposure to the face, and by approximately 50% among those who fished (as opposed to other incidental contact activities). The odds of illness were reduced by approximately 50% among individuals who frequently used a water body for recreation. Unlike studies of swimmers at wastewater-impacted beaches that observed associations between water quality and illness incidence, this study did not. Public health protections for incidental contact recreation might focus on reducing exposure, particularly among fishers, those with chronic gastrointestinal conditions, and new recreators. PMID- 26141426 TI - In-situ activation of persulfate by iron filings and degradation of 1,4-dioxane. AB - Activation of persulfate by iron filings and subsequent degradation of 1,4 dioxane (dioxane) was studied in both batch-reactor and column systems to evaluate the potential of a persulfate-enhanced permeable reactive barrier (PRB) system for combined oxidative-reductive removal of organic contaminants from groundwater. In batch experiments, decomposition of persulfate to sulfate and degradation of dioxane both occurred rapidly in the presence of iron filings. Conversely, dioxane degradation by persulfate was considerably slower in the absence of iron filings. For the column experiments, decomposition and retardation of persulfate was observed for transport in the columns packed with iron filings, whereas no decomposition or retardation was observed for transport in columns packed with a reference quartz sand. Both sulfate production and dioxane degradation were observed for the iron-filings columns, but not for the sand column. The pH of the column effluent increased temporarily before persulfate breakthrough, and significant increases in both ferrous and ferric iron coincided with persulfate breakthrough. Multiple species of free radicals were produced from persulfate activation as determined by electron paramagnetic resonance (EPR) spectroscopy. The impact of the oxidation process on solution composition and iron-filings surface chemistry was examined using ICP-MS, SEM EDS, and XRD analyses. A two-stage reaction mechanism is proposed to describe the oxidation process, consisting of a first stage of rapid, solution-based, radical driven decomposition of dioxane and a second stage governed by rate-limited surface reaction. The results of this study show successful persulfate activation using iron filings, and the potential to apply an enhanced PRB method for improving in-situ removal of organic contaminants from groundwater. PMID- 26141427 TI - Characterising organic matter in recirculating aquaculture systems with fluorescence EEM spectroscopy. AB - The potential of recirculating aquaculture systems (RAS) in the aquaculture industry is increasingly being acknowledged. Along with intensified application, the need to better characterise and understand the accumulated dissolved organic matter (DOM) within these systems increases. Mature RASs, stocked with rainbow trout and operated at steady state at four feed loadings, were analysed by dissolved organic carbon (DOC) analysis and fluorescence excitation-emission matrix (EEM) spectroscopy. The fluorescence dataset was then decomposed by PARAFAC analysis using the drEEM toolbox. This revealed that the fluorescence character of the RAS water could be represented by five components, of which four have previously been identified in fresh water, coastal marine water, wetlands and drinking water. The fluorescence components as well as the DOC showed positive correlations with feed loading, however there was considerable variation between the five fluorescence components with respect to the degree of accumulation with feed loading. The five components were found to originate from three sources: the feed; the influent tap water (groundwater); and processes related to the fish and the water treatment system. This paper details the first application of fluorescence EEM spectroscopy to assess DOM in RAS, and highlights the potential applications of this technique within future RAS management strategies. PMID- 26141428 TI - Direct ultrafiltration performance and membrane integrity monitoring by microbiological analysis. AB - The feasibility of substituting a conventional pre-treatment, consisting of dioxi chlorination, coagulation/flocculation, settling and sand filtration, of a drinking water treatment plant (DWTP) by direct ultrafiltration (UF) has been assessed from a microbiological standpoint. Bacterial indicators, viral indicators and human viruses have been monitored in raw river, ultrafiltered and conventionally pre-treated water samples during two years. Direct UF has proven to remove bacterial indicators quite efficiently and to a greater extent than the conventional process does. Nevertheless, the removal of small viruses such as some small bacteriophages and human viruses (e.g. enteroviruses and noroviruses) is lower than the current conventional pre-treatment. Membrane integrity has been assessed during two years by means of tailored tests based on bacteriophages with different properties (MS-2, GA and PDR-1) and bacterial spores (Bacillus spores). Membrane integrity has not been compromised despite the challenging conditions faced by directly treating raw river water. Bacteriophage PDR-1 appears as a suitable microbe to test membrane integrity, as its size is slightly larger than the considered membrane pore size. However, its implementation at full scale plant is still challenging due to difficulties in obtaining enough phages for its seeding. PMID- 26141429 TI - [Entomological factors of arboviruses emergences]. AB - Arboviruses - viruses transmitted by haematophagous arthropods - are responsible for febrile syndromes, which sometimes include haemorrhagic or neurological symptoms. Human activities have facilitated the emergence of these originally zoonotic viruses and the domestication and spread throughout the world of their major vectors. The last decade has seen significant changes in the epidemiology of arboviruses transmitted by mosquitoes of the genus Aedes, particularly in relation to the intercontinental spread of Aedes albopictus. Here, we address the epidemiological consequences of the invasion by this species into Central Africa and Europe in a context of viral globalization. The risk of transmission in these areas is influenced by virus-vector adaptation phenomena as well as environmental phenomena including climate. Faced with these new risks, it is essential to develop competences in entomological and virological surveillance, risk assessment and forecasting of epidemic risk in order to develop strategies for the prevention and control of epidemics. PMID- 26141430 TI - Editorial overview: Motor circuits and action. PMID- 26141431 TI - Abstracts from the Twentieth Annual Education Conference of the National Society of Genetic Counselors (Washington, DC, November 2001). PMID- 26141432 TI - Population identification and divergence threshold in Psoroptidae based on ribosomal ITS2 and mitochondrial COI genes. AB - Psoroptidae mites are a type of small mites with a wide range of hosts. The proliferation of Psoroptidae mites could cause symptoms such as severe itching, atopic dermatitis, and hair loss in infected animals. If severely infected, death can also occur. The morphological classification and identification of Psoroptidae mites is problematic due to the overlapping geographical distribution. In addition, there is no divergence threshold for molecular classification and identification. To solve this problem, gDNA was extracted from individual Psoroptes and Otodectes mites (China) for amplification of rDNA ITS2 and mtDNA COI. After that, the sequences obtained were aligned and analyzed with those retrieved from GenBank. Based on rDNA ITS2 sequences, Psoroptidae was divided into three genera, namely, Psoroptes, Chorioptes, and Otodectes, which was in accordance with morphological classification. The intraspecies, interspecies, and intergenera could be differentiated effectively, with thresholds <= 5.20, 6.18-14.86, and >=15.72 %, respectively. However, based on mtDNA COI sequences, Psoroptidae was divided into four genera with Caparinia added, as Caparinia sp did not cluster with the other three genera. The intra- and interspecies could be differentiated effectively, but interspecies and intergenera could not. The intra- and interspecies identification thresholds were <= 2.12 and >=10.93 %. Further analysis showed that host but not geographical isolation was found in Psoroptes and Chorioptes, whereas Otodectes mites parasitizing dogs and cats were the same species; neither host nor geographical isolation was observed. In conclusion, rDNA ITS2 is better than mtDNA COI for DNA barcoding in Psoroptidae. PMID- 26141433 TI - Macroparasites of allis shad (Alosa alosa) and twaite shad (Alosa fallax) of the Western Iberian Peninsula Rivers: ecological, phylogenetic and zoonotic insights. AB - Samples of anadromous Alosa alosa (Clupeidae) (n = 163) and Alosa fallax (Clupeidae) (n = 223), caught in Western Iberian Peninsula Rivers from 2008 to 2013, were examined for buccal, branchial and internal macroparasites, which were identified using morphological and molecular methods. Alosa alosa were infected with Anisakis simplex s.s., Anisakis pegreffii, Hysterothylacium aduncum, Rhadinorhynchus pristis, Mazocraes alosae, Hemiurus appendiculatus, Ceratothoa italica and an unidentified ergasilid copepod. Ceratothoa italica represents a new host record for A. alosa. Alosa fallax were infected with A. simplex s.s., A. pegreffii, H. aduncum, H. appendiculatus, Clavellisa emarginata and an unidentified cymothoid isopod. This is the first report of C. italica, C. emarginata and M. alosae in the Iberian Peninsula. The phylogenetic positions of M. alosae, H. appendiculatus and C. emarginata were assessed using 18S and 28S ribosomal RNA (rRNA); our contributions provide a better understanding of the phylogenetic relationships within their groups. Qualitative and quantitative differences in the parasite faunas of these two shad species are consistent with different feeding strategies. The results provide information about host migration behaviour and transmission pathways through diet during the marine trophic phase of the shad's life cycle and their roles as paratenic or final hosts and transporters of parasites between seawater and freshwater environments. The zoonotic parasites A. simplex s.s. and A. pegreffii pose a risk for consumers or riverine mammals (e.g. European otter). The use of parasites as biological tags for shad stocks in Western Iberian Rivers could be a useful approach in multidisciplinary studies concerning fish stock delimitation and characterization. PMID- 26141434 TI - Intraspecific variation of body size in a gamasid mite Laelaps clethrionomydis: environment, geography and host dependence. AB - We investigated intraspecific variation in body size of an ectoparasitic gamasid mite, Laelaps clethrionomydis, across 12 localities in the Palearctic. We asked whether mites collected from the same host species in different localities or from different host species in the same locality vary in body size. Within host species, mites collected in different localities differed significantly in body size, tending to be larger in northern than in southern localities. In addition, mite body size correlated negatively with mean annual temperature in a locality. Mites collected from different hosts in the same locality differed significantly in body size when hosts belonged to different genera but did not differ when collected from congeneric hosts. We conclude that intraspecific variation in mite body size is caused by interplay of environmental and host-related factors. PMID- 26141435 TI - Resveratrol- and alpha-viniferin-induced alterations of acetylcholinesterase and nitric oxide synthase in Raillietina echinobothrida. AB - Phytostilbenes, like resveratrol and alpha-viniferin, which occur mainly in the plants and belong to the families Cyperaceae, Vitaceae, and Gnetaceae are extensively popular for their medicinal and nutritional properties. In Northeast India, the Jaintia tribes consume these phytochemicals through aqueous extract of the medicinal plant Carex baccans to control helminthiasis. The present study aimed to investigate the inhibitory effect of the phytochemicals on neurotransmitters and its related enzymes in helminth parasite Raillietina echinobothrida. Viability of the parasites exposed to the phytostilbenes and extent of inhibition of cholinergic and nitrergic enzymes were evaluated in comparison to reference anthelmintic drug praziquantel and two known enzyme inhibitors, namely Nomega-nitro-L-arginine and pyridostigmine. On exposure to resveratrol, alpha-viniferin, and reference drug praziquantel, the parasites ceased movement at 9.37, 11.38, and 0.24 h followed by death at 23.65, 34.13, and 1.87 h, respectively. Exposed parasites also showed a significant decrease in the activity of acetylcholinesterase (46.101, 65.935, and 63.645%) and nitric oxide synthase (61.241, 55.046, and 29.618%) in comparison to the controls. In addition, a decreased trend in nitric oxide (NO) level was also detected in the tissue of different phytochemical-exposed parasites compared to control. The present study suggests that anthelmintic potential of both the phytochemicals is mediated through inhibition of two vital enzymes which play diverse role in intracellular communications through neuromuscular system. PMID- 26141436 TI - MIC3, a novel cross-protective antigen expressed in Toxoplasma gondii and Neospora caninum. AB - Microneme protein 3 (MIC3) is an important adhesion molecule expressed by Toxoplasma gondii and Neospora caninum that plays a crucial role in invasion. In our study, we found that recombinant TgMIC3 (rTgMIC3) was recognized by both T. gondii-reactive sera and hyper-immune serum against N. caninum. Polyclonal antibodies against TgMIC3 reacted with N. caninum by western blot and immunofluorescence assay (IFA). These results indicate that MIC3 is a novel cross reactive antigen expressed in N. caninum and T. gondii. To evaluate the immune protective effect of TgMIC3, we created the eukaryotic expression vector pcDNA3.1 TgMIC3, transfected this vector into HEK293T cells by lipofection, and evaluated TgMIC3 expression in HEK293T cells using western blot and IFA. Then, groups of BALB/c mice were immunized with recombinant TgMIC3 protein, pcDNA3.1-TgMIC3, or two-vaccine immunization. The mice were challenged with T. gondii RH or N. caninum Nc-1 tachyzoites 14 days after the final immunization. The survival time of T. gondii-infected mice was recorded, and the parasite burden in the brain of N. caninum-infected mice 30 days post-infection was measured using real-time PCR. The results demonstrated that mice immunized with TgMIC3-based vaccines elicited high antibody titers. After parasitic challenge, mice immunized with pcDNA-TgMIC3 exhibited prolonged survival when infected with T. gondii tachyzoites and a lower parasitic burden in the brains of mice challenged with N. caninum tachyzoites. These results demonstrate that TgMIC3 is a cross-protective antigen expressed in T. gondii and N. caninum and could elicit some protection against toxoplasmosis and neosporosis. PMID- 26141437 TI - Comparative study of antibody immobilization mediated by lipid and polymer fibers. AB - Antibody immobilization and function retention are important to a variety of applications, including proteomics, drug discovery, diagnostics, and biosensors. The present study investigates antibody immobilization mediated by cholesteryl succinyl silane (CSS) fibers, in comparison to hydrophobic polycaprolactone (PCL) fibers and hydrophilic plasma-treated PCL fibers. When incubated with a model protein, the formation of protein aggregates is observed on hydrophobic PCL fibers but not on the more hydrophobic CSS fibers, indicating that CSS fibers immobilize proteins through mechanisms other than hydrophobic interaction. When exposed to a limited amount of antibody, CSS fibers immobilize more antibodies than plasma-treated PCL fibers and no fewer antibodies than PCL fibers. The function retention of antibodies immobilized on the fibers is analyzed using a cell-capture assay, which shows that the antibody-functionalized CSS fibrous matrices capture 6- or 7-fold more cells than the antibody-functionalized PCL or plasma-treated PCL fibrous matrices, respectively. Data collected from the study show that the lipid fiber-mediated immobilization of antibody not only maintains the advantages of physical immobilization such as easiness and rapidness of operation but also improves function retention. PMID- 26141438 TI - Physical factors affecting chloroquine binding to melanin. AB - Chloroquine is an antimalarial drug but is also prescribed for conditions such as rheumatoid arthritis. Long-term users risk toxic side effects, including retinopathy, thought to be caused by chloroquine accumulation on ocular melanin. Although the binding potential of chloroquine to melanin has been investigated previously, our study is the first to demonstrate clear links between chloroquine adsorption by melanin and system factors including temperature, pH, melanin type, and particle size. In the current work, two Sepia melanins were compared with bovine eye as a representative mammalian melanin. Increasing the surface anionic character due to a pH change from 4.7 to 7.4 increased each melanin's affinity for chloroquine. Although the chloroquine isotherms exhibited an apparently strong interaction with each melanin, isosteric heat analysis indicated a competitive interaction. Buffer solution cations competed effectively at low surface coverage; chloroquine adsorption occurs via buffer cation displacement and is promoted by temperature-influenced secondary structure swelling. PMID- 26141439 TI - AFM of self-assembled lambda DNA-histone networks. AB - Atomic force microscopy (AFM) was used to investigate the self-assembly behavior of lambda-DNA and histones at varying histone:DNA ratios. Without histones and at the lowest histone:DNA ratio (less than one histone per 1000 base pairs of DNA), the DNA appeared as individual (uncomplexed), double-stranded DNA molecules. At increasing histone concentrations (one histone per 500, 250 and 167 base pairs of DNA), the DNA molecules started to form extensive polygonal networks of mostly pentagons and hexagons. The observed networks might be one of the naturally occurring, stable DNA-histone structures. The condensing effects of the divalent cations Mg(2+) and Ca(2+) on the DNA-histone complexes were also investigated. The networks persisted at high Mg(2+) concentration (20mM) and the highest histone concentration. At high Ca(2+) concentration and the highest histone concentration, the polygonal network disappeared and, instead, individual, tightly condensed aggregates were formed. PMID- 26141440 TI - The AALAS Journals: 2014 in Review. PMID- 26141441 TI - Comparison of Cesium-137 and X-ray Irradiators by Using Bone Marrow Transplant Reconstitution in C57BL/6J Mice. AB - Mice are used extensively in transplantation studies involving bone marrow ablation. Due to the increasing security issues and expenses involved with gamma irradiators, self-contained X-ray irradiators have been increasing in popularity. We hypothesized that bone marrow ablation by irradiation of mice with a (137)Cs irradiator would be comparable to that from an X-ray source irradiator. A lethal dose curve was obtained by irradiating C57BL/6J mice with 500, 700, 900, and 1100 cGy from either source. These data were used to determine the lethal radiation exposure range for a noncompetitive bone marrow engraftment curve for each source. At 90 d after reconstitution, the bone marrow engraftment curves revealed significant differences between the 2 sources in the establishment of B cell, myeloid, and T cell lineages. Murine B cell reconstitution after exposure to a (137)Cs source was greater than that after X-ray exposure at each dose level, whereas the converse was true for myeloid cell reconstitution. At the 1050- and 1100-cGy doses, mice irradiated by using the X-ray source demonstrated higher levels of T cell reconstitution but decreased survival compared with mice irradiated with the (137)Cs source. We concluded that although both sources ablated endogenous bone marrow sufficiently to enable stem cell engraftment, there are distinct physiologic responses that should be considered when choosing the optimal source for use in a study and that irradiation from the (137)Cs source was associated with lower overall morbidity due to opportunistic infection. PMID- 26141442 TI - Effects of Sleep Fragmentation and Chronic Latent Viral Infection on Behavior and Inflammation in Mice. AB - Many chronic diseases are associated with both fatigue and disrupted or nonrestorative sleep. In addition, so-called 'sickness behaviors' (for example, anorexia, anhedonia, reduced social interaction, fatigue) are common during infectious and inflammatory disease and have been linked to facets of the immune response. To study these relationships, we used murine gammaherpesvirus (MuGHV), a natural pathogen of wild rodents that provides an experimental model for studying the pathophysiology of an Epstein-Barr (EBV)-like gamma-herpesvirus infection in mice. We exposed male and female C57BL/6J mice that were either uninfected or latently infected with MuGHV to either sleep fragmentation (SF) or control conditions and measured the effects on behavior and markers of inflammation. Exposure of infected male mice to SF during the normal somnolent (light) phase significantly reduced locomotor activity during the subsequent active phase, despite an intervening 6-h rest period. Infection was associated with significant increases in lung IFNgamma and CXC motif ligand (CXCL) 10 in both male and female mice. In both infected and uninfected male mice, exposure to SF was associated with lower levels of IL1beta and C-C motif ligand (CCL) 3 in lung. Exposure of infected female mice to SF led to reductions in lung IL2, CXCL1, and CCL 3. Thus, compared with control conditions, SF was generally associated with lower concentrations of various cytokines in lung. These findings, together with our previous work, indicate that complex interactions among several host factors likely contribute to the behavioral and inflammatory changes associated with viral infection and sleep disruption even in a well controlled mouse model. PMID- 26141443 TI - A Novel alpha-Hemolytic Streptococcus Species (Streptococcus azizii sp. nov.) Associated with Meningoencephalitis in Naive Weanling C57BL/6 Mice. AB - During 1 year, experimentally naive C57BL/6NCrl weanlings born to timed-pregnant dams from a single vendor demonstrated markedly increased mortality associated with runting, abnormal gait, and decreased activity. Gram-positive, aerobic, alpha-hemolytic, coccoid bacteria were isolated from the meninges (n = 16), blood (n = 1), and kidneys (n = 1) of clinically affected weanlings (n = 15); from the uterus (n = 1), meninges (n = 1), and oral cavity (n = 2) of 3 dams; and from the meninges and oral cavity of a clinically affected 86-d-old mouse in the same colony. Multifocal, necrosuppurative meningoencephalitis and ventriculitis with intralesional gram-positive coccoid bacteria were present in all but 2 affected animals. The bacterium also was isolated from the oral cavity of an asymptomatic timed-pregnant dam (1 of 23) from the same vendor and from 8 mice at the vendor's facility. All isolates (n = 25) were identified by using 2 semiautomated rapid identification systems, one of which consistently identified the causative bacterium as Aerococcus viridans 2 (n = 12) or 3 (n = 13), with probabilities of 55.7% to 98.3%. The bacterium did not grow in 6.5% NaCl at 10 degrees C, thus suggesting a Streptococcus species. Partial 16S rRNA sequencing of 4 isolates suggested S. hyointestinalis (probability, 93.4%) and S. gallinaceus (99.5%). Full 16S rRNA sequences for 3 isolates identified the bacterium as a novel Streptococcus species most closely related to S. acidominimus strain LGM (96.5%) and Streptococcus species strain Smarlab 3301444 (96.3%) and for which we propose the name S. azizii. PMID- 26141444 TI - Determination of RBC Survival in C57BL/6 and C57BL/6-Tg(UBC-GFP) Mice. AB - Although several methods for determining erythrocyte lifespan are used in research studies that involve mice, all involve the alteration of RBC to allow for its tracking over time, which may affect overall RBC survival. The aims of this study were to determine 1) whether sex affects RBC survival; 2) whether RBC survival differs between the biotin method and an alternative method that uses GFP; and 3) whether repeat exposure of mice to biotin results in an antibiotin antibody response or decreased RBC survival. The results suggest no difference in the RBC half-life between male and female C57BL/6 mice (22.9 +/- 1.2 and 22.4 +/- 0.9 d, respectively). In addition, RBC half-life did not differ between the biotin- and GFP-based methods (20.5 +/- 2.1 d and 22.7 +/- 2.1 d, respectively). Finally, retransfusion of mice 90 d after an initial transfusion with biotin labeled RBC did not induce detectable antibiotin antibodies nor alter the half life of transfused biotin-labeled RBC (initial transfusion, 22.0 +/- 1.2 d; subsequent transfusion, 23.4 +/- 1.4 d, respectively). PMID- 26141445 TI - The Effects of Acute Blood Loss for Diagnostic Bloodwork and Fluid Replacement in Clinically Ill Mice. AB - Despite the great value of diagnostic bloodwork for identifying disease in animals, the volume of blood required for these analyses limits its use in laboratory mice, particularly when they are clinically ill. We sought to determine the effects of acute blood loss (ABL) following blood collection for diagnostic bloodwork in healthy mice compared with streptozotocin-induced diabetic and dextran sulfate sodium (DSS)-treated dehydrated mice. ABL caused several mild changes in the control mice, with significant decreases in body weight, temperature, and activity in both experimental groups; increased dehydration and azotemia in the DSS-treated mice; and a significant drop in the blood pressure of the diabetic mice. To determine whether these negative outcomes could be ameliorated, we treated mice with intraperitoneal lactated Ringers solution either immediately after or 30 min before ABL. Notably, preABL administration of fluids helped prevent the worsening of the dehydration and azotemia in the DSS-treated mice and the changes in blood pressure in the diabetic mice. However, fluid administration provided no benefit in control of blood pressure when administered after ABL in the diabetic mice. Furthermore, fluid therapy did not prevent ABL-induced drops in body weight and activity. Although one mouse not receiving fluid therapy became moribund at the 24-h time point, no animals died during the 24-h study. This investigation demonstrates that blood for diagnostic bloodwork can be collected safely from clinically ill mice and that preemptive fluid therapy mitigates some of the negative changes associated with this blood loss. PMID- 26141446 TI - Optical Coherence Tomography of Pulmonary Arterial Walls in Humans and Pigs (Sus scrofa domesticus). AB - Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by progressive elevation of the pulmonary pressures that, in the absence of therapy, results in chronic right-heart failure and premature death. The vascular pathology of PAH is characterized by progressive loss of small (diameter, less than 50 MUm) peripheral pulmonary arteries along with abnormal medial thickening, neointimal formation, and intraluminal narrowing of the remaining pulmonary arteries. Vascular pathology correlates with disease severity, given that hemodynamic effects and disease outcomes are worse in patients with advanced compared with lower-grade lesions. Novel imaging tools are urgently needed that demonstrate the extent of vascular remodeling in PAH patients during diagnosis and treatment monitoring. Optical coherence tomography (OCT) is a catheter-based intravascular imaging technique used to obtain high-resolution 2D and 3D cross sectional images of coronary arteries, thus revealing the extent of vascular wall pathology due to diseases such as atherosclerosis and in-stent restenosis; its utility as a diagnostic tool in the assessment of the pulmonary circulation is unknown. Here we show that OCT provides high-definition images that capture the morphology of pulmonary arterial walls in explanted human lungs and during pulmonary arterial catheterization of an adult pig. We conclude that OCT may facilitate the evaluation of patients with PAH by disclosing the degree of wall remodeling present in pulmonary vessels. Future studies are warranted to determine whether this information complements the hemodynamic and functional assessments routinely performed in PAH patients, facilitates treatment selection, and improves estimates of prognosis and outcome. PMID- 26141447 TI - Validation of Respiratory Inductance Plethysmography for Measuring Tidal Volume in Swine. AB - Measuring tidal volume (VT) in nonintubated swine or swine with leaking breathing circuits is challenging. The aim of this study was to validate respiratory inductance plethysmography (RIP) for measuring VT in swine that are comparable in size to adult humans. To determine calibration curves, VT and RIP readings were obtained from anesthetized swine (n = 8; weight, 46-50 kg) during positive pressure (mechanical) ventilation and spontaneous breathing. For positive pressure ventilation, 6 pigs were mechanically ventilated by using the pressure control mode. The 2 pigs in the spontaneously breathing cohort each received a single intravenous bolus dose of propofol to abolish spontaneous breathing; VT was measured during gradual return of their respiratory drive. A flow-volume sensor was placed between the proximal end of the endotracheal tube and breathing circuit for the recording of inspiratory and expiratory VT. RIP readings were recorded by using 2 bands, which simultaneously measured ribcage and abdominal excursions. The data revealed that VT was linearly correlated with the movements of both ribcage and abdomen as measured by using plethysmography over a large range of tidal volume (44 to 1065 mL). In addition, the intercept of the linear equation was small or even negative during spontaneous breathing but increased significantly (maximum, 145 mL, 59.2 +/- 35.1 mL) during positive pressure ventilation. Our results indicate that VT in swine can be calculated by using a simple univariate linear regression equation with RIP readings obtained during either mechanical ventilation or spontaneous breathing. PMID- 26141448 TI - Endemic Viruses of Squirrel Monkeys (Saimiri spp.). AB - Nonhuman primates are the experimental animals of choice for the study of many human diseases. As such, it is important to understand that endemic viruses of primates can potentially affect the design, methods, and results of biomedical studies designed to model human disease. Here we review the viruses known to be endemic in squirrel monkeys (Saimiri spp.). The pathogenic potential of these viruses in squirrel monkeys that undergo experimental manipulation remains largely unexplored but may have implications regarding the use of squirrel monkeys in biomedical research. PMID- 26141450 TI - Use of Femoral Head and Neck Ostectomy and Physical Therapy to Manage Osteoarthritis in a Rhesus Macaque (Macaca mulatta). AB - Osteoarthritis is associated with pain and immobility in both humans and animals. However, available resources for osteoarthritis management in captive NHP are limited. This case report describes a novel management strategy for a 10-y-old male macaque with unilateral hindlimb lameness, prominent muscle wasting, and severely limited range of motion. Radiographs of the affected limb showed lytic lesions of the femoral head. To relieve pain and improve mobility, femoral head and neck ostectomy (FHO) was performed, and multiple pharmacotherapies were initiated. The macaque also received a unique method of physical therapy that required no sedation, acted as enrichment, and was implemented by using a conventional caging system. The response to therapy was monitored by measuring thigh circumference in the operated and nonoperated limbs, which demonstrated improvement in both legs. The unique physical therapy in conjunction with surgery and pharmacotherapy benefited the macaque with osteoarthritis by reducing discomfort and improving mobility. PMID- 26141449 TI - A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the 'Animal Rule'. AB - Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the 'Animal Rule,' through which demonstration of the efficacy of a product can be 'based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.' This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops). PMID- 26141451 TI - Self-Injurious Behavior Secondary to Cytomegalovirus-Induced Neuropathy in an SIV Infected Rhesus Macaque (Macaca mulatta). AB - A 3.5-y-old, female rhesus macaque (Macaca mulatta) inoculated with SIVmac239 presented 8 mo later for inappetence and facial bruising. Physical examination revealed a superficial skin abrasion below the left eye, bruising below the left brow, and epistaxis of the left nostril. There were no significant findings on CBC, serum chemistry, urinalysis, or radiographs. Differential diagnoses included infectious etiologies, self-injurious behavior, immune-mediated dermatitis, and neoplasia. Lack of response to antibiotic and analgesic therapy and observations of the macaque made it apparent that the skin lesions were self-inflicted. The excoriations rapidly progressed to extend over the nose, and the left palpebrae became edematous. Euthanasia was elected because the macaque appeared to be experiencing continued discomfort despite analgesic therapy. Histopathologic examination revealed systemic cytomegalovirus (CMV) infection involving the facial nerves, periocular nerves, meninges, and perimesenteric lymph nodes. CMV is a common infection in macaques, with adult seroprevalence close to 100% in most colonies. Infection in immunocompetent animals is usually asymptomatic but can cause significant clinical disease in immunodeficient hosts. CMV is associated with a painful peripheral neuropathy in human AIDS patients, and analgesic treatment is often unsatisfactory. Peripheral neuropathy secondary to CMV should be considered as an underlying cause of self-injurious behavior in SIV infected macaques. Macaques affected by other diseases and disorders may also be at risk for development of painful peripheral neuropathies. PMID- 26141452 TI - Severe Acquired Idiopathic Thrombocytopenia in a Female Cynomolgus Macaque (Macaca fascicularis). AB - A 4-y-old female cynomolgus macaque presented for veterinary evaluation prior to placement in a preclinical study showed markedly low platelet counts that continued to decrease over time. Physical examination over the next several days showed areas of pale red discoloration in forelimbs, anterior thorax, and inguinal area and multifocal pinpoint areas of erythema or scabs. An area of dark red discoloration approximately 2 cm in diameter on the dorsal surface of the tongue was discovered on day 9. The macaque was euthanized, and histopathologic evaluation showed multifocal, ulcerative or erosive, hemorrhagic, lymphohistiocytic and neutrophilic glossitis and tonsillitis. The lesions on the tongue were associated with opportunistic fungi consistent with Candida albicans. The bone marrow showed megakaryocytic hyperplasia. There was no evidence of increased consumption of platelets, sequestration of platelets, or bone marrow suppression. The monkey was serologically negative for simian retrovirus, SIV, and simian T-lymphotropic virus. In light of cases reported in humans, immune mediated destruction of platelets due to autoantibodies secondary to Candida albicans infection was considered. However, we were unable to detect antiplatelet antibodies on the platelet surface or in serum to support this etiology; therefore idiopathic thrombocytopenia was diagnosed. To our knowledge, this case represents the second reported observation of acquired thrombocytopenia in a nonhuman primate and the first reported observation in a cynomolgus macaque. PMID- 26141453 TI - Toward universal coverage in Afghanistan: A multi-stakeholder assessment of capacity investments in the community health worker system. AB - Global efforts to scale-up the community health workforce have accelerated as a result of the growing evidence of their effectiveness to enhance coverage and health outcomes. Reconstruction efforts in Afghanistan integrated capacity investments for community based service delivery, including the deployment of over 28,000 community health workers (CHWs) to ensure access to basic preventive and curative services. The study aimed to conduct capacity assessments of the CHW system and determine stakeholder perspectives of CHW performance. Structured interviews were conducted on a national sample from 33 provinces and included supervisors, facility providers, patients, and CHWs. Formative assessments were also conducted with national policymakers, community members and health councils in two provinces. Results indicate that more than 70% of the NGO's provide comprehensive training for CHWs, 95% CHWs reported regular supervision, and more than 60% of the health posts had adequate infrastructure and essential commodities. Innovative strategies of paired male and female CHWs, institution of a special cadre of community health supervisors, and community health councils were introduced as systems strengthening mechanisms. Reported barriers included unrealistic and expanding task expectations (14%), unsatisfactory compensation mechanisms (75%), inadequate transport (69%), and lack of commodities (40%). Formative assessments evidenced that CHWs were highly valued as they provided equitable, accessible and affordable 24-h care. Their loyalty, dedication and the ability for women to access care without male family escorts was appreciated by communities. With rising concerns of workforce deficits, insecurity and budget constraints, the health system must enhance the capacity of these frontline workers to improve the continuum of care. The study provides critical insight into the strengths and constraints of Afghanistan's CHW system, warranting further efforts to contextualize service delivery and mechanisms for their support and motivation. PMID- 26141454 TI - Prediction of hydrogen and carbon chemical shifts from RNA using database mining and support vector regression. AB - The Biological Magnetic Resonance Data Bank (BMRB) contains NMR chemical shift depositions for over 200 RNAs and RNA-containing complexes. We have analyzed the (1)H NMR and (13)C chemical shifts reported for non-exchangeable protons of 187 of these RNAs. Software was developed that downloads BMRB datasets and corresponding PDB structure files, and then generates residue-specific attributes based on the calculated secondary structure. Attributes represent properties present in each sequential stretch of five adjacent residues and include variables such as nucleotide type, base-pair presence and type, and tetraloop types. Attributes and (1)H and (13)C NMR chemical shifts of the central nucleotide are then used as input to train a predictive model using support vector regression. These models can then be used to predict shifts for new sequences. The new software tools, available as stand-alone scripts or integrated into the NMR visualization and analysis program NMRViewJ, should facilitate NMR assignment and/or validation of RNA (1)H and (13)C chemical shifts. In addition, our findings enabled the re-calibration a ring-current shift model using published NMR chemical shifts and high-resolution X-ray structural data as guides. PMID- 26141455 TI - Abstracts from the Twenty-Second Annual Education Conference of the National Society of Genetic Counselors (Charlotte, NC, September 2003). PMID- 26141457 TI - Nuclear basic fibroblast growth factor regulates triple-negative breast cancer chemo-resistance. AB - INTRODUCTION: Chemotherapy remains the only available treatment for triple negative (TN) breast cancer, and most patients exhibit an incomplete pathologic response. Half of patients exhibiting an incomplete pathologic response die within five years of treatment due to chemo-resistant, recurrent tumor growth. Defining molecules responsible for TN breast cancer chemo-resistance is crucial for developing effective combination therapies blocking tumor recurrence. Historically, chemo-resistance studies have relied on long-term chemotherapy selection models that drive genetic mutations conferring cell survival. Other models suggest that tumors are heterogeneous, being composed of both chemo sensitive and chemo-resistant tumor cell populations. We previously described a short-term chemotherapy treatment model that enriches for chemo-residual TN tumor cells. In the current work, we use this enrichment strategy to identify a novel determinant of TN breast cancer chemotherapy resistance [a nuclear isoform of basic fibroblast growth factor (bFGF)]. METHODS: Studies are conducted using our in vitro model of chemotherapy resistance. Short-term chemotherapy treatment enriches for a chemo-residual TN subpopulation that over time resumes proliferation. By western blotting and real-time polymerase chain reaction, we show that this chemotherapy-enriched tumor cell subpopulation expresses nuclear bFGF. The importance of bFGF for survival of these chemo-residual cells is interrogated using short hairpin knockdown strategies. DNA repair capability is assessed by comet assay. Immunohistochemistry (IHC) is used to determine nuclear bFGF expression in TN breast cancer cases pre- and post- neoadjuvant chemotherapy. RESULTS: TN tumor cells surviving short-term chemotherapy treatment express increased nuclear bFGF. bFGF knockdown reduces the number of chemo residual TN tumor cells. Adding back a nuclear bFGF construct to bFGF knockdown cells restores their chemo-resistance. Nuclear bFGF-mediated chemo-resistance is associated with increased DNA-dependent protein kinase (DNA-PK) expression and accelerated DNA repair. In fifty-six percent of matched TN breast cancer cases, percent nuclear bFGF-positive tumor cells either increases or remains the same post- neoadjuvant chemotherapy treatment (compared to pre-treatment). These data indicate that in a subset of TN breast cancers, chemotherapy enriches for nuclear bFGF-expressing tumor cells. CONCLUSION: These studies identify nuclear bFGF as a protein in a subset of TN breast cancers that likely contributes to drug resistance following standard chemotherapy treatment. PMID- 26141458 TI - Primary care characteristics and stage of cancer at diagnosis using data from the national cancer registration service, quality outcomes framework and general practice information. AB - BACKGROUND: Survival from cancer is worse in England than in some European countries. To improve survival, strategies in England have focused on early presentation (reducing delay to improve stage at diagnosis), improving quality of care and ensuring equity throughout the patient pathway. We assessed whether primary care characteristics were associated with later stage cancer at diagnosis (stages 3/4 versus 1/2) for female breast, lung, colorectal and prostate cancer. METHODS: Data obtained from the National Cancer Registration Service, Quality Outcomes Framework, GP survey and GP workforce census, linked by practice code. Risk differences (RD) were calculated by primary care characteristics using a generalised linear model, accounting for patient clustering within practices. Models were adjusted for age, sex and an area-based deprivation measure. RESULTS: For female breast cancer, being with a practice with a higher two week wait (TWW) referral rate (RD -1.8% (95 % CI -0.5% to -3.2%) p = 0.003) and a higher TWW detection rate (RD -1.7% (95 % CI -0.3% to -3.0%) p = 0.003) was associated with a lower proportion diagnosed later. Being at a practice where people thought it less easy to book at appointment was associated with a higher percentage diagnosed later (RD 1.8% (95 % CI 0.2% to 3.4%) p = 0.03). For lung cancer, being at practices with higher TWW referral rates was associated with lower proportion advanced (RD-3.6% (95 % CI -1.8%, -5.5%) p < 0.001) whereas being at practices with more patients per GP was associated with higher proportion advanced (RD1.8% (95 % CI 0.2, 3.4) p = 0.01). A higher rate of gastrointestinal investigations was associated with a lower proportion of later stage colorectal cancers (RD 2.0% (95 % CI -0.6% to -3.6%) p = 0.01). No organisational characteristics were associated with prostate cancer stage. CONCLUSION: Easier access to primary care, faster referral and more investigation for gastrointestinal symptoms could reduce the proportion of people diagnosed later for female breast, lung and colorectal, but not prostate cancer. Differences between the four main cancers suggest different policies may be required for individual cancers to improve outcomes. PMID- 26141459 TI - New Cases of DHTKD1 Mutations in Patients with 2-Ketoadipic Aciduria. AB - 2-Ketoadipic aciduria (OMIM 204750), a defect in the catabolic pathway of tryptophan, lysine, and hydroxylysine, is characterized by elevations in 2 ketoadipic, 2-aminoadipic, and 2-hydroxyadipic acids. Patients with the aforementioned biochemical profile have been described with a wide range of clinical presentations, from early-onset developmental delay, epilepsy, ataxia, and microcephaly to completely normal. This broad range of phenotypes has led some to question whether 2-ketoadipic aciduria represents a true disease state or if the biochemical abnormalities found in these patients merely reflect an ascertainment bias. We present four additional individuals from two families, with 2-ketoadipic aciduria with compound heterozygous or homozygous mutations in DHTKD1, three of which remain asymptomatic. PMID- 26141460 TI - Pitfalls in Diagnosing Neuraminidase Deficiency: Psychosomatics and Normal Sialic Acid Excretion. AB - Neuraminidase deficiency (mucolipidosis I, sialidosis types I and II, cherry-red spot myoclonus syndrome) is a lysosomal storage disorder with an expanding clinical phenotype. Here, we report the striking diagnostic history of late-onset neuraminidase deficiency in two sisters, currently aged 14 (patient 1) and 15 (patient 2).Patient 1 was referred for evaluation of her vision after a traffic accident. During this examination, nummular cataract, macular cherry-red spot, and optic nerve atrophy were seen. Furthermore, tremors were noticed in her arms and legs. This combination suggested a lysosomal storage disorder. Her family history revealed an older sister, patient 2, who had a long history of unexplained neurologic symptoms; she was under unsuccessful treatment for conversion disorder. Patient 2 showed identical ophthalmological findings. In retrospect, she had presented with avascular osteonecrosis of the right femur head at age 9.Urinary oligosaccharide patterns and enzyme activity revealed neuraminidase deficiency in both patients. Urinary-bound sialic acid levels were normal. Sequencing of NEU1 demonstrated two known compound heterozygous mutations (c.1195_1200dup p.His399_Tyr400dup; c.679G>A, p.Glu227Arg).The substantial time window between onset of typical symptoms and diagnosis in patient 2 suggests inadequate awareness of lysosomal storage disorders among clinicians. Of special interest is the observation that normal urinary sialic acid levels do not exclude neuraminidase deficiency. Urinary oligosaccharide screening is essential to diagnosis in such cases. In addition, patient 2 is the fourth case in the literature with a history of femur head necrosis. Bone defects might therefore be an early manifestation of late-onset neuraminidase deficiency. PMID- 26141461 TI - Attitudes and perceived risk of cannabis use in Irish adolescents. AB - INTRODUCTION: Cannabis is the most widely used illicit drug in the developed world and its use is associated with several adverse physical and mental health effects and negative social outcomes. Earlier use of cannabis increases the risk of adverse effects. Attitudes and perceived risk towards drugs are regarded as strong influences in determining whether or not a person uses cannabis, but there is little existing research on Irish teenagers' attitudes to the risks of this drug. METHODS: This was a descriptive, cross-sectional study using a structured, anonymous questionnaire. The study was undertaken in nine public and private secondary schools in Cork City and suburbs. Students aged 15-18 and in fourth, fifth or sixth year of school were included. RESULTS: Of the 507 participating students, 39.3 % (n = 199) reported previous cannabis use. There were significantly lower levels of perceived risk of cannabis among those who had used the drug compared with those who had not, for all categories of risk (p < 0.01). Attitudes towards cannabis were more liberal among males and those with previous use of the drug. A minority of students (n = 92; 18.2 %) support legalisation of cannabis. The majority of teenagers (n = 382; 75.8 %) believe that they are not given enough information about the drug. CONCLUSIONS: Cannabis use is very widespread among teenagers in Cork. There are relatively low levels of perceived risk of mental and physical health problems with use of the drug. Attitudes towards cannabis are associated with personal use of the drug and gender. PMID- 26141462 TI - Administration of hydrogen sulfide protects ischemia reperfusion-induced acute kidney injury by reducing the oxidative stress. AB - BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulfide (H2S) has been known as a novel gaseous signaling molecule. AIMS: The aim of this study was to investigate whether the efficacy of H2S in protecting against renal IRI is through its antioxidative effect. METHOD: In this study, rats were randomized into Sham, IR, or sodium hydrosulfide (NaHS, an H2S donor) groups. To establish a model of renal IRI, both renal arteries were occluded for 55 min and then declamped to allow reperfusion for 24 h. Rats in the NaHS group received intraperitoneal injections of 75 MUmol/kg NaHS 10 min before the onset of ischemia and immediately after the onset of reperfusion. Sham group underwent laparotomy without cross-clamping of renal pedicles. After reperfusion, plasma and renal tissue samples were collected for functional, histological, and oxidative stress evaluation. RESULTS: The IR group exhibited significant rise in plasma creatinine, blood urea nitrogen (BUN), renal malondialdehyde (MDA) concentration, and significant reduction of renal superoxide dismutase (SOD) activity. Treatment with NaHS reduced the levels of plasma creatinine, BUN, renal MDA concentration, and increased SOD activity in the kidneys. NaHS improved renal histological changes in comparison to IR group. CONCLUSION: Our data demonstrated that H2S can protect against renal IRI and that its therapeutic effects may be mediated by reducing oxidative stress. PMID- 26141463 TI - Intraoperative Adverse Events: Risk Adjustment for Procedure Complexity and Presence of Adhesions Is Crucial. AB - BACKGROUND: Benchmarking the quality of intraoperative care by comparing the rates of intraoperative adverse events (iAEs) necessitates adequate risk adjustment. We sought to identify the patient- and procedure-related risk factors for iAEs. STUDY DESIGN: Our 2007 to 2012 institutional American College of Surgeons NSQIP and administrative databases were linked and then screened for iAEs using the Patient Safety Indicator "Accidental Puncture/Laceration." Intraoperative adverse events were confirmed by systematic review of medical records. Comorbidities were assessed using American College of Surgeons NSQIP variables. Adhesiolysis was determined using CPT codes for lysis of adhesions. Operative complexity was determined using relative value units. Multivariable models were constructed to identify independent predictors of iAEs. Sensitivity analyses were performed in uniform samples of operations. RESULTS: Of 9,292 patients, 218 iAEs were confirmed in 183 patients. Median patient age was 56 years old and 54% were female. Compared with patients without iAEs, iAE patients were older (median 61 vs 56 years; p < 0.001), more functionally dependent (9% vs 5%; p = 0.028), and had higher American Society of Anesthesiologists class (>=3 in 45% vs 35%; p = 0.004); their procedures were more complex (median relative value units 29 vs 23; p < 0.001), more likely open (48% vs 21%; p < 0.001), and more often required adhesiolysis (44% vs 18%; p < 0.001). In multivariable analyses, adhesiolysis (odds ratio = 2.34; 95% CI, 1.71-3.21; p < 0.001), higher operative complexity (third vs first relative value units quartile: odds ratio = 3.36; 95% CI, 1.66-6.78; p < 0.001; fourth vs first quartile: odds ratio = 5.97; 95% CI, 3.01-11.86; p < 0.001), and open surgical approach (odds ratio = 2.04; 95% CI, 1.39-3.01; p < 0.001) independently predicted iAEs. Sensitivity analyses confirmed adhesiolysis and higher operative complexity as independent iAE predictors. CONCLUSIONS: Adhesiolysis and higher operative complexity predict an increased risk for iAE. Attempts to benchmark the quality of intraoperative care need to adequately risk adjust for these factors. PMID- 26141464 TI - Preoperative vs Postoperative Eradication of Helicobacter pylori in 150 Patients with Gastric Cancer: A Randomized Controlled Trial. AB - BACKGROUND: The Maastricht, Asia-Pacific consensus guidelines strongly recommend eradication of Helicobacter pylori in patients who have a history of gastric cancer. This open-label, single-center, randomized controlled trial was conducted to investigate the appropriate timing of eradication for patients undergoing gastrectomy. STUDY DESIGN: One hundred and fifty patients scheduled to undergo gastrectomy were allocated to either a preoperative or a postoperative group. The eradication regimen was a common triple therapy: rabeprazole, amoxicillin, and clarithromycin [corrected]. Patients in the preoperative group were treated with the regimen, followed by surgery, and patients in the postoperative group were treated after postoperative day 8. The primary end point was the proportion of patients achieving successful eradication in the remnant stomach. The definition of successful eradication was negativity in both the C13 urea breath test and for the antigen in feces at 6 months after surgery. RESULTS: Eight patients were excluded, and the remaining one hundred and forty-two, 70 in the preoperative group and 72 in the postoperative group, were included on an intention to treat basis. The procedures used were gastrectomy with Billroth I, Roux-en-Y, and pylorus-preserving gastrectomy in 18, 70, and 57 patients, respectively. The proportion of patients showing successful eradication hardly differed between the 2 groups, 68.6% vs 69.4% (p = 1.000) in the pre- and postoperative groups, respectively. Subgroup analysis also demonstrated no significant difference among the reconstruction methods used. CONCLUSIONS: Preoperative H pylori eradication therapy for gastric cancer patients scheduled for gastrectomy is not necessary, regardless of the planned reconstruction procedure. PMID- 26141465 TI - External Validation of a Score Predictive of Recurrence after Radical Surgery for Non-Cardia Gastric Cancer: Results of a Follow-Up Study. AB - BACKGROUND: A score predictive of tumor recurrence after radical surgery for non cardia gastric cancer was previously developed in Italian centers. The aim of this study was to validate the score in a consecutive cohort with prospectively collected follow-up data. STUDY DESIGN: Of 1,178 patients surgically treated between 1998 and 2006, six hundred and thirty-five patients who fulfilled the selection criteria and completed the follow-up program were available for analysis. The score value for each patient was calculated using the formula obtained from a logistic regression model. Discrimination and calibration of the score in the validation group were evaluated and compared with the data of 438 patients in the study group where the score was developed. RESULTS: Most patients in both groups had very low or very high score values. In the validation group, the observed recurrence rates ranged from 5% to 92% in different score strata. The area under the receiver operating characteristic curve was 0.889 (95% CI, 0.864-0.914; p < 0.001), indicating a high discrimination value of the score for recurrence. A good calibration was observed by comparing the predicted risk with the actual risk of recurrence. With a score cut-off value of 50, sensitivity, specificity, and overall accuracy were 74%, 86%, and 81%, respectively. An inverse correlation between the time to recurrence and score level was also estimated (R(2) = 0.119; p < 0.001). CONCLUSIONS: The high predictive value of the score was validated in a consecutive cohort. These results might allow the introduction of the score in clinical practice for Western patients. PMID- 26141466 TI - Effect of Daikenchuto, a Traditional Japanese Herbal Medicine, after Total Gastrectomy for Gastric Cancer: A Multicenter, Randomized, Double-Blind, Placebo Controlled, Phase II Trial. AB - BACKGROUND: Daikenchuto (DKT) has widely been used to improve abdominal symptoms by being expected to accelerate bowel motility. The purpose of this study is to examine the efficacy and safety of DKT for prevention of ileus and associated gastrointestinal symptoms after total gastrectomy. STUDY DESIGN: Two hundred and forty-five gastric cancer patients who underwent total gastrectomy were enrolled. Patients received either DKT (15.0 g/d) or matching placebo from postoperative days 1 to 12. Primary end points were time to first flatus, time to first bowel movement (BM), and frequency of BM. Secondary end points included quality of life, C-reactive protein level, symptoms indicative of a severe gastrointestinal disorder, and incidence of postoperative ileus. RESULTS: A total of 195 patients (DKT, n = 96; placebo, n = 99) were included in the per-protocol set analysis. There were no significant differences between the groups in terms of patient background characteristics. Median time to first BM was shorter in the DKT group than in the placebo group (94.7 hours vs 113.9 hours; p = 0.051). In patients with high medication adherence, median time to first BM was significantly shorter in the DKT group than in the placebo group (93.8 hours vs 115.1 hours; p = 0.014). Significantly fewer patients in the DKT group had >=2 symptoms of gastrointestinal dysfunction than those in the placebo group on postoperative day 12 (p = 0.026). CONCLUSIONS: Administration of DKT during the immediate postoperative period after total gastrectomy appears to promote early recovery of postoperative bowel function. PMID- 26141467 TI - Saline vs Tissue Plasminogen Activator Irrigations after Drain Placement for Appendicitis-Associated Abscess: A Prospective Randomized Trial. AB - BACKGROUND: Emerging data suggest instillation of tissue plasminogen activator (tPA) is safe and potentially efficacious in the treatment of intra-abdominal abscess. To date, prospective comparative data are lacking in children. Therefore, we conducted a randomized trial comparing abscess irrigation with tPA and irrigation with saline alone. STUDY DESIGN: After IRB approval, children with an abscess secondary to perforated appendicitis who had a percutaneous drain placed for treatment were randomized to twice-daily instillation of 13 mL 10% tPA or 13 mL normal saline. All patients were treated with once-daily dosing of ceftriaxone and metronidazole throughout their course. The primary end point variable was duration of hospitalization after drain placement. Using a power of 0.8 and an alpha of 0.05, a sample size of 62 patients was calculated. RESULTS: Sixty-two patients were enrolled between January 2009 and February 2013. There were no differences in demographics, abscess size, abscess number, admission WBC, or duration of symptoms. Duration of hospitalization after drainage was considerably longer with the use of tPA. There was no difference in total duration of hospitalization, days of drainage, or days of antibiotics. However, medication charges were higher with tPA. CONCLUSIONS: There are no advantages to routine tPA flushes in the treatment of abdominal abscess secondary to perforated appendicitis in children. PMID- 26141468 TI - Racial and Regional Disparities in the Effect of the Affordable Care Act's Dependent Coverage Provision on Young Adult Trauma Patients. AB - BACKGROUND: Disparities in trauma outcomes based on insurance and race are especially pronounced among young adults who have relatively high uninsured rates and incur a disproportionate share of trauma in the population. The 2010 Dependent Coverage Provision (DCP) of the Affordable Care Act (ACA) allowed young adults to remain on their parent's health insurance plans until age 26 years, leading to >3 million young adults gaining insurance. We investigated the impact of the DCP on racial disparities in coverage expansion among trauma patients. STUDY DESIGN: Using the 2007-2012 National Trauma Data Bank, we compared changes in coverage among 529,844 19- to 25-year-olds with 484,974 controls aged 27 to 34 years not affected by the DCP. Subgroup analyses were conducted by race and ethnicity and by census region. RESULTS: The pre-DCP uninsured rates among young adults were highest among black patients (48.1%) and Hispanic patients (44.3%), and significantly lower among non-Hispanic white patients (28.9%). However, non Hispanic white young adults experienced a significantly greater absolute reduction in the uninsured rate (-4.9 percentage points) than black (-2.9; p = 0.01) and Hispanic (-1.7; p < 0.001) young adults. These absolute reductions correspond to a 17.0% relative reduction in the uninsured rate for white patients, 6.1% for black patients, and 3.7% for Hispanic patients. Racial disparities in the provision's impact on coverage among trauma patients were largest in the South and West census regions (p < 0.01). CONCLUSIONS: Although the DCP increased insurance coverage for young adult trauma patients of all races, both absolute and relative racial disparities in insurance coverage widened. The extent of these racial disparities also differed by geographic region. Although this policy produced overall progress toward greater coverage among young adults, its heterogeneous impact by race has important implications for future disparities research in trauma. PMID- 26141469 TI - Using Merged Clinical and Claims Registry Data to Identify High Utilizers of Surgical Inpatient Care 1 Year after Colectomy. AB - BACKGROUND: Under bundled payment initiatives, providers will be held financially responsible for patients' acute and post-acute care costs. Certain patients, termed high utilizers, use disproportionate shares of resources during 1 year. The aim of this study was to identify high utilizers, describe their costs, and determine whether preoperative characteristics predict high utilizer status. STUDY DESIGN: Colectomy patients with 1-year follow-up were identified in a linked clinical (American College of Surgeons NSQIP) and administrative (Medicare inpatient claims) dataset (2005 to 2008). Cost of inpatient care was calculated by multiplying patient Medicare charges in each cost center by cost-to-charge ratios from the Medicare cost reports. A mixed-effects logistic model quantified the association between preoperative characteristics and being a high utilizer after elective and emergent colectomies. RESULTS: One thousand and fifty-five of 10,561 colectomy patients accounted for >50% of the inpatient care cost of the entire cohort during 1 year postoperatively. This top decile of patients were labeled high utilizers and had substantially greater costs in the following cost centers: intensive care ($36,322 vs $0), respiratory ($2,875 vs $22), radiology ($649 vs $29), and cardiology ($5,057 vs $166) (all p < 0.001). High utilizers more frequently had emergent index colectomies (43% vs 17%; p < 0.001). Patients with American Society of Anesthesiologists class IV and V had 2-fold increased odds of being high utilizers after both elective (odds ratio = 2.72; 95% CI, 1.89 3.90) and emergent colectomies (odds ratio = 2.09; 95% CI, 1.23-3.55). CONCLUSIONS: Patients in the top cost decile account for the majority of costs in the year after colectomy, disproportionately accumulate those costs in particular cost centers, and can be identified preoperatively. PMID- 26141470 TI - Angiotensin Inhibition Is Associated with Preservation of T-Cell and Monocyte Function and Decreases Multiple Organ Failure in Obese Trauma Patients. AB - BACKGROUND: Obese patients are more prone to post-injury multiple organ failure (MOF). Obesity pathophysiology includes an adipose-tissue-derived, renin angiotensin-aldosterone system affecting inflammatory responses via leukocyte angiotensin receptors. We hypothesized that obese patients receiving pre-injury angiotensin-converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB) therapy would have decreased MOF and differences in immune cell frequencies. STUDY DESIGN: We analyzed the Inflammation and the Host Response to Injury trauma-related database. Patients receiving pre-injury ACE or ARB were stratified as obese (BMI >30 kg/m(2)) or nonobese (BMI <30 kg/m(2)). Groups were age, sex, and Injury Severity Score matched against patients not receiving this therapy. Primary end points were Marshall Multiple Organ Dysfunction Score, Denver-2 Postinjury MOF Score, leukocyte markers on T cells, and monocytes measured by flow cytometry. RESULTS: We evaluated 1,932 patients. One hundred and ten were receiving pre-injury ACE/ARB; 94 patients had data available to calculate BMI. Obese patients receiving ACE/ARB showed maximum Marshall (5.83 +/- 2.87) and Denver-2 (2.45 +/- 2.32) scores similar to nonobese patients receiving or not receiving ACE/ARB, and obese patients not receiving ACE/ARB had significantly higher Marshall (6.49 +/- 2.57; p = 0.009) and Denver-2 (3.33 +/- 2.21; p = 0.006) scores. Leukocyte analysis suggested improved T-cell function and monocyte maturation in obese patients on ACE/ARB. CONCLUSIONS: Obese patients receiving preinjury ACE/ARB therapy demonstrate post-injury MOF scores similar to nonobese patients; obese patients not receiving these medications have greater post-injury MOF. Leukocyte analysis demonstrates improved immune regulation. Modulation of the renin-angiotensin-aldosterone system pathway might represent a novel therapeutic target in severely injured obese patients. PMID- 26141471 TI - Number of Renal Columns Invaded by Tumor: A Novel Parameter for Predicting Complexity and Outcomes of Off-Clamp Open Partial Nephrectomy. AB - BACKGROUND: The number of renal columns invaded by tumor (NRC) can determine the tumor complexity and perioperative outcomes of off-clamp open partial nephrectomy (OPN). We aimed to propose a novel and simple scoring system and examine the relationship between NRC and perioperative outcomes after off-clamp OPN. STUDY DESIGN: We retrospectively evaluated 202 patients with contrast-enhanced CT imaging who underwent off-clamp OPN between January 2008 and November 2014. The number of renal columns invaded by tumor was correlated to baseline demographics and perioperative outcomes as a categorical variable using multivariable logistic regression analysis. RESULTS: The mean tumor size was 2.5 cm (+/-1.3 cm). The number of renal columns invaded by tumor had the highest correlation coefficients with estimated blood loss (coefficient = 0.485; p < 0.001), operative time (coefficient = 0.310; p < 0.001), postoperative drainage (coefficient = 0.307; p < 0.001), and hospital length of stay (coefficient = 0.144; p = 0.041). Multivariable logistic regression demonstrated NRC to be an independent predictor of estimated blood loss >=500 mL, postoperative renal function, operative time, and surgical complications. This predictive ability of NRC was superior to the R.E.N.A.L. (radius exophyic/endophytic nearness anterior/posterior location) score and PADUA (preoperative aspects and dimensions used for an anatomical) score. Spearman correlation coefficient of NRC calculations between the 2 observers was 0.941 (p < 0.001). CONCLUSIONS: The number of renal columns invaded by tumor is a novel, intuitive, and practical parameter that could be used to quantify renal tumor complexity and predict the risk of perioperative outcomes after off-clamp OPN. Specifically, NRC correlates with estimated blood loss, operative time, surgical complications, renal function, and conversion to on clamp. In the future, NRC can be integrated with other parameters, such as tumor location, to assemble a new scoring system. PMID- 26141472 TI - Threat to Parental Role: A Possible Mechanism of Altered Self-Concept Related to Carrier Knowledge. AB - Researchers and clinicians have suggested that learning one is a carrier for a genetic disorder has the potential to alter self-concept. Concerns about self concept have influenced the development of policies regarding the availability of carrier testing for minors and the informed-consent process. A literature review identified three mechanisms through which self-concept has been proposed to be affected: altered perception of genetic identity, diminished social identity, and an altered perception of health. This paper presents a conceptual framework developed from identity theory and the "self's response to threat" to propose a fourth mechanism: threat to the parental role. Clarification of the role of self concept, the threat to self-concept related to carrier knowledge, and coping behaviors activated in response to this threat would help to target appropriate genetic counseling interventions. PMID- 26141473 TI - Genetic Counseling for Fragile X Syndrome: Recommendations of the National Society of Genetic Counselors. AB - The National Society of Genetic Counselors' (NSGC) recommendations for fragile X syndrome (FXS) genetic counseling are intended to assist health care professionals who provide genetic counseling for individuals and families in whom the diagnosis of FXS is strongly suspected or has been made. The recommendations are the opinions of genetic counselors with expertise in FXS counseling and are based on clinical experience, a review of pertinent English language medical articles, and reports of expert committees. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a particular client. PMID- 26141475 TI - Commentary: A Patient's Perspective on Predictive Testing for Alzheimer Disease. PMID- 26141474 TI - Presymptomatic Genetic Testing with an APP Mutation in Early-Onset Alzheimer Disease: A Descriptive Study of Sibship Dynamics. AB - Early-onset Alzheimer disease (AD) accounts for only 5% of all cases of Alzheimer disease. To date, mutations in three different genes, the Amyloid precursor protein (APP), Presenilin 1 (PS1), and Presenilin 2 (PS2), have been identified as causative in early-onset AD, making predictive testing possible. Predictive testing for early-onset Alzheimer disease is a relatively new phenomenon. This paper describes the process of identifying a new mutation in the APP gene associated with early-onset AD, notifying family members, and offering participation in research as well as predictive testing. The goal is to share the complexities of predictive testing in a sibship newly identified as being at risk for an adult-onset, incurable neurodegenerative disease. PMID- 26141476 TI - Update and Review: Supernumerary Marker Chromosomes. AB - Supernumerary marker chromosomes (SMCs) are found in individuals with normal and abnormal clinical phenotypes. Correlations between karyotype and phenotype have been made in only a few circumstances. This article summarizes the most recent information regarding supernumerary marker chromosomes, including genetic counseling issues. PMID- 26141477 TI - Commentary: Computers and Genetic Counseling-Time for a Dialogue? PMID- 26141478 TI - Genetic Library. PMID- 26141479 TI - Early Effects of Single and Low-Frequency Repeated Administration of Teriparatide, hPTH(1-34), on Bone Formation and Resorption in Ovariectomized Rats. AB - Intermittent repeated administration of teriparatide (TPTD) has potent anabolic effects on bones in vivo. However, TPTD has both anabolic and catabolic effects on osteoblasts in vitro, and the mechanisms underlying its promotion of bone formation are unclear. This study aimed to elucidate the time-dependent changes in bone formation and resorption by examining changes in bone turnover markers and bone tissue over time after TPTD administration with low frequency in ovariectomized rats. The amount of serum osteocalcin, a bone formation marker, was transiently reduced after single TPTD administration, but increased thereafter, remaining increased for several days. In contrast, the amount of excreted urinary C-telopeptide, a bone resorption marker, increased transiently after single TPTD administration, and subsequently returned to control levels on the day after administration. Tissue histomorphometric analyses conducted 8 h after administration showed no changes in bone formation or bone resorption parameters. However, at 48 h, the bone formation parameters OS/BS and Ob.S/BS were increased, while the bone resorption parameter ES/BS was decreased. After repeated TPTD administration for 4 weeks, OS/BS, Ob.S/BS, and MS/BS increased, while Oc.S/BS decreased. Serum osteocalcin at 4 weeks after repeated administration was significantly correlated with OS/BS and Ob.S/BS. These present findings indicate that TPTD has dual, time-dependent effects on bone resorption and bone formation. Immediately after single administration, there was transient promotion of bone resorption and suppression of bone formation. However, sustained stimulation of bone formation occurred thereafter. Furthermore, these data suggest that this sustained bone formation led to anabolic effects with repeated TPTD administration. PMID- 26141480 TI - Effects of Domperidone on QT Interval in Children with Gastroesophageal Reflux Disease. AB - BACKGROUND: Domperidone has been widely used in children with gastroesophageal reflux disease (GERD). Studies on the effects of domperidone on corrected QT interval (QTc) in young children are limited. Our aim was to study the effect of domperidone on the repolarization abnormalities assessed by electrocardiogram (ECG) in young children. METHODS: ECG was performed in children <2 years of age before and after taking domperidone orally 0.3 mg/kg three times/day for at least a 1 week period. Each ECG was reviewed and QT, RR, and Tpeak to Tend intervals (TpTe) were measured to calculate the QTc and TpTe/QT ratio. RESULTS: A total of 22 patients (12 male) with a median age of 8.5 months (1-24 months) were enrolled. Most patients (59.1%) were under 1 year of age. The median baseline QTc (410 milliseconds, 350-450 milliseconds) was not significantly different from the QTc after taking domperidone (410 milliseconds, 320-560 milliseconds), p = 0.159. Only two patients showed a QTc increase >=450 milliseconds. The baseline TpTe interval and TpTe/QT (105 milliseconds, 60-170 milliseconds and 0.27 milliseconds, 0.15-0.43 milliseconds) were significantly greater than the TpTe interval and TpTe/QT in children after taking domperidone (90 milliseconds, 60 140 milliseconds and 0.22 milliseconds, 0.15-0.29 milliseconds), p = 0.001 and 0.004, respectively. CONCLUSIONS: Our data demonstrate that domperidone treatment over a short-term period in children <2 years of age did not lengthen QTc significantly; however, QTc increased >=450 milliseconds in two patients with concomitant lansoprazole. Routine baseline and follow-up ECG may not be necessary in each individual case receiving only domperidone. PMID- 26141481 TI - Takayasu's Arteritis Presenting as Monocular Visual Loss. PMID- 26141482 TI - Neurodevelopmental Outcomes in Very Low Birth Weight Infants Using Aminophylline for the Treatment of Apnea. AB - BACKGROUND: Aminophylline has been widely used in the treatment of apneic episodes in premature infants. Animal models suggest caution in the use of aminophylline as it may increase the cerebral metabolic rate and decrease the rate of anoxic survival in neonates. This study aimed to evaluate the neurological outcomes in very low birth weight (VLBW) infants treated with aminophylline for apnea in our neonatal intensive care unit. METHODS: All VLBW infants (body birth weight < 1500 g) admitted to our neonatal intensive care unit between January 2000 and December 2011 were enrolled in this retrospective study. Clinical characteristics and outcomes of these infants were reviewed and recorded. Scores on the Bayley Scales of Infant Development at 6 months, 12 months, and 18 months of corrected age were also recorded. The controls (who did not receive aminophylline) were matched for gestational age with the aminophylline group. RESULTS: The baseline characteristics of the aminophylline group and the control group were similar. The neurodevelopmental outcomes as well as rates of patent ductus arteriosus, brain injury, severe retinopathy of prematurity, and necrotizing enterocolitis were not significantly different between the two groups. Only bronchopulmonary dysplasia remained significantly higher in the aminophylline group after adjusting for risk factors (48.08% vs. 21.15%; adjusted odds ratio: 12.50; p < 0.001). CONCLUSION: Aminophylline therapy for apnea of prematurity had no apparent and additional risk on the neurodevelopmental outcomes of VLBW infants at a corrected age of 18 months. Further studies with a larger sample size are needed to confirm the adverse neurological effects of aminophylline treatment. PMID- 26141483 TI - Serum Lactate, Brain Magnetic Resonance Imaging and Outcome of Neonatal Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia. AB - BACKGROUND: Serum lactate was used to predict the severity and outcome of neonatal hypoxic ischemic encephalopathy (HIE) before the era of therapeutic hypothermia (TH). There is no report on neurodevelopment (ND) outcome of neonates with HIE treated with TH in Taiwan. METHODS: Between April 2011 and December 2012, newborn infants admitted to Chang Gung Memorial Hospital (CGMH), with gestational age > 35 weeks and birth weight >= 1800 g, who had acute perinatal events, evidence of significant fetal compromise, and ongoing clinical encephalopathy were prospectively enrolled for TH. Whole body cooling method was used to maintain the affected neonate's esophageal temperature at 33.5 +/- 0.5 degrees C for 72 hours. Demographic data were recorded and hemogram, biochemical parameters, serum lactate, and creatine kinase (CK) were measured as well. Brain magnetic resonance imaging (MRI) was performed between 7 and 14 days of life. ND outcome of infants was evaluated by Bayley Scales of Infant Development, third edition (BSID-III) at 24 months of corrected age. Poor ND (PND) outcome was defined as infants surviving with either disability or ND delay. RESULTS: Seventeen patients were enrolled. Fifty-nine percent of babies (10/17) were born through cesarean section and 77% of babies (13/17) were transferred from outside hospitals. Six babies were moderate HIE and 11 babies were severe HIE. Among the 14 surviving patients, eight infants had PND outcome. There was no difference in demographic data between infants with and without PND. Serum level of lactate (mg/dL) after 72 hours of TH was higher (35.6 vs. 13.8, p = 0.042) in infants with PND. Neonates with abnormal brain MRI findings were also associated with PND (p = 0.01). CONCLUSION: This is the first report on ND outcome of neonates with HIE treated with TH in Taiwan. Higher serum level of lactate following TH and abnormal results of brain MRI are associated with poor ND outcome. PMID- 26141484 TI - Evaluation of a novel canine activity monitor for at-home physical activity analysis. AB - BACKGROUND: Accelerometers are motion-sensing devices that have been used to assess physical activity in dogs. However, the lack of a user-friendly, inexpensive accelerometer has hindered the widespread use of this objective outcome measure in veterinary research. Recently, a smartphone-based, affordable activity monitor (Whistle) has become available for measurement of at-home physical activity in dogs. The aim of this research was to evaluate this novel accelerometer. Eleven large breed, privately owned dogs wore a collar fitted with both the Whistle device and a previously validated accelerometer-based activity monitor (Actical) for a 24-h time period. Owners were asked to have their dogs resume normal daily activities. Total activity time obtained from the Whistle device in minutes was compared to the total activity count from the Actical device. Activity intensity from the Whistle device was calculated manually from screenshots of the activity bars displayed in the smartphone-application and compared to the activity count recorded by the Actical in the same 3-min time period. RESULTS: A total of 3740 time points were compared. There was a strong correlation between activity intensity of both devices for individual time points (Pearson's correlation coefficient 0.81, p < 0.0001). An even stronger correlation was observed between the total activity data between the two devices (Pearson's correlation coefficient 0.925, p < 0.0001). CONCLUSIONS: Activity data provided by the Whistle activity monitor may be used as an objective outcome measurement in dogs. The total activity time provided by the Whistle application offers an inexpensive method for obtaining at-home, canine, real-time physical activity data. Limitations of the Whistle device include the limited battery life, the need for manual derivation of activity intensity data and data transfer, and the requirement of Wi-Fi and Bluetooth availability for data transmission. PMID- 26141486 TI - Imaging features of systemic cystic angiomatosis. PMID- 26141485 TI - Subarachnoid hemorrhage in ten questions. AB - Traumatic subarachnoid hemorrhage (SAH) has an annual incidence of 9 per 100 000 people. It is a rare but serious event, with an estimated mortality rate of 40% within the first 48hours. In 85% of cases, it is due to rupture of an intracranial aneurysm. In the early phase, during the first 24hours, cerebral CT, combined with intracranial CT angiography is recommended to make a positive diagnosis of SAH, to identify the cause and to investigate for an intracranial aneurysm. Cerebral MRI may be proposed if the patient's clinical condition allows it. FLAIR imaging is more sensitive than CT to demonstrate a subarachnoid hemorrhage and offers greater degrees of sensitivity for the diagnosis of restricted subarachnoid hemorrhage in cortical sulcus. A lumbar puncture should be performed if these investigations are normal while clinical suspicion is high. PMID- 26141487 TI - Severe hemoptysis: From diagnosis to embolization. AB - Severe hemoptysis is life-threatening to patients because of the asphyxia it causes. The diagnosis and treatment are therefore urgent and chest imaging is essential. Multidetector CT-angiography provides an exhaustive non-invasive assessment which includes localization, mechanisms, causes and severity of the hemoptysis. It is an invaluable step in preparation for endovascular treatment which is the first line invasive therapy, particularly with bronchial arteriography embolization in the majority of cases (over 90%) and erosion or rupture of the pulmonary artery in less than 10% of cases. Hemoptysis control is achieved in 65 to 92% of cases depending on the cause. PMID- 26141489 TI - Panning for sperm gold: Isolation and purification of apyrene and eupyrene sperm from lepidopterans. AB - We describe a simple and straightforward procedure for the purification and separation of apyrene and eupyrene forms of lepidopteran sperm. The procedure is generally applicable to both butterfly and moth species with results varying according to the relative amounts of sperm produced and size of sperm storage organs. The technique relies upon inherent differences between eupyene sperm bundles and free apyrene sperm morphology. These differences allow for separation of the sperm morphs by repeated "panning" of sperm bundles into the center of a plastic dish. The purified eupyrene sperm bundles can then be removed and apyrene sperm collected from the supernatant by centrifugation. Efficacy of the purification process was confirmed by light microscopy and gel electrophoresis of the resulting fractions. Both one- and two-dimensional gel electrophoresis identified significant protein differences between the fractions further suggesting that the panning procedure effectively separated eurpyrene from apyrene sperm. The panning procedure should provide a convenient and accessible technique for further studies of sperm biology in lepidopterans. PMID- 26141488 TI - Ikaros could be a key factor in the maintenance of "B-side" of B-1 cells. AB - Ikaros, a zinc finger transcription factor, is an important regulator of the hematopoietic system. Several studies have suggested the role of Ikaros in the development, maturation, activation and differentiation of lymphocytes. To elucidate this mechanism, it is important to understand how this transcription factor works in the dichotomy of the hematopoietic system, a topic that remains uncertain. Herein, we investigated the role of Ikaros in the control of the lymphomyeloid phenotype of B-1 lymphocytes. We found that Ikaros, as well as its target genes, are expressed in B-1 cells,. Moreover, Ikaros positively regulates the expression of Flt3, Gfi and Il7r, while it down-regulates PU.1. During the induction of differentiation of B-1 cells toward phagocytes, Ikaros transcription was reduced. Taken together, these data pointed to the relevance of Ikaros in the maintenance of the promiscuous gene profile of B-1 cells. It could be suggested that Ikaros functions as a guardian of B-1 lymphoid pattern, and that its absence directs the differentiation of B-1 cells into phagocytes. PMID- 26141490 TI - Government abolishes child poverty target. PMID- 26141492 TI - CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease. AB - Abnormalities in neuronal cholesterol homeostasis have been suspected or observed in several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, it has not been demonstrated whether an increased abundance of cholesterol in neurons in vivo contributes to neurodegeneration. To address this issue, we used RNA interference methodology to inhibit the expression of cholesterol 24-hydroxylase, encoded by the Cyp46a1 gene, in the hippocampus of normal mice. Cholesterol 24-hydroxylase controls cholesterol efflux from the brain and thereby plays a major role in regulating brain cholesterol homeostasis. We used an adeno-associated virus vector encoding short hairpin RNA directed against the mouse Cyp46a1 mRNA to decrease the expression of the Cyp46a1 gene in hippocampal neurons of normal mice. This increased the cholesterol concentration in neurons, followed by cognitive deficits and hippocampal atrophy due to apoptotic neuronal death. Prior to neuronal death, the recruitment of the amyloid protein precursor to lipid rafts was enhanced leading to the production of beta-C-terminal fragment and amyloid beta peptides. Abnormal phosphorylation of tau and endoplasmic reticulum stress were also observed. In the APP23 mouse model of Alzheimer's disease, the abundance of amyloid-beta peptides increased following inhibition of Cyp46a1 expression, and neuronal death was more widespread than in normal mice. Altogether, these results suggest that increased amounts of neuronal cholesterol within the brain may contribute to inducing and/or aggravating Alzheimer's disease. PMID- 26141493 TI - Development of a novel chromogenic method, Penta-well test, for rapid prediction of beta-lactamase classes produced in clinical Enterobacteriaceae isolates. AB - We developed a novel chromogenic method, Penta-well test, which enables the rapid detection and classification of beta-lactamases in clinical Enterobacteriaceae isolates. This test is based on a combination of nitrocefin and 3 beta-lactamase inhibitors specific to classes A, B, and/or C, with nitrocefin hydrolysis by beta lactamases being assessed by optical density measurements at 490 nm. When the cutoff value for each beta-lactamase class was determined (0.09, 0.4, and 0.55 for class A, class B, and class C beta-lactamase producers, respectively), the sensitivity and specificity of classification were 93.5% and 68.8% for class A, 93.8% and 100% for class B, and 86.7% and 100% for class C, respectively. Moreover, this method allowed accurate beta-lactamase classification in 20 of 23 (87.0%) isolates producing plural class of beta-lactamases. Thus, the Penta-well test can provide information that would be useful in the accurate detection and classification of beta-lactamases produced by causative bacteria. PMID- 26141494 TI - Integrated nonclinical and clinical risk assessment of the investigational proteasome inhibitor ixazomib on the QTc interval in cancer patients. AB - BACKGROUND: Ixazomib is the first oral, proteasome inhibitor to reach phase III trials. Here, we present an integrated nonclinical and clinical assessment of ixazomib's effect on QTc intervals. METHODS: Nonclinical studies assessed (1) the in vitro binding of ixazomib to the hERG channel and (2) its effect on QT/QTc in dogs (N = 4) via telemetry. Pharmacokinetic-matched triplicate electrocardiograms were collected in four clinical phase I studies of intravenous (0.125-3.11 mg/m(2), N = 125, solid tumors/lymphoma) or oral (0.24-3.95 mg/m(2), N = 120, multiple myeloma) ixazomib. The relationship between ixazomib plasma concentration and heart rate (HR)-corrected QT using Fridericia (QTcF) or population (QTcP) methods was analyzed using linear mixed-effects models with fixed effects for day and time. RESULTS: In vitro binding potency for ixazomib to the hERG channel was weak (K i 24.9 MUM; IC50 59.6 MUM), and nonclinical telemetry studies showed no QT/QTc prolongation at doses up to 4.2 mg/m(2). In cancer patients, ixazomib, when evaluated at doses yielding various plasma concentrations (with 26 % of data greater than mean C max for the 4 mg phase 3 dose), had no meaningful effect on QTc based on model-predicted mean change in QTcF/QTcP from baseline. There was no relationship between ixazomib concentration and RR, suggesting no effect on HR. CONCLUSIONS: Ixazomib has no clinically meaningful effects on QTc or HR. Integrating preclinical data and concentration QTc modeling of phase 1 data may obviate the need for a dedicated QTc study in oncology. A framework for QT assessment in oncology drug development is proposed. PMID- 26141491 TI - The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features. AB - A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE epsilon4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59), and controls (n = 61). Patients with behavioural Alzheimer's disease showed worse memory scores than behavioural variant frontotemporal dementia and did not differ from typical Alzheimer's disease, while executive function composite scores were lower compared to behavioural variant frontotemporal dementia and typical Alzheimer's disease. Voxel-wise contrasts between behavioural and dysexecutive Alzheimer's disease patients and controls revealed marked atrophy in bilateral temporoparietal regions and only limited atrophy in the frontal cortex. In direct comparison with behavioural and those with dysexecutive Alzheimer's disease, patients with behavioural variant frontotemporal dementia showed more frontal atrophy and less posterior involvement, whereas patients with typical Alzheimer's disease were slightly more affected posteriorly and showed less frontal atrophy (P < 0.001 uncorrected). Among 24 autopsied behavioural Alzheimer's disease/dysexecutive Alzheimer's disease patients, only two had primary co-morbid FTD-spectrum pathology (progressive supranuclear palsy). In conclusion, behavioural Alzheimer's disease presentations are characterized by a milder and more restricted behavioural profile than in behavioural variant frontotemporal dementia, co-occurrence of memory dysfunction and high APOE epsilon4 prevalence. Dysexecutive Alzheimer's disease presented as a primarily cognitive phenotype with minimal behavioural abnormalities and intermediate APOE epsilon4 prevalence. Both behavioural Alzheimer's disease and dysexecutive Alzheimer's disease presentations are distinguished by temporoparietal-predominant atrophy. Based on the relative sparing of frontal grey matter, we propose to redefine these clinical syndromes as 'the behavioural/dysexecutive variant of Alzheimer's disease' rather than frontal variant Alzheimer's disease. Further work is needed to determine whether behavioural and dysexecutive-predominant presentations of Alzheimer's disease represent distinct phenotypes or a single continuum. PMID- 26141495 TI - Antibacterial activity of a sterile antimicrobial polyisoprene surgical glove against transient flora following a 2-hours simulated use. AB - BACKGROUND: A surgical glove will protect surgeons and patients only if the glove's integrity remains intact. However, several studies have demonstrated that undetected micro-perforations of surgical gloves are common. Because of the possibility of surgical glove puncture, an antimicrobial surgical glove was developed. The aim of this laboratory based experimental study was to assess the antibacterial efficacy of the interior chlorhexidine-gluconate (CHG)-coat of an antimicrobial synthetic polyisoprene surgical glove by using a standardized microbiological challenge. METHODS: Sixteen healthy adult participants donned one antimicrobial surgical glove and one non-antimicrobial surgical glove randomly allocated to their dominant and non-dominant hand following a crossover design. During a 2-h wear time, participants performed standardized finger and hand movements. Thereafter, the interior surface of excised fingers of the removed gloves was challenged with 8.00 log10 cfu/mL S. aureus (ATCC 6538) or K. pneumoniae (ATCC 4352), respectively. The main outcome measure was the viable mean log10 cfu counts of the two glove groups after 5 min contact with the interior glove's surface. RESULTS: When comparing an antimicrobial glove against an untreated reference glove after 2-h simulated use wear-time, a mean reduction factor of 6.24 log10 (S. aureus) and 6.22 log10 (K. pneumoniae) was achieved after 5 min contact. CONCLUSION: These results demonstrate that wearing antibacterial gloves on hands does not negatively impact their antibacterial activity after 2-h of wear. This may have a potential benefit for patient safety in case of glove puncture during surgical procedures. PMID- 26141496 TI - [Interest of ambulatory simplified acute physiology score (ASAPS) applied to patients admitted in an intensive care unit of an infectious diseases unit in Dakar]. AB - The evaluation of patients by a scale of gravity allows a better categorization of patients admitted in intensive care unit (ICU). Our study had for objective to estimate interest of Ambulatory Simplified Acute Physiologic Score (ASAPS) applied to patients admitted in ICU of infectious diseases department of FANN hospital. It was about a descriptive and analytical retrospective study, made from the data found in patients' files admitted into the USI infectious diseases department of FANN hospital in Dakar, from January 1(st), 2009 till December 31st, 2009.The data of 354 patients' files were analyzed. The sex-ratio was 1.77 with an average age of 37.6 years +/- 19.4 years old [5-94 years]. The majority of the patients were unemployed paid (39.6%). The most frequent failures were the following ones: neurological (80.5%), cardio-respiratory (16.7%). The average duration of stay was 6.2 days +/- 8.2 days going of less than 24 hours to more than 10 weeks. The deaths arose much more at night (53.1%) than in the daytime (46.9%) and the strongest rate of death was recorded in January (61.5%), most low in October (26.7%). The global mortality was 48.3%. The rate of lethality according to the highest main diagnosis was allocated to the AIDS (80.5%). The average ambulatory simplified acute physiology score was 5.3 +/- 3.6 with extremes of 0 and 18. The deaths in our series increased with this index (p = 0.000005). The female patients had a rate of lethality higher than that of the men people, 55.5% against 44.2% (p = 0.03). In spite of a predictive score of a high survival (ASAPS < 8), certain number of patients died (n = 105) that is 61.4% of the deaths. The metabolic disturbances, hyperleukocytosis or leukopenia when realised, the presence of a chronic disease, seemed also to influence this lethality. ASAPS only, although interesting, would not good estimate the gravity of patients, where from the necessity thus of a minimum biological balance sheet. It seems better adapted for patients with a high value (ASAPS>=8). This score when it is low, is not correlated, in our study, at a high survival rate as waited in this population. PMID- 26141497 TI - [Analysis of severe Legionellosis hospitalized in intensive care units in Tunisia]. AB - This study is the first one that describes the situation of Legionnaires' disease (LD) in Tunisia, with its clinical and epidemiological characteristics and investigates the risk factors associated with Legionella infections in our country. We conducted a retrospective multicentric study during 5 years (2008 2012) concerning all confirmed LD cases in Tunisia and we investigated risk factors for infection. The total of confirmed LD cases was 14. Incidence was 0.03. Mean age: 53.1, sex ratio (M/F): 2.6. Summer-autumnal peak was noted. Risk factors for infection were: the great humidity at home (n=4), living in community (n=3) and practice ablutions (before prayer) in public places (n=4). Community acquired legionellosis (n=9) and nosocomial (n=2). Pulmonary symptoms (n=11)+/ gastrointestinal (n=6) and/or neurological signs (n=4). Beta lactams therapy failed (n=11). CXR showed bilateral lesions (n=6). Abnormalities in laboratory values were noted: hyponatremia (n=9), high CPK levels (n=9). Diagnosis was confirmed by positive urinary Legionella antigens test (n=10) and by direct immunofluorescence (n=1). Treatment was based on bitherapy (n=10). Five patients died. The incidence of LD appears lower than other countries. Some risk factors, as ablutions, are different from that reported in Western countries and seem to be specific to our society. Given the seriousness of its consequences, it is strongly recommended to improve the national surveillance system up and register LD as notifiable disease. PMID- 26141498 TI - [Characteristics of the patients "lost to follow-up" and determining factors of loss to follow-up to patients living with HIV at Ouagadougou, Burkina Faso]. AB - The objective of this study is to describe the characteristics of the patients "lost to follow-up" and determining factors of lost to follow-up at the patients infected by HIV. This is a descriptive and analytical retrospective study made on patients with or not by HAART, registered in the Day hospital of Ouagadougou. Of 5118 adult patients studied, 402 (7.9%) lost to follow-up. Among these patients, 340 (84.5%) had an unknown vital status, 28 (7%) were alive and 34 (8.5%) died. Mean age was 37.5 years. After active research, 16 from 21 patients under HAART were in treatment interruption. The main factors associated with the loss of follow-up were: no schooling (p=0,008), residing outside the capital (p=0,002) and being infected with HIV2 (p< 10(-3)). The phenomenon of loss of follow-up is important and concerned mainly not informed patients. PMID- 26141499 TI - [Serological and Behavioral Survey on HIV/AIDS among prisoners in Nouakchott (Mauritania)]. AB - In Mauritania, epidemiological data estimate national HIV prevalence to less than 1%. Our study is the first joint survey on HIV/AIDS conducted among prisoners in Mauritania. It is a cross-sectional survey with anonymity and informed consent. The study covered a sample of 296 prisoners enrolled in a population of 706 prisoners held in Nouakchott. The sex ratio was 14.6. The refusal rate of blood sample was 4.7%. HIV prevalence in the sample was 3.9%. 53.37% of prisoners knew the concept of seropositivity but only 7.4% had a perfect knowledge of the ways of HIV transmission untainted by false beliefs. The results showed that 99% of prisoners knew that the condom is a means of protection against HIV infection, but they also showed many false beliefs about protection against HIV in the majority of prisoners. Indeed, 98.49% of respondents said they protected themselves by avoiding sex with strangers and 94.97% of them thought that sex with young girls or virgins are protection against HIV. Nearly one quarter of the prisoners did not have a good perception of risk of contracting HIV in prison although homosexual relations between prisoners have been reported. This study showed that prisoners in Mauritania are a vulnerable group to HIV because the prevalence of HIV in this group was higher than the national prevalence and this sub-population was unfamiliar with the disease and adopt risk behaviors. PMID- 26141501 TI - Telepharmacy: Time to pick up the line. PMID- 26141500 TI - Construction of a Quality of Life Questionnaire for slowly progressive neuromuscular disease. AB - PURPOSE: To build a questionnaire to assess health-related quality of life (HRQL) in patients suffering from slowly progressive neuromuscular disease (NMD) using item response theory (IRT). METHODS: A pool of 64 items and a validated questionnaire (WHOQOL-BREF) were administered to 159 patients recruited in eight NMD referral centers. Exploratory statistical analysis included methods derived from both IRT and classical test theory. RESULTS: We constructed a questionnaire named QoL-NMD which is composed of two general items and 24 items classified in three domains: (1) "Impact of Physical Symptoms," (2) "Self-perception" and (3) "Activities and Social Participation." Each domain has good psychometric properties (Cronbach's alpha > 0.77, test-retest ICC > 0.81, Loevinger's H > 0.41) and meets IRT assumptions. Comparison with the WHOQOL-BREF enabled assessing similarities and discrepancies with a generic questionnaire. CONCLUSION: This study enabled the development of a new HRQL questionnaire specifically designed for slowly progressive NMD patients. The QoL-NMD is short enough to be used in clinical practice (26 items). The next steps will be to validate QoL-NMD by re-assessing psychometrics in an independent sample of patients and calibrate the IRT scoring system. PMID- 26141502 TI - Developing a primary care patient measure of safety (PC PMOS): a modified Delphi process and face validity testing. AB - BACKGROUND: Patients are a valuable source of information about ways to prevent harm in primary care and are in a unique position to provide feedback about the factors that contribute to safety incidents. Unlike in the hospital setting, there are currently no tools that allow the systematic capture of this information from patients. The aim of this study was to develop a quantitative primary care patient measure of safety (PC PMOS). METHODS: A two-stage approach was undertaken to develop questionnaire domains and items. Stage 1 involved a modified Delphi process. An expert panel reached consensus on domains and items based on three sources of information (validated hospital PMOS, previous research conducted by our study team and literature on threats to patient safety). Stage 2 involved testing the face validity of the questionnaire developed during stage 1 with patients and primary care staff using the 'think aloud' method. Following this process, the questionnaire was revised accordingly. RESULTS: The PC PMOS was received positively by both patients and staff during face validity testing. Barriers to completion included the length, relevance and clarity of questions. The final PC PMOS consisted of 50 items across 15 domains. The contributory factors to safety incidents centred on communication, access to care, patient related factors, organisation and care planning, task performance and information flow. DISCUSSION: This is the first tool specifically designed for primary care settings, which allows patients to provide feedback about factors contributing to potential safety incidents. The PC PMOS provides a way for primary care organisations to learn about safety from the patient perspective and make service improvements with the aim of reducing harm in this setting. Future research will explore the reliability and construct validity of the PC PMOS. PMID- 26141503 TI - Ranking hospitals on avoidable death rates derived from retrospective case record review: methodological observations and limitations. PMID- 26141504 TI - Ureteroduodenal fistula. AB - Ureteroduodenal fistula is a rare complication in urology. We report a case of 29 year-old man who presented with ureteroduodenal fistula. We have also discussed the management and treatment of this condition. PMID- 26141505 TI - Topological characterization of neuronal arbor morphology via sequence representation: II--global alignment. AB - BACKGROUND: The increasing abundance of neuromorphological data provides both the opportunity and the challenge to compare massive numbers of neurons from a wide diversity of sources efficiently and effectively. We implemented a modified global alignment algorithm representing axonal and dendritic bifurcations as strings of characters. Sequence alignment quantifies neuronal similarity by identifying branch-level correspondences between trees. RESULTS: The space generated from pairwise similarities is capable of classifying neuronal arbor types as well as, or better than, traditional topological metrics. Unsupervised cluster analysis produces groups that significantly correspond with known cell classes for axons, dendrites, and pyramidal apical dendrites. Furthermore, the distinguishing consensus topology generated by multiple sequence alignment of a group of neurons reveals their shared branching blueprint. Interestingly, the axons of dendritic-targeting interneurons in the rodent cortex associates with pyramidal axons but apart from the (more topologically symmetric) axons of perisomatic-targeting interneurons. CONCLUSIONS: Global pairwise and multiple sequence alignment of neurite topologies enables detailed comparison of neurites and identification of conserved topological features in alignment-defined clusters. The methods presented also provide a framework for incorporation of additional branch-level morphological features. Moreover, comparison of multiple alignment with motif analysis shows that the two techniques provide complementary information respectively revealing global and local features. PMID- 26141506 TI - Citronellol, a natural acyclic monoterpene, attenuates mechanical hyperalgesia response in mice: Evidence of the spinal cord lamina I inhibition. AB - We evaluated the anti-hyperalgesic effect of citronellol (CT) and investigated the spinal cord lamina I involvement in this effect. Male mice were pre-treated with CT (25, 50 and 100mg/kg, i.p.), indomethacin (10mg/kg, i.p.), dipyrone (60mg/kg, i.p.) or vehicle (saline+Tween 80 0.2%). Thirty minutes after the treatment, 20MUL of carrageenan (CG; 300MUg/paw), PGE2 (100ng/paw), dopamine (DA; 30MUg/paw) or TNF-alpha (100pg/paw) were injected into the hind paw subplantar region and the mechanical threshold was evaluated with an electronic anesthesiometer. The CT effect on edema formation was evaluated after the right paw subplantar injection of CG (40MUL; 1%) through the plethysmometer apparatus. To evaluate the CT action on the spinal cord, the animals were treated with CT (100mg/kg; i.p.) or vehicle (Saline+Tween 80 0.2%; i.p.) and, after 30min, 20MUL of CG (300MUg/paw; i.pl.) was injected. Ninety minutes after the treatment, the animals were perfused, the lumbar spinal cord collected, crioprotected, cut and submitted in an immunofluorescence protocol for Fos protein. CT administration produced a significantly reduction (p<0.05) in the mechanical hyperalgesia induced by CG, TNF-alpha, PGE2 and DA when compared with control group. The treatment with CT also significantly (p<0.05) decreased the paw edema. The immunofluorescence showed that the CT decrease significantly (p<0.05) the spinal cord lamina I activation. Thus, our results provide that CT attenuates the hyperalgesia, at least in part, through the spinal cord lamina I inhibition. PMID- 26141507 TI - MzJava: An open source library for mass spectrometry data processing. AB - Mass spectrometry (MS) is a widely used and evolving technique for the high throughput identification of molecules in biological samples. The need for sharing and reuse of code among bioinformaticians working with MS data prompted the design and implementation of MzJava, an open-source Java Application Programming Interface (API) for MS related data processing. MzJava provides data structures and algorithms for representing and processing mass spectra and their associated biological molecules, such as metabolites, glycans and peptides. MzJava includes functionality to perform mass calculation, peak processing (e.g. centroiding, filtering, transforming), spectrum alignment and clustering, protein digestion, fragmentation of peptides and glycans as well as scoring functions for spectrum-spectrum and peptide/glycan-spectrum matches. For data import and export MzJava implements readers and writers for commonly used data formats. For many classes support for the Hadoop MapReduce (hadoop.apache.org) and Apache Spark (spark.apache.org) frameworks for cluster computing was implemented. The library has been developed applying best practices of software engineering. To ensure that MzJava contains code that is correct and easy to use the library's API was carefully designed and thoroughly tested. MzJava is an open-source project distributed under the AGPL v3.0 licence. MzJava requires Java 1.7 or higher. Binaries, source code and documentation can be downloaded from http://mzjava.expasy.org and https://bitbucket.org/sib-pig/mzjava. This article is part of a Special Issue entitled: Computational Proteomics. PMID- 26141508 TI - Hemoglobin interacting proteins and implications of spectrin hemoglobin interaction. AB - In this report we have analyzed interacting partners of hemoglobin inside erythrocyte and sought possible implications of hemoglobin-spectrin interaction. Our list of identified cytosolic hemoglobin interacting proteins includes redox regulators like peroxiredoxin-2, Cu-Zn superoxide dismutase, catalase, aldehyde dehydrogenase-1, flavin reductase and chaperones like HSP70, alpha-hemoglobin stabilizing protein. Others include metabolic enzymes like carbonic anhydrase-1, selenium binding protein-1, purine nucleoside phosphorylase and nucleoside diphosphate kinase. Additionally, various membrane proteins like alpha and beta spectrin, ankyrin, band3, protein4.1, actin and glyceraldehyde 3 phosphate dehydrogenase have been shown to interact with hemoglobin. Our result indicates that major membrane skeleton protein spectrin, that also has a chaperone like activity, helps to fold the unstable alpha-globin chains in vitro. Taken together our results could provide insight into a protein network evolved around hemoglobin molecule inside erythrocyte that may add a new perspective in understanding the hemoglobin function and homeostasis. PMID- 26141509 TI - Imaging the D3 dopamine receptor across behavioral and drug addictions: Positron emission tomography studies with [(11)C]-(+)-PHNO. AB - Chronic drug use has been associated with dopaminergic abnormalities, detectable in humans with positron emission tomography (PET). Among these, a hallmark feature is low D2 dopamine receptor availability, which has been linked to clinical outcomes, but has not yet translated into a therapeutic strategy. The D3 dopamine receptor on the other hand has gained increasing attention, as, in contrast to D2, chronic exposure to drugs has been shown to up-regulate this receptor subtype in preclinical models of addiction-a phenomenon linked to dopamine system sensitization and drug-seeking. The present article summarizes the literature to date in humans, suggesting that the D3 receptor may indeed contribute to core features of addiction such as impulsiveness and cognitive impairment. A particularly useful tool in investigating this question is the PET imaging probe [(11)C]-(+)-PHNO, which binds to D2/3 dopamine receptors but has preferential affinity for D3. This technique has been used to demonstrate D3 up regulation in humans, and can be applied to assess pharmacological interventions for development of D3-targeted strategies in addiction treatment. PMID- 26141510 TI - Different physiological and behavioural effects of e-cigarette vapour and cigarette smoke in mice. AB - Nicotine is the primary addictive substance in tobacco smoke and electronic cigarette (e-cig) vapour. Methodological limitations have made it difficult to compare the role of the nicotine and non-nicotine constituents of tobacco smoke. The aim of this study was to compare the effects of traditional cigarette smoke and e-cig vapour containing the same amount of nicotine in male BALB/c mice exposed to the smoke of 21 cigarettes or e-cig vapour containing 16.8 mg of nicotine delivered by means of a mechanical ventilator for three 30-min sessions/day for seven weeks. One hour after the last session, half of the animals were sacrificed for neurochemical analysis, and the others underwent mecamylamine-precipitated or spontaneous withdrawal for the purposes of behavioural analysis. Chronic intermittent non-contingent, second-hand exposure to cigarette smoke or e-cig vapour led to similar brain cotinine and nicotine levels, similar urine cotinine levels and the similar up-regulation of alpha4beta2 nicotinic acetylcholine receptors in different brain areas, but had different effects on body weight, food intake, and the signs of mecamylamine precipitated and spontaneous withdrawal episodic memory and emotional responses. The findings of this study demonstrate for the first time that e-cig vapour induces addiction-related neurochemical, physiological and behavioural alterations. The fact that inhaled cigarette smoke and e-cig vapour have partially different dependence-related effects indicates that compounds other than nicotine contribute to tobacco dependence. PMID- 26141512 TI - Fgfr2 is required for the expansion of the early adrenocortical primordium. AB - The adrenal cortex is a critical steroidogenic endocrine tissue, generated at least in part from intermediate mesoderm of the anterior urogenital ridge. Previous work has pinpointed a minor role of the FGFR2IIIb isoform in expansion and differentiation of the fetal adrenal cortex in mice but did not address the complete role of FGFR2 and FGFR1 signaling in adrenocortical development. Here, we show that a Tbx18(cre) line mediates specific recombination in the coelomic epithelium of the anterior urogenital ridge which gives rise by a delamination process to the adrenocortical primordium. Mice with conditional (Tbx18(cre) mediated) deletion of all isoforms of Fgfr2 exhibited severely hypoplastic adrenal glands around birth. Cortical cells were dramatically reduced in number but showed steroidogenic differentiation and zonation. Neuroendocrine chromaffin cells were also reduced and formed a cell cluster adjacent to but not encapsulated by steroidogenic cells. Analysis of earlier time points revealed that the adrenocortical primordium was established in the intermediate mesoderm at E10.5 but that it failed to expand at subsequent stages. Our further experiments show that FGFR2 signaling acts as early as E11.5 to prevent apoptosis and enhance proliferation in adrenocortical progenitor cells. FGFR1 signaling does not contribute to early adrenocortical development. Our work suggests that FGFR2IIIb and IIIc isoforms largely act redundantly to promote expansion of the adrenocortical primordium. PMID- 26141511 TI - An analysis of moderators in the COMBINE study: Identifying subgroups of patients who benefit from acamprosate. AB - The goal of the current study was to use tree-based methods to identify moderators of acamprosate effect on abstinence from heavy drinking in COMBINE, the largest study of pharmacotherapy for alcoholism in the United States to date. We used three different tree-based methods for identification of subgroups with enhanced treatment response on acamprosate based on over 100 predictors measured at baseline in COMBINE. No heavy drinking during the last two months of treatment was the considered outcome. All three methods identified consecutive days of abstinence prior to treatment as the most important moderator of treatment effect. Acamprosate was beneficial for participants with shorter abstinence (1 week or less) especially when body mass index was low or normal. In this group, 46% of participants receiving active acamprosate abstained from heavy drinking compared to 23% of those receiving placebo acamprosate. Prior treatment, age, drinking goal and cognitive inefficiency were identified as moderators of acamprosate effects by one of the three methods. In conclusion, acamprosate may be beneficial for participants with shorter abstinence who are not overweight or obese. One hypothesis for this finding is that this subgroup may have greater glutamatergic hyperactivity, a target of acamprosate, and may achieve better drug plasma levels based on their lower BMI. In contrast, those with extended pretreatment abstinence who have an otherwise good prognosis did not benefit from acamprosate. Further validation of the results in independent data sets is necessary. PMID- 26141513 TI - First occurrence of Cedrelospermum (Ulmaceae) in Asia and its biogeographic implications. AB - Cedrelospermum (Ulmaceae) is an extinct genus with extensive fossil records in Europe and North America. However, no fossil of the genus has been reported from Asia. Here we describe Cedrelospermum asiaticum L.B. Jia, Y.J. Huang et Z.K. Zhou sp. nov. based on compressed fruits from the late Miocene of Yunnan, southwestern China. The fossil fruits are characterized by an ovate fruit body adjoined by double wings, with the veins on the primary wing converging toward a stigmatic area. According to the historical geographic distribution of the genus, we hypothesize that Cedrelospermum originated in North America where both single winged and double-winged fruits were reported. The single-winged form subsequently spread into Europe via the North Atlantic land bridge and the double winged form dispersed into Asia via the Bering land bridge. From the Eocene to Oligocene, a southward retreat of the genus distribution probably took place, which coincided with the global surface cooling initiated during the Eocene Oligocene transition. The extinction of Cedrelospermum from Asia may be related to the intensification of the East Asian monsoon. PMID- 26141514 TI - Systemic immunity shapes the oral microbiome and susceptibility to bisphosphonate associated osteonecrosis of the jaw. AB - BACKGROUND: Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug effect linked to long-term and/or high-dose exposure to nitrogen-bisphosphonates (N-BP), the standard of care for the treatment of bone fragility disorders. The mechanism leading to bisphosphonate-associated ONJ (BAONJ) is unclear and optimal treatment strategies are lacking. Recent evidence suggests that BAONJ may be linked to drug-induced immune dysfunction, possibly associated with increased susceptibility to infections in the oral cavity. The objective of this investigation was to comprehensively assess the relationship linking immune function, N-BP exposure, the oral microbiome and ONJ susceptibility. METHODS: Leukocyte gene expression of factors important for immunity, wound healing and barrier function were assessed by real-time quantitative PCR and the oral microbiome was characterized by 454 pyrosequencing of the 16S rRNA gene in 93 subjects stratified by N-BP exposure and a history of ONJ. RESULTS: There were marked differences in the systemic expression of genes regulating immune and barrier functions including RANK (p = 0.007), aryl hydrocarbon receptor (AHR, p < 0.001), and FGF9 (p < 0.001), which were collectively up-regulated in individuals exposed to N-BP without ONJ relative to treatment controls. In contrast, the expression levels of these same genes were significantly down-regulated in those who had experienced BAONJ. Surprisingly, the oral microbiome composition was not directly linked to either BAONJ or N-BP exposure, rather the systemic leukocyte expression levels of RANK, TNFA and AHR each explained 9% (p = 0.04), 12% (p = 0.01), and 7% (p = 0.03) of the oral bacterial beta diversity. CONCLUSIONS: The oral microbiome is unlikely causative of ONJ, rather individuals with BAONJ lacked immune resiliency which impaired their capacity to respond adequately to the immunological stress of N-BP treatment. This may be the common factor linking N-BP and anti-RANK agents to ONJ in at-risk individuals. Preventive and/or therapeutic strategies should target the wound healing deficits present in those with ONJ. PMID- 26141516 TI - Mutual blood donation is safer at small blood collection stations in China. AB - BACKGROUND: The assumption that the level of safety of voluntary non-remunerated donors is significantly higher than that of family replacement donors is supported by global data without stratifying for first-time or repeat volunteer, or according to age, but the viral marker prevalence between replacement donors and first-time voluntary non-remunerated donors is similar. MATERIALS AND METHODS: From 2006 to 2013, replacement and voluntary donors were respectively recruited by the hospitals and the Center Blood Station in Zhaoqing, Guangdong, according to the existing procedures, and all the donors were screened for hepatitis B virus (HBV) surface antigen (HBsAg), antibodies against hepatitis C virus (anti-HCV), human immunodeficiency virus (anti-HIV) (1 + 2) and Treponema pallidum (anti-TP) by the enzyme immunoassays (EIAs), and alanine aminotransferase (ALT) in the Center Blood Station by kinetic analysis method. The risk factors related to blood safety were analyzed by Binary logistic regression analysis. RESULTS: Between 252,202 volunteers and 2771 replacement donors, the prevalences of ALT > 40 U/L and anti-HIV (4.88% and 0.01% vs 4.44% and 0.07%, respectively) were not significantly different. The prevalences of HBsAg, anti-HCV and anti-syphilis in replacement group were higher than those in voluntary group, which were related to donor's sex, age and donation time. Overall prevalence of serological markers was higher in male replacement donors than in female, and in replacement donor over 30 years than in those below 30 years, but the positive prevalence in repeated replacement donors was lower than that in first-time replacement donors. CONCLUSIONS: With appropriate intervention measures, such as pre-donor screening and other donor selection policy, replacement donors and voluntary donors provide a similar level of viral safety. Our donor selection policy in future should focus on retaining both young replacement and young voluntary donors as repeat donors and promoting the donation proportion of females, which will improve blood safety. PMID- 26141515 TI - mirEX 2.0 - an integrated environment for expression profiling of plant microRNAs. AB - BACKGROUND: MicroRNAs are the key post-transcriptional regulators of gene expression in development and stress responses. Thus, precisely quantifying the level of each particular microRNA is of utmost importance when studying the biology of any organism. DESCRIPTION: The mirEX 2.0 web portal ( http://www.combio.pl/mirex ) provides a comprehensive platform for the exploration of microRNA expression data based on quantitative Real Time PCR and NGS sequencing experiments, covering various developmental stages, from wild-type to mutant plants. The portal includes mature and pri-miRNA expression levels detected in three plant species (Arabidopsis thaliana, Hordeum vulgare and Pellia endiviifolia), and in A. thaliana miRNA biogenesis pathway mutants. In total, the database contains information about the expression of 461 miRNAs representing 268 families. The data can be explored through the use of advanced web tools, including (i) a graphical query builder system allowing a combination of any given species, developmental stages and tissues, (ii) a modular presentation of the results in the form of thematic windows, and (iii) a number of user-friendly utilities such as a community-building discussion system and extensive tutorial documentation (e.g., tooltips, exemplary videos and presentations). All data contained within the mirEX 2.0 database can be downloaded for use in further applications in a context-based way from the result windows or from a dedicated web page. CONCLUSIONS: The mirEX 2.0 portal provides the plant research community with easily accessible data and powerful tools for application in multi conditioned analyses of miRNA expression from important plant species in different biological and developmental backgrounds. PMID- 26141517 TI - Gremlin is a key pro-fibrogenic factor in chronic pancreatitis. AB - The current study aims to identify the pro-fibrogenic role of Gremlin, an endogenous antagonist of bone morphogenetic proteins (BMPs) in chronic pancreatitis (CP). CP is a highly debilitating disease characterized by progressive pancreatic inflammation and fibrosis that ultimately leads to exocrine and endocrine dysfunction. While transforming growth factor (TGF)-beta is a known key pro-fibrogenic factor in CP, the TGF-beta superfamily member BMPs exert an anti-fibrogenic function in CP as reported by our group recently. To investigate how BMP signaling is regulated in CP by BMP antagonists, the mouse CP model induced by cerulein was used. During CP induction, TGF-beta1 messenger RNA (mRNA) increased 156-fold in 2 weeks, a BMP antagonist Gremlin 1 (Grem1) mRNA levels increased 145-fold at 3 weeks, and increases in Grem1 protein levels correlated with increases in collagen deposition. Increased Grem1 was also observed in human CP pancreata compared to normal. Grem1 knockout in Grem1 (+/-) mice revealed a 33.2 % reduction in pancreatic fibrosis in CP compared to wild type littermates. In vitro in isolated pancreatic stellate cells, TGF-beta induced Grem1 expression. Addition of the recombinant mouse Grem1 protein blocked BMP2-induced Smad1/5 phosphorylation and abolished BMP2's suppression effects on TGF-beta-induced collagen expression. Evidences presented herein demonstrate that Grem1, induced by TGF-beta, is pro-fibrogenic by antagonizing BMP activity in CP. KEY MESSAGES: * Gremlin is upregulated in human chronic pancreatitis and a mouse CP model in vivo. * Deficiency of Grem1 in mice attenuates pancreatic fibrosis under CP induction in vivo. * TGF-beta induces Gremlin mRNA and protein expression in pancreatic stellate cells in vitro. * Gremlin blocks BMP2 signaling and function in pancreatic stellate cells in vitro. * This study discloses a pro fibrogenic role of Gremlin by antagonizing BMP activity in chronic pancreatitis. PMID- 26141518 TI - Natural lignans from Arctium lappa as antiaging agents in Caenorhabditis elegans. AB - Arctium lappa is a well-known traditional medicinal plant in China (TCM) and Europe that has been used for thousands of years to treat arthritis, baldness or cancer. The plant produces lignans as secondary metabolites, which have a wide range of bioactivities. Yet, their antiaging potential has not been explored. In this study, we isolated six lignans from A. lappa seeds, namely arctigenin, matairesinol, arctiin, (iso)lappaol A, lappaol C, and lappaol F. The antioxidant and antiaging properties of the isolated lignans were studied using Caenorhabditis elegans as a relevant animal model. All lignans at concentrations of 10 and 100 MUM significantly extended the mean life span of C. elegans. The strongest effect was observed with matairesinol, which at a concentration of 100 MUM extended the life span of worms by 25%. Additionally, we observed that five lignans are strong free radical-scavengers in vitro and in vivo and all lignans can improve survival of C. elegans under oxidative stress. Furthermore, the lignans can induce the nuclear translocation of the transcription factor DAF-16 and up-regulate its expression, suggesting that a possible underlying mechanism of the observed longevity-promoting activity of lignans depends on DAF-16 mediated signaling pathway. All lignans up-regulated the expression of jnk-1, indicating that lignans may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade. Our study reports new antiaging activities of lignans, which might be candidates for developing antiaging agents. PMID- 26141519 TI - Impact of aflatoxin B1 on hypothalamic neuropeptides regulating feeding behavior. AB - The presence of mycotoxins in food is a major problem of public health as they produce immunosuppressive, hepatotoxic and neurotoxic effects. Mycotoxins also induce mutagenic and carcinogenic effects after long exposure. Among mycotoxins that contaminate food are aflatoxins (AF) such as AFB1, which is the most powerful natural carcinogen. The AF poisoning results in symptoms of depression, anorexia, diarrhea, jaundice or anemia that can lead to death, but very few studies have explored the impact of AF on neuroendocrine regulations. To better understand the neurotoxic effects of AF related to anorexia, we explored in rat the impact of AFB1 on the major hypothalamic neuropeptides regulating feeding behavior, either orexigenic (NPY, Orexin, AgRP, MCH) or anorexigenic (alpha-MSH, CART, TRH). We also studied the effect of AFB1 on a novel neuropeptide, the secretogranin II (SgII)-derived peptide EM66, which has recently been linked to the control of food intake. For this, adult male rats were orally treated twice a week for 5 weeks with a low dose (150 MUg/kg) or a high dose (300 MUg/kg) of AFB1 dissolved in corn oil. Repeated exposure to AFB1 resulted in reduced body weight gain, which was highly significant for the high dose of AF. Immunocytochemical and quantitative PCR experiments revealed a dose-related decrease in the expression of all the hypothalamic neuropeptides studied in response to AFB1. Such orexigenic and anorexigenic alterations may underlie appetite disorders as they are correlated to a dose-dependent decrease in body weight gain of treated rats as compared to controls. We also found a decrease in the number of EM66 containing neurons in the arcuate nucleus of AFB1-treated animals, which was associated with a lower expression of its precursor SgII. These findings show for the first time that repeated consumption of AFB1 disrupts the hypothalamic regulation of neuropeptides involved in feeding behavior, which may contribute to the lower body weight gain associated to AF exposure. PMID- 26141521 TI - Billing and Record-Keeping for Familial Cancer Risk Counseling: A National Survey. AB - We surveyed 111 genetic counselors providing cancer risk counseling (CRC) in order to document their billing and record-keeping practices. Of the 75 respondents, billing was generally done under the supervising physician with a wide variation in charges. Follow-up telephone interviews with 28 counselors who charge patients revealed that billing was usually done using the CPT codes for consultations, and the ICD-9 diagnostic codes for cancer (if applicable), a medical complaint, or a family history of cancer code. Most counselors exclude some clinical information from the patient's medical record. In consultation notes, 81% of counselors document a discussion of genetic testing, but only 37% document the patient's actual testing decision, and only 19% document test results. In anticipation of increased referrals for CRC, data are needed on the components of a CRC visit, the amount of time required to provide CRC, patient outcomes measures, and charges and reimbursement. The feasibility and advisability of keeping results separate from the patient's medical record also needs to be addressed. PMID- 26141520 TI - Alterations in mitochondrial dynamics induced by tebufenpyrad and pyridaben in a dopaminergic neuronal cell culture model. AB - Tebufenpyrad and pyridaben are two agro-chemically important acaricides that function like the known mitochondrial toxicant rotenone. Although these two compounds have been commonly used to kill populations of mites and ticks in commercial greenhouses, their neurotoxic profiles remain largely unknown. Therefore, we investigated the effects of these two pesticides on mitochondrial structure and function in an in vitro cell culture model using the Seahorse bioanalyzer and confocal fluorescence imaging. The effects were compared with rotenone. Exposing rat dopaminergic neuronal cells (N27 cells) to tebufenpyrad and pyridaben for 3h induced dose-dependent cell death with an EC50 of 3.98MUM and 3.77MUM, respectively. Also, tebufenpyrad and pyridaben (3MUM) exposure induced reactive oxygen species (ROS) generation and m-aconitase damage, suggesting that the pesticide toxicity is associated with oxidative damage. Morphometric image analysis with the MitoTracker red fluorescent probe indicated that tebufenpyrad and pyridaben, as well as rotenone, caused abnormalities in mitochondrial morphology, including reduced mitochondrial length and circularity. Functional bioenergetic experiments using the Seahorse XF96 analyzer revealed that tebufenpyrad and pyridaben very rapidly suppressed the basal mitochondrial oxygen consumption rate similar to that of rotenone. Further analysis of bioenergetic curves also revealed dose-dependent decreases in ATP-linked respiration and respiratory capacity. The luminescence-based ATP measurement further confirmed that pesticide-induced mitochondrial inhibition of respiration is accompanied by the loss of cellular ATP. Collectively, our results suggest that exposure to the pesticides tebufenpyrad and pyridaben induces neurotoxicity by rapidly initiating mitochondrial dysfunction and oxidative damage in dopaminergic neuronal cells. Our findings also reveal that monitoring the kinetics of mitochondrial respiration with Seahorse could be used as an early neurotoxicological high-throughput index for assessing the risk that pesticides pose to the dopaminergic neuronal system. PMID- 26141522 TI - Genetic Counseling, Reproductive Behavior and Future Reproductive Intentions of People with Neurofibromatosis Type 1 (NF1). AB - Neurofibromatosis type 1(NF1) is a complex and variable inherited disorder. The complexity and variability present particular difficulty for genetic counseling. Thirty-three people with NF1 of reproductive age were interviewed about their experience of genetic counseling, their past reproductive behavior and future intentions. One third reported having had no genetic counseling or not having it until after their first child. In part, this may be due to delay in diagnosis but also indicates poor access to genetic services. Only three people had ever been offered prenatal genetic testing and only one had accepted. Although testing is still technically difficult, the greatest deterrent to uptake of prenatal testing for NF1 is the variability of the disorder. However, six of the 17 people planning future pregnancies would want a test with a view to termination if necessary. Others would welcome testing in order to be prepared but not to terminate. We discuss some of the factors which influence reproductive decision making for people with NF1 and some of the difficulties in genetic counseling in such a variable and complex disorder. PMID- 26141523 TI - Women's Understanding of Their Risk of Developing Breast/Ovarian Cancer Before and After Genetic Counseling. AB - Many studies have reported that individuals frequently over- or underestimate their risk of developing cancer both before and after they attend genetic counseling for breast and/or ovarian cancer. Using a combination of interviews and written questionnaires, we investigated counselees' understanding of their risk of developing cancer before and after genetic counseling. We demonstrate that although 76% of the sample thought that their risk was elevated relative to women in general, only a small proportion (17%) were willing or able to provide a numerical estimate of their risk of developing cancer before they attended the clinic. Following the consultation, 43% indicated that their risk of developing cancer was lower than they had anticipated. Twenty-two percent described their risk in absolute rather than relative terms, i.e., that they would definitely (not) develop cancer in the future. The implications of these findings for further research are discussed. PMID- 26141524 TI - Genetic Library. PMID- 26141525 TI - Isolation, purification and characterization of novel antimicrobial compound 7 methoxy-2,2-dimethyl-4-octa-4',6'-dienyl-2H-napthalene-1-one from Penicillium sp. and its cytotoxicity studies. AB - Fungus isolated from soil has been evaluated for its antimicrobial activity which showed broad spectrum antimicrobial activity against all the pathogenic microorganisms used. Optimization was done by response surface methodology (RSM) to further optimize the medium which could further enhance the antimicrobial activity by 1.1-1.9 folds. Column chromatography was used to isolate the active compound which was characterized to be by various spectroscopic techniques such NMR, IR and LCMS and it was found to be apparently novel compound 7-methoxy-2,2 dimethyl-4-octa-4',6'-dienyl-2 H -napthalene-1-one. MIC of the active compound ranged from (0.5-15 ug/mL which was found to be comparable with the standard antibiotics. Viable cell count studies of the active compound showed it to be bactericidal in nature. Further, the compound when tested for its biosafety was found neither to be cytotoxic nor mutagenic. Cytotoxicity studies of the compound on cancer cell lines showed a valuable cytotoxic potential against all tested human cancer cell lines. Further, the compound induces apoptosis in lung cancer (A549) cells reveled by increase the distribution of nuclear DNA in Sub G1 phase as observed in flow cytometry. The study demonstrated that an apparently novel compound isolated from Penicillium sp. seems to be a stable and potent antimicrobial. PMID- 26141526 TI - Defining the real-world reproducibility of visual grading of left ventricular function and visual estimation of left ventricular ejection fraction: impact of image quality, experience and accreditation. AB - Left ventricular function can be evaluated by qualitative grading and by eyeball estimation of ejection fraction (EF). We sought to define the reproducibility of these techniques, and how they are affected by image quality, experience and accreditation. Twenty apical four-chamber echocardiographic cine loops (Online Resource 1-20) of varying image quality and left ventricular function were anonymized and presented to 35 operators. Operators were asked to provide (1) a one-phrase grading of global systolic function (2) an "eyeball" EF estimate and (3) an image quality rating on a 0-100 visual analogue scale. Each observer viewed every loop twice unknowingly, a total of 1400 viewings. When grading LV function into five categories, an operator's chance of agreement with another operator was 50% and with themself on blinded re-presentation was 68%. Blinded eyeball LVEF re-estimates by the same operator had standard deviation (SD) of difference of 7.6 EF units, with the SD across operators averaging 8.3 EF units. Image quality, defined as the average of all operators' assessments, correlated with EF estimate variability (r = -0.616, p < 0.01) and visual grading agreement (r = 0.58, p < 0.01). However, operators' own single quality assessments were not a useful forewarning of their estimate being an outlier, partly because individual quality assessments had poor within-operator reproducibility (SD of difference 17.8). Reproducibility of visual grading of LV function and LVEF estimation is dependent on image quality, but individuals cannot themselves identify when poor image quality is disrupting their LV function estimate. Clinicians should not assume that patients changing in grade or in visually estimated EF have had a genuine clinical change. PMID- 26141527 TI - What score on the Vancouver Scar Scale constitutes a hypertrophic scar? Results from a survey of North American burn-care providers. AB - INTRODUCTION: Reliable characterization of a hypertrophic scar (HTS) is integral to epidemiologic studies designed to identify clinical and genetic risk factors for HTS. The Vancouver Scar Scale (VSS) has been widely used for this purpose; however, no publication has defined what score on this scale corresponds to a clinical diagnosis of HTS. METHODS: In a survey of 1000 burn care providers, we asked respondents what VSS score indicates a HTS and asked them to score scar photos using the VSS. We used receiver-operating-characteristic (ROC) curves to evaluate VSS sub-scores and their combinations in diagnosis of HTS. RESULTS: Of 130 responses (13.5%), most were physicians (43.9%) who had worked in burn care for over 10 years (63.1%) and did not use the VSS in clinical practice (58.5%). There was no consensus as to what VSS score indicates a diagnosis of HTS. VSS height score (0-3) performed best for diagnosis of HTS; using a cut-off of >=1, height score was 99.5% sensitive and 85.9% specific for HTS. CONCLUSIONS: Burn clinicians do not routinely use the VSS and perceptions vary widely regarding what constitutes a HTS. When a dichotomous variable is needed, the VSS height score with a cut-off of >=1 may be optimal. Our findings underscore the need for an objective tool to reproducibly characterize HTS across burn centers. PMID- 26141528 TI - A study of mobile phone use among patients with noncommunicable diseases in La Paz, Bolivia: implications for mHealth research and development. AB - BACKGROUND: While global momentum supporting mobile health (mHealth) research and development is increasing, it is imperative to assess the potential fit of mHealth programs in local settings. We describe the penetration of mobile technologies among Bolivian patients with noncommunicable diseases (NCDs) to inform research on mHealth interventions for the Andean region as well as low- and middle-income countries more generally. METHODS: Five-hundred and fifty-nine NCD patients were identified from outpatient clinics affiliated with four hospitals in the cities of La Paz and El Alto. Respondents completed surveys about their use of standard mobile phones and smartphones. Respondents also provided information about their sociodemographic characteristics, health status, and access to care. We used descriptive statistics and logistic regression to understand the variation in mobile phone use across groups defined by patient characteristics associated with health service access and socioeconomic vulnerability. RESULTS: Respondents were on average 52 years of age, 33% had at most a sixth grade education, and 30% spoke an indigenous language in their home. Eighty-six percent owned a mobile phone and 13% owned a smartphone. Fifty-eight percent of mobile phone users sent or received a text message at least once a week. Some mobile phone owners reported connectivity problems, such as lacking mobile signal (9%) or credit to make a call (17%). Younger age, male gender, high health literacy, more years of education, and having fewer previously diagnosed NCDs were positively related to mobile phone ownership. Among mobile phone users, respondents with lower education and other indicators of vulnerability were less likely than their counterparts to report frequent usage of texting services. CONCLUSIONS: Mobile phones have high penetration among NCD patients in La Paz, Bolivia, including among those who are older, less educated, and who have other socioeconomic risk factors. Smartphone use is still relatively uncommon, even among patients who are younger and more educated. While certain patient characteristics such as age or education impact patients' use of text messaging, mobile phone-based mHealth interventions are feasible strategies for increasing NCD patients' access to self-management support between face-to-face clinical encounters. PMID- 26141529 TI - Losartan: A new treatment for cardiac cachexia? PMID- 26141530 TI - Prolonged Cre expression driven by the alpha-myosin heavy chain promoter can be cardiotoxic. AB - Studying the importance of genetic factors in a desired cell type or tissue necessitates the use of precise genetic tools. With the introduction of bacteriophage Cre recombinase/loxP mediated DNA editing and promoter-specific Cre expression, it is feasible to generate conditional knockout mice in which particular genes are disrupted in a cell type-specific manner in vivo. In cardiac myocytes, this is often achieved through alpha-myosin heavy chain promoter (alphaMyHC)-driven Cre expression in conjunction with a loxP-site flanked gene of interest. Recent studies in other cell types demonstrate toxicity of Cre expression through induction of DNA damage. However, it is unclear to what extent the traditionally used alphaMyHC-Cre line [1] may exhibit cardiotoxicity. Further, the genotype of alphaMyHC-Cre(+/-) is not often included as a control group in cardiac myocyte-specific knockout studies. Here we present evidence that these alphaMyHC-Cre(+/-) mice show molecular signs of cardiac toxicity by 3months of age and exhibit decreased cardiac function by 6months of age compared to wild type littermates. Hearts from alphaMyHC-Cre(+/-) mice also display evidence of fibrosis, inflammation, and DNA damage. Interestingly, some of the early functional changes observed in alphaMyHC-Cre(+/-) mice are sexually dimorphic. Given the high level of Cre recombinase expression resulting from expression from the alphaMyHC promoter, we asked if degenerate loxP-like sites naturally exist in the mouse genome and if so, whether they are affected by Cre in the absence of canonical loxP-sites. Using a novel bioinformatics search tool, we identified 619 loxP-like sites with 4 or less mismatches to the canonical loxP-site. 227 sites overlapped with annotated genes and 55 of these genes were expressed in cardiac muscle. Expression of ~26% of the 27 genes tested was disrupted in alphaMyHC Cre(+/-) mice indicating potential targeting by Cre. Taken together, these results highlight both the importance of using alphaMyHC-Cre mice as controls in conditional knockout studies as well as the need for a less cardiotoxic Cre driver for the field. PMID- 26141531 TI - Analysis of porcine granulosa cell death signaling pathways induced by vinclozolin. AB - Recent studies suggest that disturbing androgen-signaling pathways in porcine ovarian follicles may cause granulosa cell (GC) death. For this reason, we investigated which apoptotic pathway is initiated after GC exposure to an environmental antiandrogen, vinclozolin (Vnz), in vitro. Immunocytochemistry, Western blots, and fluorometric assays were used to quantify caspase-3 and -9 expression and activity. To elucidate the specific mechanism of Vnz action and toxicity, GCs were assessed for viability, cytotoxicity, and apoptotic activity using the ApoTox-Glo Triplex Assay. To further determine the mechanism of GC death induced by Vnz, we used the Apoptosis Antibody Array Kit. In response to Vnz stimulus, we found an increased level of caspase-3 protein expression (P <= 0.001) and an increase in caspase-3 proteolytic activity (P <= 0.001), confirming that Vnz is a potent proapoptotic factor. The strong immunoreaction of caspase-9 after Vnz treatment (P <= 0.001) suggests that intrinsic mitochondrial apoptosis pathway was activated during GC death. On the other hand, caspase-8, being a part of the extrinsic receptor pathway, was also activated (P <= 0.001). Therefore, it is possible that Vnz induces porcine granulosal apoptosis also through a parallel pathway. Activation of these two pathways was confirmed by the Apoptosis Antibody Array Kit. In conclusion, it is possible that the intrinsic signaling pathway may not act as an initial trigger for GC apoptosis but might contribute to the amplification and propagation of apoptotic cell death in the granulosa layer after treatment with this antiandrogen. Moreover, Vnz disturbs the physiological process of programmed cell death. Consequently, this could explain why atretic follicles are rapidly removed and suggests that normal function of the ovarian follicle may be destroyed. PMID- 26141532 TI - Comparison of 4- versus 5-day Co-Synch + controlled internal drug release (CIDR) + timed artificial insemination protocols in dairy heifers. AB - The objective of this study was to compare the pregnancy rate after timed artificial insemination (P/TAI) in dairy heifers treated with 4- versus 5-day Co Synch + controlled internal drug release (CIDR) protocols. A total of 120 Holstein heifers were randomly assigned to one of two groups. The heifers received an intravaginal CIDR insert containing 1.38 g of progesterone for 4 days (Monday-Friday 4-day Co-Synch + CIDR; n = 60) or 5 days (5-day Co-Synch + CIDR; n = 60). At the time of CIDR removal, 25 mg of PGF2alpha was injected intramuscularly, and 72 hours after CIDR removal, the heifers received 100 MUg of GnRH intramuscularly and were artificially inseminated. Artificial insemination was performed by an experienced technician, using commercial frozen-thawed semen from a single sire. Pregnancy diagnosis was performed by ultrasonography per rectum 32 days after TAI. Categorical data were analyzed using proc logistic and the chi-square test, whereas continuous variables were analyzed using the t-test of Statistical Analysis Systems. Heifers in the 4-day Co-Synch + CIDR group had an acceptable P/TAI32 (55.0%, 33 of 60), which was not different (P = 0.35) from that observed in the 5-day Co-Synch + CIDR group (63.3%, 38 of 60). Progesterone concentration at CIDR insertion or estradiol concentration at TAI did not influence the pregnancy outcomes. Interestingly, estradiol concentration at TAI was greater in the 4-day Co-Synch + CIDR group compared to the 5-day Co-Synch + CIDR group (P < 0.01). In conclusion, the Monday to Friday 4-day Co-Synch + CIDR protocol resulted in adequate P/TAI in dairy heifers, which was similar to that of the 5-day Co-Synch + CIDR protocol. This novel protocol might represent a promising hormonal treatment for TAI in dairy heifers, facilitating their reproductive management routine, while maintaining an adequate fertility. PMID- 26141533 TI - Factors Associated with Colostrum Avoidance Among Mothers of Children Aged less than 24 Months in Raya Kobo district, North-eastern Ethiopia: Community-based Cross-sectional Study. AB - BACKGROUND: UNICEF and WHO recommend colostrum as newborns' perfect food that should be initiated within the first hour after birth. OBJECTIVE: To assess colostrum avoidance practices and associated factors among mothers of children aged <24 months in Raya Kobo district, North-eastern Ethiopia. METHODS: A quantitative community-based cross-sectional study supplemented by qualitative method was used. Descriptive statistics, binary and multivariable logistic regression analyses were used in the statistical analysis. RESULTS: Colostrum avoidance was practiced by 13.5% (95% confidence interval: 10.99-16.33) of mothers having children aged <24 months. In multivariable logistic regression analysis, giving birth at home, mother-heading households, lack of awareness on the advantages of colostrum and late initiation of breastfeeding remained statistically significant factors associated with colostrum avoidance practices. CONCLUSION: Promoting institutional delivery, timely initiation of breastfeeding and creating awareness on the advantages of colostrum feeding are recommended interventions to reduce colostrum avoidance. PMID- 26141534 TI - Influence of vertebral column distraction on spinal cord volume: an experimental study in a goat model. AB - INTRODUCTION: Spinal cord injury may be related to excessive distraction of the spinal cord during surgical correction of spinal deformities by vertebral column resection. This study aimed to investigate how vertebral column distraction influences spinal cord volume to establish the safe range in a goat model. MATERIALS AND METHODS: A vertebral column resection was performed on the tenth thoracic vertebra of 11 goats. The spinal cord was distracted until the somatosensory evoked potential signals were decreased to 50 % from baseline amplitude or were delayed by 10 % of the baseline peak latency. The osteotomy segment was stabilized with a PEEK mesh cage filled with bone graft, and the pedicle screws on the rods were then tightened in this position. Spinal cord volume was calculated using Mimics software, and T10 height, disk height, osteotomy segment height, and spinal segment height were measured using the MRI image workstation. RESULTS: Three goats were excluded, and data obtained from the eight remaining goats were analyzed. The safe limit of distraction distance was 11.8 +/- 3.65 mm, and the distraction distance was strongly correlated with the difference between the pre- and postoperative measurements (d value) of spinal cord volume per 1 mm of osteotomy segment height (r = -0.952, p < 0.001), but was not correlated with T10 body height (r = 0.16, p = 0.71), spinal segment height (r = 0.29, p = 0.49), disk height (r = -0.12, p = 0.98), or the d value (pre post) of spinal cord volume per 1 mm of spinal segment height (r = 0.45, p = 0.26). The mean d value (pre-post) of spinal cord volume per 1 mm of osteotomy segment height was 10.05 +/- 0.02 mm(3) (range 10.02-10.08 mm(3)). CONCLUSION: The maximum change in spinal cord volume per 1-mm change in height was in the osteotomy segment, and its safe limit was 10.05 +/- 0.02 mm(3). The safe limit of spinal cord distraction can be calculated using the spinal cord volume per unit 1 mm change in height. PMID- 26141535 TI - Temperature-controlled continuous cold flow device versus traditional icing regimen following anterior cruciate ligament reconstruction: a prospective randomized comparative trial. AB - INTRODUCTION: Anterior cruciate ligament (ACL) reconstruction requires an intensive rehabilitation program to be completely successful. Cryotherapy has been described to be helpful in reducing post-operative pain and edema. Aim of this prospective randomized study is to compare two homogeneous groups of patients, one receiving traditional icing regimen and the other a temperature controlled continuous cold flow device, in post-operative setting after ACL reconstruction. MATERIALS AND METHODS: Forty-seven patients treated for ACL reconstruction using "over the top" technique were enrolled for this study. All patients received the same elastocompressive bandage. Regarding the coolant device, 23 patients were randomized to temperature-controlled continuous cold flow device (Hilotherm(r) group) and 24 patients were randomized to receive ice bag (control group). The two groups were homogenous for pre-operative (age, sex, and time "lesion to surgery") and intra-operative parameters (duration of the procedure, meniscectomy, and chondral damage). NRS (numeric rating scale), blood loss, knee volume increase at three established sites, ROM, and pain killers consumption were assessed. The subjective evaluation of the device including practicality and usefulness of the device was investigated. RESULTS: Hilotherm group resulted in lower pain perception (NRS), blood loss, knee volume increase at the patellar apex and 10 cm proximal to the superior patellar pole, and higher range of motion (p < 0.05) in the first post-operative day. No difference in pain killers consumption was noted. Hilotherm device was considered "comfortable" and "useful" by the majority of patients. CONCLUSIONS: Hilotherm group showed significant better results in first post-operative day. Further studies with higher number of patients and longer follow-up are required to assess the beneficial effects on rehabilitation and the cost-effectiveness of the routinely use of this device. LEVEL OF EVIDENCE: II. PMID- 26141536 TI - Rotational alignment of tibial components in mobile-bearing TKA: posterior substituted vs. PCL retaining. AB - PURPOSE: The medial border of the tibial tubercle (MBTT) is one of the fixed anatomic landmarks for tibial component setting during total knee arthroplasty (TKA). In mobile-bearing TKA using a tibial cut first technique, the final tibial component rotation can be guided by the position it achieves following several flexion-extension cycles. In this study, tibial component angle (TCA) and tibial rotational angle (TRA) were determined in dependence of retention or resection of the posterior cruciate ligament (PCL). METHODS: The TCA and TRA were examined in 206 patients who underwent primary TKA (PCL retaining: 104 knees, PCL substituting: 102 knees). The tibial component rotation was intraoperatively setting between the parallel to the axis of the most medial aspect of the tibial tubercle as the anterior anatomic landmark and the center of the tibial component as the posterior landmark at the maximum coverage with the osteotomized tibial plateau with its adjustment after several knee flexion-extension exercises. A postoperative quantitative three-dimensional computed tomography technique was used for measurements by a single observer. RESULTS: The TCA showed a divergence of 0.21 degrees external to the MBTT in the PCL-retaining design and 1.62 degrees internal divergence in the PCL-substituting design. The TRA showed an internal divergence of 0.88 degrees in the PCL-retaining design and an internal divergence of 2.12 degrees in the PCL-substituting design. There were no significant differences between the two designs. CONCLUSIONS: The MBTT might be regarded as a reliable landmark for obtaining an acceptable tibial rotational setting in mobile-bearing TKA despite PCL retention. PMID- 26141537 TI - Pelvic movement strategies and leg extension power in patients with end-stage medial compartment knee osteoarthritis: a cross-sectional study. AB - INTRODUCTION: During movement tasks, patients with medial compartment knee osteoarthritis use compensatory strategies to minimise the joint load of the affected leg. Movement strategies of the knees and trunk have been investigated, but less is known about movement strategies of the pelvis during advancing functional tasks, and how these strategies are associated with leg extension power. The aim of the study was to investigate pelvic movement strategies and leg extension power in patients with end-stage medial compartment knee osteoarthritis compared with controls. MATERIALS AND METHODS: 57 patients (mean age 65.6 years) scheduled for medial uni-compartmental knee arthroplasty, and 29 age and gender matched controls were included in this cross-sectional study. Leg extension power was tested with the Nottingham Leg Extension Power-Rig. Pelvic range of motion was derived from an inertia-based measurement unit placed over the sacrum bone during walking, stair climbing and stepping. RESULTS: Patients had lower leg extension power than controls (20-39 %, P < 0.01) and used greater pelvic range of motion during stair and step ascending and descending (P <= 0.03, except for pelvic range of motion in the frontal plane during ascending, P > 0.06). Furthermore, an inverse association (coefficient: -0.03 to -0.04; R (2) = 13-22 %) between leg extension power and pelvic range of motion during stair and step descending was found in the patients. CONCLUSIONS: Compared to controls, patients with medial compartment knee osteoarthritis use greater pelvic movements during advanced functional performance tests, particularly when these involve descending tasks. Further studies should investigate if it is possible to alter these movement strategies by an intervention aimed at increasing strength and power for the patients. PMID- 26141538 TI - Continuity of care from child and adolescent to adult mental health services: evidence from a regional survey in Northern Italy. AB - To examine clinical and demographic factors associated with continuity of care from child-adolescent (CAMHS) to adult mental health services (AMHS), we undertook a record-linkage study to the Adult Mental Health Information System including all those 16 years old and over who were listed between 2010 and 2013 in the Child and Adolescent Neuropsychiatry Information System in Emilia-Romagna, an Italian region of nearly 4.5 million residents. From a cohort of 8239 adolescents attending CAMHS (population at risk about 144,000), 821 (19.4 %) moved to AMHS, excluding cases with specific developmental disorders, whose conditions were not managed by adult psychiatrists, and those with mental retardation who attended usually social services. Young people referred for treatment to AMHS were more likely to receive a discharge diagnosis of schizophrenia and related disorders (Odds Ratio [OR] 3.92; 95 % confidence interval [CI] 2.17-7.08), personality disorders (OR 2.69; 95 % CI 1.89-3.83), and pervasive developmental disorders (OR 2.13; 95 % CI 1.51-2.99). Further factors predicting transfer to AMHS were not living with parents, inpatient psychiatric admission, and being on medication in the previous 24 months. These findings suggest that a relatively small number of adolescents moved to AMHS and are likely to reflect the configuration of local mental health services and alternative care available, mainly for those with less-severe mental disorders. PMID- 26141539 TI - Hyperparathyroidism and the general paediatrician. PMID- 26141540 TI - Spontaneous pneumothorax in children: the problem with rare presentations. PMID- 26141541 TI - Short stature and pubertal delay in Duchenne muscular dystrophy. AB - Children with Duchenne muscular dystrophy (DMD) are shorter than their healthy peers. The introduction of corticosteroid (CS) has beneficial effects on muscle function but slows growth further and is associated with pubertal delay. In contrast to CS usage in most children and adolescents, weaning glucocorticoid is not a key objective of management in DMD. As the outlook for these young people improves, one of the main challenges is to reduce or offset the detrimental effects of CS on growth and development. This is a review of the aetiology and prevalence of short stature and delayed puberty in DMD, a summary of the treatments available and suggestions for areas of further research. PMID- 26141542 TI - Effects of day-time exposure to different light intensities on light-induced melatonin suppression at night. AB - BACKGROUND: Bright nocturnal light has been known to suppress melatonin secretion. However, bright light exposure during the day-time might reduce light induced melatonin suppression (LIMS) at night. The effective proportion of day time light to night-time light is unclear; however, only a few studies on accurately controlling both day- and night-time conditions have been conducted. This study aims to evaluate the effect of different day-time light intensities on LIMS. METHODS: Twelve male subjects between the ages of 19 and 23 years (mean +/- S.D., 20.8 +/- 1.1) gave informed consent to participate in this study. They were exposed to various light conditions (<10, 100, 300, 900 and 2700 lx) between the hours of 09:00 and 12:00 (day-time light conditions). They were then exposed to bright light (300 lx) again between 01:00 and 02:30 (night-time light exposure). They provided saliva samples before (00:55) and after night-time light exposure (02:30). RESULTS: A one-tailed paired t test yielded significant decrements of melatonin concentration after night-time light exposure under day-time dim, 100- and 300-lx light conditions. No significant differences exist in melatonin concentration between pre- and post-night-time light exposure under day-time 900- and 2700-lx light conditions. CONCLUSIONS: Present findings suggest the amount of light exposure needed to prevent LIMS caused by ordinary nocturnal light in individuals who have a general life rhythm (sleep/wake schedule). These findings may be useful in implementing artificial light environments for humans in, for example, hospitals and underground shopping malls. PMID- 26141543 TI - Outcomes after aortic arch reconstruction for infants: deep hypothermic circulatory arrest versus moderate hypothermia with selective antegrade cerebral perfusion. AB - OBJECTIVES: Optimal cerebral and visceral protection is crucial in aortic arch surgery. The main method for this protection has traditionally been deep hypothermic circulatory arrest (DHCA). Recently, antegrade cerebral perfusion with moderate hypothermia has become the preferred strategy for adult patients and some children undergoing aortic arch surgery. Continuous cerebral perfusion should reduce the incidence of neurological complications, but the degree of damage to organs and systems resulting from the lack of blood flow distal to the aortic arch remains unclear. Here, we aimed to evaluate the efficacy and safety of methods of protecting the brain and internal organs during aortic arch surgery in infants. METHODS: We performed a retrospective review of 62 patients who underwent aortic arch reconstruction to assess their neurological status and internal injuries after different methods of cerebral protection. RESULTS: Surgical correction of aortic arch congenital abnormalities was performed under DHCA in 27 patients (Group I), and unilateral selective antegrade cerebral perfusion (SACP) was performed in 35 patients (Group II). In Group I, 30.8% of patients had neurological complications, whereas in Group II 5.9% had neurological complications. The odds ratio for a neurological event was significantly lower in Group II compared with Group I-0.14 [(95% CI 0.02-0.63), P = 0.02]. However, incidence of renal dysfunction was significantly higher in the second group than the first: 21 (61.2%) vs 5 (19.2%) cases, respectively [odds ratio 6.49 (95% CI 1.41-38.26), P = 0.02]. CONCLUSIONS: Aortic arch reconstruction accompanied by SACP has a lower risk of neurological complications compared with DHCA. However, the high incidence of renal complications with SACP requires further study. PMID- 26141544 TI - Quantitative real-time PCR (qPCR) for Eimeria tenella replication--Implications for experimental refinement and animal welfare. AB - The Eimeria species are highly pathogenic parasites of chickens. Research aimed at reducing their impact is hindered by a lack of non-subjective, quantitative, tools to measure parasite replication in the host. The time-consuming, and often time-sensitive, nature of existing approaches precludes their use in large-scale genetic, epidemiological, and evolutionary analyses. We have used quantitative real-time PCR (qPCR) to accurately quantify Eimeria tenella in chicken tissue and shown this to be more efficient and sensitive than traditional methodologies. We tested four chicken-specific reference qPCR assays and found beta-actin (actb) to be optimal for sample normalisation. In an experimental setting, chickens were inoculated with 500, 1500, or 4500 E. tenella oocysts and parasite replication and the impact of infection measured by i) qPCR analysis of DNA extracted from caecal tissues collected at five and eight days post-infection (dpi), ii) faecal oocyst counts (FOCs) on samples taken from six to eight dpi, and iii) lesion scoring on caeca collected post-mortem at five and eight dpi. Quantitative real time PCR test results indicated a significant dose-dependent increase in parasite numbers among study groups for samples collected five dpi (i.e., prior to gametogony) (R(2)=0.994) (p<0.002) but not in those from day eight (after most oocyst shedding) (R(2)=0.006) (p>0.379). A strong dose-dependent increase in parasite replication and severity of infection was also revealed by FOC (R(2)=0.997) and lesion scoring. Importantly, qPCR offers substantial improvements for animal welfare via improved statistical power and reduced group sizes in experimental studies. The described qPCR method overcomes subjective limitations of coproscopic quantification, allows reproducible medium- to high throughput examination of tissues, faeces, and oocysts, and is a valuable tool for determining the impact of Eimeria infections in both experimental and field settings. PMID- 26141545 TI - Evaluation of Acquired Valvular Heart Disease by the Pediatrician: When to Follow, When to Refer for Intervention? Part I. AB - Lesions of the heart valves are the commonest acquired cardiac abnormalities seen in pediatric age group. In India, the underlying cause for most valvular diseases is chronic rheumatic heart disease (RHD). The aim of evaluation of patients with valvular heart disease is not only to make a diagnosis, but also to decide the management plan. The pediatrician or physician is usually the first health care provider to whom such patients (or their parents) report. It is therefore imperative that the general physician and pediatricians are well versed with valvular heart diseases. Valvular abnormalities produce characteristic murmurs and a bedside diagnosis is possible in majority. However, further investigations such as X ray of the chest and an ECG are useful tools to refine the diagnosis. Echocardiography is now widely available to most of the patients in India and is very useful for assessing the severity of valve lesion and to identify the underlying etiology. Serial echocardiography is instrumental in deciding the timing of intervention. Mitral valve is most commonly affected followed by aortic; in some patients both valves may be affected. The valve may not close properly, resulting in regurgitation of blood flow in reverse direction or does not open fully (stenosis). In mitral regurgitation (MR), the blood flows in the reverse direction. MR can occur secondary to several causes, but in India, the commonest cause is RHD. Patient may remain asymptpmatic for a long period of time. Symptoms include fatigue, palpitations and later exertional breathlessness. MR typically produces a pansystolic murmur at apex, which may radiate to left axilla. Surgical intervention is reserved for all symptomatic patients with severe MR. Valve repair is preferred over prosthetic valve replacement. Mitral stenosis (MS) is almost always due to RHD. Severe MS results in pulmonary hypertension, right ventricular failure and tricuspid regurgitation. Patients are often symptomatic with dyspnea. Hemoptysis may occur. A typical rumbling mid diastolic murmur is the hallmark of MS. Balloon mitral valvotomy, performed in the catheterization lab, is recommended for severe MS. PMID- 26141546 TI - Acute Bronchiolitis: Still No New Treatments to Offer. PMID- 26141547 TI - Continuous Positive Airway Pressure: Method of Discontinuing in Neonates, Unresolved. PMID- 26141548 TI - Concurrent Intramedullary and Intracerebral Tuberculoma. PMID- 26141549 TI - Feasibility and Safety of Therapeutic Hypothermia and Short Term Outcome in Neonates with Hypoxic Ischemic Encephalopathy. AB - Therapeutic hypothermia is well known for neuroprotection in asphyxiated neonates with hypoxic ischemic encephalopathy. The authors aimed to study the feasibility and safety of therapeutic hypothermia and short term outcome in neonates with hypoxic ischemic encephalopathy (HIE). Total 31 neonates with moderate to severe HIE were enrolled in the study. Continuous temperature recording was noted in 31 neonates; 17 neonates were studied prospectively while 14 neonates were studied retrospectively. Rectal temperature was monitored in 31 neonates and maintained between 33 and 34 degrees C by switching off the warmer and using ice packs. Reusable ice packs were used which were inexpensive. Therapeutic hypothermia was maintained for 72 h and babies were then rewarmed 0.5 degrees C every hour. Therapeutic hypothermia was feasible and inexpensive. There was no major complication during the study. MRI was done in 17 neonates; 52 % were found to have normal MRI at the end of first week. Among the study neonates (n = 31) 64.5 % were neurologically normal at the time of discharge. To conclude, therapeutic hypothermia is feasible in a low resource setting and is a safe way of neuroprotection. Short term outcome was also favourable in these neonates. PMID- 26141550 TI - The regulation of cell therapy products in Canada. AB - This article provides a high level view of how cell therapy products are regulated in Canada and addresses the regulatory framework, pathways and underlying regulatory authority. The regulatory approach involves, primarily, two major sets of regulations; and the scientific basis for product categorization and the application of each of these pathways is discussed. Products that undergo more than minimal levels of processing, or meet certain other criteria, are regulated as biological drugs under the applicable parts of the Food and Drug Regulations. Other cellular products, primarily those for allogeneic transplantation and with an established therapeutic use, are regulated under the more recently promulgated Safety of Human Cells, Tissues and Organs for Transplantation Regulations, which incorporate a standards-based approach. Various concerns and challenges for these classes of products are discussed and information is provided on current sources of relevant guidance, including specific Health Canada guidance currently being developed. Health Canada strongly supports and participates in efforts aimed at international regulatory convergence and harmonization. PMID- 26141553 TI - Pregnancy adverse outcomes related to pregravid body mass index and gestational weight gain, according to the presence or not of gestational diabetes mellitus: A retrospective observational study. AB - AIM: This study retrospectively evaluated the complications associated with prepregnancy overweight (OW) or obesity (OB) and gestational weight gain (GWG) in women with or without universally screened and treated gestational diabetes mellitus (GDM). METHODS: A total of 15,551 non-Asian women without pregravid diabetes or hypertension who delivered singleton babies (2002-2010) were classified according to GDM (13.5%), pregestational body mass index (BMI; normal range: 18.5-24.9kg/m(2)), OW (26.2%), OB (13.9%; BMI>=30kg/m(2)) and GWG (<7kg: 32%; 7-11.5kg: 37%; 11.6-16kg: 23%;>16kg: 8%). Main outcome measures were large/small for gestational age (LGA/SGA), caesarean section, preeclampsia, preterm delivery and shoulder dystocia. RESULTS: GDM was associated with more LGA babies [Odds Ratio (OR): 2.12, 95% confidence interval (CI): 1.85-2.43], caesarean section (OR: 1.49, 95% CI: 1.34-1.65) and preeclampsia (OR: 1.59, 95% CI: 1.21-2.09). OW/OB and GWG were associated with LGA infants whatever the GDM status, and with SGA babies only in women without GDM. LGA status was independently associated with GWG in women with GDM (11.6-16kg: OR: 1.74, 95% CI: 1.49-2.03 and>16kg OR: 3.42, 95% CI: 2.83-4.13 vs 7-11.5kg) and in women without GDM (OR: 2.14, 95% CI: 1.54-2.97 or OR: 2.65, 95% CI: 1.68-4.17, respectively), and with BMI only in women without GDM (OR: 1.12, 95% CI: 1.00-1.24, per 10kg/m(2)). SGA status was independently associated with OW (OR: 0.86, 95% CI: 0.77-0.98), OB (OR: 0.84, 95% CI: 0.72-0.98) and GWG<7kg (1.14, 95% CI: 1.01 1.29) only in women without GDM. CONCLUSION: In our European cohort and considering the triumvirate of GDM, BMI and GWG, GDM was the main contributor to caesarean section and preeclampsia. OW/OB and GWG contributed to LGA and SGA infants mainly in women without GDM. PMID- 26141551 TI - Patient- and Community-Level Sociodemographic Characteristics Associated with Emergency Department Visits for Childhood Injury. AB - OBJECTIVE: To examine pediatric emergency department (ED) visits over 5 years, trends in injury severity, and associations between injury-related ED visit outcome and patient and community-level sociodemographic characteristics. STUDY DESIGN: Retrospective analysis of administrative data provided to the Pediatric Emergency Care Applied Research Network Core Data Project, 2004-2008. Home addresses were geocoded to determine census block group and associated sociodemographic characteristics. Maximum Abbreviated Injury Scale severity and Severity Classification System scores were calculated. Generalized estimating equations were used to test for associations between sociodemographic characteristics and admission or transfer among injury-related ED visits. RESULTS: Overall ED visits and injury-related visits increased from 2004 to 2008 at study sites. Of 2,833676 successfully geocoded visits, 700,821 (24.7%) were injury-related. The proportion of higher severity injury-related visits remained consistent. Nearly 10% of injury-related visits resulted in admission or transfer each year. After adjusting for age, sex, payer, and injury severity, odds of admission or transfer were lower among minority children and children from areas with moderate and high prevalence of poverty. CONCLUSIONS: Pediatric injury related ED visits to included sites increased over the study period while injury severity, anticipated resource utilization, and visit outcomes remained stable, with low rates of admission or transfer. Sociodemographic differences in injury related visits and ED disposition were apparent. ED-based injury surveillance is essential to understand disparities, inform targets for prevention programs, and reduce the overall burden of childhood injuries. PMID- 26141552 TI - Serum Cardiac Troponin I in the Evaluation of Nonaccidental Trauma. AB - OBJECTIVE: To determine if troponin I is more often elevated in children with suspected nonaccidental trauma (NAT) compared with uninjured children of similar age, and describe associations between troponin I elevation and NAT injuries. STUDY DESIGN: Prospective 2-group study of children less than 2 years of age presenting to the emergency department with nonaccidental abdominal, thoracic, or intracranial injuries, and similarly aged uninjured children. Primary outcome was serum troponin I (>= 0.04 ng/mL) using frozen blood samples from the 2 groups. Secondary outcomes included descriptive analyses of age, injury characteristics, and clinical appearance. RESULTS: There were 129 subjects; 60 injured patients and 69 uninjured patients. Groups had similar age and sex. Troponin I was elevated in 38% of injured children compared with 17% of uninjured children (P = .008). No uninjured patient over 3 months of age had elevated troponin I. Abdominal trauma, acute rib fractures, or the child's ill-appearance in the emergency department were associated with having elevated troponin I. CONCLUSIONS: Troponin I is more often elevated in children with suspected NAT than uninjured children. Elevation of troponin I in children greater than 3 months of age with suspected NAT is concerning for trauma. Occult cardiac injury is more likely to occur in children with inflicted abdominal trauma, acute rib fractures, or ill appearance. PMID- 26141555 TI - Total mesorectal excision for rectal cancer with emphasis on pelvic autonomic nerve preservation: Expert technical tips for robotic surgery. AB - The primary goal of surgical intervention for rectal cancer is to achieve an oncologic cure while preserving function. Since the introduction of total mesorectal excision (TME), the oncologic outcome has improved greatly in terms of local recurrence and cancer-specific survival. However, there are still concerns regarding functional outcomes such as sexual and urinary dysfunction, even among experienced colorectal surgeons. Intraoperative nerve damage is the primary reason for sexual and urinary dysfunction and occurs due to lack of anatomical knowledge and poor visualization of the pelvic autonomic nerves. The rectum is located concavely along the curved sacrum and both the ischial tuberosity and iliac wing limit the pelvic cavity boundary. Thus, pelvic autonomic nerve preservation during dissection in a narrow or deep pelvis, with adherence to the TME principles, is very challenging for colorectal surgeons. Recent developments in robotic technology enable overcoming these difficulties caused by complex pelvic anatomy. This system can facilitate better preservation of the pelvic autonomic nerve and thereby achieve favorable postoperative sexual and voiding functions after rectal cancer surgery. The nerve-preserving TME technique includes identification and preservation of the superior hypogastric plexus nerve, bilateral hypogastric nerves, pelvic plexus, and neurovascular bundles. Standardized procedures should be performed sequentially as follows: posterior dissection, deep posterior dissection, anterior dissection, posterolateral dissection, and final circumferential pelvic dissection toward the pelvic floor. In future perspective, a structured education program on nerve-preserving robotic TME should be incorporated in the training for minimally invasive surgery. PMID- 26141554 TI - In situ H(+)-mediated formation of singlet oxygen from NaBiO3 for oxidative degradation of bisphenol A without light irradiation: Efficiency, kinetics, and mechanism. AB - Bisphenol A (BPA) is a ubiquitous environmental contaminant with endocrine disruption potential. This study explored the efficiency, kinetics, and mechanism of BPA removal from weakly acidic solutions by using NaBiO3 as a source of singlet oxygen. It was observed that the use of NaBiO3 (1gL(-1)) could eliminate almost all (more than 97%) of the added BPA (0.1mmolL(-1)) in solutions at pH 5.0 in 60min. The degradation of BPA followed pseudo-first-order kinetics over the pH range from 3 to 9, and the pseudo-first-order rate constant (k) was dependent on pH, NaBiO3 concentration and the coexisting compounds. As solution pH was decreased from 9 to 3 or NaBiO3 concentration was increased from 0.5 to 2gL(-1), the k value was increased logarithmically. Humic acid and Fe(3+) showed little effect on the BPA removal, but Mn(2+) exhibited exceptionally enhancing effect on the degradation of BPA. The involved reactive species were identified as singlet oxygen by using radical scavenger probes and ESR measurement, and the generated singlet oxygen was confirmed to be generated from the decomposition of NaBiO3 mediated by H(+) ions. PMID- 26141557 TI - Editorial Introduction. PMID- 26141556 TI - Peritoneal carcinomatosis: A malignant disease with an embryological origin? AB - INTRODUCTION: In 1931, Simpson et al. coined the term "peritoneal carcinomatosis" to describe the regional spread of ovarian tumors as localized or extended with involvement of the peritoneal serous membrane and neighboring anatomical structures. Research into the origin of peritoneal carcinomatosis is based on two phases in a woman's life: EMBRYO DEVELOPMENT: During week 3, the bilaminar disc becomes a trilaminar disc called the mesoderm. Inside the lateral plate mesoderm, the coelomic cavity is divided into 2 layers: the parietal (somatic) mesoderm, which gives rise to the parietal peritoneum and pleural surfaces; and the visceral (splanchnic) mesoderm, which gives rise to the visceral peritoneum, visceral surface of the pleura, gonadal stroma, and the muscular layer of the hollow viscera and its mesenteries. TUMOR SPREAD: Transcoelomic metastasis and metaplasia of pluripotent stem cells in the peritoneum was involved in the pathogenesis of ovarian cancer. This involvement takes the form of a synchronous malignant transformation at multiple foci and may cause intraperitoneal field cancerization. Pluripotent stem cells play a role both in the development of the embryonic peritoneum and in the spread of transcoelomic tumors. Consequently, knowledge of the origin of these cells (embryonic or current) could be extremely useful. The many markers that act during the embryonic period can affect descendants, that is, cells are already marked before specification and differentiation are activated. Thus, programmed activation could be attributed to genetic and epigenetic changes. PMID- 26141558 TI - The Inner World of the Genetic Counselor. AB - The external experience of genetic counselors reflects and is processed in their personal inner worlds. A small window into that private interior is opened here revealing the strengths and frailties, vulnerabilities and sensitivities professionals bring to bear in their work. The relational, human interplay between counselor and colleagues, counselor and clients, counselors in their nonprofessional roles relative to others-is the primary focus of the interior experience. PMID- 26141559 TI - Commentary on The Inner World of the Genetic Counselor: The Unexamined Counseling Life. PMID- 26141560 TI - A Qualitative Investigation of Student and Supervisor Perceptions of Live Supervision in Genetic Counseling. AB - Live supervision of genetic counseling students is critical for ensuring quality client care and student clinical skill development. However, no research has investigated students' and supervisors' experience of this primary supervision method. In this study, separate focus groups of students and supervisors discussed their perceptions of the nature and impact of live supervision. A modified Consensual Qualitative Research method (Hill et al. (1997) Couns Psychol 25:517-572) was used to analyze the data. Results suggest that live supervision is an essential and effective method that promotes student skill development and professional development for both students and supervisors. There is a lack of formal training regarding supervision; most learning is trial and error. Students worry about being evaluated, and supervisors wonder if they are providing supervision effectively. Both samples emphasized that client care should not be compromised. Participant recommendations for improving live supervision are described, and suggestions are made for future research. PMID- 26141561 TI - Incorporating a Psychological Counselor in a Cancer Risk Assessment Program: Necessity, Acceptability, and Potential Roles. AB - Evidence suggests that cancer risk assessment may be associated with increased psychological distress. This exploratory study assessed the necessity and acceptability of incorporating psychological counseling into routine clinic procedures at a cancer risk program. Following a visit to a university-based cancer risk clinic, patients (N = 102) completed an anonymous self-report instrument. Participants reported experiencing current stress and anxiety (41%), depression (29%), and suicidal ideation (2%). Patients with a history of cancer were more likely to be experiencing current emotional difficulties. Sixty-nine percent of the participants found the visit with the psychological counselor to be helpful, while 41% of the participants reported interest in follow-up psychological services. Interest in receiving future psychological services was positively correlated with levels of anxiety, depression, and cancer worry. This pilot study demonstrates the acceptability and potential role for psychological counselors in increasing adjustment in high-risk patients undergoing genetic counseling for inherited cancers. PMID- 26141562 TI - Letter to the Editor: Insurance Justification Letters. PMID- 26141563 TI - Errata. PMID- 26141564 TI - The effect of spatial barriers on realised accessibility to heath services after a natural disaster. AB - The closure of the Manawatu Gorge in New Zealand in August 2011 caused a change in the travel time for patients living in the east of the MidCentral Health District to their health services located in Palmerston North. This presented an opportunity to study the effect a change in spatial access had on a population before and after such an event. We used a retrospective cohort design with routinely collected data from general practice and hospital services. Realised accessibility was calculated for 101,456 patients over 3.5 years. General practice utilization appeared to be the only service affected negatively during the gorge closure (rate ratio 1.106). Outpatient attendances had an increase in use by those with increased travel time (rate ratio 0.922). There was evidence of other unidentified factors that impacted the use of services across both intervention and control groups between the gorge open and closed periods. These results were more conservative than those produced by a traditional uncontrolled travel time category analysis which suggested a correlation in non-urgent ED attendance and general practice and boundary effects in all ED attendances and hospital admissions. PMID- 26141565 TI - Making unhealthy places: The built environment and non-communicable diseases in Khayelitsha, Cape Town. AB - In this paper, we examine how economic, social and political forces impact on NCDs in Khayelitsha (a predominantly low income area in Cape Town, South Africa) through their shaping of the built environment. The paper draws on literature reviews and ethnographic fieldwork undertaken in Khayelitsha. The three main pathways through which the built environment of the area impacts on NCDs are through a complex food environment in which it is difficult to achieve food security, an environment that is not conducive to safe physical activity, and high levels of depression and stress (linked to, amongst other factors, poverty, crime and fear of crime). All of these factors are at least partially linked to the isolated, segregated and monofunctional nature of Khayelitsha. The paper highlights that in order to effectively address urban health challenges, we need to understand how economic, social and political forces impact on NCDs through the way they shape built environments. PMID- 26141566 TI - Genetic analysis of durable resistance to Magnaporthe oryzae in the rice accession Gigante Vercelli identified two blast resistance loci. AB - Rice cultivars exhibiting durable resistance to blast, the most important rice fungal disease provoking up to 30 % of rice losses, are very rare and searching for sources of such a resistance represents a priority for rice-breeding programs. To this aim we analyzed Gigante Vercelli (GV) and Vialone Nano (VN), two temperate japonica rice cultivars in Italy displaying contrasting response to blast, with GV showing a durable and broad-spectrum resistance, whereas VN being highly susceptible. An SSR-based genetic map developed using a GV * VN population segregating for blast resistance identified two blast resistance loci, localized to the long arm of chromosomes 1 and 4 explaining more than 78 % of the observed phenotypic variation for blast resistance. The pyramiding of two blast resistance QTLs was therefore involved in the observed durable resistance in GV. Mapping data were integrated with information obtained from RNA-seq expression profiling of all classes of resistance protein genes (resistance gene analogs, RGAs) and with the map position of known cloned or mapped blast resistance genes to search candidates for the GV resistant response. A co-localization of RGAs with the LOD peak or the marker interval of the chromosome 1 QTL was highlighted and a valuable tool for selecting the resistance gene during breeding programs was developed. Comparative analysis with known blast resistance genes revealed co positional relationships between the chromosome 1 QTL with the Pi35/Pish blast resistance alleles and showed that the chromosome 4 QTL represents a newly identified blast resistance gene. The present genetic analysis has therefore allowed the identification of two blast resistance loci in the durable blast resistant rice cultivar GV and tools for molecular selection of these resistance genes. PMID- 26141567 TI - Retention of functional genes for S19 ribosomal protein in both the mitochondrion and nucleus for over 60 million years. AB - Ribosomal protein genes occasionally undergo successful migration from the mitochondrion to the nucleus in flowering plants and we previously presented evidence that the S19 ribosomal protein gene (rps19) had been transferred to the nucleus in the common ancestor of Poaceae grasses. In many lineages, the mitochondrial copy was subsequently lost or pseudogenized, although in rice it was retained and the nuclear copy lost. We have now determined that functional rps19 genes are present in both the mitochondrion and nucleus in brome grass (Bromus inermis). The mitochondrion-located rps19 gene, which is immediately downstream of an rpl2 pseudogene, is transcribed and edited. The nuclear-located rps19 gene is also actively expressed and it possesses the same intron-containing hsp70-type presequence as its counterparts in other grasses, as well as shared derived amino acids within the S19 core. We conclude that this brome rps19 gene is derived from the same transfer event that occurred in the common ancestor of grasses at least 60 million years ago. In the oat lineage, a subsequent exon shuffling-type event has resulted in novel amino-terminal sequences replacing part of the hsp70 presequence, and in the barley lineage, there has been an additional DNA-mediated transfer of the mitochondrial rps19 gene and its flanking sequences, followed by relatively recent loss of the mitochondrion-located copy. The prolonged persistence of functional copies in both compartments, as evidenced by present-day brome, raises interesting questions about their respective roles. PMID- 26141569 TI - Antimicrobial treatment of bacterial infections in frail elderly patients: the difficult balance between efficacy, safety and tolerability. AB - The elderly population is increasing worldwide and shows an increasing prevalence of frailty. Frailty is recognized as an important factor for inappropriate drug prescribing in elderly patients. Appropriate drug prescription, either in terms of drug choice or in terms of drug dosage, is of paramount importance among the frail elderly patients, this requiring the need of a difficult balance between efficacy, safety and tolerability. Bacterial infections are quite frequent among the elderly, and use of antimicrobials may be associated with severe adverse events in this population, especially when in presence of co-medications and/or of co-morbidities. The aim of this paper is to argue about the most recent published evidences on how to prevent major adverse events whenever antimicrobials should be co-prescribed in frail elderly patients. PMID- 26141570 TI - [Otorrhagia. A complication of laparoscopic hemicolectomy]. AB - The fast and increasing advance in surgical technology during the last decades has led to a remarkable development in laparoscopic surgery. "Minimally invasive" surgery has become very popular in the last few years, not only in gynecological procedures but also in general surgery, orthopedics, thoracic and urological procedures. Gas inflation into the abdominal cavity and patient position provokes physiological changes, as well as complications that are not seen in open surgery. Pneumoperitoneum and the Trendelenburg position beyond 35 degrees cause hemodynamic changes, resulting in an increase in arterial and central venous pressure. The external auditory canal vessels are directly affected by these changes, and postoperative otorrhagia after a prolonged laparoscopic surgery may be present. A case is presented of postoperative bilateral otorrhagia after laparoscopic left hemicolectomy. PMID- 26141568 TI - Redoxal, an inhibitor of de novo pyrimidine biosynthesis, augments APOBEC3G antiviral activity against human immunodeficiency virus type 1. AB - APOBEC3G (A3G) is a cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA; deamination-independent mechanisms are also implicated. HIV-1 Vif protein counteracts A3G by inducing its proteasomal degradation. Thus, the Vif-A3G axis is a potential therapeutic target. To identify compounds that inhibit Vif:A3G interaction, a 307,520 compound library was tested in a TR-FRET screen. Two identified compounds, redoxal and lomofungin, inhibited HIV-1 replication in peripheral blood mononuclear cells. Lomofungin activity was linked to A3G, but not pursued further due to cytotoxicity. Redoxal displayed A3G-dependent restriction, inhibiting viral replication by stabilizing A3G protein levels and increasing A3G in virions. A3G-independent activity was also detected. Treatment with uridine or orotate, intermediates of pyrimidine synthesis, diminished redoxal-induced stabilization of A3G and antiviral activity. These results identify redoxal as an inhibitor of HIV-1 replication and suggest its ability to inhibit pyrimidine biosynthesis suppresses viral replication by augmenting A3G antiviral activity. PMID- 26141572 TI - Continuous distending pressure for respiratory distress in preterm infants. AB - BACKGROUND: Respiratory distress syndrome (RDS) is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory insufficiency, intermittent positive pressure ventilation (IPPV) with surfactant is the standard treatment for the condition, but it is invasive, potentially resulting in airway and lung injury. Continuous distending pressure (CDP) has been used for the prevention and treatment of RDS, as well as for the prevention of apnoea, and in weaning from IPPV. Its use in the treatment of RDS might reduce the need for IPPV and its sequelae. OBJECTIVES: To determine the effect of continuous distending pressure (CDP) on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress.Subgroup analyses were planned on the basis of birth weight (> or < 1000 or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), methods of application of CDP (i.e. CPAP and CNP), application early versus late in the course of respiratory distress and high versus low pressure CDP and application of CDP in tertiary compared with non-tertiary hospitals, with the need for sensitivity analysis determined by trial quality.At the 2008 update, the objectives were modified to include preterm infants with respiratory failure. SEARCH METHODS: We used the standard search strategy of the Neonatal Review Group. This included searches of the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, 2015 Issue 4), MEDLINE (1966 to 30 April 2015) and EMBASE (1980 to 30 April 2015) with no language restriction, as well as controlled-trials.com, clinicaltrials.gov and the International Clinical Trials Registry Platform of the World Health Organization (WHO). SELECTION CRITERIA: All random or quasi-random trials of preterm infants with respiratory distress were eligible. Interventions were continuous distending pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharyngeal tube or endotracheal tube, or continuous negative pressure (CNP) via a chamber enclosing the thorax and the lower body, compared with spontaneous breathing with oxygen added as necessary. DATA COLLECTION AND ANALYSIS: We used standard methods of The Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each review author. MAIN RESULTS: We included six studies involving 355 infants - two using face mask CPAP, two CNP, one nasal CPAP and one both CNP (for less ill babies) and endotracheal CPAP (for sicker babies). For this update, we included no new trials.Continuous distending pressure (CDP) is associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.65, 95% confidence interval (CI) 0.52 to 0.81; typical risk difference (RD) -0.20, 95% CI -0.29 to -0.10; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 10; six studies; 355 infants), lower overall mortality (typical RR 0.52, 95% CI 0.32 to 0.87; typical RD -0.15, 95% CI -0.26 to -0.04; NNTB 7, 95% CI 4 to 25; six studies; 355 infants) and lower mortality in infants with birth weight above 1500 g (typical RR 0.24, 95% CI 0.07 to 0.84; typical RD -0.28, 95% CI -0.48 to -0.08; NNTB 4, 95% CI 2.00 to 13.00; two studies; 60 infants). Use of CDP is associated with increased risk of pneumothorax (typical RR 2.64, 95% CI 1.39 to 5.04; typical RD 0.10, 95% CI 0.04 to 0.17; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 17.00 to 25.00; six studies; 355 infants). We found no difference in bronchopulmonary dysplasia (BPD), defined as oxygen dependency at 28 days (three studies, 260 infants), as well as no difference in outcome at nine to 14 years (one study, 37 infants). AUTHORS' CONCLUSIONS: In preterm infants with respiratory distress, the application of CDP as CPAP or CNP is associated with reduced respiratory failure and mortality and an increased rate of pneumothorax. Four out of six of these trials were done in the 1970s. Therefore, the applicability of these results to current practice is difficult to assess. Further research is required to determine the best mode of administration. PMID- 26141571 TI - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AB - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. This review focuses on the clinical and immunological features of APECED, summarizes the current knowledge on the function of AIRE and discusses the importance of autoantibodies in disease diagnosis and prognosis. Additionally, we review the outcome of recent immunomodulatory treatments in APECED patients. PMID- 26141573 TI - Asthma is Different in Women. AB - Gender differences in asthma incidence, prevalence and severity have been reported worldwide. After puberty, asthma becomes more prevalent and severe in women, and is highest in women with early menarche or with multiple gestations, suggesting a role for sex hormones in asthma genesis. However, the impact of sex hormones on the pathophysiology of asthma is confounded by and difficult to differentiate from age, obesity, atopy, and other gender associated environmental exposures. There are also gender discrepancies in the perception of asthma symptoms. Understanding gender differences in asthma is important to provide effective education and personalized management plans for asthmatics across the lifecourse. PMID- 26141574 TI - The Complex Type 2 Endotype in Allergy and Asthma: From Laboratory to Bedside. AB - Better management of allergic diseases needs a sharpened understanding of disease heterogeneity and mechanisms in relation to clinically significant outcomes. Phenotypes describing observable clinical and morphologic characteristics and unique responses to treatment have been developed; however, they do not relate to disease mechanisms. Recently, extended heterogeneous and disease-related metabolic, inflammatory, immunological, and remodeling pathways have been described, and reproducible patterns are defined as disease endotypes. An endotype might consist of several intricated mechanisms that cannot be clearly separated into "pure single molecular mechanism" thus being a "complex endotype." The description of an endotype may rely on biomarkers, which can be the signature of a complex underlying pathway or a key molecule associated with or directly playing a role in a particular disease endotype. The Th2 type inflammation can be defined as a complex endotype in asthma and linked to mechanisms of disease development and response to treatment and to disease outcomes such as exacerbations and remodeling. The type 2 complex endotype in allergies and asthma includes innate lymphoid cells, T helper 2 cells, tissue eosinophilia, and IgE production. Currently, emerging endotype-driven strategies in asthma, particularly the development of biologicals that target a single molecular pathway, are being focused for solving individualized clinical problems on disease outcomes. Progress is also being made for endotyping rhinitis, chronic rhinosinusitis, and atopic dermatitis. PMID- 26141575 TI - IgG4-Related Ophthalmic Disease: Pooling of Published Cases and Literature Review. AB - In recent years, IgG4-related ophthalmic disease (IgG4-ROD) has emerged as a common cause of orbital inflammation, accounting for a substantial proportion of idiopathic orbital inflammation and lymphoid hyperplasia. The last pooled analysis of published cases was conducted in 2012, but a large number of new cases have been added to the literature since then. In this review, we present the demographic, clinical, histological, and treatment data for 172 published cases of biopsy-confirmed IgG4-ROD. Results are accompanied by a review of the relevant literature. PMID- 26141576 TI - Remodeling and Repair in Rhinosinusitis. AB - Remodeling refers to the development of specific but potentially irreversible structural changes in tissue. Caucasian eosinophilic chronic rhinosinusitis (CRS) with polyps associated or not with cystic fibrosis was discriminated by edema from CRS without nasal polyps, characterized by extensive fibrotic fields. However, changes in epithelial and extracellular matrix structures are common findings in all types of chronic inflammatory diseases of upper airways, but rarely specific and highly variable in extend. Recent studies have shown that remodeling in CRS appears to occur in parallel, rather than purely subsequent to inflammation. Furthermore, some preferential remodeling associations can be recognized. Tremendous efforts have been put in research on coagulation factors, cytokines, growth factors, and proteases supporting all phases of upper airway remodeling. The current exploration of other CRS sub-groups and of the particular link with concomitant asthma aims to optimize the classification of CRS and its staging modes and to develop novel therapies. PMID- 26141577 TI - The Other Itch That Rashes: a Clinical and Therapeutic Approach to Pruritus and Skin Picking Disorders. AB - Patients with skin picking disorders (SPDs) have historically been an under recognized and under treated group. Originally classified an impulse control disorder, skin picking disorder is now considered under the obsessive-compulsive disorder (OCD) and obsessive-compulsive-related disorder (OCRD) spectrum. Workup of SPD concentrates on differentiating this condition from primary skin disorders, systemic conditions associated with pruritus, and psychocutaneous syndromes. It is important to first address any underlying pruritic disorders (if present) that may be a trigger to pick the skin. First-line treatment for SPD is cognitive behavioral therapy. When necessary, pharmacologic therapy can be helpful as well. PMID- 26141578 TI - Review of Environmental Impact on the Epigenetic Regulation of Atopic Diseases. AB - There has been significant increase in the prevalence of atopy over the past decade that cannot be explained by genetic predisposition. Environmental factors including nutrition, the uterine environment, and lifestyle factors are known to play a role in gene expression through epigenetic modifications. In this article, we review the literature on the environmental impact on epigenetic modulation of atopic diseases including asthma, food allergy, eczema, and allergic rhinitis. Recent public release of epigenomic data for hundreds of human tissues provides a powerful resource for further investigation of the molecular basis of atopic diseases. PMID- 26141579 TI - Utility of Component-Resolved Diagnostics in Food Allergy. AB - Allergen component-resolved diagnostic testing (CRD) is a new methodology in clinical food allergy diagnosis, improving the ability to identify specific clinical phenotypes. Instead of relying on the crude allergen extracts used in standard allergy diagnostics, CRD utilizes purified or recombinant allergens for identification of specific molecules causing sensitization or allergy. This method is able to determine risk of the severity of allergic reactions in specific cases, like soy, peanut, and hazelnut allergy. The severity of allergic reaction can be predicted in peanut allergy with Ara h 2, and clinically relevant disease in pollen-allergic patients can be identified. However, age and geographic differences affect CRD results and it should always be utilized in the context of a clinical history. In the future, clinical phenotypes may be differentiated with larger prospective studies utilizing food challenges. PMID- 26141580 TI - Urticaria Guidelines: Consensus and Controversies in the European and American Guidelines. AB - Urticaria can present acutely and be self-limiting or become chronic and persist for weeks, months, or years. In either case, the condition may have a significant impact on the patient's quality of life. Two major consensus groups, the EAACI/WAO and the AAAAI/ACAAI Joint Task Force, have written guidelines on the diagnosis and management of urticaria. While both agree on most points regarding the definition, general evaluation, and treatment, there are some differences which exist. The guidelines, which are written to assist both primary practitioners and specialists in managing their patients with urticaria, have been developed based on scientific evidence, and when insufficient evidence is available, then recommendations are based on expert consensus opinion. The majority of the differences between the two guidelines pertain to recommendations based on expert opinion because of weak scientific evidence. Within this document, we compare the recommendations of these two groups, highlighting the key similarities and differences. PMID- 26141581 TI - An Examination of Clinical and Immunologic Outcomes in Food Allergen Immunotherapy by Route of Administration. AB - Allergen immunotherapy for the treatment of food allergy has been a subject of intensive study within the last 10 years. After an unsuccessful attempt with subcutaneous immunotherapy for peanut allergy, other routes with varying degrees of safety and efficacy have been tested for peanut, milk, and egg allergies. In this review, we summarize the results to date with oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy for the treatment of food allergy. While results of immunotherapy trials are promising, increases in efficacy are commonly associated with an increased side effect profile. There is a need for additional research beginning at the preclinical level to develop safe and effective treatments for food allergy. PMID- 26141582 TI - Smad2 and Smad3 Inversely Regulate TGF-beta Autoinduction in Clostridium butyricum-Activated Dendritic Cells. AB - Colonization with a mixture of Clostridium species has been shown to induce accumulation of induced regulatory T (iTreg) cells in the colon. Transforming growth factor-beta (TGF-beta) is an essential factor for iTreg cell induction; however, the relationship between Clostridium species and TGF-beta remains to be clarified. Here we demonstrated that a gram-positive probiotic bacterial strain, Clostridium butyricum (C. butyricum), promoted iTreg cell generation in the intestine through induction of TGF-beta1 from lamina propria dendritic cells (LPDCs). C. butyricum-mediated TGF-beta1 induction was mainly Toll-like receptor 2 (TLR2) dependent, and the ERK-AP-1 kinase pathway played an important role. In addition, the autocrine TGF-beta-Smad3 transcription factor signal was necessary for robust TGF-beta expression in DCs, whereas Smad2 negatively regulated TGF beta expression. Smad2-deficient DCs expressed higher concentrations of TGF-beta and were tolerogenic for colitis models. This study reveals a novel mechanism of TGF-beta induction by Clostridia through a cooperation between TLR2-AP-1 and TGF beta-Smad signaling pathways. PMID- 26141583 TI - Retinoic Acid Differentially Regulates the Migration of Innate Lymphoid Cell Subsets to the Gut. AB - Distinct groups of innate lymphoid cells (ILCs) such as ILC1, ILC2, and ILC3 populate the intestine, but how these ILCs develop tissue tropism for this organ is unclear. We report that prior to migration to the intestine ILCs first undergo a "switch" in their expression of homing receptors from lymphoid to gut homing receptors. This process is regulated by mucosal dendritic cells and the gut specific tissue factor retinoic acid (RA). This change in homing receptors is required for long-term population and effector function of ILCs in the intestine. Only ILC1 and ILC3, but not ILC2, undergo the RA-dependent homing receptor switch in gut-associated lymphoid tissues. In contrast, ILC2 acquire gut homing receptors in a largely RA-independent manner during their development in the bone marrow and can migrate directly to the intestine. Thus, distinct programs regulate the migration of ILC subsets to the intestine for regulation of innate immunity. PMID- 26141584 TI - Effect of gamma radiation on the growth, survival, hematology and histological parameters of rainbow trout (Oncorhynchus mykiss) larvae. AB - Effects of low (1, 2.5 and 5Gy) and high doses (10, 20 and 40Gy) of gamma radiation were examined on the growth, survival, blood parameters and morphological changes of the intestines of rainbow trout (Oncorhynchus mykiss) larvae (103+/-20mg) after 12 weeks of exposure. Negative effects of gamma radiation on growth and survival were observed as radiation level and time increased. Changes were well documented at 10 and 20Gy. All the fish were dead at the dose of 40Gy. In all the treatments, levels of red blood cells (RBC), hematocrit (HCT) and hemoglobin (HB) were significantly (P<0.05) declined as the irradiation levels increased, whereas the amount of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) did not change. No significant differences (P>0.05) were found in the levels of white blood cells (WBC), lymphocytes and monocytes. Destruction of the intestinal epithelium cells was indicated as the irradiation levels increased to 1Gy and above. The highest levels of growth, survival, specific growth rate (SGR), condition factor (CF) and protein efficiency rate (PER) were obtained in the control treatment. The results showed that gamma rays can be a potential means for damaging rainbow trout cells. PMID- 26141586 TI - Introduction. PMID- 26141585 TI - The effects of model androgen 5alpha-dihydrotestosterone on mummichog (Fundulus heteroclitus) reproduction under different salinities. AB - Endocrine disrupting substances (EDSs) have the potential to disturb sensitive hormone pathways, particularly those involved in development and reproduction. Both fresh and estuarine water bodies receive inputs of EDSs from a variety of sources, including sewage effluent, industrial effluent and agricultural runoff. Based on current literature, freshwater species appear to respond to lower levels of EDSs than estuarine or marine species. Therefore, effects elicited by EDSs in freshwater teleosts may not be an accurate representation of how EDSs affect teleosts in estuarine and marine environments. To address this potential difference, a short-term reproductive bioassay was conducted under conditions of low and high salinity using mummichog (Fundulus heteroclitus), a euryhaline species that is native to the east coast of North America. The goals of this study were to determine the response of mummichog when exposed to an androgenic EDS and whether salinity affected the response. A model androgen, 5alpha dihydrotestosterone (DHT), was selected for this experiment. Impacts on reproduction were evaluated at multiple biological levels, including physiological (sex steroid levels), organismal (gonad size and gonad morphology), and functional (egg production) endpoints. Under conditions of high salinity, egg production was significantly reduced at all exposure concentrations. Under conditions of low salinity, there were no significant differences based on DHT treatment; however, egg production in all treatment groups including the control were significantly reduced relative to the high salinity control group. Other reproductive endpoints, such as sex steroid production, showed stronger correlation to fecundity in females than males. This study demonstrates that mummichog fecundity is sensitive to androgenic endocrine disruption while also underscoring the importance of how changes in salinity, an environmental variable, can impact reproduction. PMID- 26141587 TI - Supervision for Practicing Genetic Counselors: An Overview of Models. AB - Supervision has traditionally been a concept that refers primarilyto a means by which to train genetic counseling students. However, supervision-redefined-can afford anextraordinary opportunity for practicing genetic counselors to regularly update and enhancetheir counseling skills. This paper provides a new definition of supervision for experiencedgenetic counselors and discusses the process and advantages of different types ofsupervision. The leader-led peer supervision group will be highlighted as especiallyamenable to the needs of genetic counselors for a collegial forum in which to discuss thepsychosocial components of their work. Immediately following, in a separate paper, will bea description of a currently ongoing supervision group for practicing genetic counselors. PMID- 26141588 TI - A Leader-Led Supervision Group as a Model for Practicing Genetic Counselors. AB - With the stage set by the overview of supervision models in the previous paper, thispaper now presents the development and evolution of a currently ongoing leader-ledsupervision group for experienced genetic counselors. I discuss the procedures forgetting started; the creation and maintenance of the contract; typical issues and themesconsidered; the format for case presentation; and the overall growth of the group and itsmembers. PMID- 26141589 TI - The Experience of Leader-Led Peer Supervision: Genetic Counselors' Perspectives. AB - As we proceed through our professional lives, it is essential that we challengeourselves in order to continue to develop our genetic counseling skills. Conferences, workshops,post-graduate courses, journal clubs, and involvement in professional organizations havebecome the traditional methods of continuing education for post-graduate geneticcounselors. While these forums address the need to stay updated on scientific orinformation-based topics, there is little available to counselors to promote growth incounseling skills. A group of Boston based genetic counselors describe how their leader-ledsupervision group has established a setting to meet the needs of its members both forsupport and continued counseling training. We outline here the evolution of this group andhow it has become a valued part of our professional lives. We feel that the model of leader-ledpeer supervision holds great value in helping genetic counselors continue to enhancetheir interpersonal skills in a supportive, safe, and challenging environment. It is our hopethat others will elect to form similar groups in their own communities, thereby creating newopportunities for growth within the genetic counseling profession. PMID- 26141590 TI - The Interface Between Countertransference and Projective Identification in a Case Presented to Peer Supervision. AB - This case report, presented to a supervision group, is a prenatal genetic counseling casethat caused me a great deal of emotional discomfort as the events unfolded. Thediscomfort originated during my first meeting with the couple for routine preamniocentesiscounseling and continued through later encounters. This case illustrates the process ofworking through countertransference and projective identification issues that may arise ingenetic counseling. PMID- 26141591 TI - Caring for the Care-Giver: The Benefit of a Peer Supervision Group. AB - I presented the following case to my leader-led peer supervisiongroup twice as the case evolved over the course of one year. During my firstmeetings with Mr. and Mrs. M we discussed a prenatal diagnosis of a skeletaldysplasia at thirty three weeks of pregnancy and the option of a third trimesterpregnancy termination. One year later I presented follow-up on the outcome ofthe affected pregnancy, a new pregnancy, and Mrs. M's suicide. Although bothsegments of the case were completed by the time I presented, my peersupervision group was invaluable. With the encouragement and support of groupmembers, I could openly express and process my sadness and grief for the M'ssituation and the loss of Mrs. M's life. PMID- 26141592 TI - Closing Thoughts on Supervision. PMID- 26141593 TI - Genetic Library. PMID- 26141594 TI - The rate of in vitro fludarabine-induced peripheral blood and bone marrow cell apoptosis may predict the chemotherapy outcome in patients with chronic lymphocytic leukemia. AB - PURPOSE: The problem of drug sensitivity and predicting the outcome of chemotherapy seems to be of great importance in hemato-oncological disorders. There are some factors that can help to predict effects of chemotherapy in chronic lymphocytic leukemia (CLL), such as presence of del17p, del11q, or TP53 gene mutations, which result in resistance to purine analogues and alkylating drugs. Despite the new therapeutic options introduced recently, purine analogues in combination with cyclophosphamide and the monoclonal antibody rituximab is still the gold standard for the first-line treatment of fit patients with CLL. The aim of this study was to assess whether the rate of apoptosis caused by one of purine analogues-fludarabine in cell cultures differs between patients who clinically respond to fludarabine-based chemotherapy and those who do not respond. METHODS: CLL leukemic cells, obtained from peripheral blood and bone marrow of 23 patients, were cultured in the presence of fludarabine. After 24 h of incubation, the rate of apoptosis, indicated by the expression of active caspase-3, was assessed with flow cytometry and then analyzed regarding clinical response to fludarabine-based regimens. RESULTS: The percentage of apoptotic cells induced by fludarabine was significantly higher in the group of patients who achieved remission in comparison to the group with no response to purine analogues therapy. Interestingly, we observed that among the patients who did not respond to chemotherapy, the presence of del17p and del11q was detected only once. Other non-responders had no detectable genetic abnormalities. CONCLUSIONS: Based on these results, it can be presumed that in vitro drug sensitivity test, which is easy to perform, may predict the outcome of fludarabine-based chemotherapy in CLL patients. PMID- 26141595 TI - The different role of intratumoral and peritumoral lymphangiogenesis in gastric cancer progression and prognosis. AB - BACKGROUND: Tumor-induced lymphangiogenesis plays a crucial role in metastasis and tumor progression. However, the significance of intratumoral lymphovascular density (I-LVD) and peritumoral lymphovascular density (P-LVD) has been controversial in gastric cancer. The purpose of this study was to investigate the differences of clinicopathologic characteristics with respect to I-LVD and P-LVD in gastric cancer. METHODS: Samples of I-LVD and P-LVD from 66 patients who had undergone radical gastrectomy for gastric cancer were assessed after staining with D2-40, an immunostaining marker for lymphatic endothelium. The mean number of lymphatic vessels in three hotspots was calculated in intratumoral and peritumoral areas. RESULTS: The peritumoral lymphatics were enlarged with dilated lumens compared to the intratumoral lymphatics. I-LVD was positively correlated with diffuse gastric cancer subtype, tumor stage, lymphovascular invasion, tumor node metastasis stage, and overall survival (P < 0.05). P-LVD was associated with lymphovascular invasion, node stage, and disease-free survival (P < 0.05). CONCLUSIONS: We conclude that P-LVD had an important role in lymph node metastasis, while I-LVD was more associated with depth of tumor invasion. However, both LVDs contributed to gastric cancer progression and prognosis. PMID- 26141596 TI - The burden of Chikungunya in one coastal department of Colombia (Sucre): Estimates of the disability adjusted life years (DALY) lost in the 2014 epidemic. PMID- 26141597 TI - [Implant-borne prosthetic rehabilitation in patients with cleft lip and palate: A retrospective study on 43 patients]. AB - INTRODUCTION: Implant-borne rehabilitation in cleft lip and palate patient are aimed to allow for good orofacial functions, stable occlusion, and adequate support for the naso-labial region. The goal of our study was to evaluate the functional and esthetic results of the implant-born dental rehabilitation of the cleft lip and palate patients in our department. MATERIAL AND METHODS: Our retrospective study concerned patients operated between 1995 and 2010 in our department. All included patients suffered from a cleft alveolus and lip, with or without cleft palate. Dental implants were placed in the bone-grafted alveolus and the end of growth and at distance from the bone graft procedure. Criteria of implant survival and implant-borne rehabilitation success were defined. RESULTS: A total of 78 implants were placed in 43 patients between 1995 and 2010. Two implants were lost (implant survival rate: 97.4%). Despite this loss, all the patients could be rehabilitated with good functional and esthetic results. DISCUSSION: Implant-borne rehabilitation is a reliable solution for prosthetic rehabilitation in patients with cleft lip and palate. This solution allows for avoiding removable prosthesis and dental mutilation. PMID- 26141598 TI - A comparison of sampling error and standard error. PMID- 26141599 TI - Differential recruitment of UBQLN2 to nuclear inclusions in the polyglutamine diseases HD and SCA3. AB - Accumulation of mutant polyglutamine proteins in intraneuronal inclusions is a hallmark of polyglutamine diseases. Impairment of protein clearance systems and sequestration of clearance-related proteins into inclusions occur in many protein folding diseases, including polyglutamine diseases. The ubiquitin-binding and proteasome adaptor protein UBQLN2 participates in protein homeostasis and localizes to inclusions in various neurodegenerative diseases. Employing mouse models and human brain tissue of Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3), we show that UBQLN2 is selectively recruited to inclusions in HD but not SCA3. Consistent with this result, in a cell-based system mutant HTT interacts with UBQLN2 through the UBA domain while the SCA3 disease protein ATXN3, a deubiquitinating enzyme, does not interact with UBQLN2. Differential recruitment of UBQLN2 to aggregates in HD and SCA3 underscores the heterogeneity of inclusions in polyglutamine diseases and suggests that components of neuronal protein quality control may be differentially perturbed in distinct polyQ diseases. PMID- 26141600 TI - En-bloc resection of thoracic calcified meningioma with inner dural layer in recapping T-saw laminoplasty: a case report. AB - BACKGROUND: In the treatment of spinal cord tumors, complete tumor resection with complete reconstruction of the spine represents the ideal goal. However, for the treatment of heavily calcified spinal meningioma, en-bloc resection of the tumor together with the involved dura at the tumor base through laminectomy is quite difficult. Conventional laminectomy is not wide enough to allow full exposure of such tumors, and postoperative dural defects can cause serious complications. CASE PRESENTATION: A 58-year-old Japanese woman presented with a 3-month history of progressive muscle weakness and numbness of the lower extremities. Magnetic resonance imaging (MRI) and computed tomography showed a calcified spinal cord tumor with dural tail sign at the T10-T11 level, severely compressing the spinal cord anterolaterally. The patient underwent en-bloc resection of the tumor with the inner layer of the dura and preservation of the outer layer of the dura through recapping T-saw laminoplasty of T10-T11, including bilateral facet joints. The tumor was histologically diagnosed as meningioma. Postoperatively, the patient achieved complete recovery of neurological functions. Bone union after laminoplasty was obtained within 6 months. Follow-up MRI at 5 years postoperatively demonstrated no recurrence of the tumor. CONCLUSION: Resection of spinal meningioma with only the inner layer of dura can minimize postoperative complications, including spinal fluid leakage. Recapping T-saw laminoplasty provides extensive exposure for tumor removal. The combination of these techniques may offer an ideal surgical option for complete resection of spinal meningioma with complete preservation of the posterior spinal elements. PMID- 26141601 TI - Differences in parent regulation beliefs and maternal postnatal depressive symptoms in early weeks. AB - Postnatal depression is consistently associated with couple relationship qualities. Substantial infant care requirements in early weeks may highlight differences in parenting beliefs between mother and father. We calculated difference scores in parenting beliefs (disparity) in a community sample of 209 parent dyads. Contrary to previous research regarding 'disagreement' which could be interpreted as discord, independently measured disparity was not associated with maternal depressive symptoms. Coparenting interventions should promote respectful negotiation rather than resolution of differences. PMID- 26141602 TI - Reactivity to 35% carbon dioxide in bulimia nervosa and panic disorder. AB - The inhalation of 35% carbon dioxide (CO2) induces panic and anxiety in people with panic disorder (PD) and in people with various other psychiatric disorders. The anxiogenic effect of CO2 in people with eating disorders has received sparse attention despite the fact that PD and bulimia nervosa (BN) have several common psychological and neurobiological features. This study compared CO2-reactivity across three groups of participants: females with BN, females with PD, and female controls without known risk factors for enhanced CO2-reactivity (e.g., social anxiety disorder, first degree relatives with PD). Reactivity was measured by self-reported ratings of panic symptomatology and subjective anxiety, analyzed as both continuous variables (change from room-air to CO2) and dichotomous variables (positive versus negative responses to CO2). Analyses of each outcome measure demonstrated that CO2-reactivity was similar across the BN and PD groups, and reactivity within each of these two groups was significantly stronger than that in the control group. This is the first study to demonstrate CO2-hyperreactivity in individuals with BN, supporting the hypothesis that reactivity to this biological paradigm is not specific to PD. Further research would benefit from examining transdiagnostic mechanisms in CO2-hyperreactivity, such as anxiety sensitivity, which may account for this study's results. PMID- 26141603 TI - Anxiety control and metacognitive beliefs mediate the relationship between inflated responsibility and obsessive compulsive symptoms. AB - Research has indicated that beliefs about inflated responsibility, beliefs about perceived control over anxiety-related events and reactions (anxiety control) and metacognitive beliefs about the need to control thoughts are associated with obsessive compulsive symptoms. In the current study we tested a mediation model of the interactions between these variables in predicting obsessive compulsive symptoms. Thirty-seven individuals with obsessive compulsive disorder and 31 controls completed the following self-report instruments: the Responsibility Attitude Scale, the Anxiety Control Scale, the Beliefs about Need to Control Thoughts sub-scale of the Metacognitions Questionnaire 30, and the Padua Inventory. Mann-Whitney U tests revealed that participants in the clinical group scored significantly higher than those in the non-clinical group on all variables. In the mediation model we found that the relationship between beliefs about inflated responsibility and obsessive compulsive symptoms was fully mediated by anxiety control and beliefs about the need to control thoughts. These findings provide support for the significant role played by beliefs about control in predicting the severity of obsessive compulsive symptoms. PMID- 26141604 TI - MicroRNA-196b is transcribed from an autonomous promoter and is directly regulated by Cdx2 and by posterior Hox proteins during embryogenesis. AB - The miR-196 miRNA gene family located within the Hox gene clusters has been shown to function during embryogenesis and to be aberrantly expressed in various malignancies, including leukaemia, melanoma, and colorectal cancer. Despite its involvement in numerous biological processes, the control of miR-196 expression is still poorly defined. We identified the miR-196b promoter and found that the mature miR-196b originates from a large, non-coding primary transcript, which starts within an autonomous TATA box promoter and is not in physical continuity with either the Hoxa10 or Hoxa9 main primary transcripts. A ~680bp genomic fragment, spanning the pri-miR-196b transcription start site, is sufficient to recapitulate the neural tube expression pattern of miR-196 during embryogenesis. This region contains potential binding sites for Cdx and 5'Hox transcription factors. Two of these sites revealed to be necessary for neural tube expression and were bound in vivo by Cdx2 and Hoxd13. We show that Cdx2 is required for miR 196 expression and that both Cdx2 and 5'Hox, but not 3'Hox, are able to activate the miR-196b promoter. The possible role of Cdx2- and 5'Hox-mediated regulation of miR-196 expression in vertebrate anterior-posterior (AP) axis formation during embryogenesis is discussed. PMID- 26141606 TI - Environmental risk factors of systemic sclerosis. AB - Systemic sclerosis (SSc) has a complex pathogenesis. Although, there is a growing evidence that environmental factors have an impact on alterations and modulation of epigenetic determinants, resulting in SSc onset and progression. A marked correlation has thus been found between SSc onset and occupational exposure to crystalline silica and the following organic solvents: white spirit, aromatic solvents, chlorinated solvents, trichloroethylene, and ketones; the risk associated with high cumulative exposure to silica and organic solvents further appears to be strongly increased in SSc. Altogether, occupational exposure should be systematically checked in all SSc patients at diagnosis, as (1) exposed patients seem to develop more severe forms of SSc and (2) the identification of the occupational agents will allow its interruption, which may lead to potential improvement of SSc outcome. By contrast, based on current published data, there is insufficient evidence that exposure to other chemical agents (including notably pesticides as well as personal care such as silicone and hair dye), physical agents (ionizing radiation, ultraviolet radiation, electric and magnetic fields), and biological agents (infections and diet, foods, and dietary contaminants) is a causative factor of SSc. Further investigations are still warranted to identify other environmental factors that may be associated with SSc onset and progression. PMID- 26141607 TI - Matrix remodeling in systemic sclerosis. AB - Systemic sclerosis (SSc, scleroderma) is an often-fatal disease characterized by connective tissue fibrosis of skin and internal organs. In scleroderma, there is an excessive production and accumulation of extracellular matrix (ECM) components resulting from an increase in collagen synthesis and matrix stability. Understanding how this how excessive ECM is produced and remodeled may represent a novel therapeutic approach. In this review, the transcription factors and collagen-modifying enzymes underlying collagen overexpression and enhancing stability in SSc are discussed. Moreover, the role of matrix stiffness in promoting fibrosis via a feed-forward mechanism is discussed. Indeed, the emerging evidence is that enhanced ECM remodeling resulting in increased ECM stiffness may be sufficient in itself to sustain persistence fibrosis in SSc. PMID- 26141609 TI - Bone as a classic endocrine organ: Interactions with non-bone tissues. PMID- 26141605 TI - Long noncoding RNAs in diseases of aging. AB - Aging is a process during which progressive deteriorating of cells, tissues, and organs over time lead to loss of function, disease, and death. Towards the goal of extending human health span, there is escalating interest in understanding the mechanisms that govern aging-associated pathologies. Adequate regulation of expression of coding and noncoding genes is critical for maintaining organism homeostasis and preventing disease processes. Long noncoding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression at all levels- transcriptional, post-transcriptional and post-translational. In this review, we discuss our emerging understanding of lncRNAs implicated in aging illnesses. We focus on diseases arising from age-driven impairment in energy metabolism (obesity, diabetes), the declining capacity to respond homeostatically to proliferative and damaging stimuli (cancer, immune dysfunction), and neurodegeneration. We identify the lncRNAs involved in these ailments and discuss the rising interest in lncRNAs as diagnostic and therapeutic targets to ameliorate age-associated pathologies and prolong health. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26141608 TI - Fibrogenesis, novel lessons from animal models. AB - Systemic sclerosis (SSc) is a devastating chronic autoimmune connective tissue disease characterized by vasculopathy, autoimmunity with inflammation, and progressive fibrogenesis. The current paradigm of the pathogenesis of SSc is that of an unknown initial trigger, leading to a complex interaction of immune cells, endothelial cells, and fibroblasts, producing cytokines, growth and angiogenic factors, and resulting in uncontrolled and persistent tissue fibrogenesis by an altered mesenchymal cell compartment. Animal models are of utmost importance to investigate the different steps in the pathogenesis. This review will elaborate on recent findings in established and more recently developed animal models, presenting data on compounds that are in or ready to be translated into clinical trials, or provide interesting new findings in the understanding of the pathophysiology of SSc. We focus on recent findings concerning the vessel extracellular matrix interaction, the initial triggering aggressor, the concept of autoimmunity and inflammatory changes, the effector cells and their origins, and the complex interaction of the different signaling pathways in fibrogenesis. PMID- 26141610 TI - Long-term exposure to high glucose increases the content of several exocytotic proteins and of vesicular GABA transporter in cultured retinal neural cells. AB - Diabetic retinopathy is a leading cause of vision loss and blindness. Increasing evidence has shown that the neuronal components of the retina are affected even before the detection of vascular lesions. Hyperglycemia is considered the main pathogenic factor for the development of diabetic complications. Nevertheless, other factors like neuroinflammation, might also contribute for neural changes. To clarify whether hyperglycemia can be the main trigger of synaptic changes, we evaluated whether prolonged elevated glucose per se, mimicking chronic hyperglycemia, is able to change the content and distribution of several exocytotic proteins and vesicular glutamate and GABA transporters in retinal neurons. Moreover, we also tested the hypothesis that an inflammatory stimulus (interleukin-1beta) could exacerbate the effects induced by exposure to elevated glucose, contributing for changes in synaptic proteins in retinal neurons. Rat retinal neural cells were cultured for 9 days. Cells were exposed to elevated D glucose (30 mM) or D-mannitol (osmotic control), for 7 days, or were exposed to interleukin-1beta (10 ng/ml) or LPS (1 MUg/ml) for 24 h. The protein content and distribution of SNARE proteins (SNAP-25, syntaxin-1, VAMP-2), synapsin-1, synaptotagmin-1, rabphilin 3a, VGluT-1 and VGAT, were evaluated by western blotting and immunocytochemistry. The protein content and immunoreactivity of syntaxin-1, synapsin-1, rabphilin 3a and VGAT increased in retinal neural cells exposed to high glucose. No changes were detected when cells were exposed to interleukin-1beta, LPS or mannitol per se. Particularly, exposure to interleukin 1beta for 24 h did not exacerbate the effect of high glucose on the content and immunoreactivity of exocytotic proteins, suggesting the primordial role of hyperglycemia for neuronal changes. In summary, prolonged exposure to elevated glucose alters the total content of several proteins involved in exocytosis, suggesting that hyperglycemia per se is a fundamental factor for neuronal changes caused by diabetes. PMID- 26141611 TI - Unilateral microinjection of carbenoxolone into the pontis caudalis nucleus inhibits the pentylenetetrazole-induced epileptiform activity in rats. AB - Pontine reticular formation (PRF) is involved in the generation and maintenance of generalized epileptic seizures. Carbenoxolone (CBX) is a gap junction blocker with anticonvulsant properties. Therefore, the present study was designed to explore the effects of CBX microinjected into the pontis caudalis nucleus (PnC) on generalized tonic-clonic seizures (GTCS) and epileptiform activity induced by pentylenetetrazole (PTZ). All control rats presented GTCS after a single dose of PTZ. The microinjection of CBX into the PnC reduced the GTCS incidence induced by PTZ. Moreover, the CBX significantly increased the latency to the first myoclonic jerk. Additionally, CBX significantly decreased the spectral power and the amplitude of the epileptiform activity induced by PTZ. By contrast, the microinjection of a gap junction opener (trimethylamine) did not cause anticonvulsant effects and even increased the duration of the GTCS. These findings suggest that the PnC is a particular nucleus where the CBX could exert its action mechanisms and elicit anticonvulsant effects. PMID- 26141612 TI - Neuroprotective effects of bisperoxovanadium on cerebral ischemia by inflammation inhibition. AB - PTEN is a dual specificity phosphatase and is implicated in inflammation and apoptosis of cerebral ischemia and reperfusion (I/R) injury. Bisperoxovanadium (Bpv), a specific inhibitor of PTEN's phosphatase activity, has demonstrated powerful neuroprotective properties. We investigated the neuroprotective roles of Bpv in the rat model of middle cerebral artery occlusion (MCAO) cerebral I/R injury, and explored the modulation of inflammatory mediators and PI3K/Akt/GSK 3beta pathways by Bpv. Our results showed that treatment with Bpv (0.2 mg/kg/day) significantly decreased neurological deficit scores at 7 days after MCAO and infarct volume at 4 days after MCAO. The IL-10 concentration was increased and TNF-alpha concentration was decreased in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO by Bpv. Furthermore, Bpv (0.2 mg/kg/day) treatment significantly reduced PTEN mRNA and protein levels and increased PI3K, Akt and p-GSK-3beta proteins expression in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO. In conclusions, Bpv treatment demonstrates neuroprotective effects on cerebral ischemia and reperfusion injury of ischemic stroke rats and is associated with its modulation of inflammatory mediator production and up-regulation of PTEN downstream proteins PI3K, Akt and p-GSK 3beta. PMID- 26141613 TI - Peptide-functionalized polymeric nanoparticles for active targeting of damaged tissue in animals with experimental autoimmune encephalomyelitis. AB - Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS. PMID- 26141614 TI - Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability. AB - A panel of cerebrospinal fluid (CSF) biomarkers including total Tau (t-Tau), phosphorylated Tau protein at residue 181 (p-Tau) and beta-amyloid peptides (Abeta42 and Abeta40), is frequently used as an aid in Alzheimer's disease (AD) diagnosis for young patients with cognitive impairment, for predicting prodromal AD in mild cognitive impairment (MCI) subjects, for AD discrimination in atypical clinical phenotypes and for inclusion/exclusion and stratification of patients in clinical trials. Due to variability in absolute levels between laboratories, there is no consensus on medical cut-off value for the CSF AD signature. Thus, for full implementation of this core AD biomarker panel in clinical routine, this issue has to be solved. Variability can be explained both by pre-analytical and analytical factors. For example, the plastic tubes used for CSF collection and storage, the lack of reference material and the variability of the analytical protocols were identified as important sources of variability. The aim of this review is to highlight these pre-analytical and analytical factors and describe efforts done to counteract them in order to establish cut-off values for core CSF AD biomarkers. This review will give the current state of recommendations. PMID- 26141615 TI - Effect of hypoxia on heart rate variability and baroreflex sensitivity during hypoglycemia in type 1 diabetes mellitus. AB - PURPOSE: Patients with type 1 diabetes mellitus exhibit impairments in autonomic and cardiovascular control which are worsened with acute hypoglycemia--thus increasing the risk of adverse cardiovascular events. Hypoxia, as seen with the common comorbidity of sleep apnea, may lead to further autonomic dysfunction and an increased risk of ventricular arrhythmias. Therefore, we hypothesized that heart rate variability (HRV) and baroreflex sensitivity (BRS) would be reduced during hypoglycemia in adults with type 1 diabetes, with a further decline when combined with hypoxia. METHODS: Subjects with type 1 diabetes (n = 13; HbA1c = 7.5 +/- 0.3 %, duration of diabetes = 17 +/- 5 yrs) completed two 180 min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 umol/mL) clamps separated by a minimum of 1 week and randomized to normoxia (SpO2 ~98 %) or hypoxia (SpO2 ~85 %). Heart rate (electrocardiogram) and blood pressure (finger photoplethysmography) were analyzed at baseline and during the hypoglycemic clamp for measures of HRV and spontaneous cardiac BRS (sCBRS). RESULTS: Hypoglycemia resulted in significant reductions in HRV and sCBRS when compared with baseline levels (main effect of hypoglycemia: p < 0.05). HRV and sCBRS were further impaired during hypoxia (main effect of hypoxia: p < 0.05). CONCLUSIONS: Acute hypoxia worsens hypoglycemia-mediated impairments in autonomic and cardiovascular control in patients with type 1 diabetes and may increase the risk of cardiovascular mortality. These results highlight the potential cumulative dangers of hypoglycemia and hypoxia in this vulnerable population. PMID- 26141616 TI - Distinct expression patterns of HCN channels in HL-1 cardiomyocytes. AB - BACKGROUND: Cardiac rhythmic activity is initiated in functionally specialized areas of the heart. Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are fundamental for these processes of cardiac physiology. RESULTS: Here we investigated transcript and protein expression patterns of HCN channels in HL 1 cardiomyocytes using a combination of quantitative PCR analysis and immunocytochemistry. Gene expression profiles of hcn1, hcn2 and hcn4 were acutely affected during HL-1 cell propagation. In addition, distinct expression patterns were uncovered for HCN1, HCN2 and HCN4 proteins. CONCLUSIONS: Our results suggest that HCN channel isoforms might be involved in the concerted differentiation of HL-1 cells and may indirectly affect the occurrence of contractile HL-1 cell activity. We expect that these findings will promote studies on other molecular markers that contribute to cardiac physiology. PMID- 26141617 TI - Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study. AB - BACKGROUND: ABCA7 was identified as a risk gene for Alzheimer's disease in genome wide association studies (GWAS). It was one of the genes most strongly associated with risk of Alzheimer's disease in a Belgian cohort. Using targeted resequencing, we investigated ABCA7 in this cohort with the aim to directly detect rare and common variations in this gene associated with Alzheimer's disease pathogenesis. METHODS: We did massive parallel resequencing of ABCA7 after HaloPlex target enrichment of the exons, introns, and regulatory regions in 772 unrelated patients with Alzheimer's disease (mean age at onset 74.6 years [SD 8.9]) recruited at two memory clinics in Flanders, Belgium, and 757 geographically matched community-dwelling controls (mean age at inclusion 73.9 years [8.0]). After bioinformatic processing, common variants were analysed with conditional logistic regression and rare variant association analysis was done in Variant Association Tools. To explore an observed founder effect, additional unrelated patients with Alzheimer's disease (n=183, mean age at onset 78.8 years [SD 6.0]) and control individuals (n=265, mean age at inclusion 56.9 years [10.8]) from the same cohort who had not been included in massive parallel resequencing because of insufficient biosamples were screened for the ABCA7 frameshift mutation Glu709fs with Sanger sequencing. The effect of loss-of function mutations on ABCA7 expression was investigated with quantitative real time PCR in post-mortem brains of patients (n=3) and control individuals (n=4); nonsense mediated mRNA decay was investigated in lymphoblast cell lines from three predicted loss-of-function mutation carriers from the cohort of 772 patients with Alzheimer's disease. FINDINGS: An intronic low-frequency variant rs78117248 (minor allele frequency 3.8% in 58 patients with Alzheimer's disease and in controls 1.8% in 28 controls) showed strongest association with Alzheimer's disease (odds ratio 2.07, 95% CI 1.31-3.27; p=0.0016), and remained significant after conditioning for the GWAS top single nucleotide polymorphisms rs3764650, rs4147929, and rs3752246 (2.00, 1.22-3.26; p=0.006). We identified an increased frequency of predicted loss-of-function mutations in the patients compared with the controls (relative risk 4.03, 95% CI 1.75-9.29; p=0.0002). One frameshift mutation (Glu709fs) showed a founder effect in the study population, and was found to segregate with disease in a family with autosomal dominant inheritance of Alzheimer's disease. Expression of ABCA7 was reduced in the two carriers of loss-of-function mutations found only in patients with Alzheimer's disease (Glu709fs and Trp1214*) compared with four non-carrier controls (relative expression 0.45, 95% CI 0.25-0.84; p=0.002) and in lymphoblast cell lines from three carriers of Glu709fs compared with those from two non-carrier controls. INTERPRETATION: We propose that a low-frequency variant can explain the association between ABCA7 and Alzheimer's disease, and the evidence of loss-of function mutations in this risk gene suggests that partial loss-of-function of ABCA7 could be a potential pathogenetic mechanism of Alzheimer's disease. FUNDING: Belgian Science Policy Office Interuniversity Attraction Poles program P7/16, Alzheimer Research Foundation, King Baudouin Foundation AB Fund, Methusalem Excellence Program initiative of the Flemish Government, Flanders Impulse Program on Networks for Dementia Research, Research Foundation Flanders, Agency for Innovation by Science and Technology Flanders, University of Antwerp Research Fund, and European Union's Seventh Framework Programme for Research, Technological development and Demonstration (AgedBrainSYSBIO). PMID- 26141618 TI - Expanding the genomic roadmap of Alzheimer's disease. PMID- 26141619 TI - [In Process Citation]. PMID- 26141620 TI - Rational Combination of Immunotherapies with Clinical Efficacy in Mice with Advanced Cancer. AB - In the context of cancer, naive T cells are insufficiently primed and become progressively dysfunctional. Boosting antitumor responses by blocking PD-1 or CTLA-4 results in durable clinical responses only in a limited proportion of cancer patients, suggesting that other pathways must be targeted to improve clinical efficacy. Our preclinical study in TRAMP mice comparing 14 different immune interventions identified anti-CD40 + IL2/anti-IL2 complexes + IL12Fc as a uniquely efficacious treatment that prevents tolerance induction, promotes priming of sustained, protective tumor-specific CD8(+) T cells, and cures late stage cancer when given together with adoptively transferred tumor-specific T cells. We propose that improving signals 2 (costimulation) and 3 (cytokines) together with fresh tumor-specific, rather than boosting of dysfunctional preexisting memory, T cells represents a potent therapy for advanced cancer. PMID- 26141621 TI - What's new in melanoma? Combination! AB - Melanoma was again a focus of attention at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, in particular the use of combination treatment strategies involving immunotherapies and/or targeted agents. New data on targeted therapies confirmed previous findings, with combined BRAF inhibitor (vemurafenib) plus MEK inhibitor (cobimetinib) improving progression-free survival (PFS) compared to vemurafenib monotherapy in patients with BRAFV600 mutation-positive tumors (CoBRIM trial). Positive results were also seen with combined dabrafenib and trametinib in patients with BRAF V600E/K metastatic melanoma and encorafenib plus binimetinib in BRAFV600-mutant cutaneous melanoma. Even more interesting news centered on the use of combination immunotherapy, in particular the randomized, double-blind CheckMate 067 study in which median PFS with nivolumab plus ipilimumab was 11.5 months, compared to 2.9 months with ipilimumab alone (HR 0.42) and 6.9 months with nivolumab alone (HR 0.57). Of interest, in patients with >=5% PD-L1 expression, median PFS was 14 months with the combination or with nivolumab alone compared with 3.9 months in the ipilimumab group, while in the PD L1 negative cohort, the combination remained superior to both monotherapies. Given that combination therapy was accompanied by a high occurrence of side effects, this raises the suggestion that combination therapy might be reserved for PD-L1 negative patients only, with PD-L1 positive patients achieving the same benefit from nivolumab monotherapy. However, overall survival data are awaited and the equivalence of single agent to the combination remains unconvincing. Interesting data were also reported on the combination of T-VEC (talimogene laherparepvec) with ipilimumab, and the anti-PD-1 agent MEDI4736 (durvolumab) combined with dabrafenib plus trametinib. Emerging data also suggested that predictive markers based on immunoprofiling and mismatch repair deficiency may be of clinical use. In conclusion, the use of combination approaches to treat patients with melanoma, as well as other cancers, is no longer a just a wish for the future but is today a clinical reality with a rapidly growing evidence-base. Moreover, the most exciting consideration is that this is far from the end of the story, but rather a fantastic introduction. PMID- 26141623 TI - Evaluation of recombinant leukocidin domain of VvhA exotoxin of Vibrio vulnificus as an effective toxoid in mouse model. AB - Vibrio vulnificus hemolysin A (VvhA) is a pore forming toxin and plays an important role in the pathogenesis. The hemolytic and cytotytic property of VvhA toxin is associated with N-terminal leukocidin domain which triggers apoptotic signaling cascade in epithelial cells. The present study was undertaken to assess the protective efficacy of recombinant VvhA leukocidin domain (rL/VvhA) against VvhA toxin challenge using in vitro and in vivo assays. The rL/VvhA protein was found to be non-toxic with no significant hemolytic or cytotoxic effects. Intraperitoneal (I.P.) immunization of BALB/c mice with rL/VvhA protein elicited significantly higher specific serum antibody titer with mixed Th1/Th2 mediated immune responses. HeLa cell monolayer supplemented with anti-rL/VvhA antibodies were effectively protected (viability 86.69%) against lethal 5 LD50 toxin challenge. An effective in vitro proliferation of lymphocyte was observed upon re stimulation of rL/VvhA primed splenocytes with formalin inactivated VvhA toxin (fVvhA). Co-expression of Th1/Th2 polarized cytokines (IFN-gamma, IL-12 and IL 4), were seen in the cell culture supernatant. In contrast to sham immunized mice, rL/VvhA immunized mice demonstrated significant protection (90% survival) against native toxin challenge in vitro and in vivo infection models. These results suggested leukocidin domain of the VvhA toxin as protective immunogen for possible protection against V. vulnificus VvhA. PMID- 26141622 TI - Obesity: physiologic changes and implications for preoperative management. AB - The proportion of patients defined as obese continues to grow in many westernized nations, particularly the United States (USA). This trend has shifted the perioperative management of obese patients into the realm of routine care. As obese patients present for all types of procedures, it is crucial for anesthesiologists, surgeons, internists, and perioperative health care providers alike to have a firm understanding of their altered multi-organ physiology in order to safely prepare the obese patient for an operation. A careful preoperative evaluation may also serve to identify risk factors for postoperative adverse events. Subsequently, preoperative measures may be implemented to mitigate these complications. In this manuscript we address the major considerations for the preoperative evaluation of the severely obese patient. PMID- 26141624 TI - CpG-A stimulates Hsp72 secretion from plasmacytoid dendritic cells, facilitating cross-presentation. AB - Plasmacytoid dendritic cells (pDCs) are the main producers of IFN-alpha in response to unmethylated DNA molecules, including cytosine guanine dinucleotide (CpG)-DNA in vivo. pDCs specifically express toll-like receptor (TLR) 9 and are therefore able to recognize the unmethylated DNAs. It has recently been shown that not only conventional DCs (cDCs) but also pDCs efficiently cross-present exogenous antigens after TLR9 activation. However, the precise molecular mechanism has remained unclear. Here, we show that pDCs secreted heat shock protein 72 (Hsp72) in response to CpG-A administration in a TLR9-dependent manner. Extracellular Hsp72 bound to an Hsp90-peptide complex and enhanced binding of Hsp90-peptide complex to pDC, resulting in efficient cross presentation. Our experiments therefore suggest a mechanism for orchestration of immune responses by stimulation of pDCs with CpG-A. PMID- 26141625 TI - Identification of dopamine- and serotonin-related genes modulated by bisphenol A in the prefrontal cortex of male rats. AB - There is concern that exposure of embryos and/or infants to bisphenol A (BPA) may lead to neurological and behavioral disorders with unknown prefrontal cortex (PFC) involvement. Critical PFC functions are modulated by dopamine (DA) and serotonin (5-HT) systems, whose alterations have been associated with psychopathologies that may appear in youth and/or adulthood. This study aims to determine in the PFC of male rats exposed to a low dose of BPA (10MUgkg(-1)d(-1)) from gestational day 12 (GD12) to postnatal day 21 (PND21): (i) DA- and 5-HT related genes modulated by BPA at the juvenile stage (PND21); (ii) reversible and irreversible transcriptional effects; (iii) long-term consequences (effects in adult rats, PND90). In juvenile rats, BPA altered significantly the transcription of 12 out of the 84 genes analyzed using PCR-array techniques. Interestingly, transcript levels of the neurotrophic factor Gdnf were decrease by BPA in both juvenile and adult rats. At adulthood, disruptions in genes encoding rate limiting enzymes for DA and 5-HT synthesis emerged. Overall, the results indicate that early-life exposure to BPA has consequences on DA and 5-HT systems in both juvenile- and adult-life stages. Additionally, we reveal molecular targets that could provide the foundation for future BPA neurotoxicity studies. PMID- 26141626 TI - Beth Fine Kaplan-Colleague and Friend. PMID- 26141627 TI - Demographic Studies from a National Gaucher Disease Screening Program. AB - In May 1993, the National Gaucher Foundation initiated a nationwide Gaucher disease screening program in an attempt to promote recognition of the disease and to detect previously undiagnosed individuals. The program was based on self selection by clinical symptoms of individuals who wanted to be tested for Gaucher disease. Information about symptoms, age, ancestry, gender, and family history was obtained via a self-report screening form completed by 700 individuals. Individuals designated at "high risk" for Gaucher disease were offered beta glucocerebrosidase enzyme assay testing. Twenty-four of the respondents (3.4%) had Gaucher disease. The most commonly reported symptoms were fatigue (79.4%), bone pain (73.7%), and tendency to bruise (67.8%). The symptoms which showed a statistical difference between the "high risk" and "low risk" groups were liver enlargement (p < 0.005) and unexplained bone fractures (p < 0.03). The mean number of positive symptoms also showed a statistical difference between the groups (4.38 symptoms vs. 3.86 symptoms; p < 0.02). Due to the small sample size, no statistical comparisons were made on the symptomatology of affected vs. unaffected persons, but a descriptive analysis of these two groups is reported. PMID- 26141628 TI - Continuation of Pregnancy Following the Diagnosis of a Fetal Sex Chromosome Abnormality: A Study of Parents' Counseling Needs and Experiences. AB - Parents who decide to continue a pregnancy diagnosed with a sex chromosome abnormality (SCA) experience a variety of emotions as they deal with complex medical and genetic information. To better understand these individuals' psychosocial, educational, and support needs, 26 parents who received prenatal diagnosis of an SCA after 1989 and who had decided to continue their pregnancy were interviewed by telephone. Twenty (77%) reported they initially had a "poor" understanding of the predicted syndrome. All parents later met with a genetics professional. Twenty-two (92%) parents considered sterility and underdevelopment of secondary sexual characteristics to be the most negative aspects of SCAs. Contact with other parents of children with SCAs and with support organizations were generally viewed as helpful experiences. Insight gained from this study should be useful for genetic counselors and other health care providers involved with patients who have received abnormal prenatal diagnosis results. PMID- 26141629 TI - The Effect of Genetic Counseling on Knowledge and Perceptions Regarding Risks for Breast Cancer. AB - In 1994, a clinic for cancer risk counseling was opened at Hadassah University Hospital in Jerusalem. Most of the counselees have been women who had breast cancer and/or a relative with breast cancer. In order to evaluate the effect of this counseling on women's knowledge and perceptions regarding the risks for breast cancer, a questionnaire was given before and after the counseling session to 60 healthy women who came to the clinic because they have relatives with breast cancer. According to the genetic counselors' estimations, most of these women had a significantly increased risk (compared to the general population) of developing cancer. Before counseling, the women overestimated the population risk for breast cancer, the contribution of heredity to morbidity of cancer, and their own risks to get cancer. After counseling session, they gave reduced estimates, closer to the "real" ones. The subjective perceptions regarding these risks were reduced after counseling, except for the perceptions regarding their relativerisks which have not changed after the counseling. About 90% of the women who came to the clinic wanted to be tested for genetic predisposition to cancer. For most of these women, the expectations that the test can rule out a genetic predisposition to cancer became more realistic after the counseling. The option to first test an affected relative was offered to all families, and a test was actually conducted in 75% of the families. PMID- 26141630 TI - Genetic Library. PMID- 26141631 TI - Ulcerative Colitis Symptomatology and Depression: The Exacerbator Role of Maladaptive Psychological Processes. AB - BACKGROUND: Several studies have indicated that depressive symptomatology plays a pertinent role in the clinical recurrences of ulcerative colitis (UC). Due to the self-perpetuating cycle between UC symptomatology and depressive mood, it is considered that more investment should be given to the study of factors that influence depressive symptomatology in UC patients. AIMS: This study aimed therefore at analyzing the exacerbator effect of maladaptive psychological strategies, such as cognitive fusion and brooding, on the relationship between UC symptomatology and depressive symptoms. METHODS: The sample of the current study included 84 Portuguese patients with UC that completed an Internet-based survey (comprising demographic and medical questions, and self-report measures of depression, cognitive fusion, and brooding). RESULTS: Results showed that UC symptomatology explained 21% of depression severity's variance. In addition, a significant interaction between UC symptomatology and cognitive fusion was found and explained 50% of depressive symptoms' severity. A similar interaction was revealed between UC symptomatology and brooding, which accounted for 42% of depression's variance. These findings demonstrated that, for the same level of UC symptomatology, those participants who revealed more cognitive fusion or more brooding presented significant higher levels of depression. CONCLUSIONS: The present study revealed cognitive fusion and brooding as moderators that exacerbate the impact of UC symptomatology on reported levels of depression. Psychological interventions that focus on the promotion of adaptive emotion regulation strategies to deal with adverse and stressful events should therefore be developed and implemented in UC patients' health care. PMID- 26141632 TI - Establishment and characterization of SUIT-58 pancreas cancer cell line and its subline S58-SF adapted to serum-free condition derived from metastatic liver tumor. AB - A new pancreas cancer cell line, SUIT-58, was established from metastatic liver tumor. The cultured cells exhibited polygonal shape, and proliferated in a form of sheet-structure showing prominent nucleoli and frequent mitotic features. Chromosome count ranged from 54 to 73 with modal chromosome numbers 72 and 73. It was noteworthy that this cell line grew in the serum-free media and maintained in this condition for 30 passages (designated as S58-SF). Both SUIT-58 and S58-SF cell lines were successfully transplanted into nude mice, and their tumor doubling times in xenografts were calculated as 5.4 and 2.8 days, respectively. Histopathologically, the xenografts formed glandular structure that resembled the original tumor. In culture media, the doubling time of SUIT-58 and S58-SF cell lines was calculated as 32 and 35.7 h, respectively. Although the cellular arrangements of SUIT-58 and S58-SF cell lines are different to some extent, their subcellular structures under electron microscope were similar with a large number of lysosomes and distinct desmosomes at cell-cell adhesion sites. The present SUIT-58 and its derivative cell line S58-SF will be applicable for biological studies to develop a new clinical treatment of refractory pancreatic cancer. PMID- 26141633 TI - Potential roles of gonadotropins to control pulsatile retinoic acid signaling during spermatogenesis. AB - Spermatogenesis is a highly regulated process that takes place in the seminiferous tubules of testis. This process initiates at puberty with differentiation of spermatogonia and their meiotic entry. The initiation of spermatogenesis depends on gonadotropins secreted by the pituitary gland; i.e., follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In the absence of FSH and LH only premeiotic germ cells are present in the testis. The prepubertal development phase in juvenile testis is characterized by a protracted hypogonadotropic state, which only consists of Sertoli and undifferentiated germ cells in the seminiferous epithelium. All germ cells in the juvenile testis are undifferentiated spermatogonia, which are proliferating in a relatively gonadotropin-independent manner. It has been revealed that vitamin A deficient (VAD) animals are also infertile, and only premeiotic germ cells (undifferentiated spermatogonia) are present in their seminiferous tubules. The developmental block in VAD animal can be removed by administration of retinol and germ cell differentiation reinitiates in a synchronous manner. Recent studies have revealed that the biologically active form of vitamin A, retinoic acid (RA), regulates germ cell differentiation and lead to the generation of the cycle of the seminiferous epithelium and normal spermatogenic wave. Recent study has shown that synchronous spermatogenesis at neonatal mouse, but not after initiation of meiosis, can be induced by treating vitamin A sufficient males with RA. The treatment of neonatal males at different ages with exogenous RA has revealed that although RA is sufficient to induce differentiation of spermatogonial at 4 dpp and earlier, it fails to alter asynchrony and it does not irreversibly cause a spermatogonial differentiation. These observations led us to suggest that gonadotropins trigger differentiation of spermatogonia and spermatogenesis through regulation of RA signaling in the seminiferous epithelium of the adult testis. PMID- 26141634 TI - A hypothesis on possible neurochemical mechanisms of action of cervical spinal cord stimulation in prevention and treatment of cerebral arterial vasospasm after aneurysmal subarachnoid hemorrhage. AB - Subarachnoid hemorrhage (SAH) is associated with the high incidence of development of cerebral vasospasm that results in morbidity and mortality due to delayed cerebral ischemia. So far there are no consistently effective therapies for treatment of vasospasm in patients suffering from SAH. It is well known that cervical spinal cord stimulation (SCS) can induce vasodilatation and increase cerebral blood flow (CBF). Based on the experiments in animals and the studies in humans, we have proposed the possibility to use SCS as a therapeutic strategy for prevention and treatment of cerebral vasospasm after SAH. However, the physiological mechanisms of action of SCS in this regard are poorly understood. Better understanding of the pathophysiology of vasospasm after SAH may provide insight into the role of SCS in such conditions. We hypothesize that effect of SCS on vasodilatation may be related to modulation of activity of phosphodiesterases 5 (PDE-5) and nitric oxide synthase (eNOS), resulting in enhancement of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, which may help prevent and/or treat vasospasm after SAH. Further investigations on the physiological mechanisms of action of SCS would be necessary to support this hypothesis. PMID- 26141635 TI - Intravenous infusion of haptoglobin for the prevention of adverse clinical outcome in Sickle Cell Disease. AB - Sickle Cell Disease (SCD) is a genetic condition which manifests as altered hemoglobin (Hb) protein that can aggregate under hypoxic conditions. The resultant sickled erythrocytes experience premature hemolysis, releasing an estimated 10g of free Hb (fHb) into the intravascular space. FHb participates in redox reactions creating various reactive oxygen species which rapidly and irreversibly scavenge nitric oxide, thereby attenuating its vasodilatory, antithrombotic, and anti-inflammatory properties. FHb also induces endothelial expression of adhesion molecules, triggering leukocyte margination at the vessel wall. These mechanisms participate in diverse SCD-associated clinical events including nephropathy, pulmonary hypertension, chronic leg ulceration, and ischemic events. FHb also exerts a direct reno-toxic effect contributing to albuminuria which is an early, frequent manifestation of glomerular injury. Under normal conditions, fHb is effectively scavenged by the Hb-scavenging mechanism (HSM); this involves binding to haptoglobin (Hp), uptake via the Hb-scavenging receptor (CD163) on monocytes and metabolism by heme-oxygenase-1. This culminates in increased CD163 expression and release of anti-inflammatory by-products e.g. interleukin-10 (IL-10). In SCD, the Hb-binding capacity is overwhelmed by chronic hemolysis; our previous research shows serum Hp as the depleted component. This deficiency could result in the harmful consequences of circulating fHb going unbridled. The hypothesis we explore here is that Hp infusions, in excess of fHb concentration, will allow the HSM to remain functional, and thereby achieve improved clinical outcomes, tracking albuminuria as a sentinel. Albuminuria was selected because of its high prevalence in SCD and its relative ease of diagnosis and monitoring. The hypothesis may be evaluated in four phases: Phase 1 will determine the concentration of Hp needed to trigger the HSM as measured by induction of CD163 and IL-10 and the recovery of hemopexin. Phase 2 will investigate the half-life of HSM induction by analyzing the time-course of CD163 expression and IL-10 and hemopexin serum concentration. Phase 3 will determine patient eligibility for therapy, whether as treatment or prevention. Phase 4 will test the efficacy of Hp transfusions in a randomized control trial as measured by correction of albuminuria. Angiotensin converting enzyme inhibitors (ACEi) are currently the first-line treatment for SCD nephropathy, however hyperkalemia limits its use. Hydroxyurea, which has therapeutic value in many SCD adverse events, has yielded inconsistent effects on albuminuria. We are proposing the addition of an intervention more proximal in the hemolytic cascade. Boosting the exhausted Hb-scavenging capacity via Hp replacement therapy has the potential to modify multiple downstream clinical events. PMID- 26141636 TI - Integrated theory to unify status among schizophrenia and manic depressive illness. AB - Tryptophan hydroxylase 1 is primarily expressed in the gastrointestinal tract, and has been associated with both schizophrenia and depression. Although decreased serotonin activity has been reported in both depression and mania, it is important to investigate the interaction between serotonin and other neurotransmitter systems. There are competitive relationships between branched chain amino acids, and tryptophan and tyrosine that relate to physical activity, and between L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5 HTP), both highly dependent on intracellular tetrahydrobiopterin concentrations. Here, I propose a chaos theory for schizophrenia, mania, and depression using the competitive interaction between tryptophan and tyrosine with regard to the blood brain barrier and coenzyme tetrahydrobiopterin. Mania may be due to the initial conditions of physical hyperactivity and hypofunctional 5-HTP-producing cells inducing increased dopamine. Depression may be due to the initial conditions of physical hypoactivity and hypofunctional 5-HTP-producing cells inducing decreased serotonin. Psychomotor excitation may be due to the initial conditions of physical hyperactivity and hyperfunctional 5-HTP-producing cells inducing increased serotonin and substantially increased dopamine. The hallucinatory paranoid state may be due to the initial conditions of physical hypoactivity and hyperfunctional 5-HTP-producing cells inducing increased serotonin and dopamine. PMID- 26141637 TI - Plausible etiology of brain dysconnectivity in autism - Review and prospectus. AB - This report summarizes recent findings related to the neuropathology of autism. Combining the relevant observations assessed here, a comprehensive, coherent hypothesis explaining the etiology of juvenile autism may be deduced. This proposed mechanism describes a process initiated by insulin-like growth factor deficiency, resulting in brain dysconnectivity as central to the behavioral manifestations of this disease. PMID- 26141638 TI - Common pathophysiology affecting diabetic retinopathy and Parkinson's disease. AB - Diabetic retinopathy (DR) is the leading cause of irreversible vision loss in adults. Parkinson's disease (PD) is a chronic progressive neurodegenerative movement disorder characterized by progressive loss of dopaminergic neurons in substantia nigra of midbrain. Evidences suggest that diabetic patients tend to show higher incidence of PD, advocating a shared mechanism between both the diseases. Interestingly, disruption of the dopaminergic system, which is an important causative factor in PD, has also been observed in DR. It is reported that retinal dopamine and tyrosine hydroxylase protein levels are downregulated, and dopaminergic amacrine cells appear to be degenerating in the animal models of DR. Further, injecting the diabetic mice with dopamine-restoring or dopamine activating drugs already used to treat PD can restore dopamine levels and significantly improve diabetes-associated visual dysfunction in the early stage. Conversely, drugs already in use for insulin resistance also show protective effects in PD. Furthermore, alpha-Synuclein pathology of PD can be induced solely by high glucose in diabetic animal models. In conclusion, these findings establish an important role of dopamine deficiency as a common contributing factor in DR and PD. The changes in the ocular of diabetes involve dopamine metabolism disturbance, mimicking PD at the molecular level. Consequently, we could consider DR as at least partially the PD like molecular pathology in the eye. Importantly, indicating that dopamine decrease may play a role in DR will lead to a better understanding of the high rate of comorbidity reported between diabetes and PD, and reveal new therapeutic avenues for DR and other disorders that involve dopamine deficiency. PMID- 26141639 TI - Might a conscience clause be used for non-moral or prejudiced reasons? PMID- 26141641 TI - Self-organization and advective transport in the cell polarity formation for asymmetric cell division. AB - Anterior-Posterior (AP) polarity formation of cell membrane proteins plays a crucial role in determining cell asymmetry, which depends not only on the several genetic process but also biochemical and biophysical interactions. The mechanism of AP formation of Caenorhabditis elegans embryo is characterized into the three processes: (i) membrane association and dissociation of posterior and anterior proteins, (ii) diffusion into the membrane and cytosol, and (iii) active cortical and cytoplasmic flows induced by the contraction of the acto-myosin cortex. We explored the mechanism of symmetry breaking and AP polarity formation using self recruitment model of posterior proteins. We found that the AP polarity pattern is established over wide range in the total mass of polarity proteins and the diffusion ratio in the cytosol to the membrane. We also showed that the advective transport in both membrane and cytosol during the establishment phase affects optimal time interval of establishment and positioning of the posterior domain, and plays a role to increase the robustness in the AP polarity formation by reducing the number of posterior domains for the sensitivity of initial conditions. We also demonstrated that a proper ratio of the total mass to cell size robustly regulate the length scale of the posterior domain. PMID- 26141640 TI - Development of behavioral parameters and ERPs in a novel-target visual detection paradigm in children, adolescents and young adults. AB - BACKGROUND: The present study analyzes the development of ERPs related to the process of selecting targets based on their novelty. METHODS: One hundred and sixty-seven subjects from 6 to 26 years old were recorded with 30 electrodes during a visual target novelty paradigm. RESULTS: Behavioral results showed good performance in children that improved with age: a decrease in RTs and errors and an increase in the d' sensitivity parameter with age were obtained. In addition, the C response bias parameter evolved from a conservative to a neutral bias with age. Fronto-polar Selection Positivity (FSP) was statistically significant in all the age groups when standards and targets were compared. There was a statistically significant difference in the posterior Selection Negativity (SN) between the target and standard conditions in all age groups. The P3a component obtained was statistically significant in the emergent adult (18-21 years) and young adult (22-26 years) groups. The modulation of the P3b component by novel targets was statistically significant in all the age groups, but it decreased in amplitude with age. Peak latencies of the FSP and P3b components decreased with age. CONCLUSIONS: The results reveal differences in the ERP indexes for the cognitive evaluation of the stimuli presented, depending on the age of the subjects. The ability of the target condition to induce the modulation of the studied components would depend on the posterior-anterior gradient of cortex maturation and on the gradient of maturation of the low to higher order association areas. PMID- 26141642 TI - A phenomenological model of myelinated nerve with a dynamic threshold. AB - To evaluate coding strategies for cochlear implants a model of the human cochlear nerve is required. Nerve models based on voltage-clamp experiments, such as the Frankenhaeuser-Huxley model of myelinated nerve, can have over forty parameters and are not amenable for fitting to physiological data from a different animal or type of nerve. Phenomenological nerve models, such as leaky integrate-and-fire (LIF) models, have fewer parameters but have not been validated with a wide range of stimuli. In the absence of substantial cochlear nerve data, we have used data from a toad sciatic nerve for validation (50 Hz to 2 kHz with levels up to 20 dB above threshold). We show that the standard LIF model with fixed refractory properties and a single set of parameters cannot adequately predict the toad rate level functions. Given the deficiency of this standard model, we have abstracted the dynamics of the sodium inactivation variable in the Frankenhaeuser-Huxley model to develop a phenomenological LIF model with a dynamic threshold. This nine parameter model predicts the physiological rate-level functions much more accurately than the standard LIF model. Because of the low number of parameters, we expect to be able to optimize the model parameters so that the model is more appropriate for cochlear implant simulations. PMID- 26141643 TI - Reconstruction of muscle fascicle architecture from iodine-enhanced microCT images: A combined texture mapping and streamline approach. AB - Skeletal muscle models are used to investigate motion and force generation in both biological and bioengineering research. Yet, they often lack a realistic representation of the muscle's internal architecture which is primarily composed of muscle fibre bundles, known as fascicles. Recently, it has been shown that fascicles can be resolved with micro-computed tomography (uCT) following staining of the muscle tissue with iodine potassium iodide (I2KI). Here, we present the reconstruction of the fascicular spatial arrangement and geometry of the superficial masseter muscle of a dog based on a combination of pattern recognition and streamline computation. A cadaveric head of a dog was incubated in I2KI and uCT-scanned. Following segmentation of the masseter muscle a statistical pattern recognition algorithm was applied to create a vector field of fascicle directions. Streamlines were then used to transform the vector field into a realistic muscle fascicle representation. The lengths of the reconstructed fascicles and the pennation angles in two planes (frontal and sagittal) were extracted and compared against a tracked fascicle field obtained through cadaver dissection. Both fascicle lengths and angles were found to vary substantially within the muscle confirming the complex and heterogeneous nature of skeletal muscle described by previous studies. While there were significant differences in the pennation angle between the experimentally derived and uCT-reconstructed data, there was congruence in the fascicle lengths. We conclude that the presented approach allows for embedding realistic fascicle information into finite element models of skeletal muscles to better understand the functioning of the musculoskeletal system. PMID- 26141644 TI - Evolution of fairness in the dictator game by multilevel selection. AB - The most perplexing experimental results on fairness come from the dictator game where one of two players, the dictator, decides how to divide a resource with an anonymous player. The dictator, acting self-interestedly, should offer nothing to the anonymous second player, but in experimental studies, dictators offer much more than nothing. We developed a multilevel selection model to explain why people offer more than nothing in the dictator game. We show that fairness can evolve when population structure emerges from the aggregation and limited dispersal of offspring. We begin with an analytical model that shows how fair behavior can benefit groups by minimizing within-group variance in resources and thereby increasing group fitness. To investigate the generality of this result, we developed an agent-based model with agents that have no information about other agents. We allowed agents to aggregate into groups and evolve different levels of fairness by playing the dictator game for resources to reproduce. This allowed multilevel selection to emerge from the spatiotemporal properties of individual agents. We found that the population structure that emerged under low population densities was most conducive to the evolution of fairness, which is consistent with group selection as a major evolutionary force. We also found that fairness only evolves if resources are not too scarce relative to the lifespan of agents. We conclude that the evolution of fairness could evolve under multilevel selection. Thus, our model provides a novel explanation for the results of dictator game experiments, in which participants often fairly split a resource rather than keeping it all for themselves. PMID- 26141645 TI - Using weighted features to predict recombination hotspots in Saccharomyces cerevisiae. AB - Characterization and accurate prediction of recombination hotspots and coldspots have crucial implications for the mechanism of recombination. Several models have predicted recombination hot/cold spots successfully, but there is still much room for improvement. We present a novel classifier in which k-mer frequency, physical and thermodynamic properties of DNA sequences are incorporated in the form of weighted features. Applying the classifier to recombination hot/cold ORFs in Saccharomyces cerevisiae, we achieved an accuracy of 90%, which is ~5% higher than existing methods, such as iRSpot-PseDNC, IDQD and Random Forest. The model also predicted non-ORF recombination hot/cold spots sequences in S. cerevisiae with high accuracy. A broad applicability of the model in the field of classification is expected. PMID- 26141646 TI - Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis. AB - BACKGROUND: Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO. METHODS: RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h and cytotoxicity was measured using a CCK-8 assay. Then, xenograft Balb/c nude mice were injected with RKO cells and subsequently orally administered with ethanol extract of Cordyceps militaris every day for 3 weeks to examine the inhibitory effect on tumor growth. Lastly, the effect of Cordyceps militaris on cell cycle as well as apoptosis was measured using flow cytometry. Also, the expression of p53, caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bax, Bak, and Bad were detected using western blot assay. RESULTS: RKO cells were highly susceptible to the ethanol extract of Cordyceps militaris (CME) and the growth of RKO cells-derived tumor was significantly delayed by the treatment of Cordyceps militaris. Cordyceps militaris induced cell cycle arrest in G2/M phase (untreated; 20.5 %, CME 100 MUg/ml; 61.67 %, CME 300 MUg/ml; 66.33 %) and increased early apoptosis (untreated; 1.01 %, CME 100 MUg/ml; 8.48 %, CME 300 MUg/ml; 18.07 %). The expression of p53, cleaved caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bak, and Bad were upregulated by the treatment of Cordyceps militaris. CONCLUSION: Ethanol extract of Cordyceps militaris was highly cytotoxic to human colorectal carcinoma RKO cells and inhibited the growth of tumor in xenograft model. The anti-tumor effect of Cordyceps militaris was associated with an induction of cell cycle arrest and mitochondrial-mediated apoptosis. PMID- 26141647 TI - RECK Gene Polymorphism is Associated with Susceptibility and Prognosis of Wilms' Tumor in Chinese Children. AB - BACKGROUND: Wilms' tumor (WT) is the most common malignant renal tumor in children. Previous studies suggested the reversion-inducing, cysteine-rich protein with Kazal motifs (RECK) down-regulation might have a role in numerous human cancers. The current study was done to investigate the associations of RECK single-nucleotide polymorphisms (SNPs) with the WT susceptibility in Chinese children. MATERIAL AND METHODS: We analyzed 2 SNPs (rs10972727 and rs11788747) in a total of 97 WT children and 194 healthy matched controls (1:2 ratio) by real time PCR and PCR-RFLP genotyping analysis. RESULTS: We found that the G allele of rs11788747 in the RECK gene was significantly associated with WT in Chinese children (OR=0.7, 95% CI: 0.45-0.99; P=0.042); as with another SNP rs10972727, however, no statistically significant difference was detected. Further analysis showed there was also a statistically significant difference in genotype frequencies between terminal tumor stage (P=0.026) and metastatic groups (P=0.002). CONCLUSIONS: The present data indicate that there is a significant association between mutant G of rs11788747 in RECK and WT risk. G carriers with advanced tumor stage or with metastasis might have an increased risk of WT. PMID- 26141648 TI - Mechanical properties of resin-ceramic CAD/CAM restorative materials. AB - STATEMENT OF PROBLEM: The recent development of polymer-based computer-aided design and computer-aided manufactured (CAD/CAM) milling blocks and the limited availability of independent studies on these materials make it pertinent to evaluate their properties and identify potential strengths and limitations. PURPOSE: The purpose of this in vitro study was to determine and compare mechanical properties (flexural strength, flexural modulus, modulus of resilience) and compare the margin edge quality of recently introduced polymer based CAD/CAM materials with some of their commercially available composite resin and ceramic counterparts. MATERIAL AND METHODS: The materials studied were Lava Ultimate Restorative (LVU; 3M ESPE), Enamic (ENA; Vita Zahnfabrik), Cerasmart (CES; GC Dental Products), IPS Empress CAD (EMP; Ivoclar Vivadent AG), Vitablocs Mark II (VM2; Vita Zahnfabrik), and Paradigm MZ100 Block (MZ1; 3M ESPE). Polished 4*1*13.5 mm bars (n=25) were prepared from standard-sized milling blocks of each tested material. The bars were subjected to a 3-point flexural test on a 10-mm span with a crosshead speed of 0.5 mm/min. In addition, 42 conventional monolithic crowns (7 per material) were milled. Margin edge quality was observed by means of macrophotography and optical microscopy, providing a qualitative visual assessment and a measurement of existing roughness. The results were analyzed by ANOVA followed by the Tukey HSD test (alpha=.05). RESULTS: The mean flexural strength of the tested materials ranged from 105 +/-9 MPa (VM2) to 219 +/-20 MPa (CES). The mean flexural modulus ranged from 8 +/-0.25 GPa (CES) to 32 +/-1.9 GPa (EMP). The mean modulus of resilience ranged from 0.21 +/-0.02 MPa (VM2) to 3.07 +/-0.45 MPa (CES). The qualitative assessment of margin edge roughness revealed visible differences among the tested materials, with mean roughness measurements ranging from 60 +/-16 MUm (CES) to 190 +/-15 MUm (EMP). The material factor had a significant effect on the mean flexural strength (P<.001), flexural modulus (P<.001), modulus of resilience (P<.001), and margin edge roughness (P<.001) of the tested specimens. CONCLUSIONS: The new-generation polymer-based materials tested in this study exhibited significantly higher flexural strength and modulus of resilience, along with lower flexural modulus values compared with the tested ceramic or hybrid materials. Crowns milled from the new resin-based blocks seemed to exhibit visibly smoother margins compared with the ceramic materials studied. PMID- 26141650 TI - Erratum. PMID- 26141649 TI - The reduced expression of proximal tubular transporters in acquired Fanconi syndrome with kappa light chain deposition. AB - In a case of acquired Fanconi syndrome associated with smoldering myeloma, we confirmed the deposition of protease-resistant kappa light chain proteins in a proximal tubular injury and found the decreased expression of apical tubular transporters including sodium glucose co-transporter, sodium phosphate co transporter, uric acid transporter 1, and a decrease of Na(+)/K(+)-ATPase in the basolateral membrane. The protease-resistant kappa light chain has a pathological role in the expression of tubular transporters in the proximal tubule and causes Fanconi syndrome associated with smoldering myeloma. PMID- 26141651 TI - Immune-microbiota interactions in health and disease. AB - Recent studies have revealed that the intestinal microbiota plays an important role in host physiology and pathophysiology in health and disease. One of the major mechanisms by which the gut microbiota influences the host is through its interactions with and effects on the host immune system. In this review, we discuss the reciprocal interactions between the host immune system and the gut microbiota, with a particular focus on individual microbes that impact the host through dramatic and specific interactions with the adaptive immune system. We highlight the idea that the presence or absence of specific immunologically important members of the microbiota can determine disease susceptibility and propose that the identification and characterization of these bacteria in humans will eventually allow us to elucidate the role of microbiota composition in human disease. PMID- 26141652 TI - Physical activity, sedentary behavior and all-cause mortality among blacks and whites with diabetes. AB - PURPOSE: The study objective was to examine the role of physical activity (PA) and sedentary time (ST) on mortality risk among a population of low-income adults with diabetes. METHODS: Black (n = 11,137) and white (n = 4508) men and women with diabetes from the Southern Community Cohort Study self-reported total PA levels and total ST. Participants were categorized into quartiles of total PA and total ST. Hazard ratios (HRs) and 95% confidence intervals (CIs) for subsequent mortality risk were estimated from Cox proportional hazards analysis with adjustment for potential confounders. RESULTS: During follow-up, 2370 participants died. The multivariable risk of mortality was lower among participants in the highest quartile of PA compared with those in the lowest quartile (HR, 0.64; 95% CI: 0.57-0.73). Mortality risk was significantly increased among participants in the highest compared with the lowest quartile of ST after adjusting for PA (HR, 1.21; 95% CI: 1.08-1.37). Across sex and race groups, similar trends of decreasing mortality with rising PA and increasing mortality with rising ST were observed. CONCLUSIONS: Although causality cannot be established from these observational data, the current findings suggest that increasing PA and decreasing ST may help extend survival among individuals with diabetes irrespective of race and sex. PMID- 26141653 TI - A new diagnostic kit, ODK-1201, for the quantitation of low major BCR-ABL mRNA level in chronic myeloid leukemia: correlation of quantitation with major BCR-ABL mRNA kits. AB - The current first-line therapy of chronic myeloid leukemia (CML) is based on tyrosine kinase inhibitors. Diagnostic kits that are capable of identifying at least a 4.5 log reduction in the international scale % BCR-ABL/ABL (IS % BCR ABL/ABL) are needed for use in the clinical evaluation of deeper molecular response to treatment and to determine the timing of dose selection or treatment interruption during the course of treatment. In this study, we evaluated the performance of a new diagnostic kit, ODK-1201, designed to be capable of performing reverse transcription and quantitative PCR in a single tube for the quantitation of major BCR-ABL mRNA. The kit demonstrated excellent assay performance (limit of detection 0.0007 %) and a broader detection range of BCR ABL mRNA in peripheral blood compared to a commercially available kit for CML (Amp-CML). ODK-1201 was also shown to be as sensitive as Ipsogen and Molecular MD kits in the same assay. Results obtained in this study indicate evidences that ODK-1201 was capable of identifying at least a 4.5 log reduction in the IS % BCR ABL/ABL. PMID- 26141654 TI - Temporal trends in fetal mortality at and beyond term and induction of labor in Germany 2005-2012: data from German routine perinatal monitoring. AB - PURPOSE: While a variety of factors may play a role in fetal and neonatal deaths, postmaturity as a cause of stillbirth remains a topic of debate. It still is unclear, whether induction of labor at a particular gestational age may prevent fetal deaths. METHODS: A multidisciplinary working group was granted access to the most recent set of relevant German routine perinatal data, comprising all 5,291,011 hospital births from 2005 to 2012. We analyzed correlations in rates of induction of labor (IOL), perinatal mortality (in particular stillbirths) at different gestational ages, and fetal morbidity. Correlations were tested with Pearson's product-moment analysis (alpha = 5 %). All computations were performed with SPSS version 22. RESULTS: Induction rates rose significantly from 16.5 to 21.9 % (r = 0.98; p < 0.001). There were no significant changes in stillbirth rates (0.28-0.35 per 100 births; r = 0.045; p = 0.806). Stillbirth rates 2009 2012 remained stable in all gestational age groups irrespective of induction. Fetal morbidity (one or more ICD-10 codes) rose significantly during 2005-2012. This was true for both children with (from 33 to 37 %, r = 0.784, p < 0.001) and without (from 25 to 31 %, (r = 0.920, p < 0.001) IOL. CONCLUSIONS: An increase in IOL at term is not associated with a decline in perinatal mortality. Perinatal morbidity increased with and without induction of labor. PMID- 26141655 TI - Qualitative Evaluation of Medical Information Processing Needs of 60 Women Choosing Ovarian Cancer Surveillance or Prophylactic Oophorectomy. AB - Thirty women who had prophylactic oophorectomy (PO) and thirty women undergoing ovarian cancer surveillance (OCS) completed a one-time in-depth telephone interview exploring information gathering and decision-making processes. There were close similarities between groups, including age, race, marital status, education, menopausal status, number undergoing genetic testing for BRCA mutations, and number of prophylactic mastectomies. The majority of participants indicated overall satisfaction with their final decision. However, many described the information gathering process as frustrating and anxiety provoking. Participants in both groups expressed a need to process medical information within the context of individual psychosocial needs and personal perceptions and experiences. There were recurrent themes with regard to informational and psychosocial needs and personal perceptions and experiences that impacted decision-making process for these women. The present paper is a companion paper to Swisher et al. (J Repr Med 2001, 46:87-94) with the focus of this paper to illustrate the medical informational processing needs identified by this group of women. PMID- 26141657 TI - Instructions to Contributors. PMID- 26141658 TI - Erratum. PMID- 26141656 TI - Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors. AB - The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations. PMID- 26141659 TI - Proteomic and histopathological response in the gills of Poecilia reticulata exposed to glyphosate-based herbicide. AB - Glyphosate-based herbicides (GBH) are one of the most used herbicide nowadays, whilst there is growing concern over their impact on aquatic environment. Since data about the early proteomic response and toxic mechanisms of GBH in fish is very limited, the aim of this study was to investigate the early toxicity of GBH in the gills of guppies Poecilia reticulata using a proteomic approach associated with histopathological index. Median lethal concentration (LC50,96 h) was determined and LC50,96h values of guppies exposed to GBH were 3.6 +/- 0.4 mg GLIL(-1). Using two-dimensional gel electrophoresis associated with mass spectrometry, 14 proteins regulated by GBH were identified, which are involved in different cell processes, as energy metabolism, regulation and maintenance of cytoskeleton, nucleic acid metabolism and stress response. Guppies exposed to GBH at 1.82 mg GLIL(-1) showed time-dependent histopathological response in different epithelial and muscle cell types. The histopathological indexes indicate that GBH cause regressive, vascular and progressive disorders in the gills of guppies. This study helped to unravel the molecular and tissue mechanisms associated with GBH toxicity, which are potential biomarkers for biomonitoring water pollution by herbicides. PMID- 26141660 TI - Concentrating nanoparticles in environmental monitoring. AB - There are significant challenges in assessing the toxicity of nanoparticles in the environment in which effective methods for detection are crucial. An inexpensive method that uses superhydrophobic well with an evaporating droplet followed by a simple squeeze flow is described here and found to provide practical high nanoparticle collection from samples for detection. The process could be hastened by placing a radiant heater close to the droplet if temperature rises in the sample can be tolerated. PMID- 26141661 TI - How will things be the next time? Self in the construction of future events among school-aged children. AB - This study examined among school-aged children the role of the self in perceived valence changes from the past to the future. Nine- to 11-year-old children (N=57) recalled positive and negative personal events of various situations and imagined a future personal event involving the same situation following each recall. Children's self-knowledge was assessed in terms of self-concepts for past, present, and future selves, and self-evaluations for social and cognitive competences. Children who viewed their future selves more positively and those who evaluated their cognitive competence more positively anticipated greater upward (positive) changes and smaller downward (negative) changes in their future academic performance. Children who evaluated their social competence more positively anticipated greater upward changes in their future peer relations. Furthermore, children who anticipated greater upward changes and smaller downward changes in their personal futures exhibited greater well-being. These findings shed new light on the role of self in mental time travel. PMID- 26141662 TI - The ecology of self-monitoring effects on memory of verbal productions: Does speaking to someone make a difference? AB - Experiments involving verbal self-monitoring show that memory for spoken words varies with types of sensory feedback: memory is better when words are spoken aloud than when they are lip-synched or covertly produced. Such effects can be explained by the Central Monitoring Theory (CMT) via a process that matches a forward model reflecting expected sensory effects of practiced forms and sensory information during speech. But CMT oversees factors of shared attention as achieved by speaker-listener gaze, and implies that sensory feedback may not affect the learning of unpracticed forms (non-words). These aspects of CMT were examined in two experiments of self-monitoring focusing on oro-sensory feedback. In Experiment 1 we show that varying feedback creates differential effects on memory for spoken words and that speaker-listener gaze alters these effects. Using non-words, Experiment 2 shows the absence of differential feedback effects. The results confirm CMT but suggest the need to refine the theory in terms of processes that mediate attention. PMID- 26141663 TI - [Evolution of the management of pediatric and adult medulloblastoma]. AB - Medulloblastoma are cerebellar tumours belonging to the group of primitive neuroectodermal tumours (PNET) and are the most common malignant brain tumours of childhood. These tumours are rare and heterogeneous, requiring some multicentric prospective studies and multidisciplinary care. The classical therapeutic approaches are based on clinical, radiological and surgical data. They involve surgery, radiation therapy and chemotherapy. Some histological features were added to characterize risk. More recently, molecular knowledge has allowed to devise risk-adapted strategies and helped to define groups with good outcome and reduce long-term sequelae, improve the prognostic of high-risk medulloblastoma and develop new therapeutic tools. PMID- 26141664 TI - Revisiting disease genes based on whole-exome sequencing in consanguineous populations. AB - Assigning a causal role for genes in disease states is one of the most significant medical applications of human genetics research. The requirement for at least two different pathogenic alleles in the same gene in individuals with a similar phenotype to assign a causal link has not always been fully adhered to, and we now know that even two alleles may not necessarily constitute sufficient evidence. Autozygosity is a rich source of natural "knockout" events by virtue of rendering ancestral loss-of-function (LOF) variants homozygous. In this study, we exploit this phenomenon by examining 523 exomes enriched for autozygosity to call into question previously published disease links for several genes based on the identification of confirmed homozygous LOF variants in the absence of the purported diseases. This study highlights an additional advantage of consanguineous populations in the quest to improve the medical annotation of the human genome. PMID- 26141665 TI - Biomechanical analyses of prolonged handwriting in subjects with and without perceived discomfort. AB - Since wrist-joint position affects finger muscle length and grip strength, we studied its biomechanical relevance in prolonged handwriting. We recruited participants from young adults, aged 18-24, and separated them into control (n=22) and in-pain (n=18) groups, based whether or not they experience pain while handwriting. The participants then performed a writing task for 30 min on a computerized system which measured their wrist-joint angle and documented their handwriting kinematics. The in-pain group perceived more soreness and had a less extended wrist joint, longer on-paper time, and slower stroke velocity compared to control group. There was no significant difference in handwriting speed and quality between the two groups. The wrist extension angle significantly correlated with perceived soreness. Ergonomic and biomechanical analyses provide important information about the handwriting process. Knowledge of pen tip movement kinematics and wrist-joint position can help occupational therapists plan treatment for individuals with handwriting induced pain. PMID- 26141667 TI - Characterization and optimization of cathodic conditions for H2O2 synthesis in microbial electrochemical cells. AB - Cathode potential and O2 supply methods were investigated to improve H2O2 synthesis in an electrochemical cell, and optimal cathode conditions were applied for microbial electrochemical cells (MECs). Using aqueous O2 for the cathode significantly improved current density, but H2O2 conversion efficiency was negligible at 0.3-12%. Current density decreased for passive O2 diffusion to the cathode, but H2O2 conversion efficiency increased by 65%. An MEC equipped with a gas diffusion cathode was operated with acetate medium and domestic wastewater, which presented relatively high H2O2 conversion efficiency from 36% to 47%, although cathode overpotential was fluctuated. Due to different current densities, the maximum H2O2 production rate was 141 mg H2O2/L-h in the MEC fed with acetate medium, but it became low at 6 mg H2O2/L-h in the MEC fed with the wastewater. Our study clearly indicates that improving anodic current density and mitigating membrane fouling would be key parameters for large-scale H2O2-MECs. PMID- 26141666 TI - A critical review on characterization strategies of organic matter for wastewater and water treatment processes. AB - The presence of organic matter (OM) in raw wastewater, treated wastewater effluents, and natural water samples has been known to cause many problems in wastewater treatment and water reclamation processes, such as treatability, membrane fouling, and the formation of potentially toxic by-products during wastewater treatment. This paper summarizes the current knowledge on the methods for characterization and quantification of OM in water samples in relation to wastewater and water treatment processes including: (i) characterization based on the biodegradability; (ii) characterization based on particle size distribution; (iii) fractionation based on the hydrophilic/hydrophobic properties; (iv) characterization based on the molecular weight (MW) size distribution; and (v) characterization based on fluorescence excitation emission matrix. In addition, the advantages, disadvantages and applications of these methods are discussed in detail. The establishment of correlations among biodegradability, hydrophobic/hydrophilic fractions, MW size distribution of OM, membrane fouling and formation of toxic by-products potential is highly recommended for further studies. PMID- 26141668 TI - Separators used in microbial electrochemical technologies: Current status and future prospects. AB - Microbial electrochemical technologies (METs) are emerging green processes producing useful products from renewable sources without causing environmental pollution and treating wastes. The separator, an important part of METs that greatly affects the latter's performance, is commonly made of Nafion proton exchange membrane (PEM). However, many problems have been identified associated with the Nafion PEM such as high cost of membrane, significant oxygen and substrate crossovers, and transport of cations other than protons protons and biofouling. A variety of materials have been offered as alternative separators such as ion-exchange membranes, salt bridges, glass fibers, composite membranes and porous materials. It has been claimed that low cost porous materials perform better than PEM. These include J-cloth, nylon filter, glass fiber mat, non-woven cloth, earthen pot and ceramics that enable non-ion selective charge transfer. This paper provides an up-to-date review on porous separators and plots directions for future studies. PMID- 26141669 TI - Sorption of lead by Salisbury biochar produced from British broadleaf hardwood. AB - In this study, the physicochemical properties of Salisbury biochar produced from British broadleaf hardwood and its adsorption characteristics towards lead were investigated. The biochar particle size has a significant effect on its BET surface area, cation exchange capacity and sorption of lead. The kinetics data were well fitted by the Pseudo second order model. The increase of biochar dosage increased the percentage of lead removal in solutions. The increase of initial solution pH increased the percentage of lead removal across the pH range of 2-10. The calculated maximum adsorption capacities of lead by Langmuir model were 47.66 and 30.04 mg/g for 0.15 mm and 2 mm samples. The adsorption capacities of different metals decreased in the order of lead > nickel > copper > zinc calculated in mmol/g. This study suggests a great potential of biochars derived from British broadleaf hardwood to be applied in soil remediation. PMID- 26141670 TI - Graphitic biochar as a cathode electrocatalyst support for microbial fuel cells. AB - Graphitic biochar (BC) was generated using high temperature gasification and alkaline post-treatment (BCw) of wood-based biomass. The BCw was evaluated as a manganese oxide electrocatalytic support (MnO/BCw) and microbial fuel cell (MFC) air cathode. Nano-structured MnO2 crystals were successfully immobilized on biomass-based graphitic sheets and characterized using physical, chemical, and electrochemical analyses. Cyclic voltammetry of MnO/BCw/Nafion inks showed electrochemical features typical of beta-MnO2 with a current density of 0.9 mA cm(-2). BC showed satisfactory maximum power densities of 146.7 mW m(-2) (BCw) and 187.8 W m(-2) (MnO/BCw), compared with Vulcan Carbon (VC) (156.8 mW m(-2)) and manganese oxide VC composites (MnO/VC) (606.1 mW m(-2)). These materials were also tested as oxygen reduction reaction (ORR) catalysts for single chamber MFCs inoculated with anaerobic sludge. Our results demonstrate that BC can serve as an effective, low cost, and scalable material for MFC application. PMID- 26141671 TI - Metformin ameliorates the proinflammatory state in patients with carotid artery atherosclerosis through sirtuin 1 induction. AB - Metformin is a widely used classic antidiabetic drug. However, its clinical pharmacologic mechanism remains poorly understood. In the present study, we investigated the anti-inflammatory effects of metformin on circulating peripheral blood mononuclear cells (MNCs) of patients with carotid artery atherosclerosis (AS). A total of 42 patients with carotid artery AS were randomly assigned to metformin (500 mg twice a day; Met; n = 21) or placebo control (Con; n = 21) groups. After 12 weeks of treatment, plasma concentrations of high-sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) significantly decreased in the Met group compared with the Con group. In addition, treatment with metformin significantly reduced the expression of IL 6 and TNF-alpha at the messenger RNA level and attenuated nuclear factor kappa B (NF-kappaB) DNA binding activity in MNCs. Intriguingly, metformin did not alter the expression of NF-kappaB p65 subunit, but markedly inhibited its acetylation. Furthermore, metformin significantly induced sirtuin 1 (SIRT1) expression in MNCs. Moreover, we found that metformin treatment dramatically induced SIRT1 expression, blocked p65 acetylation, and inhibited NF-kappaB activity and the expression of inflammatory factors in MNCs in vitro. We conclude that metformin has a novel direct protective role to ameliorate the proinflammatory response through SIRT1 induction, p65 acetylation reduction, NF-kappaB inactivation, and inflammatory inhibition in peripheral blood MNCs of patients with carotid artery AS. PMID- 26141672 TI - Commentary on: The Role of Microfat Grafting in Facial Contouring. PMID- 26141673 TI - Commentary on: transaxillary endoscopic breast augmentation with shaped gel implants. PMID- 26141674 TI - The Impact of Protein Nutritional Supplementation for Massive Weight Loss Patients Undergoing Abdominoplasty. AB - BACKGROUND: As more patients undergo bariatric surgery to assist with weight loss, the demand for post-bariatric body contouring surgery, to address both functional and aesthetic concerns, is increasing. However, high wound healing complication rates remain a significant problem for these patients. One theory is that chronic malnourishment and hypoproteinemia may contribute significantly to these wound healing complications. OBJECTIVE: The purpose of this study was to determine the effect of pretreatment protein nutritional supplementation on wound healing in post-bariatric surgery massive weight loss patients undergoing abdominoplasty. Our hypothesis was that protein supplementation would decrease wound healing complications. METHODS: A retrospective review was performed of 23 post-bariatric surgery patients undergoing abdominoplasty who received pretreatment protein nutritional supplementation. This group was compared with a historical control group of 23 post-bariatric surgery patients who underwent abdominoplasty in the period immediately before the implementation of the protein supplementation protocol. Patient demographics and procedural characteristics were similar for the two groups. RESULTS: Forty-six patients were identified who had undergone abdominoplasty, half of whom were prescribed the protein supplementation protocol. Overall wound healing complication rates were significantly lower in the protein-supplemented group (0.0% vs. 21.8%, p = 0.04). There was no significant difference between the protein supplementation and historical control groups in regards to total complication rate. CONCLUSIONS: Pretreatment protein supplementation is a simple intervention that can significantly decrease wound healing complications in post-bariatric surgery massive weight loss patients undergoing abdominoplasty. LEVEL OF EVIDENCE 4: Therapeutic. PMID- 26141675 TI - Abstracts from the Nineteenth Annual Education Conference of the National Society of Genetic Counselors (Savannah, Georgia, November 2000). PMID- 26141676 TI - Near-infrared spectroscopy assessed cerebral oxygenation during open abdominal aortic aneurysm repair: relation to end-tidal CO2 tension. AB - During open abdominal aortic aneurism (AAA) repair cerebral blood flow is challenged. Clamping of the aorta may lead to unintended hyperventilation as metabolism is reduced by perfusion of a smaller part of the body and reperfusion of the aorta releases vasodilatory substances including CO2. We intend to adjust ventilation according end-tidal CO2 tension (EtCO2) and here evaluated to what extent that strategy maintains frontal lobe oxygenation (ScO2) as determined by near infrared spectroscopy. For 44 patients [5 women, aged 70 (48-83) years] ScO2, mean arterial pressure (MAP), EtCO2, and ventilation were obtained retrospectively from the anesthetic charts. By clamping the aorta, ScO2 and EtCO2 were kept stable by reducing ventilation (median, -0.8 l min(-1); interquartile range, -1.1 to -0.4; P < 0.001). During reperfusion of the aorta a reduction in MAP by 8 mmHg (-15 to -1; P < 0.001) did not prevent an increase in ScO2 by 2 % ( 1 to 4; P < 0.001) as EtCO2 increased 0.5 kPa (0.1-1.0; P < 0.001) despite an increase in ventilation by 1.8 l min(-1) (0.9-2.7; P < 0.001). Changes in ScO2 related to those in EtCO2 (r = 0.41; P = 0.0001) and cerebral deoxygenation (-15 %) was noted in three patients while cerebral hyperoxygenation (+15 %) manifests in one patient. Thus changes in ScO2 were kept within acceptable limits (+/-15 %) in 91 % of the patients. For the majority of the patients undergoing AAA repair ScO2 was kept within reasonable limits by reducing ventilation by approximately 1 l min(-1) upon clamping of the aorta and increasing ventilation by approximately 2 l min(-1) when the lower body is reperfused. PMID- 26141677 TI - Computational prediction and biochemical characterization of novel RNA aptamers to Rift Valley fever virus nucleocapsid protein. AB - Rift Valley fever virus (RVFV) is a potent human and livestock pathogen endemic to sub-Saharan Africa and the Arabian Peninsula that has potential to spread to other parts of the world. Although there is no proven effective and safe treatment for RVFV infections, a potential therapeutic target is the virally encoded nucleocapsid protein (N). During the course of infection, N binds to viral RNA, and perturbation of this interaction can inhibit viral replication. To gain insight into how N recognizes viral RNA specifically, we designed an algorithm that uses a distance matrix and multidimensional scaling to compare the predicted secondary structures of known N-binding RNAs, or aptamers, that were isolated and characterized in previous in vitro evolution experiment. These aptamers did not exhibit overt sequence or predicted structure similarity, so we employed bioinformatic methods to propose novel aptamers based on analysis and clustering of secondary structures. We screened and scored the predicted secondary structures of novel randomly generated RNA sequences in silico and selected several of these putative N-binding RNAs whose secondary structures were similar to those of known N-binding RNAs. We found that overall the in silico generated RNA sequences bound well to N in vitro. Furthermore, introduction of these RNAs into cells prior to infection with RVFV inhibited viral replication in cell culture. This proof of concept study demonstrates how the predictive power of bioinformatics and the empirical power of biochemistry can be jointly harnessed to discover, synthesize, and test new RNA sequences that bind tightly to RVFV N protein. The approach would be easily generalizable to other applications. PMID- 26141678 TI - Cardiovascular risk with androgen deprivation therapy for prostate cancer: potential mechanisms. AB - Androgen deprivation therapy (ADT) is frequently used for the treatment of advanced prostate cancer. ADT is associated with numerous side effects related to its mode of action, namely the suppression of testosterone to castrate levels. Recently, several large retrospective studies have also reported an increased risk of diabetes and cardiovascular disease in men receiving ADT, although these risks have not been confirmed by prospective randomized trials. We review the literature to consider the risk of cardiovascular disease with different forms of ADT and examine in detail potential mechanisms by which any such risk could be mediated. Mechanisms discussed include the metabolic syndrome resulting from low testosterone level and the potential roles of testosterone flare, gonadotropin releasing hormone receptors outside the pituitary gland, and altered levels of follicle-stimulating hormone. Finally, the clinical implications for men prescribed ADT for the treatment of advanced prostate cancer are considered. PMID- 26141679 TI - Effect of Erythrodiol, A Natural Pentacyclic Triterpene from Olive Oil, on the Lipid Membrane Properties. AB - The effect of erythrodiol, a natural pentacyclic triterpene to which humans are exposed through nutrients, on the lipid membranes is studied using liposomes as a membrane model. Empty and erythrodiol-loaded liposomes were prepared by the reverse phase evaporation method followed by the extrusion and by the thin film hydration method. Liposomes were characterized in terms of size and zeta potential and were imaged by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The effect of erythrodiol on thermotropic behavior of DPPC bilayers is also examined by differential scanning calorimetry (DSC). The DSC thermograms suggested that erythrodiol interacted with the polar head groups of phospholipids and may produce a disruption of the ordering of the alkyl chains. The diffraction light scattering analysis showed that erythrodiol-loaded liposomes presented a decrease in the vesicle size when compared to blank liposomes. Images obtained by TEM confirmed the formation of unilamellar and spherical liposomes. AFM images showed spherical vesicles and single lipid bilayers. The latter were more abundant in the preparations containing erythrodiol than in the blank ones. Moreover, erythrodiol-loaded liposomes tended to rupture into single lipid bilayers during scanning. The study may provide a better understanding of pentacyclic triterpenes-membrane interaction. PMID- 26141680 TI - Combination of hyperuricemia and metabolic syndrome is an independent and powerful predictor for left ventricular hypertrophy in rural Chinese. AB - OBJECTIVES: To investigate the influence of MetS (metabolic syndrome) in combination with hyperuricemia on left ventricular hypertrophy (LVH) in residents in the rural area of Northeast China. METHODS: We performed a cross-sectional baseline data analysis of 11,170 subjects (mean age: 54+/-11years) recruited from the rural area of China. Anthropometric indicators were measured according to standard methods. MetS was defined by the ATP III modified criteria. Hyperuricemia was defined according to sex-specific serum uric acid levels (SUA): SUA>=7.0mg/dL for male and>=6.0mg/dL for female. Four groups were listed: normouricemia non-MetS, hyperuricemia non-MetS, MetS normouricemia and hyperuricemia MetS. RESULTS: Left ventricular mass index for height(2.7) (LVMH(2.7)) in female was significantly higher in hyperuricemia MetS group than that in normouricemia non-MetS (52.43+/-16.60 vs. 40.04+/-10.72g/m(2.7), P<0.001) group. Similar result was observed in men (48.93+/-13.17g/m(2.7) vs. 43.63+/ 11.90g/m(2.7), P<0.001). The result of multiple regression analysis indicated that hyperuricemia MetS group had higher risk of LVH than other three groups (OR: 3.427 for female, P<0.001, OR: 1.987 for male, P<0.001). Moreover, female subjects in MetS normouricemia group [OR (95% CI): 2.313 (1.991-2.686)] had greater risk of LVH than that in hyperuricemia non-MetS group [OR (95% CI): 1.917 (1.166-3.151)]. Hyperuricemia non-MetS was found to be significantly and independently associated with LVH in women, but not in men. CONCLUSION: Our study finds that the combination of hyperuricemia and MetS are independent and powerful predictor for LVH in rural area of Northeast Chinese. Women with MetS in combination with hyperuricemia have higher risk of LVH than men. It seems that MetS has greater effect on LVH than hyperuricemia does in women but not in men. PMID- 26141681 TI - Seasonal variation in diagnosis of invasive cutaneous melanoma in Eastern England and Scotland. AB - BACKGROUND: Worldwide, the incidence of cutaneous melanoma has been reported to be highest in the summer and lowest in the winter. Northern Irish data suggested seasonal variation for women only, especially those with thinner melanomas, sited on limbs. We interrogated two larger UK cancer registries for temporal differences in melanoma diagnosis and associated patient characteristics. METHODS: Melanomas diagnosed from 2006 to 2010 in the Eastern England and Scottish cancer registries (n=11,611) were analysed by month of diagnosis, patient demographics and melanoma characteristics, using descriptive and multivariate modelling methods. RESULTS: More patients with melanoma were diagnosed in the summer months (June 9.9%, July 9.7%, August 9.8%) than the winter months (December 7.2%, January 7.2%, February 7.1%) and this pattern was consistent in both regions. There was evidence that the seasonal patterns varied by sex (p=0.015), melanoma thickness (p=0.002), body site (p=0.006), and type (superficial spreading melanomas p=0.005). The seasonal variation was greatest for diagnosis of melanomas occurring on the limbs. CONCLUSION: This study has confirmed seasonal variation in melanoma diagnosis in Eastern England and Scotland across almost all population demographics and melanoma characteristics studied, with higher numbers diagnosed in the summer months, particularly on the limbs. Seasonal patterns in skin awareness and related help-seeking are likely to be implicated. Targeted patient interventions to increase sun awareness and encourage year-long skin inspection are warranted. PMID- 26141682 TI - Effectiveness of internet-supported cognitive behavioral and chronobiological interventions and effect moderation by insomnia subtype: study protocol of a randomized controlled trial. AB - BACKGROUND: DSM-V criteria for insomnia disorder are met by 6 to 10% of the adult population. Insomnia has severe consequences for health and society. One of the most common treatments provided by primary caregivers is pharmacological treatment, which is far from optimal and has not been recommended since a 2005 consensus report of the National Institutes of Health. The recommended treatment is Cognitive Behavioral Therapy for Insomnia. Effectiveness, however, is still limited. Only a few studies have evaluated the effectiveness of chronobiological treatments, including the timed application of bright light, physical activity and body warming. Another opportunity for optimization of treatment is based on the idea that the people suffering from insomnia most likely represent a heterogeneous mix of subtypes, with different underlying causes and expected treatment responses. The present study aims to evaluate the possibility for optimizing insomnia treatment along the principles of personalized and stratified medicine. It evaluates the following: 1. The relative effectiveness of internet supported cognitive behavioral therapy, bright light, physical activity and body warming; 2. Whether the effectiveness of internet-supported cognitive behavioral therapy for insomnia can be augmented by simultaneous or prior application of bright light, physical activity and body warming; and 3. Whether the effectiveness of the interventions and their combination are moderated by the insomnia subtype. METHODS/DESIGN: In a repeated measures, placebo-controlled, randomized clinical trial that included 160 people diagnosed with insomnia disorder, we are evaluating the relative effectiveness of 4 intervention weeks. Primary outcome is subjective sleep efficiency, quantified using a sleep diary. Secondary outcomes include other complaints of sleep and daytime functioning, health-related cost estimates and actigraphic objective sleep estimates. Compliance will be monitored both subjectively and objectively using activity, light and temperature sensors. Insomnia subtypes will be assessed using questionnaires. Mixed effect models will be used to evaluate intervention effects and moderation by insomnia subtype ratings. DISCUSSION: The current study addresses multiple opportunities to optimize and personalize treatment of insomnia disorder. TRIAL REGISTRATION: Netherlands National Trial Register NTR4010, 4 June 2013. PMID- 26141683 TI - STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer. AB - BACKGROUND: The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. METHODS/DESIGN: STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. DISCUSSION: The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. TRIAL REGISTRATION: STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013. STRATEGIC-1 is registered at EudraCT-No.: 2013-001928-19, 25 April, 2013. PMID- 26141684 TI - Midostaurin preferentially attenuates proliferation of triple-negative breast cancer cell lines through inhibition of Aurora kinase family. AB - BACKGROUND: Breast cancer is classified into three subtypes by the expression of biomarker receptors such as hormone receptors and human epidermal growth factor receptor 2. Triple-negative breast cancer (TNBC) expresses none of these receptors and has an aggressive phenotype with a poor prognosis, which is insensitive to the drugs that target the hormone receptors and human epidermal growth factor receptor 2. It is, thus, required to develop an effective therapeutic reagent to treat TNBC. RESULTS: The study using a panel of 19 breast cancer cell lines revealed that midostaurin, a multi-target protein kinase inhibitor, suppresses preferentially the growth of TNBC cells comparing with non TNBC cells. Clustering analysis of the drug activity data for the panel of cancer cell lines predicted that midostaurin shares the target with Aurora kinase inhibitors. Following studies indicated that midostaurin attenuates the phosphorylation reaction mediated by Aurora kinase in the cells and directly inhibits this protein kinase in vitro, and that this reagent induces apoptosis accompanying accumulation of 4N and 8N DNA cells in TNBC cells. CONCLUSION: Midostaurin suppresses the proliferation of TNBC cells among the breast cancer cell lines presumably through the inhibition of the Aurora kinase family. The precise study of midostaurin on cell growth will contribute to the development of the drug for the treatment of TNBC. PMID- 26141685 TI - One year of anaesthesia in France: A comprehensive survey based on the national medical information (PMSI) database. Part 1: In-hospital patients. AB - Anaesthesia has evolved in France since the last epidemiologic survey in 1996. The national database program for medical information systems (the PMSI) can be used to track specific knowledge concerning anaesthesia for a selected period of time. The goal of this study was to perform a contemporary epidemiological description of anaesthesia in France for the year 2010. METHODS: The data concerning private or public hospital stays were collected from the national PMSI database. All surgical/medical institutions performing anaesthesia in France and French Overseas Departments and Territories were queried concerning the number of anaesthesias, patient age, sex ratios, institution characteristics, hospitalization types, the duration of hospital stays, and the surgical procedures performed. RESULTS: In 2010, the number of anaesthesia procedures performed was 11,323,630 during 8,568,630 hospital stays. We found that 9,544,326 (84.3%) anaesthetic procedures were performed in adults (> 18 years of age; excluding childbirth), 845,568 (7.5%) were related to childbirth and 933,736 (8.2%) were acts in children (up to 18 years of age). The mean duration of hospital stay was 5.7+/-8.2 days. 56.5% of adults and 39.5% of children were managed as inpatient hospital stays. The male/female sex ratio and mean age were 42/58 and 54+/-19 years, respectively. In adults, anaesthesia was predominantly performed for abdominal surgery (24.5%), orthopaedics (16.7%), gynaecology (10.3%), ophthalmology (9.7%) and vascular surgeries (7.1%). For paediatric populations, the main surgical activities were Ear-Nose-Throat surgery (43.1%), orthopaedic surgery (15.1%) and urological surgeries (12.8%). DISCUSSION: The number of anaesthesias performed in France has dramatically increased (42.7%) since the last major epidemiological survey. Anaesthesia in the 21th century has been adapted to associated demographic changes: an older population with more comorbidities and fewer in-hospital procedures. PMID- 26141686 TI - Monitoring of oxygen saturation by near-infrared spectroscopy and paediatric cardiac surgery: Not just for the brain! PMID- 26141687 TI - Erratum: Evaluating a grading change at UCSD school of medicine: pass/fail grading is associated with decreased performance on preclinical exams but unchanged performance on USMLE step 1 scores. PMID- 26141688 TI - The hardest word: managers and leaders should say sorry too. PMID- 26141689 TI - Fomite-fingerpad transfer efficiency (pick-up and deposit) of Acinetobacter baumannii-with and without a latex glove. AB - BACKGROUND: Acinetobacter baumannii is a significant health care-associated pathogen because it is easily transmitted via fomites, extremely difficult to eradicate from the environment, and highly drug resistant. Understanding the environmentally mediated transmission dynamics of A baumannii is critical for more effective infection control. However, transfer efficiency of pathogen pick up and deposit remains poorly understood. Our study estimates the transfer efficiency of A baumannii with and without latex glove use from the fingerpad to a fomite and from a fomite to the fingerpad. METHODS: Fomite-fingerpad transfer efficiencies were determined for 6 materials (glass, stainless steel, porcelain, polypropylene, polycarbonate, and rubber). RESULTS: For A baumannii, the fomite to-fingerpad transfer efficiency was 24.1%, and the fingerpad-to-fomite transfer efficiency was 5.6%. When latex gloves were worn, the fomite-to-fingerpad transfer efficiency was reduced by 55.9% (to 10.6%) and the fingerpad-to-fomite transfer efficiency was reduced by 47.1% (to 3.0%). The average transfer efficiency between 2 skin surfaces was 32.5%. CONCLUSIONS: The fomite-to fingerpad transfer efficiency of A baumannii was statistically significantly higher than the fingerpad-to-fomite transfer efficiency, regardless of glove use. There was no significant difference in transfer efficiency by material type, except for rubber, which resulted in marginally higher transfer efficiencies. Our results underscore the importance of frequently changing gloves during patient care and frequent handwashing-hand hygiene during bare-handed care for the reduction of pathogen transmission. PMID- 26141692 TI - Outcomes of cold-stored venous allograft for below-knee bypasses in patients with critical limb ischemia. AB - OBJECTIVE: Critical limb ischemia (CLI), the most advanced form of peripheral arterial disease, is associated with strikingly high morbidity and mortality rates. Autogenous single-segment great saphenous vein (GSV) remains the optimal conduit for infrainguinal revascularization. Unfortunately, GSV is unavailable in up to 20% of patients. There is no consensus about the alternative graft that should be used for infragenicular bypass grafting when the GSV is unavailable. Currently, there are no outcome data for cold-stored venous allograft use in regard to recent safety and efficacy objective performance goals described by the Society for Vascular Surgery. METHODS: This is a retrospective analysis of 118 infragenicular revascularizations performed for CLI with cold-stored venous allografts obtained from varicose vein stripping surgery in a single institution from November 2002 to August 2013. RESULTS: Mean age (+/- standard deviation) was 75 +/- 12 years (male, 76%; diabetes, 73%; dialysis, 16%), and 38% (n = 45) had a history of failed ipsilateral revascularization. None had suitable autogenous conduit for even composite vein bypass. The distal anastomosis was performed to an infrapopliteal artery in 85 cases (72%). At 30 days, perioperative death rate was 6.8%, major adverse cardiovascular event rate was 7.6%, and major adverse limb event rate was 11.9%. Mean follow-up was 34 +/- 29 months (range, 1-113 months). At 1 year, freedom from major adverse limb event or perioperative death, limb salvage, survival, amputation-free survival, and secondary patency rates were, respectively, 64.9%, 82.5%, 85.4%, 73.3%, and 58.3%. Ejection fraction <45% and dialysis were the most significant factors predicting failure of revascularization. CONCLUSIONS: Cold-stored venous allografts may be used for performing infragenicular revascularization for CLI with acceptable safety and efficacy results despite poor long-term patency. Their level of performance remains inferior to autologous vein sources but seems comparable to alternative allografts or prosthetic conduit. Their availability is a major advantage compared with other biologic alternative sources. PMID- 26141693 TI - Examination of regional anesthesia for carotid endarterectomy. AB - OBJECTIVE: Carotid endarterectomy is the most effective treatment for reducing the risk of stroke in patients with significant carotid stenosis. Few studies have focused on the failure rate of regional anesthesia. METHODS: Data of all patients undergoing carotid endarterectomy (June 2009 to December 2014) in a single center were collected. Combined deep and superficial cervical plexus block or superficial plexus block alone was used according to the attending anesthesiologist's choice and the patient's characteristics (eg, dual antiplatelet or anticoagulation therapy). Intraoperative remifentanil (0.025-0.05 MUg/kg/min) was administered to maintain an adequate level of comfort, responsiveness, and cooperation. General anesthesia was planned only in the case of major contraindications or the patient's refusal of locoregional anesthesia. The primary end point of our study was the incidence of intraoperative conversion from locoregional to general anesthesia. RESULTS: A total of 2463 carotid endarterectomies were included in the analysis. Regional anesthesia was initially chosen in 2439 patients, whereas 24 patients received planned general anesthesia. In seven cases, regional anesthesia was converted to general anesthesia because of severe agitation of the patient (before clamping in four cases, after carotid clamping in two cases, and after declamping in one case). A shunt was used in 302 patients (12.3%) because of neurologic deterioration at the carotid clamping test. Intraoperative complications were emergent repeated surgical procedures in 13 cases (0.53%) because of acute neurologic deterioration, 1 intraoperative acute myocardial infarction (0.04%), and 3 cases (0.04%) of hemodynamically relevant supraventricular tachyarrhythmia. No intraoperative death occurred. In hospital mortality was 0.12% (three patients). Major stroke occurred in 23 patients (0.93%); minor stroke occurred in 16 patients (0.65%). The combined stroke and death rate was 1.62% (40 patients). CONCLUSIONS: In our practice, carotid endarterectomy under regional anesthesia is safe and associated with a very low rate of conversion to general anesthesia. PMID- 26141695 TI - Discussion. PMID- 26141694 TI - Obesity-related decrease in intraoperative blood flow is associated with maturation failure of radiocephalic arteriovenous fistula. AB - OBJECTIVE: Successful arteriovenous fistula (AVF) maturation is often challenging in obese patients. Optimal initial intraoperative blood flow (IOBF) is essential for adequate AVF maturation. This study was conducted to elucidate the effect of obesity on IOBF and radiocephalic AVF maturation. METHODS: Patients with a newly created radiocephalic AVF were included (N = 252). Obesity was defined as a baseline body mass index (BMI) >=25 kg/m(2), and primary maturation failure was defined as failure to use the AVF successfully by 3 months after its creation. IOBF was measured immediately after construction of the AVF with a VeriQ system (MediStim, Oslo, Norway). RESULTS: The mean BMI was 24.1 +/- 3.9 kg/m(2), and the prevalence of obesity was 31.3%. Particularly, 8.3% (21 patients) had a BMI >=30 kg/m(2). Primary maturation failure occurred in 100 patients (39.7%), and an IOBF <190 mL/min was closely associated with the risk of maturation failure (relative risk, 3.05; 95% confidence interval, 1.52-6.11). Compared with nonobese patients, obese subjects had a significantly higher prevalence of diabetes and elevated high-sensitivity C-reactive protein levels, whereas diameters of vessels were similar. When the patients were further divided into three groups as BMI <25, 25 to 29.9, and >=30 kg/m(2), patients in the higher BMI group showed significantly lower IOBF and higher maturation failure rate. According to multivariate analysis, the statistically significant variables that determined maturation failure were obesity, previous vascular disease, increased high-sensitivity C reactive protein levels, and IOBF <190 mL/min. CONCLUSIONS: Obese patients had a significantly lower IOBF, and both obesity and low IOBF contributed to the primary maturation failure of AVF. Obesity-associated inflammation and atherosclerosis might play roles in this association. PMID- 26141696 TI - Cuban Americans have the highest rates of peripheral arterial disease in diverse Hispanic/Latino communities. AB - OBJECTIVE: Because Hispanic ethnicity in the United States is heterogeneous, the purpose of this study was to determine the epidemiology of peripheral arterial disease (PAD) within U.S. Hispanic/Latino groups defined by national background. METHODS: This analysis included 9648 men and women older than 45 years enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The ankle brachial index (ABI) was computed as the higher of the posterior tibial and dorsalis pedis systolic blood pressures for each leg divided by the higher brachial artery systolic blood pressure. The index ABI was the higher of the two. An ABI <=0.90 was the criterion for the presence of PAD. RESULTS: The mean age was 56 years, and 55% were female. Overall, the prevalence of an ABI <=0.90 (PAD), 0.90 to 0.99 (borderline), 1.0 to 1.39 (normal), and >=1.40 (high) was 5.7%, 19.3%, 72.5%, and 2.6%, respectively. After multivariable adjustment for PAD risk factors and compared with Mexicans, Cubans had a nearly threefold higher odds for PAD (odds ratio, 2.9; 95% confidence interval, 1.9-4.4). The odds of PAD for the other Hispanic/Latino groups ranged from 1.2 to 1.8. Although men had a more than threefold higher odds of an ABI >=1.40 (3.6; 2.0-6.5), the odds did not differ significantly by Hispanic/Latino background. CONCLUSIONS: Compared with Mexican Americans, all other Hispanic/Latino background groups have a significantly higher odds of having PAD, with the odds being nearly threefold higher among Cubans. PMID- 26141697 TI - The influence of cephalic vein diameter and diabetes on primary maturation and patency of autogenous radiocephalic arteriovenous fistulas. AB - OBJECTIVE: This study identified predictors affecting maturation and patency of autogenous radiocephalic arteriovenous fistulas (RCAVFs). METHODS: We retrospectively reviewed the prospectively collected clinical data of all patients who underwent primary RCAVF creation and evaluated the effect of clinical variables and findings of preoperative duplex ultrasound mapping on primary maturation and patency rates of RCAVFs. RESULTS: From August 2008 to December 2010, 383 vascular access procedures were performed in 371 patients; of these, 331 (86.4%) were autogenous AVFs, 283 (85.5%) were primary first AVFs, and 186 (65.7%) of these were RCAVFs. The primary maturation rate was 88.2% at a mean of 39 +/- 24.1 days after the operation. By multiple logistic regression analysis, minimum cephalic vein (CV) diameter >2 mm was an independent predictor of RCAVF maturation (odds ratio, 3.672; 95% confidence interval, 1.394-9.673; P = .008), which was more easily achieved in nondiabetic patients. During the mean follow-up of 47.2 +/- 23.1 months, primary patency of RCAVFs was 80.3% at 1 year and 76.5% at 2 years. A Cox proportional hazard model showed diabetes was the only independent risk factor of primary patency (hazard ratio, 2.008; 95% confidence interval, 1.022-3.945; P = .043). Nondiabetic patients with a CV diameter >2 mm had significantly higher primary maturation rate and higher primary patency than diabetic patients with a CV diameter <=2 mm. CONCLUSIONS: There were different risk factors affecting RCAVF primary maturation and primary patency. A CV with a small-diameter of <=2 mm combined with diabetes was an independent risk factor of failure not only of primary maturation but also of primary patency in RCAVF. PMID- 26141698 TI - Exploring patient involvement in decision making for vascular procedures. AB - BACKGROUND: Developing patient-centered approaches to health care requires increased engagement of patients in their own care, including treatment decisions. Current levels of patient involvement in treatment choices have not been quantified, however, and whether patients desire greater decision-making responsibility is unknown. We conducted a prospective study to explore patients' desired vs experienced roles in treatment decisions, characterize perceptions of treatment outcomes, and identify important sources of information. METHODS: Patients undergoing elective vascular procedures completed a survey consisting of multiple choice, Likert scale, and open-ended questions. Statistics are displayed as mean +/- standard deviation or count (%). Differences among procedure categories were evaluated using chi(2) or the Fisher exact test at P < .05 based on responses scored 1 to 2, indicating importance, agreement, or satisfaction based on a 1 to 5 Likert scale where 1 = "very important," "strongly agree" or "very satisfied". RESULTS: Of 101 patients who were contacted, 81 participated. Procedure categories included abdominal aortic aneurysm (AAA) repair in 20, arteriovenous (AV) hemodialysis access in 21, carotid endarterectomy (CEA) in 20, and intervention for lower extremity peripheral arterial disease (PAD) in 20. Participants preferred discussion of all treatments being considered vs only the provider's recommended treatment (90% vs 56%) and choosing together with the provider vs having the provider choose for them (93% vs 62%). Although participants indicated adequate information to ask questions without feeling overwhelmed, only 77% agreed that they had the opportunity to ask questions and only 54% indicated that they were offered a choice. Thirty-seven participants (46%) considered their first treatment was successful, 38% considered a subsequent treatment was successful, and 16% considered none of their treatments were successful. Participants undergoing PAD and AV access procedures most often felt confused or overwhelmed (25% and 24%, respectively, vs 0% for AAA and CEA; P < .01). Patients with PAD had adequate information least often (70% vs 85% for AAA, 100% for AV access, and 95% for CEA; P = .01), had the lowest satisfaction with understanding of their diagnosis (65% vs 95% for AAA, 100% for AV access, and 95% for CEA; P < .01), and most often considered none of their treatments successful (35% vs 0% for AAA, 15% for AV access, and 15% for CEA; P = .02). Providers were identified as the most important information source. CONCLUSIONS: Patients have variable levels of participation in decision making related to vascular procedures and often consider their treatments unsuccessful. Although providers are important sources of information, patients still prefer to discuss all options being considered and contribute to shared decision making. PMID- 26141699 TI - Management of late main-body aortic endograft component uncoupling and type IIIa endoleak encountered with the Endologix Powerlink and AFX platforms. AB - OBJECTIVE: Junctional component separation producing type IIIa endoleak after endovascular abdominal aortic aneurysm repair (EVAR) is an uncommon but serious complication requiring unanticipated reinterventions. This retrospective study analyzed main-body EVAR component uncoupling and type IIIa endoleaks encountered with Powerlink and AFX (Endologix Inc, Irvine, Calif) endografts during an 8-year period. METHODS: Type IIIa endoleaks were identified from a database of secondary interventions and clinical surveillance. Operative reports, medical records, and computed tomography studies were reviewed. Clinical and imaging characteristics were analyzed over time, and differences were compared at appropriate follow-up intervals. RESULTS: Since 2006, 701 patients underwent primary EVAR using Endologix Powerlink (352 patients, 2006-2011) or AFX (349 patients, 2011-2014) endografts. Endoleaks required 32 secondary interventions (4.6%), including type Ia in 4 patients (1 proximal extension and 3 explants); type Ib in 8 patients (all distal extensions for enlarging iliac aneurysms); type II in 1 patient (explant); type IIIa in 17 patients (2.4%), who were the subject of this report; and type IIIb in 2 patients (both EVAR relining). The 17 patients with type IIIa endoleak were an average age of 71 years, and 14 (82%) were men. The mean preoperative abdominal aortic aneurysm (AAA) diameter was 70 +/- 18 mm. The repair was elective in 16 patients and an emergency in one. Ten cases were performed with Powerlink and seven with AFX. Analysis of serial computed tomography scans found significant changes in AAA diameter; renal-to-bifurcation straight-line, centerline, and greater curvature lengths; EVAR angulation; and loss of EVAR component overlap. The average time from EVAR to reintervention was 32 months. Three patients returned with a ruptured AAA and three with AAA thrombosis, and three of these patients (18%) died <=30 days of the emergency reintervention. Secondary procedures included EVAR relining with additional bridging components in 14 patients (82%), explant in 2, and axillobifemoral bypass in 1. No new cases of endograft uncoupling have been identified in patients treated with AFX since December 2012 after adoption of revised instructions for use. CONCLUSIONS: Although a small number of secondary interventions were needed after EVAR with the Endologix Powerlink or AFX endografts, most were undertaken for late main-body component uncoupling and type IIIa endoleak, which can occur after sideways displacement of the endograft in large and angulated AAAs. Patients treated before 2013 under the old instructions for use should be evaluated for signs of impending component separation and monitored annually, noting that expected indicators of endograft failure, such as increasing AAA diameter and endoleak, may be absent. PMID- 26141700 TI - Alternative transcripts of the SERPINA1 gene in alpha-1 antitrypsin deficiency. AB - BACKGROUND: SERPINA1 is the gene for alpha-1 antitrypsin (AAT), an acute phase protein with anti-protease and immunoregulatory activities. Mutations in SERPINA1 gene cause AAT deficiency and predispose individuals to early-onset emphysema and liver diseases. Expression of the SERPINA1 gene is regulated by different promoters and alternative splicing events among non-coding exons 1A, 1B and 1C. METHODS: We have developed three quantitative PCR (QT-PCR) assays (1A, 1B and 1C). These assays were applied for the analysis of SERPINA1 alternative transcripts in: (1) 16 human tissues and (2) peripheral blood leukocytes from 33 subjects with AAT mutations and 7 controls. RESULTS: Tissue-specific expression was found for the SERPINA1 transcripts. The 1A transcripts were mainly expressed in leukocytes and lung tissue while those detected with the 1B assay were highly restricted to leukocytes. Only 1B transcripts significantly correlated with serum AAT levels. The 1C transcripts were specifically found in lung, liver, kidney and pancreas. Furthermore, the expression of transcripts was related to AAT genotypes. While deficient variants of AAT had no pronounced effect on the transcript expression, null alleles were associated with significant reduction of different transcripts. CONCLUSIONS: The possibility to discriminate between SERPINA1 alternative splicing products will help us to understand better the regulation of SERPINA1 gene and its association with SERPINA1 mutations-related diseases. PMID- 26141701 TI - Microarray profiling of long non-coding RNA (lncRNA) associated with hypertrophic cardiomyopathy. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an inherited disorder with around 1400 known mutations; however the molecular pathways leading from genotype to phenotype are not fully understood. LncRNAs, which account for approximately 98 % of human genome, are becoming increasingly interesting with regard to various diseases. However, changes in the expression of regulatory lncRNAs in HCM have not yet been reported. To identify myocardial lncRNAs involved in HCM and characterize their roles in HCM pathogenesis. METHODS: Myocardial tissues were obtained from 7 HCM patients and 5 healthy individuals, and lncRNA and mRNA expression profiles were analyzed using the Arraystar human lncRNA microarray. Real-time PCR was conducted to validate the expression pattern of lncRNA and mRNA. Gene ontology (GO) enrichment and KEGG analysis of mRNAs was conducted to identify the related biological modules and pathologic pathways. RESULTS: Approximately 1426 lncRNAs (965 up-regulated and 461 down-regulated) and 1715 mRNAs (896 up-regulated and 819 down-regulated) were aberrantly expressed in HCM patients with fold change > 2.0. GO analysis indicated that these lncRNAs coexpressed mRNAs were targeted to translational process. Pathway analysis indicated that lncRNAs-coexpressed mRNAs were mostly enriched in ribosome and oxidative phosphorylation. CONCLUSION: LncRNAs are involved in the pathogenesis of HCM through the modulation of multiple pathogenetic pathways. PMID- 26141702 TI - Post-zygotic selection against parental genotypes during larval development maintains all-hybrid populations of the frog Pelophylax esculentus. AB - BACKGROUND: Hybridization between two species usually leads to inviable or infertile offspring, due to endogenous or exogenous selection pressures. Yet, hybrid taxa are found in several plant and animal genera, and some of these hybrid taxa are ecologically and evolutionarily very successful. One example of such a successful hybrid is the water frog, Pelophylax esculentus which originated from matings between the two species P. ridibundus (genotype RR) and P. lessonae (LL). At the northern border of the distribution all-hybrid populations consisting of diploid (LR) and one or two triploid (LLR, LRR) frog types have been established. Here, the hybrid has achieved reproductive independence from its sexual ancestors and forms a self-sustaining evolutionary unit. Based on the gamete production of these hybrids, certain mating combinations should lead to LL and RR offspring, but these parental forms are absent among the adults. RESULTS: In order to investigate the mechanisms that maintain such an all-hybrid system, we performed a field study and a crossing experiment. In the field we sampled several ponds for water frog larvae at different developmental stages. Genotype compositions were then analysed and life history differences between the genotypes examined. In the experiment we crossed diploid and triploid males and females from different ponds and determined fertilization success as well as development speed and survival rates of the offspring under high, medium and low food availability. In both parts of the study, we found numerous LL and RR offspring during the egg and early larval stages; but the frequency of these parental genotypes decreased drastically during later stages. In natural ponds almost all of them had disappeared already before metamorphosis; under the more benign experimental conditions the last ones died as juveniles during the following year. CONCLUSIONS: From the combined results we conclude that the absence of parental genotypes in all-hybrid populations is due to post-zygotic selection against them, rather than to pre zygotic mechanisms that might prevent their formation in the first place. For this post-zygotic selection, genetic mechanisms resulting from low genetic diversity and fixation of deleterious mutations seem to be a more likely explanation than ecological factors. PMID- 26141703 TI - Targeting lipid peroxidation and mitochondrial imbalance in Friedreich's ataxia. AB - Friedreich's ataxia (FRDA) is an autosomal recessive disorder, caused by reduced levels of the protein frataxin. This protein is located in the mitochondria, where it functions in the biogenesis of iron-sulphur clusters (ISCs), which are important for the function of the mitochondrial respiratory chain complexes. Moreover, disruption in iron biogenesis may lead to oxidative stress. Oxidative stress can be the cause and/or the consequence of mitochondrial energy imbalance, leading to cell death. Fibroblasts from two FRDA mouse models, YG8R and KIKO, were used to analyse two different categories of protective compounds: deuterised poly-unsaturated fatty acids (dPUFAs) and Nrf2-inducers. The former have been shown to protect the cell from damage induced by lipid peroxidation and the latter trigger the well-known Nrf2 antioxidant pathway. Our results show that the sensitivity to oxidative stress of YG8R and KIKO mouse fibroblasts, resulting in cell death and lipid peroxidation, can be prevented by d4-PUFA and Nrf2-inducers (SFN and TBE-31). The mitochondrial membrane potential (DeltaPsim) of YG8R and KIKO fibroblasts revealed a difference in their mitochondrial pathophysiology, which may be due to the different genetic basis of the two models. This suggests that variable levels of reduced frataxin may act differently on mitochondrial pathophysiology and that these two cell models could be useful in recapitulating the observed differences in the FRDA phenotype. This may reflect a different modulatory effect towards cell death that will need to be investigated further. PMID- 26141704 TI - Emerging molecules in the interface between skeletal system and innate immunity. AB - Despite the improved treatment of bone destruction, significant unmet medical need remains. For example, there is a limited benefit of continued bisphosphonate therapy for osteoporotic patients, and only minor populations of rheumatoid arthritis patients obtain biologic-free remission. Therefore, the identification of a novel therapeutic target for bone destructive diseases remains an important issue in the field of skeletal biology. To date there has been little progress in identifying osteo-innate-immunological regulators that could be used for the prophylactic treatment of inflammatory bone destruction. Recently, we identified several new molecules that are critical osteo-innate-immunological regulators by using gene targeting technology. These findings may offer an invaluable opportunity to regulate bone-destructive diseases, such as osteoporosis and rheumatoid arthritis. PMID- 26141705 TI - Immune therapy of non-small cell lung cancer. The future. AB - Surgery is still the best treatment option of lung cancer but only one third of patients are operable and prognosis remains mediocre in operated patients, with the exception of initial stages. Medical treatment is fast moving toward new frontiers. New insights in the biology of cancer development led to discovery of new drugs, which are more effective as compared to conventional platinum based chemotherapy. A new approach to immunotherapy based on immune-check point represents a remarkable innovation in lung cancer treatment. Initial trials with anti PD-1 antibodies in metastatic patients provided results never observed with previously known drug categories. Several key question need to be answered to identify patients most likely to respond to anti PD-1/anti PD-L1 treatments, to assess the role of combined treatment modalities including immune check point receptor block (associations with surgery, chemotherapy, ITKs), and to boost host immune response, possibly by lowering his systemic inflammation and improving nutritional status. PMID- 26141706 TI - Predictive validity of a five-item symptom checklist to screen psychiatric morbidity and suicide ideation in general population and psychiatric settings. AB - BACKGROUND/PURPOSE: Suicide is a major concern in public health worldwide. Early identification of individuals at risk is critical for suicide prevention. The present study revised the 5-item Brief Symptom Rating Scale (BSRS-5) to a checklist format (BSRS-5R) and validated the BSRS-5R into a screening tool for psychiatric morbidity and suicide ideation in the general public. METHODS: The study participants consisted of two subsets of sample from community residents and psychiatric patients. The community subjects were recruited from stratified proportional randomization sampling in a nationwide community survey, while the psychiatric patients were from psychiatric outpatient service and psychiatric daycare unit in a teaching hospital in northern Taiwan. All participants responded to the questionnaire investigating the BSRS-5, personal experience with suicide, and demographic information. RESULTS: In total, 2147 community respondents and 700 respondents from psychiatric settings completed the survey questions. The BSRS-5R was highly correlated to BSRS-5 with good internal consistency in our study sample. For the community subjects, receiver operating characteristic curve analysis revealed an optimal cutoff of 2/3 for BSRS-5R to discriminate psychiatric morbidity or suicide ideation. The BSRS-5R could also identify psychiatric morbidity in psychiatric outpatients and daycare patients. In addition, the cutoff of 4/5 for BSRS-5R to determine suicide ideation yielded moderately good predictive validity in psychiatric outpatients and in daycare patients. CONCLUSION: The BSRS-5R was validated as an efficient checklist to screen for psychiatric morbidity and suicide ideation in the general public. The result is valuable in translating into general medical and community settings for early detection of suicide ideation. PMID- 26141707 TI - Mental Health Services in School-Based Health Centers: Systematic Review. AB - Mental health issues affect 20-25% of children and adolescents, of which few receive services. School-based health centers (SBHCs) provide access to mental health services to children and adolescents within their schools. A systematic review of literature was undertaken to review evidence on the effectiveness of delivery of mental health services in SBHCs. Databases were searched extensively for research studies published between January 1990 and March 2014. Data analysis was based on the method proposed by the Centre for Reviews and Dissemination. Twenty-three studies were selected for review. Each study was explored for accessibility and content of mental health services in SBHCs. SBHCs provide access and eliminate barriers to mental health services. Students who exhibited high-risk behaviors were more likely to have sought services at the SBHC. However, there is a lack of high-quality research evaluating mental health services in the SBHCs and their effect on children and adolescents. PMID- 26141708 TI - Reply: Pesticide residues and semen quality. PMID- 26141709 TI - Pesticide residues and semen quality. PMID- 26141710 TI - Reducing low-value care in endometriosis between limited evidence and unresolved issues: a proposal. AB - Quantification of benefits and harms of medical interventions should be based on high-quality evidence, which is not always the case in the endometriosis field. In many clinical circumstances, healthcare decisions in women with endometriosis are taken based on suboptimal evidence or on evidence of coexistence of benefits and harms that must be balanced. In these conditions, it is important to avoid or reduce the use of low-value care, i.e. interventions with defined harms and uncertain benefits, or whose effectiveness is comparable with less expensive alternatives. In particular, we suggest that: (i) non-surgical diagnosis based on symptoms, physical findings and transvaginal ultrasonography is possible in most women with symptomatic endometriosis. Thus, except in doubtful cases, laparoscopy should be intended for surgical treatment, not for diagnostic purposes: early diagnosis and diagnostic laparoscopy are not synonymous; (ii) future trials on new drugs for endometriosis should address those outcomes that are most important to patients, should be designed as superiority trials and should include a progestin or an estrogen-progestin as a comparator. Moreover, limitation of repetitive surgery for recurrent endometriosis is among the objectives of long term medical treatment; (iii) indications for surgery should be the result of a balance between demonstrated benefits in terms of fertility enhancement and pain relief, specific risks associated with excision of different types of endometriotic lesions, cost-effectiveness and patient preference after detailed information; (iv) physicians, health professionals and policy makers should discriminate between screening for and diagnosis of endometriosis. Limited peritoneal foci, which are frequently observed also in asymptomatic women, regress or remain stable in about two thirds of cases. Therefore, the theoretical premises for a screening campaign are currently unclear; (v) physicians should develop the ability to effectively communicate quantitative information based on international guidelines and systematic literature reviews. This will assist a woman's understanding of the interaction between the evidence and her priorities, facilitating the transition towards value-based medicine. PMID- 26141711 TI - Linear reduction in thyroid cancer risk by oral contraceptive use: a dose response meta-analysis of prospective cohort studies. AB - STUDY QUESTION: Is there an association between oral contraceptive (OC) use and thyroid cancer risk in females? SUMMARY ANSWER: OC use is inversely associated with the risk of thyroid cancer in females. WHAT IS KNOWN ALREADY: OC use may be relevant to the risk of thyroid cancer as suggested by some epidemiological studies. However, the findings are inconsistent regarding the effect direction and size. STUDY DESIGN, SIZE, DURATION: This systematic review and meta-analysis included a total of 1906 patients from about 1.3 million individuals who had participated in 9 prospective cohort studies. The follow-up length ranged 7.5 15.9 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: PubMed (MEDLINE) was searched through to January 2015 for eligible studies. References of relevant review articles were also manually screened. Prospective cohort studies that evaluated the association between OC use and thyroid cancer risk were included. Study characteristics including patients' characteristics, length of the follow up and risk estimates were extracted. The quality of the studies was also assessed. MAIN RESULTS AND THE ROLE OF CHANCE: The included studies were of high methodological quality according to the Newcastle-Ottawa Quality Assessment Scale. After pooling risk estimates from all the studies, there was a significant inverse association between the longest versus shortest duration of OC use and the risk of thyroid cancer [relative risk (RR) = 0.84, 95% confidence interval (CI) 0.73-0.97], with no considerable heterogeneity (I(2) = 26.1%). There was no significant publication bias. The significant association persisted in the subgroup of high-quality studies (RR = 0.84, 95% CI 0.72-0.97). By dose-response analysis, there was a linear relationship (P = 0.0001) between the duration of OC use and thyroid cancer risk. The summary RR for an increment of 1 year of OC use was 0.96 (95% CI 0.94-0.98), with no significant heterogeneity. LIMITATIONS, REASONS FOR CAUTION: Individual patient data were unavailable for a more accurate estimation. WIDER IMPLICATIONS OF THE FINDINGS: These results indicate that OC use may decrease the risk of thyroid cancer in females. This may have implications for women's decisions regarding the use of OC. STUDY FUNDING/COMPETING INTERESTS: No funding was involved for this study. No conflicts of interest are declared. PMID- 26141712 TI - Economic aspects of infertility care: a challenge for researchers and clinicians. AB - Infertility care has improved remarkably over the last few decades and has received growing attention from health care providers. Several treatments, including expensive options such as Assisted Reproductive Techniques, are now widely available for routine clinical use. In most cases, adoption of these treatments has occurred without robust cost-effective analyses. IVF for unexplained infertility and ICSI in the absence of semen abnormalities are two examples of this gradual technology creep. More in-depth economic analyses in the field of infertility are undoubtedly warranted. However, performing these analyses is challenging because infertility care poses a number of unique challenges. Studies of cost-effectiveness are open to criticism because there is a lack of consensus about the outcomes of choice and the appropriate perspective. The use of quality adjusted life years (QALYs) to allow comparisons with other clinical conditions is also controversial because the value associated with infertility care cannot be easily captured in QALYs. Moreover, their use triggers the crucial question of whose QALYs merit consideration-an individual's, a couple's or a child's. In conclusion, economic analysis in infertility represents a peculiar but crucial challenge. If management of infertility is to become an integral part of publicly or privately funded health care systems worldwide, better quality data and a shared vision about the costs and benefits of infertility treatments are needed. PMID- 26141713 TI - Fertility preservation in the male pediatric population: factors influencing the decision of parents and children. AB - STUDY QUESTION: How can the decision process for fertility preservation (FP) in adolescents and prepubertal boys be improved based on patient and parent feelings about FP counseling? SUMMARY ANSWER: The content of information given to patients and parents and hope for future parenthood appeared to positively impact on the decision to preserve fertility in the pediatric population and, therefore, deserves special attention to improve FP care. WHAT IS KNOWN ALREADY: A vast body of literature on adult cancer patients shows that reproductive capacity is a major quality-of-life issue. Patients also have a strong desire to be informed of available FP options with a view to future parenthood of their own genetic child, considering that <10% chose to adopt or used donated gametes. Furthermore, the quality of fertility counseling provided at the time of cancer diagnosis has been identified as a crucial factor in the decision-making process. By contrast, in the pediatric population, while it was shown that parents were able to make an informed and voluntary decision for their prepubertal sons despite the heavy emotional burden at the time of diagnosis, there is so far very limited information on patient expectations regarding FP. A lack of awareness often equates to suboptimal care by oncologists and FP specialists, and poor access to FP, therefore improving knowledge and identifying the expectations of pediatric patients and their parents are crucial for optimizing multidisciplinary collaborative care pathways (MCCPs), including counseling and access to FP methods, in the youngest population. STUDY DESIGN, SIZE, DURATION: A questionnaire survey was posted to an eligible population between May 2005 and May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 348 prepubertal boys and adolescents aged 0-18 years, diagnosed with cancer in a university hospital setting, were eligible. Three different questionnaires for two age groups of children (<12 and 12-18 years) and parents were established based on information from focus groups. Questions were subsequently reviewed by the institutional ethics board before being sent. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 348 eligible patients, 44 died and 14 were lost to follow-up. Thus, 290 patients (77 aged 12-18 years and 213 aged <12 years) were sent a questionnaire. In total, 120 questionnaires were recovered, 45.5% (n = 35/77) from adolescents and 39.9% (n = 85/213) from children. FP acceptance rates were, respectively, 74 and 78.6% for boys aged <12 and 12-18 years. The content of information provided to patients and parents appeared to positively impact on the decision to preserve fertility (P = 0.04). While the majority of boys aged >12 years considered the information to be clear (72%), complete (80%) and understandable (90.9%), only 33.3% of boys aged <12 years were able to comprehend the information. Pressure from doctors to reduce the delay between diagnosis and cancer treatment increased the number of refusals (P<0.01), while hope for future parenthood favored acceptance (P < 0.01). Family support was considered important for 75% of adolescents and 58% of children, and medical support for 50% of adolescents and 42% of children. LIMITATIONS, REASON FOR CAUTION: This single center survey does not allow extrapolation of the information to other settings. Recall bias and lack of full external validation of the questionnaires are further limitations. Modification of the current MCCP should be further evaluated according to our results. WIDER IMPLICATIONS OF THE FINDINGS: Acknowledging the issues faced and familiarizing oneself with the care of patients undergoing fertility-threatening therapies supply primary care providers with the appropriate quality management tools in the field of FP in centers for reproductive medicine. Expectations reported in the survey allow appropriate support to be included within the MCCP design. STUDY FUNDING/COMPETING INTERESTS: Funding by hospital/clinic(s); Cliniques Universitaires Saint Luc, Brussels, Belgium. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: NCT02411214. PMID- 26141714 TI - Congenital combined pituitary hormone deficiency patients have better responses to gonadotrophin-induced spermatogenesis than idiopathic hypogonadotropic hypogonadism patients. AB - STUDY QUESTION: Do patients with congenital combined pituitary hormone deficiency (CCPHD) have different responses to gonadotrophin-induced spermatogenesis compared with those with idiopathic hypogonadotropic hypogonadism (IHH)? SUMMARY ANSWER: CCPHD patients have a better response to gonadotrophin therapy than IHH patients. WHAT IS KNOWN ALREADY: Gonadotrophins are effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism. DESIGN, SIZE AND DURATION: This retrospective cohort study included 75 patients, 53 of whom had IHH and 22 CCPHD. They were diagnosed, treated and followed up between January 2008 and December 2013. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Combined gonadotrophin therapy, consisting of human chorionic gonadotrophin and human menopausal gonadotrophin, was administered for 24 months. The success rate of spermatogenesis (>=1 sperm in ejaculate), serum total testosterone level, testicle size and sperm concentration during the treatment, as well as the first time sperm were detected in the ejaculate, were compared between the two diagnostic groups. All patients were treated in Peking Union Medical College Hospital. MAIN RESULTS AND THE ROLE OF CHANCE: Spermatogenesis was successfully induced in 85% of IHH patients and 100% of CCPHD patients after 24-month combined gonadotrophin treatment (P = 0.03). In comparison with IHH, CCPHD patients had larger mean testicle sizes during the gonadotrophin treatment at 6, 12, 18 and 24 months (all P < 0.05). The initial time for sperm appearance in IHH group (n = 45) and CCPHD group (n = 22) was 13.2 +/- 5.9 versus 10.4 +/- 3.8 months (P = 0.045). Generally, CCPHD patients had higher sperm counts [median (quartiles)] than IHH patients during the treatment, but the difference was only statistically significant at 12 months of treatment, 3.3 (1.8, 12.0) versus 1.0 (0.0, 4.6) million/ml, P = 0.001. There was a higher level of serum total testosterone [mean (SD)] in the CCPHD group than the IHH group (676 +/- 245 versus 555 +/- 209 ng/dl, P = 0.035). LIMITATIONS, REASONS FOR CAUTION: First, the inherent nature of a retrospective designed study was a main shortcoming. Secondly, pathological gene mutations in IHH and CCPHD patients should be further investigated. Clarification of the underlying mechanisms between cryptorchidism and mutated genes may provide more information for the divergent therapeutic responses between two groups. Only a minority of patients were actively seeking to have children so information about fertility is limited. WIDER IMPLICATIONS OF THE FINDINGS: CCPHD patients had a lower incidence of cryptorchidism and a better response to gonadotrophin therapy than IHH patients, reflecting multiple defects on the different levels of reproduction axis in IHH. Furthermore, growth hormone is not indispensable for spermatogenesis in CCPHD patients. STUDY FUNDING/COMPETING INTERESTS: The study was supported by Natural Science Foundation of China (No: 81100416). None of the authors has any conflicts of interest to declare. PMID- 26141715 TI - The roles of cross-talk epigenetic patterns in Arabidopsis thaliana. AB - The epigenetic mechanisms, including histone modifications, DNA cytosine methylation, histone variants and noncoding RNAs (ncRNAs), play a key role in determining transcriptional outcomes. Recently, many studies have demonstrated that the different epigenetic mechanisms interplay with each other rather than work independently. In this article, we outline a framework for how different epigenetic mechanisms work with each other in Arabidopsis thalianaWe build a network of cross-talk between chromatin marks based on six classes of cross-talk interactions. The first pattern details coordinated modifications that act together to enhance or repress gene expression. The second pattern details bivalent modifications that act antagonistically toward gene expression. The third pattern is for unilateral promotion of one modification by the existence of another modification. The fourth pattern is for unilateral inhibition of one modification by another modification. The fifth pattern is for mutual inhibitory patterns. The sixth pattern is for epigenetic modifications that appear independent.We also explore the mutual regulation between chromatin marks and ncRNAs in various ways. These regulations can be divided into six parts: how ncRNA affects the binding of chromatin mark, such as miR2Epi, siR2Epi and lncR2Epi; how chromatin mark regulates ncRNA, such as Epi2miR, Epi2siR and Epi2lncR.A comprehensive network of cross-talk between different epigenetic mechanisms will help in fully understanding the functional roles and biological impacts of epigenetic regulation. PMID- 26141717 TI - Sedation methods for intra-articular corticosteroid injections in Juvenile Idiopathic Arthritis: a review. AB - Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Intra-articular corticosteroid injection (IASI), one of the cornerstones of treatment for this disease, is usually associated with anxiety and pain. IASI in JIA may be performed under general anesthesia, conscious sedation, or local anesthesia alone. Currently, there is no widely accepted standard of care regarding the sedation method for IASI. This review discusses the different methods of anesthesia and sedation in this procedure, emphasizing the advantages and shortcomings of each method. PMID- 26141716 TI - Deprescribing benzodiazepines and Z-drugs in community-dwelling adults: a scoping review. AB - BACKGROUND: Long-term sedative use is prevalent and associated with significant morbidity, including adverse events such as falls, cognitive impairment, and sedation. The development of dependence can pose significant challenges when discontinuation is attempted as withdrawal symptoms often develop. We conducted a scoping review to map and characterize the literature and determine opportunities for future research regarding deprescribing strategies for long-term benzodiazepine and Z-drug (zopiclone, zolpidem, and zaleplon) use in community dwelling adults. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, CINAHL, TRIP, and JBI Ovid databases and conducted a grey literature search. Articles discussing methods for deprescribing benzodiazepines or Z-drugs in community-dwelling adults were selected. RESULTS: Following removal of duplicates, 2797 articles were reviewed for eligibility. Of these, 367 were retrieved for full-text assessment and 139 were subsequently included for review. Seventy-four (53%) articles were original research, predominantly randomized controlled trials (n = 52 [37%]), whereas 58 (42%) were narrative reviews and seven (5%) were guidelines. Amongst original studies, pharmacologic strategies were the most commonly studied intervention (n = 42 [57%]). Additional deprescribing strategies included psychological therapies (n = 10 [14%]), mixed interventions (n = 12 [16%]), and others (n = 10 [14%]). Behaviour change interventions were commonly combined and included enablement (n = 56 [76%]), education (n = 36 [47%]), and training (n = 29 [39%]). Gradual dose reduction was frequently a component of studies, reviews, and guidelines, but methods varied widely. CONCLUSIONS: Approaches proposed for deprescribing benzodiazepines and Z-drugs are numerous and heterogeneous. Current research in this area using methods such as randomized trials and meta-analyses may too narrowly encompass potential strategies available to target this phenomenon. Realist synthesis methods would be well suited to understand the mechanisms by which deprescribing interventions work and why they fail. PMID- 26141718 TI - A genome-scale mining strategy for recovering novel rapidly-evolving nuclear single-copy genes for addressing shallow-scale phylogenetics in Hydrangea. AB - BACKGROUND: Identifying orthologous molecular markers that potentially resolve relationships at and below species level has been a major challenge in molecular phylogenetics over the past decade. Non-coding regions of nuclear low- or single copy markers are a vast and promising source of data providing information for shallow-scale phylogenetics. Taking advantage of public transcriptome data from the One Thousand Plant Project (1KP), we developed a genome-scale mining strategy for recovering potentially orthologous single-copy markers to address low-scale phylogenetics. Our marker design targeted the amplification of intron-rich nuclear single-copy regions from genomic DNA. As a case study we used Hydrangea section Cornidia, one of the most recently diverged lineages within Hydrangeaceae (Cornales), for comparing the performance of three of these nuclear markers to other "fast" evolving plastid markers. RESULTS: Our data mining and filtering process retrieved 73 putative nuclear single-copy genes which are potentially useful for resolving phylogenetic relationships at a range of divergence depths within Cornales. The three assessed nuclear markers showed considerably more phylogenetic signal for shallow evolutionary depths than conventional plastid markers. Phylogenetic signal in plastid markers increased less markedly towards deeper evolutionary divergences. Potential phylogenetic noise introduced by nuclear markers was lower than their respective phylogenetic signal across all evolutionary depths. In contrast, plastid markers showed higher probabilities for introducing phylogenetic noise than signal at the deepest evolutionary divergences within the tribe Hydrangeeae (Hydrangeaceae). CONCLUSIONS: While nuclear single-copy markers are highly informative for shallow evolutionary depths without introducing phylogenetic noise, plastid markers might be more appropriate for resolving deeper-level divergences such as the backbone relationships of the Hydrangeaceae family and deeper, at which non-coding parts of nuclear markers could potentially introduce noise due to elevated rates of evolution. The herein developed and demonstrated transcriptome based mining strategy has a great potential for the design of novel and highly informative nuclear markers for a range of plant groups and evolutionary scales. PMID- 26141719 TI - MiR-190b, the highest up-regulated miRNA in ERalpha-positive compared to ERalpha negative breast tumors, a new biomarker in breast cancers? AB - BACKGROUND: MicroRNAs (miRNAs) show differential expression across breast cancer subtypes and have both oncogenic and tumor-suppressive roles. Numerous microarray studies reported different expression patterns of miRNAs in breast cancers and found clinical interest for several miRNAs but often with contradictory results. Aim of this study is to identify miRNAs that are differentially expressed in estrogen receptor positive (ER(+)) and negative (ER(-)) breast primary tumors to better understand the molecular basis for the phenotypic differences between these two sub-types of carcinomas and to find potential clinically relevant miRNAs. METHODS: We used the robust and reproductive tool of quantitative RT-PCR in a large cohort of well-annotated 153 breast cancers with long-term follow-up to identify miRNAs specifically differentially expressed between ER(+) and ER(-) breast cancers. Cytotoxicity tests and transfection experiments were then used to examine the role and the regulation mechanisms of selected miRNAs. RESULTS: We identified a robust collection of 20 miRNAs significantly deregulated in ER(+) compared to ER(-) breast cancers : 12 up-regulated and eight down-regulated miRNAs. MiR-190b retained our attention as it was the miRNA the most strongly over-expressed in ER(+) compared to ER(-) with a fold change upper to 23. It was also significantly up-regulated in ER(+)/Normal breast tissue and down-regulated in ER(-)/Normal breast tissue. Functional experiments showed that miR-190b expression is not directly regulated by estradiol and that miR-190b does not affect breast cancer cell lines proliferation. Expression level of miR-190b impacts metastasis-free and event-free survival independently of ER status. CONCLUSIONS: This study reveals miR-190b as the highest up-regulated miRNA in hormone-dependent breast cancers. Due to its specificity and high expression level, miR-190b could therefore represent a new biomarker in hormone-dependent breast cancers but its exact role carcinogenesis remains to elucidate. PMID- 26141722 TI - Telemedicine in a Dutch intensive care unit: A descriptive study of the first results. AB - INTRODUCTION: Tele-intensive care (teleIC) can be used to increase the level of care in the intensive care unit (ICU) with the tele-intensivist being at a remote site. In this study we describe the implementation and outcomes, including patient and family satisfaction, of the first Dutch teleIC. METHODS: In a retrospective analysis the patient characteristics are described with a focus on patient outcomes and patient and family satisfaction. The teleIC started on 6 December 2010 in an ICU with three beds. Data for all admitted patients were collected from 1 January 2011 through 31 December 2013 from available systems. Severity of disease (APACHE IV) and standardized mortality ratios (SMR) were available over the complete calendar years 2012 and 2013. A prospective self-made survey of patient and family satisfaction was performed over a 14-month period after the implementation of teleIC. RESULTS: In 2012 and 2013, 556 patients were admitted. The number of operating room recovery patients in the ICU declined over time. One hundred and seven patients were transferred to a higher-level ICU (19%). The SMR for non-transferred patients was 0.73 (95% CI (confidence interval) 0.54-0.98) and 0.66 (95% CI (confidence interval) 0.40-1.02) for transferred patients. These numbers are in line with national data. Thirty-six percent of family and 38% of the patients responded to the survey and showed a positive response concerning communication within the tele IC setting. CONCLUSION: Implementation of teleIC in a Dutch situation was successful and showed favourable results in patient outcomes and the satisfaction of patients and family members. PMID- 26141721 TI - Age dependent normal horizontal VOR gain of head impulse test as measured with video-oculography. AB - BACKGROUND: The head impulse test (HIT) is a recognised clinical sign of the high frequency vestibulo-ocular reflex (VOR), which can be quantified with video oculography. This measures the VOR gain as the ratio of angular eye velocity to angular head velocity. Although normative data is available for VOR gain with video-oculography, most normal studies in general include small numbers of subjects and do not include analysis of variation of VOR gain with age. The purpose of our study was to establish normative data across 60 control subjects aged 20 to 80 years to represent a population distribution. METHODS: Sixty control subjects without any current or previous form of brain disorder or vertigo participated in this study and form the basis for future comparison to patients with vestibular lesions. The relationship between the horizontal vestibulo-ocular reflex (HVOR) velocity gain and age was analysed using a mixed regression model with a random effect for subjects. Differences in testing technique were assessed to ensure reliability in results. RESULTS: The mean HVOR velocity gain of 60 normal subjects was 0.97 (SD = 0.09) at 80 ms and 0.94 (SD = 0.10) at 60 ms. The 2 SD lower limit of normal HVOR velocity gain was 0.79 at 80 ms and 0.75 at 60 ms. No HVOR velocity gain fell below 0.76 and 0.65 at 80 ms and 60 ms respectively. The HVOR velocity gain declined by 0.012 and 0.017 per decade as age increased at 80 ms and 60 ms respectively. A non-physiologically high horizontal HVOR velocity gain was found to occur in tests where passive HITs were predictable in direction and time and where target distance was below 0.70 m. CONCLUSIONS: Normative data with respect to HVOR velocity gain decreases slightly with age, but with careful attention to methodology the 2 SD lower limit of normal is relatively robust across a wide age range and into the eighth decade, without requirement for adjustment with age. PMID- 26141723 TI - Aggressive natural killer-cell neoplasm presenting in the marrow: a report of two cases including one with gains of chromosomes 4q and 9p. AB - Aggressive nature killer (NK)-cell neoplasm includes aggressive NK-cell leukemia (ANKL) and extranodal NK/T-cell lymphoma (ENKTL), nasal type. ANKL is rare and is characterized by a systemic neoplastic proliferation of NK-cells, usually with a leukemic presentation. ENKTL is a predominantly extranodal lymphoma, occurring mainly in the upper aerodigestive tract. Both are aggressive neoplasms strongly associated with Epstein-Barr virus (EBV). Here we report two patients with aggressive NK-cells neoplasms localized in the bone marrow (BM) who presented as prolonged fever, anemia, and thrombocytopenia. Both were treated initially as infectious disease. Imaging studies revealed splenomegaly without any nodular lesion or lymphadenopathy. BM examination revealed extensive involvement by EBV positive NK-cells in both cases. Staging workup including nasal examination/biopsy was negative. Both patients passed away in a month. One case showed gains of chromosomes 4q and 9p by array comparative genomic hybridization. Both tumors were diagnostically challenging due to the unusual clinical presentation and absence of leukemic change, tumor mass or lymphadenopathy. Our cases demonstrate that lymphoma should be considered in patients with fever of unknown origin and bone marrow aspiration/biopsy should be performed as early diagnosis and novel therapeutic regimens may benefit these patients. PMID- 26141724 TI - Protocol for the evaluation of a free health insurance card scheme for poor pregnant women in Mbeya region in Tanzania: a controlled-before and after study. AB - BACKGROUND: The use of demand-side financing mechanisms to increase health service utilisation among target groups and enhance service quality is gaining momentum in many low- and middle-income countries. However, there is limited evidence on the effects of such schemes on equity, financial protection, quality of care, and cost-effectiveness. A scheme providing free health insurance cards to poor pregnant women and their households was first introduced in two regions of Tanzania in 2011 and gradually expanded in 2012. METHODS: A controlled before and after study will examine in one district the effect of the scheme on utilization, quality, and cost of healthcare services accessed by poor pregnant women and their households in Tanzania. Data will be collected 4 months before implementation of the scheme and 17 months after the start of implementation from a survey of 24 health facilities, 288 patients exiting consultations and 1500 households of women who delivered in the previous year in one intervention district (Mbarali). 288 observations of provider-client interactions will also be carried out. The same data will be collected from a comparison district in a nearby region. A process evaluation will ascertain how the scheme is implemented in practice and the level of implementation fidelity and potential moderators. The process evaluation will draw from impact evaluation data and from three rounds of data collection at the national, regional, district, facility and community levels. An economic evaluation will measure the cost-effectiveness of the scheme relative to current practice from a societal perspective. DISCUSSION: This evaluation will generate evidence on the impact and cost-effectiveness of targeted health insurance for pregnant women in a low income setting, as well as building a better understanding of the implementation process and challenges for programs of this nature. PMID- 26141725 TI - Tumour biomarkers: diagnostic, prognostic, and predictive. PMID- 26141726 TI - Endovascular versus open repair of ruptured abdominal aortic aneurysm. AB - INTRODUCTION: Endovascular aneurysm repair (EVAR) is a comparatively less invasive technique than open repair (OR). Debate remains with regard to the benefit of EVAR for patients with ruptured abdominal aortic aneurysm (RAAA). We sought to evaluate and report outcomes of EVAR for RAAA in an Irish tertiary vascular referral centre. METHODS: Patients undergoing emergency surgery for ruptured or symptomatic AAA were identified from theatre logbooks and HIPE database. Retrospective chart review was undertaken. Data were exported to IBM SPSS version 21 for statistical analysis with p < 0.05 considered significant. RESULTS: A total of 41 patients underwent surgery for RAAA. The mean age was 74 years old with a range from 55 to 89 years. The majority (n = 25, 61%) were baseline American Society of Anaesthesiology (ASA) grade 3-4. Of these 56% underwent EVAR with the remaining 44% repaired open. Mortality rate in those undergoing emergency EVAR was 34.8%, compared with 38.9% in those undergoing open surgery. This difference was not statistically significant. The mean overall length of stay was 13 days. With regard to prognostic indicators of patient outcome, increasing patient age was noted to be significantly associated with increased mortality (p = 0.013), as was increased ASA score at time of surgery (p = 0.029). CONCLUSIONS: Mortality rates in those undergoing EVAR for RAAA are comparable with those undergoing open repair. Increasing age and ASA score are significant predictors of mortality in patients with RAAA undergoing intervention. PMID- 26141720 TI - Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth. AB - BACKGROUND: Uterine leiomyomas (fibroids) are highly prevalent benign smooth muscle tumors of the uterus. In the USA, the lifetime risk for women developing uterine leiomyomas is estimated as up to 75%. Except for hysterectomy, most therapies or treatments often provide only partial or temporary relief and are not successful in every patient. There is a clear racial disparity in the disease; African-American women are estimated to be three times more likely to develop uterine leiomyomas and generally develop more severe symptoms. There is also familial clustering between first-degree relatives and twins, and multiple inherited syndromes in which fibroid development occurs. Leiomyomas have been described as clonal and hormonally regulated, but despite the healthcare burden imposed by the disease, the etiology of uterine leiomyomas remains largely unknown. The mechanisms involved in their growth are also essentially unknown, which has contributed to the slow progress in development of effective treatment options. METHODS: A comprehensive PubMed search for and critical assessment of articles related to the epidemiological, biological and genetic clues for uterine leiomyoma development was performed. The individual functions of some of the best candidate genes are explained to provide more insight into their biological function and to interconnect and organize genes and pathways in one overarching figure that represents the current state of knowledge about uterine leiomyoma development and growth. RESULTS: In this review, the widely recognized roles of estrogen and progesterone in uterine leiomyoma pathobiology on the basis of clinical and experimental data are presented. This is followed by fundamental aspects and concepts including the possible cellular origin of uterine fibroids. The central themes in the subsequent parts are cytogenetic aberrations in leiomyomas and the racial/ethnic disparities in uterine fibroid biology. Then, the attributes of various in vitro and in vivo, human syndrome, rodent xenograft, naturally mutant, and genetically modified models used to study possible molecular mechanisms of leiomyoma development and growth are described. Particular emphasis is placed on known links to fibrosis, hypertrophy, and hyperplasia and genes that are potentially important in these processes. CONCLUSIONS: Menstrual cycle-related injury and repair and coinciding hormonal cycling appears to affect myometrial stem cells that, at a certain stage of fibroid development, often obtain cytogenetic aberrations and mutations of Mediator complex subunit 12 (MED12). Mammalian target of rapamycin (mTOR), a master regulator of proliferation, is activated in many of these tumors, possibly by mechanisms that are similar to some human fibrosis syndromes and/or by mutation of upstream tumor suppressor genes. Animal models of the disease support some of these dysregulated pathways in fibroid etiology or pathogenesis, but none are definitive. All of this suggests that there are likely several key mechanisms involved in the disease that, in addition to increasing the complexity of uterine fibroid pathobiology, offer possible approaches for patient-specific therapies. A final model that incorporates many of these reported mechanisms is presented with a discussion of their implications for leiomyoma clinical practice. PMID- 26141727 TI - Evidence of Bos javanicus x Bos indicus hybridization and major QTLs for birth weight in Indonesian Peranakan Ongole cattle. AB - BACKGROUND: Peranakan Ongole (PO) is a major Indonesian Bos indicus breed that derives from animals imported from India in the late 19(th) century. Early imports were followed by hybridization with the Bos javanicus subspecies of cattle. Here, we used genomic data to partition the ancestry components of PO cattle and map loci implicated in birth weight. RESULTS: We found that B. javanicus contributes about 6-7% to the average breed composition of PO cattle. Only two nearly fixed B. javanicus haplotypes were identified, suggesting that most of the B. javanicus variants are segregating under drift or by the action of balancing selection. The zebu component of the PO genome was estimated to derive from at least two distinct ancestral pools. Additionally, well-known loci underlying body size in other beef cattle breeds, such as the PLAG1 region on chromosome 14, were found to also affect birth weight in PO cattle. CONCLUSIONS: This study is the first attempt to characterize PO at the genome level, and contributes evidence of successful, stabilized B. indicus x B. javanicus hybridization. Additionally, previously described loci implicated in body size in worldwide beef cattle breeds also affect birth weight in PO cattle. PMID- 26141729 TI - Determinants of loss to follow-up in patients on antiretroviral treatment, South Africa, 2004-2012: a cohort study. AB - BACKGROUND: The number of Human Immunodeficiency Virus (HIV) infected people eligible for initiation on antiretroviral Therapy (ART) is increasing. ART programmatic success requires that patients who are taking ART remain on treatment and are followed up regularly. This study investigated factors associated with being lost to follow-up, in a cohort of patients enrolled in a pharmacovigilance study in South Africa. METHODS: This was a retrospective observational cohort study performed at one of the Medunsa National Pharmacovigilance Centre's (MNPC) ART sentinel surveillance sites. Loss to Follow up (LTFU) was defined as "a patient who had been followed up at the sentinel site, who had not had contact with the health facility for 180 days or more since their last recorded expected date of return or if there were 180 days or more between the expected date of return and the next clinic visit". RESULTS: Out of 595 patients, 65.5% (n = 390) were female and 23.4% (n = 139) were LTFU. The median time on ART before LTFU was 21.5 months (interquartile range: 12.9 - 34.7 months). The incidence rate of LTFU was 103 per 1000 person-years in the first year on ART and increased to 405 per 1000 person-years in the eighth year of taking ART. Factors associated with becoming LTFU included not having a committed partner (Adjusted Hazard Ratio (aHR): 2.9, 95% Confidence Interval (CI):1.19 6.97, p = 0.019), being self-employed (aHR: 13.9, 95% CI:2.81 - 69.06, p = 0.001), baseline CD4 count > 200 cells/ml (aHR: 3.8, 95% CI: 1.85-7.85, p < 0.001), detectable last known Viral Load (VL) (aHR: 3.6, 95% CI:1.98-6.52, p < 0.001) and a last known World Health Organisation clinical stage three or four (aHR: 2.0, 95% CI:1.22-3.27, p = 0.006). Patients that previously had an ART adverse event had a lower risk (aHR: 0.6, 95% CI: 0.38 - 0.99, p = 0.044) of becoming LTFU than those that had not. CONCLUSION: The incidence rate of LTFU increases with additional years on ART. Intensified measures to improve patient retention on ART must be prioritised with increasing patient time on ART and in patients that are at increased risk of becoming lost to follow-up. PMID- 26141728 TI - Impact of amyloid beta aggregate maturation on antibody treatment in APP23 mice. AB - INTRODUCTION: The deposition of the amyloid beta protein (Abeta) in the brain is a hallmark of Alzheimer's disease (AD). Removal of Abeta by Abeta-antibody treatment has been developed as a potential treatment strategy against AD. First clinical trials showed neither a stop nor a reduction of disease progression. Recently, we have shown that the formation of soluble and insoluble Abeta aggregates in the human brain follows a hierarchical sequence of three biochemical maturation stages (B-Abeta stages). To test the impact of the B-Abeta stage on Abeta immunotherapy, we treated transgenic mice expressing human amyloid precursor protein (APP) carrying the Swedish mutation (KM670/671NL; APP23) with the Abeta-antibody beta1 or phosphate-buffered saline (PBS) beginning 1) at 3 months, before the onset of dendrite degeneration and plaque deposition, and 2) at 7 months, after the start of Abeta plaque deposition and dendrite degeneration. RESULTS: At 5 months of age, first Abeta aggregates in APP23 brain consisted of non-modified Abeta (representing B-Abeta stage 1) whereas mature Abeta-aggregates containing N-terminal truncated, pyroglutamate-modified AbetaN3pE and phosphorylated Abeta (representing B-Abeta stage 3) were found at 11 months of age in both beta1- and PBS-treated animals. Protective effects on commissural neurons with highly ramified dendritic trees were observed only in 3 month-old beta1-treated animals sacrificed at 5 months. When treatment started at 7 months of age, no differences in the numbers of healthy commissural neurons were observed between beta1- and PBS-treated APP23 mice sacrificed with 11 months. CONCLUSIONS: Abeta antibody treatment was capable of protecting neurons from dendritic degeneration as long as Abeta aggregation was absent or represented B-Abeta stage 1 but had no protective or curative effect in later stages with mature Abeta aggregates (B-Abeta stage 3). These data indicate that the maturation stage of Abeta aggregates has impact on potential treatment effects in APP23 mice. PMID- 26141730 TI - A rapid assay for Hendra virus IgG antibody detection and its titre estimation using magnetic nanoparticles and phycoerythrin. AB - Detection of Hendra viral IgG antibody in animal sera is useful for surveillance following a virus outbreak. The commonly used enzyme-linked immunosorbent assay and fluorescence-based Luminex assay typically consist of three steps and take at least several hours to complete. We have simplified the procedure to two steps in an effort to develop a rapid procedure for IgG antibody, but not IgM antibody, detection. This is achieved by conjugating the fluorescence label R-phycoerythrin directly onto the IgG binding protein Protein G. The use of magnetic nanoparticles, due to their large specific surface area, has helped reduce each of the binding steps to 20 min. As a result, the whole assay can be completed in 60 min. We also demonstrate a method to quickly estimate IgG antibody titres by assaying the sera at only two dilutions (i.e. 1:20 and 1:1000) and using the fluorescence ratio at these dilutions as an indicator of antibody titre. The results of this approach correlated well with the well-regarded serum neutralization test in virus antibody assays. This protocol reported here can be adopted in Luminex assays, fluorescence-linked immunosorbent assays and assays on microfluidics platforms for rapid antibody surveillance of Hendra and other viruses. PMID- 26141731 TI - Development of a protocol for the identification of tospoviruses and thrips species in individual thrips. AB - A protocol for identifying tospovirus and thrips species in an individual thrips sample was successfully developed. First, an individual thrips was soaked in an RNA stabilization solution to preserve protein and nucleic acids and ground in a carbonate buffer containing 0.2% sodium diethyldithiocarbamate. Initially, the thrips extracts were screened for tospovirus infection by dot blot analysis using antibodies to nucleocapsid (N) proteins of tospoviruses. Thrips extracts with positive results by dot blot analysis were further subjected to RNA extraction. Next, tospovirus species were identified by reverse transcription-polymerase chain reaction (RT-PCR) using species-specific primers for the N genes of four tospoviruses known to occur in Thailand, including Capsicum chlorosis virus (CaCV), Melon yellow spot virus (MYSV), Tomato necrotic ringspot virus (TNRV) and Watermelon silver mottle virus (WSMoV). The residual genomic DNA in the thrips RNA extract was used as a template to identify thrips species by PCR with species specific primers to the internal transcribed spacer 2 regions of the rRNA of Ceratothripoides claratris, Frankliniella intonsa, Scirtothrips dorsalis and Thrips palmi. This protocol was initially validated against laboratory-reared thrips and then used to determine the occurrence of viruliferous thrips species collected from tomato, pepper, watermelon and cucumber fields in Thailand. PMID- 26141732 TI - Development and clinical evaluation of a new gold-immunochromatographic assay for the detection of antibodies against field strains of pseudorabies virus. AB - An immunochromatographic strip (ICS) was developed for the detection of swine antibodies against glycoprotein E (gE) in Pseudorabies Virus (PRV). In this test, Staphylococcal Protein A (SPA) labeled with colloidal gold was dispensed on a conjugate pad as the detector. Purified PRV-gE and pig-IgG were blotted on a nitrocellulose membrane for the test (T) and control lines (C), respectively. If the tested serum contains IgG antibodies against PRV-gE, the IgG will interact with the colloidal gold-SPA to form a complex (gold-SPA-swine IgG). The complex will react with the immobilized PRV-gE on the T line and the Pig-IgG in the C line of the ICS to form two visible red bands. If there is no IgG antibody against PRV-gE in the sample serum, only the C line will be visible. The ICS was capable of specifically detecting PRV-gE antibody within 5 min, and its stability and reproducibility were quite good after storage at 4 degrees C and use within 4 months. Using an IDEXX Pseudorabies Virus gE Antibody Test Kit (IDEXX PRV gE Ab test) as a reference, the relative specificity and sensitivity of the ICS were determined to be 81.6% and 90.7%, respectively. Furthermore, there was a good agreement between the results obtained by the commercial product and the ICS (kappa=0.7289). PMID- 26141733 TI - Antioxidative responses of Pseudomonas fluorescens YZ2 to simultaneous exposure of Zn and Cefradine. AB - Binary pollution of both heavy metals and antibiotics has received increasing attentions for their joint effects of eco-toxicity and health hazards. To reveal the effects of mixtures of different pollutants on bacterial antioxidant response system, Pseudomonas fluorescens ZY2, a new strain isolated from swine wastewater, was chosen to determinate growth (bacterial density OD600), reactive oxygen species (ROS) concentration, protein concentration and superoxide dismutase (SOD) activity under exposure treatments of Zn, Cefradine or Zn + Cefradine. Bacterial densities of all the treatment groups increased significantly over the incubation time, but those containing pollutant addition were slightly lower than the control at different times of incubation. Both ROS concentration and SOD activity increased first and then decreased (p < 0.01) over time, which was opposite to the protein concentrations (p < 0.01), showing a much significant increase by Cefradine alone. With Zn concentration increasing from 40 to 160 mg/L, the intracellular SOD activity increased as a response to the improvement of ROS (p < 0.05), while the balance between ROS and SOD was broken down due to the disproportionate change of total SOD activity and ROS concentration, the bacterial densities therefore decreased for the weak resistance. With the combined treatment of Zn (200 mg/L) and Cefradine (1 mg/L), though the toxicity of Zn caused a much significant increase of ROS, the bacterial resistance was further improved showing a more significant increase of total SOD activity and the bacterial densities therefore increased bacterial growth. Zn concentration also affected the protein synthesis. Either single or binary stress induced the bacterial resistance by regulating SOD activity to eliminate ROS. All results of the bacterial oxidant stress, SOD response and protein synthesis in the combined treatment groups were more complicated than those in single treatment groups, which depended on the properties of the single treatment as well as the interaction between the two treatments upon bacterial activity. For P. fluorescens ZY2, the mediation of SOD activity to eliminate ROS in response to the combined exposure to Zn and Cefradine was first revealed as one of the co resistance mechanisms, which is informative to further understanding the risk of antibiotics resistant bacteria to human and environmental health more accurately. PMID- 26141734 TI - A painful hand after a fall. PMID- 26141735 TI - The clinical impact of implementing the Roche(r) bilirubin total Gen.3 method on neonate phototherapy. AB - OBJECTIVE: To predict the impact of implementing the Roche(r) Gen.3 bilirubin total method on the number of bilirubin results that would trigger phototherapy using the phototherapy nomogram published in the Canadian Paediatric Society (CPS) Guidelines for Treatment of Hyperbilirubinemia. DESIGN AND METHODS: BILTS method results (N=563) were obtained on the Roche(r) C501 analyzer and the corresponding Bilirubin Total Gen.3 assay results were derived by linear regression. Total bilirubin results, gestational age and postnatal age were plotted with the CPS phototherapy nomogram to determine if phototherapy was indicated with both the BILTS and Gen.3 methods. Clinical thresholds for phototherapy using the BILTS and new Gen.3 methods were compared by Pearson's chi square test. RESULTS: 284 bilirubin results obtained from infants 35-37 weeks gestation (n=157 neonates) and 279 results from term infants >38 weeks gestation (n=224 neonates) were interpreted with the CPS phototherapy nomogram as either with or without risk factors. Use of the Gen.3 assay reduced the number of bilirubin results that would meet the high-risk threshold line to initiate phototherapy by 7% (p<=0.05) for 35-37 week gestation infants and would reduce phototherapy by 6% (p<=0.05) for >38 week gestation infants with the medium-risk threshold line compared to when the BILTS method was used. CONCLUSIONS: Replacement of the BILTS method by the Gen.3 bilirubin method is anticipated to be associated with a 7% decrease in the number of neonate results that would meet phototherapy thresholds. It cannot be determined if the BILTS assay was associated with a 7% over-treatment or the Gen.3 assay will be associated with 7% under-treatment. While standardization of bilirubin assays remains elusive, nomograms based on bilirubin methods will remain susceptible to method-biases and patient care decisions will remain subject to this uncertainty. PMID- 26141736 TI - HPLC method for urinary theobromine determination: Effect of consumption of cocoa products on theobromine urinary excretion in children. AB - OBJECTIVE: To validate a simple method of urinary theobromine determination, to assess urinary theobromine levels in 80 healthy children and to relate these levels to consumption of cocoa products. DESIGN AND METHODS: Urine samples were diluted, directly injected into an HPLC system, separated by gradient elution on a C18 column, and detected by UV spectrometry. The method was validated for linearity, limits of detection and quantification, imprecision, accuracy, recovery and interferences. The proposed method was used to assess 12-h day and 12-h night urinary theobromine excretion by 80 healthy children, divided into four groups based on consumption of cocoa products. In addition, urinary excretion of magnesium and oxalate, also present in cocoa, was measured in these four groups. RESULTS: The method was linear to a theobromine concentration of 278MUmol/L (50mg/L). LOD and LOQ for urine samples, diluted 1:5 (vol/vol) with water, were 1.1 and 3.6MUmol/L respectively. Within-run and between-run imprecisions (CV) were each <2%. Average recovery was 99%, and analysis of a certified reference sample showed an error <2.5%. Theobromine excretion levels were significantly higher in healthy children with higher consumption of cocoa products (p<0.001), but oxalate (p=0.098) and magnesium (p=0.068) excretion levels did not differ significantly. CONCLUSION: This validated method resulted in urinary theobromine determination with 100% recovery, without sample pretreatment. Urinary theobromine levels in healthy children were directly related to their consumption of cocoa products. PMID- 26141737 TI - Overexpression of mutant HSP27 causes axonal neuropathy in mice. AB - BACKGROUND: Mutations in heat shock 27 kDa protein 1 (HSP27 or HSPB1) cause distal hereditary motor neuropathy (dHMN) or Charcot-Marie-Tooth disease type 2 F (CMT2F) according to unknown factors. Mutant HSP27 proteins affect axonal transport by reducing acetylated tubulin. RESULTS: We generated a transgenic mouse model overexpressing HSP27-S135F mutant protein driven by Cytomegalovirus (CMV) immediate early promoter. The mouse phenotype was similar to dHMN patients in that they exhibit motor neuropathy. To determine the phenotypic aberration of transgenic mice, behavior test, magnetic resonance imaging (MRI), electrophysiological study, and pathology were performed. Rotarod test showed that founder mice exhibited lowered motor performance. MRI also revealed marked fatty infiltration in the anterior and posterior compartments at calf level. Electrophysiologically, compound muscle action potential (CMAP) but not motor nerve conduction velocity (MNCV) was reduced in the transgenic mice. Toluidine staining with semi-thin section of sciatic nerve showed the ratio of large myelinated axon fiber was reduced, which might cause reduced locomotion in the transgenic mice. Electron microscopy also revealed abundant aberrant myelination. Immunohistochemically, neuronal dysfunctions included elevated level of phosphorylated neurofilament and reduced level of acetylated tubulin in the sural nerve of transgenic mice. There was no additional phenotype besides motor neuronal defects. CONCLUSIONS: Overexpression of HSP27-S135F protein causes peripheral neuropathy. The mouse model can be applied to future development of therapeutic strategies for dHMN or CMT2F. PMID- 26141739 TI - Glatiramer acetate-induced hepatitis in a patient with multiple sclerosis. PMID- 26141738 TI - Transcript analysis of laser capture microdissected white matter astrocytes and higher phenol sulfotransferase 1A1 expression during autoimmune neuroinflammation. AB - BACKGROUND: Astrocytes, the most abundant cell population in mammal central nervous system (CNS), contribute to a variety of functions including homeostasis, metabolism, synapse formation, and myelin maintenance. White matter (WM) reactive astrocytes are important players in amplifying autoimmune demyelination and may exhibit different changes in transcriptome profiles and cell function in a disease-context dependent manner. However, their transcriptomic profile has not yet been defined because they are difficult to purify, compared to gray matter astrocytes. Here, we isolated WM astrocytes by laser capture microdissection (LCM) in a murine model of multiple sclerosis to better define their molecular profile focusing on selected genes related to inflammation. Based on previous data indicating anti-inflammatory effects of estrogen only at high nanomolar doses, we also examined mRNA expression for enzymes involved in steroid inactivation. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL6 mice with MOG35-55 immunization. Fluorescence activated cell sorting (FACS) analysis of a portion of individual spinal cords at peak disease was used to assess the composition of immune cell infiltrates. Using custom Taqman low-density-array (TLDA), we analyzed mRNA expression of 40 selected genes from immuno-labeled laser-microdissected WM astrocytes from lumbar spinal cord sections of EAE and control mice. Immunohistochemistry and double immunofluorescence on control and EAE mouse spinal cord sections were used to confirm protein expression in astrocytes. RESULTS: The spinal cords of EAE mice were infiltrated mostly by effector/memory T CD4+ cells and macrophages. TLDA based profiling of LCM-astrocytes identified EAE-induced gene expression of cytokines and chemokines as well as inflammatory mediators recently described in gray matter reactive astrocytes in other murine CNS disease models. Strikingly, SULT1A1, but not other members of the sulfotransferase family, was expressed in WM spinal cord astrocytes. Moreover, its expression was further increased in EAE. Immunohistochemistry on spinal cord tissues confirmed preferential expression of this enzyme in WM astrocytic processes but not in gray matter astrocytes. CONCLUSIONS: We described here for the first time the mRNA expression of several genes in WM astrocytes in a mouse model of multiple sclerosis. Besides expected pro-inflammatory chemokines and specific inflammatory mediators increased during EAE, we evidenced relative high astrocytic expression of the cytoplasmic enzyme SULT1A1. As the sulfonation activity of SULT1A1 inactivates estradiol among other phenolic substrates, its high astrocytic expression may account for the relative resistance of this cell population to the anti-neuroinflammatory effects of estradiol. Blocking the activity of this enzyme during neuroinflammation may thus help the injured CNS to maintain the anti-inflammatory activity of endogenous estrogens or limit the dose of estrogen co-regimens for therapeutical purposes. PMID- 26141740 TI - Near-patient tests and the clinical gaze in decision-making of Swedish GPs not following current guidelines for sore throat - a qualitative interview study. AB - BACKGROUND: Excessive antibiotics use increases the risk of resistance. Previous studies have shown that the Centor score combined with Rapid Antigen Detection Test (RADT) for Group A Streptococci can reduce unnecessary antibiotic prescribing in patients with sore throat. According to the former Swedish guidelines RADT was recommended with 2-4 Centor criteria present and antibiotics were recommended if the test was positive. C- reactive protein (CRP) was not recommended for sore throats. Inappropriate use of RADT and CRP has been reported in several studies. METHODS: From a larger project 16 general practitioners (GPs) who stated management of sore throats not according to the guidelines were identified. Half-hour long semi-structured interviews were conducted. The topics were the management of sore throats and the use of near-patient tests. Qualitative content analysis was used. RESULTS: The use of the near-patient test interplayed with the clinical assessment and the perception that all infections caused by bacteria should be treated with antibiotics. The GPs expressed a belief that the clinical picture was sufficient for diagnosis in typical cases. RADT was not believed to be relevant since it detects only one bacterium, while CRP was considered as a reliable numerical measure of bacterial infection. CONCLUSIONS: Inappropriate use of near-patient test can partly be understood as remnants of outdated knowledge. When new guidelines are introduced the differences between them and the former need to be discussed more explicitly. PMID- 26141742 TI - Abstracts from the Seventeenth Annual Education Conference of the National Society of Genetic Counselors (Denver, Colorado, October 1998). PMID- 26141741 TI - [Depression in cancer patients]. AB - Cancer patients often suffer from major depression or depressive syndromes. Although it is well known that depressive symptoms can appear at any time during the course of an oncological disease, certain periods for instance time after diagnosis carry a higher risk. Reported prevalence rates differ widely (up to 60%), reflecting also diagnostic difficulties. Oncologists recognize depression in their patients only in 15 to 50% and the percentage of patients who receive adequate therapy is even lower. Consequently, this leads to a reduced quality of life. Furthermore, impaired compliance/adherence and consequently a poorer prognosis of the oncological disease are discussed in this context. It should be also emphasized, that concomitant depression increases the risk of suicide in cancer patients. Although the number of clinical trials using either psychotherapy or antidepressant medication for the therapy of depression in cancer patients is limited, good therapeutic options are available. PMID- 26141744 TI - Stereotactic Needle Biopsy: Sharpening the Tip. PMID- 26141743 TI - Alpha-crystallin-derived peptides as therapeutic chaperones. AB - BACKGROUND: The demonstration of chaperone-like activity in peptides (mini chaperones) derived from alpha-crystallin's chaperone region has generated significant interest in exploring the therapeutic potential of peptide chaperones in diseases of protein aggregation. Recent studies in experimental animals show that mini-chaperones could reach intended targets and alter the disease phenotype. Although mini-chaperones show potential benefits against protein aggregation diseases, they do tend to form aggregates on storage. There is thus a need to fine-tune peptide chaperones to increase their solubility, pharmacokinetics, and biological efficacy. SCOPE OF REVIEW: This review summarizes the properties and the potential therapeutic roles of mini-chaperones in protein aggregation diseases and highlights some of the refinements needed to increase the stability and biological efficacy of mini-chaperones while maintaining or enhancing their chaperone-like activity against precipitation of unfolding proteins. MAJOR CONCLUSIONS: Mini-chaperones suppress the aggregation of proteins, block amyloid fibril formation, stabilize mutant proteins, sequester metal ions, and exhibit antiapoptotic properties. Much work must be done to fine tune mini-chaperones and increase their stability and biological efficacy. Peptide chaperones could have a great therapeutic value in diseases associated with protein aggregation and apoptosis. GENERAL SIGNIFICANCE: Accumulation of misfolded proteins is a primary cause for many age-related diseases, including cataract, macular degeneration, and various neurological diseases. Stabilization of native proteins is a logical therapeutic approach for such diseases. Mini chaperones, with their inherent antiaggregation and antiapoptotic properties, may represent an effective therapeutic molecule to prevent the cascade of protein conformational disorders. Future studies will further uncover the therapeutic potential of mini-chaperones. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. PMID- 26141745 TI - Futility and Human Endeavor: the Treatment of Cerebral Metastases. PMID- 26141746 TI - Considerations When Contemplating Minimally Invasive Versus Open Transforaminal Lumbar Interbody Fusion. PMID- 26141747 TI - Feed efficiency, blood parameters, and ingestive behavior of young Nellore males and females. AB - This study aimed to evaluate differences in efficiency of feed utilization between young Nellore males and females by comparing growth traits, feed intake, blood parameters, and ingestive behavior of the animals. Data from 768 Nellore males and females that participated in eight performance tests for individual feed intake evaluation were used. Performance and feed efficiency measures, efficiency-related hematological, metabolic and hormonal variables, and data regarding ingestive behavior were collected. Feed efficiency measures were defined by the relationship between performance and feed intake. Data were analyzed using mixed models that included the fixed effects of sex, herd, and the covariate age within sex and the random effects of facility within year, year, and residual. Significant differences between males and females were observed for traits related to weight gain and feed intake. Although individual dynamics of feed efficiency measures differed between males and females, no significant differences in residual feed intake, feed efficiency, or relative growth rate were observed between sexes. Significant differences between sexes were found for platelets, red blood cells, hemoglobin, creatinine, glucose, urea, triglycerides, insulin, cortisol, and IGF-I. Females spent more time feeding and less time ruminating when compared to males. However, males exhibited higher feeding efficiency and lower rumination efficiency than females. Growing Nellore males and females are efficient in feed utilization, and the differences in blood variables observed are probably due to differences in body size and feed intake. Males spend less time eating, consume more food, and spend more time ruminating than females. PMID- 26141749 TI - Breaking news: Can the media make you sick? PMID- 26141748 TI - Variations of BRAF mutant allele percentage in melanomas. AB - BACKGROUND: BRAF mutations are present in 40% of human skin melanomas. Mutated tumors with an increased percentage of BRAF mutant alleles (BRAF-M%) may have a better response to RAF/MEK inhibitors. We evaluated the BRAF-M% in melanomas, and the genetic causes of its variation. METHODS: BRAF-M% was quantified by pyrosequencing, real-time PCR (rtPCR) and/or picoliter-droplet PCR (dPCR). BRAF mutant expression was detected by immunohistochemistry. Chromosomal alterations were analyzed with fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) arrays. RESULTS: BRAF-M% quantification obtained with pyrosequencing was highly correlated (R = 0.94) with rtPCR, and with dPCR. BRAF-M% quantified from DNA and RNA were also highly correlated (R = 0.98). Among 368 samples with >80% tumor cells, 38.6% had a BRAF (V600E) mutation. Only 66.2% cases were heterozygous (BRAF-M% 30 to 60%). Increased BRAF-M% (>60%) was observed in 19% of cases. FISH showed a polysomy of chromosome 7 in 13.6%, 35.3% and 54.5% of BRAF wild-type, heterozygous and non-heterozygous BRAF-mutated samples, respectively (P < 0.005). Amplification (5.6%) and loss (3.2%) of BRAF locus were rare. By contrast, chromosome 7 was disomic in 27/27 BRAF-mutated nevi. CONCLUSIONS: BRAF-M% is heterogeneous and frequently increased in BRAF mutant melanomas. Aneuploidy of chromosome 7 is more frequent in BRAF mutant melanomas, specifically in those with high BRAF-M%. PMID- 26141750 TI - A scoping study of cultural interventions to treat addictions in Indigenous populations: methods, strategies and insights from a Two-Eyed Seeing approach. AB - BACKGROUND: This paper describes the methods, strategies and insights gained from a scoping study using a "Two-Eyed Seeing" approach. An evolving technique, Two Eyed Seeing respects and integrates the strengths of Indigenous knowledge and Western sciences, often "weaving back and forth" between the two worldviews. The scoping study was used to inform a tool for measuring the impact of culturally based addictions treatment services on wellness in Indigenous populations. It formed part of a three-year study, Honouring Our Strengths: Indigenous Culture as Intervention in Addictions Treatment. The scoping study identified and mapped literature on cultural interventions in addictions treatment, and described the nature, extent and gaps in literature. METHODS: Using a Two-Eyed Seeing approach, we adapted, applied and enhanced a common framework of scoping studies. In the end stage of the scoping review process, an Ad Hoc Review Group, led by our project Elder, reviewed and interpreted Indigenous and Western understandings within the mapped information. Elements of the scoping study were joined with results from community focus groups with staff at treatment centres. RESULTS: Two Eyed Seeing contributed differently at each stage of the scoping study. In early stages, it clarified team expertise and potential contributions. At the mid point, it influenced our shift from a systematic to a scoping review. Near the end, it incorporated Western and Indigenous knowledge to interpret and synthesize evidence from multiple sources. CONCLUSIONS: This paper adds to the collective work on augmenting the methodology of scoping studies. Despite the challenges of a Two-Eyed Seeing approach, it enables researchers using scoping studies to develop knowledge that is better able to translate into meaningful findings for Indigenous communities. PMID- 26141751 TI - Spotted fever group rickettsiae detected in immature stages of ticks parasitizing on Iberian endemic lizard Lacerta schreiberi Bedriaga, 1878. AB - Spotted fever rickettsioses are tick-borne diseases of growing public health concern. The prevalence of rickettsia-infected ticks and their ability to parasitize humans significantly influence the risk of human infection. Altogether 466 Ixodes ricinus ticks (428 nymphs and 38 larvae) collected from 73 Lacerta schreiberi lizards were examined by PCR targeting the citrate synthetase gene gltA for the presence of Rickettsia spp. Rickettsial DNA was detected in 47% of nymphs and 31.6% of larvae. They were subsequently subjected to a second PCR reaction using primers derived from the outer membrane protein rOmpA encoding gene (ompA) to detect spotted fever group rickettsiae (SFG). This analysis shows that 41.4% of nymphs and 7.9% of larvae collected from the lizards contain DNA of SFG rickettsiae. Sequencing of 43 randomly selected samples revealed two different haplotypes, both closely related to R. monacensis (39 and 4 samples, respectively). The remaining ompA negative Rickettsia spp. samples were determined to be R. helvetica based on sequencing of ompB and gltA fragments. Our results indicate that the role of Iberian endemic lizard L. schreiberi and its ectoparasites in the ecology and epidemiology of zoonotic SFG rickettsioses may be appreciable. PMID- 26141752 TI - The administration of nasal drops in the "Kaiteki" position allows for delivery of the drug to the olfactory cleft: a pilot study in healthy subjects. AB - Systemic treatment with corticosteroids shows therapeutic effects, few patients benefit from intranasal topical drug application, probably due to limited access of the drug to the olfactory epithelium. The aim of the present study was to investigate how drops distribute within the nasal cavity when the "Kaiteki" position is performed. Thirteen healthy volunteers participated. Subjects were lying on the side with the head tilted and the chin turned upward. Blue liquid was used to visualize the intranasal distribution of the nasal drops. The investigation was carried out using photo documentation thorough nasal endoscopy; the intranasal distribution of the dye was judged by two independent observers in both a decongested state and a natural state where no decongestants had been used. With regard to the main criterion of this study, using the "Kaiteki" position, nasal drops reached the olfactory cleft in 96 % of the decongested cases and 75 % of the cases who had not been decongested. However, this difference was not statistically different. Because the "Kaiteki" maneuver is not too difficult to perform, it is more likely that topical steroids can be helpful in cases of olfactory loss. PMID- 26141753 TI - Parathyroid function following total thyroidectomy using energy devices. AB - LigaSure precise (LP) and harmonic scalpel (HS) are two energy-based devices used in thyroidectomy surgery. We aimed to compare the effect of these two devices in patients who had undergone total thyroidectomy, by highlighting the post operative parathyroid function. A total of 201 consecutive patients for whom total thyroidectomy had been planned were prospectively classified into two groups. There were 104 patients in LP group and 97 patients in HS group. Hypoparathyroidism was followed up by serially measuring the levels of intact parathyroid hormone (iPTH) and serum calcium. The early iPTH level was 29 (8-50) pg/mL in group LP, and 17 (4-43) pg/mL in group HS. The early iPTH level was significantly lower in the HS group (p < 0.001). However, these levels were within the reference interval in both groups. The early iPTH level was lower than 20 pg/mL in 23 (23.1 %) patients in HS group, and 15 (13.7 %) patients in LP group (p < 0.001). Also, the late iPTH levels were not statistically significance between two groups. The early and late serum calcium levels were not statistically significant between groups. However, the amount of calcium replacement was higher in the HS group than the LP group and the duration of treatment was longer in the HS group than the LP group (p < 0.05). In conclusion, although parathyroid hormone levels impaired in the HS group more than LP group in the early period, these levels were in the normal limits in both groups. These levels were not significant between groups in the long time period. PMID- 26141754 TI - Purification and partial characterization of a ribosome-inactivating protein from the latex of Euphorbia trigona Miller with cytotoxic activity toward human cancer cell lines. AB - BACKGROUND: The objective of this study is to investigate the cytotoxic activity of three isolectins purified from the latex of Euphorbia trigona Miller. HYPOTHESIS: Among lectins are the ribosome-inactivating proteins (RIPs), which are potent inhibitors of protein synthesis in cells and in cell-free systems. RESULTS: Three isolectins, ETR1, ETR2 and ETR3, were purified by anion exchange chromatography. Both ETR1 and ETR3 yielded a single band on SDS-PAGE under reducing conditions, corresponding to a molecular weight of 32 g mol(-1), while ETR2 yielded two bands corresponding to 31 and 33 g mol(-1). When non-reducing conditions were used molecular weight decreased, indicating the presence of intrachain disulfide bonds. Size-exclusion chromatography revealed proteins of apparent molecular weight of 59-63 g mol(-1), suggesting a dimeric nature, with subunits not being held together by disulfide linkage. ETR1, ETR2 and ETR3 hemagglutinated human, sheep and rat erythrocytes and this hemagglutination was specifically inhibited by galactose and its derivatives. The lectins studied were thermostable up to 60 degrees C and their observed activity was maintained across pH range 5-12. These lectins, from the latex of Euphorbia trigona, are potent inhibitors of eukaryotic protein synthesis in a cell-free system. Flow cytometry analysis revealed the antiproliferative activity of them toward A549, HeLa, H116, HL-60 cell lines. CONCLUSION: Euphorbia trigona isolectins are RIPs with cytotoxic activity toward human cancer cell lines. PMID- 26141755 TI - Modulation by geraniol of gene expression involved in lipid metabolism leading to a reduction of serum-cholesterol and triglyceride levels. AB - BACKGROUND: Geraniol (G) is a natural isoprenoid present in the essential oils of several aromatic plants, with various biochemical and pharmacologic properties. Nevertheless, the mechanisms of action of G on cellular metabolism are largely unknown. HYPOTHESIS/PURPOSE: We propose that G could be a potential agent for the treatment of hyperlipidemia that could contribute to the prevention of cardiovascular disease. The aim of the present study was to advance our understanding of its mechanism of action on cholesterol and TG metabolism. STUDY DESIGN/METHODS: NIH mice received supplemented diets containing 25, 50, and 75 mmol G/kg chow. After a 3-week treatment, serum total-cholesterol and triglyceride levels were measured by commercial kits and lipid biosynthesis determined by the [(14)C] acetate incorporated into fatty acids plus nonsaponifiable and total hepatic lipids of the mice. The activity of the mRNA encoding HMGCR-the rate-limiting step in cholesterol biosynthesis-along with the enzyme levels and catalysis were assessed by real-time RT-PCR, Western blotting, and HMG-CoA-conversion assays, respectively. In-silico analysis of several genes involved in lipid metabolism and regulated by G in cultured cells was also performed. Finally, the mRNA levels encoded by the genes for the low-density lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by real-time RT-PCR. RESULTS: Plasma total-cholesterol and triglyceride levels plus hepatic fatty-acid, total lipid, and nonsaponifiable-lipid biosynthesis were significantly reduced by feeding with G. Even though an up-regulation of the mRNA encoding HMGCR occurred in the G treated mouse livers, the protein levels and specific activity of the enzyme were both inhibited. G also enhanced the mRNAs encoding the LDL and VLDL receptors and reduced ACACA mRNA, without altering the transcription of the mRNA encoding the SREBF2. CONCLUSIONS: The following mechanisms may have mediated the decrease in plasma lipids levels in mice: a down-regulation of hepatocyte cholesterol synthesis occurred as a result of decreased HMGCR protein levels and catalytic activity; the levels of LDLR mRNA became elevated, thus suggesting an increase in the uptake of serum LDL, especially by the liver; and TG synthesis became reduced very likely because of a decrease in fatty-acid synthesis. PMID- 26141756 TI - The effect of angoroside C on pressure overload-induced ventricular remodeling in rats. AB - BACKGROUND: Our previous study reveals that total rough extract of Radix Scrophulariae has a beneficial effect on ventricular remodeling. HYPOTHESIS: After carrying out a series of preliminary experiments, we speculated that angoroside C may be the effective agent. STUDY DESIGN: After oral administration, the effect of angoroside C on ventricular remodeling was evaluated by using a pressure-overloaded rat model, some related indexes were detected in vivo. METHODS: A model of pressure overloaded ventricular remodeling was produced by abdominal aortic constriction (AAC) in rats. The sham-operated rats underwent an identical surgical procedure except for AAC. AAC rats were randomly divided into five groups: model control group, three angoroside C treated groups (7.5, 15 and 30 mg.kg(-1)) and captopril treated group (40 mg.kg(-1)). The rats were orally administered with the corresponding drugs or drinking water for 4 weeks. The levels of blood pressure (BP), left ventricular weight index (LVWI) and heart weight index (HWI) were detected. Myocardium tissue was stained with hematoxylin and eosin or picric acid/sirius red for cardiomyocyte cross-section area or collagen content measurements respectively. The concentrations of angiotensin II (Ang II), hydroxyproline (Hyp), matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in myocardium or serum were determined. Real-time RT-PCR was performed to detect the mRNA expressions of endothelin 1 (ET-1), transforming growth factor beta1 (TGF-beta1). RESULTS: Angoroside C significantly reduced the BP, LVWI and HWI, decreased the content of Ang II, Hyp, diminished cross sectional area of cardiomyocytes and ameliorated collagen deposition. Additionally, it markedly reduced collagen I and III expressions and regulated matrix metalloproteinase-2, 9 and inhibitors of metalloproteinase expressions. Angoroside C also down regulated the gene expressions of ET-1 and TGF-beta1mRNA in myocardium. CONCLUSION: Angoroside C has beneficial effects against ventricular remodeling. The mechanism is likely to be related to decreasing the level of Ang II, attenuating the mRNA expressions of ET 1 and TGF-beta1. PMID- 26141757 TI - The variable chemotherapeutic response of Malabaricone-A in leukemic and solid tumor cell lines depends on the degree of redox imbalance. AB - PURPOSE: The 'two-faced' character of reactive oxygen species (ROS) plays an important role in cancer biology by acting as secondary messengers in intracellular signaling cascades, enhancing cell proliferation and survival, thereby sustaining the oncogenic phenotype. Conversely, enhanced generation of ROS can trigger an oxidative assault leading to a redox imbalance translating into an apoptotic cell death. Intrinsically, cancer cells have higher basal levels of ROS which if supplemented by additional oxidative insult by pro oxidants can be cytotoxic, an example being Malabaricone-A (MAL-A). MAL-A is a plant derived diarylnonanoid, purified from fruit rind of the plant Myristica malabarica whose anti-cancer activity has been demonstrated in leukemic cell lines, the modality of cell death being apoptosis. This study aimed to compare the degree of effectiveness of MAL-A in leukemic vs. solid tumor cell lines. METHODS: The cytotoxicity of MAL-A was evaluated by the MTS-PMS cell viability assay in leukemic cell lines (MOLT3, K562 and HL-60) and compared with solid tumor cell lines (MCF7, A549 and HepG2); further studies then proceeded with MOLT3 vs. MCF7 and A549. The contribution of redox imbalance in MAL-A induced cytotoxicity was confirmed by pre-incubating cells with an antioxidant, N-acetyl L-cysteine (NAC) or a thiol depletor, buthionine sulfoximine (BSO). MAL-A induced redox imbalance was quantitated by flow cytometry, by measuring the generation of ROS and levels of non protein thiols using dichlorofluorescein diacetate (CM H2DCFDA) and 5-chloromethylfluorescein diacetate (CMFDA) respectively. The activities of glutathione peroxidase (GPx), superoxide dismutase, catalase (CAT), NAD(P)H dehydrogenase (quinone 1) NQO1 and glutathione-S-transferase GST were measured spectrophotometrically. The mitochondrial involvement of MAL-A induced cell death was measured by evaluation of cardiolipin peroxidation using 10-N nonyl acridine orange (NAO), transition pore activity with calcein-AM, while the mitochondrial transmembrane electrochemical gradient (?psi(m)) was measured by JC 1, fluorescence being acquired in a flow cytometer. The apoptotic mode of cell death was evaluated by double staining with annexin V-FITC and propidium iodide (PI), cell cycle analysis by flow cytometry and caspase-3 activity spectrophotometrically. The expression of Nrf2 and HO-1 was examined by western blotting. RESULTS: MAL-A demonstrated a higher degree of cytotoxicity in three leukemic cell lines whose IC50 ranged from 12.70 +/- 0.10 to 18.10 +/- 0.95 ug/ml, whereas in three solid tumor cell lines, the IC50 ranged from 28.10 +/- 0.58 to 55.26 +/- 5.90 ug/ml. This higher degree of cytotoxicity in MOLT3, a leukemic cell line was due to a higher induction of redox imbalance, evident by both an increased generation of ROS and concomitant depletion of thiols. This was confirmed by pre-incubation with NAC and BSO, wherein NAC decreased MAL-A induced cytotoxicity by 2.04 fold while BSO enhanced MAL-A cytotoxicity and decreased the IC50 by 5.60 fold. However, in solid tumor cell lines (MCF7 and A549), NAC minimally decreased MAL-A induced cytotoxicity, and BSO increased the IC50 by 1.96 and 2.39 fold respectively. Furthermore, the generation of ROS by MAL-A increased maximally in MOLT3 as the fluorescence increased from 44.28 +/- 7.85 to 273.99 +/- 32.78, and to a lesser degree in solid tumor cell lines, MCF7 (44.28 +/- 14.89 to 207.97 +/- 70.64) and A549 (37.87 +/- 3.24 to 147.12 +/- 38.53). In all three cell lines there was a concomitant depletion of thiols as in MOLT3, the GMFC decreased from 340.65 +/- 60.39 to 62.67 +/- 11.32, in MCF7 (277.82 +/- 50.32 to 100.39 +/- 31.93) and in A549 (274.05 +/- 59.13 to 83.15 +/- 21.43). In MOLT3 as compared to MCF7 and A549, decrease in the activities of GPx, CAT, NQO1 and GST was substantially greater. In all cell lines, the MAL-A induced redox imbalance translated into triggering of initial mitochondrial apoptotic events. Here again, MAL-A induced a higher degree of cardiolipin peroxidation in MOLT3 (67.01%) than MCF7 and A549 (29.15% and 44.30%), as also down regulated the mitochondrial transition pore activity from baseline to a higher extent, GMFC being 48.05 +/- 2.37 to 10.70 +/- 3.97 (MOLT3), 43.55 +/- 3.36 to 15.36 +/- 0.60 (MCF7) and 39.58 +/- 0.4 to 12.65 +/- 1.56 (A549). Perturbation of mitochondrial membrane potential evident by a decrease in the ratio of red/green (J aggregates/monomers) was 134 fold (14.73/0.11) in MOLT3, 45 fold in MCF7 (20.72/0.46) and 34 fold in A549 (22.01/0.64). The extent of apoptosis using a similar concentration of MAL-A was maximal in MOLT3, wherein a 105 fold increase in annexin V binding was evident (0.83 +/- 0.51 to 87.08 +/- 9.85%) whereas it increased by 43.11 fold in MCF7 (0.69 +/- 0.30 to 29.75 +/- 11.79%) and 47.52 fold in A549 (0.61 +/- 0.31 to 28.99 +/- 17.21%). MAL-A induced apoptosis was also associated with a higher degree of caspase-3 activity in MOLT3 vs. MCF7 or A549 which translated into halting of cell cycle progression, evident by an increment in the sub-G0/G1 population [19.26 fold in MOLT3 (0.95 +/- 0.45 vs. 18.30 +/- 1.90%), 11.01 fold in MCF7 (0.97 +/- 0.37 vs. 10.68 +/- 0.69%) and 8.58 fold in A549 (1.06 +/- 0.45 vs. 9.10 +/- 1.05%)]. MAL-A effectively inhibited Nrf2 and HO-1, more prominently in MOLT3. Furthermore, the decreased expression of Nrf2 in MOLT3 correlated with the decreased activities of NQO1 and GST, suggesting that targeting of the Nrf2 anti-oxidant pathway could be considered. CONCLUSION: Taken together, MAL-A a pro-oxidant compound is likely to be more effective in leukemias, meriting further pharmacological consideration. PMID- 26141758 TI - Anti-hepatitis B virus activities of friedelolactones from Viola diffusa Ging. AB - BACKGROUND: Hepatitis B virus (HBV) infection is the major factor of causing hepatitis B, cirrhosis and liver cancer. Interferon and nucleoside drugs, the main drugs to treat HBV infection, have disadvantages of scavenge difficulty and drug resistance respectively. Viola diffusa Ging is used as a traditional Chinese herbal medicine for the treatment of hepatitis. PURPOSE: The aim of the study is to investigate the chemical constituents of Viola diffusa Ging and their anti-HBV activity. METHODS: Chemical constituents were extracted and purified by ethanol reflux extraction and chromatographic separation technology including D-101 Macroporous resin, silica gel, Sephadex LH-20 and preparative thin-layer chromatography. Their structures were elucidated on the basis of extensive NMR and MS data. Cytotoxicity and inhibiting effects on HBsAg and HBeAg secretion of HepG2.2.15 of all compounds except 10 were studied by MTT method and ELISA method. RESULTS: Three friedelolactones with naturally occurring seco-ring-A friedelane triterpenoids, 2beta-hydroxy-3, 4-seco-friedelolactone-27-oic acid (1), 2beta, 28beta-dihydroxy-3,4-seco-friedelolactone-27-oic acid (2) and 2beta, 30beta-dihydroxy-3,4-seco-friedelolactone-27-lactone (3), and a stigmastane, stigmast-25-ene-3beta,5alpha,6beta-triol (11) together with nine known compounds were isolated from the whole plant of Viola diffusa G. (Violaceae). Compounds 1 3, 9, 11, 12 exhibited significant activities of blocking both HBsAg and HBeAg secretion, and compound 4, 6, 7, 8 selectively inhibited HBeAg secretion while compound 13 selectively inhibited HBsAg secretion. IC50 values of compounds 1 and 2, 26.2 MUM and 33.7 MUM for HBsAg, 8.0 MUM and 15.2 MUM for HBeAg, was significantly lower than that of positive control lamivudine. CONCLUSION: Compounds 1-3, 11 are new compounds never reported before and the promising results demonstrate the potential of compound 1-3, 9, 11, 12 for the treatment of HBV infection. PMID- 26141759 TI - Antitumor activity of tatariside F isolated from roots of Fagopyrum tataricum (L.) Gaertn against H22 hepatocellular carcinoma via up-regulation of p53. AB - BACKGROUND: Fagopyrum tataricum (L.) Gaertn is a famous drinking food and herbal medicine in China, and have been commonly used for treating various diseases. PURPOSE: This study was designed to investigate the antitumor effect of tatariside F (TF) isolated from the roots of F. tataricum against H22 hepatocellular carcinoma (HCC) in vitro and in vivo and explore the possible mechanisms. METHODS: In our present study, the anti-proliferative effect of TF against H22 cells was evaluated by MTT method. Furthermore, a mice xenograft model was established to investigate the antitumor effect of TF on HCC in vivo, and the possible mechanisms were determined by western blot and fluorescence polarization binding assay. In addition, the protective effect of TF on liver was also investigated by examining the histopathological changes and determining the liver biochemical parameters. RESULTS: Our results demonstrated that TF possessed notable antitumor effect against HCC both in vivo and in vitro, and the possible mechanism might be related to up-regulation of the protein expressions of Bax and p53, and down-regulation of Bcl-2. What's more, TF also exhibited protective effects against CTX (cyclophosphamide)-induced liver damages when co administrated with CTX. CONCLUSION: Our study suggested that TF possess notable antitumor effects against HCC and might play a favorable role in drug combination therapy against tumors with protective effect on liver. PMID- 26141760 TI - Cytotoxicity of two naturally occurring flavonoids (dorsmanin F and poinsettifolin B) towards multi-factorial drug-resistant cancer cells. AB - INTRODUCTION: The expression of diverse resistance mechanisms in cancer cells is one of the major barriers to successful cancer chemotherapy. METHODS: In the present study, we assessed the cytotoxicity of two naturally occurring flavonoids dorsmanin F (1, a flavanone) and poinsettifolin B (2, a chalcone) against 9 drug sensitive and multidrug-resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analysed via flow cytometry. RESULTS: Compounds 1 and 2 displayed cytotoxic effects with IC50 values below 34 uM in all the 9 tested cancer cell lines. The IC50 values for flavanone 1 and chalcone 2 ranged from 5.34 uM and 1.94 uM (towards leukaemia CCRF-CEM cells) to 33.30 uM and 28.92 uM (towards MDA MB-231-BCRP cells), respectively, and from 0.20 uM (against CCRF-CEM cells) to 195.12 uM (against CEM/ADR5000 cells) for doxorubicin. The compounds induced apoptosis in CCRF-CEM leukaemia cells, mediated by MMP disruption and increased ROS production. CONCLUSIONS: Dorsmain F and poinsettifolin B are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers. PMID- 26141761 TI - Astaxanthin induces angiogenesis through Wnt/beta-catenin signaling pathway. AB - OBJECTIVE: In the present study, we sought to elucidate whether astaxanthin contributes to induce angiogenesis and its mechanisms. MATERIALS AND METHODS: To this end, we examined the role of astaxanthin on human brain microvascular endothelial cell line (HBMEC) and rat aortic smooth muscle cell (RASMC) proliferation, invasion and tube formation in vitro. For study of mechanism, the Wnt/beta-catenin signaling pathway inhibitor IWR-1-endo was used. HMBECs and RASMCs proliferation were tested by cell counting. Scratch adhesion test was used to assess the ability of invasion. A matrigel tube formation assay was performed to test capillary tube formation ability. The Wnt/beta-catenin pathway activation in HMBECs and RASMCs were tested by Western blot. RESULTS: Our data suggested that astaxanthin induces angiogenesis by increasing proliferation, invasion and tube formation in vitro. Wnt and beta-catenin expression were increased by astaxanthin and counteracted by IWR-1-endo in HMBECs and RASMCs. Tube formation was increased by astaxanthin and counteracted by IWR-1-endo. CONCLUSIONS: It may be suggested that astaxanthin induces angiogenesis in vitro via a programmed Wnt/beta-catenin signaling pathway. PMID- 26141762 TI - Widespread pain reliever profile of a flower extract of Tanacetum parthenium. AB - BACKGROUND: Tanacetum parthenium L., commonly called Feverfew, is known for anti inflammatory and anti-migraine properties. PURPOSE: Aimed to individuate new therapeutical strategies to control acute and persistent pain induced by different origins we tested two hydroalcoholic extracts obtained from Feverfew flowers and leaves, respectively. STUDY DESIGN: Extracts were characterized according to the European Pharmacopoeia monograph. Both the extracts were tested after acute per os administration in the dose range 30-1000 mg kg(-1). The anti nociceptive properties were evaluated by the Writhing test in mice. RESULTS: The number of abdominal contractions was dose dependently reduced by the flower extract. It reduced mechanical hypersensitivity (Paw pressure test) related to the acute inflammatory phase induced by carrageenan similarly to diclofenac and ibuprofen. In the osteoarthritis model induced by intra articular injection of monoiodoacetate (MIA) the flower extract significantly increased the pain threshold peaking 30 min after treatment. Moreover, it was effective in the chronic constriction injury model of neuropathic pain showing activity similar to the anti-epileptic drug gabapentin. The flower extract activity was confirmed in rat models of chemotherapy-induced neuropathic pain. The mechanical hypersensitivity induced by repeated treatments with the anticancer drug oxaliplatin and with the antiviral dideoxycytidine was significantly reduced after a single injection of Feverfew flower extract. The leaf extract showed lesser efficacy and potency and it was devoid of any effect in carrageenan-, MIA- and chemotherapy-induced pain. CONCLUSION: The present Feverfew flower extract behaves as a potent pain reliever in acute, inflammatory, articular and neuropathic pain. It appears as a natural strategy potentially suitable for the treatment of different kinds of pain. PMID- 26141763 TI - Antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin isolated from Angelica keiskei roots through the inhibited activation and differentiation of M2 macrophages. AB - BACKGROUND: Tumor growth and metastasis have been closely associated with the M2 macrophage-induced activation of tumor-associated macrophages (TAMs). PURPOSE: The antitumor and antimetastatic actions of xanthangelol and 4-hydroxyderricin on the role of M2 macrophages in the TAMs of highly metastatic osteosarcoma LM8 bearing mice have not yet been fully elucidated. In order to clarify the mechanisms underlying the antitumor and antimetastatic actions of the above chalcones, we performed in vivo and in vitro studies. STUDY DESIGN: The antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin were examined in vivo and the effects on M2 macrophage differentiation and activation were examined in vitro. METHODS: We examined the antitumor and antimetastatic effects of xanthoangelol and 4-hydroxyderricin on highly metastatic osteosarcoma LM8 bearing mice (in vivo). Further, we examined their effects on the differentiation of interleukin (IL)-4 plus IL-13-induced M2 macrophages and activation of IL-4 plus IL13-induced M2 macrophages (in vitro). We also investigated the expression and phosphorylation of signal transducer and activator of transcript 3 (Stat 3) in the differentiation process of M2-polarized macrophages (in vitro). RESULTS: Xanthoangelol or 4-hydroxyderricin (25 or 50 mg/kg, twice daily) inhibited tumor growth, metastasis to the lung and liver, and TAM expression in tumors. In addition, xanthoangelol (10, 25 or 50 MUM) and 4-hydroxyderricin (5, 10, 25 or 50 MUM) inhibited the production of IL-10 and monocyte chemoattractant protein (MCP) 1 in M2-polarized macrophages. This result indicated that xanthoangelol and 4 hydroxyderricin inhibited the activation of M2 macrophages. Furthermore, xanthoangelol (5-50 MUM) inhibited the phosphorylation of Stat 3 without affecting the expression of the Stat 3 protein in the differentiation process of M2 macrophages, which indicated that these chalcones inhibited the differentiation of M2 macrophages. CONCLUSION: These findings suggested that the antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderrcin might be attributed to the regulated activated TAMs through the inhibition of activation and differentiation of M2 macrophages in the tumor microenvironment. PMID- 26141764 TI - Glycyrrhizin, silymarin, and ursodeoxycholic acid regulate a common hepatoprotective pathway in HepG2 cells. AB - BACKGROUND: Glycyrrhizin, silymarin, and ursodeoxycholic acid are widely used hepatoprotectants for the treatment of liver disorders, such as hepatitis C virus infection, primary biliary cirrhosis, and hepatocellular carcinoma. PURPOSE: The gene expression profiles of HepG2 cells responsive to glycyrrhizin, silymarin, and ursodeoxycholic acid were analyzed in this study. METHODS: HepG2 cells were treated with 25 uM hepatoprotectants for 24 h. Gene expression profiles of hepatoprotectants-treated cells were analyzed by oligonucleotide microarray in triplicates. Nuclear factor-kappaB (NF-kappaB) activities were assessed by luciferase assay. RESULTS: Among a total of 30,968 genes, 252 genes were commonly regulated by glycyrrhizin, silymarin, and ursodeoxycholic acid. These compounds affected the expression of genes relevant various biological pathways, such as neurotransmission, and glucose and lipid metabolism. Genes involved in hepatocarcinogenesis, apoptosis, and anti-oxidative pathways were differentially regulated by all compounds. Moreover, interaction networks showed that NF-kappaB might play a central role in the regulation of gene expression. Further analysis revealed that these hepatoprotectants inhibited NF-kappaB activities in a dose dependent manner. CONCLUSION: Our data suggested that glycyrrhizin, silymarin, and ursodeoxycholic acid regulated the expression of genes relevant to apoptosis and oxidative stress in HepG2 cells. Moreover, the regulation by these hepatoprotectants might be relevant to the suppression of NF-kappaB activities. PMID- 26141765 TI - Quercetin-POM (pivaloxymethyl) conjugates: Modulatory activity for P-glycoprotein based multidrug resistance. AB - BACKGROUND: We previously demonstrated that the bioactivity of quercetin could be improved through conjugation with a hydrolysable pivaloxymethyl (POM) group. PURPOSE: Present study aimed to evaluate MDR (multidrug resistance)-modulatory activity of the quercetin-POM conjugates. STUDY DESIGN/METHODS: MDR-modulatory activity was determined by measuring cytotoxicity of various anticancer agents to MDR MES-SA/Dx5 cell lines upon combination with the quercetin-POM conjugates. RESULTS: The quercetin-7-O-POM conjugate (7-O-POM-Q) was significantly more potent than quercetin in reversing MDR, which recovered the cytotoxicity of various anticancer agents with EC50 values of 1.1-1.3 uM. A series of mechanistic studies revealed that 7-O-POM-Q competes with verapamil in binding to the same drug-binding site of the major MDR target, Pgp (P-glycoprotein), and inhibits Pgp mediated drug efflux with a similar potency as verapamil. The physicochemical properties of 7-O-POM-Q were then evaluated, which confirmed that 7-O-POM-Q has remarkably enhanced cellular uptake and intracellular localization compared with quercetin. Additionally, it is noteworthy that 7-O-POM-Q undergoes slow hydrolysis to quercetin over a prolonged period of time. CONCLUSION: The quercetin-POM conjugate showed significantly improved MDR-reversing activity compared with quercetin, which could be attributed to its capacity to maintain high intracellular concentrations. PMID- 26141766 TI - Analyzing the performance of the planning system by use of AAPM TG 119 test cases. AB - Our objective in this study was to create AAPM TG 119 test plans for intensity modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in the Monaco planning system. The results were compared with the published studies, and the performance of the Monaco planning system was analyzed. AAPM TG 119 proposed a set of test cases called multi-target, mock prostate, mock head and neck and C-shape to ascertain the overall accuracy of IMRT planning, measurement, and analysis. We used these test cases to investigate the performance of the Monaco planning system for the complex plans. For these test cases, we created IMRT plans with static multi-leaf collimator (MLC) and dynamic MLC by using 7-9 static beams as explained in TG-119. VMAT plans were also created with a 320 degrees arc length and a single or double arc. The planning objectives and dose were set as described in TG 119. The dose prescriptions for multi-target, mock prostate, mock head and neck, and C-shape were taken as 50, 75.6, 50 and 50 Gy, respectively. All plans were compared with the results of TG 119 and the study done by Mynampati et al. Point dose and fluence measurements were done with a CC13 chamber and ArcCHECK phantom, respectively. Gamma analysis was done for the calculated and measured dose. Using the Monaco planning system, we achieved the goals mentioned in AAPM TG-119, and the plans were comparable to those of other studies. A comparison of point dose and fluence showed good results. From these results, we conclude that the performance of the Monaco planning system is good for complex plans. PMID- 26141767 TI - Automatic ROI construction for analyzing time-signal intensity curve in dynamic contrast-enhanced MR imaging of the breast. AB - Our purpose in this study was to construct a 3-dimensional (3D) region of interest (ROI) for analyzing the time-signal intensity curve (TIC) semi automatically in dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging of the breast. DCE-MR breast imaging datasets were acquired by a 3.0-Tesla MR system with the use of a 3D fast gradient echo sequence. The essential idea in the new method was to analyze each pixel and to construct an ROI made up of pixels with similar TICs. First, an analyst selected a starting point in the contrast media enhanced tumor. Second, we calculated Pearson's correlation coefficients (CCs) between the TIC in the starting coordinate selected by the analyst and the TIC in the other coordinates. Third, ROI pixels were selected if their CC threshold satisfied a level of coefficient variation of the ROI determined by prior research performed in our institution. We made a retrospective review of patients who underwent breast DCE-MR examination for pre-operative diagnosis. To confirm the feasibility of the resulting 3D-ROI from TIC analysis, we compared Fischer's score obtained from 3D-ROI by applying a new method to a score obtained from a manually selected 2-dimensional (2D) ROI which was used during routine clinical examination. The Fischer's scores obtained from both the automatically selected 3D-ROI and the manually selected 2D-ROI showed almost equivalent results. Thus, we considered that the new method was comparable to the conventional method. Furthermore, the new method has the potential to be used for evaluation of the extent of tumors. PMID- 26141768 TI - Enterococcus faecalis Inhibits Osteoblast Differentiation and Induces Chemokine Expression. AB - INTRODUCTION: Enterococcus faecalis is commonly found in root canals of patients with refractory apical periodontitis, often accompanying inflammation and malfunctioning bone regeneration. In this study, we investigated the effect of E. faecalis on osteoblast differentiation and the ability to induce chemokine expression to recruit inflammatory cells. METHODS: Osteoblast precursors from mouse calvaria were differentiated into osteoblasts with ascorbic acid and beta glycerophosphate in the absence or presence of heat-killed E. faecalis (HKEF). Alizarin red S staining was performed to determine the degree of mineralization. Reporter gene and reverse-transcription polymerase chain reaction assays were performed to examine the activity of the Runx2 transcription factor and the expression of osteogenic marker genes, respectively. Secretion of the chemokines keratinocyte-derived chemokine and monocyte chemotactic protein-1 was measured by the enzyme-linked immunosorbent assay, and their functions were analyzed by measuring the migration of peripheral blood mononuclear cells using a transwell system. RESULTS: HKEF inhibited osteoblast mineralization and Runx2 transcriptional activity, which are typical features of osteoblast differentiation. HKEF also decreased the expression of Runx2, osterix, beta catenin, osteocalcin, and type I collagen. Interestingly, however, the expression of keratinocyte-derived chemokine and monocyte chemotactic protein-1 was increased by HKEF, and the culture supernatant of HKEF-stimulated osteoblasts increased the transmigration of peripheral blood mononuclear cells. CONCLUSIONS: HKEF inhibits osteoblast differentiation and induces chemokine expression, which might be involved in refractory apical periodontitis and bone loss. PMID- 26141769 TI - Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53 MDM2 interaction with a distinct binding mode. AB - Blocking the interaction between the p53 tumor suppressor and its regulatory protein MDM2 is a promising therapeutic concept under current investigation in oncology drug research. We report here the discovery of the first representatives of a new class of small molecule inhibitors of this protein-protein interaction: the dihydroisoquinolinones. Starting from an initial hit identified by virtual screening, a derivatization program has resulted in compound 11, a low nanomolar inhibitor of the p53-MDM2 interaction showing significant cellular activity. Initially based on a binding mode hypothesis, this effort was then guided by a X ray co-crystal structure of MDM2 in complex with one of the synthesized analogs. The X-ray structure revealed an unprecedented binding mode for p53-MDM2 inhibitors. PMID- 26141770 TI - Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene 3-ones via ring-opening/elimination and 'click' strategy. AB - To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan 1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluations against HepG2, Caski and HeLa cell lines, three steroidal triazoles 5b, 5f and 5m in this library were found to possess potent anti-proliferative effects against Caski cells with the half-inhibitory concentrations (IC50) of 9.4 11.8 MUM. The high-efficient and straightforward process was attractive feature for facile preparation of anti-tumor steroidal triazoles. PMID- 26141771 TI - Structure activity relationship of pyridoxazinone substituted RHS analogs of oxabicyclooctane-linked 1,5-naphthyridinyl novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-6). AB - Oxabicyclooctane linked 1,5-naphthyridinyl-pyridoxazinones are novel broad spectrum bacterial topoisomerase inhibitors (NBTIs) targeting bacterial DNA gyrase and topoisomerase IV at a site different than quinolones. Due to lack of cross-resistance to known antibiotics they present excellent opportunity to combat drug-resistant bacteria. A structure activity relationship of the pyridoxazinone moiety is described in this Letter. Chemical synthesis and activities of NBTIs with substitutions at C-3, C-4 and C-7 of the pyridoxazinone moiety with halogens, alkyl groups and methoxy group has been described. In addition, substitutions of the linker NH proton and its transformation into amide analogs of AM-8085 and AM-8191 have been reported. Fluoro, chloro, and methyl groups at C-3 of the pyridoxazinone moiety retained the potency and spectrum. In addition, a C-3 fluoro analog showed 4-fold better oral efficacy (ED50 3.9 mg/kg) as compared to the parent AM-8085 in a murine bacteremia model of infection of Staphylococcus aureus. Even modest polarity (e.g., methoxy) is not tolerated at C 3 of the pyridoxazinone unit. The basicity and NH group of the linker is important for the activity when CH2 is at the linker position-8. However, amides (with linker position-8 ketone) with a position-7 NH or N-methyl group retained potency and spectrum suggesting that neither basicity nor hydrogen-donor properties of the linker amide NH is essential for the activity. This would suggest likely an altered binding mode of the linker position-7,8 amide containing compounds. The amides showed highly improved hERG (functional IC50 >30 MUM) profile. PMID- 26141772 TI - 3-Hydroxy-4-pyridinone derivatives designed for fluorescence studies to determine interaction with amyloid protein as well as cell permeability. AB - Finding a cure for Alzheimer's disease is an urgent goal. Multifunctional metal binders are used to elucidate its pathological features and investigated as potential therapeutics. The use of physicochemical and TD-DFT calculations constituted successful strategy in the design of 1-(4-(benzo[d]oxazol-2 yl)phenyl)-3-hydroxy-2-methylpyridin-4(1H)-one (HL21) and 1-(4-(benzo[d]thiazol-2 yl)phenyl)-3-hydroxy-2-methylpyridin-4(1H)-one (HL22). We report the synthesis and full characterization of these compounds, including X-ray crystallography. Using fluorescent signal as the readout, it was determined that HL22 interacts with amyloid-beta protein fibrils, and permeates into bEnd.3 cells used as a mimic of the blood-brain barrier. This provides the first example of direct investigation of our hydroxypyridinone compounds within a biological setting. PMID- 26141773 TI - Systemic Semilunar Valve Replacement in Pediatric Patients Using a Porcine, Full Root Bioprosthesis. AB - BACKGROUND: Management of systemic semilunar valve disease in growing, young patients is challenging. When replacement is necessary, use of a pulmonary autograft is sometimes not possible for anatomic, pathologic, or technical reasons or due to parental or patient preference. We employed a stentless, porcine, full-root bioprosthesis in this setting and report our outcomes. METHODS: Over 9 years (2005 to 2013), 24 patients of mean age 13.1 years (range, 3 months to 20.3 years) underwent operation for mixed stenosis and insufficiency in 16 of 24 (67%), pure insufficiency in 7 of 24 (29%), and pure stenosis in 1 of 24 (4%). Twenty patients had previous interventions of repair or replacement, valvuloplasty, or multiple operations. Survival, follow-up echocardiographic findings, and outcomes were documented. All patients were maintained on daily aspirin. RESULTS: There were no hospital deaths and no early or late deaths over a mean follow-up for 23 patients of 46.1 months (range, 14 months to 9.2 years). One patient moved abroad and was lost to follow-up. Echocardiographic follow-up (mean 34.0 months) demonstrated that no patient developed more than mild insufficiency or moderate stenosis. In total, 20 of 24 (83%) showed no insufficiency and 11 of 24 patients (46%) showed no stenosis. Near or complete normalization of left ventricular mass and dimension was demonstrated. There were no explants and no thromboembolic or bleeding events. CONCLUSIONS: When use of a pulmonary autograft is not an option, the porcine full-root bioprosthesis appears favorable for systemic semilunar valve replacement in the pediatric and young adult population. Of note, when prosthetic degeneration does occur, stenosis predominates rather than insufficiency. Longer term studies are warranted. PMID- 26141774 TI - Assessment of Proliferation and Cytotoxicity in a Biomimetic Three-Dimensional Model of Lung Cancer. AB - BACKGROUND: Decellularized whole-organ scaffolds show great potential in cancer research. They have been used in the biomimetic three-dimensional (3D) culture of non-small cell lung cancer cells, allowing the study of unique aspects of lung cancer biology. However, there are no reproducible assays capable of directly monitoring processes involved in cancer progression within such scaffolds. METHODS: The human adenocarcinoma cell lines H358, PC9, and SW1573 were subjected to biomimetic 3D culture within decellularized lung scaffolds. A resazurin-based reagent was perfused through the scaffold to determine cell viability over the culture period and in response to treatment with cisplatin or erlotinib. RESULTS: The resazurin reduction perfusion assay detected a progressive increase in the reduction of resazurin over time for all cell lines cultured within decellularized lung scaffolds, translating into incremental cell populations. Also, it detected a positive cytotoxic effect in H358- and PC9-seeded scaffolds after treatment with cisplatin, and in PC9-seeded scaffolds after treatment with erlotinib. Moreover, it identified relative resistance to erlotinib in H358- and SW1573-seeded scaffolds. Results from this assay correlated with histopathology, expression of caspase 3, and activity of epidermal growth factor receptor signaling. CONCLUSIONS: The methods described here for the monitoring of lung cancer cell viability under biomimetic 3D culture conditions within decellularized lung scaffolds permit the study of cancer cell proliferation, the evaluation of responses to therapeutic interventions, and the determination of relative chemo-sensitivities. PMID- 26141775 TI - Continued Utility of Single-Lung Transplantation in Select Populations: Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: The use of single lung transplantation (SLTx) for chronic obstructive pulmonary disease is often viewed as inferior therapy compared with bilateral lung transplantation (BLTx). We hypothesized from our experience that subpopulations of recipients with emphysema exist in which SLTx represents therapy that is equivalent to BLTx, therefore allowing more patients access to transplantation. METHODS: Consecutive patients undergoing LTx for emphysema between 1992 and 2012 at a single institution were identified and analyzed retrospectively. A similar cohort from the United Network of Organ Sharing (UNOS) national database was identified for comparison. Five-year survival in patients receiving SLTx and those receiving BLTx were compared using Kaplan-Meier survival curves and log-rank tests. RESULTS: Two hundred thirty-six patients meeting criteria were identified from our institution. Two hundred six underwent SLTx, and 30 underwent BLTx. Five-year survival for single-center SLTx (53.2% +/- 3.6%) and BLTx (56.7% +/- 10.2%) was not significantly different (p = 0.753). The national database included 7,256 patients meeting selection criteria, with 4,408 undergoing SLTx and 2,848 undergoing BLTx. Five-year survival among the national cohorts was lower for SLTx (46.4% +/- 0.8%) compared with BLTx (55.9% +/- 1.1%) (p < 0.0001). However, 5-year survival for our single-center SLTx experience (53.2% +/- 3.6%) was comparable to the national BLTx cohort (55.9% +/- 1.1%) (p = 0.539). CONCLUSIONS: Five-year survival after SLTx for emphysema was comparable to that for BLTx in cohorts from our institution and from the UNOS national database. Further study should focus on the mechanism behind these improved outcomes. Given the potential for a larger number of life-years saved, SLTx should continue to be considered a therapeutic option in appropriately selected patients with chronic obstructive pulmonary disease (COPD). PMID- 26141776 TI - The Externally Supported Ross Operation: Early Outcomes and Intermediate Follow Up. AB - BACKGROUND: The externally supported Ross (supported Ross), consisting of a Dacron (DuPont, Wilmington, DE) graft to support the neoaortic root, has been used in adolescent and adult patients to prevent neoaortic dilatation. Outcomes after the supported Ross technique were compared with the Ross procedure using the standard aortic root replacement technique (standard Ross). METHODS: This was a retrospective analysis of 36 adolescent and young adult patients who underwent the Ross procedure between 1992 and 2013. The outcomes of supported Ross procedures in 26 patients were compared with the Ross procedure in 10 patients. End points included survival, neoaortic root dilatation, development of neoaortic regurgitation, and the need for reintervention. RESULTS: The median age at operation was 14 years (range, 11 to 31 years), and indications for the operation were mixed lesions (47%), followed by aortic regurgitation (42%) and stenosis (11%). There were no early deaths. The mean follow-up was 2.2 years (range, 1 to 11 years). At the 1-year (p = 0.01) and 3-year (p < 0.05) follow-up, patients in the supported Ross cohort had a smaller neoaortic root z-score. Neither cohort had a large number of patients with significant neoaortic regurgitation, with 1 patient in the supported cohort compared with 3 patients in the standard cohort. Overall, 4 patients (40%) in the standard Ross cohort had required reintervention, including 3 directed at the neoaortic root. One patient in the supported Ross cohort required early reintervention for revision of the right coronary artery. CONCLUSIONS: At intermediate follow-up, patients who underwent the supported Ross technique were less likely to have neoaortic root dilatation compared with patients who underwent a standard Ross procedure. Further studies are needed to evaluate the long-term durability of this technique, particularly in regards to the development of significant aortic regurgitation, the rate of reintervention, and application to younger and smaller patients. PMID- 26141777 TI - Survival After Lung Retransplantation in the United States in the Current Era (2004 to 2013): Better or Worse? AB - BACKGROUND: To understand the current patient survival after lung retransplantation (LRTx) in the United States, which has historically been worse compared with primary lung transplantation (LPTx). METHODS: The United Network for Organ Sharing (UNOS) registry was retrospectively analyzed to determine survival after adult LRTx performed in 604 (2.48%) of 14,850 patients from 2004 to 2013. After exclusions, 582 LRTx and 13,673 LPTx recipients were selected for analysis. Cox proportional hazards regression models were used to determine the prognosticators of survival after LRTx. Survival after LRTx and LPTx were compared using Kaplan-Meier analysis. RESULTS: The median survival after LRTx was 2.6 years compared with 5.6 years after LPTx. One-year, 3-year, and 5-year survival rates were, respectively, 71.1%, 46.3%, and 34.5% for LRTx, and 84.3%, 66.5%, and 53.3% for LPTx (p < 0.001). On multivariate analysis, patients who had LRTx after a greater than 1-year interval survived longer (relative risk [RR] 0.53; 95% confidence interval [CI] 0.34% to 0.88%; p = 0.008). Lower survival was associated with single-lung transplantations (RR 1.49; 95% CI, 1.06% to 2.07%; p = 0.021), transplantations done between 2009 and 2013 (RR 1.40; CI, 1.01% to 1.94%; p = 0.041), multiple (>1) retransplantations (RR 2.55; 95% CI, 1.14% to 5.72%; p = 0.023), and recipients requiring pre-transplantation ventilator support. The only significant donor variable for poor survival was death due to cerebrovascular accidents (RR 1.98; 95% CI, 1.23% to 3.18%; p = 0.004). CONCLUSIONS: Patient survival after LRTx in the United States has improved compared with historical data but remains lower than LPTx. Careful recipient selection and preoperative optimization based on the factors identified in our study may help utilize resources better and improve survival after LRTx. Bilateral LRTx should be preferentially performed as much as possible. Poor candidates for LRTx include those requiring retransplantations more than once or within 1 year. Prospective multi-institutional studies are necessary to help better understand the actual role of these factors in LRTx. PMID- 26141778 TI - Blood Transfusions After Pediatric Cardiac Operations: A North American Multicenter Prospective Study. AB - BACKGROUND: Red blood cell transfusion is an important supportive measure after pediatric cardiac operations. However, no clear hemoglobin threshold has been established. This study characterized anemia development and red blood cell transfusions in the pediatric intensive care unit (PICU) after cardiac operations. METHODS: A prospective, multicenter, 6-month cohort study on the management of anemia in critically ill pediatric patients was conducted in 30 North American PICUs. This observational study enrolled 977 consecutive children (aged <18 years) who stayed in the PICU for 48 hours or more. We analyzed a subgroup of postcardiac surgical patients from this study. RESULTS: Included were 175 cardiac patients, 56% of whom had cyanotic heart disease. The mean Pediatric Risk of Mortality (PRISM III) score was 6.4 +/- 5.4. Fifty-four percent of children were anemic in the PICU (20% on admission, 34% during PICU stay). Most patients (79%) received at least one red blood cell transfusion in the PICU. Patients who received a transfusion had a significantly longer PICU stay (9.3 +/- 6.3 vs 6.1 +/- 5.4 days, p = 0.01). Pretransfusion hemoglobin was different in acyanotic and cyanotic patients (mean +/- standard deviation: 11.1 +/- 2.2 g/dL and 11.8 +/- 2.1 g/dL, respectively). According to the attending physician, a low hemoglobin level was the primary indication for transfusion in only 17% of cases. CONCLUSIONS: Pediatric cardiac surgical patients are at high risk of receiving red blood cell transfusions. This study, which showed great variability in transfusion practices across North American PICUs, highlights the need for clearer transfusion guidelines in this specific population. PMID- 26141779 TI - beta2-Adrenoreceptor Agonist Inhalation During Ex Vivo Lung Perfusion Attenuates Lung Injury. AB - BACKGROUND: Attenuation of ischemia reperfusion injury (IRI) is important in lung transplantation. Our group previously reported that beta2-adrenoreceptor agonist inhalation during the period before procurement successfully attenuated IRI in donated lungs after cardiac death. We therefore hypothesized that beta2 adrenoreceptor agonist inhalation during ex vivo lung perfusion (EVLP) after procurement might also have a protective effect. METHODS: Cardiac-dead beagles were left at room temperature for 210 minutes, and all lungs were subsequently procured and subjected to EVLP for 240 minutes. The beagles were allocated to 2 groups: the beta2 group (receiving an aerosolized beta2-adrenoreceptor agonist 20 minutes after initiation of EVLP; n = 7) and the control group (receiving an aerosolized control solvent at the same time point; n = 6). Physiologic data, including lung function, were evaluated during EVLP. RESULTS: The beta2 group showed significantly lower peak airway pressure and pulmonary artery pressure than the control group. Dynamic pulmonary compliance was higher, pulmonary vascular resistance (PVR) was lower, and the wet-to-dry lung weight ratio was lower in the beta2 group than in the control group. Cyclic adenosine monophosphate (cAMP) and total adenosine nucleotide (TAN) levels in lung tissue after EVLP were higher in the beta2 group than in the control group. The beta2 group also showed more cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. CONCLUSIONS: After procurement, beta2-adrenoreceptor agonist inhalation during EVLP attenuates lung injury in a canine model of organ donation after cardiac death. PMID- 26141780 TI - Right Minithoracotomy Versus Median Sternotomy for Mitral Valve Surgery: A Propensity Matched Study. AB - BACKGROUND: The efficacy of conventional median sternotomy versus a right minithoracotomy (RT) approach to mitral valve surgery was evaluated in a single high-volume institution. METHODS: A retrospective analysis of a single institution's experience was performed using propensity matching of 1,694 patients who underwent mitral valve surgery during a 15-year period. Patients who had procedures that were not usually performed through an RT approach were excluded. Using 1:1 propensity score matching, we obtained 215 matched patients in each group for outcomes analysis. RESULTS: There was no difference in the median year of operation between the two groups (2002 versus 2001; p = 0.142). The RT approach was not a predictor of postoperative mortality. Predictors of mortality included increasing age, diabetes, smoking, preoperative dialysis, lung disease, advanced congestive heart failure class, and peripheral vascular disease. The RT approach was associated with less new-onset atrial fibrillation (8% versus 16%; p = 0.018), pneumonia (1% versus 5%; p = 0.049), respiratory failure (3% versus 8%; p = 0.036), and acute renal failure (2% versus 7%; p = 0.006), lower chest tube output (350 versus 840 mL; p < 0.001), and fewer red blood transfusions (2 versus 3 units; p = 0.001). CONCLUSIONS: Right minithoracotomy compared with median sternotomy for mitral valve surgery was associated with less postoperative atrial fibrillation, respiratory complications, acute renal failure, chest tube output, and use of packed red blood cells. Given study limitations, the RT approach for mitral valve surgery may have advantages over median sternotomy in selected patients. PMID- 26141781 TI - Effects of two copper compounds on Microcystis aeruginosa cell density, membrane integrity, and microcystin release. AB - Microcystin release following Microcystis aeruginosa cell lysis after copper based algaecide treatment is often cited as a concern leading to restricted use of algaecide in restoration of natural water resources. To examine this concern, bench-scale experiments were conducted to study responses of M. aeruginosa to 8 day copper exposures as copper sulfate and copper-ethanolamine (Cu-EA). M. aeruginosa UTEX 2385 was cultured in BG11 medium to cell density of 10(6)cells/mL with total and extracellular microcystin of 93 and 53MUg/L, respectively. Exposures of copper concentration ranged from 40 to 1000MUgCu/L. Cell membrane integrity was indicated by erythrosine B. In the end of experiment, total microcystin and cell density in untreated control (313MUg/L and 10(7)cells/mL) was 3.3 and 10 times greater than pretreatment value, respectively. Minimum amount of copper required to reduce M. aeruginosa population within 8 days was 160MUgCu/L as copper sulfate and 80MUgCu/L as Cu-EA, where total and extracellular microcystin concentrations (47 and 44MUg/L for copper sulfate; 56 and 44MUg/L for Cu-EA) were degraded with degradation rate coefficient 0.1 day( 1) and were less than pretreatment values. Given a copper concentration at 80ugCu/L as Cu-EA, M. aeruginosa cells were intact and less microcystin were released compared to treatments at 160-1000ugCu/L, where lysed cells and relatively greater microcystin release were observed. Based on the laboratory results, a minimum amount of copper required for reducing M. aeruginosa population could decrease total microcystin concentration and not compromise cells and minimize microcystin release. PMID- 26141782 TI - Tracheal Self-Expandable Metallic Stents: A Comparative Study of Three Different Stents in a Rabbit Model. AB - INTRODUCTION: The objective of this study was to assess tracheal reactivity after the deployment of different self-expandable metal stents (SEMS). MATERIAL AND METHODS: Forty female New Zealand rabbits were divided into four groups. Three groups received three different SEMS: steel (ST), nitinol (NiTi), or nitinol drug eluting stent (DES); the fourth group was the control group (no stent). Stents were deployed percutaneously under fluoroscopic guidance. Animals were assessed by multi-slice, computed tomography (CT) scans, and tracheas were collected for anatomical pathology (AP) study. Data from CT and AP were statistically analyzed and correlated. RESULTS: The DES group had the longest stenosis (20.51+/-14.08mm vs. 5.84+/-12.43 and 6.57+/-6.54mm in NiTi and ST, respectively, day 30; P<.05), and higher granuloma formation on CT (50% of cases). The NiTi group showed the lowest grade of stenosis (2.86+/-6.91% vs. 11.28+/-13.98 and 15.54+/-25.95% in DES and ST, respectively; P<.05). The AP study revealed that the ST group developed intense proliferative reactivity compared to the other groups. In the DES group, a destructive response was observed in 70% of the animals, while the NiTi was the least reactive stent. CT was more effective in detecting wall thickening (positive correlation of 68.9%; P<.001) than granuloma (not significant). CONCLUSIONS: The ST group developed granulomas and significant stenosis. NiTi was the least reactive stent, while DES caused significant lesions that may be related to drug dosage. This type of DES stent is therefore not recommended for the treatment of tracheobronchial stenosis. PMID- 26141783 TI - Comparison of T1rho and T2* Relaxation Mapping in Patients with Different Grades of Disc Degeneration at 3T MR. AB - BACKGROUND: T1rho and T2* relaxation times are capable of providing information about early biochemical changes in intervertebral disk degeneration (IVDD). The purpose of this study was to assess and compare T1rho and T2* mapping in IVDD with reference to Pfirrmann grade. MATERIAL AND METHODS: Lumbar sagittal T2 weighted, T1rho and T2* relaxation MRI were performed at 3.0T in 42 subjects covering discs L1-L2 to L5-S1. All the discs were morphologically assessed according to the Pfirrmann grade. Regions of interest (ROIs) were drawn over the T1rho and T2*mappings, including nucleus pulposus (NP) and annulus fibrosus (AF). Wilcoxon signed rank test, Kruskal-Wallis test, and Spearman rank correlation were performed. RESULTS: The difference in T1rho and T2* values between NP and AF were highly significant (P<0.001). The trends of decreasing T1rho and T2* values of both NP and AF with increasing Pfirrmann grades was significant (P<0.01), particularly between Pfirrmann grade II and III (P<0.001), whereas T2* mapping was additionally able to detect changes in the AF between Pfirrmann grade I and II (P<0.05). Pfirrmann grades were inversely significantly correlated with both T1rho and T2* values in the NP (r=-0.69, P<0.001; r=-0.56, P<0.001) and AF (r= 0.45, P<0.001; r=-0.26, P<0.001). CONCLUSIONS: The process of IVDD can be detected by T1rho and T2* mapping, particularly at early stage, and both methodologies displayed roughly comparable performance. PMID- 26141784 TI - Preoperative chemotherapy for T2 breast cancer is associated with improved surgical outcome. AB - BACKGROUND: The aim of this study is to compare the clinical outcome in T2 breast cancer patients who underwent preoperative chemotherapy (PC) and who did not. The study also tried to define a subgroup of patients, who are more beneficial after PC in terms of lower re-excision rates, better cosmetic results and local recurrence free survival. MATERIALS AND METHODS: 251 consecutive patients treated for nonmetastatic T2 invasive breast cancer were analyzed retrospectively. Of those; 141 underwent primary surgery (PS) followed by chemotherapy, whereas 110 were treated with combination of PC and surgery. RESULTS: The patients who were treated with PC had a significantly higher incidence of negative margins and lower rate of re-excision (5% vs. 16%, p = 0.02). Of all patients attempted breast conserving surgery (BCS), patients in the PC group were more likely to undergo BCS as their definitive operation compared to patients with PS group (BCS rates; PC group: 99% vs. PS group: 92%, p = 0.05). Multifocal disease (OR: 7, 95% Cl, 2.7-18.4, p = 0.0001) and PC (OR = 0.2; 95% CI, 0.06-0.72, p = 0.01) were factors associated with margin positivity in patients treated with BCS. There was no statistically significant difference in 5 year local-recurrence free survival rates between 2 groups. CONCLUSIONS: Our study shows that PC significantly decreases the re-excision in patients undergoing BCS with primary T2 breast tumors. This data suggests that any patient with a tumor greater than 2 cm might be considered for PC to increase BCS success with final negative margins. PMID- 26141785 TI - Derivation of human induced pluripotent stem cells through continued exposure of OCT4-induced plastic human fibroblasts to reprogramming media. AB - The combination of OCT4 expression and short-term exposure to reprogramming media induces a state of transcriptional plasticity in human fibroblasts, capable of responding to changes in the extracellular environment. Here we provide characterization of iPSCs established through continued culture of OCT4-induced plastic human fibroblasts in pluripotent-supportive reprogramming media. Human iPSC(OCT4) are morphologically indistinguishable from conventionally derived iPSCs and express core proteins involved in maintenance of pluripotency. iPSC(OCT4) display bona fide functional pluripotency as measured by in vivo teratoma formation consisting of the three germ layers. PMID- 26141786 TI - Association of Venous Disorders with Leg Symptoms: Results from the Bonn Vein Study 1. AB - OBJECTIVES: The aim was to study the association between venous disorders and leg symptoms in the population based cross sectional Bonn Vein Study 1 (BVS1). METHODS: A total of 1,350 men and 1,722 women aged 18-79 years were enrolled into BVS1. Chronic venous insufficiency (CVI), varicose veins (VVs), and clinical classes (C-classes/CEAP [Clinical, Etiological, Anatomical, and Pathophysiological]) were determined by clinical and duplex investigation. Leg symptoms (heaviness, tightness, swelling, pain after standing or sitting, pain while walking, muscle cramps, itching, and restless legs) were assessed in a standardized interview. For 2,624 subjects (48.7% male) with complete information on venous disorders, relevant characteristics and information on at least one leg symptom, multivariate logistic regression analysis was performed. RESULTS: More women (929/63.0%) reported at least one leg symptom within the last 4 weeks than men (560/48.7%). Prevalence of reported symptoms increased with age (45.4% of the 18-29 year olds, 73.9% of the 70-79 year olds). Leg symptoms were more frequent in obese and underweight subjects. As confirmed by clinical and duplex examination 22.6% had VV and 15.8% had CVI. VV (OR: 1.4; CI: 1.1-1.7) and CVI (OR: 1.8; CI: 1.3-2.3) were significantly associated with reporting at least one leg symptom. In particular, there was a positive association of VV and CVI with itching, feeling of heaviness, tightness, swelling, and pain after standing or sitting. C2-C6 showed a statistically significant association with feeling of heaviness, tightness, swelling, and itching, while for pain on walking and muscle cramps this was shifted towards C classes C3-C6 and C3-C4, respectively. CONCLUSIONS: Venous disorders show significant associations with several leg symptoms. Itching, feeling of heaviness, or tightness seem to be more closely related than other symptoms. The associations between C classes and symptoms seem to be restricted to classes C2 or higher. PMID- 26141787 TI - The Ia-2beta intronic miRNA, miR-153, is a negative regulator of insulin and dopamine secretion through its effect on the Cacna1c gene in mice. AB - AIMS/HYPOTHESIS: miR-153 is an intronic miRNA embedded in the genes that encode IA-2 (also known as PTPRN) and IA-2beta (also known as PTPRN2). Islet antigen (IA)-2 and IA-2beta are major autoantigens in type 1 diabetes and are important transmembrane proteins in dense core and synaptic vesicles. miR-153 and its host genes are co-regulated in pancreas and brain. The present experiments were initiated to decipher the regulatory network between miR-153 and its host gene Ia 2beta (also known as Ptprn2). METHODS: Insulin secretion was determined by ELISA. Identification of miRNA targets was assessed using luciferase assays and by quantitative real-time PCR and western blots in vitro and in vivo. Target protector was also employed to evaluate miRNA target function. RESULTS: Functional studies revealed that miR-153 mimic suppresses both glucose- and potassium-induced insulin secretion (GSIS and PSIS, respectively), whereas miR 153 inhibitor enhances both GSIS and PSIS. A similar effect on dopamine secretion also was observed. Using miRNA target prediction software, we found that miR-153 is predicted to target the 3'UTR region of the calcium channel gene, Cacna1c. Further studies confirmed that Cacna1c mRNA and protein are downregulated by miR 153 mimics and upregulated by miR-153 inhibitors in insulin-secreting freshly isolated mouse islets, in the insulin-secreting mouse cell line MIN6 and in the dopamine-secreting cell line PC12. CONCLUSIONS/INTERPRETATION: miR-153 is a negative regulator of both insulin and dopamine secretion through its effect on Cacna1c expression, which suggests that IA-2beta and miR-153 have opposite functional effects on the secretory pathway. PMID- 26141788 TI - Excessive gestational weight gain prior to glucose screening and the risk of gestational diabetes: a meta-analysis. AB - AIMS/HYPOTHESIS: Excessive gestational weight gain (GWG) may be a risk factor for gestational diabetes mellitus (GDM). We aimed to study the association between excessive GWG (defined according to Institute of Medicine recommendations) prior to GDM screening, and GDM. METHODS: We systematically searched four electronic databases from 1990 until September 2014 for observational studies published in English or German that reported an association between excessive GWG and GDM as the outcome. Random effects meta-analyses were performed to provide a pooled estimate of the OR comparing the risk of GDM in women with and without excessive GWG. RESULTS: A total of eight studies involving 13,748 participants were included. The pooled analysis of unadjusted OR yielded a summary OR of 1.40 (95% CI 1.21, 1.61; p < 0.001) with low between-study heterogeneity (I(2) = 16.7%). A sensitivity analysis based on four studies reporting adjusted effect estimates revealed similar results (OR 1.42; 95% CI 1.20, 1.68; p < 0.001; I(2) = 0%). No evidence was found that the effect of GWG on GDM differs depending on maternal pre-pregnancy BMI category. A funnel plot did not indicate substantial publication bias. CONCLUSIONS/INTERPRETATION: Avoiding excessive weight gain in pregnancy prior to the GDM screening test may be a potential strategy to reduce GDM risk. META-ANALYSIS REGISTRATION: www.crd.york.ac.uk/PROSPERO CRD42014008802. PMID- 26141789 TI - Complexation behavior of Eu(III), Tb(III), Tm(III), and Am(III) with three 1,10 phenanthroline-type ligands: insights from density functional theory. AB - Extraction complexes of Eu(III), Tb(III), Tm(III), and Am(III) with three 1,10 phenanthroline-type ligands have been studied, primarily using density functional theory (DFT). The same accuracies and optimized structural geometries were obtained whether optimization of the [ML2(NO3)](2+) complexes was performed at the B3LYP/6-31G(d)/RECP or the MP2/6-31G(d)/RECP level of theory. Calculations carried out at the B3LYP/6-311G(d, p)/RECP level of theory indicated that solvation does not favor the formation of these complexes. Moreover, the DeltaGg and DeltaGsolv values for the reactions leading to the formation of [LnL2(NO3)](2+) complexes were seen to decrease with increasing atomic number of the lanthanide (from Eu to Tb to Tm). In addition, when a strongly hydrophobic benzo[e][1,2,4]triazine group was created in each ligand, ligand selectivity for actinides/lanthanides in acidic media improved. Even greater ligand selectivity for actinides/lanthanides in acidic media was obtained when a 5,6-diphenyl-1,2,4 triazine group was created in each ligand instead of a benzo[e][1,2,4]triazine group. Vibrational analysis and NMR spectroscopic analysis were also performed on all of the studied ligands and the metal complexes that included them. Further in depth investigations should be undertaken in this field. PMID- 26141790 TI - Arm retraction and escape transition in semi-flexible star polymer under cylindrical confinement. AB - We studied the structure and dynamics of star-shaped polymers by means of coarse grained molecular dynamics simulations and analysis of structural transitions of semi-flexible macromolecules confined in nano-channels. The conformation of star arms in narrow channels is given by the channel width, arm flexibility and number of arms aligned together in the given region along the channel. We focused on the conformation transition, where all arms are initially stretched in one direction of the narrow channel and were interested in the process of how individual arms escape into a free volume region of channel. We found that the escape transition does not proceed from arm ends but progresses by extension of a loop starting from the branch point; the arms escape in individual steps and the extension of arms depends on how many arms align in parallel in the channel. PMID- 26141792 TI - Estimating the dilemma strength for game systems: Comment on "Universal scaling for the dilemma strength in evolutionary games", by Z. Wang et al. PMID- 26141791 TI - Characteristics of residual organochlorine pesticides in soils under different land-use types on a coastal plain of the Yellow River Delta. AB - The residual levels of organochlorine pesticides (OCPs) were examined in soils covering five types of land use along a salinity gradient on the Yellow River Delta. The most prominent OCPs were dichlorodiphenyltrichloroethane (?DDT, arithmetic mean = 5.11 MUg kg(-1)), hexachlorocyclohexane (?HCH, 1.69 MUg kg(-1)) and ?endosulfan (10.4 MUg kg(-1)). The spatial variability of OCPs composition shifted from gamma-HCH and o,p'-DDT dominated pesticides in coastal soils to p,p' DDE dominated pesticides in inland soils. In different land-use types, the percentages of beta-HCH and p,p'-DDE are characterized by more recalcitrant components in decreasing order of vegetable fields, cereal fields, cotton fields, wetlands and tidal flats with increasing soil salinity. However, the less recalcitrant components, gamma-HCH and o,p'-DDT, showed an opposite trend. Endosulfan sulfate predominated in all land-use types. Residual levels of beta HCH were affected by soil organic matter. The correlations between gamma-HCH and clay content and between p,p'-DDE, o,p'-DDT and salinity might associate with the influence of sediment cotransport by the Yellow River and the density of anthropogenic activities in coastal region. Depth distribution of the OCPs in typical soil profiles also implied that local historical usage and sediment transport by the Yellow River both affected the OCPs residual in this region. PMID- 26141793 TI - Specialist and generalist oviposition strategies in butterflies: maternal care or precocious young? AB - Herbivorous insects specialized on a narrow set of plants are believed to be better adapted to their specific hosts. This hypothesis is supported by observations of herbivorous insect species with a broader diet breadth which seemingly pay a cost through decreased oviposition accuracy. Despite many studies investigating female oviposition behavior, there is a lack of knowledge on how larvae cope behaviorally with their mothers' egg-laying strategies. We have examined a unique system of five nymphalid butterfly species with different host plant ranges that all feed on the same host plant. The study of this system allowed us to compare at the species level how oviposition preference is related to neonate larval responses in several disadvantageous situations. We found a general co-adaptation between female and larval abilities, where species with more discriminating females had larvae that were less able to deal with a suboptimal initial feeding site. Conversely, relatively indiscriminate females had more precocious larvae with better abilities to cope with suboptimal sites. Despite similarities between the tested species with similar host ranges, there were also striking differences. Generalist and specialist species can be found side by side in many clades, with each clade having a specific evolutionary history. Such clade-specific, phylogenetically determined preconditions apparently have affected how precisely a broad or narrow diet breadth can be realized. PMID- 26141794 TI - On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions. AB - The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. PMID- 26141795 TI - The hypertensive disorders of pregnancy (29.3). AB - Hypertensive disorders are the most common medical complication of pregnancy. As such, a large part of antenatal care is dedicated to the detection of pre eclampsia, the most dangerous of the hypertensive disorders. The highlights of this chapter include progress in the use of out-of-office blood pressure measurement as an adjunct to office blood pressure measurement, pre-eclampsia defined as proteinuria or relevant end-organ dysfunction, antihypertensive therapy for severe and non-severe hypertension and post-partum follow-up to mitigate the increased cardiovascular risk associated with any of the hypertensive disorders of pregnancy. PMID- 26141796 TI - Evaluation of a new lateral flow test for detection of Streptococcus pneumoniae and Legionella pneumophila urinary antigen. AB - Pneumonia is a major cause of morbidity and mortality worldwide. Early diagnosis of the etiologic agent is important in order to choose the correct antibiotic treatment. In this study we evaluated the first commercial combined test for the agents of pneumococcal pneumonia and Legionnaires' disease based on urinary antigen detection, the ImmuView(r) Streptococcus pneumoniae and Legionella pneumophila Urinary Antigen Test. In this evaluation, the new test had a significantly higher sensitivity than the BinaxNOW(r) lateral flow tests and the Binax(r) EIA test. This identifies the ImmuView(r) S. pneumoniae and L. pneumophila Urinary Antigen Test as a fast and sensitive point of care test for identification of the infectious agent in a major group of patients with pneumonia. PMID- 26141797 TI - Harnessing the crowd to accelerate molecular medicine research. AB - Crowdsourcing presents a novel approach to solving complex problems within molecular medicine. By leveraging the expertise of fellow scientists across the globe, broadcasting to and engaging the public for idea generation, harnessing a scalable workforce for quick data management, and fundraising for research endeavors, crowdsourcing creates novel opportunities for accelerating scientific progress. PMID- 26141798 TI - Clinical application of companion diagnostics. AB - Optimally, any prescription should rely on an in-depth understanding of the disease biology and the mechanism of action of the drug. However, despite the hype about precision medicine in recent years, the prescription of most drugs is still, except for a few anticancer drugs, largely based on 'trial and error' and not on solid pharmacogenomic biomarker data. PMID- 26141800 TI - [Knowledge and experience of 2- to 15-year-old children's parents consulting in pediatric emergency departments for asthma]. AB - INTRODUCTION: This study aimed at assessing parents' knowledge and perception in relation to their child's condition when arriving at the emergency ward following an asthma attack. The overall objective was to determine how parent education could be improved. MATERIALS AND METHODS: This study was conducted over 9 months as a multicenter descriptive and qualitative study based on a self-administered questionnaire for parents of asthmatic children, aged 2-15 years. RESULTS: The questionnaire was delivered to 88 children out of 1472 (6%). Approximately 69% of the children included in the study presented with partially controlled or uncontrolled asthma. Fifty percent of the patients were insufficiently monitored and without therapy. Half of the parents said they had never received any information concerning their child's condition. The majority (86%) did not know the basic cause of the disease, 30% percent were unable to detect the features of clinical exacerbation, and 17% were not using an adequate emergency protocol. The illness experience was relatively easy for two-thirds of the children and the parents' perceptions were in line in 50% of the cases. DISCUSSION: Knowledge of parents and their children suffering from asthma is insufficient for optimal control and disease management. Instructions on detecting the signs of asthma severity as well as the establishment of an individualized emergency protocol and medical follow-up should be of prime concern and could reduce emergency department use. CONCLUSION: Doctors have a key role to play in educating and explaining disease characteristics to patients and their families. Therapeutic education also needs to be intensified. PMID- 26141799 TI - Epigenetics and Lymphoma: Can We Use Epigenetics to Prime or Reset Chemoresistant Lymphoma Programs? AB - Non-Hodgkin lymphoma is a diverse group of lymphocyte-derived neoplasms. Although a heterogeneous group of malignancies, it has become apparent that epigenetic alterations, such as disturbances of DNA methylation and histone modification, are a common occurrence in both B cell and T cell lymphomas, contributing to lymphomagenesis. As a result, the use of epigenetic targeted therapy has been incorporated into various pre-clinical and clinical studies, demonstrating significant efficacy in lymphoma, with vorinostat becoming the first epigenetic therapy to receive FDA approval in any malignancy. The role of epigenetic drugs is evolving, with its potential use in combination therapy as well as a means of overcoming chemotherapy resistance. In this review, we discuss the epigenetic alterations in non-Hodgkin lymphomas as well as provide an overview of current epigenetic drugs and their role in clinical practice, and on-going clinical trials. PMID- 26141801 TI - [Vaccination coverage against hepatitis B in first-grade children, Paris, 2002 2008]. AB - INTRODUCTION: The French controversy over the possible risks of vaccination against hepatitis B seems to have resulted in a slowdown or delay in vaccination of target populations since the mid-1990s. This article reports the results of the analysis of vaccination coverage against hepatitis B of first-grade children in Paris between 2002 and 2008. METHODOLOGY: Retrospective and descriptive study of vaccination status against hepatitis B for children born between 1997 and 2002 and attending first grade in a Paris school between 2002 and 2008, using anonymous data from the prevention service of the city of Paris. RESULTS: The analysis included 108,114 children whose Health Book (carnet de sante) included sociodemographic data and the presence of at least one diphtheria-tetanus-polio vaccination. Among these targeted children, 66,597 (61.6%) had started a vaccination against hepatitis B, 61,190 (56.6%) were considered "vaccinated" (at least three doses), and 47,489 (43.9%) "adequately vaccinated" (at least three doses respecting the prescribed intervals between injections). The sociodemographic factors associated with hepatitis B coverage were as follows: Paris arrondissement where the child attended school, year, and country of birth. CONCLUSION: Nearly 40% of the children in this cohort had not been vaccinated against hepatitis B before beginning first grade. They have now become adolescents aged 12-17 years. Current data indicate that only one-third of them have benefited from the catch-up campaign. This finding reinforces the need for vigilance on the vaccination status of adolescents against hepatitis B. PMID- 26141802 TI - [Arthrogryposis: clinical manifestations and management]. AB - INTRODUCTION: Arthrogryposis is a condition existing at birth, seen in different diseases that have in common the existence of multiple joint stiffness. The clinical presentation is diversified and the functional prognosis depends on the etiology, which makes therapeutic options different from one case to another. The objective of this study was to describe clinical manifestations observed in arthrogrypotic patients and show the different therapeutic methods and functional results. METHODS: This was a retrospective study over a period of 12 years from 2000 to 2012, based on clinical examinations of 23 patients with arthrogryposis. RESULTS: The mean age of the patients was 6.6 years. The four limbs were involved in 19 cases and only the lower limbs in four cases. The etiology was amyoplasia in nine patients, distal arthrogryposis in three, peripheral neuropathy in two, and muscular atrophy in one infantile patient. Foot deformities were observed in 22 cases, with 25 talipes equinovarus deformities (clubfoot), six convex feet, and five valgus feet. The Ponseti method was applied in 12 clubfeet with recurrence in eight cases. The other clubfeet had functional treatment and necessitated surgical release in 11 cases. Deformation of the knee was seen in 15 patients, flessum in 16 knees, restriction of flexion in eight cases, genu recurvatum in three, stiffness in extension in two, and agenesis of the patella in one case. Surgical treatment was carried out in only one case. Other cases of deformity of the knee were treated by rehabilitation with slight improvement. Deformation of the hip was seen in 15 patients, with 16 hips dislocated and four hips in flessum. The dislocation of the hip was treated orthopaedically in two cases and surgically in six cases, with reduction in all cases but persistence of stiffness. Involvement of the shoulders was observed in eight cases, the elbow in seven cases, the wrist in ten cases, and the fingers in 16 cases. The treatment was based on physical therapy and orthotics in all cases, and improvement was better in the wrist and fingers. CONCLUSION: Arthrogryposis has different clinical presentations. Successful treatment is not constant. Multidisciplinary care is necessary and should be early and continued in order to gain the maximum autonomy and facilitate patients' social integration. PMID- 26141803 TI - [Kawasaki disease and cranial nerve involvement: two cases]. AB - CNS involvement, except classical lymphocytic meningitis, is exceptionally rare in Kawasaki disease. Herein, we report on two atypical cases of KD with cranial nerve inflammation. The first case presented supranuclear vertical palsy and the second case Bell palsy. Outcome was promptly favorable with IV immunoglobulins, with no long-term complications. No specific KD biomarkers are available and diagnosis of atypical forms is difficult. KD can mimic a systemic illness and appropriate therapy may be delayed. PMID- 26141804 TI - [Vitamin D supplementation: not too much, not too little!]. AB - Vitamin D deficiency is common in the general population and even more frequent in patients with chronic diseases. The prevention of rickets with native vitamin D supplementation is one of the oldest and most effective prophylactic measures ever reported in medicine, leading to an almost complete eradication of vitamin D deficient rickets in developed countries. We report on two children with vitamin D abnormalities: the first, 10-year-old child developed rickets without any vitamin D supplementation despite different risk factors (autism, ethnicity, nutritional problems, chronic antiepileptic therapies). In contrast, the second, 8-month-old child received double doses of native vitamin D from birth for several months and was referred for acute and symptomatic hypercalcemia. As such, vitamin D supplementation must follow specific rules: neither too much nor too little! We also discuss the emergence of "new" genetic diseases such as mutations in the 24-hydroxylase (CYP24A1) gene inducing neonatal hypercalcemia and nephrocalcinosis: we believe that before prescribing conventional vitamin D supplementation as recommended by the national guidelines, pediatricians should quickly rule out a potential genetic abnormality in phosphate/calcium metabolism (namely a history of lithiasis or hypercalcemia) that would lead to further biological investigations. PMID- 26141805 TI - [Oral formulation of choice for children]. AB - Selecting the most appropriate oral formulation is very challenging when developing medicines for children and in routine practice. Research in pediatric pharmacology has focused on oral drug formulation, determining whether the active pharmaceutical ingredient can be successfully delivered to children. Pediatric expert committees (EMA, EuFPI) recommend that children's medicines be safe, well tolerated, easy to use (palatable and requiring minimal handling), transportable, easily produced, cost effective, commercially viable, with a minimal impact on children's life-style. Oral liquid drug formulations (OLFs: solutions, syrups, suspensions) are historically considered as the most appropriate oral formulation for children, since they are easy to swallow for younger infants and palatable for children. However, OLFs present numerous disadvantages, such as low stability, potentially toxic excipients for children, and low transportability. In the long-term, dose volume and frequency of administration might lead to non compliance. Multiple preparation steps and volume calculations are also among risk factors for medicine errors in children. An alternative to OLFs is the conventional solid oral dosage form (OSF), such as tablets and capsules. These offer the advantages of greater stability, easy dose selection, improved transportability, and ease of storage. They also allow the modification of drug pharmacokinetic parameters, minimizing administration frequency. Finally, OSFs are less costly than OLFs, since they are easier to develop, manufacture, transport, store, and deliver. Controlled study results suggest that the use of OSFs in children would be associated with greater acceptability by children, greater preference on the part of caregivers, and higher drug compliance than OLFs. Recent controlled studies, confirming that OSFs with an acceptable size for children (mini-tablets), should shift the current paradigm of OLFs as the reference for children's oral medicine. We lack evidence on OSF acceptability in children and its influence on drug compliance, particularly with appropriate-size OSFs for children. Further investigation on oral formulation should investigate the utilisation of OSFs in young children. Few OSFs are licensed for children under 6 years of age. PMID- 26141807 TI - Anxiety sensitivity and intolerance of uncertainty as potential risk factors for cyberchondria: A replication and extension examining dimensions of each construct. AB - BACKGROUND: Preliminary findings suggest that anxiety sensitivity (AS) and intolerance of uncertainty (IU) may confer vulnerability for cyberchondria, defined as repeated internet searches for medical information that exacerbates health anxiety. Prior studies are limited because it remains unclear whether specific AS or IU dimensions differentially relate to certain cyberchondria dimensions. METHODS: The present study examined associations among AS, IU, and cyberchondria dimensions using a sample of community adults (N = 578) located in the United States. RESULTS: As predicted, physical AS and inhibitory IU were the only AS or IU dimensions to share unique associations with the distress cyberchondria dimension after controlling for the overlap among the AS dimensions, IU dimensions, and health anxiety. Cognitive AS and social AS unexpectedly evidenced unique associations with cyberchondria dimensions. LIMITATIONS: The results are limited by the cross-sectional study design and use of a community, rather than clinical, sample. CONCLUSIONS: This study provides evidence that specific AS and IU dimensions may confer vulnerability to certain cyberchondria dimensions. Further clarifying associations among AS, IU, and cyberchondria may lead to improvements in our conceptualization and, ultimately, treatment of cyberchondria. PMID- 26141806 TI - Universal health coverage from multiple perspectives: a synthesis of conceptual literature and global debates. AB - BACKGROUND: There is an emerging global consensus on the importance of universal health coverage (UHC), but no unanimity on the conceptual definition and scope of UHC, whether UHC is achievable or not, how to move towards it, common indicators for measuring its progress, and its long-term sustainability. This has resulted in various interpretations of the concept, emanating from different disciplinary perspectives. This paper discusses the various dimensions of UHC emerging from these interpretations and argues for the need to pay attention to the complex interactions across the various components of a health system in the pursuit of UHC as a legal human rights issue. DISCUSSION: The literature presents UHC as a multi-dimensional concept, operationalized in terms of universal population coverage, universal financial protection, and universal access to quality health care, anchored on the basis of health care as an international legal obligation grounded in international human rights laws. As a legal concept, UHC implies the existence of a legal framework that mandates national governments to provide health care to all residents while compelling the international community to support poor nations in implementing this right. As a humanitarian social concept, UHC aims at achieving universal population coverage by enrolling all residents into health-related social security systems and securing equitable entitlements to the benefits from the health system for all. As a health economics concept, UHC guarantees financial protection by providing a shield against the catastrophic and impoverishing consequences of out-of-pocket expenditure, through the implementation of pooled prepaid financing systems. As a public health concept, UHC has attracted several controversies regarding which services should be covered: comprehensive services vs. minimum basic package, and priority disease-specific interventions vs. primary health care. As a multi dimensional concept, grounded in international human rights laws, the move towards UHC in LMICs requires all states to effectively recognize the right to health in their national constitutions. It also requires a human rights-focused integrated approach to health service delivery that recognizes the health system as a complex phenomenon with interlinked functional units whose effective interaction are essential to reach the equilibrium called UHC. PMID- 26141808 TI - Virtual reality for improving balance in patients after stroke: A systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the effectiveness of virtual reality interventions for improving balance in people after stroke. DESIGN: Systematic review and meta analysis of randomized controlled trials. METHODS: Studies were obtained by searching the following databases: MEDLINE, CINAHL, EMBASE, Web of Science and CENTRAL. Two reviewers assessed studies for inclusion, extracted data and assessed trial quality. RESULTS: Sixteen studies involving 428 participants were included. People who received virtual reality interventions showed marked improvements in Berg Balance Scale (mean difference: 1.46, 95% confidence interval: 0.09-2.83, P<0.05, I2=0%) and Timed Up and Go Test (mean difference: 1.62, 95% confidence interval: -3.07- -0.16, P<0.05, I2=24%) compared with controls. CONCLUSIONS: This meta-analysis of randomized controlled trials supports the use of virtual reality to improve balance after stroke. PMID- 26141809 TI - Common goal areas in the treatment of upper limb spasticity: a multicentre analysis. AB - OBJECTIVE: We aimed to develop a goal classification of individualised goals for spasticity treatment incorporating botulinum toxin intervention for upper limb spasticity to under-pin a more structured approach to future goal setting. DESIGN: Individualised goals for spasticity treatment incorporating botulinum toxin intervention for upper limb spasticity (n=696) were analysed initially from four studies published in 2008-2012, spanning a total of 18 centres (12 in the UK and 6 in Australia). Goals were categorised and mapped onto the closest matching domains of the WHO International Classification of Functioning. Confirmatory analysis included a further 927 goals from a large international cohort study spanning 22 countries published in 2013. RESULTS: Goal categories could be assigned into two domains, each subdivided into three key goal areas: Domain 1: symptoms/impairment n=322 (46%): a. pain/discomfort n=78 (11%), b. involuntary movements n=75 (11%), c. range of movement/contracture prevention n=162 (23%). Domain 2: Activities/function n=374 (54%): a. passive function (ease of caring for the affected limb) n=242 (35%), b active function (using the affected limb in active tasks) n=84 (12%), c. mobility n=11 (2%).Over 99% of the goals from the large international cohort fell into the same six areas, confirming the international applicability of the classification. CONCLUSIONS: Goals for management of upper limb spasticity, in worldwide clinical practice, fall into six main goal areas. PMID- 26141810 TI - Institutional Elderly Care Services and Moroccan and Turkish Migrants in Belgium: A Literature Review. AB - In several European countries, including Belgium, the rapid ageing of the migrant population has emerged only recently on the political agenda. The aim of this literature review is threefold. Firstly, it provides a review of the available studies on the accessibility and use of institutional care services by Moroccan and Turkish migrants in the Flemish part of Belgium including Flanders and Brussels. Secondly, it identifies their specific needs regarding elderly care services. Finally, it provides an overview of the way in which Belgian policy has dealt with the issue of migration and elderly care. Literature published between 1965 and 2014 and relevant to the Belgian context has been included. This search yielded 21 references, of which 8 empirical studies, 5 policy literature, 3 theoretical studies, 3 news articles and 2 popularized reports. Mainstream elderly care remains relatively inaccessible for these migrants due to the language and a series of cultural and religious barriers, a low level of education, financial constraints, a lack of knowledge of health care systems, and the so-called return and care dilemmas. Their religious and cultural needs are currently not met by elderly care services. The inclusive and neutral Belgian policy seems to pay insufficient attention to these issues. PMID- 26141811 TI - The IgG avidity value for the prediction of Toxoplasma gondii infection in the amniotic fluid. AB - Primary Toxoplasma gondii (T. gondii) infection during pregnancy may lead to congenital toxoplasmosis. Maternal screening using T. gondii IgG avidity measurement and multiplex nested PCR was performed. The aim of this prospective cohort study was to determine a cut-off value of IgG avidity index (AI) for the prediction of the presence of T. gondii DNA in the amniotic fluid. One hundred thirty-nine women with positive or equivocal tests for IgM underwent both serum IgG avidity measurement and PCR analysis for the amniotic fluid. Nine had positive PCR results, and three of them were diagnosed as having congenital infection. A cut-off value of IgG AI was determined using receiver operating characteristic analysis. IgG AI (mean 13%) in women with positive PCR results was significantly lower than that (39%) in women with negative results. A cut-off value of <25% IgG AI yields the best results with 77.8% sensitivity and 81.5% specificity for the presence of T. gondii DNA in the amniotic fluid. None of women with IgG AI of >=30% had a positive PCR result or congenital infection. This study firstly demonstrated that a cut-off value of 25-30% IgG AI might be useful for the prediction of the presence of T. gondii DNA in the amniotic fluid and congenital infection. PMID- 26141812 TI - Efficacy and safety of tazobactam/piperacillin as an empirical treatment for the patients of adult and child with febrile neutropenia in Japan. AB - Tazobactam/piperacillin (4.5 g for adults and 90 mg/kg body weight for children, every 6 h) was administered to Japanese patients with febrile neutropenia to evaluate its defervescence and clinical efficacy and safety. The pharmacokinetics in children were also examined. Defervescence efficacy at day 4 of the treatment was achieved in 50.0% of 94 adult and 62.5% of 8 pediatric patients, respectively. The defervescence efficacy rate in relation to the neutrophil count in adults was 37.5% for the patients with a neutrophil count of less than 100/MUL and 62.5% for that between 100 and 500/MUL. The clinical efficacy rate at day 7 and at the end or discontinuation of the treatment was 79.6% and 59.1% in adult patients, respectively, and 57.1% and 75.0% in pediatric patients, respectively. Fifteen strains of causative bacteria were isolated in 13 adult patients at baseline. All strains were eradicated within 4 days of the treatment. The side effects that occurred in adult and pediatric patients during the treatment were all known and not specific to febrile neutropenia patients. The pharmacokinetics profiles of tazobactam/piperacillin in children with febrile neutropenia are unlikely to be different from those in children with a common bacterial infection and without any immunosuppressive conditions. The study results in Japanese patients with febrile neutropenia demonstrate that tazobactam/piperacillin treatment is efficacious and safe in adults. As for pediatric patients, given the limited number of cases studied, further investigation is needed (Clinical trial number: Japic CTI-121728). PMID- 26141813 TI - In vitro efficacy of liposomal amphotericin B, micafungin and fluconazole against non-albicans Candida species biofilms. AB - Non-albicans Candida species are being isolated with increasing frequency. In this study, biofilm formation by Candida tropicalis, Candida parapsilosis and Candida glabrata was evaluated and the activities of liposomal amphotericin B (LAB), micafungin (MFG) and fluconazole (FLC) against these biofilms were assessed using a clinically relevant in vitro model system. LAB exhibited strong activities against the three non-albicans Candida species and showed dose dependent efficacy. MFG displayed a paradoxical growth effect against the C. tropicalis biofilm. FLC was ineffective for non-albicans biofilms. This study shows that Candida biofilms have unique susceptibility to LAB. The dose-dependent effects of LAB indicate that this drug may be a useful treatment for biofilm formation by non-albicans Candida species in cases in which the catheter cannot be removed for clinical reasons. PMID- 26141815 TI - Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model. AB - Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in transient anticonvulsant effects which parallel unesterified DHA serum concentrations. PMID- 26141814 TI - Pharmacokinetics of posaconazole prophylaxis of patients with acute myeloid leukemia. AB - Antifungal prophylaxis is routinely given to patients with hematologic malignancies at high risk for invasive fungal infections (IFI), yet breakthrough IFI may still occur. Posaconazole emerged as an excellent alternative for fungal prophylaxis in high-risk patients. There is limited data about pharmacokinetics and plasma concentrations of posaconazole when given as prophylaxis in patients with hematologic malignancies. We recruited 20 adult patients for prospective, open label trial of posaconazole given as a prophylaxis in patients with newly diagnosed acute myeloid leukemia (AML) undergoing induction chemotherapy or first salvage therapy. The median age of all patients was 65 years and received prophylaxis for a median of 38 days (range: 5-42 days).Ten patients (50%) completed 42 days on posaconazole prophylaxis. Median plasma posaconazole levels showed no statistical difference across gender, body surface area, patients developing IFI, and patients acquiring grade 3 or 4 elevation of liver enzymes. However, there was an overall trend for higher trough concentrations among patients with no IFI than those with IFI. Pharmacokinetics of posaconazole varies from patient to patient, and AML patients receiving induction chemotherapy who never develop IFI tend to have higher plasma concentrations after oral administration of posaconazole. PMID- 26141816 TI - Role of extracellular matrix in development of skeletal muscle and postmortem aging of meat. AB - The integrity of skeletal muscle is maintained by the intramuscular connective tissues (IMCTs) that are composed of extracellular matrix (ECM) molecules such as collagens, proteoglycans, and glycoproteins. The ECM plays an important role not only in providing biomechanical strength of the IMCT, but also in regulating muscle cell behavior. Some ECM molecules, such as decorin and laminin, modulate the activity of myostatin that regulates skeletal muscle mass. Furthermore, it has been shown that decorin activates Akt downstream of insulin-like growth factor-I receptor (IGF-IR) and enhances the differentiation of myogenic cells, suggesting that decorin acts as a signaling molecule to myogenic cells. With animal growth, the structural integrity of IMCT increases; collagen fibrils within the endomysium associate more closely with each other, and the collagen fibers in the perimysium become increasingly thick and their wavy pattern grows more regular. These changes increase the mechanical strength of IMCT, contributing to the toughening of meat. However, in highly marbled beef cattle like Wagyu, intramuscular fat deposits mainly in the perimysium between muscle fiber bundles during the fattening period. The development of adipose tissues appears to disorganize the structure of IMCT and contributes to the tenderness of Wagyu beef. The IMCT was considered to be rather immutable compared to myofibrils during postmortem aging of meat. However, several studies have shown that collagen networks in the IMCT are disintegrated and proteoglycan components are degraded during postmortem aging. These changes in ECM appear to reduce the mechanical strength of IMCT and contribute to the tenderness of uncooked meat or cooked meat at low temperature. Thus, the ECM plays a multifunctional role in skeletal muscle development and postmortem aging of meat. PMID- 26141817 TI - Off-label indications for mifepristone in gynecology and obstetrics. PMID- 26141818 TI - Featured research at the 2015 North American Forum on Family Planning. PMID- 26141819 TI - Association between vitamin D deficiency and methicillin-resistant Staphylococcus aureus infection. AB - PURPOSE: Given that vitamin D (25(OH)D) contributes to immune defense, we sought to determine if deficiency of 25(OH)D was significantly associated with methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: All patients with 25(OH)D determinations at the Atlanta VAMC from 2007 to 2010 were included in the analyses. These patients were cross-referenced with a prospectively collected MRSA infection database at the AVAMC (2006-2010). Patients with one or more MRSA infections during the study period were considered MRSA-infected patients. Multivariate logistic regression was used to determine the association between 25(OH)D status [deficient (<20 ng/mL) vs. non-deficient (>=20 ng/mL)] and MRSA infection. RESULTS: A total of 6405 patients with 25(OH)D determinations were included in the analyses, of which 401 (6.3 %) were MRSA infected patients. Mean (SD) vitamin D levels, in ng/mL, were 21.1 (12.4) and 24.0 (12.6) for MRSA-infected patients and non-MRSA infected patients, respectively (p < 0.0001). The multivariate logistic regression model confirmed associations between MRSA infection and sex, race, BMI, HIV status, and 25(OH)D [odds ratio for 25(OH)D: 1.94; 95 % confidence interval: 1.51-2.49]. CONCLUSION: MRSA-infected patients had significantly lower serum vitamin D levels than non MRSA infected patients, even when controlling for potential confounding variables. PMID- 26141820 TI - Late-onset cytomegalovirus infection complicated by Guillain-Barre syndrome in a kidney transplant recipient: case report and review of the literature. AB - Cytomegalovirus (CMV) infection remains a common infection after solid-organ transplantation. In the general population CMV disease is associated with Guillain-Barre syndrome (GBS), an autoimmune disease leading to an acute peripheral neuropathy, in 1 of 1000 cases. Interestingly, GBS is a rarely observed complication in solid-organ transplant recipients, possibly related to maintenance immunosuppression. We describe a case of CMV infection complicated by GBS in a kidney transplant recipient and review the literature. PMID- 26141821 TI - Unplanned reaction or something else? The role of subjective cultures in hazardous and harmful drinking. AB - This study compares the impact of levels of impulsivity and subjective cultures through which subjects interpret their experience of the social environment on the probability of hazardous and harmful alcohol use. A sample of 501 participants from Southern Italy completed a series of questionnaires in order to detect their subjective cultures and levels of impulsiveness (attentional, motor and non-planning). Moreover, alcohol consumption, drinking behavior, alcohol related problems and adverse reactions during the past year were assessed. A sub group of hazardous and harmful drinkers (n = 106; 21%) was identified and a healthy control group (n = 127; 25%) was selected. Members of the hazardous and harmful group view the social environment as a significantly more unreliable place, and also scored higher on motor impulsiveness and lower on non-planning impulsiveness. Discussion considers theoretical and clinical implications of the results. PMID- 26141823 TI - Re: Outcomes of Endoscopic Incision for the Treatment of Ureterocele in Children at a Single Institution: J. C. Sander, A. N. Bilgutay, I. Stanasel, C. J. Koh, N. Janzen, E. T. Gonzales, D. R. Roth and A. Seth J Urol 2015;193:662-667. PMID- 26141822 TI - Refined analysis of the Campylobacter jejuni iron-dependent/independent Fur- and PerR-transcriptomes. AB - BACKGROUND: The genome of Campylobacter jejuni contains two iron activated Fur family transcriptional regulators, CjFur and CjPerR, which are primarily responsible for regulating iron homeostasis and oxidative stress respectively. Both transcriptional regulators have been previously implicated in regulating diverse functions beyond their primary roles in C. jejuni. To further characterize their regulatory networks, RNA-seq was used to define the transcriptional profiles of C. jejuni NCTC11168 wild type, Deltafur, DeltaperR and DeltafurDeltaperR isogenic deletion mutants under both iron-replete and iron limited conditions. RESULTS: It was found that 202 genes were differentially expressed in at least one mutant under iron-replete conditions and 331 genes were differentially expressed in at least one mutant under iron-limited conditions. The CjFur and CjPerR transcriptomes characterized in this study were compared to those previously identified using microarray profiling and found to be more extensive than previously understood. Interestingly, our results indicate that CjFur/CjPerR appear to co-regulate the expression of flagellar biogenesis genes in an opposing and iron-independent fashion. Moreover the DeltafurDeltaperR isogenic deletion mutant revealed that CjFur and CjPerR can compensate for each other in certain cases, suggesting that both regulators may compete for binding to specific promoters. CONCLUSIONS: The CjFur and CjPerR transcriptomes are larger than previously reported. In particular, deletion of perR results in the differential expression of a large group of genes in the absence of iron, suggesting that CjPerR may also regulate genes in an iron-independent manner, similar to what has already been demonstrated with CjFur. Moreover, subsets of genes were found which are only differentially expressed when both CjFur and CjPerR are deleted and includes genes that appear to be simultaneously activated by CjFur and repressed by CjPerR. In particular the iron-independent co regulation of flagellar biogenesis by CjFur/CjPerR represents a potentially novel regulatory function for these proteins. These findings represent additional modes of co-regulation by these two transcriptional regulators in C. jejuni. PMID- 26141824 TI - Re: Mortality after Bladder Augmentation in Children with Spina Bifida: K. M. Szymanski, R. Misseri, B. Whittam, C. M. Adams, J. Kirkegaard, S. King, M. Kaefer, R. C. Rink and M. P. Cain J Urol 2015; 193: 643-648. PMID- 26141825 TI - Common neuropathological features underlie distinct clinical presentations in three siblings with hereditary diffuse leukoencephalopathy with spheroids caused by CSF1R p.Arg782His. AB - Hereditary diffuse leukoencephalopathy with spheroids (HDLS) presents with a variety of clinical phenotypes including motor impairments such as gait dysfunction, rigidity, tremor and bradykinesia as well as cognitive deficits including personality changes and dementia. In recent years, colony stimulating factor 1 receptor gene (CSF1R) has been identified as the primary genetic cause of HDLS. We describe the clinical and neuropathological features in three siblings with HDLS and the CSF1R p.Arg782His (c.2345G > A) pathogenic mutation. Each case had varied motor symptoms and clinical features, but all included slowed movements, poor balance, memory impairment and frontal deficits. Neuroimaging with magnetic resonance imaging revealed atrophy and increased signal in the deep white matter. Abundant white matter spheroids and CD68 positive macrophages were the predominant pathologies in these cases. Similar to other cases reported in the literature, the three cases described here had varied clinical phenotypes with a pronounced, but heterogeneous distribution of axonal spheroids and distinct microglia morphology. Our findings underscore the critical importance of genetic testing for establishing a clinical and pathological diagnosis of HDLS. PMID- 26141826 TI - A priori Linfinity estimates for solutions of a class of reaction-diffusion systems. AB - In this short paper, we establish a priori Linfinity-norm estimates for solutions of a class of reaction-diffusion systems which can be used to model the spread of infectious disease. The developed technique may find applications in other reaction-diffusion systems. PMID- 26141828 TI - Understanding tissue expression evolution: from expression phylogeny to phylogenetic network. AB - Our understanding of tissue expression evolution in multi-cellular model organisms has been considerably advanced with the help of high-throughput technologies from EST, microarray to RNA-seq. Yet, many controversies remained unsolved, ranging from the evolutionary patterns of tissue expressions to expression phylogenetic analysis. Moreover, despite numerous reports published, it is desirable to have a general framework for study of tissue expression evolution. In this article, we first provide an up-to-date and concise review for the study of tissue expression evolution in multi-cellular organisms. While the expression phylogeny of the same tissues sampled from closely or intermediately related species largely reflects the species phylogeny, we demonstrate that phylogenetic network approach may shed some lights for our understanding of the developmental similarity and evolutionary relatedness during the multi-tissue evolution. PMID- 26141827 TI - Improving protein identification from tandem mass spectrometry data by one-step methods and integrating data from other platforms. AB - MOTIVATION: Many approaches have been proposed for the protein identification problem based on tandem mass spectrometry (MS/MS) data. In these experiments, proteins are digested into peptides and the resulting peptide mixture is subjected to mass spectrometry. Some interesting putative peptide features (peaks) are selected from the mass spectra. Following that, the precursor ions undergo fragmentation and are analyzed by MS/MS. The process of identification of peptides from the mass spectra and the constituent proteins in the sample is called protein identification from MS/MS data. There are many two-step protein identification procedures, reviewed in the literature, which first attempt to identify the peptides in a separate process and then use these results to infer the proteins. However, in recent years, there have been attempts to provide a one step solution to protein identification, which simultaneously identifies the proteins and the peptides in the sample. RESULTS: In this review, we briefly introduce the most popular two-step protein identification procedure, PeptideProphet coupled with ProteinProphet. Following that, we describe the difficulties with two-step procedures and review some recently introduced one step protein/peptide identification procedures that do not suffer from these issues. The focus of this review is on one-step procedures that are based on statistical likelihood-based models, but some discussion of other one-step procedures is also included. We report comparative performances of one-step and two-step methods, which support the overall superiorities of one-step procedures. We also cover some recent efforts to improve protein identification by incorporating other molecular data along with MS/MS data. PMID- 26141829 TI - Practical analysis of specificity-determining residues in protein families. AB - Determining the residues that are important for the molecular activity of a protein is a topic of broad interest in biomedicine and biotechnology. This knowledge can help understanding the protein's molecular mechanism as well as to fine-tune its natural function eventually with biotechnological or therapeutic implications. Some of the protein residues are essential for the function common to all members of a family of proteins, while others explain the particular specificities of certain subfamilies (like binding on different substrates or cofactors and distinct binding affinities). Owing to the difficulty in experimentally determining them, a number of computational methods were developed to detect these functional residues, generally known as 'specificity-determining positions' (or SDPs), from a collection of homologous protein sequences. These methods are mature enough for being routinely used by molecular biologists in directing experiments aimed at getting insight into the functional specificity of a family of proteins and eventually modifying it. In this review, we summarize some of the recent discoveries achieved through SDP computational identification in a number of relevant protein families, as well as the main approaches and software tools available to perform this type of analysis. PMID- 26141830 TI - Using prior knowledge from cellular pathways and molecular networks for diagnostic specimen classification. AB - For many complex diseases, an earlier and more reliable diagnosis is considered a key prerequisite for developing more effective therapies to prevent or delay disease progression. Classical statistical learning approaches for specimen classification using omics data, however, often cannot provide diagnostic models with sufficient accuracy and robustness for heterogeneous diseases like cancers or neurodegenerative disorders. In recent years, new approaches for building multivariate biomarker models on omics data have been proposed, which exploit prior biological knowledge from molecular networks and cellular pathways to address these limitations. This survey provides an overview of these recent developments and compares pathway- and network-based specimen classification approaches in terms of their utility for improving model robustness, accuracy and biological interpretability. Different routes to translate omics-based multifactorial biomarker models into clinical diagnostic tests are discussed, and a previous study is presented as example. PMID- 26141831 TI - Editorial Introduction. PMID- 26141832 TI - Case Report: A Systems Approach to Genetic Counseling for Albinism. AB - A systems approach to family therapy assumes that a person and his/her problems do not operate in a social vacuum but instead are imbedded in a social context. This context includes fairly small social systems such as a nuclear family and larger social systems such as school systems and cultural beliefs. A case of a girl with albinism born to a couple from India will be used to discuss how a systems approach might be useful in a genetic counseling setting. PMID- 26141834 TI - Genetic Library. PMID- 26141833 TI - Commentary on "A Systems Approach to Genetic Counseling for Albinism". PMID- 26141835 TI - Zn/Ag micro-galvanic couples formed on titanium and osseointegration effects in the presence of S. aureus. AB - Titanium implants possessing simultaneous osseointegration and antibacterial ability are desirable. In this work, three types of Zn/Ag micro-galvanic couples are fabricated on titanium by plasma immersion ion implantation to investigate the osseointegration and antibacterial effects as well as the involved mechanisms. The in vitro findings disclose enhanced proliferation, osteogenic differentiation, and gene expressions of the rat bone mesenchymal stem cells (rBMSCs), as well as good antibacterial ability on all three micro-galvanic couples. Excellent antimicrobial ability is also observed in vivo and the micro CT and histological results reveal notable osseointegration in vivo despite the presence of bacteria. The Zn/Ag micro-galvanic couple formed on Zn/Ag dual-ion co implanted titanium shows the best osseointegration as well as good antibacterial properties in vivo obtained from a rabbit tibia model. The difference among the three Zn/Ag micro-galvanic couples can be ascribed to the contact between the Ag NPs and Zn film, which affects the corrosion process. Our results indicate that the biological behavior can be controlled by the corrosion process of the Zn/Ag micro-galvanic couples. PMID- 26141837 TI - Comparison of proximal femur and vertebral body strength improvements in the FREEDOM trial using an alternative finite element methodology. AB - Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.6%) strength in sideways fall configuration at 36 months, estimated in Newtons by an established voxel-based finite element (FE) methodology. Since FE analyses rely on the choice of meshes, material properties, and boundary conditions, the aim of this study was to independently confirm and compare the effects of denosumab on vertebral and femoral strength during the FREEDOM trial using an alternative smooth FE methodology. Unlike the previous FE study, effects on femoral strength in physiological stance configuration were also examined. QCT data for the proximal femur and two lumbar vertebrae were analyzed by smooth FE methodology at baseline, 12, 24, and 36 months for 51 treated (denosumab) and 47 control (placebo) subjects. QCT images were segmented and converted into smooth FE models to compute bone strength. L1 and L2 vertebral bodies were virtually loaded in axial compression and the proximal femora in both fall and stance configurations. Denosumab increased vertebral body strength by 10.8%, 14.0%, and 17.4% from baseline at 12, 24, and 36 months, respectively (p<0.0001). Denosumab also increased femoral strength in the fall configuration by 4.3%, 5.1%, and 7.2% from baseline at 12, 24, and 36 months, respectively (p<0.0001). Similar improvements were observed in the stance configuration with increases of 4.2%, 5.2%, and 5.2% from baseline (p<=0.0007). Differences between the increasing strengths with denosumab and the decreasing strengths with placebo were significant starting at 12 months (vertebral and femoral fall) or 24 months (femoral stance). Using an alternative smooth FE methodology, we confirmed the significant improvements in vertebral body and proximal femur strength previously observed with denosumab. Estimated increases in strength with denosumab and decreases with placebo were highly consistent between both FE techniques. PMID- 26141836 TI - Nano-hydroxyapatite modulates osteoblast lineage commitment by stimulation of DNA methylation and regulation of gene expression. AB - Hydroxyapatite (HA) is the primary structural component of the skeleton and dentition. Under biological conditions, HA does not occur spontaneously and therefore must be actively synthesized by mineralizing cells such as osteoblasts. The mechanism(s) by which HA is actively synthesized by cells and deposited to create a mineralized matrix are not fully understood and the consequences of mineralization on cell function are even less well understood. HA can be chemically synthesized (HAp) and is therefore currently being investigated as a promising therapeutic biomaterial for use as a functional scaffold and implant coating for skeletal repair and dental applications. Here we investigated the biological effects of nano-HAp (10 * 100 nm) on the lineage commitment and differentiation of bone forming osteoblasts. Exposure of early stage differentiating osteoblasts resulted in dramatic and sustained changes in gene expression, both increased and decreased, whereas later stage osteoblasts were much less responsive. Analysis of the promoter region one of the most responsive genes, alkaline phosphatase, identified the stimulation of DNA methylation following cell exposure to nano-HAp. Collectively, the results reveal the novel epigenetic regulation of cell function by nano-HAp which has significant implication on lineage determination as well as identifying a novel potential therapeutic use of nanomaterials. PMID- 26141838 TI - MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation. AB - Glucocorticoid treatment reportedly increases the morbidity of osteoporotic or osteonecrotic disorders. Exacerbated bone acquisition and escalated marrow adipogenesis are prominent pathological features of glucocorticoid-mediated skeletal disorders. MicroRNAs reportedly modulate tissue metabolism and remodeling. This study was undertaken to investigate the biological roles of microRNA-29a (miR-29a) in skeletal and fat metabolism in the pathogenesis of glucocorticoid-induced osteoporosis. Transgenic mice overexpressing miR-29a precursor or wild-type mice were given methylprednisolone. Bone mass, microarchitecture and histology were assessed by dual energy X-ray absorptiometry, MUCT and histomorphometry. Differential gene expression and signaling components were delineated by quantitative RT-PCR and immunoblotting. Glucocorticoid treatment accelerated bone loss and marrow fat accumulation in association with decreased miR-29a expression. The miR-29a transgenic mice had high bone mineral density, trabecular microarchitecture and cortical thickness. miR-29a overexpression mitigated the glucocorticoid-induced impediment of bone mass, skeletal microstructure integrity and mineralization reaction and attenuated fatty marrow histopathology. Ex vivo, miR-29a increased osteogenic differentiation capacity and alleviated the glucocorticoid-induced promotion of adipocyte formation in primary bone-marrow mesenchymal progenitor cell cultures. Through inhibition of histone deacetylase 4 (HDAC4) expression, miR-29a restored acetylated Runx2 and beta-catenin abundances and reduced RANKL, leptin and glucocorticoid receptor expression in glucocorticoid-mediated osteoporosis bone tissues. Taken together, glucocorticoid suppression of miR-29a signaling disturbed the balances between osteogenic and adipogenic activities, and thereby interrupted bone formation and skeletal homeostasis. miR-29a inhibition of HDAC4 stabilized the acetylation state of Runx2 and beta-catenin that ameliorated the detrimental effects of glucocorticoid on mineralization and lipogenesis reactions in bone tissue microenvironments. This study highlighted emerging skeletal anabolic actions of miR-29a signaling in the progression of glucocorticoid induced bone tissue destruction. Sustaining miR-29a actions is beneficial in protecting against glucocorticoid-mediated osteoporosis. PMID- 26141839 TI - Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation. AB - To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and alphaSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that alphaSMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the alphaSMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. PMID- 26141840 TI - Sex- and afferent-specific differences in histamine receptor expression in vagal afferents of rats: A potential mechanism for sexual dimorphism in prevalence and severity of asthma. AB - The incidence of asthma is more common in boys than in girls during the childhood, and more common in premenopausal female than age-matched males. Our previous study demonstrated a gender difference in histamine-mediated neuroexcitability in nodose ganglia neurons (NGNs), highlighting a possibility of histamine-mediated gender difference in asthma via visceral afferent function. In the present study, we aimed to explore the gender difference in expression profiles of histamine receptors (HRs) in nodose ganglia (NG) and individual identified NGNs to provide deeper insights into the mechanisms involved in sexual dimorphism of asthma. Western-blot and SYBR green RT-PCR showed that H2R and H3R were highly expressed in NG of females compared with males and downregulated in ovariectomized females. H1R was equally expressed in NG of both sexes and not altered by ovariectomy. Furthermore, this highly expressive H2R and H3R were distributed in both myelinated and unmyelinated NGNs isolated from adult female rats by immunofluorescence and single-cell RT-PCR. H3R widely distributed in all tested neuron subtypes and its expression did not show significant difference among neuron subtypes. H2R was widely and highly expressed in low-threshold and sex-specific subpopulation of myelinated Ah-types compared with myelinated A- and unmyelinated C-type NGNs. Unexpectedly, weak expression of H1R was detected in both myelinated and unmyelinated NGNs by immunofluorescence, which was further confirmed by single-cell RT-PCR. Our results suggest that the sexual dimorphism in the expression of H2R and H3R in vagal afferents very likely contributes, at least partially, to the gender difference in prevalence and severity of asthma. PMID- 26141841 TI - Cognitive impairment and morphological changes in the dorsal hippocampus of very old female rats. AB - The hippocampus, a medial temporal lobe structure necessary for the formation of spatial memory, is particularly affected by both normal and pathologic aging. In previous studies, we observed a significant age-related increase in dopaminergic neuron loss in the hypothalamus and the substantia nigra of female rats, which becomes more conspicuous at extreme ages. Here, we extend our studies by assessing spatial memory in 4-6 month-old (young), 26-month-old (old) and 29-32 month-old (senile) Sprague-Dawley female rats as well as the age-related histopathological changes in their dorsal hippocampus. Age changes in spatial memory performance were assessed with a modified version of the Barnes maze test. We employed two probe trials (PTs), one and five days after training, respectively, in order to evaluate learning ability as well as short-term and longer-term spatial memory retention. A set of relevant hippocampal cell markers was also quantitated in the animals by means of an unbiased stereological approach. The results revealed that old rats perform better than senile rats in acquisition trials and young rats perform better than both aging groups. However, during short-term PT both aging groups showed a preserved spatial memory while in longer-term PT, spatial memory showed deterioration in both aged groups. Morphological analysis showed a marked decrease (94-97%) in doublecortin neuron number in the dentate gyrus in both aged groups and a reduction in glial fibrillary acidic protein-positive cell number in the stratum radiatum of aging rats. Astroglial process length and branching complexity decreased in aged rats. We conclude that while target-seeking activity and learning ability decrease in aged females, spatial memory only declines in the longer-term tests. The reduction in neuroblast number and astroglial arborescence complexity in the dorsal hippocampus are likely to play a role in the cognitive deficits of aging rats. PMID- 26141843 TI - Enhanced nonsynaptic epileptiform activity in the dentate gyrus after kainate induced status epilepticus. AB - Understanding the mechanisms that influence brain excitability and synchronization provides hope that epileptic seizures can be controlled. In this scenario, non-synaptic mechanisms have a critical role in seizure activity. The contribution of ion transporters to the regulation of seizure-like activity has not been extensively studied. Here, we examined how non-synaptic epileptiform activity (NEA) in the CA1 and dentate gyrus (DG) regions of the hippocampal formation were affected by kainic acid (KA) administration. NEA enhancement in the DG and suppression in area CA1 were associated with increased NKCC1 expression in neurons and severe neuronal loss accompanied by marked glial proliferation, respectively. Twenty-four hours after KA, the DG exhibited intense microglial activation that was associated with reduced cell density in the infra pyramidal lamina; however, cellular density recovered 7 days after KA. Intense Ki67 immunoreactivity was observed in the subgranular proliferative zone of the DG, which indicates new neuron incorporation into the granule layer. In addition, bumetanide, a selective inhibitor of neuronal Cl(-) uptake mediated by NKCC1, was used to confirm that the NKCC1 increase effectively contributed to NEA changes in the DG. Furthermore, 7 days after KA, prominent NKCC1 staining was identified in the axon initial segments of granule cells, at the exact site where action potentials are preferentially initiated, which endowed these neurons with increased excitability. Taken together, our data suggest a key role of NKCC1 in NEA in the DG. PMID- 26141842 TI - Endocannabinoid signaling mechanisms in the substantia nigra pars reticulata modulate GABAergic nigrotectal pathways in mice threatened by urutu-cruzeiro venomous pit viper. AB - The substantia nigra pars reticulata (SNpr) is rich in gamma-aminobutyric acid (GABA)-ergic neurons and connected to the mesencephalic tectum (MT) structures, such as the superior colliculus and dorsal periaqueductal gray matter. The SNpr presents a high density of cannabinoid receptors (CBRs), suggesting a possible regulatory role that is played by endocannabinoids (eCBs) in the ventral mesencephalon. The present study investigated the involvement of SNpr eCB mechanisms in nigrotectal pathways in the expression of defensive behavior associated with instinctive fear and panic reactions in mice that are confronted with the venomous Viperidae snake Bothrops alternatus. The localization of CB1 receptors (CB1RS) and synaptophysin glycoprotein in the SNpr was also evaluated. Administration of the GABAA receptor antagonist bicuculline in the MT increased defensive responses to the snake that are related to panic, such as freezing and non-oriented escape reactions, sometimes toward the snake itself. Mice that were pretreated with anandamide (5 or 50pmol) in the SNpr, followed by an injection of physiological saline or bicuculline in the MT, exhibited significant decreases in the expression of alertness, freezing, and escape responses. Immunofluorescence showed the presence of fibers that were rich in CB1RS and synaptophysin in the SNpr, indicating that these receptors appear to be located mainly in presynaptic terminals in the striatonigral pathway. These findings suggest that eCB mechanisms in the SNpr facilitate the activity of nigrotectal GABAergic pathways, modulating the activity of striatonigral links during the elaboration and organization of innate fear and panic-like responses in threatening situations. PMID- 26141844 TI - Function of the centromedial amygdala in reward devaluation and open-field activity. AB - The present research aimed at determining the role played by the amygdala in reward devaluation using transient inactivation induced by lidocaine microinfusions into the centromedial region. Two situations involving reward devaluation were tested in rats: consummatory successive negative contrast (cSNC) and anticipatory negative contrast (ANC). In cSNC, rats exposed to a downshift from 32% to 4% sucrose consume less 4% sucrose than rats always exposed to 4% sucrose. Extensive evidence suggests that reward devaluation in the cSNC situation is accompanied by negative emotion. In ANC, rats consume less 4% sucrose when each session is closely followed by access to 32% sucrose rather than by 4% sucrose. Evidence suggests that reward devaluation in the ANC situation does not involve negative emotions; rather, ANC appears to involve Pavlovian anticipation of the higher value solution. To test the effects of lidocaine microinfusions in a situation known to induce negative emotion, but unrelated to reward devaluation, animals were also exposed to a lighted open field. Centromedial amygdala inactivation reduced the cSNC effect and increased exploratory behavior in the open field, both effects consistent with a reduction in negative emotional state. However, no detectable effects of amygdala inactivation were observed in the ANC situation. These results suggest that, first, the function of the amygdala is not unique to reward devaluation and, second, it is concerned with tagging the devaluation experience with aversive valence. PMID- 26141845 TI - Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. AB - Glucagon-like peptide 1 (GLP-1) is a growth factor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a clinical trial in PD patients showed promising first results. Liraglutide and lixisenatide are two newer GLP-1 mimetics which have a longer biological half-life than exendin-4. We previously showed that these drugs have neuroprotective properties in an animal model of Alzheimer's disease. Here we demonstrate the neuroprotective effects in the 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20mg/kg i.p.) for 7 days, and drugs were injected once-daily for 14 days i.p. When comparing exendin-4 (10 nmol/kg), liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen. Both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The results demonstrate that in this study, both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of PD. PMID- 26141846 TI - Melatonin modulates M4-type ganglion-cell photoreceptors. AB - In the retina, melatonin is secreted at night by rod/cone photoreceptors and serves as a dark-adaptive signal. Melatonin receptors have been found in many retinal neurons including melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting it could modulate the physiology of these inner retinal photoreceptors. Here, we investigated whether melatonin modulates the alpha-like M4-type ipRGCs, which are believed to mediate image forming vision as well as non-image-forming photoresponses. Applying melatonin during daytime (when endogenous melatonin secretion is low) caused whole-cell recorded M4 cells' rod/cone-driven depolarizing photoresponses to become broader and larger, whereas the associated elevation in spike rate was reduced. Melanopsin-based light responses were not affected significantly. Nighttime application of the melatonin receptor antagonist luzindole also altered M4 cells' rod/cone-driven light responses but in the opposite ways: the duration and amplitude of the graded depolarization were reduced, whereas the accompanying spiking increase was enhanced. These luzindole-induced changes confirmed that M4 cells are modulated by endogenous melatonin. Melatonin could induce the above effects by acting directly on M4 cells because immunohistochemistry detected MT1 receptors in these cells, although it could also act presynaptically. Interestingly, the daytime and nighttime recordings showed significant differences in resting membrane potential, spontaneous spike rate and rod/cone driven light responses, suggesting that M4 cells are under circadian control. This is the first report of a circadian variation in ipRGCs' resting properties and synaptic input, and of melatoninergic modulation of ipRGCs. PMID- 26141847 TI - Anxiogenic drug administration and elevated plus-maze exposure in rats activate populations of relaxin-3 neurons in the nucleus incertus and serotonergic neurons in the dorsal raphe nucleus. AB - Anxiety is a complex and adaptive emotional state controlled by a distributed and interconnected network of brain regions, and disruption of these networks is thought to give rise to the behavioral symptoms associated with anxiety disorders in humans. The dorsal raphe nucleus (DR), which contains the majority of forebrain-projecting serotonergic neurons, is implicated in the control of anxiety states and anxiety-related behavior via neuromodulatory effects on these networks. Relaxin-3 is the native neuropeptide ligand for the Gi/o-protein coupled receptor, RXFP3, and is primarily expressed in the nucleus incertus (NI), a tegmental region immediately caudal to the DR. RXFP3 activation has been shown to modulate anxiety-related behavior in rodents, and RXFP3 mRNA is expressed in the DR. In this study, we examined the response of relaxin-3-containing neurons in the NI and serotonergic neurons in the DR following pharmacologically induced anxiety and exposure to an aversive environment. We administered the anxiogenic drug FG-7142 or vehicle to adult male Wistar rats and, 30 min later, exposed them to either the elevated plus-maze or home cage control conditions. Immunohistochemical detection of c-Fos was used to determine activation of serotonergic neurons in the DR and relaxin-3 neurons in the NI, measured 2h following drug injection. Analysis revealed that FG-7142 administration and exposure to the elevated plus-maze are both associated with an increase in c-Fos expression in relaxin-3-containing neurons in the NI and in serotonergic neurons in dorsal and ventrolateral regions of the DR. These data are consistent with the hypothesis that relaxin-3 systems in the NI and serotonin systems in the DR interact to form part of a network involved in the control of anxiety-related behavior. PMID- 26141848 TI - Intraocular pressure changes during hemodialysis. AB - The response of intraocular pressure (IOP) to hemodialysis procedure has been a subject of research throughout many decades. Several studies that evaluated the impact of hemodialysis (HD) on IOP have reported conflicting results and have drawn varied conclusions. Some studies have described an IOP elevation during HD, a finding they attributed to the osmotic disequilibrium between serum and aqueous humor induced by the HD procedure, especially when the facility of the outflow system is already compromised. On the other hand, several studies have reported a significant IOP decrease during HD. The majority of these studies supported the notion that the increase in plasma colloid pressure induced by fluid removal during the HD session is the underlying cause of decreased IOP. Finally, recent investigations did not establish a significant change in IOP measurements during HD. They have therefore suggested that improved dialysis techniques, such as high flux HD, or hemofiltration and better urea control, maintain better osmolar balance and prevent a marked IOP elevation. Nevertheless, specific preventive measures are still necessary in HD patients with ocular pathologies (e.g., glaucoma) whose vision may be adversely influenced by significant IOP fluctuation. PMID- 26141849 TI - Sacral Nerve Stimulation for Pediatric Lower Urinary Tract Dysfunction: Development of a Standardized Pathway with Objective Urodynamic Outcomes. AB - PURPOSE: We propose that sacral nerve stimulation is a valid adjunctive therapy for refractory pediatric lower urinary tract dysfunction, and that prospective collection of preoperative and postoperative validated questionnaires and urodynamic data in a standardized fashion is beneficial in characterizing patient response. MATERIALS AND METHODS: Patients were candidates for sacral nerve stimulation if they had refractory voiding dysfunction and standard treatments had failed. Preoperative evaluation included urodynamic studies, spinal magnetic resonance imaging, and validated bladder and bowel related questionnaires. Children were stratified into 2 groups, ie overactive bladder with or without incontinence (group 1) and detrusor underactivity/urinary retention requiring clean intermittent catheterization (group 2). A staged procedure was used with initial test lead placement, followed by permanent device insertion 2 weeks later if patients demonstrated symptom improvement with test lead. Postoperatively children were followed with questionnaires and at least 1 urodynamic study. RESULTS: A total of 26 children underwent sacral nerve stimulation. Mean patient age was 10.8 years and median followup was 1.2 years. There were 23 patients in group 1 and 4 in group 2 (1 patient was included in both groups). In group 1 voiding dysfunction scores improved significantly, and urodynamic studies revealed a significant decrease in mean number of uninhibited contractions and maximum detrusor pressure during the filling phase. In group 2 there was significant improvement in mean post-void residual. CONCLUSIONS: Sacral nerve stimulation is a treatment option that may produce significant improvement in objective and subjective measures of bladder function in children with refractory lower urinary tract dysfunction. PMID- 26141850 TI - Orchiopexy without Transparenchymal Fixation Suturing: A 29-Year Experience. AB - PURPOSE: We sought to gain insight into the outcomes of nontunical orchiopexy through assessment of elective and emergent orchiopexies performed by a single surgeon from 1985 to 2014. We demonstrate that successful orchiopexy does not require a fixation suture that pierces the tunica albuginea. MATERIALS AND METHODS: We retrospectively analyzed 1,104 orchiopexies in patients 1 day to 25 years old performed by a single urologist during a 29-year period. A total of 155 procedures were performed in 101 patients to remedy torsion, and 949 procedures were performed in 778 patients for undescended testes. The orchiopexy method for all patients was the same, involving no transparenchymal fixation suture. Operative notes, followup appointments and long-term testicular condition were analyzed. Appropriate testicular size and position were considered successful outcomes. Testicular atrophy, suprascrotal location, torsion and long-term pain were considered undesired outcomes. RESULTS: Of the 1,104 orchiopexy cases evaluated 1,090 were deemed successful, with normal testicular position and size postoperatively. A total of 14 testes in 8 patients showed undesired outcomes (postoperative atrophy in 4 testes, long-term pain in 2 and failure to retain appropriate position postoperatively in 8). CONCLUSIONS: Orchiopexy avoiding transparenchymal suturing through the tunica albuginea is a successful approach for fixation of the testis in the scrotum. Considering the high rate of favorable outcomes with this technique, and assuming that tunical invasion negatively impacts spermatogenesis, we consider a tunical suture unnecessary. PMID- 26141851 TI - The Impact of Urethral Risk Factors on Transcorporeal Artificial Urinary Sphincter Erosion Rates and Device Survival. AB - PURPOSE: We report the impact of urethral risk factors on erosion rates and device survival outcomes after transcorporeal artificial urinary sphincter placement. MATERIALS AND METHODS: We performed a retrospective analysis of all transcorporeal artificial urinary sphincters placed at a single institution between January 2000 and May 2014. We assessed patient demographic, comorbid diseases and surgical characteristics for risk factors considered poor for device survival. Risk factors were compared to postoperative complications requiring explantation, including cuff erosion, infection and device revision. RESULTS: A total of 37 transcorporeal artificial urinary sphincters were placed in 35 men. Placement was performed as a primary procedure in 21 of 37 cases (56.8%) and as salvage in the remainder. In this transcorporeal population there were 7 explantations (18.9%) due to erosion in 4 cases, cuff downsizing in 2 and infection in 1. Median followup from implantation to last followup was 8.5 months (range 0.9 to 63). Median time from artificial urinary sphincter placement to explantation was 17.3 months (range 0.9 to 63) and time specifically to transcorporeal erosion was 7.4 months (range 0.9 to 26). On univariate analysis no parameters were associated with sphincter cuff erosion but a history of an inflatable penile prosthesis was associated with a higher device explantation rate (60% vs 12.5%, p=0.04). No associations were revealed on multivariate logistic analysis. All 4 cuff erosion cases demonstrated greater than 2 urethral risk factors, including prior radiation therapy in all. The probability of cuff erosion in patients with 2 or more urethral risk factors was 1.65 times the probability of erosion in those with 0 or 1 urethral risk factor (95% CI 1.3, 2.2). The proportion of patients free of erosion at 35 months was 100% in those with 0 or 1 urethral risk factor and 64% in those with 2 or more risk factors (log rank test p=0.00). Similarly the proportion of patients free of explantation at 35 months was 100% in those with 0 or 1 urethral risk factor and 52% in those with 2 or more (log rank test p=0.02). CONCLUSIONS: Transcorporeal artificial urinary sphincter implantation is generally reserved for complex and high risk cases but favorable functional results were demonstrated. However, patients with multiple urethral risk factors face a higher risk of erosion and device loss. PMID- 26141852 TI - Combined MRI and MRS improves pre-therapeutic diagnoses of pediatric brain tumors over MRI alone. AB - INTRODUCTION: The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. METHODS: Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. RESULTS: Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10% the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27% of cases the reports were wrong. For group B, the diagnoses were correct in 87%, partially correct in 5%, and incorrect in 8% of the cases, which is a significant improvement (p < 0.005). Re-review of combined MRI and MRS of group A resulted 87% correct, 7% partially correct, and 7% incorrect diagnoses, which is a significant improvement over the original diagnoses (p < 0.05). CONCLUSION: Adding MRS to conventional MRI significantly improved diagnostic accuracy in preoperative pediatric patients with untreated brain tumors. PMID- 26141853 TI - US sees first measles death in 12 years. PMID- 26141854 TI - Left atrial appendage isolation using percutaneous (endocardial/epicardial) devices: Pre-clinical and clinical experience. AB - Atrial fibrillation (AF) is the most common arrhythmia in the elderly population and it is associated with a four-fold to five-fold increased risk of thromboembolic events. It was not until the mid-1950s that the left atrial appendage (LAA) was identified as the main location of thrombus formation, particularly in patients with non-valvular AF. In this review, we explain at some extent its embryology, anatomy and physiology, and as well as the clinical and pre-clinical trials published to date testing the safety and efficacy of most LAA closure devices. Among those devices, the most studied include the PLAATO system (ev3 Endovascular, Plymouth, MN), the Amplatzer cardiac plug (St Jude, Golden Valley, MN; St. Jude Medical, Minneapolis, MN), the WATCHMAN device (Boston Scientific, Plymouth, MN; Atritech Inc., Plymouth, MN), and the LARIAT device (SentreHEART, Palo Alto, CA). Similarly, newer LAA closure devices currently under investigation such as the Transcatheter Patch (Custom Medical Devices, Athens, Greece), AEGIS, and the Coherex WaveCrest (Salt Lake City, UT) will also be discussed. Future perspectives and the need for well-designed prospective studies between devices and new oral anticoagulant drugs are also proposed. PMID- 26141855 TI - Epigenetic regulation of Dnmt3a and Arc gene expression after electroconvulsive stimulation in the rat. AB - Electroconvulsive therapy (ECT) remains one of the most effective treatments of major depression. Unfortunately, some patients report side effects, of which the most prominent are memory deficits. The immediate early gene Arc plays a critical role in the maintenance phase of long-term potentiation and consolidation of memory in the rat brain. We recently observed increased methylation of the Arc promoter 24h after acute electroconvulsive stimulation (ECS) in rats, which could cause decreased Arc expression and provide an explanation for the observed memory deficits. In the present study we investigated the methylation and expression changes of Arc at 48h post-ECS and determined the role of de-novo methylation in that process. We initially measured expression of DNA methyltransferases (Dnmt1 and Dnmt3a) and Arc 1, 4, 8, 16, 24, and 48h after a single ECS. Arc expression increased approximately 10-fold at 1 and 4h after ECS, and subsequently decreased below sham levels. Four hours after ECS we also observed a significant increase in Dnmt3a expression, which was attenuated in a second experiment by the use of DNMT inhibitor decitabine (5-aza-2-deoxycytidine). We then investigated Arc gene expression and methylation changes at 48h post-ECS and we found a slightly reduced Arc expression in ECS-treated rats as compared to sham. In animals that received decitabine we observed a significant decrease in Dnmt3a expression and an increase of Arc expression in both ECS and sham groups. The same tendency for reduced Arc expression after ECS, as compared to sham was observed despite the blocking of DNA methylation with decitabine. The DNA methylation as measured by pyrosequencing is decreased 48h post-ECS both in the promoter and intragenic regions as a response to ECS regardless of the treatment with decitabine. Overall the results suggest that DNA methylation is involved in regulating Arc expression but is not the causal mechanism responsible for reducing Arc expression after ECS. We speculate that the decrease is caused by ECS-induced HDAC2 upregulation and decreased H3 acetylation at the Arc promoter. PMID- 26141856 TI - 2001 Presidential Address. PMID- 26141857 TI - Commentary on Genetic Counseling-A Profession in Search of Itself. PMID- 26141859 TI - Genetic Library. PMID- 26141858 TI - Determining Complex Genetic Risks by Computer. AB - Genetic risk analysis is a frequent and important responsibility for genetic counselors. Computer-based methods of determining risk are available but not generally used. In this paper, we present a computer-based likelihood approach for performing risk calculations (including Bayesian analysis), and the implementation of this approach using the CYRILLIC and LINKAGE computer packages. Several concrete examples are given, and caveats (which can also be applied to other programs for risk calculation) are discussed. PMID- 26141860 TI - Microenvironment-Modulated Metastatic CD133+/CXCR4+/EpCAM- Lung Cancer-Initiating Cells Sustain Tumor Dissemination and Correlate with Poor Prognosis. AB - Metastasis is the main reason for lung cancer-related mortality, but little is known about specific determinants of successful dissemination from primary tumors and metastasis initiation. Here, we show that CD133(+)/CXCR4(+) cancer-initiating cells (CIC) directly isolated from patient-derived xenografts (PDX) of non-small cell lung cancer are endowed with superior ability to seed and initiate metastasis at distant organs. We additionally report that CXCR4 inhibition successfully prevents the increase of cisplatin-resistant CD133(+)/CXCR4(+) cells in residual tumors and their metastatization. Immunophenotypic analysis of lung tumor cells intravenously injected or spontaneously disseminated to murine lungs demonstrated the survival advantage and increased colonization ability of a specific subset of CD133(+)/CXCR4(+) with reduced expression of epithelial cell adhesion molecule (EpCAM(-)), which also shows the greatest in vitro invasive potential. We next prove that recovered disseminated cells from lungs of PDX bearing mice enriched for CD133(+)/CXCR4(+)/EpCAM(-) CICs are highly tumorigenic and metastatic. Importantly, microenvironment stimuli eliciting epithelial-to mesenchymal transition, including signals from cancer-associated fibroblasts, are able to increase the dissemination potential of lung cancer cells through the generation of the CD133(+)/CXCR4(+)/EpCAM(-) subset. These findings also have correlates in patient samples where disseminating CICs are enriched in metastatic lymph nodes (20-fold, P = 0.006) and their detection in primary tumors is correlated with poor clinical outcome (disease-free survival: P = 0.03; overall survival: P = 0.05). Overall, these results highlight the importance of specific cellular subsets in the metastatic process, the need for in-depth characterization of disseminating tumor cells, and the potential of therapeutic strategies targeting both primary tumor and tumor-microenvironment interactions. PMID- 26141861 TI - Epigenetic Activation of TWIST1 by MTDH Promotes Cancer Stem-like Cell Traits in Breast Cancer. AB - Cancer stem-like cells (CSC) are a cell subpopulation that can reinitiate tumors, resist chemotherapy, and give rise to metastases. Metadherin (MTDH) contributes widely to tumor growth, drug resistance, relapse, and metastasis, but its molecular mechanisms of action are not well understood. Here, we report that MTDH drives CSC expansion by promoting the expression of TWIST1, a transcription factor critical for cancer cell stemness and metastasis. MTDH activates TWIST1 expression indirectly by facilitating histone H3 acetylation on the TWIST1 promoter, a process mediated by the histone acetyltransferase CBP. Mechanistic investigations showed that MTDH interacts with CBP and prevents its ubiquitin mediated degradation, licensing its transcriptional activation of TWIST1. In clinical specimens of breast cancer, MTDH expression correlates positively with TWIST1 expression and CSC abundance. Overall, our work revealed that MTDH promotes CSC accumulation and breast tumorigenicity by regulating TWIST1, deepening the understanding of MTDH function in cancer. PMID- 26141862 TI - Depleting MET-Expressing Tumor Cells by ADCC Provides a Therapeutic Advantage over Inhibiting HGF/MET Signaling. AB - Hepatocyte growth factor (HGF) and its receptor MET represent validated targets for cancer therapy. However, HGF/MET inhibitors being explored as cancer therapeutics exhibit cytostatic activity rather than cytotoxic activity, which would be more desired. In this study, we engineered an antagonistic anti-MET antibody that, in addition to blocking HGF/MET signaling, also kills MET overexpressing cancer cells by antibody-dependent cellular cytotoxicity (ADCC). As a control reagent, we engineered the same antibody in an ADCC-inactive form that is similarly capable of blocking HGF/MET activity, but in the absence of any effector function. In comparing these two antibodies in multiple mouse models of cancer, including HGF-dependent and -independent tumor xenografts, we determined that the ADCC-enhanced antibody was more efficacious than the ADCC-inactive antibody. In orthotopic mammary carcinoma models, ADCC enhancement was crucial to deplete circulating tumor cells and to suppress metastases. Prompted by these results, we optimized the ADCC-enhanced molecule for clinical development, generating an antibody (ARGX-111) with improved pharmacologic properties. ARGX 111 competed with HGF for MET binding, inhibiting ligand-dependent MET activity, downregulated cell surface expression of MET, curbing HGF-independent MET activity, and engaged natural killer cells to kill MET-expressing cancer cells, displaying MET-specific cytotoxic activity. ADCC assays confirmed the cytotoxic effects of ARGX-111 in multiple human cancer cell lines and patient-derived primary tumor specimens, including MET-expressing cancer stem-like cells. Together, our results show how ADCC provides a therapeutic advantage over conventional HGF/MET signaling blockade and generates proof-of-concept for ARGX 111 clinical testing in MET-positive oncologic malignancies. PMID- 26141863 TI - CHK1 Inhibition Synergizes with Gemcitabine Initially by Destabilizing the DNA Replication Apparatus. AB - Combining cell-cycle checkpoint kinase inhibitors with the DNA-damaging chemotherapeutic agent gemcitabine offers clinical appeal, with a mechanistic rationale based chiefly on abrogation of gemcitabine-induced G2-M checkpoint activation. However, evidence supporting this mechanistic rationale from chemosensitization studies has not been consistent. Here we report a systematic definition of how pancreatic cancer cells harboring mutant p53 respond to this combination therapy, by combining mathematical models with large-scale quantitative biologic analyses of single cells and cell populations. Notably, we uncovered a dynamic range of mechanistic effects at different ratios of gemcitabine and CHK1 inhibitors. Remarkably, effective synergy was attained even where cells exhibited an apparently functional G2-M surveillance mechanism, as exemplified by a lack of both overt premature CDK1 activation and S-phase mitotic entry. Consistent with these findings, S-G2 duration was extended in treated cells, leading to a definable set of lineage-dependent catastrophic fates. At synergistic drug concentrations, global replication stress was a distinct indicator of chemosensitization as characterized molecularly by an accumulation of S-phase cells with high levels of hyperphosphorylated RPA-loaded single stranded DNA. In a fraction of these cells, persistent genomic damage was observed, including chromosomal fragmentation with a loss of centromeric regions that prevented proper kinetochore-microtubule attachment. Together, our results suggested a "foot-in-the-door" mechanism for drug synergy where cells were destroyed not by frank G2-M phase abrogation but rather by initiating a cumulative genotoxicity that deregulated DNA synthesis. PMID- 26141864 TI - Children hospitalized due to acute otitis media: how does this condition differ from acute mastoiditis? AB - OBJECTIVES: To evaluate the clinical picture and microbiological findings of children hospitalized due to acute otitis media and to analyze how it differs from acute mastoiditis. METHODS: A retrospective review of the medical records of all children (0-16 years) hospitalized due to acute otitis media in the Department of Otorhinolaryngology at the Helsinki University Hospital, between 2003 and 2012. Comparison with previously published data of children with acute mastoiditis (n=56) from the same institute and period of time. RESULTS: The most common pathogens in the children hospitalized due to acute otitis media (n=44) were Streptococcus pneumoniae (18%), Pseudomonas aeruginosa (16%), Streptococcus pyogenes (14%), and Staphylococcus aureus (14%). One of the most common pathogens of out-patient acute otitis media, Haemophilus influenzae, was absent. Otorrhea was common in infections caused by S. pyogenes and otorrhea via tympanostomy tube in infections caused by P. aeruginosa. In children under 2 years-of-age, the most common pathogens were S. pneumoniae (43%), Moraxella catarrhalis (14%), and S. aureus (7%). S. pyogenes and P. aeruginosa were only found in children over 2 years-of-age. Previous health problems, bilateral infections, and facial nerve paresis were more common in children hospitalized due to acute otitis media, compared with acute mastoiditis, but they also demonstrated lower CRP values and shorter duration of hospital stay. The number of performed tympanostomies and mastoidectomies was also comparatively smaller in the children hospitalized due to acute otitis media. S. aureus was more common and S. pneumoniae, especially its resistant strains, was less common in the children hospitalized due to acute otitis media than acute mastoiditis. CONCLUSIONS: Acute otitis media requiring hospitalization and acute mastoiditis compose a continuum of complicated acute otitis media that differs from common out-patient acute otitis media. The bacteriology of children hospitalized due to acute otitis media resembled more the bacteriology of acute mastoiditis than that of out-patient acute otitis media. The children hospitalized due to acute otitis media needed less surgical treatment and a shorter hospitalization than those hospitalized due to acute mastoiditis. PMID- 26141865 TI - Excessive daytime sleepiness and falls among older men and women: cross-sectional examination of a population-based sample. AB - BACKGROUND: Excessive daytime sleepiness (EDS) has been associated with an increased risk for falls among clinical samples of older adults. However, there is little detailed information among population-representative samples. The current study aimed to assess the relationship between EDS and falls among a cohort of population-based older adults. METHODS: This study assessed 367 women aged 60-93 years (median 72, interquartile range 65-79) and 451 men aged 60-92 years (median 73, interquartile range 66-80) who participated in the Geelong Osteoporosis Study between the years 2001 and 2008. Falls during the prior year were documented via self-report, and for men, falls risk score was obtained using an Elderly Fall Screening Test (EFST). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS), and scores of >= 10 indicated EDS. Differences among those with and without EDS in regard to falls were tested using logistic regression models. RESULTS: Among women, 50 (13.6%) individuals reported EDS. Women with EDS were more likely to report a fall, and were more likely to report the fall occurring outside. EDS was similarly associated with an increased risk of a fall following adjustment for use of a walking aid, cases of nocturia and antidepressant medication use (adjusted OR = 2.54, 95% CI 1.24-5.21). Multivariate modelling revealed antidepressant use (current) as an effect modifier (p < .001 for the interaction term). After stratifying the data by antidepressant medication use, the association between EDS and falls was sustained following adjustment for nocturia among antidepressant non-users (adjusted OR = 2.63, 95% CI 1.31-5.30). Among men, 72 (16.0%) individuals reported EDS. No differences were detected for men with and without EDS in regard to reported falls, and a trend towards significance was noted between EDS and a high falls risk as assessed by the EFST (p = 0.06), however, age explained this relationship (age adjusted OR = 2.20, 95% CI 1.03-1.10). CONCLUSIONS: For women, EDS is independently associated with at least one fall during the previous year, and this is more likely to occur whilst located outside. Amelioration of EDS may assist in improving functional outcomes among these individuals by reducing the risk for falls. PMID- 26141866 TI - Metabolomics and Natural-Products Strategies to Study Chemical Ecology in Nematodes. AB - This review provides an overview of two complementary approaches to identify biologically active compounds for studies in chemical ecology. The first is activity-guided fractionation and the second is metabolomics, particularly focusing on a new liquid chromatography-mass spectrometry-based method called isotopic ratio outlier analysis. To illustrate examples using these approaches, we review recent experiments using Caenorhabditis elegans and related free-living nematodes. PMID- 26141867 TI - Living in a Turbulent World-A New Conceptual Framework for the Interactions of Fish and Eddies. AB - The natural habitats of fishes are characterized by movements of water driven by a multitude of physical processes of either natural or human origin. The resultant unsteadiness is exacerbated when flow interacts with surfaces, such as the bottom and banks, and protruding objects, such as corals, boulders, and woody debris. There is growing interest in the impacts on performance and behavior of fishes swimming in "turbulent flows". The ability of fishes to stabilize their postures and their swimming trajectories is thought to be important in determining species' distributions and densities, and hence the resultant assemblages in various habitats. A theoretical framework is proposed to quantify the interactions of fish and flows. Dimensionless parameters are derived based on a physical description of the flow structures and different regimes are predicted describing fishes' responses to a wide range of physical perturbations. We found the ratio of eddy size to fish size, the "momentum ratio" (ratio between momentum of the eddy and the momentum of the fish), as well as the time of interaction between eddy and fish to be especially important in determining thresholds for the fish's posture and trajectory. PMID- 26141868 TI - Similarity of Crocodilian and Avian Lungs Indicates Unidirectional Flow Is Ancestral for Archosaurs. AB - Patterns of airflow and pulmonary anatomy were studied in the American alligator (Alligator mississippiensis), the black caiman (Melanosuchus niger), the spectacled caiman (Caiman crocodilus), the dwarf crocodile (Osteolaemus tetraspis), the saltwater crocodile (Crocodylus porosus), the Nile crocodile (Crocodylus niloticus), and Morelet's crocodile (Crocodylus moreletii). In addition, anatomy was studied in the Orinoco crocodile (Crocodylus intermedius). Airflow was measured using heated thermistor flow meters and visualized by endoscopy during insufflation of aerosolized propolene glycol and glycerol. Computed tomography and gross dissection were used to visualize the anatomy. In all species studied a bird-like pattern of unidirectional flow was present, in which air flowed caudad in the cervical ventral bronchus and its branches during both lung inflation and deflation and craniad in dorsobronchi and their branches. Tubular pathways connected the secondary bronchi to each other and allowed air to flow from the dorsobronchi into the ventrobronchi. No evidence for anatomical valves was found, suggesting that aerodynamic valves cause the unidirectional flow. In vivo data from the American alligator showed that unidirectional flow is present during periods of breath-holding (apnea) and is powered by the beating heart, suggesting that this pattern of flow harnesses the heart as a pump for air. Unidirectional flow may also facilitate washout of stale gases from the lung, reducing the cost of breathing, respiratory evaporative water loss, heat loss through the heat of vaporization, and facilitating crypsis. The similarity in structure and function of the bird lung with pulmonary anatomy of this broad range of crocodilian species indicates that a similar morphology and pattern of unidirectional flow were present in the lungs of the common ancestor of crocodilians and birds. These data suggest a paradigm shift is needed in our understanding of the evolution of this character. Although conventional wisdom is that unidirectional flow is important for the high activity and basal metabolic rates for which birds are renowned, the widespread occurrence of this pattern of flow in crocodilians indicates otherwise. Furthermore, these results show that air sacs are not requisite for unidirectional flow, and therefore raise questions about the function of avian air sacs. PMID- 26141869 TI - Interleukin 17A plays a role in lipopolysaccharide/D-galactosamine-induced fulminant hepatic injury in mice. AB - BACKGROUND: Lipopolysaccharide/d-galactosamine (LPS/GalN)-induced hepatic injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor alpha (TNF-alpha) plays a pivotal role. Moreover, it was reported from our laboratory that interleukin (IL) 17A enhanced production of TNF-alpha by the Kupffer cell. OBJECTIVE: The purpose of this study was to determine the role of IL-17A in LPS/GalN-induced hepatic injury in mice. METHODS: LPS/GalN was injected into three mouse models: wild-type (WT) mice, IL-17A knockout (KO) mice, or IL 17A KO mice treated with recombinant mouse (rm) IL-17A homodimer (KO + rmIL-17A). Survival was assessed for 24 h after LPS/GalN injection, and histopathologic findings were evaluated at various time points after LPS/GalN injection for neutrophil and apoptosis markers. After LPS/GalN injection, expression of the inflammatory mediators TNF-alpha, IL-6, monocyte chemotactic protein 1, IL-17A, high-mobility group box 1, and soluble intercellular adhesion molecule 1 was assessed in serum by enzyme-linked immunosorbent assay. RESULTS: Survival was higher in KO mice compared with WT mice after LPS/GalN injection. However, in KO + rmIL-17A mice, mortality was not significantly different compared to the other groups. Neutrophil infiltration and apoptosis were significantly greater in WT mice than KO mice. Furthermore, serum alanine aminotransferase, serum TNF-alpha, monocyte chemotactic protein 1, IL-17A, high-mobility group box 1, and soluble intercellular adhesion molecule 1 levels were also significantly greater in WT mice than KO mice. In KO + rmIL-17A mice, these levels were similar to those in WT mice. CONCLUSIONS: IL-17A is a key regulator in hepatic injury caused by neutrophil-induced inflammatory responses after LPS/GalN injection. PMID- 26141870 TI - The use of negative pressure wound therapy in severe open lower extremity fractures: identifying the association between length of therapy and surgical outcomes. AB - BACKGROUND: Negative pressure wound therapy (NPWT) is a widely accepted method of temporary coverage for complex lower extremity wounds before definitive reconstruction. However, the precise role of NPWT in the perioperative management of patients with complicated lower extremity injuries remains unclear. In this study, we examine the effect of NPWT on flap complications and overall outcomes based on timing of soft-tissue reconstruction relative to initial injury and implementation of NPWT. METHODS: We retrospectively reviewed the medical records of 32 consecutive patients presenting to a single institution receiving lower extremity reconstruction after Gustilo class IIIB or IIIC open tibial fractures over a 5-y period. Length of hospitalization, number of surgical procedures, flap failure, infection, and nonunion were parameters of interest in this study. RESULTS: The incidence of complications in patients treated with NPWT was lower compared with patients who underwent wet-to-dry dressing changes, regardless of when surgery was performed. The highest rate of complications was observed in patients operated on >6 wk after injury and who received wet-to-dry dressing changes wound care. By comparison, those who underwent surgery within 1 wk of injury and who were bridged with NPWT had the lowest rate of complications. CONCLUSIONS: The use of NPWT therapy in the perioperative management of patients with open lower extremity fractures reduces complication rates associated with limb salvage surgery. Our results suggest that NPWT can be used as a temporizing measure to optimize patients before flap surgery, effectively lengthening the window of opportunity for definitive reconstruction. PMID- 26141871 TI - Solid cancer increase among Chernobyl liquidators: alternative explanation. PMID- 26141872 TI - The effects of temperature on decomposition and allelopathic phytotoxicity of boneseed litter. AB - Decomposition of plant litter is a fundamental process in ecosystem function, carbon and nutrient cycling and, by extension, climate change. This study aimed to investigate the role of temperature on the decomposition of water soluble phenolics (WSP), carbon and soil nutrients in conjunction with the phytotoxicity dynamics of Chrysanthemoides monilifera subsp. monilifera (boneseed) litter. Treatments consisted of three factors including decomposition materials (litter alone, litter with soil and soil alone), decomposition periods and temperatures (5-15, 15-25 and 25-35 degrees C (night/day)). Leachates were collected on 0, 5, 10, 20, 40 and 60th days to analyse physico-chemical parameters and phytotoxicity. Water soluble phenolics and dissolved organic carbon (DOC) increased with increasing temperature while nutrients like SO4(-2) and NO3(-1) decreased. Speed of germination, hypocotyl and radical length and weight of Lactuca sativa exposed to leachates were decreased with increasing decomposition temperature. All treatment components had significant effects on these parameters. There had a strong correlation between DOC and WSP, and WSP content of the leachates with radical length of test species. This study identified complex interactivity among temperature, WSP, DOC and soil nutrient dynamics of litter occupied soil and that these factors work together to influence phytotoxicity. PMID- 26141873 TI - Advanced treatment of biologically pretreated coal gasification wastewater by a novel heterogeneous Fenton oxidation process. AB - Sewage sludge from a biological wastewater treatment plant was converted into sewage sludge based activated carbon (SBAC) with ZnCl2 as activation agent, which was used as a support for ferric oxides to form a catalyst (FeOx/SBAC) by a simple impregnation method. The new material was then used to improve the performance of Fenton oxidation of real biologically pretreated coal gasification wastewater (CGW). The results indicated that the prepared FeOx/SBAC significantly enhanced the pollutant removal performance in the Fenton process, so that the treated wastewater was more biodegradable and less toxic. The best performance was obtained over a wide pH range from 2 to 7, temperature 30 degrees C, 15 mg/L of H2O2 and 1g/L of catalyst, and the treated effluent concentrations of COD, total phenols, BOD5 and TOC all met the discharge limits in China. Meanwhile, on the basis of significant inhibition by a radical scavenger in the heterogeneous Fenton process as well as the evolution of FT-IR spectra of pollutant-saturated FeOx/BAC with and without H2O2, it was deduced that the catalytic activity was responsible for generating hydroxyl radicals, and a possible reaction pathway and interface mechanism were proposed. Moreover, FeOx/SBAC showed superior stability over five successive oxidation runs. Thus, heterogeneous Fenton oxidation of biologically pretreated CGW by FeOx/SBAC, with the advantages of being economical, efficient and sustainable, holds promise for engineering application. PMID- 26141874 TI - Enhancement of Rhodobacter sphaeroides growth and carotenoid production through biostimulation. AB - Bacillus thuringiensis/cereus L2 was added as a biostimulant to enhance the biomass accumulation and carotenoid yield of Rhodobacter sphaeroides using wastewater as the culturing medium. Results showed that biostimulation could significantly enhance the R. sphaeroides biomass production and carotenoid yield. The optimal biostimulant proportion was 40 MUL (about 6.4*10(5) CFU). Through the use of biostimulation, chemical oxygen demand removal, R. sphaeroides biomass production, carotenoid concentration, and carotenoid yield were improved by 178%, 67%, 214%, and 70%, respectively. Theoretical analysis revealed that there were two possible reasons for such increases. One was that biostimulation enhanced the R. sphaeroides wastewater treatment efficiency. The other was that biostimulation significantly decreased the peroxidase activity in R. sphaeroides. The results showed that the highest peroxidase activity dropped by 87% and the induction ratio of the RSP_3419 gene was 3.1 with the addition of biostimulant. The enhanced carotenoid yield in R. sphaeroides could thus be explained by a decrease in peroxidase activity. PMID- 26141875 TI - Impact of ozone assisted ultrasonication pre-treatment on anaerobic digestibility of sewage sludge. AB - Impact of ultrasonication (ULS) and ultrasonication-ozonation (ULS-Ozone) pre treatment on the anaerobic digestibility of sewage sludge was investigated with semi-continuous anaerobic reactors at solid retention time (SRT) of 10 and 20 days. The control, ULS and ULS-Ozone reactors produced 256, 309 and 348 mL biogas/g CODfed and the volatile solid (VS) removals were 35.6%, 38.3% and 42.1%, respectively at SRT of 10 days. At SRT of 20 days, the biogas yields reached 313, 337 and 393 mL biogas/g CODfed and the VS removal rates were 37.3%, 40.9% and 45.3% in the control, ULS and ULS-Ozone reactors, respectively. ULS-Ozone pre treatment increased the residual organic amount in the digested sludge. These soluble residual organics were found to contain macromolecules with molecular weights (MW) larger than 500 kDa and smaller polymeric products with MW around 19.4 and 7.7 kDa. These compounds were further characterized to be humic acid like substances with fluorescent spectroscopy analysis. PMID- 26141876 TI - Spectrophotometric analyses of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in water. AB - A simple and accurate spectrophotometric method for on-site analysis of royal demolition explosive (RDX) in water samples was developed based on the Berthelot reaction. The sensitivity and accuracy of an existing spectrophotometric method was improved by: replacing toxic chemicals with more stable and safer reagents; optimizing the reagent dose and reaction time; improving color stability; and eliminating the interference from inorganic nitrogen compounds in water samples. Cation and anion exchange resin cartridges were developed and used for sample pretreatment to eliminate the effect of ammonia and nitrate on RDX analyses. The detection limit of the method was determined to be 100 MUg/L. The method was used successfully for analysis of RDX in untreated industrial wastewater samples. It can be used for on-site monitoring of RDX in wastewater for early detection of chemical spills and failure of wastewater treatment systems. PMID- 26141877 TI - Effects of cowpea (Vigna unguiculata) root mucilage on microbial community response and capacity for phenanthrene remediation. AB - Biodegradation of polycyclic aromatic hydrocarbons (PAHs) is normally limited by their low solubility and poor bioavailability. Prior research suggests that biosurfactants are synthesized as intermediates during the production of mucilage at the root tip. To date the effects of mucilage on PAH degradation and microbial community response have not been directly examined. To address this question, our research compared 3 cowpea breeding lines (Vigna unguiculata) that differed in mucilage production for their effects on phenanthrene (PHE) degradation in soil. The High Performance Liquid Chromatography results indicated that the highest PHE degradation rate was achieved in soils planted with mucilage producing cowpea line C1, inoculated with Bradyrhizobium, leading to 91.6% PHE disappearance in 5 weeks. In root printing tests, strings treated with mucilage and bacteria produced larger clearing zones than those produced on mucilage treated strings with no bacteria or bacteria inoculated strings. Experiments with 14C-PHE and purified mucilage in soil slurry confirmed that the root mucilage significantly enhanced PHE mineralization (82.7%), which is 12% more than the control treatment without mucilage. The profiles of the PHE degraders generated by Denaturing gradient gel electrophoresis suggested that cowpea C1, producing a high amount of root mucilage, selectively enriched the PHE degrading bacteria population in rhizosphere. These findings indicate that root mucilage may play a significant role in enhancing PHE degradation and suggests that differences in mucilage production may be an important criterion for selection of the best plant species for use in phytoremediation of PAH contaminated soils. PMID- 26141878 TI - The roles of active species in photo-decomposition of organic compounds by microwave powered electrodeless discharge lamps. AB - Knowledge of the effective radiation spectrum irradiating substrates from microwave powered electrodeless discharge lamps (MEDLs), and the active species that directly oxidize substrates in the photolytic process, is fragmentary and unclear. In this work, we conducted a comparative study using MEDLs made with quartz envelopes (MEDL-quartz) and with borosilicate Pyrex envelopes (MEDL-Pyrex) targeting the degradation of Rhodamine B (RhB) via radical-extinguishing tests. We found that UVC/UVB radiation is essential to generate *OH and H2O2 in the MEDL quartz system. The degradation of RhB mostly originates from *OH species, which account for a contribution of 53.8%, while the remaining contribution is attributed to oxidation by H2O2 and direct photolysis. This degradation is influenced by several parameters. Acidic and neutral pHs, but not extreme alkaline pH, benefit the degradation. To ensure a high intensity of UVC/UVB, the optimum ratio of the MEDL volume to the aqueous solution volume (VL/VS) is 0.4. Concentrations of 0.15-0.20 mmol/L of RhB are suitable to obtain an effective quantum absorbance in the MEDL-quartz system, showing a high decomposition rate of 5.6*10(-3) (mmol/L) min(-1). Moreover, two other substrates, Reactive Brilliant Red X-3B and Safranine T, were tested and found to be efficiently degraded in the MEDL-quartz system. PMID- 26141879 TI - Emission of oxygenated volatile organic compounds (OVOCs) during the aerobic decomposition of orange wastes. AB - Oxygenated volatile organic compounds (OVOCs) emitted from orange wastes during aerobic decomposition were investigated in a laboratory-controlled incubator for a period of two months. Emission of total OVOCs (TOVOCs) from orange wastes reached 1714 mg/dry kg (330 mg/wet kg). Ethanol, methanol, ethyl acetate, methyl acetate, 2-butanone and acetaldehyde were the most abundant OVOC species with shares of 26.9%, 24.8%, 20.3%, 13.9%, 2.8% and 2.5%, respectively, in the TOVOCs released. The emission fluxes of the above top five OVOCs were quite trivial in the beginning but increased sharply to form one "peak emission window" with maximums at days 1-8 until leveling off after 10 days. This type of "peak emission window" was synchronized with the CO2 fluxes and incubation temperature of the orange wastes, indicating that released OVOCs were mainly derived from secondary metabolites of orange substrates through biotic processes rather than abiotic processes or primary volatilization of the inherent pool in oranges. Acetaldehyde instead had emission fluxes decreasing sharply from its initial maximum to nearly zero in about four days, suggesting that it was inherent rather than secondarily formed. For TOVOCs or all OVOC species except 2-butanone and acetone, over 80% of their emissions occurred during the first week, implying that organic wastes might give off a considerable amount of OVOCs during the early disposal period under aerobic conditions. PMID- 26141880 TI - The effect of continuous Ni(II) exposure on the organic degradation and soluble microbial product (SMP) formation in two-phase anaerobic reactor. AB - A two-phase anaerobic reactor fed with glucose substrate (3 g chemical oxygen demand (COD)/L) was used to investigate the effects of toxic metals on the degradation of organics and the soluble microbial product (SMP) formation. Low concentrations of Ni(II) (5 and 10 mg/L) promoted the acid phase, whereas high concentrations (15, 20, and 25 mg/L) exhibited an inhibitory effect on, but did not alter the fermentative method, which mainly involved the fermentation of propionic acid. The methanogenic microorganism exhibited a strong capability adapting constantly increased Ni(II) levels. The acid phase was an accumulation stage of SMP. In the absence of Ni(II), the high-molecular-weight material in the effluent SMP mainly contained polysaccharide, tryptophan, and casein. Methanogens metabolized most of the polysaccharide, the whole tryptophan content, and part of the casein, leading to the presence of humic acid and protein in effluent. After Ni(II) dosage, the protein and polysaccharide of the acid phase increased, and tryptophan changed, while casein remained stable. More protein than polysaccharide was produced, suggesting the prominent function of protein when addressing the negative effect of toxic metals. The analysis of DNA confirmed the change of bacterial activity. PMID- 26141881 TI - Vehicular volatile organic compounds losses due to refueling and diurnal process in China: 2010-2050. AB - Volatile organic compounds (VOCs) are crucial to control air pollution in major Chinese cities since VOCs are the dominant factor influencing ambient ozone level, and also an important precursor of secondary organic aerosols. Vehicular evaporative emissions have become a major and growing source of VOC emissions in China. This study consists of lab tests, technology evaluation, emissions modeling, policy projections and cost-benefit analysis to draw a roadmap for China for controlling vehicular evaporative emissions. The analysis suggests that evaporative VOC emissions from China's light-duty gasoline vehicles were approximately 185,000 ton in 2010 and would peak at 1,200,000 ton in 2040 without control. The current control strategy implemented in China, as shown in business as usual (BAU) scenario, will barely reduce the long-term growth in emissions. Even if Stage II gasoline station vapor control policies were extended national wide (BAU+extended Stage II), there would still be over 400,000 ton fuel loss in 2050. In contrast, the implementation of on-board refueling vapor recovery (ORVR) on new cars could reduce 97.5% of evaporative VOCs by 2050 (BAU+ORVR/BAU+delayed ORVR). According to the results, a combined Stage II and ORVR program is a comprehensive solution that provides both short-term and long-term benefits. The net cost to achieve the optimal total evaporative VOC control is approximately 62 billion CNY in 2025 and 149 billion CNY in 2050. PMID- 26141882 TI - Activated carbon coated palygorskite as adsorbent by activation and its adsorption for methylene blue. AB - An activation process for developing the surface and porous structure of palygorskite/carbon (PG/C) nanocomposite using ZnCl2 as activating agent was investigated. The obtained activated PG/C was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (SEM), and Brunauer-Emmett-Teller analysis (BET) techniques. The effects of activation conditions were examined, including activation temperature and impregnation ratio. With increased temperature and impregnation ratio, the collapse of the palygorskite crystal structure was found to accelerate and the carbon coated on the surface underwent further carbonization. XRD and SEM data confirmed that the palygorskite structure was destroyed and the carbon structure was developed during activation. The presence of the characteristic absorption peaks of CC and C-H vibrations in the FTIR spectra suggested the occurrence of aromatization. The BET surface area improved by more than 11-fold (1201 m2/g for activated PG/C vs. 106 m2/g for PG/C) after activation, and the material appeared to be mainly microporous. The maximum adsorption capacity of methylene blue onto the activated PG/C reached 351 mg/g. The activated PG/C demonstrated better compressive strength than activated carbon without palygorskite clay. PMID- 26141883 TI - Highly effective removal of Methylene Blue using functionalized attapulgite via hydrothermal process. AB - Attapulgite (APT) has been frequently used for the adsorptive removal of dyes from aqueous solution owing to its unique one-dimensional nanoscale structure and low-cost, abundant, eco-friendly advantages. In this work, APT was functionalized under mild hydrothermal condition using chloroacetic acid (CA) with COOH functional groups to improve its adsorption properties. The effect of hydrothermal modification on the microstructure and physicochemical features of APT was investigated by Fourier transform infrared spectroscopy, X-ray diffraction and Field-emission scanning electron microscopy analyses. The effects of hydrothermal reaction parameters on the adsorption properties of modified APT were intensively investigated. It was revealed that the rearrangement of crystal structure and the surface functionalization of APT with COOH groups cause the surprising increase of adsorption capability for Methylene Blue (MB). The removal ratio of raw APT for MB is only 59.52%, while modified APT could almost completely remove MB in the 200 mg/L of MB solution with a removal ratio of 99.8%. The adsorption kinetics fitted pseudo second-order kinetic model, and the adsorption isotherm could be described with Langmuir isotherm model very well. The hydrogen-bonding interaction, electrostatic attraction and chemical association are the main driving force for the adsorption process. PMID- 26141884 TI - Formation and speciation of disinfection byproducts during chlor(am)ination of aquarium seawater. AB - The chemistry associated with the disinfection of aquarium seawater is more complicated than that of freshwater, therefore limited information is available on the formation and speciation of disinfection byproducts (DBPs) in marine aquaria. In this study, the effects of organic precursors, bromide (Br-) and pre ozonation on the formation and speciation of several typical classes of DBPs, including trihalomethanes (THM4), haloacetic acids (HAAs), iodinated trihalomethanes (I-THMs), and haloacetamides (HAcAms), were investigated during the chlorination/chloramination of aquarium seawater. Results indicate that with an increase in dissolved organic carbon concentration from 4.5 to 9.4 mg/L, the concentrations of THM4 and HAAs increased by 3.2-7.8 times under chlorination and by 1.1-2.3 times under chloramination. An increase in Br- concentration from 3 to 68 mg/L generally enhanced the formation of THM4, I-THMs and HAcAms and increased the bromine substitution factors of all studied DBPs as well, whereas it impacted insignificantly on the yield of HAAs. Pre-ozonation with 1 mg/L O3 dose substantially reduced the formation of all studied DBPs in the subsequent chlorination and I-THMs in the subsequent chloramination. Because chloramination produces much lower amounts of DBPs than chlorination, it tends to be more suitable for disinfection of aquarium seawater. PMID- 26141885 TI - Economic analysis of atmospheric mercury emission control for coal-fired power plants in China. AB - Coal combustion and mercury pollution are closely linked, and this relationship is particularly relevant in China, the world's largest coal consumer. This paper begins with a summary of recent China-specific studies on mercury removal by air pollution control technologies and then provides an economic analysis of mercury abatement from these emission control technologies at coal-fired power plants in China. This includes a cost-effectiveness analysis at the enterprise and sector level in China using 2010 as a baseline and projecting out to 2020 and 2030. Of the control technologies evaluated, the most cost-effective is a fabric filter installed upstream of the wet flue gas desulfurization system (FF+WFGD). Halogen injection (HI) is also a cost-effective mercury-specific control strategy, although it has not yet reached commercial maturity. The sector-level analysis shows that 193 tons of mercury was removed in 2010 in China's coal-fired power sector, with annualized mercury emission control costs of 2.7 billion Chinese Yuan. Under a projected 2030 Emission Control (EC) scenario with stringent mercury limits compared to Business As Usual (BAU) scenario, the increase of selective catalytic reduction systems (SCR) and the use of HI could contribute to 39 tons of mercury removal at a cost of 3.8 billion CNY. The economic analysis presented in this paper offers insights on air pollution control technologies and practices for enhancing atmospheric mercury control that can aid decision-making in policy design and private-sector investments. PMID- 26141886 TI - Promoting effect of vanadium on catalytic activity of Pt/Ce-Zr-O diesel oxidation catalysts. AB - A series of Pt-V/Ce-Zr-O diesel oxidation catalysts was prepared using the impregnation method. The catalytic activity and sulfur resistance of Pt-V/Ce-Zr-O were investigated in the presence of simulated diesel exhaust. The effect of vanadium on the structure and redox properties of the catalysts was also investigated using the Brunauer-Emmett-Teller method, X-ray diffraction, H2 temperature-programmed reduction, CO temperature-programmed desorption, X-ray photoelectron spectroscopy, and Energy Dispersive Spectroscopy. Results showed that the Pt particles were well dispersed on the Ce-Zr-O carrier through the vanadium isolation effect, which significantly improved the oxidation activity toward CO and hydrocarbons. An electron-withdrawing phenomenon occurred from V to Pt, resulting in an increase in the metallic nature of platinum, which was beneficial to hydrocarbon molecular activation. PMID- 26141887 TI - Composition and source apportionment of dust fall around a natural lake. AB - The aim of this study was to determine the source apportionment of dust fall around Lake Chini, Malaysia. Samples were collected monthly between December 2012 and March 2013 at seven sampling stations located around Lake Chini. The samples were filtered to separate the dissolved and undissolved solids. The ionic compositions (NO3-, SO4(2-), Cl- and NH4+) were determined using ion chromatography (IC) while major elements (K, Na, Ca and Mg) and trace metals (Zn, Fe, Al, Ni, Mn, Cr, Pb and Cd) were determined using inductively coupled plasma mass spectrometry (ICP-MS). The results showed that the average concentration of total solids around Lake Chini was 93.49+/-16.16 mg/(m2.day). SO4(2-), Na and Zn dominated the dissolved portion of the dust fall. The enrichment factors (EF) revealed that the source of the trace metals and major elements in the rain water was anthropogenic, except for Fe. Hierarchical agglomerative cluster analysis (HACA) classified the seven monitoring stations and 16 variables into five groups and three groups respectively. A coupled receptor model, principal component analysis multiple linear regression (PCA-MLR), revealed that the sources of dust fall in Lake Chini were dominated by agricultural and biomass burning (42%), followed by the earth's crust (28%), sea spray (16%) and a mixture of soil dust and vehicle emissions (14%). PMID- 26141888 TI - Mercury adsorption characteristics of HBr-modified fly ash in an entrained-flow reactor. AB - In this study, the mercury adsorption characteristics of HBr-modified fly ash in an entrained-flow reactor were investigated through thermal decomposition methods. The results show that the mercury adsorption performance of the HBr modified fly ash was enhanced significantly. The mercury species adsorbed by unmodified fly ash were HgCl2, HgS and HgO. The mercury adsorbed by HBr-modified fly ash, in the entrained-flow reactor, existed in two forms, HgBr2 and HgO, and the HBr was the dominant factor promoting oxidation of elemental mercury in the entrained-flow reactor. In the current study, the concentration of HgBr2 and HgO in ash from the fine ash vessel was 4.6 times greater than for ash from the coarse ash vessel. The fine ash had better mercury adsorption performance than coarse ash, which is most likely due to the higher specific surface area and longer residence time. PMID- 26141889 TI - Effects of metal ions on the catalytic degradation of dicofol by cellulase. AB - A new technique whereby cellulase immobilized on aminated silica was applied to catalyze the degradation of dicofol, an organochlorine pesticide. In order to evaluate the performance of free and immobilized cellulase, experiments were carried out to measure the degradation efficiency. The Michaelis constant, Km, of the reaction catalyzed by immobilized cellulase was 9.16 mg/L, and the maximum reaction rate, Vmax, was 0.40 mg/L/min, while that of free cellulase was Km=8.18 mg/L, and Vmax=0.79 mg/L/min, respectively. The kinetic constants of catalytic degradation were calculated to estimate substrate affinity. Considering that metal ions may affect enzyme activity, the effects of different metal ions on the catalytic degradation efficiency were explored. The results showed that the substrate affinity decreased after immobilization. Monovalent metal ions had no effect on the reaction, while divalent metal ions had either positive or inhibitory effects, including activation by Mn2+, reversible competition with Cd2+, and irreversible inhibition by Pb2+. Ca2+ promoted the catalytic degradation of dicofol at low concentrations, but inhibited it at high concentrations. Compared with free cellulase, immobilized cellulase was affected less by metal ions. This work provided a basis for further studies on the co occurrence of endocrine-disrupting chemicals and heavy metal ions in the environment. PMID- 26141890 TI - Photocatalytic decomposition of acrylonitrile with N-F codoped TiO2/SiO2 under simulant solar light irradiation. AB - The solid acid catalyst, N-F codoped TiO2/SiO2 composite oxide was prepared by a sol-gel method using NH4F as nitrogen and fluorine source. The prepared materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), UV-Visible diffuse reflectance spectroscopy (UV-Vis), ammonia adsorption and temperature-programmed desorption (NH3-TPD), in situ Fourier transform infrared spectroscopy (FT-IR) and N2 physical adsorption isotherm. The photocatalytic activity of the catalyst for acrylonitrile degradation was investigated under simulant solar irradiation. The results showed that strong Lewis and Bronsted acid sites appear on the surface of the sample after N-F doping. Systematic investigation showed that the highest photocatalytic activity for acrylonitrile degradation was obtained for samples calcined at 450 degrees C with molar ratio (NH4F to Ti) of 0.8. The degradation ratio of 71.5% was achieved with the prepared catalyst after 6-min irradiation, demonstrating the effectiveness of photocatalytic degradation of acrylonitrile with N-F codoped TiO2/SiO2 composite oxide. The photocatalyst is promising for application under solar light irradiation. Moreover, the intermediates generated after irradiation were verified by gas chromatography-mass spectrometry (GC-MS) analysis and UV-Vis spectroscopy to be simple organic acids with lower toxicity, and the degradation pathway was also proposed for acrylonitrile degradation with the prepared catalyst. PMID- 26141891 TI - Assessment of lead pollution in topsoils of a southern Italy area: Analysis of urban and peri-urban environment. AB - Exposure to lead (Pb) may affect adversely human health. Mapping soil Pb contents is essential to obtain a quantitative estimate of potential risk of Pb contamination. The main aim of this paper was to determine the soil Pb concentrations in the urban and peri-urban area of Cosenza-Rende to map their spatial distribution and assess the probability that soil Pb concentration exceeds a critical threshold that might cause concern for human health. Samples were collected at 149 locations from residual and non-residual topsoil in gardens, parks, flower-beds, and agricultural fields. Fine earth fraction of soil samples was analyzed by X-ray Fluorescence spectrometry. Stochastic images generated by the sequential Gaussian simulation were jointly combined to calculate the probability of exceeding the critical threshold that could be used to delineate the potentially risky areas. Results showed areas in which Pb concentration values were higher to the Italian regulatory values. These polluted areas were quite large and likely, they could create a significant health risk for human beings and vegetation in the near future. The results demonstrated that the proposed approach can be used to study soil contamination to produce geochemical maps, and identify hot-spot areas for soil Pb concentration. PMID- 26141892 TI - Physico-chemical characterization and source tracking of black carbon at a suburban site in Beijing. AB - Particles from ambient air and combustion sources including vehicle emission, coal combustion and biomass burning were collected and chemically pretreated with the purpose of obtaining isolated BC (black carbon) samples. TEM (transmission electron microscopy) results indicate that BC from combustion sources shows various patterns, and airborne BC appears spherical and about 50 nm in diameter with a homogeneous surface and turbostratic structure. The BET (Barrett-Emmett Teller) results suggest that the surface areas of these BC particles fall in the range of 3-23 m2/g, with a total pore volume of 0.03-0.05 cm3/g and a mean pore diameter of 7-53 nm. The nitrogen adsorption-desorption isotherms are indicative of the accumulation mode and uniform pore size. O2-TPO (temperature programmed oxidation) profiles suggest that the airborne BC oxidation could be classified as the oxidation of amorphous carbon, which falls in the range of 406-490 degrees C with peaks at 418, 423 and 475 degrees C, respectively. Generally, the BC characteristics and source analysis suggest that airborne BC most likely comes from diesel vehicle emission at this site. PMID- 26141893 TI - Biological removal of antiandrogenic activity in gray wastewater and coking wastewater by membrane reactor process. AB - A recombinant human androgen receptor yeast assay was applied to investigate the occurrence of antiandrogens as well as the mechanism for their removal during gray wastewater and coking wastewater treatment. The membrane reactor (MBR) system for gray wastewater treatment could remove 88.0% of antiandrogenic activity exerted by weakly polar extracts and 97.3% of that by moderately strong polar extracts, but only 32.5% of that contributed by strong polar extracts. Biodegradation by microorganisms in the MBR contributed to 95.9% of the total removal. After the treatment, the concentration of antiandrogenic activity in the effluent was still 1.05 MUg flutamide equivalence (FEQ)/L, 36.2% of which was due to strong polar extracts. In the anaerobic reactor, anoxic reactor, and membrane reactor system for coking wastewater treatment, the antiandrogenic activity of raw coking wastewater was 78.6 mg FEQ/L, and the effluent of the treatment system had only 0.34 mg FEQ/L. The antiandrogenic activity mainly existed in the medium strong polar and strong polar extracts. Biodegradation by microorganisms contributed to at least 89.2% of the total antiandrogenic activity removal in the system. Biodegradation was the main removal mechanism of antiandrogenic activity in both the wastewater treatment systems. PMID- 26141894 TI - Effect of arsenic on tolerance mechanisms of two plant growth-promoting bacteria used as biological inoculants. AB - Bacterial ability to colonize the rhizosphere of plants in arsenic (As) contaminated soils is highly important for symbiotic and free-living plant growth promoting rhizobacteria (PGPR) used as inoculants, since they can contribute to enhance plant As tolerance and limit metalloid uptake by plants. The aim of this work was to study the effect of As on growth, exopolysaccharide (EPS) production, biofilm formation and motility of two strains used as soybean inoculants, Bradyrhizobium japonicum E109 and Azospirillum brasilense Az39. The metabolism of arsenate (As(V)) and arsenite (As(III)) and their removal and/or possible accumulation were also evaluated. The behavior of both bacteria under As treatment was compared and discussed in relation to their potential for colonizing plant rhizosphere with high content of the metalloid. B. japonicum E109 growth was reduced with As(III) concentration from 10 MUM while A. brasilense Az39 showed a reduction of growth with As(III) from 500 MUM. EPS and biofilm production increased significantly under 25 MUM As(III) for both strains. Moreover, this was more notorious for Azospirillum under 500 MUM As(III), where motility was seriously affected. Both bacterial strains showed a similar ability to reduce As(V). However, Azospirillum was able to oxidize more As(III) (around 53%) than Bradyrhizobium (17%). In addition, both strains accumulated As in cell biomass. The behavior of Azospirillum under As treatments suggests that this strain would be able to colonize efficiently As contaminated soils. In this way, inoculation with A. brasilense Az39 would positively contribute to promoting growth of different plant species under As treatment. PMID- 26141895 TI - Can arbuscular mycorrhiza and fertilizer management reduce phosphorus runoff from paddy fields? AB - Our study sought to assess how much phosphorus (P) runoff from paddy fields could be cut down by fertilizer management and inoculation with arbuscular mycorrhizal fungi. A field experiment was conducted in Lalin River basin, in the northeast China: six nitrogen-phosphorus-potassium fertilizer levels were provided (0, 20%, 40%, 60%, 80%, and 100% of the recommended fertilizer supply), with or without inoculation with Glomus mosseae. The volume and concentrations of particle P (PP) and dissolved P (DP) were measured for each runoff during the rice growing season. It was found that the seasonal P runoff, including DP and PP, under the local fertilization was 3.7 kg/ha, with PP, rather than DP, being the main form of P in runoff water. Additionally, the seasonal P runoff dropped only by 8.9% when fertilization decreased by 20%; rice yields decreased with declining fertilization. We also found that inoculation increased rice yields and decreased P runoff at each fertilizer level and these effects were lower under higher fertilization. Conclusively, while rice yields were guaranteed arbuscular mycorrhizal inoculation and fertilizer management would play a key role in reducing P runoff from paddy fields. PMID- 26141896 TI - Photocatalytic degradation of the diazo dye naphthol blue black in water using MWCNT/Gd,N,S-TiO2 nanocomposites under simulated solar light. AB - A simple sol-gel method was employed to prepare gadolinium, nitrogen and sulphur tridoped titania decorated on oxidised multiwalled carbon nanotubes (MWCNT/Gd,N,S TiO2), using titanium (IV) butoxide and thiourea as titanium and nitrogen and sulphur source, respectively. Samples of varying gadolinium loadings (0.2%, 0.6%, 1.0% and 3.0% Gd3+) relative to titania were prepared to investigate the effect of gadolinium loading and the amounts of carbon nanotubes, nitrogen and sulphur were kept constant for all the samples. Furthermore, the prepared nanocomposites were evaluated for the degradation of naphthol blue black (NBB) in water under simulated solar light irradiation. Higher degradation efficiency (95.7%) was recorded for the MWCNT/Gd,N,S-TiO2 (0.6% Gd) nanocomposites. The higher photocatalytic activity is attributed to the combined effect of improved visible light absorption and charge separation due to the synergistic effect of Gd, MWCNTs, N, S and TiO2. Total organic carbon (TOC) analysis revealed a higher degree of complete mineralisation of naphthol blue black (78.0% TOC removal) which minimises the possible formation of toxic degradation by-products such as the aromatic amines. The MWCNT/Gd,N,S-TiO2 (0.6% Gd) was fairly stable and could be re-used for five times, reaching a maximum degradation efficiency of 91.8% after the five cycles. PMID- 26141897 TI - Syntrophic co-culture of Bacillus subtilis and Klebsiella pneumonia for degradation of kraft lignin discharged from rayon grade pulp industry. AB - In order to search the degradability of kraft lignin, the potential bacterial strains Bacillus subtilis (GU193980) and Klebsiella pneumoniae (GU193981) were isolated, screened and applied in axenic and co-culture conditions. Results revealed that mixed culture showed better decolorization efficiency (80%) and reduction of pollution parameters (COD 73% and BOD 62%) than axenic culture. This indicated syntrophic growth of these two bacteria rather than any antagonistic effect. The HPLC analysis of degraded samples of kraft lignin has shown the reduction in peak area compared to control, suggesting that decrease in color intensity might be largely attributed to the degradation of lignin by isolated bacteria. Further, the GC-MS analysis showed that most of the compounds detected in control were diminished after bacterial treatment. Further, the seed germination test using Phaseolus aureus has supported the detoxification of bacterial decolorized kraft lignin for environmental safety. All these observations have revealed that the developed bacterial co-culture was capable for the effective degradation and decolorization of lignin containing rayon grade pulp mill wastewater for environmental safety. PMID- 26141898 TI - On-line CO, CO2 emissions evaluation and (benzene, toluene, xylene) determination from experimental burn of tropical biomass. AB - Atmospheric pollution and global warming issues are increasingly becoming major environmental concerns. Fire is one of the significant sources of pollutant gases released into the atmosphere; and tropical biomass fires, which are of particular interest in this study, contribute greatly to the global budget of CO and CO2. This pioneer research simulates the natural biomass burning strategy in Malaysia using an experimental burning facility. The investigation was conducted on the emissions (CO2, CO, and Benzene, Toluene, Ethylbenzene, Xylenes (BTEX)) from ten tropical biomass species. The selected species represent the major tropical forests that are frequently subjected to dry forest fire incidents. An experimental burning facility equipped with an on-line gas analyzer was employed to determine the burning emissions. The major emission factors were found to vary among the species, and the specific results were as follows. The moisture content of a particular biomass greatly influenced its emission pattern. The smoke analysis results revealed the existence of BTEX, which were sampled from a combustion chamber by enrichment traps aided with a universal gas sampler. The BTEX were determined by organic solvent extraction followed by GC/MS quantification, the results of which suggested that the biomass burning emission factor contributed significant amounts of benzene, toluene, and m,p-xylene. The modified combustion efficiency (MCE) changed in response to changes in the sample moisture content. Therefore, this study concluded that the emission of some pollutants mainly depends on the burning phase and sample moisture content of the biomass. PMID- 26141899 TI - Effect of petroleum on decomposition of shrub-grass litters in soil in Northern Shaanxi of China. AB - The impacts of petroleum contamination on the litter decomposition of shrub-grass land would directly influence nutrient cycling, and the stability and function of ecosystem. Ten common shrub and grass species from Yujiaping oil deposits were studied. Litters from these species were placed into litterbags and buried in petroleum-contaminated soil with 3 levels of contamination (slight, moderate and serious pollution with petroleum concentrations of 15, 30 and 45 g/kg, respectively). A decomposition experiment was then conducted in the lab to investigate the impacts of petroleum contamination on litter decomposition rates. Slight pollution did not inhibit the decomposition of any litters and significantly promoted the litter decomposition of Hippophae rhamnoides, Caragana korshinskii, Amorpha fruticosa, Ziziphus jujuba var. spinosa, Periploca sepium, Medicago sativa and Bothriochloa ischaemum. Moderate pollution significantly inhibited litter decomposition of M. sativa, Coronilla varia, Artemisia vestita and Trrifolium repens and significantly promoted the litter decomposition of C. korshinskii, Z. jujuba var. spinosa and P. sepium. Serious pollution significantly inhibited the litter decomposition of H. rhamnoides, A. fruticosa, B. ischaemum and A. vestita and significantly promoted the litter decomposition of Z. jujuba var. spinosa, P. sepium and M. sativa. In addition, the impacts of petroleum contamination did not exhibit a uniform increase or decrease as petroleum concentration increased. Inhibitory effects of petroleum on litter decomposition may hinder the substance cycling and result in the degradation of plant communities in contaminated areas. PMID- 26141900 TI - Zebrafish as a possible bioindicator of organic pollutants with effects on reproduction in drinking waters. AB - Organic contaminants can be detected at low concentrations in drinking water, raising concerns for human health, particularly in reproduction. In this respect, we attempted to use the zebrafish as a bioindicator to detect the possible presence of these substances in drinking water, aiming to define the most relevant parameters to detect these substances, which particularly affect the development and reproduction of zebrafish. To this end, batches of 30 embryos with the chorion intact were cultured in drinking waters from different sources, throughout their full life-cycle up to 5 months, in 20 L tanks. Six replicates were performed in all water groups, with a total of 24 aquariums. Two generations (F0 and F1) were studied and the following parameters were tested: in the F0 generation, survival and abnormality rates evaluated at 5 dpf (days post fertilization) and at 5 mpf (months post-fertilization), the onset of spawning and the fertility rate from 3 mpf to 5 mpf, and the sex ratio and underdeveloped specimens at 5 mpf. Furthermore, in the F0 offspring (F1), survival and abnormality rates were evaluated at 5 dpf and the hatching rate at 72 hpf. These results revealed that the hatching rate is the most sensitive parameter to distinguish different levels of effects between waters during the early life stages, whereas the rate of underdeveloped specimens is more suitable at later life stages. Regarding adult reproduction, fertility rate was the most sensitive parameter. The possible reversibility or accumulative nature of such effects will be studied in future work. PMID- 26141901 TI - Haze formation in China: Importance of secondary aerosol. PMID- 26141902 TI - [Support of breastfeeding by health professionals: integrative review of the literature]. AB - OBJECTIVE: To review the literature in order to evaluate how health professionals promote and support breastfeeding. DATA SOURCES: Studies from the following databases were retrieved: Scopus, PubMed, Medline, Lilacs, SciELO, Web of Science and Cumulative Index to Nursing and Allied Health Literature (Cinahl). The descriptors "breastfeeding", "professional role" and "patient care team" were used in the research. The review was limited to articles in Portuguese, Spanish, and English published between 1997 and 2013. DATA SYNTHESIS: The search retrieved 1,396 studies, 18 of which were selected for being directly relevant to the main question. The review showed that breastfeeding is a challenge for health professionals, regardless of their specialization, as they have to face a demand that requires skill and sensibility, for which they are not prepared. Health professionals have considered breastfeeding a purely instinctive and biological act. Moreover, it is noticeable that many of them possess theoretical expertise on the subject, but lack the practical skills. CONCLUSIONS: Health professionals need to be better trained to work on promoting breastfeeding, whether by health and medical schools or by healthcare administrators, in order to consolidate multiprofessional teams committed to maternal-infant health. PMID- 26141903 TI - [Vitamin D in children and adolescents with sickle cell disease: an integrative review]. AB - OBJECTIVE: To review the literature about the prevalence of vitamin D deficiency and its consequences in children and adolescents with sickle-cell disease. DATA SOURCES: The literature survey was performed through the bibliographic databases Medline; U.S. National Library of Medicine and National Institutes of Health (PubMed); Literatura Latino-Americana e do Caribe em Ciencias da Saude (Lilacs), and the Cochrane Library. The keywords were selected using Medical Heading Terms (MeSH): "Vitamin D" OR "Vitamin D deficiency" AND "Anemia, Sickle Cell" AND "Child" AND "Adolescent". The search was limited to articles in English, Spanish and Portuguese, published until April 2014. DATA SYNTHESIS: Eleven articles were selected among the 18 found. In 6 of the 11 studies, serum levels of vitamin D in children and/or adolescents with sickle-cell anemia were low. The prevalence of vitamin D deficiency in patients with sickle-cell anemia exceeded that of the comparison group. The low intake of vitamin D, seasonality, exposure to sun, increased metabolism associated with the hemoglobinopathy, and age increase were factors associated with the deficiency. There was an association between a significant vitamin D deficiency and bone weakness and painful crises. There was a positive correlation between increased levels of vitamin D by supplementation and functional, physical capacity. CONCLUSIONS: The vitamin D deficiency in children and adolescents with sickle-cell disease is prevalent and requires further studies to demonstrate its association with comorbidities and possible benefits of vitamin D supplementation. PMID- 26141904 TI - [Obstruction of peripherally inserted central catheters in newborns: prevention is the best intervention]. PMID- 26141906 TI - Validation of a smartphone-based measurement tool for the quantification of level walking. AB - INTRODUCTION: It is important to assess and quantify gait in order to determine the severity of impairments during gait and to evaluate therapeutic interventions. However, laboratory gait assessment is expensive and time consuming and there is a lack of an easily applicable tool for the quantification of gait in clinical practice. The aim of this study was to validate a smartphone based measurement tool for the quantification of level walking. METHODS: Vertical center of mass displacement and step duration of 22 healthy young adults were assessed by a smartphone application and a motion capture system. Intra-session reliability was evaluated by repeated-measures ANOVA, intraclass correlation coefficient (ICC), and standard error of measurement. In order to evaluate the concurrent validity of the smartphone application, smartphone- and motion capture derived values were compared by Pearson correlation coefficient and Bland-Altman limits of agreement. RESULTS: Six out of eight variables derived by the smartphone application showed an excellent reliability (ICC>=0.75) and all variables correlated significantly with measurements of the motion capture system with moderate to strong correlations ranging from 0.61 to 0.92. CONCLUSION: The results showed a great potential of the smartphone application to be a user friendly and valid tool for the assessment of gait in clinical practice. Further research needs to investigate whether the smartphone application is able to detect differences in gait patterns following therapeutic or orthopedic interventions and whether it is valid for the quantification of gait in people with movement disorders. PMID- 26141905 TI - Balance differences in people with Parkinson disease with and without freezing of gait. AB - BACKGROUND: Freezing of gait (FOG) is a relatively common and remarkably disabling impairment associated with Parkinson disease (PD). Laboratory-based measures indicate that individuals with FOG (PD+FOG) have greater balance deficits than those without FOG (PD-FOG). Whether such differences also can be detected using clinical balance tests has not been investigated. We sought to determine if balance and specific aspects of balance, measured using Balance Evaluation Systems Test (BESTest), differs between PD+FOG and PD-FOG. Furthermore, we aimed to determine if time-efficient clinical balance measures (i.e. Mini-BESTest, Berg Balance Scale (BBS)) could detect balance differences between PD+FOG and PD-FOG. METHODS: Balance of 78 individuals with PD, grouped as either PD+FOG (n=32) or PD-FOG (n=46), was measured using the BESTest, Mini BESTest, and BBS. Between-groups comparisons were conducted for these measures and for the six sections of the BESTest using analysis of covariance. A PD composite score was used as a covariate. RESULTS: Controlling for motor sign severity, PD duration, and age, PD+FOG had worse balance than PD-FOG when measured using the BESTest (p=0.008, F=7.35) and Mini-BESTest (p=0.002, F=10.37), but not the BBS (p=0.27, F=1.26). BESTest section differences were noted between PD+FOG and PD-FOG for reactive postural responses (p<0.001, F=14.42) and stability in gait (p=0.003, F=9.18). CONCLUSIONS: The BESTest and Mini-BESTest, which specifically assessed reactive postural responses and stability in gait, were more likely than the BBS to detect differences in balance between PD+FOG and PD-FOG. Because it is more time efficient to administer, the Mini-BESTest may be the preferred tool for assessing balance deficits associated with FOG. PMID- 26141907 TI - Keep the driver in control: Automating automobiles of the future. AB - Automated automobiles will be on our roads within the next decade but the role of the driver has not yet been formerly recognised or designed. Rather, the driver is often left in a passive monitoring role until they are required to reclaim control from the vehicle. This research aimed to test the idea of driver initiated automation, in which the automation offers decision support that can be either accepted or ignored. The test case examined a combination of lateral and longitudinal control in addition to an auto-overtake system. Despite putting the driver in control of the automated systems by enabling them to accept or ignore behavioural suggestions (e.g. overtake), there were still issues associated with increased workload and decreased trust. These issues are likely to have arisen due to the way in which the automated system has been designed. Recommendations for improvements in systems design have been made which are likely to improve trust and make the role of the driver more transparent concerning their authority over the automated system. PMID- 26141908 TI - The future flight deck: Modelling dual, single and distributed crewing options. AB - It is argued that the barrier to single pilot operation is not the technology, but the failure to consider the whole socio-technical system. To better understand the socio-technical system we model alternative single pilot operations using Cognitive Work Analysis (CWA) and analyse those models using Social Network Analysis (SNA). Four potential models of single pilot operations were compared to existing two pilot operations. Using SOCA-CAT from CWA, we were able to identify the potential functional loading and interactions between networks of agents. The interactions formed the basis on the SNA. These analyses potentially form the basis for distributed system architecture for the operation of a future aircraft. The findings from the models suggest that distributed crewing option could be at least as resilient, in network architecture terms, as the current dual crewing operations. PMID- 26141910 TI - Synthesis and biological evaluation of a new series of 2-amino-3-aroyl thiophene derivatives as agonist allosteric modulators of the A1 adenosine receptor. A position-dependent effect study. AB - The 2-amino-3-(p-chlorobenzoyl)thiophene scaffold has been widely employed as a pharmacophore for the identification of small molecules acting as allosteric modulators at the adenosine A1 receptor. A new series of 2-amino-3-(p chlorobenzoyl)-4-benzyl-5-arylthiophene derivatives, characterized by the absence as well as the presence of electron-releasing or electron-withdrawing groups on the phenyl ring at the 4- and 5-positions of the thiophene ring, were identified as positive allosteric enhancers at the adenosine A1 receptor in binding (saturation, competition and dissociation kinetics) and functional assays. To better understand the positional requirements of substituents on the 2-amino-3-(p chlorobenzoyl)thiophene core, the corresponding regioisomeric 4-aryl-5 benzylthiophene analogues were synthesized and found to possess reduced allosteric enhancer activity. PMID- 26141909 TI - Bringing it home: expanding the local reach of dissemination and implementation training via a university-based workshop. AB - BACKGROUND: Currently, national training programs do not have the capacity to meet the growing demand for dissemination and implementation (D&I) workforce education and development. The Colorado Research in Implementation Science Program (CRISP) developed and delivered an introductory D&I workshop adapted from national programs to extend training reach and foster a local learning community for D&I. METHODS: To gauge interest and assess learning needs, a pre-registration survey was administered. Based on feedback, a 1.5-day workshop was designed. Day 1 introduced D&I frameworks, strategies, and evaluation principles. Local and national D&I experts provided ignite-style talks on key lessons followed by panel discussion. Breakout sessions discussed community engagement and applying for D&I grants. A workbook was developed to enhance the training and provided exercises for application to an individual's projects. Day 2 offered expert-led mentoring sessions with selected participants who desired advanced instruction. Two follow up surveys (immediate post-workshop, 6 months) assessed knowledge gained from participation and utilization of workshop content. RESULTS: Ninety-three workshop registrants completed an assessment survey to inform workshop objectives and curriculum design; 43 % were new and 54 % reported a basic understanding of the D&I field. Pre-registrants intended to use the training to "apply for a D&I grant" (73 %); "incorporate D&I into existing projects" (76 %), and for quality improvement (51 %). Sixty-eight individuals attended Day 1; 11 also attended Day 2 mentoring sessions. In the 1-week post-workshop survey (n = 34), 100 % strongly agreed they were satisfied with the training; 97 % strongly agreed the workshop workbook was a valuable resource. All Day 2 participants strongly agreed that working closely with faculty and experts increased their overall confidence. In the 6-month follow-up evaluation (n = 23), evidence of new D&I-related manuscripts and grant proposals was found. Training materials were published online ( www.ucdenver.edu/implementation/workshops ) and disseminated via the National Institutes of Health (NIH) Clinical and Translational Science Awards Consortium. To sustain reach, CRISP adapted the materials into an interactive e book ( www.CRISPebooks.org ) and launched a new graduate course. CONCLUSIONS: Local D&I training workshops can extend the reach of national training programs. PMID- 26141911 TI - Design, synthesis and antiproliferative activity of novel heterobivalent hybrids based on imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole scaffolds. AB - Heterobivalent ligands constituted by two different pharmacophores that bind to different molecular targets or to two distinct sites on the same molecular target could be one of the methods used for the treatment of cancer. In view of the importance of imidazo[1,2-b][1,3]thiazole and imidazo[1,2-b][1,3,4]thiadiazole as privileged structures for the preparation of novel anticancer agents, we decided to explore the synthesis and biological evaluation of molecular conjugates comprising these fused bicyclic systems tethered at their C-6 position by a meta (alpha-bromoacryloylamido)phenyl moiety. We found that most of the hybrid compounds displayed high antiproliferative activity toward a wide panel of cancer cell lines, with one-digit micromolar to submicromolar 50% inhibitory concentrations (IC50). We have observed that selected compounds 7d, 7e, 7n and 8c induced apoptosis, which was associated with the release of cytochrome c and cleavage of multiple caspases. Overexpression of the protective mitochondrial protein Bcl-2 did not confer protection to cell death induced by these compounds. PMID- 26141912 TI - Association of Ideal Cardiovascular Health and Long-term Healthcare Costs. AB - INTRODUCTION: The American Heart Association's (AHA's) 2020 Strategic Impact Goals introduced the concept of ideal cardiovascular (CV) health based on seven health factors and behaviors associated with lower CV disease (CVD) risk. The association between CV health and healthcare costs has not been reported; therefore, we evaluated the association between CV health profile and later-life healthcare costs. METHODS: Cooper Center Longitudinal Study participants (N=4,906; mean age, 56 years) receiving Medicare coverage from 1999 to 2009 were included. CV health behaviors (diet, physical activity, BMI, smoking) and CV health factors (blood pressure, total cholesterol, blood glucose) were categorized as unfavorable (zero to two ideal components); intermediate (two to four); and favorable (five to seven). Healthcare costs were cumulated from Medicare claims data, adjusted for inflation. Associations between midlife CV health status and non-CVD and CVD-related costs were estimated using multivariable quantile regression. Analyses were conducted in 2013 and 2014. RESULTS: Favorable CV health was prevalent in 14.8% of men and 30.1% of women, with <1% having ideal levels of all health metrics. After 31,945 person-years of Medicare follow-up, individuals with favorable CV health exhibited 24.9% (95% CI=11.7%, 36.0%) lower median annual non-CVD costs and 74.5% (57.5%, 84.7%) lower median CVD costs than those with unfavorable CV health. Annualized differences were greater for non-CVD costs than for CVD costs ($1,175 vs $566). CONCLUSIONS: Having more ideal CV health components in middle age, as outlined by the AHA 2020 Goals, is associated with lower non-CVD and CVD healthcare costs in later life. PMID- 26141913 TI - Weight Advice Associated With Male Firefighter Weight Perception and Behavior. AB - INTRODUCTION: The high prevalence of overweight and obesity threatens the health and safety of the fire service. Healthcare professionals may play an important role in helping firefighters achieve a healthy weight by providing weight loss counseling to at-risk firefighters. This study characterizes the impact of healthcare professional weight loss advice on firefighter weight perceptions and weight loss behaviors among overweight and obese male firefighters. METHODS: A national sample of 763 overweight and obese male firefighters who recalled visiting a healthcare provider in the past 12 months reported information regarding healthcare visits, weight perceptions, current weight loss behaviors, and other covariates in 2011-2012. Analyzed in 2013, four unique multilevel logistic regression models estimated the association between healthcare professional weight loss advice and the outcomes of firefighter-reported weight perceptions, intentions to lose weight, reduced caloric intake, and increased physical activity. RESULTS: Healthcare professional weight loss advice was significantly associated with self-perception as overweight (OR=4.78, 95% CI=2.16, 10.57) and attempted weight loss (OR=2.06, 95% CI=1.25, 3.38), but not significantly associated with reduced caloric intake (OR=1.26, 95% CI=0.82, 1.95) and increased physical activity (OR=1.51, 95% CI=0.89, 2.61), after adjusting for confounders. CONCLUSIONS: Healthcare professional weight loss advice appears to increase the accuracy of firefighter weight perceptions, promote weight loss attempts, and may encourage dieting and physical activity behaviors among overweight firefighters. Healthcare providers should acknowledge their ability to influence the health behaviors of overweight and obese patients and make efforts to increase the quality and frequency of weight loss recommendations for all firefighters. PMID- 26141914 TI - Acceptable and Preferred Cervical Cancer Screening Intervals Among U.S. Women. AB - INTRODUCTION: Current U.S. cervical cancer screening guidelines recommend a 3- or 5-year screening interval depending on age and screening modality. However, many women continue to be screened annually. The purpose of this study is to investigate U.S. women's self-reported frequency of cervical cancer screening, acceptance of an extended screening interval (once every 3-5 years), and preferred screening options. METHODS: Data from a 2012 web-based survey of U.S. women aged >=18 years who had not undergone a hysterectomy or been diagnosed with cervical cancer (N=1,380) were analyzed in 2014. Logistic regression models of extended screening interval use, acceptance, and preference were developed. RESULTS: Annual Pap testing was the most widely used (48.5%), accepted (61.0%), and preferred (51.1%) screening option. More than one third of respondents (34.4%) indicated that an extended screening interval would be acceptable, but only 6.3% reported that they were currently screened on an extended interval. Women who preferred an extended screening interval (32.9% of those willing to accept regular screening) were more likely to report no primary care visits during the last 12 months (AOR=2.05, p<0.003), no history of abnormal Pap test results (AOR=1.71, p=0.013), and that their last Pap test was performed by an internist/family practitioner rather than an obstetrician-gynecologist (AOR=2.03, p<0.001). CONCLUSIONS: U.S. women's acceptance of and preference for an extended cervical cancer screening interval appears to be more widespread than utilization. Strategies to educate women about the reasoning behind recommendations for less-than-annual testing and to foster informed preferences should be devised and evaluated. PMID- 26141915 TI - Predictors of Depression Stigma in Medical Students: Potential Targets for Prevention and Education. AB - INTRODUCTION: Suicide rates are higher among U.S. physicians than the general population. Untreated depression is a major risk factor, yet depression stigma presents a barrier to treatment. This study aims to identify early career indications of stigma among physicians-in-training and to inform the design of stigma-reduction programs. METHODS: A cross-sectional student survey administered at a large, Midwestern medical school in fall 2009 included measures of depression symptoms, attitudes toward mental health, and potential sources of depression stigma. Principal components factor analysis and linear regression were used to examine stigma factors associated with depression in medical students. RESULTS: The response rate was 65.7%, with 14.7% students reporting a previous depression diagnosis. Most students indicated that, if depressed, they would feel embarrassed if classmates knew. Many believed that revealing depression could negatively affect professional advancement. Factor analyses revealed three underlying stigma constructs: personal weakness, public devaluation, and social/professional discrimination. Students associating personal weakness with depression perceived medication as less efficacious and the academic environment as more competitive. Those endorsing public stigma viewed medication and counseling as less efficacious and associated depression with an inability to cope. Race, gender, and diagnosis of past/current depression also related to beliefs about stigma. Depression measures most strongly predicted stigma associated with personal weakness and social/professional discrimination. CONCLUSIONS: Recommendations for decreasing stigma among physicians-in-training include consideration of workplace perceptions, depression etiology, treatment efficacy, and personal attributes in the design of stigma reduction programs that could facilitate help-seeking behavior among physicians throughout their career. PMID- 26141916 TI - A Lagrangian Approach for Calculating Microsphere Deposition in a One-Dimensional Lung-Airway Model. AB - Using the open-source software openfoam as the solver, a novel approach to calculate microsphere transport and deposition in a 1D human lung-equivalent trumpet model (TM) is presented. Specifically, for particle deposition in a nonlinear trumpetlike configuration a new radial force has been developed which, along with the regular drag force, generates particle trajectories toward the wall. The new semi-empirical force is a function of any given inlet volumetric flow rate, micron-particle diameter, and lung volume. Particle-deposition fractions (DFs) in the size range from 2 MUm to 10 MUm are in agreement with experimental datasets for different laminar and turbulent inhalation flow rates as well as total volumes. Typical run times on a single processor workstation to obtain actual total deposition results at comparable accuracy are 200 times less than that for an idealized whole-lung geometry (i.e., a 3D-1D model with airways up to 23rd generation in single-path only). PMID- 26141917 TI - Wilderness Medicine Curricular Content in Emergency Medicine Residency Programs. PMID- 26141918 TI - Lyme Disease: What the Wilderness Provider Needs to Know. AB - Lyme disease is a multisystem tickborne illness caused by the spirochete Borrelia burgdorferi and is the most common vectorborne disease in the United States. Prognosis after initiation of appropriate antibiotic therapy is typically good if treated early. Wilderness providers caring for patients who live in or travel to high-incidence Lyme disease areas should be aware of the basic biology, epidemiology, clinical manifestations, and treatment of Lyme disease. PMID- 26141919 TI - A Rare Case of Vaginal Bleeding in a Child Due to a Leech Bite and Review of the Literature. PMID- 26141920 TI - The UPLOADS Project: Development of an Australian National Incident Dataset for Led Outdoor Activities. PMID- 26141921 TI - Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: Focus on sample preparation and derivatization conditions. AB - Protein oxidation is involved in regulatory physiological events as well as in damage to tissues and is thought to play a key role in the pathophysiology of diseases and in the aging process. Protein-bound carbonyls represent a marker of global protein oxidation, as they are generated by multiple different reactive oxygen species in blood, tissues and cells. Sample preparation and stabilization are key steps in the accurate quantification of oxidation-related products and examination of physiological/pathological processes. This review therefore focuses on the sample preparation processes used in the most relevant methods to detect protein carbonyls after derivatization with 2,4-dinitrophenylhydrazine with an emphasis on measurement in plasma, cells, organ homogenates, isolated proteins and organelles. Sample preparation, derivatization conditions and protein handling are presented for the spectrophotometric and HPLC method as well as for immunoblotting and ELISA. An extensive overview covering these methods in previously published articles is given for researchers who plan to measure protein carbonyls in different samples. PMID- 26141923 TI - Study on Metal Concentrations in Tissues of Mallard and Pochard from Two Major Wintering Sites in Southeastern Caspian Sea, Iran. AB - We examined concentrations of cadmium, chromium, iron, lead and zinc in the kidney, liver, and pectoral muscle of Mallards (Anas platyrhynchos; n = 30) and Pochards (Aythya ferina; n = 30) from two important wintering sites in the southeastern Caspian Sea in the winter of 2012. Mean lead concentrations (ug g( 1) ww) in livers (2.36 +/- 1.00) of Pochard and in kidneys (3.43 +/- 0.91) of Mallard exceeded the exposure threshold levels in liver (1.5 ug g(-1) ww) and kidney (3 ug g(-1) ww) of waterfowl. Mean cadmium concentrations in livers (1.63 +/- 0.66) of Pochards exceeded the background level of this metal in liver (1 ug g(-1) ww) of waterfowl. Chromium, iron and zinc concentrations were within the normal range as reported in other duck studies. Gender-related and inter-specific variation of metal concentrations in analyzed tissues were observed (t test, p < 0.05). Our results indicated that waterfowl using the Miankalah and Gomishan International Wetlands are being exposed to elevated concentrations of cadmium and lead. PMID- 26141922 TI - Effect of high glucose concentrations on human erythrocytes in vitro. AB - Exposure to high glucose concentrations in vitro is often employed as a model for understanding erythrocyte modifications in diabetes. However, effects of such experiments may be affected by glucose consumption during prolonged incubation and changes of cellular parameters conditioned by impaired energy balance. The aim of this study was to compare alterations in various red cell parameters in this type of experiment to differentiate between those affected by glycoxidation and those affected by energy imbalance. Erythrocytes were incubated with 5, 45 or 100mM glucose for up to 72 h. High glucose concentrations intensified lipid peroxidation and loss of activities of erythrocyte enzymes (glutathione S transferase and glutathione reductase). On the other hand, hemolysis, eryptosis, calcium accumulation, loss of glutathione and increase in the GSSG/GSH ratio were attenuated by high glucose apparently due to maintenance of energy supply to the cells. Loss of plasma membrane Ca(2+)-ATPase activity and decrease in superoxide production were not affected by glucose concentration, being seemingly determined by processes independent of both glycoxidation and energy depletion. These results point to the necessity of careful interpretation of data obtained in experiments, in which erythrocytes are subject to treatment with high glucose concentrations in vitro. PMID- 26141924 TI - In vitro hydrodynamic evaluation of a biovalve with stent (tubular leaflet type) for transcatheter pulmonary valve implantation. AB - We have been developing an autologous heart valve-shaped tissue with a stent (stent-biovalve) for transcatheter pulmonary valve implantation (TPVI) using "in body tissue architecture" technology. In this study, the hydrodynamic performance of a stent-biovalve with tubular leaflets was evaluated by changing its leaflet height in an in vitro test in order to determine the appropriate stent-biovalve form for the pulmonary valve. A specially designed, self-expandable, stent mounted, cylindrical acrylic mold was placed in a dorsal subcutaneous pouch of goat, and the implant was extracted 2 months later. Only the cylindrical acrylic mold was removed from the implant, and a tubular hollow structure of membranous connective tissue impregnated with the stent strut was obtained. Half of tubular tissue was completely folded in half inwards, and 3 commissure parts were connected to form 3 leaflets, resulting in the preparation of a stent-biovalve with tubular leaflets (25-mm ID). The stent-biovalve with adjusting leaflet height (13, 14, 15, 17, 20, and 25 mm) was fixed to a specially designed pulsatile mock circulation circuit under pulmonary valve conditions using 37 degrees C saline. The mean pressure difference and effective orifice area were better than those of the biological valve. The lowest and highest leaflet heights had a high regurgitation rate due to lack of coaptation or prevention of leaflet movement, respectively. The lowest regurgitation (ca. 11%) was observed at a height of 15 mm. The leaflet height was found to significantly affect the hydrodynamics of stent-biovalves, and the existence of an appropriate leaflet height became clear. PMID- 26141925 TI - Social status modulates the neural response to unfairness. AB - In human society, which is organized by social hierarchies, resources are usually allocated unequally and based on social status. In this study, we analyze how being endowed with different social statuses in a math competition affects the perception of fairness during asset allocation in a subsequent Ultimatum Game (UG). Behavioral data showed that when participants were in high status, they were more likely to reject unfair UG offers than in low status. This effect of social status correlated with activity in the right anterior insula (rAI) and with the functional connectivity between the rAI and a region in the anterior middle cingulate cortex, indicating that these two brain regions are crucial for integrating contextual factors and social norms during fairness perception. Additionally, there was an interaction between social status and UG offer fairness in the amygdala and thalamus, implicating the role of these regions in the modulation of social status on fairness perception. These results demonstrate the effect of social status on fairness perception and the potential neural underpinnings for this effect. PMID- 26141926 TI - Cardiovascular and respiratory mortality attributed to ground-level ozone in Ahvaz, Iran. AB - Ahvaz, the capital city of Khuzestan Province, which produces Iran's most oil, is on the rolls of fame in view of air pollution. It has also suffered from dust storm during the recent two decades. So, emissions from transportation systems, steel, oil, black carbon, and other industries as anthropogenic sources and dust storm as a new phenomenon are two major concerns of air pollution in Ahvaz. Without any doubt, they can cause many serious problems for the environment and humans in this megacity. The main objective of the present study was to estimate the impact of ground-level ozone (GLO) as a secondary pollutant on human heath. Data of GLO in four monitoring stations were collected at the first step and they were processed and at the final step they were inserted to a health effect model. Findings showed that cumulative cases of cardiovascular and respiratory deaths which attributed to GLO were 43 and 173 persons, respectively. Corresponding RR for these two events were 1.008 (95% CI) and 1.004 (95% CI), respectively. Although we did not provide a distinction between winter and summer in case of mentioned mortalities attributed to GLO, ozone concentrations in winter due to more fuel consumption and sub adiabatic condition in tropospheric atmospherewere higher than those GLO in summer. PMID- 26141927 TI - Community-acquired Clostridium difficile infection in children: A retrospective study. AB - BACKGROUND: Community acquired-Clostridium difficile infection (CDI) has increased also in children in the last years. AIMS: To determine the incidence of community-acquired CDI and to understand whether Clostridium difficile could be considered a symptom-triggering pathogen in infants. METHODS: A five-year retrospective analysis (January 2007-December 2011) of faecal specimens from 124 children hospitalized in the Niguarda Ca' Granda Hospital for prolonged or muco haemorrhagic diarrhoea was carried out. Stool samples were evaluated for common infective causes of diarrhoea and for Clostridium difficile toxins. Patients with and without CDI were compared for clinical characteristics and known risk factors for infection. RESULTS: Twenty-two children with CDI were identified in 5 years. An increased incidence of community-acquired CDI was observed, ranging from 0.75 per 1000 hospitalizations in 2007 to 9.8 per 1000 hospitalizations in 2011. Antimicrobial treatment was successful in all 19 children in whom it was administered; 8/22 CDI-positive children were younger than 2 years. No statistically significant differences in clinical presentation were observed between patients with and without CDI, nor in patients with and without risk factors for CDI. CONCLUSIONS: Our study shows that Clostridium difficile infection is increasing and suggests a possible pathogenic role in the first 2 years of life. PMID- 26141929 TI - Relationship between red blood cell transfusion requirements and severity of renal disease during the acute stage of hemolytic uremic syndrome. AB - BACKGROUND: We performed a retrospective evaluation of patients with diarrhea associated hemolytic uremic syndrome (D + HUS) with the aims of: (1) determining the rate of red blood cell (RBC) transfusions; (2) establishing the relationship between need for RBC transfusion and severity of renal involvement; (3) determining whether precise measurements of lactic dehydrogenase (LDH) levels can predict the rate of hemolysis and severity of renal disease. METHODS: A total of 288 patients with D + HUS were retrospectively divided into three groups based on dialysis treatment: group 1, no dialysis treatment (144 patients); group 2, dialysis for 1-10 days (67 patients); group 3, dialysis for >=11 days (77 patients). RESULTS: Of the patients in groups 1, 2 and 3, 73.6, 86.5 and 83.1%, respectively, required at least one RBC transfusion. The number of RBC transfusions in groups 1, 2 and 3 was 163, 107 and 162, respectively. Comparison of the groups revealed that the number of RBC transfusions was significantly higher in patients in groups 2 and 3 than in those in group 1 (p = 0.0001). Most RBC transfusions (94.2%) occurred during the first 2 weeks of the disease. The median peak LDH level was 2091 U/l in 32 patients with no RBC transfusion (group A), 3900 U/l in 73 patients with one transfusion (group B) and 6378 U/l in 62 patients with two or more transfusions (group C). Patients who received two or more RBC transfusions had a significantly higher median peak LDH level than those who did not receive RBC transfusions or received only one transfusion. This difference was also observed between patients who received only one RBC transfusion and those who did not receive any transfusions (p < 0.00001). Comparison of LDH levels on admission and peak LDH levels among patients in groups A, B and C revealed that 28/32 patients in group A, 56/73 patients in group B and 33/62 patients in group C had a stable LDH level, suggesting that patients with a stable LDH level require fewer RBC transfusions (p <= 0.006). Finally, we evaluated the possibility of an association between peak LDH levels and the degree of renal disease. The median peak LDH level in patients of group 1, 2 and 3 was 3538 (range 756-9373), 5165 (451-9205) and 7510 (1,145-16,340) U/l, respectively. Patients with >10 days of dialysis (group 3) had the highest LDH levels, followed by patients with 1-10 days of dialysis (group 2) and then by patients with no dialysis requirements (group 1) (p < 0.00001). CONCLUSIONS: The rate of RBC transfusion was higher in patients with the most severe renal injury, and most were performed during the first 2 weeks of the disease. Patients with stable LDH levels seemed to require fewer RBC transfusions. Median peak LDH levels were significantly higher in the group of patients with the most severe renal disease. PMID- 26141928 TI - Autophagy in renal diseases. AB - Autophagy is the cell biology process in which cytoplasmic components are degraded in lysosomes to maintain cellular homeostasis and energy production. In the healthy kidney, autophagy plays an important role in the homeostasis and viability of renal cells such as podocytes and tubular epithelial cells and of immune cells. Recently, evidence is mounting that (dys)regulation of autophagy is implicated in the pathogenesis of various renal diseases, and might be an attractive target for new renoprotective therapies. In this review, we provide an overview of the role of autophagy in kidney physiology and kidney diseases. PMID- 26141930 TI - Norepinephrine responses in rat renal and femoral veins are reinforced by vasoconstrictor prostanoids. AB - Norepinephrine (NE) responses are larger in renal and femoral veins compared to phenylephrine (PE). These differences may be due to the subtypes of adrenoceptor involved in these responses or to the involvement of local modulatory mechanisms. Therefore, the present study investigated in organ bath the adrenoceptor subtypes involved in the NE and PE responses in both renal and femoral veins as well as the influence of local mechanisms related to NO and to prostanoids upon these responses. The obtained data showed that the NE responses in these veins were not significantly modified by the selective inhibition of beta1 or beta2 adrenoceptors as well as AT1 or AT2 receptors. However, yohimbine reduced the NE Rmax in renal veins and, in parallel, right shifted the NE concentration-response curves in femoral veins. In both veins, prazosin reduced the NE Rmax and the clonidine induced a measurable contraction. The endothelium removal attenuated the NE responses in femoral veins, thereby abolishing the differences of NE and PE responses. Furthermore, the NE responses in renal and femoral veins were attenuated by indomethacin, which suppressed the statistical difference in relation to the PE response. In conclusion, a synergism between alpha1- and alpha2-adrenoceptors is essential to assure full NE contractile responses in both renal and femoral veins. Thus, by acting simultaneously in these adrenoceptors, NE induces more pronounced contractile responses, in comparison to PE, not only in renal but also in femoral veins. Moreover, this pronounced NE response in both renal and femoral veins appears to involve endothelium-derived vasoconstrictor prostanoids. PMID- 26141931 TI - Contribution of oxidative stress and prostanoids in endothelial dysfunction induced by chronic fluoxetine treatment. AB - OBJECTIVES: The effects of chronic fluoxetine treatment were investigated on blood pressure and on vascular reactivity in the isolated rat aorta. METHODS AND RESULTS: Male Wistar rats were treated with fluoxetine (10 mg/kg/day) for 21 days. Fluoxetine increased systolic blood pressure. Chronic, but not acute, fluoxetine treatment increased the contractile response induced by phenylephrine, serotonin (5-HT) and KCl in endothelium-intact rat aortas. L-NAME and ODQ did not alter the contraction induced by phenylephrine and 5-HT in aortic rings from fluoxetine-treated rats. Tiron, SC-560 and AH6809 reversed the increase in the contractile response to phenylephrine and 5-HT in aortas from fluoxetine-treated rats. Fluoxetine treatment increased superoxide anion generation (O2(-)) and the expression of cyclooxygenase (COX)-1 in the rat aorta. Reduced expression of nNOS, but not eNOS or iNOS was observed in animals treated with fluoxetine. Fluoxetine treatment increased prostaglandin (PG)F2alpha levels but did not affect thromboxane (TX)B2 levels in the rat aorta. Reduced hydrogen peroxide (H2O2) levels and increased catalase (CAT) activity were observed after treatment. CONCLUSIONS: The major new finding of our study is that chronic fluoxetine treatment induces endothelial dysfunction, which alters vascular responsiveness by a mechanism that involves increased oxidative stress and the generation of a COX-derived vasoconstrictor prostanoid (PGF2alpha). Moreover, our results evidenced a relation between the period of treatment with fluoxetine and the magnitude in the increment of blood pressure. Finally, our findings raise the possibility that fluoxetine treatment increases the risk for vascular injury, a response that could predisposes to cardiovascular diseases. PMID- 26141932 TI - Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and Multidrug Resistance Protein 4 expression in human platelets. AB - Platelet Multidrug Resistance Protein 4 (MRP4)-overexpression has a role in reducing aspirin action in patients after by-pass surgery. Aspirin induces platelet MRP4 over-expression, through megakaryocytes genomic modulation. Aim of our work was to verify whether other non-steroidal antiinflammatory drugs (NSAIDs) enhance platelet MRP4 expression and evaluate platelet function in patients who overexpressed MRP4. We evaluated MRP4-mRNA in a human megakacaryoblastic cell line (DAMI), treated with both COX-2 inhibitor (celecoxib) and traditional NSAIDs (diclofenac and naproxen). Osteoarthritis patients, who reported to take NSAIDs twice a week for at least four continuous weeks and a control population, who didn't take any drugs during the previous month, were enrolled. We evaluated platelet MRP4 amount, by both mRNA levels and protein expression (Western-Blot) and ADP induced platelet aggregation. DAMI cells treated with celecoxib, diclofenac, and naproxen showed a significant increase in MRP4-mRNA expression compared to the mock culture. Osteoarthritis patient platelets presented a higher expression of MRP4 (both at mRNA and protein levels) and an increase in ADP-induced platelet aggregation compared to the control population. NSAID treatment induced platelet MRP4 overexpression. Osteoarthritis patients, who overexpress MRP4, showed platelet hyper-reactivity. These evidences could explain in part the increased cardiovascular risk present during NSAID treatment. PMID- 26141933 TI - Ayurveda and botanical drugs for epilepsy: Current evidence and future prospects. AB - The understanding of epilepsy has progressed since its earliest impression as a disease associated with paranormal and superstitious beliefs. Landmark advances have been made in deciphering the pathophysiological substrates involved in the disease process, and treatment advances have contributed significantly to ameliorating the seizures. However, disease-modifying agents are yet to be discovered. Ayurveda is a system of medicine that stresses a holistic approach to disease, and treatment is focused on disease modification and symptom management. Herbs form the core of Ayurveda medicine; though many of them have been studied for their anticonvulsant activity, very few actually mention the reference of these herbs in Ayurveda literature. Other therapeutic interventions used in Ayurveda are relatively unexplored, and future research will need to focus on this. The current manuscript briefly discusses the understanding of epilepsy as per Ayurveda and reviews herbs that have been studied for their anticonvulsant activity mentioned in Ayurveda literature. This article is part of a Special Issue entitled "Botanicals for Epilepsy". PMID- 26141934 TI - Incidence and mortality of super-refractory status epilepticus in adults. AB - OBJECTIVES: Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24h or more after the onset of anesthetic therapy. We defined the incidence and outcome of SRSE in adults in Finland. METHODS: We analyzed retrospectively the Finnish Intensive Care Consortium database in order to identify adult patients with SRSE treated in ICUs in Finland during a three-year period (2010-2012). The database consists of admissions to all 20 Finnish hospitals treating refractory SE (RSE) with general anesthesia in the intensive care unit (ICU). We included consecutive adult (16 years or older) patients with RSE and identified those who had SRSE. Patients with postanoxic etiologies were excluded. RESULTS: All five university hospitals and 10/15 of the central hospitals participated. The adult referral population of the study hospitals is 3.9 million, representing 91% of the total adult population of Finland. We identified 395 patients with ICU-treated RSE, 87 (22%) of whom were classified as having SRSE. This corresponds to an annual incidence of SRSE of 0.7/100,000 (95% confidence interval [CI]: 0.6-0.9). The one-year mortality rates were 36% (95% CI: 26-46%) for patients with SRSE and 22% (95% CI: 17-27%) for patients with RSE. Mortality was highest (63%) in patients with SRSE aged over 75 years. CONCLUSIONS: Approximately 20% of patients with RSE treated in Finnish ICUs progressed to having SRSE. The incidence of SRSE, 0.7/100,000, is about 5-10% of the incidence of SE. The mortality of patients with SRSE, 36%, was comparable to earlier studies and twofold higher than the mortality of patients with RSE. This article is part of a Special Issue entitled "Status Epilepticus". PMID- 26141935 TI - The functional significance of the skilled performance positivity: An update. AB - The skilled performance positivity (SPP) emerges approximately 450 ms after button presses in a skilled performance task (SPT) where the participant is required to initiate a visual sweep with a left-hand button press and then stop it with a right-hand button press within a predetermined time frame (ranging from 40 to 60 ms). The SPP has been thought to represent appraisal of performance results independent of the reafferent activity, and reported to reduce in amplitude following inaccurate timing performance. We hypothesized that reduced SPP on incorrect trials merely indicates superimposition of the feedback-related negativity (FRN) that is elicited by negative outcomes, because the right-hand button press not only stops the visual sweep but also presents visual feedback. Further, we assumed that the SPP essentially represents a P300 elicited by the visual feedback. To address these questions, we compared the SPT condition and a delayed-feedback (DFB) condition where feedback was presented approximately 1 s after the left-hand button press. We observed the SPP only in the SPT condition, and found feedback-elicited P300s in the DFB condition. Both of these positivities shared a similar scalp distribution. We also replicated the reduced SPP on incorrect trials that shared a similar topography with the FRN elicited by the negative feedback. According to these findings, it is reasonable to conclude that the SPP represents the feedback-elicited P300, and after incorrect performance an FRN is superimposed on it. PMID- 26141936 TI - Deep impact: sequencing embryo biopsy specimens at increasing depth. PMID- 26141937 TI - Is there a clinical future for GV manipulation? PMID- 26141938 TI - Inflammation and Cancer: What Can We Therapeutically Expect from Checkpoint Inhibitors? AB - Programmed death-ligand 1 (PD-L1) is a cell surface protein which is mainly expressed on immune cells as well as on cancer cells and functions as a co stimulatory molecule for T lymphocytes. It is capable of inducing apoptosis in T cells via PD-1 which leads to impaired cytokine production and loss of cytotoxicity of activated T-cells. This represents a possible escape mechanism for cancer cells. Tumor infiltration by mononuclear cells and tumor aggressiveness was found to be associated with PD-L1 expression. In light of possible autoimmunological side effects, it remains currently unclear which patient will benefit most from this novel therapeutic approach. Furthermore, immunohistochemistry for PD-L1 has not been well standardized until now. In addition, the combination of chemotherapy with checkpoint inhibitors in different clinical settings needs to be established for the near future in order to avoid overtreatment and also unnecessary cost expenditures for the health care system. PMID- 26141939 TI - Attenuated fibroblast growth factor 21 response to acute aerobic exercise in obese individuals. AB - BACKGROUND AND AIM: Fibroblast growth factor 21 (FGF21) is positively associated with body mass index, potentially as a compensatory mechanism to mediate obesity related metabolic and inflammatory insult due to chronic low-grade elevations of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). Therefore, FGF21 response in obese subjects and the associations with increased pro-inflammatory cytokines, insulin resistance, and energy utilization warrants investigation. METHODS AND RESULTS: Twenty four untrained subjects (12 obese and 12 normal-weight) performed 30 min of continuous submaximal aerobic exercise. Following exercise, obese subjects exhibited a blunted FGF21 response to exercise compared to normal-weight subjects as indicated by area-under-the-curves "with respect to increase" (AUCi) analyses (p = 0.005). Furthermore, while exercise-induced plasma FGF21 was not associated with any inflammatory cytokine (IL-6 and TNF-alpha) response, FGF21 AUCi was positively correlated with glucose AUCi (r = 0.495, p = 0.014), total relative energy expenditure (r = 0.562, p = 0.004), and relative maximal oxygen consumption (VO2max; r = 0.646, p = 0.001) in all subjects. CONCLUSION: Impaired cardiorespiratory fitness may influence the sensitivity of FGF21 response to acute exercise in obese individuals, potentially contributing to the attenuated metabolic response (e.g., glucose) and total exercise energy expenditure. Therefore, exercise training aimed at improving cardiorespiratory fitness and/or body composition may augment cardioprotective properties against obesity associated CVD through enhanced FGF21 flux. PMID- 26141940 TI - FABP4 plasma concentrations are determined by acquired metabolic derangements rather than genetic determinants. AB - BACKGROUND AND AIMS: Circulating FABP4 is strongly associated with metabolic and cardiovascular risk (CVR) and has been proposed as a new risk biomarker. Several FABP4 gene polymorphisms have been associated with protein expression in vitro and metabolic and vascular alterations in vivo. The aim of this study is to evaluate the impact of FABP4 polymorphisms on FABP4 plasma levels and subclinical arteriosclerosis in patients with obesity, metabolic syndrome (MS) or type 2 diabetes (T2DM). METHODS AND RESULTS: We studied 440 individuals with obesity, MS, T2DM or other cardiovascular risk conditions who attended the vascular medicine and metabolism unit of our hospital. Anamnesis, physical examination and anthropometry data were recorded. Standard biochemical parameters were determined. Plasma FABP4 concentrations were measured. Carotid intima-media thickness (cIMT) was assessed using ultrasonography. The following FABP4 gene single-nucleotide polymorphisms (SNPs) were analyzed: rs3834363, rs16909233, rs1054135, rs77878271, rs10808846 and rs8192688. None of the studied gene allele variants were hyper-represented in patients grouped according the presence of metabolic alterations nor were they associated with the FABP4 concentration. The FABP4 gene variants did not determine cIMT differences between the groups. In a multivariate analysis, gender and BMI, but not gene variants, significantly determined plasma FABP4 concentrations. CONCLUSIONS: In clinical settings, the circulating FABP4 levels are determined by the acquired metabolic derangements and not genetic variation. PMID- 26141941 TI - Improving diet recipe and cooking methods attenuates hyperphosphatemia in patients undergoing peritoneal dialysis. AB - BACKGROUND AND AIMS: Hyperphosphatemia is an independent predictor for cardiovascular and all-cause mortality in patients undergoing peritoneal dialysis (PD). The study aimed to investigate the effect of dietary intervention on reducing serum phosphate concentration in hyperphosphatemic PD patients. METHODS AND RESULTS: In this single-center clinical trial, 97 prevalent PD patients with serum phosphate concentration >= 1.6 mmol/l were allocated to the intervention (n = 48) or control (n = 49) group and followed up for 1 year. In addition to phosphate binder (calcium carbonate) therapy, patients in the intervention group were intensively educated to reduce phosphate-rich food intake and improve cooking methods. While stable in the control group (1.97 +/- 0.20 to 1.94 +/- 0.35 mmol/l, p > 0.05), the serum phosphate concentration decreased significantly in the intervention group (1.98 +/- 0.28 to 1.65 +/- 0.33 mmol/l, p = 0.015) concurrently with the drop in dietary phosphate intake (13.03 +/- 3.39 to 10.82 +/- 3.00 mg/kg ideal body weight/day, p = 0.001). Moreover, after 6 months of intervention, fewer patients needed to use calcium carbonate (from 64.6% to 41.5%, p = 0.029) and the medicine dose reduced significantly (from 2.25 (0, 3.94) to 0 (0, 1.50) g/day, p < 0.001). CONCLUSIONS: Our data indicated that intensive dietary intervention of reducing phosphate-rich food intake and improving cooking methods attenuated hyperphosphatemia in PD patients. It suggests that regular assessment of dietary phosphate intake and modification of diet recipe and cooking methods are essential for hyperphosphatemia treatment in PD patients in addition to phosphate binder therapy. PMID- 26141942 TI - Effect of aerobic exercise training followed by a low-calorie diet on metabolic syndrome risk factors in men. AB - BACKGROUND AND AIMS: Whether low-volume, high-intensity, interval training (HIIT) is an adequate exercise method for improving metabolic risk factors is controversial. Moreover, it is not known if performing a short-term, low-calorie diet intervention (LCDi) after a HIIT program affects risk factors. This study investigated how an 8-week, 3 times/week exercise intervention (EXi) incorporating either HIIT or moderate-intensity continuous training (MICT) followed by a 4-week LCDi affects risk factors. METHODS AND RESULTS: Twenty-six male workers with metabolic risk factors (47.4 +/- 7.1 years; cardiorespiratory capacity (VO2peak) of 28.5 +/- 3.9 ml/kg/min) were randomly assigned to either the HIIT (3 sets of 3-min cycling with a 2-min active rest between sets, 180 kcal) or MICT (45 min, 360 kcal) group. After the EXi, all subjects participated in a 4-week LCDi (4 counseling sessions). During the EXi, VO2peak improved more (P < 0.05) through HIIT (25.4 +/- 14.6%) than through MICT (14.9 +/- 12.8%), whereas improvements in body fat and HDL cholesterol were similar. During the LCDi, some risk factors improved further (P < 0.05) without any group differences, while VO2peak in the HIIT group decreased (P < 0.05) to the same level as in the MICT group. CONCLUSION: VO2peak increased more with HIIT than with MICT during the EXi despite HIIT having a lower exercise volume than MICT, but this advantage of HIIT promptly disappeared through detraining. An intervention strategy consisting of 8 weeks of either HIIT or MICT followed by a 4-week LCDi has a positive effect on metabolic risk factors. CLINICAL TRIAL REGISTRATION: UMIN11352. PMID- 26141943 TI - Fucoxanthin and lipid metabolism: A minireview. AB - AIMS: Accumulating data suggest that food supplementation with seaweeds which traditionally are an important part of food culture in South-East Asian countries might lead to essential health benefits. In this short review, we summarize findings from experimental studies on the effects of fucoxanthin (a carotenoid derived from brown seaweeds) on lipid metabolism, adiposity, and related conditions and discuss the possible underlying mechanisms. DATA SYNTHESIS: Supplementation of fucoxanthin or its derivatives consistently attenuated body and visceral fat weight gain, lipid accumulation in the liver, decreases insulin resistance, and improves the plasma lipid profile in rodents fed a high-fat diet. It should however be noted that in diabetic/obese KK-Ay mice with genetically compromised insulin signaling, fucoxanthin might increase the plasma levels of cholesterol and low-density lipoproteins. The anti-obesity effects of fucoxanthin are apparently mediated by the hormones leptin and adiponectin through their common target AMK-activated protein kinase, resulting in downregulation of lipogenic enzymes and upregulation of lipolytic enzymes. Fucoxanthin also suppresses adipocyte differentiation and induces the expression of uncoupling proteins in visceral adipose tissue. CONCLUSIONS: The results of experimental studies suggest that consumption of fucoxanthin and its derivatives as nutritional supplements is a promising option for prevention and treatment of obesity and a wide variety of related pathologies, including metabolic syndrome, type 2 diabetes, and heart disease. Yet, clinical trials are warranted to assess a therapeutic value of fucoxanthin. PMID- 26141944 TI - Effect of grain size on ultrasonic softening of pure aluminum. AB - The objective of this paper is to reveal the main cause of volume effects of ultrasonic vibrations on the plastic behavior of pure aluminum specimens. For this purpose, specimens with different grain sizes were made by ECAP. An experimental tensile test system was designed and made, in which the specimens could be excited by ultrasonic vibrations with a frequency of 20 kHz and amplitude of 5 MUm. Five specimens with grain sizes of 109, 38, 15, 7 and 0.97 MUm were prepared. Tensile tests of the specimens were performed at room temperature and at constant speed of 0.2 mm/min under static load and superimposed ultrasonic excitations. It was found that ultrasonic vibrations had a remarkable influence on the plastic behavior of pure aluminum and after applying ultrasonic vibrations, flow stress of the all specimens reduced. Reduction of flow stress was dependent on grain size. The specimens with the largest grain size of 109 MUm showed a flow stress reduction of 66% while finest grain size of 0.97 MUm, a reduction of 11.3% was observed. The result of the current study can help to understand the underlying mechanisms of ultrasonic softening. PMID- 26141945 TI - Heat Shock Protein 90 Is a Potential Therapeutic Target in Cholangiocarcinoma. AB - Cholangiocarcinoma is an aggressive malignancy with a poor prognosis, with no effective therapy other than surgical resection. Heat shock protein 90 (HSP90) is a key component of a multichaperone complex involved in the posttranslational folding of a number of client proteins, many of which play essential roles in tumorigenesis. Here, we attempted to clarify its prognostic significance and potential utility as a therapeutic target in cholangiocarcinoma. Immunohistochemical expression of HSP90 was assessed retrospectively in 399 cholangiocarcinoma cases and 17 human cholangiocarcinoma cell lines, along with the effect of a small-molecule HSP90 inhibitor (NVP-AUY922) on cholangiocarcinoma tumor growth and angiogenesis in human cholangiocarcinoma cell lines and xenografts. The positivity of HSP90 was 44.6% in intrahepatic cholangiocarcinoma (IHCC) and 32.8% in extrahepatic cholangiocarcinoma (EHCC), respectively. HSP90 expression was significantly associated with the 5-year survival rate for IHCC (P < 0.001) and EHCC (P < 0.001). HSP90 inhibition showed potent antiproliferative activity and reduced growth-associated signaling in human cholangiocarcinoma cells in vitro. Furthermore, treatment of cholangiocarcinoma xenograft-bearing mice with NVP-AUY922 significantly inhibited growth at doses far below the maximum-tolerated dose. HSP90 overexpression is a prognostic marker for cholangiocarcinoma. HSP90-targeted therapy may be an option for a subset of cholangiocarcinoma. PMID- 26141946 TI - Antitumor Effects of MEHD7945A, a Dual-Specific Antibody against EGFR and HER3, in Combination with Radiation in Lung and Head and Neck Cancers. AB - Human epidermal growth factor receptor family members (EGFR, HER2, HER3, and HER4) play important roles in tumorigenesis and response to cancer therapeutics. In this study, we evaluated the capacity of the dual-target antibody MEHD7945A that simultaneously targets EGFR and HER3 to modulate radiation response in lung and head and neck cancer models. Antitumor effects of MEHD7945A in combination with radiation were evaluated in cell culture and tumor xenograft models. Mechanisms that may contribute to increased radiation killing by MEHD7945A, including DNA damage and inhibition of EGFR-HER signaling pathways, were analyzed. Immunohistochemical analysis of tumor xenografts was conducted to evaluate the effect of MEHD7945A in combination with radiation on tumor growth and microenvironment. MEHD7945A inhibited basal and radiation-induced EGFR and HER3 activation resulting in the inhibition of tumor cell growth and enhanced radiosensitivity. MEHD7945A was more effective in augmenting radiation response than treatment with individual anti-EGFR or anti-HER3 antibodies. An increase in DNA double-strand breaks associated gamma-H2AX was observed in cells receiving combined treatment with MEHD7945A and radiation. Immunohistochemical staining evaluation in human tumor xenografts showed that MEHD7945A combined with radiation significantly reduced the expression of markers of tumor proliferation and tumor vasculature. These findings reveal the capacity of MEHD7945A to augment radiation response in lung and head and neck cancers. The dual EGFR/HER3 targeting action of MEHD7945A merits further investigation and clinical trial evaluation as a radiation sensitizer in cancer therapy. PMID- 26141947 TI - Identification of Circadian Determinants of Cancer Chronotherapy through In Vitro Chronopharmacology and Mathematical Modeling. AB - Cancer chronotherapy aims at enhancing tolerability and efficacy of anticancer drugs through their delivery according to circadian clocks. However, mouse and patient data show that lifestyle, sex, genetics, drugs, and cancer can modify both host circadian clocks and metabolism pathways dynamics, and thus the optimal timing of drug administration. The mathematical modeling of chronopharmacology could indeed help moderate optimal timing according to patient-specific determinants. Here, we combine in vitro and in silico methods, in order to characterize the critical molecular pathways that drive the chronopharmacology of irinotecan, a topoisomerase I inhibitor with complex metabolism and known activity against colorectal cancer. Large transcription rhythms moderated drug bioactivation, detoxification, transport, and target in synchronized colorectal cancer cell cultures. These molecular rhythms translated into statistically significant changes in pharmacokinetics and pharmacodynamics according to in vitro circadian drug timing. The top-up of the multiple coordinated chronopharmacology pathways resulted in a four-fold difference in irinotecan induced apoptosis according to drug timing. Irinotecan cytotoxicity was directly linked to clock gene BMAL1 expression: The least apoptosis resulted from drug exposure near BMAL1 mRNA nadir (P < 0.001), whereas clock silencing through siBMAL1 exposure ablated all the chronopharmacology mechanisms. Mathematical modeling highlighted circadian bioactivation and detoxification as the most critical determinants of irinotecan chronopharmacology. In vitro-in silico systems chronopharmacology is a new powerful methodology for identifying the main mechanisms at work in order to optimize circadian drug delivery. PMID- 26141948 TI - LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1 Dependent Mechanisms. AB - CHK1 is a multifunctional protein kinase integral to both the cellular response to DNA damage and control of the number of active replication forks. CHK1 inhibitors are currently under investigation as chemopotentiating agents due to CHK1's role in establishing DNA damage checkpoints in the cell cycle. Here, we describe the characterization of a novel CHK1 inhibitor, LY2606368, which as a single agent causes double-stranded DNA breakage while simultaneously removing the protection of the DNA damage checkpoints. The action of LY2606368 is dependent upon inhibition of CHK1 and the corresponding increase in CDC25A activation of CDK2, which increases the number of replication forks while reducing their stability. Treatment of cells with LY2606368 results in the rapid appearance of TUNEL and pH2AX-positive double-stranded DNA breaks in the S-phase cell population. Loss of the CHK1-dependent DNA damage checkpoints permits cells with damaged DNA to proceed into early mitosis and die. The majority of treated mitotic nuclei consist of extensively fragmented chromosomes. Inhibition of apoptosis by the caspase inhibitor Z-VAD-FMK had no effect on chromosome fragmentation, indicating that LY2606368 causes replication catastrophe. Changes in the ratio of RPA2 to phosphorylated H2AX following LY2606368 treatment further support replication catastrophe as the mechanism of DNA damage. LY2606368 shows similar activity in xenograft tumor models, which results in significant tumor growth inhibition. LY2606368 is a potent representative of a novel class of drugs for the treatment of cancer that acts through replication catastrophe. PMID- 26141949 TI - CDK1-Mediated SIRT3 Activation Enhances Mitochondrial Function and Tumor Radioresistance. AB - Tumor adaptive resistance to therapeutic radiation remains a barrier for further improvement of local cancer control. SIRT3, a member of the sirtuin family of NAD(+)-dependent protein deacetylases in mitochondria, promotes metabolic homeostasis through regulation of mitochondrial protein deacetylation and plays a key role in prevention of cell aging. Here, we demonstrate that SIRT3 expression is induced in an array of radiation-treated human tumor cells and their corresponding xenograft tumors, including colon cancer HCT-116, glioblastoma U87, and breast cancer MDA-MB231 cells. SIRT3 transcriptional activation is due to SIRT3 promoter activation controlled by the stress transcription factor NF kappaB. Posttranscriptionally, SIRT3 enzymatic activity is further enhanced via Thr150/Ser159 phosphorylation by cyclin B1-CDK1, which is also induced by radiation and relocated to mitochondria together with SIRT3. Cells expressing Thr150Ala/Ser159Ala-mutant SIRT3 show a reduction in mitochondrial protein lysine deacetylation, Deltapsim, MnSOD activity, and mitochondrial ATP generation. The clonogenicity of Thr150Ala/Ser159Ala-mutant transfectants is lower and significantly decreased under radiation. Tumors harboring Thr150Ala/Ser159Ala mutant SIRT3 show inhibited growth and increased sensitivity to in vivo local irradiation. These results demonstrate that enhanced SIRT3 transcription and posttranslational modifications in mitochondria contribute to adaptive radioresistance in tumor cells. CDK1-mediated SIRT3 phosphorylation is a potential effective target to sensitize tumor cells to radiotherapy. PMID- 26141950 TI - STAT1 Activation Is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells. AB - Cisplatin is a cytotoxic chemotherapeutic drug frequently used to treat many solid tumors, including head and neck squamous cell carcinoma (HNSCC). EGF receptor (EGFR) inhibitors have also shown efficacy as alternatives to cisplatin in some situations. However, large clinical trials have shown no added survival benefit from the use of these two drugs in combination. Possible explanations for this include overlapping downstream signaling cascades. Using in vitro studies, we tested the hypothesis that cisplatin and EGFR inhibitors rely on the activation of the tumor suppressor STAT1, characterized by its phosphorylation at serine (S727) or tyrosine (Y701) residues. Cisplatin consistently increased the levels of p-S727-STAT1, and STAT1 siRNA knockdown attenuated cisplatin-induced cell death. EGFR stimulation also activated p-S727-STAT1 and p-Y701-STAT1 in a subset of cell lines, whereas EGFR inhibitors alone decreased levels of p-S727 STAT1 and p-Y701-STAT1 in these cells. Contrary to our hypothesis, EGFR inhibitors added to cisplatin treatment caused variable effects among cell lines, with attenuation of p-S727-STAT1 and enhancement of cisplatin-induced cell death in some cells and minimal effect in other cells. Using HNSCC tumor specimens from a clinical trial of adjuvant cisplatin plus the anti-EGFR antibody panitumumab, higher intratumoral p-S727-STAT1 appeared to correlate with worse survival. Together, these results suggest that cisplatin-induced cell death is associated with STAT1 phosphorylation, and the addition of anti-EGFR therapy to cisplatin has variable effects on STAT1 and cell death in HNSCC. PMID- 26141951 TI - Disability Pensions Among Young Adults in Vocational Rehabilitation. AB - OBJECTIVES: Lack of work-participation and early disability pensions (DP's) among young adults are increasing public health problems in most western European countries. The present study investigated determinants of early DP in young adults in vocational rehabilitation. METHODS: Data from 928 young adults (aged 18 40 years) attending a vocational rehabilitation program was linked to DP's recorded in the Norwegian Labor and Welfare Organization registries (1992-2010) and later compared to a group of 65 employees (workers). We used logistic regression to estimate the odds ratio for entitlement to DP following rehabilitation, adjusting for socio-demographical, psychosocial and health behavior factors. RESULTS: Significant differences in socio-demographical, psychosocial and health-behavior factors were found between the rehabilitation group and workers. A total of 60 individuals (6.5%) were granted a DP during follow-up. Increase in age, teenage parenthood, single status, as well as low education level and not being employed were found to be the strongest independent determinants of DP. CONCLUSION: Poor social relations (being lone), early childbearing and weak connection to working life contributed to increase in risk of DP's among young adults in vocational rehabilitation, also after adjusting for education level. These findings are important in the prevention of early disability retirements among young adults and should be considered in the development of targeted interventions aimed at individuals particularly at risk of not being integrated into future work lives. PMID- 26141952 TI - Fatal hemorrhage following sacroiliac joint fusion surgery: A case report. AB - Threaded pins and wires are commonly used in orthopedic practice and their migration intra- or post-operatively may be responsible for potentially serious complications. Vascular and visceral injury from intra-pelvic pin or guide-wire migration during or following hip surgery has been reported frequently in the literature and may result in progression through soft tissues with subsequent perforation of organs and vessels. In this report, we describe an autopsy case involving a 40-year old man suffering from chronic low back pain due to sacroiliac joint disruption. The patient underwent minimally invasive sacroiliac joint arthrodesis. Some intra-operative bleeding was noticed when a drill was retrieved, though the patient died postoperatively. Postmortem investigations allowed the source of bleeding to be identified (a perforation of a branch of the right internal iliac artery) and a potentially toxic tramadol concentration in peripheral blood to be measured. PMID- 26141953 TI - Three Simple Strategies for Effective Leadership. PMID- 26141954 TI - Clip-assisted biliary cannulation to expose papilla covered by lipoma. PMID- 26141955 TI - Endoscopic retrieval of a proximally migrated biliary stent after pancreaticoduodenectomy by use of a short-type single-balloon enteroscope. PMID- 26141956 TI - Lineage-associated tracts defining the anatomy of the Drosophila first instar larval brain. AB - Fixed lineages derived from unique, genetically specified neuroblasts form the anatomical building blocks of the Drosophila brain. Neurons belonging to the same lineage project their axons in a common tract, which is labeled by neuronal markers. In this paper, we present a detailed atlas of the lineage-associated tracts forming the brain of the early Drosophila larva, based on the use of global markers (anti-Neuroglian, anti-Neurotactin, inscuteable-Gal4>UAS-chRFP Tub) and lineage-specific reporters. We describe 68 discrete fiber bundles that contain axons of one lineage or pairs/small sets of adjacent lineages. Bundles enter the neuropil at invariant locations, the lineage tract entry portals. Within the neuropil, these fiber bundles form larger fascicles that can be classified, by their main orientation, into longitudinal, transverse, and vertical (ascending/descending) fascicles. We present 3D digital models of lineage tract entry portals and neuropil fascicles, set into relationship to commonly used, easily recognizable reference structures such as the mushroom body, the antennal lobe, the optic lobe, and the Fasciclin II-positive fiber bundles that connect the brain and ventral nerve cord. Correspondences and differences between early larval tract anatomy and the previously described late larval and adult lineage patterns are highlighted. Our L1 neuro-anatomical atlas of lineages constitutes an essential step towards following morphologically defined lineages to the neuroblasts of the early embryo, which will ultimately make it possible to link the structure and connectivity of a lineage to the expression of genes in the particular neuroblast that gives rise to that lineage. Furthermore, the L1 atlas will be important for a host of ongoing work that attempts to reconstruct neuronal connectivity at the level of resolution of single neurons and their synapses. PMID- 26141958 TI - Meta-Analyses of Statin Therapy for Primary Prevention Do Not Answer Key Questions: An Empirical Appraisal of 5 Years of Statin Meta-Analyses. AB - Although meta-analyses of statins in primary prevention are designed to provide doctors and patients with better evidence about the risks and potential benefits of treatment, they may ignore important patient-centered outcomes and concerns. We examined all meta-analyses of statins for primary prevention over the last 5 years. We assessed whether each meta-analysis addressed five key points: whether authors examined endpoints based on the use of statin therapy, and not stratified by low-density lipoprotein reduction; whether authors included only studies of statin versus placebo, and not varying doses or brands of statin; whether authors considered commonly cited harms; whether secondary prevention patients were excluded; and, whether overall mortality was examined. We examined 189 articles to identify 24 meta-analyses of statins that made claims regarding primary prevention. Six studies (25%) reported outcomes as a function of reduction in serum lipid levels rather than treatment received. Seven studies (29%) included trials of high-dose versus low-dose statin in their analysis. Five studies (21%) did not examine all-cause mortality. The majority of studies (n = 21, 88%) failed to exclude patients with known cardiovascular disease, and 22 (92%) studies failed to assess two of three common safety concerns. Nevertheless, most (n = 20, 83%) meta-analyses supported the use of statins in primary prevention. Based on our findings, we conclude that most recent meta-analyses of statins for primary prevention do not adequately address the question they seek to answer. PMID- 26141957 TI - Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis. AB - The sequence of events that leads to the formation of a functionally graded enthesis is not clearly defined. The current study demonstrates that clonal expansion of Gdf5 progenitors contributes to linear growth of the enthesis. Prior to mineralization, Col1+ cells in the enthesis appose Col2+ cells of the underlying primary cartilage. At the onset of enthesis mineralization, cells at the base of the enthesis express alkaline phosphatase, Indian hedgehog, and ColX as they mineralize. The mineralization front then extends towards the tendon midsubstance as cells above the front become encapsulated in mineralized fibrocartilage over time. The hedgehog (Hh) pathway regulates this process, as Hh responsive Gli1+ cells within the developing enthesis mature from unmineralized to mineralized fibrochondrocytes in response to activated signaling. Hh signaling is required for mineralization, as tissue-specific deletion of its obligate transducer Smoothened in the developing tendon and enthesis cells leads to significant reductions in the apposition of mineralized fibrocartilage. Together, these findings provide a spatiotemporal map of events - from expansion of the embryonic progenitor pool to synthesis of the collagen template and finally mineralization of this template - that leads to the formation of the mature zonal enthesis. These results can inform future tendon-to-bone repair strategies to create a mechanically functional enthesis in which tendon collagen fibers are anchored to bone through mineralized fibrocartilage. PMID- 26141960 TI - Application of comparative biology in GO functional annotation: the mouse model. AB - The Gene Ontology (GO) is an important component of modern biological knowledge representation with great utility for computational analysis of genomic and genetic data. The Gene Ontology Consortium (GOC) consists of a large team of contributors including curation teams from most model organism database groups as well as curation teams focused on representation of data relevant to specific human diseases. Key to the generation of consistent and comprehensive annotations is the development and use of shared standards and measures of curation quality. The GOC engages all contributors to work to a defined standard of curation that is presented here in the context of annotation of genes in the laboratory mouse. Comprehensive understanding of the origin, epistemology, and coverage of GO annotations is essential for most effective use of GO resources. Here the application of comparative approaches to capturing functional data in the mouse system is described. PMID- 26141959 TI - Chromosomal copy number variation reveals differential levels of genomic plasticity in distinct Trypanosoma cruzi strains. AB - BACKGROUND: Trypanosoma cruzi, the etiologic agent of Chagas disease, is currently divided into six discrete typing units (DTUs), named TcI-TcVI. CL Brener, the reference strain of the T. cruzi genome project, is a hybrid with a genome assembled into 41 putative chromosomes. Gene copy number variation (CNV) is well documented as an important mechanism to enhance gene expression and variability in T. cruzi. Chromosomal CNV (CCNV) is another level of gene CNV in which whole blocks of genes are expanded simultaneously. Although the T. cruzi karyotype is not well defined, several studies have demonstrated a significant variation in the size and content of chromosomes between different T. cruzi strains. Despite these studies, the extent of diversity in CCNV among T. cruzi strains based on a read depth coverage analysis has not been determined. RESULTS: We identify the CCNV in T. cruzi strains from the TcI, TcII and TcIII DTUs, by analyzing the depth coverage of short reads from these strains using the 41 CL Brener chromosomes as reference. This study led to the identification of a broader extent of CCNV in T. cruzi than was previously speculated. The TcI DTU strains have very few aneuploidies, while the strains from TcII and TcIII DTUs present a high degree of chromosomal expansions. Chromosome 31, which is the only chromosome that is supernumerary in all six T. cruzi samples evaluated in this study, is enriched with genes related to glycosylation pathways, highlighting the importance of glycosylation to parasite survival. CONCLUSIONS: Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression, which represents a strategy that may be crucial for parasites that mainly depend on post-transcriptional mechanisms to control gene expression. PMID- 26141961 TI - Systemically-Based Psychotherapeutic Techniques in Genetic Counseling. AB - The uses of systemically-based psychotherapeutic methods in genetic counseling are discussed in the context of the origin of genetic counseling, the definition of genetic counseling, and the adjustments that one must make in order to implement these methods. Selected systemic methods which can be readily incorporated into genetic counseling are presented: use of genograms to explore family attitudes and beliefs about genetic risk, communications skills, and applications of family of origin work in genetic counseling. The need for research regarding the methodology and process of genetic counseling is presented with discussion of the need for theories of practice for genetic counseling. PMID- 26141962 TI - Family Communication and Genetic Counseling: The Case of Hereditary Breast and Ovarian Cancer. AB - In familial breast/ovarian cancer, the information that the proband is able to supply about other family members is of critical importance for genetic counseling. This frequently requires family communication. Forty-six women attending a cancer genetics clinic were interviewed as part of a longitudinal study. Nearly all reported affected maternal, rather than paternal relatives, which may indicate lack of awareness by women with paternal histories. There was also much more communication among female relatives. Mothers, where they were still alive, were key figures in supplying family information. Although the majority of the sample contacted at least one relative regarding counseling, most named a relative with whom they did not feel able to communicate on this subject. Probands balanced the perceived obligation of passing on information with that of not causing alarm. Communication, both obtaining and giving information, was impeded by adoption, divorce and remarriage, family rifts, and large age gaps between siblings. PMID- 26141963 TI - The First Prenatal Diagnosis of a Fetal Abnormality. PMID- 26141964 TI - Genetic Library. PMID- 26141965 TI - Borderline ankle-brachial index is associated with increased prevalence of micro- and macrovascular complications in type 2 diabetes: A cross-sectional analysis of 12,772 patients from the Joint Asia Diabetes Evaluation Program. AB - Borderline ankle-brachial index is increasingly recognised as a marker of cardiovascular risk. We evaluated the impact of borderline ankle-brachial index in 12,772 Chinese type 2 diabetes patients from the Joint Asia Diabetes Evaluation Program between 2007 and 2012. Cardiovascular risk factors, complications and health-related quality of life were compared between patients with normal ankle-brachial index (1.0-1.4), borderline ankle-brachial index (0.90 0.99) and peripheral arterial disease (ankle-brachial index < 0.9). The prevalence of peripheral arterial disease and borderline ankle-brachial index was 4.6% and 9.6%, respectively. Borderline ankle-brachial index patients were older, more likely to be smokers and hypertensive, had longer duration of diabetes, poorer kidney function and poorer health-related quality of life than patients with normal ankle-brachial index. After adjustment for traditional cardiovascular risk factors, borderline ankle-brachial index was an independent predictor of diabetes-related micro- and macrovascular complications including retinopathy (odd ratios: 1.19 (95% confidence interval: 1.04-1.37)), macroalbuminuria (1.31 (1.10-1.56)), chronic kidney disease (1.22 (1.00-1.50)) and stroke (1.31 (1.05 1.64)). These findings suggest that patients with diabetes and borderline ankle brachial index are at increased cardiovascular risk and may benefit from more intensive management. PMID- 26141966 TI - The associations between increasing degrees of homeostatic model assessment for insulin resistance and muscular strengthening activities among euglycaemic US adults. AB - PURPOSE: To examine the associations between the homeostatic model assessment for insulin resistance and self-reported muscular strengthening activity in a nationally representative sample of euglycaemic US adults. METHODS: Sample included euglycaemic adults (?20 years of age (n = 2009)) from the 1999 to 2004 National Health and Nutrition Examination Survey. Homeostatic model assessment for insulin resistance was categorized into quartiles and was the primary independent variable of interest. No reported muscular strengthening activity was the dependent variable. RESULTS: Following adjustment for covariates, those with homeostatic model assessment for insulin resistance values in fourth (odds ratio: 2.04, 95% confidence interval: 1.35-3.06, p < 0.001) quartile were found to have significantly greater odds of reporting no muscular strengthening activity. Following further adjustment for non-muscular strengthening activity specific aerobic leisure-time physical activity, results remained significant for the fourth (odds ratio: 2.30, 95% confidence interval: 1.50-3.52, p < 0.001) quartile. A significant trend was seen across quartiles of homeostatic model assessment for insulin resistance for increasing prevalence of no muscular strengthening activity (p < 0.001). CONCLUSION: Having a higher homeostatic model assessment for insulin resistance value is associated with greater odds of reporting no muscular strengthening activity among euglycaemic US adults. This implies that subjects with an increasing degree of insulin resistance are more likely to not engage in muscular strengthening activity, an exercise modality that has been shown to reduce the risk of several cardiometabolic diseases and improve glycaemic status. PMID- 26141967 TI - Travelling Waves of Cell Differentiation. AB - The paper is devoted to modelling of cell differentiation in an initially homogeneous cell population. The mechanism which provides coexistence of two cell lineages in the initially homogeneous cell population is suggested. If cell differentiation is initiated locally in space in the population of undifferentiated cells, it can propagate as a travelling wave converting undifferentiated cells into differentiated ones. We suggest a model of this process which takes into account intracellular regulation, extracellular regulation and different cell types. They include undifferentiated cells and two types of differentiated cells. When a cell differentiates, its choice between two types of differentiated cells is determined by the concentrations of intracellular proteins. Differentiated cells can either stimulate differentiation into their own cell lineage or into another cell lineage. In the case of the positive feedback, only one lineage of differentiated cells will finally appear. In the case of negative feedback, both of them can coexist. In this case a periodic spatial pattern emerges behind the wave. PMID- 26141968 TI - Towards a behavioral-matching based compilation of synthetic biology functions. AB - The field of synthetic biology is looking forward engineering framework for safely designing reliable de-novo biological functions. In this undertaking, Computer-Aided-Design (CAD) environments should play a central role for facilitating the design. Although, CAD environment is widely used to engineer artificial systems the application in synthetic biology is still in its infancy. In this article we address the problem of the design of a high level language which at the core of CAD environment. More specifically the Gubs (Genomic Unified Behavioural Specification) language is a specification language used to describe the observations of the expected behaviour. The compiler appropriately selects components such that the observation of the synthetic biological function resulting to their assembly complies to the programmed behaviour. PMID- 26141969 TI - The Trans-Gompertz Function: An Alternative to the Logistic Growth Function with Faster Growth. AB - The growth characteristics of the recently derived Trans-Gompertz function are compared to those of the Generalized Logistic function. Both functions are defined by one shaping parameter and one rate parameter. The functions are matched at a specified point on the growth curve by equating both the first and second derivatives. Analysis shows that the matched Trans-Gompertz function will have grown at a faster rate with a larger inflection point ratio. PMID- 26141970 TI - Achieving successful evidence-based practice implementation in juvenile justice: The importance of diagnostic and evaluative capacity. AB - Evidence-based programs (EBPs) are an increasingly visible aspect of the treatment landscape in juvenile justice. Research demonstrates that such programs yield positive returns on investment and are replacing more expensive, less effective options. However, programs are unlikely to produce expected benefits when they are not well-matched to community needs, not sustained and do not reach sufficient reach and scale. We argue that achieving these benchmarks for successful implementation will require states and county governments to invest in data-driven decision infrastructure in order to respond in a rigorous and flexible way to shifting political and funding climates. We conceptualize this infrastructure as diagnostic capacity and evaluative capacity: Diagnostic capacity is defined as the process of selecting appropriate programing and evaluative capacity is defined as the ability to monitor and evaluate progress. Policy analyses of Washington State, Pennsylvania and Louisiana's program implementation successes are used to illustrate the benefits of diagnostic and evaluate capacity as a critical element of EBP implementation. PMID- 26141971 TI - Complex Genetic Disorders: Evaluating When Genetic Research Findings Are Applicable for Genetic Counseling Practice. AB - Traditional genetic counseling processes and principles will be extended to a new realm-complex disorders. Although it may seem like a daunting task, understanding the methodologies used to study complex genetic disorders will enable genetic counselors to critically analyze research studies involving complex disorders. In this article, we explain newly evolving methodologies for genetic research, including case-control studies and transmission disequilibrium testing (TDT). Additionally, a framework is provided for evaluating original research findings and replication studies. PMID- 26141972 TI - Recurrent Trisomies: Chance or Inherited Predisposition? AB - Two patients experiencing recurring trisomic pregnancies involving a different chromosome each time are presented. Mechanisms to explain recurrent trisomies include a gene or genes predisposing to nondisjunction in general or to nondisjunction of the acrocentric chromosomes, maternal age effects, and germ line mosaicism. Genetic counseling is complicated by the lack of a clear explanation for the recurrences, difficulty in quoting a specific recurrence risk, concern regarding the risk for uniparental disomy, and the frustration, grief and guilt reactions of the patients. PMID- 26141973 TI - Genetic Library. PMID- 26141974 TI - Plantagiolides K-N, three new withanolides and one withanolide glucoside from Tacca plantaginea. AB - Phytochemical investigation of the whole plants of Tacca plantaginea led to the isolation of 3 new withanolides and one new withanolide glucoside, named plantagiolides K-N (1-4), together with one known withanolide, 4 known withanolide glucosides, and 2 known taccalonolides. Their structures were elucidated by extensive spectroscopic analysis. Compound 4 is the first withanolide glycoside which the sugar moiety is attached at C-7. The effects of the some of isolates on TNFalpha-induced NF-kappaB transcriptional activity and cytotoxicity were evaluated. PMID- 26141975 TI - Using robust Bayesian network to estimate the residuals of fluoroquinolone antibiotic in soil. AB - Prediction of antibiotic pollution and its consequences is difficult, due to the uncertainties and complexities associated with multiple related factors. This article employed domain knowledge and spatial data to construct a Bayesian network (BN) model to assess fluoroquinolone antibiotic (FQs) pollution in the soil of an intensive vegetable cultivation area. The results show: (1) The relationships between FQs pollution and contributory factors: Three factors (cultivation methods, crop rotations, and chicken manure types) were consistently identified as predictors in the topological structures of three FQs, indicating their importance in FQs pollution; deduced with domain knowledge, the cultivation methods are determined by the crop rotations, which require different nutrients (derived from the manure) according to different plant biomass. (2) The performance of BN model: The integrative robust Bayesian network model achieved the highest detection probability (pd) of high-risk and receiver operating characteristic (ROC) area, since it incorporates domain knowledge and model uncertainty. Our encouraging findings have implications for the use of BN as a robust approach to assessment of FQs pollution and for informing decisions on appropriate remedial measures. PMID- 26141976 TI - Short-term arsenic exposure reduces diatom cell size in biofilm communities. AB - Arsenic (As) pollution in water has important impacts for human and ecosystem health. In freshwaters, arsenate (As(V)) can be taken up by microalgae due to its similarity with phosphate molecules, its toxicity being aggravated under phosphate depletion. An experiment combining ecological and ecotoxicological descriptors was conducted to investigate the effects of As(V) (130 MUg L(-1) over 13 days) on the structure and function of fluvial biofilm under phosphate limiting conditions. We further incorporated fish (Gambusia holbrooki) into our experimental system, expecting fish to provide more available phosphate for algae and, consequently, protecting algae against As toxicity. However, this protection role was not fully achieved. Arsenic inhibited algal growth and productivity but not bacteria. The diatom community was clearly affected showing a strong reduction in cell biovolume; selection for tolerant species, in particular Achnanthidium minutissimum; and a reduction in species richness. Our results have important implications for risk assessment, as the experimental As concentration used was lower than acute toxicity criteria established by the USEPA. PMID- 26141977 TI - Use of red mud (bauxite residue) for the retention of aqueous inorganic mercury(II). AB - The effectiveness of the oxide-rich residue from bauxite refining (red mud) to remove inorganic Hg(II) from aqueous solutions was assessed. The aspects studied comprised the kinetics of the process (t = 1 min-24 h), the effect of pH (3.5 11.5), the interacting effect between salt concentration (0.01-1 M NaNO3) and pH and the Hg(II) sorption isotherm. Hg leaching from spent red mud was evaluated using the toxicity characteristics leaching procedure (TCLP) method. The sorption of Hg(II) onto red mud was very fast, with most of Hg(II) (97.0-99.7%) being removed from 0.5-50 MUM Hg solutions in few minutes. The kinetic process was best described by Ho's pseudo-second order equation, pointing to chemisorption as the rate controlling step. Hg(II) sorption efficiency was very high (% removal between 93.9 and 99.8%) within all the studied pH range (3.5-11.5) and added Hg concentrations (5 and 50 MUM), being optimal at pH 5-8 and decreasing slightly at both lowest and highest pH. The effect of background electrolyte concentration suggests specific sorption as the main interaction mechanism between Hg(II) and red mud, but the increasing non-sorbed Hg concentrations at low and high pH for higher electrolyte concentrations also revealed the contribution of an electrostatic component to the process. The sorption isotherm showed the characteristic shape of high affinity sorbents, and it was better described by the Redlich-Peterson and Freundlich equations, which are models that assume sorbent heterogeneity and involvement of more than one mechanism. The estimated Hg(II) sorption capacity from the Langmuir equation (q m ~9 mmol/kg) was comparable to those of some inorganic commercial sorbents but lower than most bio or specifically designed sorbents. The leachability of retained Hg(II) from spent red mud (0.02, 0.25 and 2.42 mmol Hg/kg sorbed concentration) was low (0.28, 1.15 and 2.23 MUmol/kg, respectively) and accounted for 1.2, 0.5 and 0.1% of previously sorbed Hg, indicating that Hg(II) is tightly bound by red mud once sorbed. PMID- 26141978 TI - Assessment of metal toxicity and development of sediment quality guidelines using the equilibrium partitioning model for the Three Gorges Reservoir, China. AB - The impoundment of the Three Gorges Reservoir (TGR) in China influences the quality of the water supply. Surface sediment samples from the TGR mainstream and three tributaries were collected. Acid volatile sulfide (AVS), simultaneously extractable metals (SEMs), and the fraction of organic carbon (f(oc)) were used to assess the toxicity of heavy metals. Sediment quality guidelines (SQGs) were established using the equilibrium partitioning approach. The results showed that the surface sediments were found to be oxic or suboxic. AVS concentrations in sediments were relatively low, below SEM concentrations. The [SEM] - [AVS] model indicated that all sediments possibly have adverse effects on aquatic life. However, ([SEM] - [AVS])/f(oc) predicted no adverse biological effects in some areas of the Meixi and Caotang Rivers, while adverse effects to aquatic life were uncertain for the other sediments. The partitioning coefficients, water quality criteria, and residual metals in the sediments were the main factors influencing the SQGs for the TGR, while the metals bound to AVS had a negligible effect. The normalized TGR SQGs were all much higher than the existing standards except for cadmium and copper. The differences might be attributed to the approaches used for derivation of SQGs and the physical and chemical characteristics of the sediments. PMID- 26141979 TI - Quantification of Cr(VI) in soil samples from a contaminated area in northern Italy by isotope dilution mass spectrometry. AB - The aims of the work were to detect and quantify hexavalent chromium in 14 soil samples from an area in Lombardia (northern Italy) contaminated by two polluted water plumes. Cr(VI) was extracted from the solid samples by applying focused microwaves in an alkaline medium after Cr(III) complexation with EDTA. Cr(VI) was reduced to Cr(III) when previously reported extraction conditions for the analysis of certified reference materials were used, and Cr(VI) could not be reliably quantified in the soil samples. The influence of organic matter and iron contents in the samples on the reduction of Cr(VI) was subsequently studied using a new set of soil samples with different iron and organic matter concentrations. Isotope dilution mass spectrometry (IDMS) measured two different enriched stable isotopes of Cr (54 and 53) to evaluate the reduction extent of hexavalent chromium during the analytical procedure. The extraction conditions were optimized to obtain the lowest amount of Cr(VI) reduction and quantify Cr(VI) in the polluted soil samples from Lombardia. PMID- 26141981 TI - Three-Dimensional Echocardiographic En Face Views of Ventricular Septal Defects: Feasibility, Accuracy, Imaging Protocols and Reference Image Collection. AB - BACKGROUND: Ventricular septal defect (VSD) is the most common congenital cardiac anomaly. Accurate assessment is critical for planning treatment. Recent advances in three-dimensional (3D) echocardiography have improved image quality and ease of use. METHODS: The feasibility and accuracy of three specific 3D echocardiographic protocols to demonstrate en face views of VSDs were analyzed in a retrospective review of 100 consecutive patients. Sixty-four patients underwent transthoracic echocardiography and 36 transesophageal echocardiography. Types of VSDs included 34 muscular, 32 perimembranous, 18 malaligned, 11 inlet, four outlet, and one acquired. Ages ranged from 1 day to 77 years, and body weights from 3 to 92 kg. Three-dimensional echocardiographic full-volume mode with standard XYZ and adjustable plane cropping, 3D full-volume mode with iCrop, and narrow-sector live 3D protocols were compared for feasibility and accuracy to obtain a diagnostic-quality en face view of a VSD. RESULTS: The success rate for obtaining a high-quality en face image for the three protocols was 100% for full volume mode with iCrop, 97% for full-volume standard mode, and 94% for narrow sector live 3D mode. The ability of both full-volume mode with iCrop and full volume standard mode to demonstrate a VSD was slightly better than that of narrow sector live 3D mode (P < .001 for both vs narrow-sector live 3D mode). In all patients, the type, size, and location of the VSD were demonstrated accurately by two or more of the protocols. CONCLUSIONS: Three-dimensional echocardiography of VSDs is feasible and accurate in most patients using defined protocols. The protocols are described and illustrated in detail, and a reference 3D image collection is presented. PMID- 26141980 TI - Development of an algorithm to identify serious opioid toxicity in children. AB - BACKGROUND: The use of opioids is increasing in children; therefore, opioid toxicity could be a public health problem in this vulnerable population. However, we are not aware of a published algorithm to identify cases of opioid toxicity in children using administrative databases. We sought to develop an algorithm to identify them. After review of literature and de-identified computer profiles, a broad set of ICD-9 CM codes consistent with serious opioid toxicity was selected. Based on these codes, we identified 195 potential cases of opioid toxicity in children enrolled in Tennessee Medicaid. Medical records were independently reviewed by two physicians; episodes considered equivocal were reviewed by an adjudication committee. Cases were adjudicated as Group 1 (definite/probable), Group 2 (possible), or Group 3 (excluded). RESULTS: Of the 195 potential cases, 168 (86.2%) had complete records for review and 85 were confirmed cases. The overall positive predictive value (PPV) for all codes was 50.6%. The PPV for codes indicating: unintentional opioid overdose (25/31) was 80.7%; intentional opioid overdose (15/30) was 50.0%, adverse events (33/58) was 56.9%, the presence of signs or symptoms compatible with opioid toxicity (12/47) was 25.5%, and no cases were confirmed in records from the two deaths. Of the confirmed cases, 65.8% were related to therapeutic opioid use. CONCLUSION: For studies utilizing administrative claims to quantify incidence of opioid toxicity in children, our findings suggest that use of a broad set of screening codes coupled with medical record review is important to increase the completeness of case ascertainment. PMID- 26141982 TI - Pericardiectomy is Associated with Improvement in Longitudinal Displacement of Left Ventricular Free Wall Due to Increased Counterclockwise Septal-to-Lateral Rotational Displacement. AB - BACKGROUND: Pericardiectomy is an effective intervention for constrictive pericarditis. Speckle-tracking echocardiography can provide quantitative information not only about longitudinal strain (LS) but about longitudinal displacement (LD) and septal-to-lateral rotational displacement (SLRD). The aim of this study was to investigate whether pericardiectomy improves myocardial mechanics using speckle-tracking analysis. METHODS: Eighty-three patients with constrictive pericarditis who underwent echocardiography were retrospectively assessed (mean age, 58 +/- 12 years; 72 men; 50 idiopathic, 20 postoperative, four viral, three radiation, and six others) and compared with 20 healthy volunteers. LD and SLRD were measured from the apical four-chamber view and global LS from three apical views. RESULTS: LD was less in the constrictive pericarditis group compared with control subjects (P < .001). Only lateral LS was significantly less than that of control subjects (P < .001), but septal LS was similar (P = .48). In pre- and post-pericardial surgery comparisons (n = 27), values of septal and lateral LD were almost identical (mean, 13.6 +/- 4.7 vs 13.3 +/- 5.4 mm; P = .70) before pericardiectomy, but septal LD decreased (mean, 9.3 +/- 3.5 mm; P < .001) and lateral LD increased (mean, 16.8 +/- 4.7 mm; P = .0106) after the surgery, even though the difference in LS between the septal and lateral walls decreased (from 5.6 +/- 5.3% to 2.5 +/- 4.2%, P = .008). Systolic whole-heart swinging motion significantly increased to a counterclockwise direction after surgery (mean SLRD, -0.8 +/- 3.3 degrees vs 2.1 +/- 3.0 degrees ; P = .001). Although the change in SLRD after pericardiectomy was not different between patients with decreases and increases in New York Heart Association class, SLRD change was significantly greater in patients who received fewer diuretics after surgery (mean, 4.00 +/- 0.91 vs 0.27 +/- 1.47; P = .027). CONCLUSIONS: After surgical removal of the pericardium, LD of the septal and lateral walls became significantly different, and counterclockwise SLRD increased, reflecting loss of pericardial support. PMID- 26141983 TI - Does previous open renal surgery or percutaneous nephrolithotomy affect the outcomes and complications of percutaneous nephrolithotomy. AB - In this study, we aim to evaluate the effectiveness and safety of PNL in patients with a history of open renal surgery or PNL by comparing with primary patients and to compare impact of previous open renal surgery and PNL on the success and complications of subsequent PNL. Charts of patients, who underwent PNL at our institute, were analyzed retrospectively. Patients were divided into three groups according to history of renal stone surgery. Patients without history of renal surgery were enrolled into Group 1. Other patients with previous PNL and previous open surgery were categorized as Group 2 and Group 3. Preoperative characteristic, perioperative data, stone-free status, and complication rates were compared between the groups. Stone-free status was accepted as completing clearance of stone and residual fragment smaller than 4 mm. Eventually, 2070 patients were enrolled into the study. Open renal surgery and PNL had been done in 410 (Group 2) and 131 (Group 3) patients, retrospectively. The mean operation time was longer (71.3 +/- 33.5 min) in Group 2 and the mean fluoroscopy time was longer (8.6 +/- 5.0) in Group 3 but there was no statistically significant difference between the groups. Highest stone clearance was achieved in primary PNL patients (81.62%) compared to the other groups (77.10% in Group 2 and 75.61% in Group 3). Stone-free rate was not significantly different between Group 2 and Group 3. Fever, pulmonary complications, and blood transfusion requirement were not statically different between groups but angioembolization was significantly higher in Group 2. Percutaneous nephrolithotomy is a safe and effective treatment modality for patients with renal stones regardless history of previous PNL or open renal surgery. However, history of open renal surgery but not PNL significantly reduced PNL success. PMID- 26141984 TI - Excitatory effect of Neurotropin((r)) on noradrenergic neurons in rat locus coeruleus. AB - AIMS: Although the clinical use of Neurotropin(r) as an analgesic for chronic pain has been firmly established, its analgesic mechanism is still unclear. In this study, we investigate the direct effects of Neurotropin using an electrophysiological method. MAIN METHODS: Blind patch-clamp recordings were made from rat locus coeruleus (LC) and periaqueductal gray (PAG) neurons in brainstem slices of normal rats. The effects of intracerebroventricular (icv) injection of Neurotropin on nociceptive transmission were recorded from spinal substantia gelatinosa (SG) neurons in fifth lumbar spinal nerve-ligated (L5-SNL) rats using an in vivo patch-clamp method. KEY FINDINGS: Neurotropin (0.2-1.0 NU/mL) dose dependently increased the firing rate in noradrenergic LC neurons of normal rats. Under the voltage-clamp condition, Neurotropin induced an inward current in 90% of LC neurons thatwas not affected by tetrodotoxin or an injection of GDP-beta-S (G protein inhibitor) through recording pipettes. In contrast, Neurotropin had no effects on all PAG neurons tested. Using in vivo patch-clamp recordings, the icv injection of Neurotropin inhibited both frequency and amplitude of pinch-evoked excitatory postsynaptic currents of SG neurons in L5-SNL rats. These results suggest that Neurotropin directly excites the descending noradrenergic LC neurons and inhibits nociceptive transmission in the spinal dorsal horn. SIGNIFICANCE: This study is the first direct demonstration that Neurotropin activates the noradrenergic descending pain inhibitory systems, and this would reinforce the usefulness of Neurotropin in the treatment of human neuropathic pain. PMID- 26141985 TI - Isomeric effects of anti-diabetic alpha-lipoic acid with gamma-cyclodextrin. AB - AIMS: Previous studies reported the anti-diabetic effects of alpha-lipoic acid (alphaLA) isomers: racemic-alphaLA, R-alphaLA, or S-alphaLA. Previously, we examined the anti-diabetic effects of alphaLA administered as a food additive, but were unable to demonstrate the differences among different isomers. In this study, alphaLAs were complexed with gamma-cyclodextrin (gammaCD) for the stability.We then investigated the anti-diabetic effects of racemic-, R-, and S alphaLA/gammaCDs in KKAy mice. MAIN METHODS: Male type 2 diabetic KKAy mice were divided into 5 groups, and fed either a high-fat-diet (HFD),HFD supplemented with gammaCD, or HFD supplemented with racemic-alphaLA/gammaCD, R-alphaLA/gammaCD, or S-alphaLA/gammaCD for 4 weeks. At the end of the feeding period, HbA1c and adiponectin levels were measured, PPARgamma2mRNA expression levels were assessed in adipose tissues using real-time PCR, and AMP-activated protein kinase (AMPK) phosphorylation levels were evaluated in the liver by Western blotting. KEY FINDINGS: The anti-diabetic effects of alphaLA; the isomeric compounds racemic-, R-, and S-alphaLA/gammaCD were investigated using amale type 2 diabetic KKAy mousemodel. Significant differences were observed in HbA1c and plasma adiponectin levels between R-alphaLA/gammaCD-treated mice and control mice. PPARgamma2 mRNA expression levels were slightly higher in racemic- and R-alphaLA/gammaCD-treated mice. Moreover, AMPK phosphorylation levels were elevated in racemic alphaLA/gammaCD- and R-alphaLA/gammaCD-treated mice, but remained unchanged in S alphaLA/gammaCD-treated mice. SIGNIFICANCE: These results suggested that the stereoisomerism mediates a difference in the anti-diabetic effects of racemic-, R , and S-alphaLA/gammaCDs. Furthermore, the anti-diabetic mechanism of alphaLA/gammaCD action may be attributed to the activation of AMPK in the liver. PMID- 26141986 TI - MiR-449c inhibits gastric carcinoma growth. AB - AIMS: Gastric carcinoma (GC) is among the leading causes of cancer-related deaths in China. Growing evidence indicates that dysregulation of miRNAs contributes to GC development. Although it has been shown that miR-449c acts as a tumor suppressor in lung cancer, the role of miR-449c in GC remains unclear. MAIN METHODS: Here, we analyzed miR-449c levels in GC tissues and cell lines by RT qPCR. We also overexpressed and inhibited miR-449c by transfecting miRNA mimics and antisense oligonucleotides (ASO), respectively. Cell growth was analyzed by MTT assay, and cell apoptosis was evaluated by FACS analysis. MiR-449c target genes were predicted using bioinformatics algorithms and confirmed by a dual luciferase reporter assay. KEY FINDINGS: We detected lower miR-449c levels in GC tissues; the low miR-449c levels correlated with low survival rate. Overexpression of miR-449c inhibited cell growth and promoted apoptosis, while depletion of miR-449c increased cell growth and suppressed apoptosis. Moreover, the 3' UTR of MET, an oncogene that activates tumor cell growth, appeared to be targeted by miR-449c. SIGNIFICANCE: Together, we showed that the reduced miR-449c levels in GC tissues promote GC growth, which possibly contributes to the low survival rate of GC patients. Mechanistically, miR-449c may target MET to suppress GC cell growth. PMID- 26141988 TI - Fluorescent kapakahines serve as non-toxic probes for live cell Golgi imaging. AB - AIMS: There is an ongoing need for fluorescent probes that specifically-target select organelles within mammalian cells. This study describes the development of probes for the selective labeling of the Golgi apparatus and offers applications for live cell and fixed cell imaging. MAIN METHODS: The kapakahines, characterized by a common C(3)-N(1') dimeric tryptophan linkage, comprise a unique family of bioactive marine depsipeptide natural products. We describe the uptake and subcellular localization of fluorescently-labeled analogs of kapakahine E. Using confocal microscopy, we identify a rapid and selective localization within the Golgi apparatus. Comparison with commercial Golgi stains indicates a unique localization pattern, which differs from currently available materials, therein offering a new tool to monitor the Golgi in live cells without toxic side effects. KEY FINDINGS: This study identifies a fluorescent analog of kapakahine E that is rapidly uptaken in cells and localizes within the Golgi apparatus. SIGNIFICANCE: The advance of microscopic methods is reliant on the parallel discovery of next generation molecular probes. This study describes the advance of stable and viable probe for staining the Golgi apparatus. PMID- 26141987 TI - Branched-chain amino acids ameliorate heart failure with cardiac cachexia in rats. AB - AIMS: Heart failure (HF) is associated with changes in energy metabolism of the heart, as well as in extra-cardiac organs such as the skeletal muscles. Cardiac cachexia is a common complication and is associated with poor prognosis. Branched chain amino acids (BCAAs) reportedly improve sarcopenia and cancer cachexia. We tested the hypothesis that BCAA ameliorates HF with cardiac cachexia. MAIN METHODS: We used Dahl salt-sensitive (DS) rats fed a high-salt diet as a model of HF. DS rats fed a low-salt diet were used as a control. BCAA were administered in drinking water from 11weeks of age, when cardiac hypertrophy was established but the cardiac function was preserved. Survival and the cardiac function were monitored, and animals were sacrificed at 21weeks of age and analyzed. KEY FINDINGS: In HF rats, BCAA treatment decreased the heart rate, preserved the cardiac function, and prolonged survival. BCAA also prevented body weight loss, associated with preservation of the skeletal muscle weight. Moreover, gene expression related to mitochondrial biogenesis and function was increased with BCAA in skeletal muscles. SIGNIFICANCE: BCAA preserved the body weight and cardiac function and prolonged survival in HF rats. The expression of genes involved in mitochondrial biogenesis and function in skeletal muscles was increased by BCAA. PMID- 26141989 TI - Testicular immunohistochemical and Ultrastructural changes associated with chronic cholestasis in rats: Effect of ursodeoxycholic acid. AB - AIMS: Testicular atrophy has been commonly reported in patients with chronic liver diseases. Ursodeoxycholic acid is the most widely used drug for the treatment of many liver diseases. However, its effect on testicular ultrastructure associated with chronic cholestasis has never been studied. Thus, this study aimed to assess how chronic obstructive jaundice affects the testicular ultrastructure and whether it affects the androgen receptor or the proliferating cell nuclear antigen. The role of ursodeoxycholic acid was also investigated. MAIN METHODS: Cholestasis was induced by bile duct ligation. Samples were collected 4weeks postoperative. Testicular changes were assessed using immunohistochemistry and transmission electron microscopy. KEY FINDINGS: Chronic cholestasis resulted in testicular atrophy evidenced by shrinkage and deformation of seminiferous tubules, thickening of peritubular boundaries, vacuolation, disorganization of germ cells, and maturation arrest. This was accompanied by decreased immunoreactivity of androgen receptors and proliferating cell nuclear antigen. Administration of ursodeoxycholic acid improved the testicular morphology and reversed cholestasis-induced immunohistochemical and ultrastructural changes. SIGNIFICANCE: Ursodeoxycholic acid can improve the testicular ultrastructure and restore the spermatogenic process in rats with chronic cholestasis. These findings support the clinical application of ursodeoxycholic acid in cholestatic patients especially those with hypogonadism. PMID- 26141991 TI - Experimental evidence of MAP kinase gene expression on the response of intestinal anti-inflammatory drugs. AB - AIM: The etiopathogenesis of inflammatory bowel disease (IBD) is unclear and further understanding of the mechanisms that regulate intestinal barrier integrity and function could give insight into its pathophysiology and mode of action of current drugs used to treat human IBD. Therefore, we investigated how intestinal inflammation affects Map kinase gene expression in rats, and if current intestinal anti-inflammatory drugs (sulphasalazine, prednisolone and azathioprine) act on these expressions. MATERIAL AND METHODS: Macroscopic parameters of lesion, biochemical markers (myeloperoxidase, alkaline phosphatase and glutathione), gene expression of 13Map kinases, and histologic evaluations (optic, electronic scanning and transmission microscopy) were performed in rats with colonic inflammation induced by trinitrobenzenesulphonic (TNBS) acid. KEY FINDINGS: The colonic inflammation was characterized by a significant increase in the expression of Mapk1, Mapk3 and Mapk9 accompanied by a significant reduction in the expression ofMapk6. Alterations inMapk expression induced by TNBS were differentially counteracted after treatment with sulphasalazine, prednisolone and azathioprine. Protective effects were also related to the significant reduction of oxidative stress, which was related to increase Mapk1/3 expressions, which were reduced after pharmacological treatment. SIGNIFICANCE: Mapk1, Mapk3,Mapk6 and Mapk9 gene expressionswere affected by colonic inflammation induced by TNBS in rats and counteracted by sulphasalazine, prednisolone and azathioprine treatments, suggesting that these genes participate in the pharmacological response produced for these drugs. PMID- 26141990 TI - Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1alpha signaling. AB - AIMS: Hypoxia is implicated in the pathogenesis of rheumatoid arthritis (RA), contributing to the tumor-like phenotypes of RA fibroblast-like synoviocytes (RA FLSs). Andrographolide is the main bioactive component of Andrographis paniculata, an herbal medicine that shows therapeutic benefits in RA patients. Here, we explored the effects of andrographolide on hypoxia-induced migration and invasion of RA-FLSs. MATERIALS AND METHODS: RA-FLSs were exposed to hypoxia in the presence or absence of andrographolide and cell migration and invasion were tested by Transwell assays. The expression of hypoxia-inducible factor-1 alpha (HIF-1alpha), matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9 was measured by semi-quantitative reverse transcription polymerase chain reaction and Western blot analysis. HIF-1alpha DNA binding activity was assessed by electrophoretic mobility shift assay. The effects of overexpression of exogenous HIF-1alpha on the action of andrographolide in RA-FLSs were investigated. KEY FINDINGS: Andrographolide inhibited FLS migration and invasion under hypoxic conditions in a dose-dependent manner. The upregulation of MMP-1, MMP-3 and MMP-9 in response to hypoxia was significantly (P<0.05) attenuated by andrographolide. Moreover, the expression and DNA binding activity of HIF-1alpha were dose-dependently decreased in andrographolide-treated cells under hypoxic conditions. Overexpression of HIF-1alpha almost completely reversed the suppressive effects of andrographolide on the migration, invasion and MMP expression of hypoxic RA FLSs. SIGNIFICANCE: These results indicate the ability of andrographolide to attenuate hypoxia-induced invasiveness of RA-FLSs via inhibition of HIF-1alpha signaling, and warrant further exploration of andrographolide for the treatment of RA. PMID- 26141992 TI - Biochanin A inhibits lipopolysaccharide-induced inflammation in human umbilical vein endothelial cells. AB - AIM: Biochanin A, an isoflavone isolated from red clover, cabbage or alfalfa, has been reported to have anti-inflammatory activity. However, the effects of biochanin A on vascular inflammation have not been investigated. In this study, we investigate the anti-inflammatory effects of biochanin A on lipopolysaccharide (LPS)-induced inflammatory response in human umbilical vein endothelial cells (HUVEC cells). MAIN METHODS: The HUVEC cells were treated with biochanin A for 12h before exposure to LPS. The expression of ECAMs, including VCAM-1, ICAM-1, E selectin, NF-kappaB and PPAR-gamma was detected by Western blotting. The expression of cytokines TNF-alpha and IL-8 was detected by ELISA. KEY FINDINGS: The results showed that biochanin A inhibited LPS-induced TNF-alpha and IL-8 production. Meanwhile, biochanin A also suppressed VCAM-1, ICAM-1, and E-selectin expression induced by LPS. We also found that biochanin A inhibited NF-kappaB activation induced by LPS. Furthermore, biochanin A could activate PPAR-gamma and the anti-inflammatory effects of biochanin A can be reversed by GW9662, a specific antagonist for PPAR-gamma. SIGNIFICANCE: In conclusion, the anti inflammatory effect of biochanin A is associated with activating PPAR-gamma, thereby attenuating NF-kappaB activation and LPS-induced inflammatory response. These findings suggest that biochanin A may be a therapeutic agent for inflammatory cardiovascular disease. PMID- 26141993 TI - Possible role of endostatin in the antiangiogenic therapy of diabetic retinopathy. AB - Diabetic retinopathy is one of various complications of diabetes mellitus, which is one of the most prevalent chronic disorders in the modern world. Diabetic retinopathy is one of the secondary complications encountered by the patients suffering from chronic diabetes mellitus. Two major characterizing features of diabetic retinopathy are - macular edema and angiogenesis. It has been noted in the past few years that by controlling or completely inhibiting the factors contributing to the progression of events leading to angiogenesis, there is a noticeable amount of progress seen in the prevention and cure of the animal models of diabetic retinopathy. Endostatin is one such antiangiogenic agent being studied at present. It is a carbon terminal protein fragment obtained after cleavage from the carbon terminus of collagen XVIII. It is one of the most potent inhibitors of angiogenesis known at present and is currently undergoing clinical trials. Although the exact mechanism of action of endostatin is not completely known, various factors which are altered/influenced by the action of endostatin are being studied. These include the downregulation and activation/inactivation of various factors which have been proven to have some role in the progression of angiogenesis. Endostatin could be well exploited as a durable agent in the antiangiogenic therapy, once the clinical trials show positive results. PMID- 26141994 TI - Spectral analysis of cooling induced hemodynamic perturbations indicates involvement of sympathetic activation and nitric oxide production in rats. AB - AIMS: Oscillations in arterial pressure and heart period in response to cold stress are poorly understood. We used a telemetric device with spectral and cross spectral analyses to assess variabilities in the heart rate (HRV) and blood pressure (BPV) of conscious rats receiving a cooling stimulus (CS) (rapid immersion of palms and soles into 4 degrees C water) at ambient thermoneutral conditions (TC), in a cold room (CC), and when under pentobarbital anesthesia (UA). MAIN METHODS: Power spectra of very low, low, and high frequencies (VLF: 0.02 to 0.2Hz, LF: 0.2 to 0.6Hz, and HF: 0.6 to 3.0Hz), dicrotic notch (Dn) and plasma nitric oxide (NO) levels were measured for statistical comparisons. KEY FINDINGS: When compared to resting rats (PreCS), CS evoked in rats the following hemodynamic perturbations: 1) pressor and tachycardia; 2) increases in VLFBPV, LFBPV, HFBPV, and TPBPV but decreases in VLFHRV, LFHRV, and TPHRV; 3) a positive correlation between LFBPV and VLFBPV but an inverse correlation between VLFHRV and VLFBPV and LFHRV and LFBPV; 4) high coherence value at frequency region of LF between BPV and HRV; and 5) increase of NO production and disappearance of Dn. Additionally, CS of CC and UA rats compared with TC rats evoked different patterns of hemodynamic perturbations; CC rats were activated but UA rats were inactivated. SIGNIFICANCE: Our findings indicate that changes in VLFBPV are related to the myogenic vascular responsiveness to CS. Power spectra changes to CS are highly relevant to sympathetic activation and NO production. PMID- 26141995 TI - A maternal high salt diet disturbs cardiac and vascular function of offspring. AB - AIMS: High salt intake is an environmental factor that promotes increased blood pressure. We previously demonstrated that high salt diet causes aggravation of hypertension and impaired vasodilation in response to nitric oxide (NO) in young spontaneously hypertensive rats (SHR), which exhibit low sensitivity to salt in adulthood. Changes in offspring blood pressure and cardiovascular structures have been reported. However, it remains unclear to what extent a maternal high salt intake may affect cardiac and/or vascular function in offspring. Therefore, we investigated influence of exposure to a maternal high salt diet during gestation and lactation on offspring's cardiac and arterial functions in SHR. MAIN METHODS: SHR dams were fed either a high salt diet or a control diet. After weaning, the offspring were fed the high salt diet or control diet for 8weeks. KEY FINDINGS: Compared with offspring of control diet-fed dams, at 12weeks of age, offspring of the high-salt diet-fed dams had lower blood pressure, heart rate, indices of both left ventricular systolic and diastolic function, and a decreased aortic vasodilation response to NO. Postnatal high salt intake did not affect blood pressure, vasodilatory response, or cardiac function in offspring of high-salt diet-fed dams. Neither maternal nor postnatal dietary salt altered levels of lipid peroxide, superoxide dismutase, or angiotensinogen mRNA in serum and ventricle of the offspring. SIGNIFICANCE: Exposure to high maternal dietary salt induces cardiac and vascular dysfunction in offspring. These results point to the possible importance of avoiding excess dietary salt during gestation and lactation. PMID- 26141996 TI - Anti-melanogenesis and antigenotoxic activities of eriodictyol in murine melanoma (B16-F10) and primary human keratinocyte cells. AB - AIMS: The objective of this study was to examine the effect of eriodictyol on melanogenesis in cultured murine melanoma cells (B16-F10) and its antigenotoxic and antioxidant potentials on primary human keratinocyte (PHK) cells. MAIN METHODS: Anti-melanogenic effect was performed via the determination of melanin content and tyrosinase activity. Antigenotoxicity and antioxidant potentials were assessed by comet and cellular antioxidant assays, respectively. KEY FINDINGS: Eriodictyol reduced melanogenesis by inhibiting the tyrosinase activity of B16 F10 cells in a dose dependent manner. Its eventual genotoxicity was investigated by evaluating its capacity to induce DNA degradation of treated cell nuclei. As no genotoxicity was detected at the different tested concentrations, its ability to protect cell DNA against hydrogen peroxide (H2O2) oxidative effect in PHK cells was investigated using the "comet assay. It appears that 50 MUM of eriodictyol solution suppressed H2O2 induced genotoxicity. In addition, this molecule revealed a significant cellular antioxidant capacity against reactive oxygen species formation in B16-F10 and PHK cells. SIGNIFICANCE: Thus, eriodictyol could be introduced as a natural skin depigmenting agent in skin care products. PMID- 26141997 TI - Potentiation of natural killer (NK) cell activity by methanol extract of cultured cambial meristematic cells of wild ginseng and its mechanism. AB - AIMS: As an alternative strategy to obtain large amounts of ginseng extract with high yield of ginsenosides, we have utilized culture of cambial meristematic cells (CMCs) from wild ginseng. The anti-tumor effects of methanol extract of ginseng CMCs (MEGC) and their action mechanisms were investigated. MAIN METHODS: Mice were intraperitoneally administered with MEGC, and we explored NK cell activity, suppression of in vivo growth of tumor cells and relevant molecule expression. KEY FINDINGS: MEGC significantly potentiated NK cell activity and suppressed in vivo growth of B16 melanoma cells. However, we observed no increase in NK cell number and unaltered expression of NK cell-activating (NKG2D) and inhibitory (Ly49, CD94/NKG2A) receptors as well as NK cell activation markers (CD25, CD69, CD119, and CD212) in MEGC-treated group compared to the controls. Instead, MEGC significantly enhanced IL-2 responsiveness in the early effector phase and the constitutive expression of granzyme B. SIGNIFICANCE: Our data indicate that culture of CMCs is an attractive alternative method for sustainable production of ginseng extracts and clinical use. In addition, we have unraveled a novel mechanism underlying the potentiation of NK cell activity and antitumor effect of ginseng extract, in which it upregulates the constitutive expression of cytotoxic mediator(s) and IL-2 responsiveness. PMID- 26141999 TI - Editorial. PMID- 26141998 TI - Nutritional profile of older adults with chronic venous leg ulcers: a pilot study. AB - The purpose of this cross-sectional descriptive pilot study was to describe daily intake of select nutrients important for efficient wound healing and general health in a sample of older adults (64.25 +/- 9.49 years of age) with chronic venous leg ulcers (CVLUs; N = 12), compared to recommended dietary allowances (RDA). Anthropometric data were also collected. Compared to RDA, participants on average consumed lower vitamin C (60.03 +/- 49.73 mg/d) and higher sodium (3197.07 +/- 1455.04 mg/d), sugar (181.21 +/- 115.45 g/d), and saturated fat (33.75 +/- 1.06 g/d). They also demonstrated a relatively high plasma n-6/n-3 polyunsaturated fatty acid ratio, a biomarker of inflammation (11.25 +/- 1.99). The mean body mass index indicated extreme obesity (41.48 +/- 11.47). A multidisciplinary treatment approach that includes routine dietary assessments followed by tailored dietary interventions may improve wound healing and long term health outcomes in this population. PMID- 26142000 TI - "People Say It's a Little Uncomfortable": Prenatal Genetic Counselors' Use of Constructed Dialogue to Reference Procedural Pain. AB - Prenatal genetic counseling involves an exchange of information between counselors and clients, including verbal descriptions of the potential pain of invasive prenatal diagnosis procedures such as amniocentesis. This paper describes the use of one linguistic feature in one context. It considers how two counselors describe procedural pain in 17 prenatal genetic counseling sessions, audiotaped as part of a larger data-driven study using sociolinguistic methodologies to characterize the discourse of genetic counseling. Analysis reveals that "constructed dialogue," or reporting something another person said, is a strategy used frequently by the counselors for describing procedural pain. Examination of the content and form of the constructed dialogue uncovered three recurring patterns that relate to its functions in the sessions: (1) inclusion of colloquial vocabulary; (2) references to common experiences through similes; and (3) explicit downplaying of pain. This analysis suggests that the naturally occurring phenomenon of quoting the words of others can be used in genetic counseling to impart information while simultaneously reassuring the client and creating counselor-client rapport. The complex relationship between the use of constructed dialogue and the enactment of genetic counseling principles through talk is also discussed. PMID- 26142001 TI - Defining Moments: Catalysts for Professional Development. AB - In this series of papers, 17 genetic counselors describe defining moments, that is, personal experiences or events that led to a further realization of themselves as genetic counselors. These experiences, both positive and negative, describe a significant impact on the authors' professional growth and development. A call for papers was issued through the National Society of Genetic Counselors listserv and through the Journal of Genetic Counseling in 2001. This call resulted in the following 15 papers in which the authors were asked to describe the nature of a defining moment and how it affected their professional identity and practice. The authors provided an account of the experience or event, what it was about the experience that made it a defining moment, how it affected them personally and professionally, and if a defining moment was negative, how they were able to derive positive outcomes. Implications of these defining moments for other genetic counselors are discussed in a concluding paper. PMID- 26142002 TI - Lifetime Continuing Education: Learning from My Son. PMID- 26142003 TI - Genetic Counseling: A New Perspective. PMID- 26142004 TI - Genetic Counselor or Patient-Who Am I Today? PMID- 26142005 TI - Compassionate Colleague, Genetic Counselor, and Friend. PMID- 26142006 TI - When Grief Roars. PMID- 26142007 TI - Pregnancy and Genetic Counseling: The Other Side of the Fence. PMID- 26142008 TI - Beach Glass. PMID- 26142009 TI - Overcoming Self-Doubt in the Genetic Counseling Session-A Student's Perspective. PMID- 26142010 TI - Defining Moments in Genetic Counseling, Or, the Day I Knew "The Patient Is Not Always Right". PMID- 26142011 TI - Defining Moments: Professional Integrity. PMID- 26142012 TI - Defining Moments: Coming Full Circle. PMID- 26142013 TI - Everything I Ever Needed to Know About Genetic Counseling Research I Learned from Attending the Jane Engelberg Memorial Fellowship Grantmanship Seminar. PMID- 26142014 TI - There Is Power in Numbers. PMID- 26142015 TI - Pushing Through the Door. PMID- 26142016 TI - A Conversation About the Indirect Road to Nondirective Genetic Counseling: A Defining Moment Through Research. PMID- 26142017 TI - Defining Moments: Important Lessons for Genetic Counselors. PMID- 26142018 TI - How does lever length and the position of its axis of rotation influence human performance during lever wheelchair propulsion? AB - The purpose of this study was to investigate empirically how lever length and its axis of rotation position influences human performance during lever wheelchair propulsion. In order to fulfill this goal, a dedicated test stand allowing easy implementation of various lever positions was created. In the experiment, 10 young, healthy, male subjects performed 8 tests consisting of propulsion work with levers of different lengths and lever axis of rotation positions. During tests heart rate, oxygen consumption and EMG assessment of 6 muscles was carried out. Measurements of power output on the test stand were done as well. Together with oxygen consumption analysis, this allowed calculation of human work efficiency. The results show significant (p<0.05 and p<0.001) differences between lever configurations when comparing various parameters values. From the carried out experiments, the authors conclude that levers' length and their axis of rotation position significantly influence human performance during lever wheelchair propulsion. For the examined subjects, placing the levers' axis of rotation close behind the back wheels axis of rotation offered advantageous work conditions. PMID- 26142019 TI - Phytomonas: A non-pathogenic trypanosomatid model for functional expression of proteins. AB - Phytomonas are protozoan parasites from the Trypanosomatidae family which infect a wide variety of plants. Herein, Phytomonas Jma was tested as a model for functional expression of heterologous proteins. Green fluorescent protein expression was evaluated in Phytomonas and compared with Trypanosoma cruzi, the etiological agent of Chagas' disease. Phytomonas was able to express GFP at levels similar to T. cruzi although the transgenic selection time was higher. It was possible to establish an efficient transfection and selection protocol for protein expression. These results demonstrate that Phytomonas can be a good model for functional expression of proteins from other trypanosomatids, presenting the advantage of being completely safe for humans. PMID- 26142021 TI - Orthodeoxia-platypnea syndrome and stroke: Overlapping pathophysiology. PMID- 26142020 TI - Performance of alternative strategies for primary cervical cancer screening in sub-Saharan Africa: systematic review and meta-analysis of diagnostic test accuracy studies. AB - OBJECTIVE: To assess and compare the accuracy of visual inspection with acetic acid (VIA), visual inspection with Lugol's iodine (VILI), and human papillomavirus (HPV) testing as alternative standalone methods for primary cervical cancer screening in sub-Saharan Africa. DESIGN: Systematic review and meta-analysis of diagnostic test accuracy studies. DATA SOURCES: Systematic searches of multiple databases including Medline, Embase, and Scopus for studies published between January 1994 and June 2014. REVIEW METHODS: Inclusion criteria for studies were: alternative methods to cytology used as a standalone test for primary screening; study population not at particular risk of cervical cancer (excluding studies focusing on HIV positive women or women with gynaecological symptoms); women screened by nurses; reference test (colposcopy and directed biopsies) performed at least in women with positive screening results. Two reviewers independently screened studies for eligibility and extracted data for inclusion, and evaluated study quality using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) checklist. Primary outcomes were absolute accuracy measures (sensitivity and specificity) of screening tests to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+). RESULTS: 15 studies of moderate quality were included (n=61,381 for VIA, n=46,435 for VILI, n=11,322 for HPV testing). Prevalence of CIN2+ did not vary by screening test and ranged from 2.3% (95% confidence interval 1.5% to 3.3%) in VILI studies to 4.9% (2.7% to 7.8%) in HPV testing studies. Positivity rates of VILI, VIA, and HPV testing were 16.5% (9.8% to 24.7%), 16.8% (11.0% to 23.6%), and 25.8% (17.4% to 35.3%), respectively. Pooled sensitivity was higher for VILI (95.1%; 90.1% to 97.7%) than VIA (82.4%; 76.3% to 87.3%) in studies where the reference test was performed in all women (P<0.001). Pooled specificity of VILI and VIA were similar (87.2% (78.1% to 92.8%) v 87.4% (77.1% to 93.4%); P=0.85). Pooled sensitivity and specificity were similar for HPV testing versus VIA (both P >= 0.23) and versus VILI (both P >= 0.16). Accuracy of VIA and VILI increased with sample size and time period. CONCLUSIONS: For primary screening of cervical cancer in sub-Saharan Africa, VILI is a simple and affordable alternative to cytology that demonstrates higher sensitivity than VIA. Implementation studies are needed to assess the effect of these screening strategies on the incidence and outcomes of cervical cancer in the region. PMID- 26142022 TI - Isolated hippocampal infarcts: Vascular and neuropsychological findings. AB - BACKGROUND AND PURPOSE: The hippocampus plays a role in the verbal and spatial memory processing, learning, and emotions. The purpose of this study was to determine clinical, etiological, and radiological features of isolated hippocampal infarcts. METHODS: We reviewed, 6800 patients with first-ever ischaemic stroke included in our Stroke Registry between 2004 and 2014. Among them we studied 19 patients with an acute isolated hippocampal infarct confirmed by MRI. RESULTS: Among 6800 patients, 19 patients (0.03%) showed ischaemic lesions in the hippocampal artery territory, allowing us to delineate 5 variant distributions; (1) anterior hippocampal infarcts (4 patients [21%]) were present with altered consciousness, transient visual vivid hallucinations, and transient global amnesia with episodic and verbal memory deficits. (2) Posterior hippocampal infarcts (3 patients [16%]) developed dizziness and dullness at stroke onset, confusion, episodic and procedural memory deficit and verbal learning deficit. (3) Unilateral complete hippocampal infarcts were present (4 patients [21%]) with confusion, object specific hallucinations, intense mood states changes as well as impulsivity or depressive behaviour. Memory dysfunctions were found in all patients. (4) Bilateral hippocampal infarcts (3 patients [16%]) had cognitive deficits and memory deficits in all patients. All patients had difficulties retrieving specific autobiographical events and retrieving recent memory, and disturbances of learning in verbal and visual task. Hippocampal dementia was observed in 2 patients with severe immediate, delayed verbal and visual memory deficits, dysexecutive syndrome, deficits in responding to feedback and error correction with dull and aimless appearance lasting several months. (5) Small circumscribed (punctiform) hippocampal infarcts (5 patients [26%]) showed dizziness or dullness sensation and difficulties finding words or objects that they use everyday. Cardioembolism (10; 53%) and large-artery disease of the vertebrobasilar system (6; 32%) were the main stroke mechanisms. CONCLUSIONS: We described topographic patterns of hippocampal infarction with distinct manifestations and etiologies. We thought that different patterns of hippocampal infarcts are the result of variation in hippocampal arterial supply or reflect a source of embolism. PMID- 26142023 TI - Coexistence of autosomal recessive spastic ataxia of Charlevoix Saguenay and spondyloepiphyseal dysplasia in a Turkish patient. PMID- 26142024 TI - Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity. AB - Neuroferritinopathy is an autosomal dominant adult-onset movement disorder which occurs due to mutations in the ferritin light chain gene (FTL). Extensive iron deposition and cavitation are observed post-mortem in the basal ganglia, but whether more widespread pathological changes occur, and whether they correlate with disease severity is unknown. 3D-T1w and quantitative T2 whole brain MRI scans were performed in 10 clinically symptomatic patients with the 460InsA FTL mutation and 10 age-matched controls. Voxel-based morphometry (VBM) and voxel based relaxometry (VBR) were subsequently performed. Clinical assessment using the Unified Dystonia Rating Scale (UDRS) and Unified Huntington's Disease Rating Scale (UHDRS) was undertaken in all patients. VBM detected significant tissue changes within the substantia nigra, midbrain and dentate together with significant cerebellar atrophy in patients (FWE, p < 0.05). Iron deposition in the caudate head and cavitation in the lateral globus pallidus correlated with UDRS score (p < 0.001). There were no differences between groups with VBR. Our data show that progressive iron accumulation in the caudate nucleus, and cavitation of the globus pallidus correlate with disease severity in neuroferritinopathy. We also confirm sub-clinical cerebellar atrophy as a feature of the disease. We suggest that VBM is an effective technique to detect regions of iron deposition and cavitation, with potential wider utility to determine radiological markers of disease severity for all NBIA disorders. PMID- 26142025 TI - Development of a new scale for dysphagia in patients with progressive neuromuscular diseases: the Neuromuscular Disease Swallowing Status Scale (NdSSS). AB - Dysphagia is one of the most critical problems in patients with progressive neuromuscular diseases. However, clinically useful and practical scales to evaluate dysphagia are limited. Therefore, the aim of this study was to develop such a scale. An 8-stage Neuromuscular Disease Swallowing Status Scale (NdSSS) was developed and tested for its inter- and intrarater reliabilities, concurrent validity, and responsiveness. The NdSSS was used to evaluate 134 patients with Duchenne muscular dystrophy (DMD) and 84 patients with amyotrophic lateral sclerosis (ALS). Inter- and intrarater reliabilities were examined with weighted kappa statistics. Concurrent validity was assessed by correlating the NdSSS with the existing scales [Functional Oral Intake Scale (FOIS), Functional Intake LEVEL Scales (FILS), and ALS Functional Rating Scale-Revised Swallow (ALSFRS-R Sw)], using Spearman's correlation coefficients. Responsiveness was determined with the standardized response mean (SRM). For inter- and intrarater reliabilities, the weighted kappas were 0.95 and 1.00, respectively, for DMD; and 0.98 and 0.98, respectively, for ALS. The NdSSS showed strong correlations with the FOIS (rs = 0.87 for DMD, rs = 0.93 for ALS, p < 0.001), FILS (rs = 0.89 for DMD, rs = 0.92 for ALS, p < 0.001), and ALSFRS-R SW (rs = 0.93, p < 0.001). SRMs were 0.65 for DMD and 1.21 for ALS. The SRM was higher in DMD patients for the NdSSS than for the other scales, while it was similar in ALS patients and the other scales. Our originally developed NdSSS demonstrated sufficient reliability, validity, and responsiveness in patients with DMD and ALS. It is also useful in evaluating dysphagia in patients with progressive neuromuscular diseases. PMID- 26142026 TI - Radiation therapy for synchronous basal cell carcinoma and lentigo maligna of the nose: Response assessment by clinical examination and reflectance confocal microscopy. PMID- 26142028 TI - Epidemiology and Risk Factors for Upper Gastrointestinal Bleeding. AB - Although the incidence of nonvariceal upper gastrointestinal bleeding (UGIB) has been decreasing worldwide, nonvariceal UGIB continues to be a significant problem. Even with the advent of advanced endoscopic procedures and potent medications to suppress acid production, UGIB carries significant morbidity and mortality. Some of the most common risk factors for nonvariceal UGIB include Helicobacter pylori infection, nonsteroidal antiinflammatory drugs (NSAIDs), aspirin, selective serotonin reuptake inhibitors, and other antiplatelet and anticoagulant medications. In patients with cardiovascular disease and kidney disease, UGIB tends to be more severe and has greater morbidity. Many of the newer NSAIDs have been removed from the market. PMID- 26142029 TI - Initial Assessment and Resuscitation in Nonvariceal Upper Gastrointestinal Bleeding. AB - Acute nonvariceal upper gastrointestinal bleeding remains an important cause of hospital admission with an associated mortality of 2-14%. Initial patient evaluation includes rapid hemodynamic assessment, large-bore intravenous catheter insertion and volume resuscitation. A hemoglobin transfusion threshold of 7 g/dL is recommended, and packed red blood cell transfusion may be necessary to restore intravascular volume and improve tissue perfusion. Patients should be risk stratified into low- and high-risk categories, using validated prognostic scoring systems such as the Glasgow-Blatchford, AIMS65 or Rockall scores. Effective early management of acute, nonvariceal upper gastrointestinal hemorrhage is critical for improving patient outcomes. PMID- 26142027 TI - Local control rates of metastatic renal cell carcinoma (RCC) to the bone using stereotactic body radiation therapy: Is RCC truly radioresistant? AB - PURPOSE: We report the radiographic and clinical response rate of stereotactic body radiation therapy (SBRT) compared with conventional fractionated external beam radiation therapy (CF-EBRT) for renal cell carcinoma (RCC) bone lesions treated at our institution. METHODS AND MATERIALS: Forty-six consecutive patients were included in the study, with 95 total lesions treated (50 SBRT, 45 CF-EBRT). We included patients who had histologic confirmation of primary RCC and radiographic evidence of metastatic bone lesions. The most common SBRT regimen used was 27 Gy in 3 fractions. RESULTS: Median follow-up was 10 months (range, 1 64 months). Median time to symptom control between SBRT and CF-EBRT were 2 (range, 0-6 weeks) and 4 weeks (range, 0-7 weeks), respectively. Symptom control rates with SBRT and CF-EBRT were significantly different (P = .020) with control rates at 10, 12, and 24 months of 74.9% versus 44.1%, 74.9% versus 39.9%, and 74.9% versus 35.7%, respectively. The median time to radiographic failure and unadjusted pain progression was 7 months in both groups. When controlling for gross tumor volume, dose per fraction, smoking, and the use of systemic therapy, biologically effective dose >=80 Gy was significant for clinical response (hazard ratio [HR], 0.204; 95% confidence interval [CI], 0.043-0.963; P = .046) and radiographic (HR, 0.075; 95% CI, 0.013-0.430; P = .004). When controlling for gross tumor volume and total dose, biologically effective dose >=80 Gy was again predictive of clinical local control (HR, 0.140; 95% CI, 0.025-0.787; P = .026). Toxicity rates were low and equivalent in both groups, with no grade 4 or 5 toxicity reported. CONCLUSIONS: SBRT is both safe and effective for treating RCC bone metastases, with rapid improvement in symptoms after treatment and more durable clinical and radiographic response rate. Future prospective trials are needed to further define efficacy and toxicity of treatment, especially in the setting of targeted agents. PMID- 26142030 TI - Nonvariceal Upper Gastrointestinal Bleeding: Timing of Endoscopy and Ways to Improve Endoscopic Visualization. AB - Upper gastrointestinal (UGI) endoscopy is the cornerstone of diagnosis and management of patients presenting with acute UGI bleeding. Once hemodynamically resuscitated, early endoscopy (performed within 24 hours of patient presentation) ensures accurate identification of the bleeding source, facilitates risk stratification based on endoscopic stigmata, and allows endotherapy to be delivered where indicated. Moreover, the preendoscopy use of a prokinetic agent (eg, i.v. erythromycin), especially in patients with a suspected high probability of having blood or clots in the stomach before undergoing endoscopy, may result in improved endoscopic visualization, a higher diagnostic yield, and less need for repeat endoscopy. PMID- 26142031 TI - Management of Antiplatelet Agents and Anticoagulants in Patients with Gastrointestinal Bleeding. AB - Antithrombotic drugs (anticoagulants, aspirin, and other antiplatelet agents) are used to treat cardiovascular disease and to prevent secondary thromboembolic events. These drugs are independently associated with an increased risk of gastrointestinal bleeding (GIB), and, when prescribed in combination, further increase the risk of adverse bleeding events. Clinical evidence to inform the choice of endoscopic hemostatic procedure, safe temporary drug cessation, and use of reversal agents is reviewed to optimize management following clinically significant GIB. PMID- 26142032 TI - Role of Medical Therapy for Nonvariceal Upper Gastrointestinal Bleeding. AB - Nonvariceal upper gastrointestinal bleeding (UGIB) is a major cause of morbidity and mortality worldwide. Mortality from UGIB has remained 5-10% over the past decade. This article presents current evidence-based recommendations for the medical management of UGIB. Preendoscopic management includes initial resuscitation, risk stratification, appropriate use of blood products, and consideration of nasogastric tube insertion, erythromycin, and proton pump inhibitor therapy. The use of postendoscopic intravenous proton pump inhibitors is strongly recommended for certain patient populations. Postendoscopic management also includes the diagnosis and treatment of Helicobacter pylori, appropriate use of proton pump inhibitors and iron replacement therapy. PMID- 26142033 TI - The Role of Medical Therapy for Variceal Bleeding. AB - Acute variceal hemorrhage (AVH) is a lethal complication of portal hypertension and should be suspected in every patient with liver cirrhosis who presents with upper gastrointestinal bleed. AVH-related mortality has decreased in the last few decades from 40% to 15%-20% due to advances in the general and specific management of variceal hemorrhage. This review summarizes current management of AVH and prevention of recurrent hemorrhage with a focus on pharmacologic therapy. PMID- 26142035 TI - Injection and Cautery Methods for Nonvariceal Bleeding Control. AB - Upper gastrointestinal bleeding remains one of the most common challenges faced by gastroenterologists and endoscopists in daily clinical practice. Endoscopic management of nonvariceal bleeding has been shown to improve clinical outcomes, with significant reduction of recurrent bleeding, need for surgery, and mortality. Early upper gastrointestinal endoscopy is recommended in all patients presenting with upper gastrointestinal bleeding within 24 hours of presentation, although appropriate resuscitation, stabilization of hemodynamic parameters, and optimization of comorbidity before endoscopy are essential. PMID- 26142036 TI - Mechanical Hemostasis Techniques in Nonvariceal Upper Gastrointestinal Bleeding. AB - One of the most important advances in gastroenterology has been the use of endoscopic hemostasis techniques to control nonvariceal upper gastrointestinal bleeding, particularly when high-risk stigmata are present. Several options are available, including injection therapy, sprays/topical agents, electrocautery, and mechanical methods. The method chosen depends on the nature of the lesion and experience of the endoscopist. This article reviews the available mechanical hemostatic modalities. PMID- 26142034 TI - Endoscopic Diagnosis and Therapy in Gastroesophageal Variceal Bleeding. AB - Gastroesophageal variceal hemorrhage is a medical emergency with high morbidity and mortality. Endoscopic therapy is the mainstay of management of bleeding varices. It requires attention to technique and the appropriate choice of therapy for a given patient at a given point in time. Subjects must be monitored continuously after initiation of therapy for control of bleeding, and second-line definitive therapies must be introduced quickly if endoscopic and pharmacologic treatment fails. PMID- 26142037 TI - Hemostatic Powders in Gastrointestinal Bleeding: A Systematic Review. AB - Topical hemostatic agents and powders are an emerging modality in the endoscopic management of upper and lower gastrointestinal bleeding. This systematic review demonstrates the effectiveness and safety of these agents with special emphasis on TC-325 and Ankaferd Blood Stopper. The unique noncontact/nontraumatic application, ability to cover large areas of bleed, and ease of use make these hemostatic agents an attractive option in certain clinical situations, such as massive bleeding with poor visualization, salvage therapy, and diffuse bleeding from luminal malignancies. PMID- 26142038 TI - New Technologies and Approaches to Endoscopic Control of Gastrointestinal Bleeding. AB - Endoscopic treatment of gastrointestinal (GI) bleeding is considered the first line of therapy. Although standard techniques, such as epinephrine injection, through-the-scope hemoclips, bipolar coagulation, argon plasma coagulation, and band ligation are routinely used, some GI bleeds are refractory to these therapies. Newer technologies have emerged to assist with the treatment of GI bleeding. This article highlights endoscopic and endoscopic ultrasound-guided therapies that may be used by experienced endoscopists for the primary control of GI bleeding or for cases refractory to standard hemostatic techniques. PMID- 26142039 TI - Management of Patients with Rebleeding. AB - Peptic ulcer bleeding is a common emergency. Management of ulcer bleeding requires prompt risk stratification, initiation of pharmacotherapy, and timely evaluation for endoscopy. Although endoscopy can achieve primary hemostasis in more than 90% of peptic ulcer bleeding, rebleeding may occur in up to 15% of patients after therapeutic endoscopy and is associated with heightened mortality. Early identification of high-risk patients for rebleeding is important. Depending on bleeding severity and center availability, patients with rebleeding may be managed by second endoscopy, transarterial angiographic embolization, or surgery. This article reviews the current management of peptic ulcers with an emphasis on rebleeding. PMID- 26142040 TI - Unusual Causes of Upper Gastrointestinal Bleeding. AB - Upper gastrointestinal (GI) bleeding is an important clinical condition managed routinely by endoscopists. Diagnostic and therapeutic options vary immensely based on the source of bleeding and it is important for the gastroenterologist to be cognizant of both common and uncommon etiologies. The focus of this article is to highlight and discuss unusual sources of upper GI bleeding, with a particular emphasis on both the clinical and endoscopic features to help diagnose and treat these atypical causes of bleeding. PMID- 26142041 TI - Tips and Tricks on How to Optimally Manage Patients with Upper Gastrointestinal Bleeding. AB - Effective endoscopic therapy for upper gastrointestinal (GI) bleeding has been shown to reduce rebleeding, need for surgery, and mortality. Effective endoscopic management of acute upper GI bleeding can be challenging and worrying. This article provides advice that is complementary to the in-depth reviews that accompany it in this issue. Topics include initial management, resuscitation, when and where to scope, benefits and limitations of devices, device selection based on lesion characteristics, improving visualization to localize the lesion, and tips on how to reduce the endoscopist's trepidation about managing these cases. PMID- 26142043 TI - Advances and Improvements in the Management of Upper Gastrointestinal Bleeding. PMID- 26142044 TI - Nationwide prevalence of human papillomavirus infection and viral genotype distribution in 37 cities in China. AB - BACKGROUND: Type-specific high-risk HPV (hrHPV) infection is related to cervical carcinogenesis. The prevalence of hrHPV infection varies geographically, which might reflect the epidemiological characteristics of cervical cancer among different populations. To establish a foundation for HPV-based screening and vaccination programs in China, we investigated the most recent HPV prevalence and genotypic distributions in different female age groups and geographical regions in China. METHODS: In 2012, a total of 120,772 liquid-based cytological samples from women enrolled for population- or employee-based cervical screening in 37 Chinese cities were obtained by the Laboratory of Molecular Infectious Diseases of Guangzhou KingMed. A total of 111,131 samples were tested by Hybrid Capture II and the other 9,641 were genotyped using the TellgenplexTM HPV DNA Assay. RESULTS: The total positive rate for hrHPV was 21.07 %, which ranged from 18.42 % (Nanchang) to 31.94 % (Haikou) and varied by region. The regions of Nanchang, Changsha, Hangzhou, Chengdu, Fuzhou, Guangdong, and Guiyang could be considered the low prevalence regions. Age-specific prevalence showed a "two-peak" pattern, with the youngest age group (15-19 years) presenting the highest hrHPV infection rate (30.55 %), followed by a second peak for the 50-60-year-old group. Overall, the most prevalent genotypes were HPV16 (4.82 %) and HPV52 (4.52 %), followed by HPV58 (2.74 %). Two genotypes HPV6 (4.01 %) and HPV11 (2.29 %) were predominant in the low-risk HPV (lrHPV) type, while the mixed genotypes HPV16 + 52 and HPV52 + 58 were most common in women with multiple infections. CONCLUSIONS: This study shows that HPV infection in China has increased to the level of an "HPV-heavy burden" zone in certain regions, with prevalence varying significantly among different ages and regions. Data from this study represent the most current survey of the nationwide prevalence of HPV infection in China, and can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs. PMID- 26142045 TI - The major facilitator superfamily transporter Knq1p modulates boron homeostasis in Kluyveromyces lactis. AB - Boron is an essential micronutrient for living cells, yet its excess causes toxicity. To date, the mechanisms of boron toxicity are poorly understood. Recently, the ScATR1 gene has been identified encoding the main boron efflux pump in Saccharomyces cerevisiae. In this study, we analyzed the ScATR1 ortholog in Kluyveromyces lactis--the KNQ1 gene, to understand whether it participates in boron stress tolerance. We found that the KNQ1 gene, encoding a permease belonging to the major facilitator superfamily, is required for K. lactis boron tolerance. Deletion of the KNQ1 gene led to boron sensitivity and its overexpression increased K. lactis boron tolerance. The KNQ1 expression was induced by boron and the intracellular boron concentration was controlled by Knq1p. The KNQ1 promoter contains two putative binding motifs for the AP-1-like transcription factor KlYap1p playing a central role in oxidative stress defense. Our results indicate that the induction of the KNQ1 expression requires the presence of KlYap1p and that Knq1p like its ortholog ScAtr1p in S. cerevisiae functions as a boron efflux pump providing boron resistance in K. lactis. PMID- 26142046 TI - A coupled non-Fickian model of a cardiovascular drug delivery system. AB - A coupled non-Fickian model of a cardiovascular drug delivery system using a biodegradable drug-eluting stent is proposed. The numerical results are obtained using an implicit-explicit finite-element method. The influence of vessel stiffness on the transport of drug eluted from the stent is analysed. The results presented in this paper suggest new perspectives to adapt the drug delivery profile to the needs of the patient. PMID- 26142047 TI - At last, vaccine-induced protection against Helicobacter pylori. PMID- 26142049 TI - Intraoperative monitoring during decompression of the spinal cord and spinal nerves using transcranial motor-evoked potentials: The law of twenty percent. AB - Motor-evoked potential (MEP) monitoring was performed during 196 consecutive spinal (79 cervical and 117 lumbar) surgeries for the decompression of compressive spinal and spinal nerve diseases. MEP monitoring in spinal surgery has been considered sensitive to predict postoperative neurological recovery. In this series, transcranial stimulation consisted of trains of five pulses at a constant voltage (200-600 V). For the normalization of MEP, we recorded compound muscle action potentials (CMAP) after peripheral nerve stimulation, usually on the median nerve at the wrist 2 seconds before or after each transcranial stimulation of the motor area, for all operations. The sensitivity and specificity of MEP monitoring was 100% and 97.4%, respectively, or 96.9% with or without CMAP compensation (if the threshold of postoperative motor palsy was defined as 20% relative amplitude rate [RAR]). The mean RAR after CMAP normalization, of the most affected muscle in the patient group with excellent postoperative results (recovery rate of a Japan Orthopedic Association score of more than 50%) was significantly higher than that in the other groups (p=0.0224). All patients with an amplitude increase rate (AIR) with CMAP normalization of more than 20% achieved neurological recovery postoperatively. Our results suggest that if the RAR is more than 20%, postoperative motor palsy can be avoided in spinal surgery. If the AIR with normalization by CMAP after peripheral nerve stimulation is more than 20%, neurological recovery can be expected in spinal surgery. PMID- 26142048 TI - Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial. AB - BACKGROUND: Helicobacter pylori is one of the most common gastric pathogens, affecting at least half the world's population, and is strongly associated with gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma. We aimed to assess the efficacy, safety, and immunogenicity of a three-dose oral recombinant H pylori vaccine in children in China. METHODS: We did this randomised, double blind, placebo-controlled, phase 3 trial at one centre in Ganyu County, Jiangsu Province, China. Healthy children aged 6-15 years without past or present H pylori infection were randomly assigned (1:1), via computer-generated randomisation codes in blocks of ten, to receive the H pylori vaccine or placebo. Participants, their guardians, and study investigators were masked to treatment allocation. The primary efficacy endpoint was the occurrence of H pylori infection within 1 year after vaccination. We did analysis in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT02302170. FINDINGS: Between Dec 2, 2004, and March 19, 2005, we randomly assigned 4464 participants to either the vaccine group (n=2232) or the placebo group (n=2232), of whom 4403 (99%) participants completed the three-dose vaccination schedule and were included in the per-protocol efficacy analysis. We extended follow-up to 3 years. We recorded 64 events of H pylori infection within the first year (14 events in 2074.3 person-years at risk in the vaccine group vs 50 events in 2089.6 person-years at risk in the placebo group), resulting in a vaccine efficacy of 71.8% (95% CI 48.2-85.6). 157 (7%) participants in the vaccine group and 161 (7%) participants in the placebo group reported at least one adverse reaction. Serious adverse events were reported in five (<1%) participants in the vaccine group and seven (<1%) participants in the placebo group, but none was considered to be vaccination related. INTERPRETATION: The oral recombinant H pylori vaccine was effective, safe, and immunogenic in H pylori-naive children. This vaccine could substantially reduce the incidence of H pylori infection; however, follow up over a longer period is needed to confirm the protection of the vaccine against H pylori-associated diseases. FUNDING: Chongqing Kangwei Biological Technology. PMID- 26142050 TI - A minimally invasive anterior skull base approach for evacuation of a basal ganglia hemorrhage. AB - We describe the technical nuances of a minimally invasive anterior skull base approach for microsurgical evacuation of a large basal ganglia hematoma through an endoport. Patients who suffer from large spontaneous intracerebral hemorrhages (ICH) of the basal ganglia have a very poor prognosis. However, the benefit of surgery for the management of ICH is controversial. The development of endoport technology has allowed for minimally invasive access to subcortical lesions, and may offer unique advantages over conventional surgical techniques due to less disruption of the overlying cortex and white matter fiber tracts. A 77-year-old man presented with a hypertensive ICH of the right putamen, measuring 9 cm in maximal diameter and 168 cm(3) in volume. We planned an endoport trajectory through the long axis of the hematoma using frameless stereotactic neuronavigation. In order to access the optimal cortical entry point at the lateral aspect of the basal frontal lobe, a miniature modified orbitozygomatic skull base craniotomy was performed through an incision along the superior border of the right eyebrow. Using the BrainPath endoport system (NICO, Indianapolis, IN, USA), the putaminal hematoma was successfully evacuated, resulting in an 87% postoperative reduction in ICH volume. Thus, we show that, in appropriately selected cases, endoport-assisted microsurgery is safe and effective for the evacuation of large ICH. Furthermore, minimally invasive anterior skull base approaches can be employed to expand the therapeutic potential of endoport assisted approaches to include subcortical lesions, such as hematomas of the basal ganglia. PMID- 26142051 TI - Poor prognosis despite aggressive treatment in adults with intramedullary spinal cord glioblastoma. AB - We report our institution's experience with adult patients who underwent surgery for intramedullary spinal cord glioblastoma. Spine involvement of glioblastoma is rare, representing 7.5% of all intramedullary gliomas and 1-3% of all spinal cord tumors. We performed a retrospective review of five male patients with intramedullary spinal cord glioblastoma who underwent surgical resection from 1990 to 2014. Demographic, operative, and postoperative factors were recorded. The median age at treatment was 31 years (range: 18-61) and all men presented with motor or sensory dysfunction. Two had prior surgical resection of an intramedullary World Health Organization Grade III anaplastic astrocytoma lesion with adjuvant chemoradiation. All tumors were present in the cervical (n=2; 40%) or thoracic (n=3; 60%) spine, spanning a median of three levels (range: 2-4). Gross total resection was achieved in three men (60%), and there were no intraoperative mortalities or complications. Although one had improvement in his neurological status postoperatively, all five men died with a median time to death of 20 months (range: 2-31). Adult intramedullary spinal cord glioblastoma is rare, and despite aggressive treatment, prognosis is poor, with a median survival in our series of only 20 months. New treatment strategies are necessary to improve survival in this patient population. PMID- 26142052 TI - Influence of Combined Hill-Sachs and Bony Bankart Defects on Range of Motion in Anterior Instability of the Shoulder in a Finite Element Model. AB - PURPOSE: To quantify the effect of different size combinations of Hill-Sachs defects and bony Bankart defects on shoulder instability across a broad range of motion. METHODS: A computer-based finite element approach was used to model an intact glenohumeral joint. Defects were created for the glenoid with respect to its width (12.5%, 25%, 37.5%, and 50%). The defect sizes chosen for the humeral head were 6%, 19%, 31%, and 44% of the diameter. Simulations were analyzed using quasi-static analysis with displacement control under 50 N of medial compression. Distance to dislocation (DTD) was the primary outcome. RESULTS: Every progressive bony Bankart defect lowered the value of DTD (P < .0001). These DTD values of individual glenoid defects were the same for every abduction and rotation angle. This may be an artifact due to the glenoid's spherical-shape assumption, which was necessary for the sample-specific model and is not a completely accurate representation of specimen-specific geometry. The largest glenoid defect size had a DTD value of 0 mm, which signifies no contact between surfaces. At 90 degrees of abduction, Hill-Sachs defect sizes 19%, 31% (P < .0001), and 44% (P < .0001) further reduced DTD values gradually after 30 degrees of external rotation, 10 degrees of external rotation, and 20 degrees of internal rotation, respectively. This signifies loss of contact between articulating surfaces, resulting in reduced motion. However, at a 45 degrees abduction angle, the loss of contact only occurred for humeral head defect sizes 31% and 44%. CONCLUSIONS: This model shows that increasing shoulder instability is predicted by increasing humeral head and glenoid defect sizes for a broad envelope of motion. The size of glenoid defect can be used to determine the baseline stability. An additional humeral head defect can further reduce the stability when the arm is in external rotation because of loss of contact. CLINICAL RELEVANCE: The data from this study will be helpful in establishing thresholds for performing bony reconstructions. PMID- 26142053 TI - Two-item same/different discrimination in rhesus monkeys (Macaca mulatta). AB - Almost all nonhuman animals can recognize when one item is the same as another item. It is less clear whether nonhuman animals possess abstract concepts of "same" and "different" that can be divorced from perceptual similarity. Pigeons and monkeys show inconsistent performance, and often surprising difficulty, in laboratory tests of same/different learning that involve only two items. Previous results from tests using multi-item arrays suggest that nonhumans compute sameness along a continuous scale of perceptual variability, which would explain the difficulty of making two-item same/different judgments. Here, we provide evidence that rhesus monkeys can learn a two-item same/different discrimination similar to those on which monkeys and pigeons have previously failed. Monkeys' performance transferred to novel stimuli and was not affected by perceptual variations in stimulus size, rotation, view, or luminance. Success without the use of multi-item arrays, and the lack of effect of perceptual variability, suggests a computation of sameness that is more categorical, and perhaps more abstract, than previously thought. PMID- 26142054 TI - Understanding vitamin D deficiency in intensive care patients. PMID- 26142055 TI - Central venous catheter malposition into pulmonary vein: an unusual cause of epileptic seizures. PMID- 26142057 TI - Psychiatric symptoms during oseltamivir treatment. PMID- 26142056 TI - Retinal prostheses in degenerative retinal diseases. AB - Degenerative retinal diseases may lead to significant loss of vision. Age-related macular degeneration (AMD) and retinitis pigmentosa (RP), which eventually affect the photoreceptors, are the two most common retinal degenerative diseases. Once the photoreceptorcells are lost, there are no known effective therapies for AMD or RP. The concept of retinal prosthesis is to elicit neural activity in the remaining retinal neurons by detecting light and converting it into electrical stimuli using artificial devices. Subretinal, epiretinal, and other retinal prostheses implants are currently designed to restore functional vision in retinal degenerative diseases. In this review, we have summarized different types of retinal prostheses, implant locations, and visual outcomes. Our discussions will further elucidate the results from clinical trials, and the challenges that will need to be overcome to more efficaciously assist patients with AMD and RP in the future. PMID- 26142058 TI - Integrative taxonomy detects cryptic and overlooked fish species in a neotropical river basin. AB - The great freshwater fish diversity found in the neotropical region makes management and conservation actions challenging. Due to shortage of taxonomists and insufficient infrastructure to deal with such great biodiversity (i.e. taxonomic impediment), proposed remedies to accelerate species identification and descriptions include techniques that combine DNA-based identification and concise morphological description. The building of a DNA barcode reference database correlating meristic and genetic data was developed for 75 % of the Mucuri River basin's freshwater fish. We obtained a total of 141 DNA barcode sequences from 37 species belonging to 30 genera, 19 families, and 5 orders. Genetic distances within species, genera, and families were 0.74, 9.5, and 18.86 %, respectively. All species could be clearly identified by the DNA barcodes. Divergences between meristic morphological characteristics and DNA barcodes revealed two cryptic species among the Cyphocharax gilbert and Astyanax gr. bimaculatus specimens, and helped to identify two overlooked species within the Gymnotus and Astyanax taxa. Therefore, using a simplified model of neotropical biodiversity, we tested the efficiency of an integrative taxonomy approach for species discovery, identification of cryptic diversity, and accelerating biodiversity descriptions. PMID- 26142059 TI - In Vivo Confocal Microscopy after Corneal Collagen Crosslinking. AB - In vivo confocal microscopy (IVCM) findings of 84 patients who had undergone conventional epithelium-off corneal collagen crosslinking (CXL) and accelerated CXL (ACXL) were retrospectively reviewed. Analysis confirmed that despite a significant decrease in the mean density of anterior keratocytes in the first 6 postoperative months, cell density after CXL and ACXL returned to baseline values at 12 months. The demarcation lines observed after treatments represent an expression of light-scattering (reflectivity changes) through different tissue densities. Temporary haze of the anterior-mid stroma after conventional CXL represents an indirect sign of CXL-induced stromal collagen compaction and remodeling. IVCM showed that treatment penetration varies to some extent, but that the endothelium is not damaged and is correlated with CXL biomechanical effects. IVCM of limbal structures shows no evidence of pathological changes. Regeneration of subepithelial and stromal nerves was complete 12 months after the operation with fully restored corneal sensitivity and no neurodystrophic occurrences. IVCM allowed detailed high magnification in vivo micromorphological analysis of corneal layers, enabling the assessment of early and late corneal modifications induced by conventional and accelerated CXL. IVCM confirms that CXL is a safe procedure, which is still undergoing development and protocol adjustments. PMID- 26142060 TI - Risk of Nursing Home Admission After Femoral Fracture Compared With Stroke, Myocardial Infarction, and Pneumonia. AB - OBJECTIVE: To analyze the burden of institutionalizations after femoral fracture and compare it with other "catastrophic" disease entities like stroke, myocardial infarction, or pneumonia. DESIGN/SETTING/PARTICIPANTS: Routine data of 414,000 hospitalized German patients aged 66 years and older were used to calculate institutionalization risks after femoral fracture, stroke, myocardial infarction, pneumonia or a combined group of "all other hospitalizations." MEASUREMENTS: Institutionalization was defined as nursing home admission within 6 months after discharge from hospital. Age- and sex-specific incidence and incidence rates of institutionalization were calculated. To compare the risk of institutionalization between the disease entities, age-standardized rates were computed and proportional hazards models were applied. In-house mortality and mortality after discharge from hospital were also calculated. RESULTS: The risk of institutionalization increased exponentially with age in all disease entities. For example, the risk of institutionalization after femoral fracture increased from 3.6% in women aged 65 to 69 years to 34.8% in women aged 95 years and older. The highest institutionalization rates were observed in patients with stroke, followed by femoral fracture, pneumonia, and myocardial infarction. In men, the age-standardized risk of institutionalization was almost as high after femoral fracture as after stroke (7.5% vs 8.0%). In contrast to myocardial infarction and pneumonia, femoral fracture and stroke were more likely to be followed by institutionalization rather than death. CONCLUSION: Femoral fractures result in high burden of institutionalizations. Prevention of falls, diagnosis and treatment of osteoporosis, and high-quality rehabilitation are challenges to tackle the burden of institutionalization in these patients in the future. PMID- 26142061 TI - Complete genome sequence of the glidobactin producing strain [Polyangium] brachysporum DSM 7029. AB - [Polyangium] brachysporum DSM7029 can produce glidobactin, which is a peptide based proteasome inhibitor that shows great potential as an anticancer drug. To better understand the glidobactin biosynthesis mechanism and to aid further studies of this strain, we report the annotated complete genome sequence of DSM7029, which is 6,476,147 bp in length. PMID- 26142062 TI - Complete genome sequence of Bifidobacterium angulatum JCM 7096(T) isolated from human feces. AB - Bifidobacterium angulatum JCM 7096(T) was isolated from human feces. Here we report the complete genome sequence of this organism. This paper is the first report demonstrating the fully sequenced and completely annotated genome of a B. angulatum strain. PMID- 26142063 TI - Complete genome sequence of Bifidobacterium breve JCM 1192(T) isolated from infant feces. AB - Bifidobacterium breve JCM 1192(T) was isolated from infant feces. Here, we report the complete genome sequence of this organism. PMID- 26142064 TI - Electroinduced release of recombinant beta-galactosidase from Saccharomyces cerevisiae. AB - Yeasts are one of the most commonly used systems for recombinant protein production. When the protein is intracelullarly expressed the first step comprises a cell lysis, achieved usually by a mechanical disintegration. This leads to non-selective liberation of the cytoplasmic content, which complicates the following downstream process. Here, we present a new approach suitable for more selective and efficient recovery of large intracellular proteins from yeast, based on the combination of electropermeabilisation and subsequent treatment with lytic enzyme. The experiments were performed with Saccharomyces cerevisiae strains expressing LYTAG-beta-galactosidase from Escherichia coli. The permeabilzation of plasma membrane was induced by application of rectangular electric pulses, with 1.25ms duration and field intensity of 4.3-5.4kV/cm. In the presence of a reducing agent the cells released approximately 80% of the total protein 4h after electrical treatment. At the same conditions the release of the recombinant protein was very slow, reaching 45% from total activity 20h after pulse application. The great difference in the release kinetics enabled to remove a part of the total protein, without significant loss of beta-galactosidase activity, only by substituting the incubation buffer. The subsequent addition of lyticase (1-2U/ml) led to recovery of approximately 70% from the recombinant enzyme, with a factor of purification 2.6, without provoking a significant cell lysis. The applicability of similar protocol for liberation of large recombinant and native proteins from yeast is discussed. PMID- 26142065 TI - Impact of Immunoglobulin Therapy in Pediatric Disease: a Review of Immune Mechanisms. AB - Intravenous immunoglobulin (IVIG) provides replacement therapy in immunodeficiency and immunomodulatory therapy in inflammatory and autoimmune diseases. This paper describes the immune mechanisms underlying six major non primary immunodeficiency pediatric diseases and the diverse immunomodulatory functions of IVIG therapy. In Kawasaki disease, IVIG plays a major, proven, and effective role in decreasing aneurysm formation, which represents an aberrant inflammatory response to an infectious trigger in a genetically predisposed individual. In immune thrombocytopenia, IVIG targets the underlying increased platelet destruction and decreased platelet production. Although theoretically promising, IVIG shows no clear clinical benefit in the prophylaxis and treatment of neonatal sepsis. Limitations in research design combined with the unique neonatal immunologic environment offer explanations for this finding. Inflammation from aberrant immune activation underlies the myelinotoxic effects of Guillain-Barre syndrome. HIV-1 exerts a broad range of immunologic effects and was found to decrease serious bacterial infections in the pre-highly active anti retroviral therapy (HAART) era, although its practical relevance in the post HAART era has waned. Clinical and experimental data support the role of immune mechanisms in the pathogenesis of childhood epilepsy. IVIG exerts anti-epileptic effects through targeting upregulated cytokine pathways and antibodies thought to contribute to epilepsy. Applications in six additional pediatric diseases including pediatric asthma, atopic dermatitis, cystic fibrosis, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), autism, and transplantation will also be briefly reviewed. From autoimmunity to immunodeficiency, a dynamic immunologic basis underlies major pediatric diseases and highlights the broad potential of IVIG therapy. PMID- 26142068 TI - Resident Self-Assessment and Learning Goal Development: Evaluation of Resident Reported Competence and Future Goals. AB - OBJECTIVE: To determine incidence of learning goals by competency area and to assess which goals fall into competency areas with lower self-assessment scores. METHODS: Cross-sectional analysis of existing deidentified American Academy of Pediatrics' PediaLink individualized learning plan data for the academic year 2009-2010. Residents self-assessed competencies in the 6 Accreditation Council for Graduate Medical Education (ACGME) competency areas and wrote learning goals. Textual responses for goals were mapped to 6 ACGME competency areas, future practice, or personal attributes. Adjusted mean differences and associations were estimated using multiple linear and logistic regression. RESULTS: A total of 2254 residents reported 6078 goals. Residents self-assessed their systems-based practice (51.8) and medical knowledge (53.0) competencies lowest and professionalism (68.9) and interpersonal and communication skills (62.2) highest. Residents were most likely to identify goals involving medical knowledge (70.5%) and patient care (50.5%) and least likely to write goals on systems-based practice (11.0%) and professionalism (6.9%). In logistic regression analysis adjusting for postgraduate year (PGY), gender, and degree type (MD/DO), resident reported goal area showed no association with the learner's relative self assessment score for that competency area. In the conditional logistic regression analysis, with each learner serving as his or her own control, senior residents (PGY2/3+s) who rated themselves relatively lower in a competency area were more likely to write a learning goal in that area than were PGY1s. CONCLUSIONS: Senior residents appear to develop better skills and/or motivation to explicitly turn self-assessed learning gaps into learning goals, suggesting that individualized learning plans may help improve self-regulated learning during residency. PMID- 26142067 TI - Treatment Interventions for Early Childhood Obesity: A Systematic Review. AB - CONTEXT: With 25% of preschool-age children in the United States being overweight or obese, effective interventions for these children would have significant public health implications. Randomized trials targeting this age group have been performed since the last systematic review. OBJECTIVE: To systematically review the literature on treatment interventions for overweight or obesity in preschool age children. DATA SOURCES: Medline (1948-July 2014), the Cochrane Central Registry (1991-July 2014), CINAHL (1990-July2014), and PAS abstracts (2000-2014). STUDY SELECTION: Inclusion criteria were children aged 0 to 6 in the study and adiposity as an outcome. Exclusions were having normal-weight children in the trial and not having a comparison group. DATA EXTRACTION: Data were extracted independently by 2 authors using a template. RESULTS: The initial search yielded 1981 results, narrowed to 289 abstracts after initial review. Further analysis and cross-referencing led to the selection of 6 randomized controlled trials representing 1222 children. Two studies used systems changes and motivational interviewing and showed no significant effect on adiposity. Two studies used an intensive, multidisciplinary approach over 6 months and demonstrated significant decreases in adiposity. One study tested parental coaching and showed a significant reduction in adiposity at 6 months. One study used education on a dairy-rich diet and showed a possible effect on adiposity. LIMITATIONS: The study designs were too heterogeneous for meta-analysis; few ethnic minority subjects were included. CONCLUSIONS: Multidisciplinary, intensive interventions have some evidence of efficacy in reducing adiposity in preschool children. PMID- 26142066 TI - Endothelial Dysfunction and Nailfold Videocapillaroscopy Pattern as Predictors of Digital Ulcers in Systemic Sclerosis: a Cohort Study and Review of the Literature. AB - Raynaud's phenomenon and digital ulcers (DUs) are frequent among systemic sclerosis (SSc) patients. Our aim was to investigate the diagnostic and predictive value for DU of endothelial dysfunction biomarkers (flow-mediated dilatation (FMD), serum levels of endothelin-1 (ET-1), and ADMA), angiogenic/angiostatic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin), and nailfold videocapillaroscopy (NVC). We compared our results with a literature review. In a cohort study of 77 SSc patients, we followed two groups of patients: (i) naive DU patients (39) and (ii) active DU at baseline (38 patients) for 3 years. Telangiectasia (p < 0.001) and diffuse disease subset (p = 0.001) were significantly more frequent in patients with active DU at enrolment. Additionally, NVC late scleroderma pattern (AUC 0.846, 95%CI 0.760-0.932), lower values of FMD (AUC 0.754, 95%CI 0.643-0.864), increased serum levels of ET-1 (AUC 0.758, 95%CI 0.649-0.866), ADMA (AUC 0.634, 95%CI 0.511 0.757), and endoglin as well as low VEGF serum levels (AUC 0.705, 95%CI 0.579 0.830) were significantly associated to new DU events in the 3-year follow-up. Cox regression analysis showed that FMD > 9.41 % (HR 0.37, 95%CI 0.14-0.99); ET-1 >11.85 pmol/L (HR 3.81, 95%CI 1.41-10.26) and late NVC pattern (HR 2.29, 95%CI 0.97-5.38) were independent predictors of DU recurrence. When estimating the probability of occurrence of first DU in naive DU patients, only late NVC pattern (HR 12.66, 95%CI 2.06-77.89) was an independent predictor factor. In conclusion, late scleroderma patterns in NVC are the best independent predictors of SSc patients who are at risk of developing DU. Endothelial dysfunction assessed by FMD and ET-1 was also found to be an independent predictor of DU recurrence in a 3-year follow-up. PMID- 26142069 TI - Understanding Barriers to Early Intervention Services for Preterm Infants: Lessons From Two States. AB - OBJECTIVE: To explore existing barriers and challenges to Early Intervention (EI) referral, enrollment, and service provision for very low birth weight (VLBW; <1500 g) infants. METHODS: We conducted 10 focus groups with parents of VLBW children (n = 44) and 32 interviews with key informants from EI (n = 7), neonatal intensive care units (n = 17), and outpatient clinics (n = 8) at 6 sites in 2 states. We used grounded theory to identify themes about gaps in services. RESULTS: Both parents and providers found EI helpful. However, they also identified gaps in the current EI system at the levels of eligibility, referral, family receptivity, and service provision and coordination with medical care. Inadequate funding and variable procedures for evaluation may affect children's eligibility. Referrals can be missed as a result of simple oversight or communication failure among hospitals, EI, and families; referral outcomes often are not formally tracked. Families may not be receptive to services as a result of wariness of home visits, social stressors, denial about potential developmental delays, or lack of understanding of the benefits of EI. Once a child is deemed eligible, services may be delayed or terminated early, and EI providers may have little specialized training. Communication and coordination with the child's medical care team is often limited. CONCLUSIONS: Systemic barriers, including funding and staffing issues, state and federal regulations, and communication with families and medical providers, have led to gaps in the EI system. The chronic care model may serve as a framework for integrating community based interventions like EI with medical care for VLBW children and other vulnerable populations. PMID- 26142070 TI - Examining Trends and Coexisting Conditions Among Children Qualifying for SSI Under ADHD, ASD, and ID. AB - OBJECTIVE: To examine the prevalence trends and coexisting conditions in attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID) in the pediatric Supplemental Security Income (SSI) population and general population. METHODS: The Social Security Administration (SSA) provided data on primary and secondary diagnoses of children qualifying for SSI for years 2000 to 2011. We compared SSA data with 2000-2011 National Health Interview Survey data on the prevalence of mental health diagnoses among children in the general population living between 0 and 199% of the federal poverty line. We utilized linear regression analysis to test the statistical significance of differences in the trends of the conditions' prevalence. RESULTS: Over this time period, the SSI population experienced increases in ADHD (5.8%) and ASD (7.2%) and a decrease in ID (-10.3%). Comparison with change in the general population indicated no significant difference in ADHD but significant differences in ASD and ID. Relative percentage changes reflect similar changes. The SSI population qualifying for SSI with ADHD (70.8%) had higher rates of coexisting conditions than the general population (66.1%), but lower rates of coexisting conditions for ASD and ID. CONCLUSIONS: ADHD is on the rise among children receiving SSI and in the general population. This suggests that the rise of ADHD in the SSI population is expected and does not represent a misallocation of resources. Changes described among the SSI population in ASD and ID may allude to diagnostic/coding trends and/or true changes in prevalence. Limitations arise from the comparability of the 2 data sets. PMID- 26142071 TI - The Accuracy of ICD Codes: Identifying Physical Abuse in 4 Children's Hospitals. AB - OBJECTIVE: To assess the accuracy of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), codes in identifying cases of child physical abuse in 4 children's hospitals. METHODS: We included all children evaluated by a child abuse pediatrician (CAP) for suspicion of abuse at 4 children's hospitals from January 1, 2007, to December 31, 2010. Subjects included both patients judged to have injuries from abuse and those judged to have injuries from accidents or to have medical problems. The ICD-9-CM codes entered in the hospital discharge database for each child were compared to the decisions made by the CAPs on the likelihood of abuse. Sensitivity and specificity were calculated. Medical records for discordant cases were abstracted and reviewed to assess factors contributing to coding discrepancies. RESULTS: Of 936 cases of suspected physical abuse, 65.8% occurred in children <1 year of age. CAPs rated 32.7% as abuse, 18.2% as unknown cause, and 49.1% as accident/medical cause. Sensitivity and specificity of ICD-9-CM codes for abuse were 73.5% (95% confidence interval 68.2, 78.4), and 92.4% (95% confidence interval 90.0, 94.0), respectively. Among hospitals, sensitivity ranged from 53.8% to 83.8% and specificity from 85.4% to 100%. Analysis of discordant cases revealed variations in coding practices and physicians' notations among hospitals that contributed to differences in sensitivity and specificity of ICD-9-CM codes in child physical abuse. CONCLUSIONS: Overall, the sensitivity and specificity of ICD-9-CM codes in identifying cases of child physical abuse were relatively low, suggesting both an under- and overcounting of abuse cases. PMID- 26142073 TI - Significantly prolonged spinal anesthesia with the addition of dexamethasone: a case report. AB - The purpose of the study is to highlight that prolonged blocks with spinal anesthesia are not usually due to neurologic defects. Consent for data publication was obtained. A 35-year-old female patient with right upper tibial chondrosarcoma was planned to undergo excision and reconstruction with a free vascularized fibular graft. The patient had no significant medical history. We gave spinal anesthesia, which is to be continued with general anesthesia after regression of the sensory level. After 3 hours, we evaluated the patient for the second time to find sensory block at T10 level. It was decided to carry out these evaluations hourly and wait for general anesthesia. Ten hours after the spinal anesthesia, the sensory block was still at T10 level. After 13 hours, the surgical procedure was finished, and the sensory block was still at T10 level and the motor block according to the Bromage scale remained at grade 4. A computed tomography was performed and did not reveal signs of spinal compression, spinal canal stenosis, or other anomalies (magnetic resonance imaging was unavailable). A complete motor and sensory recovery from the spinal block was observed 20 hours after spinal anesthesia. We present a case of major microscopic surgery done over 13 hours with a single shot of spinal anesthesia in a 35-year-old female patient. Complete recovery of sensory and motor blocks has been after 20 hours. We also review other cases of unusually prolonged spinal blocks and the possible differential diagnosis for that. PMID- 26142072 TI - Feedback associated with expectation for larger-reward improves visuospatial working memory performances in children with ADHD. AB - We tested the interactive effect of feedback and reward on visuospatial working memory in children with ADHD. Seventeen boys with ADHD and 17 Normal Control (NC) boys underwent functional magnetic resonance imaging (fMRI) while performing four visuospatial 2-back tasks that required monitoring the spatial location of letters presented on a display. Tasks varied in reward size (large; small) and feedback availability (no-feedback; feedback). While the performance of NC boys was high in all conditions, boys with ADHD exhibited higher performance (similar to those of NC boys) only when they received feedback associated with large reward. Performance pattern in both groups was mirrored by neural activity in an executive function neural network comprised of few distinct frontal brain regions. Specifically, neural activity in the left and right middle frontal gyri of boys with ADHD became normal-like only when feedback was available, mainly when feedback was associated with large-reward. When feedback was associated with small-reward, or when large-reward was expected but feedback was not available, boys with ADHD exhibited altered neural activity in the medial orbitofrontal cortex and anterior insula. This suggests that contextual support normalizes activity in executive brain regions in children with ADHD, which results in improved working memory. PMID- 26142074 TI - A left bevelled tube is easier inserted from the right side. PMID- 26142075 TI - Comment on "Providing information promotes greater public support for potable recycled water" by Fielding, K.S. and Roiko, A.H., 2014 [Water Research 61, 86 96]. AB - Recently, Fielding and Roiko found that information provision affects knowledge of and support for potable recycled water. However, recent cultural-sociological insights suggest that such effects are not universal. A re-analysis of the original data reveals the relevance of cultural predispositions: significant effects only exist in specific subgroups of the population. Only those who are comfortable with new technologies prove receptive to new information about potable recycled water. These findings are relevant for scholars aiming to uncover the mechanisms through which information affects public opinion, and for policymakers trying to overcome community resistance to alternative water sources. PMID- 26142076 TI - The method of averaging applied to pharmacokinetic/pharmacodynamic indirect response models. AB - The computational effort required to fit the pharmacodynamic (PD) part of a pharmacokinetic/pharmacodynamic (PK/PD) model can be considerable if the differential equations describing the model are solved numerically. This burden can be greatly reduced by applying the method of averaging (MAv) in the appropriate circumstances. The MAv gives an approximate solution, which is expected to be a good approximation when the PK profile is periodic (i.e. repeats its values in regular intervals) and the rate of change of the PD response is such that it is approximately constant over a single period of the PK profile. This paper explains the basis of the MAv by means of a simple mathematical derivation. The NONMEM(r) implementation of the MAv using the abbreviated FORTRAN function FUNCA is described and explained. The application of the MAv is illustrated by means of an example involving changes in glycated hemoglobin (HbA1c%) following administration of canagliflozin, a selective sodium glucose co transporter 2 inhibitor. The PK/PD model applied to these data is fitted with NONMEM(r) using both the MAv and the standard method using a numerical differential equation solver (NDES). Both methods give virtually identical results but the NDES method takes almost 8 h to run both the estimation and covariance steps, whilst the MAv produces the same results in less than 30 s. An outline of the NONMEM(r) control stream and the FORTRAN code for the FUNCA function is provided in the appendices. PMID- 26142077 TI - Electronic medical record integration with a database for adult congenital heart disease: Early experience and progress in automating multicenter data collection. AB - BACKGROUND: The adoption of electronic health records (EHR) has created an opportunity for multicenter data collection, yet the feasibility and reliability of this methodology is unknown. The aim of this study was to integrate EHR data into a homogeneous central repository specifically addressing the field of adult congenital heart disease (ACHD). METHODS: Target data variables were proposed and prioritized by consensus of investigators at five target ACHD programs. Database analysts determined which variables were available within their institutions' EHR and stratified their accessibility, and results were compared between centers. Data for patients seen in a single calendar year were extracted to a uniform database and subsequently consolidated. RESULTS: From 415 proposed target variables, only 28 were available in discrete formats at all centers. For variables of highest priority, 16/28 (57%) were available at all four sites, but only 11% for those of high priority. Integration was neither simple nor straightforward. Coding schemes in use for congenital heart diagnoses varied and would require additional user input for accurate mapping. There was considerable variability in procedure reporting formats and medication schemes, often with center-specific modifications. Despite the challenges, the final acquisition included limited data on 2161 patients, and allowed for population analysis of race/ethnicity, defect complexity, and body morphometrics. CONCLUSION: Large scale multicenter automated data acquisition from EHRs is feasible yet challenging. Obstacles stem from variability in data formats, coding schemes, and adoption of non-standard lists within each EHR. The success of large-scale multicenter ACHD research will require institution-specific data integration efforts. PMID- 26142078 TI - Physical and chemical effects of acoustic cavitation in selected ultrasonic cleaning applications. AB - Acoustic cavitation in a liquid medium generates several physical and chemical effects. The oscillation and collapse of cavitation bubbles, driven at low ultrasonic frequencies (e.g., 20 kHz), can generate strong shear forces, microjets, microstreaming and shockwaves. Such strong physical forces have been used in cleaning and flux improvement of ultrafiltration processes. These physical effects have also been shown to deactivate pathogens. The efficiency of deactivation of pathogens is not only dependent on ultrasonic experimental parameters, but also on the properties of the pathogens themselves. Bacteria with thick shell wall are found to be resistant to ultrasonic deactivation process. Some evidence does suggest that the chemical effects (radicals) of acoustic cavitation are also effective in deactivating pathogens. Another aspect of cleaning, namely, purification of water contaminated with organic and inorganic pollutants, has also been discussed in detail. Strong oxidising agents produced within acoustic cavitation bubbles could be used to degrade organic pollutants and convert toxic inorganic pollutants to less harmful substances. The effect of ultrasonic frequency and surface activity of solutes on the sonochemical degradation efficiency has also been discussed in this overview. PMID- 26142079 TI - Surgical Treatment of Cubital Tunnel Syndrome: Trends and the Influence of Patient and Surgeon Characteristics. AB - PURPOSE: To examine trends in and determinants of the use of different procedures for treatment of cubital tunnel syndrome. METHODS: We performed a retrospective cross-sectional analysis of the Healthcare Cost and Utilization Project Florida State Ambulatory Surgery Database for 2005 to 2012. We selected all patients who underwent in situ decompression, transposition, or other surgical treatments for cubital tunnel syndrome. We tested trends in the use of these techniques and performed a multivariable analysis to examine associations among patient characteristics, surgeon case volume, and the use of different techniques. RESULTS: Of the 26,164 patients who underwent surgery for cubital tunnel syndrome, 80% underwent in situ decompression, 16% underwent transposition, and 4% underwent other surgical treatment. Over the study period, there was a statistically significant increase in the use of in situ release and a decrease in the use of transposition. Women and patients treated by surgeons with a higher cubital tunnel surgery case volume underwent in situ release with a statistically higher incidence than other techniques. CONCLUSIONS: In Florida, surgeon practice reflected the widespread adoption of in situ release as the primary treatment for cubital tunnel syndrome, and its relative incidence increased during the study period. Patient demographics and surgeon-level factors influenced procedure selection. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 26142080 TI - Comparison of Flexor Tendon Repair Between 6-Strand Lim-Tsai With 4-Strand Cruciate and Becker Technique. AB - PURPOSE: To compare the strength of 6-strand Lim-Tsai repair with 4-strand cruciate and Becker repair, which were done using braided polyblend. We hypothesized that the biomechanical strength of 4-strand repair could be as strong as 6-strand repair because of different flexor tendon repair configurations and uneven load bearing. METHODS: We harvested 60 porcine flexor tendons. A transverse cut at the middle of the tendons was made to perform tendon repair. Six-strand Lim-Tsai repair (consisting of 2 Lim-Tsai locking loops), 4 strand cruciate repair (with 3 cross-stitch loops), and 4-strand Becker repair (with 2 double cross-stitch locking loops) were used for the repairs. The repaired tendons were pulled until failure using a mechanical tester. We recorded ultimate tensile strength, load to 2-mm gap force, stiffness, and mechanism of failure. RESULTS: The Becker repairs had significantly greater tensile strength than the cruciate and Lim-Tsai repairs. The load to 2-mm gap force and stiffness were significantly greater for cruciate repairs and Becker repairs than Lim-Tsai repairs. CONCLUSIONS: The biomechanical strength of 4-strand and Becker repairs could be as strong as 6-strand Lim-Tsai repairs. This study implies that the number of strands crossing the repair site of tendons may not be proportional to the biomechanical strength of flexor tendon repair. CLINICAL RELEVANCE: Hand surgeons are urged to be aware of the biomechanic characteristics of different flexor tendon repair techniques used in the clinical setting. PMID- 26142082 TI - Extracellular vesicles as new pharmacological targets to treat atherosclerosis. AB - Extracellular vesicles released by most cell types, include apoptotic bodies (ABs), microvesicles (MVs) and exosomes. They play a crucial role in physiology and pathology, contributing to "cell-to-cell" communication by modifying the phenotype and the function of target cells. Thus, extracellular vesicles participate in the key processes of atherosclerosis from endothelial dysfunction, vascular wall inflammation to vascular remodeling. The purpose of this review is to summarize recent findings on extracellular vesicle formation, structure, release and clearance. We focus on the deleterious and beneficial effects of extracellular vesicles in the development of atherosclerosis. The potential role of extracellular vesicles as biomarkers and pharmacological targets, their innate therapeutic capacity, or their use for novel drug delivery devices in atherosclerotic cardiovascular diseases will also be discussed. PMID- 26142081 TI - Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1-Psychometric Characteristics of 5 Paradigms. AB - Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. PMID- 26142083 TI - Propofol depresses cerebellar Purkinje cell activity via activation of GABA(A) and glycine receptors in vivo in mice. AB - Propofol is an intravenous sedative-hypnotic agen, which causes rapid and reliable loss of consciousness. Under in vitro conditions, propofol activates GABAA and glycine receptors in spinal cord, hippocampus and hypothalamus neurons. However, the effects of propofol on the cerebellar neuronal activity under in vivo conditions are currently unclear. In the present study, we examined the effects of propofol on the spontaneous activity of Purkinje cells (PCs) in urethane-anesthetized mice by cell-attached recording and pharmacological methods. Our results showed that cerebellar surface perfusion of propofol (10 1000 MUM) induced depression of the PC simple spike (SS) firing rate in a dose dependent manner, but without significantly changing the properties of complex spikes (CS). The IC50 of propofol for inhibiting SS firing of PCs was 144.5 MUM. Application of GABAA receptor antagonist, SR95531 (40 MUM) or GABAB receptor antagonist, saclofen (20 MUM), as well as glycine receptor antagonist, strychnine (10 MUM) alone failed to prevent the propofol-induced inhibition of PCs spontaneous activity. However, application the mixture of SR95531 (40 MUM) and strychnine (10 MUM) completely blocked the propofol-induced inhibition of PC SS firing. These data indicated that cerebellar surface application of propofol depressed PC SS firing rate via facilitation of GABAA and functional glycine receptors activity in adult cerebellar PCs under in vivo conditions. Our present results provide a new insight of the anesthetic action of propofol in cerebellar cortex, suggesting that propofol depresses the SS outputs of cerebellar PCs which is involved in both GABAA and glycine receptors activity. PMID- 26142084 TI - Current basis for discovery and development of aryl hydrocarbon receptor antagonists for experimental and therapeutic use in atherosclerosis. AB - The important role played by aryl hydrocarbon receptor activation in the pathophysiology of atherosclerosis induced by cigarette smoke exposure has spurred the clinical interest in the development of aryl hydrocarbon receptor antagonists with atheroprotective efficacy. A few aryl hydrocarbon receptor antagonists were developed but the lack of structural information regarding the receptor ligand binding domain resulted in several limitations in the pharmacological properties of these compounds including partial agonism, allosterism, non-selectivity, cytotoxicity and susceptibility to bioactivation. These limitations make the progress of preclinical and clinical assays with the available aryl hydrocarbon receptor antagonists difficult. There is a great interest in developing pure, competitive, selective, nontoxic and resistant to bioactivation aryl hydrocarbon receptor antagonists. Current technology permits the development of pharmacologically ideal antagonists based on the chemical features of the aryl hydrocarbon receptor ligand binding domain. According to these characteristics, chlorinated derivatives of trans-stilbene meta-substituted with electrophilic aromatic directing groups would be effective prototypes for pure, competitive, selective, nontoxic and resistant to bioactivation antagonists for such receptor. PMID- 26142085 TI - RaplixaTM: A Review in Improving Surgical Haemostasis. AB - RaplixaTM is a novel fibrin sealant containing a blend of human fibrinogen and thrombin in powder form. It is approved in adults to help control bleeding when standard surgical techniques have been insufficient. This article summarizes the product characteristics of Raplixa and provides a narrative review of its clinical use and tolerability. Unlike other available fibrin sealants, including liquid agents and lyophilized powders, the dry-powder, ready-to-use formulation of Raplixa provides potential advantages, including ease of storage and use. In the randomized, phase III FINISH-3 study, Raplixa plus gelatin sponge was superior to gelatin sponge alone in reducing the time to haemostasis in adults who developed mild or moderate bleeding uncontrolled by conventional surgical techniques while undergoing spinal, vascular, hepatic or soft-tissue surgical procedures. Raplixa was well tolerated, with a similar safety profile to that observed in the gelatin-sponge-alone group. Thus, Raplixa provides an easy to store and use option for improving haemostasis in adults when standard surgical techniques are ineffective or impractical. PMID- 26142086 TI - Hard calcified intrasellar schwannoma mimicking pituitary adenoma: a case report and review of the literature. AB - BACKGROUND: Intrasellar location of schwannoma is extremely rare, although intracranial schwannomas are common in the central nervous system. The aim of the present study is to describe a calcified intrasellar schwannoma case. MATERIALS AND METHODS: We represent a 45-year-old woman who had suffered from headaches; right side facial pain and visual disturbance which had worsen during the last week prior to admission. Physical examinations were normal except for the bitemporal visual field hemianopia which match with perimetry examination. MRI demonstrated an unusual seemingly calcified mass lesion in the sellar region which was mimicking pituitary macro adenoma. RESULT: Total resection of the tumor achieved through endoscopic transnasal transsphenoidal approach by extracapsular dissection and pathologic examination of the tumor revealed calcified schwannoma. CONCLUSION: The differential diagnoses of sellar and suprasellar lesions include pituitary adenomas, craniopharyngiomas, meningiomas, and many others. However, schwannoma is not usually included, because the occurrence of schwannoma in the sellar or suprasellar region is extremely rare. Only few cases of intrasellar schwannomas have been reported in the literature, all of which presented a suprasellar extension similar to that of our case. Fascinating surgical point is managing very firm tumor through transsphenoidal corridor which we handle it by very sharp, debulking and extracapsular removal. PMID- 26142088 TI - Editorial Introduction. PMID- 26142087 TI - Diagnostic value of serum procalcitonin for acute pyelonephritis in infants and children with urinary tract infections: an updated meta-analysis. AB - PURPOSE: The aims were to assess (1) the diagnostic value of serum procalcitonin (PCT) for acute pyelonephritis (APN) in infants and children with urinary tract infections (UTIs) and (2) to compare the performance of two commonly used cutoff values. METHODS: A meta-analysis of serum PCT in the diagnosis of APN among pediatrics with lower UTIs was conducted. The process of search strategy, publications selection and data analysis was in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: Eighteen high-quality studies with a total of 831 APN patients and 651 individuals with lower UTIs were analyzed. The overall performance of serum PCT >= 0.5 ng/mL was as follows: pooled sensitivity of 0.86 (95 % CI 0.73-0.93), pooled specificity of 0.76 (95 % CI 0.66-0.83), DOR of 18.90 (95 % CI 6.78-52.71) and AUROC of 0.86 (95 % CI 0.83-0.89), with significant heterogeneity. However, use of 1.0 ng/mL as a cutoff value produced an improved specificity of 0.91 (95 % CI 0.86-0.94), a DOR of 55.06 (95 % CI 22.57-115.48) and an AUROC of 0.94 (95 % CI 0.92-0.96), without obvious heterogeneity. CONCLUSION: In pediatrics with UTIs, the cutoff value of serum PCT, 1.0 ng/mL, has a preferable diagnostic performance compared with 0.5 ng/mL for APN. Additional prospective studies that propose an appropriate cutoff value and validate the performance of PCT for young with APN are needed in the future. PMID- 26142089 TI - Cancer Risk Counseling: How Is It Different? AB - Fifty-six of 80 (70%) full members of the National Society of Genetic Counselors with interest in cancer genetics responded to a 1994 survey regarding their cancer risk counseling practices. This study was undertaken to describe cancer risk counselors and the services they provide and to identify possible differences from general genetic counseling that warrant further study. Of 56 respondents, 41 (75%) were providing CRC. The components of CRC programs are described. Our results found significant differences between CRC and general genetic counseling in terms of training and experience of genetic counselors providing CRC and length and number of counseling sessions per consultand. 51% of respondents had 1-2 years of working in CRC, compared to 17% with 1-2 years experience in genetic counseling (p<0.05). Over one-third had 10 or more years genetic counseling experience. Counselors were more likely to see individuals at risk for cancer for longer counseling sessions (p<0.05) and for additional sessions (p<0.05). PMID- 26142090 TI - Knowledge of Breast Cancer Genetics Among Breast Cancer Patients and First-Degree Relatives of Affected Individuals. AB - The cloning of BRCA1, a susceptibility gene for inherited breast cancer, has made genetic screening possible for individuals and families whose medical histories are suggestive of an inherited predisposition to breast cancer. To date, few systematic attempts have been made to determine the level of knowledge about breast cancer genetics among women who are likely to seek BRCA1 screening when it becomes widely available. The present study attempted to assess the general knowledge about BRCA1 mutations in two groups: (1) first-degree relatives (FDRs) of breast cancer patients; and (2) women with a previous diagnosis of breast cancer. A self-administered, thirty-item questionnaire was developed through a pilot study. Ten of the items were objective, factual questions about breast cancer genetics. Responses to these questions were used to generate an overall knowledge score for each respondent. The study population was moderately knowledgeable about breast cancer genetics, with an average score of 5.35 out of 10. Counselors should not underestimate the importance of evaluating each counselee's existing knowledge about breast cancer, which can affect the provision and reception of genetic information. In particular, specific areas of knowledge that may be confusing or misunderstood were identified and these topics are discussed in detail. PMID- 26142092 TI - Complexities in Cancer Risk Counseling: Presentation of Three Cases. AB - Complexities abound in the identification and management of families at increased risk for inherited forms of cancer. One of the ways to learn as a profession how best to provide cancer risk counseling (CRC) is to share counseling experiences. Such cases can provide insight into the issues raised by families and ways in which genetic counselors have handled complex situations. Here we describe three CRC cases initially presented at the 1995 American College of Medical Genetics meeting. The first case involves balancing the importance of informing a family of the presence of an inherited cancer syndrome with the family's right "not to know." The second case illustrates the difficulties in assisting an individual to make medical management decisions in the face of uncertain risk information. The third case describes the complex interactions with a woman before and after her decision to have prophylactic surgery. PMID- 26142091 TI - The Familial Cancer Program of the Vermont Cancer Center: Development of a Cancer Genetics Program in a Rural Area. AB - In response to many scientific discoveries linking cancer in certain families to inherited factors, the Vermont Cancer Center established the Familial Cancer Program (FCP) in December 1993. This multifaceted program combines the expertise of clinicians and researchers in many disciplines, including genetics, oncology, psychology, and molecular biology. The program's goals are identification of families in its region with excess cancer, provision of clinical services to such families, and use of research protocols when available and appropriate. This article describes the experience of setting up a familial cancer program in a rural area and discusses both successes and challenges in such an endeavor. PMID- 26142094 TI - Generations Lost: A Cancer Genetics Case Report Commentary. PMID- 26142093 TI - Generations Lost: A Cancer Genetics Case Report. AB - The process of cancer genetic counseling can unearth issues that, sometimes unbeknownst to the counselor, are emotionally and psychologically significant to the patient. The following case report illustrates how the precounseling process of obtaining a medical chart on a deceased parent affected two sister counselees. This medical chart helped these sisters to reconnect with the mother they lost as children and to better understand her struggle with breast cancer. This case also chronicles the counselor's professional growth and discovery during this process. PMID- 26142095 TI - Generations Lost: A Psychological Discussion of a Cancer Genetics Case Report. PMID- 26142096 TI - Cowden Syndrome. AB - Cowden syndrome is an autosomal dominant inherited cancer syndrome characterized by multiple hamartomas which may develop in any organ. Mucocutaneous papillomas and trichilemmomas are hallmarks of the syndrome. Affected individuals are at high risk of developing both benign and malignant disease of the thyroid and breast. Epithelial thyroid carcinoma occurs in 3-10% of affected individuals while women have a 25-50% lifetime risk of developing adenocarcinoma of the breast. Because of the cancer risk, it is imperative that health care providers recognize Cowden syndrome. The susceptibility gene has been localized to 10q22-23 and preliminary studies demonstrate no genetic heterogeneity. PMID- 26142097 TI - Cancer and Peutz-Jeghers Syndrome: A Review. AB - Peutz-Jeghers syndrome is a dominantly inherited polyposis syndrome characterized by hamartomatous polyps of the gastrointestinal tract and pigmented lesions of the skin. Since its description, much debate has centered on the true malignancy risk of Peutz-Jeghers syndrome including malignancy within and outside the gastrointestinal tract. Rare tumors such as adenoma malignum of the cervix occur in Peutz-Jeghers syndrome. Likewise, more common cancers occur at younger ages in Peutz-Jeghers syndrome. Children may manifest symptoms of this disease including gastrointestinal complications and malignancy. The gene associated with this condition remains unidentified. PMID- 26142098 TI - BRCA1 Testing: Genetic Counseling Protocol Development and Counseling Issues. AB - This article discusses the genetic counseling protocols which were developed and counseling issues that have arisen in the first 2 years of evaluating a large kindred with a BRCA1 mutation. The rationale for the development of the genetic counseling protocols and specific genetic counseling visual aids are presented and discussed. The protocols and counseling aids can serve as models for other programs offering cancer susceptibility testing. The observations of study counselors about study subject concerns and responses to genetic testing at the time of the pretest and posttest counseling sessions are presented. PMID- 26142099 TI - Genetic Library. PMID- 26142100 TI - Some studies on the natural history of Graves' orbitopathy: increase in orbital fat is a rather late phenomenon. AB - AIM: To describe volumes of orbital fat (FV) and extraocular muscles (MV) in Graves' orbitopathy (GO) as a function of the duration of GO. PATIENTS: i) Cross sectional survey among 95 consecutive patients with untreated GO who had been referred to the combined thyroid-eye clinics of our university hospital. ii) Longitudinal survey among 39 of the 95 patients who did not receive any therapeutic intervention and were followed for 1 year. METHODS: A computed tomography (CT)-based and well-validated method for calculating orbital soft tissues. In order to neutralize sex differences, results are expressed as ratios of FV:orbital volume (OV) and MV:OV. RESULTS: i) Patients with GO duration of >1 year had greater FV:OV (0.65 vs 0.55, P=0.004), similar MV:OV (0.22 vs 0.21, not significant (NS)), and more proptosis (22 mm vs 21 mm, P=0.03) as compared to those with shorter duration. ii) As compared to baseline, after 1 year, FV:OV had increased (0.56 vs 0.63, P=0.000), MV:OV had not changed (0.19 vs 0.19, NS), proptosis was higher (20 mm vs 21 mm, P=0.003), and clinical activity scores had become lower (2 vs 1, P=0.02) (median values). CONCLUSION: CT images show that a longer duration of GO is associated with a higher orbital FV. Extraocular MV, however, is not associated with GO duration; rather, it is related to the severity of GO. PMID- 26142101 TI - High aromatase activity in hypogonadal men is associated with higher spine bone mineral density, increased truncal fat and reduced lean mass. AB - OBJECTIVE: Because the aromatase enzyme catalyzes the conversion of testosterone to estradiol (E2), the activity of this enzyme could be important in the musculoskeletal health of men with low testosterone. The objective of the present study is to determine the influence of aromatase activity on the bone mineral density (BMD) and body composition of patients with hypogonadism. DESIGN: Cross sectional study. METHODS: The baseline data of 90 patients between 40 and 74 years old who participated in a genetic study of response to testosterone therapy in men with low testosterone (i.e., <300 ng/dl) were analyzed. BMD and body composition were measured by dual-energy X-ray absorptiometry. Serum testosterone was measured by automated immunoassay, E2 was measured by ultrasensitive enzyme immunoassay, and sex hormone-binding globulin was measured by enzyme immunoassay. RESULTS: Men in the highest tertile of E2 to testosterone ratio (E2:T) had the highest spine BMD (P <= 0.037), highest truncal fat (P=0.046), and lowest truncal lean body mass (P=0.045). A similar pattern was observed in the upper extremities; that is, fat mass significantly increased (P=0.047), whereas lean mass significantly decreased (P=0.034) with increasing E2:T tertiles. CONCLUSION: The present findings suggest that in men with hypogonadism, aromatase activity could be an important determinant of musculoskeletal health. Men with high aromatase activity are able to maintain a higher BMD despite low circulating testosterone, but they have lower lean and higher truncal fat mass as compared to those with lower aromatase activity. PMID- 26142102 TI - Indices of adiposity and thyroid hormones in euthyroid postmenopausal women. AB - OBJECTIVE: We aimed to evaluate the association between thyroid hormones and indices of obesity in a sample of euthyroid postmenopausal women. DESIGN: Cross sectional study. METHODS: Serum levels of TSH, free triiodothyronine (FT3), and free thyroxine (FT4) as well as BMI and waist:hip ratio (WHR) were evaluated in 194 healthy euthyroid postmenopausal women. Ultrasonography was used to assess abdominal fat layers (subcutaneous fat (SF), preperitoneal fat (PF), and SF:PF ratio). Indices of adiposity were defined as high vs low depending on the median value of the assessed parameters. RESULTS: After multivariate adjustment for traditional risk factors, lower FT4 levels and a higher FT3:FT4 ratio predicted higher SF mass (FT4, Exp(beta)=0.035, P=0.020 and FT3:FT4, Exp(beta)=2.374, P=0.018), whereas higher FT3 predicted higher PF mass (Exp(beta)=2.815, P=0.032). Women with FT3:FT4 above the highest quartile had a significantly higher SF mass as compared to women in the lowest quartile (1.81 +/- 0.62 cm vs 1.54 +/- 0.46 cm, P=0.027). BMI had a positive independent association with TSH (Exp(beta)=1.829, P=0.018). Finally, FT3 was significantly associated with SF mass among women with higher BMI (FT3, beta=0.259, P=0.040) and women with higher WHR (beta=0.309, P=0.020) but not among women with lower BMI or WHR values. CONCLUSION: Thyroid hormone levels, and in particular FT3, were independently associated with SF and PF in euthyroid postmenopausal women, and this association was mainly evident in women with higher BMIs. On the other hand, among traditional indices of adiposity, only TSH was positively associated with BMI. Larger prospective studies are needed to evaluate the significance of the present findings. PMID- 26142103 TI - Which Patient Characteristics Among Cocaine Users with HIV Relate to Drug Use and Adherence Outcomes Following a Dual-Focused Intervention? AB - This is a secondary analysis of data from a randomized trial of dually-focused interventions for nonadherent HIV patients with cocaine use disorders (Ingersoll et al. in Drug Alcohol Depend 116(1-3):177-187, 2011). We examined the relationships among baseline demographic, psychological, psychiatric, and behavioral characteristics and 6-months post-study ART adherence, log viral load (VL), ASI Drug Composite Score, and days using cocaine. We used the SAS GLMSELECT procedure to build multivariate models of each post-study outcome. Post-study ART adherence was related to 2 psychological variables; while logVL was related to 2 drug-related behaviors. ASI Drug Composite score was related to 2 psychiatric disorders, 1 demographic, and 1 psychological variable; in contrast, days using cocaine related to 1 behavioral and 3 psychological variables. Analyses show clear, robust relationships among behavioral, psychological and psychiatric diagnosis factors with post-study ART adherence and cocaine use outcomes. Future ART adherence interventions for cocaine users should consider tailoring to these patient characteristics. PMID- 26142104 TI - Genome-wide analysis of the MYB gene family in physic nut (Jatropha curcas L.). AB - The MYB proteins comprise one of the largest transcription factor families in plants, and play key roles in regulatory networks controlling development, metabolism, and stress responses. A total of 125 MYB genes (JcMYB) have been identified in the physic nut (Jatropha curcas L.) genome, including 120 2R-type MYB, 4 3R-MYB, and 1 4R-MYB genes. Based on exon-intron arrangement of MYBs from both lower (Physcomitrella patens) and higher (physic nut, Arabidopsis, and rice) plants, we can classify plant MYB genes into ten groups (MI-X), except for MIX genes which are nonexistent in higher plants. We also observed that MVIII genes may be one of the most ancient MYB types which consist of both R2R3- and 3R-MYB genes. Most MYB genes (76.8% in physic nut) belong to the MI group which can be divided into 34 subgroups. The JcMYB genes were nonrandomly distributed on its 11 linkage groups (LGs). The expansion of MYB genes across several subgroups was observed and resulted from genome triplication of ancient dicotyledons and from both ancient and recent tandem duplication events in the physic nut genome. The expression patterns of several MYB duplicates in the physic nut showed differences in four tissues (root, stem, leaf, and seed), and 34 MYB genes responded to at least one abiotic stressor (drought, salinity, phosphate starvation, and nitrogen starvation) in leaves and/or roots based on the data analysis of digital gene expression tags. Overexpression of the JcMYB001 gene in Arabidopsis increased its sensitivity to drought and salinity stresses. PMID- 26142105 TI - The novel SNPs of leptin gene and their associations with growth traits in Chinese Nanjiang Yellow goat. AB - The leptin (LEP) gene encodes a protein that greatly affects the regulation of body weight, energy balance, and food intake in mammals. The objective of the present work was to identify genetic variants of the caprine LEP gene in 411 individuals from five Chinese goat breeds. Six novel single nucleotide polymorphisms (SNPs) (g.117T > C, g.1642G > A, g.2883G > A, g.3053T > C, g.3190G > A, and g.3314T > C) were detected using DNA sequencing. A chi-squared (chi(2)) test showed that all of the LEP SNPs were in Hardy-Weinberg equilibrium in the studied population (P > 0.05). Six common haplotypes were identified in the five goat populations, with frequencies ranging from 0.083 to 0.244. The r(2) linkage disequilibrium plot of the LEP SNPs indicated linkage disequilibrium only in the cultured breeds (NJ and JY). Statistical analysis revealed that all of the six SNPs of the LEP gene were associated with growth traits. The individuals with the GG genotype at g.1642G>A and g.3190G > A loci showed higher birth weight (2.38 +/ 0.03, 2.43 +/- 0.05) and weight at 2 months of age (10.59 +/- 0.16, 10.71 +/- 0.26) than the A-bearing genotypes (AA or GA, P < 0.05). Our findings indicate that polymorphisms of the caprine LEP gene might be important genetic factors influencing growth traits, and these genetic markers may be useful for future marker-assisted selection programs in goat breeding and production. PMID- 26142106 TI - Epistatic interaction between common AGT G(-6)A (rs5051) and AGTR1 A1166C (rs5186) variants contributes to variation in kidney size at birth. AB - Low nephron number has been recognised as an important cardiovascular risk factor and recently a strong correlation between renal mass and nephron number has been demonstrated in newborns. The aim of this study was to investigate individual, as well as combined, effects of common variants of genes which encode for major components of the renin-angiotensin system (REN G10601A, AGT G(-6)A, ACE I/D, AGTR1 A1166C) on kidney size in healthy, full-term newborns. A significant additive main effect of the ACE I/D polymorphism, as well as an additive-by additive interaction between AGT G(-6)A and AGTR1 A1166C variants, were found. The variance attributed to the epistatic effect was 27.9 ml(2)/m(4), which accounted for 73.8% of the interaction variance (37.8 ml(2)/m(4)), 66.4% of the genetic variance (42.0 ml(2)/m(4)) and 4.4% to the total phenotypic variance (628 ml(2)/m(4)). No other statistically significant main or epistatic effects were detected. Our results highlight the importance of considering gene-gene interactions as part of the genetic architecture of congenital nephron number, even when the loci do not show significant single locus effects. Unravelling the genetic determinants of low nephron number, along with early molecular screening, may well help to identify children at risk for cardiovascular disease. PMID- 26142107 TI - Impact of air pollutants from surface transport sources on human health: A modeling and epidemiological approach. AB - This study adopted an integrated 'source-to-receptor' assessment paradigm in order to determine the effects of emissions from passenger transport on urban air quality and human health in the megacity, Delhi. The emission modeling was carried out for the base year 2007 and three alternate (ALT) policy scenarios along with a business as usual (BAU) scenario for the year 2021. An Activity Structure-Emission Factor (ASF) framework was adapted for emission modeling, followed by a grid-wise air quality assessment using AERMOD and a health impact assessment using an epidemiological approach. It was observed that a 2021-ALT-III scenario resulted in a maximum concentration reduction of ~24%, ~42% and ~58% for carbon monoxide (CO), nitrogen dioxide (NO2) and particulate matter (PM), respectively, compared to a 2021-BAU scenario. Further, it results in significant reductions in respiratory and cardiovascular mortality, morbidity and Disability Adjusted Life Years (DALY) by 41% and 58% on exposure to PM2.5 and NO2 concentrations when compared to the 2021-BAU scenario, respectively. In other words, a mix of proposed policy interventions namely the full-phased introduction of the Integrated Mass Transit System, fixed bus speed, stringent vehicle emission norms and a hike in parking fees for private vehicles would help in strengthening the capability of passenger transport to cater to a growing transport demand with a minimum health burden in the Delhi region. Further, the study estimated that the transport of goods would be responsible for ~5.5% additional VKT in the 2021-BAU scenario; however, it will contribute ~49% and ~55% additional NO2 and PM2.5 concentrations, respectively, in the Delhi region. Implementation of diesel particulate filters for goods vehicles in the 2021-ALT IV-O scenario would help in the reduction of ~87% of PM2.5 concentration, compared to the 2021-BAU scenario; translating into a gain of 1267 and 505 DALY per million people from exposure to PM2.5 and NO2 concentrations, respectively. These findings suggest that significant health benefits are possible if goods transport is also included while designing strategies and policies in order to improve the overall urban air quality and minimize health impacts in city areas. PMID- 26142109 TI - The Prophylactic Mastectomy Dilemma: A Support Group for Women at High Genetic Risk for Breast Cancer. AB - The goal of this pilot study was to test the usefulness of a six session psychoeducational support group for women at high genetic risk for breast cancer who were considering prophylactic mastectomy. The themes of the group sessions included overestimation of and anxiety about risk; desire for "hard data"; the emotional impact of watching a mother die of breast cancer; concerns about spouse reactions; self- and body image; the decision-making process; and confusion over whom to trust in decision making. Both the participants and the multidisciplinary leaders concluded that as a supplement to individual counseling, a support group is a beneficial and cost-effective treatment modality. Recommendations for the optimal format for such a group are described. PMID- 26142110 TI - Genetic Library. PMID- 26142108 TI - Update and Review: Cystic Fibrosis. AB - Cystic fibrosis (CF) is one of the most commonly inherited recessive disorders in U.S. Caucasians, with a carrier frequency of approximately 1 in 29. Genetic counseling and CF mutation analysis has traditionally been offered to the affected patient and his/her extended family, in keeping with policy statements from professional organizations (ASHG, NSGC, ACOG). The target population for CF testing and counseling may be evolving after the release of the 1997 National Institutes of Health Consensus Statement, Genetic Testing for Cystic Fibrosis, which recommends that CF screening be offered to all preconceptional and pregnant couples. Genetic counseling for CF is complicated by reports of polymorphisms in the CF gene that are associated with symptoms that do not meet the diagnostic criteria for CF, such as bilateral congenital absence of the vas deferens, bronchiectasis, and idiopathic pancreatitis. To aid genetic counselors with these issues, this review explores the symptoms of CF, patient management, gene function, genetics, genotype/phenotype correlation, and genetic counseling issues. PMID- 26142111 TI - Closed-loop controller for chest compressions based on coronary perfusion pressure: a computer simulation study. AB - High-quality cardiopulmonary resuscitation contributes to cardiac arrest survival. The traditional chest compression (CC) standard, which neglects individual differences, uses unified standards for compression depth and compression rate in practice. In this study, an effective and personalized CC method for automatic mechanical compression devices is provided. We rebuild Charles F. Babbs' human circulation model with a coronary perfusion pressure (CPP) simulation module and propose a closed-loop controller based on a fuzzy control algorithm for CCs, which adjusts the CC depth according to the CPP. Compared with a traditional proportion-integration-differentiation (PID) controller, the performance of the fuzzy controller is evaluated in computer simulation studies. The simulation results demonstrate that the fuzzy closed-loop controller results in shorter regulation time, fewer oscillations and smaller overshoot than traditional PID controllers and outperforms the traditional PID controller for CPP regulation and maintenance. PMID- 26142113 TI - Response to letter by Boeker et al. Development of search strategies for systematic reviews: further issues regarding the objective and conceptual approaches. PMID- 26142112 TI - Volumetric quantitative characterization of human patellar cartilage with topological and geometrical features on phase-contrast X-ray computed tomography. AB - Phase-contrast X-ray computed tomography (PCI-CT) has attracted significant interest in recent years for its ability to provide significantly improved image contrast in low absorbing materials such as soft biological tissue. In the research context of cartilage imaging, previous studies have demonstrated the ability of PCI-CT to visualize structural details of human patellar cartilage matrix and capture changes to chondrocyte organization induced by osteoarthritis. This study evaluates the use of geometrical and topological features for volumetric characterization of such chondrocyte patterns in the presence (or absence) of osteoarthritic damage. Geometrical features derived from the scaling index method (SIM) and topological features derived from Minkowski Functionals were extracted from 1392 volumes of interest (VOI) annotated on PCI-CT images of ex vivo human patellar cartilage specimens. These features were subsequently used in a machine learning task with support vector regression to classify VOIs as healthy or osteoarthritic; classification performance was evaluated using the area under the receiver operating characteristic curve (AUC). Our results show that the classification performance of SIM-derived geometrical features (AUC: 0.90 +/- 0.09) is significantly better than Minkowski Functionals volume (AUC: 0.54 +/- 0.02), surface (AUC: 0.72 +/- 0.06), mean breadth (AUC: 0.74 +/- 0.06) and Euler characteristic (AUC: 0.78 +/- 0.04) (p < 10(-4)). These results suggest that such geometrical features can provide a detailed characterization of the chondrocyte organization in the cartilage matrix in an automated manner, while also enabling classification of cartilage as healthy or osteoarthritic with high accuracy. Such features could potentially serve as diagnostic imaging markers for evaluating osteoarthritis progression and its response to different therapeutic intervention strategies. PMID- 26142114 TI - Multivariate meta-analysis of individual participant data helped externally validate the performance and implementation of a prediction model. AB - OBJECTIVES: Our aim was to improve meta-analysis methods for summarizing a prediction model's performance when individual participant data are available from multiple studies for external validation. STUDY DESIGN AND SETTING: We suggest multivariate meta-analysis for jointly synthesizing calibration and discrimination performance, while accounting for their correlation. The approach estimates a prediction model's average performance, the heterogeneity in performance across populations, and the probability of "good" performance in new populations. This allows different implementation strategies (e.g., recalibration) to be compared. Application is made to a diagnostic model for deep vein thrombosis (DVT) and a prognostic model for breast cancer mortality. RESULTS: In both examples, multivariate meta-analysis reveals that calibration performance is excellent on average but highly heterogeneous across populations unless the model's intercept (baseline hazard) is recalibrated. For the cancer model, the probability of "good" performance (defined by C statistic >=0.7 and calibration slope between 0.9 and 1.1) in a new population was 0.67 with recalibration but 0.22 without recalibration. For the DVT model, even with recalibration, there was only a 0.03 probability of "good" performance. CONCLUSION: Multivariate meta-analysis can be used to externally validate a prediction model's calibration and discrimination performance across multiple populations and to evaluate different implementation strategies. PMID- 26142115 TI - The indication area of a diagnostic test. Part II--the impact of test dependence, physician's decision strategy, and patient's utility. AB - OBJECTIVES: Any diagnostic test has an indication area of prior probabilities wherein the gain in diagnostic certainty outweighs its loss. Here, we investigate whether indication area and the maximum diagnostic gain are robust measures if we assume test dependence, alternative physician's heuristics, and varying patient's utilities. STUDY DESIGN AND SETTING: Three mathematical functions for the dependence of test sensitivity (Se) and specificity (Sp) on the prior disease probability were studied. In addition, three different decision heuristics for further management were explored for the case that "no test" would be done. Finally, the valuation of test outcomes was varied. A sensitivity analysis was performed to determine the impact of the alternative assumptions on the indication area and maximum diagnostic gain. RESULTS: By assuming test dependence, the indication area shifts to higher priors and increases the maximum diagnostic gain. Decision strategies assuming a "threshold before treat" can inadvertently widen the indication area and increase the maximum diagnostic gain. Varying patient utilities will usually reduce the net diagnostic gain. A sensitivity analysis revealed the robustness of the model. CONCLUSION: The indication area and the maximum diagnostic gain are robust measures of test performance and are easier to interpret than the classical performance measures. PMID- 26142117 TI - Short-term follow-up of digital ulcers by laser speckle contrast analysis in systemic sclerosis patients. AB - OBJECTIVE: To monitor in systemic sclerosis (SSc) the evolution of digital ulcer (DU) status by analysing blood perfusion (BP) using laser speckle contrast analysis (LASCA). METHODS: Hand BP was recorded by LASCA in twenty SSc patients with recent onset fingertip DUs before and after 10days of local/systemic treatment. Regions of interest (ROIs) to analyse BP were created al the level of ulcer, peri-ulcer, periungual and fingertip areas. Visual analogue pain scale (VAS) was also administered to patients before and after follow-up. RESULTS: A statistically significant increase of BP was observed from T0 to T1 in the ROIs created at the level of the ulcer area (p<0.0001), as well as a significant decrease of BP was observed in the peri-ulcer area (p<0.0001). A statistically significant decrease of both ulcer size (p<0.0001) and VAS (p=0.001) was observed, whereas no significant variation of both periungual and fingertip BP was detected. CONCLUSIONS: LASCA may safely monitor DU evolution in SSc patients, by evaluating its blood perfusion and area during standard treatment. This may be useful to monitor DU evolution during treatment in clinical trials. PMID- 26142118 TI - Detecting microvascular changes in the mouse spleen using optical computed tomography. AB - Methods of monitoring drug toxicity in off-target organs are very important in the development of effective and safe drugs. Standard 2-D techniques, such as histology, are prone to sampling errors and can miss important information. We demonstrate a novel application of optical computed tomography (CT) imaging to quantitatively assess, in 3-D, the response of adult murine spleen to off-target drug toxicity induced by treatment with the vascular disrupting agent ZD6126. Reconstructed images from optical CT scans sensitive to haemoglobin absorption reveal detailed, high-contrast 3-D maps of splenic structure and microvasculature. A significant difference in total splenic volume was found between vehicle and ZD6126-treated cohorts, with mean volumes of 61+/-3mm(3) and 44+/-3mm(3) respectively (both n=3, p=0.05). Textural statistics for each sample were calculated using grey-level co-occurrence matrices (GLCMs). Standard 2-D GLCM analysis was found to be slice-dependent while 3-D GLCM contrast and homogeneity analysis resulted in separation of the vehicle and ZD6126-treated cohorts over a range of length scales. PMID- 26142119 TI - In Vitro Exposure of Harbor Seal Immune Cells to Aroclor 1260 Alters Phocine Distemper Virus Replication. AB - In the last 30 years, several large-scale marine mammal mortality events have occurred, often in close association with highly polluted regions, leading to suspicions that contaminant-induced immunosuppression contributed to these epizootics. Some of these recent events also identified morbillivirus as a cause of or contributor to death. The role of contaminant exposures regarding morbillivirus mortality is still unclear. The results of this study aimed to address the potential for a mixture of polychlorinated biphenyls (PCBs), specifically Aroclor 1260, to alter harbor seal T-lymphocyte proliferation and to assess if exposure resulted in increased likelihood of phocine distemper virus (PDV USA 2006) to infect susceptible seals in an in vitro system. Exposure of peripheral blood mononuclear cells to Aroclor 1260 did not significantly alter lymphocyte proliferation (1, 5, 10, and 20 ppm). However, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), lymphocytes exposed to 20 ppm Aroclor 1260 exhibited a significant decrease in PDV replication at day 7 and a significant increase at day 11 compared with unexposed control cells. Similar and significant differences were apparent on exposure to Aroclor 1260 in monocytes and supernatant. The results here indicate that in harbor seals, Aroclor 1260 exposure results in a decrease in virus early during infection and an increase during late infection. The consequences of this contaminant-induced infection pattern in a highly susceptible host could result in a greater potential for systemic infection with greater viral load, which could explain the correlative findings seen in wild populations exposed to a range of persistent contaminants that suffer from morbillivirus epizootics. PMID- 26142116 TI - Galectin-3 in autoimmunity and autoimmune diseases. AB - Galectin-3 (gal-3) is a beta-galactoside-binding lectin, which regulates cell cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. PMID- 26142120 TI - Organohalogen Contaminants and Vitamins in Northern Fur Seals (Callorhinus ursinus) Collected During Subsistence Hunts in Alaska. AB - During native subsistence hunts from 1987 to 2007, blubber and liver samples from 50 subadult male northern fur seals (Callorhinus ursinus) were collected on St. Paul Island, Alaska. Samples were analyzed for legacy persistent organic pollutants (POPs), recently phased-out/current-use POPs, and vitamins. The legacy POPs measured from blubber samples included polychlorinated biphenyl congeners, DDT (and its metabolites), chlorobenzenes, chlordanes, and mirex. Recently phased out/current-use POPs included in the blubber analysis were the flame retardants, polybrominated diphenyl ethers, and hexabromocyclododecanes. The chemical surfactants, perfluorinated alkyl acids, and vitamins A and E were assessed in the liver samples. Overall, concentrations of legacy POPs are similar to levels seen in seal samples from other areas of the North Pacific Ocean and the Bering Sea. Statistically significant correlations were seen between compounds with similar functions (pesticides, flame retardants, vitamins). With sample collection spanning two decades, the temporal trends in the concentrations of POPs and vitamins were assessed. For these animals, the concentrations of the legacy POPs tend to decrease or stay the same with sampling year; however, the concentrations of the current-use POPs increased with sampling year. Vitamin concentrations tended to stay the same across the sampling years. With the population of northern fur seals from St. Paul Island on the decline, a detailed assessment of exposure to contaminants and the correlations with vitamins fills a critical gap for identifying potential population risk factors that might be associated with health effects. PMID- 26142122 TI - Transplacental Transfer of Polychlorinated Biphenyls, Polybrominated Diphenylethers, and Organochlorine Pesticides in Ringed Seals (Pusa hispida). AB - The transplacental transfer of persistent organic pollutants in marine mammals takes place at a formative developmental period, thereby exposing the fetus to endocrine-disrupting compounds. We evaluated the transplacental transfer of polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs), and organochlorine pesticides (OCPs) in five pregnant ringed seals in Northern Labrador, Canada. PCBs, PBDEs, and OCPs were transferred from the mother to the fetus with average concentrations in the fetuses ranging from 0.3 ng/g lipid weight (lw) of mirex to 94 ng/g lw of PCBs. The average percent transferred to the blubber in the fetus was very low with <0.02 % for each of the compounds studied. Based on relationships observed, transfer for full-term fetuses is estimated to range from 0.03 to 0.27 %. Log K(ow) explained the transfer of PCBs (r (2) = 0.67, p < 0.001) and OCPs (r (2) = 0.62, p < 0.001) with those PCB congeners and OCP compounds having a log K(ow) of <6.0 and 4.6, respectively, because they are preferentially transferred to the fetus. Adult females transferred a contaminant mixture to their fetuses, which correlated with estimated fetal age (p < 0.001; r (2) = 0.697), with younger fetuses showing a greater proportion of compounds with low K(ow) compared with later-term fetuses. The implications for the prenatal exposure to these developmental toxicants remains unknown because current toxicity thresholds in marine mammals have only been derived from juveniles or adults. PMID- 26142121 TI - Toxicity Persistence of Chlorpyrifos in Runoff from Experimental Soybean Plots to the Non-target Amphipod Hyalella curvispina: Effect of Crop Management. AB - Toxicity persistence to the nontarget amphipod Hyalella curvispina in runoff events following chlorpyrifos applications to soy experimental plots was compared in conventional and no-till management. Two application scenarios were compared: an early-season application with the soil almost bare and a late-season application after the foliage had attained complete soil cover. H. curvispina was exposed to chlorpyrifos using two different test systems: a short-term (48 h) runoff water exposure and a long-term (10 days) soil exposure. Both commonly used crop management practices for soybean production resulted in runoff toxicity following pesticide applications and represent a toxicity risk for adjacent inland waters. Toxicity persistence was longer after the earlier than the late season application, likely because of higher volatilization and photodecomposition losses from the soy canopy than from the soil. For the early season application, toxicity persisted longer in the no-till plots than in the conventional tillage plots. Suspended matter was higher in the conventional treatment. Chlorpyrifos sorption to suspended matter likely contributed to the shorter persistence. For the late-season application, toxicity persisted longer in the conventional treatment. The causes remain conjectural. The soil organic carbon content was higher in the no-till treatment. Sorption to organic matter might have contributed to the shorter chlorpyrifos toxicity persistence in no till management. Late applications are more frequent and prevail longer throughout the soy growing season. Overall, the no-till management practice seems preferably because shorter toxicity persistence in runoff represents a lower environmental risk for the adjacent inland waters. PMID- 26142123 TI - The Single-Incision Sling to Treat Female Stress Urinary Incontinence: A Dynamic Computational Study of Outcomes and Risk Factors. AB - Dynamic behaviors of the single-incision sling (SIS) to correct urethral hypermobility are investigated via dynamic biomechanical analysis using a computational model of the female pelvis, developed from a female subject's high resolution magnetic resonance (MR) images. The urethral hypermobility is simulated by weakening the levator ani muscle in the pelvic model. Four positions along the posterior urethra (proximal, midproximal, middle, and mid-distal) were considered for sling implantation. The alpha-angle, urethral excursion angle, and sling-urethra interaction force generated during Valsalva maneuver were quantitatively characterized to evaluate the effect of the sling implantation position on treatment outcomes and potential complications. Results show concern for overcorrection with a sling implanted at the bladder neck, based on a relatively larger sling-urethra interaction force of 1.77 N at the proximal implantation position (compared with 0.25 N at mid-distal implantation position). A sling implanted at the mid-distal urethral location provided sufficient correction (urethral excursion angle of 23.8 deg after mid-distal sling implantation versus 24.4 deg in the intact case) with minimal risk of overtightening and represents the optimal choice for sling surgery. This study represents the first effort utilizing a comprehensive pelvic model to investigate the performance of an implanted sling to correct urethral hypermobility. The computational modeling approach presented in the study can also be used to advance presurgery planning, sling product design, and to enhance our understanding of various surgical risk factors which are difficult to obtain in clinical practice. PMID- 26142124 TI - C9orf72 hexanucleotide repeat expansions in Chinese sporadic amyotrophic lateral sclerosis. AB - A hexanucleotide repeat expansion (HRE) in the C9orf72 gene has been identified as the most common mutation in amyotrophic lateral sclerosis (ALS) among Caucasian populations. We sought to comprehensively evaluate genetic and epigenetic variants of C9orf72 and the contribution of the HRE in Chinese ALS cases. We performed fragment-length and repeat-primed polymerase chain reaction to determine GGGGCC copy number and expansion within the C9orf72 gene in 1092 sporadic ALS (sALS) and 1062 controls from China. We performed haplotype analysis of 23 single-nucleotide polymorphisms within and surrounding C9orf72. The C9orf72 HRE was found in 3 sALS patients (0.3%) but not in control subjects (p = 0.25). For 2 of the cases with the HRE, genotypes of 8 single-nucleotide polymorphisms flanking the HRE were inconsistent with the haplotype reported to be strongly associated with ALS in Caucasian populations. For these 2 individuals, we found hypermethylation of the CpG island upstream of the repeat, an observation not detected in other sALS patients (p < 10(-8)) or controls. The detailed analysis of the C9orf72 locus in a large cohort of Chinese samples provides robust evidence that may not be consistent with a single Caucasian founder event. Both the Caucasian and Chinese haplotypes associated with HRE were highly associated with repeat lengths >8 repeats implying that both haplotypes may confer instability of repeat length. PMID- 26142125 TI - Serum microRNAs in sporadic amyotrophic lateral sclerosis. AB - MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and specific mircoRNA "fingerprints" are thought to contribute to and/or reflect certain disease conditions. Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations. Here, we characterize circulating miRNAs in the serum of sporadic ALS patients. We show that, in contrast to familial ALS, miRNA signatures of sporadic ALS are highly heterogeneous suggesting a number of different etiologies. Nevertheless, 2 miRNAs, miR-1234-3p and miR-1825, could be identified to be consistently downregulated in sporadic ALS. Bioinformatic analysis revealed miRNA fingerprints resembling those of familial ALS patients and mutation carriers in 61% of sporadic ALS patients, while the remaining subgroup had clearly different miRNA signatures. These data support a higher than expected contribution of genetic factors also to sporadic ALS. Moreover, our results indicate a more heterogeneous molecular etiology of sporadic ALS compared with (mono)genic cases, which should be considered for the development of disease modifying treatments. PMID- 26142127 TI - Approaching Complex Cases With a Crisis Intervention Model and Teamwork. AB - Patients referred for genetic counseling may be in a state of crisis, feeling as though they are incapable of making decisions about the management of their pregnancy, genetic testing options and/or life planning issues. The role of the genetic counselor is to assist a patient through this crisis state by increasing the patient's understanding and by helping to facilitate decision making and adjustment to those decisions. In this paper we present a clinical genetic counseling case that was complicated by numerous medical and psychosocial issues. The wide scope of this case required the involvement of both a prenatal and a medical genetic counselor. Working as a team we utilized a crisis intervention model. Our counseling focused on identifying and isolating the issues, providing factual information, setting a time frame for decisions to be made, and encouraging social support and emotion-focused coping strategies. PMID- 26142126 TI - Effect of long-term treatment with rasagiline on cognitive deficits and related molecular cascades in aged mice. AB - The present study aimed to investigate the protective effects of prolonged treatment with the selective, irreversible monoamine oxidase-B inhibitor, novel anti-parkinsonian drug, rasagiline (Azilect) in aged animals. Our findings from behavioral experiments demonstrated that long-term treatment of aged mice with rasagiline (0.2 mg/kg) exerted significant beneficial effects on mood-related dysfunction and spatial learning and memory functions. At this dose of rasagiline, chronic drug administration significantly inhibited monoamine oxidase B activity and caused an increase in striatal dopamine and serotonin levels, while decreasing their metabolism. In addition, rasagiline treatment elevated striatal mRNA expression levels of dopamine receptors D1 and D2. Furthermore, we found that rasagiline upregulated expression levels of the synaptic plasticity markers brain-derived neurotrophic factor, tyrosine kinase-B receptor, and synapsin-1, increased Bcl-2 to Bax antiapoptotic ratio and the activity of the antioxidant enzyme, catalase in brain of aged mice. The present study demonstrated that long-term treatment with rasagiline could affect behavioral deficits in aged mice and upregulate various neuroprotective parameters in the aging brain, indicating that the drug may have therapeutic potential for treatment of age-associated neurodegenerative disorders. PMID- 26142128 TI - Approaching Complex Cases With a Crisis Intervention Model and Teamwork: A Commentary. AB - This article is a response to the case of SA presented by O'Daniel and Wells. In this response I support the approach used with the patient, and discuss and expand on the applicability of a crisis intervention model to genetic counseling. In addition, I explore the issue of autonomy and informed decision making for patients who are in crisis. I also discuss the surface contradiction between the mandate for nondirectiveness and the need to provide direction during crisis intervention are discussed and reframe the issue as one of process versus content directiveness. I argue that during times of crisis, genetic counselors may need to direct process in order for patients to be able to make autonomous decisions. PMID- 26142129 TI - Factors Influencing Men's Interest in Gene Testing for Prostate Cancer Susceptibility. AB - Interest in genetic testing for inherited cancer susceptibility is high in the general population. Women at risk for BRCA1 and BRCA2 mutations represent the best-studied population undergoing genetic testing for cancer susceptibility. However, it is unclear whether factors influencing interest in genetic testing in women are directly applicable to men. We designed a study to examine factors associated with men's interest in genetic testing to identify prostate cancer susceptibility. Our sample consisted of 267 men present in waiting rooms of a urology clinic in an urban area. We examined whether the concept of "monitoring" could be used to predict the interest of men in a genetic test for prostate cancer susceptibility. Our results indicated that "monitoring" trait was positively associated with interest in genetic testing in these men, but principally for patients rather than nonpatients. Moreover we found that monitoring was associated with over estimation of risk in those men with prostate cancer. Other factors found to influence interest in genetic testing included recommendation by a doctor, family history of prostate cancer, and cost. This study indicated that interest in genetic testing and estimation of risk is influenced by a complex interaction between both psychological factors (monitoring) and nonbehavioral factors (such as patient status, cost, and doctor recommendation). PMID- 26142130 TI - Guidelines for Writing Letters to Patients. AB - Patient letters provide a permanent record of the genetic counseling that was provided and are unique in medical care; rarely do other health care providers send summaries written specifically to their patients and families. We surveyed genetic counseling training program directors and found that while the acquisition of patient letter-writing skills was considered important, there were no specific guidelines made available to students. To develop letter-writing guidelines, we evaluated patient letters, reviewed references on professional correspondence, surveyed the medical literature, and worked with a writing consultant. The guidelines we subsequently developed and present here include a format for writing patient letters, suggestions on presenting medical information in understandable terms, and wording considerations. These patient letter-writing guidelines are intended to serve as a guide for teaching students this important skill and as a resource for practicing health care professionals. PMID- 26142131 TI - Commentary on Guidelines for Writing Letters to Patients. PMID- 26142132 TI - Letter to the Editor: Thomas Hodgkin on the Marriage of First Cousins. PMID- 26142134 TI - Letter to the Editor. PMID- 26142133 TI - Letter to the Editor: Consanguinity and Congenital Birth Defects. PMID- 26142135 TI - Letter to the Editor: Reply to Becker and Morgan. PMID- 26142136 TI - Genetic Library: Cancer Genetics. PMID- 26142140 TI - Adherence to oral anticancer chemotherapy: What influences patients' over or non adherence? Analysis of the OCTO study through quantitative-qualitative methods. AB - BACKGROUND: Numerous oral anticancer chemotherapies are available. Non-adherence or over-adherence to these chemotherapies can lead to lowered efficacy and increased risk of adverse events. The objective of this study was to identify patients' adherence profiles using a qualitative-quantitative method. METHODS: A capecitabine treatment was initiated for 38 patients with advanced breast or colorectal cancer. At inclusion, information on patients' beliefs was reported using a questionnaire. Later, Information on patients' relation to treatment was obtained from a sub-group during an interview with a sociologist. Questionnaires were analyzed using Multiple Classification Analysis to cluster patients. Treatment adherence was evaluated by an electronic medication event monitoring systems (MEMS caps) and then correlated with patient clusters. Interviews were analyzed to complete and explain results. RESULTS: 38 patients were enrolled between 2008 and 2011 and completed the questionnaire. Twenty had adherence measured with MEMS caps all along treatment. Between 4 and 6 months after inclusion, 16 patients were interviewed. Patient profile B (retired, with a regular life, surrounded by a relative's attention to drug adherence, with a low educational level) was statistically associated with adequate adherence (p = 0.049). A tendency for lower adherence was observed among more highly educated patients with an irregular, active life (NS). All patients taking capecitabine demonstrated a risk of over-adherence, potentiating side effects. CONCLUSIONS: These encouraging primary results suggest that further studies should be undertaken and that educational programs tailored to patient profiles should be evaluated to enhance adherence for those who need it and to empower all patients to manage treatment side effects. PMID- 26142142 TI - A study of the role of glucose transporter 1 (Glut1) in white spot syndrome virus (WSSV) infection. AB - White spot syndrome virus (WSSV) is a large enveloped DNA virus, and it causes a serious disease that has led to severe mortalities of cultured shrimps in many countries. To determine the mechanism of virus entry into the cell and to establish an antiviral strategy, the cell receptor for virus entry and receptor binding protein should be identified. A shrimp cell surface protein, glucose transporter1 (Glut1), was found to interact with WSSV in previous study. In this study, this Glut1 was confirmed to have the ability of transporting glucose, and this gene can also be found in other shrimp species. The interaction between Glut1 and some other WSSV envelope proteins in the infectome structure was verified by far western blot and His pull down assay. In vitro and in vivo neutralization using recombinant partial Glut1 revealed that the large extracellular portion of Glut1 could delay WSSV infection. Also, shrimps which were knocked-down Glut1 gene by treated with dsRNA before WSSV challenge showed decreased mortality. These results indeed provide a direction to develop efficient antiviral strategies or therapeutic methods by using Glut1. PMID- 26142141 TI - Practice Parameter for Interventional Clinical Practice and Management. PMID- 26142143 TI - Oxidative stress response of the black tiger shrimp Penaeus monodon to Vibrio parahaemolyticus challenge. AB - Vibrio parahaemolyticus is a virulent pathogen that affects shrimp aquaculture. Reactive oxygen species are produced by the immune system that defends the host against foreign microorganisms. In the present study, the oxidative stress response in hepatopancreas and gills of Penaeus monodon to V. parahaemolyticus challenge were studied, such as respiratory burst, ROS production (.O2(-) and .OH), activities of antioxidant enzymes (CAT, GPx, SOD, POD and GST) and oxidative damage to lipid and protein (indexed by contents of MDA). Compared with the control group, after V. parahaemolyticus challenge, respiratory burst and ROS production were up-regulated significantly. GPx and POD activity increased significantly in hepatopancreas and gills of the shrimps at 12 h, but CAT activity decreased markedly at 12 h and 24 h. SOD and GST activity in hepatopancreas of the shrimps increased significantly at 1.5 h, but decreased markedly at 12 h-48 h. MDA content increased significantly after 6 h-24 h challenge. HE staining showed that V. parahaemolyticus challenge induced damage symptoms in hepatopancreas of P. monodon. Our study revealed that V. parahaemolyticus influenced the antioxidative status and caused oxidative stress and tissue damage via confusion of antioxidant enzymes in P. monodon. PMID- 26142147 TI - Understanding public perceptions of biotechnology through the "Integrative Worldview Framework". AB - Biotechnological innovations prompt a range of societal responses that demand understanding. Research has shown such responses are shaped by individuals' cultural worldviews. We aim to demonstrate how the Integrative Worldview Framework (IWF) can be used for analyzing perceptions of biotechnology, by reviewing (1) research on public perceptions of biotechnology and (2) analyses of the stakeholder-debate on the bio-based economy, using the Integrative Worldview Framework (IWF) as analytical lens. This framework operationalizes the concept of worldview and distinguishes between traditional, modern, and postmodern worldviews, among others. Applied to these literatures, this framework illuminates how these worldviews underlie major societal responses, thereby providing a unifying understanding of the literature on perceptions of biotechnology. We conclude the IWF has relevance for informing research on perceptions of socio-technical changes, generating insight into the paradigmatic gaps in social science, and facilitating reflexive and inclusive policy-making and debates on these timely issues. PMID- 26142145 TI - Human campylobacteriosis related to the consumption of raw milk sold by vending machines in Italy: Quantitative risk assessment based on official controls over four years. AB - A quantitative risk assessment (RA) model was developed to describe the risk of campylobacteriosis linked to consumption of raw milk sold in vending machines in Italy. Exposure assessment was based on the official microbiological records of raw milk samples from vending machines monitored by the regional Veterinary Authorities from 2008 to 2011, microbial growth during storage, destruction experiments, consumption frequency of raw milk, serving size, consumption preference and age of consumers. The differential risk considered milk handled under regulation conditions (4 degrees C throughout all phases) and the worst time-temperature field handling conditions detected. Two separate RA models were developed, one for the consumption of boiled milk and the other for the consumption of raw milk, and two different dose-response (D-R) relationships were considered. The RA model predicted no human campylobacteriosis cases per year either in the best (4 degrees C) storage conditions or in the case of thermal abuse in case of boiling raw milk, whereas in case of raw milk consumption the annual estimated campylobacteriosis cases depend on the dose-response relationships used in the model (D-R I or D-R II), the milk time-temperature storage conditions, consumer behaviour and age of consumers, namely young (with two cut-off values of <=5 or <=6 years old for the sensitive population) versus adult consumers. The annual estimated cases for young consumers using D-R II for the sensitive population (<=5 years old) ranged between 1013.7/100,000 population and 8110.3/100,000 population and for adult consumers using D-R I between 79.4/100,000 population and 333.1/100,000 population. Quantification of the risks associated with raw milk consumption is necessary from a public health perspective and the proposed RA model represents a useful and flexible tool to perform future RAs based on local consumer habits to support decision-making on safety policies. Further educational programmes for raw milk consumers or potential raw milk consumers are required to encourage consumers to boil milk to reduce the associated risk of illness. PMID- 26142144 TI - Identification and expression analysis of nascent polypeptide-associated complex alpha gene in response to immune challenges in Japanese flounder Paralichthys olivaceus. AB - Nascent polypeptide-associated complex (NAC) is a conserved heterodimeric protein consisting of alpha and beta subunits. In addition to acting as a protein translation chaperone by forming a heterodimer with the beta subunit, NAC alpha (NACA) also shows important immune significance independent of NAC beta in mammalian cells. In lower vertebrates, however, the immunological relevance of NACA has not been revealed yet. In the present study, we identified and characterized a NACA gene (termed poNACA) involved in innate immune response in Japanese flounder Paralichthys olivaceus. poNACA encodes a 215-amino-acid protein, with an apparent molecular weight of 23.5 kDa and an isoelectric point of 4.51. Tissue distribution analysis revealed that poNACA gene was constitutively expressed in all examined tissues and showed dominant expression in hepatopancreas and gonad tissues. In enriched Japanese flounder head kidney macrophages and peripheral blood leucocytes, the expression of poNACA mRNA transcript was significantly induced by LPS, Poly(I:C) and zymosan stimulations. In vivo experiments further revealed that poNACA gene expression was up-regulated in head kidney, gill and spleen tissues in response to Edwardsiella tarda challenges. Furthermore, overexpression of poNACA in Japanese flounder FG-9307 cells resulted in increased gene expression of IL-1beta, IL-11 and TNF-alpha, and myxovirus resistance (Mx). Taken together, our findings indicate that an immune response gene, poNACA, involved in innate immune regulation in P. olivaceus has been identified. PMID- 26142148 TI - Global warming's five Germanys: A typology of Germans' views on climate change and patterns of media use and information. AB - People's attitudes toward climate change differ, and these differences may correspond to distinct patterns of media use and information seeking. However, studies extending analyses of attitude types and their specific media diets to countries beyond the United States are lacking. We use a secondary analysis of survey data from Germany to identify attitudes toward climate change among the German public and specify those segments of the population based on their media use and information seeking. Similar to the Global Warming's Six Americas study, we find distinct attitudes (Global Warming's Five Germanys) that differ in climate change-related perceptions as well as in media use and communicative behavior. These findings can help tailor communication campaigns regarding climate change to specific audiences. PMID- 26142149 TI - Off-pump bilateral skeletonized internal thoracic artery grafting in patients with chronic kidney disease. AB - BACKGROUND: We compared the outcomes in propensity score-matched patients who had chronic kidney disease (CKD) undergoing off-pump coronary bypass grafting, with either a bilateral or single skeletonized internal thoracic artery (ITA). METHODS: Of 1254 consecutive patients undergoing isolated coronary bypass surgery (1248 by the off-pump technique without emergent conversion to cardiopulmonary bypass), the 1203 who received a skeletonized, single (n = 453) or bilateral (n = 750), ITA graft were enrolled, after excluding the 6 patients who received preoperative percutaneous cardiopulmonary support and the 75 who had only 1 target vessel in the left coronary area. A total of 412 pairs were matched using propensity scores. Kaplan-Meier analyses were used to assess all-cause and cardiac-related mortality, by CKD stage (assessed by glomerular filtration rate [GFR]: <30; 30-60; >60 mL/minute/1.73 m(2)). Multivariate Cox proportional hazard models were used to assess for association of bilateral grafting with mortality. A test for interaction of bilateral ITA grafting and estimated GFR was conducted. RESULTS: No significant difference was found in the incidence of 30-day mortality, stroke, or deep sternal infection between the 2 groups. Although an advanced stage of CKD decreased overall survival, a benefit of bilateral ITA grafting for all-cause and cardiac-related mortality occurred relatively early in the follow-up period and was not influenced by CKD stage. Bilateral ITA grafting was independently associated with a lower risk of both all-cause and cardiac related mortality in patients with an estimated GFR of <60. No interaction was found between bilateral ITA grafting and estimated GFR in either model. CONCLUSIONS: In patients who have CKD, off-pump, skeletonized, left-side bilateral ITA grafting is associated with lower risk of all-cause and cardiac related mortality, and does not increase operative risk. PMID- 26142150 TI - Erratum to: Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. PMID- 26142152 TI - Do Platelets Inhibit the Effect of Aspirin on Cancer Cells? AB - Both platelets and cancer cells display an intimate reciprocal crosstalk resulting in alteration of each other's properties. Although many past studies have tried to demonstrate effect of platelets on tumour cells, exact role of platelets in carcinogenesis is still not clear. In the above study, we explored the effect of different concentrations of platelet rich plasma (PRP) on viability, proliferation and adhesion of HeLa cells in culture conditions. The above parameters were found to be slightly increased on incubation with lower two concentrations of PRP (4.4 * 10(5) & 1 * 10(6) platelets/MUl) while a reverse effect was seen at high PRP concentration (2 * 10(6) lac platelets/MUl) especially at 24 h. To further validate that the above effects were due to platelets we repeated the experiments in the presence of antiplatelet drug aspirin (20 mM). On treatment with aspirin alone, the cell viability, proliferation and adhesion were seen to be decreased indicating cytotoxicity of aspirin towards HeLa cells. However, all of the above parameters were found to increase on addition of all PRP concentrations at 24 h. Overall, variations in the number of platelets produced different effects on the cancer cells. Use of aspirin reduced the viability of the cancer cells, but this effect was seen to be partially reversed by all the concentrations of PRP used. PMID- 26142151 TI - Effect of ageing on keratoconic corneas. AB - PURPOSE: To explore the potential effect of ageing on the corneal curvature and corrected visual acuity in patients with long-term keratoconus because of the paucity of these patients older than 50 years. METHODS: Records of keratoconic patients, who had initially presented to a specialized contact lens clinic and followed for more than 20 years after disease onset, were reviewed. Collected information included age, gender, date of first and last examination, date of onset of the disease, central corneal curvature, refraction, best corrected visual acuity (BCVA), therapeutic modality and clinical signs. RESULTS: Age of patients at last examination was 53.8 years+/-7.2 (range 44-67 years). Disease onset was self-reported to be at age 18.4 years+/-3.8. First examination was at age 25.1 years+/-9.4 and the mean number of years between first and last examination was 28.7 years. Mean central corneal curvature was 6.87mm (48.77D)+/ 0.65 and 6.56mm (51.09D)+/-0.74, at first and last examination, respectively, a difference which was significant (p<0.001). However, the last measurement of corneal curvature was found to remain approximately constant over the years from about 20 to 50 years after onset. Mean BCVA was not significantly different between first and last examination and was found to be approximately constant over the years. CONCLUSION: Corneal curvature became steeper possibly within the first 20 years after disease onset but remained approximately unchanged afterwards. Likewise, BCVA remained practically constant over the years indicating relative stability of the disease after 20 years. PMID- 26142153 TI - Response of top shell assemblages to cyclogenesis disturbances. A case study in the Bay of Biscay. AB - Cyclones and other climate disturbances profoundly affect coastal ecosystems, promoting changes in the benthic communities that require time, sometimes even years, for a complete recovery. In this study we have analysed the morphological and genetic changes occurred in top shell (Gibbula umbilicalis and Phorcus lineatus) assemblages from the Bay of Biscay following explosive cyclogenesis events in 2014. Comparison with previous samples at short (three years before the cyclogenesis) and long (Upper Pleistocene) temporal scales served to better evaluate the extent of change induced by these disturbances in a more global dimension. A significant increase in mean size after the cyclogenesis was found for the two species, suggesting selective sweeping of small individuals weakly adhered to substrata. Loss of haplotype variants at the cytochrome oxidase subunit I gene suggests a population bottleneck, although it was not intense enough to produce significant changes in haplotype frequencies. The high population connectivity and metapopulation structuring of the two species in the area likely help the populations to recover from disturbances. At a wider temporal scale, cyclogenesis effects seemed to compensate the apparent decreasing trends in size for P. lineatus occurred after the Pleistocene-Holocene transition. Considering disturbance regimes for population baselines is recommended when the long-term effects of climate and anthropogenic pressures are evaluated. PMID- 26142154 TI - Hip abductor strength in people with knee osteoarthritis: A cross-sectional study of reliability and association with function. AB - BACKGROUND: To investigate the clinical importance of hip abductor (HA) strength in people with knee osteoarthritis (OA), the purposes of this study were to 1) compare the association of HA strength and physical function to that of knee extensor (KE) strength and physical function, and 2) determine the reliability of the assessment of HA strength using a hand-held dynamometer. METHODS: Thirty-five individuals [58 years standard deviation 10 years old] with knee osteoarthritis participated. Physical function was assessed with performance-based [Get-Up and Go (GUG), stair climb and descent (SC), and five times chair rise (CR)] and self reported (WOMAC function) measures. The relationship between strength and function was assessed using bivariate correlation and hierarchical multiple regression models. Reliability across sessions was assessed in 25 subjects. RESULTS: In the bivariate models, both KE and HA strength were both significantly associated with performance-based measures of function, but not WOMAC function. After controlling for anthropometric factors and KE strength in the hierarchical models, HA made significant independent contributions to the prediction of GUG and SC, but not CR or WOMAC function. The reliability of HA strength was excellent (ICC2, 3=0.94; 95% CI=0.86-0.97), while the minimum detectable change (MDC95) was 0.29Nm/kg (95% CI=0.23-0.41). CONCLUSION: HA strength can be reliably measured and is closely associated with functional performance in people with knee OA. CLINICAL RELEVANCE: These results provide preliminary evidence suggesting that HA strength may be an important rehabilitation target for the conservative management of knee OA. PMID- 26142155 TI - In vitro keratinocyte expansion for cell transplantation therapy is associated with differentiation and loss of basal layer derived progenitor population. AB - An alternative approach for traditional clinical mesh grafting in burn wound treatment is the use of expanded autologous keratinocytes in suspension or sheets that are cultured over 2-4 weeks in a remote service facility. While a wound reepithelialization has been described, the functional and aesthetic outcome is under debate. Cell isolation from split-skin donor tissue aims to preserve the valuable stem cell progenitors from the basal epidermal layer and to provide patients with a rapid wound reepithelialization and a satisfying outcome. While the presence of epidermal progenitors in the cell graft is thought to enable an improved epidermal surface post reepithelialization, we investigated a feasible clinical approach involving cultured versus noncultured epidermal cells comparing the alpha6int(high)/K15(high)/FSC(low)/SSC(low) and alpha6int(high)/K5(high)/FSC(low)/SSC(low) keratinocyte progenitor subpopulations before and after in vitro culture process. Our results show a significant increase of cell size during in vitro passaging and a decrease of progenitor markers linked to a gradual differentiation. A provision of the regenerative epidermal progenitors, isolated from the split-skin biopsy and applied directly onto the wound in an on-site setting of isolation and cell spray grafting in the operation room, could be of interest when choosing options for skin wound care with autologous cells. PMID- 26142156 TI - Development of quantitative structure activity relationship (QSAR) model for disinfection byproduct (DBP) research: A review of methods and resources. AB - Quantitative structure-activity relationship (QSAR) models are tools for linking chemical activities with molecular structures and compositions. Due to the concern about the proliferating number of disinfection byproducts (DBPs) in water and the associated financial and technical burden, researchers have recently begun to develop QSAR models to investigate the toxicity, formation, property, and removal of DBPs. However, there are no standard procedures or best practices regarding how to develop QSAR models, which potentially limit their wide acceptance. In order to facilitate more frequent use of QSAR models in future DBP research, this article reviews the processes required for QSAR model development, summarizes recent trends in QSAR-DBP studies, and shares some important resources for QSAR development (e.g., free databases and QSAR programs). The paper follows the four steps of QSAR model development, i.e., data collection, descriptor filtration, algorithm selection, and model validation; and finishes by highlighting several research needs. Because QSAR models may have an important role in progressing our understanding of DBP issues, it is hoped that this paper will encourage their future use for this application. PMID- 26142157 TI - Elevation of arginine decarboxylase-dependent putrescine production enhances aluminum tolerance by decreasing aluminum retention in root cell walls of wheat. AB - Aluminum (Al) stress induces putrescine (Put) accumulation in several plants and this response is proposed to alleviate Al toxicity. However, the mechanisms underlying this alleviation remain largely unknown. Here, we show that exposure to Al clearly increases Put accumulation in the roots of wheat plants (Triticum aestivum L. 'Xi Aimai-1') and that this was accompanied by significant increase in the activity of arginine decarboxylase (ADC), a Put producing enzyme. Application of an ADC inhibitor (d-arginine) terminated the Al-induced Put accumulation, indicating that increased ADC activity may be responsible for the increase in Put accumulation in response to Al. The d-arginine treatment also increased the Al-induced accumulation of cell wall polysaccharides and the degree of pectin demethylation in wheat roots. Thus, it elevated Al retention in cell walls and exacerbated Al accumulation in roots, both of which aggravate Al toxicity in wheat plants. The opposite effects were true for exogenous Put application. These results suggest that ADC-dependent Put accumulation plays important roles in providing protection against Al toxicity in wheat plants through decreasing cell wall polysaccharides and increasing the degree of pectin methylation, thus decreasing Al retention in the cell walls. PMID- 26142158 TI - Risk-based design of process plants with regard to domino effects and land use planning. AB - Land use planning (LUP) as an effective and crucial safety measure has widely been employed by safety experts and decision makers to mitigate off-site risks posed by major accidents. Accordingly, the concept of LUP in chemical plants has traditionally been considered from two perspectives: (i) land developments around existing chemical plants considering potential off-site risks posed by major accidents and (ii) development of existing chemical plants considering nearby land developments and the level of additional off-site risks the land developments would be exposed to. However, the attempts made to design chemical plants with regard to LUP requirements have been few, most of which have neglected the role of domino effects in risk analysis of major accidents. To overcome the limitations of previous work, first, we developed a Bayesian network methodology to calculate both on-site and off-site risks of major accidents while taking domino effects into account. Second, we combined the results of risk analysis with Analytic Hierarchical Process to design an optimal layout for which the levels of on-site and off-site risks would be minimum. PMID- 26142159 TI - Antimicrobial electrospun silver-, copper- and zinc-doped polyvinylpyrrolidone nanofibers. AB - The use of electrospun polyvinylpyrrolidone (PVP) nanofibers containing silver, copper, and zinc nanoparticles was studied to prepare antimicrobial mats using silver and copper nitrates and zinc acetate as precursors. Silver became reduced during electrospinning and formed nanoparticles of several tens of nanometers. Silver nanoparticles and the insoluble forms of copper and zinc were dispersed using low molecular weight PVP as capping agent. High molecular weight PVP formed uniform fibers with a narrow distribution of diameters around 500 nm. The fibers were converted into an insoluble network using ultraviolet irradiation crosslinking. The efficiency of metal-loaded mats against the bacteria Escherichia coli and Staphylococcus aureus was tested for different metal loadings by measuring the inhibition of colony forming units and the staining with fluorescent probes for metabolic viability and compromised membranes. The assays included the culture in contact with mats and the direct staining of surface attached microorganisms. The results indicated a strong inhibition for silver-loaded fibers and the absence of significant amounts of viable but non culturable microorganisms. Copper and zinc-loaded mats also decreased the metabolic activity and cell viability, although in a lesser extent. Metal-loaded fibers allowed the slow release of the soluble forms of the three metals. PMID- 26142160 TI - Health Care Transition Experiences of Young Adults With Cerebral Palsy. AB - Health care transition (HCT) describes the purposeful, planned movement of adolescents from child to adult-orientated care. The purpose of this qualitative study is to uncover the meaning of transition to adult-centered care as experienced by young adults with cerebral palsy (YA-CP) through the research question: What are the lived experiences of young adults with cerebral palsy transitioning from pediatric to adult healthcare? Six females and 3 males, aged 19-25 years of age, who identified as carrying the diagnosis of cerebral palsy without cognitive impairment, were interviewed. Giorgi's (1985) method for analysis of phenomenology was the framework for the study and guided the phenomenological reduction. The meaning of the lived experiences of YA-CPs transition to adult health care is expert novices with evidence and experience based expectations, negotiating new systems interdependently and accepting less than was expected. More information and support is needed for the YA-CP during transition to ensure a well-organized move to appropriate adult-oriented health care that is considerate of the lifelong impact of the disorder. The nurses' role as advocate, mentor and guide can optimize the individual's response to the transition process. PMID- 26142161 TI - An enigma: why vitamin A supplementation does not always reduce mortality even though vitamin A deficiency is associated with increased mortality. AB - BACKGROUND: Vitamin A deficiency (VAD) is associated with increased mortality. To prevent VAD, WHO recommends high-dose vitamin A supplementation (VAS) every 4-6 months for children aged between 6 months and 5 years of age in countries at risk of VAD. The policy is based on randomized clinical trials (RCTs) conducted in the late 1980s and early 1990s. Recent RCTs indicate that the policy may have ceased to be beneficial. In addition, RCTs attempting to extend the benefits to younger children have yielded conflicting results. Stratified analyses suggest that whereas some subgroups benefit more than expected from VAS, other subgroups may experience negative effects. METHODS AND RESULTS: We reviewed the potential modifiers of the effect of VAS. The variable effect of VAS was not explained by underlying differences in VAD. Rather, the effect may depend on the sex of the child, the vaccine status and previous supplementation with vitamin A. Vitamin A is known to affect the Th1/Th2 balance and, in addition, recent evidence suggests that vitamin A may also induce epigenetic changes leading to down-regulation of the innate immune response. Thus VAS protects against VAD but has also important and long-lasting immunological effects, and the effect of providing VAS may vary depending on the state of the immune system. CONCLUSIONS: To design optimal VAS programmes which target those who benefit and avoid those harmed, more studies are needed. Work is ongoing to define whether neonatal VAS should be considered in subgroups. In the most recent RCT in older children, VAS doubled the mortality for males but halved mortality for females. Hence, we urgently need to re-assess the effect of VAS on older children in large-scale RCTs powered to study effect modification by sex and other potential effect modifiers, and with nested immunological studies. PMID- 26142162 TI - Information and Communication Technology Use Among Low-Income Pregnant and Postpartum Women by Race and Ethnicity: A Cross-Sectional Study. AB - BACKGROUND: Pregnancy and the postpartum period provide windows of opportunity to impact perinatal and lifelong preventive health behavior for women and their families, but these opportunities are often missed. Understanding racial/ethnic differences in information and communication technology (ICT) use could inform technology-based interventions in diverse populations. OBJECTIVE: The objective of the study was to evaluate differences in the use of ICT between racial and ethnic groups as well as by English language proficiency. METHODS: We conducted a cross-sectional study of 246 women who were aged 18 years or older and pregnant or within 1 year of delivery. They were recruited from 4 hospital-based outpatient clinics and completed a self-administered survey. We used multivariate regression analysis to evaluate the association between race/ethnicity and ICT (mobile phone/short message service [SMS] text message, Internet, and social network) usage by race/ethnicity and perceived English language proficiency after adjusting for age, income, marital status, and insurance status. RESULTS: In all, 28% (69/246) of participants were Latina, 40% (98/246) were African American, 23% (56/246) were white, and 9% (23/246) from other racial/ethnic groups. Of the Latinas, 84% (58/69) reported limited English language proficiency and 59% (41/69) were uninsured. More than 90% of all participants reported mobile phone use, but more than 25% (65/246) had changed phone numbers 2 or more times in the past year. Compared to white women, African American women were less likely to SMS text message (OR 0.07, 95% CI 0.01-0.63) and Latinas were less likely to use the Internet to find others with similar concerns (OR 0.23, 95% CI 0.08-0.73). Women with limited English language proficiency were less likely to use the Internet overall (OR 0.30, 95% CI 0.09-0.99) or use email (OR 0.22, 95% CI 0.08 0.63) compared to women with adequate English language proficiency. CONCLUSIONS: Mobile phones are widely available for the delivery of health interventions to low-income, racially diverse pregnant and postpartum women, but disparities in Internet use and SMS text messaging exist. Interventions or programs requiring Web-based apps may have lower uptake unless alternatives are available, such as those adapted for limited English proficiency populations. PMID- 26142163 TI - Pathological gambling associated with CADASIL: an unusual manifestation. PMID- 26142164 TI - Radiographic positions of femoral ACL, AM and PL centres: accuracy of guidelines based on the lateral quadrant method. AB - PURPOSE: Femoral tunnel positioning is an important factor in anatomical ACL reconstructions. To improve accuracy, lateral radiographic support can be used to determine the correct tunnel location, applying the quadrant method. Piefer et al. (Arthroscopy 28:872-881, 2012) combined various outcomes of eight studies applying this method to one guideline. The studies included in that guideline used various insertion margins, imaging techniques and measurement methods to determine the position of the ACL centres. The question we addressed is whether condensing data from various methods into one guideline, results in a more accurate guideline than the results of one study. METHODS: The accuracy of the Piefer's guideline was determined and compared to a guideline developed by Luites et al. (2000). For both guidelines, we quantified the mean absolute differences in positions of the actual anatomical centres of the ACL, AM and PL measured on the lateral radiographs of twelve femora with the quadrant method and the positions according to the guidelines. RESULTS: The accuracy of Piefer's guidelines was 2.4 mm (ACL), 2.7 mm (AM) and 4.6 mm (PL), resulting in positions significantly different from the actual anatomical centres. Applying Luites' guidelines for ACL and PL resulted in positions not significantly different from the actual centres. The accuracies were 1.6 mm (ACL) and 2.2 mm (PL and AM), which were significantly different from Piefer for the PL centres, and therefore more accurate. CONCLUSIONS: Condensing the outcomes of multiple studies using various insertion margins, imaging techniques and measurement methods, results in inaccurate guidelines for femoral ACL tunnel positioning at the lateral view. CLINICAL RELEVANCE: An accurate femoral tunnel positioning for anatomical ACL reconstruction is a key issue. The results of this study demonstrate that averaging of various radiographic guidelines for anatomical femoral ACL tunnel placement in daily practice, can result in inaccurate tunnel positions. LEVEL OF EVIDENCE: Diagnostic study, Level 1. PMID- 26142165 TI - No condylar lift-off occurs because of excessive lateral soft tissue laxity in neutrally aligned total knee arthroplasty: a computer simulation study. AB - PURPOSE: Condylar lift-off can induce excessive polyethylene wear after total knee arthroplasty (TKA). A computer simulation was used to evaluate the influence of femoral varus alignment and lateral collateral ligament (LCL) laxity on lift off after single-design TKA. It was hypothesised that proper ligament balancing and coronal alignment would prevent lift-off. METHODS: The computer model in this study is a dynamic musculoskeletal program that simulates gait up to 60 degrees of knee flexion. The lift-off phenomenon was defined as positive with an intercomponent distance of >2 mm. In neutrally aligned components in the coronal plane, the femoral and tibial components were set perpendicular to the femoral and tibial mechanical axis, respectively. The femoral coronal alignment was changed from neutral to 5 degrees varus in 1 degrees increments. Simultaneously, the LCL length was elongated from 0 to 5 mm in 1-mm increments to provide a model of pathological slack. RESULTS: Within 2 degrees of femoral varus alignment, lift-off did not occur even if the LCL was elongated by up to 5 mm. However, lift-off occurred easily in the stance phase in femoral varus alignments of >3 degrees with slight LCL slack. The contact forces of the tibiofemoral joint were influenced more by femoral varus alignment than by LCL laxity. CONCLUSIONS: Aiming for neutral alignment in severely varus knees makes it difficult to achieve appropriate ligament balance. Our study suggests that no lift-off occurs with excessive LCL laxity alone in a neutrally aligned TKA and therefore that varus alignment should be avoided to decrease lift-off after TKA. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 26142166 TI - A real-world perspective on the prevalence and treatment of heart failure with a reduced ejection fraction but no specific or only mild symptoms. AB - Heart failure (HF) is commonly described according to the severity of symptoms, using the New York Heart Association (NYHA) classification, and the assessment of ventricular function, by measuring the left ventricular ejection fraction (LVEF). It is important to acknowledge, however, that the severity of symptoms does not systematically correlate with the level of ventricular systolic dysfunction. Patients with no or only mild symptoms are still at high risk of HF-related morbidity and mortality. The objective of this review was to summarize the prevalence, characteristics, and treatment of patients with chronic HF and mild or no symptoms and to review epidemiological data from three recent registries conducted in Europe. From a clinical practice perspective, patients with a reduced ejection fraction who have only mild symptoms appear to represent a group of patients for whom the provision of adequate medical care is yet to be optimized. While prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers appears to be consistently high, the use of mineralocorticoid receptor antagonists is more variable and does not appear to be in accordance with the latest clinical guidelines. As approximately half of patients with HF and a reduced LVEF have NYHA class II symptoms, significant reductions in morbidity and mortality could be achieved by more comprehensive treatment of this population. PMID- 26142167 TI - Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti Tumor Necrosis Factor Therapy for Crohn's Disease: A Meta-analysis of Placebo controlled Trials. AB - BACKGROUND & AIMS: There is debate over whether patients with Crohn's disease who start anti-tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy. METHODS: We performed a systematic review of literature published from 1980 through 2008 and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn's disease. We excluded RCTs of patients who were naive to anti-TNF and immunomodulator therapy. The primary end points were clinical response at weeks 4-14 and 24-30 and remission at weeks 24 30. Secondary end points included infusion site or injection site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents. RESULTS: Overall, combination therapy was no more effective than monotherapy in inducing 6-month remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80-1.31), inducing a response (OR, 1.08; 95% CI, 0.79-1.48), maintaining a response (OR, 1.53; 95% CI, 0.67-3.49), or inducing partial (OR, 1.25; 95% CI, 0.84-1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68 1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97-3.07), adalimumab (OR, 0.88; 95% CI, 0.58-1.35), or certolizumab (OR, 0.93; 95% CI, 0.65-1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26-0.79.) CONCLUSIONS: On the basis of a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated. PMID- 26142168 TI - Efficacy of combined physical and occupational therapy in patients with conservatively treated distal radius fracture: randomized controlled trial. AB - AIM: To evaluate the efficacy of combined physical and occupational therapy in comparison with physical therapy alone in patients with conservatively treated distal radius fracture. METHODS: Sixty-one participants, conservatively treated after a distal radius fracture, were included in a randomized and single-blind trial. Group A had physical therapy only (n = 31) and group B had physical and occupational therapy (n = 30). The assessment was performed three times: upon inclusion in the study in the first week after removal of the cast (T1), immediately after the end of the rehabilitation (T2), and 1 month after completing the rehabilitation (T3). The passive wrist range-of-motion, grip strength, and Disabilities of Arm, Shoulder and Hand (DASH) score were used as rehabilitation outcomes. RESULTS: Rehabilitation outcomes were analyzed using two way mixed analysis of variance. The effect of time was statistically significant (p < 0.001) for all outcomes. The group (therapy) factor was statistically significant for grip strength only (p = 0.038). The interaction effect was statistically significant for rotation (p = 0.034) and grip strength (p = 0.021). A comparison between time points T3:T1 showed statistically significant difference in grip strength in favor of group B 67 % (95 % CI 60-74 %) versus group A 53 % (95 % CI 45-61 %), p = 0.024. CONCLUSION: The combined therapy resulted in a statistically significant increase of grip strength in comparison with isolated physical therapy in the period of 12-16 weeks after the fracture. This effectiveness was not confirmed with DASH score results. PMID- 26142169 TI - A long-term evaluation of cryoballoon ablation in 205 atrial fibrillation patients: a single center experience. AB - BACKGROUND: Atrial fibrillation is the most prevalent cardiac arrhythmia with significant healthcare impact with regards to treatment costs, morbidity, and mortality. Many of the focal electrical activities that initiate and sustain atrial fibrillation have been found to reside within or near the pulmonary veins. Consequently, pulmonary vein isolation by catheter ablation has emerged as an effective method to eliminate the focal triggers associated with atrial fibrillation. METHODS: In this single-center study, 205 patients were ablated for atrial fibrillation using a cryoballoon catheter and followed-up long-term by retrospective chart examination to evaluate their post-procedural freedom from atrial fibrillation. RESULTS: Patients were followed for up to 6 years with a cohort median of 3 years of post-ablation evaluation. Overall, at 12, 24, and 36 months post-ablation, 71, 49, and 31% of evaluated patients were free of atrial fibrillation, respectively. We found the type of atrial fibrillation (paroxysmal vs. persistent) as an independent predictor for arrhythmia recurrence (HR 1.97; 95% CI: 1.24-3.13, P = 0.006). The cohort median atrial fibrillation-free survival time was 24 months (27 months for paroxysmal atrial fibrillation patients and 14 months for persistent atrial fibrillation patients). There were a total of 37 (18%) complications, 8 (3.9%) were categorized as major complications, all without permanent sequels. The most common complication was phrenic nerve palsy which occurred in 14 (6.8%) patients. CONCLUSION: Long-term outcomes in this study suggest that the pulmonary vein isolation using the cryoballoon technique is relatively an effective method especially in the treatment of paroxysmal atrial fibrillation. PMID- 26142170 TI - Inpatient smoking cessation therapy: truth or dare? AB - BACKGROUND: This study aims to answer the question to which extent even very heavy nicotine-dependent smokers can benefit from a 3-week inpatient smoking cessation program. A particular focus lies on analyzing the positive effects, which go above and beyond normally anticipated health benefits. METHODS: This is a descriptive study observing 270 patients over a 1-year period consisting of recruitment, therapy, and two post-therapy follow-up visits at 6-month interval. Gender differences, changes in body weight, and factors relating to addiction and the nicotine withdrawal process are analyzed. In comparing successful participants-post-therapy nonsmokers-with less successful ones, our analysis identifies benefits and advantages an inpatient smoking cessation therapy can bring to even the heaviest smokers. RESULTS: At the 12-month post-therapy follow up visit, 42.6% of participants were identified as nonsmokers. A total of 34.0% of participants took up smoking again. No data is available on the remaining participants. Nonsmokers experienced significant reduction in nicotine craving and withdrawal symptoms. In terms of body weight, increases were found in both, men and women, nonsmokers and smokers. CONCLUSION: Successful quitters fail to report of an unbearable strong desire to smoke. Such unfounded fear should be communicated. Weight gain remains an undesired side effect. Hence, it is crucial to diagnose individuals more prone to weight gain and offer coping strategies thus reducing the risk of developing obesity. Nevertheless, the outcome of the study should be an encouragement to also heavy smokers and empower them to undertake smoking cessation. PMID- 26142171 TI - The evaluation in terms of sarcopenia of patients with fibromyalgia syndrome. AB - BACKGROUND: Fibromyalgia syndrome (FMS) is an extra-articular rheumatic illness, characterized by widespread body pain and decreased muscle function. Generalized loss of muscle mass and strength is named as sarcopenia. The objective of this study was to evaluate patients with FMS regarding sarcopenia. METHODS: This was a cross sectional, case-controlled, single-blinded, and single-centered study. The FMS patients were assessed by Fibromyalgia Impact Questionnaire (FIQ), visual analog scale (VAS), Beck Depression Index (BDI), and Pittsburg Sleep Quality Scale (PSQI). All the participants were evaluated for sarcopenia by bioimpedance analysis (BIA), anthropometric measurements, handgrip strength, and the parameters of walking speed. RESULTS: In this study, 82 patients with FMS and 38 healthy control female subjects were included. VAS, BDI, and PSQI scores were statistically higher in the FMS group than the control group (p < 0.001). Handgrip strength (HS) and walking speed (WS) scores in the group with FMS were statistically lower than the control group (p = 0.023, p < 0.001 respectively). VAS score of FMS patients was significantly correlated with BIA, body mass index, waist circumference, HS, and WS scores (r = 0.284, p = 0.012; r = 0.228, p = 0.045; r = 0.249, p = 0.028; r = - 0.361, p = 0.001; and r = - 0.230, p = 0.043 respectively). Also FIQ in patients was significantly correlated with BIA, waist circumference, HS, WS, and body mass index (r = 0.267, p = 0.018; r = 0.291, p = 0.010; r = - 0.319, p = 0.004; r = - 0.360, p = 0.001; and r = 0.304, p = 0.007 respectively). CONCLUSION: Evaluation of female patients with primary FMS by the sarcopenia parameters could contribute a more objective evaluation during the patients' follow-up. PMID- 26142172 TI - Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review. AB - Mixed connective tissue disease (MCTD) is a rare connective tissue disease frequently involving the lungs. The main characteristic is a systemic sclerosis like picture of slowly progressing interstitial lung disease consistent with lung fibrosis, while pulmonary arterial hypertension is rare. Herein, we present a case of a newly diagnosed MCTD patient developing life-threatening acute pneumonitis similar to lupus pneumonitis. Previous literature on this exceptionally rare complication of MCTD is reviewed and differential diagnosis and management discussed. PMID- 26142173 TI - Molecular structure, FT-IR, FT-Raman, NBO, HOMO and LUMO, MEP, NLO and molecular docking study of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid. AB - The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of the normal modes of vibrations was done using GAR2PED program. (1)H NMR chemical shifts calculations were carried out by using B3LYP functional with SDD basis set. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. MEP was performed by the DFT method and the predicted infrared intensities and Raman activities have also been reported. The calculated geometrical parameters are in agreement with that of similar derivatives. The title compound forms a stable complex with PknB as is evident from the binding affinity values and the molecular docking results suggest that the compound might exhibit inhibitory activity against PknB and this may result in development of new anti-tuberculostic agents. PMID- 26142174 TI - FT-IR, HOMO-LUMO, NBO, MEP analysis and molecular docking study of 3-Methyl-4 {(E)-[4-(methylsulfanyl)-benzylidene]amino}1H-1,2,4-triazole-5(4H)-thione. AB - FT-IR spectrum of 3-Methyl-4-{(E)-[4-(methylsulfanyl)-benzylidene]amino}1H-1,2,4 triazole-5(4H)-thione was recorded and analysed. The vibrational wavenumbers were computed and at HF and DFT levels of theory. The data obtained from wavenumber calculations are used to assign the vibrational bands obtained in the IR spectrum. The NH stretching wavenumber is red shifted in the IR spectrum from the computed value, which indicates the weakening of the NH bond. The geometrical parameters of the title compound are in agreement with the XRD results. NBO analysis, HOMO-LUMO, first and second order hyperpolarizability and molecular electrostatic potential results are also reported. From the MEP map it is evident that the negative regions are localized over the sulphur atoms and N3 atom of triazole ring and the maximum positive region is localized on NH group, indicating a possible site for nucleophilic attack. Prediction of Activity Spectra analysis of the title compound predicts anti-tuberculostic activity with probability to be active value of 0.543. Molecular docking studies reveal that the triazole nitrogen atoms and the thione sulphur atom play vital role in bonding and results draw us to the conclusion that the compound might exhibit anti-tuberculostic activity. PMID- 26142175 TI - Dielectric and FT-Raman spectroscopic approach to molecular identification of breast tumor tissues. AB - FT-Raman spectra and dielectric properties of benign and malignant women breast tissues in vitro were investigated. FT-Raman spectra for the malignant tissues showed a remarkably decrease in the lipid/protein ratio. Dielectric properties of women breast tissues measured in the low frequency range (42-10(6)Hz) were interpreted in spite of electrode polarization effect. Experimental results showed a contrast between the dielectric properties of malignant (Grade II) and benign tissues within the frequency range studied. The permittivity of malignant to normal breast tissue was found to be 160:1 while it could be 1.3:1 for fibrocystic breast tissues. These findings could contribute to distinguish between two breast tissues. The differences in spectral features between benign and malignant tissues may lead to breast cancer detection. PMID- 26142176 TI - pH controlled Ho3+-Yb3+ codoped Y2O3 nanowires for display devices. AB - The wire like structure with particle size in the nanometer range of Ho(3+) Yb(3+) codoped Y2O3 phosphors have been synthesized through hydrothermal synthesis route by controlling the pH value. The Field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD) analysis of the synthesized phosphor powders have been studied which confirms the formation of nanowires in the prepared materials and the formation of proper crystalline structure respectively. The frequency upconversion emission spectra under 980 nm excitation have been recorded and an efficient green emission has been observed. The excitation energy corresponding to the NIR photon seems to be fully utilized for the emission lying in the green region. The Fourier transform infrared (FTIR) spectroscopic analysis for existence of the impurities in the developed material has also been performed. The experimental observation proves the utility of the prepared material in the display devices and diagnosis purposes. PMID- 26142177 TI - A water-soluble pH fluorescence probe based on quaternary ammonium salt for bioanalytical applications. AB - A novel fluorescence probe Rhodamine-Ethanediamine-Iodomethane (REI) was successfully prepared to serve as an efficient sensing platform for H(+) with fully reversibility mainly between the pH 4.2 and 7.2 in simple buffer solution. The introduction of quaternary ammonium salt with positive charge can not only manage to increase the solubility and sensitivity of probe REI, but also avoid the "alkalizing effect" due to charge-induced effect compared to the reference probe Rhodamine-Ethanediamine (RE). In particular, probe REI was well used for monitoring the weak acid pH fluctuations in lysosome of the live HeLa cells due to its excellent biological properties, including low cytotoxicity, high selectivity, good sensitivity and membrane permeability. PMID- 26142178 TI - The role of corticosteroids in acute-severe autoimmune hepatitis is still highly debatable. PMID- 26142179 TI - Randomized study of danoprevir/ritonavir-based therapy for HCV genotype 1 patients with prior partial or null responses to peginterferon/ribavirin. PMID- 26142181 TI - Atherosclerosis. Preface. PMID- 26142180 TI - Galectin-3 and HBME-1 improve the accuracy of core biopsy in indeterminate thyroid nodules. AB - Core needle biopsy (CNB) has been recently described as an accurate second-line test in thyroid inconclusive cytology (FNA). Here we retrospectively investigated the potential improvement given by Galectin-3, Cytokeratin-19, and HBME-1 on the accuracy of CNB in thyroid nodules with prior indeterminate FNA report. The study included 74 nodules. At CNB diagnosis, 15 were cancers, 40 were benign, and 19 had uncertain/non-diagnostic CNB report. The above immunohistochemical (IHC) panel was analyzed in all cases. After surgery, 19 malignant and 55 benign lesions were found. All 15 cancers and all 40 benign nodules diagnosed at CNB were confirmed at final histology. Regarding the uncertain CNB group, 4 (21 %) were malignant and 15 (79 %) benign. When we considered all the series, the most accurate IHC combination was Galectin-3 plus HBME-1, while HBME-1 was the most sensitive marker in those nodules with uncertain CNB report. The combination of CNB plus IHC could indentify 19/19 cancers and 53/55 benign lesions. Sensitivity and specificity of CNB increased from 79 to 100 % and from 73 to 96 %, respectively, by adding IHC. CNB can diagnose the majority of thyroid nodules with previous indeterminate FNA cytology, while the accuracy of CNB is increased by adding Galectin-3, Cytokeratin-19, and HBME-1 panel. We suggest to adopt CNB as a second-line approach to indeterminate thyroid FNA, and apply IHC in those lesions with uncertain/non-diagnostic CNB report. This approach should improve the pre-surgical diagnosis of patients. These results should be confirmed in larger prospective series. PMID- 26142182 TI - The "serendipitous brain": Low expectancy and timing uncertainty of conscious events improve awareness of unconscious ones (evidence from the Attentional Blink). AB - To anticipate upcoming sensory events, the brain picks-up and exploits statistical regularities in the sensory environment. However, it is untested whether cumulated predictive knowledge about consciously seen stimuli improves the access to awareness of stimuli that usually go unseen. To explore this issue, we exploited the Attentional Blink (AB) effect, where conscious processing of a first visual target (T1) hinders detection of early following targets (T2). We report that timing uncertainty and low expectancy about the occurrence of consciously seen T2s presented outside the AB period, improve detection of early and otherwise often unseen T2s presented inside the AB. Recording of high resolution Event Related Potentials (ERPs) and the study of their intracranial sources showed that the brain achieves this improvement by initially amplifying and extending the pre-conscious storage of T2s' traces signalled by the N2 wave originating in the extra-striate cortex. This enhancement in the N2 wave is followed by specific changes in the latency and amplitude of later components in the P3 wave (P3a and P3b), signalling access of the sensory trace to the network of parietal and frontal areas modulating conscious processing. These findings show that the interaction between conscious and unconscious processing changes adaptively as a function of the probabilistic properties of the sensory environment and that the combination of an active attentional state with loose probabilistic and temporal expectancies on forthcoming conscious events favors the emergence to awareness of otherwise unnoticed visual events. This likely provides an insight on the attentional conditions that predispose an active observer to unexpected "serendipitous" findings. PMID- 26142183 TI - Predicting prolonged length of hospital stay in older emergency department users: use of a novel analysis method, the Artificial Neural Network. AB - OBJECTIVE: To examine performance criteria (i.e., sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], likelihood ratios [LR], area under receiver operating characteristic curve [AUROC]) of a 10 item brief geriatric assessment (BGA) for the prediction of prolonged length hospital stay (LHS) in older patients hospitalized in acute care wards after an emergency department (ED) visit, using artificial neural networks (ANNs); and to describe the contribution of each BGA item to the predictive accuracy using the AUROC value. METHODS: A total of 993 geriatric ED users admitted to acute care wards were included in this prospective cohort study. Age >85years, gender male, polypharmacy, non use of formal and/or informal home-help services, history of falls, temporal disorientation, place of living, reasons and nature for ED admission, and use of psychoactive drugs composed the 10 items of BGA and were recorded at the ED admission. The prolonged LHS was defined as the top third of LHS. The ANNs were conducted using two feeds forward (multilayer perceptron [MLP] and modified MLP). RESULTS: The best performance was reported with the modified MLP involving the 10 items (sensitivity=62.7%; specificity=96.6%; PPV=87.1; NPV=87.5; positive LR=18.2; AUC=90.5). In this model, presence of chronic conditions had the highest contributions (51.3%) in AUROC value. CONCLUSIONS: The 10-item BGA appears to accurately predict prolonged LHS, using the ANN MLP method, showing the best criteria performance ever reported until now. Presence of chronic conditions was the main contributor for the predictive accuracy. PMID- 26142184 TI - Nsite, NsiteH and NsiteM computer tools for studying transcription regulatory elements. AB - Gene transcription is mostly conducted through interactions of various transcription factors and their binding sites on DNA (regulatory elements, REs). Today, we are still far from understanding the real regulatory content of promoter regions. Computer methods for identification of REs remain a widely used tool for studying and understanding transcriptional regulation mechanisms. The Nsite, NsiteH and NsiteM programs perform searches for statistically significant (non-random) motifs of known human, animal and plant one-box and composite REs in a single genomic sequence, in a pair of aligned homologous sequences and in a set of functionally related sequences, respectively. AVAILABILITY AND IMPLEMENTATION: Pre-compiled executables built under commonly used operating systems are available for download by visiting http://www.molquest.kaust.edu.sa and http://www.softberry.com. CONTACT: solovictor@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26142185 TI - JASSA: a comprehensive tool for prediction of SUMOylation sites and SIMs. AB - MOTIVATION: Post-translational modification by the Small Ubiquitin-like Modifier (SUMO) proteins, a process termed SUMOylation, is involved in many fundamental cellular processes. SUMO proteins are conjugated to a protein substrate, creating an interface for the recruitment of cofactors harboring SUMO-interacting motifs (SIMs). Mapping both SUMO-conjugation sites and SIMs is required to study the functional consequence of SUMOylation. To define the best candidate sites for experimental validation we designed JASSA, a Joint Analyzer of SUMOylation site and SIMs. RESULTS: JASSA is a predictor that uses a scoring system based on a Position Frequency Matrix derived from the alignment of experimental SUMOylation sites or SIMs. Compared with existing web-tools, JASSA displays on par or better performances. Novel features were implemented towards a better evaluation of the prediction, including identification of database hits matching the query sequence and representation of candidate sites within the secondary structural elements and/or the 3D fold of the protein of interest, retrievable from deposited PDB files. AVAILABILITY AND IMPLEMENTATION: JASSA is freely accessible at http://www.jassa.fr/. Website is implemented in PHP and MySQL, with all major browsers supported. CONTACT: guillaume.beauclair@inserm.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26142186 TI - al3c: high-performance software for parameter inference using Approximate Bayesian Computation. AB - MOTIVATION: The development of Approximate Bayesian Computation (ABC) algorithms for parameter inference which are both computationally efficient and scalable in parallel computing environments is an important area of research. Monte Carlo rejection sampling, a fundamental component of ABC algorithms, is trivial to distribute over multiple processors but is inherently inefficient. While development of algorithms such as ABC Sequential Monte Carlo (ABC-SMC) help address the inherent inefficiencies of rejection sampling, such approaches are not as easily scaled on multiple processors. As a result, current Bayesian inference software offerings that use ABC-SMC lack the ability to scale in parallel computing environments. RESULTS: We present al3c, a C++ framework for implementing ABC-SMC in parallel. By requiring only that users define essential functions such as the simulation model and prior distribution function, al3c abstracts the user from both the complexities of parallel programming and the details of the ABC-SMC algorithm. By using the al3c framework, the user is able to scale the ABC-SMC algorithm in parallel computing environments for his or her specific application, with minimal programming overhead. AVAILABILITY AND IMPLEMENTATION: al3c is offered as a static binary for Linux and OS-X computing environments. The user completes an XML configuration file and C++ plug-in template for the specific application, which are used by al3c to obtain the desired results. Users can download the static binaries, source code, reference documentation and examples (including those in this article) by visiting https://github.com/ahstram/al3c. CONTACT: astram@usc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26142187 TI - PSIKO2: a fast and versatile tool to infer population stratification on various levels in GWAS. AB - Genome-wide association studies are an invaluable tool for identifying genotypic loci linked with agriculturally important traits or certain diseases. The signal on which such studies rely upon can, however, be obscured by population stratification making it necessary to account for it in some way. Population stratification is dependent on when admixture happened and thus can occur at various levels. To aid in its inference at the genome level, we recently introduced psiko, and comparison with leading methods indicates that it has attractive properties. However, until now, it could not be used for local ancestry inference which is preferable in cases of recent admixture as the genome level tends to be too coarse to properly account for processes acting on small segments of a genome. To also bring the powerful ideas underpinning psiko to bear in such studies, we extended it to psiko2, which we introduce here. AVAILABILITY AND IMPLEMENTATION: Source code, binaries and user manual are freely available at https://www.uea.ac.uk/computing/psiko. CONTACT: Andrei-Alin.Popescu@uea.ac.uk or Katharina.Huber@cmp.uea.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26142188 TI - Data2Dynamics: a modeling environment tailored to parameter estimation in dynamical systems. AB - Modeling of dynamical systems using ordinary differential equations is a popular approach in the field of systems biology. Two of the most critical steps in this approach are to construct dynamical models of biochemical reaction networks for large datasets and complex experimental conditions and to perform efficient and reliable parameter estimation for model fitting. We present a modeling environment for MATLAB that pioneers these challenges. The numerically expensive parts of the calculations such as the solving of the differential equations and of the associated sensitivity system are parallelized and automatically compiled into efficient C code. A variety of parameter estimation algorithms as well as frequentist and Bayesian methods for uncertainty analysis have been implemented and used on a range of applications that lead to publications. AVAILABILITY AND IMPLEMENTATION: The Data2Dynamics modeling environment is MATLAB based, open source and freely available at http://www.data2dynamics.org. CONTACT: andreas.raue@fdm.uni-freiburg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26142189 TI - Changing urban phosphorus metabolism: Evidence from Longyan City, China. AB - Rapid worldwide urbanization calls for a better understanding of phosphorus (P) metabolism and the interaction of the physical, ecological and social drivers of P cycling in urban systems. We quantified the P metabolism in Longyan, a city with a major agricultural economy, and analyzed its long-term trends over the rapid urbanization period of 1985-2010. Both input P (from 4811 t P to 14,296 t P) and output P (from 4565 t P to 13,509 t P) increased significantly. The agricultural subsystem contributed most to the P metabolism, accounting for 85% of total P input. The share of P input lost to the environment, i.e. discharge to water, accumulation in the soil and landfill, increased from 66% to 72%, while food production efficiency decreased from 48% to 29%. Per capita P input showed linear relationships with the Human Development Index (HDI), S-curve relationship with the urbanization rate, and logistic curve relationship with per capita disposable income. A more meat-based diet shift both in Longyan and surrounding cities greatly affected Longyan's food production structure. Our results demonstrate that P metabolic quantity, configuration, and efficiency in production systems can change drastically in response to changes in consumer and producer behavior as well as in socioeconomic structure. A larger regional scale should be considered in urban P management, when trying to mitigate the increase in P use. The results also imply that sustainable urban P management will require a system-wide, cross-sector and cross-boundary approach. PMID- 26142191 TI - Flecainide-induced prolongation of ventricular repolarization contributes to the proarrhythmic profile of action. PMID- 26142190 TI - Bridging Multidimensional Models of Ethnic-Racial and Gender Identity Among Ethnically Diverse Emerging Adults. AB - The purpose of this study was to integrate and validate a multidimensional model of ethnic-racial identity and gender identity borrowing constructs and measures based on social identity and gender identity theories. Participants included 662 emerging adults (M age = 19.86 years; 75 % female) who self-identified either as Asian American, Latino/a, or White European American. We assessed the following facets separately for ethnic-racial identity and gender identity: centrality, in group affect, in-group ties, self-perceived typicality, and felt conformity pressure. Within each identity domain (gender or ethnicity/race), the five dimensions generally indicated small-to-moderate correlations with one another. Also, correlations between domains for each dimension (e.g., gender typicality and ethnic-racial typicality) were mostly moderate in magnitude. We also noted some group variations based on participants' ethnicity/race and gender in how strongly particular dimensions were associated with self-esteem. Finally, participants who scored positively on identity dimensions for both gender and ethnic-racial domains indicated higher self-esteem than those who scored high in only one domain or low in both domains. We recommend the application of multidimensional models to study social identities in multiple domains as they may relate to various outcomes during development. PMID- 26142192 TI - A novel quantitative assessment of whole blood thrombogenicity in patients treated with a non-vitamin K oral anticoagulant. PMID- 26142193 TI - Reduced CD31 expression on CD14(+)CD16(+) monocyte subset in acute coronary syndromes. PMID- 26142194 TI - The risk of tachyarrhythmias in patients with moderate-to-severe chronic kidney disease receiving tiotropium bromide. PMID- 26142195 TI - Accidentally crushed stent during complex bifurcation treatment. A potential cause of very late stent thrombosis. PMID- 26142196 TI - Antihypertensive drugs and statins should be considered in arterial stiffness evaluation in ethnic differences. PMID- 26142197 TI - Reply to letter by Kirat and Kose: Maximizing information from a 12-lead electrocardiogram. PMID- 26142198 TI - Risk stratification of normotensive pulmonary embolism based on the sPESI - Does it work for all patients? PMID- 26142199 TI - Acinetobacter baumannii and cardiac impairment. Increasingly important nosocomial pathogen. PMID- 26142200 TI - Association of atrial fibrillation and erectile dysfunction: Reply. PMID- 26142201 TI - Giant left atrium in a 9-year-old child. PMID- 26142202 TI - Dpp4 inhibition as a therapeutic strategy in cardiometabolic disease: Incretin dependent and -independent function. AB - Cardiometabolic disorders including obesity, diabetes and cardiovascular disease are among the most severe health problems worldwide. DPP4 enzymatic inhibitors were first developed as anti-diabetic reagents which preserve incretin hormones and promote post-prandial insulin secretion. It's been shown in animal studies that incretin-based therapy has a beneficial effect on cardiovascular disease. Recent studies demonstrated novel non-catalytic functions of DPP4 that may play a role in cardiometabolic disease. Although the role of DPP4 inhibition-mediated incretin effects has been well-reviewed, little information of its incretin independent actions was introduced in cardiometabolic disease. In the current review, we will summarize the catalytic dependent and independent effects of DPP4 inhibition on cardiometabolic disease. PMID- 26142203 TI - Autoantibodies against M2-muscarinic and beta adrenergic receptors: New mediators in atrial fibrillation? PMID- 26142204 TI - Role of vascular peroxidase 1 in senescence of endothelial cells in diabetes rats. AB - BACKGROUND: Reactive oxygen species (ROS) is thought as a major reason of vascular injury in diabetes. Vascular peroxidase 1 (VPO1) is a newly found peroxidase playing an important role in inducing oxidative stress. In the present experiment, we tested the role of VPO1 in senescence of endothelial cells in streptozotocin (STZ)-induced diabetic rats and cultured endothelial cells. METHODS: Blood samples were collected from carotid arteries. Vasodilator responses to acetylcholine (Ach) in the isolated aortic rings were measured, serum concentration of glucose, tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) and the expression of VPO1 in the aorta were determined. Endothelial cells were treated with high glucose or H2O2, the concentrations of MCP-1, TNF-alpha and hypochlorous acid (HOCl) and the expression of VPO1 were determined. shRNA of VPO1 was used for mechanism research in cultured cells. RESULTS: Vasodilator responses to Ach were impaired markedly and the serum concentrations of glucose, TNF-alpha and MCP-1 were significantly increased in diabetic rats. The expression of VPO1 in the aorta was upregulated in diabetic rats. High glucose treatment significantly decreased cell viability and elevated the levels of MCP-1, TNF-alpha and HOCl and upregulated the expression of VPO1. H2O2 treatment significantly induced cellular senescence, inhibited eNOS expression and NO production. The effects of high glucose and H2O2 were attenuated by shRNA interference of VPO1. CONCLUSIONS: VPO1 plays an important role in senescence of endothelial cells and endothelial dysfunction by induction of oxidative stress and inflammatory reaction in type 2 diabetic rats. PMID- 26142205 TI - Perturbations in fatty acid metabolism and apoptosis are manifested in calcific coronary artery disease: An exploratory lipidomic study. AB - BACKGROUND: Controversy exists concerning the beneficial or harmful effects of the presence of ectopic calcification in the coronary arteries. Additionally, further elucidation of the exact pathophysiological mechanism is needed. In this study, we sought to identify metabolic markers of vascular calcification that could assist in understanding the disease, monitoring its progress and generating hypotheses describing its pathophysiology. METHODS: Untargeted lipid profiling and complementary modeling strategies were employed to compare serum samples from patients with different levels of calcific coronary artery disease (CCAD) based on their calcium score (CS). Subsequently, patients were divided into three groups: no calcification (NC; CS=0; n=26), mild calcification (MC; CS:1-250; n=27) and severe (SC; CS>250; n=17). RESULTS: Phosphatidylcholine levels were found to be significantly altered in the disease states (p=0.001-0.04). Specifically, 18-carbon fatty acyl chain (FAC) phosphatidylcholines were detected in lower levels in the SC group, while 20:4 FAC lipid species were detected in higher concentrations. A statistical trend was observed with phosphatidylcholine lipids in the MC group, showing the same tendency as with the SC group. We also observed several sphingomyelin signals present at lower intensities in SC when compared with NC or MC groups (p=0.000001-0.01). CONCLUSIONS: This is the first lipid profiling study reported in CCAD. Our data demonstrate dysregulations of phosphatidylcholine lipid species, which suggest perturbations in fatty acid elongation/desaturation. The altered levels of the 18-carbon and 20:4 FAC lipids may be indicative of disturbed inflammation homeostasis. The marked sphingomyelin dysregulation in SC is consistent with profound apoptosis as a potential mechanism of CCAD. PMID- 26142206 TI - Endothelial progenitor cells: Cardiovascular protection in Parkinson's disease? PMID- 26142207 TI - Detrimental effects of cardiac resynchronization therapy on the non-responders. PMID- 26142208 TI - The prevalence and risk factors of cerebral microbleeds in patients with Parkinson's disease. AB - INTRODUCTION: Cerebral microbleeds (CMBs) are frequently observed in patients with cerebrovascular disease and Alzheimer's disease. CMBs that are located in the deep or infratentorial regions and those that are present strictly in the lobar regions reflect hypertensive vasculopathy and cerebral amyloid angiopathy, respectively. The development of CMBs can be accelerated by clinical factors. Orthostatic hypotension (OH) has been reported to be associated with cerebral small vessel disease, such as white matter lesions in Parkinson's disease (PD). We investigated the prevalence, location and risk factors, including OH, for CMBs in patients with PD. METHODS: We conducted a retrospective chart review of consecutive patients with PD who were admitted to the Department of Neurology, Juntendo University School of Medicine between January 2010 and July 2014. One hundred and sixty-seven patients with PD who underwent gradient echo T2*-weighted magnetic resonance imaging of the brain were included in the present study. A multivariate logistic regression analysis was performed to investigate the associations between risk factors and the presence of CMBs. RESULTS: CMBs were detected in 29 (17.4%) patients. Among the patients with CMBs, 19 (65.5%) had deep or infratentorial CMBs and 10 (34.5%) had strictly lobar CMBs. Hypertension, OH and a history of ischemic stroke were independently associated with deep or infratentorial CMBs, whereas antiplatelet use was independently associated with strictly lobar CMBs. CONCLUSIONS: In patients with PD, deep or infratentorial CMBs were more frequent than strictly lobar CMBs, and were associated with hypertension, OH and a history of ischemic stroke. PMID- 26142209 TI - [Quality of life after deep pelvic endometriosis surgery: Evaluation of a French version of the EHP-30]. AB - OBJECTIVE: To evaluate the changes in the quality of life of patients after deep pelvic endometriosis surgery, with a French version of EHP-30 questionnaire, and the capacity of the EHP-30 to carry out this measurement. MATERIAL AND METHODS: Study prospective monocentric, conducted in the obstetrics and gynecology department of the CHU Dijon during the period of October 2012 from October 2013. A EHP-30 questionnaire was given to patients before surgery. The same questionnaire was sent to their homes, away from surgery (3-6 months) to inform about their postoperative quality of life. The difference in preoperative and postoperative scores was tested using the test Wilcoxon signed ranks. A difference was considered significant if the p-value was less than or equal to 0.05. Sensitivity to change was calculated by the method of effect size (ES). The size of the effect is defined as the difference in mean preoperative and postoperative scores divided by the standard deviation of preoperative scores. A size effet of 0.20 indicates less change scores, of 0.50 a moderate change and of 0.80 a material change. RESULTS: We included 22 patients in total in the prospective analysis. The majority of patients had gynecological symptoms of dysmenorrhea with 69.7%, 75.7% and 75.7% dyspareunia chronic pelvic pain. Nineteen patients (57.6%) had gastro-intestinal symptoms. Urinary symptoms were less frequent. The results of the EHP-30 showed a significant improvement for the items "pain" (P=0.01), "control and powerlessness" (P=0.02), "emotional well being" (P<0,01) "social relations" (P<0.01), "sexual intercourse" (P=0.03) and "relationship with the medical world" (P=0.05). We observed a non-significant improvement for the items "self-image" (P=0.44), "work" (P=0.48) and "relationships with children" (P=0.50). The size of the effect (ES) was low to high for all dimensions of the questionnaire, ranging from 0.1 to 0.6 for the entire group. A significant sensitivity to change was found for the items "pain" (ES=0.60), "control and powerlessness" (ES=0.62), "social relations" (ES=0.57). A moderate sensitivity to change was found for the items "emotional well-being" (ES=0.29), "relationship with the medical world" (ES=0.26). A low sensitivity to change was found for the items "relationships with children" (ES=0.06), "self image" (ES=0.16), "work" (ES=0.18), "sexual intercourse" (ES=0.20). A size that is important to moderate effect corresponded to a statistically significant improvement of the score EHP-30. CONCLUSION: This study showed that the EHP-30 is a sensitive tool to change the health status and an appropriate instrument for the assessment of treatment effects in patients with deep pelvic endometriosis. PMID- 26142210 TI - [A review on tocolysis]. AB - Tocolytic agents have limited efficacy, delaying preterm delivery by 48 hours to 7 days, without any neonatal benefit. Cyclo-oxygenase inhibitors and calcium canal inhibitors seem to be the most efficient. Betamimetics are tocolytic agents with the highest incidence of severe maternal side effects. Oxytocin receptors antagonists and cyclo-oxygenase inhibitors are tocolytic agents with the best maternal tolerating profile. Nifedipin is the tocolytic agent presenting the best fetal tolerating profile. However, doubts persist on fetal and neonatal tolerance for cyclo-oxygenase inhibitors and probably even for oxytocin receptors antagonists. A combined or sequential tocolytic treatment did not prove superior to a single tocolytic treatment although the former is also associated with a high incidence of severe adverse maternal effects. Nevertheless, this low efficiency should not make us forget their major interest in case of premature labour: to allow the mother's in utero transfer to a level II or III maternity following the gestational age, and moreover to gain time so as to obtain an optimal interval for the fetal lung maturation by corticoid injection. Tocolytic agents should be used between 24(+0) and 34(+6)weeks of amenorrhea. They should be used on the short term (24 to 72 hours) owing to their short period of efficacy and to the risk of side effects that increases with the duration of use. PMID- 26142211 TI - [Obstetrical prognosis of breech presentation admitted in advanced first stage of labour]. AB - AIM: Fear of dystocia during breech delivery brings obstetrical teams to choose elective caesarean sections. However, some patients with breech presentations will be in labour before the date scheduled and caesarean delivery during labour increases maternal morbidity. Therefore, this situation raises the question about the relevance of labour trial for breech presentations admitted in labour. Our study aimed to determine the obstetrical prognosis of breech presentations on admission in the labour ward following their degree of cervical dilation. MATERIALS AND METHODS: We conducted an observational retrospective study on 213 single breech presentations at >=37 gestational weeks that delivered at our level 3 labour ward between1st January 2007 and 30th July 2013. Maternal, obstetrical and neonatal factors were analyzed. RESULTS: The total caesarean rate during labour was 23.4% and significantly less important (P<0.05) in patients with cervical dilation >=5cm on admission (14% vs. 27%). Apgar scores, cordonal arterial pH and lactates, rate of transfer to intensive care were not significantly different between the two groups. CONCLUSION: In our study, any patient with a breech presentation at an advanced stage of labour on admission is of very good prognosis, although statistical power is insufficient. PMID- 26142212 TI - [Is the stomach a main landmark on the abdominal circumference? Audit of 3 operators]. AB - OBJECTIVES: The fetal weight estimation depends largely on the accuracy of abdominal circumference. The quality criteria are standardized to minimize variability and include visualization of the stomach. The objective of this study is to investigate the presence or absence of the stomach on the abdominal circumference for 3 different operators. MATERIAL AND METHODS: We conducted re reading of 204 ultrasound images in the second and third trimester of pregnancy, performed by three operators, at the maternity Port Royal in Paris in 2013. On these images, the presence of the stomach was sought and other quality criteria were verified. RESULTS: Among the 204 images, 166 included the stomach (81%). When studying for each of the three operators, there were 79%, 72% and 98% of the stomach into the abdominal circumference, a significant difference between operators (P=0.0029). Regarding the secondary criteria, the quality criteria found most often were the calipers and well placed ellipse (89%). CONCLUSION: According to the previous studies, the stomach seems to be a reference to search. Our study shows variability depending on the different operators. If a hierarchy of quality criteria is to be considered, the stomach does not seem to be the first criterion to search. PMID- 26142213 TI - [An updated overview of the onco-gynecologic surgery in the French public hospitals: There, we are... but we are here!]. PMID- 26142214 TI - [The World Health Organisation proposes adopting the Robson Classification as an internationally applicable cesarean section classification system]. PMID- 26142215 TI - Forced fusion of human ventricular scar cells with cardiomyocytes suppresses arrhythmogenicity in a co-culture model. AB - AIMS: Fibrosis increases arrhythmogenicity in myocardial tissue by causing structural and functional disruptions in the cardiac syncytium. Forced fusion of fibroblastic cells with adjacent cardiomyocytes may theoretically resolve these disruptions. Therefore, the electrophysiological effects of such electrical and structural integration of fibroblastic cells into a cardiac syncytium were studied. METHODS AND RESULTS: Human ventricular scar cells (hVSCs) were transduced with lentiviral vectors encoding enhanced green fluorescent protein alone (eGFP?-hVSCs) or together with the fusogenic vesicular stomatitis virus G protein (VSV-G/eGFP?-hVSCs) and subsequently co-cultured (1:4 ratio) with neonatal rat ventricular cardiomyocytes (NRVMs) in confluent monolayers yielding eGFP?- and VSV-G/eGFP?-co-cultures, respectively. Cellular fusion was induced by brief exposure to pH = 6.0 medium. Optical mapping experiments showed eGFP?-co cultures to be highly arrhythmogenic [43.3% early afterdepolarization (EAD) incidence vs. 7.7% in control NRVM cultures, P < 0.0001], with heterogeneous prolongation of action potential (AP) duration (APD). Fused VSV-G/eGFP?-co cultures displayed markedly lower EAD incidence (4.6%, P < 0.001) than unfused co cultures, associated with decreases in APD, APD dispersion, and decay time of cytosolic Ca(2+) waves. Heterokaryons strongly expressed connexin43 (Cx43). Also, maximum diastolic potential in co-cultures was more negative after fusion, while heterokaryons exhibited diverse mixed NRVM/hVSC whole-cell current profiles, but consistently showed increased outward Kv currents compared with NRVMs or hVSCs. Inhibition of Kv channels by tetraethylammonium chloride abrogated the anti arrhythmic effects of fusion in VSV-G/eGFP?-co-cultures raising EAD incidence from 7.9 to 34.2% (P < 0.001). CONCLUSION: Forced fusion of cultured hVSCs with NRVMs yields electrically functional heterokaryons and reduces arrhythmogenicity by preventing EADs, which is, at least partly, attributable to increased repolarization force. PMID- 26142216 TI - Full quaternion based finite-time cascade attitude control approach via pulse modulation synthesis for a spacecraft. AB - In the aspect of further development of investigations in the area of spacecraft modeling and analysis of the control scheme, a new hybrid finite-time robust three-axis cascade attitude control approach is proposed via pulse modulation synthesis. The full quaternion based control approach proposed here is organized in association with both the inner and the outer closed loops. It is shown that the inner closed loop, which consists of the sliding mode finite-time control approach, the pulse width pulse frequency modulator, the control allocation and finally the dynamics of the spacecraft is realized to track the three-axis referenced commands of the angular velocities. The pulse width pulse frequency modulators are in fact employed in the inner closed loop to accommodate the control signals to a number of on-off thrusters, while the control allocation algorithm provides the commanded firing times for the reaction control thrusters in the overactuated spacecraft. Hereinafter, the outer closed loop, which consists of the proportional linear control approach and the kinematics of the spacecraft is correspondingly designed to deal with the attitude angles that are presented by quaternion vector. It should be noted that the main motivation of the present research is to realize a hybrid control method by using linear and nonlinear terms and to provide a reliable and robust control structure, which is able to track time varying three-axis referenced commands. Subsequently, a stability analysis is presented to verify the performance of the overall proposed cascade attitude control approach. To prove the effectiveness of the presented approach, a thorough investigation is presented compared to a number of recent corresponding benchmarks. PMID- 26142217 TI - Smooth integral sliding mode controller for the position control of Stewart platform. AB - This paper proposes the application of a new algorithm for the position control of a Stewart platform. The conventional integral sliding mode controller is a combination of nominal control and discontinuous feedback control hence the overall control is discontinuous in nature. The discontinuity in the feedback control is undesirable for practical applications due to chattering which causes the wear and tear of the mechanical actuators. In this paper the existing integral sliding mode control law for systems with matched disturbances is modified by replacing the discontinuous part by a continuous modified twisting control. This proposed controller is continuous in nature due to the combinations of two continuous controls. The desired position of the platform has been achieved using the proposed controller even in the presence of matched disturbances. The effectiveness of the proposed controller has been proved with the simulation results. PMID- 26142218 TI - High-order tracking differentiator based adaptive neural control of a flexible air-breathing hypersonic vehicle subject to actuators constraints. AB - In this paper, an adaptive neural controller is exploited for a constrained flexible air-breathing hypersonic vehicle (FAHV) based on high-order tracking differentiator (HTD). By utilizing functional decomposition methodology, the dynamic model is reasonably decomposed into the respective velocity subsystem and altitude subsystem. For the velocity subsystem, a dynamic inversion based neural controller is constructed. By introducing the HTD to adaptively estimate the newly defined states generated in the process of model transformation, a novel neural based altitude controller that is quite simpler than the ones derived from back-stepping is addressed based on the normal output-feedback form instead of the strict-feedback formulation. Based on minimal-learning parameter scheme, only two neural networks with two adaptive parameters are needed for neural approximation. Especially, a novel auxiliary system is explored to deal with the problem of control inputs constraints. Finally, simulation results are presented to test the effectiveness of the proposed control strategy in the presence of system uncertainties and actuators constraints. PMID- 26142219 TI - Quantifying intracellular metabolites in yeast using a matrix with minimal interference from naturally occurring analytes. AB - For quantification of intracellular metabolites, mass spectrometry combined with liquid chromatography, capillary electrophoresis, or gas chromatography is currently the method of choice, especially when combined with stable isotope labeled internal standards (SIL-ISs). Due to the difficulties in finding a biological matrix free of intracellular metabolites, a standard addition based validation is needed. Here, we present an alternative by producing a matrix with minimal signal interferences on both the analytes and their SIL-ISs. The matrix was obtained by cultivating Saccharomyces cerevisiae in [(13)C6]glucose/nonlabeled glucose (50:50, w/w) growth medium. The areas of both (12)C6 and (13)C6 fractions of ATP in the matrix were measured to be 2% of the sum of the areas of all ATP isotopes detected. The matrix allowed for spiking of both the nonlabeled and SIL-ISs and more straightforward validation. The intra- and inter-day accuracy and precision were ?80% and ?20%, respectively. The methodology was used for quantification of nucleotides, coenzymes, and redox compounds from Saccharomyces cerevisiae. The determined energy charge ratio was 0.9, whereas the Mal-CoA/Ac-CoA ratio was 0.04. The analysis of the redox compounds was challenging due to the oxidation of NADH and NADPH, when dissolved in water or tributylamine. The oxidation was reduced by dissolving them in ammonium acetate solution (pH 8.0). PMID- 26142220 TI - Microwave-assisted digestion combined with silica-based spin column for DNA isolation from human bones. AB - A protocol for the extraction of DNA from ancient skeletal material was developed. Bone specimen samples (powder or slice), buffer, pretreatment, and extraction methodologies were compared to investigate the best conditions yielding the highest concentration of DNA. The degree of extract contamination by polymerase chain reaction (PCR) inhibitors was compared as well. Pretreatment was carried out using agitation in an incubator shaker and microwave digestion. Subsequently, DNA from bones was isolated by the classical organic phenol chloroform extraction and silica-based spin columns. Decalcification buffer for total demineralization was required as well as lysis buffer for cell lysis to obtain DNA, whereas microwave-assisted digestion proved to be very rapid, with an incubation time of 2min instead of 24h at an incubator shaker without using lysis buffer. The correction of isolated DNA was detected using real-time PCR with melt curve analysis, which was 82.8+/-0.2 degrees C for highly repetitive alpha satellite gene region specific for human chromosome 17 (locus D17Z1). Consequently, microwave-based DNA digestion followed by silica column yielded a high-purity DNA with a concentration of 19.40ng/MUl and proved to be a superior alternative to the phenol-chloroform method, presenting an environmentally friendly and efficient technique for DNA extraction. PMID- 26142221 TI - An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma. AB - Osteosarcoma, the most common type of primary bone cancer, is the second highest cause of cancer-related death in pediatric patients. To understand the mechanisms behind osteosarcoma progression and to discover novel therapeutic strategies for this disease, a reliable and appropriate mouse model is essential. For this purpose, osteosarcoma cells need to be injected into the bone marrow. Previously, the intratibial and intrafemoral injection methods were reported; however, the major drawback of these methods is the potential leakage of tumor cells from the injection site during or after these procedures. To overcome this, we have established an improved method to minimize leakage in an orthotopic mouse model of osteosarcoma. By taking advantage of the anatomical benefits of the femur with less bowing and larger medullary cavity than those of the tibia, osteosarcoma cells are injected directly into the femoral cavity following reaming of its intramedullary space. To prevent potential leakage of tumor cells during and after the surgery, the injection site is sealed with bone wax. This method requires a minor surgery of approximately 15min under anesthesia. Our established orthotopic osteosarcoma model could serve as a valuable and reliable tool for examining progression of various types of bone tumors. PMID- 26142222 TI - Assay for drug discovery: Synthesis and testing of nitrocefin analogues for use as beta-lactamase substrates. AB - We report on the synthesis of three nitrocefin analogues and their evaluation as substrates for the detection of beta-lactamase activity. These compounds are hydrolyzed by all four Ambler classes of beta-lactamases. Kinetic parameters were determined with eight different beta-lactamases, including VIM-2, NDM-1, KPC-2, and SPM-1. The compounds do not inhibit the growth of clinically important antibiotic-resistant gram-negative bacteria in vitro. These chromogenic compounds have a distinct absorbance spectrum and turn purple when hydrolyzed by beta lactamases. One of these compounds, UW154, is easier to synthesize from commercial starting materials than nitrocefin and should be significantly less expensive to produce. PMID- 26142223 TI - Cystatin C: why clinical laboratories should be measuring it. AB - Cystatin C is a 13-kDa cysteine protease inhibitor that satisfies many of the criteria required of a marker of glomerular filtration rate. It can be readily measured in laboratories using automated, standardised immunoassays. Hitherto there has been reluctance to adopt cystatin C measurement in the assessment of kidney function, despite demonstrated superiority compared to the current standard of practice, serum creatinine. This may be due to increased direct reagent costs. Recent strong evidence has confirmed the superior ability of cystatin C compared to creatinine to predict risk of a range of poor outcomes (including kidney failure, cardiovascular events and mortality) among patients with chronic kidney disease. On the back of this, national and international guidelines including those of the National Institute for Health and Clinical Excellence have recommended the use of cystatin C to risk stratify individuals with mild to moderately reduced glomerular filtration rate and no albuminuria. Cystatin C presents an opportunity for laboratories to engage with their users in developing clinical pathways which will usefully focus chronic kidney disease management on those most likely to benefit while reassuring patients at low risk. PMID- 26142225 TI - Beneficial effects of Androctonus australis hector venom and its non-toxic fraction in the restoration of early hepatocyte-carcinogenesis induced by FB1 mycotoxin: Involvement of oxidative biomarkers. AB - Some venom components are known to present potential biological activities that are useful as tools in therapeutics. In this study anti-tumoral activity of Androctonus australis hector (Aah) venom and its purified fraction on early step of hepato-carcinogenesis initiated by Fumonisin (FB1), was tested. Initiated hepatic tumor was assessed in mice by decreased doses of Fumonisin B1 associated to phenobarbital. Scorpion venom was used to investigate its activity on initiated tumor by FB1. Evaluation of oxidative unbalance, enzymatic activities and DNA quantification in the liver were correlated with tissue analysis. Obtained results showed that the initiated pathogenesis by FB1 at seven months was characterized by tissue alterations and biomarker variations. These alterations were characterized by atypical lesions such as muffled nucleus, karyo and cyto-megaly; up normal and large number of nuclei into hepatocytes. These alterations were confirmed by DNA alteration. An unbalance of oxidative status was also observed, characterized by an increased levels of respectively oxidant (NO and MDA) and antioxidant (GSH and catalase activity) mediators. Aah venom and its non-toxic fraction used at low doses seemed to be able to restore partially the hepatic altered tissue induced by FB1. Decreased levels of oxidative and anti oxidative mediators were also observed. DNA in hepatocytes returned also to the physiological values. Structure of hepatic tissue showed restoration of some alterations such as karyo- and cyto-megaly; decrease of polyploidy hepatocytes induced by FB1. Aah venom and its non-toxic fraction seem to contain some bioactive components with anti-tumoral activity. Purification of this activity from non-toxic fraction F1 could be of interest to identify the components with anti-tumoral activities. PMID- 26142226 TI - [The role of the vitreous body in diseases of neighboring structures]. AB - BACKGROUND: The vitreoretinal interface is not merely the space between the vitreous body and the retina but it is also a site for highly complex pathologies with the vitreous body exerting an influence on all the neighbouring structures. METHODS: A literature search was performed in Pubmed and current book articles RESULTS: This review article highlights the role of the vitreous body in vitreomacular adhesion and traction, in the development of macular holes and epiretinal membranes as well as its role in age-related macular degeneration. In the retinal periphery the vitreous structures play a pivotal role in retinal tears and detachment as well as in diabetic and other proliferative vitreoretinopathies. The role of the vitreous bodyin the emergence of various forms of cataract is often underestimated. DISCUSSION: Vitreo-etinal surgeons should thoroughly understand the pathophysiological relationship between the vitreous body and the neighboring structures, especially in the era of medical vitreolysis. PMID- 26142227 TI - [Analysis of choroidal thickness in AP-ROP, threshold disease and ROP without laser photocoagulation]. AB - BACKGROUND: Enhanced depth imaging (EDI) and spectral domain optical coherence tomography (SD-OCT) provide high-definition cross-sectional images of the choroid. Information on alterations in choroidal thickness (CT) after laser photocoagulation (LC) in aggressive posterior retinopathy of prematurity (APROP) and threshold disease (TD) is rare. PATIENTS AND METHODS: A total of 75 eyes were retrospectively analyzed in 4 groups. Groups 1 and 2 included patients with APROP and TD, respectively, who underwent LC. Group 3 included ROP children who did not undergo LC and group 4 included full-term children. Infants aged >=4 < 7, who had examination of subfoveal (SF) CT with SD-EDI-OCT, visual acuity (VA), spherical equivalent (SE), anterior segment and fundus examination, axial lenght (AXL) were included. The results of SFCT, VA and SE at the age of >= 4 < 7 years, AXL, gestational age (GA), birth weight (BW) and age at examination were compared between the groups. Potential risk factors (GA, BW, SE, AXL and SFCT) influencing visual acuity were evaluated by using multivariate linear regression analysis. RESULTS: The results of SFCT and AXL were not significantly different between groups 2 and 3 or between groups 3 and 4. There was a significant difference between the other groups for SFCT and AXL and VA was significantly different between all groups. The SE was not significantly different between groups 3 and 4 but there was a significant difference for SE, BW and GA between the groups. Age at examination was not significantly different between the groups. Multivariate linear regression analysis revealed SFCT for groups 1 and 2, GA for group 3 and GA, SFCT and AXL for group 4 as independent risk factors influencing visual acuity. CONCLUSION: The regression model used for groups 1-4 explains the variation of the dependent risk factor LogMar VA for groups 1-4 with 31.2 %, 43.5 %, 9.6 % and 69.4 %, respectively. These values expressed in percentage demonstrate that even more predictors may influence the dependent factor LogMar VA than evaluated in the study. PMID- 26142224 TI - Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations. AB - Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and gamma aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain. PMID- 26142228 TI - [Sinus thrombosis and idiopathic intracerebral hypertension: Thrombophilia and hormonal influence as potentially relevant causal connections]. AB - BACKGROUND: Cerebral venous sinus thrombosis and idiopathic intracerebral hypertension (IIH) can lead to impaired vision, which is why the suspected diagnosis is often initially made by an ophthalmologist. PROBLEM AND AIMS: This study aimed at discovering common features between the two underlying conditions and provide ophthalmologists with concrete measures for differential diagnosis and for the management of affected patients based on these similarities. MATERIAL AND METHODS: This article presents detailed profiles of the underlying conditions and compares the two, focusing on similarities with respect to risk factors. RESULTS: The following common risk factor profiles of the two underlying conditions could be determined: (1) women before menopause, (2) administration of female hormones and (3) thrombophilia. DISCUSSION: Based on these findings at least a partial overlap of both pathophysiologies is suspected. In particular, undiagnosed cerebral thrombosis or microthrombosis can cause IIH. This mechanism could explain the typical thrombophilic risk profile of IIH, which is analogous to that of cerebral venous sinus thrombosis, including the well-established interaction of estrogens and thrombophilic risk factors. PMID- 26142229 TI - [Development of an ophthalmological clinical information system for inpatient eye clinics]. AB - BACKGROUND: In times of increased digitalization in healthcare, departments of ophthalmology are faced with the challenge of introducing electronic clinical health records (EHR); however, specialized software for ophthalmology is not available with most major EHR sytems. The aim of this project was to create specific ophthalmological user interfaces for large inpatient eye care providers within a hospitalwide EHR. Additionally the integration of ophthalmic imaging systems, scheduling and surgical documentation should be achieved. MATERIAL AND METHODS: The existing EHR i.s.h.med (Siemens, Germany) was modified using advanced business application programming (ABAP) language to create specific ophthalmological user interfaces for reproduction and moreover optimization of the clinical workflow. RESULTS: A user interface for documentation of ambulatory patients with eight tabs was designed. From June 2013 to October 2014 a total of 61,551 patient contact details were documented. For surgical documentation a separate user interface was set up. Digital clinical orders for documentation of registration and scheduling of operations user interfaces were also set up. A direct integration of ophthalmic imaging modalities could be established. CONCLUSION: An ophthalmologist-orientated EHR for outpatient and surgical documentation for inpatient clinics was created and successfully implemented. By incorporation of imaging procedures the foundation of future smart/big data analyses was created. PMID- 26142230 TI - [Central scotoma after viral prodrome]. AB - CASE REPORT: A 29-year-old female patient presented with a unilateral deterioration of visual acuity, metamorphopsia and a paracentral scotoma. The patient had suffered from a viral rhinitis 1 week prior to the ophthalmological symptoms. DIAGNOSTICS: Fundoscopy revealed parafoveal changes in the retinal pigment epithelium and spectral-domain optical coherence tomography (SD-OCT) disclosed corresponding hyperreflective, subretinal changes with disruption of Bruch's membrane and the outer limiting membrane. In the course of the disease there was a spontaneous regression of these changes. Visual acuity improved and the central scotoma resolved. The patient showed the typical history and clinical findings of unilateral acute idiopathic maculopathy. CONCLUSION: The most probable explanation for the patient's symptoms is an immunologically triggered adverse reaction due to a previous viral rhinitis, with participation of the retina and retinal pigment epithelium. As a rule the disease has a spontaneous and favorable course. PMID- 26142231 TI - [A 70-year-old patient with painful exophthalmos and double vision]. PMID- 26142232 TI - [Current aspects on treatment of congenital dacryostenosis]. PMID- 26142233 TI - [In Process Citation]. PMID- 26142234 TI - [Ligneous conjunctivitis]. AB - CASE REPORT: We report the case of a 3-year-old female patient with therapy refractive recurrent conjunctivitis and membrane formation of the upper eyelid. After surgical removal the histological examination showed an image compatible with ligneous conjunctivitis. A manifest serum plasminogen deficiency (22 %) supported the diagnosis. TREATMENT: The treatment with corticosteroids, heparin containing and fresh frozen plasma (FFP) eye drops, renewed surgical ablation with perioperative intravenous FFP administration and local cyclosporine A eye drops achieved a stable condition with low disease activity. CONCLUSION: The combination of these therapy approaches has been performed here for the first time and has not been described in the literature so far. PMID- 26142235 TI - "Talking About Chance": The Presentation of Risk Information During Genetic Counseling for Breast and Ovarian Cancer. AB - Using observations, questionnaires, and interviews, this study describes the formats used to present risk information during genetic counseling for breast and ovarian cancer. Counselees' preferences for different types of qualitative and quantitative presentation formats are also discussed. The data indicate that there is considerable variation in the presentation of risk information both within and between consultations. The counselees were positive about the way the counselors had described their risk. Seventy-three percent of the sample expressed a preference for risk to be described using quantitative formats, and there was little difference in the number who stated a preference for percentages, proportions, or population comparisons. Comparing preferred formats with those used in the consultations indicated that in over 40% of cases, risk information was not presented in the counselees' preferred quantitative format. This descriptive study raises questions about the presentation of risk information which warrant further research. PMID- 26142236 TI - Psychological Aspects of Genetic Counseling. IX. Teaching and Counseling. AB - The goals, philosophies, and procedures of the teaching and counseling approaches to genetic counseling are differentiated and compared. The teaching approach, inherited from academic practitioners earlier in this century, appears to remain the dominant form of contemporary practice. With the introduction of more nonphysician professionals, attempts are being made to combine a teaching model with counseling procedures. The goals of the two models are conspicuously different; one attempts to end up with an "educated" counselee whereas the other hopes to leave the latter psychologically more autonomous and functional. Both models have strengths and limitations. The teaching model is essentially a form of health education, not counseling, and, with some exceptions, tends to fulfill its goals. The strategy of teaching, however, tends to undermine the psychological self-directedness of counselees and thus interferes with the processes they need to draw on to make autonomous decisions. The strength of the counseling model is in helping counselees reach decisions and deal with the personal meaning of information. However, applying this model makes huge demands on the professional. Greater attention needs to be given by training programs to the pedagogical and counseling skills genetic counselors may need in their professional work. PMID- 26142238 TI - Genetic Library. PMID- 26142237 TI - An Oral History of the National Society of Genetic Counselors. AB - Master's level genetic counselors formed a professional society in 1979, 8 years after the first master's degree training program graduation. This paper presents an oral history of the early years of the National Society of Genetic Counselors (NSGC), reviews the symbiotic development and definition of a profession and a professional society, and discusses events and achievements attributed to the NSGC since its incorporation. This retrospective historical account is based on personal and collective oral history, NSGC archival material and other sources. PMID- 26142239 TI - Does oxytocin affect mind-reading? A replication study. AB - One of the most well-known findings in human oxytocin research is its beneficial effect on "mind-reading", i.e., inferring others' mental states just from the eye region in the Reading the Mind in the Eyes Test (RMET). Previous studies have partially confirmed these improvements and have further shown that they depend both on baseline social-emotional abilities and on specific item characteristics such as difficulty. Following the original design of Domes et al. (2007), the aim of the current study was to replicate and extend previous findings by thoroughly investigating the impact of oxytocin administration on RMET performance. We tested for potential moderation effects involving item difficulty, valence, intensity, sex of poser as well as individual differences in trait empathy measured with the Empathy Quotient (EQ) for a general score and the Interpersonal Reactivity Index (IRI) for a multidimensional assessment of cognitive and emotional empathy. Oxytocin did not affect mind-reading, neither in general nor when considering specific item characteristics. An association between oxytocin induced changes in RMET performance and emotional empathy (the empathic concern scale of the IRI) was evident, with individuals low in emotional empathy showing greater improvement after oxytocin administration compared to placebo. The reproducibility and variability of these and prior findings needs to be addressed in future experiments. As true effects may not replicate across different studies for various reasons, this should not discourage, but encourage further research. PMID- 26142240 TI - Life satisfaction moderates the impact of socioeconomic status on diurnal cortisol slope. AB - The association between SES and health is well established; however, only a handful of studies have investigated the relationship between SES and daily cortisol parameters. Further, within this small literature, virtually no studies have looked at psychological factors that might mitigate this relationship. In this study, we tested whether life satisfaction--the overall subjective affective assessment of one's own life--acts as a protective factor against cortisol dysregulation driven by low-SES. Among a large sample (N=1325) of individuals from the Midlife in the United States (MIDUS) survey, we found that low-SES individuals with high levels of life satisfaction had a cortisol circadian profile similar to those of high-SES individuals. In contrast, low-SES individuals reporting low life satisfaction experienced attenuated morning cortisol concentrations and a flatter ("less healthy") diurnal cortisol slope. Although more studies are needed to investigate the constellation of psychological resources and processes through which life satisfaction exerts its effects, the current work shows that the general affective evaluation of one's own life acts as a buffer against the detrimental effect of low-SES on health related physiological processes. PMID- 26142242 TI - Using in vitro structural alerts for chromosome damage to predict in vivo activity and direct future testing. AB - While the in vivo genotoxicity of a compound may not always correlate well with its activity in in vitro test systems, for certain compound classes a good overlap may exist between the two endpoints. The difficulty, however, lies in establishing the cases where this relationship holds true and selecting the most appropriate protocol to highlight any potential in vivo hazard. With this in mind, a project was initiated in which existing structural alerts for in vitro chromosome damage in the expert system Derek Nexus were assessed for their relevance to in vivo activity by assessing their predictivity against an in vivo chromosome damage data set. An expert assessment was then made of selected alerts. Information regarding the findings from specific in vivo tests was added to the alert along with any significant correlations between activity and test protocol or mechanism. A total of 32 in vitro alerts were updated using this method resulting in a significant improvement in the coverage of in vivo chromosome damage in Derek Nexus against a data set compiled by the mammalian mutagenicity study group of Japan. The detailed information relating to in vivo activity and protocol added to the alerts in combination with the mechanistic information provided will prove useful in directing the further testing of compounds of interest. PMID- 26142241 TI - Insomnia in women approaching menopause: Beyond perception. AB - The menopausal transition is marked by increased prevalence in disturbed sleep and insomnia, present in 40-60% of women, but evidence for a physiological basis for their sleep complaints is lacking. We aimed to quantify sleep disturbance and the underlying contribution of objective hot flashes in 72 women (age range: 43 57 years) who had (38 women), compared to those who had not (34 women), developed clinical insomnia in association with the menopausal transition. Sleep quality was assessed with two weeks of sleep diaries and one laboratory polysomnographic (PSG) recording. In multiple regression models controlling for menopausal transition stage, menstrual cycle phase, depression symptoms, and presence of objective hot flashes, a diagnosis of insomnia predicted PSG-measured total sleep time (p < 0.01), sleep efficiency (p = 0.01) and wakefulness after sleep onset (WASO) (p = 0.01). Women with insomnia had, on average, 43.5 min less PSG measured sleep time (p < 0.001). There was little evidence of cortical EEG hyperarousal in insomniacs apart from elevated beta EEG power during REM sleep. Estradiol and follicle stimulating hormone levels were unrelated to beta EEG power but were associated with the frequency of hot flashes. Insomniacs were more likely to have physiological hot flashes, and the presence of hot flashes predicted the number of PSG-awakenings per hour of sleep (p = 0.03). From diaries, women with insomnia reported more WASO (p = 0.002), more night-to-night variability in WASO (p < 0.002) and more hot flashes (p = 0.012) compared with controls. Women who develop insomnia in the approach to menopause have a measurable sleep deficit, with almost 50% of the sample having less than 6h of sleep. Compromised sleep that develops in the context of the menopausal transition should be addressed, taking into account unique aspects of menopause like hot flashes, to avoid the known negative health consequences associated with insufficient sleep and insomnia in midlife women. PMID- 26142243 TI - ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women. AB - Unlike its reported role in the cardiovascular diseases, little information is available for mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the cerebrovascular function. We investigated the different effects of ALDH2 genotypes on the risk of cerebral infarction between the genders, because different genders had different smoking and/or dinking status which are also risk factors for cerebral infarction. 247 healthy Chinese Han people (controls, group 1), 287 Chinese Han male patients with cerebral infarction (group 2), and 82 Chinese Han female patients with cerebral infarction (group 3) were involved in this study. The frequencies of the ALDH2*2 allele in group 3 were significantly higher than those in other groups (with P = 0.001 and P = 0.002, respectively). The difference of ALDH2*2 allele frequency between group 1 and group 2 was not significant (P = 0.652). After adjustment for smoking and drinking status, the male patients without smoking or drinking status (group 4) had higher ALDH2*2 allele frequency than group 1, but the difference was still not significant (P = 0.139). Thus, we conclude that ALDH2*2 allele may be a significant negative risk factor for cerebral infarction in Chinese women [odds ratio (OR) = 2.207, 95% CI 1.416-3.439]. But for Chinese male patients, the negative effects of ALDH2*2 allele on cerebral infarction which might be concealed by other risk factors were not significant. PMID- 26142244 TI - Study of sodium hyaluronate-based intranasal formulations containing micro- or nanosized meloxicam particles. AB - This article reports on the micro- and nanonization of meloxicam (MEL) with the aim of developing pre-dispersions as intermediates for the design of intranasal formulations. As a new approach, combined wet milling technology was developed in order to reduce the particle size of the MEL. Different milling times resulted in micro- or nanosized MEL in the pre-dispersions with polyvinyl alcohol as stabilizer agent, which were directly used for preparing intranasal liquid formulations with the addition of sodium hyaluronate as mucoadhesive agent. Reduction of the MEL particle size into the nano range led to increased saturation solubility and dissolution velocities, and increased adhesiveness to surfaces as compared with microsized MEL particles. A linear correlation was demonstrated between the specific surface area of MEL and the AUC. The in vitro and in vivo studies indicated that the longer residence time and the uniform distribution of nano MEL spray throughout an artificial membrane and the nasal mucosa resulted in better diffusion and a higher AUC. Nanosized MEL may be suggested for the development of an innovative dosage form with a different dose of the drug, as a possible administration route for pain management. PMID- 26142245 TI - Exploring the interaction between the antiallergic drug, tranilast and human serum albumin: Insights from calorimetric, spectroscopic and modeling studies. AB - The interaction of tranilast (TRN), an antiallergic drug with the main drug transporter in human circulation, human serum albumin (HSA) was studied using isothermal titration calorimetry (ITC), fluorescence spectroscopy and in silico docking methods. ITC data revealed the binding constant and stoichiometry of binding as (3.21 +/- 0.23) * 10(6)M(-1) and 0.80 +/- 0.08, respectively, at 25 degrees C. The values of the standard enthalpy change (DeltaH degrees ) and the standard entropy change (DeltaS degrees ) for the interaction were found as -25.2 +/- 5.1 kJ mol(-1) and 46.9 +/- 5.4 J mol(-1)K(-1), respectively. Both thermodynamic data and modeling results suggested the involvement of hydrogen bonding, hydrophobic and van der Waals forces in the complex formation. Three dimensional fluorescence data of TRN-HSA complex demonstrated significant changes in the microenvironment around the protein fluorophores upon drug binding. Competitive drug displacement results as well as modeling data concluded the preferred binding site of TRN as Sudlow's site I on HSA. PMID- 26142246 TI - Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion. AB - We present hot melt extrusion (HME) for the design of floating multiparticulates. Metoprolol succinate was selected as the model drug. Our foremost objective was to optimize the components Eudragit((r)) RS PO, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) to balance both buoyancy and controlled release. Gas generated by sodium bicarbonate in acidic medium was trapped in the polymer matrix to enable floating. Eudragit((r)) RS PO and PEO with sodium bicarbonate resulted in multiparticulates which exhibited rapid flotation within 3 min but inadequate total floating time (TFT) of 3h. Addition of HPMC to the matrix did not affect floating lag time (FLT), moreover TFT increased to more than 12h with controlled release of metoprolol succinate. Floating multiparticulates exhibited t50% of 5.24h and t90% of 10.12h. XRD and DSC analysis revealed crystalline state of drug while FTIR suggested nonexistence of chemical interaction between the drug and the other excipients. The assay, FLT, TFT and the drug release of the multiparticulates were unchanged when stored at 40 degrees C/75%RH for 3 months confirming stability. We present floating multiparticulates by HME which could be extrapolated to a range of other drugs. Our approach hence presents platform technology for floating multiparticulates. PMID- 26142247 TI - Size characterization of commercial micelles and microemulsions by Taylor dispersion analysis. AB - In this work, Taylor dispersion analysis was applied to the measurement of micelles (or microdroplets) molecular diffusion coefficient in micellar (or microemulsion) systems based on neutral/anionic/cationic or zwitterionic surfactants. The choice of the micellar marker and the influence the surfactant/marker concentrations on this determination are studied. Experimental results are compared to those derived from the literature using other experimental techniques. Taylor dispersion analysis, experienced in narrow capillaries, was found to be an efficient and suitable method for micelle (or microdroplet) size measurement due to: the low sample consumption, the absence of filtration requirement of the sample, the broad range of size determination (with no lower limit down to angstroms), the simplicity of the protocol, the possibility to measure the viscosity of surfactant solutions in given conditions and the determination of the weight-average micelle hydrodynamic radius. Application to the size-characterization of commercial microemulsions (Gelucire((r)) 44/14), used as an excipient in the pharmaceutical formulation, is provided with a comparison to DLS measurements. It was found that the polydispersity in size of the micelle did not influence the Gaussian peak shape of the taylorgram due to rapid surfactant exchange compared to the time-scale of the experiments (a few minutes). PMID- 26142248 TI - Design of controlled release systems for THEDES-Therapeutic deep eutectic solvents, using supercritical fluid technology. AB - Deep eutectic solvents (DES) can be formed by bioactive compounds or pharmaceutical ingredients. A therapeutic DES (THEDES) based on ibuprofen, a non steroidal anti-inflammatory drug (NSAID), and menthol was synthesized and its thermal behavior was analyzed by differential scanning calorimetry (DSC). A controlled drug delivery system was developed by impregnating a starch:poly epsilon-caprolactone polymeric blend (SPCL 30:70) with the menthol:ibuprofen THEDES in different ratios (10 and 20 wt%), after supercritical fluid sintering at 20 MPa and 50 degrees C. The morphological characterization of SPCL matrices impregnated with THEDES was performed by scanning electron microscopy (SEM) and micro-computed tomography (micro-CT). Drug release studies were carried out in a phosphate buffered saline. The results obtained provide important clues for the development of carriers for the sustainable delivery of bioactive compounds. PMID- 26142249 TI - Dimethyl silicone dry nanoemulsion inhalations: Formulation study and anti-acute lung injury effect. AB - Acute lung injury (ALI) is a severe disease, leading to death if not treated quickly. An emergency medicine is necessary for ALI therapy. Dimethyl silicone (DMS) is an effective agent to defoam the bubbles in the lung induced by ALI. However, DMS aerosols, a marketed formulation of DMS, affect environments and will be limited in the future. Here we firstly report a dry nanoemulsion inhalation for pulmonary delivery. Novel DMS dry nanoemulsion inhalations (DSNIs) were developed in this study. The optimal formulation of stable and homogenous DMS nanoemulsions (DSNs) was composed of Cremophor RH40/PEG 400/DMS (4:4:2, w/w/w) and water. The DSNs showed the tiny size of 19.8 nm, the zeta potential of -9.66 mV, and the low polydispersity index (PDI) of 0.37. The type of DSNs was identified as oil-in-water. The DSNs were added with mannitol followed by freeze drying to obtain the DSNIs that were loose white powders, showed good fluidity, and were capable of rapid reconstitution to DSNs. The DSNs could adhere on the surfaces of lyophilized mannitol crystals. The aerodynamic diameter of DSNIs was 4.82 MUm, suitable for pulmonary inhalation. The in vitro defoaming rate of DSNIs was 1.25 ml/s, much faster than those of the blank DSNIs, DMS, and DMS aerosols. The DSNIs showed significantly higher anti-ALI effect on the ALI rat models than the blank DSNIs and the DMS aerosols according to lung appearances, histological sections, and lung wet weight/dry weight ratios. The DSNIs are effective anti-ALI nanomedicines. The novel DMS formulation is a promising replacement of DMS aerosols. PMID- 26142250 TI - Novel missense mutation of the FAM83H gene causes retention of amelogenin and a mild clinical phenotype of hypocalcified enamel. AB - OBJECTIVE: Amelogenesis imperfecta (AI) is a group of clinically and genetically heterogeneous inherited conditions, causing alterations in the structure of enamel and chemical composition of enamel matrix during development. The objective of this study was to compare the clinical, radiographic, histological and immunohistochemical phenotypes of subjects affected with hypocalcified AI from three Chilean families and identify causal mutations in the FAM83H gene. DESIGN: The diagnosis was made using clinical, radiographic, histological and genealogical data from the patients, who were evaluated according to the classification criteria by Witkop. PCR and Sanger sequencing of the complete coding sequence and surrounding intron regions of the FAM83H gene were conducted. The structural study of the affected teeth was performed with light microscopy, scanning electron microscopy and immunohistochemistry. RESULTS: The probands of the three families were diagnosed with hypocalcified AI, but in only one of them the missense variant p.Gly557Cys was identified. This variant was not present in the SNP database or in 100 healthy controls and segregated with the disease in the affected family. Using light microscopy, a normal prismatic structure was observed in all three cases. However, the ultrastructure was found to be affected in two of the cases, showing persistence of organic matter including amelogenins. CONCLUSIONS: These results suggest that FAM83H missense mutation reported in one of the families analyzed in this study might cause a phenotype of hypocalcified enamel more attenuated with retention of amelogenin. PMID- 26142252 TI - Neuroligin 2 deletion alters inhibitory synapse function and anxiety-associated neuronal activation in the amygdala. AB - Neuroligin 2 (Nlgn2) is a synaptic adhesion protein that plays a central role in the maturation and function of inhibitory synapses. Nlgn2 mutations have been associated with psychiatric disorders such as schizophrenia, and in mice, deletion of Nlgn2 results in a pronounced anxiety phenotype. To date, however, the molecular and cellular mechanisms linking Nlgn2 deletion to psychiatric phenotypes remain completely unknown. The aim of this study was therefore to define the role of Nlgn2 in anxiety-related neural circuits. To this end, we used a combination of behavioral, immunohistochemical, and electrophysiological approaches in Nlgn2 knockout (KO) mice to expand the behavioral characterization of these mice and to assess the functional consequences of Nlgn2 deletion in the amygdala. Moreover, we investigated the differential activation of anxiety related circuits in Nlgn2 KO mice using a cFOS activation assay following exposure to an anxiogenic stimulus. We found that Nlgn2 is present at the majority of inhibitory synapses in the basal amygdala, where its deletion affects postsynaptic structures specifically at perisomatic sites and leads to impaired inhibitory synaptic transmission. Following exposure to an anxiogenic environment, Nlgn2 KO mice show a robust anxiety phenotype as well as exacerbated induction of cFOS expression specifically in CaMKII-positive projection neurons, but not in parvalbumin- or somatostatin-positive interneurons. Our data indicate that Nlgn2 deletion predominantly affects inhibitory synapses onto projection neurons in basal amygdala, resulting in decreased inhibitory drive onto these neurons and leading to their excessive activation under anxiogenic conditions. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. PMID- 26142251 TI - The immunogenetics of multiple sclerosis: A comprehensive review. AB - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and common cause of non-traumatic neurological disability in young adults. The likelihood for an individual to develop MS is strongly influenced by her or his ethnic background and family history of disease, suggesting that genetic susceptibility is a key determinant of risk. Over 100 loci have been firmly associated with susceptibility, whereas the main signal genome-wide maps to the class II region of the human leukocyte antigen (HLA) gene cluster and explains up to 10.5% of the genetic variance underlying risk. HLA-DRB1*15:01 has the strongest effect with an average odds ratio of 3.08. However, complex allelic hierarchical lineages, cis/trans haplotypic effects, and independent protective signals in the class I region of the locus have been described as well. Despite the remarkable molecular dissection of the HLA region in MS, further studies are needed to generate unifying models to account for the role of the MHC in disease pathogenesis. Driven by the discovery of combinatorial associations of Killer cell Immunoglobulin-like Receptor (KIR) and HLA alleles with infectious, autoimmune diseases, transplantation outcome and pregnancy, multi-locus immunogenomic research is now thriving. Central to immunity and critically important for human health, KIR molecules and their HLA ligands are encoded by complex genetic systems with extraordinarily high levels of sequence and structural variation and complex expression patterns. However, studies to-date of KIR in MS have been few and limited to very low resolution genotyping. Application of modern sequencing methodologies coupled with state of the art bioinformatics and analytical approaches will permit us to fully appreciate the impact of HLA and KIR variation in MS. PMID- 26142254 TI - Balloon-assisted packing of wide-neck aneurysms with a mixture of n-butyl cyanoacrylate, Lipiodol, and ethanol: an experimental study. AB - PURPOSE: To evaluate the feasibility of balloon-assisted packing with a mixture of n-butyl cyanoacrylate (NBCA), Lipiodol, and ethanol for wide-neck aneurysms. MATERIALS AND METHODS: Of 10 carotid aneurysms with wide necks created in a swine model, 3 aneurysms (long and short diameters 10.9 * 9.8 mm; neck width 8.3 +/- 1.2 mm (mean +/- SD)) and 7 aneurysms (11.2 * 9.5 mm; neck width 8.3 +/- 1.4 mm) were packed with a mixture of NBCA, Lipiodol, and ethanol in the ratios 1:1:0 (NL11) and 1:1:2 (NLE112), respectively. A microcatheter was advanced into the aneurysm and a balloon catheter was inflated at the aneurysm neck. Ten minutes after injection, the balloon catheter was deflated and its removal was attempted. RESULTS: For all three aneurysms in the NL11 group, the balloon catheter and the microcatheter adhered strongly to the vessel and could not be adjusted. For all seven aneurysms in the NLE112 group, both the balloon catheter and the microcatheter could be easily removed, which enabled successful full packing of the aneurysm by re-advancing the microcatheter and re-injecting NLE112 after re inflation of the balloon catheter. CONCLUSION: Although at a preliminary stage, balloon-assisted NLE injection is feasible for packing a wide-neck aneurysm. PMID- 26142255 TI - Modified Y-configured stents with the waffle-cone technique by use of Solitaire(r) stent for patients with wide-necked bifurcation aneurysms. AB - Endovascular treatment of wide-necked bifurcation aneurysms can be challenging, despite improvements in endovascular techniques. Y stent-assisted coiling is one such technique, but this may not be technically feasible, especially in cases of acute angulation between the proximal and distal parent arteries, and may require use of "modified Y-configured stents with the waffle-cone technique". We report three cases of wide-necked bifurcation aneurysms that were successfully treated by use of the Solitaire(r) stent. PMID- 26142253 TI - A therapeutic role for vitamin D on obesity-associated inflammation and weight loss intervention. AB - Vitamin D plays an essential role in the regulation of skeletal metabolism as well as calcium and phosphate homeostasis, while vitamin D receptor (VDR) regulates de novo lipid synthesis, thereby contributing to the development of obesity. Furthermore, obese individuals are at a greater risk for vitamin D deficiency which may increase the potential risk for chronic inflammation, insulin resistance, and metabolic syndrome. While acute exercise enhances the activation of inflammatory signaling pathways, chronic exercise training may attenuate elevated pro-inflammatory cytokine production, resulting in the improvement of cardiovascular and metabolic health in obese individuals. Supplementation with vitamin D coupled with exercise or mild caloric restriction has been shown to improve markers of fitness and inflammation as well as cholesterol. Therefore, this review primarily addresses the impact of vitamin D deficiency in obesity-related inflammatory imbalances and how exercise and weight loss interventions may enhance the beneficial effects on vitamin D-mediated inflammation in obesity. PMID- 26142256 TI - Patient-specific dose calculations for pediatric CT of the chest, abdomen and pelvis. AB - BACKGROUND: Organ dose is essential for accurate estimates of patient dose from CT. OBJECTIVE: To determine organ doses from a broad range of pediatric patients undergoing diagnostic chest-abdomen-pelvis CT and investigate how these relate to patient size. MATERIALS AND METHODS: We used a previously validated Monte Carlo simulation model of a Philips Brilliance 64 multi-detector CT scanner (Philips Healthcare, Best, The Netherlands) to calculate organ doses for 40 pediatric patients (M:F = 21:19; range 0.6-17 years). Organ volumes and positions were determined from the images using standard segmentation techniques. Non-linear regression was performed to determine the relationship between volume CT dose index (CTDIvol)-normalized organ doses and abdominopelvic diameter. We then compared results with values obtained from independent studies. RESULTS: We found that CTDIvol-normalized organ dose correlated strongly with exponentially decreasing abdominopelvic diameter (R(2) > 0.8 for most organs). A similar relationship was determined for effective dose when normalized by dose-length product (R(2) = 0.95). Our results agreed with previous studies within 12% using similar scan parameters (e.g., bowtie filter size, beam collimation); however results varied up to 25% when compared to studies using different bowtie filters. CONCLUSION: Our study determined that organ doses can be estimated from measurements of patient size, namely body diameter, and CTDIvol prior to CT examination. This information provides an improved method for patient dose estimation. PMID- 26142257 TI - Risk of Stroke and Cardiac Events in Medically Treated Asymptomatic Carotid Stenosis. AB - BACKGROUND: The risk of stroke in patients with 50% or more asymptomatic carotid stenosis (ACS) on intensive medical treatment is low. Hence, the optimal treatment of ACS remains controversial at this point of time. AIM: We assessed the risk of stroke/transient ischemic attack (TIA) and cardiac events in patients with 50% or more ACS on intensive medical treatment. METHODS: All patients with TIA/minor stroke (National Institutes of Health Stroke Scale score <=5) who had undergone vessel imaging as part of their evaluation and patients with coronary artery disease who had undergone vessel imaging before cardiac intervention were screened for the presence of asymptomatic carotid stenosis. The risk of TIA/stroke, cardiac events, and vascular deaths were evaluated. RESULTS: Of 1,800 patients, 92 patients (.05%) had ACS having 50% to 99% stenosis; 63 had TIA/minor stroke, and 29 had coronary artery disease, of whom 7 patients had bilateral ACS, thus constituting 99 study units of ACS. The mean follow-up was 34.7 months (range 3-120 months). Two patients developed ischemic events on the side ipsilateral to the ACS and 9 patients developed cardiac events during the follow up. The average annual event rate for cerebral ischemic events was .93% (95% confidence interval [CI], .11-3.37), 4.21% (95% CI, 1.92-7.98) for cardiac events, and 3.27% (95% CI, 1.31-6.74) for death. CONCLUSIONS: Although the risk of stroke in patients with ACS is low, acute coronary events and vascular deaths were significant. This highlights the importance of intensive risk factor modification to reduce adverse cardiovascular events in ACS rather than revascularization of the carotid stenosis. PMID- 26142258 TI - Transient Ischemic Attack Fast-track and Long-Term Stroke Risk: Role of Diffusion Weighted Magnetic Resonance Imaging. AB - BACKGROUND: Acute ischemic lesions on diffusion-weighted magnetic resonance imaging (DWI-MRI) are reliable predictors of recurrent stroke at 90 days. However, to date, limited information on transient ischemic attack (TIA) patients with positive DWI lesions for stroke risk from 1 to 5 years is available. In this study, we evaluated the role of positive DWI lesions and vascular risk factors on stroke, cardiovascular death, and mortality at 90 days (T0), 1 year (T1), and 5 years (T2). Moreover, we also evaluated the association between stroke risk and the presence of DWI lesions. METHODS: We performed an observational study on consecutive patients admitted to the emergency department of San Camillo Forlanini Hospital, Rome, Italy, from January 2007 to November 2012. Over the study period, 4300 patients with TIA or ischemic stroke were examined by stroke specialists in an emergency room setting within 1 hour from admittance. RESULTS: In 510 of 4300 patients (11.86%), a TIA was diagnosed, and 445 patients satisfy the study inclusion criteria. For all 445 patients, the mean ABCD2 score was 4.35 +/- 1.30. Using DWI-MRI, we identified acute ischemic lesions in 185 patients (41.57%). We did not observe any correlation between duration of symptoms, ABCD2 score, and positive or negative DWI lesions. Positivity for DWI was not associated with the presence of diabetes mellitus, hypertension, smoking habit, or age; however, an association with weakness was observed. We documented a time dependent increase in the absolute risk of stroke: T0: 1.35% (95% confidence interval [CI], .81-2.8); T1: 4.78% (95% CI, 2.88-7.47); T2: 9.02% (95% CI, 4.66 5.70). We did not record any difference in stroke risk in patients with positive DWI lesions: T0: hazard ratio [HR], 1.43; 95% CI, .35-5.88; log-rank P = .60; T1: HR, 1.04; 95%CI, .42-2.61; log-rank P = .91; T2: HR, .83; 95% CI, .25-2.67; log rank P = .86. CONCLUSIONS: This long-term follow-up study in TIA patients documents that both positive and negative DWI patients treated with fast-track had similar long-term risks of stroke. PMID- 26142259 TI - Stroke-Like Episodes Heralding a Reversible Encephalopathy: Microbleeds as the Key to the Diagnosis of Cerebral Amyloid Angiopathy-Related Inflammation-A Case Report and Literature Review. AB - BACKGROUND: Cerebral amyloid angiopathy (CAA) is a common, often asymptomatic disease. Lobar intracerebral hemorrhage is the most frequent manifestation of CAA. Nevertheless, presentation of CAA with subacute cognitive decline, seizures, or headache with concomitant hyperintensities on T2-weighted magnetic resonance imaging (MRI) sequences and neuropathologic evidence of inflammation has been described. This disorder is known as CAA-related inflammation (CAA-ri). METHODS: Description of a stroke-like presentation of CAA-ri and systematic review of case reports and case series of CAA-ri. RESULTS: A 75-year-old woman with a history of atrial fibrillation, and a transient episode of aphasia 2 days before, presented in the emergency room with sudden onset aphasia. Brain computed tomography disclosed a left temporal hypodensity. A diagnosis of probable stroke was given. During the following days, there was a progressive clinical deterioration. MRI revealed coalescent edematous white matter lesion, hyperintense on T2-weighted sequences, and multiple lobar microbleeds on T2*-weighted sequences. A diagnosis of CAA-ri was considered, and the patient was started on steroids with clinical and imaging improvement. From our systematic review, microbleeds were present in almost 90% of patients with CAA-ri. CONCLUSIONS: Imaging findings associated with CAA-ri allow the early diagnosis and treatment of this potentially reversible disorder. Aside from the most common subacute presentations, CAA-ri can have a stroke-like presentation and be a stroke mimic. PMID- 26142260 TI - Causes and Predictors for Hospital Readmission after Ischemic Stroke. AB - BACKGROUND: Readmission after stroke is frequent, but limited data are available in Europe. This study aimed at assessing frequencies, causes, and factors associated with early and late unplanned readmissions within 1 year after discharge from ischemic stroke hospitalization. METHODS: All surviving ischemic stroke patients admitted to the Department of Neurology, Haukeland University Hospital, Norway, between July 1, 2007, and June 30, 2012, were followed from discharge until August 1, 2012. Information on readmissions was collected by medical chart reviews. Logistic regression was performed to assess factors associated with early (<=90 days) and late (91-365 days) readmission. RESULTS: Of 1175 patients discharged alive, 18.8% were readmitted within 90 days, and 24.5% were readmitted between day 91 and 365. Most frequent causes were infections, recurrent ischemic stroke, other cardiovascular events, and events related to index stroke. Early readmission was associated with older age, impaired physical function, atherosclerotic etiology of index stroke, and a higher risk factor burden. Late readmission was associated with older age and prior myocardial infarction. Early readmitted patients had shorter length of index admission, poorer physical function and higher frequencies of atherosclerotic etiology of index stroke, atrial fibrillation, and complications with infection during the index admission compared to patients readmitted late. CONCLUSIONS: Readmission after ischemic stroke is frequent, especially in the early period after discharge. Diagnoses and predictors varied according to time point for readmission, reflecting different underlying mechanisms for causes of readmission. Causes of early readmission may include a prothrombotic state and disposition for recurrent infections. PMID- 26142261 TI - Potential Augmentation of the Risk of Ischemic Cerebrovascular Accident by Chronic Obstructive Pulmonary Disease in Patients with Atrial Fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) is a potent risk factor for ischemic cerebrovascular accident (ICVA). Inflammation is a potential pathogenic factor for atherosclerosis and ICVA. Chronic obstructive pulmonary disease (COPD) is associated with increased inflammatory markers. Subjects who frequently experience COPD and AF together may have higher risk of ICVA. The objective of the study is to compare the prevalence of ICVA in patients with atrial fibrillation and COPD together versus atrial fibrillation alone. METHODS: Subjects diagnosed with COPD, AF, and ICVA were categorized into 3 groups: COPD, AF, and COPD plus AF. Prevalence of ICVA was compared. Confounding factors affecting ICVA risk were recorded: age, diabetes, hypertension, peripheral vascular disease, dyslipidemia, and congestive cardiac failure. RESULTS: Total charts reviewed were 500: COPD alone 244, AF alone 188, and both together 68. ICVA was documented in 132 (26.4%) subjects. Prevalence of ICVA was 11.8% (COPD alone), 29.8% (AF alone), and 39.7% (AF plus COPD). COPD plus AF group had ICVA 2.05 (95% confidence interval [CI], 1.203-3.94; P = .007) times compared with others. ICVA was also higher in patients with AF only versus COPD only (P < .001). Logistic regression showed AF plus COPD was a stronger predictor of ICVA (P = .001) than AF only (P = .07) or COPD only (P = .8). Odds ratio for ICVA was 2.85 (CI, 1.57-5.16; P = .001) for AF plus COPD versus 1.81 (CI, .94-3.47; P = .71) for AF only and 1.08 (CI, .58-2.10; P = .8) for COPD only. CONCLUSIONS: COPD may increase the risk of ischemic stroke in subjects with AF. Presence of COPD may increase the risk of ischemic stroke in subjects with AF. PMID- 26142262 TI - Development and Evaluation of a Decision Aid About Prenatal Testing for Women of Advanced Maternal Age. AB - OBJECTIVE: To develop and evaluate a decision aid designed to prepare patients of advanced maternal age for counseling about prenatal diagnostic testing. SETTING: A regional genetics center. DESIGN: A before/after study. INTERVENTIONS: Participants used an audioguided workbook to learn about options and outcomes and to clarify personal risks, values, questions, and predispositions. SUBJECTS: 21 women of advanced maternal age and 17 spouses. MAIN OUTCOME MEASURES: Knowledge of prenatal testing alternatives, decisional conflict, level of anxiety, and acceptability of the decision aid. RESULTS: After using the decision aid, participants had significantly reduced decisional conflict (uncertainty) and a significant increase in knowledge. There was no effect on state or trait anxiety. More than three-quarters of participants were satisfied with the length, clarity, balance, and acceptability of the decision aid. CONCLUSIONS: The decision aid shows promise as a useful aid for preparing couples for counseling. PMID- 26142264 TI - Genetic Library. PMID- 26142263 TI - Case Report: Object Relations Family Therapy as a Model for Genetic Counseling. AB - Object relations family therapy (ORFT) is a psychoanalytically based approach for the treatment of couples and families which stresses the importance of past relationships. The therapist assumes a parentlike role and provides a holding environment in which clients can explore unconscious motivations. This paper will discuss the applicability of this method to genetic counseling. The case of a couple seen for recurrent trisomies will be presented and used as an example to discuss how ORFT might serve as a framework in a genetic counseling session. PMID- 26142265 TI - Abstracts from the Twenty-First Annual Education Conference of the National Society of Genetic Counselors (Phoenix, Arizona, November 2002). PMID- 26142266 TI - [Baseline characteristics and changes in treatment after a period of optimization of the patients included in the study EFICAR]. AB - OBJECTIVES: To describe the baseline date and drugs therapy changes during treatment optimization in patients with heart failure with depressed systolic function included in the EFICAR study. DESIGN: Multicenter randomized clinical trial. LOCATION: Seven Health Centers. PARTICIPANTS: 150 patients (ICFSD) age 68+/-10 years, 77% male. MEASUREMENTS: Sociodemographic variables, comorbidities (Charlson index), functional capacity and quality of life. Drug therapy optimization was performed. RESULTS: The main etiology was ischemic heart disease (45%), with 89% in functional class II. The Charlson index was 2.03+/-1.05. The ejection fraction mean was 37%+/-8, 19% with ejection fraction <30%. With the stress test 6.3+/-1.6 mean was reached, with the 6 minutes test 446+/-78 meters and the chair test 13.7+/-4.4 seconds. The overall quality of life with ejection fraction was 22.8+/-18.7 and with the Short Form-36 Health Survey, physical health 43.3+/-8.4 and mental health 50.1+/-10.6. After optimizing the treatment, the percentage of patients on drugs therapy and the dose of angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and beta blockers were not changed. CONCLUSIONS: The majority of the subjects are in functional class II, with functional capacity and quality of life decreased and comorbidity index high. A protocolized drug therapy adjustment did not increase the dose or number of patients with effective drugs for heart failure with depressed systolic function. PMID- 26142267 TI - Impact of daily anatomical changes on EPID-based in vivo dosimetry of VMAT treatments of head-and-neck cancer. AB - BACKGROUND AND PURPOSE: Target dose verification for VMAT treatments of head-and neck (H&N) cancer using 3D in vivo EPID dosimetry is expected to be affected by daily anatomical changes. By including these anatomical changes through cone-beam CT (CBCT) information, the magnitude of this effect is investigated. MATERIALS AND METHODS: For 20 VMAT-treated H&N cancer patients, all plan-CTs (pCTs), 633 CBCTs and 1266 EPID movies were used to compare four dose distributions per fraction: treatment planning system (TPS) calculated dose and EPID reconstructed in vivo dose, both determined using the pCT and using the CBCT. D2, D50 and D98 of the planning target volume (PTV) were determined per dose distribution. RESULTS: When including daily anatomical information, D2, D50 and D98 of the PTV change on average by 0.0+/-0.4% according to TPS calculations; the standard deviation of the difference between EPID and TPS target dose changes from 2.5% (pCT) to 2.1% (CBCT). Small time trends are seen for both TPS and EPID dose distributions when using the pCT, which disappear when including CBCT information. CONCLUSIONS: Daily anatomical changes hardly influence the target dose distribution for H&N VMAT treatments according to TPS recalculations. Including CBCT information in EPID dose reconstructions slightly improves the agreement with TPS calculations. PMID- 26142268 TI - Predicting the need for adaptive radiotherapy in head and neck cancer. AB - BACKGROUND AND PURPOSE: Adaptive radiotherapy (ART) can account for the dosimetric impact of anatomical change in head and neck cancer patients; however it can be resource intensive. Consequently, it is imperative that patients likely to require ART are identified. The purpose of this study was to find predictive factors that identify oropharyngeal squamous cell carcinoma (OPC) and nasopharyngeal carcinoma (NPC) patients more likely to need ART. MATERIALS AND METHODS: One hundred and ten patients with OPC or NPC were analysed. Patient demographics and tumour characteristics were compared between patients who were replanned and those that were not. Factors found to be significant were included in logistic regression models. Risk profiles were developed from these models. A dosimetric analysis was performed. RESULTS: Nodal disease stage, pre-treatment largest involved node size, diagnosis and initial weight (categorised in 2 groups) were identified as significant for inclusion in the model. Two models were found to be significant (p=0.001), correctly classifying 98.2% and 96.1% of patients respectively. Three ART risk profiles were developed. CONCLUSION: Predictive factors identifying OPC or NPC patients more likely to require ART were reported. A risk profile approach could facilitate the effective implementation of ART into radiotherapy departments through forward planning and appropriate resource allocation. PMID- 26142269 TI - Atlas of the thoracic lymph nodal delineation and recommendations for lymph nodal CTV of esophageal squamous cell cancer in radiation therapy from China. AB - PURPOSE: To construct an anatomical atlas of thoracic lymph node regions of esophageal cancer (EC) based on definitions from The Japan Esophageal Society (JES) and generate a consensus to delineate the nodal clinical target volume (CTVn) for elective nodal radiation (ENI) of esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: An interdisciplinary group including two dedicated radiation oncologists, an experienced radiologist, a pathologist and two thoracic surgeons were gathered to generate a three-dimensional radiological description for the mediastinal lymph node regions of EC on axial CT scans. Then the radiological boundaries of lymph node regions were validated by a relatively large number of physicians in multiple institutions. RESULTS: An atlas of detailed anatomic boundaries of lymph node station No. 105-114 was defined on axial CT, along with illustrations. From the previous work, the study provided a guide of CTVn contouring for ENI of thoracic ESCC from a single center. CONCLUSION: It is feasible to use such an atlas of thoracic lymph node stations for radiotherapy planning. A phase III study based on the atlas is ongoing in China to measure quantitatively the ENI received by patients with ESCC. PMID- 26142270 TI - Functional specialization of the male insula during taste perception. AB - The primary gustatory area is located in the insular cortex. Although the insular cortex has been the topic of multiple parcellation studies, its functional specialization regarding taste processing received relatively little attention. Studies investigating the brain response to taste suggested that the insular cortex is involved in processing multiple characteristics of a taste stimulus, such as its quality, intensity, and pleasantness. In the current functional magnetic resonance study, younger and older adult male subjects were exposed to four basic tastes in five increasing concentrations. We applied a data-driven analysis to obtain insular response maps, which showed that the insular cortex processes the presence of taste, its corresponding pleasantness, as well as its concentration. More specifically, the left and right insular cortices are differentially engaged in processing the aforementioned taste characteristics: representations of the presence of a taste stimulus as well as its corresponding pleasantness dominate in the left insular cortex, whereas taste concentration processing dominates in the right insular cortex. These results were similar across both age groups. Our results fit well within previous cytoarchitectural studies and show insular lateralization in processing different aspects of taste stimuli in men. PMID- 26142272 TI - Deformation field correction for spatial normalization of PET images. AB - Spatial normalization of positron emission tomography (PET) images is essential for population studies, yet the current state of the art in PET-to-PET registration is limited to the application of conventional deformable registration methods that were developed for structural images. A method is presented for the spatial normalization of PET images that improves their anatomical alignment over the state of the art. The approach works by correcting the deformable registration result using a model that is learned from training data having both PET and structural images. In particular, viewing the structural registration of training data as ground truth, correction factors are learned by using a generalized ridge regression at each voxel given the PET intensities and voxel locations in a population-based PET template. The trained model can then be used to obtain more accurate registration of PET images to the PET template without the use of a structural image. A cross validation evaluation on 79 subjects shows that the proposed method yields more accurate alignment of the PET images compared to deformable PET-to-PET registration as revealed by 1) a visual examination of the deformed images, 2) a smaller error in the deformation fields, and 3) a greater overlap of the deformed anatomical labels with ground truth segmentations. PMID- 26142273 TI - The effect of Gibbs ringing artifacts on measures derived from diffusion MRI. AB - Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a unique method to investigate microstructural tissue properties noninvasively and is one of the most popular methods for studying the brain white matter in vivo. To obtain reliable statistical inferences with diffusion MRI, however, there are still many challenges, such as acquiring high-quality DW-MRI data (e.g., high SNR and high resolution), careful data preprocessing (e.g., correcting for subject motion and eddy current induced geometric distortions), choosing the appropriate diffusion approach (e.g., diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), or diffusion spectrum MRI), and applying a robust analysis strategy (e.g., tractography based or voxel based analysis). Notwithstanding the numerous efforts to optimize many steps in this complex and lengthy diffusion analysis pipeline, to date, a well-known artifact in MRI--i.e., Gibbs ringing (GR)--has largely gone unnoticed or deemed insignificant as a potential confound in quantitative DW-MRI analysis. Considering the recent explosion of diffusion MRI applications in biomedical and clinical applications, a systematic and comprehensive investigation is necessary to understand the influence of GR on the estimation of diffusion measures. In this work, we demonstrate with simulations and experimental DW-MRI data that diffusion estimates are significantly affected by GR artifacts and we show that an off-the-shelf GR correction procedure based on total variation already can alleviate this issue substantially. PMID- 26142271 TI - SchizConnect: Mediating neuroimaging databases on schizophrenia and related disorders for large-scale integration. AB - SchizConnect (www.schizconnect.org) is built to address the issues of multiple data repositories in schizophrenia neuroimaging studies. It includes a level of mediation--translating across data sources--so that the user can place one query, e.g. for diffusion images from male individuals with schizophrenia, and find out from across participating data sources how many datasets there are, as well as downloading the imaging and related data. The current version handles the Data Usage Agreements across different studies, as well as interpreting database specific terminologies into a common framework. New data repositories can also be mediated to bring immediate access to existing datasets. Compared with centralized, upload data sharing models, SchizConnect is a unique, virtual database with a focus on schizophrenia and related disorders that can mediate live data as information is being updated at each data source. It is our hope that SchizConnect can facilitate testing new hypotheses through aggregated datasets, promoting discovery related to the mechanisms underlying schizophrenic dysfunction. PMID- 26142274 TI - On the importance of electrode parameters for shaping electric field patterns generated by tDCS. AB - Transcranial direct current stimulation (tDCS) uses electrode pads placed on the head to deliver weak direct current to the brain and modulate neuronal excitability. The effects depend on the intensity and spatial distribution of the electric field. This in turn depends on the geometry and electric properties of the head tissues and electrode pads. Previous numerical studies focused on providing a reasonable level of detail of the head anatomy, often using simplified electrode models. Here, we explore via finite element method (FEM) simulations based on a high-resolution head model how detailed electrode modeling influences the calculated electric field in the brain. We take into account electrode shape, size, connector position and conductivities of different electrode materials (including saline solutions and electrode gels). These factors are systematically characterized to demonstrate their impact on the field distribution in the brain. The goals are to assess the effect of simplified electrode models; and to develop practical rules-of-thumb to achieve a stronger stimulation of the targeted brain regions underneath the electrode pads. We show that for standard rectangular electrode pads, lower saline and gel conductivities result in more homogeneous fields in the region of interest (ROI). Placing the connector at the center of the electrode pad or farthest from the second electrode substantially increases the field strength in the ROI. Our results highlight the importance of detailed electrode modeling and of having an adequate selection of electrode pads/gels in experiments. We also advise for a more detailed reporting of the electrode montages when conducting tDCS experiments, as different configurations significantly affect the results. PMID- 26142275 TI - Striatal and thalamic GABA level concentrations play differential roles for the modulation of response selection processes by proprioceptive information. AB - The selection of appropriate responses is a complex endeavor requiring the integration of many different sources of information in fronto-striatal-thalamic circuits. An often neglected but relevant piece of information is provided by proprioceptive inputs about the current position of our limbs. This study examines the importance of striatal and thalamic GABA levels in these processes using GABA-edited magnetic resonance spectroscopy (GABA-MRS) and a Simon task featuring proprioception-induced interference in healthy subjects. As a possible model of deficits in the processing of proprioceptive information, we also included Parkinson's disease (PD) patients in this study. The results show that proprioceptive information about unusual postures complicates response selection processes in controls, but not in PD patients. The well-known deficits of PD patients in processing proprioceptive information can turn into a benefit when altered proprioceptive information would normally complicate response selection processes. Striatal and thalamic GABA levels play dissociable roles in the modulation of response selection processes by proprioceptive information: Striatal GABA levels seem to be important for the general speed of responding, most likely because striatal GABA promotes response selection. In contrast, the modulation of response conflict by proprioceptive information is closely related to thalamic GABA concentrations with higher concentration being related to a smaller response conflict effect. The most likely explanation for this finding is that the thalamus is involved in the integration of sensorimotor, attentional, and cognitive information for the purpose of response formation. Yet, this effect in the thalamus vanishes when controls and PD patients were analyzed separately. PMID- 26142276 TI - Local and remote thermoregulatory changes affect NIRS measurement in forearm muscles. AB - PURPOSE: Near infrared spectroscopy (NIRS) assessment in skeletal muscle is potentially affected by circulatory changes occurring in superficial tissues. The aim of this study was to separately assess the interference from skin microcirculation and large vein blood flow by investigating the effect of selective local and remote warming-induced vasodilation, respectively. METHODS: Blood volume and oxygenation changes were investigated in the forearm muscles of healthy subjects in two experimental series (ES) during selective forearm (ES1, n = 12) or hand warming (ES2, n = 10). In ES1, the response to muscle contraction (10 s, 70 % MVC) and occlusion before and after warming was also investigated, while in ES2 two NIRS probes were expressly positioned over a visible vein and over a vein-free area. RESULTS: Local warming increased the modified Beer-Lambert (BL) blood volume indicator, tHb, by 5.3 +/- 3.6 umol/L cm to an extent comparable to post-contraction hyperemia (6.8 +/- 2.9 umol/L cm, p < 0.01). Remote warming increased skin blood flow at the hand and tHb at both forearm sites (on average: 5.4 +/- 4.8 umol/L cm, p < 0.01). Conversely, indicators of blood volume and oxygenation, based on spatially resolved spectroscopy (SRS), were not affected by any of the warming stimuli. CONCLUSIONS: These results demonstrate for the first time that: (1) blood drained by superficial veins may affect BL measurement; (2) it is difficult to exclude veins from the measurement by simple visual inspection of the cutaneous surface; (3) SRS effectively rejects artifacts from superficial hemodynamic changes in both cutaneous microcirculation and large veins. These results bear implications to conditions in which thermoregulatory adjustments cannot be excluded. PMID- 26142277 TI - Haemodynamics of aerobic and resistance blood flow restriction exercise in young and older adults. AB - PURPOSE: Light-load blood flow restriction exercise (BFRE) may provide a novel training method to limit the effects of age-related muscle atrophy in older adults. Therefore, the purpose of this study was to compare the haemodynamic response to resistance and aerobic BFRE between young adults (YA; n = 11; 22 +/- 1 years) and older adults (OA; n = 13; 69 +/- 1 years). METHOD: On two occasions, participants completed BFRE or control exercise (CON). One occasion was leg press (LP; 20 % 1-RM) and the other was treadmill walking (TM; 4 km h(-1)). Haemodynamic responses (HR, Q, SV and BP) were recorded during baseline and exercise. RESULT: At baseline, YA and OA were different for some haemodynamic parameters (e.g. BP, SV). The relative responses to BFRE were similar between YA and OA. Blood pressures increased more with BFRE, and also for LP over TM. Q increased similarly for BFRE and CON (in both LP and TM), but with elevated HR and reduced SV (TM only). CONCLUSION: While BFR conferred slightly greater haemodynamic stress than CON, this was lower for walking than leg-press exercise. Given similar response magnitudes between YA and OA, these data support aerobic exercise being a more appropriate BFRE for prescription in older adults that may contribute to limiting the effects of age-related muscle atrophy. PMID- 26142278 TI - High-Frequency Ultrasound for the Study of Early Mouse Embryonic Cardiovascular System. AB - An accurate diagnosis of congenital heart defects during fetal development is critical for interventional planning. Mice can be used to generate animal models with heart defects, and high-frequency ultrasound (HFUS) imaging enables in utero imaging of live mouse embryos. A wide range of physiological measurements is possible using Doppler-HFUS imaging; limitations of any single measurement warrant a multiparameter approach to characterize cardiovascular function. Doppler-HFUS was used to explore the embryonic (heart, aorta) and extraembryonic (umbilical blood flow) circulatory systems to create a database in normal mouse embryos between 9.5 and 16.5 days of gestation. Multivariate analyses were performed to explore correlations between gestational age and embryo echocardiographic parameters. Heart rate and peak velocity in the aorta were positively correlated with gestational time, whereas cardiac cycle length, isovolumetric relaxation time, myocardial performance index, and arterial deceleration time of the umbilical cord were negatively correlated with it. Doppler-HFUS facilitated detailed characterization of the embryonic mouse circulation and represents a useful tool for investigation of the early mouse embryonic cardiovascular system. PMID- 26142279 TI - Removal of H2A.Z by INO80 promotes homologous recombination. AB - The mammalian INO80 remodelling complex facilitates homologous recombination (HR), but the mechanism by which it does this is unclear. Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. H2A.Z is actively incorporated at sites of damage in mammalian cells, raising the possibility that H2A.Z may need to be subsequently removed for resolution of repair. Here, we show that H2A.Z in human cells is indeed rapidly removed from chromatin flanking DNA damage by INO80. We also report that the histone chaperone ANP32E, which is implicated in removing H2AZ from chromatin, similarly promotes HR and appears to work on the same pathway as INO80 in these assays. Importantly, we demonstrate that the HR defect in cells depleted of INO80 or ANP32E can be rescued by H2A.Z co-depletion, suggesting that H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting homologous recombination. PMID- 26142280 TI - Phosphorylation of ubiquitin at Ser65 affects its polymerization, targets, and proteome-wide turnover. AB - Ubiquitylation is an essential post-translational modification that regulates numerous cellular processes, most notably protein degradation. Ubiquitin can itself be phosphorylated at nearly every serine, threonine, and tyrosine residue. However, the effect of this modification on ubiquitin function is largely unknown. Here, we characterized the effects of phosphorylation of yeast ubiquitin at serine 65 in vivo and in vitro. We find this post-translational modification to be regulated under oxidative stress, occurring concomitantly with the restructuring of the ubiquitin landscape into a highly polymeric state. Phosphomimetic mutation of S65 recapitulates the oxidative stress phenotype, causing a dramatic accumulation of ubiquitylated proteins and a proteome-wide reduction of protein turnover rates. Importantly, this mutation impacts ubiquitin chain disassembly, chain linkage distribution, ubiquitin interactions, and substrate targeting. These results demonstrate that phosphorylation is an additional mode of ubiquitin regulation with broad implications in cellular physiology. PMID- 26142282 TI - Examining the attitudes of hospital pharmacists to reporting medication safety incidents using the theory of planned behaviour. AB - OBJECTIVE: To assess the effect of factors within hospital pharmacists' practice on the likelihood of their reporting a medication safety incident. DESIGN: Theory of planned behaviour (TPB) survey. SETTING: Twenty-one general and teaching hospitals in the North West of England. PARTICIPANTS: Two hundred and seventy hospital pharmacists (response rate = 45%). INTERVENTION: Hospital pharmacists were invited to complete a TPB survey, based on a prescribing error scenario that had resulted in serious patient harm. Multiple regression was used to determine the relative influence of different TPB variables, and participant demographics, on the pharmacists' self-reported intention to report the medication safety incident. MAIN OUTCOME MEASURES: The TPB variables predicting intention to report: attitude towards behaviour, subjective norm, perceived behavioural control and descriptive norm. RESULTS: Overall, the hospital pharmacists held strong intentions to report the error, with senior pharmacists being more likely to report. Perceived behavioural control (ease or difficulty of reporting), Descriptive Norms (belief that other pharmacists would report) and Attitudes towards Behaviour (expected benefits of reporting) showed good correlation with, and were statistically significant predictors of, intention to report the error [R = 0.568, R(2) = 0.323, adjusted R(2) = 0.293, P < 0.001]. CONCLUSIONS: This study suggests that efforts to improve medication safety incident reporting by hospital pharmacists should focus on their behavioural and control beliefs about the reporting process. This should include instilling greater confidence about the benefits of reporting and not harming professional relationships with doctors, greater clarity about what/not to report and a simpler reporting system. PMID- 26142281 TI - Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages. AB - Mammalian development begins with the segregation of embryonic and extra embryonic lineages in the blastocyst. Recent studies revealed cell-to-cell gene expression heterogeneity and dynamic cell rearrangements during mouse blastocyst formation. Thus, mechanistic understanding of lineage specification requires quantitative description of gene expression dynamics at a single-cell resolution in living embryos. However, only a few fluorescent gene expression reporter mice are available and quantitative live image analysis is limited so far. Here, we carried out a fluorescence gene-trap screen and established reporter mice expressing Venus specifically in the first lineages. Lineage tracking, quantitative gene expression and cell position analyses allowed us to build a comprehensive lineage map of mouse pre-implantation development. Our systematic analysis revealed that, contrary to the available models, the timing and mechanism of lineage specification may be distinct between the trophectoderm and the inner cell mass. While expression of our trophectoderm-specific lineage marker is upregulated in outside cells upon asymmetric divisions at 8- and 16 cell stages, the inside-specific upregulation of the inner-cell-mass marker only becomes evident at the 64-cell stage. This study thus provides a framework toward systems-level understanding of embryogenesis marked by high dynamicity and stochastic variability. PMID- 26142283 TI - Effect of FliG three amino acids deletion in Vibrio polar-flagellar rotation and formation. AB - Most of bacteria can swim by rotating flagella bidirectionally. The C ring, located at the bottom of the flagellum and in the cytoplasmic space, consists of FliG, FliM and FliN, and has an important function in flagellar protein secretion, torque generation and rotational switch of the motor. FliG is the most important part of the C ring that interacts directly with a stator subunit. Here, we introduced a three-amino acids in-frame deletion mutation (DeltaPSA) into FliG from Vibrio alginolyticus, whose corresponding mutation in Salmonella confers a switch-locked phenotype, and examined its phenotype. We found that this FliG mutant could not produce flagellar filaments in a fliG null strain but the FliG(DeltaPSA) protein could localize at the cell pole as does the wild-type protein. Unexpectedly, when this mutant was expressed in a wild-type strain, cells formed flagella efficiently but the motor could not rotate. We propose that this different phenotype in Vibrio and Salmonella might be due to distinct interactions between FliG mutant and FliM in the C ring between the bacterial species. PMID- 26142284 TI - Receptor expression and responsiveness of human peripheral blood mononuclear cells to a human cytomegalovirus encoded CC chemokine. AB - Human cytomegalovirus is a ubiquitous pathogen that infects the majority of the world's population. After long period of time co-evolving with human being, this pathogen has developed several strategies to evade host immune surveillance. One of the major trick is encoding homologous to those of the host organism or stealing host cellular genes that have significant functions in immune system. To date, we have found several viral immune analogous which include G protein coupled receptor, class I major histocompatibility complex and chemokine. Chemokine is a small group of molecules which is defined by the presence of four cysteines in highly conserved region. The four kinds of chemokines (C, CC, CXC, and CX3C) are classified based on the arrangement of 1 or 2 N-terminal cysteine residues. UL128 protein is one of the analogous that encoded by human cytomegalovirus that has similar amino acid sequences to the human CC chemokine. It has been proved to be one of the essential particles that involved in human cytomegalovirus entry into epithelial/endothelial cells as well as macrophages. It is also the target of potent neutralizing antibodies in human cytomegalovirus seropositive individuals. We had demonstrated the chemotactic trait of UL128 protein in our previous study. Recombinant UL128 in vitro has the ability to attract monocytes to the infection region and enhances peripheral blood mononuclear cell proliferation by activating the MAPK/ERK signaling pathway. However, the way that this viral encoded chemokine interacting with peripheral blood mononuclear cells and the detailed mechanism that involving the virus entry into host cells keeps unknown. Here we performed in vitro investigation into the effects of UL128 protein on peripheral blood mononuclear cell's activation and receptor binding, which may help us further understand the immunomodulatory function of UL128 protein as well as human cytomegalovirus diffusion mechanism. PMID- 26142285 TI - The Pocket Psychiatrist: Tools to enhance psychiatry education in family medicine. AB - Primary care is the setting where the majority of patients seek assistance for their mental health problems. To assist family medicine residents in providing effective care to patients for mental health problems during residency and after graduation, it is essential they receive training in the assessment, diagnosis, and treatment of common mental health conditions. While there is some limited education time with a psychiatrist in our department, residents need tools and resources that provide education during their continuity clinics even when the psychiatrist is not available. Information on two tools that were developed is provided. These tools include teaching residents a brief method for conducting a psychiatric interview as well as a means to access evidence-based information on diagnosis and treatment of mental health conditions through templates available within our electronic medical record. PMID- 26142286 TI - Sailing smoothly across the cultural divide: Constructing effective behavioral science presentations for medical audiences. AB - Beginning behavioral science faculty, who are critical residency program contributors, face significant immediate challenges that often diminish their effectiveness and increase the time it takes to translate and reformat their expertise into relevant and meaningful educational presentations. Residency program culture and competency-based learning are quite different from the educational objectives and teaching environments found in most behavioral health training programs. The goal of this article is to provide beginning behavior science faculty, who are typically on their own and learning on the job, with a guide to the core educational perspectives and skills required as well as key resources that are available to them. Since a significant portion of behavioral science faculty's teaching time revolves around small and large group presentations, our guide focuses on how to incorporate key strategies and resources into relevant, evidenced-based and, most importantly, effective behavioral health presentations for the program's resident physicians. Specifically, our recommendations include selection of content, methods of content organization, techniques for actively engaging resident physicians in discussing the significance of the topics, and descriptions of numerous Internet resources for the primary mental health topics that concern family medicine trainees. Finally, it is emphasized that the relevant and effective use of these recommendations is dependent upon the behavioral science faculty educator's first understanding and appreciating how physicians' think, speak, and prioritize information while caring for their patients. PMID- 26142287 TI - Preparing family physicians for the care of patients with severe and persistent mental illness: Examples from two U.S. residency programs. AB - Individuals with severe and persistent mental illness have increased morbidity and mortality and significant barriers to accessing health care. Although primary care providers deliver most health care for this population, residency training programs generally lack specialized training in this area. This article describes the approaches of two family medicine residency programs in addressing this educational gap. Each program collaborated with external organizations to create service models that would enhance patient access, while immersing residents in the care of patients with severe and persistent mental illness. Residents educated in these programs gain experience with an underserved population, practice advanced skills in managing complex medical and psychiatric illness, and increase knowledge from collaborative work in unique care settings. Further implementation of programs like these, and rigorous study of such programs, could have significant benefits for family medicine education and the care of patients with severe and persistent mental illness. PMID- 26142288 TI - Behavioral health integration: Transforming patient care, medical resident education, and physician effectiveness. AB - Integrating behavioral health care into the family medicine residency has had a dramatic impact on patient care, resident training, and physician effectiveness. With a cursory glance, it may seem that integrated behavioral health providers spend their days exclusively having 30-min office visits with patients. A full exploration, however, reveals that well-integrated behavioral health offers not only brief and effective visits with patients but also increased collaboration, better patient comanagement, and multiple opportunities for resident learning. Behavioral health integration transforms the way in which medical providers at all levels of training work, teach, and conceptualize their future practice. In an internal survey of 33 medical providers in an integrated family medicine residency, 97% of respondents report they value behavioral health integration to such a degree that they are more likely to accept a job in a setting that offers integrated behavioral health. PMID- 26142289 TI - Training models for enhancing psychiatric care in primary care. PMID- 26142290 TI - Culturally responsive integrated health care: Key issues for medical education. AB - Primary care providers are increasingly responsible for providing mental health care in the United States. For those patients who do receive specialty mental health services, the primary care provider functions as the main entry point into the mental health system. Given the persistent racial and ethnic health disparities in the United States, it is not surprising that mental health disparities also present a difficult challenge for both the U.S. health system and for frontline practitioners. Physicians-in-training require tools for rapid psychiatric assessment that will quickly identify pertinent symptom clusters and distinguish between major psychological disorders. It is incumbent on residency faculty to teach resident physicians how to provide culturally responsive mental health assessment and intervention/referral knowledge and skills toward the elimination of these disparities and toward patient-centered care. This article begins with an overview of health disparities and barriers to health and mental health care access, followed by a discussion of culturally responsive care including an example of a culturally responsive educational program in the United States that is directly targeting the problem of access in that geographic region. It concludes with a review of educational strategies for enhancing culturally responsive behavioral and mental health care by physicians in training. PMID- 26142292 TI - From Subjective Cognitive Complaints to Dementia: Who is at Risk?: A Systematic Review. AB - Subjective cognitive complaints (SCCs) are frequent in the elderly population. The majority of individuals with subjective complaints never progress to significant cognitive decline, but some of them have a higher risk of progression to objective cognitive impairment than persons with no cognitive concerns. We performed a systematic review of community-based studies that focused on the progression risk associated with SCC and on the complainers' characteristics associated with progression. Seventeen studies were included. As a group, SCCs are associated with a significantly higher risk of progression to dementia. Worried complainers, persons who refer an impact of their complaints on activities of daily living, and those whose complaints are also noticed by an informant have the highest risk of progression. Taking into account the fluctuating course of SCC and their frequent reversion, care should be taken to not overvaluate them. Further studies are necessary to better define risk features. PMID- 26142293 TI - Promote the Health of Dementia Caregivers. AB - Caregivers of people with Alzheimer's dementia (AD) will become increasingly important as governments across the world cut health care funding. The vast majority of the care for people with AD is and will be carried out by informal caregivers, in other words, their spouses, children, and friends, people who typically have no training in this task and, certainly in the early days after diagnosis, little knowledge of what the person with AD is going through or what the future holds. The fact that people with AD face progressive cognitive and functional decline and that widespread individual differences are the norm rather than the exception makes it difficult to predict how quickly/slowly they will deteriorate. Caregiver-centered training and individual guidance based on the specific situation for informal dementia caregivers is going to become an international priority. We will need to care not only for the patient but also for their caregivers. PMID- 26142291 TI - All the way from the cortex: a review of auditory corticosubcollicular pathways. AB - Enrico Mugnaini has devoted part of his long and fruitful neuroscientific career to investigating the structural similarities between the cerebellar cortex and one of the first relay stations of the mammalian auditory pathway: the dorsal cochlear nucleus. The hypothesis of the cerebellar-like nature of the superficial layers of the dorsal cochlear nucleus received definitive support with the discovery and extensive characterization in his laboratory of unipolar brush cells, a neuron type unique to certain regions of the cerebellar cortex and to the granule cell domains of the cochlear nuclei. Paradoxically, a different line of research carried out in his laboratory revealed that, unlike the mammalian cerebellar cortex, the dorsal cochlear nucleus receives direct projections from the cerebral cortex, a fact that constitutes one of the main differences between the cerebellum and the dorsal cochlear nucleus. In an article published in 1995, Mugnaini's group described in detail the novel direct projections from the rat auditory neocortex to various subcollicular auditory centers, including the nucleus sagulum, the paralemniscal regions, the superior olivary complex, and the cochlear nuclei (Feliciano et al., Auditory Neuroscience 1995; 1:287-308). This review gives Enrico Mugnaini credit for his seminal contribution to the knowledge of auditory corticosubcollicular projections and summarizes how this growing field has evolved in the last 20 years. PMID- 26142294 TI - Reply to the Editor--Altered in vivo systolic function in the short QT syndrome anticipated in silico. PMID- 26142295 TI - Preventing cardiac implantable electronic device infections. AB - Cardiac implantable electronic devices (CIEDs) have dramatically improved clinical outcomes in patients with heart disease, and the number of CIED-related procedures being performed continues to grow. Unfortunately, the rate of device related infection (DRI) is increasing disproportionately to the rate of implantation, with DRI rates of >2% in many series. This increase in DRI is a consequence of the increased number of patients with a higher burden of comorbidities, who are more susceptible to infection and are undergoing more complex device procedures. Identification of high-risk patients is an important component of procedural planning, and targeted therapy and surveillance may be beneficial in certain groups. An understanding of the pathophysiology of DRI has facilitated more effective and widespread use of prophylactic antibiotics; however, current guidelines for antibiotic prophylaxis are based on a relatively small evidence base. Clinical equipoise remains regarding the optimal prophylactic regimen, and we are continuing to learn how best to manage these patients. In this review, we discuss the epidemiology and pathophysiology of DRI and its clinical presentation, the risk factors for DRI, and the existing and emerging evidence supporting strategies to prevent DRI. PMID- 26142296 TI - To the Editor--Altered in vivo systolic function in the short QT syndrome anticipated in silico. PMID- 26142297 TI - Metabolic syndrome, atrial fibrillation, and stroke: Tackling an emerging epidemic. AB - The prevalence of atrial fibrillation (AF) and AF-related stroke is set to increase dramatically in coming decades, with developing regions such as Latin America experiencing the greatest impact. These trends are primarily driven by aging populations and by the increasing prevalence of the metabolic syndrome. The metabolic syndrome describes an association between diabetes, hypertension, obesity, and dyslipidemia and an increased risk of cardiovascular disease. It is in large part the result of unbalanced diet and sedentary lifestyle. These essentially modifiable risk factors are becoming more prevalent with the widespread adoption of so-called Western lifestyles. This review examines the physiology underlying the link between the metabolic syndrome and AF. Next, it highlights the importance of addressing lifestyle-related risk factors to mitigate the trend toward increasing AF prevalence. It then goes on to discuss the importance of stroke prevention therapy in patients with established AF, focusing on the relative merits of various available options for anticoagulation. Given the recent availability of comprehensive data on the 4 currently available non-vitamin K antagonist oral anticoagulant drugs, this review concludes by discussing the relative merits of specific agents in individual patient groups. PMID- 26142298 TI - Diagnostic value of T-wave morphology changes during "QT stretching" in patients with long QT syndrome. AB - BACKGROUND: Specific T-wave patterns on the resting electrocardiogram (ECG) aid in diagnosing long QT syndrome (LQTS) and identifying the specific genotype. However, provocation tests often are required to establish a diagnosis when the QT interval is borderline at rest. OBJECTIVE: The purpose of this study was to determine whether T-wave morphology changes provoked by standing aid in the diagnosis of LQTS and determination of the genotype. METHODS: The quick-standing test was performed by 100 LQTS patients (40 type 1 [LQT1], 42 type 2 [LQT2], 18 type 3 [LQT3]) and 100 controls. Logistic regression was used to determine whether T-wave morphology changes provoked by standing added to the already established diagnostic value of QTc stretching in identifying LQTS. RESULTS: During maximal QT stretching, the T-wave morphologies that best discriminated LQTS from controls included "notched," "late-onset," and "biphasic" T waves. These 3 categories were grouped into a category named "abnormal T-wave response to standing." During quick standing, a QTc stretched >=490 ms increased the odds of correctly identifying LQTS. T-wave morphology changes provoked by standing were most helpful for identifying LQT2, less helpful for LQT1, and least helpful for LQT3. CONCLUSION: The sudden heart rate acceleration produced by abrupt standing not only increases the QTc but also exposes abnormal T waves that are valuable for diagnosing LQTS. PMID- 26142299 TI - Further insights into blood pressure induced premature beats: Transient depolarizations are associated with fast myocardial deformation upon pressure decline. AB - BACKGROUND: An acute increase in blood pressure is associated with the occurrence of premature ventricular complexes (PVCs). OBJECTIVE: We aimed to study the timing of these PVCs with respect to afterload-induced changes in myocardial deformation in a controlled, preclinically relevant, novel closed-chest pig model. METHODS: An acute left ventricular (LV) afterload challenge was induced by partial balloon inflation in the descending aorta, lasting 5-10 heartbeats (8 pigs; 396 inflations). RESULTS: Balloon inflation enhanced the reflected wave (augmentation index 30% +/- 8% vs 59% +/- 6%; P < .001), increasing systolic central blood pressure by 35% +/- 4%. This challenge resulted in a more abrupt LV pressure decline, which was delayed beyond ventricular repolarization (rate of pressure decline 0.16 +/- 0.01 mm Hg/s vs 0.27 +/- 0.04 mm Hg/ms; P < .001 and interval T-wave to peak pressure 1 +/- 12 ms vs 36 +/- 9 ms; P = .008), during which the velocity of myocardial shortening at the basal septum increased abruptly (ie, postsystolic shortening) (peak strain rate -0.6 +/- 0.5 s(-1) vs 2.5 +/- 0.8 s(-1); P < .001). It is exactly at this time of LV pressure decline, with increased postsystolic shortening, and not at peak pressure, that PVCs occur (22% of inflations). These PVCs preferentially occurred at the basal and apical segments. In the same regions, monophasic action potentials demonstrated the appearance of delayed afterdepolarization-like transient depolarizations as origin of PVCs. CONCLUSION: An acute blood pressure increase results in a more abrupt LV pressure decline, which is delayed after ventricular repolarization. This has a profound effect on myocardial mechanics with enhanced postsystolic shortening. Coincidence with induced transient depolarizations and PVCs provides support for the mechanoelectrical origin of pressure-induced premature beats. PMID- 26142301 TI - A novel method to predict the proportional risk of sudden cardiac death in heart failure: Derivation of the Seattle Proportional Risk Model. AB - BACKGROUND: Patients with heart failure are at increased risk of both sudden death and pump failure death. Strategies to better identify those who have greatest net benefit from implantable cardioverter-defibrillator (ICD) implantation could reduce morbidity and maximize cost-effectiveness of ICDs. OBJECTIVE: We aimed to identify baseline variables in patients with cardiomyopathy that are independently associated with a disproportionate fraction of mortality risk attributable to sudden death vs nonsudden death. METHODS: We used data from 9885 patients with heart failure without ICDs, of whom 2552 died during an average follow-up of 2.3 years. Using commonly available baseline clinical and demographic variables, we developed a multivariate regression model to identify variables associated with a disproportionate risk of sudden death. RESULTS: We confirmed that lower ejection fraction and better functional class were associated with a greater proportion of mortality due to sudden death. Younger age, male sex, and higher body mass index were independently associated with a greater proportional risk of sudden death, while diabetes mellitus, hyper/hypotension, higher creatinine level, and hyponatremia were associated with a disproportionately lower risk of sudden death. The use of several heart failure medications, left ventricular end-diastolic dimension, or NT-pro brain natriuretic peptide concentrations were not associated with a disproportionate risk of sudden death. CONCLUSION: Several easily obtained baseline demographic and clinical variables, beyond ejection fraction and New York Heart Association functional class, are independently associated with a disproportionately increased risk of sudden death. Further investigation is needed to assess whether this novel predictive method can be used to target the use of lifesaving therapies to populations who will derive greatest mortality benefit . PMID- 26142300 TI - Association between ventricular pacing and persistent atrial fibrillation in patients indicated to elective pacemaker replacement: Results of the Prefer for Elective Replacement MVP (PreFER MVP) randomized study. AB - BACKGROUND: Pacing in the right ventricle can cause a variety of detrimental effects, including atrial tachyarrhythmias (atrial tachycardia [AT]/atrial fibrillation [AF]). OBJECTIVE: The purpose of this study was to evaluate the incidence and predictors of persistent AT/AF in patients with long-term exposure to ventricular pacing. METHODS: In a multicenter international trial, 605 patients (age 75 +/- 11 years, 240 women) referred for replacement of an implanted pacemaker or implantable cardioverter-defibrillator (ICD), with a history of high-percentage (>40%) ventricular pacing, were randomly allocated to standard dual-chamber pacing or managed ventricular pacing (MVP), a pacing modality that minimizes ventricular pacing. The main end-point of this secondary analysis of the PreFER MVP randomized study was persistent AT/AF, defined as >=7 consecutive days with AT/AF or AT/AF interrupted by atrial cardioversion or AT/AF present during 2 consecutive follow-up visits. RESULTS: Persistent AT/AF was observed in 71 patients (11.7%) after 2 years of follow-up. At multivariable Cox regression analysis, prior AT/AF (hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.20-6.22, P = .017) and ventricular pacing percentage, estimated in the first 3 months, >=10% (HR 3.24, 95% 95% CI 1.13-9.31, P = .029) were independent predictors for persistent AT/AF. MVP was associated with persistent AT/AF risk (HR 3.41, 95% 95% CI 1.10-10.6, P = .024) in the subgroup of patients with baseline long PR interval (PR >230 ms) but not in the whole population. CONCLUSION: In pacemaker and ICD replacement patients, a high percentage of ventricular pacing is associated with higher risk of persistent AT/AF. Use of algorithms that minimize right ventricular pacing may benefit patients with normal spontaneous AV conduction but should be evaluated with caution in patients with long PR interval. PMID- 26142302 TI - Electrophysiologic consequences of KATP gain of function in the heart: Conduction abnormalities in Cantu syndrome. AB - BACKGROUND: Gain-of-function (GOF) mutations in the KATP channel subunits Kir6.1 and SUR2 cause Cantu syndrome (CS), a disease characterized by multiple cardiovascular abnormalities. OBJECTIVE: The purpose of this study was to better determine the electrophysiologic consequences of such GOF mutations in the heart. METHODS: We generated transgenic mice (Kir6.1-GOF) expressing ATP-insensitive Kir6.1[G343D] subunits under alpha-myosin heavy chain (alpha-MHC) promoter control, to target gene expression specifically in cardiomyocytes, and performed patch-clamp experiments on isolated ventricular myocytes and invasive electrophysiology on anesthetized mice. RESULTS: In Kir6.1-GOF ventricular myocytes, KATP channels showed decreased ATP sensitivity but no significant change in current density. Ambulatory ECG recordings on Kir6.1-GOF mice revealed AV nodal conduction abnormalities and junctional rhythm. Invasive electrophysiologic analyses revealed slowing of conduction and conduction failure through the AV node but no increase in susceptibility to atrial or ventricular ectopic activity. Surface ECGs recorded from CS patients also demonstrated first degree AV block and fascicular block. CONCLUSION: The primary electrophysiologic consequence of cardiac KATP GOF is on the conduction system, particularly the AV node, resulting in conduction abnormalities in CS patients who carry KATP GOF mutations. PMID- 26142303 TI - Comparison of subgroups of breast cancer patients on pain and co-occurring symptoms following chemotherapy. AB - PURPOSE: The purposes of this study, in a sample of women with breast cancer receiving chemotherapy (CTX), were to identify subgroups of women with distinct experiences with the symptom cluster of pain, fatigue, sleep disturbance, and depressive symptoms and evaluate differences in demographic and clinical characteristics, differences in psychological symptoms, and differences in pain characteristics among these subgroups. METHODS: Patients completed symptom questionnaires in the week following CTX administration. Latent class profile analysis (LCPA) was used to determine the patient subgroups. RESULTS: Three subgroups were identified: 140 patients (35.8 %) in the "low," 189 patients (48.3 %) in the "moderate," and 62 patients (15.9 %) in the "all high" latent class. Patients in the all high class had a lower functional status, a higher comorbidity profile, a higher symptom burden, and a poorer quality of life. CONCLUSIONS: Study findings provide evidence of the utility of LCPA to explain inter-individual variability in the symptom experience of patients undergoing CTX. The ability to characterize subgroups of patients with distinct symptom experiences allows for the identification of high-risk patients and may guide the design of targeted interventions that are tailored to an individual's symptom profile. PMID- 26142304 TI - Defining the Content of an Online Sexual Health Intervention: The MenSS Website. AB - BACKGROUND: Health promotion and risk reduction are essential components of sexual health care. However, it can be difficult to prioritize these within busy clinical services. Digital interventions may provide a new method for supporting these. OBJECTIVE: The MenSS (Men's Safer Sex) website is an interactive digital intervention developed by a multidisciplinary team, which aims to improve condom use in men who have sex with women (MSW). This paper describes the content of this intervention, and the rationale for it. METHODS: Content was informed by a literature review regarding men's barriers to condom use, workshops with experts in sexual health and technology (N=16) and interviews with men in sexual health clinics (N=20). Data from these sources were analyzed thematically, and synthesized using the Behavior Change Wheel framework. RESULTS: The MenSS intervention is a website optimized for delivery via tablet computer within a clinic waiting room setting. Key targets identified were condom use skills, beliefs about pleasure and knowledge about risk. Content was developed using behavior change techniques, and interactive website features provided feedback tailored for individual users. CONCLUSIONS: This paper provides a detailed description of an evidence-based interactive digital intervention for sexual health, including how behavior change techniques were translated into practice within the design of the MenSS website. Triangulation between a targeted literature review, expert workshops, and interviews with men ensured that a range of potential influences on condom use were captured. PMID- 26142305 TI - Impact of round-the-clock CSF Gram stain on empirical therapy for suspected central nervous system infections. AB - The impact of round-the-clock cerebrospinal fluid (CSF) Gram stain on overnight empirical therapy for suspected central nervous system (CNS) infections was investigated. All consecutive overnight CSF Gram stains between 2006 and 2011 were included. The impact of a positive or a negative test on empirical therapy was evaluated and compared to other clinical and biological indications based on institutional guidelines. Bacterial CNS infection was documented in 51/241 suspected cases. Overnight CSF Gram stain was positive in 24/51. Upon validation, there were two false-positive and one false-negative results. The sensitivity and specificity were 41 and 99 %, respectively. All patients but one had other indications for empirical therapy than Gram stain alone. Upon obtaining the Gram result, empirical therapy was modified in 7/24, including the addition of an appropriate agent (1), addition of unnecessary agents (3) and simplification of unnecessary combination therapy (3/11). Among 74 cases with a negative CSF Gram stain and without formal indication for empirical therapy, antibiotics were withheld in only 29. Round-the-clock CSF Gram stain had a low impact on overnight empirical therapy for suspected CNS infections and was associated with several misinterpretation errors. Clinicians showed little confidence in CSF direct examination for simplifying or withholding therapy before definite microbiological results. PMID- 26142314 TI - Region and dynamic specificities of adult neural stem cells and oligodendrocyte precursors in myelin regeneration in the mouse brain. AB - Myelin regeneration can occur in the brain following demyelination. Parenchymal oligodendrocyte progenitors (pOPC) are known to play a crucial role in this process. Neural stem cells (NSC) residing in the ventricular-subventricular zone (V-SVZ) also have the ability to generate oligodendrocytes but their contribution to endogenous myelin repair was so far considered to be negligible. Here, we addressed the relative contribution of pOPC and V-SVZ-derived neural progenitors (SVZdNP) to remyelination in cuprizone mouse models of acute or chronic corpus callosum (CC) demyelination. Using genetic tracing, we uncover an unexpected massive and precocious recruitment of SVZdNP in the anterior CC after acute demyelination. These cells very quickly adopt an oligodendrocytic fate and robustly generate myelinating cells as efficiently as pOPC do. In more posterior areas of the CC, SVZdNP recruitment is less important whereas pOPC contribute more, underlining a regionalization in the mobilization of these two cell populations. Strikingly, in a chronic model when demyelination insult is sustained in time, SVZdNP minimally contribute to myelin repair, a failure associated with a depletion of NSC and a drastic drop of progenitor cell proliferation in V-SVZ. In this context, pOPC remain reactive, and become the main contributors to myelin regeneration. Altogether our results highlight a region and context-dependent contribution of SVZdNP to myelin repair that can equal pOPC. They also raise the question of a possible exhaustion of V-SVZ proliferation potential in chronic pathologies. PMID- 26142315 TI - Tubedown regulation of retinal endothelial permeability signaling pathways. AB - Tubedown (Tbdn; Naa15), a subunit of the N-terminal acetyltransferase NatA, complexes with the c-Src substrate Cortactin and supports adult retinal homeostasis through regulation of vascular permeability. Here we investigate the role of Tbdn expression on signaling components of retinal endothelial permeability to understand how Tbdn regulates the vasculature and supports retinal homeostasis. Tbdn knockdown-induced hyperpermeability to Albumin in retinal endothelial cells was associated with an increase in the levels of activation of the Src family kinases (SFK) c-Src, Fyn and Lyn and phospho Cortactin (Tyr421). The knockdown of Cortactin expression reduced Tbdn knockdown induced permeability to Albumin and the levels of activated SFK. Inhibition of SFK in retinal endothelial cells decreased Tbdn knockdown-induced permeability to Albumin and phospho-Cortactin (Tyr421) levels. Retinal lesions of endothelial specific Tbdn knockdown mice, with tissue thickening, fibrovascular growth, and hyperpermeable vessels displayed an increase in the levels of activated c-Src. Moreover, the retinal lesions of patients with proliferative diabetic retinopathy (PDR) associated with a loss of Tbdn expression and hyperpermeability to Albumin displayed increased levels of activated SFK in retinal blood vessels. Taken together, these results implicate Tbdn as an important regulator of retinal endothelial permeability and homeostasis by modulating a signaling pathway involving c-Src and Cortactin. PMID- 26142316 TI - Silibinin down-regulates FAT10 and modulate TNF-alpha/IFN-gamma-induced chromosomal instability and apoptosis sensitivity. AB - Pleiotropic pro-inflammatory cytokines, TNF-alpha and IFN-gamma (TI), play important yet diverse roles in cell survival, proliferation, and death. Recent evidence highlights FAT10 as a downstream molecule in the pathway of inflammation induced tumorigenesis through mediating the effect of cytokines in causing numerical CIN and protecting cells from cytokines-induced cell death. cDNA microarray analysis of cells treated with TI revealed 493 deregulated genes with FAT10 being the most up-regulated (85.7-fold) gene and NF-kappaB being the key nodal hub of TI-response genes. Silibinin is reported to be a powerful antioxidant and has anti-C effects against various carcinomas by affecting various signaling molecules/pathways including MAPK, NF-kappaB and STATs. As NF kappaB signaling pathway is a major mediator of the tumor-promoting activities of TI, we thus examine the effects of silibinin on TI-induced FAT10 expression and CIN. Our data showed that silibinin inhibited expression of FAT10, TI-induced chromosome instability (CIN) as well as sensitizes cells to TI-induced apoptosis. Significantly, silibinin suppressed intra-tumorally injected TNF-alpha-induced tumor growth. This represents the first report associating silibinin with FAT10 and demonstrating that silibinin can modulate TI-induced CIN, apoptosis sensitivity and suppressing TNF-alpha-induced tumor growth. PMID- 26142317 TI - Discovery of novel N-(5-(tert-butyl)isoxazol-3-yl)-N'-phenylurea analogs as potent FLT3 inhibitors and evaluation of their activity against acute myeloid leukemia in vitro and in vivo. AB - FLT3 inhibitors have been explored as a viable therapy for acute myeloid leukemia (AML). However, the clinical outcomes of these FLT3 inhibitors were underwhelming except AC220. Therefore, the development of novel FLT3 inhibitors with high potency against both FLT3-WT and FLT3-ITD mutants are strongly demanded at the present time. In this study, we designed and synthesized a series of novel N-(5 (tert-butyl)isoxazol-3-yl)-N'-phenylurea derivatives as FLT3 inhibitors. SAR studies focused on the fused rings led to the discovery of a series of compounds with high potency against FLT3-ITD-bearing MV4-11 cells and significantly inhibitory activity toward FLT3. Among these compounds, N-(5-(tert-butyl)isoxazol 3-yl)-N'-(4-(7-methoxyimidazo[1,2-a]pyridin-2-yl)phenyl)urea (16i), displayed acceptable aqueous solubility, desirable pharmacokinetic profile and high cytotoxicity selectivity against MV4-11 cells. This compound can inhibit phosphorylation of FLT3 and induce apoptosis in a concentration-dependent manner. Further in vivo antitumor studies showed that 16i led to complete tumor regression in the MV4-11 xenograft model at a dose of 60 mg/kg/d while without observable body weight loss. This study had provided us a new chemotype of FLT3 inhibitors as novel therapic candidates for AML. PMID- 26142318 TI - The twin drug approach for novel nicotinic acetylcholine receptor ligands. AB - The association of two pharmacophoric entities generates so-called 'twin drugs' or dimer derivatives. We applied this approach for the design of a small compound library for the interaction with alpha4beta2(*) nicotinic acetylcholine receptors (nAChRs). In this compound series, the nAChR ligand N,N-dimethyl-2-(pyridin-3 yloxy)ethan-1-amine 9 served as one pharmacological entity and it was initially kept constant as one part of the 'twin' compound. 'Twin' compounds with identical or non-identical entities using the 'no linker mode' or 'overlap' mode were synthesized and evaluated for their nAChR affinities. Compound 17a showed the highest affinity for the alpha4beta2(*) nAChR subtype (Ki=0.188 nM) and its (di)fluoro analogs could retain nanomolar affinities, when replacing pyridine as the hydrogen bond acceptor system by mono- or difluoro-phenyls. The 'twin drug' approach proved to provide compounds with high affinity and subtype selectivity for alpha4beta2(*) nAChRs. PMID- 26142319 TI - One-pot synthesis of human metabolites of SAR548304 by fungal peroxygenases. AB - Unspecific peroxygenases (UPOs, EC 1.11.2.1) have proved to be stable oxygen transferring biocatalysts for H2O2-dependent transformation of pharmaceuticals. We have applied UPOs in a drug development program and consider the enzymatic approach in parallel to a conventional chemical synthesis of the human metabolites of the bile acid reabsorption inhibitor SAR548304. Chemical preparation of N,N-di-desmethyl metabolite was realized by a seven-step synthesis starting from a late precursor of SAR548304 and included among others palladium catalysis and laborious chromatographic purification with an overall yield of 27%. The enzymatic approach revealed that the UPO of Marasmius rotula is particularly suitable for selective N-dealkylation of the drug and enabled us to prepare both human metabolites via one-pot conversion with an overall yield of 66% N,N-di-desmethyl metabolite and 49% of N-mono-desmethylated compound in two separated kinetic-controlled reactions. PMID- 26142320 TI - Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid. AB - INTRODUCTION: Clinical practice guidelines are of increasing importance in the decision making for the treatment of knee osteoarthritis. Inconsistent recommendations regarding the use of intra-articular hyaluronic acid for the treatment of knee osteoarthritis have led to confusion among treating physicians. METHODS: Literature search to identify clinical practice guidelines that provide recommendations regarding the use of intra-articular hyaluronic acid treatment for knee osteoarthritis was conducted. Included guidelines were appraised using the AGREE II instrument. Guideline development methodologies, how the results were assessed, the recommendation formation, and work group composition were summarized. RESULTS: Overall, 10 clinical practice guidelines were identified that met our inclusion criteria. AGREE II domain scores were variable across the included guidelines. The methodology utilized across the guidelines was heterogeneous regarding the evidence inclusion criteria, analysis of evidence results, formulation of clinical practice recommendations, and work group composition. The recommendations provided by the guidelines for intra-articular hyaluronic acid treatment for knee osteoarthritis are highly inconsistent as a result of the variability in guideline methodology. Overall, 30% of the included guidelines recommended against the use of intra-articular hyaluronic acid in the treatment of knee osteoarthritis, while 30% deemed the treatment an appropriate intervention under certain scenarios. The remaining 40% of the guidelines provided either an uncertain recommendation or no recommendation at all, based on the high variability in reviewed evidence regarding efficacy and trial quality. CONCLUSION: There is a need for a standard "appropriate methodology" that is agreed upon for osteoarthritis clinical practice guidelines in order to prevent the development of conflicting recommendations for intra-articular hyaluronic acid treatment for knee osteoarthritis, and to assure that treating physicians who are utilizing these guidelines are making their clinical decisions on the best available evidence. At present, the inconsistent recommendations provided for intra-articular hyaluronic acid treatment make it difficult for clinical professionals to determine its appropriateness when treating patients with knee osteoarthritis. PMID- 26142321 TI - Plain radiography or magnetic resonance imaging (MRI): Which is better in assessing outcome in clinical trials of disease-modifying osteoarthritis drugs? Summary of a debate held at the World Congress of Osteoarthritis 2014. AB - Osteoarthritis (OA) is the most common disease of synovial joints and currently lacks treatment options that modify structural pathology. Imaging is ideally suited for directly evaluating efficacy of disease-modifying OA drugs (DMOADs) in clinical trials, with plain radiography and MRI being most often applied. The current article is based on a debate held on April 26, 2014, at the World Congress of Osteoarthritis: The authors were invited to contrast strengths and limitations of both methods, highlighting scientific evidence on reliability, construct-validity, and correlations with clinical outcome, and comparing their sensitivity to change in knee OA and sensitivity to DMOAD treatment. The authors concluded that MRI provides more comprehensive information on articular tissues pathology, and that implementation of radiography in clinical trials remains a challenge. However, neither technique has thus far been demonstrated to be strongly superior over the other; for the time being it therefore appears advisable to use both in parallel in clinical trials, to provide more evidence on their relative performance. Radiographic JSW strongly depends on adequate positioning; it is not specific to cartilage loss but also to the meniscus. MRI provides somewhat superior sensitivity to change compared with the commonly used non-fluoroscopic radiographic acquisition protocols, and has recently provided non-location-dependent measures of cartilage thickness loss and gain, which are potentially more sensitive in detecting DMOAD effects than radiographic JSW or region-specific MRI. Non-location-dependent measures of cartilage thickness change should thus be explored further in context of anabolic and anti-catabolic DMOADs. PMID- 26142322 TI - Impact of epigenetic mechanisms on therapeutic approaches of hemoglobinopathies. AB - Hemoglobinopathies are inherited disorders characterized by anomalies of structure, function or production of globin chains. From conception to adulthood, the different expressions over time of the various globin chains depend on the activation/deactivation of different globin genes through methylation and chromatin remodeling processes. The most significant clinical disorders are beta thalassemia and sickle cell disease. The clinical management of these disorders engages regular blood transfusions. Another therapy is represented by allogeneic hematopoietic cells transplantation. There are several studies based on the innovative therapeutic strategies that involve some epigenetic mechanisms focused on the reactivation of gamma-globin gene expression. The induction of fetal hemoglobin expression in adulthood is an effective therapy for these disorders. Particularly interesting are the recent data on miRNAs showing the interaction of these molecules with different transcription factors such as MYB, KLF, BCL11A and SOX6. The aim of this review was to report an update on the dynamic epigenetic modifications as targets for therapy in hemoglobinopathies. PMID- 26142323 TI - Exome sequencing for molecular characterization of non-HFE hereditary hemochromatosis. AB - Diagnostic genetic testing for hereditary hemochromatosis is readily available for clinically relevant HFE variants (i.e., those that generate the C282Y, H63D and S65C HFE polymorphisms); however, genetic testing for other known causes of iron overload, including mutations affecting genes encoding hemojuvelin, transferrin receptor 2, HAMP, and ferroportin is not. As an alternative to conventional genetic testing we propose diagnostic use of whole exome sequencing for characterization of non-HFE hemochromatosis. To illustrate the effectiveness of whole exome sequencing as a diagnostic tool, we present the case of an 18-year old female with a probable case of juvenile hemochromatosis, who was referred for specialty care after testing negative for commonly occurring HFE variants. Whole exome sequencing offered complete coverage of target genes and is a fast, cost effective diagnostic tool for characterization of non-HFE hemochromatosis. PMID- 26142324 TI - Alpha hemoglobin stabilizing protein: Its causal relationship with the severity of beta thalassemia. AB - Thalassemia major is characterized by anemia, iron overload and cellular damage. The severity of symptoms correlates with the alpha/non-alpha globin imbalance and is proportional to the magnitude of alpha chain excess. Alpha hemoglobin stabilizing protein (AHSP), the erythroid specific alpha globin chaperone, stabilizes free alpha chains, and prevents the formation of reactive oxygen radicals. Though AHSP expression has been linked to the severity of beta thalassemia, its role as a probable genetic modifier of disease severity, has still not been unequivocally established. In the present study, the level of the chaperone has been seen to vary in regularly transfused beta thalassemia patients, being underexpressed in 64% of cases, upregulated in 16% and comparable to controls in 20% of the cases. This discrepancy may be attributed to the degree of DNA damage, % HbF, and the number of nucleated RBCs in the peripheral blood of these patients. Results reveal that a decrease in the free alpha chain pool, and hence the repertoire of unbound iron, due to elevated HbF and/or the presence of nucleated RBCs in the peripheral blood results in the upregulation of the AHSP gene. PMID- 26142325 TI - Hemoglobin level and morbidity in non-transfusion-dependent thalassemia. PMID- 26142326 TI - Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells. AB - Iron overload coupled with low hepcidin levels are characteristics of hereditary haemochromatosis. To understand the role of transferrin receptor (TFR) and intracellular iron in hepcidin secretion, Chinese hamster ovary transferrin receptor variant (CHO TRVb-1) cells were used that express iron-response-element depleted human TFRC mRNA (TFRC?IRE). Results showed that CHO TRVb-1 cells expressed higher basal levels of cell-surface TFR1 than HepG2 cells (2.2-fold; p < 0.01) and following 5 g/L holotransferrin treatment maintained constitutive over-expression at 24h and 48 h, contrasting the HepG2 cells where the receptor levels significantly declined. Despite this, the intracellular iron content was neither higher than HepG2 cells nor increased over time under basal or holotransferrin-treated conditions. Interestingly, hepcidin secretion in CHO TRVb 1 cells exceeded basal levels at all time-points (p < 0.02) and matched levels in HepG2 cells following treatment. While TFRC mRNA expression showed expected elevation (2h, p < 0.03; 4h; p < 0.05), slc40a1 mRNA expression was also elevated (2 h, p < 0.05; 4 h, p < 0.03), unlike the HepG2 cells. In conclusion, the CHO TRVb-1 cells prevented cellular iron-overload by elevating slc40a1 expression, thereby highlighting its significance in the absence of iron-regulated TFRC mRNA. Furthermore, hepcidin response to holotransferrin treatment was similar to HepG2 cells and resembled the human physiological response. PMID- 26142327 TI - Tyrosine kinase inhibitors: New class of antimalarials on the horizon? AB - Development of the antimalarial drug resistant strains has currently become a major public health challenge. There is an urgent need to develop new antimalarial drugs. Tyrosine kinase inhibitors (TKIs) are receiving increasing attention as anticancer therapy. It has revolutionarised the management of CML to say the least. TKIs are also increasingly being implicated in complicated but vital life cycle of malaria parasite. Hence we tested two commonly used but different classes of TKIs (imatinib and sorafenib) in-vitro for their antimalarial activity and possible synergistic activity with existing antimalarial drug. Antimalarial activity was tested with the help of modified WHO microtest technique in-vitro for five different Plasmodium falciparum laboratory strains (3D7, Dd2, 7G8, MRC2, PKL9). Imatinib and sorafenib showed a promising antimalarial activity with all the strains. These compounds caused dose dependent inhibition of parasite maturation. The isobologram analysis of the interactions of these TKIs with standard antimalarial drug, artesunate revealed distinct patterns of synergism, additivity and antagonism at different ratios. Imatinib showed worthwhile synergism with artesunate indicating imatinib and other tyrosine kinase inhibitors may have significant antimalarial activity and can be used in combination therapy. PMID- 26142328 TI - Mechanism of interferon-gamma production by monocytes stimulated with myeloperoxidase and neutrophil extracellular traps. AB - Neutrophil extracellular traps (NETs) have an important role in antimicrobial innate immunity and release substances that may modulate the immune response. We investigated the effects of soluble factors from NETs and neutrophil granule proteins on human monocyte function by using the Transwell system to prevent cell cell contact. NET formation was induced by exposing human neutrophils to phorbol myristate acetate (PMA). When monocytes were incubated with PMA alone, expression of interleukin (IL)-4, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha mRNA was upregulated, but IL-10, IL-12, and interferon (IFN)-gamma mRNA were not detected. Incubation of monocytes with NETs enhanced the expression of IL-10 and IFN-gamma mRNA, but not IL-12 mRNA. Myeloperoxidase stimulated IFN-gamma production by monocytes in a dose-dependent manner. Both a nuclear factor-kappaB inhibitor (PDTC) and an intracellular calcium antagonist (TMB-8) prevented upregulation of IFN-gamma production. Neither a combined p38alpha and p38beta inhibitor (SB203580) nor an extracellular signal-regulated kinase inhibitor (PD98059) suppressed IFN-gamma production. Interestingly, a combined p38gamma and p38delta inhibitor (BIRB796) significantly decreased IFN-gamma production. These findings suggest that myeloperoxidase induces IFN-gamma production by monocytes via p38gamma/delta mitogen-activated protein kinase. PMID- 26142329 TI - Proinflammatory and proosteoclastogenic potential of peripheral blood mononuclear cells from Gaucher patients: Implication for bone pathology. AB - Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells of monocyte/macrophage system. Bone compromise in Gaucher disease patients is the most disabling aspect of the disease. However, pathophysiological aspects of skeletal alterations are still poorly understood. On the other hand it is well known that inflammation is a key player in GD pathology. In this work, we revealed increased levels of the proinflammatory CD14(+)CD16(+) monocyte subset and increased inflammatory cytokine production by monocytes and T cells in the circulation of GD patients. We showed increased levels of osteoclast precursors in PBMC from patients and a higher expression of RANKL in the surface of T cells. PBMC from patients presented higher osteoclast differentiation compared to healthy controls when cultured in the presence of M-CSF alone or in combination with RANKL. In vitro treatment with Velaglucerase reduced osteoclast levels to control levels. On the other hand THP-1 derived osteoclast precursors cultured in the presence of conditioned media from PBMC of GD patients presented higher differentiation to active osteoclasts. This induction involved TNF-alpha and RANKL. PMID- 26142330 TI - Growth differentiation factor-15 in children and adolescents with thalassemia intermedia: Relation to subclinical atherosclerosis and pulmonary vasculopathy. AB - BACKGROUND: Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Growth differentiation factor-15 (GDF 15), a member of the transforming growth factor-beta superfamily, is a marker of ineffective erythropoiesis in several anemias. AIM: To determine GDF-15 levels in children and adolescents with TI and the relation to hemolysis, iron overload and cardiovascular complications. METHODS: GDF-15 was measured in 35 TI patients without symptoms for heart disease and correlated to echocardiographic parameters and carotid intima media thickness (CIMT). RESULTS: GDF-15 levels were significantly higher in TI patients compared with controls (p < 0.001). Transfusion dependent patients had higher GDF-15 than non-transfusion dependent patients. TI patients with splenectomy, pulmonary hypertension risk, and heart disease had higher GDF-15 levels than those without. GDF-15 was lower among hydroxyurea-treated patients. Multiple linear regression analysis revealed that transfusion index (p=0.012), serum ferritin (p < 0.001), tricuspid regurgitant jet velocity (p < 0.001), ejection fraction (p=0.01) and CIMT (p=0.007) were independently related to GDF-15. According to ROC curve analysis, the cutoff value of GDF-15 at 1500 pg/mL could differentiate patients with and without heart disease. CONCLUSION: GDF-15 would identify TI patients at increased risk of pulmonary and cardiovascular complications as well as subclinical atherosclerosis. PMID- 26142331 TI - Impact of eNOS polymorphisms on red blood cell aggregation in sickle cell disease. PMID- 26142332 TI - CD49d and CD26 are independent prognostic markers for disease progression in patients with chronic lymphocytic leukemia. AB - CLL is characterized by extremely variable clinical course. Several prognostic factors can predict disease progression and therapeutic outcomes in those patients. The aim was to evaluate the use of CD49d and CD26 as independent prognostic markers in CLL patients. The present study measured surface expression of CD49d and CD26 by three-color flow cytometry in a series of 103 untreated CLL patients. We evaluated the prognostic role of CD49d and CD26 to predict the risk of lymphocyte doubling, disease progression and overall survival. We confirmed that CD49d and CD26 were significant predictors of lymphocyte doubling(P<0.001 for both markers) and disease progression (P<0.001 for both markers) but insignificant for overall survival(P=0.303 and 0.519 respectively. Multivariate analysis between clinical parameters and flow cytometry markers revealed that CD49d and CD26 are independent prognostic markers for lymphocyte doubling (HR=1.487 P=007 and HR=2.248, P=0.014 respectively) and progression to a more advanced stage (HR=3.191, P=0.049 and HR=7.887, P=0.003). Also, concordant expression of both markers was found to improve their predictive power. Many studies reported that CD49d and CD26 combined analysis was found to improve their power to predict the risk of lymphocyte doubling and disease progression. CD49d and CD26 have independent prognostic value and we suggest its use as a part of routine panel for prognostic stratification of CLL. PMID- 26142333 TI - Intermediaries of branched chain amino acid metabolism induce fetal hemoglobin, and repress SOX6 and BCL11A, in definitive erythroid cells. AB - High levels of fetal hemoglobin (HbF) can ameliorate human beta-globin gene disorders. The short chain fatty acid butyrate is the paradigmatic metabolic intermediary that induces HbF. Inherited disorders of branched-chain amino acid (BCAA) metabolism have been associated with supranormal HbF levels beyond infancy, e.g., propionic acidemia (PA) and methylmalonic acidemia (MMA). We tested intermediaries of BCAA metabolism for their effects on definitive erythropoiesis. Like butyrate, the elevated BCAA intermediaries isovalerate, isobutyrate, and propionate, induce fetal globin gene expression in murine EryD in vitro, are associated with bulk histone H3 hyperacylation, and repress the transcription of key gamma globin regulatory factors, notably BCL11A and SOX6. Metabolic intermediaries that are elevated in Maple Syrup Urine Disease (MSUD) affect none of these processes. Percent HbF and gamma (gamma) chain isoforms were also measured in non-anemic, therapeutically optimized subjects with MSUD (Group I, n=6) or with Isovaleric Acidemia (IVA), MMA, or PA (Group II, n=5). Mean HbF was 0.24 +/- 0.15% in Group I and 0.87 +/- 0.13% in Group II (p=.01); only the Ggamma isoform was detected. We conclude that a family of biochemically related intermediaries of branched chain amino acid metabolism induces fetal hemoglobin during definitive erythropoiesis, with mechanisms that mirror those so far identified for butyrate. PMID- 26142334 TI - IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients: IL-10 polymorphism and plasma levels in leukemia patients. AB - Acute Lymphoblastic Leukemia is the leading form of cancer in infancy, and compelling evidences suggest an involvement of altered immune competence on this malignancy pathogenesis. Interleukin 10 (IL-10) is a pleiotropic cytokine designated as an immunosuppressive molecule, but may act as an immunostimulant factor in cancer development and progression. An IL-10 single nucleotide polymorphism (SNP) rs1800896 has been associated with disease progression to ALL, and might influence cytokine expression. This study analyzed the IL-10 rs1800896 polymorphism and performed a case-control study to determine the significant associations with ALL susceptibility and prognosis. IL-10 plasma levels were determined and associated with genotypes and disease phase. The study consisted of 67 childhood ALL patients and 75 age-related healthy controls. The rs1800896 was not associated with ALL susceptibility or risk of relapse. No significant association was observed between different genotypes of the rs1800896 and plasma levels of IL-10. Cytokine plasma levels were significantly higher in the diagnosis group (9.71 pg/mL +/- 3.7), comparing to the treatment (3.48 pg/mL +/- 1.3; p=0.01) and remission phase (0.12 pg/mL +/- 0.1; p=0.0001) groups. This work indicates that the IL-10 plasma expression is altered from ALL disease diagnosis and remission. Moreover, prospective studies will establish the functional role of IL-10 in immune modulation in childhood ALL. PMID- 26142335 TI - Effect of Quwan Chencuo Formula () on renal fibrosis in obstructive nephropathy rats. AB - OBJECTIVE: To observe the effect of Quwan Chencuo Formula(, QCF) on renal fibrosis in rats with obstructive nephropathy. METHODS: Twenty-four rats were randomly divided into three groups, 4 for sham operation as the control group, 10 for unilateral ureteral obstruction (UUO) model group, and the rest 10 for QCF treating UUO model group. All rats were sacrificed under 3% pentobarbital (50 mg/kg) anesthesia on the 14th day after surgery, then the right kidney samples of rats were harvested for hematoxylin eosin (HE) staining and Masson staining to observe the renal pathological changes. Immunohistochemistry and Western blotting were used to examine the expression of transforming growth factor beta1 (TGF beta1), and real-time polymerase chain reaction (RT-PCR) was employed to examine the expressions of TGF-beta1, alpha-smooth actin (alpha-SMA) and E-cadherin mRNA. RESULTS: HE and Masson staining showed that the renal interstitial of the rats in the control group had no significant fibrotic lesion; in the model group, there were obvious interstitial fibrosis; for the QCF group, there were epithelial cell necrosis, infiltration of lymphocytes and mononuclear cells, aggravated interstitial fibrosis in varied degrees, but the pathological changes were less in the QCF group than in the model group. The immunohistochemistry and Western blotting results showed that the TGF-beta1 expression was increased significantly in the model group, while decreased significantly in the QCF group (P<0.05); RT PCR showed that the mRNA expression of alpha-SMA and TGFbeta1 increased significantly in the model group, while both were significantly decreased in the QCF group compared with the model group (P<0.05). The mRNA expression of E cadherin was decreased significantly in the model group, and it was significantly increased in the QCF group as compared with the model group <0.05). CONCLUSION: QCF may improve renal fibrosis by regulating the expressions of TGF-beta1, alpha SMA and E-cadherin, and prevent the progress of kidney fibrosis. PMID- 26142336 TI - Shen-Jing as a Chinese medicine concept might be a counterpart of stem cells in regenerative medicine. AB - As the epitome of the modern regenerative medicine, stem cells were proposed in the basic sense no more than 200 years ago. However, the concept of "stem cells" existed long before the modern medical description. The hypothesis that all things, including our sentient body, were generated from a small origin was shared between Western and Chinese people. The ancient Chinese philosophers considered Jing (also known as essence) as the origin of life. In Chinese medicine (CM), Jing is mainly stored in Kidney (Shen) and the so-called Shen-Jing (Kidney essence). Here, we propose that Shen-Jing is the CM term used to express the meaning of "origin and regeneration". This theoretical discovery has at least two applications. First, the actions underlying causing Shen-Jing deficiency, such as excess sexual intercourse, chronic diseases, and aging, might damage the function of stem cells. Second, a large number of Chinese herbs with Shen-Jing nourishing efficacy had been proven to affect stem cell proliferation and differentiation. Therefore, if Shen-Jing in CM is equivalent with stem cells in regenerative medicine, higher effective modulators for regulating stem-cell behaviors from Kidney-tonifying herbs would be expected. PMID- 26142337 TI - Adjuvant effects of fermented red ginseng extract on advanced non-small cell lung cancer patients treated with chemotherapy. AB - OBJECTIVE: To investigate the adjuvant therapeutic effects of fermented red ginseng (FRG) extract on non-small cell lung cancer (NSCLC) patients treated with chemotherapy. METHODS: A total of 60 patients with advanced NSCLC were divided into two groups using a random number table, i.e., the gemcitabine plus cisplatin (GP) chemotherapy alone group (26 patients) and the FRG + GP chemotherapy group (34 patients), for 60-day treatment. Patients were then assessed according to the Fatigue Symptom Inventory, Chinese medicine symptoms score, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Karnofsky Performance Status Scale, and Functional Assessment of Cancer Therapy-Lung. In addition, chemotherapy toxicity and tumor biomarkers were measured. RESULTS: For NSCLC patients after chemotherapy, FRG extract significantly improved the FSI score, CM symptoms score, psychological status, physical conditions, and quality of life and reduced chemotherapy toxicity, but the expression levels of carcinoembryonic antigen, cytokeratin-19 fragments, and neuron-specific enolase were not significantly different between the chemotherapy alone and the FRG + chemotherapy groups or between pre- and post-treatments. CONCLUSIONS: This study demonstrated that FRG extract had an adjuvant effect on advanced NSCLC patients treated with chemotherapy. Further studies with a larger sample size will verify the current findings. PMID- 26142338 TI - Governor vessel moxibustion: Ancient Chinese medical technology with new vitality. AB - Moxibustion is an ancient therapeutic technique used in Chinese medicine. Governor Vessel moxibustion (GVM) was developed from long snake moxibustion, a popular technique used in China's Jiangsu and Zhejiang Provinces, and is significantly more effective than general moxibustion. We aimed to review GVM, including its theoretical basis, choices of moxibustion points and materials, operation procedures, clinical applications, and contraindications. This information could increase the appropriate use of GVM and support further in depth research. PMID- 26142339 TI - Heijiangdan ointment relieves oxidative stress from radiation dermatitis induced by (60)Co gamma-ray in mice. AB - OBJECTIVE: To investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co gamma-ray radiation-induced dermatitis in mice. METHODS: Female Wistar mice with grade 4 radiation dermatitis induced by (60)Co gamma-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor beta1 (TGF beta1) were analyzed by western blot. RESULTS: Compared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-beta1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-beta1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-beta1 and the difference was marked as compared with the untreated and negative control groups (P<0.05). CONCLUSION: HJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice. PMID- 26142340 TI - Berberine induces cell apoptosis through cytochrome C/apoptotic protease activating factor 1/caspase-3 and apoptosis inducing factor pathway in mouse insulinoma cells. AB - OBJECTIVE: To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells. METHODS: Different concentrations of berberine were used to treat mouse insulinoma (MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro- and anti-apoptosis proteins were detected by western-blotting. RESULTS: The half-maximal inhibitory concentration (IC50) of berberine was 5.7 MUmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction (P<0.05) in cell number after only 4-h incubation; which reached 50% after 24 h (P<0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9- and 4.6-fold after treating with berberine (5 MUmol/L) for 8 and 16 h, while 3- and 8.7-fold after 10 MUmol/L treatment for 8 and 16 h (P<0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1 (Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade. CONCLUSION: High concentration (5 and 10 MUmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf 1/caspase-3 and apoptosis inducing factor (AIF) pathway. PMID- 26142341 TI - Effect of Danlou Tablet () on peri-procedural myocardial injury among patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndrome: A study protocol of a multicenter, randomized, controlled trial. AB - BACKGROUND: It has been shown that administration of statins reduced the risk of peri-procedural myocardial damage. However, it remains unclear whether Chinese medicine Danlou Tablet (), similar to statins, may protect patients undergoing percutaneous coronary intervention (PCI) from peri-procedural myocardial damage. OBJECTIVE: To demonstrate the hypothesis whether treatment with Danlou Tablet would improve clinical outcome in patients undergoing selective PCI with non-ST elevation acute coronary syndrome (NSTE-ACS) in China. METHODS: Approximately 220 patients with unstable angina or non-ST-segment elevation myocardial infarction undergoing PCI will be enrolled and randomized to Danlou Tablet treatment (4.5 g/day for 2 days before intervention, with a further 4.5 g/day for 90 days thereafter) or placebo. All patients will not receive Danlou Tablet before procedure. The primary end point is to evaluate the incidence of cardiac death, myocardial infarction or unplanned re-hospitalization and revascularization after 30 days in patients undergoing selective PCI treated with Danlou Tablet compared with placebo. Secondary endpoints include the incidence of peri-procedural myocardial injury, 3-month clinical outcomes, the quality of life and Chinese medicine syndromes assessment. CONCLUSION: This study protocol will provide important evidence of Danlou Tablet treatment on the peri-procedural myocardial injury in patients with NSTE-ACS undergoing selective PCI, which may support a strategy of routine Danlou Tablet therapy to improve the clinical outcomes. PMID- 26142342 TI - Application of photoluminescent bioceramic material for different chronic illnesses by selecting "trigger points" and "propagated sensation along meridians" phenomenon. AB - OBJECTIVE: To investigate the practicability on the processes of selecting "local tenderness skin points (trigger points)" and "propagated sensation along meridians" (PSM) phenomenon, and to find out the corresponding abnormal meridian channel in different illnesses. METHODS: Ten patients with different kinds of chronic illnesses were administered photoluminescent bioceramic material (PLB) irradiations on meridians. The processes of selecting trigger points and PSM phenomenon were carried out on 80% (8/10) of the cases to find out the corresponding abnormal meridian channel in different illnesses. There were 8 cases identified by trigger points selection; 3 cases identified by PSM; 2 were not identified by either trigger points or PSM. These 2 cases were tested with electrodermal measurements of the 24 Ryodoraku meridian points to select their corresponding abnormal meridian channels for PLB irradiations. Objective and subjective Clinical improvements after PLB irradations were recorded. RESULTS: After PLB treatment, patients showed different noticeable improvements upon clinical observations. The most significant improvements were noticed shortly after subacute stage at 3-5 months durations of illnesses. Objective measurements showed a clinical improvement of 43.8%. CONCLUSIONS: To explain our clinical observations, we simply deduced that PLB treatment induced or promoted fluid/water diffusion along meridian channels. There was a gradually dredging of the meridian channels thus relieving stagnation and a vital change in the flow of dynamic patterns of meridians. This conforms to, or validates, the old traditional Chinese theory of "Bu Tong Ze Tong" and "Tong Ze Bu Tong", that is, where there is obstruction, there is pain; where there is no obstruction, there is no pain. PMID- 26142343 TI - Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca2+ channels. AB - Autism is a neurodevelopmental psychiatric disorder characterized by impaired reciprocal social interaction, disrupted communication, and restricted and stereotyped patterns of interests. Autism is known to have a strong genetic component. Although mutations in several genes account for only a small proportion of individuals with autism, they provide insight into potential biological mechanisms that underlie autism, such as dysfunction in Ca(2+) signaling, synaptic dysfunction, and abnormal brain connectivity. In autism patients, two mutations have been reported in the Rab3 interacting molecule 3 (RIM3) gene. We have previously demonstrated that RIM3 physically and functionally interacts with voltage-dependent Ca(2+) channels (VDCCs) expressed in neurons via the beta subunits, and increases neurotransmitter release. Here, by introducing corresponding autism-associated mutations that replace glutamic acid residue 176 with alanine (E176A) and methionine residue 259 with valine (M259V) into the C2B domain of mouse RIM3, we demonstrate that both mutations partly cancel the suppressive RIM3 effect on voltage-dependent inactivation of Ba(2+) currents through P/Q-type CaV2.1 recombinantly expressed in HEK293 cells. In recombinant N-type CaV2.2 VDCCs, the attenuation of the suppressive RIM3 effect on voltage-dependent inactivation is conserved for M259V but not E176A. Slowing of activation speed of P/Q-type CaV2.1 currents by RIM3 is abolished in E176A, while the physical interaction between RIM3 and beta subunits is significantly attenuated in M259V. Moreover, increases by RIM3 in depolarization induced Ca(2+) influx and acetylcholine release are significantly attenuated by E176A in rat pheochromocytoma PC12 cells. Thus, our data raise the interesting possibility that autism phenotypes are elicited by synaptic dysfunction via altered regulation of presynaptic VDCC function and neurotransmitter release. PMID- 26142344 TI - Na+-Ca2+ exchanger mediates ChR2-induced [Ca2+]i elevation in astrocytes. AB - Intracellular Ca(2+) elevation resulting from different Ca(2+) pathways may play different roles in astrocyte functions. Channelrhodopsin-2 (ChR2), a light-gated cation channel, has been used to selectively stimulate astrocytes by inducing intracellular Ca(2+) ([Ca(2+)]i) elevation, but the exact underlying mechanism is still unclear. We found that in the absence of extracellular Ca(2+), light stimulation failed to induce [Ca(2+)]i elevation in astrocytes expressed ChR2. Pharmacological experiments excluded the involvement of Ca(2+)-induced Ca(2+) release from intracellular stores. Further experiments demonstrated that the ChR2 induced [Ca(2+)]i elevation was mainly mediated by reversal of the Na(+)-Ca(2+) exchanger following Na(+) influx through ChR2 channels. Since intracellular Na(+) homeostasis plays important roles in astrocytes, including the modulation of [Ca(2+)]i, neurotransmitter uptake and cell metabolism, our results indicate that ChR2 is a good candidate which could be used for mimicking the intracellular Na(+) disturbance in astrocytes that occurs in various physiological and pathological processes including the uptake of neurotransmitters and ischemia, as well as the activities of various cation channels, ion exchangers, and pumps. PMID- 26142346 TI - Efficacy and Safety of Weekly Paclitaxel Therapy for Advanced Gastric Cancer Patients with Disseminated Intravascular Coagulation. PMID- 26142345 TI - Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation. AB - OBJECTIVE: Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes. METHOD: In two randomized smoking cessation trials comparing cNRT vs. placebo, and varenicline vs. placebo, we used logistic regression to model associations between CHRNA5 rs16969968 and abstinence at end of treatment. RESULTS: For abstinence at end of treatment, there was an interaction between cNRT and rs16969968 (X(2)=8.15, df=2, omnibus-p=0.017 for the interaction); individuals with the high-risk AA genotype were more likely to benefit from cNRT. In contrast, varenicline increased abstinence, but its effect did not vary with CHRNA5. However, the genetic effects differed between the placebo control groups across two trials (wald=3.94, df=1, p=0.047), this non replication can alter the interpretation of pharmacogenetic findings. CONCLUSIONS: Results from two complementary smoking cessation trials demonstrate inconsistent genetic results in the placebo arms. This evidence highlights the need to compare the most effective pharmacotherapies with the same placebo control to establish pharmacogenetic evidence to aid decisions on medication choice for patients trying to quit smoking. PMID- 26142347 TI - Laparoscopic hysteropexy versus vaginal hysterectomy for the treatment of uterovaginal prolapse: a prospective randomized pilot study. AB - INTRODUCTION AND HYPOTHESIS: We have previously reported on laparoscopic hysteropexy for uterine prolapse. We now report a pilot randomized study comparing laparoscopic hysteropexy (LH) with vaginal hysterectomy (VH) for the surgical management of uterine prolapse. METHODS: Women with symptomatic uterine prolapse requiring surgery for uterine prolapse were recruited. The data were analyzed for those who had completed a 1-year follow-up. As this is a pilot randomized study, no power calculation was available. The main primary outcome measure was repeat apical prolapse. Secondary outcomes included operation data, complications, recovery time, functional and QoL outcomes, and anatomical outcomes. Wilcoxon signed rank and Mann-Whitney tests compared pre-operative with post-operative data and the difference between the two groups respectively. RESULTS: One hundred and thirty-two women were recruited. Of these, 101 were randomized. Eighty percent of the 31 women who dropped out preferred LH. One-year follow-up data were analyzed for 37 women in the LH and 35 women in the VH group. Time before return to normal activity was significantly shorter, estimated blood loss was significantly less, pain score 24 h post-operatively was significantly lower, and hospital stay was significantly shorter in the hysteropexy group compared with the vaginal hysterectomy group. Operation time was significantly longer in the hysteropexy group. Both procedures showed significant improvement in prolapse symptoms. Hysteropexy was associated with better apical support; point C and total vaginal length were significantly improved. More vaginal repairs were subsequently required post-hysteropexy. CONCLUSIONS: Laparoscopic hysteropexy is a safe surgical alternative to vaginal hysterectomy with a similar risk of repeat apical surgery at 1 year. Longer follow-up data from larger studies are required. PMID- 26142348 TI - Perineorrhaphy: commonly performed yet poorly understood. A survey of surgeons. AB - INTRODUCTION AND HYPOTHESIS: Perineorrhaphy is performed for the prevention of recurrent prolapse, improved sexual function, treatment of pain, and cosmesis. Its use is based on expert opinion with few objective data. We aimed to describe factors that are important to surgeons when deciding to perform perineorrhaphy and variations in surgical technique. METHODS: We administered an anonymous survey to surgeon attendees at the 2014 SGS annual scientific meeting regarding which factors are important when deciding to perform a perineorrhaphy and details of their surgical technique. Surgeons rated the importance of factors; one-way ANOVA was used to rank the decision factors and post hoc pairwise comparisons with Fisher's least significant difference method were used to evaluate the importance between factors. RESULTS: A total of 183 out of 360 surgeon attendees responded. Most were between ages 36 and 60 (79 %), 56 % were female, 64 % practiced in an academic environment, and 64 % had undergone subspecialty training. An enlarged genital hiatus (GH) ranked as the most important factor influencing the decision to perform a perineorrhaphy, followed by a concomitant prolapse procedure (p < 0.001). Sexual function and cosmesis were rated as being less important. The decision to perform perineorrhaphy was made with the patient in 65 % of cases, and otherwise in the operating room. Significant heterogeneity exists regarding surgeon suture preference and how muscles were re-approximated. Most (81 %) reported incorporating structures both proximal and distal to the hymen in their repairs. CONCLUSION: Genital hiatus size and concomitant prolapse procedures ranked highest in surgeons' decision to perform a perineorrhaphy. Significant heterogeneity exists in the indications for and technique used to perform perineorrhaphy. PMID- 26142349 TI - Vesicouterine fistula and concomitant ureteric necrosis following uterine artery embolization for fibroid uterus. PMID- 26142350 TI - Retrospective comparison between the Prolift and Elevate anterior vaginal mesh procedures: 18-month clinical outcome. AB - INTRODUCTION AND HYPOTHESIS: There are few direct comparisons between the first generation trocar-guided and the second-generation single-incision mesh systems in the treatment of anterior pelvic organ prolapse (POP). Hence, the purpose of this retrospective review was to compare 18-month operative success in female patients who had undergone POP surgery with the anterior Prolift (n = 52) or the anterior Elevate mesh (n = 62). METHODS: Subjective (bulge symptoms) and objective measures (absence of anterior or apical descent beyond the hymen, POP-Q anterior stage 0 or I, no retreatment for POP) were used as the measures of surgical efficacy. Postoperative pelvic floor pain, dyspareunia, de novo overactive bladder (OAB), de novo stress urinary incontinence (SUI), and mesh exposure were addressed as complications of POP surgery. RESULTS: The two groups did not differ with regard to the subjective and objective measures of the operative efficacy. There were no between-group differences in the proportion of women reporting postoperative pelvic floor pain, dyspareunia, de novo SUI, and de novo OAB symptoms (all p values >0.05). The proportion of patients with postoperative vaginal exposure was significantly higher in the Prolift group (7.7 %) than in the Elevate group (0.0 %; p = 0.02). CONCLUSIONS: In conclusion, our results suggest that the use of the Elevate system in patients with anterior compartment prolapse results in fewer mesh erosions, but similar efficacy, compared with the Prolift mesh. PMID- 26142351 TI - Global health education in Swedish medical schools. AB - AIMS: Global health education is increasingly acknowledged as an opportunity for medical schools to prepare future practitioners for the broad health challenges of our time. The purpose of this study was to describe the evolution of global health education in Swedish medical schools and to assess students' perceived needs for such education. METHODS: Data on global health education were collected from all medical faculties in Sweden for the years 2000-2013. In addition, 76% (439/577) of all Swedish medical students in their final semester answered a structured questionnaire. RESULTS: Global health education is offered at four of Sweden's seven medical schools, and most medical students have had no global health education. Medical students in their final semester consider themselves to lack knowledge and skills in areas such as the global burden of disease (51%), social determinants of health (52%), culture and health (60%), climate and health (62%), health promotion and disease prevention (66%), strategies for equal access to health care (69%) and global health care systems (72%). A significant association was found between self-assessed competence and the amount of global health education received (p<0.001). A majority of Swedish medical students (83%) wished to have more global health education added to the curriculum. CONCLUSIONS: Most Swedish medical students have had no global health education as part of their medical school curriculum. Expanded education in global health is sought after by medical students and could strengthen the professional development of future medical doctors in a wide range of topics important for practitioners in the global world of the twenty-first century. PMID- 26142354 TI - The Difference a Decade Makes. PMID- 26142352 TI - Specifying the core network supporting episodic simulation and episodic memory by activation likelihood estimation. AB - It has been suggested that the simulation of hypothetical episodes and the recollection of past episodes are supported by fundamentally the same set of brain regions. The present article specifies this core network via Activation Likelihood Estimation (ALE). Specifically, a first meta-analysis revealed joint engagement of expected core-network regions during episodic memory and episodic simulation. These include parts of the medial surface, the hippocampus and parahippocampal cortex within the medial temporal lobes, and the temporal and inferior posterior parietal cortices on the lateral surface. Both capacities also jointly recruited additional regions such as parts of the bilateral dorsolateral prefrontal cortex. All of these core regions overlapped with the default network. Moreover, it has further been suggested that episodic simulation may require a stronger engagement of some of the core network's nodes as well as the recruitment of additional brain regions supporting control functions. A second ALE meta-analysis indeed identified such regions that were consistently more strongly engaged during episodic simulation than episodic memory. These comprised the core-network clusters located in the left dorsolateral prefrontal cortex and posterior inferior parietal lobe and other structures distributed broadly across the default and fronto-parietal control networks. Together, the analyses determine the set of brain regions that allow us to experience past and hypothetical episodes, thus providing an important foundation for studying the regions' specialized contributions and interactions. PMID- 26142353 TI - Introduction to desiccation biology: from old borders to new frontiers. AB - MAIN CONCLUSION: A special issue reviews the recent progress made in our understanding of desiccation tolerance across various plant and animal kingdoms. It has been known for a long time that seeds can survive near absolute protoplasmic dehydration through air drying and complete germination upon rehydration because of their desiccation tolerance. This property is present both in prokaryotes and eukaryotes across all life kingdoms. These dry organisms suspend their metabolism when dry, are extremely tolerant to acute environmental stresses and are relatively stable during long periods of desiccation. Studies aiming at understanding the mechanisms of survival in the dry state have emerged during the past 40 years, moving from in vitro to genomic models and comparative genomics, and from a view that tolerance is an all-or-nothing phenomenon to a quantitative trait. With the prospect of global climate change, understanding the mechanisms of desiccation tolerance appears to be a promising avenue as a prelude to engineering crops for improved drought tolerance. Understanding desiccation is also useful for seed banks that rely on dehydration tolerance to preserve plant genetic resources in the form of these propagules. Articles in this special issue explore the recent progress in our understanding of desiccation tolerance, including the evolutionary mechanisms that have been adopted across various plant (algae, lichens, seeds, resurrection plants) and animal model systems (Caenorhabditis elegans, brine shrimp). We propose that the term desiccation biology defines the discipline dedicated to understand the desiccation tolerance in living organisms as well as the limits and time constraints thereof. PMID- 26142355 TI - Supporting the Use of Health Technology Assessments by Decision-Makers. AB - A perceived gap exists in how well Canadian health technology assessment (HTA) producers are supporting the use of their HTAs by decision-makers. The authors propose that the newly released HTA Database Canadian search interface incorporate structured decision-relevant summaries of HTAs that would be developed by participating Canadian HTA organizations. The registry would serve as a "one-stop shop" by including HTA reports along with their structured summaries in a format that better meets decision-makers' needs. The Health Technology Analysis Exchange - a Canadian network of publicly funded HTA producers - is well-positioned to undertake this work and would welcome input about both the idea and its execution. PMID- 26142356 TI - Regulating Direct-to-Consumer Drug Information: A Case Study of Eli Lilly's Canadian 40over40 Erectile Dysfunction Campaign. AB - Like most jurisdictions, Canada prohibits direct-to-consumer advertising (DTCA) of prescribed drugs. However, direct-to-consumer information (DTCI) is permitted, allowing companies to inform the public about medical conditions. An analysis of Eli Lilly's 40over40 promotion campaign for erectile dysfunction (ED), which included a quiz on ED, shows that DTCI, like DTCA, can be an effective means of drug familiarization. The pharmaceutical industry is "playing by the rules" currently in effect in Canada. Regulators should thus seriously consider whether existing rules permitting DTCI actually meet stated objectives of protecting the public from marketing campaigns (i.e., DTCA) that may deliver misleading information. PMID- 26142357 TI - A National Approach to Reimbursement Decision-Making on Drugs for Rare Diseases in Canada? Insights from Across the Ponds. AB - INTRODUCTION: Regardless of the type of health system or payer, coverage decisions on drugs for rare diseases (DRDs) are challenging. While these drugs typically represent the only active treatment option for a progressive and/or life-threatening condition, evidence of clinical benefit is often limited because of small patient populations and the costs are high. Thus, decisions come with considerable uncertainty and risk. In Canada, interest in developing a pan Canadian decision-making approach informed by international experiences exists. OBJECTIVE: To develop an inventory of existing policies and processes for making coverage decisions on DRDs around the world. METHODS: A systematic review of published and unpublished documents describing current policies and processes in the top 20 gross domestic product countries was conducted. Bibliographic databases, the Internet and government/health technology assessment organization websites in each country were searched. Two researchers independently extracted information and tabulated it to facilitate qualitative comparative analyses. Policy experts from each country were contacted and asked to review the information collected for accuracy and completeness. RESULTS: Almost all countries have multiple mechanisms through which coverage for a DRD may be sought. However, they typically begin with a review that follows the same process as drugs for more common conditions (i.e., the centralized review process), although specific submission requirements could differ (e.g., no need to submit a cost-effectiveness analysis). When drugs fail to receive a positive recommendation/decision, they are reconsidered by "safety net"-type programs. Eligibility criteria vary across countries, as do the decision options, which may be applied to individual patients or patient groups. CONCLUSIONS: With few exceptions, countries have not created separate centralized review processes for DRDs. Instead, they have modified components of existing mechanisms and added safety nets. PMID- 26142358 TI - Estimating Nursing Wage Bill in Canada and Breaking Down the Growth Rate: 2000 to 2010. AB - Even though the nursing professional category (registered nurses [RNs] and licensed practical nurses) made up about one-third of the Canadian health professionals, no study exists about their wage bill, the composition and growth rate of this wage bill. This paper attempts to fill this gap by estimating the nursing wage bill in the Canadian provinces and breaking down the growth rate for the 2000-2010 period, using the 2001 Census and the 2011 National Household Survey. Total wage bill for the nursing professional category in Canada was estimated at $20.1 billion ($17.3 billion for RNs), which suggests that it is as substantial as net physician remuneration. The average annual growth rate of this wage bill was 6.6% for RNs. This increase was mainly driven by real (inflation adjusted) wage per hour, which was 3.0%, suggesting the existence of a "health premium" of 1.7 percentage points during the study period. PMID- 26142359 TI - The Impact of Private Insurance Coverage on Prescription Drug Use in Ontario, Canada. AB - Canadians obtain prescription drug coverage through a patchwork of public insurance, private benefit plans and out-of-pocket payments. Prior evidence suggests that insurance coverage, in general, leads to higher utilization rates of essential medicines; it is unclear whether individuals with private insurance have better access to medicines. Using data from the 2008 Canadian Community Health Survey, we identified cohorts from Ontario who reported having been diagnosed by a physician with asthma, high blood pressure or diabetes. Using propensity score stratification techniques, we compared drug utilization of individuals holding private insurance with that of individuals holding either public insurance (for those aged over 65 years) or no insurance (aged under 65 years). In five out of six comparisons, individuals with private insurance were more likely to take prescribed drugs than those without. Raw differences in the percentage of patients taking medicines ranged from 0.1 to 8.1%. Ontarians with chronic conditions holding private drug insurance are more likely to use prescription drugs than those who do not. Whether these inequities result in health outcome differences remains unknown. PMID- 26142361 TI - Enzymatic synthesis of hyaluronan hybrid urinary trypsin inhibitor. AB - Human urinary trypsin inhibitor is a proteoglycan that has a single low-sulfated chondroitin 4-sulfate chain at the seryl residue in position 10 of the core protein as a glycosaminoglycan moiety, and is used as an anti-inflammatory medicine based on the protease inhibitory activity of the core protein. However, the functions of the glycosaminoglycan moiety have not yet been elucidated in detail. In the present study, the glycosaminoglycan chains of a native urinary trypsin inhibitor were remodeled to hyaluronan chains, with no changes to the core protein, using transglycosylation as a reverse reaction of the hydrolysis of bovine testicular hyaluronidase, and the properties of the hybrid urinary trypsin inhibitor were then analyzed. The trypsin inhibitory activitiy of the hyaluronan hybrid urinary trypsin inhibitor was similar to that of the native type; however, its inhibitory effect on the hydrolysis of hyaluronidase were not as strong as that of the native type. This result demonstrated that the native urinary trypsin inhibitor possessed hyaluronidase inhibitory activity on its chondroitin sulfate chain. The hyaluronan hybrid urinary trypsin inhibitors obtained affinity to a hyaluronan-binding protein not exhibited by the native type. The interactions between the hyaluronan hybrid urinary trypsin inhibitors and phosphatidylcholine (abundant in the outer layer of plasma membrane) were stronger than that of the native type. Hyaluronan hybrid urinary trypsin inhibitors may be useful for investigating the functions of the glycosaminoglycan chains of urinary trypsin inhibitors and hyaluronan, and our hybrid synthesizing method may be used widely in research for future medical applications. PMID- 26142362 TI - Primary gastric extranodal natural killer/T-cell lymphoma, nasal type, with acquisition of CD20 expression in the subcutaneous relapse: report of a case with literature review. PMID- 26142360 TI - Focal adhesion kinase and its role in skeletal muscle. AB - Skeletal muscle has a remarkable ability to respond to different physical stresses. Loading muscle through exercise, either anaerobic or aerobic, can lead to increases in muscle size and function while, conversely, the absence of muscle loading stimulates rapid decreases in size and function. A principal mediator of this load-induced change is focal adhesion kinase (FAK), a downstream non receptor tyrosine kinase that translates the cytoskeletal stress and strain signals transmitted across the cytoplasmic membrane by integrins to activate multiple anti-apoptotic and cell growth pathways. Changes in FAK expression and phosphorylation have been found to correlate to specific developmental states in myoblast differentiation, muscle fiber formation and muscle size in response to loading and unloading. With the capability to regulate costamere formation, hypertrophy and glucose metabolism, FAK is a molecule with diverse functions that are important in regulating muscle cell health. PMID- 26142363 TI - Left Main Coronary Artery Occlusion and the Collateral-Dependent Heart. PMID- 26142364 TI - Aortic Valve Thrombus in a Patient With an Extracorporeal Left Ventricular Assist Device: The Dilemma of Management. PMID- 26142365 TI - Transesophageal Echocardiography Guidance of Antegrade Cardioplegia Delivery for Cardiac Surgery. AB - OBJECTIVES: The initial volume of antegrade cardioplegia used to induce asystole during aortic cross-clamp still is based on empiric methods and may be excessive, potentially leading to hyperkalemia, myocardial edema, and acute left ventricular distention from aortic regurgitation. The objectives were to determine whether the volume of cardioplegia required to induce asystole is proportional to left ventricular mass, and whether the degree of left ventricular distention is proportional to the severity of aortic regurgitation. DESIGN: Prospective observational study. SETTING: Two tertiary university hospitals. INTERVENTIONS: Transesophageal echocardiography was used to estimate left ventricular mass (prolate ellipse revolution formula), quantify aortic regurgitation, and monitor for distention during initial antegrade cardioplegia delivery. The volume of cardioplegia required for asystole was recorded. PARTICIPANTS: Fifty-eight patients aged over 18 years scheduled for cardiac surgery requiring aortic cross clamping. MEASUREMENTS AND MAIN RESULTS: There was a weak correlation of left ventricular mass and antegrade cardioplegia volume required for asystole (r = 0.35, p = 0.047). The degree of left ventricular distention correlated moderately with the severity of aortic regurgitation (r = 0.55, p = 0.007) and was excessive and stopped early (aborted) in 24% of all patients, including 18% of 39 patients without aortic regurgitation. An aortic regurgitation vena contracta of 0.3 cm predicted aborted cardioplegia with modest accuracy (AUC 0.81, 0.66-0.99, p = 0.02, sensitivity 71%, specifity 81%). CONCLUSIONS: Estimated left ventricular mass is not a useful predictor of the initial volume of antegrade cardioplegia required to induce asystole. However transesophageal echocardiography can predict and monitor for left ventricular distention, which is common. PMID- 26142366 TI - Strategies for Temporary Cardiac Pacing in Pediatric Patients With Postoperative Junctional Ectopic Tachycardia. PMID- 26142367 TI - Pulmonary Artery Acceleration Time in Cardiac Surgical Patients. AB - OBJECTIVES: To examine the potential for using pulmonary Doppler to assess the hydraulic forces opposing right ventricular ejection in a perioperative setting. DESIGN: A prospective, observational study. SETTING: A university hospital tertiary-care center. PARTICIPANTS: Participants included 74 patients: 62 undergoing coronary artery bypass grafting and 12 undergoing mitral valve surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After induction of anesthesia, a pulmonary artery catheter was used to assess pulmonary artery pressures, cardiac output, and pulmonary vascular resistance. Transesophageal echocardiography was performed to measure pulsed-wave Doppler-derived acceleration time (AT) in 3 locations: the right ventricular outflow tract, the main pulmonary artery, and the right pulmonary artery. Flow reversal was observed in the main pulmonary artery in 96% of patients and possibly was responsible for the shorter ATs seen in this location. The best correlations between AT and pulmonary hemodynamic parameters were found in the right pulmonary artery. The relationships were strengthened in a subgroup of patients with elevated pulmonary capillary wedge pressure (PCWP). An acceleration time of 90 ms was associated with elevated pulmonary artery pressure and pulmonary vascular resistance. CONCLUSIONS: Flow reversal occurred frequently in the main pulmonary artery. AT in the right pulmonary artery yielded the best correlation with invasive hemodynamic parameters that were strengthened in patients with elevated PCWP. The addition of a PCWP measurement improved the reliability of AT in this patient population. PMID- 26142368 TI - Novel Navigated Ultrasound Compared With Conventional Ultrasound for Vascular Access-a Prospective Study in a Gel Phantom Model. AB - OBJECTIVES: The authors hypothesized that, compared with conventional ultrasound (CUS), the use of a novel navigated ultrasound (NUS) technology would increase success rates and decrease performance times of vascular access procedures in a gel phantom model. DESIGN: A prospective, randomized, crossover study. SETTING: A university Hospital. PARTICIPANTS: Participants were 44 anesthesiologists with varying clinical experience. INTERVENTIONS: Anesthesiologists performed in-plane and out-of-plane vascular access procedures using both NUS and CUS for needle visualization in a gel phantom model. MEASUREMENTS AND MAIN RESULTS: Procedure time was measured from needle insertion to verbalization of final needle positioning by the participants, and successful needle placement into the simulated vessel was verified by aspiration of simulated blood. By employing ultrasound navigation capabilities in addition to real-time ultrasound imaging during in-plane/long-axis vascular access procedures, median procedure time showed a nonsignificant decrease (7.5 seconds v 13.0 seconds; p = 0.028), and the observed increase in procedure success rate (90.9% v 100%; p = 0.125) did not reach statistical significance. For out-of-plane/short-axis vascular access procedures, a significant reduction in median procedure time (5.0 seconds v 11.5 seconds; p<0.001) and a significant increase in procedure success rate (75% v 100%; p<0.001) were achieved by using navigation technology combined with real time ultrasound. CONCLUSIONS: NUS technology improved the performance times and success rates of vascular access procedures conducted by anesthesiologists in a gel phantom model. PMID- 26142369 TI - Bedside Ultrasonographic Measurement of the Inferior Vena Cava. PMID- 26142370 TI - Response to Letter Regarding Bedside Ultrasonographic Measurement of the Inferior Vena Cava. PMID- 26142371 TI - Mobilization of copper ions in human peripheral lymphocytes by catechins leading to oxidative DNA breakage: A structure activity study. AB - Epidemiological studies suggest that dietary consumption of plant polyphenols is related to a lower incidence of various cancers. Among these compounds catechins (present in green tea and other beverages) are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. Thus these compounds can be used as leads to synthesize novel anticancer drugs with greater bioavailability. In view of this in this paper we have examined the chemical basis of cytotoxicity of catechins by studying the structure-activity relationship between catechin (C), epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG). Using single cell alkaline gel electrophoresis (comet assay) we have established the relative efficiency of cellular DNA breakage as EGCG>EGC>EC>C. We also show that cellular DNA breakage is the result of mobilization of copper ions bound to chromatin and the generation of reactive oxygen species. Further the relative DNA binding affinity order was confirmed using molecular docking and thermodynamic studies by studying the interaction of catechins with calf thymus DNA. The results suggest that the synthesis of any novel anti cancer molecule based on the structure of catechins should have as many galloyl moieties as possible resulting in an increased number of hydroxyl groups that may facilitate the binding of the molecule to cellular DNA. PMID- 26142372 TI - Electron microscopy: the coming of age of a structural biology technique. PMID- 26142373 TI - Embodied Knowledge and Making Sense of Prenatal Diagnosis. AB - Open-ended, qualitative interviews with women to whom amniocentesis was offered were analyzed to understand how women made sense of these tests. We found that women, whether tested or not, negotiated with biomedical information. They transformed it through identifiable processes, then wove it with their own instincts and beliefs and with their personal experiences, thereby creating "embodied" knowledge on which their decisions were based. Women who were and were not tested may have differed from each other when categorized on the basis of a final, binary choice, but they were more alike than unalike in reaching this point. The apparent importance of embodied knowledge suggests the critical role of the listening activities of the genetic counselor and of awareness of the validity and importance of women's complementary ways of knowing and doing in understanding the uses and meanings of prenatal genetic testing. PMID- 26142374 TI - Genetic Counseling: Clinical Geneticists' Views. AB - Evaluation of genetic counseling requires a clear consensus about its objectives, which is not evident in published definitions and guidelines. This study aims to investigate clinical geneticists' beliefs and thoughts about their practice. Structured interviews with eight clinical geneticists addressed the aims, skills, and expectations of genetic counseling. Analysis of transcribed interviews revealed four key themes, with contradictory aspects: 1. Providing information that is objective, full, and accurate versus information that is contingent on circumstances and tailored to individual needs. 2. Eliciting emotion and dealing with it directly versus dampening down and containing emotion. 3. Communicating nondirectively versus directively. 4. Expecting to perform a range of sophisticated tasks while having minimal training in the necessary skills to achieve these. These results have implications for the nature of the professional role, the development of training required for it, and the evaluation of genetic counseling. PMID- 26142375 TI - Genetic Testing Considerations in Breast Cancer Patients. AB - Genetic testing is now feasible for a growing number of cancers. Although the implications for unaffected relatives have been widely described, the impact of the tests on affected individuals are often not recognized. We present and discuss four cases that highlight some of the issues-for example, feelings of guilt and anxiety, intrafamilial conflict, and support needs-that may arise in testing affected individuals. We offer some suggestions to aid in the approach to such testing. PMID- 26142376 TI - Are General Practitioners Willing and Able to Provide Genetic Services for Common Diseases? AB - Primary care in the United Kingdom has been advocated as an optimal location for the provision of genetic services for common diseases. Little, however, is known about general practitioners' own views toward this suggestion or the possible demand for such services from patients. To assess general practitioners' attitudes to providing genetic services for common diseases, and to estimate the demand from patients for these services, we used a single-page postal questionnaire survey of all 359 general practitioners registered with the Oxfordshire Health Authority; 339 (94%) responded. These physicians reported that a mean 4.1 patients (95% CI, 3.3-4.9) out of every 1,000 consulting them were concerned about their own risk of a common disease associated with a diagnosis in a family member. Half of the general practitioners (95% CI, 45-56%) counseled about genetics in the last year. A majority of general practitioners accept the need to provide genetic services, but far fewer are competent to do so. Although 60% (95% CI, 55-65%) believed they should be involved with genetic screening for common diseases, only 29% (95% CI, 24-34%) felt sufficiently prepared to take family histories and draw pedigrees, and only 15% (95% CI, 11-19%) felt sufficiently prepared to counsel patients about their genetic test results. Given the necessary training and information, 63% (95% CI, 58-68%) and 64% (95% CI, 59 69%) were willing to provide these services. Even with training and information, not all would be willing to provide these services, and lack of time may be a major deterrent. "Practice-enabling" strategies, such as computerized aids in genetics, may be useful. PMID- 26142377 TI - Genetic Library. PMID- 26142378 TI - Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing. AB - Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient's 12-lead ECG. During a mean 15.6 years (range 3.3 30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 +/- 13.5 vs. 175.7 +/- 14.7 ms in non PHF patients, p < 0.001) and a higher myocardial scar score (5.2 +/- 1.9 vs. 2.7 +/- 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22 2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15-2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03-1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01-1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd >=185 ms and/or myocardial scar score >=4 might be independent long-term prognostic markers of PHF. PMID- 26142380 TI - Editorial Notes. PMID- 26142381 TI - How to Write a Research Article for the Journal of Genetic Counseling. AB - The purpose of this paper is to provide guidance to contributors to the Journal of Genetic Counseling about preparing manuscripts that report findings of original research. While variations in reporting formats and standards are acknowledged, the paper aims to assist contributors in recognizing the essential components of research studies and of manuscripts describing such studies. A description of the purpose of each section and guidelines for writing each section are provided. Criteria for assessing the strengths and weaknesses of study design, sampling, measures, procedures, and data analyses are also discussed. PMID- 26142379 TI - Intramyocardial delivery of VEGF165 via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction. AB - Vascular endothelial growth factor (VEGF), an independent mitogen, has been reported to induce angiogenesis and thus attenuates the damage induced by myocardial infarction (MI). VEGF165 is the most abundant and predominant isoform of VEGF. This study investigates whether this effect could be strengthened by local intramyocardial injection of VEGF165 along with a novel biodegradable Dex PCL-HEMA/PNIPAAm hydrogel and ascertains its possible mechanism of action. Rat models of myocardial infarction were induced by coronary artery ligation. Phosphate-buffered saline (PBS group), Dex-PCL-HEMA/PNIPAAm hydrogel (Gel group), phosphate-buffered saline containing VEGF165 (VP group), and hydrogel containing VEGF165 (VPG group) were injected into a peri-infarcted area of cardiac tissue immediately after myocardial infarction, respectively. The sham group was thoracic but without myocardial infarction. The injection of VEGF165 along with a hydrogel induced angiogenesis, reduced collagen content and MI area, inhibited cell apoptosis, increased the level of VEGF165 protein and the expression of flk 1 and flt-1, and improved cardiac function compared with the injection of either alone after MI in rats. The results suggest that injection of VEGF165 along with a hydrogel acquires more cardioprotective effects than either alone in rat with MI by sustained release of VEGF165, then may enhance the feedback between VEGF and its receptors flk-1 and flt-1. PMID- 26142382 TI - A Survey of Clinical Supervision in Genetic Counseling. AB - Three hundred and thirty-five full members of the National Society of Genetic Counselors completed a survey concerning the nature of clinical supervision for genetic counseling students. Slightly over half (54.3%, n = 182) had provided clinical supervision within the past 5 years. Of those who supervised, 66.7% had 5 years or less supervision experience, and 55% had supervised 10 or fewer students. The majority became supervisors because they enjoy teaching and contributing to the profession. Common reasons for not supervising include no local graduate program, and had never been asked to supervise. Live supervision is the most prevalent student evaluation method: every supervisor reported providing one-on-one oral feedback, and 47.3% indicated that they always provide feedback immediately following a counseling session. The most frequent challenges involve students who lack technical knowledge and who fail to incorporate feedback. Training, policy, and research implications are discussed. PMID- 26142383 TI - What Predicts the Use of Genetic Counseling Services After the Birth of a Child with Down Syndrome? AB - In the state of Victoria, Australia, a government funded genetic counseling service exists to meet the needs of families. An audit showed that many families do not use this service after the birth of a child with a genetic problem. To investigate this we surveyed families of children born with Down syndrome over 2 years in Victoria. Questionnaires were completed by 74 mothers, of whom only 18 had received genetic counseling between the birth and the time of the study (mean 3.5 years). Of those not receiving genetic counseling, 71% said they were not offered or had not heard of it. Mothers who had genetic counseling were younger than those who had not, and were more likely to have attended University. Those who had genetic counseling indicated less "satisfaction with care at the diagnosis" and were more likely to perceive their child as "unwell at birth" than those who were aware of genetic counseling but did not have it. Of those who did not have genetic counseling, over half were unclear about what it is, although 74% agreed with the statement "genetic counseling is most useful when planning to have another child." Of those who had heard of genetic counseling, 73% said they were not sure how it could help. Many families with children with Down syndrome are not aware of the existence or functions of genetic counseling. With greater awareness, some may still choose not to have genetic counseling, but others enunciated needs that could be met by this service if it were offered to them. PMID- 26142384 TI - The Unmet Information and Support Needs of Women with a Family History of Breast Cancer: A Descriptive Survey. AB - This study aims to survey the unmet support needs of women at increased risk of developing breast cancer. In total, 173 unaffected women with a family history of breast cancer completed a 28-item purposely-designed mailed survey. The majority of participants did not report a high level of unmet need for support. Receiving further information about cancer genetics was the most commonly reported area of unmet need. Only about 20% of participants reported a moderate to high degree of interest in attending a hypothetical support group. However, a higher degree of interest was expressed in internet-based information and supportive interventions. Amongst those interested in attending a support group, discussion, and receiving further information were the most preferred activities. Higher levels of unmet support needs were significantly associated with interest in attending groups. No demographic variables were found to predict interest in attending a support group. Implications for those considering establishing support groups are discussed. PMID- 26142385 TI - Microbial lipid production by oleaginous Rhodococci cultured in lignocellulosic autohydrolysates. AB - Metabolic synthesis of single cell oils (SCOs) for biodiesel application by heterotrophic oleaginous microorganisms is being hampered by the high cost of culture media. This study investigated the possibility of using loblolly pine and sweetgum autohydrolysates as economic feedstocks for microbial lipid production by oleaginous Rhodococcus opacus (R. opacus) PD630 and DSM 1069. Results revealed that when the substrates were detoxified by the removal of inhibitors (such as HMF-hydroxymethyl-furfural), the two strains exhibited viable growth patterns after a short adaptation/lag phase. R. opacus PD630 accumulated as much as 28.6 % of its cell dry weight (CDW) in lipids while growing on detoxified sweetgum autohydrolysate (DSAH) that translates to 0.25 g/l lipid yield. The accumulation of SCOs reached the level of oleagenicity in DSM 1069 cells (28.3 % of CDW) as well, while being cultured on detoxified pine autohydrolysate (DPAH), with the maximum lipid yield of 0.31 g/l. The composition of the obtained microbial oils varied depending on the substrates provided. These results indicate that lignocellulosic autohydrolysates can be used as low-cost fermentation substrates for microbial lipid production by wild-type R. opacus species. Consequently, the variety of applications for aqueous liquors from lignocellulosic pretreatment has been expanded, allowing for the further optimization of the integrated biorefinery. PMID- 26142386 TI - Improved PCR assay for the species-specific identification and quantitation of Legionella pneumophila in water. AB - Legionellosis outbreak is a major global health care problem. However, current Legionella risk assessments may be compromised by uncertainties in Legionella detection methods, infectious dose, and strain infectivity. These limitations may place public health at significant risk, leading to significant monetary losses in health care. However, there are still unmet needs for its rapid identification and monitoring of legionellae in water systems. Therefore, in the present study, a primer set was designed based on a LysR-type transcriptional regulator (LTTR) family protein gene of Legionella pneumophila subsp. pneumophila str. Philadelphia 1 because it was found that this gene is structurally diverse among species through BLAST searches. The specificity of the primer set was evaluated using genomic DNA from 6 strains of L. pneumophila, 5 type strains of other related Legionella species, and other 29 reference pathogenic bacteria. The primer set used in the PCR assay amplified a 264-bp product for only targeted six strains of L. pneumophila. The assay was also able to detect at least 1.39 * 10(3) copies/MUl of cloned amplified target DNA using purified DNA or 7.4 * 10(0) colony-forming unit per reaction when using calibrated cell suspension. In addition, the sensitivity and specificity of this assay were confirmed by successful detection of Legionella pneumophila in environmental water samples. PMID- 26142387 TI - Adaptation and tolerance of bacteria against acetic acid. AB - Acetic acid is a weak organic acid exerting a toxic effect to most microorganisms at concentrations as low as 0.5 wt%. This toxic effect results mostly from acetic acid dissociation inside microbial cells, causing a decrease of intracellular pH and metabolic disturbance by the anion, among other deleterious effects. These microbial inhibition mechanisms enable acetic acid to be used as a preservative, although its usefulness is limited by the emergence of highly tolerant spoilage strains. Several biotechnological processes are also inhibited by the accumulation of acetic acid in the growth medium including production of bioethanol from lignocellulosics, wine making, and microbe-based production of acetic acid itself. To design better preservation strategies based on acetic acid and to improve the robustness of industrial biotechnological processes limited by this acid's toxicity, it is essential to deepen the understanding of the underlying toxicity mechanisms. In this sense, adaptive responses that improve tolerance to acetic acid have been well studied in Escherichia coli and Saccharomyces cerevisiae. Strains highly tolerant to acetic acid, either isolated from natural environments or specifically engineered for this effect, represent a unique reservoir of information that could increase our understanding of acetic acid tolerance and contribute to the design of additional tolerance mechanisms. In this article, the mechanisms underlying the acetic acid tolerance exhibited by several bacterial strains are reviewed, with emphasis on the knowledge gathered in acetic acid bacteria and E. coli. A comparison of how these bacterial adaptive responses to acetic acid stress fit to those described in the yeast Saccharomyces cerevisiae is also performed. A systematic comparison of the similarities and dissimilarities of the ways by which different microbial systems surpass the deleterious effects of acetic acid toxicity has not been performed so far, although such exchange of knowledge can open the door to the design of novel approaches aiming the development of acetic acid-tolerant strains with increased industrial robustness in a synthetic biology perspective. PMID- 26142388 TI - Probiotic Saccharomyces cerevisiae strains as biotherapeutic tools: is there room for improvement? AB - The probiotic yeast Saccharomyces cerevisiae var boulardii is widely used as a low cost and efficient adjuvant against gastrointestinal tract disorders such as inflammatory bowel disease and treatment of several types of diarrhea, both in humans and animals. S. boulardii exerts its protective mechanisms by binding and neutralizing enteric pathogens or their toxins, by reducing inflammation and by inducing the secretion of sIgA. Although several S. cerevisiae strains have proven probiotic potential in both humans and animals, only S. boulardii is currently licensed for use in humans. Recently, some researchers started using S. boulardii as heterologous protein expression systems. Combined with their probiotic activity, the use of these strains as prophylactic and therapeutic proteins carriers might result in a positive combined effort to fight specific diseases. Here, we provide an overview of the current use of S. cerevisiae strains as probiotics and their mechanisms of action. We also discuss their potential to produce molecules with biotherapeutic application and the advantages and hurdles of this approach. Finally, we suggest future directions and alternatives for which the combined effort of specific immunomodulatory effects of probiotic S. cerevisiae strains and ability to express desired foreign genes would find a practical application. PMID- 26142389 TI - Methanotrophic community abundance and composition in plateau soils with different plant species and plantation ways. AB - Aerobic methane-oxidizing bacteria (MOB) play an important role in mitigating the methane emission in soil ecosystems to the atmosphere. However, the impact of plant species and plantation ways on the distribution of MOB remains unclear. The present study investigated MOB abundance and structure in plateau soils with different plant species and plantation ways (natural and managed). Soils were collected from unmanaged wild grassland and naturally forested sites, and managed farmland and afforested sites. A large variation in MOB abundance and structure was found in these studied soils. In addition, both type I MOB (Methylocaldum) and type II MOB (Methylocystis) were detected in these soils, while type II MOB usually outnumbered type I MOB. The distribution of soil MOB community was found to be collectively regulated by plantation way, plant species, the altitude of sampling site, and soil properties. PMID- 26142390 TI - Differential modulation of avian beta-defensin and Toll-like receptor expression in chickens infected with infectious bronchitis virus. AB - The host innate immune response either clears invading viruses or allows the adaptive immune system to establish an effective antiviral response. In this study, both pathogenic (passage 3, P3) and attenuated (P110) infectious bronchitis virus (IBV) strains were used to study the immune responses of chicken to IBV infection. Expression of avian beta-defensins (AvBDs) and Toll-like receptors (TLRs) in 16 tissues of chicken were compared at 7 days PI. The results showed that P3 infection upregulated the expression of AvBDs, including AvBD2, 4, 5, 6, 9, and 12, while P110 infection downregulated the expression of AvBDs, including AvBD3, 4, 5, 6, and 9 in most tissues. Meanwhile, the expression level of several TLRs showed a general trend of upregulation in the tissues of P3 infected chickens, while they were downregulated in the tissues of P110-infected chickens. The result suggested that compared with the P110 strain, the P3 strain induced a more pronounced host innate immune response. Furthermore, we observed that recombinant AvBDs (including 2, 6, and 12) demonstrated obvious anti-viral activity against IBV in vitro. Our findings contribute to the proposal that IBV infection induces an increase in the messenger RNA (mRNA) expression of some AvBDs and TLRs, which suggests that AvBDs may play significant roles in the resistance of chickens to IBV replication. PMID- 26142391 TI - Warfarin-related recurrent knee haemarthrosis treated with arterial embolisation and intra-articular injection of tranexamic acid. AB - Haemarthrosis is an uncommon complication of anticoagulation therapy. Tranexamic acid (TXA) has a high clinical value for the treatment of bleeding due to fibrinolysis. We describe a case of a 61-year-old woman with a mechanical heart valve who presented with warfarin-related recurrent haemarthrosis of her right knee, which recurred after transarterial embolisation. Intra-articular injection of TXA led to a cessation of haemarthrosis without any adverse event for 1 year. Intra-articular injection of TXA may be an effective treatment for warfarin related haemarthrosis. PMID- 26142392 TI - Giant acrochordon of the axilla. AB - Acrochordons or fibroepithelial polyps, are very common skin lesions. However, giant acrochordons are extremely rare. We present a case of a morbidly obese diabetic man who was treated with primary excision of a giant 18 cm acrochordon of the left axilla. PMID- 26142393 TI - Pneumomediastinum and pneumoperitoneum caused by tracheostomy displacement. PMID- 26142394 TI - Expression of Na+/H+ exchanger regulatory factor 1 in autosomal-dominant polycystic kidney disease. AB - OBJECTIVE: To explore the role of Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) in autosomal-dominant polycystic kidney disease (ADPKD). METHODS: NHERF1 and beta-catenin protein were detected by immunohistochemistry and Western blotting of kidney tissue samples from patients with ADPKD and controls (normal kidney tissue [>5 cm from the foci] collected from patients undergoing unilateral nephrectomy for kidney cancer). NHERF1 and beta-catenin protein and mRNA were quantified by Western blot and real-time fluorescent quantitative polymerase chain reaction, respectively, in kidney tissue samples from Han:SPRD (+/+) and (cy/+) rats. The effects of human recombinant NHERF1 on proliferation and cell cycle of ADPKD cyst-lining epithelial cells (WT9-12) were evaluated by MTT assay and flow cytometry, respectively. RESULTS: Levels of NHERF1 protein and mRNA were significantly lower, and beta-catenin levels significantly higher, in patients with ADPKD and Han:SPRD (cy/+) rats, compared with control subjects and (+/+) rats, respectively. Exogenous recombinant NHERF1 significantly inhibited proliferation of WT9-12 cells and increased the proportion of cells in G(0)/G(1) phase. CONCLUSIONS: ADPKD is associated with a decrease in NHERF1 protein and mRNA levels. Supplementing exogenous NHERF1 inhibited the proliferation of WT9-12 cells. PMID- 26142395 TI - Hyperfiltration in Indigenous Australians with and without diabetes. AB - BACKGROUND: Hyperfiltration (HF) has been linked to the development of diabetic kidney disease (DKD), but the causative or predictive role of HF in the pathogenesis of DKD still remains unclear. To date, there have been no studies of HF in Indigenous Australians, a population with high rates of both diabetes and end-stage kidney disease. We aimed to compare the characteristics and frequency of HF in Indigenous Australians with and without type 2 diabetes. METHODS: Indigenous Australian participants, recruited across five pre-defined strata of health, diabetes status and kidney function, had a reference glomerular filtration rate (GFR) measured using plasma disappearance of iohexol [measured GFR(mGFR)] over 4 h. HF was defined in various ways: (i) mGFR > 144 mL/min/1.73 m(2), which is mGFR > 1.96 * SD above the mean of the mGFR in non-diabetic participants with normal albuminuria and normal renal function (mGFR > 90 mL/min/1.73 m(2)); (ii) age-corrected mGFR (>144 mL/min/1.73 m(2)) to account for the effect of ageing on GFR in subjects over 40 years of age with cut-off 1 mL/min/1.73 m(2) lower for every year; (iii) mGFR > 144 mL/min, without correction for body surface area or age, as well as (iv) mGFR > 125 mL/min/1.73 m(2), without adjustment for age. RESULTS: A total of 383 Indigenous participants, 125 with and 258 without diabetes, with mGFR > 90 mL/min/1.73 m(2) were studied. The proportion of participants with HF was 7% using mGFR > 144 mL/min/1.73 m(2), 11% using the age-adjusted definition, 19% using mGFR > 144 mL/min and 27% using mGFR > 125 mL/min/1.73 m(2). Diabetes was more common in participants with HF (40-74%) compared with normofiltering participants (28-31%), regardless of the definition of HF. CONCLUSIONS: HF exists in Indigenous Australians with and without diabetes. A greater proportion of participants had diabetes in HF group compared with normofiltration group. Long-term follow-up of this cohort is necessary to determine if HF plays a role in the development of DKD and non-DKD. PMID- 26142396 TI - Novel iron-containing phosphate binders and anemia treatment in CKD: oral iron intake revisited. AB - Recent reports have shown that novel phosphate binders containing iron are not only efficacious for the treatment of hyperphosphatemia but also may reduce the need for erythropoiesis-stimulating agents and intravenous (IV) iron for anemia management in patients on maintenance hemodialysis (MHD). Possible healthcare cost savings, which have not been demonstrated in a long-term study, may be an additional advantage of using such multi-pronged treatment strategies for the control of both hyperphosphatemia and iron needs. It is currently assumed that oral iron supplementation is less efficient than the IV route in patients with chronic kidney disease (CKD). The unexpected efficacy of novel iron-containing phosphate binders, such as ferric citrate, in repleting insufficient iron stores and improving the anemia of CKD could change this view. Previous assumptions of self-controlled iron uptake by 'mucosal block' or hepcidin, or else by impaired intestinal iron absorption due to CKD-associated inflammation cannot be reconciled with recent observations of the effects of ferric citrate administration. Citrate in the intestinal lumen may partly contribute to the acceleration of iron absorption. Animal experiments and clinical studies have also shown that oral iron overload can cause excessive iron accumulation despite high hepcidin levels, which are not able to block iron absorption completely. However, like with IV iron agents, no long-term safety data exist with respect to the effects of iron-containing phosphate binders on 'hard' patient outcomes. Future randomized prospective studies in patients with CKD are necessary to establish the safety of oral iron-containing phosphate binders for the control of both hyperphosphatemia and renal anemia. PMID- 26142397 TI - Hydrogen sulfide accelerates the recovery of kidney tubules after renal ischemia/reperfusion injury. AB - BACKGROUND: Progression of acute kidney injury to chronic kidney disease (CKD) is associated with inadequate recovery of damaged kidney. Hydrogen sulfide (H2S) regulates a variety of cellular signals involved in cell death, differentiation and proliferation. This study aimed to identify the role of H2S and its producing enzymes in the recovery of kidney following ischemia/reperfusion (I/R) injury. METHODS: Mice were subjected to 30 min of bilateral renal ischemia. Some mice were administered daily NaHS, an H2S donor, and propargylglycine (PAG), an inhibitor of the H2S-producing enzyme cystathionine gamma-lyase (CSE), during the recovery phase. Cell proliferation was assessed via 5'-bromo-2'-deoxyuridine (BrdU) incorporation assay. RESULTS: Ischemia resulted in decreases in CSE and cystathionine beta-synthase (CBS) expression and activity, and H2S level in the kidney. These decreases did not return to sham level until 8 days after ischemia when kidney had fibrotic lesions. NaHS administration to I/R-injured mice accelerated the recovery of renal function and tubule morphology, whereas PAG delayed that. Furthermore, PAG increased mortality after ischemia. NaHS administration to I/R-injured mice accelerated tubular cell proliferation, whereas it inhibited interstitial cell proliferation. In addition, NaHS treatment reduced post-I/R superoxide formation, lipid peroxidation, level of GSSG/GSH and Nox4 expression, whereas it increased catalase and MnSOD expression. CONCLUSIONS: Our findings demonstrate that H2S accelerates the recovery of I/R-induced kidney damage, suggesting that the H2S-producing transsulfuration pathway plays an important role in kidney repair after acute injury. PMID- 26142398 TI - Spontaneous remission of proteinuria is a frequent event in phospholipase A2 receptor antibody-negative patients with membranous nephropathy. AB - BACKGROUND: Phospholipase A2 receptor antibodies (PLA2R-Ab) and thrombospondin type-1 domain-containing 7A antibodies (THSD7A-Ab) are present in 70-80% of patients with membranous nephropathy (MN). Little, however, is known about the pathogenesis of MN and the clinical outcome in PLA2R-Ab- and THSD7A-Ab-negative patients. METHODS: In this prospective multicentre observational study, the clinical outcome of 37 patients with biopsy-proven MN who were negative for PLA2R Ab and THSD7A-Ab in the serum was analysed. RESULTS: A total of 198 patients were screened for inclusion in the study. Of these, 157 patients were positive for PLA2R-Ab and 4 patients for THSD7A-Ab. The remaining 37 patients were negative for both antibodies were and included in this study. Six patients died during the follow-up, five because of malignant diseases and one of an infection. One patient went into end-stage renal disease, and two patients were lost to follow up. The remaining 28 patients were followed for at least 24 months (35.6 +/- 8.9 months). Seventeen patients received immunosuppressive (IS) therapy, and 11 received supportive care only. At the end of the follow-up, 14 of the 17 patients treated with immunosuppressants and 10 of 11 patients on supportive therapy had a remission of proteinuria. The time to reach remission of proteinuria and serum creatinine levels at the end of the follow-up were not different between both groups. A univariate Cox regression analysis indicated that the use of immunosuppression did not alter the chance to reach a remission of proteinuria. CONCLUSIONS: A high number of PLA2R-Ab- and THSD7A-Ab-negative patients with MN have a good prognosis and might not need IS therapy. PMID- 26142399 TI - [Pertinence of Off-label Prescriptions of Innovating and Expensive Drugs in a University Hospital]. AB - OBJECTIVES: Pertinence of off-label prescriptions of innovative and expensive drugs needs a strict scientific appraisal to prevent adverse reaction risks and financial drift. METHODS: Pertinence of such prescriptions has been analyzed in a University Hospital by bibliometric methods. Scientific publications issued from this clinical activity have been also evaluated. RESULTS: Oncology differed from other clinical specialties by a better pertinence in justifying off-label prescriptions (good evidence level in 46% vs. 21%, scientific publications issued from A/B ranked journals: 51% versus 41%). Quality of scientific production from oncologists was also better (publication impact factor [IF] mean: 4.571 versus 2.245). CONCLUSIONS: The better pertinence of off-label prescriptions by oncologists in comparison to others clinicians' ones was mainly due to a shorter field of indications but also to a more efficient organisation such as systematic prescription by seniors, dedicated computerized provider order entry, multidisciplinary team meetings and collaborative culture. PMID- 26142400 TI - Indoleamine 2,3-dioxygenase 1 in corneal endothelial cells limits herpes simplex virus type 1-induced acquired immune response. AB - BACKGROUND: Corneal endothelial cells are known to be targets of herpes simplex virus type 1 (HSV-1) infection; however, the pathogenesis of HSV infections of the endothelial cells has not been definitively determined. The purpose of this study was to examine an unrecognised strategy of corneal endothelial cells to protect themselves from HSV-1 infection. METHODS: Immortalised human corneal endothelial cells (HCEn) were infected with HSV-1. Based on the global transcriptional profile, the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was determined using real-time PCR and western blots. To examine whether IDO1 has any antiviral role, we tested whether viral replication was affected by blocking the activity of IDO1. The immune modulatory role of IDO1 was analysed to determine whether IDO1 might contribute to modulating the recall responses of HSV 1-sensitised CD4(+) T cells. RESULTS: IDO1 was strongly expressed in HCEn cells after HSV-1 infection. IDO1 blockade did not significantly restrict viral transcription or replication, arguing against a previously recognised antiviral role for IDO1. When HCEn cells were examined for antigen-presenting function, HSV 1-primed HCEn cells stimulated the proliferation of allogeneic CD4(+) T cells and interleukin 10 (IL-10) secretion. When the recall response to HSV-1 was measured by the mixed lymphocyte reaction, the HCEn-stimulated CD4(+) T cells modulated and limited the recall response. When IDO1 was silenced in HCEn cells, the HCEn mediated immune modulatory activity and regulatory T-cell activation were reduced. Overexpression of IDO1 promoted immune modulatory activity, which was partly conveyed by IL-10. CONCLUSIONS: IDO1 induced by HSV-1 infection limits and dampens excessive acquired immune responses in corneal endothelial cells. PMID- 26142401 TI - The Royal College of Ophthalmologists' National Ophthalmology Database Study of vitreoretinal surgery: report 5, anaesthetic techniques. AB - AIMS: To explore trends over time and variation in the use of anaesthetic techniques for vitreoretinal (VR) surgery in the UK. METHODS: Prospectively collected data from 13 centres contributing >50 VR operations, including either pars plana vitrectomy (PPV) or scleral buckle (SB), between May 2000 and November 2010 were retrospectively analysed. Anaesthesia was categorised as general anaesthesia (GA) or local anaesthesia (LA) and results were reported by year, centre, grade of surgeon and type of operation. RESULTS: 160 surgeons performed 12 124 operations on 10 405 eyes (9935 patients); 6054 (49.9%) under GA and 6070 (50.1%) under LA. The percentage performed under GA decreased from 95.3% in 2001 to 40.9% in 2010. Within LA techniques, peribulbar or retrobulbar injection was used in 2783 (45.8%) operations and sub-Tenon's cannula in 3287 (54.2%). The proportions of operations performed under GA or LA were similar for consultants and trainees. Primary SB, primary combined PPV and SB for retinal detachment (RD), repeat RD surgery and complex vitrectomy surgery were more commonly performed under GA (85.8%, 67.0%, 63.5% and 69.4%, respectively), while primary PPV for RD, simple vitrectomy surgery and macular surgery were more commonly performed under LA (58.1%, 53.7% and 58.2%, respectively). Marked intercentre variation existed with the extremes being one centre with 100% of operations performed under GA and one centre with 98.3% under LA. CONCLUSIONS: LA for VR surgery has steadily increased over the last decade in the UK but marked intercentre variation exists. PMID- 26142403 TI - Structural neighbourhood conditions, social cohesion and psychological distress in the Netherlands. AB - BACKGROUND: Neighbourhood inequalities in psychological distress are well reported, but underlying mechanisms remain poorly understood. The main purposes of this study were to investigate associations between structural neighbourhood conditions and psychological distress, and to explore the potential mediating role of neighbourhood social cohesion. METHODS: Cross-sectional questionnaire study on a random sample of 18,173 residents aged >= 16 years (response 49%) from the four largest cities in the Netherlands. Psychological distress was measured with the Kessler Psychological Distress Scale (K10). Structural environmental factors under study were neighbourhood socio-economic status (SES), neighbourhood green, urbanity and home maintenance. Neighbourhood social cohesion was measured by five statements and aggregated to the neighbourhood level by using ecometrics methodology. Multilevel linear regression analysis was used to investigate associations of neighbourhoods characteristics with psychological distress, adjusted for individual level characteristics. RESULTS: High neighbourhood SES and neighbourhood social cohesion were associated with decreased psychological distress. Adjusted for individual level characteristics and neighbourhood SES, only neighbourhood social cohesion remained significantly associated with psychological distress. Neighbourhood social cohesion accounted for 38% of the differences in the association between neighbourhood SES and psychological distress. CONCLUSIONS: High neighbourhood social cohesion is significantly associated with decreased psychological distress among residents of the four largest cities in the Netherlands. Reducing neighbourhood inequalities in psychological distress may require increasing social interactions among neighbourhood residents. PMID- 26142404 TI - Nursing contribution to the achievement of prioritized objectives in primary health care: a cross-sectional study. AB - BACKGROUND: Concern for the sustainability of health care systems has forced health authorities and insurance companies to develop performance measurement systems to promote the achievement of health objectives. These actions aim to stimulate quality improvement while controlling costs by making providers accountable for what they do as well as for the quality of the care they provide. However, the extent to which each professional contributes to the achievement of the health objectives is largely unknown. The aim of this study was to analyse the contribution of nurses to achieving the objectives for primary health care (PHC) services prioritized by the public insurer. METHODS: A cross-sectional study was conducted using data from the PHC services of the public healthcare network in Catalonia, Spain, during the period 2006-09. Indicators linked to the prioritized health objectives were classified as nursing sensitive and non nursing sensitive using criteria defined by international institutions. A multilevel linear regression model was applied to evaluate the temporal evolution of the two sets of indicators. RESULTS: Specifically, 39.4% of the indicators linked to the health objectives were nursing sensitive. The evolution of the indicators showed an improvement in the achievement of most of the prioritized objectives. Although this improvement was greater for nursing-sensitive indicator outcomes, the difference did not reach statistical significance (P = 0.09). CONCLUSION: Nursing has a relevant role in the achievement of a significant number of health objectives in PHC services. This contribution should be recognized as it has important consequences in terms of service payment and public health. PMID- 26142402 TI - Ambient air pollution and racial/ethnic differences in carotid intima-media thickness in the Multi-Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: In the USA, ethnic disparities in atherosclerosis persist after accounting for known risk factors. Ambient air pollution is associated with increased levels of atherosclerosis and differs in the USA by race/ethnicity. We estimated the influence of ambient air pollution exposure to ethnic differences in common carotid intima-media thickness (IMT). METHODS: We cross-sectionally studied 6347 Caucasian-American, African-American, Hispanic and Chinese adults across 6 US cities in 2000-2002. Annual ambient air pollution concentrations (fine particulate matter [PM2.5] and oxides of nitrogen [NOX]) were estimated at each participant's residence. IMT was assessed by ultrasound. RESULTS: The mean IMT was 19.4 and 37.6 MUm smaller for Hispanic women and men, 53.6 and 7.1 MUm smaller for Chinese women and men, and 23.4 and 38.7 MUm higher for African American women and men compared with Caucasian-American women and men. After adjustment for PM2.5, the differences in IMT remained similar for Hispanic and African-American participants but was even more negative for Chinese participants (mean IMT difference of -58.4 MUm for women and -15.7 MUm for men) compared with Caucasian-American participants. The IMT difference in Chinese participants compared with Caucasian-American participants related to their higher PM2.5 exposures was 4.8 MUm (95% CI 0.2 to 10.8) for women and 8.6 MUm (95% CI 3.4 to 15.3) for men. NOX was not related to ethnic differences in IMT. CONCLUSIONS: The smaller carotid IMT levels in Chinese participants were even smaller after accounting for higher PM2.5 concentrations in Chinese participants compared with Caucasian-American participants. Air pollution was not related to IMT differences in African-American and Hispanic participants compared with Caucasian-American participants. PMID- 26142405 TI - The relationship between intensity and duration of physical activity and subjective well-being. AB - AIM: Previous research documented a positive effect of physical activity on subjective well-being (SWB). Yet, mainly broad activity measures (e.g. resulting from yes-no questions) were used and the effect of different participation intensities and durations has been largely neglected. The aim of this study is to examine the effect of physical activity on SWB by focusing on participation intensity and duration. METHODS: Survey data from 28 European countries are used for the analysis (n = 22 971). Two regression models (Generalized Method of Moments) are estimated which analyze the effect of participation intensity and duration on SWB (measured by life satisfaction). Given the endogeneity of the participation measures, instrumental variables are used (sport opportunities, club membership, time spent sitting). The models also control for other factors that could affect SWB (e.g. age, occupation). RESULTS: The results for participation intensity show that the number of days people practised at moderate intensity in the week prior to the interview have a significant and positive effect on SWB, while the number of days with vigorous-intensity activity has a significant and negative impact. Similarly, the models for duration indicate that the minutes spent on moderate-intensity activity significantly add to SWB, while the minutes spent on vigorous-intensity activity significantly reduce the level of SWB. CONCLUSIONS: The findings challenge the World Health Organization's recommendation in the sense that activity at moderate and vigorous intensity is not interchangeable if the aim is to also improve SWB (and not only physical health). PMID- 26142406 TI - A qualitative investigation of the role of the family in structuring young people's alcohol use. AB - BACKGROUND: Few qualitative studies have investigated young people's perspectives around influences on substance use. We aimed to examine young people's understandings, attitudes and experiences around alcohol, tobacco and cannabis use and factors influencing substance use behaviour. METHODS: Qualitative interview study involving 28 young people (13 males and 15 females) aged 18-20 years, recruited purposively on the basis of substance use, who were participating in the Avon Longitudinal Study of Parents and Children. Interviews were conducted at participants' homes or at local cafes. Audio data were transcribed verbatim, systematically coded and analysed inductively using a constant comparative approach. RESULTS: Parental attitudes and behaviours and the nature of communication emerged as critical factors structuring young people's alcohol use. Initiation of alcohol use was frequently mediated by parents early in adolescence, with the home recounted as a primary site of early drinking experiences. Later in adolescence, young people perceived a more permissive stance towards alcohol use, with broad acceptance of high levels of consumption and recognition of drinking as a cultural norm during adolescence. In contrast, young people reported a more prohibitive and discouraging stance from their parents towards tobacco and cannabis use, and the use of these substances appeared to be of greater parental concern. CONCLUSIONS: Interventions involving parents or guardians have a critical role to play in the prevention of harms arising from alcohol use during adolescence. However, such interventions are needed in conjunction with individual, school, community and environmental interventions to shift cultural norms across the population and to facilitate effective prevention. PMID- 26142407 TI - Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. AB - Mupirocin 2% ointment is used either alone or with skin antiseptics as part of a comprehensive MRSA decolonization strategy. Increased mupirocin use predisposes to mupirocin resistance, which is significantly associated with persistent MRSA carriage. Mupirocin resistance as high as 81% has been reported. There is a strong association between previous mupirocin exposure and both low-level and high-level mupirocin resistance. High-level mupirocin resistance (mupA carriage) is also linked to MDR. Among MRSA isolates, the presence of the qacA and/or qacB gene, encoding resistance to chlorhexidine, ranges from 65% to 91%, which, along with mupirocin resistance, is associated with failed decolonization. This is of significant concern for patient care and infection prevention and control strategies as both these agents are used concurrently for decolonization. Increasing bacterial resistance necessitates the discovery or development of new antimicrobial therapies. These include, for example, polyhexanide, lysostaphin, ethanol, omiganan pentahydrochloride, tea tree oil, probiotics, bacteriophages and honey. However, few of these have been evaluated fully or extensively tested in clinical trials and this is required to in part address the implications of mupirocin resistance. PMID- 26142408 TI - Lack of cross-toxicity between isoniazid and ethionamide in severe cutaneous adverse drug reactions: a series of 25 consecutive confirmed cases. AB - BACKGROUND: Isoniazid and ethionamide are important first- and second-line anti TB drugs (FLDs and SLDs), respectively. Ethionamide is a structural analogue of isoniazid and the two drugs share other similarities, including their metabolism, therapeutic targets, hepato-toxicity patterns and drug resistance. As a result, there has always been concern about possible cross-reactivity between them. METHODS: Among 69 patients with drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) to FLDs, FLDs were stopped and SLDs added when the skin and laboratory parameters had settled. This was followed by sequential and additive rechallenge with FLDs. We report 25 consecutive cases that developed confirmed cutaneous adverse drug reactions (CADRs) to isoniazid or ethionamide used as FLD and SLD, respectively. RESULTS: Sixty-nine participants who developed CADRs on FLDs were enrolled in the study. Twenty developed a rechallenge reaction to isoniazid and five reacted to ethionamide. Four of the 20 isoniazid cases were patch test positive, 3/20 were skin prick test positive and 13/20 reacted to oral rechallenge. All seven cases that were patch and skin prick test positive were associated with systemic reactions. Twenty of the 25 cases had DRESS and 5 had SJS/TEN. Twenty-three of the 25 cases with rechallenge reactions were HIV infected. Importantly, none of the cases that reacted to ethionamide during the rechallenge reacted to isoniazid and none who subsequently reacted to isoniazid reacted to ethionamide. CONCLUSIONS: Our findings strongly suggest that the risk of cross-reactivity of isoniazid and ethionamide in DRESS syndrome and SJS/TEN is low. These findings have implications for clinical management. PMID- 26142409 TI - Is it time to revise linezolid doses in peritoneal dialysis patients? A case series. PMID- 26142410 TI - WGS accurately predicts antimicrobial resistance in Escherichia coli. AB - OBJECTIVES: The objective of this study was to determine the effectiveness of WGS in identifying resistance genotypes of MDR Escherichia coli and whether these correlate with observed phenotypes. METHODS: Seventy-six E. coli strains were isolated from farm cattle and measured for phenotypic resistance to 15 antimicrobials with the Sensititre((r)) system. Isolates with resistance to at least four antimicrobials in three classes were selected for WGS using an Illumina MiSeq. Genotypic analysis was conducted with in-house Perl scripts using BLAST analysis to identify known genes and mutations associated with clinical resistance. RESULTS: Over 30 resistance genes and a number of resistance mutations were identified among the E. coli isolates. Resistance genotypes correlated with 97.8% specificity and 99.6% sensitivity to the identified phenotypes. The majority of discordant results were attributable to the aminoglycoside streptomycin, whereas there was a perfect genotype-phenotype correlation for most antibiotic classes such as tetracyclines, quinolones and phenicols. WGS also revealed information about rare resistance mechanisms, such as structural mutations in chromosomal copies of ampC conferring third-generation cephalosporin resistance. CONCLUSIONS: WGS can provide comprehensive resistance genotypes and is capable of accurately predicting resistance phenotypes, making it a valuable tool for surveillance. Moreover, the data presented here showing the ability to accurately predict resistance suggest that WGS may be used as a screening tool in selecting anti-infective therapy, especially as costs drop and methods improve. PMID- 26142411 TI - Lung herniation in the implantable cardioverter defibrillator pocket. PMID- 26142412 TI - Phenomenology and beliefs of patients with Dhat syndrome: A nationwide multicentric study. AB - AIM: To assess the phenomenology and associated beliefs in patients with Dhat syndrome. METHODS: A total of 780 male patients aged more than 16 years were recruited from 15 centers spread across the country and were assessed on Dhat Syndrome Questionnaire. RESULTS: The most commonly reported reasons for passage of Dhat were excessive masturbation (55.1%), sexual dreams (47.3%), excessive sexual desire (42.8%) and consumption of high energy foods (36.7%). The most common situation in which participants experienced passage of Dhat were as 'night falls' (60.1%) and 'while passing stools' (59.5%). The most common consequence due to passage of Dhat was weakness in sexual ability (75.6%). In terms of psychological and somatic symptoms, the common symptoms included bodily weakness (78.2%); feeling tired or having low energy (75.9%); feeling down, depressed, or hopeless (67.9%); and little interest or pleasure in doing things (63.7%). In terms of treatment expectations, about half of the patients (49.1%) expected that energizing medications like vitamins/tonics/tablets were required and more than one-third (38.2%) expected that there was a need for taking energizing injections. CONCLUSION: Present study shows that Dhat syndrome is a distinct clinical entity seen all over India, with its characteristic features. PMID- 26142414 TI - The role of the pericardium in the valveless, tubular heart of the tunicate Ciona savignyi. AB - Tunicates, small invertebrates within the phylum Chordata, possess a robust tubular heart which pumps blood through their open circulatory systems without the use of valves. This heart consists of two major components: the tubular myocardium, a flexible layer of myocardial cells that actively contracts to drive fluid down the length of the tube; and the pericardium, a stiff, outer layer of cells that surrounds the myocardium and creates a fluid-filled space between the myocardium and the pericardium. We investigated the role of the pericardium through in vivo manipulations on tunicate hearts and computational simulations of the myocardium and pericardium using the immersed boundary method. Experimental manipulations reveal that damage to the pericardium results in aneurysm-like bulging of the myocardium and major reductions in the net blood flow and percentage closure of the heart's lumen during contraction. In addition, varying the pericardium-to-myocardium (PM) diameter ratio by increasing damage severity was positively correlated with peak dye flow in the heart. Computational simulations mirror the results of varying the PM ratio experimentally. Reducing the stiffness of the myocardium in the simulations reduced mean blood flow only for simulations without a pericardium. These results indicate that the pericardium has the ability to functionally increase the stiffness of the myocardium and limit myocardial aneurysms. The pericardium's function is likely to enhance flow through the highly resistive circulatory system by acting as a support structure in the absence of connective tissue within the myocardium. PMID- 26142415 TI - Paul of Aegina (c. 7th Century AD): Introducing in the Surgical Operating Theatre of the Era an Innovative Tonsillectomy With a Forceps Under the Sunlight. PMID- 26142416 TI - Patellar Fractures: An Innovative Surgical Technique With Transosseous Suture to Avoid Implant Removal. AB - PURPOSE: To describe a new surgical procedure and its outcomes: osteosynthesis with high-resistance sutures, avoiding metallic implants. Open sky osteosynthesis with Kirschner and cerclage wiring is the current gold standard for patella fractures. Favorable functional outcomes have been observed, although implant removal is required in many cases due to the prominent wires under the skin. New implants have been sought after to minimize the need for second surgeries. METHODS: Eight patients, aged between 25 and 61 years, with a minimum follow-up of 24 months, were included in the present study. The surgical procedure consists of open reduction followed by internal fixation performing 3 longitudinal tunnels crossing double high-resistance sutures within these tunnels and suturing among them. Next, an anterior cerclage with parenchymal suture was performed. RESULTS: During follow-up, no secondary fracture displacement was observed. No patient required or requested implant removal. Functional outcomes were equitable to other surgical techniques. CONCLUSION: Despite the relatively small number of patients, osteosynthesis with high-resistance suture presents as an acceptable alternative within patella fracture treatment, being safe and with similar functional outcomes when compared with other techniques. Furthermore, no second surgeries for implant removal were required during the present study. PMID- 26142413 TI - The importance of foetal movement for co-ordinated cartilage and bone development in utero : clinical consequences and potential for therapy. AB - Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities. Cite this article: Bone Joint Res 2015;4:105-116. PMID- 26142417 TI - Cold-Plasma Coagulation on the Surface of the Small Bowel Is Safe in Pigs. AB - INTRODUCTION: Surgical treatment in patients with peritoneal carcinomatosis is often limited by the extent of small bowel involvement. We investigated the results of the application of cold-plasma coagulation on the surface of the small bowel. METHODS: After permission by the federal government of Schleswig-Holstein, 8 female pigs underwent a laparoscopy and cold-plasma coagulation on the small bowel with different energy levels. Cold plasma is generated by high-frequency energy that is directed through helium gas. After 12 to 18 days a laparotomy was done and the abdomen was inspected for peritonitis, fistula, or other pathology. RESULTS: Perioperative morbidity was low with transient diarrhea in 1 pig and loss of appetite for 1 day in another pig. We saw 1 interenteric fistula that was clinically not apparent after accidently prolonged application of cold-plasma coagulation (6 seconds instead of 2 seconds) with the highest energy level of 100 W. We did not observe any mortality. The depth of necrosis after application of different energy levels was dependent on the generator energy. We observed statistically significant differences between the different energy levels (20 W vs 10 W [P = .014], 75 W vs 50 W [P = .011]). The comparison of the necrosis depths after the application of 100 W and 75 W almost reached statistical significance (P = .059). We observed distinct interenteric adhesions as a result of the coagulation. DISCUSSION: The application of cold-plasma coagulation on the surface of vital bowel in pigs is safe. We would recommend against the use of the highest energy level of 100 W before more clinical data are available. PMID- 26142418 TI - Relevance to family practice of English-language guidelines on breast, colorectal and prostate cancer: a review. AB - BACKGROUND: GPs regard cancer guidelines as useful yet criticise their limited applicability to the primary care setting. OBJECTIVES: To determine the extent to which English-language breast, colorectal and prostate cancer guidelines contain recommendations that are relevant to GPs and to find out which of the GPs' roles in cancer care the recommendations refer to. METHODS: Evidence- and consent-based English-language breast, colorectal and prostate cancer guidelines were searched for in guideline databases and selected guideline providers' web pages, and checked against inclusion and exclusion criteria. Relevant recommendations were identified, extracted and examined. The involvement of GPs in guideline development as well as whether they were named as a target group was further investigated. RESULTS: Of the 65 identified guidelines, 35 were eligible and contained recommendations applicable to GPs. GPs were directly involved in the development of the majority of only breast cancer guidelines and were explicitly named as a target group in fewer than 50% of guidelines. The majority of recommendations dealt with patient-physician communication, with a focus on cancer therapy. Rarer procedural recommendations predominantly concentrated on follow-up/survivorship care. Less than one-third of all relevant recommendations concerned diagnosis. Only breast cancer guidelines provided a high number of recommendations on transitions between primary and secondary care. CONCLUSION: Greater consideration of GPs would increase their acceptance of guidelines, promote delivery of high-quality cancer care and clarify responsibilities between cancer care providers. The GP's role in cancer diagnosis is not appropriately reflected in cancer guideline recommendations. PMID- 26142420 TI - Odor Emotional Quality Predicts Odor Identification. AB - It is commonly agreed upon a strong link between emotion and olfaction. Odor evoked memories are experienced as more emotional compared with verbal, visual, and tactile stimuli. Moreover, the emotional quality of odor cues increases memory performance, but contrary to this, odors are poor retrieval cues for verbal labels. To examine the relation between the emotional quality of an odor and its likelihood of identification, this study evaluates how normative emotion ratings based on the 3-dimensional affective space model (that includes valence, arousal, and dominance), using the Self-Assessment Manikin by Bradley and Lang (Bradley MM, Lang PJ. 1994. Measuring emotion: the Self-Assessment Manikin and the Semantic Differential. J Behav Ther Exp Psychiatry. 25(1):49-59.) and the Positive and Negative Affect Schedule (Watson D, Clark LA, Tellegen A. 1988. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 54(6):1063-1070.) predict the identification of odors in a multiple choice condition. The best fitting logistic regression model includes squared valence and dominance and thus, points to a significant role of specific emotional features of odors as a main clue for odor identification. PMID- 26142419 TI - Characterization of Rolled and Erect Leaf 1 in regulating leave morphology in rice. AB - Leaf morphology, particularly in crop, is one of the most important agronomic traits because it influences the yield through the manipulation of photosynthetic capacity and transpiration. To understand the regulatory mechanism of leaf morphogenesis, an Oryza sativa dominant mutant, rolled and erect leaf 1 (rel1) has been characterized. This mutant has a predominant rolled leaf, increased leaf angle, and reduced plant height phenotype that results in a reduction in grain yield. Electron microscope observations indicated that the leaf incurvations of rel1 dominant mutants result from the alteration of the size and number of bulliform cells. Molecular cloning revealed that the rel1 dominant mutant phenotype is caused by the activation of the REL1 gene, which encodes a novel unknown protein, despite its high degree of conservation among monocot plants. Moreover, the downregulation of the REL1 gene in the rel1 dominant mutant restored the phenotype of this dominant mutant. Alternatively, overexpression of REL1 in wild-type plants induced a phenotype similar to that of the dominant rel1 mutant, indicating that REL1 plays a positive role in leaf rolling and bending. Consistent with the observed rel1 phenotype, the REL1 gene was predominantly expressed in the meristem of various tissues during plant growth and development. Nevertheless, the responsiveness of both rel1 dominant mutants and REL1 overexpressing plants to exogenous brassinosteroid (BR) was reduced. Moreover, transcript levels of BR response genes in the rel1 dominant mutants and REL1 overexpressing lines were significantly altered. Additionally, seven REL1 interacting proteins were also identified from a yeast two-hybrid screen. Taken together, these findings suggest that REL1 regulates leaf morphology, particularly in leaf rolling and bending, through the coordination of BR signalling transduction. PMID- 26142421 TI - Oleogustus: The Unique Taste of Fat. AB - Considerable mechanistic data indicate there may be a sixth basic taste: fat. However, evidence demonstrating that the sensation of nonesterified fatty acids (NEFA, the proposed stimuli for "fat taste") differs qualitatively from other tastes is lacking. Using perceptual mapping, we demonstrate that medium and long chain NEFA have a taste sensation that is distinct from other basic tastes (sweet, sour, salty, and bitter). Although some overlap was observed between these NEFA and umami taste, this overlap is likely due to unfamiliarity with umami sensations rather than true similarity. Shorter chain fatty acids stimulate a sensation similar to sour, but as chain length increases this sensation changes. Fat taste oral signaling, and the different signals caused by different alkyl chain lengths, may hold implications for food product development, clinical practice, and public health policy. PMID- 26142422 TI - CSER and eMERGE: current and potential state of the display of genetic information in the electronic health record. AB - OBJECTIVE: Clinicians' ability to use and interpret genetic information depends upon how those data are displayed in electronic health records (EHRs). There is a critical need to develop systems to effectively display genetic information in EHRs and augment clinical decision support (CDS). MATERIALS AND METHODS: The National Institutes of Health (NIH)-sponsored Clinical Sequencing Exploratory Research and Electronic Medical Records & Genomics EHR Working Groups conducted a multiphase, iterative process involving working group discussions and 2 surveys in order to determine how genetic and genomic information are currently displayed in EHRs, envision optimal uses for different types of genetic or genomic information, and prioritize areas for EHR improvement. RESULTS: There is substantial heterogeneity in how genetic information enters and is documented in EHR systems. Most institutions indicated that genetic information was displayed in multiple locations in their EHRs. Among surveyed institutions, genetic information enters the EHR through multiple laboratory sources and through clinician notes. For laboratory-based data, the source laboratory was the main determinant of the location of genetic information in the EHR. The highest priority recommendation was to address the need to implement CDS mechanisms and content for decision support for medically actionable genetic information. CONCLUSION: Heterogeneity of genetic information flow and importance of source laboratory, rather than clinical content, as a determinant of information representation are major barriers to using genetic information optimally in patient care. Greater effort to develop interoperable systems to receive and consistently display genetic and/or genomic information and alert clinicians to genomic-dependent improvements to clinical care is recommended. PMID- 26142424 TI - Assessing payer perspectives on health information exchange. AB - OBJECTIVE: To identify factors that impede payer engagement in a health information exchange (HIE), along with organizational and policy strategies that might effectively address the impediments. MATERIALS AND METHODS: Qualitative analysis of semi-structured interviews with leaders from 17 varied payer organizations from across the country (e.g., large, national payers; state Blues plans; local Medicaid managed care plans). RESULTS: We found a large gap between payers' vision of what optimal HIE should be and the current approach to HIE in the United States. Notably, payers sought to be active participants in HIE efforts--both providing claims data and accessing clinical data to support payer HIE use cases. Instead, payers were often asked by HIE efforts only to provide financial support without the option to participate in data exchange, or, when given the option, their data needs were secondary to those of providers. DISCUSSION: Efforts to engage payers in pursuit of more robust and sustainable HIE need to better align their value proposition with payer HIE use cases. This will require addressing provider concerns about payer access to clinical data. Policymakers should focus on creating the conditions for broader payer engagement by removing common obstacles, such as low provider engagement in HIE. CONCLUSION: Despite variation in the extent to which payers engaged with current HIE efforts, there was agreement on the vision of optimal HIE and the facilitators of greater payer engagement. Specific actions by those leading HIE efforts, complemented by policy efforts nationally, could greatly increase payer engagement and enhance HIE sustainability. PMID- 26142423 TI - A system to build distributed multivariate models and manage disparate data sharing policies: implementation in the scalable national network for effectiveness research. AB - BACKGROUND: Centralized and federated models for sharing data in research networks currently exist. To build multivariate data analysis for centralized networks, transfer of patient-level data to a central computation resource is necessary. The authors implemented distributed multivariate models for federated networks in which patient-level data is kept at each site and data exchange policies are managed in a study-centric manner. OBJECTIVE: The objective was to implement infrastructure that supports the functionality of some existing research networks (e.g., cohort discovery, workflow management, and estimation of multivariate analytic models on centralized data) while adding additional important new features, such as algorithms for distributed iterative multivariate models, a graphical interface for multivariate model specification, synchronous and asynchronous response to network queries, investigator-initiated studies, and study-based control of staff, protocols, and data sharing policies. MATERIALS AND METHODS: Based on the requirements gathered from statisticians, administrators, and investigators from multiple institutions, the authors developed infrastructure and tools to support multisite comparative effectiveness studies using web services for multivariate statistical estimation in the SCANNER federated network. RESULTS: The authors implemented massively parallel (map reduce) computation methods and a new policy management system to enable each study initiated by network participants to define the ways in which data may be processed, managed, queried, and shared. The authors illustrated the use of these systems among institutions with highly different policies and operating under different state laws. DISCUSSION AND CONCLUSION: Federated research networks need not limit distributed query functionality to count queries, cohort discovery, or independently estimated analytic models. Multivariate analyses can be efficiently and securely conducted without patient-level data transport, allowing institutions with strict local data storage requirements to participate in sophisticated analyses based on federated research networks. PMID- 26142425 TI - Biodiesel from waste cooking oil in Mexico City. AB - The aim of this article is to evaluate the potential use of biodiesel produced from waste cooking oil in Mexico City. The study is divided in two main areas: the analysis of a waste cooking oil collection pilot project conducted in food markets of a Mexico City region; and the exhaust emissions performance of biodiesel blends measured in buses of the Mexico City public bus transportation network (RTP). Results from the waste cooking oil collection pilot project show that oil quantities disposed depend upon the type of food served and the operational practices in a cuisine establishment. Food markets' waste cooking oil disposal rate from fresh oil is around 10%, but with a very high standard deviation. Emission tests were conducted using the Ride-Along-Vehicle-Emissions Measuring System in two different types of buses while travelling a regular route. Results shows that the use of biodiesel blends reduces emissions only for buses that have exhaust gas recirculation systems, as analysed by repeated measure analysis of variance. The potential use in Mexico City of waste cooking oil for biodiesel is estimated to cover 2175 buses using a B10 blend. PMID- 26142426 TI - Techno-economic analysis of CHP system supplied by waste forest biomass. AB - Poland, as for Europe, is a country with an average forest cover of approximately 30%. In these forests, more than 37M m3 of wood, mostly coniferous (over 80%), is harvested per year. In 2012, 4.2M m3 of sawn timber was produced (sawn timber without factory lumber). At the same time, in Poland there are over 8000 sawmills, whereas only about 700 of them saw over 90% of the harvested timber. So much fragmentation is a major cause of low sawmills innovation, particularly of those small ones. However, in recent years, a trend of development in this sector is noticeable, and it is through rationalisation of material and energy economy. One of the methods to increase the technical and economic effectiveness of enterprises involved in woodworking is to build in the combined heat and power system (CHP) plant with the ORC system into the existing infrastructure, which will be matched to the needs of the company. This article presents an analysis of the profitability of the investment based on the example of a medium-sized company sawing approximately 50,000 m3 of timber per year, and the economic analysis was performed for prices and costs valid in Poland. The analysis made for the 1650 kW(el) organic Rankine cycle (ORC) system, has resulted in a profitability index PI = 1.3, on the assumptions that the ORC system operates for 6000 h y(-1), will be purchased at the price of 4500 ? kW(el)(-1) and at the price of electricity sales of 130 ? MWh(-1). PMID- 26142427 TI - Altitudinal distribution patterns of AM fungal assemblages in a Tibetan alpine grassland. AB - A better understanding of biogeography of Glomeromycota is essential for the conservation of arbuscular mycorrhizal (AM) fungal species and the ecosystem services that they provide worldwide. We examined the spatial dynamics of AM fungi along two slopes (4149 m a.s.l. to the summit at 5033 m a.s.l.) of Mount Mila on the Tibetan Plateau. Our hypothesis was that AM fungal communities at higher elevation would show distinct assemblages with lower diversity in conditions of increasing environmental harshness. A total of 52 operational taxonomic units (OTUs) spanning all four orders were detected and some OTUs were habitat specific. Nearly 30% of the OTUs were new phylotypes, including two family-like clades. Distinct communities of AM fungi were found at the higher elevation, demonstrating potential niche differentiation along the elevation gradient. Elevation patterns of taxon richness/diversity differed between the two transects, decreasing with increasing elevation on the eastern slope and being unimodal (or lacking a pattern) on the western slope. Taken together, our findings provide evidence of a significant spatial structure of AM fungi across the elevation gradient, with the distribution patterns of these fungi regulated simultaneously by the plant communities, soil properties and climatic conditions in this plateau montane ecosystem. PMID- 26142428 TI - In situ identification and quantification of starch-hydrolyzing bacteria attached to barley and corn grain in the rumen of cows fed barley-based diets. AB - Cereal grains rich in starch are widely used to meet the energy demands of high producing beef and dairy cattle. Bacteria are important players in starch digestion in the rumen, and thus play an important role in the hydrolysis and fermentation of cereal grains. However, our understanding of the composition of the rumen starch-hydrolyzing bacteria (SHB) is limited. In this study, BODIPY FL DQ starch staining combined with fluorescence in situ hybridization (FISH) and quantitative FISH were applied to label, identify and quantify SHB possessing active cell-surface-associated (CSA) alpha-amylase activity in the rumen of heifers fed barley-based diets. When individual cells of SHB with active CSA alpha-amylase activity were enumerated, they constituted 19-23% of the total bacterial cells attached to particles of four different cultivars of barley grain and corn. Quantitative FISH revealed that up to 70-80% of these SHB were members of Ruminococcaceae in the phylum Firmicutes but were not Streptococcus bovis, Ruminobacter amylophilus, Succinomonas amylolytica, Bifidobacterium spp. or Butyrivibrio fibrisolvens, all of whose amylolytic activities have been demonstrated previously in vitro. The proportion of barley grain in the diet had a large impact on the percentage abundance of total SHB and Ruminococcaceae SHB in these animals. PMID- 26142429 TI - Simultaneous determination of telmisartan and amlodipine in dog plasma by LC-MS MS. AB - A simple, rapid and sensitive method was established for the simultaneous determination of telmisartan and amlodipine in dog plasma by a HPLC-MS-MS analysis. The plasma sample preparation was a simple deproteinization by the addition of three volumes of methanol/acetonitrile mixture followed by centrifugation. The analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column with a mobile phase of acetonitrile : water (45 : 55, v/v) at a flow rate of 0.2 mL/min with an operating temperature of 25 degrees C. Detection was carried out by electrospray ionization in positive-ion multiple reaction monitoring mode. The calibration plots in dog plasma were linear over the ranges of 0.5-2,000 ng/mL for telmisartan and 0.5-500 ng/mL for amlodipine. The lower limit of quantification was 0.5 ng/mL for two analytes. The intra- and interday precisions (RSD%) were within 9.0%. The average recoveries of analytes were >85.0%. The method was successfully applied to the pharmacokinetic study of the two compounds after oral administration of telmisartan-amlodipine combination preparation to dogs. PMID- 26142431 TI - Designing and implementing maturity models in hospitals: An experience report from 5 years of research. AB - In recent years, a wide range of generic and domain-specific maturity models have been developed in order to improve organizational design and learning of healthcare organizations. While many of these studies describe methods on how to measure dedicated aspects of a healthcare organization's "maturity," little evidence exists on how to effectively implement and deploy them into practice. This article therefore delineates the encountered challenges during the design and implementation of three maturity models for distinct improvement areas in hospitals. On the one hand, this study's findings may serve as basis for refining existing maturity model design approaches. On the other hand, it may facilitate further research in domain-specific organizational design with maturity models. PMID- 26142430 TI - Transcriptome Differences between Alternative Sex Determining Genotypes in the House Fly, Musca domestica. AB - Sex determination evolves rapidly, often because of turnover of the genes at the top of the pathway. The house fly, Musca domestica, has a multifactorial sex determination system, allowing us to identify the selective forces responsible for the evolutionary turnover of sex determination in action. There is a male determining factor, M, on the Y chromosome (Y(M)), which is probably the ancestral state. An M factor on the third chromosome (III(M)) has reached high frequencies in multiple populations across the world, but the evolutionary forces responsible for the invasion of III(M) are not resolved. To test whether the III(M) chromosome invaded because of sex-specific selection pressures, we used mRNA sequencing to determine whether isogenic males that differ only in the presence of the Y(M) or III(M) chromosome have different gene expression profiles. We find that more genes are differentially expressed between Y(M) and III(M) males in testis than head, and that genes with male-biased expression are most likely to be differentially expressed between Y(M) and III(M) males. We additionally find that III(M) males have a "masculinized" gene expression profile, suggesting that the III(M) chromosome has accumulated an excess of male beneficial alleles because of its male-limited transmission. These results are consistent with the hypothesis that sex-specific selection acts on alleles linked to the male-determining locus driving evolutionary turnover in the sex determination pathway. PMID- 26142432 TI - Feasibility of utilizing a commercial eye tracker to assess electronic health record use during patient simulation. AB - Numerous reports describe unintended consequences of electronic health record implementation. Having previously described physicians' failures to recognize patient safety issues within our electronic health record simulation environment, we now report on our use of eye and screen-tracking technology to understand factors associated with poor error recognition during an intensive care unit based electronic health record simulation. We linked performance on the simulation to standard eye and screen-tracking readouts including number of fixations, saccades, mouse clicks and screens visited. In addition, we developed an overall Composite Eye Tracking score which measured when, where and how often each safety item was viewed. For 39 participants, the Composite Eye Tracking score correlated with performance on the simulation (p = 0.004). Overall, the improved performance was associated with a pattern of rapid scanning of data manifested by increased number of screens visited (p = 0.001), mouse clicks (p = 0.03) and saccades (p = 0.004). Eye tracking can be successfully integrated into electronic health record-based simulation and provides a surrogate measure of cognitive decision making and electronic health record usability. PMID- 26142433 TI - Antigenic Maps of Influenza A(H3N2) Produced With Human Antisera Obtained After Primary Infection. AB - BACKGROUND: Antigenic characterization of influenza viruses is typically based on hemagglutination inhibition (HI) assay data for viral isolates tested against strain-specific postinfection ferret antisera. Here, similar virus characterizations were performed using serological data from humans with primary influenza A(H3N2) infection. METHODS: We screened sera collected between 1995 and 2011 from children between 9 and 24 months of age for influenza virus antibodies, performed HI tests for the positive sera against 23 influenza viruses isolated between 1989 and 2011, and measured HI titers of antisera against influenza A(H3N2) from 24 ferrets against the same panel of viruses. RESULTS: Of the 17 positive human sera, 6 had a high response, showing HI patterns that would be expected from primary infection antisera, while 11 sera had lower, more dispersed patterns of reactivity that are not easily explained. The antigenic map based on the high-response human HI data was similar to the map created using ferret data. CONCLUSIONS: Although the overall structure of the ferret and human antigenic maps is similar, local differences in virus positions indicate that the human and ferret immune system might see antigenic properties of viruses differently. Further studies are needed to establish the degree of similarity between serological patterns in ferret and human data. PMID- 26142434 TI - Cytomegalovirus- and Epstein-Barr Virus-Induced T-Cell Expansions in Young Children Do Not Impair Naive T-cell Populations or Vaccination Responses: The Generation R Study. AB - BACKGROUND: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) induce effector memory T-cell expansions, which are variable and potentially depend on the age at primary exposure and coinfections. We evaluated the T-cell compartment and herpesvirus infections in 6-year-old children. METHODS: T-cell subsets and immunoglobulin G seropositivity for CMV, EBV, herpes-simplex virus 1, and varicella-zoster virus were studied in 1079 6-year-old children. A random subgroup of 225 children was evaluated for CMV and EBV seropositivity before 2 years of age and for vaccination responses against measles and tetanus. RESULTS: CMV and EBV infections were associated with significant expansions of CD27(-) and CD27(+) effector memory T cells, respectively. These expansions were enhanced in CMV-EBV-coinfected children and were independent of varicella-zoster virus or herpes-simplex virus 1 coinfection. Naive and central memory T-cell numbers were not affected, nor were anti-tetanus and anti-measles immunoglobulin G levels. Children infected before 2 years of age showed smaller effector memory T-cell expansions than those infected between 2 and 6 years of age. CONCLUSIONS: CMV- and EBV-related T-cell expansions do not impair naive T-cell numbers or maintenance of protective responses against nonrelated pathogens. Duration of infection was not directly related to larger expansions of effector memory T cells in children, suggesting that other mechanisms affect these expansions at later age. PMID- 26142435 TI - Dynamics of the Human Infectious Reservoir for Malaria Determined by Mosquito Feeding Assays and Ultrasensitive Malaria Diagnosis in Burkina Faso. AB - BACKGROUND: Plasmodium falciparum gametocytes are essential for malaria transmission. Malaria control measures that aim at reducing transmission require an accurate characterization of the human infectious reservoir. METHODS: We longitudinally determined human infectiousness to mosquitoes and P. falciparum carriage by an ultrasensitive RNA-based diagnostics in 130 randomly selected inhabitants of an endemic area. RESULTS: At least 1 mosquito was infected by 32.6% (100 of 307) of the blood samples; in total, 7.6% of mosquitoes (916 of 12 079) were infected. The proportion of infectious individuals and infected mosquitoes were negatively associated with age and positively with asexual parasites (P < .001). Human infectiousness was higher at the start of the wet season and subsequently declined at the peak of the wet season (adjusted odds ratio, 0.52; P = .06) and in the dry season (0.23; P < .001). Overall, microscopy negative individuals were responsible for 28.7% of infectious individuals (25 of 87) and 17.0% of mosquito infections (145 of 855). CONCLUSIONS: Our study reveals that the infectious reservoir peaks at the start of the wet season, with prominent roles for infections in children and submicroscopic infections. These findings have important consequences for strategies and the timing of interventions, which need to include submicroscopic infections and be implemented in the dry season. PMID- 26142436 TI - Human Papillomavirus Vaccination of Boys and Extended Catch-up Vaccination: Effects on the Resilience of Programs. AB - BACKGROUND: Decreasing human papillomavirus (HPV) vaccine prices makes scaling up of vaccination programs attractive for countries that initially targeted 1 or a few birth cohorts of girls and/or achieved low coverage. This article aims to compare the impact of alternative HPV vaccination strategies, using data from Sweden, a high-income country that has experienced vaccine price changes. METHODS: Using an HPV transmission model, we compared the existing vaccination program to alternatives, accounting for a 1-time catch-up vaccination of 22-26 year-old women, with or without routine vaccination of school-age boys, and for a 1-time catch-up vaccination of males aged 13-26 years. We also assessed the resilience of vaccination alternatives to coverage reduction. RESULTS: On the basis of an HPV16/18 prevalence of 12% before the HPV vaccine era, extended catch up vaccination for females and males yielded relative reductions in the HPV prevalence of 49.4% and 55.6%, respectively, during the first 10 years after the start of each vaccination strategy, whereas the existing program yielded a relative reduction of 38.6% during the same period. The increased prevalence reduction due to catch-up vaccination continued for about 30 years. As compared to female-only routine and extended catch-up vaccination, routine vaccination of males with or without catch-up was, respectively, 12.6-fold and 7.2-fold more resilient to coverage reduction. CONCLUSIONS: Vaccination strategies based on catch-up vaccination of females and males are effective for accelerating HPV prevalence reduction. Inclusion of routine male vaccination improves the resilience of vaccination programs. PMID- 26142437 TI - Cancer incidence and incidence rates in Japan in 2009: a study of 32 population based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. AB - The Japan Cancer Surveillance Research Group aimed to estimate the cancer incidence in Japan in 2009 based on data collected from 32 of 37 population-based cancer registries, as part of the Monitoring of Cancer Incidence in Japan (MCIJ) project. The incidence of only primary invasive cancer in Japan for 2009 was estimated to be 775 601. Stomach cancer and breast cancer were the leading types of cancer in males and females, respectively. PMID- 26142438 TI - Whole exome sequencing identifies LRP1 as a pathogenic gene in autosomal recessive keratosis pilaris atrophicans. AB - BACKGROUND: Keratosis pilaris atrophicans (KPA) is a group of rare genodermatoses characterised by perifollicular keratosis and inflammation that progresses to atrophy and scars of the facial skin. Keratosis pilaris of extensor areas of limbs is a common associated finding. Most cases with KPA are sporadic and no consistent inheritance pattern has been documented. METHODS: A large consanguineous Pakistani pedigree segregating autosomal recessive KPA of a mixed type was subject to autozygosity mapping and whole exome sequencing. Quantification of mRNA and protein levels was performed on fibroblasts from affected individuals. Cellular uptake of the low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) ligand alpha2-macroglobulin (alpha(2)M) was quantified using fluorescence confocal microscopy. RESULTS: Genetic analyses identified a unique homozygous missense variant (K1245R) in the LRP1 in all affected family members. LRP1 encodes the LRP1, a multifunctional cell surface receptor with endocytic functions that belongs to the LDL receptor family. The LRP1 mRNA and LRP1 protein levels in fibroblasts of affected individuals were markedly reduced when compared with controls. Similarly, the LRP1-mediated cellular uptake of alpha(2)M was reduced in patient fibroblasts. CONCLUSIONS: This is the first report on LRP1 as a pathogenic gene for autosomal recessive KPA and keratosis pilaris. The inflammatory characteristics of the KPA entity in our family suggest a link to the immune-regulatory functions of LRP1. PMID- 26142439 TI - A Family-Oriented Decision-Making Model for Human Research in Mainland China. AB - This essay argues that individual-oriented informed consent is inadequate to protect human research subjects in mainland China. The practice of family oriented decision-making is better suited to guide moral research conduct. The family's role in medical decision-making originates from the mutual benevolence that exists among family members, and is in accordance with family harmony, which is the aim of Confucian society. I argue that the practice of informed consent for medical research on human subjects ought to remain family-oriented in mainland China. This essay explores the main features of this model of informed consent and demonstrates the proper authority of the family. The family's participation in decision-making as a whole does not negate or deny the importance of the individual who is the subject of the choice, but rather acts more fully to protect research subjects. PMID- 26142440 TI - Intimacy and Family Consent: A Confucian Ideal. AB - In the West, mainstream bioethicists tend to appreciate intimate relationships as a hindrance to individual autonomy. Scholars have even argued against approaching a mother to donate a kidney to save the life of her child; the request, they claim, is too manipulative and, thereby, violates her autonomy. For Chinese bioethicists, such a moral analysis is absurd. The intimate relationship between mother and child establishes strong mutual obligations. It creates mutual moral responsibilities that often require sacrifices for each other. This paper argues that while aiding others is a moral duty, helping one's family is a much stronger duty and poses no threat to one's autonomy. For Confucianism, empathetic intimate feelings, the heart and mind of ren, rest at the root of morality. It requires that we, as moral beings, assume duties to relieve the suffering of others. The more intimate the relationship the stronger the obligation to assist. The family is a closely knitted moral community. Family members often share living resources, mutual experiences, and a sense of identity. Family members act as a social unit, and, ordinarily, mutual obligations among members have priority over duties to those outside of the family. For Confucian bioethics, family-based consent to medical treatment is regarded as natural and reasonable. Family-based decision making is a taken-for-granted norm of social life. While close family members have priority, Confucianism extends such obligations outward toward members of the extended family and the society at large. There is a general principle of gradation of love, which reflects different degrees of personal intimacy and, therefore, of moral obligation. In this fashion, Confucianism seeks to treat the whole of society as one extended family. Hence, in bioethics, mutual responsibility and family-based consent are regarded as basic principles. Through a series of case discussions, this paper illustrates that atomistic individual based autonomy offers but a poor response to bioethical issues. PMID- 26142442 TI - MMP2 and MMP9 as candidate biomarkers to monitor bevacizumab therapy in high grade glioma. PMID- 26142444 TI - First biosimilar drug approved for sale in the United States. PMID- 26142445 TI - Policymakers work to develop e-cigarette guidelines and restrictions. PMID- 26142446 TI - NCI-MATCH launch highlights new trial design in precision-medicine era. PMID- 26142448 TI - Genomic research advances pancreatic cancer's early detection and treatment. PMID- 26142450 TI - Functional adjustments of xylem anatomy to climatic variability: insights from long-term Ilex aquifolium tree-ring series. AB - The present study assessed the effects of climatic conditions on radial growth and functional anatomical traits, including ring width, vessel size, vessel frequency and derived variables, i.e., potential hydraulic conductivity and xylem vulnerability to cavitation in Ilex aquifolium L. trees using long-term tree-ring time series obtained at two climatically contrasting sites, one mesic site in Switzerland (CH) and one drought-prone site in Italy (ITA). Relationships were explored by examining different xylem traits, and point pattern analysis was applied to investigate vessel clustering. We also used generalized additive models and bootstrap correlation functions to describe temperature and precipitation effects. Results indicated modified radial growth and xylem anatomy in trees over the last century; in particular, vessel frequency increased markedly at both sites in recent years, and all xylem traits examined, with the exception of xylem cavitation vulnerability, were higher at the CH mesic compared with the ITA drought site. A significant vessel clustering was observed at the ITA site, which could contribute to an enhanced tolerance to drought-induced embolism. Flat and negative relationships between vessel size and ring width were observed, suggesting carbon was not allocated to radial growth under conditions which favored stem water conduction. Finally, in most cases results indicated that climatic conditions influenced functional anatomical traits more substantially than tree radial growth, suggesting a crucial role of functional xylem anatomy in plant acclimation to future climatic conditions. PMID- 26142453 TI - One Chance to Get it Right: understanding the new guidance for care of the dying person. AB - BACKGROUND: Following criticism of the Liverpool Care of the Dying Pathway (LCP), widely used to guide care of dying people in British health-care settings, the UK Government set up an independent review which in 2013 recommended that use of the LCP be discontinued. In response, the Leadership Alliance for the Care of Dying People, a coalition of a wide range of stakeholders, recently published guidance entitled One Chance to Get it Right. This guidance contains five Priorities of Care for the dying person that are intended to guide clinical staff and will inform Care Quality Commission inspections of health-care providers. This article summarizes the background to One Chance to Get it Right and the guidance it contains. SOURCES OF DATA: One Chance to Get it Right, More Care, Less Pathway and related guidance documents. AREAS OF AGREEMENT: The need to improve the standard of end-of-life care in every clinical setting. AREAS OF CONTROVERSY: The value of a pathway-based approach to end-of-life care in a context where well implemented programmes of staff education in the subject are lacking. GROWING POINTS: Public concern with, and scrutiny of, the quality of dying in the UK health-care system, particularly in hospitals but also the ability of patients to die well at home where that is their place of choice. AREAS TIMELY FOR DEVELOPING RESEARCH: Effective methods of teaching end of life care to all clinical staff; the effect upon families of caring for a dying relative at home; the optimum type, quantity and source of external support to informal carers that is perceived by them as adequate and enables the ill person to die well in in their own home; fuller understanding of the physiology of dying. PMID- 26142452 TI - Acyclovir Prophylaxis Reduces the Incidence of Herpes Zoster Among HIV-Infected Individuals: Results of a Randomized Clinical Trial. AB - Human immunodeficiency virus (HIV)-infected persons have higher rates of herpes zoster than HIV-uninfected individuals. We assessed whether twice daily treatment with 400 mg of oral acyclovir reduces the incidence of herpes zoster in a randomized, double-blind, placebo-controlled trial among 3408 persons coinfected with HIV and herpes simplex virus type 2. During 5175 person-years of follow-up, 26 cases of herpes zoster occurred among those assigned acyclovir, compared with 69 cases among those assigned placebo (rates, 1.00 and 2.68/100 person-years, respectively), a relative decrease of 62% (hazard ratio, 0.38; 95% confidence interval, .24-.67; P < .001). Daily acyclovir prophylaxis significantly reduced herpes zoster incidence among HIV-infected persons. PMID- 26142451 TI - The global distribution of Crimean-Congo hemorrhagic fever. AB - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection caused by a virus (CCHFV) from the Bunyaviridae family. Domestic and wild vertebrates are asymptomatic reservoirs for the virus, putting animal handlers, slaughter-house workers and agricultural labourers at highest risk in endemic areas, with secondary transmission possible through contact with infected blood and other bodily fluids. Human infection is characterized by severe symptoms that often result in death. While it is known that CCHFV transmission is limited to Africa, Asia and Europe, definitive global extents and risk patterns within these limits have not been well described. METHODS: We used an exhaustive database of human CCHF occurrence records and a niche modeling framework to map the global distribution of risk for human CCHF occurrence. RESULTS: A greater proportion of shrub or grass land cover was the most important contributor to our model, which predicts highest levels of risk around the Black Sea, Turkey, and some parts of central Asia. Sub-Saharan Africa shows more focalized areas of risk throughout the Sahel and the Cape region. CONCLUSIONS: These new risk maps provide a valuable starting point for understanding the zoonotic niche of CCHF, its extent and the risk it poses to humans. PMID- 26142454 TI - Coronary vein pacing with standard active fixation leads for cardiac resynchronization. PMID- 26142455 TI - Activation of Protein Kinases and Phosphatases Coupled to Glutamate Receptors Regulates the Phosphorylation State of DARPP32 at Threonine 75 After Repeated Exposure to Cocaine in the Rat Dorsal Striatum in a Ca2+-Dependent Manner. AB - BACKGROUND: Phosphorylation state of dopamine- and cAMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP32) is crucial to understand drug-mediated synaptic plasticity. In this study, mechanisms underlying repeated cocaine-stimulated phosphorylation of DARPP32 at threonine 75 (pDARPP32-Thr75) were determined by investigating the hypothesis that activation of protein kinases and phosphatases coupled to glutamate signaling is necessary for the regulation of pDARPP32-Thr75 after repeated cocaine administration. METHODS: Intracaudate drug infusions into the rat dorsal striatum followed by Western immunoblot analysis were mainly performed to test this hypothesis. RESULTS: The results demonstrated that 7 repeated daily intraperitoneal injections of cocaine (20mg/kg) upregulated the expression of pDARPP32-Thr75. Increases in the cytosolic Ca(2+) concentrations followed by Ca(2+)-dependent protein kinase activation through stimulation of Ca(2+) channels in striatal neurons were necessary for the phosphorylation. Activation of protein phosphatases further regulated the phosphorylation state by deactivating pDARPP32-Thr75 and upstream protein kinases. CONCLUSION: These findings suggest that activation of protein kinases and phosphatases coupled to glutamate receptors controls the phosphorylation state of DARPP32-Thr75 after repeated exposure to cocaine in the dorsal striatum in a Ca(2+)-dependent manner. PMID- 26142456 TI - Effects of hypobaric hypoxia exposure at high altitude on left ventricular twist in healthy subjects: data from HIGHCARE study on Mount Everest. AB - AIMS: Previous studies investigating the effect of hypoxia on left ventricle focused on its global function, an approach that may not detect a selective dysfunction of subendocardial layers that are most sensitive to an inadequate oxygen supply. In the HIGHCARE study, aimed at exploring the effects of high altitude hypoxia on multiple biological variables and their modulation by an angiotensin receptor blocker, we addressed the effects of hypobaric hypoxia on both systolic and diastolic left ventricular geometry and function, focusing on echocardiographic assessment of left ventricle twist to indirectly examine subendocardial left ventricular systolic function. METHODS AND RESULTS: In 39 healthy subjects, physiological and echocardiographic variables, including left ventricular twist and a simplified torsion-to-shortening ratio (sTSR), were recorded at sea level, at 3400 m, and at 5400 m altitude (Mount Everest base camp). Both left ventricular twist and sTSR were greater at 5400 m than at sea level (12.6 degrees vs. 9.6 degrees and 0.285 vs. 0.202, P < 0.05 for both), were linearly related to the reduction in arterial oxygen partial pressure (P < 0.01 for both), and were associated with significant changes in LV dimensions and contractility. No effects of angiotensin receptor blockade were observed on these variables throughout the study. CONCLUSION: Our study, for the first time, demonstrates an increase in left ventricular twist at high altitude in healthy subjects exposed to high altitude hypoxia, suggesting the occurrence of subendocardial systolic dysfunction in such condition. PMID- 26142458 TI - Black necrotic oesophagus following the use of biodegradable stent for benign oesophageal stricture. AB - Biodegradable stents are increasingly being used for benign oesophageal conditions that include refractory strictures and perforations. Acute oesophageal necrosis has been reported with various other conditions but none due to the insertion of biodegradable stents. A 58-year-old male presented as an acute emergency in severe haemodynamic shock. Investigations confirmed an oesophageal perforation. He underwent an emergency surgical intervention that identified extensive necrosis of the oesophagus requiring thoracic oesophagectomy, cervical oesophagostomy and a feeding jejunostomy as a damage control procedure. This was followed a month later, by successful reconstruction using a gastric conduit. This is the first reported case of a necrosis of the oesophagus following insertion of two biodegradable stents for a benign oesophageal stricture and highlights this rare but very serious life-threatening complication. PMID- 26142457 TI - Functional effects of distinct innervation styles of pyramidal cells by fast spiking cortical interneurons. AB - Inhibitory interneurons target precise membrane regions on pyramidal cells, but differences in their functional effects on somata, dendrites and spines remain unclear. We analyzed inhibitory synaptic events induced by cortical, fast-spiking (FS) basket cells which innervate dendritic shafts and spines as well as pyramidal cell somata. Serial electron micrograph (EMg) reconstructions showed that somatic synapses were larger than dendritic contacts. Simulations with precise anatomical and physiological data reveal functional differences between different innervation styles. FS cell soma-targeting synapses initiate a strong, global inhibition, those on shafts inhibit more restricted dendritic zones, while synapses on spines may mediate a strictly local veto. Thus, FS cell synapses of different sizes and sites provide functionally diverse forms of pyramidal cell inhibition. PMID- 26142459 TI - Thermoluminescence characteristics of Zn(BO2)2:Ce3+ under beta irradiation. AB - In this study, the thermoluminescence (TL) characteristics of undoped and various Ce(3) (+)-doped Zn(BO2)2 powder samples excited by beta irradiation are reported for the first time. Zn(BO2)2:Ce(3+) powder samples were prepared by the nitric acid method (NAM) using the starting oxides [zinc oxide (ZnO), boric acid (H3BO3) and doped element oxide (CeO2)]. The formations of the obtained samples were confirmed by an X-ray diffraction study. Dose responses of Ce(3) (+)-doped Zn(BO2)2 samples were investigated after the beta irradiation in the dose range from 143 mGy to 60 Gy. All TL measurements were made on using an automated Riso TL/OSL DA-20 reader. TL emission was detected through a filter pack (Schott BG-39 and Corning 7-59) transmitting between 330 and 480 nm. TL glow curves were obtained using a constant heating rate of 5 degrees C s(-1) from room temperature (RT) to 450 degrees C in an N2 atmosphere. The dose response and minimum detectable dose (MDD) values of the samples were determined. The dose responses of all the samples tested exhibited a superlinear behaviour. MDD value of 4 % Ce(3) (+)-doped Zn(BO2)2 sample, which shows a high temperature peak at about 230 degrees C, was determined as 96 mGy. MDD values for 1, 2, 3, 5 and 10 % Ce(3) (+) doped Zn(BO2)2 samples were also determined as 682, 501, 635, 320 and 824 mGy, respectively. The trap parameters of undoped and 4 % Ce(3) (+)-doped Zn(BO2)2 samples were estimated by the computerised glow curve deconvolution method. PMID- 26142460 TI - The impact of virulence factors of Porphyromonas gingivalis on wound healing in vitro. AB - BACKGROUND: Porphyromonas gingivalis inhibits oral epithelial wound healing in vitro more strongly than other oral bacteria, but it is unknown why P. gingivalis is such a potent inhibitor of wound healing. OBJECTIVE: Therefore, the aim of this study was to investigate the influence of major virulence factors of P. gingivalis on wound healing in an in vitro wound-healing model. The influence of the capsular polysaccharide, the Arg- and Lys- gingipains, the major fimbriae and lipopolysaccharide (LPS) was investigated. DESIGN: A standardized scratch was made in a confluent layer of human oral epithelial cells HO-1-N-1. The epithelial cells were then challenged with different concentrations of several P. gingivalis wild-type strains and knockout mutants. Closure of the scratch was determined after 17 h and compared to control conditions without bacteria. RESULTS: The P. gingivalis strains ATCC 33277, W83, and W50 significantly inhibited wound healing. The presence of a capsular polysaccharide lowered significantly the inhibition of epithelial cell migration, while gingipain activity significantly increased the inhibition of cell migration. LPS and the major fimbriae did not influence epithelial cell migration. None of the tested P. gingivalis strains completely prevented the inhibition of cell migration, suggesting that other characteristics of P. gingivalis also play a role in the inhibition of wound healing, and that further research is needed. CONCLUSIONS: The capsular polysaccharide and the Arg- and Lys- gingipains of P. gingivalis influenced the capacity of P. gingivalis to hinder wound healing, while LPS and the major fimbriae had no effect. PMID- 26142461 TI - Physical exercise induces rapid release of small extracellular vesicles into the circulation. AB - Cells secrete extracellular vesicles (EVs) by default and in response to diverse stimuli for the purpose of cell communication and tissue homeostasis. EVs are present in all body fluids including peripheral blood, and their appearance correlates with specific physiological and pathological conditions. Here, we show that physical activity is associated with the release of nano-sized EVs into the circulation. Healthy individuals were subjected to an incremental exercise protocol of cycling or running until exhaustion, and EVs were isolated from blood plasma samples taken before, immediately after and 90 min after exercise. Small EVs with the size of 100-130 nm, that carried proteins characteristic of exosomes, were significantly increased immediately after cycling exercise and declined again within 90 min at rest. In response to treadmill running, elevation of small EVs was moderate but appeared more sustained. To delineate EV release kinetics, plasma samples were additionally taken at the end of each increment of the cycling exercise protocol. Release of small EVs into the circulation was initiated in an early phase of exercise, before the individual anaerobic threshold, which is marked by the rise of lactate. Taken together, our study revealed that exercise triggers a rapid release of EVs with the characteristic size of exosomes into the circulation, initiated in the aerobic phase of exercise. We hypothesize that EVs released during physical activity may participate in cell communication during exercise-mediated adaptation processes that involve signalling across tissues and organs. PMID- 26142463 TI - Expecting to See a Letter: Alpha Oscillations as Carriers of Top-Down Sensory Predictions. AB - Predictions strongly influence perception. However, the neurophysiological processes that implement predictions remain underexplored. It has been proposed that high- and low-frequency neuronal oscillations act as carriers of sensory evidence and top-down predictions, respectively (von Stein and Sarnthein 2000; Bastos et al. 2012). However, evidence for the latter hypothesis remains scarce. In particular, it remains to be shown whether slow prestimulus alpha oscillations in task-relevant brain regions are stronger in the presence of predictions, whether they influence early categorization processes, and whether this interplay indeed boosts perception. Here, we directly address these questions by manipulating subjects' prior expectations about the identity of visually presented letters while collecting magnetoencephalographic recordings. We find that predictions lead to increased prestimulus alpha oscillations in a multisensory network representing grapheme/phoneme associations. Furthermore, alpha power interacts with stimulus degradation and top-down expectations to predict visibility ratings, and correlates with the amplitude of early sensory components (P1/N1m complex), suggesting a role in the selective amplification of predicted information. Our results thus indicate that low-frequency alpha oscillations can serve as a mechanism to carry and test sensory predictions about letters. PMID- 26142462 TI - Remapping, Spatial Stability, and Temporal Continuity: From the Pre-Saccadic to Postsaccadic Representation of Visual Space in LIP. AB - As our eyes move, we have a strong percept that the world is stable in space and time; however, the signals in cortex coming from the retina change with each eye movement. It is not known how this changing input produces the visual percept we experience, although the predictive remapping of receptive fields has been described as a likely candidate. To explain how remapping accounts for perceptual stability, we examined responses of neurons in the lateral intraparietal area while animals performed a visual foraging task. When a stimulus was brought into the response field of a neuron that exhibited remapping, the onset of the postsaccadic representation occurred shortly after the saccade ends. Whenever a stimulus was taken out of the response field, the presaccadic representation abruptly ended shortly after the eyes stopped moving. In the 38% (20/52) of neurons that exhibited remapping, there was no more than 30 ms between the end of the presaccadic representation and the start of the postsaccadic representation and, in some neurons, and the population as a whole, it was continuous. We conclude by describing how this seamless shift from a presaccadic to postsaccadic representation could contribute to spatial stability and temporal continuity. PMID- 26142464 TI - Impact of Crohn's Disease on Marital Quality of Life: A Preliminary Cross Sectional Study. AB - BACKGROUND AND AIMS: Quality of marriage exerts a great effect on quality of life [QOL] and health outcomes. Few data are available on the effects of Crohn's disease [CD] on quality of marriage. We aimed to clarify whether and how CD affected the marital relationship. METHODS: Web-based questionnaires were created including an ENRICH marital inventory, a general QOL survey [SF12], a short Inflammatory Bowel Disease Questionnaire [SIBDQ] and a modified Harvey-Bradshaw Index [HBI]. Married patients were enrolled through the outpatient registration system and diverse social media websites. Controls were subsequently enrolled and matched with the ratio of 1:1 through invitation emails and internet advertising. RESULTS: A total of 243 patients completed valid questionnaires and then 243 matched individuals were enrolled. Male patients were more affected, representing a significantly reduced total marital score. CD impaired the dimensions of idealistic distortion and marital satisfaction in both genders. There were correlations between quality of marriage, SF12, SIBDQ and HBI. Mental scale of SF12 correlated best with the marital relationship, indicating more significant involvement of mental adjustment. Multiple linear regression demonstrated that spouse's educational background, duration of marriage from disease onset, enteral nutrition, hospitalisation in past 12 months, and number of previous hospitalisations, independently impacted on quality of marriage. CONCLUSIONS: Certain aspects of the marital relationship were impaired in CD patients, especially in male subjects. In addition to medication, mental interventions should be given attention to improve the marriage of CD patients. Despite some novel findings in this study, this research orientation deserves more attention. PMID- 26142465 TI - Anti-tumour Necrosis Factor Treatment with Adalimumab Induces Changes in the Microbiota of Crohn's Disease. AB - BACKGROUND: The composition of the intestinal microbiota is altered in Crohn's disease [CD] patients. The objective of this study was to evaluate the qualitative and quantitative changes in the microbiota of CD patients in 3 months of treatment with adalimumab [ADA], and determine whether or not these changes are produced towards the recovery of the normal, healthy-like microbiota. METHODS: The microbiota composition, and the Faecalibacterium prausnitzii / Escherichia coli quantitative relationship as dysbiosis indicator, were studied at baseline [T0], one month [T1], and 3 months [T3] after starting treatment using a polymerase chain reaction-denaturing gradient gel electrophoresis [PCR DGGE] of 16S rRNA gene fragments and quantitative PCR, respectively, in rectal mucosal biopsies from 15 CD patients and four healthy subjects. RESULTS: T0 and T3 fingerprints were different in all patients; whereas T1 and T3 presented similar patterns. Recovered phylogroups were Firmicutes [79.1%], Bacteroides [12.5%], and Actinobacteria [6.25%]. The prevalence of E. coli decreased during treatment. Relative E. coli loads in CD samples were significantly reduced at every analysed step [T1 and T3] [p < 0.005] whereas no significant changes were observed in relative F. prausnitzii counts. CONCLUSION: Treatment with ADA induces short-term changes in the microbiota composition which seem to parallel the partial recovery of the gut bacterial ecology, with recovery parameters tending to eubiosis recovery. The quantitative determination of dysbiosis representative bacteria, such as E. coli, may provide a fast and reliable indicator of the healing state of the intestinal mucosa. PMID- 26142466 TI - Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes. AB - AIMS: We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol <=1.8 mmol/L. CONCLUSION: A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required. PMID- 26142467 TI - Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications. AB - Systolic and diastolic myocardial dysfunction has been demonstrated to be associated with an activation of the circulating and local renin-angiotensin aldosterone system (RAAS), and with a subsequent inappropriately increased production of reactive oxygen species (ROS). While, at low concentrations, ROS modulate important physiological functions through changes in cellular signalling and gene expression, overproduction of ROS may adversely alter cardiac mechanics, leading to further worsening of systolic and diastolic function. In addition, vascular endothelial dysfunction due to uncoupling of the nitric oxide synthase, activation of vascular and phagocytic membrane oxidases or mitochondrial oxidative stress may lead to increased vascular stiffness, further compromising cardiac performance in afterload-dependent hearts. In the present review, we address the potential role of ROS in the pathophysiology of myocardial and vascular dysfunction in heart failure (HF) and their therapeutic targeting. We discuss possible mechanisms underlying the failure of antioxidant vitamins in improving patients' prognosis, the impact of angiotensin-converting enzyme inhibitors or AT1 receptor blockers on oxidative stress, and the mechanism of the benefit of combination of hydralazine/isosorbide dinitrate. Further, we provide evidence supporting the existence of differences in the pathophysiology of HF with preserved vs. reduced ejection fraction and whether targeting mitochondrial ROS might be a particularly interesting therapeutic option for patients with preserved ejection fraction. PMID- 26142468 TI - Management of oral and gastrointestinal mucosal injury: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. PMID- 26142469 TI - Outcome after coronary artery bypass grafting and percutaneous coronary intervention in patients with stage 3b-5 chronic kidney disease. AB - OBJECTIVES: Patients with chronic kidney disease (CKD) are generally considered to be at an increased risk for cardiovascular events and cardiac mortality. The prognostic significance of severe renal impairment in patients undergoing coronary revascularization remains mainly unknown because these patients have been excluded from randomized clinical trials. The aim of the present study was to compare the outcome after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with an estimated glomerular filtration rate (eGFR) of <45 ml/min/m(2). METHODS: This retrospective study includes 110 patients who underwent PCI and 148 patients who underwent isolated CABG between 2007 and 2010. All patients had stage 3b-5 CKD (eGFR <45 ml/min/m(2)). RESULTS: The median follow-up time was 25 (interquartile range 30) months. At 30 days and 3 years, postoperative de novo dialysis was required in 3.4 and 16.2% of CABG patients and in 0 and 6.6% (P = 0.10) of PCI patients. PCI was associated with similar mortality at 30 days (PCI 10.0% and CABG 12.2%, P = 0.068). At 3 years, PCI was associated with a significantly higher risk of mortality (50.4 vs 32.9, adjusted analysis: HR 1.77, 95% CI 1.13-2.77), repeat revascularization (20.3 vs 0.8%, too few for adjusted analysis) and major adverse cardiac and cerebrovascular events (57.8 vs 34.3%, HR 2.19, 95% CI 1.41-3.40). These findings were supported by propensity score-matched analysis. CONCLUSION: Patients with moderate to severe CKD have a high rate of mortality and morbidity after either PCI or CABG. The fear of postoperative dialysis rates after CABG appears overemphasized since less than 5% of patients needed dialysis in the early postoperative period. This study provides evidence that this high-risk subset of patients should also be revascularized according to general recommendations. When feasible, CABG could be associated with better survival and freedom from cardiovascular events than PCI. PMID- 26142470 TI - Reply to West. PMID- 26142471 TI - A retrospective review comparing treatment outcomes of adjuvant lung resection for drug-resistant tuberculosis in patients with and without human immunodeficiency virus co-infection. AB - OBJECTIVES: This review was undertaken to compare treatment outcomes in human immunodeficiency virus (HIV) negative versus HIV-positive patients following adjuvant lung resection for drug-resistant tuberculosis (DR-TB) in patients deemed feasible for surgery. Despite appropriate medical therapy, mortality remains extremely high and cure rates poor in patients with DR-TB and HIV co infection. Therefore, adjuvant lung resection may warrant a more prominent role in the treatment of these patients. METHODS: A retrospective review of all case records from 1 January 2012 to 31 March 2013 of all patients admitted to the Department of Cardiothoracic Surgery King Dinuzulu Hospital with DR-TB and treated with adjuvant lung resection was undertaken. Prior to surgery, all patients were treated for at least 3 months with appropriate drug therapy for DR TB. This was continued for the recommended period following lung resection. RESULTS: Fourteen patients with extensively drug-resistant tuberculosis (XDR-TB) were deemed suitable for lung resection. Of these patients, 10 patients were HIV positive and 4 were HIV-negative. In the XDR-TB/HIV-positive group, 7 patients were cured, 2 converted and 2 patients developed a post-pneumonectomy broncho pleural fistula. One patient was lost to follow-up. In the XDR-TB/HIV-negative group, 1 patient was cured, 3 converted and 1 patient developed a post thoracotomy superficial wound infection. There was no in-hospital mortality in both groups. Thirty-six patients with multi-drug-resistant tuberculosis (MDR-TB) were deemed suitable for lung resection. Of these patients, 19 were HIV-positive and 17 HIV-negative. In the MDR-TB/HIV-positive group, 12 patients were cured and 6 converted. One patient developed a post-thoracotomy superficial wound infection and another patient who developed a post-pneumonectomy empyema thoracis was also regarded as a treatment failure. In the MDR-TB/HIV-negative group, 15 patients were cured, 2 converted and 1 patient developed a post-pneumonectomy lower respiratory tract infection which necessitated a short period of mechanical ventilation. There was no in-hospital mortality in both groups. CONCLUSIONS: Lung resection for DR-TB may be safely undertaken in selected patients who are HIV positive with cure rates equivalent to that of HIV-negative patients. More importantly, these patients also have significantly higher cure rates than those patients treated with medical therapy alone. PMID- 26142472 TI - Cardiothoracic surgery remains an attractive career in the United Kingdom. PMID- 26142473 TI - Systolic anterior motion after mitral valve repair: where do we stand in 2015? PMID- 26142475 TI - Time-kill kinetics of slowly growing mycobacteria common in pulmonary disease. AB - OBJECTIVES: This study aimed to provide basic pharmacodynamic information for key antibiotics used to treat Mycobacterium avium and Mycobacterium xenopi pulmonary disease. METHODS: M. avium subspecies hominissuis IWGMT49 and M. xenopi ATCC 19250 type strains were used; the MICs of clarithromycin, amikacin and moxifloxacin were determined by broth microdilution. Time-kill assays were performed, exposing bacteria to 2-fold concentrations from 0.062* to 32* the MIC at 37 degrees C for 240 h for M. avium or 42 days for M. xenopi. The sigmoid maximum effect (Emax) model was fitted to the time-kill curve data. RESULTS: Maximum killing of M. avium by amikacin was obtained between 24 and 120 h (0.0180 h(-1)) and was faster and higher than with clarithromycin (0.0109 h(-1)); however, regrowth and amikacin-resistant mutants were observed. Killing rates for M. xenopi were higher, 0.1533 h(-1) for clarithromycin and 0.1385 h(-1) for moxifloxacin, yet required 42 days. There were no significant differences between the Hill's slopes determined for all of the antibiotics tested against M. avium or M. xenopi (P = 0.9663 and P = 0.0844, respectively). CONCLUSIONS: The killing effect of amikacin and clarithromycin on M. avium subspecies hominissuis was low, although amikacin activity was higher than that of clarithromycin, supporting its role in a combined therapy. Clarithromycin and moxifloxacin may have similar activity within treatment regimens for M. xenopi disease. Future studies of in vitro and in vivo pharmacokinetic/pharmacodynamic interactions are needed to improve the current regimens to treat these two important slowly growing mycobacteria in pulmonary disease. PMID- 26142474 TI - Declining macrolide resistance in Streptococcus pyogenes in Portugal (2007-13) was accompanied by continuous clonal changes. AB - OBJECTIVES: Macrolide resistance among Streptococcus pyogenes [group A streptococci (GAS)] in Portugal decreased between 1999 and 2006 and this decrease was accompanied by alterations in the prevalence of macrolide resistance phenotypes and clonal composition of the population. The aims of this study were to determine the macrolide resistance rate, resistance phenotypes and clones of GAS recovered from pharyngitis in 2007-13 in Portugal. METHODS: Antimicrobial susceptibility was tested by disc diffusion. Macrolide-resistant isolates were characterized by emm typing, T typing, PFGE profiling and MLST, and the presence of macrolide resistance determinants was determined by PCR. RESULTS: We found continuing changes in macrolide resistance phenotypes and a persistent decline in overall erythromycin resistance, from 10% in 2007 to 1% in 2013. During this period there was a marked increase in emm11-ST403 cMLSB isolates, the disappearance of the emm3-ST315 M lineage and changes in the prevalence of previously identified GAS clones. Unexpectedly, the decline in erythromycin resistance and the decreasing prevalence of the MLSB phenotype were accompanied by a high consumption of long-acting and intermediate-acting macrolides, known to select for resistance and particularly for the erm(B) gene. CONCLUSIONS: The continuous decline in macrolide resistance detected since 2000, accompanied by a high clonal instability, emphasizes the importance of considering factors other than antibiotic consumption in explaining the prevalence of macrolide-resistant GAS. PMID- 26142476 TI - Dolutegravir maintains a durable effect against HIV replication in tissue culture even after drug washout. AB - OBJECTIVES: Of the currently approved HIV integrase strand transfer inhibitors (INSTIs), dolutegravir has shown greater efficacy than raltegravir at suppressing HIV-1 replication in treatment-experienced individuals. Biochemical experiments have also shown that dolutegravir has a longer dissociative half-life when bound to HIV integrase than does raltegravir. In order to study the intracellular efficacy of various INSTIs, we asked whether drug removal from INSTI-treated HIV 1-infected cells would result in different times to viral rebound. In addition, we assessed the role of the R263K substitution within the integrase ORF that is associated with low-level resistance to dolutegravir. METHODS: HIV-infected MT-2 cells were treated with dolutegravir, raltegravir or a third experimental INSTI (MK-2048) and the drugs were washed out after varying times. Viral replication was monitored by measuring reverse transcriptase (RT) activity in the culture fluids. RESULTS: We observed a significantly slower increase in RT activity after the removal of dolutegravir compared with raltegravir or MK-2048. The incubation time before the drug was removed also had an impact on the level of RT activity independently of the drug and virus used. The R263K substitution did not significantly impact on levels of RT activity after drug washout, suggesting that dolutegravir remained tightly bound to the integrase enzyme despite the presence of this mutation. CONCLUSIONS: These results suggest that the residency time of INSTIs on integrase is a key factor in the activity of these drugs and that the anti-HIV activity of dolutegravir persists more effectively than that of other INSTIs after drug washout. PMID- 26142477 TI - Auranofin efficacy against MDR Streptococcus pneumoniae and Staphylococcus aureus infections. AB - BACKGROUND: Auranofin is an FDA-approved, gold-containing compound in clinical use for the oral treatment of rheumatoid arthritis and has been recently granted by the regulatory authorities due to its antiprotozoal properties. METHODS: A reprofiling strategy was performed with a Streptococcus pneumoniae phenotypic screen and a proprietary library of compounds, consisting of both FDA-approved and unapproved bioactive compounds. Two different multiresistant S. pneumoniae strains were employed in a sepsis mouse model of infection. In addition, an MRSA strain was tested using both the thigh model and a mesh-associated biofilm infection in mice. RESULTS: The repurposing approach showed the high potency of auranofin against multiresistant clinical isolates of S. pneumoniae and Staphylococcus aureus in vitro and in vivo. Efficacy in the S. pneumoniae sepsis model was obtained using auranofin by the oral route in the dose ranges used for the treatment of rheumatoid arthritis. Thioglucose replacement by alkyl chains showed that this moiety was not essential for the antibacterial activity and led to the discovery of a new gold derivative (MH05) with remarkable activity in vitro and in vivo. CONCLUSIONS: Auranofin and the new gold derivative MH05 showed encouraging in vivo activity against multiresistant clinical isolates of S. pneumoniae and S. aureus. The clinical management of auranofin, alone or in combination with other antibiotics, deserves further exploration before use in patients presenting therapeutic failure caused by infections with multiresistant Gram-positive pathogens. Decades of clinical use mean that this compound is safe to use and may accelerate its evaluation in humans. PMID- 26142478 TI - Pathogens of skin and skin-structure infections in the UK and their susceptibility to antibiotics, including ceftaroline. AB - OBJECTIVES: Bacterial skin and skin-structure infections (SSSIs) are frequent settings for antibiotic use. We surveyed their UK aetiology and pathogen susceptibility, including susceptibility to ceftaroline. METHODS: Consecutive SSSI isolates were collected at 35 UK hospitals, to a maximum of 60/site, together with 15 'supplementary' MRSA/site. Isolates were re-identified and BSAC susceptibility testing was performed, with parallel CLSI agar testing for ceftaroline. RESULTS: Isolates (n = 1908) were collected from 1756 hospitalized patients, predominantly with surgical and traumatic infections, abscesses and infected ulcers and largely from general medicine and general surgery patients. They included 1271 Staphylococcus aureus (201 MRSA), 162 beta-haemolytic streptococci, 269 Enterobacteriaceae, 138 Pseudomonas aeruginosa and 37 enterococci. Most (944/1756) patients had monomicrobial MSSA infections. Rates of resistance to quinolones, gentamicin and cephalosporins were <20% in Enterobacteriaceae and <10% in P. aeruginosa. MRSA rates varied greatly among hospitals and were 2.5-fold higher in general medicine than in general surgery patients. At breakpoint, ceftaroline inhibited: (i) all MSSA and 97.6% of MRSA, with MICs of 2 mg/L for the few resistant MRSA; (ii) all beta-haemolytic streptococci; and (iii) 83% of Enterobacteriaceae. High-level ceftaroline resistance in Enterobacteriaceae involved ESBLs or AmpC enzymes. Ceftaroline MICs by CLSI methodology generally equalled those by BSAC or were 2-fold higher, but this differential was 4-16-fold for P. aeruginosa. CONCLUSIONS: Irrespective of patient group, SSSIs were dominated by S. aureus. Most pathogens were susceptible, but 15.8% of S. aureus were MRSA, with locally higher prevalence. PMID- 26142479 TI - Epidemiology and molecular typing of VRE bloodstream isolates in an Irish tertiary care hospital. AB - OBJECTIVES: Ireland has the highest rate of vancomycin-resistant Enterococcus faecium (VREfm) isolated from blood of nosocomial patients in Europe, which rose from 33% (110/330) in 2007 to 45% (178/392) in 2012. No other European country had a VREfm rate from blood cultures of >25%. Our aim was to elucidate the reasons for this significantly higher rate in Ireland. METHODS: The epidemiology and molecular typing of VRE from bloodstream infections (BSIs) was examined in a tertiary care referral hospital and isolates were compared with those from other tertiary care referral centres in the region. RESULTS: The most common source of VRE BSIs was intra-abdominal sepsis, followed by line-related infection and febrile neutropenia. Most of the isolates were positive for vanA; 52% (43/83) possessed the esp gene and 12% (10/83) possessed the hyl gene. Genotyping by SmaI macrorestriction analysis (PFGE) of isolates revealed clonal relatedness between bloodstream isolates and environmental isolates. VRE BSI isolates from two other tertiary care hospitals in the Dublin region showed relatedness by PFGE analysis. MLST revealed four STs (ST17, ST18, ST78 and ST203), all belonging to the clonal complex of hospital-associated strains. CONCLUSIONS: Irish VRE BSI isolates have virulence factor profiles as previously reported from Europe. Typing analysis shows the spread of individual clones within the hospital and between regional tertiary care hospitals. Apart from transmission of VRE within the hospital and transfer of colonized patients between Irish hospitals, no other explanation for the persistently high VREfm BSI rate in Ireland has been found. PMID- 26142481 TI - Retraction. AB - Histopathological Features of Capillaria hepatica Infection in Laboratory Rabbits. Toxicol Pathol 37, 661-666. (Original DOI: 10.1177/0192623309339501). PMID- 26142482 TI - Development and initial testing of a GDM information website for multi-ethnic women with GDM. AB - BACKGROUND: Gestational diabetes mellitus (GDM) affects approximately 5-15 % of pregnant women in Australia. Highest rates are seen among women who are obese, from specific ethnic backgrounds and low socio-economic circumstance. These features also impact on uptake of self-management recommendations. GDM that is not well managed can give rise to serious pregnancy complications. The aim of this project was to develop and test an intervention to improve knowledge of GDM and GDM self-management principles. METHODS: A web-based intervention, consisting of resources aimed at a low level of literacy, was developed and tested among multi-ethnic women at a metropolitan hospital in Melbourne Australia. A basic one group pre-test/post-test design was used to explore the impact of the intervention on knowledge, in 3 domains: (1) Knowledge of GDM; (2) food values, and;(3) GDM self-management principles. Questionnaire data was analysed using Statistical Package for the Social Sciences (SPSS), version 21.0. Fisher's exact test was used to test for an improvement in each knowledge scale. RESULTS: Twenty one women with GDM, from multi-ethnic backgrounds, participated in the testing of the intervention. Results indicated that the intervention was effective at improving knowledge scores and this effect was greatest in the first domain, knowledge of GDM. Although some improvement of knowledge scores occurred in the other two domains, food values and self-management principles, these improvements were less than expected. This finding may relate to a number of misunderstandings in the interpretation of the web resource and survey questions. These issues will need to be resolved prior to proceeding to a clinical trial. CONCLUSION: Initial results from this study look promising and suggest that with some improvements, the intervention could prove a useful adjunct support for women with GDM from multi-ethnic and low socio-economic backgrounds. Conducting a randomised controlled trial is feasible in the future and will provide a useful means of examining efficacy of the intervention. PMID- 26142483 TI - A brief report on the development of a theoretically-grounded intervention to promote patient autonomy and self-management of physiotherapy patients: face validity and feasibility of implementation. AB - BACKGROUND: Clinical practice guidelines for the treatment of low back pain suggest the inclusion of a biopsychosocial approach in which patient self management is prioritized. While many physiotherapists recognise the importance of evidence-based practice, there is an evidence practice gap that may in part be due to the fact that promoting self-management necessitates change in clinical behaviours. Evidence suggests that a patient's motivation and maintenance of self management behaviours can be positively influenced by the clinician's use of an autonomy supportive communication style. Therefore, the aim of this study was to develop and pilot-test the feasibility of a theoretically derived implementation intervention to support physiotherapists in using an evidence-based autonomy supportive communication style in practice for promoting patient self-management in clinical practice. METHODS: A systematic process was used to develop the intervention and pilot-test its feasibility in primary care physiotherapy. The development steps included focus groups to identify barriers and enablers for implementation, the theoretical domains framework to classify determinants of change, a behaviour change technique taxonomy to select appropriate intervention components, and forming a testable theoretical model. Face validity and acceptability of the intervention was pilot-tested with two physiotherapists and monitoring their communication with patients over a three-month timeframe. RESULTS: Using the process described above, eight barriers and enablers for implementation were identified. To address these barriers and enablers, a number of intervention components were selected ranging from behaviour change techniques such as, goal-setting, self-monitoring and feedback to appropriate modes of intervention delivery (i.e. continued education meetings and audit and feedback focused coaching). Initial pilot-testing revealed the acceptability of the intervention to recipients and highlighted key areas for refinement prior to scaling up for a definitive trial. CONCLUSION: The development process utilised in this study ensured the intervention was theory-informed and evidence-based, with recipients signalling its relevance and benefit to their clinical practice. Future research should consider additional intervention strategies to address barriers of social support and those beyond the clinician level. PMID- 26142485 TI - Comparison of rigid and flexible endoscopy for removing esophageal foreign bodies in an emergency. AB - BACKGROUND/PURPOSE: Despite the effectiveness of endoscopies in removing ingested foreign bodies (FBs) impacted in the esophagus, the merits and limitations of flexible endoscopy (FE) and rigid endoscopy (RE) remain unclear. Therefore, this study compares the advantages and disadvantages of both endoscopic procedures from a clinical perspective. METHODS: A retrospective review was made of 273 patients suspected of esophageal FBs in emergency consultations of a tertiary medical referral center from March 2010 to March 2014. All patients received routine physical examinations, otolaryngological examinations, and X-rays of the neck and chest. The door-to-endoscopy time, procedure time, postendoscopic hospital stay, successful removal rates, and complications were analyzed as well. RESULTS: In this study, the most common esophageal FBs were fish and animal bones (76%) in adults and coins (74%) in children. The patients with existing esophageal FBs had significantly more frequent symptoms of dysphagia and signs of linear opacity as detected with lateral neck radiography than those without FB. Additionally, the door-to-endoscopy time, procedure time, and postendoscopic hospital stay was significantly shorter in FE patients than in RE patients. However, both RE and FE patients had high rates of successful FB removal (95%) and low complication rates (2%). CONCLUSION: Both FE and RE remove esophageal FBs successfully, as evidenced by their high success rates, low complication rates, and high detection rates. Although FE under local anesthesia is a less time consuming procedure for adults, RE under general anesthesia may be preferable for children and can serve as an alternative to FE. PMID- 26142484 TI - PredSTP: a highly accurate SVM based model to predict sequential cystine stabilized peptides. AB - BACKGROUND: Numerous organisms have evolved a wide range of toxic peptides for self-defense and predation. Their effective interstitial and macro-environmental use requires energetic and structural stability. One successful group of these peptides includes a tri-disulfide domain arrangement that offers toxicity and high stability. Sequential tri-disulfide connectivity variants create highly compact disulfide folds capable of withstanding a variety of environmental stresses. Their combination of toxicity and stability make these peptides remarkably valuable for their potential as bio-insecticides, antimicrobial peptides and peptide drug candidates. However, the wide sequence variation, sources and modalities of group members impose serious limitations on our ability to rapidly identify potential members. As a result, there is a need for automated high-throughput member classification approaches that leverage their demonstrated tertiary and functional homology. RESULTS: We developed an SVM-based model to predict sequential tri-disulfide peptide (STP) toxins from peptide sequences. One optimized model, called PredSTP, predicted STPs from training set with sensitivity, specificity, precision, accuracy and a Matthews correlation coefficient of 94.86%, 94.11%, 84.31%, 94.30% and 0.86, respectively, using 200 fold cross validation. The same model outperforms existing prediction approaches in three independent out of sample testsets derived from PDB. CONCLUSION: PredSTP can accurately identify a wide range of cystine stabilized peptide toxins directly from sequences in a species-agnostic fashion. The ability to rapidly filter sequences for potential bioactive peptides can greatly compress the time between peptide identification and testing structural and functional properties for possible antimicrobial and insecticidal candidates. A web interface is freely available to predict STP toxins from http://crick.ecs.baylor.edu/. PMID- 26142486 TI - Association of metabolic syndrome with testosterone and inflammation in men. AB - OBJECTIVE: There is limited data on the assessment of relationship between sex hormones, metabolic syndrome (MS) and inflammation. Therefore, our objective was to examine the relationship between metabolic syndrome, testosterone and inflammation. PATIENTS AND METHODS: It was a cross-sectional study which included 309 subjects in the age range of 30-70years. Blood was analyzed for plasma glucose, serum lipids, total testosterone (TT) and high-sensitivity C-reactive protein (hs-CRP). RESULTS: There were 153 patients with metabolic syndrome and 156 without MS according to modified NCEP guidelines. Age, BMI, obesity, dyslipidaemia, smoking (OR=2.35, CI=1.35-4.09), LDL-Ch, low TT (OR=0.76, CI=0.38 1.52) and elevated hs-CRP (OR=1.56, CI=0.87-2.80) were significant independent predictors of MS (all P<0.05). CONCLUSIONS: The low testosterone and high hs-CRP levels are independent predictors of metabolic syndrome. PMID- 26142487 TI - Design, synthesis and evaluation of new GEQ derivatives as inhibitors of InhA enzyme and Mycobacterium tuberculosis growth. AB - A series of fluorene-based derivatives was synthesized and evaluated for inhibiting both InhA and Mycobacterium tuberculosis growth. These compounds were inspired by the previously reported Genz-10850 molecule, a good InhA inhibitor, but with a poor activity against M. tuberculosis growth. Structure-activity relationships were performed by introducing the following chemical modifications: 1) the piperazine ring; 2) the amide group; 3) the aryl moiety; and 4) the fluorene moiety. Among these new derivatives, one of them was more effective against both the InhA activity and mycobacterial growth, compared to the hit compound. Docking studies were also performed to rationalize activities of these derivatives. Furthermore, we showed for the first time that efflux pump inhibitors potentiated the efficacy of Genz-10850 (GEQ) derivatives against M. tuberculosis growth, demonstrating that these compounds could be substrates of some efflux pumps. PMID- 26142488 TI - Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives. AB - Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importance of H bonding and stacking pi-pi interactions. To improve the readthrough activity we changed the fluorine number and position in the PTC124 fluoroaryl moiety. The readthrough ability of these PTC124 derivatives was tested in human cells harboring reporter plasmids with premature stop codons in H2BGFP and FLuc genes as well as in cystic fibrosis (CF) IB3.1 cells with a nonsense mutation. Maintaining low toxicity, three of these molecules showed higher efficacy than PTC124 in the readthrough of the UGA premature stop codon and in recovering the expression of the CFTR protein in IB3.1 cells from cystic fibrosis patient. Molecular dynamics simulations performed with mutated CFTR mRNA fragments and active or inactive derivatives are in agreement with the suggested interaction of PTC124 with mRNA. PMID- 26142489 TI - Synthesis and anti-metastatic effects of novel chiral ionone alkaloid derivatives. AB - Novel chiral ionone alkaloid derivatives were synthesized and evaluated their anti-metastatic effects in human MDA-MB-231 breast cancer cells. The chiral center C-6 of derivatives exerted an important role in response to the anti metastatic activity. Comparing with a positive control of LY294002, compounds 17b and 19a exhibited potent inhibitory effects on the EGF-induced invasion of MDA-MB 231 cells with IC50 values of 0.026 +/- 0.003 and 0.016 +/- 0.002 MUM, respectively. Moreover, compounds 17b and 19a showed inhibitory effects on the expressions of p-PKCzeta and p-integrin beta1 in MDA-MB-231 cells in a dose dependent manner. Thus, compounds 17b and 19a offer potential to be developed as novel anti-metastasis agents. PMID- 26142490 TI - Hybrid compounds with two redox centres: modular synthesis of chalcogen containing lapachones and studies on their antitumor activity. AB - Chalcogen-containing beta-lapachone derivatives were synthesized using a straightforward methodology and evaluated against several cancer cell lines (leukaemia, human colon carcinoma, prostate, human metastatic prostate, ovarian, central nervous system and breast), showing, in some cases, IC50 values below 1 MUM. The cytotoxic potential of the lapachones evaluated was also assayed using non-tumor cells: human peripheral blood mononuclear cells, two murine fibroblast lines (L929 and V79 cells) and MDCK (canine kidney epithelial cells). These compounds could provide promising new lead derivatives for anticancer drug development. This manuscript reports important findings since few authors have described C-3 substituted beta-lapachone with potent antitumor activity. The methodology employed allowed the preparation of the compounds from lapachol within a few minutes in a green approach. PMID- 26142491 TI - Primaquine-pyrimidine hybrids: synthesis and dual-stage antiplasmodial activity. AB - A series of novel pyrimidine-primaquine hybrids were synthesized and their effectiveness against the blood and liver stages of malaria parasites was evaluated. The hybrids displayed enhanced liver stage in vitro activity against P. berghei liver stage infection. PMID- 26142492 TI - Advances in tetrahydropyrido[1,2-a]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors. AB - An efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine isoindolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSK3 as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84 nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320 nM). Antiproliferative effects on cells were correlated with the in vitro kinase activities and the best effects were obtained with lung and colon cell lines. PMID- 26142493 TI - Truview EVO2 Laryngoscope Reduces Intubation Difficulty in Maxillofacial Surgeries. AB - PURPOSE: Recently, there has been a dramatic increase in the use of the Truview EVO2 for the management of patients with potentially difficult airways. However, the comparison of Truview EVO2 with the classic Macintosh laryngoscope in patients with maxillofacial trauma remains unevaluated. Thus, the purpose of this study was to evaluate and compare the intubation conditions with the Truview EVO2 video laryngoscope and the Macintosh laryngoscope in patients with maxillofacial injury. MATERIALS AND METHODS: Forty-two patients with American Society of Anesthesiologists status I and II requiring nasotracheal intubation for maxillofacial surgery were included in this prospective randomized trial. Anesthesia was induced with fentanyl 2 MUg/kg, propofol 2 to 3 mg/kg, and rocuronium bromide 0.6 mg/kg. Intubation was performed with the Macintosh laryngoscope or the Truview EVO2 video laryngoscope. Comparative data based on the Intubation Difficulty Scale score were assessed as the primary outcome. Laryngoscopic view, time taken for glottis visualization, time taken to pass the endotracheal tube, total time to intubate, and the number of optimizing and hemodynamic variables were recorded as secondary outcomes. RESULTS: The 2 groups were comparable in patient characteristics and preoperative airway assessment parameters. The Intubation Difficulty Scale score was significantly less in the Truview EVO2 group compared with the Macintosh group (mean +/- standard deviation, 0.30 +/- 0.7 vs 1.70 +/- 1.8; P = .002). The Truview EVO2 video laryngoscope required significantly less time for glottic visualization (9.40 +/- 10.9; P = .002). The Truview EVO2 provided a significantly better laryngoscopic view as graded by the percentage of glottic opening and the modified Cormack Lehane grading system compared with the Macintosh laryngoscope (P < .002). The hemodynamic variables, number of optimizing maneuvers, and the incidence of side effects were comparable in the 2 groups. CONCLUSION: The Truview EVO2 performs better than the Macintosh laryngoscope because it considerably decreases the intubation difficulty in patients undergoing maxillofacial surgeries. Therefore, the Truview EVO2 could be a good alternative for managing a difficult airway in patients with maxillofacial injury. PMID- 26142494 TI - Adenosine receptors and diabetes: Focus on the A(2B) adenosine receptor subtype. AB - Over the last two decades, diabetes mellitus has become one of the most challenging health problems worldwide. Diabetes mellitus, classified as type I and II, is a pathology concerning blood glucose level in the body. The nucleoside adenosine has long been known to affect insulin secretion, glucose homeostasis and lipid metabolism, through activation of four G protein coupled adenosine receptors (ARs), named A1, A2A, A2B and A3. Currently, the novel promising subtype to develop new drugs for diabetes treatment is the A2BAR subtype. The use of selective agonists and antagonists for A2BAR subtype in various diabetic animal models allowed us to identify several effects of A2BAR signaling in cell metabolism. In particular, the focus of this review is to summarize the studies on purinergic signaling associated with diabetes through A2BARs modulation. PMID- 26142495 TI - The Temporal Sequence of Social Anxiety and Depressive Symptoms Following Interpersonal Stressors During Adolescence. AB - Social anxiety and depressive symptoms dramatically increase and frequently co occur during adolescence. Although research indicates that general interpersonal stressors, peer victimization, and familial emotional maltreatment predict symptoms of social anxiety and depression, it remains unclear how these stressors contribute to the sequential development of these internalizing symptoms. Thus, the present study examined the sequential development of social anxiety and depressive symptoms following the occurrence of interpersonal stressors, peer victimization, and familial emotional maltreatment. Participants included 410 early adolescents (53% female; 51% African American; Mean age =12.84 years) who completed measures of social anxiety and depressive symptoms at three time points (Times 1-3), as well as measures of general interpersonal stressors, peer victimization, and emotional maltreatment at Time 2. Path analyses revealed that interpersonal stressors, peer victimization, and emotional maltreatment predicted both depressive and social anxiety symptoms concurrently. However, depressive symptoms significantly mediated the pathway from interpersonal stressors, peer victimization, and familial emotional maltreatment to subsequent levels of social anxiety symptoms. In contrast, social anxiety did not mediate the relationship between these stressors and subsequent depressive symptoms. There was no evidence of sex or racial differences in these mediational pathways. Findings suggest that interpersonal stressors, including the particularly detrimental stressors of peer victimization and familial emotional maltreatment, may predict both depressive and social anxiety symptoms; however, adolescents who have more immediate depressogenic reactions may be at greater risk for later development of symptoms of social anxiety. PMID- 26142499 TI - Maternal critical care - time to embrace continuity. PMID- 26142497 TI - Oseltamivir inhibits influenza virus replication and transmission following ocular-only aerosol inoculation of ferrets. AB - Ocular exposure to influenza virus represents an alternate route of virus entry capable of establishing a respiratory infection in mammals, but the effectiveness of currently available antiviral treatments to limit virus replication within ocular tissue or inhibit virus spread from ocular sites to the respiratory tract is poorly understood. Using an inoculation method that delivers an aerosol inoculum exclusively to the ocular surface, we demonstrate that oral oseltamivir administration following ocular-only aerosol inoculation with multiple avian and human influenza viruses protected ferrets from a fatal and systemic infection, reduced clinical signs and symptoms of illness, and decreased virus transmissibility to susceptible contacts when a respiratory infection was initiated. The presence of oseltamivir further inhibited influenza virus replication in primary human corneal epithelial cells. These findings provide critical experimental evidence supporting the use of neuraminidase inhibitors during outbreaks of influenza virus resulting in ocular disease or following ocular exposure. PMID- 26142500 TI - Preliminary assessment of phytochemical contents and antioxidant properties of Pistacia integerrima fruit. AB - Present study was focused on the evaluation of preliminary phytochemical screening and antioxidant properties in hydrophilic and lipophilic solvents extracts of Pistacia integerrima fruit, collected from Lesser Himalayas-Pakistan. Ethnobotanical data were collected through semi-structured interviews. Standard analytical methods were followed to estimate the proximate composition of nutrients, trace metals and phytochemical contents including phenolics, flavonoids, flavonols and ascorbic acid. The free radical scavenging activities of aqueous and acetone extracts were carried out against 2, 2-diphenyl-1 picrylhydrazyl, hydroxyl radical, hydrogen peroxide radical, ferrous ion chelation, ferric ion reduction, and phosphomolybdenium complex assay. Comparatively highest value of cultural importance index was determined for Margalla hills than other study sites. Crude fibers contents (33.65%) were found highest among nutrients, while in minerals utmost level was measured for K (947.3 mg/kg, FW), followed by Ca, Mg, Na and Fe. Acetone extract exhibited highest total phenolics contents (113.7 mg GAE/100g, FW) and antioxidant potential for ferric ion reduction (107.3 MUM GAE/100g, FW), phosphomolybdenum complex assay (99.32 MUM AAE/100g, FW) and DPPH radical scavenging (91.89%). Fruit of P. integerrima was found an excellent source of nutrients, minerals and antioxidants. Crude extracts exhibited noteworthy potential against free radicals and could be of immense significance in the prevention of different diseases related to free radicals. Present data could be an effectual tool for propagation programs intended to enhance the antioxidant and other phytochemical components in foods. PMID- 26142502 TI - Biodistribution and kinetic studies of technetium-99m labeled Naja naja karachiensis venom via gamma scintigraphic and SPECT images. AB - Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio distribution and blood kinetics, venom was labeled with the radiotracer (technetium-99m) by following the method of direct labeling technique. Its maximum labeling percentage was 97.7% (pH 6, 100 ug stannous chloride dihydrate) which was higher than some other reported venom. Radio labeled venom was stable for more than 4 hours both in vivo (96%) and in vitro (serum 94.1%, saline 94.3%) experimentations. Intravenous doses of venom (250 ug, 0.5 mCi) were found to be evenly distributed (having R/L ratio=1.0) in all parts of sacrificed rabbits. Kidneys (53.75% activity/g) and urinary bladder (23.70% activity/g) were found with the copious quantity of injected dose of venom. Rest of all other organs was found with subsequent remaining dose of venom. Among them, lungs (14.2% activity/g), liver (4.32% activity/g), bones (1.38% activity/g), heart (0.8% activity/g), blood (0.56% activity/g), skin (0.45% activity/g), intestines (0.35% activity/g), skeleton muscles (0.3% activity/g), brain (0.14% activity/g) and stomach (0.05% activity/g) are included. After 24 hours of injection, poisoned blood of rabbits was almost cleared from venom. Gamma scintigraphic images (up to 2 hours) along with bio distribution suggest that kidneys are main organs of excretion in rabbits. Elimination started immediately after administration of venom however, possible sites for metabolism of venom are liver and lungs. More accumulation of venom in heart compared to brain suggests its higher affinity (thus possible higher toxicity) to cardiac muscles as compared to brain tissues. PMID- 26142501 TI - Evaluation of putative cytotoxic activity of crude extracts from Onopordum acanthium leaves and Spartium junceum flowers against the U-373 glioblastoma cell line. AB - Crude hydromethanolic (80% methanol) extracts produced by maceration of Onopordum acanthium leaves and Spartium junceum flowers were tested for cytotoxic effects against glioblastoma U-373 tumour cells. Onopordum acanthium extract was found to be ~5 times more cytotoxic than Spartium junceum (IC50 values of 309 and 1602MUg/ml, respectively). Similar to most chemotherapeutic agents killing through the intrinsic pathway, Onopordum killed the cells via apoptosis, which was confirmed by the activation of caspase-3. Spartium exerted its weak cytotoxic effect, presumably by a caspase-independent, non-apoptotic form of necrotic-like programmed cell death. Onopordum acanthium is considered a promising plant for the researchers investigating putative biological activities, particularly antitumour and immune-related activity. PMID- 26142496 TI - Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis. AB - Coxsackieviruses (CVs) are relatively common viruses associated with a number of serious human diseases, including myocarditis and meningo-encephalitis. These viruses are considered cytolytic yet can persist for extended periods of time within certain host tissues requiring evasion from the host immune response and a greatly reduced rate of replication. A member of Picornaviridae family, CVs have been historically considered non-enveloped viruses - although recent evidence suggest that CV and other picornaviruses hijack host membranes and acquire an envelope. Acquisition of an envelope might provide distinct benefits to CV virions, such as resistance to neutralizing antibodies and efficient nonlytic viral spread. CV exhibits a unique tropism for progenitor cells in the host which may help to explain the susceptibility of the young host to infection and the establishment of chronic disease in adults. CVs have also been shown to exploit autophagy to maximize viral replication and assist in unconventional release from target cells. In this article, we review recent progress in clarifying virus replication and dissemination within the host cell, identifying determinants of tropism, and defining strategies utilized by the virus to evade the host immune response. Also, we will highlight unanswered questions and provide future perspectives regarding the potential mechanisms of CV pathogenesis. PMID- 26142503 TI - Antibacterial activity of herbal extracts against multi-drug resistant Escherichia coli recovered from retail chicken meat. AB - Increasing incidence rate of multiple drug resistance in Escherichia coli (E. coli) due to extensive uses of antibiotics is a serious challenge to disease treatment. Contaminated retail chicken meat is one of the major sources of spread of multi drug resistant (MDR) E. coli. Current study has been conducted to study the prevalence of MDR E. coli in retail chicken meat samples from Lahore city of Pakistan and it was found that 73.86% of E. coli isolates have MDR pattern. In vitro evaluation of antibacterial activity of crude ethanolic extracts of six herbs against MDR E. coli phenotypes has revealed that clove and cinnamon have maximum zones of inhibition as compared to other herbal extracts. Mint and coriander gave the intermediate results while garlic and kalonji showed the least antibacterial activity against the MDR E. coli phenotypes using the agar well diffusion technique. Average Minimum Inhibitory Concentrations (MICs) for clove, mint, cinnamon, coriander, kalonji and garlic extracts were 1.15, 1.38, 0.5, 1.99, 2.41, 8.60 mg/mL respectively using the broth micro dilution method. The results obtained in present study were revealed that crude ethanol extracts of selected herbs have had significant antibacterial activity. Hence they can be used as promising alternatives of antimicrobials against MDR E. coli species and can be used for cooked food preservation. PMID- 26142504 TI - The detection of YMDD mutation of hepatitis B virus by allele-specific PCR and a cross-contamination proofed device. AB - Lamivudine (LAM) is commonly used to treat Hepatitis B virus (HBV) infection, but its use frequently induces drug resistance. Therefore, rapid and correct detection of drug-resistant HBV is important for effective treatment of HBV infection. In this study, we aimed to develop a novel, simple, and user-friendly method for the detection of LAM resistant HBV. Samples were collected from 60 HBV infected patients for the analysis by allele-specific polymerase chain reaction (AS-PCR), nucleic acid detection strip (NADS) and a cross-contamination proofed device. HBV YMDD mutations were detected by AS-PCR, restriction fragment length polymorphism (RFLP) and DNA sequencing. A 91.7% concordance between all three methods was obtained. Compared to sequencing and RFLP, AS-PCR detected more samples with mutant variants and was more sensitive. This novel method had a detection limit of approximately 103 copies/ml and detected a variant of only 5% of total HBV population. In conclusion, we develop a new assay which could be useful for the detection of HBV LAM resistance, especially in resource-poor settings. PMID- 26142505 TI - Plasmid borne BAC-IB17: Localization of a potential antibacterial positive marker (Bac+) encoded broad inhibitory spectrum bacteriocin. AB - Production of antimicrobial compounds is considered as ubiquitous anti-competitor strategy in bacterial ecosystem. Bacteriocins are heterogeneous; highly specific and efficient anti-competitor agents and the gene responsible for the production of bacteriocins mostly exist in an autosomal state and associated with plasmids. BAC-IB17 is a broad spectrum bacteriocin and its production was observed at different stages of the growth cycle from Bacillus subtilis KIBGE-IB17. Growth kinetics of B. subtilis KIBGE-IB17 along with the production of BAC-IB17 showed that it exhibited secondary metabolite kinetics. Plasmid curing technique revealed that the gene responsible for the bacteriocinogenecity in B. subtilis KIBGE-IB17 was located on the plasmid of the bacterium. Overlay method also demonstrated the plasmid-mediated bacteriocinogenesis of the isolated colonies. With the advancement in genomics and proteomics, the plasmid borne BAC-IB17 can play a significant role in the transfer of bacteriocinogenic factor to other incompetent cells and also in the maintenance of plasmid in bacterial population. PMID- 26142506 TI - Determination of Cefadroxil in Tablet/Capsule formulations by a validated Reverse Phase High Performance Liquid Chromatographic method. AB - An innovative, selective and rapid reversed phase High Performance Liquid Chromatographic (RP-HPLC) method for the analysis of cefadroxil in bulk material and oral solid dosage forms has been developed and validated. The chromatographic system consisted of Sil-20A auto sampler, LC-20A pump and SPD-20A UV/visible detector. The separation was achieved by C18 column at ambient temperature with a mobile phase consisting of methanol: Phosphate buffer (10: 90) at a flow rate of 1.5 ml/min. The method is reproducible, repeatable (%RSD for intra-day and inter day ranged between 1.75-5.33% and 0.58-2.69%) and linear (R2=0.9935). The LOD and LOQ of the method were 0.5 and 1.0 MUg/ml, respectively. The present RP-HPLC method was found to be sensitive, accurate, precise, rapid and cost effective that can be efficiently used in QC/QA laboratories for routine analysis of the raw materials as well as oral dosage formulations of cefadroxil. PMID- 26142507 TI - Report: Central nervous system (CNS) toxicity caused by metal poisoning: Brain as a target organ. AB - People relate the neural disorders with either inheritance or psychological violence but there might be some other reasons responsible for the ailment of people that do not have such a background. The present study explains the chronic effect of heavy toxic metals on nervous system. During experimentation, rabbits used as laboratory animals, were given test metals in their diet. Concentration of metals given to them in the diet was less than their tolerable dietary intake. Behavioral changes were observed during experimentation. Periodic increase in the metal concentration was seen in the blood sample of rabbits. They were slaughtered after a period of eight months of slow poisoning. Histological examination of brain tissues was performed. The brain samples were analyzed by Atomic absorption spectroscopy and Inductively Coupled Plasma Mass Spectrometry to find the retention of heavy metals in mammalian brain. Concentration of lead, mercury and cadmium in the blood samples of occupationally exposed people and patients with neurological disorders at the time of neurosurgery was determined by using the same techniques. During circulation, toxic metals passes through the nerve capillaries to settle down in the brain. Heavy metals cross the blood brain barrier and 'may retain themselves in it. Brain tumors and biopsy samples of patients with neurological disorder were also analyzed to relate neurotoxicity and heavy metal poisoning. Results obtained shows that lead, mercury and cadmium retain themselves in the brain for longer period of time and are one of the causes of neurotoxicity. PMID- 26142508 TI - Biological activities of Morus celtidifolia leaf extracts. AB - The aims of this research were to examine the antibacterial, cytotoxic and antiradical/antioxidant activities of the organic extracts obtained from the leaves of the medicinal plant Morus celtidifolia (Family: Moraceae). To evaluate its antimicrobial properties, M. celtidifolia was tested against the bacteria of medical importance: Bacillus subtilis, Staphyloccocus aureus, Enterococcus faecalis, Escherichia coli, Enterobacter cloacae and Enterobacter aerogenes. Cytotoxic activity was assessed by using the brine shrimp (Artemia salina) lethality assay and also by toxicity screening against human cancer cell lines: MCF-7 (human breast adenocarcinoma) and HeLa (cervix adenocarcinoma). The free radical-scavenging activity was determined by the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Results revealed that the hexanic extract has antibacterial activity only against Gram positive strains, while the methanolic extract showed better cytotoxic and antioxidant activities than the non- polar extract with a median lethal dose (LD50) of 125MUg/ml, 90MUg/ml and 75MUg/ml against A. salina, MCF-7 and HeLa cells respectively, and median effective concentration (EC50) of 152MUg/ml on radical scavenging assay. This is the first study reporting the biological activities of leaves of Morus celtidifolia. PMID- 26142509 TI - Behavioral deficits in rats following acute administration of glimepiride: Relationship with brain serotonin and dopamine. AB - A considerable body of literature suggests that depression and diabetes mellitus are co-morbid. The present study was designed to test any possible behavioral deficits and/or neurochemical changes in the brain as induced by the anti diabetic drugs. Twenty-four rats were divided into four groups: (i) saline (ii) glimepiride (2.5mg/kg)- (iii) glimepiride (5.0mg/kg)- and (iv) glimepiride (10 mg/kg) injected animals. Behavioral activities in Skinner's box, open field and elevated plus maze were monitored 20, 35 and 45 minutes post injection respectively. Animals were decapitated 60 minutes post injection to collect brain samples. Samples were kept at -70 degrees C until neurochemical analysis by HPLC EC. Results from the present study show decreased time spent in the open arm of the elevated plus maze (p<0.05) at all the three doses. A decrease in the HVA (Homovanillic acid) levels at all three doses (p<0.01) was also observed along with decreased 5-HT (5-Hydroxytryptamine) (p<0.05 at 5.0 and 10mg/kg) and 5-HIAA (5-Hydroxyindoleacetic acid) (p<0.05 at all three doses) levels. Since a decrease in 5-HT metabolism can induce depression-like effects, the present study therefore suggests that the occurrence of depression in diabetic patients is due to the use of glimipride. Effects of long-term administration of smaller doses of glimipride are to be explored further to monitor tolerance in glimipride-induced deficits of serotonin. The finding may help to explore the cause of depression in diabetics for improving pharmacotherapy in diabetes. PMID- 26142510 TI - Design and content determination of nimesulide injectable formulation. AB - The aim of the present study was to formulate Nimesulide inject able solution, establish a method for content determination, and accumulate data for registration of a new Nimesulide formulation. The optimal Nimesulide inject able formulation was determined based on the results of single factor test and orthogonal test. Moreover, clarity, stability, pH, content and related substances of Nimesulide were used as the main study indicators. The content of Nimesulide in inject able solution was determined by the high performance liquid chromatography (HPLC) method. The mobile phase consisted of V (methanol): V (potassium dihydrogen phosphate, pH 4.2)=60:40 at a flow rate of 1.0 mL/min. The detection was carried out with UV detector (lambda(max) =254 nm) under a column temperature of 25 degrees C and an injection volume of 20MUL. The optimal inject able formulation was 4% Nimesulide, 4% ethanolamine, 0.1% L-cysteine, 0.01% EDTA 2Na, a suitable amount of lactic acid and water for injection. Nimesulide detection limits range from 20 to 80 MUg/mL with a correlation coefficient of 0.9995 and high average recovery 99.91% (RSD=0.06%). In conclusion, the formulation was suitable for Nimesulide inject able form, and the determination method was simple, sensitive and accurate. Therefore, the Nimesulide inject able formulation can be used for industrial production and effectively controlled. PMID- 26142511 TI - Proximate and elemental analysis of five selected medicinal plants of family Solanaceae. AB - The proximate analysis revealed the presence of ash, moisture, protein, fiber, fats and carbohydrate. ANOVA showed that ash and moisture contents was non significant between the plant parts and phenological stages. Crude protein was non significant between the plant parts and phenological stages except for Datura innoxia parts but not for its phenolgical stages, while crude fats were non significant between the plant parts and phenological stages except for Solanum nigrum and Solanum surattense parts but not for their phenolgical stages. Crude fiber was non significant between the plant parts and phenological stages except for Datura innoxia parts but not for its phenolgical stages. And carbohydrates was non significant between the plant parts and phenological stages except for the phenolgical stages of Solanum surattense and Withania coagulans. The mineral analysis showed the presence of Cr, Zn, Cu, Mn, Fe, Ca, K, Mg and Na in the roots, stems, leaves, flowers and fruits of the plants in three different phenological stages. Only the micro-minerals were present in traces while the macro-minerals were present high quantities as compared to the micro-minerals. PMID- 26142512 TI - Comparative study of antioxidant, metal chelating and antiglycation activities of Momordica charantia flesh and pulp fractions. AB - Momordica charantia is commonly used as a vegetable and folk medicine in most parts of South Asia. This study aims to determine and compare the antioxidant, metal chelating and antiglycation activities of aqueous extracts of M. charantia fruit flesh (MCF) and fruit pulp (MCP) fractions. Our results show that MCP has pronounced DPPH and ABTS radical scavenging potential compared to MCF. In the antiglycation assay both fractions illustrated considerable inhibitory activities against the formation of AGEs induced by glucose with an efficacy of 75 and 67% with 150 MUl of MCP and MCF extracts respectively, almost equal to 0.3mM amino guanidine. Results for metal catalysed protein fragmentation and autoxidative and glycoxidation assays demonstrate that MCF and MCP inhibited metal catalysed protein fragmentation. The percentage of relative standard deviation for three replicate measurements of 150 MUl of MCF and MCP was < 3.0% for antiglycation. The antioxidant assays with regression values of MCP (0.981 and 0.991) and MCF (0.967 and 0.999) were also recorded. We conclude that both extracts possess high antioxidant and antiglycation activities and are equally good sources of antioxidant and antiglycating agents. PMID- 26142513 TI - Larvicidal, insecticidal, brine shrimp cytotoxicity and anti-oxidant activities of Diospyros kaki (L.) reported from Pakistan. AB - Diospyros kaki is cultivated in different agro-ecological zones of Pakistan, especially in Malakand division. The current study was designed to investigate the hide potential of the vulnerable species of the plant. Aqueous extracts of Diospyros kaki leaves were screened for larvicidal, insecticidal cytotoxic and antioxidant activities. The extract exhibited moderate to outstanding larvicidal activity (100 to 28%) at 100, 80, 70, 50, 40, 30, 20 and 10% concentrations respectively after 24 hours, showing 42% LC50. Permitrin displayed 100% lethality at 0.3%. The extract demonstrated outstanding cytotoxic action against brain shrimps nauplii (Artemia salina), showing 10 ppm LC50 which is closed to the LC50 (9.8MUg/ml) of standard drug Etoposide. Similarly profound insecticidal potential (100%) was recorded after 15 min against Cimex lectularius. In DPPH scavenging activity the extract demonstrated moderate 30.22%, while Quercetin, Gallic acid and Acetic acid showed 98, 96 and 97% activity respectively at 100 ppm. Thus on the basis of our finding it could be concluded that the decoction of the leaves of D. kaki is a good natural alternative for the control of insects and neoplasia. PMID- 26142514 TI - Evaluation on bioactivities of total flavonoids from Lavandula angustifolia. AB - Lavandula angustifolia was used to treat flus and fevers, joint swelling and pain in Uighur medicine. This study aimed to investigate antioxidant, antit anti inflammatory and antalgic noids content (530.1mg/g rutin/g dry extract) with stronger DPPH scavenging abilities and reduciactivities of total flavonoids from Lavandula angustifolia (LTF). Results indicated that LTF possesses the highest total flavong power. Some flavonoids separated from LTF, and their DPPH scavenging abilities as follows: rosmarinic acid (2, near to Vit C) >luteolin (3) >apigenin (4) >luteolin 7-O-beta-D-glucoside (5) >apigenin 7-O-beta-D-glucoside (6) >luteolin 7-O-beta-D-glucuronide (7). LTF significantly decreased malondialdehyde (MDA) level in D-galactose induced aging model compared to the control group (P<0.05), as well as significantly increased plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (P<0.05). Moreover, 17.4, 34.8 and 69.6 mg/kg doses of LTF were exhibited significant analgesic and anti-inflammatory activities in a dose dependent manner (P<0.05). Cytotoxicity of LTF on Bel-7402 and Hela cell lines were showed by MTT assay also. These results verified traditional usage of this plant and suggested also that LTF is worth developing and studying further. PMID- 26142515 TI - Analyses of bile from gallbladders of Arius platystomus, Arius tenuispinis, Pomadasys commersonni and Kishinoella tonggol. AB - Bile from gallbladders of Arius platystomus (Singhara), Arius tenuispinis (Khagga), Pomadasys commersonni (Holoola) and Kishinoella tonggol (Dawan) were derivatised and analysed by GC-MS for identification of bile acids and bile alcohols. Cholic acid and Chenodeoxycholic acid were found as major bile acids in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Other bile acids identified in Arius platystomus were allochenodeoxycholic acid, allodeoxycholic acid, 3alpha,7alpha,12alpha-trihydroxy-24-methyl-5beta-cholestane-26-oic acid, and 3alpha,7alpha,12alpha, 24-tetrahydroxy-5alpha-cholestane-26-oic acid. Cholesterol was found as major bile alcohol in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Cholic acid was the major bile acid identified in the bile of Kishinoella tonggol while other bile acids included 3alpha,7alpha,12alpha-tridydroxy-5alpha-cholestanoic acid and 3alpha,7alpha,12alpha-tridydroxy-5beta-cholestanoic acid. Bile alcohol 5beta cyprinol was present in significant amounts with 5beta-cholestane 3alpha,7alpha,12alpha,24-tetrol being the other contributors in the bile of Kishinoella tonggol. PMID- 26142516 TI - Serotonergic activity and hypothalamic-pituitary-adrenal axis response in alcohol administered and subsequently withdrawn rats. AB - Present study aims to depict the role of serotonergic pathways in discrete brain areas (hypothalamus, amygdala, and hippocampus) and their interaction with hypothalamic pituitary adrenal (HPA) axis in alcohol dependence and subsequent withdrawal syndrome in rats. Albino Wistar rats were fed a liquid diet containing alcohol for 4 weeks. Matched control rats were fed isocaloric amounts of the alcohol-free liquid diet, in which the alcohol contribution was substituted with maltose-dextrin. Brain regional tryptophan, 5-hydroxytryptamine (5-HT), 5 Hydroxyindoleacetic acid (5-HIAA) concentrations were determined using high performance liquid chromatography with flourimetric detector. Serum corticosterone was determined spectrofluorimetrically. Data analysis showed that there was significant increase in tryptophan (hippocampus), 5-HT (hippocampus and amygdala) and 5-HT turnover in all the three regions examined when alcohol administered rats were compared with matched controls. In contrast withdrawal from alcohol decreased brain tryptophan, 5-HT and its turnover. It is concluded that the prolong alcohol use boost functions of serotonergic neuronal pathways, in particular, hypothalamus that regulate HPA-axis function and develop tolerance and adaptation. In addition, withdrawal from alcohol exacerbates serotonergic functions that results in failure to suppress corticosterone levels and hence induce low mood states and other signs and symptoms of alcohol withdrawal syndrome. PMID- 26142517 TI - Cardioprotective effect of Thymoquinone: A constituent of Nigella sativa L., against myocardial ischemia/reperfusion injury and ventricular arrhythmias in anaesthetized rats. AB - Reperfusion of the ischemic myocardium causes the myocardial injury and life threatening ventricular arrhythmias in human. This study aimed to investigate the effects of thymoquinone (TQ) on myocardial ischemia/reperfusion (I/R) injury and ischemia- and reperfusion-induced ventricular arrhythmias in anaesthetized rats. Adult male Wistar albino rats were divided into two groups, each containing a control and TQ-treated subgroups. In group I, the myocardial infarct size was determined by triphenyl tetrazolium chloride staining following 2-h reperfusion preceded by 30 min of ischemia. In group II, a 6-min myocardial ischemia was followed by a 10-min reperfusion. TQ-treated subgroups were treated with TQ (10 mg/100 MUl/kg, i.p.) and the control subgroups were treated with the vehicle (100 MUl/kg, i.p.) 20 min prior to the ischemic period. Ischemia was induced by ligating the left main coronary artery, followed by reperfusion. TQ treatment reduced the infarct size (15 +/- 4% versus 69 +/- 6%, P<0.01). Pretreatment with TQ decreased arrhythmia scores, as well as the incidence of ventricular tachycardia and the incidence of ventricular fibrillation during the reperfusion period (arrhythmia scores: 1.4 +/- 0.3 versus 4.4 +/- 0.3, P<0.01). These results suggest that TQ confers protection against myocardial I/R injury and suppresses reperfusion-induced arrhythmias. PMID- 26142518 TI - Detection of Mycobacterium tuberculosis and Mycobacterium bovis from human sputum samples through multiplex PCR. AB - Tuberculosis (TB) has a long history and being present even before the start of recording history. It has left detrimental effects on all aspect of the life and geared the developments in the science of health. TB is caused by Mycobacterium tuberculosis complex (MTBC) including five species M. tuberculosis, M. bovis, M. africanum, M. canetti, and M. microti. M. tuberculosis and M. bovis infect both animals and humans. Therefore, differentiation of these two closely related species is very important for epidemiological and management purpose. We undertook the present study to characterize mycobacteria isolated from sputum of known TB patients by conventional methods and further, by multiplex PCR (mPCR) to detect the prevalence of Zoonotic TB (TB caused by M. bovis). Sputum samples from TB patient were collected from two tertiary care hospitals in Peshawar i.e. Lady Reading Hospital and Hayatabad Medical Complex. All the samples were subjected to Ziehl Neelsen (ZN) stain, culture on Lowenstein Jensen (LJ) and Stone Brink medium, Nitrate reduction test and multiplex PCR. A total of hundred mycobacterial strains were isolated from these samples on the basis of ZN staining, cultural and biochemical methods. Later on, these isolates were subjected to multiplex PCR by using pncATB-1.2 and pncAMT-2 primers specific to M. tuberculosis and JB21, JB22 primers specific to M. bovis. By means of conventional method, these hundred cultures isolates were differentiated into M. tuberculosis (ninety six) and M. bovis (four). Furthermore, by mPCR, it was determined that out of hundred isolates, ninety-eight were identified as M. tuberculosis and two isolates as M. bovis. This molecular method enables to differentiate M. bovis from M. tuberculosis in human sputum. PMID- 26142519 TI - Application of BY-2 cell model in evaluating an effect of newly prepared potential calcium channel blockers. AB - Calcium channel blockers represent a group of therapeutically important compounds that have found an application in treatment of systemic vascular resistance and arterial pressure, eventually angina pectoris. We studied possibility of application of a BY-2 cell model to evaluate the potential of newly prepared potential calcium channel blockers. In the preliminary experiment, toxicity of studied compounds was determined. In the next experiment, we evaluated possible protective effect of studied compounds on programmed cell death induced by hydrogen peroxide on the BY-2 cells. Calcium channel blocker lanthanum ions and imidazole, inhibitor of NAD(P)H oxidase (EC 1.6.3.1) that prevents reactive oxygen species formation and programmed cell death, were used as reference compounds to compare the effect of studied compounds. We studied changes in the cell viability and growth as well as markers of cell proliferation, levels of intracellular free calcium ions, reactive oxygen species, lipid peroxidation, and markers of programmed cell death, mitochondrial membrane potential and caspase like activity. Late signs of programmed cell death (changes in nuclear architecture) were also evaluated. Our experiments revealed protective potential of studied compounds against programmed cell death induced by hydrogen peroxide and possibility of application of the BY-2 cell culture to evaluate pharmacological effects of studied compounds in preliminary tests. PMID- 26142520 TI - Generation of recombinant bioluminescent Escherichia coli for quantitative determination of bacterial adhesion. AB - Bacterial adhesion to urinary catheter was evaluated by measuring the light emitted from a recombinant bioluminescent glycocalyx producer Escherichia coli strain. Generation of the bioluminescent strain was carried out by transforming the bacterial cells with pUCP18-GFP plasmid that contains a green fluorescence gene. Light emission measurement was closely correlated with the number of the adherent cells, giving a detectable signal from 1.2 X 102 cells. The efficiency of this assay was confirmed by testing the antiadherent effect of subinhibitory concentrations of ciprofloxacin with the aid of a model for in-vitro catheter colonization. There was no significant difference in the percentage reduction of adherent cells obtained by both light emission measurement and viable cell count techniques. PMID- 26142521 TI - Synthesis, antimicrobial and antifungal possessions of tramadol esters: In vitro studies. AB - Tramadol esters were prepared by refluxing equimolar concentration of tramadol with leucine and asparagine separately with methanol, sulphuric acid and phthalic anhydride for 10 hours and temperature was maintained at 75 degrees C. After refluxing, the colour of sample solutions were changed from colorless to yellow, blank solution was prepared in the same way as the sample solution except the Tramadol. Both the products and blank were neutralized with sodium carbonate and excess of sodium bicarbonate was precipitated as sodium sulphate, which was washed with acetone. The structures of both the products were confirmed with spectral data (FT-IR, 1HNMR and 13CNMR). Antimicrobial and anti-fungal property of derivative of analgesic tramadol drug was tested with one fungus and three sensitive bacteria belonging to both gram positive and gram-negative types. Esterified product of tramadol with leucine and asparagine showed moderate activity against Escherichia coli and Tricophyton rubrum. Both the products showed marked activity against Staphylococcus aureus and found no activity against Salmonella spp. PMID- 26142522 TI - Determination of S- and R-warfarin enantiomers by using modified HPLC method. AB - Warfarin is a commonly prescribed anticoagulant existing in two enantiomeric forms S- and R-warfarin. Many techniques have been used to analyze warfarin in plasma but less frequently for enantiomeric analysis. One of the HPLC method employed was further simplified and made economical. Method was validated according to ICH guidelines and was found to be sensitive, reliable and less time consuming. For both enantiomers, LLOQ was 12.5 ng/mL. The CV% and accuracy for method were in the range of 0.8-14.6% and 92-107% respectively. The recoveries for both enantiomers were in the range of 86-103.8%. Blood samples were collected from 170 stable patients taking warfarin and S- and R-warfarin levels were determined by this method. Majority of subjects were found to have S/R-warfarin ratio of about 1:2 as reported in previous studies due to rapid clearance of S enantiomer than R-enantiomer. However individual subjects data was suggestive of presence of slow metabolizers of S-warfarin leading to altered S/R ratio. Previous studies have also pointed out CYP2C9 polymorphism being responsible for such inter-individual differences in S-warfarin metabolism. So plasma warfarin S/R ratio may serve as a useful phenotypic test for CYP2C9 polymorphism. PMID- 26142523 TI - Simultaneous spectrophotometric determination of the three structural isomers of cresol using multivariate regression methods. AB - The simultaneous determination of the structural isomers of cresol was carried out using UV spectrophotometry by applying the principle component regression (PCR) and partial least squares (PLS) regression methods. Different concentration levels of cresol isomers were determined in their mixtures by construction of a partial factorial calibration design at four levels. Both multivariate calibration models were constructed using the correlation between the concentration and absorbance data matrices in the spectral region 283-305 nm. The methods were validated by analyzing an independent validation set solutions of the same compounds. The methods were found to be accurate and precise as indicated by the mean % recovery (99.96-100.41%) and % relative standard deviation (0.15-0.72%), respectively. The methods were applied to the determination of cresol isomers in a topical veterinary preparation. The methods were proved to be applicable to the determination of the three cresol isomers without prior separation procedures, despite of the extensive spectral overlap of such compounds. PMID- 26142524 TI - Therapeutic intervention and molecular characterizations of bacteriocin producing Lysinibacillus sp., nov., isolated from food sample. AB - Many bacteriocins from Lactobacilli have been reported as immunostimulatory, preservatives, anticancerous and biocontroling. However, antimicrobial potential of Lysinibacillus is not much reported. In this study, an attempt was made to isolate and anticipate therapeutic potential of Lysinibacillus from spoiled food sample. We screened 125 Lactobacilli for their antagonistic nature against food borne and disease causing bacterial and fungal pathogens. Among them, one Bacillus was phenotypically, and 16S rRNA based, molecularly identified as Lysinibacillus species given with accession numbers JX416855 in NCBI. The type strain JX416855 has shown the 99% identity with the Lysinibacillus fusiformis, Lysinibacillus sphaericus and Lysinibacillus xylanilyticus. It was amylase, protease, gelatinase, nitrate reductase and urease negative and catalase positive. The growth conditions and bacteriocin activity were found optimum with MRS media at pH 7-10, Temp-35-40 degrees C and salt tolerance at 1-3% which was optimized with MRS broth at pH 7.4, 37 degrees C, 1.5% NaCl for 48 h in shaking conditions @ 100 rpm. The isolate showed broad-spectrum antibacterial activity against gram positive (10-13 mm) and gram-negative (20mm) bacteria. It also strongly inhibited to fungus Aspergillus, Fusarium and Trichoderma. Bacteriocin from 60% ammonium sulphate fraction strongly inhibited to gram-negative R. planticola and Pseudomonas aeruginosa, which showed three protein bands of high molecular weight (nearly 40-70 kD) by SDS-PAGE analysis. PMID- 26142525 TI - Warfarin use and dose adjustment in a patient with mitral valve replacement. AB - Warfarin is an anticoagulant suppressing the synthesis of the specific vitamin K dependent coagulation factors II, VII, IX and X as well as two vitamin K dependent plasma proteins C and S. Warfarin therapy may bring about severe consequences including warfarin embryopathy associated with maternal warfarin ingestion, warfarin resistance, excessive anticoagulation and warfarin reversal. A 51-year-old female patient experienced warfarin resistance as well as subsequent excessive coagulation and warfarin reversal. With regulation of warfarin dosage and close monitoring of the international normalized ratio, she eventually obtained a proper target international normalized ratio with stable warfarin dose. The patient was more likely to have an acquired warfarin resistance. To regulate dietary habit might be a good solution for the resistance to this drug. In addition, individualized regimen for warfarin use should be established based on the conditions of individual patient including patient's age, gender, body surface area, dietary habit and target international normalized ratio, etc. PMID- 26142526 TI - Borneol inhibits TRPA1, a proinflammatory and noxious pain-sensing cation channel. AB - Borneol, a natural product isolated from several species of Artemisia, Blumea and Kaempferia, has a widespread use in traditional medicine. TRP ion channels are a class of nonselective cation channel proteins involved in a variety of physiological and pathological processes in mammals. TRPA1, a member of TRP family of cation channels, is involved in plethora of processes including noxious cold, noxious-pain sensations, inflammation and the detection of irritant chemicals. Borneol is chemically related to camphor (a known inhibitor of TRPA1 ion channels); therefore, it is beneficial to investigate the effects of borneol on TRPA1. In the present investigation it was found that borneol inhibits TRPA1 mediated cationic currents in low millimolar range (IC50 0.3mM) in heterologous expression systems like Xenopus oocytes and in neurons cultured from trigeminal ganglia. Effects of nicotine, a known chemical irritant and agonist of TRPA1 are also inhibited by borneol in both systems. It is concluded that borneol, being an inhibitor of TRPA1, could be a safer therapeutic-combination in clinical situations where TRPA1 channelopathies like neuropathic-pain, trigeminal neuralgia or nicotine withdrawal treatments are involved. PMID- 26142527 TI - Immobilization-induced increases of systolic blood pressure and dysregulation of electrolyte balance in ethanol-treated rats. AB - Clinical and experimental studies revealed that alcohol drinking and life event stresses are predisposing factors to hypertension. Intra and extra cellular levels of electrolytes may play important role in the pathogenesis and treatment of hypertension. Dietary intake of sodium, potassium, calcium and magnesium is suggested to have a role in the regulation of blood pressure. The present study was designed to monitor the effects of acute exposure to 2h immobilization stress and ethanol administration at a dose of 2.5 g/kg body weight (i.p.) and combined effect of acute administration of ethanol and immobilization stress on systolic blood pressure (SBP), intraerythrocyte, serum and tissue electrolytes in rats. Results showed that acute exposure to 2h immobilization increased SBP, intraerythrocyte sodium and decreased intraerythrocyte potassium in water as well as in ethanol injected rats. The concentration of Na+ and Ca2+ increased while that of K+ and Mg2+ decreased in the heart and kidney tissue. Ethanol administration also increased Na+ and Ca2+ levels and decreased K+ and Mg2+ levels in the heart and kidney tissue. Restraint stress decreased serum levels of Na+, K+, Ca2+, P, and Cl- and increased serum Mg2+, glucose and haematocrit. Ethanol administration also decreased serum levels of Na+, K+, Ca2+, P, and Cl- and increased serum Mg2+, glucose and haematocrit. The effects of ethanol and stress on the changes of blood and tissues electrolytes were additive and may be involved in the greater occurrence of hypertension in alcoholics. Our results suggested an important role of intra and extra cellular electrolytes in both stress and ethanol-induced hypertension. The findings may help to develop strategies for the treatment of hypertension in alcoholics. PMID- 26142528 TI - Formulation and optimization of gastric floating drug delivery system using Central composite design and its biopharmaceutical evaluation. AB - The present work investigates the formulation and biopharmaceutical estimation of gastric floating drug delivery system (GFDDS) of propranolol HCl using semi synthetic polymer carboxymethyl ethyl cellulose (CMEC) and a synthetic polymer polyethylene oxide (PEO). A central composite design was applied for optimization of polymer quantity (CMEC or PEO) and sodium bicarbonate concentration as independent variables. The dependent variables evaluated were: % of drug release at 1 hr (D1hr), % drug release at 3 hr (D3hr) and time taken for 95% of drug release (t95). Numerical optimization and graphical optimization were conducted to optimize the response variables. All observed responses of statistically optimized formulations were in high treaty with predicted values. Accelerated stability studies were conducted on the optimized formulations at 40 +/- 2 degrees C/75% +/- 5% RH and confirm that formulations were stable. Optimized formulations were evaluated for in vivo buoyancy characterization in human volunteers and were found buoyant in gastric fluid. Gastric residence time was enhanced in the fed but not the fasted state. The optimized formulations and marketed formulation were administered to healthy human volunteers and evaluated for pharmacokinetic parameters. Mean residence time (MRT) was prolonged and AUC levels were increased for both optimized floating tablets when compared with marketed product. High relative bioavailability obtained with optimized gastric floating tablets compared to commercial formulation, indicated the improvement of bioavailability. PMID- 26142529 TI - The safety and efficacy of 3% Cannabis seeds extract cream for reduction of human cheek skin sebum and erythema content. AB - Escalated sebum fabrication is seen with an unattractive look and adds to the growth of acne. We aimed to investigate the efficacy and safety of 3% Cannabis seeds extract cream on human cheek skin sebum and erythema content. For this purpose, base plus 3% Cannabis seeds extract and base (control) were prepared for single blinded and comparative study. Healthy males were instructed to apply the base plus 3% Cannabis seeds extract and base twice a day to their cheeks for 12 weeks. Adverse events were observed to determine skin irritation. Measurements for sebum and erythema content were recorded at baseline, 2nd, 4th, 6th, 8th, 10th and 12th week in a control room with Sebumeter and Mexameter. Base plus 3% Cannabis seeds extract was found to be safe in volunteers. Measurements demonstrated that skin sebum and erythema content of base plus 3% Cannabis seeds extract treated side showed significant decrease (p<0.05) compared with base treated side. Base plus 3% Cannabis seeds extract showed safety. It was well tolerated for the reduction of skin sebum and erythema content. Its improved efficacy could be suggested for treatment of acne vulgaris, seborrhea, papules and pustules to get attractive facial appearance. PMID- 26142530 TI - Regulation of ROS defense system by Hybanthus enneaspermus in CCl4 induce cardiac damage. AB - The purpose of this study is to regulate the ROS (Reactive oxygen species) defense system in cardiac damage induced by CCl4(Carbon tetra chloride) in rats using Hybanthus enneaspermus. Administration of CCl4induces damage in the heart of rats as proved by estimation of antioxidant enzymes such as, SOD (Superoxide dismutase), CAT (catalase), GPx (Glutathione Peroxdiase), GR (Glutathione Reductase), GST (Glutathione-S-Transferaes). However, treatment with HEE in CCl4intoxicated rats was found to be protected the heart, as indicated by the enzyme level in serum. A significant increment of serum enzymes level such as SOD, CAT, GPx, GR and GST were observed following HEE treatment during CCl4intoxication whereas MDA (Malondialdehyde) level in HEE treated rats were decreased. The results of our experiment suggest that the treatment of HEE may be the critical remedy for the adverse effect of CCl4in heart function. PMID- 26142531 TI - Report: Bioconversion of agriculture waste to lysine with UV mutated strain of brevibacterium flavum and its biological evaluation in broiler chicks. AB - Lysine executes imperative structural and functional roles in body and its supplementation in diet beneficial to prevent the escalating threat of protein deficiency. The physical mutagenesis offers new fascinating avenues of research for overproduction of lysine through surplus carbohydrate containing agriculture waste especially in developing countries. The current study was aimed to investigate the potential of UV mutated strain of Brevibacterium flavum at 254 nm for lysine production. The physical and nutritional parameters were optimized and maximum lysine production was observed with molasses (4% substrate water ratio). Moreover, supplementation of culture medium with metal cations (i.e. 0.4% CaSO4, 0.3% NaCl, 0.3% KH2PO4, 0.4% MgSO4, and 0.2% (NH4) 2SO4w/v) together with 0.75% v/v corn steep liquor significantly enhanced the lysine production up to 26.71 +/ 0.31 g/L. Though, concentrations of urea, ammonium nitrate and yeast sludge did not exhibit any profound effect on lysine production. Biological evaluation of lysine enriched biomass in terms of weight gain and feed conversion ratio reflected non-significant difference for experimental and control (+ve) groups. Conclusively, lysine produced in the form of biomass was compatible to market lysine in its effectiveness and have potential to utilize at commercial scale. PMID- 26142532 TI - Report: In vivo anticoccidial effects of Azadirachta indica and Carica papaya L. with salinomycin drug as a dietary feed supplement in broiler chicks. AB - A total of thirty suspected broiler chicks were screened for coccidiosis, of them 25 chicks were found to be infected with coccidiosis viz. Eimeria tenella (15) Eimeria maxima (5) Eimeria necatrix (6) and Eimeria mitis (4). The anticoccidial efficacy of Azadirachta indica and Carica papaya with Salinomycin as a dietary feed supplement on the representative E. tenella (25 x 103 oocyst) infection challenged in broiler chicks was studied in six groups for the period of six weeks. A. indica and C. papaya leaves were administered in powder form at the concentration of 0.1% and 0.2% respectively. The Oocysts per gram (OPG) count were observed on 8th, 9th, 10th, 11th day of post inoculation (DPI). The challenged experimental chicks revealed haemorrhage, thickening of mucosa, cores of blood and ballooning of caecum. The experimental group T5 chicks treated with A. indica were analyzed to possess the maximum weight gain (2.003), better feed conversion ratio (FCR) (2.32), OPG count (5.87), livability percentage (88) and the lesion score (3.33). Chi-square test analysis revealed no significant differences among the treated groups and the performance parameters. Therefore, this study concludes that plant sources used as a remedial curate for coccidiosis is a perforated growth in the commercial broiler industries. PMID- 26142533 TI - Review: New diagnostic and therapeutic avenues for mesothelioma. AB - Mesothelioma is a rare form of cancer affecting the mesothelium lining. It is usually caused by asbestos exposure or exposure to nanofibers. Median survival is less than one year in the mesothelioma patients. Due to its severity, there is a dire necessity to find out new diagnostic and therapeutic strategies. Some recent strategies could help us in fighting against mesothelioma. Diagnostic tools include a range of biomarkers or biotechnological procedure. Therapeutic tools include chemotherapeutic strategies along with immunotherapy, gene therapy and alternative therapy. PMID- 26142534 TI - Review: Diverse pharmacological properties of Cinnamomum cassia: A review. AB - Cinnamomum cassia is widely utilized as a spice in different cookeries worldwide, especially in Asian cuisines. This herb is also being used in different forms of traditional medicine (Unani, Ayurvedic, Japanese and Chinese) for managing conditions like dyspepsia, peptic ulcer disease and ischemic brain injury. Recent studies have shown the scientific evidence for the medicinal use of this particular herb in several diseases like H. pylori infection, diabetes, brain ischemia and cancers. This article reviews the literature on potential benefits of the herb published within the last 10 years. The authors used Medical Subject Headings (MeSH) terms "Cinnamomum" with "cassia" or "arromaticum" to filter the PubMed database. To date, no systemic review focusing on medicinal use of C. cassia was found in the literature. Various research articles elucidating diverse pharmacological properties of C. cassia were identified. The standardised extract of C. cassia or the active compounds extracted from the herb might prove to be a novel candidate for early prevention and complimentary management of conditions like diabetes mellitus or H. pylori-associated disorders. PMID- 26142535 TI - Review: Apolipoprotein E (Apo E) gene polymorphism and coronary heart disease in Asian populations. AB - Apolipoprotein E (Apo E) is a basic component of very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL). It plays an important role in the clearance of cholesterol from circulation, and thereby slows down the process of atherosclerosis. Its 3 isoforms, E2, E3 and E4 are encoded by 3 alleles, e2, e3 and e4, respectively. E3 is the most common isoform in most populations in the world, while E2 is the least frequent isoform. A meta-analysis of several studies conducted on Asian populations revealed that carriers of e4 allele had 42% higher risk of coronary heart disease (CHD), while e2 allele had no significant association with this disease. Epidemiological studies performed in this region showed that E3 was the most prevalent isoform and most likely to be involved in CHD in Asia. Studies conducted in India indicated that individuals with e3/4 and e4/4 genotypes had considerably higher prevalence of dyslipidemia as compared to other genotypes, and hypertensive patients had high frequency of e4 allele. However, several other studies failed to show a relationship between ApoE gene polymorphism and CHD. Inadequate statistical power, low allele frequency, CHD phenotypes could be some of the possible reasons for conflicting results of some of these studies. This area of research is wide open and epidemiological studies with large sample size would be required to ascertain the relationships between ApoE gene polymorphism and CHD. PMID- 26142536 TI - Stressing out over long noncoding RNA. AB - Genomic studies have revealed that humans possess far fewer protein-encoding genes than originally predicted. These over-estimates were drawn from the inherent developmental and stimuli-responsive complexity found in humans and other mammals, when compared to lower eukaryotic organisms. This left a conceptual void in many cellular networks, as a new class of functional molecules was necessary for "fine-tuning" the basic proteomic machinery. Transcriptomics analyses have determined that the vast majority of the genetic material is transcribed as noncoding RNA, suggesting that these molecules could provide the functional diversity initially sought from proteins. Indeed, as discussed in this review, long noncoding RNAs (lncRNAs), the largest family of noncoding transcripts, have emerged as common regulators of many cellular stressors; including heat shock, metabolic deprivation and DNA damage. These stimuli, while divergent in nature, share some common stress-responsive pathways, notably inhibition of cell proliferation. This role intrinsically makes stress-responsive lncRNA regulators potential tumor suppressor or proto-oncogenic genes. As the list of functional RNA molecules continues to rapidly expand it is becoming increasingly clear that the significance and functionality of this family may someday rival that of proteins. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26142537 TI - First experience with single-source dual-energy computed tomography in six patients with acute arthralgia: a feasibility experiment using joint aspiration as a reference. AB - OBJECTIVES: Dual-energy computed tomography (DECT) is an emerging imaging technique for examining patients with suspected gout. Single-source dual-energy CT (S-DECT) is a new way of obtaining DECT information on conventional CT scanners rather than using special dual-source CT systems. METHODS: We tested the feasibility of S-DECT (320-row CT; Aquilion ONE, Toshiba Medical Systems, Otawara, Japan) in 6 patients (5 men, 1 woman; mean age 61.3, range 48 to 69 years) with acute arthralgia and suspected gout, and compared the S-DECT findings with the results of joint aspiration. RESULTS: Three patients had a diagnosis of gouty arthritis with negatively birefringent crystals in synovial fluid, in addition to gouty tophi in S-DECT. Three patients had no detectable crystals by polarization microscopy and no tophi on DECT. Their final diagnoses were rheumatoid arthritis, activated osteoarthritis, and septic arthritis in one case each. CONCLUSION: This initial experience suggests that S-DECT might be a valuable alternative to dual-source CT. Hence, more patients may benefit from its additional diagnostic abilities in the future. PMID- 26142538 TI - Soft-tissue aneurysmal bone cyst with translocation t(17;17)(p13;q21) corresponding to COL1A1 and USP6 loci. AB - We present the case of a 46-year-old woman with no significant past medical history who developed left mid-thigh pain and fullness. Imaging demonstrated a mineralized soft-tissue mass, which increased in size during a year of monitoring, but retained a circumscribed appearance. The mass was located in the medial soft tissues of the thigh, separate from the bone on imaging studies, and this finding was confirmed during excision. The mass showed gross and microscopic features of an aneurysmal bone cyst. This diagnosis was supported by cytogenetic analysis revealing a t(17;17)(p13;q21) translocation corresponding to the USP6 and COL1A1 loci. Soft-tissue aneurysmal bone cyst is a rare entity, with fewer than 25 reports in the literature. Limited cytogenetic information about these tumors is available. To our knowledge, the USP6 and COL1A1 rearrangement has only previously been described in a pediatric soft-tissue aneurysmal bone cyst. We also discuss the differential diagnosis of ossifying soft-tissue lesions. PMID- 26142540 TI - Comparison between conservative treatment and arthroscopic pull-out repair of the medial meniscus root tear and analysis of prognostic factors for the determination of repair indication. AB - INTRODUCTION: This study was undertaken to compare the clinical outcomes between the conservative treatment and pull-out repair of the medial meniscus root tear (MMRT), and to analyze the prognostic factors of the MMRT repair for the determination of repair indication. MATERIALS AND METHODS: 38 patients, diagnosed with a MMRT between August 2010 and February 2012, were retrospectively evaluated. Among these patients, 25 patients (pull-out repair group) underwent arthroscopic pull-out repair and the remaining 13 patients (conservative treatment group) underwent conservative management. Two groups were compared using the final clinical outcomes (using Tegner and Lysholm activity scale, IKDC subjective score). For the analysis of prognostic factors of the pull-out repair, patients' factors, radiologic, and magnetic resonance imaging factors were evaluated. Degrees of varus alignment (>=5 degrees ) and cartilage status (>=outerbridge III) were employed as a cut-off value in comparing the final clinical outcomes among the subgroups. RESULTS: In the final clinical results, the MMRT pull-out repair group had better IKDC subjective scores (p < 0.001), Tegner and Lysholm activity scale (p = 0.017). In the MMRT pull-out repair group, mild varus knee patient achieved better clinical outcome than the severe varus knee patient (p = 0.006). And the mild cartilage degenerative patient group achieved better outcomes than the severe cartilage degenerative patient group (p = 0.009). However, there was no significant difference between the severe varus alignment group and conservative treatment group (p = 0.487). Severe cartilage changes also show no significant difference (p = 0.643). CONCLUSIONS: The MMRT pull-out repair group had better clinical results than that the conservative treatment group. However, severe varus alignment and severe degeneration of cartilage status were a poor prognostic factor, and there was no significant difference between the severe varus alignment or severe cartilage change and the conservative treatment group in the clinical results. The other optional treatment could be recommended for patients who have MMRT with a severe varus knee alignment or severe cartilage. PMID- 26142539 TI - Does Measurement of Central Blood Pressure have Treatment Consequences in the Clinical Praxis? AB - Interest in relations between central aortic pressure and cardiovascular disease risk has increased markedly over the past two decades. Numerous studies have shown that higher pulse pressure is associated with increased risk. Further, pulse pressure differs variably and sometimes dramatically between the central aorta and the brachial artery, where blood pressure is generally measured. In light of the potential for variable misclassification of central systolic and pulse pressure by brachial measurements, central blood pressure has emerged as a potentially superior blood pressure measure. This brief review will examine the evidence supporting the use of central pressure to stratify risk and guide therapy in patients with hypertension. PMID- 26142541 TI - Current status of second-look arthroscopy after meniscal allograft transplantation: review of the literature. AB - INTRODUCTION: Clinical assessments do not accurately reflect the status of meniscal transplants and cannot evaluate the graft condition itself and joint preservation effects of meniscal allograft transplantation correctly. The purpose of this review was to assess the need and to ascertain the indication and the role of second-look arthroscopy for objective evaluation after MAT. MATERIALS AND METHODS: We performed a literature search to identify all published clinical studies on MAT with the following medical subject heading (MeSH) terms: "meniscus," "meniscal transplant," "transplantation and allograft," "meniscal and transplant." Include in the review are studies with at least 6 months clinical, radiological, and/or histological follow-up in human subjects. Evaluation method of MAT was reviewed with an aim to describe the frequency of second-look arthroscopy, its feasibility, patient compliance, purposes, and results. RESULTS: We identified 15 clinical studies that satisfied our inclusion and exclusion criteria. Only two studies always performed second-look arthroscopies. Most of the second-look arthroscopy was conducted mainly for the objective evaluation of meniscal allograft transplantation but, in several studies, arthroscopy was performed to treatment of other knee problem. CONCLUSIONS: Although second-look arthroscopy has inevitably ethical issues, especially for asymptomatic and well functioning knees, in this review, it could be a more dependable method available to detect meniscal healing if performed for certain indications such as a symptomatic patient with a magnetic resonance image indicating abnormalities. PMID- 26142542 TI - Early rehabilitation in the intensive care unit: an integrative literature review. AB - OBJECTIVES: The aim of this review is to appraise current research which examines the impact of early rehabilitation practices on functional outcomes and quality of life in adult intensive care unit (ICU) survivors. REVIEW METHOD USED: A systematic literature search was undertaken; retrieved data was evaluated against a recognised evaluation tool; research findings were analysed and categorised into themes; and a synthesis of conclusions from each theme was presented as an integrated summation of the topic. DATA SOURCES: Electronic databases of PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Ovid Medline and Google Scholar were searched using key search terms 'ICU acquired weakness', 'early rehabilitation' 'early mobility' and 'functional outcomes' combined with 'intensive care' and 'critical illness'. Additional literature was sourced from reference lists of relevant original publications. RESULTS: Five major themes related to the review objectives emerged from the analysis. These themes included: critically ill patients do not always receive physical therapy as a standard of care; ICU culture and resources determine early rehabilitation success; successful respiratory and physical rehabilitation interventions are tailored according to individual patient impairment; early exercise in the ICU prevents the neuromuscular complications of critical illness and improves functional status; early exercise in the ICU is effective, safe and feasible. CONCLUSIONS: A limited body of research supports early rehabilitation interventions to optimise the short term outcomes and long term quality of life for ICU survivors. Critical care nurses are in an excellent position to drive change within their departments ensuring that early rehabilitation practices are adopted and implemented. PMID- 26142543 TI - Mesenchymal stromal cells and rheumatic disorders. AB - Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. It could also indicate that MSC as currently employed are ineffective. Within the rheumatic diseases, SLE, rheumatoid arthritis (RA) and osteoarthritis (OA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive and no human studies have compared intra-articular MSC therapy to non-MSC techniques for osteoarthritis in the absence of surgery. Two randomised studies suggested benefit from the addition of bone marrow derived MSC and peripheral blood mononuclear cells added to surgical "standard of care" in knee OA and knee focal cartilage defects, respectively. The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed. PMID- 26142544 TI - Droplet Digital PCR for Absolute Quantification of EML4-ALK Gene Rearrangement in Lung Adenocarcinoma. AB - Crizotinib treatment significantly prolongs progression-free survival, increases response rates, and improves the quality of life in patients with ALK-positive non-small-cell lung cancer. Droplet Digital PCR (ddPCR), a recently developed technique with high sensitivity and specificity, was used in this study to evaluate the association between the abundance of ALK rearrangements and crizotinib effectiveness. FFPE tissues were obtained from 103 consecutive patients with lung adenocarcinoma. Fluorescent in situ hybridization (FISH) and ddPCR were performed. The results revealed that 14 (13.6%) of the 103 patients were positive by dual-color, break-apart FISH. Three variants (1, 2, and 3) of the EML4-ALK gene rearrangements were detected. Thirteen of 14 ALK-positive cases identified by FISH were confirmed by ddPCR (four with variant 1, two with variant 2, and seven with variant 3). The case missed by ddPCR was identified as KIF5B ALK gene rearrangement by PCR-based direct sequencing. Sixteen patients were detected with low copy numbers of EML4-ALK gene rearrangement, which failed to meet the positive cutoff point of FISH. Two of them responded well to crizotinib after unsuccessful chemotherapy. Our study indicates that ddPCR can be used as a molecular analytical tool to accurately measure the EML4-ALK rearrangement copy numbers in FFPE samples of lung adenocarcinoma patients. PMID- 26142545 TI - Synthesis of NAG-thiazoline-derived inhibitors for beta-N-acetyl-d hexosaminidases. AB - beta-N-Acetyl-d-hexosaminidases are responsible for the metabolism of glycoconjugates in diverse physiological processes that are important targets for medicine and pesticide development. Fourteen new NAG-thiazoline derivatives were synthesized by cyclization and click reaction using d-glucosamine hydrochloride as the starting material. All the compounds created were characterized by NMR and HRMS spectra. A preliminary bioassay, using four enzymes from two beta-N-acetyl-d hexosaminidase families, showed that most of the compounds synthesized exhibit selective inhibition of GH84 beta-N-acetyl-d-hexosaminidase. Among the compounds tested, compounds 5a (IC50=12.6 MUM, hOGA) and 5e (IC50=12.5 MUM, OfOGA) proved to be a highly selective and potent inhibitor. PMID- 26142546 TI - Predictions of dynamic changes in reaction rates as a consequence of incomplete mixing using pore scale reactive transport modeling on images of porous media. AB - We present a pore scale model capable of simulating fluid/fluid reactive transport on images of porous media from first principles. We use a streamline based particle tracking method for simulating flow and transport, while for reaction to occur, both reactants must be within a diffusive distance of each other during a time-step. We assign a probability of reaction (Pr), as a function of the reaction rate constant (kr) and the diffusion length. Firstly, we validate our model for reaction against analytical solutions for the bimolecular reaction (A+B->C) in a free fluid. Then, we simulate transport and reaction in a beadpack to validate the model through predicting the fluid/fluid reaction experimental results provided by Gramling et al. (2002). Our model accurately predicts the experimental data, as it takes into account the degree of incomplete mixing present at the sub-pore (image voxel) level, in contrast to advection-dispersion reaction equation (ADRE) model that over-predicts pore scale mixing. Finally, we show how our model can predict dynamic changes in the reaction rate accurately accounting for the local geometry, topology and flow field at the pore scale. We demonstrate the substantial difference between the predicted early-time reaction rate in comparison to the ADRE model. PMID- 26142547 TI - Integrating NZVI and carbon substrates in a non-pumping reactive wells array for the remediation of a nitrate contaminated aquifer. AB - The work explores the efficacy of a biochemical remediation of a nitrate contaminated aquifer by a combination of nanoscale zero-valent iron (NZVI) and bacteria supported by carbon substrates. Nitrate removal was first assessed in batch tests, and then in a laboratory bench-scale aquifer model (60cm length*40cm width*50cm height), in which a background flow was maintained. Water and natural sandy material of a stratified aquifer were used in the tests to enhance the reliability of the results. An array of non-pumping-reactive wells (NPRWs) filled with NZVI (d50=50nm, and SSA=22.5m(2)/g) mixed with carbon substrates (beech sawdust and maize cobs) was installed in the bench-scale aquifer model to intercept the flow and remove nitrate (NO3(-) conc.=105mg/l). The NPRW array was preferred to a continuous permeable reactive barrier (PRB) since wells can be drilled at greater depths compared to PRBs. The optimal well diameter, spacing among the NPRWs and number of wells in the bench-scale model were designed based on flow simulations using the semi-analytical particle tracking (advection) model, PMPATH. An optimal configuration of four wells, 35mm diameter, and capture width of 1.8 times the well diameter was obtained for a hydraulic conductivity contrast between reactive materials in the wells and aquifer media (KPM/Kaq=16.5). To avoid excessive proximity between wells, the system was designed so that the capture of the contaminated water was not complete, and several sequential arrays of wells were preferred. To simulate the performance of the array, the water that passed through the bench-scale NPRW system was re circulated to the aquifer inlet, and a nitrate degradation below the limit target concentration (10mg/l) was obtained after 13days (corresponding to 13 arrays of wells in the field). The results of this study demonstrated that using the NZVI mixed-carbon substrates in the NPRW system has a great potential for in-situ nitrate reduction in contaminated groundwater. This NPRW system can be considered a promising and viable technology in deep aquifers. PMID- 26142548 TI - An abnormally high expression of ISL-1 represents a potential prognostic factor in gastric cancer. AB - Insulin gene enhancer binding protein-1 (ISL-1) is a transcription factor involved in development of the heart, motor neurons, and pancreas. Our previous study indicated that ISL-1 was overexpressed in gastric cancer but not in other gastrointestinal tumors. However, no immunohistochemical or clinicopathological studies of ISL-1 in gastric carcinoma have been performed. The aim of this study was to determine the expression and prognostic value of ISL-1 in gastric carcinoma. A nude mouse xenograft model was established to study the role of ISL 1 on cancer genesis and development in vivo. Overexpression of ISL-1 significantly enhanced the tumorigenicity of NIH3T3 cells in vivo. ISL-1 expression was evaluated using immunohistochemistry in 456 human gastric carcinoma and normal tissues. ISL-1 was significantly overexpressed in gastric adenocarcinoma compared with normal gastric tissues. ISL-1 expression was significantly associated with depth of invasion, lymph node metastasis, TNM stage, and histological grade (P < .05, chi(2) test). Positive ISL-1 expression was associated with poorer 5-year overall survival in gastric cancer (P = .001, log-rank test). Multivariate Cox regression analysis demonstrated that ISL-1 expression (P = .047) could be an independent prognostic factor for overall survival in gastric carcinoma. This study suggests that ISL-1 may be a useful prognostic biomarker and may represent a novel therapeutic target for gastric adenocarcinoma. PMID- 26142549 TI - Spectrum of Imaging Findings in Paget's Disease of the Breast-A Pictorial Review. AB - PURPOSE: We aimed to demonstrate imaging features of Paget's disease of breast, which is an extremely uncommon malignancy that presents with changes in the nipple-areolar region that may or may not be associated with an underlying in situ component or invasive cancer. METHODS AND RESULTS: Mammography is the initial investigation of choice, having a high sensitivity especially in cases where a palpable mass is present. The addition of ultrasound improves the accuracy of mammography. When both mammography and ultrasound are negative, MRI may detect an underlying mass or ductal carcinoma in situ (DCIS). CONCLUSION: The surgical management of Paget's disease includes mastectomy with or without axillary dissection, though breast conservation surgery in the form of wide local excision can also be done in a selected group of patients. Management should be based on both clinical and imaging findings, including mammography and ultrasound, with MRI playing a crucial role in defining the extent of involvement. Teaching Points * To differentiate Paget's disease from other chronic skin conditions. * Mammographic and ultrasound findings of histopathologically established Paget's disease. * When ultrasound and mammogram are negative, MRI may detect underlying malignancy. PMID- 26142550 TI - The operative outcomes of displaced medial-end clavicle fractures. AB - BACKGROUND: Nonoperative treatment of displaced medial clavicle fractures often leads to poor functional outcomes and painful nonunions. This study investigates the functional outcomes of patients undergoing operative fixation of these fractures. METHODS: We investigated 27 patients undergoing operative fixation of a medial clavicle fracture; 24 had an acute, displaced fracture and 3 had fixation for nonunions. Preoperative radiographs or computed tomography scans were obtained, and data collected included age, sex, mechanism of injury, and fixation method. Follow-up included physical examination and radiographs for assessment of union; Disabilities of the Arm, Shoulder, and Hand scores at 12 months; and the recording of complications. RESULTS: The median age was 37 years (interquartile range, 17-47 years). There were 26 male patients and one female patient included, with 7 physeal injuries and 20 adult injuries. The most common mechanism of fracture was vehicular accident (n = 15). Three patients had operations for nonunions and 2 for a periprosthetic fracture medial to an existing plate. The fracture was fixed with plate and screws in 19 cases and with transosseous sutures in 8 cases. The median Disabilities of the Arm, Shoulder, and Hand score at 12 months was 0.4 (interquartile range, 0-5.0), with a union rate of 100% at 12 months. All patients had full shoulder range of motion at final follow-up and were able to return to preinjury occupational activities. There were no significant complications. CONCLUSION: Operative fixation of displaced medial clavicle fractures results in anatomic reconstruction and excellent functional outcomes, even in the setting of fixation performed for symptomatic nonunion. Early intervention can minimize the risk of painful nonunion. PMID- 26142552 TI - The pursestring technique for endoscopic revision of gastric bypass. PMID- 26142551 TI - Unsedated transnasal esophagoscopy for monitoring therapy in pediatric eosinophilic esophagitis. AB - BACKGROUND AND AIMS: Unsedated transnasal endoscopy (TNE) is safer and less costly than sedated EGD. The aim of this study was to evaluate the performance of TNE with biopsies in monitoring the esophageal mucosa of pediatric patients with eosinophilic esophagitis. METHODS: Patients between 8 and 17 years of age with eosinophilic esophagitis and their parents were enrolled. Unsedated TNE was performed. A 2.8-mm (1.2-mm channel) or a 4-mm flexible bronchoscope (2-mm channel) was used, and esophageal biopsy specimens were obtained. Biopsy specimen analysis, duration, adverse events, and billing charges of TNE were assessed. Immediately after TNE and a minimum of 2 weeks later, a modified Group Health Association of America 9 survey and a preference questionnaire were completed, respectively. RESULTS: Twenty-one of 22 enrolled patients underwent TNE. TNE was performed with no serious adverse events. Histopathological analysis revealed 0 eosinophils per high-power field (n = 12), fewer than 15 eosinophils per high power field (n = 4), and more than 15 eosinophils per high-power field (n = 5). The total epithelial surface area of mucosal biopsy samples from either TNE Forceps (1.2 mm or 2 mm biopsy channel forceps) compared with those obtained during the subject's previous EGD by using standard endoscopic forceps was not statistically different (P = .308 [1.2 mm]/P = .492 [2 mm]). All parents and 76.2% of subjects would undergo the TNE again. TNE was preferred over EGD by 85.7% of parents and 52.4% of subjects. The modified Group Health Association of America 9 survey revealed a high degree of satisfaction (average, 43.19 +/- 2.6; maximum score, 45). Charges associated with TNE were 60.1% lower than for previous EGDs. CONCLUSIONS: Unsedated TNE is an effective, lower-cost procedure for monitoring the esophageal mucosa of children with eosinophilic esophagitis. PMID- 26142553 TI - Reverse guidewire anchoring of the papilla for difficult cannulation due to a periampullary diverticulum. PMID- 26142554 TI - Prediction of patency capsule retention in known Crohn's disease patients by using magnetic resonance imaging. AB - BACKGROUND AND AIMS: Evaluation of small-bowel patency is recommended before swallowing video capsule endoscopy to prevent capsule retention. This study aimed to evaluate the ability of magnetic resonance enterography (MRE) to predict patency capsule (PC) retention in patients with Crohn's disease and to identify the most predictive imaging features for retention. METHODS: Fifty-seven patients prospectively underwent MRE and PC. Two radiologists predicted PC retention. Interrater reliability was determined by using Cohen's kappa coefficient. The sensitivity, specificity, and positive and negative predictive values were calculated for the predictions. Evaluation of the imaging features was done using the t test and receiver-operating characteristics; t-tests were also performed on the clinical parameters. RESULTS: The kappa value for interrater reliability was 0.58. The sensitivity, specificity, PPV, and NPV for the predictions by the 2 radiologists were 92.3%, 59%, 40%, 96.3%, and 100%, 52.3%, 38.2%, 100%, respectively. The maximal stricture length (9.7 +/- 3.66 cm vs 7.0 +/- 3.08 cm, P = .04) and the number of prestenotic dilations (1.9 +/- 1.07 vs 1.0 +/- 1.38, P = .03) were associated with PC retention. The area under the receiver-operating characteristic curves was 0.69 for the maximal stricture length and 0.751 for the number of prestenotic dilations. The phenotype of the disease was the only clinical parameter significantly correlated with PC retention. CONCLUSIONS: MRE has a high NPV and sensitivity for PC retention. When capsule retention is suggested by MRE, PC should be performed before the video capsule endoscopy examination. The maximal stricture length and the number of prestenotic dilations were found to be the most predictive imaging features for PC retention. PMID- 26142555 TI - Efficacy of carbon dioxide insufflation during gastric endoscopic submucosal dissection: a randomized, double-blind, controlled, prospective study. AB - BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is commonly performed under air insufflation and is often accompanied by abdominal discomfort. CO2 is absorbed more rapidly by the body than is air; however, the use of CO2 insufflation in ESD remains controversial. This randomized, double-blind, controlled, prospective study was designed to assess the efficacy of CO2 versus air insufflation in gastric ESD. METHODS: Between May 2012 and August 2014, a total of 110 patients with gastric tumors were randomly assigned to the CO2 insufflation (CO2 group, n = 54) or air insufflation group (air group, n = 56). Abdominal pain after ESD was chronologically recorded via visual analog scale (VAS) scores. Secondary outcome measurements were adverse events, abdominal circumference, amount of sedatives prescribed, and use of analgesics. RESULTS: Neither the baseline patient characteristics nor the mean procedural time differed between the groups. The VAS score for abdominal pain was 35.2 in the CO2 insufflation group versus 48.5 in the air insufflation group 1 hour after ESD (P = .026), 27.8 versus 42.5 three hours after ESD (P = .007), 18.4 versus 34.8 six hours after ESD (P = .001), and 9.2 versus 21.9 one day after ESD (P < .001). Changes in abdominal circumference, the amounts of sedative drugs taken, and the adverse events did not differ between the groups. However, the air insufflation group required more analgesics than did the CO2 insufflation group (CO2 group, 22.0% [11/50]; air group, 42.3% [22/52]; P = .028). CONCLUSIONS: CO2 insufflation during gastric ESD significantly reduced abdominal pain and analgesic usage compared with air insufflation. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01579071.) PMID- 26142556 TI - The esophageal biopsy "pull" sign: a highly specific and treatment-responsive endoscopic finding in eosinophilic esophagitis (with video). AB - BACKGROUND AND AIMS: Esophageal biopsy specimens from patients with eosinophilic esophagitis (EoE) can feel firm, with resistance felt when pulling the forceps to obtain the tissue sample. We aimed to assess the diagnostic utility of the esophageal biopsy "pull" sign and determine its histologic associations and response to treatment. METHODS: This was a prospective cohort study of adults undergoing outpatient upper endoscopy. Cases of EoE were diagnosed per consensus guidelines, and patients were subsequently treated with either topical steroids or dietary elimination. Control subjects were individuals who did not have EoE. The frequency of the esophageal biopsy "pull" sign was assessed in EoE patients and controls, and diagnostic metrics were calculated. The "pull" sign was also reassessed in patients after therapy. RESULTS: A total of 83 EoE patients and 121 control subjects were included. Sixty-three EoE patients (76%) were "pull" sign positive compared with just 2 control subjects (2%; P < .001), corresponding to a sensitivity and specificity of 76% and 98%, positive and negative predictive values of 97% and 86%, and positive and negative likelihood ratios of 45.9 and 0.245, respectively. The "pull" sign was the strongest endoscopic predictor of EoE case status at baseline and was less frequent after successful treatment (20% vs 79%; P < .001). CONCLUSIONS: The "pull" sign is highly specific for EoE and is rarely seen in non-EoE control subjects. In patients with EoE who respond to treatment, the "pull" sign often resolves. The "pull" sign may be a simple and easily obtained measure of esophageal remodeling. PMID- 26142557 TI - Endoscopic photography and image documentation. PMID- 26142558 TI - EUS-guided gallbladder drainage with a lumen-apposing metal stent (with video). AB - BACKGROUND AND AIMS: Nonsurgical techniques for gallbladder drainage are percutaneous, and endoscopic. EUS-guided transmural gallbladder drainage (EUS GBD) is a relatively new approach, although data are limited. Our aim was to describe the outcome after EUS-GBD with a lumen-apposing metal stent (LAMS). PATIENTS AND METHODS: This was a retrospective review of prospectively collected data on 15 nonsurgical patients who underwent EUS-GBD for various indications. Procedures were performed at 3 tertiary care centers with expertise in the management of complex biliary problems. The main outcome measures were technical and clinical success and adverse events. RESULTS: Fifteen patients (8 male, 7 female) with a median age of 74 years (range 42-89) underwent EUS-GBD by using a LAMS to decompress the gallbladder (7 patients calculous cholecystitis, 4 acalculous cholecystitis, 2 patients biliary obstruction, 1 patient gallbladder hydrops, 1 patient symptomatic cholelithiasis). Patients were nonsurgical candidates according to the American Society of Anesthesiologists Physical Status Classification System; findings were class IV or higher in 9 patients and advanced malignancies in 6. Percutaneous transhepatic gallbladder drainage (PT GBD) was refused by all patients and was further precluded by perihepatic ascites in 3 patients, coagulopathy or need for anticoagulation in 4 patients, and need for internal biliary drainage in 2 patients. Transduodenal access and stenting was achieved in 14 of 15 patients and transgastric stenting was achieved in 1. Technical success was achieved in 14 of 15 patients (93%), whereas clinical success was achieved in all 15 patients with a median follow-up of 160 days. One mild adverse event (postprocedure fever for 3 days) was noted. The limitations of this study are the small select group of patients and retrospective study design. CONCLUSIONS: EUS-GBD with a LAMS is technically safe and effective for decompressing the gallbladder for cholecystitis and biliary or cystic duct obstruction in patients who are poor surgical candidates. PMID- 26142559 TI - Discovery of characteristic chemical markers for classification of aconite herbs by chromatographic profile and probabilistic neural network. AB - Most Aconitum species, also known as aconite, are extremely poisonous, so it must be identified carefully. Differentiation of Aconitum species is challenging because of their similar appearance and chemical components. In this study, a universal strategy to discover chemical markers was developed for effective authentication of three commonly used aconite roots. The major procedures include: (1) chemical profiling and structural assignment of herbs by liquid chromatography with mass spectrometry (LC-MS), (2) quantification of major components by LC-MS, (3) probabilistic neural network (PNN) model to calculate contributions of components toward species classification, (4) discovery of minimized number of chemical markers for quality control. The MS fragmentation pathways of diester-, monoester-, and alkyloyamine-diterpenoid alkaloids were compared. Using these rules, 42 aconite alkaloids were identified in aconite roots. Subsequently, 11 characteristic compounds were quantified. A component species modeling by PNN was then established combining the 11 analytes and 26 batch samples from three aconite species. The contribution of each analyte to species classification was calculated. Selection of fuziline, benzoylhypaconine, and talatizamine, or a combination of more compounds based on a contribution order, can be used for successful categorization of the three aconite species. Collectively, the proposed strategy is beneficial to selection of rational chemical markers for the species classification and quality control of herbal medicines. PMID- 26142560 TI - Flow-through cross-polarized imaging as a new tool to overcome the analytical sensitivity challenges of a low-dose crystalline compound in a lipid matrix. AB - Assessing the physical state of a low-dose active compound in a solid lipid or polymer matrix is analytically challenging, especially if the matrix exhibits some crystallinity. The aim of this study was first to compare the ability of current methods to detect the presence of a crystalline model compound in lipid matrices. Subsequently, a new technique was introduced and evaluated because of sensitivity issues that were encountered with current methods. The new technique is a flow-through version of cross-polarized imaging in transmission mode. The tested lipid-based solid dispersions (SDs) consisted of beta-carotene (BC) as a model compound, and of Gelucire 50/13 or Geleol mono- and diglycerides as lipid matrices. The solid dispersions were analyzed by (hyper) differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and microscopic techniques including atomic force microscopy (AFM). DSC and XRPD could analyze crystalline BC at concentrations as low as 3% (w/w) in the formulations. However, with microscopic techniques crystalline particles were detected at significantly lower concentrations of even 0.5% (w/w) BC. A flow-through cross-polarized imaging technique was introduced that combines the advantage of analyzing a larger sample size with high sensitivity of microscopy. Crystals were detected easily in samples containing even less than 0.2% (w/w) BC. Moreover, the new tool enabled approximation of the kinetic BC solubility in the crystalline lipid matrices. As a conclusion, the flow-through cross-polarized imaging technique has the potential to become an indispensable tool for characterizing low-dose crystalline compounds in a lipid or polymer matrix of solid dispersions. PMID- 26142561 TI - Application of capillary electrophoresis-frontal analysis for comparative evaluation of the binding interaction of captopril with human serum albumin in the absence and presence of hydrochlorothiazide. AB - The application of capillary electrophoresis-frontal analysis for comparative evaluation of the binding interaction between antihypertensive drug captopril and human serum albumin in the absence and presence of diuretic drug hydrochlorothiazide was presented in this work. At near-physiological conditions (67mM phosphate buffer, pH 7.4, I=0.17, 37 degrees C), the individual solution of 100MUM captopril and the co-binding solution with 60MUM hydrochlorothiazide added were pre-equilibrated with series concentrations of HSA (10-475MUM) respectively, introducing hydrodynamically into an uncoated fused silica capillary (35cm*50MUm I.D. with 26.5cm effective length). The values of number of binding sites, the binding constant for captopril and hydrochlorothiazide binding to HSA were obtained, respectively. It can be found that both drugs exhibit moderate binding properties towards HSA and there does not exist significant competitive binding effects between them. PMID- 26142562 TI - Morphological characterisation of vesicular structures in the canine ejaculate. AB - Membrane vesicles (MV) have been identified in seminal plasma from various species and they are thought to have a significant impact on semen quality and fertilisation. Although recently presence of MV has been also described in the canine ejaculate, detailed knowledge on their morphology is missing by now. This is, however, needed to provide a basis for detailed biochemical and functional studies as it is generally assumed that different MV populations are responsible for distinct tasks. MV were prepared for light (LM) and transmission electron microscopy (TEM) analysis using samples from normospermic dogs (n=15), hypokinozoospermic dogs (n=2, h) and one castrated azoospermic dog (a). For TEM, a new preparation protocol was used resulting in a higher MV retrieval rate. Using fractionated semen samples, most MV were identified in the second (sperm rich) fraction in LM. Using pooled ejaculates, three different MV types could be identified in LM: (1) large MV with a marginal accumulation of opaque, granulated material, (2) medium- to small size MV with dense, opaque content and (3) small MV with no further defined contents. No direct contact between sperm and MV could be visualised. In TEM, 11 different MV types were identified based on diameter, structure, contents and electron density of contents as well as presence, number and size of smaller MV inside the MV itself. In normospermic males, secondary vesicles (type i, H, K1/2) included smaller vesicles and had a weighted mean diameter of 409.46 nm; hereof types i, H and K1 were smaller (mean: 287.55 nm, range: 51.25-994.86 nm) and type K2 was larger (mean: 1746.43 nm, range: 1003.66 3289.34 nm). Primary vesicles (mean diameter: 135.29 nm) - without vesicles inside - were differentiated into larger MV (A, B, C1/2) with a mean diameter of 219.63 nm (range: 39.08-1300.13 nm) and small primary MV (F, G) with a mean diameter of 66.12 nm (range: 24.62-99.84 nm). Whereas all mentioned MV were round to oval and mostly double-, rarely multiple-membrane surrounded, one longish primary MV type (L) was identified. In general, small primary vesicles were most common independent of semen quality, but distribution frequency of vesicle types differed between normospermic, pathospermic dogs and the castrated male. Mean weighted diameter of MV was 195.14 nm (range: 24.62-3289.34 nm) in normospermic males with the maximum diameter being smaller in the other dogs (h: 2096.78 nm; a: 1314.06 nm). Our results provide new information about ultrastructure and distribution frequency of canine MV in normospermic males and point to possible differences in MVs depending on semen quality. They provide the basis for further detailed functional analysis of MV subpopulations. Furthermore, the presence of MV in the castrated azoospermic male confirms an at least partly prostatic origin of canine MV. PMID- 26142563 TI - Lack of effect of nucleus accumbens dopamine D1 receptor blockade on consumption during the first two days of operant self-administration of sweetened ethanol in adult Long-Evans rats. AB - The mechanisms underlying ethanol self-administration are not fully understood; however, it is clear that ethanol self-administration stimulates nucleus accumbens dopamine release in well-trained animals. During operant sweetened ethanol self-administration behavior, an adaptation in the nucleus accumbens dopamine system occurs between the first and second exposure, paralleling a dramatic increase in sweetened ethanol intake, which suggests a single exposure to sweetened ethanol may be sufficient to learn the association between sweetened ethanol cues and its reinforcing properties. In the present experiment, we test the effects of blockade of nucleus accumbens dopamine D1 receptors on operant sweetened ethanol self-administration behavior during the first 2 days of exposure. Adult male Long-Evans rats were first trained to self-administer 10% sucrose (10S) across 6 days in an appetitive and consummatory operant model (appetitive interval: 10-min pre-drinking wait period and a lever response requirement of 4; consummatory interval: 20-min access to the drinking solution). After training on 10S, the drinking solution was switched to 10% sucrose plus 10% ethanol (10S10E); control rats continued drinking 10S throughout the experiment. Bilateral nucleus accumbens microinjections of the dopamine D1 antagonist, SCH 23390 (0, 1.0, or 3.0 MUg/side), immediately preceded the first two sessions of drinking 10S10E. Results show that blocking nucleus accumbens dopamine D1 receptors has little or no influence on consumption during the first 2 days of exposure to the sweetened ethanol solution or maintenance of sucrose-only drinking. Furthermore, the high dose of SCH-23390, 3.0 MUg/side, reduced open field locomotor activity. In conclusion, we found no evidence to suggest that nucleus accumbens D1 receptor activation is involved in consumption of a sweetened ethanol solution during the first 2 days of exposure or maintenance of sucrose drinking, but rather D1 receptors seem necessary for general locomotor activity that contributes to initiation of appetitive behavior. PMID- 26142565 TI - Oral Congenital Melanocytic Nevus: A Rare Case Report and Review of the Literature. AB - Melanocytic nevi are congenital or acquired benign proliferations of cells of melanocytic origin. Oral congenital melanocytic nevi are rare, and only a few cases have been reported in the literature. The purpose of this study is to present the clinical, histological and immunohistochemical features of an oral congenital melanocytic nevus in a 16-year-old female with an 11-year follow-up and to review the pertinent literature. The reported case is the fifth well documented case report of oral congenital melanocytic nevus in the English literature and the first with a long period of follow-up, thereby making it an important contribution to the knowledge regarding this uncommon oral mucosa lesion. PMID- 26142564 TI - Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats. AB - Sensitivity to the interoceptive effects of alcohol is blunted following a period of exposure to the stress hormone corticosterone (CORT), an effect that is suggested to be related, in part, to glutamatergic neuroadaptations. Group II metabotropic glutamate receptors (subtypes 2 and 3; mGluR2/3) modulate several drug- and alcohol-related behaviors, including the interoceptive (discriminative stimulus) effects of alcohol. Therefore, we sought to determine if manipulation of mGluR2/3 would restore sensitivity to the interoceptive effects of alcohol following CORT exposure. Using a two-lever drug discrimination task, male Long Evans rats were trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water. First, the effect of mGluR2/3 antagonism on the discriminative stimulus effects of alcohol was determined using LY341495 (0.3-3.0 mg/kg; intraperitoneal [IP]). Next, the effects of mGluR2/3 antagonism and activation were assessed in discrimination-trained animals exposed to CORT (300 MUg/mL) in the home cage drinking water or water only, for 7 days. Following CORT exposure, decreased sensitivity to alcohol (1 g/kg) was observed. Pretreatment with the mGluR2/3 agonist LY379268 (1.0-3.0 mg/kg; IP), but not the mGluR2/3 antagonist (0.3-1.0 mg/kg; IP), restored sensitivity to alcohol. Additionally, in water controls, mGluR2/3 antagonism and mGluR2/3 activation disrupted expression of the discriminative stimulus effects of alcohol. Together, these findings suggest that blunted sensitivity to the interoceptive effects of alcohol following an episode of heightened stress hormone levels may be due to adaptations in mGluR2/3-related systems. The ability of mGluR2/3 activation to restore sensitivity to alcohol under these conditions lends further support for the importance of these receptors under stress-related conditions. PMID- 26142566 TI - Music listening as a means of stress reduction in daily life. AB - The relation between music listening and stress is inconsistently reported across studies, with the major part of studies being set in experimental settings. Furthermore, the psychobiological mechanisms for a potential stress-reducing effect remain unclear. We examined the potential stress-reducing effect of music listening in everyday life using both subjective and objective indicators of stress. Fifty-five healthy university students were examined in an ambulatory assessment study, both during a regular term week (five days) and during an examination week (five days). Participants rated their current music-listening behavior and perceived stress levels four times per day, and a sub-sample (n = 25) additionally provided saliva samples for the later analysis of cortisol and alpha-amylase on two consecutive days during both weeks. Results revealed that mere music listening was effective in reducing subjective stress levels (p = 0.010). The most profound effects were found when 'relaxation' was stated as the reason for music listening, with subsequent decreases in subjective stress levels (p <= 0.001) and lower cortisol concentrations (p <= 0.001). Alpha-amylase varied as a function of the arousal of the selected music, with energizing music increasing and relaxing music decreasing alpha-amylase activity (p = 0.025). These findings suggest that music listening can be considered a means of stress reduction in daily life, especially if it is listened to for the reason of relaxation. Furthermore, these results shed light on the physiological mechanisms underlying the stress-reducing effect of music, with music listening differentially affecting the physiological stress systems. PMID- 26142567 TI - Trait anger but not anxiety predicts incident type 2 diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA). AB - OBJECTIVE: Prior studies have shown a bidirectional association between depression and type 2 diabetes mellitus (T2DM); however, the prospective associations of anger and anxiety with T2DM have not been established. We hypothesized that trait anger and anxiety would predict incident T2DM, independently of depressive symptoms. RESEARCH DESIGN AND METHODS: In the Multi ethnic Study of Atherosclerosis (MESA), we prospectively examined the association of trait anger and trait anxiety (assessed via the Spielberger Trait Anger and Anxiety Scales, respectively) with incident T2DM over 11.4 years in 5598 White, Black, Hispanic, and Chinese participants (53.2% women, mean age 61.6 years) at baseline without prevalent T2DM or cardiovascular disease. We used Cox proportional hazards models to calculate the hazard ratios (HR) of incident T2DM by previously defined anger category (low, moderate, high), and anxiety quartile, as there were no previously defined categories. RESULTS: High total trait anger was associated with incident T2DM (HR 1.50; 95% CI 1.08-2.07) relative to low total trait anger. The association was attenuated following adjustment for waist circumference (HR 1.32; 95% CI 0.94-1.86). Higher anger reaction was also associated with incident T2DM (HR=1.07; 95% CI 1.03-1.11) that remained significant after adjusting for potential confounders/explanatory factors. In contrast, trait anxiety did not predict incident T2DM. CONCLUSIONS: High total trait anger and anger reaction are potential modifiable risk factors for T2DM. Further research is needed to explore the mechanisms of the anger-diabetes relationship and to develop preventive interventions. PMID- 26142569 TI - The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways. AB - Thioredoxin (Trx), a 12 kDa protein, has different functions in different cellular environments, playing important anti-oxidative and anti-apoptotic roles and regulating the expression of transcription factors. Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts from glucose protein condensation reactions and are considered crucial to the development of diabetic nephropathy, retinopathy, neurodegeneration and atherosclerosis. The aim of this study was to use a Trx inhibitor to investigate the effects and mechanism of Trx down-regulation on AGE-induced Neuro2a cell apoptosis. Neuro2a cells were cultured in vitro and treated with different conditions. The apoptosis and proliferation of Neuro2a cells were detected using flow cytometry, DNA-Ladder and CCK8 assays. Rho 123 was used to detect the mitochondrial membrane potential. ROS generation and caspase3 activity were detected using a DCFH-DA probe and micro plate reader. Western blotting and real-time PCR were used to detect the expression of proteins and genes. We found that the down-regulation of thioredoxin could accelerate AGE-induced apoptosis in Neuro2a cells. A possible underlying mechanism is that the down-regulation of thioredoxin stimulated the up regulation of ASK1, p-JNK, PTEN, and Txnip, as well as the down-regulation of p AKT, ultimately increasing ROS levels and caspase3 activity. PMID- 26142570 TI - Anticonvulsant properties of Euterpe oleracea in mice. AB - Acai (Euterpe oleracea Mart.), a highly consumed fruit in Amazon, is from a common palm with remarkable antioxidant properties. Because oxidative stress and seizures are intimately linked, this study investigated the potential neuroprotective and anticonvulsant effects of commercial clarified acai juice (EO). EO did not alter spontaneous locomotor activity. Four doses of EO were sufficient to increase latencies to both first myoclonic jerk and first generalized tonic-clonic seizure and significantly decrease the total duration of tonic-clonic seizures caused by pentylenetetrazol administration. Also, electrocortical alterations provoked by pentylenetetrazol were prevented, significantly decreasing amplitude of discharges and frequencies above 50 Hz. EO was also able to completely prevent lipid peroxidation in the cerebral cortex, showing a potent direct scavenging property. These results demonstrate for the first time that E. oleracea significantly protects against seizures and seizure related oxidative stress, indicating an additional protection for humans who consume this fruit. PMID- 26142571 TI - [New therapeutic approaches in type 2 diabetes mellitus]. PMID- 26142568 TI - Cumulative stress pathophysiology in schizophrenia as indexed by allostatic load. AB - BACKGROUND: The etiopathophysiology of schizophrenia has long been linked to stress and the influence of stress is important in all stages of the illness. Previous examinations of perceived stress and acute stress responses may not capture this longitudinal stress pathophysiology. We hypothesized that the cumulative negative effects of stress, indexed by allostatic load (AL), would be elevated in schizophrenia, and that the AL paradigm would be relevant to our understanding of pathophysiology in schizophrenia. METHODS: We assessed allostatic load in 30 patients with schizophrenia (SZ; mean age = 33; 17 males) and 20 healthy controls (HC; mean age = 35; 12 males) using 13 cardiovascular, metabolic, neuroendocrine and immune biomarkers. Participants' perceived stress over the past month, functional capacity and psychiatric symptoms were also measured. RESULTS: Controlling for age, SZ had significantly higher AL as compared to HC (p = 0.007). Greater AL was present in both early course and chronic SZ, and was associated with reduced functional capacity (p = 0.006) and more psychotic symptoms (p = 0.048) in SZ. Current level of perceived stress was not significantly elevated in SZ or associated with AL in either group. CONCLUSIONS: The higher AL found in SZ may reflect increased bodily "wear and tear", possibly caused by more chronic stress exposure or maladaptive responses to stress over time, although additional research is required to differentiate these causes. The higher AL is similarly present in early and chronic SZ, suggesting primary maladaptive stress physiology rather than secondary effects from medications or chronic illness. PMID- 26142572 TI - A short, high-temperature treatment of host larvae to analyze Wolbachia-host interactions in the moth Ostrinia scapulalis. AB - Maternally inherited endosymbiotic bacteria of the genus Wolbachia cause various reproductive alterations in their hosts. Wolbachia induces male-specific death during embryonic and larval stages in the moth Ostrinia scapulalis. To investigate how the density of Wolbachia affects their performance in the host, we attempted to reduce its density using a short, high-temperature treatment of the host at the larval stage. Individuals cured of infection as well as sexual mosaics, which harbor Wolbachia, were obtained by this method in the next generation. The sex of uninfected offspring was exclusively male, similar to that of the offspring of larvae treated with antibiotics. A strong correlation was found between Wolbachia density in female moths and the sex ratio of their progeny. These results suggest that a short, high-temperature treatment at the larval stage reduced the density of Wolbachia in the adult stage, and, hence, inhibited interference with the host's development in the next generation. Since the direct effects of the heat treatment on Wolbachia were transient, this method may be useful for specifying the critical time for interference by Wolbachia in host development. PMID- 26142573 TI - Bare fingers, but no obvious influence of "prickly" Velcro! In the absence of parents' encouragement, it is not clear that "sticky mittens" provide an advantage to the process of learning to reach. AB - In their critique of our mittens study, Needham et al. (2015. Infant Behavior and Development) describe our findings as "surprising." Further; they suggest that babies in our "sticky mittens" condition may have been discouraged from reaching because, in our study, infants may have touched "prickly" Velcro with their bare fingers. In this response, we present data analyses that do not support the interpretation that finger contact with our Velcroed toy surfaces was associated with poor reaching performance in our "sticky" mittens group. We also clarify that our toys were mainly covered with "non-prickly" Velcro. To explain discrepancies between studies, we restate the original intent of our study and reasons for our methodological modifications. We point to confounds and lack of critical control conditions in the Needham et al. studies, which prevent the making of firm inferences about the effectiveness of the "sticky mittens experience" on the learning to reach process. We also present additional analyses on our "sticky" mittens group showing that the increasing rate of finger touch on the toy leads to greater reaching performance while the rate of toy sticking to the mittens does not. We discuss the importance of sensory-motor experience on the development of learning to reach in infancy and conclude that our results are not surprising. PMID- 26142574 TI - Associate Editor for Endourology and Stones: Dr. Brian R. Matlaga. PMID- 26142575 TI - Can Sexual Intercourse Be an Alternative Therapy for Distal Ureteral Stones? A Prospective, Randomized, Controlled Study. AB - OBJECTIVE: To investigate the effect of sexual intercourse on spontaneous passage of distal ureteral stones. MATERIAL AND METHODS: The patients were randomly divided into 3 groups with random number table envelope method. Patients in group 1 were asked to have sexual intercourse at least 3-4 times a week. Patients in group 2 were administered tamsulosin 0.4 mg/d. Patients in group 3 received standard medical therapy alone and acted as the controls. The expulsion rate was controlled after 2 and 4 weeks. Differences in the expulsion rate between groups were compared with the chi-square test for 3 * 2 tables. P <.05 was considered as statistically significant. RESULTS: The mean stone size was 4.7 +/- 0.8 mm in group 1, 5 +/- 1 mm group 2, and 4.9 +/- 0.8 mm group 3 (P = .4). Two weeks later, 26 of 31 patients (83.9%) in the sexual intercourse group, and 10 of 21 patients (47.6%) in tamsulosin group passed their stones, whereas 8 of 23 patients (34.8%) in the control group passed their stones (P = .001). The mean stone expulsion time was 10 +/- 5.8 days in group 1, 16.6 +/- 8.5 days in group 2, and 18 +/- 5.5 days in group 3 (P = .0001). CONCLUSION: Our results have indicated that patients who have distal ureteral stones <=6 mm and a sexual partner may be advised to have sexual intercourse 3-4 times a week to increase the probability of spontaneous passage of the stones. PMID- 26142576 TI - Editorial Comment. PMID- 26142577 TI - Predictive Value of Leukocytosis for Infectious Complications After Percutaneous Nephrolithotomy. AB - OBJECTIVE: To investigate the natural history of white blood cell (WBC) values and incidence of leukocytosis after percutaneous nephrolithotomy (PCNL), factors associated with development of postoperative leukocytosis, and predictive value of WBC count for infection. METHODS: A total of 303 patients who underwent PCNL for renal stones were included in the recent study. Electronic medical records of the patients were reviewed retrospectively to collect daily serum leukocyte counts and perioperative cultures. WBC count was followed daily for patients with positive urine culture and/or postoperative fever until leukocyte levels turned to normal limits. RESULTS: Leukocytosis was detected in 133 of the 303 patients (43.9%). The mean preoperative and postoperative WBC counts were 7.73 +/- 2.01 * 10(6) cells/MUL and 11.9 +/- 3.31 * 10(6) cells/MUL, respectively. The average postoperative WBC count increased by 4.2 +/- 2.99 * 10(6) cells/MUL over the first 2 postoperative days. Receiver operating characteristic curve analysis resulted in an area under the curve of 0.87 and 0.80 for postoperative WBC count and absolute WBC count difference, respectively. The thresholds provided by the analysis were 14.05 * 10(6) cells/MUL and an increase greater than 5.25 * 10(6) cells/MUL, respectively. CONCLUSION: Our data show postoperative leukocytosis is common after PCNL and represents a normal physiologic response to surgery. Our study demonstrated that 14.05 * 10(3) * 10(6) cells/MUL WBC count and absolute difference in WBC count from baseline of 5.25 * 10(3) * 10(6) cells/MUL were significantly associated with post-PCNL sepsis development. Further studies are needed to determine the significance of leukocytosis for infectious complications after PCNL. PMID- 26142578 TI - Impact of a Genomic Classifier of Metastatic Risk on Postprostatectomy Treatment Recommendations by Radiation Oncologists and Urologists. AB - OBJECTIVE: To evaluate how a genomic classifier (GC) that predicts the risk of metastasis after prostatectomy would impact adjuvant treatment recommendations made by radiation oncologists and urologists. The 2 specialties often disagree about postprostatectomy adjuvant treatment recommendations. MATERIALS AND METHODS: Twenty-six radiation oncologists and 20 urologists with genitourinary oncology expertise reviewed de-identified clinical results from 11 patients after radical prostatectomy and made adjuvant treatment recommendations. The same cases were later randomized and reassigned, and treatment recommendations were made using the clinical information and GC test results together. RESULTS: Using clinical information alone, observation was recommended in 42% of decisions made by urologists vs 23% by radiation oncologists (P < .0001). The GC test results altered 35% and 45% of treatment recommendations made by radiation oncologists and urologists, respectively. Multivariate analysis showed GC risk was the strongest factor influencing treatment recommendations by both specialties, with an adjusted odds ratio of 4.17 (95% confidence interval [CI], 2.26-7.70) and 6.51 (95% CI, 4.29-9.88) for radiation oncologists and urologists, respectively. GC results indicating high metastatic risk resulted in intensification of treatment, whereas low metastatic risk resulted in less aggressive recommendations. The GC results increased interdisciplinary agreement in treatment recommendations, as the odds of a recommendation for adjuvant treatment by urologists vs radiation oncologists increased from 0.27 (95% CI, 0.17-0.44) to 0.46 (95% CI, 0.29-0.75) after results of the GC test were available. CONCLUSION: The GC test significantly influenced adjuvant postprostatectomy treatment recommendations, reduced disagreement between radiation oncologists and urologists, and has the potential to enhance personalization of postprostatectomy care. PMID- 26142579 TI - Sperm Parameters and Semen Levels of Inflammatory Cytokines in Helicobacter pylori-infected Men. AB - OBJECTIVE: To explore the relationships between seminal interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) with semen parameters, sperm apoptosis, and necrosis in subjects infected by Helicobacter pylori (HP) expressing and not expressing CagA. METHODS: In 109 selected patients, HP infection and seminal levels of IL-6 and TNF-alpha were determined using enzyme-linked immunosorbent assays. Western blotting was used to detect antibodies to CagA. Semen parameters were determined following World Health Organization guidelines and sperm apoptosis and necrosis by annexin V and propidium iodide assay. RESULTS: Twenty eight subjects were infected by HP (HP+); among them, 12 were CagA seropositive (CagA+) and 16 were negative (CagA-). Eighty-one men were HP seronegative (HP-). Semen TNF-alpha and IL-6 concentrations were increased in HP+ vs HP- groups (TNF alpha: 41 pg/mL vs 27 pg/mL; IL-6: 11 pg/mL vs 5 pg/mL; P <.01). In comparison to the HP- group, CagA+ group showed reduced sperm motility (24% vs 32% motile sperm; P <.05), enhanced necrosis (33.5% vs 21% necrotic sperm; P <.05), and increased cytokines levels (TNF-alpha: 46 pg/mL vs 27 pg/mL; P <.01; IL-6: 17.5 pg/mL vs 5 pg/mL; P <.01). Sperm motility of CagA+ group was lower vs CagA- group (24% vs 36.5% motile sperm; P <.05). Both IL-6 and TNF-alpha levels positively correlated with the percentage of necrotic sperm (P <.001). CONCLUSION: CagA+ HP infection increases semen levels of inflammatory cytokines, which may reduce sperm motility and determine sperm damage and contribute to reduce the reproductive potential in men. PMID- 26142580 TI - Editorial Comment. PMID- 26142581 TI - Reply: To PMID 26142579. PMID- 26142582 TI - Assessment of Time-dependent Changes in Semen Parameters in Infertile Men After Microsurgical Varicocelectomy. AB - OBJECTIVE: To characterize the changes in seminogram findings in infertile men after varicocelectomy. METHODS: This study included 71 consecutive infertile men who underwent microsurgical low ligation varicocelectomy and received 3 semen analyses, 1 before microsurgical varicocelectomy and again at 3 and 12 months after. Total motile sperm count (TMSC) was calculated using the following formula: [volume (mL) * concentration (millions/mL) * motility (%)]. RESULTS: Despite the lack of significant changes in the proportion of sperm with abnormal morphology, sperm concentration, motility, and TMSC in the 71 patients were significantly higher at 3 and 12 months after varicocelectomy than before surgery. However, no further improvement in these parameters at 12 months after varicocelectomy was noted compared with those at 3 months. Furthermore, when the included men were divided into 3 groups according to preoperative TMSC as <3 million, 3-9 million, and >9 million, TMSCs at 3 months after varicocelectomy in all 3 groups were significantly higher than those before varicocelectomy; however, TMSCs at 12 months after surgery in all groups were similar to those at 3 months. CONCLUSION: The level of improvement in semen parameters at 3 months after varicocelectomy may be stable at 12 months after surgery, irrespective of baseline values of TMSC. Therefore, varicocelectomy could be offered as a therapeutic option for infertile men, even for couples with an older woman, because its efficacy is evaluable at 3 months after surgery, and assisted reproductive technology could be immediately applied to ineffective cases. PMID- 26142583 TI - Intralesional Injections for Early Peyronie Disease: Standardized Assessment and Analysis of Predictive Factors for Treatment Response. AB - OBJECTIVE: To assess the outcomes of a new protocol of intralesional injections of verapamil (ILIV) to treat Peyronie disease (PD) and to look for predictors of response. METHODS: Patients followed up for PD in our center were prospectively enrolled between 2007 and 2013. The following data were collected: age, degree of curvature of the penis, Lue score (severity score of PD [0-15]), and pain (analogic Likert scale: 0-5). The protocol consisted of 1 verapamil injection per session (15 mg in 6 mL) in the main plaque using a single-puncture approach. Injections were repeated once every 3 weeks, at least 6 times. RESULTS: Sixty men were included. Mean number of injections per patient was 12.6 (+/-8.9). Average Lue scores before and after ILIV were 9.4 (+/-2) and 4.5 (+/-2; P = .05), respectively. Average penile curvatures during erection before and after ILIV were 37.3 degrees (+/-13.3) and 21 degrees (+/-13), respectively (P = .02). There were no serious side effects. At the end of follow-up, 47 patients (78%) considered themselves globally improved. Younger age was the only predictor of response to ILIV in univariate (odds ratio = 0.91; P = .04) and multivariate analyses (odds ratio = 0.87; P = .03). CONCLUSION: ILIV had a favorable impact reducing PD in 78% of patients with minimal side effects. Most patients required at least 12 injections to obtain optimal improvement. A protocol consisting of repeated courses of 6 injections using a single-puncture approach appears a valid option. Younger age was the only predictor of success. PMID- 26142584 TI - Association Between Dosage Frequency and the Treatment Outcomes of Sildenafil in Young and Middle-aged Men With Erectile Dysfunction: A Chinese, Multicenter, Observational Study. AB - OBJECTIVE: To evaluate the correlation between the dosage frequency of sildenafil and its treatment outcomes in men with erectile dysfunction (ED). METHODS: Data were from a 4-week, multicenter, observational study of men (1699), between 18 and 60 years of age, with a clinical diagnosis of ED defined as the Sexual Health Inventory for Men (SHIM) score <=21. The erectile function and quality of sexual life were evaluated at the baseline and the endpoint of sildenafil treatment (after 4 weeks) by using SHIM, Self-Esteem and Relationship Questionnaire, 36 Item Short Form Health Survey, Erection Hardness Score, and the global efficacy question. RESULTS: Nine hundred thirty-five patients were enrolled in the <=1 weekly, 573 in the 2-3 weekly, and 158 in the 4-7 weekly dosage frequency cohorts. After 4 weeks of treatment, a higher dosage frequency of sildenafil was associated with a better SHIM, Self-Esteem and Relationship Questionnaire, and 36 Item Short Form Health Survey score improvement (all P <.0001). Hyperlipidemia is a poor prognostic factor (odds ratio, 3.59; P = .04), whereas hypertension (odds ratio, 0.25; P <.01) and coronary heart disease (odds ratio, 0.56; P = .05) are sensitive to sildenafil treatment. CONCLUSION: Higher dosage frequency of sildenafil is associated with a better improvement of sexual function and quality of life of men with ED, and the concomitant treatment of hyperlipidemia is recommended. PMID- 26142585 TI - Forensic Identification for Erectile Dysfunction: Experience of a Single Center. AB - OBJECTIVE: To analyze the characteristics of forensic identification cases and evaluate the importance of integrating penile erection length, angle, and rigidity in diagnosing erectile dysfunction (ED). METHODS: Retrospective analysis of the forensic identification cases between Jan 2009 and May 2013. Correlation between ED diagnosis and nocturnal penile tumescence (NPT) test result or the site of injury was analyzed. RESULTS: In total, 148 patients came for forensic identification of sexual function because of rape charges, divorce, medical accidents, or injury: 126 of 148 (85.1%) because of injury, of which 95 (75.4%) resulted from traffic accidents. There was a significant correlation between the site of injury and ED diagnosis; pelvic fracture with urethral or perineum injury was the most common. Our data showed that ED diagnosis was in general significantly associated with NPT results. However, we also identified three cases of diagnosed organic ED with normal NPT reactions. Our analyses showed that abnormal length and/or angle of the erectile penis were contributing factors to the diagnoses in these cases. CONCLUSION: In addition to NPT test, which measures the rigidity of the erectile penis, the length and angle of the erectile penis should also be considered in diagnosing ED, particularly in the case of forensic identification of sexual function. PMID- 26142586 TI - Sickle Cell Disease in Priapism: Disparity in Care? AB - OBJECTIVE: To determine the effect of sickle cell disease (SCD) on hospital resource use among patients admitted for priapism. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample, a weighted sample of 12,547 patients was selected with a primary diagnosis of priapism from 2002 to 2011. Baseline differences for patient demographics and hospital characteristics were compared between SCD and non-SCD patients. Multivariate analysis was performed to identify the effect of SCD on length of stay, use of penile operations, blood transfusion, and cost. RESULTS: The proportion of SCD patients was 21.5%. SCD patients were younger, more often black, more likely to have Medicaid insurance, and treated more frequently in Southern urban teaching hospitals. SCD was a significant predictor of having a blood transfusion (odds ratio [OR], 16.3; P <.001), and an elongated length of stay (OR, 1.42; P <.001). SCD was associated with less penile operations (OR, 0.40; P <.001). When SCD patients did have an operation, it was performed later in the admission (mean, 0.87 vs 0.47 days; P <.001). SCD was not a significant predictor of increased cost (OR, 1.02; P = .869). CONCLUSION: SCD patients represent a demographically distinct subgroup of priapism patients with different patterns of resource use manifested by longer hospital stays and more blood transfusions. Moreover, despite evidence that immediate treatment of priapism results in improved erectile function outcomes, SCD patients had less surgical procedures for alleviation of acute priapism events. PMID- 26142587 TI - Reply: To PMID 26142586. PMID- 26142588 TI - Editorial Comment. PMID- 26142589 TI - Comparison of 2 Computed Tomography-based Methods to Estimate Preoperative and Postoperative Renal Parenchymal Volume and Correlation With Functional Changes After Partial Nephrectomy. AB - OBJECTIVE: To compare freehand scripting and semiautomated renal parenchymal volume measurements on preoperative or postoperative computed tomography scans and assess relationships between parenchymal volume loss and functional changes within the operated kidney after partial nephrectomy (PN). MATERIALS AND METHODS: Fifty patients (16 solitary kidneys, 34 bilateral kidneys) with renal tumors managed by PN with necessary studies for analysis were included. Freehand scripting and semiautomated threshold-based analysis were performed before and 4 12 months after PN to obtain preoperative normal parenchymal volumes, projected residual parenchymal volumes, and actual postoperative volumes. Glomerular filtration rate was determined by the Modification of Diet in Renal Disease 2 equation along with nuclear renal scan to provide split function for patients with 2 kidneys. Limits of agreement and Bland-Altman analyses were performed. The relationship between the amount of vascularized parenchyma preserved and renal function saved was correlated for each measurement method using Pearson correlation. RESULTS: The semiautomated method yielded estimates that were higher than freehand scripting by a mean of 14 cm(3) for estimation of preoperative normal parenchymal volume, 21 cm(3) for projected residual parenchymal volume, and 9 cm(3) for actual postoperative parenchymal volume. For the semiautomated method, correlation between the amount of normal parenchyma preserved and renal function saved was 0.52 (95% confidence interval [CI], 0.28-0.69; P <.001), and for the scripting method, correlation was 0.60 (95% CI, 0.39-0.76; P <.001). CONCLUSION: Semiautomated and freehand scripting measurements of parenchymal volumes were relatively consistent before and after PN, although the semiautomated approach tended to yield volumes that were approximately 5%-10% higher on average. Measurement of parenchymal volume changes by both approaches correlated significantly with functional changes after PN. PMID- 26142590 TI - Radical Cystectomy for Bladder Cancer in Patients With and Without a History of Pelvic Irradiation: Survival Outcomes and Diversion-related Complications. AB - OBJECTIVE: To compare survival outcomes and diversion-related complications of patients with and without a history of pelvic irradiation who underwent radical cystectomy. PATIENTS AND METHODS: Three hundred sixty-four patients underwent radical cystectomy for bladder cancer (BCa) from July 2001 to September 2013. Thirty-seven patients (10%) had a history of pelvic irradiation, and 327 (90%) did not. The Kaplan-Meier method and Cox regression models were applied to evaluate survival outcomes. Diversion-related complications were tabulated. RESULTS: The proportion of non-organ-confined disease was numerically higher in irradiated than in nonirradiated patients (18 of 37 [49%] vs 117 of 327 [36%] patients, P = .1). The difference in the proportion of T4 disease between the 2 groups was statistically significant (13 of 37 [35%] irradiated vs 37 of 327 [11%] nonirradiated patients, P = .005). Pelvic lymph node dissection could not be performed in 7 of 37 irradiated patients. A nonurothelial carcinoma histology was more frequent in irradiated than in nonirradiated patients (5 of 37 [14%] vs 19 of 327 [6%], P = .003). At 3 years, BCa recurrence-free survival estimates were 70 +/- 9% and 77 +/- 3% (log-rank P = .5), and BCa-specific survival estimates were 64 +/- 9% and 69 +/- 3% (log-rank P = .4), for irradiated and nonirradiated patients, respectively. In multivariate analysis, a history of pelvic irradiation was not predictive of BCa recurrence or BCa-specific death. Rates of diversion-related complications did not differ between the 2 groups. CONCLUSION: BCa patients with a history of pelvic irradiation present with more advanced disease. Surgery remains difficult in this group of patients as pelvic lymph node dissection is omitted in approximately 1 of 5 patients. Within limitations, prior pelvic irradiation is not predictive of survival outcomes. PMID- 26142591 TI - Editorial Comment. PMID- 26142592 TI - Reply: To PMID 26142590. PMID- 26142593 TI - Added Value of Multiparametric Ultrasonography in Magnetic Resonance Imaging and Ultrasonography Fusion-guided Biopsy of the Prostate in Patients With Suspicion for Prostate Cancer. AB - OBJECTIVE: To analyze whether magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided biopsy detects more and clinical significant prostate cancer (PCa) in comparison to conventional transrectal US-guided prostate biopsy (PBX) and to investigate if multiparametric (mp) US during MRI-US fusion can further characterize mpMRI-suspected lesions according to the prostate MRI reporting and data system (PI-RADS). METHODS: From January 2012 to January 2014, 169 patients with a median of 2 negative conventional PBX and/or initially or consistently elevated prostate-specific antigen levels were prospectively included and underwent 3 T mpMRI. Real-time MRI-US fusion scan was used to biopsy the mpMRI targeted lesions (n = 316). Scanning by mpUS, including B-mode, power Doppler, strain elastography, and contrast-enhanced US was performed to further characterize those lesions and to score by US modalities resulting in an mpUS score. Afterward, a conventional 10-core PBX was performed. PCa detection based on the results of targeted and conventional PBX was estimated. Performances of single US modalities were analyzed. The mpUS score was also investigated for PCa and PI-RADS score prediction. RESULTS: Among 169 patients, 71 PCa (42%) were detected. From these 71 cases, clinically significant PCa (Gleason score >=7) were detected exclusively by MRI-US fusion in 31 from 46 cases (67.4%). The highest sensitivity was observed in contrast-enhanced US (85%) and elastography (80%). The mpUS score predicts PCa and PI-RADS score with an overall accuracy of 86% and 80%, respectively. CONCLUSION: MRI-US fusion-guided PBX detects more clinically significant PCa compared with conventional TRUS. The mpUS score correlates with PI-RADS in PCa prediction. PMID- 26142594 TI - Recovery of Urinary Continence After Radical Prostatectomy Using Early vs Late Pelvic Floor Electrical Stimulation and Biofeedback-associated Treatment. AB - OBJECTIVE: To compare the early vs late use of pelvic floor electrical stimulation (FES) plus biofeedback (BF) in terms of time to recovery and rate of continence after radical prostatectomy (RP). MATERIALS AND METHODS: Between April 2007 and April 2012, a total of 120 patients who underwent RP were prospectively included in the study. In group 1 (60 cases), we included patients who presented a urinary leakage weight >=50 g for 24 hours, 14 days after catheter removal. In group 2 (60 cases), we included patients who continued to present a urinary leakage weight >=50 g for 24 hours, 12 months after surgery. In both groups, patients were prospectively submitted to the same program of BF+FES. RESULTS: Mean leakage weight became significantly lower (P <.002) in group 1 than in group 2 starting from visit 1 (2 weeks) through visit 7 (24 weeks). However, a significant difference (P <.05) between the 2 groups in terms of percentage of continent patients was achieved only at 2 weeks (group 1 = 20%; group 2 = 0%) and 4 weeks (group 1 = 66.7%; group 2 = 46.7%). The objective continence rate 6 months after the beginning of treatment was 96.7% in group 1 and 91.7% in group 2. CONCLUSION: In our experience, the treatment with BF and FES has a significant positive effect on the recovery of urinary continence independently to the time in which it is used (early vs delayed). This protocol might represent a noninvasive method for all patients undergoing RP, also in a 12-month interval from surgery. PMID- 26142595 TI - Reply: To PMID 26142594. PMID- 26142596 TI - Editorial Comment. PMID- 26142597 TI - Urinary Bladder Contractility Revisited. Correlation of Noninvasively and Invasively Measured Contractility Parameters in Patients Eligible for Transurethral Resection of the Prostate. AB - OBJECTIVE: To validate a noninvasively estimated measure of urinary bladder contractility by correlating it with 3 existing invasive contractility parameters and to compare and correlate those invasive parameters. METHODS: A group of 74 patients, recruited in 3 different hospitals, and eligible for transurethral resection of the prostate on clinical grounds, were noninvasively studied preoperatively using the condom catheter method. The maximum condom pressure pcond.max measured during a mechanical interruption of flow rate was considered an estimate of urinary bladder contractility and compared to conventional contractility parameters calculated from preoperative (invasive) pressure-flow studies. RESULTS: The highest correlations were found between the invasive parameters. The correlation between the noninvasive parameter on the one hand and the invasive parameters on the other hand was lower, but mostly significant. In a number of patients, pcond.max underestimated the isovolumetric bladder pressure. The underestimated patients were more obstructed than those who were not underestimated and had a higher (invasively measured) contractility. When the underestimated patients were deselected, the correlation between the noninvasive pcond.max and the invasive parameters in the remaining 52 patients was higher. CONCLUSION: The 4 tested contractility parameters represent different aspects of urinary bladder contractility. Nevertheless, there was a significant correlation among them supporting the concept of a common basis, that is, detrusor contractility. The invasive contractility parameter bladder contractility index overestimated contractility in patients with lower urinary tract symptoms and/or benign prostatic enlargement. A modified parameter is suggested. PMID- 26142598 TI - Association Between High-sensitivity C-reactive Protein and Lower Urinary Tract Symptoms in Healthy Korean Populations. AB - OBJECTIVE: To investigate the association between high-sensitivity C-reactive protein (hs-CRP) and lower urinary tract symptoms in healthy middle-aged men. MATERIALS AND METHODS: A total of 4256 ostensibly healthy native Korean men between the ages of 40 and 65 years who voluntarily underwent medical checkup were enrolled. The participants' demographics were collected, including International Prostate Symptom Score, hs-CRP, various metabolic risk factors, and prostate volume (PV). Multivariate regression analyses were performed to investigate the relationship between hs-CRP and lower urinary tract symptoms after adjustment for age, PV, metabolic syndrome, and body mass index (BMI). RESULTS: Data obtained from 3539 men were analyzed. The mean age was 51.75 +/- 7.01 years, and the mean C-reactive protein (CRP) level was 0.137 +/- 0.256 mg/L. Correlation analysis after adjustment for age, PV, and BMI revealed that CRP only correlated with storage symptoms (coefficient = 0.044, P value = .007) and not voiding symptoms. Multivariate analysis using the full model revealed that age and CRP were positively correlated with storage symptoms (P <.001 and .008, respectively). Multivariate analysis using a stepwise model revealed that age, CRP, and triglycerides were positively correlated with storage symptoms (P <.001, .007, and .022, respectively) and BMI was negatively correlated with storage symptoms (P = .023). CONCLUSION: In healthy men, hs-CRP was independently correlated with storage symptoms after adjustment for age, BMI, PV, and metabolic risk factors. Subclinical inflammation might play a role in the pathophysiology of storage symptoms. PMID- 26142599 TI - Photoselective Vaporization of the Prostate in Men With Refractory Urinary Retention. AB - OBJECTIVE: To assess the efficacy of photoselective vaporization of the prostate (PVP) and the predictive factors of treatment failure in patients with refractory urinary retention. MATERIALS AND METHODS: From January 2006 to December 2013, we prospectively included all patients treated by PVP preoperatively catheterized for urinary retention. The primary end point was the number of patients free of indwelling catheters 3 months after the procedure. Univariate and multivariate analyses were performed to identify the predictive factors of treatment failure. RESULTS: One hundred fifty-two patients were included in the final analysis. The percentage of patients free of indwelling catheters was 91.5% 3 months after PVP. Two factors were identified as predictive of treatment failure at 3 months in multivariate analysis: a smaller preoperative ultrasonographic prostate volume (UPV; odds ratio [OR] = 0.91; P = .008) and a higher volume of primary urinary retention (OR = 1.03; P = .003). Forty-two patients (27.6%) required early recatheterization within 7 days after surgery. Smaller UPV was the only predictive factor of treatment failure in the early postoperative in multivariate analysis (OR = 0.97; P = .01). CONCLUSION: Nearly one-third of patients treated for refractory urinary retention fail the first trial without catheter after PVP, but 91.5% are free of indwelling catheter 3 months after surgery. A smaller preoperative UPV and a higher retention volume were predictive of PVP failure in patients with preoperative indwelling catheters. PMID- 26142600 TI - Adenotonsillectomy Normalizes Hormones and Urinary Electrolytes in Children With Nocturnal Enuresis and Sleep-Disordered Breathing. AB - OBJECTIVE: To assess (1) plasma levels of antidiuretic hormone (ADH) and brain natriuretic peptide (BNP) and urinary levels of electrolytes in children with sleep disordered breathing (SDB), with or without nocturnal enuresis (NE), and (2) the effect of adenotonsillectomy (T&A) on urinary electrolytes and the secretion of ADH and BNP in children with NE and SDB. We previously reported post T&A improvements in plasma levels of BNP and ADH in children with SDB and NE. However, the differences in plasma concentration of these hormones in SDB children with and without NE, and their relationships with urinary electrolytes, have not yet been addressed. METHODS: This prospective study compared concentrations of urinary electrolytes and plasma ADH and BNP in (1) children with SDB and NE (study group) and an age- and sex-matched control group of children with SDB without NE, and (2) the study group before and 1-month after T&A. RESULTS: Compared with the control group (n = 31), the study group (n = 37) exhibited significantly lower ADH (P = .04) and higher BNP (P = .009) plasma levels. The differences in urinary electrolytes were not significant. Post-T&A, the study group showed significantly decreased BNP (P = .018), urinary sodium-to creatinine ratio (P = .02), and urinary calcium-to-creatinine ratio (P = .007) compared with the pre-T&A values. Post-T&A changes in urinary calcium were significantly correlated with changes in sodium excretion (P = .002) and in plasma levels of BNP (P <.001). CONCLUSION: The presence of NE is associated with altered ADH and BNP levels in children with SDB. T&A led to normalization of ADH and BNP, probably through a calcium- and sodium-dependent mechanism. PMID- 26142601 TI - Laparoscopic Nephron-sparing Surgery for Metanephric Adenoma in Children: A Report of 2 Cases. AB - Metanephric adenoma (MA) is an epithelial benign tumor of the kidney and very rare in children. Here we present 2 cases of MA treated by laparoscopic nephron sparing surgery in children. To the best of our knowledge, we report the first cases of laparoscopic nephron-sparing surgery for MA in children. PMID- 26142602 TI - Revision Techniques After Artificial Urinary Sphincter Failure in Men: Results From a Multicenter Study. AB - OBJECTIVE: To compare the results of various single-component artificial urinary sphincter (AUS) revision techniques for continued/recurrent stress urinary incontinence (SUI). Although AUS placement for male SUI has a high rate of success, revisions may be performed for mechanical failure of an isolated component or continued/recurrent SUI. MATERIALS AND METHODS: From 1993 to 2012, 90 AUS revisions including urethral cuff downsizing (19), pressure-regulating balloon replacement (18), cuff repositioning (11), or tandem cuff placement (42) were performed at 2 institutions. End points included reoperation, incontinence failure, and urethral erosion. The Kruskal-Wallis test was used to compare continuous variables, and the log-rank test was used to compare Kaplan-Meier curves. RESULTS: Mean age was 70.2 years, and median follow-up was 33.6 months. Median time to revision was 28.9 months. Tandem cuff placement was associated with a lower rate of incontinence failure (P = .02), whereas cuff repositioning was associated with a higher rate of incontinence failure (P = .02). An increased rate of mechanical failure was observed with cuff downsizing (P = .01). Among options for revision (1) cuff downsizing is associated with a higher rate of mechanical failure, and (2) cuff repositioning with the same size is associated with a higher rate of incontinence failure, whereas (3) tandem cuff placement is associated with a lower rate of recurrent SUI compared to other types of AUS revision. CONCLUSION: Cuff repositioning is associated with an increased rate of persistent incontinence after AUS revision whereas tandem cuff placement is associated with a lower rate of recurrent or persistent incontinence. PMID- 26142603 TI - National Patterns of Urethral Evaluation and Risk Factors for Urethral Injury in Patients With Penile Fracture. AB - OBJECTIVE: To examine the epidemiology and timing of penile fracture, patterns of urethral evaluation, and risk factors for concomitant urethral injury. MATERIALS AND METHODS: The National Inpatient Sample (2003-2011) was used to identify patients with penile fractures. Clinical data included age, race, comorbidity, insurance, hospital factors, timing, hematuria, and urinary symptoms. Rates of formal urethral evaluation (cystoscopy or urethrogram) and urethral injury were calculated. Multivariate logistic regression was used to identify predictors of urethral evaluation and risk factors for urethral injury. RESULTS: A weighted population of 3883 patients with penile fracture was identified. Presentations during weekends (37%) and summers (30%) were overrepresented (both P <.001). Urethral evaluation was performed in 882 patients (23%). Urethral injury was diagnosed in 813 patients (21%) with penile fracture. There was an increased odds of urethral evaluation with hematuria (odds ratio [OR] = 2.99; 95% confidence interval [CI], 1.03-8.73; P = .045) and a decrease for Hispanics (OR = 0.42; 95% CI, 0.22-0.82; P = .011). Older age (32-41 years: OR = 1.84; 95% CI, 1.07-3.16; P = .027; >41 years: OR = 2.25; 95% CI, 1.25-4.05; P = .007), black race (OR = 1.93; 95% CI, 1.12-3.34; P = .018), and hematuria (OR = 17.03; 95% CI, 3.20 90.54; P = .001) were independent risk factors for urethral injury. CONCLUSION: Penile fractures, which occur disproportionately during summer and weekends, were associated with a 21% risk of urethral injury. Urethral evaluations were performed in a minority of patients. Even in patients with hematuria, 55% of patients underwent formal urethral evaluation. On multivariate analysis of patients with penile fracture, hematuria as well as older age and black race were independently associated with concomitant urethral injury. PMID- 26142604 TI - Reply: To PMID 26142603. PMID- 26142605 TI - Editorial Comment. PMID- 26142606 TI - Laparoscopic Intravesical Detrusorrhaphy With Ureteral Plication for Megaureter: A Novel Technique. AB - INTRODUCTION: To demonstrate the novel technique of laparoscopic intravesical detrusorrhaphy with ureteral plication for megaureter. TECHNICAL CONSIDERATIONS: From December 2012 to June 2014, 11 patients with primary unilateral megaureter underwent laparoscopic intravesical detrusorrhaphy with ureteral plication. By a transvesicoscopic approach using a 3-port technique, the ureter was mobilized and plicated with a 6F Foley catheter. After dissection of the bladder mucosa in a semilunar shape, the detrusor was incised vertically and repaired underneath the mobilized ureter to create a submucosal tunnel. The ureter was covered with bladder mucosa, and the ureteral orifice was anastomosed to its orthotopic neoureteric orifice. The mean age of the included patients at the time of surgery was 9.18 years (range, 12 months-24 years). All surgeries were successfully completed without open conversion, with a mean operation time of 214 minutes including preoperative evaluation. All patients tolerated the procedure without any complications. Within the mean follow-up duration of 12.6 months (range, 5-24 months), no complications related to the surgery were reported, and no vesicoureteral reflux was detected in the operated side on postoperative voiding cystourethrography. The distal ureteral diameter was significantly reduced (from 21.1 to 11.6 mm), and the grade of hydronephrosis was decreased on postoperative ultrasonography without deterioration of renal function. CONCLUSION: In this study, laparoscopic intravesical detrusorrhaphy with ureteral plication demonstrated successful short-term outcomes in management of megaureter in children and adults. Our technique can be an effective and feasible surgical option in the treatment of megaureter. PMID- 26142607 TI - Transvaginal Excision of Bilateral Single Ureteral Stumps of Refluxing Ectopic Ureters in an Adult Female With Urinary Incontinence. AB - OBJECTIVE: To report a novel surgical technique of transvaginal excision of bilateral refluxing single ureteral stumps in an adult female, with emphasis on the technique, the difficulties of the procedure, and other surgical consideration such as bladder neck reconstruction and use of pubovaginal sling in patients with these congenital anomalies. METHODS: The procedure starts with cystoscopy for identification and catheterization of the orifices of remnant ectopic ureters. This is important to facilitate close dissection of ureteral stumps without the risk of vascular and visceral injury. A wide inverted U incision is made in the anterior vaginal wall to complete the dissection and excision for the remnants of ectopic ureters followed by water-tight closure for each ureterourethral junction. The procedure is completed with bladder neck reconstruction and pubovaginal sling with autologous rectus fascia. RESULTS: The operative time was 3 hours, estimated blood loss was 50 mL, and hospital stay was 1 day. There were no intraoperative complications, and the patient went home on catheter drainage for 10 days with prophylactic antibiotics and anticholinergic medications. One-year follow-up showed her global satisfaction of 80%, and she uses one small pad per day as needed. She reported no more recurrent urinary tract infections, no difficulty of voiding, and no pain. CONCLUSION: Transvaginal approach for excision of bilateral infravesical remnant of ectopic ureters in an adult female is feasible. Successful surgical outcomes require bladder neck reconstruction and use of autologous rectus fascia in patient with bilateral single-system ectopic ureters, as the sphincteric mechanism of the bladder neck is absent. PMID- 26142608 TI - Laparoscopically Guided External Transanastomotic Stenting in Dismembered Pyeloplasty: A Safe Technique. AB - OBJECTIVE: To describe a technique for insertion of external transanastomotic stents during laparoscopic dismembered pyeloplasty in children of all age-groups. To analyze stent-associated complications and changes in differential renal function (DRF). PATIENTS AND METHODS: A retrospective study was performed of all patients up to 18 years of age undergoing laparoscopic pyeloplasty at our institution between March 2004 and December 2013. We analyzed patients in whom an external transanastomotic stent was placed using a specially constructed semicircular spear. Medical records were reviewed for stent-associated complications such as bleeding, stent dislocation, stent obstruction, and urinary tract infection. Additionally required secondary surgical procedures and changes in DRF were assessed. RESULTS: A total of 150 patients (155 renal units [RU]) were included in the study, with a median patient age of 22 months (range, 1 214). Stents were removed after a median time of 7 days (range, 3-21). Stent associated complications were observed in a total of 11 patients (12 RU), consisting of stent dislocations (6 RU), stent obstructions (3 RU), and persistent percutaneous leakage along the stent (1 RU) or after stent removal (2 RU). Stent-associated complications required a secondary surgical procedure in 4 RU. Neither significant blood loss nor urinary tract infection was associated with external transanastomotic stent placement. DRF did not change significantly after the procedure. CONCLUSION: External transanastomotic stenting during laparoscopic dismembered pyeloplasty using a specially constructed semicircular spear is a safe technique associated with a low complication rate and only rarely requires secondary surgical procedures for stent-related complications. This technique makes an additional anesthesia for stent removal unnecessary, as it is required for internal urinary diversion. PMID- 26142609 TI - Metastasis of Prostate Adenocarcinoma to the Testis. PMID- 26142610 TI - Transcaval Ureter: Multidetector Computed Tomography Demonstration. AB - Transcaval ureter is a rare congenital anomaly characterized by an inferior cava vein duplication producing a vascular ring around the right ureter, usually determining hydroureteronephrosis. The knowledge of this vascular anomaly on imaging examinations permits to avoid erroneous diagnosis of retroperitoneal masses or adenopathy and preoperatively advise the surgeon of potential sources of complications. We describe a case of transcaval ureter studied with multidetector computed tomography. To our knowledge, this is the first case in which computed tomography multiplanar and volume-rendering reconstructions show this rare anomaly. PMID- 26142611 TI - Anti-anxiety efficacy of Sudarshan Kriya Yoga in general anxiety disorder: A multicomponent, yoga based, breath intervention program for patients suffering from generalized anxiety disorder with or without comorbidities. AB - BACKGROUND: Surdashan Kriya Yoga (SKY) is a procedure that in various studies, has shown evidences of efficacy in alleviating Depression and Anxiety disorders, but in Europe and USA it has not been studied yet on a Caucasian population as an adjunct therapy for psychiatric Disorders. METHODS: The study involved a sample of consenting women and men (n = 69) who received SKY therapy for a six-month time period. They were assessed at recruitment, after two weeks, after three months and after six months using Hamilton Rating Scale for Anxiety (HRSA), Hamilton Rating Scale for Depression (HRSD), Zung Self-Rating Anxiety Scale (ZSAS), Zung Self-Rating Depression Scale (ZSDS) and Symptom Checklist-90 (SCL 90). RESULTS: All the analyses have shown that SKY therapy significantly reduces the scores of Anxiety and Depression. This is plain, especially after the initial SKY treatment, which is followed by a long plateau phase that seems to verge on no Anxiety/Depression scores. It was found that SKY effects lead to a significant convergence between the self-assessment (Zung Self-Rating Scale) and hetero assessment (Hamilton Rating Scale). LIMITATIONS: The study should be replicated on a larger clinical sample in a controlled trial to learn more about the effectiveness of SKY Protocol. CONCLUSIONS: Participation in SKY adjunct therapy ten days intense workshop and follow-ups, coupled with daily individual and independent practice of a simplified protocol of breathing techniques (30 min), can lead to significant reduction in levels of Anxiety and Depression. PMID- 26142612 TI - Antidepressants worsen rapid-cycling course in bipolar depression: A STEP-BD randomized clinical trial. AB - BACKGROUND: The use of antidepressants in rapid-cycling bipolar disorder has been controversial. We report the first randomized clinical trial with modern antidepressants on this topic. METHODS: As part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we analyzed, as an a priori secondary outcome, rapid cycling as a predictor of response in 68 patients randomized to continue vs. discontinue antidepressant treatment, after initial response for an acute major depressive episode. Outcomes assessed were percent time well and total number of episodes. All patients received standard mood stabilizers. RESULTS: In those continued on antidepressants (AD), rapid cycling (RC) subjects experienced 268% (3.14/1.17) more total mood episodes/year, and 293% (1.29/0.44) more depressive episodes/year, compared with non-rapid cycling (NRC) subjects (mean difference in depressive episodes per year RC vs. NRC was 0.85 +/- 0.37 (SE), df = 28, p = 0.03). In the AD continuation group, RC patients also had 28.8% less time in remission than NRC patients (95% confidence intervals (9.9%, 46.5%), p = 0.004). No such differences between RC and NRC subjects were seen in the AD discontinuation group (Table 1). Analyses within the rapid-cycling subgroup alone were consistent with the above comparisons between RC and NRC subjects, stratified by maintenance antidepressant treatment, though limited by sample size. CONCLUSIONS: In an a priori analysis, despite preselection for good antidepressant response and concurrent mood stabilizer treatment, antidepressant continuation in rapid-cycling was associated with worsened maintenance outcomes, especially for depressive morbidity, vs. antidepressant discontinuation. PMID- 26142613 TI - Cu-nanoparticles ecotoxicity--explored and explained? AB - The nano-form of copper (Cu-NPs) is already extensively used. In this paper the toxic effect of Cu in the worm Enchytraeus crypticus (Oligochaeta: Enchytraeidae) was assessed following exposure to (1) Cu-salt: freshly spiked soil with copper nitrate, (2) Cu-NPs: freshly spiked soil with Cu nanoparticles (80nm), and (3) Cu field: historically Cu contaminated soil (80years ago). Our main aims were to compare the three different exposure regimes and respective toxicity, and to determine how the oxidation state of the Cu and dissolution state of the particles differed. Characterization of in situ-exposure included identification of oxidation states with synchrotron generated X-ray absorption near-edge spectroscopy (XANES) analysis, activity of free Cu(2+) in soil-solution (Ion Selective Electrode), and the relative distribution of the labile Cu-fractions (Sequential Extraction). Freshly spiked Cu-salt was the most toxic for reproductive output of the worms, followed by Cu-NPs and then Cu-field. XANES indicated only one oxidation state (II) in Cu-salt and Cu-field soil, whereas in Cu-NPs soil it was present in all oxidation states (0, I and II). The partial oxidation of the Cu-NPs (in soil) was evident and with limited dissolution. PMID- 26142614 TI - Predicting aquatic toxicities of chemical pesticides in multiple test species using nonlinear QSTR modeling approaches. AB - In this study, we established nonlinear quantitative-structure toxicity relationship (QSTR) models for predicting the toxicities of chemical pesticides in multiple aquatic test species following the OECD (Organization for Economic Cooperation and Development) guidelines. The decision tree forest (DTF) and decision tree boost (DTB) based QSTR models were constructed using a pesticides toxicity dataset in Selenastrum capricornutum and a set of six descriptors. Other six toxicity data sets were used for external validation of the constructed QSTRs. Global QSTR models were also constructed using the combined dataset of all the seven species. The diversity in chemical structures and nonlinearity in the data were evaluated. Model validation was performed deriving several statistical coefficients for the test data and the prediction and generalization abilities of the QSTRs were evaluated. Both the QSTR models identified WPSA1 (weighted charged partial positive surface area) as the most influential descriptor. The DTF and DTB QSTRs performed relatively better than the single decision tree (SDT) and support vector machines (SVM) models used as a benchmark here and yielded R(2) of 0.886 and 0.964 between the measured and predicted toxicity values in the complete dataset (S. capricornutum). The QSTR models applied to six other aquatic species toxicity data yielded R(2) of >0.92 (DTF) and >0.97 (DTB), respectively. The prediction accuracies of the global models were comparable with those of the S. capricornutum models. The results suggest for the appropriateness of the developed QSTR models to reliably predict the aquatic toxicity of chemicals and can be used for regulatory purpose. PMID- 26142617 TI - Fifteen years: looking back and looking forward. PMID- 26142615 TI - Chronic Pancreatitis with Acinar-Ductal Metaplasia and Ductal Dysplasia in a Horse. AB - A 16-year-old Friesian gelding with relapsing colic was humanely destroyed during diagnostic laparotomy due to suspected abdominal neoplasia. On post-mortem examination, the pancreas appeared as a firm mass (20 * 8 * 8 cm). The cut surface had a lobular structure with multiple cavities. Histological examination revealed severe chronic fibrosing pancreatitis with acinar-ductal metaplasia and duct dysplasia, which was considered to be the cause of the recurrent colic. Formation of tubular complexes within a background of acinar-ductal metaplasia is similar to the regressive lesions detected in the human pancreas in the context of inflammation, duct obstruction, cystic fibrosis and neoplasia. Pancreatic acinar-ductal metaplasia and ductal dysplasia are considered to be preneoplastic conditions in man and in the mouse. PMID- 26142618 TI - Evaluation of service quality in family planning clinics in Lusaka, Zambia. AB - OBJECTIVE: To determine the quality of contraceptive services in family planning clinics in Lusaka, Zambia, using a standardized approach. STUDY DESIGN: We utilized the Quick Investigation of Quality, a cross-sectional survey tool consisting of a facility assessment, client-provider observation and client exit interview, in public-sector family planning clinics. Data were collected on availability of seven contraceptive methods, information given to clients, interpersonal relations between providers and clients, providers' technical competence and mechanisms for continuity and follow-up. RESULTS: Data were collected from five client-provider observations and client exit interviews in each of six public-sector family planning clinics. All clinics had at least two contraceptive methods continuously available for the preceding 6 months. Most providers asked clients about concerns with their contraceptive method (80%) and told clients when to return to the clinic (87%). Most clients reported that the provider advised what to do if a problem develops (93%), described possible side effects (89%), explained how to use the method effectively (85%) and told them when to come for follow-up (83%). Clients were satisfied with services received (93%). CONCLUSION(S): This application of the Quick Investigation of Quality showed that the participating family planning clinics in Lusaka, Zambia, were prepared to offer high-quality services with the available commodities and that clients were satisfied with the received services. Despite the subjective client satisfaction, quality improvement efforts are needed to increase contraceptive availability. IMPLICATIONS: Although clients perceived the quality of care received to be high, family planning service quality could be improved to continuously offer the full spectrum of contraceptive options. The Quick Investigation of Quality was easily implemented in Lusaka, Zambia, and this simple approach could be utilized in a variety of settings as a modality for quality improvement. PMID- 26142619 TI - In vivo release of levonorgestrel from Sino-implant (II) - an innovative comparison of explant data. AB - OBJECTIVES: Measuring the amount of progestin remaining in contraceptive implants used for different lengths of time provides useful information on in vivo release kinetics including change over time. We compared estimated in vivo levonorgestrel (LNG) release rates derived from Sino-implant (II) explants with similar data from removed Jadelle. STUDY DESIGN: We measured LNG remaining in 44 sets of Sino implant (II) used for up to 7 years and removed in four Chinese clinics. Results were compared with published data for Jadelle explants used for up to 36 months. We estimated and compared monthly and daily LNG release rates for the two products using prediction models for drug release. We also estimated the dissolution profile similarity factor, f2, for LNG release. RESULTS: Both Sino implant (II) and Jadelle release approximately 30% of total LNG load after 3 years. Results of fitting the data to a biologically plausible modified Higuchi prediction model indicate comparable release through 3 years. An estimated similarity factor of 80.6 (90% confidence interval: 70.8-85.7) indicates similarity in the dissolution profiles of the two implants. CONCLUSIONS: LNG release in vivo measured through explant analysis suggest that Sino-implant (II) and Jadelle may perform similarly through 3 years of use and could remain highly effective beyond this time point. These results align with published data for Jadelle and Sino-implant (II) showing high effectiveness for 5 years. Ongoing clinical studies comparing the products over 5 years present an opportunity to verify this supportive measure of clinical effectiveness. IMPLICATIONS: This innovative approach provides evidence that Sino-implant (II) may perform clinically similarly to Jadelle over 3 years and remain a highly effective contraceptive beyond this time point. Data from explant analyses show promise for investigating the equivalence of elusion profiles of contraceptive implants. PMID- 26142620 TI - A prospective, non-randomized study of home use of mifepristone for medical abortion in the U.S. AB - OBJECTIVE: To determine the acceptability of taking mifepristone at home for early medical abortion in the United States. STUDY DESIGN: This prospective, non randomized, open-label study at six Planned Parenthood centers gave women with pregnancies up to 63 days' gestation seeking medical abortion the choice of taking mifepristone in the center or at home. Participants were interviewed at a follow-up visit 1-2 weeks after mifepristone administration to assess their experience with the option they selected. RESULTS: Four-hundred women were enrolled between April 2013 and June 2014 of which 32% (n=128) chose to take mifepristone at home. Abortion success rates did not differ between home and center users (96% and 97%). Among home users, 82% reported taking the mifepristone at the time they planned with their provider and no participant took it after 63 days' gestation. The most common reason cited for selecting home use was scheduling flexibility and significantly more home users took misoprostol on the weekend (50% vs. 36%, p=.02). Home users were more likely than center users to report missing no days of work due to the abortion (47% vs. 28%, p=.08). Ninety-nine percent of home users reported that they would take mifepristone at home again and 96% would recommend home use to a friend. Offering this option did not increase the service delivery burden on study providers, who would recommend home use in the future for most participants. CONCLUSIONS: Home use of mifepristone is a highly acceptable practice for which there is current demand, and it should be offered as part of routine medical abortion services. IMPLICATIONS: Offering the option of home use of mifepristone to medical abortion patients can provide women and clinics with more flexibility while maintaining a safe, effective and acceptable service. These results provide support for telemedicine or pharmacy distribution. PMID- 26142621 TI - The costs of accessing abortion in South Africa: women's costs associated with second-trimester abortion services in Western Cape Province. AB - OBJECTIVES: To assess women's costs of accessing second-trimester labor induction and dilation and evacuation (D&E) services at four public hospitals in Western Cape Province, South Africa. STUDY DESIGN: From April to August 2010, in interviews immediately after completion of their abortion, we asked women about specific direct and indirect costs incurred. We collected information on recurring costs (i.e., per visit) and one-time expenditures and calculated total costs. RESULTS: In total, 194 patients participated (136 D&E; 58 induction). Their median age was 26; 37.6% reported being employed or doing paid work. Most (73.2%) women visited two different facilities, including the study facility, while seeking the procedure. Induction women reported a median of three required visits [interquartile range (IQR) 2.0-3.0] to the study facility, while D&E women reported two required visits [IQR 1.0-2.0]. Twenty-seven percent of women missed work due to the procedure, and few (4.6%) paid for childcare. At each visit, almost all women (180, 92.8%) paid for transportation costs and reported additional one-time costs (177, 91.2%) such as sanitary supplies or doctor's fees. The total median cost incurred per woman was $21.23 [IQR 11.94-44.68]. Roughly half (49.0%) received help with these costs. CONCLUSIONS: Although technically offered freely or low cost in the public sector, women accessing second-trimester abortion lost income and incurred costs for transport, fees, supplies and childcare. Their total costs could be reduced by minimizing the number of required visits to facilities and freely offering supplies such as sanitary pads and pregnancy tests. IMPLICATIONS: Limited access to second trimester, safe abortion services in South Africa may result in some women incurring unnecessary costs. Women make multiple visits in attempting to obtain an abortion, often because of facility or health systems requirements, and incur costs for lost income, child care, transport, fees and supplies. PMID- 26142622 TI - Polypeptide from Chlamys farreri suppresses ultraviolet-B irradiation-induced apoptosis through restoring ER redox homeostasis, scavenging ROS generation, and suppressing the PERK-eIF2a-CHOP pathway in HaCaT cells. AB - OBJECTIVE: The aim of this study was to investigate the effect of polypeptide from Chlamys farreri (PCF) on ultraviolet B (UVB) irradiation-induced apoptosis in human keratinocyte HaCaT cells. METHODS: HaCaT cells were treated with 20 mJ/cm(2) UVB irradiation for 18 h. The cell viability was measured by MTT assay, and apoptosis was detected with Hoechst 33258 staining and caspase-3 activity detection. Protein expression levels were assessed by Western blot analysis, and the intracellular ROS levels were also measured. RESULTS: Our results from the MTT assay showed that UVB irradiation significantly declined the viability of HaCaT cells, which could be restored by PCF treatment. PCF decreased the apoptosis rate in HaCaT cells treated with UVB irradiation. Moreover, PCF increased the expression levels of PDI and Ero-1a, and scavenged the intracellular ROS. Furthermore, PCF inhibited the expressions of GRP78, p-PERK, p eIF2a, and CHOP, and suppressed the ER stress-induced apoptosis, in UVB irradiated HaCaT cells. In addition, the ROS scavenging effect of 4-PBA was less potent than PCF, indicating that ER stress-related ROS production contribute partially to the total ROS level, and ER was not the only target of PCF treatment. CONCLUSIONS: Our results indicate that PCF inhibits UVB irradiation induced apoptosis through restoring ER redox homeostasis and suppressing the PERK eIF2a-CHOP pathway. These findings provide evidence for the application of PCF in the protection of skin from UV irradiation. PMID- 26142623 TI - Reliability and validity of 12-item Short-Form health survey (SF-12) for the health status of Chinese community elderly population in Xujiahui district of Shanghai. AB - BACKGROUND: The 12-item Short-Form Health Survey (SF-12) is the abridged practical version of SF-36. AIMS: This cross-sectional study was aimed to assess the reliability and validity of SF-12 for the health status of Chinese community elderly population. METHODS: The Chinese community elderly people in Xujiahui district of Shanghai were investigated. The internal consistency reliability was assessed using Cronbach's alpha and split-half reliability coefficients. Construct validity was analyzed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Spearman's correlation coefficient (rho) was used for the evaluation of criterion, convergent, and discriminant validity with Spearman's rho >= 0.4 as satisfactory. Comparisons of the SF-12 summary scores among populations that differed in demographics were performed for discriminant validity. RESULTS: Total 1343 individuals aged >=60 and <85 years old (response rate: 91.3 %) were analyzed. The Cronbach's alpha value (0.910) and the split half reliability coefficient (0.812) reflected satisfactory internal consistency reliability of SF-12. EFA extracted a two-factor model (physical and mental health). About 60.7 % of the total variance was explained by the two factors. CFA showed that the two-factor solution provided a good fit to the data. Good convergent validity and discriminant validity of SF-12 were proved by the correction analyses (Spearman's rho > 0.4) and the comparisons of the SF-12 summary scores among populations (P < 0.05). SF-12 summary scores were significantly correlated with the SF-36 summary scores (Spearman's rho > 0.4, P < 0.05). CONCLUSIONS: In conclusion, SF-12 had satisfactory reliability and validity in measuring health status of Chinese community elderly population in Xujiahui district of Shanghai. PMID- 26142625 TI - Nanocellulose coated with various free fatty acids can adsorb fumonisin B1, and decrease its toxicity. AB - The aim of this study was to evaluate the adsorption and biological properties of nanocellulose coated with free fatty acids (NCCFFAs). At first, nanocellulose was synthesized by acid hydrolysis, and then separately coated with different free fatty acids (FFAs), including lauric acid, alpha linoleic acid, oleic acid, and palmitic acid. Next, the serial concentrations of NCCFFAs (1, 10, 100, and 1000 MUg/mL) was separately added to fumonisin B1 (FB1) at 1000 MUg/mL, and separately incubated at 37 degrees C for 1, 2, and 3h. Then, the percentage of adsorption was calculated. In the next experiment, the viability of mouse liver cells was measured when they exposed to serial concentrations of NCCFFAs, FFAs, and FB1. This study showed that the increase of incubation time and concentration of NCCFFAs led to increase of FB1 adsorption. Although FFAs and NCCFFAs had no remarkable toxicity, the high toxicity was observed for FB1. Importantly, the toxicity of FB1 was highly decreased, when incubated together with FFAs or NCCFFAs. These novel adsorbents, NCCFFAs, can be used together with different foodstuffs to remove FB1. PMID- 26142624 TI - Metabolic syndrome correlates poorly with cognitive performance in stroke-free community-dwelling older adults: a population-based, cross-sectional study in rural Ecuador. AB - BACKGROUND: Studies investigating a possible correlation between metabolic syndrome and cognitive decline have been inconsistent. AIMS: To determine whether metabolic syndrome or each of its components correlate with cognitive performance in community-dwelling older adults in rural Ecuador. METHODS: Stroke-free Atahualpa residents aged >=60 years were identified during a door-to-door survey. Metabolic syndrome was defined according to the International Diabetes Federation criteria. Cognition was evaluated by the use of the Montreal Cognitive Assessment (MoCA). Multivariate logistic regression models estimated the association between metabolic syndrome and each of its components with cognitive performance. RESULTS: A total of 212 persons (mean age: 69.2 +/- 7.2 years, 64 % women) were enrolled. Of these, 120 (57 %) had metabolic syndrome. Mean scores in the MoCA were 18.2 +/- 4.6 for persons with and 19 +/- 4.7 for those without metabolic syndrome. In fully adjusted logistic models, MoCA scores were not associated with metabolic syndrome (p = 0.101). After testing individual components of metabolic syndrome with the MoCA score, we found that only hypertriglyceridemia was independently associated with the MoCA score (p = 0.009). CONCLUSIONS: This population-based study showed a poor correlation of metabolic syndrome with cognitive performance after adjusting for relevant confounders. Of the individual components of metabolic syndrome, only hypertriglyceridemia correlated with worse cognitive performance. PMID- 26142626 TI - Enhanced topical delivery of hyaluronic acid encapsulated in liposomes: A surface dependent phenomenon. AB - In the present study, we investigated the release and permeation of hyaluronic acid (HA) encapsulated in liposomes when deposited onto two surfaces: cellulose, a model widely used for investigating transport of drugs; and human skin, a natural biointerface used for transdermal drug delivery. We prepared and characterised liposomes loaded with HA and liposomes incorporating two penetration enhancers (PEs): the non-ionic surfactant Tween 80, and Transcutol P, a solubilising agent able to mix with polar and non-polar solvents. In vitro and ex vivo permeation assays showed that PEs indeed enhance HA-release from liposomes. Since one of the possible mechanisms postulated for the action of liposomes on skin is related to its adsorption onto the stratum corneum (SC), we used atomic force microscopy (AFM) topography and force volume (FV) analysis to investigate the structures formed after deposition of liposome formulations onto the investigated surfaces. We explored the possible relationship between the formation of planar lipid structures on the surfaces and the permeation of HA. PMID- 26142627 TI - Aptamer-functionalized hydrogel as effective anti-cancer drugs delivery agents. AB - An aptamer-functionalized hydrogel has been developed, which can be regulated by the AS1411 aptamer with the sol-gel conversion. Also the hydrogel can be further utilized for the controlled encapsulation and release of the cancer drugs. Specially, the AS1411 initiates the hybridization of acrydite-modified oligonucleotides to form the hydrogels and the presence of the target protein nucleolin leads the gel to dissolve as a result of reducing the cross-linking density by competitive target-aptamer binding. Based on the rheology of hydrogels, it is possible to utilize this material for storing and releasing molecules. In this research, the cancer drug doxorubicin is encapsulated inside the gel during the formation of the hydrogel and then released in the presence of nucleolin. Further experiments are carried out to prove the specific recognition of target matter. In vitro researches confirm that the aptamer-functionalized hydrogels can be used as drug carriers in targeted therapy and other biotechnological applications. PMID- 26142628 TI - Galactose engineered solid lipid nanoparticles for targeted delivery of doxorubicin. AB - The present investigation reports the preparation, optimization, and characterization of surface engineered solid lipid nanoparticles (SLNs) encapsulated with doxorubicin (DOX). Salient features such as biocompatibility, controlled release, target competency, potential of penetration, improved physical stability, low cost and ease of scaling-up make SLNs viable alternative to liposomes for effective drug delivery. Galactosylation of SLNs instructs some gratifying characteristic, which leads to the evolution of promising delivery vehicles. The impendence of lectin receptors on different cell surfaces makes the galactosylated carriers admirable for targeted delivery of drugs to ameliorate their therapeutic index. Active participation of some lectin receptors in immune responses to antigen overlaid the application of galactosylated carriers in delivery of antigen and immunotherapy for treatment of maladies like cancer. These advantages revealed the promising potential of galactosylated carriers in each perspective of drug delivery. The developed DOX loaded galactosylated SLNs formulation was found to have particle size 239 +/- 2.40 nm, PDI 0.307 +/- 0.004, entrapment efficiency 72.3 +/- 0.9%. Higher cellular uptake, cytotoxicity, and nuclear localization of galactosylated SLNs against A549 cells revealed higher efficiency of the formulation. In a nutshell, the galactosylation strategy with SLNs could be a promising approach in improving the delivery of DOX for cancer therapy. PMID- 26142629 TI - Selective encapsulation of cesium ions using the cyclic peptide moiety of surfactin: Highly efficient removal based on an aqueous giant micellar system. AB - Cyclic peptide of surfactin (SF) is one of the promising environment-friendly biosurfactants abundantly produced by microorganisms such as Bacillus subtilis. SF is also known to act as an ionophore, wherein alkali metal ions can be trapped in the cyclic peptide. Especially, SF is expected to show high affinity for Cs(+) because of the distinctive cavity size and coordination number. In this study, we reported the specific interaction between SF and Cs(+) and succeeded in the highly efficient removal of Cs(+) from water using giant SF micelles as a natural sorbent. The specific interaction between SF and Cs(+) to form their inclusion complex was revealed by nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy. We found that SF micelles selectively encapsulate Cs(+), which was suggested by matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOFMS). A highly effective separation of Cs(+) immobilized on the surface of the SF micelles was also achieved through facile centrifugal ultrafiltration in 91% even in coexisting with other alkali metal ions such as Na(+) and K(+). Thus, the use of the giant micellar system of SF with its high Cs(+) affinity and distinctive assembling properties would be a new approach for the treatment of contaminated soil and water. PMID- 26142630 TI - Probing the position of resveratrol in lipid bilayers: A neutron reflectivity study. AB - The effect of the natural antioxidant resveratrol on the structure of solid supported di-palmitoyl-phosphatidyl-choline (DPPC) bilayers in their fluid state was investigated by neutron reflectometry. Results reveal an accumulation of resveratrol (up to 25%, mol/mol) inside the headgroups and they exclude its presence in the hydrophobic core. The presence of resveratrol induces an increase of the average thickness and of the interfacial roughness of the headgroup layer. This may be due to a change of the tilt angle of the phosphocholine headgroups residing next to the resveratrol to a more upright orientation and leading to a reduction of the projected area per headgroup. This effect is propagated into the hydrophobic core, where the chain packing is modified despite the absence of resveratrol. When interacting with a DPPC/cholesterol membrane, resveratrol has a similar effect on the neighboring PC headgroups as in the cholesterol free membrane. The almost precise 1:1 insertion ratio (resveratrol:cholesterol) suggests that resveratrol is most probably inserted on top of the hydroxyl group of the cholesterol in between the PC headgroups. The ordering effect of cholesterol on the hydrophobic core is absent when both cholesterol and resveratrol are present. Most probably, the interaction of resveratrol with lipid membranes is non-specific. PMID- 26142631 TI - The influence of gender on inheritance of exceptional longevity. AB - While the search for genetic contributors to exceptional longevity has yielded candidates, gender differences in inheritance have generally not been considered. The aim of this study was to investigate gender specific differences in the inheritance of exceptional longevity. Using a standardized questionnaire, we assessed the parental ages of death of Ashkenazi Jews with exceptional longevity and their spouses without exceptional longevity, who served as controls (n=1,114). Mothers of centenarian males and females had significantly longer lifespans compared to the mothers of non-centenarians, 79.0 +/- 13.4 vs. 73.0 +/- 16.3 years, p <0.01 and 75.7 +/- 15.8 vs. 70.5 +/- 18.0 years, p=0.02, respectively. There was also a trend toward longer lifespan among the fathers of centenarian men compared to the lifespan of fathers of non-centenarian men, 73.5 +/- 17.0 vs. 69.5 +/-15.0 years, p=0.07. The lifespan did not differ between the fathers of centenarian and non-centenarian daughters. Logistic regression models revealed that the odds of being a centenarian for the female and male offspring increased by 21% and 31%, respectively, for every additional 10 years of life achieved by the mother (p <0.05). These findings support a gender-specific inheritance pattern of human longevity and may help focus the search for longevity genes. PMID- 26142632 TI - Apelin attenuates the osteoblastic differentiation of aortic valve interstitial cells via the ERK and PI3-K/Akt pathways. AB - Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway. PMID- 26142634 TI - Heart Failure Prevention and Team-based Interventions. AB - There is substantial opportunity to reduce health care costs through prevention of heart failure. Team-based management of medical homes and large populations will be important for the success of any prevention interventions. Clinical trials of treatment are needed to show that heart failure is reduced by treatment. A team-based approach to treatment of asymptomatic left ventricular systolic dysfunction (LVSD) can work well with the availability of electronic medical records and a population approach to health. Attention should be given to optimizing risk factor reduction and preventive treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers if LVSD is present. PMID- 26142633 TI - High urinary homoarginine excretion is associated with low rates of all-cause mortality and graft failure in renal transplant recipients. AB - Renal transplant recipients (RTR) have an increased cardiovascular risk profile. Low levels of circulating homoarginine (hArg) are a novel risk factor for mortality and the progression of atherosclerosis. The kidney is known as a major source of hArg, suggesting that urinary excretion of hArg (UhArg) might be associated with mortality and graft failure in RTR. hArg was quantified by mass spectrometry in 24-h urine samples of 704 RTR (functioning graft >=1 year) and 103 healthy subjects. UhArg determinants were identified with multivariable linear regression models. Associations of UhArg with all-cause mortality and graft failure were assessed using multivariable Cox regression analyses. UhArg excretion was significantly lower in RTR compared to healthy controls [1.62 (1.09 2.61) vs. 2.46 (1.65-4.06) umol/24 h, P < 0.001]. In multivariable linear regression models, body surface area, diastolic blood pressure, eGFR, pre-emptive transplantation, serum albumin, albuminuria, urinary excretion of urea and uric acid and use of sirolimus were positively associated with UhArg, while donor age and serum phosphate were inversely associated (model R (2) = 0.43). During follow up for 3.1 (2.7-3.9) years, 83 (12 %) patients died and 45 (7 %) developed graft failure. UhArg was inversely associated with all-cause mortality [hazard risk (HR) 0.52 (95 % CI 0.40-0.66), P < 0.001] and graft failure [HR 0.58 (0.42-0.81), P = 0.001]. These associations remained independent of potential confounders. High UhArg levels are associated with reduced all-cause mortality and graft failure in RTR. Kidney-derived hArg is likely to be of particular importance for proper maintenance of cardiovascular and renal systems. PMID- 26142635 TI - Team-based Care for Patients Hospitalized with Heart Failure. AB - Hospitalizations for acute heart failure (HF) and subsequent readmissions have received increased attention because of the burden they place on patients, providers, and the health care system. These hospitalizations represent a significant portion of the total cost of HF care and health care in general. Although much of the care of the patient with HF occurs outside of the hospital, the genesis of the programs that attempt to limit repeat hospitalizations begin in the impatient setting. By using evidence-based guidelines, interdisciplinary teams, and comprehensive discharge planning, costly readmissions can be reduced and outcomes improved. PMID- 26142636 TI - Team-Based Transitions of Care in Heart Failure. AB - With the implementation of the Patient Protection and Affordable Care Act, the requisite for health care systems to build team-based transitional care programs is clear. The clinical course for patients with HF is complicated and progressive, which leads to frequent acute care hospitalization and higher mortality. These patients uniquely benefit from transitions of care programs that encourage a coordinated, multidisciplinary teambased approach to care. Evidence of the benefit of this approach to care is mounting. Research and advocacy efforts need to continue to facilitate the team-based approach to transitions and improve the quality of care. PMID- 26142637 TI - Team-Based Care for Outpatients with Heart Failure. AB - Management of heart failure requires a multidisciplinary team-based approach that includes coordination of numerous team members to ensure guideline-directed optimization of medical therapy, frequent and regular assessment of volume status, frequent education, use of cardiac rehabilitation, continued assessment for the use of advanced therapies, and advance care planning. All of these are important aspects of the management of this complex condition. PMID- 26142638 TI - Team-Based Care for Managing Cardiac Comorbidities in Heart Failure. AB - The need for HF management is predicted to increase as the HF population ages. Balancing HF and the multiple cardiac comorbidities remains difficult for any single provider, but becomes Fig. 6. Five-year rates of death or urgent heart transplantation by deciles of total cholesterol in heart failure. (From Horwich TB, Fonarow GC, Hamilton MA, et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002;8(4):222; with permission.) easier with the involvement of a team. Collaboration between physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other health care workers reduces the burden of care coordination and simultaneously improves delivery of care. Team-based approaches increase cost-effectiveness, reduce hospitalization rates, and equally important, give patients more resources and support, which research shows may ultimately improve compliance and outcomes. PMID- 26142639 TI - Team-Based Care for Managing Noncardiac Conditions in Patients with Heart Failure. AB - HF is a condition in which the prognosis and treatment are often defined by comorbidities, many of which are noncardiac. Knowledge of the interactions between HF and specific comorbidities is essential, yet to date the clinical trial evidence base for managing comorbidity in patients with HF is limited; further investigations are clearly needed. Perhaps the most pressing need is a focus on the overall multimorbidity state and its relationship to HF-a need that should be addressed in forthcoming trials. Successful navigation between HF and common interacting comorbidities requires coordination of care and team-based approaches that continually evolve to meet patient needs. PMID- 26142640 TI - Team-based Care for Cardiac Rehabilitation and Exercise Training in Heart Failure. AB - The estimated cost of treating patients with HF in the United States is expected to more than double by 2030.65 This forecast of the impact of HF in the United States should serve as a call to action. Despite well-documented benefits, participation in exercise training and CR programs by patients with HF remains low. In this article, standards and guidelines for exercise and CR in HF were reviewed. Although traditional CR had core components, it lacked care management specific for HF. Chronic stable HF patients can safely exercise; however, there are many unique needs that are not currently addressed at the patient, system, and provider levels. As we face economic and political forces that are expected to require major change to the health care delivery system, it becomes even more important to capitalize on the advantages that come with team-based care. CR has always served as a model of team-based care; however, the model must now include professionals with HF expertise to guide patients in safe exercise and self management strategies appropriate for this chronically ill population. PMID- 26142641 TI - Team-Based Care for External Telemonitoring in Patients with Heart Failure. AB - Multiple studies have been conducted assessing strategies for managing heart failure with the goal of decreasing admissions and readmissions, decreasing mortality, increasing self-management, and improving quality of life. Telemonitoring has been explored as an intervention to support and monitor adherence to all aspects of the heart failure management plan, including medication and appointment adherence, diet, exercise, and self-care. This article addresses the findings of studies and provides recommendations for future consideration. The need to apply the right interventions, to the right patient, at the right time, based on self-efficacy and readiness to change is also addressed. PMID- 26142642 TI - Team-based Care for Advanced Heart Failure. AB - Advanced heart failure (AHF) is the late stage of the heart failure syndrome that is associated with significant morbidity, high mortality, and rising costs that pose a significant burden for the different health care systems in the United States and worldwide. Despite advances in pharmacologic and device therapy, patients with AHF frequently require complex therapies, such as continuous infusion with inotropic agents, mechanical circulatory support, and heart transplant. This article summarizes the team-based approach to care of patients with AHF and those supported by left ventricular assist devices. PMID- 26142643 TI - Team-based Palliative and End-of-life Care for Heart Failure. AB - Clinical practice guidelines endorse the use of palliative care in patients with symptomatic heart failure. Palliative care is conceptualized as supportive care afforded to most patients with chronic, life-limiting illness. However, the optimal content and delivery of palliative care interventions remains unknown and its integration into existing heart failure disease management continues to be a challenge. Therefore, this article comments on the current state of multidisciplinary care for such patients, explores evidence supporting a team based approach to palliative and end-of-life care for patients with heart failure, and identifies high-priority areas for research. PMID- 26142645 TI - Foreword. The Winning Team in Heart Failure: Dimensionality of Care Redesign. PMID- 26142644 TI - Assessing the Quality and Comparative Effectiveness of Team-Based Care for Heart Failure: Who, What, Where, When, and How. AB - Team-based or multidisciplinary care may be a potential way to positively impact outcomes for heart failure (HF) patients by improving clinical outcomes, managing patient symptoms, and reducing costs. The multidisciplinary team includes the HF cardiologist, HF nurses, clinical pharmacists, dieticians, exercise specialists, mental health providers, social workers, primary care providers, and additional subspecialty providers. The timing and setting of multidisciplinary care depends on the needs of the patient and the resources available. Multidisciplinary HF teams should be evaluated based on their ability to achieve goals, as well as their potential for sustainability over time. PMID- 26142646 TI - Preface. Team-based Care for Heart Failure. PMID- 26142647 TI - Increased GADD34 in oligodendrocytes in Alzheimer's disease. AB - Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Abeta) and abnormally phosphorylated tau which contribute to endoplasmic reticulum (ER) stress. Previous studies demonstrated that Abeta and a truncated fragment of Abeta induced death of oligodendrocytes in vitro. In addition, a triple-transgenic AD mouse model exhibits significant region-specific alterations in myelination patterns at time points preceding the appearance of Abeta accumulation. The growth arrest and DNA damage protein (GADD) 34 is up-regulated in response to ER stress and regulates subunit of protein phosphatase 1 (PP1) complex that dephosphorylates eukaryotic translation initiator factor 2alpha (elF2alpha). Thus, GADD34 is known as an ER stress regulator or ER stress marker. In a recent study, GADD34 was induced in the spinal cord glial cells of an amyotrophic lateral sclerosis (ALS) mouse model. It is interesting that reduced GADD34 delayed the onset of ALS and prolonged the survival period in the mouse model. In this study, we have demonstrated that GADD34 was increased in neurons of human AD brains. Additionally, this finding was also observed in oligodendrocytes in human AD brains. Furthermore, we showed that the expression levels of GADD34 in neurons and oligodendrocytes were significantly increased in the early stage of AD in the mouse model. As oligodendrocytes were more affected in the early stages of AD in this experimental model, ER stress of Abeta oligomers may be more related to oligodendrocytes than to neurons. These results suggest that GADD34 could be a therapeutic target for preventing ER stress in neuronal cells in AD. PMID- 26142648 TI - Recommendations for post-adaption care of an ocular prosthesis: A review. AB - An ocular prosthesis must be maintained in a suitable state of cleanliness, fit and preservation. Otherwise its functioning may be compromised, leading to a variety of diseases. However, there is a lack of consensus on the care of such prostheses. This review assembles and attempts to update existing knowledge in this area and discusses the most appropriate care regimes. PMID- 26142649 TI - Cardiovascular risk factors in severely obese adolescents. PMID- 26142650 TI - Mismatch negativity in children with specific language impairment and auditory processing disorder. AB - INTRODUCTION: Mismatch negativity, an electrophysiological measure, evaluates the brain's capacity to discriminate sounds, regardless of attentional and behavioral capacity. Thus, this auditory event-related potential is promising in the study of the neurophysiological basis underlying auditory processing. OBJECTIVE: To investigate complex acoustic signals (speech) encoded in the auditory nervous system of children with specific language impairment and compare with children with auditory processing disorders and typical development through the mismatch negativity paradigm. METHODS: It was a prospective study. 75 children (6-12 years) participated in this study: 25 children with specific language impairment, 25 with auditory processing disorders, and 25 with typical development. Mismatch negativity was obtained by subtracting from the waves obtained by the stimuli /ga/ (frequent) and /da/ (rare). Measures of mismatch negativity latency and two amplitude measures were analyzed. RESULTS: It was possible to verify an absence of mismatch negativity in 16% children with specific language impairment and 24% children with auditory processing disorders. In the comparative analysis, auditory processing disorders and specific language impairment showed higher latency values and lower amplitude values compared to typical development. CONCLUSION: These data demonstrate changes in the automatic discrimination of crucial acoustic components of speech sounds in children with specific language impairment and auditory processing disorders. It could indicate problems in physiological processes responsible for ensuring the discrimination of acoustic contrasts in pre-attentional and pre-conscious levels, contributing to poor perception. PMID- 26142651 TI - Drug-induced sleep endoscopy in the identification of obstruction sites in patients with obstructive sleep apnea: a systematic review. AB - INTRODUCTION: Obstructive sleep apnea syndrome has multifactorial causes. Although indications for surgery are evaluated by well-known diagnostic tests in the awake state, these do not always correlate with satisfactory surgical results. OBJECTIVE: To undertake a systematic review on endoscopy during sleep, as one element of the diagnosis routine, aiming to identify upper airway obstruction sites in adult patients with OSAS. METHODS: By means of electronic databases, a systematic review was performed of studies using drug-induced sleep endoscopy to identify obstruction sites in patients with OSAS. RESULTS: Ten articles were selected that demonstrated the importance of identifying multilevel obstruction, especially in relation to retrolingual and laryngeal collapse in OSAS. CONCLUSION: DISE is an additional method to reveal obstruction sites that have not been detected in awake patients. PMID- 26142653 TI - Personalizing pelvic floor reconstructive surgery in aging women. AB - Pelvic floor dysfunction is a growingly frequent condition in aging individuals. Urinary or rectal incontinence, constipation, pelvic organ prolapse, pelvic pain or sexual dysfunction are common problems in this age range. Such conditions carry a severe impact on quality of life, but also limit individual independence in daily activities, favor social isolation and carry health risks. Diagnosis and treatment of pelvic floor dysfunction in aging women is tricky, since multiple interfering conditions affecting muscle tone and nerve function are common in these individuals. Diabetes mellitus, sarcopenia, use of drugs that affect cognition or impact bowel or urinary function are just a few examples. These conditions need to be thoroughly taken into account during pre-operative work up for their potential impact on the success of surgery and vice versa. Functional reconstruction aimed at treating symptoms rather than anatomic defects is key to success. The recent advancements in surgical treatment of urinary incontinence and pelvic organ prolapse allow for more options to achieve the best surgery in each patient. PMID- 26142652 TI - Pharmacological Modulation of the Mitochondrial Electron Transport Chain in Paclitaxel-Induced Painful Peripheral Neuropathy. AB - Paclitaxel is an effective first-line chemotherapeutic with the major dose limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. PERSPECTIVE: This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive effects in a preclinical model of paclitaxel-induced pain. PMID- 26142654 TI - Determinants in treatment decision-making in older patients with symptomatic severe aortic stenosis. AB - BACKGROUND: Three treatment options are available for patients with aortic stenosis: surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI) and medical treatment (MT). However, little is known about how Heart Team treatment decisions are made under routine conditions. The aim of this study was to identify the cardiac and geriatric components associated with treatment decision-making in older patients with symptomatic severe aortic stenosis. METHODS: Between 2011 and 2013, 337 consecutive patients >=75 years old referred for pre-operative evaluation in Nantes University Hospital had a comprehensive cardiac and geriatric assessment. In this observational retrospective study, relationships between treatment decision-making and cardiac or geriatric components were evaluated through multivariable models. RESULTS: Surgical aortic valve replacement was proposed to 108 patients, TAVI to 131 and medical treatment to 98 patients. Mean age was 83+/-4 years and 51% were women. Geriatric components associated with treatment decision-making between SAVR vs. TAVI were age (p<0.001, OR=0.790), comorbidity score (p=0.027, OR=0.86), functional status (p<0.001, OR=1.46), and gait speed (p<0.001, OR=0.23). Cardiac components associated with decision-making between SAVR vs. TAVI were history of previous cardiac surgery (p<0.001, OR=0.09), left ventricular ejection fraction <50% (p<0.001, OR=0.14), coronary artery disease requiring revascularization (p=0.019, OR=0.4). Between TAVI vs. medical treatment, only history of previous cardiac surgery and presence of another severe valve disease were significant. CONCLUSION: Comorbidities, functional status and physical performance, were significantly associated with the consensual treatment decision-making, independently of cardiac components in older patients with symptomatic severe aortic stenosis. PMID- 26142655 TI - PC-ANN assisted to the determination of Vanadium (IV) ion using an optical sensor based on immobilization of Eriochorome Cyanine R on a triacetylcellulose film. AB - More detailed analytical studies of an optical sensor based on immobilization of Eriochorome Cyanine R (ECR) on a triacetylcellulose film have been described to determine Vanadium (IV) ions in some real samples. The sensor based on complex formation between Vanadium (IV) ions and ECR in acidic media caused the color of the film to change from violet to blue along with the appearance of a strong peak appears at 595 nm. At the optimal conditions, the calibration curve showed a linear range of 9.90*10(-7)-8.25*10(-5)mol L(-1). Vanadium (IV) ions can be detected with a detection limit of 1.03*10(-7)mol L(-1) within 15 min depending on its concentration. Also, the working range was improved by using PC-ANN algorithm. The sensor could regenerate with dilute acetic acid solution and could be completely reversible. The proposed sensor was successfully applied for determining V (IV) ions in environmental water and tea leaves. PMID- 26142656 TI - Comment on "Density functional theory studies on molecular structure, vibrational spectra and electronic properties of cyanuric acid". AB - In a recently published paper [Spectrochim. Acta A: Mol. Biomol. Spect. 138 (2015) 711-722], Prabhaharan, Prabakaran, Srinivasan, and Gunasekaran presented a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of cyanuric acid, and explain their findings using the tri-hydroxy tautomeric form of the compound. In reality, the compound adopts the tri-oxo tautomeric form, which is by over 100kJmol(-1) more stable comparatively to the tri-hydroxy tautomer discussed and characterized by Prabhaharan et al. PMID- 26142657 TI - Spectroscopic study on interaction between three cationic surfactants with different alkyl chain lengths and DNA. AB - In this study, the interaction between cationic surfactants with different alkyl chain lengths, such as hexyltrimethyl ammonium bromide (HTAB), dodecyltrimethyl ammonium bromide (DTAB) and cetyltrimethyl ammonium bromide (CTAB), and DNA was investigated by UV-vis spectroscopy, fluorescence spectroscopy and viscosity techniques. The results showed that these three cationic surfactants with different hydrocarbon chain lengths could all interact with DNA. Their binding modes were estimated and their interaction strength was compared. In addition, the effects of the surfactant, NaCl and phosphate ion concentrations on the interaction were reviewed. It is wished that this work would provide some valuable references to investigate the influence of cationic surfactants with different alkyl chain lengths on DNA. PMID- 26142658 TI - Structure and spectroscopic characterization of tetrathia- and tetraselena[8]circulenes as a new class of polyaromatic heterocycles. AB - The FTIR, Raman and UV-vis spectra of the recently synthesized tetrathia[8]circulene and tetraselena[8]circulene compounds have been measured and interpreted in details by the density functional theory (DFT) calculations taking into account the molecular symmetry constrains. The structural and electronic features of the studied compounds have also been discussed in connection with the observed spectroscopic characteristics. Particularly, we have found that despite a slightly non-planar conformation the neutral tetrathia[8]circulene and tetraselena[8]circulene molecules demonstrate bifacial aromatic/antiaromatic nature. The inner octatetraene core is characterized by the presence of paratropic ("antiaromatic") ring currents, whereas the outer macrocycle constructed of benzene, thiophene or selenophene rings possesses the strong magnetically-induced diatropic ("aromatic") ring current. This fact suggests the general electronic and magnetic similarity of the tetrathia- and tetraselena[8]circulenes with the strictly planar isoelectronic tetraoxa[8]circulene and related azaoxa-derivatives discussed earlier. However, the vibrational and UV-vis absorption spectra of the studied circulenes are rather different from those of the parent tetraoxa[8]circulene which indicates a clear manifestation of the symmetry selection rules. PMID- 26142659 TI - Femtosecond coherent anti-Stokes Raman scattering spectroscopy of hydrogen bonded structure in water and aqueous solutions. AB - Femtosecond coherent anti-Stokes Raman scattering (fsCARS) spectroscopy, together with perturbation theory based numerical calculation, is employed to study OH stretching (upsilonOH) of pure water and aqueous lithium chloride solutions. Vibrational OH stretching (upsilonOH) modes of aqueous solutions are Raman excited by a pair of ultrashort, femtosecond laser pulses, and then probed through inelastic scattering of a third, time-delayed laser field. In order to overcome limited spectral resolution of fsCARS, numerical evaluation of the CARS signal through vibrational wave packet propagation was employed in order to confirm the position of distinctive OH stretching mode that is complicated by intramolecular and intermolecular vibrational coupling. Moreover, in order to come to a microscopic description of the observed CARS spectra for aqueous solutions, we have performed molecular dynamics simulations of aqueous lithium chloride solutions with varying concentrations at ambient conditions. To this end we have analyzed the equilibrium distributions of hydrogen bonds in the first solvation shells of the ions as well as in bulk water and also computed the average number of hydrogen bonds per water molecule. According to our experimental and theoretical results on time evolution of Raman OH stretching band of water, it can be inferred that the dissolved ions mainly influence hydrogen bond strength and structure of water molecules in the first hydration shell, the addition of lithium chloride primarily breaks the tetrahedral hydrogen bonding, promotes formation of the donor hydrogen bonding in water, and slightly increases the amount of free OH bonds. PMID- 26142660 TI - Dedicated to Professor Piero Cappuccinelli: the man for cooperation with developing countries. PMID- 26142661 TI - Lessons to learn from MERS-CoV outbreak in South Korea. AB - Since the first identification of Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) in 2012 the virus has infected 1289 humans with approximately 40% mortalities. Currently South Korea is experiencing the hospital-associated outbreak of MER-CoV that has infected 126 human cases and 13 deaths, as of 12 June 2015, following the return of a MERS infected patient from Middle East. The episode is characterized unique being the largest cluster of patients linked to the single introduction of virus that involves three generations of virus transmission. Human-to-human transmission though was observed on several occasions in past, it is documented as non-sustainable event. The recent outbreak including the healthcare workers, index case's roommates and their caregivers, raises several concerns about the infection control practices and timely diagnosis of MERS. PMID- 26142662 TI - An overview of Staphylococcus epidermidis and Staphylococcus aureus with a focus on developing countries. AB - Most nosocomial infections by Staphylococcus epidermidis and Staphylococcus aureus have gained considerable attention due to an increase of infections caused by these strains that have been reported in recent years throughout the world. Most notably, it is important to underline the presence of S. epidermidis and S. aureus in the human epithelia microflora and to highlight that it is impossible to eradicate them from humans. There are various virulence factors that normally sustain the infection life cycle, such as antibiotic resistance (methicillin resistance). Furthermore, it is important to evaluate the usefulness of typing the spa gene from isolated strains in order to study genotypes and geographical distributions. In the present review, different cases related to patients infected by Staphylococci and an overview of this problem worldwide are reported. PMID- 26142663 TI - Diagnosis of viral gastroenteritis: limits and potential of currently available procedures. AB - The diagnostic approaches to viral gastroenteritis have evolved substantially over the past decades because of the advances in detection methods, the emergence of new pathogens, and the increase in diarrhea hospitalizations attributed to viruses, especially in young children in non-industrialized countries. Overall, these factors have lead to a relevant improvement of types and operating characteristics of diagnostic methods (including sensitivity and specificity), as well as turnaround time. In this review, clinical and laboratory approaches to the diagnosis of viruses causing gastroenteritis are presented; in particular, specimen collection and detection methods are reviewed and discussed, taking into account performance and limitations. PMID- 26142664 TI - Global impact of Torque teno virus infection in wild and domesticated animals. AB - Infection with Torque teno viruses (TTVs) is not restricted to humans. Different domestic and wild animal species are naturally infected with species-specific TTVs worldwide. Due to the global spread of the infection, it is likely that essentially all animals are naturally infected with species-specific TTVs, and that co-evolution of TTVs with their hosts probably occurred. Although TTVs are potentially related to many diseases, the evidence of the widespread infection in healthy human and nonhuman hosts raised doubts about their pathogenic potential. Nonetheless, their role as superimposed agents of other diseases or as triggers for impairment of immune surveillance is currently under debate. The possible contribution of animal TT viruses to interspecies transmission and their role as zoonotic agents are currently topics of discussion. PMID- 26142665 TI - Current studies on human papillomavirus in Saudi Arabia. AB - Human papillomavirus (HPV) infection is a significant etiological factor and an important prognosticator in cervical cancer. Indeed, researchers worldwide have confirmed these roles for high-risk HVPs in over 70% of cervical cancer cases. According to the World Health Organization, approximately 561,200 new cancer cases (5.2% of all new cancers) are attributed to HPV infection. Over 120 types of HPV are classified further as either low-risk HPV (LR-HPV) or high-risk HPV (HR-HPV) based on their oncological potential of transforming cells. The LR-HPV types cause benign hyperproliferative lesions (i.e. genital warts) while the HR HPV types are strongly associated with premalignant and malignant cervical lesions. Data on the prevalence of HPV, survival of infected patients, and mortality rate are scarce in Saudi Arabia. The unsubstantiated assumption of a low prevalence of HPV in Saudi Arabia has contributed to limiting HPV research in this conservative country. Therefore, the goal of this review is to shed light on the current HPV research being conducted and the prevalence of HPV in Saudi Arabia. PMID- 26142666 TI - The aliens inside human DNA: HERV-W/MSRV/syncytin-1 endogenous retroviruses and neurodegeneration. AB - The human genome contains remnants of ancestral retroviruses now endogenously transmitted, called human endogenous retroviruses (HERVs). HERVs can be variably expressed, and both beneficial and detrimental effects have described. This review focuses on the MSRV and syncytin-1 HERV-W elements in relationship to neurodegeneration in view of their neuro-pathogenic and immune-pathogenic properties. Multiple sclerosis (MS) and a neurodegenerative disease (neuroAIDS) are reported in this review. In vivo studies in patients and controls for molecular epidemiology and follow-up studies are reviewed, along with in vitro cellular studies of the effects of treatments and of molecular mechanisms. HERV W/MSRV has been repeatedly found in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly parallels MS stages and active/remission phases, as well as therapy outcome. The DNA of MS patients has increased MSRVenv copies, while syncytin-1 copies are unchanged in controls. Presence of MSRV in the spinal fluid predicted the worst MS progression, ten years in advance. The Epstein-Barr virus (EBV) activates HERV-W/MSRV both in vitro and in vivo. With respect to neuroAIDS, the HIV transactivator of transcription (Tat) protein activates HERV-W/MSRV in monocytes/macrophages and astrocytes indirectly by interaction with TLR4 and induction of TNFa. HERV-W/MSRV can be considered a biomarker for MS behavior and therapy outcome. Regarding MS pathogenesis, we postulate the possibility for EBV of an initial trigger of future MS, years later, and for MSRV of a direct role of effector of neuropathogenesis during MS. Additionally, HERV-W/MSR/syncytin-1 activation by HIV Tat could contribute to the HIV-related neurodegeneration. PMID- 26142667 TI - Recent updates and perspectives on leishmaniasis. AB - Leishmaniasis is a neglected vector-borne tropical infection considered to be a disease of the poor. Concentrated in poverty-stricken countries within Southeast Asia, East Africa, and Latin America, it is also endemic in several Mediterranean countries. The management of the heterogeneous syndromes determined by parasites belonging to the genus Leishmania is particularly difficult in developed, non endemic countries owing to the unfamiliarity of physicians with clinical symptoms, diagnostic possibilities, and available treatment options. Therefore, travelers and other people who may be exposed to sand flies in endemic areas should receive counseling regarding leishmaniasis and appropriate protective measures. Serological diagnosis is rarely used for cutaneous and mucocutaneous diseases, but it is the most commonly used technique for visceral leishmaniasis. The drugs used to treat this last disease are expensive and sometimes have toxic side effects. This review highlights the diagnostic, chemotherapeutic, and immunizing strategies to control leishmaniasis, though no human vaccine is commercially available currently owing to the complexity of the cellular immune response to this parasite. PMID- 26142668 TI - Artemisinin resistance, some facts and opinions. AB - Resistance to artemisinin derivatives (ARTs) in malaria disease is currently defined as a delayed parasite clearance following artemisinin combined therapy (ACT). Although ACT is still widely effective, the first evidence of artemisinin resistance was described in 2009 in Southeast Asia. Since then, resistance to ARTs / ACT has been monitored showing an increasing trend. The demonstrated resistance to all drugs that are currently associated to ART, the ambiguous finding that ART resistance is observed only in presence of resistance to the partner drug, the lack of a mechanistic rationale to choose the partner drugs and the lack of markers with known specificity and sensitivity to monitor ART resistance, represent the most worrisome issues. PMID- 26142669 TI - Vaccines for tumor prevention: a pipe dream? AB - Whether or not a tumor expresses peculiar antigens that differentiate it from normal cells was intensively investigated in the 1950s. A conclusive answer was provided in 1960 when George Klein showed that a tumor can be rejected by the immune response elicited by a vaccine administered to the same mouse in which the tumor was induced. Whether immunogenicity was a feature restricted only to tumors artificially induced by viruses or by high doses of chemical carcinogens was then hotly debated until Terry Boon showed, in the 1980s, that almost any tumor can be recognized by a syngeneic immune system triggered by an appropriate cancer vaccine. However, the therapeutic efficacy of vaccine-induced immunity against an advanced tumor is marginal. The combination of an anti-tumor vaccine with new sophisticated maneuvers to contrast tumor-induced suppression may yield new and effective therapeutic strategies. Also, the exploitation of tumor vaccines to prevent tumors in cohorts of people with a specific risk of cancer may become a fresh strategy with great potential to control tumor onset. PMID- 26142670 TI - Antimicrobial resistance in Helicobacter pylori: current situation and management strategy in Vietnam. AB - Increasing antimicrobial resistance to key antibiotics in Helicobacter pylori has become a main cause of treatment failures in many countries, including Vietnam. For this reason it is advisable to perform antimicrobial sensitivity tests to provide more focused regimens for H. pylori eradication. However, this approach is generally unavailable for H. pylori in Vietnam and the selection of treatment regimens is mainly based on the trend of antibiotic use in the population, resistance development in the region, and history of H. pylori eradication of patients. The aim of this review is to examine the current situation of antimicrobial resistance in Vietnam and suggest management strategies for treatment selection. PMID- 26142671 TI - Susceptibility of autoimmune diseases in three polymorphisms of infection associated gene IRAK1. AB - INTRODUCTION: Infection of pathogenic microorganisms is an important reason for autoimmune diseases (ADs). Interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK1) is a key mediator in infection immunity, while the gene of IRAK1 is recognized as a risk gene in ADs. Three single nucleotide polymorphisms (SNPs) in IRAK1 (rs3027898, rs1059702, rs1059703) are considered to be associated with ADs risk. However, the results are conflicting. We conducted this study to get more precise estimations. METHODOLOGY: PubMed, OvidSP, and CNKI databases (published prior to August 2014) were searched, and data was extracted from eligible studies. The procedure of statistical analysis was performed using STATA 12.0 software. A random effect model or fixed effect model was chosen based on the between-study heterogeneities. RESULTS: Of the studies involved, 11 studies included 10,705 cases (9,865 controls) for rs3027898, 9 studies included 15,005 cases (14,997 controls) for rs1059702, and 7 studies included 8,115 cases (6,815 controls) for rs1059703. Overall, the results showed that there were significant associations with ADs risk in three genetic models for rs3027898 and in four genetic models for rs1059702, but in neither model for rs1059703. Moreover, in stratified analyses, different extents of associations were found in some different genetic models for all three SNPs. CONCLUSION: Our data demonstrated that these three SNPs (rs3027898, rs1059702, rs1059703) in IRAK1 were associated with ADs risk. PMID- 26142672 TI - Molecular diagnostics and ITS-based phylogenic analysis of Streptococcus suis serotype 2 in central Vietnam. AB - INTRODUCTION: Streptococcus suis (S. suis) serotype 2 has recently become the most prevalent cause of meningitis in adults in many areas of Vietnam. This study provides data on S. suis molecular diagnosis in central Vietnam using a real-time polymerase chain reaction (PCR) assay targeting the S. suis serotype 2 cps2J gene. Additionally, 16S-23S rDNA intragenic spacer (ITS)-based phylogenic analysis of strains isolated from cerebrospinal fluid (CSF) in Thua Thien Hue Province, Vietnam, is presented and discussed. METHODOLOGY: Pathogenic bacteria were isolated from 40 CSF samples, and 18 were identified as S. suis by culture dependent methods. Capsular serotyping was assessed by real-time PCR. ITS sequences were obtained after traditional PCR and were used in phylogenic analyses. RESULTS: Pathogenic bacteria were isolated from 36 out of 40 CSF samples. A total of 18 S. suis strains were isolated and assigned to serotype 2 by real-time PCR. One CSF sample, negative when tested by culture-dependent methods, was positive to S. suis serotype 2 by real-time PCR. Pairwise alignments of the 18 ITS sequences did not reveal any variable nucleotide position, and resulted in a single sequence type. Sequences were similar to S. suis serotype 2 reference ITS sequences (> 98.1%), and there was no lack of an ITS spacer region in the isolates. CONCLUSIONS: S. suis serotype 2 is the most prevalent serotype in central Vietnam. Real-time PCR assay proved to be a reliable diagnostic method for early detection of S. suis 2 in CSF samples. PMID- 26142673 TI - Lack of humoral response against Helicobacter pylori peptides homologous to human ZnT8 in Hashimoto's thyroiditis patients. AB - INTRODUCTION: The Helicobacter pylori (HP) reinfection rate seems to be higher in developing countries than in developed ones. An increased seroprevalence of HP has also been reported in patients with type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT). Mycobacterium avium subsp. paratuberculosis (MAP) has been linked to both T1D and HT. Quite a few lines of evidence indicate that autoantibodies against several epitopes belonging to human zinc transporter 8 (ZnT8) cross-recognize the homologous MAP3865c epitopes in both T1D and HT patients. HP may play a role in HT disease, most likely acting through a molecular mimicry mechanism that targets ZnT8 as reported for MAP and the two autoimmune diseases. METHODOLOGY: An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of antibodies against several epitopes deriving from HP proteins, which are highly homologous to the immunodominant ZnT8 peptides previously identified: ZnT8178-186 and ZnT8186-194. RESULTS: None of the HP peptides tested were significantly recognized when the humoral responses of 92 HT patients and 91 healthy volunteers were analyzed. CONCLUSIONS: These findings do not support a triggering role for HP (through ZnT8 mimicking) in HT. If a molecular mimicry phenomenon is taking place, it involves a different self antigen. Moreover, the negative outcome of the experiments performed stresses the fact that sharing stretches of sequence homology is relevant, but not enough to trigger an antibody-mediated cross-recognition. PMID- 26142674 TI - Epidemic waves of cholera in the last two decades in Mozambique. AB - INTRODUCTION: Africa is increasingly affected by cholera. In Mozambique, cholera appeared in the early 1970s when the seventh pandemic entered Africa from the Indian subcontinent. In the following decades, several epidemics were registered in the country, the 1997-1999 epidemic being the most extended. Since then, Mozambique has been considered an endemic area for cholera, characterized by yearly outbreaks occurring with a seasonal pattern. At least three pandemic variants are thought to have originated in the Indian subcontinent and spread worldwide at different times. To understand the epidemiology of cholera in Mozambique, whether the disease re-emerges periodically or is imported by different routes of transmission, we investigated clinical V. cholerae O1 isolated during 1997-1999 and 2012-2014 epidemics. METHODOLOGY: By detecting and characterizing seven genetic elements, the mobilome profile of each isolate was obtained. By comparing it to known seventh pandemic reference strains, it was possible to discern among different V. cholerae O1 variants active in the country. RESULTS: During 1997-1999, epidemic strains showed two different genetic profiles, both related to a pandemic clone that originated from India and was reported in other African countries in the 1990s. Isolates from 2012-2014 outbreaks showed a genetic background related to the pandemic strains currently active as the prevalent causative agent of cholera worldwide. CONCLUSIONS: Despite cholera being endemic in Mozambique, the epidemiology of the disease in the past 20 years has been strongly influenced by the cholera seventh pandemic waves that originated in the Indian subcontinent. PMID- 26142675 TI - Immune response to Vi polysaccharide, heat-killed whole cells, and outer membrane protein of Salmonella typhi. AB - INTRODUCTION: Salmonella typhiVi capsular polysaccharide (ViCPS) is a licensed vaccine against typhoid fever in many countries; in Egypt, the killed whole-cell vaccine is still used. In this study, mice were used as an animal model to evaluate the immune response to ViCPS and other S. typhi antigens such as heat killed whole cells and outer membrane protein (OMP). METHODOLOGY: The three antigens were laboratory prepared, injected into mice groups, and the humoral response was evaluated using the indirect whole-cell enzyme-linked immunosorbent assay (ELISA). The sensitivity of this assay was investigated using in situ or pre-heated whole cells as coating antigens. In addition, the effect of the immunization route for ViCPS was examined. RESULTS: Immunizing doses of heat killed whole cells as well as ViCPS, 2 and 4 ug given subcutaneously (SC) and 4 ug given intraperitoneally (IP), showed significant immune response compared to controls. However, the responses to these doses were not significantly different from each other. The OMP showed a higher significant response. The sensitivity of indirect whole-cell ELISA was enhanced significantly by in situ heat treatment of the coating antigen rather than the pre-heated coating antigen. CONCLUSIONS: The three antigens showed significant immune response. The immune response to OMP was higher. Though heat-killed whole cells and ViCPS are almost similar in immunizing level, ViCPS is recommended. The SC route was more immunizing than the IP one. Furthermore, the sensitivity of the indirect whole-cell ELISA technique could be enhanced by in situ heat inactivation of the coating cells. PMID- 26142676 TI - Essential oils in ocular pathology: an experimental study. AB - INTRODUCTION: The antimicrobial activity of essential oils (EOs) has been known for ages; in particular, the EOs of Melaleuca alternifolia, Thymus vulgaris, Mentha piperita, and Rosmarinus officinalis have been used for the treatment of fungal and bacterial infections. METHODOLOGY: This study focused on the in vitro cytotoxicity to normal human conjunctiva cells and antimicrobial activity of 20 EOs. RESULTS: The oils tested showed no cytotoxic effect at very low concentrations. Rosmarinus officinalis, Melaleuca alternifolia, and Thymus vulgaris L. red thyme geraniol sel oils had good antimicrobial activity against Gram-positive and Gram-negative strains. CONCLUSIONS: The results of this study are of great interest and may have a major impact on public health, providing useful tips to optimize the therapeutic use of some natural drugs. PMID- 26142677 TI - Prevalence of Trichomonas vaginalis infection in symptomatic and asymptomatic women in Central Vietnam. AB - INTRODUCTION: The diffusion of trichomoniasis in Vietnam has been scarcely studied. The aim of this study was to investigate the prevalence of trichomoniasis in a group of symptomatic and asymptomatic women in Central Vietnam. Relationships between education, socioeconomical and marital status, and sexual behavior with infection have also been investigated. METHODOLOGY: 249 symptomatic and 534 asymptomatic women from Hue City, Vietnam, were enrolled in this study. All women were interviewed about socioeconomical and behavioral status. They underwent clinical examination, and vaginal swabs were taken to assess T. vaginalis infection by wet mount microscopy examination. In addition, an ELISA test to detect antibodies to T. vaginalis in patients' sera was used. RESULTS: The overall prevalence of trichomoniasis assessed by microscopic examination was 6.6%. A significant difference between symptomatic and asymptomatic groups was observed, resulting in 19.3% and 0.7%, respectively. Anti T. vaginalis antibodies were detected in 31.3% of symptomatic and in 13.3% of asymptomatic women. High-risk sexual behaviour, residence in urban areas, and low level of education were positively associated with infection. CONCLUSION: This is the first report on the diffusion of trichomoniasis in Central Vietnam on symptomatic and asymptomatic subjects. Data demonstrated that T. vaginalis is a common cause of vaginal infection in the Hue province. The prevalence detected by microscopic examination was high in symptomatic subjects, while serological ELISA test detected infection also in asymptomatic patients, who tested negative by microscopy. The ELISA test may be useful to detect infection, especially in asymptomatic population. PMID- 26142678 TI - Genetic determinants of pathogenicity of Escherichia coli isolated from children with acute diarrhea in Maputo, Mozambique. AB - INTRODUCTION: Diarrheagenic Escherichia coli (DEC) represents one of the leading cause of diarrhoea in developing countries. In this study a molecular approach was applied for the detection of diarrheagenic Escherichia coli (DEC) circulating in Maputo, Mozambique. METHODOLOGY: All isolates were PCR tested for species specific genes and for 11 molecular markers: stx1, stx2, eae, bfpA, lt, st, ipaH, aap, aggR CVD432 and daaE. RESULTS: Of the 80 E. coli isolated, 74% were potential DEC: 21% EIEC, 19% EPEC, 15% EAEC, 13% ETEC, 5% DAEC and 1% hybrids. CONCLISION: This study revealed the complexity of the etiology of diarrhea caused by pathogenic E. coli in Mozambique, and the risk of the emergence of new pathogenic variants due to the horizontal transmission of pathogenicity factors. PMID- 26142679 TI - Genetic relatedness of clinical and environmental Acinetobacter baumanii isolates from an intensive care unit outbreak. AB - INTRODUCTION: Determination of microbial genetic relatedness is important for improving efficiency of infection control measures during hospital outbreaks. This study aimed to analyze the clonal relationships of clinical and environmental Acinetobacter baumannii strains isolated during an outbreak in the intensive care unit (ICU) of a secondary care hospital in Saudi Arabia. METHODOLOGY: Twelve clinical and fourteen environmental A. baumannii isolates identified during an outbreak in February 2013 in the 14-bed adult intensive care unit of a tertiary care hospital in Riyadh, Saudi Arabia, were studied. Bacterial identification and antimicrobial susceptibility testing were carried out using Microscan Walkaway 96 automated system. Determination of clonal diversity was investigated by repetitive-sequence-based polymerase chain reaction (rep-PCR) with the semi-automated DiversiLab system. RESULTS: The majority of the clinical isolates were from endotracheal tube aspirates (n = 9), one from a wound swab and two were from urine and sputum, respectively. Environmental isolates were from bed railings (n = 10) and with one each from curtain, stethoscope, computer mouse and telephone. Isolates were categorized into 6 clusters (Groups 1-6). Most of the isolates were associated with two clusters namely Groups 2 (n = 11) and 3 (n = 9). All isolates were multidrug resistant showing resistance to three or more classes of antibiotics. One clinical strain from Cluster 3 was resistant to colistin (MIC > 4ug/ml). CONCLUSION: This outbreak was caused by two clonal groups of multidrug resistant A. baumannii. The presence of multiple environmental clones was suggestive of environmental source dissemination via healthcare workers within the ICU. PMID- 26142680 TI - Fasciolopsis buski infection in a Vietnamese pregnant woman with systemic lupus erythematosus. AB - A clinical case of infection caused by Fasciolopsis buski in a 24 weeks pregnant woman from Vietnam affected by systemic lupus erythematosus (SLE) is reported here. On 22 February 2012 the patient was admitted to Hue Hospital in Hue, Vietnam, with a diagnosis of general illness and suspected acute anaemia. Laboratory analysis indicated possible SLE syndrome and coprological tests demonstrated the presence of F. buski eggs. During hospitalization the patient naturally eliminated the adult form in faeces suggesting the infection had already progressed at least for three months. One month after hospitalization due to the high severity of both SLE and fasciolopsiasis, a medical abortion was carried out and the following day the patient died. Even though infection due to Fasciolopsis buski is rare, this case highlights the importance of an accurate and prompt diagnosis of this infectious agent, which may have saved the foetus and mother's lives. PMID- 26142681 TI - Helicobacter pylori: enemy, commensal or, sometimes, friend? AB - Helicobacter pylori is a Gram-negative epsilon-proteobacterium that colonizes about 50% of humans. Some pertinent characteristics are that it can survive the acid of the stomach, produces urease to neutralize it and is motile due to apical flagella. Not surprisingly given its wide distribution, it has long colonized mankind and its genome encodes many features that allows this. Consequently, it frequently has a persistent lifelong association with humans and, differently from most pathogens that are transmitted horizontally, it is preferentially transmitted vertically, often from mother to child. A variety of genes and polymorphisms, both in H pylori and in humans, mediate the complex host-bacterium relationship, and can also determine if and what pathologies will be triggered by the species. H. pylori is naturally transformable, very recombinogenic and has a high mutation rate. Microbiota studies of the stomach have shown it to be an important species with a potentially regulatory role for the gastric microbial community. Likewise, epidemiological work has suggested that, while it clearly increases the risk of peptic ulcers and gastric cancer in some populations, it is also associated with lower risk of esophageal cancer and several other important pathologies. More recently, antibacterial resistant strains have been isolated, posing a problem for public health officials who called for its eradication. Hence, study of H. pylori and how it interacts with us can help revealing mutualistic or pathogenic interactions and the immune response in the digestive niche. PMID- 26142682 TI - Shigella in baby bottles of a Brazilian newborn nursery. PMID- 26142683 TI - Vaccination and established microbiological testing is essential in managing cholera and Ebola infection. PMID- 26142684 TI - Zika: the new arbovirus threat for Latin America. PMID- 26142685 TI - Significant abnormalities of the HDL phosphosphingolipidome in type 1 diabetes despite normal HDL cholesterol concentration. AB - OBJECTIVE: Phospholipids and sphingolipids are major components of HDL. They play a critical role in HDL functionality and protective effects against atherosclerosis. As HDL are dysfunctional in type 1 diabetic patients, we ascertained whether they presented abnormalities in their phospholipid and sphingolipid profile, despite normal HDL cholesterol concentration. METHODS: Using liquid chromatography-tandem mass spectrometry, we quantified the main species of phosphatidylcholines, sphingomyelins, lysophophatidylcholines, phosphatidylethanolamines, phosphatidylinositols, ceramides, plasmalogens and sphingosines 1-phosphate in the HDL2 and HDL3 from 54 type 1 diabetic patients and 50 controls. RESULTS: Serum HDL cholesterol was similar in the 2 groups of subjects. When data were expressed relative to the total amount of phospholipids and sphingolipids, sphingosines-1-phosphate (S1P) were 11.7% (NS) and 14.4% (p = 0.0062) lower in HDL2 and HDL3, respectively, from type 1 diabetic patients than from controls. Ceramides were 23% (p = 0.005) and 24% (borderline significance) lower in HDL2 and HDL3, respectively. The concentration of apolipoprotein M, the carrier of S1P, was similar in patients and controls. In type 1 diabetic patients compared to controls, the concentration of d18:1-S1P, the main S1P species, was decreased in total plasma (-17.0%, p < 0.0001), HDL fraction (-21.9%, p < 0.0001) and non-HDL fraction (-13.7%, p = 0.012). The concentration of ceramides was decreased in total plasma (-24.4%, p < 0.0001), HDL fraction (-27.9%, p = 0.0006) and non-HDL fraction (-22.0%, p = 0.0087). CONCLUSION: Despite normal HDL cholesterol level, the phospholipid + sphingolipid profile is impaired in HDL from type 1 diabetic patients. These abnormalities, especially the decrease in S1P, could contribute to the impaired HDL functionality observed in these patients. PMID- 26142686 TI - Reliability of oscillometric central hemodynamic responses to an orthostatic challenge. AB - BACKGROUND: Monitoring central hemodynamic responses to an orthostatic challenge may provide important insight into autonomic nervous system function. Oscillometric pulse wave analysis devices have recently emerged, presenting clinically viable options for investigating central hemodynamic properties. The purpose of the current study was to determine whether oscillometric pulse wave analysis can be used to reliably (between-day) assess central blood pressure and central pressure augmentation (augmentation index) responses to a 5 min orthostatic challenge (modified tilt-table). METHODS: Twenty healthy adults (26.4 y (SD 5.2), 55% F, 24.7 kg/m(2) (SD 3.8)) were tested on 3 different mornings in the fasted state, separated by a maximum of 7 days. Central hemodynamic variables were assessed on the left arm using an oscillometric device. RESULTS: Repeated measures analysis of variance indicated a significant main effect of the modified tilt-table for all central hemodynamic variables (P < 0.001). In response to the tilt, central diastolic pressure increased by 4.5 mmHg (CI: 2.6, 6.4), central systolic blood pressure increased by 2.3 (CI: 4.4, 0.16) mmHg, and augmentation index decreased by an absolute - 5.3%, (CI: -2.7, -7.9%). The intra-class correlation coefficient values for central diastolic pressure (0.83-0.86), central systolic blood pressure (0.80-0.87) and AIx (0.79-0.82) were above the 0.75 criterion in both the supine and tilted positions, indicating excellent between-day reliability. CONCLUSION: Central hemodynamic responses to an orthostatic challenge can be assessed with acceptable between-day reliability using oscillometric pulse wave analysis. PMID- 26142687 TI - Loneliness is associated with poor prognosis in late-life depression: Longitudinal analysis of the Netherlands study of depression in older persons. AB - BACKGROUND: Although depression and loneliness are common among older adults, the role of loneliness on the prognosis of late-life depression has not yet been determined. Therefore, we examined the association between loneliness and the course of depression. METHODS: We conducted a 2-year follow-up study of a cohort from the Netherlands Study of Depression in Older Persons (NESDO). This included Dutch adults aged 60-90 years with a diagnosis of major depression, dysthymia, or minor depression according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We performed regression analyses to determine associations between loneliness at baseline and both severity and remission of depression at follow-up. We controlled for potential confounders and performed multiple imputations to account for missing data. RESULTS: Of the 285 respondents, 48% were still depressed after 2 years. Loneliness was independently associated with more severe depressive symptoms at follow-up (beta 0.61; 95% CI 0.12-1.11). Very severe loneliness was negatively associated with remission after 2 years compared with no loneliness (OR 0.25; 95% CI 0.08-0.80). LIMITATIONS: Despite using multiple imputation, the large proportion of missing values probably reduces the study's precision. Generalizability to the general population may be limited by the overrepresentation of ambulatory patients with possibly more persistent forms of depression. CONCLUSION: In this cohort, the prognosis of late-life depression was adversely affected by loneliness. Health care providers should seek to evaluate the degree of loneliness to obtain a more reliable assessment of the prognosis of late-life depression. PMID- 26142688 TI - Suggestibility as a predictor of response to antidepressants: A preliminary prospective trial. AB - BACKGROUND: The growing awareness that so many do not respond adequately to antidepressant (AD) pharmacotherapy has sparked research seeking to characterize those who do. While the pharmacological mechanisms of AD treatment have been extensively evaluated, much remains unknown about the placebo component of the response to medication. This study examined the association between suggestibility levels and response to ADs amongst depressed patients. METHODS: Twenty unipolar depression outpatients, recruited before starting AD monotherapy, received clear, standardized instructions that the therapeutic effects of AD, though not side effects, would require 2-4 weeks. At baseline (T1), 1 week (T2), and 1 month (T3), participants were evaluated for depressive symptoms, using the Hamilton Rating Scale for Depression-17 items (HAM-D); for anxiety by the Hamilton Rating Scale for Anxiety (HAM-A); for side effects by the Antidepressant Side Effect Checklist (ASEC); and for suggestibility, using the Multidimensional Iowa Suggestibility Scale (MISS). RESULTS: High levels of baseline suggestibility were associated with less improvement in depression level and more side-effects during the first week. In accordance with our hypothesis the more suggestible patients improved more between T2 and T3. No significant correlations were found between baseline suggestibility levels and change in anxiety. LIMITATIONS: Small sample size and a self-report questionnaire assessing suggestibility were limitations. CONCLUSION: This study offers a potentially new and clinically useful approach to understanding and predicting who will respond to AD treatment. Suggestibility seems to play a role, presumably by shaping expectation, in response to AD treatment. We hope that this avenue will be further explored. PMID- 26142689 TI - Multiplex immunoassay analysis of plasma shows differences in biomarkers related to manic or mixed mood states in bipolar disorder patients. AB - BACKGROUND: The molecular understanding of bipolar disorder (BD) aetiology has advanced over the last years through the identification of peripheral disease biomarkers. Here, we have attempted to identify plasma biomarkers associated with distinct BD mood states. METHODS: Plasma from BD patients with either a current manic (n=29) or mixed (n=17) mood state and healthy controls (n=53) were analysed using a multiplex immunoassay platform. A total of 145 hormones, growth factors, transport proteins and inflammatory factors were measured. RESULTS: Plasma levels of the hormones C-peptide, progesterone and insulin, and the inflammatory protein cancer antigen 125 were altered in both mood states. The hormone peptide YY and the growth factor trafficking protein sortilin were changed only in mania patients. Finally, the inflammatory factors haptoglobin, chemokine CC4 and matrix metalloproteinase 7 were altered specifically in mixed mood patients. LIMITATIONS: This study was limited by a small sample size, potential confounding effects of multiple drug treatments in the patient groups, and lack of dietary restrictions at sampling. CONCLUSIONS: Plasma from mania and mixed mood BD patients revealed similar changes in proteins related to insulin signalling, suggesting that these could be trait biomarkers. However, mania patients showed specific changes in hormonal and growth factor functions and mixed mood patients had a higher number of changes in inflammation-related molecules. Further studies of these and other biomarker candidates will increase our understanding of the systemic biological pathways affected in different BD mood states. This could lead to the identification of differential surrogate readouts and potential new drug targets for improved treatment outcomes. PMID- 26142690 TI - Late-life suicide: Insight on motives and contributors derived from suicide notes. AB - OBJECTIVES: The aims of this study were: (i) to investigate the proportion of older people writing suicide notes in New Zealand; (ii) to compare the socio demographic and clinical variables of older suicide note writers and non-note writers; and (iii) to perform a thematic analysis of the content of suicide notes. METHODS: The Coronial Services provided records of all suicide cases aged 65 years and over (n=225) between July 2007 and December 2012. We were able to determine whether there was a suicide note written in 212 cases. The content of 39 coroners/medical examiners' excerpts and 5 suicide notes was available for thematic analysis using a general inductive approach. FINDINGS: 88 (41.5%) older people left a suicide note. Logistic regression showed that female gender (OR=2.8, 95% CI=1.4-5.7, p=0.005) and Caucasian ethnicity (OR=13.7, 95% CI=1.7 111.0, p=0.014) are significantly associated with older people writing suicide notes. 33.3% of those who left a suicide note gave health-related reasons for their suicide and a significant proportion (73.3%) of them had underlying medical conditions. Another common theme is around people leaving specific instructions and wishes. CONCLUSIONS: Apart from gender and ethnicity, suicide note writers are similar to non-writers on broad socio-demographic and clinical factors. Suicide notes indicated free will in and reasons for their suicide and emotional/farewell messages to their loved ones. Many documented poor quality of life or physical illness but the progression of these factors to suicide in older people should be further researched. PMID- 26142691 TI - Influence of anxiety symptoms on improvement of neurocognitive functions in patients with major depressive disorder: A 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study. AB - BACKGROUND: Previous research has reported evidence that patients with major depressive disorder (MDD) show anxiety symptoms and neurocognitive impairments. However, the influence of anxiety on neurocognitive function in MDD patients during antidepressant treatment is unclear. METHOD: MDD patients (n=164) completed a 12-week, multicenter, randomized trial assigned in a 1:1 ratio to either tianeptine or escitalopram. Changes of anxiety symptoms were assessed by the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D), self-rated subjective cognitive impairment on memory and concentration, the Mini-Mental Status Examination (MMSE), Continuous Performance Test (CPT), Verbal Learning Test (VLT), and Raven's Progressive Matrices (RPM) were assessed every 4 weeks. RESULTS: During 12 weeks of treatment, decrease in the HAM-A score was significantly associated with improvement of subjective cognitive impairments on memory (p<0.001) and concentration (p<0.001), and objective measures on delayed memory (p=0.006) and reasoning ability (p=0.002), after adjusting for covariates such as baseline HAM-A scores, time, sex, age, education years and assigned medication using the Mixed effects and Generalized Estimated Equation model analysis. However, the other cognitive outcome variables, immediate memory, commission error, and MMSE, which showed significant improvement through 12-week study period, showed no significant association with improvement of anxiety. CONCLUSION: Improvement of anxiety symptoms was significantly associated with improvement in subjective and objective neurocognitive functions such as delayed memory and reasoning ability in elderly MDD patients during antidepressant treatment, but not significantly associated with improvement of immediate memory and commission error. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01309776. PMID- 26142692 TI - Applications and advances of metabolite biosensors for metabolic engineering. AB - Quantification and regulation of pathway metabolites is crucial for optimization of microbial production bioprocesses. Genetically encoded biosensors provide the means to couple metabolite sensing to several outputs invaluable for metabolic engineering. These include semi-quantification of metabolite concentrations to screen or select strains with desirable metabolite characteristics, and construction of dynamic metabolite-regulated pathways to enhance production. Taking inspiration from naturally occurring systems, biosensor functions are based on highly diverse mechanisms including metabolite responsive transcription factors, two component systems, cellular stress responses, regulatory RNAs, and protein activities. We review recent developments in biosensors in each of these mechanistic classes, with considerations towards how these sensors are engineered, how new sensing mechanisms have led to improved function, and the advantages and disadvantages of each of these sensing mechanisms in relevant applications. We particularly highlight recent examples directly using biosensors to improve microbial production, and the great potential for biosensors to further inform metabolic engineering practices. PMID- 26142693 TI - On the relevance of disorder in athermal amorphous materials under shear. AB - We show that, at least at a mean-field level, the effect of structural disorder in sheared amorphous media is very dissimilar depending on the thermal or athermal nature of their underlying dynamics. We first introduce a toy model, including explicitly two types of noise (thermal versus athermal). Within this interpretation framework, we argue that mean-field athermal dynamics can be accounted for by the so-called Hebraud-Lequeux (HL) model, in which the mechanical noise stems explicitly from the plastic activity in the sheared medium. Then, we show that the inclusion of structural disorder, by means of a distribution of yield energy barriers, has no qualitative effect in the HL model, while such a disorder is known to be one of the key ingredients leading kinematically to a finite macroscopic yield stress in other mean-field descriptions, such as the Soft-Glassy-Rheology model. We conclude that the statistical mechanisms at play in the emergence of a macroscopic yield stress, and a complex stationary dynamics at low shear rate, are different in thermal and athermal amorphous systems. PMID- 26142694 TI - Bubble formation in water with addition of a hydrophobic solute. AB - We show that phase separation can occur in a one-component liquid outside its coexistence curve (CX) with addition of a small amount of a solute. The solute concentration at the transition decreases with increasing the difference of the solvation chemical potential between liquid and gas. As a typical bubble-forming solute, we consider O2 in ambient liquid water, which exhibits mild hydrophobicity and its critical temperature is lower than that of water. Such a solute can be expelled from the liquid to form gaseous domains while the surrounding liquid pressure is higher than the saturated vapor pressure p cx. This solute-induced bubble formation is a first-order transition in bulk and on a partially dried wall, while a gas film grows continuously on a completely dried wall. We set up a bubble free energy DeltaG for bulk and surface bubbles with a small volume fraction phi. It becomes a function of the bubble radius R under the Laplace pressure balance. Then, for sufficiently large solute densities above a threshold, DeltaG exhibits a local maximum at a critical radius and a minimum at an equilibrium radius. We also examine solute-induced nucleation taking place outside CX, where bubbles larger than the critical radius grow until attainment of equilibrium. PMID- 26142695 TI - Computational prediction of octanol-water partition coefficient based on the extended solvent-contact model. AB - The logarithm of 1-octanol/water partition coefficient (LogP) is one of the most important molecular design parameters in drug discovery. Assuming that LogP can be calculated from the difference between the solvation free energy of a molecule in water and that in 1-octanol, we propose a method for predicting the molecular LogP values based on the extended solvent-contact model. To obtain the molecular solvation free energy data for the two solvents, a proper potential energy function was defined for each solvent with respect to atomic distributions and three kinds of atomic parameters. Total 205 atomic parameters were optimized with the standard genetic algorithm using the training set consisting of 139 organic molecules with varying shapes and functional groups. The LogP values estimated with the two optimized solvation free energy functions compared reasonably well with the experimental results with the associated squared correlation coefficient and root mean square error of 0.824 and 0.697, respectively. Besides the prediction accuracy, the present method has the merit in practical applications because molecular LogP values can be computed straightforwardly from the simple potential energy functions without the need to calculate various molecular descriptors. The methods for enhancing the accuracy of the present prediction model are also discussed. PMID- 26142696 TI - In vitro evaluation of the cytotoxicity and modulation of mechanisms associated with inflammation induced by perfluorooctanesulfonate and perfluorooctanoic acid in human colon myofibroblasts CCD-18Co. AB - Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the most notable members of an emerging class of persistent organic pollutants (POPs), poly- and perfluoroalkyl acids (PFASs). In this study, the CCD-18Co myofibroblasts were selected as a cell model to investigate the cytotoxic effects of PFOS and PFOA. The aim was to perform an in vitro evaluation of the ability of these compounds to induce cytotoxicity and modulate mechanisms associated with inflammation as measured by (i) colon fibroblasts viability, (ii) colon fibroblasts proliferation, and (iii) IL-6 production. The data provided in this study suggest that PFOS and PFOA can have cytotoxic potential and modulate processes associated with intestinal inflammation such as myofibroblasts proliferation and IL-6 production at concentrations similar to those detected in vivo. Our results also highlight the influence of culture serum concentration in cytotoxic in vitro studies, which should be considered in future toxicity studies involving PFOS and PFOA. The results contribute to a better knowledge of the effects of PFOS and PFOA in human cells, a phenomenon still not fully examined. PMID- 26142697 TI - Interface segregation behavior in thermal aged austenitic precipitation strengthened stainless steel. AB - The segregation of various elements at grain boundaries, precipitate/matrix interfaces were analyzed using atom probe tomography in an austenitic precipitation strengthened stainless steel aged at 750 degrees C for different time. Segregation of P, B and C at all types of interfaces in all the specimens were observed. However, Si segregated at all types of interfaces only in the specimen aged for 16 h. Enrichment of Ti at grain boundaries was evident in the specimen aged for 16 h, while Ti did not segregate at other interfaces. Mo varied considerably among interface types, e.g. from segregated at grain boundaries in the specimens after all the aging time to never segregate at gamma'/gamma phase interfaces. Cr co-segregated with C at grain boundaries, although carbides still did not nucleate at grain boundaries yet. Despite segregation tendency variations in different interface types, the segregation tendency evolution variation of different elements depending aging time were analyzed among all types of interfaces. Based on the experimental results, the enrichment factors, Gibbs interface excess and segregation free energies of segregated elements were calculated and discussed. PMID- 26142698 TI - High-level expression, purification and characterization of carbazole dioxygenase, a three components dioxygenase, of Pseudomonas GBS.5. AB - OBJECTIVE: To investigate the conversion of carbazole into 2'-aminobiphenyl-2,3 diol using carbazole dioxygenase (CARDO) that is a multicomponent enzyme consisting of homotrimeric terminal oxygenases (CarAa), a ferredoxin (CarAc) and a ferredoxin reductase (CarAd) unit, encoded by the carAa, carAc and carAd genes, respectively. RESULTS: The enzyme subunits containing a GST tag were expressed independently in E. coli. The expressed proteins were purified by one-step immobilized affinity chromatography and three purified proteins could reconstitute the CARDO activity in vitro and showed activity against carbazole as well as against wide range of polyaromatic compounds. CONCLUSION: This method provides an efficient way to obtain an active carbazole dioxygenase with high yield, high purity and with activity against a wide range of polyaromatic compounds. PMID- 26142700 TI - Phenotype and function of tissue-resident unconventional Foxp3-expressing CD4(+) regulatory T cells. AB - It is becoming increasingly clear that regulatory T cells (Treg cells) in specific tissues are important parts of immune system. Tissue-resident Treg cells, which are largely Foxp3-expressing CD4(+) Treg cells, are distinct from one another and conventional Treg cells, and have tissue-specific phenotype and function. They have roles in improving insulin sensitivity in adipose tissue, promoting muscle repair, limiting inflammation in intestine, skin and central nervous system. In this Review, we discuss the current understanding of phenotype and function of tissue-resident Treg cells. Understanding phenotypic and functional diversity in different tissues could provide new insight into Treg cells development and investigation. PMID- 26142701 TI - Efferocytosis: Burying cell corpses to regulate tolerance and immunity. PMID- 26142699 TI - Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate. AB - Dichloroacetate (DCA) and pyruvate activate pyruvate dehydrogenase (PDH), a key enzyme that modulates glucose oxidation and mitochondrial NADH production. Both compounds improve recovery after ischemia in isolated hearts. However, the action of DCA and pyruvate in normoxic myocardium is incompletely understood. We measured the effect of DCA and pyruvate on contraction, mitochondrial redox state, and intracellular calcium cycling in isolated rat hearts during normoxic perfusion. Normalized epicardial NADH fluorescence (nNADH) and left ventricular developed pressure (LVDP) were measured before and after administering DCA (5 mM) or pyruvate (5 mM). Optical mapping of Rhod-2AM was used to measure cytosolic calcium kinetics. DCA maximally activated PDH, increasing the ratio of active to total PDH from 0.48 +/- 0.03 to 1.03 +/- 0.03. Pyruvate sub-maximally activated PDH to a ratio of 0.75 +/- 0.02. DCA and pyruvate increased LVDP. When glucose was the only exogenous fuel, pyruvate increased nNADH by 21.4 +/- 2.9 % while DCA reduced nNADH by 21.4 +/- 6.1 % and elevated the incidence of premature ventricular contractions (PVCs). When lactate, pyruvate, and glucose were provided together as exogenous fuels, nNADH increased with DCA, indicating that PDH activation with glucose as the only exogenous fuel depletes PDH substrate. Calcium transient time-to-peak was shortened by DCA and pyruvate and SR calcium re-uptake was 30 % longer. DCA and pyruvate increased SR calcium load in myocyte monolayers. Overall, during normoxia when glucose is the only exogenous fuel, DCA elevates SR calcium, increases LVDP and contractility, and diminishes mitochondrial NADH. Administering DCA with plasma levels of lactate and pyruvate mitigates the drop in mitochondrial NADH and prevents PVCs. PMID- 26142702 TI - Catalytically inactive telomerase in oncogenesis. PMID- 26142703 TI - Ubiquitin regulates dissociation of DNA repair factors from chromatin. PMID- 26142704 TI - Peptide-siRNA nanotherapeutics in arthritis. PMID- 26142705 TI - Heme oxygenase-1: for better, for worse, in sickness and in health. PMID- 26142706 TI - Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies. AB - Cholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies. Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy. Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease. A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease. PMID- 26142709 TI - [Sinonasal mucormycosis revealed by a necrotic velar ulceration]. AB - INTRODUCTION: Mucormycosis is a deep mycosis which has been spreading out in recent years. It is still poorly understood and poorly described in sub-Saharan Africa. The authors report a case of sinonasal localization, of fatal evolution and late diagnosis in a young child. OBSERVATION: It is about a 13-year-old child suffering from chronic rhinosinus syndrome for two years. He was observed in stomatology for a necrotic velar ulceration that have occurred for three months. The clinical, radiological and histological explorations were in favor of a sinonasal mucormycosis. The administration of amphotericin B and the surgical treatment did not slow down the fatal evolution. CONCLUSION: Mucormycosis should not be dealt with any diagnostic error and no therapeutic improvisation. It has to be thought about when dealing with a rhinosinusal syndrome with cleft ulceration. PMID- 26142707 TI - Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline. AB - In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to high concentrations and affects multiple signaling pathways that are crucial for lymphomagenesis. Our data reveal the deneddylating activity of COP-9 signalosome (CSN) as a novel target of doxycycline and suggest that doxycycline may exert its effects in DLBCL cells in part through a CSN5-HSP90 pathway. Consistently, knockdown of CSN5 exhibited similar effects as doxycycline treatment on DLBCL cell survival and HSP90 chaperone function. In addition to DLBCL cells, doxycycline inhibited growth of several other types of non-Hodgkin lymphoma cells in vitro. Together, our results suggest that doxycycline may represent a promising therapeutic agent for DLBCL and other non-Hodgkin lymphomas subtypes. PMID- 26142708 TI - VGF expression by T lymphocytes in patients with Alzheimer's disease. AB - Secretion of VGF is increased in cerebrospinal fluid and blood in neurodegenerative disorders like Alzheimer's disease (AD) and VGF is a potential biomarker for these disorders. We have shown that VGF is expressed in peripheral T cells and is correlated with T cell survival and cytokine secretion. The frequency of VGF+CD3+ T cells increases with normal aging. We found an increased number of VGF-expressing T cells in patients with AD compared to aged healthy controls, which was associated with enhanced HbA1c levels in blood. Upon treatment with rivastigmine, T cell proliferation and VGF expression in AD patients decreased to the level found in controls. Moreover, rapamycin treatment in vitro reduced the number of VGF+CD3+ cells in AD patients to control levels. PMID- 26142710 TI - Protective effects of aloperine on neonatal rat primary cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion. AB - Aloperine (ALO), one of the alkaloids isolated from Sophora alopecuroides L., is traditionally used for various diseases including neuronal disorders. This study investigated the protective effects of ALO on neonatal rat primary-cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion (OGD/RP). Treatment with ALO (25, 50, and 100 mg/l) attenuated neuronal damage (p < 0.01), with evidence of increased cell viability (p < 0.01) and decreased cell morphologic impairment. Furthermore, ALO increased mitochondrial membrane potential (p < 0.01), but inhibited intracellular-free calcium [Ca(2+)] i (p < 0.01) elevation in a dose-dependent manner at OGD/RP. ALO also reduced the intracellular reactive oxygen species and malondialdehyde production and enhanced the antioxidant enzymatic activities of catalase, superoxide dismutase, glutathione peroxidase and the total antioxidant capacity. The results suggested that ALO has significant neuroprotective effects that can be attributed to anti oxidative stress. PMID- 26142711 TI - Early Application of Permanent Metallic Mesh Stent in Substitution for Temporary Polymeric Ureteral Stent Reduces Unnecessary Ureteral Procedures in Patients With Malignant Ureteral Obstruction. AB - OBJECTIVE: To identify risk factors for metal stent failure in patients who received polymeric double J (PDJ) ureteral stents for malignant ureteral obstructions (MUOs) and review our clinical experiences using a ureteral metallic stent. PATIENTS AND METHODS: Patients who underwent metallic stent placement to replace a double J ureteral stent for nonurological MUO between January 2011 and February 2014 were included. The collected data included gender, age, laterality, cause of obstruction, PDJ ureteral stenting duration, immediate success of the metal stent, and additional procedures to relieve obstruction after metal stenting (eg, additional metal stenting or percutaneous nephrostomy (PCN) indwelling catheter placement). Cox regression tests were used for the statistical analyses. RESULTS: In this analysis 40 ureteral units were included. There was no initial technical failure. However, 9 (22.5%) units required additional procedures due to de novo ureteral obstruction, including additional indwelling metal stents (7.5%), additional PDJ stenting (10%), or indwelling percutaneous nephrostomy (5%). Univariate and multivariate analyses revealed that the duration of previous PDJ ureteral stenting was an independent prognostic factor for predicting ureteral metal stent failure (hazard ratio = 1.063, 95% confidence interval = 1.004-1.125; P = .037). CONCLUSION: Long-term indwelling of a PDJ ureteral stent increases the risk of additional management for de novo ureteral stricture after ureteral metal stent replacement for nonurological MUO. Our data suggest that careful patient selection and counseling for those at high risk are needed when metal stent replacement is considered for patients with long term PDJ ureteral stents for MUO. PMID- 26142712 TI - Acute Urinary Retention Rates in the General Male Population and in Adult Men With Lower Urinary Tract Symptoms Participating in Pharmacotherapy Trials: A Literature Review. AB - Despite proven efficacy, antimuscarinics are not frequently used for treating lower urinary tract symptoms in adult men, due to the perception of an increased risk of acute urinary retention (AUR). Men treated with alpha-blockers, 5alpha reductase inhibitors, or their combinations have lower AUR incidence rates than the general symptomatic population. In the selected study population in this review (men with post-void residuals <=200 mL), the risk of AUR with antimuscarinics with and/or without alpha-blockers may be increased during short term treatment, but if patients do not develop AUR in the first 3 months, their subsequent risk is lower than in the untreated, symptomatic population. PMID- 26142713 TI - Using the Vibrance Kegel Device With Pelvic Floor Muscle Exercise for Stress Urinary Incontinence: A Randomized Controlled Pilot Study. AB - OBJECTIVE: To evaluate the effectiveness of pelvic floor muscle exercises (PFMEs) performed with the new biofeedback Vibrance Kegel Device (VKD), compared to PFMEs alone, in treating stress urinary incontinence (SUI). MATERIALS AND METHODS: This was a pilot prospective, randomized trial of women aged >=18 years with SUI symptoms who underwent PFMEs at University Malaya Medical Centre from October 2011 to October 2013. The patients were randomly divided into two groups: control (PFMEs alone) and VKD (PFMEs with VKD biofeedback). The patients underwent 16 weeks of pelvic floor training, during which they were assessed using Australian pelvic floor questionnaires and modified Oxford scales for pelvic floor muscle strength at week 0, 4, and 16. RESULTS: Forty patients were recruited (control 19, VKD 21). Three patients in the control group dropped out during week 16 training, whereas the VKD group had no dropouts. The VKD group reported significantly earlier improvement in SUI scores, as assessed by the Australian pelvic floor questionnaires (P = .035) at week 4. However, there was no significant difference between the groups' SUI scores at week 16. Pelvic floor muscle strength was significantly better in the VKD group at week 4 (P = .025) and week 16 (P = 0.001). The subjective cure rate was similar in both groups at week 16 (62.5% for control and 61.9% for VKD) (P = 0.742). CONCLUSION: Using the VKD resulted in significant early improvement in SUI scores, and pelvic muscle strength had improved significantly by the end of the study. The VKD proved useful as an adjunct for pelvic floor training. PMID- 26142714 TI - Outcomes of the Endoscopic Treatment of Bladder Neck Contractures in the Orthotopic Neobladder. AB - OBJECTIVE: To examine the outcomes of endoscopic procedures for bladder neck contracture (BNC) in the orthotopic neobladder (ONB) after radical cystectomy focusing on success rates for patients who require multiple treatments. MATERIALS AND METHODS: Patients who underwent treatment for cystoscopically confirmed BNC in an ONB from 2007 to 2014 were studied. Treatment information included procedure type, use of adjuvant clean intermittent catheterization (CIC), and follow-up procedures. Procedures followed by additional interventions were categorized as failures. Success was defined as no additional surgical procedure with at least 1 year of follow-up. Procedures were classified by a number of prior endoscopic treatments. RESULTS: Seventy-one patients underwent 155 individual endoscopic procedures (146 urethrotomy, 3 dilation, and 6 transurethral resection of bladder neck). All patients were male without prior radiation. Median follow-up after initial endoscopic treatment was 26.8 months (interquartile range: 16.6-51.7), and time to recurrence was 3.5 months (1.6 6.3). Success was experienced for 50 of 136 individual procedures (37%) after excluding 19 procedures for inadequate follow-up. Success rates remained 25%-43% even after multiple prior interventions. Adjuvant CIC was associated with a higher success rate (14/24 or 58%) compared to procedures without CIC (36/112 or 32%, P = .02). Successful outcomes were seen in 50 of 71 patients (73%) with 2 patients requiring ONB removal. CONCLUSION: Individual endoscopic treatments of BNC in the ONB were met with 37% success. The rate did not decrease with subsequent procedures. Adjuvant CIC improved the outcomes. Overall, a successful outcome was achieved for most patients, but the majority required more than one procedure. PMID- 26142715 TI - Does Postoperative Leukocyturia Influence Treatment Outcomes After Photoselective Vaporization of the Prostate (PVP)? A Prospective Short-Term Serial Follow-Up Study. AB - OBJECTIVE: To identify serial changes in the incidence of leukocyturia after photoselective laser-vaporization of the prostate (PVP), to determine whether postoperative leukocyturia could be associated with surgical outcomes, and to identify predictors of persistent leukocyturia after PVP. PATIENTS AND METHODS: A total of 102 men without leukocyturia on baseline urinalysis but underwent PVP were included in this prospective study. Treatment outcomes were assessed at 1 week, and 1, 3, 6, and 12 months postoperatively using International Prostate Symptom Score, Overactive Bladder Symptom Score (OABSS), uroflowmetry, postvoid residual, urinalysis, urine culture, and serum prostate-specific antigen (PSA). RESULTS: The incidences of leukocyturia and dysuria at 1 week, and 1, 3, and 6 months postoperatively were 100.0%, 51.0%, 19.6%, and 0.0% and 30.3%, 25.4%, 5.9%, and 0.0%, respectively. Only one case of bacteriuria occurred throughout the entire follow-up period. At 1 month postoperatively, decrease in subtotal storage symptoms score, quality-of-life index, and total OABSS in patients without leukocyturia were significantly greater than in those with leukocyturia. At 3 months postoperatively, patients without leukocyturia showed greater improvement in subtotal storage symptoms score, total OABSS, quality-of-life index, bladder voiding efficiency, and postvoid residual compared with those with leukocyturia. On logistic regression analysis, age, PSA, prostate size, and amount of energy utilized were independent predictors of persistent leukocyturia 3 months after surgery. CONCLUSION: Leukocyturia is observed in all patients immediately after PVP, but its incidence decreases with time. It may have adverse effects on treatment outcomes. Also, older age, higher serum PSA, larger prostate size, and greater amount of energy utilized may be risk factors of persistent leukocyturia. PMID- 26142716 TI - Can Bladder Wall Thickness Measurement Be Used for Detecting Bladder Outlet Obstruction? AB - OBJECTIVE: To investigate the relationship between bladder wall thickness (BWT) and uroflowmetric parameters and the International Prostate Symptoms Score (IPSS) in patients with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: A total of 236 male patients who had LUTS-related benign prostatic enlargement with serum prostate-specific antigen level <=4 ng/mL were included in this study. Age and duration of LUTS and IPSS were recorded. BWT was measured using 7.5 mHz suprapubic ultrasonography before uroflowmetry and postvoid residual (PVR) was calculated thereafter. The relationship between BWT and poor indicators for bladder outlet obstruction (BOO) (IPSS >19, Qmax <15 mL/min, PVR >100 cm(3)) was investigated. RESULTS: The mean age was 62.5 +/- 8.1 (39-77) years and the mean BWT was 3.8 +/- 1.5 (1.4-8.7) mm. The mean IPSS, Qmax, PVR, and duration of LUTS were 17.7, 13.7 mL/min, 89.9, and 46.5 months, respectively. A positive correlation was found between BWT and IPSS, PVR and duration of LUTS, whereas a negative correlation was found between BWT and Qmax (P <.001). BWT increased when number of BOO parameters increased. BWT was 2.9 in patients without BOO parameters whereas BWT was 3.5, 4.1, and 4.5 mm in patients with any one, any two, and all parameters of BOO, respectively. CONCLUSION: BWT increased when number of BOO parameters increased. We believe that measurement of BWT is an easy, quick, and repeatable test to predict BOO severity. PMID- 26142717 TI - Reply to Letter to the Editor: The Current State of Urologic Malpractice in Spain. PMID- 26142718 TI - Polybrominated diphenyl ethers (PBDEs) in dust from primary schools in South East Queensland, Australia. AB - PBDE concentrations are higher in children compared to adults with exposure suggested to include dust ingestion. Besides the home environment, children spend a great deal of time in school classrooms which may be a source of exposure. As part of the "Ultrafine Particles from Traffic Emissions and Children's Health (UPTECH)" project, dust samples (n=28) were obtained in 2011/12 from 10 Brisbane, Australia metropolitan schools and analysed using GC and LC-MS for polybrominated diphenyl ethers (PBDEs) -17, -28, -47, -49, -66, -85, -99, -100, -154, -183, and 209. Sigma11PBDEs ranged from 11-2163 ng/g dust; with a mean and median of 600 and 469 ng/g dust, respectively. BDE-209 (range n.d. -2034 ng/g dust; mean (median) 402 (217)ng/g dust) was the dominant congener in most classrooms. Frequencies of detection were 96%, 96%, 39% and 93% for BDE-47, -99, -100 and 209, respectively. No seasonal variations were apparent and from each of the two schools where XRF measurements were carried out, only two classroom items had detectable bromine. PBDE intake for 8-11 year olds can be estimated at 0.094 ng/day BDE-47; 0.187 ng/day BDE-99 and 0.522ng/day BDE-209 as a result of ingestion of classroom dust, based on mean PBDE concentrations. The 97.5% percentile intake is estimated to be 0.62, 1.03 and 2.14 ng/day for BDEs-47, -99 and -209, respectively. These PBDE concentrations in dust from classrooms, which are higher than in Australian homes, may explain some of the higher body burden of PBDEs in children compared to adults when taking into consideration age dependant behaviours which increase dust ingestion. PMID- 26142719 TI - Social deprivation and population density are not associated with small area risk of amyotrophic lateral sclerosis. AB - INTRODUCTION: Evidence of an association between areal ALS risk and population density has been previously reported. We aim to examine ALS spatial incidence in Ireland using small areas, to compare this analysis with our previous analysis of larger areas and to examine the associations between population density, social deprivation and ALS incidence. METHODS: Residential area social deprivation has not been previously investigated as a risk factor for ALS. Using the Irish ALS register, we included all cases of ALS diagnosed in Ireland from 1995-2013. 2006 census data was used to calculate age and sex standardised expected cases per small area. Social deprivation was assessed using the pobalHP deprivation index. Bayesian smoothing was used to calculate small area relative risk for ALS, whilst cluster analysis was performed using SaTScan. The effects of population density and social deprivation were tested in two ways: (1) as covariates in the Bayesian spatial model; (2) via post-Bayesian regression. RESULTS: 1701 cases were included. Bayesian smoothed maps of relative risk at small area resolution matched closely to our previous analysis at a larger area resolution. Cluster analysis identified two areas of significant low risk. These areas did not correlate with population density or social deprivation indices. DISCUSSION: Two areas showing low frequency of ALS have been identified in the Republic of Ireland. These areas do not correlate with population density or residential area social deprivation, indicating that other reasons, such as genetic admixture may account for the observed findings. PMID- 26142720 TI - Levels of perfluoroalkyl substances and risk of coronary heart disease: Findings from a population-based longitudinal study. AB - BACKGROUND: Cross-sectional studies have shown an association between exposure to perfluoroalkyl substances (PFASs) and coronary heart disease (CHD). These findings need to be evaluated in longitudinal settings. OBJECTIVES: To investigate the risk of CHD in relation to PFAS levels in a longitudinal setting among Swedish rural residents. METHODS: In a population-based prospective cohort of male farmers and rural residents recruited in 1990-1991, all men who received a CHD diagnosis between 1992 and 2009 were identified from national registers (n=253). For each CHD case, one control, matched for age, was chosen randomly from the cohort. For all cases and controls, levels of eight PFASs at baseline were measured in stored blood samples. In addition, for a subsample, PFAS levels were also measured in serum samples collected at a follow-up in 2002-2003. RESULTS: There were no statistically significant associations between levels of seven of the eight PFASs at baseline and risk for developing CHD. There was a significant association between perfluoroheptanoic acid (PFHpA) and CHD (OR=2.72; 95% CI: 1.52, 4.84) for the 3rd quartile and (OR=2.45; 95% CI: 1.40, 4.29) for the 4th quartile compared to the lowest quartile. Changes in levels of PFCs between baseline and follow-up did not differ systematically between cases and controls. CONCLUSIONS: This longitudinal study does not lend support to the previously reported cross-sectional relationship between PFAS levels and CHD risk. We found a significant association with PFHpA, but this could be a chance finding, considering its chemical resemblance to other PFASs. PMID- 26142721 TI - Disease Burden in the Treatment of Age-Related Macular Degeneration: Findings From a Time-and-Motion Study. AB - PURPOSE: To examine the time burden of managing neovascular age-related macular degeneration (AMD) imposed on physicians, staff, patients, and caregivers. DESIGN: Mixed-methods, prospective, observational time-and-motion study. METHODS: The multicenter study was conducted from March 2011 through August 2012. Retina specialists administering >=50 vascular endothelial growth factor (VEGF) inhibitor injections monthly were surveyed and completed records for >=5 patients scheduled for office visits within 3 weeks for anti-VEGF injection or monitoring. A survey was administered to 75 neovascular AMD patients aged >=50 years who received >=1 anti-VEGF injection in the past 6 months. Telephone interviews were conducted with 13 neovascular AMD patient caregivers. RESULTS: Fifty-six physicians provided data for 221 patients with neovascular AMD. Patients accounted for 20% of the health care staff's time per week, with an average of 23 staff members. An average patient visit for neovascular AMD was 90 minutes (range: 13 minutes to >4 hours). Patients reported an average time per visit of almost 12 hours, including preappointment preparation (16 minutes), travel (66 minutes), waiting time (37 minutes), treatment time (43 minutes), and postappointment recovery (9 hours). Patients stated that caregivers took time away from work (22%) and personal activities (28%) to provide transportation to appointments. CONCLUSIONS: Neovascular AMD management imposes a substantial time burden on physicians, staff, patients, and caregivers. There may be a need for additional support and/or reimbursement for services required by patients and caregivers and provided by physicians. PMID- 26142722 TI - Compromised epidermal barrier stimulates Harderian gland activity and hypertrophy in ACBP-/- mice. AB - Acyl-CoA binding protein (ACBP) is a small, ubiquitously expressed intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity and specificity. We have recently shown that targeted disruption of the Acbp gene leads to a compromised epidermal barrier and that this causes delayed adaptation to weaning, including the induction of the hepatic lipogenic and cholesterogenic gene programs. Here we show that ACBP is highly expressed in the Harderian gland, a gland that is located behind the eyeball of rodents and involved in the production of fur lipids and lipids used for lubrication of the eye lid. We show that disruption of the Acbp gene leads to a significant enlargement of this gland with hypertrophy of the acinar cells and increased de novo synthesis of monoalkyl diacylglycerol, the main lipid species produced by the gland. Mice with conditional targeting of the Acbp gene in the epidermis recapitulate this phenotype, whereas generation of an artificial epidermal barrier during gland development reverses the phenotype. Our findings indicate that the Harderian gland is activated by the compromised epidermal barrier as an adaptive and protective mechanism to overcome the barrier defect. PMID- 26142724 TI - Use of Journal Clubs Within Senior Capstone Courses: Analysis of Perceived Gains in Reviewing Scientific Literature. PMID- 26142723 TI - Positive selection in octopus haemocyanin indicates functional links to temperature adaptation. AB - BACKGROUND: Octopods have successfully colonised the world's oceans from the tropics to the poles. Yet, successful persistence in these habitats has required adaptations of their advanced physiological apparatus to compensate impaired oxygen supply. Their oxygen transporter haemocyanin plays a major role in cold tolerance and accordingly has undergone functional modifications to sustain oxygen release at sub-zero temperatures. However, it remains unknown how molecular properties evolved to explain the observed functional adaptations. We thus aimed to assess whether natural selection affected molecular and structural properties of haemocyanin that explains temperature adaptation in octopods. RESULTS: Analysis of 239 partial sequences of the haemocyanin functional units (FU) f and g of 28 octopod species of polar, temperate, subtropical and tropical origin revealed natural selection was acting primarily on charge properties of surface residues. Polar octopods contained haemocyanins with higher net surface charge due to decreased glutamic acid content and higher numbers of basic amino acids. Within the analysed partial sequences, positive selection was present at site 2545, positioned between the active copper binding centre and the FU g surface. At this site, methionine was the dominant amino acid in polar octopods and leucine was dominant in tropical octopods. Sites directly involved in oxygen binding or quaternary interactions were highly conserved within the analysed sequence. CONCLUSIONS: This study has provided the first insight into molecular and structural mechanisms that have enabled octopods to sustain oxygen supply from polar to tropical conditions. Our findings imply modulation of oxygen binding via charge-charge interaction at the protein surface, which stabilize quaternary interactions among functional units to reduce detrimental effects of high pH on venous oxygen release. Of the observed partial haemocyanin sequence, residue 2545 formed a close link between the FU g surface and the active centre, suggesting a role as allosteric binding site. The prevalence of methionine at this site in polar octopods, implies regulation of oxygen affinity via increased sensitivity to allosteric metal binding. High sequence conservation of sites directly involved in oxygen binding indicates that functional modifications of octopod haemocyanin rather occur via more subtle mechanisms, as observed in this study. PMID- 26142725 TI - The Food Environment Through the Camera Lenses of 9- to 13-Year-Olds Living in Urban, Low-Income, Midwestern Households: A Photovoice Project. AB - OBJECTIVE: To pilot Photovoice methodology with low-income, urban 9- to 13-year olds to gain insight about their food environment and to determine whether this methodology was engaging and acceptable to them. METHODS: Photovoice methodology was used to allow children to represent their food environment. Twenty male and 9 female, low-income, 9- to 13-year-old children participated. Quantitative photograph analysis included quantity taken and usable internal/external and social environment and healthfulness categorizations. Qualitative analysis was conducted through open coding of interview transcripts. RESULTS: A total of 345 usable photos were taken by the children (n = 29), depicting both healthy and unhealthy foods. Four themes were identified (1) food characteristics; (2) social environment; (3) kitchen, cooking, and dining environments; and (4) food insecurity. Unhealthy food was most readily available to children. Children reported a lack of functioning kitchen equipment and multiple physical and environmental challenges to consuming a healthy diet. Food insecurity was prevalent. Food stamps and food pantries were used to fill gaps in the home food supply. CONCLUSIONS AND IMPLICATIONS: Photovoice can be effective in engaging children in conversation about their food environment and increases understanding of their experiences with food. Photovoice can provide insight into the household food environments. This information can be used to tailor interventions to better reflect the living environment and eating behaviors in low-income populations. PMID- 26142726 TI - The Functionality Assessment Flowchart (FAF): a new simple and reliable method to measure performance status with a high percentage of agreement between observers. AB - BACKGROUND: Performance status (PS) assessment is an integral part of the decision-making process in cancer care. Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) PS are the most widely used tools. In some studies, the absolute agreement rate of these tools between observers has been moderate to low. The present study aimed to evaluate the inter-observer reliability and construct validity of the new Functionality Assessment Flowchart (FAF) and compare it with ECOG PS and KPS in a sample of cancer patients. METHODS: The patients were recruited by convenience from the waiting rooms of the Breast and Gynecology Ambulatory in a cross-sectional study. Two trained medical students (observer A) and five medical oncologists (observers B) independently rated women according to the ECOG PS, KPS and FAF. After the determining the PS scores, observer A administered the Functional Assessment of Cancer Therapy Fatigue (FACT-F) questionnaire to the participants. The agreements between observers A and B were investigated using the absolute agreement rate (%), weighted and unweighted kappa and Spearman's correlation test. For construct validity, the PS scores were correlated with functional and fatigue scores by performing correlation analysis. RESULTS: Eighty women with a median age of 57 years were included in the study (86% accrual rate). Among these women, 39 (48.8%) had advanced cancer. The overall absolute agreement rate between observers was 49.4% for KPS, 67% for ECOG PS, and 78.2% for FAF. When using unweighted kappa values, the inter-observer reliability was "fair", "moderate" and "substantial" for KPS, ECOG PS and FAF, respectively. However, when using weighted kappa statistics, "substantial" agreement was observed for KPS and ECOG PS and "nearly perfect" agreement was observed for FAF. All of the PS scales correlated very well with the functional and fatigue scores. CONCLUSIONS: We present a new instrument with moderate to high inter-observer agreement and adequate construct validity to measure PS in cancer patients. PMID- 26142727 TI - Potential DMSP-degrading Roseobacter clade dominates endosymbiotic microflora of Pyrodinium bahamense var. compressum (Dinophyceae) in vitro. AB - Many aspects of the biology and ecology of the toxic dinoflagellate Pyrodinium bahamense var. compressum are still poorly understood. In this brief note, we present identification of its associated intracellular bacteria or endosymbionts via PCR cloning and 16s rRNA gene sequencing and their localization by confocal microscopy, a first for Pyrodinium. The most frequently observed species in the endosymbiotic microflora were from Roseobacter clade (Alphaproteobacteria, 68%) and Gilvibacter sediminis (Flavobacteriaceae, 20%). Roseobacter lineage, the most abundant taxa in this study, is known to be involved in dimethylsulfoniopropionate metabolism which is highly produced in dinoflagellates a possible strong factor shaping the structure of the associated bacterial community. PMID- 26142728 TI - Investigation of the role of nitric oxide/soluble guanylyl cyclase pathway in ascorbic acid-mediated protection against acute kidney injury in rats. AB - The present study investigated the possible involvement of nitric oxide/soluble guanylyl cyclase (NO/sGC) pathway in ascorbic acid (AA)-mediated protection against acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia by occluding renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed in terms of measuring creatinine clearance (CrCl), blood urea nitrogen (BUN), plasma uric acid, potassium level, fractional excretion of sodium (FeNa), and microproteinuria. The NO level and oxidative stress in renal tissues were assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level. AA (50 and 100 mg/kg, p.o.) was administered for 3 days before subjecting rats to AKI. In separate groups, the nitric oxide synthase inhibitor, L-NAME (20 mg/kg, i.p.) and sGC inhibitor, methylene blue (50 mg/kg, i.p.) was administered prior to AA treatment in rats. The significant decrease in CrCl and increase in BUN, plasma uric acid, potassium, FeNa, microproteinuria, and oxidative stress in renal tissues demonstrated ischemia-reperfusion-induced AKI in rats. The AA treatment ameliorated ischemia-reperfusion-induced AKI along with the increase in renal NO level. The pretreatment with L-NAME and methylene blue abolished protective effect of AA. It is concluded that AA protects against ischemia-reperfusion-induced AKI. Moreover, the NO/sGC pathway finds its definite involvement in AA-mediated reno-protective effect. PMID- 26142729 TI - Test-retest repeatability of myocardial blood flow and infarct size using 11C acetate micro-PET imaging in mice. AB - PURPOSE: Global and regional responses of absolute myocardial blood flow index (iMBF) are used as surrogate markers to assess response to therapies in coronary artery disease. In this study, we assessed the test-retest repeatability of iMBF imaging, and the accuracy of infarct sizing in mice using (11)C-acetate PET. METHODS: (11)C-Acetate cardiac PET images were acquired in healthy controls, endothelial nitric oxide synthase (eNOS) knockout transgenic mice, and mice after myocardial infarction (MI) to estimate global and regional iMBF, and myocardial infarct size compared to (18)F-FDG PET and ex-vivo histology results. RESULTS: Global test-retest iMBF values had good coefficients of repeatability (CR) in healthy mice, eNOS knockout mice and normally perfused regions in MI mice (CR = 1.6, 2.0 and 1.5 mL/min/g, respectively). Infarct size measured on (11)C-acetate iMBF images was also repeatable (CR = 17 %) and showed a good correlation with the infarct sizes found on (18)F-FDG PET and histopathology (r (2) > 0.77; p < 0.05). CONCLUSION: (11)C-Acetate micro-PET assessment of iMBF and infarct size is repeatable and suitable for serial investigation of coronary artery disease progression and therapy. PMID- 26142730 TI - Long-term outcomes of (131)Iodine mIBG therapy in metastatic gastrointestinal pancreatic neuroendocrine tumours: single administration predicts non-responders. AB - BACKGROUND: (131)Iodine (I131)-metaiodobenzylguanidine (mIBG) is a radionuclide based treatment option for metastatic gastrointestinal-pancreatic neuroendocrine tumours (GEP NET). This study aimed at identifying prognostic indicators of long term outcome based on initial evaluation following a first mIBG treatment (7400 MBq) in a patient cohort with such tumours, with a secondary aim of evaluating progression-free survival (PFS) and overall survival (OS) following mIBG therapy. METHODS: Retrospective review of the hospital records was performed to identify a cohort of 38 adult patients who underwent (131)Iodine-mIBG therapy over a 9-year period for metastatic GEP NETs and neuroendocrine tumours with an unknown primary. Treatment response was evaluated based on radiological criteria (RECIST1.1), biochemical markers [serum Chromogranin A (CgA)/urinary 5HIAA] and symptomatic response at clinical follow-up, all evaluated at 3-6 months from first mIBG treatment. Progression-free survival (PFS) and overall survival (OS) from the first mIBG treatment were recorded. RESULTS: At 3-6 months following a single mIBG therapy, 75%, 67%, and 63% of patients showed either a partial response (PR) or stable disease (SD) on radiological, biochemical, and symptomatic criteria, respectively. Complete response (CR) was not seen in any patient. OS from the date of diagnosis and from the first therapy was 8 years +/ 1.1 (95% CI 5.7 to 10.2 years) and 4 years+/-0.69 (95% CI 2.6-5.3 years), respectively. Twenty-nine percent of patients were alive at 10 years. Significant survival advantage was seen in patients with SD/PR as compared to those who had progressive disease (PD) for each of these three criteria. CONCLUSION: Biochemical, radiological (RECIST 1.1) and symptomatic assessment of disease status at 3 to 6 months after first I131-mIBG therapy stratifies patients with a poor prognosis. This can be used to identify patients who may benefit from alternative strategies of treatment. PMID- 26142731 TI - Astroglial U87 Cells Protect Neuronal SH-SY5Y Cells from Indirect Effect of Radiation by Reducing DNA Damage and Inhibiting Fas Mediated Apoptotic Pathway in Coculture System. AB - Recent studies provide the evidence that indirect effects of radiation could lead to neuronal cells death but underlying mechanism is not completely understood. On the other hand astroglial cells are known to protect neuronal cells against stress conditions in vivo and invitro. Yet, the fate of neuronal cells and the neuroprotective effect of coculture system (with glial cells) in response to indirect radiation exposure remain rarely discussed. Here, we purpose that the indirect effect of radiation may induce DNA damage by cell cycle arrest and receptor mediated apoptotic cascade which lead to apoptotic death of neuronal SH SY5Y cells. We also hypothesized that coculture (with glial U87) may relieved the neuronal SH-SY5Y cells from toxicity of indirect effects radiation by reducing DNA damage and expression of apoptotic proteins in vitro. In the present study irradiated cell conditioned medium (ICCM) was used as source of indirect effect of radiation. Neuronal SH-SY5Y cells were exposed to ICCM with and without coculture with (glial U87) in transwell coculture system respectively. Various endpoints such as, cell survival number assay, Annexin V/PI assay, cell cycle analysis by flow cytometer, mRNA level of Fas receptor by q RT-PCR, expression of key apoptotic proteins by western blot and estimation of neurotrophic factors by ELISA method were analyzed into neuronal SH-SY5Y cells with and without co culture after ICCM exposure respectively. We found that ICCM induced DNA damage in neuronal SH-SY5Y cells by significant increase in cell cycle arrest at S-phase (***P < 0.001) which was further supported by over expression of P53 protein (**P < 0.01). While coculture (with glial U87), significantly reduced the ICCM induced cell cycle arrest and expression of P53 ((###) P < 0.001) neuronal SH-SY5Y cells. Further investigation of the underlying apoptotic mechanism revealed that in coculture system; ICCM induced elevated level of FAS mRNA level was significantly reduced ((###) P < 0.001) in neuronal SH-SY5Y cells which was followed by significant reduction in expression of key apoptotic protein i.e., FADD ((###) P < 0.001), caspase-8 ((###) P < 0.001), and cleaved caspase-3 ((###) P < 0.001) as compare to neuronal SH-SY5Y cells which received ICCM without coculture. Intriguingly, concentration of neurotrophic factors such as, GDNF and BDNF were significantly increased ((###) P < 0.001) in neuronal SH-SY5Y after coculture (with glial U87) cells. Hence, these findings infer that the receptor mediated pathway could be the one way through which indirect effects of radiation cause neurotoxicity. However, in co-cultures system (with glial U87) neuronal SH-SY5Y depicts remarkable resistance against ICCM induced neurotoxicity. PMID- 26142732 TI - Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion. AB - Hepatocellular carcinoma (HCC) is a major health concern with a high morbidity and mortality rate worldwide. However, the mechanism underlying hepatocarcinogenesis remains unclear. Forkhead box P2 (FOXP2) has been implicated in various human cancer types. However, the role of FOXP2 in HCC remains unknown. Western blot and immunohistochemistry were used to measure the expression of FOXP2 protein in HCC and adjacent normal tissues in 50 patients. Wound healing and transwell assays were used to determine the cell invasion ability. We showed that the level of FOXP2 was significantly reduced in HCC compared with the adjacent non-tumorous tissue. There was statistical significance between the expression of FOXP2 and vein invasion (P = 0.017), number of tumor nodes (P = 0.028), and AFP (P = 0.033). Low expression of FOXP2 correlated with poor survival. Moreover, wound healing and transwell assays showed that FOXP2 could decrease cell invasion and affect the expression of vimentin and E-cadherin. Our results suggested that FOXP2 expression was downregulated in HCC tumor tissues, and reduced FOXP2 expression was associated with poor overall survival. In addition, downregulation of FOXP2 significantly enhanced cell invasiveness. These findings uncover that FOXP2 might be a new prognostic factor and be closely correlated with HCC cell invasion. PMID- 26142734 TI - Mitochondrial targeted peptides for cancer therapy. AB - Mitochondria are a key pharmacological target in all cancer cells, since the structure and function of this organelle is different between healthy and malignant cells. Oxidative damage, disruption of mitochondrial ATP synthesis, calcium dyshomeostasis, mtDNA damage, and induction of the mitochondrial outer membrane permeabilization (MOMP) lead to the mitochondrial dysfunctionality and increase the probability of the programmed cell death or apoptosis. A variety of the signaling pathways have been developed to promote cell death including overexpression of pro-apoptotic members of Bcl-2 family, overloaded calcium, and elevated reactive oxygen species (ROS) play a key role in the promoting mitochondrial cytochrome c release through MOMP and eventually leads to cell death. There are a wide range of the therapeutic-based peptide drugs, known mitochondrial targeted peptides (MTPs), which specifically target mitochondrial pathways into death. They have prominent advantages such as low toxicity, high specificity, and easy to synthesis. Some of these therapeutic peptides have shown to increased the clinical activity alone or in combination with other agents. In this review, we will outline the biological properties of MTPs for cancer therapy. Understanding the molecular mechanisms and signaling pathways controlling cell death by MTPs can be critical for the development of the therapeutic strategies for cancer patients that would be valuable for researchers in both fields of molecular and clinical oncology. PMID- 26142733 TI - Folate-conjugated nanoparticles as a potent therapeutic approach in targeted cancer therapy. AB - The selective and efficient drug delivery to tumor cells can remarkably improve different cancer therapeutic approaches. There are several nanoparticles (NPs) which can act as a potent drug carrier for cancer therapy. However, the specific drug delivery to cancer cells is an important issue which should be considered before designing new NPs for in vivo application. It has been shown that cancer cells over-express folate receptor (FR) in order to improve their growth. As normal cells express a significantly lower levels of FR compared to tumor cells, it seems that folate molecules can be used as potent targeting moieties in different nanocarrier-based therapeutic approaches. Moreover, there is evidence which implies folate-conjugated NPs can selectively deliver anti-tumor drugs into cancer cells both in vitro and in vivo. In this review, we will discuss about the efficiency of different folate-conjugated NPs in cancer therapy. PMID- 26142735 TI - Temozolomide sensitizes stem-like cells of glioma spheres to TRAIL-induced apoptosis via upregulation of casitas B-lineage lymphoma (c-Cbl) protein. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has potent antitumor effects in glioma cell lines but has shown little clinical benefit for patients. We investigated whether the widely used chemotherapeutic agent temozolomide (TMZ) can sensitize glioma stem-like cells (GSCs) from human glioblastoma multiforme (GBM) to TRAIL-induced apoptosis. GSCs were isolated from GBM, and stem cell properties were confirmed by immunocytochemistry and in vivo tumorigenicity. Primary GSCs (PGCs) were produced by serum treatment of GBM derived cells. Changes in expression levels of various TRAIL-related signaling factors before and after TRAIL or TRAIL + TMZ treatment were measured by Western blotting. Overexpression vectors and siRNAs were used to investigate mechanism of TRAIL sensitivity. GSCs showed greater resistance to TRAIL-induced apoptosis than PGCs and had lower basal caspase activity. Caspase knockdown in PGCs reduced TRAIL sensitivity. Expression levels of c-Fas-associated death domain-like interleukin 1-converting enzyme-like inhibitory protein long and short isoforms (c-FLIPL and c-FLIPS) were significantly higher in GSCs than PGCs, and siRNA mediated c-FLIP knockdown in GSCs enhanced TRAIL-induced apoptosis. TMZ enhanced TRAIL-induced apoptosis in GSCs and downregulated c-FLIP expression. Add of TMZ also upregulated the expression of the E3 ubiquitin ligase casitas B-lineage lymphoma (c-Cbl). Moreover, overexpression of c-Cbl alone reduced c-FLIP expression, and c-Cbl knockdown both enhanced c-FLIP expression and reduced the potentiating effect of TMZ on TRAIL-induced apoptosis. The result indicated that TMZ may overcome TRAIL resistance in GSCs by suppressing c-FLIP expression through c-Cbl-mediated ubiquitination and degradation. PMID- 26142736 TI - Association between mismatch repair gene and irinotecan-based chemotherapy in metastatic colon cancer. AB - Mismatch repair (MMR) gene is closely related to the pathogenesis of colon cancer. This study aimed to evaluate the association between MMR status and efficacy of irinotecan-based chemotherapy. As a target of 5-FU, thymidylate synthase (TS) expression level might be influenced by irinotecan. Understanding whether this influence of TS is related with MMR status is helpful to the further exploration of the mechanism of irinotecan sensitivity in metastatic colon cancer with different MMR status. One hundred eighty-four patients with metastatic colon cancer receiving irinotecan-based chemotherapy for the first-line treatment were included. Correlations between MMR and clinicopathological characteristics and prognosis were determined. Two pairs of colon cancer cell lines (HCT-116 hMLH1(Vector) (deficient MMR, dMMR) versus HCT-116-hMLH1(+) (proficient MMR, pMMR); SW480-shRNA-hMLH1 (dMMR) versus SW480-shRNA-Control (pMMR)) were established by regulating MMR status. Sensitivity of these cell lines to irinotecan was determined by MTT assay. Regulation of TS by irinotecan was evaluated by western blotting and quantitative real-time PCR assay. dMMR accounted for 18.5 % and was related with proximal colon cancer (p = 0.005), poorly differentiated tumors (p = 0.018) and favorable efficacy with a higher disease control rate (DCR), a longer progression-free survival (PFS) and a trend of longer overall survival (OS). dMMR colon cancer cells were more sensitive to irinotecan. TS expression level was reduced more in dMMR cells after irinotecan treatment (p < 0.05). Our study favors an increased sensitivity of irinotecan in colon cancer with dMMR status. MMR status may be a predictive biomarker of response to irinotecan-based chemotherapy in metastatic colon cancer. PMID- 26142738 TI - In silico database screening of potential targets and pathways of compounds contained in plants used for psoriasis vulgaris. AB - Reviews and meta-analyses of clinical trials identified plants used as traditional medicines (TMs) that show promise for psoriasis. These include Rehmannia glutinosa, Camptotheca acuminata, Indigo naturalis and Salvia miltiorrhiza. Compounds contained in these TMs have shown activities of relevance to psoriasis in experimental models. To further investigate the likely mechanisms of action of the multiple compounds in these TMs, we undertook a computer-based in silico investigation of the proteins known to be regulated by these compounds and their associated biological pathways. The proteins reportedly regulated by compounds in these four TMs were identified using the HIT (Herbal Ingredients' Targets) database. The resultant data were entered into the PANTHER (Protein ANnotation THrough Evolutionary Relationship) database to identify the pathways in which the proteins could be involved. The study identified 237 compounds in the TMs and these retrieved 287 proteins from HIT. These proteins identified 59 pathways in PANTHER with most proteins being located in the Apoptosis, Angiogenesis, Inflammation mediated by chemokine and cytokine, Gonadotropin releasing hormone receptor, and/or Interleukin signaling pathways. All four TMs contained compounds that had regulating effects on Apoptosis regulator BAX, Apoptosis regulator Bcl-2, Caspase-3, Tumor necrosis factor (TNF) or Prostaglandin G/H synthase 2 (COX2). The main proteins and pathways are primarily related to inflammation, proliferation and angiogenesis which are all processes involved in psoriasis. Experimental studies have reported that certain compounds from these TMs can regulate the expression of proteins involved in each of these pathways. PMID- 26142737 TI - Specific upregulation of RHOA and RAC1 in cancer-associated fibroblasts found at primary tumor and lymph node metastatic sites in breast cancer. AB - The importance of tumor-stromal cell interactions in breast tumor progression and invasion is well established. Here, an evaluation of differential genomic profiles of carcinoma-associated fibroblasts (CAFs) compared to fibroblasts derived from tissues adjacent to fibroadenomas (NAFs) revealed altered focal adhesion pathways. These data were validated through confocal assays. To verify the possible role of fibroblasts in lymph node invasion, we constructed a tissue microarray consisting of primary breast cancer samples and corresponding lymph node metastasis and compared the expression of adhesion markers RhoA and Rac1 in fibroblasts located at these different locations. Two distinct tissue microarrays were constructed from the stromal component of 43 primary tumors and matched lymph node samples, respectively. Fibroblasts were characterized for their expression of alpha-smooth muscle actin (alpha-SMA) and vimentin. Moreover, we verified the level of these proteins in the stromal compartment from normal adjacent tissue and in non-compromised lymph nodes. Our immunohistochemistry revealed that 59 % of fibroblasts associated with primary tumors and 41 % of the respective metastatic lymph nodes (p = 0.271) displayed positive staining for RhoA. In line with this, 57.1 % of fibroblasts associated with primary tumors presented Rac1-positive staining, and the frequency of co-positivity within the lymph nodes was 42.9 % (p = 0.16). Expression of RhoA and Rac1 was absent in fibroblasts of adjacent normal tissue and in compromised lymph nodes. Based on our findings that no significant changes were observed between primary and metastatic lymph nodes, we suggest that fibroblasts are active participants in the invasion of cancer cells to lymph nodes and support the hypothesis that metastatic tumor cells continue to depend on their microenvironment. PMID- 26142739 TI - Predicting pleural invasion using HRCT and 18F-FDG PET/CT in lung adenocarcinoma with pleural contact. AB - OBJECTIVE: To evaluate the relevance of high-resolution computed tomography (HRCT) findings and fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake for risk stratification of visceral pleural invasion by lung adenocarcinoma. METHODS: The HRCT findings and (18)F-FDG uptake for lung adenocarcinomas with pleural contact on CT were retrospectively analyzed in 208 consecutive patients (94 females and 114 males; median age, 69.0 years) between January 2009 and December 2013, with institutional review board approval. The HRCT findings and maximum standardized uptake value (SUV max) were recorded for each patient. Multivariate logistic regression was used for statistical analysis, and subgroup analysis stratified for whole tumor size <= 3 cm was also performed. RESULTS: Multivariate analysis showed that SUV max [odds ratio (OR) 1.09, 95 % confidence interval (CI) 1.02 1.16, P = 0.014] and obtuse angle (OR 4.14, 95 % CI 1.97-8.74, P < 0.001) were significant independent predictors for visceral pleural invasion. Receiver operating characteristic (ROC) analysis showed that, compared with the multivariate models [area under the curve (Az) 0.819-0.829], SUV max alone (Az 0.815) was useful in predicting visceral pleural invasion. In the subgroup analysis, multivariate analysis showed that SUV max (OR 1.29, 95 % CI 1.12-1.50, P = 0.001) and contact length with the pleura (OR 1.13, 95 % CI 1.05-1.22, P = 0.001) were significant independent predictors for visceral pleural invasion. ROC analysis showed that SUV max alone (Az 0.844) showed similar diagnostic performance to the multivariate models (Az 0.845-0.857). CONCLUSIONS: SUV max alone and multivariate models including SUV max are useful for the prediction of visceral pleural invasion by lung adenocarcinoma. PMID- 26142742 TI - Enabling Ethical Code Embeddedness in Construction Organizations: A Review of Process Assessment Approach. AB - Several researchers have identified codes of ethics (CoEs) as tools that stimulate positive ethical behavior by shaping the organisational decision-making process, but few have considered the information needed for code implementation. Beyond being a legal and moral responsibility, ethical behavior needs to become an organisational priority, which requires an alignment process that integrates employee behavior with the organisation's ethical standards. This paper discusses processes for the responsible implementation of CoEs based on an extensive review of the literature. The internationally recognized European Foundation for Quality Management Excellence Model (EFQM model) is proposed as a suitable framework for assessing an organisation's ethical performance, including CoE embeddedness. The findings presented herein have both practical and research implications. They will encourage construction practitioners to shift their attention from ethical policies to possible enablers of CoE implementation and serve as a foundation for further research on ethical performance evaluation using the EFQM model. This is the first paper to discuss the model's use in the context of ethics in construction practice. PMID- 26142741 TI - Low levels of circulating platelet factor 4 (PF4, CXCL4) in subclinically hypothyroid autoimmune thyroiditis. AB - PURPOSE: Chemokines play an important role in the pathogenesis of autoimmune thyroid diseases. Platelet factor 4 (PF4, CXCL4) released from activated platelets is a chemokine. However, its clinical importance in autoimmune thyroiditis remains unknown. This study is intended to determine circulating levels of PF4 levels in patients with autoimmune thyroiditis (AIT). METHODS: Circulating levels of PF4 were measured in 34 consecutive patients with newly diagnosed AIT and 18 euthyroid controls. Among AIT group, 16 patients were euthyroid and 18 had subclinic hypothyroidism. Controls and individuals with AIT were similar in terms of age. RESULTS: Serum levels of PF4 were comparable in patients with AIT and in controls. Among patients with AIT, PF4 was significantly lower in those with subclinical hypothyroidism than in euthyroid individuals (p = 0.001). In correlation analysis, PF4 was negatively correlated with TSH (r = 0.663, p = 0.000) and positively correlated with free T4 (r = 0.428, p = 0.012). There was not any significant correlation between PF4 and AbTPO, AbTg. CONCLUSION: The present study demonstrated for the first time that circulating PF4 levels are decreased in subclinically hypothyroid AIT. This result draws attention to the circulating PF4 levels in subclinically hypothyroid AIT and may shed light on further researches at this topic. PMID- 26142740 TI - Everything you ever wanted to know about phosphodiesterase 5 inhibitors and the heart (but never dared ask): How do they work? AB - INTRODUCTION: Phosphodiesterase 5 inhibitors (PDE5i) were developed while investigating novel treatments for coronary artery disease, but their andrological side effects shifted their indication toward the management of erectile dysfunction. Although PDE5i are now also indicated for pulmonary arterial hypertension and there are mounting preclinical and clinical evidences about their potentially beneficial cardiac effects, their use remains controversial and the involved mechanisms remain unclear. MATERIALS AND METHODS: This review aimed to analyze the effects of PDE5i administration in various animal and humans models of cardiovascular diseases. RESULTS: Animal studies have shown that PDE5i have protective effects in several models of cardiac disease. In humans, some studies showed that PDE5i improves microvascular and endothelial dysfunction and exerts positive effects in different samples of cardiovascular (CV) impairment. In contrast, other studies found no benefit (and no harm) in heart failure with preserved ejection fraction. The discrepancies in these findings are likely related to the fact that the mechanisms targeted by PDE5i in human disease are still poorly understood and the target population not yet identified. The mechanisms of actions herein reviewed suggest that hypertrophy, microvascular impairment, and inflammation, should be variably present for PDE5i to work. All these conditions frequently coexist in diabetes. A gender responsiveness has also been recently proposed. CONCLUSIONS: Continuous PDE5 inhibition may exert cardioprotective effects, improving endothelial function and counteracting cardiac remodeling in some but not all conditions. A better patient selection could help to clarify the controversies on PDE5i use for CV disorders. PMID- 26142743 TI - Provision of evidence-based intervention is not part of the DSM-5 diagnostic criteria for Specific Learning Disorder. PMID- 26142745 TI - Application of HPLC to assess the compatibility of bisoprolol fumarate with selected excipients in mixtures by isothermal stress testing. AB - In the present study, the compatibility between bisoprolol fumarate and selected excipients (ascorbic acid, citric acid anhydrous, butylated hydroxyanisole, polyvinylpyrrolidone, glycerol, mannitol and sorbitol) in mixtures (1:10 ratio of drug and excipient) was investigated by subjecting the samples to isothermal stress conditions (90 degrees C for 48 h). A new HPLC method was developed, validated and employed for determining the drug content of the stressed compatibility samples. Results of HPLC revealed that major degradation of bisoprolol fumarate was observed with butylated hydroxyanisole (89.4%), citric acid anhydrous (89%), mannitol (77%) and glycerol (61.9%). PMID- 26142744 TI - Premature aging of the hippocampal neurogenic niche in adult Bmal1-deficient mice. AB - Hippocampal neurogenesis undergoes dramatic age-related changes. Mice with targeted deletion of the clock geneBmal1 (Bmal1(-/-)) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1(-/-) mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1(-/-) mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70 kDa and expression of the cell cycle inhibitor p21(Waf1/CIP1) were increased in adult Bmal1(-/-) mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age-dependent decline in adult neurogenesis presumably as a consequence of oxidative stress. PMID- 26142746 TI - Fullerenes(nC60) affect the growth and development of the sediment-dwelling invertebrate Chironomus riparius larvae. AB - The possible toxicity of nanoparticles (NPs) to aquatic organisms needs to be investigated for chronic effects at low concentrations. Chronic effects of carbon NPs, fullerenesC60, on the midges of Chironomus riparius at different life stages on larvae and adult midges were investigated. Sediment associated fullerenesC60 were studied by 10-day growth and 42-day emergence tests with artificial sediment at nominal concentration ranges 0.0004-80 mg/kg dry weight. The body length decreased in the lower tested concentrations (0.0025-20 mg/kg), but the effect vanished with higher concentrations. Delayed emergence rate observed at 0.5 mg/kg. The observed effects correlated with analyzed sediment particle sizes indicating that small agglomerates of fullerene have more significant effects on C. riparius than larger agglomerates observed with higher C60 doses. The results reveal that fullerene may pose risks to benthic organisms, emerging as changes in the ecotoxic parameters studied here which inflects by the survival of the population. PMID- 26142747 TI - Characterization and phthalate esters sorption of organic matter fractions isolated from soils and sediments. AB - The sorption of two phthalate esters (PAEs) and phenanthrene (PHE) by different natural organic matter fractions (NOMs) was examined. The surface area of the NOMs correlated positively with the starting decomposition temperature (SDT), implying increased number of micropores with the rise of condensation. Sorption of PHE on nonhydrolyzable carbons (NHCs) and other NOMs was respectively dependent on aromatic and aliphatic C contents. Likely physical blocking of the aliphatic moieties and input of black carbon materials led to elevated sorption capacity for PHE of aromatic domains in the NHCs. Sorption of PAEs by NOMs excluding NHCs was jointly regulated by hydrophobic partitioning and H-bonding interactions. The SDT of the NOMs correlated negatively with the Koc when SDT >=304 degrees C, likely because the highly condensed domains may impair the availability of amorphous moieties for sorption. This study highlights the influence of domain accessibility of NOMs on sorption of hydrophobic organic contaminants. PMID- 26142748 TI - Prenatal exposure to polybrominated diphenyl ethers and birth outcomes. AB - This study aimed to examine the potential association between maternal PBDEs and birth outcomes, including birth weight (g), length (cm), head circumference (cm) and gestational age (week). 215 mothers were recruited from a prospective birth cohort in rural northern China between September 2010 and February 2012. Serum PBDE congeners were detected and their association with birth outcomes were examined. The median maternal serum concentrations of BDE-28, -47, -99, -100, 153 were 2.27, 2.26, 3.58, 2.13, 4.87 ng/g lipid, respectively. Maternal LgBDE-28 and LgBDE-100 were negatively associated with birth length (beta = -0.92, 95% confidence interval (CI): -1.82, -0.02; beta = -0.97, 95% CI: -1.83, -0.08). A negative association was found between LgBDE-28 and birth weight among male infants (beta = -253.76, 95% CI: -438.16, -69.36). PBDE congeners were not associated with head circumference, or gestational age. Our results contribute to growing evidence suggesting that PBDEs have adverse effects on birth outcomes. PMID- 26142749 TI - Distribution of persistent organic pollutants (PAHs, Me-PAHs, PCBs) in dissolved, particulate and sedimentary phases in freshwater systems. AB - The occurrence of three groups of hazardous organic contaminants (PCBs, PAHs, Me PAHs) in fifteen watercourses and rivers located in highly urbanized and industrialized zones was studied. The distribution of 62 organic contaminants was determined in three matrices: in the dissolved phase, associated with suspended solid matter (SSM) and in sediment. Their distributions in the aquatic environment depend strongly on their physicochemical properties. Low molecular weight PAHs were predominant in the dissolved phase while those with high molecular weight accumulated preferentially in SSM and sediments. Among the 28 PCBs congeners, only PCB153 was detected. The results showed that the contamination of these areas originated mainly from combustion processes. The three the most polluted sites identified are surrounded by big cities. Ecotoxicological assessment based on the international Sediment Quality Guidelines (SQGs) showed that the toxic effects of the sediment in these watercourses and rivers occurred due to high levels of hydrocarbons. PMID- 26142750 TI - Uptake of antimonite and antimonate by arsenic hyperaccumulator Pteris vittata: Effects of chemical analogs and transporter inhibitor. AB - Antimonite (SbIII) is transported into plants via aquaglyceroporin channels but it is unknown in As-hyperaccumulator Ptreis vittata (PV). We tested the effects of SbIII analogs (arsenite-AsIII, glycerol, silicic acid-Si, and, glucose), antimonate (SbV) analog (phosphate-P), and aquaglyceroporin transporter inhibitor (silver, Ag) on the uptake of SbIII or SbV by PV gametophytes. PV gametophytes were grown in 20% Hoagland solution containing 65 MUM SbIII or SbV and increasing concentrations of analogs at 65-6500 MUM for 2 h or 4 h under sterile condition. After exposing to 65 MUM Sb for 2 h, PV accumulated 767 mg/kg Sb in SbIII treatment and 419 mg/kg in SbV treatment. SbIII uptake by PV gametophytes was not impacted by glycerol or AsIII nor aquaglyceroporin inhibitor Ag during 2 h exposure. While Si increased SbIII uptake and glucose decreased SbIII uptake by PV gametophytes, the impact disappeared during 4 h exposure. Under P-sufficient condition, P increased SbIII uptake and decreased SbV uptake during 2 h exposure, but the effect again disappeared after 4 h. After being P-starved for 2 weeks, P decreased SbIII with no effect on SbV uptake during 2 h exposure. Our results indicated that: 1) PV gametophytes could serve as an efficient model to study Sb uptake, and 2) unique SbIII uptake by PV may be related to its trait of As hyperaccumulation. PMID- 26142751 TI - Evolved pesticide tolerance in amphibians: Predicting mechanisms based on pesticide novelty and mode of action. AB - We examined 10 wood frog populations distributed along an agricultural gradient for their tolerance to six pesticides (carbaryl, malathion, cypermethrin, permethrin, imidacloprid, and thiamethoxam) that differed in date of first registration (pesticide novelty) and mode-of-action (MOA). Our goals were to assess whether: 1) tolerance was correlated with distance to agriculture for each pesticide, 2) pesticide novelty predicted the likelihood of evolved tolerance, and 3) populations display cross-tolerance between pesticides that share and differ in MOA. Wood frog populations located close to agriculture were more tolerant to carbaryl and malathion than populations far from agriculture. Moreover, the strength of the relationship between distance to agriculture and tolerance was stronger for older pesticides compared to newer pesticides. Finally, we found evidence for cross-tolerance between carbaryl and malathion (two pesticides that share MOA). This study provides one of the most comprehensive approaches for understanding patterns of evolved tolerance in non pest species. PMID- 26142752 TI - Simultaneous assessments of occurrence, ecological, human health, and organoleptic hazards for 77 VOCs in typical drinking water sources from 5 major river basins, China. AB - Owing to the growing public awareness on the safety and aesthetics in water sources, more attention has been given to the adverse effects of volatile organic compounds (VOCs) on aquatic organisms and human beings. In this study, 77 target VOCs (including 54 common VOCs, 13 carbonyl compounds, and 10 taste and odor compounds) were detected in typical drinking water sources from 5 major river basins (the Yangtze, the Huaihe, the Yellow, the Haihe and the Liaohe River basins) and their occurrences were characterized. The ecological, human health, and olfactory assessments were performed to assess the major hazards in source water. The investigation showed that there existed potential ecological risks (1.30 * 10 <= RQtotals <= 8.99 * 10) but little human health risks (6.84 * 10(-7) <= RQtotals <= 4.24 * 10(-4)) by VOCs, while that odor problems occurred extensively. The priority contaminants in drinking water sources of China were also listed based on the present assessment criteria. PMID- 26142753 TI - Influence of polyethylene microplastic beads on the uptake and localization of silver in zebrafish (Danio rerio). AB - This study aimed to determine whether the uptake and localization of Ag in zebrafish was affected by the presence of polyethylene microplastic beads (PE MPBs). Zebrafish were exposed to 1 MUg Ag L(-1) (radiolabelled with (110m)Ag) for 4 and 24 h in the presence or absence of PE MPBs (10, 100 or 1000 MPBs mL(-1)), and one treatment in which MPBs (1000 MPBs mL(-1)) were incubated with Ag to promote adsorption. The presence of MPBs, at any of the tested doses, had no effect on the uptake or localization of Ag. However, exposure to the Ag-incubated MPBs (?75% of the Ag bound to MPBs) significantly reduced Ag uptake at both time points and also significantly increased the proportion of intestinal Ag. This study demonstrates that microplastics can alter the bioavailability and uptake route of a metal contaminant in a model fish species. PMID- 26142754 TI - Fate and transport of free and conjugated estrogens during soil passage. AB - Endocrine disrupting chemicals, such as the free estrogens 17beta-estradiol (E2), estrone (E1) and the conjugated estrogen estrone-sulfate (E1-3S) are found at low concentration levels in the environment. This is somehow contradictory to the strong sorption and high degradation potentials found in laboratory experiments. In particular, the fate and transport behavior of conjugated estrogens is poorly understood, and the importance of enzymes triggering the transformation pathways has received little attention. To address these deficiencies, the present research uses packed laboratory soil columns with pulse injections of free estrogens, either E2 or E1, or E1-3S, to provide sound evidence of the transformation pathways. It is further shown that (i) transport of free estrogens is subject to strong retardation and degradation, (ii) the transport of conjugated estrogens is less retarded and only to a minor degree affected by degradation, and (iii) arylsulfotransferase is the enzyme triggering the transformation reaction. PMID- 26142755 TI - The deal with diel: Temperature fluctuations, asymmetrical warming, and ubiquitous metals contaminants. AB - Climate projections over the next century include disproportionately warmer nighttime temperatures ("asymmetrical warming"). Cool nighttime temperatures lower metabolic rates of aquatic ectotherms. In contaminated waters, areas with cool nights may provide thermal refugia from high rates of daytime contaminant uptake. We exposed Cope's gray tree frogs (Hyla chrysoscelis), southern leopard frogs (Lithobates sphenocephalus), and spotted salamanders (Ambystoma maculatum) to five concentrations of a mixture of cadmium, copper, and lead under three to four temperature regimes, representing asymmetrical warming. At concentrations with intermediate toxicosis at test termination (96 h), temperature effects on acute toxicity or escape distance were evident in all study species. Asymmetrical warming (day:night, 22:20 degrees C; 22:22 degrees C) doubled or tripled mortality relative to overall cooler temperatures (20:20 degrees C) or cool nights (22:18 degrees C). Escape distances were 40-70% shorter under asymmetrical warming. Results suggest potentially grave ecological impacts from unexpected toxicosis under climate change. PMID- 26142756 TI - The role of arginine vasopressin in electroacupuncture treatment of primary sciatica in human. AB - It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5 +/- 2.5 pg/ml), not plasma (13.2 +/- 4.2 pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1 +/- 3.8 pg/ml and 12.3 +/- 3.4 pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral "Zusanli" points (St. 36) for 60 min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients. PMID- 26142757 TI - Effect of carnosine, methylprednisolone and their combined application on irisin levels in the plasma and brain of rats with acute spinal cord injury. AB - Spinal cord injury (SCI) might occur to anybody at any time and any age. In its treatment, methylprednisolone (MP) is a first choice worldwide, but there is still no significant breakthrough in truly beneficial treatment due to SCI's complex pathophysiology. We investigated the effect of carnosine, methylprednisolone (MP) and its combination on irisin levels in the plasma, brain and medulla spinalis tissues in SCI using a rat model. The rats were divided into 6 groups: I (Control, saline); II (sham animals with laminectomy without cross clamping); III (SCI); IV (SCI treated with 150mg/kg carnosine); V (SCI treated with 30mg/kg methylprednisolone); and VI (SCI treated with a combination of carnosine and MP). The animals were given traumatic SCI after laminectomy, using 70-g closing force aneurysm clips (Yasargil FE 721). Irisin concentration was measured by ELISA. The distribution of irisin in brain and spinal cord tissues was examined by immunochemistry. Irisin was mainly expressed in the astrocytes and microglia of brain tissues, and multipolar neurones of the anterior horn of spinal cord tissue in rats of all groups, indicating that irisin is physiologically indispensable. MP and carnosine and the combination of the two, significantly increased irisin in plasma and were accompanied by a significant rise in irisin immunoreactivity of brain and spinal cord tissues of the injured rats compared with control and sham. This finding raises the possibility that methylprednisolone and carnosine regulate the brain and spinal cord tissues in SCI by inducing irisin expression, and may therefore offer a better neurological prognosis. PMID- 26142758 TI - Computational assignment of cell-cycle stage from single-cell transcriptome data. AB - The transcriptome of single cells can reveal important information about cellular states and heterogeneity within populations of cells. Recently, single-cell RNA sequencing has facilitated expression profiling of large numbers of single cells in parallel. To fully exploit these data, it is critical that suitable computational approaches are developed. One key challenge, especially pertinent when considering dividing populations of cells, is to understand the cell-cycle stage of each captured cell. Here we describe and compare five established supervised machine learning methods and a custom-built predictor for allocating cells to their cell-cycle stage on the basis of their transcriptome. In particular, we assess the impact of different normalisation strategies and the usage of prior knowledge on the predictive power of the classifiers. We tested the methods on previously published datasets and found that a PCA-based approach and the custom predictor performed best. Moreover, our analysis shows that the performance depends strongly on normalisation and the usage of prior knowledge. Only by leveraging prior knowledge in form of cell-cycle annotated genes and by preprocessing the data using a rank-based normalisation, is it possible to robustly capture the transcriptional cell-cycle signature across different cell types, organisms and experimental protocols. PMID- 26142759 TI - RNA-protein interaction methods to study viral IRES elements. AB - Translation control often takes place through the mRNA untranslated regions, involving direct interactions with RNA-binding proteins (RBPs). Internal ribosome entry site elements (IRESs) are cis-acting RNA regions that promote translation initiation using a cap-independent mechanism. A subset of positive-strand RNA viruses harbor IRESs as a strategy to ensure efficient viral protein synthesis. IRESs are organized in modular structural domains with a division of functions. However, viral IRESs vary in nucleotide sequence, secondary RNA structure, and transacting factor requirements. Therefore, in-depth studies are needed to understand how distinct types of viral IRESs perform their function. In this review we describe methods to isolate and identify RNA-binding proteins important for IRES activity, and to study the impact of RNA structure and RNA-protein interactions on IRES activity. PMID- 26142760 TI - Behavioral Dysphonia and Depression in Elementary School Teachers. AB - OBJECTIVE/HYPOTHESIS: To verify the relationship between behavioral dysphonia and current depressive episodes in municipal elementary school teachers. We hypothesize that teachers with behavioral dysphonia will be more susceptible to psychiatric disorders. DESIGN: Cross-sectional study, quantitative, conducted across municipal schools in both rural and urban regions of Pelotas. METHOD: Five hundred seventy-five teachers from urban and rural areas of the same Brazilian state were included. The full version of the Voice Handicap Index validated into Brazilian Portuguese was used to determine the presence of behavioral dysphonia. A profile of vocal behaviors was also used to quantify the number of phonotraumatic events. In addition, the Mini-International Neuropsychiatric Interview was used to determine current episodes of depression. Data were analyzed via correlative studies using chi-square and Poisson regression analyses. RESULTS: Across all teachers, the prevalence of dysphonia was 33.9% and 55% reported that they had already taken a leave because of their voice. Those teachers with a current depressive episode had a higher rate of dysphonia compared with those without depression (prevalence ratio [PR] 1.66; P < 0.000). Teachers who presented with a risk of serious vocal problems had a prevalence ratio of 2.58, indicating a greater proportion of dysphonia, whereas teachers classified as champions of abuse were five times more likely compared with those teachers with behaved or candidates for voice problems. CONCLUSIONS: There is an association between behavioral dysphonia and current depressive episodes in elementary school teachers. PMID- 26142761 TI - [Brody syndrome: an underdiagnosed cause of muscle stiffness and cramps in children]. PMID- 26142762 TI - [Research activity during residency in pediatrics: an opportunity for early publication]. PMID- 26142763 TI - [Fortuitously discovered neutropenia in children: diagnosis and follow-up]. AB - Neutropenia seems to be quite frequent in current pediatric practice and can confuse the clinician since it may result from a severe cause. The aim of this study was to provide a prospective description of episodes of neutropenia in children to assess its clinical relevance in a general pediatric cohort consulting and/or hospitalized in a French university hospital. In this prospective observational and monocentric study conducted from April 2012 to April 2013, we included all the patients under 18 years of age who presented neutropenia (defined as an absolute neutrophil count [ANC] below 1*10(9)/L before 1 year of age and below 1.5*10(9)/L beyond) on a whole blood count (WBC) performed in our hospital. Patients treated with chemotherapy were not included. Medical records were regularly checked for at least 1 year after inclusion, and clinical and biological data were collected prospectively to compare transient episodes of neutropenia (<3 months) with persistent episodes of neutropenia (>3months). Of 55,018 consultations and 13,967 hospitalizations (chemotherapy excluded), 8966 blood counts were performed and 250 episodes of neutropenia were found in 238 patients. Data concerning clinical progression were available in 195 cases of which 136 had at least one subsequent WBC. Two hundred thirty-one episodes corresponded to new episodes, while neutropenia preexisted before inclusion in the others. The median follow-up was 12.8 months. Most episodes of neutropenia occurred in children <2 years of age (52%), with a median age of 22.2 months. Mean ANC was 0.943*10(9)/L (+/-0.340) and a few episodes of neutropenia were below 0.5*10(9)/L (9.2%). Neutropenia persisted more than 3 months in only 13.2% of cases. When neutropenia was below 0.5*10(9)/L, it significantly persisted (RR=3.08; 95% CI [1.31-7.22]). Other factors associated with persistent neutropenia were thrombocytopenia, monocytopenia, a CRP more than 70mg/L, significant abnormality on the clinical exam, and age over 24 months. However, multivariate analysis showed that only an ANC below 0.5*10(9)/L was significantly associated with persistence. While etiology could not be determined in 32% of cases, neutropenia resulted mostly from infectious causes (37.8%), with other causes being more anecdotal. The majority of infectious episodes of neutropenia were viral (90.3%). Like other studies, this investigation suggests that most episodes of neutropenia concern young children, are transient, are benign and often due to infectious diseases. Although it may not reflect the medullar stock or the real capacity of neutrophils to fight bacterial infections, it seems that neutropenia below 0.5*10(9)/L is more likely to persist and be complicated, as previous studies also suggest. To conclude, neutropenia is not exceptional in children and, even if it often results from viral infections and mostly evolves favorably, the clinician should closely monitor these patients, especially when neutrophils are below 0.5*10(9)/L. PMID- 26142765 TI - Ductal closure and near-infrared spectroscopy for regional oxygenation monitoring in ductus-dependent congenital heart disease. AB - In ductus-dependent congenital heart disease, preserving the blood flow through the ductus arteriosus (DA) is vital before surgery. We present the cases of three full-term neonates with ductus-dependent congenital heart disease for whom near infrared spectroscopy (NIRS) monitoring was performed. We recorded cyclical drops in regional oxygen saturation, both cerebral and renal, that corresponded to constrictions of the DA. These findings appeared either simultaneously or previous to SpO2 drops and were corrected by prostaglandin infusion. Through these cases, we assume that cyclical constrictions of ductal cells participate in the DA closure process in its early phase. PMID- 26142764 TI - [Epidemiology of malformations associated with cleft lip and palate: a retrospective study of 324 cases]. AB - PURPOSE: Children with cleft lip and/or palate may have associated malformations, whether or not they are included in a syndromic form. This study's purpose was to provide a better understanding of the epidemiology and distribution of malformations and syndromes associated with these clefts. METHODS: Retrospective study of 324 patients with cleft lip or palate born between 1994 and 2011. The associated malformations were diagnosed during the 1st year of life. RESULTS: Cleft lip or labioalveolar clefts were less frequently associated with other malformations than cleft palate. These nonsyndromic malformations preferentially affected the urogenital and renal system in case of cleft palate (48.5%) and the cardiovascular system for clefts with a lip defect (30.5%). The syndromic forms were rare in the cleft lip and labioalveolar clefts (3.47%). In contrast, cleft palate appeared much more frequently included in a syndromic form, with 52 children out of 151 (34.4%). The Pierre-Robin sequence was the most frequent syndrome with more than 25% of the cleft palate population. The defect of the palate was associated with a higher rate of other malformations or syndromes (36.51% vs 29.9% for the entire population with a cleft) (n=324) (P<0.001). CONCLUSIONS: The distribution of malformations appears to be linked to the type of cleft. These findings underline the importance of conducting a systematic neonatal malformation workup in children born with clefts in order to diagnose abnormalities and organize effective and consistent management. PMID- 26142766 TI - [Impact on the healthcare team and parents of the type of cardiorespiratory monitoring during phototherapy]. AB - INTRODUCTION: Neonatal jaundice is treated with phototherapy and requires continuous cardiorespiratory monitoring, which can induce parental anxiety. Within a very short time, parents receive the announcement of the diagnosis and of the need for a treatment in another unit with a new team of caregivers. OBJECTIVE: To evaluate parents' anxiety and their feelings concerning the location of treatment concerning cardiorespiratory monitoring equipment (wired vs Wi-Fi wireless monitoring equipment) and treatment location (neonatology vs maternity wards) during a phototherapy treatment in the neonatology unit, located in the maternity wards. METHODS: This was a prospective and monocentric study. Parental anxiety was assessed using the STAI-Y score. Their feelings on the location of treatment were assessed using a specific questionnaire. Three successive periods were considered: period I "wired with neonatology team," period II "Wi-Fi with neonatology team," and period III "Wi-Fi with maternity wards". Comparison between periods I and II evaluated the impact of the monitoring equipment and comparison between periods II and III assessed the impact of the treatment location. RESULTS: No effects of the monitoring equipment were observed. We found an impact of the treatment location in charge of the newborn: the parent's anxiety (STAI-Y score) was lower in the maternity wards, whereas the maternity ward personnel considered the protocol as an increased workload (p<0.001). CONCLUSION: The monitoring equipment had little effect. Parental anxiety decreased when monitoring took place in the usual maternity wards, underscoring the advantages of a close relationship between maternity and neonatology units. PMID- 26142767 TI - [Statins for children with hypercholesterolemia]. AB - In the different types of children's hypercholesterolemia, some severe inherited monogenic forms, transmitted as a dominant trait, carry a high risk of early cardiovascular events in young adults and a decrease in life expectancy, warranting the initiation of a preventive cholesterol-lowering treatment early in childhood. As in adult patients, statins are the first-line drugs. The purpose of this article is to review the existing recommendations for their indications in children, their benefits, their tolerance, as well as their prescription and monitoring modalities. PMID- 26142768 TI - [Silence would be the greatest error]. PMID- 26142769 TI - [Encephalitis in a 12-year-old boy]. PMID- 26142770 TI - [Thymoma in children: a rare and difficult diagnosis]. AB - Thymoma is extremely rare within the pediatric age range, which could lead to delayed diagnosis. Based on the clinical case of a mediastinal tumor in an 8-year old patient, we detail the key points in the management of this disease highlighted by our recent experience. PMID- 26142771 TI - [Nicotine poisoning from patch application: a pediatric case report]. PMID- 26142772 TI - [Inhaled corticosteroids and growth: should we be worried?]. AB - Inhaled corticosteroids (ICSs) are the cornerstone and the first stage of asthma treatment. The objective of this study was to synthesize data on the potential effects of ICSs on growth in children. Studies on the short-term impact of ICSs on growth evaluated by knemometry cannot be extrapolated to the medium or long term and therefore have no utility in real life for a given person. In the medium term, the various ICSs given at the usual doses cause a small reduction in growth after 6 months of treatment. This slowdown occurs at the beginning of treatment, especially in younger children, and the growth velocity corrects itself later but without catching up. In the long term, the prolonged use of ICSs seems to induce a small reduction in the final size in adulthood (close to 1cm) occurring in the first 2 years of treatment without worsening over time. The impact of gender, age at onset of treatment, different ICSs, modes of inhalation, and severity of asthma should also be studied further. The benefit of ICSs in asthma treatment is greater than the risk of side effects, including on growth. The majority of the therapeutic effect is obtained for small to moderate doses of ICSs. Regular adjustment of ICS dose for optimal asthma control should also reduce ICS dose and the impact on growth. PMID- 26142774 TI - Using the morphology of the hominoid distal fibula to interpret arboreality in Australopithecus afarensis. AB - The fibula has rarely been considered in anthropological studies. However differences in morphology - and inferred function - of the fibula between human and non-human apes have been noted in the past and related to differences in locomotor behavior. Recent studies have pointed out the correlation between diaphyseal rigidity of the fibula and tibia and locomotor behavior in living hominids, and its possible application for inferring early hominin locomotor behavior. The problem with the application of the method proposed in these studies is the extreme rarity of associated early hominin fibula and tibia. Additionally, previous studies investigating morphological traits of fibulotalar articular facets to infer the degree of arboreality in fossil australopiths were often qualitative. In the present study, articular measurements of the distal fibula of living great apes and humans (Pongo, Gorilla, Pan and Homo) are quantified and compared to Australopithecus afarensis distal fibulae. Quantitative analysis is carried out for articular areas and breadths of the fibulotalar articular facets, for the angles formed by the fibulotalar articular facets and the longitudinal axis of the fibula, and for the angle between the proximal fibulotalar articular facet and the subcutaneous triangular area. Results show that the fibula of A. afarensis bears some traits consistent with modern terrestrial bipedalism, like a more laterally facing lateral malleolus, in association with more ape-like traits, like the smaller distal fibulotalar articular facet area and the more inferiorly oriented fibulotalar articular facets, consistent with A. afarensis being a terrestrial hominin adapted for some form of arboreality. PMID- 26142775 TI - A smart polymeric platform for multistage nucleus-targeted anticancer drug delivery. AB - Tumor cell nucleus-targeted delivery of antitumor agents is of great interest in cancer therapy, since the nucleus is one of the most frequent targets of drug action. Here we report a smart polymeric conjugate platform, which utilizes stimulus-responsive strategies to achieve multistage nuclear drug delivery upon systemic administration. The conjugates composed of a backbone based on N-(2 hydroxypropyl) methacrylamide (HPMA) copolymer and detachable nucleus transport sub-units that sensitive to lysosomal enzyme. The sub-units possess a biforked structure with one end conjugated with the model drug, H1 peptide, and the other end conjugated with a novel pH-responsive targeting peptide (R8NLS) that combining the strength of cell penetrating peptide and nuclear localization sequence. The conjugates exhibited prolonged circulation time and excellent tumor homing ability. And the activation of R8NLS in acidic tumor microenvironment facilitated tissue penetration and cellular internalization. Once internalized into the cell, the sub-units were unleashed for nuclear transport through nuclear pore complex. The unique features resulted in 50-fold increase of nuclear drug accumulation relative to the original polymer-drug conjugates in vitro, and excellent in vivo nuclear drug delivery efficiency. Our report provides a strategy in systemic nuclear drug delivery by combining the microenvironment responsive structure and detachable sub-units. PMID- 26142773 TI - K-Cl cotransporters, cell volume homeostasis, and neurological disease. AB - K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1 related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. PMID- 26142776 TI - Mitophagy induced by nanoparticle-peptide conjugates enabling an alternative intracellular trafficking route. AB - The intracellular behaviors of nanoparticles are fundamentally important for the evaluation of their biosafety and the designs of nano carrier-assisted drug delivery with high therapeutic efficacy. It is still in a great need to discover how functionalized nanoparticles are transported inside the cells, for instance, in a complicated fashion of translocation between different types of cell organelles. Here we report a new understanding of the interactions between nanoparticles and cells by the development of polyoxometalates nanoparticle peptide conjugates and investigation of their intracellular trafficking behaviors. The as-prepared nanoparticles are featured with a unique combination of fluorescence and high contrast for synchrotron X-ray-based imaging. Functional surface modification with peptides facilitates effective delivery of the nanoparticles onto the target organelle (mitochondria) and subsequent intracellular trafficking in a dynamic mode. Interestingly, our experimental results have revealed that autophagy of mitochondria (mitophagy) can be induced by NP-peptide as a cellular response for recycling the damaged organelles, through molecular mediation associated with the change of mitochondrial membrane potential. The biological effects induced by NP-peptide reciprocally affect the distribution patterns and fates of nanoparticles in the cell metabolism by providing an alternative route of intracellular trafficking. The new understanding of the mutual activities between nanoparticles and cells will enrich our approaches in the development of nanobiotechnology and nano-medicine for disease treatments. PMID- 26142777 TI - Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice. AB - Subcutaneous liver tissue engineering is an attractive and minimally invasive approach used to curative treat hepatic failure and inherited liver diseases. However, graft failure occurs frequently due to insufficient infiltration of blood vessels (neoangiogenesis), while the maintenance of hepatocyte phenotype and function requires in vivo development of the complex cellular organization of the hepatic lobule. Here we describe a subcutaneous human liver construction allowing for rapidly vascularized grafts by transplanting engineered cellular sheets consisting of human primary hepatocytes adhered onto a fibroblast layer. The engineered hepatocyte/fibroblast sheets (EHFSs) showed superior expression levels of vascularization-associated growth factors (vascular endothelial growth factor, transforming growth factor beta 1, and hepatocyte growth factor) in vitro. EHFSs developed into vascularized subcutaneous human liver tissues contained glycogen stores, synthesized coagulation factor IX, and showed significantly higher synthesis rates of liver-specific proteins (albumin and alpha 1 anti-trypsin) in vivo than tissues from hepatocyte-only sheets. The present study describes a new approach for vascularized human liver organogenesis under mouse skin. This approach could prove valuable for establishing novel cell therapies for liver diseases. PMID- 26142778 TI - Remote modulation of neural activities via near-infrared triggered release of biomolecules. AB - The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of use will likely make our optically-controlled delivery technology a general and important tool in cell biology research. PMID- 26142779 TI - A biomimetic Schlemm's canal inner wall: A model to study outflow physiology, glaucoma pathology and high-throughput drug screening. AB - Glaucoma is a disease that damages the optic nerve, frequently leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, which is expected to affect 80 million people by 2020, causing bilateral blindness in over 10 million individuals. Because pathological changes to Schlemm's canal (SC) may account for significant resistance to outflow, there is considerable interest in characterizing and evaluating the Schlemm's canal as a target for glaucoma therapeutics. In conventional, two-dimensional culture, human Schlemm's canal (HSC) cells lose spatial, mechanical and biochemical cues, resulting in altered gene expression and cell signaling than observed in vivo, compromising the clinical relevance of data obtained from such systems. Here, we report, for the first time, that 3D culture of HSC cells on microfabricated scaffolds with defined physical and biochemical cues, rescued expression of key HSC markers, VE-cadherin and PECAM1, and mediated pore formation, crucial for the Schlemm's canal regulation of IOP. We demonstrated that following treatment with the glaucopathogenic agent, TGF-beta2, HSC cells undergo an endothelial mesenchymal transition, which together with the increase in extracellular matrix (ECM) proteins might account for the decrease in outflow facility observed in patients with high TGF-beta2 levels in their aqueous humor. We also demonstrated that unlike 2D cultures, 3D cultures of HSC cells are amenable to gene transfer. Thus, our data imply that 3D culture of HSC cells may be used as a platform to advance our understanding of HSC physiology and pathology and as a model for high throughput drug and gene screening. PMID- 26142781 TI - In silico attempt for adduct agent(s) against malaria: Combination of chloroquine with alkaloids of Adhatoda vasica. AB - With the aim of controlling drug resistant Plasmodium falciparum, a computational attempt of designing novel adduct antimalarial drugs through the molecular docking method of combining chloroquine with five alkaloids, individually is presented. These alkaloids were obtained from the medicinal plant, Adhatoda vasica. From the obtained individual docking values of important derivatives of quinine and chloroquine, as well as, individual alkaloids and adduct agents of chloroquine with Adhatoda alkaloids as ligands, it was discernible that the 'adduct agent-1 with chloroquine and adhatodine' combination had the minimum energy of interaction, as the docking score value of -11.144 kcal/mol against the target protein, triosephosphate isomerase (TIM), the key enzyme of glycolytic pathway. Drug resistance of P. falciparum is due to a mutation in the polypeptide of TIM. Moratorium of mutant TIM would disrupt the metabolism during the control of the drug resistant P. falciparum. This in silico work helped to locate the 'adduct agent-1 with chloroquine and adhatodine', which could be taken up by pharmacology for further development of this compound as a new drug against drug resistant Plasmodium. PMID- 26142782 TI - Spatial learning-related changes in metabolic brain activity contribute to the delimitation of the hippocampal pallium in goldfish. AB - Comparative neuroanatomical, developmental and functional evidence suggests that the lateral division of the area dorsalis telencephali (Dl) of the teleost fish is homologous to the hippocampus of tetrapods. Nonetheless, some important aspects of the organization of the hippocampal pallium of teleosts are still under discussion and conflicting hypotheses regarding the extension and demarcation of this region have been proposed. Thus, whereas some authors suggest that the entire Dl region, including its dorsal (Dld) and ventral (Dlv) subdivisions, is homologue to the mammalian hippocampus, others claim that only Dlv should be considered as such. To further elucidate this debate, we investigated the role of Dld and Dlv in one of the most unambiguous functions of the hippocampus, spatial learning. We trained goldfish in a spatial constancy task and mapped the activity of Dld, Dlv, and the medial division of the area dorsalis telencephali (Dm) by means of cytochrome oxidase (CO) histochemistry. The results revealed that training goldfish in the spatial constancy task significantly increased the metabolic activity in Dlv, but not in Dld or Dm, suggesting that only Dlv is critically involved in spatial learning and in this regard comparable to the hippocampus. These data provide additional functional support to the hypotheses that consider Dl as a heterogeneous pallial region and propose that Dlv, but not Dld, might be homologous to the hippocampus. PMID- 26142780 TI - Biodegradable nano-films for capture and non-invasive release of circulating tumor cells. AB - Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype change, therefore losing valuable information about the isolated cells. We present a biodegradable nano-film coating on the surface of a microfluidic chip, which can be used to effectively capture as well as non-invasively release cancer cell lines such as PC-3, LNCaP, DU 145, H1650 and H1975. We have applied layer-by layer (LbL) assembly to create a library of ultrathin coatings using a broad range of materials through complementary interactions. By developing an LbL nano film coating with an affinity-based cell-capture surface that is capable of selectively isolating cancer cells from whole blood, and that can be rapidly degraded on command, we are able to gently isolate cancer cells and recover them without compromising cell viability or proliferative potential. Our approach has the capability to overcome practical hurdles and provide viable cancer cells for downstream analyses, such as live cell imaging, single cell genomics, and in vitro cell culture of recovered cells. Furthermore, CTCs from cancer patients were also captured, identified, and successfully released using the LbL-modified microchips. PMID- 26142783 TI - Rats with differential self-grooming expression in the elevated plus-maze do not differ in anxiety-related behaviors. AB - Individual differences are important biological predictors for reactivity to stressful stimulation. The extent to which trait differences underlie animal's reactions to conditioned and unconditioned fear stimuli, for example, is still to be clarified. Although grooming behavior has been associated with some aspects of the obsessive-compulsive disorder in humans, its relation with other anxiety disorders is still unknown. Given that grooming behavior could be a component of the whole spectrum of these disorders, in the present study we allocated male Wistar rats in low, intermediate and high self-grooming groups according to the duration of such behavior in the elevated plus-maze (EPM). These groups were then evaluated in unconditioned fear tests, such as the EPM and the open-field, and in conditioned fear tests, such as fear-potentiated startle and fear extinction retention. Additionally, we studied the expression of unconditioned behaviors in marble burying test and the sensorimotor gate function with prepulse inhibition test. Neurochemicals and neuroendocrine parameters were also evaluated, with the quantification of basal corticosterone in the plasma, and dopamine, serotonin and their metabolites in brain structures involved with fear processing. In general, rats classified according to grooming expression showed similar performance in all behavioral tests. Accordingly, corticosterone and monoamine concentrations were similar among groups. Thus, despite grooming expression elicited by different approaches--especially pharmacological ones--has been related with some aspects of anxiety disorders, rats with different expression of spontaneous self grooming in the EPM do not differ in anxiety-like behaviors nor in neurochemical and neuroendocrine parameters generally associated with anxiety disorders. PMID- 26142784 TI - [Mechanical support to the lead extraction]. PMID- 26142785 TI - [Turkish Adult Risk Factor survey 2014: Overall mortality and coronary disease incidence in Turkey's geographic regions]. AB - OBJECTIVE: This study aimed to examine the overall and coronary mortality in the 2014 Turkish Adult Risk Factor Study survey, and the distribution of cumulative mortality and incident coronary heart disease (CHD) across 7 geographic regions. METHODS: Information on mode of death was appropriately obtained. Information collected from survivors was based on history, examination of the cardiovascular system and the Minnesota coding of electrocardiograms. Cox regression analyses were performed. RESULTS: Of the 1.323 participants to be surveyed, 87 were lost to follow-up, 753 examined, and 35 ascertained as deceased. In 448 subjects, verbal information alone was obtained regarding health status. Nineteen deaths were of coronary and cerebrovascular origin. Cumulative 24-year assessment of the entire cohort in the age bracket 45-74 years disclosed high coronary mortality, at 7.3 per 1000 person-years in men and 3.8 in women, and recorded a limited decline of 18% since the year 2000. Age-adjusted Cox regression analysis, comprising 614 deaths and 482 incident CHD over a follow-up of 9.6 years, revealed higher mortality rates in the Mediterranean region and in men in the Black Sea and Marmara regions. The age-adjusted CHD incidence was significantly higher in males of the Mediterranean and females of the Southeast regions. An estimated 400-420.000 incident CHD cases develop currently each year in Turkey. CONCLUSION: The generally high age-adjusted overall mortality in Turkey displays significant differences across geographic regions. Age-adjusted CHD incidence is not regressing sufficiently, and is especially high among men of the Mediterranean and women of the Southeast regions. PMID- 26142786 TI - Serum YKL-40/chitinase 3-like protein 1 level is an independent predictor of atherosclerosis development in patients with obstructive sleep apnea syndrome. AB - OBJECTIVE: The inflammatory process plays an important role in the development of cardiovascular complications in patients with obstructive sleep apnea syndrome (OSAS). YKL-40/chitinase 3-like protein 1 is a novel biomarker of systemic inflammation. This study aimed to investigate whether carotid intima-media thickness (CIMT), a useful marker for early atherosclerosis, is associated with serum YKL-40/chitinase 3-like protein 1 levels in patients with normotensive and nondiabetic OSAS. METHODS: The study included 40 OSAS patients and 40 age- sex- and body mass index-matched healthy controls. Serum YKL-40 levels were detected by enzyme-linked immunosorbent assay. CIMT was measured by B-mode ultrasound. RESULTS: The patients with OSAS had significantly increased CIMT and higher YKL 40 and high sensitivity C-reactive protein (hsCRP) levels than those of the controls. CIMT was strongly correlated with serum YKL-40 levels (r=0.694, p<0.001), hsCRP (r=0.622, p<0.001), age (r=0.525, p=0.001), and weakly correlated with apnea-hypopnea index (AHI) (r=0.365, p=0.021) and the percentage of recording time spent (PRTS) of oxygen saturation<90% (r=0.488, p=0.001). Moreover, it was detected that serum YKL-40 levels were strongly correlated with AHI (r=0.617, p<0.001), and weakly correlated with SaO2<90% of PRTS (r=0.394, p=0.012) and hsCRP (r=0.486, p=0.001). In multiple regression analyses, age and serum levels of YKL-40 and hsCRP were found to be independent predictors of CIMT. CONCLUSION: In patients with OSAS, CIMT was increased. This increase was associated with serum YKL-40 level. Increased serum level of YKL-40 may be an early predictor of atherosclerosis development in patients with OSAS. PMID- 26142787 TI - The relation between compliance to the Mediterranean diet and the extensiveness of coronary artery disease. AB - OBJECTIVE: There are various studies showing the cardiovascular benefits of the Mediterranean diet (MD), but, to the best of our knowledge, this is the first study which aimed to investigate the relation between adherence to the MD and severity of coronary artery disease (CAD). METHODS: The study was a single centre, cross-sectional prospective study which included 200 consecutive patients (131 men [65.5%] and 69 women [34.5%], mean age 57+/-9) who were diagnosed with CAD by coronary angiography between January 2012 and April 2013. A food frequency questionnaire was administered to the patients. Compliance to the MD was evaluated by the MD score (MDS), which collects prominent diet characteristics under 10 main titles. Each patient's angiographic data was examined by a cardiologist, and Gensini scores (GS) were then calculated to evaluate the extensiveness of coronary atherosclerosis. RESULTS: Forty-four percent of patients were in the third category of body mass index (BMI) (>=30 kg/m2) and 17.5% were in the first category (BMI<25 kg/m2). Education levels were markedly low, with 78% of the patients having fewer than six years in education. Most patients had low physical activity levels (55.5%). Frequency of metabolic syndrome was prominent (79%). The median (25-75 percentiles) of GS was found to be 21.25 (7-44.75) and the MD score was 4 (3-5). A negative correlation was found between compliance to the MD and GS (r=-0.380, p<0.001). CONCLUSION: This study found that in patients with CAD, compliance with the traditional MD is related to decreased severity of coronary atherosclerosis. PMID- 26142788 TI - [Evaluation of lead extraction procedures using the Evolution Mechanical Dilatator Sheath lead extraction system: A single centre experience]. AB - OBJECTIVE: In recent years, there has been an increase in clinical situations requiring extraction of leads of implanted cardiac devices. This study aimed to evaluate the Evolution Mechanical Dilator Sheath system, presently in use in our clinic for lead extraction procedures. METHODS: Lead extraction procedures carried out on 20 patients (14 men, 6 women; mean age 61+/-19; range 23 to 85 years) between 2008 and 2013 using the Evolution system were retrospectively evaluated. Procedural success, and major and minor complications were determined by previously published guidelines. RESULTS: Mean implantation duration of the leads was 97+/-65 months (8-204). Fifteen (75%) patients had undergone pacemaker implantation and 5 (25%) had been implanted with a defibrillator. A total of 35 leads were removed from the patients. Seventeen (49%) were ventricular and 12 (34%) were atrial. Five (14%) were defibrillator coils and 1 a coronary sinus lead. Indications for lead extraction were device infection in 18 (90%) patients and lead dysfunction in 2 (10%). Complete procedural success was 95%. Failure occurred in 1 patient. The major complication rate was 5% and minor complications were seen in 25% of patients. No case of mortality was present. CONCLUSION: In this single centre study, it was shown that extraction of pacemaker and defibrillator leads of longer implant duration may be successfully carried out using the Evolution system. However, due to potentially serious complications it is advised that extraction be done by an experienced operator in centres with cardiovascular surgery facilities. PMID- 26142789 TI - [Evaluation of quality of life using the Umea 22 questionnaire among patients with atrioventricular nodal tachycardia undergoing successful radiofrequency ablation treatment]. AB - OBJECTIVE: Atrioventricular nodal reentrant tachycardia (AVNRT) attacks is one of the common arrhythmias adversely affecting quality of life. The Umea 22 (U22) is a questionnaire developed for the assessment of symptoms associated with supraventricular tachycardia (SVT), and it is found to be effective in evaluation of quality of life after radiofrequency ablation. Using this questionnaire, the study aimed to assess quality of life among Turkish patients with ANRT before and after the successful RFA. METHODS: The study was conducted between January 2011 and September 2013, and included 57 patients who had undergone RFA due to AVNRT. The U22 questionnaire was administered pre-procedure and at 6 months post procedure. The participants were asked to report on their general well-being, arrhythmia effects on their wellbeing, and intensity of discomfort associated with episodes. They were asked to provide a score from 1 to 10 in order to determine to severity of discomfort, and the quantity of symptoms was then assessed according to the visual analogue scale (VAS). RESULTS: Patients' general wellbeing (7.5+/-2.3 vs. 8.7+/-1.8, p<0.001), the effects of arrhythmia episodes on general well-being (8.1+/-1.7 vs. 1.0+/-2.1, p<0.001), frequency of symptoms (2.8+/-0.8 vs. 0.4+/-0.9, p<0.001) and duration of symptoms were reduced significantly after RFA. The rate of drug use among patients also decreased after RFA (70% vs. 23%, p=0.017). CONCLUSION: Treatment success was high in patients undergoing RFA due to AVNRT according to the U22 quality of life questionnaire. General and arrhythmia-associated quality of life had improved significantly by the 6th month post-procedure. PMID- 26142790 TI - [Levels of awareness of occupational and general cardiovascular risk factors among metal industry employees]. AB - OBJECTIVE: Long-term exposure to physical, chemical, ergonomic and psychosocial environmental factors may lead to occupational cardiovascular disease in metal industry employees. This study aimed to determine levels of knowledge levels regarding occupational and cardiovascular risk factors among metal industry employees. METHODS: The study was conducted between 2nd and 6th June 2014 with the participation of 82 employees. All were working in a medium-sized workplace in the metal industry. Data were collected by means of a questionnaire, which included socio-demographic characteristics and occupational cardiovascular risk factors, and a scale developed by Arikan et al. to measure awareness levels of risk factors for cardiovascular diseases (CARRF-KL). RESULTS: The mean age of employees was 39.97+/-8.44. Of the participants, 58.5% stated that they had knowledge on cardiac disease risk factors. The mean CARRF-KL score was found to be 18.65+/-4.04. The percentage of employees stating that they had no knowledge on the occupational risks for such diseases was 79.3%, while 19.5% stated that job stress caused cardiac diseases. One individual (1.2%) stated that one of the chemical solvents used in the working environment was a risk factor. CONCLUSION: Although awareness among metal industry employees of cardiovascular risk factors was above average, it was determined that they do not have adequate information on occupational risk factors. Prolonged and unprotected levels exposure to environmental factors constitute a risk for cardiovascular disease. This information is important for the development of preventive cardiology. PMID- 26142791 TI - Implantation of a cardiac resynchronization therapy-defibrillator device in a patient with persistent left superior vena cava. AB - Presence of a persistent left superior vena cava (PLSVC) is generally clinically asymptomatic and discovered incidentally during central venous catheterization. However, PLSVC may cause technical difficulties during cardiac device implantation. An 82-year-old man with heart failure symptoms and an ejection fraction (EF) of 20% was scheduled for resynchronization therapy-defibrillator device (CRT-D) implantation. A PLSVC draining via a dilated coronary sinus into an enlarged right atrium was diagnosed. First, an active-fixation right ventricular lead was inserted into the right atrium through the PLSVC. The stylet was preshaped to facilitate its passage to the right ventricular apex. An atrial lead was positioned on the right atrium free wall, and an over-the-wire coronary sinus lead deployed to a stable position. CRT-D implantation procedure was successfully completed. PMID- 26142792 TI - Multimodality imaging of a recurrent case of right-sided cardiac leiomyosarcoma with an unusual clinical course. AB - Primary cardiac sarcoma is an uncommon entity and is related with poor long-term survival. Presented here is an unusual case of right atrial leiomyosarcoma which almost completely occluded both the right atrium and ventricle and destroyed the tricuspid valve. Multimodality imaging was used to characterize the mass and guide surgical management. A combination of two radical surgical excisions and both radiation and chemotherapy resulted in a better long-term outcome. The patient was one of the longest survivors. PMID- 26142793 TI - Optimal treatment of unligated side branch of internal mammary artery: Coil, amplatzer vascular plug or graft stent? A case report and literature review. AB - Coronary artery steal syndromes may occur following coronary artery bypass grafting as a result of the presence of large side-branches arising from the internal mammary artery (IMA). Coil embolization, Amplatzer Vascular Plug and graft stents are all used for the treatment of such syndromes. The literature contains limited data on the long-term success of these treatment methods. There is no large series regarding occluded IMA side branches causing coronary steal phenomena, and data on long-term follow-up of this treatment method is also very limited. This report presented two cases and their treatment, and reviewed the advantages and disadvantages of treatment methods and the factors that affect successful treatment. PMID- 26142794 TI - Peripheral self-expandable stent catheter fracture: Retrieval of two different components with two different modalities. AB - A 58-year-old man whose right superficial femoral artery had been stented 2 weeks previously presented at the emergency service complaining of right leg pain of 2 days' duration. Angiography revealed a radiopaque foreign body distal to the stent. It was removed with a snare. Due to sudden disappearance of the popliteal artery pulse seventy-two hours after the procedure, an urgent control angiogram was performed, which showed a large thrombus occluding the superficial femoral artery. Surgery revealed a second larger radiolucent foreign body causing the thrombus. This was recognized as the distal tip and shaft of the peripheral self expandable stent catheter used in the initial procedure. This report discusses preventive measures to be taken against this complication. PMID- 26142795 TI - Successful percutaneous coronary intervention for acute coronary syndrome in a patient with haemophilia B. AB - Haemophilia is a congenital coagulation defect brought about by the deficiency or lack of coagulation factor IX. The prevalence of coronary artery disease and acute coronary syndrome (ACS) is lower among haemophiliacs than in the normal population. However, with the administration of factor concentrate, average life expectancy can now extend to as long as 70 years in patients with haemophilia, and this in turn is leading to an increase in the prevalence of cardiac diseases among this population. Data regarding a treatment protocol for ACS and percutaneous coronary intervention (PCI) in patients with congenital coagulation defects is limited. We report a 41-year-old male patient with haemophilia B who presented with a non-ST elevation myocardial infarction, and on whom PCI was performed following monitoring of factor IX levels. The patient had no cardiovascular risk factor except smoking. PMID- 26142796 TI - [A rare complication of cardiac radiofrequency catheter ablation: Esophageal irritation]. AB - The complication rate of radiofrequency catheter ablation varies depending on patient characteristics and treatment, and has been reported to be approximately 3%. Esophageal irritation is one significant complication of catheter ablation, and its most common result is atrio-esophageal fistulae. However, rarely, unexpected complications and clinical variants occur due to irritation of the vagal nerve or peri-esophageal tissue without fistula formation. In this case report, attention is drawn to this rare complication in two cases, one of which occurred after paraseptal-epicardial accessory pathway ablation, and the other after atrial fibrillation ablation. Both were symptomatic with severe gag reflex. PMID- 26142797 TI - Electrophysiological correlates of cardiac sarcoidosis: an appraisal of current evidence. AB - Cardiac sarcoidosis is an underdiagnosed condition that may be present in as many as 25% of patients with systemic sarcoidosis. It is associated with significant morbidity and mortality in affected individuals. The presentation of cardiac involvement in sarcoidosis includes sudden death in the absence of preceding symptoms, conduction disturbances, ventricular arrhythmias, and heart failure. A scarcity of randomized data and a lack of prospective trials underlies the contention between experts on the most appropriate strategies for diagnosis and therapy. This review focuses on the electrophysiological sequelae of the disease, with an emphasis on current diagnostic guidelines, multimodality imaging for early detection, and the role of various therapeutic interventions. Multicentre collaboration is necessary to address the numerous unanswered questions pertaining to management of this disease. PMID- 26142798 TI - [Turkish Hypertension Consensus Report]. AB - Hypertension is a common and important public health problem in Turkey and worldwide. Recommendations on the diagnosis and treatment of hypertension have been presented in many nationally and internationally agreed European and American guidelines. However, there are differences among these guidelines, and some of the recommendations are not consistent with clinical practice in our country. Consensus report preparation, with the participation of relevant associations, was considered necessary to merge recommendations by evaluating hypertension guidelines from the perspective of Turkey and to create a joint approach in the diagnosis and treatment of hypertension in adults. For this purpose, it was aimed to prepare a practical text in Turkey in which all physicians dealing with hypertensive patients, from family practitioners in primary care to specialists in tertiary care, could come to agreement on common concepts, and which would be used as a basic reference guideline. Considering health care practices and sociocultural structure in Turkey, this report aimed to enhance awareness on hypertension, provide a common basis for different definitions and values as well as therapeutic options in various guidelines, and establish a practical reference guide to improve clinical practices in Turkey. This report is not a document describing hypertension in every aspect, but a reference, including basic recommendations with outlines. Care was taken to ensure that recommendations were evidence-based and valid for a majority of patients in clinical practice. However, it should be kept in mind that an approach assessment should be made on an individual basis for each patient. PMID- 26142799 TI - [Case images: A rare complication of left ventriculography: Intramyocardial injection]. PMID- 26142800 TI - Case images: D-transposition of the great arteries with bilateral peripheral pulmonary artery stenosis and arcus hypoplasia: A rare association. PMID- 26142801 TI - Case images: A totally extruded pacemaker. PMID- 26142802 TI - [Case images: Superior vena cava rupture during an ICD implantation and its management]. PMID- 26142803 TI - Case images: A giant left main coronary artery aneurysm. PMID- 26142804 TI - Letter to the Editor: Another therapeutic target for atherosclerosis. PMID- 26142805 TI - A comparative study of the neutron flux spectra in the MNSR irradiation sites for the HEU and LEU cores using the MCNP4C code. AB - A comparative study for fuel conversion from the HEU to LEU in the Miniature Neutron Source Reactor (MNSR) has been performed in this paper using the MCNP4C code. The neutron energy and lethargy flux spectra in the first inner and outer irradiation sites of the MNSR reactor for the existing HEU fuel (UAl4-Al, 90% enriched) and the potential LEU fuels (U3Si2-Al, U3Si-Al, U9Mo-Al, 19.75% enriched and UO2, 12.6% enriched) were investigated using the MCNP4C code. The neutron energy flux spectra for each group was calculated by dividing the neutron flux by the width of each energy group. The neutron flux spectra per unit lethargy was calculated by multiplying the neutron energy flux spectra for each energy group by the average energy of each group. The thermal neutron flux was calculated by summing the neutron fluxes from 0.0 to 0.625 eV, the fast neutron flux was calculated by summing the neutron fluxes from 0.5 MeV to 10 MeV for the existing HEU and potential LEU fuels. Good agreements have been noticed between the flux spectra for the potential LEU fuels and the existing HEU fuels with maximum relative differences less than 10% and 8% in the inner and outer irradiation sites. PMID- 26142806 TI - Application of spectral decomposition of 222Rn activity concentration signal series measured in Niedzwiedzia Cave to identification of mechanisms responsible for different time-period variations. AB - The authors present an application of spectral decomposition of (222)Rn activity concentration signal series as a mathematical tool used for distinguishing processes determining temporal changes of radon concentration in cave air. The authors demonstrate that decomposition of monitored signal such as (222)Rn activity concentration in cave air facilitates characterizing the processes affecting changes in the measured concentration of this gas. Thanks to this, one can better correlate and characterize the influence of various processes on radon behaviour in cave air. Distinguishing and characterising these processes enables the understanding of radon behaviour in cave environment and it may also enable and facilitate using radon as a precursor of geodynamic phenomena in the lithosphere. Thanks to the conducted analyses, the authors confirmed the unquestionable influence of convective air exchange between the cave and the atmosphere on seasonal and short-term (diurnal) changes in (222)Rn activity concentration in cave air. Thanks to the applied methodology of signal analysis and decomposition, the authors also identified a third process affecting (222)Rn activity concentration changes in cave air. This is a deterministic process causing changes in radon concentration, with a distribution different from the Gaussian one. The authors consider these changes to be the effect of turbulent air movements caused by the movement of visitors in caves. This movement is heterogeneous in terms of the number of visitors per group and the number of groups visiting a cave per day and per year. Such a process perfectly elucidates the observed character of the registered changes in (222)Rn activity concentration in one of the decomposed components of the analysed signal. The obtained results encourage further research into precise relationships between the registered (222)Rn activity concentration changes and factors causing them, as well as into using radon as a precursor of geodynamic phenomena in the lithosphere. PMID- 26142807 TI - An affordable optically stimulated luminescent dosimeter reader utilizing multiple excitation wavelengths. AB - A lower-cost optically stimulated luminescence (OSL) reader with increased flexibility for pursuing laboratory research into OSL theory and application was designed and constructed. This was achieved by using off-the-shelf optical components and higher-power light emitting diodes. The resulting reader includes more wavelengths of excitation light than current commercial readers, as well as the ability to swap out filters and other components during an experiment. PMID- 26142808 TI - Dose response, radiation sensitivity and signal fading of p-channel MOSFETs (RADFETs) irradiated up to 50 Gy with 60Co. AB - This paper reports response of p-channel MOSFETs (RADFETs) to (60)Co gamma radiation in the 10-50 Gy dose range and signal fading (room temperature annealing) for 100 days after irradiation. RADFETs with three different thicknesses of the gate oxide layer were used. Irradiations were performed at gate biases ranging from 0 to 5 V. Threshold voltage shift was monitored during the irradiations and the subsequent fading. The dependence of the threshold voltage shift on the radiation dose is linear for the RADFETs with 100 nm- and 400 nm-thick gate oxide layers irradiated under the gate biases ranging from 1.25 to 5 V. Also, an exponential dependence of the radiation sensitivity on the gate bias during irradiation was found. The signal fades at room temperature without a gate bias. The results demonstrate that these RADFETs are suitable as sensors of gamma radiation. The threshold voltage shift of the RADFETs with 400 nm- and 1 MUm-thick gate oxide layers decreases significantly during the first day after irradiation, which, unfortunately, makes these devices incapable of holding dosimetric information for long periods of time. PMID- 26142809 TI - Target development for diversified irradiations at a medical cyclotron. AB - The irradiation facility at an old medical cyclotron (Ep=17 MeV; Ed=10 MeV) was upgraded by extending the beam line and incorporation of solid state targetry. Tests performed to check the quality of the available beam are outlined. Results on nuclear data measurements and improvement of radiochemical separations are described. Using solid targets, with the proton beam falling at a slanting angle of 20 degrees , a few radionuclides, e.g. (75)Se, (120)I, (124)I, etc. were produced with medium currents (up to 20 uA) in no-carrier-added form in quantities sufficient for local use. The extended irradiation facility has considerably enhanced the utility of the medical cyclotron. PMID- 26142810 TI - Cell Therapy: Engineering and Manufacture of Pluripotent Cells. PMID- 26142811 TI - Awake Craniotomy in Arteriovenous Malformation Surgery: The Usefulness of Cortical and Subcortical Mapping of Language Function in Selected Patients. AB - OBJECTIVE: Awake craniotomy for removal of intra-axial lesions is a well established procedure. Few studies, however, have investigated the usefulness of this approach for resection of arteriovenous malformations adjacent to eloquent language areas. We demonstrate our experience by using cortical stimulation mapping and report for the first time on the usefulness of subcortical stimulation with interrogation of language function during resection of arteriovenous malformations (AVMs) located near language zones. METHODS: Patients undergoing awake craniotomy for AVMs located in language zones and at least 5 mm away from the closest functional magnetic resonance imaging activation were analyzed. During surgery, cortical bipolar stimulation at 50 Hz, with an intensity of 2 mA, increased to a maximum of 10 mA was performed in the region around the AVM before claiming it negative for language function. In positive language site, the area was restimulated 3 times to confirm the functional deficit. The AVM resection was started based on cortical mapping findings. Further subcortical stimulation performed in concert with speech interrogation by the neuropsychologist continued at key points throughout the resection as feasible. The usefulness of cortical and subcortical stimulation in addition to patient outcomes was analyzed. RESULTS: Between March 2009 and September 2014, 42 brain AVM resections were performed. Four patients with left-sided language zone AVMs underwent awake craniotomy. The AVM locations were fronto-opercular in 2 patients and posterior temporal in 2. The AVM Spetzler-Martin grades were II (2 patients) and III (2 patients). In 1 patient, complete speech arrest was noticed during mapping of the peri-malformation zone, which was not breached during resection. In a second patient who initially demonstrated negative cortical mapping, a speech deficit was noticed during resection and subcortical stimulation. This guided the approach to protect and avoid the sensitive zone. This patient experienced mild postoperative expressive dysphasia that improved to normal within 6 weeks. Complete resection was achieved in all 4 patients. There were no other complications and no permanent neurological morbidity, resulting in good outcome in all 4 patients. CONCLUSIONS: Language mapping, both cortical and subcortical during AVM resection, may be valuable in a very select group of AVMs in language zones. Defining safe margins and feedback to the surgeon may provide the highest chances of a surgical cure while minimizing the risk of incurring a language deficit. PMID- 26142812 TI - The Preinterventional Psychiatric History as a Major Predictor for a Reduced Quality of Life After Treatment of Unruptured Intracranial Aneurysms. AB - BACKGROUND: A significantly increased rate of positive preinterventional psychiatric histories in the unruptured aneurysm collective was demonstrated previously. The current study was designed to analyze the influence of the preinterventional psychiatric status on the outcome after treatment of unruptured intracranial aneurysms. METHODS: Patients treated due to meningioma World Health Organization degrees I and unruptured intracranial aneurysms in 2 German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm, and neurologic deficits among others. The preinterventional psychiatric histories and the rates of postinterventional headaches, sleeping disorders, symptoms of chronic fatigue syndrome, and quality of life (QOL) were determined by questionnaires that were mailed to the patients in a printed version. RESULTS: A total of 58 M patients and 45 iA patients who met the inclusion criteria returned the questionnaires; 10 M (17.2%) and 17 iA patients (37.8%) had a positive psychiatric history. The overall Incidental aneurysm collective demonstrated significantly lower overall QOL scores (P = 0.003) and significant greater rates of chronic fatigue syndrome (P = 0.009) compared with the M collective. After we excluded all patients with positive pre-interventional psychiatric histories, those differences were no longer reproducible. Subjectively, the patients did not realize any significant changes in their QOL after successful aneurysm treatment. CONCLUSIONS: The results of the current study demonstrate the importance of taking the preinterventional psychiatric history into considerations when evaluating the outcome after unruptured aneurysm treatment. The unfavorable outcome of the aneurysm group seems to be caused by factors that are not related the aneurysm diagnosis or treatment itself. PMID- 26142813 TI - Primary Central Nervous System Natural Killer Cell Lymphoma in a Chinese Woman with Atypical (11)C-Choline Positron Emission Tomography and Magnetic Resonance Spectrometry Findings. AB - BACKGROUND: Primary central nervous system (CNS) natural killer (NK)-cell lymphoma is rare with only 7 cases reported previously. Magnetic resonance spectroscopy (MRS) and [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) are frequently used for disease diagnosis and monitoring. Choline (CHO) PET is gaining popularity for identifying CNS lesions because of its high disease to background radioactivity ratio compared with FDG. Normally, CNS lymphoma shows high choline uptake on CHO-PET and a high choline peak on MRS. We present an unusual case of primary CNS NK-cell lymphoma with high choline uptake but absence of a high choline peak on MRS. CASE DESCRIPTION: A 39-year-old woman presented with subacute onset of cognitive deterioration. Magnetic resonance imaging of the brain showed a gadolinium-enhancing lesion in the left temporal lobe. MRS showed suppressed N-acetyl-aspartate and the absence of a high choline peak. CHO-PET confirmed that it was the only hypermetabolic lesion in the body with moderate uptake of choline. The differential diagnoses included encephalitis and neoplasm. She was initially treated for the former but did not respond to steroids, intravenous immunoglobulin, and plasmapheresis. A surgical biopsy later confirmed NK-cell lymphoma. She was then treated as primary CNS NK cell lymphoma with intravenous and intrathecal chemotherapy. CONCLUSIONS: We presented a unique case of primary CNS NK-cell lymphoma with atypical imaging findings characterized by moderately increased uptake of choline without a corresponding high choline peak on MRS. Although CHO-PET was suggestive of malignancy, surgical biopsy was required to confirm the diagnosis. PMID- 26142814 TI - Synchronous Subarachnoid Aneurysmal Hemorrhage and Medulloblastoma in a 6-Year Old Girl. AB - BACKGROUND: Hemorrhage in medulloblastoma (MB) is a rare clinical entity with the undeniable potential for catastrophic repercussions. This case report highlights the first incidence of intraoperative subarachnoid hemorrhage (SAH) in a patient with MB secondary to an intracranial aneurysm. CASE DESCRIPTION: A 6-year-old girl with a left cerebellar mass, fourth ventricle effacement, and triventriculomegally had an external ventricular drain inserted, at which time blood stained cerebral spinal fluid was drained. After insertion of an external ventricular drain, imaging showed diffuse SAH. Post tumor resection scans showed a small residuum of tumor. At repeat tumor resection after chemoradiotherapy, a 2 mm internal carotid aneurysm was noted. CONCLUSIONS: Intraoperative hemorrhage in MB is a very rare occurrence. We describe the first case of hemorrhage in MB secondary to an intracranial aneurysm. MB has a predisposition to bleed spontaneously that can have catastrophic repercussions. Sudden clinical deterioration after insertion of external ventricular drainage should be susceptive of intracerebral hemorrhage. In cases of uncertain etiology, investigation of SAH with cerebral angiography is recommended. PMID- 26142815 TI - Outcomes Research in Neurosurgery: Do Administrative Databases Hold the Answers? PMID- 26142816 TI - Dural Tail Sign in the Resection of Ventral Foramen Magnum Meningiomas via a Far Lateral Approach: Surgical Implications. AB - OBJECTIVE: To investigate the implications of dural tail sign (DTS) in the tailored far lateral approach for resection of ventral foramen magnum meningiomas (FMMs). METHODS: Clinical data for 16 patients treated surgically for ventral FMMs over 5 years were reviewed retrospectively. RESULTS: The DTS was positive in 11 cases (68.8%) and negative in 5 cases (31.2%). The most frequent form was a single cranial tail (7 of 11), followed by multiple tails consisting of a cranial tail and a caudal tail (3 of 11), and multiple tails composed of a cranial tail and a contralateral tail (1 of 11). The retrocondylar approach was carried out in 5 cases without DTS characterized by a narrow dural attachment and a partial transcondylar approach in 11 cases with DTS featuring a broad and hypervascular dural attachment. Drilling ranged from approximately one fifth to one third of the condyle with reference to the DTS form and tumor size. Total tumor removal was achieved in 16 patients. Postoperative complications were encountered in 25% of patients, predominantly associated with cranial nerve impairment. Follow-up ranging from 8 to 56 months (mean 24.4 months) showed no tumor recurrence. CONCLUSIONS: In addition to tumor dural attachment and tumor size, we propose that DTS should be considered as another factor in planning the surgical approach for ventral FMMs. Differentiation between a positive and negative DTS plays a role in the neurosurgical planning of ventral FMMs. Bone removal is warranted in tumors with DTS, particularly the multiple form with contralateral tails, to facilitate the surgical procedure and achieve a more radical resection. PMID- 26142817 TI - Radiocesium transfer from hillslopes to the Pacific Ocean after the Fukushima Nuclear Power Plant accident: A review. AB - The devastating tsunami triggered by the Great East Japan Earthquake on March 11, 2011 inundated the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) resulting in a loss of cooling and a series of explosions releasing the largest quantity of radioactive material into the atmosphere since the Chernobyl nuclear accident. Although 80% of the radionuclides from this accidental release were transported over the Pacific Ocean, 20% were deposited over Japanese coastal catchments that are subject to frequent typhoons. Among the radioisotopes released during the FDNPP accident, radiocesium ((134)Cs and (137)Cs) is considered the most serious current and future health risk for the local population. The goal of this review is to synthesize research relevant to the transfer of FDNPP derived radiocesium from hillslopes to the Pacific Ocean. After radiocesium fallout deposition on vegetation and soils, the contamination may remain stored in forest canopies, in vegetative litter on the ground, or in the soil. Once radiocesium contacts soil, it is quickly and almost irreversibly bound to fine soil particles. The kinetic energy of raindrops instigates the displacement of soil particles, and their bound radiocesium, which may be mobilized and transported with overland flow. Soil erosion is one of the main processes transferring particle-bound radiocesium from hillslopes through rivers and streams, and ultimately to the Pacific Ocean. Accordingly this review will summarize results regarding the fundamental processes and dynamics that govern radiocesium transfer from hillslopes to the Pacific Ocean published in the literature within the first four years after the FDNPP accident. The majority of radiocesium is reported to be transported in the particulate fraction, attached to fine particles. The contribution of the dissolved fraction to radiocesium migration is only relevant in base flows and is hypothesized to decline over time. Owing to the hydro-meteorological context of the Fukushima region, the most significant transfer of particulate-bound radiocesium occurs during major rainfall and runoff events (e.g. typhoons and spring snowmelt). There may be radiocesium storage within catchments in forests, floodplains and even within hillslopes that may be remobilized and contaminate downstream areas, even areas that did not receive fallout or may have been decontaminated. Overall this review demonstrates that characterizing the different mechanisms and factors driving radiocesium transfer is important. In particular, the review determined that quantifying the remaining catchment radiocesium inventory allows for a relative comparison of radiocesium transfer research from hillslope to catchment scales. Further, owing to the variety of mechanisms and factors, a transdisciplinary approach is required involving geomorphologists, hydrologists, soil and forestry scientists, and mathematical modellers to comprehensively quantify radiocesium transfers and dynamics. Characterizing radiocesium transfers from hillslopes to the Pacific Ocean is necessary for ongoing decontamination and management interventions with the objective of reducing the gamma radiation exposure to the local population. PMID- 26142818 TI - Prediction of terrestrial gamma dose rate based on geological formations and soil types in the Johor State, Malaysia. AB - This study aims to predict and estimate unmeasured terrestrial gamma dose rate (TGDR) using statistical analysis methods to derive a model from the actual measurement based on geological formation and soil type. The measurements of TGDR were conducted in the state of Johor with a total of 3873 measured points which covered all geological formations, soil types and districts. The measurements were taken 1 m above the soil surface using NaI [Ti] detector. The measured gamma dose rates ranged from 9 nGy h(-1) to 1237 nGy h(-1) with a mean value of 151 nGy h(-1). The data have been normalized to fit a normal distribution. Tests of significance were conducted among all geological formations and soil types, using the unbalanced one way ANOVA. The results indicated strong significant differences due to the different geological formations and soil types present in Johor State. Pearson Correlation was used to measure the relations between gamma dose rate based on geological formation and soil type (D(G,S)) with the gamma dose rate based on geological formation (D(G)) or soil type (D(s)). A very good correlation was found between D(G,S) and D(G) or D(G,S) and D(s). A total of 118 pairs of geological formations and soil types were used to derive the statistical contribution of geological formations and soil types to gamma dose rates. The contribution of the gamma dose rate from geological formation and soil type were found to be 0.594 and 0.399, respectively. The null hypotheses were accepted for 83% of examined data, therefore, the model could be used to predict gamma dose rates based on geological formation and soil type information. PMID- 26142819 TI - Coupling of anaerobic digester and microbial fuel cell for COD removal and ammonia recovery. AB - Microbial fuel cells (MFCs) were investigated for use in removing total ammonia nitrogen (TAN) and residual COD from effluent digested in an anaerobic digester (AD) fed with actual swine wastewater for 32 days in batch mode. Cumulative COD removal in the AD was as high as 59,647+/-2096 mg/L (80.5% removed), whereas TAN removal in the AD was negligible at 296+/-116 mg-N/L (5.8% removed), causing a decrease in the COD/TAN ratio from 14.5 to 3.0. In a subsequent MFC system, 77.5% of TAN was removed at 36 days, leading to an increase in COD/TAN ratio from 4.6 to 8.1. As a result, the COD in the anode was further reduced from 19,319+/-417 mg/L to 7519+/-554 mg/L (61.1% removed). From these results, removing the TAN in MFCs was found to increase the COD/TAN ratio, with the COD being further degraded. PMID- 26142820 TI - Pyrolyzed binuclear-cobalt-phthalocyanine as electrocatalyst for oxygen reduction reaction in microbial fuel cells. AB - A novel platinum (Pt)-free cathodic materials binuclear-cobalt-phthalocyanine (Bi CoPc) pyrolyzed at different temperatures (300-1000 degrees C) were examined as the oxygen reduction reaction (ORR) catalysts, and compared with unpyrolyzed Bi CoPc/C and Pt cathode in single chamber microbial fuel cells (SCMFCs). The results showed that the pyrolysis process increased the nitrogen abundance on Bi CoPc and changed the nitrogen types. The Bi-CoPc pyrolyzed at 800 degrees C contained a significant amount of pyrrolic-N, and exhibited a high electrochemical catalytic activity. The power density and current density increased with temperature: Bi-CoPc/C-800 > Bi-CoPc/C-1000 > Bi-CoPc/C-600 > Bi CoPc/C-300 > Bi-CoPc/C. The SCMFC with Bi-CoPc/C-800 cathode had a maximum power density of 604 mW m(-2). The low cost Bi-CoPc compounds developed in this study showed a potential in air-breathing MFC systems, with the proper pyrolysis temperature being chosen. PMID- 26142821 TI - A horizontal plug-flow baffled bioelectrocatalyzed reactor for the reductive decolorization of Alizarin Yellow R. AB - An application-oriented membrane-free, continuous plug-flow baffled bioelectrocatalyzed reactor (PFB-BER), was designed and testified for the decolorization of Alizarin Yellow R. Decolorization efficiency (DE) with an external power source of 0.5 V was higher than without electrolysis, i.e. 93.4% versus 73.6% (HRT of 24 h). Product formation efficiencies of p-phenylenediamine and 5-aminosalicylic acid were above 95% and 50%, respectively. When HRT decreased to 8 h and 4 h, DE reduced to 69.9% and 44.9%, respectively. An additional electrode assembly improved DE to 96.4% (HRT of 8 h) and 80% (HRT of 4 h), while energy consumption (HRT of 4 h) was lower than that of HRT of 12 h with single electrode assembly under comparable DE. The PFB-BER with higher removal capacity, lower internal resistance and energy consumption provides a new solution to treat the high loading azo dye-containing wastewaters. PMID- 26142822 TI - Catalytic Role of the Substrate Defines Specificity of Therapeutic l Asparaginase. AB - Type II bacterial L-asparaginases (L-ASP) have played an important therapeutic role in cancer treatment for over four decades, yet their exact reaction mechanism remains elusive. L-ASP from Escherichia coli deamidates asparagine (Asn) and glutamine, with an ~10(4) higher specificity (kcat/Km) for asparagine despite only one methylene difference in length. Through a sensitive kinetic approach, we quantify competition among the substrates and interpret its clinical role. To understand specificity, we use molecular simulations to characterize enzyme interactions with substrates and a product (aspartate). We present evidence that the aspartate product in the crystal structure of L-ASP exists in an unusual alpha-COOH protonation state. Consequently, the set of enzyme-product interactions found in the crystal structure, which guided prior mechanistic interpretations, differs from those observed in dynamic simulations of the enzyme with the substrates. Finally, we probe the initial nucleophilic attack with ab initio simulations. The unusual protonation state reappears, suggesting that crystal structures (wild type and a T89V mutant) represent intermediate steps rather than initial binding. Also, a proton transfers spontaneously to Asn, advancing a new hypothesis that the substrate's alpha-carboxyl serves as a proton acceptor and activates one of the catalytic threonines during L-ASP's nucleophilic attack on the amide carbon. That hypothesis explains for the first time why proximity of the substrate alpha-COO(-) group to the carboxamide is absolutely required for catalysis. The substrate's catalytic role is likely the determining factor in enzyme specificity as it constrains the allowed distance between the backbone carboxyl and the amide carbon of any L-ASP substrate. PMID- 26142823 TI - Interleukin-27 induces the endothelial differentiation in Sca-1+ cardiac resident stem cells. AB - Cytokines play important roles in cardiac repair and regeneration. Recently, we demonstrated that interleukin (IL)-6 family cytokines induce the endothelial differentiation of Sca-1+ cardiac resident stem cells through STAT3/Pim-1 signaling pathway. In contrast, the biological functions of IL-12 family cytokines in heart remain to be elucidated, though they show structural homology with IL-6. In the present study, we examined the effects of IL-12 family cytokines on the transdifferentiation of cardiac Sca-1+ cells into cardiac cells. RT-PCR analyses revealed that IL-27 receptor alpha (IL-27Ralpha), but not IL-12R or IL-23R, was expressed in cardiac Sca-1+ cells. The transcript expression of IL 27 was elevated in murine hearts in cardiac injury models. Intriguingly, IL-27 stimulation for 14 days induced the endothelial cell (EC) marker genes, such as CD-31 and VE-cadherin. Immunoblot analyses clarified that IL-27 treatment rapidly phosphorylated STAT3. IL-27 upregulated the expression of Pim-1, but the overexpression of dominant negative STAT3 abrogated the induction of Pim-1 by IL 27. Finally, adenoviral transfection of dominant negative Pim-1 inhibited IL-27 induced EC differentiation of cardiac Sca-1+ cells. These findings demonstrated that IL-27 promoted the commitment of cardiac stem cells into the EC lineage, possibly leading to neovascularization as a novel biological function. IL-27 could not only regulate the inflammation but also contribute to the maintenance of the tissue homeostasis through stem cell differentiation at inflammatory sites. PMID- 26142824 TI - Endothelial monocyte activating polypeptide II in children and adolescents with type 1 diabetes mellitus: Relation to micro-vascular complications. AB - OBJECTIVES: Endothelial monocyte-activating polypeptide II (EMAP II) is a multifunctional polypeptide with proinflammatory and antiangiogenic activity. Hyperglycemia and dyslipidemia appears to be significant factors contributing to increased EMAP-II levels. We determined serum EMAP II in children and adolescents with type 1 diabetes as a potential marker for micro-vascular complications and assessed its relation to inflammation and glycemic control. METHODS: Eighty children and adolescents with type 1 diabetes were divided into 2 groups according to the presence of micro-vascular complications and compared with 40 healthy controls. High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c) and EMAP II levels were assessed. RESULTS: Serum EMAP II levels were significantly increased in patients with micro-vascular complications (1539 +/- 321.5 pg/mL) and those without complications (843.6 +/- 212.6 pg/mL) compared with healthy controls (153.3 +/- 28.3 pg/mL; p<0.001). EMAP II was increased in patients with microalbuminuria than normoalbuminuric group (p<0.001). Significant positive correlations were found between EMAP II levels and body mass index, fasting blood glucose, HbA1c, serum creatinine, triglycerides, total cholesterol, urinary albumin creatinine ratio (UACR) and hs-CRP (p<0.05). A cutoff value of EMAP II at 1075 pg/mL could differentiate diabetic patients with and without micro-vascular complications with a sensitivity of 93% and specificity of 82%. CONCLUSIONS: We suggest that EMAP II is elevated in type 1 diabetic patients, particularly those with micro-vascular complications. EMAP II levels are related to inflammation, glycemic control, albuminuria level of patients and the risk of micro-vascular complications. PMID- 26142825 TI - The processing of polar quantifiers, and numerosity perception. AB - We investigated the course of language processing in the context of a verification task that required numerical estimation and comparison. Participants listened to sentences with complex quantifiers that contrasted in Polarity, a logical property (e.g., more-than-half, less-than-half), and then performed speeded verification on visual scenarios that displayed a proportion between 2 discrete quantities. We varied systematically not only the sentences, but also the visual materials, in order to study their effect on the verification process. Next, we used the same visual scenarios with analogous non-verbal probes that featured arithmetical inequality symbols (<, >). This manipulation enabled us to measure not only Polarity effects, but also, to compare the effect of different probe types (linguistic, non-linguistic) on processing. Like many previous studies, our results demonstrate that perceptual difficulty affects error rate and reaction time in keeping with Weber's Law. Interestingly, these performance parameters are also affected by the Polarity of the quantifiers used, despite the fact that sentences had the exact same meaning, sentence structure, number of words, syllables, and temporal structure. Moreover, an analogous contrast between the non-linguistic probes (<, >) had no effect on performance. Finally, we observed no interaction between performance parameters governed by Weber's Law and those affected by Polarity. We consider 4 possible accounts of the results (syntactic, semantic, pragmatic, frequency-based), and discuss their relative merit. PMID- 26142826 TI - Association of serum total bilirubin with renal outcome in Japanese patients with stages 3-5 chronic kidney disease. AB - OBJECTIVE: Serum bilirubin has been reported to be associated with the progression of kidney disease in patients with diabetic nephropathy. Less is known, however, about the relationship between bilirubin and chronic kidney disease (CKD) of other etiologies. This study was designed to clarify whether serum total bilirubin concentration is associated with kidney disease progression in patients with CKD independent of etiology. MATERIALS AND METHODS: This prospective observational study enrolled 279 consecutive patients with stages 3-5 CKD. The renal endpoint was the composite of the doubling of serum creatinine or end-stage renal disease requiring dialysis. Patients were divided into three groups by their serum total bilirubin concentrations: <=0.3 (lowest), 0.4-0.5 (middle), and >=0.6 (highest) mg/dL. A Cox proportional hazards model was applied to determine the risk factors for poor renal outcome. RESULTS: The median follow up period was 21months. One-hundred and three patients reached renal end points. After multivariable adjustment, a 0.1mg/dL increase in serum bilirubin was associated negatively with poor renal outcome (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60-0.87). In addition, after adjustment for confounding factors, including traditional and nontraditional cardiovascular risk factors, the middle (HR 3.14, 95% CI 1.36-8.57) and lowest (HR 4.22, 95% CI 1.81 11.59) bilirubin groups had significantly higher HRs for renal outcome than the highest bilirubin group. CONCLUSIONS: Lower serum bilirubin concentration was independently associated with adverse renal outcomes, suggesting that the measurement of serum bilirubin is useful for predicting kidney disease progression in patients with moderate to severe CKD. PMID- 26142827 TI - K(ATP) channel block prevents proteasome inhibitor-induced apoptosis in differentiated PC12 cells. AB - Dysfunction of the proteasome system has been suggested to be implicated in neuronal degeneration. Modulation of KATP channels appears to affect the viability of neuronal cells exposed to toxic insults. However, the effect of KATP channel blockers on the neuronal cell death mediated by proteasome inhibition has not been studied. The present study investigated the effect of KATP channel blockers on proteasome inhibitor-induced apoptosis in differentiated PC12 cells and SH-SY5Y cells. 5-Hydroxydecanoate (a selective KATP channel blocker) and glibenclamide (a cell surface and mitochondrial KATP channel inhibitor) reduced the proteasome inhibitor-induced apoptosis. Addition of the KATP channel blockers attenuated the proteasome inhibitor-induced changes in the levels of apoptosis related proteins, the loss of the mitochondrial transmembrane potential, the increase in the formation of reactive oxygen species and the depletion of glutathione in both cell lines. The results show that KATP channel blockers may attenuate proteasome inhibitor-induced apoptosis in PC12 cells by suppressing activation of the mitochondrial pathway and of the caspase-8- and Bid-dependent pathways. The preventive effect appears to be associated with the inhibition of the formation of reactive oxygen species and the depletion of glutathione. KATP channel blockade appears to prevent proteasome inhibition-induced neuronal cell death. PMID- 26142828 TI - Anti-fatigue effect of Myelophil in a chronic forced exercise mouse model. AB - This study was performed to evaluate the anti-fatigue effects of Myelophil. ICR male mice (10 weeks old) were forced to run for 1 hour, 5 days/week for 4 weeks. Each running session was followed by administration of distilled water, Myelophil (50 or 100 mg/kg), or ascorbic acid (100 mg/kg) 1h later. Equal proportions of Astragali Radix and Salviae Miltiorrhizae Radix were extracted using 30% ethanol, and formulated into Myelophil. To evaluate the anti-fatigue effects of Myelophil, exercise tolerance and forced swimming tests were conducted. Underlying mechanisms, including oxidant-antioxidant balance, inflammatory response, and energy metabolism, were investigated by analyzing skeletal muscle tissues and/or sera. Myelophil significantly increased exercise ability and latency times, and decreased the number of electric shocks and immobility time on exercise tolerance and forced swimming tests compared with control group. Myelophil also significantly ameliorated fatigue-induced alterations in oxidative stress biomarkers, antioxidant enzymes and antioxidant capacity, as measured by multiple assays, including enzyme activity assays and western blotting, as well as alterations in pro- and anti-inflammatory cytokines in skeletal muscle. Furthermore, Myelophil normalized alterations in energy metabolic markers in sera. These findings suggest that Myelophil reduces the effects of chronic fatigue, likely by attenuating oxidative and inflammatory responses and normalizing energy metabolism. Consequently, this study provides evidence for the clinical relevance of Myelophil. PMID- 26142829 TI - Biotinylated heptapeptides substituted with a D-amino acid as platelet-activating factor inhibitors. AB - Platelet-activating factor (PAF), a potent lipid mediator, is implicated in many inflammatory diseases, and therefore may serve as a direct target for anti inflammatory drugs. We previously reported that synthetic biotinylated peptides having a Tyr-Lys-Asp-Gly sequence markedly inhibit PAF-induced inflammation by direct binding, and that two synthetic fluorescence-labelled heptapeptides (Lys Trp-Tyr-Lys-Asp-Gly-Asp and D-Lys-Trp-Tyr-Lys-Asp-Gly-Asp) with high stability in plasma specifically bind to PAF-like lipids (oxidized- and lyso phosphatidylchoine). In this study, synthetic heptapeptides (Lys-Trp-Tyr-Lys-Asp Gly-Asp) coupled to a biotin molecule through the N-terminal amino group and epsilon-amino group of N-terminus Lys, (Btn)KP6 and K(Btn)P6, respectively, and their biotinylated peptides substituted with D-Lys at the N-terminus, (Btn)dKP6 and dK(Btn)P6, respectively, were investigated for their effects on PAF-induced inflammation. In the experiments using a rat model of hind paw oedema, (Btn)KP6, K(Btn)P6, (Btn)dKP6, and dK(Btn)P6 significantly inhibited PAF-induced paw oedema, with the highest inhibitory effect exhibited by dK(Btn)P6. The inhibitory effect of D-Tyr-D-Lys-D-Asp-Gly tetrapeptide on PAF-induced paw oedema was much lower than that of Tyr-Lys-Asp-Gly tetrapeptide. In the experiments using tryptophan fluorescence spectroscopy, (Btn)KP6, K(Btn)P6, (Btn)dKP6, and dK(Btn)P6 bound to PAF dose-dependently, with dK(Btn)P6 showing the strongest binding affinity, indicating that its affinity appears to be closely correlated with its inhibitory effect on PAF-induced inflammation. These results suggest that direct binding of (Btn)KP6, K(Btn)P6, (Btn)dKP6, and dK(Btn)P6 to PAF can lead to marked inhibition of PAF-induced inflammation, and these agents, particularly dK(Btn)P6, may be useful as anti-inflammatory drugs targeting PAF with high stability in plasma. PMID- 26142830 TI - Effect of rovatirelin, a novel thyrotropin-releasing hormone analog, on the central noradrenergic system. AB - Rovatirelin ([1-[-[(4S,5S)-(5-methyl-2-oxo oxazolidin-4-yl) carbonyl]-3-(thiazol 4-yl)-l-alanyl]-(2R)-2-methylpyrrolidine) is a novel synthetic agent that mimics the actions of thyrotropin-releasing hormone (TRH). The aim of this study was to investigate the electrophysiological and pharmacological effects of rovatirelin on the central noradrenergic system and to compare the results with those of another TRH mimetic agent, taltirelin, which is approved for the treatment of spinocerebellar degeneration (SCD) in Japan. Rovatirelin binds to the human TRH receptor with higher affinity (Ki=702nM) than taltirelin (Ki=3877nM). Rovatirelin increased the spontaneous firing of action potentials in the acutely isolated noradrenergic neurons of rat locus coeruleus (LC). The facilitatory action of rovatirelin on the firing rate in the LC neurons was inhibited by the TRH receptor antagonist, chlordiazepoxide. Reduction of the extracellular pH increased the spontaneous firing of LC neurons and rovatirelin failed to increase the firing frequency further, indicating an involvement of acid-sensitive K+ channels in the rovatirelin action. In in vivo studies, oral administration of rovatirelin increased both c-Fos expression in the LC and extracellular levels of noradrenaline (NA) in the medial prefrontal cortex (mPFC) of rats. Furthermore, rovatirelin increased locomotor activity. The increase in NA level and locomotor activity by rovatirelin was more potent and longer acting than those by taltirelin. These results indicate that rovatirelin exerts a central nervous system (CNS)-mediated action through the central noradrenergic system, which is more potent than taltirelin. Thus, rovatirelin may have an orally effective therapeutic potential in patients with SCD. PMID- 26142831 TI - Dermatoglyphic variation among the Limboo of Sikkim, India. AB - Variations in finger and palmar dermatoglyphic patterns are investigated among the Limboo (18-60 years, 150 males and 150 females), a little known population of Sikkim. The results for Limboo were compared with other North-East Indian populations. The most commonly occurring pattern was loop (males: 64.33%; females: 75.00%) followed by whorl (males: 31.00%; females: 21.33%) and finally arch (males: 4.67%; females: 3.66%). There were no significant differences between sexes in pattern types. The overall values of pattern intensity (P.I.I.), Dankmeijer's (D.I.) and Furuhata's (F.I.) indices were 14.08, 12.60 and 96.06 respectively. The P.I.I. was within the range for East Asian populations of North East India. The D.I. was similar to those reported for Rajbanshi, Kalita, Rabha and Newar populations, while F.I. was higher than in other populations of Eastern Himalaya and North-East India. The most frequently occurring mainline formulae in all palm prints (left and right combined) were 7.5'.5.- followed by 9.7.5.- and finally 11.9.7.- (p>0.05) and these were similar to the reported values for other North-eastern populations of India. The mean values of total finger ridge count (TFRC) and absolute finger ridge count (AFRC) were greater among males (138.03; s=42.26 and 198.78; s=77.4) than females (137.91; s=44.15 and 194.47; s=86.71). The a-b ridge count was greater among females than males. Sex differences in AFRC and a-b ridge count were both statistically significant (p<0.05). The mean TFRC values were within ranges for populations of North-East India. Cluster analysis based on P.I.I., D.I. and F.I. shows affinity of the Limbo to some of the populations of Assam and North-East India. PMID- 26142832 TI - Re: Anticoagulation and Antiplatelet Therapy in Urological Practice: ICUD/AUA Review Paper: D. J. Culkin, E. J. Exaire, D. Green, M. S. Soloway, A. J. Gross, M. R. Desai, J. R. White and D. J. Lightner J Urol 2014; 192: 1026-1034. PMID- 26142834 TI - Positive affect promotes well-being and alleviates depression: The mediating effect of attentional bias. AB - The present study tested whether the relationships among positive affect, psychological well-being, life satisfaction and depression could be explained by positive and negative attentional bias. Structural equation modeling and mediation analyses were conducted based on 565 medical freshmen in China. The model of attentional bias as a mediator between positive affect promoting well being and decreasing depression fit the data. Finding showed positive affect significantly related to positive and negative attentional biases. People who had higher level of positive affect held more positive attentional bias and less negative attentional bias, and reported higher levels of psychological well being, life satisfaction and lower levels of depression. The utility of the attentional bias as the mechanism through which positive affect enhances well being and alleviates depression was supported. Applications in cultivating positive affect and regulating attentional bias in counseling and education are discussed. PMID- 26142835 TI - Evaluation of auditory hallucinations in patients with schizophrenia: A validation study of the Malay version of Psychotic Symptom Rating Scales (PSYRATS). AB - The Psychotic Symptom Rating Scales (PSYRATS) is the most widely used validated scale to measure the specific symptoms of auditory hallucination and delusion. The aim of this study was to validate and to examine the psychometric properties of the auditory hallucination component of the Malay PSYRATS (MyPSYRATS). The research was done in the Universiti Kebangsaan Malaysia Medical Center (UKMMC) among 51 schizophrenia inpatients and outpatients who had experienced or reported verbal auditory hallucination. The psychometric properties of MyPSYRATS (auditory hallucination) were studied and a comparison was made between the psychometric properties obtained and the Positive and Negative Syndrome Scale (PANSS). The internal consistency of MyPSYRATS was good as revealed by Cronbach's alpha value. Factor analysis replicated three components (emotional, cognitive, and physical) similar to the factorial structure of the original auditory hallucination scale. However, two items were regrouped under the emotional component. Spearman's rank order correlation showed a significant positive relationship between the total score of auditory hallucinations and PANSS auditory hallucinations item (P3). In conclusion, the auditory hallucination domain of MyPSYRATS is a reliable and valid assessment tool for further clinical applications. PMID- 26142836 TI - Cerebrospinal fluid monoamine metabolite concentrations as intermediate phenotypes between glutamate-related genes and psychosis. AB - Glutamate-related genes have been associated with schizophrenia, but the results have been ambiguous and difficult to replicate. Homovanillic acid (HVA), 5 hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major degradation products of the monoamines dopamine, serotonin and noradrenaline, respectively, and their concentrations in the cerebrospinal fluid (CSF), mainly HVA, have been associated with schizophrenia. In the present study, we hypothesized that CSF HVA, 5-HIAA and MHPG concentrations represent intermediate phenotypes in the association between glutamate-related genes and psychosis. To test this hypothesis, we searched for association between 238 single nucleotide polymorphisms (SNPs) in ten genes shown to be directly or indirectly implicated in glutamate transmission and CSF HVA, 5-HIAA and MHPG concentrations in 74 patients with psychotic disease. Thirty-eight nominally significant associations were found. Further analyses in 111 healthy controls showed that 87% of the nominal associations were restricted to the patients with psychosis. Some of the psychosis-only-associated SNPs found in the d-amino acid oxidase activator (DAOA) and the kynurenine 3-monooxygenase (KMO) genes have previously been reported to be associated with schizophrenia. The present results suggest that CSF monoamine metabolite concentrations may represent intermediate phenotypes in the association between glutamate-related genes and psychosis. PMID- 26142837 TI - Forming implementation intentions improves prospective memory in early psychosis. AB - The study examined whether individuals with early psychosis are impaired in prospective memory (PM), that is, remembering to execute a planned intention in the future, and whether implementation intentions can improve their PM performance. Thirty participants with early psychosis and 33 healthy controls were randomly allocated to either an implementation intentions or control condition and completed a computerised event-based PM task. Participants were also administered two standardised tests of PM and an abbreviated IQ test. Results demonstrated that individuals with early psychosis showed PM deficits relative to healthy controls on the computerised PM task and on some standardised measures of PM. The PM performance of the early psychosis group benefited from forming implementation intentions. Implementation intentions was concluded to be an effective strategy for improving PM performance in individuals with early psychosis. PMID- 26142838 TI - Genotoxicity evaluation of the flavonoid, myricitrin, and its aglycone, myricetin. AB - Myricitrin, a flavonoid extracted from the fruit, leaves, and bark of Chinese bayberry (Myrica rubra SIEBOLD), is currently used as a flavor modifier in snack foods, dairy products, and beverages in Japan. Myricitrin is converted to myricetin by intestinal microflora; myricetin also occurs ubiquitously in plants and is consumed in fruits, vegetables, and beverages. The genotoxic potential of myricitrin and myricetin was evaluated in anticipation of worldwide marketing of food products containing myricitrin. In a bacterial reverse mutation assay, myricetin tested positive for frameshift mutations under metabolic activation conditions whereas myricitrin tested negative for mutagenic potential. Both myricitrin and myricetin induced micronuclei formation in human TK6 lymphoblastoid cells under conditions lacking metabolic activation; however, the negative response observed in the presence of metabolic activation suggests that rat liver S9 homogenate may detoxify reactive metabolites of these chemicals in mammalian cells. In 3-day combined micronucleus/Comet assays using male and female B6C3F1 mice, no induction of micronuclei was observed in peripheral blood, or conclusive evidence of damage detected in the liver, glandular stomach, or duodenum following exposure to myricitrin or myricetin. Our studies did not reveal evidence of genotoxic potential of myricitrin in vivo, supporting its safe use in food and beverages. PMID- 26142840 TI - Associations among solicitation, relationship quality, and adolescents' disclosure and secrecy with mothers and best friends. AB - Disclosure and secrecy with mothers and best friends about personal, bad behavior, and multifaceted (e.g., staying out late) activities were examined using daily diaries among 102 ethnically diverse, urban middle adolescents (M = 15.18 years, SD = .89). Adolescents disclosed more and kept fewer secrets from best friends than from mothers and more frequently disclosed and kept secrets about their personal than their bad behavior and multifaceted activities. Better daily relationship quality was associated with more disclosure about personal and multifaceted activities and less secrecy about bad behaviors for both mothers and best friends. Overall, when mothers solicited information, adolescents disclosed more but also kept more secrets from them, whereas best friends' solicitation was mostly associated with more disclosure. PMID- 26142839 TI - Fipronil induces CYP isoforms in rats. AB - The goal of the present study was to evaluate fipronil effects on the activities of drug metabolizing enzymes in rat liver microsomes. Rats were orally treated with fipronil at doses of 1, 5, 10 and 15 mg/kg bw/day for 6 days. Determinations of cytochrome P450 (CYP) enzyme activities were carried out in hepatic microsomes isolated from treated rats. The activities of some members of CYP2E, CYP1A, CYP2A, CYP2B and CYP3A subfamilies significantly increased after fipronil treatment in a dose-dependent manner as compared to control. The major effects were observed in the O-deethylation of ethoxyresorufin and O-demethylation of methoxyresorufin (reflecting CYP1A1/2 activities), in the O-depenthylation of pentoxyresorufin and 16beta-hydroxylation of testosterone (reflecting CYP2B1/2 activities), and in the N-demethylation of erythromycin and 6beta-hydroxylation of testosterone (reflecting CYP3A1/2 activities). Immunoblot studies revealed that fipronil increased the apoprotein levels of CYP1A1. Our results suggest that fipronil is an inducer of hepatic phase I CYP enzymes, causing an increased potential to interact with a wide range of xenobiotics or endogenous chemicals that are substrates of the CYP1A, CYP2B and CYP3A subfamilies. Further investigations are required to in vivo evaluate the potential of the metabolite fipronil sulfone as an inducer of phase I CYP enzymes. PMID- 26142841 TI - Growth, ruminal measurements, and health characteristics of Holstein bull calves fed an Aspergillus oryzae fermentation extract. AB - A fermentation extract of the fungus Aspergillus oryzae can be used as a prebiotic. The objective was to determine if dietary inclusion of a fermentation extract of A. oryzae as well as calf age would alter growth, health, performance parameters, and the growth and development of the rumen in Holstein calves from birth thru 1 wk postweaning; it was hypothesized that it would. Purchased bull calves (n=52) that originated from 1 of 13 farms were used in this experiment. All calves had serum IgG greater than 10 mg/mL. Calves were randomly assigned to a slaughter age, 4 (n=16) or 8 wk (n=36), and treatment, control (n=27) or fermentation extract of A. oryzae (AMF; n=25). Calves were housed and fed individually; no bedding was used and no forage was fed. Calves assigned to AMF were fed 2 g of AMF daily. Liquid AMF was delivered in milk replacer for the first 4 wk of the study; solid AMF was top-dressed on texturized starter thereafter. Calves were fed nonmedicated milk replacer twice daily (22.0% crude protein, 20.0% fat, dry matter basis; 680 g/d) and were weaned upon consumption of 0.91 kg of starter (20% crude protein, 2.0% fat; medicated with decoquinate) for 3 consecutive days or on d 45 of the study, whichever came first. Calves had ad libitum access to starter and water throughout the study. Feed intake as well as fecal and respiratory scores were recorded daily; body weight, withers height, and hip height were recorded weekly. Gross rumen measurements and rumen samples for future gross and histological analyses were taken at 4 and 8 wk. All calves grew similarly; weaning age averaged 40.39+/-0.77 d. Lifetime average daily gain was 0.60+/-0.05 kg/d and lifetime gain-to-feed ratio was 0.56+/-0.05. Milk replacer, starter, total dry matter intake, gross and histological rumen measurements, rumen pH, fecal and respiratory scores, and total medical costs were not affected by treatment. Despite total medical costs not differing by treatment, a lower percentage of AMF calves were treated for respiratory ailments and respiratory treatment cost was lower for AMF compared with control. Several factors may have contributed to an overall lack of observed treatment effect in this study, including include the use of a low-forage (compared with concentrate) diet, immunocompetent calves, and the selected product dose and routes of delivery. Dietary inclusion (2 g/d) of an extract of A. oryzae did not affect calf growth, intake, and ruminal or health measurements. PMID- 26142842 TI - Development and validation of a novel pedometer algorithm to quantify extended characteristics of the locomotor behavior of dairy cows. AB - Behavior is one of the most important indicators for assessing cattle health and well-being. The objective of this study was to develop and validate a novel algorithm to monitor locomotor behavior of loose-housed dairy cows based on the output of the RumiWatch pedometer (ITIN+HOCH GmbH, Futterungstechnik, Liestal, Switzerland). Data of locomotion were acquired by simultaneous pedometer measurements at a sampling rate of 10 Hz and video recordings for manual observation later. The study consisted of 3 independent experiments. Experiment 1 was carried out to develop and validate the algorithm for lying behavior, experiment 2 for walking and standing behavior, and experiment 3 for stride duration and stride length. The final version was validated, using the raw data, collected from cows not included in the development of the algorithm. Spearman correlation coefficients were calculated between accelerometer variables and respective data derived from the video recordings (gold standard). Dichotomous data were expressed as the proportion of correctly detected events, and the overall difference for continuous data was expressed as the relative measurement error. The proportions for correctly detected events or bouts were 1 for stand ups, lie downs, standing bouts, and lying bouts and 0.99 for walking bouts. The relative measurement error and Spearman correlation coefficient for lying time were 0.09% and 1; for standing time, 4.7% and 0.96; for walking time, 17.12% and 0.96; for number of strides, 6.23% and 0.98; for stride duration, 6.65% and 0.75; and for stride length, 11.92% and 0.81, respectively. The strong to very high correlations of the variables between visual observation and converted pedometer data indicate that the novel RumiWatch algorithm may markedly improve automated livestock management systems for efficient health monitoring of dairy cows. PMID- 26142843 TI - Effect of refrigerated storage on probiotic viability and the production and stability of antimutagenic and antioxidant peptides in yogurt supplemented with pineapple peel. AB - Fruit by-products are good resources of carbohydrates, proteins, vitamins, and minerals, which may function as growth nutrients for probiotic bacteria. This research aimed at evaluating effects of pineapple peel powder addition on the viability and activity of Lactobacillus acidophilus (ATCC 4356), Lactobacillus casei (ATCC393), and Lactobacillus paracasei ssp. paracasei (ATCC BAA52) in yogurts throughout storage at 4 degrees C for 28d. Plain and probiotic yogurts supplemented with or without pineapple peel powder or inulin were prepared. The probiotic counts in supplemented yogurts at 28d of storage ranged from 7.68 and 8.03 log cfu/g, one log cycle higher compared with nonsupplemented control yogurt. Degree of proteolysis in synbiotic yogurts was significantly higher than plain yogurts and increased substantially during storage. Crude water-soluble peptide extract of the probiotic yogurt with peel possessed stronger antimutagenic and antioxidant activities [evaluated measuring reducing power and scavenging capacity of 1,1-diphenyl-2-picrylhydrazyl; 2,2'-azino-bis(3-ethyl benzothiazoline-6-sulfonic acid), and hydroxyl radicals] than control and maintained during storage. Pineapple peel, a by-product of juice production, could be proposed as a prebiotic ingredient in the manufacture of yogurts with enhanced nutrition, and functionality. PMID- 26142844 TI - Five-day resynchronization programs in dairy cows including presynchronization and progesterone at two stages following artificial insemination. AB - Two experiments were conducted to assess pregnancy outcomes after a 5-d Ovsynch 56 Resynch program [RES; GnRH injection (d 0) 5 d before and 56 h after the first of 2 PG injections on d 5 and 6, and timed artificial insemination (TAI) on d 8] with or without a 5-d progesterone-releasing intravaginal controlled internal drug release (CIDR) insert applied at d 0. In experiment 1, nonpregnant cows were enrolled on d 35 post-AI: d-35 RES-CON (n=454) or d-35 RES-CIDR (n=495). Blood was collected on d 0 for progesterone assay. Only 76.4% of enrolled cows had high (>=1 ng/mL) progesterone on d-35 nonpregnant diagnoses (NPD). Pregnancy per AI (P/AI) diagnosed by transrectal palpation at 35 and 63 d post-TAI did not differ between treatments. An interaction between treatment and progesterone status on d 35 was detected. The d-35 RES-CIDR cows with progesterone >=1 ng/mL at treatment initiation had reduced P/AI compared with d-35 RES-CON (27.7 vs. 36.4%), whereas the opposite effect occurred for d-35 RES-CIDR cows with progesterone <1 ng/mL compared with d-35 RES-CON (39.5 vs. 31.7%). In experiment 2, cows were enrolled on d 31 post-AI (NPD): (1) d-31 PG-3-G-RES (n=208): Pre-PG on d 31, Pre-GnRH on d 34, and RES on d 41; (2) d-41 RES-CON (n=208); or (3) d-41 RES-CIDR (n=208) as in experiment 1, but starting on d 41. In a subset of cows (more than 102 per treatment), blood samples were collected for progesterone assay and ovarian structures were mapped by ultrasonography on d 31, 34, 41, 46, 48, and 55. Pregnancy was diagnosed by ultrasonography on d 31 and 78 post-TAI. The proportion of cows with progesterone >=1 ng/mL on d 31 was 70.6%. More d-31 PG-3 G-RES cows ovulated after Pre-GnRH (60.4%) than did d-41 RES-CON (16.5%) or d-41 RES-CIDR (9.3%) cows. More d-31 PG-3-G-RES cows had luteolysis after Pre-PG on d 31 (75.1%) than did d-41 RES-CON (7.5%) and d-41 RES-CIDR (8.6%) cows. Although more d-31 PG-3-G-RES cows were inseminated earlier, P/AI did not differ among treatments for cows inseminated after estrus or by TAI. Pregnancy per AI, however, was greater in cows starting RES on d 41 when progesterone was >=1 ng/mL compared with <1 ng/mL (44.8 vs. 31.6%), respectively. We conclude that presynchronization of estrous cycles in nonpregnant cows with PG and GnRH before a d-41 RES 5-d program does not improve P/AI. Furthermore, addition of the CIDR insert in a 5-d program decreased P/AI only when treatment was initiated in cows on d 35 post-AI and when progesterone was >=1 ng/mL (no corpus luteum) but not when beginning treatment on d 41. PMID- 26142845 TI - Apparent recovery of C18 polyunsaturated fatty acids from feed in cow milk: a meta-analysis of the importance of dietary fatty acids and feeding regimens in diets without fat supplementation. AB - A meta-analysis was conducted using the results of 82 experiments (78 publications, 266 treatments) to investigate the importance of dietary C18 fatty acids (FA) and feeding regimen for milk C18 FA profile and apparent recovery of selected FA relative to intake of these FA or their precursors. Feeding treatments based on lipid-supplemented diets were excluded. Feeding regimens were defined as grazing [including partial and full-time grazing, at dietary concentrate proportions from 0 to 44% dry matter (DM)], forage-based indoor feeding [>65% forage of total DM intake (DMI)], and concentrate-based indoor feeding (forage DMI <=65% of DMI). Linoleic acid (LLA), alpha-linolenic acid (ALA), and total C18 FA proportions in milk fat increased linearly with the respective dietary FA content in all feeding regimens tested. This effect was highest in the forage-based indoor feeding. Slopes were lowest for the grazing regimens, especially regarding ALA and the sum of all C18 FA, whereas the intercepts of the prediction equations of milk ALA and total C18 FA proportions were highest for grazing regimens. This indicates that, in grazing cows, factors other than dietary FA contents determine the C18 FA composition of the milk fat. At equal dietary LLA contents, the type of feeding regimen showed no significant effect on LLA proportion in milk fat. Milk fat proportions of rumenic acid and vaccenic acid were positively related to the sum of dietary ALA and LLA contents. Grazing regimens led to the strongest enrichment of rumenic acid and vaccenic acid in milk fat. The apparent recovery of ALA, LLA, and total C18 FA (secreted, % of intake), an estimate for transfer efficiency, decreased with increasing dietary content. This relationship followed a nonlinear decay function. When the dietary content of these FA exceeded a certain threshold (about 0.2, 0.8, and 2.8% of DM for ALA, LLA, and total C18 FA, respectively) the recovery in milk remained constant at about 5, 10, and 82% of the ingested ALA, LLA, and total C18 FA, respectively. At dietary proportions below 0.01% ALA and 1.5% total C18 FA of DM, their apparent recovery in milk fat exceeded 100%. In conclusion, a general inverse relationship between dietary C18 FA and the corresponding apparent recovery in milk fat seems to exist. Within this frame, the effect of different types of feeding regimens on the eventual milk C18 FA profile varies. Among them, grazing pasture appears to provide the most variable properties. PMID- 26142846 TI - Microbial cell-free extracts as sources of enzyme activities to be used for enhancement flavor development of ewe milk cheese. AB - Freeze-dried cell-free extracts (CFE) from Lactobacillus casei LC01, Weissella cibaria 1XF5, Hafnia alvei Moller ATCC 51815, and Debaryomyces hansenii LCF-558 were used as sources of enzyme activities for conditioning the ripening of ewe milk cheese. Compared with control cheese (CC), CFE did not affect the gross composition and the growth of the main microbial groups of the cheeses. As shown through urea-PAGE electrophoresis of the pH 4.6-soluble nitrogen fraction and the analysis of free AA, the secondary proteolysis of the cheeses with CFE added was markedly differed from that of the CC. Compared with CC, several enzyme activities were higher in the water-soluble extracts from cheeses made with CFE. In agreement, the levels of 49 volatile compounds significantly differentiated CC from the cheeses made with CFE. The level of some alcohols, ketones, sulfur compounds, and furans were the lowest in the CC, whereas most aldehydes were the highest. Each CFE seemed to affect a specific class of chemical compounds (e.g., the CFE from H. alvei ATCC 51815 mainly influenced the synthesis of sulfur compounds). Apart from the microbial source used, the cheeses with the addition of CFE showed higher score for acceptability than the control cheese. Cheese ripening was accelerated or conditioned using CFE as sources of tailored enzyme activities. PMID- 26142847 TI - The Cornell Net Carbohydrate and Protein System: Updates to the model and evaluation of version 6.5. AB - New laboratory and animal sampling methods and data have been generated over the last 10 yr that had the potential to improve the predictions for energy, protein, and AA supply and requirements in the Cornell Net Carbohydrate and Protein System (CNCPS). The objectives of this study were to describe updates to the CNCPS and evaluate model performance against both literature and on-farm data. The changes to the feed library were significant and are reported in a separate manuscript. Degradation rates of protein and carbohydrate fractions were adjusted according to new fractionation schemes, and corresponding changes to equations used to calculate rumen outflows and postrumen digestion were presented. In response to the feed-library changes and an increased supply of essential AA because of updated contents of AA, a combined efficiency of use was adopted in place of separate calculations for maintenance and lactation to better represent the biology of the cow. Four different data sets were developed to evaluate Lys and Met requirements, rumen N balance, and milk yield predictions. In total 99 peer reviewed studies with 389 treatments and 15 regional farms with 50 different diets were included. The broken-line model with plateau was used to identify the concentration of Lys and Met that maximizes milk protein yield and content. Results suggested concentrations of 7.00 and 2.60% of metabolizable protein (MP) for Lys and Met, respectively, for maximal protein yield and 6.77 and 2.85% of MP for Lys and Met, respectively, for maximal protein content. Updated AA concentrations were numerically higher for Lys and 11 to 18% higher for Met compared with CNCPS v6.0, and this is attributed to the increased content of Met and Lys in feeds that were previously incorrectly analyzed and described. The prediction of postruminal flows of N and milk yield were evaluated using the correlation coefficient from the BLUP (R(2)BLUP) procedure or model predictions (R(2)MDP) and the concordance correlation coefficient. The accuracy and precision of rumen-degradable N and undegradable N and bacterial N flows were improved with reduced bias. The CNCPS v6.5 predicted accurate and precise milk yield according to the first-limiting nutrient (MP or metabolizable energy) with a R(2)BLUP=0.97, R(2)MDP=0.78, and concordance correlation coefficient=0.83. Furthermore, MP allowable milk was predicted with greater precision than metabolizable energy allowable milk (R(2)MDP=0.82 and 0.76, respectively, for MP and metabolizable energy). Results suggest a significant improvement of the model, especially under conditions of MP limitation. PMID- 26142848 TI - Updating the Cornell Net Carbohydrate and Protein System feed library and analyzing model sensitivity to feed inputs. AB - The Cornell Net Carbohydrate and Protein System (CNCPS) is a nutritional model that evaluates the environmental and nutritional resources available in an animal production system and enables the formulation of diets that closely match the predicted animal requirements. The model includes a library of approximately 800 different ingredients that provide the platform for describing the chemical composition of the diet to be formulated. Each feed in the feed library was evaluated against data from 2 commercial laboratories and updated when required to enable more precise predictions of dietary energy and protein supply. A multistep approach was developed to predict uncertain values using linear regression, matrix regression, and optimization. The approach provided an efficient and repeatable way of evaluating and refining the composition of a large number of different feeds against commercially generated data similar to that used by CNCPS users on a daily basis. The protein A fraction in the CNCPS, formerly classified as nonprotein nitrogen, was reclassified to ammonia for ease and availability of analysis and to provide a better prediction of the contribution of metabolizable protein from free AA and small peptides. Amino acid profiles were updated using contemporary data sets and now represent the profile of AA in the whole feed rather than the insoluble residue. Model sensitivity to variation in feed library inputs was investigated using Monte Carlo simulation. Results showed the prediction of metabolizable energy was most sensitive to variation in feed chemistry and fractionation, whereas predictions of metabolizable protein were most sensitive to variation in digestion rates. Regular laboratory analysis of samples taken on-farm remains the recommended approach to characterizing the chemical components of feeds in a ration. However, updates to the CNCPS feed library provide a database of ingredients that are consistent with current feed chemistry information and laboratory methods and can be used as a platform to formulate rations and improve the description of biology within the model. PMID- 26142849 TI - Effect of yogurt containing deep sea water on health-related serum parameters and intestinal microbiota in mice. AB - Deep sea water (DSW) has health benefits and is widely used as food supplement; however, its effect in fermented products has not been explored. Here, we investigated the effect of DSW-containing yogurt on health-related serum parameters and intestinal microbiota in mice. Animals were assigned to 3 feeding groups, which received water (control), normal yogurt (N-yogurt), or DSW containing yogurt (DSW-yogurt) with a basal diet. Mice were killed at wk 4 or 8 of feeding and analyzed for serum parameters and microbial population in the small intestine. Both yogurt groups demonstrated increased populations of intestinal lactic acid bacteria compared with the control group. The activity of serum aspartate aminotransferase and alanine aminotransferase was markedly decreased in the DSW-yogurt and N-yogurt groups, and triglyceride level tended to be lower in the DSW-yogurt group compared with that in the control mice. Furthermore, the DSW-yogurt group showed a more significant decrease in the ratio of total cholesterol to high-density lipoprotein-cholesterol than did the N yogurt group. These findings suggest that DSW supplementation of yogurt can increase its beneficial effects on lipid metabolism. PMID- 26142850 TI - Genetic relationships between claw health traits of dairy cows in different parities, lactation stages, and herds with different claw disorder frequencies. AB - Claw disorders affect cow welfare and profitability of farms. Not only claw disorders but also the need for trimming, known as trimming status, has been shown to be heritable. Limited knowledge is available on whether claw health traits (claw disorders and trimming status) are genetically the same trait in different parities, lactation stages, or in herds with low or high frequency of claw disorders. The aim of the current study was to estimate frequencies, heritabilities, and genetic correlations of claw health traits measured in different parities (first vs. later parities), in different lactation stages (early vs. late lactation), and in herds with different frequencies of claw disorders (low vs. high frequency). Analyses revealed that heritabilities measured in different parities, lactation stages, or herds with different trait frequencies are similar for most claw health traits. Also, genetic correlations (rg) for most claw health traits were not found to be different from unity for traits in different parities, lactation stages, or herds with different trait frequencies. Sole hemorrhage and infectious lesions were genetically different traits in first or later parities (rg=0.29+/-0.31 and 0.66+/-0.15, respectively). White line separation and infectious lesions were genetically different in early and late lactation (rg=0.53+/-0.20 and 0.69+/-0.13, respectively), and sole ulcer was genetically different in herds with low or high frequency of sole ulcer (rg=0.75+/-0.14). In our analysis, we did not find convincing evidence to supports the use of multiple trait models for the analysis of claw health traits treating them as different traits in different parities, lactation stages, and herds with different claw disorder frequency. PMID- 26142851 TI - Weaning age affects growth, feed intake, gastrointestinal development, and behavior in Holstein calves fed an elevated plane of nutrition during the preweaning stage. AB - Recent research has revealed potential advantages of feeding an elevated plane of nutrition to calves during the preweaning period. However, calves fed more nutrients preweaning may be more susceptible to depressed growth and weaning stress during the transition from liquid to solid feed. The objective of this study was to investigate the relationship between the age of weaning and feed intake, and its influence on growth, gastrointestinal development, and behavioral indicators in dairy calves fed an elevated plane of nutrition during the preweaning period. To meet this objective, 20 female Holstein calves were randomly assigned at birth to be weaned at 6 or 8 wk. Milk replacer (mixed at 150 g/L) was offered at 1.2 kg/calf per day in 2 meals until a 1-wk step-down, when meals were reduced by 50% 1 wk before weaning. Daily starter, chopped oat straw, water intake, and weekly body weights were measured until d 70 of life. To assess digestive tract development, rumen fluid, fecal, and blood samples were taken before and after weaning (d 35, 49, and 63) and analyzed for ruminal short-chain fatty acids, blood beta-hydroxybutyrate, and fecal starch, respectively. Behavioral indicators of weaning stress, including vocalizing and non-nutritive oral behavior, were measured by visual observation for 1 h, 3 times per week, before the second feeding of the day during the period from 2 wk before weaning to 2 wk after weaning. The calves weaned at 8 wk compared with 6 wk had higher average daily gain for the week preweaning (0.79+/-0.09 vs. 0.34+/-0.10 kg/d) and postweaning (1.05+/-0.09 vs. 0.35+/-0.11 kg/d), and were heavier at d 70 (99.9+/ 1.81 vs. 91.0+/-2.26 kg). From 5 to 8 wk of age, starter and water intakes were lower in calves weaned at 8 wk of age. However, overall starter intake did not differ during the last week of the experiment. Furthermore, calves weaned at 8 wk compared with 6 wk had higher starter intake for 1 wk preweaning (1.36+/-0.13 vs. 0.40+/-0.08 kg/d) and postweaning (2.51+/-0.20 vs. 1.16+/-0.15 kg/d). In both treatments, weaning increased ruminal short-chain fatty acids, blood beta hydroxybutyrate, and fecal starch, yet the differences between the week before and after weaning were greater for calves weaned at 6 wk compared with those weaned at 8 wk. Treatment * week relative to weaning interactions indicated that several behaviors varied between early- and later-weaned calves during the week before weaning; calves weaned at 6 wk tended to exhibit 75% more non-nutritive oral behavior and spent 55% less time ruminating, and 36% less time lying compared with calves weaned at 8 wk. Under the conditions of this study, the results suggest that calves fed an elevated plane of nutrition preweaning have higher starter intakes and average daily gain during the weaning period when weaning is extended from 6 to 8 wk of age. PMID- 26142852 TI - Effects of cultivar and grazing initiation date on fall-grown oat for replacement dairy heifers. AB - Fall-grown oat has shown promise for extending the grazing season in Wisconsin, but the optimum date for initiating grazing has not been evaluated. Our objectives for this project were (1) to assess the pasture productivity and nutritive value of 2 oat cultivars [Ogle and ForagePlus (OG and FP, respectively)] with late-September (EG) or mid-October (LG) grazing initiation dates; and (2) to evaluate growth performance by heifers grazing these oat forages compared with heifers reared in confinement (CON). A total of 160 gravid Holstein heifers (80 heifers/yr) were assigned to 10 research groups (8 heifers/group). Mean initial body weight was 509+/-40.5 kg in 2013 and 517+/-30.2 kg in 2014. Heifer groups were assigned to specific pastures arranged as a 2*2 factorial of oat cultivars and grazing initiation dates. Grazing heifer groups were allowed to strip-graze oat pastures for 6 h daily before returning to the barn, where they were offered a forage-based basal total mixed ration. Main effects of oat cultivar and sampling date interacted for forage characteristics in 2013, but not in 2014. During 2013, oat forage mass increased until early November before declining in response to freezing weather conditions, thereby exhibiting linear and quadratic effects of sampling date, regardless of oat cultivar. Similar trends over time were observed in 2014. For 2013, the maximum forage mass was 5,329 and 5,046 kg/ha for FP and OG, respectively, whereas the mean maximum forage mass for 2014 was 4,806 kg/ha. ForagePlus did not reach the boot stage of growth during either year of the trial; OG matured more rapidly, reaching the late-heading stage during 2013, but exhibited only minor maturity differences from FP in 2014. For 2013, average daily gain for CON did not differ from grazing heifer groups (overall mean=0.63 kg/d); however, average daily gain from FP was greater than OG (0.68 vs. 0.57 kg/d), and greater from EG compared with LG (0.82 vs. 0.43 kg/d). For 2013, advantages in average daily gain for heifers grazing FP pastures were likely related to the greater energy density of FP oat throughout the fall that reached a maximum of 68.8% total digestible nutrients on November 27 compared with only 63.7% for OG on October 10. During 2014, average daily gain from CON exceeded all grazing heifer groups (0.81 vs. 0.57 kg/d), and average daily gain from EG again exceeded LG (0.70 vs. 0.44 kg/d). These results suggest that delaying grazing until mid-October will consistently suppress heifer growth performance, particularly if rapidly maturing cultivars are used. PMID- 26142855 TI - Effects of the DGAT1 polymorphism on test-day milk production traits throughout lactation. AB - Several studies have shown that the diacylglycerol O-acyltransferase 1 (DGAT1) K232A polymorphism has a major effect on milk production traits. It is less clear how effects of DGAT1 on milk production traits change throughout lactation, if dominance effects of DGAT1 are relevant, and whether DGAT1 also affects lactose content, lactose yield, and total energy output in milk. Results from this study, using test-day records of 3 subsequent parities of around 1,800 cows, confirm previously reported effects of the DGAT1 polymorphism on milk, fat, and protein yield, as well as fat and protein content. In addition, we found significant effects of the DGAT1 polymorphism on lactose content and lactose yield. No significant effects on somatic cell score were detected. The effect of DGAT1 on total energy excreted in milk was only significant in parity 1 and is mainly due to a higher energy output in milk of heterozygous cows. Significant but relatively small dominance effects of DGAT1 on fat content and yield were detected, which are of little practical relevance. Significant DGAT1 by lactation stage interaction was detected for milk yield, lactose yield, fat content, and protein content, indicating that the effect of the DGAT1 polymorphism changes during lactation. In general, the DGAT1 effect shows a large increase during early lactation (from the start of lactation to d 50 to 150) and tends to decrease later in lactation. No DGAT1 by lactation stage interaction for fat yield was observed. Similar to DGAT1, effects of other genes also might vary throughout lactation and, therefore, using longitudinal models is recommended. PMID- 26142853 TI - In vitro probiotic characteristics of Lactobacillus plantarum ZDY 2013 and its modulatory effect on gut microbiota of mice. AB - Lactobacillus plantarum ZDY 2013, a novel strain isolated from Chinese traditional fermented acid beans, was systematically evaluated for its survival capacity under stress conditions (pH, bile salt, simulated gastrointestinal tract, and antibiotics), production of exopolysaccharide and antagonism against 8 pathogens. Its effect on mice gut microbiota was also investigated by quantitative PCR and PCR-denaturing gradient gel electrophoresis. The results showed that ZDY 2013 can grow at pH 3.5 and survive at pH 2.0 for 6 h and at 0.45% bile salt for 3 h. The exopolysaccharide yield was up to 204+/-7.68 mg/L. The survival rate of ZDY 2013 in a simulated gastrointestinal tract was as high as 65.84%. Antagonism test with a supernatant of ZDY 2013 showed maximum halo of 28 mm against Listeria monocytogenes. The inhibition order was as follows: Listeria monocytogenes, Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, Shigella sonnei, Enterobacter sakazakii, and Staphylococcus aureus. Lactobacillus plantarum ZDY 2013 was sensitive to some antibiotics (e.g., macrolide, sulfonamides, aminoglycoside, tetracyclines and beta-lactams), whereas it was resistant to glycopeptides, quinolones, and cephalosporins antibiotics. Denaturing gradient gel electrophoresis profile demonstrated that ZDY 2013 administration altered the composition of the microbiota at various intestinal loci of the mice. Moreover, the quantitative PCR test showed that the administration of ZDY 2013 enhanced the populations of Bifidobacterium and Lactobacillus in either the colon or cecum, and reduced the potential enteropathogenic bacteria (e.g., Enterococcus, Enterobacterium, and Clostridium perfringens). Lactobacillus plantarum ZDY 2013 exhibited high resistance against low pH, bile salt, and gastrointestinal fluid, and possessed antibacterial and gut microbiota modulation properties with a potential application in the development of dairy food and nutraceuticals. PMID- 26142854 TI - Suitability of capillary blood obtained by a minimally invasive lancet technique to detect subclinical ketosis in dairy cows by using 3 different electronic hand held devices. AB - The objective of this study was to evaluate the suitability of capillary blood obtained by a minimally invasive lancet technique to detect subclinical ketosis in 49 prepartum and 191 postpartum Holstein-Friesian cows using 3 different electronic hand-held devices [FreeStyle Precision (FSP, Abbott), GlucoMen LX Plus (GLX, A. Menarini), NovaVet (NOV, Nova Biomedical)]. The beta-hydroxybutyrate (BHBA) concentration in serum harvested from coccygeal blood samples was analyzed in a laboratory and used as a reference value. Capillary samples were obtained from the skin of the exterior vulva by using 1 of 3 different lancets. In all samples, the concentration of BHBA was immediately analyzed with all 3 hand-held devices used in random order. All lancets used in the study were eligible for capillary blood collection but differed in the total number of incisions needed. Spearman correlation coefficients between the BHBA concentrations in capillary blood and the reference test were highly significant with 83% for the FSP, 73% for the NOV, and 63% for the GLX. Using capillary blood, the FSP overestimated the mean BHBA concentration compared with the reference test (+0.08 mmol/L), whereas the GLX and NOV underestimated the mean concentration (-0.07 and -0.01 mmol/L). When a BHBA concentration of 1.2 mmol/L in serum was used to define subclinical ketosis, the corresponding analyses of receiver operating characteristics resulted in optimized thresholds for capillary blood of 1.1 mmol/L for the NOV and GLX devices, and of 1.0 mmol/L for the FSP. Based on these thresholds, sensitivities (Se) and specificities (Sp) were 89 and 84% for the NOV, 80 and 89% for the GLX, and 100 and 76% for the FSP. Based on a serum BHBA concentration of 1.4 mmol/L, analyses of receiver operating characteristics resulted in optimized cut-offs of 1.4 mmol/L for the FSP (Se 100%, Sp 92%), 1.3 mmol/L for the NOV (Se 80%, Sp 95%), and 1.1 mmol/L (Se 90%, Sp 85%) for the GLX. Using these optimized thresholds for the specific hand-held meters, no significant differences between the devices in Se and Sp to detect subclinical ketosis in coccygeal blood were observed. Calculated test characteristics for analyzing capillary blood using the hand-held devices were numerically smaller compared with blood obtained from a coccygeal vessel, but overlapping confidence intervals indicate no statistical difference between the origin of the sample. Hence, this procedure seems to be suitable for ketosis monitoring in dairy cows, but further validation with more data from different farms is recommended. PMID- 26142856 TI - Characterization of microRNA in bovine in vitro culture media associated with embryo quality and development. AB - Dairy cattle fertility has declined over time due to factors including reduced fertilization and early embryonic loss. To counter fertility problems and better study preimplantation embryonic development, in vitro production systems have been developed. These systems largely assess embryos based on their morphology, which is not a strong indicator of developmental potential. Currently, no biomarkers can be used to noninvasively survey an embryo's potential in terms of its development and ability to establish a pregnancy. Thus, the objective of this study was to characterize and identify microRNA (miRNA) in culture media of embryos of differing developmental competence for future development as noninvasive biomarkers of embryo quality. The MiRNA sequencing of media conditioned by blastocyst and degenerate (those that failed to develop from the morula to blastocyst stage) embryos, revealed 11 differentially expressed miRNA; all were higher in concentration in degenerate conditioned media. Differential expression of mature microRNA (miR)-24, miR-191, and miR-148a was further validated using quantitative real-time PCR. Functional analysis of miR-24 revealed that addition of a mimic miRNA to culture media of morulae embryos resulted in a 27.3% decrease in development to the blastocyst stage. Furthermore, expression of miR-24 was 44.29-fold higher in blastocysts cultured with a miR-24 mimic compared with control blastocysts. Interestingly, the expression of CDKN1b, a target gene of miR-24 was repressed in embryos grown in the presence of the miRNA mimic. Mimic supplementation experiments suggest that miRNA are taken up by the embryo and that extracellular miRNA affect embryonic development. Overall, identification of a rich extracellular milieu in conditioned media sets the framework for future studies to determine the long-term predictive ability of embryo-based miRNA biomarkers on pregnancy outcome. PMID- 26142857 TI - Stability of nonfouling electroless nickel-polytetrafluoroethylene coatings after exposure to commercial dairy equipment sanitizers. AB - Application of nonfouling coatings on thermal processing equipment can improve operational efficiency. However, to enable effective commercial translation, a need exists for more comprehensive studies on the stability of nonfouling coatings after exposure to different sanitizers. In the current study, the influence of different commercial dairy equipment sanitizers on the nonfouling properties of stainless steel modified with electroless Ni polytetrafluoroethylene (PTFE) coatings was determined. Surface properties, such as dynamic contact angle, surface energy, surface morphology, and elemental composition, were measured before and after the coupons were exposed to the sanitizers for 168 cleaning cycles. The fouling behavior of Ni-PTFE-modified stainless steel coupons after exposure was also evaluated by processing raw milk on a self-fabricated benchtop-scale plate heat exchanger. The results indicated that peroxide sanitizer had only minor effect on the Ni-PTFE-modified stainless steel surface, whereas chlorine- and iodine-based sanitizers influenced the surface properties drastically. The coupons after 168 cycles of exposure to peroxide sanitizer accumulated the least amount of fouling material (4.44+/ 0.24mg/cm(2)) compared with the coupons exposed to the other 3 sanitizers. These observations indicated that the Ni-PTFE nonfouling coating retained antifouling properties after 168 cycles of exposure to peroxide-based sanitizer, supporting their potential application as nonfouling coatings for stainless steel dairy processing equipment. PMID- 26142858 TI - Prediction of process cheese instrumental texture and melting characteristics using dielectric spectroscopy and chemometrics. AB - This study evaluated the potentiality of dielectric spectroscopy as a tool to predict the functional properties of process cheese. Dielectric properties of process cheese were collected over the frequency range 0.2 to 3.2GHz at 25 degrees C. Dielectric spectra of process cheese were collected using a high temperature, open-ended dielectric probe connected to a vector network analyzer. The present study was conducted using 2 sets of commercial process cheese formulations and a set of specially formulated process cheese. For the all the process cheese samples analyzed, a decrease in dielectric constant and dielectric loss factor was observed as the incident frequency increased. Partial least square regression (PLSR) and multilayer perceptron neural network models were developed using the dielectric spectra of process cheese to predict the hardness (gf), melting point ( degrees C), and modified Schreiber melt diameter (mm) of process cheese. The prediction models were validated using the full cross validation method. The ratio of prediction error to deviation was greater than 2 for melt diameter and hardness, indicating a good practical utility of the PLSR prediction models. The predictability of multilayer perceptron neural network was less than the PLSR models and could be due to the small number of training samples in the data sets. Dielectric spectroscopy coupled with PLSR could be a useful tool for the nondestructive measurement of functional properties of process cheese. PMID- 26142859 TI - Evaluation of genomic selection for replacement strategies using selection index theory. AB - Our objective was to investigate the economic effect of prioritizing heifers for replacement at the herd level based on genomic estimated breeding values, and to compute break-even genotyping costs across a wide range of scenarios. Specifically, we aimed to determine the optimal proportion of preselection based on parent average information for all scenarios considered. Considered replacement strategies include a range of different selection intensities by considering different numbers of heifers available for replacement (15-45 in a herd with 100 dairy cows) as well as different replacement rates (15-40%). Use of conventional versus sexed semen was considered, where the latter resulted in having twice as many heifers available for replacement. The baseline scenario relies on prioritization of replacement heifers based on parent average. The first alternative scenario involved genomic selection of heifers, considering that all heifers were genotyped. The benefits of genomic selection in this scenario were computed using a simple formula that only requires the number of lactating animals, the difference in accuracy between parent average and genomic selection (GS), and the selection intensity as input. When all heifers were genotyped, using GS for replacement of heifers was beneficial in most scenarios for current genotyping prices, provided some room exists for selection, in the sense that at least 2 more heifers are available than needed for replacement. In those scenarios, minimum break-even genotyping costs were equal to half the economic value of a standard deviation of the breeding goal. The second alternative scenario involved a preselection based on parent average, followed by GS among all the preselected heifers. It was in almost all cases beneficial to genotype all heifers when conventional semen was used (i.e., to do no preselection). The optimal proportion of preselection based on parent average was at least 0.63 when sexed semen was used. Use of sexed semen increased the potential benefit of using GS, because it increased the room for selection. Critical assumptions that should not be ignored when calculating the benefit of GS are (1) a decrease in replacement rate can only be achieved by increasing productive life in the herd, and (2) accuracies of selection should be used rather than accuracies of estimated breeding values based on the prediction error variance and base-generation genetic variance, because the latter lead to underestimation of the potential of GS. PMID- 26142860 TI - The effects of firocoxib on cautery disbudding pain and stress responses in preweaned dairy calves. AB - Perioperative analgesic effects of oral firocoxib following cautery disbudding were investigated in preweaned calves. Twenty Holstein calves approximately 4 to 6wk old received a single oral dose of firocoxib, a nonsteroidal antiinflammatory, at 0.5mg/kg (n=10) or placebo (n=10) in a randomized controlled clinical trial. Responses, including ocular temperature determined by infrared thermography, pressure algometry measuring mechanical nociception threshold, and heart rate, were evaluated at 2, 4, 7, 8, and 24h after cornual nerve block and cautery disbudding. Blood samples were collected over 96h and analyzed for plasma cortisol and substance P concentrations by RIA. Additionally, ex vivo prostaglandin E2 concentrations were determined over a 72-h study period using an enzyme immunoassay. Data were analyzed using a linear mixed effects model with repeated measures. An inhibition of ex vivo prostaglandin E2 synthesis was observed from 12 to 48h following disbudding in calves treated with firocoxib. Cautery disbudding was associated with an increased nociception for the duration of sampling (24h). During the initial 24-h period following disbudding, no difference in response between treatment groups was noted. Following 24h, mean cortisol concentrations diverged between the 2 study groups with placebo-treated calves having increased cortisol concentrations at approximately 48h after disbudding. Furthermore, the overall integrated cortisol response as calculated as area under the effect curve tended to be reduced in firocoxib-treated calves. The prolonged effects of cautery dehorning require further investigation. Moreover, the effect of firocoxib on cortisol reduction observed in this study requires additional exploration. PMID- 26142861 TI - Concentrations of luteinizing hormone and ovulatory responses in dairy cows before timed artificial insemination. AB - The objective was to determine the incidence of LH surges and ovulatory responses in lactating dairy cows enrolled in a timed artificial insemination (TAI) program. Cows were assigned randomly to 2 presynchronization treatments: (1) Pre10 (n=37): 2 injections of PGF2alpha (PG; PG-1 and PG-2) 14 d apart (Presynch); or (2) PG-3-G (n=33): one 25-mg injection of PG (Pre-PG) administered 3 d before a 100-ug GnRH injection (Pre-GnRH). Ten days after PG-2 or Pre-PG, all cows were enrolled in a 7-d Ovsynch TAI program [injection of GnRH (GnRH-1) 7 d before PG (PG-3) and GnRH (GnRH-2) administered at either 56 or 72 h after PG-3; TAI at 72 h]. Blood was collected to determine LH at (1) Pre-GnRH: 48 to 80 h after PG-2 and hourly from 72 to 78 h (Pre-GnRH at 72 h); (2) GnRH-1: 0 to 6 h after GnRH-1; and (3) GnRH-2: 48 to 80 h after PG-3 and hourly from 56 to 62 h or 72 to 78 h for cows injected with GnRH-2 at 56 or 72 h after PG-3, respectively. Ovaries were scanned and pregnancy per TAI (P/AI) was diagnosed 31 and 61 d post TAI by transrectal ultrasonography. The Pre-GnRH injection increased the incidences of LH surges (100 vs. 43%) and ovulation (91 vs. 60%) and subsequent concentrations of progesterone in PG-3-G cows compared with Pre10 cows, respectively. Seven days later, incidence of ovulation (48 to 62%) and occurrence of LH surges (100%) did not differ between treatments after GnRH-1. In contrast, LH concentrations and area under the LH curve of Pre10 cows were greater than that of PG-3-G cows because progesterone was greater in PG-3-G than in Pre10 cows (4.6+/-0.4 vs. 2.8+/-0.4 ng/mL), respectively. Concentrations of LH did not differ after GnRH-2 at either 56 or 72 h; however, 1 cow receiving GnRH-2 at 56 h and 3 cows at 72 h had early spontaneous LH surges before GnRH-2. Ovulation was suppressed overall in 210 blood collection windows in cows with elevated progesterone concentrations. When progesterone was <1 ng/mL after either PG-2 or PG-3 injections, GnRH-induced LH surges occurred in more than 90% of cows, and incidence of ovulation exceeded 80%. Pregnancy per AI tended to differ for PG-3-G (56.7%) compared with Pre10 (37.8%) and for 56 h (54.5%) compared with 72 h (38.2%), with the Pre10-72 h treatment combination producing less than half (22.2%) the pregnancies compared with all other treatment combinations. Furthermore, in these same cows, post-TAI luteal tissue volume tended to be compromised. We conclude that incidences of GnRH-induced LH surges and ovulation are suppressed in cows with elevated progesterone, possibly contributing to some loss in P/AI in TAI programs. PMID- 26142862 TI - Nano spray-dried sodium chloride and its effects on the microbiological and sensory characteristics of surface-salted cheese crackers. AB - Reducing particle size of salt to approximately 1.5 um would increase its surface area, leading to increased dissolution rate in saliva and more efficient transfer of ions to taste buds, and hence, perhaps, a saltier perception of foods. This has a potential for reducing the salt level in surface-salted foods. Our objective was to develop a salt using a nano spray-drying method, to use the developed nano spray-dried salt in surface-salted cheese cracker manufacture, and to evaluate the microbiological and sensory characteristics of cheese crackers. Sodium chloride solution (3% wt/wt) was sprayed through a nano spray dryer. Particle sizes were determined by dynamic light scattering, and particle shapes were observed by scanning electron microscopy. Approximately 80% of the salt particles produced by the nano spray dryer, when drying a 3% (wt/wt) salt solution, were between 500 and 1,900 nm. Cheese cracker treatments consisted of 3 different salt sizes: regular salt with an average particle size of 1,500 um; a commercially available Microsized 95 Extra Fine Salt (Cargill Salt, Minneapolis, MN) with an average particle size of 15 um; and nano spray-dried salt with an average particle size of 1.5 um, manufactured in our laboratory and 3 different salt concentrations (1, 1.5, and 2% wt/wt). A balanced incomplete block design was used to conduct consumer analysis of cheese crackers with nano spray-dried salt (1, 1.5, and 2%), Microsized salt (1, 1.5, and 2%) and regular 2% (control, as used by industry) using 476 participants at 1wk and 4mo. At 4mo, nano spray dried salt treatments (1, 1.5, and 2%) had significantly higher preferred saltiness scores than the control (regular 2%). Also, at 4mo, nano spray-dried salt (1.5 and 2%) had significantly more just-about-right saltiness scores than control (regular 2%). Consumers' purchase intent increased by 25% for the nano spray-dried salt at 1.5% after they were notified about the 25% reduction in sodium content of the cheese cracker. We detected significantly lower yeast counts for nano spray-dried salt treatments (1, 1.5, and 2%) at 4mo compared with control (regular) salt (1, 1.5 and 2%). We detected no mold growth in any of the treatments at any time. At 4mo, we found no significant differences in sensory color, aroma, crunchiness, overall liking, or acceptability scores of cheese crackers using 1.5 and 1% nano spray-dried salt compared with control. Therefore, 25 to 50% less salt would be suitable for cheese crackers if the particle size of regular salt was reduced 3 log to form nano spray-dried salt. A 3-log reduction in sodium chloride particle size from regular salt to nano spray-dried salt increased saltiness, but a 1-log reduction in salt size from Microsized salt to nano spray-dried salt did not increase saltiness of surface-salted cheese crackers. The use of salt with reduced particle size by nano spray drying is recommended for use in surface-salted cheese crackers to reduce sodium intake. PMID- 26142863 TI - Transcriptome profiles of whole blood in Italian Holstein and Italian Simmental lactating cows diverging for genetic merit for milk protein. AB - The aim of the research was to investigate the variation of gene expression in the blood of lactating cows in relation to the genetic merit for productive traits. For the study, 24 Italian Holstein (IH) cows from a single farm and 24 Italian Simmental (IS) cows from a second farm were selected. Cows were in mid lactation, and farms had similar management and feeding conditions. For each breed, cows were separated into 3 classes of estimated breeding value (EBV) for milk protein yield (EBVp), namely, 8 cows with low EBVp (low group, LG), 8 cows with high EBV (high group, HG), and the 8 cows closest to the median (medium group, MG). Gene expression was measured on blood with a whole-transcriptome bovine microarray, and data of LG and HG were expressed relative to MG. The number of differentially expressed genes between the low and high EBVp groups were 443 for IS and 281 for IH cows. The IS cows had a greater number of genes (398 vs. 241 in IH cows) with opposite expression in the high and low EBV groups, compared with the MG. In IS cows, the largest number of pathways affected were within the KEGG subcategories of "energy metabolism," "lipid metabolism," and "metabolism of cofactors and vitamins." Furthermore, the "glutathione metabolism" pathway was markedly affected, with GSTM1 (from glutathione-S-transferase family), GSS (glutathione synthetase), and G6PD (glucose-6-phosphate dehydrogenase) upregulated in the IS HG but downregulated in the IS LG group. The "intestinal immune network for IgA production" pathway had 2 bovine leukocytes antigen (BoLA-DQ) genes, and the B-cell activating factor of the TNF superfamily (TNFSF13B) upregulated in the IS LG group and downregulated in the IS HG group. The IH cows had the highest number of affected pathways in the "metabolism" and "organismal systems" categories, the latter with 5 out of 10 subcategories relative to the immune system. Within the "T cell receptor signaling pathway," the IH HG cows had upregulation of the CD1d, CD4, and CD3 antigens and downregulation of the NFkB subunit ReLa gene. This study revealed that specific metabolic and immunological pathways are directly related to genetic merit, and could be considered a signature of quantitative selection. Starting from these preliminary observations, the comparison of differentially expressed genes among animals with different EBVp seems a promising approach to unravel molecular response at a blood level associated with productive traits. PMID- 26142864 TI - Alcohol dehydrogenase activity in Lactococcus chungangensis: application in cream cheese to moderate alcohol uptake. AB - Many human gastrointestinal facultative anaerobic and aerobic bacteria possess alcohol dehydrogenase (ADH) activity and are therefore capable of oxidizing ethanol to acetaldehyde. However, the ADH activity of Lactococcus spp., except Lactococcus lactis ssp. lactis, has not been widely determined, though they play an important role as the starter for most cheesemaking technologies. Cheese is a functional food recognized as an aid to digestion. In the current study, the ADH activity of Lactococcus chungangensis CAU 28(T) and 11 reference strains from the genus Lactococcus was determined. Only 5 strains, 3 of dairy origin, L. lactis ssp. lactis KCTC 3769(T), L. lactis ssp. cremoris KCCM 40699(T), and Lactococcus raffinolactis DSM 20443(T), and 2 of nondairy origin, Lactococcus fujiensis NJ317(T) and Lactococcus chungangensis CAU 28(T) KCTC 13185(T), showed ADH activity and possessed the ADH gene. All these strains were capable of making cheese, but the highest level of ADH activity was found in L. chungangensis, with 45.9nmol/min per gram in tryptic soy broth and 65.8nmol/min per gram in cream cheese. The extent that consumption of cheese, following imbibing alcohol, reduced alcohol uptake was observed by following the level of alcohol in the serum of mice. The results show a potential novel benefit of cheese as a dairy functional food. PMID- 26142865 TI - Antimicrobial susceptibilities and random amplified polymorphic DNA-PCR fingerprint characterization of Lactococcus lactis ssp. lactis and Lactococcus garvieae isolated from bovine intramammary infections. AB - In total, 181 streptococci-like bacteria isolated from intramammary infections (IMI) were submitted by a veterinary clinic to Quality Milk Production Services (QMPS, Cornell University, Ithaca, NY). The isolates were characterized by sequence analysis, and 46 Lactococcus lactis ssp. lactis and 47 Lactococcus garvieae were tested for susceptibility to 17 antibiotics. No resistant strains were found for beta-lactam antibiotics widely used in clinical practice (penicillin, ampicillin, and amoxicillin), and all minimum inhibitory concentrations (MIC) were far from the resistance breakpoints. Eight strains had MIC intermediate to cefazolin. The random amplification of polymorphic DNA (RAPD) PCR fingerprint patterns showed a slightly higher heterogeneity for Lc. lactis ssp. lactis isolates than for Lc. garvieae isolates. PMID- 26142866 TI - Effect of essential oils of Syzygium aromaticum and Cinnamomum zeylanicum and their major components on biofilm production in Staphylococcus aureus strains isolated from milk of cows with mastitis. AB - Bovine mastitis is an inflammation of the mammary glands of cows and causes significant economic losses in dairy cattle. Staphylococcus aureus is one of the microorganisms most commonly isolated. Novel agents are required in agricultural industries to prevent the development of mastitis. The production of biofilm by Staph. aureus facilitates the adhesion of bacteria to solid surfaces and contributes to the transmission and maintenance of these bacteria. The effect of the essential oils of Syzygium aromaticum (clove; EOSA) and Cinnamomum zeylanicum (cinnamon; EOCZ) and their major components, eugenol and cinnamaldehyde, on Staph. aureus biofilm formation on different surfaces was investigated. The results showed a significant inhibition of biofilm production by EOSA on polystyrene and stainless steel surfaces (69.4 and 63.6%, respectively). However, its major component, eugenol, was less effective on polystyrene and stainless steel (52.8 and 19.6%, respectively). Both EOCZ and its major component, cinnamaldehyde, significantly reduced biofilm formation on polystyrene (74.7 and 69.6%, respectively) and on stainless steel surfaces (45.3 and 44.9%, respectively). These findings suggest that EOSA, EOCZ, and cinnamaldehyde may be considered for applications such as sanitization in the food industry. PMID- 26142867 TI - Personality and production: nervous cows produce less milk. AB - The objective of this study was to investigate relationships between animal personality (i.e., consistency in behavioral responses, also called temperament) and milk production in dairy cows. There has recently been a growing research interest in animal personality, which in production animals can have an important impact on welfare and production potential. Despite this, the relationship between personality and milk production in dairy cows remains unclear. Here we investigate links between behavioral responses during milking and in personality tests (responses to novel object and social isolation) with milk production in 2 breeds of dairy cattle, Swedish Red and White and Holstein. The milk production parameters investigated were energy-corrected milk (in kg) for the cows' first lactation and energy-corrected milk for their current lactation. Overall, cows that stepped more during milking or spent more time facing the herd during social isolation produced less milk in their first lactation. Cows that vocalized more during isolation had a lower current milk production. Variation in other behavioral responses showed limited relationships with milk production. Taken together, our results support a relationship between behavioral responses and milk production, where cows showing signs of nervousness produce less milk. However, observed relationships are dependent on the milk measure used, behavior, and breed investigated, supporting that the relationship between behavior and production traits is not straightforward. PMID- 26142868 TI - The composition and functional properties of whey protein concentrates produced from buttermilk are comparable with those of whey protein concentrates produced from skimmed milk. AB - The demand for whey protein is increasing in the food industry. Traditionally, whey protein concentrates (WPC) and isolates are produced from cheese whey. At present, microfiltration (MF) enables the utilization of whey from skim milk (SM) through milk protein fractionation. This study demonstrates that buttermilk (BM) can be a potential source for the production of a WPC with a comparable composition and functional properties to a WPC obtained by MF of SM. Through the production of WPC powder and a casein- and phospholipid (PL)-rich fraction by the MF of BM, sweet BM may be used in a more optimal and economical way. Sweet cream BM from industrial churning was skimmed before MF with 0.2-um ceramic membranes at 55 to 58 degrees C. The fractionations of BM and SM were performed under the same conditions using the same process, and the whey protein fractions from BM and SM were concentrated by ultrafiltration and diafiltration. The ultrafiltration and diafiltration was performed at 50 degrees C using pasteurized tap water and a membrane with a 20-kDa cut-off to retain as little lactose as possible in the final WPC powders. The ultrafiltrates were subsequently spray dried, and their functional properties and chemical compositions were compared. The amounts of whey protein and PL in the WPC powder from BM (BMWPC) were comparable to the amounts found in the WPC from SM (SMWPC); however, the composition of the PL classes differed. The BMWPC contained less total protein, casein, and lactose compared with SMWPC, as well as higher contents of fat and citric acid. No difference in protein solubility was observed at pH values of 4.6 and 7.0, and the overrun was the same for BMWPC and SMWPC; however, the BMWPC made less stable foam than SMWPC. PMID- 26142869 TI - The role of recent nanotechnology in enhancing the efficacy of radiation therapy. AB - Radiation therapy is one of the most commonly used non-surgical interventions in tumor treatment and is often combined with other modalities to enhance its efficacy. Despite recent advances in radiation oncology, treatment responses, however, vary considerably between individual patients. A variety of approaches have been developed to enhance radiation response or to counteract resistance to ionizing radiation. Among them, a relatively novel class of radiation sensitizers comprises nanoparticles (NPs) which are highly efficient and selective systems in the nanometer range. NPs can either encapsulate radiation sensitizing agents, thereby protecting them from degradation, or sensitize cancer cells to ionizing radiation via their physicochemical properties, e.g. high Z number. Moreover, they can be chemically modified for active molecular targeting and the imaging of tumors. In this review we will focus on recent developments in nanotechnology, different classes and modifications of NPs and their radiation sensitizing properties. PMID- 26142870 TI - Combining glass box and black box evaluations in the identification of heart disease risk factors and their temporal relations from clinical records. AB - BACKGROUND: The determination of risk factors and their temporal relations in natural language patient records is a complex task which has been addressed in the i2b2/UTHealth 2014 shared task. In this context, in most systems it was broadly decomposed into two sub-tasks implemented by two components: entity detection, and temporal relation determination. Task-level ("black box") evaluation is relevant for the final clinical application, whereas component level evaluation ("glass box") is important for system development and progress monitoring. Unfortunately, because of the interaction between entity representation and temporal relation representation, glass box and black box evaluation cannot be managed straightforwardly at the same time in the setting of the i2b2/UTHealth 2014 task, making it difficult to assess reliably the relative performance and contribution of the individual components to the overall task. OBJECTIVE: To identify obstacles and propose methods to cope with this difficulty, and illustrate them through experiments on the i2b2/UTHealth 2014 dataset. METHODS: We outline several solutions to this problem and examine their requirements in terms of adequacy for component-level and task-level evaluation and of changes to the task framework. We select the solution which requires the least modifications to the i2b2 evaluation framework and illustrate it with our system. This system identifies risk factor mentions with a CRF system complemented by hand-designed patterns, identifies and normalizes temporal expressions through a tailored version of the Heideltime tool, and determines temporal relations of each risk factor with a One Rule classifier. RESULTS: Giving a fixed value to the temporal attribute in risk factor identification proved to be the simplest way to evaluate the risk factor detection component independently. This evaluation method enabled us to identify the risk factor detection component as most contributing to the false negatives and false positives of the global system. This led us to redirect further effort to this component, focusing on medication detection, with gains of 7 to 20 recall points and of 3 to 6 F-measure points depending on the corpus and evaluation. CONCLUSION: We proposed a method to achieve a clearer glass box evaluation of risk factor detection and temporal relation detection in clinical texts, which can provide an example to help system development in similar tasks. This glass box evaluation was instrumental in refocusing our efforts and obtaining substantial improvements in risk factor detection. PMID- 26142871 TI - Porphyrias: A 2015 update. AB - The hereditary porphyrias comprise a group of eight metabolic disorders of the heme biosynthesis pathway. Each porphyria is caused by abnormal function at a separate enzymatic step resulting in a specific accumulation of heme precursors. Porphyrias are classified as hepatic or erythropoietic, based on the organ system in which heme precursors (delta-aminolevulinic acid [ALA], porphobilinogen and porphyrins) are overproduced. Clinically, porphyrias are characterized by acute neurovisceral symptoms, skin lesions or both. However, most if not all the porphyrias impair hepatic or gastrointestinal function. Acute hepatic porphyrias present with severe abdominal pain, nausea, constipation, confusion and seizure, which may be life threatening, and patients are at risk of hepatocellular carcinoma without cirrhosis. Porphyria Cutanea presents with skin fragility and blisters, and patients are at risk of hepatocellular carcinoma with liver iron overload. Erythropoietic protoporphyria and X-linked protoporphyria present with acute painful photosensitivity, and patients are at risk of acute liver failure. Altogether, porphyrias are still underdiagnosed, but once they are suspected, early diagnosis based on measurement of biochemical metabolites that accumulate in the blood, urine, or feces is essential so specific treatment can be started as soon as possible and long-term liver complications are prevented. Screening families to identify presymptomatic carriers is also crucial to prevent overt disease and chronic hepatic complications. PMID- 26142872 TI - Prevalence and relationship between gastrointestinal symptoms among individuals of different body mass index: A population-based study. AB - BACKGROUND: Obesity has been identified as a potential risk factor for gastrointestinal (GI) symptoms, although the data from community samples remain sparse. We assess the associations between GI symptoms and obesity in a population-based sample of Australian adults. METHOD: The prevalence of 26 GI symptoms was determined by a validated postal questionnaire which was sent to 5000 randomly selected residents. The response rate was 60%. GI symptoms were classified into six broader symptom groups based on the Rome II Criteria - abdominal pain, esophageal symptoms, dysmotility symptoms, diarrhea, vomiting, and constipation. Obesity was defined according to body mass index using self reported height and weight. RESULTS: The prevalence of obesity (BMI>=30kg/m(2)) was 25.1%; 36.1% were overweight. There were significant and positive univariate associations between obesity and abdominal pain (OR=1.75; 95% CI: 1.39-2.21), esophageal symptoms (OR=1.74; 95% CI: 1.36-2.22), dysmotility symptoms (OR=1.43; 95% CI: 1.16-1.77) and diarrhea (OR=2.01; 95% CI: 1.65-2.45). The adjustment for socioeconomic characteristics and eating behaviors had minimal effect on the associations for abdominal pain (OR=1.34; 95% CI: 1.01-1.79), esophageal symptoms (OR=1.35; 95% CI: 1.03-1.78), and diarrhea (OR=1.86; 95% CI: 1.49-2.31); however, the association between obesity and dysmotility symptoms became non-significant. Obesity was not related to constipation. CONCLUSION: Obesity is an independent risk factor for abdominal pain, esophageal symptoms and diarrhea, but is not associated with dysmotility symptoms or constipation. PMID- 26142873 TI - FiberWire tension band for patellar fractures. AB - BACKGROUND: Symptomatic hardware represents the most frequent complication reported following surgical treatment of patellar fracture. For this reason, some authors suggested using nonabsorbable sutures to fix the fracture with various techniques. The aim of this study was to evaluate clinical and radiological results of patients treated following a modified Pyriford technique using a FiberWire suture (Arthrex, Naples, FL, USA). MATERIALS AND METHODS: We retrospectively evaluated a case series of seventeen patients with displaced patellar fractures treated by open reduction and internal fixation with a modified tension band using FiberWire sutures. Clinical and radiological outcome were evaluated. Union time, complications, and reoperation rate were observed and recorded. RESULTS: All fractures healed (time to union 9.2 +/- 2 weeks), and no fixation failure was observed. Slight losses of reduction (<4 mm) were noted in two patients at 4 weeks postoperatively. The average Lysholm and Bostman scores at the final follow-up were 91 +/- 5.7 (range 83-100) and 28.3 +/- 1.6 (range 26 30), respectively. CONCLUSION: Modified tension band using FiberWire sutures showed satisfactory clinical results, with a low incidence of complications and reoperations. FiberWire tension bands could be used in place of metal-wire tension bands to treat patellar fracture, reducing the rate of symptomatic hardware. LEVEL OF EVIDENCE: 4. PMID- 26142875 TI - Biotransformation of pink water TNT on the surface of a low-cost adsorbent pine bark. AB - This two-week anaerobic batch study evaluated 2,4,6-trinitrotoluene (TNT) removal efficiency from industrial pink water by (1) adsorption on low-cost adsorbent pine bark, and (2) adsorption coupled with TNT biotransformation by specialised microbial communities. Samples of the supernatant and acetonitrile extracts of pine bark were analysed by HPLC, while the composition of the bacterial community of the experimental batches, inocula and pine bark were profiled by high throughput sequencing the V6 region of the bacterial 16S rRNA gene. Integrated adsorption and biotransformation proved to be the most efficient method for TNT removal from pink water. The type of applied inoculum had a profound effect on TNT removal efficiencies and microbial community structures, which were dominated by phylotypes belonging to the Enterobacteriaceae family. The analysis of acetonitrile extracts of pine bark supported the hypothesis that the microbial community indigenous to pine bark has the ability to degrade TNT. PMID- 26142874 TI - Dual inhibition of mTOR pathway and VEGF signalling in neuroendocrine neoplasms: from bench to bedside. AB - After years of limited progress in the treatment of neuroendocrine neoplasms (NENs), an increasing number of therapeutic targets have recently emerged as potential tools to improve disease outcome. The mammalian target of rapamycin (mTOR) pathway and vascular endothelial growth factor (VEGF) signalling are implicated in the regulation of cell growth, proliferation, neo-angiogenesis and tumour cell spread. Their combined blockade, in a simultaneous or sequential strategy, represents an intriguing biological rationale to overcome the onset of resistance mechanisms. However, is becoming increasingly imperative to find the optimal sequential strategy according to the best toxicity profile, and also to identify predictive biomarkers. We will provide an overview of the pre-clinical and clinical data relating to mTOR pathway/VEGF signalling as a potential targets of treatment in NENs. PMID- 26142876 TI - Resting-state EEG coupling analysis of amnestic mild cognitive impairment with type 2 diabetes mellitus by using permutation conditional mutual information. AB - OBJECTIVE: This study was meant to explore whether the coupling strength and direction of resting-state electroencephalogram (rsEEG) could be used as an indicator to distinguish the patients of type 2 diabetes mellitus (T2DM) with or without amnestic mild cognitive impairment (aMCI). METHODS: Permutation conditional mutual information (PCMI) was used to calculate the coupling strength and direction of rsEEG signals between different brain areas of 19 aMCI and 20 normal control (NC) with T2DM on 7 frequency bands: Delta, Theta, Alpha1, Alpha2, Beta1, Beta2 and Gamma. The difference in coupling strength or direction of rsEEG between two groups was calculated. The correlation between coupling strength or direction of rsEEG and score of different neuropsychology scales were also calculated. RESULTS: We have demonstrated that PCMI can calculate effectively the coupling strength and directionality of EEG signals between different brain regions. The significant difference in coupling strength and directionality of EEG signals was found between the patients of aMCI and NC with T2DM on different brain regions. There also existed significant correlation between sex or age and coupling strength or coupling directionality of EEG signals between a few different brain regions from all subjects. CONCLUSIONS: The coupling strength or directionality of EEG signals calculated by PCMI are significantly different between aMCI and NC with T2DM. SIGNIFICANCE: These results showed that the coupling strength or directionality of EEG signals calculated by PCMI might be used as a biomarker in distinguishing the aMCI from NC with T2DM. PMID- 26142877 TI - Atypical cortical drive during activation of the paretic and nonparetic tibialis anterior is related to gait deficits in chronic stroke. AB - OBJECTIVE: The role of cortical drive in stroke recovery for the lower extremity remains ambiguous. The purpose of this study was to investigate the relationship between cortical drive and gait speed in a group of stroke survivors. METHODS: Eighteen individuals with stroke were dichotomized into fast or slow walking groups. Transcranial magnetic stimulation (TMS) was used to collect motor evoked potentials (MEPs) from the tibialis anterior of each lower extremity during rest, paretic muscle contractions, and nonparetic muscle contractions. An asymmetry index (AI) was calculated using motor thresholds and compared between groups. The average MEP of the paretic leg during TMS at maximal intensity (MEP100) for each condition was compared within and between groups. RESULTS: A significant positive correlation was found between AI and walking speed. Slow-walkers had greater MEP100s during the nonparetic contraction than during the paretic contraction or rest conditions. In contrast, fast-walkers had greatest MEP100s during the paretic contraction. CONCLUSIONS: Alterations in the balance of corticomotor excitability occur in the lower extremity of individuals with poor motor recovery post-stroke. This atypical cortical drive is dependent on activation of the unaffected hemisphere and contraction of the nonparetic leg. SIGNIFICANCE: Understanding mechanisms underlying motor function can help to identify specific patient deficits that impair function. PMID- 26142878 TI - mtDNA analysis of 174 Eurasian populations using a new iterative rank correlation method. AB - In this study, we analyse 27-dimensional mtDNA haplogroup distributions of 174 Eurasian, North-African and American populations, including numerous ancient data as well. The main contribution of this work was the description of the haplogroup distribution of recent and ancient populations as compounds of certain hypothetic ancient core populations immediately or indirectly determining the migration processes in Eurasia for a long time. To identify these core populations, we developed a new iterative algorithm determining clusters of the 27 mtDNA haplogroups studied having strong rank correlation among each other within a definite subset of the populations. Based on this study, the current Eurasian populations can be considered as compounds of three early core populations regarding to maternal lineages. We wanted to show that a simultaneous analysis of ancient and recent data using a new iterative rank correlation algorithm and the weighted SOC learning technique may reveal the most important and deterministic migration processes in the past. This technique allowed us to determine geographically, historically and linguistically well-interpretable clusters of our dataset having a very specific, hardly classifiable structure. The method was validated using a 2-dimensional stepping stone model. PMID- 26142879 TI - Complete Endovascular Treatment of Saccular Aneurysm of the Aortic Arch by Coiling and ch-EVAR. AB - Saccular aneurysm of the aortic arch is a condition with a high associated mortality. Open surgery is often complicated with poor outcome and high postoperative morbidity and mortality. In this case report, we describe an alternative stepwise endovascular repair: coiling of the aneurysm followed by covering of the ostium of the saccular aneurysm by chimney endovascular aortic repair. In our opinion, this technique could be an alternative for a fully customized branched or fenestrated endoprosthesis to treat these kind of aneurysms. PMID- 26142880 TI - Endovascular Treatment of Infected Brachial Pseudoaneurysm in an Intravenous Drug Abuser: A Case Report. AB - We report the case of a 36-year-old male, admitted in the emergency room with a nonruptured brachial pseudoaneurysm after buprenorphine injection, with no signs of distal acute ischemia. After endovascular treatment with a nitinol covered stent associated with adapted antibiotherapy and 35 days of hospitalizations, the patient was discharged with good short results but stent need to be removed at 6 months for thrombosis and partial exposure through the wound. PMID- 26142881 TI - Pneumomediastinum and cervical emphysema as a debut of colorectal anastomotic leakage. PMID- 26142882 TI - Appendicular foreign body. PMID- 26142883 TI - Arterial vascularization of the flexor digitorum superficialis synovial flap. An anatomical study. AB - Among the various techniques proposed to protect the median nerve from scarring and to provide it with a vascular supply, the synovial flap represents a simple and effective method. The flap is taken from the flexor tendons sheath and results in a thin and richly vascularized tissue that will act as a barrier to scarring and provide neovascularization to improve nerve regeneration and gliding. The aim of this study was to evaluate the arterial vascularization of this flap to assess its reliability. An anatomic study was carried out on 24 fresh upper limbs infused with colored and radiopaque solutions before or after flap elevation. Anatomical findings showed the synovial flap to be supplied by a consistent vascular pedicle arising from the ulnar artery 2 to 5 centimeters proximal to the pisiform bone and running between the flexor tendons of the ring and little fingers. The synovial flap is known to be a simple and effective method for protecting the median nerve. The present study shows that its consistent vascularization makes it a reliable technique. We believe this procedure is relevant for the treatment of recurring carpal tunnel syndrome. PMID- 26142884 TI - Development of a technique to detect the activated form of the progesterone receptor and correlation with clinical and histopathological characteristics of endometrioid adenocarcinoma of the uterine corpus. AB - OBJECTIVE: Hormonal therapy is generally reserved for patients with endometrial cancers that fail cytotoxic chemotherapy, but there is a lack of sufficiently sensitive diagnostics to identify potential responders. We sought to develop a diagnostic technique to detect activated progesterone receptors (APR) in endometrial cancers using routine immunohistochemistry (IHC) and to correlate the presence of APR with other histopathological features and clinical disease stage. METHODS: Seventy-two tumor block specimens from patients with endometrial cancer were processed with conventional IHC methods for estrogen receptor-alpha (ERalpha), progesterone receptor (PR) and Ki67, a marker of proliferation. Tumor specimens were analyzed for the PR nuclear distribution patterns in individual tumor cells: APR positive (APR(pos)) tumors were prospectively defined as any tumor with >5% countable malignant cells with an aggregated nuclear pattern. Tumor APR status was analyzed against other biomarkers including ERalpha expression, Ki67 and tumor grade. RESULTS: Fifty-six of 72 samples were endometrioid. Twenty-six of 49 PR-positive endometrioid tumors (53%; 95% CI 39 67%) were APR(pos). Percent of ER(pos) cells correlated with % PR(pos) malignant cells (p=0.001, rho=0.44). APR positivity did not correlate with % PR(pos) cells in a given tumor, nor did it correlate with % Ki67 positivity; APR positivity was independent of disease stage and tumor grade (p=NS). CONCLUSIONS: In this study, approximately half of endometrioid tumors were APR(pos). APR is independent of histopathological and other known risk factors. Refining conventional PR detection has the potential to prospectively identify patients with endometrial cancer who may benefit from anti-progestin therapy. PMID- 26142885 TI - Differential impact of local stiffening and narrowing on hemodynamics in repaired aortic coarctation: an FSI study. AB - Even after successful treatment of aortic coarctation, a high risk of cardiovascular morbidity and mortality remains. Uncertainty exists on the factors contributing to this increased risk among which are the presence of (1) a residual narrowing leading to an additional resistance and (2) a less distensible zone disturbing the buffer function of the aorta. As the many interfering factors and adaptive physiological mechanisms present in vivo prohibit the study of the isolated impact of these individual factors, a numerical fluid-structure interaction model is developed to predict central hemodynamics in coarctation treatment. The overall impact of a stiffening on the hemodynamics is limited, with a small increase in systolic pressure (up to 8 mmHg) proximal to the stiffening which is amplified with increasing stiffening and length. A residual narrowing, on the other hand, affects the hemodynamics significantly. For a short segment (10 mm), the combination of a stiffening and narrowing (coarctation index 0.5) causes an increase in systolic pressure of 58 mmHg, with 31 mmHg due to narrowing and an additional 27 mmHg due to stiffening. For a longer segment (25 mm), an increase in systolic pressure of 50 mmHg is found, of which only 9 mmHg is due to stiffening. PMID- 26142886 TI - Targeting strategies on miRNA-21 and PDCD4 for glioblastoma. AB - MicroRNAs (miRNAs) are often deregulated in glioblastoma multiforme (GBM). Downregulation of microRNA-21 (miR-21), especially in GBM, is responsible for increased apoptosis, decreased cell proliferation and invasion, increased G0/G1 cell cycle arrest, and reduced chemotherapeutic resistance to doxorubicin. Furthermore, it is a critical regulator of multiple downstream genes and signaling pathways involved in gliomagenesis. Programmed cell death 4 (PDCD4) is critical in mediating apoptosis in GBM, and is downregulated by miR-21, which may mediate the resistance of glioblastoma cells against chemotherapy or radiation via its target genes PDCD4. Evidence is mounting that how alterations of these miRNAs transcription factors provide initiation, maintenance, or progression of tumors. This review will focus on the roles of miRNAs family members (particularly miR-21 and its target gene PDCD4) in tumors like glioblastoma and new targeting strategies, as examples some new targeting therapeutic methods and molecular mechanisms of signal pathways in glioblastoma therapeutics, to give the reader the current trends of approach to target regulation of these miRNA and genes for future glioma therapies. PMID- 26142887 TI - Can Perceptions of Environmental and Climate Change in Island Communities Assist in Adaptation Planning Locally? AB - Local perceptions of environmental and climate change, as well as associated adaptations made by local populations, are fundamental for designing comprehensive and inclusive mitigation and adaptation plans both locally and nationally. In this paper, we analyze people's perceptions of environmental and climate-related transformations in communities across the Western Solomon Islands through ethnographic and geospatial methods. Specifically, we documented people's observed changes over the past decades across various environmental domains, and for each change, we asked respondents to identify the causes, timing, and people's adaptive responses. We also incorporated this information into a geographical information system database to produce broad-scale base maps of local perceptions of environmental change. Results suggest that people detected changes that tended to be acute (e.g., water clarity, logging intensity, and agricultural diseases). We inferred from these results that most local observations of and adaptations to change were related to parts of environment/ecosystem that are most directly or indirectly related to harvesting strategies. On the other hand, people were less aware of slower insidious/chronic changes identified by scientific studies. For the Solomon Islands and similar contexts in the insular tropics, a broader anticipatory adaptation planning strategy to climate change should include a mix of local scientific studies and local observations of ongoing ecological changes. PMID- 26142888 TI - Denaturation and Oxidative Stability of Hemp Seed (Cannabis sativa L.) Protein Isolate as Affected by Heat Treatment. AB - The present study investigated the impact of heat treatments on the denaturation and oxidative stability of hemp seed protein during simulated gastrointestinal digestion (GID). Heat-denatured hemp protein isolate (HPI) solutions were prepared by heating HPI (2 mg/ml, pH 6.8) to 40, 60, 80 and 100 degrees C for 10 min. Heat-induced denaturation of the protein isolates was monitored by polyacrylamide gel electrophoresis. Heating HPI at temperatures above 80 degrees C significantly reduced solubility and led to the formation of large protein aggregates. The isolates were then subjected to in vitro GID and the oxidative stability of the generated peptides was investigated. Heating did not significantly affect the formation of oxidation products during GID. The results suggest that heat treatments should ideally remain below 80 degrees C if heat stability and solubility of HPI are to be preserved. PMID- 26142889 TI - Protective effect of a calcium channel blocker "diltiazem" on aluminum chloride induced dementia in mice. AB - Many studies report that heavy metals such as aluminum are involved in amyloid beta aggregation and neurotoxicity. Further, high concentration of aluminum in the brain deregulates calcium signaling which contributes to synaptic dysfunction and halts neuronal communication which ultimately leads to the development of Alzheimer's disease. Recently, diltiazem, a calcium channel blocker clinically used in angina, is reported to decrease amyloid beta production by inhibiting calcium influx, decreasing inflammation and oxidative stress. However, the probable role of this drug in aluminum chloride (AlCl3)-induced experimental dementia is yet to be explored. Therefore, the present study is designed to investigate the effect of AlCl3-induced dementia in mice. Morris water maze test and elevated plus maze were utilized to evaluate learning and memory. Various biochemical estimations including brain acetylcholinesterase activity (AChE), brain total protein, thiobarbituric acid-reactive species (TBARS) level, reduced glutathione (GSH) level, nitrate/nitrite, and superoxide dismutase (SOD) were measured. AlCl3 significantly impaired learning and memory and increased brain AChE, brain total protein, TBARS, and nitrate/nitrite and decreased brain GSH or SOD. On the other hand, treatment with diltiazem significantly reversed AlCl3 induced behavioral and biochemical deficits. The present study indicates the beneficial role of diltiazem in AlCl3-induced dementia. PMID- 26142890 TI - Early Glycemic Response Predicts Achievement of Subsequent Treatment Targets in the Treatment of Type 2 Diabetes: A Post hoc Analysis. AB - INTRODUCTION: American Diabetes Association consensus guidelines emphasize individualized treatment in the management of type 2 diabetes mellitus (T2DM). Early glycemic response is a clinical marker that may predict longer term efficacy for individual patients and provide a clinical tool to enhance personalized treatment. This analysis evaluated whether glycemic response measured at week 12 ("early") could serve as a reliable predictor of glycemic control at weeks 24 and 52 of therapy in patients with T2DM. METHODS: We used data from 3 randomized, controlled clinical trials that evaluated patients with T2DM treated with 3 commonly prescribed glucose-lowering medications: metformin (n = 597), sulfonylurea (n = 626), and insulin glargine (n = 1046). The gradient boosting method was used to identify predictors of subsequent response; predictive accuracy was represented by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Treatment success at weeks 24 and 52 was assessed for each patient and defined as achieving a glycated hemoglobin (HbA1c) level of <7.0% or a reduction from baseline of >=1.0%. RESULTS: The predictive parameters (sensitivity, specificity, PPV, and NPV) for improvements in HbA1c at week 24 for metformin were 0.83, 0.81, 0.44, and 0.96; for sulfonylurea, 0.79, 0.94, 0.71, and 0.96; and for insulin glargine, 0.67, 0.89, 0.65, and 0.90. The predictive parameters for improvements in HbA1c at week 52 for metformin were 0.73, 0.84, 0.56, and 0.92 and for sulfonylurea, 0.45, 0.94, 0.74, and 0.82. CONCLUSION: High predictive values identified in this analysis support "early" response as an appropriate tool for predicting treatment success at weeks 24 and 52. The high NPV (lack of early glycemic response) appears to be an effective indicator of the likely need for change in (or intensification of) therapy. These data support the current guideline recommendations that clinicians evaluate therapeutic responses to pharmacologic interventions with metformin, sulfonylureas, or insulin glargine as early as week 12. PMID- 26142891 TI - The Evolving Role of Short-Term Professional Continuous Glucose Monitoring on Glycemic Control and Hypoglycemia Among Saudi Patients with Type 1 Diabetes: A Prospective Study. AB - INTRODUCTION: The aim of this study was to find out the evolving role of professional continuous glucose monitoring (PCGM) on hemoglobin A1c (HbA1c) and the frequency of hypoglycemia. METHODS: This was a 3-month, prospective study conducted among patients (aged 15-24 years) with type 1 diabetes mellitus who attended a diabetes clinic [Diabetes Treatment Center, Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia] due to recurrent unexplained hypoglycemia unawareness episodes between July 2014 and December 2014. The respondents were purposively and conveniently selected and they were asked to wear the PCGM device (iPro((r))2; Medtronic MiniMed, Inc., Northridge, CA, USA) for 5 days. The PCGM results were collected by the diabetic educator and reviewed by the treating physician on the same day as removal of the device. Clinical and demographic data were also collected. RESULTS: Overall, 56 patients were included in the study. The mean (+/-SD) age of the study cohort was 18.1 +/- 1.82 years and 27 (48.2%) patients were male. Compared with baseline, non-significant but positive differences were observed in HbA1c levels in both male and female patients and in those who were older (aged 20-24 years). Similar results were observed in the frequency of hypoglycemia and a significant change was observed for female patients (P < 0.05). Compared with baseline, a significant positive difference was observed in patients' overall frequency of hypoglycemia by the end of the study (P < 0.001). CONCLUSIONS: Professional continuous glucose monitoring is a valuable tool for detecting episodes of hypoglycemia and may help to decrease HbA1c levels and reduce the frequency of hypoglycemia. PMID- 26142892 TI - Restoring vaginal microbiota: biological control of bacterial vaginosis. A prospective case-control study using Lactobacillus rhamnosus BMX 54 as adjuvant treatment against bacterial vaginosis. AB - PURPOSE: Bacterial vaginosis (BV) is the most prevalent lower genital tract infection in reproductive-age women worldwide. BV is an ecological disorder of the vaginal microbiota characterized microbiologically by replacement of the lactobacilli, predominant vaginal microbiota. It is characterized by a high rate of relapse in sexual active women, and these patients show three or more relapses each year. A healthy vagina is characterized by hydrogen peroxide and acid producing lactobacilli, which are crucial to maintain the physiological vaginal ecosystem and their depletion speeds up bacterial overgrowth with pH elevation, salidase and amine production, leading to the observed signs and symptoms of BV. The aim of this study is to evaluate the efficacy of long-term vaginal lactobacilli's implementation in restoring and maintaining vaginal microflora and pH and to collect data about prophylactic approach based on probiotics supplementation with lactobacilli. METHODS: This is a prospective case-control study, performed between January 2013 and September 2014 at Department of Gynecological Obstetrics and Urologic Sciences of "Sapienza" University of Rome. 250 non-pregnant sexually active women with diagnoses of BV were collected. Patients selected were divided in Group A (125 patients assigned to standard treatment for BV-metronidazole 500 mg orally twice a day for 7 days) and Group B (125 women undergoing the same standard antibiotic regimen followed by vaginal tablets containing Lactobacillus rhamnosus BMX 54). Patients were evaluated after 2, 6, and 9 months (T0, T2, T6, and T9) in term of recurrences rates of BV, vaginal symptoms, re-establishment of healthy vaginal flora, vaginal pH, and treatment tolerability. RESULTS: Vaginal flora was significantly replaced in Group B patients after 2 months comparing with Group A (p = 0.014). These data were confirmed at 6 and 9 months follow-up: patients that underwent prophylactic therapy with NORMOGIN((r)) experienced significantly low rate of recurrences comparing with patients treated with antibiotics only (p < 0.001). During follow up patients continuing supplementation had significant pH decrease respect to other patients (p < 0.001 at 9 months follow-up visit). CONCLUSIONS: Probiotic supplementation with vaginal Lactobacillus rhamnosus BMX54 seems to be useful in hindering bacteria growth especially after antibiotic therapy; therefore this intervention may be considered a new prophylactic treatment for preventing recurrence of BV, in particular in high-risk patients. PMID- 26142893 TI - Charles Richard de Beauregard and the treatment of blennorrhagic urethral stenosis in Madrid in the 18th century: Advertising, secrecy and deception. AB - OBJECTIVES: Describe the introduction of the treatment for blennorrhagic urethral stenosis in the city of Madrid in the 18th century by the French surgeon Charles de Beauregard, the formulations employed in the preparation of his personal "bougies", the advertising in the press, their marketing and distribution. MATERIAL AND METHODS: Nonsystematic review of the Madrid newspaper Gaceta de Madrid y Diario curioso, erudito, economico y comercial (Madrid Gazette, curious, erudite, financial and commercial) between 1759 and 1790. Review of the medical literature of the 18th century preserved in the Fondo Antiguo of the Biblioteca Historica of Universidad Complutense de Madrid (Historical Resource of the Historical Library of the Complutense University of Madrid). A Google search of "Charles Richard de Beauregard". RESULTS: Charles de Beauregard focused his professional work mainly on the treatment of the urethral sequela of blennorrhagia, phimosis and paraphimosis. He introduced to 18th century Spanish society (with purported originality and clear commercial interests) therapeutic methods based on lead acetate that had already been developed in France by Thomas Goulard. CONCLUSIONS: The urethral sequela of diseases such as blennorrhagic urethritis, stenotic phimosis and paraphimosis were highly prevalent in 18th century Madrid and required complex solutions for the practice of urology of that era. Charles de Beauregard introduced innovative but not original treatments that were invasive but not bloody and that provided him with fame and social prestige. He advertised his professional activity and marketed his therapeutic products through advertisements submitted to the daily press (Madrid Gazette, Gaceta de Madrid). PMID- 26142894 TI - Metastatic malignant melanoma of the urinary bladder. PMID- 26142895 TI - The results of implementing a fast-track protocol in radical cystectomy in a tertiary hospital. AB - BACKGROUND: Radical cystectomy (RC) is the urological procedure associated with the highest rates of morbidity, mortality and hospital stay. The implementation of fast-track programs seeks to speed postsurgical recovery. Its application to radical cystectomy has yielded positive results. OBJECTIVES: To assess the results of the fast-track protocol in RC at our hospital, in terms of morbidity, mortality and hospital stay, comparing these results with those of patients who underwent RC following the classic protocol. To thereby ascertain whether the implementation of the fast-track protocol represents a reduced number and severity of complications and shorter hospital stays. MATERIAL AND METHODS: Ambispective cohort study of patients who underwent RC between January 2010 and October 2012 by either protocol (classic and fast-track). We analyzed the patient characteristics, intraoperative variables, postoperative complications (according to the Clavien classification), hospital stay and recovery stay. RESULTS: Ninety nine patients were included, 51 following the classic protocol and 48 following the fast-track protocol. The groups were homogeneous. The hospital stay and recovery stay were longer in the classic group than in the fast-track group (29 and 2 days, respectively, vs. 17 and 1 day). There was less intraoperative bleeding in the fast track group (600mL) than in the traditional group (1,000mL). Of the 99 patients, 31 (60.8%) of the classic group presented a postoperative complication, while the fast-track group had 14 (29.2%), most of which were minor (Clavien degrees 1 and 2). In the multivariate analysis, the type of protocol and the number of comorbidities were significant. CONCLUSIONS: The implementation of the fast-track protocol in RC was associated with a significant reduction in intraoperative and postoperative complications and hospital stay. PMID- 26142896 TI - Pathophysiology and risk factors for osteonecrosis. AB - Osteonecrosis, also known as avascular necrosis or AVN, is characterized by a stereotypical pattern of cell death and a complex repair process of bone resorption and formation. It is not the necrosis itself but rather the resorptive component of the repair process that results in loss of structural integrity and subchondral fracture. Most likely, a common pathophysiological pathway exists involving compromised subchondral microcirculation. Decreased femoral head blood flow can occur through three mechanisms: vascular interruption by fractures or dislocation, intravascular occlusion from thrombi or embolic fat, or intraosseous extravascular compression from lipocyte hypertrophy or Gaucher cells. In this review, we emphasize etiologic relationships derived mostly from longitudinal cohort studies or meta-analyses whose causal relationships to osteonecrosis can be estimated with confidence. Understanding risk factors and pathophysiology has therapeutic implications since several treatment regimens are available to optimize femoral head circulation, interrupt bone resorption, and preserve the subchondral bone. PMID- 26142898 TI - Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. AB - BACKGROUND: It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial. OBJECTIVES: To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 January 2015), searched reference lists of retrieved studies and contacted authors for further data. SELECTION CRITERIA: Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth. DATA COLLECTION AND ANALYSIS: We assessed trial quality and extracted data independently. MAIN RESULTS: We included 10 trials (a total of 4733 women and 5700 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, number needed to treat to benefit (NNTB) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNTB 30, 95% CI 19 to 79).Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) -75.79 g, 95% CI -117.63 to -33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.At early childhood follow-up, no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments. In women, for the two primary outcomes, there was no increase in infectious morbidity of chorioamnionitis or puerperal sepsis, and the likelihood of a caesarean birth was unchanged. AUTHORS' CONCLUSIONS: The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm. PMID- 26142897 TI - Mobility and cognition are associated with wellbeing and health related quality of life among older adults: a cross-sectional analysis of the Vancouver Falls Prevention Cohort. AB - BACKGROUND: Ascertaining individuals' quality of life and wellbeing is essential in public health and clinical research. The impact of these two pressing geriatric syndromes--impaired mobility and cognitive function--on wellbeing and quality of life is not well examined. Hence, our objective was to identify key clinically relevant outcome measures of mobility and cognitive function that explain variation in wellbeing and health related quality of life (HRQoL) among community dwelling older adults. METHODS: We conducted a cross-sectional analysis of 229 participants presenting to the Vancouver Falls Prevention Clinic from June 2010 through October 2013. The linear regression models included two dependent variables: the ICECAP-O assessing wellbeing and the EQ-5D-3L assessing HRQoL. Key independent variables included the Short Performance Physical Battery (SPPB) and the Montreal Cognitive Assessment (MoCA). Covariates included Functional Comorbidity Index (FCI), sex and age. In the two multiple linear regression models, age was statistically controlled. Other covariates (i.e., sex and FCI) were included based on statistical significance (i.e., p < 0.05). RESULTS: The SPPB was significantly associated with HRQoL and with wellbeing after adjusting for known covariates (p < 0.05, Unstandardized beta (Standard Error) 0.023 (0.006) for HRQoL and 0.016 (0.003) for wellbeing). The MoCA was significantly associated with wellbeing after adjusting for known covariates (p = 0.006), Unstandardized beta (Standard Error) 0.005 (0.002) but not with health related quality of life (p > 0.05). CONCLUSION: We found that a measure of mobility and balance was associated with HRQoL and wellbeing. However, cognitive function was associated with wellbeing only. This study highlights the potential importance of considering wellbeing as an outcome measure if interventions are intended to have a broader impact than health alone. PMID- 26142899 TI - Effectiveness of a systematic approach to promote intersectoral collaboration in comprehensive school health promotion-a multiple-case study using quantitative and qualitative data. AB - BACKGROUND: We report on the longitudinal quantitative and qualitative data resulting from a two-year trajectory (2008-2011) based on the DIagnosis of Sustainable Collaboration (DISC) model. This trajectory aimed to support regional coordinators of comprehensive school health promotion (CSHP) in systematically developing change management and project management to establish intersectoral collaboration. METHODS: Multilevel analyses of quantitative data on the determinants of collaborations according to the DISC model were done, with 90 respondents (response 57 %) at pretest and 69 respondents (52 %) at posttest. Nvivo analyses of the qualitative data collected during the trajectory included minutes of monthly/bimonthly personal/telephone interviews (N = 65) with regional coordinators, and documents they produced about their activities. RESULTS: Quantitative data showed major improvements in change management and project management. There were also improvements in consensus development, commitment formation, formalization of the CSHP, and alignment of policies, although organizational problems within the collaboration increased. Content analyses of qualitative data identified five main management styles, including (1) facilitating active involvement of relevant parties; (2) informing collaborating parties; (3) controlling and (4) supporting their task accomplishment; and (5) coordinating the collaborative processes. CONCLUSIONS: We have contributed to the fundamental understanding of the development of intersectoral collaboration by combining qualitative and quantitative data. Our results support a systematic approach to intersectoral collaboration using the DISC model. They also suggest five main management styles to improve intersectoral collaboration in the initial stage. The outcomes are useful for health professionals involved in similar ventures. PMID- 26142900 TI - Cloning and Genomic Organization of a Rhamnogalacturonase Gene from Locally Isolated Strain of Aspergillus niger. AB - The rhg gene encoding a rhamnogalacturonase was isolated from the novel strain A1 of Aspergillus niger. It consists of an ORF of 1.505 kb encoding a putative protein of 446 amino acids with a predicted molecular mass of 47 kDa, belonging to the family 28 of glycosyl hydrolases. The nature and position of amino acids comprising the active site as well as the three-dimensional structure were well conserved between the A. niger CTM10548 and fungal rhamnogalacturonases. The coding region of the rhg gene is interrupted by three short introns of 56 (introns 1 and 3) and 52 (intron 2) bp in length. The comparison of the peptide sequence with A. niger rhg sequences revealed that the A1 rhg should be an endo rhamnogalacturonases, more homologous to rhg A than rhg B A. niger known enzymes. The comparison of rhg nucleotide sequence from A. niger A1 with rhg A from A. niger shows several base changes. Most of these changes (59 %) are located at the third base of codons suggesting maintaining the same enzyme function. We used the rhamnogalacturonase A from Aspergillus aculeatus as a template to build a structural model of rhg A1 that adopted a right-handed parallel beta-helix. PMID- 26142901 TI - Antibacterial and Antifungal Activity of Biopolymers Modified with Ionic Liquid and Laponite. AB - In the present study, the antimicrobial properties of modified biopolymers such as gelatin and agar have been investigated. These biopolymers (agar and gelatin) are modified by dissolving in ionic liquid (IL) [1-ethyl-3-methylimidazolium chloride ([C2mim][Cl]) and 1-octyl-3-methyl imidazolium chloride ([C8mim][Cl])] solutions. It was noticed that agar-ionogel (Ag-IL), gelatin-ionogel (GB-IL), and gelatin organogel (gelatin-glycerol solution along with laponite, nanoclay) nanocomposite (GA-NC) formed are highly stable, optically clear, and transparent without any air bubbles. The antimicrobial activity of these (Ag-IL), (GB-IL), and GA-NC were analyzed for both gram-negative (Escherichia coli, Klebsiella pneumoniae) and gram-positive bacterial strains (Staphylococcus aureus and Staphylococcus pyogenes) and fungus A. niger, C. albicans. Antibacterial and antifungal activity studies were carried out at different dilutions such as 100, 99, and 90 % (v/v). It was found that Ag-IL, GB-IL, and individual IL ([C8mim][Cl]) exhibited superior antimicrobial activities, indicating that longer IL chain enhance the cell membrane permeability of S. aureus, S. pyogenes, and E. coli cells. However, GA-NC nanocomposite and [C2mim][Cl]-based composites does not exhibit any bacterial inhibition activity for all bacterial strains. PMID- 26142902 TI - The Structure and Enzyme Characteristics of a Recombinant Leucine Aminopeptidase rLap1 from Aspergillus sojae and Its Application in Debittering. AB - A leucine aminopeptidase Lap1 was cloned from Aspergillus sojae GIM3.30. The truncated Lap1 without a signal peptide was over-expressed in P. pastoris, and the enzymatic characteristics of recombinant Lap1 (rLap1) were tested. The rLap1 was about 36.7 kDa with an optimal pH 8.0 and optimal temperature 50 degrees C for substrate Leu-p-nitroanilide and it sustained 50 % activity after 1 h incubation at 50 degrees C. The activity of rLap1 was significantly inhibited by EDTA, whereas Co(2+), Mn(2+), and Ca(2+) ions, but not Zn(2+) ions, restored its activity. rLap1 showed the highest activity against Arg-pNA and then Leu-, Lys-, Met-, and Phe-pNA. The 3D structure of rLap1 showed it had a conserved functional charge/dipole complex and a hydrogen bond network of Zn2-D179-S228-Q177-D229-S158 around its active center. An acidic Asp residue was found at the bottom of the substrate binding pocket, which explains its preference for basic N-terminal amino acid substrates such as Arg and Lys. rLap1 improved the degree of hydrolysis of casein and soy protein hydrolysates and also decreased their bitterness, indicating its potential utility in food production. PMID- 26142903 TI - Characterization of Phosphoenolpyruvate Carboxylase from Oceanimonas smirnovii in Escherichia coli. AB - In this study, phosphoenolpyruvate carboxylase (PEPC) derived from Oceanimonas smirnovii (OS) was expressed as a soluble protein in Escherichia coli BL21(DE3). We isolated OS-PEPC (a recombinant PEPC protein) by his-tag purification. The purified protein showed a single band upon analysis with SDS-PAGE, and it had an apparent molecular mass of 98 kDa. Pufied OS-PEPC showed a specific activity value of 21.8 +/- 0.495 U/mg protein. Especially, OS-PEPC showed the enzymatic activity between 40 and 50 degrees C. It maintained enzymatic activity in basic pH conditions (pH value, 9-10). We also measured OS-PEPC PEP and HCO3 (-) saturation kinetics and confirmed the effect of divalent cation on OS-PEPC activity. PMID- 26142904 TI - Assessment of mosquito larval productivity among different land use types for targeted malaria vector control in the western Kenya highlands. AB - BACKGROUND: Mosquito larval source management (LSM) is likely to be more effective when adequate information such as dominant species, seasonal abundance, type of productive habitat, and land use type are available for targeted sites. LSM has been an effective strategy for reducing malaria morbidity in both urban and rural areas in Africa where sufficient proportions of larval habitats can be targeted. In this study, we conducted longitudinal larval source surveillance in the western Kenya highlands, generating data which can be used to establish cost effective targeted intervention tools. METHODS: One hundred and twenty-four (124) positive larval habitats were monitored weekly and sampled for mosquito larvae over the 85-week period from 28 July 2009 to 3 March 2011. Two villages in the western Kenya highlands, Mbale and Iguhu, were included in the study. After preliminary sampling, habitats were classified into four types: hoof prints (n = 21; 17 % of total), swamps (n = 32; 26%), abandoned goldmines (n = 35; 28%) and drainage ditches (n = 36; 29%). Positive habitats occurred in two land use types: farmland (66) and pasture (58). No positive larval habitats occurred in shrub land or forest. RESULTS: A total of 46,846 larvae were sampled, of which 44.1% (20,907) were from abandoned goldmines, 30.9% (14,469) from drainage ditches, 22.4% (10,499) from swamps and 2.1% (971) from hoof prints. In terms of land use types, 57.2% (26,799) of the sampled larvae were from pasture and 42.8% (20,047) were from farmland. Of the specimens identified morphologically, 24,583 (52.5%) were Anopheles gambiae s.l., 11,901 (25.4%) were Culex quinquefasciatus, 5628 (12%) were An. funestus s.l. and 4734 (10.1%) were other anopheline species (An. coustani, An. squamosus, An. ziemanni or An. implexus). Malaria vector dynamics varied seasonally, with An.gambiae s.s. dominating during wet season and An.arabiensis during dry season. An increased proportion of An. arabiensis was observed compared to previous studies. CONCLUSION: These results suggest that long-term monitoring of larval habitats can establish effective surveillance systems and tools. Additionally, the results suggest that larval control is most effective in the dry season due to habitat restriction, with abandoned goldmines, drainage ditches and swamps being the best habitats to target. Both farmland and pasture should be targeted for effective larval control. An increased proportion of An. arabiensis in the An. gambiae complex was noticed in this study for the very first time in the western Kenya highlands; hence, further control tools should be in place for effective control of An. arabiensis. PMID- 26142905 TI - CRABP1 is associated with a poor prognosis in breast cancer: adding to the complexity of breast cancer cell response to retinoic acid. AB - BACKGROUND: Clinical trials designed to test the efficacy of retinoic acid (RA) as an adjuvant for the treatment of solid cancers have been disappointing, primarily due to RA resistance. Estrogen receptor (ER)-negative breast cancer cells are more resistant to RA than ER-positive cells. The expression and subcellular distribution of two RA-binding proteins, FABP5 and CRABP2, has already been shown to play critical roles in breast cancer cell response to RA. CRABP1, a third member of the RA-binding protein family, has not previously been investigated as a possible mediator of RA action in breast cancer. METHODS: CRABP1 and CRABP2 expression in primary breast tumor tissues was analyzed using gene expression and tissue microarrays. CRABP1 levels were manipulated using siRNAs and by transient overexpression. RA-induced subcellular translocation of CRABPs was examined by immunofluorescence microscopy and immunoblotting. RA induced transactivation of RAR was analyzed using a RA response element (RARE) driven luciferase reporter system. Effects of CRABP1 expression and RA treatment on downstream gene expression were investigated by semi-quantitative RT-PCR analysis. RESULTS: Compared to normal mammary tissues, CRABP1 expression is significantly down-regulated in ER+ breast tumors, but maintained in triple negative breast cancers. Elevated CRABP1 levels are associated with poor patient prognosis, high Ki67 immunoreactivity and high tumor grade in breast cancer. The prognostic significance of CRABP1 is attributed to its cytoplasmic localization. We demonstrate that CRABP1 expression attenuates RA-induced cell growth arrest and inhibits RA signalling in breast cancer cells by sequestering RA in the cytoplasm. We also show that CRABP1 affects the expression of genes involved in RA biosynthesis, trafficking and metabolism. CONCLUSIONS: CRABP1 is an adverse factor for clinical outcome in triple-negative breast cancer and a potent inhibitor of RA signalling in breast cancer cells. Our data indicate that CRABP1, in conjunction with previously identified CRABP2 and FABP5, plays a key role in breast cancer cell response to RA. We propose that these three RA-binding proteins can serve as biomarkers for predicting triple-negative breast cancer response to RA, with elevated levels of either cytoplasmic CRABP1 or FABP5 associated with RA resistance, and elevated levels of nuclear CRABP2 associated with sensitivity to RA. PMID- 26142907 TI - Using of TiN-nanotubes and Cu-nanoparticles for conversion of CO2 to hydrocarbon fuels. AB - In this study, conversion of CO2 and H2O to CH3OH or CH4 on Cu-nanoparticles in TiN- nanotubes was optimized by density functional theory (DFT) methods. DFT optimized the intermediates and transient states using the GAMESS program package, but the structures, total energy, and thermodynamic properties were calculated by semi-empirical methods using ZINDO/1 at room temperature. The results show a sensitivity enhancement in resistance and capacitance when CO2 and H2O are converted to CH3OH and other products. TiN-nanotubes use photo-catalytic reactivity for the reduction of CO2 and H2O to form CH3OH or CH4 at 298 K. The endohedral location of interaction of these reactants in TiN-nanotubes with Cu nanoparticles was investigated. Calculations show that these processes were endothermic, thus the reactions need solar or other energies in the presence of visible light to progress favorably. PMID- 26142906 TI - Recasting brain-machine interface design from a physical control system perspective. AB - With the goal of improving the quality of life for people suffering from various motor control disorders, brain-machine interfaces provide direct neural control of prosthetic devices by translating neural signals into control signals. These systems act by reading motor intent signals directly from the brain and using them to control, for example, the movement of a cursor on a computer screen. Over the past two decades, much attention has been devoted to the decoding problem: how should recorded neural activity be translated into the movement of the cursor? Most approaches have focused on this problem from an estimation standpoint, i.e., decoders are designed to return the best estimate of motor intent possible, under various sets of assumptions about how the recorded neural signals represent motor intent. Here we recast the decoder design problem from a physical control system perspective, and investigate how various classes of decoders lead to different types of physical systems for the subject to control. This framework leads to new interpretations of why certain types of decoders have been shown to perform better than others. These results have implications for understanding how motor neurons are recruited to perform various tasks, and may lend insight into the brain's ability to conceptualize artificial systems. PMID- 26142909 TI - Thoracic Surgery Social Media Network: Bringing Thoracic Surgery Scholarship to Twitter. PMID- 26142908 TI - Tissue-specific autophagy responses to aging and stress in C. elegans. AB - Cellular function relies on a balance between protein synthesis and breakdown. Macromolecular breakdown through autophagy is broadly required for cellular and tissue development, function, and recovery from stress. While Caenorhabditis elegans is frequently used to explore cellular responses to development and stress, the most common assays for autophagy in this system lack tissue-level resolution. Different tissues within an organism have unique functional characteristics and likely vary in their reliance on autophagy under different conditions. To generate a tissue-specific map of autophagy in C. elegans we used a dual fluorescent protein (dFP) tag that releases monomeric fluorescent protein (mFP) upon arrival at the lysosome. Tissue-specific expression of dFP::LGG-1 revealed autophagic flux in all tissues, but mFP accumulation was most dramatic in the intestine. We also observed variable responses to stress: starvation increased autophagic mFP release in all tissues, whereas anoxia primarily increased intestinal autophagic flux. We observed autophagic flux with tagged LGG 1, LGG-2, and two autophagic cargo reporters: a soluble cytoplasmic protein, and mitochondrial TOMM-7. Finally, an increase in mFP in older worms was consistent with an age-dependent shift in proteostasis. These novel measures of autophagic flux in C. elegans reveal heterogeneity in autophagic response across tissues during stress and aging. PMID- 26142910 TI - Validation of the French version of the P-QoL questionnaire. AB - OBJECTIVE: The aim of this study was to validate a French version of the prolapse quality-of-life-questionnaire (P-QoL). STUDY DESIGN: The P-QoL was translated into French and administered to patients recruited in a tertiary referral teaching Hospital. The women concomitantly had a vaginal exam in supine position in order to determine prolapse stage using Pelvic Organ prolapse quantification system (POP-Q). The reliability was assessed by calculating Cronbach's alpha and by performing a test-retest analysis. The validity was evaluated by comparing scores for symptoms and quality of life between symptomatic and asymptomatic women as well as by comparing symptom scores with prolapse stages. RESULTS: 25 symptomatic and 22 asymptomatic patients were included. Cronbach's alphas and the test-retest analysis showed acceptable internal consistency within the domains. The total scores for seven P-QoL domain were significantly different between symptomatic and asymptomatic women (p<0.005). The scores of P-QoL were well correlated with the vaginal examination findings among the symptomatic group (p<0.05 in seven domains). CONCLUSION: The French version of P-QoL is a reliable, valid, and easily comprehensible instrument to assess quality of life and symptoms in women with pelvic organ prolapse. PMID- 26142911 TI - Immature teratoma of ovary--outcome following primary and secondary surgery: study of a single institution cohort. AB - OBJECTIVE: To analyse the clinical presentation, treatment - primary and secondary debulking and outcomes with focus on recurrences in ovarian immature teratoma. STUDY DESIGN: This is a single institution, retrospective analysis of 24 women who presented to a gynecologic oncology unit from 1999 to 2011 with ovarian immature teratoma. Patient's clinical presentation, operative and chemotherapy details were included in a database. Follow up details regarding recurrence and management and future outcomes were also noted. Overall survival was calculated from the date of registration to last follow up or date of death. Survival curve was constructed by Kaplan-Meier method. RESULTS: Immature teratoma accounted for 11% of 218 malignant germ cell tumors. Of the 24 patients, pain was the predominant symptom and abdominal mass was the commonest clinical presentation. Sixteen out of 24 patients presented in Stage I and grade 3 tumors were found in 43% of patients. Six patients had only unilateral salpingo oophorectomy and no staging procedure. Twelve patients underwent staging, with omentectomy being the commonest procedure. All but one, had cisplatin based combination chemotherapy. Six patients underwent secondary debulking of recurrence. Most recurrences were recorded in Stage III, higher grade tumors. With secondary cytoreduction and platinum based chemotherapy, it was possible to salvage most recurrences as well. Overall survival after a mean follow-up of 39 months was 91.6%. CONCLUSION: Majority of the patients did well with conservative surgery in terms of survival, menstrual and reproductive function. Platinum based chemotherapy was indicated in higher grade and higher stage tumors as recurrences commonly occurred in this subgroup of patients. Recurrences could be salvaged with selected secondary cytoreduction and platinum based chemotherapy. PMID- 26142912 TI - Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study. AB - OBJECTIVE: To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas. STUDY DESIGN: Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n=23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n=20), letrozole (2.5 mg/day; group L; n=11) or ulipristal acetate (5 mg/day; group U; n=7). Patients underwent hysteroscopic resection of the myomas. RESULTS: All medical treatments caused a significant decrease in the volume of myomas (group T, p<.001; group L, p<.001; group U, p=.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p=.001) and in group L (p=.010). The hysteroscopy time was higher in group S than in group T (p<.001) and in group L (p=.001); there was no significant difference in the hysteroscopy time between group S and group U (p=.206). Fluid absorption was lower in group T than in group S (p=.002) and in group L than in group S (p=.048); fluid absorption was similar in group S and group U (p=.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeon's evaluation of operative difficulty was better in group T than in group S (p<.005). CONCLUSIONS: Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas. PMID- 26142913 TI - Management of severe fetal anemia by Doppler measurement of middle cerebral artery: are there other benefits than reducing invasive procedures? AB - OBJECTIVE: Doppler measurement of peak velocity of systolic blood flow in the middle cerebral artery (PVS-MCA) can safely replace invasive testing in the diagnosis of fetal anemia in Rh-alloimmunized pregnancies and PSV-MCA is now the reference technique. However, no study has evaluated its impact in antenatal care and in survival rate. Our objective was to evaluate the impact of the measurement of PVS-MCA in antenatal management and neonatal outcome in maternal red cell alloimmunization requiring in utero transfusion (IUT). STUDY DESIGN: Retrospective study between January 1999 and January 2013. We excluded all cases of hydrops without follow-up before first IUT. From 1999 to 2006, an IUT was indicated on the optical index at 450 nm (Period 1) and was then replaced by the use of PVS-MCA (Period 2). RESULTS: 77 patients were included, 39 in Period 1 (104 IUT) and 38 in Period 2 (89 IUT). 5 cases of hydrops fetalis (12.8%) were diagnosed during the follow up in Period 1 and none during Period 2. The average number of IUT, the delays between 2 IUT and between last IUET and birth were comparable. The total rate of complication per IUT during the first period was 9.6% vs 1.1% during the second one (p=0.01). The overall survival rate in our population was 34/39 (86.8%) during Period 1 vs 38/38 (100%) during Period 2. CONCLUSION: PSV-ACM allowed an improved monitoring with fewer occurrences of hydrops. Conversely, it did not modify antenatal management and timing of delivery. PMID- 26142914 TI - Impact of lower limb lymphedema on quality of life in gynecologic cancer survivors after pelvic lymph node dissection. AB - OBJECTIVE: To evaluate the impact of lower limb lymphedema (LLL) on quality of life (QOL) in cervical, ovarian, and endometrial cancer survivors after pelvic lymph node dissection. STUDY DESIGN: A cross-sectional case-control study was performed using the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). In total, 25 women with LLL and 28 women without LLL completed both questionnaires. RESULTS: The GCLQ-K total symptom score and scores for swelling-general, swelling-limb, and heaviness were significantly higher in the LLL group than in the control group. In the EORTC QLQ-C30, the LLL group reported more financial difficulties compared to the control group (mean score, 16.0 vs. 6.0; P=0.035). Global health status was poorer in the LLL group with borderline statistical significance (mean score, 62.7 vs. 71.4; P=0.069). Spearman's correlations suggested that global health status in the EORTC QLQ-C30 correlated with the GCLQ-K total symptom score (in the LLL group, R=-0.64, P=0.001; in the control group, R=-0.42, P=0.027). CONCLUSIONS: QOL decreases due to LLL-related symptoms and financial difficulty in women with LLL. Well-designed prospective studies are required to confirm these findings. PMID- 26142915 TI - Sexual abuse predicts functional somatic symptoms: an adolescent population study. AB - The main aim of this study was to investigate the effect of childhood sexual abuse on medically not well explained or functional somatic symptoms (FSSs) in adolescents. We hypothesized that sexual abuse predicts higher levels of FSSs and that anxiety and depression contribute to this relationship. In addition, we hypothesized that more severe abuse is associated with higher levels of FSSs and that sexual abuse is related to gastrointestinal FSSs in particular. This study was part of the Tracking Adolescents' Individual Lives Survey (TRAILS): a general population cohort which started in 2001 (N=2,230; 50.8% girls, mean age 11.1 years). The current study uses data of 1,680 participants over four assessment waves (75% of baseline, mean duration of follow-up: 8 years). FSSs were measured by the Somatic Complaints subscale of the Youth Self-Report at all waves. Sexual abuse before the age of sixteen was assessed retrospectively with a questionnaire at T4. To test the hypotheses linear mixed models were used adjusted for age, sex, socioeconomic status, anxiety and depression. Sexual abuse predicted higher levels of FSSs after adjustment for age sex and socioeconomic status (B=.06) and after additional adjustment for anxiety and depression (B=.03). While sexual abuse involving physical contact significantly predicted the level of FSSs (assault; B=.08, rape; B=.05), non-contact sexual abuse was not significantly associated with FSSs (B=.04). Sexual abuse was not a stronger predictor of gastrointestinal FSSs (B=.06) than of all FSSs. Further research is needed to clarify possible mechanisms underlying relationship between sexual abuse and FSSs. PMID- 26142916 TI - Predictive analytics and child protection: constraints and opportunities. AB - This paper considers how predictive analytics might inform, assist, and improve decision making in child protection. Predictive analytics represents recent increases in data quantity and data diversity, along with advances in computing technology. While the use of data and statistical modeling is not new to child protection decision making, its use in child protection is experiencing growth, and efforts to leverage predictive analytics for better decision-making in child protection are increasing. Past experiences, constraints and opportunities are reviewed. For predictive analytics to make the most impact on child protection practice and outcomes, it must embrace established criteria of validity, equity, reliability, and usefulness. PMID- 26142917 TI - Molecular dynamics simulation study reveals potential substrate entry path into gamma-secretase/presenilin-1. AB - Presenilin 1 (PS1) is the catalytic unit of gamma-secretase which cleaves more than one hundred substrates. Among them, amyloid precursor protein (APP) and Notch are notable for their pivotal role in the pathogenesis of Alzheimer's disease (AD) and certain types of cancer. The hydrolysis process occurring inside the hydrophobic lipid bilayer remains unclear. With the aim to understand the mechanism of intramembrane proteolysis by gamma-secretase, we constructed a homology model of human PS1 and performed molecular dynamics simulation in explicit membrane phospholipids with different components. During the simulation, TM9 was found to exhibit a high level of flexibility that involved in "gate-open" movement of TM2 and TM6, and thus partially exposed the catalytic residues. The highly conserved PALP motif acts as an anchor to mediate the conformation changes of TM6 induced by TM9. Moreover, direct interactions were observed between 1 palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and the active site of gamma-secretase, indicating that the lipid molecules have the potential to modulate gamma-secretase by contacting with the catalytic residues, i.e., ASP 257 and ASP 385 of PS1. The intermediate states indicate a potential substrate penetration pathway through the interface of TM2 and TM6, which may be induced by changes of TM9. To our knowledge, this is the first molecular simulation study that reveals dynamic behavior of the human PS1 structure in the lipid bilayer and provides insight into the substrate entry path for subsequent intramembrane hydrolysis, which is critical information required for new strategy development of gamma-secretase modulators to alleviate devastating AD. PMID- 26142918 TI - Letter to the Editor on Cohen et al. (Letter commenting on: J Clin Epidemiol. 2015;68:299-306). PMID- 26142919 TI - Design of stepwise screening for prediabetes and type 2 diabetes based on costs and cases detected. AB - OBJECTIVES: To provide insight into the trade-off between cost per case detected (CPCD) and the detection rate in questionnaire-based stepwise screening for impaired fasting glucose and undiagnosed type 2 diabetes. STUDY DESIGN AND SETTING: We considered a stepwise screening in which individuals whose risk score exceeds a predetermined cutoff value are invited for further blood glucose testing. Using individual patient data to determine questionnaire sensitivity and specificity and external sources to determine screening costs and patient response rates, we rolled back a decision tree to estimate the CPCD and the detection rate for all possible cutoffs on the questionnaire. RESULTS: We found a U-shaped relation between CPCD and detection rate, with high costs per case detected at very low and very high detection rates. Changes in patient response rates had a large impact on both the detection rate and the CPCD, whereas screening costs and questionnaire accuracy mainly impacted the CPCD. CONCLUSION: Our applied method makes it possible to identify a range of efficient cutoffs where higher detection rates can be achieved at an additional cost per detected patient. This enables decision makers to choose an optimal cutoff based on their willingness to pay for additional detected patients. PMID- 26142920 TI - Unidirectional flow in lizard lungs: a paradigm shift in our understanding of lung evolution in Diapsida. AB - Conventional wisdom has held that unidirectional pulmonary airflow is unique to birds and is an adaption enabling high rates of gas exchange, essential for sustaining flight as well as an endothermic metabolism. Recent visualizations and measurements of flow in the lungs of monitor and iguanid lizards show a bird-like pattern of unidirectional flow in these lineages. These findings call for a paradigm shift in our understanding of lung evolution in diapsids. This pattern of flow is not unique to birds. It is much older than previously believed, and it may be advantageous to the low-energy lifestyles typical of ectothermic animals. PMID- 26142921 TI - Response to Rougeron et al.: Leishmania population genetics: clonality, selfing and aneuploidy. PMID- 26142922 TI - Response to Tibayrenc et al.: can recombination in Leishmania parasites be so rare? PMID- 26142923 TI - The gut microbiome in the helminth infected host. AB - Two kinds of organism that affect human nutrition and health are gut bacteria and intestinal helminths. The interaction between helminths and gut bacteria is currently a subject of much research interest and speculation in terms of host health. This is unsurprising given the excitement stimulated by potential therapeutic interventions that could arise from manipulating the gut microbiome structure. PMID- 26142924 TI - Real-life Experience: Early Recurrence With Hexvix Photodynamic Diagnosis assisted Transurethral Resection of Bladder Tumour vs Good-quality White Light TURBT in New Non-muscle-invasive Bladder Cancer. AB - OBJECTIVE: To compare early recurrence between good-quality white-light transurethral resection of bladder tumor (GQ-WLTURBT) and photodynamic diagnosis assisted (PDD) transurethral resection of bladder tumor (TURBT) in a real-life controlled setting. METHODS: A prospective controlled study was conducted commencing with a planned prospective cohort of patients with new tumors undergoing white-light TURBT in 2007-2008. Previously defined principles of GQ WLTURBT for standardization and comparison of TURBT techniques, which are (1) cystoscopic mapping using a bladder diagram, (2) documented complete resection of the tumor, (3) resection performed or supervised by an experienced surgeon, (4) presence of detrusor muscle in the specimen, and (5) patient receiving mitomycin C within 24 hours of the resection, were applied. This was followed by a prospective cohort of new patients undergoing PDD-TURBT in 2009-2011. Only patients with new non-muscle-invasive bladder cancer (NMIBC) deemed to have had complete first TURBT were included for analysis. Tumor features and findings at first check cystoscopy and early re-TURBT (in high-risk NMIBC) were evaluated. Early recurrence (for calculating recurrence rate at first follow-up cystoscopy) was defined as pathologically confirmed tumor on early re-TURBT or recurrence at the first check cystoscopy. Comparison was analyzed between GQ-WLTURBT and good quality PDD-TURBT (GQ-PDDTURBT). RESULTS: A total of 808 patients were evaluated. The overall RRFFCs for GQ-WLTURBT and GQ-PDDTURBT were 30.9% and 13.6%, respectively (odds ratio = 2.9; 95% CI = 1.6-5.0; P <.001), with statistically significant lower recurrence rates in low- and intermediate-risk NMIBC after GQ PDDTURBT. CONCLUSION: Hexvix PDD-assisted TURBT is associated with a significantly lower risk of early recurrence compared with GQ-WLTURBT in a real life clinical setting. PMID- 26142925 TI - Are sunscreens a new environmental risk associated with coastal tourism? AB - The world coastal-zone population and coastal tourism are expected to grow during this century. Associated with that, there will be an increase in the use of sunscreens and cosmetics with UV-filters in their formulation, which will make coastal regions worldwide susceptible to the impact of these cosmetics. Recent investigations indicate that organic and inorganic UV-filters, as well as many other components that are constituents of the sunscreens, reach the marine environment--directly as a consequence of water recreational activities and/or indirectly from wastewater treatment plants (WWTP) effluents. Toxicity of organic and inorganic UV filters has been demonstrated in aquatic organism. UV-filters inhibit growth in marine phytoplankton and tend to bioaccumulate in the food webs. These findings together with coastal tourism data records highlight the potential risk that the increasing use of these cosmetics would have in coastal marine areas. Nevertheless, future investigations into distribution, residence time, aging, partitioning and speciation of their main components and by-products in the water column, persistence, accumulation and toxicity in the trophic chain, are needed to understand the magnitude and real impact of these emerging pollutants in the marine system. PMID- 26142926 TI - Skewed distribution of hypothyroidism in the coastal communities of Newfoundland, Canada. AB - Several studies published in the recent past have shown that rising levels of thyroid disrupting chemicals (TDCs) in the environment affect thyroid function in humans. These TDCs are the anthropogenic organic compounds that enter the human body mostly by ingestion and may trigger autoimmune thyroiditis, the most common cause of hypothyroidism. The studies also show the presence of high levels of TDCs in marine animals; therefore, consumption of contaminated seafood might trigger hypothyroidism. So far, there is no readily available population-based data, showing the regional distribution of hypothyroidism cases. We collected administrative data from the Newfoundland and Labrador Centre for Health Information on hospitalizations with hypothyroidism (from 1998 to 2012) in 41 coastal communities of Newfoundland and found that mean hypothyroidism rates of west and south coasts were significantly higher than in the east coast (1.8 and 1.9 times respectively). A one-way analysis of variance was used to test for regional differences in rates. A significant between-group difference in the rate of hypothyroidism was found (F2,38 = 8.309; p = 0.001). The St. Lawrence River, its estuary and the Gulf of St. Lawrence are heavily polluted with TDCs from industries, their effluents, and urbanization in the Great Lakes Watershed and along the river. Environment Canada has already identified this river along with the Great Lakes Watershed as one of the top TDCs polluted water sources in the country. The west and south coasts are in contact with the Gulf of St. Lawrence. Local marine products are a regular diet of the coastal communities of Newfoundland. Based on these available evidence, we hypothesize the role of TDCs in the rise of hypothyroidism on the western and southern coasts. However, further study will be needed to establish any association between abnormally high rates of hypothyroidism and exposure to TDCs. PMID- 26142927 TI - ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells. AB - Proteostasis is crucial for life and maintained by cellular chaperones and proteases. One major mitochondrial protease is the ClpXP complex, which is comprised of a catalytic ClpX subunit and a proteolytic ClpP subunit. Based on two separate observations, we hypothesized that ClpX may play a leading role in the cellular function of ClpXP. Therefore, we analyzed the effect of ClpX overexpression on a myoblast proteome by quantitative proteomics. ClpX overexpression results in the upregulation of markers of the mitochondrial proteostasis pathway, known as the "mitochondrial unfolded protein response" (UPRmt). Although this pathway is described in detail in Caenorhabditis elegans, it is not clear whether it is conserved in mammals. Therefore, we compared features of the classical nematode UPRmt with our mammalian ClpX-triggered UPRmt dataset. We show that they share the same retrograde mitochondria-to-nucleus signaling pathway that involves the key UPRmt transcription factor CHOP (also known as Ddit3, CEBPZ or GADD153). In conclusion, our data confirm the existence of a mammalian UPRmt that has great similarity to the C. elegans pathway. Furthermore, our results illustrate that ClpX overexpression is a good and simple model to study the underlying mechanisms of the UPRmt in mammalian cells. PMID- 26142928 TI - A Markov random field approach to group-wise registration/mosaicing with application to ultrasound. AB - In this paper we present a group-wise non-rigid registration/mosaicing algorithm based on block-matching, which is developed within a probabilistic framework. The discrete form of its energy functional is linked to a Markov Random Field (MRF) containing double and triple cliques, which can be effectively optimized using modern MRF optimization algorithms popular in computer vision. Also, the registration problem is simplified by introducing a mosaicing function which partitions the composite volume into regions filled with data from unique, partially overlapping source volumes. Ultrasound confidence maps are incorporated into the registration framework in order to give accurate results in the presence of image artifacts. The algorithm is initially tested on simulated images where shadows have been generated. Also, validation results for the group-wise registration algorithm using real ultrasound data from an abdominal phantom are presented. Finally, composite obstetrics image volumes are constructed using clinical scans of pregnant subjects, where fetal movement makes registration/mosaicing especially difficult. In addition, results are presented suggesting that a fusion approach to MRF registration can produce accurate displacement fields much faster than standard approaches. PMID- 26142929 TI - Exercise does not enhance aged bone's impaired response to artificial loading in C57Bl/6 mice. AB - Bones adapt their structure to their loading environment and so ensure that they become, and are maintained, sufficiently strong to withstand the loads to which they are habituated. The effectiveness of this process declines with age and bones become fragile fracturing with less force. This effect in humans also occurs in mice which experience age-related bone loss and reduced adaptation to loading. Exercise engenders many systemic and local muscular physiological responses as well as engendering local bone strain. To investigate whether these physiological responses influence bones' adaptive responses to mechanical strain we examined whether a period of treadmill exercise influenced the adaptive response to an associated period of artificial loading in young adult (17-week) and old (19-month) mice. After treadmill acclimatization, mice were exercised for 30 min three times per week for two weeks. Three hours after each exercise period, right tibiae were subjected to 40 cycles of non-invasive axial loading engendering peak strain of 2250 MUepsilon. In both young and aged mice exercise increased cross-sectional muscle area and serum sclerostin concentration. In young mice it also increased serum IGF1. Exercise did not affect bone's adaptation to loading in any measured parameter in young or aged bone. These data demonstrate that a level of exercise sufficient to cause systemic changes in serum, and adaptive changes in local musculature, has no effect on bone's response to loading 3h later. This study provides no support for the beneficial effects of exercise on bone in the elderly being mediated by systemic or local muscle-derived effects rather than local adaptation to altered mechanical strain. PMID- 26142930 TI - Association between femur size and a focal defect of the superior femoral neck. AB - Within each sex, there is an association between hip fracture risk and the size of the proximal femur, with larger femurs apparently more susceptible to fracture. Here, we investigate whether the thickness and density of the femoral cortex play a role in this association: might larger femurs harbour focal, cortical defects? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm(2)) in cohorts of 308 males and 125 females. Principal component analysis of the various femoral surfaces led to a measure of size that is linearly independent from shape. After mapping the data onto a canonical femur surface, we used statistical parametric mapping to identify any regions where CMSD depends on size, allowing for other confounding covariates including shape. Our principal finding was a focal patch on the superior femoral neck, where CMSD is reduced by around 1% for each 1% increase in proximal-distal size (p<0.000005 in the males, p<0.001 in the females). This finding appears to be consistent with models of functional adaptation, and may help with the design of interventional strategies for reducing fracture risk. PMID- 26142932 TI - Effects of a 10-day course of a high dose calciferol versus a single mega dose of ergocalciferol in correcting vitamin D deficiency. AB - BACKGROUND AND OBJECTIVES: The correction of vitamin D deficiency is crucial for optimal skeletal and non-skeletal health. Most regimens in current use are based on daily dosing, which may raise concerns of dosage inadequacy and suboptimal patient compliance. Vitamin D is available in 2 forms: D2 (ergocalciferol) and D3 (cholecalciferol). It has been reported that D2 supplements are less effective and may enhance the degradation of 25-hydroxyvitamin D3 (25[OH]D3) metabolite. The aim of this study was to compare the effect of 2 high-dose oral vitamin D regimens--a 10-day course of D3 500,000 IU versus a single mega dose of 600,000 IU D2--on serum 25(OH)D levels. DESIGN AND SETTINGS: A prospective cohort study was conducted from September 2010 to February 2011 in an urban university tertiary hospital in Amman, Jordan. PATIENTS AND METHODS: A total of 109 patients aged 18 to 79 years were enrolled with severe vitamin D deficiency. Fifty-one subjects received 600,000 IU D2 orally and 54 subjects received a total dose of 500,000 IU D3 administered orally, as 50,000 IU D3 daily for 10 consecutive days. Baseline and follow-up total serum 25(OH)D, 25(OH)D2, and 25(OH)D3 levels were compared. RESULTS: The mean total 25(OH)D increment from baseline was 10.33 (5.68) ng/mL over a mean of 43.08 (2.81) days for the D2 group. The mean increment in 25(OH)D for the D3 group was 47.03 (23.67) ng/mL over a mean of 36.9 (2.9) days. The difference between the 2 mean increments was highly significant: P=3.15.10-18. The 600,000 IU D2 single mega-dose decreased 25(OH)D3 levels by an average of 4 ng/mL in 37 subjects. CONCLUSION: Overall, the 10-day oral D3 regimen rapidly and effectively normalized 25(OH)D levels. The shortened dosing interval over 10 consecutive days might result in higher compliance. PMID- 26142933 TI - Characteristics of pediatric ulcerative colitis in Saudi Arabia: a multicenter national study. AB - BACKGROUND: Despite the extensive reporting of pediatric ulcerative colitis (UC) from industrialized developed countries, reports from developing countries are limited to small-case series from single centers. The objective of our large multicenter study was to determine the clinical, laboratory, endoscopic characteristics of UC in children from a developing country, Saudi Arabia. DESIGN AND SETTINGS: A retrospective study of children diagnosed with UC under the age of 18 years during the period from 2003 to 2012. METHODS: Patients enrolled from 15 medical centers from different regions in Saudi Arabia. A unified database collection form specifically designed for this study was completed by all participating centers. RESULTS: A total of 188 children were diagnosed with UC during the study period (97 males [51.6%] and 91 females [48.4%]). The mean age at diagnosis was 9.1 years, and the mean duration of symptoms before diagnosis was 8.7 months. Consanguinity was present in 57 cases (32.6%), and the family history of inflammatory bowel disease (IBD) was noted in 16 cases (9%). The most common clinical presentation was blood in stool (90%), followed by diarrhea (86%) and abdominal pain (62%). Laboratory investigations revealed elevated erythrocyte sedimentation rate (82%), anemia (75%), thrombocytosis (72%), and hypoalbuminemia (33%). The extent of the disease was pan colonic in 46.1%, and confined to left side of colon and rectum in 23% and 9.6% of the cases, respectively. CONCLUSION: This demographically pediatric IBD retrospective study revealed age-related variation in the distribution of IBD. Clinical presentation, with a high prevalence of positive consanguinity and positive family history, was noted in young patients with UC. The data from this study indicate that UC is increasingly recognized in Saudi Arabia and show many similarities to data from North America and Europe. PMID- 26142931 TI - 2015 Guidelines for Osteoporosis in Saudi Arabia: Recommendations from the Saudi Osteoporosis Society. AB - BACKGROUND AND OBJECTIVES: To provide guidelines for medical professionals in Saudi Arabia regarding osteoporosis. DESIGN AND SETTINGS: A panel of 14 local experts in osteoporosis assembled to provide consensus based on the strength of evidence and expert opinions on osteoporosis treatment. PATIENTS AND METHODS: The Saudi Osteoporosis Society (SOS) formed a panel of experts who performed an extensive published studies search to formulate recommendations regarding prevention, diagnosis, and treatment of osteoporosis in Saudi Arabia. Both local and international published studies were utilized whenever available. RESULTS: Dual x-ray absorptiometry (DXA) scanning is still the golden standard for assessing bone mineral density (BMD). In the absence of local, country-specific fracture risk assessment tool (FRAX), the SOS recommends using the USA (White) version of the FRAX tool. All women above 60 years of age should be evaluated for BMD. This is because the panel recognized that osteoporosis and osteoporotic fractures occur at a younger age in Saudi Arabia. Hormone replacement therapy (HRT) is not recommended for treating postmenopausal women with osteoporosis. BMD evaluation should be performed 1-2 years after initiating intervention, and the assessment of bone turnover biomarkers should be performed whenever available to determine the efficacy of intervention. CONCLUSION: All Saudi women above the age of 60 years must undergo a BMD assessment using DXA. Therapy decisions should be formulated with the use of the USA (White) version of the FRAX tool. PMID- 26142934 TI - Five-year outcomes of preoperative chemoradiation for rectal carcinoma in Saudi population: single-institutional experience. AB - OBJECTIVES: Preoperative chemoradiation (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). The outcomes of preoperative CRT in Saudi patients with LARC have not been widely studied. The study reports long-term outcomes after preoperative CRT followed by curative surgery in Saudi patients with LARC. DESIGN AND SETTINGS: A retrospective, single-institutional study performed in the tertiary care oncology center in Saudi Arabia. MATERIALS AND METHODS: A total of 154 out of 204 patients with LARC were treated with preoperative CRT and followed by surgery at the oncology center between September 2005 and November 2012. Data regarding the response rates, toxicity profile, locoregional control (LRC), distant metastasis control (DMC), overall survival (OS), and disease-free survival (DFS) rates were analyzed. RESULTS: The median age of the study population was 56.6 years (range: 26-89). Predominant clinical stages were IIA (70 patients; 45.4%) and IIIB (49 patients; 31.8%). Majority of patients (79.8%) underwent a complete total mesorectal excision (TME). Complete pathological response (ypT0N0) was seen in 26 patients (16.8%). At 5 years, locoregional recurrence (LR) was reported in 12 patients (7.8%), and distant metastases were noted in 33 patients (21.4%). The 5-year cumulative LRC, DMC, OS, and DFS rates were 91%, 71.3%, 78%, and 64.8%, respectively. Stage, nodal status, circumferential margins, ypT0N0, and adjuvant chemotherapy were found to be important prognostic factors for DFS. CONCLUSION: The results of preoperative CRT followed by surgery and adjuvant chemotherapy in Saudi population are comparable with international data. PMID- 26142935 TI - Gastrointestinal symptoms are closely associated with depression in iron deficiency anemia: a comparative study. AB - BACKGROUND AND OBJECTIVES: Until now, very few studies evaluated the association between gastrointestinal and psychiatric symptoms in iron deficiency anemia (IDA). The study investigated the frequency of functional dyspepsia (FD) in IDA patients and determined its association with depression and somatization. DESIGN AND SETTINGS: The study was conducted at the Hematology Department of Trakya University Medical Faculty, which is a tertiary referral center in northwestern Turkey. It was a case-control study. MATERIALS AND METHODS: A total of 125 consecutive IDA patients and 57 healthy control subjects were included. Patients and controls were questioned about the severity of their gastrointestinal system (GIS)-related symptoms and the presence of constipation and associated symptoms using a visual analog scale. In addition, IDA patients were administered a validated depression scale (Beck Depression Inventory, BDI) and somatization symptoms checklist. RESULTS: IDA patients had more frequent self-reported constipation compared with controls (56% vs 22.8%, P < .001). The mean scores of bloating, dyspepsia, and constipation-related quality of life (QoL) disturbance were significantly higher in the IDA group than in the control group (all P values. PMID- 26142936 TI - Aneurysmal subarachnoid hemorrhage affects the younger age groups in a Saudi academic center. AB - BACKGROUND AND OBJECTIVES: The epidemiology, clinical characteristics, and risk factors of aneurysmal subarachnoid hemorrhage (aSAH) in Saudi Arabia are still largely unknown. This retrospective cohort study was aimed to determine these features of the disease. DESIGN AND SETTINGS: A retrospective cohort review was performed on all patients with aSAH who were treated and followed at King Abdulaziz University Hospital between July 2000 and December 2013. PATIENTS AND METHODS: A quantitative methodology was used and data were collected on patients' age, gender, nationality, time to hospital presentation, clinical presentation, aneurysm characteristics, treatment, complications, and outcome. RESULTS: A total of 41 patients with aSAH were included with a mean age of 43.2 (11.5) years; and males comprised 34.1%. Smoking and hypertension were the most common risk factors. Eight patients had known risk factors for aSAH, and were diagnosed using CT scans. An unfavorable outcome was associated with the presence of vasospasm (P < .001), cerebral edema (P=.001), and hydrocephalus (P=.003). CONCLUSION: A high occurrence of aSAH was observed in an age group younger than that reported in published reports. The pattern and outcome of aSAH were otherwise similar to prior reports. Future studies investigating these observations in other centers in the country can improve the prevention and treatment of this serious condition. PMID- 26142937 TI - Vagus nerve stimulation for refractory epilepsy: experience from Saudi Arabia. AB - BACKGROUND: Vagus nerve stimulation (VNS) has been approved for the treatment of refractory partial epilepsy in adults and children over 12 years of age. Later on, its application expanded to include younger children and other types of epilepsy. We report our experience with this treatment modality for refractory epilepsy in Saudi Arabia. DESIGN AND SETTINGS: Open-label, uncontrolled, retrospective study of patients with refractory epilepsy, who were treated with VNS in a tertiary care hospital from January 2010 to June 2013. PATIENTS AND METHODS: Collected data included 26 patients' demographics, epilepsy characteristics, seizure frequency, and treatment history. Patients with a follow up duration of minimum 12 months were included in the analysis. The examined outcome measures were seizure reduction rates, antiepileptic drugs (AEDs) burden, and impact on patients' quality of life (QOL). RESULTS: Onset of seizures was from birth to 30 years. Patients' ages at VNS implantation ranged from 4 to 38 years (18.9 [8.7] years). Epilepsy was classified as focal in 8 patients (30%), multifocal in 9 patients (35%), and generalized in 9 patients (35%). The average number of AEDs failed before VNS was 4.2 (1.4). Greater than 50% seizure reduction was achieved in 50% of patients at 3 months, 67% at 6 months, 73% at 12 months, and 78% at 24 months. There was no significant reduction in AEDs burden during the same period. Subjective QOL improvement was reported by 72% of patients at 3 months, 83% at 6 months, 78% at 12 months, and 73% at 24 months after VNS. Minor adverse effects were reported in 27% of patients. One patient had the device replaced due to malfunction. CONCLUSION: The experience with VNS in a single center in Saudi Arabia confirms that it is a safe and effective adjunctive therapy for refractory epilepsy in adult and pediatric patients. PMID- 26142938 TI - Predictors of global job satisfaction among Saudi physiotherapists: a descriptive study. AB - BACKGROUND AND OBJECTIVE: Job satisfaction is an important consideration in the recruitment and retention of physiotherapists (PTs). To date, the job satisfaction of PTs working in Saudi Arabia has not been investigated. The aim of this study was to measure the level of job satisfaction of PTs working in Saudi Arabia and evaluate predictors of job satisfaction. DESIGN AND SETTINGS: This was a cross-sectional observational study among licensed physical therapists working across 11 health care centers and university hospitals in Riyadh between 2013 and 2014. SUBJECTS AND METHODS: A total of 183 physical therapists participated in the survey. Level of job satisfaction and factors influencing satisfaction were explored using a purpose-designed job satisfaction questionnaire. It consisted of 8 survey domains, and the scores were normalized to allow between-domain comparison. RESULTS: Global job satisfaction was 37%. The highest levels of job satisfaction were seen in the domains of professional development and teamwork and the lowest levels of job satisfaction in the domains of supervisory/ management relationship (75%) and working environment (60%). Predictors of job satisfaction were gender (OR [odds ratio] 1.4, 95% CI 1.1-2.3), age (OR 0.7, 95% CI 0.5-0.9), relationships with supervisors and managers (OR 1.3, 95% CI 1.2 1.9), working environment (OR 1.2, 95% CI 1.0-2.3), and opportunities for professional development (OR 1.4, 95% CI 1.2-3.7). CONCLUSION: Saudi PTs were moderately satisfied with their job; strategies should be designed in such a way that they experience a high level of job satisfaction and retention thus resulting in improved rehabilitation services in Saudi Arabia. PMID- 26142939 TI - Impact of MTHFR (C677T) gene polymorphism on antiepileptic drug monotherapy in North Indian epileptic population. AB - BACKGROUND AND OBJECTIVES: Antiepileptic drugs (AEDs) are known to interfere with homocysteine metabolism. Hyperhomocysteinemia may be a risk factor associated in the long-term treatment with AEDs. Both genetic and non-genetic factors are responsible for hyperhomocysteinemia. MTHFR C677T polymorphism leads to the reduction in enzyme activity and subsequent elevation of plasma homocysteine. This study aimed to investigate the role of MTHFR C677T polymorphism in epileptic patients receiving AEDs as monotherapy (phenytoin, carbamazepine, and sodium valproate) and showing toxicity and non-toxicity, and the impact of AEDs on hyperhomocysteinemia in North Indian population. DESIGN AND SETTINGS: Blood samples for this case-control study were collected from the outpatient department and wards of the Department of Neurosciences at the All India Institute of Medical Sciences, New Delhi, India, between July 2008 and May 2010. PATIENTS AND METHODS: In this study, 200 epileptic patients and 100 normal controls were assessed for total homocysteine (tHcy), vitamin B12, and folate levels using enhanced chemiluminescence enzyme immunoassay method (ImmuliteR, 1000 systems, DPC, United States); genotyping of MTHFR C677T was done using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The results showed a significant increase in tHcy levels in epileptic patients with toxicity and non-toxicity than in normal controls (P < .005). The allelic and genotypic distributions were found to be statistically significant in toxicity and non toxicity groups (P < .05). CONCLUSION: The result confirmed that hyperhomocysteinemia is common in adults receiving AED treatment for epilepsy with toxicity and non-toxicity groups. This increase in tHcy is mainly related to low folate and vita.min B12 levels, which are the main determinants for tHcy. PMID- 26142940 TI - Hypnosis for sedation in transesophageal echocardiography: a comparison with midazolam. AB - BACKGROUND: Transesophageal echocardiography (TEE), being a displeasing intervention, usually entails sedation. We aimed to compare the effects of hypnosis and midazolam for sedation in TEE. DESIGN AND SETTINGS: A prospective single-blinded study conducted on patients scheduled for TEE between April 2011 and July 2011 at a university in Istanbul, Turkey. METHODS: A total of 41 patients underwent sedation using midazolam and 45 patients underwent hypnosis. Patients were given the State-Trait Anxiety Inventory (STAI) test for anxiety and continuous performance test (CPT) for alertness before and after the procedure. The difficulty of probing and the overall procedure rated by the cardiologist and satisfaction scores of the patients were also documented. RESULTS: Anxiety was found to be less and attention more in the hypnosis group, as revealed by STAI and CPT test scores (P < .05 and P < .001, respectively). CONCLUSION: Hypnosis proved to be associated with positive therapeutic outcomes for TEE with regard to alleviation of anxiety and maintenance of vigilance, thus providing more satisfaction compared to sedation with midazolam. PMID- 26142941 TI - Brain magnetic resonance imaging and proton MR spectroscopic findings after metabolic crisis in 3-methylcrotonylglycinuria. AB - Magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) findings in 3-methylcrotonylglycinuria presenting with acute metabolic decompensation in a previously healthy 7-year old female are described. The patient was hospitalized with fever, irritability, gastrointestinal problems, drowsiness, signs of upper motor neuron deficit, and rapidly progressive respiratory distress requiring assisted ventilation. Laboratory workup showed severe metabolic acidosis, and the diagnosis of 3-methylcrotonylglycinuria was established by the mass spectrometry analysis of urine sample. Although initial CT imaging workup was found to be gross normal, subsequent MRI of the brain in the early chronic stage of the disease showed symmetrical ill-defined signal abnormalities within medulla oblongata, pons, inferior cerebellar peduncles, and periventricular white matter in cerebral hemispheres. Diffusion-weighted images were unremarkable. Single-voxel proton MRS showed elevated levels of lactate, branched-chain amino acids, as well as glutamine and glutamate. To the best of our knowledge, this is the first reported case of late onset 3 methylcrotonylglycinuria with complete MRI and MRS workup in the early chronic phase after metabolic crisis. PMID- 26142942 TI - Acute-onset paralysis in a patient of rheumatoid arthritis. AB - Renal tubular acidosis (RTA) is a disorder of renal acidification characterized by inability to acidify urine to pH < 5.5 despite the presence of severe systemic metabolic acidosis and hypokalemia. Hypokalemia leads to acute-onset paralysis and may be a presenting manifestation of RTA. Its association with various autoimmune disease has been reported previously in published reports, but has not been much emphasized. We, hereby, report a case of RTA that presented during the flare of rheumatoid arthritis (RA). A 42-year-old female, a known case of RA for 5 years, presented with persistent joint pain for 1 week and acute-onset quadriparesis for 3 days. Primary investigations revealed hypokalemia with metabolic acidosis. She was managed conservatively with potassium supplements and bicarbonate supplements along with steroids and disease-modifying anti-rheumatic drugs. Such a presentation of renal tubular acidosis in a patient during the flare of rheumatoid arthritis is distinctly rare and previously unreported in published studies. PMID- 26142943 TI - Multiple hyperplastic nodular lesions of the liver in the Budd-Chari syndrome: a case report and review of published reports. AB - The Budd-Chari syndrome (BCS) is a group of disorders of hepatic vein outflow at various levels from the hepatic veins to inferior vena cave. We describe a 49 year-old man with multiple intrahepatic lesions who had been diagnosed with the BCS. The inferior vena cavography showed hepatic vein occlusion and long-range obstruction of inferior vena cava. The biopsy proved to be hyperplastic nodules, also called large regenerative nodules (LRNs). Both benign regenerative nodules and hepatocellular carcinoma (HCC) appear in patients with BCC; however, published reports about the diagnosis and differential diagnosis are limited. The incidence of HCC in patients with BCS varies greatly depending on geography. This case illustrates that benign nodules can arise in BCS patients. We reviewed published reports and speculated that medical procedures leading to portal perfusion decrease may be associated with the development of these hyperplastic nodules. PMID- 26142944 TI - Limbic encephalitis associated with leucine-rich glioma-inactivated 1 antibodies. AB - We describe the case of a patient with confirmed limbic encephalitis associated with leucine-rich glioma-inactivated 1 (LGI1) antibodies. A 59-year-old man presented to the Department of Neurology with bizarre behavior, memory loss, cognitive impairment, visual hallucinations, and myoclonus and facio-brachial dystonic seizures. A brain magnetic resonance imaging (MRI) revealed no hippocampal lesions. Blood tests showed hyponatremia. An electroencephalogram showed disorganization and slowing of background activity. Antiepileptic drugs were ineffective. The patient exhibited considerable improvement following immunotherapy. The diagnosis of limbic encephalitis associated with LGI1 antibodies should be considered in patients with clinical manifestations mimicking psychiatric disorders and in cases of refractory epilepsy especially with faciobrachial dystonic seizures. There is frequently hyponatremia, and cerebral MRI may be normal. Full recovery can be expected with early diagnosis and prompt treatment. PMID- 26142945 TI - Acute esophageal necrosis (black esophagus) in a 40-year-old man. PMID- 26142946 TI - Discovery of a novel 2,3,11,11a-tetrahydro-1H-pyrazino[1,2-b]isoquinoline-1,4(6H) dione series promoting neurogenesis of human neural progenitor cells. AB - A novel neurogenic compound (1), discovered from a mouse neural progenitor cell (NPC) screen, showed profound neurogenic effect on human NPCs. Synthesis and SAR of this novel 2,3,11,11a-tetrahydro-1H-pyrazino[1,2-b]isoquinoline-1,4(6H)-dione series are described. Compound 20 is brain penetrable in rodents, and promotes neurogenesis in wild type mice, therefore it is a good tool molecule to study neurogenesis induction as a potential treatment for conditions associated with neurogenesis impairment diseases. PMID- 26142948 TI - Positioning the hip with respect to the COM: Consequences for leg operation. AB - In bipedal runners and hoppers the hip is not located at the center of mass in the sagittal projection. This displacement influences operation and energetics of the leg attached to the hip. To investigate this influence in a first step a simple conservative bouncing template is developed in which a heavy trunk is suspended to a massless spring at a pivot point above the center of mass. This model describes the orientation of the ground reaction forces observed in experiments on running birds. In a second step it is assumed that an effective telescope leg with its hip fixed to the trunk remote from the COM generates the same ground reaction forces as those predicted by the template. For this effective leg the influence of hip placement on leg operation and energetics is investigated. Placing the hip directly below, at, or above the pivot point results in high axial energy storage. Posterior placement increases axial losses and hip work whereas anterior placement would require axial work and absorption at the hip. Shifting the hip far posteriorly as observed in some birds can lead to the production of pure extension torques throughout the stance phase. It is proposed that the relative placement of the hip with respect to the center of mass is an important measure to modify effective leg operation with possible implications for balancing the trunk and the control of legged motion systems. PMID- 26142947 TI - Potent benzoazepinone gamma-secretase modulators with improved bioavailability. AB - The triazolyl amide gamma-secretase modulators are potent alternatives to the cinnamyl amides that have entered the clinic for the treatment of Alzheimer's disease. Herein we build on the lead benzoazepinones described in our prior communication with imidazomethoxyarene moiety alternatives that offer opportunities to fine tune physical properties as well as address hERG binding and PK. Both half-life and bioavailability were significantly improved, especially in dog, with robust brain Abeta42 lowering maintained in both transgenic mouse and rat. PMID- 26142949 TI - ["Made-to-measure cardiology", personalized cardiology for the patient!]. PMID- 26142950 TI - [Violence undergone by the general practitioners: Under-reporting of the attacks or of the infringements to their properties]. AB - INTRODUCTION: The main objective of this study was to estimate prevalence on the liberal general practitioners. The secondary objectives are to identify the possible brakes with the declaration in the monitoring observatory for security of the doctors as well as to determine if the feminization of the profession was associated with the situations violence. METHODS: A questionnaire in 5 parts was submitted by telephone to 146 drawn lots liberal general practitioners. It approached the undergone physical and verbal attacks, the infringements on the properties arisen during their career, and the proven feeling of insecurity. RESULTS: The rate of participation was 63% (93/146). In all 171 incidents were reported among which 96 physical and verbal attacks (56%), and 75 infringements on the properties (44%) without difference according to the sex. The main motive for the attacks was the refusal of prescription (44%). Practically, no concerned doctor made declaration for the monitoring observatory for the security of the doctors, for lack of interest for 5 of them or the ignorance of its existence for 10 on 32 practitioners having undergone an aggression after the creation of the monitoring observatory. CONCLUSION: We observed an under-reporting of the attacks or of the infringements on the properties by the doctors victims. Our study did not highlight difference between men and women. PMID- 26142951 TI - Screening Breast MRI in Patients Previously Treated for Breast Cancer: Diagnostic Yield for Cancer and Abnormal Interpretation Rate. AB - RATIONALE AND OBJECTIVES: To determine the cancer detection rate and abnormal interpretation rate of screening breast magnetic resonance imaging (MRI) in previously treated breast cancer patients. MATERIALS AND METHODS: Institutional review board-approved retrospective review of the breast MRI database from 2009 to 2011 identified a total of 3297 screening examinations. After excluding genetic mutation carriers, untested first-degree relatives of known mutation carriers, and patients with a history of chest irradiation, there were 1194 (36.2%) examinations in 691 patients previously treated for breast cancer. MRI reports were reviewed to determine MRI findings and breast imaging reporting and data system (BI-RADS) assessments. The longitudinal medical record was reviewed to determine patient demographics and outcomes of imaging surveillance and biopsy. RESULTS: Mean patient age at initial cancer diagnosis was 46.1 years, and mean patient age during the study interval was 52 years. Cancer detection rate was 10 per 1000 (1%; 95% confidence interval [CI], 0.5%-1.8%]; 12 of 1194 examinations). Overall 10.7% (128 of 1194) of examinations received an abnormal interpretation, including 5.4% (65 of 1194) BI-RADS 4 or 5 and 5.3% (63 of 1194) BI-RADS 3 assessments with a 9.4% positive predictive value (PPV1; 12 of 128 examinations) and a 17.9% PPV3 (12 malignancies per 67 biopsies). CONCLUSIONS: Screening breast MRI in women previously treated for breast cancer detected cancer in 1.0% of examinations, with a 10.7% abnormal interpretation rate, and a PPV for malignancy of 17.9%. PMID- 26142953 TI - Limbal melanocytes support limbal epithelial stem cells in 2D and 3D microenvironments. AB - Human limbal epithelial stem cells (LESCs) are essential for the maintenance of the corneal epithelium of the ocular surface. LESCs are located within limbal crypts between the palisades of Vogt in the limbus; the interface between the peripheral cornea and conjunctiva. The limbal crypts have been proposed as a LESC niche owing to their support of epithelial cells, which can form holoclone colonies in vitro. Closely associated with the limbal crypts is a concentrated population of melanocytes. The anatomical location and close proximity to putative LESC suggests that melanocytes might play a role in maintenance of these stem cells in the niche. The aim of this study was to assess the ability of human limbal melanocytes (hLM) to support the expansion of human limbal epithelial cells (LECs) in vitro as an indicator of functional cell-cell interaction. After observing that hLM co-localize with clusters of compact epithelial cells in the native limbal crypts, hLM were isolated from crypt-rich cadaveric limbal biopsies and used as feeders for the culture of LECs. Interestingly, LECs grown on mitotically active hLM were able to generate large epithelial colonies that contained small and compact cells with morphological stem cell characteristics. Immunocytochemistry revealed that LECs expanded on hLM were positive for the expression of the putative stem cell markers CK15, Bmi-1 and p63alpha and negative for the marker of terminal cell differentiation CK3. LECs and hLM were finally co-cultured on RAFT (real architecture for 3D tissue) collagen tissue equivalents. In 3D co-cultures, hLM promoted multi-layering of the epithelial sheet in which basal cells were maintained in an undifferentiated state. Taken together, these observations suggest melanocytes could play an important role in the maintenance of LESCs in the native human limbal stem cell niche. PMID- 26142952 TI - Optineurin: The autophagy connection. AB - Optineurin is a cytosolic protein encoded by the OPTN gene. Mutations of OPTN are associated with normal tension glaucoma and amyotrophic lateral sclerosis. Autophagy is an intracellular degradation system that delivers cytoplasmic components to the lysosomes. It plays a wide variety of physiological and pathophysiological roles. The optineurin protein is a selective autophagy receptor (or adaptor), containing an ubiquitin binding domain with the ability to bind polyubiquitinated cargoes and bring them to autophagosomes via its microtubule-associated protein 1 light chain 3-interacting domain. It is involved in xenophagy, mitophagy, aggrephagy, and tumor suppression. Optineurin can also mediate the removal of protein aggregates through an ubiquitin-independent mechanism. This protein in addition can induce autophagy upon overexpression or mutation. When overexpressed or mutated, the optineurin protein also serves as a substrate for autophagic degradation. In the present review, the multiple connections of optineurin to autophagy are highlighted. PMID- 26142954 TI - Protection of retinal function by sulforaphane following retinal ischemic injury. AB - Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. PMID- 26142955 TI - Prostaglandin induced changes in the tone of porcine retinal arterioles in vitro involve other factors than calcium activity in perivascular cells. AB - The cellular basis for the regulation of retinal blood flow is unknown, but recently a new type of perivascular cell (PVC) with pericyte characteristics was identified in the retinal arterial vascular wall located immediately external to the vascular smooth muscle cells. A possible involvement of this cell type in the regulation of retinal vascular tone might be elucidated by studying differences in the response after the addition of compounds stimulating respectively relaxation and contraction. The effects of PGE2 and PGF2alpha on vascular tone and calcium activity in PVCs in porcine retinal arterioles were studied in a confocal myograph after the addition of the ryanodine receptor blocker ryanodine, the L-type Ca(2+) channel blocker nifedipine, the non-specific cation channel blocker LOE908, the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) blocker CPA, and the inositol triphosphate receptor (IP3R) and transient receptor potential (TRP) ion channel blocker 2-APB. The Ca(2+) channel blockers nifedipine and LOE908 induced significant relaxation of retinal arterioles. After the addition of both PGE2 and PGF2alpha calcium activity in the PVCs was significantly reduced by both the SERCA inhibitor CPA and the IP3R antagonist 2-APB, but the changes in calcium activity were unrelated to the changes in tone induced by PGE2 and PGF2alpha. Changes in the tone of porcine retinal arterioles in vitro induced by PGE2 and PGF2alpha involve other factors than calcium activity in the perivascular cells. PMID- 26142956 TI - Reduction of amyloid-beta levels in mouse eye tissues by intra-vitreally delivered neprilysin. AB - Amyloid-beta (Abeta) is a group of aggregation-prone, 38- to 43-amino acid peptides generated in the eye and other organs. Numerous studies suggest that the excessive build-up of low-molecular-weight soluble oligomers of Abeta plays a role in the progression of Alzheimer's disease and other brain degenerative diseases. Recent studies raise the hypothesis that excessive Abeta levels may contribute also to certain retinal degenerative diseases. These findings, together with evidence that a major portion of Abeta is released as monomer into the extracellular space, raise the possibility that a technology enabling the enzymatic break-down of monomeric Abeta in the living eye under physiological conditions could prove useful for research on ocular Abeta physiology and, perhaps ultimately, for therapeutic applications. Neprilysin (NEP), an endopeptidase known to cleave Abeta monomer into inactive products, is a membrane associated protein. However, sNEP, a recombinant form of the NEP catalytic domain, is soluble in aqueous medium. With the aim of determining the Abeta cleaving activity of exogenous sNEP in the microenvironment of the intact eye, we analyzed the effect of intra-vitreally delivered sNEP on ocular Abeta levels in mice that exhibit readily measurable, aqueous buffer-extractable Abeta40 and Abeta42, two principal forms of Abeta. Anesthetized 10-month wild-type (C57BL/6J) and 2-3-month 5XFAD transgenic mice received intra-vitreal injections of sNEP (0.004-10 MUg) in one eye and were sacrificed at defined post-treatment times (30 min - 12 weeks). Eye tissues (combined lens, vitreous, retina, RPE and choroid) were homogenized in phosphate-buffered saline, and analyzed for Abeta40 and Abeta42 (ELISA) and for total protein (Bradford assay). The fellow, untreated eye of each mouse served as control, and concentrations of Abeta (pmol/g protein) in the treated eye were normalized to that of the untreated control eye. In C57BL/6J mice, as measured at 2 h after sNEP treatment, increasing amounts of injected sNEP yielded progressively greater reductions of Abeta40, ranging from 12% +/- 3% (mean +/- SEM; n = 3) with 4 ng sNEP to 85% +/- 13% (n = 5) with 10 MUg sNEP. At 4 ng sNEP the average Abeta40 reduction reached >70% by 24 h following treatment and remained near this level for about 8 weeks. In 5XFAD mice, 10 MUg sNEP produced an Abeta40 decrease of 99% +/- 1% (n = 4) and a substantial although smaller decrease in Abeta42 (42% +/- 36%; n = 4) within 24 h. Electroretinograms (ERGs) were recorded from eyes of C57BL/6J and 5XFAD mice at 9 days following treatment with 4 ng or 10 MUg sNEP, conditions that on average led, respectively, to an 82% and 91% Abeta40 reduction in C57BL/6J eyes, an 87% and 92% Abeta40 reduction in 5XFAD eyes, and a 23% and 52% Abeta42 reduction in 5XFAD eyes. In all cases, sNEP-treated eyes exhibited robust ERG responses, consistent with a general tolerance of the posterior eye tissues to the investigated conditions of sNEP treatment. The sNEP-mediated decrease of ocular Abeta levels reported here represents a possible approach for determining effects of Abeta reduction in normally functioning eyes and in models of retinal degenerative disease. PMID- 26142959 TI - Enhanced charge-carrier transfer by CdS and Ag2S quantum dots co-sensitization for TiO2 nanotube arrays. AB - Thioglycollic acid was employed as a molecular linker to prepare CdS and/or Ag2S quantum dots (QDs) for the co-sensitization of TiO2 nanotube arrays through the successive ionic layer adsorption and reaction (SILAR) method. The microstructure, chemical composition, and photoabsorption of the prepared samples were analyzed by using field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and UV-Vis diffuse reflectance spectroscopy (UV Vis DAS). The interfacial separation and transport of photoinduced charge carries were also examined by applying current-voltage characteristics (J-V), electrochemical impedance spectroscopy (EIS), transient open circuit potential plots, and Mott-Schottky techniques. The sizes of the CdS and Ag2S QDs were found to be 6 and 4 nm, respectively. The co-sensitized samples demonstrate significantly enhanced photo absorption, greatly reduced charge transfer resistance at the semiconductor interfaces, positive shift of the flat band, elongated electron lifetimes, and accelerated interfacial separation and transport of the photoinduced charge carriers. A critical operation sequence is to first carry out the deposition of the CdS QDs that are less mismatched with TiO2 crystal lattice, followed by the deposition of Ag2S QDs. The samples prepared in this manner presented the best optoelectronic characteristics with a short photocurrent density of 9.5 mA.cm(-2). This value is 7.6% higher than 8.83 mA.cm(-2) of the sample prepared by depositing the more mismatched Ag2S QDs followed by deposition of CdS. This value is 18.8% higher than 8 mA.cm(-2) of the Ag2S-only sensitized sample, and 22.6% higher than 7.75 mA.cm(-2) of the CdS-only sensitized sample. PMID- 26142957 TI - Inhibitory effects of PPARgamma ligands on TGF-beta1-induced CTGF expression in cat corneal fibroblasts. AB - Ligands of Peroxisome Proliferator Activated Receptor gamma (PPARgamma) possess strong anti-fibrotic properties in the cornea and several other body tissues. In the cornea, we recently showed this class of molecules to prevent stromal myofibroblast differentiation partially by blocking the actions of p38 mitogen activated protein kinase (MAPK). However, given the important role assigned to connective tissue growth factor (CTGF) in mediating corneal fibrosis, here we asked whether PPARgamma ligands also act by affecting transforming growth factor beta (TGF-beta) 1-induced expression of CTGF in cultured corneal fibroblasts. Corneal keratocytes were isolated from young, adult cats and early passage cells were exposed to TGF-beta1 with or without the PPARgamma ligands Rosiglitazone, Troglitazone and 15d-PGJ2. Western blots were used to assay levels of CTGF and alpha smooth muscle actin (alphaSMA), a marker of myofibroblast differentiation. CTGF siRNA demonstrated a critical role for CTGF in TGF-beta1-mediated myofibroblast differentiation, while exogenously applied CTGF potentiated the pro fibrogenic effects of TGF-beta1. TGF-beta1-mediated increases in CTGF and alphaSMA expression were strongly inhibited by all three PPARgamma ligands tested, and by a c-jun N-terminal kinase (JNK) inhibitor. However, while extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT) and p38 MAPK inhibitors also blocked TGF-beta1-induced alphaSMA induction, they did not dampen TGF-beta1-induced increases in levels of CTGF. Thus, we conclude that PPARgamma ligands block TGF-beta1-induced increases in CTGF levels in cat corneal fibroblasts. They appear to do this in addition to their anti-fibrotic effect on p38 MAPK, providing a second intracellular pathway by which PPARgamma ligands block alphaSMA induction. PMID- 26142958 TI - Apprehending ganglioside diversity: a comprehensive methodological approach. AB - Gangliosides (GGs) make a wide family of glycosphingolipids ubiquitously expressed in mammalian tissues and particularly abundant in the brain and nervous system. They exhibit a huge diversity due to structural variations in both their oligosaccharidic chain and ceramide moiety, which represent a real analytical challenge. Since their discovery in the 1940s, methods have persistently improved until the emergence of LC/MS, which offers a high level of specificity and sensitivity and is suitable with high-throughput profiling studies. We describe here a comprehensive approach relying on various techniques and aiming at fully characterizing GGs in biological samples. First, total GG content was determined by a biochemical assay. Second, GG class composition was assessed by high performance thin-layer chromatography followed by colorimetric revelation. Then, ceramide types of GG classes were identified, and their relative quantification was performed thanks to the development of a powerful and reliable LC/MS method. Finally, ceramides were structurally characterized, and minor and less common GG classes were identified using high-resolution MS. These methods were applied to the rat retina to provide an exhaustive description of its GG composition, giving the base for a better understanding of the precise roles of GGs in this tissue. PMID- 26142960 TI - Lesion morphological classification by OCT to predict therapeutic efficacy after balloon pulmonary angioplasty in CTEPH. PMID- 26142961 TI - Subarachnoid bleeding triggering Takotsubo syndrome. PMID- 26142962 TI - Impact of the "ACT NOW. SAVE A LIFE" public awareness campaign on the performance of a European STEMI network. PMID- 26142963 TI - Renal sympathetic denervation: A potential therapeutic approach for long QT syndrome. PMID- 26142964 TI - Coronary flow assessment in Takotsubo cardiomyopathy with TIMI frame count. PMID- 26142965 TI - Renin-angiotensin-aldosterone system genotype and serum BNP in a contemporary cohort of adults late after Fontan palliation. AB - BACKGROUND: Adults with single ventricle physiology palliated with a Fontan circulation experience high mortality due to circulatory failure. Renin angiotensin-aldosterone system (RAAS) genotype contributes to adverse cardiovascular outcomes in acquired heart failure. This study evaluated associations between RAAS genotype, ventricular mass and function in a contemporary cohort of adults with a Fontan circulation. METHODS: This single center prospective study included adults (n=106) seen after the Fontan operation (mean age 27+/-9years). Patients were genotyped for 5 pro-hypertrophic RAAS gene polymorphisms. Serum BNP, ventricular mass and function, and clinical events were compared between those with >=2 homozygous risk genotypes ("high-risk", n=31) versus those with <=1 homozygous risk genotypes ("low risk", n=75). RESULTS: "High-risk" genotype was associated with diastolic dysfunction and higher serum BNP levels. There was no association between RAAS genotype and either ventricular mass or systolic function. During a mean follow-up duration of 9.5+/-7.6years, late Fontan failure occurred in 20% (n=21) of patients, including 7 deaths. Serum BNP emerged as an independent predictor of late Fontan failure (HR 1.11 [CI 1.01 1.23] for each 50unit increase in BNP, p=0.04) and death alone (HR 1.25 [CI 1.07 1.47] for each 50unit increase in BNP, p=0.006). RAAS genotype was not associated with adverse clinical events. CONCLUSIONS: Fontan failure is common among adults with single ventricle physiology. RAAS genotype is not associated with increased ventricular mass but does appear to influence diastolic function late after the Fontan operation. Elevated BNP is an independent predictor of Fontan failure and mortality in adulthood. PMID- 26142966 TI - Kounis syndrome: Report of 3 cases. PMID- 26142967 TI - Balloon pulmonary angioplasty-related complications and therapeutic strategy in patients with chronic thromboembolic pulmonary hypertension. PMID- 26142968 TI - Is there a place for intra-aortic balloon counterpulsation support in acute right ventricular failure by pressure-overload? AB - BACKGROUND: Most therapeutic strategies for acute right ventricular failure (RVF) by pressure-overload are directed to improve cardiac output and coronary perfusion pressure by vasopressive agents. The eventual role of intra-aortic balloon counterpulsation (IABP) support remains questionable. This study investigates the contribution of IABP for acute RVF by pressure-overload, in comparison with phenylephrine (PE) and norepinephrine (NOR). METHODS: Acute RVF is induced by fixed pulmonary artery constriction in 6 pigs, pursuing a 50% reduction of cardiac output. Assessment of the treatment interventions included biventricular PV-loop analysis, and continuous measurement of aortic and right coronary artery flow. RESULTS: Restoration of baseline cardiac output was only observed by administration of NOR (Baseline=3.82+/-1.52ml/min - RVF=2.03+/ 0.59ml/min - IABP=2.45+/-0.62ml/min - PE=2.98+/-0.63ml/min - NOR=3.95+/ 0.73ml/min, p<0.001). NOR had most effect on biventricular contractility (PRSW slope-RV: IABP +24% - PE +59% - NOR +208%, p<0.001 and PRSW-slope-LV: IABP +36% - PE +53% - NOR +196%, p<0.001), heart rate acceleration (IABP +7% - PE +12% - NOR +51%, p<0.001), and RCA flow (IABP +31% - PE +58% - NOR +180%, p<0.001), concomitant to a higher increase of LV-to-RV pressure ratio (IABP: +7% versus 3%, PE: +36% versus +8%, NOR: +101% versus 42%). The hemodynamic contribution of IABP was limited, unless a modest improvement of LV compliance during PE and NOR infusion. CONCLUSION: In a model of acute pressure-overload RV failure, IABP appears to offer limited hemodynamic benefit. The administration of norepinephrine is most effective to correct systemic output and myocardial perfusion through adding an inotropic and chronotropic effect to systemic vasopression. PMID- 26142969 TI - Elevated glycated albumin and reduced endogenous secretory receptor for advanced glycation endproducts levels in serum predict major adverse cardio-cerebral events in patients with type 2 diabetes and stable coronary artery disease. AB - BACKGROUND AND AIM: Glycated albumin (GA) and the endogenous secretory receptor for advanced glycation endproducts (esRAGE) may modulate risk related to atherosclerosis. We tested the hypothesis that elevated GA and reduced esRAGE in serum are associated with adverse clinical outcomes in patients with type 2 diabetes and stable coronary artery disease (CAD). METHODS: We determined GA and esRAGE serum levels in 576 consecutive patients with type 2 diabetes and stable CAD undergoing sirolimus-eluting stent (SES)-PCI. The primary endpoint was the incidence of major adverse cardio-cerebral events (MACCE) including cardiac death, non-fatal myocardial infarction, and non-fatal stroke during a 2-year follow-up. The secondary endpoint was the occurrence of clinically driven repeat revascularization during a 2-year follow-up. The prognostic value of GA and esRAGE was determined with the Cox-proportional hazard model after adjustment for covariates. RESULTS: A total 40 patients (6.9%) experienced MACCE, and 108 (18.8%) patients underwent repeat coronary revascularization during the follow up. Serum GA (HR=1.22, 95% CI 1.16-1.28; HR=1.15, 95% CI 1.11-1.19, respectively; for both p<0.001) and esRAGE (HR=0.60, 95% CI 0.40-0.87; HR=0.75, 95% CI 0.61 0.92, respectively; for both p<0.01) levels remained independent predictors of the primary and secondary endpoints after adjustment for possible confounders. CONCLUSIONS: Serum GA and esRAGE are novel predictors of long-term clinical outcomes in patients with type 2 diabetes and stable CAD. Increased serum GA and decreased esRAGE are associated with a poor prognosis in such patients. PMID- 26142970 TI - My patient wants to perform strenuous endurance exercise. What's the right advice? AB - Prolonged strenuous endurance exercise (SEE) such as marathon running has recently been associated with potential deleterious cardiac effects, particularly increased risk of atrial fibrillation (AF). This topic is medically important due to the increasing number of participants in SEE events lasting several hours, including older people. The aim of this narrative review is to provide a summary of the evidence available on SEE and related issues such as cardiovascular mortality, AF, potential cardiac remodeling, cardiovascular events during exertion, or the need for pre-participation screening (with a special focus on beginners). This type of information can help physicians giving advice to their patients and the general public regarding safe SEE practice. PMID- 26142971 TI - Short-term exposure to ambient air pollution and coronary heart disease mortality in 8 Chinese cities. AB - BACKGROUND: Coronary heart disease (CHD) accounted for a large fraction of death globally. The association between air pollution and CHD has been reported, but evidence from highly-polluted regions was scarce. We aimed to estimate the acute effects of outdoor air pollution on daily CHD mortality in China. METHODS: We collected daily CHD deaths in 8 large Chinese cities from 1996 to 2008. We firstly obtained the city-specific effect estimates of air pollution using generalized additive models with quasi-Poisson regression, controlling for time trends, meteorological indicators and day of the week. The random-effect model in meta-analysis was used to pool the exposure-response relationships. RESULTS: We identified a total of 0.13 million CHD deaths. On average, an increase of 10MUg/m(3) in 2-day moving average concentrations of particulate matter<=10MUm in aerodynamic diameter (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) was significantly associated with increases of 0.36% [95% confidence intervals (CIs): 0.12%, 0.61%], 0.86% (95% CIs: 0.30%,1.41%) and 1.30% (95% CIs: 0.45%, 2.14%) in daily CHD mortality over the 8 Chinese cities, respectively. The pooled exposure response curves were almost linear and no apparent thresholds were identified. The effects were more pronounced in cities with lower levels of air pollution. The effects of PM10 and NO2 were more robust than SO2. CONCLUSION: Our findings contributed to the very limited evidence regarding the hazardous effects of ambient air pollution on CHD mortality in highly-polluted regions such as China. PMID- 26142972 TI - Uric acid is an independent predictor of cardiovascular events in post-menopausal women. AB - BACKGROUND: Uric acid (UA) is a risk factor for cardiovascular (CV) disease. In post-menopause UA levels are increased and strongly associated with subclinical organ damage. We investigated the prognostic significance of UA levels in predicting CV morbidity and mortality in post-menopausal women. METHODS: We considered 645 post-menopausal outpatients not taking hormone replacement therapy or any drugs interfering with UA levels. We evaluated major adverse cardiovascular events (MACE) as primary endpoint, with coronary, stroke or total events as secondary endpoint. Survival curves for tertiles of UA were obtained by using the Kaplan-Meier and Mantel methods. Effect of prognostic factors on survival was evaluated by multivariable Cox regression model, considering P<0.05 as statistically significant. RESULTS: During a mean (SD) follow-up at 72.5 (23.5) months, there were 90 new CV events (2.31%): 62 coronary and 28 cerebrovascular events. The rate of nonfatal CV events (3.15% versus 2.03% and 1.52%, P=0.009) as well as that of MACE (3.23% versus 2.11% and 1.59%, P=0.011) were significantly higher in the third tertile than in the other two groups. Interestingly, cerebrovascular (1.15% versus 0.62% and 0.30%, P=0.027) but not coronary events were significantly different among the three groups. In the Cox regression model, UA was independently and strongly associated with the incident risk of MACE (HR=1.248, P=0.001), cerebrovascular (HR=1.657, P<0.0001) and total events (HR=1.391, P<0.0001). CONCLUSIONS: In post-menopause, independently of other CV risk factors and menopause duration, UA levels are associated with increased risk of death and MACE, in particular cerebrovascular but not coronary events. PMID- 26142973 TI - Role of red blood cell distribution width in predicting contrast induced nephropathy in patients with stable angina pectoris undergoing percutaneous coronary intervention. PMID- 26142974 TI - Contrast media and thrombosis. PMID- 26142975 TI - Interosseous artery collaterals and their support to ulno-palmar arch: A case report and a review of the literature. PMID- 26142976 TI - An unusual cause of dynamic left ventricular outflow obstruction: An unusual case of dynamic LVOTO. PMID- 26142977 TI - Accessory papillary muscles and papillary muscle hypertrophy are associated with sudden cardiac arrest of unknown cause. AB - BACKGROUND: The present study was performed for elucidating the associations between the morphology of the papillary muscles (PMs) and sudden cardiac arrest (SCA). METHODS: We retrospectively reviewed history, laboratory data, electrocardiography, echocardiography, coronary angiography, and cardiac CT/MRI for 190 patients with SCA. The prevalence of accessory PMs and PM hypertrophy in patients with SCA of unknown cause was compared with that in patients with SCA of known causes and 98 age- and sex-matched patients without SCA. An accessory PM was defined as a PM with origins separated from the anterolateral and posteromedial PMs, or a PM that branched into two or three bellies at the base of the anterolateral or posteromedial PM. PM hypertrophy was defined as at least one of the two PMs having a diameter of >=1.1cm. RESULTS: In 49 patients (age 49.9+/ 15.9years; 38 men) the cause of SCA was unknown, whereas 141 (age 54.2+/ 16.6years; 121 men) had a known cause. The prevalence of accessory PMs was significantly higher in the unknown-cause group than in the known-cause group (24.5% and 7.8%, respectively; p=0.002) or the no-SCA group (7.1%, p=0.003). The same was true for PM hypertrophy (unknown-cause 12.2%, known-cause 2.1%, p=0.010; no SCA group 1.0%, p=0.006). By logistic regression, accessory PM and PM hypertrophy were independently associated with sudden cardiac arrest of unknown cause. CONCLUSIONS: An accessory PM and PM hypertrophy are associated with SCA of unknown cause. PMID- 26142978 TI - Hs-cTnT levels in professional soccer players throughout a season: No evidence of sustained cardiac damage. PMID- 26142979 TI - A hypothesis: Glucagon-like peptide-1 may play a protective role in diabetic cardiomyopathy. PMID- 26142980 TI - An uncommon case of dyspnea with unilateral laryngeal paralysis in acromegaly. AB - A 61-year-old man with obstructive sleep apnea syndrome and normal BMI complained of dyspnea. Nasofibroscopy revealed a global and major oedema of the glottis and supraglottis and also a paralysis of the left vocal fold. CT-scan pointed out a spontaneous hyperdensity of the left arytenoid cartilage. A tracheostomy was performed. Clinical examination revealed large hands and macroglossy with high IGF1 rate. MRI confirmed a supracentimetric pituitary adenoma. To our knowledge, this is the first description of a case of acute respiratory distress due to unilateral larynx paralysis leading to acromegaly diagnosis. This is due to submucosal hypertrophy and vocal cord immobility. PMID- 26142981 TI - Realization problem of multi-layer cellular neural networks. AB - This paper investigates whether the output space of a multi-layer cellular neural network can be realized via a single layer cellular neural network in the sense of the existence of finite-to-one map from one output space to the other. Whenever such realization exists, the phenomena exhibited in the output space of the revealed single layer cellular neural network is at most a constant multiple of the phenomena exhibited in the output space of the original multi-layer cellular neural network. Meanwhile, the computation complexity of a single layer system is much less than the complexity of a multi-layer system. Namely, one can trade the precision of the results for the execution time. We remark that a routine extension of the proposed methodology in this paper can be applied to the substitution of hidden spaces although the detailed illustration is omitted. PMID- 26142982 TI - Towards unified characterization of cooperation mechanisms: Comment on "Universal scaling for the dilemma strength in evolutionary games" by Z. Wang et al. PMID- 26142983 TI - Adaptive neural network control of unknown nonlinear affine systems with input deadzone and output constraint. AB - In this paper, we aim to solve the control problem of nonlinear affine systems, under the condition of the input deadzone and output constraint with the external unknown disturbance. To eliminate the effects of the input deadzone, a Radial Basis Function Neural Network (RBFNN) is introduced to compensate for the negative impact of input deadzone. Meanwhile, we design a barrier Lyapunov function to ensure that the output parameters are restricted. In support of the barrier Lyapunov method, we build an adaptive neural network controller based on state feedback and output feedback methods. The stability of the closed-loop system is proven via the Lyapunov method and the performance of the expected effects is verified in simulation. PMID- 26142984 TI - Hybrid method for designing digital FIR filters based on fractional derivative constraints. AB - In this manuscript, a hybrid approach based on Lagrange multiplier method and cuckoo search (CS) optimization technique is proposed for the design of linear phase finite impulse response (FIR) filters using fractional derivative constraints. In the proposed method, FIR filter is designed by optimizing the integral squares in passband and stopband from ideal response such that the fractional derivatives of designed filter response become zero at a given frequency point. Lagrange multiplier method is exploited for finding the optimized filter coefficients. Optimal value of fractional derivative constraints for optimized filter coefficients are determined by minimizing the objective function constructed using a sum of maximum passband ripple and maximum stopband ripple in frequency domain using CS algorithm. Performance of the proposed method is evaluated by passband error (phi(p)), stopband error (phi(s)), stopband attenuation (A(s)), maximum passband ripple (MPR), maximum stopband ripple (MSR) and CPU time. A comparative study of the performance of particle swarm optimization (PSO) and artificial bee colony (ABC) for designing FIR filters using the proposed method is also made. PMID- 26142985 TI - Breaking Down the Door Between EMS and the Emergency Department. PMID- 26142986 TI - What's in a Name? PMID- 26142987 TI - Caring for Inpatient Boarders in the Emergency Department. PMID- 26142988 TI - Response. PMID- 26142989 TI - AONE and ENA Develop Guiding Principles on Mitigating Violence in the Workplace. PMID- 26142991 TI - Clinical Research: The Importance of Meta-Analysis and Systematic Reviews in Determining Appropriate Practice Changes. PMID- 26142992 TI - Critical Thinking at Triage: Ask the Question! PMID- 26142993 TI - Intraosseous and Endotracheal Tube Medications. PMID- 26142994 TI - Characterization of a novel cometabolic degradation carbazole pathway by a phenol cultivated Arthrobacter sp. W1. AB - Arthrobacter sp. W1 was used to characterize the pathways involved in cometabolic degradation of carbazole (CA) with phenol as the primary substrate. To clarify the upper pathway of cometabolic degradation CA, Escherichia coli strain BL21 expressing phenol hydroxylase from strain W1 (PHIND) was investigated to degrade CA. Firstly, CA was initially monohydroxylated at C-2 and C-4 positions to produce 2- and 4-hydroxycarbazole, followed by successively hydroxylated to the corresponding 1,2- and 3,4-dihydroxycarbazole, of which 3,4-dihydroxycarbazole was unequivocally identified for the first time. To characterize the downstream cometabolic degradation CA pathway, purified 3,4-dihydroxycarbazole was used as the substrate for phenol-grown W1, and a series of novel indole derivatives were identified. These results suggested that a novel pathway of CA catabolism was employed by strain W1 via a successive hydroxylation and meta-cleavage pathway. These findings provide new insights into the cometabolic degradation CA process and have potential applications in biotechnology and bioremediation. PMID- 26142995 TI - Mechanism of improved cellulosic bio-ethanol production from alfalfa stems via ambient-temperature acid pretreatment. AB - Model compounds and recalcitrant biomass were studied to elucidate the mechanism of ambient-temperature acid pretreatment of cellulosic biomass for bio-ethanol production. Pure cellulose, a pure hemicellulose and alfalfa stems were pretreated with sulfuric acid under ambient temperature with varied acid loading and time. Changes in water-soluble carbohydrates (WSCs) and chemical components of substrates were determined, and ethanol production via simultaneous saccharification and fermentation (SSF) was studied. The results showed significant amount of WSCs formed, and the WSCs increased with increasing acid loading and pretreatment time. The ethanol yields from pure cellulose were primarily affected by the added ash. Acid loading showed significant positive effect on ethanol production from alfalfa stems, whereas pretreatment time showed much weaker positive effect. However, non-significant amounts of WSCs were removed by washing of dried substrates. It was hypothesized to be because the WSCs adsorbed onto bulk substrates during the freeze-drying step, as supported by experimental results. PMID- 26142996 TI - Biohydrogen production by co-fermentation of crude glycerol and apple pomace hydrolysate using co-culture of Enterobacter aerogenes and Clostridium butyricum. AB - Co-substrate utilization of various wastes with complementary characteristics can provide a complete medium for higher hydrogen production. This study evaluated potential of apple pomace hydrolysate (APH) co-fermented with crude glycerol (CG) for increased H2 production and decreased by-products formation. The central composite design (CCD) along with response surface methodology (RSM) was used as tool for optimization and 15 g/L of CG, 5 g/L of APH and 15% (v/v) inoculum were found to be optimum to produce as high as 26.07 +/- 1.57 mmol H2/L of medium. The p-value of 0.0017 indicated that APH at lower concentration had a significant effect on H2 production. By using CG as sole carbon source, reductive pathway of glycerol metabolism was favored with 19.46 mmol H2/L. However, with APH, oxidative pathway was favored with higher H2 production (26.07 +/- 1.57 mmol/L) and decrease in reduced by-products (1,3-propanediol and ethanol) formation. APH inclusion enhanced H2 production, and decreased substrate inhibition. PMID- 26142997 TI - Elimination patterns of worldwide used sulfonamides and tetracyclines during anaerobic fermentation. AB - Antibiotics such as sulfonamides and tetracyclines are frequently used in veterinary medicine. Due to incomplete absorption in the animal gut and/or unmetabolized excretion, the substances can enter the environment by using manure as soil fertilizer. The anaerobic fermentation process of biogas plants is discussed as potential sink for antibiotic compounds. However, negative impacts of antibiotics on the fermentation process are suspected. The elimination of sulfadiazine, sulfamethazine, tetracycline and chlortetracycline in semi continuous lab-scale fermenters was investigated. Both biogas production and methane yield were not negatively affected by concentrations up to 38 mg per kg for sulfonamides and 7 mg per kg for tetracyclines. All substances were partly eliminated with elimination rates between 14% and 89%. Both matrix and structure of the target molecule influenced the elimination rate. Chlortetracycline was mainly transformed into iso-chlortetracycline. In all other cases, the elimination pathways remained undiscovered; however, sorption processes seem to have a negligible impact. PMID- 26142999 TI - Enhancement of enzymatic saccharification of corn stover with sequential Fenton pretreatment and dilute NaOH extraction. AB - In this study, an effective method by the sequential Fenton pretreatment and dilute NaOH extraction (FT-AE) was chosen for pretreating corn stover. Before dilute NaOH (0.75 wt%) extraction at 90 degrees C for 1h, Fenton reagent (0.95 g/L of FeSO4 and 29.8 g/L of H2O2) was employed to pretreat CS at a solid/liquid ratio of 1/20 (w/w) at 35 degrees C for 30 min. The changes in the cellulose structural characteristics (porosity, morphology, and crystallinity) of the pretreated solid residue were correlated with the enhancement of enzymatic saccharification. After being enzymatically hydrolyzed for 72 h, the reducing sugars and glucose from the hydrolysis of 60 g/L FT-AE-CS pretreated could be obtained at 40.96 and 23.61 g/L, respectively. Finally, the recovered hydrolyzates containing glucose had no inhibitory effects on the ethanol fermenting microorganism. In conclusion, the sequential Fenton pretreatment and dilute NaOH extraction has high potential application in future. PMID- 26142998 TI - Bicarbonate supplementation enhanced biofuel production potential as well as nutritional stress mitigation in the microalgae Scenedesmus sp. CCNM 1077. AB - The aim of the present study was to find out the optimum sodium bicarbonate concentration to produce higher biomass with higher lipid and carbohydrate contents in microalgae Scenedesmus sp. CCNM 1077. The role of bicarbonate supplementation under different nutritional starvation conditions was also evaluated. The results clearly indicate that 0.6 g/L sodium bicarbonate was optimum concentration resulting in 20.91% total lipid and 25.56% carbohydrate along with 23% increase in biomass production compared to normal growth condition. Addition of sodium bicarbonate increased the activity of nutrient assimilatory enzymes, biomass, lipid and carbohydrate contents under different nutritional starvation conditions. Nitrogen starvation with bicarbonate supplementation resulted in 54.03% carbohydrate and 34.44% total lipid content in microalgae Scenedesmus sp. CCNM 1077. These findings show application of bicarbonate grown microalgae Scenedesmus sp. CCNM 1077 as a promising feedstock for biodiesel and bioethanol production. PMID- 26143000 TI - Efficient hydrolysis of corncob residue through cellulolytic enzymes from Trichoderma strain G26 and L-lactic acid preparation with the hydrolysate. AB - To prepare fermentable hydrolysate from corncob residue (CCR), Trichoderma strain G26 was cultured on medium containing CCR for production of cellulolytic enzymes through solid-state fermentation (SSF), resulting in 71.3 IU/g (FPA), 136.2 IU/g (CMCase), 85.1 IU/g (beta-glucosidase) and 11,344 IU/g (xylanase), respectively. Through a three-stage saccharification strategy, CCR was hydrolyzed by the enzymatic solution (6.5 FPU/ml) into fermentable hydrolysate containing 60.1g/l glucose (81.2% cellulose was converted at solid loading of 12.5%), 21.4% higher than that by the one-stage method. And then the hydrolysate was used to produce L lactic acid by a previous screened strain Bacillus coagulans ZX25 in the submerged fermentation. 52.0 g/l L-lactic acid was obtained after fermentation for 44 h, with 86.5% glucose being converted to L-lactic acid. The results indicate that the strains and the hydrolysis strategy are promising for commercial production of L-lactic acid from CCR and other biomass. PMID- 26143001 TI - Influence of two different alcohols in the esterification of fatty acids over layered zinc stearate/palmitate. AB - In this work, esterification of fatty acids (oleic, linoleic and stearic acid) with a commercial zinc carboxylate (a layered compound formed by simultaneous intercalation of stearate and palmitate anions) was performed. Kinetic modeling using a quasi-homogeneous approach successfully fitted experimental data at different molar ratio of fatty acids/alcohols (1-butanol and 1-hexanol) and temperature. An apparent first-order reaction related to all reactants was found and activation energy of 66 kJ/mol was reported. The catalyst showed to be unique, as it can be easily recovered like a heterogeneous catalysts behaving like ionic liquids. In addition, this catalyst demonstrated a peculiar behavior, because higher reactivity was observed with the increase in the alcohols chain length compared to the authors' previous work using ethanol. PMID- 26143002 TI - Xylose production from corn stover biomass by steam explosion combined with enzymatic digestibility. AB - A novel conversion process using steam explosion combined with enzymatic digestibility was exploited to increase sugar yield. Results showed that glucan and xylan recovery decreased with the increase of holding temperature and residence time in SE, respectively, while glucan and xylan conversion exhibited an opposite trend. The optimal conditions of steam explosion were 160 degrees C and 48 min, under which glucan and xylan recovery was 93.4% and 71.6%, respectively. Glucan and xylan conversion at 18% solid loading by periodic peristalsis increased by 3.4-5.8% and 4.5-6.2%, respectively, compared with that by water baths shaker. In the whole process, glucose, xylose and total sugar yield reached to 77.3%, 62.8% and 72.3%, respectively. The yield of hydroxymethyl furfural, furfural and lignin-derived products was 6.3 * 10(-2), 7.5 * 10(-2) and less than 3.7 * 10(-2) g/100 g feedstock, respectively. This novel conversion process increased sugar recovery, reduced degradation products formation, improved digestibility efficiency, and hence increased sugar yield. PMID- 26143003 TI - Application of ethylene diamine tetra acetic acid degrading bacterium Burkholderia cepacia on biotreatment process. AB - Ethylene diamine tetra acetic acid (EDTA), the effluent of secondary biotreatment units, can be properly biodegraded by Burkholderia cepacia. Through batch degradation of EDTA, the raw wastewater of EDTA was controlled at 50 mg/L, and then nutrients was added in diluted wastewater to cultivate activated sludge, which the ratio of composition is depicted as "COD:N:P:Fe = 100:5:1:0.5". After 27 days, the removal efficiency of Fe-EDTA and COD was 100% and 92.0%, correspondingly. At the continuous process, the raw wastewater of EDTA was dictated at 166 mg/L before adding nutrients to cultivate activated sludge, in which the ratio of composition did also follow with batch process. After 22 days, the removal efficiency of Fe-EDTA and COD for experimental group was 71.46% and 62.58%, correspondingly. The results showed that the batch process was more suited for EDTA biodegradation. PMID- 26143004 TI - Integrated process of two stage cultivation of Nannochloropsis sp. for nutraceutically valuable eicosapentaenoic acid along with biodiesel. AB - The marine eustigmatophyte Nannochloropsis is one of the potential producers of eicosapentaenoic acid (EPA), a valued nutraceutical. Nannochloropsis sp. was cultivated under photoautotrophic condition utilizing CO2 in a two phase cultivation process in order to enhance the eicosapentaenoic acid (EPA) productivity. It was cultivated in a photobioreactor up to late log phase for cell growth (phase I). Then, the culture was harvested and confronted to relatively low temperature (10 degrees C) and low light (30 MUmol photons m(-2) s(-1)) in both photobioreactor and Erlenmeyer flask (phase II), thus augmenting EPA% by 3.4 fold. Lower temperature with low light favored the synthesis of EPA although, biomass productivity, lipid content and lipid productivity were slightly decreased relative to phase I. The total lipids extracted from Nannochloropsis sp. fractionated into neutral lipids (NLs), glycolipids (GLs) and phospholipids (PLs) and a major proportion of EPA was found in phospholipids. Results suggested that low temperature and low light may ameliorate partitioning towards EPA in phospholipids. PMID- 26143005 TI - Distribution of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) in different stages of gestation sows: HP-PRRSV distribution in gestation sows. AB - Highly pathogenic PRRSV (HP-PRRSV) emerged in China in 2006 and caused severe reproductive losses, particularly in late-term sows. To determine whether these reproductive failures were related to the susceptibility of late-term sows to HP PRRV, 60- and 90-days of gestation sows were infected with HP-PRRSV isolate TA-12 (GenBank accession HQ417620). A monoclonal antibody specific to the C-terminal of the nucleocapsid protein was used to evaluate viral distribution by IHC. This showed that HP-PRRSV had a similar distribution in both sets of sows. However, HP PRRSV infection led to dramatically decreased serum levels of luteinizing hormone (LH) and 17-beta-estradiol (E2) in late-term sows, while only E2 was decreased in the 60-day sows. These results indicate that HP-PRRSV-induced reproductive failure is more likely due to reproductive hormone level imbalances rather than tissue tropism differences. PMID- 26143006 TI - Detection and quantification of bovine signal joint T-cell receptor excision circles. AB - A signal joint (sj) T-cell receptor excision circle (TREC) is produced by T-cell receptor (TCR) gene rearrangements during alphabeta T-cell maturation in the thymus. sjTREC have been studied as a marker of thymic function in several spices. We designed specific primers for deltarec-psiJalpha sj region to identify the location of the bovine sjTREC region and determined the nucleotide sequence of the PCR product. The obtained sequences were subjected to a BLAST search, which identified a matching region. This matching region contained TCR delta genes and was identified on bovine chromosome 10. We also confirmed the polymorphism of the sj region by sequencing of 10 PCR products, and observed irregular insertion of bases in the deltarec-psiJalpha recombination signal sequence. We then developed a quantitative PCR (QPCR) assay for evaluation of sjTRECs level in order to evaluate bovine thymic function for application in the veterinary clinic. This QPCR assay specifically amplified the sj region of bovine sjTREC and could detected 10(1)-10(7) copy numbers of sjTRECs. Using this assay we found that the number of sjTRECs in peripheral blood mononuclear cells was less than 10% that of the thymus. PMID- 26143007 TI - Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos. AB - Epigenetic mechanisms play critical roles in oogenesis and early embryo development in mammals. One of these epigenetic mechanisms, DNA methylation is accomplished through the activities of DNA methyltransferases (DNMTs), which are responsible for adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinuclotide sites. Five DNMT enzymes have been identified in mammals including DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L. They function in two different methylation processes: maintenance and de novo. For maintenance methylation, DNMT1 preferentially transfers methyl groups to the hemi-methylated DNA strands following DNA replication. However, for de novo methylation activities both DNMT3A and DNMT3B function in the methylation of the unmodified cytosine residues. Although DNMT3L indirectly contributes to de novo methylation process, DNMT2 enables the methylation of the cytosine 38 in the anticodon loop of aspartic acid transfer RNA and does not methylate DNA. In this review article, we have evaluated and discussed the existing published studies to characterize the spatial and temporal expression patterns of the DNMTs in mouse, bovine and human oocytes and early embryos. We have also reviewed the effects of in vitro culture conditions (serum abundance and glucose concentration), aging, superovulation, vitrification, and somatic cell nuclear transfer technology on the dynamics of DNMTs. PMID- 26143009 TI - Organellar non-coding RNAs: emerging regulation mechanisms. AB - Originally focused on the nuclear and cytosolic compartments, the concept of regulation driven by non-coding RNAs (ncRNAs) is extending to mitochondria and chloroplasts. These organelles have distinct genetic systems that need coordination with cellular demands. In mammals, nuclear-encoded microRNAs were found associated with the mitochondria. Some of these contribute to the regulation of mitochondrial transcription and translation. Others were proposed to be stored in the organelles and to be released for regulation of nuclear transcripts. Further ncRNAs of various sizes derive from the mitochondrial genome and it was speculated that organelles host antisense or RNA interference pathways. Long ncRNAs mapping to the mitochondrial DNA seem to operate in the nucleus. Altogether, the origin and trafficking of ncRNAs categorized as mitochondrial in mammals raise questions far beyond the current knowledge. In protozoa, hundreds of guide RNAs specify editing events needed to generate functional messenger RNAs. Only few ncRNAs have been reported in plant mitochondria, but editing sites were revealed in non-coding regions of the organellar genome, suggesting that the corresponding transcripts have a function. Conversely, numerous ncRNA candidates were identified in chloroplasts, essentially mapping to the plastid genome. A synthetic view of the data with their functional implications is given here. PMID- 26143008 TI - Cooperativity, allostery and synergism in ligand binding to riboswitches. AB - Recent progress in identification and characterization of novel types of non coding RNAs has proven that RNAs carry out a variety of cellular functions ranging from scaffolding to gene expression control. In both prokaryotic and eukaryotic cells, several classes of non-coding RNAs control expression of dozens of genes in response to specific cues. One of the most interesting and outstanding questions in the RNA field is whether regulatory RNAs are capable of employing basic biological concepts, such as allostery and cooperativity, previously attributed to the function of proteins. Aside from regulatory RNAs that form complementary base pairing with their nucleic acid targets, several RNA classes modulate gene expression via molecular mechanisms which can be paralleled to protein-mediated regulation. Among these RNAs are riboswitches, metabolite sensing non-coding regulatory elements that adopt intrinsic three-dimensional structures and specifically bind various small molecule ligands. These characteristics of riboswitches make them well-suited for complex regulatory responses observed in allosteric and cooperative protein systems. Here we present an overview of the biochemical, genetic, and structural studies of riboswitches with a major focus on complex regulatory mechanisms and biological principles utilized by riboswitches for such genetic modulation. PMID- 26143010 TI - Using the triage twelve-lead electrocardiogram to differentiate between Takotsubo cardiomyopathy and acute anterior ST-elevation myocardial infarction. PMID- 26143011 TI - The antinociceptive effects of the tetracyclic triterpene euphol in inflammatory and neuropathic pain models: The potential role of PKCepsilon. AB - Evidences suggest protein kinase C epsilon (PKCepsilon) activation is involved in both inflammatory and neuropathic pains. We have previously shown that tetracyclic triterpene euphol produces antinociception in different models of persistent pain, an action associated with its anti-inflammatory properties. Among these properties are the cannabinoid system activation and different PKC isozymes modulation. Herein, we sought to explore the potential role of PKCepsilon modulation on euphol antinociceptive effect, in inflammatory and neuropathic pain models, in rodents. Also, we investigated further mechanisms associated with euphol effects. Oral treatment with euphol (30 mg/kg) prevented the putative effect of PGE2-induced acute and persistent mechanical hypersensitivity in mice and rats, respectively. In the PGE2-induced acute mechanical hypersensitivity euphol promoted an inhibitory effect similar to a PKCepsilon inhibitor peptide. Likewise, in rats it prevented the mechanical hypersensitivity induced by a PKCepsilon activator. Conversely, euphol effectiveness was not observed in a cAMP/PKA-induced mechanical hypersensitivity in mice. Single (1h prior) or repeated (twice daily during 3 or 13 days) treatments with euphol ameliorated painful peripheral neuropathy induced by paclitaxel and also the mechanical hypersensitivity induced by B16F10 melanoma cells injection, in mice. Additionally, in both inflammatory and neuropathic pain models, euphol consistently prevented PKCepsilon up-regulation, as well as, inhibited the up-regulation of PKCepsilon-activated intracellular pathways; namely nuclear factor-kappaB (NF-kappaB), cyclic AMP response element binding protein (CREB) and cyclo-oxygenase-2 (COX-2). The present results suggest the antinociceptive effect on persistent pain caused by euphol is likely dependent on the inhibition of pro-inflammatory mediators modulated by PKCepsilon. PMID- 26143013 TI - Interaction between hypertension and cerebral hypoperfusion in the development of cognitive dysfunction and white matter pathology in rats. AB - Hypertension is the most significant modifiable risk factor for vascular cognitive impairment. However, influence of hypertension on the development of ischemic white matter injury and cognitive dysfunction is not fully understood. We compared cognitive functions and neuropathological outcomes of chronic cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAO) between normotensive rats (NRs) and spontaneously hypertensive rats (SHRs). SHRs developed earlier and more severe deficits in spatial memory performance than NRs following BCCAO. Although no significant changes in the gross structure of myelinated white matter or oligodendrocyte number were noted, BCCAO resulted in subtle myelin degeneration and paranodal structural alterations at the nodes of Ranvier, regardless of hypertension. Disruption of the blood brain barrier (BBB) was predominantly observed in the white matter of SHRs following BCCAO, implying a role of hypertension in BBB dysfunction in chronic cerebral hypoperfusion. In chronic cerebral ischemia, long-standing hypertension may aggravate impairment of BBB integrity, and the leaky BBB may in turn exacerbate dysfunction in the white matter leading to worsening of spatial cognitive performance. PMID- 26143012 TI - Disrupted sleep-wake regulation in type 1 equilibrative nucleoside transporter knockout mice. AB - The type 1 equilibrative nucleoside transporter (ENT1) is implicated in regulating levels of extracellular adenosine ([AD]ex). In the basal forebrain (BF) levels of [AD]ex increase during wakefulness and closely correspond to the increases in the electroencephalogram (EEG) delta (0.75-4.5Hz) activity (NRdelta) during subsequent non-rapid eye movement sleep (NREMS). Thus in the BF, [AD]ex serves as a biochemical marker of sleep homeostasis. Waking EEG activity in theta range (5-9Hz, Wtheta) is also described as a marker of sleep homeostasis. An hour by-hour temporal relationship between the Wtheta and NRdelta is unclear. In this study we examined the relationship between these EEG markers of sleep homeostasis during spontaneous sleep-wakefulness and during sleep deprivation (SD) and recovery sleep in the ENT1 gene knockout (ENT1KO) mouse. We observed that baseline NREMS amount was decreased during the light period in ENT1KO mice, accompanied by a weak correlation between Wtheta of each hour and NRdelta of its subsequent hour when compared to their wild-type (WT) littermates. Perfusion of low dose of adenosine into BF not only strengthened the Wtheta-NRdelta relationship, but also increased NREMS to match with the WT littermates suggesting decreased [AD]ex in ENT1KO mice. However, the SD-induced [AD]ex increase in the BF and the linear correlation between the EEG markers of sleep homeostasis were unaffected in ENT1KO mice suggesting that during SD, sources other than ENT1 contribute to increase in [AD]ex. Our data provide evidence for a differential regulation of wakefulness-associated [AD]ex during spontaneous vs prolonged waking. PMID- 26143014 TI - Neural evidence that suspense narrows attentional focus. AB - The scope of visual attention changes dynamically over time. Although previous research has reported conditions that suppress peripheral visual processing, no prior work has investigated how attention changes in response to the variable emotional content of audiovisual narratives. We used fMRI to test for the suppression of spatially peripheral stimuli and enhancement of narrative-relevant central stimuli at moments when suspense increased in narrative film excerpts. Participants viewed films presented at fixation, while flashing checkerboards appeared in the periphery. Analyses revealed that increasing narrative suspense caused reduced activity in peripheral visual processing regions in the anterior calcarine sulcus and in default mode network nodes. Concurrently, activity increased in central visual processing regions and in frontal and parietal regions recruited for attention and dynamic visual processing. These results provide evidence, using naturalistic stimuli, of dynamic spatial tuning of attention in early visual processing areas due to narrative context. PMID- 26143015 TI - Region-specific associations between sex, social status, and oxytocin receptor density in the brains of eusocial rodents. AB - Naturally occurring variations in neuropeptide receptor distributions in the brain contribute to numerous mammalian social behaviors. In naked mole-rats, which live in large social groups and exhibit remarkable reproductive skew, colony-related social behaviors vary with reproductive status. Here we examined whether variation in social status is associated with variations in the location and/or density of oxytocin binding in this species. Autoradiography was performed to assess forebrain oxytocin receptor (OTR) densities in breeding and non breeding naked mole-rats of both sexes. Overall, males exhibited higher OTR binding in the medial amygdala in comparison to females. While there were no main effects of reproductive status in any region, a sex difference in OTR binding in the nucleus accumbens was mediated by status. Specifically, breeding males tended to have more OTR binding than breeding females in the nucleus accumbens, while no sex difference was observed in subordinates. These effects suggest that oxytocin may act in a sex- and region-specific way that corresponds to reproductive status and associated social behaviors. PMID- 26143016 TI - Adjusting the Eneli et al. Feeding Dynamic Intervention to make it consistent with Satter feeding and eating models. PMID- 26143017 TI - Penicillin allergy label persists despite negative testing. PMID- 26143018 TI - Critique on the quantitative nature of IgE antibody measurements. PMID- 26143019 TI - Oral Phenylephrine HCl for Nasal Congestion in Seasonal Allergic Rhinitis: A Randomized, Open-label, Placebo-controlled Study. AB - BACKGROUND: Phenylephrine hydrochloride (PE HCl) is widely used for the treatment of nasal congestion, but efficacy at the 10-mg dose is not known for certain. The Food and Drug Administration has requested that sufficiently powered, multicenter, dose-ranging studies be conducted to assess the efficacy and safety of PE HCl. OBJECTIVE: To evaluate subjective nasal congestion symptom relief and safety of 4 different doses of PE HCl immediate-release 10-mg tablets and placebo in adults with seasonal allergic rhinitis (SAR). METHODS: This multicenter, phase 2, parallel, open-label trial randomized 539 adults with SAR (but otherwise healthy) to 7 days of treatment with either PE HCl 10-mg tablets at fixed doses of 10, 20, 30, or 40 mg or placebo. The primary efficacy end point was the mean change from baseline over the entire treatment period in daily reflective nasal congestion score. Other efficacy end points and safety were also evaluated. RESULTS: None of the PE HCl treatment groups had a statistically significant change from baseline in instantaneous or reflective nasal congestion scores compared with the placebo group. PE HCl was well tolerated at doses of up to 30 mg. At least 1 treatment-emergent adverse event was experienced by 18.4% of the participants, the most common being headache (3.0%). CONCLUSIONS: PE HCl, at doses of up to 40 mg every 4 hours, is not significantly better than placebo at relieving nasal congestion in adults with SAR. The phenylephrine section of the Food and Drug Administration monograph on over-the-counter cold, cough, allergy, bronchodilator, and antiasthmatic products should be revised accordingly. PMID- 26143021 TI - Growth References of Preschool Children Based on the Taiwan Birth Cohort Study and Compared to World Health Organization Growth Standards. AB - BACKGROUND: To develop new growth references for height, weight, and body mass index (BMI) for children aged 0-5 years in the Taiwan Birth Cohort Study (TBCS) and to compare these references with both 1997 Taiwan references and World Health Organization (WHO) standards. METHODS: Data were obtained from the TBCS of a nationally representative sample of 24,200 children. A total of 18,466 children completed the baseline survey at 6 months of age and three follow-up surveys at 18 months, 3 years, and 5.5 years of age. The modified LMS method was used to construct percentile curves by sex, including length/height for age, weight for age, and BMI for age. RESULTS: TBCS children of both sexes were shorter and lighter at birth compared with 1997 Taiwan references and WHO standards. The growth patterns of TBCS children were close to those of the 1997 Taiwan references after 6 months of age. Compared with WHO standards, however, TBCS children were heavier after 6 months of age. CONCLUSION: This study has developed TBCS references to monitor the growth of children in Taiwan, whose weight growth patterns differed from those "prescribed" by WHO standards. PMID- 26143020 TI - Drug-Induced Anaphylaxis in Latin American Countries. AB - BACKGROUND: Information regarding the clinical features and management of drug induced anaphylaxis (DIA) in Latin America is lacking. OBJECTIVE: The objective of this study was to assess implicated medications, demographics, and treatments received for DIA in Latin American patients referred to national specialty centers for evaluation. METHOD: A database previously used to compile information on drug-induced allergic reactions in 11 Latin American countries was used to identify and characterize patients presenting specifically with a clinical diagnosis of DIA. Information regarding clinical presentation, causative agent(s), diagnostic studies performed, treatment, and contributing factors associated with increased reaction severity was analyzed. RESULTS: There were 1005 patients evaluated for possible drug hypersensitivity reactions during the study interval, and 264 (26.3%) met criteria for DIA. DIA was more frequent in adults and in elderly females (N = 129 [76.6%] and N = 30 [75%], respectively) compared with children and/or adolescents (N = 21 [42.9%], P < .01). Severe DIA was less frequent with underlying asthma (N = 22 vs 35 [38.6% vs 61.4%], P < .05) or atopy (N = 62 vs 71 [43% vs 59% ], P < .01). Nonsteroidal anti-inflammatory drugs (NSAIDs) (N = 178 [57.8%]), beta-lactam antibiotics (N = 44 [14.3%]), and other antibiotics (N = 16 [5.2%]) were the most frequently implicated drug classes. Anaphylaxis was rated as severe in N = 133 (50.4%) and anaphylactic shock (AS) was present in N = 90 (34.1%). Epinephrine was only used in N = 73 (27.6%) overall, but in N = 70 (77.8%) of patients with AS. CONCLUSION: In Latin American patients referred for evaluation of DIA, NSAIDs and antibiotics were implicated in approximately 80% of cases. Most of these reactions were treated in the emergency department. Epinephrine was administered in only 27.6% of all cases, although more frequently for anaphylactic shock. Dissemination of anaphylaxis guidelines among emergency department physicians should be encouraged to improve management of DIA. PMID- 26143023 TI - Conceptual and Procedural Shortcomings of the Systematic Review "Evidence That Transcranial Direct Current Stimulation (tDCS) Generates Little-to-no Reliable Neurophysiologic Effect Beyond MEP Amplitude Modulation in Healthy Human Subjects: A Systematic Review" by Horvath and Co-workers. PMID- 26143022 TI - Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression. AB - BACKGROUND: Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events. OBJECTIVE/HYPOTHESIS: To examine efficacy, safety, and tolerability of low-field magnetic stimulation synchronized to an individual's alpha frequency (IAF) (synchronized TMS, or sTMS) for treatment of MDD. METHODS: Six-week double-blind sham-controlled treatment trial of a novel device that used three rotating neodymium magnets to deliver sTMS treatment. IAF was determined from a single-channel EEG prior to first treatment. Subjects had baseline 17-item Hamilton Depression Rating Scale (HamD17) >= 17. RESULTS: 202 subjects comprised the intent-to-treat (ITT) sample, and 120 subjects completed treatment per-protocol (PP). There was no difference in efficacy between active and sham in the ITT sample. Subjects in the PP sample (N = 59), however, had significantly greater mean decrease in HamD17 than sham (N = 60) (-9.00 vs. -6.56, P = 0.033). PP subjects with a history of poor response or intolerance to medication showed greater improvement with sTMS than did treatment naive subjects (-8.58 vs. -4.25, P = 0.017). Efficacy in the PP sample reflects exclusion of subjects who received fewer than 80% of scheduled treatments or were inadvertently treated at the incorrect IAF; these subgroups failed to separate from sham. There was no difference in adverse events between sTMS and sham, and no serious adverse events attributable to sTMS. CONCLUSIONS: Results suggest that sTMS may be effective, safe, and well tolerated for treating MDD when administered as intended. PMID- 26143024 TI - Multi-scalar residential context and recovery from illness: An analysis using Swedish register data. AB - The aim of this paper is to analyse if recovery from ill-health is influenced by geographical context using a multi-scalar approach to context measurement and Swedish longitudinal register-based data on sickness benefit recipiency as an indicator of onset of and recovery from illness. Our sample consists of individuals that have stayed healthy and in work for a three-year period (2000 2002) and then falls ill during the fourth year (2003), some of who recover to good health in the fifth year (2004). The results show that in areas with above average percentages of people receiving sickness-benefit there is a reduced probability of recovery. In contrast, high levels of employment in the neighbourhood and in the local area have a positive effect on the chances of recovery. These contextual effects are statistically significant but relatively weak in comparison to the influence of individual level factors such as age, sex, marital status, and income. Our conclusion is that individualised scalable neighbourhoods constitute a potentially valuable addition to the toolbox used in neighbourhood effect studies. PMID- 26143026 TI - Ebola fever epidemic 2014: a call for sustainable health and development policies. AB - In 2014 an Ebola epidemic emerged in Western Africa (particularly in Guinea, Liberia, Sierra Leone), which with regard to incidence and prevalence exceeded any previous Ebola epidemic [1]. According to estimates of the World Health Organization more than 26,000 people (including suspected cases) suffered from Ebola until April 2015. About 40% of them died from this infectious disease [2]. The dynamics and intensity of the epidemic took many experts by surprise. Above all, it represented excessive demands on local health care systems as well as--at least initially--of international organizations tasked with coordinated intervention [3]. From a health economic perspective, especially, the complete dysfunctionality of local health care services is not surprising. The Ebola fever epidemic in Western Africa rather reveals fundamental failures in establishing health policies within those countries as well as in development policies of industrialized nations. In the following, some of these structural defects are outlined and conclusions from the Ebola epidemic are drawn. PMID- 26143025 TI - Burden of influenza in Germany: a retrospective claims database analysis for the influenza season 2012/2013. AB - OBJECTIVE: Seasonal influenza occurs in annual epidemics. The virus can cause severe illness and concomitant diseases with the highest risk for children, the elderly, and individuals with disease dispositions. The study objective is to assess the influenza burden in Germany. METHODS: This retrospective claims data analysis used the Health Risk Institute research database containing anonymized data of 4 million individuals. The study period comprised the influenza season 2012/2013 in which patients with documented influenza were identified. Disease frequency rates were calculated for a population with disease dispositions and a population not at high risk. Disease burden was assessed based on health-services utilization during the influenza season. Vaccine rates were calculated by identifying vaccinations. RESULTS: We observed 65,826 patients with influenza, resulting in 1,160,646 documented influenza cases after extrapolation. Overall, otitis media and pneumonia was higher in the influenza-infected population compared to the non-influenza-infected population and especially high in children. Hospitalization cost amounted to ?87,202,485 with a mean stay of 7 days, and total outpatient costs were ?14,947,976. Vaccination rates were <4 % for children and 37 % for patients aged >60. CONCLUSIONS: Seasonal influenza can cause severe outcomes with hospitalizations and excess costs. Especially influenza-infected children are affected by concomitant diseases with higher disease burden. Furthermore, documented vaccination rates are quite low. PMID- 26143027 TI - Rubinstein-Taybi Syndrome. PMID- 26143028 TI - Functional Outcomes Following Bridge Plate Fixation for Distal Radius Fractures. AB - PURPOSE: To determine the functional outcomes of patients treated with dorsal spanning distraction bridge plate fixation for distal radius fractures. METHODS: All adult patients at our institution who underwent treatment of a unilateral distal radius fracture using a dorsal bridge plate from 2008 to 2012 were identified retrospectively. Patients were enrolled in clinical follow-up to assess function. Wrist range of motion, grip strength, and extension torque were measured systematically and compared with the contralateral, uninjured wrist. Patients also completed Quick-Disabilities of the Arm, Shoulder, and Hand and Patient-Rated Wrist Evaluation outcomes questionnaires. RESULTS: Eighteen of 100 eligible patients, with a minimum of 1 year from the time of implant removal, were available for follow-up (mean, 2.7 y). All fracture patterns were comminuted and intra-articular (AO 23.C3). There were significant decreases in wrist flexion (43 degrees vs 58 degrees ), extension (46 degrees vs 56 degrees ), and ulnar deviation (23 degrees vs 29 degrees ) compared with the contralateral uninjured wrist. Grip strength was 86% and extension torque was 78% of the contralateral wrist. Comparison of dominant and nondominant wrist injuries identified nearly complete recovery of grip (95%) and extension (96%) strength of dominant-sided wrist injuries, compared with grip (79%) and extension (65%) strength in those with an injured nondominant wrist. Mean Quick-Disabilities of the Arm, Shoulder, and Hand and Patient-Rated Wrist Evaluation scores were 16 and 14, respectively. There were 2 cases of postoperative surgical site pain and no cases of infection, tendonitis, or tendon rupture. CONCLUSIONS: Distraction bridge plate fixation for distal radius fractures is safe with minimal complications. Functional outcomes are similar to those published for other treatment methods. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26143029 TI - Scapholunate Interosseous Ligament Anatomy and Biomechanics. AB - Injury to the scapholunate interosseous ligament is one of the most common causes of carpal instability and can impart considerable compromise to the patient's hand function. However, the management of scapholunate ligament injuries remains a dynamic concept, especially with regard to the multitude of options and techniques that exist for its surgical treatment. We present a thorough review of scapholunate anatomy and morphology, and the role of the scapholunate articulations in the kinetics and pathomechanics of wrist instability. We also review the current literature on the biomechanical properties of the scapholunate ligament and its subcomponents. A sound understanding of the anatomy and biomechanics of the scapholunate ligament can clarify its instability and may better orient current reconstructive procedures or pioneer better future techniques. PMID- 26143030 TI - An Overview of Internal Fixation Implant Metallurgy and Galvanic Corrosion Effects. AB - Orthopedic and hand surgery implants for internal fixation of fractures have evolved substantially over the past 50 years. Newer metal compositions have been used, and new standards have been applied to older alloys, resulting in modern implants with unique physical properties and better clinical performances. Conventional wisdom has long dictated that implanting different metals should be avoided, but few guidelines exist regarding the safety of using in proximity implant systems of dissimilar metals. To better characterize the landscape of internal fixation implant metallurgy, we have compiled the recommendations and conclusions of the currently available and pertinent literature. PMID- 26143031 TI - Erratum to: Association of chromosome 19 to lung cancer genotypes and phenotypes. AB - Erratum to: Cancer and Metastasis Review, DOI 10.1007/s10555-015-9556-2. There are changes in authors' affiliations and a new affiliations for Carol L. Nilsson and Thomas E. Fehniger has been added. The corresponding author also missed out to include Peter Horvatovich as a co-author of this work. The complete list of authors is now listed above. PMID- 26143032 TI - Contagion 2.0. PMID- 26143033 TI - Formation of chitosan-fucoidan nanoparticles and their electrostatic interactions: Quantitative analysis. AB - The stoichiometric distributions of both positive amino groups and negative sulfate ions loaded in chitosan-fucoidan nanoparticles (CFNs) were predicted quantitatively by correlating the separate yields of loaded chitosan and fucoidan, and a proposed relative charge density model (case 1). In addition, those distributions of both positive amino groups and negative sulfate ions loaded in CFNs were obtained by deriving the expression of their loaded concentrations directly from the experimental data (case 2). Both the model prediction and experimental derivations were remarkably consistent with each other except at pH 2. The discrepancy between cases 1 and 2 at pH 2 was explained by an increase in the sulfate group loading because of the most intensive electrostatic (specific ion) interactions at pH 2. The ratio of the CFN-free net charge density shielded by counter-ions in the solution entrapped in CFNs to their counter-ion-crosslinking charge density was suggested to be a quantitative criterion for determining the size distribution of CFNs. The formation of CFNs ranked according to size was predicted well and explained reasonably by the suggested criterion, considering both the ionic strength of the entrapped solution in CFNs and the nonspecific binding (interaction) of the positive amino groups among the chitosan molecules. Furthermore, the fraction of nonspecifically bound positive amino groups causing hysteresis was quantified from the positive net charged amino groups per unit-mass CFN. Thus, its magnitude was predicted to have a strong correlation with the CFN-preparation conditions, such as pH and fucoidan to chitosan mass ratio. PMID- 26143034 TI - Development of a rapid method to isolate polyhydroxyalkanoates from bacteria for screening studies. AB - We describe a novel method of Polyhydroxyalkanoate (PHA) extraction using dimethyl sulphoxide (DMSO) for use in screening studies. Compared to conventional chloroform extraction, the DMSO method was shown to release comparable quantities of PHA from Cupriavidus necator cells, with comparable properties as determined using Fourier transform infrared spectroscopy and differential scanning calorimetry. PMID- 26143035 TI - Inhibitory effects of sulfur compounds on methane oxidation by a methane oxidizing consortium. AB - Kinetic and enzymatic inhibition experiments were performed to investigate the effects of methanethiol (MT) and hydrogen sulfide (H2S) on methane oxidation by a methane-oxidizing consortium. In the coexistence of MT and H2S, the oxidation of methane was delayed until MT and H2S were completely degraded. MT and H2S could be degraded, both with and without methane. The kinetic analysis revealed that the methane-oxidizing consortium showed a maximum methane oxidation rate (Vmax) of 3.7 mmol g-dry cell weight (DCW)(-1) h(-1) and a saturation constant (Km) of 184.1 MUM. MT and H2S show competitive inhibition on methane oxidation, with inhibition values (Ki) of 1504.8 and 359.8 MUM, respectively. MT was primary removed by particulate methane monooxygenases (pMMO) of the consortium, while H2S was degraded by the other microorganisms or enzymes in the consortium. DNA and mRNA transcript levels of the pmoA gene expressions were decreased to ~10(6) and 10(3)pmoA gene copy number g-DCW(-1) after MT and H2S degradation, respectively; however, both the amount of the DNA and mRNA transcript recovered their initial levels of ~10(7) and 10(5)pmoA gene copy number g-DCW(-1) after methane oxidation, respectively. The gene expression results indicate that the pmoA gene could be rapidly reproducible after methane oxidation. This study provides comprehensive information of kinetic interactions between methane and sulfur compounds. PMID- 26143036 TI - Discriminative clustering via extreme learning machine. AB - Discriminative clustering is an unsupervised learning framework which introduces the discriminative learning rule of supervised classification into clustering. The underlying assumption is that a good partition (clustering) of the data should yield high discrimination, namely, the partitioned data can be easily classified by some classification algorithms. In this paper, we propose three discriminative clustering approaches based on Extreme Learning Machine (ELM). The first algorithm iteratively trains weighted ELM (W-ELM) classifier to gradually maximize the data discrimination. The second and third methods are both built on Fisher's Linear Discriminant Analysis (LDA); but one approach adopts alternative optimization, while the other leverages kernel k-means. We show that the proposed algorithms can be easily implemented, and yield competitive clustering accuracy on real world data sets compared to state-of-the-art clustering methods. PMID- 26143037 TI - Radiotherapy-induced xerostomia, pre-clinical promise of LMS-611. AB - PURPOSE: Radiotherapy-induced xerostomia (RIX) is the most common permanent side effect of radiotherapy (RT) to the head and neck (H&N). There is no effective topical treatment. LMS-611 is a mimetic of a natural lamellar body which prevents thick secretions like saliva from congesting organs. The primary objective of this study was to assess saliva properties before and during RT to the H&N. The secondary objectives were to re-assess saliva properties with the addition of LMS 611, measure inter-patient variability, correlate patient-reported symptoms with laboratory measurements and design subsequent first-in-human clinical trial of LMS-611. METHODS: Patients with H&N cancer receiving RT as primary treatment were recruited. Patients completed the Groningen RIX (GRIX) questionnaire and provided saliva samples at baseline and weeks 2, 4 and 6 of RT. Saliva adhesiveness and viscosity were tested by measuring time taken to travel 5 cm down an inclined plane. RESULTS: Thirty patients were enrolled. The inclined plane test (IPT) results (s) were as follows: baseline 31.3, week 2 49.7, week 4 51.1 and week 6 55.7. Wide inter-patient variability was seen at baseline. GRIX scores increased as RT progressed. Spearman rank correlation coefficient of inclined plane tests with GRIX scores was -0.06 at baseline, 0.25 at week 2, 0.12 at week 4 and 0.08 at week 6. LMS-611 concentrations of 10 and 20 mg/ml significantly reduced IPT times on saliva samples. CONCLUSIONS: Saliva becomes more visco-adhesive and RIX worsens as RT progresses. There is little correlation between objective and subjective measures of RIX. The addition of LMS-611 to thick, sticky saliva restores its fluidity ex vivo. This warrants in vivo analysis of the effect of LMS-611 upon RIX. PMID- 26143038 TI - Pre-diagnosis employment status and financial circumstances predict cancer related financial stress and strain among breast and prostate cancer survivors. AB - PURPOSE: Cancer may have a significant financial impact on patients, but the characteristics that predispose patients to cancer-related financial hardship are poorly understood. We investigated factors associated with cancer-related financial stress and strain in breast and prostate cancer survivors in Ireland, which has a complex mixed public-private healthcare system. METHODS: Postal questionnaires were distributed to 1373 people diagnosed with cancer 3-24 months previously identified from the National Cancer Registry Ireland. Outcomes were cancer-related financial stress (impact of cancer diagnosis on household ability to make ends meet) and financial strain (concerns about household financial situation since cancer diagnosis). Modified Poisson regression was used to estimate relative risks (RR) for factors associated with cancer-related financial stress and strain. RESULTS: Seven hundred forty survivors participated (response rate = 54 %). Of the respondents, 48 % reported cancer-related financial stress and 32 % cancer-related financial strain. Compared to those employed at diagnosis, risk of cancer-related financial stress was significantly lower in those not working (RR = 0.71, 95 % CI 0.58-0.86) or retired (RR = 0.48, 95 % CI 0.34-0.68). It was significantly higher in those who had dependents; experienced financial stress pre-diagnosis; had a mortgage/personal loans; had higher direct medical out-of-pocket costs; and had increased household bills post-diagnosis. For cancer-related financial strain, significant associations were found with dependents, pre-diagnosis employment status and pre-diagnosis financial stress; risk was lower in those with higher direct medical out-of-pocket costs. CONCLUSIONS: Cancer-related financial stress and strain are common. Pre-diagnosis employment status and financial circumstances are important predictors of post diagnosis financial wellbeing. These findings could inform development of tools to identify patients/survivors most in need of financial advice and support. PMID- 26143039 TI - Skeletal related events in patients with bone metastasis arising from non-small cell lung cancer. AB - PURPOSE: The skeleton is one of the most common sites of metastasis in patients with non-small cell lung cancer (NSCLC). Metastasis increases the risk of skeletal-related events (SREs). The purpose of this study is to evaluate the incidence of SREs and the factors associated with the development of SREs in patients with bone metastases (BM) arising from NSCLC. METHODS: A cohort study was carried out involving 95 patients with BM associated with NSCLC who were enrolled between 2007 and 2011. Clinical and sociodemographic data were extracted from the physical and electronic records. The association between exposure variables and outcome (SREs) was assessed using crude odds ratio (OR). Survival analysis of patients with BM was conducted using the Kaplan-Meier method. A log rank test was used to assess differences between the curves of those who did and did not experience SREs. RESULTS: Sixty-two out of 95 patients with BM (65.3 %) showed evidence of at least one SRE. Multiple analysis revealed that patients with a history of smoking (OR = 6.76; 95% CI = 1.3-33.0; p < 0.01), performance status >=2 (OR = 3.38; 95% CI = 1.2-9.3; p < 0.01), and multiple BM (OR = 3.31; 95% CI = 1.1-9.9; p < 0.03) were at greater risk of SREs. Median survival time was 4.6 months (95% CI = 2.9-6.2) in patients who experienced SREs and 6.8 months (95% CI = 2.2-11.4) in patients who did not, a statistically significant difference (p = 0.03). CONCLUSION: Patients with NSCLC are more likely to experience SREs if they have poor performance status, a history of smoking or multiple BM. Global survival was shorter in patients who suffer SREs. PMID- 26143040 TI - Cancer and quality of life in spousal dyads: spillover in couples with and without cancer-related health problems. AB - PURPOSE: Poor health of one spouse can adversely influence the partner's health outcomes ("spillover"). This study aimed to estimate quality of life spillover among spouses and to determine how presence of cancer influenced these effects. METHODS: We examined data on husband-wife dyads with cancer-related health problems, medical events, or disabilities (n = 910) and matched comparison dyads from the 2004-2012 Medical Expenditures Panel Survey, a population-based survey of the USA. Mental and physical health-related quality of life and depressed mood were reported at two time points (T1 and T2, 11 months apart on average). Dyadic multilevel models evaluated the cross-lagged impact of HRQoL and depressed mood at T1 on spouses' HRQoL at T2, controlling for sociodemographics and health conditions. RESULTS: Small but statistically significant spillover was observed for mental and physical HRQoL among couples with cancer. Spillover occurred from both the spouse to the survivor and from survivor to spouse. Depressed mood, in particular, showed stronger spillover effects from the spouse to the survivor than the inverse. Similar effects were not observed in dyads without cancer. CONCLUSIONS: Screening for and treating poor HRQoL and depressed mood concurrently in both cancer survivors, and their spouses may positively influence HRQoL outcomes. Future research is needed to further elucidate these findings and determine whether a concurrent approach to psychosocial care in survivors and their spouses may improve long-term outcomes. PMID- 26143041 TI - Consistent use of precise language decreases misunderstandings. PMID- 26143042 TI - Transcriptome-wide analysis of the response of the thecosome pteropod Clio pyramidata to short-term CO2 exposure. AB - Thecosome pteropods, a group of calcifying holoplanktonic mollusks, have recently become a research focus due to their potential sensitivity to increased levels of anthropogenic dissolved CO2 in seawater and the accompanying ocean acidification. Some populations, however, already experience high CO2 in their natural distribution during diel vertical migrations. To achieve a better understanding of the mechanisms of pteropod calcification and physiological response to this sort of short duration CO2 exposure, we characterized the gene complement of Clio pyramidata, a cosmopolitan diel migratory thecosome, and investigated its transcriptomic response to experimentally manipulated CO2 conditions. Individuals were sampled from the Northwest Atlantic in the fall of 2011 and exposed to ambient conditions (~380ppm) and elevated CO2 (~800ppm, similar to levels experienced during a diel vertical migration) for ~10h. Following this exposure the respiration rate of the individuals was measured. We then performed RNA-seq analysis, assembled the C. pyramidata transcriptome de novo, annotated the genes, and assessed the differential gene expression patterns in response to exposure to elevated CO2. Within the transcriptome, we identified homologs of genes with known roles in biomineralization in other mollusks, including perlucin, calmodulin, dermatopontin, calponin, and chitin synthases. Respiration rate was not affected by short-term exposure to CO2. Gene expression varied greatly among individuals, and comparison between treatments indicated that C. pyramidata down regulated a small number of genes associated with aerobic metabolism and up regulated genes that may be associated with biomineralization, particularly collagens and C-type lectins. These results provide initial insight into the effects of short term CO2 exposure on these important planktonic open-ocean calcifiers, pairing respiration rate and the gene expression level of response, and reveal candidate genes for future ecophysiological, biomaterial and phylogenetic studies. PMID- 26143043 TI - [Microbiological characteristics and patterns of resistance in prosthetic joint infections in a referral hospital]. AB - BACKGROUND: The prosthetic joint infection is the most feared and catastrophic complication for cause severe physical damage to patients and, generates high economic costs. OBJECTIVES: To describe the microbiological characteristics and to determine the resistance pattern in prosthetic joint infections in a reference hospital in Mexico. MATERIAL AND METHODS: Patients whose prosthetic devices were withdrawn due to suspicion of septic and aseptic loosening were included. Cultures were performed to identify microorganisms and susceptibility analysis. RESULTS: Of the 111 patients included, 55% were diagnosed with prosthetic joint infection, with the most frequent prosthesis being of the hip (43%). Positive cultures were obtained in 97% of the infected cases, of which 75% were monomicrobial infections. The most frequent bacterial species isolated were: Staphylococcus epidermidis (31%), Enterococcus faecalis (16%), Staphylococcus aureus (13%), and Escherichia coli (8%). The resistance patterns for the Staphylococcus genus were: oxacillin (79%), erythromycin (45%) and ciprofloxacin (37%). Enterococcus faecalis showed a high percentage of resistance to erythromycin and clindamycin (86%), and fluoroquinolones (43%). The large majority (86%) of Escherichia coli were extended spectrum beta-lactamases positive, in addition to having high resistance to fluoroquinolones (86%), trimethoprim/sulfamethoxazole (86%) and gentamicin (72%). CONCLUSION: The microbiological characteristics found in prosthetic joint infections vary according to the hospitals. In this series, a high proportion of coagulase negative Staphylococci and Enterococcus spp. were found, as well as a high bacterial resistance. PMID- 26143044 TI - Editorial overview: host-microbe interactions: parasites. PMID- 26143045 TI - [Motor nerves of the face. Surgical and radiologic anatomy of facial paralysis and their surgical repair]. AB - Motor innervation of the face depends on the facial nerve for the mobility of the face, on the mandibular nerve, third branch of the trigeminal nerve, which gives the motor innervation of the masticator muscles, and the hypoglossal nerve for the tongue. In case of facial paralysis, the most common palliative surgical techniques are the lengthening temporalis myoplasty (the temporal is innervated by the mandibular nerve) and the hypoglossal-facial anastomosis. The aim of this work is to describe the surgical anatomy of these three nerves and the radiologic anatomy of the facial nerve inside the temporal bone. Then the facial nerve penetrates inside the parotid gland giving a plexus. Four branches of the facial nerve leave the parotid gland: they are called temporal, zygomatic, buccal and marginal which give innervation to the cutaneous muscles of the face. Mandibular nerve gives three branches to the temporal muscles: the anterior, intermediate and posterior deep temporal nerves which penetrate inside the deep aspect of the temporal muscle in front of the infratemporal line. The hypoglossal nerve is only the motor nerve to the tongue. The ansa cervicalis, which is coming from the superficial cervical plexus and joins the hypoglossal nerve in the submandibular area is giving the motor innervation to subhyoid muscles and to the geniohyoid muscle. PMID- 26143046 TI - Facial paralysis and the role of free muscle transplantation. AB - Facial paralysis can have significant functional, psychological and aesthetic concerns that alter the lives of our patients. These effects can be functional, affecting the eye, nose and mouth, or aesthetic, affecting the symmetry of the face and particularly the mimetic function of smile. Several reanimation procedures have been described to address this. In this chapter, we will outline our technique for reanimation utilizing segmental gracilis muscle transplants to the face. These are innervated either by the contralateral normal 7th nerve via a cross face nerve graft, or a different ipsilateral motor where no 7th nerve is available or would not produce the required result. The other ipsilateral motor that we have found extremely effective is the motor nerve to masseter. This can power a segmental gracilis muscle transplant and lead to excursion that is near normal. These techniques will be described in detail. PMID- 26143047 TI - [Rehabilitation of facial paralysis using autogenous fascia lata graft. Stable results over time]. AB - Dynamic facial reanimation with free muscle or nerve transfers represents the mainstay of facial paralysis treatments particularly for perioral area and smile. These techniques are not always feasible, in such cases we perform a perioral suspension with fascia lata graft. However many teams blame this technique for short-term recurrence of the deformity. We describe in this paper details of our surgical technique, to improve the aesthetic result and stability over time, and the results and complications encountered. Fascia lata graft was sutured beyond the midline to the contralateral healthy lips, after tunneling through upper and lower orbicularis oris. Fascia lata graft was then tunneled through the buccal fat pad, then under the zygomatic arch to the temporal region, where the temporal aponeurosis was incised to make way for the fascia lata graft, which was fixed to the outer face of the temporal aponeurosis, applying slight overcorrection to the oral commissure. From 2003 to 2012, we performed this procedure on 8 patients. Results showed an immediate aesthetic improvement, stable over time. Perioral suspension with fascia lata graft is a surgical alternative when dynamic reanimation is not feasible. PMID- 26143048 TI - [Breast reconstruction with Profunda Artery Perforator flap in lithotomy position. Surgical technique]. AB - Autologous breast reconstruction provides great cosmetic, functional and sustainable incomes. Various flaps have been described in autologous breast reconstruction, Deep Inferior Epigastric Perforator flap (DIEP) being the most frequent. For patients with a non-sufficient abdomen for a DIEP based breast reconstruction, the Profunda Artery Perforator Flap (PAP), based on profunda arteris perforators, is a current trend, but few publications detailed the flap harvest. Comparing with a TUG flap, the morbidity linked to the muscle harvest is decreased. Usually the dissection is done in prone or in "frog leg" position. The aim is to describe a technical option: we propose a different position, with a harvest of the PAP in lithotomy position. It offers additional comfort and security for the surgeon and decreases the operative time. The pedicle had an average of 7cm in length; the artery diameter was 2.2mm and the vein 2.5mm. The cosmetic incomes are very good six months postoperative. PMID- 26143049 TI - Microbiologic clearance following transition from standard infusion piperacillin tazobactam to extended-infusion for persistent Gram-negative bacteremia and possible endocarditis: A case report and review of the literature. AB - INTRODUCTION: We sought to describe a case of pharmacodynamically-optimized dosing of piperacillin-tazobactam in a patient that cleared their infections after treatment with high-dose, extended-infusion piperacillin-tazobactam and summarize the literature on the benefits of extended-infusion of beta-lactams. CASE REPORT: At an outside hospital, a 78 year-old male presented with fevers and shortness of breath. He was empirically initiated on standard doses of vancomycin and piperacillin-tazobactam for suspected pneumonia and sepsis. Blood and sputum cultures identified Elizabethkingia meningosepticum sensitive only to piperacillin-tazobactam by E-test susceptibility testing. After 10 days of empiric therapy with piperacillin-tazobactam dosed at 3.375 g IV every 8 h over 30 min, the patient transferred to our institution and was initiated on piperacillin-tazobactam at 3.375 g IV every 8 h administered as a 4 h infusion. The patient failed to improve; piperacillin-tazobactam was changed to 4.5 g IV over 4 h every 8 h and later changed to the hospital protocol dose of 3.375 g IV over 4 h every 6 h. The patient achieved negative blood cultures within 24 h of optimized dosing. DISCUSSION: We present the first case to our knowledge that describes failure to respond and subsequent response within a single patient where beta-lactam dosing was altered to optimize pharmacokinetics and pharmacodynamics (PK-PD). Our patient received non-standard dose-escalation for piperacillin-tazobactam. Drug exposure was estimated post-hoc utilizing robust mathematical simulations to describe alterations in disposition over time. This case demonstrates that extended-infusion administration of beta-lactams may provide improved microbiological activity. PMID- 26143050 TI - Prelimbic cortex 5-HT1A and 5-HT2C receptors are involved in the hypophagic effects caused by fluoxetine in fasted rats. AB - The regulation of food intake involves a complex interplay between the central nervous system and the activity of organs involved in energy homeostasis. Besides the hypothalamus, recognized as the center of this regulation, other structures are involved, especially limbic regions such as the ventral medial prefrontal cortex (vMPFC). Monoamines, such as serotonin (5-HT), play an important role in appetite regulation. However, the effect in the vMPFC of the selective serotonin reuptake inhibitor (SSRI), fluoxetine, on food intake has not been studied. The aim of the present study was to study the effects on food intake of fed and fasted rats evoked by fluoxetine injection into the prelimbic cortex (PL), a sub region of the vMPFC, or given systemically, and which 5-HT receptors in the PL are involved in fluoxetine responses. Fluoxetine was injected into the PL or given systemically in male Wistar rats. Independent groups of rats were pretreated with intra-PL antagonists of 5-HT receptors: 5-HT1A (WAY100635), 5 HT2C (SB242084) or 5-HT1B (SB216641). Fluoxetine (0.1; 1; 3; 10nmol/200nL) injected into the PL induced a dose-dependent hypophagic effect in fasted rats. This effect was reversed by prior local treatment with WAY100635 (1; 10nmol) or SB242084 (1; 10nmol), but not with SB216641 (0.2; 2.5; 10nmol). Systemic fluoxetine induced a hypophagic effect, which was blocked by intra-PL 5-HT2C antagonist (10nmol) administration. Our findings suggest that PL 5-HT neurotransmission modulates the central control of food intake and 5-HT1A and 5 HT2C receptors in the PL could be potential targets for the action of fluoxetine. PMID- 26143051 TI - Analysis of aliphatic waxes associated with root periderm or exodermis from eleven plant species. AB - Aliphatic waxes can be found in association with suberized tissues, including roots. Non-polar lipids were isolated by rapid solvent extraction of mature regions of intact roots from eleven angiosperms, including both monocots and dicots. The majority of roots analyzed were taproots or tuberous taproots that had undergone secondary growth and thus were covered by a suberized periderm. The exceptions therein were maize (Zea mays L.) and rice (Oryza sativa L.), which present a suberized exodermis. The analysis herein focused on aliphatic waxes, with particular emphasis on alkyl hydroxycinnamates (AHCs). AHCs were widely distributed, absent from only one species, were found in both aerial and subterranean portions of tuberous taproots, and were associated with the fibrous roots of both maize and rice. Most species also contained monoacylglycerols, fatty alcohols and/or free fatty acids. Carrot (Daucus carrota L.) was the outlier, containing only free fatty acids, sterols, and polyacetylenes as identified components. Sterols were the only ubiquitous component across all roots analyzed. Monoacylglycerols of omega-hydroxy fatty acids were present in maize and rice root waxes. For species within the Brassiceae, wax compositions varied between subspecies or varieties and between aerial and subterranean portions of taproots. In addition, reduced forms of photo-oxidation products of omega-hydroxy oleate and its corresponding dicarboxylic acid (10,18-dihydroxy octadec-8-enoate, 9,18-dihydroxy-octadec-10-enoate and 9-hydroxyoctadec-10-ene 1,18-dioate) were identified as naturally occurring suberin monomers in rutabaga (Brassica napus subsp. rapifera Metzg.) periderm tissues. PMID- 26143052 TI - Results of an Active Neurodynamic Mobilization Program in Patients With Fibromyalgia Syndrome: A Randomized Controlled Trial. AB - OBJECTIVE: To examine the effects of an active neurodynamic mobilization program on pain, neurodynamics, perceived health state, and fatigue in patients with fibromyalgia syndrome (FMS). DESIGN: Randomized controlled trial. SETTING: Local fibromyalgia association. PARTICIPANTS: Patients with FMS (N=48). INTERVENTIONS: Patients were randomly allocated to an active neurodynamic mobilization program or a control group. The intervention was performed twice a week. MAIN OUTCOME MEASURES: Pain was assessed with the Brief Pain Inventory and Pain Catastrophizing Scale; neurodynamics were evaluated using neurodynamic tests for upper and lower limbs. The functional state was evaluated with the Health Assessment Questionnaire Disability Index, and perceived fatigue was evaluated with the Fatigue Severity Scale. RESULTS: Significant (P<.05) between-groups differences were found in the values of pain, upper and lower limb neurodynamics, functional state, and fatigue. Also, significant pre- to postintervention within group differences were found in the intervention group, whereas no significant changes were found in the control group. CONCLUSIONS: A neurodynamic mobilization program is effective in improving pain, neurodynamics, functional status, and fatigue in patients with FMS. PMID- 26143053 TI - Agreement Between Physician's Recommendation and Fitness-to-Drive Decision in Multiple Sclerosis. AB - OBJECTIVE: To investigate the agreement of fitness-to-drive decisions made by the referring physicians and by the on-road assessors in individuals with multiple sclerosis (MS). DESIGN: Retrospective analysis. SETTING: Driving institute. PARTICIPANTS: A sample of individuals with MS (N=218) who completed the medical and driving questionnaire and performed an official on-road test. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Fitness-to-drive decision made by the on road assessor. RESULTS: The referring physician and on-road assessor agreed on fitness to drive in 191 (88%) of the cases (prevalence-adjusted and bias-adjusted kappa=.81, P<.0001). When compared with the on-road assessor's judgment, the physician's recommendation of fitness to drive was overestimated in 16 individuals with MS and underestimated in 11 individuals with MS. Patients with poor binocular acuity were more likely to be inaccurately classified by the physician (P=.001). CONCLUSIONS: This study showed a high level of agreement between the fitness-to-drive decisions made by the physicians and the on-road assessors in individuals with MS. Visual functions should be assessed in the doctor's office for more accurate referrals. PMID- 26143054 TI - How Do Fugl-Meyer Arm Motor Scores Relate to Dexterity According to the Action Research Arm Test at 6 Months Poststroke? AB - OBJECTIVE: To determine the optimal cutoff scores for the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) with regard to predicting no, poor, limited, notable, or full upper-limb capacity according to frequently used cutoff points for the Action Research Arm Test (ARAT) at 6 months poststroke. DESIGN: Prospective. SETTING: Rehabilitation center. PARTICIPANTS: Patients (N=460) with a first-ever ischemic stroke at 6 months poststroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Based on the ARAT classification of poor to full upper-limb capacity, receiver operating characteristic curves were used to calculate the area under the curve, optimal cutoff points for the FMA-UE were determined, and a weighted kappa was used to assess the agreement. RESULTS: FMA UE scores of 0 through 22 represent no upper-limb capacity (ARAT 0-10); scores of 23 through 31 represent poor capacity (ARAT 11-21); scores of 32 through 47 represent limited capacity (ARAT 22-42); scores of 48 through 52 represent notable capacity (ARAT 43-54); and scores of 53 through 66 represent full upper limb capacity (ARAT 55-57). Overall, areas under the curve ranged from .916 (95% confidence interval [CI], .890-.943) to .988 (95% CI, .978-.998; P<.001). CONCLUSIONS: There is considerable overlap in the area under the curve between the ARAT and FMA-UE. FMA-UE scores >31 points correspond to no to poor arm-hand capacity (ie, <=21 points) on the ARAT, whereas FMA-UE scores >31 correspond to limited to full arm-hand capacity (ie, >=22 points) on the ARAT. PMID- 26143055 TI - Effect of Cinnamic Acid for Controlling Gray Mold on Table Grape and Its Possible Mechanisms of Action. AB - Cinnamic acid (CA) is an organic acid and is widely used in food industry as a common food additive. Previous studies showed that CA has the antimicrobial activity in vitro, but little is known about the effect of CA on controlling the fruit decay in vivo. In present study, we showed that application of CA was significantly effective on controlling the gray mold of table grape caused by Botrytis cinerea. CA can directly inhibit the mycelial growth of B. cinerea on potato dextrose agar plates. The mechanisms by which CA inhibited fungal growth were assayed by staining the spores with fluorescent dyes propidium iodide and 7 dichlorodihydrofluorescein diacetate, respectively. The results indicated that CA can damage the integrity of plasma membrane and induce the intracellular reactive oxygen species level of B. cinerea which were responsible for the reduction of growth rate. Meanwhile, CA treatment significantly stimulated the activities of peroxidase and polyphenol oxidase which were closely related to the resistance of plant. Taken together, this study suggested that CA was effective on controlling the gray mold of table grape in postharvest period by inhibiting the growth of pathogen and inducing the resistance of host. PMID- 26143056 TI - Enterobacter Strains Might Promote Colon Cancer. AB - Many studies have been performed to determine the interaction between bacterial species and cancer. However, there has been no attempts to demonstrate a possible relationship between Enterobacter spp. and colon cancer so far. Therefore, in the present study, it is aimed to investigate the effects of Enterobacter strains on colon cancer. Bacterial proteins were isolated from 11 Enterobacter spp., one Morganella morganii, and one Escherichia coli strains, and applied onto NCM460 (Incell) and CRL1790 (ATCC) cell lines. Cell viability and proliferation were determined in MTS assay. Flow Cytometry was used to detect CD24 level and apoptosis. Real-Time PCR studies were performed to determine NFKB and Bcl2 expression. Graphpad Software was used for statistical analysis. The results showed that proteins, isolated from the Enterobacter spp., have significantly increased cell viability and proliferation, while decreasing the apoptosis of the cell lines tested. The data in the present study indicated that Enterobacter strains might promote colon cancer. Moreover, Enterobacter spp. could be a clinically important factor for colon cancer initiation and progression. Studies can be extended on animal models in order to develop new strategies for treatment. PMID- 26143057 TI - Structural and functional measures of social relationships and quality of life among older adults: does chronic disease status matter? AB - PURPOSE: To evaluate the relative importance of structural and functional social relationships for quality of life (QoL) and the extent to which diagnosed chronic disease modifies these associations. METHODS: Multivariate linear regression was used to investigate time-lagged associations between structural and functional measures of social relationships and QoL assessed 5 years apart by CASP-19, in 5925 Whitehall II participants (mean age 61, SD 6.0). Chronic disease was clinically verified coronary heart disease, stroke, diabetes or cancer. RESULTS: Social relationships-QoL associations were consistent across disease status (P values for interaction: 0.15-0.99). Larger friend network (beta = 1.9, 95% CI 1.5 2.3), having a partner (beta = 1.2, 95% CI 0.5-1.7), higher confiding support (beta = 2.2, 95% CI 1.8-2.7) and lower negative aspects of close relationships (beta = 3.3, 95% CI 2.8-3.8) were independently related to improved QoL in old age. The estimated difference in QoL due to social relationships was equivalent to up to 0.5 SD of the CASP-19 score and was stronger than the effect of chronic disease (coronary heart disease beta = 2.0, 95% CI 1.4-2.6). CONCLUSIONS: We found that beneficial aspects of social relationships in relation to QoL were, in order of importance: avoiding negative aspects of close relationships, having confiding support, having a wide network of friends and having a partner. These associations were not modified by chronic disease. Thus, despite inevitable physical deterioration, we may be able to enhance a satisfying late life by optimizing our social relationships. PMID- 26143059 TI - The role of direct high-resolution mass spectrometry in foodomics. AB - Foodomics has been defined as a global discipline in which advanced analytical techniques and bioinformatics are combined to address different questions in food science and nutrition. There is a growing number of works on the development and application of non-targeted omics methods in foodomics, which reflects that this emerging discipline is already considered by the scientific community to be a valuable approach to assess food safety, quality, and traceability as well as for the study of the links between food and health. As a result, there is a clear need for more rapid, high-throughput MS approaches for developing and applying non-targeted studies. Nowadays, direct MS analysis is one of the main choices to achieve high throughput, generating a set of information from the largest possible number of samples in a fast and straightforward way. The use of high- and ultrahigh-resolution MS greatly improves the analytical performance and offers a good combination of selectivity and sensitivity. By using a range of methods for direct sample introduction/desorption/ionization, high-throughput and non-target analysis of a variety of samples can be obtained in a few seconds by HRMS analysis. In this review, a general overview is presented of the main characteristics of direct HRMS-based approaches and their principal applications in foodomics. PMID- 26143058 TI - Health-related quality of life in patients with prominent negative symptoms: results from a multicenter randomized Phase II trial on bitopertin. AB - PURPOSE: Symptoms of schizophrenia fall into three categories (positive, negative and cognitive symptoms), which probably impact differently on patient's health related quality of life (HRQoL). The present study aimed to explore HRQoL in patients with prominent negative symptoms. METHODS: In the 323 patients with prominent negative symptoms included in a multicenter Phase II trial investigating the safety and efficacy of bitopertin, HRQoL was assessed using the Schizophrenia Quality of Life Scale (SQLS), symptoms severity using the Positive and Negative Syndrome Scale and functioning using the Personal and Social Performance Scale. SQLS measurement properties were assessed; HRQoL was compared between treatment arms, and relationships between HRQoL, symptoms and functioning at baseline were explored. RESULTS: Both SQLS scores (Vitality/Cognition and Psychosocial Feelings) demonstrated good test-retest (ICC = 0.77 and 0.74) and internal consistency reliability (Cronbach's alpha = 0.86 and 0.93). Clinical validity with regard to schizophrenia severity and ability to detect change in severity of symptoms of schizophrenia were satisfactory. The SQLS structure was not formally disconfirmed. No statistically significant difference was observed between treatment arms. Negative symptoms were more strongly associated with functioning than positive symptoms. Functioning and Anxiety/Depression were strongly related to both SQLS domains. CONCLUSION: Overall, SQLS measurement properties were supported in these patients with prominent negative symptoms of schizophrenia. The impact of negative symptoms on functioning and HRQoL suggests that improving these symptoms will be a meaningful benefit in this population of patients. PMID- 26143060 TI - CocoSoft: educational software for automation in the analytical chemistry laboratory. PMID- 26143061 TI - Counter-pressure-assisted ITP with electrokinetic injection under field-amplified conditions for bacterial analysis. AB - Counter-pressure was used to extend the duration of field-amplified sample injection in isotachophoresis (FASI-ITP) in order to improve the detection of bacterial cells. Using 0.51-MUm negatively charged encapsulated fluorescent beads as a model, the counter-pressure, injection and separation voltages, and times were optimized. Using 6-min 8,963-Pa counter-pressure FASI-ITP injections at -12 kV followed by mobilization of the ITP band with continued injection at -6 kV, the limit of detection (LOD) for Escherichia coli was improved to 78 cells/mL, a factor of 4 when compared with FASI-ITP without counter-pressure. PMID- 26143062 TI - Quantitative bile acid profiling by liquid chromatography quadrupole time-of flight mass spectrometry: monitoring hepatitis B therapy by a novel Na(+) taurocholate cotransporting polypeptide inhibitor. AB - A novel analytical approach for the targeted profiling of bile acids (BAs) in human serum/plasma based on liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) is presented. Reversed-phase chromatography enabled the baseline separation of 15 human BA species which could be readily detected by accurate mass analysis in negative ion mode. Blood proteins were removed by methanol precipitation in the presence of deuterium-labeled internal standards which allowed BA quantification in 50 MUl plasma/serum. The assay was validated according to FDA guidance achieving quantification limits from 7.8 to 156 nM. Calibration curves prepared in charcoal-stripped serum/plasma showed excellent regression coefficients (R (2) > 0.997) and covered quantities from 7.8 to 10,000 nM depending on the analyzed species. Intra- and inter-day accuracy and precision were below 15 % for all analytes. Apparent extraction recoveries were above 97 %, and ion suppression rates were between 4 and 53 %. Mean BA level in serum/plasma from healthy volunteers ranged from 11 +/- 4 nM (tauroursodeoxycholic acid) to 1321 +/- 1442 nM (glycochenodeoxycholic acid). As a proof of concept, the assay was applied to plasma samples derived from a clinical phase I study of myrcludex B, a novel first-in-class virus entry inhibitor for the treatment of chronic hepatitis B and D. The results demonstrate that myrcludex-induced inhibition of the hepatic BA transporter Na(+)-taurocholate cotransporting polypeptide (NTCP) significantly affects plasma BA level. These observations provide novel insights into drug-induced metabolic responses and will be indispensable for the assessment of side effects and dose-finding processes during future clinical trials. PMID- 26143063 TI - Ultrasensitive microfluidic array for serum pro-inflammatory cytokines and C reactive protein to assess oral mucositis risk in cancer patients. AB - In addition to disease diagnostics, there is a need for biomarkers to predict severity of cancer therapy side effects such as oral mucositis. Oral mucositis is an inflammatory lesion of oral mucosa caused by high-dose chemotherapy and/or radiation that is especially prevalent during oral cancer treatment. We describe here a semi-automated, modular microfluidic immunoarray optimized for ultrasensitive detection of pro-inflammatory cytokines involved in pathobiology of oral mucositis. Our goal is to methodologically identify risk of mucositis early in oral cancer treatment, before the onset of lesions. Biomarkers include tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and C-reactive protein (CRP). Protein analytes were captured from serum in a capture chamber by 1-MUm magnetic beads coated with antibodies and enzyme labels. Beads are then transported downstream to a detection chamber containing an eight-sensor array coated with glutathione-coated gold nanoparticles (GSH-AuNP) and a second set of antibodies to capture the beads with analyte proteins. In this first application of the immunoarray to four-protein multiplexed measurements, ultralow detection limits of 10-40 fg mL(-1) in 5 MUL serum were achieved for simultaneous detection in 30 min. Mass detection limits were 2.5-10 zmol, as few as 1500 molecules. Accuracy and diagnostic utility of the arrays were demonstrated by correlation of levels of the four biomarker proteins in serum from head and neck cancer patients with results from standard ELISA. This approach may lead to rapid, low-cost estimates of projected risk for severity of oral mucositis in cancer patients to enable improved therapeutic management. PMID- 26143064 TI - Genetic analysis of seedling resistance to crown rust in five diploid oat (Avena strigosa) accessions. AB - Crown rust, caused by Puccinia coronata Corda f. sp. avenae Eriks., is a serious menace in oats, for which resistance is an effective means of control. Wild diploid oat accessions are a source of novel resistances that first need to be characterised prior to introgression into locally adapted oat cultivars. A genetic analysis of resistance to crown rust was carried out in three diverse diploid oat accessions (CIav6956, CIav9020, PI292226) and two cultivars (Saia and Glabrota) of A. strigosa. A single major gene conditioning resistance to Australian crown rust pathotype (Pt) 0000-2 was identified in each of the three accessions. Allelism tests suggested that these genes are either the same, allelic, or tightly linked with less than 1 % recombination. Similarly, a single gene was identified in Glabrota, and possibly two genes in Saia; both cultivars previously reported to carry two and three crown rust resistance genes, respectively. The identified seedling resistance genes could be deployed in combination with other resistance gene(s) to enhance durability of resistance to crown rust in hexaploid oat. Current diploid and hexaploid linkage maps and molecular anchor markers (simple sequence repeat [SSR] and diversity array technology [DArT] markers) should facilitate their mapping and introgression into hexaploid oat. PMID- 26143065 TI - Impact of haze-fog days to radon progeny equilibrium factor and discussion of related factors. AB - The equilibrium factor F between radon and its short-lived progenies is an important parameter to estimate radon exposure of humans. Therefore, indoor and outdoor concentrations of radon and its short-lived radon progeny were measured in Beijing area using a continuously measuring device, in an effort to obtain information on the F value. The results showed that the mean values of F were 0.58 +/- 0.13 (0.25-0.95, n = 305) and 0.52 +/- 0.12 (0.31-0.91, n = 64) for indoor and outdoor, respectively. The indoor F value during haze-fog days was higher than the typical value of 0.4 recommended by the United Nations Scientific Committee on the Effects of Atomic Radiation, and it was also higher than the values of 0.47 and 0.49 reported in the literature. A positive correlation was observed between indoor F values and PM2.5 concentrations (R (2) = 0.71). Since 2013, owing to frequent heavy haze-fog events in Beijing and surrounding areas, the number of the days with severe pollution remains at a high level. Future studies on the impact of the ambient fine particulate matter on indoor radon progeny equilibrium factor F could be important. PMID- 26143066 TI - Somatic Mutation of ARHI Gene in Hepatocellular Carcinomas. PMID- 26143068 TI - Models of care choices in today's nursing workplace: where does team nursing sit? AB - This paper provides an overview of the developmental history of models of care (MOC) in nursing since Florence Nightingale introduced nurse training programs in a drive to make nursing a discipline-based career option. The four principal choices of models of nursing care delivery (primary nursing, individual patient allocation, team nursing and functional nursing) are outlined and discussed, and recent MOC literature reviewed. The paper suggests that, given the ways work is being rapidly reconfigured in healthcare services and the pressures on the nursing workforce projected into the future, team nursing seems to offer the best solutions. PMID- 26143067 TI - Impact of Dose Reductions, Delays Between Chemotherapy Cycles, and/or Shorter Courses of Adjuvant Chemotherapy in Stage II and III Colorectal Cancer Patients: a Single-Center Retrospective Study. AB - PURPOSE: Most stage II or III colorectal cancer patients are receiving nowadays a 4 to 6-month course of adjuvant chemotherapy. However, delays between cycles, reductions in the doses of chemotherapy drugs, or even permanent omissions of chemotherapy cycles might take place due to side effects or patient's preference. We examined the impact of these treatment modifications on recurrence-free survival (RFS) and overall survival (OS). METHODS: We retrospectively collected data from colorectal cancer patients who had received adjuvant chemotherapy in our Department. Patients were categorized in five groups based on whether they had or not delays between chemotherapy cycles, dose reductions, and permanent omissions of chemotherapy cycles. Three-year RFS and OS of the five different groups were compared using the log-rank test and the Sidak approach. RESULTS: Five hundred and eight patients received treatment. Twenty seven percent of the patients had the full course of chemotherapy; the others had delays, dose reductions, or early termination of the treatment. No statistically significant differences were observed in 3-year RFS and OS between the five groups. A trend for worse RFS was noticed with early termination of treatment. A similar trend was also noticed for OS but only for stage II patients. CONCLUSION: In colorectal cancer patients, receiving adjuvant chemotherapy, delays between chemotherapy cycles, dose reductions of chemotherapy drugs, or even early termination of the treatment course do not seem to have a negative impact in 3-year RFS and OS; however, due to the trend of worse RFS in patients receiving shorter courses of chemotherapy, further studies are needed. PMID- 26143069 TI - Backbone structure of Yersinia pestis Ail determined in micelles by NMR restrained simulated annealing with implicit membrane solvation. AB - The outer membrane protein Ail (attachment invasion locus) is a virulence factor of Yersinia pestis that mediates cell invasion, cell attachment and complement resistance. Here we describe its three-dimensional backbone structure determined in decyl-phosphocholine (DePC) micelles by NMR spectroscopy. The NMR structure was calculated using the membrane function of the implicit solvation potential, eefxPot, which we have developed to facilitate NMR structure calculations in a physically realistic environment. We show that the eefxPot force field guides the protein towards its native fold. The resulting structures provide information about the membrane-embedded global position of Ail, and have higher accuracy, higher precision and improved conformational properties, compared to the structures calculated with the standard repulsive potential. PMID- 26143070 TI - High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease. AB - BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis. PMID- 26143071 TI - Public health policy and walking in England-analysis of the 2008 'policy window'. AB - BACKGROUND: Although the government in England has a long-standing interest in walking promotion, this has not been accompanied by a coherent strategic plan or investment to support physical activity behaviour change. However, in 2008 the government announced its intention to invest L7 million into walking promotion. This article utilises Kingdon's Multiple Streams framework as an organising principle through which to interrogate the reasons behind the increased emphasis on walking promotion as part of the public health policy agenda in England. METHODS: The research adopted a case study design. Data were obtained through document analysis of relevant policies and semi-structured interviews with experts in the walking sector, including both government and non-government representatives. RESULTS: Kingdon's Multiple Streams theory proposes that at certain points in time, 'policy windows' are created through the convergence of a problem, an appropriate solution, and a receptive political environment, and this policy window presents an opportunity for major policy change. The findings of this research suggest that the success of London in securing the 2012 Olympic and Paralympic Games was the primary trigger in the creation of a policy window for walking promotion in recent years. CONCLUSIONS: Despite previous interest in walking promotion from the health and transport sectors, it was the recent alignment with the sports agenda that led to increased political commitment. This raises concerns that the research evidence on the health benefits of physical activity and rising levels of inactivity in England, are insufficient to secure government support and investment, and that multi-sector lobbying and joined-up political action may be critical in advancing this agenda. PMID- 26143073 TI - Two-port totally extraperitoneal inguinal hernia repair: a 10-year experience. AB - PURPOSE: To evaluate the feasibility, safety, and long-term outcomes of laparoscopic two-port totally extraperitoneal (TEP) inguinal hernia repair. METHODS: A 10-year retrospective analysis from 2004 to 2013 of patients undergoing two-port TEP performed by a single surgeon at three surgical centers. RESULTS: 336 consecutive patients underwent two-port TEP repairing 478 hernias. 315 (93.8 %) patients were male and 21 (6.2 %) were female. Mean age +/- SD was 47 +/- 14 years and mean body mass index +/- SD was 28.0 +/- 4.7 kg/m(2). Indications for surgery included primary repair 303 (90.2 %), recurrence from open repair 28 (8.3 %), and incarcerated inguinal hernia 5 (1.5 %). 194 (57.7 %) cases were unilateral and 142 (42.3 %) were bilateral. Operative time +/- SD was 38.7 +/- 14.9 min for unilateral repair and 43.4 +/- 17.6 min for bilateral repair. Two-port TEP was successful in 316 (94.0 %). 20 (6.0 %) cases required the addition of a third port. 2 (0.6 %) cases were converted to open repair. Mean follow-up time +/- SD was 5.4 +/- 2.7 years. Postoperative complications included urinary retention 5 (1.5 %), seroma 7 (2.1 %), hematoma 1 (0.3 %), surgical site infection 4 (1.2 %), and chronic inguinal pain 3 (0.9 %). 11 (2.3 %) hernias recurred. CONCLUSION: Two-port TEP appears to be a feasible, safe, and effective method for laparoscopic inguinal hernia repair and should be considered a viable, less invasive alternative to conventional three-port techniques. PMID- 26143074 TI - Low-dose radiation cancer susceptibility models. PMID- 26143072 TI - Proper mesh overlap is a key determinant in hernia recurrence following laparoscopic ventral and incisional hernia repair. AB - BACKGROUND: Ventral hernia can be repaired through either an open or laparoscopic approach. A major problem following hernia repair is recurrence, and the technique used for hernia repair influences the rate of hernia recurrence. Data from individual studies show that the area of mesh overlap used during hernia repair correlates with hernia recurrence, but no meta-analyses have previously been published. The aim of this review was to perform a meta-analysis to determine if the area of mesh overlap correlates with the rate of hernia recurrence after ventral and incisional hernia repair. METHODS: Studies from 1990 to 2013 that used a mesh in open or laparoscopic procedures, and that reported both the area of mesh overlap beyond the fascial defect and the recurrence rate, were assessed for inclusion in the final analysis. A pooled estimation of combined overall risk was calculated according to a random effect model. RESULTS: A total of 95 articles, with 111 study populations, met all criteria and were included in the final analysis. For open procedures, results showed no correlation between the pooled estimation of risk for recurrence of ventral hernia and area of mesh overlap used for hernia repair (<3 cm, incidence rate 0.065; 3-5 cm, incidence rate 0.070; >5 cm, incidence rate 0.060). In laparoscopic procedures, the pooled estimation of risk for recurrence of hernia decreased with increasing area of mesh overlap (<3 cm, incidence rate 0.086; 3-5 cm, incidence rate 0.046; >5 cm, incidence rate 0.014). CONCLUSION: Risk of hernia recurrence decreases with increasing area of mesh overlap in laparoscopic, but not open, procedures for ventral hernia repair. PMID- 26143075 TI - "Choosing Life": Birth Mothers on Abortion and Reproductive Choice. AB - PURPOSE: As the least-chosen option when faced with an unplanned pregnancy, adoption remains largely unexamined as a reproductive choice. Although the anti abortion movement promotes adoption as its preferred alternative to abortion, little is known of birth mothers' pregnancy decision making and whether adoption was chosen in lieu of abortion. METHODS: I conducted in-depth interviews with 40 women who had placed infants for adoption from 1962 to 2009. Participants were asked about all aspects of their adoption experiences, including their pregnancy decision making and thoughts on abortion. Interview transcripts were analyzed using grounded theory to find unifying themes speaking to reproductive choice. RESULTS: Participants' stories revealed widely varying ideas about abortion. Many were opposed to abortion, but a greater number supported abortion as a reproductive choice, although one they did not choose for themselves. Birth mothers were most often choosing between adoption and parenting, not adoption and abortion. Most participants would have preferred to parent, but did not because of external variables. Mixed experiences with adoption also influenced participants' long-term ideas about reproductive choice. CONCLUSION: Findings suggest that the anti-abortion framing of adoption as a preferable alternative to abortion is inconsistent with birth mothers' pregnancy decision-making experiences and their feelings about adoption. Reducing social barriers to both abortion and parenting will ensure that adoption is situated as a true reproductive choice. PMID- 26143076 TI - Examining Life-Course Socioeconomic Position, Contextualized Stress, and Depression among Well-Educated African-American Pregnant Women. AB - PURPOSE: This article explores how childhood and adulthood socioeconomic position (SEP) and socioeconomic mobility, as indicators of life-course experiences, impact the relationship between contextualized stress and depression among well educated, pregnant African-American women. METHODS: The Jackson, Hogue, Phillips Contextualized Stress Measure and the Beck Depression Inventory were administered to 101 well-educated, pregnant African-American women during their first and second trimesters. Bivariate associations and regression analysis were conducted to assess life-course SEP, mobility, and contextualized stress as predictors of depression. Based on the demographic data for childhood and adult SES, the SEP and mobility variables were created. RESULTS: Results from chi2 analysis revealed that high contextual stress was significantly associated with no change in mobility, that is, staying the same. Results from regression models found that contextualized stress was the only predictor for depression. Additionally, life course SEP and mobility did not moderate the relationship between contextualized stress and depression. CONCLUSIONS: Our findings illuminated the persistence of racial and gendered stress as risk factors for depression among well-educated, pregnant African-American women, regardless of life-course SEP. We offer an explanation as to why African-American women who possess the material and social resources thought to mediate psychosocial and pregnancy risks remain in jeopardy. PMID- 26143077 TI - More than meets the eye: Using cognitive work analysis to identify design requirements for future rail level crossing systems. AB - An increasing intensity of operations means that the longstanding safety issue of rail level crossings is likely to become worse in the transport systems of the future. It has been suggested that the failure to prevent collisions may be, in part, due to a lack of systems thinking during design, crash analysis, and countermeasure development. This paper presents a systems analysis of current active rail level crossing systems in Victoria, Australia that was undertaken to identify design requirements to improve safety in future rail level crossing environments. Cognitive work analysis was used to analyse rail level crossing systems using data derived from a range of activities. Overall the analysis identified a range of instances where modification or redesign in line with systems thinking could potentially improve behaviour and safety. A notable finding is that there are opportunities for redesign outside of the physical rail level crossing infrastructure, including improved data systems, in-vehicle warnings and modifications to design processes, standards and guidelines. The implications for future rail level crossing systems are discussed. PMID- 26143078 TI - The quantitative assessment of the pre- and postoperative craniosynostosis using the methods of image analysis. AB - This paper considers the problem of the CT based quantitative assessment of the craniosynostosis before and after the surgery. First, fast and efficient brain segmentation approach is proposed. The algorithm is robust to discontinuity of skull. As a result it can be applied both in pre- and post-operative cases. Additionally, image processing and analysis algorithms are proposed for describing the disease based on CT scans. The proposed algorithms automate determination of the standard linear indices used for assessment of the craniosynostosis (i.e. cephalic index CI and head circumference HC) and allow for planar and volumetric analysis which so far have not been reported. Results of applying the introduced methods to sample craniosynostotic cases before and after the surgery are presented and discussed. The results show that the proposed brain segmentation algorithm is characterized by high accuracy when applied both in the pre- and postoperative craniosynostosis, while the introduced planar and volumetric indices for the disease description may be helpful to distinguish between the types of the disease. PMID- 26143079 TI - Cloning and characterization of a novel caspase-8-like gene in Crassostrea gigas. AB - Cysteine-dependent aspartate-directed proteases, or caspases, play key roles in apoptosis and immune defense. In this study, we cloned the first caspase-8-like gene (CgCaspase8-2) identified in the pacific oyster, Crassostrea gigas. The 2572 bp cDNA encodes a putative protein of 714 amino acids that contains two tandem death effector domains (DEDs) at the N-terminal, and P20 and P10 domains at the C terminal. The conserved pentapeptide motif QACQG was also identified in the deduced CgCaspase8-2 protein. Phylogenetic analysis indicated that CgCaspase8-2 was clustered with initiator caspases in the invertebrate subgroup, but the similarity between CgCaspase8-2 and other invertebrate caspase-8s was low. CgCaspase8-2 protein was localized in the cytoplasm, and over-expression of CgCaspase8-2 in HEK293T cells induced cell death, suggesting a role in apoptosis. Quantitative real-time PCR results demonstrated that CgCaspase8-2 was widely expressed in various tissues and developmental stages, with the highest CgCaspase8-2 expression levels detected in hemolymph and the blastula stage. Furthermore, CgCaspase8-2 transcripts showed no change in response to a bacterial challenge but exhibited notable up-regulation post-poly (I:C) challenge, suggesting that CgCaspase8-2 is specifically involved in immune responses against viruses. In summary, CgCaspase8-2 is involved in both apoptotic and immune function. PMID- 26143080 TI - Hydrometallurgical recovery of heavy metals from low grade automobile shredder residue (ASR): An application of advanced Fenton process (AFP). AB - To investigate the leaching and recovery of heavy metals from low-grade automobile shredder residue (ASR), the effects of nitric acid (HNO3) and hydrogen peroxide (H2O2) concentrations, liquid/solid (L/S) ratio, leaching temperature and ASR particle size fractions on the heavy metal leaching rate were determined. The heavy metals were recovered by fractional precipitation and advanced Fenton process (AFP) at different pHs. The toxicity characteristic leaching procedure (TCLP) test was also performed in the residue remaining after heavy metal leaching to evaluate the potential toxicity of ASR. The heavy metal leaching efficiency was increased with increasing HNO3 and H2O2 concentrations, L/S ratio and temperature. The heavy metal leaching efficiencies were maximized in the lowest ASR size fraction at 303 K and L/S ratio of 100 mL/g. The kinetic study showed that the metal leaching was best represented by a second-order reaction model, with a value of R(2) > 0.99 for all selected heavy metals. The determined activation energy (kJ/mol) was 21.61, 17.10, 12.15, 34.50, 13.07 and 11.45 for Zn, Fe, Ni, Pb, Cd and Cr, respectively. In the final residue, the concentrations of Cd, Cr and Pb were under their threshold limits in all ASR size fractions. Hydrometallurgical metal recovery was greatly increased by AFP up to 99.96% for Zn, 99.97% for Fe, 95.62% for Ni, 99.62% for Pb, 94.11% for Cd and 96.79% for Cr. AFP is highly recommended for the recovery of leached metals from solution even at low concentrations. PMID- 26143081 TI - Effective removal of nemacide fosthiazate from an aqueous solution using zero valent iron. AB - In this study, the removal of fosthiazate in an aqueous solution using zero valent iron (ZVI) and the related removal reaction mechanism were investigated. The results indicate that the dissipation of fosthiazate adheres to a pseudo first order reaction law. The apparent rate constant of fosthiazate removal could be improved by increasing the ZVI dosage, control temperature and initial pH. The observed pseudo-first-order degradation rate constants (Kobs) of fosthiazate removal using ZVI were varied in the different electrolyte solutions, and were determined as follows: Kobs (MgSO4) < Kobs (KCl) < Kobs (Control) 0.05). 71.3 % males and 72.9 % females achieved the minimal clinically important change score (MCIC; 2.2 point reduction) for the COMI. Controlling for potential cofounders (preoperative COMI, ASA, complications, pathology), gender showed no significant association with the failure to achieve MCIC. CONCLUSIONS: This results show that women do not differ significantly from men regarding their postoperative outcome, even though they present with a worse preoperative status. The management of a patient's condition should not differ depending on their gender, since both men and women are able to improve to a similar extent. PMID- 26143124 TI - Adaptation and validation of Spanish version of the pediatric Voice Handicap Index (P-VHI). AB - OBJECTIVES: The voice in childhood is a communication tool and a form of emotional expression. It is estimated that 6 to 23% of children may have voice disorders. There is a test, the Pediatric Voice Handicap Index (P-VHI), validated in English to assess the specific impact on quality of life of children with speech pathology. Spanish is the second most widely used language in the world in terms of number of speakers, with over 500 million native speakers, so it is necessary to have tools that allow us to evaluate the effects of dysphonia in Spanish-speaking children. The aim of our study is the validation of the Spanish version of the P-VHI. MATERIAL AND METHODS: We performed a cross-sectional study including patients between 4 and 15 years of age. The English P-VHI validated version was translated into Spanish and this translation was reviewed and modified by three specialists in Otorhinolaryngology. There were two study groups, children who had dysphonia (n=44) and a control group of children without alterations in voice (n=44). The questionnaire was always answered by parents. RESULTS: Significant differences were found between the group of children with dysphonia and the control group in the overall P-VHI score and the different subscales (p<0.001). Optimal internal consistency with a good Cronbach's alpha (alpha=0.81) was found, with high test-retest reliability (Wilcoxon z: -0847, p>0.05). CONCLUSIONS: The Spanish version of the P-VHI is a validated tool that has good internal consistency. It is a reliable test that evaluates the Voice Handicap Index in the pediatric population, with easy application for daily clinical practice. PMID- 26143125 TI - The uncomfortable reality ... We simply do not know if general anesthesia negatively impacts the neurocognitive development of our small children. AB - Annually in the United States more than one million children under the age of 5 years are exposed to anesthetics for therapeutic and diagnostic procedures. Pre clinical data in animal models has consistently shown that anesthetic exposure to the developing brain results in long-term cognitive deficits. Current clinical data addressing the safety of these pharmaceutical agents on the developing human brain is limited. Recently, there has been an enormous amount of attention directed at this potential public health issue in both pre-clinical investigations and ongoing human research. A number of these studies should add to our understanding about the impact anesthetic exposure will have on the developing human brain. Until then, there is little data that absolutely reassures clinicians and parents that the pharmaceutical agents used are indeed safe for our children. The uncomfortable reality is that despite the fact that there are more than one million children younger than 5 years old who receive general anesthesia in the United States annually, and thousands more who are deeply sedated for imaging and diagnostic studies or as a necessary adjunct to care in the intensive care unit, there is little data that assures clinicians and parents that the pharmaceutical agents used are indeed safe for the developing brain. That said, there are no convincing human data to suggest that they are not. PMID- 26143126 TI - Bilateral vocal cord paralysis and hypothyroidism as presenting symptoms of Williams-Beuren syndrome: a case report. AB - Williams-Beuren syndrome is a rare neurodevelopmental disorder caused by deletion of 1.5-1.8Mb genes on chromosome 7q11.23. The syndrome was first described as a triad of supra-valvular aortic stenosis, mental retardation, and distinctive facial features. Our patient was referred due to audible inspiratory stridor when he was seven days old. Following endoscopy he was diagnosed with bilateral vocal cord paralysis and was eventually intubated due to respiratory de-compensation followed by tracheotomy. On further workup he was diagnosed with hypothyroidism. Genetic workup supported the diagnosis of Williams-Beuren syndrome. We report here a case with an unusual clinical presentation. PMID- 26143127 TI - Adaptation and validation of the Malayalam pediatric voice handicap index. AB - OBJECTIVES: The aim of the present study was to adapt and validate the English version of pediatric voice handicap index (pVHI) into Malayalam language. METHODS: The English version of pediatric voice handicap index was translated into Malayalam language using parallel back translation. The translated version was content validated by three qualified speech language pathologists. The content familiarity was carried out by 10 parents of children with voice problems. This was distributed to 136 parents (57 parents of children with dysphonia, 79 parents of children with no voice problems). The internal consistency and test--retest reliability was determined using Cronbach's alpha and intraclass correlation coefficient. Independent sample t-test was used to assess the difference in means. Kappa coefficient was used to determine the correlation between overall severity of the problem and total pVHI. Discriminant analysis was used to identify thresholds for differentiating between normal and dysphonic participants. RESULTS: The results obtained revealed that the Malayalam version of pVHI has an excellent internal consistency; total (alpha=0.974), functional (alpha=0.922), physical (alpha=0.953), and emotional (alpha=0.923). There was an excellent test-retest reliability; total (r=0.937), functional (r=0.954), physical (r=0.95), and emotional (r=0.929). The prediction probability of the dysphonics is 98.2% using the discriminant score function. CONCLUSIONS: The translated and validated pVHI tool can be effectively used in the assessment of children with voice problems. It can provide a better insight into the parents' perception of their child's voice problems. PMID- 26143128 TI - The clinical significance and reliability of self-reported smoking status in patients with intracranial aneurysms: a review. AB - OBJECTIVE: Here we present a review of the pathophysiology of tobacco smoking on intracranial aneurysms, self-reported smoking status in these patients, screening tools and assays available for assessing active nicotine use, means of impacting smoking cessation rates, and the potential impact of smoking cessation on risk of rupture and recurrence of treated intracranial aneurysms. METHODS: A literature search using PubMed was done to identify all English language studies relating to tobacco use and intracranial aneurysms, smoking and subarachnoid hemorrhage, nicotine breakdown products, and smoking cessation in neurosurgery. Results from the studies were reviewed and summarized. RESULTS: Tobacco use is an independent risk factor for formation, growth, and rupture of intracranial aneurysms. The pathogenesis of aneurysm formation is complex, and related to increased wall shear stress, endothelial dysfunction, atherosclerosis, and altered gene regulation. Furthermore 80% of all aneurysmal ruptures occur in patients who have used tobacco products. It is suboptimal to rely on self-reported smoking status in order to determine patient risk. Use of objective metrics for ongoing tobacco use may be indicated in selected patients, and may increase smoking cessation rates in these patients. A variety of laboratory and point-of-care tests are available for measurement of nicotine and nicotine breakdown products. Most assays in clinical practice measure the nicotine breakdown product cotinine, which constitutes 75% of nicotine metabolites excreted in the urine and has a substantial half-life of 16h, compared to nicotine's 2-h half-life. With proper identification, an astute physician may be able to assist in smoking cessation and foster improved patient care. By following recommended guidelines and prescribing pharmaceutical aid, a patient has a 2.5 times greater chance of smoking cessation compared with attempting to stop without physician assistance. CONCLUSIONS: Smoking increases risk for intracranial aneurysm formation, rupture, re-rupture and need for re-treatment. Measurement of nicotine breakdown products may have clinical utility in the management of patients with intracranial aneurysms. Smoking cessation interventions may be effective, and use of established smoking cessation tools use may lead to improved clinical outcomes in these patients. The effects of smoking cessation efforts on smoking cessation and intracranial aneurysm outcomes is a fertile field for future investigation. PMID- 26143129 TI - Treatment of selected syringomyelias with syringo-pleural shunt: the experience with a consecutive 26 cases. AB - OF BACKGROUND DATA: It is well established that syringomyelia can cause neurological symptoms and deficit by accumulation of fluid within syrinx cavities that lead to internal compression within the spinal cord. When other intervention treating the underlying etiology failed to yield any improvement, the next option would be a procedure to divert the fluid from the syrinx cavity, such as syringo subarachnoid, syringo-peritoneal or syringo-pleural shunting. The indications and long term efficacy of these direct shunting procedures are still questionable and controversial. OBJECTIVE: To investigate the clinical indication, outcome and complication of syringe-pleural shunt (SPS) as an alternative for treatment of syringomyelia. STUDY DESIGN: We reported a retrospective 26 cases of syringomyelia were found to have indication for a diversion procedure. SPS was offered. Patients' symptoms, mJOA score, and MRI were collected to evaluate the change of the syringomyelia and prognosis of the patients. 2-tailed wilcoxon signed-rank test was used to perform the statistical analysis of the mJOA scores. METHODS: All 26 patients underwent SPS. The clinical information was collected, the mean follow-up time was 27.4 months, 2-tailed wilcoxon signed-rank test was used to perform the statistical analysis of the mJOA scores. The key surgical technique, outcome and complications of SPS were reported in detail. RESULTS: No mortality and severe complications occurred. Postoperative MRIs revealed near complete resolution of syrinx in 14 patients, significant shrinkage of syrinx in 10 patients, no obvious reduction or unchanged in remaining 2 patient. Postoperatively, the symptoms improved in 24 cases (92.3%). Statistical analysis of the mJOA scores showed a statistical significance (P<0.001) between the preoperative group and the 2-week postoperative group. No further significant improvement between 2 weeks to the final follow up at 27 months. CONCLUSION: Collapse or remarkable shrinkage of the syrinx by SPS could ameliorate or at least stabilize the symptoms for the patient. We recommend small laminectomy and a less than 3mm myelotomy either at PML or DREZ. The SPS procedure can be an effective and relatively long-lived treatment for the idiopathic syringomyelia and those that failed other options. PMID- 26143130 TI - Microsurgical efficacy and safety of a right-hemispheric approach for unruptured anterior communicating artery aneurysms. AB - OBJECTIVE: We investigated the effectiveness of a right hemispheric surgical approach in treating unruptured anterior communicating artery aneurysms. METHODS: Between January 2005 and June 2012, 305 patients with anterior communicating artery (Acom) aneurysms were treated using the pterional approach. Among them, 113 who underwent microsurgery with an unruptured Acom aneurysm were enrolled in this study. Every patient was evaluated with digital subtraction angiography preoperatively and CT scans were taken several times postoperatively. Surgical outcomes and complications were evaluated at discharge using the Glasgow Outcome Scale and at 6 months after surgery with CT angiography. RESULTS: Enrolled patients included 55 males and 58 females with a mean age of 56.3 years (range: 30-75 years). The mean diameter of the aneurysm was 5.8mm (range: 1.9-24.1). Left A1 dominancy was found in 71 patients (62.8%) whereas right A1 dominancy was found in 20 patients (17.7%), and right pterional craniotomies were performed in 92 patients (81.4%) while left pterional craniotomies were performed in 21 patients (18.6%). Complete clip application was achieved in 94.9% of patients (74 of 78) in right-side approach group but in only 81.3% of patients (13 of 16) in left-side approach group. Despite a left A1 dominancy and approached from the right, more than 90% of the patients had an excellent outcome at discharge (GOS 5) and more than 90% a complete aneurysm clipping at the 6-month follow-up CT angiography although it was not statistically significant. CONCLUSION: Microsurgical clipping of the unruptured Acom aneurysm through a right-side surgical approach showed favorable postoperative clinical and anatomical outcomes, especially aneurysms smaller than 10mm. PMID- 26143131 TI - The Role of Community Pharmacies in Respiratory Disease Control. PMID- 26143132 TI - Pneumothorax and Congenital Diaphragmatic Hernia: An Unusual Combination. PMID- 26143133 TI - Prognostic Factors in Stage I Lung Cancer. PMID- 26143134 TI - First Argentine study on alpha-1 antitrypsin deficiency in dried blood spot samples from COPD patients. PMID- 26143135 TI - Paraneoplastic acquired ichthyosis in lung cancer. PMID- 26143136 TI - Prevalence of human respiratory syncytial virus circulating in Iran. AB - Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection during early childhood and is associated with a great burden on patients, parents, and society. While no treatment is yet available, results from recent phase 2 clinical trials of cell-entry inhibitors and RSV vaccines are promising. To prepare for introduction of these novel therapeutics, good understanding of its molecular epidemiology and continuous RSV surveillance data are necessary. This paper provides an overview of RSV prevalence and genotype distribution in Iran from 1996 to 2013. This meta-analysis includes 21 published studies. In total, 775 (18.7%) of 4140 respiratory specimens were positive for RSV infection. The male-female ratio of RSV-positive patients was 1.5:1. Significant peaks of RSV infection were detected during the cold season (November March). RSV infection was mainly observed in patients <2 years of age. Phylogenetic studies showed that genotypes GA1, GA2, GA5, and BA co-circulated in Iran in 2007-2013. This review highlights the necessity of introducing standard molecular surveillance programs to inform the epidemiological, clinical, and pathological characteristics of various RSV genotypes. Improved understanding of the molecular epidemiology will be useful for development of novel RSV therapeutics. PMID- 26143137 TI - Influence of Sokal, Hasford, EUTOS scores and pharmacogenetic factors on the complete cytogenetic response at 1 year in chronic myeloid leukemia patients treated with imatinib. AB - Imatinib mesylate is currently considered the first-line treatment for chronic myeloid leukemia (CML). Sokal, Hasford and EUTOS are the three major risk categorization scores available for CML patients. The present study aimed to explore the influence of three risk score, genetic polymorphisms of ABCB1, OCT1, ABCG2 and trough level concentration on complete cytogenetic response at 1 year and overall survival. The mean time period of follow-up was 53.05 months, and the overall survival was 94.6%. The Sokal score (P 0.014), Hasford score (P 0.016) and MDR1 C3435T (P 0.001) tend to influence the overall survival in the patients. The patients who had better overall survival had early complete cytogenetic response (P 0.0003). The ABCG2 C421A was the covariate which had correlation with the complete cytogenetic response. A perceptive approach incorporating pharmacogenetic evaluation with major risk categorization score at the initial stage will help in ensuring better treatment success in CML patients treated with imatinib. PMID- 26143138 TI - Patent Foramen Ovale in Recreational and Professional Divers: An Important and Largely Unrecognized Problem. AB - Patent foramen ovale (PFO) is associated with an increased risk of decompression sickness (DCS) in divers that results from a paradoxical embolization of nitrogen bubbles. The number of scuba divers worldwide is estimated in the millions, and the prevalence of PFO is 25%-30% in adults. It is interesting that despite these numbers, many important issues regarding optimal screening, risk stratification, and management strategy still remain to be resolved. Recently published data suggest the possible effectiveness of both PFO closure and conservative diving measures in preventing arterial gas embolization. This review aims to introduce the basic principles of physiology and the pathophysiology of bubble formation and DCS, summarize the current literature on PFO and diving, and review the possibilities of diagnostic workup and management. PMID- 26143139 TI - A Practical Approach to the Investigation of an rSr' Pattern in Leads V1-V2. AB - The differential diagnosis of an rSr' pattern in leads V1-V2 on electrocardiogram is a frequently encountered entity in clinical cardiology. This finding often presents itself in asymptomatic and healthy individuals. The causes might vary from benign and nonpathological, to severe and life-threatening diseases, such as Brugada syndrome or arrhythmogenic right ventricular dysplasia. Workup of these patients involves a history and physical examination to screen for underlying cardiac disease and potential triggers. Routine investigation involves blood work and a thorough electrocardiographic examination. Echocardiography has a role in evaluating patients in whom structural heart disease is suspected. Pulmonary testing using computed tomography can be conducted if right ventricular enlargement is identified. More advanced testing is not warranted if these initial investigations are reassuring. Referral to an arrhythmia specialist should be considered for patients in whom this finding is due to Brugada syndrome, arrhythmogenic right ventricular dysplasia, or Wolf-Parkinson-White syndrome. We propose a clinical and electrocardiographic algorithm that will assist clinicians in narrowing their differential diagnosis. PMID- 26143140 TI - Cardiovascular Risk Factors and In-hospital Mortality in Acute Coronary Syndromes: Insights From the Canadian Global Registry of Acute Coronary Events. AB - BACKGROUND: There are conflicting data regarding the relationship between the number of modifiable traditional risk factors and prognosis in acute coronary syndromes (ACS). This controversy might in part be explained by the differential use of prehospital medications. METHODS: Using data from the Canadian, multicentre Global Registry of Acute Coronary Events (GRACE) (1999-2008), we stratified 13,686 ACS patients into 3 groups (0, 1-2, vs 3-4 risk factors) and compared their baseline characteristics, in-hospital treatments, and outcomes. Multivariable logistic regressions were performed to adjust for the components of the GRACE risk score and preadmission statin and acetylsalicylic acid (ASA) use. RESULTS: Among these patients (ST-elevation myocardial infarction 28.3%), 14.5%, 62.6%, and 22.9% had 0, 1-2, and 3-4 risk factors, respectively. Patients with fewer risk factors were less likely to be on ASA, statin, and other prehospital medications. Unadjusted in-hospital mortality was significantly different across risk factor groups (4.9%, 3.0%, and 3.1% for 0, 1-2, and 3-4 risk factor groups, respectively, P for trend = 0.002). This difference was no longer significant after adjusting for the components of the GRACE risk score (P for trend = 0.088) and further adjusting for preadmission statin and ASA use (P for trend = 0.96). For in-hospital mortality, there was no significant interaction between risk factor categories and ACS type (P = 0.26). CONCLUSIONS: The lower mortality observed in patients with ACS with more risk factors may be partially attributed to the protective effect of prehospital ASA and statin use. The number of risk factors does not provide incremental prognostic value beyond the validated GRACE risk score. PMID- 26143141 TI - Prognostic Value of Osteoprotegerin in Acute Heart Failure. AB - BACKGROUND: Osteoprotegerin (OPG) is promising as a predictor of adverse prognosis in patients with acute coronary syndromes and chronic heart failure. Its prognostic value in acute heart failure (AHF) is unknown. The aim of this study was to assess the prognostic value provided by serum OPG levels at discharge after an admission for AHF. METHODS: In a prospective study, we enrolled 338 patients consecutively admitted with AHF to the internal medicine department of a tertiary care university hospital in Porto, Portugal between March 2009 and December 2010. OPG was measured using a commercial enzyme-linked immunosorbent assay and was both analyzed as a continuous variable and categorized by quartiles. Patients were followed for up to 6 months after discharge to ascertain the occurrence of all-cause death or hospital readmission resulting from AHF. RESULTS: During follow-up, 119 patients died or were readmitted for AHF. A graded increase in the risk of the combined end point was observed across quartiles of OPG. At 6 months, the cumulative risk of the end point was 25% for the first quartile and 50% for the fourth quartile. The multivariable adjusted risk of death or hospitalization for AHF increased progressively across categories of OPG up to a statistically significant 2.44 fold increase in risk in the highest category (P for linear trend = 0.002, ie, by 5% per 10 pg/mL increase in OPG). CONCLUSIONS: Serum OPG was directly associated with a higher probability of death or readmission for AHF within 6 months, irrespective of other known prognostic markers. This was true both when the ejection fraction was preserved and when it was reduced. PMID- 26143142 TI - "One Problem Became Another": Disclosure of Rape-Related Pregnancy in the Abortion Care Setting. AB - OBJECTIVE: We sought to explore the experiences of women who disclosed that their pregnancies resulted from rape in the abortion care setting, as well as the experiences of professionals involved in care of women with rape-related pregnancy. METHODS: In-depth interviews were conducted with 9 patients who had terminated rape-related pregnancies and 12 professionals working in abortion care or rape crisis advocacy (5 abortion providers, 4 rape crisis center advocates, 2 social workers, and 1 clinic administrator). Transcribed interviews were coded and analyzed for themes related to the experiences of disclosing rape and the consequences of disclosure in the abortion care setting. RESULTS: Patients and professionals involved in care of women with rape-related pregnancy described opportunities arising from disclosure, including interpersonal (explaining abortion decision making in the context of assault, belief, and caring by providers), as well as structural opportunities (funding assistance, legal options, and mental health options). Whereas most patients did not choose to pursue all three structural opportunities, both patients and professionals emphasized the importance of offering them. The most important consequence of disclosure for patients was being believed and feeling that providers cared about them. CONCLUSION: Rape-related pregnancy disclosure in the abortion care setting can lead to opportunities for interpersonal support and open options for funding, legal recourse, and mental health care. Those working in abortion care should create environments conducive to disclosure and opportunities for rape survivors to access these additional options if they desire. PMID- 26143143 TI - Cdk5-mediated mitochondrial fission: A key player in dopaminergic toxicity in Huntington's disease. AB - The molecular mechanisms underlying striatal vulnerability in Huntington's disease (HD) are still unknown. However, growing evidence suggest that mitochondrial dysfunction could play a major role. In searching for a potential link between striatal neurodegeneration and mitochondrial defects we focused on cyclin-dependent kinase 5 (Cdk5). Here, we demonstrate that increased mitochondrial fission in mutant huntingtin striatal cells can be a consequence of Cdk5-mediated alterations in Drp1 subcellular distribution and activity since pharmacological or genetic inhibition of Cdk5 normalizes Drp1 function ameliorating mitochondrial fragmentation. Interestingly, mitochondrial defects in mutant huntingtin striatal cells can be worsened by D1 receptor activation a process also mediated by Cdk5 as down-regulation of Cdk5 activity abrogates the increase in mitochondrial fission, the translocation of Drp1 to the mitochondria and the raise of Drp1 activity induced by dopaminergic stimulation. In sum, we have demonstrated a new role for Cdk5 in HD pathology by mediating dopaminergic neurotoxicity through modulation of Drp1-induced mitochondrial fragmentation, which underscores the relevance for pharmacologic interference of Cdk5 signaling to prevent or ameliorate striatal neurodegeneration in HD. PMID- 26143144 TI - Synergistic induction of insulin resistance by endothelin-1 and cAMP in 3T3-L1 adipocytes. AB - Both endothelin-1 (ET-1) and cAMP are implicated for inducing insulin resistance. Since we have shown previously that there is a crosstalk between ET-1 and cAMP signaling pathways in regulating glucose uptake in 3T3-L1 adipocytes, we extended our investigation in this study on whether they may have a synergistic effect on inducing insulin resistance. Our results showed that it was indeed the case. Insulin-stimulated glucose uptake, phosphorylation of PKB, IRS-1-associated PI3K, and IRS-1 tyrosine phosphorylation were all inhibited by ET-1 and 8-bromo cAMP in a synergistic manner. IRS-1 protein levels were similarly decreased by ET-1 and 8 bromo cAMP, attributable to suppressed mRNA expression. In addition, after correction for the loss in IRS-1 protein, the inhibition of insulin-stimulated IRS-1 tyrosine phosphorylation or IRS-1-associated PI3K was mainly caused by cAMP. Moreover, whereas IRS-2 protein levels were increased by cAMP or ET-1 plus cAMP, insulin-stimulated IRS-2-associated PI3K activities were abolished by both treatments. Furthermore, ET-1 and beta-adrenergic agonists had similar synergistic inhibition on insulin-stimulated glucose uptake. In conclusion, we have shown that ET-1 and cAMP may synergistically induce insulin resistance in adipocytes via inhibiting IRS-1 expression as well as insulin-stimulated IRS 1/IRS-2 activities. PMID- 26143145 TI - Academic performance and perception of learning following a peer coaching teaching and assessment strategy. AB - Peer coaching has been associated with positive effects on learning. Specifically, these associations have been explored in complex healthcare professions. A social theory of learning has been proposed as a key component of the utility of peer coaching. Further, within the peer coaching model, assessment has been considered as an important driver. Empirical support for these dimensions of the model is lacking. To quantify assessment achievements and explore emergent attitudes and beliefs about learning related to a specific peer coaching model with integrated assessment. A longitudinal study based in a UK Higher Education Institute recorded assessment achievements and surveyed attitudes and beliefs in consecutive Year 1 undergraduate (physiotherapy) students (n = 560) between 2002 and 2012. A 6% improvement in academic achievement was demonstrated following the introduction of a peer coaching learning model. This was increased by a further 5% following the implementation of an integrated assessment. The improvement related to an overall averaged increase of one marking band. Students valued the strategy, and themes relating to the importance of social learning emerged from survey data. Peer coaching is an evidence-based teaching and learning strategy which can facilitate learning in complex subject areas. The strategy is underpinned by social learning theory which is supported by emergent student-reported attitudes. PMID- 26143146 TI - Validation of shortened 2-day sterility testing of mesenchymal stem cell-based therapeutic preparation on an automated culture system. AB - Cell therapy products represent a new trend of treatment in the field of immunotherapy and regenerative medicine. Their biological nature and multistep preparation procedure require the application of complex release criteria and quality control. Microbial contamination of cell therapy products is a potential source of morbidity in recipients. The automated blood culture systems are widely used for the detection of microorganisms in cell therapy products. However the standard 2-week cultivation period is too long for some cell-based treatments and alternative methods have to be devised. We tried to verify whether a shortened cultivation of the supernatant from the mesenchymal stem cell (MSC) culture obtained 2 days before the cell harvest could sufficiently detect microbial growth and allow the release of MSC for clinical application. We compared the standard Ph. Eur. cultivation method and the automated blood culture system BACTEC (Becton Dickinson). The time to detection (TTD) and the detection limit were analyzed for three bacterial and two fungal strains. The Staphylococcus aureus and Pseudomonas aeruginosa were recognized within 24 h with both methods (detection limit ~10 CFU). The time required for the detection of Bacillus subtilis was shorter with the automated method (TTD 10.3 vs. 60 h for 10-100 CFU). The BACTEC system reached significantly shorter times to the detection of Candida albicans and Aspergillus brasiliensis growth compared to the classical method (15.5 vs. 48 and 31.5 vs. 48 h, respectively; 10-100 CFU). The positivity was demonstrated within 48 h in all bottles, regardless of the size of the inoculum. This study validated the automated cultivation system as a method able to detect all tested microorganisms within a 48-h period with a detection limit of ~10 CFU. Only in case of B. subtilis, the lowest inoculum (~10 CFU) was not recognized. The 2-day cultivation technique is then capable of confirming the microbiological safety of MSC and allows their timely release for clinical application. PMID- 26143148 TI - Cancer stem cells: a challenging paradigm for designing targeted drug therapies. AB - Despite earlier controversies about their role and existence within tumors, cancer stem cells (CSCs) are now emerging as a plausible target for new drug discovery. Research and development (R&D) efforts are being directed against key gene(s) driving initiation, growth, and metastatic pathways in CSCs and the tumor microenvironment (TME). However, the niche signals that enable these pluripotent CSCs to evade radio- and chemotherapy, and to travel to secondary tissues remain enigmatic. Small-molecule drugs, biologics, miRNA, RNA interference (RNAi), and vaccines, among others, are under active investigation. Here, we examine the feasibility of leveraging current knowhow of the molecular biology of CSCs and their cellular milieu to design futuristic, targeted drugs with potentially lower toxicity that can override the multiple drug-resistance issues currently observed with existing therapeutics. PMID- 26143147 TI - The effects of daily mood and couple interactions on the sleep quality of older adults with chronic pain. AB - We examined the effect of daily negative and positive mood on the sleep quality of knee osteoarthritis (OA) patients (N = 152) and whether a partner's daily responses to a patient's pain behaviors moderated these associations. Patients and their partners completed a baseline interview and 22 daily diary assessments. After controlling for demographic characteristics, OA severity, comorbidities, medication use, relationship satisfaction, and depressed mood, multilevel modeling analyses demonstrated main effects of negative and positive mood on sleep quality indicators. Mood and partner responses interacted such that high solicitous and punishing responses strengthened the association between negative mood and worse sleep. Further, high solicitous responses increased the degree of association between low positive mood and poor sleep, and empathic responses combined with positive mood were associated with better sleep. Results demonstrate that daily negative and positive mood fluctuations can interact with partner responses to affect sleep quality among older adults with chronic pain. PMID- 26143149 TI - Breakdown of deterministic lateral displacement efficiency for non-dilute suspensions: A numerical study. AB - We investigate the effect of particle volume fraction on the efficiency of deterministic lateral displacement (DLD) devices. DLD is a popular passive sorting technique for microfluidic applications. Yet, it has been designed for treating dilute suspensions, and its efficiency for denser samples is not well known. We perform 3D simulations based on the immersed-boundary, lattice Boltzmann and finite-element methods to model the flow of red blood cells (RBCs) in different DLD devices. We quantify the DLD efficiency in terms of appropriate "failure" probabilities and RBC counts in designated device outlets. Our main result is that the displacement mode breaks down upon an increase of RBC volume fraction, while the zigzag mode remains relatively robust. This suggests that the separation of larger particles (such as white blood cells) from a dense RBC background is simpler than separating smaller particles (such as platelets) from the same background. The observed breakdown stems from non-deterministic particle collisions interfering with the designed deterministic nature of DLD devices. Therefore, we postulate that dense suspension effects generally hamper efficient particle separation in devices based on deterministic principles. PMID- 26143150 TI - Design and testing of a high-speed treadmill to measure ground reaction forces at the limit of human gait. AB - Investigations focused on the gait and physiological limits of human speed have been on-going for more than a century. However, due to measurement limitation a kinetic understanding of the foot-ground collision and how these dynamics differ between individuals to confer speed and limit gait has only recently begun to come forth. Therefore, we designed and tested an instrumented high-speed force treadmill to measure the forces occurring at the limits of human performance. The treadmill was designed to maximize flexural stiffness and natural frequency by using a honeycomb sandwich panel as the bed surface and a flexible drive shaft between the drive roller and servo motor to reduce the mass of the supported elements which contribute to the system's response frequency. The functional performance of the force treadmill met or exceeded the measurement criteria established for ideal force plates: high natural frequency (z-axis = 113 Hz), low crosstalk between components of the force (Fx/Fz = 0.0020[SD = 0.0010]; Fy/Fz = 0.0016[SD = 0.0003]), a linear response (R(2) > 0.999) for loading with known weights (range: 44-3857 N), and an accuracy of 2.5[SD = 1.7] mm and 2.8[SD = 1.5] mm in the x and y-axes, respectively, for the point of force application. In dynamic testing at running speeds up to 10 m s(-1), the measured durations and magnitudes of force application were similar between the treadmill and over ground running using a force platform. This design provides a precise instrumented treadmill capable of recording multi-axis ground reaction forces applied during the foot ground contacts of the fastest men and animals known to science. PMID- 26143151 TI - Molecular self-assembly of amphiphilic cyclic phosphoryl gemcitabine with different N-fatty acyl tails and enhanced anticancer effects of the self assembled nanostructures. AB - Molecular self-assembly of nucleosides is important, and the self-assembled nanostructures may be used for drug delivery and targeting. Gemcitabine (GEM) is an important anticancer nucleoside analog though deactivation and multi-drug resistance frequently happen. Four N-fatty acyl derivatives of cyclic phosphoryl GEM were prepared based on the theory of self-assembled drug delivery systems and the HepDirect prodrug technique wherein the prodrug could be degraded by the cytochrome P450 isozymes in hepatocytes to release active drugs. They are cyclic phosphoryl N-octyl gemcitabine (CPOG), cyclic phosphoryl N-dodecanoyl gemcitabine (CPDG), cyclic phosphoryl N-hexadecanoyl gemcitabine (CPHG), and cyclic phosphoryl N-octadecanoyl gemcitabine (CPODG). Their amphiphilicity and self assembling property were explored. The self-assembled nanostructures of them were prepared and simulated. The in vitro anticancer activities of the nanostructures were investigated. The derivatives formed the Langmuir monolayers at the air/water interface, though their surface pressure-molecular area isotherms were different with dependency of the length of lipid chains. The derivatives self assembled into the vesicular or rice-like nanostructures based on the hydrophobic interaction between lipid chains when injected into water, in accordance with the results of computer simulation. The nanostructures showed higher anticancer effects on HepG2 cells than GEM. The nanostructures are promising anticancer nanomedicines. PMID- 26143152 TI - Fabrication of doxorubicin-loaded ellipsoid micelle based on diblock copolymer with a linkage of enzyme-cleavable peptide. AB - In this study, a novel micellar drug carrier was fabricated from an amphiphilic diblock copolymer containing poly (ethylene glycol) monomethyl ether (mPEG) and stearic moiety (C18) with a linkage of valine-citrulline (VC), which can be cleaved by cathepsin B (CB) enriched in lysosome of tumor cell. Moreover, the self-assembled micelles were observed as ellipsoid shape with major and minor axis of ca. 169 and 103nm, respectively. Such drug carrier was used to encapsulate anti-cancer drug doxorubicin (DOX), and hence showed a faster drug release behavior in a mimic lysosome condition containing cathepsin B. It was ascribed to the lysosome-sensitivity of the valine-citrulline linkage, which was verified by the size distribution curve shifted to greater size under the same mimic lysosome condition. Furthermore, in comparison with pristine doxorubicin, the encapsulation strategy of as-fabricated micellar carrier resulted in a predominant decrease of cytotoxicity. On the whole, a micellar drug carrier, which can be disassembled by cathepsin B, has been emerging as a potential of specific drug release in lysosome. Additionally, the controlled nanoscale together with elongated structure of such assembled ellipsoid micelles might contribute passive targeting function to tumor tissue and faster cellular uptake behavior (Zhou et al.). PMID- 26143153 TI - Inclusion body myositis with granuloma formation in muscle tissue. AB - Inclusion body myositis is a form of inflammatory myopathy. We identified 4 cases of inclusion body myositis showing granuloma formation in muscle tissue and aimed to assess the features of this atypical form of inclusion body myositis. We retrospectively reviewed consecutive patients who satisfied European Neuromuscular Centre IBM Research Diagnostic Criteria 2011. Then, we assessed clinical profiles and pathological findings in patients with inclusion body myositis with granuloma and compared these findings with those of typical inclusion body myositis without granuloma. We identified 15 patients with inclusion body myositis. Four patients showed granuloma formation in muscle tissue in addition to typical pathological features of inclusion body myositis. Granulomas comprised a mixture of inflammatory cells, such as macrophages, epithelioid histiocytic cells, and lymphocytes. One patient was found to have mediastinal granulomatous lymphadenopathy; however, the evidence in other patients was insufficient for a diagnosis of systemic sarcoidosis. There were no significant differences between groups with and without granuloma regarding clinical manifestations, laboratory findings, response to immunomodulating therapies, or myopathological profiles. We established a new form of inclusion body myositis showing granuloma formation in muscle tissue. Inclusion body myositis and granuloma formation could have identical pathomechanisms concerning dysregulation of autophagy. PMID- 26143155 TI - Disabled homolog 2 is required for migration and invasion of prostate cancer cells. AB - Disabled homolog 2 (DAB2) is frequently deleted or epigenetically silenced in many human cancer cells. Therefore, DAB2 has always been regarded as a tumor suppressor gene. However, the role of DAB2 in tumor progression and metastasis remains unclear. In this study, DAB2 expression was upregulated along with human prostate cancer (PCa) progression. DAB2 overexpression or knockdown effects in LNCaP and PC3 cell lines were verified to address the biological functions of DAB2 in PCa progression and metastasis. LNCaP and PC3 cell lines were generated from human PCa cells with low and high metastatic potentials, respectively. The results showed that DAB2 shRNA knockdown can inhibit the migratory and invasive abilities of PC3 cells, as well as the tumorigenicity, whereas DAB2 overexpression enhanced LNCaP cell migration and invasion. Further investigation showed that DAB2 regulated the cell migration associated genes in PC3 cells, and the differential DAB2 expression between LNCaP and PC3 cells was partly regulated by histone 4 acetylation. Therefore, DAB2 may play an important role in PCa progression and metastasis. PMID- 26143154 TI - Development of the uncinate fasciculus: Implications for theory and developmental disorders. AB - The uncinate fasciculus (UF) is a long-range white matter tract that connects limbic regions in the temporal lobe to the frontal lobe. The UF is one of the latest developing tracts, and continues maturing into the third decade of life. As such, individual differences in the maturational profile of the UF may serve to explain differences in behavior. Indeed, atypical macrostructure and microstructure of the UF have been reported in numerous studies of individuals with developmental and psychiatric disorders such as social deprivation and maltreatment, autism spectrum disorders, conduct disorder, risk taking, and substance abuse. The present review evaluates what we currently know about the UF's developmental trajectory and reviews the literature relating UF abnormalities to specific disorders. Additionally, we take a dimensional approach and critically examine symptoms and behavioral impairments that have been demonstrated to cluster with UF aberrations, in an effort to relate these impairments to our speculations regarding the functionality of the UF. We suggest that developmental disorders with core problems relating to memory retrieval, reward and valuation computation, and impulsive decision making may be linked to aberrations in uncinate microstructure. PMID- 26143158 TI - CCR5Delta32 mutation and HIV infection: basis for curative HIV therapy. AB - The C-C chemokine receptor 5 (CCR5) is expressed on potential human immunodeficiency virus (HIV) target cells and serves as the predominant co receptor for viral entry during initial transmission and through the early stages of infection. A homozygous Delta32 mutation in the CCR5 gene prevents CCR5 cell surface expression and thus confers resistance to infection with CCR5-tropic HIV strains. Transplantation of hematopoietic stem cells from a CCR5Delta32/Delta32 donor was previously successful in eliminating HIV from the recipient's immune system, suggesting that targeted CCR5 disruption can lead to an HIV cure. Therefore, intense work is currently being carried out on CCR5 gene-editing tools to develop curative HIV therapy. Here, we review the natural function of CCR5, the progress made on CCR5 gene editing to date and discuss the current limitations. PMID- 26143156 TI - Adhesion of bubbles and drops to solid surfaces, and anisotropic surface tensions studied by capillary meniscus dynamometry. AB - Here, we review the principle and applications of two recently developed methods: the capillary meniscus dynamometry (CMD) for measuring the surface tension of bubbles/drops, and the capillary bridge dynamometry (CBD) for quantifying the bubble/drop adhesion to solid surfaces. Both methods are based on a new data analysis protocol, which allows one to decouple the two components of non isotropic surface tension. For an axisymmetric non-fluid interface (e.g. bubble or drop covered by a protein adsorption layer with shear elasticity), the CMD determines the two different components of the anisotropic surface tension, sigmas and sigmaphi, which are acting along the "meridians" and "parallels", and vary throughout the interface. The method uses data for the instantaneous bubble (drop) profile and capillary pressure, but the procedure for data processing is essentially different from that of the conventional drop shape analysis (DSA) method. In the case of bubble or drop pressed against a substrate, which forms a capillary bridge, the CBD method allows one to determine also the capillary bridge force for both isotropic (fluid) and anisotropic (solidified) adsorption layers. The experiments on bubble (drop) detachment from the substrate show the existence of a maximal pulling force, Fmax, that can be resisted by an adherent fluid particle. Fmax can be used to quantify the strength of adhesion of bubbles and drops to solid surfaces. Its value is determined by a competition of attractive transversal tension and repulsive disjoining pressure forces. The greatest Fmax values have been measured for bubbles adherent to glass substrates in pea-protein solutions. The bubble/wall adhesion is lower in solutions containing the protein HFBII hydrophobin, which could be explained with the effect of sandwiched protein aggregates. The applicability of the CBD method to emulsion systems is illustrated by experiments with soybean-oil drops adherent to hydrophilic and hydrophobic substrates in egg yolk solutions. The results reveal how the interfacial rigidity, as well as the bubble/wall and drop/wall adhesion forces, can be quantified and controlled in relation to optimizing the properties of foams and emulsions. PMID- 26143159 TI - Gender and survival after sudden cardiac arrest: A systematic review and meta analysis. AB - BACKGROUND: Conflicting results exist regarding the impact of gender on early survival after sudden cardiac arrest (SCA). We aimed to assess the association between female gender and early SCA survival. METHODS: We searched Embase, MEDLINE, EBM Reviews, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (between 1948 and January 2014) for studies evaluating the association between gender and survival after SCA. Two independent reviewers selected studies of any design or language. Pooled odds ratios (OR) and 95% confidence intervals (CIs) were estimated using a random effects model. Additional sensitivity analyses and meta-regression were carried out to explore heterogeneity. RESULTS: Thirteen studies were included involving 409,323 patients. Women were more likely to present with SCA at home, less likely to have witnessed SCA, had a lower frequency of initial shockable rhythm but were more likely to receive bystander CPR. After adjustment for these differences, women were more likely to survive at hospital discharge (OR 1.1, 95% CI 1.03 1.20, p=0.006, I(2)=61%). This association persisted in multiple sensitivity analyses. CONCLUSION: This meta-analysis of observational studies demonstrates that women have increased odds of survival after SCA. Further studies are needed to address mechanisms explaining this discrepancy. PMID- 26143160 TI - Metal oxide nanoparticles with low toxicity. AB - A number of different nanomaterials produced and incorporated into various products are rising. However, their environmental hazards are frequently unknown. Here we consider three different metal oxide compounds (SnO2, In2O3, and Al2O3), which have not been extensively studied and are expected to have low toxicity. This study aimed to comprehensively characterize the physicochemical properties of these nanomaterials and investigate their toxicity on bacteria (Escherichia coli) under UV illumination and in the dark, as well as on a marine diatom (Skeletonema costatum) under ambient illumination/dark (16-8h) cycles. The material properties responsible for their low toxicity have been identified based on comprehensive experimental characterizations and comparison to a metal oxide exhibiting significant toxicity under illumination (anatase TiO2). The metal oxide materials investigated exhibited significant difference in surface properties and interaction with the living organisms. In order for a material to exhibit significant toxicity, it needs to be able to both form a stable suspension in the culture medium and to interact with the cell walls of the test organism. Our results indicated that the observed low toxicities of the three nanomaterials could be attributed to the limited interaction between the nanoparticles and cell walls of the test organisms. This could occur either due to the lack of significant attachment between nanoparticles and cell walls, or due to their tendency to aggregate in solution. PMID- 26143163 TI - Altering ventilator inspiratory time can reduce autocycling during sleep. PMID- 26143161 TI - Anti-TNF-alpha therapy reduces endothelial cell activation in non-diabetic ankylosing spondylitis patients. AB - Endothelial dysfunction can be detected by the presence of elevated levels of biomarkers of endothelial cell activation. In this study, we aimed to establish whether correlations of these biomarkers with characteristics of patients with ankylosing spondylitis (AS) exist. We also studied the effect of anti-TNF-alpha therapy on these biomarkers. Serum sE-selectin, MCP-1 and sVCAM-1 levels were measured by ELISA in 30 non-diabetic AS patients undergoing anti-TNF-alpha therapy, immediately before and after an infusion of infliximab. Correlations of these biomarkers with clinical features, systemic inflammation, metabolic syndrome and other serum and plasma biomarkers of cardiovascular risk were studied. Potential changes in the concentration of these biomarkers following an infliximab infusion were also assessed. sE-selectin showed a positive correlation with CRP (p = 0.02) and with other endothelial cell activation biomarkers such as sVCAM-1 (p = 0.019) and apelin (p = 0.008). sVCAM-1 negatively correlated with BMI (p = 0.018), diastolic blood pressure (p = 0.008) and serum glucose (p = 0.04). sVCAM-1 also showed a positive correlation with VAS spinal pain (p = 0.014) and apelin (p < 0.001). MCP-1 had a negative correlation with LDL cholesterol (p = 0.026) and ESR (p = 0.017). Patients with hip involvement and synovitis and/or enthesitis in other peripheral joints showed higher levels of MCP-1 (p = 0.004 and 0.02, respectively). A single infliximab infusion led to a significant reduction in sE-selectin (p = 0.0015) and sVCAM-1 (p = 0.04). Endothelial dysfunction correlates with inflammation and metabolic syndrome features in patients with AS. A beneficial effect of the anti-TNF-alpha blockade on endothelial dysfunction, manifested by a reduction in levels of biomarkers of endothelial cell activation, was observed. PMID- 26143162 TI - Relationship between hyperuricemia and dietary risk factors in Chinese adults: a cross-sectional study. AB - Previous studies focusing on identification of dietary risk factors for hyperuricemia reported controversial findings. Moreover, evidence for relationship between hyperuricemia and eating and cooking habits remained scanty. The purpose of this study was to evaluate the associations between hyperuricemia and dietary risk factors. A cross-sectional study was conducted among 1583 participants in a Beijing community. Face-to-face interviews were conducted using questionnaires. Anthropometric measurements and biochemical tests were also performed. The prevalence of hyperuricemia was 14.1 % (20.2 % for males and 7.4 % for females). Among the 1372 subjects included for analysis, 720 (52.5 %) were males and the mean age was 37.7 years. For males, statistically significant associations between hyperuricemia and tea intake, breakfast and midnight snack consumption were found, with an odds ratio of 0.56 (high vs. low), 2.14 (often vs. always) and 0.52 (rarely vs. always), respectively. Smoking, fatty liver disease, triglyceride, low-density lipoprotein cholesterol and fasting blood glucose were significantly related to increased serum uric acid (SUA), with a coefficient of 20.06, 11.52, 7.29, 18.97 and 13.37 on SUA, respectively. For females, no statistically significant associations between hyperuricemia and dietary risk factors were observed. In summary, hyperuricemia is highly prevalent among the adult participants in this Chinese community, especially for men. High tea intake and consuming midnight snack rarely are significantly related to decreased risk of hyperuricemia, while often-eating breakfast is associated with increased risk of hyperuricemia compared with always-eating breakfast in males. Further prospective studies are needed to confirm the findings and to establish dietary recommendations for the prevention and treatment of hyperuricemia. PMID- 26143164 TI - Sleep spindle density increases after continuous positive airway pressure titration in severe obstructive sleep apnea: a preliminary study. PMID- 26143165 TI - Sleep-disordered breathing and cancer incidence: an association for the next decade? PMID- 26143166 TI - Sleep disorders in individuals without sleep apnea increase the risk of peripheral arterial disorder: a nationwide population-based retrospective cohort study. AB - STUDY OBJECTIVES: Previous literature lacks the analysis of non-apnea sleep disorder (NASD) and peripheral arterial disease (PAD). The aim of this study was to evaluate the association between NASD and risk of developing PAD using retrospective data from a national database in Taiwan. DESIGN, SETTING, AND PARTICIPANTS: We identified 46,064 patients with NASD using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD) from 1996 to 2010. We also selected a comparison cohort of 92,128 subjects who were randomly frequency-matched by age, sex, and entry year of the NASD cohort from the same database. INTERVENTIONS: non-apnea sleep disorders. MAIN OUTCOME AND MEASUREMENTS: The study followed up all subjects from their entry date to the occurrence of PAD. We evaluated the risks of PAD using Cox proportional hazards regression models. The survival function for PAD was assessed using the Kaplan-Meier method. RESULTS: The risk of PAD was 1.49-fold in patients with NASD compared with patients without NASD after adjusting for age, sex, and comorbidities. Patients with NASD and diabetes or with NASD and hyperlipidemia had an increased risk of PAD compared to those without NASD and diabetes or hyperlipidemia. CONCLUSIONS: We demonstrated the significantly increased risk of PAD in NASD patients through a nationwide population-based retrospective cohort study. PMID- 26143167 TI - Time-course and molecular mechanism of hepatotoxicity induced by 1,3-dichloro-2 propanol in rats. AB - This study investigated the time-course of 1,3-dichloro-2-propanol (1,3-DCP) induced hepatotoxicity and the molecular mechanism of its oxidative stress and apoptotic changes in rats. Thirty-six male rats were randomly assigned to six groups of six rats each and were administered a single oral dose of 1,3-DCP (90 mg/kg) or its vehicle. 1,3-DCP caused acute hepatic damage, as evidenced by marked increases in serum aminotransferase, alkaline phosphatase, and histopathological alterations. These functional and histopathological changes in the liver peaked at 12h after administration and then decreased progressively. Oxidative stress indices were increased significantly at 6h, peaked at 12h, and then decreased progressively. The number of terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL)- and caspase-3-positive cells increased after 6h, peaked at 12 and 24h, and then decreased. The protein levels of phosphorylated mitogen-activated protein kinases (MAPKs) including p-Erk1/2 and p JNK showed a similar trend to the numbers of TUNEL- and caspase-3-positive cells. These results indicate that 1,3-DCP increases oxidative stress, nuclear translocation of Nrf2, and expression of Nrf2-targeted genes, followed by increased functional and histopathological alterations in the liver. The increase in hepatocellular apoptosis induced by 1,3-DCP may be related to oxidative stress mediated MAPK activation. PMID- 26143168 TI - Evaluation of propidium monoazide-quantitative PCR to detect viable Mycobacterium fortuitum after chlorine, ozone, and ultraviolet disinfection. AB - We evaluated whether propidium monoazide (PMA) combined with real-time quantitative PCR (qPCR) is suitable for detecting viable Mycobacterium fortuitum after chlorine, ozone, and ultraviolet (UV) disinfection. PMA-qPCR was effective in determining the viability of M. fortuitum compared with qPCR based on the membrane integrity. However, with a mild chlorine concentration, PMA-qPCR as an alternative method was not applicable due to a large gap between loss of culturability and membrane integrity damage. In ozonation, PMA-qPCR was able to differentiate between viable and injured mycobacteria, and the results were similar to those obtained by the culture method. Interestingly, PMA-qPCR was successful in monitoring the viability after UV disinfection due to the long UV exposure needed to effectively inactivate M. fortuitum. The findings of the present study suggested that the characteristics of disinfectants and the M. fortuitum resistance to disinfectants play critical roles in determining the suitability of PMA-qPCR for evaluating the efficacy of disinfection methods. PMID- 26143169 TI - Determination of perfluorinated sulfonate and perfluorinated acids in tissues of free-living European beaver (castor fiber L.) by d-SPE/ micro-UHPLC-MS/MS. AB - Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the main representatives of an rising class of persistent organic pollutants (POPs), perfluorochemicals (PFCs). In this study, determination of selected PFCs concentration in liver, brain, tail, adipose and peritoneum tissues of free living European beaver (Castor fiber L.) was addressed. Tissue samples, collected from beavers living in Masurian Lakeland (NE Poland), were analyzed by dispersive Solid Phase Extraction (d-SPE) with micro-UHPLC-MS/MS system. In a group of ten selected pefrluorinated compounds only two perfluorinated acids (PFOA and PFNA) and one perfluorinated sulfonate (PFOS) were quantified. PFOA was detected in all analysed tissue samples in both female and male beavers in a range from 0.55 to 0.98ngg(-1) ww whereas PFOS was identified in all analyzed female beaver tissues and only in liver, subcutaneous adipose and peritoneum tissues of male beavers at the concentration level from 0.86 to 5.08ngg(-1) ww. PFNA was only identified in female beaver tissues (liver, subcutaneous adipose and peritoneum) in a range from 1.50 to 6.61ngg(-1) ww. This study demonstrated the bioaccumulation of PFCs in tissue samples collected from beavers living in area known as green lungs of Poland. The results provided in this study indicate for the increasing risk of PFCs occurrence in the environment and the level of PFCs in tissue of free-living European beavers may serve as bioindicator of environmental pollution by these compounds. PMID- 26143170 TI - The evolving capabilities of rhodopsin-based genetically encoded voltage indicators. AB - Protein engineering over the past four years has made rhodopsin-based genetically encoded voltage indicators a leading candidate to achieve the task of reporting action potentials from a population of genetically targeted neurons in vivo. Rational design and large-scale screening efforts have steadily improved the dynamic range and kinetics of the rhodopsin voltage-sensing domain, and coupling these rhodopsins to bright fluorescent proteins has supported bright fluorescence readout of the large and rapid rhodopsin voltage response. The rhodopsin fluorescent protein fusions have the highest achieved signal-to-noise ratios for detecting action potentials in neuronal cultures to date, and have successfully reported single spike events in vivo. Given the rapid pace of current development, the genetically encoded voltage indicator class is nearing the goal of robust spike imaging during live-animal behavioral experiments. PMID- 26143171 TI - Effects of a pilot multidisciplinary clinic for frequent attending elderly patients on deprescribing. AB - OBJECTIVE: Multimorbidity and associated polypharmacy are risk factors for hospital re-admission. The Targeting Hospitalization Risks in Vulnerable Elders (THRIVE) clinic is a novel multidisciplinary out-patient clinic to improve transitions of care and decrease re-admission risk for older medical patients with frequent hospital admissions. This pilot study examined the effect of the THRIVE model on medication count, tablet load and potentially inappropriate medicines (PIMs). METHODS: Participants with frequent medical admissions were referred within 2 weeks of discharge from hospital and assessed at baseline and then at 4 and 12 weeks by the THRIVE team. A thorough reconciliation of all medications was performed collaboratively by a clinical pharmacist and a physician. Optimising medications, including deprescribing, was in collaboration with the participants' general practitioner. The complete medication history of each patient was compared retrospectively by an independent assessor at baseline and after the 12-week clinic, comparing total number of regular medications, tablet load and PIMs (measured using the Screening Tool of Older Persons Prescriptions (STOPP) tool). RESULTS: All 17 participants attending the pilot THRIVE clinic were included in the study. At 12 weeks, there was a significant reduction in mean medication count (from 14.3 to 11.2 medications; P < 0.001) and mean tablet load (from 20.5 to 16.9 tablets; P < 0.01). There was an absolute reduction in the total number of PIMs from 38 to 14. Common medications deprescribed included opioids, tricyclic antidepressants, benzodiazepines and diuretics. CONCLUSIONS: Patients who attended the THRIVE clinic had a significant reduction in medication count and tablet load. The pilot study demonstrates the potential benefits of a multidisciplinary out-patient clinic to improve prescribing and reduce unwarranted medications in an elderly population. An adequately powered comparative study would allow assessment of clinical outcomes and costs. PMID- 26143172 TI - The association of aphasia and right-sided motor impairment in corticobasal syndrome. AB - Corticobasal syndrome is defined clinically on the basis of symptoms and findings related to dysfunction of the cerebral cortex and the basal ganglia. Usually, marked asymmetry of motor findings is observed. Although aphasia has now been recognized as a frequent feature of corticobasal syndrome, it remains unclear whether it is usually associated with right-sided motor symptoms, pointing to the involvement of the left hemisphere. Hence, we set out to examine the relationship between the presence of language symptoms and the side affected by extrapyramidal symptoms. We analyzed the electronic care records of patients seen in the years 2003-2013 in the Neurology Department of the University Hospital of Munich. The diagnosis of corticobasal syndrome was discussed in ninety-two individuals. Of those, 38 cases fulfilled diagnostic criteria for corticobasal syndrome. Aphasia correlated highly with a predominant right-sided movement disorder (p = 0.002). In contrast, it was less common in patients with left-sided motor presentation. Dysarthria did not show a preferential correlation (p = 0.25). Our analysis suggests a characteristic presentation of corticobasal syndrome in which motor dysfunction of the right side of the body is associated with aphasia. PMID- 26143173 TI - Eruptive Tumors of the Follicular Infundibulum: An Unexpected Diagnosis of Hypopigmented Macules. AB - BACKGROUND: Tumor of the follicular infundibulum (TFI) is considered as a rare benign neoplasm providing two distinctive clinical patterns: the solitary and the eruptive form. The clinical presentations resemble many other dermatologic conditions and require histopathological study to make a definite diagnosis. OBJECTIVE: To inform physicians of a clinical presentation of TFI. CASE REPORT: We report on a 50-year-old man who presented with multiple asymptomatic hypopigmented macules resistant to the treatments. The histopathological study was consistent with tumors of the follicular infundibulum. CONCLUSION: Hypopigmented macules are one of the more common clinical presentations in dermatological practices. It is important to include TFI in the differential diagnosis when a patient with hypopigmented lesions does not respond to the treatment based on the clinical diagnosis. PMID- 26143175 TI - Behavior of accidentally released radiocesium in soil-water environment: Looking at Fukushima from a Chernobyl perspective. AB - Quantitative characteristics of dissolved and particulate radiocesium wash-off from contaminated watersheds after the FDNPP accident are calculated based on published monitoring data. Comparative analysis is provided for radiocesium wash off parameters and distribution coefficients, Kd, between suspended matter and water in rivers and surface runoff on Fukushima and Chernobyl contaminated areas for the first years after the accidents. It was found that radiocesium distribution coefficient in Fukushima rivers is essentially higher (1-2 orders of magnitude) than corresponding values for rivers and surface runoff within the Chernobyl zone. This can be associated with two factors: first, the high fraction of clays in the predominant soils and sediments of the Fukushima area and accordingly a higher value of the radiocesium Interception Potential, RIP, in general, and secondly the presence of water insoluble glassy particles containing radiocesium in the accidental fallout at Fukushima. It was found also that normalized dissolved wash-off coefficients for Fukushima catchments are 1-2 orders of magnitude lower than corresponding values for the Chernobyl zone. Normalized particulate wash-off coefficients are comparable for Fukushima and Chernobyl. Results of the investigation of radiocesium's ((134)Cs and (137)Cs) vertical distribution in soils of the close-in area of the Fukushima Dai-ichi NPP - Okuma town and floodplain of the Niida river are presented. The radiocesium migration in undisturbed forest and grassland soils at Fukushima contaminated area has been shown to be faster as compared to the Chernobyl 30-km zone during the first three years after the accidents. This may be associated with higher annual precipitation (by about 2.5 times) in Fukushima as compared to the Chernobyl zone, as well as the differences in the soil characteristics and temperature regime throughout a year. Investigation and analysis of Fukushima's radiocesium distribution in soils of Niida river catchment revealed accumulation zones of contaminated sediments on its floodplain. Average sediment deposition rates varied from 0.3 to 3.3 cm/year. PMID- 26143174 TI - Development of a concept for a personalized approach in the perioperative antiplatelet therapy administration/discontinuation management based on multiple electrode aggregometry in patients undergoing coronary artery surgery. AB - In patients undergoing coronary artery surgery, improvements in clinical outcomes currently rely on continued refinements of the surgical technique and modulation of adjuvant pharmacotherapy. Despite medical and technological advances, negligible rate of bleeding and ischemic events still persist necessitating further improvements in patient management. Platelet function testing (PFT) might play an important role in meticulous balancing between the risk of bleeding and thrombotic events. A suitable balance can be achieved by implementing a personalized, PFT based approach in antiplatelet therapy (APT) administration/discontinuation management. Despite emerging evidence on the widespread variability in platelet inhibitory response to APT, numerous PFT devices and heterogeneity in reporting study results hamper pooling of the evidence which in turn results with a lack of consensus in "on treatment" platelet reactivity associated with ischemic and bleeding events in perioperative phase. The literature on multiple electrode aggregometry (Multiplate((r)); Roche Diagnostics, Mannheim, Germany) in coronary artery disease patients was reviewed systematically. Based on the evidence evaluating the relationship between "drug specific" PFT and bleeding or adverse ischemic events, we sought to define therapeutic window for the most commonly administered antiplatelet drugs such as aspirin (ASPI test) and adenosine-diphosphate receptor blockers (ADP test). Preoperatively, APT administration was primarily focused to avoid bleeding complications. ASPI test value of 20 AUC and ADP test value of <73 AUC were set as cut-off values that delineate bleeding tendency. Postoperatively, "therapeutic window" was set to avoid both bleeding and adverse ischemic events. Therapeutic ranges were as follows: 20 AUC < ASPItest <= 30 AUC and 19AUC < ADP <= 46AUC, respectively. This is the first attempt to define PFT based "therapeutic window" according to, perioperative APT administration/discontinuation management would be targeted. It seems that the "one-size-fits-all" concept of perioperative APT administration management is outdated and further development of PFT based, personalized APT administration/discontinuation management is desirable. This concept therefore presents a possible step forward in patient care and provides a platform for further interventional trials whereby the impact of its application on clinical outcomes would be validated. PMID- 26143176 TI - A novel effect of DMOG on cell metabolism: direct inhibition of mitochondrial function precedes HIF target gene expression. AB - Abnormal accumulation of oncometabolite fumarate and succinate is associated with inhibition of mitochondrial function and carcinogenesis. By competing with alpha ketoglutarate, oncometabolites also activate hypoxia inducible factors (HIFs), which makes oncometabolite mimetics broadly utilised in hypoxia research. We found that dimethyloxalylglycine (DMOG), a synthetic analogue of alpha ketoglutarate, commonly used to induce HIF signalling, inhibits O2 consumption in cancer cell lines HCT116 and PC12, well before activation of HIF pathways. A rapid suppression of cellular respiration was accompanied by a decrease in histone H4 lysine 16 acetylation and not abolished by double knockdown of HIF 1alpha and HIF-2alpha. In agreement with this, production of NADH and state 3 respiration in isolated mitochondria were down-regulated by the de-esterified DMOG derivative, N-oxalylglycine. Exploring the roles of DMOG as a putative inhibitor of glutamine/alpha-ketoglutarate metabolic axis, we found that the observed suppression of OxPhos and compensatory activation of glycolytic ATP flux make cancer cells vulnerable to combined treatment with DMOG and inhibitors of glycolysis. On the other hand, DMOG treatment impairs deep cell deoxygenation in 3D tissue culture models, demonstrating a potential to relieve functional stress imposed by deep hypoxia on tumour, ischemic or inflamed tissues. Indeed, using a murine model of colitis, we found that O2 availability in the inflamed colon tissue rapidly increased after application of DMOG, which could contribute to the known therapeutic effect of this compound. Overall, our results provide new insights into the relationship between mitochondrial function, O2 availability, metabolic reprogramming and associated diseases. PMID- 26143177 TI - Lambert-Eaton myasthenic syndrome and prostatic adenocarcinoma. PMID- 26143178 TI - How reliable is internet-based self-reported identity, socio-demographic and obesity measures in European adults? AB - In e-health intervention studies, there are concerns about the reliability of internet-based, self-reported (SR) data and about the potential for identity fraud. This study introduced and tested a novel procedure for assessing the validity of internet-based, SR identity and validated anthropometric and demographic data via measurements performed face-to-face in a validation study (VS). Participants (n = 140) from seven European countries, participating in the Food4Me intervention study which aimed to test the efficacy of personalised nutrition approaches delivered via the internet, were invited to take part in the VS. Participants visited a research centre in each country within 2 weeks of providing SR data via the internet. Participants received detailed instructions on how to perform each measurement. Individual's identity was checked visually and by repeated collection and analysis of buccal cell DNA for 33 genetic variants. Validation of identity using genomic information showed perfect concordance between SR and VS. Similar results were found for demographic data (age and sex verification). We observed strong intra-class correlation coefficients between SR and VS for anthropometric data (height 0.990, weight 0.994 and BMI 0.983). However, internet-based SR weight was under-reported (Delta -0.70 kg [-3.6 to 2.1], p < 0.0001) and, therefore, BMI was lower for SR data (Delta -0.29 kg m(-2) [-1.5 to 1.0], p < 0.0001). BMI classification was correct in 93 % of cases. We demonstrate the utility of genotype information for detection of possible identity fraud in e-health studies and confirm the reliability of internet-based, SR anthropometric and demographic data collected in the Food4Me study. TRIAL REGISTRATION: NCT01530139 ( http://clinicaltrials.gov/show/NCT01530139 ). PMID- 26143179 TI - Identification of Mest/Peg1 gene expression as a predictive biomarker of adipose tissue expansion sensitive to dietary anti-obesity interventions. AB - Food components with anti-obesity properties are commonly evaluated using mouse models of diet-induced obesity. The ability of these components to reduce or prevent white adipose tissue (WAT) accumulation is usually tested in feeding trials of several weeks duration in order to detect significant effects on fat mass expansion. Here, we aimed to identify early, predictive biomarkers for WAT expansion. We performed a 5-day high-fat diet (HFD) feeding trial with C57BL/6J mice using different established anti-obesity interventions: epigallocatechin gallate, replacing dietary lipids by n-3 PUFA, and increasing dietary protein. WAT gene expression was analyzed of genes known to be similarly affected by short and long-term HFD. Gene expression of Leptin and Mest (mesoderm-specific transcript) was increased by HFD and normalized by all anti-obesity interventions. In a second experiment, translatability to whole blood-based expression data was assessed. Mice were challenged for 21 days with a HFD without or with simultaneous treatment with anti-obesity bioactives, hydroxytyrosol or resveratrol, and compared for parameters including Leptin and Mest expression in whole blood at day 5. While Leptin mRNA could not be detected in mouse whole blood, there was an induction of Mest mRNA by HFD which was suppressed by hydroxytyrosol. Moreover, Mest expression in whole blood at day 5 positively correlated with adiposity and negatively with lean body mass and the subcutaneous/visceral fat ratio at day 21. We conclude that gene expression of Leptin and Mest in WAT and of Mest in whole blood represent early, predictive markers of adipose tissue expansion of potential usefulness in nutritional studies and trials. PMID- 26143181 TI - The diversity of Bet v 1-specific IgG4 antibodies remains mostly constant during the course of birch pollen immunotherapy. PMID- 26143180 TI - Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial disease of unknown cause characterized by sinonasal inflammation, increased mucus production, and defective mucociliary clearance. Expression of Pendrin, an epithelial anion transporter, is increased in asthma and chronic obstructive pulmonary disease. Pendrin increases mucus production and regulates mucociliary clearance. OBJECTIVES: We sought to investigate the expression of pendrin and the mucus related protein Muc5AC in sinonasal tissues of control subjects and patients with CRS and to evaluate the regulation of pendrin expression in nasal epithelial cells (NECs) in vitro. METHODS: The expression and distribution of pendrin in sinonasal tissues was analyzed by using real-time PCR, immunoblot analysis, and immunohistochemistry. Differentiated NECs were used to study the regulation of pendrin expression. RESULTS: Increased pendrin expression was observed in nasal polyp (NP) tissue of patients with CRS. Immunohistochemistry analysis revealed that pendrin was largely restricted to the epithelial layer. Pendrin expression significantly correlated with inflammatory cell markers, suggesting that the factors made by these cells might induce pendrin expression. Furthermore, both pendrin and periostin levels (a biomarker in asthma) correlated with IL-13 levels, suggesting that pendrin can be induced by this cytokine in sinonasal tissues. Expression of the mucus component protein Muc5AC correlated weakly with pendrin expression, indicating that pendrin might modulate mucus production in NPs. In cultured NECs pendrin expression was induced by TH2 cytokines and induced synergistically when TH2 cytokines were combined with IL-17A. Interestingly, human rhinovirus had a potentiating effect on IL-13-induced pendrin expression. Dexamethasone suppressed pendrin expression, suggesting that the therapeutic benefit of dexamethasone in asthmatic patients and those with CRS might involve regulation of pendrin expression. CONCLUSIONS: TH2-mediated pendrin expression is increased in NPs of patients with CRS and might lead to increased inflammation, mucus production, and decreased mucociliary clearance. PMID- 26143182 TI - Association between insulin-like growth factor-1 and cardiovascular disease risk: Evidence from a meta-analysis. PMID- 26143183 TI - Immunotherapy for acute leukemia. PMID- 26143184 TI - Impact of insufficient drug efficacy of antiparkinson agents on patient's quality of life: a cross-sectional study. AB - BACKGROUND: To understand the current state of insufficient drug efficacy experienced by patients with Parkinson's disease (PD) and its effects on quality of life (QOL), we conducted a survey of patients with PD and analyzed the results from 2,630 completed questionnaires. METHODS: The questionnaires inquired about age, sex, Hoehn and Yahr stage, disease duration, drugs currently being taken, and the current state of insufficient drug efficacy; it also included items of the Parkinson's Disease Questionnaire-8 (PDQ-8). Questionnaires were mailed to members of the Japan Parkinson's Disease Association. RESULTS: Approximately 70% of all subjects reported some type of insufficient drug efficacy, and around half of these experienced this early in the morning or at night. The proportion of subjects who experienced insufficient drug efficacy was found to increase with greater disease severity according to the Hoehn and Yahr stage. However, even among patients with stage I severity, insufficient drug efficacy was reported by approximately 40% of the respondents. QOL was significantly lower in patients who experienced insufficient drug efficacy than in those who did not (PDQ-8 summary index; 42.0 +/- 20.1 vs. 30.0 +/- 19.5; p < 0.0001). CONCLUSIONS: These results suggest that insufficient drug efficacy might affect the quality of life of patients in most stages PD including the early stages. Therefore, greater awareness of insufficient drug efficacy gained by questioning patients might help medical practitioners in taking appropriate actions. PMID- 26143185 TI - What do Indian children drink when they do not receive water? Statistical analysis of water and alternative beverage consumption from the 2005-2006 Indian National Family Health Survey. AB - BACKGROUND: Over 1.2 billion people lack access to clean water. However, little is known about what children drink when there is no clean water. We investigated the prevalence of receiving no water and what Indian children drink instead. METHODS: We analysed children's beverage consumption using representative data from India's National Family and Health Survey (NFHS-3, 2005-2006). Consumption was based on mothers' reports (n = 22,668) for children aged 6-59 months (n = 30,656). RESULTS: About 10 % of Indian children had no water in the last 24 h, corresponding to 12,700,000 children nationally, (95 % CI: 12,260,000 to 13,200,000). Among children who received no water, 23 % received breast or fresh milk and 24 % consumed formula, "other liquid", juice, or two or more beverages. Children over 2 were more likely to consume non-milk beverages, including tea, coffee, and juice than those under 2 years. Those in the lowest two wealth quintiles were 16 % less likely to have received water (OR = 0.84; 95 % CI: 0.74 to 0.96). Compared to those living in households with bottled, piped, or tanker water, children were significantly less likely to receive water in households using well water (OR = 0.75; 95 % CI: 0.64 to 0.89) or river, spring, or rain water (OR =0.70; 95 % CI: 0.53 to 0.92) in the last 24 h. CONCLUSIONS: About 13 million Indian children aged 6-59 months received no water in the last 24 h. Further research is needed to assess the risks potentially arising from insufficient water, caffeinated beverages, and high sugar drinks at early stages of life. PMID- 26143187 TI - Spatial learning in men undergoing alcohol detoxification. AB - Alcohol dependence is a major public health problem worldwide. Brain and behavioral disruptions including changes in cognitive abilities are common features of alcohol addiction. Thus, the present study was aimed to investigate spatial learning and memory in 29 alcoholic men undergoing alcohol detoxification by using a virtual Morris maze task. As age-matched controls we recruited 29 men among occasional drinkers without history of alcohol dependence and/or alcohol related diseases and with a negative blood alcohol level at the time of testing. We found that the responses to the virtual Morris maze are impaired in men undergoing alcohol detoxification. Notably they showed increased latencies in the first movement during the trials, increased latencies in retrieving the hidden platform and increased latencies in reaching the visible platform. These findings were associated with reduced swimming time in the target quadrant of the pool where the platform had been during the 4 hidden platform trials of the learning phase compared to controls. Such increasing latency responses may suggest motor control, attentional and motivational deficits due to alcohol detoxification. PMID- 26143186 TI - Characteristics of A20 gene polymorphisms and clinical significance in patients with rheumatoid arthritis. AB - BACKGROUND: There are a number of studies regarding to the susceptibility of A20 SNPs in rheumatoid arthritis (RA); however, a few of these studies have shown an association between polymorphisms in the A20 gene and RA risk in the Chinese population. The aim of this study was to investigate the characteristics of A20 gene polymorphisms, the association between polymorphisms and clinical significance in Chinese RA patients. METHODS: PCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) (50 cases), synovial fluid (11 cases) from RA patients and PBMCs from 30 healthy individuals. Quantitative Real-time PCR (qRT-PCR) was used to analyze the A20 mRNA expression in 38 RA patients and 40 healthy individuals. Pearson's Chi square test and two independent-samples Wilcoxon tests were used for statistical analysis. RESULTS: Eight single nucleotide polymorphisms (SNPs) (rs5029937, rs3799491, rs598493, rs2307859, rs146534657, rs2230926, rs661561, and rs582757) were identified in PBMCs of RA patients. One new mutation (14284 T > A) was identified in synovial fluid mononuclear cells from one RA case. rs146534657 was identified for the first time in two RA cases. Patients with rs146534657 (12411 A > G, Asn102Ser) AG genotype or rs2230926 (12486 T > G, Phe127Cys) TG genotype had poor outcome. Significantly lower A20 mRNA expression was found in PBMCs from RA patients compared with healthy individuals (p < 0.001). There was a higher A20 mRNA expression in RA patients with rs2230926 TG genotype and rs146534657 AG genotype (11.56 +/- 7.39) than patients with rs2230926 TT genotype and rs146534657 AA genotype (5.63 +/- 4.37) (p = 0.031). CONCLUSION: Significantly lower A20 expression was found in RA patients. The polymorphisms of A20 were characterized in RA patients. We detected rs146534657 for the first time and identified a new A20 mutation (14284 T > A). A20 rs2230926 TG genotype and rs146534657 AG genotype may be related to poor outcome in RA patients. PMID- 26143188 TI - Behavioural and physiological responses of wood mice (Apodemus sylvaticus) to experimental manipulations of predation and starvation risk. AB - Body weight and the levels of stored body fat have fitness consequences. Greater levels of fat may provide protection against catastrophic failures in the food supply, but they may also increase the risk of predation. Animals may therefore regulate their fatness according to their perceived risks of predation and starvation: the starvation-predation trade-off model. We tested the predictions of this model in wood mice (Apodemus sylvaticus) by experimentally manipulating predation risk and starvation risk. We predicted that under increased predation risk individuals would lose weight and under increased starvation risk they would gain it. We simulated increased predation risk by playing the calls made by predatory birds (owls: Tyto alba and Bubo bubo) to the mice. Control groups included exposure to calls of a non-predatory bird (blackbird: Turdus merula) or silence. Mice exposed to owl calls at night lost weight relative to the silence group, mediated via reduced food intake, but exposure to owl calls in the day had no significant effect. Exposure to blackbird calls at night also resulted in weight loss, but blackbird calls in the day had no effect. Mice seemed to have a generalised response to bird calls at night irrespective of their actual source. This could be because in the wild any bird calling at night will be a predation risk, and any bird calling in the day would not be, because at that time the mice would normally be resting, and hence not exposed to avian predators. Consequently, mice have not evolved to distinguish different types of call but only to respond to the time of day that they occur. Mice exposed to stochastic 24h starvation events altered their behaviour (reduced activity) during the refeeding days that followed the deprivation periods to regain the lost mass. However, they only marginally elevated their food intake and consequently had reduced body weight/fat storage compared to that of the control unstarved group. This response may have been constrained by physiological factors (alimentary tract absorption capacity) or behavioural factors (perceived risk of predation). Overall the responses of the mice appeared to provide limited support for the starvation-predation trade-off model, and suggest that wood mice are much more sensitive to predation risk than they are to starvation risk. PMID- 26143189 TI - Effects of eating rate on satiety: A role for episodic memory? AB - Eating slowly is associated with a lower body mass index. However, the underlying mechanism is poorly understood. Here, our objective was to determine whether eating a meal at a slow rate improves episodic memory for the meal and promotes satiety. Participants (N=40) consumed a 400ml portion of tomato soup at either a fast (1.97ml/s) or a slow (0.50ml/s) rate. Appetite ratings were elicited at baseline and at the end of the meal (satiation). Satiety was assessed using; i) an ad libitum biscuit 'taste test' (3h after the meal) and ii) appetite ratings (collected 2h after the meal and after the ad libitum snack). Finally, to evaluate episodic memory for the meal, participants self-served the volume of soup that they believed they had consumed earlier (portion size memory) and completed a rating of memory 'vividness'. Participants who consumed the soup slowly reported a greater increase in fullness, both at the end of the meal and during the inter-meal interval. However, we found little effect of eating rate on subsequent ad libitum snack intake. Importantly, after 3h, participants who ate the soup slowly remembered eating a larger portion. These findings show that eating slowly promotes self-reported satiation and satiety. For the first time, they also suggest that eating rate influences portion size memory. However, eating slowly did not affect ratings of memory vividness and we found little evidence for a relationship between episodic memory and satiety. Therefore, we are unable to conclude that episodic memory mediates effects of eating rate on satiety. PMID- 26143190 TI - Treating Ebola patients: a 'bottom up' approach using generic statins and angiotensin receptor blockers. AB - The international community has responded to the Ebola outbreak in West Africa with a 'top down' approach. This has contributed to outbreak control, but has done much less to reduce the high mortality rate in individual patients. Ebola patients experience a breakdown in endothelial barrier integrity that leads to massive fluid losses and vascular collapse. Statins and angiotensin receptor blockers (ARBs) maintain or restore endothelial barrier integrity. Local physicians in Sierra Leone have treated approximately 100 consecutive Ebola patients with atorvastatin and irbesartan, and all but two inadequately treated patients have survived. The results of this experience have not been released and they need to be reviewed and validated. Unlike other treatments that target the Ebola virus itself, this 'bottom up' approach to treatment represents a paradigm shift by targeting the host response to infection. Treatment with these safe, inexpensive generic agents could be implemented readily throughout West Africa. PMID- 26143191 TI - Long-term risk of pancreatitis and diabetes after cholecystectomy in patients with cholelithiasis but no pancreatitis history: a 13-year follow-up study. AB - BACKGROUND & AIM: Patients with biliary pancreatitis are suggested to undergo cholecystectomy to prevent the recurrence of pancreatitis. However, it remains controversial whether cholecystectomy is associated with reduced risks of pancreatitis and diabetes in patients with cholelithiasis and no history of pancreatitis. METHODS: From Taiwan's National Health Insurance Research Database, we identified the following cohorts and analyzed the long-term risks of pancreatitis and diabetes in each cohort: 1) cholecystectomy cohort: cholelithiasis patients who had no history of pancreatitis and diabetes and underwent cholecystectomy; and 2) comparison cohort: cholelithiasis patients who had no history of pancreatitis and diabetes and did not undergo cholecystectomy. RESULTS: The cholecystectomy group and the comparison group had similar distributions of age, sex, and comorbidities, except for hyperlipidemia. The proportion of patients in the cholecystectomy group who underwent endoscopic cholangiographic procedures was higher than that in the comparison group. Cholecystectomy was associated with a reduced risk of pancreatitis (adjusted hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.36-0.68). Age-specific analyses showed that pancreatitis risk was decreased in patients younger than 50 and older than 65years. Both men and women exhibited reduced risks of pancreatitis after cholecystectomy. However, cholecystectomy was not associated with changes in the risk for diabetes. CONCLUSION: Cholecystectomy for cholelithiasis is associated with a reduced risk of pancreatitis, but not of diabetes, in patients without previous history of pancreatitis and diabetes. PMID- 26143193 TI - Evaluation and selection of emergency treatment technology based on dynamic fuzzy GRA method for chemical contingency spills. AB - A robust scheme to address emergency pollution accident is becoming more and more important with the rise of the frequency and intensity of the emergency pollution accidents. Therefore, it is crucial to select an appropriate technology in an emergency response to chemical spills. In this study, an evaluation framework based on dynamic fuzzy GRA method has been developed to make forward optimum scheme for the selection of emergency treatment technology. Dynamic analysis and linguistic terms are used to evaluate alternatives to improve efficiency of emergency treatment procedures by addressing the vagueness and ambiguity in decision making. The method was then applied in a case study to evaluate emergency arsenic treatment technology and demonstrate its applicability and feasibility in emergency arsenic pollution under two scenarios associated with different arsenic levels. Therefore, not only the results can be used for selecting emergency treatment technology, but also help decision-makers identify desired decisions for contaminant mitigation with a quick response and cost effective manner. PMID- 26143194 TI - Fluoride adsorption by doped and un-doped magnetic ferrites CuCe(x)Fe(2-x)O4: Preparation, characterization, optimization and modeling for effectual remediation technologies. AB - A series of doped and un-doped magnetic adsorbents CuCexFe2-xO4 (x=0.0-0.5) for fluoride were prepared with the micro-emulsion method. Fluoride adsorption was optimized for solution pH, temperature, contact time, and initial concentration and was monitored via normal phase ion chromatography (IC). The effect of concomitant anions was also explored to perform and simulate competitive fluoride adsorption in real water samples. Optimal adsorption was discovered by a simple quadratic model based on central composite design (CCD) and the response surface method (RSM). The adsorption, electrochemical and magnetic properties were compared between doped and un-doped ferrites. Doped ferrites (x=0.1-0.5) were found to be superior to un-doped ferrites (x=0) regarding the active sites, functional groups and fluoride adsorption. The characterization, optimization and application results of the doped ferrites indicated enhanced fluoride adsorption and easy separation with a simple magnet. PMID- 26143192 TI - Deletion of WASp and N-WASp in B cells cripples the germinal center response and results in production of IgM autoantibodies. AB - Humoral immunodeficiency caused by mutations in the Wiskott-Aldrich syndrome protein (WASp) is associated with failure to respond to common pathogens and high frequency of autoimmunity. Here we addressed the question how deficiency in WASp and the homologous protein N-WASp skews the immune response towards autoreactivity. Mice devoid of WASp or both WASp and N-WASp in B cells formed germinal center to increased load of apoptotic cells as a source of autoantigens. However, the germinal centers showed abolished polarity and B cells retained longer and proliferated less in the germinal centers. While WASp-deficient mice had high titers of autoreactive IgG, B cells devoid of both WASp and N-WASp produced mainly IgM autoantibodies with broad reactivity to autoantigens. Moreover, B cells lacking both WASp and N-WASp induced somatic hypermutation at reduced frequency. Despite this, IgG1-expressing B cells devoid of WASp and N WASp acquired a specific high affinity mutation, implying an increased BCR signaling threshold for selection in germinal centers. Our data provides evidence for that N-WASp expression alone drives WASp-deficient B cells towards autoimmunity. PMID- 26143195 TI - Facile and economical synthesis of porous activated semi-cokes for highly efficient and fast removal of microcystin-LR. AB - To mitigate the threat of microcystins on the environment and human health, we demonstrate for the first time that porous activated semi-cokes (ASCs) with average pore diameters of 2-20 nm could be used as adsorbents for the fast and efficient removal of microcystin-LR (MC-LR). The surface physicochemical properties of ASCs were carefully investigated and their relations with the adsorption performance were discussed. The results showed that ASCs activated by HNO3 and KOH exhibited excellent adsorption capacities of 4276 and 8430 MUg/g, respectively, which were nearly 5 times and 10 times higher than that of activated carbon (AC). ASCs also showed a fast adsorption property by over 95% recovery of MC-LR in the initial 10 min. The overall adsorption of MC-LR on ASCs might be dominated by both external diffusion and intra-particle diffusion. In addition, ASCs manifested an outstanding reusability and the adsorption of MC-LR was hardly influenced by the coexisting fulvic acid at low concentration. Given the remarkable performance and low cost, activated semi-cokes are expected to present promising potentials for the practical application in removing microcystins from aqueous solutions. PMID- 26143196 TI - Fabrication and characterization of hollow CdMoO4 coupled g-C3N4 heterojunction with enhanced photocatalytic activity. AB - This research was designed for the first time to investigate the activities of CdMoO4/g-C3N4 heterojunction in photocatalytic degradation of rhodamine B (RhB) and converting CO2 to fuels. The composite was synthesized via a simple mixing calcination method and characterized by various techniques including Brunauer Emmett-Teller method (BET), X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X ray photoelectron spectroscopy, UV-vis diffuse reflectance spectroscopy, photoluminescence spectroscopy, and electrochemical method. The results showed that the introduction of CdMoO4 to g-C3N4 exerted little effect on the property of light absorption, but resulted in an increase in the BET surface area, which was beneficial for the adsorption of RhB. More importantly, formation of a hetero junction structure between CdMoO4 and g-C3N4 significantly promoted the separation of electron-hole pairs and ultimately enhanced the photocatalytic activity. The optimal CdMoO4/g-C3N4 composite could degrade RhB 6.5 times faster than pure g-C3N4 under visible light irradiation. Meanwhile, the composite showed a CO2 conversion rate of 25.8 MUmol h(-1) gcat(-1), which was 4.8 and 8.1 times higher than those of g-C3N4 and P25, respectively, under simulated sunlight irradiation. This work might represent an important step in simultaneous environmental protection and energy production by g-C3N4 based materials. PMID- 26143197 TI - Comparison of three combined sequencing batch reactor followed by enhanced Fenton process for an azo dye degradation: Bio-decolorization kinetics study. AB - The purpose of this research was to compare three combined sequencing batch reactor (SBR) - Fenton processes as post-treatment for the treatment of azo dye Acid Red 18 (AR18). Three combined treatment systems (CTS1, CTS2 and CTS3) were operated to investigate the biomass concentration, COD removal, AR18 dye decolorization and kinetics study. The MLSS concentration of CTS2 reached 7200 mg/L due to the use of external feeding in the SBR reactor of CTS2. The COD concentration remained 273 mg/L and 95 mg/L (initial COD=3270 mg/L) at the end of alternating anaerobic-aerobic SBR with external feeding (An-A MSBR) and CTS2, respectively, resulting in almost 65% of Fenton process efficiency. The dye concentration of 500 mg/L was finally reduced to less than 10mg/L in all systems indicating almost complete AR18 decolorization, which was also confirmed by UV vis analysis. The dye was removed following two successive parts as parts 1 and 2 with pseudo zero-order and pseudo first-order kinetics, respectively, in all CTSs. Higher intermediate metabolites degradation was obtained using HPLC analysis in CTS2. Accordingly, a combined treatment system can be proposed as an appropriate and environmentally-friendly system for the treatment of the azo dye AR18 in wastewater. PMID- 26143198 TI - Gamma radiation/H2O2 treatment of a nonylphenol ethoxylates: Degradation, cytotoxicity, and mutagenicity evaluation. AB - Gamma radiation/H2O2 treatment of nonylphenol polyethoxylates (NPEO) was performed and treatment effect was evaluated on the basis of degradation, chemical oxygen demand (COD) and total organic carbon (TOC), and toxicity reduction efficiencies. The radiolytic by-products were determined by Fourier Transform Infrared Spectroscopy (FTIR), High-Performance Liquid Chromatography (HPLC), and Gas Chromatography-Mass Spectrometry (GC-MS) techniques. Low mass carboxylic acids, aldehyde, ketone, and acetic acid were identified as the by products of the NPEO degradation. NPEO sample irradiated to the absorbed dose of 15 kGy/4.58% H2O2 showed more than 90% degradation. Allium cepa (A. cepa), brine shrimp, heamolytic tests were used for cytotoxicity study, while mutagenicity was evaluated through Ames test (TA98 and TA100 strains) of treated and un-treated NPEO. The reductions in COD and TOC were greater than 70% and 50%, respectively. Gamma radiation/H2O2 treatment revealed a considerable reduction in cytotoxicity and mutagenicity. A. cepa, heamolytic and shrimp assays showed cytotoxicity reduction up to 68.65%, 77%, and 94%, respectively. The mutagenicity reduced up to 62%, 74%, and 79% (TA98) and 68%, 78%, and 82% (TA100), respectively of NPEO 6, NPEO-9, and NPEO-30 irradiated to the absorbed dose of 15 kGy/4.58% H2O2. NPEO 6 detoxified more efficiently versus NPEO-9 and NPEO-30 and results showed that Gamma radiation/H2O2 treatment has the potential to mineralize and detoxify NPEO. PMID- 26143199 TI - Proteomic analysis of cell proliferation in a human hepatic cell line (HL-7702) induced by perfluorooctane sulfonate using iTRAQ. AB - Perfluorooctane sulfonate (PFOS) is a commonly used and widely distributed perfluorinated compound proven to cause adverse health outcomes. However, how PFOS affects liver cell proliferation is not well understood. In this experiment, we exposed a human liver cell line (HL-7702) to 50 MUM PFOS for 48 h and 96 h. We identified 52 differentially expressed proteins using a quantitative proteomic approach. Among them, 27 were associated with cell proliferation, including hepatoma-derived growth factor (Hdgf) and proliferation biomarkers Mk167 (Ki67) and Top2alpha. Results from MTT, cell counting, and cell cycle analysis showed low-dose PFOS (<200 MUM) stimulated HL-7702 cell viability at 48 h and 96 h, reduced the G0/G1 percentage, and increased the S+G2/M percentage. Moreover, levels of Cyclin D1, Cyclin E2, Cyclin A2, Cyclin B1 and their partner Cdks were elevated, and the expression of regulating proteins like c-Myc, p53, p21 waf/cip1 and Myt1, as well as the phosphorylation levels of p-Wee1(S642), p-Chk1(S345) and p-Chk2(T68), were disturbed. We hypothesized that low-dose PFOS stimulated HL 7702 proliferation by driving cells into G1 through elevating cyclins/cdks expression, and by promoting cell cycle progression through altering other regulating proteins. This research will shed light on the mechanisms behind PFOS mediated human hepatotoxicity. PMID- 26143200 TI - Phytoremediation capacity of aquatic plants is associated with the degree of phytochelatin polymerization. AB - Phytochelatins (PCs) play important role in phytoremediation as heavy metal binding peptides. In the present study, the association between heavy metal removal capacity and phytochelatin synthesis was compared through the examination of three aquatic plants: Elodea canadensis, Salvinia natans and Lemna minor. In case of a Cd treatment, or a Cd treatment combined with Cu and Zn, the highest removal capacity was observed in L. minor. At the same time, E. canadensis showed the lowest removal capacity except for Zn. The heavy metal-induced (Cu+Zn+Cd) oxidative stress generated the highest ascorbate level in L. minor. Cd in itself or combined with the other two metals induced a 10-15-fold increase in the amount of gamma-glutamylcysteine in L. minor while no or smaller changes were observed in the other two species. Correspondingly, the total PC content was 6-8-fold greater in L. minor. In addition, PCs with higher degree of polymerization were only observed in L. minor (PC4, PC6 and PC7) while PC2 and PC3 occurred in E. canadensis and S. natans only. The correlation analysis indicated that the higher phytoremediation capacity of L. minor was associated with the synthesis of PCs and their higher degree of polymerization. PMID- 26143201 TI - The neural mechanism underlying recollection is sensitive to the quality of episodic memory: Event related potentials reveal a some-or-none threshold. AB - Although much is known about the underlying neural systems that support recollection, exactly how recollection operates remains unclear. One possibility is that recollection reflects the operation of a continuous retrieval process, whereby test cues always elicit some information from memory. Alternatively, recollection may reflect the operation of a thresholded process that allows for retrieval failure, whereby test cues sometimes elicit no information from memory at all. Here we demonstrate that recollection is thresholded by measuring a commonly reported electrophysiological correlate of episodic retrieval--known as the Left Parietal old/new effect. We use a novel source task designed to directly measure the accuracy of retrieval success, finding that the neural correlate of retrieval was sensitive to the precision of responses when recollection succeeded, but was absent when recollection failed. The results clarify the nature of the neural mechanism underlying episodic memory, providing novel evidence in support of some-or-none threshold models of recollection. PMID- 26143202 TI - XNAT Central: Open sourcing imaging research data. AB - XNAT Central is a publicly accessible medical imaging data repository based on the XNAT open-source imaging informatics platform. It hosts a wide variety of research imaging data sets. The primary motivation for creating XNAT Central was to provide a central repository to host and provide access to a wide variety of neuroimaging data. In this capacity, XNAT Central hosts a number of data sets from research labs and investigative efforts from around the world, including the OASIS Brains imaging studies, the NUSDAST study of schizophrenia, and more. Over time, XNAT Central has expanded to include imaging data from many different fields of research, including oncology, orthopedics, cardiology, and animal studies, but continues to emphasize neuroimaging data. Through the use of XNAT's DICOM metadata extraction capabilities, XNAT Central provides a searchable repository of imaging data that can be referenced by groups, labs, or individuals working in many different areas of research. The future development of XNAT Central will be geared towards greater ease of use as a reference library of heterogeneous neuroimaging data and associated synthetic data. It will also become a tool for making data available supporting published research and academic articles. PMID- 26143203 TI - Functional MRI during hyperbaric oxygen: Effects of oxygen on neurovascular coupling and BOLD fMRI signals. AB - Hyperbaric oxygen (HBO) therapy is used to treat a number of ailments. Improved understanding of how HBO affects neuronal activity, cerebral blood flow (CBF) and blood-oxygenation-level dependent (BOLD) changes could shed light on the role of oxygen in neurovascular coupling and help guide HBO treatments. The goal of this study was to test two hypotheses: i) activation-induced CBF fMRI response is not dependent on hemoglobin deoxygenation, and ii) activation-induced BOLD fMRI is markedly attenuated under HBO. CBF and BOLD fMRI of forepaw stimulation in anesthetized rats under HBO at 3 atmospheres absolute (ATA) were compared with normobaric air. Robust BOLD and CBF fMRI were detected under HBO. Inflow effects and spin-density changes did not contribute significantly to the BOLD fMRI signal under HBO. Analysis of the T2(*)-weighted signal at normobaric air and 1, 2 and 3ATA oxygen in the tissue and the superior sagittal sinus showed a strong dependence on increasing inhaled [O2]. Spontaneous electrophysiological activity and evoked local-field potentials were reduced under HBO. The differences between normobaric air and HBO in basal and evoked electrical activity could not fully account for the strong BOLD responses under HBO. We concluded that activation induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism and that stimulus-evoked BOLD responses and the venous T2(*)-weighted signals still have room to increase under 3ATA HBO. To our knowledge, this is the first fMRI study under HBO, providing insights into the effects of HBO on neural activity, neurovascular coupling, tissue oxygenation, and the BOLD signal. PMID- 26143204 TI - Nigrostriatal dopamine-independent resting-state functional networks in Parkinson's disease. AB - As an indicator of synchronous neural activity, resting-state functional networks are influenced by neuropathological and neurochemical changes in degenerative diseases. To further advance understanding about neurochemical and neuropathological basis for resting-state functional maps, we performed a comparative analysis of resting-state functional connectivity in patients with Parkinson's disease (PD) and drug induced parkinsonism (DIP). Resting-state neuroimaging data were analyzed with a seed-based approach to investigate striatocortical functional connectivity and cortical functional connectivity within the default mode network, executive control network, and the dorsal attention network. The striatal subregions were divided into the more or less affected sides in terms of dopamine transporter uptake. Compared with DIP, PD exhibited an increased cerebellar connectivity from the more affected side of the caudate and the less affected sides of the anterior and the posterior putamen. Additionally, PD showed increased functional connectivity in the anterior prefrontal areas from the more affected side of the anterior putamen and from the less affected side of the posterior putamen. However, PD exhibited decreased cortical functional connectivity from the posterior cingulate cortex in the left temporal area. Finally, DIP patients showed decreased cortical functional connectivity from the dorsolateral prefrontal cortex in frontal and parietal areas compared with PD patients. In summary, the present study demonstrates that PD patients exhibited a unique resting state functional connectivity that may be associated with PD-related pathological changes beyond the dopaminergic system, whereas DIP patients showed altered functional connectivity within executive control network. PMID- 26143205 TI - Microstructure of the superior longitudinal fasciculus predicts stimulation induced interference with on-line motor control. AB - A cortical visuomotor network, comprising the medial intraparietal sulcus (mIPS) and the dorsal premotor area (PMd), encodes the sensorimotor transformations required for the on-line control of reaching movements. How information is transmitted between these two regions and which pathways are involved, are less clear. Here, we use a multimodal approach combining repetitive transcranial magnetic stimulation (rTMS) and diffusion tensor imaging (DTI) to investigate whether structural connectivity in the 'reaching' circuit is associated to variations in the ability to control and update a movement. We induced a transient disruption of the neural processes underlying on-line motor adjustments by applying 1Hz rTMS over the mIPS. After the stimulation protocol, participants globally showed a reduction of the number of corrective trajectories during a reaching task that included unexpected visual perturbations. A voxel-based analysis revealed that participants exhibiting higher fractional anisotropy (FA) in the second branch of the superior longitudinal fasciculus (SLF II) suffered less rTMS-induced behavioral impact. These results indicate that the microstructural features of the white matter bundles within the parieto-frontal 'reaching' circuit play a prominent role when action reprogramming is interfered. Moreover, our study suggests that the structural alignment and cohesion of the white matter tracts might be used as a predictor to characterize the extent of motor impairments. PMID- 26143206 TI - Same clock, different time read-out: Spontaneous brain oscillations and their relationship to deficient coding of cognitive content. AB - Neuronal oscillations provide an efficient means of communication, fostering functional neural states supporting action and reaction. High in the action hierarchy, cognitive abilities are severely compromised in neuropsychiatric disease such as schizophrenia. Current thinking highlights a clocking mechanism provided by the phase of an ongoing slow oscillation that offers a temporal frame for coding of perceptual and computational elements. Yet unclear is whether and how a dysregulated clocking mechanism accounts for diminished cognitive performance. Neuromagnetic oscillatory activity was related to cognitive performance assessed by the MATRICS Consensus Cognitive Battery in 58 healthy individuals (HC) and 46 schizophrenia patients (SZ). HC showed a correlation between gamma-band oscillations (>40 Hz) and working memory performance. This relationship was disrupted in several ways in SZ. First, patients evidenced lower gamma power, poorer working memory performance, and no relationship between these measures. Second, the power spectra were dominated by ~10 Hz alpha oscillations with no group differences in amplitude. However, analysis of phase-to-amplitude coupling (PAC) revealed exaggerated clocking of gamma activity by alpha phase in SZ, associated with poor working memory performance. Third, despite entrainment by the same 10 Hz clock, gamma amplitude was abnormally distributed across the duty cycle in SZ, a potential consequence of compromised interneuron inhibition. Fourth, SZ showed over-engagement of a fronto-parietal network measured by gamma phase coherence, suggesting a brain state hindering cognitive output. Such an endogenous temporal organization may be a core dysfunction in SZ: a segregation/integration input imbalance fostering reduced cognitive performance and compromised behavioral output. PMID- 26143207 TI - Minimum variance beamformer weights revisited. AB - Adaptive minimum variance beamformers are widely used analysis tools in MEG and EEG. When the target brain activity presents in the form of spatially localized responses, the procedure usually involves two steps. First, positions and orientations of the sources of interest are determined. Second, the filter weights are calculated and source time courses reconstructed. This last step is the object of the current study. Despite different approaches utilized at the source localization stage, basic expressions for the weights have the same form, dictated by the minimum variance condition. These classic expressions involve covariance matrix of the measured field, which includes contributions from both the sources of interest and the noise background. We show analytically that the same weights can alternatively be obtained, if the full field covariance is replaced with that of the noise, provided the beamformer points to the true sources precisely. In practice, however, a certain mismatch is always inevitable. We show that such mismatch results in partial suppression of the true sources if the traditional weights are used. To avoid this effect, the "alternative" weights based on properly estimated noise covariance should be applied at the second, source time course reconstruction step. We demonstrate mathematically and using simulated and real data that in many situations the alternative weights provide significantly better time course reconstruction quality than the traditional ones. In particular, they a) improve source-level SNR and yield more accurately reconstructed waveforms; b) provide more accurate estimates of inter-source correlations; and c) reduce the adverse influence of the source correlations on the performance of single-source beamformers, which are used most often. Importantly, the alternative weights come at no additional computational cost, as the structure of the expressions remains the same. PMID- 26143208 TI - Temporal unpredictability of a stimulus sequence and the processing of neutral and emotional stimuli. AB - Most experimental settings in cognitive neuroscience present a temporally structured stimulus sequence, i.e., stimuli may occur at either constant and predictable or variable and less predictable inter-stimulus intervals (ISIs). This experimental feature has been shown to affect behavior and activation of various cerebral structures such as the parietal cortex and the amygdala. Studies employing explicit or implicit cues to manipulate predictability of events have shown that unpredictability particularly accentuates the response to events of negative valence. The present study investigates whether the effects of unpredictability are similarly affected by the emotional content of stimuli when unpredictability is induced simply by the temporal structure of a stimulus sequence, i.e., by variable as compared to constant ISIs. In an fMRI study, we applied three choice-reaction-time tasks with stimuli of different social emotional content. Subjects (N=30) were asked to identify the gender in angry and happy faces, or the shape of geometric figures. Tasks were performed with variable and constant ISIs. During the identification of shapes, variable ISIs increased activation in widespread areas comprising the amygdala and fronto parietal regions. Conversely, variable ISIs during gender identification resulted in a decrease of activation in a small region near the intraparietal sulcus. Our findings reveal that variability in the temporal stimulus structure of an experimental setting affects cerebral activation depending on task demands. They suggest that the processing of emotional stimuli of different valence is not much affected by the decision of employing a constant or a variable temporal stimulus structure, at least in the context of implicit emotion processing tasks. In contrast, temporal structure diversely affects the processing of neutral non social compared to emotional stimuli, emphasizing the relevance of considering this experimental feature in studies which aim at differentiating social emotional from cognitive processing in general, and more particularly, aim at identifying circumscribed alterations of social cognition in mental disorders. PMID- 26143209 TI - Successful memory formation is driven by contextual encoding in the core memory network. AB - To understand how memories are successfully formed, scientists have compared neural activity during the encoding of subsequently remembered and forgotten items. Though this approach has elucidated a network of brain regions involved in memory encoding, this method cannot distinguish broad, non-specific signals from memory specific encoding processes, such as associative encoding. Associative encoding, which is a key mechanism of learning, can be seen in the tendency of participants to successively recall, or cluster, study neighbors. We assessed the electrophysiological correlates of associative processing by comparing intracranially recorded EEG activity during the encoding of items that were subsequently recalled and clustered; recalled and not clustered; or not recalled. We found that high frequency activity (HFA) in left prefrontal cortex, left temporal cortex and hippocampus increased during the encoding of subsequently recalled items. Critically, the magnitude of this effect was largest for those recalled items that were also subsequently clustered. HFA temporally dissociated across regions, with increases in left prefrontal cortex preceding those in hippocampus. Furthermore, late hippocampal HFA positively correlated with behavioral measures of clustering. These results suggest that associative processes linking items to their spatiotemporal context underlie the traditionally observed subsequent memory effect and support successful memory formation. PMID- 26143210 TI - Solvent resistance pumps of Pseudomonas putida S12: Applications in 1-naphthol production and biocatalyst engineering. AB - The solvent resistance capacity of Pseudomonas putida S12 was applied by using the organism as a host for biocatalysis and through cloning and expressing solvent resistant pump genes into Escherichia coli. P. putida S12 expressing toluene ortho mononooxygenase (TOM-Green) was used for 1-naphthol production in a water-organic solvent biphasic system. Application of P. putida S12 improved 1 naphthol production per gram cell dry weight by approximately 42% compared to E. coli. Moreover, P. putida S12 enabled the use of a less expensive solvent, decanol, for 1-naphthol production. The solvent resistant pump (srpABC) genes of P. putida S12 were cloned into a solvent sensitive E. coli strain to transfer solvent tolerance. Recombinant strains bearing srpABC genes in either a low-copy number or a high-copy number plasmid grew in the presence of saturated concentration of toluene. Both of the recombinant strains were more tolerant to 1% v/v of toxic solvents, decanol and hexane, reaching similar cell density as the no-solvent control. Reverse-transcriptase analysis revealed that the srpABC genes were transcribed in engineered strains. The results demonstrate successful transfer of the proton-dependent solvent resistance mechanism and suggest that the engineered strain could serve as more robust biocatalysts in media with organic solvents. PMID- 26143211 TI - [What have the associations become?]. PMID- 26143212 TI - [Control the risks of treatment]. PMID- 26143213 TI - [The risk/benefit ratio in psychiatry]. AB - The risk/benefit ratio weighs up on the one hand the expected advantages and on the other the potential risks of a procedure. It is taken into consideration with every therapeutic decision, whether it concerns medication-based treatments, psychotherapy or any other type of treatment. The ethical dimension is a critical element which must be taken into account during team deliberations, whenever these are possible. PMID- 26143214 TI - [Psychiatry, the field of all risks]. AB - Mental disorders lead patients along paths of irrationality. Insanity is perceived as excessiveness, often associated with violence. Risk in psychiatry is omnipresent and nursing practice is performed within a narrow safety zone. The media coverage of sensitive situations does not help. Ensuring the patient's recovery, respecting the fundamental principles of individual freedom while assuring the utmost safety of others is the constant challenge facing caregivers in psychiatry. PMID- 26143215 TI - ["There can be no unnecessary risks"]. AB - The psychoanalytical point of view regarding the notion of risks helps us to understand the concept of transference and counter transference. Practice analysis groups provide an opportunity for collective discussion and the sharing of experience of clinical situations. Interview with Didier Gauchy, a psychiatrist-psychoanalyst in Lyon. PMID- 26143216 TI - [An emergency team working closely with the patient]. AB - ERIC 77 is a rapid response team for emergency psychiatric situations. This cross sector service based at Marne-la-Vallee general hospital represents a supplementary network in psychiatric patient care. The analysis of the professionals receiving calls as well as the link with the sector are critical in determining the success of patient care. Each risk is measured in order to provide adapted and personalised care. PMID- 26143217 TI - [Tony, at risk of getting lost]. AB - For some long-term hospital patients, certain care options involve risk-taking for the patient and for the teams. The assessment of these risks, even if they are to some extent unknown, must be discussed and weighed up. The teams must therefore anticipate situations and find alternatives which will ensure the success of the project. PMID- 26143218 TI - [Cooking as a therapy for dangerous mental health patients: controlled risk taking]. AB - Among the range of therapeutic mediators used with dangerous mental health patients in the unit for dangerous patients in Cadillac, cooking holds an important place. Led by caregivers, this activity has undeniable positive effects for the psychotic and non-psychotic patients taking part. These effects concern notably their capacities for conception, creation, organisation, execution, sensation, collaboration and socialisation. For some patients, it is also the opportunity to take the drama out of handling utensils which they previously used as weapons. As the risk factors are controlled before and during the activity, no dangerous acting out has ever occurred. PMID- 26143219 TI - [Compulsory admission to hospital in Tunisia: a necessary evolution]. AB - The evolution of the legislation governing compulsory admission to hospital in Tunisia is interesting for two reasons. The country's 2011 revolution notably brought about major changes to the legislative framework, from constitutional through to ordinary laws. At the same time, the current trend for globalisation is also affecting legislation: international laws, treaties and UN charters are imposed on the laws of individual countries. This article looks at how Tunisian law governing compulsory admission to hospital has had to evolve. PMID- 26143220 TI - [Motivational interview: supporting change]. AB - The motivational interview aims to help patients to resolve their ambivalence regarding problematic behaviors and to guide them into change. It differs from other therapeutic approaches mainly through the attitude of the therapist. In motivational interviewing, the therapist defends the statu quo. By reactance, the patient defends the change and enhance her/his motivation. This article provides a summary of the other concepts of motivational interviewing and its applications in the psychiatric daily practice. PMID- 26143221 TI - [3/5 Didier Anzieu]. PMID- 26143222 TI - Following the transfer of DNA: How does the presence of background DNA affect the transfer and detection of a target source of DNA? AB - DNA transfer is of increasing importance in crime scene situations, partly due to analytical techniques detecting profiles in ever declining amounts of DNA. Whereas the focus has previously been DNA transfer of target sources, the effects of background DNA on transfer and detection of DNA after multiple contact situations have been much less investigated. This study measured the transfer and detection rates of a specific DNA source in the presence of background DNA sources. The presence of background DNA influenced the transfer of DNA differently depending on the combination of biological material and surface type. The detection of a profile from the target DNA decreased after multiple contact situations, due to the reduced total and relative quantity of target DNA, and the increasing complexity of the mixture. The results of this study contribute to a greater understanding of the effects of background DNA sources on DNA transfer and detection. PMID- 26143223 TI - Impact of Postapproval Evidence Generation on the Biopharmaceutical Industry. AB - PURPOSE: Meeting marketplace demands for proving the value of new products requires more data than the industry has routinely produced. These data include evidence from comparative effectiveness research (CER), including randomized, controlled trials; pragmatic clinical trials; observational studies; and meta analyses. METHODS: We designed and conducted a survey to examine the industry's perceptions on new data requirements regarding CER evidence, the acceptability of postapproval study types, payer-specific issues related to CER, communication of data being generated postapproval, and methods used for facilitating postapproval evidence generation. FINDINGS: CER is being used by payers for most types of postapproval decisions. Randomized, controlled trials were indicated as the most acceptable form of evidence. At the same time, there was support for the utility of other types of studies, such as pragmatic clinical trials and observational studies. Respondents indicated the use of multiple formats for communicating postapproval data with many different stakeholders including regulators, payers, providers, and patients. Risk-sharing agreements with payers were unanimously supported by respondents with regard to certain products with unclear clinical and economic outcomes at launch. In these instances, conditional reimbursement through coverage with evidence development was considered a constructive option. The Food and Drug Administration's initiative called Regulatory Science was considered by the respondents as having the most impact on streamlining the generation of postapproval research-related evidence. IMPLICATIONS: The biopharmaceutical industry is faced with a broad and complex set of challenges related to evidence generation for postapproval decisions by a variety of health care system stakeholders. Uncertainty remains as to how the industry and payers use postapproval studies to guide decision making with regard to pricing and reimbursement status. Correspondingly, there is uncertainty regarding whether the industry's investment in CER will have a positive return on investment in terms of reimbursement and market access. PMID- 26143224 TI - Exosome mediated communication within the tumor microenvironment. AB - It is clear that exosomes (endosome derived vesicles) serve important roles in cellular communication both locally and distally and that the exosomal process is abnormal in cancer. Cancer cells are not malicious cells; they are cells that represent 'survival of the fittest' at its finest. All of the mutations, abnormalities, and phenomenal adaptations to a hostile microenvironment, such as hypoxia and nutrient depletion, represent the astute ability of cancer cells to adapt to their environment and to intracellular changes to achieve a single goal survival. The aberrant exosomal process in cancer represents yet another adaptation that promotes survival of cancer. Cancer cells can secrete more exosomes than healthy cells, but more importantly, the content of cancer cells is distinct. An illustrative distinction is that exosomes derived from cancer cells contain more microRNA than healthy cells and unlike exosomes released from healthy cells, this microRNA can be associated with the RNA-induced silencing complex (RISC) which is required for processing mature and biologically active microRNA. Cancer derived exosomes have the ability to transfer metastatic potential to a recipient cell and cancer exosomes function in the physical process of invasion. In this review we conceptualize the aberrant exosomal process (formation, content selection, loading, trafficking, and release) in cancer as being partially attributed to cancer specific differences in the endocytotic process of receptor recycling/degradation and plasma membrane remodeling and the function of the endosome as a signaling entity. We discuss this concept and, to advance comprehension of exosomal function in cancer as mediators of communication, we detail and discuss exosome biology, formation, and communication in health and cancer; exosomal content in cancer; exosomal biomarkers in cancer; exosome mediated communication in cancer metastasis, drug resistance, and interfacing with the immune system; and discuss the therapeutic manipulation of exosomal content for cancer treatment including current clinical trials of exosomal therapeutics. Often referred to as cellular nanoparticles, understanding exosomes, and how cancer cells use these cellular nanoparticles in communication is at the cutting edge frontier of advancing cancer biology. PMID- 26143225 TI - Postoperative steroid therapy for biliary atresia: Systematic review and meta analysis. AB - BACKGROUND/OBJECTIVES: Adjuvant steroid therapy has become popular in the postoperative management of biliary atresia. However, the benefits of steroid therapy are still not clear. We performed a systematic review and meta-analysis to determine the effect of steroids on bile drainage posthepatoportoenterostomy. METHODS: Studies published from 1968 to 2014 were searched from MEDLINE, EMBASE, Google scholar and Cochrane databases. A meta-analysis of randomized controlled trials (RCT) and observational studies comparing bile drainage between steroid and nonsteroid therapies posthepatoportoenterostomy was performed. RESULTS: Seven studies (2 RCTs and 5 observational studies) were included, comprising 259 cases of nonsteroid and 228 cases of steroid therapies. There was no statistical improvement in jaundice clearance in the steroid group [pooled odds ratio (OR)=1.51; 95% confidence interval (CI) 0.95-2.41; P=0.08; I(2)=30%]. Among 7 studies, 4 studies applied similar moderate high-dose steroid regimens (prednisolone 4-5mg/kg/day for 1-2 weeks followed by weeks of tapering dosage). However, these moderate high-dose regimens demonstrated improved jaundice clearance at 6 months posthepatoportoenterostomy (pooled OR=1.59; 95% CI 1.03 2.45; P=0.04; I(2)=0%). A subgroup analysis also showed that the effect of those moderate high-dose steroids was more pronounced in infants operated on by 70 days of age (pooled OR=1.86; 95% CI 1.08-3.22; P=0.03; I(2)=0%). CONCLUSION: Moderate high-dose steroid therapy improves jaundice clearance, especially for infants who undergo hepatoportoenterostomy by 70 days of age. However, more RCTs with longer follow-up are necessary to demonstrate the effect of steroids on the long-term outcomes of biliary atresia. PMID- 26143226 TI - Practice pattern variation in surgical management of pelvic organ prolapse and urinary incontinence in The Netherlands. AB - INTRODUCTION: Practice pattern variation (PPV) is the difference in care that cannot be explained by the underlying medical condition. The aim of this study was to describe PPV among Dutch gynecologists regarding treatment of pelvic organ prolapse (POP) and urinary incontinence (UI). MATERIALS AND METHODS: PPV was calculated from data of healthcare declaration codes of 2010. Data were provided by Vektis and Kiwa Carity. PPV for POP and UI in general was calculated per hospital and per region. Furthermore, PPV for transvaginal mesh and surgical treatment of uterine descent was assessed. RESULTS: PPV of surgical treatment for POP and UI in general was assessed for 91 hospitals. PPV for surgical treatment of uterine descent and transvaginal mesh placement was calculated for 88 hospitals. A high PPV per hospital and per region was found. In some hospitals, a hysterectomy was performed in all cases of uterovaginal prolapse, while in other hospitals, uterus-preserving techniques were mostly performed. A high PPV of transvaginal mesh placement was observed. CONCLUSION: In the small country of The Netherlands, we found a high PPV in surgical management of POP and UI with respect to the choice for surgical treatment and the type of surgery. This finding might be due to the absence of clearly defined guidelines. Studies with respect to conservative versus surgical treatment and the type of surgery are of need to establish evidence-based guidelines. PMID- 26143227 TI - A functional Bucky ball-GFP transgene visualizes germ plasm in living zebrafish. AB - In many animals, the germline is specified by maternal RNA-granules termed germ plasm. The correct localization of germ plasm during embryogenesis is therefore crucial for the specification of germ cells. In zebrafish, we previously identified Bucky ball (Buc) as a key regulator of germ plasm formation. Here, we used a Buc antibody to describe its continuous germ plasm localization. Moreover, we generated a transgenic Buc-GFP line for live imaging, which visualizes germ plasm from its assembly during oogenesis up to the larval stages. Live imaging of Buc-GFP generated stunning movies, as they highlighted the dynamic details of germ plasm movements. Moreover, we discovered that Buc was still detected in primordial germ cells 2 days after fertilization. Interestingly, the transgene rescued buc mutants demonstrating genetically that the Buc-GFP fusion protein is functional. These results show that Buc-GFP exerts all biochemical interactions essential for germline development and highlight the potential of this line to analyze the molecular regulation of germ plasm formation. PMID- 26143228 TI - Intestinal epithelial cell transported TLR2 ligand stimulates Ly6C+ monocyte differentiation in a G-CSF dependent manner. AB - Microflora-induced TLR signaling in the intestinal epithelium is essential for a proper intestinal barrier function. Because of the close interactions of this epithelial layer with underlying mononuclear phagocytes, we hypothesized that epithelial TLR signaling may affect the differentiation of myeloid cell populations. In in vitro cultures we observed that colonic epithelial monolayers actively transported TLR2 ligands towards their basolateral side. The transported TLR2 ligands strongly stimulated the development of Ly6C(+) monocytes, while dendritic cell differentiation was inhibited. The TLR2 effect on monocyte and dendritic cell differentiation was mediated by the production of G-CSF. Mice lacking TLR signaling and mice that were treated with antibiotics showed decreased numbers of Ly6C(+) monocytes in bone marrow and spleen, which points to a role for microbial derived TLR-ligands in the homeostasis of Ly6C(+) monocytes. In conclusion, our results indicate that TLR ligands that are transported by intestinal epithelial cells stimulate Ly6C(+) monocyte development and suggest that this process may be involved in the maintenance of systemic Ly6C(+) monocyte numbers. PMID- 26143229 TI - Biotransformation of aflatoxin B1 and aflatoxin G1 in peanut meal by anaerobic solid fermentation of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus. AB - The purpose of this study was to explore the ability of anaerobic solid fermentation of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus to biotransform aflatoxins in peanut meal. The pH of the peanut meal was adjusted above 10, and then heated for 10 min at 100 degrees C, 115 degrees C and 121 degrees C. The S. thermophilus and L. delbrueckii subsp. bulgaricus were precultured together in MRS broth for 48 h at 37 degrees C. The heated peanut meal was mixed with precultured MRS broth containing 7.0*10(8) CFU/mL of S. thermophilus and 3.0*10(3) CFU/mL of L. delbrueckii subsp. bulgaricus with the ratio of 1 to 1 (weight to volume) and incubated in anaerobic jars at 37 degrees C for 3 days. The aflatoxin content in the peanut meal samples was determined by HPLC. The results showed that the peanut meal contained mainly aflatoxin B1 (AFB1) (10.5+/-0.64 MUg/kg) and aflatoxin G1 (AFG1) (18.7+/-0.55 MUg/kg). When heat treatment was combined with anaerobic solid fermentation, the biotransformation rate of aflatoxins in peanut meal could attain 100%. The cytotoxicity of fermented peanut meal to L929 mouse connective tissue fibroblast cells was determined by MTT assay and no significant toxicity was observed in the fermented peanut meal. Furthermore, heat treatment and anaerobic solid fermentation did not change the amino acid concentrations and profile in peanut meal. PMID- 26143230 TI - A retrospective analysis of the impact of an obstetrician on delivery and care outcomes at four district hospitals in Ghana. PMID- 26143231 TI - Host ABC transporter proteins may influence the efficacy of ivermectin and possibly have broader implications for the development of resistance in parasitic nematodes. AB - ABC transporter proteins function to extrude compounds from the cell. These proteins present an obstacle for treatment and for overcoming drug resistance as they are expressed by both host and parasite, and function similarly. The contribution of host ABC proteins to drug efficacy was examined using ivermectin and a Brugia malayi model system. Parallel in vitro and in vivo experiments were conducted using equal concentrations of ivermectin. The motilities and fecundity of B. malayi exposed to ivermectin in vitro were significantly lower than those treated in vivo. The higher motilities were correlated with low concentrations of ivermectin in worms extracted from treated hosts. The expression of ABC proteins was significantly higher in worms treated in vitro compared to those treated in vivo as well as in gerbils treated with ivermectin than in non-treated controls. The results suggest that host ABC transporters may influence the efficacy of ivermectin. PMID- 26143232 TI - Layer-by-layer engineered nanocapsules of curcumin with improved cell activity. AB - Nanocarriers based on electrostatic Layer-by-layer (LbL) assembly of CaCO3 nanoparticles (CaCO3 NPs) was investigated. These inorganic nanoparticles was used as templates to construct nanocapsules made from films based on two oppositely charged polyelectrolytes, poly(diallyldimethylammonium chloride), and poly (sodium 4-styrene-sulfonate sodium salt), followed by core dissolution. The naked CaCO3 NPs, CaCO3 NPs coated with the polyelectrolytes and hollow nanocapsules were found with hexagonal shape with average sizes of 350-400 nm. A reversal of the surface charge between positive to negative zeta potential values was found, confirming the adsorption of polyelectrolytes. The loading efficiency and release of curcumin were controlled by the hydrophobic interactions between the drug and the polyelectrolyte matrix of the hollow nanocapsules. The quantity of curcumin released from hollow nanocapsules was found to increase under acidic environments, which is a desirable for anti-cancer drug delivery. The hollow nanocapsules were found to localize in the cytoplasm and nucleus compartment of Hela cancer cells after 24 h of incubation. Hollow nanocapsules were non-toxic to human fibroblast cells. Furthermore, curcumin loaded hollow nanocapsules exhibited higher in vitro cell inhibition against Hela cells than that of free curcumin, suggesting that polyelectrolyte based-hollow nanocapsules can be utilized as new carriers for drug delivery. PMID- 26143233 TI - Local delivery system of doxycycline hyclate based on epsilon-caprolactone copolymers for periodontitis treatment. AB - The aim of the study was to evaluate kinetics of doxycycline hyclate release from polymeric bioresorbable implants and to examine suitability of this system for local treatment of periodontitis. Selected trimethylene carbonate/epsilon caprolactone (TMC/CL) and glycolide/caprolactone (GL/CL) copolymers were synthesized and used as carriers in the form of small elastic rings with 5 wt% and 10 wt% doxycycline hyclate content, or in the form of flakes obtained through electro-spinning technique. The release of the drug under in vitro conditions has been tested. The study has shown that equimolar TMC/CL copolymer loaded with 10 wt% of doxycycline hyclate appears to be the most suitable copolymer for assumed system. The drug release proceeds mainly by diffusion of medium into the polymeric matrix and then the drug is washed out. Daily validation of doxycycline doses released by the system should ensure accurate course of the therapy. PMID- 26143234 TI - Methods of administering oral formulations and child acceptability. AB - INTRODUCTION: Children may be unable or unwilling to swallow medicines. In order to avoid or accommodate any such problems, parents may decide to administer medicines other than intended. The aim of this study was to investigate how parents administered four oral placebo formulations to infants and preschool children and how the applied methods correlated with child acceptability. METHODS: Parents were asked to administer a 4 mm mini-tablet, powder, suspension and syrup to their child twice on one day and to report the child characteristics and administration details in a participant diary. RESULTS: A 151 children were included. The tablet, syrup and suspension were mostly given on their own, whereas the powder was commonly given with food or drink. Generally, the higher the child acceptability (VAS-score) of the first administration of a specific formulation, the less frequently its method of administration was changed. A change in the method of administration of the same formulation involving (a larger quantity of) food or drink generally resulted in a higher VAS-score. CONCLUSIONS: The joint administration of medicines with food or drink is an effective strategy to ensure swallowing. This study supports earlier findings that 4mm mini-tablets are a suitable dosage form from infant age. PMID- 26143235 TI - Dissolved carbon dioxide and oxygen concentrations in purge of vacuum-packaged pork chops and the relationship to shelf life and models for estimating microbial populations. AB - The objectives of this study were to determine the dissolved CO2 and O2 concentrations in the purge of vacuum-packaged pork chops over a 60 day storage period, and to elucidate the relationship of dissolved CO2 and O2 to the microbial populations and shelf life. As the populations of spoilage bacteria increased, the dissolved CO2 increased and the dissolved O2 decreased in the purge. Lactic acid bacteria dominated the spoilage microflora, followed by Enterobacteriaceae and Brochothrix thermosphacta. The surface pH decreased to 5.4 due to carbonic acid and lactic acid production before rising to 5.7 due to ammonia production. A mathematical model was developed which estimated microbial populations based on dissolved CO2 concentrations. Scanning electron microscope images were also taken of the packaging film to observe the biofilm development. The SEM images revealed a two-layer biofilm on the packaging film that was the result of the tri-phase growth environment. PMID- 26143236 TI - Complications After TKA in Patients With Hemophilia or Von Willebrand's Disease. AB - Little is known about perioperative complications following total knee arthroplasty (TKA) in patients with bleeding disorders. This study utilized a national database to evaluate postoperative complication rates and up to 8-year revision rates after TKA in patients with hemophilia (n=3396) and von Willebrand's disease (n=1379) compared to a matched cohort of patients without a bleeding disorder (n=427,132 and n=394,657 respectively). Hemophilia and von Willebrand's disease were associated with significantly higher rates of infection, transfusion of blood products, medical complications, and revision after TKA compared to matched controls. Hemophilia was associated with significantly higher rates of venous thromboembolism and transfusion compared to patients with von Willebrand's disease and matched controls after TKA. PMID- 26143237 TI - Comparison of Wear and Oxidation in Retrieved Conventional and Highly Cross Linked UHMWPE Tibial Inserts. AB - Two groups of retrieved tibial inserts from one manufacturer's knee system were analyzed to evaluate the effect of a highly cross-linked bearing surface on wear and in vivo oxidation. The two groups ((1) conventional gamma-inert sterilized and (2) highly cross-linked, coupled with the same rough (Ra=0.25) Ti-6Al-4V tray) were matched with statistically similar in vivo duration and patient variables. The retrieved inserts were analyzed for ketone oxidation and wear in the form of dimensional change. The difference in oxidation rate between highly cross-linked and conventional gamma-inert sterilized inserts did not reach statistical significance. Observations suggest that the majority of wear can be accounted for by the backside interface with the rough Ti-6Al-4V tray; however, wear measured by thickness-change rate was statistically indistinguishable between the two bearing materials. PMID- 26143238 TI - Combining Concentrated Autologous Bone Marrow Stem Cells Injection With Core Decompression Improves Outcome for Patients with Early-Stage Osteonecrosis of the Femoral Head: A Comparative Study. AB - The management of early-stage osteonecrosis of the femoral head (ONFH) remains challenging. This study aimed to evaluate the effects of core decompression and concentrated bone marrow implantation on ONFH. The study recruited 28 hips with early ONFH randomly assigned into two groups of core decompression with (group A) and without (group B) bone marrow injection. Patients were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, Visual Analogue Scale (VAS) pain index, and MRI. The mean WOMAC and VAS scores in all patients improved significantly (P<0.001). MRI showed a significant improvement in group A (P=0.046) and significant worsening in group B (P<0.001). Bone marrow stem cell injection with core decompression can be effective in early ONFH. PMID- 26143241 TI - Infant Safe Sleep Interventions, 1990-2015: A Review. AB - Sleep-related infant deaths remain a major public health issue. Multiple interventions have been implemented in efforts to increase adherence to safe sleep recommendations. We conducted a systematic review of the international research literature to synthesize research on interventions to reduce the risk of sleep-related deaths and their effectiveness in changing infant sleep practices. We searched PubMed, CINAHL, PsycINFO, and Google Scholar for peer-reviewed articles published between 1990 and 2015 which described an intervention and reported results. Twenty-nine articles were included for review. Studies focused on infant caregivers, health care professionals, peers, and child care professionals. Targeted behaviors included sleep position, location, removing items from the crib, breastfeeding, smoke exposure, clothing, pacifier use, and knowledge of Sudden Infant Death Syndrome. Most articles described multi-faceted interventions, including: one-on-one or group education, printed materials, visual displays, videos, and providing resources such as cribs, pacifiers, wearable blankets, and infant t-shirts. Two described public education campaigns, one used an educative questionnaire, and one encouraged maternal note taking. Health professional interventions included implementing safe sleep policies, in service training, printed provider materials, eliciting agreement on a Declaration of Safe Sleep Practice, and sharing adherence data. Data collection methods included self-report via surveys and observational crib audits. Over half of the studies utilized comparison groups which helped determine effectiveness. Most articles reported some degree of success in changing some of the targeted behaviors; no studies reported complete adherence to recommendations. Future studies should incorporate rigorous evaluation plans, utilize comparison groups, and collect demographic and collect follow-up data. PMID- 26143239 TI - Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system. AB - Apelin and its G protein-coupled receptor (GPCR) have emerged as a key signalling pathway in the cardiovascular system. The peptide is a potent inotropic agent and vasodilator. Remarkably, a peptide, Elabela/Toddler, that has little sequence similarity to apelin, has been proposed as a second endogenous apelin receptor ligand and is encoded by a gene from a region of the genome previously classified as 'non-coding'. Apelin is downregulated in pulmonary arterial hypertension and heart failure. To replace the missing endogenous peptide, 'biased' apelin agonists have been designed that preferentially activate G protein pathways, resulting in reduced beta-arrestin recruitment and receptor internalisation, with the additional benefit of attenuating detrimental beta-arrestin signalling. Proof of-concept studies support the clinical potential for apelin receptor biased agonists. PMID- 26143242 TI - The giant panda gut microbiome. AB - Giant pandas (Ailuropoda melanoleuca) are bamboo specialists that evolved from carnivores. Their gut microbiota probably aids in the digestion of cellulose and this is considered an example of gut microbiota adaptation to a bamboo diet. However, this issue remains unresolved and further functional and compositional studies are needed. PMID- 26143243 TI - The Toll/NF-kappaB pathway in cuttlefish symbiotic accessory nidamental gland. AB - The female genital apparatus of decapod cephalopods contains a symbiotic accessory nidamental gland (ANG) that harbors bacterial symbionts. Although the ANG bacterial consortium is now well described, the impact of symbiosis on Sepia officinalis innate immunity pathways remains unknown. In silico analysis of the de novo transcriptome of ANG highlighted for the first time the existence of the NF-kappaB pathway in S. officinalis. Several signaling components were identified, i.e. five Toll-like receptors, eight signaling cascade features, and the immune response target gene iNOS, previously described as being involved in the initiation of bacterial symbiosis in a cephalopod gland. This work provides a first key for studying bacterial symbiosis and its impact on innate immunity in S. officinalis ANG. PMID- 26143240 TI - Peptidomics for the discovery and characterization of neuropeptides and hormones. AB - The discovery of neuropeptides as signaling molecules with paracrine or hormonal regulatory functions has led to trailblazing advances in physiology and fostered the characterization of numerous neuropeptide-binding G protein-coupled receptors (GPCRs) as potential drug targets. The impact on human health has been tremendous: approximately 30% of commercial drugs act via the GPCR pathway. However, about 25% of the GPCRs encoded by the mammalian genome still lack their pharmacological identity. Searching for the orphan GPCR endogenous ligands that are likely to be neuropeptides has proved to be a formidable task. Here we describe the mass spectrometry (MS)-based technologies and experimental strategies that have been successful in achieving high-throughput characterization of endogenous peptides in nervous and endocrine systems. PMID- 26143244 TI - Predictors of Clinical Outcome of Assertive Community Treatment (ACT) in a Rural Area in Denmark: An Observational Study with a Two-Year Follow-Up. AB - Assertive Community Treatment (ACT) is a multidisciplinary team approach to community care treatment, mainly characterised by small caseload and individualised care. The aim of the present study was to identify predictors of clinical outcome in ACT using an observational design. Three ACT Teams were established in The North Denmark Region to treat patients with severe mental illness. The patients were identified and followed in regional and national psychiatric registers, and in social and somatic case registers, 2 years before and 2 years after inclusion. The results showed that the use of psychiatric hospital services decreased significantly for the 240 included patients. Furthermore, the psychopharmacological profile was improved. No significant change occurred in the consumption of the somatic hospitals. Clinical outcome, defined as halving of admissions or bed days, was in a logistic analysis predicted by the patient's psychiatric use of inpatient service prior to inclusion in an ACT Team. PMID- 26143245 TI - Impact of inappropriate lymphadenectomy on lung metastasectomy for patients with metastatic colorectal cancer. AB - PURPOSE: To evaluate the characteristics of lymph node assessment in the Spanish Colorectal Metastasectomy Registry (GECMP-CCR) and to analyze and compare the survival of patients with pathological absence or presence of lymph node metastases (LNM) with the survival of those with uncertain lymph node status (uLNs). METHODS: A total of 522 patients with lung metastases from colorectal carcinoma were prospectively registered from 2008 to 2010. To confirm the pathologic absence of LNM, systematic nodal dissection or systematic sampling was required, or the lymph node status was coded as uncertain. Disease-specific survival and disease-free survival were calculated by the Kaplan-Meier method with the log-rank test for comparisons. RESULTS: Lymphadenectomy was performed in 250 (48%) patients. LNM was found in 25 (10%) of the patients who had lymph node assessment done. The 3- and 5-year disease-specific survival rates according to lymph node status were 73.5 and 58.3% in the absence of LNM, 50.5 and 24.8% when LNM was confirmed, and 69 and 44% for those with uLNs, respectively (p = 0.006). CONCLUSIONS: The presence of LNM and uLNs is associated with an increased risk of death. The association of nodal assessment at the time of metastasectomy to identify LNM helps us to refine the postoperative prognosis; therefore, its impact should be properly studied in a prospective clinical trial. PMID- 26143246 TI - Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity. AB - Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network. PMID- 26143247 TI - Demographic Differences in PrEP-Related Stereotypes: Implications for Implementation. AB - Qualitative interviews about pre-exposure prophylaxis (PrEP) stereotypes were conducted with a subsample of 160 MSM who participated in a PrEP messaging study. Negative stereotypes about PrEP users were identified by 80 % of participants. Two types of stereotypes were most common: PrEP users are HIV-infected (and lying about it), and PrEP users are promiscuous and resistant to condom use. Participants' identification of these stereotype categories differed significantly by demographic factors (i.e., race/ethnicity, education). Expanding access to PrEP requires recognizing potential differences in the experience or anticipation of PrEP-related stereotypes that might impact willingness to discuss PrEP with providers, friends, or partners. PMID- 26143248 TI - Gender Differences in Psychosocial Factors Associated with HIV Viral Suppression Among African-American Injection Drug Users. AB - Research suggests gender differences exist in achieving undetectable viral load (UVL) among persons living with HIV (PLHIV), and that psychosocial health factors may play a role. The present study examined these factors among African-American PLHIV enrolled in the BEACON study. Participants completed self-report surveys and gave biomarker data. Poisson regression with robust standard errors was implemented. Men with moderate religious activity had 1.3 times the likelihood of UVL as men with low religious activity (p < 0.10; N = 199). Men with 1-2 mental illness diagnoses had 1.3 times the likelihood of UVL as men with none (p < 0.05). Women using 1-2 substances had 28 % lower likelihood of UVL than non-using women (N = 122; p < 0.10). Finally, women with frequent doctor-patient communication had 35 % higher likelihood of UVL as women with less doctor-patient communication (p < 0.05). Results suggest that social support, substance use, and mental illness function differently among men and women. Healthcare professionals should employ gender-specific interventions to address and improve HIV health outcomes. PMID- 26143249 TI - Novel and Recently Evolved MicroRNA Clusters Regulate Expansive F-BOX Gene Networks through Phased Small Interfering RNAs in Wild Diploid Strawberry. AB - The wild strawberry (Fragaria vesca) has recently emerged as an excellent model for cultivated strawberry (Fragaria * ananassa) as well as other Rosaceae fruit crops due to its short seed-to-fruit cycle, diploidy, and sequenced genome. Deep sequencing and parallel analysis of RNA ends were used to identify F. vesca microRNAs (miRNAs) and their target genes, respectively. Thirty-eight novel and 31 known miRNAs were identified. Many known miRNAs targeted not only conserved mRNA targets but also developed new target genes in F. vesca. Significantly, two new clusters of miRNAs were found to collectively target 94 F-BOX (FBX) genes. One of the miRNAs in the new cluster is 22 nucleotides and triggers phased small interfering RNA production from six FBX genes, which amplifies the silencing to additional FBX genes. Comparative genomics revealed that the main novel miRNA cluster evolved from duplications of FBX genes. Finally, conserved trans-acting siRNA pathways were characterized and confirmed with distinct features. Our work identified novel miRNA-FBX networks in F. vesca and shed light on the evolution of miRNAs/phased small interfering RNA networks that regulate large gene families in higher plants. PMID- 26143250 TI - Histone H2B Monoubiquitination Mediated by HISTONE MONOUBIQUITINATION1 and HISTONE MONOUBIQUITINATION2 Is Involved in Anther Development by Regulating Tapetum Degradation-Related Genes in Rice. AB - Histone H2B monoubiquitination (H2Bub1) is an important regulatory mechanism in eukaryotic gene transcription and is essential for normal plant development. However, the function of H2Bub1 in reproductive development remains elusive. Here, we report rice (Oryza sativa) HISTONE MONOUBIQUITINATION1 (OsHUB1) and OsHUB2, the homologs of Arabidopsis (Arabidopsis thaliana) HUB1 and HUB2 proteins, which function as E3 ligases in H2Bub1, are involved in late anther development in rice. oshub mutants exhibit abnormal tapetum development and aborted pollen in postmeiotic anthers. Knockout of OsHUB1 or OsHUB2 results in the loss of H2Bub1 and a reduction in the levels of dimethylated lysine-4 on histone 3 (H3K4me2). Anther transcriptome analysis revealed that several key tapetum degradation-related genes including OsC4, rice Cysteine Protease1 (OsCP1), and Undeveloped Tapetum1 (UDT1) were down-regulated in the mutants. Further, chromatin immunoprecipitation assays demonstrate that H2Bub1 directly targets OsC4, OsCP1, and UDT1 genes, and enrichment of H2Bub1 and H3K4me2 in the targets is consistent to some degree. Our studies suggest that histone H2B monoubiquitination, mediated by OsHUB1 and OsHUB2, is an important epigenetic modification that in concert with H3K4me2, modulates transcriptional regulation of anther development in rice. PMID- 26143251 TI - HISTONE DEACETYLASE6-Defective Mutants Show Increased Expression and Acetylation of ENHANCER OF TRIPTYCHON AND CAPRICE1 and GLABRA2 with Small But Significant Effects on Root Epidermis Cellular Pattern. AB - Cellular patterning in the Arabidopsis (Arabidopsis thaliana) root epidermis is dependent on positional information, the transmission of which involves histone acetylation. Here, we report that HISTONE DEACETYLASE6 (HDA6) has significant effects on this cellular patterning. Mutation of HDA6 led to ectopic hair cells in the nonhair positions of root epidermis in Arabidopsis, based on an analysis of paraffin sections stained with Toluidine Blue. While HDA6 was present throughout the root tip, epidermis-specific complementation with HDA6 could rescue the hda6 phenotype. Both transcript levels and expression patterns of ENHANCER OF TRIPTYCHON AND CAPRICE1 (ETC1) and GLABRA2 (GL2) in the root tip were affected in hda6. Consistent with these changes in expression, HDA6 directly bound to the promoter regions of ETC1 and GL2, and acetylation of histone H3 on these promoter regions and acetylation of histone H4 on the ETC1 promoter region was increased in the hda6 mutant. Taken together, these results indicate that HDA6 affects the cellular patterning of Arabidopsis root epidermis through altering the histone acetylation status of ETC1 and GL2 promoters and thereby affects the expression of these two components of the core transcription factor network determining epidermal cell fates. Our findings thus provide new insights into the role of histone acetylation in root epidermis cell patterning. PMID- 26143253 TI - Genome-Wide Nucleosome Occupancy and Positioning and Their Impact on Gene Expression and Evolution in Plants. AB - The fundamental unit of chromatin is the nucleosome that consists of a protein octamer composed of the four core histones (Hs; H3, H4, H2A, and H2B) wrapped by 147 bp of DNA. Nucleosome occupancy and positioning have proven to be dynamic and have a critical impact on expression, regulation, and evolution of eukaryotic genes. We developed nucleosome occupancy and positioning data sets using leaf tissue of rice (Oryza sativa) and both leaf and flower tissues of Arabidopsis (Arabidopsis thaliana). We show that model plant and animal species share the fundamental characteristics associated with nucleosome dynamics. Only 12% and 16% of the Arabidopsis and rice genomes, respectively, were occupied by well positioned nucleosomes. The cores of positioned nucleosomes were enriched with G/C dinucleotides and showed a lower C->T mutation rate than the linker sequences. We discovered that nucleosomes associated with heterochromatic regions were more spaced with longer linkers than those in euchromatic regions in both plant species. Surprisingly, different nucleosome densities were found to be associated with chromatin in leaf and flower tissues in Arabidopsis. We show that deep MNase-seq data sets can be used to map nucleosome occupancy of specific genomic loci and reveal gene expression patterns correlated with chromatin dynamics in plant genomes. PMID- 26143252 TI - The Arabidopsis Mediator Complex Subunit16 Is a Key Component of Basal Resistance against the Necrotrophic Fungal Pathogen Sclerotinia sclerotiorum. AB - Although Sclerotinia sclerotiorum is a devastating necrotrophic fungal plant pathogen in agriculture, the virulence mechanisms utilized by S. sclerotiorum and the host defense mechanisms against this pathogen have not been fully understood. Here, we report that the Arabidopsis (Arabidopsis thaliana) Mediator complex subunit MED16 is a key component of basal resistance against S. sclerotiorum. Mutants of MED16 are markedly more susceptible to S. sclerotiorum than mutants of 13 other Mediator subunits, and med16 has a much stronger effect on S. sclerotiorum-induced transcriptome changes compared with med8, a mutation not altering susceptibility to S. sclerotiorum. Interestingly, med16 is also more susceptible to S. sclerotiorum than coronatine-insensitive1-1 (coi1-1), which is the most susceptible mutant reported so far. Although the jasmonic acid (JA)/ethylene (ET) defense pathway marker gene PLANT DEFENSIN1.2 (PDF1.2) cannot be induced in either med16 or coi1-1, basal transcript levels of PDF1.2 in med16 are significantly lower than in coi1-1. Furthermore, ET-induced suppression of JA activated wound responses is compromised in med16, suggesting a role for MED16 in JA-ET cross talk. Additionally, MED16 is required for the recruitment of RNA polymerase II to PDF1.2 and OCTADECANOID-RESPONSIVE ARABIDOPSIS ETHYLENE/ETHYLENE RESPONSIVE FACTOR59 (ORA59), two target genes of both JA/ET-mediated and the transcription factor WRKY33-activated defense pathways. Finally, MED16 is physically associated with WRKY33 in yeast and in planta, and WRKY33-activated transcription of PDF1.2 and ORA59 as well as resistance to S. sclerotiorum depends on MED16. Taken together, these results indicate that MED16 regulates resistance to S. sclerotiorum by governing both JA/ET-mediated and WRKY33 activated defense signaling in Arabidopsis. PMID- 26143254 TI - A Universal Positive-Negative Selection System for Gene Targeting in Plants Combining an Antibiotic Resistance Gene and Its Antisense RNA. AB - Gene targeting (GT) is a useful technology for accurate genome engineering in plants. A reproducible approach based on a positive-negative selection system using hygromycin resistance and the diphtheria toxin A subunit gene as positive and negative selection markers, respectively, is now available. However, to date, this selection system has been applied exclusively in rice (Oryza sativa). To establish a universally applicable positive-negative GT system in plants, we designed a selection system using a combination of neomycin phosphotransferaseII (nptII) and an antisense nptII construct. The concomitant transcription of both sense and antisense nptII suppresses significantly the level of expression of the sense nptII gene, and transgenic calli and plants become sensitive to the antibiotic geneticin. In addition, we were able to utilize the sense nptII gene as a positive selection marker and the antisense nptII construct as a negative selection marker for knockout of the endogenous rice genes Waxy and 33-kD globulin through GT, although negative selection with this system is relatively less efficient compared with diphtheria toxin A subunit. The approach developed here, with some additional improvements, could be applied as a universal selection system for the enrichment of GT cells in several plant species. PMID- 26143255 TI - DNA Methylation within Transcribed Regions. AB - DNA methylation within transcribed genes is commonly found in diverse animals and plants. Here, we provide an overview of recent advances and the remaining mystery regarding intragenic DNA methylation. PMID- 26143256 TI - A family of DNA aptamers with varied duplex region length that forms complexes with thrombin and prothrombin. AB - Structural properties determine binding affinities of DNA aptamers specific to thrombin. Our paper is the first to focus on a family of eight G-quadruplex-based aptamers with varied duplex region length (from two to eight base pairs). We have shown that the duplex, which is not the main binding domain, greatly influences the interaction with thrombin and prothrombin. Furthermore, the affinity of an aptamer to thrombin and prothrombin increases (respectively from 2.7*10-8 M to 5.6*10-10 M and from 1.8*10-5 M to 7.1*10-9 M) with an increase in the number of nucleotide pairs in the duplex region. PMID- 26143257 TI - Kindlin-2 interacts with alpha-actinin-2 and beta1 integrin to maintain the integrity of the Z-disc in cardiac muscles. AB - Kindlin-2, as an integrin-interacting protein, was known to be required for the maintenance of cardiac structure and function in zebrafish. However, the mechanism remains unclear. We found that Kindlin-2 interacts and colocalizes with alpha-actinin-2 at the Z-disc of mouse cardiac muscles and there Kindlin-2 also interacts with beta1 integrin. Knockdown of Kindlin-2 influences the association of beta1 integrin with alpha-actinin-2 and disrupts the structure of the Z-disc and leads to cardiac dysfunction. Our data indicated that Kindlin-2 is a novel alpha-actinin-2-interacting protein and plays an important role in the regulation of cardiac structure and function. PMID- 26143258 TI - Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53 Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage. AB - Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro inflammatory cytokines, especially interleukin-1beta (IL-1beta). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH. PMID- 26143260 TI - S6K Promotes Dopaminergic Neuronal Differentiation Through PI3K/Akt/mTOR Dependent Signaling Pathways in Human Neural Stem Cells. AB - It has recently been reported that the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway regulates neuronal differentiation of neural stem cells (NSCs) derived from rats or mice and is essential for the self-renewal of human embryonic stem cells (hESCs). However, the roles of PI3K/Akt/mTOR signaling pathways during proliferation and dopaminergic neuronal differentiation of human neural stem cells (hNSCs) are poorly understood. In this study, we examined the effect of regulation of these intracellular signaling pathways in hNSCs on the potential to maintain proliferation and induce dopaminergic neuronal differentiation. Dopaminergic neuronal differentiation depended on the concentration of insulin in our culture system. Inhibition of PI3K/Akt with LY294002 reduced proliferation and inhibited dopaminergic neuronal differentiation of these cells. We also found that rapamycin, a specific inhibitor of mTOR, significantly reduced neuronal differentiation without affecting proliferation. Inhibition of the Akt/mTOR signaling pathway led to inhibition of p70 ribosomal S6 kinase (S6K) signaling, which reduced dopaminergic neuronal differentiation in hNSCs. Inhibition of S6K by a specific chemical inhibitor, PF-4708671 inhibited dopaminergic neuronal differentiation of hNSCs. As expected, transduction with a dominant negative S6K1 (S6K1-DN) construct impaired dopaminergic neuronal differentiation of hNSCs. Conversely, overexpression of constitutively active S6K1 (S6K1-CA) promoted dopaminergic neuronal differentiation of these cells. In a survival study, 4 weeks after transplantation, no or very few donor cells were viable in striata grafted with S6K1-DN-transduced hNSCs. In contrast, S6K1-CA-transduced hNSCs survived, integrated into striata to generate tubular masses of grafts and differentiated toward TH-positive cells. Taken together, these data demonstrated that insulin promotes dopaminergic neuronal differentiation through a PI3K/Akt/mTOR-dependent pathway and that S6K plays a critical role in dopaminergic neuronal differentiation in hNSCs. PMID- 26143262 TI - Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters. AB - In the present investigation, Quality by Design (QbD) approach was applied on the development and optimization of solid lipid nanoparticle (SLN) formulation of hydrophilic drug rivastigmine (RHT). RHT SLN were formulated by homogenization and ultrasonication method using Compritol 888 ATO, tween-80 and poloxamer-188 as lipid, surfactant and stabilizer respectively. The effect of independent variables (X1 - drug: lipid ratio, X2 - surfactant concentration and X3 - homogenization time) on quality attributes of SLN i.e. dependent variables (Y1 - size, Y2 - PDI and Y3 - %entrapment efficiency (%EE)) were investigated using 3(3) factorial design. Multiple linear regression analysis and ANOVA were employed to indentify and estimate the main effect, 2FI, quadratic and cubic effect. Optimized RHT SLN formula was derived from an overlay plot on which further effect of probe sonication was evaluated. Final RHT SLN showed narrow size distribution (PDI- 0.132+/-0.016) with particle size of 82.5+/-4.07 nm and %EE of 66.84+/-2.49. DSC and XRD study showed incorporation of RHT into imperfect crystal lattice of Compritol 888 ATO. In comparison to RHT solution, RHT SLN showed higher in-vitro and ex-vivo diffusion. The diffusion followed Higuchi model indicating drug diffusion from the lipid matrix due to erosion. Histopathology study showed intact nasal mucosa with RHT SLN indicating safety of RHT SLN for intranasal administration. PMID- 26143261 TI - The Association of Palmitoylethanolamide with Luteolin Decreases Autophagy in Spinal Cord Injury. AB - Spinal cord injury (SCI) is a devastating condition of the central nervous system (CNS) often resulting in severe functional impairment and for which there are not yet restorative therapies. In the present study, we performed a widely used model of SCI to determine the neuroprotective propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a flavonoid luteolin (Lut), given as a co ultramicronized compound co-ultraPEALut. In particular, by western blot analysis and immunofluorescence staining, we investigated whether this compound (at the dose of 1 mg/kg) was able to modulate autophagy. Our results showed that treatment with co-ultraPEALut after SCI reduced the expression of proteins promoter of autophagy such as Beclin-1 and microtubule-associated protein 1A/1B light chain 3 (MAP-LC3). In contrast, this compound decreased the levels of mammalian target of rapamycin (mTOR), p-Akt, and p-70S6K which are proteins that inhibit autophagy. These data confirmed that the protective role of co ultraPEALut is associated with inhibition of excessive autophagy and regulation of protein degradation. Therefore, treatment with co-ultraPEALut could be considered as a possible therapeutic approach in an acute traumatic lesion like SCI. PMID- 26143259 TI - Dissecting the Contribution of Vascular Alterations and Aging to Alzheimer's Disease. AB - Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline that afflicts as many as 45 % of individuals who survive past the age of 85. AD has been associated with neurovascular dysfunction and brain accumulation of amyloid-beta peptide, as well as tau phosphorylation and neurodegeneration, but the pathogenesis of the disease is still somewhat unclear. According to the amyloid cascade hypothesis of AD, accumulation of amyloid-beta peptide (Abeta) aggregates initiates a sequence of events leading to neuronal injury and loss, and dementia. Alternatively, the vascular hypothesis of AD incorporates the vascular contribution to the disease, stating that a primary insult to brain microcirculation (e.g., stroke) not only contributes to amyloidopathy but initiates a non-amyloidogenic pathway of vascular-mediated neuronal dysfunction and injury, which involves blood-brain barrier compromise, with increased permeability of blood vessels, leakage of blood-borne components into the brain, and, consequently, neurotoxicity. Vascular dysfunction also includes a diminished brain capillary flow, causing multiple focal ischemic or hypoxic microinjuries, diminished amyloid-beta clearance, and formation of neurotoxic oligomers, which lead to neuronal dysfunction. Here we present and discuss relevant findings on the contribution of vascular alterations during aging to AD, with the hope that a better understanding of the players in the "orchestra" of neurodegeneration will be useful in developing therapies to modulate the "symphony". PMID- 26143263 TI - Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions. AB - Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-kappaB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0+/-3.3 MUm and regular surface, zeta potential of -13.4+/-5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-kappaB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-alpha, IL-1beta, and TGF-beta, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1beta. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects. PMID- 26143265 TI - An Evidence-Based Review of Alternating Electric Fields Therapy for Malignant Gliomas. AB - OPINION STATEMENT: Glioblastoma is a deadly disease and even aggressive neurosurgical resection followed by radiation and chemotherapy only extends patient survival to a median of 1.5 years. The challenge in treating this type of tumor stems from the rapid proliferation of the malignant glioma cells, the diffuse infiltrative nature of the disease, multiple activated signal transduction pathways within the tumor, development of resistant clones during treatment, the blood brain barrier that limits the delivery of drugs into the central nervous system, and the sensitivity of the brain to treatment effect. Therefore, new therapies that possess a unique mechanism of action are needed to treat this tumor. Recently, alternating electric fields, also known as tumor treating fields (TTFields), have been developed for the treatment of glioblastoma. TTFields use electromagnetic energy at an intermediate frequency of 200 kHz as a locoregional intervention and act to disrupt tumor cells as they undergo mitosis. In a phase III clinical trial for recurrent glioblastoma, TTFields were shown to have equivalent efficacy when compared to conventional chemotherapies, while lacking the typical side effects associated with chemotherapies. Furthermore, an interim analysis of a recent clinical trial in the upfront setting demonstrated superiority to standard of care cytotoxic chemotherapy, most likely because the subjects' tumors were at an earlier stage of clonal evolution, possessed less tumor-induced immunosuppression, or both. Therefore, it is likely that the efficacy of TTFields can be increased by combining it with other anti-cancer treatment modalities. PMID- 26143264 TI - Safety and immunologic correlates of Melanoma GVAX, a GM-CSF secreting allogeneic melanoma cell vaccine administered in the adjuvant setting. AB - BACKGROUND: Limited adjuvant treatment options exist for patients with high-risk surgically resected melanoma. This first-in-human study investigated the safety, tolerability and immunologic correlates of Melanoma GVAX, a lethally irradiated granulocyte-macrophage colony stimulating factor (GM-CSF)-secreting allogeneic whole-cell melanoma vaccine, administered in the adjuvant setting. METHODS: Patients with stage IIB-IV melanoma were enrolled following complete surgical resection. Melanoma GVAX was administered intradermally once every 28 days for four cycles, at 5E7 cells/cycle (n = 3), 2E8 cells/cycle (n = 9), or 2E8 cells/cycle preceded by cyclophosphamide 200 mg/m(2) to deplete T regulatory cells (Tregs; n = 8). Blood was collected before each vaccination and at 4 and 6 months after treatment initiation for immunologic studies. Vaccine injection site biopsies and additional blood samples were obtained 2 days after the 1st and 4th vaccines. RESULTS: Among 20 treated patients, 18 completed 4 vaccinations. Minimal treatment-related toxicity was observed. One patient developed vitiligo and patches of white hair during the treatment and follow-up period. Vaccine site biopsies demonstrated complex inflammatory infiltrates, including significant increases in eosinophils and PD-1+ lymphocytes from cycle 1 to cycle 4 (P < 0.05). Serum GM-CSF concentrations increased significantly in a dose-dependent manner 48 h after vaccination (P = 0.0086), accompanied by increased numbers of activated circulating monocytes (P < 0.0001) and decreased percentages of myeloid derived suppressor cells among monocytes (CD14+ , CD11b+ , HLA-DR low or negative; P = 0.002). Cyclophosphamide did not affect numbers of circulating Tregs. No significant changes in anti-melanoma immunity were observed in peripheral T cells by interferon-gamma ELIPSOT, or immunoglobulins by serum Western blotting. CONCLUSION: Melanoma GVAX was safe and tolerable in the adjuvant setting. Pharmacodynamic testing revealed complex vaccine site immune infiltrates and an immune-reactive profile in circulating monocytic cell subsets. These findings support the optimization of Melanoma GVAX with additional monocyte and dendritic cell activators, and the potential development of combinatorial treatment regimens with synergistic agents. TRIAL REGISTRATION: NCT01435499. PMID- 26143266 TI - Secondary Adult Acute Myeloid Leukemia: a Review of Our Evolving Understanding of a Complex Disease Process. AB - OPINION STATEMENT: Secondary AML (s-AML) encompasses AML evolving from myelodysplasia (AML-MDS) and treatment-related AML (t-AML) after exposure to chemotherapy, radiation, or environmental toxins. S-AML has traditionally been considered a devastating disease, affecting a vulnerable population of heavily pretreated, older adults. A limited understanding of disease pathogenesis/heterogeneity and lack of effective treatments have hampered overall improvements in patient outcomes. With the recent understanding that the secondary nature of sAML does not by itself incur a poor prognosis and incorporation of cytogenetics and molecular genetics into patient care and the advancement of treatment, including improved supportive care, novel chemotherapeutics agents, and nonmyeloablative conditioning regimens as part of allogeneic hematopoietic cell transplantation (HCT), modest gains in survival and quality of life are beginning to be seen among patients with s-AML. PMID- 26143267 TI - The Role of Glucose Modulation and Dietary Supplementation in Patients With Central Nervous System Tumors. AB - OPINION STATEMENT: Central nervous system gliomas are the most common primary brain tumor, and these are most often high-grade gliomas. Standard therapy includes a combination of surgery, radiation, and chemotherapy which provides a modest increase in survival, but virtually, no patients are cured, the overall prognosis remains poor, and new therapies are desperately needed. Tumor metabolism is a well-recognized but understudied therapeutic approach to treating cancers. Dietary and nondietary modulation of glucose homeostasis and the incorporation of dietary supplements and other natural substances are potentially important interventions to affect cancer cell growth, palliate symptoms, reduce treatment-associated side effects, and improve the quality and quantity of life in patients with cancer. These approaches are highly desired by patients. However, they can be financially burdensome, associated with toxicities, and have, on occasion, reduced the efficacy of proven therapies and negatively impacted patient outcomes. The lack of rigorous scientific data evaluating almost all diet and supplement-based therapies currently limits their incorporation into standard oncologic practice. Rigorous studies are needed to document and improve these potentially useful approaches in patients with brain and other malignancies. PMID- 26143268 TI - Managing Disease and Therapy-Related Complications in Patients with Central Nervous System Tumors. AB - OPINION STATEMENT: Treating patients with brain tumors can be divided into tumor directed therapies, the management of tumor-related symptoms and complications and the psychosocial aspect of patient care. In this review, we will discuss the management of disease and treatment-related complications, which can negatively impact patient quality of life and functional status. Brain edema is a common complication or brain tumors and often causes more symptoms than the tumor itself. Treatment options are limited to the use of corticosteroids, which although effective have a plethora of side effects, so the goal should be the lowest dose that maximizes symptoms. Seizures are more common in lower grade brain tumors and treatment should be limited to patients who have seizures using agents that do not affect the metabolism of other drugs, especially chemotherapies. Blood clots are also common in patients and although there is a "fear" of tumoral bleeding, this is not a frequent occurrence; hence, using anticoagulants should be routinely used in patients who experience this complication. PMID- 26143269 TI - Current Management and Treatment Modalities for Intramedullary Spinal Cord Tumors. AB - OPINION STATEMENT: Intramedullary spinal cord tumors are rare central nervous system tumors with unique challenges due to the eloquence of the surrounding tissue. Their treatment and prognosis is largely dependent on tumor histology and patient functionality. The introduction and advancement of microsurgical techniques have made surgery the mainstay of treatment for intramedullary tumors. Tumors that are well demarcated (e.g., ependymomas, hemangioblastomas) can be resected for cure, while more infiltrative tumors (e.g., high-grade astrocytomas) are typically managed with biopsies or limited resections in order to minimize the significant risk of damage to the spinal cord. The use of more aggressive surgical resection for astrocytoma is controversial but may have an increasing role in select cases. The use of intraoperative neurophysiologic monitoring and intraoperative ultrasound may help guide the extent of surgery while minimizing damage to normal tissue. Advances in MRI technology have greatly aided the diagnosis and preoperative planning of intramedullary tumors. Further advances in intraoperative MRI may make this a useful tool in guiding extent of resection. Preoperative functional status is the most important predictor of neurologic outcome, while histology and extent of resection are the most important predictors of progression-free survival. The use of adjuvant radiation and chemotherapy is dependent on patient age and histology but is largely reserved for high-grade tumor histologies or systemic involvement. Children are particularly at risk of radiation-induced injury, and these cases may benefit from more focused stereotactic radiation where necessary. Further studies are needed to support new surgical strategies minimizing destabilization and to investigate new forms of adjuvant therapy to minimize toxicity. PMID- 26143270 TI - Bromate formation in bromide-containing water through the cobalt-mediated activation of peroxymonosulfate. AB - Bromate formation in bromide-containing water through the cobalt (Co)-mediated activation of peroxymonosulfate (PMS) was investigated. Increasing the PMS dosage and the cobalt dosage increased the formation of bromate and bromate yields of up to 100% were recorded under the test conditions. The bromate yield increased to a maximum as the pH rose from 2.7 to 6 before decreasing by over 90% as the pH rose further from 6 to above 9. The bromate formation is a two-step process involving free bromine as a key intermediate and bromate as the final product. In the first step, apart from the known oxidation of bromide to free bromine and of free bromine to bromate by sulfate radicals (SO4(-)), Co(III) produced from the oxidation of Co(II) by PMS and SO4(-) also oxidizes bromide to free bromine. The contribution of Co(III) to the bromate formation was verified with the addition of methanol and EDTA, a radical scavenger and a Co(III) ligand, respectively. In the presence of methanol, free bromine formation increased with increasing Co(II) dosage but no bromate was detected, indicating that Co(III) oxidized bromide to form free bromine but not bromate. In the presence of both EDTA and methanol, no free bromine or bromate was detected, as Co(III) was stabilized by EDTA to form the Co(III)EDTA(-) complex, which could not oxidize bromide. Mathematical simulation further suggested that Co(III) outweighed SO4(-) to oxidize bromide to free bromine. On the other hand, SO4(-) is essential for the oxidation of free bromine to bromate in the second step. In real water, the presence of NOM significantly decreased the bromate formation but caused the brominated organic DBP formation with high quantity. This is the first study to demonstrate the significant bromate formation in the Co/PMS system and the substantial contribution of Co(III) to the formation. PMID- 26143271 TI - Chronic effects of temperature and nitrate pollution on Daphnia magna: Is this cladoceran suitable for widespread use as a tertiary treatment? AB - Effluent clarification and disinfection are major challenges in wastewater management. The cladoceran Daphnia magna has been proposed as a cost-effective and ecosystem-friendly option to clarify and disinfect secondary effluents, but its efficacy has not been fully tested under different sewage conditions. The present study explores the effects of temperature and nitrate on the efficacy of D. magna as a tertiary treatment at two different scales (individual assays and microcosms). Individual assays were employed to determine direct effects of temperature and/or nitrate on D. magna cultured in a suspension of organic matter. Using microcosms under the same environmental conditions, we explored the clearing efficacy of D. magna interacting with a natural microbial community. Individual assays revealed that D. magna mortality increased by 17% at 26 degrees C, 21% at >250 mg NO3(-)/l and by 60% at 26 degrees C and at >250 mg NO3(-)/l, and individuals displayed reduced body size, filtering rates and fecundity when compared to those at 21 degrees C and <40 mg NO3(-)/l. Improved performance under these conditions was also mirrored in the microcosms, with a higher density of D. magna (>100 ind/l) at 21 degrees C and <40 mg NO3(-)/l compared to the number (0-21 ind/l) at 26 degrees C and/or >250 mg NO3(-)/l. In the microcosms at 21 degrees C and <40 mg NO3(-)/l, turbidity and the density of bacteria, protists and micro-metazoa decreased in relation to those at 26 degrees C and/or >250 mg NO3(-)/l. Each treatment developed a unique and characteristic microbial assemblage, and D. magna was identified as the major driver of the community structure of protists and micro-metazoa. This enabled us to determine taxa vulnerability to D. magna grazing, and to re-define their tolerance thresholds for nitrate. In conclusion, this study increases our knowledge of how microbes respond to temperature and nitrate pollution, and highlights that D. magna efficacy as a tertiary treatment can be seriously compromised by variable environmental conditions. PMID- 26143272 TI - Modeling the inactivation of ascaris eggs as a function of ammonia concentration and temperature. AB - Ammonia sanitization is a promising technology for sanitizing human excreta intended for use as a fertilizer in agriculture. Ascaris eggs are the most persistent pathogens regarding ammonia inactivation and are commonly present in fecal sludge in low- and middle-income countries. In this study, a model for predicting ammonia inactivation of ascaris eggs was developed. Data from four previous studies were compiled and analyzed statistically, and a mathematical model for the treatment time required for inactivation was created. The inactivation rate increased with NH3 activity to the power of 0.7. The required treatment time was found to decrease 10-fold for each 16 degrees C temperature increase. Dry matter (DM) content and pH had no direct effect on inactivation, but had an indirect effect due to their impact on NH3 activity, which was estimated using the Pitzer approach. An additional model giving an approximation of Pitzer NH3 activity but based on the Emerson approach, DM content and total ammonia (NHTot) was also developed. The treatment time required for different log10 reductions of ascaris egg viability can thus easily be estimated by the model as a function of NH3 activity and temperature. The impact on treatment time by different treatment options can then be theoretically evaluated, promoting improvements of the treatment e.g. by adding urea or alkaline agents, or increasing the temperature by solar heating. PMID- 26143273 TI - Modeling the low pH limit of Nitrosomonas eutropha in high-strength nitrogen wastewaters. AB - In wastewater treatment, the rate of ammonia oxidation decreases with pH and stops very often slightly below a pH of 6. Free ammonia (NH3) limitation, inhibition by nitrous acid (HNO2), limitation by inorganic carbon or direct effect of high proton concentrations have been proposed to cause the rate decrease with pH as well as the cessation of ammonia oxidation. In this study, we compare an exponential pH term common for food microbiology with conventionally applied rate laws based on Monod-type kinetics for NH3 limitation and non competitive HNO2 inhibition as well as sigmoidal pH functions to model the low pH limit of ammonia oxidizing bacteria (AOB). For this purpose we conducted well controlled batch experiments which were then simulated with a computer model. The results showed that kinetics based on NH3 limitation and HNO2 inhibition can explain the rate decrease of ammonia oxidation between pH 7 and 6, but fail in predicting the pH limit of Nitrosomonas eutropha at pH 5.4 and rates close to that limit. This is where the exponential pH term becomes important: this term decreases the rate of ammonia oxidation to zero, as the pH limit approaches. Previously proposed sigmoidal pH functions that affect large pH regions, however, led to an overestimation of the pH effect and could therefore not be applied successfully. We show that the proposed exponential pH term can be explained quantitatively with thermodynamic principles: at low pH values, the energy available from the proton motive force is too small for the NADH production in Nitrosomonas eutropha and related AOB causing an energy limited state of the bacterial cell. Hence, energy limitation and not inhibition or limitation of enzymes is responsible for the cessation of the AOB activity at low pH values. PMID- 26143274 TI - Fate of geosmin and 2-methylisoborneol in full-scale water treatment plants. AB - The increasing frequency and intensity of taste and odour (T&O) producing cyanobacteria in water sources is a growing global issue. Geosmin and 2 methylisoborneol (MIB) are the main cyanobacterial T&O compounds and can cause complaints from consumers at levels as low as 10 ng/L. However, literature concerning the performance of full-scale treatment processes for geosmin and MIB removal is rare. Hence, the objectives of this study were to: 1) estimate the accumulation and breakthrough of geosmin and MIB inside full-scale water treatment plants; 2) verify the potential impact of sludge recycling practice on performance of plants; and, 3) assess the effectiveness of aged GAC for the removal of these compounds. Sampling after full-scale treatment processes and GAC pilot assays were conducted to achieve these goals. Geosmin and MIB monitoring in full-scale plants provided the opportunity to rank the performance of studied treatment processes with filtration and granular activated carbon providing the best barriers for removal of total and extracellular compounds, correspondingly. Geosmin was removed to a greater extent than MIB using GAC. Geosmin and MIB residuals in water post GAC contactors after two years of operation was 20% and 40% of initial concentrations, correspondingly. Biological activity on the GAC surface enhanced the removal of T&O compounds. These observations demonstrated that a multi-barrier treatment approach is required to ensure cyanobacteria and their T&O compounds are effectively removed from drinking water. PMID- 26143275 TI - The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer. AB - BACKGROUND: Silibinin has been known for its role in anti-cancer and radio protective effect. Radiation therapy for treating lung cancer might lead to late phase pulmonary inflammation and fibrosis. Thus, this study aimed to investigate the effects of silibinin in radiation-induced lung injury with a mouse model. METHODS: In this study, we examined the ability of silibinin to mitigate lung injury in, and improve survival of, C57BL/6 mice given 13 Gy thoracic irradiation and silibinin treatments orally at 100 mg/kg/day for seven days after irradiation. In addition, Lewis lung cancer (LLC) cells were injected intravenously in C57BL/6 mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with lung radiation therapy at 13 Gy and with silibinin at a dose of 100 mg/day for seven days after irradiation. RESULTS: Silibinin was shown to increase mouse survival, to ameliorate radiation-induced hemorrhage, inflammation and fibrosis in lung tissue, to reduce the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and to reduce inflammatory cell infiltration in the respiratory tract. In LLC tumor injected mice, lung tissue from mice treated with both radiation and silibinin showed no differences compared to lung tissue from mice treated with radiation alone. CONCLUSIONS: Silibinin treatment mitigated the radiation-induced lung injury possibly by reducing inflammation and fibrosis, which might be related with the improved survival rate. Silibinin might be a useful agent for lung cancer patients as a non-toxic complementary approach to alleviate the side effects by thorax irradiation. PMID- 26143276 TI - Using individualized opening pressure to determine the optimal setting of an adjustable proGAV shunt in treatment of hydrocephalus in infants. AB - INTRODUCTION: The aim of the study was to describe the authors' experiences with the adjustable gravitational proGAV shunt system in treating infants' hydrocephalus. PATIENTS AND METHODS: The proGAV was implanted in 29 infants (11 boys and 18 girls, median age 9 months) with hydrocephalus of various origins between January 2010 and June 2014. The opening pressure was chosen based on the intraventricular pressure which was measured during operation, and a gravitational unit with a fixed opening pressure (15 cm H2O) was selected. RESULT: Regular clinical follow up ranged from 6 to 36 months, with a mean follow up time of 15.7 +/- 7.9 months. Five of these patients (17.2%) underwent shunt revision because of malfunction, including two infections (6.9%), two shunt exposed (6.9%), and one proximal catheter occlusion (3.4%). For readjustment in 10 infants, the opening pressure was changed at least once during the follow-up period. CONCLUSION: The proGAV is efficacious in the treatment of hydrocephalus in infants. This individual selection of the opening pressures makes it probable that a better match of chosen opening pressure and actual hydraulic requirements of the patient might occur. PMID- 26143277 TI - Postoperative posterior fossa syndrome: unraveling the etiology and underlying pathophysiology by using magnetic resonance imaging. AB - BACKGROUND: Posterior fossa syndrome (PFS) is a severe, postoperative complication occurring in about 25 % of pediatric patients undergoing surgery for midline tumors in the posterior fossa. In recent years, MRI-based research elucidated the cause of PFS and shed new light on its putative pathophysiology. This review highlights the major advances arising from research of this topic. RESULTS: Postsurgical damage patterns in patients after posterior fossa surgery show that PFS results from bilateral surgical damage to the proximal efferent cerebellar pathways (pECPs). Surgical pECP disruption has other MRI-detectable effects that are more remote. Patients with PFS tend to develop global supratentorial cortical hypoperfusion, likely representing reversed, cerebello cerebral diaschisis. Because this hypoperfusion is most prominent in frontal regions, cerebellar mutism may indicate a dominantly frontal lobe dysfunction, hence a peculiar form of speech apraxia. Injury to the pECP also leads to contralateral inferior olivary nucleus degeneration. When bilateral hypertrophic olivary degeneration (HOD) is observed after posterior fossa surgery, affected patients have clinical PFS. Therefore, it is suggested that bilateral HOD may be a sensitive and, in appropriate clinical settings, reliable a posteriori surrogate imaging indicator of bilateral disruption of the pECPs and consequently of PFS. Having such a "validation tool" presents new opportunities to develop better definitions for the phenotypes within the clinical spectrum of PFS. CONCLUSIONS: Anatomical and functional MRI techniques are suitable and valuable tools with which to detect structural changes and pathophysiological processes in the development and evolution of PFS and may be key, integral components of future clinical research endeavors. PMID- 26143278 TI - Antioxidative enzymes in irradiated rat brain-indicators of different regional radiosensitivity. AB - PURPOSE: Previously, we examined manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and catalase (CAT) activities in rat brain irradiated with 2 or 3 Gy of gamma-rays. The results indicated that lower MnSOD activity and inducibility found in hippocampus might explain higher radiosensitivity of this brain region. Thus, in this study, we wanted to determine changes of MnSOD, CuZnSOD, and CAT activities after dose of 5 Gy and to find out if differences in MnSOD activity are caused by changes in its expression. METHODS: Heads of 4-day-old female rats were irradiated with gamma rays, using (60)Co. Animals were sacrificed 1/24 h after exposure. Hippocampus and cortex tissues were prepared for enzyme activity measurements and Western blot analysis. RESULTS: One hour after exposure, gamma-rays significantly decreased MnSOD activity in both examined brain regions. Twenty-four hours later, MnSOD recovery showed dose and regional dependence. It was weaker at higher doses and in hippocampal region. MnSOD expression changed in the similar manner as MnSOD activity only at lower doses of gamma-rays. In both examined brain regions, gamma radiation significantly decreased CuZnSOD activity and did not change activity of CAT. CONCLUSIONS: Our results confirmed that MnSOD plays an important role in different regional radiosensitivity but also showed that depending on dose, radiation affects MnSOD level by utterly different mechanisms. Postradiation changes of CuZnSOD and CAT are not regionally specific and therefore, cannot account for the different radiosensitivity of the hippocampus and cortex. PMID- 26143279 TI - Decompressive craniectomy for infants: a case series of five patients. AB - PURPOSE: Management of cerebral edema in infants is challenging. Decompressive craniectomy in young age has shown favorable outcomes for management of intracranial hypertension, but current literature is scarce and consists of only case reports or small series. The purpose of the current study is to report the challenges faced with this procedure and its complications in this peculiar age group. METHODS: This is a retrospective chart review of infants (less than 1 year of age) undergoing unilateral or bilateral decompressive craniotomy at a tertiary care hospital in Pakistan. Kochi score was used to score outcomes of five infants who underwent the procedure. RESULTS: Five infants were included in this series. Operative time for decompressive craniectomy (DC) ranged from 1 h and 40 min to 4 h. Three infants survived to undergo cranioplasty. Two infants recovered with good Kochi scores of 5a and one infant developed hemiparesis (Kochi score 3b). CONCLUSIONS: Decompressive craniectomy carries good outcomes in selected patients. Risk of bleeding and hemodynamic instability makes this procedure challenging. We found coagulopathy in four of the five patients which poses another challenge to the surgical management of these patients and has not been stressed enough in the previous literature. PMID- 26143280 TI - Reaction norm model to describe environmental sensitivity across first lactation in dairy cattle under tropical conditions. AB - Reaction norm models have been widely used to study genotype by environment interaction (G * E) in animal breeding. The objective of this study was to describe environmental sensitivity across first lactation in Brazilian Holstein cows using a reaction norm approach. A total of 50,168 individual monthly test day (TD) milk yields (10 test days) from 7476 complete first lactations of Holstein cattle were analyzed. The statistical models for all traits (10 TDs and for 305-day milk yield) included the fixed effects of contemporary group, age of cow (linear and quadratic effects), and days in milk (linear effect), except for 305-day milk yield. A hierarchical reaction norm model (HRNM) based on the unknown covariate was used. The present study showed the presence of G * E in milk yield across first lactation of Holstein cows. The variation in the heritability estimates implies differences in the response to selection depending on the environment where the animals of this population are evaluated. In the average environment, the heritabilities for all traits were rather similar, in range from 0.02 to 0.63. The scaling effect of G * E predominated throughout most of lactation. Particularly during the first 2 months of lactation, G * E caused reranking of breeding values. It is therefore important to include the environmental sensitivity of animals according to the phase of lactation in the genetic evaluations of Holstein cattle in tropical environments. PMID- 26143281 TI - Attenuated self-tickle sensation even under trajectory perturbation. AB - The efference copy account of the tickle effect (i.e., our inability to tickle ourselves) predicts no tickle effect (i.e., an ability to tickle ourselves) when the trajectory of a tactile stimulus is perturbed relative to the associated movement, and there is evidence in support of this. The active inference account, however, predicts the tickle effect should survive trajectory perturbation. We test these accounts of the tickle effect under the hypothesis that previous findings are due to attentional modulation, and that the tickle effect will be found in a paradigm with no conscious attention directed to the trajectory perturbation. We thus expected to find support for active inference. Our first experiment confirms this hypothesis, while our second seeks to explain previous findings in terms of the modulation of the tickle sensation when there is awareness of, and different degrees of attention to, the spatial tactile and kinesthetic trajectories. PMID- 26143282 TI - Prognostic value of variables derived from the six-minute walk test in patients with COPD: Results from the ECLIPSE study. AB - In addition to the six-min walk distance (6 MWD), other six-min walk test (6 MWT) derived variables, such as mean walk-speed (6MWSpeed), 6-min walk-work (6 MWW), distance-saturation product (DSP), exercise-induced oxygen desaturation (EID), and unintended stops may be useful for the prediction of mortality and hospitalization in patients with chronic obstructive pulmonary disease (COPD). We studied the association between 6 MWT-derived variables and mortality as well as hospitalization in COPD patients and compared it with the BODE index. A three year prospective study (ECLIPSE) to evaluate the prognostic value of 6 MWT derived variables in 2010 COPD patients. Cox's proportional-hazard regressions were performed to estimate 3-year mortality and hospitalization. During the follow-up, 193 subjects died and 622 were hospitalized. An adjusted Cox's regression model of hazard ratio [HR] for impaired 6 MWT-derived variables was significant referring to: mortality (6 MWD <=334 m [2.30], 6MWSpeed <=0.9 m/sec [2.15], 6 MWW <=20000 m kg [2.17], DSP <=290 m% [2.70], EID <=88% [1.75], unintended stops [1.99]; and hospitalization (6 MWW <=27000 m kg [1.23], EID <=88% [1.25], BODE index >=3 points [1.40]; all p <= 0.05). The 6 MWT-derived variables have an additional predictive value of mortality in patients with COPD. The 6 MWW, EID and the BODE index refine the prognosis of hospitalization. PMID- 26143283 TI - Evaluation of long-term outcomes of very old patients admitted to intensive care: Survival, functional status, quality of life, and quality-adjusted life-years. AB - PURPOSE: To evaluate long-term outcomes among a population of very old patients (>=80years) after nonelective intensive care unit (ICU) admission. METHODS: A retrospective study of very old patients admitted to a mixed ICU between 2006 and 2012 was conducted. A detailed description was made; functional status was assessed through the modified Rankin Scale and quality of life through EQ-5D-3L. Follow-up results are compared between 3 groups: very old with "old" (66-79 years) and "non-old" (<=65years) patients. RESULTS: A total of 278 very old patients were admitted into the ICU representing 10.3% of admissions. The mean (SD) Simplified Acute Physiology Score II was 61 (16) predicting a hospital mortality of 70%, and the observed hospital mortality was 53%. Two-year survival rate was 38%. Of the 158 patients who survived in the ICU, 51 were evaluated in the outpatient clinic, and of those, 25 (51%) had already resumed previous functional activity. Evaluation through the modified Rankin Scale showed that 29 (60%) remained independent in their daily activities. When comparing the 3 groups, several differences were observed between theme, with the oldest groups (>80years) reporting more problems in motility, self-care, and usual activities. The respondent's self-rated health through the median visual analog scale score on the day of the outpatient clinic appointment decreased with age. CONCLUSIONS: For those who survive, return to previous functional activity was likely. Long term survival and quality of life achieved afterward were translated in more than a year of perfect health status gained. PMID- 26143284 TI - The impact of age at diagnosis on socioeconomic inequalities in adult cancer survival in England. AB - BACKGROUND: Understanding the age at which persistent socioeconomic inequalities in cancer survival become apparent may help motivate and support targeting of cancer site-specific interventions, and tailoring guidelines to patients at higher risk. PATIENTS AND METHODS: We analysed data on more than 40,000 patients diagnosed in England with one of three common cancers in men and women, breast, colon and lung, 2001-2005 with follow-up to the end of 2011. We estimated net survival for each of the five deprivation categories (affluent, 2, 3, 4, deprived), cancer site, sex and age group (15-44, 45-54, 55-64, and 65-74 and 75 99 years). RESULTS: The magnitude and pattern of the age specific socioeconomic inequalities in survival was different for breast, colon and lung. For breast cancer the deprivation gap in 1-year survival widened with increasing age at diagnosis, whereas the opposite was true for lung cancer, with colon cancer having an intermediate pattern. The 'deprivation gap' in 1-year breast cancer survival widened steadily from -0.8% for women diagnosed at 15-44 years to -4.8% for women diagnosed at 75-99 years, and was the widest for women diagnosed at 65 74 years for 5- and 10-year survival. For colon cancer in men, the gap was widest in patients diagnosed aged 55-64 for 1-, 5- and 10-year survival. For lung cancer, the 'deprivation gap' in survival in patients diagnoses aged 15-44 years was more than 10% for 1-year survival in men and for 1- and 5-year survival in women. CONCLUSION: Our findings suggest that reduction of socioeconomic inequalities in survival will require updating of current guidelines to ensure the availability of optimal treatment and appropriate management of lung cancer patients in all age groups and older patients in deprived groups with breast or colon cancer. PMID- 26143285 TI - Neuroanatomical localization of nitric oxide synthase (nNOS) in the central nervous system of carp, Labeo rohita during post-embryonic development. AB - Nitric oxide (NO) is a chemically diffusible molecular messenger playing various roles in both vertebrates and invertebrates. Nitric oxide synthase (NOS) is the key enzyme in synthesis of NO. The neuroanatomical distribution pattern of neuronal nitric oxide synthase (nNOS) was studied and developing stages of Labeo rohita such as hatchlings (10-15mm), frys (15-35mm), semi-fingerlings (35-65mm), fingerlings (65-100mm) and adults (350-370mm) were used. In the telencephalon, nitrergic cells were observed in both pallial and subpallial regions along with entopeduncular nucleus suggesting the involvement of NO in the control of sensory functions throughout the development. In the diencephalon, nNOS positive neurons were localized in the nucleus preopticus periventricularis and preopticus parvocellularis throughout development while nucleus preopticus magnocellularis was found immunopositive only in adult specimens who suggest the involvement of NO in the hormonal regulation. nNOS immunoreaction was also noted in suprachaismatic nucleus, habenula, lateral tuberal nucleus, paraventricular organ and anterior division of preglomerular nucleus throughout development. In the mesencephalic region, nNOS immunoreactivity was seen in the optic tectum, torus longitudinalis, nucleus of median longitudinal fascicle and occulomotor nucleus indicate the role of NO in integration of visual inputs and modulates motor control of the eyes and movements. Caudally, in the rhombencephalon, the cerebellum, the nucleus reticularis, the octaval nucleus and the motor nucleus of vagal nerve were nNOS positive during development. nNOS reactive cells and fibers were noted in the spinal motor column, thus suggesting a role of NO in gestation and startle response from early development. PMID- 26143286 TI - MRI phenotypes of localized intravascular coagulopathy in venous malformations. AB - BACKGROUND: The incidence of localized intravascular coagulopathy (LIC) in venous malformations varies with lesion size and location, as well as the presence of palpable phleboliths. The development of LIC can cause pain and hemorrhage and can progress to disseminated intravascular coagulopathy (DIC) and thromboembolic disease resulting in death in some cases. Early recognition of LIC can relieve symptoms and prevent progression to life-threatening complications. OBJECTIVE: The aim of this work was to identify MRI features of venous malformation associated with LIC. We hypothesized that venous malformations with larger capacitance, slower flow and less physiological compression (greater stasis) were more likely to be associated with LIC. MATERIALS AND METHODS: In this HIPAA compliant and IRB-approved study, we retrospectively reviewed clinical records and MRI for consecutive patients undergoing evaluation of venous malformations at our multidisciplinary Birthmarks and Vascular Anomalies Center between 2003 and 2013. Inclusion required consensus diagnosis of venous malformation and availability of laboratory data and MRI; patients on anticoagulation or those previously undergoing surgical or endovascular treatment were excluded. LIC was diagnosed when D-dimer exceeded 1,000 ng/mL and/or fibrinogen was less than 200 mg/dL. Two board-certified radiologists assessed the following MRI features for each lesion: morphology (spongiform vs. phlebectatic), presence of phleboliths, size, location (truncal vs. extremity), and tissue type(s) involved (subcutis, muscle, bone and viscera). Univariate logistic regression analyses were used to test associations between LIC and MRI findings, and stepwise regression was applied to assess the significance of the individual imaging predictors. RESULTS: Seventy patients, 37 with LIC, met inclusion criteria during the 10-year study period (age: 14.5 +/- 13.6 years [mean +/- standard deviation]; 30 male, 40 female). Both elevated D-dimer and low fibrinogen were associated with the presence of phleboliths, larger lesion sizes and visceral involvement on MRI (all P < 0.05). In stepwise regressions, lesion size (P < 0.001), the presence of phleboliths (P = 0.005) and lesion morphology (P = 0.006) were all significant predictors of LIC. CONCLUSION: LIC is associated with larger lesion size, visualized phleboliths, truncal location and spongiform morphology on MRI in venous malformations, suggesting that lesions with larger capacitance, slower flow and less physiological compression are more likely to be associated with coagulopathy. PMID- 26143287 TI - Pycnodysostosis with a patella fracture. PMID- 26143288 TI - Added value of experts' knowledge to improve a quantitative microbial exposure assessment model--Application to aseptic-UHT food products. AB - In a previous study, a quantitative microbial exposure assessment (QMEA) model applied to an aseptic-UHT food process was developed [Pujol, L., Albert, I., Magras, C., Johnson, N. B., Membre, J. M. Probabilistic exposure assessment model to estimate aseptic UHT product failure rate. 2015 International Journal of Food Microbiology. 192, 124-141]. It quantified Sterility Failure Rate (SFR) associated with Bacillus cereus and Geobacillus stearothermophilus per process module (nine modules in total from raw material reception to end-product storage). Previously, the probabilistic model inputs were set by experts (using knowledge and in-house data). However, only the variability dimension was taken into account. The model was then improved using expert elicitation knowledge in two ways. First, the model was refined by adding the uncertainty dimension to the probabilistic inputs, enabling to set a second order Monte Carlo analysis. The eight following inputs, and their impact on SFR, are presented in detail in this present study: D-value for each bacteria of interest (B. cereus and G. stearothermophilus) associated with the inactivation model for the UHT treatment step, i.e., two inputs; log reduction (decimal reduction) number associated with the inactivation model for the packaging sterilization step for each bacterium and each part of the packaging (product container and sealing component), i.e., four inputs; and bacterial spore air load of the aseptic tank and the filler cabinet rooms, i.e., two inputs. Second, the model was improved by leveraging expert knowledge to develop further the existing model. The proportion of bacteria in the product which settled on surface of pipes (between the UHT treatment and the aseptic tank on one hand, and between the aseptic tank and the filler cabinet on the other hand) leading to a possible biofilm formation for each bacterium, was better characterized. It was modeled as a function of the hygienic design level of the aseptic-UHT line: the experts provided the model structure and most of the model parameters values. Mean of SFR was estimated to 10*10(-8) (95% Confidence Interval=[0*10(-8); 350*10(-8)]) and 570*10(-8) (95% CI=[380*10(-8); 820*10(-8)]) for B. cereus and G. stearothermophilus, respectively. These estimations were more accurate (since the confidence interval was provided) than those given by the model with only variability (for which the estimates were 15*10(-8) and 580*10(-8) for B. cereus and G. stearothermophilus, respectively). The updated model outputs were also compared with those obtained when inputs were described by a generic distribution, without specific information related to the case-study. Results showed that using a generic distribution can lead to unrealistic estimations (e.g., 3,181,000 product units contaminated by G. stearothermophilus among 10(8) product units produced) and emphasized the added value of eliciting information from experts from the relevant specialist field knowledge. PMID- 26143289 TI - Characterization of specific alleles in InlA and PrfA of Listeria monocytogenes isolated from foods in Osaka, Japan and their ability to invade Caco-2 cells. AB - Listeria monocytogenes expresses the surface protein internalin A (InlA), enabling the invasion of human intestinal epithelial cells to cause severe food borne diseases. Full-length sequence analysis of inlA of 114 food isolates resulted in the detection of 29 isolates with a premature stop codon (PMSC) mutation and 6 isolates with 3-codon deletion mutations (aa 738 to 740) in inlA. The isolates with inlA PMSCs demonstrated a significantly lower level of invasion than the other food isolates in a Caco-2 cell invasion assay (P<0.01), but the isolates with the 3-codon deletion exhibited invasion comparable to the isolates with non-truncated InlA (P>0.05). According to analysis of the positive regulatory factor A (PrfA) sequences of 114 L. monocytogenes isolates, 7 isolates of serotype 1/2a from chicken samples contained a PrfA protein with a 5 nucleotide deletion from 712 to 716, including a stop codon. Although the isolates with a 5-nucleotide deletion in prfA demonstrated invasion comparable to the isolates with non-truncated InlA and PrfA after growth at 30 degrees C (P>0.05), they exhibited a significantly higher level of invasion than the other isolates after growth at 20 degrees C (P<0.01). To the authors' knowledge, this is the first report of L. monocytogenes isolates with the stop-codon deletion of PrfA. PMID- 26143290 TI - Pediatric open-globe injuries: clinical characteristics and factors associated with poor visual and anatomical success. AB - PURPOSE: We determine the clinical characteristics, visual and anatomical outcomes, and factors associated with poor visual outcome and anatomical success in pediatric open-globe injuries (OGI). METHODS: The records of patients aged 17 years and younger who had undergone surgical intervention after OGI between January 2000 and June 2010 were reviewed retrospectively. RESULTS: In total, 182 patients were enrolled in the study (70.9 % males, 29.1 % females; mean age: 8.6 +/- 4.5 years [range 1-17 years]). Injuries occurred mostly at home (45.1 %). Objects most often causing the ocular trauma were sharp objects (74.1 %). Over one-third of the eyes (39.7 %) had final visual acuities of 20/200 or better. Anatomical success was achieved in 76.9 % of eyes. Time between primary globe repair and secondary surgical intervention was 61.4 +/- 144 days. Visual outcomes were poor in eyes with initial visual acuity less than for counting fingers, retinal detachment, proliferative vitreoretinopathy, and endophthalmitis. Anatomical success rates were low with retinal detachment. CONCLUSION: Visual outcomes seem to be poor in more than half of the patients despite advanced microsurgical techniques. PMID- 26143291 TI - Inhibition of p38 mitogen-activated protein kinase phosphorylation decreases H2O2 induced apoptosis in human lens epithelial cells. AB - BACKGROUND: Oxidative damage resulting from ROS is a known causal factor for cataractogenesis. The mitogen-activated protein kinases (MAPK) pathway plays an important role in the apoptosis of HLE cells. The purpose of this study was to investigate the role of phosphorylated p38 mitogen-activated protein kinase in H2O2-induced apoptosis in cultured human lens epithelial (HLE) cells. METHODS: The effect of SB203580 on HLE cells treated with H2O2 was determined by various assays. Cell viability was monitored by the MTT assay. The rates of apoptosis and ROS generation were determined by flow cytometric analysis. The numbers of mitotic and apoptotic cell nuclei were determined after staining with Hoechst 33342. The protein level of phospho-p38 was measured using western blot analysis. RESULTS: SB203580 reduced H2O2-induced cellular apoptosis and inhibited the generation of reactive oxygen species (ROS); it also delayed the progression of H2O2-induced opacification of lenses. The level of p-p38 was increased when cells were exposed to H2O2 and significantly SB203580-inhibited phosphorylation of p38. The p38MAPK pathway plays an important role in H2O2-induced apoptosis of HLE cells. CONCLUSIONS: The study demonstrates that activation of p38MAPK plays an important role in H2O2-induced apoptosis of HLE cells. SB203580 may potentially be exploited as a useful tool for cataract prevention. PMID- 26143292 TI - Phylogeny of frogs from the genus Physalaemus (Anura, Leptodactylidae) inferred from mitochondrial and nuclear gene sequences. AB - Although some species groups have been recognized in the leiuperine genus Physalaemus, no phylogenetic analysis has previously been performed. Here, we provide a phylogenetic study based on mitochondrial and nuclear DNA sequences from 41 of the 46 species of Physalaemus. We employed the parsimony criterion using the software TNT and POY and the Bayesian criterion using the software MrBayes. Two major clades were recovered inside the monophyletic Physalaemus: (i) the highly supported Physalaemus signifer Clade, which included P. nattereri and the species previously placed in the P. deimaticus and P. signifer Groups; and (ii) the Physalaemus cuvieri Clade, which included the remaining species of Physalaemus. Five species groups were recognized in the P. cuvieri Clade: the P. biligonigerus Group, the P. cuvieri Group, the P. henselii Group, the P. gracilis Group and the P. olfersii Group. The P. gracilis Species Group was the same as that previously proposed by Nascimento et al. (2005). The P. henselii Group includes P. fernandezae and P. henselii, and was the sister group of a clade that comprised the remaining species of the P. cuvieri Clade. The P. olfersii Group included P. olfersii, P. soaresi, P. maximus, P. feioi and P. lateristriga. The P. biligonigerus Species Group was composed of P. biligonigerus, P. marmoratus, P. santafecinus and P. riograndensis. The P. cuvieri Group inferred here differed from that recognized by Nascimento et al. (2005) only by the inclusion of P. albifrons and the exclusion of P. cicada. The paraphyly of P. cuvieri with respect to P. ephippifer was inferred in all the analyses. Distinct genetic lineages were recognized among individuals currently identified as P. cuvieri and they were congruent with cytogenetic differences reported previously, supporting the hypothesis of occurrence of formally unnamed species. PMID- 26143293 TI - Participation in a Structured Weight Loss Program and All-Cause Mortality and Cardiovascular Morbidity in Obese Patients With Chronic Kidney Disease. AB - OBJECTIVE: To determine if participation in a weight loss program impacted upon a composite end point of all-cause mortality and cardiovascular morbidity in obese patients with chronic kidney disease (CKD). DESIGN: Retrospective cohort study. SUBJECTS: All patients with a body mass index (BMI) >30 kg/m(2) or >28 kg/m(2) with at least 1 comorbidity (hypertension, diabetes, or dyslipidemia) referred to an established weight management program (WMP) from 2005 to 2009 at a metropolitan tertiary teaching hospital were eligible for inclusion in the study cohort. INTERVENTION: Twelve-month structured weight loss program. MAIN OUTCOME MEASURES: Combined outcome of all-cause mortality, myocardial infarction, stroke, and hospitalization for congestive heart failure; kidney transplantation waitlisting. RESULTS: A total of 169 obese patients with CKD commenced the WMP and 169 did not-becoming the observational control group (CON). There were no significant differences between groups for age, BMI, sex, ethnicity, smoking, hypertension, or kidney function at baseline, although CON included more patients with diabetes than WMP (49% vs. 38%, P = .03). Kaplan-Meier survival analysis with log-rank test differed between groups for the combined outcome (P = .03). Cox regression analysis with adjustment for age, sex, ethnicity, hypertension, diabetes, kidney function, baseline BMI, and smoking status, indicated that patients in WMP had a significantly longer event-free period for the combined outcome, than those in CON (adjusted hazard ratio 0.53; 95% confidence interval [CI] 0.29-0.97; P = .04). Participation in the WMP did not increase the likelihood of kidney transplantation waitlisting (odds ratio [OR] 1.06; 95% CI 0.39-2.87; P = .9). Lower baseline BMI and greater weight loss over 12 months were the only factors related to kidney transplantation waitlisting (adjusted R(2) = 0.426). CONCLUSIONS: Participation in a structured weight loss program may be associated with improved outcomes in obese patients with CKD. PMID- 26143294 TI - Non-aneurysmal aberrant right subclavian artery causing dysphagia in a young girl: challenges encountered using supraclavicular approach. AB - Aberrant right subclavian artery is the most common anomaly of the aortic arch. Patients are often asymptomatic and discovered accidentally. Occasionally, they present with symptoms related to oesophageal or tracheal compression.A 13-year old girl presented with dysphagia and stridor was found to have an aberrant right subclavian artery. Surgical division and reconstruction of the artery was performed initially through right supraclavicular approach. An additional left thoracotomy was performed to overcome the challenges encountered at initial operation. PMID- 26143295 TI - Masseteric-facial nerve transposition for reanimation of the smile in incomplete facial paralysis. AB - Incomplete facial paralysis occurs in about a third of patients with Bell's palsy. Although their faces are symmetrical at rest, when they smile they have varying degrees of disfigurement. Currently, cross-face nerve grafting is one of the most useful techniques for reanimation. Transfer of the masseteric nerve, although widely used for complete paralysis, has not to our knowledge been reported for incomplete palsy. Between December 2008 and November 2013, we reanimated the faces of 9 patients (2 men and 7 women) with incomplete unilateral facial paralysis with transposition of the masseteric nerve. Sex, age at operation, cause of paralysis, duration of denervation, recipient nerves used, and duration of follow-up were recorded. Commissural excursion, velocity, and patients' satisfaction were evaluated with the FACIAL CLIMA and a questionnaire, respectively. The mean (SD) age at operation was 39 (+/-6) years and the duration of denervation was 29 (+/-19) months. There were no complications that required further intervention. Duration of follow-up ranged from 6-26 months. FACIAL CLIMA showed improvement in both commissural excursion and velocity of more than two thirds in 6 patients, more than one half in 2 patients and less than one half in one. Qualitative evaluation showed a slight or pronounced improvement in 7/9 patients. The masseteric nerve is a reliable alternative for reanimation of the smile in patients with incomplete facial paralysis. Its main advantages include its consistent anatomy, a one-stage operation, and low morbidity at the donor site. PMID- 26143296 TI - Definitive surgical management of staple line leak after sleeve gastrectomy. AB - BACKGROUND: Sleeve gastrectomy (SG) has become a widely adopted bariatric surgical procedure. The most serious complication is staple line leak (SLL), which is potentially life threatening and, in some patients, becomes chronic and difficult to manage. Definitive surgical management of SLL is effective but seldom published in the literature. OBJECTIVES: This study aims to review the outcome of definitive surgical management of SLL after SG, looking at short-term and long-term results. SETTING: Single surgeon experience based at a tertiary university hospital in Beirut, Lebanon. METHODS: Retrospective review of records of patients with SLL who underwent definitive surgical treatment by the senior author (B.Y.S.) from January 2008 until December 2013. RESULTS: Ten patients (50% female) underwent definitive surgical repair during the study period. The mean age, weight, and body mass index at the time of SG were 35 years, 121 kg, and 41.5 kg/m(2), respectively. Most leaks (90%) were at the esophagogastric junction. All underwent multiple operative, endoscopic, or radiologic procedures before definitive surgical repair. Methods of definitive repair included open Roux-en-Y (RY) esophagojejunostomy (70%), open RY gastric bypass (10%), laparoscopic RY esophagojejunostomy (10%), and one laparoscopic RY fistulojejunostomy (10%). Six patients (60%) underwent definitive surgical treatment because of chronic SLL, on average, 26 weeks after leak detection (range 13-39 wk). The other 4 underwent repair earlier, on average 4 weeks after leak detection (1-7 wk). There were no mortalities, and all patients healed without residual leak. Perioperative morbidity developed in 1 of 6 (17%) patients who underwent delayed repair and in 75% of patients who underwent repair early. Patients who underwent early repair were heavier (body mass index 40.5 kg/m(2) versus 30 kg/m(2)) and nutritionally more deplete (albumin 26.7 g/L versus 39.2 g/L). All patients are well at a mean follow-up of 21.6 months (7.5-55.9 mo) with an average percentage excess weight loss of 74% (57%-120%). CONCLUSIONS: Definitive surgical management of SLL was uniformly effective with acceptable morbidity. It is indicated in patients with chronic persistent fistula beyond 12 weeks, provided patients are kept in good nutritional state. Some select patients may benefit from this approach in the early phases, but the surgical risks are higher. PMID- 26143297 TI - Mucosal glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide cell numbers in the super-obese human foregut after gastric bypass. AB - BACKGROUND: Super-obesity, a body mass index>50 kg/m(2), is difficult to treat. Many studies have focused on the anatomic changes of the intestines; the physiologic background is not clearly identified. It is established that Roux-en Y gastric bypass (RYGB) augments secretion of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and insulin, but other aspects of gut hormone cell function in the alimentary limb are unknown. OBJECTIVE: To study the effects of laparoscopic RYGB on enteroendocrine cells. SETTING: University-affiliated, high-volume bariatric surgery center. METHODS: Eighteen nondiabetic patients were drawn from the present study (NCT 01514799), randomizing between biliopancreatic (BP) limbs of either 60 cm (BP60) or 200 cm (BP200). Demographic characteristics did not differ at baseline or 12 months. Pouch and jejunal biopsies were obtained intraoperatively and using endoscopy at 12 months. Mucosal height and density of hormone-producing cell populations were assessed and mRNA expression measured with real-time polymerase chain reaction. RESULTS: In perianastomotic jejunum, a 4.9-fold increase in GLP-1 cell density was evident 12 months after RYGB, most pronounced in the BP200-group. The densities of glucose-dependent insulinotropic polypeptide (GIP) cells and PYY immunoreactive cells were doubled after 12 months. GIP mRNA was unaffected, but GLP-1 and PYY mRNA were lower 12 months after RYGB. RYGB had no impact on villi length or density of ghrelin-, cholecystokinin-, neurotensin-, secretin-, or serotonin-producing cells after 12 months. Pouch mucosal height and cell densities of ghrelin-, histamine-, serotonin-, and somatostatin-producing cells remained unaffected by RYGB in both groups. CONCLUSIONS: RYGB selectively increased the density of incretin-producing cell populations in the jejunum. This may provide anatomic explanation for the observed increased plasma levels of incretins. PMID- 26143298 TI - The effects of crowding on eye movement patterns in reading. AB - Crowding is a phenomenon that characterizes normal periphery limiting letter identification when other letters surround the signal. We investigated the nature of the reading limitation of crowding by analyzing eye-movement patterns. The stimuli consisted of two items varying across trials for letter spacing (spaced, unspaced and increased size), lexicality (words or pseudowords), number of letters (4, 6, 8), and reading modality (oral and silent). In Experiments 1 and 2 (oral and silent reading, respectively) the results show that an increase in letter spacing induced an increase in the number of fixations and in gaze duration, but a reduction in the first fixation duration. More importantly, increasing letter size (Experiment 3) produced the same first fixation duration advantage as empty spacing, indicating that, as predicted by crowding, only center-to-center letter distance, and not spacing per se, matters. Moreover, when the letter size was enlarged the number of fixations did not increase as much as in the previous experiments, suggesting that this measure depends on visual acuity rather than on crowding. Finally, gaze duration, a measure of word recognition, did not change with the letter size enlargement. No qualitative differences were found between oral and silent reading experiments (1 and 2), indicating that the articulatory process did not influence the outcome. Finally, a facilitatory effect of lexicality was found in all conditions, indicating an interaction between perceptual and lexical processing. Overall, our results indicate that crowding influences normal word reading by means of an increase in first fixation duration, a measure of word encoding, which we interpret as a modulatory effect of attention on critical spacing. PMID- 26143299 TI - Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation. AB - BACKGROUND: The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. METHODS: Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored. RESULTS: Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. CONCLUSIONS: The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. PMID- 26143301 TI - Universal challenges for parasite control: a perspective from equine parasitology. AB - Formulating and disseminating recommendations for parasite control is a dynamic process that requires constant interaction between parasitology researchers and the end-users in the field. Any set of guidelines requires continuous evaluation of efficacy and possible adverse effects, and adjustments are invariably needed along the way. Experience with formulating guidelines for equine parasite control illustrates that end-users struggle with striking the balance between treating too little and too much. PMID- 26143300 TI - High uptake of naloxone-based overdose prevention training among previously incarcerated syringe-exchange program participants. AB - BACKGROUND: Incarceration is common among people who inject drugs. Prior research has shown that incarceration is a marker of elevated risk for opioid overdose, suggesting that the criminal justice system may be an important, under-utilized venue for implementing overdose prevention strategies. To better understand the feasibility and acceptability of such strategies, we evaluated the utilization of naloxone-based overdose prevention training among people who inject drugs with and without a history of incarceration. METHODS: We surveyed clients who utilize a multi-site syringe exchange program (SEP) in 2 cities in the Midwestern United States. Participants completed an 88-item, computerized survey assessing history of incarceration, consequences associated with injection, injecting practices, and uptake of harm reduction strategies. RESULTS: Among 543 respondents who injected drugs in the prior 30 days, 243 (43%) reported prior incarceration. Comparing those with and without a history of incarceration, there were no significant differences with respect to age, gender, or race. Those who observed an overdose, experienced overdose, and received training to administer or have administered naloxone were more likely to report incarceration. Overall, 69% of previously incarcerated clients had been trained to administer naloxone. CONCLUSION: People who inject drugs with a history of incarceration appear to have a higher risk of opioid overdose than those never incarcerated, and are more willing to utilize naloxone as an overdose prevention strategy. Naloxone training and distribution is an important component of comprehensive prevention services for persons with opioid use disorders. Expansion of services for persons leaving correctional facilities should be considered. PMID- 26143302 TI - Relationship of adiponectin and its multimers to metabolic indices in cats during weight change. AB - Adiponectin is an important anti-inflammatory hormone secreted from adipose tissue. The high-molecular-weight form of adiponectin (HMW) closely correlates with insulin sensitivity in human beings. This study uses a novel method of size exclusion gel chromatography combined with enzyme-linked immunosorbent assay to measure HMW feline adiponectin and determine its relationship to leptin, cholesterol, and insulin sensitivity as cats gain and lose weight. In addition, total adiponectin and its messenger RNA expression in subcutaneous adipose tissue were measured. No correlations were found between total serum adiponectin and subcutaneous adipose messenger RNA expression, fat mass, or measures of insulin sensitivity. This study demonstrates that cats have high percentages of HMW adiponectin. Although weak correlations between HMW adiponectin and fat mass were detected, additional cats are needed to determine if the correlations are significant. PMID- 26143303 TI - Twenty-four-hour profiles of metabolic and stress hormones in sheep selected for a calm or nervous temperament. AB - Even in the absence of stressors, temperament is associated with changes in the concentration of stress-responsive hormones and, possibly because of such changes, temperament can affect metabolism. We tested whether, in sheep bred for temperament for 14 generations, "nervous" females have greater concentrations of stress-responsive hormones in the absence of stressors than "calm" females, and whether these differences are associated with changes in the concentrations of metabolic hormones. In resting "calm" (n = 8) and "nervous" (n = 8) sheep, concentrations of cortisol, prolactin, leptin, and insulin were measured in blood plasma sampled via jugular catheter every 20 min for 24 h. The animals were individually penned, habituated to their housing and human handling over 7 wk, and fed before sampling began. Diurnal variation was evident for all hormones, but a 24-h cortisol pattern was detected in only 7 individuals. There was no effect of temperament on any aspect of concentrations of cortisol or prolactin, but "calm" animals had greater concentrations of insulin in the early afternoon than "nervous" animals (14.5 +/- 1.1 vs 10.0 +/- 1.6 MUU/mL; P = 0.038), and a similar tendency was seen for leptin (P = 0.092). We conclude that selection for temperament affects the concentration of metabolic hormones in the absence of stressors, but this effect is independent of stress-responsive hormones. PMID- 26143304 TI - Unusual reason of spinal cord infarction: tuberculous meningitis. PMID- 26143305 TI - Beyond the core face-processing network: Intracerebral stimulation of a face selective area in the right anterior fusiform gyrus elicits transient prosopagnosia. AB - According to neuropsychological evidence, a distributed network of regions of the ventral visual pathway - from the lateral occipital cortex to the temporal pole - supports face recognition. However, functional magnetic resonance imaging (fMRI) studies have generally confined ventral face-selective areas to the posterior section of the occipito-temporal cortex, i.e., the inferior occipital gyrus occipital face area (OFA) and the posterior and middle fusiform gyrus fusiform face area (FFA). There is recent evidence that intracranial electrical stimulation of these areas in the right hemisphere elicits face matching and recognition impairments (i.e., prosopagnosia) as well as perceptual face distortions. Here we report a case of transient inability to recognize faces following electrical stimulation of the right anterior fusiform gyrus, in a region located anteriorly to the FFA. There was no perceptual face distortion reported during stimulation. Although no fMRI face-selective responses were found in this region due to a severe signal drop-out as in previous studies, intracerebral face-selective event-related potentials and gamma range electrophysiological responses were found at the critical site of stimulation. These results point to a causal role in face recognition of the right anterior fusiform gyrus and more generally of face-selective areas located beyond the "core" face-processing network in the right ventral temporal cortex. It also illustrates the diagnostic value of intracerebral electrophysiological recordings and stimulation in understanding the neural basis of face recognition and visual recognition in general. PMID- 26143306 TI - Experimental approaches to phenotypic diversity in infection. AB - Microbial infections are burdening human health, even after the advent of antibiotics, vaccines and hygiene. Thus, infection biology has aimed at the molecular understanding of the pathogen-host interaction. This has revealed key virulence factors, host cell signaling pathways and immune responses. However, our understanding of the infection process is still incomplete. Recent evidence suggests that phenotypic diversity can have important consequences for the infection process. Diversity arises from the formation of distinct subpopulations of pathogen cells (with distinct virulence factor expression patterns) and host cells (with distinct response capacities). For technical reasons, such phenotypic diversity has often been overlooked. We are highlighting several striking examples and discuss the experimental approaches available for analyzing the different subpopulations. Single cell reporters and approaches from systems biology do hold much promise. PMID- 26143307 TI - The nano-epsilon dot method for strain rate viscoelastic characterisation of soft biomaterials by spherical nano-indentation. AB - Nano-indentation is widely used for probing the micromechanical properties of materials. Based on the indentation of surfaces using probes with a well-defined geometry, the elastic and viscoelastic constants of materials can be determined by relating indenter geometry and measured load and displacement to parameters which represent stress and deformation. Here we describe a method to derive the viscoelastic properties of soft hydrated materials at the micro-scale using constant strain rates and stress-free initial conditions. Using a new self consistent definition of indentation stress and strain and corresponding unique depth-independent expression for indentation strain rate, the epsilon dot method, which is suitable for bulk compression testing, is transformed to nano indentation. We demonstrate how two materials can be tested with a displacement controlled commercial nano-indentor using the nano-espilon dot method (nano epsilonM) to give values of instantaneous and equilibrium elastic moduli and time constants with high precision. As samples are tested in stress-free initial conditions, the nano-epsilonM could be useful for characterising the micro mechanical behaviour of soft materials such as hydrogels and biological tissues at cell length scales. PMID- 26143308 TI - Quantitative physical and handling characteristics of novel antibacterial braided silk suture materials. AB - Surgical braided silk sutures have been widely used because these materials exhibit good handling characteristics, ease of use, and ideal knot security. However, surgical silk sutures likely cause surgical site infections because these sutures are composed of natural protein materials with a braided structure. As such, antibacterial silk sutures for clinical wound closure should be developed. Braided silk suture could be treated and modified with antibacterial agent, provided that excellent physical and handling characteristics of this material should maximize maintained. This study aimed to quantitatively investigate the effect of antibacterial treatment with different parameters on physical and handling characteristics of novel antibacterial braided silk sutures. Physical and handling characteristics, including appearance, knot-pull tensile strength, pullout friction resistance, tissue drag friction resistance, and bending stiffness, were evaluated. After physical and handling tests were conducted, images showed morphological characteristics were obtained and evaluated to investigate the relationship between antibacterial treatment and physical and handling properties. Results showed that suture diameter increased and reached the nearest thick size specification; knot-pull tensile strength decreased but remained higher than the standard value by at least 40.73%. Fracture asynchronism during knot-pull tensile strength test suggested that the fineness ratio of shell and core strands may enhance knot-pull tensile strength. Static and dynamic frictions of suture-to-suture friction behavior were slightly affected by antibacterial treatment, and changed to less than 16.07% and 32.77%, respectively. Suture-to-tissue friction and bending stiffness increased by approximately 50%; the bending stiffness of the proposed suture remained efficient compared with that of synthetic sutures. Therefore, good physical and handling characteristics can be maintained by selecting appropriate coating parameters. PMID- 26143309 TI - Free-running EMG monitoring during microvascular decompression for hemifacial spasm. AB - BACKGROUND: The aim of this work is to determine if free-running electromyography (frEMG) can detect activity before and after microvascular decompression (MVD) treatment for hemifacial spasm (HFS), and to evaluate correlations of frEMG findings with abnormal muscle responses (AMRs) or facial motor-evoked potentials (FMEPs). METHODS: To elicit nerve responses while carrying out frEMG recording before and after MVD, saline, a lactic solution, or artificial cerebrospinal fluid was injected onto the root exit zone of the facial nerve. RESULTS: Significantly higher frEMG activity was observed following saline injection than for the other solutions (p < 0.01). For frEMG activity ratios of >= 50 %, there was a trend towards a greater likelihood of persistent AMRs. When frEMG activity decreased after MVD in the mentalis muscles, FMEP amplitude ratios were significantly smaller than when it did not (65 vs. 94 %, p < 0.05). CONCLUSIONS: Changes in intraoperative frEMG, AMRs, and FMEPs likely reflect a component of the normalization of hyper-excitability of the facial nerve by MVD for HFS. PMID- 26143310 TI - Pentax Airway Scope AWS-S200 video laryngoscope for child tracheal intubation in a manikin study with 3 airway scenarios. AB - BACKGROUND: Endotracheal intubation is considered a criterion standard for securing the airway during cardiopulmonary resuscitation, yet it requires a very skillful operator. The aim of the study was to investigate whether paramedic staff can successfully use the Pentax Airway Scope AWS-S200 video laryngoscope (AWS) for intubating with 3 simulated airway scenarios. METHODS: It was a randomized nonblinded crossover simulation trial. Fifty-four paramedics performed intubation using an AWS in a manikin, with 3 airway scenarios: scenario A, normal airway; scenario B, normal airway with chest compression (CC); and scenario C, difficult airway with CC. RESULTS: Median intubation times for the AWS during scenarios A, B, and C were 20 seconds (interquartile range [IQR], 19-23 seconds), 22 seconds (IQR, 20-25 seconds), and 26 seconds (IQR, 23-29 seconds), respectively, and the respective overall success rates of intubation were 100%, 100%, and 94.4%. CONCLUSION: In this manikin study, paramedics could successfully intubate using the AWS, regardless of CCs being interrupted or not, even when a patient's airway was difficult. PMID- 26143311 TI - Hyperthermia and severe rhabdomyolysis from synthetic cannabinoids. AB - Synthetic cannabinoids (SC) have exploded on to the scene. With this rise in SC use, the number of complications and potential adverse effects are also well documented in the literature and is on the rise. The most frequently cited side effects are behavioral in nature and range for severe agitation to psychosis and delirium. We report a case of hyperthermia with severe rhabdomyolysis from SC use. PMID- 26143312 TI - Atrial septal defect can mimic pulmonary thromboembolism after a major surgery. AB - Trauma-related embolic events in pulmonary vascular bed are generally due to fat or thrombus embolism. In this report, we present a patient who had severe hypoxia and tachycardia at postoperative period after surgery of an open tibia fracture. Because of the clinical and electrocardiographic findings, we calculated patients Wells score as "pulmonary embolism likely" (N4 points, 28%-52% pulmonary embolism risk), and we performed chest contrast computed tomography. There was no abnormal finding in contrast to chest contrast computed tomography that could suggest fat or thrombus embolism. Because of persistent hypoxemia, we performed transthoracic echocardiographic examination to exclude an intracardiac shunt. In transthoracic echocardiographic examination, we found an atrial septal defect with intermittent right-to-left shunt due to high central venous pressure. PMID- 26143313 TI - Efficacy and safety of nebulized morphine given at 2 different doses compared to IV titrated morphine in trauma pain. AB - BACKGROUND: Our aim was to compare the efficacy and safety of intravenous (IV) titrated morphine with nebulized morphine given at 2 different doses in severe traumatic pain. METHODS: In a prospective, randomized, controlled double-blind study, we included 300 patients with severe traumatic pain. They were assigned to 3 groups: Neb10 group received 1 nebulization of 10-mg morphine; Neb20 group received 1 nebulization of 20-mg morphine, repeated every 10 minutes with a maximum of 3 nebulizations; and the IV morphine group received 2-mg IV morphine repeated every 5 minutes until pain relief. Visual analog scale was monitored at baseline, 5, 10, 15, 20, 25, 30, and 60 minutes after the start of drug administration. Treatment success was defined by the percentage of patients in whom visual analog scale decreased greater than or equal to 50% of its baseline value. When this end point was not reached, rescue morphine was administered. Pain resolution time was defined by the elapsed time between the start of the protocol and the reach of treatment success criteria. RESULTS: Success rate was significantly better at 97% (95% confidence interval [CI], 93-100) for Neb20 group compared to Neb10 group (81% [95% CI, 73-89]) and IV morphine group (79% [95% CI, 67-84]). The lowest resolution time was observed in Neb20 group (20 minutes [95% CI, 18-21]). Side effects were minor and significantly lower in both nebulization groups compared to IV morphine group. CONCLUSIONS: Nebulized morphine using boluses of 10 mg has similar efficacy and better safety than IV titrated morphine in patients with severe posttraumatic pain. Increasing nebulized boluses to 20 mg increases the effectiveness without increasing side effects. PMID- 26143314 TI - A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. AB - BACKGROUND: The aim of this study was to investigate a novel oxidative stress marker (thiol/disulphide homeostasis) in patients with acute myocardial infarction (AMI) and compare the results with healthy controls for the first time in literature. METHODS: A total of 450 participants including 300 patients with AMI and 150 healthy individuals were included in the study. Left ventricular ejection fraction, body mass index, peak troponin I levels, triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), native thiol, total thiol, and disulphide as well as disulphide/native thiol and disulphide/total thiol ratios were compared between the groups. RESULTS: There were significant differences between AMI patients and the controls for left ventricular ejection fraction and troponin, HDL, native thiol, total thiol, and disulphide levels as well as disulphide/native thiol and disulphide/total thiol ratios (P < .05). Stepwise logistic regression model indicated that HDL (odds ratio [OR] = 0.923, P < .001) and disulphide levels (OR = 0.548, P < .001) and disulphide/total thiol ratio (OR = 0.356, P < .001) were significantly and independently related to AMI. The cutoff value of disulphide/total thiol ratio percentage on admission to predict AMI in all population was 4.3, with a sensitivity of 70% and a specificity of 69%. CONCLUSION: Thiol/disulphide homeostasis may be used as a novel oxidative stress marker in patients with AMI because it is readily available, easily calculated, and relatively cheap. Further studies are needed to confirm the pathophysiologic role of thiol/disulphide homeostasis in AMI. PMID- 26143315 TI - Evaluation of fixed dose 4-factor prothrombin complex concentrate for emergent warfarin reversal. AB - OBJECTIVES: Four-factor prothrombin complex concentrates (4FPCCs) are emerging as the standard of care for emergent warfarin reversal due to their ability to rapidly and effectively achieve hemostasis. The ideal dose of this medication is not known. Recently, our hospital instituted a protocol where all doses of 4FPCC were a fixed dose of 1500 IU. This protocol provides 4FPCC rapidly and precludes delay waiting for international normalized ratio (INR) values. The purpose of this study was to evaluate our experience with this fixed dose protocol. METHODS: This is a retrospective review of patients who received 1500 IU of 4FPCC for emergent warfarin reversal between March 2014 and January 2015. Demographic and clinical data regarding administration, efficacy, and safety were collected and analyzed. RESULTS: A total of 39 patients met inclusion criteria. The most common indication for treatment was intracranial hemorrhage (28, 71.8%). The median INR at presentation was 3.3, and the median INR after a single dose of 1500 IU was 1.4 (P < .001). A total of 36 patients (92.3%) achieved successful reversal with a target INR of less than 2.0, and 28 patients (71.8%) achieved successful reversal with a target INR of 1.5 or less. There were no thrombotic adverse events within 7 days. CONCLUSIONS: Administration of a fixed dose of 1500 IU of 4FPCC leads to high rates of successful INR reversal and no related thrombotic adverse events within 7 days, and there was no need to wait for INR at presentation. These findings suggest good efficacy and safety when using 1500 IU of 4FPCC for emergent warfarin reversal. PMID- 26143316 TI - Takotsubo cardiomyopathy, sepsis and clinical outcome: does gender matter? PMID- 26143317 TI - Risk of thromboembolic events after protocolized warfarin reversal with 3-factor PCC and factor VIIa. AB - Bleeding events and life-threatening hemorrhage are the most feared complications of warfarin therapy. Prompt anticoagulant reversal aimed at replacement of vitamin K-dependent clotting factors is essential to promote hemostasis. A retrospective cohort study of warfarin-treated patients experiencing a life threatening hemorrhage treated with an institution-specific warfarin reversal protocol (postimplementation group) and those who received the prior standard of care (preimplementation group) was performed. The reversal protocol included vitamin K, 3-factor prothrombin complex concentrate, and recombinant factor VIIa. Demographic and clinical information, anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. A total of 227 patients were included in final analysis, 109 in the preimplementation group and 118 in the postimplementation group. Baseline patient characteristics were similar in both groups, with the exception of higher average Sequential Organ Failure Assessment scores in the postimplementation group (P = .0005). The most common indication for anticoagulation reversal was intraparenchymal hemorrhage. Prereversal international normalized ratios (INRs) were similar in both groups. Attainment of INR normalization to less than 1.4 was higher, and rebound INR was lower in the postimplementation group (P < .0001; P = .0013). Thromboembolic complications were significantly higher in the postimplementation group (P = .003). Elevated baseline Sequential Organ Failure Assessment score and mechanical valve as an indication for anticoagulation were independently associated with thrombotic complications (P = .005). A warfarin reversal protocol consisting of 3 factor prothrombin complex concentrate, recombinant factor VIIa, and vitamin K more consistently normalized INR values to less than 1.4 as compared to the prior standard of care in a diverse patient population. This success came at the cost of a 2-fold increase in risk of thromboembolic complications. PMID- 26143318 TI - Petal-like CdS nanospheres-based electrochemiluminescence aptasensor for detection of IgE with gold nanoparticles amplification. AB - A facile label-free electrochemiluminescence (ECL) aptasensor was designed for sensitive detection of human immunoglobulin E (IgE) using petal-like CdS nanospheres and Au nanoparticles (AuNPs) as sensing platform. To construct the aptasensor, petal-like CdS nanospheres as ECL emitter were firstly synthesized and immobilized on the chitosan-coated glassy carbon electrode (GCE) surface. Chitosan was coated on the CdS/CS/GCE again with two coating numbers to produce a stable ECL signal and facilitate subsequent AuNPs immobilization. The construction of aptasensor was achieved after IgE aptamer was adsorbed onto the AuNPs. The detection of IgE was performed upon the incubation of the interface with target protein IgE. Under the optimum conditions, the ECL signal decreased depending linearly on the logarithmic value of IgE concentration ranging from 5.0*10(-13) to 1.0*10(-9)M with a regression equation of I=-15254.8-2129.3 logc (R(2)=0.996). The detection limit was experimentally found to be 8.0*10(-14)M. The applicability of the constructed aptasensor was demonstrated in the determination of IgE in human serum samples. PMID- 26143319 TI - Measurement of non-sugar solids content in Chinese rice wine using near infrared spectroscopy combined with an efficient characteristic variables selection algorithm. AB - The non-sugar solids (NSS) content is one of the most important nutrition indicators of Chinese rice wine. This study proposed a rapid method for the measurement of NSS content in Chinese rice wine using near infrared (NIR) spectroscopy. We also systemically studied the efficient spectral variables selection algorithms that have to go through modeling. A new algorithm of synergy interval partial least square with competitive adaptive reweighted sampling (Si CARS-PLS) was proposed for modeling. The performance of the final model was back evaluated using root mean square error of calibration (RMSEC) and correlation coefficient (Rc) in calibration set and similarly tested by mean square error of prediction (RMSEP) and correlation coefficient (Rp) in prediction set. The optimum model by Si-CARS-PLS algorithm was achieved when 7 PLS factors and 18 variables were included, and the results were as follows: Rc=0.95 and RMSEC=1.12 in the calibration set, Rp=0.95 and RMSEP=1.22 in the prediction set. In addition, Si-CARS-PLS algorithm showed its superiority when compared with the commonly used algorithms in multivariate calibration. This work demonstrated that NIR spectroscopy technique combined with a suitable multivariate calibration algorithm has a high potential in rapid measurement of NSS content in Chinese rice wine. PMID- 26143320 TI - Continuous wavelet transform-based feature selection applied to near-infrared spectral diagnosis of cancer. AB - Spectrum is inherently local in nature since it can be thought of as a signal being composed of various frequency components. Wavelet transform (WT) is a powerful tool that partitions a signal into components with different frequency. The property of multi-resolution enables WT a very effective and natural tool for analyzing spectrum-like signal. In this study, a continuous wavelet transform (CWT)-based variable selection procedure was proposed to search for a set of informative wavelet coefficients for constructing a near-infrared (NIR) spectral diagnosis model of cancer. The CWT provided a fine multi-resolution feature space for selecting best predictors. A measure of discriminating power (DP) was defined to evaluate the coefficients. Partial least squares-discriminant analysis (PLS DA) was used as the classification algorithm. A NIR spectral dataset associated to cancer diagnosis was used for experiment. The optimal results obtained correspond to the wavelet of db2. It revealed that on condition of having better performance on the training set, the optimal PLS-DA model using only 40 wavelet coefficients in 10 scales achieved the same performance as the one using all the variables in the original space on the test set: an overall accuracy of 93.8%, sensitivity of 92.5% and specificity of 96.3%. It confirms that the CWT-based feature selection coupled with PLS-DA is feasible and effective for constructing models of diagnostic cancer by NIR spectroscopy. PMID- 26143321 TI - Evans hole and non linear optical activity in Bis(melaminium) sulphate dihydrate: A vibrational spectral study. AB - Bis(melaminium) sulphate dihydrate (BMSD), an interesting melaminium derivative for nonlinear optical activity, has been subjected to vibrational spectral analysis using FT IR and FT Raman spectra. The analysis has been aided by the Potential Energy Distribution (PED) of vibrational spectral bands, derived using density functional theory (DFT) at B3LYP/6-31G(d) level. The geometry is found to correlate well with the XRD structure and the band profiles for certain vibrations in the finger print region have been theoretically explained using Evans hole. The detailed Natural Bond Orbital (NBO) analysis of the hydrogen bonding in BMSD has also been carried out to understand the correlation between the stabilization energy of hyperconjugation of the lone pair of donor with the sigma(*) orbital of hydrogen-acceptor bond and the strength of hydrogen bond. The theoretical calculation shows that BMSD has NLO efficiency, 2.66 times that of urea. The frontier molecular orbital analysis points to a charge transfer, which contributes to NLO activity, through N-H...O intermolecular hydrogen bonding between the melaminium ring and the sulphate. The molecular electrostatic potential (MEP) mapping has also been performed for the detailed analysis of the mutual interactions between melaminium ring and sulphate ion. PMID- 26143322 TI - Fluorescence enhancement effect of Eu(III)-thenoyltrifluoroacetone-cetyltrimethyl ammonium bromide in water-dissolved organic matter extracted from wheat straw. AB - The fluorescence spectral characteristics of water-dissolved organic matter extracted from wheat straw (DOM-WS) were studied using three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy. The results indicated that 3D-EEM spectra of DOM-WS showed four different fluorophores: humic like, visible fulvic-like, UV fulvic-like and protein-like substances. It is interesting that DOM-WS can obviously enhance the fluorescence intensity of Eu(III)-thenoyltrifluoroacetone-cetyltrimethyl ammonium bromide system. On the basis of this study, a new fluorescence method for the determination of trace amounts of Eu(III) was developed. Under the optimal conditions, the enhanced fluorescence intensity was in proportion to the concentration of Eu(III) in the range of 8.0*10(-8)-8.0*10(-7)mol/L. The detection limit (S/N=3) was 1.1*10( 9)mol/L. This method was applied to the analysis of Eu(III) concentration in standard sample and obtained satisfactory results. It may be a new way to use wheat straw effectively. PMID- 26143323 TI - Resonance Rayleigh scattering method for determination of 2-mercaptobenzothiazole using gold nanoparticles probe. AB - A sensitive, simple and novel method was developed to determine 2 mercaptobenzothiazole (2MBT) in water samples. This method was based on the interaction between gold nanoparticles (AuNPs) and 2MBT followed by increasing of the resonance Rayleigh scattering (RRS) intensity of nanoparticles. The change in RRS intensity (DeltaIRRS) was linearly correlated to the concentration of 2MBT over the ranges of 5.0-100.0 and 100.0-300.0 MUg L(-1). 2MBT can be measured in a short time (5 min) without any complicated or time-consuming sample pretreatment process. Parameters that affect the RRS intensities such as pH, concentration of AuNPs, standing time, electrolyte concentration, and coexisting substances were systematically investigated and optimized. Interference tests showed that the developed method has a very good selectivity and could be used conveniently for determination of 2MBT. The limit of detection (LOD) and limit of quantification (LOQ) were 1.0 and 3.0 MUg L(-1), respectively. Relative standard deviations (RSD) for 20.0 and 80.0 MUg L(-1) of 2MBT were 1.1 and 2.3, respectively. Possible mechanisms for the RRS changes of AuNPs in the presence of 2MBT were discussed and the method was successfully applied for the analysis of real water samples. PMID- 26143324 TI - Dual-channel detection of metallothioneins and mercury based on a mercury mediated aptamer beacon using thymidine-mercury-thymidine complex as a quencher. AB - A novel dual-channel strategy for the detection of metallothioneins (MTs) and Hg(2+) has been developed based on a mercury-mediated aptamer beacon (MAB) using thymidine-mercury-thymidine complex as a quencher for the first time. In the presence of Hg(2+), the T-rich oligonucleotide with a 6-carboxyfluorescein (TRO FAM) can form an aptamer beacon via the formation of T-Hg(2+)-T base pairs, which results in a fluorescence quenching of the sensing system owing to the fluorescence resonance energy transfer (FRET) from the fluorophore of FAM to the terminated T-Hg(2+)-T base pair. The addition of MTs into this solution leads to the disruption of the T-Hg(2+)-T complex, resulting in an increase of the fluorescent signal of the system. In the optimizing condition, DeltaF was directly proportional to the concentrations ranging from 5.63 nM to 0.275 MUM for MTs, and 14.2 nM to 0.30 MUM for Hg(2+) with the detection limits of 1.69 nM and 4.28 nM, respectively. The proposed dual-channel method avoids the label steps of a quencher in common molecular beacon strategies, without tedious procedure or the requirement of sophisticated equipment, and is rapid, inexpensive and sensitive. PMID- 26143325 TI - Synthesis, characterization, DNA binding and catalytic applications of Ru(III) complexes. AB - A new series of azodye ligands 5-chloro-3-hydroxy-4-(aryldiazenyl)pyridin-2(1H) one (HLn) were synthesized by coupling of 5-chloro-3-hydroxypyridin-2(1H)-one with aniline and its p-derivatives. These ligands and their Ru(III) complexes of the type trans-[Ru(Ln)2(AsPh3)2]Cl were characterized by elemental analyses, IR, (1)H NMR and UV-Visible spectra as well as magnetic and thermal measurements. The molar conductance measurements proved that all the complexes are electrolytes. IR spectra show that the ligands (HLn) acts as a monobasic bidentate ligand by coordinating via the nitrogen atom of the azo group (NN) and oxygen atom of the deprotonated phenolic OH group, thereby forming a six-membered chelating ring and concomitant formation of an intramolecular hydrogen bond. The molecular and electronic structures of the investigated compounds (HLn) were also studied using quantum chemical calculations. The calf thymus DNA binding activity of the ligands (HLn) and their Ru(III) complexes were studied by absorption spectra and viscosity measurements. The mechanism and the catalytic oxidation of benzyl alcohol by trans-[Ru(Ln)2(AsPh3)2]Cl with hydrogen peroxide as co-oxidant were described. PMID- 26143326 TI - Vibrational spectroscopic and molecular docking study of (2E)-N-(4-chloro-2-oxo 1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide. AB - FT-IR and FT-Raman spectra of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3 phenylprop-2-enamide were recorded and analyzed experimentally and theoretically. The synthesis, (1)H NMR and PES scan results are also discussed. Nonlinear optical behavior of the examined molecule was investigated by the determination of first hyperpolarizability. The calculated HOMO and LUMO energies show the chemical activity of the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. From the MEP it is evident that the negative charge covers the carbonyl group and the positive region is over the NH group. The calculated geometrical parameters (SDD) are in agreement with that of similar derivatives. Molecular docking simulations against targets from Mycobacterium tuberculosis are reported and the results suggest that the compound might exhibit inhibitory activity against PknB. PMID- 26143327 TI - Molecular conformational analysis, vibrational spectra, NBO, NLO analysis and molecular docking study of bis[(E)-anthranyl-9-acrylic]anhydride based on density functional theory calculations. AB - FT-IR and FT-Raman spectra of bis[(E)-anthranyl-9-acrylic]anhydride were recorded and analyzed. The conformational behavior is also investigated. The vibrational wave numbers were calculated using density functional theory (DFT) quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in Infrared and Raman spectra. Potential energy distribution was done using GAR2PED program. The geometrical parameters are compared with related structures. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using Natural Bonding Orbital (NBO) analysis. The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) analysis are used to determine the charge transfer within the molecule. Molecular Electrostatic Potential (MEP) was performed by the DFT method. The calculated first hyperpolarizability of the title compound is comparable with the reported values of similar derivatives and is 4.23 times that of the standard nonlinear optical (NLO) material urea and the title compound and its derivatives are an attractive object for future studies of nonlinear optical properties. To evaluate the in silico antitumor activity of the title compound molecular docking studies were carried out against protein Bcl-xL. The (1)H-NMR spectrum is also reported. PMID- 26143328 TI - Supramolecular interaction of gemifloxacin and hydroxyl propyl beta-cyclodextrin spectroscopic characterization, molecular modeling and analytical application. AB - The solid inclusion complex of gemifloxacin (GFX) and hydroxyl propyl beta cyclodextrin (HPbeta-CD) was prepared and examined by UV-visible, FTIR, NMR, electrospray ionization mass spectrometry (ESI-MS) and fluorescence spectroscopy. The formation of inclusion complex has been confirmed on the basis of changes of spectroscopic properties. Further the interaction between GFX and HPbeta-CD was studied using molecular modeling approaches. The results showed that HPbetaCD reacted with GFX to form a 1:1 host-guest inclusion complex. Based on the enhancement of the fluorescence intensity of GFX produced through complex formation, a simple, accurate, rapid and highly sensitive spectrofluorometric method for the determination of GFX in pharmaceutical formulation was developed. The linear relationships between the intensity and GFX concentration was obtained in the concentration range of 20-140 ng/mL with good correlation coefficients (0.9997). The limit of detection (LOD) was found to be 4 ng/mL. The proposed method was successfully applied to the analysis of GFX in pharmaceutical preparation. PMID- 26143329 TI - A DFT/TDDFT investigation of the excited state proton transfer reaction of fisetin chromophore. AB - In the present work, 3, 3', 4', 7-tetrahydroxyflavone (fisetin), as one of the most extensive distributed flavonoids, has been investigated on the excited state proton transfer (ESPT) based on the time-dependent density functional theory (TDDFT) method. The calculated absorption and fluorescence spectra based on the TDDFT method are in agreement with the experimental results. Two kinds of structures of fisetin chromophore are found in the first excited (S1) state, which may be due to the proton transfer reactive. Hydrogen bond strengthening has been testified in the S1 state based on comparing staple bond lengths and bond angles involved in hydrogen bonding between the S0 state and the S1 state. In addition, the calculated infrared spectra at the O-H stretching vibrational region and calculated hydrogen bond energy also declare the phenomenon of hydrogen bond strengthening. The frontier molecular orbitals (MOs) analysis and Natural bond orbital (NBO) manifest the intramolecular charge transfer of fisetin chromophore, which reveals the tendency of proton transfer. The potential energy surfaces of the S0 and S1 states are constructed to explain the mechanism of the proton transfer in excited state in detail. PMID- 26143330 TI - Vibrationally resolved 1Lb (1A')<->S0 (1A') electronic spectra of benzimidazole and indene: Influence of Duschinsky and Herzberg-Teller effects on weak dipole allowed transitions. AB - Geometrical optimizations of the ground and first excited states of benzimidazole and indene were performed using the density functional theory (DFT) and its time dependent extension methods (TD-DFT), respectively. Their vibrationally resolved (1)Lb ((1)A')<->S0 ((1)A') absorption and fluorescence spectra were simulated within the Franck-Condon approximation including the Herzberg-Teller (HT) and Duschinsky effects. Calculated results revealed that, with the HT and Duschinsky effects getting involved, the simulated weak (1)Lb ((1)A')<->S0 ((1)A') electronic spectra of the two molecules excellently reproduce the experimental findings. Based on the experimental data and other theoretical results, we tentatively assigned most of the vibrational normal modes which emerged in the experimental spectra of the two molecules. The present theoretical insights are expected to help us understand the nature of electronic transitions in the vibrationally resolved absorption and fluorescence spectra of benzimidazole and its analogues. PMID- 26143331 TI - Near-infrared long-persistent phosphor of Zn3Ga 2Ge 2O10: Cr3+ sintered in different atmosphere. AB - A variety of materials sintered in different atmosphere have been well investigated, but there are few reports on the long-persistent phosphorescent materials, especially the near-infrared long-persistent phosphorescent materials sintered in various atmosphere. Changing the surrounding atmosphere is an effective method to improve the afterglow properties of the materials. In this work, we fabricate a typical kind of near-infrared long-persistent phosphorescent materials of Zn3Ga2Ge2O10: 0.5% Cr(3+) in neutral, oxidizing, and reducing atmosphere. By analyzing the XRD patterns, afterglow spectra, decay and thermo luminescence curves, we discuss the great effects on the structure, long persistent properties and trap properties of the phosphor. This work of obtaining the Zn3Ga2Ge2O10: 0.5% Cr(3+) is of great potential in the applications in night vision surveillance and in vivo bio-imaging. PMID- 26143332 TI - Application and recognition behaviors of TPA-cored probes with subtle structural change. AB - Two new triphenylamine-cored probes (L1, L2) with different receptor units have been synthesized and fully characterized by IR, NMR and MS spectra. Their photophysical properties have been investigated in detail. The recognition abilities of two probes were evaluated by a series of metal ions, which showed that L1 could recognize Cu(2+) over other metal ions. L2 could respond to Cu(2+), Hg(2+) in a short time, which interferes with a little each other. The Job's plot and (1)H NMR titration of L1 with Cu(2+) and L2 with Cu(2+) (Hg(2+)) in CD3CN verified the coordination mode of complexes L1-Cu(2+), L2-Cu(2+) and L2-Hg(2+), respectively. The limit of detection of L2 for Cu(2+) was lower than that of L1 towards Cu(2+). The results demonstrated that the receptor units in the probes had remarkable effect on recognizing metal ions. Meanwhile, L1 and L2 showed potential application in bio-imaging after mixing with Cu(2+). PMID- 26143333 TI - Photophysical properties gallium octacarboxy phthalocyanines conjugated to CdSe@ZnS quantum dots. AB - L-Glutathione (GSH) capped core CdSe (2.3 nm) and core shell CdSe@ZnS quantum dots (QDs) (3.0 nm and 3.5 nm) were coordinated to gallium octacarboxy phthalocyanine (ClGaPc(COOH)8) to form ClGaPc(COOH)8-QDs conjugates. An efficient transfer of energy from the QDs to the Pcs was demonstrated through Forster resonance energy transfer (FRET), the FRET efficiencies in all cases was above 50%. The photophysical parameters (triplet state and fluorescence quantum yields and lifetimes) were also determined for the conjugates. There was a decrease in the fluorescence lifetimes of ClGaPc(COOH)8 in the presence of all the QDs, due to the heavy atom effect. The triplet quantum yields increased in the conjugates. The lifetimes also became longer for the conjugates compared to Pc alone. PMID- 26143334 TI - Pro-tumorigenic role of ERalpha in prostate cancer cells. PMID- 26143335 TI - C/EBPbeta and C/EBPdelta transcription factors: Basic biology and roles in the CNS. AB - CCAAT/enhancer binding protein (C/EBP) beta and C/EBPdelta are transcription factors of the basic-leucine zipper class which share phylogenetic, structural and functional features. In this review we first describe in depth their basic molecular biology which includes fascinating aspects such as the regulated use of alternative initiation codons in the C/EBPbeta mRNA. The physical interactions with multiple transcription factors which greatly opens the number of potentially regulated genes or the presence of at least five different types of post translational modifications are also remarkable molecular mechanisms that modulate C/EBPbeta and C/EBPdelta function. In the second part, we review the present knowledge on the localization, expression changes and physiological roles of C/EBPbeta and C/EBPdelta in neurons, astrocytes and microglia. We conclude that C/EBPbeta and C/EBPdelta share two unique features related to their role in the CNS: whereas in neurons they participate in memory formation and synaptic plasticity, in glial cells they regulate the pro-inflammatory program. Because of their role in neuroinflammation, C/EBPbeta and C/EBPdelta in microglia are potential targets for treatment of neurodegenerative disorders. Any strategy to reduce C/EBPbeta and C/EBPdelta activity in neuroinflammation needs to take into account its potential side-effects in neurons. Therefore, cell-specific treatments will be required for the successful application of this strategy. PMID- 26143336 TI - Loneliness of older people aged 70: a comparison of two Finnish cohorts born 20 years apart. AB - OBJECTIVE: This study aimed to examine loneliness among two birth cohorts, born 20 years apart, when they were 70 years of age, and to identify factors explaining loneliness. METHODS: The cohorts consisted of older home-dwelling residents of Turku, Finland, from the birth cohort 1920 in 1991 (N=1530) and the birth cohort 1940 in 2011 (N=1307). Suffering from loneliness was assessed with the question: 'Do you suffer from loneliness?' Cross-tabulations with chi-square test, general linear model (GLM) and multiple regression analysis were used in statistical testing and modeling. RESULTS: In the 1940 cohort, around one-fifth (18%) of the respondents suffered from loneliness at least sometimes, while the corresponding figure in the 1920 cohort was around one-fourth (26%). Our analyses indicated that the effect of cohort was not a statistically significant explanatory factor of loneliness. Living status, self-rated health and memory compared to age peers were statistically significant explanatory factors for suffering from loneliness. When we controlled the effect of depressiveness on the experience of loneliness, it was shown that the effects of living status and self rated health remained statistically significant, whereas memory compared to age peers did not. Depressiveness itself was highly important. The combined effect of living status and self-rated health emerged as the most significant explanatory factor for loneliness. Older people with poor self-rated health who lived alone were most likely to suffer from loneliness. CONCLUSION: The findings give healthcare professionals an opportunity to plan for interventions aimed at combating loneliness among home-dwelling older people. PMID- 26143337 TI - Consciousness, cognition and brain networks: New perspectives. AB - A detailed analysis of the literature on consciousness and cognition mechanisms based on the neural networks theory is presented. The immune and inflammatory response to the anesthetic-surgical procedure induces modulation of neuronal plasticity by influencing higher cognitive functions. Anesthetic drugs can cause unconsciousness, producing a functional disruption of cortical and thalamic cortical integration complex. The external and internal perceptions are processed through an intricate network of neural connections, involving the higher nervous activity centers, especially the cerebral cortex. This requires an integrated model, formed by neural networks and their interactions with highly specialized regions, through large-scale networks, which are distributed throughout the brain collecting information flow of these perceptions. Functional and effective connectivity between large-scale networks, are essential for consciousness, unconsciousness and cognition. It is what is called the "human connectome" or map neural networks. PMID- 26143338 TI - Effects of sevoflurane on ventilator induced lung injury in a healthy lung experimental model. AB - INTRODUCTION AND OBJECTIVE: Ventilator-induced lung injury (VILI) causes a systemic inflammatory response in tissues, with an increase in IL-1, IL-6 and TNF alpha in blood and tissues. Cytoprotective effects of sevoflurane in different experimental models are well known, and this protective effect can also be observed in VILI. The objective of this study was to assess the effects of sevoflurane in VILI. MATERIAL AND METHODS: A prospective, randomized, controlled study was designed. Twenty female rats were studied. The animals were mechanically ventilated, without sevoflurane in the control group and sevoflurane 3% in the treated group (SEV group). VILI was induced applying a maximal inspiratory pressure of 35 cmH2O for 20 min without any positive end-expiratory pressure for 20 min (INJURY time). The animals were then ventilated 30 min with a maximal inspiratory pressure of 12 cmH2O and 3 cmH2O positive end-expiratory pressure (time 30 min POST-INJURY), at which time the animals were euthanized and pathological and biomarkers studies were performed. Heart rate, invasive blood pressure, pH, PaO2, and PaCO2 were recorded. The lung wet-to-dry weight ratio was used as an index of lung edema. RESULTS: No differences were found in the blood gas analysis parameters or heart rate between the 2 groups. Blood pressure was statistically higher in the control group, but still within the normal clinical range. The percentage of pulmonary edema and concentrations of TNF-alpha and IL-6 in lung tissue in the SEV group were lower than in the control group. CONCLUSIONS: Sevoflurane attenuates VILI in a previous healthy lung in an experimental subclinical model in rats. PMID- 26143339 TI - Assessment of acid-base balance. Stewart's approach. AB - The study of acid-base equilibrium, its regulation and its interpretation have been a source of debate since the beginning of 20th century. Most accepted and commonly used analyses are based on pH, a notion first introduced by Sorensen in 1909, and on the Henderson-Hasselbalch equation (1916). Since then new concepts have been development in order to complete and make easier the understanding of acid-base disorders. In the early 1980's Peter Stewart brought the traditional interpretation of acid-base disturbances into question and proposed a new method. This innovative approach seems more suitable for studying acid-base abnormalities in critically ill patients. The aim of this paper is to update acid-base concepts, methods, limitations and applications. PMID- 26143340 TI - Auditory cortex directs the input-specific remodeling of thalamus. AB - Input-specific remodeling is observed both in the primary auditory cortex (AI) and the ventral division of the medial geniculate body of the thalamus (MGBv) through motivation such as learning. Here, we show the role of AI in the MGBv remodeling induced by the electrical stimulation (ES) of the central division of the inferior colliculus (ICc). For the MGBv neurons with frequency tunings different from those of electrically stimulated ICc neurons, their frequency tunings shifted towards the tunings of the ICc neurons. AI neurons also showed this input-specific remodeling after ES of the ICc (ESICc). Interestingly, the input-specific remodeling of MGBv was eliminated when the AI was inactivated using cortical application of muscimol. For the MGBv neurons tuned to the same frequency as the stimulated ICc neurons, their tunings were kept but their responses were facilitated after the ESICc. In contrast to the input-specific tuning shifts, this facilitation was rarely impacted by the AI inactivation. Thus, we conclude that AI directs the input-specific remodeling of MGBv induced by ESICc. It is suggested that the tuning shift in the MGBv primarily takes place in the AI and is relayed to the MGBv through the corticofugal system while the MGBv mainly highlights the frequency information emphasized in ICc. PMID- 26143341 TI - Anti-growth effect of a novel trans-dichloridobis[2-(2 hydroxyethyl)pyridine]platinum (II) complex via induction of apoptosis on breast cancer cell lines. AB - Breast cancer still continues to be the leading cause of cancer-related mortality in women worldwide. Although advances have been made in the treatment of this disease during the past decade, new approaches and novel compounds are urgently needed. The aim of this study was to evaluate the cytotoxic activity of trans [PtCl2(2-hepy)2] [2-hepy=2-(2-hydroxyethyl) pyridine] on breast cancer cell lines, MCF-7 and MDA-MB-231. The platinum (II) complex was synthesized and characterized by our laboratory working group. Anti-growth effect was assayed by the MTT and ATP viability assays and also monitored real-time using xCELLigence system. The mode of cell death was evaluated by using the fluorescence microscopy (Hoechst 33342+Calcein-AM+Propidium iodide staining), Western blotting (cleaved PARP and caspase 3, total caspase 8), flow cytometry (quantitative analysis of live, early/late apoptotic, dead cells and caspase 3/7 activity) and the RT-PCR (the genes analyzed were BCL-2L10, BIK, BAX, BCL-2, FASLG, HRK, TNFRSF10B, and TNFRSF10A). The platinum (II) complex had anti-growth effect in a dose dependent manner in vitro. Cells were killed by apoptosis as evidenced by the pyknotic nuclei, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active caspase-3. These results suggest that the complex might represent a potentially active novel drug for the breast cancer treatment and warrants further studies due to its promising cytotoxic activity. PMID- 26143342 TI - Lactobacillus paracasei Induces M2-Dominant Kupffer Cell Polarization in a Mouse Model of Nonalcoholic Steatohepatitis. AB - BACKGROUND AND AIMS: Gut microbiota may be associated with the pathogenesis of nonalcoholic steatohepatitis (NASH). This study aimed to investigate the protective effects and possible mechanisms of Lactobacillus paracasei on NASH. METHODS: Thirty male C57BL/6 mice were randomized into three groups and maintained for 10 weeks: control group (standard chow), NASH model group (high fat + 10 % fructose diet), and the L. paracasei group (NASH model with L. paracasei). Liver histology, serum aminotransferase levels, and hepatic gene expression levels were measured. Intestinal permeability was investigated using urinary (51)Creatinine Ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance. Total Kupffer cell counts and their composition (M1 vs. M2 Kupffer cells) were measured using flow cytometry with F4/80 and CD206 antibodies. RESULTS: Hepatic fat deposition, serum ALT level, and (51)Cr-EDTA clearance were significantly lower in the L. paracasei group than the NASH group (p < 0.05). The L. paracasei group had lower expression in Toll-like receptor-4 (TLR-4), NADPH oxidase-4 (NOX 4), tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP 1), interleukin 4 (IL-4), peroxisome proliferator activated receptor gamma (PPAR gamma), and PPAR-delta compared with the NASH group (p < 0.05). The total number of F4/80(+) Kupffer cells was lower in the L. paracasei group than the NASH group. L. paracasei induced the fraction of F4/80(+)CD206(+) cells (M2 Kupffer cells) while F4/80(+)CD206(-) cells (M1 Kupffer cells) were higher in the NASH group (F4/80(+)CD206(+) cell: 44% in NASH model group vs. 62% in L. paracasei group, p < 0.05). CONCLUSIONS: Lactobacillus paracasei attenuates hepatic steatosis with M2-dominant Kupffer cell polarization in a NASH model. PMID- 26143344 TI - A concise overview of advances in therapeutic efficacy of serum eye drops and their alternatives to treat dry eye syndrome: Verifying the narratives of clinical consistency beyond the periphery of international inconsistency on the methods of collection and application. PMID- 26143343 TI - Pharmacokinetics and Tolerability of Intravenous Sildenafil in Two Subjects with Child-Turcotte-Pugh Class C Cirrhosis and Renal Dysfunction. PMID- 26143345 TI - The serological and genetic characterization of CisAB blood group in a Chinese family. AB - BACKGROUND: The rare CisAB blood genotype results in the inheritance of both the A and B blood types from a single parent. Several CisAB blood type phenotypes have been characterized that differ in their serological reactions and in the activities of the gene-encoded blood group A and B transferases. In this study, we conducted serological and genetic analyses of a Chinese family with four CisAB carrying members. STUDY DESIGN AND METHODS: A 10-year-old girl was suspected to have the CisAB blood type when forward blood typing indicated that she was blood type AB but reverse blood typing indicated that she was blood type A. An examination of this family identified that four of ten family members across three generations had a pattern of AB inheritance that could be explained only by the inheritance of the CisAB genotype. Blood samples from the family were tested serologically and genetically using PCR-SSP for the relevant CisAB alleles. The samples that were suitable for DNA analysis were sequenced for potential mutations. RESULTS: Of the ten family members included in this study, four members showed mismatched forward and reverse blood grouping results, four members typed as blood group O and the remaining two members typed as blood group B. Among the four mismatched individuals, the propositus and her mother's mother were serologically typed as having the A2B3 phenotype. The propositus' mother and her mother's brother were typed as having the A2B phenotype, and had the genotypes CisAB01/O02 and CisAB01/B101, respectively. Further sequencing analysis of the four samples with the CisAB blood type revealed that a G(261) deletion occurred along with 297A>G, 467C>T, 646T>A, 681G>A, 771C>T, 803G>C and 829G>C substitutions in exons 6 and 7 of CisAB01/O02, while a 297A>G substitution occurred in exon 6 and 467C>T, 803G>C, 526C>G, 657C>T, 703G>A, 796C>A, 930G>A substitutions occurred in exon 7 of CisAB01/B101. CONCLUSION: A family was identified in which 4/10 family members across three generations had inherited the CisAB blood group. Two of the CisAB genotypes were further identified as CisAB01/O02 and CisAB01/B101. The CisAB heterozygous alleles contributed to the different phenotypes that were observed. PMID- 26143346 TI - A multiplex real-time PCR assay for routine diagnosis of bacterial vaginosis. AB - A semi-quantitative multiplex PCR assay for the diagnosis of bacterial vaginosis (BV) was evaluated in a prospective study in a population of Dutch women with complaints of abnormal vaginal discharge. The PCR targets Gardnerella vaginalis, Atopobium vaginae, Megasphaera phylotype 1, Lactobacillus crispatus and Lactobacillus iners. Together with a short questionnaire, a vaginal swab for PCR and vaginal smear for microscopy were taken by their general practitioner or gynaecologist. Data from 151 women (median age 32) were available. Nugent Score (NS) was used to classify the samples and 83 samples were classified as normal (NS 0-3), 13 as intermediate (NS 4-6), and 55 as bacterial vaginosis (NS 7-10). In women with a NS of 7-10, PCR detected Gardnerella vaginalis, Atopobium vaginae and Megasphaera phylotype 1 in respectively, 96 %, 87 % and 60 %, whereas in women with a NS of 1-3 these species were detected in 27 %, 6 % and 2 % (P <0.001). A ratio of Lactobacillus crispatus over Lactobacillus iners of <1 (as calculated from the quantification cycle value (Cq)) was present in women with a NS of 7-10 in 66 % versus 33 % in women with a NS of 1-3 (P <0.001). The BV-PCR displayed a sensitivity of 92 % and specificity of 96 % with a positive predictive value of 94 % and a negative predictive value of 95 %. The Lactobacillus-index improved the correct classification of samples where only one of the other bacterial species was detected. Compared to the Nugent Score this multiplex qPCR offers a convenient tool for performing observer independent diagnosis of BV. PMID- 26143347 TI - Direct molecular versus culture-based assessment of Gram-positive cocci in biopsies of patients with major abscesses and diabetic foot infections. AB - Major abscesses and diabetic foot infections (DFIs) are predominant subtypes of complicated skin and skin structure infections (cSSSIs), and are mainly caused by Staphylococcus aureus and beta-hemolytic streptococci. This study evaluates the potential benefit of direct pathogen-specific real-time polymerase chain reaction (PCR) assays in the identification of causative organisms of cSSSIs. One-hundred and fifty major abscess and 128 DFI biopsy samples were collected and microbial DNA was extracted by using the Universal Microbe Detection kit for tissue samples. Pathogen-specific PCRs were developed for S. aureus and its virulence factor Panton-Valentine leukocidin (PVL), Streptococcus pyogenes, S. agalactiae, S. dysgalactiae, and the S. anginosus group. Identification by pathogen-specific PCRs was compared to routine culture and both methods were considered as the gold standard for determination of the sensitivity and specificity of each assay. Direct real-time PCR assays of biopsy samples resulted in a 34 % higher detection of S. aureus, 37 % higher detection of S. pyogenes, 18 % higher detection of S. agalactiae, 4 % higher detection of S. dysgalactiae subspecies equisimilis, and 7 % higher detection of the S. anginosus group, compared to routine bacterial culture. The presence of PVL was mainly confined to S. aureus isolated from major abscess but not DFI biopsy samples. In conclusion, our pathogen-specific real time PCR assays had a higher yield than culture methods and could be an additional method for the detection of relevant causative pathogens in biopsies. PMID- 26143348 TI - A three-point time series study of antibiotic usage on an intensive care unit, following an antibiotic stewardship programme, after an outbreak of multi resistant Acinetobacter baumannii. AB - Antibiotic use in intensive care units (ICUs) can promote antimicrobial resistance. Outbreaks of multi-resistant bacteria significantly affect patient outcomes and delivery of care. Antibiotic stewardship programmes (ASPs), combining root-cause analyses and multi-faceted prevention strategies, are necessary, often at significant cost and time. Which elements of such strategies have the largest impact on antibiotic usage following an outbreak is unclear. The aim of this study was to investigate how antibiotic usage in a university hospital ICU changed with a non-protocolised ASP following a disruptive outbreak of multi-resistant Acinetobacter baumannii (MRAB). This was a three time-period observational cohort study. The primary endpoint was the change in overall antibiotic usage (daily defined dose, DDD, antibiotic-days, antibiotic-courses) for consecutive ICU patients staying >48 h, over three 6-month study time periods pre-MRAB (2008, n = 84) and post-MRAB (2010, n = 88; 2012, n = 122). Secondary endpoints were changes in antibiotic usage and patient demographics, in predefined admission categories (Medical Emergency, ME; Surgical Elective, SEL; and Surgical Emergency, SE). The mean age (54.6 +/- 17.7, 58.1 +/- 17.9, 62.8 +/- 19.1 years*) and severity of illness (APACHE 14.8 +/- 8.0, 16.7 +/- 6.8, 18.3 +/- 6.1*) increased, particularly medical admissions. There was a sustained reduction in DDD antibiotic usage [1895.1 (2008), 1224.2 (2010), 1236.6 (2012) per 1000 patient-days] but no overall change in antibiotic-days or antibiotic-courses. Antibiotic usage (antibiotic-days) fell significantly in surgical emergency admissions [20.2 +/- 32.1, 4.6 +/- 7.4*, 5.9 +/- 7.3]. There was a sustained drop in beta-lactam, quinolone, glycopeptide and macrolide usage. Following an MRAB outbreak, and subsequent operational changes including enhanced ASPs (non protocolised), there was a sustained overall fall in antibiotic usage in spite of an increase in disease severity over 5 years. PMID- 26143349 TI - Thermal acclimation and thyroxine treatment modify the electric organ discharge frequency in an electric fish, Apteronotus leptorhynchus. AB - In ectotherms, the rate of many neural processes is determined externally, by the influence of the thermal environment on body temperature, and internally, by hormones secreted from the thyroid gland. Through thermal acclimation, animals can buffer the influence of the thermal environment by adjusting their physiology to stabilize certain processes in the face of environmental temperature change. The electric organ discharge (EOD) used by weak electric fish for electrocommunication and electrolocation is highly temperature sensitive. In some temperate species that naturally experience large seasonal fluctuations in environmental temperature, the thermal sensitivity (Q10) of the EOD shifts after long-term temperature change. We examined thermal acclimation of EOD frequency in a tropical electric fish, Apteronotus leptorhynchus that naturally experiences much less temperature change. We transferred fish between thermal environments (25.3 and 27.8 degrees C) and measured EOD frequency and its thermal sensitivity (Q10) over 11 d. After 6d, fish exhibited thermal acclimation to both warming and cooling, adjusting the thermal dependence of EOD frequency to partially compensate for the small change (2.5 degrees C) in water temperature. In addition, we evaluated the thyroid influence on EOD frequency by treating fish with thyroxine or the anti-thyroid compound propylthiouricil (PTU) to stimulate or inhibit thyroid activity, respectively. Thyroxine treatment significantly increased EOD frequency, but PTU had no effect. Neither thyroxine nor PTU treatment influenced the thermal sensitivity (Q10) of EOD frequency during acute temperature change. Thus, the EOD of Apteronotus shows significant thermal acclimation and responds to elevated thyroxine. PMID- 26143350 TI - In situ compressibility of carbonated hydroxyapatite in tooth dentine measured under hydrostatic pressure by high energy X-ray diffraction. AB - Tooth dentine and other bone-like materials contain carbonated hydroxyapatite nanoparticles within a network of collagen fibrils. It is widely assumed that the elastic properties of biogenic hydroxyapatites are identical to those of geological apatite. By applying hydrostatic pressure and by in situ measurements of the a- and c- lattice parameters using high energy X-ray diffraction, we characterize the anisotropic deformability of the mineral in the crowns and roots of teeth. The collected data allowed us to calculate the bulk modulus and to derive precise estimates of Young's moduli and Poisson's ratios of the biogenic mineral particles. The results show that the dentine apatite particles are about 20% less stiff than geological and synthetic apatites and that the mineral has an average bulk modulus K=82.7 GPa. A 5% anisotropy is observed in the derived values of Young's moduli, with E11~91 GPa and E33~96 GPa, indicating that the nanoparticles are only slightly stiffer along their long axis. Poisson's ratio spans nu~0.30-0.35, as expected. Our findings suggest that the carbonated nanoparticles of biogenic apatite are significantly softer than previously thought and that their elastic properties can be considered to be nearly isotropic. PMID- 26143351 TI - Failure mechanisms of additively manufactured porous biomaterials: Effects of porosity and type of unit cell. AB - Since the advent of additive manufacturing techniques, regular porous biomaterials have emerged as promising candidates for tissue engineering scaffolds owing to their controllable pore architecture and feasibility in producing scaffolds from a variety of biomaterials. The architecture of scaffolds could be designed to achieve similar mechanical properties as in the host bone tissue, thereby avoiding issues such as stress shielding in bone replacement procedure. In this paper, the deformation and failure mechanisms of porous titanium (Ti6Al4V) biomaterials manufactured by selective laser melting from two different types of repeating unit cells, namely cubic and diamond lattice structures, with four different porosities are studied. The mechanical behavior of the above-mentioned porous biomaterials was studied using finite element models. The computational results were compared with the experimental findings from a previous study of ours. The Johnson-Cook plasticity and damage model was implemented in the finite element models to simulate the failure of the additively manufactured scaffolds under compression. The computationally predicted stress-strain curves were compared with the experimental ones. The computational models incorporating the Johnson-Cook damage model could predict the plateau stress and maximum stress at the first peak with less than 18% error. Moreover, the computationally predicted deformation modes were in good agreement with the results of scaling law analysis. A layer-by-layer failure mechanism was found for the stretch-dominated structures, i.e. structures made from the cubic unit cell, while the failure of the bending-dominated structures, i.e. structures made from the diamond unit cells, was accompanied by the shearing bands of 45 degrees . PMID- 26143352 TI - Mechanical properties and permeability of porous chitosan-poly(p-dioxanone)/silk fibroin conduits used for peripheral nerve repair. AB - Some poly(p-dioxanone) (PDO) homopolymers were first synthesized and the selected PDO was conjugated onto chitosan using a group-protecting method to produce chitosan-poly(p-dioxanone) (CH-PDO) copolymers with various PDO percentages changing from around 30 to 60 wt%. The CH-PDO with the PDO content of around 42 wt% was used to blend with prescribed amounts of silk fibroin (SF) to build porous single-lumen conduits that are intended to be used for long-gap peripheral nerve repair. Some genipin-crosslinked CH-PDO/SF conduits were endowed with an average porosity of around 60% in their porous wall, and with changed pore-sizes varying from around 10 to ca. 70 MUm using optimized processing conditions. After being degraded in a PBS medium containing a certain amount of lysozyme for various periods up to 8 weeks, some optimal CH-PDO/SF conduits were able to retain their compressive load and deformation recovery at around 59 N/m and 73% in wet state, respectively. In addition, the achieved CH-PDO/SF conduits allowed the permeation of nutritional molecules with various molecular weights while showing a certain ability to prevent cells from infiltrating through the conduit wall. Cell culture confirmed that the optimized CH-PDO/SF conduits were able well supported the growth of rat glioma C6 cells. These results suggest that presently developed CH-PDO/SF conduits have promising potential for long-gap peripheral nerve repair. PMID- 26143353 TI - Numerical simulation of the fracture process in ceramic FPD frameworks caused by oblique loading. AB - Using a newly developed three-dimensional (3D) numerical modeling code, an analysis was performed of the fracture behavior in a three-unit ceramic-based fixed partial denture (FPD) framework subjected to oblique loading. All the materials in the study were treated heterogeneously; Weibull's distribution law was applied to the description of the heterogeneity. The Mohr-Coulomb failure criterion with tensile strength cut-off was utilized in judging whether the material was in an elastic or failed state. The simulated loading area was placed either on the buccal or the lingual cusp of a premolar-shaped pontic with the loading direction at 30 degrees , 45 degrees , 60 degrees , 75 degrees or 90 degrees angles to the occlusal surface. The stress distribution, fracture initiation and propagation in the framework during the loading and fracture process were analyzed. This numerical simulation allowed the cause of the framework fracture to be identified as tensile stress failure. The decisive fracture was initiated in the gingival embrasure of the pontic, regardless of whether the buccal or lingual cusp of the pontic was loaded. The stress distribution and fracture propagation process of the framework could be followed step by step from beginning to end. The bearing capacity and the rigidity of the framework vary with the loading position and direction. The framework loaded with 90 degrees towards the occlusal surface has the highest bearing capacity and the greatest rigidity. The framework loaded with 30 degrees towards the occlusal surface has the least rigidity indicating that oblique loading has a major impact on the fracture of ceramic frameworks. PMID- 26143354 TI - Implication of B lymphocytes in the pathogenesis of ANCA-associated vasculitides. AB - ANCA-associated vasculitis (AAV) is a subgroup of vasculitides characterized by the detection of anti-neutrophil cytoplasm antibodies (ANCA). Until recently, the pathogenesis of AAV mainly involved neutrophils, T cells, and ANCA. Importantly, data were recently published supporting B-cell implication in this setting. Thus, the identification of activated B lymphocytes in granulomatous lesions and the efficacy of B-cell depletion using rituximab in the treatment of patients with AAV changed our mind. However, the impact of B lymphocytes on disease activity and its specific role in the pathogenesis of AAV remains unclear, at least in part as the consequence of the limited number of patients investigated and the restricted number of studies investigating B-cell subsets. Perturbations of B cell homeostasis have been identified in AAV with increased expression of CD38 and decreased expression of CD5 in active phase, contrasting with increased expression of CD25 and CD86 in remission state. Although decreased secretion of interleukin (IL)-10 has also been reported during disease flares, these data remain controversial and the cytokines secretion profile of B-cells needs to be further investigated. Herein, we summarize recent advances in the understanding of the implications of B-cells in the field of AAV and propose new fields of investigation for a better understanding of B lymphocytes in the pathogenesis of AAV. PMID- 26143355 TI - Application of bimodal distribution to the detection of changes in uranium concentration in drinking water collected by random daytime sampling method from a large water supply zone. AB - The random daytime (RDT) sampling method was used for the first time in the assessment of average weekly exposure to uranium through drinking water in a large water supply zone. Data set of uranium concentrations determined in 106 RDT samples collected in three runs from the water supply zone in Wroclaw (Poland), cannot be simply described by normal or log-normal distributions. Therefore, a numerical method designed for the detection and calculation of bimodal distribution was applied. The extracted two distributions containing data from the summer season of 2011 and the winter season of 2012 (nI=72) and from the summer season of 2013 (nII=34) allowed to estimate means of U concentrations in drinking water: 0.947 MUg/L and 1.23 MUg/L, respectively. As the removal efficiency of uranium during applied treatment process is negligible, the effect of increase in uranium concentration can be explained by higher U concentration in the surface-infiltration water used for the production of drinking water. During the summer season of 2013, heavy rains were observed in Lower Silesia region, causing floods over the territory of the entire region. Fluctuations in uranium concentrations in surface-infiltration water can be attributed to releases of uranium from specific sources - migration from phosphate fertilizers and leaching from mineral deposits. Thus, exposure to uranium through drinking water may increase during extreme rainfall events. The average chronic weekly intakes of uranium through drinking water, estimated on the basis of central values of the extracted normal distributions, accounted for 3.2% and 4.1% of tolerable weekly intake. PMID- 26143356 TI - AGS3 is involved in TNF-alpha medicated osteogenic differentiation of human dental pulp stem cells. AB - Dental pulp stem cells (DPSCs) are multipotent adult stem cells capable of differentiating along the osteoblast, adipocyte, and chondrocyte lineages. Regulating differentiation of DPSCs may be a useful tool for regenerative medicine and cell-based therapy in oral diseases. Multisignaling pathways are involved in osteogenic differentiation of DPSCs. Recent studies show that cAMP/PKA/CREB signaling could stimulate the expression of genes such as bone morphogenic proteins 2 (BMP2), inhibitor of DNA binding 2 (ID2), bone sialoprotein, osteocalcin, and type XXIV collagen, which have been implicated in osteogenesis and bone formation. Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, plays an important role in regulating the phosphorylation of cyclic AMP response element-binding protein (p-CREB). However, the involvement of AGS3 in osteogenic differentiation of DPSCs has not been explored. Our data indicated that increased expression of AGS3 would inhibit osteogenic differentiation of DPSCs exposed to inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) via cAMP/PKA/CREB signaling. The negative role of AGS3 in osteogenic differentiation was further confirmed by knocking down and over expression of AGS3. Our findings may provide clinical implications for osteoporosis. PMID- 26143357 TI - Culturally and linguistically diverse healthcare students' experiences of learning in a clinical environment: A systematic review of qualitative studies. AB - CONTEXT: Learning in the clinical environment of healthcare students plays a significant part in higher education. The greatest challenges for culturally and linguistically diverse healthcare students were found in clinical placements, where differences in language and culture have been shown to cause learning obstacles for students. There has been no systematic review conducted to examine culturally and linguistically diverse healthcare students' experiences of their learning in the clinical environment. OBJECTIVE: This systematic review aims to identify culturally and linguistically diverse healthcare students' experiences of learning in a clinical environment. METHODS: The search strategy followed the guidelines of the Centre of Reviews and Dissemination. The original studies were identified from seven databases (CINAHL, Medline Ovid, Scopus, Web of Science, Academic Search Premiere, Eric and Cochrane Library) for the period 2000-2014. Two researchers selected studies based on titles, abstracts and full texts using inclusion criteria and assessed the quality of studies independently. Twelve original studies were chosen for the review. RESULTS: The culturally and linguistically diverse healthcare students' learning experiences were divided into three influential aspects of learning in a clinical environment: experiences with implementation processes and provision; experiences with peers and mentors; and experiences with university support and instructions. The main findings indicate that culturally and linguistically diverse healthcare students embarking on clinical placements initially find integration stressful. Implementing the process of learning in a clinical environment requires additional time, well prepared pedagogical orientation, prior cultural and language education, and support for students and clinical staff. Barriers to learning by culturally and linguistically diverse healthcare students were not being recognized and individuals were not considered motivated; learners experienced the strain of being different, and faced language difficulties. Clinical staff attitudes influenced students' clinical learning experiences and outcomes. CONCLUSION: Additional education in culture and language for students and clinical staff is considered essential to improve the clinical learning experiences of culturally and linguistically diverse healthcare students. Further studies of culturally and linguistically diverse healthcare students' learning experiences in the clinical environment need to be conducted in order to examine influential aspects on the clinical learning found in the review. PMID- 26143358 TI - The association between breastfeeding, the stress response, inflammation, and postpartum depression during the postpartum period: Prospective cohort study. AB - BACKGROUND: Research suggests that exclusive breastfeeding may have a stress protective role in postpartum depression; however, less is known about the underlying mechanisms by which this protection may occur or whether the protective relationship holds for women who mix breast and bottle feeding. OBJECTIVES: To examine patterns of the stress response, inflammation, and depressive symptoms among women predominantly breastfeeding or bottle feeding their infants at 6 months postpartum. DESIGN: A part of a larger longitudinal study across 6 months postpartum investigating the psychoneuroimmunology (PNI) of postpartum depression. SETTING: Prenatal clinics and community. PARTICIPANTS: One hundred nineteen postpartum women who met inclusion/exclusion criteria and followed up from the prenatal period to postpartum 6 months. METHODS: Data were collected during seven home visits occurring during the 3rd trimester (weeks 32 36) and on postpartum days 7 and 14, months 1, 2, 3, and 6. Women completed stress and depression surveys and provided blood for pro- (IL-1beta, IL-6, IL-8, TNF-a, IFN-gamma) and anti-inflammatory (IL-10) cytokines, and collected saliva for diurnal cortisol. RESULTS: Self-report of predominant breastfeeding during 6 months postpartum ranged from 91.9% at day 7 to 70.6% at month 6 postpartum. There were no associations between the pattern of feeding and depressive symptoms. Biological differences, however, existed between the groups, with levels of salivary cortisol at 8 AM and 8:30 AM at month 6 higher and levels of IL-6 at month 6 lower in women who primarily breastfed compared to those who primarily bottle fed their infants after controlling for confounding variables. CONCLUSIONS: Breastfeeding was not related to postpartum depression however differences in stress and inflammatory markers are apparent at month 6 postpartum. PMID- 26143359 TI - Abundance and Relative Distribution of Frankia Host Infection Groups Under Actinorhizal Alnus glutinosa and Non-actinorhizal Betula nigra Trees. AB - Quantitative polymerase chain reaction (qPCR) was used to assess the abundance and relative distribution of host infection groups of the root-nodule forming, nitrogen-fixing actinomycete Frankia in four soils with similar physicochemical characteristics, two of which were vegetated with a host plant, Alnus glutinosa, and two with a non-host plant, Betula nigra. Analyses of DAPI-stained cells at three locations, i.e., at a distance of less than 1 m (near stem), 2.5 m (middle crown), and 3-5 m (crown edge) from the stems of both tree species revealed no statistically significant differences in abundance. Frankiae generally accounted for 0.01 to 0.04 % of these cells, with values between 4 and 36 * 10(5) cells (g soil)(-1). In three out of four soils, abundance of frankiae was significantly higher at locations "near stem" and/or "middle crown" compared to "crown edge," while numbers at these locations were not different in the fourth soil. Frankiae of the Alnus host infection group were dominant in all samples accounting for about 75 % and more of the cells, with no obvious differences with distance to stem. In three of the soils, all of these cells were represented by strain Ag45/Mut15. In the fourth soil that was vegetated with older A. glutinosa trees, about half of these cells belonged to a different subgroup represented by strain ArI3. In all soils, the remaining cells belonged to the Elaeagnus host infection group represented by strain EAN1pec. Casuarina-infective frankiae were not found. Abundance and relative distribution of Frankia host infection groups were similar in soils under the host plant A. glutinosa and the non-host plant B. nigra. Results did thus not reveal any specific effects of plant species on soil Frankia populations. PMID- 26143361 TI - Isolation and characterization of mesenchymal stem cells from the yolk sacs of bovine embryos. AB - The yolk sac (YS) represents a promising source of stem cells for research because of the hematopoietic and mesenchymal cell niches that are present in this structure during the development of the embryo. In this study, we report on the isolation and characterization of YS tissue and mesenchymal stem cells (MSCs) derived from bovine YSs. Our results show that the YS is macroscopically located in the exocoelomic cavity in the ventral portion of the embryo and consists of a transparent membrane formed by a central sac-like portion and two ventrally elongated projections. Immunohistochemistry analyses were positive for OCT4, CD90, CD105, and CD44 markers in the YS of both gestational age groups. The MSCs of bovine YS were isolated using enzymatic digestion and were grown in vitro for at least 11 passages to verify their capacity to proliferate. These cells were also subjected to immunophenotypic characterization that revealed the presence of CD90, CD105, and CD79 and the absence of CD45, CD44, and CD79, which are positive and negative markers of MSCs, respectively. To prove their multipotency, the cells were induced to differentiate into three cell types, chondrocytes, osteoblasts, and adipocytes, which were stained with tissue-specific dyes (chondrogenic: Alcian Blue, osteogenic: Alizarin Red, and adipogenic: Oil Red O) to confirm differentiation. Gene expression analyses showed no differences in the patterns of gene expression between the groups or passages tested, with the exception of the expression of SOX2, which was slightly different in the G1P3 group compared to the other groups. Our results suggest that YS tissue from bovines can be used as a source of MSCs, which makes YS tissue-derived cells an interesting option for cell therapy and regenerative medicine. PMID- 26143360 TI - Pig oocyte activation using a Zn2+ chelator, TPEN. AB - Artificial oocyte activation is a critical step during SCNT. Most current activation protocols focus on inducing an increase in the intracellular free Ca(2+) concentration of the oocyte. Here, we have used a zinc chelator, TPEN, to enhance the efficiency of oocyte activation during SCNT. TPEN treatment of matured pig oocytes resulted in the reduction of available Zn(2+) in pig oocytes; however, the cytosolic Ca(2+) concentration in the oocytes was not affected by the TPEN treatment. When various concentrations (100-250 MUM) and incubation durations (45 minutes-2.5 hours) of TPEN were used to activate oocytes, the efficiency of oocyte activation was not different from conventional activation methods. When oocytes that were activated by conventional activation methods were incubated with a lower concentration of TPEN (5-10 MUM), a significant increase in embryos developing to the blastocyst stage was observed. In addition, when oocytes receiving a small Ca(2+) stimulus were further activated by higher concentration of TPEN (100-200 MUM), a significant increase in the frequency of blastocyst formation was observed, compared to a conventional activation method. This result indicated that TPEN can be a main reagent in oocyte activation. No increase in the cytosolic Ca(2+) level was detected when oocytes were exposed to various concentrations of TPEN, indicating the ability of TPEN to induce oocyte activation is independent of an intracellular Ca(2+) increase. We were able to produce clones through SCNT by using the TPEN-assisted activation procedure, and the piglets produced through the process did not show any signs of abnormality. In this study, we have developed an efficient way to use TPEN to increase the developmental potential of cloned embryos. PMID- 26143362 TI - eCG concentrations, luteal structures, return to cyclicity, and postabortion fertility in embryo transfer recipient mares. AB - The present study characterizes the relationship between the levels of eCG, ovarian morphology, resumption of cyclicity, and fertility in postaborted embryo transfer recipient mares. A total of 32 pregnant recipient mares carrying a male fetus were aborted at approximately 65 days of gestation by single transcervical administration of cloprostenol. In addition, 25 gestation age-matched mares were used as nonaborted controls. The concentration of progesterone, but not of eCG, differed significantly between controls and aborted mares 48 hours after abortion. Of treated mares, 84.4% (27 of 32) expelled the fetus within 48 hours of treatment. The eCG concentration and the number of supplementary luteal structures were lower in mares aborted in November (equivalent to May in Northern Hemisphere) than in January. A total of 6.2%, 37.5%, and 56.2% of the mares entered anestrus, ovulated normally, and had 1 to 2 consecutive anovulatory cycles, respectively. The mean interval from abortion to the first ovulation was 28.5 +/- 3.3 days (range, 5-65 days). The correlation between the levels of eCG at abortion and the interval to the first ovulation was poor (r = 0.38; P = 0.03). Of aborted mares, 90% (18 of 20) were reused and became pregnant after embryo transfer at a mean of 57.6 +/- 4.4 days after abortion (range, 19-103 days) and eCG concentration of 0.9 +/- 0.3 IU/mL (range, 0.1-3.6 IU/mL). In conclusion, the levels of eCG at the time of abortion were extremely variable and did not correlate well with the number of luteal structures or the interval from abortion to the first ovulation. PMID- 26143363 TI - The effects of colours, shapes and boundaries of landscapes on perception, emotion and mentalising processes promoting health and well-being. AB - Place has a special characteristic - a physical visual shape - that operates as an intensive visual idea. Drawing from the 'therapeutic landscape' concept (Gesler, 1992), this study focuses on the clients in a psychiatric clinic in Switzerland and how they experience place through a psychotherapeutic painting and autobiographical narration process. Based on an inductive qualitative approach, the narratives are structured in an open coding process orientated toward 'blue' and 'green' space, based on the space and place discourse of Relph (1976). Two dimensions of Relph's (1976) 'perceptual and existential' space exist in the narratives of the clients: firstly an individual dimension associated with perception and feelings, with meaning and symbolism, as well as with health and wellbeing; and secondly, a place-landscape dimension with diversification of colours, shapes and borders. In the interaction between individuals and place and landscape, a perceptional, emotional, mentalising process emerges that contributes meaningfully to health and well-being. PMID- 26143364 TI - Differential expression of vascular endothelial growth factor angiogenic factors in different endometrial compartments in women who have an elevated progesterone level before oocyte retrieval, during in vitro fertilization-embryo transfer treatment. AB - OBJECTIVE: To investigate the relationship between endometrial expressions of angiogenic factors around the time of embryo implantation and P level before oocyte retrieval during IVF-ET treatment. DESIGN: Retrospective study. SETTING: University Assisted Reproductive Unit. PATIENT(S): Forty patients were recruited, 20 women with an elevated P level, and 20 women with a normal P level, into cancelled embryo transfer (ET) cycles. INTERVENTION(S): Endometrial biopsy samples were obtained from women who had an elevated or normal P level 7 days after human chorionic gonadotropin administration. The protein expression levels of VEGF-A, VEGF-C, and PLGF were examined using immunohistochemistry. MAIN OUTCOME MEASURE(S): A semiquantitative analysis was performed using histochemical score analysis of staining intensity in the luminal epithelium, glandular epithelium, and stroma, separately. RESULT(S): Luminal epithelial expression of vascular endothelial growth factor (VEGF)-A, VEGF-C, and PLGF did not significantly differ in women with elevated or normal P levels before oocyte retrieval. Glandular epithelial expression of VEGF-A, VEGF-C, and PLGF was higher in women with elevated P levels, compared with those with normal P levels. A significantly higher stromal expression of VEGF-A and PLGF was found in women with elevated P levels. CONCLUSION(S): A high P level before oocyte retrieval was associated with expression of VEGF angiogenic factors in glandular epithelium and stromal compartment around the time of embryo implantation. Our findings suggest that the lower implantation rates observed in this group of women may relate to decreased endometrial receptivity arising from altered expression of angiogenic factors. PMID- 26143365 TI - Spermatozoa from patients with seminal alterations exhibit a differential micro ribonucleic acid profile. AB - OBJECTIVE: To compare the microRNA (miRNA) expression profile in spermatozoa from three infertile populations vs. a group of fertile men. DESIGN: Evaluation of the expression level of 736 miRNAs in human spermatozoa using TaqMan quantitative reverse transcription-polymerase chain reaction. SETTING: University research facility. PATIENT(S): Semen samples with a single seminal alteration were collected from infertile individuals: asthenozoospermic (n = 10), teratozoospermic (n = 10), and oligozoospermic (n = 10). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Correlation of the expression level of each miRNA with seminal parameters, age, and chromosome instability; clustering of the individuals according to their miRNA expression profiles and influence of the seminogram, age, chromosome instability, and assisted reproductive technology outcome in the clustering; analysis of the differentially expressed miRNAs (DE miRNAs) in each infertile population; genome annotation of these DE-miRNAs; and ontological analysis of their predicted targets. RESULT(S): The hsa-miR-34b-3p correlated with age, the hsa-miR-629-3p with sperm motility, and the hsa-miR-335 5p, hsa-miR-885-5p, and hsa-miR-152-3p with sperm concentration. The individuals clustered into two groups, and only the seminogram was differentially distributed. We identified 32 DE-miRNAs in the asthenozoospermic group, 19 in the teratozoospermic group, and 18 in the oligozoospermic group. The up-regulated miRNAs presented an enriched localization in introns, affecting relevant genes for spermatogenesis. The predicted targets of the DE-miRNAs contained critical genes associated to infertility, and their ontological analysis revealed significantly associated functions related to the seminal alterations of each group. CONCLUSION(S): Spermatozoa from patients with seminal alterations exhibit a differential miRNA profile. This provides new evidence that miRNAs have an essential role in spermatogenesis, contributing to the mechanisms involved in human fertility. PMID- 26143367 TI - Development and evaluation of gastroretentive raft forming systems incorporating curcumin-Eudragit(r) EPO solid dispersions for gastric ulcer treatment. AB - Novel raft forming systems incorporating curcumin-Eudragit(r) EPO solid dispersions were developed to prolong the gastric residence time and provide for a controlled release therapy of curcumin to treat gastric ulcers. The solid dispersions of curcumin with Eudragit(r) EPO were prepared by the solvent evaporation method at various ratios to improve the solubility and the dissolution of curcumin. The optimum weight ratio of 1:5 for curcumin to Eudragit(r) EPO was used to incorporate into the raft forming systems. The raft forming formulations were composed of curcumin-Eudragit(r) EPO solid dispersions, sodium alginate as a gelling polymer and calcium carbonate for generating divalent Ca(2+) ions and carbon dioxide to form a floating raft. All formulations formed a gelled raft in 1min and sustained buoyancy on the 0.1N hydrochloric acid (pH 1.2) surface with a 60-85% release of curcumin within 8h. The curative effect on the acetic acid-induced chronic gastric ulcer in rats was determined. The curcumin raft forming formulations at 40mg/kg once daily showed a superior curative effect on the gastric ulcer in terms of the ulcer index and healing index than the standard antisecretory agent: lansoprazole (1mg/kg, twice daily) and a curcumin suspension (40mg/kg, twice daily). These studies demonstrated that the new raft forming systems containing curcumin solid dispersions are promising carriers for a stomach-specific delivery of poorly soluble lipophilic compounds. PMID- 26143366 TI - Sleep Quality Among Latino Farmworkers in North Carolina: Examination of the Job Control-Demand-Support Model. AB - Sleep problems are associated with physical and mental health disorders and place individuals at an increased risk of workplace injuries. The demand-control support model posits that job demands and the capacity to control work processes influence workers' level of distress, thereby affecting their physical and mental health; supervisor support can buffer the negative effect of high demands and low control. Data on the sleep quality and the organization of work of Latino men were collected in agricultural areas in North Carolina in 2012. 147 Mexican-born farmworkers ages 30 and older, most of whom had H-2A visas, provided information about sleep quality and organization of work. Most (83 %) farmworkers reported good sleep quality. The association between working more than 40 h per week and reporting poor sleep quality approached statistical significance. Additional research is needed to understand whether job demands, job control, and social support affect farmworkers' sleep quality. PMID- 26143368 TI - Development of highly stabilized curcumin nanoparticles by flash nanoprecipitation and lyophilization. AB - The influence of critical operating parameters on the Flash Nanoprecipitation (FNP) and resulting material properties of curcumin (CUR) nanoparticles has been evaluated using a confined impinging jets-with-dilution mixer (CIJ-D-M). It has been shown that the mixing rate, molecular weight of polymeric stabilizer (i.e., polyethylene glycol-b-poly(dl-lactide) di-block copolymer; PEG-PLA) and drug-to copolymer mass ratio all exert a significant impact on the particle size and stability of the generated nanosuspensions. The attainable mean particle size and span of the nanoparticles through optimization of these process parameters were approximately 70nm and 0.85 respectively. However, the optimized nanosuspension was only stable for about two hours after preparation. Co-formulation with polyvinylpyrrolidone (PVP) substantially extended the product lifespan to 5days at ambient conditions and two weeks at 4 degrees C. Results from zeta potential measurement and X-ray photoelectron spectroscopy (XPS) suggested that the enhanced stability is probably due to the formation of an additional protective barrier by PVP around the particle surface, thereby suppressing the dissociation of PEG-PLA from the particles and preventing CUR leakage from inside. Long-term storage stability (>1year) could be achieved by lyophilization of the optimized nanosuspension with Kleptose (hydroxypropyl-beta-cyclodextrin), which was shown to be the only effective lyoprotectant among all the ones tested for the CUR nanoparticles. At an optimal concentration of Kleptose (1.25% w/v), the redispersibility (Sf/Si; ratio of the final and initial particle sizes) and encapsulation efficiency of lyophilized CUR nanoparticles were about 1.22% and 94%, respectively. PMID- 26143369 TI - The influence of polymer content on early gel-layer formation in HPMC matrices: The use of CLSM visualisation to identify the percolation threshold. AB - Percolation theory has been used for several years in the design of HPMC hydrophilic matrices. This theory predicts that a minimum threshold content of polymer is required to provide extended release of drug, and that matrices with a lower polymer content will exhibit more rapid drug release as a result of percolation pathways facilitating the faster penetration of the aqueous medium. At present, percolation thresholds in HPMC matrices have been estimated solely through the mathematical modelling of dissolution data. This paper examines whether they can be also identified in a novel way: through the use of confocal laser scanning fluorescence microscopy (CLSM) to observe the morphology of the emerging gel layer during the initial period of polymer hydration and early gel formation at the matrix surface. In this study, matrices have been prepared with a polymer content of 5-30% w/w HPMC 2208 (Methocel K4M), with a mix of other excipients (a soluble drug (caffeine), lactose, microcrystalline cellulose and magnesium stearate) to provide a typical industrially realistic formulation. Dissolution studies, undertaken in water using USP apparatus 2 (paddle) at 50rpm, provided data for the calculation of the percolation threshold through relating dissolution kinetic parameters to the excipient volumetric fraction of the dry matrix. The HPMC percolation threshold estimated this way was found to be 12.8% v/v, which was equivalent to a matrix polymer content of 11.5% w/w. The pattern of polymer hydration and gel layer growth during early gel layer formation was examined by confocal laser scanning fluorescence microscopy (CLSM). Clear differences in gel layer formation were observed. At polymer contents above the estimated threshold a continuous gel layer was formed within 15min, whereas matrices with polymer contents below the threshold were characterised by irregular gel layer formation with little evidence of HPMC particle coalescence. According to percolation theory, this implies that a continuous cluster of HPMC particles was not formed. The images provide the first direct evidence of how the percolation threshold may be related to the success or failure of early gel layer development in HPMC matrices. It also shows how extended release characteristics are founded on the successful coalescence of hydrated polymer particles to form a continuous coherent diffusion barrier, which can then inhibit further percolation of the hydration medium. The correlation between percolation thresholds estimated from dissolution and imaging techniques suggests that confocal imaging may provide a more rapid method for estimating the percolation thresholds, facilitating the rational design of HPMC extended release matrices at lower polymer contents with minimal risk of dose dumping. PMID- 26143370 TI - Inhibitory effect of UvrD and DinG on the replication of ColE1-derived plasmids in Escherichia coli. AB - CspA has been identified as a major cold-shock protein in Escherichia coli. CspA binds to RNAs which are abnormally folded at low temperature and then acts as an RNA chaperone unfolding those RNAs. The dramatic expression of cspA at low temperature is contributed by posttranscriptional stability and robust translatability. Interestingly, when cspA mRNA encoding a premature nonsense codon was overexpressed at low temperature, cell growth was completely inhibited. This phenotype was termed LACE (the low temperature-dependent antibiotic effect of truncated cspA expression), and this lethality resulted from exclusive stalling of most ribosomes on mutant cspA mRNAs. In a previous study, we demonstrated that overexpression of the ATP-dependent DNA helicases, UvrD and DinG, suppressed the lethality and ribosome stalling caused by mutant cspA mRNA. In the present study, we attempted to elucidate how these two DNA helicases help recover normal growth under LACE condition. Interestingly, we found that UvrD and DinG appeared to have an ability to down-regulate the replication of pUC-based high copy plasmid. In plasmid copy number tests, the amount of pUC-based plasmid encoding mutant cspA was reduced by 3-10-fold when either UvrD or DinG was expressed. Through a beta-galactosidase activity assay, we also confirmed that expression of the lacZalpha gene inserted into the pUC-based plasmid was significantly reduced due to down-regulation of plasmid replication. Our findings imply that UvrD and DinG, known as non-replicative helicases, play a novel role in the regulation of ColE1-like plasmid replication. PMID- 26143371 TI - The Nachlass (estate) of Heinrich von Eggeling (1869-1954), long-time secretary of the Anatomische Gesellschaft. AB - Heinrich von Eggeling (1869-1954), professor of anatomy in Breslau from 1922, was secretary of the Anatomische Gesellschaft (AG) from 1919 until 1949 and also editor of the Anatomischer Anzeiger, today's Annals of Anatomy. His "Wissenschaftlicher Nachlass [scientific estate]" could recently be located in private hands and has now been made available at the archive of the AG held by the current secretary. It consists of 45 folders, mainly containing von Eggeling's national and international correspondence from 1919 to 1953. It thus covers the times of the Weimar republic and of the "Third Reich" as well as the post-war period, when the AG had been officially closed down by the Allied Control Council and was eventually re-founded in 1949. Von Eggeling preserved this material despite war destruction of his Berlin home, where he lived after his retirement in 1935, and his cramped post-war confines in a small town near Hannover. The estate also includes autobiographical manuscripts of von Eggeling and some material from his predecessor, the first secretary of the AG since 1886, Karl von Bardeleben (1849-1918). There is evidence that the correspondence is not complete, even if there are no significant time gaps. The contents suggest that letters deemed insignificant, like fee reminders or editorial decisions, were discarded at some point, but it remains unclear by whom. This estate fills a significant gap in the historical material related to the AG and will be an important source for any future historical investigation regarding the society. PMID- 26143372 TI - Single cell imaging reveals that the motility regulator speract induces a flagellar alkalinization that precedes and is independent of Ca2+ influx in sea urchin spermatozoa. AB - Speract, a peptide from the egg jelly coat of certain sea urchin species, modulates sperm motility through a signaling pathway involving several ionic fluxes leading to pHi and [Ca2+]i increases. [Ca2+]i oscillations in the flagellum regulate its beating pattern modulating sperm swimming. Recent evidence showed the importance of pHi in controlling Ca2+ influx and chemotaxis. However, spatio-temporal characterization of the flagellar pHi increase triggered by speract, and its correlation to that of [Ca2+]i is lacking. Here, we show for the first time in single sea urchin spermatozoa that the speract-induced flagellar pHi increase precedes and is independent of [Ca2+]i increase. Our results support a leading role of pHi in modulating the Ca2+ signals that govern sperm swimming. PMID- 26143373 TI - Double stranded promoter region of BRAF undergoes to structural rearrangement in nearly physiological conditions. AB - The folding of oncogene promoters into non-canonical DNA secondary structures is considered a strategy to control gene expression. Herein, we focused on a 30 bases sequence located upstream of the transcription start site of BRAF (Braf 176) that contains 80% of guanines. We analyzed the structural behavior of the G- and C-rich strands. By the use of spectroscopic and electrophoretic techniques we confirmed that they actually fold into a predominant antiparallel G-quadruplex and into an i-motif, respectively, and that they can coexist at nearly physiological conditions. Finally, the influence of several factors (KCl, pH, PEG200) on the conversion of the double stranded form of the oncogene promoter into the two above mentioned non-canonical structures has been explored. PMID- 26143374 TI - Identification of the receptor tyrosine kinases (RTKs)-oriented functional targets of miR-206 by an antibody-based protein array. AB - This study demonstrated the feasibility and benefit of an antibody-based experimental approach to identify microRNA functional targets from hundreds of predicted genes using miR-206 as an example. Using a receptor tyrosine kinase (RTK) antibody array, we identified 7 phosphorylated RTKs that were significantly differentially regulated after miR-206-mimic transfection. We then focused on MET, the most varied RTK, and bioinformatically constructed a MET-centred network using computationally predicted miR-206 targets. Within this network, we analyzed two validated targets, PAX3 and SNX2, and one candidate target, EIF4E, may account for the inhibitory effect of miR-206 on MET phosphorylation. Luciferase and Western-blot assays indicated that EIF4E was a direct target of miR-206. This concept may also be applicable for other microRNAs and other antibody array platforms. PMID- 26143375 TI - Review and Hypothesis. New insights into the reaction mechanism of transhydrogenase: Swivelling the dIII component may gate the proton channel. AB - The membrane protein transhydrogenase in animal mitochondria and bacteria couples reduction of NADP+ by NADH to proton translocation. Recent X-ray data on Thermus thermophilus transhydrogenase indicate a significant difference in the orientations of the two dIII components of the enzyme dimer (Leung et al., 2015). The character of the orientation change, and a review of information on the kinetics and thermodynamics of transhydrogenase, indicate that dIII swivelling might assist in the control of proton gating by the redox state of bound NADP+/NADPH during enzyme turnover. PMID- 26143376 TI - In vitro substrate specificities of 3'-5' polymerases correlate with biological outcomes of tRNA 5'-editing reactions. AB - Protozoan mitochondrial tRNAs (mt-tRNAs) are repaired by a process known as 5' editing. Mt-tRNA sequencing revealed organism-specific patterns of editing G-U base pairs, wherein some species remove G-U base pairs during 5'-editing, while others retain G-U pairs in the edited tRNA. We tested whether 3'-5' polymerases that catalyze the repair step of 5'-editing exhibit organism-specific preferences that explain the treatment of G-U base pairs. Biochemical and kinetic approaches revealed that a 3'-5' polymerase from Acanthamoeba castellanii tolerates G-U wobble pairs in editing substrates much more readily than several other enzymes, consistent with its biological pattern of editing. PMID- 26143377 TI - Preferential awareness of protofacial stimuli in autism. AB - It has been suggested that a subcortically mediated, innate sensitivity to protofacial stimuli leads to specialized face processing and to the development of the social brain. A dysfunction of this face-processing pathway has been associated with atypical social development in individuals with autism spectrum disorder (ASD). This study investigated whether individuals with ASD exhibit primary sensitivity to monochrome protoface stimuli using continuous flash suppression (CFS). Under CFS, visual stimuli are suppressed from awareness, and cortical processing is strongly reduced while subcortical regions continue to respond to invisible stimuli. We found that both adolescents with ASD and typically developing adolescents showed preferential detection of upright protoface stimuli under CFS but not in a non-CFS control condition. These results challenge the notion that a primitive sensitivity to protoface stimuli is essential for typical social development. Rather, our findings suggest such sensitivity is not a sufficient condition for typical social development and that the presence of other complementary factors is necessary for the development of the social brain. PMID- 26143378 TI - Characterization of lipid droplets in steroidogenic MLTC-1 Leydig cells: Protein profiles and the morphological change induced by hormone stimulation. AB - Lipid droplets (LDs) are functional subcellular organelles involved in multiple intracellular processes. LDs are found in nearly all types of eukaryotic cells, but their properties are highly variable in different types of tissues. Steroidogenic cells synthesize steroid hormones de novo from the cholesterol deposited in cytosolic LDs. However, the roles of LD proteins in steroidogenesis under pituitary hormone stimulation have not been well elucidated. The protein profile of isolated LDs from the mouse Leydig tumor cell line MLTC-1 was distinct from that of hepatic cells or macrophages. By proteomic analysis of the components using mass spectrometry, two enzymes for steroidogenesis, 3beta hydroxysteroid dehydrogenase type 1 (3betaHSD1) and 17 beta-hydroxysteroid dehydrogenase type 11 (17betaHSD11), were identified in two strong bands in the LD fractions. The LD fraction of MLTC-1 cells also included CYP11A1 and CYP17, suggesting that the LDs contain all the enzymes needed for testosterone synthesis. The steroidogenesis in Leydig cells is activated by luteinizing hormone through a PKA-dependent pathway. Stimulation of MLTC-1 cells with luteinizing hormone or 8-bromo-cAMP caused drastic changes in the morphology of the LDs in the MLTC-1 cells. Upon stimulation, large perinuclear LDs are turned into much smaller LDs and dispersed throughout the cytosol. These results raise the possibility that LDs are involved in a regulatory pathway of steroidogenesis, not just by serving as a storage depot for cholesterol esters, but also by providing enzymes and generating sites for enzymatic activity. PMID- 26143379 TI - Short-chain polyisoprenoids in the yeast Saccharomyces cerevisiae - New companions of the old guys. AB - Dolichols are, among others, obligatory cofactors of protein glycosylation in eukaryotic cells. It is well known that yeast cells accumulate a family of dolichols with Dol-15/16 dominating while upon certain physiological conditions a second family with Dol-21 dominating is noted. In this report we identified the presence of additional short-chain length polyprenols - all-trans Pren-7 in three yeast strains (SS328, BY4741 and L5366), Pren-7 was accompanied by traces of putative Pren-6 and -8. Moreover, in two of these strains a single polyprenol mainly-cis-Pren-11 was synthesized at the stationary phase of growth. Identity of polyprenols was confirmed by HR-HPLC/MS, NMR and metabolic labeling. Additionally, simvastatin inhibited their biosynthesis. PMID- 26143380 TI - Evaluating computational models of cholesterol metabolism. AB - Regulation of cholesterol homeostasis has been studied extensively during the last decades. Many of the metabolic pathways involved have been discovered. Yet important gaps in our knowledge remain. For example, knowledge on intracellular cholesterol traffic and its relation to the regulation of cholesterol synthesis and plasma cholesterol levels is incomplete. One way of addressing the remaining questions is by making use of computational models. Here, we critically evaluate existing computational models of cholesterol metabolism making use of ordinary differential equations and addressed whether they used assumptions and make predictions in line with current knowledge on cholesterol homeostasis. Having studied the results described by the authors, we have also tested their models. This was done primarily by testing the effect of statin treatment in each model. Ten out of eleven models tested have made assumptions in line with current knowledge of cholesterol metabolism. Three out of the ten remaining models made correct predictions, i.e. predicting a decrease in plasma total and LDL cholesterol or increased uptake of LDL upon treatment upon the use of statins. In conclusion, few models on cholesterol metabolism are able to pass a functional test. Apparently most models have not undergone the critical iterative systems biology cycle of validation. We expect modeling of cholesterol metabolism to go through many more model topologies and iterative cycles and welcome the increased understanding of cholesterol metabolism these are likely to bring. PMID- 26143381 TI - Active autophagy but not lipophagy in macrophages with defective lipolysis. AB - During autophagy, autophagosomes fuse with lysosomes to degrade damaged organelles and misfolded proteins. Breakdown products are released into the cytosol and contribute to energy and metabolic building block supply, especially during starvation. Lipophagy has been defined as the autophagy-mediated degradation of lipid droplets (LDs) by lysosomal acid lipase. Adipose triglyceride lipase (ATGL) is the major enzyme catalyzing the initial step of lipolysis by hydrolyzing triglycerides (TGs) in cytosolic LDs. Consequently, most organs and cells, including macrophages, lacking ATGL accumulate TGs, resulting in reduced intracellular free fatty acid concentrations. Macrophages deficient in hormone-sensitive lipase (H0) lack TG accumulation albeit reduced in vitro TG hydrolase activity. We hypothesized that autophagy is activated in lipase deficient macrophages to counteract their energy deficit. We therefore generated mice lacking both ATGL and HSL (A0H0). Macrophages from A0H0 mice showed 73% reduced neutral TG hydrolase activity, resulting in TG-rich LD accumulation. Increased expression of cathepsin B, accumulation of LC3-II, reduced expression of p62 and increased DQ-BSA dequenching suggest intact autophagy and functional lysosomes in A0H0 macrophages. Markedly decreased acid TG hydrolase activity and lipid flux independent of bafilomycin A1 treatment, however, argue against effective lysosomal degradation of LDs in A0H0 macrophages. We conclude that autophagy of proteins and cell organelles but not of LDs is active as a compensatory mechanism to circumvent and balance the reduced availability of energy substrates in A0H0 macrophages. PMID- 26143382 TI - Parents' Role in Adolescent Depression Care: Primary Care Provider Perspectives. AB - OBJECTIVE: To understand how primary care providers (PCPs) perceive barriers to adolescent depression care to inform strategies to increase treatment engagement. STUDY DESIGN: We conducted semistructured interviews with 15 PCPs recruited from community pediatric offices with access to integrated behavioral health services (ie, low system-level barriers to care) who participated in a larger study on treating adolescent depression. Interviews addressed PCP perceptions of barriers to adolescents' uptake of care for depression. Interviews were audiorecorded, transcribed, and coded for key themes. RESULTS: Although PCPs mentioned several adolescent barriers to care, they thought parents played a critical role in assisting adolescents in accessing mental health services. Important aspects of the parental role in accessing treatment included transportation, financial support, and social support. PCPs perceived that parental unwillingness to accept the depression diagnosis, family dysfunction, and trauma were common barriers. PCPs contrasted this with examples of good family support they believed would enable adolescents to attend follow-up appointments and have a "life coach" at home to help monitor for side effects and watch for increased suicidality when starting antidepressants. CONCLUSIONS: In this PCP population, which had enhanced access to mental health specialists, PCPs primarily reported attitudinal barriers to adolescent depression treatment, focusing mainly on perceived parent barriers. The results of these qualitative interviews provide a framework for understanding PCP perceptions of parental barriers to care, identifying that addressing complex parental barriers to care may be important for future interventions. PMID- 26143383 TI - Sexual Behavior and Contraceptive Use among 18- to 19-Year-Old Adolescent Women by Weight Status: A Longitudinal Analysis. AB - OBJECTIVE: To describe the association between weight status and sexual practices among 18- to 19-year-old women. STUDY DESIGN: We analyzed a population-based longitudinal study of 18- to 19-year-old women residing in a Michigan county at cohort inception. Weekly journal surveys measured sexual practices, including contraceptive behaviors. Outcomes included proportion of weeks with a partner, proportion of weeks with sexual intercourse, number of partners, average length of relationships, proportion of weeks with contraception use, and proportion of weeks where contraception was used consistently. We examined 26,545 journal surveys from 900 women over the first study year. Ordinary least squares regression models for each outcome examined differences by weight status, controlling for sociodemographic characteristics. RESULTS: The mean proportion of weeks in which adolescents reported sexual intercourse was 52%; there was no difference by weight status. Among weeks in which adolescents reported sexual activity, obese adolescents had a lower proportion of weeks where any contraception was used compared with normal weight adolescents (84% vs 91%, P = .011). Among weeks in which adolescents reported sexual activity and contraceptive use, obese adolescents had a lower proportion of weeks with consistent contraceptive use (68% vs 78%, P = .016) and oral contraceptive pill use (27% vs 45%, P = .001) compared with normal weight adolescents. All other relationships by weight status were not statistically significant. CONCLUSIONS: In this longitudinal study, obese adolescent women were less likely to use contraception, and less likely to use it consistently when compared with normal weight peers. Findings suggest obesity may be an important factor associated with adolescent women's sexual behavior. PMID- 26143384 TI - Short-Term Treprostinil Use in Infants with Congenital Diaphragmatic Hernia following Repair. AB - We describe 2 infants with congenital diaphragmatic hernia with severe pulmonary hypertension at 6 weeks. Treprostinil was used with rapid clinical improvement. Repeat cardiac catheterization showed dramatic improvement. Both infants were weaned off the drug, representing the first reports of successful short-term treprostinil use in neonates with congenital diaphragmatic hernia. PMID- 26143385 TI - The promise of treatment as prevention for hepatitis C: Meeting the needs of people who inject drugs? AB - Treatment as prevention (TasP) is a concept common to the HIV sector. In this commentary we draw on the literature addressing HIV and HCV TasP, alongside qualitative HCV research, to critically appraise the promise of TasP for HCV and assess the needs of PWID in the future of HCV care. With the advent of highly effective direct-acting antiviral HCV treatments, TasP is now under consideration for HCV. A growing body of literature documents numerous social structural barriers to HCV treatment access and uptake for PWID, among whom HCV is highly prevalent. Yet these barriers - and suggestions for surmounting them - are rarely included in emergent literature on HCV TasP. Although HCV TasP has important advocacy potential for increasing treatment access among PWID, critical reflection on its implications are warranted. We outline potential limitations of TasP for HCV and the conditions under which it might be optimised. We argue that HCV treatment as a prevention strategy can only be realisable in a context of enhanced harm reduction access, meaningful community engagement, and enabling environment interventions informed by the needs and perspectives of PWID. PMID- 26143386 TI - Management of rotator cuff calcific tendinosis guided by ultrasound elastography. AB - BACKGROUND: Ultrasound (US) elastography can provide information about the hardness of calcification and might help decide treatment strategy. The purpose of this study was to evaluate the hardness of the calcific area within rotator cuffs by US elastography as an aid for the selection of aspiration or fine-needle repeated puncture for the treatment of rotator cuff calcific tendinosis. METHODS: This prospective study included 39 patients (32 males, 7 females; mean age, 52.9 years) who received US elastography and gray-scale ultrasonography before US guided treatment for rotator cuff calcific tendinosis. The morphology of the calcifications was classified as arc, fragmented, nodular, and cystic types. US elastography using virtual touch imaging (acoustic radiation force impulse) technique was performed to examine the calcified region to obtain an elastogram that was graded dark, intermediate, or bright. The hardness of the calcifications were recorded, and graded as hard, sand-like, or fluid-like tactile patterns during the US-guided treatment, and the tactile patterns were compared with the results of US elastography and gray-scale ultrasonography. RESULTS: Though the morphologies of the calcifications were significantly related to the tactile pattern of the needle punctures (p < 0.001), gray-scale US could not accurately demonstrate the hardness of the calcifications. With the aid of elastography, the fluid-like tactile pattern could be predicted well as a nondark pattern by elastography (p < 0.001). CONCLUSION: Ultrasound elastography is a useful modality for evaluation of rotator cuff calcific tendinosis, and as an aid to guide management. If elastography shows the calcified area as a non-dark pattern, then fine-needle aspiration should be performed. PMID- 26143387 TI - The effect of preprocedure anxiety levels on postprocedure pain scores in women undergoing hysterosalpingography. AB - BACKGROUND: Hysterosalpingography (HSG) is an invasive, uncomfortable, and painful procedure. Patients often experience considerable anxiety and stress before the procedure. In this study, we aimed to evaluate the effect of preprocedure anxiety on postprocedure pain scores and clinical outcomes in women undergoing HSG. METHODS: This study was designed as a prospective randomized study. Women undergoing HSG were asked to complete the Beck Anxiety Inventory before the procedure. Patients were classified into two groups according to the anxiety score (Group 1: anxiety score <= 25; n = 84 and Group 2: anxiety score > 25, n = 25). All of the patients were asked to state the severity of their pain during the procedure using a visual analogue scale immediately after the procedure. Then, postprocedure pain scores and clinical features were evaluated. Data analyzed were: age, gravidity, parity, durations of marriage and infertility, body mass index, procedure time, amount of contrast media used, operator sex, history of surgery, educational level, and HSG results. RESULTS: A total of 109 women were enrolled into this prospective study. There was no statistically significant difference between the groups in terms of age, body mass index, durations of marriage and infertility, procedure time, amount of contrast media used, operator sex, history of surgery, educational level, and patency of the one and/or two fallopian tubes (p > 0.05). The median parity and pain scores after the procedure were lower in Group 1 (p < 0.05). There was also a positive correlation between anxiety scores and postprocedure pain scores (r = 0.289, p = 0.002). Receiver operator characteristics curve analysis demonstrated that operator sex was an important risk factor for postprocedure pain in patients with a preprocedure Beck Anxiety Inventory > 25. Logistic regression method demonstrated that higher parity, preprocedure anxiety score > 25, and male operator were risk factors for increased postprocedure visual analogue scale scores. CONCLUSION: According to this study, preprocedure anxiety levels have an effect on postoperative pain scores in women undergoing HSG procedure. Multiparity, male operator, and higher preprocedure anxiety scores also may have an effect on postoperative pain scores. PMID- 26143388 TI - Isolation and characterisation of transport-defective substrate-binding mutants of the tetracycline antiporter TetA(B). AB - The tetracycline antiporter TetA(B) is a member of the Major Facilitator Superfamily which confers tetracycline resistance to cells by coupling the efflux of tetracycline to the influx of protons down their chemical potential gradient. Although it is a medically important transporter, its structure has yet to be determined. One possibility for why this has proven difficult is that the transporter may be conformationally heterogeneous in the purified state. To overcome this, we developed two strategies to rapidly identify TetA(B) mutants that were transport-defective and that could still bind tetracycline. Up to 9 amino acid residues could be deleted from the loop between transmembrane alpha helices 6 and 7 with only a slight decrease in affinity of tetracycline binding as measured by isothermal titration calorimetry, although the mutant was transport-defective. Scanning mutagenesis where all the residues between 2 and 389 were mutated to either valine, alanine or glycine (VAG scan) identified 15 mutants that were significantly impaired in tetracycline transport. Of these mutants, 12 showed no evidence of tetracycline binding by isothermal titration calorimetry performed on the purified transporters. In contrast, the mutants G44V and G346V bound tetracycline 4-5 fold more weakly than TetA(B), with Kds of 28 MUM and 36 MUM, respectively, whereas the mutant R70G bound tetracycline 3-fold more strongly (Kd 2.1 MUM). Systematic mutagenesis is thus an effective strategy for isolating transporter mutants that may be conformationally constrained and which represent attractive targets for crystallisation and structure determination. PMID- 26143389 TI - Developing Primary Intervention Strategies to Prevent Allergic Disease. AB - Allergic diseases are a major cause of morbidity in the developed world, now affecting up to 40 % of the population with no evidence that this is abating. If anything, the prevalence of early onset allergic diseases such as eczema and food allergy appears to be still increasing. This is almost certainly due to the changing modern environment and lifestyle factors, acting to promote immune dysfunction through early perturbations in immune maturation, immune tolerance and regulation. This early propensity to inflammation may also have implications for the rising risk of other inflammatory non-communicable diseases (NCDs) later in life. Identifying risk factors and pathways for preventing early onset immune disease like allergy is likely to have benefits for many aspects of human health, particularly as many NCDs share similar risk factors. This review focuses on recent advances in primary intervention strategies for promoting early immune health and preventing allergic disease, highlighting the current evidence-based guidelines where applicable and areas requiring further investigation. PMID- 26143391 TI - Technological Innovations for High-Throughput Approaches to In Vitro Allergy Diagnosis. AB - Allergy diagnostics is being transformed by the advent of in vitro IgE testing using purified allergen molecules, combined with multiplex technology and biosensors, to deliver discriminating, sensitive, and high-throughput molecular diagnostics at the point of care. Essential elements of IgE molecular diagnostics are purified natural or recombinant allergens with defined purity and IgE reactivity, planar or bead-based multiplex systems to enable IgE to multiple allergens to be measured simultaneously, and, most recently, nanotechnology-based biosensors that facilitate rapid reaction rates and delivery of test results via mobile devices. Molecular diagnostics relies on measurement of IgE to purified allergens, the "active ingredients" of allergenic extracts. Typically, this involves measuring IgE to multiple allergens which is facilitated by multiplex technology and biosensors. The technology differentiates between clinically significant cross-reactive allergens (which could not be deduced by conventional IgE assays using allergenic extracts) and provides better diagnostic outcomes. Purified allergens are manufactured under good laboratory practice and validated using protein chemistry, mass spectrometry, and IgE antibody binding. Recently, multiple allergens (from dog) were expressed as a single molecule with high diagnostic efficacy. Challenges faced by molecular allergy diagnostic companies include generation of large panels of purified allergens with known diagnostic efficacy, access to flexible and robust array or sensor technology, and, importantly, access to well-defined serum panels form allergic patients for product development and validation. Innovations in IgE molecular diagnostics are rapidly being brought to market and will strengthen allergy testing at the point of care. PMID- 26143390 TI - Engineering the Microbiome: a Novel Approach to Immunotherapy for Allergic and Immune Diseases. AB - The incidence of immune disorders is growing parallel with practices associated with westernization, such as dietary changes, increased use of antibiotics, or elevated rates of Cesarean section. These practices can significantly impact the gut microbiota, the collection of bacteria residing in the human gastrointestinal tract, and subsequently disrupt the delicate balance existing between commensal flora and host immune responses. Restoring this balance by modifying the microbiota has thus emerged as a promising therapeutic approach. Here, we discuss the interaction between gut commensals and immunity, along with the potential of different interventions on the microbiota as treatment for inflammatory and allergic diseases. PMID- 26143393 TI - Control Process for Manufacturing and Standardization of Allergenic Molecules. AB - It is widely accepted that the success of the allergen immunotherapy (AIT), beyond clinical parameters such as dose, dosage regimen, or compliance, depends on the quality and composition of the final products used in the vaccines. Allergenic vaccines are pharmaceutical preparations derived from the natural sources which contain the allergenic components responsible for allergic sensitization. The selection of the appropriate allergenic sources must be a requirement. They suffer a dramatic transformation during the manufacturing process which renders a biologically standardized final product. The inclusion of the appropriate control analyses in the manufacturing process has demonstrated to be an efficient method to guarantee the quality and homogeneity of the final product as well as being a very useful tool for saving time and money. In this context, in the last years, the Regulatory Agencies have released specific guidelines to guarantee the manufacturing of the most appropriate products for the treatment of patients. PMID- 26143392 TI - The Etiology and Pathogenesis of Chronic Rhinosinusitis: a Review of Current Hypotheses. AB - Chronic rhinosinusitis (CRS) is a broad clinical syndrome that is characterized by prolonged mucosal inflammation of the nose and paranasal sinuses, and is typically divided into two subtypes based on the presence or absence of nasal polyps. The etiology and pathogenesis of both forms remain areas of active research. Over the last 15 years, a number of hypotheses have been proposed to explain all or part of the clinical CRS spectrum. These hypotheses reflect the concept that CRS results from a dysfunctional interplay between individual host characteristics and factors exogenous to the host. Six broad theories on CRS etiology and pathogenesis are discussed as follows: (1) the "fungal hypothesis," (2) the "superantigen hypothesis," (3) the "biofilm hypothesis," and (4) the "microbiome hypothesis," all of which emphasize key environmental factors, and (5) the "eicosanoid hypothesis" and (6) the "immune barrier hypothesis," which describe specific host factors. These theories are reviewed, and the evidence supporting them is critically appraised. PMID- 26143394 TI - Distinguishing Asthma Phenotypes Using Machine Learning Approaches. AB - Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as 'asthma endotypes'. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies. PMID- 26143395 TI - Recent Trends in Occupational Contact Dermatitis. AB - Occupational contact dermatitis (OCD) remains prevalent among workers and impacts quality of life and workability. The purpose of this review is to summarize the recent advances in occupational contact dermatitis as well as potential hazardous agents in the workplaces causing OCD. The review covers new developments in the epidemiology, etiology, diagnosis, and management of occupational contact dermatitis. This article also provides updated information on the prevalence of work-related skin symptoms and on new contact allergens among working population. It is emphasized that in the context of prevention of OCD, special attention should be focused on the identified high-risk occupational groups, especially healthcare workers and hairdressers starting with the apprentices. Current approaches include working out the standards and guidelines to improve the education, knowledge, diagnosis, and management of OCD based on a multidisciplinary team of medical specialists and an employer. PMID- 26143397 TI - Phosphate starvation enhances the pathogenesis of Bacillus anthracis. AB - Identifying the factors responsible for survival and virulence of Bacillus anthracis within the host is prerequisite for the development of therapeutics against anthrax. Host provides several stresses as well as many advantages to the invading pathogen. Inorganic phosphate (Pi) starvation within the host has been considered as one of the major contributing factors in the establishment of infection by pathogenic microorganisms. Here, we report for the first time that Pi fluctuation encountered by B. anthracis at different stages of its life cycle within the host, contributes significantly in its pathogenesis. In this study, Pi starvation was found to hasten the onset of infection cycle by promoting spore germination. After germination, it was found to impede cell growth. In addition, phosphate starved bacilli showed more antibiotic tolerance. Interestingly, phosphate starvation enhanced the pathogenicity of B. anthracis by augmenting its invasiveness in macrophages in vitro. B. anthracis grown under phosphate starvation were also found to be more efficient in establishing lethal infections in mouse model as well. Phosphate starvation increased B. anthracis virulence by promoting the secretion of primary virulence factors like protective antigen (PA), lethal factor (LF) and edema factor (EF). Thus, this study affirms that besides other host mediated factors, phosphate limitation may also contribute B. anthracis for successfully establishing itself within the host. This study is a step forward in delineating its pathophysiology that might help in understanding the pathogenesis of anthrax. PMID- 26143396 TI - Asthma Pharmacogenomics: 2015 Update. AB - There is evidence that genetic factors are implicated in the observed differences in therapeutic responses to the common classes of asthma therapy such as beta2 agonists, corticosteroids, and leukotriene modifiers. Pharmacogenomics explores the roles of genetic variation in drug response and continues to be a field of great interest in asthma therapy. Prior studies have focused on candidate genes and recently emphasized genome-wide association analyses. Newer integrative omics and system-level approaches have recently revealed novel understanding of drug response pathways. However, the current known genetic loci only account for a fraction of variability in drug response and ongoing research is needed. While the field of asthma pharmacogenomics is not yet fully translatable to clinical practice, ongoing research should hopefully achieve this goal in the near future buttressed by the recent precision medicine efforts in the USA and worldwide. PMID- 26143399 TI - Molecular cloning, expression of a galectin gene in Pacific white shrimp Litopenaeus vannamei and the antibacterial activity of its recombinant protein. AB - Galectins play crucial roles in innate immune responses in invertebrate by recognizing and eliminating microinvaders. In this study, a cDNA encoding a galectin in the Pacific white shrimp (L. vannamei) was identified and characterized. A recombinant variant of this lectin, rLvgalectin, was expressed in the model organism P. pastoris and its expression was confirmed by Western blot. Biochemical assays indicated that the recombinant protein antibacterial rLvgalectin activity and was expressed in all of the organism's tested tissues Injection of the bacterium V. alginolyticus into L. vannamei induced hemocytes upregulation of Lvgalectin. The recombinant Lvgalectin protein (rLvgalectin) could bind various microorganism including Gram-positive bacteria, Gram-negative bacteria and yeast. And it revealed antimicrobial activity against the test Gram positive bacteria, Gram-negative bacteria, but did not inhibit the growth of fungus Pichia pastoris. Moreover, rLvgalectin could significantly enhance the clearance activity of V. alginolyticus in vivo. In vivo challenge experiments showed that the recombinant rLvgalectin protein can significantly reduce the mortalities of V. alginolyticus injection. Furthermore, Compared to their wild type counterparts, Lvgalectin-silenced shrimp exhibited increased mortality and hemocyte apoptosis, decreased bacterial clearance ability and total hemocyte counts, and stronger expression of Lvp53, LvproPO, LvPEN3, and LvCrustin following V. alginolyticus challenge. Taken together, these results suggest that galectin is important in the innate immune response of shrimp to pathogens infection. PMID- 26143398 TI - ATP binding by NLRP7 is required for inflammasome activation in response to bacterial lipopeptides. AB - Nucleotide-binding oligimerization domain (NOD)-like receptors (NLRs) are pattern recognition receptors (PRRs) involved in innate immune responses. NLRs encode a central nucleotide-binding domain (NBD) consisting of the NAIP, CIITA, HET-E and TP1 (NACHT) domain and the NACHT associated domain (NAD), which facilitates receptor oligomerization and downstream inflammasome signaling. The NBD contains highly conserved regions, known as Walker motifs, that are required for nucleotide binding and hydrolysis. The NLR containing a PYRIN domain (PYD) 7 (NLRP7) has been recently shown to assemble an ASC and caspase-1-containing high molecular weight inflammasome complex in response to microbial acylated lipopeptides and Staphylococcus aureus infection. However, the molecular mechanism responsible for NLRP7 inflammasome activation is still elusive. Here we demonstrate that the NBD of NLRP7 is an ATP binding domain and has ATPase activity. We further show that an intact nucleotide-binding Walker A motif is required for NBD-mediated nucleotide binding and hydrolysis, oligomerization, and NLRP7 inflammasome formation and activity. Accordingly, THP-1 cells expressing a mutated Walker A motif display defective NLRP7 inflammasome activation, interleukin (IL)-1beta release and pyroptosis in response to acylated lipopeptides and S. aureus infection. Taken together, our results provide novel insights into the mechanism of NLRP7 inflammasome assembly. PMID- 26143400 TI - Biosorption of arsenic from groundwater using Vallisneria gigantea plants. Kinetics, equilibrium and photophysical considerations. AB - Arsenic (V) uptake from groundwater by using Vallisneria gigantea plants was studied using batch experiments. Reflectance and fluorescence of intact plants were investigated and changes in photophysical properties following arsenic absorption were reported. Good correlations have been found between arsenic concentration in groundwater and parameters derived from reflectance and fluorescence measurements. This system reached its equilibrium after seven days when the removal quantities were strongly dependent on the initial arsenic concentration. Interestingly, Vallisneria plants were able to accumulate from 100 to 600 mg As kg(-1) in roots and fronds although the translocation factors were low (0.6-1.6). Kinetic data for biosorption process followed a first-order law. At low arsenic concentrations the uptake in plants was governed by diffusion aspects. Langmuir, Freundlich and Dubinin-Radushkevich models were applied and results demonstrated that arsenic uptake was better described by the Langmuir model. As a final remark we concluded that a plant of this species should be able to remove 1mg As per week. PMID- 26143401 TI - Assessment and improvement of biotransfer models to cow's milk and beef used in exposure assessment tools for organic pollutants. AB - The aim of this study was to assess and improve the accuracy of biotransfer models for the organic pollutants (PCBs, PCDD/Fs, PBDEs, PFCAs, and pesticides) into cow's milk and beef used in human exposure assessment. Metabolic rate in cattle is known as a key parameter for this biotransfer, however few experimental data and no simulation methods are currently available. In this research, metabolic rate was estimated using existing QSAR biodegradation models of microorganisms (BioWIN) and fish (EPI-HL and IFS-HL). This simulated metabolic rate was then incorporated into the mechanistic cattle biotransfer models (RAIDAR, ACC-HUMAN, OMEGA, and CKow). The goodness of fit tests showed that RAIDAR, ACC-HUMAN, OMEGA model performances were significantly improved using either of the QSARs when comparing the new model outputs to observed data. The CKow model is the only one that separates the processes in the gut and liver. This model showed the lowest residual error of all the models tested when the BioWIN model was used to represent the ruminant metabolic process in the gut and the two fish QSARs were used to represent the metabolic process in the liver. Our testing included EUSES and CalTOX which are KOW-regression models that are widely used in regulatory assessment. New regressions based on the simulated rate of the two metabolic processes are also proposed as an alternative to KOW-regression models for a screening risk assessment. The modified CKow model is more physiologically realistic, but has equivalent usability to existing KOW regression models for estimating cattle biotransfer of organic pollutants. PMID- 26143402 TI - Safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for relapse-prevention of bipolar II depression: A randomized, double blind, parallel-group, prospective study. AB - OBJECTIVE: Compare the safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for preventing depressive relapse in bipolar II disorder. METHODS: Subjects >=18 years old with bipolar II depression (n=129) were randomized to double-blind venlafaxine or lithium monotherapy for 12 weeks. Responders with a >=50% reduction in depression score were continued for an additional 6 months of relapse-prevention monotherapy. Primary outcome was depressive relapse during continuation monotherapy. Secondary outcomes included sustained response rate from initiation of treatment to study end-point, relapse hazard, time to relapse, change in mania ratings, and frequency of treatment emergent sub-syndromal hypomania and/or depressive episodes. RESULTS: Venlafaxine produced greater sustained response rate versus lithium (p<0.0001); however, there was no difference in relapse rate for venlafaxine (7.5%) versus lithium (26.7%) (p=0.079); relapse hazard (p=0.073), or time to relapse (p=0.090) between treatment conditions during continuation monotherapy. There were no group differences in mania rating scores over time and no difference in frequency or duration of syndromal or sub-syndromal hypomanic episodes. There were more sub syndromal depressive episodes during lithium monotherapy (p=0.03). LIMITATIONS: Sample size was limited by the lower sustained response rate for lithium versus venlafaxine; study was not specifically powered to detect differences in treatment-emergent hypomanic or depressive episodes between groups. CONCLUSION: Results suggest that continuation venlafaxine monotherapy may provide similar prophylactic effectiveness relative to lithium, with no difference in treatment emergent hypomanic episodes and without the need for frequent serum lithium level and metabolic monitoring. Larger, prospective trials are needed to confirm these observations. PMID- 26143403 TI - Celebrity suicide on the railway network: Can one case trigger international effects? AB - BACKGROUND: After the railway suicide of the German national goalkeeper Robert Enke in 2009, a significant increase of railway suicides was observed nationally. This study analyses whether this incident also triggered copycat effects in other European countries. Additionally, media coverage proxied by Google Trends and long-term changes taking into account general changes in suicide rates and kilometres driven by trains were examined. METHODS: The numbers of railway suicides before and after Enke's suicide were analysed for short and long-term periods (2 weeks and 2 years post-event) across five European countries. Incidence ratios and resulting percentage changes were computed. RESULTS: Similar to Germany, there were significant short and long-term effects for the combined data of the four other countries (increase of 93.9%; p=0.004 and 16.7%; p=0.003). There was no indication that long-term effects are a mere reflection of an overall increase in suicide frequencies or due to increased numbers of kilometres driven by trains. Analyses on country level revealed heterogeneous results. LIMITATIONS: Due to incomplete data, analyses regarding age and gender were not performed. Media coverage was only proxied by a Google Trends analysis. The study includes a small sample of European countries. CONCLUSIONS: Enke's suicide in 2009 was followed by increasing train suicide numbers in Europe. Although this incident may have reinforced an existing European trend of growing railway suicides, an international copycat effect and/or an increased overall awareness about this particular suicide method appears to be one likely explanation for the changes. PMID- 26143404 TI - Depression in patients with alcohol use disorders: Systematic review and meta analysis of outcomes for independent and substance-induced disorders. AB - BACKGROUND: In patients with an alcohol use disorder, depression is commonly categorised as independent (ID) or substance-induced (SID). It is not established whether these conditions respond differently to treatment. METHODS: MEDLINE, Embase and Cochrane databases from 1980 to 2014 were searched for studies on alcohol use disorders with coexisting depressive symptoms. Meta-analyses were conducted using random effects models, to derive pooled effect estimates of the change in depression during treatment and the effect of antidepressant therapy. RESULTS: Twenty-two studies met inclusion criteria for the review, of which 11/22 were included in the meta-analysis. All studies reported a large improvement in depression symptom score, most of which occurred within the first 3-6 weeks of treatment. The amount of improvement during follow up was similar in studies on ID in comparison to those in undifferentiated depression. Evidence on the outcome for SID was limited. The effect size of antidepressant therapy compared to placebo was 0.25 (0.06, 0.44) for ID and 0.08 (-0.31, 0.47) for SID or undifferentiated depression. LIMITATIONS: Few studies examined the natural history and treatment response of SID. There was heterogeneity between studies, which was partly explained by baseline depression severity. CONCLUSIONS: Treatment for depression co-occurring with an alcohol use disorder is associated with a large early improvement in depression, even if depression is believed to be independent of drinking. The effect of antidepressant therapy on depression in patients with alcohol use disorders is modest, with stronger evidence in ID. PMID- 26143405 TI - The role of negative mood induction on working memory capacity in individuals putatively at risk for bipolar disorder: A pilot study. AB - OBJECTIVE: Bipolar disorder (BD) is characterized by cognitive deficits. Usually individuals at risk for BD do not exhibit such deficits but they might be evident under cognitive or emotionally stressful conditions. To our knowledge this is the first study examining working memory capacity under mood induction in individuals at risk for BD. METHODS: Using the Hypomanic Personality Scale (HPS) 68 participants out of an initial pool of 148 students were divided into groups at high and low risk for BD. They completed twice a Dual Task Paradigm (DTP) task assessed under high and low cognitive load prior to and following a negative mood induction. RESULTS: As expected stimuli incongruency, high cognitive load and mood induction increased response times. Contrary to our hypothesis the mood induction did not differentially affect at-risk individuals. However, they generally reacted faster to neutral stimuli compared to those at low risk. CONCLUSIONS: While we replicated former results related to the DTP, we did not find evidence for the hypothesis that individuals putatively at risk for BD will be more affected by negative mood when doing such a cognitive task. Replication using a larger sample is needed which should also examine whether changes in positive mood might more relevant in the context of risk for mania. PMID- 26143406 TI - Baseline cognitive function does not predict the treatment outcome of electroconvulsive therapy (ECT) in late-life depression. AB - BACKGROUND: No prior study has investigated whether impairment of specific cognitive functions at baseline may predict the short-term treatment outcome of electroconvulsive therapy (ECT) in elderly non-demented patients with major depression (MD). METHODS: This longitudinal cohort study included 65 elderly patients with unipolar or bipolar MD, aged 60-85 years, treated with formula based ECT. Treatment outcome was assessed using the 17-item Hamilton Rating Scale for Depression (HRSD17). Cognitive function at baseline was assessed using nine neuropsychological tests or subtests measuring information processing speed, verbal learning and memory, and aspects of executive function. RESULTS: A poorer performance on the word reading task of the Color Word Interference Test rendered higher odds of achieving remission during the ECT course (p=0.021). Remission was defined as an HRSD17 score of 7 or less. There were no other significant associations between the treatment outcome of ECT and cognitive performance parameters assessed at baseline. LIMITATIONS: The limited number of subjects may have reduced the generalizability of the findings. Multiple statistical tests increase the risk for making a type I error. CONCLUSIONS: How well patients perform on neuropsychological tests at baseline is most likely not a predictor of, or otherwise not significantly associated with the treatment outcome of formula-based ECT in elderly patients with MD. PMID- 26143407 TI - Pleomorphic adenoma of spermatic cord. PMID- 26143408 TI - End stage renal disease and kidney transplant in patients with anorectal malformation: is there an alternative route? AB - BACKGROUND/PURPOSE: Mortality from end stage renal disease (ESRD) in patients with anorectal malformation (ARM) is reported to be between 2.5 and 6%. The risk differs depending on the type of ARM (6.4% "high" vs. 1.1% "low"). The purpose of this study was to review the characteristics of the ARM patients who received a kidney transplant (KT) to potentially identify if any modifiable factors existed that may have prevented ESRD. METHODS: The Colorectal Center and the kidney transplant databases at Cincinnati Children's Hospital were queried to identify patients with ARM and a KT. Data obtained included: gender, type of ARM, associated characteristics, urological status at birth, surgical and medical management, age at KT, and possible interventions that could have prevented or delayed the KT. RESULTS: 20 patients with ARM who underwent KT were identified. 16 were females, thirteen of whom had a cloaca; the average common channel length in these patients was 5 cm, ranging from 2 to 8 cm. Nine cloaca patients had hydrocolpos and 5 of them were not drained at birth. Eleven patients presented with renal failure at birth. Five patients with cloaca had common channel atresia/stenosis, 2 male patients had severe urethral atresia, 2 patients had absent bladders, and 1 patient had bilateral blind ureters. At birth, 6 patients had single functional kidneys, 4 had bilateral hydronephrosis with megaureters, 3 patients had bilateral dysplastic kidneys, 1 patient had a single kidney with hydronephrosis, and 1 patient had a single hypoplastic kidney. The average age at KT was 10.9 years (range 2-21 years.); in 3 patients, the KT was performed before the repair of the ARM. One patient died after the KT and one patient had rejection following the KT and is currently on hemodialysis. CONCLUSION: Patients with cloaca and recto-bladderneck fistula are the type of ARM with the highest risk for ESRD. Kidney failure at birth, common channel/urethral atresia, hydrocolpos, single kidney, and ectopic ureters represent high risk for future KT. Even when missed opportunities were identified, the impact of interventions to prevent or delay the onset of ESRD could not be proven. PMID- 26143409 TI - Transition from childhood to adolescence: Quality of life changes 6 years later in patients born with anorectal malformations. AB - BACKGROUND/PURPOSE: Disease-specific quality of life (QoL) may be more or less relevant when children enter preadolescence/adolescence. Few attentions have been given to development and transition periods. Aim of the present longitudinal study is to evaluate ARM specific changes in QoL and the stability of QoL over 6 years. METHODS: Questionnaires were sent to families of the AIMAR Association (in 2007 and in 2013/2014). They included the Hirschsprung's Disease/ARM QoL Questionnaire (HAQL, [1]). Rank correlations and within group comparisons for the HAQL subscales were conducted analyzing the scores of time 1 vs time 2. Gender effects were tested. RESULTS: 134 parents answered the questionnaires at time 1 and 73 at time 2. Results of the repeated Analyses of Variance indicated improvements in the continence subscales ("Presence of Diarrhea," "Fecal Continence"). QoL significantly worsened in "Social and Emotional Functioning" and in "Body Image" areas. The analysis of stability of change indicates that QoL scores remain stable, with the exception of the Body Image area. CONCLUSIONS: Despite improvements in the continence areas, parents reported worse levels of QoL in the psychosocial areas, as their child grow. As patients grow, they might have more difficulties in daily and social activities, and feel more frequently ashamed and more dissatisfied with their body. PMID- 26143410 TI - Male cloaca malformation: rare variant of anorectal malformation. AB - PURPOSE: Experience with male cloaca (MC), a single opening in perineum for passage of urine and meconeum is described. METHODS: Cases of MC were ambispectively studied, prospectively from July 2007 to April 2015 and retrospectively for last three decades. RESULTS: Seven cases of MC were identified, between the ages of newborn-4 years (median 10 days). Two missed cases underwent a colostomy, posterior sagittal anorectoplasty, and urethroplasty. Two cases underwent perineal urethrostomy and anoplasty followed by urethroplasty. In one case, part of the rectal wall was used to form urethral tube and urethrostomy. For three recent cases, posterior sagittal anorectourethroplasty was done with mobilization of rectal pouch and common channel, separation of common wall between the urethra and rectum, urethroplasty varying from 1.5 to 3 cm, perineal body reconstruction, perineal urethrostomy and anoplasty. Follow-up of 6 patients varied from 3 months to 23 years. One case is lost to follow-up. Three patients have completed repair. Complications included a discharging sinus and a urethral fistula in one case each. One patient died while awaiting urethroplasty. Two patients are awaiting formal urethroplasty. CONCLUSION: With familiarity of varying anatomy of MC, early recognition can avoid a neonatal colostomy in selected patients. PMID- 26143411 TI - VACTERL association in anorectal malformation: effect on the outcome. AB - PURPOSE: Anorectal malformations (ARM) can commonly occur in association with other congenital anomalies or as part of the combined anomaly. The present study aims to assess the outcome of patients with ARM and patients with ARM in VACTERL association. METHODS: A 12-year retrospective analysis of all patients treated at a single tertiary children's institution with a diagnosis of ARM. We identified and compared patients with ARM to those with ARM in VACTERL association (3 or more anomalies). Data were collected for both groups to assess type of ARM, urinary incontinence (UI), constipation, soiling, dietary/laxative treatment, bowel management (BM) and surgical complications. Type of lesion and clinical outcomes were classified according to Krickenbeck International classification. Patients lost to follow-up, dead or not yet toilet-trained (or <4 years old) were excluded. RESULTS: One hundred ninety-eight patients were identified, 174 enrolled in the study. Lesions were classified for each study group (VACTERL- vs VACTERL+) as perineal fistulas (36.4 vs 9.7%, p = 0.0028), rectourethral fistulas (prostatic and bulbar) (23.1 vs 38.7%, p = ns), rectovesical fistulas (3.5 vs 9.7%, p = ns), rectovestibular fistulas (19.6 vs 22.6%, p = ns), cloacal malformations (4.9 vs 9.7%, p = ns), no fistula (4.9 vs 3.2%, p=), others (7.7 vs 6.4%, p = ns). The frequency of both dietary/laxative treatment and BM, as well as surgical complications were significantly higher in patients with VACTERL. CONCLUSIONS: The coexistence of VACTERL anomalies negatively affects not only the surgical outcome but also the bowel functioning. Therefore, a dedicated follow-up is strongly recommended. Further studies are needed to assess if this has an impact on the quality of life of these patients. PMID- 26143412 TI - Factors associated with age at pyeloplasty in children with ureteropelvic junction obstruction. AB - OBJECTIVES: Our objectives were to: (1) delineate factors associated with surgery at <1 year and (2) determine if early intervention was associated with increased risk of readmission. METHODS: We conducted a retrospective review of children age 0-18 years with a diagnosis of UPJ obstruction who underwent pyeloplasty from 1/1/1999 to 9/1/2009 using the PHIS database. Data collected included patient factors (race, gender, insurance type, APR-DRG severity of illness) and hospital factors (annual case volume, census region, academic status). Outcomes assessed were: age at surgery and hospital readmission within 1 year of surgery. Data were analyzed using logistic regression and Cox PH for multivariate analyses. RESULTS: 4499 children met study criteria. Minority race (OR 1.55), male gender (OR 1.49), public insurance (OR 1.37), high severity of illness (OR 3.60), Southern region (OR 1.44), and low hospital volume (OR 1.37) were significant predictors of early surgery (p < 0.05). Only early surgery (HR 2.42; 95% CI 1.67-3.49 2.42) was associated with increased risk of readmission. CONCLUSIONS: In children with UPJ obstruction, age at surgery is associated with patient demographic and hospital factors. Early surgery is associated with higher rates of readmission, suggesting that variations in age at surgery may be associated with significant differences in outcomes. PMID- 26143413 TI - Supervisor behaviour and its associations with employees' health in Europe. AB - OBJECTIVES: To estimate the magnitude of the associations between different facets of supervisor behaviour and several health-related outcomes, and to assess whether these associations are mediated by known occupational health factors. METHODS: Cross-sectional data from the European Working Conditions Survey were analysed by generalised linear mixed models (n = 32,770). Six regression models were estimated. Dependent variables include musculoskeletal (upper body, lower limbs, backache) and psychosomatic symptoms (stress and self-assessed general health). Independent variables correspond to several facets of supervisor behaviours such as supervisor support, feedback on work, ability to solve conflicts, encouragement to participate in decisions, and known occupational risk and protective factors. RESULTS: Even though supervisor behaviour is mediated by several known occupational risk factors, it still accounts for a substantial proportion of explained variance. The order of magnitude of associations was comparable to the strength of associations of known occupational risk factors. Odds ratios vary from 0.79 95% CI [0.73-0.86] to 1.12 95% CI [0.97-1.29] for dichotomous dependent variables. Regression coefficients vary from -0.22 95% CI [ 0.28 to -0.17] to 0.07 95% CI [0.04-0.10] for metric dependent variables. Results suggest that good conflict solving skills, supervisor's work-planning ability, and a participative leadership style have the strongest predictive power regarding all health-related outcomes considered. CONCLUSION: Supervisor behaviour seems to play a non-negligible role from an occupational health perspective concerning the prevalence of musculoskeletal and psychosomatic symptoms. Results suggest that supervisor behaviour should be routinely assessed and monitored, especially among occupational groups reporting a lower quality of supervisor behaviours. PMID- 26143414 TI - Value of Whole Brain Computed Tomography Perfusion for Predicting Outcome after TIA or Minor Ischemic Stroke. AB - INTRODUCTION: About 15% of patients with transient ischemic attack (TIA) or minor ischemic stroke have functional impairment after 3 months. We studied the role of whole brain computed tomography perfusion (WB-CTP) in the emergency diagnosis of TIA or minor stroke in predicting disability at 3 months. METHODS: We included patients with ongoing symptoms of a TIA or minor stroke with a National Institutes of Health Stroke Scale (NIHSS) score less than 4 who were evaluated with noncontrast CT (NCCT), CT angiography (CTA), and WB-CTP within 24 hours of symptom onset. Patients treated with thrombolysis or a premorbid modified Rankin Scale (mRS) score greater than 1 were excluded. The association between clinical or imaging features and disability (mRS score >=2) at 3 months was analyzed with Poisson regression. Potential additional prognostic value of WB-CTP was assessed with logistic regression. RESULTS: We included 115 patients in 2012 to 2013. Median age was 68 years, and 66% were men. At 3 months, 20 patients (17%) were disabled. NIHSS score on admission (relative risk [RR], 3.6; 95% confidence interval [CI], 1.4-9.3), female sex (RR, 2.4; 95% CI, 1.1-5.3), early ischemic changes on NCCT (RR, 5.0; 95% CI, 2.6-9.9), extracranial or intracranial vessel stenosis >=50% on CTA (RR, 3.0; 95% CI, 1.4-6.4), and perfusion abnormalities on WB-CTP (RR, 11.4; 95% CI, 4.6-28.2) were associated with disability at 3 months. In multivariable analysis, the relation between perfusion abnormalities and poor outcome remained essentially the same. WB-CTP showed prognostic value in addition to proved clinical and imaging predictors of disability. CONCLUSIONS: WB-CTP is useful to identify patients with TIA or minor ischemic stroke at high risk of functional impairment at 3-month follow-up. PMID- 26143415 TI - Neurochecks as a Biomarker of the Temporal Profile and Clinical Impact of Neurologic Changes after Intracerebral Hemorrhage. AB - BACKGROUND: We sought to determine whether a quantitative neurocheck biomarker could characterize the temporal pattern of early neurologic changes after intracerebral hemorrhage (ICH), and the impact of those changes on long-term functional outcomes. METHODS: We enrolled cases of spontaneous ICH in a prospective observational study. Patients underwent a baseline Glasgow Coma Scale (GCS) assessment, then hourly neurochecks using the GCS in a neuroscience intensive care unit. We identified a period of heightened neurologic instability by analyzing the average hourly rate of GCS change over 5 days from symptom onset. We used a multivariate regression model to test whether those early GCS score changes were independently associated with 3-month outcome measured by the modified Rankin Scale (mRS). RESULTS: We studied 13,025 hours of monitoring from 132 cases. The average rate of neurologic change declined from 1.0 GCS points per hour initially to a stable baseline of .1 GCS points per hour beyond 12 hours from symptom onset (P < .05 for intervals before 12 hours). Change in GCS score within the initial 12 hours was an independent predictor of mRS at 3 months (odds ratio, .81 [95% confidence interval, .66-.99], P = .043) after adjustment for age, hematoma volume, hematoma location, initial GCS, and intraventricular hemorrhage. CONCLUSIONS: Neurochecks are effective at detecting clinically important neurologic changes in the intensive care unit setting that are relevant to patients' long-term outcomes. The initial 12 hours is a period of frequent and prognostically important neurologic changes in patients with ICH. PMID- 26143417 TI - Elastolytic Actinic Giant Cell Granuloma. AB - Actinic granuloma and annular elastolytic giant cell granuloma are different terms used to define skin lesions characterized by elastolysis, elastophagocytosis, and multinucleated giant cell infiltrate. The clinical appearance varies from papules to annular plaques. Although elastolytic actinic giant cell granuloma shares some clinical features with granuloma annulare, they can be differentiated by histopathologic findings. The disease is initiated by an immune response triggered by different factors that alter the elastic tissue. The course tends to be chronic, with variable response to treatments, although spontaneous remission may occur. Diabetes mellitus is the systemic disease most frequently associated with this condition. PMID- 26143416 TI - Granuloma Annulare. AB - Granuloma annulare (GA) is a noninfectious granulomatous skin condition that can present with a variety of cutaneous morphologies. It is characterized by collagen degeneration, mucin deposition, and palisaded or interstitial histiocytes. Although the mechanism underlying development of GA is unknown, studies point to a cell-mediated hypersensitivity reaction to an as-yet undetermined antigen. Systemic associations with diabetes, thyroid disorders, lipid abnormalities, malignancy, and infection are described in atypical GA. Treatment is divided into localized skin-directed therapies and systemic immunomodulatory or immunosuppressive therapies. The selected treatment modality should be based on disease severity, comorbid conditions, consideration of potential side effects, and patient preference. PMID- 26143418 TI - Necrobiosis Lipoidica. AB - Necrobiosis lipoidica is a granulomatous condition presenting as indolent atrophic plaques, often on the lower extremities. There is a multitude of case reports suggesting possible associations and documenting different therapeutic alternatives with varied success. Important complications include ulceration and the development of squamous cell carcinoma. The disease course is often indolent and recurrent despite treatment. This article reviews the etiopathogenesis, clinical presentations, and evidence for treatment alternatives of this condition. PMID- 26143419 TI - Rheumatoid Nodules. AB - Rheumatoid nodules are a common manifestation of rheumatoid arthritis. These lesions are often easily identified based on typical diagnostic features and characteristic locations. When biopsied, nodules have a characteristic histologic appearance. Uncommonly, rheumatoid nodules can occur in systemic locations. There is no evidence that systemic therapy treats underlying rheumatoid nodules. Paradoxically, methotrexate and possibly tumor necrosis factor inhibitors can increase nodule development. Treatment of rheumatoid nodules is often not necessary, unless patients are experiencing pain or there is interference of mechanical function. This review outlines the available data on and associations of rheumatoid nodules. PMID- 26143420 TI - Reactive Granulomatous Dermatitis: A Review of Palisaded Neutrophilic and Granulomatous Dermatitis, Interstitial Granulomatous Dermatitis, Interstitial Granulomatous Drug Reaction, and a Proposed Reclassification. AB - The terms "palisaded neutrophilic and granulomatous dermatitis," "interstitial granulomatous dermatitis," and the subset "interstitial granulomatous drug reaction" are a source of confusion. There exists substantial overlap among the entities with few strict distinguishing features. We review the literature and highlight areas of distinction and overlap, and propose a streamlined diagnostic workup for patients presenting with this cutaneous reaction pattern. Because the systemic disease associations and requisite workup are similar, and the etiopathogenesis is poorly understood but likely similar among these entities, we propose the simplified unifying term "reactive granulomatous dermatitis" to encompass these entities. PMID- 26143421 TI - Sarcoidosis. AB - Sarcoidosis is a disease characterized by noncaseating granulomatous infiltration of 1 or more organs. In North America, after the lungs and thoracic lymph nodes, the skin is the next most commonly involved organ. Data from multiple studies indicate a coaction between genetic and environmental factors in immunologically susceptible hosts. The disease's many clinical manifestations and course vary greatly and are influenced by race, ethnicity, and gender. In the skin, the lesions of sarcoidosis are classified as specific when noncaseating granulomas are present, and nonspecific when there is an inflammatory reaction pattern devoid of granulomas. PMID- 26143422 TI - Cutaneous Manifestations of Crohn Disease. AB - Awareness of the extraintestinal manifestations of Crohn disease is increasing in dermatology and gastroenterology, with enhanced identification of entities that range from granulomatous diseases recapitulating the underlying inflammatory bowel disease to reactive conditions and associated dermatoses. In this review, the underlying etiopathology of Crohn disease is discussed, and how this mirrors certain skin manifestations that present in a subset of patients is explored. The array of extraintestinal manifestations that do not share a similar pathology, but which are often seen in association with inflammatory bowel disease, is also discussed. Treatment and pathogenetic mechanisms, where available, are discussed. PMID- 26143423 TI - Orofacial Granulomatosis. AB - Orofacial granulomatosis (OFG) is an uncommon chronic inflammatory disorder of the orofacial region. It is characterized by subepithelial noncaseating granulomas and has a spectrum of possible clinical manifestations ranging from subtle oral mucosal swelling to permanent disfiguring fibrous swelling of the lips and face. Etiopathogenesis is unknown. A range of systemic granulomatous disorders, including Crohn disease and sarcoidosis, may cause orofacial manifestations that cannot be distinguished from those of OFG. Treatment of OFG has proven difficult and unsatisfactory, with no single therapeutic model showing consistent efficacy in reducing orofacial swelling and mucosal inflammation. PMID- 26143424 TI - Granulomatous Rosacea and Periorificial Dermatitis: Controversies and Review of Management and Treatment. AB - Granulomatous rosacea and periorificial dermatitis are common skin conditions affecting the face. This article examines the historical origin, causes, clinical presentation, and management strategies for these entities. PMID- 26143425 TI - Adult Orbital Xanthogranulomatous Disease: A Review with Emphasis on Etiology, Systemic Associations, Diagnostic Tools, and Treatment. AB - Adult orbital xanthogranulomatous diseases are rare entities and encompass a group of disorders with varying manifestations that are poorly understood. Taken as a group, there are non-Langerhans histiocytic disorders (type II) that are diagnosed histologically by the presence of foamy histiocytes, Touton giant cells, and varying degrees of fibrosis. Based on the accompanying systemic associations, there are 4 main categories of adult xanthogranulomatous disease: adult-onset xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. Herein, we discuss the etiopathogenesis, systemic associations, methods of diagnosis, and treatment options for these disorders. PMID- 26143426 TI - Adult Xanthogranuloma, Reticulohistiocytosis, and Rosai-Dorfman Disease. AB - Adult xanthogranuloma presents most commonly as an orange-tan firm solitary nodule with no systemic manifestations. Recently, some cases have been reported in conjunction with lymphoproliferative disorders. Adult reticulohistiocytosis classically presents as red to yellow-red dermal nodules. In the multicentric form, lesions have a predilection for hands and elbows, with a classic coral bead periungual presentation, and are often associated with symmetric erosive arthritis, particularly of the hands and wrists. The presentation and course of Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, can vary. The classic presentation is extensive, painless bilateral cervical lymphadenopathy, but some cases have been entirely extranodal. PMID- 26143427 TI - Granulomatous Vasculitis. AB - Vasculitides are uncommon disorders, characterized by inflammation of the blood vessels resulting either in ischemia or hemorrhage. They are commonly classified as small-, medium-, or large-vessel vasculitides. Antineutrophil cytoplasmic antibody-associated vasculitis is an important group of small-vessel vasculitis. This group includes granulomatous vasculitides, namely, granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and nongranulomatous vasculitis, namely, microscopic polyangiitis (MPA). Classic polyarteritis nodosa (PAN) is a granulomatous medium-vessel vasculitis. This review discusses the classification, etiopathogenesis, clinical features, and management of GPA, MPA, EGPA and PAN. PMID- 26143428 TI - Granulomatous Lymphoproliferative Disorders: Granulomatous Slack Skin and Lymphomatoid Granulomatosis. AB - Granulomatous cutaneous T-cell lymphomas (CTCL) and lymphomatoid granulomatosis are considered granulomatous lymphoproliferative disorders. The most common types of granulomatous CTCL are granulomatous mycosis fungoides and granulomatous slack skin. Lymphomatoid granulomatosis is a rare Epstein-Barr virus driven lymphoproliferative disorder. This article reviews the etiopathogenesis, clinical presentation, systemic associations, and management of both granulomatous slack skin syndrome and lymphomatoid granulomatosis. PMID- 26143429 TI - Foreign Body Granulomas. AB - A large list of foreign substances may penetrate the skin and induce a foreign body granulomatous reaction. These particles can enter the skin by voluntary reasons or be caused by accidental inclusion of external substances secondary to cutaneous trauma. In these cases, foreign body granulomas are formed around such disparate substances as starch, cactus bristles, wood splinters, suture material, pencil lead, artificial hair, or insect mouthparts. The purpose of this article is to update dermatologists, pathologists, and other physicians on the most recent etiopathogenesis, clinical presentations, systemic associations, evaluation, and evidence-based management concerning foreign body granulomatous reactions of skin. PMID- 26143430 TI - Granulomatous Drug Eruptions. AB - Granuloma formation is usually regarded as a means of defending the host from persistent irritants of either exogenous or endogenous origin. Noninfectious granulomatous disorders of the skin encompass a challenging group of diseases owing to their clinical and histologic overlap. Drug reactions characterized by a granulomatous reaction pattern are rare, and defined by a predominance of histiocytes in the inflammatory infiltrate. This review summarizes current knowledge on the various types of granulomatous drug eruptions, focusing on the 4 major types: interstitial granulomatous drug reaction, drug-induced accelerated rheumatoid nodulosis, drug-induced granuloma annulare, and drug-induced sarcoidosis. PMID- 26143431 TI - Tuberculosis and Leprosy: Classical Granulomatous Diseases in the Twenty-First Century. AB - Leprosy and tuberculosis are chronic mycobacterial infections that elicit granulomatous inflammation. Both infections are curable, but granulomatous injury to cutaneous structures, including cutaneous nerves in leprosy, may cause permanent damage. Both diseases are major global concerns: tuberculosis for its high prevalence and mortality, and leprosy for its persistent global presence and high rate of neuropathic disability. Cutaneous manifestations of both leprosy and tuberculosis are frequently subtle and challenging in dermatologic practice and often require a careful travel and social history and a high index of suspicion. PMID- 26143432 TI - Nontuberculous Mycobacteria: Skin and Soft Tissue Infections. AB - Skin and soft tissue infections caused by nontuberculous mycobacteria are increasing in incidence. The nontuberculous mycobacteria are environmental, acid fast bacilli that cause cutaneous infections primarily after trauma, surgery and cosmetic procedures. Skin findings include abscesses, sporotrichoid nodules or ulcers, but also less distinctive signs. Important species include Mycobacterium marinum and the rapidly growing mycobacterium: M. fortuitum, M. abscessus and M. chelonae. Obtaining tissue for mycobacterial culture and histopathology aids diagnosis. Optimal therapy is not well-established, but is species-dependent and generally dictated by susceptibility studies. Management often includes use of multiple antibiotics for several months and potential use of adjunctive surgery. PMID- 26143433 TI - New World and Old World Leishmania Infections: A Practical Review. AB - Leishmaniasis is a parasitic infection endemic to more than 90 countries worldwide. As travel to endemic areas increases, dermatologists need to keep this entity in the differential for any chronic skin lesion in persons who may have had a possible exposure for any duration. It can be difficult to diagnose because manifestations are varied and sometimes subclinical. This article discusses the current state of epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment options. A special focus is placed on cutaneous manifestations and their treatment. PMID- 26143434 TI - Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections. AB - Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline. PMID- 26143435 TI - Clinical Atlas of Granulomatous Disorders. PMID- 26143436 TI - Granulomatous Disorders of the Adult Skin: Twenty-First Century. PMID- 26143437 TI - Evaluation of immunomodulatory activity of two potential probiotic Lactobacillus strains by in vivo tests. AB - Here we evaluate the immunomodulatory function of two potential probiotic strains, Lactobacillus salivarius CICC 23174 and Lactobacillus plantarum CGMCC 1.557. Mice were fed with each Lactobacillus strain at different doses for several consecutive days. The effects of the two probiotic strains on immune organs, immune cells and immune molecules were investigated on days 10 and 20. Both Lactobacillus strains increased the spleen index, improved the spleen lymphocyte transformation rate, enhanced sIgA production and improved the number of CD11c(+) CD80(+) double-positive cells. L. plantarum CGMCC 1.557 was the more active strain in enhancing the phagocytic activity of macrophages, while, L. salivarius CICC 23174 was the more effective strain at maintaining the Th1/Th2 balance. This study suggests that these two Lactobacillus strains have beneficial effects on regulation of immune responses, which has promising implications for the development of ecological agents and functional foods. PMID- 26143438 TI - The influence of number of counts in the myocardium in the determination of reproducible functional parameters in gated-SPECT studies simulated with GATE. AB - Myocardial perfusion gated-single photon emission computed tomography (gated SPECT) imaging is used for the combined evaluation of myocardial perfusion and left ventricular (LV) function. The aim of this study is to analyze the influence of counts/pixel and concomitantly the total counts in the myocardium for the calculation of myocardial functional parameters. MATERIAL AND METHODS: Gated SPECT studies were performed using a Monte Carlo GATE simulation package and the NCAT phantom. The simulations of these studies use the radiopharmaceutical (99m)Tc-labeled tracers (250, 350, 450 and 680 MBq) for standard patient types, effectively corresponding to the following activities of myocardium: 3, 4.2, 5.4 8.2 MBq. All studies were simulated using 15 and 30s/projection. The simulated data were reconstructed and processed by quantitative-gated-SPECT software, and the analysis of functional parameters in gated-SPECT images was done by using Bland-Altman test and Mann-Whitney-Wilcoxon test. RESULTS: In studies simulated using different times (15 and 30s/projection), it was noted that for the activities for full body: 250 and 350 MBq, there were statistically significant differences in parameters Motility and Thickness. For the left ventricular ejection fractio n (LVEF), end-systolic volume (ESV) it was only for 250 MBq, and 350 MBq in the end-diastolic volume (EDV), while the simulated studies with 450 and 680MBq showed no statistically significant differences for global functional parameters: LVEF, EDV and ESV. CONCLUSION: The number of counts/pixel and, concomitantly, the total counts per simulation do not significantly interfere with the determination of gated-SPECT functional parameters, when using the administered average activity of 450 MBq, corresponding to the 5.4 MBq of the myocardium, for standard patient types. PMID- 26143439 TI - Assessment and care for non-medical risk factors in current antenatal health care. AB - OBJECTIVE: this study aims to identify current practice in risk assessment, current antenatal policy and referral possibilities for non-medical risk factors (lifestyle and social risk factors), and to explore the satisfaction among obstetric caregivers in their collaboration with non-obstetrical caregivers. DESIGN: cross-sectional study SETTING: Dutch antenatal care system PARTICIPANTS: community midwives from 139 midwifery practices and gynaecologists, hospital based midwives, and trainees in obstetrics from 38 hospitals. MEASUREMENTS AND FINDINGS: results were analysed with chi(2) tests and unpaired t-tests. Caregivers universally screened upon lifestyle risk factors (e.g. smoking or drug use), whereas the screening for social risk factors (e.g. social support) was highly variable. As national guidelines are absent, local protocols were reported to be used for screening on non-medical risk factors in more than 40%. Caregivers stated multidisciplinary protocols to be a prerequisite for assessment of non medical risk factors. Only 22% of the caregivers used predefined criteria to define when patients should be discussed multidisciplinary. CONCLUSION: despite their relevance, non-medical risk factors remain an underexposed topic in antenatal risk factor screening in both the community and hospital-based care setting. Implications for practice Structural antenatal risk assessment for non medical risk factors with subsequent consultation opportunities is advocated, preferably based on a multidisciplinary guideline. PMID- 26143440 TI - Pivotal preclinical trial of the spheroid reservoir bioartificial liver. PMID- 26143441 TI - Serum-based tracking of de novo initiated liver cancer progression reveals early immunoregulation and response to therapy. AB - BACKGROUND & AIMS: Liver inflammatory diseases associated with cancer promoting somatic oncogene mutations are increasing in frequency. Preclinical cancer models that allow for the study of early tumor progression are often protracted, which limits the experimental study parameters due to time and expense. Here we report a robust inexpensive approach using Sleeping Beauty transposition (SBT) delivery of oncogenes along with Gaussia Luciferase expression vector GLuc, to assess de novo liver tumor progression, as well as the detection of innate immune responses or responses induced by therapeutic intervention. METHODS: Tracking de novo liver tumor progression with GLuc was demonstrated in models of hepatocellular carcinoma (HCC) or adenoma (HCA) initiated by hydrodynamic delivery of SBT oncogenes. RESULTS: Rising serum luciferase levels correlated directly with increasing liver tumor burden and eventual morbidity. Early detection of hepatocyte apoptosis from mice with MET+CAT transfected hepatocytes was associated with a transient delay in HCC growth mediated by a CD8(+) T-cell response against transformed hepatocytes. Furthermore, mice that lack B cells or macrophages had an increase in TUNEL(+) hepatocytes following liver MET transfection demonstrating that these cells provide protection from MET-induced hepatocyte apoptosis. Treatment with IL-18+IL-12 of mice displaying established HCC decreased tumor burden which was associated with decreased levels of serum luciferase. CONCLUSIONS: Hydrodynamic delivery of the SBT vector GLuc to hepatocytes serves as a simple blood-based approach for real-time tracking of pathologically distinct types of liver cancer. This revealed tumor-induced immunologic responses and was beneficial in monitoring the efficacy of therapeutic interventions. PMID- 26143442 TI - Reply to: "Pivotal preclinical trial of the spheroid reservoir bioartificial liver". PMID- 26143443 TI - HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase. AB - BACKGROUND & AIMS: Maintenance of the covalently closed circular HBV DNA (cccDNA) that serves as a template for HBV transcription is responsible for the failure of antiviral therapies. While studies in chronic hepatitis patients have shown that high viremia correlates with hyperacetylation of cccDNA-associated histones, the molecular mechanisms controlling cccDNA stability and transcriptional regulation are still poorly understood. This study aimed to decipher the role of chromatin and chromatin modifier proteins on HBV transcription. METHODS: We analyzed the chromatin structure of actively transcribed or silenced cccDNA by infecting primary human hepatocytes and differentiated HepaRG cells with wild-type virus or virus deficient (HBVX-) for the expression of hepatitis B virus X protein (HBx), that is required for HBV expression. RESULTS: In the absence of HBx, HBV cccDNA was transcriptionally silenced with the concomitant decrease of histone 3 (H3) acetylation and H3K4me3, increase of H3 di- and tri-methylation (H3K9me) and the recruitment of heterochromatin protein 1 factors (HP1) that correlate with condensed chromatin. SETDB1 was found to be the main histone methyltransferase responsible for the deposition of H3K9me3 and HBV repression. Finally, full transcriptional reactivation of HBVX- upon HBx re-expression correlated with an increase of histone acetylation and H3K4me3, and a concomitant decrease of HP1 binding and of H3K9me3 on the cccDNA. CONCLUSION: Upon HBV infection, cellular mechanisms involving SETDB1-mediated H3K9me3 and HP1 induce silencing of HBV cccDNA transcription through modulation of chromatin structure. HBx is able to relieve this repression and allow the establishment of active chromatin. PMID- 26143445 TI - Psychophsyiological reactivity during uncertainty and ambiguity processing in high and low worriers. AB - BACKGROUND AND OBJECTIVES: Intolerance of uncertainty (IU) has been linked to Generalized Anxiety Disorder (GAD), but studies experimentally manipulating uncertainty have mostly failed to find differences between GAD patients and controls, possible due to a lack of distinction between uncertainty and ambiguity. This study therefore investigated reactivity to ambiguity in addition to uncertainty in high worriers (HW) and low worriers (LW). We hypothesized an interpretation bias between the groups during ambiguity tasks, while uncertainty would facilitate threat processing of subsequent aversive stimuli. METHODS: HW (N = 23) and LW (N = 23) completed a paradigm comprising the anticipation and perception of pictures with dangerous, safe, or ambiguous content. Anticipatory cues were certain (always correct information about the following picture) or uncertain (no information). Subjective ratings, reaction times and skin conductance responses (SCRs) were recorded. RESULTS: HW rated particularly ambiguous pictures as more aversive and showed longer reaction times to all picture conditions compared to LW. SCRs were also larger in HW compared to LW, particularly during uncertain but also safe anticipation. No group differences were observed during perception of stimuli. LIMITATIONS: All participants were female. HW was used as subclinical phenotype of GAD. CONCLUSIONS: Intolerance of ambiguity seems to be related to individual differences in worry and possibly to the development of GAD. Threat-related interpretations differentiating HW and LW occurred particularly for ambiguous pictures but were not accompanied by increased autonomic arousal during the picture viewing. This disparity between subjective rating and arousal may be the result of worrying in response to intolerance of uncertainty, restraining physiological responses. PMID- 26143444 TI - Association of baseline vitamin D levels with clinical parameters and treatment outcomes in chronic hepatitis B. AB - BACKGROUND & AIMS: The relationship between vitamin D levels and chronic hepatitis B (CHB) infection and treatment outcomes are poorly elucidated. We measured pre-treatment serum vitamin D (25-hydroxyvitamin D3; 25[OH]D3) levels and determined their association with clinical parameters and treatment outcomes in active CHB patients without advanced liver disease enrolled in a global clinical trial. METHODS: Patients were randomly assigned to either 48 weeks of tenofovir disoproxil fumarate (TDF) plus peginterferon alfa-2a (PegIFN), TDF plus PegIFN for 16 weeks followed by TDF for 32 weeks, PegIFN for 48 weeks, or TDF for 120 weeks. Univariate and multivariate analyses were conducted to determine associations between vitamin D, baseline factors, and week 48 clinical outcome. RESULTS: Of 737 patients, 35% had insufficient (?20 but <31 ng/ml) and 58% had deficient (<20 ng/ml) vitamin D levels. In univariate analysis, lower vitamin D levels were significantly associated with the following baseline parameters: younger age, lower uric acid levels, HBeAg-positive status, lower calcium levels, blood draw in winter or autumn, and HBV genotype D. On multivariate analysis, only HBV genotype, season of blood draw, calcium level, and age retained their association. High baseline level of vitamin D was associated with low HBV DNA, normal ALT and HBsAg at week 48 independent of treatment groups, but the association, with the exception of ALT, became statistically insignificant after adjusting for age, gender, HBeAg and HBV genotype. CONCLUSIONS: Abnormally low vitamin D levels are highly prevalent among untreated, active CHB patients. Baseline vitamin D levels are not associated with treatment outcomes, but were associated with normal ALT. PMID- 26143447 TI - The qualities of homeopathy. PMID- 26143446 TI - Learned, instructed and observed pathways to fear and avoidance. AB - BACKGROUND AND OBJECTIVES: Conditioned fear may emerge in the absence of directly experienced conditioned stimulus (CS)--unconditioned stimulus (US) pairings. Here, we compared three pathways by which avoidance of the US may be acquired both directly (i.e., through trial-and-error instrumental learning) and indirectly (i.e., via verbal instructions and social observation). METHODS: Following fear conditioning in which CS+ was paired with shock and CS- was unpaired, three separate groups of participants learned by direct experience (Instrumental-learning), were instructed about (Instructed-learning), or observed (Observational-learning) a demonstrator performing an avoidance response that canceled upcoming US (shock) presentations. Groups were then tested in extinction with presentations of the directly experienced CS+ and CS-, and either a novel CS (Instrumental and observational groups) or an instructed CS (instructed-group). RESULTS: Similar to instrumental learning, results demonstrate that avoidance may be acquired via instructions and social observation in the absence of directly learning that an avoidance response prevents the US. Retrospective US expectancy ratings were modulated by the assumed presence or absence of avoidance. Overall, these findings suggest that instrumental-, instructed-, and observational learning pathways to avoidance in humans are similar. LIMITATIONS: Alternative experimental designs would permit direct comparison between the pathways for stimuli with no prior experience of fear conditioning, and trial-by-trial US expectancy ratings would help track the modulation of fear by avoidance pathway. CONCLUSIONS: Instrumental-, instructed-, and observational-learning pathways of avoidance are similar. Findings may have implications for understanding the etiology of clinical avoidance in anxiety. PMID- 26143448 TI - Model validity of randomised placebo-controlled trials of individualised homeopathic treatment. AB - BACKGROUND: Though potentially an important limitation in the literature of randomised controlled trials (RCTs) of homeopathy, the model validity of homeopathic treatment (MVHT) has not previously been systematically investigated. OBJECTIVE: As an integral part of a programme of systematic reviews, to assess MVHT of eligible RCTs of individualised homeopathic treatment. METHODS: From 46 previously identified papers in the category, 31 papers (reporting a total of 32 RCTs) were eligible for systematic review and were thus the subject of the study. For each of six domains of assessment per trial, MVHT was judged independently by three randomly allocated assessors from our group, who reached a final verdict by consensus discussion as necessary. RESULTS: Nineteen trials were judged overall as 'acceptable' MVHT, nine as 'uncertain' MVHT, and four as 'inadequate' MVHT. CONCLUSIONS: These results do not support concern that deficient MVHT has frequently undermined the published findings of RCTs of individualised homeopathy. However, the 13 trials with 'uncertain' or 'inadequate' MVHT will be a focus of attention in supplementary meta-analysis. New RCTs of individualised homeopathy must aim to maximise MVHT and to enable its assessment through clear reporting. PMID- 26143449 TI - Utilization of psychotropic drugs by patients consulting for sleeping disorders in homeopathic and conventional primary care settings: the EPI3 cohort study. AB - BACKGROUND: Utilization of sedative hypnotic drugs for sleeping disorders (SD) raises concerns, particularly among older people. This study compared utilization of conventional psychotropic drugs for SD among patients seeking care from general practitioners (GPs) who strictly prescribe conventional medications (GP CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was a French population-based cohort study of GPs and their patients consulting for SD, informed through the Pittsburgh sleep quality index (PSQI) questionnaire. Information on psychotropic drugs utilization was obtained from a standardized telephone interview at inclusion, one, three and 12 months. RESULTS: 346 patients consulting for SD were included. Patients in the GP-Ho group experienced more often severe SD (41.3%) than patients in the GP-CM group (24.3%). Adjusted multivariate analyses showed that patients who chose to be managed by GP-Ho were less likely to use psychotropic drugs over 12 months as opposed to the GP-CM group, with Odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.14 to 0.42. Patients in the GP-Mx group also used less psychotropic drugs but the result was not statistically significant (OR = 0.67; 95% CI: 0.39-1.16). Rates of clinical improvement of the SD did not differ between groups. CONCLUSIONS: Patients with SD who chose to consult GPs certified in homeopathy consumed less psychotropic drugs and had a similar evolution of their condition to patients treated with conventional medical management. This result may translate in a net advantage with reduction of adverse events related to psychotropic drugs. PMID- 26143450 TI - The homeopathic choice for children: a qualitative research on the decision making process of the families. AB - AIM: To explore the experiences of parents who chose homeopathic treatment for their children, with particular regard to the decision-making process within the family and the availability of conventional and homeopathic healthcare services. METHODS: Semi-structured interview with parents immediately after or before the homeopathic visit at the Homeopathic Clinic of Campo di Marte Hospital of Lucca (Italy) from1st March, 2012 to 18 July 2012. Answers were analyzed by frequency of response and grouped into main areas: 1. Choice of homeopathy. 2. Intra-family dynamics. 3. Behaviour in emergency situations. 4. The relationship with the homeopathic doctor. 5. The role of friends and acquaintances. 6. The 'cut off' of use of homeopathy. RESULTS: Parents who choose homeopathic treatments for their children are strongly influenced by context. The choice of homeopathy is usually made by mothers and is rarely hindered by fathers, grandparents or friends, whose approval is important and encourages parents to use homeopathy for their children, both for prevention and treatment. Easy access to the homeopathic doctor was frequently requested, especially for acute situations. CONCLUSION: This research confirms the importance of context in decision making processes. Other characteristics of families which use homeopathy, such as level of education, personal coping strategies and family context should be investigated. PMID- 26143451 TI - Some intrapersonal qualities of SA homeopaths who have established successful private practices. AB - PURPOSE: The purpose of the study was to explore the experiences of homeopaths who have established successful private practices in South Africa (SA) with the aim of identifying some of their intrapersonal qualities which may have contributed to their establishing a successful practice. METHOD: This was a qualitative phenomenological research design using in-depth interviews with homeopaths running successful private practices across 5 provinces in SA, which were digitally recorded. Of these, 18 were transcribed and analysed using a descriptive coding approach and strategies for phenomenological analysis. Themes and supporting categories are identified and described. FINDINGS: Homeopaths experiences suggest that they are authentic, self-aware, self-reflective and proactive. They experienced a need for self-care and support and further found that their integrity, positive attitude, self-discipline and passion, contributed to their success in practice. CONCLUSION: The intrapersonal qualities can be roughly divided between those that generate inner-support and those which aid homeopaths attain their goal of establishing a practice and are therefore crucial aspects of success generation. PMID- 26143452 TI - Data collection: Treat every variable as a treasure. AB - Collection of data concerning case histories is not yet common in homeopathy despite its great importance for this method. Computer program development progresses slowly and discussion about requirements is scarce. Two Dutch projects assessed Materia Medica of some homeopathic medicines and six homeopathic symptoms. Especially the second project relied heavily on data collection. In both projects much effort was spent on consensus between participating doctors. There was much variance between doctors despite our consensus efforts. Assessing causality seems the most important source of bias, there is also much variance in assessing symptoms. CONCLUSION: Data collection software should be developed step by-step, guided by close monitoring and feedback of participating practitioners. PMID- 26143453 TI - Syzygium jambolanum and Cephalandra indica homeopathic preparations inhibit albumin glycation and protect erythrocytes: an in vitro study. AB - BACKGROUND: Diabetes mellitus is a common endocrine disorder characterized by hyperglycemia eventually resulting in long-term complications. Increased glycation of proteins is implicated in the pathogenesis of complications. For treatment of diabetes, Syzygium jambolanum and Cephalandra indica are frequently prescribed in homeopathy. However their role in glycation is not well elucidated. The present study aimed to evaluate the role of these homeopathic preparations in glycation induced structural modifications and further to examine their cellular protection ability. METHODS: In human erythrocytes, in vitro mother tincture and dilutions of S. jambolanum (Sj f, 30c, 200c), C. indica (Ci f, 30c, 200c) and standard antiglycator (AG) were compared and their antiglycation potential assessed by the estimating different markers of glycation (frcutosamines, carbonyls, bound sugar), structural modifications (free amino and thiol group). Phytochemical characterization (total phenolic, flavonoids and glycosides contents) was performed. RESULTS: The homeopathic preparations have different mode of action on albumin glycation modifications. Sj f preparation demonstrated effective inhibition of all glycation, structural modifications except amino group protection. When dilutions were compared, Sj preparations showed reduction of glycation, structural modifications. All preparations showed significant erythrocyte protection. Sj f preparation exhibited noteworthy antiglycation and cell protection ability as compared to AG. CONCLUSION: These homeopathic preparations especially Sj f prevented glycation induced albumin modifications and subsequent toxicity in human eryrthrocytre in vitro. Further investigation of their potential as antiglycators is justified. PMID- 26143454 TI - Effects of Tarantula cubensis D6 on aflatoxin-induced injury in biochemical parameters in rats. AB - INTRODUCTION: Aflatoxins are toxic fungal metabolites that have adverse effects on humans and animals. Tarantula cubensis D6 is used as a homeopathic medicine for different purposes. The present study investigates the effects of Tarantula cubensis D6 on the oxidant-antioxidant balance and some biochemical parameters against exposure to aflatoxin. METHODS: Thirty-two Sprague-Dawley female rats were used and evenly divided into four groups. Group 1 served as control. Groups 2, 3, and 4 received 200 MUl/kg.bw/day Tarantula cubensis D6 (applied subcutaneously), 400 MUg/kg.bw/day total aflatoxin (approximately 80% AF B1, 10% AF B2, 6 %AF G1, and 4% AF G2), and 200 MUl/kg.bw/day Tarantula cubensis D6 plus 400 MUg/kg.bw/day total aflatoxin, respectively, for 28 days. At the end of 28 days, blood samples and some organs (liver, kidney, brain, and spleen) were taken from all the animals. Oxidative stress markers (MDA, SOD, CAT, GSH-Px) and some biochemical parameters (glucose, triglyceride, cholesterol, BUN, creatinine, AST, ALT and ALP, total protein, albumin) were evaluated in blood samples and tissues. RESULTS: Aflatoxin caused negative changes in all oxidative stress parameters and some biochemical parameters (glucose, triglyceride, cholesterol, creatinine, AST, ALT, ALP, total protein, albumin). Administration of Tarantula cubensis D6 partly alleviated aflatoxin-induced negative changes. CONCLUSIONS: Our results indicated that Tarantula cubensis D6 partially neutralized the deleterious effects of aflatoxin. PMID- 26143455 TI - Homeopathic remedies with antineoplastic properties have immunomodulatory effects in experimental animals. AB - BACKGROUND: Our previous work suggests that Thuja occidentalis, Carcinosinum and Ruta graveolens have antineoplastic properties. The mechanism of this action has not previously been studied. We studied the hypothesis that the mechanism of action is through the immune modulation. METHODS: We evaluated the effects of Thuja occidentalis, Carcinosinum and Ruta graveolens 1M, 200c and 30c on the immune system of Balb/c mice. The homeopathic preparations were administered orally for ten consecutive days. Haematological parameters (Total White Blood Cell (WBC) Count, Differential Count and Haemoglobin content), haematopoietic parameters (bone marrow cellularity and alpha-esterase positive cells) and immune parameters for antibody response and lymphoid cell proliferation were assessed using standard methods. Results were analysed by statistical comparison with the control. RESULTS: We observed significant enhancement of haematological parameters including total WBC count, haematopoietic parameters such as bone marrow cellularity and the number of alpha-esterase positive cells, other parameters of immune response such as circulating antibody titre and the number of plaque forming cells (PFC), particularly with higher dilutions of Thuja and Ruta. Enhanced proliferation of B and T lymphoid cells was also observed. No toxic effects were observed. CONCLUSIONS: The results suggest immunomodulatory activity of homeopathic preparations in high dilution. This may be a mechanism through which homeopathic preparations act. PMID- 26143456 TI - Risk factors for antepartum stillbirth: a case-control study in Nepal. AB - BACKGROUND: Globally, at least 2.65 million stillbirths occur every year, of which more than half are during the antepartum period. The proportion of intrapartum stillbirths has substantially declined with improved obstetric care; however, the number of antepartum stillbirths has not decreased as greatly. Attempts to lower this number may be hampered by an incomplete understanding of the risk factors leading to the majority of antepartum stillbirths. We conducted this study in a tertiary hospital in Nepal to identify the specific risk factors that are associated with antepartum stillbirth in this setting. METHODS: This case-control study was conducted between July 2012 and September 2013. All women who had antepartum stillbirths during this period were included as cases, while 20 % of all women delivering at the hospital were randomly selected and included as referents. Information on potential risk factors was taken from medical records and interviews with the women. Logistic regression analysis was completed to determine the association between those risk factors and antepartum stillbirth. RESULTS: During the study period, 4567 women who delivered at the hospital were enrolled as referents, of which 62 had antepartum stillbirths and were re-categorized into the case population. In total, there were 307 antepartum stillbirths. An association was found between the following risk factors and antepartum stillbirth: increasing maternal age (aOR 1.0, 95 % CI 1.0-1.1), less than five years of maternal education (aOR 2.4, 95 % CI 1.7-3.2), increasing parity (aOR 1.2, 95 % CI 1.0-1.3), previous stillbirth (aOR 2.6, 95 % CI 1.6 4.4), no antenatal care attendance (aOR 4.2, 95 % CI 3.2-5.4), belonging to the poorest family (aOR 1.3, 95 % CI 1.0-1.8), antepartum hemorrhage (aOR 3.7, 95 % CI 2.4-5.7), maternal hypertensive disorder during pregnancy (aOR 2.1, 95 % CI 1.5-3.1), and small weight-for-gestational age babies (aOR 1.5, 95 % CI 1.2-2.0). CONCLUSION: Lack of antenatal care attendance, which had the strongest association with antepartum stillbirth, is a potentially modifiable risk factor, in that increasing the access to and availability of these services can be targeted. Antenatal care attendance provides an opportunity to screen for other potential risk factors for antepartum stillbirth, as well as to provide counseling to women, and thus, helps to ensure a successful pregnancy outcome. CLINICAL TRIAL REGISTRATION: ISRCTN97846009 (url. www.isrctn.com/ISRCTN97846009 ). PMID- 26143457 TI - Transient Elastography for the Detection of Liver Damage in Patients with HIV. AB - INTRODUCTION: Highly active antiretroviral therapy (HAART) is effective and well tolerated, but hepatotoxicity is relatively common. Different non-invasive methods are available for detecting liver fibrosis in patients with chronic liver disease. METHODS: Patients who were HIV positive and who had given their informed consent were included in this cross-sectional study. Transient elastography [FibroScan((r)) (FS); Echosens], serum hyaluronic acid (HA), Hepascore (HS), Fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) were used to detect liver fibrosis in the patients. The agreement between FS and the other methods was evaluated. To observe the hepatotoxicity of HAART, patients with chronic viral hepatitis B or C were excluded by detection of hepatitis B surface antigens and hepatitis C virus antibodies. Patients with chronic alcohol intake were excluded by measuring carbohydrate-deficient transferrin (CDT). FS correlation with the duration of therapy with protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) was evaluated. RESULTS: Overall, 203 patients were included in the study. The agreement between the different tests ranged from 64% to 77%: FS vs. HA, 72%; FS vs. APRI, 74%; FS vs. HS, 77%; and FS vs. FIB-4, 64%. After excluding patients with chronic hepatitis B or C and elevated CDT, 153 patients remained for studying the hepatotoxicity of HAART. A significant correlation of FS with the duration of medication intake was observed for PIs (P = 0.026; r = 0.18). NRTI and NNRTI therapy duration did not correlate with FS. CONCLUSIONS: The agreement between FS and other tests ranged from 64% to 77%. A significant correlation was found between liver stiffness and the duration of therapy with PIs, which underlines the known hepatotoxicity of this substance group. FUNDING: Heinz-Ansmann Foundation. PMID- 26143458 TI - Fabrication of a facile electrochemical biosensor for hydrogen peroxide using efficient catalysis of hemoglobin on the porous Pd@Fe3O4-MWCNT nanocomposite. AB - In this work, a sensitive amperometric biosensor for hydrogen peroxide based on synergetic catalysis of hemoglobin and porous Pd@Fe3O4-MWCNT nanocomposite has been constructed. With attention to the utilities of large surface area and outstanding catalytic performance, Pd@Fe3O4-MWCNT nanocomposite was employed as the nano-stabilizer for the immobilization of hemoglobin (Hb). The immobilized Hb on the surface of nanocomposite as an electrochemical biosensor efficiently catalyzed the reduction of hydrogen peroxide, amplified the electrochemical signal and enhanced the sensitivity. Results of voltammetry and electrochemical impedance examinations showed that the nanocomposite could enhance the electron conductivity and provide more sites for the immobilization of Hb. A linear response from 0.2-500 uM with detection limit of 0.063 uM for hydrogen peroxide was achieved. The apparent Michaelis-Menten constant Kapp(M) value was 21 uM. Thus, the nanocomposite could be applied for fabrication of a third generation biosensor for hydrogen peroxide with high sensitivity, selectivity and low detection limit. The excellent performance of the biosensor indicated its promising prospect as a valuable tool in simple and fast hydrogen peroxide detection in environmental and clinical applications. PMID- 26143459 TI - Real-time monitoring of geosmin and 2-methylisoborneol, representative odor compounds in water pollution using bioelectronic nose with human-like performance. AB - A bioelectronic nose for the real-time assessment of water quality was constructed with human olfactory receptor (hOR) and single-walled carbon nanotube field-effect transistor (swCNT-FET). Geosmin (GSM) and 2-methylisoborneol (MIB), mainly produced by bacteria, are representative odor compounds and also indicators of contamination in the water supply system. For the screening of hORs which respond to these compounds, we performed CRE-luciferase assays of the two odorants in heterologous cell system. Human OR51S1 for GSM and OR3A4 for MIB were selected, and nanovesicles expressing the hORs on surface were produced from HEK 293 cell. Carbon nanotube field-effect transistor was functionalized with the nanovesicles. The bioelectronic nose was able to selectively detect GSM and MIB at concentrations as low as a 10 ng L(-1). Furthermore, detection of these compounds from the real samples such as tap water, bottled water and river water was available without any pretreatment processes. PMID- 26143460 TI - Different shades of cholesterol: Gold nanoparticles supported on MoS2 nanoribbons for enhanced colorimetric sensing of free cholesterol. AB - In the present study, we manifest that traditionally used gold nanoparticles when supported on molybdenum disulfide nanoribbons matrix (MoS2 NRs-Au NPs) show synergistically enhanced intrinsic peroxidase like catalytic activity and can catalyze the oxidation of 3,3',5,5' tetramethyl benzidine by H2O2 to produce a highly sensitive blue shade product depending on level of free cholesterol, when tested on complex system of human serum. Further the system attests appreciable kinetics, owing to Km value as low as 0.015 mM and better loading capacity (Vmax=6.7*10(-6) M s(-1)). Additionally, the proposed system is stable for weeks with ability to perform appreciably in wide pH (3-6) and temperature range (25-60 degrees C). Utilizing this potential, the present work proposes a cholesterol detection color wheel which is used along with cost effective cholesterol detection strips fabricated out of proposed MoS2 NRs-Au NPs system for quick and reliable detection of free cholesterol using unaided eye. PMID- 26143461 TI - Ultrasensitive strategy based on PtPd nanodendrite/nano-flower-like@GO signal amplification for the detection of long non-coding RNA. AB - Highly up-regulated in liver cancer (HULC) is a novel promising noninvasive biomarker for hepatocellular carcinoma (HCC), which is a kind of long non-coding RNAs (lncRNAs). But traditional methods limited HULC clinical detection for ownself drawbacks. Development a new HULC detection approach is urgent and necessary. Electrochemical nucleic acid sensor based on different signal amplification strategies with high sensitivity, fast, simple, and convenient, may solve this problem. Herein, we propose a novel strategy based on Pt-Pd bimetallic nanodendrites/nanoflower-like clusters on graphene oxide/Au/horseradish peroxidase (PtPd BND/BNF@GO/Au/HRP) to enhance the catalytic efficiency and sensitivity. And Au particles were simultaneously and separately capped with thionine or detection probe, which increase the binding amount of detection probe and decrease the electronic background. The results indicated that the catalytic effect was noticeably elevated and that the biosensor provides ultrasensitive detection for the lncRNA HULC. The linear calibration of the biosensor ranged from 1.00*10(-3) to 1.00*10(3) pM/mL, and the limit of detection was 0.247 fM/mL. The lncRNA biosensor based on the PtPd BND/BNF@GO/Au/HRP/Au/thionine exhibited acceptable reproducibility and clear selectivity. This strategy may provide a new alternative for clinical HCC diagnosis through the detection of HULC. PMID- 26143462 TI - A split G-quadruplex-based DNA nano-tweezers structure as a signal-transducing molecule for the homogeneous detection of specific nucleic acids. AB - A portable method of specific nucleic acid detection would be very useful for monitoring public health in a variety of settings for point-of-care and point-of need testing. However, conventional methods for the detection of nucleic acids are not ideal for use in the field, as they require skilled operators and complex equipment. Here, we constructed a method for specific nucleic acid detection using a split G-quadruplex (Gq) structure that can recognize target nucleic acids without competitive reactions in a bimolecular reaction and directly produce a detectable signal based on peroxidase activity. We developed a single signal transducing molecule with a split Gq-based DNA-nano tweezers (NT) structure that self-assembles from three single-stranded DNAs through simple mixing, and detects its target without requiring any washing steps. A model target, a partial norovirus mRNA (NV-RNA), was specifically recognized by the split Gq-based DNA NT, causing it to undergo a structural change that restored its peroxidase activity. The peroxidase activity was measured by following the oxidation of 2,2' azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), which gave a greenish colorimetric response, and was proportional to the NV-RNA concentration. The lower detection limit was 4 nM. Our results demonstrated the feasibility of detecting specific nucleic acids with a split Gq-based DNA-NT structure as a nucleic acid signal-transducing molecule in a homogenous assay format. Also the target recognition sites of split Gq-based DNA-NT can easily be designed without delicate optimization of tweezers structure. Thus a split Gq-based DNA-NT technique is readily applicable to a basic platform for the development of a portable device. PMID- 26143463 TI - MoS2 nanosheet-based fluorescent biosensor for protein detection via terminal protection of small-molecule-linked DNA and exonuclease III-aided DNA recycling amplification. AB - A new MoS2 nanosheet-based fluorescent biosensor for protein detection is developed. This method combines the terminal protection of small-molecule-linked DNA (TPSMLD) and exonuclease III (Exo III)-aided DNA recycling amplification to convert protein assay into the highly sensitive detection of DNA. Taking the streptavidin (SA)-biotin system as a model, a detection limit of 0.67 ng mL(-1) SA is obtained with a good selectivity. The study demonstrated here not only offers simple, sensitive and selective detection method for protein assay, but also will expand the application of the emerging 2D nanomaterials into biological assay. PMID- 26143464 TI - Whole-cell biosensor for label-free detection of GPCR-mediated drug responses in personal cell lines. AB - Deciphering how genetic variation in drug targets such as G protein-coupled receptors (GPCRs) affects drug response is essential for precision medicine. GPCR signaling is traditionally investigated in artificial cell lines which do not provide sufficient physiological context. Patient-derived cell lines such as lymphoblastoid cell lines (LCLs) could represent the ideal cellular model system. Here we describe a novel label-free, whole-cell biosensor method for characterizing GPCR-mediated drug responses in LCLs. Generally, such biosensor technology is deemed only compatible with adherent cell lines. We optimized and applied the methodology to study cellular adhesion properties as well as GPCR drug responses in LCLs, which are suspension cells. Coating the detector surface with the extracellular matrix protein fibronectin resulted in cell adherence and allowed detection of cellular responses. A prototypical GPCR present on these cells, i.e. the cannabinoid receptor 2 (CB2), was selected for pharmacological characterization. Receptor activation with the agonist JWH133, blockade by antagonist AM630 as well as downstream signaling inhibition by PTX could be monitored sensitively and receptor-specifically. Potencies and effects were comparable between LCLs of two genetically unrelated individuals, providing the proof-of-principle that this biosensor technology can be applied to LCLs, despite their suspension cell nature, in order to serve as an in vitro model system for the evaluation of individual genetic influences on GPCR-mediated drug responses. PMID- 26143465 TI - Investigating pipeline and state of the art blood glucose biosensors to formulate next steps. AB - Ten years on from a review in the twentieth issue of this journal, this contribution assess the direction research in the field of glucose sensing for diabetes is headed and various technologies to be seen in the future. The emphasis of this review was placed on the home blood glucose testing market. After an introduction to diabetes and glucose sensing, this review analyses state of the art and pipeline devices; in particular their user friendliness and technological advancement. This review complements conventional reviews based on scholarly published papers in journals. PMID- 26143466 TI - Nitrogen and sulfur co-doped carbon dots for highly selective and sensitive detection of Hg (II) ions. AB - Nitrogen and sulfur co-doped carbon dots (N,S/C-dots) with high fluorescence quantum yields (FLQY, 25%) was successfully synthesized by a one-step microwave assisted method. In comparison with nitrogen doped C-dots (N/C-dots) prepared using the same method, the resulting N,S/C-dots featured small particle size, uniform surface state, insensitive FL properties to excitation wavelengths and environmental conditions, negligible cytotoxicity and excellent biocompatibility. Simultaneous doping of N and S effectively promoted electron-transfer and coordination interaction between N,S/C-dots and Hg(2+). Thus, when used as fluorescence probe for Hg(2+) label-free detection, the resulting N,S/C-dots showed good detection sensitivity and ion selectivity. The limit of detection was 2 MUM; among 15 metal ions investigated, only Fe(3+) showed interference to the Hg(2+) detection. Fortunately, this interference could be effectively shielded using a chelating agent sodium hexametaphoshpate. The applicability of N,S/C-dots as fluorescence probe for Hg(2+) detection in lake water and tap water was demonstrated. Finally, based on its favorable features of negligible cytotoxicity and excellent biocompatibility, the N,S/C-dots were successfully applied to probe Hg(2+) in living cells, which broaden its application in biological system. PMID- 26143467 TI - Novel voltammetric and impedimetric sensor for femtomolar determination of lysozyme based on metal-chelate affinity immobilized onto gold nanoparticles. AB - In this study, we reported iminodiacetic acid-copper ion complex (IDA-Cu) immobilized onto gold nanoparticles (GNPs)-modified glassy carbon electrode as a novel electrochemical platform for selective and sensitive determination of lysozyme (Lys). IDA-Cu complex acted as an efficient recognition element capable of capturing Lys molecules. GNPs acts as a substrate to immobilize IDA-Cu coordinative complex and its interaction with Lys leds to a great signal amplification through measuring changes in differential pulse voltammetric (DPV) peak current of [Fe(CN)6](3-/4-) redox probe. Upon the recognition of the Lys to the IDA-Cu, the peak current decreased due to the hindered electron transfer reaction on the electrode surface. Under optimum condition, it was found that the proposed method could detect Lys at wide linear concentration range (0.1 pM to 0.10 mM) with detection limit of 60 fM. Furthermore, electrochemical impedance spectroscopy (EIS) detection of Lys was demonstrated as a simple and rapid alternative analytical technique with detection limit of 80 fM at concentration range up to 0.1mM. In addition, the proposed sensor was satisfactorily applied to the determination of Lys in real samples such as hen egg white. The proposed modified electrode showing the high selectivity, good sensitivity and stability toward Lys detection may hold a great promise in developing other electrochemical sensors based on metal-chelate affinity complexes. PMID- 26143468 TI - A ratiometric fluorescent quantum dots based biosensor for organophosphorus pesticides detection by inner-filter effect. AB - In this work, we develop a novel and sensitive sensor for the detection of organophosphorus pesticides based on the inner-filter effect (IFE) between gold nanoparticles (AuNPs) and ratiometric fluorescent quantum dots (RF-QDs). The RF QDs has been designed by hybridizing two differently colored CdTe QDs, in which the red emissive QDs entrapped in the silica sphere acting as the reference signal, and the green emissive QDs covalently attached on the silica surface serving as the response signal.The fluorescence of RF-QDs could be quenched by AuNPs based on IFE. Protamine could effectively turn on the fluorescence due to the electrostatic attraction between protamine and AuNPs. Trypsin can easily hydrolyze protamine, leading to the quench of the fluorescence. Then, the fluorescence could be recovered again by the addition of parathion-methyl (PM) which could inhibit the activity of trypsin. By measuring the fluorescence of RF QDs, the inhibition efficiency of PM to trypsin activity was evaluated. Under the optimized conditions, the inhibition efficiency was proportional to the logarithm of PM concentration in the range of 0.04-400 ng mL(-1), with a detection limit of 0.018 ng mL(-1). Furthermore, the simple and convenient method had been used for PM detection in environmental and agricultural samples with satisfactory results. PMID- 26143469 TI - Multi-positively charged dendrimeric nanoparticles induced fluorescence quenching of graphene quantum dots for heparin and chondroitin sulfate detection. AB - A label-free fluorescence assay for rapid and sensitive detection of heparin (Hep) or chondroitin sulfate (CS) was developed by guanidine-terminated poly (amidoanime) (PAMAM-Gu(+)) dendrimers induced aggregation of graphene quantum dots (GQDs). The fluorescence of GQDs was obviously quenched after mixing with PAMAM-Gu(+). However, the addition of highly negatively charged Hep or CS into the fluorescence sensing system resulted in the fluorescence recovery. Because the multi-positively charged PAMAM-Gu(+) would prefer to bind with highly negatively charged Hep or CS, resulting in the deaggregation of GQDs. Under the optimized experimental conditions, the recovery of fluorescence intensity ratio I/I0 (I0 and I were the fluorescence intensity of the sensing system in the absence or presence of target analytes, respectively) was proportional to the concentration of target analytes in the range of 0.04-1.6 MUg mL(-1) for Hep and 0.1-2.5 MUg mL(-1) for CS. In addition, this method afforded high sensitivity with the detection limit as low as 0.02 MUg mL(-1) and 0.05 MUg mL(-1) for Hep and CS, respectively. All results suggested that the fluorescence turn-on method could be successfully employed for sensitive and selective detection of heparin analogs. PMID- 26143470 TI - Carbohydrate derivative-functionalized biosensing toward highly sensitive electrochemical detection of cell surface glycan expression as cancer biomarker. AB - Accurate and highly sensitive detection of glycan expression on cell surface is extremely important for cancer diagnosis and therapy. Herein, a carbohydrate derivative-functionalized biosensor was developed for electrochemical detection of the expression level of cell surface glycan (mannose used as model). Thiomannosyl dimer was synthesized to design the thiomannosyl-functionalized biosensor by direct and rapid one-step protocols. The biosensing surface-confined mannose could effectively mimic the presentation of cell surface mannose and was responsible for competing with mannose on cancer cells in incubation solution. Greatly enhanced sensitivity was achieved by exploiting the excellent conductivity of multiwalled carbon nanotube/Au nanoparticle (MWNT/AuNP), the amplification effect of MWNTs, and the favorable catalytic ability of horseradish peroxidase (HRP). Using competitive strategy, the developed biosensor exhibits attractive performances for the analysis of mannose expression with rapid response, high sensitivity and accuracy, and possesses great promise for evaluation of cell surface glycan expression by using a greater variety of lectins. PMID- 26143471 TI - Anton's syndrome with atypical presentation. PMID- 26143472 TI - Variability of ATP amount in last rinse water of automated washer-disinfectors demands monitoring of every load. PMID- 26143473 TI - Liver and spleen transient elastography and Acoustic Radiation Force Impulse Measurements. Performance and comparison of measurements in the same area concurrently assessed for liver fibrosis by biopsy. AB - PURPOSE: The estimation of the degree of liver fibrosis is important for prognosis, surveillance, and treatment of chronic liver disease. Although liver biopsy is the gold standard for diagnosis, it is subject to sampling error, while ultrasound-based techniques, such as Acoustic Radiation Force Impulse (ARFI) and transient elastography, have gained popularity. However, no previous comparative study has performed these ultrasound techniques at the time of biopsy. The aim of this study was to compare the reliability of these techniques to define the severity of liver fibrosis in viral hepatitis patients. PATIENTS AND METHODS: We compared liver transient elastography and Acoustic Radiation Force Impulse measurements, performed along the intended biopsy track, with liver biopsy results in 46 viral hepatitis patients, all measured on the same morning. Fibrosis was measured by histology using the Ishak fibrosis staging. RESULTS: The relative sensitivity and specificity of different incremental cut-off values for both techniques, and the predictive ability of pairwise comparison of the 3 tests (including APRI) and of their combined use with more severe grades of histology measured liver fibrosis, show that the single variable with greatest sensitivity and specificity is TE with a cut-off of >10.0. CONCLUSION: Transient elastography has a better performance than ARFI, which has a lower sensitivity, in the diagnosis of severe stages of fibrosis. Also ARFI of the spleen is correlated with Ishak fibrosis staging, and could be a possible additional tool for the diagnosis of liver fibrosis. PMID- 26143474 TI - Glycoprotein from street rabies virus BD06 induces early and robust immune responses when expressed from a non-replicative adenovirus recombinant. AB - The rabies virus (RABV) glycoprotein (G) is responsible for inducing neutralizing antibodies against rabies virus. Development of recombinant vaccines using the G genes from attenuated strains rather than street viruses is a regular practice. In contrast to this scenario, we generated three human adenovirus type 5 recombinants using the G genes from the vaccine strains SRV9 and Flury-LEP, and the street RABV strain BD06 (nrAd5-SRV9-G, nrAd5-Flury-LEP-G, and nrAd5-BD06-G). These recombinants were non-replicative, but could grow up to ~10(8) TCID50/ml in helper HEK293AD cells. Expression of the G protein was verified by immunostaining, quantitative PCR and cytometry. Animal experiments revealed that immunization with nrAd5-BD06-G can induce a higher seroconversion rate, a higher neutralizing antibody level, and a longer survival time after rabies virus challenge in mice when compared with the other two recombinants. Moreover, the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly higher in mice immunized with nrAd5-BD06-G, which might also contribute to the increased protection. These results show that the use of street RABV G for non-replicative systems may be an alternative for developing effective recombinant rabies vaccines. PMID- 26143475 TI - Becoming a mother-circuit plasticity underlying maternal behavior. AB - The transition to motherhood is a dramatic event during the lifetime of many animals. In mammals, motherhood is accompanied by hormonal changes in the brain that start during pregnancy, followed by experience dependent plasticity after parturition. Together, these changes prime the nervous system of the mother for efficient nurturing of her offspring. Recent work has described how neural circuits are modified during the transition to motherhood. Here we discuss changes in the auditory cortex during motherhood as a model for maternal plasticity in sensory systems. We compare classical plasticity paradigms with changes that arise naturally in mothers, highlighting current efforts to establish a mechanistic understanding of plasticity and its different components in the context of maternal behavior. PMID- 26143476 TI - Neurosurgical Injuries Caused by the 2011 Van Earthquake: The Experience at the Van Regional Training and Research Hospital. AB - BACKGROUND: On October 23, 2011, a devastating earthquake, magnitude 7.2 on the Richter Scale, jolted the province of Van in the east of Turkey and led to hundreds of casualties. OBJECTIVES: In this study, we aimed to present our clinical experience in the management of patients with cranial and spinal injuries who were admitted to the Van Regional Training and Research Hospital. METHODS: The retrospective study included 44 (77.2%) patients who were referred to the neurosurgery department after being diagnosed with spinal and cranial injuries due to earthquake at the emergency department between October 23 and 27, 2011. RESULTS: The patients comprised 32 male (72.7%) and 12 (27.3%) female patients with a mean age of 23.5 years. The injuries included scalp injury (n = 16), burst fracture (n=7), compression fracture (n=3), epidural hematoma (n=9), subdural hematoma (n=3), contusion (n=1), traumatic subarachnoid hemorrhage (n=2), depressed skull fracture (n=3), linear fracture (n=9), cervical fracture (n=2), and pneumocephalus (n=1). Most of the patients (90.9%) had isolated injuries and the others (9.1%) presented with combined cranial and spinal injuries. At discharge, the 3 patients with spinal fractures were paraplegic, and of the 2 patients who were operatively treated due to subdural hematoma, 1 was hemiparesic and the other was hemiplegic. No mortality occurred in our patients. CONCLUSIONS: The results of this study demonstrated that, in the aftermath of a natural disaster, conducting correct triage procedures and performing a prompt intervention with appropriate and qualified equipment play key roles in reducing morbidity and mortality. PMID- 26143477 TI - Liquid chromatography-mass spectrometry analysis of five bisphosphonates in equine urine and plasma. AB - Bisphosphonates are used in the management of skeletal disorder in humans and horses, with tiludronic acid being the first licensed veterinary medicine in the treatment of lameness associated with degenerative joint disease. Bisphosphonates are prohibited in horseracing according to Article 6 of the International Agreement on Breeding, Racing and Wagering (published by the International Federation of Horseracing Authorities). In order to control the use of bisphosphonates in equine sports, an effective method to detect the use of bisphosphonates is required. Bisphosphonates are difficult-to-detect drugs due to their hydrophilic properties. The complexity of equine matrices also added to their extraction difficulties. This study describes a method for the simultaneous detection of five bisphosphonates, namely alendronic acid, clodronic acid, ibandronic acid, risedronic acid and tiludronic acid, in equine urine and plasma. Bisphosphonates were first isolated from the sample matrices by solid-phase extractions, followed by methylation with trimethylsilyldiazomethane prior to liquid chromatography - tandem mass spectrometry analysis using selective reaction monitoring in the positive electrospray ionization mode. The five bisphosphonates could be detected at low ppb levels in 0.5mL equine plasma or urine with acceptable precision, fast instrumental turnaround time, and negligible matrix interferences. The method has also been applied to the excretion study of tiludronic acid in plasma and urine collected from a horse having been administered a single dose of tiludronic acid. The applicability and effectiveness of the method was demonstrated by the successful detection and confirmation of the presence of tiludronic acid in an overseas equine urine sample. To our knowledge, this is the first reported method in the successful screening and confirmation of five amino- and non-amino bisphosphonates in equine biological samples. PMID- 26143478 TI - Immune infiltrate in cancer. PMID- 26143479 TI - Reciprocal relationship between acute stress and acute fatigue in everyday life in a sample of university students. AB - We investigated whether stress may influence fatigue, or vice versa, as well as factors mediating this relationship. Fifty healthy participants (31 females, 23.6+/-3.2 years) completed up to 5 momentary assessments of stress and fatigue during 5 days of preparation for their final examinations (exam condition) and 5 days of a regular semester week (control condition). Sleep quality was measured by self-report at awakening. A sub-group of participants (n=25) also collected saliva samples. Fatigue was associated with concurrent stress, stress reported at the previous measurement point, and previous-day stress. However, momentary stress was also predicted by concurrent fatigue, fatigue at the previous time point, and previous-day fatigue. Sleep quality mediated the association between stress and next-day fatigue. Cortisol and alpha-amylase did not mediate the stress-fatigue relationship. In conclusion, there is a reciprocal stress-fatigue relationship. Both prevention and intervention programs should comprehensively cover how stress and fatigue might influence one another. PMID- 26143480 TI - (1)H, (15)N and (13)C backbone resonance assignments of the N-terminal, tandem KH domains of human hnRNP E1. AB - Heterogeneous nuclear ribonucleoproteins (hnRNPs) can be divided into subgroups based on their RNA-binding characteristics. One subgroup in mammalian cells are the Poly(C)-binding proteins (PCBPs) comprised of hnRNP K/J and hnRNP E1-4 [the latter also known as PCBP 1-4 or alpha-complex proteins (alpha-CP) 1-4]. Each subgroup member has three K homology (KH) nucleic acid-binding domains. Individual KH domains bind short single-stranded (ss), poly-pyrimidine-rich nucleic acid sequences with rather weak affinity. In this study, we report the (1)H, (13)C and (15)N backbone resonance assignments of the first and second KH domains of hnRNP E1, which plays a pivotal role in posttranscriptional and translational regulation of RNA targets. Our NMR assignments lay the foundation for a detailed investigation of the dynamic cooperation of the tandem KH1 and KH2 domains to bind nucleic acids. PMID- 26143481 TI - Recommendations for gross examination and sampling of surgical specimens of the spleen. AB - This review examines handling and processing of spleen biopsies and splenectomy specimens with the aim of providing the pathologist with guidance in optimizing examination and diagnosis of splenic disorders. It also offers recommendations as to relevant reporting factors in gross examination, which may guide diagnostic workup. The role of splenic needle biopsies is discussed. The International Spleen Consortium is a group dedicated to promoting education and research on the anatomy, physiology, and pathology of the spleen. In keeping with these goals, we have undertaken to provide guidelines for gross examination, sectioning, and sampling of spleen tissue to optimize diagnosis (Burke). The pathology of the spleen may be complicated in routine practice due to a number of factors. Among these are lack of familiarity with lesions, complex histopathology, mimicry within several types of lesions, and overall rarity. To optimize diagnosis, appropriate handling and processing of splenic tissue are crucial. The importance of complete and accurate clinical history cannot be overstated. In many cases, significant clinical history such as previous lymphoproliferative disorders, hematologic disorders, trauma, etc, can provide important information to guide the evaluation of spleen specimens. Clinical information helps plan for appropriate processing of the spleen specimen. The pathologist should encourage surgical colleagues, who typically provide the specimens, to include as much clinical information as possible. PMID- 26143482 TI - High resolution three dimensional intracranial arterial wall imaging at 3 T using T1 weighted SPACE. AB - OBJECTIVE: To study the effect of imaging parameters on the contrast of T1 weighted SPACE (Sampling Perfection with Application optimized Contrast using different angle Evolutions, a 3D TSE variant) at 3 T for high resolution imaging of intracranial plaques before contrast and with post-gadolinium induced enhancement, and evaluate its relevance to patients with intracranial atherosclerosis. MATERIALS AND METHODS: Optimized parameters giving good T1 contrast between intracranial vessel wall and cerebrospinal fluid within a specific scan time and reasonable coverage were found by simulation and validated in a healthy volunteer study. Based on the results, a clinical protocol covering the three major intracranial arteries (middle cerebral arteries, basilar arteries, and petrous internal carotid arteries) was developed. It was applied in ten patients diagnosed with intracranial arterial lesions. The accuracy of the technique in depicting vessel lumen was assessed by comparison to contrast enhanced MR angiography. The contrast enhancement ratios of the vessel wall/plaque identified were analyzed. RESULTS: Simulation and volunteer study showed that using T1 weighted SPACE, good T1 contrast between vessel wall and cerebrospinal fluid occurred at TR of around 1000 ms using an echo train length of 21 within 10 minutes at an isotropic spatial resolution of 0.5 mm. In the 10 patients, 24 plaques were identified in the various segments of the intracranial arterial system of which eight appeared normal on MR angiography. Post-contrast enhancement ratio of these plaques varied from 0% up to 156%. CONCLUSIONS: T1 weighted SPACE provides good T1 contrast between intracranial arterial wall and cerebrospinal fluid with high resolution and good coverage within a clinically acceptable scan time. It can depict plaques pre- and post-contrast along the vessels surrounded by cerebrospinal fluid in the intracranial arterial system, and would be a useful tool in the clinical assessment of intracranial arterial diseases. PMID- 26143483 TI - Functional disconnection between the visual cortex and the sensorimotor cortex suggests a potential mechanism for self-disorder in schizophrenia. AB - Self-disorder is a hallmark characteristic of schizophrenia. This deficit may stem from an inability to efficiently integrate multisensory bodily signals. Twenty-nine schizophrenia patients and thirty-one healthy controls underwent resting-state fMRI in this study. A data-driven method, functional connectivity density mapping (FCD), was used to investigate cortical functional connectivity changes in the patients. Areas with significantly different FCD were chosen to calculate functional connectivity maps. The schizophrenia patients exhibited increased local FCD in frontal areas while demonstrating decreased local FCD in the primary sensorimotor area and in the occipital lobe. The functional connectivity analysis illustrated decreased functional connectivity between visual areas and the primary sensorimotor area. These findings suggest disturbed integration in perception-motor processing, which may contribute to mapping the neural physiopathology associated with self-disorder in schizophrenia patients. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry. Registration number. ChiCTR-RCS-14004878. PMID- 26143484 TI - Diagnostic work-up and laparoscopic correction of an ectopic ureter. AB - INTRODUCTION: A duplex renal collecting system is a common congenital anomaly in children. Continuous dribbling (especially if after the toilet-training period) should raise suspicion of the presence of an ectopic ureter, which is most often associated with ureteral duplication. This video will demonstrate the complete diagnostic work-up necessary in these cases. CASE REPORT: A 10-year-old girl presented with continuous dribbling. Ultrasonography and computerized tomography depicted a duplex system on the left side, with the upper pole ureter ectopically inserting into the vaginal cavity and good upper pole renal parenchyma. A careful urethrocystoscopy showed a topic right ureteral orifice and a topic lower pole left ureteral orifice. Retrograde pyelography was performed and displayed normal left lower pole anatomy. A vaginography was performed, which showed reflux to the ectopic ureter. Vaginoscopy clearly identified the ectopic ureteral orifice. A guide wire was introduced through this meatus and retrograde contrast injection confirmed the diagnosis of an ectopic ureter. RESULTS: At laparoscopy, a larger upper pole ureter and a normal lower pole ureter on the left side were identified. A termino-lateral ureteroureteral anastomosis was performed. After the procedure, the child reported immediate resolution of urinary dribbling. CONCLUSION: In order to optimize its surgical correction, efforts should be made to appropriate localization of the ectopic ureter. PMID- 26143485 TI - Incontinence in persons with Noonan Syndrome. AB - OBJECTIVE: Noonan Syndrome (NS) is an autosomal neurodevelopmental disorder with a high phenotypic variability. Mutations in several genes of the RASMAPK signaling pathways are now known to be responsible for NS. Most of the children with NS are of average intelligence, one-third have a mild intellectual disability (ID) (IQ 50-79). So far, no studies have assessed incontinence in persons with NS. The aim of this study therefore was to investigate the prevalence of incontinence and psychological problems in persons with NS. SUBJECTS AND METHODS: Nineteen children (5-17 years) and 10 adults (18-48 years) with NS were recruited through a German parent support group (58.6% male, mean age 15.26 years). The "Parental Questionnaire: Enuresis/Urinary Incontinence", "Encopresis Questionnaire - Screening Version" and the German version of the International Consultation on Incontinence Questionnaire - Pediatric Lower Urinary Tract Symptom (ICIQ-CLUTS) were completed by parents or caregivers to assess incontinence and lower urinary tract symptoms (LUTS). The Developmental Behavior Checklist for parents (DBC-P) or the Developmental Behavior Checklist for adults (DBC-A) were filled out to assess psychological symptoms. RESULTS: In total, 27.3% of the children (4-12 years) had nocturnal enuresis (NE), 36.4% had daytime urinary incontinence (DUI), and 11.1% had fecal incontinence (FI). Only one adolescent (13-17 years) had NE (14.3%) and one young adult (18-30 years) had FI (11.1%); 36.4% of the children, 33.3% of the adolescents and 12.5% of young adults had a DBC score in the clinical range. No adult (>30 years) had incontinence or a critical DBC score. Children and adolescents with NE had significantly higher scores in the DBC total score as well in the "self-absorbed" and "social relating" subscales than continent children and adolescents, whereas no significant difference was found between children and adolescents with DUI compared with the continent group. CONCLUSIONS: A significant proportion of children with NS are affected by incontinence. Incontinence is a relevant problem in children and adolescents with NS, but does not persist into adulthood. In particular, psychological problems are present in children and adolescents with NE. Screening for both incontinence and psychological symptoms are recommended in children with NS. As most of the children with NS have average intelligence or a mild ID, they can be treated effectively with standard methods. PMID- 26143486 TI - Obesity, overweight, and eating problems in children with incontinence. AB - OBJECTIVE: The aim was to analyze the prevalence of eating problems and specific associations between overweight, obesity, and eating behavior in children with incontinence. SUBJECTS AND METHODS: Forty-three consecutively presented children with incontinence, diagnosed to International Children's Continence Society standards, and 44 matched continent controls were examined prospectively. All children received a physical examination, sonography, and a one-dimensional intelligence test. Child psychopathology was measured with the Child Behavior Checklist (CBCL/4-18). Eating problems were assessed with the German version of the Dutch Eating Behaviour Questionnaire for Children (DEBQ-C) and a 40-item parental questionnaire referring to atypical eating problems. RESULTS: Of the 43 children with incontinence, 23.3% had nocturnal enuresis (NE) only, 37.2% had any form of daytime urinary incontinence (DUI) (isolated or combined with NE) and 39.5% had fecal incontinence (FI) (isolated or combined with NE and/or DUI). Incontinent children showed significantly more CBCL externalizing symptoms (35.7% vs. 6.8%) and total problems (46.3% vs. 6.8%) in the clinical range (>90th percentile), as well as significantly lower mean IQ (105.5 vs. 120.6) than continent controls. Of the children with incontinence, 16.9% were affected by obesity (>=95th body mass index [BMI] percentile) compared with none of the continent controls. Especially in children with FI, the rate of obesity was significantly increased (23.5%). In addition, 46.5% of incontinent children, but none of the controls, had constipation. Again, children with FI (82.4%) had the highest rate of constipation (>DUI: 25% > NE only: 20%). "Food refusal" (FR) and "intense fear of gaining weight" (GW), but not other eating problems, were significantly more common among incontinent children (FR mean score 7.3; GW mean score 1.4) than in controls (FR mean score 5.6; GW mean score 0.7). After controlling for BMI percentiles, FR still was significantly higher in incontinent children. Children with FI had the highest score of FR among all subgroups of incontinence (mean score 9.1). CONCLUSIONS: This study shows that overweight, obesity, behavioral and eating problems are especially associated with disorders of the gastrointestinal tract (FI and constipation), and only to a lesser degree with those of the urinary tract (DUI and NE). These problems should be addressed routinely in the clinical care of children with incontinence. PMID- 26143487 TI - 27 years of experience with the comprehensive surgical treatment of prune belly syndrome. AB - INTRODUCTION: Prune belly syndrome (PBS) presents with three main features: abdominal wall flaccidity, urological abnormalities and cryptorchidism. As a result, urologists must consider the eventual repair of the abdominal wall flaccidity and urinary tract abnormalities, and the mandatory correction of cryptorchidism, as well as decide whether to perform the procedures in a single comprehensive approach or in multiple steps. OBJECTIVES: To report experiences with comprehensive surgical management of prune belly syndrome. MATERIAL AND METHODS: From 1987 to 2014, 46 children with PBS were submitted for comprehensive surgical treatment. According to individual needs, treatment aimed to correct the abdominal flaccidity, reconstruct the urinary tract, and perform bilateral orchiopexy and circumcision, which were performed in one procedure. Urinary tract reconstruction was indicated whenever pyelo-ureteral dilatation with evidence of significant stasis and/or vesicoureteral reflux was associated with recurrent urinary tract infections (UTI). Treatment for this cohort included: 44 abdominoplasties, 40 upper urinary tract reconstructions, 44 cystoplasties associated with three appendico-vesicostomies, 46 bilateral orchiopexies and 36 circumcisions. The median age at surgery was 16 months and children were followed for a median of 143 months. RESULTS: Abdominal appearance and tonus were improved in 90% of the children after the primary surgery and 100% after reoperation. Upper urinary tract reconstruction was performed in most children and long-term follow-up showed functional stabilization of the urinary tract in about 90% of the children, with progression to renal failure in 10%. Lower urinary tract reconstruction was performed in most children (95.6%); on late follow-up, continence was observed in 81% of them, while incontinence was present in 19% and usually associated with polyuria. Adequate bladder emptying was possible in most boys (82.6%), while the remaining required clean intermittent catheterization. Pre-operative UTI was present in 89.1% and urinary sepsis in 15.2%. Postoperatively, the incidence of laboratorial UTI was significantly reduced to 39.1%, while urinary sepsis was absent. Bilateral orchiopexy was performed in all children, with 85% of the testes becoming normal in size and well located in the scrotum. CONCLUSIONS: Comprehensive surgical treatment is feasible and has good long-term results. A considerable incidence of reoperations due to complications or progression of the disease was observed. The long-term results for reno ureteral anatomy and function, bladder function, infection, testicular size and location, as well as abdominal aspect and tonus, show that comprehensive surgery is an adequate method for managing children with PBS. PMID- 26143488 TI - A needs assessment of unused and expired medication disposal practices: A study from the Medication Safety Research Network of Indiana. AB - BACKGROUND: Access and availability of unused and expired medication (UEM) due to improper disposal and storage is a serious issue, potentially leading to abuse and environmental concerns. OBJECTIVE: To describe the extent of the UEM issue in Indiana (U.S. State), identify patient beliefs about UEM, and determine any association between those beliefs and various personal/demographic characteristics. RESULTS: A needs assessment was conducted among community pharmacy patients. A convenience sample of 200 patients from 15 community pharmacies that are part of a practice-based research network (PBRN) in Indiana completed a survey concerning UEM beliefs and behaviors from Feb-March, 2014. Approximately 40% of patients were aware of a UEM take-back location in their community, although only 15% had utilized a UEM take-back location. Seventy-seven percent of patients were willing to drive to a take-back location to return UEM. Particularly vulnerable populations lacking knowledge regarding UEM and access to proper disposal were identified. CONCLUSIONS: While states have made efforts to increase accessibility for UEM return, there remains a need for more disposal locations for both non-controlled and controlled medication. PMID- 26143489 TI - Integration of prescription drug monitoring programs (PDMP) in pharmacy practice: Improving clinical decision-making and supporting a pharmacist's professional judgment. AB - BACKGROUND: Pharmacists have shared responsibility to investigate the validity of controlled substance prescriptions (CSPs) that raise concerns, or red flags, and subsequently exercise their right to refuse to dispense a CSP if its validity cannot be verified. Improving access to clinical practice tools, such as prescription drug monitoring programs (PDMPs), may increase availability of a patient's drug history, which is critical to making informed clinical decisions about dispensing CSPs. OBJECTIVES: The purpose of this study was to examine how integration and consistent use of a PDMP in pharmacy practice impacts pharmacists' dispensing practices related to CSPs. METHODS: A cross-sectional study examined pharmacists' knowledge and use of Indiana's (US State) PDMP (INSPECT) and dispensing practices of CSPs. Three outcome measures were analyzed using multiple logistic regression so as to examine the relationship between PDMP use and pharmacists' controlled substance dispensing behaviors. RESULTS: Pharmacists were 6.4 times more likely to change their dispensing practice to dispense fewer CSPs if they reported that INSPECT provides increased access to patient information. Pharmacists who always use INSPECT refused an average of 25 CSPs annually compared to an average of 7 refusals for pharmacists not using INSPECT. Pharmacists using INSEPCT consistently (at every visit) were 3.3 times more likely to refuse to dispense more CSPs than pharmacists who report never using INSPECT. CONCLUSIONS: Integration of PDMPs in pharmacy practice may improve a pharmacist's ability to make informed clinical decisions and exercise sound professional judgment. Providing clinical practice tools to both prescribers and pharmacists is important to preventing drug diversion and prescription drug abuse. Future research should focus on understanding the barriers and challenges to successful integration of PDMPs in pharmacy practice. PMID- 26143490 TI - ATM in senescence. PMID- 26143491 TI - AMP-activated kinase (AMPK) regulates activity of HER2 and EGFR in breast cancer. AB - AMP-activated Protein Kinase (AMPK) activity retards growth of many types of cancers. Investigating effects of AMPK activation on breast cancer cell signaling and survival, we found that breast cancer cell lines with amplification and over expression of HER2 or EGFR are 2- to 5-fold more sensitive to cytotoxic effects of AICAR, a canonical pharmacological activator of AMPK, than breast cancer cell lines lacking HER2 or EGFR overexpression. Paralleling effects on cell survival, AICAR leads to dose- and time-dependent inhibition of HER2 and EGFR in HER2 amplified breast cancer cells, with activation of AMPK and suppression of HER2/ EGFR activity preceding commitment to cell death. Transfection of constitutively active AMPKalpha also leads to decreased HER2 and EGFR phosphorylation, reduced downstream signaling associated with these receptor tyrosine kinases (RTKs), and reduced breast cancer cell growth, confirming effects of AMPK activity on HER2/ EGFR. Ensuing co-immunoprecipitation experiments demonstrated an interaction of HER2 with AMPK and an in vitro phosphorylation assay found that HER2 and EGFR contain sequences that are potential substrates for AMPK. Our results lead us to postulate that AMPK regulates HER2 and EGFR activity in HER2-amplified breast cancer cells and thus activation of AMPK might provide therapeutic benefit in such cancers. PMID- 26143493 TI - The Healthy Immigrant Effect on Mental Health: Determinants and Implications for Mental Health Policy in Spain. AB - Since the mid-1990s, Spain has started to receive a great number of migrant populations. The migration process can have a significantly negative impact on mental health of immigrant population and, consequently, generate implications for the delivery of mental health services. The aim of this article is to provide empirical evidence to demonstrate that the mental health of immigrants in Spain deteriorates the longer they are resident in the country. An empirical approach to this relationship is carried out with data from the National Survey of Health of Spain 2011-2012 and poisson and negative binomial models. Results show that immigrants who reside <10 years in Spain appear to be in a better state of mental health than that observed for the national population. Studying health disparities in the foreign population and its evolution are relevant to ensure the population's access to health services and care. The need for further research is especially true in the case of the immigrant population's mental health in Spain because there is scant evidence available on their situation. PMID- 26143492 TI - Aqueous Extracts of Hibiscus sabdariffa Calyces Decrease Hepatitis A Virus and Human Norovirus Surrogate Titers. AB - Hibiscus sabdariffa extract is known to have antioxidant, anti-diabetic, and antimicrobial properties. However, their effects against foodborne viruses are currently unknown. The objective of this study was to determine the antiviral effects of aqueous extracts of H. sabdariffa against human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) and hepatitis A virus (HAV) at 37 degrees C over 24 h. Individual viruses (~5 log PFU/ml) were incubated with 40 or 100 mg/ml of aqueous hibiscus extract (HE; pH 3.6), protocatechuic acid (PCA; 3 or 6 mg/ml, pH 3.6), ferulic acid (FA; 0.5 or 1 mg/ml; pH 4.0), malic acid (10 mM; pH 3.0), or phosphate buffered saline (pH 7.2 as control) at 37 degrees C over 24 h. Each treatment was replicated thrice and plaque assayed in duplicate. FCV-F9 titers were reduced to undetectable levels after 15 min with both 40 and 100 mg/ml HE. MNV-1 was reduced by 1.77 +/- 0.10 and 1.88 +/- 0.12 log PFU/ml after 6 h with 40 and 100 mg/ml HE, respectively, and to undetectable levels after 24 h by both concentrations. HAV was reduced to undetectable levels by both HE concentrations after 24 h. PCA at 3 mg/ml reduced FCV-F9 titers to undetectable levels after 6 h, MNV-1 by 0.53 +/- 0.01 log PFU/ml after 6 h, and caused no significant change in HAV titers. FA reduced FCV-F9 to undetectable levels after 3 h and MNV-1 and HAV after 24 h. Transmission electron microscopy showed no conclusive results. The findings suggest that H. sabdariffa extracts have potential to prevent foodborne viral transmission. PMID- 26143494 TI - Estradiol protects female rats against sepsis induced by Enterococcus faecalis improving leukocyte bactericidal activity. AB - Enterococcus faecalis is a Gram-positive bacteria described as an important causative agent of sepsis. The contact between host leukocytes and bacteria activates the innate immunity, participating as the first defense mechanism against infection. Pro-inflammatory cytokines [including tumor necrosis factor (TNF)-alpha and interleukin-1beta] and nitric oxide (NO) are essential to recruitment of leukocytes into the infectious focus as well as their activation for phagocytosis. Beyond the bacteria species, gender has been considered another factor to predict outcome in septic patients. Studies suggest that females exhibit a protective advantage during sepsis models, being gonadal hormones possible modulators of functions of immune cells. Nevertheless, the role of estradiol during Gram-positive infection remains a literature gap. Our aims were to investigate whether estradiol protects rats against bacterial dissemination during E. faecalis-induced sepsis. We determined whether estradiol modulates the local and systemic inflammatory response, as well as the cell migration into the infectious focus and the bactericidal capacity of leukocytes. Our findings demonstrated that estradiol pre-treated rats showed a dose-dependent reduction in bacterial counts in peritoneal lavage fluid (PLF) and in liver. Moreover, TNF alpha and nitrate levels were increased in plasma, while only TNF-alpha was increased in the PLF in estradiol-treated rats. The prevention of bacterial dissemination may be related to the enhanced neutrophil and macrophage migration into the peritoneal cavity. Furthermore, estradiol improved the phagocytic and bactericidal ability of these both inflammatory cells. Taken together, the present study clearly demonstrates an important protective role of estradiol against sepsis induced by E. faecalis in female rats. PMID- 26143496 TI - Semiotic individuation and Ernst Cassirer's challenge. AB - The concept of individuation has suffered from its being mostly connected with Jungian psychology or nominalist philosophy. In this paper, "individuation" will be understood rather as a process; and in particular, as a series of stages (morphological and/or cognitive) that an organism passes through during its lifespan. In most species, individuation is restricted to a short period in early life, as when birds acquire their species specific songs; while in humans - and a few other species of birds or mammals (although to a much lesser degree) - individuation is a life-long, open-ended process. In this understanding, individuation becomes narrowly connected to learning. And since learning necessarily depends on what is already learned, the trajectory of learning-based individuation is necessarily indefinite and dependent on the concrete chance events and steps whereby the process has proceeded. Semiotic individuation is a historical process, and this fact explains why systems biology, as established by Ludwig van Bertalanffy, has not been capable of meeting the hope, expressed long ago by Ernst Cassirer, of bridging the mechanicist-vitalist gap in biology. Instead, a semiotic approach is called for. Human individuation, moreover, is special in a very important sense: language use implies that humans from earliest childhood inescapably become entangled in an 'as-if-world', a virtual reality, a story about who we are and how our life 'here and now' belongs within our own life-history, as well as within the greater pattern of the world around us. Human individuation is thus a double-tracked process, consisting in an incessant reconciliation or negotiation between the virtual reality that we have constructed in our minds and mind-independent reality as it impresses itself upon our lives. Human life cannot therefore be defined by its uniqueness as a particular genetic combination, but must be instead be defined by its uniqueness as a temporal outcome of semiotic individuation. Accordingly, this double-tracked character of human semiotic individuation implies that it is cast as just one particular outcome of a combinatorics with an infinite number of possible outcomes. It is suggested here that our ingrained feeling of possessing a free will is buried in this fact. PMID- 26143495 TI - Performance of a quality assurance program for assessing dental health in methamphetamine users. AB - BACKGROUND: Systematic characterization of the dental consequences of methamphetamine (MA) abuse presupposes a rigorous quality assurance (QA) program to ensure the credibility of the data collected and the scientific integrity and validity of the clinical study. In this report we describe and evaluate the performance of a quality assurance program implemented in a large cross-sectional study of the dental consequences of MA use. METHODS: A large community sample of MA users was recruited over a 30 month period during 2011-13 and received comprehensive oral examinations and psychosocial assessments by site examiners based at two large community health centers in Los Angeles. National Health and Nutrition Examination Survey (NHANES) protocols for oral health assessments were utilized to characterize dental disease. Using NHANES oral health quality assurance guidelines, examiner reliability statistics such as Cohen's Kappa coefficients and inter-class correlation coefficients were calculated to assess the magnitude of agreement between the site examiners and a reference examiner to ensure conformance and comparability with NHANES practices. RESULTS: Approximately 9% (n = 49) of the enrolled 574 MA users received a repeat dental caries and periodontal examination conducted by the reference examiner. There was high concordance between the reference examiner and the site examiners for identification of untreated dental disease (Kappa statistic values: 0.57-0.75, percent agreement 83-88%). For identification of untreated caries on at least 5 surfaces of anterior teeth, the Kappas ranged from 0.77 to 0.87, and percent agreement from 94 to 97%. The intra-class coefficients (ICCs) ranged from 0.87 to 89 for attachment loss across all periodontal sites assessed and the ICCs ranged from 0.79 to 0.81 for pocket depth. For overall gingival recession, the ICCs ranged from 0.88 to 0.91. When Kappa was calculated based on the CDC/AAP case definitions for severe periodontitis, inter-examiner reliability for site examiners was low (Kappa 0.27-0.67). CONCLUSION: Overall, the quality assurance program confirmed the procedural adherence of the quality of the data collected on the distribution of dental caries and periodontal disease in MA-users. Examiner concordance was higher for dental caries but lower for specific periodontal assessments. PMID- 26143497 TI - Coinfection with Fusobacterium nucleatum can enhance the attachment and invasion of Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans to human gingival epithelial cells. AB - OBJECTIVE: This study was conducted to investigate effects of coinfection of Porphyromonas gingivalis (P. gingivalis) or Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) with Fusobacterium nucleatum (F. nucleatum) on their adhering and invasive capacity to human gingival epithelial cells as well as the expression of interleukin-8 (IL-8) and human beta-defensin-2 (hBD-2) in human gingival epithelial cells. DESIGN: P. gingivalis and A. actinomycetemcomitans were tested for their ability to attach and invade a human gingival epithelial cell line (Ca9-22) alone or coinfecting with F. nucleatum. Also, expression levels of IL-8 and hBD-2 were detected respectively using enzyme linked immunosorbent assay (ELISA) and real-time reverse transcription PCR (RT-PCR) when Ca9-22 cells were infected with P. gingivalis and A. actinomycetemcomitans alone or coinfecting with F. nucleatum. RESULTS: F. nucleatum, P. gingivalis and A. actinomycetemcomitans were allowed to adhere and invade Ca9-22 cells, either each strain alone or under coinfection. The adhering and invasive abilities of P. gingivalis and A. actinomycetemcomitans were significantly greater when they were coincubated with F. nucleatum (P<0.05) than either of them alone. These enhancements were inhibited by galactose. In addition, P. gingivalis and A. actinomycetemcomitans inhibited the activation of IL-8 and hBD-2 by F. nucleatum. Also, galactose disrupted this inhibition on the expression of IL-8 and hBD-2. CONCLUSION: These results suggested coinfection with F. nucleatum can enhance adhesion and invasion of P. gingivalis and A. actinomycetemcomitans to Ca9-22 cells, as well as inhibition on host innate immune response. PMID- 26143498 TI - Applying chemical genetic tools to the study of phospho-signalling pathways in malaria parasites. AB - Until very recently there has been very little information about the phospho signalling pathways in apicomplexan parasites including the most virulent species of human malaria parasite, Plasmodium falciparum. With the advancement of mass spectrometry-based phosphoproteomics and the development of chemical genetic approaches to target specific parasite protein kinases, the complexity of the essential role played by phosphorylation in maintaining the viability of apicomplexan parasites is now being revealed. This review will describe these recent advances and will discuss how these approaches can be used to validate parasite protein kinases as drug targets and to determine the on- and off-target action of protein kinase inhibitors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. PMID- 26143499 TI - In infancy the timing of emergence of the other-race effect is dependent on face gender. AB - Poorer recognition of other-race faces relative to own-race faces is well documented from late infancy to adulthood. Research has revealed an increase in the other-race effect (ORE) during the first year of life, but there is some disagreement regarding the age at which it emerges. Using cropped faces to eliminate discrimination based on external features, visual paired comparison and spontaneous visual preference measures were used to investigate the relationship between ORE and face gender at 3-4 and 8-9 months. Caucasian-White 3- to 4-month olds' discrimination of Chinese, Malay, and Caucasian-White faces showed an own race advantage for female faces alone whereas at 8-9 months the own-race advantage was general across gender. This developmental effect is accompanied by a preference for female over male faces at 4 months and no gender preference at 9 months. The pattern of recognition advantage and preference suggests that there is a shift from a female-based own-race recognition advantage to a general own race recognition advantage, in keeping with a visual and social experience-based account of ORE. PMID- 26143500 TI - Removal of ammonium from swine wastewater by zeolite combined with chlorination for regeneration. AB - This study investigated a process using ammonium ion (NH4(+)) exchange on zeolite in combination with chlorination regeneration for the safe treatment of simulated swine wastewater. Two stages i) 120-min zeolite ion-exchange and ii) 10-min exchanged zeolite regeneration facilitated NH4(+) ion removal from wastewater. Solution pH, contact time, adsorbent dosage, and competitive cations were the significant factors influencing the entire process. The effect of competitive cations on NH4(+) removal effectively followed the order of preference as Na(+)>K(+)>Ca(2+)>Mg(2+) at equivalent concentrations. The chlorination method experimentally removed approximately 99% of the NH4(+) exchanged on the zeolite, without remaining NH4(+) in the regeneration solution. Our analysis revealed that, in this process, the NH4(+) exchanged on the zeolite was first replaced by Na(+) and then oxidized to nitrogen gas. Reuse of the regenerated zeolite (GZ) indicated that the removal efficiency of NH4(+) ions was equal to that of the fresh zeolite modified with NaCl. Results of kinetic analysis revealed that the NH4(+) exchange on the GZ followed the pseudo-second-order model and the intraparticle diffusion model only for the first 60 min. The ion-exchange isotherm results demonstrated that the Langmuir model provided a slightly more consistent fit to the equilibrium data as compared with the Freundlich model. Repetitive experimental results confirmed that the proposed zeolite recycling process was stable and usable in simulated swine wastewater treatment. PMID- 26143501 TI - Is biosorption suitable for decontamination of metal-bearing wastewaters? A critical review on the state-of-the-art of biosorption processes and future directions. AB - For the past few decades, biosorption has been widely investigated for the removal of different contaminants in aqueous media. A number of biomasses of different genre have been identified to possess good biosorption capacity. Insights into biosorption mechanisms have been provided by various researchers in order to develop a fundamental scientific understanding of the biosorption process. However, biosorption has not been employed widely for its large-scale commercial applications. The key factors that affect the growth and evolution of biosorption as a practical technology for decontamination of wastewaters include, (1) lack of investigations on multi-component solutions and wastewaters with complex matrix effects, (2) incomplete understanding of physico-chemical characteristics of biomasses of different types, (3) lack of studies to improve the performance of biosorbents through surface functionalization, and (4) non integration of biosorption in wastewater/water treatment plants. This critical review aims to identify and discuss the practical limitations of biosorption and provide future research directions to make biosorption a technologically viable process with emphasis on selection and modification of biomasses to suit desired treatment applications, identify appropriate operation modes for large-scale applications of biosorption, and perform techno-economic evaluation of overall biosorption processes. PMID- 26143503 TI - Hot Topics: Electrical Injuries in the Emergency Department. PMID- 26143502 TI - Inducible release of particulates from liposomes using the mechanosensitive channel of large conductance and L-alpha-lysophosphatidylcholine. AB - The mechanosensitive channel of large conductance (MscL) from Escherichia coli is a prototype for the mechanosensitive class of ion channels and opens one of the largest known gated transmembrane pores. As such, MscL offers the structural framework for the development of liposomal nanovalves for biotechnological applications. Here we incorporated MscL into liposomes and investigated the effects of L-alpha-lysophosphatidylcholine (LPC) with varying acyl chain lengths or saturation on its pore gating. This was measured by the efflux of encapsulated 5,6-carboxyfluorescein (CF) from the MscL proteoliposomes. Efflux improved in the presence of shorter and double-bonded LPC acyl chains. It was also dependent on the detergent concentration employed during MscL purification. MscL purified in 2 mM dodecyl beta-D-maltopyranoside (DDM) had a marked increase in CF efflux compared to MscL purified in 1 mM DDM when treated with LPC. The purification conditions also resulted in increased efflux from proteoliposomes containing the G22C-MscL pore mutant channel, which requires higher membrane tension for its activation compared to WT-MscL. PMID- 26143504 TI - Situation, Background, Assessment, and Recommendation-Guided Huddles Improve Communication and Teamwork in the Emergency Department. AB - PROBLEM: Thousands of people die annually in hospitals because of poor communication and teamwork between health care team members. Standardized tools and strategies help increase the amount and quality of communication. Two structured communication methods include implementing huddles and the use of the situation, background, assessment, and recommendation (SBAR) communication framework. METHODS: To improve communication among nurse practitioners and registered nurses within a pediatric emergency department, a performance improvement project with the structured processes of a joint patient evaluation and huddle was implemented. Data were gathered from 32 nurses and 2 nurse practitioners using structured observation and pre- and post-implementation surveys. The following outcomes were measured: presence or absence of joint patient evaluation and SBAR-guided huddle, verbalization of treatment plan, communication, teamwork, and nurse satisfaction. RESULTS: Eighty-three percent of patient encounters included a joint evaluation. A huddle structured with SBAR was conducted 86% of the time. Registered nurses and nurse practitioners verbalized patients' treatment plans in 89% of cases and 97% of cases, respectively. Improved teamwork, communication, and nursing satisfaction scores were demonstrated among the nurse practitioners and registered nurses. IMPLICATIONS FOR PRACTICE: This project showed the feasibility of a simple and inexpensive joint nurse practitioner-registered nurse patient evaluation followed by a structured huddle, which improved communication, teamwork, and nurse satisfaction scores. This performance-improvement project has the potential to enhance efficiency by reducing redundancy, as well as to improve patient safety through the use of structured communication techniques. PMID- 26143505 TI - Frame-difference analysis of video-recorded laser-beam projections. AB - Laser beams have been applied in many human motion research contexts to project movements in specific motor tasks. Currently, there are no objective analysis methods for laser projection recordings. The principal aim of this study was to investigate the feasibility of quantifying motion by applying frame differencing and image analysis methods to video streams of laser beam projections. The laser projection was controlled by a mechanical device that produced pseudo random rotations. The 2D motion recorded by the video was compared with recordings obtained with an electromagnetic system where a sensor was fixed to the same device as the laser. High correlations in the time and frequency domains were found between the methods. We conclude that the proposed method can accurately quantify complex motion patterns from laser beam projections. PMID- 26143506 TI - Editorial. PMID- 26143507 TI - Octadecaneuropeptide ODN prevents hydrogen peroxide-induced oxidative damage of biomolecules in cultured rat astrocytes. AB - Oxidative stress, associated with a variety of disorders including neurodegenerative diseases, is a major cause of cellular dysfunction and biomolecule damages which play a crucial role in neuronal apoptosis. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide ODN. We have recently shown that ODN is a potent glioprotective agent that prevents hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis. The purpose of the present study was to investigate the potential protective effect of ODN on oxidative-generated damage of biomolecules in cultured rat astrocytes. Incubation of cells with subnanomolar concentrations of ODN (0.1fM-0.1nM) inhibited H2O2-evoked reactive oxygen species accumulation and cell death in a concentration-dependent manner. Exposure of H2O2 treated cells to 0.1nM ODN inhibited superoxide anion generation and blocked oxidative damage of cell molecules caused by H2O2i.e. formation and accumulation of lipid oxidation products, malondialdehydes and conjugated dienes, and protein carbonyl compounds. Taken together, these data demonstrate for the first time that ODN prevents oxidative stress-induced alteration of cellular constituents. ODN is thus a potential candidate to reduce neuronal damage in various pathological conditions involving oxidative neurodegeneration. PMID- 26143508 TI - The use of a prescription drug monitoring program to develop algorithms to identify providers with unusual prescribing practices for controlled substances. AB - The misuse, abuse and diversion of controlled substances have reached epidemic proportion in the United States. Contributing to this problem are providers who over-prescribe these substances. Using one state's prescription drug monitoring program, we describe a series of metrics we developed to identify providers manifesting unusual and uncustomary prescribing practices. We then present the results of a preliminary effort to assess the concurrent validity of these algorithms, using death records from the state's vital records database pertaining to providers who wrote prescriptions to patients who then died of a medication or drug overdose within 30 days. Metrics manifesting the strongest concurrent validity with providers identified from these records related to those who co-prescribed benzodiazepines (e.g., valium) and high levels of opioid analgesics (e.g., oxycodone), as well as those who wrote temporally overlapping prescriptions. We conclude with a discussion of a variety of uses to which these metrics may be put, as well as problems and opportunities related to their use. PMID- 26143509 TI - Intelligence and handedness: Meta-analyses of studies on intellectually disabled, typically developing, and gifted individuals. AB - Understanding the relationship between cerebral laterality and intelligence is important in elucidating the neurological underpinnings of individual differences in cognitive abilities. A widely used, behavioral indicator for cerebral laterality, mainly of language, is handedness. A number of studies have compared cognitive abilities between groups of left- and right-handers, while others have investigated the handedness prevalence between groups of different cognitive abilities. The present study comprises five meta-analyses of studies that have assessed the handedness prevalence in (a) individuals with intellectual disability (ID) of unknown/idiopathic nature compared to typically developing (TD) individuals, and (b) individuals with intellectual giftedness (IG) compared to TD individuals. Nineteen data sets totaling 16,076 participants (5795 ID, 8312 TD, and 1969 IG) were included in the analyses. Elevated levels of atypical handedness were found to be robust only for the ID to TD comparison. Findings constrain the range of acceptable theories on the handedness distribution for different intelligence levels. PMID- 26143510 TI - Response to the input from the Reviewers. PMID- 26143511 TI - A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders. AB - Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of neuron and oligodendrocyte survival, neurite extension, axon regeneration, oligodendrocyte differentiation, axonal myelination and functional recovery; all processes highly implicated in numerous brain related functions. Although playing a major role in developmental brain functions, the potential application of Lingo-1 as a therapeutic target for the treatment of neurological disorders has so far been under-estimated. A number of preclinical studies have shown that various methods of antagonizing Lingo-1 results in neuronal and oligodendroglial survival, axonal growth and remyelination; however to date literature has only detailed applications of Lingo 1 targeted therapeutics with a focus primarily on myelination disorders such as multiple sclerosis and spinal cord injury; omitting important information regarding Lingo-1 signaling co-factors. Here, we provide for the first time a complete and thorough review of the implications of Lingo-1 signaling in a wide range of neurological and psychiatric disorders, and critically examine its potential as a novel therapeutic target for these disorders. PMID- 26143513 TI - Neuroprotection elicited by nerve growth factor and brain-derived neurotrophic factor released from astrocytes in response to methylmercury. AB - The protective roles of astrocytes in neurotoxicity induced by environmental chemicals, such as methylmercury (MeHg), are largely unknown. We found that conditioned medium of MeHg-treated astrocytes (MCM) attenuated neuronal cell death induced by MeHg, suggesting that astrocytes-released factors can protect neuronal cells. The increased expression of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) was observed in MeHg-treated astrocytes. NGF and BDNF were detected in culture media as homodimers, which are able to bind specific tyrosine kinase receptors, tropomyosin related kinase (Trk) A and TrkB, respectively. The TrkA antagonist and TrkB antagonist abolished the protective effects of MCM in neuronal cell death induced by MeHg. Taken together, astrocytes synthesize and release NGF and BDNF in response to MeHg to protect neurons from MeHg toxicity. This study is considered to show a novel defense mechanism against MeHg-induced neurotoxicity. PMID- 26143512 TI - NR2B subunit in the prefrontal cortex: A double-edged sword for working memory function and psychiatric disorders. AB - The prefrontal cortex (PFC) is a brain region featured with working memory function. The exact mechanism of how working memory operates within the PFC circuitry is unknown, but persistent neuronal firing recorded from prefrontal neurons during a working memory task is proposed to be the neural correlate of this mnemonic encoding. The PFC appears to be specialized for sustaining persistent firing, with N-methyl-D-aspartate (NMDA) receptors, especially slow decay NR2B subunits, playing an essential role in the maintenance of sustained activity and normal working memory function. However, the NR2B subunit serves as a double-edged sword for PFC function. Because of its slow kinetics, NR2B endows the PFC with not only "neural psychic" properties, but also susceptibilities for neuroexcitotoxicity and psychiatric disorders. This review aims to clarify the interplay among working memory, the PFC, and NMDA receptors; demonstrate the importance of NR2B in the maintenance of persistent activity; understand the risks and vulnerabilities of how NR2B is related to the development of neuropsychiatric disorders; identify gaps that currently exist in our understanding of these processes; and provide insights regarding future directions that may clarify these issues. We conclude that the PFC is a specialized brain region with distinct delayed maturation, unique neuronal circuitry, and characteristic NMDA receptor function. The unique properties and development of NMDA receptors, especially enrichment of NR2B subunits, endow the PFC with not only the capability to generate sustained activity for working memory, but also serves as a major vulnerability to environmental insults and risk factors for psychiatric disorders. PMID- 26143514 TI - Comparative effects of fipronil and its metabolites sulfone and desulfinyl on the isolated rat liver mitochondria. AB - Fipronil is an insecticide extensively used to control pests in crops and animals. There are relates of poisoning due to exposure of fipronil in mammals and the liver has been suggested as potential target. In this study, we evaluated the effects of fipronil and its metabolites sulfone and desulfinyl on the bioenergetics, reactive oxygen species (ROS) production and calcium efflux from mitochondria isolated from rat liver. Fipronil (5-25 MUM) inhibited state-3 respiration in mitochondria energized with glutamate plus malate, substrates of complex I of the respiratory chain and decreased the mitochondrial membrane potential resulting in inhibition of ATP synthesis. Fipronil also caused uncoupling in succinate-energized mitochondria and calcium efflux. The metabolites sulfone and desulfinyl also acted as mitochondrial inhibitors and uncouplers and caused calcium efflux, but with different potencies, being the sulfone the more potent one. These effects of fipronil and its metabolites on mitochondrial bioenergetics and calcium homeostasis may be related to toxic effects of the insecticide in the liver. PMID- 26143515 TI - Residents as Educators: A Modern Model. AB - Education during surgical residency has changed significantly. As part of the shifting landscape, the importance of an organized and structured curriculum has increased. However, establishing this is often difficult secondary to clinical demands and pressure both on faculty and residents. We present a peer-assisted learning model for academic institutions without professional non-clinical educations. The "resident as educator" (RAE) model empowers residents to be the organizers of the education curriculum. RAE is built on a culture of commitment to education, skill development and team building, allowing the upper level residents to develop and execute the curriculum. Several modules designed to address junior level residents and medical students' educational needs have been implemented, including (1) intern boot camp, (2) summer school, (3) technical skill sessions, (4) trauma orientation, (5) weekly teaching conferences, and (4) a fourth year medical student surgical preparation course. Promoting residents as educators leads to an overall benefit for the program by being cost-effective and time-efficient, while simultaneously promoting professional development of residents and a culture of education. PMID- 26143516 TI - Surgery and Medicine Residents' Perspectives of Morbidity and Mortality Conference: An Interdisciplinary Approach to Improve ACGME Core Competency Compliance. AB - OBJECTIVE: Morbidity and mortality conferences (MMCs) are often used to fulfill the Accreditation Council for Graduate Medical Education practice-based learning and improvement (PBLI) competency, but there is variation among institutions and disciplines in their approach to MMCs. The objective of this study is to examine the trainees' perspective and experience with MMCs and adverse patient event (APE) reporting across disciplines to help guide the future implementation of an institution-wide, workflow-embedded, quality improvement (QI) program for PBLI. DESIGN: Between April 1, 2013, and May 8, 2013, surgical and medical residents were given a confidential survey about APE reporting practices and experience with and attitudes toward MMCs and other QI/patient safety initiatives. Descriptive statistics and univariate analyses using the chi-square test for independence were calculated for all variables. Logistic regression and ordered logistic regression were used for nominal and ordinal categorical dependent variables, respectively, to calculate odds of reporting APEs. Qualitative content analysis was used to code free-text responses. SETTING: A large, multihospital, tertiary academic training program in the Pacific Northwest. PARTICIPANTS: Residents in all years of training from the Accreditation Council for Graduate Medical Education-accredited programs in surgery and internal medicine. RESULTS: Survey response rate was 46.2% (126/273). Although most respondents agreed or strongly agreed that knowledge of and involvement in QI/patient safety activities was important to their training (88.1%) and future career (91.3%), only 10.3% regularly or frequently reported APEs to the institution's established electronic incident reporting system. Senior-level residents in both surgery and medicine were more likely to report APEs than more junior-level residents were (odds ratio = 4.8, 95% CI: 3.1-7.5). Surgery residents had a 4.9 (95% CI: 2.3-10.5) times higher odds than medicine residents had to have reported an APE to their MMC or service, and a 2.5 (95% CI: 1.0-6.2) times higher odds to have ever reported an APE through any mechanism. The most commonly cited reason for not reporting APEs was "finding the reporting process cumbersome." Overall, 87% of respondents agreed or strongly agreed that MMCs were valuable, educational, and contributed to improving patient outcomes, but many cited opportunities for improvement. CONCLUSIONS: Although the perceived value of MMCs is high among both surgical and medicine trainees, there is significant variability across disciplines and level of training in APE reporting and experience with MMCs. This study presents a multidisciplinary resident perspective on optimizing APE reporting, MMCs, and PBLI compliance. PMID- 26143517 TI - Survey on Barriers to Adoption of Laparoscopic Surgery. AB - OBJECTIVE: To identify challenges that impede wider adoption of laparoscopy in gynecologic surgery and assessing whether the current training programs are addressing these challenges adequately. METHODS: A survey was designed to examine barriers to adoption of laparoscopy for practicing gynecologists. The survey was piloted on gynecologic surgeons and was further refined following their feedback. Finally, the survey was deployed to 4273 gynecologists across the United States via e-mail using the national database of the American Medical Association. Respondents were grouped into two categories based on how often they report referral of patients for laparoscopy. Demographics, training, and practice characteristics were compared using Fisher exact tests for categorical variables and t tests for continuous variables. Participants rated factors that were thought to limit laparoscopy use on a 5-point Likert scale; median values of these scores were compared with Wilcoxon rank sum tests. RESULTS: We received 210 responses (29% of people who opened the e-mail and 93% of those who opened the survey). Physicians who perform their own laparoscopies were on average younger and tended to be more subspecialized. Some of the most highly rated limiting factors included lack of adequate surgical volume, reluctance of managing unexpected surgical scenarios, difficulty with video-eye-hand coordination, altered depth perception, and laparoscopic suturing. CONCLUSION: This survey identified barriers to adoption of laparoscopic surgical techniques beyond what has previously been identified. Based on these findings, novel simulation and continuing medical education curricula can be created to address the primary barriers in order to increase laparoscopic approach to surgery among gynecologists. PMID- 26143518 TI - Factors and Influences That Determine the Choices of Surgery Residency Applicants. AB - OBJECTIVE: We sought to evaluate characteristics of residency applicants selected to interview at independent general surgery programs, identify residency information resources, assess if there is perceived bias toward university or independent programs, and determine what types of programs applicants prefer. STUDY DESIGN: An electronic survey was sent to applicants who were selected to interview at a participating independent program. Open-ended responses regarding reasons for program-type bias were submitted. Multivariable logistic regression models were estimated to identify applicant characteristics associated with program-type preference. SETTING: Independent general surgery residency programs. PARTICIPANTS: A total, of 1220 applicants were selected to interview at one of 33 independent programs. RESULTS: In total, 670 surveys were completed (55% response rate). Demographics of respondents were similar to the full invited population. Median United States Medical Licensing Examination Step 1 and Step 2 scores were between 230 to 239 and 240 to 249, respectively. Most applicants reported receiving general information about surgery residency programs and specific information about independent programs from residency program websites. 34% of respondents perceived an imbalanced representation of program types, with 96% of those reporting bias toward university programs. CONCLUSIONS: Applicants selected to interview at independent programs are competitive for general surgery training and primarily use residency program websites for information gathering. Bias is common toward university programs for a variety of perceived reasons. This information will be useful in applicant evaluation and selection, serve as a stimulus to update program websites, and challenge independent program directors to work to alleviate bias against their programs. PMID- 26143519 TI - Assessment of the Mexican Board of Pediatric Surgery Certification System. AB - OBJECTIVE: To evaluate the quality of the Mexican Board of Pediatric Surgery (MBPS) certifying system, using contemporary international guidelines. DESIGN: Retrospective assessment of evidence collected during the design and implementation processes of 2 consecutive applications of the MBPS certifying examination, using Cizek's checklist for evaluating credential-testing programs. It includes the relevant guidelines from the American Education Research Association, the American Psychological Association, the National Council on Measurement in Education, and the National Commission for Certifying Agencies. Four independent and previously trained raters used the checklist. They underwent a 2-week training using frame-of-reference and performance dimensions methodologies. SETTING: Certification examinations of MBPS. POPULATION: The 2013 and 2014 MBPS certification examinations, with 111 evidence items of the processes, followed for the assessment of 86 examinees. RESULTS: The checklist internal consistency was 0.89. Absolute interrater agreement was 0.34 for the 2013 and 0.66 for the 2014 editions of the examination. The 2013 examination complied with 55 (64%) of the checklist 86 items, in 2014 with 72 (84%). CONCLUSION: In 2014, the certifying system reached a quality of 84%. For optimal fulfillment of its social responsibility, the MBPS is required to maintain its level of quality and attempt to improve its performance. PMID- 26143520 TI - Student Views on the Use of 2 Styles of Video-Enhanced Feedback Compared to Standard Lecture Feedback During Clinical Skills Training. AB - BACKGROUND: Feedback plays an important role in the learning process. However, often this may be delivered in an unstructured fashion that can detract from its potential benefit. Further, students may have different preferences in how feedback should be delivered, which may be influenced by which method they feel will lead to the most effective learning. The aim of this study was to evaluate student views on 3 different modes of feedback particularly in relation to the benefit each conferred. METHODS: Undergraduate medical students participating in a surgical suturing study were asked to give feedback using a semi-structured questionnaire. Discrete questions using a Likert scale and open responses were solicited. Students received either standard lecture feedback (SLF), individualized video feedback (IVF), or enhanced unsupervised video feedback (UVF). RESULTS: Students had a strong preference for IVF over UVF or SLF. These responses correlated with their perception of how much each type of feedback improved their performance. However, there was no statistical difference in suturing skill improvement between IVF and UVF, which were both significantly better than SLF. CONCLUSION: Students have a strong preference for IVF. This relates to a perception that this will lead to the greatest level of skill improvement. However, an equal effect in improvement can be achieved by using less resource-demanding UVF. PMID- 26143521 TI - What Shape is Your Resident in? Using a Radar Plot to Guide a Milestone Clinical Competency Discussion. AB - OBJECTIVE: One of the challenges for program directors (PDs) is to sort and weight the tidal wave of assessments that training programs create in the modern Milestone era. We evaluated whether the use of a radar plot (RP) would be helpful in sorting data and providing a graphic representation of each resident's progress. DESIGN: Using at least 2 different types of assessments for each of the 16 surgical Milestones, the data were ranked and weighted by a predetermined method embedded in a computerized workbook (Excel). This process created a unique 16-spoked RP for each resident (Fig. below). The RP allowed the faculty to see areas of weakness (shown by concavity) and allowed an overall grade calculated as a ratio of the area of the smooth outer circle (faculty expectations, triangles) and the resident's unique radar shape (resident performance, squares). To help us validate our new tool, we looked at whether residents with recent remedial issues "looked" different from residents without remedial issues. RESULTS: Of our 30 categorical residents, 8 had significant areas of concavities, suggesting possible areas of improvement. Of these 8 residents, 4 had been on a remediation program in the last 18 months. The average ratio of performance/expectations was 0.709. The 4 residents on recent remediation had a ratio of 0.616 when compared with 0.723 for the residents without remedial issues (p < 0.009). CONCLUSIONS: Many exciting challenges await PDs, as we evolve to a competency-based evaluation system. The use of an evaluation summary tool using RPs may aid PDs in leading clinical competency discussions and in monitoring a resident's progress over time. PMID- 26143523 TI - Comparison of the effect of different sampling modes on computer analysis of cardiotocograms. AB - BACKGROUND: Cardiotocographic (CTG) monitors may provide fetal heart rate (FHR) signals as beat-to-beat (BTB) or alternatively at a fixed sampling rate. The aim of this study was to assess the effect of different sampling modes on the evaluation provided by a commercially available system for computer analysis of CTGs. METHODS: Internal FHR signals were acquired during the last hour of labor in 27 singleton term cephalic pregnancies, using the STAN S31((r)) fetal monitor (Neoventa, Gothemburg, Sweden). BTB and 4 Hz sampling outputs of the monitor were compared using the Omniview-SisPorto((r)) system for computer analysis of CTGs (Speculum, Lisbon, Portugal). The following parameters were analyzed: signal loss, signal quality, baseline, accelerations, decelerations, percentage of abnormal short-term variability (%aSTV), abnormal long-term variability (%aLTV), average short-term variability (avSTV) and the system's clinical alerts. Statistical inference was performed using the Spearman correlation coefficient, 95% nonparametric confidence intervals, Wilcoxon and McNemar statistical tests, setting significance at 0.05, and a non-parametric measure of disagreement (valued 0-1 from lowest to highest disagreement). RESULTS: Comparing BTB with 4 Hz sampling, the median values for signal quality (95% versus 96%), number of accelerations (5 versus 7) and %aSTV (31 versus 39) were significantly lower in the former. On the other hand, with BTB signals the median value of avSTV was significantly higher (3.1 versus 2.3). Nevertheless, BTB and 4 Hz parameters were highly correlated (r=0.89-0.97), and there were no significant differences in the quantification of the number of decelerations or in the clinical alerts elicited by the system. CONCLUSIONS: In conclusion, different sampling modes have a significant effect on the parameters provided by computer analysis of CTGs that are related with the quantification of STV, with a small impact on baseline estimation and on the subsequent quantification of accelerations. However, there does not seem to be significant impact on the quantification of decelerations or on the alerts provided by the system. PMID- 26143522 TI - Pheromone processing in Drosophila. AB - Understanding how sensory stimuli are processed in the brain to instruct appropriate behavior is a fundamental question in neuroscience. Drosophila has become a powerful model system to address this problem. Recent advances in characterizing the circuits underlying pheromone processing have put the field in a position to follow the transformation of these chemical signals all the way from the sensory periphery to decision making and motor output. Here we describe the latest advances, outline emerging principles of pheromone processing and discuss future questions. PMID- 26143524 TI - Evolutionary morphology of the hemolymph vascular system of basal araneomorph spiders (Araneae: Araneomorphae). AB - The superfamily Austrochiloidea (Austrochilidae and Gradungulidae) take a pivotal position in araneomorph spider phylogeny. In this discussion crevice weaver spiders (Filistatidae) are of equal interest. Especially data from these phylogenetically uncertain yet basal off branching groups can enlighten our understanding on the evolution of organ systems. In the course of a survey on the evolutionary morphology of the circulatory system in spiders we therefore investigated the hemolymph vascular system in two austrochiloid and one filistatid species. Additionally some data on a hypochilid and a gradungulid species are included. Using up-to-date morphological methods, the vascular systems in these spiders are visualized three dimensionally. Ground pattern features of the circulatory systems in austrochiloid spiders are presented and the data discussed along recent lines of phylogenetic hypotheses. Special topics highlighted are the intraspecific variability of the origins of some prosomal arteries and the evolutionary correlation of respiratory and circulatory systems in spiders. PMID- 26143525 TI - Protracted late infantile ceroid lipofuscinosis due to TPP1 mutations: Clinical, molecular and biochemical characterization in three sibs. AB - OBJECTIVE: This work investigated the molecular cause responsible for a late onset parkinsonism-dystonia phenotype in three Italian siblings, and clinically characterize this condition. METHODS: Extensive neurophysiological and neuroradiological exams were performed on the three sibs. Most frequent late onset metabolic diseases were ruled out through laboratory and biochemical analyses. A whole exome sequencing (WES) approach was used to identify the molecular cause underlying this condition. RESULTS AND CONCLUSIONS: Peculiar neurologic phenotype was characterized by dystonia-parkinsonism, cognitive impairment, gait ataxia and apraxia, pyramidal signs. WES analysis allowed the identification of a compound heterozygosity for two nucleotide substitutions (c.1340G>A, p.R447H; c.790C>T, p.Q264X) affecting the TPP1 gene in the three affected siblings. Biochemical analyses demonstrated abrogated TPP1 catalytic activity in primary skin fibroblasts, but revealed residual activity in leukocytes. Our findings document that late infantile neuronal ceroid lipofuscinosis (CLN2), which is caused by TPP1 gene mutations, should be considered in the differential diagnosis of autosomal recessive dystonia parkinsonism syndromes. The availability of enzyme replacement therapy and other therapeutic approaches for ceroid lipofuscinoses emphasizes the value of reaching an early diagnosis in patients with atypical and milder presentation of these disorders. PMID- 26143526 TI - MFN2-related neuropathies: Clinical features, molecular pathogenesis and therapeutic perspectives. AB - Mitofusin 2 (MFN2) is a GTPase dynamin-like protein of the outer mitochondrial membrane, encoded in the nuclear genome by the MFN2 gene located on the short (p) arm of chromosome 1. MFN2 protein is involved in several intracellular pathways, but is mainly involved in a network that has an essential role in several mitochondrial functions, including fusion, axonal transport, interorganellar communication and mitophagy. Mutations in the gene encoding MFN2 are associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a neurological disorder characterized by a wide clinical phenotype that involves the central and peripheral nervous system. Here, we present the clinical, genetic and neuropathological features of human diseases associated with MFN2 mutations. We also report proposed pathogenic mechanisms through which MFN2 mutations likely contribute to the development of neurodegeneration. MFN2-related disorders may occur more frequently than previously considered, and they may represent a paradigm for the study of the defective mitochondrial dynamics that seem to play a significant role in the molecular and cellular pathogenesis of common neurodegenerative diseases; thus they may also lead to the identification of related therapeutic targets. PMID- 26143527 TI - Factors influencing the survival period in Japanese patients with sporadic Creutzfeldt-Jakob disease. AB - Although Japanese cases of sporadic Creutzfeldt-Jakob disease (sCJD) generally involve longer survival periods compared to those from other countries, details regarding the factors influencing survival are unclear. To determine the influence of certain factors on survival, we retrospectively assessed 51 Japanese MM1-type sCJD patients with respect to background, clinical course, and disease management. No significant differences were found between men and women, tracheotomy and nontracheotomy patients, or patients treated in public and other types of hospitals. Although the survival period of tube-fed patients was significantly longer than that of patients who were not tube fed, survival of patients fed via a nasal tube did not differ significantly from that of gastrostomy-fed patients. The proportion of tube-fed patients was 68.6% (35/51). Disease duration was not significantly associated with age or year of onset. However, it was associated with time from onset to first recognition of myoclonus, first recognition of periodic sharp-wave complexes on electroencephalogram, and progression to the akinetic mutism state. Mechanical ventilation was not performed for any patient. Because the total disease duration increased in cases with a slowly progressive clinical course as a natural outcome, we concluded that the most crucial factor contributing to the prolonged survival of Japanese sCJD patients was tube feeding once the akinetic mutism state had been reached. PMID- 26143529 TI - The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients. AB - Although age is thought to correlate with the prognosis of glioma patients, the most appropriate age-group classification standard to evaluate prognosis had not been fully studied. This study aimed to investigate the influence of age-group classification standards on the prognosis of patients with high-grade hemispheric glioma (HGG). This retrospective study of 125 HGG patients used three different classification standards of age-groups (<= 50 and >50 years old, <= 60 and >60 years old, <= 45 and 45-65 and >= 65 years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan-Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups <= 50 and > 50 years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was <= 50 and > 50 years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients. PMID- 26143528 TI - Association of the Charcot-Marie-Tooth disease gene ARHGEF10 with paclitaxel induced peripheral neuropathy in NCCTG N08CA (Alliance). AB - The predisposition of patients to develop polyneuropathy in response to toxic exposure may have a genetic basis. The previous study Alliance N08C1 found an association of the Charcot-Marie-Tooth disease (CMT) gene ARHGEF10 with paclitaxel chemotherapy induced peripheral neuropathy (CIPN) related to the three non-synonymous, recurrent single nucleotide variants (SNV), whereby rs9657362 had the strongest effect, and rs2294039 and rs17683288 contributed only weakly. In the present report, Alliance N08CA was chosen to attempt to replicate the above finding. N08CA was chosen because it is the methodologically most similar study (to N08C1) performed in the CIPN field to date. N08CA enrolled patients receiving the neurotoxic chemotherapy agent paclitaxel. Polyneuropathy was assessed by serial repeat administration of the previously validated patient reported outcome instrument CIPN20. A study-wide, Rasch type model was used to perform extreme phenotyping in n=138 eligible patients from which "cases" and "controls" were selected for genetic analysis of SNV performed by TaqMan PCR. A significant association of ARHGEF10 with CIPN was found under the pre-specified primary endpoint, with a significance level of p=0.024. As in the original study, the strongest association of a single SNV was seen for rs9657362 (odds ratio=3.56, p=0.018). To further compare results across the new and the previous study, a statistical "classifier" was tested, which achieved a ROC area under the curve of 0.60 for N08CA and 0.66 for N08C1, demonstrating good agreement. Retesting of the primary endpoint of N08C1 in the replication study N08CA validated the association of ARHGEF10 with CIPN. PMID- 26143530 TI - Integrin LFA-1 regulates cell adhesion via transient clutch formation. AB - Integrin LFA-1 regulates immune cell adhesion and trafficking by binding to ICAM 1 upon chemokine stimulation. Integrin-mediated clutch formation between extracellular ICAM-1 and the intracellular actin cytoskeleton is important for cell adhesion. We applied single-molecule tracking analysis to LFA-1 and ICAM-1 in living cells to examine the ligand-binding kinetics and mobility of the molecular clutch under chemokine-induced physiological adhesion and Mn(2+) induced tight adhesion. Our results show a transient LFA-1-mediated clutch formation that lasts a few seconds and leads to a transient lower-mobility is sufficient to promote cell adhesion. Stable clutch formation was observed for Mn(2+)-induced high affinity LFA-1, but was not required for physiological adhesion. We propose that fast cycling of the clutch formation by intermediate affinity integrin enables dynamic cell adhesion and migration. PMID- 26143531 TI - Antioxidative effects of magnetized extender containing bovine serum albumin on sperm oxidative stress during long-term liquid preservation of boar semen. AB - Magnetized water is defined as water that has passed through a magnet and shows increased permeability into cells and electron-donating characteristics. These attributes can protect against membrane damage and remove reactive oxygen species (ROS) in mammalian cells. We explored the effects of improved magnetized semen extenders containing bovine serum albumin (BSA) as antioxidants on apoptosis in boar sperm. Ejaculated semen was diluted in magnetized extender (0G and 6000G) with or without BSA (0G + BSA and 6000G + BSA), and sperm were analyzed based on viability, acrosome reaction, and H2O2 level of live sperm using flow cytometry. Sperm were then preserved for 11 days at 18 degrees C. We found that viability was significantly higher in 6000G + BSA than under the other treatments (P < 0.05). The acrosome reaction was significantly lower in the 6000G + BSA group compared with the other treatments (P < 0.05). Live sperm with high intracellular H2O2 level were significantly lower in the 6000G + BSA group than under other treatments (P < 0.05). Based on our results, magnetized extenders have antioxidative effects on the liquid preservation of boar sperm. PMID- 26143534 TI - Characterization and mechanical separation of metals from computer Printed Circuit Boards (PCBs) based on mineral processing methods. AB - In this paper, a novel mechanical process is proposed for enriching metal content of computer Printed Circuit Boards (PCBs). The PCBs are crushed and divided into three different size fractions namely: -0.59, +0.59 to 1.68 and +1.68 mm. Wet jigging and froth flotation methods are selected for metal enrichment. The coarse size fraction (+1.68 mm) is processed by jigging. The plastic free product is grinded and screened. The oversized product is separated as the first concentrate. It was rich of metal because the grinding process was selective. The undersized product is processed by froth flotation. Based on the obtained results, the middle size fraction (+0.59 to 1.68 mm) and the small size fraction (-0.59 mm) are processed by wet jigging and froth flotation respectively. The wet jigging process is optimized by investigating the effect of pulsation frequency and water flow rate. The results of examining the effect of particle size, solid to liquid ratio, conditioning time and using apolar collector showed that collectorless flotation is a promising method for separating nonmetals of PCBs. 95.6%, 97.5% and 85% of metal content of coarse size, middle size and small size fraction are recovered. The grades of obtained concentrates were 63.3%, 92.5% and 75% respectively. The total recovery is calculated as 95.64% and the grade of the final concentrate was 71.26%. Determining the grade of copper and gold in the final product reveals that 4.95% of copper and 24.46% of gold are lost during the concentration. The major part of the lost gold is accumulated in froth flotation tail. PMID- 26143532 TI - Transcriptome and ultrastructural changes in dystrophic Epidermolysis bullosa resemble skin aging. AB - The aging process of skin has been investigated recently with respect to mitochondrial function and oxidative stress. We have here observed striking phenotypic and clinical similarity between skin aging and recessive dystrophic Epidermolysis bullosa (RDEB), which is caused by recessive mutations in the gene coding for collagen VII,COL7A1. Ultrastructural changes, defects in wound healing, and inflammation markers are in part shared with aged skin. We have here compared the skin transcriptomes of young adults suffering from RDEB with that of sex- and age-matched healthy probands. In parallel we have compared the skin transcriptome of healthy young adults with that of elderly healthy donors. Quite surprisingly, there was a large overlap of the two gene lists that concerned a limited number of functional protein families. Most prominent among the proteins found are a number of proteins of the cornified envelope or proteins mechanistically involved in cornification and other skin proteins. Further, the overlap list contains a large number of genes with a known role in inflammation. We are documenting some of the most prominent ultrastructural and protein changes by immunofluorescence analysis of skin sections from patients, old individuals, and healthy controls. PMID- 26143533 TI - Diabetes among refugee populations: what newly arriving refugees can learn from resettled Cambodians. AB - A growing body of literature suggests that cardiometabolic disease generally and type 2 diabetes specifically are problems among refugee groups. This paper reviews rates of cardiometabolic disease and type 2 diabetes among refugees and highlights their unique risk factors including history of malnutrition, psychiatric disorders, psychiatric medications, lifestyle changes toward urbanization and industrialization, social isolation, and a poor profile on the social determinants of health. Promising interventions are presented for preventing and treating diabetes in these groups. Such interventions emphasize well-coordinated medical and mental health care delivered by cross-cultural and multidisciplinary teams including community health workers that are well integrated into the community. Finally, recommendations for service, policy, and research are made. The authors draw on local data and clinical experience of our collective work with Cambodian American refugees whose 30-year trajectory illustrates the consequences of ignoring diabetes and its risk factors in more recent, and soon to be arriving, refugee cohorts. PMID- 26143535 TI - Environmental evaluation of green concretes versus conventional concrete by means of LCA. AB - A number of green concrete mixes having similar basic properties were evaluated from the environmental point of view by means of the Life Cycle Assessment method, and compared with a corresponding conventional concrete mix. The investigated green concrete mixes were prepared from three different types of industrial by-products, i.e. (1) foundry sand, and (2) steel slag, both of which were used as manufactured aggregates, and (3) fly ash, which was used as a mineral admixture. Some green concrete mixes were also prepared from a recycled aggregate, which was obtained from reinforced concrete waste. In some of the green concrete mixes the recycled aggregate was used in combination with the above-mentioned types of manufactured aggregate and fly ash. All of these materials are able, to some extent, to replace natural aggregate or Portland cement in concrete mixes, thus providing an environmental benefit from the point of view of the saving of natural resources. Taking into account consequential modelling, the credit related to the avoidance of the need to dispose of the waste materials is considered as a benefit. In case of the recycling of waste concrete into aggregate, credit is attributed to the recovery of scrap iron from the steel reinforcement. In the case of the use of steel slag, credit is attributed to the recovery of metals, which are extracted from the slag before being used as an alternative material. The disadvantage of using alternative materials and recycled aggregates can sometimes be their relatively long delivery distance. For this reason, a transport sensitivity analysis was carried out. The results indicate that the use of the discussed alternative and recycled materials is beneficial in the concrete production industry. Preference is given to the fly ash and foundry sand scenarios, and especially to those scenarios which are based on the combined use of recycled aggregate with these two alternative materials. It was found that longer delivery distances of the alternative materials do not necessarily affect the results significantly. However, variable delivery distances may have a greater effect when choosing between different alternative scenarios. PMID- 26143536 TI - Oxytocin enhances implicit social conformity to both in-group and out-group opinions. AB - People often alter their own preferences when facing conflicting opinions expressed by others. This is known as the social conformity effect and tends to be stronger in response to opinions expressed by in-group relative to out-group members. The hypothalamic neuropeptide oxytocin promotes in-group favoritism, elicits parochial altruism, and stimulates in-group conformity under explicit social pressure. In a double-blind, placebo-controlled design experiment using a facial attractiveness judgment task, we therefore investigated whether social conformity to either in-group or out-group opinions is influenced by intranasal oxytocin treatment when social pressure is implicit. After oxytocin or placebo treatment, male participants were asked to rate the attractiveness of unfamiliar Chinese female faces, and then they were informed of ratings given by peers from an in-group (Chinese) and out-group (Japanese) simultaneously. They were subsequently asked unexpectedly to re-rate the same faces. Results showed that oxytocin increased conformity to both in- and out-group opinions. Thus oxytocin promotes conformity to opinions of both in- and out-group members when social pressure is implicit, suggesting that it facilitates 'tend and befriend' behaviors by increasing the general level of social conformity. PMID- 26143537 TI - Sex-specific regulation of NUCB2/nesfatin-1: Differential implication in anxiety in obese men and women. AB - Nesfatin-1 is cleaved from nucleobindin2 (NUCB2) and implicated in the regulation of hunger and satiety as anorexigenic peptide hormone. Circulating NUCB2/nesfatin 1 is elevated in obesity and decreased in anorexia nervosa. In addition, a role in the regulation of stress, anxiety and depression has been demonstrated. First evidence suggested that NUCB2/nesfatin-1 might be regulated in a sex-specific manner. Thus, we investigated NUCB2/nesfatin-1 plasma levels in association with perceived stress, anxiety and depressiveness in obese men and women. We enrolled 140 inpatients (87 female, 53 male; body mass index, BMI, 30.3-81.7 kg/m(2)) hospitalized due to obesity with mental and somatic comorbidities. Perceived stress (PSQ-20), anxiety (GAD-7), and depressiveness (PHQ-9) were measured psychometrically, and at the same time NUCB2/nesfatin-1 plasma levels by ELISA. Males and females did not differ in terms of age and BMI. NUCB2/nesfatin-1 did not show a correlation with age or BMI. Mean NUCB2/nesfatin-1 levels (+25%, p<0.001) as well as mean scores for perceived stress (+26%, p < 0.01), anxiety (+54%, p < 0.001) and depressiveness (+32%, p = 0.02) were higher in females compared to males. Scores for perceived stress (r = 0.39; p < 0.001) and depressiveness (r = 0.35; p < 0.01) showed a positive correlation with NUCB2/nesfatin-1 in women, while in men no correlation was observed (p>0.19). The strongest association was observed between NUCB2/nesfatin-1 and anxiety with a positive correlation in women (r = 0.54; p < 0.001), while in men even an inverse correlation was found (r = -0.32; p = 0.03). This result was reflected in higher NUCB2/nesfatin-1 levels in women with high versus low anxiety (+51%, p<0.001) and an opposite alteration in men (-17%, p = 0.04) after a median split into two groups with high and low anxiety. In conclusion, circulating NUCB2/nesfatin-1 showed a positive correlation with anxiety, perceived stress, and depressiveness in obese women. In men, no correlation with perceived stress and depressiveness was observed, whereas the association with anxiety was inverse, pointing towards a sex-specific regulation. These results corroborate the suggestion of NUCB2/nesfatin-1 being relevantly involved in the regulation of mood and stress in a sex-specific way. PMID- 26143538 TI - Maternal high-fat diet acts as a stressor increasing maternal glucocorticoids' signaling to the fetus and disrupting maternal behavior and brain activation in C57BL/6J mice. AB - Maternal diet during pregnancy can impact maternal behavior as well as the intrauterine environment, playing a critical role in programming offspring's physiology. In a preliminary study, we found a strong association between high fat diet (HFD) during pregnancy and increased cannibalistic episodes and dams' mortality during late pregnancy and parturition. Based upon these data, we hypothesized that HFD during pregnancy could negatively affect neuroendocrine and metabolic regulations occurring during the final stages of pregnancy, thereby disrupting maternal behavior. To test this hypothesis, female C57BL/6J mice were fed HFD or control diet for 11 weeks until three days before the expected delivery date. Basal corticosterone plasma levels and brain levels of c-Fos were measured both before and after delivery, in addition to leptin levels in the adipose tissue. Dam's emotional behavior and social anxiety, in addition to locomotor activity were assessed before parturition. Data show that HFD led to aberrant maternal behavior, dams being characterized by behaviors related to aggression toward an unfamiliar social stimulus in the social avoidance test, in addition to decreased locomotor activity. Neural activity in HFD dams was reduced in the olfactory bulbs, a crucial brain region for social and olfactory recognition hence essential for maternal behavior. Furthermore, HFD feeding resulted in increased circulating levels of maternal corticosterone and decreased levels of leptin. In addition, the activity of the protective 11beta dehydrogenase-2 (11beta-HSD-2) barrier in the placenta was decreased together with 11beta-dehydrogenase-1 (11beta-HSD-1) gene expression. Overall, these data suggest that HFD acts as a stressful challenge during pregnancy, impairing the neuroendocrine system and the neural activity of brain regions involved in the processing of relevant olfactory stimuli, with negative consequences on maternal physiology and behavior. PMID- 26143539 TI - Maternal stress predicts altered biogenesis and the profile of mitochondrial proteins in the frontal cortex and hippocampus of adult offspring rats. AB - Currently, much attention is focused on the influence of mitochondrial disturbances at the onset of depression. The goal of this study was to investigate the impact of prenatal stress (an animal model of depression) on the mitochondrial biogenesis proteins and mitoproteome profile in the frontal cortex and hippocampus of adult 3-month-old male rats following a prenatal stress procedure. Our results show that rats that were exposed to prenatal stress stimuli displayed depression-like behaviors based on the sucrose preference and elevated plus maze tests. It has been found that the level of the PGC-1alpha protein was reduced in the frontal cortex and hippocampus of the adult offspring after the prenatal stress procedure. Moreover, in the frontal cortex, the level of the pro-apoptotic protein Bax was up-regulated. Two-dimensional electrophoresis coupled with mass spectrometry showed the statistically significant down-regulation of the mitochondrial ribosomal protein L12 (Mrpl12) and mitochondrial NADH dehydrogenase [ubiquinone] flavoprotein 2 (NDUFV2) as well as the up-regulation of the Tubulin Polymerization Promoting Proteins (Tppp/p25) in the frontal cortex. In contrast, in the hippocampus, the mitochondrial pyruvate dehydrogenase E1 component subunit beta, the voltage-dependent anion selective channel protein 2 (VDAC2), and the GTP-binding nuclear protein RAN (RAN) were down-regulated and the expression of phosphatidylethanolamine-binding protein 1 (PEBP-1) was enhanced. These findings provide new evidence that stress during pregnancy may lead not only to behavioral deficits, but also to disturbances in the brain mitoproteome profile in adult rat offspring. PMID- 26143540 TI - Support Experienced by Patients Living with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension. AB - BACKGROUND: As pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating and fatal diseases it is essential to increase the understanding of patients' experience of support. The aim was to describe patients' experiences of support while living with PAH or CTEPH. METHODS: Seventeen patients (13 women and four men) aged 28-73 years were strategically selected from a regional PAH centre and individually interviewed. The answers were analysed using qualitative content analysis. RESULTS: Three categories that describe patients' experiences of support emerged: Support linked to the healthcare; support linked to the private sphere; and support linked to persons outside the private sphere. CONCLUSION: Healthcare practitioners must work more in collaboration to detect patients' need for support and to develop the patient's own skills to manage daily life. The PAH teams should tailor interventions to provide emotional, informational and instrumental support and guidance to patients and their families. PMID- 26143541 TI - Vitrectomy with Internal Limiting Membrane Repositioning and Autologous Blood for Macular Hole Retinal Detachment in Highly Myopic Eyes. AB - PURPOSE: To investigate the surgical results of macular hole retinal detachment (MHRD) repaired using vitrectomy combined with inverted internal limiting membrane repositioning (ILMR) and autologous blood clot (ABC) in highly myopic eyes. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Twenty seven cases of MHRD. METHODS: Twenty-seven cases of highly myopic eyes with MHRD in 27 patients who underwent a vitrectomy combined with ILMR and ABC and were followed up over 6 months were reviewed. The anatomic outcomes of MHRD were evaluated by fundus examinations and optical coherence tomography. The preoperative and postoperative best-corrected visual acuities (BCVAs) were compared as the functional outcome. MAIN OUTCOME MEASURES: Retinal reattachment, macular hole (MH) closure, and BCVA before and after surgery. RESULTS: In total, women accounted for 85% (23/27) of the MHRD patients. The mean age was 59.1+/ 10.6 years. The mean axial length was 29.37+/-1.92 mm. Type 1 MHRD was present in 9 eyes, and type 2 MHRD was present in 18 eyes. After a single surgery, the retina was attached and the hole was closed in 26 eyes (96%), and 100% retinal attachment was achieved by another vitrectomy for rhegmatogenous retinal detachment that occurred 3 months after the initial surgery. A parafoveal unclosed hole was found in 1 eye (4%) during the follow-up period, and the patient did not undergo further treatment. Three eyes with a closed hole showed persistent subretinal fluid (SRF) after gas absorption. In 2 of these cases, the fluid absorbed completely during the follow-up period, but 1 eye exhibited persistent SRF, which was resolved progressively during the 12 months of follow up. The surgery significantly improved the BCVAs {from 1.8+/-0.7 logarithm of the minimum angle of resolution units to 1.3+/-0.7 logarithm of the minimum angle of resolution units (P = 0.001)} at 3 and 6 months and at the last visit after surgery. Seven patients underwent cataract surgery during the follow-up period. CONCLUSIONS: A vitrectomy combined with ILMR and ABC is effective for closing MHs and reattaching the retina and significantly improves the postoperative BCVA in MHRD patients. PMID- 26143543 TI - Chromium (VI) potentiates the DNA adducts (O(6)-methylguanine) formation of N nitrosodimethylamine in rat: implication on carcinogenic risk. AB - Chromium (VI) [Cr(VI)] and nitrosamines such as N-nitrosodimethylamine (NDMA) exist commonly in the environment. To evaluate the potential influence of Cr(VI) co-exposure on the carcinogenic risk of NDMA, Female Wistar rats were treated with various concentrations of Cr(VI) and/or NDMA via drinking water for 15days and the DNA adducts (O(6)-methylguanine, O(6)-MeG) of NDMA in liver tissue was used as a bioindicator. The results showed that Cr(VI) synergistically enhanced the O(6)-MeG formation, which could lead to an increase in DNA damage and carcinogenic potential. Although Cr(VI) did not alter the CYP 2E1 enzyme activity, it decreased GSH content, which would be an potential mechanism for the potentiated O(6)-MeG formation by Cr(VI) co-exposure. These results would contribute to the development of quantitative risk assessment of NDMA or even for a group of nitrosamines under environmental mixture exposure. PMID- 26143542 TI - Visual Function in Carriers of X-Linked Retinitis Pigmentosa. AB - PURPOSE: To determine the frequency and severity of visual function loss in female carriers of X-linked retinitis pigmentosa (XLRP). DESIGN: Case series. PARTICIPANTS: Two hundred seventy-six XLRP carriers with cross-sectional data (n = 242) and longitudinal data (n = 34; median follow-up, 16 years; follow-up range, 3-37 years). Half of the carriers were from RPGR- or RP2-genotyped families. METHODS: Retrospective medical records review. MAIN OUTCOME MEASURES: Visual acuities, visual field areas, final dark adaptation thresholds, and full field electroretinography (ERG) responses to 0.5-Hz and 30-Hz flashes. RESULTS: In genotyped families, 40% of carriers showed a baseline abnormality on at least 1 of 3 psychophysical tests. There was a wide range of function among carriers. For example, 3 of 121 (2%) genotyped carriers were legally blind because of poor visual acuity, some as young as 35 years. Visual fields were less affected than visual acuity. In all carriers, the average ERG amplitude to 30-Hz flashes was approximately 50% of normal, and the average exponential rate of amplitude loss over time was half that of XLRP males (3.7%/year vs. 7.4%/year, respectively). Among obligate carriers with affected fathers, sons, or both, 53 of 55 (96%) had abnormal baseline ERG results. Some carriers who initially had completely normal fundi in both eyes went on to experience moderately decreased vision, although not legal blindness. Among carriers with RPGR mutations, those with mutations in ORF15, compared with those in exons 1-14, had worse final dark adaptation thresholds and lower 0.5-Hz and 30-Hz ERG amplitudes. CONCLUSIONS: Most carriers of XLRP had mildly or moderately reduced visual function but rarely became legally blind. In most cases, obligate carriers could be identified by ERG testing. Carriers of RPGR ORF15 mutations tended to have worse visual function than carriers of RPGR exon 1 through 14 mutations. Because XLRP carrier ERG amplitudes and decay rates over time were on average half of those of affected men, these observations were consistent with the Lyon hypothesis of random X inactivation. PMID- 26143544 TI - New risk indicator approach for Operators, Workers, Bystanders and Residents for a sustainable use of plant protection products. AB - In 2009, the European Union adopted the Directive on Sustainable Use of pesticides (SUD, Directive 2009/128/EC) establishing a framework for achieving a sustainable use of Plant Protection Products (PPPs) through reducing the risks and impacts of PPP use on human health and the environment, promoting integrated pest management and stimulating effective non-chemical alternatives. The core idea of the SUD is that it is necessary to monitor the use of PPPs through the implementation of an appropriate set of risk indicators to monitor progress and trends in risk reduction within the Member States. To contribute to this direction, following a comprehensive analysis of the risk (including procedures of risk assessment and risk management) and involving stakeholders in the decision process, specific toolboxes of practical indirect risk indicators of exposure of Operators, Workers, Bystanders and Residents were developed and are now available to be used by Member States (MSs) based on their specific context. PMID- 26143545 TI - Detection of antibiotic resistance, virulence gene determinants and biofilm formation in Aeromonas species isolated from cattle. AB - This study aimed to assess the antibiogram of Aeromonas strains recovered from cattle faeces and the potential pathogenic status of the isolates. The antibiogram of the Aeromonas isolates demonstrated total resistance to clindamycin oxacillin, trimethoprim, novobiocin and ticarcillin. However, Aeromonas strains were sensitive to cefotaxime, oxytetracycline and tobramycin. The Aeromonas strains from Lovedale and Fort Cox farms were found to possess some virulence genes. The percentage distribution was aer 71.4%, ast 35.7%, fla 60.7%, lip 35.7% and hlyA 25% for Lovedale farm and aer 63.1%, alt 10.5%, ast 55.2%, fla 78.9%, lip 21% and hlyA 35.9% for Fort Cox farm. Class 1 integron was present in 27% of Aeromonas isolates; the bla TEM gene was present in 34.8%, while the blaP1 class A beta-lactamase gene was detected in 12.1% of the isolates. Approximately 86% of the isolates formed a biofilm on microtitre plates. The presence of multiple antibiotic resistance and virulence genes in Aeromonas isolates from cattle faeces reveals the pathogenic and infectious importance of these isolates and is of great significance to public health. The possession of a biofilm forming capability by such isolates may lead to difficulty during the management of infection related to Aeromonas species. PMID- 26143546 TI - Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling. AB - The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1-7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-beta1. Additionally, ACE2 overexpression also modulated the tachypacing induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin-angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF. PMID- 26143548 TI - Our Journals Arthroscopy and Arthroscopy Techniques Are Complementary. AB - Your Editors are devoted to both of our journals, Arthroscopy and Arthroscopy Techniques. This month's content includes clinically relevant hip, knee, and shoulder research, and surgical techniques. PMID- 26143547 TI - Enhanced precision of ankle torque measure with an open-unit dynamometer mounted with a 3D force-torque sensor. AB - PURPOSE: Many studies have focused on maximum torque exerted by ankle joint muscles during plantar flexion. While strength parameters are typically measured with isokinetic or isolated ankle dynamometers, these devices often present substantial limitations for the measurement of torque because they account for force in only 1 dimension (1D), and the device often constrains the body in a position that augments torque through counter movements. The purposes of this study were to determine the contribution of body position to ankle plantar flexion torque and to assess the use of 1D and 3D torque sensors. METHODS: A custom designed 'Booted, Open-Unit, Three dimension, Transportable, Ergometer' (B.O.T.T.E.) was used to quantify plantar flexion in two conditions: (1) when the participant was restrained within the unit (locked-unit) and (2) when the participant's position was independent of the ankle dynamometer (open-unit). Ten young males performed maximal voluntary isometric plantar-flexion contractions using the B.O.T.T.E. in open and locked-unit mechanical configurations. RESULTS: The B.O.T.T.E. was reliable with ICC higher than 0.90, and CV lower than 7 %. The plantar-flexion maximal resultant torque was significantly higher in the locked unit compared with open-unit configuration (P < 0.001; +61 to +157 %) due to the addition of forces from the body being constrained within the testing device. A 1D compared with 3D torque sensor significantly underestimated the proper capacity of plantar-flexion torque production (P < 0.001; -37 to -60 %). CONCLUSIONS: Assessment of plantar-flexion torque should be performed with an open-unit dynamometer mounted with a 3D sensor that is exclusive of accessory muscles but inclusive of all ankle joint movements. PMID- 26143549 TI - Surgical and Histologic Confirmation of Psoas Regeneration After Arthroscopic Tenotomy. PMID- 26143550 TI - Editorial Commentary: Arthroscopy Is a Generally Effective Treatment for Septic Arthritis. AB - Hip bacterial septic arthritis is an indication for arthroscopy in combination with medical management. After arthroscopy, patients must be vigilantly observed; some patients require more than one irrigation and debridement. PMID- 26143551 TI - Editorial Commentary: Operative Treatment of Patellar Dislocation. AB - Modern medial patellofemoral ligament reconstruction results in improved outcomes for patients with patellar instability. PMID- 26143552 TI - Editorial Commentary: Hip Femoroacetabular Impingement Surgery Requires Improved Radiologic Research and Expert Understanding of Hip Clinical Examination. AB - Hip femoroacetabular impingement (FAI) is overwhelmingly the primary cause of revision surgery after hip arthroscopy. FAI imaging is confusing and requires additional research. Therefore, hip arthroscopic surgeons must become experts at clinical evaluation and examination. PMID- 26143553 TI - Editorial Commentary: Hamstring Autografts Are More Frequently Associated With ACL Infection. AB - Hamstring autograft is associated with higher rates of ACL infection than other grafts. Hamstring grafts presoaked with vancomycin are recommended. PMID- 26143554 TI - Editorial Commentary: Radiographic Inclusion and Exclusion Diagnostic Criteria for Femoroacetabular Impingement Require Confirmation. AB - Femoroacetabular impingement radiographic diagnosis is a hot topic because sensitivity and specificity, and intraobserver and interobserver observational consistency, require confirmation. As a result, hip arthroscopic surgeons must rely on expert clinical examination. PMID- 26143555 TI - Nausea and Vomiting in Early Pregnancy of Adolescents: Relationship with Depressive Symptoms. AB - STUDY OBJECTIVE: To determine the relationship between severity of nausea and vomiting during pregnancy (NVP) and depressive symptoms in pregnant adolescents. DESIGN: Prospective cross-sectional study. SETTING: A maternity research hospital outpatient clinic, Ankara, Turkey. PARTICIPANTS: A total of 200 pregnant adolescents. INTERVENTIONS AND MAIN OUTCOME MEASURES: Demographic features and obstetric histories of the participants were assessed. The Rhodes test was performed to determine nausea and vomiting severity in a face-to-face interview, and the self-reported Edinburgh Postnatal Depression Scale was administered with supervision. RESULTS: The Rhodes test results showed that 52/200 patients (26%) were classified with none, 83/200 patients (41.5%) with mild, 48/200 patients (24.0%) with moderate, and 17/200 patients (8.5%) with severe symptoms. The mean depression score in the severe vomiting group was significantly higher than that in the no NVP and mild NVP groups (P = .028 and .041, respectively). No differences were found between the other groups. CONCLUSION: Severe nausea and vomiting was associated with greater depressive symptom severity in pregnant adolescents. PMID- 26143556 TI - Racial and/or Ethnic Differences in Formal Sex Education and Sex Education by Parents among Young Women in the United States. AB - STUDY OBJECTIVE: We sought to investigate the associations between race and/or ethnicity and young women's formal sex education and sex education by parents. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of a nationally representative sample of 1768 women aged 15-24 years who participated in the 2011 2013 National Survey of Family Growth. INTERVENTIONS AND MAIN OUTCOME MEASURES: We assessed 6 main outcomes: participants' report of: (1) any formal sex education; (2) formal contraceptive education; (3) formal sexually transmitted infection (STI) education; (4) any sex education by parents; (5) contraceptive education by parents; and (6) STI education by parents. The primary independent variable was self-reported race and/or ethnicity. RESULTS: Nearly all of participants (95%) reported any formal sex education, 68% reported formal contraceptive education, and 92% reported formal STI education. Seventy-five percent of participants reported not having any sex education by parents and only 61% and 56% reported contraceptive and STI education by parents, respectively. US born Hispanic women were more likely than white women to report STI education by parents (adjusted odds ratio = 1.87; 95% confidence interval, 1.17-2.99). No other significant racial and/or ethnic differences in sex education were found. CONCLUSION: There are few racial and/or ethnic differences in formal sex education and sex education by parents among young women. PMID- 26143557 TI - Medial and lateral foot loading and its effect on knee joint loading. AB - BACKGROUND: The medial knee contact force may be lowered by modified foot loading to prevent the progression of unilateral gonarthrosis but the real effects of such gait modifications are unknown. This study investigates how walking with a more medial or lateral rollover of the foot influences the in vivo measured knee contact forces. METHODS: Five subjects with telemeterized knee implants walked on a treadmill with pronounced lateral or medial foot loading. Acoustic feedback of peak foot pressure was used to facilitate the weight bearing shift. The resultant contact force, Fres, the medial contact force, Fmed, and the force distribution Fmed/Fres across the tibial plateau were computed from the measured joint contact loads. FINDINGS: During lateral foot loading, the two maxima of Fres during the stance phase, Peak 1 and Peak 2, increased by an average of 20% and 12%, respectively. The force distribution was changed by only -3%/+2%. As a result, Fmed increased by +16%/+17%. Medial foot loading, on the other hand, changed Fres only slightly, but decreased the distribution by -18%/-11%. This led to average reductions of Fmed by -18%/-18%. The reductions were realized by kinematic adaptations, such as increases of ankle eversion, step width and foot progression angle. INTERPRETATION: Medial foot loading consistently reduced the medial knee compartment, and may be a helpful gait modification for patients with pronounced medial gonarthrosis. The increase of Fmed during lateral foot loading was most likely caused by muscular co-contractions. Long-term training may lead to more efficient gait and reduce co-contractions. PMID- 26143558 TI - Factor analysis of the Edinburgh Handedness Inventory: Inconsistent handedness yields a two-factor solution. AB - While neuropsychology has long focused on direction (left versus right) of handedness, a growing body of evidence indicates that degree (inconsistent versus consistent) of handedness is at least as important. A promising feature of this new emphasis on degree of handedness is its greater concordance with extant genetic models of handedness, which posit a continuum from inconsistent handedness to consistent right-handedness, not a continuum from left- to right handedness. Specifically, departures away from consistent-right-handedness are thought to reflect the action of a neutral genetic factor that leaves handedness up to random environmental influences. To test whether handedness in inconsistent handers reflects the presence of multiple factors (compared to the presence of a single factor only in consistent-right-handers), factor analyses of handedness inventory scores were conducted on data from 987 right-handers, divided into consistent- versus inconsistent-handers. Consistent with predictions, analyses of inconsistent- versus consistent-handers yielded two versus one factor solutions, respectively. Results are discussed in terms of their potential implications for genetic models of handedness and for researchers interested in consistency of handedness as a neuropsychological variable. PMID- 26143559 TI - Assessing program sustainability in an eating disorder prevention effectiveness trial delivered by college clinicians. AB - Sustainability of the Body Project, a dissonance-based selective eating disorder prevention program supported by efficacy and effectiveness trials, has not previously been examined. This mixed-methods study collected qualitative and quantitative data on training, supervision, and the intervention from 27 mental health clinicians from eight US universities who participated in an effectiveness trial and quantitative data on 2-year sustainability of program delivery. Clinicians, who were primarily masters-level mental health providers, had limited experience delivering manualized interventions. They rated the training and manual favorably, noting that they particularly liked the role-plays of session activities and intervention rationale, but requested more discussion of processes and group management issues. Clinicians were satisfied receiving emailed supervision based on videotape review. They reported enjoying delivering the Body Project but reported some challenges with the manualized format and time constraints. Most clinicians anticipated running more groups after the study ended but only four universities (50%) reported providing additional Body Project groups at the 1-year follow-up assessment and sustained delivery of the groups decreased substantially two years after study completion, with only one university (12%) continuing to deliver groups. The most commonly reported barriers for conducting additional groups were limited time and high staff turnover. PMID- 26143560 TI - Modes of transmission of Simian T-lymphotropic Virus Type 1 in semi-captive mandrills (Mandrillus sphinx). AB - Non-human primates (NHPs) often live in inaccessible areas, have cryptic behaviors, and are difficult to follow in the wild. Here, we present a study on the spread of the simian T-lymphotropic Virus Type 1 (STLV-1), the simian counterpart of the human T-lymphotropic virus type 1 (HTLV-1) in a semi-captive mandrill colony. This study combines 28 years of longitudinal monitoring, including behavioral data, with a dynamic mathematical model and Bayesian inference. Three transmission modes were suspected: aggressive, sexual and familial. Our results show that among males, STLV-1 transmission occurs preferentially via aggression. Because of their impressive aggressive behavior male mandrills can easily transmit the virus during fights. On the contrary, sexual activity seems to have little effect. Thus transmission appears to occur primarily via male-male and female-female contact. In addition, for young mandrills, familial transmission appears to play an important role in virus spread. PMID- 26143561 TI - Radiology's Issues Are Still Important in Congress. PMID- 26143562 TI - Surely, You Jest. PMID- 26143563 TI - Guidelines for Management of Thyroid Nodules. PMID- 26143564 TI - The DICOM Radiation Dose Structured Report: What It Is and What It Is Not. PMID- 26143565 TI - Cancer Imaging Training in the 21st Century: An Overview of Where We Are, and Where We Need To Be. AB - Advances in cancer care over the past decade have significantly changed treatment algorithms and life expectancies. Time from cancer diagnosis to death is rapidly increasing, as new, targeted therapies are developed, many prolonging life even in advanced disease. Tumors are now genotyped at diagnosis, allowing personalization of treatment. The FDA is continually approving new drugs that quickly become the standard of care for common tumors; the impact of these drugs and their side effects is monitored with imaging, and accurate interpretation of imaging studies has become essential as these patients live longer. Oncologists rely on radiologists to understand new patterns of treatment response and novel drug side effects that are associated with new drug classes, increasing the knowledge required for accurate image interpretation. These factors have led to the demand for dedicated cancer imaging training for radiologists, who can integrate findings throughout the body on various imaging modalities. In addition, we need to expand radiology's focus beyond diagnosis, staging, and restaging of tumors, and include education about the influence of genomics on tumor characterization and guidance for cancer care, the spectrum of treatment response, and the imaging characteristics of adverse events associated with various therapies. The time has come, therefore, to formally incorporate, as part of radiology residency, a distinct cancer imaging curriculum that is standardized, tested, and will allow the new generation of radiologists to effectively communicate with and assist their oncologic colleagues and optimally contribute to the care of patients with cancer. PMID- 26143566 TI - Patient-Centered Clinical Training in Radiology. PMID- 26143567 TI - Does Breast Imaging Experience During Residency Translate Into Improved Initial Performance in Digital Breast Tomosynthesis? AB - PURPOSE: To determine the initial digital breast tomosynthesis (DBT) performance of radiology trainees with varying degrees of breast imaging experience. METHODS: To test trainee performance with DBT, we performed a reader study, after obtaining IRB approval. Two medical students, 20 radiology residents, 4 nonbreast imaging fellows, 3 breast imaging fellows, and 3 fellowship-trained breast imagers reviewed 60 unilateral DBT studies (craniocaudal and medio-lateral oblique views). Trainees had no DBT experience. Each reader recorded a final BI RADS assessment for each case. The consensus interpretations from fellowship trained breast imagers were used to establish the ground truth. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated. For analysis, first- through third-year residents were classified as junior trainees, and fourth-year residents plus nonbreast imaging fellows were classified as senior trainees. RESULTS: The AUCs were .569 for medical students, .721 for junior trainees, .701 for senior trainees, and .792 for breast imaging fellows. The junior and senior trainee AUCs were equivalent (P < .01) using a two one-sided test for equivalence, with a significance threshold of 0.1. The sensitivities and specificities were highest for breast imaging fellows (.778 and .815 respectively), but similar for junior (.631 and .714, respectively) and senior trainees (.678 and .661, respectively). CONCLUSIONS: Initial performance with DBT among radiology residents and nonbreast imaging fellows is independent of years of training. Radiology educators should consider these findings when developing educational materials. PMID- 26143568 TI - The Time for Registry Participation Is Now. PMID- 26143569 TI - Learning to See. PMID- 26143570 TI - Prevalence and risk factors for pica during pregnancy in Tehran, Iran. AB - INTRODUCTION AND OBJECTIVES: Pica is an eating disorder characterized by the persistent ingestion of substances that the consumer does not define as food. The exact cause of pica is often unknown. The purpose of this study was to determine the prevalence of pica during pregnancy and its related risk factors. METHOD: This cross-sectional study was carried out in health care centers in west of Tehran. Three hundred women were selected by stratified sampling method from the population. Demographic information and characteristics of pica during pregnancy, such as the kind, the onset, duration, frequency and the reasons, and also iron supplementation status before and during pregnancy and kind of infant feeding were collected via interview and questionnaire. The data were analyzed by chi square test and logistic regression in SPSS 16. RESULTS: The prevalence of pica among the studied population was 8.33%, and pagophagia (ice and freezer frost) was the most common form of pica which is characterized by the ingestion of non food substance (76%). Sixty-four percent of women reported practicing pica regularly on a daily basis. In this study, there was significant association between pica practice and education, unwanted pregnancy, pregnancy complications, the levels of economic satisfaction, iron supplementation during pregnancy, kind of infant feeding, and type of delivery. However, there was no significant association between pica and age, employment, pregnancy ranks, the history of abortions or stillbirths, infant sex, and iron supplementation before pregnancy. CONCLUSIONS: Iron supplementation during pregnancy should be more considered. Also women with low education should be asked concerning pregnancy pica. PMID- 26143571 TI - Metacognitions about desire thinking predict the severity of binge eating in a sample of Italian women. AB - In this study, our principal aim was to investigate whether metacognitions about desire thinking predict the severity of binge eating in women and, if so, whether this relationship is independent of age, self-reported body mass index (BMI), negative affect, irrational food beliefs and craving. One hundred and four women, consisting of 32 consecutive patients with binge eating disorder undergoing initial assessment for cognitive therapy for eating disorders, 39 moderate binge eaters, and 33 non-binge eaters (both from the general population), completed the following measures: Self-reported BMI, Hospital Anxiety and Depression Scale, Irrational Food Beliefs Scale, General Craving Scale, Metacognitions about Desire Thinking Questionnaire, and Binge Eating Scale. A series of Spearman's rho correlation analyses revealed that self-reported BMI, anxiety, depression, irrational food beliefs, craving, and all three factors of the metacognitions about desire thinking questionnaire were significantly associated with the severity of binge eating. A stepwise regression analysis identified self-reported BMI, craving, and negative metacognitions about desire thinking as significant predictors of the severity of binge eating. These results, taken together, highlight the possible role of metacognitions about desire thinking in predicting the severity of binge eating. The clinical implications of these findings are discussed. PMID- 26143572 TI - Highly efficient rice straw utilization for poly-(gamma-glutamic acid) production by Bacillus subtilis NX-2. AB - Lignocellulosic biomass has been identified as an economic and environmental feedstock for future biotechnological production. Here, for the first time, poly (gamma-glutamic acid) (PGA) production by Bacillus subtilis NX-2 using rice straw is investigated. Based on two-stage hydrolysis and characteristic consumption of xylose and glucose by B. subtilis NX-2, a co-fermentation strategy was designed to better accumulate PGA in a 7.5L fermentor by two feeding methods. The maximum cumulative respective PGA production and PGA productivity were 73.0 +/- 0.5 g L( 1) and 0.81 g L(-1) h(-1) by the continuous feeding method, with carbon source cost was saved by 84.2% and 42.5% compared with glucose and cane molasse, respectively. These results suggest that rice straw, a type of abundant, low cost, non-food lignocellulosic feedstock, may be feasibly and efficiently utilized for industrial-scale production of PGA. PMID- 26143573 TI - Addition of crude glycerine as strategy to balance the C/N ratio on sewage sludge thermophilic and mesophilic anaerobic co-digestion. AB - The effect of adding crude glycerine during continuous sewage sludge anaerobic digestion was investigated under thermophilic and mesophilic temperatures. Addition of CGY at thermophilic temperature range showed a negative impact on stability and performance of the process, even at low doses. The extreme pH values of CGY, together with the rapid release of VFA, causes SS alkalinity fail to control pH drop. On the contrary, at mesophilic temperature range the process performs steadily, with 148% increase in methane production when CGY represented 1% v/v of the influent (27% of influent COD). Further CGY percentages did not show any added improvement; the biomass shift, due to a high C/N ratio, could explain this behaviour. Results suggested that CGY can be used as co-substrate of SS anaerobic digestion though, depending on the characteristics of CGY, and on operational conditions, different parameters should be taken into account to achieve a steady and consistent operation. PMID- 26143574 TI - Concurrent production of biodiesel and chemicals through wet in situ transesterification of microalgae. AB - This work addresses an unprecedented way of co-producing biodiesel (FAEE) and valuable chemicals of ethyl levulinate (EL), ethyl formate (EF) and diethyl ether (DEE) from wet in situ transesterification of microalgae. EL, EF, and DEE were significantly produced up to 23.1%, 10.3%, and 52.1% of the maximum FAEE mass with the FAEE yield higher than 90% at 125 degrees C. Experiments to elucidate a detailed route of EL and EF synthesis were fulfilled and it was found that its main route to the production of EL and EF was the acid hydrolysis of algal cells and esterification with ethanol. To investigate the effect of reaction variables on the products yields, comprehensive experiments were carried out with varying temperatures, solvent and alcohol volumes, moisture contents and catalyst amounts. Coproduction of DEE, EL, EF and FAEE can contribute to elevating the economic feasibility of microalgae-based biodiesel supply chain. PMID- 26143575 TI - Effects of Benzalkonium Chloride, Proxel LV, P3 Hypochloran, Triton X-100 and DOWFAX 63N10 on anaerobic digestion processes. AB - In this study, the individual and synergistic toxicity of the following xenobiotics: Benzalkonium Chloride (BKC), Proxel LV (PRX), P3 Hypochloran (HPC), Triton X-100 (TRX), and DOWFAX 63N10 (DWF), on anaerobic digestion (AD) process, was assessed. The experiments were performed in batch and continuous (up-flow anaerobic sludge blanket, UASB) reactors with biochemical-industrial wastewater, as substrate. In batch experiments, half-maximal inhibitory concentrations (IC50) for the tested xenobiotics were found to be 13.1, 1003, 311.5 and 24.3 mg L(-1) for BKC, PRX, DWF and TRX, respectively while HPC did not affect the AD process. Furthermore, the xenobiotics mixture tested did not present any synergistic inhibitory effect on the AD process. In continuous experiments, BKC and xenobiotics' mixture induced even stronger (more than 85%) of inhibition, expressed as IC50, compared to the levels observed from the batch reactors. Oppositely, TRX showed no inhibition in continuous mode, while inhibition was detected at batch mode. PMID- 26143576 TI - Laundering habits of student nurses and correlation with the presence of Staphylococcus aureus on nursing scrub tops pre- and postlaundering. AB - Little is known about student nurse laundering practices. Student nurses swabbed their scrub tops after clinical and after laundering, and they completed a laundry survey; 13.5% of students wore the same scrub more than once, and few followed recommended guidelines by using hot water (20%) or bleach (5.6%) when laundering scrubs. After clinical shifts, 17% of swabs tested positive for Staphylococcus aureus; however, laundering eradicated it from 64.3% of positive samples. This was not statistically significant. PMID- 26143577 TI - Esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. AB - INTRODUCTION: Esophageal diverticulum, a relatively rare condition, has been considered to be associated with motor abnormalities such as conditions that cause a lack of coordination between the distal esophagus and lower esophageal sphincter. PRESENTATION OF CASE: We herein report a case of esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. A 73-year-old woman presented with dysphagia and regurgitation. Imaging examinations revealed a right sided esophageal diverticulum located about 10cm above the esophagogastric junction. High-resolution manometry revealed normal esophageal motility. However, 24-h pH monitoring revealed continuous acidity due to pooling of residue in the diverticulum. An esophageal epiphrenic diverticulum was diagnosed and resected thoracoscopically. Her dysphagia recurred 2 years later. High-resolution manometry revealed diffuse esophageal spasm. DISCUSSION: The diverticulum in the present case was considered to have been associated with diffuse esophageal spasm. The motility disorder was likely not identified at the first evaluation. CONCLUSION: In this case, the patient's symptoms spontaneously resolved without any treatment; however, longer-term follow-up is needed. PMID- 26143578 TI - Perfumes of survival. PMID- 26143579 TI - Beliefs about the causes of obesity in a national sample of 4th year medical students. AB - OBJECTIVE: Physician knowledge of the complex contributors to obesity varies. We do not know whether today's medical students are graduating with deep understanding of the causes of obesity. Our objective was to assess beliefs about causes of obesity in a national sample of 4th year medical students. METHOD: We randomly selected 2000 4th year students from a random sample of 50 U.S. medical schools and asked them to rate the importance of several factors as causes of obesity. Of those invited, 1244 (62%) responded. We conducted latent class analysis to identify groups with similar response patterns. RESULTS: Most students demonstrated knowledge that obesity has multiple contributors. Students fell into 1 of 4 classes: (1) more likely to endorse all contributors (28%), (2) more likely to endorse physiological contributors (27%), (3) more likely to endorse behavioral or social contributors (24%), and (4) unlikely to endorse contributors outside of overeating and physical activity (22%). CONCLUSION: Though students were generally aware of multiple causes, there were 4 distinct patterns of beliefs, with implications for patient care. PRACTICE IMPLICATIONS: Targeted interventions may help to improve depth of knowledge about the causes of obesity and lead to more effective care for obese patients. PMID- 26143581 TI - Two new routes to make blood: Hematopoietic specification from pluripotent cell lines versus reprogramming of somatic cells. AB - Transplantation of hematopoietic stem cells (HSCs) to treat hematologic disorders is routinely used in the clinic. However, HSC therapy is hindered by the requirements of finding human leukocyte antigen (HLA)-matched donors and attaining sufficient numbers of long-term HSCs in the graft. Therefore, ex vivo expansion of transplantable HSCs remains one of the "holy grails" of hematology. Without the ability to maintain and expand human HSCs in vitro, two complementary approaches involving cellular reprogramming to generate transplantable HSCs have emerged. Reprogrammed HSCs represent a potentially inexhaustible supply of autologous tissue. On March 18th, 2015, Dr. George Q. Daley and Dr. Derrick J. Rossi, two pioneers in the field, presented and discussed their most recent research on these topics in a webinar organized by the International Society for Experimental Hematology (ISEH). Here, we summarize these seminars and discuss the possibilities and challenges in the field of hematopoietic specification. PMID- 26143583 TI - Very long-term survival in pancreatic cancer. PMID- 26143580 TI - Deconstructing innate immune signaling in myelodysplastic syndromes. AB - Overexpression of immune-related genes is widely reported in myelodysplastic syndromes (MDSs), and chronic immune stimulation increases the risk for developing MDS. Aberrant innate immune activation, such as that caused by increased toll-like receptor (TLR) signaling, in MDS can contribute to systemic effects on hematopoiesis, in addition to cell-intrinsic defects on hematopoietic stem/progenitor cell (HSPC) function. This review will deconstruct aberrant function of TLR signaling mediators within MDS HSPCs that may contribute to cell intrinsic consequences on hematopoiesis and disease pathogenesis. We will discuss the contribution of chronic TLR signaling to the pathogenesis of MDS based on evidence from patients and mouse genetic models. PMID- 26143584 TI - The development of a national HIV Plan in Belgium: Achieving consensus despite institutional complexity. AB - BACKGROUND: The development of a national HIV Plan poses serious challenges to countries with a complex distribution of legal powers such as Belgium. This article explores how the Belgian national HIV Plan 2014-2019 was developed. METHODS: Applying the policy streams model of John Kingdon, the analysis of the HIV Plan development process was based on published government statements, parliamentary documents, and websites of stakeholders. RESULTS: The Federal Ministry of Health initiative to achieve the HIV Plan was characterized by a coordinating role with a participatory approach towards the other Belgian governments and stakeholders. The 2013 protocol agreement of the Belgian governments committed them to principles, actions, and cooperation, but not to budgets, priorities, or target figures. DISCUSSION: The Federal government followed a successful strategy to create momentum and commitment to a common national vision on HIV/AIDS. The window of opportunity was not sufficient to create an implementation plan prior to the 2014 elections, and major challenges were left to the subsequent governments, including financing. CONCLUSION: The country of Belgium represents an example of a consensus strategy to achieve a national HIV Plan with its achievements and limits within institutional complexity and limited Federal legal powers. PMID- 26143582 TI - An international effort to cure a global health problem: A report on the 19th Hemoglobin Switching Conference. AB - Every 2 years since 1978, an international group of scientists, physicians, and other researchers meet to discuss the latest developments in the underlying etiology, mechanisms of action, and developmental acquisition of cellular and systemic defects exhibited and elicited by the most common inherited human disorders, the hemoglobinopathies. The 19th Hemoglobin Switching Conference, held in September 2014 at St. John's College in Oxford, once again exceeded all expectations by describing cutting edge research in cellular, molecular, developmental, and genomic advances focused on these diseases. The conference comprised about 60 short talks over 3 days by leading investigators in the field. This meeting report describes the highlights of the conference. PMID- 26143585 TI - An iterative deconvolution algorithm for image recovery in clinical CT: A phantom study. AB - PURPOSE: To study the feasibility of using an iterative reconstruction algorithm to improve previously reconstructed CT images which are judged to be non diagnostic on clinical review. A novel rapidly converging, iterative algorithm (RSEMD) to reduce noise as compared with standard filtered back-projection algorithm has been developed. MATERIALS AND METHODS: The RSEMD method was tested on in-silico, Catphan((r))500, and anthropomorphic 4D XCAT phantoms. The method was applied to noisy CT images previously reconstructed with FBP to determine improvements in SNR and CNR. To test the potential improvement in clinically relevant CT images, 4D XCAT phantom images were used to simulate a small, low contrast lesion placed in the liver. RESULTS: In all of the phantom studies the images proved to have higher resolution and lower noise as compared with images reconstructed by conventional FBP. In general, the values of SNR and CNR reached a plateau at around 20 iterations with an improvement factor of about 1.5 for in noisy CT images. Improvements in lesion conspicuity after the application of RSEMD have also been demonstrated. The results obtained with the RSEMD method are in agreement with other iterative algorithms employed either in image space or with hybrid reconstruction algorithms. CONCLUSIONS: In this proof of concept work, a rapidly converging, iterative deconvolution algorithm with a novel resolution subsets-based approach that operates on DICOM CT images has been demonstrated. The RSEMD method can be applied to sub-optimal routine-dose clinical CT images to improve image quality to potentially diagnostically acceptable levels. PMID- 26143586 TI - Feasibility of spectral CT imaging for the detection of liver lesions with gold based contrast agents - A simulation study. AB - PURPOSE: To demonstrate the feasibility of gold-specific spectral CT imaging for the detection of liver lesions in humans at low concentrations of gold as targeted contrast agent. METHODS: A Monte Carlo simulation study of spectral CT imaging with a photon-counting and energy-resolving detector (with 6 energy bins) was performed in a realistic phantom of the human abdomen. The detector energy thresholds were optimized for the detection of gold. The simulation results were reconstructed with the K-edge imaging algorithm; the reconstructed gold-specific images were filtered and evaluated with respect to signal-to-noise ratio and contrast-to-noise ratio (CNR). RESULTS: The simulations demonstrate the feasibility of spectral CT with CNRs of the specific gold signal between 2.7 and 4.8 after bilateral filtering. Using the optimized bin thresholds increases the CNRs of the lesions by up to 23% compared to bin thresholds described in former studies. CONCLUSIONS: Gold is a promising new CT contrast agent for spectral CT in humans; minimum tissue mass fractions of 0.2 wt% of gold are required for sufficient image contrast. PMID- 26143587 TI - Removal of Microcystis aeruginosa using cationic starch modified soils. AB - A cheap and biodegradable modifier, cationic starch (CS), was used to turn local soils into effective flocculants for Microcystis aeruginosa (M. aeruginosa) removal. The isoelectric point of soil particles was remarkably increased from pH 0.5 to 11.8 after modification with CS, which made CS modified soil particles positively charged and obtain algal flocculation ability. At the soil concentration of 100 mg/L, when the CS modifier was 10 mg/L, 86% of M. aeruginosa cells were removed within 30 min. Lower or higher CS dosage led to limited algal removal. About 71% and 45% of M. aeruginosa cells were removed within 30 min when CS was 5 mg/L and 80 mg/L, respectively. This is because only part of algal cells combined with CS modified soil particles through charge neutralization at low dosage, while flocs formed at high CS dosage were positively charged which prevents further aggregation among the flocs. The floc stability was quantified by a floc breakage index under applied shear force. Algal flocs formed at acid and alkaline conditions were more prone to be broken than those at the neutral condition. The cost and biodegradability concerns may be largely reduced through the use of CS modified local soils. For field applications, other practical issues (e.g., re-suspension) should be further studied by jointly using other methods. PMID- 26143588 TI - Roles of extracellular polymeric substances in enhanced biological phosphorus removal process. AB - Enhanced biological phosphorus removal (EBPR) process is known to mainly rely on the ability of phosphorus-accumulating organisms to take up, transform and store excess amount of phosphorus (P) inside the cells. However, recent studies have revealed considerable accumulation of P also in the extracellular polymeric substances (EPS) of sludge, implying a non-negligible role of EPS in P removal by EBPR sludge. However, the contribution of EPS to P uptake and the forms of accumulated extracellular P vary substantially in different studies, and the underlying mechanism of P transformation and transportation in EPS remains poorly understood. This review provides a new recognition into the P removal process in EBPR system by incorporating the role of EPS. It overviews on the characteristics of P accumulation in EPS, explores the mechanism of P transformation and transportation in EBPR sludge and EPS, summarizes the main influential factors for the P-accumulation properties of EPS, and discusses the remaining knowledge gaps and needed future efforts that may lead to better understanding and use of such an EPS role for maximizing P recovery from wastewater. PMID- 26143589 TI - Biological carbon dioxide utilisation in food waste anaerobic digesters. AB - Carbon dioxide (CO2) enrichment of anaerobic digesters (AD) was previously identified as a potential on-site carbon revalorisation strategy. This study addresses the lack of studies investigating this concept in up-scaled units and the need to understand the mechanisms of exogenous CO2 utilisation. Two pilot scale ADs treating food waste were monitored for 225 days, with the test unit being periodically injected with CO2 using a bubble column. The test AD maintained a CH4 production rate of 0.56 +/- 0.13 m(3) CH4.(kg VS(fed) d)(-1) and a CH4 concentration in biogas of 68% even when dissolved CO2 levels were increased by a 3 fold over the control unit. An additional uptake of 0.55 kg of exogenous CO2 was achieved in the test AD during the trial period. A 2.5 fold increase in hydrogen (H2) concentration was observed and attributed to CO2 dissolution and to an alteration of the acidogenesis and acetogenesis pathways. A hypothesis for conversion of exogenous CO2 has been proposed, which requires validation by microbial community analysis. PMID- 26143590 TI - Insights and clinical perspectives of daptomycin resistance in Staphylococcus aureus: A review of the available evidence. AB - The emergence of glycopeptide reduced susceptibility and resistance in Staphylococcus aureus strains is a growing clinical problem that poses significant clinical challenges in treatment. Its development is a complex and novel process involving many subtle physiological changes in the micro-organism. Daptomycin is the first cyclic lipopeptide approved for clinical use. Unlike most other antimicrobials, a trend towards increased daptomycin resistance has not been reported, although several cases of daptomycin non-susceptibility have been reported. The present review will present the available evidence on daptomycin resistance of S. aureus, with particular attention to its development. In addition to a literature overview, we have compiled the reported cases of daptomycin non-susceptibility to shed light on possible clinical mechanisms of resistance. In the 36 reports describing 62 clinical cases, infections caused by meticillin-resistant S. aureus (MRSA) strains with a vancomycin minimum inhibitory concentration (MIC) between 1mg/L and 2mg/L often led to vancomycin treatment failure, which may be associated with the development of non susceptibility to daptomycin. Additional evidence suggests that underdosage of daptomycin is an important clinical aspect that merits further study. The current analysis highlights the importance of determining the MIC when using vancomycin to treat patients with severe S. aureus infections and that when failure is suspected, testing for heterogeneous vancomycin-intermediate S. aureus (hVISA) may also be necessary. Whilst further investigation is needed, it can be hypothesised that MRSA strains become hVISA during prolonged bacteraemia, which may predispose to the development of daptomycin resistance. PMID- 26143591 TI - Ceftolozane/tazobactam and ceftazidime/avibactam: two novel beta-lactam/beta lactamase inhibitor combination agents for the treatment of resistant Gram negative bacterial infections. AB - The rise in resistant Gram-negative bacteria is a major concern and has led to difficulty in treating multidrug-resistant (MDR) infections. Two recently approved combination antibiotics, ceftolozane/tazobactam and ceftazidime/avibactam, may be effective in treating these resistant infections. Ceftolozane is a novel cephalosporin that has been developed in combination with tazobactam, a recognised beta-lactamase inhibitor (BLI). Avibactam is a novel BLI combined with ceftazidime, a cephalosporin with an established history. Both of these beta-lactam/BLI combination agents have been shown to retain in vitro activity against selected resistant Gram-negative pathogens, including Enterobacteriaceae and Pseudomonas aeruginosa; notably, ceftazidime/avibactam has demonstrated consistent activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms. Both agents have been approved for the indications of complicated intra-abdominal infection (with metronidazole) and complicated urinary tract infection, and have ongoing phase 3 trials for the treatment of ventilator-associated and nosocomial pneumonia. This manuscript will review current data available regarding the spectrum of activity and clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents. Both agents appear to be well tolerated and show promise in the treatment of MDR Gram-negative infections. PMID- 26143592 TI - Use of whole-genome sequencing for characterisation of a ST119 NDM-1-producing Acinetobacter pittii from a patient in Denmark with no history of recent travel. PMID- 26143593 TI - Short-term results of open inguinal hernia repair with self-gripping Parietex ProGrip mesh in China: A retrospective study of 90 cases. AB - OBJECTIVES: This study investigated short-term outcomes of Lichtenstein hernia repair using self-gripping Parietex ProGrip mesh in Chinese patients with inguinal hernias. METHODS: Retrospective analysis of patients undergoing Lichtenstein hernia repair using the Parietex ProGrip mesh at a single hospital in China between July 2012 and June 2013. All patients completed the EuroQol-five dimensions (EuroQoL-5D) and short form-36 questionnaires and were followed up at 1 day, 7 days, 1 month. and 6 months, postoperatively. RESULTS: Ninety cases (66 males, 24 females) were studied. Mean +/- standard deviation (SD) patient age was 48.7 +/- 16.8 (range, 21-87) years. Most hernias were Gilbert's type II (23%) or III (31%). During 6 months of follow-up, none of the patients had recurrent hernia or systemic postoperative complications. The mean +/- SD pain visual analog scale score decreased from 32 +/- 10.6 at postoperative Day 1 to 0.67 +/- 2.5 at 6 months. From postoperative Day 1 to 6 months, there were marked improvements in health and health-related quality of life; mean +/- SD visual analog scale EuroQoL score increased from 55.3 +/- 8 to 95.2 +/- 3 and mean +/- SD HR EuroQoL score from 0.31 +/- 0.07 to 0.95 +/- 0.02. At 6 months, mean scores in all eight dimensions of the short form-36 questionnaires had increased from baseline. CONCLUSION: The use of self-fixating Parietex ProGrip mesh in open inguinal hernia repair is simple, rapid, effective, and safe, and is associated with low postoperative pain and improved quality life among patients. PMID- 26143594 TI - Iterative optimization algorithm with parameter estimation for the ambulance location problem. AB - The emergency vehicle location problem to determine the number of ambulance vehicles and their locations satisfying a required reliability level is investigated in this study. This is a complex nonlinear issue involving critical decision making that has inherent stochastic characteristics. This paper studies an iterative optimization algorithm with parameter estimation to solve the emergency vehicle location problem. In the suggested algorithm, a linear model determines the locations of ambulances, while a hypercube simulation is used to estimate and provide parameters regarding ambulance locations. First, we suggest an iterative hypercube optimization algorithm in which interaction parameters and rules for the hypercube and optimization are identified. The interaction rules employed in this study enable our algorithm to always find the locations of ambulances satisfying the reliability requirement. We also propose an iterative simulation optimization algorithm in which the hypercube method is replaced by a simulation, to achieve computational efficiency. The computational experiments show that the iterative simulation optimization algorithm performs equivalently to the iterative hypercube optimization. The suggested algorithms are found to outperform existing algorithms suggested in the literature. PMID- 26143596 TI - The origin of cure for fistula in ano: technique of Hippocrates. PMID- 26143595 TI - A passage from India: Association between air traffic and reported cases of New Delhi Metallo-beta-lactamase 1 from 2007 to 2012. AB - BACKGROUND: Highly transmissible genes encoding resistance to carbapenems have demonstrated global spread. The New Delhi Metallo-beta-lactamase 1 gene is hypothesized to have originated in India, with subsequent dissemination by colonized or infected travelers. METHOD: We conducted an ecological study evaluating the association between the cumulative air traffic departing India between 2007 and 2012 and published cases of NDM-1. Receiver operator characteristic curves were generated as well as multivariate logistic regression models. 193 countries with complete flight and World Bank data were included in the analysis. RESULTS: Receiver operator characteristic curves (ROC) of the dichotomous outcome of a published case of NDM-1 were generated, yielding an unadjusted area under the curve (AUC) of 0.88 and adjusted AUC of 0.85. The unadjusted odds ratio of having a reported case of NDM-1, for every percentage increase in cumulative air traffic departing India, was 2.3 (95% CI 1.4 to 3.7) and adjusted was 2.0 (95% CI 1.2 to 3.4). CONCLUSIONS: We demonstrate that flows of international travelers departing India by air is associated with published NDM-1 cases, globally. Countries with high passenger flight traffic from India with no reported cases of NDM-1 may be at increased risk of having unreported transmission of NDM-1. PMID- 26143597 TI - The Influence of Polymorphisms in Disease Severity in beta-Thalassemia. AB - beta-Thalassemia is a genetic disorder with a continuum of mild to severe clinical manifestations and requirement of transfusion at different stages of life. The cause(s) of this variety is not clear but genetic alterations could be a potential factor. In this review, the correlation between polymorphisms and different clinical manifestations, including the need for transfusion, was investigated. Relevant articles published in pubmed database from 1982 onwards were studied and compiled. The articles all contained the keywords beta thalassemia, genetic modifiers, and mutations. Certain polymorphisms and mutations could dictate the severity of symptoms as well as their onset. A significant number of the mentioned genetic alterations appear in beta-globin gene cluster and affect gamma chain. Therefore, hemoglobin F production rate is increased and can affect thalassemia symptoms and can relieve beta-thalassemia symptoms. A number of polymorphisms in catalase and glutathione S transferase genes have also been shown to modify the severity of disease and response to treatment. Knowledge of these mutations and polymorphisms can provide an insight into the prognosis for individual patients, especially in young ages or before birth to take proper measures in advance and eventually ameliorate the symptoms in the long run. PMID- 26143598 TI - Beyond Descartes and Newton: Recovering life and humanity. AB - Attempts to 'naturalize' phenomenology challenge both traditional phenomenology and traditional approaches to cognitive science. They challenge Edmund Husserl's rejection of naturalism and his attempt to establish phenomenology as a foundational transcendental discipline, and they challenge efforts to explain cognition through mainstream science. While appearing to be a retreat from the bold claims made for phenomenology, it is really its triumph. Naturalized phenomenology is spearheading a successful challenge to the heritage of Cartesian dualism. This converges with the reaction against Cartesian thought within science itself. Descartes divided the universe between res cogitans, thinking substances, and res extensa, the mechanical world. The latter won with Newton and we have, in most of objective science since, literally lost our mind, hence our humanity. Despite Darwin, biologists remain children of Newton, and dream of a grand theory that is epistemologically complete and would allow lawful entailment of the evolution of the biosphere. This dream is no longer tenable. We now have to recognize that science and scientists are within and part of the world we are striving to comprehend, as proponents of endophysics have argued, and that physics, biology and mathematics have to be reconceived accordingly. Interpreting quantum mechanics from this perspective is shown to both illuminate conscious experience and reveal new paths for its further development. In biology we must now justify the use of the word "function". As we shall see, we cannot prestate the ever new biological functions that arise and constitute the very phase space of evolution. Hence, we cannot mathematize the detailed becoming of the biosphere, nor write differential equations for functional variables we do not know ahead of time, nor integrate those equations, so no laws "entail" evolution. The dream of a grand theory fails. In place of entailing laws, a post-entailing law explanatory framework is proposed in which Actuals arise in evolution that constitute new boundary conditions that are enabling constraints that create new, typically unprestatable, Adjacent Possible opportunities for further evolution, in which new Actuals arise, in a persistent becoming. Evolution flows into a typically unprestatable succession of Adjacent Possibles. Given the concept of function, the concept of functional closure of an organism making a living in its world, becomes central. Implications for patterns in evolution include historical reconstruction, and statistical laws such as the distribution of extinction events, or species per genus, and the use of formal cause, not efficient cause, laws. PMID- 26143599 TI - Why natural science needs phenomenological philosophy. AB - Through an exploration of theoretical physics, this paper suggests the need for regrounding natural science in phenomenological philosophy. To begin, the philosophical roots of the prevailing scientific paradigm are traced to the thinking of Plato, Descartes, and Newton. The crisis in modern science is then investigated, tracking developments in physics, science's premier discipline. Einsteinian special relativity is interpreted as a response to the threat of discontinuity implied by the Michelson-Morley experiment, a challenge to classical objectivism that Einstein sought to counteract. We see that Einstein's efforts to banish discontinuity ultimately fall into the "black hole" predicted in his general theory of relativity. The unavoidable discontinuity that haunts Einstein's theory is also central to quantum mechanics. Here too the attempt has been made to manage discontinuity, only to have this strategy thwarted in the end by the intractable problem of quantum gravity. The irrepressible discontinuity manifested in the phenomena of modern physics proves to be linked to a merging of subject and object that flies in the face of Cartesian philosophy. To accommodate these radically non-classical phenomena, a new philosophical foundation is called for: phenomenology. Phenomenological philosophy is elaborated through Merleau Ponty's concept of depth and is then brought into focus for use in theoretical physics via qualitative work with topology and hypercomplex numbers. In the final part of this paper, a detailed summary is offered of the specific application of topological phenomenology to quantum gravity that was systematically articulated in The Self-Evolving Cosmos (Rosen, 2008a). PMID- 26143600 TI - Self-reference, biologic and the structure of reproduction. AB - In this paper we explore the boundary shared by biology and formal systems. PMID- 26143601 TI - Influence of interfacial interactions on deformation mechanism and interface viscosity in alpha-chitin-calcite interfaces. AB - The interfaces between organic and inorganic phases in natural materials have a significant effect on their mechanical properties. This work presents a quantification of the interface stress as a function of interface chemical changes (water, organic molecules) in chitin-calcite (CHI-CAL) interfaces using classical non-equilibrium molecular dynamics (NEMD) simulations and steered molecular dynamics (SMD) simulations. NEMD is used to investigate interface stress as a function of applied strain based on the virial stress formulation. SMD is used to understand interface separation mechanism and to calculate interfacial shear stress based on a viscoplastic interfacial sliding model. Analyses indicate that interfacial shear stress combined with shear viscosity can result in variations to the mechanical properties of the examined interfacial material systems. It is further verified with Kelvin-Voigt and Maxwell viscoelastic analytical models representing viscous interfaces and outer matrix. Further analyses show that overall mechanical deformation depends on maximization of interface shear strength in such materials. This work establishes lower and upper bounds of interface strength in the interfaces examined. PMID- 26143602 TI - In-depth analysis of switchable glycerol based polymeric coatings for cell sheet engineering. AB - Scaffold-free cell sheet engineering using thermoresponsive substrates provides a promising alternative to conventional tissue engineering which in general employs biodegradable scaffold materials. We have previously developed a thermoresponsive coating with glycerol based linear copolymers that enables gentle harvesting of entire cell sheets. In this article we present an in-depth analysis of these thermoresponsive linear polyglycidyl ethers and their performance as coating for substrates in cell culture in comparison with commercially available poly(N isopropylacrylamide) (PNIPAM) coated culture dishes. A series of copolymers of glycidyl methyl ether (GME) and glycidyl ethyl ether (EGE) was prepared in order to study their thermoresponsive properties in solution and on the surface with respect to the comonomer ratio. In both cases, when grafted to planar surfaces or spherical nanoparticles, the applied thermoresponsive polyglycerol coatings render the respective surfaces switchable. Protein adsorption experiments on copolymer coated planar surfaces with surface plasmon resonance (SPR) spectroscopy reveal the ability of the tested thermoresponsive coatings to be switched between highly protein resistant and adsorptive states. Cell culture experiments demonstrate that these thermoresponsive coatings allow for adhesion and proliferation of NIH 3T3 fibroblasts comparable to TCPS and faster than on PNIPAM substrates. Temperature triggered detachment of complete cell sheets from copolymer coated substrates was accomplished within minutes while maintaining high viability of the harvested cells. Thus such glycerol based copolymers present a promising alternative to PNIPAM as a thermoresponsive coating of cell culture substrates. PMID- 26143603 TI - Sialic acid (SA)-modified selenium nanoparticles coated with a high blood-brain barrier permeability peptide-B6 peptide for potential use in Alzheimer's disease. AB - The blood-brain barrier (BBB) is a formidable gatekeeper toward exogenous substances, playing an important role in brain homeostasis and maintaining a healthy microenvironment for complex neuronal activities. However, it also greatly hinders drug permeability into the brain and limits the management of brain diseases. The development of new drugs that show improved transport across the BBB represents a promising strategy for Alzheimer's disease (AD) intervention. Whereas, previous study of receptor-mediated endogenous BBB transport systems has focused on a strategy of using transferrin to facilitate brain drug delivery system, a system that still suffers from limitations including synthesis procedure, stability and immunological response. In the present study, we synthetised sialic acid (SA)-modified selenium (Se) nanoparticles conjugated with an alternative peptide-B6 peptide (B6-SA-SeNPs, a synthetic selenoprotein analogue), which shows high permeability across the BBB and has the potential to serve as a novel nanomedicine for disease modification in AD. Laser-scanning confocal microscopy, flow cytometry analysis and inductively coupled plasma-atomic emission spectroscopy ICP-AES revealed high cellular uptake of B6-SA-SeNPs by cerebral endothelial cells (bEnd.3). The transport efficiency of B6-SA-SeNPs was evaluated in a Transwell experiment based on in vitro BBB model. It provided direct evidence for B6-SA-SeNPs crossing the BBB and being absorbed by PC12 cells. Moreover, inhibitory effects of B6-SA-SeNPs on amyloid-beta peptide (Abeta) fibrillation could be demonstrated in PC12 cells and bEnd3 cells. B6-SA-SeNPs could not only effectively inhibit Abeta aggregation but could disaggregate preformed Abeta fibrils into non-toxic amorphous oligomers. These results suggested that B6-SA-SeNPs may provide a promising platform, particularly for the application of nanoparticles in the treatment of brain diseases. STATEMENT OF SIGNIFICANCE: Alzheimer's disease (AD) is the world's most common form of dementia characterized by intracellular neurofibrillary tangles in the brain. Over the past decades, the blood-brain barrier (BBB) limits access of therapeutic or diagnostic agents into the brain, which greatly hinders the development of new drugs for treating AD. In this work, we evaluated the efficiency of B6-SA-SeNPs across BBB and investigated the interactions between B6-SA-SeNPs and amyloid-beta peptide (Abeta). We confirm that B6-SA-SeNPs could provide a promising platform because of its high brain delivery efficiency, anti-amyloid properties and anti-oxidant properties, which may serve as a novel nanomedicine for the application in the treatment of brain diseases. PMID- 26143604 TI - The role of ROS generation from magnetic nanoparticles in an alternating magnetic field on cytotoxicity. AB - Monosaccharide coated iron oxide nanoparticles were developed to selectively target colon cancer cell lines for magnetically mediated energy delivery therapy. The nanoparticles were prepared using a coupling reaction to attach the glucose functional group to the iron oxide core, and functionality was confirmed with physicochemical characterization techniques. The targeted nanoparticles were internalized into CT26 cells at a greater extent than non-targeted nanoparticles, and the nanoparticles were shown to be localized within lysosomes. Cells with internalized nanoparticles were exposed to an AMF to determine the potential to delivery therapy. Cellular ROS generation and apoptotic cell death was enhanced with field exposure. The nanoparticle coatings inhibit the Fenton-like surface generation of ROS suggesting a thermal or mechanical effect is more likely the source of the intracellular effect, unless the nanoparticle coating is unstable in the cellular environment. STATEMENT OF SIGNIFICANCE: This is the first study to assess glucose coated MNPs for the delivery of MagMED therapy. With exposure of an AMF, the glucose-coated nanoparticles displayed a significant increase in cellular ROS and apoptotic cell death with no measurable increase in media temperature. To determine the mechanism of toxicity, we investigated the surface generation of ROS through Fenton-like chemistry. The coated systems displayed negligible ROS generation compared to uncoated nanoparticles. These observations suggest the cellular ROS measured is attributed to a thermal or mechanical effect of the internalized nanoparticles. In summary, this manuscript reports on some new insights as to the mechanism of MagMED therapies, which are of high interest to the biomaterials and cancer nanomedicine fields. PMID- 26143605 TI - The effect of mechanical bowel preparation on anastomotic leaks in elective left sided colorectal resections. AB - BACKGROUND: Routine preoperative mechanical bowel preparation (MBP) for left sided colorectal resections remains controversial. This study aims to evaluate the association between MBP and 30-day anastomotic leaks. METHODS: A retrospective cohort study was conducted using data from the National Surgical Quality Improvement Program from 2011 to 2012. Multiple imputation was used for missing data, and a multivariable logistic regression was performed to adjust for clinically relevant variables. A propensity score-adjusted model was performed as a sensitivity analysis. RESULTS: A total of 2,581 patients (57%) received preoperative MBP, whereas 1,935 (43%) did not. The 30-day anastomotic leak rate with and without preoperative MBP was 3.1% and 5.1%, respectively. After covariate adjustment, MBP omission was significantly associated with a 40% increased odds of 30-day anastomotic leaks (odds ratio 1.41, P = .04, 95% confidence interval 1.01 to 1.93). CONCLUSIONS: MBP omission was associated with a higher rate of 30-day anastomotic leaks. A large, well-designed, randomized controlled trial is needed to further evaluate this relationship. PMID- 26143606 TI - Short-column anion-exchange chromatography for soil and peat humic substances profiling by step-wise gradient of high pH aqueous sodium ethylenediaminetetraacetate. AB - Novel anion-exchange liquid chromatographic method with step gradient of aqueous EDTA(4-) based mobile phase elution has been developed to profile available Slovak soil humic substances and alkaline extracts of various soils. The method utilize short glass column (30mm*3mm) filled in with hydrolytically stable particles (60MUm diameter) Separon HEMA-BIO 1000 having (diethylamino)ethyl functional groups. Step gradient was programmed by mixing mobile phase composed of aqueous solution of sodium EDTA (pH 12.0; 5mmolL(-1)) and mobile phase constituted of aqueous solution of sodium EDTA (pH 12.0, 500mmolL(-1)). The FLD of HSs was set to excitation wavelength 480nm and emission wavelength 530nm (lambdaem). Separation mechanism was studied by use of selected aromatic acids related to humic acids with the aid of UV spectrophotometric detection at 280nm. The proposed method benefits from high ionic strength (I=5molL(-1)) of the end mobile phase buffer and provides high recovery of humic acids (98%). Accurate and reproducible profiling of studied humic substances, alkaline extracts of various types of soils enables straightforward characterization and differentiation of HSs in arable and forest soils. Selected model aromatic acids were used for separation mechanism elucidation. PMID- 26143607 TI - Large-scale qualitative and quantitative characterization of components in Shenfu injection by integrating hydrophilic interaction chromatography, reversed phase liquid chromatography, and tandem mass spectrometry. AB - It is of great importance to clarify in depth the chemical composition, including qualitative and quantitative aspects, of traditional Chinese medicine (TCM) injection that contains a great number of hydrophilic and hydrophobic ingredients to guarantee its safe medication in clinic. Column-switching hydrophilic interaction liquid chromatography-reversed phase liquid chromatography coupled with tandem mass spectrometry (HILIC-RPLC-MS/MS) has been revealed to be advantageous at simultaneous measurement of compounds covering a broad polarity range. Previous studies have profiled the hydrophobic components, mainly aconite alkaloids and ginsenosides, in Shenfu Injection (SFI); however, the hydrophilic substances haven't been taken into account. In the present study, we aim to holistically characterize the hydrophilic constituents and to simultaneously quantitate both hydrophilic and hydrophobic components in SFI. A strategy integrating predefined multiple reaction monitoring, step-wise multiple ion monitoring, and enhanced product ion scans was proposed to universally screen the hydrophilic substances using a hybrid triple quadrupole-linear ion trap mass spectrometer. Structural identification was carried out by comparing with authentic compounds, analyzing MS(2) spectra, and referring to accessible databases (e.g., MassBank, METLIN and HMDB). A total of 157 hydrophilic compounds were detected from SFI, and 154 ones were identified as amino acids, nucleosides, organic acid, carbohydrates, etc. A column-switching HILIC-RPLC-MS/MS system was developed and validated for simultaneously quantitative analysis of 40 primary hydrophilic and hydrophobic ingredients in SFI, including eleven amino acids, nine nucleosides, nine aconite alkaloids, and eleven ginsenosides. Taken together, the findings obtained could provide meaningful information for comprehensively understanding the chemical composition and offer a reliable approach for the quality control of SFI. PMID- 26143608 TI - Experimental characterization of the transport phenomena, adsorption, and elution in a protein A affinity monolithic medium. AB - A commercially available convective interaction media (CIM) Protein A monolithic column was fully characterized in view of its application for the affinity capture of IgG in monoclonal antibody production processes. By means of moment analysis, the interstitial porosity and axial dispersion coefficient were determined. The frontal analysis method of characteristic points was employed, for the first time with monolithic media, to determine the dynamic binding capacity. The effects of the flow rate and pH on the total recovery of polyclonal IgG and elution profile were evaluated. A comparison with literature data for Protein A chromatography beads demonstrate the superior bed utilization of monolithic media, which gave better performance at lower residence times. PMID- 26143609 TI - Evaluation of 4 Different Irrigating Systems for Apical Extrusion of Sodium Hypochlorite. AB - INTRODUCTION: The aim of this study was to evaluate NaOCl apical extrusion by using negative apical pressure (EndoVac), sonic agitation (EndoActivator), side vented needle (Max-i-Probe), and photon induced photoacoustic streaming (PIPS 10 mJ and PIPS 20 mJ) laser irrigation in an in vitro gel model. METHODS: Extracted mandibular and maxillary central incisors (n = 18) were prepared to size 35/.04 and 55/.04, respectively. Teeth were mounted in transparent containers with clear acrylic and suspended in a color-changing pH-sensitive gel, creating a closed system. By using a crossover design, each tooth was sequentially irrigated by using 6% NaOCl with each device following manufacturers' recommendations. Each tooth served as its own control. Pre-irrigation and post-irrigation buccal and proximal view photographs served to measure the longest distance of extrusion and were analyzed with ImageJ software. Mean results were analyzed by using Kruskal Wallis and Dunn post hoc test (P < .05). RESULTS: There were no significant differences between EndoVac, EndoActivator, and the passive extrusion groups. The EndoVac and EndoActivator groups produced significantly less extrusion than PIPS irrigation. Max-i-Probe extrusion results were more variable than those of EndoActivator but had no significant difference. Across all irrigation systems, there were no significant differences with respect to apical preparation size. CONCLUSIONS: Under the in vitro conditions of this study, no difference was found between the 10 mJ and 20 mJ PIPS laser groups. EndoVac demonstrated significantly less potential for apical extrusion than PIPS and Max-i-Probe, whereas apical preparation size did not significantly affect extrusion of irrigant. The potential for apical extrusion of endodontic irrigants should be a consideration when selecting a system for final irrigation. PMID- 26143610 TI - A new mathematical model for nitrogen gas production with special emphasis on the role of attached growth media in anammox hybrid reactor. AB - The present study emphasised on the development of new mathematical models based on mass balance and stoichiometry of nitrogen removal in anammox hybrid reactor (AHR). The performance of AHR at varying hydraulic retention times (HRTs) and nitrogen loading rates (NLRs) revealed that nitrogen removal efficiency (NRE) increases with increase in HRT and was found optimal (89 %) at HRT of 2 days. Mass balance of nitrogen revealed that major fraction (74.1 %) of input nitrogen is converted into N2 gas followed by 11.2 % utilised in biomass synthesis. Attached growth media (AGM) in AHR contributed to an additional 15.4 % ammonium removal and reduced the sludge washout rate by 29 %. This also enhanced the sludge retention capacity of AHR and thus minimised the formation of nitrate in the treated effluent, which is one of the bottlenecks of anammox process. Process kinetics was also studied using various mathematical models. The mass balance model derived from total nitrogen was found most precise and predicted N2 gas with least error (1.68 +/- 4.44 %). Model validation for substrate removal kinetics dictated comparatively higher correlation for Grau second-order model (0.952) than modified Stover-Kincannon model (0.920). The study concluded that owing to features of high biomass retention, less nitrate formation and consistently higher nitrogen removal efficiency, this reactor configuration is techno-economically most efficient and viable. The study opens the door for researchers and scientists for pilot-scale testing of AHR leading to its wide industrial application. PMID- 26143611 TI - Estimating the contribution of influenza to hospitalisations in New Zealand from 1994 to 2008. AB - BACKGROUND: Influenza has a substantially but poorly measured impact on population health. Estimating its true contribution to hospitalisations remains a challenge. METHODS: We used simple and comprehensive negative binomial regression models with weekly counts of hospitalisations and isolates of influenza A, B and respiratory syncytial virus for the period 1994- 2008. RESULTS: The estimated annual national average number of hospitalisations attributable to influenza was 822.1(95% CI: 815.3, 828.9) for pneumonia and influenza, 1861.3 (95% CI: 1842.9, 1879.7) for respiratory illness, 12.1 (95% CI: 2.6, 21.6) for circulatory illness, 2260.0 (95% CI: 2212.2, 2307.8) for all medical illness and 2419.9 (95% CI: 2356.4, 2483.4) for all causes. The contribution of influenza to total hospitalisations was about nine times larger than indicated by routine discharge data. New Zealanders 80 years of age and older had the highest annual excess rates of influenza-related hospitalisations (327.8 per 100,000); followed by infants under 1 year (244.5 per 100,000). Estimated influenza hospitalisation rates were also markedly higher in Pacific (83.3 per 100,000) and Maori (80.0 per 100,000) compared with European/Others (58.1 per 100,000). Respiratory illness was the major contributor to all cause hospitalisations attributed to influenza accounting for 77%. Influenza hospitalisations included only a negligible contribution from circulatory illness. CONCLUSION: These findings support efforts to reduce the impact of influenza, particularly for the most vulnerable population groups highlighted here. Analysis of the cost-effectiveness of such interventions needs to consider these higher modelled estimates of disease impact. PMID- 26143612 TI - A model of health care provider decision making about HPV vaccination in adolescent males. AB - INTRODUCTION: In the U.S., HPV vaccination of adolescent males remains low, despite the recommendation for routine vaccination. Although research has highlighted that health care provider (HCP) recommendation is very influential in HPV vaccine uptake, research on this topic in the male population is lacking. Accordingly, we used a qualitative approach to identify HCP knowledge, attitudes, and behaviors regarding adolescent male HPV vaccination, one year, after routine vaccination of adolescent males was recommended. METHOD: A total of 20 U.S. pediatric HCPs participated in 20-30 min interviews about knowledge, attitudes, and practices regarding male HPV vaccination. Interviews were audio-recorded, transcribed and, analyzed using inductive content analysis. RESULTS: The providers had been in practice for 1-35 years, 75% were female, and 75% were White. Opinions on HPV vaccination were shaped by knowledge/perception of the risks and benefits of vaccination. Although all providers frequently offered HPV vaccine to male patients, the strength and content of the offer varied greatly. Vaccination opinions determined what issues were emphasized in the vaccine offer (e.g., stressing herd immunity, discussing prevention of genital warts), while adolescent age influenced if and how they pitched their vaccine offer (e.g., HPV as a STI). Most providers agreed with the ACIP recommendations, however, several expressed that providers' preexisting opinions might remain unchanged despite the recommendations. Consistent with the literature on determinants of HPV vaccination, providers believed that their own recommendation was a major factor in a family's decision to vaccinate. Barriers to vaccination included the "newness" and sexual nature of the vaccine, lack of insurance coverage, and the vaccine not being mandated. CONCLUSIONS: Providers' opinions about, and approaches to offering, HPV vaccination to males were highly variable. Interventions designed to improve male HPV vaccination should focus on helping providers to routinely recommend the vaccine to all of their eligible patients, both males and females. PMID- 26143614 TI - Report of the 2014 Cent Gardes HIV Vaccine Conference-Part 2: Cell-mediated immunity, mucosal protection, and clinical trials: Fondation Merieux Conference Center, Veyrier du Lac, France, 5-7 October, 2014. AB - The 2014 Cent Gardes Conference took place on October 5-7, 2014, at the Fondation Merieux Conference Center, on the shores of the Annecy Lake and aimed to review the progress and promise of HIV vaccines. The elicitation of broadly neutralizing antibodies (bNAbs), their use in passive immunization, as well as their genetic delivery (vector immunoprophylaxis) by a recombinant Adenovirus-associated virus (AAV) vector were reviewed in a preceding article [1]. Approaches to the elicitation of long-lasting T cell or mucosal immunity were also discussed and are now reviewed here. The possibility of eliciting mucosal IgAs was discussed, since it was demonstrated that transcytosis-blocking IgAs can protect monkeys against repeated vaginal challenge with a pathogenic chimeric simian and human immunodeficiency virus (SHIV). The possibility of purging the HIV reservoirs from HIV-infected persons and developing a cure of the disease was also discussed. PMID- 26143613 TI - Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naive subjects. AB - BACKGROUND: Modified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1*10(8) TCID50 in a volume of 0.5mL. This study compared the safety and immunogenicity of the standard formulation, dose and route with both a more stable, lyophilized formulation and with an antigen-sparing intradermal (ID) route of administration. METHODS: 524 subjects were randomized to receive either a full dose of Lyophilized-SC, a full dose of Liquid-SC or 20% (2*10(7) TCID50 in 0.1mL) of a full dose Liquid-ID MVA on Days 0 and 28. Safety and immunogenicity were followed through 180 days post second vaccination. RESULTS: Among the 3 groups, the proportion of subjects with moderate/severe functional local reactions was significantly different (P=0.0013) between the Lyophilized-SC group (30.3%), the Liquid-SC group (13.8%) and Liquid-ID group (22.0%) only after first vaccination; and for moderate/severe measured erythema and/or induration after any vaccination (P=0.0001) between the Lyophilized-SC group (58.2%), the Liquid-SC group (58.1%) and the Liquid-ID group (94.8%) and the reactions lasted longer in the Liquid-ID group. In the ID Group, 36.1% of subjects had mild injection site skin discoloration lasting >=6 months. After second vaccination Day (42-208), geometric mean of peak neutralization titers were 87.8, 49.5 and 59.5 for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively, and the maximum number of responders based on peak titer in each group was 142/145 (97.9%), 142/149 (95.3%) and 138/146 (94.5%), respectively. At 180 days after the second vaccination, geometric mean neutralization titers declined to 11.7, 10.2 and 10.4 with only 54.3%, 39.2% and 35.2% of subjects remaining seropositive for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively. Both the Lyophilized-SC and Liquid-ID groups were considered non-inferior (primary objective) to the Liquid-SC group. CONCLUSIONS: Transitioning to a lyophilized formulation, which has a longer shelf life, will not negatively impact immunogenicity. In a situation where insufficient vaccine is available, ID vaccination could be used, increasing the number of available doses of vaccine in the SNS 5-fold (i.e., from 20 million to 100 million doses). PMID- 26143615 TI - Safety and immunogenicity of a trivalent recombinant PcpA, PhtD, and PlyD1 pneumococcal protein vaccine in adults, toddlers, and infants: A phase I randomized controlled study. AB - BACKGROUND: Pneumococcal protein vaccines (PPrVs) may provide improved protection over currently available polysaccharide and conjugated polysaccharide vaccines. Here, we examined the safety and immunogenicity of a trivalent recombinant PPrV containing PcpA, PhtD, and PlyD1. METHODS: This was a phase I, single-center, randomized, observer-blind study with safety review between cohorts. Adults (18 50 years; n=30) and then toddlers (12-13 months; n=30) were randomized 2:1 to receive aluminum-adjuvanted trivalent PPrV (PPrV + adj) containing 50 MUg per antigen or placebo. Infants (42-49 days; n=220) were next randomized to be injected at 6, 10, and 14 weeks of age with 10 MUg PPrV + adj or placebo (n=60; 2:1); 25 MUg PPrV + adj, 25 MUg unadjuvanted PPrV, or placebo (n=100; 2:2:1); and 50 MUg PPrV + adj or placebo (n=60; 2:1). Solicited reactions were recorded for 7 days and unsolicited adverse events for 30 days after each vaccination. Concentrations of antibodies to the three vaccine antigens were measured by enzyme-linked immunosorbent assay. RESULTS: Tenderness/pain was the most frequent injection-site reaction. Abnormal crying and irritability (infants), loss of appetite (toddlers), and headache, malaise, and myalgia (adults) were the most frequent systemic reactions. Reactions were mostly mild or moderate, resolved within 3 days, were not adjuvant- or dose-dependent, and were not increased by repeated vaccination. No immediate adverse events, hypersensitivity reactions, or treatment-related serious adverse events were reported. In all PPrV + adj cohorts, at least 75% of subjects had a >=2-fold increase in all three antibody concentrations. In infants, antibody concentrations were higher with PPrV + adj than with unadjuvanted PPrV, higher with three than two vaccinations, and similar at the different vaccine doses. CONCLUSIONS: The candidate trivalent PPrV was safe and immunogenic in adults, toddlers, and infants. Addition of aluminum adjuvant improved immunogenicity in infants without changing the safety profile. PMID- 26143616 TI - Inhibition of GSK3beta rescues hippocampal development and learning in a mouse model of CDKL5 disorder. AB - Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in a rare neurodevelopmental disorder characterized by early-onset seizures, severe developmental delay, intellectual disability and Rett syndrome like features. CDKL5 is highly expressed in the brain during early postnatal stages, suggesting its importance for brain maturation. Using a newly-generated Cdkl5 knockout (Cdkl5 -/Y) mouse, we recently found that loss of Cdkl5 impairs postnatal hippocampal development with a reduction in neuronal precursor survival and maturation. These defects were accompanied by increased activity of the glycogen synthase kinase 3beta (GSK3beta) a crucial inhibitory regulator of many neurodevelopmental processes. The goal of the current study was to establish whether inhibition of GSK3beta corrects hippocampal developmental defects due to Cdkl5 loss. We found that treatment with the GSK3beta inhibitor SB216763 restored neuronal precursor survival, dendritic maturation, connectivity and hippocampus dependent learning and memory in the Cdkl5 -/Y mouse. Importantly, these effects were retained one month after treatment cessation. At present, there are no therapeutic strategies to improve the neurological defects of subjects with CDKL5 disorder. Current results point at GSK3beta inhibitors as potential therapeutic tools for the improvement of abnormal brain development in CDKL5 disorder. PMID- 26143618 TI - Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters. AB - This work investigates the suitability of the rainbow trout liver cell line (RTL W1) as an in-vitro model to study the ability of model endocrine disrupters, namely TBT, TPT, 4-NP, BPA and DEHP, to act as metabolic disrupters by altering cellular lipids and markers of lipid metabolism. Among the tested compounds, BPA and DEHP significantly increased the intracellular accumulation of triacylglycerols (TAGs), while all the compounds -apart from TPT-, altered membrane lipids - phosphatidylcholines (PCs) and plasmalogen PCs - indicating a strong interaction of the toxicants with cell membranes and cell signaling. RTL W1 expressed a number of genes involved in lipid metabolism that were modulated by exposure to BPA, TBT and TPT (up-regulation of FATP1 and FAS) and 4-NP and DEHP (down-regulation of FAS and LPL). Multiple and complex modes of action of these chemicals were observed in RTL-W1 cells, both in terms of expression of genes related to lipid metabolism and alteration of cellular lipids. Although further characterization is needed, this might be a useful model for the detection of chemicals leading to steatosis or other diseases associated with lipid metabolism in fish. PMID- 26143617 TI - Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings. AB - BACKGROUND AND OBJECTIVES: Severe infection with avian influenza A (H5N6) virus in humans was identified first in 2014 in China. Before that, it was unknown or unclear if the disease or the pathogen affected people. This study illustrates the virological and clinical findings of a fatal H5N6 virus infection in a human patient. METHODS: We obtained and analyzed the clinical, epidemiological, and virological data from the patient. Reverse transcription polymerase chain reaction (RT-PCR), viral culture, and sequencing were conducted for determination of the causative pathogen. RESULTS: The patient, who presented with fever, severe pneumonia, leucopenia, and lymphopenia, developed septic shock and acute respiratory distress syndrome (ARDS), and died on day 10 after illness onset. A novel reassortant avian-origin influenza A (H5N6) virus was isolated from the throat swab or trachea aspirate of the patient. The virus was reassorted with the HA gene of clade 2.3.4.4 H5, the internal genes of clade 2.3.2.1 H5, and the NA gene of the H6N6 avian virus. The cleavage site of the HA gene contained multiple basic amino acids, indicating that the novel H5N6 virus was highly pathogenic in chicken. CONCLUSIONS: A novel, highly pathogenic avian influenza H5N6 virus with a backbone of H5N1 virus acquired from the NA gene from the H6N6 virus has been identified. It caused human infection resulting in severe respiratory disease. PMID- 26143619 TI - Parent-offspring transaction: Mechanisms and the value of within family designs. AB - This article is part of a Special Issue "Parental Care". Parenting is best understood as a transactional process between parents and their offspring. Each responds to cues in the other, adapting their own behavior to that of their partner. One of the goals of parenting research in the past twenty years has been to untangle reciprocal processes between parents and children in order to specify what comes from the child (child effects) and what comes from the parent (parent effects). Child effects have been found to relate to genetic, pre and perinatal, family-wide, and child-specific environmental influences. Parent effects relate to stresses in the current context (e.g. financial strain, marital conflict), personality and ethnicity but also to adverse childhood experiences (e.g. parental mental health and substance abuse, poverty, divorce). Rodent models have allowed for the specification of biological mechanisms in parent and child effects, including neurobiological and genomic mechanisms, and of the causal role of environmental experience on outcomes for offspring through random assignment of offspring-mother groupings. One of the methods that have been developed in the human and animal models to differentiate between parent and child effects has been to study multiple offspring in the family. By holding the parent steady, and studying different offspring, we can examine the similarities and differences in how parents parent multiple offspring. Studies have distinguished between family average parenting, child-specific parenting and family-wide dispersion (the within family standard deviation). These different aspects of parenting have been differentially linked to offspring behavioral phenotypes. PMID- 26143620 TI - Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior. AB - Interleukin-6 (IL-6) is a major cytokine in the central nervous system, secreted by different brain cells and with roles in a number of physiological functions. We herewith confirm and expand the importance of astrocytic production of and response to IL-6 by using transgenic mice deficient in astrocytic IL-6 (Ast-IL-6 KO) or in its receptor (Ast-IL-6R KO) in full C57Bl/6 genetic background. A major prosurvival effect of astrocytic IL-6 at early ages was clearly demonstrated. Robust effects were also evident in the control of activity and anxiety in the hole-board and elevated plus-maze, and in spatial learning in the Morris water maze. The results also suggest an inhibitory role of IL-6 in the mechanism controlling the consolidation of hippocampus-dependent spatial learning. Less robust effects of astrocytic IL-6 system were also observed in despair behavior in the tail suspension test, and social behavior in the dominance and resident intruder tests. The behavioral phenotype was highly dependent on age and/or sex in some cases. The phenotype of Ast-IL-6R KO mice mimicked only partially that of Ast-IL-6KO mice, which indicates both a role of astrocytes in behavior and the participation of other cells besides astrocytes. No evidences of altered function of the hypothalamic-pituitary-adrenal axis were observed. These results demonstrate that astrocytic IL-6 (acting at least partially in astrocytes) regulates normal behavior in mice. PMID- 26143622 TI - Processing emotional words in two languages with one brain: ERP and fMRI evidence from Chinese-English bilinguals. AB - Emotional words in a bilingual's second language (L2) seem to have less emotional impact compared to emotional words in the first language (L1). The present study examined the neural mechanisms of emotional word processing in Chinese-English bilinguals' two languages by using both event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI). Behavioral results show a robust positive word processing advantage in L1 such that responses to positive words were faster and more accurate compared to responses to neutral words and negative words. In L2, emotional words only received higher accuracies than neutral words. In ERPs, positive words elicited a larger early posterior negativity and a smaller late positive component than neutral words in L1, while a trend of reduced N400 component was found for positive words compared to neutral words in L2. In fMRI, reduced activation was found for L1 emotional words in both the left middle occipital gyrus and the left cerebellum whereas increased activation in the left cerebellum was found for L2 emotional words. Altogether, these results suggest that emotional word processing advantage in L1 relies on rapid and automatic attention capture while facilitated semantic retrieval might help processing emotional words in L2. PMID- 26143623 TI - Biomarkers in multiple sclerosis. AB - Substantial effort has been made over the last six decades to identify biomarkers for multiple sclerosis that can improve disease diagnosis, predict disease progression, and improve clinical outcomes. However, to date, few of these findings have proven clinically useful. In this review, we address the current state of MS biomarker research. We start by discussing biomarkers currently in clinical use including Oligoclonal bands, MRI, and JC viral titers. We go on to discuss other potential biomarkers from MS serum and cerebrospinal fluid including Markers of neurodegeneration including neurofilament and GFAP, the monocyte macrophage marker CD163, the glial activation marker YKL-40, the B cell chemoattractant CXCL13, miRNA and mRNA, myelin reactive t cells, Kir4.1 antibodies, osteopontin, and microbiome associated lipopeptides. Finally, we discuss the current state of MS genetic studies and how genetics may offer simple, reliable testing for MS susceptibility and progression. PMID- 26143624 TI - The UK plastic surgery sentinel lymph node biopsy service in stage 1B cutaneous melanoma. PMID- 26143621 TI - Utilizing induced pluripotent stem cells (iPSCs) to understand the actions of estrogens in human neurons. AB - This article is part of a Special Issue "Estradiol and Cognition". Over recent years tremendous progress has been made towards understanding the molecular and cellular mechanism by which estrogens exert enhancing effects on cognition, and how they act as a neuroprotective or neurotrophic agent in disease. Currently, much of this work has been carried out in animal models with only a limited number of studies using native human tissue or cells. Recent advances in stem cell technology now make it possible to reprogram somatic cells from humans into induced pluripotent stem cells (iPSCs), which can subsequently be differentiated into neurons of specific lineages. Importantly, the reprogramming of cells allows for the generation of iPSCs that retain the genetic "makeup" of the donor. Therefore, it is possible to generate iPSC-derived neurons from patients diagnosed with specific diseases, that harbor the complex genetic background associated with the disorder. Here, we review the iPSC technology and how it's currently being used to model neural development and neurological diseases. Furthermore, we explore whether this cellular system could be used to understand the role of estrogens in human neurons, and present preliminary data in support of this. We further suggest that the use of iPSC technology offers a novel system to not only further understand estrogens' effects in human cells, but also to investigate the mechanism by which estrogens are beneficial in disease. Developing a greater understanding of these mechanisms in native human cells will also aid in the development of safer and more effective estrogen-based therapeutics. PMID- 26143625 TI - Glucose monomycolates based on single synthetic mycolic acids. AB - The preparation of 6-O-mycolylglucoses (GMMs) from single synthetic mycolic acids matching the overall structure of some of the major natural glucose monomycolates of Mycobacterium tuberculosis and other mycobacteria is reported. PMID- 26143626 TI - High-glucose diets have sex-specific effects on aging in C. elegans: toxic to hermaphrodites but beneficial to males. AB - Diet and sex are important determinants of lifespan. In humans, high sugar diets, obesity, and type 2 diabetes correlate with decreased lifespan, and females generally live longer than males. The nematode Caenorhabditis elegans is a classical model for aging studies, and has also proven useful for characterizing the response to high-glucose diets. However, studies on male animals are lacking. We found a surprising dichotomy: glucose regulates lifespan and aging in a sex specific manner, with beneficial effects on males compared to toxic effects on hermaphrodites. High-glucose diet resulted in greater mobility with age for males, along with a modest increase in median lifespan. In contrast, high-glucose diets decrease both lifespan and mobility for hermaphrodites. Understanding sex specific responses to high-glucose diets will be important for determining which evolutionarily conserved glucose-responsive pathways that regulate aging are "universal" and which are likely to be cell-type or sex-specific. PMID- 26143627 TI - Positioning Therapy for Ulcerative Colitis. AB - Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, characterized by diffuse mucosal inflammation, bloody diarrhea, and urgency. The mainstay of treatment has been mesalamine agents, steroids, thiopurines, and anti tumor necrosis factor alpha (TNF-alpha) antibodies. Over the past several years, new therapies have emerged which have provided clinicians new treatment options as well as new challenges in deciding which treatment is best for their patient at given points in their disease course. These agents include budesonide-Multi Matrix System (MMX), adalimumab, golimumab, and vedolizumab. In addition, randomized controlled trials have investigated a combination therapy of infliximab and azathioprine and a controlled trial of infliximab versus cyclosporine for intravenous steroid refractory UC. This review will focus on where these agents may be optimally positioned in treatment algorithms for UC. PMID- 26143628 TI - Sphincter of Oddi Dysfunction: Updates from the Recent Literature. AB - Sphincter of Oddi dysfunction (SOD) has long been a controversial topic, starting with whether it even exists, as a sphincterotomy-responsive entity to treat, for either: (1) post-cholecystectomy abdominal pain and/or (2) idiopathic recurrent acute pancreatitis (IRAP). Many of its aspects had required further research to better prove or refute its existence and to provide proper recommendations for physicians to diagnose and treat this condition. Fortunately, there has been major advancement in our knowledge in several areas over the past few years. New studies on challenging the classification, exploring alternative diagnostic methods, and quantifying the role of sphincterotomy in treatment of SOD for post cholecystectomy pain and for IRAP were recently published, including a randomized trial in each of the two areas. The goal of this paper is to review recent literature on selected important questions and to summarize the results of major trials in this field. PMID- 26143629 TI - Neuroenteric Staining as a Tool in the Evaluation of Pediatric Motility Disorders. AB - The diagnosis of enteric neuromuscular disorders has come a long way since the first description of an enteric neuropathic disorder by the Danish physician Harald Hirschsprung in 1886. Advances in specialized enteric histopathological staining techniques have made it possible to identify subtle neuropathies and myopathies that cause intestinal motility disorders, from the common and now better understood and relatively easily diagnosed Hirschsprung's disease to the less common and more severe and not well-characterized chronic idiopathic intestinal pseudoobstruction, which continues to present a diagnostic challenge to the gastroenterologist and histopathologist alike. This article will discuss the common gastrointestinal motility disorders and some of the specialized histological stains, such as the relatively common enzyme stain, acetylcholinesterase, used to diagnose Hirschsprung's disease; advanced tinctorial stains, such as Masson trichrome, which may aid in diagnosis of enteric myopathies causing pseudoobstruction; and immunohistochemical stains such as C-Kit or PG 9.5, which may aid in the diagnosis of enteric neuropathies causing pseudoobstruction. PMID- 26143630 TI - Sodium tanshinone IIA sulfonate ameliorates ischemia-induced myocardial inflammation and lipid accumulation in Beagle dogs through NLRP3 inflammasome. AB - BACKGROUND: The activation of NOD-like receptor (NLR) family, pyrin-domain containing 3 (NLRP3) inflammasome has now been proven to have a close connection with myocardial ischemia (MI) during acute phase, but the mechanisms are not completely clear. This study investigated the role of NLRP3 inflammasome in pathogenesis of MI injury including inflammation and lipid accumulation, as well as the effects of sodium tanshinone IIA sulfonate (STS) and diltiazem hydrochloride (DI). METHODS: Occlusion of left anterior descending (LAD) in canines was employed to induce MI. STS and DI were given intravenously 15 min after LAD occlusion. Cardiac function, inflammation and lipid levels, as well as related signaling pathways were determined. RESULTS: MI induced in Beagle dog was characterized by elevated ST-segment and increased CK-MB level in serum. Cardiac NLRP3 inflammasome was activated with elevated myocardial IL-1beta and IL-18 concentrations mediated by ROS over-production and TXNIP over-expression in MI dogs. Additionally, pro-inflammatory cytokines induced impairment of cardiac JAK2 STAT3 inflammatory pathway and insulin signaling pathway in this model, resulting in down-regulation of cardiac PPAR-alpha expression, subsequently causing lipid metabolism disorders characterized by elevation of myocardial lipid concentrations. These abnormalities were attenuated by the treatment of STS and DI. CONCLUSIONS: These data firstly demonstrated that cardiac NLRP3 inflammasome activation driven by cardiac ROS over-production and TXNIP up-expression resulted in impairment of the JAK2-STAT3 and insulin signaling pathways, leading to disorder of lipid metabolism in myocardial ischemic dogs through PPAR-alpha over expression. STS and DI might target cardiac NLRP3 inflammasome in preventing MI injury. PMID- 26143631 TI - A framework of boundary collision data aggregation into neighbourhoods. AB - A large portion of the total number of motor collisions can be boundary collisions; therefore, exaggerated or underestimated numbers for boundary collisions aggregated into neighbourhoods may hamper road safety analyses and management. In this paper, we propose a systematic framework for boundary collision aggregation. First, an entropy-based histogram thresholding method is utilized to determine the boundary zone size and identify boundary collisions. Next, the collision density probability distribution is then established, based on the collisions in each neighbourhood. Last, an effective boundary collision aggregation method, called the collision density ratio (CDR), is used to aggregate boundary collisions into neighbourhoods. The proposed framework is applied to collision data in the City of Edmonton for a case study. The experimental results show that the proposed entropy-based histogram thresholding method can identify boundary collision with the high precision and recall, and the proposed CDR method is more effective than the existing methods, the half-to half ratio method and the one-to-one ratio method, to aggregate boundary collisions into neighbourhoods. PMID- 26143632 TI - Induction of heme-oxygenase-1 (HO-1) does not enhance adiponectin production in human adipocytes: Evidence against a direct HO-1 - Adiponectin axis. AB - Adiponectin is a salutary adipokine and hypoadiponectinemia is implicated in the aetiology of obesity-related inflammation and cardiometabolic disease making therapeutic strategies to increase adiponectin attractive. Emerging evidence, predominantly from preclinical studies, suggests induction of heme-oxygenase-1 (HO-1) increases adiponectin production and reduces inflammatory tone. Here, we aimed to test whether induction of HO-1 enhanced adiponectin production from mature adipocytes. Treatment of human adipocytes with cobalt protoporphyrin (CoPP) or hemin for 24-48 h increased HO-1 expression and activity without affecting adiponectin expression and secretion. Treatment of adipocytes with TNFalpha reduced adiponectin secretion and increased expression and secretion of additional pro-inflammatory cytokines, IL-6 and MCP-1, as well as expression of sXBP-1, a marker of ER stress. HO-1 induction failed to reverse these effects. These results demonstrate that induction of HO-1 does not directly enhance adiponectin production or ameliorate the pro-inflammatory effects of TNFalpha and argue against a direct HO-1 - adiponectin axis. PMID- 26143633 TI - Obesity and late-onset hypogonadism. AB - Obesity and male hypogonadism (HG) are often associated, as demonstrated in all cross-sectional studies. Prospective studies have indicated that i) having HG at baseline increases the risk of visceral obesity (and metabolic syndrome) and that ii) obesity induces incident HG. Hence, there is a bidirectional relationship between the two conditions. This is the main topic of this review, along with some pathogenic considerations. Meta-analysis of intervention studies indicates that treating obesity is a very efficient treatment for obesity-induced HG. The mechanism by which obesity induces HG has not yet been completely understood, but dietary-induced hypothalamic inflammation, along with a decreased GnRH release, is plausible. Among patients seeking medical care for obesity, the proportion of HG is relatively high. The prevalence of obesity among patients referring for sexual dysfunction is also elevated. Hence, in symptomatic, obese, hypogonadal subjects, testosterone supplementation (TS) can be considered. Whereas long-term uncontrolled register studies suggest that TS could decrease weight, analysis of controlled studies only support a parallel increase in lean mass and decrease in fat mass, with a resulting null effect on weight. Considering that T induces an increase in muscle mass, it is conceivable that the amount of activity obese people can undertake after TS will increase, allowing a closer adherence to physical exercise programs. Some studies, here meta-analyzed, support this concept. PMID- 26143634 TI - The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer. AB - Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer. PMID- 26143635 TI - Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma: a comprehensive network meta-analysis of randomized controlled trials. AB - BACKGROUND: Several recent randomized clinical trials have preliminarily demonstrated that initial targeted therapy with combined BRAF and MEK inhibition is more effective in metastatic melanoma (MM) than single agent. To guide therapeutic decisions, we did a comprehensive network meta-analysis to identify evidence to robustly support whether combined BRAF and MEK inhibition is the best initial targeted therapeutic strategy for patients with MM. METHODS: The databases of PubMed and trial registries were researched for randomized clinical trials of targeted therapy. Data of outcome were extracted on progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Network meta-analysis using a Bayesian statistical model was performed to evaluate relative hazard ratio (HR) for PFS and OS, odds ratio (OR) for ORR. RESULTS: Finally, 16 eligible trials comprising 5976 participants were included in this meta-analysis. PFS were significantly prolonged in patients who received combined BRAF-MEK inhibition compared with those who received BRAF inhibition (HR: 0.58, 95%CI: 0.51-0.67, P < 0.0001) or MEK inhibition alone (HR: 0.29, 95%CI: 0.22 0.37, P < 0.0001). Combined BRAF-MEK inhibition also improved the OS over BRAF inhibition (HR: 0.67, 95%CI: 0.56-0.81, P < 0.0001) or MEK inhibition alone (HR: 0.48, 95%CI: 0.36-0.65, P < 0.0001). The ORR was superior in combined BRAF and MEK inhibition comparing with BRAF inhibition (OR: 2.00, 95%CI: 1.66-2.44, P < 0.0001) or MEK inhibition alone (OR: 20.66, 95%CI: 12.22-35.47, P < 0.0001). CONCLUSIONS: This study indicates that concurrent inhibition of BRAF and MEK improved the most effective therapeutic modality as compared as single BRAF or MEK inhibition for patients with MM. PMID- 26143636 TI - TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma. AB - Telomerase reverse transcriptase (TERT) activity is up-regulated in several types of tumors including glioblastoma (GBM). In the present study, 128 primary glioblastoma patients were examined for single nucleotide polymorphisms of TERT in blood and in 92 cases for TERT promoter mutations in tumors. TERT promoter mutations were observed in 86% of the tumors and of these, C228T (-124 bp upstream start codon) was detected in 75% and C250T (-146 bp) in 25% of cases. TERT promoter mutations were associated with shorter overall survival (11 vs. 20 months p = 0.002 and 12 vs. 20, p = 0.04 for C228T and C250T, respectively). The minor alleles of rs2736100 and rs10069690 SNP's, located in intron 2 and the promotor regions, respectively, were associated with an increased risk of developing GBM (p = 0.004 and 0.001). GBM patients having both TERT promoter mutations and being homozygous carriers of the rs2853669 C-allele displayed significantly shorter overall survival than those with the wild type allele. The rs2853669 SNP is located in a putative Ets2 binding site in the promoter (-246 bp upstream start codon) close to the C228T and C250T mutation hot spots. Interleukin-6 (IL-6) expression regulated by TERT promoter status and polymorphism, what leads us to think that TERT and IL-6 plays a significant role in GBM, where specific SNPs increase the risk of developing GBM while the rs2853669 SNP and specific mutations in the TERT promoter of the tumor lead to shorter survival. PMID- 26143637 TI - pHLIP-mediated targeting of truncated tissue factor to tumor vessels causes vascular occlusion and impairs tumor growth. AB - Occluding tumor blood supply by delivering the extracellular domain of coagulation-inducing protein tissue factor (truncated tissue factor, tTF) to tumor vasculature has enormous potential to eliminate solid tumors. Yet few of the delivery technologies are moved into clinical practice due to their non specific tissue biodistribution and rapid clearance by the reticuloendothelial system. Here we introduced a novel tTF delivery method by generating a fusion protein (tTF-pHLIP) consisting of tTF fused with a peptide with a low pH-induced transmembrane structure (pHLIP). This protein targets the acidic tumor vascular endothelium and effectively induces local blood coagulation. tTF-pHLIP, wherein pHLIP is cleverly designed to mimic the natural tissue factor transmembrane domain, triggered thrombogenic activity of the tTF by locating it to the endothelial cell surface, as demonstrated by coagulation assays and confocal microscopy. Systemic administration of tTF-pHLIP into tumor-bearing mice selectively induced thrombotic occlusion of tumor vessels, reducing tumor perfusion and impairing tumor growth without overt side effects. Our work introduces a promising strategy for using tTF as an anti-cancer drug, which has great potential value for clinical applications. PMID- 26143638 TI - Vascular endothelial growth factor expression correlates with serum CA125 and represents a useful tool in prediction of refractoriness to platinum-based chemotherapy and ascites formation in epithelial ovarian cancer. AB - There is an increasing need for the identification of novel biological markers and potential therapeutic targets in epithelial ovarian cancer (EOC). Given the critical role of growth factors in the biology of EOC, we aimed in the present study to evaluate the intratumoral expressions of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) proteins and their clinical relevance in a cohort of 100 patients with EOC. All patients received platinum based chemotherapy after surgery. A comparative immunohistochemical study of normal ovarian and EOC tissues showed that both growth factors were expressed at higher levels in tumor samples. In our statistical analysis, while no association existed between the FGF expression status and the clinicopathological characteristics of patients, intratumoral VEGF was identified as a potential biomarker for the prediction of ascites formation. In addition, the expression status of VEGF appeared to independently predict overall survival and response to chemotherapy. Furthermore, a direct association was demonstrated between the pre treatment VEGF expression and serum CA125 after three cycles of chemotherapy. In sum, we report for the first time to our knowledge the correlation between intratumoral VEGF and serum CA125 in EOC. Our data also shows the prognostic value of VEGF expression in EOC. These results suggest the potential value of intratumoral VEGF in patient stratification. Dual inhibition of VEGF and CA125 might bring about a better outcome for patients with EOC. PMID- 26143639 TI - Brain development is impaired in c-fos -/- mice. AB - c-Fos is a proto-oncogene involved in diverse cellular functions. Its deregulation has been associated to abnormal development and oncogenic progression. c-fos-/- mice are viable but present a reduction in their body weight and brain size. We examined the importance of c-Fos during neocortex development at 13.5, 14.5 and 16.5 days of gestation. At E14.5, neocortex thickness, apoptosis, mitosis and expression of markers along the different stages of Neural Stem Progenitor Cells (NSPCs) differentiation in c-fos-/- and wild-type mice were analyzed. A ~15% reduction in the neocortex thickness of c fos-/- embryos was observed which correlates with a decrease in the number of differentiated cells and an increase in apoptosis at the ventricular zone. No difference in mitosis rate was observed, although the mitotic angle was predominantly vertical in c-fos-/- embryos, suggesting a reduced trend of NSPCs to differentiate. At E13.5, changes in differentiation markers start to be apparent and are still clearly observed at E16.5. A tendency of more AP-1/DNA complexes present in nuclear extracts of cerebral cortex from c-fos-/- embryos with no differences in the lipid synthesis activity was found. These results suggest that c-Fos is involved in the normal development of NSPCs by means of its AP-1 activity. PMID- 26143640 TI - Intron-based genomic editing: a highly efficient method for generating knockin zebrafish. AB - The TALEN and CRISPR/Cas9 nuclease systems have been extensively utilized in genomic engineering of model organisms. In zebrafish, the nuclease systems have been successfully applied in generating loss-of-function knockout lines. However, genome-specific knockin techniques in zebrafish are still at the beginning. In this perspective, we briefly summarize the recent progresses on knockin approaches in zebrafish with a special focus on the newly developed intron-based knockin method. PMID- 26143642 TI - Derivation and validation of an HbA1c optimal cutoff for diagnosing prediabetes in a South African mixed ancestry population. AB - INTRODUCTION: Prediabetes compromises impaired fasting glucose and impaired glucose tolerance and is a high risk for future diabetes mellitus and cardiovascular disease. Traditional diagnostic methods involve a fasting sample or oral glucose tolerance test, which is cumbersome, time-consuming and inconvenient. An HbA1c-based approach has been incorporated into new guidelines, but cut-offs may vary and have not been defined for all population groups. We derived and validated HbA1c cut-offs to diagnose prediabetes in mixed ancestry South Africans. METHODS: Participants were 667 (derivation sample), 234 (validation sample 1) and 674 (validation sample 2) diabetes-free individuals. They underwent standard 2-hour OGTT with HbA1c test. Receiver-operator characteristic curves were used to determine optimal HbA1c cut-off to predict prediabetes. RESULTS: A total of 27.7% participants in the derivation sample had prediabetes versus 17.5% (validation sample 1) and 15.4% (validation sample 2). The optimal cut-off was 5.75% in all three cohorts with sensitivity and specificity of 64.8% and 60.4% in combined derivation and validation sample 1, and 59.6% and 69.8% in validation sample 2. CONCLUSION: The discriminatory capacity of HbA1c for predicting prediabetes in this population is modest at the derived cut-off. The use of HbA1c alone in this setting may result in an inaccurate diagnosis. PMID- 26143641 TI - Time-course gene profiling and networks in demethylated retinoblastoma cell line. AB - Retinoblastoma, a very aggressive cancer of the developing retina, initiatiates by the biallelic loss of RB1 gene, and progresses very quickly following RB1 inactivation. While its genome is stable, multiple pathways are deregulated, also epigenetically. After reviewing the main findings in relation with recently validated markers, we propose an integrative bioinformatics approach to include in the previous group new markers obtained from the analysis of a single cell line subject to epigenetic treatment. In particular, differentially expressed genes are identified from time course microarray experiments on the WERI-RB1 cell line treated with 5-Aza-2'-deoxycytidine (decitabine; DAC). By inducing demethylation of CpG island in promoter genes that are involved in biological processes, for instance apoptosis, we performed the following main integrative analysis steps: i) Gene expression profiling at 48h, 72h and 96h after DAC treatment; ii) Time differential gene co-expression networks and iii) Context driven marker association (transcriptional factor regulated protein networks, master regulatory paths). The observed DAC-driven temporal profiles and regulatory connectivity patterns are obtained by the application of computational tools, with support from curated literature. It is worth emphasizing the capacity of networks to reconcile multi-type evidences, thus generating testable hypotheses made available by systems scale predictive inference power. Despite our small experimental setting, we propose through such integrations valuable impacts of epigenetic treatment in terms of gene expression measurements, and then validate evidenced apoptotic effects. PMID- 26143643 TI - Response from Dr. Roucka. PMID- 26143645 TI - Bacteremia in children: epidemiology, clinical diagnosis and antibiotic treatment. AB - The diagnosis of bacteremia in children is important and it can be clinically challenging to recognize the signs and symptoms. The reported rates of bacteremia are higher in young children but with the increasing vaccine coverage, there has been a decrease in bacteremia due to the three vaccine preventable bacteria (Streptococcus pneumoniae, Haemophilus influenzae group b and Neisseria meningitidis). Notably, there have been increases in healthcare-associated bacteremias with a rise in Staphylococcus aureus and Gram negative bacteremias. This review provides a brief overview of the clinical diagnosis of bacteremia in children, focusing on the epidemiology, clinical characteristics, risk factors, antibiotic treatment, outcomes and preventative measures to reduce the incidence of bacteremia and improve morbidity and mortality. PMID- 26143644 TI - Quantitative Differences in the Urinary Proteome of Siblings Discordant for Type 1 Diabetes Include Lysosomal Enzymes. AB - Individuals with type 1 diabetes (T1D) often have higher than normal blood glucose levels, causing advanced glycation end product formation and inflammation and increasing the risk of vascular complications years or decades later. To examine the urinary proteome in juveniles with T1D for signatures indicative of inflammatory consequences of hyperglycemia, we profiled the proteome of 40 T1D patients with an average of 6.3 years after disease onset and normal or elevated HbA1C levels, in comparison with a cohort of 41 healthy siblings. Using shotgun proteomics, 1036 proteins were identified, on average, per experiment, and 50 proteins showed significant abundance differences using a Wilcoxon signed-rank test (FDR q-value <= 0.05). Thirteen lysosomal proteins were increased in abundance in the T1D versus control cohort. Fifteen proteins with functional roles in vascular permeability and adhesion were quantitatively changed, including CD166 antigen and angiotensin-converting enzyme 2. alpha-N-Acetyl galactosaminidase and alpha-fucosidase 2, two differentially abundant lysosomal enzymes, were detected in western blots with often elevated quantities in the T1D versus control cohort. Increased release of proteins derived from lysosomes and vascular epithelium into urine may result from hyperglycemia-associated inflammation in the kidney vasculature. PMID- 26143646 TI - Healthy Lifestyle Interventions to Combat Noncommunicable Disease-A Novel Nonhierarchical Connectivity Model for Key Stakeholders: A Policy Statement From the American Heart Association, European Society of Cardiology, European Association for Cardiovascular Prevention and Rehabilitation, and American College of Preventive Medicine. AB - Noncommunicable diseases (NCDs) have become the primary health concern for most countries around the world. Currently, more than 36 million people worldwide die from NCDs each year, accounting for 63% of annual global deaths; most are preventable. The global financial burden of NCDs is staggering, with an estimated 2010 global cost of $6.3 trillion (US dollars) that is projected to increase to $13 trillion by 2030. A number of NCDs share one or more common predisposing risk factors, all related to lifestyle to some degree: (1) cigarette smoking, (2) hypertension, (3) hyperglycemia, (4) dyslipidemia, (5) obesity, (6) physical inactivity, and (7) poor nutrition. In large part, prevention, control, or even reversal of the aforementioned modifiable risk factors are realized through leading a healthy lifestyle (HL). The challenge is how to initiate the global change, not toward increasing documentation of the scope of the problem but toward true action-creating, implementing, and sustaining HL initiatives that will result in positive, measurable changes in the previously defined poor health metrics. To achieve this task, a paradigm shift in how we approach NCD prevention and treatment is required. The goal of this American Heart Association/European Society of Cardiology/European Association for Cardiovascular Prevention and Rehabilitation/American College of Preventive Medicine policy statement is to define key stakeholders and highlight their connectivity with respect to HL initiatives. This policy encourages integrated action by all stakeholders to create the needed paradigm shift and achieve broad adoption of HL behaviors on a global scale. PMID- 26143648 TI - A case-control study of risk factors for rotavirus infections in adults, Denmark, 2005-2009. AB - Rotavirus (RV) infections affect young children, but can also occur in adults. We sought to identify risk factors for RV infections in adults aged ?18 years in Denmark, and to describe illness and genotyping characteristics. From March 2005 to February 2009, we recruited consecutive cases of laboratory-confirmed RV infection and compared them with healthy controls matched by age, gender and municipality of residence. We collected information on illness characteristics and exposures using postal questionnaires. We calculated univariable and multivariable matched odds ratios (mOR) with conditional logistic regression. The study comprised 65 cases and 246 controls. Illness exceeded 10 days in 31% of cases; 22% were hospitalized. Cases were more likely than controls to suffer serious underlying health conditions [mOR 5.6, 95% confidence interval (CI) 1.7 18], and to report having had close contact with persons with gastrointestinal symptoms (mOR 9.4, 95% CI 3.6-24), in particular young children aged 18 years. Close contact with young children or adults with gastrointestinal symptoms is the main risk factor for RV infection in adults in Denmark. RV vaccination assessments should consider that RV vaccination in children may indirectly reduce the burden of disease in adults. PMID- 26143649 TI - Validation of the comprehensive diagnostic criteria for IgG4-related disease in a SMART registry. PMID- 26143647 TI - Pharmacokinetic modeling of therapies for systemic lupus erythematosus. AB - With the increasing use of different types of therapies in treating autoimmune diseases such as systemic lupus erythematosus (SLE), there is a need to utilize pharmacokinetic (PK) strategies to optimize the clinical outcome of these treatments. Various PK analysis approaches, including population PK modeling and physiologically based PK modeling, have been used to evaluate drug PK characteristics and population variability or to predict drug PK profiles in a mechanistic manner. This review outlines the PK modeling of major SLE therapies including immunosuppressants (methotrexate, azathioprine, mycophenolate and cyclophosphamide, among others) and immunomodulators (intravenous immunoglobulin). It summarizes the population PK modeling, physiologically based PK modeling and model-based individualized dosing strategies to improve the therapeutic outcomes in SLE patients. PMID- 26143650 TI - Comparison of surgical treatments for triple extensor tendon ruptures in rheumatoid hands: A retrospective study of 48 cases. AB - OBJECTIVE: This retrospective study was designed to evaluate the outcomes of four different surgical reconstructions for extensor tendon ruptures in ulnar three fingers in 48 patients with rheumatoid arthritis. METHODS: The following four techniques were performed; palmaris longus tendon grafting (PL group; n = 9), extensor indicis proprius (EIP) tendon transfers (EIP group; n = 8), end-to-side transfers with tension-reduced early mobilization (End-to-side group; n = 16), and a combination of end-to-side and EIP transfers (Combination group; n = 15). Loss of extension was evaluated to determine the mean postoperative range of motion of the metacarpophalangeal (MP) joint and clinical outcomes were categorized using modified Geldmacher criteria. RESULTS: Combination group demonstrated the best mean MP joint extension (-3 degrees ), followed by End-to side group (-12 degrees ), EIP group (-16 degrees ), and PL group (-21 degrees ). Combination group yielded the best clinical outcomes with all cases showing good results. CONCLUSIONS: The combination of end-to-side and EIP transfer was an effective surgical reconstruction procedure for triple fingers extension loss. PMID- 26143651 TI - Influence of pasture-based feeding systems on fatty acids, organic acids and volatile organic flavour compounds in yoghurt. AB - The influence of different pasture-based feeding systems on fatty acids, organic acids and volatile organic flavour compounds in yoghurt was studied. Pasture is the main source of nutrients for dairy cows in many parts of the world, including southeast Australia. Milk and milk products produced in these systems are known to contain a number of compounds with positive effects on human health. In the current study, 260 cows were fed supplementary grain and forage according to one of 3 different systems; Control (a traditional pasture based diet offered to the cows during milking and in paddock), PMR1 (a partial mixed ration which contained the same supplement as Control but was offered to the cows as a partial mixed ration on a feedpad), PMR 2 (a differently formulated partial mixed ration compared to Control and PMR1 which was offered to the cows on a feedpad). Most of the yoghurt fatty acids were influenced by feeding systems; however, those effects were minor on organic acids. The differences in feeding systems did not lead to the formation of different volatile organic flavour compounds in yoghurt. Yet, it did influence the relative abundance of these components. PMID- 26143652 TI - Outcoupling-Enhanced Flexible Organic Light-Emitting Diodes on Ameliorated Plastic Substrate with Built-in Indium-Tin-Oxide-Free Transparent Electrode. AB - Enhancing light outcoupling in flexible organic light-emitting diodes (FOLEDs) is an important task for increasing their efficiencies for display and lighting applications. Here, a strategy for an angularly and spectrally independent boost in light outcoupling of FOLEDs is demonstrated by using plastic substrates with a low refractive index, consisting of a bioinspired optical coupling layer and a transparent conductive electrode composed of a silver network. The good transmittance to full-color emission (>94% over the whole visible wavelength range), ultralow sheet resistance to carrier injection (<5 Omega sq(-1)), and high tolerance to mechanical bending of the ameliorated plastic substrates synergistically optimize the device performance of FOLEDs. The maximum power efficiencies reach 47, 93, 56, and 52 lm W(-1) for red, green, blue, and white emissions, which are competitive with similarly structured OLEDs fabricated on traditional indium-tin-oxide (ITO) glass. This paradigm for light outcoupling enhancement in ITO-free FOLEDs offers additional features and design freedoms for highly efficient flexible optoelectronics in large-scale and low-cost manufacturing without the need for a high-refractive-index plastic substrate. PMID- 26143653 TI - Autologous fat augmentation of the vocal fold with basic fibroblast growth factor: Computed tomographic assessment of fat tissue survival after augmentation. AB - CONCLUSION: The volume of fat tissue loss after vocal fold augmentation can be decreased when augmentation is performed with addition of basic fibroblast growth factor (b-FGF). OBJECTIVES: The effectiveness of augmentation is easily decreased due to absorption. Canine experiments have confirmed that the decreased effectiveness caused by absorption after augmentation can be reduced by administering low-concentration b-FGF. Clinical application was trialed after acquiring approval from the institutional clinical review committee. METHOD: Autologous fat tissue with b-FGF was injected into the vocal folds in cases of unilateral vocal cord paralysis. This study compared fat tissue survival after injection by assessing images from computed tomography (CT). RESULTS: Assessments using CT revealed that the decrease in volume of injected fat tissue was smaller in cases treated using b-FGF than in cases using the conventional method. No severe complications were encountered using this method. PMID- 26143654 TI - Effect of stallion age on the expression of LH and FSH receptors and aromatase P450 in equine male reproductive tissues. AB - The aim of the present study was to characterise receptors for LH and FSH (LHR and FSHR, respectively) and aromatase in epididymal and testicular tissue from stallions of different ages (prepubertal, young, mature and old). Gene and protein expression were assessed by real-time quantitative polymerase chain reaction (real-time qPCR), immunohistochemistry and multiple immunofluorescence labelling. There were no differences in LHR mRNA expression in epididymal and testicular parenchyma in stallions of different age. In contrast, expression of FSHR and CYP19A1 in caput, corpus and cauda epididymis and in testicular parenchyma increased with age (P<0.001). Immunolabelling for LHR, FSHR and aromatase was influenced by puberty. In postpubertal stallions, positive staining for LHR and aromatase was detected in Leydig cells, whereas protein expression of FSHR was present in Sertoli cells and primary spermatocytes. In prepubertal colts, staining for LHR, FSHR and aromatase was detected in seminiferous tubules. In epididymal tissue, aromatase was present in the cauda epididymis only, regardless of age. In conclusion, the results highlight the significance of gonadotropin action and oestrogen production for the maturation of male reproductive tissue in the horse. The presence of FSHR in the seminiferous tubules suggests effects of FSH on spermatogenesis in this species. The importance of oestrogen production for maintenance of testicular function in stallions was confirmed. PMID- 26143656 TI - MDN: A Web Portal for Network Analysis of Molecular Dynamics Simulations. AB - We introduce a web portal that employs network theory for the analysis of trajectories from molecular dynamics simulations. Users can create protein energy networks following methodology previously introduced by our group, and can identify residues that are important for signal propagation, as well as measure the efficiency of signal propagation by calculating the network coupling. This tool, called MDN, was used to characterize signal propagation in Escherichia coli heat-shock protein 70-kDa. Two variants of this protein experimentally shown to be allosterically active exhibit higher network coupling relative to that of two inactive variants. In addition, calculations of partial coupling suggest that this quantity could be used as part of the criteria to determine pocket druggability in drug discovery studies. PMID- 26143655 TI - Structure-Encoded Global Motions and Their Role in Mediating Protein-Substrate Interactions. AB - Recent structure-based computational studies suggest that, in contrast to the classical description of equilibrium fluctuations as wigglings and jigglings, proteins have access to well-defined spectra of collective motions, called intrinsic dynamics, encoded by their structure under native state conditions. In particular, the global modes of motions (at the low frequency end of the spectrum) are shown by multiple studies to be highly robust to minor differences in the structure or to detailed interactions at the atomic level. These modes, encoded by the overall fold, usually define the mechanisms of interactions with substrates. They can be estimated by low-resolution models such as the elastic network models (ENMs) exclusively based on interresidue contact topology. The ability of ENMs to efficiently assess the global motions intrinsically favored by the overall fold as well as the relevance of these predictions to the dominant changes in structure experimentally observed for a given protein in the presence of different substrates suggest that the intrinsic dynamics plays a role in mediating protein-substrate interactions. These observations underscore the functional significance of structure-encoded dynamics, or the importance of the predisposition to favor functional global modes in the evolutionary selection of structures. PMID- 26143657 TI - Diagnostic arthroscopy in the treatment of minimally displaced lateral humeral condyle fractures in children. AB - INTRODUCTION: In minimally displaced pediatric lateral humeral condyle fractures, plain radiography cannot be used for accurate differential diagnosis of the cartilage lesion, and other imaging methods have demerits in their accuracy and their accessibility. The purpose of this study was to investigate the usefulness of arthroscopy to diagnose cartilage displacement in minimally displaced fractures. MATERIALS AND METHODS: Nine children with minimally displaced lateral humeral condyle fractures, an average of 6.6 years old, underwent combined arthroscopy and fixation surgery. Percutaneous fixation was performed with nondisplaced articular surface according to the arthroscopic findings, while in case of displaced fracture under arthroscopy, open fixation was preferred. The difference between the arthroscopic and radiographic findings was investigated. RESULTS: Articular surface could be arthroscopically visualized in all patients. Under arthroscopy, cartilage hinges were maintained in seven cases and disrupted in two. Nondisplaced cartilage disruption was noted in one of these two cases, and percutaneous fixation was performed. A displaced articular surface was noted in the other one, where the patient underwent open surgery. At the last follow up, an average of 14.7 months postoperatively, union and wide range of motion had been achieved without any complications. CONCLUSION: Diagnosis of fracture displacement by merely using plain radiography was considered to be insufficient for minimally displaced cases. Diagnostic arthroscopy aided in the appropriate selection of either a percutaneous or open fixation method. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26143658 TI - Comparative Study of Graphite-Supported LDI- and ESI-FT-ICR-MS of a Pyrolysis Liquid from a German Brown Coal. AB - Pyrolysis liquids from coal are complex mixtures of organic compounds with low to high molecular mass and low to high polarity. Compared to low-molecular-weight compounds, little information is available regarding high-molecular-weight compounds in pyrolysis liquids, although their characterization is important for the elucidation of degradation pathways. In this study, laser desorption ionization (LDI) using graphite powder as the support material has been used in conjunction with Fourier transform ion cyclotron resonance mass spectrometry (FT ICR-MS) for the analysis of a pyrolysis liquid from brown coal. The acquired data is compared to previous results of the same sample using electrospray ionization (ESI). Using LDI, compounds with masses between 300 and 900 Da were detected by LDI. An evaluation of the spectra was based on the frequency of molecular formulas with a different number of heteroatoms. Hydrocarbon compounds and heteroatomic compounds containing oxygen and sulfur were found. A comparison to ESI results shows that the numbers of observed molecular formulas are virtually the same, but a higher quantity of molecular formulas with a low number of oxygen can be detected by LDI. The observation of molecular formulas without oxygen is a unique feature of the LDI spectra. A more detailed investigation was possible by the utilization of double bond equivalent plots versus carbon number, which revealed a prevalence of LDI for the ionization of compounds with higher DBE. PMID- 26143659 TI - Ethyl 2-((4-Chlorophenyl)amino)thiazole-4-carboxylate and Derivatives Are Potent Inducers of Oct3/4. AB - The octamer-binding transcription factor 4 (Oct3/4) is a master gene in the transcriptional regulatory network of pluripotent cells. Repression of Oct3/4 in embryonic stem cells (ESCs) is associated with cell differentiation and loss of pluripotency, whereas forced overexpression in cooperation with other transcriptional factors, such as Nanog, Sox2, and Lin28, can reprogram somatic cells back into pluripotent cells, termed induced pluripotent stem cells (iPSCs). However, random integration and potential tumorigenic transformation caused by viral transduction limit the clinical application of iPSCs. By performing a cell based high throughput screening (HTS) campaign, we identified several potential small molecules as inducers of Oct3/4 expression. Here we report a lead structure ethyl 2-((4-chlorophenyl)amino)-thiazole-4-carboxylate, termed O4I2, showing high activity in enforcing Oct3/4 expression. On the basis of chemical expansion, we further identified derivatives having increased activities toward Oct3/4 induction. Thus, O4I2 and its derivatives should provide a new class of small molecules suitable for iPSC generation. PMID- 26143661 TI - High-mobility group box 1 is involved in the development of benign prostatic hyperplasia with chronic prostatic inflammation. AB - OBJECTIVE: The aims of this study were to explore the role of high-mobility group box 1 (HMGB1) in benign prostatic hyperplasia (BPH) and to perform a preliminary investigation of the mechanisms underlying BPH. MATERIALS AND METHODS: HMGB1 expression in 160 BPH cases was analyzed using immunohistochemistry. HMGB1 expression in primary prostate epithelial cells and the concentration of HMGB1 in the surrounding culture medium were detected by Western blotting and enzyme linked immunosorbent assay, respectively. Cell proliferation was evaluated by the carboxyfluorescein succinimidyl ester (CFSE) dilution assay. Student's t test or a one- or two-way analysis of variance test, followed by Bonferroni post hoc analysis, were used to test differences between groups and time-course data. RESULTS: HMGB1 expression was higher in BPH with prostatitis than in BPH alone and was positively correlated with prostate volume in BPH patients with prostatitis, but not in BPH patients without prostatitis. HMGB1 expression in primary prostate epithelial cells as well as its release into the extracellular environment increased when the cells were treated with the proinflammatory molecule lipopolysaccharide (LPS). In addition, HMGB1 overexpression promoted the proliferation of primary prostate epithelial cells under LPS stimulation, and this could be inhibited by the HMGB1 antagonist boxA. CONCLUSIONS: These findings provide novel insights into the pathogenic role of HMGB1 in BPH with prostatitis, and suggest that HMGB1 is a potential biomarker and therapeutic target for BPH. PMID- 26143660 TI - Cell-Type-Specific Activity in Prefrontal Cortex during Goal-Directed Behavior. AB - The prefrontal cortex (PFC) plays a key role in controlling goal-directed behavior. Although a variety of task-related signals have been observed in the PFC, whether they are differentially encoded by various cell types remains unclear. Here we performed cellular-resolution microendoscopic Ca(2+) imaging from genetically defined cell types in the dorsomedial PFC of mice performing a PFC-dependent sensory discrimination task. We found that inhibitory interneurons of the same subtype were similar to each other, but different subtypes preferentially signaled different task-related events: somatostatin-positive neurons primarily signaled motor action (licking), vasoactive intestinal peptide positive neurons responded strongly to action outcomes, whereas parvalbumin positive neurons were less selective, responding to sensory cues, motor action, and trial outcomes. Compared to each interneuron subtype, pyramidal neurons showed much greater functional heterogeneity, and their responses varied across cortical layers. Such cell-type and laminar differences in neuronal functional properties may be crucial for local computation within the PFC microcircuit. PMID- 26143662 TI - Predictors of surgical site infection after hospital discharge in patients undergoing major vascular surgery. AB - OBJECTIVE: Surgical site infection (SSI) is one of the most common postoperative complications after vascular reconstruction, producing significant morbidity and hospital readmission. In contrast to SSI that develops while patients are still hospitalized, little is known about the cohort of patients who develop SSI after discharge. In this study, we explore the factors that lead to postdischarge SSI, investigate the differences between risk factors for in-hospital vs postdischarge SSI, and develop a scoring system to identify patients who might benefit from postdischarge monitoring of their wounds. METHODS: Patients who underwent major vascular surgery from 2005 to 2012 for aneurysm and lower extremity occlusive disease were identified from the American College of Surgeons National Surgical Quality Improvement Program Participant Use Files. Patients were categorized as having no SSI, in-hospital SSI, or SSI after hospital discharge. Predictors of postdischarge SSI were determined by multivariable logistic regression and internally validated by bootstrap resampling. Risk scores were assigned to all significant variables in the model. Summative risk scores were collapsed into quartile-based ordinal categories and defined as low, low/moderate, moderate/high, and high risk. Multivariable logistic regression was used to determine predictors of in-hospital SSI. RESULTS: Of the 49,817 patients who underwent major vascular surgery, 4449 (8.9%) were diagnosed with SSI (2.1% in hospital SSI; 6.9% postdischarge SSI). By multivariable analysis, factors significantly associated with increased odds of postdischarge SSI include female gender, obesity, diabetes, smoking, hypertension, coronary artery disease, critical limb ischemia, chronic obstructive pulmonary disease, dyspnea, neurologic disease, prolonged operative time >4 hours, American Society of Anesthesiology class 4 or 5, lower extremity revascularization or aortoiliac procedure, and groin anastomosis. The model exhibited moderate discrimination (bias-corrected C statistic, 0.691) and excellent internal calibration. The postdischarge SSI rate was 2.1% for low-risk patients, 5.1% for low/moderate-risk patients, 7.8% for moderate/high-risk patients, and 14% for high-risk patients. In a comparative analysis, comorbidities were the primary driver of postdischarge SSI, whereas in-hospital factors (operative time, emergency case status) and complications predicted in-hospital SSI. CONCLUSIONS: The majority of SSIs after major vascular surgery develop following hospital discharge. We have created a scoring system that can select a cohort of patients at high risk for SSI after discharge. These patients can be targeted for transitional care efforts focused on early detection and treatment with the goal of reducing morbidity and preventing readmission secondary to SSI. PMID- 26143664 TI - Effects of donepezil and serotonin reuptake inhibitor on acute regression during adolescence in Down syndrome. AB - A 14-year-old boy with Down syndrome (DS) showed a gradual decline in his daily activities and feeding capacities, and a marked deterioration triggered by a streptococcal infection was observed at the age of 15 years. He became bedridden, accompanied by sleep disturbance, sustained upward gaze, and generalized rigidity. Magnetic resonance imaging showed unremarkable findings, but antiglutamate receptor autoantibodies were positive in his cerebrospinal fluid. Treatment with thiamine infusion and steroid pulse therapy showed little effect, but gross motor dysfunction and appetite loss were ameliorated by the administration of l-DOPA and serotonin reuptake inhibitors. Thereafter, autistic behaviors predominated, including loss of social interaction, oral tendency, water phobia, and aggressiveness. Initiation of donepezil, an acetylcholinesterase inhibitor, resulted in the disappearance of these symptoms and total recovery of the patient to his previous psychosocial levels. We hypothesize that the acute regression in adolescence represents a process closely related to the defects of serotonergic and cholinergic systems that are innate to DS brains and not just a nonspecific comorbidity of depression or limbic encephalitis. PMID- 26143665 TI - Apples, oranges, and statistical magic: Limitations of registry studies and need for collaborative studies. PMID- 26143679 TI - The Contact Zone: A Common Site of Tumor Recurrence in a Patient Who Underwent Skin-Sparing Mastectomy and Myocutaneous Flap Reconstruction. AB - Routine magnetic resonance imaging (MRI) screening is not typically warranted in asymptomatic patients with a history of breast cancer and myocutaneous flap reconstruction due to the rare incidence of local tumor recurrence. We present a case of recurrent invasive ductal carcinoma along the contact zone between the transverse rectus abdominis myocutaneous (TRAM) flap and the native breast tissue that was incidentally detected on a routine high-risk screening-MRI of the breast in an asymptomatic patient with a history of breast cancer. PMID- 26143680 TI - Comments about the status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. PMID- 26143681 TI - Anaphylaxis. Beyond the skin. PMID- 26143682 TI - Expression of somatostatin, dopamine, progesterone and growth hormone receptor mRNA in canine cortisol-secreting adrenocortical tumours. AB - Cortisol-secreting adrenocortical tumours (AT) in dogs are characterised by uncontrolled growth and excessive cortisol secretion. Dysregulated hormone receptor expression might be involved in tumour growth and hypersecretion of cortisol. The relative mRNA expression of growth hormone receptor, progesterone receptor, somatostatin receptors (SSTR1-3) and dopamine receptors (DRD1-2 and DRD5) was evaluated in 36 canine ATs and 15 adrenal glands obtained from healthy dogs. Compared with normal adrenal tissue, DRD2 mRNA expression was relatively lower in carcinomas, while SSTR1 mRNA expression was lower in both adenomas and carcinomas. Both of these features might contribute to loss of inhibition of tumour growth and upregulation of cortisol secretion. In canine ATs that had recurred within 30 months of surgical adrenalectomy, a marked increase in expression of DRD1 mRNA was observed. Targeting of specific hormone receptors, expressed by ATs, might be exploited for therapy. PMID- 26143683 TI - Red and processed meat consumption and mortality: dose-response meta-analysis of prospective cohort studies. AB - OBJECTIVE: To examine and quantify the potential dose-response relationship between red and processed meat consumption and risk of all-cause, cardiovascular and cancer mortality. DESIGN: We searched MEDLINE, Embase, ISI Web of Knowledge, CINHAL, Scopus, the Cochrane library and reference lists of retrieved articles up to 30 November 2014 without language restrictions. We retrieved prospective cohort studies that reported risk estimates for all-cause, cardiovascular and cancer mortality by red and/or processed meat intake levels. The dose-response relationships were estimated using data from red and processed meat intake categories in each study. Random-effects models were used to calculate pooled relative risks and 95 % confidence intervals and to incorporate between-study variations. RESULTS: Nine articles with seventeen prospective cohorts were eligible in this meta-analysis, including a total of 150 328 deaths. There was evidence of a non-linear association between processed meat consumption and risk of all-cause and cardiovascular mortality, but not for cancer mortality. For processed meat, the pooled relative risk with an increase of one serving per day was 1.15 (95 % CI 1.11, 1.19) for all-cause mortality (five studies; P<0.001 for linear trend), 1.15 (95 % CI 1.07, 1.24) for cardiovascular mortality (six studies; P<0.001) and 1.08 (95 % CI 1.06, 1.11) for cancer mortality (five studies; P<0.001). Similar associations were found with total meat intake. The association between unprocessed red meat consumption and mortality risk was found in the US populations, but not in European or Asian populations. CONCLUSIONS: The present meta-analysis indicates that higher consumption of total red meat and processed meat is associated with an increased risk of total, cardiovascular and cancer mortality. PMID- 26143684 TI - Theileria orientalis: a review. AB - Theileria orientalis (also known historically as T. sergenti and T. buffeli) is responsible for benign or non-transforming theileriosis, and exerts its major effect through erythrocyte destruction. The life cycle of T. orientalis is essentially similar to that of other Theileria species, except that the schizonts do not induce transformation and fatal lymphoproliferation. The pathogenesis of anaemia as a result of infection is not clearly established and may be multifaceted. Clinical signs of weakness, reluctance to walk and abortion are early but non-specific indications of disease, particularly if accompanied by a history of cattle being moved. Physical examination may reveal pallor (pale eyes, vaginal mucosa), pyrexia, and elevated heart and respiratory rates. T. orientalis is an economically important parasite of cattle in New Zealand, Australia and Japan, especially where naive animals are introduced into an endemic area or in animals under stress. Increased awareness of the risks posed by the parasite is required to enable management practices to be implemented to minimise its impact. PMID- 26143685 TI - Risk factors associated with postoperative delirium after surgery for oral cancer. AB - OBJECTIVE: The purpose of this study was to retrospectively investigate the multivariate relationships among the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. MATERIAL AND METHODS: The medical records of all patients with oral cancer who underwent curative head and neck surgery between April 2011 and March 2013 at our institution were retrospectively reviewed. There was a total of 188 patients, including 110 males and 78 females. RESULTS: We found that older age, extensive surgical procedure, longer operation, excessive hemorrhage, blood transfusion, longer postoperative management in the intensive care unit, longer postoperative hospital stay, lower albumin level in the preoperative blood test, and lower total protein, albumi, n and hemoglobin levels and a higher C-reactive protein (CRP) level in the postoperative blood tests were significant variables in the univariate analysis (p < 0.05). We also determined that an older age (odds ratio [OR] = 6.83), intraoperative lower hemoglobin levels (OR = 6.82), and excessive hemorrhage (OR = 3.62) during surgery were significant variables in the multivariate analysis. CONCLUSION: Clinicians should pay special attention to preventing delirium during the postoperative management of older patients with these risk factors. Furthermore, increasing the hemoglobin levels during surgery may be able to prevent postoperative delirium. PMID- 26143686 TI - Accessibility to editorial information in Oral and Maxillofacial Surgery journals: The authors' point of view. AB - OBJECTIVE: To evaluate the accessibility to editorial information in Oral & Maxillofacial Surgery journals. MATERIAL AND METHODS: A cross-sectional study using the WOS-Web of Science database in three categories: "Surgery," "Otorhinolaryngology," and "Dentistry, Oral Surgery & Medicine" was designed. Journals were filtered by title and classified under three headings: OMFS specialty; OMFS subspecialty and related sciences; and multidisciplinary journals. Specialty scope (OMFS vs. other); impact factor; path for the manuscript; blinding policy; accessibility to reviewers' criteria; and percentage of acceptance. RESULTS: Only 46 of 330 journals met the inclusion criteria. All OMFS journals provided comprehensive information about the review process, compared to 5 of 27 (18.5%) of Oral Surgery and related sciences periodicals. Most specialty journals do not inform about the blind review mode used (20 of 33; 60.6%). Generally, information about the reviewers' assessment criteria is scarce, but is available from all OMFS journals, which also state the percentage of manuscript acceptance (100% vs. 14.8%). CONCLUSIONS: OMFS JCR journals provide adequate information about their editorial process in terms of path for the manuscript, accessibility to reviewers' criteria, and percentage of acceptance. Additional efforts are needed to increase accessibility to information about blinding policy and average time from submission to acceptance. PMID- 26143687 TI - NICE guideline focuses on symptoms to diagnose cancer earlier. PMID- 26143688 TI - Rosacea associated with increased risk of some cancers. PMID- 26143689 TI - Excessive imaging for breast cancer in Ontario. PMID- 26143711 TI - Antimicrobial films based on cellulose-derived hydrocolloids. A synergetic effect of host-guest interactions on quality and functionality. AB - A series of active films based on biodegradable cellulose-derived hydrocolloids capable of controlled release of antimicrobial propionic acid (PA) was prepared. beta-Cyclodextrin (beta-CD), usually used for encapsulation of lipophilic compounds, was utilized in this research to host the hydrophilic PA. It was found that addition of beta-CD to the film forming solutions notably enhanced the hydrocolloid matrix capacity and resulted in up to a ten-fold increase in the amount of uploaded PA. In addition, beta-CD resulted in a two-fold prolongation of the effective PA release duration. beta-CD alone caused undesired effects on the physical, mechanical and morphological properties of the hydrocolloid films. Interestingly, when beta-CD was combined with PA in the film formulation, its undesired effects were significantly subdued. The antifungal activity of the films was demonstrated on fresh harvested wheat grains. Films containing beta-CD and PA were found to be effective in preventing fungal growth on wheat grains. Thus, incorporation of beta-CD and PA in hydrocolloids matrices demonstrated a synergetic effect and resulted in the formation of biodegradable active films that benefit good physical and mechanical properties, high active agent content, prolonged release ability and effective antimicrobial properties. PMID- 26143713 TI - Alterations in markers of coagulation and fibrinolysis in patients with Paroxysmal Nocturnal Hemoglobinuria before and during treatment with eculizumab. AB - BACKGROUND: Paroxysmal Nocturnal Hemoglobinuria is characterized by complement mediated hemolysis and an increased thrombosis risk. Eculizumab, an antibody to complement factor C5, reduces thrombotic risk via unknown mechanisms. Clinical observations suggest that eculizumab has an immediate effect. OBJECTIVES: A better understanding of the mechanism via which eculizumab reduces thrombotic risk by studying its pharmacodynamic effect on coagulation and fibrinolysis. METHODS: We measured microparticles (MP), tissue factor (TF) activity, prothrombin fragment 1+2 (F1+2), D-dimer and simultaneously thrombin and plasmin generation in 55 PNH patients. In 20 patients, parameters were compared before and during eculizumab treatment (at 1 and 2hours, 1, 4 and>=12weeks after commencement). RESULTS: Patients with a history of thrombosis had elevated D dimers (p=0.02) but not MP. Among patients on anticoagulants, those with thrombosis had higher F1+2 concentrations (p=0.003). TF activity was undetectable in plasma MP. Unexpectedly, thrombin peak height and thrombin potential were significantly lower in PNH patients than in healthy controls. Fibrinolysis parameters were normal. During eculizumab treatment D-dimer levels significantly decreased after 1hour (p=0.008) and remained decreased at>=12weeks (p=0.03). F1+2 (p=0.03) and thrombin peak height (p=0.02) in patients not on anticoagulants significantly decreased at>=week 12. MP remained unchanged. CONCLUSIONS: Eculizumab induces an immediate decrease of D-dimer levels but not of other markers. The decrease in thrombin peak height and F1+2 suggests that eculizumab reduces thrombin generation. Elevated D-dimer levels in untreated PNH patients with a history of thrombosis suggest possible value in predicting thrombotic risk. PMID- 26143712 TI - Predictors of venous thromboembolism recurrence, adjusted for treatments and interim exposures: a population-based case-cohort study. AB - BACKGROUND: Predictors of venous thromboembolism (VTE) recurrence are uncertain. OBJECTIVE: To identify predictors of VTE recurrence, adjusted for treatments and interim exposures. MATERIALS AND METHODS: Using Rochester Epidemiology Project resources, all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988-2000, who survived >=1day were followed for first objectively-diagnosed VTE recurrence. For all patients with recurrence, and a random sample of all surviving incident VTE patients (n=415), we collected demographic and baseline characteristics, treatments and interim exposures. In a case-cohort study design, demographic, baseline, treatment and interim exposure characteristics were tested as potential predictors of VTE recurrence using time dependent Cox proportional hazards modeling. RESULTS: Among 1262 incident VTE patients, 306 developed recurrence over 6,440 person-years. Five-year recurrence rates, overall and for cancer-associated, idiopathic and non-cancer secondary VTE, were 24.5%, 43.4%, 27.3% and 18.1%, respectively. In multivariable analysis, interim hospitalization, active cancer, pregnancy, central venous catheter and respiratory infection were associated with increased hazards of recurrence, and warfarin and aspirin were associated with reduced hazards. Adjusting for treatments and these interim risk factors, male sex, baseline active cancer and failure to achieve a therapeutic aPTT in the first 24hours were independently associated with increased hazards of VTE recurrence over the entire follow-up period, while the hazards of recurrence for patient age, chronic lung disease, leg paresis, prior superficial vein thrombosis and idiopathic VTE varied over the follow-up period. CONCLUSIONS: Baseline and interim exposures can stratify VTE recurrence risk and may be useful for directing secondary prophylaxis. PMID- 26143714 TI - Life history lability underlies rapid climate niche evolution in the angiosperm clade Montiaceae. AB - Despite the recent focus on phylogenetic niche conservatism in macroevolutionary studies, many clades have diversified widely along multiple niche dimensions. The factors underlying lineage-specific niche lability are still not well understood. We examined morphological and climate niche evolution in Montiaceae (Caryophyllales), an ecologically variable plant lineage distributed primarily along the mountain chains of the western Americas. Montiaceae inhabit a broader range of temperatures than their relatives, with an increase in the evolutionary rate of temperature niche diversification at the node subtending this clade. Within Montiaceae, life history is highly labile and significantly correlated with temperature, with perennials consistently occurring in cooler environments. This elevated evolutionary lability facilitated repeated shifts between habitats as new environments were created by post-Eocene orogenic events and aridification in the western Americas. The shifts between annual and perennial forms are elaborations of an underlying rosette body plan in most cases, and may involve simple alterations in biomass allocation. Montiaceae stand as another clear counterexample to phylogenetic niche conservatism, and demonstrate a mechanism by which pronounced ecological shifts may occur frequently and rapidly among closely related species. PMID- 26143715 TI - Extreme cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Outcomes from a single tertiary center. AB - BACKGROUND: Multivisceral resection as part of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) may be required in order to achieve optimal debulking. This study aimed to assess perioperative and long-term outcomes of the most extensive CRS/HIPEC procedures. METHODS: All patients who underwent CRS/HIPEC at our institution between March 2007 and July 2014 were retrospectively reviewed. Patients undergoing extreme cytoreduction (n = 50), defined as a resection of >=5 organs or >=3 bowel anastomoses, were compared with patients who underwent less extensive procedures (n = 219). RESULTS: Complete cytoreduction (CC score <=1) was achieved in 76% of the extreme CRS/HIPEC group, which included patients with colorectal cancer (CRC, n = 17), appendiceal adenocarcinoma (n = 20), gastric cancer (n = 6), and low-grade appendiceal neoplasm (n = 3). When compared with other patients undergoing CRS/HIPEC, the extreme CRS/HIPEC group had higher median PCI score, increased intraoperative blood loss, longer duration of surgery and longer hospital stay (all p values < 0.001). Major 30-day morbidity was significantly higher among the extreme CRS/HIPEC group (34% vs. 17.4%, p = 0.008) and there was also a trend towards higher 90-day mortality (12% vs. 5.1%, p = 0.07). Median disease free survival and overall survival in CRC patients undergoing extreme CRS/HIPEC was poorer (4.1 vs. 14.3 months, p = 0.01 and 10.1 vs. 43.8 months, p < 0.001, respectively). Extreme CRS/HIPEC was found to independently predict decreased overall survival in CRC patients. CONCLUSIONS: Extreme multivisceral resection as part of CRS/HIPEC is associated with higher major morbidity and inferior oncologic outcomes; therefore CRS/HIPEC provides the best outcomes in patients with fewer organs involved. PMID- 26143717 TI - A giant abdominal cystic tumour: Mesentery cystic lymphangioma. PMID- 26143716 TI - One-Dimensional Sliding of p53 Along DNA Is Accelerated in the Presence of Ca(2+) or Mg(2+) at Millimolar Concentrations. AB - One-dimensional (1D) sliding of the tumor suppressor p53 along DNA is an essential dynamics required for its efficient search for the binding sites in the genome. To address how the search process of p53 is affected by the changes in the concentration of Mg(2+) and Ca(2+) after the cell damages, we investigated its sliding dynamics at different concentrations of the divalent cations. The 1D sliding trajectories of p53 along the stretched DNA were measured by using single molecule fluorescence microscopy. The averaged diffusion coefficient calculated from the mean square displacement of p53 on DNA increased significantly at the higher concentration of Mg(2+) or Ca(2+), indicating that the divalent cations accelerate the sliding likely by weakening the DNA-p53 interaction. In addition, two distributions were identified in the displacement of the observed trajectories of p53, demonstrating the presence of the fast and slow sliding modes having large and small diffusion coefficients, respectively. A coreless mutant of p53, in which the core domain was deleted, showed only a single mode whose diffusion coefficient is about twice that of the fast mode for the full length p53. Thus, the two modes are likely the result of the tight and loose interactions between the core domain of p53 and DNA. These results demonstrated clearly that the 1D sliding dynamics of p53 is strongly dependent on the concentration of Mg(2+) and Ca(2+), which maintains the search distance of p53 along DNA in cells that lost homeostatic control of the divalent cations. PMID- 26143736 TI - Clinical comparison of botulinum toxin in motor and autonomic disorders: Similarities and differences. AB - Botulinum toxin is a well established, highly effective and safe treatment option for movement disorders and autonomic diseases with excellent long term results. There is increasing evidence that the beneficial effect in both motor and autonomic indication is based on a complex mode of botulinum toxin action modulating efferent as well as afferent nerve fiber activity. In particular, this has been shown for the treatment of dystonia, spasticity and overactive bladder. A unique observation is that botulinum toxin has a markedly longer duration of action in autonomic than in motor disorders for which the reason remains unclear. Although botulinum toxin type B seems to have an initially higher affinity to autonomic nerve endings there is currently no clear evidence that type B is superior to type A in autonomic disorders. The risk of antibody formation probably does not depend on the target tissue injected and seems to be similar for movement disorders and autonomic indications. More research is needed to better understand similarities and differences of treatment outcome in motor and autonomic disorders. PMID- 26143737 TI - Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin. AB - Developmental neurotoxicity of industrial chemicals and pharmaceuticals have been of growing interest in recent years due to the increasing reports of neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD) and autism. Exposure to these substances during early development may lead to adverse behavior effects manifested at a later phase of life. Pesticides are a wide group of chemicals which are still actively used and residues are found in the environment and in food products. The present study investigated the potential developmental neurotoxic effects of two different types of pesticides, endosulfan and cypermethrin, after a single neonatal exposure during a critical period of brain development. Ten-day-old male NMRI mice were administrated an oral dose of endosulfan or cypermethrin (0.1 or 0.5 mg/kg body weight, respectively). Levels of proteins were measured in the neonatal and adult brain, and adult behavioral testing was performed. The results indicate that both pesticides may induce altered levels of neuroproteins, important for normal brain development, and neurobehavioral abnormalities manifested as altered adult spontaneous behavior and ability to habituate to a novel home environment. The neurotoxic behavioral effects were also presentseveral months after the initial testing, indicating long-lasting or even persistent irreversible effects. Also, the present study suggests a possible link between the altered levels of neuroprotein and changes in behavior when exposed during a critical period of brain development. PMID- 26143738 TI - High reactive oxygen species in fibrotic and nonfibrotic skin of patients with diffuse cutaneous systemic sclerosis. AB - Systemic sclerosis (SSc) is a chronic multisystemic connective tissue disease characterized by progressive fibrosis affecting skin and internal organs. Despite serious efforts to unveil the pathogenic mechanisms of SSc, they are still unclear. High levels of reactive oxygen species (ROS) in affected patients have been shown, and ROS are suggested to play a role in fibrosis pathogenesis. In this study we evaluate ROS levels in nonfibrotic and fibrotic skin of patients with SSc and we compare them with those obtained from healthy controls. We enrolled nine SSc patients fulfilling the EULAR/ACR classification criteria and seven healthy controls. Patients included four men and five women with mean age of 46 +/- 10 years. Controls were matched by sex and age. All patients were affected by the diffuse cutaneous form of SSc and the ANA pattern anti-Scl70. Mean disease duration was 7.5 +/- 5 years. Skin involvement was evaluated by modified Rodnan skin score. Skin samples (4-mm punch biopsy) were taken from fibrotic skin and nonfibrotic skin of patients and from healthy controls as well. To detect ROS, specimens were analyzed immediately after sampling by electron paramagnetic resonance spectroscopy. Blood samples were drawn from all patients and controls to assess oxidative stress biomarkers. ROS levels (expressed as median and range, in nmol/L/min/mg of dry weight) were 24.7 (10.9-47.0) in fibrotic skin, 18.7 (7.3-34.0) in nonfibrotic skin, and 7.7 (3.5-13.6) in healthy control skin. ROS levels in fibrotic and nonfibrotic skin of SSc patients were significantly higher than in healthy controls (p = 0.002 and p = 0.009, respectively). ROS levels in fibrotic skin were raised in comparison to nonfibrotic skin, when samples related to each patient were compared (p = 0.01). ROS levels in fibrotic skin were correlated with forced vital capacity (r = 0.75, p = 0.02) and erythrocyte sedimentation rate (r = 0.70, p = 0.04). All other clinical and lab parameters showed no significant correlation. Compared to controls, blood from SSc patients showed lower ascorbate (vitamin C) levels (8 (3.8-9.8) vs 10.5 (9-19.1) mg/L, p = 0.004) and higher lipid peroxides (873.5 (342-1973) vs 422 (105-576) MUmol/L, p = 0.004). Our results indicate the presence of high oxidative stress in both nonfibrotic skin and fibrotic skin of SSc patients, but with higher tendency in the latter. Raised ROS levels in nonfibrotic skin of SSc patients might be a hint of early involvement in skin fibrogenesis. However, a longitudinal prospective study is necessary for such proof. PMID- 26143739 TI - Fluorophore ATCUN complexes: combining agent and probe for oxidative DNA cleavage. AB - DNA can be oxidatively cleaved by copper complexes of the ATCUN peptide (amino terminal Cu(II)- and Ni(II)-binding motif). In order to investigate the fate of the metal ion throughout this process, we have exploited quenching/dequenching effects of conjugated fluorophores. PMID- 26143741 TI - Marine n-3 polyunsaturated fatty acids lower plasma proprotein convertase subtilisin kexin type 9 levels in pre- and postmenopausal women: A randomised study. AB - OBJECTIVE: To investigate whether a supplement of 2.2g of marine n-3 polyunsaturated fatty acids (PUFA) influences plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels in pre- and postmenopausal women. METHODS: Ninety-two healthy women were randomly assigned to consume 2.2g marine n-3 PUFA or a control oil (thistle oil) daily for 12 weeks. Adipose tissue, a long-term marker of dietary intake of seafood was collected at baseline and blood samples were drawn at baseline and after 12 weeks of supplement intake. RESULTS: Plasma PCSK9 levels were significantly reduced by 11.4% for premenopausal women and 9.8% for postmenopausal women after the supplement of 2.2g of marine n-3 PUFA compared with control oil. The mean change of plasma PCSK9 levels between participants receiving marine n-3 PUFA and control oil was 16.1% for premenopausal women and 13.1% for postmenopausal women. There was, however, no correlation between baseline levels of plasma PCSK9 and the fatty acid content of marine n-3 PUFA in adipose tissue. CONCLUSION: This study showed that 2.2g marine n-3 PUFA reduce plasma PCSK9 levels in both pre- and postmenopausal women. PMID- 26143740 TI - Prolonged physiological reactivity and loss: Association of pupillary reactivity with negative thinking and feelings. AB - Prolonged psychophysiological reactions to negative information have long been associated with negative thinking and feeling. This association is operationalized in the RDoC negative affect construct of loss, which is nominally indexed by prolonged physiological reactivity, cognitive loss-related constructs such as rumination and guilt, and more feeling-related constructs such as sadness, crying, and anhedonia. These associations have not been tested explicitly. If thinking and feeling aspects of loss reflect different physiological mechanisms, as might be suggested by their putative neurobiology, different intervention pathways might be suggested. Here we examined the extent to which self-reported negative thinking and feeling constructs were associated with prolonged pupillary reactivity following negative words and a subsequent cognitive distractor in a diverse heterogeneously diagnosed sample of N=84 participants. We also considered indices of abuse and variables associated with borderline personality disorder as possible moderators. Consistently, feeling related negative affect constructs were related to prolonged pupillary reactivity during the distractor after a negative stimulus whereas thinking-related constructs were not. These data suggest that people who have sustained physiological reactions to emotional stimuli may be more strongly characterized by non-linguistic negative feelings than explicit cognitions related to loss. Sustained physiological reactions could reflect efforts to regulate feeling states. In contrast to cognitive and affective variables, abuse was associated with decreased physiological reactivity, consistent with decreased neural engagement. Interventions that target mechanisms underlying feelings and their regulation may be more mechanistically specific to sustained reactivity than those which directly address cognitions. PMID- 26143742 TI - Fatigue damage to pig erythrocytes during repeated swelling and shrinkage. AB - During the removal of cryoprotectants from cryopreserved-thawed blood with the dialysis-based or dilution-filtration method, due to the change in the extracellular osmolality, erythrocytes usually undergo repeated swelling and shrinkage. However, the erythrocyte fatigue damage induced by this repeated volume change has not yet been studied. In this work, by successively loading hypotonic and hypertonic solutions, we mimicked the repeated swelling and shrinkage of pig erythrocytes and then examined the effect of the number of cycle loops on the steady-state volume and the mortality of the pig erythrocytes. The results suggest that because of cell leakage in the swelling process, the steady state volume of the pig erythrocytes after one cycle is smaller than the volume before the cycle, even though the cell performs a self-protective regulatory procedure. If the number of cycle loops is increased, the repeated swelling and shrinkage will cause a continuous decrease in the steady-state volume, and the ability of the pig erythrocytes to resist osmotic damage will decrease; as a result, the mortality of the pig erythrocytes increases as the number of cycle loops increases. The viability of the cells is also affected by the hypotonic and isotonic processing times: a short processing time may contribute to a decrease in the mortality of the pig erythrocytes. This work is of significance to optimizing the process of removing cryoprotectants. PMID- 26143743 TI - The impact of weight loss and low BMI on mortality of nursing home residents - Results from the nutritionDay in nursing homes. AB - BACKGROUND: Weight loss and low body-mass-index (BMI) are well-known risk factors for mortality among older persons. Both items represent a reduced nutritional state but their nature is different. It is, however, unclear which of these factors is more important for prognosis and if there is interference or interaction between them. OBJECTIVE: To measure the prevalence of low BMI and weight loss in nursing home residents and to analyze their impact on mortality. METHODS: The nutritionDay in nursing homes is an international annual one-day cross sectional survey evaluating malnutrition and 6-months mortality. The data collected from 2007 to 2012 were analyzed. The mortality risk due to a BMI <20 kg/m(2) and weight loss >5 kg was calculated by logistic regression analysis with adjustment for confounding factors. RESULTS: In total, 10,298 residents with a mean age of 85 years (78% female) from 191 nursing homes in 13 countries were included in the analysis. Eighteen percent (17.7%) had a low BMI < 20 kg/m(2), and 11.3% lost > 5 kg of body weight in the previous year. Low BMI <20 kg/m(2) and weight loss >5 kg were both independent and significant risk factors for 6 months mortality (OR 1.7 and 1.5; p < 0.001 in the adjusted model). In comparison to the effect size of low BMI and weight loss alone, the interaction of both factors was substantial (OR = 1.4; p = 0.056). The average 6-months mortality was 13.8%. Subjects with BMI >=20 kg/m(2) without weight loss >5 kg presented the lowest mortality of 11.2%. In subjects with one of the two features, weight loss >5 kg or low BMI <20 kg/m(2), mortality was significantly increased to 17.4% and 19.8%, respectively. However, if both features were present simultaneously the mortality increased disproportionally to 35.7% (OR 3.5; p < 0.001). In addition, this study presents an overlap and a strong dose-effect relationship of both items with regard to the 6-month mortality. CONCLUSION: A BMI <20 kg/m(2) and weight loss >5 kg in one year are both independent and equally relevant risk factors for the 6-months mortality of nursing home residents aged 65 years or older. For this reason weight loss should be avoided and residents with a low BMI and weight loss should receive particular attention and nutritional care. PMID- 26143744 TI - The prevalence of malnutrition according to the new ESPEN definition in four diverse populations. AB - BACKGROUND & AIMS: Consensus on the definition of malnutrition has not yet been reached. Recently, The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed a consensus definition of malnutrition. The aim of the present study was to describe the prevalence of malnutrition according to the ESPEN definition in four diverse populations. METHODS: In total, 349 acutely ill middle aged patients, 135 geriatric outpatients, 306 healthy old individuals and 179 healthy young individuals were included in the study. Subjects were screened for risk of malnutrition using the SNAQ. The ESPEN definition of malnutrition, i.e. low BMI (< 18.5 kg/m(2)) or a combination of unintentional weight loss and low FFMI or low BMI was applied to all subjects. RESULTS: Screening identified 0, 0.5, 10 and 30% of the healthy young, the healthy old, the geriatric outpatients and the acutely ill middle-aged patients as being at risk of malnutrition. The prevalence of malnutrition ranged from 0% in the healthy young, 0.5% in healthy old individuals, 6% in the geriatric outpatients to 14% in the acutely ill middle aged patients. Prevalence of low FFMI was observed in all four populations (14 33%), but concurred less frequently with weight loss (0-13%). CONCLUSIONS: Using the ESPEN definition, 0%-14% malnutrition was found in the diverse populations. Further work is needed to fully address the validity of a two-step approach, including risk assessment as an initial step in screening and defining malnutrition. Furthermore, assessing the predictive validity of the ESPEN definition is needed. PMID- 26143745 TI - Automated assessment of pain in rats using a voluntarily accessed static weight bearing test. AB - The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. NEW METHODS: We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). RESULTS: Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. CONCLUSION: The VASIC device should enhance the hands-free parallel collection of unbiased weight bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. PMID- 26143747 TI - One more wheel for a processing machine. PMID- 26143666 TI - Subretinal Hyperreflective Material in the Comparison of Age-Related Macular Degeneration Treatments Trials. AB - PURPOSE: To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). DESIGN: Prospective cohort study within a randomized clinical trial. PARTICIPANTS: The 1185 CATT participants. METHODS: Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks. MAIN OUTCOME MEASURES: Presence of SHRM, as well as location and size, and associations with VA, scar, and GA. RESULTS: Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 MUm, 120 MUm, and 122 MUm, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05). CONCLUSIONS: In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker. PMID- 26143746 TI - Distinct Neurodegenerative Changes in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia Linked to Mutant TAU Protein. AB - Frontotemporal dementia (FTD) is a frequent form of early-onset dementia and can be caused by mutations in MAPT encoding the microtubule-associated protein TAU. Because of limited availability of neural cells from patients' brains, the underlying mechanisms of neurodegeneration in FTD are poorly understood. Here, we derived induced pluripotent stem cells (iPSCs) from individuals with FTD associated MAPT mutations and differentiated them into mature neurons. Patient iPSC-derived neurons demonstrated pronounced TAU pathology with increased fragmentation and phospho-TAU immunoreactivity, decreased neurite extension, and increased but reversible oxidative stress response to inhibition of mitochondrial respiration. Furthermore, FTD neurons showed an activation of the unfolded protein response, and a transcriptome analysis demonstrated distinct, disease associated gene expression profiles. These findings indicate distinct neurodegenerative changes in FTD caused by mutant TAU and highlight the unique opportunity to use neurons differentiated from patient-specific iPSCs to identify potential targets for drug screening purposes and therapeutic intervention. PMID- 26143748 TI - Ferroptosis in p53-dependent oncosuppression and organismal homeostasis. PMID- 26143749 TI - Deducing acidification rates based on short-term time series. AB - We show that, statistically, the simple linear regression (SLR)-determined rate of temporal change in seawater pH (betapH), the so-called acidification rate, can be expressed as a linear combination of a constant (the estimated rate of temporal change in pH) and SLR-determined rates of temporal changes in other variables (deviation largely due to various sampling distributions), despite complications due to different observation durations and temporal sampling distributions. Observations show that five time series data sets worldwide, with observation times from 9 to 23 years, have yielded betapH values that vary from 1.61 * 10(-3) to -2.5 * 10(-3) pH unit yr(-1). After correcting for the deviation, these data now all yield an acidification rate similar to what is expected under the air-sea CO2 equilibrium (-1.6 * 10(-3) ~ -1.8 * 10(-3) pH unit yr(-1)). Although long-term time series stations may have evenly distributed datasets, shorter time series may suffer large errors which are correctable by this method. PMID- 26143751 TI - Mechanical degradation of graphene by epoxidation: insights from first-principles calculations. AB - Oxidation is a major cause for the degradation of materials including graphene, where epoxidation (forming the C-O-C bond) is very common. In addition, graphene oxide, in which the epoxy group is one of the two major functional groups (the other is hydroxy), is an important precursor material used for the bulk synthesis of graphene sheets. Information about the mechanical stabilities, non-linear elastic properties, and elastic limits under various strain components is invaluable for application of these nanomaterials. Here, we investigate the mechanical properties of the epoxidized graphene in ordered graphene oxide, namely C6O1, C6O2, and C6O3, representing the carbon : oxygen ratios of 6 : 1, 3 : 1, and 2 : 1, respectively, using first-principles calculations within the framework of density functional theory. We predict a reduction of Young's modulus of graphene by a factor of 20%, 23%, and 27% for C6O1, C6O2, and C6O3, respectively, indicating a monotonic degradation with respect to epoxidation. However, there is no clear trend for Poisson's ratio, implying that the local atomic configurations are dominant over oxygen concentrations in determining the Poisson ratio. Our computed high order elastic constants are good for the design of graphene oxide based flexible transparent electronics. PMID- 26143752 TI - Self-healing hydrogels containing reversible oxime crosslinks. AB - Self-healing oxime-functional hydrogels have been developed that undergo a reversible gel-to-sol transition via oxime exchange under acidic conditions. Keto functional copolymers were prepared by conventional radical polymerization of N,N dimethylacrylamide (DMA) and diacetone acrylamide (DAA). The resulting water soluble copolymers (P(DMA-stat-DAA)) were chemically crosslinked with difunctional alkoxyamines to obtain hydrogels via oxime formation. Gel-to-sol transitions were induced by the addition of excess monofunctional alkoxyamines to promote competitive oxime exchange under acidic conditions at 25 degrees C. The hydrogel could autonomously heal after it was damaged due to the dynamic nature of the oxime crosslinks. In addition to their chemo-responsive behavior, the P(DMA-stat-DAA) copolymers exhibit cloud points which vary with the DAA content in the copolymers. This thermo-responsive behavior of the P(DMA-stat-DAA) was utilized to form physical hydrogels above their cloud point. Therefore, these materials can either form dynamic-covalent or physically-crosslinked gels, both of which demonstrate reversible gelation behavior. PMID- 26143753 TI - Population structure and genotypic variation of Crataegus pontica inferred by molecular markers. AB - Information about the natural patterns of genetic variability and their evolutionary bases are of fundamental practical importance for sustainable forest management and conservation. In the present study, the genetic diversity of 164 individuals from fourteen natural populations of Crataegus pontica K.Koch was assessed for the first time using three genome-based molecular techniques; inter retrotransposon amplified polymorphism (IRAP); inter-simple sequence repeats (ISSR) and start codon targeted (SCoT) polymorphism. IRAP, ISSR and SCoT analyses yielded 126, 254 and 199 scorable amplified bands, respectively, of which 90.48, 93.37 and 83.78% were polymorphic. ISSR revealed efficiency over IRAP and SCoT due to high effective multiplex ratio, marker index and resolving power. The dendrograms based on the markers used and combined data divided individuals into three major clusters. The correlation between the coefficient matrices for the IRAP, ISSR and SCoT data was significant. A higher level of genetic variation was observed within populations than among populations based on the markers used. The lower divergence levels depicted among the studied populations could be seen as evidence of gene flow. The promotion of gene exchange will be very beneficial to conserve and utilize the enormous genetic variability. PMID- 26143750 TI - Forward genetic screen for auxin-deficient mutants by cytokinin. AB - Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, ethylene, N-1-naphthylphthalamic acid (NPA) or cytokinin (CK), there is still a lack of robust markers for systematically isolating such mutants. We hypothesized that a potentially suitable phenotypic marker is root curling induced by CK, as observed in the auxin biosynthesis mutant CK-induced root curling 1 / tryptophan aminotransferase of Arabidopsis 1 (ckrc1/taa1). Phenotypic observations, genetic analyses and biochemical complementation tests of Arabidopsis seedlings displaying the trait in large-scale genetic screens showed that it can facilitate isolation of mutants with perturbations in auxin biosynthesis, transport and signaling. However, unlike transport/signaling mutants, the curled (or wavy) root phenotypes of auxin-deficient mutants were significantly induced by CKs and could be rescued by exogenous auxins. Mutants allelic to several known auxin biosynthesis mutants were re-isolated, but several new classes of auxin-deficient mutants were also isolated. The findings show that CK-induced root curling provides an effective marker for discovering genes involved in auxin biosynthesis or homeostasis. PMID- 26143754 TI - Downregulation of miR-363 increases drug resistance in cisplatin-treated HepG2 by dysregulating Mcl-1. AB - Systemic therapy with cytotoxic agents provides marginal benefit in hepatocellular carcinoma (HCC) treatment especially for patients with advanced HCC. Cisplatin is one of the most active cytotoxic agents for HCC treatment. However, acquisition of cisplatin resistance is common, and one important underlying mechanism of such resistance is apoptosis-resistance. In this study, we found that miR-363 levels were significantly decreased in HCC patients treated with cisplatin-based chemotherapy. MiR-363 levels were also lower in cisplatin resistant HepG2 (HepG2-R) cells than in HepG2 cells. Exogenous miR-363 significantly overcame cisplatin resistance in HepG2-R cells, whereas miR-363 knockdown increased the cell viability during cisplatin treatment. We further demonstrated that miR-363 directly targeted to Mcl-1 3'-UTR (3'-Untranslated Regions). Downregulation of miR-363 resulted in upregulation of Mcl-1 which is a key member of anti-apoptotic Bcl-2 family and increased drug resistance. We finally demonstrated that miR-363 decreased cisplatin resistance of HCC cell, partly by targeting Mcl-1. These data suggest that the combination of miR-363 and cisplatin may represent a novel approach in treatment for HCC, thus offering a new target for chemotherapy of HCC. PMID- 26143808 TI - High coverage adsorption and co-adsorption of CO and H2 on Ru(0001) from DFT and thermodynamics. AB - The adsorption and co-adsorption of CO and H2 at different coverages on p(4 * 4) Ru(0001) have been computed using periodic density functional theory (GGA-RPBE) and atomistic thermodynamics. Only molecular CO adsorption is possible and the saturation coverage is 0.75 ML (nCO = 12) with CO molecules co-adsorbed at different sites and has a hexagonal adsorption pattern as found by low energy electron diffraction. Only dissociative H2 adsorption is possible and the saturation coverage is 1 ML (nH = 16) with H atoms at face-centered cubic sites. The computed CO and H2 desorption patterns and temperatures agree reasonably with the experiments under ultrahigh vacuum conditions. For CO and H2 co-adsorption (nCO + mH2; n = 1-6 and m = 7, 6, 5, 5, 3, 1), CO pre-coverage affects H adsorption strongly, and each pre-adsorbed CO molecule blocks 2H adsorption sites and H2 does not adsorb on the surface with CO pre-coverage larger than 0.44 ML (nCO = 7); all these are in full agreement with the experiments under ultrahigh vacuum conditions. Our results provide the basis for exploring the mechanisms of catalytic conversion of synthesis gas. PMID- 26143861 TI - The role of genetic testing in unexplained sudden death. AB - Most sudden deaths are because of a cardiac etiology and are termed sudden cardiac death (SCD). In younger individuals coronary artery disease is less prevalent and cardiac genetic disorders are more common. If sudden death is unexplained despite an appropriate autopsy and toxicologic assessment the term sudden arrhythmic death syndrome (SADS) may be used. This is an umbrella term and common underlying etiologies are primary arrhythmia syndromes with a familial basis such as Brugada syndrome, long QT syndrome, and subtle forms of cardiomyopathy. The first clinical presentation of these conditions is often SCD, which makes identification, screening, and risk stratification crucial to avert further deaths. This review will focus on genetic testing in the context of family screening. It will address the role of the "molecular autopsy" alongside current postmortem practices in the evaluation of SADS deaths. We describe the current data underlying genetic testing in these conditions, explore the potential for next-generation sequencing, and discuss the inherent diagnostic problems in determination of pathogenicity. PMID- 26143862 TI - Non-nitric oxide based metallovasodilators: synthesis, reactivity and biological studies. AB - There is an increasing number of compounds developed to target one or more pathways involved in vasodilation. Some studies conducted with azaindole and indazole derivatives showed cardiovascular activity associated with these compounds. Fast and easy structural modification of these organic molecules can be achieved using metal complexes promoting a much larger spatial change than organic strategies, potentially leading to novel drugs. Here, we have prepared a series of complexes with a formula cis-[RuCl(L)(bpy)(2)]PF(6), where L = 7 azaindole (ain), 5-azaindole (5-ain), 4-azaindole (4-ain), indazole (indz), benzimidazole (bzim) or quinoline (qui), which were characterized by spectroscopic and electrochemical techniques (CV, DPV). These compounds showed reasonable stability exhibiting photoreactivity only at low wavelength along with superoxide scavenger activity. Cytotoxicity assays indicated their low activity preliminarily supporting in vivo application. Interestingly, vasodilation assays conducted in rat aorta exhibited great activity that largely improved compared to free ligands and even better than the well-studied organic compound (BAY 41 42272), with IC(50) reaching 55 nM. These results have validated this strategy opening new opportunities to further develop cardiovascular agents based on metallo-bicyclic rings. PMID- 26143863 TI - Single crystalline tantalum oxychloride microcubes: controllable synthesis, formation mechanism and enhanced photocatalytic hydrogen production activity. AB - Single crystalline microcubes of a new tantalum compound, tantalum oxychloride (TaO2.18Cl0.64), have been fabricated hydrothermally in a concentrated aqueous solution of hydrochloric acid and acetic acid. They contain a superstructure and exhibit remarkably enhanced photocatalytic activities for hydrogen production due to the improved light harvest and facilitated charge transport. PMID- 26143864 TI - Host immune responses to experimental infection of Plasmodium relictum (lineage SGS1) in domestic canaries (Serinus canaria). AB - Understanding the complexity of host immune responses to parasite infection requires controlled experiments that can inform observational field studies. Birds and their malaria parasites provide a useful model for understanding host parasite relationships, but this model lacks a well-described experimental context for how hosts respond immunologically to infection. Here, ten canaries (Serinus canaria) were infected with the avian malaria parasite Plasmodium relictum (lineage SGS1) in a controlled laboratory setting with ten uninfected (control) birds. A suite of immunological blood parameters, including the concentration of four white blood cell types, the concentration of the acute phase protein haptoglobin, and the bacteria-killing ability of blood plasma, were repeatedly measured over a 25-day period covering the acute phase of a primary infection by P. relictum. Three infected and one control bird died during the course of the experiment. A multivariate statistical analysis of the immune indices revealed significant differences between infected and uninfected individuals between 5 and 14 days postinfection (dpi). Group differences corresponded to reduced concentrations of lymphocytes (5 dpi), heterophils (8 dpi), and monocytes (11 and 14 dpi), and an increase in haptoglobin (14 dpi), in infected birds relative to uninfected controls, and no change in bacteria killing. Upon re-running the analysis with only the surviving birds, immunological differences between infected and control birds shifted to between 11 and 18 dpi. However, there were no clear correlates relating immune parameters to the likelihood of surviving the infection. The results presented here demonstrate the dynamic and complex nature of avian immune function during the acute phase of malaria infection and provide a context for studies investigating immune function in wild birds. PMID- 26143865 TI - Carvacrol as a potent natural acaricide against Dermanyssus gallinae. AB - Resistance to conventional synthetic pesticides has been widely reported in Dermanyssus gallinae in poultry production systems. Introducing novel acaricides to poultry industry today is more urgent than ever. Research in this field recently focused on plants and plant-derived compounds as acaricides. In the present study, acaricidal activity of three plant bioactive components, carvacrol, thymol, and farnesol, was assessed against D. gallinae and compared with synthetic pesticide permethrin. Mode of acaricidal action was determined by contact toxicity and fumigant toxicity bioassays. Except farnesol which did not cause any mortality, carvacrol and thymol were found to be toxic to D. gallinae with LD50 values of 1 and 3.15 MUg/cm(3), respectively. Permethrin gave the LD50 value of 31.95 MUg/cm(3) which was less efficient than carvacrol and thymol. In fumigant toxicity bioassay, mortality rate in carvacrol- and thymol-treated groups in closed method was significantly higher than the open one. On the other hand, permethrin exhibited poor fumigant toxicity as there was no statistically significant difference between mortality rate in open and closed methods. These findings revealed that mechanism of acaricidal activity of carvacrol and thymol but not permethrin was mainly due to fumigant action. Results of the present study suggested that carvacrol and thymol, especially carvacrol, can be developed as a novel potent bioacaricide against D. gallinae. PMID- 26143866 TI - Experimental infections of rabbits with proliferative and latent stages of Besnoitia besnoiti. AB - Cattle besnoitiosis due to Besnoitia besnoiti is spreading across Europe and is responsible for severe economic losses in newly infected herds. Experimentally speaking, rabbits have been found to be susceptible to this parasite. The adaptation of B. besnoiti to rabbits may offer a new, easier and cheaper model of investigation for this disease. This study compared the virulence between tachyzoites and bradyzoites of B. besnoiti in rabbits. Eighteen New Zealand rabbits were allocated into three groups of six animals each. The rabbits from the control (group C), "tachyzoite" (group T) and "bradyzoite" (group B) groups were subcutaneously injected in the right flank with 66 MUg of ovalbumin, 6.10(6) tachyzoites (125th passage on Vero cells) and 6.10(6) bradyzoites (collected from a natural infected cow) of B. besnoiti, respectively. Clinical follow-up and blood sampling for serological survey and qPCR were performed during 10 weeks until euthanasia. Molecular and immunohistochemistry examination was achieved on 25 samples of tissue per rabbit. Seroconversion occurred in group T without any clinical signs. Rabbits of group B exhibited a febrile condition (temperature above 40 degrees C from day 8 to day 11 following injection) with positive qPCR in blood. Cysts of B. besnoiti were found on skin samples and organs of rabbits from group B in tissue explored with threshold cycle (Ct) values below 30. These results suggest a higher virulence of bradyzoites in rabbits than Vero cell cultivated tachyzoites. The proposed model could be used to assess the in vivo effectiveness of vaccine or drugs against cattle besnoitiosis. PMID- 26143867 TI - Electrical probing of field-driven cascading quantized transitions of skyrmion cluster states in MnSi nanowires. AB - Magnetic skyrmions are topologically stable whirlpool-like spin textures that offer great promise as information carriers for future spintronic devices. To enable such applications, particular attention has been focused on the properties of skyrmions in highly confined geometries such as one-dimensional nanowires. Hitherto, it is still experimentally unclear what happens when the width of the nanowire is comparable to that of a single skyrmion. Here, we achieve this by measuring the magnetoresistance in ultra-narrow MnSi nanowires. We observe quantized jumps in magnetoresistance versus magnetic field curves. By tracking the size dependence of the jump number, we infer that skyrmions are assembled into cluster states with a tunable number of skyrmions, in agreement with the Monte Carlo simulations. Our results enable an electric reading of the number of skyrmions in the cluster states, thus laying a solid foundation to realize skyrmion-based memory devices. PMID- 26143868 TI - Erratum to: Analysis of gene expression during aging of CGNs in culture: implication of SLIT2 and NPY in senescence. PMID- 26143870 TI - Beyond Homozygosity Mapping: Family-Control analysis based on Hamming distance for prioritizing variants in exome sequencing. AB - A major challenge in current exome sequencing in autosomal recessive (AR) families is the lack of an effective method to prioritize single-nucleotide variants (SNVs). AR families are generally too small for linkage analysis, and length of homozygous regions is unreliable for identification of causative variants. Various common filtering steps usually result in a list of candidate variants that cannot be narrowed down further or ranked. To prioritize shortlisted SNVs we consider each homozygous candidate variant together with a set of SNVs flanking it. We compare the resulting array of genotypes between an affected family member and a number of control individuals and argue that, in a family, differences between family member and controls should be larger for a pathogenic variant and SNVs flanking it than for a random variant. We assess differences between arrays in two individuals by the Hamming distance and develop a suitable test statistic, which is expected to be large for a causative variant and flanking SNVs. We prioritize candidate variants based on this statistic and applied our approach to six patients with known pathogenic variants and found these to be in the top 2 to 10 percentiles of ranks. PMID- 26143886 TI - Multidimensional High-Resolution Magic Angle Spinning and Solution-State NMR Characterization of (13)C-labeled Plant Metabolites and Lignocellulose. AB - Lignocellulose, which includes mainly cellulose, hemicellulose, and lignin, is a potential resource for the production of chemicals and for other applications. For effective production of materials derived from biomass, it is important to characterize the metabolites and polymeric components of the biomass. Nuclear magnetic resonance (NMR) spectroscopy has been used to identify biomass components; however, the NMR spectra of metabolites and lignocellulose components are ambiguously assigned in many cases due to overlapping chemical shift peaks. Using our (13)C-labeling technique in higher plants such as poplar samples, we demonstrated that overlapping peaks could be resolved by three-dimensional NMR experiments to more accurately assign chemical shifts compared with two dimensional NMR measurements. Metabolites of the (13)C-poplar were measured by high-resolution magic angle spinning NMR spectroscopy, which allows sample analysis without solvent extraction, while lignocellulose components of the (13)C poplar dissolved in dimethylsulfoxide/pyridine solvent were analyzed by solution state NMR techniques. Using these methods, we were able to unambiguously assign chemical shifts of small and macromolecular components in (13)C-poplar samples. Furthermore, using samples of less than 5 mg, we could differentiate between two kinds of genes that were overexpressed in poplar samples, which produced clearly modified plant cell wall components. PMID- 26143888 TI - Modulating the interaction between gold and TiO2 nanowires for enhanced solar driven photoelectrocatalytic hydrogen generation. AB - The interaction strength of Au nanoparticles with pristine and nitrogen doped TiO2 nanowire surfaces was analysed using density functional theory and their significance in enhancing the solar driven photoelectrocatalytic properties was elucidated. In this article, we prepared 4-dimethylaminopyridine capped Au nanoparticle decorated TiO2 nanowire systems. The density functional theory calculations show {101} facets of TiO2 as the preferred phase for dimethylaminopyridine-Au nanoparticles anchoring with a binding energy of -8.282 kcal mol(-1). Besides, the interaction strength of Au nanoparticles was enhanced nearly four-fold (-35.559 kcal mol(-1)) at {101} facets via nitrogen doping, which indeed amplified the Au nanoparticle density on nitrided TiO2. The Au coated nitrogen doped TiO2 (N-TiO2-Au) hybrid electrodes show higher absorbance owing to the light scattering effect of Au nanoparticles. In addition, N-TiO2-Au hybrid electrodes block the charge leakage from the electrode to the electrolyte and thus reduce the charge recombination at the electrode/electrolyte interface. Despite the beneficial band narrowing effect of nitrogen in TiO2 on the electrochemical and visible light activity in N-TiO2-Au hybrid electrodes, it results in low photocurrent generation at higher Au NP loading (3.4 * 10(-7) M) due to light blocking the N-TiO2 surface. Strikingly, even with a ten-fold lower Au NP loading (0.34 * 10(-7) M), the synergistic effects of nitrogen doping and Au NPs on the N-TiO2-Au hybrid system yield high photocurrent compared to TiO2 and TiO2-Au electrodes. As a result, the N-TiO2-Au electrode produces nearly 270 MUmol h(-1) cm(-2) hydrogen, which is nearly two-fold higher than the pristine TiO2 counterpart. The implications of these findings for the design of efficient hybrid photoelectrocatalytic electrodes are discussed. PMID- 26143887 TI - Single molecular force across single integrins dictates cell spreading. AB - Cells' ability to sense and interpret mechanical signals from the extracellular milieu modulates the degree of cell spreading. Yet how cells detect such signals and activate downstream signaling at the molecular level remain elusive. Herein, we utilize tension gauge tether (TGT) platform to investigate the underlying molecular mechanism of cell spreading. Our data from both differentiated cells of cancerous and non-cancerous origin show that for the same stiff underlying glass substrates and for same ligand density it is the molecular forces across single integrins that ultimately determine cell spreading responses. Furthermore, by decoupling molecular stiffness and molecular tension we demonstrate that molecular stiffness has little influence on cell spreading. Our data provide strong evidence that links molecular forces at the cell-substrate interface to the degree of cell spreading. PMID- 26143911 TI - Photocatalytic water reduction from a noble-metal-free molecular dyad based on a thienyl-expanded BODIPY photosensitizer. AB - A noble-metal-free molecular dyad was constructed by anchoring a thienyl-expanded BODIPY photosensitizer (PS) to a cobaloxime catalyst, which gives a 2.5-fold increase in the TON, and a 3-fold enhancement in the quantum efficiency as compared to the multicomponent catalytic system for the generation of hydrogen via the reduction of water. The stability of PS was expected to improve by introducing the thienyl moiety into the BODIPY core. PMID- 26143912 TI - Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX. AB - Fifteen per cent of cancers maintain telomere length independently of telomerase by the homologous recombination (HR)-associated alternative lengthening of telomeres (ALT) pathway. A unifying feature of these tumours are mutations in ATRX. Here we show that expression of ectopic ATRX triggers a suppression of the pathway and telomere shortening. Importantly ATRX-mediated ALT suppression is dependent on the histone chaperone DAXX. Re-expression of ATRX is associated with a reduction in replication fork stalling, a known trigger for HR and loss of MRN from telomeres. A G-quadruplex stabilizer partially reverses the effect of ATRX, inferring ATRX may normally facilitate replication through these sequences that, if they persist, promote ALT. We propose that defective telomere chromatinization through loss of ATRX promotes the persistence of aberrant DNA secondary structures, which in turn present a barrier to DNA replication, leading to replication fork stalling, collapse, HR and subsequent recombination-mediated telomere synthesis in ALT cancers. PMID- 26143913 TI - Protein secondary-structure description with a coarse-grained model. AB - A coarse-grained geometrical model for protein secondary-structure description and analysis is presented which uses only the positions of the C(alpha) atoms. A space curve connecting these positions by piecewise polynomial interpolation is constructed and the folding of the protein backbone is described by a succession of screw motions linking the Frenet frames at consecutive C(alpha) positions. Using the ASTRAL subset of the SCOPe database of protein structures, thresholds are derived for the screw parameters of secondary-structure elements and demonstrate that the latter can be reliably assigned on the basis of a C(alpha) model. For this purpose, a comparative study with the widely used DSSP (Define Secondary Structure of Proteins) algorithm was performed and it was shown that the parameter distribution corresponding to the ensemble of all pure C(alpha) structures in the RCSB Protein Data Bank matches that of the ASTRAL database. It is expected that this approach will be useful in the development of structure refinement techniques for low-resolution data. PMID- 26143915 TI - S-SAD phasing of monoclinic histidine kinase from Brucella abortus combining data from multiple crystals and orientations: an example of data-collection strategy and a posteriori analysis of different data combinations. AB - The histidine kinase (HK) domain belonging to the light-oxygen-voltage histidine kinase (LOV-HK) from Brucella abortus is a member of the HWE family, for which no structural information is available, and has low sequence identity (20%) to the closest HK present in the PDB. The 'off-edge' S-SAD method in macromolecular X ray crystallography was used to solve the structure of the HK domain from LOV-HK at low resolution from crystals in a low-symmetry space group (P21) and with four copies in the asymmetric unit (~108 kDa). Data were collected both from multiple crystals (diffraction limit varying from 2.90 to 3.25 A) and from multiple orientations of the same crystal, using the kappa-geometry goniostat on SOLEIL beamline PROXIMA 1, to obtain 'true redundancy'. Data from three different crystals were combined for structure determination. An optimized HK construct bearing a shorter cloning artifact yielded crystals that diffracted X-rays to 2.51 A resolution and that were used for final refinement of the model. Moreover, a thorough a posteriori analysis using several different combinations of data sets allowed us to investigate the impact of the data-collection strategy on the success of the structure determination. PMID- 26143914 TI - Two high-mobility group box domains act together to underwind and kink DNA. AB - High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A is thought to be responsible for the majority of HMGB1-DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 A. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA. PMID- 26143916 TI - Protonation and geometry of histidine rings. AB - The presence of H atoms connected to either or both of the two N atoms of the imidazole moiety in a histidine residue affects the geometry of the five-membered ring. Analysis of the imidazole moieties found in histidine residues of atomic resolution protein crystal structures in the Protein Data Bank (PDB), and in small-molecule structures retrieved from the Cambridge Structural Database (CSD), identified characteristic patterns of bond lengths and angles related to the protonation state of the imidazole moiety. Using discriminant analysis, two functions could be defined, corresponding to linear combinations of the four most sensitive stereochemical parameters, two bond lengths (ND1-CE1 and CE1-NE2) and two endocyclic angles (-ND1- and -NE2-), that uniquely identify the protonation states of all imidazole moieties in the CSD and can be used to predict which N atom(s) of the histidine side chains in protein structures are protonated. Updated geometrical restraint target values are proposed for differently protonated histidine side chains for use in macromolecular refinement. PMID- 26143917 TI - New insights into the enzymatic mechanism of human chitotriosidase (CHIT1) catalytic domain by atomic resolution X-ray diffraction and hybrid QM/MM. AB - Chitotriosidase (CHIT1) is a human chitinase belonging to the highly conserved glycosyl hydrolase family 18 (GH18). GH18 enzymes hydrolyze chitin, an N acetylglucosamine polymer synthesized by lower organisms for structural purposes. Recently, CHIT1 has attracted attention owing to its upregulation in immune system disorders and as a marker of Gaucher disease. The 39 kDa catalytic domain shows a conserved cluster of three acidic residues, Glu140, Asp138 and Asp136, involved in the hydrolysis reaction. Under an excess concentration of substrate, CHIT1 and other homologues perform an additional activity, transglycosylation. To understand the catalytic mechanism of GH18 chitinases and the dual enzymatic activity, the structure and mechanism of CHIT1 were analyzed in detail. The resolution of the crystals of the catalytic domain was improved from 1.65 A (PDB entry 1waw) to 0.95-1.10 A for the apo and pseudo-apo forms and the complex with chitobiose, allowing the determination of the protonation states within the active site. This information was extended by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. The results suggest a new mechanism involving changes in the conformation and protonation state of the catalytic triad, as well as a new role for Tyr27, providing new insights into the hydrolysis and transglycosylation activities. PMID- 26143918 TI - Intercalating dyes for enhanced contrast in second-harmonic generation imaging of protein crystals. AB - The second-harmonic generation (SHG) activity of protein crystals was found to be enhanced by up to ~1000-fold by the intercalation of SHG phores within the crystal lattice. Unlike the intercalation of fluorophores, the SHG phores produced no significant background SHG from solvated dye or from dye intercalated into amorphous aggregates. The polarization-dependent SHG is consistent with the chromophores adopting the symmetry of the crystal lattice. In addition, the degree of enhancement for different symmetries of dyes is consistent with theoretical predictions based on the molecular nonlinear optical response. Kinetics studies indicate that intercalation arises over a timeframe of several minutes in lysozyme, with detectable enhancements within seconds. These results provide a potential means to increase the overall diversity of protein crystals and crystal sizes amenable to characterization by SHG microscopy. PMID- 26143920 TI - Protein-complex structure completion using IPCAS (Iterative Protein Crystal structure Automatic Solution). AB - Protein complexes are essential components in many cellular processes. In this study, a procedure to determine the protein-complex structure from a partial molecular-replacement (MR) solution is demonstrated using a direct-method-aided dual-space iterative phasing and model-building program suite, IPCAS (Iterative Protein Crystal structure Automatic Solution). The IPCAS iteration procedure involves (i) real-space model building and refinement, (ii) direct-method-aided reciprocal-space phase refinement and (iii) phase improvement through density modification. The procedure has been tested with four protein complexes, including two previously unknown structures. It was possible to use IPCAS to build the whole complex structure from one or less than one subunit once the molecular-replacement method was able to give a partial solution. In the most challenging case, IPCAS was able to extend to the full length starting from less than 30% of the complex structure, while conventional model-building procedures were unsuccessful. PMID- 26143919 TI - Structure of protease-cleaved Escherichia coli alpha-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment. AB - Bacterial alpha-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli alpha-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli alpha-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli alpha-2-macroglobulin and human alpha-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group. PMID- 26143921 TI - Controlled crystal dehydration triggers a space-group switch and shapes the tertiary structure of cytomegalovirus immediate-early 1 (IE1) protein. AB - Cytomegalovirus immediate-early 1 (IE1) protein is a key viral effector protein that reprograms host cells. Controlled dehydration experiments with IE1 crystals not only extended their diffraction limit from 2.85 to 2.3 A resolution but also triggered a monoclinic to tetragonal space-group transition with only minor alterations in the unit-cell parameters. An analysis of the pre-dehydration and post-dehydration crystal structures shows how dehydration rearranges the packing of IE1 molecules to meet the unit-cell constraints of the higher lattice symmetry. The transition from P21 to P43 reduces the number of copies in the asymmetric unit from four to two, and molecules previously related by noncrystallographic symmetry merge into identical crystallographic copies in the tetragonal space group. At the same time, dehydration considerably alters the tertiary structure of one of the two remaining IE1 chains in the asymmetric unit. It appears that this conformational switch is required to compensate for a transition that is assumed to be unfavourable, namely from a highly preferred to a rarely observed space group. At the same time, the dehydration-triggered molecular reshaping could reveal an inherent molecular flexibility that possibly informs on the biological function of IE1, namely on its binding to target proteins from the host cell. PMID- 26143923 TI - Structural plasticity in Mycobacterium tuberculosis uracil-DNA glycosylase (MtUng) and its functional implications. AB - 17 independent crystal structures of family I uracil-DNA glycosylase from Mycobacterium tuberculosis (MtUng) and its complexes with uracil and its derivatives, distributed among five distinct crystal forms, have been determined. Thermodynamic parameters of binding in the complexes have been measured using isothermal titration calorimetry. The two-domain protein exhibits open and closed conformations, suggesting that the closure of the domain on DNA binding involves conformational selection. Segmental mobility in the enzyme molecule is confined to a 32-residue stretch which plays a major role in DNA binding. Uracil and its derivatives can bind to the protein in two possible orientations. Only one of them is possible when there is a bulky substituent at the 5' position. The crystal structures of the complexes provide a reasonable rationale for the observed thermodynamic parameters. In addition to providing fresh insights into the structure, plasticity and interactions of the protein molecule, the results of the present investigation provide a platform for structure-based inhibitor design. PMID- 26143922 TI - Structural and biochemical analyses of a Clostridium perfringens sortase D transpeptidase. AB - The assembly and anchorage of various pathogenic proteins on the surface of Gram positive bacteria is mediated by the sortase family of enzymes. These cysteine transpeptidases catalyze a unique sorting signal motif located at the C-terminus of their target substrate and promote the covalent attachment of these proteins onto an amino nucleophile located on another protein or on the bacterial cell wall. Each of the six distinct classes of sortases displays a unique biological role, with sequential activation of multiple sortases often observed in many Gram positive bacteria to decorate their peptidoglycans. Less is known about the members of the class D family of sortases (SrtD), but they have a suggested role in spore formation in an oxygen-limiting environment. Here, the crystal structure of the SrtD enzyme from Clostridium perfringens was determined at 1.99 A resolution. Comparative analysis of the C. perfringens SrtD structure reveals the typical eight-stranded beta-barrel fold observed in all other known sortases, along with the conserved catalytic triad consisting of cysteine, histidine and arginine residues. Biochemical approaches further reveal the specifics of the SrtD catalytic activity in vitro, with a significant preference for the LPQTGS sorting motif. Additionally, the catalytic activity of SrtD is most efficient at 316 K and can be further improved in the presence of magnesium cations. Since C. perfringens spores are heat-resistant and lead to foodborne illnesses, characterization of the spore-promoting sortase SrtD may lead to the development of new antimicrobial agents. PMID- 26143924 TI - Structure of the catalytic phosphatase domain of MTMR8: implications for dimerization, membrane association and reversible oxidation. AB - Myotubularin-related proteins are a large family of phosphoinositide phosphatases; their activity, stability and subcellular localization are regulated by dimeric interactions with other members of the family. Here, the crystal structure of the phosphatase domain of MTMR8 is reported. Conformational deviation of the two loops that mediate interaction with the PH-GRAM domain suggests that the PH-GRAM domain interacts differently with the phosphatase domain of each MTMR member. The protein exists as a dimer with twofold symmetry, providing insight into a novel mode of dimerization mediated by the phosphatase domain. Structural comparison and mutation studies suggest that Lys255 of MTMR8 interacts with the substrate diacylglycerol moiety, similar to Lys333 of MTMR2, although the positions of these residues are different. The catalytic activity of the MTMR8 phosphatase domain is inhibited by oxidation and is reversibly reactivated by reduction, suggesting the presence of an oxidation-protective intermediate other than a disulfide bond owing to the absence of a cysteine within a disulfide-bond distance from Cys338. PMID- 26143925 TI - Enantioselective oxidation of galactitol 1-phosphate by galactitol-1-phosphate 5 dehydrogenase from Escherichia coli. AB - Galactitol-1-phosphate 5-dehydrogenase (GPDH) is a polyol dehydrogenase that belongs to the medium-chain dehydrogenase/reductase (MDR) superfamily. It catalyses the Zn(2+)- and NAD(+)-dependent stereoselective dehydrogenation of L galactitol 1-phosphate to D-tagatose 6-phosphate. Here, three crystal structures of GPDH from Escherichia coli are reported: that of the open state of GPDH with Zn(2+) in the catalytic site and those of the closed state in complex with the polyols Tris and glycerol, respectively. The closed state of GPDH reveals no bound cofactor, which is at variance with the conformational transition of the prototypical mammalian liver alcohol dehydrogenase. The main intersubunit contacting interface within the GPDH homodimer presents a large internal cavity that probably facilitates the relative movement between the subunits. The substrate analogue glycerol bound within the active site partially mimics the catalytically relevant backbone of galactitol 1-phosphate. The glycerol binding mode reveals, for the first time in the polyol dehydrogenases, a pentacoordinated zinc ion in complex with a polyol and also a strong hydrogen bond between the primary hydroxyl group and the conserved Glu144, an interaction originally proposed more than thirty years ago that supports a catalytic role for this acidic residue. PMID- 26143926 TI - The high-resolution crystal structure of phosphatidylinositol 4-kinase IIbeta and the crystal structure of phosphatidylinositol 4-kinase IIalpha containing a nucleoside analogue provide a structural basis for isoform-specific inhibitor design. AB - Phosphatidylinositol 4-phosphate (PI4P) is the most abundant monophosphoinositide in eukaryotic cells. Humans have four phosphatidylinositol 4-kinases (PI4Ks) that synthesize PI4P, among which are PI4K IIbeta and PI4K IIalpha. In this study, two crystal structures are presented: the structure of human PI4K IIbeta and the structure of PI4K IIalpha containing a nucleoside analogue. The former, a complex with ATP, is the first high-resolution (1.9 A) structure of a PI4K. These structures reveal new details such as high conformational heterogeneity of the lateral hydrophobic pocket of the C-lobe and together provide a structural basis for isoform-specific inhibitor design. PMID- 26143927 TI - From bacterial to human dihydrouridine synthase: automated structure determination. AB - The reduction of uridine to dihydrouridine at specific positions in tRNA is catalysed by dihydrouridine synthase (Dus) enzymes. Increased expression of human dihydrouridine synthase 2 (hDus2) has been linked to pulmonary carcinogenesis, while its knockdown decreased cancer cell line viability, suggesting that it may serve as a valuable target for therapeutic intervention. Here, the X-ray crystal structure of a construct of hDus2 encompassing the catalytic and tRNA-recognition domains (residues 1-340) determined at 1.9 A resolution is presented. It is shown that the structure can be determined automatically by phenix.mr_rosetta starting from a bacterial Dus enzyme with only 18% sequence identity and a significantly divergent structure. The overall fold of the human Dus2 is similar to that of bacterial enzymes, but has a larger recognition domain and a unique three stranded antiparallel beta-sheet insertion into the catalytic domain that packs next to the recognition domain, contributing to domain-domain interactions. The structure may inform the development of novel therapeutic approaches in the fight against lung cancer. PMID- 26143928 TI - High-resolution crystal structures of the solubilized domain of porcine cytochrome b5. AB - Mammalian microsomal cytochrome b5 has multiple electron-transfer partners that function in various electron-transfer reactions. Four crystal structures of the solubilized haem-binding domain of cytochrome b5 from porcine liver were determined at sub-angstrom resolution (0.76-0.95 A) in two crystal forms for both the oxidized and reduced states. The high-resolution structures clearly displayed the electron density of H atoms in some amino-acid residues. Unrestrained refinement of bond lengths revealed that the protonation states of the haem propionate group may be involved in regulation of the haem redox properties. The haem Fe coordination geometry did not show significant differences between the oxidized and reduced structures. However, structural differences between the oxidized and reduced states were observed in the hydrogen-bond network around the axial ligand His68. The hydrogen-bond network could be involved in regulating the redox states of the haem group. PMID- 26143929 TI - High fructose consumption in pregnancy alters the perinatal environment without increasing metabolic disease in the offspring. AB - Maternal carbohydrate intake is one important determinant of fetal body composition, but whether increased exposure to individual sugars has long-term adverse effects on the offspring is not well established. Therefore, we examined the effect of fructose feeding on the mother, placenta, fetus and her offspring up to 6 months of life when they had been weaned onto a standard rodent diet and not exposed to additional fructose. Dams fed fructose were fatter, had raised plasma insulin and triglycerides from mid-gestation and higher glucose near term. Maternal resistance arteries showed changes in function that could negatively affect regulation of blood pressure and tissue perfusion in the mother and development of the fetus. Fructose feeding had no effect on placental weight or fetal metabolic profiles, but placental gene expression for the glucose transporter GLUT1 was reduced, whereas the abundance of sodium-dependent neutral amino acid transporter-2 was raised. Offspring born to fructose-fed and control dams were similar at birth and had similar post-weaning growth rates, and neither fat mass nor metabolic profiles were affected. In conclusion, raised fructose consumption during reproduction results in pronounced maternal metabolic and vascular effects, but no major detrimental metabolic effects were observed in offspring up to 6 months of age. PMID- 26143930 TI - Insights from Chromosome-Centric Mapping of Disease-Associated Genes: Chromosome 12 Perspective. AB - In line with the aims of the Chromosome-based Human Proteome Project and the Biology/Disease-based Human Proteome Project, we have been studying differentially expressed transcripts and proteins in gliomas-the most prevalent primary brain tumors. Here, we present a perspective on important insights from this analysis in terms of their co-expression, co-regulation/de-regulation, and co-localization on chromosome 12 (Chr. 12). We observe the following: (1) Over expression of genes mapping onto amplicon regions of chromosomes may be considered as a biological validation of mass spectrometry data. (2) Their co localization further suggests common determinants of co-expression and co regulation of these clusters. (3) Co-localization of "missing" protein genes of Chr. 12 in close proximity to functionally related genes may help in predicting their functions. (4) Further, integrating differentially expressed gene-protein sets and their ontologies with medical terms associated with clinical phenotypes in a chromosome-centric manner reveals a network of genes, diseases, and pathways a diseasome network. Thus, chromosomal mapping of disease data sets can help uncover important regulatory and functional links that may offer new insights for biomarker development. PMID- 26143931 TI - Antioxidant and Anti-Inflammatory Phenolic Glycosides from Clematis tashiroi. AB - From the 95% EtOH extract of dried aerial parts of Clematis tashiroi, eight new and four known phenolic (caffeic acid, coumaric acid, ferrulic acid) glycosides were isolated and characterized. The structures of the new isolates (clematisides A-H) were elucidated by spectroscopic data interpretation as trans-4-O-(6-O-trans caffeoyl-beta-D- glucopyranosyl)-9-O-beta-D-glucopyranosyl caffeic acid (1), trans-4-O-(6-O-trans-feruloyl-beta-D-glucopyranosyll)-9-O-beta-D-glucopyranosyl caffeic acid (2), trans-4-O-(6-O-trans-p-coumaroyl-beta-D-glucopyranosyl)-9-O beta-D-glucopyranosyl caffeic acid (3), trans-4-O-(6-O-trans-caffeoyl-beta-D glucopyranosyl)-9-O-beta-D-glucopyranosyl p-coumaric acid (4), trans-3-O-(6-O trans-caffeoyl-beta-D-glucopyranosyl)-9-O-beta-D-glucopyranosyl caffeic acid (5), trans-3-O-(6-O-trans-p-coumaroyl-beta-D-glucopyranosyl)-9-O-beta-D-glucopyranosyl caffeic acid (6), 6-(3',4'-dihydroxystyryl)-2-pyrone-4-O-(6-O-trans-caffeoyl) beta-D-glucopyranoside (7), and 6-(3',4'-dihydroxystyryl)-2-pyrone-4-O-{6-O-[4-O (6-O-trans-caffeoyl)-beta-D-glucopyranosyl]-trans-caffeoyl}-beta-D glucopyranoside (8), respectively. In a DPPH radical-scavenging test, compounds 1, 7, and 8 showed more potent antioxidant activity than that of the positive control, vitamin E. In addition, compound 7 also showed inhibitory activity in an antinitric oxide release assay. PMID- 26143932 TI - In Situ Formation of ZnO in Graphene: A Facile Way To Produce a Smooth and Highly Conductive Electron Transport Layer for Polymer Solar Cells. AB - A novel electron transport layer (ETL) based on zinc oxide@graphene:ethyl cellulose (ZnO@G:EC) nanocomposite is prepared by in situ formation of zinc oxide (ZnO) nanocrystals in a graphene matrix to improve the performance of polymer solar cells. Liquid ultrasound exfoliation by ethyl cellulose as stabilizer not only allows for uniform dispersion of graphene solution but also maintains an original structure of graphene gaining a high conductivity. The ZnO@G:EC ETL displays a quite smooth morphology and develops the energy-level alignment for the electron extraction and transportation. Subsequently, the device based on poly(3-hexylthiophene) (P3HT):(6,6)-phenyl-C61 butyric acid methyl ester (PC61BM) with the ZnO@G:EC as ETL obtains a power conversion efficiency (PCE) of 3.9%, exhibiting a ~20% improvement compared to the familiar device with bare ZnO nanocrystals as ETL. Replacing the active layer with polythieno[3,4 b]thiophene/benzodithiophene (PTB7): (6,6)-phenyl-C71 butyric acid methyl ester (PC71BM), the PCE can be dramatically improved to 8.4%. This facile and fascinating method to produce a smooth and highly conductive electron transport layer provides an anticipated approach to obtain high performance polymer solar cells. PMID- 26143933 TI - A comparison of human metapneumovirus and respiratory syncytial virus WHO-defined severe pneumonia in Moroccan children. AB - Acute respiratory infections remain the principal cause of morbidity and mortality in Moroccan children. Besides bacterial infections, respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are prominent among other viruses due to their high prevalence and association with severe clinical episodes. We aimed to describe and compare RSV- and hMPV-associated cases of WHO defined severe pneumonia in a paediatric population admitted to Morocco's reference hospital. Children aged 2-59 months admitted to the Hopital d'Enfants de Rabat, Morocco meeting WHO-defined severe pneumonia criteria were recruited during 14 months and thoroughly investigated to ascertain a definitive diagnosis. Viral prevalence of RSV, hMPV and other viruses causing respiratory symptoms was investigated in nasopharyngeal aspirate samples through the use of molecular methods. Of the 683 children recruited and included in the final analysis, 61/683 (8.9%) and 124/683 (18.2%) were infected with hMPV and RSV, respectively. Besides a borderline significant tendency for higher age in hMPV cases, patients infected with either of the viruses behaved similarly in terms of demographics, patient history, past morbidity and comorbidity, vaccination history, socioeconomic background and family environment. Clinical presentation on arrival was also similar for both viruses, but hMPV cases were associated with more severity than RSV cases, had a higher risk of intensive care need, and received antibiotic treatment more frequently. RSV and hMPV are common and potentially life threatening causes of WHO-defined pneumonia in Moroccan children. Both viruses show indistinctive clinical symptomatology, but in Moroccan children, hMPV was associated with a more severe evolution. PMID- 26143934 TI - Field Switching Combined with Bradbury-Nielsen Gate for Ion Mobility Spectrometry. AB - Bradbury-Nielsen gate (BNG) is commonly used in ion mobility spectrometers. It, however, transmits only a small fraction of the ions into the drift region, typically 1%. In contrast, all ions in the ionization chamber could be efficiently compressed into the drift region by the field switching gate (FSG). We report in this paper on the simultaneous use of BNG and field switching (FS) to enhance ion utilization of the BNG. In this technique, the FS collects the ions existing in the region between the FS electrode and the BNG and drives them quickly, going through the BNG in the period of gate opening. The BNG acts as the retarding field in the reported FSG to stop ions from diffusing into the drift region in the period of gate closing. Using this technique, an increase of at least 10-fold in the ion peak height without any loss of resolution is achieved for acetone compared with the BNG-only approach at a gate pulse width of 150 MUs, and an even larger improvement factor of 21 is achieved for heavier DMMP dimer ions. This technique can be adapted to the current BNG-based ion mobility instruments to significantly enhance their sensitivity without any modification of the drift tube hardware. PMID- 26143935 TI - Effect of systemic clarithromycin and prednisolone on histamine-induced otitis media in guinea pigs. AB - CONCLUSION: The results of the study showed that clarithromycin has anti inflammatory and antioxidant effects and, when it is combined with prednisolone, those effects gain strength. OBJECTIVES: The present study aims to investigate the effects that the antioxidant and anti-inflammatory activities of clarithromycin and/or prednisolone have on experimental otitis media in effusion induced guinea-pigs. METHOD AND RESULTS: In this study, 35-male guinea pigs were randomly divided into five-groups. For the experimental otitis media, intra tympanic histamine (0.1 ml) was injected into the guinea pigs in all of the groups except the control group. Then, 24-h after the intra-tympanic injections, clarithromycin (15 mg/kg/day) and/or prednisolone (1 mg/kg/day) were applied intraperitoneally to the guinea-pigs for 7-days. The biochemical analysis showed an increase in antioxidant capacity and a decrease in oxidant status and malondialdehyde (MDA) levels in the clarithromycin group and the prednisolone group and especially in the clarithromycin+prednisolone group, as compared to the experimental group (p < 0.05). In the cytokine analysis, lower levels of interleukin (IL)-6 and IL-17A and higher IL-10 were found in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups than in the experimental group (p < 0.05). Furthermore, the histologic analyses showed histopathologic changes in the middle ear mucosa of the experimental group, but comparatively fewer-histopathologic changes were observed in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups. PMID- 26143936 TI - Focusing the mechanism of action to dissect the different treatments of respiratory allergy. AB - The treatment of respiratory allergy is based on several drugs with different mechanisms of action, which encompass an effect only on symptoms, limited factors of inflammation or the whole process of inflammation. Dissecting the different treatments by their mechanism of action is relevant for the management of allergic patients. Corticosteroids, administered as nasal sprays in rhinitis or by inhalation devices in asthma, and allergen immunotherapy (AIT) are the most effective treatments for respiratory allergy, achieving the control on inflammation by a number of cellular and molecular mechanisms. What distinguishes corticosteroids from AIT is the duration of clinical outcomes that ends with treatment withdrawal for the former but persists after stopping for AIT, due to its disease-modifying effect. PMID- 26143937 TI - Quantitation of viable Coxiella burnetii in milk using an integrated cell culture polymerase chain reaction (ICC-PCR) assay. AB - The obligate intracellular pathogen Coxiella burnetii has long been considered the most heat resistant pathogen in raw milk, making it the reference pathogen for determining pasteurisation conditions for milk products. New milk formulations and novel non-thermal processes require validation of effectiveness which requires a more practical method for analysis than using the currently used animal model for assessing Coxiella survival. Also, there is an interest in better characterising thermal inactivation of Coxiella in various milk formulations. To avoid the use of the guinea pig model for evaluating Coxiella survival, an Integrated Cell Culture-PCR (ICC-PCR) method was developed for determining Coxiella viability in milk. Vero cell cultures were directly infected from Coxiella-contaminated milk in duplicate 24-well plates. Viability of the Coxiella in milk was shown by a >= 0.5 log genome equivalent (ge)/ml increase in the quantity of IS111a gene from the baseline post-infection (day 0) level after 9-11 d propagation. Coxiella in skim, 2%, and whole milk, and half and half successfully infected Vero cells and increased in number by at least 2 logs using a 48-h infection period followed by 9-d propagation time. As few as 125 Coxiella ge/ml in whole milk was shown to infect and propagate at least 2 logs in the optimised ICC-PCR assay, though variable confirmation of propagation was shown for as low as 25 Coxiella ge/ml. Applicability of the ICC-PCR method was further proven in an MPN format to quantitate the number of viable Coxiella remaining in whole milk after 60 degrees C thermal treatment at 0, 20, 40, 60 and 90 min. PMID- 26143938 TI - Executive functioning profiles from the BRIEF across pediatric medical disorders: Age and diagnosis factors. AB - The objective of the study was to compare executive functioning (EF) profiles across several pediatric medical conditions and explore the influence of age of diagnosis and evaluation. A retrospective, cross-sectional study of 734 children aged 5 to 18 years was conducted across five medical groups (brain tumor, leukemia [ALL], epilepsy [EPI], neurofibromatosis type 1 [NF1], and ornithine transcarbamylase deficiency [OTC-D]), attention deficit hyperactivity disorder (ADHD) controls, and matched healthy controls. We compared groups across the scales of a parent-completed Behavior Rating Inventory of Executive Functioning (BRIEF) using a repeated measures analysis of variance (ANOVA). Separate ANOVAs were conducted to look at age factors. The results showed that the ADHD group differed from all other groups and had the highest level of reported EF problems. The NF1 and OTC-D groups differed significantly from the healthy comparison group for overall EF problems, while the EPI and cancer groups did not. Working memory was the most elevated scale across medical groups, followed by plan/organize. Children with medical disorders were two to four times more likely than healthy controls to have clinically significant problems in several EF domains. There was a main effect for age at diagnosis and age at evaluation. A subset of children with medical disorders were found to have parent-reported EF difficulties, with particular vulnerability noted in working memory and organizational/planning skills. This has relevance for the development of interventions that may be helpful across disorders. Children with particular diagnoses and earlier age of diagnosis and evaluation had greater reported EF problems. PMID- 26143940 TI - Engineering Optical and Electronic Properties of WS2 by Varying the Number of Layers. AB - The optical constants, bandgaps, and band alignments of mono-, bi-, and trilayer WS2 were experimentally measured, and an extraordinarily high dependency on the number of layers was revealed. The refractive indices and extinction coefficients were extracted from the optical-contrast oscillation for various thicknesses of SiO2 on a Si substrate. The bandgaps of the few-layer WS2 were both optically and electrically measured, indicating high exciton-binding energies. The Schottky barrier heights (SBHs) with Au/Cr contact were also extracted, depending on the number of layers (1-28). From an engineering viewpoint, the bandgap can be modulated from 3.49 to 2.71 eV with additional layers. The SBH can also be reduced from 0.37 eV for a monolayer to 0.17 eV for 28 layers. The technique of engineering materials' properties by modulating the number of layers opens pathways uniquely adaptable to transition-metal dichalcogenides. PMID- 26143939 TI - A novel measurement method for the morphology of the mandibular ramus using homologous modelling. AB - OBJECTIVES: It is important to assess the mandibular morphology when orthognathic surgery, especially mandibular ramus osteotomy, is performed. Several studies on three-dimensional (3D) facial asymmetry have reported differences in linear and angle measurements between the deviated and contralateral sides in asymmetric mandibles. However, methods used in these studies cannot analyse the 3D morphology of the ramus. In this study, we aimed to evaluate the differences in mandibular ramus between the deviated and contralateral sides in asymmetric mandibles using traditional measurements as well as 3D shape analysis. METHODS: 15 Japanese females with jaw deformities treated by orthodontic surgery were enrolled. 3D CT images were reconstructed, and 14 landmarks were identified on the model surface. Ten linear and four angle measurements were calculated using these landmarks. Homologous ramus models were constructed for each sample, and after converting all homologous models to the right side, 30 homologous models of the ramus were analysed using principal component analysis. RESULTS: Firstly, eight principal components explained >80% of the total variance. Differences between the deviated and contralateral sides in measurements and scores of the eight principal components were tested. Significant difference at the 5% level between the deviated and contralateral sides was observed in five linear measurements, three angle measurements and the third principal component. The variance of the deviated side was significantly larger in the diameter between the mandibular notch and coronoid process, horizontal dilated angle of the mandibular ramus and vertical dilated angle of the mandibular ramus. The variance of the contralateral side was significantly larger in the height of mandibular ramus, height of posterior of mandibular ramus, condylar width, height of condylar head and mandibular angle. The squared multiple correlation coefficient adjusted for the degrees of freedom was 0.815. The third principal component showed the difference between the deviated and contralateral sides. Shape variation represented by the third principal component visually indicated that the contralateral side was larger and had inwardly directed coronoid process and the deviated side had a mandibular angle that was turned inwards to a greater extent. CONCLUSIONS: In conclusion, we successfully created a homologous model of the mandibular ramus and demonstrated the effectiveness of this model in the 3D comparison of the ramus morphology between the contralateral and deviated sides in asymmetric mandibles. PMID- 26143941 TI - Rare case of urinary tract infections and the "forgotten" solution. AB - This report presents a rare case of recurrent urinary tract infections in a kidney transplant patient. Analysis revealed a ureteral stump calculus 31 years after bilateral nephrectomy which was disintegrated by means of flexible ureteroscopy and holmium laser. In case of unexplained recurrent urinary tract infections and abdominal pain, urolithiasis in the ureteral stumps should be considered. PMID- 26143942 TI - Lorazepam v. diazepam for pediatric status epilepticus. AB - Clinical question Is intravenous (IV) lorazepam superior to IV diazepam in the treatment of pediatric status epilepticus? Article chosen Chamberlain JM, Okada P, Holsti M, et al. Lorazepam v. diazepam for pediatric status epilepticus: a randomized clinical trial. JAMA 2014;311(16):1652-60. OBJECTIVE: To determine whether lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus. PMID- 26143943 TI - Therapeutic contact lenses: a patent review. AB - INTRODUCTION: Ophthalmic drugs are almost exclusively delivered via eye drops in spite of several deficiencies, including low bioavailability and poor compliance. Contact lenses have the potential to increase bioavailability by an order of magnitude, while also improving compliance. AREAS COVERED: In this review, the authors summarize advances in therapeutic contact lenses. The major focus of the review is on patents on drug-eluting contact lenses, but non-drug-eluting contacts that offer a therapeutic benefit are also included. The content is divided based on the broad technology of the patent, including novel materials, molecular imprinting, diffusion barriers, colloid encapsulation, surface modification, layering, and other novel approaches. In addition to patents, research publications are also included to facilitate the understanding of the mechanisms and challenges. EXPERT OPINION: Among all non-invasive alternatives, contact lenses offer the highest bioavailability to the cornea due to the location of the lens in the immediate vicinity of the cornea. Several approaches have been patented to improve contact lens design for an extended release duration of drugs. Many technologies have successfully integrated suitable drug release profiles into contact lenses, but drug-eluting contacts are not yet commercialized likely due to regulatory challenges, including the high costs of clinical trials. PMID- 26143944 TI - In Silico Designing and Screening of Antagonists against Cancer Drug Target XIAP. AB - X-linked inhibitor of apoptosis (XIAP) is a member of inhibitor of apoptosis (IAP) family and involved in the suppression of apoptosis in cancer cells. This property makes it a therapeutic target for the cancer therapy. In the present study, we have developed QSAR models using chemical descriptors, fingerprints, principal components, docking energy parameters and similarity-based approach against XIAP. We have achieved correlation (R) of 0.803 with R(2) value of 0.645 at 10-fold cross validation using SMOreg algorithm. We have evaluated these models on independent dataset to ascertain its robustness and achieved correlation (R) of 0.793 with R(2) value of 0.628. Further, we have used these models for the screening of FDA approved drugs and drug-like molecules from ZINC database and prioritized them on the basis of their predicted pIC50 values. Docking studies of top hits with XIAP-BIR3 domain shows that Iodixanol (DB01249) and ZINC68678304 have higher binding affinities than well-known tetrapeptide inhibitor, AVPI. We have integrated these models in a web server named as "XIAPin". We hope that this web server will contribute in the designing of nifty antagonists against XIAP. PMID- 26143945 TI - AKT and cytosolic phospholipase A2alpha form a positive loop in prostate cancer cells. AB - Aberrant increase in protein kinase B (AKT) phosphorylation (pAKT), due to a gain of-function mutation of phosphatidylinositol-3-kinase (PI3K) or loss-of-function mutation or deletion of phosphatase and tensin homolog (PTEN), is a common alteration in prostate cancer and associated with poor prognosis. Cytosolic phospholipase A2alpha (cPLA2alpha) is a lipid modifying enzyme by catalyzing the hydrolysis of arachidonic acid from membrane phospholipid. The released arachidonic acid and its metabolites contribute to survival and proliferation of prostate cancer cells. In this mini-review, we summarize the relationship between pAKT and cPLA2alpha in prostate cancer cells. There was a concordant increase in pAKT and cPLA2alpha levels in prostate tissue of prostate epithelial-specific PTEN-knockout mice compared to PTEN-wild type mice. Restoration of PTEN expression or inhibition of PI3K action decreased cPLA2alpha expression in PTEN mutated or deleted prostate cancer cells. An increase in AKT phosphorylation elevated, whereas inhibition of AKT phosphorylation diminished, cPLA2alpha protein levels. pAKT had no influence on cPLA2alpha expression at mRNA levels but stabilized cPLA2alpha at protein levels by protecting it from degradation. Conversely, an induction of cPLA2alpha expression led to an increase in pAKT levels in PTEN-mutated or deleted prostate cancer cells, while silencing of cPLA2alpha expression or pharmacological blocking cPLA2alpha action decreased pAKT levels. The diminishment of pAKT by either genetic silencing or pharmacological blocking of cPLA2alpha was mitigated by the addition of arachidonic acid. The stimulatory effect of arachidonic acid on pAKT levels was lessened by inhibiting the production of arachidonic acid metabolites. These studies have revealed a link between oncogenic pathway and lipid metabolism and provided potential molecular targets for treating prostate cancer. PMID- 26143946 TI - Nanobiotechnological Approaches to Overcome Drug Resistance in Breast Cancer. AB - Drug resistance primarily appears where there is altered drug metabolism or target modification. It is a major challenge in cancer therapy which affects treatment process, and limits chemotherapeutics. Recently, nanotechnological approaches were shown to be capable of lowering drug side effects and protecting from enzymatic degradation. Therefore, patient's compliance and survival rate have dramatically increased. This review elaborates on the structures and functions of the factors involved in cancer drug resistance together with nanobiotechnological approaches for overcoming the obstacles in breast cancer research and therapy. The present paper provides information and suggestions to both basic and clinical researchers to develop new nanobiotechnological methods to improve breast cancer modalities especially in drug resistance. PMID- 26143947 TI - [Knowledge of health outcomes generated by drugs in the real world: Temporary fashion or real need?]. PMID- 26143948 TI - [Different evolution of atrial fibrillation after the first documented episode]. PMID- 26143949 TI - [Anti-synthetase syndrome. Mechanic's hands]. PMID- 26143950 TI - Optogenetic neuromodulation: new tools for monitoring and breaking neural circuits. AB - Optogenetics is the combination of optical tools to monitor (i.e. "reporters") or interfere (i.e. "actuators") with neural activity, and genetic techniques to restrain the expression of these reporters and actuators in the neuronal populations of interest. Such combination of optical and genetic tools, together with the emergence of new animal models such as the zebrafish larva, has proven extremely valuable is dissecting neural circuits. Optogenetics provide a new framework to address issues that are fundamentally dynamic processes, such as sensorimotor integration in the vertebrate spinal cord. By shifting from spatially targeted electrical stimulation to genetically targeted optical stimulation, optogenetic also opens new avenues for innovative neurorehabilitative strategies, in particular after spinal cord injury. PMID- 26143951 TI - Waterpipe Use and Susceptibility to Cigarette Smoking Among Never-Smoking Youth. AB - INTRODUCTION: Susceptibility to cigarette smoking, defined as the lack of a firm decision against smoking, is a strong predictor of regular smoking and addiction. Several modifiable risk factors have been identified among never cigarette smokers, and one potential factor of interest is waterpipe use. The purpose of this study is to determine the association of waterpipe use with susceptibility to cigarette smoking among never-smoking youth. METHODS: In a pooled analysis of 17 Arab nations with nationally representative Global Youth Tobacco Surveys conducted during 2002-2011, tobacco-related information was obtained from 30,711 never-smoking adolescents representing 4,962,872 youth. Study outcome was susceptibility to cigarette smoking, and primary exposure was waterpipe use. Data were analyzed in 2014 using weighted logistic regression models, including stratified models by gender, to determine the odds of susceptibility to cigarette smoking with waterpipe use, adjusting for confounders. RESULTS: Overall, 20% of never-smoking youth were susceptible to cigarette smoking, ranging from 13.1% in Oman to 32.6% in Somalia; 5.2% currently used waterpipe, ranging from 0.3% in Morocco to 23.5% in Kuwait. The estimated odds of susceptibility to cigarette smoking were 2.5 (95% CI=1.9, 3.4) times higher for adolescents who used waterpipe in the past month compared with those who did not, controlling for confounders. Estimates were similar when stratified by gender. CONCLUSIONS: Waterpipe use is associated with susceptibility to cigarette smoking. Study findings identify a novel risk factor for never smokers to initiate smoking and will help the public health community develop and implement policies around waterpipe use prevention. PMID- 26143952 TI - Preferences for Mental Health Screening Among Pregnant Women: A Cross-Sectional Study. AB - INTRODUCTION: The process of mental health screening can influence disclosure, uptake of referral, and treatment; however, no studies have explored pregnant women's views of methods of mental health screening. The objectives of this study are to determine pregnant women's comfort and preferences regarding mental health screening. METHODS: Pregnant women were recruited (May-December 2013) for this cross-sectional descriptive survey from prenatal classes and maternity clinics in Alberta, Canada, if they were aged >16 years and spoke/read English. Descriptive statistics summarized acceptability of screening, and multivariable logistic regression identified factors associated with women's comfort with screening methods. Analysis was conducted in January-December 2014. RESULTS: The participation rate was 92% (N=460/500). Overall, 97.6% of women reported that they were very (74.8%) or somewhat (22.8%) comfortable with mental health screening in pregnancy. Women were most comfortable with completing paper- (>90%) and computer-based (>82%) screening in a clinic or at home, with fewest reporting comfort with telephone-based screening (62%). The majority of women were very/somewhat comfortable with provider-initiated (97.4%) versus self-initiated (68.7%) approaches. Women's ability to be honest with their provider about emotional health was most strongly associated with comfort with each method of screening. CONCLUSIONS: The majority of pregnant women viewed prenatal mental health screening favorably and were comfortable with a variety of screening methods. These findings provide evidence of high acceptability of screening--a key criterion for implementation of universal screening--and suggest that providers can select from a variety of screening methods best suited for their clinical setting. PMID- 26143953 TI - Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines. AB - INTRODUCTION: Opioid analgesics and benzodiazepines are the prescription drugs most commonly associated with drug overdose deaths. This study was conducted to assess trends in nonmedical use-related emergency department (ED) visits and drug overdose deaths that involved both opioid analgesics and benzodiazepines in the U.S. from 2004 to 2011. METHODS: Opioid analgesic and benzodiazepine nonmedical use-related ED visits from the Drug Abuse Warning Network and drug overdose deaths from the National Vital Statistics System were analyzed for 2004-2011 to determine trends and demographic-specific rates. Data were analyzed from March 2014 to June 2014. RESULTS: From 2004 to 2011, the rate of nonmedical use-related ED visits involving both opioid analgesics and benzodiazepines increased from 11.0 to 34.2 per 100,000 population (p-trend<0.0001). During the same period, drug overdose deaths involving both drugs increased from 0.6 to 1.7 per 100,000 (p-trend<0.0001). Statistically significant increases in ED visits occurred among males and females, non-Hispanic whites, non-Hispanic blacks, and Hispanics, and all age groups except 12- to 17-year-olds. For overdose deaths, statistically significant increases were seen in males and females, all three race/ethnicity groups, and all age groups except 12- to 17-year-olds. Benzodiazepine involvement in opioid analgesic overdose deaths increased each year, increasing from 18% of opioid analgesic overdose deaths in 2004 to 31% in 2011 (p-trend<0.0001). CONCLUSIONS: ED visits and drug overdose deaths involving both opioid analgesics and benzodiazepines increased significantly between 2004 and 2011. Interventions to improve the appropriate prescribing and use of these medications are needed. PMID- 26143954 TI - Support for Physical Education as a Core Subject in Urban Elementary Schools. AB - INTRODUCTION: Physical inactivity and childhood obesity are prevalent in American children, with increased vulnerability in minority, low-resource populations. The aim of this study was to quantify the impact of physical education (PE) on in school physical activity quantity and intensity in urban minority children attending public elementary schools. METHODS: This observational study included elementary children (N=212; mean age, 9.9 years; 81.7% black) in Grades 2-5 attending urban public schools with high eligibility for the National School Lunch Program. In-school physical activity was quantified during 4 school weeks across 4 months (January-April 2012) using Omron HJ-151 accelerometer-pedometers. Fitness was assessed with the 20-meter Progressive Aerobic Cardiovascular Endurance Run. Data were analyzed in 2013 using generalized estimating equations to determine the influence of PE and sex on total in-school steps and moderate to vigorous physical activity (MVPA) steps. RESULTS: Based on 3,379 observation days (mean, 15.9 school days/student), students achieved higher in-school physical activity on days with PE (4,979 steps) than on days without PE (3,683 steps, p<0.0001). Likewise, MVPA steps were greater on days with PE than on days without PE (p<0.0001). Boys were more active than girls, but both accumulated more steps on days with PE. Low aerobic fitness was observed in 29.0% of students and overweight/obesity in 31.1%. CONCLUSIONS: PE significantly increases total in school and MVPA steps in urban minority elementary children. PE as a core subject can provide opportunities for urban, minority public school children in low resource areas to achieve age-appropriate physical activity and fitness goals. PMID- 26143955 TI - Disparities in Cancer Incidence, Stage, and Mortality at Boston Health Care for the Homeless Program. AB - INTRODUCTION: Homeless people have a high burden of cancer risk factors and suboptimal rates of cancer screening, but the epidemiology of cancer has not been well described in this population. We assessed cancer incidence, stage, and mortality in homeless adults relative to general population standards. METHODS: We cross-linked a cohort of 28,033 adults seen at Boston Health Care for the Homeless Program in 2003-2008 to Massachusetts cancer registry and vital registry records. We calculated age-standardized cancer incidence and mortality ratios (SIRs and SMRs). We examined tobacco use among incident cases and estimated smoking-attributable fractions. Trend tests were used to compare cancer stage distributions with those in Massachusetts adults. Analyses were conducted in 2012 2015. RESULTS: During 90,450 person-years of observation, there were 361 incident cancers (SIR=1.13, 95% CI=1.02, 1.25) and 168 cancer deaths (SMR=1.88, 95% CI=1.61, 2.19) among men, and 98 incident cancers (SIR=0.93, 95% CI=0.76, 1.14) and 38 cancer deaths (SMR=1.61, 95% CI=1.14, 2.20) among women. For both sexes, bronchus and lung cancer was the leading type of incident cancer and cancer death, exceeding Massachusetts estimates more than twofold. Oropharyngeal and liver cancer cases and deaths occurred in excess among men, whereas cervical cancer cases and deaths occurred in excess among women. About one third of incident cancers were smoking-attributable. Colorectal, female breast, and oropharyngeal cancers were diagnosed at more-advanced stages than in Massachusetts adults. CONCLUSIONS: Efforts to reduce cancer disparities in homeless people should include addressing tobacco use and enhancing participation in evidence-based screening. PMID- 26143956 TI - Etiology, clinical course and response to the treatment of status epilepticus in children: A 16-year single-center experience based on 602 episodes of status epilepticus. AB - OBJECTIVE: evaluation of etiology, clinical course and response to the treatment of status epilepticus (SE) in children, with particular investigation of superrefractory SE. MATERIALS AND METHODS: The retrospective study included children with convulsive SE aged 0.2-18 years, treated from 1995 to 2011. Status epilepticus is defined as a continuous seizure or intermittent seizures without full recovery of consciousness between seizures for at least 30 min. Refractory SE is diagnosed if SE lasts for more than 60 min, while superrefractory SE if SE continues or recurs 24 h or more after the onset of an anesthesia therapy, including those cases that recur after reduction or withdrawal of an anesthesia. The etiology was summarized in five categories: idiopathic/cryptogenic, remote symptomatic, febrile SE, acute symptomatic and progressive encephalopathy. The patients were treated according to the same hospital protocol. Midazolam iv and diazepam rectally were given as the first line drugs, phenobarbital/phenytoin iv as the second line drugs. If they failed, third line drugs, midazolam and thiopental were given in continuous intravenous infusion. The medication was defined as effective if seizure clinically stopped within 20 min, without recurrence within the next 6 h. Midazolam was assessed as effective even if it failed as the first line, but was effective in intravenous infusion as the third line drug. RESULTS: The study consisted of 602 SE in 395 children. There were 305 (50.7%) refractory SE episodes, and 43 (7.1%) of superrefractory SE. Idiopathic/cryptogenic and febrile SE was the most common etiology in the first SE, while progressive encephalopathy and remote symptomatic was in recurrent and superrefractory SE. The most effective drugs were: midazolam (306/339) given in mean dose of 0.4 mg/kg (range 0.1-1.2 mg/kg), thiopental (47/57) in mean dose of 4 mg/kg (range 3-5 mg/kg), phenobarbital (91/135) in dose of 20 mg/kg. Midazolam successfully stopped 306/339 SE episodes (90.3%), 67 SE (21.9%) by equal or lower dose than 0.2 mg/kg as the first line drug, while all other 239 episodes (78.9%) were stopped by intravenous infusion in range 0.2-1.2 mg/kg/h (mean 0.4 mg/kg/h) as the third line drug. Adverse effects were frequent in superrefractory SE (60.5%). In 15 patients, corticosteroids contributed to the reduction of seizure recurrence after anesthetic withdrawal and cessation of epilepsia partialis continua. Case fatality rate was 5.1% in all patients, while 21.3% in patients with superrefractory SE. CONCLUSION: Status epilepticus in children was characterized by heterogeneous etiology, prolonged duration and commonly good response to midazolam only given in high doses. Superrefractory SE was not so rare in children, especially among the patients with progressive encephalopathy. PMID- 26143957 TI - Natural Th17 cells are critically regulated by functional medullary thymic microenvironments. AB - The thymic medulla is critical for the enforcement of central tolerance. In addition to deletion of auto-reactive T-cells, the thymic medulla supports the maturation of heterogeneous natural alphabetaT-cells linked to tolerance mechanisms. Natural IL-17-secreting CD4(+)alphabetaT-cells (nTh17) represent recently described natural alphabetaT-cells that mature and undergo functional priming intrathymically. Despite a proposed potential to impact upon either protective or pathological inflammatory responses, the intrathymic mechanisms regulating the balance of nTh17 development are unclear. Here we compare the development of distinct natural alphabetaT-cells in the thymus. We reveal that thymic stromal MHC class II expression and RelB-dependent medullary thymic epithelial cells (mTEC), including Aire(+) mTEC, are an essential requirement for nTh17 development. nTh17 demonstrate a partial, non-redundant requirement for both ICOS-ligand and CD80/86 costimulation, with a dispensable role for CD80/86 expression by thymic epithelial cells. Although mTEC constitutively expressed inducible nitric oxide synthase (iNOS), a critical negative regulator of conventional Th17 differentiation, iNOS was not essential to constrain thymic nTh17. These findings highlight the critical role of the thymic medulla in the differential regulation of novel natural alphabetaT-cell subsets, and reveal additional layers of thymic medullary regulation of T-cell driven autoimmunity and inflammation. PMID- 26143958 TI - Chronic graft-versus-host-disease in CD34(+)-humanized NSG mice is associated with human susceptibility HLA haplotypes for autoimmune disease. AB - Chronic graft-versus-host disease (cGVHD) is a significant hurdle to long-term hematopoietic stem-cell transplantation success. Insights into the pathogenesis and mechanistical investigations of novel therapeutic strategies are limited as appropriate animal models are missing. The immunodeficient NSG mouse - when humanized with human bone marrow, fetal liver and thymus (BLT NSG) - is prone for cGVHD, yet mainly affects the skin. In contrast, the NSG mouse humanized exclusively with CD34(+)-selected, CD3(+)-depleted stem cells (CD34(+)NSG) has neither been described for acute nor chronic GVHD so far. This is the first report about the development of systemic autoimmune cGVHD >=24 weeks post stem cell receipt involving lung, liver, skin, gingiva and intestine in two NSG cohorts humanized with CD34(+) grafts from different donors. Affected mice presented with sclerodermatous skin, fibrotic lung, severe hepatitis, and massive dental malformation/loss. CD4(+)-dominated, TH2-biased, bulky T-cell infiltrates featured highly skewed T cell receptor (TCR) repertoires, clonal expansions, and autoreactive TCRs. In affected tissues profibrotic IL-13 and -4 dominated over TH1 cytokines IFN-gamma and TNF-alpha. Thus, the time point of manifestation and the phenotype match human systemic pleiotropic sclerodermatous GVHD. The CD34(+)NSG-model's intrinsic deficiency of thymus, thymus-derived regulatory T cells (nTreg) and B cells emphasizes the role of the genetic polymorphism and the cytokines in the pathogenesis of cGVHD. Importantly, the only factor discriminating diseased versus non-diseased CD34(+)NSG cohorts were two risk HLA haplotypes that in human mediate susceptibility for autoimmune disease (psoriasis). Thus, the CD34(+)NSG model may serve as a platform for addressing issues related to the pathophysiology and treatment of human autoimmunity and chronic GVHD. PMID- 26143959 TI - Impulsive Personality, Parental Monitoring, and Alcohol Outcomes From Adolescence Through Young Adulthood. AB - PURPOSE: We examined the time-varying effects of sensation seeking, lack of perseverance, and parental monitoring on heavy drinking and alcohol-related harms from ages 16 to 28 years. METHODS: Participants were from the Victoria Healthy Youth Survey, followed six times, biennially, between 2003 and 2013 (N = 662; mean age at Time 1 = 15.52, range = 12-18). Analyses used time-varying effect models, which estimate how the association between a predictor and an outcome differs over time without assuming the association follows a parametric function of time. RESULTS: Sensation seeking was a stable risk factor for heavy drinking, and lack of perseverance was stable risk factor for alcohol-related harms at each age. Parental monitoring was associated with lower rates of heavy drinking in adolescence and lower rates of alcohol harm until the age of 24 years. Moreover, high levels of parental monitoring moderated the association between personality traits and rates of harm at ages 17-20 years but only for youth high on lack of perseverance and low on sensation seeking. CONCLUSIONS: The results provide a better understanding of age-related changes in risk and protective factors of alcohol use across the transition to adulthood. Impulsive personality traits are stable risk factors for alcohol outcomes until the late-20s despite typical age related declines in these traits and drinking. Moreover, parental monitoring buffers the association between personality traits and alcohol harm for specific youth during the transition to adulthood. Personality-targeted interventions may be effective beyond adolescence, and parenting interventions may help reduce harm among low perseverance, low sensation-seeking youth. PMID- 26143960 TI - [Hospital production cost of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression]. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective and well-tolerated treatment in resistant depression with mild to moderate intensity. This indication has not yet been approved in France. The cost and medico-economic value of rTMS in psychiatry remains unknown. The aim of this preliminary study was to assess rTMS cost production analysis as an in-hospital treatment for depression. METHODS: The methodology, derived from analytical accounts, was validated by a multidisciplinary task force (clinicians, public health doctors, pharmacists, administrative officials and health economist). It was pragmatic, based on official and institutional documentary sources and from field practice. It included equipment, staff, and structure costs, to get an estimate as close to reality as possible. First, we estimated the production cost of rTMS session, based on our annual activity. We then estimated the cost of a cure, which includes 15 sessions. A sensitivity analysis was also performed. RESULTS: The hospital production cost of a cure for treating depression was estimated at ? 1932.94 (? 503.55 for equipment, ? 1082.75 for the staff, and ? 346.65 for structural expenses). CONCLUSION: This cost-estimate has resulted from an innovative, pragmatic, and cooperative approach. It is slightly higher but more comprehensive than the costs estimated by the few international studies. However, it is limited due to structure-specific problems and activity. This work could be repeated in other circumstances in order to obtain a more general estimate, potentially helpful for determining an official price for the French health care system. Moreover, budgetary constraints and public health choices should be taken into consideration. PMID- 26143961 TI - Incidence and predictors of surgical site infection in a general surgery department in Algeria. AB - BACKGROUND: Little is known about the epidemiology of surgical site infection (SSI) in Algeria. To determine the incidence and predictors of SSI in the 70-bed general surgery department at the Blida University Hospital, a 1-year prospective study (May 2006 to April 2007) was conducted. METHODS: SSIs were classified according to the National Nosocomial Infection Surveillance (NNIS) System criteria and identified by bedside surveillance and post-discharge follow-up. Predictors were identified using a logistic regression model. RESULTS: Of 593 surgical procedures, 32 SSIs were identified (5.4%). Twenty-eight (43.8%) of the infections were diagnosed after discharge. The incidence of SSIs varied by procedure and risk category. On multivariate regression analysis, age (OR=1.35) and NNIS risk index (OR=3.02) were significant predictors of SSI. The causative pathogens were isolated in 12 (37.5%) of the 32 recorded SSIs. Staphylococcus aureus was predominant (n=5). CONCLUSION: The high SSI rates reported in this study suggest the need to implement preventive measures in the surgery department. Potential areas for intervention include antibiotic prophylaxis and shaving practices for skin preparation. PMID- 26143962 TI - High reactivity of the cortisol awakening response predicts positive treatment outcome in heterogeneous depressed patients completing an alternate milieu inpatient program. AB - OBJECTIVE: Delineating clinically meaningful subgroups within heterogeneous depressed populations is a major challenge. As outlined in the Research Domain Criteria Strategy, biomarkers may help to empirically classify such patients. Following this basic strategy, the current pilot study examined whether the cortisol awakening response (CAR) following admission to hospital predicts treatment response in heterogeneous depressed patients completing a 4-week alternate milieu inpatient program. METHODS: The Alternate Inpatient Milieu program at the Centre for Addiction and Mental Health is composed of both individual-based and group-based programming designed to promote a recovery oriented, collaborative treatment environment. The current sample consisted of 25 consecutive patients with various forms of complex/chronic depression who completed the full program. Saliva samples were collected at 0, 30 and 60 min after awakening on 2 consecutive days following admission. Linear regressions controlling for baseline depression scores were used to assess whether the CAR AUCg (area under the curve ground) and/or AUCi (area under the curve increase) at admission predicted the change in depression scores from admission to discharge based on the Quick Inventory of Depressive Symptoms scale. RESULTS: The CAR AUCi, but not the CAR AUCg, at admission significantly predicted treatment response over the 4-week hospital stay. In these naturalistic patients with major depressive disorder, high CAR reactivity as assessed using the AUCi was associated with a better treatment response (t=2.20; df=2,24; P=.039). The CAR was easy to implement and well accepted by patients and staff. CONCLUSION: This pilot study suggests that CAR reactivity at admission may help to identify a subgroup of depressed patients most likely to respond clinically to a 4-week alternate milieu inpatient program. PMID- 26143963 TI - Subject identification via ECG fiducial-based systems: influence of the type of QT interval correction. AB - Electrocardiography (ECG) has been recently proposed as biometric trait for identification purposes. Intra-individual variations of ECG might affect identification performance. These variations are mainly due to Heart Rate Variability (HRV). In particular, HRV causes changes in the QT intervals along the ECG waveforms. This work is aimed at analysing the influence of seven QT interval correction methods (based on population models) on the performance of ECG-fiducial-based identification systems. In addition, we have also considered the influence of training set size, classifier, classifier ensemble as well as the number of consecutive heartbeats in a majority voting scheme. The ECG signals used in this study were collected from thirty-nine subjects within the Physionet open access database. Public domain software was used for fiducial points detection. Results suggested that QT correction is indeed required to improve the performance. However, there is no clear choice among the seven explored approaches for QT correction (identification rate between 0.97 and 0.99). MultiLayer Perceptron and Support Vector Machine seemed to have better generalization capabilities, in terms of classification performance, with respect to Decision Tree-based classifiers. No such strong influence of the training-set size and the number of consecutive heartbeats has been observed on the majority voting scheme. PMID- 26143964 TI - Acute Scapholunate Ligament Instability. PMID- 26143965 TI - Bennett Fracture. PMID- 26143966 TI - The Effect of Closed Reduction of Small Finger Metacarpal Neck Fractures on the Ultimate Angular Deformity. AB - PURPOSE: To assess whether or not attempted closed reduction of fifth metacarpal neck fractures results in decreased fracture angulation at final follow-up. METHODS: Retrospective chart review of all patients aged 18 and older managed for isolated fifth metacarpal neck fractures between 2004 and 2014. RESULTS: Sixty six patients managed for an isolated boxer fracture met inclusion criteria. Twenty-three patients underwent attempted reduction and 43 patients did not. Patients undergoing attempted reduction had a statistically significant improvement in fracture angulation following reduction compared with patients not undergoing attempted reduction. At final follow-up, there was no difference in fracture angle between the 2 groups. CONCLUSIONS: Closed reduction and splint immobilization of fifth metacarpal neck fractures was not an effective means of maintaining a significant improvement in fracture alignment upon healing. Other means, such as closed reduction with pin fixation or open reduction internal fixation, should be considered when maintenance of reduction is desired. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 26143967 TI - Surgical Techniques for Correction of Traumatic Hyperextension Instability of the Proximal Interphalangeal Joint: A Biomechanical Study. AB - PURPOSE: To compare the biomechanical strengths of 5 surgical techniques for treatment of traumatic hyperextension instability of the proximal interphalangeal (PIP) joint. METHODS: Thirty-six cadaveric fingers were randomly assigned to 6 groups: normal control, volar plate repair, flexor digitorum superficialis tenodesis (FDST), single lateral band transfer (SLBT), double lateral band transfer, and dual split lateral band transfer. For each experimental specimen, the volar plate and accessory collateral ligaments were transected, the PIP joint was hyperextended to 90 degrees , and a PIP joint stabilizing procedure was completed. The ultimate strength of each procedure was ascertained by loading to failure, and the fingers were dissected to determine the pathoanatomy of failure. Force-displacement curves were used to estimate the stiffness of each group, and multiple pairwise statistical comparisons were performed. RESULTS: The mean PIP joint stiffness in the control group was significantly greater than the mean PIP joint stiffness in the FDST and SLBT groups, but not significantly different from the mean PIP joint stiffness in the other 3 groups. There were no significant differences in the mean PIP joint stiffness between the 5 joint stabilizing techniques. The SLBT, double lateral band transfer, and dual split lateral band transfer repairs all failed by massive disruption of the flexor tendon sheath, whereas the volar plate repairs and FDST repairs failed by either suture anchor pullout or suture breakage. CONCLUSIONS: The stiffness of 5 surgical techniques to stabilize a traumatic hyperextensible PIP joint did not vary significantly. CLINICAL RELEVANCE: The 5 described techniques to stabilize a posttraumatic PIP joint hyperextension deformity may provide for equal restraint to PIP joint hyperextension instability in the early postoperative period. The choice of procedure should take into consideration other factors not studied, including the potential for PIP joint flexion contracture and long-term durability. PMID- 26143968 TI - Joint Arthroplasty With Osteochondral Grafting From the Knee for Posttraumatic or Degenerative Hand Joint Disorders. AB - PURPOSE: To describe the operative procedure and report the clinical outcomes of articular surface reconstruction for various hand joint disorders using autologous osteochondral grafts from the knee. METHODS: Ten patients underwent articular surface reconstruction for hand joint disorders with autologous osteochondral grafts from the patellofemoral joint. Mean patient age was 35 years (range, 15-52 y). The patients were followed for an average of 48 months (range, 16-89 mo). Arthroplasty was performed on the metacarpophalangeal joint in 4 cases, and on the proximal interphalangeal joint in 6 cases. The patients' clinical outcomes were evaluated with joint range of motion, visual analog scale (0-10 points), and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Histological examination was performed in 3 cases after surgery. RESULTS: Graft union was confirmed in all cases without radiographic evidence of resorption or necrosis. Follow-up radiographic examinations showed good graft incorporation without signs of osteoarthritis such as joint space narrowing. The finger flexion extension arc improved significantly from an average of 21 degrees to 61 degrees . The mean visual analog scale also improved significantly from 7.0 to 1.5. The mean total active motion showed a significant improvement from 151 degrees before surgery to 201 degrees after surgery, and the mean DASH score improved significantly from 33 to 12. There were no significant differences for the arc of finger motion and DASH score between metacarpophalangeal and proximal interphalangeal joint disorders or between hemiarthroplasty and total joint arthroplasty. Histological examination revealed viable chondrocytes in the implanted cartilage. CONCLUSIONS: Autologous osteochondral grafting from the patellofemoral joint provided satisfactory outcomes and may be a useful option for joint surface reconstruction of traumatic or degenerative hand joint disorders. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26143969 TI - Editorial overview: Immunomodulation: New insights for future treatments. PMID- 26143970 TI - New insights after the first 1000 liver transplantations at The University of Hong Kong. AB - BACKGROUND/OBJECTIVE: One thousand liver transplantations have been performed at the only liver transplant center in Hong Kong over a period of 22 years, which covered the formative period of living donor liver transplantation. These 1000 transplantations, which marked the journey of liver transplantation from development to maturation at the center, should be educational. This research was to study the experience and to reflect on the importance of technical innovations and case selection. METHODS: The first 1000 liver transplantations were studied. Key technical innovations and surgical therapeutics were described. Recipient survival including hospital mortality was analyzed. Recipient survival comparison was made for deceased donor liver transplantation and living donor liver transplantation indicated by hepatocellular carcinoma and other diseases. RESULTS: Among the 1000 transplantations, 418 used deceased donor grafts and 582 used living donor grafts. With the accumulation of experience, hospital mortality improved to < 2% in the past 2 years. In the treatment of diseases other than hepatocellular carcinoma, living donor liver transplantation was superior to deceased donor liver transplantation, with a 10-year recipient survival around 90%. CONCLUSION: Transplant outcomes have been improving consistently over the series, with a very low hospital mortality and a predictably high long-term survival. PMID- 26143971 TI - Transfer of opiorphin through a blood-brain barrier culture model. AB - Opioid peptides are potent analgesics with therapeutic potential in the treatment of acute and chronic pain. Their efficacy is limited by peptidases (enkephalinases). Opiorphin pentapeptide (QRFSR) is the first characterized human endogenous inhibitor of enkephalinases. The peptide is able to increase the binding and affinity of endogenous opiates to mu opioid receptors; thus, the mechanism of opiorphin may provide a new therapeutic approach in pain management. The analgesic effect of opiorphin was proven in several earlier published in vitro and in vivo studies. Our aim was to test the transfer of opiorphin through a blood-brain barrier model for the first time. The flux of opiorphin was tested on a blood-brain barrier culture model consisting of rat brain endothelial, glial and pericyte cells. Brain endothelial cells in this triple co-culture model form tight monolayers characterized by transendothelial electrical resistance measurement. Relative quantity of the peptide was estimated by mass spectrometry. The transfer of opiorphin through the blood-brain barrier model was estimated to be ~3%, whereas the permeability coefficient was 0.53 +/- 1.36 * 10(-6) cm/s (n = 4). We also observed rapid conversion of N-terminal glutamine into pyroglutamic acid during the transfer experiments. Our results indicate that opiorphin crosses cultured brain endothelial cells in the absence of serum factors in a significant amount. This is in agreement with previous in vivo data showing potentiation of enkephalin-mediated antinociception. We suggest that opiorphin may have a potential as a centrally acting novel drug to treat pain. PMID- 26143972 TI - Sex, steroids, and fear. PMID- 26143973 TI - Oxytocin enhancement of fear extinction: a new target for facilitating exposure based treatments? PMID- 26143974 TI - Trauma re-experiencing symptoms modulate topology of intrinsic functional networks. PMID- 26143992 TI - The ecdysone receptor coactivator Taiman links Yorkie to transcriptional control of germline stem cell factors in somatic tissue. AB - The Hippo pathway is a conserved signaling cascade that modulates tissue growth. Although its core elements are well defined, factors modulating Hippo transcriptional outputs remain elusive. Here we show that components of the steroid-responsive ecdysone (Ec) pathway modulate Hippo transcriptional effects in imaginal disc cells. The Ec receptor coactivator Taiman (Tai) interacts with the Hippo transcriptional coactivator Yorkie (Yki) and promotes expression of canonical Yki-responsive genes. Tai enhances Yki-driven growth, while Tai loss, or a form of Tai unable to bind Yki, suppresses Yki-driven tissue growth. This growth suppression is not correlated with impaired induction of canonical Hippo responsive genes but with suppression of a distinct pro-growth program of Yki induced/Tai-dependent genes, including the germline stem cell factors nanos and piwi. These data reveal Hippo/Ec pathway crosstalk in the form a Yki-Tai complex that collaboratively induces germline genes as part of a transcriptional program that is normally repressed in developing somatic epithelia. PMID- 26143993 TI - Somatic cell encystment promotes abscission in germline stem cells following a regulated block in cytokinesis. AB - In many tissues, the stem cell niche must coordinate behavior across multiple stem cell lineages. How this is achieved is largely unknown. We have identified delayed completion of cytokinesis in germline stem cells (GSCs) as a mechanism that regulates the production of stem cell daughters in the Drosophila testis. Through live imaging, we show that a secondary F-actin ring is formed through regulation of Cofilin activity to block cytokinesis progress after contractile ring disassembly. The duration of this block is controlled by Aurora B kinase. Additionally, we have identified a requirement for somatic cell encystment of the germline in promoting GSC abscission. We suggest that this non-autonomous role promotes coordination between stem cell lineages. These findings reveal the mechanisms by which cytokinesis is inhibited and reinitiated in GSCs and why such complex regulation exists within the stem cell niche. PMID- 26143994 TI - A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation. AB - Increasing evidence suggests that long non-coding RNAs (LncRNAs) represent a new class of regulators of stem cells. However, the roles of LncRNAs in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of intergenic LncRNAs were identified that are expressed in myoblasts and regulated during differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation, largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mRNA binding protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the RNA sequence of LncMyoD is not well conserved between human and mouse, its locus, gene structure, and function are preserved. The MyoD-LncMyoD-IMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation. PMID- 26143995 TI - Place memory retention in Drosophila. AB - Some memories last longer than others, with some lasting a lifetime. Using several approaches memory phases have been identified. How are these different phases encoded, and do these different phases have similar temporal properties across learning situations? Place memory in Drosophila using the heat-box provides an excellent opportunity to examine the commonalities of genetically defined memory phases across learning contexts. Here we determine optimal conditions to test place memories that last up to three hours. An aversive temperature of 41 degrees C was identified as critical for establishing a long lasting place memory. Interestingly, adding an intermittent-training protocol only slightly increased place memory when intermediate aversive temperatures were used, and slightly extended the stability of a memory. Genetic analysis of this memory identified four genes as critical for place memory within minutes of training. The role of the rutabaga type I adenylyl cyclase was confirmed, and the latheo Orc3 origin of recognition complex component, the novel gene encoded by pastrel, and the small GTPase rac were all identified as essential for normal place memory. Examination of the dopamine and ecdysone receptor (DopEcR) did not reveal a function for this gene in place memory. When compared to the role of these genes in other memory types, these results suggest that there are genes that have both common and specific roles in memory formation across learning contexts. Importantly, contrasting the timing for the function of these four genes, plus a previously described role of the radish gene, in place memory with the temporal requirement of these genes in classical olfactory conditioning reveals variability in the timing of genetically-defined memory phases depending on the type of learning. PMID- 26143996 TI - The role of chromatin repressive marks in cognition and disease: A focus on the repressive complex GLP/G9a. AB - Histone post-translational modifications are key epigenetic processes controlling the regulation of gene transcription. In recent years it has become apparent that chromatin modifications contribute to cognition through the modulation of gene expression required for the expression and consolidation of memories. In this review, we focus on the role of histone methylation in the nervous system. Histone methylation is involved in a number of cognitive disturbances, such as intellectual disability, cocaine addiction and age-related cognitive decline. We provide an overview of the dynamic changes in methylation of histone lysine residues during learning and memory. With a special focus on H3K9 histone methyltransferases GLP and G9a, we summarize the effects of deficiencies in writer and eraser enzymes on neuronal plasticity and cognition. PMID- 26143997 TI - [Practical problems related to the management of febrile urinary tract infection in Vietnamese children]. AB - BACKGROUND: To describe the practical problems related to urinary tract infection (UTI) management in febrile Vietnamese children. METHODS: During a prospective 28 month inclusion period, 143 febrile children with significant bacteriuria were treated for UTI in the nephrology department of Nhi Dong 2 children's hospital in Ho Chi Minh City, Vietnam. Patients were treated after blood and urine samples had been taken for culture, according to a local antibiotic protocol, parenterally with ceftriaxone 75mg/kg/day. Oral treatment with cefixime 8mg/kg/day was started after 48h of apyrexia for 2 weeks. According to local protocol, antibiotic therapy was only changed if children did not respond clinically to treatment regardless of antibiogram results. RESULTS: Among these 143 children, 51% were girls and 80% of them had their first UTI before the age of 2 years. The commonest causative agent was Escherichia coli (80% of cases) with a high resistance rate to ampicillin (91%) and cotrimoxazole (74%). Extended spectrum beta-lactamase (ESBL) production was observed in 52% of Enterobacteriaceae isolates. According to antibiotic susceptibility, the initial treatment with ceftriaxone was found to be inappropriate in 63% of cases. CONCLUSIONS: E. coli was responsible for 80% of UTIs in Vietnamese children with a high rate of resistance to first-line antibiotics. ESBL production was found to be extremely high in this study. Based on these data, we propose a new empiric treatment schedule for Vietnamese children suspected of UTI. PMID- 26143998 TI - [Oxidative stress after preterm birth: origins, biomarkers, and possible therapeutic approaches]. AB - The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso prostaglandin F2alpha, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future. PMID- 26143999 TI - Management of subacute acetabular osteomyelitis in a child. AB - Clinical manifestations of subacute osteomyelitis may lead to delayed diagnosis. Acetabular subacute osteomyelitis is an uncommon disease. Bone tumors are usually suggested first. Diagnosis is often made based on radiological findings. We report on the case of a 9-year-old girl who consulted at the emergency department because of limping and pain in her left limb lasting 2 weeks. No fever was reported. Physical examination found a clear, painful reduction in hip mobility. X-ray findings revealed a posterior loss of bone in the acetabular wall. MRI found a mild invasion of the periarticular hip joint and muscles. The surgical exploration of the hip found a collection in the posterior acetabular wall suggesting septic disease. Bacteriological and pathological exams confirmed acetabular subacute osteomyelitis. Nine months after surgery, antibiotic therapy, and physiotherapy, the patient was painless and the hip mobility showed near normal values with a reduction in external rotation and flexion. The aim of this case report is to review the characteristics of subacute acetabular osteomyelitis, including therapeutic modalities, underlining surgical debridement as a rule for both diagnosis and treatment. PMID- 26144000 TI - Myasthenia gravis and the neurology of inflammatory bowel disease. PMID- 26144017 TI - The role of protein-protein interactions in Toll-like receptor function. AB - As part of the innate immune system, the Toll-like receptors (TLRs) represent key players in the first line of defense against invading foreign pathogens, and are also major targets for therapeutic immunomodulation. TLRs are type I transmembrane proteins composed of an ectodomain responsible for ligand binding, a single-pass transmembrane domain, and a cytoplasmic Toll/Interleukin-1 receptor (TIR) signaling domain. The ectodomains of TLRs are specialized for recognizing a wide variety of pathogen-associated molecular patterns, ranging from lipids and lipopeptides to proteins and nucleic acid fragments. The members of the TLR family are highly conserved and their ectodomains are composed of characteristic, solenoidal leucine-rich repeats (LRRs). Upon ligand binding, these rigid LRR scaffolds dimerize (or re-organize in the case of pre-formed dimers) to bring together their carboxy-terminal transmembrane and TIR domains. The latter are proposed to act as a platform for recruitment of adaptor proteins and formation of higher-order complexes, resulting in propagation of downstream signaling cascades. In this review, we discuss the protein-protein interactions critical for formation and stability of productive, ligand-bound TLR complexes. In particular, we focus on the large body of high-resolution crystallographic data now available for the ectodomains of homo- and heterodimeric TLR complexes, as well as inhibitory TLR-like receptors, and also consider computational approaches that can facilitate our understanding of the ligand-induced conformational changes associated with TLR function. We also briefly consider what is known about the protein-protein interactions involved in both TLR transmembrane domain assembly and TIR-mediated signaling complex formation in light of recent structural and biochemical data. PMID- 26144018 TI - Early Precut Sphincterotomy Does Not Increase Risk During Endoscopic Retrograde Cholangiopancreatography in Patients With Difficult Biliary Access: A Meta analysis of Randomized Controlled Trials. AB - BACKGROUND & AIMS: Use of precut sphincterotomy during endoscopic retrograde cholangiopancreatography (ERCP) can increase the odds for cannulation success but is associated with increased risk of post-ERCP pancreatitis. Earlier, rather than delayed, use of precut sphincterotomy for cases with difficult biliary access might reduce this risk. We performed a meta-analysis of randomized controlled trials to determine how early use of precut sphincterotomy affects the risk of pancreatitis and rate of cannulation success compared with persistent standard cannulation. METHODS: We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials, along with meeting abstracts, through August 2014 for randomized controlled trials in which early precut sphincterotomy was compared with persistent standard cannulation in adults with difficult biliary access. Outcomes considered included primary cannulation success, overall cannulation success, incidence of post-ERCP pancreatitis, and overall adverse event rate. Findings from a random-effects model were expressed as pooled risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: We analyzed data from 5 studies (523 participants). The incidence of post-ERCP pancreatitis and success of overall cannulation did not differ significantly between the early precut and persistent standard therapy groups. Early use of precut sphincterotomy was associated with increased odds for primary cannulation success (RR, 1.32; 95% CI, 1.04-1.68). In subgroup analysis of studies that involved only fully qualified biliary endoscopists (not fellows), we found a significant reduction in risk of pancreatitis among patients receiving early precut vs the standard technique (RR, 0.29; 95% CI, 0.10-0.86). CONCLUSION: Compared with standard therapy, early use of precut sphincterotomy did not increase the risk of post-ERCP pancreatitis in a meta-analysis. When the procedure is performed by qualified biliary endoscopists, early precut can reduce the risk of post-ERCP pancreatitis. Rates of primary cannulation increase with early precut. Further studies are needed to confirm these findings. PMID- 26144019 TI - Species and distribution of inorganic and organic phosphorus in enhanced phosphorus removal aerobic granular sludge. AB - The species and distribution of phosphorus (P) in an enhanced biological phosphorus removal (EBPR)-aerobic granular sludge (AGS) were fractionated and further analyzed. Results showed that microbial cells, extracellular polymeric substances (EPS) and mineral precipitates contributed about 73.7%, 17.6% and 5.3 6.4% to the total P (TP) of EBPR-AGS, respectively. Inorganic P (IP) species were orthophosphate, pyrophosphate and polyphosphate among which polyphosphate was the major P species in the AGS, cells and EPS. Monoester and diester phosphates were identified as the organic P (OP) species in the AGS and cells. Hydroxyapatite (Ca5(PO4)3OH) and calcium phosphate (Ca2(PO4)3) were the dominant P minerals accumulated in the core of the granules. Cells along with polyphosphate were mainly in the outer layer of AGS while EPS were distributed in the whole granules. Based on the above results, the distribution of IP and OP species in AGS has been conceived. PMID- 26144020 TI - The effects of microbial fuel cell integration into constructed wetland on the performance of constructed wetland. AB - The present work is the first detailed study, which is about the performance of CW after MFC integration with it. The experiments were run in open and closed circuit mode for assessment purpose. The findings of this study indicate towards a more practical application of MFC in wastewater treatment along with electricity production. The closed circuit operations of CW-MFCs have performed 12-20% better than open circuit operation and 27-49% better than Normal-CW for chemical oxygen demand (COD) removal. The maximum power density of 320.8 mW/m(3) and current density of 422.2 mA/m(3) have been achieved in granular graphite anode and Pt coated carbon cloth cathode based CW-MFC. PMID- 26144021 TI - Sleep disorders in pregnancy. PMID- 26144022 TI - Overview of the health care system in Hong Kong and its referential significance to mainland China. AB - Hong Kong's health system was established within the framework of a perfect market-oriented economic matrix, where there are wide-ranging social security and medical service systems. There are many differences in the economic foundations, social systems, and ideologies between Hong Kong and mainland China, therefore, it would probably be entirely impossible to copy Hong Kong's health care system mode. However, under the framework of one country, two systems, the referential significance of relevant concepts of Hong Kong's medical service system to mainland China cannot be ignored, and merits further study. PMID- 26144023 TI - The outcome of 5-fluorouracil chemotherapy after the completion of neoadjuvant chemoradiotherapy, administered until 2 weeks before rectal cancer resection. AB - BACKGROUND: In most institutions, locally advanced rectal cancer is treated with neoadjuvant chemoradiotherapy followed by surgery 6-8 weeks later, allowing time for tumor response and recovery from chemoradiotherapy-related toxicities. In our hospital, we continuously administer chemotherapy after the completion of chemoradiotherapy, until 2 weeks before surgery for most patients. METHODS: This was a retrospective study. Patients received a diagnosis of adenocarcinoma of the rectum at our hospital between January 2003 and December 2008 and received neoadjuvant chemoradiotherapy and curative surgery. Chemoradiotherapy consisted of continuous infusion of 225 mg/m(2) 5-fluorouracil, 5 days per week. Radiation therapy was delivered at 1.8 Gy per day, 5 days per week for 5-6 weeks (median radiation dose, 50.4 Gy). Chemotherapy was continued until 2 weeks before surgery, and surgery was performed 6-8 weeks after completion of chemoradiotherapy. RESULTS: The study included 119 patients (median age, 61 years; range, 24-84 years). Twenty-nine patients (24.4%) had a complete response and 65 (54.6%) had a partial response. Over a median follow-up duration of 52 months, 10 patients experienced local recurrence and 18 had distant metastasis. The 5-year overall and disease-free survival rates were 80.6% and 72.9%, respectively. Grade 3-4 toxicity only occurred in 14 patients (11.8%). CONCLUSION: Continued chemotherapy with 5-fluorouracil after completing neoadjuvant chemoradiotherapy until 2 weeks before surgery for locally advanced rectal cancer results in a good pathological control rate, with low toxicity. Patients who achieved a complete pathological response had a better long-term oncological outcome than those who did not. PMID- 26144024 TI - The effect of inbreeding constraints and offspring distribution on time to the most recent common ancestor. AB - The expected time to the most recent common ancestor (MRCA) of two alleles in a diploid individual is 4N+2 under random mating with a Poisson progeny distribution, but 8N-2 under maximum avoidance of inbreeding, which entails two progeny per mating pair. (N is the number of mating pairs, hence 2N is the number of individuals, hence 4N is the number of alleles.) The interrelationship of inbreeding constraints and offspring distribution is investigated by varying the level of sib mating: prohibiting sib mating increases the time to MRCA by four generations and decreases the variance of the offspring distribution by 2/N. With two progeny per mating pair, the expected time to the MRCA is 8N-2 under both random mating and sib mating prohibited, as well as under maximum avoidance of inbreeding, but this result does not hold for all mating structures with two progeny per mating pair. PMID- 26144046 TI - Complete genome sequence of the petroleum-emulsifying bacterium Pseudomonas stutzeri SLG510A3-8. AB - Pseudomonas stutzeri SLG510A3-8, isolated from oil-contaminated soil in Shengli Oilfield, China, has the potential to be applied for microbial enhanced oil recovery. Here, we reported the complete genome sequence of this bacterium. It has a 4,650,155bp circular chromosome encoding 4450 genes, and the genome consists of genes that are involved in denitrification, chemotaxis, benzoate degradation, molecule transportation, and other functions. The genome contains a complete set of genes for type I secretion system in comparison with sequences of other P. stutzeri strains. PMID- 26144048 TI - Positive feedback of DDX6/c-Myc/PTB1 regulated by miR-124 contributes to maintenance of the Warburg effect in colon cancer cells. AB - The human DEAD/H-box RNA helicase gene DDX6 is a target of the t(11;14)(q23;q32) chromosomal translocation observed in human B-cell lymphoma, and the overexpression of its protein has been shown to cause malignant transformation. DDX6 has a variety of functions such as translation initiation, pre-mRNA splicing, ribosome assembly, and more. However, details of the regulatory mechanism of DDX6 and functions of DDX6 in cancer cells are largely unknown. On the other hand, the Warburg effect is a well-known feature of cancer cells. Pyruvate kinase in muscle (PKM), which is a rate-limiting glycolytic enzyme, has 2 isoforms, PKM1 and PKM2. It has been frequently reported that PKM2 is a tumor specific isoform and promotes the Warburg effect. However, the functions of the PKM1 gene have been hardly mentioned. Here, we showed that DDX6 was overexpressed in colorectal cancer specimens and regulated by microRNA (miR)-124 in colon cancer cells. Also, a DDX6/c-Myc/PTB1 positive feedback circuit regulated by miR 124 was shown to be established and to contribute to maintenance of the Warburg effect. Moreover, we showed that knockdown of DDX6 induced mainly apoptosis through an imbalance of PKM gene expression, especially causing down-regulation of PKM1 in colon cancer cells. These results suggest that miR-124 is a fine tuner of the Warburg effect and that DDX6 is one of the key molecules in Warburg effect related miR-124 targeting various genes. PMID- 26144047 TI - Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways. AB - Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-alpha levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity. PMID- 26144050 TI - Why do humans have two glucocorticoids: A question of intestinal fortitude. AB - The main purpose of this review article is threefold (a) to try to address the question "why are two adrenal glucocorticoids, cortisol and corticosterone, secreted by humans and other mammalian species?", (b) to outline a hypothesis that under certain physiological conditions, corticosterone has additional biochemical functions over and above those of cortisol, and (c) to emphasize the role of gastrointestinal bacteria in chemically transforming corticosterone into metabolites and that these re-cycled metabolites can be reabsorbed from the enterohepatic circuit. Cortisol and its metabolites are not secreted into the bile and thus are excluded from the enterohepatic circuit. Corticosterone was the first steroid hormone isolated from adrenal gland extracts. Many believe that corticosterone functions identically to cortisol. Yet, corticosterone causes significant sodium retention and potassium secretion in Addisonian patients, unlike cortisol. In humans, corticosterone and its metabolite, 3alpha,5alpha-TH corticosterone, are excreted via the bile in humans where they are transformed in the intestine by anaerobic bacteria into 21-dehydroxylated products: 11beta-OH progesterone or 11beta-OH-(allo)-5alpha-preganolones. These metabolites inhibit 11beta-HSD2 and 11beta-HSD1 dehydrogenase, being many-fold more potent than 3alpha,5alpha-TH-cortisol. Corticosterone has significantly lower Km's for both 11beta-HSD2 and 11beta-HSD1 enzymatic dehydrogenase activity, compared to cortisol. Patients diagnosed with 17alpha-hydroxylase deficiency have elevated blood pressure and high levels of circulating corticosterone, 3alpha,5alpha-TH corticosterone, and their 21-dehydroxlated corticosterone derivatives. In humans, these 5alpha-corticosterone metabolites are likely to influence blood pressure regulation and Na(+) retention by inhibiting the rate of deactivation of cortisol by 11beta-HSD isoforms. PMID- 26144049 TI - The role of folate metabolism in orofacial development and clefting. AB - Folate deficiency has been associated with numerous diseases and birth defects including orofacial defects. However, whether folate has a role in the face during early orofacial development has been unclear. The present study reveals that pharmacological and antisense oligonucleotide mediated inhibition of DHFR, an integral enzyme in the folate pathway, results in specific changes in the size and shape of the midface and embryonic mouth. Such defects are accompanied by a severe reduction in the muscle and cartilage jaw elements without significant change in neural crest pattern or global levels of methylation. We propose that the orofacial defects associated with DHFR deficient function are the result of decreased cell proliferation and increased cell death via DNA damage. In particular, localized apoptosis may also be depleting the cells of the face that express crucial genes for the differentiation of the jaw structures. Folate supplementation is widely known to reduce human risk for orofacial clefts. In the present study, we show that activating folate metabolism can reduce median oral clefts in the primary palate by increasing cell survival. Moreover, we demonstrate that a minor decrease in DHFR function exacerbates median facial clefts caused by RAR inhibition. This work suggests that folate deficiencies could be a major contributing factor to multifactorial orofacial defects. PMID- 26144063 TI - Modulation of aryl hydrocarbon receptor-regulated enzymes by trimethylarsine oxide in C57BL/6 mice: In vivo and in vitro studies. AB - Arsenic is a worldwide environmental pollutant that is associated with skin and several types of internal cancers. Recent reports revealed that arsenic biomethylation could activate the toxic and carcinogenic potential of arsenic. Therefore, we investigated the effect of trimethylarsine oxide (TMAO) on the activation of AhR-regulated genes in vivo and in vitro. In vivo, C57BL/6 mice received TMAO (13mg/kg i.p.) with or without the prototypical AhR ligand, TCDD (15MUg/kg), then the livers were harvested at 6 and 24h post-treatment. In vitro, isolated hepatocytes from C57BL/6 mice were treated with TMAO (5MUM) in the absence and presence of TCDD (1nM) for 6 and 24h. Our in vivo results demonstrated that, TMAO alone increased Cyp1a1, Cyp1a2, Cyp1b1, Nqo1, Gsta1, and Ho-1 at mRNA level. Upon co-exposure to TMAO and TCDD, TMAO potentiated the TCDD mediated induction of Cyp1a1, Cyp1b1, and Nqo1 mRNA levels. Western blotting revealed that, TMAO alone increased Cyp1a1, Cyp1a2, Nqo1, Gsta1/2, and Ho-1 protein levels, and potentiated the TCDD-mediated induction of Cyp1a1 and Cyp1b1 protein level. In addition, TMAO alone significantly increased Cyp1a1, Cyp1a2, Nqo1, Gst, and Ho-1 activities and significantly potentiated the TCDD-mediated induction of Cyp1a1 activity. At the in vitro level, TMAO induced Cyp1a1 and potentiated the TCDD-mediated induction of Cyp1a1 at mRNA, protein and activity levels. In addition, TMAO increased the nuclear localization of AhR and AhR dependent XRE-driven luciferase activity. Our results demonstrate that the TMAO, modulates AhR-regulated genes which could potentially participate, at least in part, in arsenic induced toxicity and carcinogenicity. PMID- 26144064 TI - Comparing antioxidant enzyme levels in follicular fluid in ICSI-treated patients. AB - OBJECTIVES: Oxidant-antioxidant imbalance has an adverse effect on all stages of reproduction. Follicular fluid levels of superoxide dismutase (SOD) and catalase, and the rate of embryo development were compared in women at early perimenopausal and childbearing age, undergoing intracytoplasmic sperm injection (ICSI). METHODS: Patients (n=168) were divided: 110 women at childbearing age (27-35), and 58 aged 40-46. SOD and catalase levels were determined using spectrophotometry, and embryo culture assessed every 10 minutes. RESULTS: Statistically significant differences were observed between the number of pregnancies at child-bearing age (30.91%) and early perimenopause (3.45%) (Chi(2)=15.417, df=1, P=0.0001); also between the rate of embryo development from pronuclear to 4-cell stage, and to achievement of blastocyst stage. This rate was faster in women at childbearing age than those older. SOD levels were lower in younger than older women (Z=-8.473, P<0.001). Catalase levels were significantly higher in patients at childbearing age than those aged 40-46 (Z=-8.473, P<0.001). On the basis of the Kruskal-Wallis test, the group of younger patients showed the occurrence of a statistically significant correlation between the class of embryos, assessed on the second day of observation, and SOD concentration, in which class A showed a mean of 31.83 U/mL, whereas SOD for the B class was -27.61 (H=9.380, P=0.009). During the inner cell mass (ICM) and trophectoderm (TE) assessments in both groups, higher mean SOD concentration accompanied the highest quality of embryos, but statistically significant correlations concerned only older patients in the case of ICM (H=8.476, P=0.014) and TE (H=8.251, P=0.016). CONCLUSIONS: The rate of embryo development decreases with age. In early perimenopause, SOD levels increase, while catalase levels decrease. Additionally, in early perimenopause, SOD activity shortens the time in which 4-cell stage is achieved, while catalase activity delays the 5-cell and blastocyst stages. The quality of embryos has no association with catalase concentration. SOD concentration is associated with the good quality of embryo on the second day of development. The quality of blastocyst in patients in the early perimenopausal age is dependent on SOD concentration. However, the most important prognostic factor of pregnancy after ICSI is age. PMID- 26144065 TI - [Obstetric outcomes after uterine compression suture for treatment of postpartum hemorrhage: Long-term monitoring of 40 cases]. AB - OBJECTIVE: Uterine atony is the first cause of postpartum hemorrhage. In caesarean section, different techniques of uterine compression suture exist when uterotonic drugs fail. Their effectiveness is shown but little data on their effects on subsequent pregnancies are available. The aim of this work is analyze of the obstetrical long-term consequences after uterine compression suture. PATIENTS AND METHODS: This is a retrospective study of 40 cases of uterine compression suture performed in a level III maternity, between 2004 and 2010. The main objective is the evaluation of the obstetrical prognosis of subsequent pregnancies. The efficacy and safety of surgical techniques, according to their transfixing character or not, were analyzed. RESULTS: Eleven pregnancies after uterine compression suture were reported among 14 women whishing another pregnancy. The median time to be pregnant was 27 months (6-78 months). Nine pregnancies were conducted at term. One case of intrauterine growth restriction and a moderate prematurity at 32 weeks were observed. There was no significant difference in efficacy and early surgical complications according to the surgical technique; however, both infectious and ischemic complications were observed after transfixing compression suture. CONCLUSION: The obstetric prognosis after a uterine compression suture is kept. The transfixing techniques may cause more infectious and ischemic complications. An evaluation of surgical techniques depending on their transfixing, or not, character on a large cohort is necessary for the evaluation of the influence of the technique on fertility and postoperative complications. PMID- 26144066 TI - Diabetes, obesity, and the metabolic syndrome: a call for papers for EASD and the World Diabetes Congress. PMID- 26144102 TI - Pulmonary arterial hypertension in von Recklinghausen's disease. PMID- 26144101 TI - National Trends in Ambulatory Oral Anticoagulant Use. AB - BACKGROUND: Four direct oral anticoagulants (DOACs) have been brought to market for the treatment of nonvalvular atrial fibrillation and venous thromboembolism. Many forces, including numerous positive trial results, emerging safety concerns, marketing, and promotion, may shape DOAC adoption by providers. However, relatively little is known regarding their ambulatory utilization compared with warfarin, as well as the degree to which they have decreased under-treatment of atrial fibrillation. METHODS: We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of outpatient office visits, to estimate the use of warfarin and DOACs between 2009 and 2014. RESULTS: Overall, visits with anticoagulation use increased from 2.05 (95% confidence interval [CI], 1.82-2.27) to 2.83 (95% CI, 2.49-3.17) million (M) quarterly visits (P < .001). Of these, DOAC use has grown to 4.21M (95% CI, 3.63M-4.79M; 38.2% of total) treatment visits in 2014 since their introduction in 2010. Use of all oral anticoagulants in treatment visits for atrial fibrillation has increased from 0.88M (95% CI, 0.74M-1.02M) to 1.72M (95% CI, 1.47M-1.97M; P < .001), with similar DOAC and warfarin use in 2014. Atrial fibrillation visits with anticoagulant use increased from 51.9% (95% CI, 50.4%-53.8%) to 66.9% (95% CI, 65.0%-69.3%) between 2009 and 2014 (P < .001). In 2014, rivaroxaban was the most commonly prescribed DOAC for atrial fibrillation (47.9% of office visits), followed by apixaban (26.5%) and dabigatran (25.5%). CONCLUSIONS: Direct oral anticoagulants have been adopted rapidly, matching the use of warfarin, and are associated with increased use of oral anticoagulation for patients with atrial fibrillation. PMID- 26144103 TI - Inadequacies of Physical Examination as a Cause of Medical Errors and Adverse Events: A Collection of Vignettes. AB - BACKGROUND: Oversights in the physical examination are a type of medical error not easily studied by chart review. They may be a major contributor to missed or delayed diagnosis, unnecessary exposure to contrast and radiation, incorrect treatment, and other adverse consequences. Our purpose was to collect vignettes of physical examination oversights and to capture the diversity of their characteristics and consequences. METHODS: A cross-sectional study using an 11 question qualitative survey for physicians was distributed electronically, with data collected from February to June of 2011. The participants were all physicians responding to e-mail or social media invitations to complete the survey. There were no limitations on geography, specialty, or practice setting. RESULTS: Of the 208 reported vignettes that met inclusion criteria, the oversight was caused by a failure to perform the physical examination in 63%; 14% reported that the correct physical examination sign was elicited but misinterpreted, whereas 11% reported that the relevant sign was missed or not sought. Consequence of the physical examination inadequacy included missed or delayed diagnosis in 76% of cases, incorrect diagnosis in 27%, unnecessary treatment in 18%, no or delayed treatment in 42%, unnecessary diagnostic cost in 25%, unnecessary exposure to radiation or contrast in 17%, and complications caused by treatments in 4%. The mode of the number of physicians missing the finding was 2, but many oversights were missed by many physicians. Most oversights took up to 5 days to identify, but 66 took longer. Special attention and skill in examining the skin and its appendages, as well as the abdomen, groin, and genitourinary area could reduce the reported oversights by half. CONCLUSIONS: Physical examination inadequacies are a preventable source of medical error, and adverse events are caused mostly by failure to perform the relevant examination. PMID- 26144104 TI - Glasgow Coma Creep: Problems of Recognition and Communication. PMID- 26144188 TI - Permanent teeth pulpotomy survival analysis: retrospective follow-up. AB - OBJECTIVES: The aim of the present study is to evaluate risk factors influencing the success rates of pulpotomies both in young and adult populations. METHODS: Pulpotomies (n=273) performed by a single endodontic specialist were analyzed, and data on success rates were collected. Additionally, possible explanatory variables were noted such as: age, gender, clinical findings (teeth, type of restoration after pulpotomy), radiographic findings (dentin bridge formation) and systemic conditions. The follow-up period varied from 1 to 29 years, and the results were analyzed by Kaplan-Meier survival curves and also by Cox regression. RESULTS: Age at the time of pulpotomy ranged from 8 to 79 and had not influenced the success rates (p=0.35). The formation of dentin bridge had a strong protective effect (hazard ratio-HR=0.16, p<0.001). The prosthetic crown restorations following pulpotomy had the smallest failure rate, and amalgam has not increased the risk of failure significantly in relation to prosthesis. Resin composite restorations following pulpotomy increased in 263% the risk of failure (HR=3.63, p<0.001). CONCLUSION: This study allowed inferences that pulpotomy may be a successful treatment at any age, and not only for young permanent teeth. It was also possible to conclude that the use of direct composite restorations following pulpotomies is associated with higher failure rates. PMID- 26144189 TI - Compositional design and optimization of dentin adhesive with neutralization capability. AB - OBJECTIVES: The objective of this work was to investigate the polymerization behavior, neutralization capability, and mechanical properties of dentin adhesive formulations with the addition of the tertiary amine co-monomer, 2-N morpholinoethyl methacrylate (MEMA). METHODS: A co-monomer mixture based on HEMA/BisGMA (45/55, w/w) was used as a control adhesive. Compared with the control formulation, the MEMA-containing adhesive formulations were characterized comprehensively with regard to water miscibility of liquid resin, water sorption and solubility of cured polymer, real-time photopolymerization kinetics, dynamic mechanical analysis (DMA), and modulated differential scanning calorimetry (MDSC). The neutralization capacity was characterized by monitoring the pH shift of 1mM lactic acid (LA) solution, in which the adhesive polymers were soaked. RESULTS: With increasing MEMA concentrations, experimental copolymers showed higher water sorption, lower glass transition temperature and lower crosslinking density compared to the control. The pH values of LA solution gradually increased from 3.5 to about 6.0-6.5 after 90 days. With the increase in crosslinking density of the copolymers, the neutralization rate was depressed. The optimal MEMA concentration was between 20 and 40 wt%. CONCLUSIONS: As compared to the control, the results indicated that the MEMA-functionalized copolymer showed neutralization capability. The crosslinking density of the copolymer networks influenced the neutralization rate. PMID- 26144209 TI - Fertilisation of cryopreserved sperm and unfertilised quail ovum by intracytoplasmic sperm injection. AB - Intracytoplasmic sperm injection (ICSI) is an important technique in animal biotechnology for animal cloning and conservation of genetic resources, but has been a challenge for avian species. In the present study, we investigated the ability of cryopreserved quail spermatozoa to achieve fertilisation and embryo development. Female quail were killed 70-120min after previous oviposition to collect unfertilised oocytes from the oviduct. Fresh or cryopreserved-thawed spermatozoa were injected into the cytoplasm of unfertilised oocytes, and the manipulated oocytes were incubated in quail surrogate eggshells. Injection of fresh spermatozoa supplemented with inositol 1,4,5-trisphosphate (IP3) resulted in a significantly increased rate of embryo development compared with injection of fresh spermatozoa alone (90% vs 13%, respectively). Although >80% of embryos stopped cell division and development before Hamburger and Hamilton (HH) Stage 3, approximately 15% of embryos from the fresh sperm injection developed to past HH Stage 4, and one embryo survived up to HH Stage 39 (11 days of incubation). In the case of cryopreserved spermatozoa, the embryo development rate was 30% after ICSI, and this increased significantly to 74% with IP3 supplementation. In conclusion, cryopreserved spermatozoa combined with ICSI followed by surrogate eggshell culture can develop quail embryos. PMID- 26144210 TI - Synthesis and Bioactivity of a Brasilicardin A Analogue Featuring a Simplified Core. AB - An analogue 2 of Brasilicardin A, 1 (BraA), a potent immunosuppressive and cytotoxic agent, was synthesized in which the natural tricyclic skeleton was replaced with a synthetically more accessible substituted tetrahydronaphthalene core. BraA, this analogue (BraL), and cyclosporine A were tested for their ability to inhibit the proliferation of human T cells upon CD3/CD28 activation. Although BraL did not impact T cell activation over the dose range tested, this study shows the inhibitory activity of BraA on human T cells for the first time. PMID- 26144190 TI - Rechargeable dental adhesive with calcium phosphate nanoparticles for long-term ion release. AB - OBJECTIVES: The tooth-resin bond is the weak link of restoration, with secondary caries as a main reason for failure. Calcium phosphate-containing resins are promising for remineralization; however, calcium (Ca) and phosphate (P) ion releases last only a couple of months. The objectives of this study were to develop the first rechargeable CaP bonding agent and investigate the key factors that determine CaP ion recharge and re-release. METHODS: Nanoparticles of amorphous calcium phosphate (NACP) were synthesized. Pyromellitic glycerol dimethacrylate (PMGDM), ethoxylated bisphenol-A dimethacrylate (EBPADMA), 2 hydroxyethyl methacrylate (HEMA), and bisphenol-A glycidyl dimethacrylate (BisGMA) were used to synthesize three adhesives (denoted PE, PEH and PEHB). NACP were mixed into adhesive at 0-30% by mass. Dentin shear bond strengths were measured. Adhesive specimens were tested for Ca and P initial ion release. Then the ion-exhausted specimens were immersed in Ca and P solution to recharge the specimens, and the recharged specimens were then used to measure ion re-release for 7 days as one cycle. Then these specimens were again recharged and the re release was measured for 7 days as the second cycle. Three recharge/re-release cycles were tested. RESULTS: PEHB had the highest dentin bond strength (p<0.05). Increasing NACP content from 0 to 30% did not affect dentin bond strength (p>0.1), but increased CaP release and re-release (p<0.05). PEHB-NACP had the greatest recharge/re-release, and PE-NACP had the least (p<0.05). Ion release remained high and did not decrease with increasing the number of recharge/re release cycles (p>0.1). After the third cycle, specimens without further recharge had continuous CaP ion release for 2-3 weeks. SIGNIFICANCE: Rechargeable CaP bonding agents were developed for the first time to provide long-term Ca and P ions to promote remineralization and reduce caries. Incorporation of NACP into adhesive had no negative effect on dentin bond strength. Increasing NACP filler level increased the ion recharge and re-release capability. The new CaP recharge method and PMGDM-EBPADMA-NACP composition may have wide application in adhesives, composites and cements, to combat caries and remineralize lesions. PMID- 26144211 TI - Structural morphologies of high-pressure polymorphs of strontium hydrides. AB - It is now known that the structure and properties of a material can be significantly altered under extreme compression. In this work, a structural search was performed to investigate the phase stabilities and structures of SrH2n (n = 1-5) in the pressure range of 50-300 GPa. The high-pressure polymorphs reveal a variety of hydrogen structural units ranging from monatomic hydride to linear and bent H3 and spiral polymer chains. A novel graphene like H-layer structure was found to exist in SrH10 at 300 GPa. The structural diversity in the predicted high pressure structures provides an opportunity for an in-depth analysis of the chemical bonding in the high pressure polyhydrides. It is shown from theoretical calculations that the electronegativity of molecular hydrogen is similar to that of group 13 and 14 elements. This resulted in electrons being transferred from Sr to the hydrogen molecules. Thus, a consideration of the number of valence electrons available from Sr that can be shared among the H2 serves as a useful guide to rationalize the structures of the H-moieties. An alternative description of the high pressure structures differing from a previous study is presented here. PMID- 26144212 TI - Realization of a quantum Hamiltonian Boolean logic gate on the Si(001):H surface. AB - The design and construction of the first prototypical QHC (Quantum Hamiltonian Computing) atomic scale Boolean logic gate is reported using scanning tunnelling microscope (STM) tip-induced atom manipulation on an Si(001):H surface. The NOR/OR gate truth table was confirmed by dI/dU STS (Scanning Tunnelling Spectroscopy) tracking how the surface states of the QHC quantum circuit on the Si(001):H surface are shifted according to the input logical status. PMID- 26144213 TI - Reconfigurable assembly of superparamagnetic colloids confined in thermo reversible microtubes. AB - Structural transformations of superparamagnetic colloids confined within self assembled microtubes are studied by systematically varying tube-colloid size ratios and external magnetic field directions. A magnetic field parallel to microtubes may stretch non-linear chains like zigzag chains into linear chains. Non-parallel fields induce new structures including repulsive chains of single colloids, kinked chains and repulsive dimers, which are not observed for unconfined magnetic colloids in the bulk. The formed colloidal structures are confirmed via model calculations which account for tube-colloid size ratio effects and their reconfigurability with the field direction. Furthermore, structures are formed that allow controllable switching between a helical and a non-helical state. All observed field-induced transformations in microtubes are reversible provided the microtubes are not completely filled with colloids. In addition, we demonstrate magnetic field-responsive 2D crystallization by extending control over colloidal configurations in single microtubes to multiple well-aligned microtubes. PMID- 26144215 TI - A one-step carbonization route towards nitrogen-doped porous carbon hollow spheres with ultrahigh nitrogen content for CO2 adsorption. AB - Nitrogen doped porous carbon hollow spheres (N-PCHSs) with an ultrahigh nitrogen content of 15.9 wt% and a high surface area of 775 m(2) g(-1) were prepared using Melamine-formaldehyde nanospheres as hard templates and nitrogen sources. The N PCHSs were completely characterized and were found to exhibit considerable CO2 adsorption performance (4.42 mmol g(-1)). PMID- 26144214 TI - DDX3Y, a Male-Specific Region of Y Chromosome Gene, May Modulate Neuronal Differentiation. AB - Although it is apparent that chromosome complement mediates sexually dimorphic expression patterns of some proteins that lead to functional differences, there has been insufficient evidence following the manipulation of the male-specific region of the Y chromosome (MSY) gene expression during neural development. In this study, we profiled the expression of 23 MSY genes and 15 of their X-linked homologues during neural cell differentiation of NTERA-2 human embryonal carcinoma cell line (NT2) cells in three different developmental stages using qRT PCR, Western blotting, and immunofluorescence. The expression level of 12 Y linked genes significantly increased over neural differentiation, including RBMY1, EIF1AY, DDX3Y, HSFY1, BPY2, PCDH11Y, UTY, RPS4Y1, USP9Y, SRY, PRY, and ZFY. We showed that siRNA-mediated knockdown of DDX3Y, a DEAD box RNA helicase enzyme, in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after DDX3Y knockdown. Among 917 reproducibly identified proteins detected, 71 proteins were differentially expressed following DDX3Y siRNA treatment compared with mock treated cells. Functional grouping indicated that these proteins were involved in cell cycle, RNA splicing, and apoptosis, among other biological functions. Our results suggest that MSY genes may play an important role in neural differentiation and demonstrate that DDX3Y could play a multifunctional role in neural cell development, probably in a sexually dimorphic manner. PMID- 26144216 TI - Tunable water barrier properties of EVA by clay insertion? AB - Organo-modified Cloisite clays at varying contents were incorporated into poly(ethylene-co-vinyl acetate) (EVA) by melt blending. Nanoclay dispersion in films was first evaluated. The water transport properties were investigated by pervaporation and sorption measurements. A decrease of the water permeation flux was obtained when incorporating nanoparticles. This barrier effect is usually attributed to the increase of the diffusion pathways due to nanoclay-induced tortuosity effects. However, the diffusion coefficient was found to be dependent on water concentration, which generally reflects a plasticization effect of water. Besides, at 7 wt% of loading, an unexpected increase of water diffusivity was measured with a time-scale shift of the permeation flux. This was correlated with the formation of preferential diffusion pathways along interfacial regions due to free volumes existing between the EVA matrix and nanoclays as well as the water affinity of microfillers. As a consequence, water mass gain was found to be increased. The water-induced plasticization of sorbed water molecules was also highlighted through sorption kinetics. Eventually, some applications to these films in which water barrier behaviour is required were discussed. PMID- 26144217 TI - [(18)F]-NHC-BF3 adducts as water stable radio-prosthetic groups for PET imaging. AB - The radiofluorination of N-heterocyclic carbene (NHC) boron trifluoride adducts affords novel [(18)F]-positron emission tomography probes which resist hydrolytic fluoride release. The labelling protocol relies on an (18)F-(19)F isotopic exchange reaction promoted by the Lewis acid SnCl4. Modification of the NHC backbone with a maleimide functionality provides access to a model peptide conjugate which shows no evidence of defluorination when imaged in vivo. PMID- 26144218 TI - Noncovalent interactions determine the conformation of aurophilic complexes with 2-mercapto-4-methyl-5-thiazoleacetic acid ligands. AB - We report the synthesis of three gold(i) complexes [Au(H(2)-mmta)(2)]Cl.(3)H(2)O (1), Na(3)[Au(mmta)(2)].6H(2)O (2) and Na(3)[Au(mmta)(2)].10.5H(2)O (3) (H(2) mmta = 2-mercapto-4-methyl-5-thiazoleacetic acid) in which the Au(i) centre is incorporated either in cationic or anionic units of the [Au(SR)(2)](+/-) type depending on the protonation state of the ligand. All structures were characterized by single crystal X-ray analysis and found to exhibit unsupported aurophilic interactions leading to the formation of dimeric [Au(2)(H(2) mmta)(4)](2+) and [Au(2)(mmta)(4)](6-) species. By applying several ab initio interpretative techniques we examine the character of the intermolecular interactions stabilizing the eclipsed arrangement of the aurophilic dimers formed in 1-3. PMID- 26144219 TI - A cryo-generated ferrous-superoxo porphyrin: EPR, resonance Raman and DFT studies. AB - The resonance Raman analysis of cryo-generated ferrous-superoxy heme has been performed for the first time, and its structure and the reaction mechanism are rationalized by DFT calculations. The presence of another electronic tautomer of ferrous-superoxy heme is predicted computationally. PMID- 26144220 TI - Intrinsic defects in a photovoltaic perovskite variant Cs2SnI6. AB - Cs2SnI6, a rarely studied perovskite variant material, is recently gaining a lot of interest in the field of photovoltaics owing to its nontoxicity, air-stability and promising photovoltaic properties. In this work, we report intrinsic defects in Cs2SnI6 using first-principles density functional theory calculations. It is revealed that iodine vacancy and tin interstitial are the dominant defects that are responsible for the intrinsic n-type conduction in Cs2SnI6. Tin vacancy has a very high formation energy (>3.6 eV) due to the strong covalency in the Sn-I bonds and is hardly generated for p-type doping. All the dominant defects in Cs2SnI6 have deep transition levels in the band gap. It is suggested that the formation of deep defects can be suppressed significantly by employing an I-rich synthesis condition, which is inevitable for photovoltaic and other semiconductor applications. PMID- 26144221 TI - Three-Dimensional Rapid Prototyping of Multidirectional Polymer Nanoprobes for Single Cell Insertion. AB - Three-dimensional (3D) thermal drawing at nanoscale as a novel rapid prototyping method was demonstrated to create multidirectional polymer nanoprobes for single cell analysis. This 3D drawing enables simple and rapid fabrication of polymeric nanostructures with high aspect ratio. The effect of thermal drawing parameters, such as drawing speeds, dipping depths, and contact duration on the final geometry of polymer nanostructures was investigated. Vertically aligned and L shaped nanoprobes were fabricated and their insertion into living single cells such as algal cells and human neural stem cells was demonstrated. This technique can be extended to create more complex 3D structures by controlling drawing steps and directions on any surface. PMID- 26144222 TI - Behavior of Supported Palladium Oxide Nanoparticles under Reaction Conditions, Studied with near Ambient Pressure XPS. AB - Near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) is a promising method to close the "pressure gap", and thus, study the surface composition during heterogeneous reactions in situ. The specialized spectrometers necessary for this analytical technique have recently been adapted to operate with a conventional X-ray source, making it available for routine quantitative analysis in the laboratory. This is shown in the present in situ study of the partial oxidation of 2-propanol catalyzed with PdO nanoparticles supported on TiO2, which was investigated under reaction conditions as a function of gas composition (alcohol-to-oxygen ratio) and temperature. Exposure of the nanoparticles to 2 propanol at 30 degrees C leads to immediate partial reduction of the PdO, followed by a continuous reduction of the remaining PdO during heating. However, gaseous oxygen inhibits the reduction of PdO below 90 degrees C, and the oxidation of 2-propanol to carboxylates only occurs in the presence of oxygen above 90 degrees C. These results support the theory that metallic palladium is the active catalyst material, and they show that environmental conditions affect the nanoparticles and the reaction process significantly. The study also revealed challenges and limitations of this analytical method. Specifically, the intensity and fixed photon energy of a conventional X-ray source limit the spectral resolution and surface sensitivity of lab-based NAP-XPS, which affect precision and accuracy of the quantitative analysis. PMID- 26144223 TI - Introduction to selected articles from the 15th ICCBM. PMID- 26144224 TI - Trace fluorescent labeling for protein crystallization. AB - Fluorescence can be a powerful tool to aid in the crystallization of proteins. In the trace-labeling approach, the protein is covalently derivatized with a high quantum-yield visible-wavelength fluorescent probe. The final probe concentration typically labels <=0.20% of the protein molecules, which has been shown to not affect the crystal nucleation or diffraction quality. The labeled protein is then used in a plate-screening experiment in the usual manner. As the most densely packed state of the protein is the crystalline form, then crystals show as the brightest objects in the well under fluorescent illumination. A study has been carried out on the effects of trace fluorescent labeling on the screening results obtained compared with nonlabeled protein, and it was found that considering the stochastic nature of the crystal nucleation process the presence of the probe did not affect the outcomes obtained. Other effects are realised when using fluorescence. Crystals are clearly seen even when buried in precipitate. This approach also finds 'hidden' leads, in the form of bright spots, with ~30% of the leads found being optimized to crystals in a single-pass optimization trial. The use of visible fluorescence also enables the selection of colors that bypass interfering substances, and the screening materials do not have to be UV transparent. PMID- 26144225 TI - Do protein crystals nucleate within dense liquid clusters? AB - Protein-dense liquid clusters are regions of high protein concentration that have been observed in solutions of several proteins. The typical cluster size varies from several tens to several hundreds of nanometres and their volume fraction remains below 10(-3) of the solution. According to the two-step mechanism of nucleation, the protein-rich clusters serve as locations for and precursors to the nucleation of protein crystals. While the two-step mechanism explained several unusual features of protein crystal nucleation kinetics, a direct observation of its validity for protein crystals has been lacking. Here, two independent observations of crystal nucleation with the proteins lysozyme and glucose isomerase are discussed. Firstly, the evolutions of the protein-rich clusters and nucleating crystals were characterized simultaneously by dynamic light scattering (DLS) and confocal depolarized dynamic light scattering (cDDLS), respectively. It is demonstrated that protein crystals appear following a significant delay after cluster formation. The cDDLS correlation functions follow a Gaussian decay, indicative of nondiffusive motion. A possible explanation is that the crystals are contained inside large clusters and are driven by the elasticity of the cluster surface. Secondly, depolarized oblique illumination dark-field microscopy reveals the evolution from liquid clusters without crystals to newly nucleated crystals contained in the clusters to grown crystals freely diffusing in the solution. Collectively, the observations indicate that the protein-rich clusters in lysozyme and glucose isomerase solutions are locations for crystal nucleation. PMID- 26144226 TI - Towards time-resolved serial crystallography in a microfluidic device. AB - Serial methods for crystallography have the potential to enable dynamic structural studies of protein targets that have been resistant to single-crystal strategies. The use of serial data-collection strategies can circumvent challenges associated with radiation damage and repeated reaction initiation. This work utilizes a microfluidic crystallization platform for the serial time resolved Laue diffraction analysis of macroscopic crystals of photoactive yellow protein (PYP). Reaction initiation was achieved via pulsed laser illumination, and the resultant electron-density difference maps clearly depict the expected pR(1)/pR(E46Q) and pR(2)/pR(CW) states at 10 us and the pB1 intermediate at 1 ms. The strategies presented here have tremendous potential for extension to chemical triggering methods for reaction initiation and for extension to dynamic, multivariable analyses. PMID- 26144227 TI - The MORPHEUS II protein crystallization screen. AB - High-quality macromolecular crystals are a prerequisite for the process of protein structure determination by X-ray diffraction. Unfortunately, the relative yield of diffraction-quality crystals from crystallization experiments is often very low. In this context, innovative crystallization screen formulations are continuously being developed. In the past, MORPHEUS, a screen in which each condition integrates a mix of additives selected from the Protein Data Bank, a cryoprotectant and a buffer system, was developed. Here, MORPHEUS II, a follow-up to the original 96-condition initial screen, is described. Reagents were selected to yield crystals when none might be observed in traditional initial screens. Besides, the screen includes heavy atoms for experimental phasing and small polyols to ensure the cryoprotection of crystals. The suitability of the resulting novel conditions is shown by the crystallization of a broad variety of protein samples and their efficiency is compared with commercially available conditions. PMID- 26144228 TI - Use of dynamic light scattering and small-angle X-ray scattering to characterize new surfactants in solution conditions for membrane-protein crystallization. AB - The structural and interactive properties of two novel hemifluorinated surfactants, F2H9-beta-M and F4H5-beta-M, the syntheses of which were based on the structure and hydrophobicity of the well known dodecyl-beta-maltoside (DD beta-M), are described. The shape of their micellar assemblies was characterized by small-angle X-ray scattering and their intermicellar interactions in crystallizing conditions were measured by dynamic light scattering. Such information is essential for surfactant phase-diagram determination and membrane protein crystallization. PMID- 26144229 TI - Crystallographic analysis of a novel aldo-keto reductase from Thermotoga maritima in complex with NADP+. AB - Aldo-keto reductases (AKRs) are a superfamily of NAD(P)H-dependent oxidoreductases that catalyse the asymmetric reduction of aldehydes and ketones to chiral alcohols in various organisms. The novel aldo-keto reductase Tm1743 from Thermotoga maritima was identified to have a broad substrate specificity and high thermostability, serving as an important enzyme in biocatalysis and fine chemical synthesis. In this study, Tm1743 was overexpressed in Escherichia coli BL21(DE3) cells with an N-terminal His6 tag and was purified by Ni(2+)-chelating affinity and size-exclusion chromatography. Purified recombinant enzyme was incubated with its cofactor NADP(+) and its substrate ethyl 2-oxo-4 phenylbutyrate (EOPB) for crystallization. Two X-ray diffraction data sets were collected at 2.0 and 1.7 A resolution from dodecahedral crystals grown from samples containing Tm1743-NADP(+)-EOPB and Tm1743-NADP(+), respectively. Both crystals belonged to space group P3121, with similar unit-cell parameters. However, in the refined structure model only NADP(+) was observed in the active site of the full-length Tm1743 enzyme. Degradation of the N-terminal vector derived amino acids during crystallization was confirmed by Western blot and mass spectrometric analyses. PMID- 26144230 TI - Batch crystallization of rhodopsin for structural dynamics using an X-ray free electron laser. AB - Rhodopsin is a membrane protein from the G protein-coupled receptor family. Together with its ligand retinal, it forms the visual pigment responsible for night vision. In order to perform ultrafast dynamics studies, a time-resolved serial femtosecond crystallography method is required owing to the nonreversible activation of rhodopsin. In such an approach, microcrystals in suspension are delivered into the X-ray pulses of an X-ray free-electron laser (XFEL) after a precise photoactivation delay. Here, a millilitre batch production of high density microcrystals was developed by four methodical conversion steps starting from known vapour-diffusion crystallization protocols: (i) screening the low-salt crystallization conditions preferred for serial crystallography by vapour diffusion, (ii) optimization of batch crystallization, (iii) testing the crystal size and quality using second-harmonic generation (SHG) imaging and X-ray powder diffraction and (iv) production of millilitres of rhodopsin crystal suspension in batches for serial crystallography tests; these crystals diffracted at an XFEL at the Linac Coherent Light Source using a liquid-jet setup. PMID- 26144232 TI - Crystallographic analysis of the Arabidopsis thaliana BAG5-calmodulin protein complex. AB - Arabidopsis thaliana BAG5 (AtBAG5) belongs to the plant BAG (Bcl-2-associated athanogene) family that performs diverse functions ranging from growth and development to abiotic stress and senescence. BAG family members can act as nucleotide-exchange factors for heat-shock protein 70 (Hsp70) through binding of their evolutionarily conserved BAG domains to the Hsp70 ATPase domain, and thus may be involved in the regulation of chaperone-mediated protein folding in plants. AtBAG5 is distinguished from other family members by the presence of a unique IQ motif adjacent to the BAG domain; this motif is specific for calmodulin (CaM) binding, indicating a potential role in the plant calcium signalling pathway. To provide a better understanding of the IQ motif-mediated interaction between AtBAG5 and CaM, the two proteins were expressed and purified separately and then co-crystallized together. Diffraction-quality crystals of the complex were grown using the sitting-drop vapour-diffusion technique from a condition consisting of 0.1 M Tris-HCl pH 8.5, 2.5 M ammonium sulfate. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 64.56, b = 74.89, c = 117.09 A. X-ray diffraction data were recorded to a resolution of 2.5 A from a single crystal using synchrotron radiation. Assuming the presence of two molecules in the asymmetric unit, a Matthews coefficient of 2.44 A(3) Da(-1) was calculated, corresponding to a solvent content of approximately 50%. PMID- 26144231 TI - Fusion-protein-assisted protein crystallization. AB - Fusion proteins can be used directly in protein crystallization to assist crystallization in at least two different ways. In one approach, the 'heterologous fusion-protein approach', the fusion partner can provide additional surface area to promote crystal contact formation. In another approach, the 'fusion of interacting proteins approach', protein assemblies can be stabilized by covalently linking the interacting partners. The linker connecting the proteins plays different roles in the two applications: in the first approach a rigid linker is required to reduce conformational heterogeneity; in the second, conversely, a flexible linker is required that allows the native interaction between the fused proteins. The two approaches can also be combined. The recent applications of fusion-protein technology in protein crystallization from the work of our own and other laboratories are briefly reviewed. PMID- 26144233 TI - Structural characterization of the principal mRNA-export factor Mex67-Mtr2 from Chaetomium thermophilum. AB - Members of the Mex67-Mtr2/NXF-NXT1 family are the principal mediators of the nuclear export of mRNA. Mex67/NXF1 has a modular structure based on four domains (RRM, LRR, NTF2-like and UBA) that are thought to be present across species, although the level of sequence conservation between organisms, especially in lower eukaryotes, is low. Here, the crystal structures of these domains from the thermophilic fungus Chaetomium thermophilum are presented together with small angle X-ray scattering (SAXS) and in vitro RNA-binding data that indicate that, not withstanding the limited sequence conservation between different NXF family members, the molecules retain similar structural and RNA-binding properties. Moreover, the resolution of crystal structures obtained with the C. thermophilum domains was often higher than that obtained previously and, when combined with solution and biochemical studies, provided insight into the structural organization, self-association and RNA-binding properties of Mex67-Mtr2 that facilitate mRNA nuclear export. PMID- 26144234 TI - Expression, purification, crystallization and crystallographic study of the Aspergillus terreus aromatic prenyltransferase AtaPT. AB - Prenylated aromatics are produced by aromatic prenyltransferases during the secondary metabolism of bacteria, fungi and plants. The prenylation of nonprenylated precursors can lead to great chemical diversity and extensive biological properties. Aspergillus terreus aromatic prenyltransferase (AtaPT), which has recently been discovered and characterized, is such an enzyme and is responsible for the prenylation of various aromatic compounds. Here, recombinant AtaPT was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to a resolution of 1.71 A and the crystal belonged to space group P2(1)2(1)2, with unit-cell parameters a = 96.2, b = 135.8, c = 69.5 A, alpha = beta = gamma = 90 degrees . Analysis of the calculated Matthews coefficient and the self-rotation function suggested that there are two AtaPT molecules in the asymmetric unit. PMID- 26144235 TI - Structure of human saposin A at lysosomal pH. AB - The saposins are essential cofactors for the normal lysosomal degradation of complex glycosphingolipids by acid hydrolase enzymes; defects in either saposin or hydrolase function lead to severe metabolic diseases. Saposin A (SapA) activates the enzyme beta-galactocerebrosidase (GALC), which catalyzes the breakdown of beta-D-galactocerebroside, the principal lipid component of myelin. SapA is known to bind lipids and detergents in a pH-dependent manner; this is accompanied by a striking transition from a 'closed' to an 'open' conformation. However, previous structures were determined at non-lysosomal pH. This work describes a 1.8 A resolution X-ray crystal structure determined at the physiologically relevant lysosomal pH 4.8. In the absence of lipid or detergent at pH 4.8, SapA is observeed to adopt a conformation closely resembling the previously determined 'closed' conformation, showing that pH alone is not sufficient for the transition to the 'open' conformation. Structural alignments reveal small conformational changes, highlighting regions of flexibility. PMID- 26144236 TI - Synthesis, purification and crystallographic studies of the C-terminal sterol carrier protein type 2 (SCP-2) domain of human hydroxysteroid dehydrogenase-like protein 2. AB - Human hydroxysteroid dehydrogenase-like protein 2 (HSDL2) is a member of the short-chain dehydrogenase/reductase (SDR) subfamily of oxidoreductases and contains an N-terminal catalytic domain and a C-termianl sterol carrier protein type 2 (SCP-2) domain. In this study, the C-terminal SCP-2 domain of human HSDL2, including residues Lys318-Arg416, was produced in Escherichia coli, purified and crystallized. X-ray diffraction data were collected to 2.10 A resolution. The crystal belonged to the trigonal space group P3(1)21 (or P3(2)21), with unit-cell parameters a = b = 70.4, c = 60.6 A, alpha = beta = 90, gamma = 120 degrees . Two protein molecules are present in the asymmetric unit, resulting in a Matthews coefficient of 2.16 A(3) Da(-1) and an approximate solvent content of 43%. PMID- 26144237 TI - The structure of nerve growth factor in complex with lysophosphatidylinositol. AB - Nerve growth factor (NGF) is an important protein that is involved in a variety of physiological processes in cell survival, differentiation, proliferation and maintenance. The previously reported crystal structure of mouse NGF (mNGF) in complex with lysophosphatidylserine (LysoPS) showed that mNGF can bind LysoPS at its dimeric interface. To expand the understanding of the structural basis for specific lipid recognition by NGF, the crystal structure of mNGF complexed with lysophosphatidylinositol (13:0 LysoPI) was solved. Interestingly, in addition to Lys88, which interacts with the head glycerol group and the phosphate group of LysoPI, as seen in the mNGF-LysoPS structure, two additional residues, Tyr52 and Arg50, were found to assist in lipid binding by forming hydrogen bonds to the inositol moiety of the LysoPI molecule. The results suggest a specific recognition mechanism of inositol group-containing lipids by NGF, which may help in the design of bioactive compounds that can be delivered by NGF. PMID- 26144238 TI - The structure of a GFP-based antibody (fluorobody) to TLH, a toxin from Vibrio parahaemolyticus. AB - A fluorobody is a manmade hybrid molecule that is composed of green fluorescent protein (GFP) and a fragment of antibody, which combines the affinity and specificity of an antibody with the visibility of a GFP. It is able to provide a real-time indication of binding while avoiding the use of tags and secondary binding reagents. Here, the expression, purification and crystal structure of a recombinant fluorobody for TLH (thermolabile haemolysin), a toxin from the lethal food-borne disease bacterium Vibrio parahaemolyticus, are presented. This is the first structure of a fluorobody to be reported. Crystals belonging to space group P4(3)2(1)2, with unit-cell parameters a = b = 63.35, c = 125.90 A, were obtained by vapour diffusion in hanging drops and the structure was refined to an Rfree of 16.7% at 1.5 A resolution. The structure shows a CDR loop of the antibody on the GFP scaffold. PMID- 26144239 TI - The crystal and solution structure of YdiE from Escherichia coli. AB - Iron-containing porphyrins are essential for all life as electron carriers. Since iron is poorly available in an oxidizing environment, bacterial growth may be restricted by iron limitation, and this has led to the evolution of a huge variety of iron-uptake systems. Among pathogens, iron scavenging from the haemoglobin of an animal host is a common means of acquiring sufficient iron for growth. The Isd system of Staphylococcus aureus is a well studied example; the bacterium devotes considerable resources to the construction of surface proteins that deftly remove haem from haemoglobin and pass it along a chain of related proteins, eventually delivering the haem to the cytoplasm, where it can be utilized or degraded. All organisms, however, must deal with haem and related molecules, which are by their nature hydrophobic and prone to precipitate, and which tend to promote the formation of reactive oxygen species. Chaperones are an obvious solution to the problem of maintaining a pool of haem for insertion into cytochromes without allowing naked haem to cause damage. YdiE is a very small protein from Escherichia coli of only 63 residues which may play a role in haem trafficking. Here, NMR analysis and the crystal structure of the protein to high resolution are reported. PMID- 26144240 TI - Expression, purification, crystallization and crystallographic study of Lutzomyia longipalpis LJL143. AB - Leishmaniasis is a neglected vector-borne disease with a global prevalence of over 12 million cases and 59,000 annual deaths. Transmission of the parasite requires salivary proteins, including LJL143 from the New World sandfly Lutzomyia longipalpis. LJL143 is a known marker of sandfly exposure in zoonotic hosts. LJL143 was crystallized from soluble protein expressed using Pichia pastoris. X ray data were collected to 2.6 A resolution from orthorhombic crystals belonging to space group P2(1)2(1)2(1), with average unit-cell parameters a = 57.39, b = 70.24, c = 79.58 A. The crystals are predicted to have a monomer in the asymmetric unit, with an estimated solvent content of 48.5%. LJL143 has negligible homology to any reported structures, so the phases could not be determined by molecular replacement. All attempts at S-SAD failed and future studies include experimental phase determination using heavy-atom derivatives. PMID- 26144241 TI - Management of polysensitized patient: from molecular diagnostics to biomolecular immunotherapy. AB - A panel of Italian allergists gathered to discuss the issue concerning the management of polysensitized patients. The main conclusions were as follows: polysensitization is a relevant clinical characteristic as it affects about 70 80% of the global allergic population; the diagnostic pathway needs the use of an adequate and thorough methodology, based on the demonstration of consistency between history and documented sensitization; polysensitization and polyallergy are not synonymous: true allergy should always be demonstrated; polysensitization does not constitute a limitation to allergen immunotherapy prescription, as 1-2 allergen extracts could be effective in polysensitized patients; the allergen immunotherapy product characteristics should include the following: high efficacy and optimal safety profile, standardized production, and documented presence and titration of the major allergen. PMID- 26144242 TI - Tip-Directed Synthesis of Multimetallic Nanoparticles. AB - Alloy nanoparticles are important in many fields, including catalysis, plasmonics, and electronics, due to the chemical and physical properties that arise from the interactions between their components. Typically, alloy nanoparticles are made by solution-based synthesis; however, scanning-probe-based methods offer the ability to make and position such structures on surfaces with nanometer-scale resolution. In particular, scanning probe block copolymer lithography (SPBCL), which combines elements of block copolymer lithography with scanning probe techniques, allows one to synthesize nanoparticles with control over particle diameter in the 2-50 nm range. Thus far, single-element structures have been studied in detail, but, in principle, one could make a wide variety of multicomponent systems by controlling the composition of the polymer ink, polymer feature size, and metal precursor concentrations. Indeed, it is possible to use this approach to synthesize alloy nanoparticles comprised of combinations of Au, Ag, Pd, Ni, Co, and Pt. Here, such structures have been made with diameters deliberately tailored in the 10-20 nm range and characterized by STEM and EDS for structural and elemental composition. The catalytic activity of one class of AuPd alloy nanoparticles made via this method was evaluated with respect to the reduction of 4-nitrophenol with NaBH4. In addition to being the first catalytic studies of particles made by SPBCL, these proof-of-concept experiments demonstrate the potential for SPBCL as a new method for studying the fundamental science and potential applications of alloy nanoparticles in areas such as heterogeneous catalysis. PMID- 26144243 TI - Analysis of audiological results of patients referred from newborn hearing screening program. AB - CONCLUSION: As tools of confirmation of sensorineural hearing loss in neonates who are 'referred' from a newborn hearing screening program, both ASSR and DPOAE have high sensitivity and specificity. In addition, ASSR can be used as a substitute for ABR. OBJECTIVES: To analyze the confirmative audiological results of patients referred from a newborn hearing screening program. PATIENTS AND METHOD: From January 2007 to December 2013, hearing tests were performed on 474 babies (804 ears) who were 'referred' from the hospital or other maternity centers. Auditory brainstem response (ABR), auditory steady-state response (ASSR), and distortion product otoacoustic emissions (DPOAE) were used for hearing evaluation. RESULTS: Of 474 babies (804 ears), 232 had normal hearing, while 242 babies (358 ears) had over 30 dB nHL threshold from ABR. Among the 156 babies (312 ears) who underwent both ABR and ASSR, the mean ASSR threshold had a strong correlation with ABR threshold (r = 0.942, p < 0.001). Assuming that ABR results were the yardstick of abnormal hearing, sensitivity and specificity of ASSR to ABR were 90.6% and 95%. DPOAE tests were performed on 180 babies (360 ears), with sensitivity of 85.9% and specificity of 84.4%. PMID- 26144244 TI - Interactions between working memory and language in young children with specific language impairment (SLI). AB - The underlying structure of working memory (WM) in young children with and without specific language impairment (SLI) was examined. The associations between the components of WM and the language abilities of young children with SLI were then analyzed. The Automated Working Memory Assessment and four linguistic tasks were administered to 58 children with SLI and 58 children without SLI, aged 4-5 years. The WM of the children was best represented by a model with four separate but interacting components of verbal storage, visuospatial storage, verbal central executive (CE), and visuospatial CE. The associations between the four components of WM did not differ significantly for the two groups of children. However, the individual components of WM showed varying associations with the language abilities of the children with SLI. The verbal CE component of WM was moderately to strongly associated with all the language abilities in children with SLI: receptive vocabulary, expressive vocabulary, verbal comprehension, and syntactic development. These results show verbal CE to be involved in a wide range of linguistic skills; the limited ability of young children with SLI to simultaneously store and process verbal information may constrain their acquisition of linguistic skills. Attention should thus be paid to the language problems of children with SLI, but also to the WM impairments that can contribute to their language problems. PMID- 26144245 TI - Predicting the incidence of hand, foot and mouth disease in Sichuan province, China using the ARIMA model - CORRIGENDUM. PMID- 26144247 TI - Limits Of Quantum Information In Weak Interaction Processes Of Hyperons. AB - We analyze the achievable limits of the quantum information processing of the weak interaction revealed by hyperons with spin. We find that the weak decay process corresponds to an interferometric device with a fixed visibility and fixed phase difference for each hyperon. Nature chooses rather low visibilities expressing a preference to parity conserving or violating processes (except for the decay Sigma(+)-> ppi(0)). The decay process can be considered as an open quantum channel that carries the information of the hyperon spin to the angular distribution of the momentum of the daughter particles. We find a simple geometrical information theoretic interpretation of this process: two quantization axes are chosen spontaneously with probabilities where alpha is proportional to the visibility times the real part of the phase shift. Differently stated, the weak interaction process corresponds to spin measurements with an imperfect Stern-Gerlach apparatus. Equipped with this information theoretic insight we show how entanglement can be measured in these systems and why Bell's nonlocality (in contradiction to common misconception in literature) cannot be revealed in hyperon decays. Last but not least we study under which circumstances contextuality can be revealed. PMID- 26144248 TI - Motif analysis in directed ordered networks and applications to food webs. AB - The analysis of small recurrent substructures, so called network motifs, has become a standard tool of complex network science to unveil the design principles underlying the structure of empirical networks. In many natural systems network nodes are associated with an intrinsic property according to which they can be ordered and compared against each other. Here, we expand standard motif analysis to be able to capture the hierarchical structure in such ordered networks. Our new approach is based on the identification of all ordered 3-node substructures and the visualization of their significance profile. We present a technique to calculate the fine grained motif spectrum by resolving the individual members of isomorphism classes (sets of substructures formed by permuting node-order). We apply this technique to computer generated ensembles of ordered networks and to empirical food web data, demonstrating the importance of considering node order for food-web analysis. Our approach may not only be helpful to identify hierarchical patterns in empirical food webs and other natural networks, it may also provide the base for extending motif analysis to other types of multi layered networks. PMID- 26144249 TI - Single Mode ZnO Whispering-Gallery Submicron Cavity and Graphene Improved Lasing Performance. AB - Single-mode ultraviolet (UV) laser of ZnO is still in challenge so far, although it has been paid great attention along the past decades. In this work, single mode lasing resonance was realized in a submicron-sized ZnO rod based on serially varying the dimension of the whispering-gallery mode (WGM) cavities. The lasing performance, such as the lasing quality factor (Q) and the lasing intensity, was remarkably improved by facilely covering monolayer graphene on the ZnO submicron rod. The mode structure evolution from multimodes to single-mode was investigated systematically based on the total internal-wall reflection of the ZnO microcavities. Graphene-induced optical field confinement and lasing emission enhancement were revealed, indicating an energy coupling between graphene SP and ZnO exciton emission. This result demonstrated the response of graphene in the UV wavelength region and extended its potential applications besides many previous reports on the multifunctional graphene/semiconductor hybrid materials and devices in advanced electronics and optoelectronics areas. PMID- 26144251 TI - Getting over our Immune-Complex - C5a receptor blockade is the answer. PMID- 26144250 TI - Activation of TLR7 increases CCND3 expression via the downregulation of miR-15b in B cells of systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell hyperreactivity. The Toll-like receptor 7 (TLR7) signaling pathway is abnormally activated in SLE B cells. CyclinD3 (CCND3) plays an important role in B-cell proliferation, development, and differentiation. Although previous studies focused on the B cell-intrinsic role of TLR7 for the development of spontaneous germinal centers, the influence of TLR7 on CCND3 in SLE B cells is still not clear. Here, we used a B-cell profiling chip and found that CCND3 was related to SLE and significantly elevated in SLE B cells. Moreover, we determined that the expression level of CCND3 was higher, while miR-15b was significantly lower in the B cells from SLE patients and B6.MRL-Faslpr/J lupus mice compared to normal subjects. Furthermore, we demonstrated that the activation of TLR7 dramatically increased CCND3 expression but significantly decreased miR-15b in B cells in vitro and we identified that CCND3 is a direct target of miR-15b. To further confirm our results, we established another lupus model by topically treating C57BL/6 (B6) mice with the TLR-7 agonist imiquimod (IMQ) for 8 weeks according to the previously described protocol. Expectedly, topical treatment with IMQ also significantly increased CCND3 and decreased miR-15b in B cells of B6 mice. Taken together, our results identified that the activation of TLR7 increased CCND3 expression via the downregulation of miR-15b in B cells; thus, these findings suggest that extrinsic factor-induced CCND3 expression may contribute to the abnormality of B cell in SLE. PMID- 26144252 TI - Pilot study of adoptive immunotherapy with sentinel node-derived T cells in muscle-invasive urinary bladder cancer. AB - OBJECTIVE: The aim of this study was to determine by computed tomography (CT) whether treatment with tumor-draining lymph-node-derived expanded autologous T lymphocytes results in objective responses and/or improved survival in patients with metastatic urinary bladder cancer (UBC) and to record the toxicity of the treatment. MATERIALS AND METHODS: Eighteen patients with metastatic UBC were prospectively selected from two centers. The preoperative staging was T2-T4bN1-2 and/or M0-M1 or MX. Tumor-draining lymph nodes were harvested at intended cystectomy for the extraction of T lymphocytes. This was followed by expansion of the T lymphocytes in a cell culture, and subsequent reinfusion of these autologous tumor-specific T lymphocytes. Responses to therapy were evaluated by CT scans according to Response Evaluation Criteria In Solid Tumors (RECIST) and clinical follow-up, according to the research protocol. RESULTS: Nine out of 18 patients were treated. Treatment was feasible and safe. In two out of nine immunologically treated patients, objective responses were detected in terms of diminished or obliterated nodal metastases. When excluding three patients with disseminated osseous metastases plus one with a T4b tumor left in situ, a success rate of two out of six treated patients was seen. The two responders had survival times of 35 and 11 months, respectively. No toxicity was recorded. CONCLUSIONS: Infusion of expanded autologous tumor-specific T lymphocytes is feasible and safe, and objective responses according to RECIST were recorded. One objective responder to immunotherapy displayed notably long overall survival. PMID- 26144254 TI - SiNG-PCRseq: Accurate inter-sequence quantification achieved by spiking-in a neighbor genome for competitive PCR amplicon sequencing. AB - Despite the recent technological advances in DNA quantitation by sequencing, accurate delineation of the quantitative relationship among different DNA sequences is yet to be elaborated due to difficulties in correcting the sequence specific quantitation biases. We here developed a novel DNA quantitation method via spiking-in a neighbor genome for competitive PCR amplicon sequencing (SiNG PCRseq). This method utilizes genome-wide chemically equivalent but easily discriminable homologous sequences with a known copy arrangement in the neighbor genome. By comparing the amounts of selected human DNA sequences simultaneously to those of matched sequences in the orangutan genome, we could accurately draw the quantitative relationships for those sequences in the human genome (root-mean square deviations <0.05). Technical replications of cDNA quantitation performed using different reagents at different time points also resulted in excellent correlations (R(2) > 0.95). The cDNA quantitation using SiNG-PCRseq was highly concordant with the RNA-seq-derived version in inter-sample comparisons (R(2) = 0.88), but relatively discordant in inter-sequence quantitation (R(2) < 0.44), indicating considerable level of sequence-dependent quantitative biases in RNA seq. Considering the measurement structure explicitly relating the amount of different sequences within a sample, SiNG-PCRseq will facilitate sharing and comparing the quantitation data generated under different spatio-temporal settings. PMID- 26144253 TI - Cryo-EM structure of the bacteriophage T4 portal protein assembly at near-atomic resolution. AB - The structure and assembly of bacteriophage T4 has been extensively studied. However, the detailed structure of the portal protein remained unknown. Here we report the structure of the bacteriophage T4 portal assembly, gene product 20 (gp20), determined by cryo-electron microscopy (cryo-EM) to 3.6 A resolution. In addition, analysis of a 10 A resolution cryo-EM map of an empty prolate T4 head shows how the dodecameric portal assembly interacts with the capsid protein gp23 at the special pentameric vertex. The gp20 structure also verifies that the portal assembly is required for initiating head assembly, for attachment of the packaging motor, and for participation in DNA packaging. Comparison of the Myoviridae T4 portal structure with the known portal structures of phi29, SPP1 and P22, representing Podo- and Siphoviridae, shows that the portal structure probably dates back to a time when self-replicating microorganisms were being established on Earth. PMID- 26144256 TI - A genetic analysis of the Italian Salernitano horse. AB - Salernitano (SAL) is an ancient Italian horse breed developed over the course of the ages together with Napoletano and, during the 20th century, by crossing with Thoroughbred horse lines. Excellent in hurdle jumping, this breed is currently facing a concrete risk of extinction due to the lack of appropriate management strategies. This research is the first SAL genetic characterization that aims to set up the basic knowledge for a conservation plan. A representative sample of 61 SALs was analyzed by means of a set of 16 microsatellites markers (short tandem repeats (STRs)). The sequence of hypervariable D-loop mtDNA region was also performed on a subset of 24 mares in order to study the maternal diversity and obtain a complete picture of the internal genetic variation. All the molecular data were analyzed together with those obtained from three Sicilian horse breeds investigated in a previous research (Siciliano, Sanfratellano and Sicilian Oriental Purebred). STRs markers revealed a moderate level of genetic diversity in SAL (alleles/locus 5.1, He 0.67) and confirmed the hunch of genetic erosion. Autosomal variability highlighted a very light deficit of homozygotes (FIS= 0.067). Experimental D-loop sequences were compared by multiple alignments with those retrieved from biological databases and revealed two unreported haplotypes. The phylogenetic network, which was built on mtDNA sequences, included various cosmopolitan and European horses and showed SAL haplotypes distributed among different mtDNA lineages. PMID- 26144257 TI - Erratum: Prospective randomized comparison of gastrotomy closure associating tunnel access and over-the-scope clip (OTSC) with two other methods in an experimental ex vivo setting. AB - [This corrects the article DOI: 10.1055/s-0034-1390794.]. PMID- 26144255 TI - The circadian clock rephases during lateral root organ initiation in Arabidopsis thaliana. AB - The endogenous circadian clock enables organisms to adapt their growth and development to environmental changes. Here we describe how the circadian clock is employed to coordinate responses to the key signal auxin during lateral root (LR) emergence. In the model plant, Arabidopsis thaliana, LRs originate from a group of stem cells deep within the root, necessitating that new organs emerge through overlying root tissues. We report that the circadian clock is rephased during LR development. Metabolite and transcript profiling revealed that the circadian clock controls the levels of auxin and auxin-related genes including the auxin response repressor IAA14 and auxin oxidase AtDAO2. Plants lacking or overexpressing core clock components exhibit LR emergence defects. We conclude that the circadian clock acts to gate auxin signalling during LR development to facilitate organ emergence. PMID- 26144258 TI - Finding the right approach to big data-driven medicinal chemistry. PMID- 26144259 TI - Nicotine for psychiatric disease: from nuisance to novel treatment? PMID- 26144260 TI - Photodynamic inactivation of bacteria: finding the effective targets. PMID- 26144261 TI - A potential tailor-made hyaluronic acid buccal delivery system comprising rotigotine for Parkinson's disease? AB - AIMS: Parkinson's disease (PD) affects over 10 million people around the world. Dysphagia is one of its main problems. Therefore, mucosal delivery is beneficial for patient compliance. This study aimed to synthesize mucoadhesive hyaluronic acid (HA) comprising rotigotine for the treatment of PD. MATERIALS & METHODS: HA a biocompatible, naturally occurring polysaccharide - was chemically modified with the thiol-bearing ligand cysteine ethyl ester via amide bond formation (HAC). HAC was evaluated in terms of stability, cytotoxicity, permeation enhancement, controlled drug release and mucoadhesiveness. RESULTS: HAC showed 1.49-fold higher stability, 3.47-fold improved swelling capacity and 12.16-fold augmentation in mucoadhesion. Additionally, HAC exhibited 1.18-fold permeation enhancement over HA. DISCUSSION: Taking the findings into consideration, HAC represents a pillar of mucosal buccal delivery in the treatment of PD. PMID- 26144262 TI - Organogermanium compound, Ge-132, forms complexes with adrenaline, ATP and other physiological cis-diol compounds. AB - BACKGROUND: In mammals, adrenaline and ATP are life-essential vicinal diol and cis-diol functional groups. Here, we show that interactions between a safe organogermanium compound and these cis-diol compounds have the potential to regulate physiological functions. In addition, we represent a possible new druggable target for controlling the action of cis-diol compounds. RESULTS: We analyzed a single crystal structure of organogermanium 3 (trihydroxygermyl)propanoic acid (THGPA), a hydrolysate of safe Ge-132, in complex with catecholamine (adrenaline and noradrenaline), and evaluated the affinity between several cis-diol compounds and THGPA by NMR. An in vitro study using normal human epidermal keratinocytes was performed to investigate the inhibition of cis-diol compound-stimulated receptors by THGPA. At high concentration, THGPA inhibited the calcium influx caused by adrenaline and ATP. CONCLUSION: This study demonstrates that THGPA can modify cis-diol-mediated cell to-cell signaling. PMID- 26144263 TI - Current status of A1 adenosine receptor allosteric enhancers. AB - Adenosine is an ubiquitous nucleoside involved in various physiological and pathological functions by stimulating A1, A2A, A2B and A3 adenosine receptors (ARs). Allosteric enhancers to A1ARs may represent novel therapeutic agents because they increase the activity of these receptors by mediating a shift to their active form in the A1AR-G protein ternary complex. In this manner, they are able to amplify the action of endogenous adenosine, which is produced in high concentrations under conditions of metabolic stress. A1AR allosteric enhancers could be used as a justifiable alternative to the exogenous agonists that are characterized by receptor desensitization and downregulation. In this review, an analysis of some of the most interesting allosteric modulators of A1ARs has been reported. PMID- 26144264 TI - Progress toward rationally designed small-molecule peptide and peptidomimetic CXCR4 antagonists. AB - Over the last 5 years, X-ray structures of CXCR4 in complex with three different ligands (the small-molecule antagonist IT1t, the polypeptide antagonist CVX15 and the viral chemokine antagonist vMIP-II) have been released. In addition to the inherent scientific value of these specific X-ray structures, they provide a reliable structural foundation for studies of the molecular interactions between CXCR4 and its key peptide ligands (CXCL12 and HIV-1 gp120), and serve as valuable templates for further development of small-molecule CXCR4 antagonists with therapeutic potential. We here review recent computational studies of the molecular interactions between CXCR4 and its peptide ligands - based on the X-ray structures of CXCR4 - and the current status of small-molecule peptide and peptidomimetic CXCR4 antagonists. PMID- 26144265 TI - The impact of binding thermodynamics on medicinal chemistry optimizations. AB - Ligand binding thermodynamics has been attracted considerable interest in the past decade owing to the recognized relation between binding thermodynamic profile and the physicochemical and druglike properties of compounds. In this review, the relation between optimization strategies and ligand properties is presented based on the structural and thermodynamic analysis of ligand-protein complex formation. The control of the binding thermodynamic profile is beneficial for the balanced affinity and physicochemical properties of drug candidates, and early phase optimization gives more opportunity to this control. PMID- 26144266 TI - N-heterocyclic carbene metal complexes as bio-organometallic antimicrobial and anticancer drugs. AB - Late transition metal complexes that bear N-heterocyclic carbene (NHC) ligands have seen a speedy growth in their use as both, metal-based drug candidates and potentially active homogeneous catalysts in a plethora of C-C and C-N bond forming reactions. This review article focuses on the recent developments and advances in preparation and characterization of NHC-metal complexes (metal: silver, gold, copper, palladium, nickel and ruthenium) and their biomedical applications. Their design, syntheses and characterization have been reviewed and correlated to their antimicrobial and anticancer efficacies. All these initial discoveries help validate the great potential of NHC-metal derivatives as a class of effective antimicrobial and anticancer agents. PMID- 26144267 TI - Transcriptional analysis reveals distinct subtypes in amyotrophic lateral sclerosis: implications for personalized therapy. AB - Amyotrophic lateral sclerosis (ALS) is an incurable disease, caused by the loss of the upper and lower motor neurons. The lack of therapeutic progress is mainly due to the insufficient understanding of complexity and heterogeneity underlying the pathogenic mechanisms of ALS. Recently, we analyzed whole-genome expression profiles of motor cortex of sporadic ALS patients, classifying them into two subgroups characterized by differentially expressed genes and pathways. Some of the deregulated genes encode proteins, which are primary targets of drugs currently in preclinical or clinical studies for several clinical conditions, including neurodegenerative diseases. In this review, we discuss in-depth the potential role of these candidate targets in ALS pathogenesis, highlighting their possible relevance for personalized ALS treatments. PMID- 26144268 TI - Toxoplasma gondii coinfection with diseases and parasites in wild rabbits in Scotland. AB - In wild rabbits (Oryctolagus cuniculus) on an estate in Perthshire, central Scotland, the seroprevalence of Toxoplasma gondii was 18/548 (3.3%). The wild rabbit could be a T. gondii reservoir and it has potential value as a sentinel of T. gondii in environmental substrates. Toxoplasma gondii was associated with female sex (P < 0.001) and with relatively heavy infections by Eimeria stiedae (P = 0.036). It was not associated with the intensity of coccidial oocysts, the severity of myxomatosis caused by the virus Myxomatosis cuniculi, the intensity of roundworm eggs, the year or season, rabbit age or distance from farm buildings. Coinfections could have been affected by gestational down regulation of type 1 T helper cells. A sudden influx or release of T. gondii oocysts might have occurred. This is the first report of T. gondii in any wild herbivore in Scotland and also the first report of lapine T. gondii as a coinfection with E. stiedae, M. cuniculi and helminths. PMID- 26144269 TI - [Intestinal volvulus. Case report and a literature review]. AB - BACKGROUND: Small bowel volvulus is a rare cause of intestinal obstruction in adult patients. This disease is more common in children and its aetiology and management is different to that in adults. CLINICAL CASE: A 30 year-old male with sarcoidosis presents with acute abdomen and clinical data of intestinal obstruction. Small bowel volvulus is diagnosed by a contrast abdominal tomography and an exploratory laparotomy is performed with devolvulation and no intestinal resection. In the days following surgery, he developed a recurrent small bowel volvulus, which was again managed with surgery, but without intestinal resection. Medical treatment for sarcoidosis was started, and with his clinical progress being satisfactory,he was discharged to home. CONCLUSIONS: Making an early and correct diagnosis of small bowel volvulus prevents large intestinal resections. Many surgical procedures have been described with a high rate of complications. Therefore, conservative surgical management (no intestinal resection) is recommended as the best treatment with the lowest morbidity and mortality rate. PMID- 26144270 TI - [Hepatic angiosarcoma and liver transplantation: case report and literature review]. AB - BACKGROUND: Hepatic angiosarcoma is a rare vascular malignancy that accounts for 2% of all hepatic primary tumours. The diagnosis is difficult, especially if the patient does not have history of exposure to carcinogens, which are considered as risk factors. The diagnosis is made by histopathology, but in a considerable percentage it can only be accomplished by autopsy. The performing of fine needle aspiration biopsy can lead to bleeding, with limitations in its use. CLINICAL CASE: A 41 year-old male, with no history of exposure to carcinogens, who developed abdominal pain secondary to a haemoperitoneum due to tumour rupture, was diagnosed by imaging methods with a giant cavernous hepatic haemangioma. He was initially treated with embolisation, and later with a liver transplant. After six months he developed haemoptysis secondary to lung metastasis. The autopsy reported metastatic hepatic angiosarcoma. DISCUSSION: This condition has been related to carcinogen exposure, with malignant transformation from a benign vascular neoplasia being proposed as a hypothesis. The differential diagnosis can be achieved with imaging studies such as CT scan, and the definitive diagnosis is made by histopathology with immunohistochemistry tests, with 35%-100% being made in the autopsy. CONCLUSION: Hepatic angiosarcoma is a malignant vascular neoplasia, the potential curative option is surgery with tumour free margins. Liver transplantation remains controversial because of its poor prognosis in the short term. PMID- 26144271 TI - Intrahepatic triglyceride content is independently associated with chronic kidney disease in obese adults: A cross-sectional study. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are associated with some common critical cardio-metabolic risk factors. The aim of this study was to explore the association between intrahepatic triglyceride (IHTG) content and CKD in obese subjects. METHODS: A total of 1068 obese participants received anthropometric, biochemical measurements and hepatic ultrasonography. Of those, 485 participants received magnetic resonance spectroscopy ((1)H-MRS) for the determination of IHTG content. CKD was defined as a urinary albumin:creatinine ratio (UACR)>=30 mg/g and/or estimated glomerular filtration rate (eGFR)<60 mL/min per 1.73 m(2). RESULTS: The prevalence of CKD was significantly higher in NAFLD subjects compared to subjects without NAFLD, while the prevalence of CKD was gradually increased as the IHTG content increased by quartiles (P for trend<0.001). After adjustment for multivariate metabolic factors, the risk of abnormal albuminuria and CKD was increased by 68% [OR (95% CI): 1.68 (1.21-2.33), P<0.01] and 54% [OR (95% CI): 1.54 (1.14-2.07), P<0.01] respectively per one standard deviation (SD) increase in IHTG content. The association between IHTG content and CKD was not changed by conventional risk factors, including age, BMI and hypertension (all P<0.05). CONCLUSION: IHTG content is independently associated with CKD in obese adults. PMID- 26144272 TI - Career pathways of board-certified surgeons in Japan. AB - PURPOSE: To investigate the career pathways of board-certified surgeons' and the factors associated with them maintaining their certification in Japan. METHODS: We analyzed data from the surveys of physicians, dentists and pharmacists. A multivariate logistic regression model was used to investigate whether factors such as gender, year of registration, place of work, and subspecialty board certification were associated with maintaining board certification. RESULTS: Most Japanese surgeons attain board certification within 5-10 years of initial medical registration. After adjusting for possible confounding factors, the odds of maintaining board certification were significantly lower for women, those who were beyond 20 years post-registration, those who worked in hospitals other than academic hospitals or clinics, and those who had board certification in surgery only. Of the total board-certified surgeons analyzed, 93.2 % continued to work in hospitals and 2.8 % moved to clinics within 2 years. Of those who moved from hospitals to clinics, half continued to practice surgery, while nearly 40 % changed their specialty to internal medicine. CONCLUSION: It is necessary to establish a special training system for mature surgeons who move from surgery to general practice later in their careers. As the number of female surgeon increases, a support system is also required to secure the future supply of surgeons. PMID- 26144273 TI - Green Synthesis of Oxovanadium(IV)/chitosan Nanocomposites and Its Ameliorative Effect on Hyperglycemia, Insulin Resistance, and Oxidative Stress. AB - In this paper, the preparation, characterization, and ameliorative effect on high fat high-sucrose diet-induced hyperglycemia, insulin resistance, oxidative stress in mice of novel oxovanadium(IV)/chitosan (OV/CS) nanocomposites were investigated. The nanobiocomposite was produced by chemical reduction by chitosan and L-ascorbic acid using microwave heating, under environment-friendly conditions, using aqueous solutions, and notably, by using both mediators as reducing and stabilizing agents. In addition, OV/CS nanocomposites were characterized by transmission electron microscopy, energy dispersive spectroscopy, particle size, and zeta potential measurements. In vivo experiments were designed to examine whether the OV/CS nanocomposites would provide additional benefits on oxidative stress, hyperglycemia, and insulin resistance in mice with type 2 diabetes. The results rendered insulin resistant by treating with OV/CS nanocomposites alleviate insulin resistance and improve oxidative stress. Such nanocomposite seem to be a valuable therapy to achieve and/or maintain glycemic control and therapeutic agents in the treatment arsenal for insulin resistance and type 2 diabetes. PMID- 26144274 TI - [Cannabis use: what to do in general practice?]. AB - Cannabis use is now more frequent than alcohol drinking or tobacco smoking among young people (15-34years), whereas it may induce numerous medical aftermaths. Identifying and assessing cannabis use in general practice have become a current public health issue. The two steps of screening consist in spotting risky use of cannabis, and then in checking criteria for cannabis use disorder (CUD). Risky use requires a "brief intervention" by the general practitioner (GP). In case of CUD, the new DSM-5 criteria allow measuring the severity of the subsequent disorder, and listing the medical and social consequences. Using these criteria can help the GP to decide when the patient should be referred to an addiction specialized unit. The GP has also to spot the different physical and psychiatric complications of cannabis use, in order to coordinate care between the different specialists. PMID- 26144275 TI - [Resistant hypertension and carotid baroreceptors stimulation]. AB - Resistant hypertension remains a frequent and difficult situation; its management has been recently clarified by guidelines from the French Society of Hypertension. Baroreceptor stimulation (BAROSTIM) is an emerging technique aimed at decreasing blood pressure in resistant hypertension. BAROSTIM interferes with baroreflex loop by stimulating baroreceptors and afferences of the baroreflex. There is only one randomized control trial with this technique which showed a modest but apparently durable blood pressure reduction. More evidences are required to refine the place of BAROSTIM, particularly with new devices. Together with renal denervation, BAROSTIM belongs to a new family of interventional techniques which should be considered as potential add-on therapies while optimal medical therapy remains the cornerstone of hypertension management. PMID- 26144276 TI - The Log book for the secondary prevention of coronary artery disease: A pilot study. AB - INTRODUCTION: In secondary prevention (SP) of coronary artery disease (CAD), in particular after an acute myocardial infarction (MI), a better knowledge and self management by the patient may have various supports. The Log book (LB) for CAD patients in Cote d'Or, was created in 2010 by a multidisciplinary team of healthcare professionals of Cote d'Or, from a regional care network. This pilot study evaluated LB as novel support for SP after acute MI. METHODS: A prospective study on 183 patients hospitalised for an acute MI in the region of Cote d'Or from 1st May to 30th October 2010. Patients were randomized in 91 patients who received an LB at the time of their hospitalisation (LB+ group), and 92 patients who were not given an LB (LB- group). The follow up (FU) was performed at 4 months and 1 year. RESULTS: Baseline characteristics were similar in the 2 groups, except for smoking, which was more frequent in the LB-group than in the LB+ group. At FU, LB was usually well accepted by both patients and their general practitioners (GP). At 4 months FU, the patients LB+ were more prone to see their general practitioners than patients LB- (100% vs 85% in the LB- group, P=0.007). Moreover, in LB+ group, there was a trend towards a more frequent physical activity, including exercise bike (P=0.009) and an increase in HDL-cholesterol (HDL-c) (P=0.165). At 1 year FU, body mass index from LB+ was more reduced than in patients LB- (P=0.029). Finally, there was a trend towards lower morbi mortality (hospitalisation for cardiovascular cause or death) in the LB+ group than in the LB- group (11 vs 22%, P=0.083). CONCLUSION: This pilot study showed the feasibility of LB as a support for SP and its interest in post MI management in a local care network setting. In addition, our study provides encouraging data on the potential benefits of this pioneer tool for SP. PMID- 26144277 TI - [Condylama lata]. PMID- 26144278 TI - PEComa: morphology and genetics of a complex tumor family. AB - Perivascular epithelioid cell tumors, or PEComas, are mesenchymal neoplasms composed of histologically and immunohistochemically distinctive epithelioid or spindle cells, which are immunoreactive for both smooth muscle and melanocytic markers. The cells in PEComas are typically arranged around blood vessels and appear to form the vessel wall, often infiltrating the smooth muscle of small- to medium-sized vessels. Periluminal cells are usually epithelioid and the more peripheral cells are spindle shaped. The cells have small, round to oval nuclei, sometimes with focal nuclear atypia, and clear to eosinophilic cytoplasm, and no counterpart normal cell has been identified. The PEComa "family" now includes angiomyolipoma, pulmonary clear cell "sugar" tumor and lymphangioleiomyomatosis, primary extrapulmonary sugar tumor, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, abdominopelvic sarcoma of perivascular epithelioid cells, and other tumors with similar features at various sites that are simply termed PEComa. Some PEComas occur in patients with tuberous sclerosis complex and share the genetic abnormalities. There is a behavioral spectrum from benign to frankly malignant, and histologic criteria have been proposed for assessing malignant potential. The differential diagnosis can include carcinomas, smooth muscle tumors, other clear cell neoplasms, and adipocytic tumors. PEComas constitute a genetically diverse group that includes neoplasms harboring TFE3 gene rearrangements and those with TSC2 mutations, indicating alternative tumorigenic pathways. Recent advances in therapy of malignant PEComas relate to increased knowledge of specific genetic changes and their effects on metabolic pathways that are susceptible to specific interventions. We review PEComas, emphasizing the diagnostic spectrum and recent immunohistochemical and genetic findings. PMID- 26144279 TI - Sonoelastographic strain index in the early diagnosis of plantar fasciitis. PMID- 26144280 TI - Altered glutathione system is associated with the presence of distal symmetric peripheral polyneuropathy in type 2 diabetic subjects. AB - Distal symmetric peripheral polyneuropathy (DSPN) is a highly prevalent complication of diabetes. However, underlying pathophysiological mechanisms are multiple and not well understood. The aim of our study was to analyze the oxidative stress levels in circulating mononuclear cells by measuring the glutathione system, malondialdehyde and oxidized-LDL, in 60 type 2 diabetic patients from a well-characterized cohort of 196 type 2 diabetic patients. Using a nested case-control design, we studied 30 type 2 diabetic patients with distal symmetric polyneuropathy and 30 diabetic controls without this complication, according to the Neuropathy Disability Score. We have found that diabetic patients with distal symmetric polyneuropathy showed significantly lower values of reduced glutathione (GSH) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio. These data indicate an increased consumption of glutathione in mononuclear cells from patients with distal symmetric polyneuropathy. No significant differences were found in malondialdehyde or in oxidized-LDL levels comparing both groups. These data show an altered glutathione response in circulating monocytes from diabetic patients with distal symmetric polyneuropathy. PMID- 26144281 TI - Association of adiponectin gene polymorphisms with an elevated risk of diabetic peripheral neuropathy in type 2 diabetes patients. AB - OBJECTIVE: In this study, we examined the association between two adiponectin (ADPN) gene polymorphisms, +45T/G and +276G/T, and susceptibility to diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 180 T2DM patients were enrolled in this study and assigned to two groups: DPN group (n=90) and non-DPN (NDPN) group (n=90). In addition, 90 healthy subjects were chosen as healthy normal control (NC). The plasma level of ADPN was quantified by ELISA method and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotype analysis of the two ADPN polymorphisms, +45T/G (rs2241766) and +276G/T (rs1501299), in all the study subjects. Statistical analysis of data was performed with SPSS version 20.0 software. RESULTS: Serum levels of ADPN were markedly reduced in the DPN group compared to NDPN and NC groups (all P<0.05). The frequencies of TT, TG and GG genotypes and the T and G alleles of T45G and G276T polymorphisms in DPN group were significantly different than the NDPN group (all P<0.05). Notably, T45G and G276T polymorphisms were associated with significantly reduced plasma levels of ADPN in DPN and NDPN groups, compared to the NC group (P<0.001). Significant difference in ADPN plasma levels were also observed between TT, TG and GG genotypes of T45G and G276T polymorphisms. Our results indicate that the T allele in +45T/G and +276G/T polymorphisms is correlated with an elevated risk of DPN in T2DM patients. Haplotype analysis showed that GG and GT haplotypes showed a negative relationship with DPN, while TG haplotype positively correlated with risk of DPN in T2DM patients (all P<0.05). CONCLUSION: Our results show that T45G and G276T polymorphisms of ADPN are associated with a significantly elevated risk of DPN in T2DM patients, likely by down-regulating ADPN serum level. PMID- 26144282 TI - Cellular stress induces cap-independent alpha-enolase/MBP-1 translation. AB - Myc promoter-binding protein-1 (MBP-1) is a shorter protein variant of the glycolytic enzyme alpha-enolase. Although several lines of evidence indicate that MBP-1 acts as a tumor suppressor, the cellular mechanisms and signaling pathways underlying MBP-1 expression still remain largely elusive. To dissect these pathways, we used the SkBr3 breast cancer cell line and non-tumorigenic HEK293T cells ectopically overexpressing alpha-enolase/MBP-1. Here, we demonstrate that induced cell stresses promote MBP-1 expression through the AKT/PERK/eIF2alpha signaling axis. Our results contribute to shedding light on the molecular mechanisms underlying MBP-1 expression in non-tumorigenic and cancer cells. PMID- 26144283 TI - Discovery of a Novel HDAC2 Inhibitor by a Scaffold-Merging Hybrid Query. AB - Histone deacetylases (HDACs) are part of a vast family of enzymes with crucial roles in numerous biological processes, largely through their repressive influence on transcription, with serious implications in a variety of human diseases. Among different isoforms, human HDAC2 in particular draws attention as a promising target for the treatment of cancer and memory deficits associated with neurodegenerative diseases. Now the challenge is to obtain a compound that is structurally novel and truly selective to HDAC2 because most current HDAC2 inhibitors do not show isoforms selectivity and suffer from metabolic instability. In order to identify novel, and isoform-selective inhibitors for human HDAC2, we designed a shape-based hybrid query from multiple scaffolds of known chemical classes and validated it to be a more effective approach to discover diverse scaffolds than single-molecule query. The hybrid query-based screening rendered a hit compound with the N-benzylaniline scaffold which showed moderate inhibitory activity against HDAC2, and its chemical structure is diverse compared to known HDAC2 inhibitors. Notably, this compound shows the selectivity against the HDAC6, a Class II enzyme, thus has the potential to further develop into the class- and isoform-selective inhibitors. Our present study supplies an useful approach to identifying novel HDAC2 inhibitors, and can be extended to the inquires of other important biomedical targets as well. PMID- 26144284 TI - Comparing 30-day outcomes between thoracoscopic and open approaches for resection of pediatric congenital lung malformations: Evidence from NSQIP. AB - BACKGROUND/PURPOSE: Thoracoscopic surgery has been increasingly utilized in treating pediatric congenital lung malformations (CLM). Comparative studies evaluating 30-day outcomes between thoracoscopic and open resection of CLM are lacking. METHODS: There were 258 patients identified in pediatric NSQIP with a CLM and pulmonary resection in 2012-2013. Comparisons of patient characteristics and outcomes between surgical approaches were made using standard univariate statistics. In addition, a propensity score match was performed to evaluate outcomes in similar patient cohorts. RESULTS: One-hundred twelve patients (43.4%) received thoracoscopic resections and 146 patients (56.6%) received open resections. Patients undergoing open resections were more likely to be less than 5 months of age and have a comorbidity/preoperative condition (47.3% vs. 25.0%, p<0.001). The extent of resection was a lobectomy in 84.8% of thoracoscopic and 92.5% of open resection patients. Median operative time was similar between both groups (thoracoscopic 172 vs. open 153.5 minutes). On univariate analysis, thoracoscopic resection was associated with decreased postoperative complications (9.8% vs. 25.3%, p=0.001) and LOS (3 vs. 4 days, p<0.001). However, after adjusting for similar patient and operative characteristics, no significant differences were encountered between techniques. CONCLUSIONS: Thoracoscopic and open resection provide comparable 30-day outcomes and safety in the management of congenital lung malformations. PMID- 26144285 TI - Bud extracts from Tilia tomentosa Moench inhibit hippocampal neuronal firing through GABAA and benzodiazepine receptors activation. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tilia tomentosa Moench bud extracts (TTBEs) is used in traditional medicine for centuries as sedative compound. Different plants belonging to the Tilia genus have shown their efficacy in the treatment of anxiety but still little is known about the mechanism of action of their bud extracts. AIM OF THE STUDY: To evaluate the action of TTBEs as anxiolytic and sedative compound on in vitro hippocampal neurons. MATERIAL AND METHODS: The anxiolytic effect of TTBEs was assayed by testing the effects of these compounds on GABAA receptor-activated chloride current of hippocampal neurons by means of the patch-clamp technique and microelectrode-arrays (MEAs). RESULTS: TTBEs acutely administered on mouse hippocampal neurons, activated a chloride current comparable to that measured in the presence of GABA (100 uM). Bicuculline (100 uM) and picrotoxin (100 uM) blocked about 90% of this current, while the remaining 10% was blocked by adding the benzodiazepine (BDZ) antagonist flumazenil (30 uM). Flumazenil alone blocked nearly 60% of the TTBEs activated current, suggesting that TTBEs binds to both GABAA and BDZ receptor sites. Application of high-doses of TTBEs on spontaneous active hippocampal neurons grown for 3 weeks on MEAs blocked the synchronous activity of these neurons. The effects were mimicked by GABA and prevented by picrotoxin (100uM) and flumazenil (30 uM). At minimal doses, TTBEs reduced the frequency of synchronized bursts and increased the cross-correlation index of synchronized neuronal firing. CONCLUSIONS: Our data suggest that TTBEs mimics GABA and BDZ agonists by targeting hippocampal GABAergic synapses and inhibiting network excitability by increasing the strength of inhibitory synaptic outputs. Our results contribute toward the validation of TTBEs as effective sedative and anxiolytic compound. PMID- 26144286 TI - A case of BK virus nephropathy in a stem cell transplant recipient: a rare or under-recognized cause for Acute Kidney injury. PMID- 26144287 TI - Testicular orphan receptor 4 (TR4) is a marker for metastasis and poor prognosis in non-small cell lung cancer that drives the EMT phenotype. AB - OBJECTIVES: Aberrant expression of testicular orphan receptor 4 (TR4) has been shown to regulate biological processes near solid tumors. However, the role of TR4 in non-small cell lung cancer (NSCLC) patient prognosis and the development of NSCLC cancer cells are unclear. METHODS: Immunohistochemical analysis was used to evaluate the correlation between TR4 expression and clinicopathological characteristics in 291 cases of NSCLC specimens. A knockdown and overexpression of TR4 was performed to assess the role of TR4. Transwell and colony formation assays were completed to investigate the metastatic and proliferative abilities. Quantitative real-time PCR, Western blotting and immunofluorescence staining were carried out to analyze the epithelial-to-mesenchymal transition (EMT) phenotype. RESULTS: Immunohistochemical evaluation of clinical samples revealed that most of the lung cancer tissues were strongly positive for TR4, whereas the tissues that stained weakly positive or negative for TR4 expression were shown in the paired normal tissues. Moreover, higher levels of TR4 expression were significantly associated with higher lymph node metastases, TNM stages, tumor thrombus in vena and poor prognosis. We observed that downregulation and up-regulation of TR4 with stable cell transfection significantly influence the proliferation, invasive and metastatic abilities of NSCLC lines. In addition, aberrant TR4 expression could modulate the expression levels of several EMT related markers. CONCLUSIONS: Collectively, our results show TR4 expression in NSCLC samples is significantly associated with poor clinicopathological features, and TR4 plays an important role in the metastatic capacity of NSCLC cells by EMT regulation. PMID- 26144288 TI - [Evaluation of adherence to French guidelines concerning the information of the women having a scarred uterus on their mode of delivery]. AB - OBJECTIVE: To evaluate adherence of obstetricians from our maternity to French practice guidelines concerning information to give to pregnant patients with a history of scarred uterus. MATERIALS AND METHODS: Observational retrospective study performed on medical files from June to August 2014 and concerning women with a scarred uterus that gave live-birth after 37weeks of gestation. Information of patients had to concern the risks of a history of caesarean, the benefits and risks of the various delivery modes. RESULTS: On 758 deliveries, 77 cases were studied: 48 patients were followed up from the beginning of pregnancy, 23 from the 2nd trimester and 6 were not followed. Among patients followed from the beginning, no data was written on medical file concerning information that should to be given in immediate post-partum, in preconception counseling, and at the beginning of pregnancy about the risks of scarred uterus and the mode of delivery. In the 8th month, information about benefits and risks of the planned delivery mode was noticed in 45% of files. CONCLUSION: The information that need in theory to be given to the patients with scarred uterus appeared little or insufficiently noticed on medical files; which can be due either to an inaccurate information, or to a lack of transcription of the information nevertheless given. A check-list in obstetrical file would help to systematize the information to provide in scarred uterus patients. PMID- 26144289 TI - [Cervical cerclage]. AB - Cervical cerclage aims to strengthen not only the mechanical properties of the cervix, but also its immunological and anti-infectious functions. The demonstration of a strong interrelation between cervical insufficiency as well as decreased cervical length at endo-vaginal ultrasonography and infection has changed the indications cerclage. Actually we can distinguish three indications for cerclage: prophylactic, for obstetrical history; therapeutic, for shortened cervical length at ultrasonography in patients at risk and; emergency cerclage in case of threatening cervix at physical examination. The McDonald's technique is the most recommended. In case of failure, it is proposed to realize cerclage at a higher level on the cervix either by vaginal or abdominal route. PMID- 26144290 TI - Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia. AB - Many organs throughout the body maintain epithelial homeostasis by employing a mucosal barrier which acts as a lubricant and helps to preserve a near-sterile epithelium. Goblet cells are largely responsible for secreting components of this mucosal barrier and represent a major cellular component of the innate defense system. In this review we summarize what is known about the signaling pathways that control goblet cell differentiation in the intestine, the lung, and the ocular surface, and we discuss a novel functional role for goblet cells in mucosal epithelial immunology. We highlight the cell type-specificity of the circuitry regulating goblet cell differentiation and shed light on how changes to these pathways lead to altered goblet cell function, a prominent feature of mucosa-associated diseases. PMID- 26144291 TI - Interplay between inflammatory and estrogen signaling in breast cancer. AB - Inflammation is known to have a paradoxical effect in cancers, in some cases promoting pathogenesis while in others inhibiting pathogenesis, depending on the cellular context. In an effort to answer a number of fundamental questions about two of the major signaling cascades that affect breast tumorigenesis and impact clinical outcome, we examined the genome-wide consequences of treating ERalpha positive breast cancer cells with both estrogen and TNFalpha. Below, we highlight our observations, their biological significance, and how they provide a framework for understanding the molecular basis for integration of proinflammatory and estrogen signaling in breast cancer. PMID- 26144292 TI - The role of interleukin-32 against tuberculosis. AB - IL-32 is increasingly recognized to be an important host-protective molecule against tuberculosis. In this commentary, we highlight some of the potential mechanisms by which the immunomodulatory effect of IL-32 occurs against mycobacterial infections but also areas where mechanistic clarifications are needed. PMID- 26144293 TI - Endothelin 1 and transforming growth factor-beta1 correlate with liver function and portal pressure in cirrhotic patients. AB - OBJECTIVE: The invasive measurement of hepatic venous pressure gradient is the recommended method for the assessment of portal hypertension. We assessed if the mediators that regulate portal hypertension may be used as noninvasive markers of portal hypertension and liver insufficiency. MATERIALS AND METHODS: We explored in prospective, observational study the concentration of endothelin-1, nitric oxide, and transforming growth factor-beta1/2 in peripheral and hepatic venous blood; their relationship with the values of portal hypertension and liver insufficiency; and their level changes 4-6 months after non-selective beta blocker therapy in cirrhotic patients with non-bleeding esophageal varices. RESULTS: (1) Cirrhotics have significantly increased peripheral endothelin 1 and decreased transforming growth factor-beta1 levels; (2) peripheral levels of all factors correlated significantly with their hepatic levels; (3) after therapy, peripheral endothelin-1 levels significantly increased, but transforming growth factor-beta2 levels decreased and were lower in patients with pressure gradient value normalization; (4) before and after therapy, peripheral and hepatic endothelin-1, transforming growth factor-beta1/2 levels correlated significantly with liver failure indicators (laboratory parameters, Child-Pough and MELD scores) and pressure gradient values. CONCLUSIONS: Peripheral endothelin-1 and transforming growth factor-beta1 levels, which strongly correlate with their hepatic levels, reflect the stage of portal hypertension and liver insufficiency in cirrhosis. PMID- 26144294 TI - Maternal serum omentin-1 profile is similar in humans and in the rat animal model. AB - Omentin-1 is an adipocytokine with anti-inflammatory activity that has been associated with different metabolic disorders. The aim of this study is to investigate the serum profiles of omentin-1 throughout human and rat pregnancy. Serum omentin-1 levels were determined by ELISA in a prospective cohort study of healthy pregnant women (n=40) during the three trimesters of pregnancy and in twenty healthy non-pregnant women during the follicular and luteal phase of the menstrual cycle. In addition, serum omentin-1 levels were measured in rats during different periods of pregnancy (gestational days 8, 12, 16, 19, and 21) and in an age-matched control (virgin) group of rats (n=12rats/group). Finally, immunohistochemistry was used to demonstrate the presence of omentin-1 protein in human and rat placenta. Omentin-1 immunoreactivity was detected in cytotrophoblasts, syncytiotrophoblasts, sparse Hofbauer cells, and endothelial cells of the stem villi of human placenta. Additionally, it was detected in the labyrinthine trophoblast and yolk sac layer of the rat placenta. Human and rat serum omentin-1 levels were significantly lower in the late gestational period when compared with the non-pregnant women and virgin rats (p<0.05). Serum omentin 1 changes were not significant throughout the gestation in both species (p>0.05). Human serum omentin-1 levels have an inverse relationship with triglyceride levels during pregnancy. Our findings have not determined the exact role of omentin-1 during pregnancy, concerning the metabolic control of triglycerides and other energy sources. Whether omentin-1 decrease implies a regulatory function is still not clear. Further studies are needed to address this issue and determine the role of omentin-1 in metabolic adaptations during normal human and rat pregnancy. PMID- 26144314 TI - A prospective study of community-associated Clostridium difficile infection in Kuwait: Epidemiology and ribotypes. AB - Clostridium difficile infection (CDI) is increasingly recognized as a significant community acquired pathogen that causes disease in the community. The aim of the study was to investigate prospectively the incidence of community-acquired-CDI (CA-CDI) in Kuwait. Of the 2584 patients with diarrhea, 16 (0.62%) were confirmed cases of CA-CDI. The other notable pathogens were Salmonella spp. (0.39%) and Campylobacter spp. (0.23%). The mean age was 39 years and the CDI was mild. Exposure to antibiotics in the previous 12 weeks, contact with infant aged <2 years and history of foreign travel was significantly associated with CA-CDI (P < 0.001; P < 0.0001; P < 0.002, respectively). Detected PCR ribotypes were 139 (n = 4) and 014, 056, 070, 097 and 179 (each n = 2). CA-CDI in Kuwait is more likely to occur in younger age and associated with ribotype 139. CA-CDI is not a common problem in Kuwait however extra vigilance must be maintained to detect it in the community even without traditional predisposing factors. PMID- 26144315 TI - PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. AB - We report the preclinical evaluation of PF-06463922, a potent and brain-penetrant ALK/ROS1 inhibitor. Compared with other clinically available ALK inhibitors, PF 06463922 displayed superior potency against all known clinically acquired ALK mutations, including the highly resistant G1202R mutant. Furthermore, PF-06463922 treatment led to regression of EML4-ALK-driven brain metastases, leading to prolonged mouse survival, in a superior manner. Finally, PF-06463922 demonstrated high selectivity and safety margins in a variety of preclinical studies. These results suggest that PF-06463922 will be highly effective for the treatment of patients with ALK-driven lung cancers, including those who relapsed on clinically available ALK inhibitors because of secondary ALK kinase domain mutations and/or brain metastases. PMID- 26144316 TI - The Utilization of Extracellular Proteins as Nutrients Is Suppressed by mTORC1. AB - Despite being surrounded by diverse nutrients, mammalian cells preferentially metabolize glucose and free amino acids. Recently, Ras-induced macropinocytosis of extracellular proteins was shown to reduce a transformed cell's dependence on extracellular glutamine. Here, we demonstrate that protein macropinocytosis can also serve as an essential amino acid source. Lysosomal degradation of extracellular proteins can sustain cell survival and induce activation of mTORC1 but fails to elicit significant cell accumulation. Unlike its growth-promoting activity under amino-acid-replete conditions, we discovered that mTORC1 activation suppresses proliferation when cells rely on extracellular proteins as an amino acid source. Inhibiting mTORC1 results in increased catabolism of endocytosed proteins and enhances cell proliferation during nutrient-depleted conditions in vitro and within vascularly compromised tumors in vivo. Thus, by preventing nutritional consumption of extracellular proteins, mTORC1 couples growth to availability of free amino acids. These results may have important implications for the use of mTOR inhibitors as therapeutics. PMID- 26144318 TI - G1/S Inhibitors and the SWI/SNF Complex Control Cell-Cycle Exit during Muscle Differentiation. AB - The transition from proliferating precursor cells to post-mitotic differentiated cells is crucial for development, tissue homeostasis, and tumor suppression. To study cell-cycle exit during differentiation in vivo, we developed a conditional knockout and lineage-tracing system for Caenorhabditis elegans. Combined lineage specific gene inactivation and genetic screening revealed extensive redundancies between previously identified cell-cycle inhibitors and the SWI/SNF chromatin remodeling complex. Muscle precursor cells missing either SWI/SNF or G1/S inhibitor function could still arrest cell division, while simultaneous inactivation of these regulators caused continued proliferation and a C. elegans tumor phenotype. Further genetic analyses support that SWI/SNF acts in concert with hlh-1 MyoD, antagonizes Polycomb-mediated transcriptional repression, and suppresses cye-1 Cyclin E transcription to arrest cell division of muscle precursors. Thus, SWI/SNF and G1/S inhibitors provide alternative mechanisms to arrest cell-cycle progression during terminal differentiation, which offers insight into the frequent mutation of SWI/SNF genes in human cancers. PMID- 26144317 TI - Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy. AB - The large (L) proteins of non-segmented, negative-strand RNA viruses, a group that includes Ebola and rabies viruses, catalyze RNA-dependent RNA polymerization with viral ribonucleoprotein as template, a non-canonical sequence of capping and methylation reactions, and polyadenylation of viral messages. We have determined by electron cryomicroscopy the structure of the vesicular stomatitis virus (VSV) L protein. The density map, at a resolution of 3.8 A, has led to an atomic model for nearly all of the 2109-residue polypeptide chain, which comprises three enzymatic domains (RNA-dependent RNA polymerase [RdRp], polyribonucleotidyl transferase [PRNTase], and methyltransferase) and two structural domains. The RdRp resembles the corresponding enzymatic regions of dsRNA virus polymerases and influenza virus polymerase. A loop from the PRNTase (capping) domain projects into the catalytic site of the RdRp, where it appears to have the role of a priming loop and to couple product elongation to large-scale conformational changes in L. PMID- 26144319 TI - Bladder-Rectum Spacer Balloon versus Vaginal Gauze Packing in High Dose Rate Brachytherapy in Cervical Cancer: A Randomised Study. Part II. AB - AIMS: To compare the inter-fraction dose variation for bladder and rectum using a bladder-rectum spacer balloon (BRSB) versus vaginal gauze packing (VGP) in patients treated with high dose rate intracavitary brachytherapy for carcinoma cervix. MATERIALS AND METHODS: After the completion of external radiotherapy, 80 patients were randomised to receive intracavitary brachytherapy using either the BRSB or VGP. The procedure was carried out under general anaesthesia using tandem ovoid applicators. Computed tomography-based planning was carried out and the dose was prescribed to point A. Doses to 0.1, 1 and 2 cm(3) volumes were reported for bladder and rectum for each fraction. The absolute inter-fraction dose variation for each subvolume was compared using the independent sample t-test. RESULT: The mean bladder and rectal volumes, as well as the inter-fraction volume variation, were comparable for the BRSB and VGP. The BRSB resulted in a significant reduction in absolute dose as well as the inter-fraction variation for dose to 2 cm(3) rectum volumes (BRSB 0.80 Gy, standard deviation 0.71 Gy versus VGP 1.16 Gy, standard deviation 0.83 Gy; P = 0.04). Cumulative bladder D2cm(3) doses of more than 90 Gy3 were observed in six patients in the BRSB arm versus four patients in the VGP arm (P = 0.73). In both the arms, the rectal D2cm(3) doses did not exceed 75 Gy3. CONCLUSIONS: Use of a BRSB resulted in a significant reduction in inter-fraction variation in D2cm(3) rectal dose. However, no significant difference in the inter-fraction dose variation for the other subvolumes of bladder and rectum could be shown between the BRSB and VGP. The use of a BRSB may enable rectal dose reduction and inter-fraction variation where anaesthesia is not routinely used or where there is limited physician expertise. The modification suggested in the BRSB may facilitate its additional usage. PMID- 26144320 TI - Re: Stereotactic Body Radiotherapy for Oligometastatic Disease. PMID- 26144333 TI - Intralesional Injection of Interferon-alpha2b Improves Penile Curvature in Men with Peyronie's Disease Independent of Plaque Location. AB - PURPOSE: Collagenase clostridium histolyticum is the only FDA (Food and Drug Administration) approved treatment for Peyronie's disease. However, to our knowledge collagenase clostridium histolyticum has not been studied in men with ventral plaques. Given this limitation and the paucity of literature on ventral plaque outcomes, we compared the results of Peyronie's disease treatment in men with different plaque locations treated with intralesional interferon-alpha2b. MATERIALS AND METHODS: We retrospectively analyzed the records of men treated with intralesional interferon-alpha2b for Peyronie's disease at 1 institution from 2001 to 2014. The men received 2 million U interferon-alpha2b injected every 2 weeks for 6 to 24 treatments. All men underwent penile duplex Doppler ultrasound before and after interferon-alpha2b treatment. Patient characteristics, penile duplex Doppler ultrasound and objective measurements were reviewed. Patients were stratified into ventral and dorsal/lateral plaque cohorts with a positive response defined as a 20% or greater reduction in curvature. RESULTS: A total of 131 patients with a mean+/-SD age of 53.8+/-9.5 years underwent a median of 12 intralesional interferon-alpha2b injections (range 6 to 24). Mean pretreatment dorsal curvature was 42.5+/-18.6 degrees in group 1 of 111 men and mean ventral curvature was 44.5+/-21.5 degrees in group 2 of 21 men (p=0.66). Overall 91% of patients responded to therapy. No significant difference was noted between the 2 groups in response rate (54% vs 52%, p=0.92) or absolute change in curvature (mean 8.7+/-12.6 vs 9.3+/-17.7 degrees, p=0.84). CONCLUSIONS: Treatment with intralesional interferon-alpha2b provided a greater than 20% reduction in curvature in the majority of men with Peyronie's disease. This improvement was independent of plaque location. PMID- 26144334 TI - Risk Factors for Postoperative Complications of Percutaneous Nephrolithotomy at a Tertiary Referral Center. AB - PURPOSE: We sought to describe and evaluate the complications related to percutaneous nephrolithotomy and identify risk factors of morbidity according to the modified Clavien scoring system. We also sought to specify which perioperative factors are associated with minor and major complications. MATERIALS AND METHODS: We retrospectively analyzed data on patients who underwent percutaneous nephrolithotomy from 1990 to 2013. Descriptive statistics were used to analyze patient characteristics, medical comorbidities and perioperative features. Complications were categorized according to the Clavien score for percutaneous nephrolithotomy. The Mann-Whitney and Fisher exact tests were used as appropriate. Logistic regression analysis was performed to look for prognostic factors associated with major complications. RESULTS: A total of 2,318 surgeries were evaluated. Mean age of the population was 53.7 years. The stone-free rate at hospital discharge was 81.6%. The overall complication rate was 18.3%. Two deaths occurred. Patients with any postoperative complications were older, had more comorbidities, were more likely to have staghorn calculi and had longer operative time and hospital stay on univariate analysis (p<0.05). Age 55 years or older and upper pole access were independent predictors of major complications on multivariate analysis. Other factors such as a history of urinary tract infections, body mass index, stone composition, previous percutaneous nephrolithotomy and multiple tracts were not associated with a major complication. CONCLUSIONS: At our center percutaneous nephrolithotomy is an excellent option for complex kidney stone management with a low overall complication rate. Older patient age and upper pole access are significantly associated with an increased risk of a major complication. PMID- 26144335 TI - Perinatal Outcomes with Tamsulosin Therapy for Symptomatic Urolithiasis. AB - PURPOSE: Medical expulsive therapy represents an effective adjunctive treatment for nonpregnant patients with symptomatic urolithiasis. Tamsulosin is classified by the FDA (Food and Drug Administration) as a category B medication. However, to our knowledge no published data exist for human pregnancy. We explored the safety and efficacy of tamsulosin therapy for symptomatic urolithiasis occurring during pregnancy. MATERIALS AND METHODS: We retrospectively identified patients treated with tamsulosin for stone disease during pregnancy at the Mayo Clinic during 2000 to 2014. This medical expulsive therapy cohort was matched 2:1 to pregnant women with symptomatic urolithiasis during pregnancy who did not receive medical expulsive therapy. Groups were compared using linear mixed models for continuous variables and exact conditional logistic regression models for nominal variables to take into account correlation due to matching. RESULTS: A total of 27 patients receiving medical expulsive therapy comprised the study cohort. Median duration of antepartum tamsulosin exposure was 3 days (range 1 to 110), occurring during the first, second and third trimester in 3 (11%), 11 (40.7%) and 18 (67%) patients, respectively. Mean gestational age at delivery was 38.1 weeks (SD 2.4) and 6 (22%) infants were born preterm. All infant birthweights were considered appropriate for gestational age, and no cases of spontaneous abortion, intrauterine demise or neonatal congenital anomalies were encountered. Comparison between the medical expulsive therapy and control groups demonstrated no significant differences in maternal or infant outcomes for any of the examined variables. CONCLUSIONS: Tamsulosin medical expulsive therapy does not appear to be associated with adverse maternal or fetal outcomes and may be considered as adjunctive therapy for urolithiasis during pregnancy. PMID- 26144336 TI - FGFR3 Down-Regulation is Involved in bacillus Calmette-Guerin Induced Bladder Tumor Growth Inhibition. AB - PURPOSE: Bacillus Calmette-Guerin is the standard treatment for patients with nonmuscle invasive high histological grade bladder cancer. Previously we found that bacillus Calmette-Guerin induces murine bladder cancer MB49 cell death in vitro and in vivo, generating tissue remodeling, which involves the release of fibroblast growth factor (FGF)-2. MATERIALS AND METHODS: We studied the effect of bacillus Calmette-Guerin treatment on FGF-2 and FGF receptor (FGFR) expression in bladder cancer. RESULTS: In vitro FGF-2 increased MB49 cell proliferation but did not reverse bacillus Calmette-Guerin induced cell death. Increased FGF-2 expression was detected after bacillus Calmette-Guerin treatment. Moreover MB49 cells expressed high FGFR3 levels, which decreased after treatment. Similar results were observed in human T24 bladder cancer cells. In vivo MB49 tumors expressed higher FGFR3 levels than normal urothelium. Tumor FGFR3 decreased after treatment and correlated with tumor growth inhibition in response to bacillus Calmette-Guerin. In a pilot bioassay using 11 human bladder tumors treated ex vivo with bacillus Calmette-Guerin we found a subgroup of 41% of patients in whom FGFR3 was decreased after treatment. CONCLUSIONS: Based on bladder cancer murine model results we infer that down-regulation of FGFR3 is a predictive marker of a good response to bacillus Calmette-Guerin therapy. The decrease in FGFR3 in response to bacillus Calmette-Guerin occurred not only in a murine model but also in a human bladder cancer cell line and in some patient samples. More patients and increased followup are needed to establish the predictive role of FGFR3 as a marker in human bladder cancer. PMID- 26144337 TI - Can Classic Bladder Exstrophy be Safely and Successfully Reconstructed at a Low Volume Center? AB - PURPOSE: Exstrophy reconstruction is challenging and requires expertise and experience. However, many patients are treated at low volume centers. We evaluated whether classic bladder exstrophy could be safely and successfully reconstructed at a low volume center. MATERIALS AND METHODS: A total of 31 patients with classic bladder exstrophy were primarily treated at our low volume center during a 17-year period. A total of 22 patients underwent primary closure within 5 days of birth and 9 underwent delayed closure with osteotomy. Of the patients 29 underwent planned modern staged repair and 2 underwent attempted complete primary repair. RESULTS: The bladder was successfully closed in all 31 children. All 22 newborns underwent primary bladder closure without osteotomy, including 4 with extremely small bladder plates. Bladder neck obstruction developed in 3 patients (10%), of whom 2 were treated successfully with transurethral dilation and 1 underwent open repair. Epispadias repair was successful in 12 of 15 patients undergoing the Cantwell-Ransley technique and in 2 of 4 undergoing complete primary repair. A total of 16 patients underwent bladder neck reconstruction, of whom 9 are awaiting appropriate age or capacity, 4 were lost to followup, 1 is continent after bladder closure alone and 2 underwent continent diversion (1 after failed bladder neck reconstruction). Of the 15 patients with at least 1 year of followup after bladder neck reconstruction 9 are continent day and night, 2 are continent only during the daytime and 4 are incontinent, for a 73% post-bladder neck reconstruction continence rate (11 of 15 patients). CONCLUSIONS: Successful exstrophy reconstruction is achievable at a low volume center, with results comparable to those of high volume centers. PMID- 26144338 TI - Incidence and Predictors for Ipsilateral Hydronephrosis Following Ureteroscopic Lithotripsy. AB - OBJECTIVE: To review our experience in using ureteroscopy (URS) with lithotripsy for renal or ureteral calculi to determine the incidence and predictors of postprocedural ipsilateral hydronephrosis. PATIENTS AND METHODS: Records of 324 URS cases for renal or ureteral calculi with imaging performed 4-12 weeks postprocedure were reviewed. Ipsilateral hydronephrosis was determined by computed tomography scan or renal ultrasound. Univariate and multivariate analyses determined the factors associated with hydronephrosis. RESULTS: 176 men and 148 women with a median age of 50 years were included. Median stone size was 6 mm and operative duration was 60 minutes; 30% of patients had multiple calculi; and 35% had undergone a prior ipsilateral URS. Overall, 49 of 324 patients (15%) had evidence of hydronephrosis, with 65% of these patients having symptoms and 40% requiring ancillary procedures. On multivariate analysis, increasing stone diameter (odds ratio [OR] 8.9, 95% confidence interval [CI] 1.9-23.8, P = .03), prior ipsilateral URS (OR 7.7, 95% CI 1.8-28.2, P = .006), longer operative duration (OR 6.5, 95% CI 1.8-16.3, P = .02), and renal colic symptoms (OR 48.3, 95% CI 14.7-71.4, P <.001) independently predicted hydronephrosis. Conversely, other factors including stone impaction at procedure, ureteral dilation, use of an access sheath, intraoperative perforation, or use of a stent did not associate with ipsilateral hydronephrosis. CONCLUSION: In this contemporary cohort study, 15% of patients undergoing URS had evidence of ipsilateral hydronephrosis. Larger stone size, longer OR duration, prior ipsilateral URS, and recurrent colic were associated with an increased likelihood for this observation. Patients and stone cases with such characteristics likely warrant imaging modalities beyond plain radiography. PMID- 26144339 TI - Factors Associated With the Lower Prevalence of Nephrolithiasis in Children Compared With Adults. AB - OBJECTIVE: To determine the reasons behind the lower prevalence of kidney stones in children by assessing urinary lithogenic parameters in healthy children, healthy adults, and 3 groups of stone-former patients. METHODS: The study subjects included 75 healthy adults, 105 healthy children, 62 patients with previous calcium oxalate monohydrate papillary stones, 120 patients with previous calcium oxalate monohydrate unattached stones, and 248 patients with previous calcium oxalate dihydrate stones. Twenty-four-hour urine samples were collected, and the urinary lithogenic parameters were measured. RESULTS: Calcium, magnesium, and phosphorous concentration differed significantly between healthy children and adults. Except citrate, all solute/creatinine ratios differed between healthy children and adults. However, these differences were much more important in the cases of calcium and magnesium. The calcium/creatinine ratio was 2-fold lower, whereas the magnesium/creatinine ratio was 2-fold higher, in healthy children than that in healthy adults (P <.001 each). The calcium/creatinine ratio was higher and the citrate/creatinine ratio lower in calcium oxalate dihydrate stone formers than that in healthy adults. CONCLUSION: Ratios of calcium and magnesium to creatinine, as well as morphoanatomic factors and lifestyle habits, may explain the lower prevalence of nephrolithiasis in children than those in adults. PMID- 26144340 TI - Incidentally Discovered Foley Catheter Placement Into a Transplanted Kidney. AB - Although unusual, placement of a Foley catheter into the renal pelvis or ureter has been reported. Proposed predisposing factors for errant placement include pre existing hydronephrosis or congenital ureteral orifice enlargement. We report a case where aberrant placement of a Foley catheter into the renal pelvis of a transplanted kidney was detected by ultrasound in a patient being evaluated for acute kidney injury. The Foley had been in place for 2 weeks. This is the only reported case we are aware of involving accidental catheterization of a transplant's renal pelvis. PMID- 26144341 TI - Multicenter Validation of Surgeon Assessment of Renal Preservation in Comparison to Measurement With 3D Image Analysis. AB - OBJECTIVE: To validate the findings of a prior single-surgeon series with a multi institutional comparison of three-dimensional imaging of volume preservation (3DVP) and surgeon assessment of volume preservation (SAVP) as predictors of renal function after partial nephrectomy (PN). Baseline renal function and preservation of functioning renal parenchyma are the strongest predictors of function after PN for presumed renal cancer. Prior studies have confirmed that measurement of volume preservation with 3DVP is accurate, but limited data exist to compare this time-consuming approach with SAVP. MATERIALS AND METHODS: 3DVP and SAVP were calculated for 157 patients operated on by 13 surgeons at 2 institutions having both pre- and postoperative cross-sectional imaging. Renal function was assessed by univariable and multivariable linear regression methods. RESULTS: Median ipsilateral parenchymal preservation was 87% by 3DVP (interquartile range: 76%-95%) and 85% by SAVP (interquartile range: 75%-90%). Both correlated strongly with each other (P <.0001) and no statistical differences in the correlation were observed for different individual surgeons. Each method was strongly correlated with postoperative glomerular filtration rate (P <.0001). Multivariable models using 3DVP and SAVP were statistically similar in predicting postoperative glomerular filtration rate (R(2) = 0.86 for both). However, SAVP was not interchangeable with 3DVP within a 5% margin of error (95% confidence interval: -0.11, 0.13) according to Bland-Altman analysis. CONCLUSION: SAVP has been validated in a multicenter cohort of PN patients demonstrating it to provide a reliable estimate of renal functional preservation that is reproducible in contemporary practice. We propose that SAVP reporting should be performed routinely to facilitate analysis of PN outcomes and 3DVP used for research purposes. PMID- 26144345 TI - Ligand efficient tetrahydro-pyrazolopyridines as inhibitors of ERK2 kinase. AB - A series of structure based drug design hypotheses and focused screening efforts drove improvements in the potency and lipophilic efficiency of tetrahydro pyrazolopyridine based ERK2 inhibitors. Elaboration of a fragment chemical lead established a new lipophilic aryl-Tyr interaction resulting in a substantial potency improvement. Subsequent cleavage of the lipophilic moiety led to reconfiguration of the ligand bound binding cleft. The reconfiguration established a polar contact between a newly liberated N-H and a vicinal Asp, resulting in further improvements in lipophilic efficiency and in vitro clearance. PMID- 26144346 TI - Exploration of the structure-activity relationship of 1,2,4-oxadiazole antibiotics. AB - We have recently disclosed the discovery of the class of 1,2,4-oxadiazole antibiotics, which emerged from in silico docking and scoring efforts. This class of antibacterials exhibits Gram-positive activity, particularly against Staphylococcus aureus. We define the structure-activity relationship (SAR) of this class of antibiotics with the synthesis and evaluation of a series of 59 derivatives with variations in the C ring or C and D rings. A total of 17 compounds showed activity against S. aureus. Four derivatives were evaluated against a panel of 16 Gram-positive strains, inclusive of several methicillin resistant S. aureus strains. These compounds are broadly active against Gram positive bacteria. PMID- 26144348 TI - Splenectomy exacerbates atrial inflammatory fibrosis and vulnerability to atrial fibrillation induced by pressure overload in rats: Possible role of spleen derived interleukin-10. AB - BACKGROUND: The spleen is important for cardiac remodeling induced by myocardial infarction. However, the role of the spleen in inflammatory atrial fibrosis induced by pressure overload is unknown. OBJECTIVE: The purpose of this study was to investigate whether splenectomy (SPX) attenuates or exacerbates pressure overload-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in rats. METHODS: Male Sprague-Dawley rats (6 weeks old) were divided into Sham+Sham, Sham+SPX, abdominal aortic constriction (AAC)+Sham, and AAC+SPX groups, and were evaluated for inflammation, fibrosis, and AF on days 2, 4, 14, and 28. RESULTS: On day 4, an AAC-induced rise in interleukin-10 (IL-10) level was observed in the spleen, serum, and left atrium (LA), with SPX showing inhibitory effects in the latter 2 instances. In addition, AAC-induced M2 macrophage recruitment into the LA was decreased by SPX, as determined by immunofluorescence labeling (P <.05). On day 28, AAC-induced heterogeneous interstitial fibrosis of the LA was enhanced by SPX (P <.05). Electrophysiologic recordings revealed that the duration of AF and prolongation of interatrial conduction time induced by AAC were increased by SPX (P < .01 and P <.05, respectively). Furthermore, in the AAC+SPX group, the number of macrophages infiltrating into the LA on day 2 was marginal, but increased on day 28 relative to the AAC+Sham group. IL-10 administration attenuated the AAC-induced atrial remodeling that was aggravated by SPX. CONCLUSION: The study results suggest that SPX exacerbates AAC-induced inflammatory atrial fibrosis and increases vulnerability to AF after 4 weeks, likely because of depletion of spleen-derived IL-10. PMID- 26144347 TI - Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas' disease. AB - Inhibition of the cysteine protease cruzain from Trypanosoma cruzi has been studied pre-clinically as a new chemotherapeutic approach to treat Chagas' disease. Efficacious effects of vinylsulfone-based cruzain inhibitors in animal models support this therapeutic hypothesis. More recently, substrate-activity screening was used to identify nonpeptidic tetrafluorophenoxymethyl ketone inhibitors of cruzain that showed promising efficacy in animal models. Herein we report efforts to further optimize the in vitro potency and in vivo pharmacokinetic properties of this new class of cruzain inhibitors. Through modifications of the P1, P2 and/or P3 positions, new analogs have been identified with reduced lipophilicity, enhanced potency, and improved oral exposure and bioavailability. PMID- 26144349 TI - Genetic purgatory and the cardiac channelopathies: Exposing the variants of uncertain/unknown significance issue. AB - Merriam-Webster's online dictionary defines purgatory as "an intermediate state after death for expiatory purification" or more specifically as "a place or state of punishment wherein according to Roman Catholic doctrine the souls of those who die in God's grace may make satisfaction for past sins and so become fit for heaven." Alternatively, it is defined as "a place or state of temporary suffering or misery." Either way, purgatory is a place where you are stuck, and you don't want to be stuck there. It is in this context that the term genetic purgatory is introduced. Genetic purgatory is a place where the genetic test-ordering physician and patients and their families are stuck when a variant of uncertain/unknown significance (VUS) has been elucidated. It is in this dark place where suffering and misery are occurring because of unenlightened handling of a VUS, which includes using the VUS for predictive genetic testing and making radical treatment recommendations based on the presence or absence of a so-called maybe mutation. Before one can escape from this miserable place, one must first recognize that one is stuck there. Hence, the purpose of this review article is to fully expose the VUS issue as it relates to the cardiac channelopathies and make the cardiologists/geneticists/genetic counselors who order such genetic tests believers in genetic purgatory. Only then can one meaningfully attempt to get out of that place and seek to promote a VUS to disease-causative mutation status or demote it to an utterly innocuous and irrelevant variant. PMID- 26144350 TI - Prospective, multicenter validation of a clinical risk score for left atrial arrhythmogenic substrate based on voltage analysis: DR-FLASH score. AB - BACKGROUND: Left atrial (LA) low-voltage areas (LVAs) are frequently observed in patients with atrial fibrillation (AF) and may predict AF recurrence after catheter ablation. OBJECTIVE: The aim of this study was to develop and validate a clinical tool to identify LVAs that are associated with AF recurrence after pulmonary vein isolation (PVI). METHODS: In a cohort of 238 patients, voltage maps were created during LA procedures. LVAs were defined as areas with electrogram amplitudes <0.5 mV. On the basis of regression analysis, predictors of LA substrate were identified. These parameters were used to establish a dedicated risk score (DR-FLASH score, based on diabetes mellitus, renal dysfunction, persistent form of AF, LA diameter >45 mm, age >65 years, female sex, and hypertension). This risk score was then prospectively validated in a multicenter cohort of 180 patients. The association of the score with long-term recurrence of atrial arrhythmias after circumferential PVI was tested in a retrospective cohort of 484 patients. RESULTS: The DR-FLASH score effectively identified LVA substrate (C statistic = 0.801, P < .001). In the prospective multicenter validation cohort, the predictive value of the DR-FLASH score was confirmed (C statistic = 0.767, P < .001). The probability for the presence of LA substrate increased by a factor of 2.2 (95% confidence interval [CI] 1.6-2.9, P < .001) with each point scored. Furthermore, the risk of AF recurrence after PVI increased by a factor of 1.3 (95% CI 1.1-1.5, P < .001) with every additional point and was almost 2 times higher in patients with a DR-FLASH score >3 (odds ratio 1.7, 95% CI 1.1-2.8, P = .026). CONCLUSION: The DR-FLASH score may be useful to identify patients who may require extensive substrate modification instead of PVI alone. PMID- 26144351 TI - Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction. AB - Vascular endothelial growth factor (VEGF) promotes angiogenesis and improves cardiac function after myocardial infarction (MI). However, the non-targeted delivery of VEGF decreases its therapeutic efficacy due to an insufficient local concentration in the ischemic myocardium. In this study, we used a specific peptide to modify VEGF and determined that this modified VEGF (IMT-VEGF) localized to the ischemic myocardium through intravenous injection by interacting with cardiac troponin I (cTnI). When IMT-VEGF was used to mediate cardiac repair in a rat model of ischemia-reperfusion (I-R) injury, we observed a decreased scar size, enhanced angiogenesis and improved cardiac function. Moreover, an alternative treatment using the repeated administration of a low-dose IMT-VEGF also promoted angiogenesis and functional recovery. The therapeutic effects of IMT-VEGF were further confirmed in a pig model of MI as the result of the conserved properties of its interacting protein, cTnI. These results suggest a promising therapeutic strategy for MI based on the targeted delivery of IMT-VEGF. PMID- 26144367 TI - 'Facing the wrong way': Exploring the Occipito Posterior position/back pain discourse from women's and midwives perspectives. AB - OBJECTIVE: to explore back pain in labour from the perspectives of women and midwives. DESIGN: a qualitative study, which generated data through individual semi-structured interviews with postnatal women and focus groups with midwives. Data were analysed thematically. SETTING: two metropolitan maternity units in Queensland, Australia. PARTICIPANTS: nine postnatal women and 11 midwives, all of whom had participated in a randomized controlled trial investigating the use of sterile water injections for back pain in labour. FINDINGS: two major themes were identified, including back pain in labour: accounts, rationalisations and coping strategies, and fetal position: destabilising the Occipito Posterior-back pain discourse. KEY CONCLUSIONS: back pain may be severe in labour, may impact negatively upon women's labour and birth experiences, and interfere with their ability to cope as planned. The assumed relationship between fetal position and back pain in labour is a dominant discourse, albeit one which is lacking in empirical credibility. Nonetheless, the information provided to women by maternity professionals tended to reiterate customary practices and beliefs rather than factual knowledge. Increasingly, women refer to other sources, which may challenge the information provided by health professionals. IMPLICATIONS FOR PRACTICE: Back pain in labour is an under-researched area and the lack of solid evidence underpinning the advice provided to women has implications for labour management, and possibly for maternal and fetal outcomes. Care providers might usefully consider back pain as multifactorial, not always associated with OP position, and continue to seek evidence-based management strategies which address women's needs. PMID- 26144368 TI - Job satisfaction and retention of midwives in rural Nigeria. AB - BACKGROUND: Nigeria is one of the 57 countries with a critical shortage of human resources for health, especially in remote rural areas and in northern states. The National Midwifery Service Scheme (MSS) is one approach introduced by the Government of Nigeria to address the health workforce shortage in rural areas. Since 2009, unemployed, retired and newly graduated midwives are deployed to primary health care (PHC) facilities in rural areas of Nigeria. These midwives form the mainstay of the health system at the primary health care level especially as it relates to the provision of skilled attendance at birth. This study followed up and explored the job satisfaction and retention of the MSS midwives in three Northern states of Nigeria. METHODS: this was a descriptive study. Data were collected using a mixed method approach which included a job satisfaction survey, focus group discussions (FGDs) and exit interviews to explore job satisfaction and retention factors. All 119 MSS midwives deployed by the National Primary Health Care Development Agency between 2010 and 2012 to the 51 Partnership for Reviving Routine Immunisation- Maternal and Child Health (PRRINN-MNCH) programme targeted PHC facilities were included in the study. RESULTS: MSS midwives were very satisfied with from the feeling of caring for women and children in the community (4.56), with the chance to help and care for others (Mean 4.50), the feeling of worthwhile accomplishment from doing the job (Mean 4.44) and the degree of respect and fair treatment they received from more senior staff and/or supervisor (Mean 4.39). MSS midwives were least satisfied with the lack of existence of a (established) career ladder (Mean 2.5), availability of promotional opportunities within the scheme (Mean 2.66), safety of accommodation (Mean 3.18), and with 'the degree to which they were fairly paid for what they contribute to the health facility' (Mean 3.41). When asked about future career plans, 38% (n=33) of the MSS midwives planned to leave the scheme within two years, of which 16 (18%) wanted to leave within one year. However, 39% of the midwives (n=34) indicated that they would be happy to continue working even after the scheme has ended. Of these 34 participants, 18 would like to continue working in the same facility where they are now whereas the remaining 16 would like to continue working in the north but not in the facility where they are working currently. Eight themes on job satisfaction and retention emerged from the FGDs conducted with current midwives, whereas six themes emerged from the exit interviews from midwives who have left the scheme. CONCLUSION: the MSS programme is a short-term solution to increase SBA coverage in rural Nigeria. MSS midwives were dissatisfied with the short term contract, lack of career structure, irregular payment, poor working condition, inadequate supervision and poor accommodation being offered by the programme, which all contribute to poor retention of MSS midwives. IMPLICATIONS FOR POLICY AND PRACTICE: midwives' job satisfaction and retention are critical to improving the health of mothers and their newborn. Poor job satisfaction and retention therefore requires improvements in financial and non-financial incentives, health systems, supportive supervision, ensuring job security and a career structure for midwives working in rural health facilities. Initiating effective strategies to motivate and increase the retention of rural health workers is important for Nigeria to achieve the Millennium/Sustainable Development Goals. PMID- 26144369 TI - The effect of rheological behavior and microstructure of the emulgels on the release and permeation profiles of Terpinen-4-ol. AB - Terpinen-4-ol, the main component of Australian tea tree oil, which was widely used in pharmaceutical and cosmetic fields, was chosen as the active component in this study because of its excellent antimicrobial properties and good permeability. The objective of this study was to investigate the relationships between rheological characters, in vitro release and permeation profiles of the emulgels. Particle size distribution, optical microscopy tests were performed to characterize the status of the emulgels. Scanning electron microscopy and rheology tests were carried out to assess the strength of the structures. In vitro release and percutaneous permeation study of Terpinen-4-ol through Cellophane(r) membrane and excised rabbit skin were conducted by vertical Franz diffusion cell, respectively. All of the emulgel samples showed a non-uniform bimodal distribution and the microstructure represented a matrix type which could inhibit the diffusion of oil droplets in formulation in some extent. Rheological data showed a good fit to the Herschel-Bulkley model in viscosimetric studies regardless of the polymers used. Moreover, 10% Sepiplus 400 had obtained the highest zero-shear viscosity, G', G" value and lowest tau95%G' value corresponding to the strongest structure. The results of in vitro release tests revealed that an increase in viscosity may affect the release profiles inversely, irrespective of the polymers used. In vitro permeation of Terpinen-4-ol tests indicated that when the drug amount released could satisfy the essential driving force, permeation processes was independent of release. In contrast, the drug amount released could not satisfy the essential driving force, the permeation amount was inversely proportional to the viscosity as the release amount did. PMID- 26144370 TI - Fibroblast growth factor 21 prevents glycemic deterioration in insulin deficient mouse models of diabetes. AB - In type 1 diabetes, there is a rapid loss of glycemic control immediately after onset of the disease. We aimed to determine if the deterioration of glycemic control that occurs early after the onset of insulin-deficient diabetes could be blunted by treatment with recombinant fibroblast growth factor 21 (FGF21). Normal C57BL/6J mice made diabetic by a single high dose injection of streptozotocin (STZ) were randomized to receive twice daily subcutaneous injection of vehicle or recombinant human FGF21 at doses of 0.3 and 1.0 mg/kg for 10 days. Body weight was recorded daily and 5 h fasted glucose, insulin, glucagon, free fatty acids and ketones were determined at 6 and 10 days post-randomization. The increase in fasting plasma glucose induced by STZ in untreated mice was prevented with FGF21 at 0.3 mg/kg BID. In contrast, at 1.0 mg/kg BID, FGF21 did not prevent the rise in plasma glucose after STZ. At the end of the study, plasma glucagon was significantly higher in the diabetic group treated with FGF21 1.0 mg/kg BID than in the untreated group. This was not seen for the group treated with FGF21 0.3 mg/kg BID. There were significant dose dependent reductions in plasma free fatty acids with FGF21 treatment but no significant change in plasma ketones (beta hydroxybutyrate). FGF21 treatment did not have significant effects on body weight in lean insulin deficient mice. In conclusion, FGF21 prevents increases in glycaemia and has lipid lowering properties in mouse models of insulin deficient diabetes, although by increasing the dose increased glucagon levels are seen and hyperglycemia persists. PMID- 26144371 TI - Bench-to-bedside pharmacology of adrenomedullin. AB - The bioactive peptide adrenomedullin (AM) exerts pleiotropic actions in various organs and tissues. In the heart, AM has an inhibitory effect on ventricular remodeling, suppressing cardiomyocyte hypertrophy and the proliferation of cardiac fibroblasts. This pharmacological property was shown not only in rat models of acute myocardial infarction, but also clinically in patients with this cardiac disease. An originally characterized feature of AM was a potent vasodilatory effect, but this peptide was found to be important for vascular integrity and angiogenesis. AM-induced angiogenesis is involved in tumor growth, while AM inhibits apoptosis of some types of tumor cell. A unique pharmacological property is anti-inflammatory activity, which has been characterized in sepsis and inflammatory bowel diseases; thus, there is an ongoing clinical trial to test the efficacy of AM for patients with intractable ulcerative colitis. These activities are assumed to be mediated via the specific receptor formed by calcitonin receptor-like receptor and receptor activity-modifying protein 2 or 3, while some questions remain to be answered about the molecular mechanisms of this signal transduction system. Taking these findings together, AM is a bioactive peptide with pleiotropic effects, with potential as a therapeutic tool for a wide range of human diseases from myocardial infarction to malignant tumors or inflammatory bowel diseases. PMID- 26144372 TI - Semaphorin 7A plays a critical role in IgE-mediated airway inflammation in mice. AB - Elevated allergen-specific IgE levels are a hallmark of allergic asthma, a disease involving chronic airway inflammation characterized by airway hyperresponsiveness (AHR); neutrophilic airway inflammation is found in patients with severe asthma. Furthermore, we have reported that interleukin (IL)-33 and IL 17A contribute to IgE-mediated AHR through neutrophilic inflammation in mice. Meanwhile, semaphorins regulating neuronal and immune function have been focused on in several diseases. Here, we investigated whether semaphorin 7A (SEMA7A) is related to IgE-mediated neutrophilic inflammation in mice. BALB/c mice sensitized with antigen-specific IgE monoclonal antibody were repeatedly challenged by the antigen. When anti-SEMA7A antibody was administered during the fourth to seventh challenges, the infiltration by macrophages, lymphocytes, neutrophils, and eosinophils in the lungs was reduced at the seventh challenge (P<0.05, 0.05, 0.01, and 0.05, respectively). However, the increased production of IL-4, IL-5, IL-13, IL-33, IL-17A, IL-6, and CXCL1 in the lungs was not suppressed. In histological analysis, the epithelial cells, blood vessels, and inflammatory cells in the lungs of IgE-sensitized mice showed SEMA7A expression; plexin C1 for the receptor was expressed in the inflammatory cells. Meanwhile, we examined the effect of anti-SEMA7A antibody on AHR and neutrophilic inflammation enhanced by the collaborative action of IL-33 and IL-17A in normal mice, resulting in the suppression of these responses (P<0.05 and 0.01, respectively). Collectively, we demonstrated that SEMA7A plays a critical role in IgE-mediated neutrophilic airway inflammation. Therefore, SEMA7A may be a potential therapeutic target for severe allergic asthma showing neutrophilic airway inflammation. PMID- 26144373 TI - The vasorelaxant effect of 8(17),12E,14-labdatrien-18-oic acid involves stimulation of adenylyl cyclase and cAMP/PKA pathway: Evidences by pharmacological and molecular docking studies. AB - The relaxant effect of 8(17),12E,14-labdatrien-18-oic acid (LBD) was investigated on isolated aortic rings and compared with forskolin (FSK), a standard and potent activator of adenylyl cyclase (AC) with relaxing effect. The presence of potassium channel blockers, such as glibenclamide (ATP-blocker), apamin (SKCa blocker), charybdotoxin (BKCa-blocker) did not significantly affect either the LBD or FSK concentration-response curves. However, in the presence of 4 aminopyridine (KV-blocker), the relaxant effect for both diterpenes was significantly attenuated, with reduction of its relative potencies. Moreover, the relaxation induced by 8-Br-cAMP, an analog of cAMP, was also significantly attenuated in the same conditions, i.e., in the presence of 4-aminopyridine. The presence of aminophylline, a nonselective phosphodiesterase inhibitor, caused a significant increasing in the potency for both LBD and FSK. On the other hand, the presence of Rp-cAMPS, a selective PKA-inhibitor, significantly attenuated the relaxant effect of LBD. In this work, in the same experimental conditions, both labdane-type diterpenes presented remarkably similar results; FSK, however, presented a higher potency (100-fold) than LBD. Thus, the hypothesis that LBD could be a novel AC-activator emerged. To assess that hypothesis, computational molecular docking studies were performed. Crystallographic structure of adenylyl cyclase/forskolin complex (1AB8) was obtained from RSCB Protein Data Bank and used to compare the modes of interaction of the native ligand and LBD. The computational data shows many similarities between LBD and FSK concerning the interaction with the regulatory site of AC. Taken together, the results presented here pointed to LBD as a novel AC-activator. PMID- 26144374 TI - Nesfatin-1 signaling in the basom edial amygdala modulates the gastric distension sensitive neurons discharge and decreases gastric motility via melanocortin 3/4 receptors and modified by the arcuate nucleus. AB - Nesfatin-1 is a novel anorexigenic peptide that regulates feeding behavior and gastrointestinal function. This study aimed to explore the effects of nesfatin-1 on gastric distension (GD)-sensitive neurons in the basomedial amygdala (BMA) and the potential mechanism for nesfatin-1 to regulate gastric motility through the arcuate nucleus (Arc). The projection of nerve fiber and expression of nesfatin-1 were observed by retrograde tracing and fluo-immunohistochemistry staining. Single-unit discharges in the BMA were recorded extracellularly, and gastric motility in conscious rats was monitored. Results showed that the nesfatin-1/ fluorogold-double labeled neurons were observed in the Arc. Nesfatin-1 could excite the GD-excitatory neurons and inhibit the GD-inhibitory neurons in the BMA. Gastric motility and gastric emptying were significantly reduced by nesfatin 1 administration to the BMA in a dose-dependent manner. The effects of nesfatin-1 could be partially blocked by melanocortin 3/4 receptors antagonist, SHU9119. Electrical stimulation of the Arc significantly excited the response of GD neurons to nesfatin-1 and promoted gastric motility. Nevertheless, these effects could be mitigated by pretreatment with anti-NUCB2/nesfatin-1 antibody. It is suggested that nesfatin-1 in the BMA plays an important role in decreasing gastric motility and the Arc may be involved in this regulation process. PMID- 26144375 TI - MAS receptors mediate vasoprotective and atheroprotective effects of candesartan upon the recovery of vascular angiotensin-converting enzyme 2-angiotensin-(1-7) MAS axis functionality. AB - AT1 antagonists effectively prevent atherosclerosis since AT1 upregulation and angiotensin II-induced proinflammatory actions are critical to atherogenesis. Despite the classic mechanisms underlying the vasoprotective and atheroprotective actions of AT1 antagonists, the cross-talk between angiotensin-converting enzyme angiotensin II-AT1 and angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axes suggests other mechanisms beyond AT1 blockage in such effects. For instance, angiotensin-converting enzyme 2 activity is inhibited by reactive oxygen species derived from AT1-mediated proinflammatory signaling. Since angiotensin-(1-7) promotes antiatherogenic effects, we hypothesized that the vasoprotective and atheroprotective effects of AT1 antagonists could result from their inhibitory effects on the AT1-mediated negative modulation of vascular angiotensin converting enzyme 2-angiotensin-(1-7)-MAS axis functionality. Interestingly, our results showed that early atherosclerosis triggered in thoracic aorta from high cholesterol fed-Apolipoprotein E-deficient mice impairs angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality by a proinflammatory-redox AT1 mediated pathway. In such mechanism, AT1 activation leads to the aortic release of tumor necrosis factor-alpha, which stimulates NAD(P)H oxidase/Nox1-driven generation of superoxide and hydrogen peroxide. While hydrogen peroxide inhibits angiotensin-converting enzyme 2 activity, superoxide impairs MAS functionality. Candesartan treatment restored the functionality of angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis by inhibiting the proinflammatory-redox AT1-mediated mechanism. Candesartan also promoted vasoprotective and atheroprotective effects that were mediated by MAS since A779 (MAS antagonist) co-treatment inhibited them. The role of MAS receptors as the final mediators of the vasoprotective and atheroprotective effects of candesartan was supported by the vascular actions of angiotensin-(1-7) upon the recovery of the functionality of vascular angiotensin converting enzyme 2-angiotensin-(1-7)-MAS axis. PMID- 26144376 TI - The effects of polyamines on human colonic mucosal function. AB - Electrogenic ion transport in human colon is a surrogate marker for colonic mucosal function, and may be manipulated by a variety of hormonal, neural, immune and paracrine mediators. Polyamines are present in vast quantities in the colonic lumen and appear to be integral to cellular function. This study explores some of the mechanisms of polyamine action on colonic tissue through study of their effects on differential secretory pathways, as well as examining their actions on intracellular cAMP and Ca(2+) accumulation. Human colonic mucosa was mounted in Ussing chambers and treated with polyamines (spermine, spermidine and putrescine) with changes in ion transport recorded. In separate experiments colonic crypts were treated with polyamines and intracellular cAMP levels determined by ELISA and intracellular calcium concentrations were quantified by fluorescent imaging. Polyamines at physiological concentrations (1mM) exert no effects on basal mucosal chloride secretion or transepithelial electrical resistance. Polyamines inhibit electrogenic ion secretion as stimulated by forskolin (cAMP-mediated), but not carbachol (Ach-mediated). All the polyamines used in this study inhibited intracellular cAMP accumulation, according to potency (spermine>spermidine>putrescine). Spermine increased intracellular Ca(2+) in a PKC-dependent manner, likely due to its effects on the extracellular calcium sensing receptor (CaSR). Polyamines act to prevent cAMP-mediated Cl(-) hypersecretion in the colon, acting through CaSR to inhibit PKC-mediated [Ca(2+)]i release from intracellular stores. PMID- 26144377 TI - Physcion induces mitochondria-driven apoptosis in colorectal cancer cells via downregulating EMMPRIN. AB - Physcion, an anthraquinone derivative widely isolated and characterized from both terrestrial and marine sources, has anti-tumor effects on a variety of carcinoma cells, mainly through inhibition of cell proliferation, apoptosis induction and cell cycle arrest. However, little is known about the mechanisms underlying its role in tumor progression. In the present study, we investigated the molecular mechanisms involved in physcion-induced apoptosis in human colorectal cancer (CRC) lines HCT116. Our results showed that physcion inhibited tumor cell viability in a dose- and time-dependent manner, and induced cell apoptosis via intrinsic mitochondrial pathway. Our results also revealed that physcion treatment significantly inhibited extracelluar matrix metalloproteinase inducer (EMMPRIN) expression in HCT116 cells in a dose-dependent manner and overexpression of EMMPRIN protein markedly reduced physcion-induced cell apoptosis. Furthermore, our results strongly indicated the modulating effect of physcion on EMMPRIN is correlated with AMP-activated protein kinase (AMPK)/Hypoxia-inducible factor 1alpha (HIF-1alpha) signaling pathway. Our data provide the first experimental evidence that physcion induces mitochondrial apoptosis in CRC cells by downregulating of EMMPRIN via AMPK/HIF-1alpha signaling pathway and suggest a new mechanism to explain its anti-tumor effects. PMID- 26144387 TI - DFT-B3LYP computations of electro and thermo molecular characteristics and mode of action of fungicides (chlorophenols). AB - Density functional theoretical (DFT) calculations of the pesticides; 2 chlorophenol (2-CP), 2,4,6-trichlorophenol (TCP) and pentachlorophenol (PCP) have been carried out using 6-311++G** basis set available on Gaussian-09 software in order to optimize the molecular structures. The optimized geometry of the molecules has been found to possess Cs symmetry. The charge transfer phenomena occurring in the molecules have been exhibited by (HOMO-LUMO) analysis. The molecular ESP values and mappings of electron density iso-surface with the molecular electrostatic potential (MEP), have been carried out to achieve the information of the size, shape, charge density distribution and site of chemical reactivity of the molecules. Thermo molecular characteristics have been computed to achieve essential environmental influence on the activities of fungicides. PMID- 26144388 TI - Child development and maternal wellbeing: family perspectives for low-income and middle-income countries. PMID- 26144389 TI - Effects of a parenting intervention to address maternal psychological wellbeing and child development and growth in rural Uganda: a community-based, cluster randomised trial. AB - BACKGROUND: Parenting interventions have been implemented to improve the compromised developmental potential among 39% of children younger than 5 years living in low-income and middle-income countries. Maternal wellbeing is important for child development, especially in children younger than 3 years who are vulnerable and dependent on their mothers for nutrition and stimulation. We assessed an integrated, community-based parenting intervention that targeted both child development and maternal wellbeing in rural Uganda. METHODS: In this community-based, cluster randomised trial, we assessed the effectiveness of a manualised, parenting intervention in Lira, Uganda. We selected and randomly assigned 12 parishes (1:1) to either parenting intervention or control (inclusion on a waitlist with a brief message on nutrition) groups using a computer generated list of random numbers. Within each parish, we selected two to three eligible communities that had a parish office or a primary school in which a preschool could be established, more than 75 households with children younger than 6 years, and at least 15 socially disadvantaged families (ie, maternal education of primary school level or lower) with at least one child younger than 36 months. Participants within communities were mother-child dyads, where the child was 12-36 months of age at enrollment, and the mother had low maternal education. In the parenting intervention group, participants attended 12 fortnightly peer-led group sessions focusing on child care and maternal wellbeing. The primary outcomes were cognitive and receptive language development, as measured with the Bayley Scales of Infant Development, 3rd edn. Secondary outcomes included self-reported maternal depressive symptoms, using the Center for Epidemiologic Studies Depression Scale, and child growth. Theoretically-relevant parenting practices, including the Home Observation for Measurement of the Environment inventory, and mother-care variables, such as perceived spousal support, were also assessed as potential mediators. Baseline assessments were done in January, 2013, and endline assessments were done in November, 2013, 3 months after completion of the programme. Ethics approval was received from Mbarara and McGill universities. This trial is registered with ClinicalTrials.gov, NCT01906606. FINDINGS: Between December, 2012, and January, 2013, 13 communities (194 dyads) were randomly assigned to receive intervention, and 12 communities (154 dyads) were assigned to a waitlist control. 319 dyads completed baseline measures (171 in the intervention group and 148 in the control group), and 291 dyads completed endline measures (160 in the intervention group and 131 in the control group). At endline, children in the intervention group had significantly higher cognitive scores (58.90 vs 55.65, effect size 0.36, 95% CI 0.12-0.59) and receptive language scores (23.86 vs 22.40, 0.27, 0.03-0.50) than did children in the control group. Mothers in the intervention group reported significantly fewer depressive symptoms (15.36 vs 18.61, -0.391, 95% CI -0.62 to 0.16) than did mothers in the control group. However, no differences were found in child growth between groups. INTERPRETATION: The 12 session integrated parenting intervention delivered by non-professional community members improved child development and maternal wellbeing in rural Uganda. Because this intervention was largely managed and implemented by a local organisation, using local community members and minimal resources, such a programme has the potential to be replicated and scaled up in other low-resource, village-based settings. FUNDING: Plan Uganda via Plan Finland (Ministry of Foreign Affairs) and Plan Australia (Australian Aid). PMID- 26144412 TI - Surgical speed and risk for maternal operative morbidity in emergent repeat cesarean delivery. AB - OBJECTIVE: The purpose of this study was to determine whether surgical speed is associated with maternal outcomes in women who have a history of previous cesarean delivery (CD) and who require emergent delivery. STUDY DESIGN: This is a secondary analysis of a multicenter, prospective observational study of women with a history of previous CD. Women who attempted a vaginal birth after CD and required emergent CD were dichotomized into those with a skin incision-to-fetal delivery time of <=2 min (I-D <=2) or >2 min (I-D >2), based on the mode I-D. Rates of composite maternal complications and specific surgical complications were compared. RESULTS: Seven hundred ninety-three women had an emergency repeat CD: 108 women (13.6%) had I-D <=2, and 685 women (86.4%) had I-D >2. The composite of maternal morbidity occurred in 36% of women with I-D<=2 and 23% with I-D>2 (P < .01). Women with I-D <=2 had higher odds of intraoperative transfusion, uterine artery ligation, and broad ligament hematoma. In a multivariable regression model, the only variable that remained associated with maternal outcome was I-D (relative risk, 1.66; 95% confidence interval, 1.23 2.23). There was no difference in the incidence of neonatal acidemia between groups. CONCLUSION: Among women who underwent emergent repeat cesarean delivery, surgical speed was associated with an increased risk for maternal complications. PMID- 26144453 TI - Clinical Profile of Patients With High-Risk Tako-Tsubo Cardiomyopathy. AB - Although tako-tsubo cardiomyopathy (TTC) is regarded as a reversible condition with favorable outcome, a malignant clinical course evolves in some subjects. In this single-institution experience, we describe the clinical profile of patients with adverse TTC outcome. A cohort of 249 consecutive patients with TTC was interrogated for those with acute unstable presentation during the first 24 hours. Forty-seven patients (19%) experienced early complicated clinical course with cardiac arrest in 9 (ventricular fibrillation, n = 4, pulseless electrical activity, n = 3, and asystole, n = 2) or marked hypotension in 38 (systolic blood pressure <=90 mm Hg requiring vasopressors and/or balloon pump). Of the 47 patients, Killip class III to IV heart failure was present in 30 (64%). Despite treatment, 8 patients (3%; all women) died inhospital due to respiratory failure, cardiogenic shock, or anoxic brain injury. All 8 inhospital deaths occurred among the 47 patients with unstable presentation, including 2 after cardiac arrest and 6 with marked hypotension. Post-TTC event mortality for a period of 4.7 +/- 3.4 years significantly exceeded that in a matched general US population (standardized mortality ratio 1.4; 95% confidence interval 1.1 to 1.9; p = 0.005) largely due to noncardiac co-morbidities. In conclusion, contrary to widespread perception, TTC is not an entirely benign and reversible condition. Among this large cohort, a high-risk subgroup was identified with cardiac arrest or hemodynamic instability, accounting for all hospital deaths. Hospital nonsurvivors had a variety of irreversible co-morbid conditions with the potential to compromise clinical status and adversely affect short-term survival. Long-term survival after hospital discharge was also reduced compared with the general population because of noncardiac co-morbidities. PMID- 26144489 TI - Circadian phenotyping of obese and diabetic db/db mice. AB - Growing evidence links metabolic disorders to circadian alterations. Genetically obese db/db mice, lacking the long isoform of leptin receptor, are a recognized model of type 2 diabetes. In this study, we aimed at characterizing the potential circadian alterations of db/db mice in comparison to db/+ control mice. By using telemetry devices, we first reported arrhythmicity in general activity of most db/db mice under both light-dark cycle and constant darkness, while their rhythm of body temperature is less dramatically disrupted. Water access restricted to nighttime restores significant rhythmicity in behaviorally arrhythmic db/db mice, indicating a masking effect of polydipsia when water is available ad libitum. Endogenous period of temperature rhythm under constant dark conditions is significantly increased (+30 min) in db/db compared with db/+ mice. Next, we studied the oscillations of clock proteins (PER1, PER2 and BMAL1) in the suprachiasmatic nuclei (SCN), the site of the master clock, and detected no difference according to the genotype. Furthermore, c-FOS and P-ERK1/2 expression in response to a light pulse in late night was significantly increased (+80 and +55%, respectively) in the SCN of these diabetic mice. We previously showed that, in addition to altered activity rhythms, db/db mice exhibit altered feeding rhythm. Therefore, we investigated daily patterns of clock protein expression in medial hypothalamic oscillators involved in feeding behavior (arcuate nucleus, ventro- and dorso-medial hypothalamic nuclei). Compared with db/+ mice, very subtle or no difference in oscillations of PER1 and BMAL1 is found in the medial hypothalamus. Although we did not find a clear link between altered hypothalamic clockwork and behavioral rhythms in db/db mice, our results highlight a lengthened endogenous period and altered photic integration in these genetically obese and diabetic mice. PMID- 26144504 TI - Multimorbidity among people with HIV in regional New South Wales, Australia. AB - Background Multimorbidity is the co-occurrence of more than one chronic health condition in addition to HIV. Higher multimorbidity increases mortality, complexity of care and healthcare costs while decreasing quality of life. The prevalence of and factors associated with multimorbidity among HIV positive patients attending a regional sexual health service are described. METHODS: A record review of all HIV positive patients attending the service between 1 July 2011 and 30 June 2012 was conducted. Two medical officers reviewed records for chronic health conditions and to rate multimorbidity using the Cumulative Illness Rating Scale (CIRS). Univariate and multivariate linear regression analyses were used to determine factors associated with a higher CIRS score. RESULTS: One hundred and eighty-nine individuals were included in the study; the mean age was 51.8 years and 92.6% were men. One-quarter (25.4%) had ever been diagnosed with AIDS. Multimorbidity was extremely common, with 54.5% of individuals having two or more chronic health conditions in addition to HIV; the most common being a mental health diagnosis, followed by vascular disease. In multivariate analysis, older age, having ever been diagnosed with AIDS and being on an antiretroviral regimen other than two nucleosides and a non-nucleoside reverse transcriptase inhibitor or protease inhibitor were associated with a higher CIRS score. CONCLUSION: To the best of our knowledge, this is the first study looking at associations with multimorbidity in the Australian setting. Care models for HIV positive patients should include assessing and managing multimorbidity, particularly in older people and those that have ever been diagnosed with AIDS. PMID- 26144505 TI - Towards deep-UV surface-enhanced resonance Raman spectroscopy of explosives: ultrasensitive, real-time and reproducible detection of TNT. AB - We report ultrasensitive and label-free detection of 2,4,6-trinitrotoluene (TNT) deposited by drop coating using deep-ultraviolet surface-enhanced resonance Raman scattering (DUV-SERRS). Well-defined aluminum nanoparticle arrays as the SERRS substrate at 257 nm excitation wavelength enabled highly reproducible and real time detection of TNT down to the detection limit of the attogram level in quantity. This extreme sensitivity can be further improved by optimization of the nanostructured substrates. DUV-SERRS promises to have a large impact on public safety and security, as it can be readily extended to other explosives and hazardous materials. PMID- 26144506 TI - [An expression of our practice, our life]. PMID- 26144507 TI - [Caring for the cirrhotic patient]. PMID- 26144508 TI - [The complex management of cirrhosis patients]. AB - All chronic liver diseases, whatever their causes, can lead to cirrhosis, when they evolve untreated for more than 10 to 20 years. The diagnosis of cirrhosis is based on the histology obtained from a liver biopsy, or on composite scores or elasticity. While these indirect tests are approved they are only reimbursed for viral hepatitis C associated or not with HIV. PMID- 26144509 TI - [Diagnosis and initial assessment of cirrhosis]. AB - When it is compensated, cirrhosis is usually asymptomatic meaning that many people with the disease are unaware they have it. It is however essential to establish with certainty the cirrhosis diagnosis as the condition is responsible for a number of complications such as liver cancer (most frequently hepatocellular carcinoma), gastrointestinal bleeding or severe liver failure. Knowledge of the diagnosis ensures the prevention, screening and early treatment of these complications. PMID- 26144510 TI - [Cirrhosis and its complications]. AB - The treatment of cirrhosis is based partly on the treatment of the causes and partly on the prevention and treatment of the complications. In cases of serious, life-threatening illness, a transplant must be envisaged. PMID- 26144511 TI - [Management of patients with TIPS]. AB - The Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure is now performed in almost twenty hospitals in France, including Tours university hospital. The aim is to reduce portal hypertension (PHT) by diverting the portal system to the caval system within the liver. The main cause of PHT is cirrhosis, which may be of alcoholic, viral, dysmetabolic or autoimmune origin. PMID- 26144512 TI - [Liver transplantation]. AB - The liver transplant procedure has advanced significantly since the 1960s. It is the only curative treatment for severe chronic liver disease including cirrhosis. In collaboration with the French Biomedicine Agency, a complex protocol is put in place by a multi-disciplinary team. The patient's commitment to the treatment project is essential. PMID- 26144513 TI - [The transport nurse]. AB - Caring, reassuring, supporting and repatriating people in medical distress from anywhere in the world: such is the day-to-day work of the repatriation nurses at Mondial Assistance. Ludovic Le Gal has been doing this job for the last eleven years with a passion which has remained undiminished. PMID- 26144514 TI - [Figurines for teaching disaster medicine]. AB - The teaching of collective risks to paramedical staff is a difficult exercise. To make the training more concrete, the team from the emergency care training centre at Rouen university hospital has adopted an innovative pedagogical approach. Based on a multi-casualty disaster scenario and using model figures, the training invites participants to take part in role plays. PMID- 26144515 TI - [An advanced nurse practitioner in general medicine in the United Kingdom]. AB - In the United Kingdom, an advanced nurse practitioner can carry out consultations and write prescriptions in the same way as a general practitioner. Jenny Aston, a nurse for more than 30 years, works in a GP surgery in Cambridge. Here, she explains the role of nurses in the organisation of health care in the UK, and talks about her career and her missions as an advanced nurse practitioner. PMID- 26144516 TI - [Doctor-nurse delegation of the insertion of central venous lines]. AB - The Leon Berard Cancer Centre treats the disease in all its complexity with numerous disciplines such as surgery, medicine, radiotherapy, palliative care, home care, etc. The insertion of a central venous line is an essential part of cancer care and the nursing profession. It enables patients to have their treatment administered in the best possible conditions and without risk. PMID- 26144517 TI - [The admission interview in addictology, nursing practices and skills]. AB - The reception of a patient in addictology determines how the care will proceed. The setting up of nurse-patient admission interviews adapted to the request for addiction treatment helps professionals meet the patients' needs in terms of listening, guidance, consideration and care. How should the nurse approach this call for help, this "desire" or this necessity for addicted patients to get help? What skills does she need to use? PMID- 26144518 TI - [Traditional Chinese medicine and cancer recurrence]. AB - Being diagnosed with cancer and having to undergo gruelling treatment is an ordeal. A recurrence of the disease is equally traumatic and can have a profound impact on the patient's balance. In this context, traditional Chinese medicine can strengthen vitality and help to improve the patient's quality of life. PMID- 26144519 TI - Common winter viruses. PMID- 26144520 TI - [Dealing with the violent patient]. PMID- 26144521 TI - [Treatment of diabetes with an insulin pump]. PMID- 26144522 TI - [Nursing students: authors and players of hospital quality]. PMID- 26144523 TI - [Nurse's role of the culture and microbiological examination of mucus]. PMID- 26144524 TI - Energetics and carrier transport in doped Si/SiO2 quantum dots. AB - In the present theoretical work we have considered impurities, either boron or phosphorous, located at different substitutional sites in silicon quantum dots (Si-QDs) with diameters around 1.5 nm, embedded in a SiO2 matrix. Formation energy calculations reveal that the most energetically-favored doping sites are inside the QD and at the Si/SiO2 interface for P and B impurities, respectively. Furthermore, electron and hole transport calculations show in all the cases a strong reduction of the minimum voltage threshold, and a corresponding increase of the total current in the low-voltage regime. At higher voltages, our findings indicate a significant increase of transport only for P-doped Si-QDs, while the electrical response of B-doped ones does not stray from the undoped case. These findings are of support for the employment of doped Si-QDs in a wide range of applications, such as Si-based photonics or photovoltaic solar cells. PMID- 26144525 TI - Evidence of pressure induced intermolecular proton transfer via mutarotation: the case of supercooled d-fructose. AB - This paper describes a systematic investigation on the role of pressure in mutarotation kinetics of supercooled d-fructose using dielectric spectroscopy. The structural relaxation time acts as a suitable dynamical observable to monitor the mutarotation process that enables the construction of the kinetic curves. The reaction kinetic shapes have been analyzed using the Avrami model. At low temperature, sigmoidal kinetic curves are noted, which correspond to the high concentration of furanosidic forms. The magnitude of activation energy of the process significantly decreases with increasing pressure and is comparable to the solvated systems at 100 MPa. A potential connection between cooperative motion and the origin of intermolecular proton transfer via mutarotation at elevated pressure is also discussed. These experimental observations have fundamental significance on theoretical explanation of the mechanism involving mutarotation in sugars. PMID- 26144526 TI - Curing kinetics and morphology of a nanovesicular epoxy/stearyl-block poly(ethylene oxide) surfactant system. AB - Brittle epoxy based thermosets can be made tougher by introducing structural inhomogeneities at the micro- or nanoscale. In that respect, nano vesicles and worm-like micelles from self-assembling blockcopolymers have been shown to be very effective. This paper describes the curing kinetics and morphology of an epoxy composed of diglycidyl ether of bisphenol A (DGEBA) and 4,4' methylenedianiline (MDA), modified by 20% of the surfactant stearyl-block poly(ethylene oxide). Time resolved, synchrotron small-angle X-ray scattering demonstrates that at any time during the epoxy curing process, the surfactant predominantly adopts a bilayer vesicular nano-morphology. Transmission electron microscopy on fully cured systems reveals the coexistence of spherical and worm like micelles. Differential scanning calorimetry experiments prove that the presence of surfactant reduces the epoxy curing rate but that ultimately full curing is accomplished. The material glass transition temperature falls below that of the pure resin due to plasticization. It is suggested that favorable secondary interactions between the PEO segments and the epoxy resin are responsible for the observed phenomena. PMID- 26144528 TI - Anti-Markovnikov hydroimination of terminal alkynes in gold-catalyzed pyridine construction from ammonia. AB - Gold-catalyzed hydroimination of terminal alkynes, giving rise to anti Markovnikov adducts concomitant with unstable Markovnikov adducts is described. The elementary step can be applied for the construction of pyridine derivatives from ammonia and alkynes. PMID- 26144527 TI - Proteogenomics Dashboard for the Human Proteome Project. AB - dasHPPboard is a novel proteomics-based dashboard that collects and reports the experiments produced by the Spanish Human Proteome Project consortium (SpHPP) and aims to help HPP to map the entire human proteome. We have followed the strategy of analog genomics projects like the Encyclopedia of DNA Elements (ENCODE), which provides a vast amount of data on human cell lines experiments. The dashboard includes results of shotgun and selected reaction monitoring proteomics experiments, post-translational modifications information, as well as proteogenomics studies. We have also processed the transcriptomics data from the ENCODE and Human Body Map (HBM) projects for the identification of specific gene expression patterns in different cell lines and tissues, taking special interest in those genes having little proteomic evidence available (missing proteins). Peptide databases have been built using single nucleotide variants and novel junctions derived from RNA-Seq data that can be used in search engines for sample specific protein identifications on the same cell lines or tissues. The dasHPPboard has been designed as a tool that can be used to share and visualize a combination of proteomic and transcriptomic data, providing at the same time easy access to resources for proteogenomics analyses. The dasHPPboard can be freely accessed at: http://sphppdashboard.cnb.csic.es. PMID- 26144529 TI - Calibration independent generalized cavity method for microwave characterization of powdered materials. AB - A generalized cavity method relaxing the major assumptions of conventional cavity perturbation technique is presented for characterization of the powdered sample in the microwave frequency range. The unified method, which is based on the inverse optimization technique, eliminates the complexity of measurement caused due to the existence of sample holder and produces an accurate result. In this paper, an attractive numerical calibration approach is proposed in lieu of the practical calibration technique which usually requires either a set of standards or a number of reference samples. The sample holder especially made of borosilicate glass is designed to contain the powdered samples, and the X-band rectangular cavity is fabricated. For verification of the proposed technique, the pulverized alumina and polyethylene oxide with various packing fractions are measured using the fabricated cavity and the vector network analyzer. The dielectric constant of these samples is extracted using the proposed unified approach which is found to be in good agreement with the theoretical data obtained by Landau-Lifshitz and Looyenga model. The accuracy of the proposed generalized cavity method for powdered samples is found to be better than the conventional resonator methods available in the literature. PMID- 26144530 TI - Tuning of structure and enhancement of upconversion luminescence in NaLuF4:Yb(3+),Ho(3+) crystals. AB - A series of NaLuF4:Yb(3+),Ho(3+) nano/micro-crystals with different crystal structures were synthesized via a hydrothermal method using citric acid as a chelating agent. The influences of NaF content, Li(+) doping, reaction temperature and reaction time on the crystal structure and shape of the as synthesized NaLuF4 crystals were systematically investigated. To the best of our knowledge, it is the first time to report Li(+) doped alpha-NaLuF4:Yb(3+),Ho(3+) nanocrystals and the phase transformation by introducing Li(+) in NaLuF4 crystals. As for Li(+) doped alpha-NaLuF4, UC luminescence intensities of green emission (538 nm) and red emission (644 nm) in alpha-NaLuF4:Yb(3+),Ho(3+) nanocrystals with 20 mol% Li(+) doping are enhanced by 20 and 3.5 times compared to their Li(+)-free counterpart. As for Li(+) doped alpha/beta-mixed NaLuF4, with the increase of Li(+) content, the phase transforms from the alpha/beta-mixed phase to hexagonal then to cubic. UC emissions of 538 nm and 644 nm in NaLuF4:Yb(3+),Ho(3+) crystals doped with 5 mol% Li(+) are enhanced by 26.5 and 23 times, respectively. Besides, it is found that with the higher temperature and prolonged time, the morphology of NaLuF4 changes from nanoparticles to microtubes, resulting in the dramatic increase of UC emission intensity. The effects of Li(+) doping, reaction temperature and reaction time on the enhancement of UC emission intensity are discussed in detail. This study provides an effective and facile approach to obtain nano/micro-crystals with controllable structures and excellent optical properties. PMID- 26144531 TI - Chiral porous metal-organic frameworks containing MU-oxo-bis[Ti(salan)] units for asymmetric cyanation of aldehydes. AB - Two chiral porous Ti(salan)-based metal-organic frameworks are constructed and are shown to be efficient and recyclable heterogeneous catalysts for asymmetric cyanation reaction of aldehydes, displaying significantly higher enantioselectivity than their homogeneous counterpart. PMID- 26144532 TI - Simultaneous sensing of UV light and strain with a single-layer network structure of self-assembled ZnO nanorods. AB - A route for the self-assembly of a single-layer network structure (SLNS) of nanorods (NRs) was introduced and its various material properties were investigated. Considering the properties of the ZnO NR SLNS, we suggested an algorithm and a device for simultaneously sensing UV light and strain to determine the UV intensity and strain in a UV-illuminated bent position. PMID- 26144533 TI - Which charge definition for describing the crystal polarizing field and the chi((1)) and chi((2)) of organic crystals? AB - The impact of atomic charge definition for describing the crystal polarizing electric field has been assessed in view of predicting the linear and nonlinear optical susceptibilities of molecular crystals. In this approach, the chromophores are embedded in the electric field of its own point charges, which are evaluated through a self-consistent procedure including charge scaling to account for the screening of the dielectric. Once the crystal field is determined, dressed molecular polarizabilities and hyperpolarizabilities are calculated and used as input of an electrostatic interaction scheme to evaluate the crystal linear and nonlinear optical responses. It is observed that many charge definitions (i) based on partitioning the electron density (QTAIM), (ii) obtained by analyzing the quantum-chemical wavefunction (Mulliken, MBS, and NBO), and (iii) derived by fitting to the electrostatic potential (MK, CHelpG, and HLYGAt) give very consistent results and are equally valid whereas Hirshfeld partitioning and CM5 charge parametrizations underestimate the refractive indices and second-order nonlinear optical susceptibilities. An alternative approach omitting charge scaling is demonstrated to overestimate the different crystal optical properties. On the other hand, the molecule embedding approach provides results in close agreement with those calculated with a charge field obtained from periodic boundary condition calculations. PMID- 26144534 TI - Acidity-Mediated, Electrostatic Tuning of Asymmetrically Charged Peptides Interactions with Protein Nanopores. AB - Despite success in probing chemical reactions and dynamics of macromolecules on submillisecond time and nanometer length scales, a major impasse faced by nanopore technology is the need to cheaply and controllably modulate macromolecule capture and trafficking across the nanopore. We demonstrate herein that tunable charge separation engineered at the both ends of a macromolecule very efficiently modulates the dynamics of macromolecules capture and traffic through a nanometer-size pore. In the proof-of-principle approach, we employed a 36 amino acids long peptide containing at the N- and C-termini uniform patches of glutamic acids and arginines, flanking a central segment of asparagines, and we studied its capture by the alpha-hemolysin (alpha-HL) and the mean residence time inside the pore in the presence of a pH gradient across the protein. We propose a solution to effectively control the dynamics of peptide interaction with the nanopore, with both association and dissociation reaction rates of peptide-alpha HL interactions spanning orders of magnitude depending upon solution acidity on the peptide addition side and the transmembrane electric potential, while preserving the amplitude of the blockade current signature. PMID- 26144535 TI - HPV and the Ethics of CDC's Vaccination Requirements for Immigrants. AB - The United States may justifiably exclude unvaccinated aliens, perhaps even under the assumption of Open Borders, according to which people should generally be permitted to settle in countries of their choosing. Furthermore, there are good reasons to endorse the Centers for Disease Control and Prevention's (CDC's) current vaccination-related exclusion criteria, which were last revised in 2009. I frame my discussion around CDC's 2008 decision to permit immigrant girls and women to be excluded if they were not vaccinated against human papillomavirus (HPV)-a decision that was quickly reversed and that led to the 2009 revisions to CDC's vaccination-related immigrant exclusion criteria. PMID- 26144536 TI - Immigration Justice and the Grounds for Mandatory Vaccinations. AB - For over a century, a foreign national seeking permission to immigrate to the U.S. could have her application for immigration denied on the ground that she suffers from a serious contagious disease. For just under two decades, a foreign national seeking permission to immigrate could also have her application denied on the ground that she has not been vaccinated against each of a list of vaccination-preventable diseases. Two recently developed moral justifications for the use of such "vaccination-related exclusion criteria" have focused on (a) the right and need of a society to prevent the spread of disease to others and (b) the public good of developing and protecting herd immunity. Herein I accept these two general justifications-especially as they are developed by Mark Navin-and explore their limits. In particular, with a focus on the recently developed vaccine against several strains of HPV, as well the short-lived requirement by the CDC that it, too, be required of prospective immigrants, I argue that neither of the two main justifications for the use of vaccination-related exclusion criteria support their use for diseases such as HPV (or even HIV), the transmission of which, unlike airborne diseases such as measles, pertussis and polio, is subject to a considerable degree of individual control. PMID- 26144537 TI - Gamete Donor Consent and Human Embryonic Stem Cell Research. AB - There is a lack of consensus on whether the derivation and use of human embryonic stem cells (hESCs) from embryos remaining after infertility treatment morally require the informed consent of third-party gamete donors who contributed to the creation of the embryos. The principal guidelines for oversight and funding of hESC research in the United States make minimal or no demands for consent from gamete donors. In this article, I consider the arguments supporting and opposing gamete donor consent for hESC research and embryo research more broadly. I argue that it is not morally permissible to use leftover embryos in research without the informed consent of gamete donors, and that we should place restrictions on the use of existing hESC lines that may have been derived without informed consent. While the standard argument for this position relies on an appeal to gamete donors' interest in controlling what happens with their genetic material, I identify shortcomings with the standard approach and seek instead to locate the deeper moral foundations for gamete donor consent in rights to bodily integrity. PMID- 26144538 TI - Robot Lies in Health Care: When Is Deception Morally Permissible? AB - Autonomous robots are increasingly interacting with users who have limited knowledge of robotics and are likely to have an erroneous mental model of the robot's workings, capabilities, and internal structure. The robot's real capabilities may diverge from this mental model to the extent that one might accuse the robot's manufacturer of deceiving the user, especially in cases where the user naturally tends to ascribe exaggerated capabilities to the machine (e.g. conversational systems in elder-care contexts, or toy robots in child care). This poses the question, whether misleading or even actively deceiving the user of an autonomous artifact about the capabilities of the machine is morally bad and why. By analyzing trust, autonomy, and the erosion of trust in communicative acts as consequences of deceptive robot behavior, we formulate four criteria that must be fulfilled in order for robot deception to be morally permissible, and in some cases even morally indicated. PMID- 26144539 TI - Filling in the Gaps: Priming and the Ethics of Pharmaceutical Advertising. AB - A prime is a cue that makes associated concepts, behaviors, and goals more psychologically accessible to people, influencing their responses in subsequent related environments. I build a case that Direct to Consumer Advertising of Prescription Pharmaceuticals (DTCA) operates as a prime that causes some viewers to prefer and pursue the advertised drug. Drawing on literature from social psychology I show that people subject to priming are mostly unaware of its influence and liable to misattribute the reasons for their primed actions. Misattribution typically includes heightened appraisals of the value of a primed goal. Consistent with this account, I argue that viewers primed by DTCA hold favorable, yet false beliefs about the safety and efficacy of the advertised drug. I further argue that, because those drug properties are material to viewers with the relevant illness, priming in DTCA can undermine the autonomy of their medicine choices. The threat to autonomy posed by priming in DTCA suggests it warrants attention from both regulators and the wider research community. It also adds further reason to be sceptical about the permissibility of this form of advertising. PMID- 26144540 TI - Editorial Note. PMID- 26144542 TI - Design of Modified Amine Transfer Reagents Allows the Synthesis of alpha-Chiral Secondary Amines via CuH-Catalyzed Hydroamination. AB - The CuH-catalyzed hydroamination of alkenes and alkynes using a silane and an amine transfer reagent represents a simple strategy to access chiral amine products. We have recently reported methods to prepare chiral amines with high efficiency and stereoselectivity using this approach. However, the current technology is limited to the synthesis of trialkylamines from dialkylamine transfer reagents (R2NOBz). When monoalkylamine transfer reagents [RN(H)OBz] were used for the synthesis of chiral secondary amines, competitive, nonproductive consumption of these reagents by the CuH species resulted in poor yields. In this paper, we report the design of a modified type of amine transfer reagent that addresses this limitation. This effort has enabled us to develop a CuH-catalyzed synthesis of chiral secondary amines using a variety of amine coupling partners, including those derived from amino acid esters, carbohydrates, and steroids. Mechanistic investigations indicated that the modified amine transfer reagents are less susceptible to direct reaction with CuH. PMID- 26144543 TI - The safety and long-term efficacy of zonisamide as adjunctive therapy for focal epilepsy. AB - Epilepsy is a chronic disease which affects 1% of the population worldwide. As treatment is required for many years or decades, the long-term efficacy and tolerability of antiepileptic drugs are particularly important. Zonisamide (ZNS) is a second-generation antiepileptic drug with a unique structure and multiple mechanisms of action. Here, recently published long-term outcomes of patient cohorts with focal epilepsy undergoing ZNS treatment are discussed. Whereas ZNS monotherapy maintains similar seizure control efficacy to carbamazepine after 2 years of treatment, seizure-free rates are low in pharmacoresistant patients undergoing late adjunctive therapy. In preselected patient populations derived from double-blind studies, long-term seizure reduction and responder rates support sustained ZNS efficacy, good adherence and long-term retention. Adverse effects include somnolence and weight decrease, but data suggest that long-term treatment with ZNS is safe with only rare newly occurring adverse effects, and good long-term tolerability also regarding mood, behavior, cognition and bone maturation. PMID- 26144544 TI - Mental healthcare in older adults with schizophrenia: results from 118 French public psychiatric departments. PMID- 26144545 TI - Procedural learning: A developmental study of motor sequence learning and probabilistic classification learning in school-aged children. AB - In this study, we investigated motor and cognitive procedural learning in typically developing children aged 8-12 years with a serial reaction time (SRT) task and a probabilistic classification learning (PCL) task. The aims were to replicate and extend the results of previous SRT studies, to investigate PCL in school-aged children, to explore the contribution of declarative knowledge to SRT and PCL performance, to explore the strategies used by children in the PCL task via a mathematical model, and to see whether performances obtained in motor and cognitive tasks correlated. The results showed similar learning effects in the three age groups in the SRT and in the first half of the PCL tasks. Participants did not develop explicit knowledge in the SRT task whereas declarative knowledge of the cue-outcome associations correlated with the performances in the second half of the PCL task, suggesting a participation of explicit knowledge after some time of exposure in PCL. An increasing proportion of the optimal strategy use with increasing age was observed in the PCL task. Finally, no correlation appeared between cognitive and motor performance. In conclusion, we extended the hypothesis of age invariance from motor to cognitive procedural learning, which had not been done previously. The ability to adopt more efficient learning strategies with age may rely on the maturation of the fronto-striatal loops. The lack of correlation between performance in the SRT task and the first part of the PCL task suggests dissociable developmental trajectories within the procedural memory system. PMID- 26144546 TI - Regulating the therapeutic translation of regenerative medicine. AB - Regenerative medicine and stem cell research are exciting new fields. But as the fields progress toward clinical therapies, controversies emerge. Hype surrounding stem cell research has caused an increase in their use in interventions that are not clinically proven. Furthermore, the regulatory agencies have a lot of difficulty dealing with cell therapies, which are distinctly different from drugs and medical devices they more commonly approve. To move the field forward, advocates, regulators and scientists need to come together to find new options for stem cell research oversight that protects both the patients and the research field. PMID- 26144548 TI - Development and evaluation of an audiology app for iPhone/iPad mobile devices. AB - CONCLUSION: The application described in this study appears to be accurate and valid, thus allowing calculation of a hearing handicap and assessment of the pure tone air conduction threshold with iPhone/iPad devices. OBJECTIVE: To develop and evaluate a newly developed professional, computer-based hearing handicap calculator and a manual hearing sensitivity assessment test for the iPhone and iPad (AudCal). METHODS: Multi-center prospective non-randomized validation study. One hundred and ten consecutive adult participants underwent two hearing evaluations, a standard audiometry and a pure-tone air conduction test using AudCal with an iOS device. The hearing handicap calculation accuracy was evaluated comparing AudCal vs a web-based calculator. RESULTS: Hearing loss was found in 83 and 84 out of 220 standard audiometries and AudCal hearing tests (Cohen's Kappa = 0.89). The mean difference between AudCal and standard audiogram thresholds was -0.21 +/- 6.38 dB HL. Excellent reliability and concordance between standard audiometry and the application's hearing loss assessment test were obtained (Cronbach's alpha = 0.96; intra-class correlation coefficient = 0.93). AudCal vs a web-based calculator were perfectly correlated (Pearson's r = 1). PMID- 26144549 TI - A Facile Route for Patterned Growth of Metal-Insulator Carbon Lateral Junction through One-Pot Synthesis. AB - Precise graphene patterning is of critical importance for tailor-made and sophisticated two-dimensional nanoelectronic and optical devices. However, graphene-based heterostructures have been grown by delicate multistep chemical vapor deposition methods, limiting preparation of versatile heterostructures. Here, we report one-pot synthesis of graphene/amorphous carbon (a-C) heterostructures from a solid source of polystyrene via selective photo-cross linking process. Graphene is successfully grown from neat polystyrene regions, while patterned cross-linked polystyrene regions turn into a-C because of a large difference in their thermal stability. Since the electrical resistance of a-C is at least 2 orders of magnitude higher than that for graphene, the charge transport in graphene/a-C heterostructure occurs through the graphene region. Measurement of the quantum Hall effect in graphene/a-C lateral heterostructures clearly confirms the reliable quality of graphene and well-defined graphene/a-C interface. The direct synthesis of patterned graphene from polymer pattern could be further exploited to prepare versatile heterostructures. PMID- 26144550 TI - Core-shell Au@Pd nanoparticles with enhanced catalytic activity for oxygen reduction reaction via core-shell Au@Ag/Pd constructions. AB - Core-shell nanoparticles often exhibit improved catalytic properties due to the lattice strain created in these core-shell particles. Herein, we demonstrate the synthesis of core-shell Au@Pd nanoparticles from their core-shell Au@Ag/Pd parents. This strategy begins with the preparation of core-shell Au@Ag nanoparticles in an organic solvent. Then, the pure Ag shells are converted into the shells made of Ag/Pd alloy by galvanic replacement reaction between the Ag shells and Pd(2+) precursors. Subsequently, the Ag component is removed from the alloy shell using saturated NaCl solution to form core-shell Au@Pd nanoparticles with an Au core and a Pd shell. In comparison with the core-shell Au@Pd nanoparticles upon directly depositing Pd shell on the Au seeds and commercial Pd/C catalysts, the core-shell Au@Pd nanoparticles via their core-shell Au@Ag/Pd templates display superior activity and durability in catalyzing oxygen reduction reaction, mainly due to the larger lattice tensile effect in Pd shell induced by the Au core and Ag removal. PMID- 26144551 TI - Waste-Activated Sludge Fermentation for Polyacrylamide Biodegradation Improved by Anaerobic Hydrolysis and Key Microorganisms Involved in Biological Polyacrylamide Removal. AB - During the anaerobic digestion of dewatered sludge, polyacrylamide (PAM), a chemical conditioner, can usually be consumed as a carbon and nitrogen source along with other organic matter (e.g., proteins and carbohydrates in the sludge). However, a significant accumulation of acrylamide monomers (AMs) was observed during the PAM biodegradation process. To improve the anaerobic hydrolysis of PAM, especially the amide hydrolysis process, and to avoid the generation of the intermediate product AM, a new strategy is reported herein that uses an initial pH of 9, 200 mg COD/L of PAM and a fermentation time of 17 d. First, response surface methodology (RSM) was applied to optimize PAM removal in the anaerobic digestion of the sludge. The biological hydrolysis of PAM reached 86.64% under the optimal conditions obtained from the RSM. Then, the mechanisms for the optimized parameters that significantly improved the biological hydrolysis of PAM were investigated by the synergistic effect of the main organic compounds in the sludge, the floc size distribution, and the enzymatic activities. Finally, semi continuous-flow experiments for a microbial community study were investigated based on the determination of key microorganisms involved in the biological hydrolysis of PAM. PMID- 26144552 TI - Formation and manipulation of cell spheroids using a density adjusted PEG/DEX aqueous two phase system. AB - Various spheroid formation techniques have been widely developed for efficient and reliable 3-D cell culture research. Although those efforts improved many aspects of spheroid generation, the procedures became complex and also required unusual laboratory equipment. Many recent techniques still involve laborious pipetting steps for spheroid manipulation such as collection, distribution and reseeding. In this report, we used a density-controlled polyethylene glycol and dextran aqueous two phase system to generate spheroids that are both consistent in size and precisely size-controllable. Moreover, by adding a few drops of fresh medium to the wells the contain spheroids, they can be simply settled and attached to the culture surface due to reduced densities of the phases. This unique attribute of the technique significantly reduces the numerous pipetting steps of spheroid manipulation to a single pipetting; therefore, the errors from those steps are eliminated and the reliability and efficiency of a research can be maximized. PMID- 26144553 TI - The GATA transcription factor GtaC regulates early developmental gene expression dynamics in Dictyostelium. AB - In many systems, including the social amoeba Dictyostelium discoideum, development is often marked by dynamic morphological and transcriptional changes orchestrated by key transcription factors. However, efforts to examine sequential genome-wide changes of gene regulation in developmental processes have been fairly limited. Here we report the developmental regulatory dynamics of GtaC, a GATA-type zinc-finger transcription factor, through the analyses of serial ChIP- and RNA-sequencing data. GtaC is essential for developmental progression, decoding extracellular cAMP pulses during early development and may play a role in mediating cell-type differentiation at later stages. We find that GtaC exhibits temporally distinctive DNA-binding patterns concordant with each developmental stage. We identify direct GtaC targets and observe cotemporaneous GtaC-binding and developmental expression regulation. Our results suggest that GtaC regulates multiple physiological processes as Dictyostelium transitions from a group of unicellular amoebae to an integrated multicellular organism. PMID- 26144555 TI - Investigating integument alterations in cubicle housed dairy cows: which types and locations can be combined? AB - In this study, a data set of 2922 lactating dairy cows in a sample of 64 conventional and organic dairy farms with Holstein Friesian cows in Germany and 31 conventional dairy farms with the dual purpose breed Fleckvieh in Austria was used to screen for correlations between the occurrences of different integument alterations. All cows were housed in cubicle systems. Alterations were classified as hairless areas (H), scabs or wounds (W) or swellings (S) and assessed at 15 locations of the cows' body. Highest median farm prevalences were found at the joints of the legs, which are already commonly included in studies on integumentary alterations: median farm prevalence was 83% for S and 48% for H at the carpal joints, followed by H (38%) and S (20%) at the lateral tarsal joints and H at the lateral calcanei (20%). Additional body parts with notable median prevalences for H were the hip bones (13%), pin bones (12%) and sacrum (11%). Three cluster models, with 2, 5 and 14 clusters, were built by hierarchical clustering of prevalences of the 30 most relevant alteration location combinations. Clustering revealed that location overruled type of lesion in most cases. Occasionally, clusters represented body segments significantly distant from each other, for example the carpal joints and lateral and dorsal calcanei. However, some neighbouring areas such as the medial and lateral hock area should be analysed separately from each other for causal analysis as they formed distinct clusters. PMID- 26144556 TI - Cumulative deficit model of geriatric assessment to predict the postoperative outcomes of older patients with solid abdominal cancer. AB - OBJECTIVE: The geriatric assessment (GA) has proven to be of great value for clinicians treating older patients. However, a clear consensus on the optimal set of GA instruments is lacking, particularly for surgical patients. Therefore, the aim of this prospective study was to compare the prevalence of frailty, depending on the number of incorporated GA domains, and to evaluate its accuracy in predicting postoperative outcome. MATERIALS AND METHODS: Seventy-five patients aged 65 years and older, qualified for abdominal surgery due to solid cancer, were enrolled. The GA included a wide variety of validated tools that evaluate functional, mobility, nutritional, co-morbidity, polypharmacy, and psychosocial domains. RESULTS: Depending on the number of incorporated GA domains the frequency of frailty was 23-97%. The cumulative score rather than individual components of the GA, turned out to be an independent risk factor of 30-day postoperative morbidity. In predicting 30-day "any" and "major" morbidities, the area under the curve was 0.67-0.72 and 0.70-0.82 (model including the severity of the surgery) vs. 0.57-0.66 and 0.50-0.65 (model not including the severity of the surgery), respectively. CONCLUSION: The number of incorporated GA domains has a great influence on the prevalence of frailty and on adequate surgical risk assessment. The summary deficit score based on Pre-operative Assessment of Cancer in the Elderly (PACE) or the GA consisting of functional, mobility, cognitive, depression, nutritional, co-morbidity, polypharmacy, and social support assessment domains can predict 30-day postoperative morbidity. However, only models with addition of the severity of surgery show moderate to good predictive value. PMID- 26144554 TI - Aneuploidy generates proteotoxic stress and DNA damage concurrently with p53 mediated post-mitotic apoptosis in SAC-impaired cells. AB - The molecular mechanism responsible that determines cell fate after mitotic slippage is unclear. Here we investigate the post-mitotic effects of different mitotic aberrations--misaligned chromosomes produced by CENP-E inhibition and monopolar spindles resulting from Eg5 inhibition. Eg5 inhibition in cells with an impaired spindle assembly checkpoint (SAC) induces polyploidy through cytokinesis failure without a strong anti-proliferative effect. In contrast, CENP-E inhibition causes p53-mediated post-mitotic apoptosis triggered by chromosome missegregation. Pharmacological studies reveal that aneuploidy caused by the CENP E inhibitor, Compound-A, in SAC-attenuated cells causes substantial proteotoxic stress and DNA damage. Polyploidy caused by the Eg5 inhibitor does not produce this effect. Furthermore, p53-mediated post-mitotic apoptosis is accompanied by aneuploidy-associated DNA damage response and unfolded protein response activation. Because Compound-A causes p53 accumulation and antitumour activity in an SAC-impaired xenograft model, CENP-E inhibitors could be potential anticancer drugs effective against SAC-impaired tumours. PMID- 26144557 TI - How children aged seven to twelve organize the opening sequence in a map task. AB - Using the methods of conversation analysis, the opening sequences of a map task in the interactions of sixteen children aged seven to twelve were analyzed. The analytical concerns driving the study were who started, how they started, and how children dealt with differential access to information and the identification of phases within the opening. It was found that all participants oriented to the instruction-giver as the one to start, even when the information-follower commenced the task. With respect to how to start, the older children produced a question and answer sequence or a try-mark to establish a common starting point. Five of the eight younger children inferred a common starting point on the map. Three recurring phases were identified: readiness to begin established through a discourse marker, location of the starting point, and actual instruction. The findings are discussed with reference to the importance of interaction in referential spatial tasks. PMID- 26144558 TI - Landscape irrigation management for maintaining an aquifer and economic returns. AB - Expanding irrigated agriculture and dryer climatic conditions has led to large scale withdrawals of groundwater and the decline in shallow aquifers. Policy makers must wrestle with the challenge of maintaining economic growth while conserving the groundwater resource. A spatially explicit landscape level model analyzes consequences of optimally chosen crop mix patterns on an aquifer and economic returns. The model of the groundwater use incorporates irrigation needs of the crops grown, initial aquifer thickness, hydro-conductivity of the aquifer, and distance to surrounding grid cells. The economic model incorporates the site specific yield, crop mix, and irrigation practice investments to predict economic returns. A tradeoff occurs between the volume of the aquifer and economic returns due to groundwater withdrawal for irrigation, but the farm's ability to grow profitable lower irrigation crops dampens the intensity of this tradeoff. Allowing for multiple unconventional irrigation practices that are yield increasing and water conserving significantly increases the economic returns of a given crop mix while maintaining the aquifer. PMID- 26144559 TI - Equilibrium strategy-based optimization method for the coal-water conflict: A perspective from China. AB - Environmental water problems have become increasingly severe, with the coal-water conflict becoming one of the most difficult issues in large scale coal mining regions. In this paper, a bi-level optimization model based on the Stackelberg Nash equilibrium strategy with fuzzy coefficients is developed to deal with environmental water problems in large scale coal fields, in which both the groundwater quality and quantity are considered. Using the proposed model, and fully considering the relationship between the authority and the collieries and also the equilibrium between economic development and environmental protection, an environmental protection based mining quotas competition mechanism is established. To deal with the inherent uncertainties, the model is defuzzified using a possibility measure, and a solution approach based on the Karush-Kuhn Tucker condition is designed to search for the solutions. A case study is presented to demonstrate the practicality and efficiency of the model, and different constraint violation risk levels and related results are also obtained. The results showed that under the environmental protection based mining quotas competition mechanism, collieries attempt to conduct environmentally friendly exploitation to seek greater mining quotas. This demonstrates the practicality and efficiency in the proposed model of reducing the coal-water conflict. Finally, a comprehensive discussion is provided and some propositions is given as a foundation for the proposed management recommendations. PMID- 26144560 TI - System tradeoffs in siting a solar photovoltaic material recovery infrastructure. AB - The consumption and disposal of rare and hazardous metals contained in electronics and emerging technologies such as photovoltaics increases the material complexity of the municipal waste stream. Developing effective waste policies and material recovery systems is required to inhibit landfilling of valuable and finite resources. This work developed a siting and waste infrastructure configuration model to inform the management and recovery of end of-life photovoltaics. This model solves the siting and waste location-allocation problem for a New York State case study by combining multi-criteria decision methods with spatial tools, however this methodology is generalizable to any geographic area. For the case study, the results indicate that PV installations are spatially statistically significant (i.e., clustered). At least 9 sites, which are co-located with landfills and current MRFs, were 'highly' suitable for siting according to our criteria. After combining criteria in an average weighted sum, 86% of the study area was deemed unsuitable for siting while less than 5% is characterized as highly suitable. This method implicitly prioritized social and environmental concerns and therefore, these concerns accounted for the majority of siting decisions. As we increased the priority of economic criteria, the likelihood of siting near ecologically sensitive areas such as coastline or socially vulnerable areas such as urban centers increased. The sensitivity of infrastructure configurations to land use and waste policy are analyzed. The location allocation model results suggest current tip fees are insufficient to avoid landfilling of photovoltaics. Scenarios where tip fees were increased showed model results where facilities decide to adopt limited recycling technologies that bypass compositionally complex materials; a result with strong implications for global PV installations as well as other waste streams. We suggest a multi-pronged approach that lowers technology cost, imposes a minimum collection rate, and implements higher tip fees would encourage exhaustive material recovery for solar photovoltaic modules at end-of-life, beyond New York State. These results have important implications for policy makers and waste managers especially in locations where there is rapid adoption of renewable energy technologies. PMID- 26144561 TI - Residential surface soil guidance applied worldwide to the pesticides added to the Stockholm Convention in 2009 and 2011. AB - Due to the widespread use of agricultural and residential pesticides, the potential for pesticide soil contamination is a worldwide concern. In response, regulatory jurisdictions in at least 54 nations have promulgated guidance values to specify the maximum allowable concentration of pesticides in soils. Guidance values may be found for more than 700 pesticides. A previous analysis examined the values applied to the original "dirty dozen" persistent organic pollutant (POP) pesticides that were addressed in the 2001 Stockholm Convention (Aldrin, Chlordane, DDT, Dieldrin, Endrin, Heptachlor, Mirex, and Toxaphene). Results are presented here for the "new POP" pesticides that were added to the Stockholm Convention in 2009 and 2011 (isomers of Hexachlorocyclohexane, Chlordecone, and isomers of Endosulfan). The guidance value extremes used worldwide for these pesticides vary by as much as 8.5 orders of magnitude and the randomness in their distributions resembles that of lognormal random variables. However, there are nonrandom value clusters in some distributions that may identify values around which consensuses are forming. The current value distributions imply that a wide range of human health risks are being accepted. Hopefully, the results presented will help regulatory jurisdictions and the regulated communities identify values that should be revised to be adequately protective of human health. PMID- 26144562 TI - Development of a loop-mediated isothermal amplification method for the rapid detection of the dioxin-degrading bacterium Ochrobactrum anthropi in soil. AB - In this study, loop-mediated isothermal amplification (LAMP) and real-time LAMP assays were developed to detect the dioxin-degrading bacterium Ochrobactrum anthropi strain BD-1 in soil. Four primers were designed to use ITS gene amplification for the strain O. anthropi BD-1. The real-time LAMP assay was found to accomplish the reaction by 1 pg of genomic DNA load when used for nucleic acid amplification. This assay was then applied to detect O. anthropi BD-1 in eight soil samples collected from a dioxin-contaminated site. The results demonstrated that these newly developed LAMP and real-time LAMP assays will not only be useful and efficient tools for detecting the target gene, but also be used as molecular tools for monitoring the growth of dioxin-degrading O. anthropi in the soil. This is the first report to demonstrate the use of LAMP assays to monitor the presence of O. anthropi in dioxin-contaminated soil. The application of this method should improve the biomonitoring of dioxin contamination. PMID- 26144563 TI - Evaluating adaptive co-management as conservation conflict resolution: Learning from seals and salmon. AB - By linking iterative learning and knowledge generation with power-sharing, adaptive co-management (ACM) provides a potential solution to resolving complex social-ecological problems. In this paper we evaluate ACM as a mechanism for resolving conservation conflict using a case study in Scotland, where seal and salmon fishery stakeholders have opposing and entrenched objectives. ACM emerged in 2002, successfully resolving this long-standing conflict. Applying evaluation approaches from the literature, in 2011 we interviewed stakeholders to characterise the evolution of ACM, and factors associated with its success over 10 years. In common with other ACM cases, triggers for the process were shifts in slow variables controlling the system (seal and salmon abundance, public perceptions of seal shooting), and exogenous shocks (changes in legal mandates, a seal disease outbreak). Also typical of ACM, three phases of evolution were evident: emerging local leadership preparing the system for change, a policy window of opportunity, and stakeholder partnerships building the resilience of the system. Parameters maintaining ACM were legal mechanisms and structures, legal power held by government, and the willingness of all stakeholders to reach a compromise and experiment with an alternative governance approach. Results highlighted the critical role of government power and support in resolving conservation conflict, which may constrain the extent of local stakeholder-driven ACM. The evaluation also demonstrated how, following perceived success, the trajectory of ACM has shifted to a 'stakeholder apathy' phase, with declining leadership, knowledge exchange, stakeholder engagement, and system resilience. We discuss remedial actions required to revive the process, and the importance of long term government resourcing and alternative financing schemes for successful conflict resolution. Based on the results we present a generic indicator framework and participatory method for the longitudinal evaluation of ACM applied to conservation conflict resolution. PMID- 26144564 TI - Prioritization methodology for the monitoring of active pharmaceutical ingredients in hospital effluents. AB - The important number of active pharmaceutical ingredients (API) available on the market along with their potential adverse effects in the aquatic ecosystems, lead to the development of prioritization methods, which allow choosing priority molecules to monitor based on a set of selected criteria. Due to the large volumes of API used in hospitals, an increasing attention has been recently paid to their effluents as a source of environmental pollution. Based on the consumption data of a Swiss university hospital, about hundred of API has been prioritized following an OPBT approach (Occurrence, Persistence, Bioaccumulation and Toxicity). In addition, an Environmental Risk Assessment (ERA) allowed prioritizing API based on predicted concentrations and environmental toxicity data found in the literature for 71 compounds. Both prioritization approaches were compared. OPBT prioritization results highlight the high concern of some non steroidal anti-inflammatory drugs and antiviral drugs, whereas antibiotics are revealed by ERA as potentially problematic to the aquatic ecosystems. Nevertheless, according to the predicted risk quotient, only the hospital fraction of ciprofloxacin represents a risk to the aquatic organisms. Some compounds were highlighted as high-priority with both methods: ibuprofen, trimethoprim, sulfamethoxazole, ritonavir, gabapentin, amoxicillin, ciprofloxacin, raltegravir, propofol, etc. Analyzing consumption data and building prioritization lists helped choosing about 15 API to be monitored in hospital wastewaters. The API ranking approach adopted in this study can be easily transposed to any other hospitals, which have the will to look at the contamination of their effluents. PMID- 26144565 TI - Trapdoor Pneumopericardium. PMID- 26144566 TI - Microsurgical resection of Spetzler-Martin grades 1 and 2 unruptured brain arteriovenous malformations results in lower long-term morbidity and loss of quality-adjusted life-years (QALY) than conservative management--results of a single group series. AB - BACKGROUND: The therapeutic benefits of microsurgery for unruptured brain AVM remain unclear. METHODS: A series of 97 microsurgically resected unruptured brain AVM was analyzed in terms of postoperative morbidity and lifetime loss of quality adjusted life-years (QALY). For comparison, the natural risk of becoming disabled was modeled on the basis of published data. RESULTS: Discharge morbidity was recorded in 11 of the 69 of Spetzler-Martin (SM) grade 1 and 2 AVMs (16 %), eight of 22 (36 %) grade 3, and four of six grade 4 (67 %), permanent morbidity >mRS 1 in 3 (4.3 %) grade 1 and 2, four (18 %) grade 3, and three (50 %) grade 4. Treatment inflicted loss of QALY amounted to 0.5 years for SM grade 1-2, 2.5 years grade 3, 7.3 years for grade 4. For the SM grades 1 and 2, the treatment related loss of 0.5 QALY was met by the natural course after 2.7-4.3 years. For the Spetzler-Martin grades 3 and 4, the treatment-induced loss QALY was not met by the natural risk within a foreseeable time. Permanent morbidity and treatment inflicted loss of QALY of patients younger than 39 years was lower than that of older patients (7 vs. 15 % and 1.0 vs. 2.1 QALY). CONCLUSIONS: Microsurgically managed SM grades 1 and 2 fared better than the modeled natural course but grades 3 and 4 AVM did not benefit from surgery. Younger patients appear to fare more favorably than older patients. PMID- 26144567 TI - Anterior cervical discectomy and fusion versus posterior cervical foraminotomy in the treatment of brachialgia: the Leeds spinal unit experience (2008-2013). AB - BACKGROUND: The surgical management of cervical brachialgia utilising anterior cervical discectomy and fusion (ACDF) or posterior cervical foraminotomy (PCF) is a controversial area in spinal surgery. Previous studies are limited by utilisation of non-validated outcome measures and, importantly, absence of pre operative analysis to ensure both groups are matched. The authors aimed to compare the effectiveness of ACDF and PCF using validated outcome measures. To our knowledge, it is the first study in the literature to do this. METHODS: The authors conducted a 5-year retrospective review (2008-2013) of outcomes following both the above procedures and also compared the effectiveness of both techniques. Patients with myelopathy and large central discs were excluded. The main outcome variables measured were the neck disability index (NDI) and visual analogue scores (VAS) for neck and arm pain pre-operatively and again at 2-year follow-up. The Wilcoxon signed-rank test and Student t-tests were used to test differences. RESULTS: A total of 150 ACDFs and 51 PCFs were performed for brachialgia. There was no differences in the pre-operative NDI, VAS neck and arm scores between both groups (p > 0.05). As expected, both ACDF and PCF delivered statistically significant improvement in NDI, VAS-neck and VAS-arm scores. The degree of improvement of NDI, VAS-neck and VAS-arm were the same between both groups of patients (p > 0.05) with a trend favouring the PCF group. In the ACDF group, two (1.3 %) patients needed repeat ACDF due to adjacent segment disease. One patient (0.7 %) needed further decompression via a foraminotomy. In the PCF group one (2.0 %) patient needed ACDF due to persistent brachialgia. CONCLUSIONS: We found both interventions delivered similar improvements in the VAS and NDI scores in patients. Both techniques may be appropriately utilised when treating a patient with cervical brachialgia. PMID- 26144568 TI - Pharmacogenetics of Asthma. PMID- 26144569 TI - Erratum to: The Face of Lysosomal Storage Disorders in India: A Need for Early Diagnosis. PMID- 26144570 TI - Instability of IGF-IGFBP complex as a cause of the different performance of serum and EDTA-plasma after storage: EDTA-plasma is preferable for evaluating bioactive IGF especially in the mouse. AB - OBJECTIVE: The insulin-like growth factor (IGF) signaling pathway is recognized as a potential target for treating several cancers, and strategies targeting the IGF type 1 receptor (IGF-1R) have been evaluated in many clinical trials. These suggested that the pretreatment level of circulating free IGF gives an estimate of IGF bioactivity and might be a predictive biomarker of the response to anti IGF-1R antibodies. However, there is no defined protocol for measuring free and bioactive IGF concentrations, partly because the measurement procedures, including sample collection and handling, have not been standardized. We investigated the effects of sample collection methods and storage conditions on bioactive IGF measurement using a modified kinase receptor activation (KIRA) assay in human and mouse samples. DESIGN: Blood samples were obtained from healthy men and women, and from healthy male and female wild-type BALB/c mice. Serum and ethylenediaminetetraacetic acid (EDTA)-plasma samples were collected and used immediately or stored in small quantities at 4 degrees C or -80 degrees C for 3, 7, or 14 days. A bioassay directed against the phosphorylated IGF-1R using western blot analysis was developed as a modification of the KIRA assay, in which the level of phosphorylation of IGF-1R represented the IGF bioactivity in blood samples. RESULTS: The levels of bioactive IGFs in mouse serum stored at 4 degrees C increased markedly in a time-dependent manner; the increase was slightly reduced in samples stored at -80 degrees C. Analysis of mouse EDTA-plasma stored at 4 degrees C showed a similar pattern, but the time dependent increase was less than in the serum samples. By contrast, the levels of bioactive IGFs in EDTA-plasma stored at -80 degrees C were stable over 14 days. The levels of human bioactive IGFs in both serum and EDTA-plasma stored at 4 degrees C increased slightly with time, but the increases were much smaller than in mouse samples. The levels of human bioactive IGF in both serum and EDTA-plasma stored at -80 degrees C were stable over 14 days. CONCLUSIONS: The use of EDTA plasma avoids the problems with long-term storage. Therefore, EDTA-plasma should be used when measuring circulating IGF bioactivity, especially in mouse samples. All samples should be stored at -80 degrees C when long-term storage is unavoidable. Because of the large difference in the stability of the IGF-IGF binding protein complex between the human and mouse in vitro, all samples should be handled carefully to ensure the accurate evaluation of IGF bioactivity, especially in mouse samples. PMID- 26144571 TI - A split-mouth, randomized, triple-blind, placebo-controlled study to analyze the pre-emptive effect of etoricoxib 120 mg on inflammatory events following removal of unerupted mandibular third molars. AB - Pain after third molar extraction has been considered the most suitable pharmaceutical model to evaluate acute pain. This study aimed to evaluate the pre emptive analgesic/anti-inflammatory efficacy of etoricoxib 120 mg following mandibular third molar surgery. A split-mouth, randomized, triple-blind, placebo controlled study was conducted with patients undergoing the surgical removal of mandibular third molars. All volunteers were allocated randomly to receive either etoricoxib 120 mg or placebo 1h preoperatively, and inflammatory events were evaluated. An estimated sample of 18 surgical units per group was required based on a pilot study (95% confidence level and 80% statistical power). Rescue medication was analyzed by Kaplan-Meier method through log-rank Mantel-Cox test and Pearson linear correlation (P<0.05). Pre-emptive etoricoxib reduced postoperative pain scores significantly in comparison to placebo (P<0.001), with a pain score peak at 6h after surgery (P<0.001). The mean rescue medication consumption was lower in the etoricoxib group compared to the placebo group over the study period (P<0.05). There was no statistically significant difference between groups related to swelling and trismus. The pre-emptive administration of etoricoxib 120 mg significantly reduced the postoperative pain intensity and the need for rescue medication, but did not reduce swelling or trismus. PMID- 26144572 TI - Dynamics of expression and localization of the cannabinoid system in granulosa cells during oocyte nuclear maturation. AB - OBJECTIVE: To describe the expression of cannabinoid receptors CB1 and CB2 and cannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGLL) in human granulosa cells and to investigate their differential distribution with respect to CB1 at various stages during the nuclear maturation of the oocyte. DESIGN: Analysis of granulosa cells from germinal vesicle (GV), metaphase I (MI), and MII oocytes by quantitative reverse transcriptase polymerase chain reaction, Western blot, and indirect immunofluorescence assays. SETTING: Academic research laboratory. PATIENT(S): Patients from the Human Reproduction Unit of Cruces University Hospital undergoing intracytoplasmic sperm injection. INTERVENTION(S): We analyzed the granulosa cells of 300 oocytes from 53 patients. The oocyte maturation stages were 75 at GV stage, 51 at MI, and 174 at MII. MAIN OUTCOME MEASURE(S): The mRNA and protein expression of CB1, CB2, FAAH, and MGLL and localization in granulosa cells at each oocyte maturation stage. RESULT(S): CB1, FAAH, and MGLL are present in human granulosa cells during oocyte maturation, but the presence of CB2 receptor is not entirely clear in those cells. CB1 and FAAH were detected in the periphery of the granulosa cells from the GV to the MII oocytes, and they colocalized in some portions of the cell membrane. On the other hand, MGLL immunostaining was more homogeneous across the cell and overlapped with CB1 only weakly. CONCLUSION(S): The presence of the cannabinoid system in granulosa cells suggests a possible role of this system in the nuclear maturation of the oocyte. PMID- 26144573 TI - Antimullerian hormone as a predictor of good-quality supernumerary blastocyst cryopreservation among women with levels <1 ng/mL versus 1-4 ng/mL. AB - OBJECTIVE: To determine whether antimullerian hormone (AMH) levels predict the availability of good-quality supernumerary blastocysts for cryopreservation. DESIGN: Retrospective study. SETTING: Two fertility centers. PATIENT(S): First fresh IVF cycles (n = 247) grouped as follows: 40 women <35 year old with AMH <1 ng/mL and 77 women with AMH 1-4 ng/mL; 62 women >=35 year old with AMH <1 ng/mL, and 68 women with AMH 1-4 ng/mL. INTERVENTION(S): AMH level measured before IVF with ovarian stimulation protocols based on patient age and AMH level, including short gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, or GnRH agonist microdose flare; supernumerary good-quality blastocysts cryopreserved on days 5 or 6 after retrieval. MAIN OUTCOME MEASURES(S): Supernumerary good-quality blastocysts for cryopreservation in relation to AMH levels. RESULT(S): Among women <35 years of age, there was a statistically significant difference in the number of patients with supernumerary good-quality blastocysts for cryopreservation between the groups with AMH <1 ng/mL and AMH 1-4 ng/mL (30.0% vs. 58.4%) when adjusted for age. Among women >=35 years of age, there was a statistically significant difference in the number of patients with supernumerary good-quality blastocyst cryopreservation between groups with AMH <1 ng/mL and AMH 1-4 ng/mL (16.1% vs. 42.6%), when adjusted for age. CONCLUSION(S): Low AMH levels are associated with a statistically significantly lower likelihood of blastocysts for cryopreservation as compared with higher AMH levels. This effect was seen among women both <35 and >=35 years of age. Patient counseling should include realistic expectations for the probability of good-quality supernumerary blastocysts available for cryopreservation. PMID- 26144574 TI - Relationship of paternal age with outcome of percutaneous epididymal sperm aspiration-intracytoplasmic sperm injection, in cases of congenital bilateral absence of the vas deferens. AB - OBJECTIVE: To assess the relationship between paternal age and the outcome of percutaneous epididymal sperm aspiration-intracytoplasmic sperm injection (ICSI) in patients with congenital bilateral absence of the vas deferens (CBAVD). DESIGN: Prospective cohort study. SETTING: In vitro fertilization centers. PATIENT(S): Eighty-five (male) CBAVD patients who underwent percutaneous epididymal sperm aspiration with ICSI were divided into 3 age groups; <30 years (n = 27); aged 30-40 years (n = 32); and aged >40 years (n = 26). INTERVENTION(S): History taking, clinical examination, semen analysis, percutaneous epididymal sperm aspiration with subsequent ICSI. MAIN OUTCOME MEASURE(S): Sperm retrieval, clinical pregnancy, and "take-home baby." RESULT(S): The number of sperm retrieved by percutaneous epididymal sperm aspiration significantly decreased with advancing age in the studied groups (0.63, 0.31, and 0.18 million, respectively), concomitant with significant decreases in the outcomes of clinical pregnancy (55.5%, 43.7%, and 23.1%, respectively) and "take home baby" (48.1%, 40.6%, and 11.5%, respectively). Male age was significantly negatively correlated with retrieved sperm count, sperm motility, sperm vitality, and normal sperm morphology. Multiple logistic regression, adjusted for confounding factors, with male age, and sperm count obtained using percutaneous epididymal sperm aspiration, was significant. The receiver operating characteristic curve showed that a sperm count of 0.55 million as a cutoff value could predict clinical pregnancy with an accuracy of 77.4%, with 82.9% sensitivity and 62% specificity, and "take-home baby" with an accuracy of 81.7%, with 93.1% sensitivity and 62.5% specificity. CONCLUSION(S): In cases of CBAVD, male age has a negative effect on retrieved-sperm count, motility, vitality, and normal sperm morphology; number of retrieved sperm predicted both clinical pregnancy and "take-home baby" outcomes in subsequent ICSI. PMID- 26144575 TI - Automated versus Manual Oxygen Control with Different Saturation Targets and Modes of Respiratory Support in Preterm Infants. AB - OBJECTIVE: To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (FiO2) in maintaining arterial oxygen saturation (SpO2) within a higher (91%-95%) and a lower (89%-93%) target range in preterm infants. STUDY DESIGN: Eighty preterm infants (gestational age [median]: 26 weeks, age [median] 18 days) on noninvasive (n = 50) and invasive (n = 30) respiratory support with supplemental oxygen, were first randomized to one of the SpO2 target ranges and then treated with automated FiO2 (A-FiO2) and manual FiO2 (M-FiO2) oxygen control for 24 hours each, in random sequence. RESULTS: The percent time within the target range was higher during A-FiO2 compared with M FiO2 control. This effect was more pronounced in the lower SpO2 target range (62 +/- 17% vs 54 +/- 16%, P < .001) than in the higher SpO2 target range (62 +/- 17% vs 58 +/- 15%, P < .001). The percent time spent below the target or in hypoxemia (SpO2 <80%) was consistently reduced during A-FiO2, independent of the target range. The time spent above the target range or at extreme hyperoxemia (SpO2 >98%) was only reduced during A-FiO2 when targeting the lower SpO2 range (89% 93%). These outcomes did not differ between infants on noninvasive and invasive respiratory support. Manual adjustments were significantly reduced during A-FiO2 control. CONCLUSIONS: A-FiO2 control improved SpO2 targeting across different SpO2 ranges and reduced hypoxemia in preterm infants on noninvasive and invasive respiratory support. TRIAL REGISTRATION: ISRCTN 56626482. PMID- 26144576 TI - Health-related quality of life evaluated by Pediatric Quality of Life Inventory 4.0 in pediatric leprosy patients with musculoskeletal manifestations. AB - OBJECTIVE: To evaluate the health-related quality of life (HRQL) in pediatric leprosy patients. METHODS: A cross-sectional study included 47 leprosy patients and 45 healthy subjects. The HRQL was measured by Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0), and evaluated physical, emotional, social and school domains. The leprosy patients were classified by Ridley and Jopling classification criteria and assessed according to clinical musculoskeletal manifestations, laboratory and radiographic examinations. RESULTS: The median of current age was similar in leprosy patients and controls [12(6-18) vs. 15(5 18)years, p = 0.384], likewise the frequencies of female gender (p = 0.835) and middle/lower Brazilian socio-economic classes (p = 1.0). The domain school activities according the child-self report was significantly lower in leprosy patients compared to controls in the age group of 13-18 years [75(45-100) vs. 90(45-100), p = 0.021]. The other domains were alike in both groups (p > 0.05). At least one musculoskeletal manifestation (arthralgia, arthritis and/or myalgia) was observed in 15% of leprosy patients and none in controls (p = 0.012). Further comparison between all leprosy patients showed that the median of the physical capacity domain [81.25(50-100) vs. 98.44(50-100), p = 0.036] and school activities domain by child-self report [60(50-85) vs. 80(45-100), p = 0.042] were significantly lower in patients with musculoskeletal manifestations compared to patients without these manifestations. No differences were evidenced between the other HRQL parameters in both groups, reported by patients and parents (p > 0.05). CONCLUSIONS: Reduced physical capacity and school activities domains were observed in pediatric leprosy patients with musculoskeletal manifestations. PMID- 26144577 TI - Association between the COMT gene and neurological abnormalities and poorer executive function in psychosis. PMID- 26144578 TI - The association of non-suicidal self-injury and suicidal behavior according to DSM-5 in adolescent psychiatric inpatients. AB - Non-suicidal self-injury (NSSI) and suicidal behaviors frequently occur among adolescent psychiatric patients. Although those behaviors are distinct with regards to intent, NSSI has been shown to be an important risk-factor for suicide attempts. However, the association of NSSI and Suicidal Behavior Disorder (SBD) according to DSM-5 criteria has not yet been investigated. For investigating distinctive features and mutual risk-factors of NSSI-disorder and SBD, adolescent psychiatric inpatients (N=111, aged 12-19 years; 65.8% females) were interviewed using the Self-Injurious-Thoughts-And-Behaviors-Interview-German (SITBI-G). NSSI started significantly earlier in life (M=12.5 years, SD=2.2) than first suicide attempts (M=14.1 years, SD=2.0). Patients meeting NSSI-disorder and/or SBD were significantly more likely to be female and to be diagnosed with an affective disorder. NSSI-disorder and SBD seem to have several distinctive features (i.e. age of onset or frequency), but also seem to share certain mutual risk-factors (i.e. affective disorders, female gender). While both NSSI and SBD seem to be maintained by mainly automatic negative reinforcement, positive automatic and social functions were rated significantly higher for NSSI. Most importantly, NSSI seems to be a strong risk factor for the occurrence of SBD (even when controlling for suicidal ideation) and should therefore always be assessed when dealing with psychiatric adolescent patients. PMID- 26144579 TI - Metabolic factors-triggered inflammatory response drives antidepressant effects of exercise in CUMS rats. AB - Chronic stress is a potential contributing factor for depression, accompanying with metabolic and inflammatory response. Exercise is considered as a treatment for depression, but mechanisms underlying its beneficial effects still remain unknown. The objectives of present study were to confirm that metabolic factors triggered inflammatory response mediates the antidepressant actions of exercise in chronic unpredictable mild stress (CUMS) rats. It has been found that CUMS stimulated expression of ghrelin and its receptor Ghsr, but inhibited expression of leptin and its receptor LepRb. Ghrelin, via binding to Ghsr, induced phosphorylation of GSK-3beta on Tyr216 and decreased phosphorylation on Ser9, thus increasing GSK-3beta activity. Conversely, ghrelin binding to Ghsr decreased STAT3 activity, through decreasing phosphorylation of STAT3 on Tyr705 and increasing Ser727 phosphorylation. Negatively correlated with ghrelin, leptin binding to LepRb had opposite effects on the activity of GSK-3beta and STAT3 via phosphorylation. In addition, decreased leptin level initiated NLRP3 activity via LepRb. Furthermore, GSK-3beta inhibited STAT3 activation, thus promoting the expression of NLRP3. Meanwhile, swim improved metabolic and inflammatory response both in CUMS and control rats. Our findings suggest that exercise not only ameliorates metabolic disturbance and inflammatory response in depression, but also contributes to metabolic and inflammatory function in normal conditions. PMID- 26144580 TI - The influence of eating psychopathology on autobiographical memory specificity and social problem-solving. AB - The primary aim was to examine the influence of subclinical disordered eating on autobiographical memory specificity (AMS) and social problem solving (SPS). A further aim was to establish if AMS mediated the relationship between eating psychopathology and SPS. A non-clinical sample of 52 females completed the autobiographical memory test (AMT), where they were asked to retrieve specific memories of events from their past in response to cue words, and the means-end problem-solving task (MEPS), where they were asked to generate means of solving a series of social problems. Participants also completed the Eating Disorders Inventory (EDI) and Hospital Anxiety and Depression Scale. After controlling for mood, high scores on the EDI subscales, particularly Drive-for-Thinness, were associated with the retrieval of fewer specific and a greater proportion of categorical memories on the AMT and with the generation of fewer and less effective means on the MEPS. Memory specificity fully mediated the relationship between eating psychopathology and SPS. These findings have implications for individuals exhibiting high levels of disordered eating, as poor AMS and SPS are likely to impact negatively on their psychological wellbeing and everyday social functioning and could represent a risk factor for the development of clinically significant eating disorders. PMID- 26144581 TI - Clinical correlates of obsessive-compulsive symptom dimensions in at-risk mental states and psychotic disorders at early stages. AB - We studied the clinical correlates of obsessive-compulsive symptom dimensions in 109 individuals with early psychosis (31 At-Risk Mental States [ARMS], 78 psychotic disorders with <3 years of illness) and 59 healthy subjects. Obsessive compulsive symptoms were assessed by the Obsessive-Compulsive Inventory - Revised. We also assessed the severity of psychotic symptoms, depressive symptoms and functioning. ARMS and psychotic disorder patients reported more obsessive compulsive symptoms than did healthy subjects. The ARMS individuals also reported more overall and checking obsessive-compulsive symptoms compared with the PD patients. Different types of obsessive-compulsive symptoms were related with depressive symptoms in both diagnostic groups. However, a different pattern was observed in the relationship between obsessive-compulsive dimensions and functioning by diagnosis (better functioning in ARMS; poorer functioning in psychotic disorders). Our study suggests that obsessive-compulsive symptoms are present in the early stages of psychotic illness, as well as in individuals at risk for psychosis. Future prospective studies are needed to elucidate how obsessive-compulsive symptoms in ARMS may influence the prognosis in terms of global functioning and the risk of psychosis transition. PMID- 26144582 TI - Risk factors for incident depression in patients at first acute coronary syndrome. AB - The association between depression and acute coronary syndrome (ACS) is well established and the first seems to impact meaningfully on cardiac prognosis. Nonetheless only a few studies have evaluated the relationship between incident depression, defined as new cases in patients with no history of depression, and ACS. Therefore the aim of this study is to analyse the risk factors of incident depression in a sample of patients who were presenting their first ACS. 304 consecutive patients were recruited. The presence of major (MD) and minor (md) depression was assessed with the Primary Care Evaluation of Mental Disorders (PRIME-MD), whereas its severity was evaluated with the Hospital Anxiety and Depression Scale (HADS). Evaluations were collected both at baseline and at 1, 2, 4, 6, 9 and 12 month follow ups. Out of 304 subjects (80.6% males), MD was diagnosed in 15 (4.9%) and md in 25 patients (8.2%). At baseline risk factors for a post-ACS depressive disorder were being women (MD only), widowed (md only) and having mild anhedonic depressive symptoms few days after the ACS. Clinicians should keep in mind these variables when facing a patient at his/her first ACS, given the detrimental effect of depression on cardiac prognosis. PMID- 26144583 TI - Interpersonal reactivity differences in Tourette syndrome. AB - Tourette syndrome (TS) frequently involves complex tics with social significance, including imitation or socially inappropriate behaviour. This study explored every-day perspective taking and empathic tendencies in 95 patients with TS and 60 healthy controls. Analyses indicated that both males and females with TS exhibited a different interpersonal reactivity profile to controls, characterised by a reduced tendency to take other people's perspectives, and elevated personal distress in response to intense emotional situations (e.g. people experiencing crises). PMID- 26144584 TI - Examining neurocognition in body dysmorphic disorder using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): A comparison with obsessive-compulsive disorder. AB - Body dysmorphic disorder (BDD) is characterised by (i) an excessive preoccupation with an imagined defect in appearance, as well as (ii) repetitive behaviours and/or mental acts that occur in response to the preoccupation. To date, neuropsychological investigations have been limited. This study examined performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), tapping into five indices of neurocognition: (i) Immediate Memory, (ii) Visuospatial Construction, (iii) Language, (iv) Attention, and (iv) Delayed Memory. Twenty-one BDD participants were compared with 19 obsessive compulsive disorder (OCD) participants and 21 healthy controls (HC), who were age , sex-, and IQ-matched. Results indicated the BDD and OCD groups demonstrated poor overall neuropsychological performance (i.e. total RBANS) as well as deficits on the indices of Immediate Memory and Attention. Further group differences involving the subtests of Story Memory, Digit Span, and Story Recall were detected. Neuropsychological impairment in BDD with indicated similarities in OCD were corroborated. Future research should extend investigations focusing on gist and delayed memory, and aspects of attentional processing. PMID- 26144585 TI - The effects of childhood abuse on self-reported psychotic symptoms in severe mental illness: Mediating effects of posttraumatic stress symptoms. AB - The present study examined the role of posttraumatic stress symptoms in the relationship between childhood abuse and self-reported psychotic symptoms in severe mental illness. A total of 126 patients diagnosed with major psychiatric conditions with comorbid symptoms of psychosis participated in the present study. The representative psychiatric diagnoses included schizophrenia, bipolar disorder with psychotic features, major depressive disorder with psychotic features, schizoaffective disorder, schizophreniform disorder, and delusional disorder. The Korean Child Trauma Questionnaire measured the type and degree of childhood abuse including emotional, physical, and sexual abuse. Korean version of the Impact of Event Scale-Revised assessed posttraumatic stress symptoms, and PSYC subscale of the PSY-5 Factor Scale of the MMPI-2 was used as a measure of self-reported psychotic symptoms. There was a significant relationship between childhood physical, emotional, sexual abuse and psychotic symptoms. Posttraumatic stress symptoms partially mediated the relationship between childhood abuse and psychotic symptoms. This implies that childhood abuse is significantly associated with the experience of chronic posttraumatic stress symptoms, and that such symptoms in turn increases the likelihood of experiencing psychotic symptoms. The results highlight the need for appropriate assessment and intervention concerning childhood abuse and posttraumatic stress symptoms in severe mental illness. PMID- 26144586 TI - Personality in male patients with substance use disorder and/or severe mental illness. AB - Dual diagnosis (DD) is the coexistence of a substance use disorder (SUD) and severe mental illness (SMI). The aim of this study is to determine for the first time if a specific personality pattern exists for DD patients compared to those who only have SUD or SMI. The sample was composed of 102 male, 34 patients in each group (DD, SUD and SMI). DD and SMI groups included 20 schizophrenic and 14 depressed patients respectively. Cloninger's TCI-R was administered together with a structured interview of sociodemographic and clinical characteristics. All the temperament dimensions and Self-directedness provided differences among groups. The DD and SUD showed significant higher scores in Novelty Seeking regarding SMI, whereas for Harm Avoidance the SUD subjects scored lower with respect to the DD and SMI group. Persistence was significant lower for the DD and SMI groups compared to the SUD patients. The DD obtained low significant scores in Reward Dependence in relation to the SUD and Self-directedness in relation to the SUD and SMI. Our data highlight the presence of a different personality profiles among DD, SUD and SMI disorders. Taking into account the patients' personality can benefit the clinical course and minimize the DD impact. PMID- 26144587 TI - Impaired conflict resolution and vigilance in euthymic bipolar disorder. AB - Difficulty attending is a common deficit of euthymic bipolar patients. However, it is not known whether this is a global attentional deficit or relates to a specific attentional network. According to the attention network approach, attention is best understood in terms of three functionally and neuroanatomically distinct networks-alerting, orienting, and executive control. In this study, we explored whether and which of the three attentional networks are altered in euthymic Bipolar Disorder (BD). A sample of euthymic BD patients and age-matched healthy controls completed the Attention Network Test for Interactions and Vigilance (ANTI-V) that provided not only a measure of orienting, executive, and alerting networks, but also an independent measure of vigilance (tonic alerting). Compared to healthy controls, BD patients have impaired executive control (greater interference), reduced vigilance (as indexed by a decrease in the d' sensitivity) as well as slower overall reaction times and poorer accuracy. Our results show that deficits in executive attention and sustained attention often persist in BD patients even after complete remission of affective symptoms, thus suggesting that cognitive enhancing treatments programmed to improve these deficits could contribute to improve their functional recovery. PMID- 26144588 TI - The dimensional structure of cycling mood disorders. AB - This study examines whether mood disorders differ fundamentally in terms of phase duration. Most clinically significant mood disorders are recurrent and cyclical. The phase duration of these cycles is part of the diagnostic criteria. Specifically, we determined whether a dimensional or taxonic latent structure better captures cycling mood disorders. 319 patients recruited from 5 psychiatrists and a psychoeducational program completed three questionnaires assessing aspects of mood cycling. These were the Affective Lability Scale-Short Form (ALS-SF), Mood Disorders Questionnaire (MDQ), and the Eysenck Neuroticism scale. Patient scores on these instruments were submitted to three taxometric procedures (MAMBAC, MAXEIG, and L-Mode). Comparison curve fit indices (CCFIs) were calculated to distinguish taxonic versus dimensional latent structure. In addition, graphs were produced for each procedure and compared with those of categorical or dimensional prototypes. The CCFIs of the three procedures ranged from 0.25 to 0.27, consistent with dimensional structure. The graphs closely resembled dimensional prototypes. Mood instability and other types of cycling moods probably conform to a dimensional latent structure. Patients with disorders featuring mood cycling might benefit from common treatments. PMID- 26144589 TI - In vivo confocal microscopy and spectral domain anterior segment OCT in Lisch epithelial corneal dystrophy. PMID- 26144590 TI - [Uveitis associated with nephrotic syndrome: Initial manifestations of secondary syphilis]. PMID- 26144591 TI - [Acute sectorial choroidal ischemia secondary to primary polycythemia vera]. PMID- 26144592 TI - Sexual risk behaviors and steroid use among sexual minority adolescent boys. AB - BACKGROUND: Previous research has extensively examined the relationship between the use of alcohol and illicit substances with sexual risk behaviors among sexual minority (i.e., gay and bisexual) male youth; however, no known studies have assessed the association of steroid use to risk behaviors among this population. METHODS: Participants were 556 sexually active sexual minority adolescent boys (M age=16.2, SD=1.3), taken from a pooled dataset of the 14 jurisdictions from the 2005 and 2007 Youth Risk Behavior Surveys that assessed sexual orientation. The association between lifetime use of steroids and sexual risk behaviors were examined. RESULTS: Controlling for number of sexual partners, depression, victimization, and race, boys who reported increased steroid use were at increased odds of engaging in condomless sex, OR=1.55, p=.003, and use of alcohol/drugs during sex, OR=1.48, p=.002. CONCLUSIONS: Steroid use among sexual minority adolescent boys is prevalent and associated with HIV/STI sexual transmission risk behaviors. PMID- 26144593 TI - Cannabis effects on driving lateral control with and without alcohol. AB - BACKGROUND: Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aim to determine how blood Delta(9)-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol. METHODS: Current occasional (>=1*/last 3 months, <=3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (~0.8h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17h, 0.42h) and after (1.4h, 2.3h) driving that occurred 0.5-1.3h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration. RESULTS: In N=18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1MUg/L during driving increased SDLP similar to 0.05 and 0.08g/210L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5MUg/L THC+0.05g/210L alcohol showing similar SDLP to 0.08g/210L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples. CONCLUSIONS: SDLP was a sensitive cannabis related lateral control impairment measure. During drive blood THC >=8.2MUg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation. PMID- 26144595 TI - Immunogenicity assessment of biotherapeutic products: An overview of assays and their utility. AB - Biotherapeutic products (BTPs) are the fastest growing medicines in the pharmaceutical market. Despite their clinical success, the immunogenicity of BTPs continues to be a major concern. Assessment of immunogenicity as well as appropriate interpretation of immunogenicity data is therefore, of critical importance for defining safety profile of these products for the purpose of their licensure and use. In the past decade, much progress has been made towards how immunogenicity should be studied. This article reflects the content of the brief presentation on principles of methods used for immunogenicity assessment and their merits and limitations given at the first World Health Organization (WHO) implementation workshop on rDNA derived biotherapeutic products held in the Republic of Korea in May 2014 to support the case studies on immunogenicity presented and discussed during the workshop. The purpose of this article is to provide an overview of the methods used for assessing immunogenicity of biotherapeutic products (BTPs) and the most important considerations in interpreting results in the context of regulatory overview of these products. PMID- 26144594 TI - Lipid derivatives activate GPR119 and trigger GLP-1 secretion in primary murine L cells. AB - AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) is an incretin hormone derived from proglucagon, which is released from intestinal L-cells and increases insulin secretion in a glucose dependent manner. GPR119 is a lipid derivative receptor present in L-cells, believed to play a role in the detection of dietary fat. This study aimed to characterize the responses of primary murine L-cells to GPR119 agonism and assess the importance of GPR119 for the detection of ingested lipid. METHODS: GLP-1 secretion was measured from murine primary cell cultures stimulated with a panel of GPR119 ligands. Plasma GLP-1 levels were measured in mice lacking GPR119 in proglucagon-expressing cells and controls after lipid gavage. Intracellular cAMP responses to GPR119 agonists were measured in single primary L-cells using transgenic mice expressing a cAMP FRET sensor driven by the proglucagon promoter. RESULTS: L-cell specific knockout of GPR119 dramatically decreased plasma GLP-1 levels after a lipid gavage. GPR119 ligands triggered GLP 1 secretion in a GPR119 dependent manner in primary epithelial cultures from the colon, but were less effective in the upper small intestine. GPR119 agonists elevated cAMP in ~70% of colonic L-cells and 50% of small intestinal L-cells. CONCLUSIONS/INTERPRETATION: GPR119 ligands strongly enhanced GLP-1 release from colonic cultures, reflecting the high proportion of colonic L-cells that exhibited cAMP responses to GPR119 agonists. Less GPR119-dependence could be demonstrated in the upper small intestine. In vivo, GPR119 in L-cells plays a key role in oral lipid-triggered GLP-1 secretion. PMID- 26144596 TI - Isolation of the neutralization ScFvs Against HBV infection from the Immunized Population. AB - For a long time, researchers have attempted to replace human plasmaderived immunoglobulin against HBV with recombinant HBV antibodies for therapeutic purposes, but failed to develop the products. One of the reasons may be lack of high throughput antibody screening tool. In this study, we screened an antibody library from immunized subjects by a powerful bacterial display technology. The capacity of the ScFv library was 10(9), 117 individual clones against HBV pre- S1 were initially selected and sequenced, the homology of these clones ranged from 59.7% -68.7%. Ten clones were randomly selected based on florescence intensity by FACS. The ScFv antibodies were expressed in E.coli and purified to examine their neutralization ability. First, we tested the ability of these clones to block the binding of the pre-S1 polypeptide to the HBV sensitive cells Chang liver cells and HepG2 cells, then, we examined the ability of these clones to inhibit the infection of the Change liver cells by HBV released from HepG2.2.15 cells by detection of viral DNA and hepatitis B virus e antigen (HBeAg) in the supernatant of Chang liver cells. Results showed that 4 (clone 3, 7, 9 and 31) out of the ten clones could significantly reduce the binding of pre-S1 polypeptide to Chang liver cells in a dose-dependent manner. Treatment with the same clones (clone 3, 7, 9 and 31) could dramatically reduce the contents of HBV DNA in the media of the infected Chang liver cells by 29.4, 7.89, 58.8, 76.9, respectively, and the amount of HBeAg by 60.2%, 32.6%, 66.1% and 68.1%, respectively. These results suggest that these clones can neutralize HBV infection and have the potential to become therapeutic antibodies against HBV infection to replace the human plasma derived immunoglobulin. PMID- 26144597 TI - Graduate midwives' perception of their preparation and support in using evidence to advocate for women's choice: A Western Australian study. AB - A retrospective cohort study was conducted with 83 midwives working across the Western Australian (WA) maternity sector who graduated from one WA University. We explored midwives' attitudes and utilisation of research and assertive communication in addition to perceptions of their educational preparation to advocate for women. The greatest opportunity for research exposure was working on a clinical audit (25.3%). No differences were found between graduate groups using the Edmonton Research Orientation subscales, although findings suggest a positive view towards research. Midwives were more likely to be assertive with their clinical colleagues than a midwifery manager or medical colleague when: expressing their opinions (P = <0.001); saying no (P = <0.001); allowing others to express their opinions (P = <0.001); and making suggestions to others (P = 0.025). A qualitative phase with 15 midwives explored concepts around advocating for women. Four themes emerged: 'having the confidence to question', 'communication skills', work environment' and 'knowing the woman and what she wants'. Findings suggest strategies are needed in their entry to practice preparation and ongoing professional development to facilitate research engagement. Using assertive behaviour to provide feedback to clinical colleagues warrants attention to enhance reflective practice. Building communication skills through observing positive role models and participating in role play was highlighted. PMID- 26144598 TI - Elementary school students' perceptions of stuttering: A mixed model approach. AB - PURPOSE: Past research studies have focused on perceptions of stuttering by various age groups and only a few have examined how children react to a peer who stutters. All of these studies used a quantitative analysis but only one included a qualitative analysis of elementary school age children's responses to stuttering. The aim of this study was to further explore the perceptions of elementary school students toward a peer who stutters using both quantitative and qualitative analyses of three levels of stuttering. METHODS: Participants included 88 elementary school children between 8 and 12 years of age. Each participant viewed one of four audiovisual samples of a peer producing fluent speech and mild, moderate, and severe simulated stuttering. Each participant then rated five Likert statements and answered three open-ended questions. RESULTS: Quantitative and qualitative results indicated that negative ratings and the percentage of negative comments increased as the frequency of stuttering increased. However, the children in this study indicated that they were comfortable listening to stuttering and would be comfortable making friends with the peer who stutters. CONCLUSION: The findings of this study together with past research in this area should help clinicians and their clients appreciate the range of social and emotional reactions peers have of a child who stutters. EDUCATIONAL OBJECTIVES: After reading this article, the reader will be able to: (a) discuss past research regarding children's perceptions of stuttering; (b) summarize the need to explore the perceptions of elementary-aged children toward a peer who stutters; (c) describe the major quantitative and qualitative findings of children's perceptions of stuttering; and (d) discuss the need for disseminating more information about stuttering to children and teachers. PMID- 26144599 TI - Role of the GH-IGF-1 system in Atlantic salmon and rainbow trout postsmolts at elevated water temperature. AB - A comparative experiment with Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) postsmolts was conducted over 35 days to provide insight into how growth, respiration, energy metabolism and the growth hormone (GH) and insulin-like growth factor 1 (IGF-1) system are regulated at elevated sea temperatures. Rainbow trout grew better than Atlantic salmon, and did not show reduced growth at 19 degrees C. Rainbow trout kept at 19 degrees C had increased blood hemoglobin concentration compared to rainbow trout kept at 13 degrees C, while salmon did not show the same hemoglobin response due to increased temperature. Both species showed reduced length growth and decreased muscle glycogen stores at 19 degrees C. Circulating IGF-1 concentration was higher in rainbow trout than in Atlantic salmon, but was not affected by temperature in either species. Plasma IGF-binding protein 1b (IGFBP-1b) concentration was reduced in Atlantic salmon reared at 19 degrees C after 15 days but increased in rainbow trout at 19 degrees C after 35 days. The igfbp1b mRNA level in liver showed a positive correlation to plasma concentrations of glucose and IGFBP-1b, suggesting involvement of this binding protein in carbohydrate metabolism at 19 degrees C. At this temperature muscle igfbp1a mRNA was down-regulated in both species. The muscle expression of this binding protein correlated negatively with muscle igf1 and length growth. The plasma IGFBP-1b concentration and igfbp1b and igfbp1a expression suggests reduced muscle igf1 signaling at elevated temperature leading to glucose allostasis, and that time course is species specific due to higher thermal tolerance in rainbow trout. PMID- 26144600 TI - Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients. AB - BACKGROUND: To compare the efficacy of chemotherapy (C) combined with bevacizumab (Bev) versus Bev alone in recurrent, heavily pretreated epithelial ovarian cancer (EOC). METHODS: A multicenter analysis of patients treated from 2004 to 2011 was performed. Demographic, treatment, response, and adverse event information were obtained. Progression-free (PFS) and overall survival (OS) were analyzed. RESULTS: Of 277 patients (median age: 58years), the majority had Stage III and IV (86%) disease, and 72% had serous histology. 244 (88%) were treated with C+Bev and 33 (12%) with Bev. Corresponding median progression-free survival (PFS) was 8.7 and 6.7months, and median overall survival (OS) was 14.3 and 10.5months, respectively. The chemotherapeutic agents combined with Bev and the median OS include: pegylated liposomal doxorubicin (n=19, OS of 20.4months), taxanes (n=55, OS of 20.2months), gemcitabine (n=106, OS of 14.1months), topotecan (n=43, OS of 13months), and cyclophosphamide (n=21, OS of 13months). There was no significant difference in toxicities between the C+Bev vs. Bev alone group. CONCLUSION: This retrospective analysis supports that combination chemotherapy and bevacizumab prolongs PFS and OS compared with bevacizumab alone. PMID- 26144602 TI - The application of metal artifact reduction (MAR) in CT scans for radiation oncology by monoenergetic extrapolation with a DECT scanner. AB - Metal artifacts in computed tomography CT images are one of the main problems in radiation oncology as they introduce uncertainties to target and organ at risk delineation as well as dose calculation. This study is devoted to metal artifact reduction (MAR) based on the monoenergetic extrapolation of a dual energy CT (DECT) dataset. In a phantom study the CT artifacts caused by metals with different densities: aluminum (rho Al=2.7 g/cm(3)), titanium (rho Ti=4.5 g/cm(3)), steel (rho steel=7.9 g/cm(3)) and tungsten (rho W=19.3g/cm(3)) have been investigated. Data were collected using a clinical dual source dual energy CT (DECT) scanner (Siemens Sector Healthcare, Forchheim, Germany) with tube voltages of 100 kV and 140 kV(Sn). For each tube voltage the data set in a given volume was reconstructed. Based on these two data sets a voxel by voxel linear combination was performed to obtain the monoenergetic data sets. The results were evaluated regarding the optical properties of the images as well as the CT values (HU) and the dosimetric consequences in computed treatment plans. A data set without metal substitute served as the reference. Also, a head and neck patient with dental fillings (amalgam rho=10 g/cm(3)) was scanned with a single energy CT (SECT) protocol and a DECT protocol. The monoenergetic extrapolation was performed as described above and evaluated in the same way. Visual assessment of all data shows minor reductions of artifacts in the images with aluminum and titanium at a monoenergy of 105 keV. As expected, the higher the densities the more distinctive are the artifacts. For metals with higher densities such as steel or tungsten, no artifact reduction has been achieved. Likewise in the CT values, no improvement by use of the monoenergetic extrapolation can be detected. The dose was evaluated at a point 7 cm behind the isocenter of a static field. Small improvements (around 1%) can be seen with 105 keV. However, the dose uncertainty remains of the order of 10% to 20%. Thus, the improvement is not significant for radiotherapy planning. For amalgam with a density between steel and tungsten, monoenergetic data sets of a patient do not show substantial artifact reduction. The local dose uncertainties around the metal artifact determined for a static field are of the order of 5%. Although dental fillings are smaller than the phantom inserts, metal artifacts could not be reduced effectively. In conclusion, the image based monoenergetic extrapolation method does not provide efficient reduction of the consequences of CT-generated metal artifacts for radiation therapy planning, but the suitability of other MAR methods will be subsequently studied. PMID- 26144601 TI - Assessing the prognostic role of ATR mutation in endometrioid endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study. AB - OBJECTIVE: We sought to validate the clinicopathologic implications and prognostic significance of ATR (ataxia telangiectasia mutated and Rad3-related) mutation in patients with endometrioid endometrial cancer and defective DNA mismatch repair enrolled in a cooperative group molecular staging study of endometrial cancer. METHODS: After pathology review, only endometrioid tumors with high neoplastic cellularity (>=70%) and high quality DNA for molecular analyses were included. MSI (microsatellite instability) typing was performed and the target sequence in exon 10 of ATR was evaluated by direct sequencing in all MSI-high tumors. Associations between ATR mutations and clinicopathologic variables were assessed using contingency table tests. Differences in overall survival (OS) and disease-free survival (DFS) were evaluated by univariate analyses and multivariable Cox proportional hazard models. RESULTS: A total of 475 eligible cases were identified. Of 368 MSI+ cases, the sequence of interest could be successfully genotyped in 357 cases. ATR mutations were exclusively identified in 46 tumors with high level microsatellite instability (MSI+) (12.9%, p<0.001) and were associated with higher tumor grade (p=0.001). ATR mutations were not associated with OS (HR 1.16; 95% CI, 0.58-2.32; p=0.68) or DFS (HR 0.61; 95% CI, 0.25-1.50; p=0.28). CONCLUSION: Truncating mutations in exon 10 of ATR occur exclusively in tumors with evidence of defective DNA mismatch repair. We were not able to confirm the prognostic value of these mutations in patients with endometrioid endometrial cancer. PMID- 26144623 TI - MicroRNAs in tumor angiogenesis. AB - As it is necessary for tumor growth, angiogenesis has been an attractive target for drug therapy. Accumulating evidences indicate that microRNAs (miRNAs), which are short non-coding RNAs, delicately regulate the angiogenic signals through targeting angiogenic factors and protein kinases. They can modulate pro angiogenic signals induced by vascular endothelial growth factor (VEGF) and anti angiogenic signals induced by thrombospondin-1 (TSP-1), and therefore promote or inhibit tumor angiogenesis. Receptor tyrosine kinases (RTKs) and hypoxia inducible factor (HIF) are also targeted by miRNAs. Moreover, miRNAs crosstalk with reactive oxygen species (ROS) influencing tumor angiogenesis. It is critical to understand the role of miRNAs in tumor angiogenesis due to their therapeutic potential to improve outcome for cancer patients. The following review discusses the current state of knowledge related to tumor angiogenesis-regulatory miRNAs and their targets. PMID- 26144624 TI - Neonatal streptozotocin-induced diabetes in mothers promotes metabolic programming of adipose tissue in male rat offspring. AB - AIMS: Maternal hyperglycemia during pregnancy can lead to fetal changes, like macrosomia or obesity in adultlife. Experimentalmodels of diabetes have been studied to evaluate the consequences of offspring lipidmetabolism. This study aimed to investigate the metabolic changes in adipose tissue of offspring of streptozotocininduced diabetic mothers during neonatal period. MAIN METHODS: Diabetes was induced in female rats by streptozotocin administration on 5th day of life. In adulthood, female rats were bred with control male rats. Male puppies were sacrificed on 12th week of life and epididymal (EP) and subcutaneous (SC) adipose fat pads were excised and weighted. Adipocytes were isolated and evaluated for basal and insulin-stimulated 2-deoxyglucose uptake, oxidation of glucose into CO2, and incorporationof glucose into lipids and lipolytic capacity. KEY FINDINGS: Bodyweight, EP fat padweight and diameter of adipocytes fromoffspring of diabeticmothers were increased in comparison to offspring of control mothers. EP adipocytes from offspring of diabetic mothers presented increased basal and insulin stimulated glucose uptake in comparison to control ones. Similar pattern was observed for glucose oxidation into CO2 and incorporation into lipids. However, significant difference in lipolytic capacity in vitrowas not observed. Protein content of GLUT4, insulin receptor and acetyl CoA carboxylase was significantly increased in EP fat pad of offspring of diabetic mothers in relation to control group. SIGNIFICANCE: Metabolic programming occurred in the adipose tissue of offspring of diabetic mothers, increasing its capacity to store lipids with no changes in lipolytic capacity. PMID- 26144637 TI - Features of aggressive breast cancer. AB - BACKGROUND: Aggressive breast cancer is a term commonly used in literature to describe breast cancer with a poor prognosis. Identifying and understanding the factors associated with aggressiveness could be helpful to the management of patients with breast cancer. Breast cancer is a heterogeneous disease, both clinically and biologically, which may be responsible for the wide range of survival durations for patients with metastatic disease. AIM: The goal of this study was to identify the factors most often described in association with aggressive metastatic breast cancer (MBC). METHODS: A systematic review was performed by querying PubMed from January 1, 2012 to June 1, 2014 for "metastatic breast cancer" ("aggressive" or "poor prognosis" or "high risk"). The level of evidence to support each potential prognostic factor of aggressive MBC was also reviewed. RESULTS: The identified factors were grouped into 3 principle categories: clinical, biological, and patient related. Because patient-related factors may not be indicative of inherent cancer aggressiveness, this review focused only on clinical and biological factors. The factors with the highest levels of evidence to support associations with survival in metastatic breast cancer were visceral metastases, number of metastatic sites, disease-free interval, presence of CTCs, triple-negative disease, and tumour grade. CONCLUSION: Identification of these factors and understanding their contribution to the aggressiveness of MBC and disease progression may lead to more personalized treatment in this patient population. PMID- 26144638 TI - Preeclampsia and breast cancer: The influence of birth characteristics. AB - BACKGROUND: In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. METHODS: We conducted a register-based cohort study of all Danish women giving birth during 1978-2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. RESULTS: Compared with women with non preeclamptic pregnancies only, women with one or more preeclamptic pregnancies were 19% significantly less likely to develop breast cancer (IRR = 0.81 [95% CI 0.72-0.93]). We found some indication of greater risk reduction in women with term births, one or more previous births, and in women giving birth to boys. These findings, however, did not reach statistical significance. Finally, risk reduction was slightly greater following milder forms of preeclampsia. CONCLUSION: Our data is compatible with an approximately 20% reduction in risk of developing breast cancer following preeclampsia. Although we find some variability according to birth characteristics, the risk reduction inferred by preeclampsia seems applicable to most preeclamptic pregnancies. PMID- 26144639 TI - Facelift combined with simultaneous fractional laser resurfacing: Outcomes and complications. AB - BACKGROUND: The combination of simultaneous surgical rhytidectomy with ablative resurfacing has been a controversial procedure due to the concern of postoperative wound healing. Traditional ablative resurfacing lasers are believed to have higher rates of complications, leading to delayed healing and skin flap loss when combined with face rhytidectomy surgeries. With the development of fractionated ablative laser therapy, there has been increased interest in combining these two procedures. The objective of this study is to evaluate the clinical outcomes of patients undergoing simultaneous full-face rhytidectomy in combination with fractionated ablative skin resurfacing. METHODS: A retrospective chart analysis was performed for all patients who had a combined procedure of facelift and ablative fractional laser resurfacing from 2008 to 2013 by the senior author (SKS). Postoperative recovery and complications were recorded. The surgical technique used for performing the facelift was an extended supraplatysmal dissection with SMAS plication. Fraxel Re:Pair 10,600-nm fractional carbon dioxide laser was used to perform an ablative resurfacing including the elevated skin flaps. RESULTS: A total of 86 patients were included. Average age was 60.01 years (range of 45-78 years). Longest follow up was five years. The average size of the elevated skin flaps was 100 cm(2). Average skin type was a Fitzpatrick type 2. All patients had complete re-epithelialization by one week after their procedure. Four patients (4.6%) experienced acne outbreaks. Four patients (4.6%) had facial erythema that persisted greater than two weeks. Of these four patients, all resolved by five weeks postoperatively. There was no delayed wound healing or skin flap loss observed. CONCLUSION: Our results indicate that simultaneous rhytidectomy with fractionated ablative laser resurfacing does not cause an increase in wound healing or skin loss. Due to improved patient outcomes with combining these procedures, we believe that this can be increasingly offered as a safe combination. PMID- 26144657 TI - A perspective on genomic-guided anthelmintic discovery and repurposing using Haemonchus contortus. AB - High-throughput molecular and computer technologies have become instrumental for systems biological explorations of parasites. Investigating the genomes and transcriptomes of different developmental stages of parasitic nematodes can provide insights into gene expression, regulation and function in the parasite, which is a significant step toward understanding their biology as well as host interactions and disease. This article covers aspects of a talk given at the MEEGID XII conference in Thailand in 2014. Here, we refer to recent studies of the genomes and transcriptomes of socioeconomically important parasitic nematodes of animals; provide an account of the barber's pole worm (Haemonchus contortus) and emerging drug resistance problems in this and related worms; we also propose a genomic-guided drug discovery and repurposing approach, involving the prediction of the druggable genome, prioritization of drug targets, screening of compound libraries against H. contortus and, briefly, a hit-to-lead optimization approach. We conclude by indicating prospects that molecular tool kits for nematodes provide to the scientific community for future comparative genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological and epidemiological investigations, and as a basis for biotechnological outcomes and translation. PMID- 26144658 TI - Characterization and antibiotic susceptibility of Streptococcus agalactiae isolates causing urinary tract infections. AB - Streptococcus agalactiae (GBS) has been implicated in urinary tract infections but the microbiological characteristics and antimicrobial susceptibility of these strains are poorly investigated. In this study, 87 isolates recovered from urine samples of patients who had attended the Spedali Civili of Brescia (Italy) and had single organism GBS cultured were submitted to antimicrobial susceptibility testing, molecular characterization of macrolide and levofloxacin resistance, PCR based capsular typing and analysis of surface protein genes. By automated broth microdilution method, all isolates were susceptible to penicillin, cefuroxime, cefaclor, and ceftriaxone; 80%, 19.5% and 3.4% of isolates were non-susceptible to tetracycline, erythromycin, and levofloxacin, respectively. Macrolide resistance determinants were iMLS(B) (n=1), cMLS(B) (n=10) and M (n=5), associated with ermTR, ermB and mefA/E. Levofloxacin resistance was linked to mutations in gyrA and parC genes. Predominant capsular types were III, Ia, V, Ib and IX. Type III was associated with tetracycline resistance, while type Ib was associated with levofloxacin resistance. Different capsular type-surface protein gene combinations (serotype V-alp2, 3; serotype III-rib; serotype Ia-epsilon) were detected. A variety of capsular types are involved in significant bacteriuria. The emergence of multidrug resistant GBS may become a significant public health concern and highlights the importance of careful surveillance to prevent the emergence of these virulent GBS. PMID- 26144659 TI - Expression and functionality of Toll- and RIG-like receptors in HepaRG cells. AB - BACKGROUND & AIMS: HepaRG cells are considered as the best surrogate model to primary human hepatocyte (PHH) culture to investigate host-pathogen interactions. Yet their innate immune functions remain unknown. In this study, we explored the expression and functionality of Toll-like (TLR) and retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLR) in these cells. METHODS: Gene and protein expression levels of TLR-1 to 9 and RLR in HepaRG were mainly compared to PHH, by RT-qPCR, FACS, and Western blotting. Their functionality was assessed, by measuring the induction of toll/rig-like themselves and several target innate gene expressions, as well as the secretion of IL-6, IP-10, and type I interferon (IFN), upon agonist stimulation. Their functionality was also shown by measuring the antiviral activity of some TLR/RLR agonists against hepatitis B virus (HBV) infection. RESULTS: The basal gene and protein expression profile of TLR/RLR in HepaRG cells was similar to PHH. Most receptors, except for TLR-7 and 9, were expressed as proteins and functionally active as shown by the induction of some innate genes, as well as by the secretion of IL-6 and IP-10, upon agonist stimulation. The highest levels of IL-6 and IP-10 secretion were obtained by TLR 2 and TLR-3 agonist stimulation respectively. The highest preventive anti-HBV activity was obtained following TLR-2, TLR-4 or RIG-I/MDA-5 stimulations, which correlated with their high capacity to produce both cytokines. CONCLUSIONS: Our results indicate that HepaRG cells express a similar pattern of functional TLR/RLR as compared to PHH, thus qualifying HepaRG cells as a surrogate model to study pathogen interactions within a hepatocyte innate system. PMID- 26144660 TI - Laparoscopic liver resection: A new paradigm in the management of hepatocellular carcinoma? PMID- 26144661 TI - Sit-to-stand biomechanics of individuals with multiple sclerosis. AB - BACKGROUND: It is unclear how people with multiple sclerosis, who often have compromised strength and balance, compare to healthy controls during sit-to-stand movements. The purpose of this study was to compare sit-to-stand biomechanics among three groups: people with multiple sclerosis who exhibit leg weakness, people with multiple sclerosis who have comparable strength to controls, and healthy controls. METHODS: Twenty-one individuals with multiple sclerosis (n=10 exhibiting leg weakness: n=11 exhibiting comparable strength to controls), and 12 controls performed five sit-to-stand trials while kinematic data and ground reaction forces were captured. ANOVAs followed by Tukey's post-hoc tests (alpha=0.05) were used to determine group and limb differences for leg strength, movement time, and sagittal-plane joint kinematics and kinetics. FINDINGS: Persons with multiple sclerosis exhibiting leg weakness displayed decreased leg strength, greater trunk flexion, faster trunk flexion velocity and decreased knee extensor power compared to the other two groups (p<0.05; d>=0.87), and slower rise times compared to controls(p<0.03; d>=1.17). No differences were found between controls and the multiple sclerosis-comparable strength group. Across all 3 groups, leg strength was moderately correlated with trunk kinematics and knee extensor velocities, moments and powers of the sit-to-stand (p<=0.05). INTERPRETATION: Participants with multiple sclerosis exhibiting leg weakness took longer to stand and appeared to use a trunk-flexion movement strategy when performing the sit-to-stand. The majority of group differences appear to be a result of leg extension weakness. Treatment that includes leg strengthening may be necessary to improve sit-to-stand performance for people with multiple sclerosis. PMID- 26144662 TI - Can two-dimensional video analysis during single-leg drop vertical jumps help identify non-contact knee injury risk? A one-year prospective study. AB - BACKGROUND: Previous studies showed that the amount of hip flexion and the combination of knee valgus and lateral trunk motion, measured with two dimensional video analysis, were related to three-dimensional measured knee joint moments during single-leg drop vertical jumps, but it remains unclear whether these measurements can be used to identify non-contact knee injury risk. METHODS: Fifty injury-free female athletes participated in the study. Two-dimensional video analysis was used to measure hip flexion, knee valgus and lateral trunk motion angles during single-leg drop vertical jumps. Time loss non-contact knee injuries were registered during a one-year follow-up. Independent t-tests and receiver operating characteristic analysis were used to analyze the predictive ability of the two-dimensional angles. FINDINGS: Seven participants sustained a time loss non-contact knee injury. Hip flexion was not significantly different between groups (P>.05). The combination of knee valgus and lateral trunk motion was significantly smaller in the injured (P=.036) and non-injured legs (P=.009) of the future injured group compared with the respective matched leg of the non injured group. The receiver operating characteristic analysis showed a significant discriminative accuracy between groups for the combination of knee valgus and lateral trunk motion of the uninjured leg of the future injured group with the matched leg of the non-injured group (area under curve=0.803; P=.012). INTERPRETATION: The measurement of a combination of increased knee valgus and ipsilateral trunk motion during the single-leg drop vertical jump with two dimensional video analysis can be used to help identify female athletes with increased non-contact knee injury risk. PMID- 26144663 TI - Real-time feedback during drop landing training improves subsequent frontal and sagittal plane knee kinematics. AB - BACKGROUND: Although neuromuscular training featuring visual feedback may benefit modification of anterior cruciate ligament injury-risk linked knee kinematics, wide-spread clinical intervention has been limited to date. This study evaluated the effects of a Microsoft Kinect-based feedback system for modification of drop vertical jump knee kinematics traditionally consistent with predisposition to non contact anterior cruciate ligament injury in female athletes. We hypothesized that a four-week feedback training protocol would increase peak knee flexion angle and frontal plane valgus-correlated knee separation distance during drop jump landing performance. METHODS: Twenty-four female athletes were randomly divided equally into control or Kinect-based feedback groups. Subjects were pre screened for peak knee flexion angle and minimum knee separation distance during drop landing and later performed twenty 31cm drop landings three days per week for four weeks. The feedback group received Kinect-based visual feedback, while controls did not. Kinematics were re-assessed immediately following the end of the training period. FINDINGS: The feedback group increased peak knee flexion and experienced a greater improvement in peak knee flexion. The feedback group improved normalized knee separation distance with greater improvement in post training peak knee separation distance as compared with controls. INTERPRETATION: Kinect-based feedback training significantly improved drop vertical jump knee kinematics associated with non-contact anterior cruciate ligament injury. The Kinect-based feedback approach demonstrates promise for mitigating non-contact anterior cruciate ligament injury predisposing knee biomechanics in female athletes within the clinical environment. PMID- 26144664 TI - Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route. AB - Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations. PMID- 26144665 TI - Investigation of the stabilizer elimination during the washing step of charged PLGA microparticles utilizing a novel HPLC-UV-ELSD method. AB - Quantification of stabilizer content in microparticles and other products is of great importance for formulation development, drug product quality control as well as for reproducible manufacturing. A fast and sensitive HPLC method with evaporative light scattering detection (ELSD) capable of detecting docusate sodium (DOSS), poly (lactic-co-glycolic acid) (PLGA; Resomer RG 503 H) and R-1,2 dioleoyloxy-3-trimethylammonium-propane (DOTAP) in a single run was successfully developed. In contrast to previously described methods, hydrolysis of PLGA as pretreatment is not necessary, thereby enabling accurate quantification of stabilizer next to the intact matrix polymer. This method was used to investigate the impact of washing procedures of polymeric microparticles manufactured either with anionic stabilizer DOSS or with cationic stabilizer DOTAP. High amounts of DOSS were detected in the washing water. This finding was consistent with the result that no DOSS could be detected in the washed and dried microparticles (=3 months) volunteered in the study. An experienced musculoskeletal physiotherapist evaluated and classified participants into either SIJ-positive [n(45)] or SIJ-negative [n(77)] group, using the reference standard pain provocation tests [>=3 positive tests = SIJ-positive]. A research physiotherapist, blinded to clinical groups, conducted the innominate kinematic testing using a valid and reliable electromagnetic palpation digitization technique, during prone lying incremental hip abduction-external rotation test positions. RESULTS: The results of the mixed model regression analyses demonstrated that SIJ-positive participants exhibited significantly different innominate movement patterns and trends of rotation, but not innominate ranges of motion, when compared with SIJ-negative LBP participants. CONCLUSIONS: These findings demonstrate association between SIJ pain and altered innominate kinematics, and have led the groundwork for further exploration of clinical measurement, relevance, and management of these potentially important movement observations. PMID- 26144667 TI - Psychophysical testing in rodent models of glaucomatous optic neuropathy. AB - Processing of visual information begins in the retina, with photoreceptors converting light stimuli into neural signals. Ultimately, signals are transmitted to the brain through signaling networks formed by interneurons, namely bipolar, horizontal and amacrine cells providing input to retinal ganglion cells (RGCs), which form the optic nerve with their axons. As part of the chronic nature of glaucomatous optic neuropathy, the increasing and irreversible damage and ultimately loss of neurons, RGCs in particular, occurs following progressive damage to the optic nerve head (ONH), eventually resulting in visual impairment and visual field loss. There are two behavioral assays that are typically used to assess visual deficits in glaucoma rodent models, the visual water task and the optokinetic drum. The visual water task can assess an animal's ability to distinguish grating patterns that are associated with an escape from water. The optokinetic drum relies on the optomotor response, a reflex turning of the head and neck in the direction of the visual stimuli, which usually consists of rotating black and white gratings. This reflex is a physiological response critical for keeping the image stable on the retina. Driven initially by the neuronal input from direction-selective RGCs, this reflex is comprised of a number of critical sensory and motor elements. In the presence of repeatable and defined stimuli, this reflex is extremely well suited to analyze subtle changes in the circuitry and performance of retinal neurons. Increasing the cycles of these alternating gratings per degree, or gradually reducing the contrast of the visual stimuli, threshold levels can be determined at which the animal is no longer tracking the stimuli, and thereby visual function of the animal can be determined non-invasively. Integrating these assays into an array of outcome measures that determine multiple aspects of visual function is a central goal in vision research and can be realized, for example, by the combination of measuring optomotor reflex function with electroretinograms (ERGs) and optical coherence tomography (OCT) of the retina. These structure-function correlations in vivo are urgently needed to identify disease mechanisms as potential new targets for drug development. Such a combination of the experimental assessment of the optokinetic reflex (OKR) or optomotor response (OMR) with other measures of retinal structure and function is especially valuable for research on GON. The chronic progression of the disease is characterized by a gradual decrease in function accompanied by a concomitant increase in structural damage to the retina, therefore the assessment of subtle changes is key to determining the success of novel intervention strategies. PMID- 26144686 TI - Prediction of outcome in patients with low back pain--A prospective cohort study comparing clinicians' predictions with those of the Start Back Tool. AB - The clinical course of low back pain (LBP) cannot be accurately predicted by existing prediction tools. Therefore clinicians rely largely on their experience and clinical judgement. The objectives of this study were to investigate 1) which patient characteristics were associated with chiropractors' expectations of outcome from a LBP episode, 2) if clinicians' expectations related to outcome, 3) how accurate clinical predictions were as compared to those of the STarT Back Screening Tool (SBT), and 4) if accuracy was improved by combining clinicians' expectations and the SBT. Outcomes were measured as LBP intensity (0-10) and disability (RMDQ) after 2-weeks, 3-months, and 12-months. The course of LBP in 859 patients was predicted to be short (54%), prolonged (36%), or chronic (7%). Clinicians' expectations were most strongly associated with education, LBP history, radiating pain, and neurological signs at baseline and related to all outcomes. The accuracies of predictions made by clinicians (AUC .58-.63) and the SBT (AUC .50-.61) were comparable and low. No substantial increase in the predictive capability was achieved by combining clinicians' expectations and the SBT. In conclusion, chiropractors' predictions were associated with well established prognostic factors but not simply a product of these. Chiropractors were able to predict differences in outcome on a group level, but prediction of individual patients' outcomes were inaccurate and not substantially improved by the SBT. It is worth investigating if more accurate tools can be developed to assist clinicians in prediction of outcome. PMID- 26144696 TI - Gastroprotective activity of the hydroethanolic extract and isolated compounds from the leaves of Solanum cernuum Vell. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Solanum cernuum Vell. (Solanaceae) is a Brazilian medicinal plant, traditionally known as "panaceia". Its folk name is probably due to its wide range of applications in traditional medicine including the treatment of ulcers. AIM OF THE STUDY: To evaluate the gastroprotective activities of the hydroethanolic extract (ESC) of S. cernuum and its major isolated compounds using in vivo gastric ulcer models. MATERIAL AND METHODS: The ESC extract was obtained by maceration followed by percolation of the dried and powdered leaves of S. cernuum in ethanol:water (7:3). The major compounds in the extract were isolated by applying various preparative chromatographic techniques. The gastroprotective activity was evaluated in mice using different gastric ulcer-induced models. The anti-Helicobacter pylori activity was performed using the agar-well diffusion and broth microdilution methods. RESULTS: The ESC extract showed gastroprotective effects in the assay of acute gastric ulcer-induced by HCl/EtOH, nonsteroidal anti-inflammatory drug, and acetic acid-induced chronic ulcer protocols. The results also demonstrated that the gastroprotection induced by ESC extract is related to the activity of nitric oxide and endogenous sulfhydryls, which are important gastroprotective factors. The ESC extract and the alkaloid cernumidine did not show activity against H. pylori in the concentrations tested. CONCLUSIONS: The present study showed that the crude extract of S. cernuum possessed gastroprotective activity which corroborating the traditional use of this plant for the treatment of gastric ulcers. The isolated flavonoids, quercitrin and afzelin as well as the phenylpropanoid, isoferulic acid are suggested to be the compounds responsible for the gastroprotective activity of S. cernuum extract. PMID- 26144697 TI - Hepatoprotective effects of Yulangsan polysaccharide against nimesulide-induced liver injury in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Yulangsan polysaccharide (YLSPS) is often used in popular folk medicine in the Guangxi Zhuang Autonomous Region of China as a chief ingredient of Millettia pulchra, which is used as a hepatic protection, anti aging and memory improving agent. AIM OF THE STUDY: This study was designed to investigate the protective effects of polysaccharides from Millettia pulchra Kurz var.laxior (Dunn) (Yulangsan polysaecharide, YLSPS) against nimesulide-induced hepatotoxicities in mice. MATERIALS AND METHODS: Liver injury was induced in mice by administering nimesulide. Simultaneously, YLSPS was administered 2h prior to the administration of nimesulide. Dimethyl diphenyl bicarboxylate (DDB) was used as a reference drug. RESULTS: Compared with the nimesulide group, YLSPS significantly decreased the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and the content of bilirubin in the serum. The anti-oxidative effect of YLSPS was observed from the increase of the superoxide dismutase (SOD) and catalase and glutathione peroxidase (GSH-Px) activities in the liver, both of which were decreased by nimesulide. Moreover, the content of malondialdehyde (MDA) was reduced, and histological findings also confirmed the anti-hepatotoxic activity. In addition, YLSPS significantly inhibited proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). Additionally, YLSPS also enhanced the mitochondrial antioxidant and inhibited dead cells by preventing the down-regulation of Bcl-2, up-regulation and release of Bax along with caspase 9 and 3 activity, confirming the involvement of mitochondria in the nimesulide induced apoptosis. CONCLUSION: The protective effect of YLSPS against nimesulide induced hepatic injury may rely on its ability to reduce oxidative stress and prevent nimesulide-induced hepatotoxicity by inhibiting critical control points of apoptosis. PMID- 26144698 TI - Accumulation of (131)INa activity in renal cysts unrelated to metastatic disease in a patient with differentiated thyroid cancer. PMID- 26144699 TI - (131)I treatment in Differentiated Thyroid Cancer and End-Stage Renal Disease. AB - PURPOSE: Radioiodine (RAI) is a cornerstone in the treatment of Differentiated Thyroid Cancer (DTC). In patients on haemodialysis due to End-Stage Renal Disease (ESRD), it must be used cautiously, considering the renal clearance of this radionuclide. Also, the safety of the procedure and subsequent long-term outcome is still not well defined. In 2001, we described a dosimetric method and short term results in three patients, with a good safety profile. We hypothesize that our method is safe in a long-term scenario without compromising the prognosis of both renal and thyroid disease. MATERIAL AND METHODS: Descriptive-retrospective study. A systematic search was carried out using our clinical database from 2000 to 2014. INCLUSION CRITERIA: DTC and radioiodine treatment while on haemodialysis. EXCLUSION CRITERIA: peritoneal dialysis. RESULTS: Final sample n=9 patients (n=5 males), age 48 years (median age 51 years males, 67 years female group); n=8 papillary thyroid cancer, n=1 follicular thyroid cancer; n=5 lymph node invasion; n=1 metastatic disease. Median RAI dose administered on haemodialysis 100mCi. 7.5 years after radioiodine treatment on haemodialysis, n=7 deemed free of thyroid disease, n=1 persistent non-localised disease. No complications related to the procedure or other target organs were registered. After 3.25 years, n=4 patients underwent successful renal transplantation; n=4 patients did not meet transplantation criteria due to other conditions unrelated to the thyroid disease or its treatment. One patient died due to ischemic cardiomyopathy (free of thyroid disease). CONCLUSIONS: Radioiodine treatment during haemodialysis is a long-term, safe procedure without worsening prognosis of either renal or thyroid disease. PMID- 26144701 TI - Factors Influencing the Treatment Response of Pigment Epithelium Detachment in Age-Related Macular Degeneration. AB - PURPOSE: To study the effect of various baseline factors, particularly the type of drug (ranibizumab vs aflibercept), on the functional and anatomic response of treatment-naive pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (neovascular AMD), after 3 intravitreal injections. DESIGN: Retrospective consecutive case series. METHODS: This study included 102 patients (n = 115 eyes) with treatment-naive neovascular AMD and PED (>150 MUm), who were treated with either ranibizumab (n = 68 eyes) or aflibercept (n = 47 eyes). A multivariate analysis using stepwise linear regression was performed in order to assess factors influencing visual acuity improvement, as well as treatment response of PED height after 3 monthly injections. RESULTS: Multivariate analysis revealed that better visual improvement was associated with lower best-corrected visual acuity (BCVA) at baseline (P = .001), presence of subretinal fluid (P = .001), and retinal angiomatous proliferation (P = .001); PED reduction was associated with higher PED at baseline (P = .001), predominantly serous PED (P = .003), and the use of aflibercept (P = .022). Drug type was not associated with change in BCVA at 3 months. CONCLUSION: Eyes with neovascular AMD and PED showed significant functional and anatomic response after 3 monthly intravitreal anti-VEGF injections. The functional response depended on baseline BCVA, presence of subretinal fluid, and retinal angiomatous proliferation, while anatomic response was influenced by baseline PED height, degree of vascularization, and drug type. Drug type was not associated with change in BCVA, but had a weak effect on anatomic response. PMID- 26144700 TI - Relationship Between Juxtapapillary Choroidal Volume and Beta-Zone Parapapillary Atrophy in Eyes With and Without Primary Open-Angle Glaucoma. AB - PURPOSE: To evaluate whether quantity of choroidal tissue directly adjacent to the optic nerve differs between eyes with and without glaucoma and whether beta zone parapapillary atrophy influences this relationship. DESIGN: Prospective cohort study. METHODS: Subjects were enrolled in a longitudinal, observational study at our institution. We studied 1 eye of 63 primary open-angle glaucoma (POAG), 30 ocular hypertension (OH), and 48 control subjects. Using optical coherence tomography enhanced depth imaging, we acquired 12 radial scans centered on the optic nerve head with 15 degrees of separation between scans. After images were enhanced, segmented, and corrected for ocular magnification, juxtapapillary choroidal volumetric parameters were calculated using raw thickness measurements and standard interpolation techniques. Juxtapapillary choroidal volume was then compared by diagnosis and by beta-zone parapapillary atrophy status. RESULTS: Total juxtapapillary choroidal volume was significantly reduced in POAG vs OH and control eyes (1.057 vs 1.228 vs 1.255 MUL, P = .04) and it was reduced in eyes with vs without beta-zone parapapillary atrophy (1.076 MUL, n = 80 vs 1.306 MUL, n = 61, P < .001). Juxtapapillary choroidal volume did not differ between POAG, OH, and control eyes when beta-zone parapapillary atrophy was absent, but juxtapapillary choroidal volume was significantly reduced in POAG vs control eyes when beta-zone parapapillary atrophy was present (0.957 vs 1.196 MUL, P = .02). Furthermore, POAG eyes with beta-zone parapapillary atrophy had substantially lower juxtapapillary choroidal volume compared to POAG eyes without beta-zone parapapillary atrophy (0.957 vs 1.356 MUL, P < .001). CONCLUSIONS: The volume of choroid adjacent to the optic nerve was significantly reduced in POAG eyes when beta-zone parapapillary atrophy was present, suggesting that beta-zone parapapillary atrophy may be a biomarker for juxtapapillary choroidal atrophy and associated vascular compromise in POAG. PMID- 26144740 TI - Task-switching preparation across semantic and spatial domains: An event-related potential study. AB - Previous event-related potential (ERP) studies have identified the specific electrophysiological markers of advance preparation in cued task-switching paradigms. However, it is not yet completely clear whether there is a single task independent preparatory mechanism for task-switching or whether preparation for a switch can be selectively influenced by the domain of the task to be performed. To address this question, we employed a cued-task switching paradigm requiring participants to repeat or to switch between a semantic and a spatial task. The behavioural results showed a significant switch cost for both domains. The ERP findings, however, revealed that switch and repeat trials for semantic and spatial domains differed in the amplitude modulation of an early P2 and a sustained negativity both expressed over fronto-central scalp regions. Further differences between the two domains also emerged over posterior-parietal electrodes. This pattern of data thus shows that advance preparation in task switching can be selectively modulated by the domain of the task to be performed. PMID- 26144754 TI - Hepatitis C risk factors, attitudes and knowledge among HIV-positive, HIV negative and HIV-untested gay and bisexual men in Australia. AB - Background There are increasing reports of sexual transmission of hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM). Still unclear is the level of HCV knowledge and the risk factors specific to HCV transmission among this population. This study compared HCV knowledge and risk practices among HIV-positive, HIV-negative and HIV-untested gay and bisexual men in Australia. METHODS: Participants (n=534) completed an online survey assessing sexual risk practices, HCV knowledge, perceived risk of acquiring HCV and perceptions of people with HCV and who inject drugs. RESULTS: HIV-positive participants were older, reported greater engagement in sexual risk and injecting drug practices, felt they were at greater risk of acquiring HCV, were less likely to socially and sexually exclude people with HCV and had more positive attitudes towards people who inject drugs and people with HCV compared with HIV-negative and HIV-untested participants. HIV-untested participants were younger, reported fewer HCV-related serosorting practices and were more likely to socially and sexually exclude people with HCV than the other groups. CONCLUSIONS: Findings suggest that HCV education and prevention for gay men may be most effective if tailored according to HIV status. For HIV-positive men, health promotion could focus on specific sexual practices and biological factors linked to HCV transmission, regular HCV testing and better strategies for disclosure of HCV serostatus. For HIV-negative and HIV-untested men, there should be a more general focus on awareness, changing attitudes towards HCV testing and increasing general knowledge around HCV, including evidence of sexual transmission. PMID- 26144818 TI - The dynamics of adsorption and dissociation of N2 in a monolayer of iron on W(110). AB - We study the adsorption dynamics of N2 on an expanded monolayer of Fe grown pseudomorphically on W(110). To this aim we have performed molecular dynamics simulations in a six-dimensional potential energy surface calculated within density functional theory. Our results show that N2 dissociation on this surface is a highly activated process with an energy barrier of around 1.25 eV. Regarding molecular adsorption, we find that the energetically most favorable adsorption well corresponds to a parallel orientation of the molecule with an adsorption energy of around 520 meV. However, at low molecular energies and surface temperatures, the molecules preferentially adsorb vertically to the surface with an adsorption energy of around 480 meV. A comparative analysis with the results previously obtained on a clean Fe(110) surface shows that while surface strain favors molecular adsorption of N2 in this system, it impedes dissociative adsorption. The former is consistent with the experimental observations showing that the inertness of Fe(110) towards N2 uptake is reduced in the strained surface. The latter leads us to suggest that the experimental observation of dissociated atomic N in the strained surface when increasing surface temperature must be related to the presence of step/defects at the surface. PMID- 26144817 TI - Cardiolipin fingerprinting of leukocytes by MALDI-TOF/MS as a screening tool for Barth syndrome. AB - Barth syndrome (BTHS), an X-linked disease associated with cardioskeletal myopathy, neutropenia, and organic aciduria, is characterized by abnormalities of card-iolipin (CL) species in mitochondria. Diagnosis of the disease is often compromised by lack of rapid and widely available diagnostic laboratory tests. The present study describes a new method for BTHS screening based on MALDI-TOF/MS analysis of leukocyte lipids. This generates a "CL fingerprint" and allows quick and simple assay of the relative levels of CL and monolysocardiolipin species in leukocyte total lipid profiles. To validate the method, we used vector algebra to analyze the difference in lipid composition between controls (24 healthy donors) and patients (8 boys affected by BTHS) in the high-mass phospholipid range. The method of lipid analysis described represents an important additional tool for the diagnosis of BTHS and potentially enables therapeutic monitoring of drug targets, which have been shown to ameliorate abnormal CL profiles in cells. PMID- 26144819 TI - [Management of mentally handicapped patients: room for improvement!]. PMID- 26144820 TI - [Collaboration between nurses and nurse-assistants]. PMID- 26144821 TI - ["Working together" at hospital?]. AB - Working well together at hospital depends on several factors, on the level of a team as well as that of the ministry in charge of health. How can we encourage and promote cooperation between caregivers? If the hospital is the reflection of society as a whole, an analysis of the functioning of this universe provides a better understanding of the challenges and the missions of each player for the benefit of the patient. PMID- 26144822 TI - [Involvement of healthcare assistants in nursing procedures]. AB - Healthcare assistants are authorised to perform nursing procedures in accordance with regulated conditions. They do not perform their functions autonomously but carry out their actions within the framework of the nurse's responsibilities. PMID- 26144823 TI - [The nurse-healthcare assistant partnership: a learning tool?]. AB - In intensive care, working in a nurse-healthcare assistant partnership is essential. It facilitates the way they receive the patient, organise and work together in performing technical procedures, provide personal care and comfort and compensate for a decrease in or loss of autonomy. PMID- 26144824 TI - [A partnership for the benefit of patients in geriatrics]. AB - In geriatrics, with the longer life expectancy and the growing number of neurodegenerative diseases, the need for care is increasing and working together is fundamental. The nurse/healthcare assistant partnership is the guarantor of improving patients' quality of care. PMID- 26144825 TI - [The nurse-healthcare assistant partnership in a mobile pain and palliative care team]. AB - The mission of the mobile pain and palliative care team is to improve the quality of care and comfort of patients. At Longjumeau general hospital the nurse healthcare assistant partnership within this team enables the patient to benefit from the caregivers' two-way perspective, while allowing the professionals to share knowledge and to be stronger in the face of suffering. PMID- 26144826 TI - [The approach to care in oncology]. AB - This young graduate nurse has opted for the demanding but rewarding work within a cancer unit. Attached to a research and teaching centre, her unit provides care from multidisciplinary and international teams. Beyond the technical aspects, the patient and their families are at the centre of the health professionals' focus. PMID- 26144827 TI - [Burnout is not a fatality]. AB - How can the infernal spiral which leads to burnout be identified? What are the reflexes to adopt in order to protect against it? This article provides the keys to understanding and preventing burnout, in order to develop, instead, a real supply of wellbeing at work. PMID- 26144828 TI - [The role of care assistants at the end of life]. AB - Personal care assistants have a special place, at home, with patients at the end of their life. At the interface between carers, relatives and the person they take care of, they often live intense situations, in close contact. The Parisian palliative care network Quietude shares their voice. PMID- 26144829 TI - [A tool for helping psychiatric patients regain their autonomy]. AB - The "Hygiene de vie" ("personal health practices") group is a nursing initiative and innovative tool helping patients to regain their autonomy and facilitating their resocialisation as close as possible to their living environment. An approach centred on the links with network partners is essential, as the team of the adult day care center in Vaulx-en-Velin testifies. PMID- 26144830 TI - [Telephone and coordination of intensive care in hospital]. AB - The telephone is a central tool for the coordination of care in hospitals between the general wards and intensive care. Calls are short and frequent. They concern a wide variety of issues handled in parallel with other activities. This research, carried out by a Swiss team, examines the practices of telephone communication in hospitals. PMID- 26144832 TI - [The nurse and ulcer treatments]. PMID- 26144831 TI - [Treating accident or chemical attack casualties in hospital]. AB - It is mandatory for all hospitals to be prepared for the occurrence of a chemical biological, radiological or nuclear (CBRN) event. This preparation requires specific investment on the part of the hospital management, as well as from the nursing teams on the frontline. Teams from Lariboisiere hospital in Paris have been working on these risks for several years. PMID- 26144833 TI - Advice for a Colostomy Patient. PMID- 26144834 TI - [Introduction to diagnostic imaging]. PMID- 26144835 TI - [Standardized patient care plan for post-operative care units]. PMID- 26144836 TI - [Continuity of care for patients after postoperative recovery room stay]. PMID- 26144837 TI - The graphene/nucleic acid nanobiointerface. AB - The combination of nanomaterials with biomolecules yields functional nanostructured biointerfaces with synergistic properties and functions. Owing to a unique combination of its crystallographic and electronic structure, graphene and its derivatives exhibit several superior and typical properties, and has emerged as an attractive candidate for the fabrication of novel nanobiointerfaces with different kinds of unique applications. As is known, nucleic acids are stable and can easily handle modification, and can recognize a wide range of targets with high selectivity, specificity, and affinity. The integration of nucleic acids with graphene-based materials has been substantially advanced over the past few years, achieving amazing properties and functions, thereby exhibiting attractive potential applications in biosensing, diagnostics, drug screening and biomedicine. Herein, this review addresses the recent progress on the design and fabrication of graphene/nucleic acid nanostructured biointerfaces, and the fundamental understanding of their interfacial properties, as well as the various nanobiotechnological applications. To begin with, we summarize the basic features of the graphene and nucleic acid-based nanobiointerface, especially the interfacial interaction mechanism and the resulting biological effects. Then, the fabrication and characterization methodology of graphene and nucleic acid-based nanobiointerfaces are discussed. Next, particular emphasis is directed towards the exploration of their biosensing and biomedical applications, including small molecule detection, protein and DNA sensing/sequencing, as well as gene delivery and therapy. Finally, some significant prospects, further opportunities and challenges in this emerging field are also suggested. PMID- 26144838 TI - Drug-loaded pseudo-block copolymer micelles with a multi-armed star polymer as the micellar exterior. AB - Supramolecular constructed pseudo block copolymer micelles based on beta cyclodextrin terminated 4 and 7 armed star poly(N-vinylpyrrolidone) and adamantane terminated linear poly(epsilon-caprolactone) were prepared. The size, morphology, stability and protein adsorption were experimentally examined. The micelles with 7 armed PVP chains as the micellar exterior showed the lowest amount of protein adsorption and the best stability in media. When cabazitaxel, a new taxane, was loaded into the micelles, 14.4% drug loading content and 85% encapsulation efficacy were achieved. In vitro cytotoxicity studies demonstrated that the cabazitaxel-loaded micelles show significant cytotoxicity against drug resistant A2780/T cell lines. Biodistribution studies showed that the micelles can almost double the content of cargo in tumor sites compared with the free cargo. In vivo antitumor activity examinations indicated that cabazitaxel-loaded micelles show superior antitumor activity over free paclitaxel and free cabazitaxel. PMID- 26144839 TI - Optically binary liquid crystalline blue phases induced by one-armed cholesterol linked azobenzene molecules. AB - A series of one-armed cholesterol-linked azobenzene molecules named CholXAzo with different spacers were synthesized, in which Chol6Azo was found to have induced blue phases (BPs) with a concentration of 4.0 wt%. Under irradiation of 385 nm UV light with a density of 15.0 mW cm(-2), photo-responsive behaviour of the 4.0 wt% Chol6Azo doped sample named B3 shows a sensitive temperature dependence, which means that at 38.0 degrees C a phase transition from BPs to the isotropic phase is induced; however, at 33.0 degrees C, this phase transition does not take place. Results from the research show that the optically binary phase transition behaviour of B3 is sensitive to the isomerization degree of Chol6Azo, which is closely related to the stability of the BP structure and there is a critical isomerization degree of 13.7% for the phase transition of the B3 liquid crystals. Further POM observation shows that the liquid crystal samples doped with different concentrations of Chol6Azo have an increasing transition temperature for photo-induced phase transition from the BP to the isotropic phase along with the increasing concentration of Chol6Azo, which are found to have the same changing tendency with phase transition temperature from the isotropic phase to BPs and a phase diagram is made to map the optically binary behaviour of Chol6Azo doped blue phase liquid crystals. At last, a simple pattern with the BP and the isotropic phase arranged at an interval was made in this optically binary liquid crystalline blue phase under a suitable photomask. PMID- 26144841 TI - Aryl-BIAN-ligated silver(I) trifluoromethoxide complex. AB - A reaction of acetonitrile-solvated AgOCF3 with 1 equiv. of Aryl-BIAN ligand in THF at room-temperature afforded the silver(i) complex (Aryl-BIAN)AgOCF3 (1) in 75% yield. The crystal structure of this silver(i) trifluoromethoxide was determined by single-crystal X-ray crystallography. The molecular structure of 1 shows the metal centre bound to one molecule of BIAN, one trifluoromethoxide and one THF solvate, resulting in a distorted tetrahedral silver. Density functional theory (DFT) calculations and the natural bond orbital (NBO) analysis were conducted to give insights into the electronic structure of 1 and the bonding characters of the OCF3 group. The reactivity of 1 towards trifluoromethoxylation of organic halides was also examined; a reaction with benzyl bromides gave the desired products of benzyl trifluoromethyl ethers in good to excellent yields. PMID- 26144840 TI - Special Enrichment Strategies Greatly Increase the Efficiency of Missing Proteins Identification from Regular Proteome Samples. AB - As part of the Chromosome-Centric Human Proteome Project (C-HPP) mission, laboratories all over the world have tried to map the entire missing proteins (MPs) since 2012. On the basis of the first and second Chinese Chromosome Proteome Database (CCPD 1.0 and 2.0) studies, we developed systematic enrichment strategies to identify MPs that fell into four classes: (1) low molecular weight (LMW) proteins, (2) membrane proteins, (3) proteins that contained various post translational modifications (PTMs), and (4) nucleic acid-associated proteins. Of 8845 proteins identified in 7 data sets, 79 proteins were classified as MPs. Among data sets derived from different enrichment strategies, data sets for LMW and PTM yielded the most novel MPs. In addition, we found that some MPs were identified in multiple-data sets, which implied that tandem enrichments methods might improve the ability to identify MPs. Moreover, low expression at the transcription level was the major cause of the "missing" of these MPs; however, MPs with higher expression level also evaded identification, most likely due to other characteristics such as LMW, high hydrophobicity and PTM. By combining a stringent manual check of the MS2 spectra with peptides synthesis verification, we confirmed 30 MPs (neXtProt PE2 ~ PE4) and 6 potential MPs (neXtProt PE5) with authentic MS evidence. By integrating our large-scale data sets of CCPD 2.0, the number of identified proteins has increased considerably beyond simulation saturation. Here, we show that special enrichment strategies can break through the data saturation bottleneck, which could increase the efficiency of MP identification in future C-HPP studies. All 7 data sets have been uploaded to ProteomeXchange with the identifier PXD002255. PMID- 26144842 TI - New insights into the kinetic target-guided synthesis of protein ligands. AB - The kinetic target-guided synthesis (KTGS) strategy is an unconventional discovery approach that takes advantage of the presence of the biological target itself in order to irreversibly assemble the best inhibitors from an array of building blocks. This strategy has grown over the last two decades notably after the introduction of the in situ click chemistry concept by Sharpless and colleagues in the early 2000s based on the use of the Huisgen cycloaddition between terminal alkynes and azides. KTGS is a captivating area of research offering an unprecedented and powerful strategy to probe the macromolecular complexity and dynamics of biological targets. After a brief introduction listing all chemical ligation reactions reported to date in KTGS, this review focuses on the last five years' progress to expand the repertoire of the click or "click like" tool box targeting proteins, as well as to overcome limitations arising in particular from false negatives, i.e. potent ligands that are not formed, or formed in undetectable trace amounts. Furthermore, we wish to analyze the new twists and novelties described in some of these applications in order to better understand the conditions that govern this strategy and the extent to which it can be developed and generalized for a more efficient process. PMID- 26144843 TI - Acute toxicity of robotic ultrahypofractionated radiotherapy CyberKnifeTM in prostate cancer patients. AB - Our purpose was to evaluate the toxicity of CyberKnifeTM based fractionated stereotactic radiotherapy (FSRT) in prostate cancer patients. One-hunred-thirty two men with low (62) and intermediate (70) prostate cancer were enrolled in our prospective study. Mean age was 69. Total dose of 36,25 Gy in 5 fractions was prescribed. Image guided FSRT was performed on CyberKnife. Minimum follow-up ranged from 3 to 28 months. EORTC/RTOG scale was used to evaluate toxicity. A total of 47%, 10% and 2% of patients presented grade 1, 2 and 3 acute genitourinary toxicity, respectively. In 25% and 3% of patients, respectively, grade 1 and 2 acute gastrointestinal toxicity was observed. No significant association between acute grade >= 2 toxicity and clinical factors: age, androgen deprivation therapy or infections were found. Neither CTV nor PTV volumes had significant impact on acute grade >= 2 toxicity. Late toxicity was assessed in 104 patients. In 16% and 1% of patients late GU toxicity in grade 1 and 2, respectively, was presented. Late GI toxicity grade 1, 2 and 3 occurred in 8%, 3% and 1% of patients, respectively. The acute toxicity rates of fractionated stereotactic radiotherapy are low. Early data suggest also low late toxicity rates. PMID- 26144844 TI - Hybrid materials of Ni NP@MOF prepared by a simple synthetic method. AB - We demonstrate a novel, simple synthetic method for metal (Ni) NPs in a MOF using the partial thermal decomposition of nickel(II) 2,5-dihydroxyterephthalate (Ni MOF-74). The Ni NPs inside the Ni-MOF-74 are several nanometers in size, and the size can be precisely controlled by the heating conditions. PMID- 26144845 TI - Quantum interference and structure-dependent orbital-filling effects on the thermoelectric properties of quantum dot molecules. AB - The quantum interference and orbital filling effects on the thermoelectric (TE) properties of quantum dot (QD) molecules with high figure of merit are illustrated via the full solution to the Hubbard-Anderson model in the Coulomb blockade regime. It is found that under certain conditions in the triangular QD molecule (TQDM), destructive quantum interference (QI) can occur, which leads to vanishingly small electrical conductance, while the Seebeck coefficient is modified dramatically. When the TQDM is in the charge localization state due to QI, the Seebeck coefficient is seriously suppressed at low temperature, but is highly enhanced at high temperature. Meanwhile, the behavior of the Lorenz number reveals that it is easier to block charge transport via destructive QI than the electron heat transport at high temperatures. The maximum power factor (PF) in the TQDM occurs under full-filling conditions. Nevertheless, low-filling conditions are preferred for getting the maximum PF in serially coupled triple QDs in general. In double QDs, the maximum PF can be achieved either with orbital depletion or orbital-filling as a result of electron-hole symmetry. Our theoretical work provides a useful guideline for the advancement of the nanoscale TE technology. PMID- 26144846 TI - Correction: Surface- and tip-enhanced Raman scattering of bradykinin onto the colloidal suspended Ag surface. PMID- 26144847 TI - A facile method for fabrication of buckled PDMS silver nanorod arrays as active 3D SERS cages for bacterial sensing. AB - Our results demonstrate that it is possible, by means of generation of buckles on the silver nanorod (AgNR) array PDMS substrate, to enhance the Raman signal of P. aeruginosa bacteria due to the formation of high density 'hot spots' among the AgNR arrays which provides better entrapment and increases the net effective contact area of bacteria with the metal surface. PMID- 26144848 TI - Ahead of print: Reducing time to publication for accepted manuscripts. PMID- 26144849 TI - Vitamin D and skin diseases: A review. PMID- 26144850 TI - A randomized controlled trial to compare cure and relapse rate of paucibacillary multidrug therapy with monthly rifampicin, ofloxacin, and minocycline among paucibacillary leprosy patients in Agra District, India. AB - OBJECTIVES: To study cure rate and relapse rate of standard World Health Organization paucibacillary multidrug therapy (PB-MDT) with monthly rifampicin, ofloxacin, and minocycline for six months (ROM-6) among paucibacillary leprosy patients. METHODS: A total of 268 patients, detected during active search in Agra district during 2001-2004, who had paucibacillary (PB) leprosy having 1-5 skin lesions and/or one nerve thickening/tenderness, were allocated, using random number tables, to two treatment groups; PB-MDT and ROM-6. On the first day of the month, dose of PB-MDT and of the ROM were given under supervision for 6 months. After completion of drug therapy, patients were followed every 6 months for first 5 years and later annually for next 3 years for monitoring disease status, cure rates, reactions and relapses. Cetai sigmathetaualpharhoepsilon test was used to compare relapse rates. RESULTS: The cure rate at 2 years was 99% in ROM-6 and 97.0% in PB-MDT group, of those who completed treatment and the difference was statistically not significant. At 5 years, only 88 patients in PB-MDT group and 90 patients in ROM-6 group could be followed; all were observed to be cured. However, during the period of 5-8 years, 3 of 67 patients in PB-MDT group and 1 of 73 in ROM-6 group were observed to have relapsed. In all, 10 relapses were noted (3 in ROM-6 and 7 in PB-MDT group) giving a relapse rate of 1.10/100 person years in PB-MDT and 0.435/100 person years in ROM groups (P = 0.053 ; statistically not significant). Of the 10 relapses, 5 occurred within 5 years (3 in PB-MDT group and 2 in ROM-6), 4 during 5-8 years (3 in PB-MDT and 1 in ROM-6), and 1 occurred in MDT group after 8 years. LIMITATION: A number of patients were lost to follow up after release from treatment and thus actual number of relapses in the study could not be assessed. Additionally, diagnosis was purely clinical and histology could not be done for reasons related to functional difficulties in the field. CONCLUSION: The study shows that PB-MDT and ROM-6 have almost similar acceptability, cure rate and relapse rate. PMID- 26144851 TI - The reservoir effect of topical steroids in vitiliginous skin: A cross-sectional study. AB - BACKGROUND: Prolonged and frequent use of topical steroids may lead to decrease in efficacy as well as many local adverse effects. Stratum corneum has a unique property of reservoir effect. AIMS: To study the reservoir effect of topical steroids in a steroid-responsive condition which may enable a decrease in the dosing frequency of topical steroids. METHODS: A cross-sectional study design was used. Patients with at least three vitiliginous patches of more than 2 cm 2 present over the trunk or limbs were included. Exclusion criteria were topical or systemic corticosteroid use within the previous 4 weeks, antihistamine use within the previous 7 days, history of any allergy in the past and immunosuppression. Clobetasol propionate cream was applied on the first vitiliginous area (site A) and fluticasone propionate ointment was applied on the second vitiliginous area (site B). The third vitiliginous area, site C (control site) was left without applying any medication. Histamine-induced wheal suppression test was performed on each site, at the same time of the day, on every consecutive day following steroid application, until the values obtained at sites A and B approached those obtained at site C. SPSS software for Windows, version 16.0 was used for statistical analysis. The mean and standard deviation of the various studied parameters were calculated for various treatment groups and compared using analysis of variance (ANOVA) test. RESULTS: Forty patients were included in the study. The average wheal volumes and average erythema sizes at sites A and B were significantly smaller than the corresponding values at site C for up to 5 days after applying medication (P < 0.001). LIMITATIONS: The presence of a cutaneous reservoir of topical steroid was confirmed based on its suppressive effect on the wheal and flare response to histamine. It is not certain that the concentration that suppresses histamine-induced wheal and flare is sufficient for therapeutic efficacy in vitiligo. CONCLUSION: The reservoir effect of topical clobetasol propionate and fluticasone propionate persisted for 5 days in vitiliginous skin. Hence, it may be possible to reduce the frequency of topical steroid application in vitiligo. PMID- 26144852 TI - Vascular patterns in cutaneous leishmaniasis: A videodermatoscopic study. PMID- 26144853 TI - Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome). PMID- 26144854 TI - The effects of normobaric oxygen therapy on patients with periorbital darkening: An open, uncontrolled trial. PMID- 26144855 TI - Dermatological adverse reactions to cancer chemotherapy. PMID- 26144858 TI - Observed and unobserved correlation between crash avoidance manoeuvers and crash severity. AB - Understanding drivers' responses to critical events, analyzing drivers' abilities to perform corrective manoeuvers, and investigating the correlation between these manoeuvers and crash severity provide the opportunity of increasing the knowledge about how to avoid crash occurrence or at least mitigate crash severity. We extend existing research on the determinants of engaging in crash avoidance manoeuvers by considering that observable and unobservable factors relate to both the selection of corrective manoeuvers and the severity outcome. Accordingly, we propose a joint multinomial-logit ordered-probit model of single-vehicle crashes extracted from the NASS GES database for the years 2005-2009. Results show (1) the existence of unobserved correlation between crash avoidance manoeuvers and crash severity, and (2) the link between drivers' attributes, risky driving behaviour, road characteristics, and environmental conditions, with the propensity to engage in crash avoidance manoeuvers and experience severe crash outcomes. PMID- 26144859 TI - Novel dietary lipid-based self-nanoemulsifying drug delivery systems of paclitaxel with p-gp inhibitor: implications on cytotoxicity and biopharmaceutical performance. AB - OBJECTIVES: This work describes the development and characterization of novel self-nanoemulsifying drug delivery systems (SNEDDS) employing polyunsaturated fatty acids for enhancing the oral bioavailability and anticancer activity of paclitaxel (PTX) by coadministration with curcumin (Cu). METHODS: Preformulation studies endorsed sesame oil, labrasol, and sodium deoxycholate as lipid surfactants and cosurfactants based on their solubility for the drugs and spontaneity of emulsification to produce nanoemulsions. Further, phase titration studies were performed to identify a suitable nanoemulsion region for preparing the SNEDDS formulation. RESULTS: The prepared formulations were characterized through in vitro, in situ, and in vivo studies to evaluate the biopharmaceutical performance. In vitro drug release studies showed 2.8- to 3.4-fold enhancement in the dissolution rate of both drugs from SNEDDS as compared with the pure drug suspension. Cell line studies revealed 1.5- to 2.7-fold reduction in the cytotoxicity on MCF-7 cells by plain PTX-SNEDDS and PTX-Cu-SNEDDS vis-a-vis the PTX-suspension. In situ intestinal perfusion studies revealed significant augmentation in permeability and absorption parameters of drug from PTX-Cu-SNEDDS over the plain PTX-SNEDDS and PTX-suspension (p < 0.001). In vivo pharmacokinetic studies also showed a remarkable improvement (i.e., 5.8- to 6.3-fold) in the oral bioavailability (Cmax and AUC) of the drug from PTX-SNEDDS and PTX-Cu-SNEDDS vis a-vis the PTX-suspension. CONCLUSIONS: Overall, the studies corroborated superior biopharmaceutical performance of PTX-Cu-SNEDDS. PMID- 26144860 TI - Pulmonary haemorrhage due to an aortopulmonary collateral artery after arterial switch. AB - A neonate with transposition of the great arteries and intact ventricular septum presented without pulmonary over-circulation, and subsequently developed pulmonary haemorrhage after corrective surgery. Postoperative CT revealed an aortopulmonary collateral artery arising from the descending aorta, and we performed successful embolisation on postoperative day 9. Aggressive imaging modalities such as angiography and/or CT imaging with contrast can detect unexpected extra-pulmonary blood supply and guide further management. PMID- 26144861 TI - Scopolamine attenuates auditory cortex response. AB - CONCLUSION: Scopolamine, a tropane alkaloid drug that mainly acts as an antagonist of muscarinic acetylcholine receptors, was found to reduce the local field potentials (LFP) of auditory cortex (AC) evoked by tone and gap-offsets whose effects may compensate the cortical hyperexcitability related to tinnitus. OBJECTIVE: To study the effects of scopolamine on the AC and the inferior colliculus (IC) of awake rats in order to understand scopolamine's effect on tinnitus and gap detection. METHOD: Silent gaps (duration varied from 2-100 ms) embedded in otherwise continuous noise were used to elicit AC and IC response. Gap evoked AC and IC field potentials were recorded from awake rats before and after treatment of scopolamine (3 mg/kg, i.m.). RESULTS: Acute injection of scopolamine (3 mg/kg, i.m.) induced a significant reduction of the AC response, but not the IC response, to the offset of the gaps embedded in white noise. The results suggest that scopolamine may reduce AC neural synchrony. PMID- 26144862 TI - Mechanism of Oxygen Activation in a Flavin-Dependent Monooxygenase: A Nearly Barrierless Formation of C4a-Hydroperoxyflavin via Proton-Coupled Electron Transfer. AB - Understanding how flavin-dependent enzymes activate oxygen for their oxidation and oxygenation reactions is one of the most challenging issues in flavoenzymology. Density functional calculations and transient kinetics were performed to investigate the mechanism of oxygen activation in the oxygenase component (C2) of p-hydroxyphenylacetate 3-hydroxylase (HPAH). We found that the protonation of dioxygen by His396 via a proton-coupled electron transfer mechanism is the key step in the formation of the triplet diradical complex of flavin semiquinone and (*)OOH. This complex undergoes intersystem crossing to form the open-shell singlet diradical complex before it forms the closed-shell singlet C4a-hydroperoxyflavin intermediate (C4aOOH). Notably, density functional calculations indicated that the formation of C4aOOH is nearly barrierless, possibly facilitated by the active site arrangement in which His396 positions the proximal oxygen of the (*)OOH in an optimum position to directly attack the C4a atom of the isoalloxazine ring. The nearly barrierless formation of C4aOOH agrees well with the experimental results; based on transient kinetics and Eyring plot analyses, the enthalpy of activation for the formation of C4aOOH is only 1.4 kcal/mol and the formation of C4aOOH by C2 is fast (~10(6) M(-1) s(-1) at 4 degrees C). The calculations identified Ser171 as the key residue that stabilizes C4aOOH by accepting a hydrogen bond from the H(N5) of the isoalloxazine ring. Both Ser171 and Trp112 facilitate H2O2 elimination by donating hydrogen bonds to the proximal oxygen of the OOH moiety during the proton transfer. According to our combined theoretical and experimental studies, the existence of a positively charged general acid at the position optimized for facilitating the proton coupled electron transfer has emerged as an important catalytic feature for the oxygen activation process in flavin-dependent enzymes. PMID- 26144863 TI - Accurate Diffusion Coefficients of Organosoluble Reference Dyes in Organic Media Measured by Dual-Focus Fluorescence Correlation Spectroscopy. AB - Dual-focus fluorescence correlation spectroscopy (2fFCS) is a versatile method to determine accurate diffusion coefficients of fluorescent species in an absolute, reference-free manner. Whereas (either classical or dual-focus) FCS has been employed primarily in the life sciences and thus in aqueous environments, it is increasingly being used in materials chemistry, as well. These measurements are often performed in nonaqueous media such as organic solvents. However, the diffusion coefficients of reference dyes in organic solvents are not readily available. For this reason we determined the translational diffusion coefficients of several commercially available organosoluble fluorescent dyes by means of 2fFCS. The selected dyes and organic solvents span the visible spectrum and a broad range of refractive indices, respectively. The diffusion coefficients can be used as absolute reference values for the calibration of experimental FCS setups, allowing quantitative measurements to be performed. We show that reliable information about the hydrodynamic dimensions of the fluorescent species (including noncommercial compounds) within organic media can be extracted from the 2fFCS data. PMID- 26144864 TI - Balancing the Expression and Production of a Heterodimeric Protein: Recombinant Agkisacutacin as a Novel Antithrombotic Drug Candidate. AB - Agkisacucetin extracted from the venom of Agkistrodon acutus has been demonstrated to be a promising antithrombotic drug candidate in clinical studies due to its function as a novel platelet membrane glycoprotein (GP) Ib inhibitor. Agkisacucetin is a heterodimeric protein composed of alpha- and beta-subunits with seven disulphide bonds. Both subunits form inactive homodimeric products, which cause difficulties for recombinant production. In this study, Agkisacucetin alpha- and beta-subunits were inserted sequentially into the chromosome of Pichia pastoris at the mutant histidinol dehydrogenase gene and ribosomal DNA repeat sites, respectively. By optimizing the gene copies and productivity of each subunit by drug screening, we successfully obtained a recombinant strain with balanced expression of the two subunits. Using this strain, a yield greater than 100 mg/L recombinant Agkisacucetin in fed-batch fermentation was reached. The recombinant Agkisacucetin possessed extremely similar binding affinity to recombinant GPIb and human platelets in in vitro assays, and its ristocetin induced platelet aggregation activity ex vivo was identical to that of the extracted native Agkisacucetin, demonstrating that the yeast-derived Agkisacucetin could be an effective alternative to native Agkisacucetin. Moreover, this study provides an effective strategy for balancing the expression and production of heterodimeric proteins in P. pastoris. PMID- 26144865 TI - Coral transplantation triggers shift in microbiome and promotion of coral disease associated potential pathogens. AB - By cultivating turf algae and aggressively defending their territories, territorial damselfishes in the genus Stegastes play a major role in shaping coral-algal dynamics on coral reefs. The epilithic algal matrix (EAM) inside Stegastes' territories is known to harbor high abundances of potential coral disease pathogens. To determine the impact of territorial grazers on coral microbial assemblages, we established a coral transplant inside and outside of Stegastes' territories. Over the course of one year, the percent mortality of transplanted corals was monitored and coral samples were collected for microbial analysis. As compared to outside damselfish territories, Stegastes were associated with a higher rate of mortality of transplanted corals. However, 16S rDNA sequencing revealed that territorial grazers do not differentially impact the microbial assemblage of corals exposed to the EAM. Regardless of Stegastes presence or absence, coral transplantation resulted in a shift in the coral associated microbial community and an increase in coral disease associated potential pathogens. Further, transplanted corals that suffer low to high mortality undergo a microbial transition from a microbiome similar to that of healthy corals to that resembling the EAM. These findings demonstrate that coral transplantation significantly impacts coral microbial communities, and transplantation may increase susceptibility to coral disease. PMID- 26144866 TI - Biotreatment of chlorpyrifos in a bench scale bioreactor using Psychrobacter alimentarius T14. AB - Bacteria tolerant to high pesticide concentration could be used for designing an efficient treatment technology. Bacterial strains T14 was isolated from pesticide contaminated soil in mineral salt medium (MSM) and identified as Psychrobacter alimentarius T14 using 16S rRNA gene sequence analysis. Bench scale bioreactor was evaluated for biotreatment of high Chlorpyrifos (CP) concentration using P. alimentarius T14. Effect of various parameters on bioreactor performance was examined and optimum removal was observed at optical density (OD600 nm): 0.8; pH: 7.2; CP concentration: 300 mg L(-1) and hydraulic retention time: 48 h. At optimum conditions, 70.3/79% of CP/chemical oxygen demand (COD) removal was achieved in batch bioreactors. In addition, P. alimentarius T14 achieved 95/91, 62.3/75, 69.8/64% CP/COD removal efficiency with addition of CS (co-substrates), CS1 (yeast extract + synthetic wastewater), CS2 (glucose + synthetic wastewater) and CS3 (yeast extract), respectively. Addition of CS1 to bioreactor could accelerate CP removal rate up to many cycles with considerable efficiency. However, accumulation of 3, 5, 6-trichloro-2-pyridinol affects reactor performance in cyclic mode. First-order rate constant k1 0.062 h(-1) and t1/2 11.1 h demonstrates fast degradation. Change in concentration of total chlorine and nitrogen could be the result of complete mineralization. Photodegradation of CP in commercial product was more than its pure form. Commercial formulation accelerated photodegradation process; however no effect on biodegradation process was observed. After bio-photodegradation, negligible toxicity for seeds of Triticum aestivum was observed. Study suggests an efficient treatment of wastewater containing CP and its metabolites in batch bioreactors could be achieved using P. alimentarius. PMID- 26144868 TI - Electronic polymers and soft-matter-like broken symmetries in underdoped cuprates. AB - Empirical evidence in heavy fermion, pnictide and other systems suggests that unconventional superconductivity appears associated to some form of real-space electronic order. For the cuprates, despite several proposals, the emergence of order in the phase diagram between the commensurate antiferromagnetic state and the superconducting state is not well understood. Here we show that in this regime doped holes assemble in 'electronic polymers'. Within a Monte Carlo study, we find that in clean systems by lowering the temperature the polymer melt condenses first in a smectic state and then in a Wigner crystal both with the addition of inversion symmetry breaking. Disorder blurs the positional order leaving a robust inversion symmetry breaking and a nematic order, accompanied by vector chiral spin order and with the persistence of a thermodynamic transition. Such electronic phases, whose properties are reminiscent of soft-matter physics, produce charge and spin responses in good accord with experiments. PMID- 26144867 TI - A post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status. AB - Nervous system (NS) development relies on coherent upregulation of extensive sets of genes in a precise spatiotemporal manner. How such transcriptome-wide effects are orchestrated at the molecular level remains an open question. Here we show that 3'-untranslated regions (3' UTRs) of multiple neural transcripts contain AU rich cis-elements (AREs) recognized by tristetraprolin (TTP/Zfp36), an RNA binding protein previously implicated in regulation of mRNA stability. We further demonstrate that the efficiency of ARE-dependent mRNA degradation declines in the neural lineage because of a decrease in the TTP protein expression mediated by the NS-enriched microRNA miR-9. Importantly, TTP downregulation in this context is essential for proper neuronal differentiation. On the other hand, inactivation of TTP in non-neuronal cells leads to dramatic upregulation of multiple NS specific genes. We conclude that the newly identified miR-9/TTP circuitry limits unscheduled accumulation of neuronal mRNAs in non-neuronal cells and ensures coordinated upregulation of these transcripts in neurons. PMID- 26144869 TI - Effects of sex and dietary lysine on performances and serum and meat traits in finisher pigs. AB - A total of 160 Duroc*(Landrace*Large White) pigs, 50% barrows and 50% gilts, of 28.3 +/- 4.52 kg of BW were used to study the effect of lysine (Lys) restriction in the finisher period, on growth performances and serum and carcass and meat quality traits. The grower diet (from 30 to 90 kg BW) was slightly Lys-restricted (7.8 g standardised ileal digestible (SID) Lys/kg) in accordance with results from a previous trial. During the finisher period (90 to 130 kg BW), four experimental diets with decreasing SID Lys contents (6.3, 5.6, 4.2 and 3.2 g/kg) were tested. Each of the eight treatments (two sexes*four levels of Lys) was replicated five times. Each replicate was a pen with four pigs allocated together. When animals achieved 129 +/- 2.59 kg were slaughtered and carcass and meat characteristics were evaluated. No significant interaction sex*diet was found. During the finisher period, barrows grew faster (P<0.001) and ate more feed (P<0.001) but tended to be less efficient (P=0.055) than gilts. The Lys restriction affected linearly (P<0.001) all productive performance traits; daily BW gain and feed intake decreased and feed conversion ratio increased. Also, the concentration of serum urea at slaughter tended to be higher in barrows than in gilts (P=0.065) and was reduced quadratically by the restriction of Lys in feed (P<0.001). Carcasses from barrows had higher backfat thickness (P<0.01) and lower weight of main trimmed lean cuts (ham+shoulder+loin; P<0.05) than those from gilts. The Lys restriction during the finisher period decreased carcass yield (quadratic; P<0.001) and the weight of major cuts (linear; P<0.001). Sex and diet had limited effect on meat characteristics; the Lys restriction decreased quadratically the proportion of protein (P<0.01) and increased linearly the intramuscular fat (IMF) content (P<0.001). We can conclude that dietary Lys restriction during finisher period in pigs impaired growth performances and was not successful to increase the carcass fat deposition, although it could have positive effects on IMF proportion of pork. PMID- 26144870 TI - Low-gradient Severe Aortic Stenosis With Preserved Ejection Fraction. A Pathophysiologic Entity or a Methodologic Disparity? PMID- 26144871 TI - Work, Aging, and Risks to Family Life: The Case of Australia. AB - The relationship between work and family is considered with an emphasis on policy solutions. Australian policy is a case example in the context of international trends. A mismatch between policy initiatives and familial and personal priorities constitutes a new social risk associated with demographic and sociocultural development. Contemporary trends, both nationally and internationally, evidence solutions to the "problem of demographic aging" by adopting a form of economic instrumentalism. This restricts legitimate age identities to those associated with work and work-related activity. When applied to family life, such a focus runs the risk of reducing policy interest in intergenerational engagement to unpaid care roles, while personal development and age-related life priorities are ignored. The need for cultural adaptation to population aging is becoming accepted in policy debate and is considered here as an effective response to the personal, social, and economic risks of population aging and associated impacts on family life. PMID- 26144872 TI - Expression of immunohistochemical markers according to histological type in patients with early gastric cancer. AB - OBJECTIVE: We compared the biological characteristics of early gastric cancer (EGC) using immunohistochemical (IHC) staining among histological types. MATERIALS AND METHODS: IHC staining results were analyzed in 86 EGCs resected with endoscopic submucosal dissection to identify mucin phenotype and biological characteristics. RESULTS: The histological type was classified as tubular adenocarcinoma (TAC), mixed adenocarcinoma (MAC), or poorly cohesive carcinoma (PCC). Significant differences in MUC-2 (34.4% vs. 10.7%, p < 0.05) and MUC-5AC (59.4% vs. 85.7%, p < 0.05) expression were observed between TAC and PCC. The poorly cohesive component of MAC showed stronger immunoreactivity to CD10 (46.2% vs. 14.3%, p < 0.05) but weaker reactivity to MUC-5AC (57.7% vs. 85.7%, p < 0.05), compared to that of PCC. E-cadherin and beta-catenin expression levels significantly decreased in the poorly cohesive component of MAC (15.4% vs. 90.6%, p < 0.05; 7.7% vs. 90.6%, p < 0.05, respectively) and PCC (10.7% vs. 90.6%, p < 0.05; 14.3% vs. 90.6%, p < 0.05, respectively), compared to TAC. However, vascular endothelial growth factor expression significantly increased in the poorly cohesive component of MAC (42.3% vs. 9.4%, p < 0.05) and PCC (39.3% vs. 9.4%, p < 0.05), compared to TAC. CONCLUSION: IHC analysis showed that EGC histological types differ in terms of mucin phenotype and biological characteristics. The poorly cohesive components showed decreased E-cadherin and beta-catenin expression levels and increased vascular endothelial growth factor expression. These characteristics may contribute to the poor prognosis of patients with MAC and PCC. PMID- 26144873 TI - The STAT3 Inhibitor Galiellalactone Effectively Reduces Tumor Growth and Metastatic Spread in an Orthotopic Xenograft Mouse Model of Prostate Cancer. AB - Signal transducer and activator of transcription 3 (STAT3) is known to be involved in the progression of prostate cancer (PCa) and is a key factor in drug resistance and tumor immunoescape. As a result, it represents a promising target for PCa therapy. We studied the effects of the STAT3 inhibitor galiellalactone (GL) on tumor growth and metastatic spread in vitro and in vivo. The effect of GL on cell viability, apoptosis, and invasion was studied in vitro using androgen independent DU145 and DU145-Luc cell lines. For in vivo studies, mice were injected orthotopically with DU145-Luc cells and treated with daily intraperitoneal injections of GL for 6 wk. GL significantly reduced the growth of the primary tumor and the metastatic spread of PCa cells to regional and distal lymph nodes in vivo. Treatment with GL also resulted in decreased cell proliferation and increased apoptosis compared with controls. In vitro, GL reduces the viability and invasive abilities of DU145-Luc cells and induces apoptosis. Our results showed that tumor growth and early metastatic dissemination of PCa can be significantly reduced by GL, indicating its potential use as a therapeutic compound in advanced metastatic PCa. PATIENT SUMMARY: In this study, we tested the STAT3 inhibitor galiellalactone (GL) in an animal model of PCa. We found that mice treated with GL had smaller primary tumors and decreased lymph node metastases compared with mice treated with vehicle. GL has potential for treating advanced metastatic PCa. PMID- 26144874 TI - Re: Syed Johar Raza, Timothy Wilson, James O. Peabody, et al. Long-term Oncologic Outcomes Following Robot-assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium. Eur Urol 2015;68:721-8. PMID- 26144875 TI - Transition to Adulthood for Young People with Medical Complexity: An Integrative Literature Review. AB - This article explores how the empirical literature on the transition to adulthood for young people with medical complexity can inform nursing and advanced practice nursing. An integrative literature review informed by Meleis' Transition Theory and Bronfenbrenner's Bioecological Theory of Human Development was conducted including 11 studies and yielded three themes: it's like falling off a cliff, the paradox of independence, and it takes a village. The findings demonstrated a need for an increased focus on the process of transition and transfer for this complex population. Recommendations for pediatric nurses and advanced practice nurses based on these findings focus on advocacy, capacity-building, education, and program development and evaluation. Recommendations for future research are offered with a focus on determinants of health, psychosocial concerns, and program development and evaluation. PMID- 26144876 TI - Type 1 Diabetes Among East African Immigrant and Nonimmigrant Black Youth in the U.S. AB - Type 1 diabetes has not previously been described in East African immigrant youth in the United States. The purpose of this study was to compare East African immigrant and nonimmigrant Black youth with type 1 diabetes. Among other clinical and demographic differences, estimated prevalence of type 1 diabetes was nearly four times higher among East African youth in King County, Washington (6.20/1000, 95% confidence interval (CI) [4.49, 7.91] vs. 1.56/1000, 95% CI [1.03, 2.09]) compared to nonimmigrant Black youth. These observations are lost within the Black/African American race classification and additional work is needed to confirm and further explore these findings. PMID- 26144877 TI - Vaccines for women for preventing neonatal tetanus. AB - BACKGROUND: Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin that stimulates the production of antitoxin. OBJECTIVES: To assess the effectiveness of tetanus toxoid, administered to women of reproductive age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), CENTRAL (The Cochrane Library 2015, Issue 1), PubMed (1966 to 28 January 2015), EMBASE (1974 to 28 January 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of reproductive age on numbers of neonatal tetanus cases and deaths. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Two effectiveness trials (9823 infants) and one safety trial (48 mothers) were included. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. For our primary outcomes, there was no high-quality evidence according to GRADE assessments.One study (1182 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. A single dose did not provide significant protection against neonatal tetanus deaths, (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.26 to 1.24; 494 infants; GRADE: low-quality evidence). However, a two- or three-dose course did provide protection against neonatal deaths, (RR 0.02, 95% CI 0.00 to 0.30; 688 infants; GRADE: moderate-quality evidence). Administration of a two- or three dose course resulted in significant protection when all causes of death are considered as an outcome (RR 0.31, 95% CI 0.17 to 0.55; 688 infants; GRADE: moderate-quality evidence). No effect was detected on causes of death other than tetanus. Cases of neonatal tetanus after at least one dose of tetanus toxoid were reduced in the tetanus toxoid group, (RR 0.20, 95% CI 0.10 to 0.40; 1182 infants; GRADE: moderate-quality evidence).Another study, involving 8641 children, assessed the effectiveness of tetanus-diphtheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. Neonatal mortality was reduced in the tetanus-diphtheria toxoid group (RR 0.68, 95% CI 0.56 to 0.82). In preventing deaths at four to 14 days, neonatal mortality was reduced again in the tetanus-diphtheria toxoid group (RR 0.38, 95% CI 0.27 to 0.55). The quality of evidence as assessed using GRADE was found to be low.The third small trial assessed that pain at injection site was reported more frequently among pregnant women who received tetanus diphtheria acellular pertussis than placebo (RR 5.68, 95% CI 1.54 to 20.94; GRADE: moderate-quality evidence). AUTHORS' CONCLUSIONS: Available evidence supports the implementation of immunisation practices on women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. PMID- 26144878 TI - Operative management of portal annular pancreas during pancreaticoduodenectomy. PMID- 26144879 TI - Transient and permanent hypocalcemia after total thyroidectomy: Early predictive factors and long-term follow-up results. AB - BACKGROUND: Post-thyroidectomy hypocalcemia is among the most common complications of total thyroidectomy. The purpose of this study was to evaluate early predictive factors and long-term changes in intact parathyroid hormone (iPTH) levels in patients with transient and permanent hypocalcemia after total thyroidectomy. PATIENTS AND METHODS: A total of 349 consecutive patients who underwent total thyroidectomy with or without neck dissection between 2009 and 2011 were reviewed. PTH, total calcium (Ca), and ionized Ca (iCa) levels were evaluated at 1 hour, and 1, 3, 5, and 7 days, and 1, 3, 6, and 12 months postoperatively. Biochemical profiles at 1 hour after total thyroidectomy in patients with transient and permanent hypocalcemia were compared. Patients with postoperative hypocalcemia were followed for 12 months. RESULTS: Lesser preoperative serum levels of Ca and more extensive surgery were significantly associated with postoperative hypocalcemia (P < .05). The absolute level and relative decline (%) in iPTH at 1 hour were the most reliable predictors of postoperative hypocalcemia according to the receiver operating characteristics curve, with a threshold of 10.42 pg/mL and 70%. Sensitivity and specificity of the predictors were 83.4% (95% CI, 76.4-89.1), 100% (95% CI, 84.6-100.0), 84.1 (95% CI, 77.2-89.7), and 95.5% (95% CI, 77.2-99.9), respectively. Parathyroid function recovered in the first month after total thyroidectomy in 78 of 99 patients (79%) with transient hypocalcemia. However, 46 of 61 patients (74%) with a subnormal iPTH level at 3 months after surgery had permanent hypocalcemia. CONCLUSION: Mean postoperative PTH level and the mean relative decline in PTH measured 1 hour postoperatively were the most reliable predictors of postoperative or permanent hypocalcemia. PMID- 26144880 TI - Social media is a necessary component of surgery practice. AB - Social media is a necessary component of the practice of surgery. Each surgeon must embrace the power and potential of social media and serve as a guide or content expert for patients and other health care providers to facilitate and share responsible use of the various media available. Social media facilitates rapid communication of information not only across providers but also between patients and providers. The power of social media has the potential to improve consultation and collaboration, facilitate patient education, and expand research efforts; moreover, by harnessing its potential, the appropriate use of many of the avenues of social media also can be used to disseminate campaigns to increase disease awareness and communicate new research findings and best-practice guidelines. Because its reach is so broad within as well as outside the censorship of medical experts, professional oversight and engagement is required to maximize responsible use. Staying consistent with our history of surgery, rich in innovation and technologic advancement, surgeons must get to the front of this evolving field and direct the path of social media as it applies to the practice of surgery rather than take a passive role. PMID- 26144881 TI - Mutism in non-catatonic schizophrenia: Psychotic symptom and adaptive behavioral strategy. PMID- 26144882 TI - Severity and persistence versus type of childhood adversity in non-affective first-episode psychosis. PMID- 26144883 TI - Internal Ribosome Entry Site-Based Bicistronic In Situ Reporter Assays for Discovery of Transcription-Targeted Lead Compounds. AB - Although transgene-based reporter gene assays have been used to discover small molecules targeting expression of cancer-driving genes, the success is limited due to the fact that reporter gene expression regulated by incomplete cis-acting elements and foreign epigenetic environments does not faithfully reproduce chemical responses of endogenous genes. Here, we present an internal ribosome entry site-based strategy for bicistronically co-expressing reporter genes with an endogenous gene in the native gene locus, yielding an in situ reporter assay closely mimicking endogenous gene expression without disintegrating its function. This strategy combines the CRISPR-Cas9-mediated genome-editing tool with the recombinase-mediated cassette-exchange technology, and allows for rapid development of orthogonal assays for excluding false hits generated from primary screens. We validated this strategy by developing a screening platform for identifying compounds targeting oncogenic eIF4E, and demonstrated that the novel reporter assays are powerful in searching for transcription-targeted lead compounds with high confidence. PMID- 26144885 TI - AMPK Activation via Modulation of De Novo Purine Biosynthesis with an Inhibitor of ATIC Homodimerization. AB - 5-Aminoimidazole-4-carboxamide ribonucleotide (known as ZMP) is a metabolite produced in de novo purine biosynthesis and histidine biosynthesis, but only utilized in the cell by a homodimeric bifunctional enzyme (called ATIC) that catalyzes the last two steps of de novo purine biosynthesis. ZMP is known to act as an allosteric activator of the cellular energy sensor adenosine monophosphate activated protein kinase (AMPK), when exogenously administered as the corresponding cell-permeable ribonucleoside. Here, we demonstrate that endogenous ZMP, produced by the aforementioned metabolic pathways, is also capable of activating AMPK. Using an inhibitor of ATIC homodimerization to block the ninth step of de novo purine biosynthesis, we demonstrate that the subsequent increase in endogenous ZMP activates AMPK and its downstream signaling pathways. We go on to illustrate the viability of using this approach to AMPK activation as a therapeutic strategy with an in vivo mouse model for metabolic disorders. PMID- 26144884 TI - Metal Ion-Mediated Nucleobase Recognition by the ZTP Riboswitch. AB - The ZTP riboswitch is a widespread family of regulatory RNAs that upregulate de novo purine synthesis in response to increased intracellular levels of ZTP or ZMP. As an important intermediate in purine biosynthesis, ZMP also serves as a proxy for the concentration of N10-formyl-tetrahydrofolate, a key component of one-carbon metabolism. Here, we report the structure of the ZTP riboswitch bound to ZMP at a resolution of 1.80 A. The RNA contains two subdomains brought together through a long-range pseudoknot further stabilized through helix-helix packing. ZMP is bound at the subdomain interface of the RNA through a set of interactions with the base, ribose sugar, and phosphate moieties of the ligand. Unique to nucleobase recognition by RNAs, the Z base is inner-sphere coordinated to a magnesium cation bound by two backbone phosphates. This interaction, along with steric hindrance by the backbone, imparts specificity over chemically similar compounds such as ATP/AMP. PMID- 26144886 TI - Molecular cloning and characterization of brain and ovarian cytochrome P450 aromatase genes in the catfish Heteropneustes fossilis: Sex, tissue and seasonal variation in, and effects of gonadotropin on gene expression. AB - Cytochrome P450 aromatase (Cyp19arom) is the rate-limiting enzyme controlling estrogen biosynthesis, coded by Cyp19a1 in most gnathostomes. Most teleosts have two forms expressed differentially in ovary (cyp19a1a) and neural tissue (cyp19a1b). In this study, full length cDNAs of 2006 bp and 1913 bp with ORFs of 1575 bp and 1488 bp were isolated from the brain and ovary, respectively, of the catfish Heteropneustes fossilis, an air-breathing species with high aquaculture potential. The ORFs encode predicted proteins of 495 and 524 amino acid residues, respectively. The proteins show 62% identity with each other and cluster in two distinct clades (the brain type and ovary type) in the teleost taxon, separated from the tetrapod type. In the in situ localization study, both cyp19a1a and cyp19a1b transcripts were localized in the brain but the signal intensity was higher for the brain type paralog. The transcript signals were observed in the radial glial cells and in neuronal populations of the dorso-lateral region of the telencephalon, pre-tectum, hypothalamus and medulla oblongata. In the ovary, both paralogs were expressed in the follicular layer with a high signal intensity of the ovarian type (cyp19a1a). The differential expression of the gene paralogs was evident from qPCR analysis. Cyp19a1b has relatively a high abundance in the female brain, followed by other peripheral tissues (gonads, liver, gill, kidney and muscle). On the other hand, cyp19a1a has relatively a high transcript abundance in the ovary and female brain, followed by the testis and male brain, and female liver and muscle. The expression was low in male liver and muscle, and the lowest in the gill and kidney. The expression of the two paralogs exhibit brain regional differences; both types have relatively a high transcript abundance in telencephalon-preoptic area with the cyp19a1b expression higher in females than males. In hypothalamus, the expression of both types is higher in males than females. In medulla, the expression of the cyp19a1b is higher than cyp19a1a, and the transcript abundance of the ovarian type is higher in females than males. The expression of the gene paralogs elicits significant seasonal variations in the ovary and brain. In both tissues, the expression increases from the resting to preparatory phases, and decreases through the prespawning phase to low levels in spawning phase. In vivo and/or in vitro treatments with human chorionic gonadotropin (hCG) stimulated the expression of the gene paralogs in the brain and ovary, time-dependently. In conclusion, both paralogs have an overlapping distribution at different levels of the brain-pituitary-gonad axis and may function as a single functional unit as far as the estrogen synthesis is concerned. PMID- 26144887 TI - Reduced facial emotion recognition in overweight and obese children. AB - OBJECTIVE: Emotional problems often co-occur in overweight or obese children. However, questions of whether emotion recognition deficits are present and how they are reflected have only been sparsely investigated to date. METHODS: Therefore, the present study included 33 overweight and obese as well as 33 normal weight elementary school children between six and ten years that were matched for sex, age and socioeconomic status. Participants were shown different emotional faces of a well-validated set of stimuli on a computer screen, which they categorized and then rated on an emotional intensity level. Key measures were categorization performance along with reaction times and emotional intelligence as well as emotional eating questionnaire ratings. RESULTS: Overweight children exhibited lower categorization accuracy as well as longer reaction times as compared to normal weight children, while no differences in intensity ratings occurred. Reaction time to neutral facial expressions was negatively related to intrapersonal and interpersonal emotional intelligence and emotional eating correlated negatively with accuracy for recognizing sad expressions. CONCLUSION: Facial emotion decoding difficulties seem to be of importance in overweight and obese children and deserve further consideration in terms of their exact impact on social functioning as well as on the maintenance of elevated body weight during child development. PMID- 26144889 TI - Peripheral and central blockade of interleukin-6 trans-signaling differentially affects sleep architecture. AB - The immune system is known to essentially contribute to the regulation of sleep. Whereas research in this regard focused on the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor, the role of interleukin-6 (IL-6) in sleep regulation has been less intensely studied, probably due to the so far seemingly ambiguous results. Yet, this picture might simply reflect that the effects of IL-6 are conveyed via two different pathways (with possibly different actions), i.e., in addition to the 'classical' signaling pathway via the membrane bound IL-6 receptor (IL-6R), IL-6 stimulates cells through the alternative 'trans signaling' pathway via the soluble IL-6R. Here, we concentrated on the contributions of the trans-signaling pathway to sleep regulation. To characterize this contribution, we compared the effect of blocking IL-6 trans-signaling (by the soluble gp130Fc fusion protein) in the brain versus body periphery. Thus, we compared sleep in transgenic mice expressing the soluble gp130Fc protein only in the brain (GFAP mice) or in the body periphery (PEPCK mice), and in wild type mice (WT) during a 24-h period of undisturbed conditions and during 18 h following a 6-h period of sleep deprivation. Compared with WT mice, PEPCK mice displayed less sleep, particularly during the late light phase, and this was accompanied by decreases in slow wave sleep (SWS) and rapid eye movement (REM) sleep. Following sleep deprivation PEPCK mice primarily recovered REM sleep rather than SWS. GFAP mice showed a slight decrease in REM sleep in combination with a profound and persistent increase in EEG theta activity. In conclusion, peripheral and central nervous IL-6 trans-signaling differentially influences brain activity. Peripheral IL-6 trans-signaling appears to more profoundly contribute to sleep regulation, mainly by supporting SWS. PMID- 26144888 TI - The prebiotics 3'Sialyllactose and 6'Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis. AB - There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stressor exposure significantly alters gut microbiota community structure. We tested whether oligosaccharides naturally found in high levels in human milk, which have been reported to impact brain development and enhance the growth of beneficial commensal microbes, would prevent stressor-induced alterations in gut microbial community composition and attenuate stressor-induced anxiety-like behavior. Mice were fed standard laboratory diet, or laboratory diet containing the human milk oligosaccharides 3'Sialyllactose (3'SL) or 6'Sialyllactose (6'SL) for 2 weeks prior to being exposed to either a social disruption stressor or a non-stressed control condition. Stressor exposure significantly changed the structure of the colonic mucosa-associated microbiota in control mice, as indicated by changes in beta diversity. The stressor resulted in anxiety-like behavior in both the light/dark preference and open field tests in control mice. This effect was associated with a reduction in immature neurons in the dentate gyrus as indicated by doublecortin (DCX) immunostaining. These effects were not evident in mice fed milk oligosaccharides; stressor exposure did not significantly change microbial community structure in mice fed 3'SL or 6'SL. In addition, 3'SL and 6'SL helped maintain normal behavior on tests of anxiety-like behavior and normal numbers of DCX+ immature neurons. These studies indicate that milk oligosaccharides support normal microbial communities and behavioral responses during stressor exposure, potentially through effects on the gut microbiota-brain axis. PMID- 26144890 TI - Sexually dimorphic innate immunological responses of pre-pubertal Brahman cattle following an intravenous lipopolysaccharide challenge. AB - This study was designed to characterize potential sexually dimorphic immunological responses following a lipopolysaccharide (LPS) challenge in beef cattle. Six female (heifers) and five male (bulls) Brahman calves (average age=253 +/- 19.9 and 288 +/- 47.9 days; average body weight=194 +/- 11 kg and 247 +/- 19 kg for heifers and bulls, respectively) were challenged with LPS (0.25 MUg LPS/kg body weight). Following administration of LPS, all cattle displayed increased sickness behavior beginning at 0.5h, with heifers on average displaying less sickness behavior than bulls. A febrile response was observed in all animals following LPS administration, with a maximum response observed from 4 to 5.5h. The average rectal temperature response was greater in heifers than bulls. In all cattle there were elevated serum concentrations of cortisol from 0.5 to 8h, TNF alpha from 1 to 2.5h, IL-6 from 2 to 8h, and IFN-gamma from 2.5 to 7h after LPS challenge. Additionally, serum concentrations of TNF-alpha were greater in heifers than bulls from 1.5 to 2h after the LPS challenge. Concentrations of IFN gamma were also greater on average in bulls than heifers. Leukopenia occurred from 1 to 8h, with a decreased neutrophil to lymphocyte ratio for the first 5h among all calves. These data demonstrate the existence of a sexually dimorphic acute-phase response in pre-pubertal Brahman calves. Specifically, heifers may have a more robust acute response to LPS challenge, even though bulls display more signs of sickness. PMID- 26144891 TI - Specific faecal antibody responses in sheep infected with Mycobacterium avium subspecies paratuberculosis. AB - Many studies have examined the serum antibody response to Mycobacterium avium subspecies paratuberculosis (MAP) infection in cases of Johne's disease (JD), but there are no reports on the mucosal antibody response. Faecal immunoglobulin (Ig) G and IgA ELISA responses were examined from sheep experimentally inoculated with MAP for up to 23 months post inoculation (PI). Corresponding serum IgG responses and the presence of viable MAP shed in faeces were also examined. The sheep were divided into three groups: (i) "un-inoculated controls" (n=10), (ii) "clinical cases" (n=8) which were inoculated animals that developed clinical disease and had moderate to high levels of MAP shedding and (iii) "survivors" (n=11) which were inoculated animals from which MAP could not be cultured from tissues at the conclusion of the trial. Serum IgG responses gradually increased in all inoculated animals, peaking at 12-16 months PI. A significant increase in the levels of MAP-specific faecal IgG and IgA was measured in the survivors at 16 and 17 months PI, while levels in the un-inoculated controls and clinical cases remained at baseline levels. The detection of faecal Ig in the survivors coincided with the removal of sheep that developed clinical disease. The data suggest that some sheep produced MAP-specific IgG and IgA in the intestinal mucosa, which was released into their faeces. We hypothesise that the survivors produced faecal Ig as a direct response to ingestion of MAP associated with environmental contamination from clinical cases. Thus MAP specific mucosal antibodies may play a previously unreported role as part of a protective response triggered by environmental exposure. PMID- 26144892 TI - Detection of Helicobacter pylori CagA EPIYA in gastric biopsy specimens and its relation to gastric diseases. AB - CagA of Helicobacter pylori undergoes tyrosine phosphorylation in a region containing differing numbers of repeat sequences (EPIYAs), which can result in a modulation of the inflammatory response. This study investigated whether the presence of CagA EPIYA variations in strains of H. pylori that are positive for this region contributes to differing degrees of disease severity in the gastric mucosa. In this study, 157 H. pylori-positive patients were included, and of those, 40.8% (64/157) were infected with cagA-positive strains, which were assayed for the presence of CagA EPIYA-ABC, EPIYA-ABCC, and EPIYA-ABCCC. Peptic ulcers were significantly more prevalent in patients infected with strains containing CagA EPIYA-ABCC/ABCCC than in those with CagA EPIYA ABC strains (P=0.044). This suggests that the number of repetitions of EPIYA-C influences the development of gastroduodenal lesions, highlighting the importance and usefulness of evaluating the cagA gene sequence when making therapeutic intervention decisions in patients infected with H. pylori. PMID- 26144893 TI - Is Shock Index a Valid Predictor of Mortality in Emergency Department Patients With Hypertension, Diabetes, High Age, or Receipt of beta- or Calcium Channel Blockers? AB - STUDY OBJECTIVE: Shock index is a widely reported tool to identify patients at risk for circulatory collapse. We hypothesize that old age, diabetes, hypertension, and beta- or calcium channel blockers weaken the association between shock index and mortality. METHODS: This was a cohort study of all first time emergency department (ED) visits between 1995 and 2011 (n=111,019). We examined whether age 65 years or older, diabetes, hypertension, and use of beta- or calcium channel blockers modified the association between shock index and 30 day mortality. RESULTS: The 30-day mortality was 3.0%. For all patients, with shock index less than 0.7 as reference, a shock index of 0.7 to 1 had an adjusted odds ratio (OR) of 2.9 (95% confidence interval [CI] 2.7 to 3.2) for 30-day mortality, whereas shock index greater than or equal to 1 had an OR of 10.5 (95% CI 9.3 to 11.7). The crude OR for shock index greater than or equal to 1 in patients aged 65 years or older was 8.2 (95% CI 7.2 to 9.4) compared with 18.9 (95% CI 15.6 to 23.0) in younger patients. beta- Or calcium channel-blocked patients had an OR of 6.4 (95% CI 4.9 to 8.3) versus 12.3 (95% CI 11.0 to 13.8) in nonusers and hypertensive patients had an OR of 8.0 (95% CI 6.6 to 9.4) versus 12.9 (95% CI 11.1 to 14.9) in normotensive patients. Diabetic patients had an OR of 9.3 (95% CI 6.7 to 12.9) versus 10.8 (95% CI 9.6 to 12.0) in nondiabetic patients. A shock index of 0.7 to 1 was associated with ORs greater than 1 (range 2.2 to 3.1), with no evident differences within subgroups. The adjusted analyses showed similar ORs. CONCLUSION: Shock index is independently associated with 30 day mortality in a broad population of ED patients. Old age, hypertension, and beta- or calcium channel blockers weaken this association. However, a shock index greater than or equal to 1 suggests substantial 30-day mortality risk in all ED patients. PMID- 26144894 TI - Long-term safety and efficacy of varicella vaccination in children with juvenile idiopathic arthritis treated with biologic therapy. AB - OBJECTIVE: To evaluate the long-term safety and efficacy of varicella vaccination in children with juvenile idiopathic arthritis (JIA) treated with biologics. METHODS: We performed a prospective study with long term follow up. Six patients with JIA treated with biologics, received 2 doses of varicella vaccine. Before vaccination, JIA was stable on therapy and peripheral blood lymphocyte populations were within normal limits. After vaccination, children were followed for disease activity, infections and production of protective antibodies. RESULTS: There were no serious side effects after vaccination and no varicella infection. Disease activity remained stable. Five patients (83%) produced protective antibodies against varicella virus 6 weeks after the second vaccination. One patient with low level of protective antibodies got mild varicella infection 4 months after the second vaccination. CONCLUSION: Varicella vaccination appears to be safe in our group of six JIA patients treated with biologics. Vaccination does not always protect against varicella infection. PMID- 26144895 TI - Efficacy of antigen dosage on the hepatitis B vaccine response in infants born to hepatitis B-uninfected and hepatitis B-infected mothers. AB - OBJECTIVE: To compare the safety and immunogenicity of two dosages of recombinant hepatitis B (HB) vaccine administered to infants born to HB-uninfected and HB infected mothers. METHODS: A phase III, controlled, single-blinded clinical trial was conducted with 506 healthy newborns. The newborns were assigned to three groups based on maternal levels of HB surface antigen (HBsAg) and HB e antigen (HBeAg): Group A, HBsAg negative; Group B, HBsAg positive and HBeAg negative; and Group C, HBsAg positive and HBeAg positive. Three doses of 10 or 5 MUg recombinant HB vaccine were randomly administered by 1:1 within 24 h after birth, at 1 month and at 6 months. Safety data and pre- and postvaccination blood samples were collected. RESULTS: A total of 326, 93, and 87 subjects were included in Groups A, B, and C, respectively. Both dosages of HB vaccine were well tolerated by all subjects. The most common injection-site adverse reactions (ARs) and systemic ARs were pain and fever. After 1 month of the third dose, the Group A infants who received the 10 MUg HB vaccine achieved a higher geometric mean concentration (GMC) of HB surface antibody (anti-HBs) than those who received the 5 MUg dosage. Maternal anti-HBs serostatus did not influence HB vaccine immunogenicity at either dosage. In contrast, there was no significant difference in the anti-HBs seroconversion rate, GMCs, or estimated vaccine efficacy (EVE) against perinatal transmission between Groups B and C, regardless of dosage. However, the seroconversion rate and EVE of the 5 MUg HB vaccine was lower in Group C than in Group B. CONCLUSIONS: Both dosages of the HB vaccine were well tolerated and elicited a good immune response in infants of Group A, regardless of the maternal anti-HBs serostatus. EVE did not significantly differ between Groups B and C. Clinicaltrials.gov identifier: NCT02152709. PMID- 26144897 TI - Discounting in the evaluation of the cost-effectiveness of a vaccination programme: A critical review. AB - Discounting future costs and health benefits usually has a large effect on results of cost-effectiveness evaluations of vaccination because of delays between the initial expenditure in the programme and the health benefits from averting disease. Most guidelines currently recommend discounting both costs and health effects at a positive, constant, common rate back to a common point in time. A review of 84 published economic evaluations of vaccines found that most of them apply these recommendations. However, both technical and normative arguments have been presented for discounting health at a different rate to consumption (differential discounting), discounting at a rate that changes over time (non-constant discounting), discounting intra-generational and inter generational effects at a different rate (two-stage discounting), and discounting the health gains from an intervention to a different discount year from the time of intervention (delayed discounting). These considerations are particularly acute for vaccines, because their effects can occur in a different generation from the one paying for them, and because the time of vaccination, of infection aversion, and of disease aversion usually differ. Using differential, two-stage or delayed discounting in model-based cost-effectiveness evaluations of vaccination raises technical challenges, but mechanisms have been proposed to overcome them. PMID- 26144896 TI - Reasons for low influenza vaccination coverage among adults in Puerto Rico, influenza season 2013-2014. AB - BACKGROUND: Influenza vaccination is recommended annually for all persons 6 months and older. Reports of increased influenza-related morbidity and mortality during the 2013-2014 influenza season raised concerns about low adult influenza immunization rates in Puerto Rico. In order to inform public health actions to increase vaccination rates, we surveyed adults in Puerto Rico regarding influenza vaccination-related attitudes and barriers. METHODS: A random-digit-dialing telephone survey (50% landline: 50% cellphone) regarding influenza vaccination, attitudes, practices and barriers was conducted November 19-25, 2013 among adults in Puerto Rico. Survey results were weighted to reflect sampling design and adjustments for non-response. RESULTS: Among 439 surveyed, 229 completed the survey with a 52% response rate. Respondents' median age was 55 years; 18% reported receiving 2013-2014 influenza vaccination. Among 180 unvaccinated respondents, 38% reported barriers associated with limited access to vaccination, 24% reported they did not want or need influenza vaccination, and 20% reported safety concerns. Vaccinated respondents were more likely to know if they were recommended for influenza vaccination, to report greater perceived risk of influenza illness, and to report being less concerned about influenza vaccine safety (p-value<0.05). Of the 175 respondents who saw a healthcare provider (HCP) since July 1, 2013, 38% reported their HCP recommended influenza vaccination and 17% were offered vaccination. Vaccination rates were higher among adults who received a recommendation and/or offer of influenza vaccination (43% vs. 14%; p value<0.01). CONCLUSIONS: Failure of HCP to recommend and/or offer influenza vaccination and patient attitudes (low perceived risk of influenza virus infection) may have contributed to low vaccination rates during the 2013-2014 season. HCP and public health practitioners should strongly recommend influenza vaccination and provide vaccinations during clinical encounters or refer patients for vaccination. PMID- 26144898 TI - A versatile in vitro ELISA test for quantification and quality testing of infectious, inactivated and formulated rabies virus used in veterinary monovalent or combination vaccine. AB - Regulatory potency test for rabies vaccines requires mice vaccination followed by challenge with a live virus via intracerebral route. An alternative in vitro test, consistent with the "3R's" (Reduce, Replace, Refine) was designed to quantify active glycoprotein G using seroneutralizing monoclonal antibodies. This versatile ELISA targets well conformed neutralizing epitopes. Therefore, it quantifies only the trimeric pre-fusion form of glycoprotein G known to elicits the production of viral neutralizing antibodies. The ELISA makes it possible to quantify the rabies antigen during all steps of the product cycle (i.e. viral cultivation, downstream process, formulation and product stability in the presence of aluminum gel or other vaccine valence). Moreover, the batch-to-batch consistency of our active ingredients and formulated products could be demonstrated. PMID- 26144899 TI - A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection. AB - Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNgamma levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries. PMID- 26144900 TI - Preclinical development of a dengue tetravalent recombinant subunit vaccine: Immunogenicity and protective efficacy in nonhuman primates. AB - We describe here the preclinical development of a dengue vaccine composed of recombinant subunit carboxy-truncated envelope (E) proteins (DEN-80E) for each of the four dengue serotypes. Immunogenicity and protective efficacy studies in Rhesus monkeys were conducted to evaluate monovalent and tetravalent DEN-80E vaccines formulated with ISCOMATRIXTM adjuvant. Three different doses and two dosing regimens (0, 1, 2 months and 0, 1, 2, and 6 months) were evaluated in these studies. We first evaluated monomeric (DEN4-80E) and dimeric (DEN4-80EZip) versions of DEN4-80E, the latter generated in an attempt to improve immunogenicity. The two antigens, evaluated at 6, 20 and 100 MUg/dose formulated with ISCOMATRIXTM adjuvant, were equally immunogenic. A group immunized with 20 MUg DEN4-80E and AlhydrogelTM induced much weaker responses. When challenged with wild-type dengue type 4 virus, all animals in the 6 and 20 MUg groups and all but one in the DEN4-80EZip 100 MUg group were protected from viremia. Two out of three monkeys in the AlhydrogelTM group had breakthrough viremia. A similar study was conducted to evaluate tetravalent formulations at low (3, 3, 3, 6 MUg of DEN1 80E, DEN2-80E, DEN3-80E and DEN4-80E respectively), medium (10, 10, 10, 20 MUg) and high (50, 50, 50, 100 MUg) doses. All doses were comparably immunogenic and induced high titer, balanced neutralizing antibodies against all four DENV. Upon challenge with the four wild-type DENV, all animals in the low and medium dose groups were protected against viremia while two animals in the high-dose group exhibited breakthrough viremia. Our studies also indicated that a 0, 1, 2 and 6 month vaccination schedule is superior to the 0, 1, and 2 month schedule in terms of durability. Overall, the subunit vaccine was demonstrated to induce strong neutralization titers resulting in protection against viremia following challenge even 8-12 months after the last vaccine dose. PMID- 26144901 TI - Immunogenicity and safety of the 9-valent HPV vaccine in men. AB - OBJECTIVES: This study was designed to evaluate the immunogenicity and tolerability of a prophylactic 9-valent HPV (types 6/11/16/18/31/33/45/52/58) VLP (9vHPV) vaccine in young men 16-26 years of age in comparison to young women 16 26 years of age (the population that was used to establish 9vHPV vaccine efficacy). Safety and immunogenicity data from this study will be used to bridge 9vHPV vaccine efficacy findings in 16-26 year old women to 16-26 year old men. METHODS: This study enrolled 1106 heterosexual men (HM) and 1101 women who had not yet received HPV vaccination. In addition, 313 men having sex with men (MSM) were enrolled and were evaluated separately for immunogenicity because previous results showed that antibody responses to quadrivalent HPV (types 6/11/16/18) VLP (qHPV) vaccine were lower in MSM than in HM. All subjects were administered a 3 dose regimen (Day 1, Month 2, Month 6) of 9vHPV vaccine. Serum samples were collected for anti-HPV assays. Safety information was collected for ~ 12 months. RESULTS: The geometric mean titers (GMTs) for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 for HM were non-inferior to those of women at Month 7. For all vaccine HPV types, Month 7 GMTs were numerically lower in MSM than in HM. Over 99.5% of subjects were seropositive at Month 7 for each vaccine HPV type. Administration of 9vHPV vaccine to both 16-26 year old men and women was generally well tolerated. CONCLUSIONS: These results support bridging the efficacy findings with 9vHPV vaccine in young women 16-26 years of age to men 16 26 years of age. PMID- 26144902 TI - Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers. AB - An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as pneumococcal capsular polysaccharide vaccine and some publications also suggest a possible immunotolerance after revaccination with Vi-capsular polysaccharide vaccines. In this study, post-immunisation antibody concentrations in adult travellers first vaccinated with a Salmonella typhi Vi-capsular polysaccharide vaccine (primary vaccination group) were compared with those having received one or more vaccinations previously (multiple vaccinations group). Vaccines administered were Typherix((r)) (GlaxoSmithKline), Typhim Vi((r)) (Sanofi Pasteur MSD) or Hepatyrix((r)) (GlaxoSmithKline). Blood samples were obtained prior to vaccination (day 0) and on day 28 (-1/+14) after vaccination. Serum Vi-Antigen IgG concentrations were measured by ELISA. Of the 85 subjects included in the per protocol data set, 45 (53%) belonged to the multiple vaccinations group. In both groups, geometric mean antibody concentrations (GMCs) were significantly higher after vaccination than before vaccination. Pre-vaccination GMCs were lower in the primary vaccination group than in the multiple vaccinations group (3.40 MUg/ml versus 6.13 MUg/ml, P=0.005), while there was no significant difference in the post vaccination GMCs between groups (11.34 MUg/ml versus 14.58 MUg/ml, P=0.4). In the multiple vaccinations group, vaccination was performed 18 to 57 months after the last vaccination (median 38 months) and there was a negative correlation between time since last vaccination and antibody concentration on day 0. In conclusion, we were not able to demonstrate a relevant immunotolerance after multiple versus primary vaccination with S. typhi Vi-capsular polysaccharide vaccines. PMID- 26144903 TI - Long-lasting hyporesponsivenss induced by the 23-valent pneumococcal polysaccharide vaccine (PPV23) in asplenic patients with beta-thalassemia major. AB - We have previously shown that multiple vaccinations with 23-valent pneumococcal polysaccharide vaccine (PPV23s) resulted in attenuated antibody responses to subsequent 7-valent conjugate vaccine (PCV7) in asplenic adults with beta thalassemia major (Orthopoulos et al. Vaccine 2009; 27:350). However, there is evidence that PPV23-induced immune hyporesponsiveness could be overcome with time (Papadatou et al. Clin Infect Dis 2014; 59:862). In the current study we investigate the duration of hyporesponsiveness in the same cohort seven years after the original study vaccinations. Patients received one dose of 13-valent conjugate vaccine (PCV13) and antibody levels were measured before and one month after vaccination. Antibodies increased significantly after vaccination with PCV13, but were lower than post-PCV7 seven years earlier. Lower pre-vaccination antibody levels were associated with more robust response to PCV13. Our findings suggest that PPV23 should be used cautiously in asplenic adults vaccinated with multiple PPV23s in the past. Measurement of anti-pneumococcal antibodies before and after vaccination could be used to optimise timing of vaccinations and certify vaccine immunogenicity in such individuals. PMID- 26144904 TI - Attitudes and perceptions among the pediatric health care providers toward influenza vaccination in Qatar: A cross-sectional study. AB - BACKGROUND: Influenza is a communicable but preventable viral illness. Despite safe and effective vaccine availability, compliance rates are globally low. Neither local data on percentage of vaccination nor reasons for poor compliance among pediatric health providers are available in Qatar. AIM: To estimate the percentage of vaccinated health care providers at pediatrics department and know their perception and attitudes toward influenza vaccinations. METHODS: Cross sectional survey, conducted on 300 pediatrics healthcare professionals from January through April 2013 at the main tertiary teaching hospital in Qatar, included details of demographics, frequency, perceptions and suggestive ways to improve the compliance. FINDING: From among 230 respondents, 90 physicians and 133 allied health care professionals participated in this survey. Our study showed that percentages of participants who received flu vaccination were 67.7% and those who did not receive vaccination were 32.3%. Allied HCPs (69%) are more likely to get the vaccine compared to the physicians (66%). flu vaccination was approximately 5 times likely to be higher in the age group more than 40 years (P=0.002) compared to age less than or equals 40 years. Overall 70% healthcare providers were willing to recommend immunization to colleagues and patients compared to 30%, who were not willing. The reasons for noncompliance included fear of side effects, contracting the flu, vaccine safety and lack of awareness about the effectiveness. In order to promote immunization, participants believe that use of evidence-based statement, participating in an educational campaign, provides no cost/on site campaigns and leadership support is the most practical interventions. CONCLUSIONS: In the present study, the vaccine coverage among pediatrics HCPs seems higher than previously reported rates. Despite their positive attitude toward influenza vaccination, low acceptance and misconceptions of seasonal influenza vaccination by pediatric HCPs may have a negative effect on the successful immunization delivery and children immunization rate. Our findings would be useful for designing and implementing educational programs targeted to improve vaccination coverage rates. PMID- 26144905 TI - WITHDRAWN: Rh genotypes among Malaysian blood donors. AB - This article has been withdrawn at the request of the author and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26144906 TI - Delayed treatment of unstable proximal interphalangeal joint fracture dislocations with a dynamic external fixator. AB - BACKGROUND: Fracture-dislocations of the proximal interphalangeal joint (PIPJ) remain a challenging problem to treat. Although there are a number of papers describing the use of dynamic external fixators and force couples for treatment of unstable PIPJ fracture-dislocations acutely, the literature is scarce on delayed treatment of PIPJ fracture-dislocations, where malunion of the articular surface may theoretically compromise postoperative range of motion (ROM) at the PIPJ. The purpose of this study was to evaluate the effectiveness of dynamic distraction external fixation (DDEF) for the delayed treatment of PIPJ fracture dislocations at least 3 weeks after the inciting injury. METHODS: Ten consecutive patients were treated with delayed DDEF between 2010 and 2013. Postoperative ROM at the PIPJ was measured. Disabilities of the Arm, Shoulder and Hand (DASH) score and Michigan Hand Outcomes Questionnaire were administered to all patients postoperatively. RESULTS: Mean time from injury to surgery was 27.5 days. The mean follow-up period was 23.7 months (range 10-36). The mean active ROM at the PIPJ on final postoperative follow-up was 83.9 degrees (range 52-100). None of the patients experienced pin-tract infections. Mean DASH score was 3.7+3.4 and mean Michigan Hand Outcomes Questionnaire score was 97.3+3.0. All patients returned to work and resumed normal activities. CONCLUSIONS: Delayed treatment of unstable PIPJ fracture-dislocations with a DDEF is effective in restoring function to the PIPJ. Nascent malunion of the PIPJ articular surface does not compromise postoperative outcomes and the joint surface undergoes remodelling over time to restore a smooth and functional articular surface. PMID- 26144907 TI - More DATA to guide sequential osteoporosis therapy. PMID- 26144909 TI - Effect of crowding on several stages of protein aggregation in test systems in the presence of alpha-crystallin. AB - Macromolecular crowding can facilitate protein-protein interactions in the cell, in particular aggregation processes. To characterize the anti-aggregation activity of chaperones under conditions mimicking the crowded environment in the cell, two basic test systems are used. Test systems of the first type are based on aggregation of target proteins undergoing unfolding under different factors. Dithithreitol-induced aggregation of alpha-lactalbumin is used as such a system. The increase in the duration of lag phase after the addition of the crowder (polyethylene glycol; PEG) to the system containing alpha-crystallin has been interpreted as a retardation of the stages that are the rate-limiting stages of the general process of aggregation (the nucleation stage and the stages of clusterization of nuclei). Test systems of the second type are based on aggregation of UV-irradiated proteins. Such test systems permit investigating the effects of different agents directly on the stages of aggregation of unfolded protein. UV-irradiated glycogen phosphorylase b (Phb) is used as a target protein. Analysis of the initial rate of aggregation after the addition of PEG at different points in time to the mixture of UV-irradiated Phb and alpha-crystallin allowed estimating the time of half-conversion for the structural rearrangement of the primary UV-irradiated Phb-alpha-crystallin complex. PMID- 26144908 TI - Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA Switch study): extension of a randomised controlled trial. AB - BACKGROUND: Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies. The DATA study showed that combined teriparatide and denosumab increased bone mineral density more than either drug alone. Discontinuing teriparatide and denosumab, however, results in rapidly declining bone mineral density. In this DATA-Switch study, we aimed to assess the changes in bone mineral density in postmenopausal osteoporotic women who transitioned between treatments. METHODS: This randomised controlled trial (DATA-Switch) is a preplanned extension of the denosumab and teriparatide administration study (DATA), in which 94 postmenopausal osteoporotic women were randomly assigned to receive 24 months of teriparatide (20 mg daily), denosumab (60 mg every 6 months), or both drugs. In DATA-Switch, women originally assigned to teriparatide received denosumab (teriparatide to denosumab group), those originally assigned to denosumab received teriparatide (denosumab to teriparatide group), and those originally assigned to both received an additional 24 months of denosumab alone (combination to denosumab group). Bone mineral density at the spine, hip, and wrist were measured 6 months, 12 months, 18 months, and 24 months after the drug transitions as were biochemical markers of bone turnover. The primary endpoint was the percent change in posterior-anterior spine bone mineral density over 4 years. Between-group changes were assessed by one-way analysis of variance in our modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00926380. FINDINGS: Between Sept 27, 2011, and Jan 28, 2013, eligible women from the DATA study were enrolled into DATA-Switch. Of 83 potential enrollees from the DATA study, 77 completed at least one post baseline visit. After 48 months, the primary outcome of mean spine bone mineral density increased by 18.3% (95% CI 14.9-21.8) in 27 women in the teriparatide to denosumab group, 14.0% (10.9-17.2) in 27 women the denosumab to teriparatide group, and 16.0% (14.0-18.0) in 23 women in the combination to denosumab group, although this increase did not differ significantly between groups (for between group comparisons, p=0.13 for the teriparatide to denosumab group vs the denosumab to teriparatide group, p=0.30 for the teriparatide to denosumab group vs the combination to denosumab group, and p=0.41 for the denosumab to teriparatide group vs the combination to denosumab group). For the bone mineral density secondary outcomes, total hip bone mineral density increased more in the teriparatide to denosumab group (6.6% [95% CI 5.3-7.9]) than in the denosumab to teriparatide group (2.8% [1.3-4.2], p=0.0002), but had the greatest increase in the combination to denosumab group (8.6% [7.1-10.0]; p=0.0446 vs the teriparatide to denosumab group, p<0.0001 vs the denosumab to teriparatide group). Similarly, femoral neck bone mineral density increased more in the teriparatide to denosumab group (8.3% [95% CI 6.1-10.5]) and the combination to denosumab group (9.1% [6.1 12.0]) than in the denosumab to teriparatide group (4.9% [2.2-7.5]; p=0.0447 for teriparatide to denosumab vs denosumab to teriparatide, p=0.0336 for combination to denosumab vs denosumab to teriparatide). Differences between the combination to denosumab group and the teriparatide to denosumab group did not differ significantly (p=0.67). After 48 months, radius bone mineral density was unchanged in the teriparatide to denosumab group (0.0% [95% CI -1.3 to 1.4]), whereas it decreased by -1.8% (-5.0 to 1.3) in the denosumab to teriparatide group, and increased by 2.8% (1.2-4.4) in the combination to denosumab group (p=0.0075 for the teriparatide to denosumab group vs the combination to denosumab group; p=0.0099 for the denosumab to teriparatide group vs the combination to denosumab group). One participant in the denosumab to teriparatide group had nephrolithiasis, classified as being possibly related to treatment. INTERPRETATION: In postmenopausal osteoporotic women switching from teriparatide to denosumab, bone mineral density continued to increase, whereas switching from denosumab to teriparatide results in progressive or transient bone loss. These results should be considered when choosing the initial and subsequent management of postmenopausal osteoporotic patients. FUNDING: Amgen, Eli Lilly, and National Institutes of Health. PMID- 26144910 TI - Collagen based polyurethanes-A review of recent advances and perspective. AB - Collagen is mostly found in fibrous tissues such as tendons, ligaments and skin. Collagen makes up approximately 30% of the proteins within the body. These are tough and strong structures found all over the body: in bones, tendons and ligaments. Collagen being the most abundant protein provides tensile strength via cell matrix interactions to tissue architecture. Biomimetic materials of collagen origin gained wide spread acceptance in clinical applications. Vitamin C deficiency causes scurvy a serious and painful disease in which defective collagen prevents the formation of strong connective tissue, gums deteriorate and bleed, with loss of teeth; skin discolors, and wounds do not heal. Effective collagens prevent the manifestation of such disorders. Polyurethanes on the other hand are frequently used for various applications as they offered in wide-ranging of compositions, properties and complex structures. Collagen/PU bio-composites have potential array for biomedical applications. Considering versatile properties of the elongated fibrils and wide industrial and biomedical applications including biocompatibility of polyurethane, this review shed a light on collagen based polyurethane materials with their potential applications especially focusing the bio-medical field. PMID- 26144911 TI - Prevalence and descriptive analysis of congenital heart disease in parturients: obstetric, neonatal, and anesthetic outcomes. AB - STUDY OBJECTIVE: The study objectives are to (1) assess prevalence of congenital heart disease (CHD), (2) describe outcomes of pregnancies in women with CHD, (3) compare outcomes in women with and without CHD, and (4) characterize neonatal outcomes in pregnancies complicated by CHD. DESIGN: This was a retrospective cohort study of women who delivered at the University of Colorado Hospital. Diagnosis of CHD was identified based on history of cardiac disease, pulmonary disease, or subacute bacterial endocarditis prophylaxis during labor and confirmed with echocardiogram when available. Comprehensive retrospective review of anesthetic, obstetric, and neonatal outcomes was performed. SETTING: University of Colorado Hospital. PATIENTS: 18,226 women. INTERVENTIONS: Medical record review. MEASUREMENTS: Valvular abnormalities, New York Heart Failure Association classification scores, types of CHD, maternal age, race, gravidity, parity, maternal prepregnancy body mass index, cigarette use, type of delivery, type of analgesia used, early initiation of neuraxial analgesia, arrhythmias, need for peripartum diuretics, prolonged maternal hospital stay, preterm birth, small for gestational age, neonatal CHD, neonatal or maternal intensive care unit (ICU) admissions, and maternal or neonatal death. MAIN RESULTS: We identified 117 pregnancies in 110 women with CHD. Parturients with CHD were more likely to have operative vaginal delivery (P < .0001), neonatal ICU admissions (P = .003), and had prolonged hospital stays. Occurrence of CHD in neonates was 6%. Moderate-to severe valvular disease was associated with increased rates of operative vaginal delivery, early initiation of neuraxial labor analgesia, cardiac complications (including arrhythmia and use of diuretics), prolonged hospital stay, and maternal ICU admission. However, most deliveries and births were uncomplicated; and there were one case each of maternal mortality and fetal death after birth. CONCLUSION: Operative abdominal deliveries and neonatal ICU admissions are more common in women with CHD, but these pregnancies are generally well tolerated with low mortality rates. PMID- 26144912 TI - Ultrasound-guided transversus thoracic muscle plane block: a cadaveric study of the spread of injectate. PMID- 26144913 TI - Respiratory gas exchange during robotic-assisted laparoscopic radical prostatectomy. AB - STUDY OBJECTIVE: Robotic-assisted laparoscopic prostatectomy requires patients to be secured in a steep Trendelenburg position for several hours. Added to the CO2 pneumoperitoneum that is created, this positioning invariably restricts diaphragmatic and chest wall excursion, which can adversely affect respiratory gas exchange. This study sought to measure the extent of respiratory gas change during this procedure. DESIGN: Retrospective, institutional review board approved. SETTING: Operating room. PATIENTS: N = 186 males, American Society of Anesthesiologists 2-3, with prostatic carcinoma undergoing robotic-assisted laparoscopic radical prostatectomy. INTERVENTIONS: Arterial blood gases and noninvasive respiratory measurements were recorded for those patients (n = 32) in whom a radial arterial catheter had been inserted intraoperatively, specifically timed to different phases of the procedure: supine lithotomy, steep Trendelenburg, and return to supine. Ventilatory parameters were standardized. MEASUREMENTS: Systemic blood pressure, heart rate, respiratory rate, Pao2, Paco2, oxygen saturation as measured by pulse oximetry, and end-tidal carbon dioxide pressure. MAIN RESULTS: Although no patients developed perioperative respiratory complications, the Pao2 invariably fell (395 vs 316 mm Hg; P = .001) while the patients were in steep Trendelenburg, and the Paco2-end-tidal carbon dioxide pressure rose (10.0 vs 13.4 mm Hg; P < .0001). Upon return to supine, patients' respiratory measurements promptly returned to within 15% of baseline. Subgroup analysis for high-BMI vs low-BMI patients as well as for patients with pulmonary disease and/or a smoking history showed similar individual effects and only small, although significant, respiratory gas exchange aberrations. CONCLUSIONS: Positioning patients with a CO2 pneumoperitoneum in steep Trendelenburg for several hours imposes restriction of diaphragmatic and chest wall movement sufficient for respiratory gas exchange to be adversely affected. Return of function to within 15% of baseline occurred within minutes after return to supine and release of the CO2 pneumoperitoneum. No patients during the study period developed pulmonary complications that required alteration in their level of care. PMID- 26144914 TI - The video monitor with 2 input monitors is a useful video monitor in the intubation of a double-lumen tube. PMID- 26144934 TI - Disruption of Circadian Rhythms and Sleep in Critical Illness: Potential Implications for Angiogenesis After Myocardial Infarction. A Review. AB - Angiogenesis plays an important role in the treatment of acute myocardial infarction (MI). Formation of micro-vessels has the potential to prevent apoptosis of the ischemic myocardium and to improve cardiac function after MI. Delivery of growth factors or administration of stem/progenitor cells (mainly from bone marrow) are the dominant therapies to induce angiogenesis after MI. Nevertheless, clinical trials have shown that delivery of a single growth factor or single type of cell does not provide sufficient angiogenesis to promote cardiac repair. Circadian rhythms control many physiological and pathological processes in mammals. Many studies show a close relationship between circadian rhythms and MI. Disruption of the circadian rhythms in humans leads to increased incidence of MI. The onset and infarct area of MI are markedly elevated at certain time points. Determining the mechanisms of angiogenesis and vessel maturation in the ischemic heart under the control of circadian rhythms could help in the development of novel and angiogenesis- targeted therapeutics for the treatment of MI. PMID- 26144935 TI - Entrainment of the Human Circadian Clock to the Light-Dark Cycle and its Impact on Patients in the ICU and Nursing Home Settings. AB - A robust circadian timekeeping system is important for human health and well being. Inappropriately timed light exposure can cause circadian and sleep disruption, which has been shown to have negative health consequences. Lighting in medical care facilities, such as the NICU, ICU, and nursing homes, is not typically controlled and may be associated with circadian disruption observed in such settings. Cycled lighting and increased exposure to sunlight in medical care facilities have been shown to have positive effects on patient recovery and well being, and expedite hospital discharge. Additional clinical research is needed to determine the optimal light exposure timing, duration, intensity, and spectrum to best promote recovery, health and well-being in the context of medical care. PMID- 26144936 TI - On the Relationship Between the Light/Dark Cycle, Melatonin and Oxidative Stress. AB - The adaptation of species to the environment in which they live is accomplished by so-called "clocks" that allow the biological, physiological, metabolic and behavioral system to correct any development during the day. The alteration of those 'clocks' (circadian rhythms) shows a strong relationship with organic disorders such as neurodegenerative diseases. Many studies show that oxidative stress combined with pro-inflammatory mechanisms, play a key role in the development of neurodegenerative diseases and psychiatric disorders. Oxidative stress is fought by many antioxidant molecules. Melatonin, a hallmark of circadian rhythm functionality, is a natural antioxidant with a circadian secretion pattern. The mechanisms involved in the antioxidant properties of melatonin are complex but its depletion or lack unequivocally leads to cell damage. This process is also linked to the disruption of the circadian rhythm. A disrupted circadian rhythm followed by oxidative stress and inflammatory processes could be the pathophysiological basis for several disorders of the central nervous system. In the current review we will analyze those interactions. We will focus on the relationship between melatonin and its light/dark rhythms of secretion and how the antioxidant properties of melatonin opens a new therapeutic hope against central nervous system disorders. PMID- 26144937 TI - Disruption of Circadian Rhythms and Sleep in Critical Illness and its Impact on the Development of Delirium. AB - PURPOSE: This article reviews our current understanding of the relationships between critical illness, circadian disruption, and delirium. SUMMARY: Delirium is a common and morbid complication of hospitalization, particularly in the setting of critical illness and intensive care unit (ICU) admission. Critical illness involves a host of acute metabolic, hormonal and inflammatory responses that appear to disrupt normal sleep architecture and precipitate cerebral dysfunction. The intervention-heavy environment of the ICU further disrupts normal circadian rhythms and increases delirium risk. Despite strong evidence for correlation of sleep disruption, critical illness and delirium, causal relationships remain difficult to prove. Delirium is almost certainly a multifactorial condition. This article reviews proposed pathophysiologic mechanisms and potential therapeutic targets. In the absence of definitive pharmacologic therapy, interventions prioritizing maintenance of normal circadian, sleep, and behavioral patterns have shown promise in delirium risk reduction. PMID- 26144938 TI - Obstructive Sleep Apnea and Cardiovascular Disease - A New Target for Treatment. AB - Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial (hypopnea) or complete interruption (apnea) in breathing during sleep due to airway collapse in the oral or pharyngeal region. Prospective studies have established the adverse cardiovascular consequences of OSA, including an increased risk for developing hypertension, coronary artery disease, stroke, and heart failure. However, more studies are needed to better assess the impact of OSA, and possible benefit of treatment with continuous positive airway pressure (CPAP) on cardiovascular mortality. The leading pathophysiological mechanisms involved in the changes triggered by OSA include intermittent hypoxemia and re oxygenation, arousals and changes in intrathoracic pressure. Hypertension is strongly related with activation of the sympathetic nervous system, stimulation of the renin-angiotensin-aldosterone system and endothelial dysfunction. OSA should be suspected in hypertensive individuals, particularly in patients with resistant hypertension. CPAP treatment reduces blood pressure, and its effects are more pronounced in patients with high baseline blood pressure and elevated treatment compliance. At present, no clear evidence supports CPAP treatment for primary or secondary cardiovascular disease prevention. PMID- 26144939 TI - Humans Entrain to Sunlight - Impact of Social Jet Lag on Disease and Implications for Critical Illness. AB - The circadian clock is a biological system that allows organisms to adapt to temporal constraints of the environment. It governs all body functions. The circadian clock has an endogenous period and entrains to the external day by the means of timing cues, also called "zeitgebers". A discrepancy between internal and external day or internal day and certain body functions results in circadian desynchrony, most prominently represented in jet lag. Circadian desynchrony may be a factor in many diseases. This review presents literature in which the impact of circadian desynchrony on disease development - with a special focus on critical illness - has been addressed. The treatment options that have so far been investigated are also presented. PMID- 26144940 TI - Disruption of Circadian Rhythms and Sleep on Critical Illness and the Impact on Cardiovascular Events. AB - The cardiovascular system exhibits significant daily rhythms in physiologic processes (heart rate, blood pressure, cardiac contractility and function), and molecular gene and protein expression. An increasing number of clinical and experimental studies demonstrate the circadian system is an important underlying mechanism that coordinates these rhythmic processes for the health of the cardiovascular system. However, what happens when rhythms are disturbed has been generally clinically unappreciated. Here we describe the profound adverse impact of disturbed circadian rhythms and sleep on the cardiovascular system, including recovery from myocardial infarction in acute care settings, shift work and heart disease, sleep disorders including obstructive sleep apnea, and cardiovascular pathophysiology associated with disturbed nocturnal blood pressure profiles. We also discuss therapeutic applications of circadian rhythms for the cardiovascular system. Cardiovascular disease is a leading cause of death worldwide, and applying circadian biology to cardiology (and indeed medicine in general) provides a new translational approach to benefit patients clinically. PMID- 26144941 TI - Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light Dark Contrast and Melatonin Therapy in an ICU Environment. AB - The confinement of critically ill patients in intensive care units (ICU) imposes environmental constancy throughout both day and night (continuous light, noise, caring activities medications, etc.), which has a negative impact on human health by inducing a new syndrome known as circadian misalignment, circadian disruption or chronodisruption (CD). This syndrome contributes to poor sleep quality and delirium, and may impair septic states frequently observed in critically ill patients. However, and although the bidirectional crosstalk between CD with sleep impairment, delirium and inflammation in animal models has been known for years and has been suspected in ICU patients, few changes have been introduced in the environment and management of ICU patients to improve their circadian rhythmicity. Delirium, the most serious condition because it has a severe effect on prognosis and increases mortality, as well as sleep impairment and sepsis, all three of them linked to disorganization of the circadian system in critically ill patients, will be revised considering the functional organization of the circadian system, the main input and output signals that synchronize the clock, including a brief description of the molecular circadian clock machinery, the non visual effects of light, and the ICU light environment. Finally, the potential usefulness of increased light/dark contrast and melatonin treatment in this context will be analyzed, including some practical countermeasures to minimize circadian disruption and improve circadian system chronoenhancement, helping to make these units optimal healing environments for patients. PMID- 26144942 TI - Disruption of Circadian Rhythms in Critical Illness - A Role of Hyperoxia-Induced Lung Injury. AB - With the current high rates of associated morbidity and mortality, proper management of critical illness is vital in the treatment of severely ill patients. Disruptions of key body systems stemming from these illnesses may be attributed to their severity and limited treatment options. Disruption in circadian rhythms caused by critical illnesses may lead to a decreased patient prognosis, as the biological clocks stemming from circadian rhythms play several key roles in regulating our internal pathways. This review will highlight how the occurrence of hyperoxic injury during the progression of critical illness may severely damage circadian rhymicity, and lead to an increased risk of infection, development of disease, severity of symptoms, morbidity and mortality, and dysregulation of multiple body systems. Overall, there is strong evidence suggesting that the disruption of circadian rhythms may be caused by critical illness. Studies performed on several animal models have shown alterations of key genes associated with circadian clock function may heavily contribute to the increased severity of critical illness linked to circadian disruption. This review will aid in further understanding the link between circadian disruption and critical illness. PMID- 26144943 TI - Disruption of Circadian Rhythms and Sleep in Critical Illness and its Impact on Innate Immunity. AB - The earth rotates on its axis around the sun, creating a day and night cycle, that caused the development of circadian rhythms. The circadian rhythm is primarily entrained by light, which is detected by the retina. Retinal ganglion cells project to a part of the hypothalamus termed suprachiasmatic nucleus. Here, we find the master molecular clock, composed of a transcription-translation-loop at its core. The master clock indirectly influences the innate immune system via different biological systems. Also, the master clock controls the peripheral clocks, which are present in innate immune cells. Here, circadian rhythm proteins influence the response of immune cells to pathogens. Furthermore, the master clock influences our sleep-pattern, the most important restorative physiological function. In critically ill patients the circadian rhythm is substantially altered, supporting a dysfunctional innate immune response. This review discusses recent basic science findings on the interaction of the circadian rhythm and the innate immune system. Furthermore we give an outlook on potential future therapeutic strategies. PMID- 26144944 TI - The Role of Circadian Rhythms in Fatal Arrhythmias and the Potential Impact of Intervention for Sleep-Disordered Breathing. AB - There exist circadian patterns in the occurrence of sudden cardiac death. The suprachiasmatic nuclei is the 'master clock' in mammalian bodies. Furthermore, several circadian genes have been successfully isolated in basic studies and a huge variety of key players form the human circadian rhythm. Obvious circadian patterns are present in the occurrence of critical events, but those characteristics differ greatly according to each disease. In this review we summarized the current understanding of the basic mechanism and association with specific cardiovascular diseases that demonstrate a circadian onset of fatal events. We also summarized the recent deep understanding of sleep-disordered breathing. The close relationship between sleep-disordered breathing and cardiovascular diseases may provide us with the possibility of a novel intervention against sudden cardiac death. PMID- 26144945 TI - A differential equation for the asymptotic fitness distribution in the Bak Sneppen model with five species. AB - The Bak-Sneppen model is an abstract representation of a biological system that evolves according to the Darwinian principles of random mutation and selection. The species in the system are characterized by a numerical fitness value between zero and one. We show that in the case of five species the steady-state fitness distribution can be obtained as a solution to a linear differential equation of order five with hypergeometric coefficients. Similar representations for the asymptotic fitness distribution in larger systems may help pave the way towards a resolution of the question of whether or not, in the limit of infinitely many species, the fitness is asymptotically uniformly distributed on the interval [fc, 1] with fc ? 2/3. PMID- 26144947 TI - [Carpe diem!]. PMID- 26144948 TI - [Preserving independent living]. PMID- 26144946 TI - Molecular diagnosis of coenzyme Q10 deficiency. AB - Coenzyme Q10 (CoQ) deficiency syndromes comprise a growing number of neurological and extraneurological disorders. Primary-genetic but also secondary CoQ deficiencies have been reported. The biochemical determination of CoQ is a good tool for the rapid identification of CoQ deficiencies but does not allow the selection of candidate genes for molecular diagnosis. Moreover, the metabolic pathway for CoQ synthesis is an intricate and not well-understood process, where a large number of genes are implicated. Thus, only next-generation sequencing techniques (either genetic panels of whole-exome and -genome sequencing) are at present appropriate for a rapid and realistic molecular diagnosis of these syndromes. The potential treatability of CoQ deficiency strongly supports the necessity of a rapid molecular characterization of patients, since primary CoQ deficiencies may respond well to CoQ treatment. PMID- 26144949 TI - [Home, the elderly person's identity card]. AB - Ageing at home is a cultural reality. Home carries an emotional weight, and even more so as we age. Furthermore, our home may be a protective envelope, a narcissistic image of ourselves and a territory to share. However, the perspective of new types of "home", better adapted to the elderly, is taking shape, as is the moving of boundaries between the institution and home. PMID- 26144950 TI - [Timing the discharge of the elderly patient]. AB - The discharge of an elderly hospitalised patient is envisaged as soon as they are admitted and even before they arrive. When a request to admit a patient is submitted to the admission commission, the patient's living conditions and routines are closely examined, as they determine the conditions for their discharge and therefore indirectly the timing of the decision to discharge them PMID- 26144951 TI - [The visit prior to returning home]. AB - Towards the end of a hospital stay, the question of the elderly person's future is raised. Depending on the situation, a return home, follow-up and rehabilitation care or admission to a nursing home may be envisaged. When a return home is considered, the preparatory home visit is important, both for the nursing team as well as for the patient and their family, as it enables the feasibility and suitability of the project to be assessed. Often coming down to an assessment regarding accessibility, it also makes the patient and their family think about the capacities of the hospitalised person and their future day-to-day reality. PMID- 26144952 TI - [A plan for improving patient discharge]. AB - A new discharge scheme has been put in place at Ambroise-Pare hospital. It fulfils several objectives. Coordination between the different hospital players has been strengthened and the patient's clinical pathway optimised. PMID- 26144953 TI - [Maintaining patients' autonomy at home]. AB - To maintain the flow of hospital discharges, the patient's return home with support from a home nursing service is important. If any difficulties are identified, there are various programmes or good practices which can be put into place. The future law on adapting society to ageing also comprises a scheme combining home assistance and nursing care. PMID- 26144954 TI - [Can a nursing home feel like home?]. AB - While one of the missions of a nursing home is the resident's medical care, it must also ensure that its approach focuses on the resident as a person. From the preadmission interview through to the furnishing of the person's own private space, the resident must be given the necessary support to enable them to view the nursing home as a home in its own right. PMID- 26144955 TI - [Assistance and care at home, the MobiQual Nutrition Domicile tool]. AB - The Nutrition Domicile tool was developed as part of the MobiQual programme which aims to improve the quality of professional practices in geriatric and gerontological institutions and at home. Its pedagogical content was drawn up by a multi-disciplinary and multi-professional taskforce, with the participation of the main federations from the home care sector. PMID- 26144956 TI - [The resilient elderly person]. AB - Ageing requires a time of adaptation necessary for a person's loved ones and the environment, as well as the ageing body. Changes are imposed which require a new psychological energy to counter the losses and sometimes the traumas. Communicating in order to create a certain amount of resilience is one of the challenges of geriatric psychiatry. PMID- 26144957 TI - [The specificities of care in cognitive-behavior units]. AB - Special units have been created within rehabilitation units to provide care to patients with productive behavior disorders, associated with Alzheimer's disease or other forms of dementia. They must respect organizational and architectural constraints and develop multiple partnerships. Based on an assessment and their expertise in behavior disorders, the multidisciplinary team draws up and implements a personalized care program comprising non pharmacological approaches, the benefit of which can usually be seen in the abatement of the disorders. Thorough preparation of the patient's return home or admission to a nursing home enables knowledge concerning the patient's specific situation to be passed on to other caregivers and the patient's family. PMID- 26144958 TI - [Diagnosis of a pancreatic neuroendocrine tumor in an 84 year old patient]. PMID- 26144959 TI - [Femoral neck fractures in the elderly]. PMID- 26144967 TI - Transformation from a retinal to a cyclopean representation in human visual cortex. AB - We experience our visual world as seen from a single viewpoint, even though our two eyes receive slightly different images. One role of the visual system is to combine the two retinal images into a single representation of the visual field, sometimes called the cyclopean image [1]. Conventional terminology, i.e. retinotopy, implies that the topographic organization of visual areas is maintained throughout visual cortex [2]. However, following the hypothesis that a transformation occurs from a representation of the two retinal images (retinotopy) to a representation of a single cyclopean image (cyclopotopy), we set out to identify the stage in visual processing at which this transformation occurs in the human brain. Using binocular stimuli, population receptive field mapping (pRF), and ultra-high-field (7 T) fMRI, we find that responses in striate cortex (V1) best reflect stimulus position in the two retinal images. In extrastriate cortex (from V2 to LO), on the other hand, responses better reflect stimulus position in the cyclopean image. These results pinpoint the location of the transformation from a retinal to a cyclopean representation and contribute to an understanding of the transition from sensory to perceptual stimulus space in the human brain. PMID- 26144968 TI - Dissociable Effects of Serotonin and Dopamine on the Valuation of Harm in Moral Decision Making. AB - An aversion to harming others is a core component of human morality and is disturbed in antisocial behavior. Deficient harm aversion may underlie instrumental and reactive aggression, which both feature in psychopathy. Past work has highlighted monoaminergic influences on aggression, but a mechanistic account of how monoamines regulate antisocial motives remains elusive. We previously observed that most people show a greater aversion to inflicting pain on others than themselves. Here, we investigated whether this hyperaltruistic disposition is susceptible to monoaminergic control. We observed dissociable effects of the serotonin reuptake inhibitor citalopram and the dopamine precursor levodopa on decisions to inflict pain on oneself and others for financial gain. Computational models of choice behavior showed that citalopram increased harm aversion for both self and others, while levodopa reduced hyperaltruism. The effects of citalopram were stronger than those of levodopa. Crucially, neither drug influenced the physical perception of pain or other components of choice such as motor impulsivity or loss aversion, suggesting a direct and specific influence of serotonin and dopamine on the valuation of harm. We also found evidence for dose dependency of these effects. Finally, the drugs had dissociable effects on response times, with citalopram enhancing behavioral inhibition and levodopa reducing slowing related to being responsible for another's fate. These distinct roles of serotonin and dopamine in modulating moral behavior have implications for potential treatments of social dysfunction that is a common feature as well as a risk factor for many psychiatric disorders. PMID- 26144969 TI - A Mechanistic Link between Olfaction and Autism Spectrum Disorder. AB - Internal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD). However, whether impaired IAMs occur across sensory systems and how they relate to the major phenotype of ASD, namely impaired social communication, remains unclear. Olfaction relies on an IAM known as the sniff response, where sniff magnitude is automatically modulated to account for odor valence. To test the failed IAM theory in olfaction, we precisely measured the non-verbal non-task-dependent sniff response concurrent with pleasant and unpleasant odors in 36 children--18 with ASD and 18 matched typically developing (TD) controls. We found that whereas TD children generated a typical adult-like sniff response within 305 ms of odor onset, ASD children had a profoundly altered sniff response, sniffing equally regardless of odor valance. This difference persisted despite equal reported odor perception and allowed for 81% correct ASD classification based on the sniff response alone (binomial, p < 0.001). Moreover, increasingly aberrant sniffing was associated with increasingly severe ASD (r = -0.75, p < 0.001), specifically with social (r = -0.72, p < 0.001), but not motor (r < -0.38, p > 0.18), impairment. These results uncover a novel ASD marker implying a mechanistic link between the underpinnings of olfaction and ASD and directly linking an impaired IAM with impaired social abilities. PMID- 26144970 TI - Three myosins contribute uniquely to the assembly and constriction of the fission yeast cytokinetic contractile ring. AB - Cytokinesis in fission yeast cells depends on conventional myosin-II (Myo2) to assemble and constrict a contractile ring of actin filaments. Less is known about the functions of an unconventional myosin-II (Myp2) and a myosin-V (Myo51) that are also present in the contractile ring. Myo2 appears in cytokinetic nodes around the equator 10 min before spindle pole body separation (cell-cycle time, 10 min) independent of actin filaments, followed by Myo51 at time zero and Myp2 at time +20 min, both located between nodes and dependent on actin filaments. We investigated the contributions of these three myosins to cytokinesis using a severely disabled mutation of the essential myosin-II heavy-chain gene (myo2-E1) and deletion mutations of the other myosin heavy-chain genes. Cells with only Myo2 assemble contractile rings normally. Cells with either Myp2 or Myo51 alone can assemble nodes and actin filaments into contractile rings but complete assembly later than normal. Both Myp2 and Myo2 contribute to constriction of fully assembled rings at rates 55% that of normal in cells relying on Myp2 alone and 25% that of normal in cells with Myo2 alone. Myo51 alone cannot constrict rings but increases the constriction rate by Myo2 in Deltamyp2 cells or Myp2 in myo2-E1 cells. Three myosins function in a hierarchal, complementary manner to accomplish cytokinesis, with Myo2 and Myo51 taking the lead during contractile ring assembly and Myp2 making the greatest contribution to constriction. PMID- 26144971 TI - Iron-Starvation-Induced Mitophagy Mediates Lifespan Extension upon Mitochondrial Stress in C. elegans. AB - Frataxin is a nuclear-encoded mitochondrial protein involved in the biogenesis of Fe-S-cluster-containing proteins and consequently in the functionality of the mitochondrial respiratory chain. Similar to other proteins that regulate mitochondrial respiration, severe frataxin deficiency leads to pathology in humans--Friedreich's ataxia, a life-threatening neurodegenerative disorder--and to developmental arrest in the nematode C. elegans. Interestingly, partial frataxin depletion extends C. elegans lifespan, and a similar anti-aging effect is prompted by reduced expression of other mitochondrial regulatory proteins from yeast to mammals. The beneficial adaptive responses to mild mitochondrial stress are still largely unknown and, if characterized, may suggest novel potential targets for the treatment of human mitochondria-associated, age-related disorders. Here we identify mitochondrial autophagy as an evolutionarily conserved response to frataxin silencing, and show for the first time that, similar to mammals, mitophagy is activated in C. elegans in response to mitochondrial stress in a pdr-1/Parkin-, pink-1/Pink-, and dct-1/Bnip3-dependent manner. The induction of mitophagy is part of a hypoxia-like, iron starvation response triggered upon frataxin depletion and causally involved in animal lifespan extension. We also identify non-overlapping hif-1 upstream (HIF-1-prolyl hydroxylase) and downstream (globins) regulatory genes mediating lifespan extension upon frataxin and iron depletion. Our findings indicate that mitophagy induction is part of an adaptive iron starvation response induced as a protective mechanism against mitochondrial stress, thus suggesting novel potential therapeutic strategies for the treatment of mitochondrial-associated, age-related disorders. PMID- 26144973 TI - The materials science of collagen. AB - Collagen is the principal biopolymer in the extracellular matrix of both vertebrates and invertebrates. It is produced in specialized cells (fibroblasts) and extracted into the body by a series of intra and extracellular steps. It is prevalent in connective tissues, and the arrangement of collagen determines the mechanical response. In biomineralized materials, its fraction and spatial distribution provide the necessary toughness and anisotropy. We review the structure of collagen, with emphasis on its hierarchical arrangement, and present constitutive equations that describe its mechanical response, classified into three groups: hyperelastic macroscopic models based on strain energy in which strain energy functions are developed; macroscopic mathematical fits with a nonlinear constitutive response; structurally and physically based models where a constitutive equation of a linear elastic material is modified by geometric characteristics. Viscoelasticity is incorporated into the existing constitutive models and the effect of hydration is discussed. We illustrate the importance of collagen with descriptions of its organization and properties in skin, fish scales, and bone, focusing on the findings of our group. PMID- 26144972 TI - Antimicrobial Peptides: Insights into Membrane Permeabilization, Lipopolysaccharide Fragmentation and Application in Plant Disease Control. AB - The recent increase in multidrug resistance against bacterial infections has become a major concern to human health and global food security. Synthetic antimicrobial peptides (AMPs) have recently received substantial attention as potential alternatives to conventional antibiotics because of their potent broad spectrum antimicrobial activity. These peptides have also been implicated in plant disease control for replacing conventional treatment methods that are polluting and hazardous to the environment and to human health. Here, we report de novo design and antimicrobial studies of VG16, a 16-residue active fragment of Dengue virus fusion peptide. Our results reveal that VG16KRKP, a non-toxic and non-hemolytic analogue of VG16, shows significant antimicrobial activity against Gram-negative E. coli and plant pathogens X. oryzae and X. campestris, as well as against human fungal pathogens C. albicans and C. grubii. VG16KRKP is also capable of inhibiting bacterial disease progression in plants. The solution-NMR structure of VG16KRKP in lipopolysaccharide features a folded conformation with a centrally located turn-type structure stabilized by aromatic-aromatic packing interactions with extended N- and C-termini. The de novo design of VG16KRKP provides valuable insights into the development of more potent antibacterial and antiendotoxic peptides for the treatment of human and plant infections. PMID- 26144974 TI - Environment as 'Brain Training': A review of geographical and physical environmental influences on cognitive ageing. AB - Global ageing demographics coupled with increased urbanisation pose major challenges to the provision of optimal living environments for older persons, particularly in relation to cognitive health. Although animal studies emphasize the benefits of enriched environments for cognition, and brain training interventions have shown that maintaining or improving cognitive vitality in older age is possible, our knowledge of the characteristics of our physical environment which are protective for cognitive ageing is lacking. The present review analyses different environmental characteristics (e.g. urban vs. rural settings, presence of green) in relation to cognitive performance in ageing. Studies of direct and indirect associations between physical environment and cognitive performance are reviewed in order to describe the evidence that our living contexts constitute a measurable factor in determining cognitive ageing. PMID- 26144993 TI - Glutamic acid ameliorates estrogen deficiency-induced menopausal-like symptoms in ovariectomized mice. AB - Some amino acids are considered alternative therapies for improving menopausal symptoms. Glutamic acid (GA), which is abundant in meats, fish, and protein-rich plant foods, is known to be a neurotransmitter or precursor of gamma-aminobutyric acid. Although it is unclear if GA functions in menopausal symptoms, we hypothesized that GA would attenuate estrogen deficiency-induced menopausal symptoms. The objective to test our hypothesis was to examine an estrogenic effect of GA in ovariectomized (OVX) mice, estrogen receptor (ER)-positive human osteoblast-like MG-63 cells, and ER-positive human breast cancer MCF-7 cells. The results demonstrated that administration with GA to mice suppressed body weight gain and vaginal atrophy when compared with the OVX mice. A microcomputed tomographic analysis of the trabecular bone showed increases in bone mineral density, trabecular number, and connectivity density as well as a significant decrease in total porosity of the OVX mice treated with GA. In addition, GA increased serum levels of alkaline phosphatase and estrogen compared with the OVX mice. Furthermore, GA induced proliferation and increased ER-beta messenger RNA (mRNA) expression, estrogen response element (ERE) activity, extracellular signal regulated kinase phosphorylation, and alkaline phosphatase activity in MG-63 cells. In MCF-7 cells, GA also increased proliferation, Ki-67 mRNA expression, ER beta mRNA expression, and ERE activity. Estrogen response element activity increased by GA was inhibited by an estrogen antagonist. Taken together, our data demonstrated that GA has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells. PMID- 26144994 TI - Novel drug delivery systems for actinides (uranium and plutonium) decontamination agents. AB - The possibility of accidents in the nuclear industry or of nuclear terrorist attacks makes the development of new decontamination strategies crucial. Among radionuclides, actinides such as uranium and plutonium and their different isotopes are considered as the most dangerous contaminants, plutonium displaying mostly a radiological toxicity whereas uranium exhibits mainly a chemical toxicity. Contamination occurs through ingestion, skin or lung exposure with subsequent absorption and distribution of the radionuclides to different tissues where they induce damaging effects. Different chelating agents have been synthesized but their efficacy is limited by their low tissue specificity and high toxicity. For these reasons, several groups have developed smart delivery systems to increase the local concentration of the chelating agent or to improve its biodistribution. The aim of this review is to highlight these strategies. PMID- 26144995 TI - New strategies for local treatment of vaginal infections. AB - Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route. PMID- 26144996 TI - Raman spectroscopy for physiological investigations of tissues and cells. AB - Raman micro-spectroscopy provides a convenient non-destructive and location specific means of probing cellular physiology and tissue physiology at sub-micron length scales. By probing the vibrational signature of molecules and molecular groups, the distribution and metabolic products of small molecules that cannot be labeled with fluorescent dyes can be analyzed. This method works well for molecular concentrations in the micro-molar range and has been demonstrated as a valuable tool for monitoring drug-cell interactions. If the small molecule of interest does not contain groups that would allow for a discrimination against cytoplasmic background signals, "labeling" of the molecule by isotope substitution or by incorporating other unique small groups, e.g. alkynes provides a stable signal even for time-lapse imaging such compounds in living cells. In this review we highlight recent progress in assessing the physiology of cells and tissue by Raman spectroscopy and imaging. PMID- 26144997 TI - Noradrenaline modulates the presence of gonadotropin-releasing hormone in ovary. The importance of its interrelation on the ovarian steroidogenesis and apoptosis on dioestrus II in rat. AB - The aim of this work was to investigate if noradrenaline (NA), added in the coeliac ganglion -superior ovarian nerve- ovary system (CG-SON-O) and in ovary incubation, modifies the release of ovarian progesterone (P4), gonadotropin releasing hormone (GnRH) and oestradiol (E2), and the expression of 3beta-HSD and 20alpha-HSD and proapoptotic bax and antiapoptotic bcl-2 on dioestrus II in the rat. The CG-SON-O system and the ovary were removed and placed in one cuvette containing Krebs-Ringer solution (control groups), and NA was added to the ganglion compartment in the ex vivo system and in the ovary compartment in the ovary incubation (experimental groups). P4, GnRH and E2 were measured by RIA, and gene expression was measured by RT-PCR. In the ex-vivo system, the release of ovarian P4 and GnRH and the expression of 3beta-HSD and bax decreased; E2 and bcl 2 increased, and the bax/bcl-2 ratio decreased. However, in the ovary incubation, P4, GnRH, the expression of 3beta-HSD and bax increased; E2, the expression of 20alpha-HSD and bcl-2 decreased while the bax/bcl-2 ratio increased, thus favoring apoptosis. The peripheral nervous system protected the ovary from the apoptotic mechanisms while in the ovary incubation the effect was reverted. Our results indicate that NA regulates ovarian steroidogenesis and apoptosis by modulating GnRH release from the coeliac ganglion and ovary, being NA a possible generator of a GnRH-gonadotropins axis in the ovary. This work is expected to contribute with new evidence of the clinical importance of catecholamines and GnRH in therapy and prevention of ovarian pathologies. PMID- 26145010 TI - 3-Hydro-2,2,5,6-tetramethylpyrazine: A novel inducer of zinc transporter-1 in HepG2 human hepatocellular carcinoma cells. AB - Dihydropyrazine compounds, including 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3), are low-molecular-weight glycation products spontaneously generated in vivo and also ingested via food. Our preliminary study using microarray analysis demonstrated that DHP-3 induced zinc transporter-1 (ZnT-1) in HepG2 cells. It is well known that the increase of intracellular zinc is a sensitive stimulating factor for ZnT-1 protein induction; however, there is little information about the induction of ZnT-1 by low-molecular-weight chemical compounds. Here, we attempted to clarify the mechanism of ZnT-1 induction by DHP-3. A significant increase of ZnT-1 mRNA was observed 6h after DHP-3 treatment at concentrations over 0.5mM, and disappeared 24h after exposure. This induction pattern followed that of metal-responsive transcription factor 1 (MTF-1) mRNA, a metalloregulatory protein that serves as a major transcription factor of ZnT-1. Moreover, DHP-3 yielded transcriptional activation of MTF-1 in a luciferase reporter assay. The intracellular zinc content was unaffected by the compound; however, oxidative stress was observed in cells under the same conditions that activated the MTF-1 signaling pathway. These results suggest that DHP-3 is a novel ZnT-1 inducer and acts via activation of the MTF-1 signaling pathway. Additionally, the activation of MTF-1 by this compound likely occurs through oxidative stress. PMID- 26145038 TI - Icariin, a natural flavonol glycoside, extends healthspan in mice. AB - A major goal of aging research now is to find pharmacological manipulations in healthspan extension. Icariin is a flavonol isolated from medicinal herbal tonics. We have previously reported that icariin extended the healthspan of invertebrate models. Here, we showed that long-term treatment with icariin starting at 12months of age extended healthspan and mean lifespan in C57BL/6 mice. In all our assays associated with healthspan, such as behavioral tests and bone density analysis, we found that icariin boosted healthy features in mice. We also presented data indicating that such beneficial effects of icariin were due to at least two mechanisms: reduced oxidative stress indicated by the induction of antioxidant protein superoxide dismutase (SOD) activity and the decrease of oxidative marker malondialdehyde (MDA); maintained the genomic stability indicated by a reduction in DNA double-stranded breaks and down-regulation of DNA damage response genes. Our results indicated that icariin, a safe and widely used natural flavonol, extended healthspan and maintained genomic stability in a mammalian system. PMID- 26145099 TI - Estimating the prevalence of mixed-type gonococcal infections in Queensland, Australia. AB - Background Mixed gonococcal infections within the one anatomical site have been recognised but questions remain over how often they occur. In this study, the aim was to estimate the prevalence of mixed gonococcal infections using novel real time polymerase chain reaction (PCR) methods that were developed and validated, targeting the gonococcal porB gene. METHODS: Neisseria gonorrhoeae strains were categorised into three different porB groups, based on sequence data derived from N. gonorrhoeae multi-antigen sequence typing (NG-MAST) analyses of local isolates. Specific PCR methods for each group were then developed and these PCR methods were used to test clinical samples (n=350) that were positive for gonorrhoea as determined by nucleic acid amplification test (NAAT) diagnostic screening. RESULTS: Initial validation using isolates showed the group PCR methods proved 100% sensitive and 100% specific for their respective porB groups. When applied to the clinical specimens, 298/350 (85%) provided positive results by the group PCR methods. Of these, four specimens showed evidence of mixed infections, supported by subsequent DNA sequencing of the PCR products. CONCLUSIONS: The data provide further evidence of mixed gonococcal infections at the same anatomical site, but show that such infections may be relatively infrequent (1.3%; 95% confidence interval 0.01-2.6%) in a general screening population. PMID- 26145125 TI - New ester based gemini surfactants: the effect of different cationic headgroups on micellization properties and viscosity of aqueous micellar solution. AB - A new series of ester functionalized cationic gemini surfactants having different cationic headgroups (i.e. piperidinium, pyrrolidinium, morpholinium and quaternary ammonium) have been synthesized and characterized using NMR and Mass spectroscopy. These new gemini surfactants were investigated for their micellization and viscosity properties using surface tension, conductivity, fluorescence and rheology thechniques. The physicochemical properties of the aqueous surfactant system were influenced by polarity, size and the nature of cationic headgroups as the surface, thermodynamic and viscosity properties of these gemini surfactants were found to be dependent on the type of cationic headgroup. The current research finding establishes the structure-property relationship of the surfactant molecule specifically taking into account the dominant role displayed by the nature of the cationic headgroup. PMID- 26145051 TI - Microfluidic assessment of functional culture-derived platelets in human thrombi under flow. AB - Despite their clinical significance, human platelets are not amenable to genetic manipulation, thus forcing a reliance on mouse models. Culture-derived platelets (CDPs) from human peripheral blood CD34(+) cells can be genetically altered and may eventually be used for transfusions. By use of microfluidics, the time dependent incorporation of CD41(+)CD42(+) CDPs into clots was measured using only 54,000 CDPs doped into 27 MUL of human whole blood perfused over collagen at a wall shear rate of 100 sec(-1). With the use of fluorescence-labeled human platelets (instead of CDPs) doped between 0.25% and 2% of total platelets, incorporation was highly quantitative and allowed monitoring of the anti alphaIIbbeta3 antagonism that occurred after collagen adhesion. CDPs were only 15% as efficient as human platelets in their incorporation into human thrombi under flow, although both cell types were equally antagonized by alphaIIbbeta3 inhibition. Transient transfection allowed the monitoring of GFP(+) human CDP incorporation into clots. This assay quantifies genetically altered CDP function under flow. PMID- 26145126 TI - [In Process Citation]. PMID- 26145127 TI - [In Process Citation]. PMID- 26145128 TI - [Amputation, a multidisciplinary treatment]. AB - With more than 8000 new amputees each year in France, mostly as a result of a trauma or vascular problem, the challenges are both surgical and technological. The success of the rehabilitation and readjustment of the patient is the fruit of multidisciplinary care. PMID- 26145129 TI - [The nursing role in field amputation]. AB - Field amputation is a surgical procedure which consists in removing one or several limbs of a victim to extricate them from rubble and evacuate them to a hospital. A last resort, it is a rarely-performed procedure, carried out primarily in disaster medicine. A team which worked in Haiti after the 2010 earthquake reports on one such clinical situation. PMID- 26145130 TI - [The announcement of the need to amputate]. AB - The announcement of a diagnosis is a difficult art. All the more so when it affects the patient's integrity, as is the case with a post-traumatic amputation. As part of the multidisciplinary support provided both prior to as well as after the procedure, the psychologist or psychiatrist has a specific role to play in ensuring the patient's future psychological rehabilitation. PMID- 26145131 TI - [Monitoring and post-operative care of amputation patients]. AB - The aim of postoperative care of a patient having undergone a post-traumatic amputation is to prevent complications and ensure the optimal healing of the amputated limb. The team is especially attentive to pain and supports the patient in their acceptance process. PMID- 26145132 TI - [Phantom limb pains]. AB - With the radical experience of an amputation, the adaptation of body image is often incomplete. Some people experience phantom body perceptions, often painful and difficult to treat, after the amputation of a limb. PMID- 26145133 TI - [The re-education process of the amputee]. AB - In rehabilitation centres, patients having just undergone an amputation are cared for at every stage necessary for their return to daily living. The teams involved coordinate their efforts to provide the local and general care relating to the causal or intercurrent pathology. They also have skills in prostheses. PMID- 26145134 TI - [Reconstructing oneself after an amputation]. AB - Anne, in her forties, was the victim of a serious road traffic accident resulting in the amputation of her foot. Demonstrating strength and modesty, she shares with us the main stages of her journey towards her reconstruction. PMID- 26145135 TI - [Aquapheresis, an innovative technique in cardiology]. AB - Used in France for the last two years, aquapheresis is a technique to remove excess water from patients with heart failure resistant to diuretics. The therapy is delivered during the patient's hospitalisation in a cardiology intensive care unit to ensure optimal monitoring and the prevention of potential complications. A team from Grenoble shares its experience. PMID- 26145136 TI - [In Process Citation]. AB - Psychiatric care and nurse's experience in Lebanon. Psychiatry in Lebanon has developed significantly over the last decade, both in terms of care, university training and research. This article presents the specificities of psychiatric care and the experience of the nurses working in this discipline at Beirut's Hotel-Dieu de France hospital. PMID- 26145137 TI - [In Process Citation]. AB - Pain and treatment of burn patient. The pain of patients with burns must be taken into account early on in their treatment to facilitate their experience in hospital. The treatment of acute pain resulting from dressings, movements and rehabilitation is essential. If they are given the right relief for their day-to day activities, patients will regain their autonomy more quickly. PMID- 26145138 TI - [The role of laughter in palliative care]. AB - A team has studied the impact of laughter in palliative care. For the majority of caregivers, laughter is perceived as a complementary tool for supporting patients, but many are reluctant to use it. Patients, for their part, are receptive to it. Used in the correct doses, laughter can enrich care. PMID- 26145139 TI - [Feedback on the training and supervision of student nurses]. AB - In order to harmonise the supervision of student nurses in the different departments of the same unit, a Parisian hospital team has created a working group. An IT tool for supervising the students to be used by the whole unit is also under development. PMID- 26145140 TI - [Quality of medication storage on hospital wards]. AB - In order to meet regulations and limit the risks for patients, the quality of medication storage on hospital wards requires practical actions. They concern mainly the management of the emergency medication cabinets, conditions regarding supply and cold storage under controlled temperatures. Failures in the system may result in nurses carrying out risky procedures. PMID- 26145141 TI - [In Process Citation]. PMID- 26145142 TI - Battling with Parkinson's for Eight Years. PMID- 26145143 TI - [In Process Citation]. PMID- 26145144 TI - [In Process Citation]. PMID- 26145145 TI - [In Process Citation]. PMID- 26145146 TI - Silica-coated bismuth sulfide nanorods as multimodal contrast agents for a non invasive visualization of the gastrointestinal tract. AB - Non-invasive and real-time imaging of the gastrointestinal (GI) tract is particularly desirable for research and clinical studies of patients with symptoms arising from gastrointestinal diseases. Here, we designed and fabricated silica-coated bismuth sulfide nanorods (Bi2S3@SiO2 NRs) for a non-invasive spatial-temporally imaging of the GI tract. The Bi2S3 NRs were synthesized by a facile solvothermal method and then coated with a SiO2 layer to improve their biocompatibility and stability in the harsh environments of the GI tract, such as the stomach and the small intestine. Due to their strong X-ray- and near infrared absorption abilities, we demonstrate that, following oral administration in mice, the Bi2S3@SiO2 NRs can be used as a dual-modal contrast agent for the real-time and non-invasive visualization of NRs distribution and the GI tract via both X ray computed tomography (CT) and photoacoustic tomography (PAT) techniques. Importantly, integration of PAT with CT provides complementary information on anatomical details with high spatial resolution. In addition, we use Caenorhabditis Elegans (C. Elegans) as a simple model organism to investigate the biological response of Bi2S3@SiO2 NRs by oral administration. The results indicate that these NRs can pass through the GI tract of C. Elegans without inducing notable toxicological effects. The above results suggest that Bi2S3@SiO2 NRs pave an alternative way for the fabrication of multi-modal contrast agents which integrate CT and PAT modalities for a direct and non-invasive visualization of the GI tract with low toxicity. PMID- 26145147 TI - Shape allophiles improve entropic assembly. AB - We investigate a class of "shape allophiles" that fit together like puzzle pieces as a method to access and stabilize desired structures by controlling directional entropic forces. Squares are cut into rectangular halves, which are shaped in an allophilic manner with the goal of re-assembling the squares while self assembling the square lattice. We examine the assembly characteristics of this system via the potential of mean force and torque, and the fraction of particles that entropically bind. We generalize our findings and apply them to self assemble triangles into a square lattice via allophilic shaping. Through these studies we show how shape allophiles can be useful for assembling and stabilizing desired phases with appropriate allophilic design. PMID- 26145148 TI - Inverse Temperature Dependence in Static Quenching versus Calorimetric Exploration: Binding Interaction of Chloramphenicol to beta-Lactoglobulin. AB - The binding interaction between the whey protein bovine beta-lactoglobulin (betaLG) with the well-known antibiotic chloramphenicol (Clp) is explored by monitoring the intrinsic fluorescence of betaLG. Steady-state and time-resolved fluorescence spectral data reveal that quenching of betaLG fluorescence proceeds through ground state complex formation, i.e., static quenching mechanism. However, the drug-protein binding constant is found to vary proportionately with temperature. This anomalous result is explained on the basis of the Arrhenius theory which states that the rate constant varies proportionally with temperature. Thermodynamic parameters like DeltaH, DeltaS, DeltaG, and the stoichiometry for the binding interaction have been estimated by isothermal titration calorimetric (ITC) study. Thermodynamic data show that the binding phenomenon is mainly an entropy driven process suggesting the major role of hydrophobic interaction forces in the Clp-betaLG binding. Constant pressure heat capacity change (DeltaCp) has been calculated from enthalpy of binding at different temperatures which reveals that hydrophobic interaction is the major operating force. The inverse temperature dependence in static quenching is however resolved from ITC data which show that the binding constant regularly decreases with increase in temperature. The modification of native protein conformation due to binding of drug has been monitored by circular dichroism (CD) spectroscopy. The probable binding location of Clp inside betaLG is explored from AutoDock based blind docking simulation. PMID- 26145149 TI - Dual luminescence in solid CuI(piperazine): hypothesis of an emissive 1-D delocalized excited state. AB - Solid [CuI(piperazine)0.5]infinity, characterized by a structure with an infinite double chain of CuI, presents an unexpected dual luminescence. The short copper copper distances allow the existence of both cluster-centered and 1-D delocalized electronic transitions, as emerged from theoretical calculations. Beyond the more common cluster-centered emission a higher energy band, which differs in lifetime and in temperature dependence, is observed. PMID- 26145150 TI - Tuning PCP-Ir complexes: the impact of an N-heterocyclic olefin. AB - A new PCP-type ligand based on an N-heterocyclic olefin (NHO) scaffold has been prepared. The flexibility of this ligand, which is able to adopt facial coordination modes in Ir(I) or meridional in Ir(III) complexes, can be attributed to the dual nature (ylide-olefin) of the NHO scaffold. This results in a rare case of olefin "slippage" that is supported by X-ray crystallography and DFT calculations. PMID- 26145151 TI - Global Analysis Reveals the Crucial Roles of DNA Methylation during Rice Seed Development. AB - Seed development is an important process of reproductive development and consists of embryo and endosperm development; both comprise several key processes. To determine and investigate the functions of the dynamic DNA methylome during seed development, we profiled the DNA methylation genome wide in a series of developmental stages of rice (Oryza sativa) embryo and endosperm by methylcytosine immunoprecipitation followed by Illumina sequencing. The results showed that embryo is hypermethylated predominantly around non-transposable element (TE) genes, short DNA-TEs, and short interspersed TEs compared with endosperm, and non-TE genes have the most diverse methylation status across seed development. In addition, lowly expressed genes are significantly enriched in hypermethylated genes, but not vice versa, confirming the crucial role of DNA methylation in suppressing gene transcription. Further analysis revealed the significantly decreased methylation at early developing stages (from 2 to 3 d after pollination), indicating a predominant role of demethylation during early endosperm development and that genes with a consistent negative correlation between DNA methylation change and expression change may be potentially directly regulated by DNA methylation. Interestingly, comparative analysis of the DNA methylation profiles revealed that both rice indica and japonica subspecies showed robust fluctuant profiles of DNA methylation levels in embryo and endosperm across seed development, with the highest methylation level at 6 d after pollination (2 d after pollination of endosperm in japonica as well), indicating that a complex and finely controlled methylation pattern is closely associated with seed development regulation. The systemic characterization of the dynamic DNA methylome in developing rice seeds will help us understand the effects and mechanism of epigenetic regulation in seed development. PMID- 26145155 TI - Atomic-Scale Interfacial Magnetism in Fe/Graphene Heterojunction. AB - Successful spin injection into graphene makes it a competitive contender in the race to become a key material for quantum computation, or the spin-operation based data processing and sensing. Engineering ferromagnetic metal (FM)/graphene heterojunctions is one of the most promising avenues to realise it, however, their interface magnetism remains an open question up to this day. In any proposed FM/graphene spintronic devices, the best opportunity for spin transport could only be achieved where no magnetic dead layer exists at the FM/graphene interface. Here we present a comprehensive study of the epitaxial Fe/graphene interface by means of X-ray magnetic circular dichroism (XMCD) and density functional theory (DFT) calculations. The experiment has been performed using a specially designed FM1/FM2/graphene structure that to a large extent restores the realistic case of the proposed graphene-based transistors. We have quantitatively observed a reduced but still sizable magnetic moments of the epitaxial Fe ML on graphene, which is well resembled by simulations and can be attributed to the strong hybridization between the Fe 3dz2 and the C 2pz orbitals and the sp orbital-like behavior of the Fe 3d electrons due to the presence of graphene. PMID- 26145157 TI - High-quality bulk hybrid perovskite single crystals within minutes by inverse temperature crystallization. AB - Single crystals of methylammonium lead trihalide perovskites (MAPbX3; MA = CH3NH3(+), X = Br(-) or I(-)) have shown remarkably low trap density and charge transport properties; however, growth of such high-quality semiconductors is a time-consuming process. Here we present a rapid crystal growth process to obtain MAPbX3 single crystals, an order of magnitude faster than previous reports. The process is based on our observation of the substantial decrease of MAPbX3 solubility, in certain solvents, at elevated temperatures. The crystals can be both size- and shape-controlled by manipulating the different crystallization parameters. Despite the rapidity of the method, the grown crystals exhibit transport properties and trap densities comparable to the highest quality MAPbX3 reported to date. The phenomenon of inverse or retrograde solubility and its correlated inverse temperature crystallization strategy present a major step forward for advancing the field on perovskite crystallization. PMID- 26145158 TI - Retention Time Prediction Improves Identification in Nontargeted Lipidomics Approaches. AB - Identification of lipids in nontargeted lipidomics based on liquid-chromatography coupled to mass spectrometry (LC-MS) is still a major issue. While both accurate mass and fragment spectra contain valuable information, retention time (tR) information can be used to augment this data. We present a retention time model based on machine learning approaches which enables an improved assignment of lipid structures and automated annotation of lipidomics data. In contrast to common approaches we used a complex mixture of 201 lipids originating from fat tissue instead of a standard mixture to train a support vector regression (SVR) model including molecular structural features. The cross-validated model achieves a correlation coefficient between predicted and experimental test sample retention times of r = 0.989. Combining our retention time model with identification via accurate mass search (AMS) of lipids against the comprehensive LIPID MAPS database, retention time filtering can significantly reduce the rate of false positives in complex data sets like adipose tissue extracts. In our case, filtering with retention time information removed more than half of the potential identifications, while retaining 95% of the correct identifications. Combination of high-precision retention time prediction and accurate mass can thus significantly narrow down the number of hypotheses to be assessed for lipid identification in complex lipid pattern like tissue profiles. PMID- 26145159 TI - Cognitive training of self-initiation of semantic encoding strategies in schizophrenia: A pilot study. AB - Available cognitive remediation interventions have a significant but relatively small to moderate impact on episodic memory in schizophrenia. The present study aimed to evaluate the efficacy and feasibility of a brief novel episodic memory training targeting the self-initiation of semantic encoding strategies. To select patients with such deficits, 28 participants with schizophrenia performed our Semantic Encoding Memory Task (SEMT) that provides a measure of self-initiated semantic encoding strategies. This task identified a deficit in 13 participants who were then offered two 60-minute training sessions one week apart. After the training, patients performed an alternate version of the SEMT. The CVLT-II (a standardised measure of semantic encoding strategies) and the BVMT-R (a control spatial memory task) were used to quantify memory pre- and post-training. After the training, participants were significantly better at self-initiating semantic encoding strategies in the SEMT (p = .004) and in the CVLT-II (p = .002). No significant differences were found in the BVMT-R. The current study demonstrates that a brief and specific training in memory strategies can help patients to improve a deficient memory process in schizophrenia. Future studies will need to test this intervention further using a randomised controlled trial, and to explore its functional impact. PMID- 26145160 TI - Co-self-assembled nanoaggregates of BODIPY amphiphiles for dual colour imaging of live cells. AB - Co-self-assembled vesicular nanoparticles of two structurally comparable amphiphilic boron-dipyrromethene (BODIPY) dyes with dequenchable dual colour fluorescence were prepared for ratiometric imaging of live cells. PMID- 26145161 TI - Magnetization due to localized states on graphene grain boundary. AB - Magnetism in graphene has been found to originate from various defects, e.g., vacancy, edge formation, add-atoms etc. Here, we discuss about an alternate route of achieving magnetism in graphene via grain boundary. During chemical vapor deposition of graphene, several graphene nucleation centers grow independently and face themselves with unusual bonding environment, giving rise to the formation of grain boundaries. We investigate the origin of magnetism in such grain boundaries within first-principles calculations, by letting two nucleation centers interact with each other at their interface. We observe formation of unprecedented point defect, consisting of fused three-membered and larger carbon rings, which induces net magnetization to graphene quantum dots. In case of periodic lattices, the appearance of array of point defects leads to the formation of magnetic grain boundaries. The net magnetization on these defects arises due to the deviation from bipartite characteristics of pristine graphene. We observe magnetic grain boundary induced dispersion less flat bands near Fermi energy, showing higher localization of electrons. These flat bands can be accessed via small doping, leading to enhanced magnetism. Moreover, the grain boundaries can induce asymmetric spin conduction behavior along the cross boundary direction. These properties can be exploited for sensor and spin filtering applications. PMID- 26145162 TI - Synthesis of 3-chloro-6-((4-(di-tert-butyl[(18)F]fluorosilyl)-benzyl)oxy)-1,2,4,5 tetrazine ([(18)F]SiFA-OTz) for rapid tetrazine-based (18)F-radiolabeling. AB - An efficient method to prepare the (18)F-labeled tetrazine-derivative [(18)F] SiFA-OTz for bioorthogonal radiochemistry was developed. [(18)F]-SiFA-OTz can be synthesized with a radiochemical yield of 78 +/- 5% within 25 min and can quantitatively react with a model strained dienophile, trans-cyclooctenol. PMID- 26145163 TI - Fatal and serious road crashes involving young New Zealand drivers: a latent class clustering approach. AB - The over-representation of young drivers in road crashes remains an important concern worldwide. Cluster analysis has been applied to young driver sub-groups, but its application by analysing crash occurrence is just emerging. We present a classification analysis that advances the field through a holistic overview of crash patterns useful for designing youth-targeted road safety programmes. We compiled a database of 8644 New Zealand crashes from 2002 to 2011 involving at least one 15-24-year-old driver and a fatal or serious injury for at least one road user. We considered crash location, infrastructure characteristics, environmental conditions, demographic characteristics, driving behaviour, and pre crash manoeuvres. The analysis yielded 15 and 8 latent classes of, respectively, single-vehicle and multi-vehicle crashes, and average posterior probabilities measured the odds of correct classification that revealed how the identified clusters contain mostly crashes of a particular class and all the crashes of that class. The results raised three major safety concerns for young drivers that should be addressed: (1) reckless driving and traffic law violations; (2) inattention, error, and hazard perception problems; and (3) interaction with road geometry and lighting conditions, especially on high-speed open roads and state highways. PMID- 26145164 TI - Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease. AB - A minority of Alzheimer disease (AD) patients begin presenting symptoms before the age of 65 years. A familial aggregation is often found in this group of early onset AD, and, in a subset of families, the pattern of inheritance is consistent with autosomal dominant inheritance. Fully penetrant variants in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 are the only causative mutations reported for autosomal dominant AD. This study is to explore the PSEN1 gene mutation in a Tunisian familial Alzheimer's disease. The patient in this family showed a novel missense mutation in exon 4 of the PSEN1 gene (complementary DNA 248T>C), altering isoleucine to threonine at 83 position. Because the change occurred in conserved domains of this gene, and cosegregated with affected family member, we suggested that this change may have a mutagenic and probably pathogenic effect. PMID- 26145165 TI - Preparation of superhydrophobic films based on the diblock copolymer P(TFEMA-r Sty)-b-PCEMA. AB - The diblock copolymer poly[2,2,2-trifluoroethyl methacrylate-r-styrene]-block poly[(2-cinnamoyloxyethyl methacrylate)] [P(TFEMA-r-Sty)-b-PCEMA] was synthesized via atom transfer radical polymerization. The copolymer underwent self-assembly in TFEMA/CH2Cl2 to form spherical micelles. Photo-cross-linking of the PCEMA domains of these micelles yielded cross-linked nanoparticles. The cross-linked nanoparticles were subsequently cast from CH2Cl2/methanol solvent mixtures at methanol volume fractions of more than 30% to yield rough surfaces bearing small nanobumps on micron-sized aggregations that were connected together to form cross linked nanoparticles. These surfaces were superhydrophobic with a water contact angle of 161 +/- 1 degrees and a sliding angle of 6 +/- 1 degrees . Spraying these nanoparticles onto substrates exhibiting microscale roughness, such as filter paper, by a traditional coating technique also created superhydrophobic surfaces. A thin layer of nanoscale spherical protrusions was observed on the microscale fibers of filter paper by scanning electron microscopy. The coated filter paper samples exhibited a water contact angle and a sliding angle of 153 +/- 1 degrees and 9 +/- 1 degrees , respectively. PMID- 26145166 TI - The DNA damage response and immune signaling alliance: Is it good or bad? Nature decides when and where. AB - The characteristic feature of healthy living organisms is the preservation of homeostasis. Compelling evidence highlight that the DNA damage response and repair (DDR/R) and immune response (ImmR) signaling networks work together favoring the harmonized function of (multi)cellular organisms. DNA and RNA viruses activate the DDR/R machinery in the host cells both directly and indirectly. Activation of DDR/R in turn favors the immunogenicity of the incipient cell. Hence, stimulation of DDR/R by exogenous or endogenous insults triggers innate and adaptive ImmR. The immunogenic properties of ionizing radiation, a prototypic DDR/R inducer, serve as suitable examples of how DDR/R stimulation alerts host immunity. Thus, critical cellular danger signals stimulate defense at the systemic level and vice versa. Disruption of DDR/R-ImmR cross talk compromises (multi)cellular integrity, leading to cell-cycle-related and immune defects. The emerging DDR/R-ImmR concept opens up a new avenue of therapeutic options, recalling the Hippocrates quote "everything in excess is opposed by nature." PMID- 26145167 TI - Antibody fusions with immunomodulatory proteins for cancer therapy. AB - The potential of immunomodulatory proteins, in particular cytokines, for cancer therapy is well recognized, but hampered by the toxicity associated with their systemic application. In order to address this problem, targeted delivery by antibody fusion proteins has been early proposed and their development intensively pursued over the last decade. Here, factors influencing the selection and modification of cytokines and antibody formats for this approach are being discussed, indicating current developments and translational advances in the field. PMID- 26145168 TI - TiO2 Nanoparticle Exposure Decreases Spermatogenesis via Biochemical Dysfunctions in the Testis of Male Mice. AB - TiO2 nanoparticles (NPs) have been demonstrated to suppress spermatogenesis in animals, while there is little data related to the biochemical dysfunctions during spermatogenesis due to exposure to TiO2 NPs. In this study, male mice have been exposed to TiO2 NPs via intragastric administration for 60 consecutive days. The findings showed that TiO2 NP exposure resulted in lesions of testis and epididymis, deductions in sperm concentration and sperm motility, and an increase of the number of abnormal sperm in mice. Furthermore, TiO2 NP exposure with 2.5, 5, or 10 mg/kgbw decreased activities of lactate dehydrogenase (-11.59% to 39.84%), sorbitol dehydrogenase (-23.56% to -57.33%), succinate dehydrogenase ( 27.04% to -57.85%), glucose-6-phosphate dehydrogenase (-28.3% to -56.42%), Na(+)/K(+)-ATPase (-15.59% to -53.11%), Ca(2+)-ATPase (-12.44% to -55.41%), and Ca(2+)/Mg(2+)-ATPase (-28.25% to -65.72%), and elevated activities of acid phosphatase (+10.48% to +40.0%), alkaline phosphatase (+20.65% to +64.07%), and total nitric oxide synthase (+0.68- to +2.3-fold) in the testes of mice, respectively. In addition, TiO2 NP exposure caused excessive production of reactive oxygen species (+16.15% to +110.62%), and increased malondialdehyde of lipid peroxidation product (+38.96% to +118.07%), carbonyl of protein oxidative product (+20.98% to +108.1%), and 8-hydroxydeoxyguanosine of DNA oxidative product (+0.9- to +1.83-fold) in the testes, respectively. It implied that spermatogenesis suppression caused by TiO2 NP exposure may be associated with alterations of testicular marked enzymes and oxidative stress in the testes. PMID- 26145169 TI - Nifekalant Versus Amiodarone in the Treatment of Cardiac Arrest: an Experimental Study in a Swine Model of Prolonged Ventricular Fibrillation. AB - PURPOSE: The purpose of the experiment was to compare the effects of nifekalant and amiodarone on the return of spontaneous circulation (ROSC), survival, as well as on the hemodynamic parameters in a swine model of prolonged ventricular fibrillation (VF). METHODS: After 8 min of untreated VF, bolus doses of epinephrine (adrenaline) and either nifekalant, or amiodarone, or saline (n = 10 per group), were administered after randomization. Cardiopulmonary resuscitation (CPR) was commenced immediately after drug administration and defibrillation was attempted 2 min later. CPR was resumed for another 2 min after each defibrillation attempt and the same dose of adrenaline was given every 4th minute during CPR. RESULTS: Forty-eight hour survival was significantly higher with nifekalant compared to amiodarone (p < 0.001) and saline (p = 0.02), (9/10 vs. 0/10 vs. 3/10, respectively). Systolic aortic pressure, diastolic aortic pressure and coronary perfusion pressure were significantly higher with nifekalant during CPR and immediate post-resuscitation period (p < 0.05). The animals in the amiodarone group had a slower heart rate at the 1st and 45th min post-ROSC (p < 0.001 and p = 0.006, respectively). The number of electric shocks required for terminating VF, time to ROSC and adrenaline dose were significantly higher with amiodarone compared to nifekalant (p < 0.001). CONCLUSIONS: Nifekalant showed a more favorable hemodynamic profile and improved survival compared to amiodarone and saline in this swine model. PMID- 26145170 TI - Pathways and Drugs in Pulmonary Arterial Hypertension - Focus on the Role of Endothelin Receptor Antagonists. AB - Pulmonary arterial hypertension (PAH) is a group of diseases characterized by a progressive increase of pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies have here confirmed the prominent role of endothelin (ET)-1 in vasoconstriction and remodelling of the pulmonary microcirculation. In patients who are acute-vasoreactive, classical treatments for PAH are calcium channels blockers (CCBs), while drugs targeting the prostacyclin, nitric oxide and endothelin pathways, i.e., prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), respectively, are indicated in non vasoreactive patients or in vasoreactive patients not responding to initial CCB therapy. Randomised, placebo-controlled trials have shown that ERAs improve pulmonary haemodynamics, exercise capacity, functional status and clinical outcome in patients with PAH. Here we provide an overview of the currently recommended diagnostic and therapeutic work-up in PAH, with special emphasis on ERAs. PMID- 26145171 TI - Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry. AB - The tumor suppressor BRCA2 is thought to facilitate the handoff of ssDNA from replication protein A (RPA) to the RAD51 recombinase during DNA break and replication fork repair by homologous recombination. However, we find that RPA RAD51 exchange requires the BRCA2 partner DSS1. Biochemical, structural, and in vivo analyses reveal that DSS1 allows the BRCA2-DSS1 complex to physically and functionally interact with RPA. Mechanistically, DSS1 acts as a DNA mimic to attenuate the affinity of RPA for ssDNA. A mutation in the solvent-exposed acidic domain of DSS1 compromises the efficacy of RPA-RAD51 exchange. Thus, by targeting RPA and mimicking DNA, DSS1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression. Our findings may provide a paradigm for understanding the roles of DSS1 in other biological processes. PMID- 26145172 TI - A Major Role of DNA Polymerase delta in Replication of Both the Leading and Lagging DNA Strands. AB - Genetic studies with S. cerevisiae Poldelta (pol3-L612M) and Polepsilon (pol2 M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polepsilon is the primary leading strand replicase and that Poldelta is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Poldelta plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Poldelta contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Poldelta, and not Polepsilon, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis. PMID- 26145173 TI - Metabolic Rewiring by Oncogenic BRAF V600E Links Ketogenesis Pathway to BRAF-MEK1 Signaling. AB - Many human cancers share similar metabolic alterations, including the Warburg effect. However, it remains unclear whether oncogene-specific metabolic alterations are required for tumor development. Here we demonstrate a "synthetic lethal" interaction between oncogenic BRAF V600E and a ketogenic enzyme 3-hydroxy 3-methylglutaryl-CoA lyase (HMGCL). HMGCL expression is upregulated in BRAF V600E expressing human primary melanoma and hairy cell leukemia cells. Suppression of HMGCL specifically attenuates proliferation and tumor growth potential of human melanoma cells expressing BRAF V600E. Mechanistically, active BRAF upregulates HMGCL through an octamer transcription factor Oct-1, leading to increased intracellular levels of HMGCL product, acetoacetate, which selectively enhances binding of BRAF V600E but not BRAF wild-type to MEK1 in V600E-positive cancer cells to promote activation of MEK-ERK signaling. These findings reveal a mutation-specific mechanism by which oncogenic BRAF V600E "rewires" metabolic and cell signaling networks and signals through the Oct-1-HMGCL-acetoacetate axis to selectively promote BRAF V600E-dependent tumor development. PMID- 26145174 TI - Selective Suppression of the Splicing-Mediated MicroRNA Pathway by the Terminal Uridyltransferase Tailor. AB - Several terminal uridyltransferases (TUTases) are known to modulate small RNA biogenesis and/or function via diverse mechanisms. Here, we demonstrate that Drosophila splicing-derived pre-miRNAs (mirtrons) are efficiently modified by the previously uncharacterized TUTase, Tailor. Tailor is necessary and sufficient for mirtron hairpin uridylation, and this modification inhibits mirtron biogenesis. Genome-wide analyses demonstrate that mirtrons are dominant Tailor substrates, and three features contribute to substrate specificity. First, reprogramming experiments show Tailor preferentially identifies splicing-derived miRNAs. Second, in vitro tests indicate Tailor prefers substrate hairpins over mature miRNAs. Third, Tailor exhibits sequence preference for 3'-terminal AG, a defining mirtron characteristic. Our work supports the notion that Tailor preferentially suppresses biogenesis of mirtrons, an evolutionarily adventitious pre-miRNA substrate class. Moreover, we detect preferential activity of Tailor on 3'-G canonical pre-miRNAs, and specific depletion of such loci from the pool of conserved miRNAs. Thus, Tailor activity may have had collateral impact on shaping populations of canonical miRNAs. PMID- 26145175 TI - MicroRNA-101 Suppresses Tumor Cell Proliferation by Acting as an Endogenous Proteasome Inhibitor via Targeting the Proteasome Assembly Factor POMP. AB - Proteasome inhibition represents a promising strategy of cancer pharmacotherapy, but resistant tumor cells often emerge. Here we show that the microRNA-101 (miR 101) targets the proteasome maturation protein POMP, leading to impaired proteasome assembly and activity, and resulting in accumulation of p53 and cyclin dependent kinase inhibitors, cell cycle arrest, and apoptosis. miR-101-resistant POMP restores proper turnover of proteasome substrates and re-enables tumor cell growth. In ERalpha-positive breast cancers, miR-101 and POMP levels are inversely correlated, and high miR-101 expression or low POMP expression associates with prolonged survival. Mechanistically, miR-101 expression or POMP knockdown attenuated estrogen-driven transcription. Finally, suppressing POMP is sufficient to overcome tumor cell resistance to the proteasome inhibitor bortezomib. Taken together, proteasome activity can not only be manipulated through drugs, but is also subject to endogenous regulation through miR-101, which targets proteasome biogenesis to control overall protein turnover and tumor cell proliferation. PMID- 26145176 TI - Uridylation of RNA Hairpins by Tailor Confines the Emergence of MicroRNAs in Drosophila. AB - Uridylation of RNA species represents an emerging theme in post-transcriptional gene regulation. In the microRNA pathway, such modifications regulate small RNA biogenesis and stability in plants, worms, and mammals. Here, we report Tailor, an uridylyltransferase that is required for the majority of 3' end modifications of microRNAs in Drosophila and predominantly targets precursor hairpins. Uridylation modulates the characteristic two-nucleotide 3' overhang of microRNA hairpins, which regulates processing by Dicer-1 and destabilizes RNA hairpins. Tailor preferentially uridylates mirtron hairpins, thereby impeding the production of non-canonical microRNAs. Mirtron selectivity is explained by primary sequence specificity of Tailor, selecting substrates ending with a 3' guanosine. In contrast to mirtrons, conserved Drosophila precursor microRNAs are significantly depleted in 3' guanosine, thereby escaping regulatory uridylation. Our data support the hypothesis that evolutionary adaptation to Tailor-directed uridylation shapes the nucleotide composition of precursor microRNA 3' ends. Hence, hairpin uridylation may serve as a barrier for the de novo creation of microRNAs in Drosophila. PMID- 26145177 TI - Quantum simulation of 2D topological physics in a 1D array of optical cavities. AB - Orbital angular momentum of light is a fundamental optical degree of freedom characterized by unlimited number of available angular momentum states. Although this unique property has proved invaluable in diverse recent studies ranging from optical communication to quantum information, it has not been considered useful or even relevant for simulating nontrivial physics problems such as topological phenomena. Contrary to this misconception, we demonstrate the incredible value of orbital angular momentum of light for quantum simulation by showing theoretically how it allows to study a variety of important 2D topological physics in a 1D array of optical cavities. This application for orbital angular momentum of light not only reduces required physical resources but also increases feasible scale of simulation, and thus makes it possible to investigate important topics such as edge-state transport and topological phase transition in a small simulator ready for immediate experimental exploration. PMID- 26145178 TI - Factors Associated with Discussion of Disasters by Final Year High School Students: An International Cross-sectional Survey. AB - Introduction The effect on behavioral change of educational programs developed to reduce the community's disaster informational vulnerability is not known. This study describes the relationship of disaster education, age, sex, and country specific characteristics with students discussing disasters with friends and family, a measure of proactive behavioral change in disaster preparedness. METHODS: Three thousand eight hundred twenty-nine final year high school students were enrolled in an international, multi-center prospective, cross-sectional study using a pre-validated written questionnaire. In order to obtain information from different educational systems, from countries with different risk of exposure to disasters, and from countries with varied economic development status, students from Bahrain, Croatia, Cyprus, Egypt, Greece, Italy, Portugal, Romania, and Timor-Leste were surveyed. Logistic regression analyses examined the relationship between the likelihood of discussing disasters with friends and family (dependent variable) and a series of independent variables (age, gender, participation in school lessons about disasters, existence of a national disaster educational program, ability to list pertinent example of disasters, country's economic group, and disaster risk index) captured by the questionnaire or available as published data. RESULTS: There was no statistically significant relationship between age, awareness of one's surroundings, planning for the future, and foreseeing consequences of events with discussions about potential hazards and risks with friends and/or family. The national educational budget did not have a statistically significant influence. Participants who lived in a low disaster risk and high income Organization for Economic Co-operation and Development (OECD) country were more likely to discuss disasters. While either school lessons or a national disaster education program had a unique, significant contribution to the model, neither had a better predictive utility. CONCLUSIONS: The predictors (national disaster program, school lessons, gender, ability to list examples of disasters, country's disaster risk index, and level of economic development), although significant, were not sufficient in predicting disaster discussions amongst teenagers. PMID- 26145179 TI - Methane emissions from two breeds of beef cows offered diets containing barley straw with either grass silage or brewers' grains. AB - Increasing the concentration of dietary lipid is a promising strategy for reducing methane (CH4) emissions from ruminants. This study investigated the effect of replacing grass silage with brewers' grains on CH4 emissions of pregnant, non-lactating beef cows of two breeds. The experiment was a two*two factorial design comprising two breeds (LIMx, crossbred Limousin; and LUI, purebred Luing) and two diets consisting of (g/kg diet dry matter (DM)) barley straw (687) and grass silage (301, GS), or barley straw (763) and brewers' grains (226, BG), which were offered ad libitum. Replacing GS with BG increased the acid hydrolysed ether extract concentration from 21 to 37 g/kg diet DM. Cows (n=48) were group-housed in equal numbers of each breed across two pens and each diet was allocated to one pen. Before measurements of CH4, individual dry matter intake (DMI), weekly BW and weekly body condition score were measured for a minimum of 3 weeks, following a 4-week period to acclimatise to the diets. CH4 emissions were subsequently measured on one occasion from each cow using individual respiration chambers. Due to occasional equipment failures, CH4 measurements were run over 9 weeks giving 10 observations for each breed*treatment combination (total n=40). There were no differences between diets for daily DMI measured in the chambers (9.92 v. 9.86 kg/day for BG and GS, respectively; P>0.05). Cows offered the BG diet produced less daily CH4 than GS fed cows (131 v. 156 g/day: P0.05). However, when expressed as a proportion of metabolic BW (BW0.75), LUI cows had greater DMI than LIMx cows (84.5 v. 75.7 g DMI/kg BW0.75, P<0.05) and produced more CH4 per kg BW0.75 than LIMx cows (1.30 v. 1.05 g CH4/kg BW0.75; P<0.01). Molar proportions of acetate were higher (P<0.001) and propionate and butyrate lower (P<0.01) in rumen fluid samples from BG-fed compared with GS-fed cows. This study demonstrated that replacing GS with BG in barley straw-based diets can effectively reduce CH4 emissions from beef cows, with no suppression of DMI. PMID- 26145180 TI - The yield of stool testing in hospital-onset diarrhea: Has evidence changed practice? AB - INTRODUCTION: Aside from examination for Clostridium difficile, the yield of stool testing in hospital-onset diarrhea is poor. Clinical practice guidelines discourage overzealous stool testing in patients with diarrhea that develops after the third hospital day. However, the adoption of this recommendation into clinical practice is limited. Furthermore, the effect of microbiology laboratory improvements on hospital-onset diarrhea testing is largely unknown. METHODS: A retrospective cohort study was conducted in a university-affiliated community hospital and included all adult inpatients who developed diarrhea after hospitalization. RESULTS: 132 adult patients (53% female) developed diarrhea after hospitalization in 2013. The cohort's mean age was 55.6 years. 46.2% of patients developed diarrhea in the first 3 days of hospitalization. Testing for parasites was negative in all examined 67 samples. Testing for C. difficile was positive in 13 cases (10.8%) out of 120 tested samples. Testing for other pathogens was positive in 1 sample (Campylobacter) out of 129 samples. Stool samples tested in the first 3 days of hospitalization were more likely to be positive (64.3 vs 35.7%, p = 0.1). Change in management was reported in 9 out of 14 patients (64.3%) with positive stool testing compared with 31 out of 118 patients (26.3%) with negative stool testing, p = 0.01. CONCLUSION: Despite improvements in stool samples' testing, the yield continues to be low, especially in hospital-onset diarrhea past the third hospital day. Physicians' embracement of the '3-day rule' continues to be poor. PMID- 26145181 TI - A New Infracture Technique for Reduction Malarplasty with an L-Shaped Osteotomy Line. AB - BACKGROUND: Reduction malarplasty is one of the most common surgical procedures performed in the Asian population for aesthetic purposes. Although multiple methods have been developed for reduction malarplasty, including a variety of infracture techniques, most of the current procedures have limitations. In the current study we created a new infracture method to circumvent these shortcomings. MATERIAL AND METHODS: Between January 2004 and October 2013, we applied this novel infracture technique in 700 patients. The highest area of the zygomatic body was marked pre-operatively and ground intra-operatively through an intraoral incision. An L-shaped incomplete osteotomy of the zygomatic body was performed with a reciprocating saw, and then a complete perpendicular osteotomy (1 cm anterior to the articular tubercle of the zygomatic arch) was made through a pre-auricular incision. Light pressure on the posterior part of the arch produced a greenstick fracture of the anterior osteotomy site, resulting in posterior-inward repositioning of the malar complex. Internal fixation was not required. RESULTS: Satisfactory aesthetic results and good post-operative stability were achieved. Three months post-operatively, the bone around the zygomatic arc osteotomy line was remodeled. The bone posterior to the articular tubercle of the zygomatic arch was partially absorbed, leading to a depression of the root of the arc and a natural transition on both sides of the osteotomy line, making the midface more slender. Instead, the anterior bone presented with new bones, making the malar complex more stable. CONCLUSIONS: This new method has multiple advantages, including simple manipulation, no need for internal fixation, short operative and recovery times, and few complications. X-ray images showing the bony changes demonstrated that the infracture technique is an effective and ideal method for reduction malarplasty. PMID- 26145182 TI - Endovascular Simulation Leads to Efficiency and Competence in Thoracic Endovascular Aortic Repair Procedures. AB - OBJECTIVE: Endovascular interventions such as thoracic endovascular aortic repair (TEVAR) have largely replaced invasive open procedures, and have been demonstrated to be effective in treating patients. Our study used endovascular simulation to assess the effect of TEVAR rehearsal on surgical trainees at different levels in training. DESIGN: Participants were oriented on an endovascular simulator and subsequently a simulated TEVAR was performed during 4 separate sessions over a 1-month period. Metrics included total procedure/fluoroscopy time and volume of contrast used. Likert scale qualitative analysis evaluated participant's skills involving major procedural steps. Analysis of data across cohorts included 1-way analysis of variance, Kruskal Wallis, and paired t-tests. SETTING: All data were collected at University Hospitals-Case Medical Center, Cleveland, OH. PARTICIPANTS: In all, 12 trainees in 3 cohorts (student, surgery resident postgraduate year [PGY] 1-3, surgery resident/fellow PGY 4-7, n = 4 each) were recruited. RESULTS: All trainees reduced total procedure time (mean = 537 +/- 148 vs 269 +/- 66s, first session vs fourth, P < 0.05, CI: 195-341) and fluoroscopy time (mean = 201 +/- 74 vs 110 +/- 37s, P < 0.05, CI: 51-132) with TEVAR case progression. The student cohort decreased procedure time from 551 +/- 84s to 313 +/- 65s (P < 0.05, CI: 189-287) whereas PGYs 1 to 3 decreased procedure time from 591 +/- 149s to 264 +/- 29s (P < 0.05, CI: 113-541). Use of contrast decreased over time, but the difference was not significant. Participants acquired proficiency after a few runs in most steps of the procedure. The average qualitative score for all groups combined improved significantly (P < 0.03). PGY 4 to 7 trainees had higher technical scores but this was not statistically significant. The initial gap in junior vs senior trainee performance narrowed after a few practice sessions in all aspects evaluated. CONCLUSIONS: TEVAR rehearsal on an endovascular simulator can reduce overall procedure and fluoroscopy time, independent of trainee skill level or experience, as well as improve subjective measures of technical success. Further studies are needed to compare simulator performance to outcomes in live cases. PMID- 26145183 TI - 5-HT1A receptors of the rat dorsal raphe lateral wings and dorsomedial subnuclei differentially control anxiety- and panic-related defensive responses. AB - The dorsal raphe nucleus (DR), the main source of 5-HT projections to brain areas involved in anxiety regulation, is composed by 5 subnuclei that differ morphologically, functionally and neurochemically. Based on immunohistochemical evidence, it has been proposed that whereas 5-HT cells of the dorsomedial (dmDR) and caudal subnuclei are implicated in the pathophysiology of generalized anxiety disorder (GAD), neurons of the lateral wings (lwDR) are associated with panic disorder (PD). We here tested this hypothesis from a behavioral perspective by investigating the consequences of the non-selective stimulation of neurons within the dmDR and lwDR, or the pharmacological manipulation of 5-HT1A receptors located in these nuclei, of male Wistar rats exposed to the elevated T-maze. This test allows the measurement of both a GAD- (i.e. inhibitory avoidance) and a PD- (i.e. escape) related response in the same animal. Intra-dmDR injection of either the excitatory amino acid kainic acid or the 5-HT1A receptor antagonist WAY 100635 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, and inhibited escape expression, a panicolytic-like effect. Microinjection of the 5-HT1A receptor agonist 8-OH-DPAT caused the opposite effect. Administration of the same drugs into the lwDR only altered escape performance. Whereas kainic acid and 8-OH-DPAT facilitated its expression, WAY 100635 inhibited it. At higher doses, kainic acid administration evoked vigorous escape reactions as measured in an open-field. These findings implicate 5-HT neurons of the dmDR in the regulation of both GAD- and PD-related defensive behaviors. They also support a primary role of the lwDR in the mediation of PD associated responses. PMID- 26145184 TI - Influence of wastewater treatment plants' operational conditions on activated sludge microbiological and morphological characteristics. AB - The effect of wastewater composition and operating conditions in activated sludge (AS) microbiological and morphological characteristics was studied in three AS wastewater treatment plants (WWTPs): (a) a high organic load slaughterhouse AS WWTP, operating at complete solids retention, monitored from its start-up and for 425 days; (b) a seasonally operational, low nitrogen load fruit canning industry AS WWTP, operating at complete solids retention, monitored from its start-up and until the end of the season (87 days); (c) a municipal AS WWTP, treating wastewater from a semi-combined sewer system, monitored during the transitions from dry to rainy and again to dry periods of operation. The sludge microbiological and morphological characteristics were correlated to nutrients' availability, solids retention time, hydraulic retention time, dissolved oxygen, mixed liquor suspended solids (MLVSS), organic load (F/M) and substrate utilization rate. The AS WWTPs' operation was distinguished in periods based on biomass growth phase, characterized by different biological and morphological characteristics and on operational conditions. An anoxic/aerobic selector minimizes the readily biodegradable compounds in influent, inhibiting filamentous growth. Plant performance controlling is presented in a logic flowchart in which operational parameters are linked to microbial manipulation, resulting in a useful tool for researchers and engineers. PMID- 26145185 TI - MRI of the cervical spine with 3D gradient echo sequence at 3 T: initial experience. AB - AIM: The aim of this study was to compare three-dimensional (3D) high resolution T2*-weighted gradient echo (3D FFE) magnetic resonance (MR) sequence with conventional 2D T2-weighted turbo spin echo (TSE) MR sequence for imaging of the cervical spine, especially to assess the detectability of the internal anatomy of the cervical spinal cord, i.e. to distinguish the grey and white matter. METHODS: Fifteen volunteers were examined at 3.0T MR unit. Signal-to-noise (SNR), contrast to-noise (CNR) and image homogeneity were evaluated. In the visual analysis, the visibility of anatomical structures of the cervical spine and artifacts were assessed. The nonparametric method of paired sample t-test was adopted to evaluate the differences between the sequences. RESULTS: The 3D FFE sequence provided better results for CNR, cerebrospinal fluid (CSF) versus white matter, grey matter, disk and bone. Moreover, it yielded good results for the CNR grey matter versus white matter. The butterfly-shaped "H" is clearly displayed in the 3D FFE sequence. The statistical analysis revealed the statistically significant difference between the 2D TSE and 3D FFE sequences for the contrast of CSF versus spinal cord (both grey matter and white matter). CONCLUSION: The 3D FFE sequence in MR imaging of the cervical spinal cord is superior in delineation of spinal cord anatomical structures compared to 2D TSE sequence. PMID- 26145186 TI - Clinical relevance of the apparent diffusion coefficient value of metastatic bone tumours on diffusion-weighted MRI images: differences according to the types of primary tumour, the affected bones, and clinical factors. AB - AIM: To evaluate whether the apparent diffusion coefficient (ADC) of metastatic bone tumours on diffusion-weighted magnetic resonance imaging (MRI) images differs according to the type of primary cancer, the affected bone, and clinical factors. MATERIALS AND METHODS: For this retrospective study, two radiologists reviewed MRI images, including ADC maps, of 67 patients (M:F=38:29; median age, 48 years) who were diagnosed with bone metastasis by means of histological or clinical confirmation. The primary tumours included 29 lung adenocarcinomas, 15 invasive ductal adenocarcinomas of the breast, 13 hepatocellular carcinomas, six prostatic carcinomas, and four renal cell carcinomas. ADC values of the metastatic tumour were compared according to the type of primary malignancy, the affected bone, and the age and sex of the patient using Kruskal-Wallis and Mann Whitney U-tests with Bonferroni correction. In addition, pre-contrast CT images were available in 38 of 67 patients; a subanalysis of the CT radiodensity and ADC values were performed with Spearman correlation. RESULTS: The mean, standard deviation, and minimum and maximum values of the ADC of metastatic bone tumours did not differ significantly according to type of primary malignancy, the affected bone, or clinical variables (p>0.1). The ADC value was not significantly correlated with CT radiodensity (p=0.24). Intra- and interobserver agreements for the mean ADC values were excellent (intra-observer: p=0.98; interobserver: p=0.98). CONCLUSIONS: Assessment of the ADC value of metastatic bone tumours is not reliable for differentiation of the type of primary cancer. PMID- 26145187 TI - Effect of faecal occult blood positivity on detection rates and positive predictive value of CT colonography when screening for colorectal neoplasia. AB - AIM: To determine the detection rates and positive predictive value (PPV) of computed tomography (CT) colonography (CTC) according to the magnitude of faecal occult blood test (FOBt) positivity. MATERIALS AND METHODS: Anonymised data from individuals undergoing CTC after a positive FOBt in the English Bowel Cancer Screening Programme were analysed. The detection of colorectal cancer (CRC), advanced neoplasia, and >= 6 mm polyps were stratified by the number of positive FOBt windows. The PPV was calculated by reference to subsequent endoscopy results. The influence of the FOBt result on detection rates was estimated with multilevel logistic regression. PPV, CRC stage, and location were compared across groups according to FOBt positivity. RESULTS: Four thousand, six hundred and one individuals were included (mean = 66.7 years, 54.2% men). Detection rates of CRC and advanced neoplasia increased with greater numbers of positive FOBt windows (odds ratio [OR] for CRC = 1.41; 95% confidence interval [CI]: 1.31-1.52; OR for advanced neoplasia = 1.17; 95%CI: 1.12-1.23; both p < 0.0001). The PPV was significantly greater at higher FOBt levels (p = 0.020). The number of positive FOBt windows had no significant effect on stage (p = 0.30) or location (p = 0.20) of confirmed CRC. CONCLUSIONS: The magnitude of FOBt positivity influences the PPV and detection rates when screening for colorectal neoplasia. CTC may be particularly useful for FOBt patients with few positive test windows. PMID- 26145188 TI - Conductance of a single flexible molecular wire composed of alternating donor and acceptor units. AB - Molecular-scale electronics is mainly concerned by understanding charge transport through individual molecules. A key issue here is the charge transport capability through a single--typically linear--molecule, characterized by the current decay with increasing length. To improve the conductance of individual polymers, molecular design often either involves the use of rigid ribbon/ladder-type structures, thereby sacrificing for flexibility of the molecular wire, or a zero band gap, typically associated with chemical instability. Here we show that a conjugated polymer composed of alternating donor and acceptor repeat units, synthesized directly by an on-surface polymerization, exhibits a very high conductance while maintaining both its flexible structure and a finite band gap. Importantly, electronic delocalization along the wire does not seem to be necessary as proven by spatial mapping of the electronic states along individual molecular wires. Our approach should facilitate the realization of flexible 'soft' molecular-scale circuitry, for example, on bendable substrates. PMID- 26145189 TI - High Risk of Wound Complications Following Direct Anterior Total Hip Arthroplasty in Obese Patients. AB - We sought to identify patient and surgical risk factors for wound complication following direct anterior total hip arthroplasty (THA) and to compare these findings with a group of posterior approach patients. We retrospectively reviewed 716 direct anterior THAs performed by a single surgeon and 3040 posterior THAs from our institution performed from 2010 to 2014. Wound complications were noted in 1.7% of DA cases and 1.9% of posterior cases (P=0.76). Obesity was a stronger risk factor for wound complication in DA patients (HR 4.3, P=0.018) than in posterior approach patients (HR 1.4, P=0.22). The increased risk of wound complication should be taken into consideration prior to direct anterior THA in obese patients. PMID- 26145190 TI - Topical Application of Tranexamic Acid Plus Diluted Epinephrine Reduces Postoperative Hidden Blood Loss in Total Hip Arthroplasty. AB - We evaluated the efficacy and safety of topical application of tranexamic acid (TXA) plus diluted epinephrine (DEP) and its effect on perioperative hidden blood loss and transfusion requirement in primary unilateral total hip arthroplasty (THA). We randomized 107 patients undergoing THA into two groups: 53 received intra-articular TXA 3 g plus 1:200,000 DEP 0.25 mg; 54 received topical TXA 3 g alone. Results showed that combined administration significantly reduced total blood loss (P=0.009), hidden blood loss (P=0.001) and transfusion rate (1.9 vs. 9.3%) compared with TXA alone, without increasing the risks of thromboembolic and hemodynamic complications. Topical TXA plus DEP in THA can decrease postoperative hidden blood loss and avoid homologous transfusion without substantial complications. PMID- 26145191 TI - The Incidence and Short Term Functional Effect of Partial PCL Release in Fixed and Mobile Bearing PCL Retaining TKA. AB - Posterior cruciate ligament (PCL) release may be required to balance the flexion gap in PCL retaining TKA. This study examines the incidence and functional consequences of PCL release in both fixed and mobile bearing TKA. A consecutive series of 1388 TKAs with 1014 fixed bearing, and 374 mobile bearing implants were reviewed for prevalence of partial PCL release, restoration of potential flexion and objective knee stability at minimum one-year follow-up. Patients receiving mobile bearing inserts were more likely to need partial PCL release (42% versus 17.5%). The occurrence of partial PCL release did not have a significant impact on knee range of motion and subjective knee stability. The need for a partial PCL release appears to be greater in mobile than in fixed bearing. Knees that required a release in both groups demonstrated no difference in restoration of flexion compared with unreleased knees and no adverse effects on flexion stability. PMID- 26145192 TI - A-type ECG and EGCG dimers disturb the structure of 3T3-L1 cell membrane and strongly inhibit its differentiation by targeting peroxisome proliferator activated receptor gamma with miR-27 involved mechanism. AB - The effects of four proanthocyanidin dimers including epicatechin-(4beta->8, 2beta->O->7)-epicatechin (A-type EC dimer), epicatechin-(4beta->8)-epicatechin (B type EC dimer), epicatechin-3-gallate-(4beta->8, 2beta->O->7)-epicatechin-3 gallate (A-type ECG dimer) and epigallocatechin-3-gallate-(4beta->8, 2beta->O->7) epigallocatechin-3-gallate (A-type EGCG dimer) on 3T3-L1 preadipocyte cell differentiation and the underlying mechanisms were explored and compared. The results showed that A-type ECG dimer and A-type EGCG dimer significantly reduced the intracellular lipid accumulation in 3T3-L1 preadipocyte cells by targeting miR-27a and miR-27b as well as peroxisome proliferator-activated receptor gamma (PPARgamma) in the early stage of differentiation, while A-type EC dimer and B type EC dimer showed little effect. In addition, our results revealed that the inhibitory effects of proanthocyanidin dimers on 3T3-L1 preadipocyte differentiation were highly structure-dependent and the effects were associated with the dimer-membrane interactions. The presence of galloyl moieties and A-type linkage within the structure of proanthocyanidins might be crucial for their inhibitory effect on adipogenesis. The strong disturbing effects of A-type ECG and A type EGCG dimers on the fluidity, hydrophobicity and permeability of membrane of 3T3-L1 preadipocyte cell were at least, in part, responsible for their distinct inhibitory effects on adipocyte hyperplasia. PMID- 26145193 TI - Missed opportunities for prevention of perinatal HIV infection. PMID- 26145194 TI - Risk factors for 30-day mortality in patients with pneumonia who receive appropriate initial antibiotics: an observational cohort study. AB - BACKGROUND: Appropriate initial antibiotics are essential for the treatment of infectious diseases. However, some patients with pneumonia might develop adverse outcomes, despite receiving appropriate initial antibiotics. We aimed to clarify the risk factors for 30-day mortality in patients who received appropriate initial antibiotics and to identify potential candidates who would benefit from adjunctive therapy. METHODS: From March 15, to Dec 22, 2010, we did a prospective, observational study at ten medical institutions in hospitalised patients (aged >=20 years) with pneumonia. We did a multivariable logistic regression analysis to calculate odds ratios (ORs) and 95% CI to assess the risk factors for 30-day mortality. This study was registered with the University Medical Information Network in Japan, number UMIN000003306. FINDINGS: The 30-day mortality was 11% (61 of 579 patients) in the appropriate initial antibiotic treatment group and 17% (29 of 168) in the inappropriate initial antibiotic treatment group. Albumin concentration of less than 30 mg/L (adjusted OR 3.39, 95% CI 1.83-6.28), non-ambulatory status (3.34, 1.84-6.05), pH of less than 7.35 (3.13, 1.52-6.42), respiration rate of at least 30 breaths per min (2.33, 1.28 4.24), and blood urea nitrogen of at least 7.14 mmol/L (2.20, 1.13-4.30) were independent risk factors in patients given appropriate initial antibiotic treatment. The 30-day mortality was 1% (one of 126 patients), 1% (two of 168), 17% (23 of 137), 22% (20 of 89), and 44% (14 of 32) for patients with no, one, two, three, and four or five risk factors, respectively. INTERPRETATION: Patients with two or more risk factors were at a higher risk of death during the 30 days assessed than were individuals with no or one risk factor, despite appropriate initial antibiotic treatment. Therefore, adjunctive therapy might be important for improving outcomes in patients with two or more risk factors. FUNDING: Central Japan Lung Study Group. PMID- 26145195 TI - Global elimination of mother-to-child transmission of hepatitis B: revisiting the current strategy. AB - Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a major route of HBV transmission worldwide despite an existing immunoprophylaxis regimen. The implementation of immunoprophylaxis has been challenging, especially in low income and middle-income countries, where MTCT is common, because of difficulty obtaining and delivering the monovalent HBV vaccine and the HBV immunoglobulin. Global control of the HBV epidemic will need improved prevention of MTCT. We discuss research gaps that hinder development of new options for the elimination of MTCT as well as policy changes that may help the current vaccine-based strategy to live up to its full potential. We propose that decreasing hepatitis B viral concentrations before delivery, along with HBV vaccine use, could provide an alternative strategy that would decrease MTCT of HBV. PMID- 26145196 TI - CAP death: what goes wrong when everything is right? PMID- 26145197 TI - Preferences of residents and junior neurologists to attend conferences--an EAYNT survey. PMID- 26145198 TI - Chromosome 12p13 variants contribute to large artery atherosclerotic stroke risk in a Chinese population. AB - Recently, a genome-wide association study (GWAS) identified two common variants (rs12425791 and rs11833579) on Chromosome 12p13 that confer risk for stroke. The aim of this study was to evaluate whether these two variants are associated with risk of large artery atherosclerotic (LAA) stroke in a Chinese population. Rs12425791 and rs11833579 were genotyped using the improved multiple ligase detection reaction in 423 patients with LAA stroke and 423 healthy controls. We found a statistically significantly increased risk of LAA stroke associated with the rs12425791AA genotype (OR=2.28, 95% CI=1.15-4.51) and rs11833579 AA genotype (OR=1.92, 95% CI=1.16-3.15) compared with their GG genotype. When we evaluated these two polymorphisms together, we found that the combined genotypes with 3-4 variant alleles (rs12425791A and rs11833579A) were associated with an increased risk of LAA stroke (OR=2.06, 95% CI=1.26-3.36) compared to 0-2 variants. Moreover, genotype-phenotype correlation analysis showed that rs12425791AA and rs11833579AA carriers had significantly decreased NINJ2 mRNA expression levels in the Chinese population (P=0.003 for rs12425791 and P=0.005 for rs11833579). These results suggested that the rs12425791 and rs11833579 polymorphisms on Chromosome 12p13 may be associated with the risk of LAA stroke and might be used as candidate biomarkers for LAA stroke susceptibility. PMID- 26145199 TI - Brainstem dysfunction protects against syncope in multiple sclerosis. AB - BACKGROUND: The aim of this study was to investigate the correlation between autonomic dysfunction in multiple sclerosis (MS) and brainstem dysfunction evaluated with the vestibular evoked myogenic potentials (VEMP) score and conventional MRI. METHODS: Forty-five patients with the diagnosis of clinically isolated syndrome (CIS) suggestive of MS were enrolled. VEMP, heart rate, and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing, and pain provoked head-up tilt table test, as well as brain and spinal cord MRI were performed. RESULTS: There was no difference in the VEMP score between patients with and without signs of sympathetic or parasympathetic dysfunction. However, patients with syncope had significantly lower VEMP score compared to patients without syncope (p<0.01). Patients with orthostatic hypotension (OH) showed a trend of higher VEMP score compared to patients without OH (p=0.06). There was no difference in the presence of lesions in the brainstem or cervical spinal cord between patients with or without any of the studied autonomic parameters. The model consisting of a VEMP score of <=5 and normal MRI of the midbrain and cervical spinal cord has sensitivity and specificity of 83% for the possibility that the patient with MS can develop syncope. CONCLUSIONS: Pathophysiological mechanisms underlying functional and structural disorders of autonomic nervous system in MS differ significantly. While preserved brainstem function is needed for development of syncope, structural disorders like OH could be associated with brainstem dysfunction. PMID- 26145200 TI - Severe bilateral optic neuritis post hepatitis A virus (HAV) and typhoid fever vaccination. PMID- 26145201 TI - Neisseria gonorrhoeae and fosfomycin: Past, present and future. AB - Drug-resistant Neisseria gonorrhoeae has become a global health concern that requires immediate attention. Due to increasing resistance to cephalosporins, pursuing novel alternatives for treating N. gonorrhoeae infections is paramount. Whilst new drug development is often cumbersome, reviving antiquated antibiotic agents for treatment of modern infections has become prevalent in clinical practice. Fosfomycin exhibits bactericidal activity through a unique mechanism of action, and a variety of organisms including N. gonorrhoeae are susceptible. In vitro studies have demonstrated that fosfomycin can retain activity against ceftriaxone-resistant N. gonorrhoeae; however, it remains unclear whether there is synergy between fosfomycin and other antibiotics. Clinical investigations evaluating fosfomycin for the treatment of N. gonorrhoeae infections are confounded by methodological limitations, none the less they do provide some perspective on its potential role in therapy. Future studies are needed to establish a safe, convenient and effective fosfomycin regimen for treating N. gonorrhoeae infections. PMID- 26145203 TI - Suboptimal nutrient balancing despite dietary choice in glucose-averse German cockroaches, Blattella germanica. AB - Insects have evolved fine-tuned gustatory and post-ingestive physiological mechanisms that enable them to self-select an optimal composition of macronutrients. Their ability to forage optimally among multiple food sources and maximize fitness parameters depends on their ability not only to taste and perceive the nutritional value of potential foods but also to avoid deleterious components; the strength of such avoidance should reflect the severity of the perceived hazard. In German cockroaches (Blattella germanica), glucose aversion has evolved in some populations in response to anthropogenic selection with glucose-containing insecticidal baits. In four feeding treatments, we gave newly eclosed glucose-averse female cockroaches free choice to feed from two artificial, nutritionally complementary foods varying in protein and carbohydrate composition, with glucose or fructose as the sole carbohydrate source in either food. After 6days of feeding, we measured diet consumption and the length of basal oocytes as an estimate of sexual maturation. The females did not compromise on their aversion to glucose in order to balance their protein and carbohydrate intake, and experienced lower sexual maturation rates as a consequence. Nutrient specific hunger via feedback mechanisms, and adjustments to gustatory sensitivity thus do not override the deterrence of glucose, likely due to strong selection against ingesting even small amounts of toxin associated with glucose in baits. In the absence of baits, glucose aversion would be expected to incur a fitness cost compared to wild-type individuals due to lower overall food availability but also to larger difficulty in attaining a nutritionally balanced diet. PMID- 26145202 TI - Channels, arrhythmias, and ... the search for the impossible? PMID- 26145204 TI - Clinical and epidemiological characteristics of acute respiratory virus infections in Vietnamese children. AB - Information about viral acute respiratory infections (ARIs) is essential for prevention, diagnosis and treatment, but it is limited in tropical developing countries. This study described the clinical and epidemiological characteristics of ARIs in children hospitalized in Vietnam. Nasopharyngeal samples were collected from children with ARIs at Ho Chi Minh City Children's Hospital 2 between April 2010 and May 2011 in order to detect respiratory viruses by polymerase chain reaction. Viruses were found in 64% of 1082 patients, with 12% being co-infections. The leading detected viruses were human rhinovirus (HRV; 30%), respiratory syncytial virus (RSV; 23.8%), and human bocavirus (HBoV; 7.2%). HRV was detected all year round, while RSV epidemics occurred mainly in the rainy season. Influenza A (FluA) was found in both seasons. The other viruses were predominant in the dry season. HRV was identified in children of all age groups. RSV, parainfluenza virus (PIV) 1, PIV3 and HBoV, and FluA were detected predominantly in children aged 24 months, respectively. Significant associations were found between PIV1 with croup (P < 0.005) and RSV with bronchiolitis (P < 0.005). HBoV and HRV were associated with hypoxia (P < 0.05) and RSV with retraction (P < 0.05). HRV, RSV, and HBoV were detected most frequently and they may increase the severity of ARIs in children. PMID- 26145205 TI - Palatopharyngoplasty with bilateral buccal mucosal graft repair to alleviate oropharyngeal stenosis. AB - Oropharyngeal stenosis is rare, but known complication from tonsillectomy procedure. A 15-year-old female presented with refractory dyspnea, mild obstructive sleep apnea, and dysphagia. She underwent tonsillectomy 3 years prior. Severe cicatricial oropharyngeal scar involving soft palate, anterior tonsillar pillars, and base of tongue, resulted in 1-cm(2) airway. Case report describing lysis of severe palatopharyngeal scar bands from tonsillectomy misadventure with immediate buccal mucosal grafts to repair resultant oropharyngeal defects. Patient no longer complains of difficulty breathing or dysphagia. PMID- 26145227 TI - Association of maternal KIR and fetal HLA-C genes with the risk of preeclampsia in the Chinese Han population, Long et al. PMID- 26145226 TI - Influence of high fat diet and resveratrol supplementation on placental fatty acid uptake in the Japanese macaque. AB - INTRODUCTION: Adequate maternal supply and placental delivery of long chain polyunsaturated fatty acids (LCPUFA) is essential for normal fetal development. In humans, maternal obesity alters placental FA uptake, though the impact of diet remains uncertain. The fatty fetal liver observed in offspring of Japanese macaques fed a high fat diet (HFD) was prevented with resveratrol supplementation during pregnancy. We sought to determine the effect of HFD and resveratrol, a supplement with insulin-sensitizing properties, on placental LCPUFA uptake in this model. METHODS: J. macaques were fed control chow (15% fat, n = 5), HFD (35% fat, n = 10) or HFD containing 0.37% resveratrol (n = 5) prior to- and throughout pregnancy. At ~ 130 d gestation (term = 173 d), placentas were collected by caesarean section. Fatty acid uptake studies using (14)C-labeled oleic acid, arachidonic acid (AA) and docosahexanoic acid (DHA) were performed in placental explants. RESULTS: Resveratrol supplementation increased placental uptake of DHA (P < 0.05), while HFD alone had no measurable effect. Resveratrol increased AMP activated protein kinase activity and mRNA expression of the fatty acid transporters FATP-4, CD36 and FABPpm (P < 0.05). Placental DHA content was decreased in HFD dams; resveratrol had no effect on tissue fatty acid profiles. DISCUSSION: Maternal HFD did not significantly affect placental LCPUFA uptake. Furthermore, resveratrol stimulated placental DHA uptake capacity, AMPK activation and transporter expression. Placental handling of DHA is particularly sensitive to the dramatic alterations in the maternal metabolic phenotype and placental AMPK activity associated with resveratrol supplementation. PMID- 26145225 TI - Corneal structure and transparency. AB - The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. PMID- 26145228 TI - Transcription factors E2F1 and E2F3 are expressed in placenta but do not regulate MMP14. AB - INTRODUCTION: Preeclampsia is a serious complication of pregnancy for which there are no efficacious medical treatments. Soluble endoglin is as an anti-angiogenic factor that contributes to the pathogenesis of the disease, however little is known about its molecular regulation in placenta. Recent data has demonstrated E2F transcription factors directly regulate MMPs in metastatic disease. Of particular interest was the capacity of E2F1 and E2F3 to up-regulate MMP14, a protease that cleaves and releases soluble endoglin from placenta. The aim of this study was to characterize E2F1 and E2F3 in preeclamptic placenta and assess whether silencing affects soluble endoglin release. METHODS: E2F1 and E2F3 mRNA, protein expression and localization were assessed in severe early onset preeclamptic and preterm control placentas (delivered <34 weeks gestation). E2F siRNA was administered to primary trophoblast and primary endothelial cells and effect on MMP14 mRNA expression and soluble endoglin secretion assessed. RESULTS: E2F1 and E2F3 were localized to the syncytiotrophoblast. E2F1 was significantly down regulated in severe preeclamptic placentas, while E2F3 was unchanged. Silencing E2F1 did not decrease MMP14 expression in primary trophoblast or endothelial cells. However, E2F1 silencing resulted in a significant increase in soluble endoglin secretion from both cell types, and silencing of E2F3 also significantly increased soluble endoglin release from primary trophoblast. DISCUSSION: This study demonstrates that E2F1 and E2F3 are present within the syncytiotrophoblast of placenta and that E2F1 is reduced in preeclampsia. Although silencing of either E2F1 or E2F3 does not alter MMP14 expression, both appear to regulate soluble endoglin release. PMID- 26145229 TI - Traceless Solid-Phase Synthesis of Trisubstituted Quinazolines. AB - A traceless polymer-supported synthesis of 4-benzoylquinazolines was developed using the following commercially available building blocks: Fmoc-alpha-amino acids, 2-nitrobenzensulfonyl chlorides and alpha-bromoacetophenones. The acyclic intermediates underwent base-catalyzed rearrangement involving C-C and N-N bond formation followed by ring expansion and yielded resin-bound dihydroquinazoline-2 carboxylic acids. After they were released from the resin by treatment with trifluoroacetic acid, base-mediated decarboxylation produced the target quinazolines in moderate-to-high yields and purities. PMID- 26145230 TI - Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to transplantation time. AB - Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research. PMID- 26145248 TI - ACR appropriateness criteria radiologic management of infected fluid collections. AB - The best management of infected fluid collections depends on a careful assessment of clinical and anatomic factors as well as an up-to-date review of the published literature, to be able to select from a host of multidisciplinary treatment options. This article reviews conservative, radiologic, endoscopic, and surgical options and their best application to infected fluid collections as determined by the ACR Appropriateness Criteria Expert Panel on Interventional Radiology. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals, and the application, by the panel, of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID- 26145249 TI - What was old is new again: using the host response to diagnose infectious disease. AB - A century of advances in infectious disease diagnosis and treatment changed the face of medicine. However, challenges continue to develop including multi-drug resistance, globalization that increases pandemic risks and high mortality from severe infections. These challenges can be mitigated through improved diagnostics, focusing on both pathogen discovery and the host response. Here, we review how 'omics' technologies improve sepsis diagnosis, early pathogen identification and personalize therapy. Such host response diagnostics are possible due to the confluence of advanced laboratory techniques (e.g., transcriptomics, metabolomics, proteomics) along with advanced mathematical modeling such as machine learning techniques. The road ahead is promising, but obstacles remain before the impact of such advanced diagnostic modalities is felt at the bedside. PMID- 26145250 TI - Beating the odds: BETs in disease. AB - Bromodomains (BRDs) are evolutionarily conserved protein interaction modules that specifically recognise acetyl-lysine on histones and other proteins, facilitating roles in regulating gene transcription. BRD-containing proteins bound to chromatin loci such as enhancers are often deregulated in disease leading to aberrant expression of proinflammatory cytokines and growth-promoting genes. Recent developments targeting the bromo and extraterminal (BET) subset of BRD proteins demonstrated remarkable efficacy in murine models providing a compelling rationale for drug development and translation to the clinic. Here we summarise recent advances in our understanding of the roles of BETs in regulating gene transcription in normal and diseased tissue as well as the current status of their clinical translation. PMID- 26145251 TI - Derivation of a clinical decision rule for predictive factors for the development of pharyngocutaneous fistula postlaryngectomy. AB - INTRODUCTION: Pharyngocutaneous fistula after larynx and hypopharynx cancer surgery can cause several damages. This study's aim was to derive a clinical decision rule to predict pharyngocutaneous fistula development after pharyngolaryngeal cancer surgery. METHODS: A retrospective cohort study was conducted, including all patients performing total laryngectomy/pharyngolaryngectomy (n=171). Association between pertinent variables and pharyngocutaneous fistula development was assessed and a predictive model proposed. RESULTS: American Society of Anesthesiologists scale, chemoradiotherapy, and tracheotomy before surgery were associated with fistula in the univariate analysis. In the multivariate analysis, only American Society of Anesthesiologists maintained statistical significance. Using logistic regression, a predictive model including the following was derived: American Society of Anesthesiologists, alcohol, chemoradiotherapy, tracheotomy, hemoglobin and albumin pre-surgery, local extension, N-classification, and diabetes mellitus. The model's score area under the curve was 0.76 (95% CI 0.64-0.87). The high-risk group presented specificity of 93%, positive likelihood ratio of 7.10, and positive predictive value of 76%. Including the medium-low, medium-high, and high risk groups, a sensitivity of 92%, negative likelihood ratio of 0.25, and negative predictive value of 89% were observed. CONCLUSION: A clinical decision rule was created to identify patients with high risk of pharyngocutaneous fistula development. Prognostic accuracy measures were substantial. Nevertheless, it is essential to conduct larger prospective studies for validation and refinement. PMID- 26145252 TI - Gamete Dialogs in Green Lineages. AB - Gamete fusion is a core process of sexual reproduction and, in both plants and animals, different sex gametes fuse within species. Although most of the molecular factors involved in gamete interaction are still unknown in various sex possessing eukaryotes, reports of such factors in algae and land plants have been increasing in the past decade. In particular, knowledge of gamete interaction in flowering plants and green algae has increased since the identification of the conserved gamete fusion factor generative cell specific 1/hapless 2 (GCS1/HAP2). GCS1 was first identified as a pollen generative cell-specific transmembrane protein in the lily (Lilium longiflorum), and was then shown to function not only in flowering plant gamete fusion but also in various eukaryotes, including unicellular protists and metazoans. In addition, although initially restricted to Chlamydomonas, knowledge of gamete attachment in flowering plants was also acquired. This review focuses on recent progress in the study of gamete interaction in volvocine green algae and flowering plants and discusses conserved mechanisms of gamete recognition, attachment, and fusion leading to zygote formation. PMID- 26145253 TI - Vitamin D and Vitamin D Receptor in Asthma and Allergy. PMID- 26145254 TI - Impact of the Triglycerides to High-Density Lipoprotein Cholesterol Ratio on the Incidence and Progression of CKD: A Longitudinal Study in a Large Japanese Population. AB - BACKGROUND: The impact of the triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio on chronic kidney disease (CKD) is unclear. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 124,700 participants aged 39 to 74 years in the Japanese Specific Health Check and Guidance System, including 50,392 men, 74,308 women, 102,900 without CKD, and 21,800 with CKD. PREDICTOR: Quartiles of TG:HDL-C ratio. OUTCOMES & MEASUREMENTS: Changes in estimated glomerular filtration rate (eGFR) and urinary protein excretion during the 2-year study period. Incident CKD in participants without CKD, and progression of CKD in participants with CKD. RESULTS: In the entire study population, higher quartile of TG:HDL-C ratio at baseline was significantly associated with greater decline in eGFR and increase in urinary protein excretion during the 2-year study period, even after adjustment for confounding factors. A higher ratio was associated with higher risk of incident CKD in participants without CKD and higher risk of rapid decline in eGFR and increase in urinary protein excretion in participants with CKD. Higher TG:HDL-C ratio was more strongly associated with decline in eGFR (P for interaction = 0.002) and with incident CKD (P for interaction = 0.05) in participants with diabetes than without diabetes. LIMITATIONS: Short observation period and single measurement of all variables. CONCLUSIONS: A higher TG:HDL-C ratio affects the decline in eGFR and incidence and progression of CKD in the Japanese population. PMID- 26145271 TI - "He just has to like ham" - The centrality of meat in home and consumer studies. AB - This study aimed to describe Discourses on meat in the school subject Home and Consumer Studies in five different northern Swedish schools. Fifty-nine students and five teachers from five different schools were recorded and in some cases video-taped during lessons. Results indicate that meat was seen as central to nutritional health, sensory experience, culture and social relationships. This positive view was challenged by an alternative Discourse where meat was threatening to health, sensory experience and psychological comfort, but this was not strong enough to affect centrality. Even when participants sought to promote the health advantages of reducing meat consumption, the dominant centrality Discourse was strengthened. This implies that the possible tension between physical and psychosocial/emotional health can make the benefits of a reduction difficult both to convey and accept. A form of critical food literacy may help teachers deconstruct the arbitrary power of the centrality Discourse, but it may also strengthen meat-eater identities because the social norms that guide food choice become salient. A redesign of Discourses might facilitate a reduction in meat consumption, but such a paradigm shift is dependent on the development of society as a whole, and can only be briefly touched upon within the limited time frames and resources of Home and Consumer Studies. PMID- 26145272 TI - Effect of sensory exposure on liking for fat- or sugar-reduced biscuits. AB - This study investigates the effect of exposure to fat- or sugar-reduced biscuits on liking for these products. Two sets of biscuits were manufactured, each including a standard variant and 4 variants differing by the level of reduction of either fat or sugar content, to 33% of fat content or 28% of sugar content. Biscuit consumers were recruited to eat either the fat (n = 113) or the sugar reduced set of biscuits (n = 106). They participated in 5 testing sessions, once a week, in laboratory conditions. During each session, they rated their liking of the 5 variants. At the end of each of the 4 first sessions, consumers were given 16 biscuits for their home consumption during the week. Participants were split into 3 groups of exposure: every week, a control group received the standard variant, a "direct" group received the most reduced variant and a "stepwise" group received a more and more reduced variant. After both control and stepwise exposure, almost no evolution of liking was observed. At the end of the direct exposure period to the 33% fat-reduced variant, liking for this variant significantly improved. On the contrary, after the direct exposure to the 28% sugar-reduced variant, liking only improved for 9 and 16% sugar-reduced variants. PMID- 26145273 TI - Eating behaviour in treatment-seeking obese subjects - Influence of sex and BMI classes. AB - Obese subjects frequently show an adversely altered eating behaviour. However, little is known on differences in eating behaviour across different degree of obesity. We analysed data on the three factor eating questionnaire assessing cognitive restraint, disinhibition, and hunger that were filled in by 664 obese patients (469 women) who seeked treatment in our Interdisciplinary Obesity Center. Patients were divided in five BMI classes (30 - <35 kg/m(2), 35 - <40 kg/m(2), 40 - <50 kg/m(2), and >50 kg/m(2)). Multivariate regression analyses revealed that sex was significantly related to all three eating behaviour traits (all P < 0.042) but no significant relation to BMI (as a continuous variable) was observed. Women in comparison to men showed significantly higher cognitive restraint (9.7 +/- 4.3 vs. 7.7 +/- 4.4; P < 0.001) and disinhibition (9.0 +/- 3.5 vs. 7.7 +/- 3.5; P < 0.001) scores and also showed higher hunger scores (6.9 +/- 3.7 vs. 6.3 +/- 3.5; P = 0.042). Analyses on different BMI classes revealed that cognitive restraint decreased (P = 0.016) while disinhibition (P = 0.010) and hunger (P = 0.044) increased independently of sex with increasing BMI classes. However, above the obesity grade I class (i.e. BMI 30 - < 35 kg/m(2)) there were no differences in eating behaviour variables between the remaining BMI classes. Data indicate profound differences in eating behaviour between women and men that persist across a wide range of obesity. Furthermore, data suggest that while grade I obese patients show higher cognitive restraint and less disinhibition and hunger scores than more severe obese patients these dimensions of eating behaviour do not systematically vary across higher BMI classes. PMID- 26145274 TI - Experimental analysis of the effect of taxes and subsides on calories purchased in an on-line supermarket. AB - Taxes and subsidies are a public health approach to improving nutrient quality of food purchases. While taxes or subsidies influence purchasing, it is unclear whether they influence total energy or overall diet quality of foods purchased. Using a within subjects design, selected low nutrient dense foods (e.g. sweetened beverages, candy, salty snacks) were taxed, and fruits and vegetables and bottled water were subsidized by 12.5% or 25% in comparison to a usual price condition for 199 female shoppers in an experimental store. Results showed taxes reduced calories purchased of taxed foods (coefficient = -6.61, CI = -11.94 to -1.28) and subsidies increased calories purchased of subsidized foods (coefficient = 13.74, CI = 8.51 to 18.97). However, no overall effect was observed on total calories purchased. Both taxes and subsidies were associated with a reduction in calories purchased for grains (taxes: coefficient = -6.58, CI = -11.91 to -1.24, subsidies: coefficient = -12.86, CI = -18.08 to -7.63) and subsidies were associated with a reduction in calories purchased for miscellaneous foods (coefficient = -7.40, CI = -12.62 to -2.17) (mostly fats, oils and sugars). Subsidies improved the nutrient quality of foods purchased (coefficient = 0.14, CI = 0.07 to 0.21). These results suggest that taxes and subsidies can influence energy purchased for products taxed or subsidized, but not total energy purchased. However, the improvement in nutrient quality with subsidies indicates that pricing can shift nutritional quality of foods purchased. Research is needed to evaluate if differential pricing strategies based on nutrient quality are associated with reduction in calories and improvement in nutrient quality of foods purchased. PMID- 26145276 TI - The way to her heart? Response to romantic cues is dependent on hunger state and dieting history: An fMRI pilot study. AB - Normal weight historical dieters (HDs) are prone to future weight gain, and show higher levels of brain activation in reward-related regions after having eaten than nondieters (NDs) in response to food stimuli (Ely, Childress, Jagannathan, & Lowe, 2014), a similar pattern to that seen in obesity. We hypothesized that HDs are differentially sensitive after eating to rewards in general, and thus extended prior findings by comparing the same groups' brain activation when viewing romantic pictures compared to neutral stimuli while being scanned in a blood oxygenation level-dependent (BOLD) fMRI paradigm in a fasted and fed state. Results show that 1) in fed relative to fasted conditions, both HDs and NDs were more responsive in areas related to reward and 2) in HDs, greater fed versus fasted activation extended to areas linked to perception and goal-directed behavior. HDs relative to NDs were more responsive to romantic cues in the superior frontal gyrus when fasted and the middle temporal gyrus when fed. This pattern of response is similar to HDs' activation when viewing highly palatable food cues, and is consistent with research showing overlapping brain-based responses to sex, drugs and food. PMID- 26145275 TI - Maternal intuitive eating as a moderator of the association between concern about child weight and restrictive child feeding. AB - Mothers who are concerned about their young child's weight are more likely to use restrictive feeding, which has been associated with increased food seeking behaviors, emotional eating, and overeating in young children across multiple prospective and experimental studies. In the present study, we examined whether mothers' intuitive eating behaviors would moderate the association between their concern about their child's weight and their use of restrictive feeding. In a sample of 180 mothers of young children, two maternal intuitive eating behaviors (i.e., eating for physical reasons, trust in hunger and satiety cues) moderated this association after controlling for maternal age, body mass index, years of education, race/ethnicity, awareness of hunger and satiety cues and perceptions of child weight. More specifically, concern about child weight was unrelated to restrictive feeding for mothers with higher levels of eating for physical reasons and trust in hunger and satiety cues. However, concern about child weight was positively related to restrictive feeding among mothers with lower or average levels of eating for physical reasons and trust in hunger and satiety cues. These findings indicate that it may be important address maternal intuitive eating within interventions designed to improve self-regulated eating in children, as mothers who attend these interventions tend to be highly concerned about their child's weight and, if also low in intuitive eating, may be at risk for using restrictive feeding behaviors that interfere with children's self-regulated eating. PMID- 26145277 TI - Maternal representations of their children in relation to feeding beliefs and practices among low-income mothers of young children. AB - Identifying maternal characteristics in relation to child feeding is important for addressing the current childhood obesity epidemic. The present study examines whether maternal representations of their children are associated with feeding beliefs and practices. Maternal representations refer to mothers' affective and cognitive perspectives regarding their children and their subjective experiences of their relationships with their children. This key maternal characteristic has not been examined in association with maternal feeding. Thus the purpose of the current study was to examine whether maternal representations of their children, reflected by Working Model of the Child Interview typologies (Balanced, Disengaged, or Distorted), were associated with maternal feeding beliefs (Authority, Confidence, and Investment) and practices (Pressure to Eat, Restriction, and Monitoring) among low-income mothers of young children, with maternal education examined as a covariate. Results showed that Balanced mothers were most likely to demonstrate high authority, Distorted mothers were least likely to demonstrate confidence, and Disengaged mothers were least likely to demonstrate investment in child feeding. Moreover, Balanced mothers were least likely to pressure their children to eat. Findings are discussed with regard to implications for the study of childhood obesity and for applied preventions. PMID- 26145278 TI - Child feeding perceptions among mothers with eating disorders. AB - Feeding and eating difficulties are documented among the offspring of mothers with eating disorders. Understanding the perspective of mothers with eating disorders is likely essential to develop parent-based early prevention programs for children of these mothers. In the present study, twenty-nine mothers who were diagnosed with an eating disorder prior to becoming mothers and who currently had toddler age children participated in a semi-structured interview examining maternal functioning and child feeding. The maternal perceptions that emerged from the interviews were sorted into central themes and subcategories using interpretive phenomenological analysis. Data indicate that mothers with eating disorders express preoccupation with their child's eating, shape and weight, and many dilemmas about child feeding. They also reported rarity of family meals and their toddlers' preliminary awareness of maternal symptoms. Maternal concerns regarding child nutrition, feeding and weight were reported as more intense in regards to daughters. These maternal perceptions illuminate the maternal psychological processes that underlie the feeding and eating problems of the children of mothers with lifetime eating disorders. Findings should be addressed in the evaluation, treatment, and research of adult and childhood eating disorders. PMID- 26145280 TI - Short-term effects of Poly(I:C) on gut permeability. AB - The intestinal barrier function depends on an adequate response to pathogens by the epithelium. Toll-like receptor 3 (TLR-3) recognizes double-stranded RNA, a virus-associated molecular pattern. Activation of TLR-3 with Poly(I:C), a synthetic agonist, modulates tissue repair and permeability in other epithelia; however, the effects of local luminal TLR-3 agonists on gut barrier function are unknown. The aim of this investigation was to evaluate short-term effects of Poly(I:C) on rat ileal and colonic permeability ex vivo. We also studied the acute effects of intrarectal administration of Poly(I:C) on colonic barrier function. Ileum tissues displayed decreased transepithelial electrical resistance (TEER) 1h after incubation with 200MUg/mL Poly(I:C); however, the mucosa-to serosa transit of macromolecules (4.4 and 40kDa dextrans - TD4.4 and FD40, respectively) remained unchanged. Conversely, colon tissue preparations stimulated with 200MUg/mL Poly(I:C) showed a decreased thinning of the mucosal layer after 2h and a decreased transit of FD40 after 3h, in comparison to controls. There was no change in colonic TEER after 3h of treatment. In addition, colon tissue taken from rats 6h after an intrarectal administration of 100MUg Poly(I:C) also showed decreased permeability to FD40 in the everted gut sac assay at 3h post-extraction. Tissue morphology remained unchanged. Our results suggest that an acute exposure to Poly(I:C) reduces colon permeability to macromolecules but increases ileum permeability to electrolytes/small molecules ex vivo. Although the mechanism associated to these effects needs further investigation, to our knowledge this is the first report of a direct effect of a TLR-3 ligand in intestinal barrier function and may be of significance to understand region specific interactions between gut mucosa and microbiota. PMID- 26145279 TI - 5-HT(2C) serotonin receptor blockade prevents tau protein hyperphosphorylation and corrects the defect in hippocampal synaptic plasticity caused by a combination of environmental stressors in mice. AB - Exposure to multimodal sensory stressors is an everyday occurrence and sometimes becomes very intense, such as during rave parties or other recreational events. A growing body of evidence suggests that strong environmental stressors might cause neuronal dysfunction on their own in addition to their synergistic action with illicit drugs. Mice were exposed to a combination of physical and sensory stressors that are reminiscent of those encountered in a rave party. However, this is not a model of rave because it lacks the rewarding properties of rave. A 14-h exposure to environmental stressors caused an impairment of hippocampal long term potentiation (LTP) and spatial memory, and an enhanced phosphorylation of tau protein in the CA1 and CA3 regions. These effects were transient and critically depended on the activation of 5-HT2C serotonin receptors, which are highly expressed in the CA1 region. Acute systemic injection of the selective 5 HT2C antagonist, RS-102,221 (2 mg/kg, i.p., 2 min prior the onset of stress), prevented tau hyperphosphorylation and also corrected the defects in hippocampal LTP and spatial memory. These findings suggest that passive exposure to a combination of physical and sensory stressors causes a reversible hippocampal dysfunction, which might compromise mechanisms of synaptic plasticity and spatial memory for a few days. Drugs that block 5-HT2C receptors might protect the hippocampus against the detrimental effect of environmental stressors. PMID- 26145291 TI - How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions. AB - Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7alpha-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology. PMID- 26145292 TI - [Boredom, what drives creativity]. PMID- 26145293 TI - [The child in a household of multiple problems. The meeting with the forgotten child]. PMID- 26145294 TI - [Supporting parenting in families with multiple problems]. AB - Supporting parenthood in families with multiple problems is a major early prevention challenge. Indeed, the factors of vulnerability, especially if they mount up, expose the child to an increased risk of a somatic pathology, developmental delays, learning difficulties and maltreatment. In order to limit the impact of these vulnerabilities on the health of mothers and infants, it is essential to act early, to adapt the working framework and to collaborate within a network. PMID- 26145295 TI - [Do families with multiple problems exist?]. AB - Families with multiple problems raise questions regarding society's responsibility in the marginalisation of some of its members. Withdrawn in themselves, these families seem only to be able to be helped through the intermediary of the child, by turns the whistle blower or the mediator between the family sphere and the outside world. Schools, hospitals, judiciary or educational institutions can help to identify the relational suffering of these families. PMID- 26145296 TI - [Infant development in a family with multiple problems]. AB - Supporting families with multiple problems involves the close cooperation of various disciplines. The babies from these families must be considered as individuals potentially at high risk of developmental problems, who need to be surrounded and protected. Observation enables professionals to get to know these babies and rapidly spot any signs of suffering. Child health nurses have an essential preventive and nursing role. PMID- 26145297 TI - [Observing and supporting the mother-baby bond in maternity hospitals]. AB - The establishment of the mother-baby bond can prove difficult. It is essential to support parents as they get to know their child. Based on the observation of interactions between mothers and their babies, a practical tool has been created by a child health nurse to encourage professionals to be more attentive to the difficulties of bonding, as well as the strong points and resources which mothers can develop. The care management of vulnerable families is thereby optimised. PMID- 26145298 TI - [Parenting problems, observation at home and support in a network]. AB - Supporting parenthood in a family with multiple problems requires a strong network. In the case of difficulties in establishing the initial bonds between a couple and their baby, the perinatal psychiatric team, working with the mother and infant welfare protection service and the adult psychiatry service, can also put in place measures to support this family. PMID- 26145299 TI - [The suffering of professionals working at home with families with multiple problems]. AB - The management of families with multiple problems often adversely affects the many people involved in their case. This suffering at work affects particularly professionals carrying out home visits. Acknowledging this suffering, enabling these professionals to express and give meaning to their feelings is essential in order to enable them to draw on their skills and creativity. PMID- 26145300 TI - [The institutional attitude, support for caring]. PMID- 26145301 TI - [Supporting the family after a diagnosis of cystic fibrosis]. AB - The diagnosis of cystic fibrosis can upset the relationship between parents and their baby. The announcement signals the disappearance of the "perfect child" and it can be associated with a feeling of guilt on the part of the parents. The child health nurse has a central role in supporting the family during this difficult period, in order to favour the parent-child bond. PMID- 26145302 TI - [Child abuse and parenting]. AB - Maltreatment suffered during childhood has long-term consequences which risk impacting on parenthood. Supporting victims of violence in childhood as they adapt to parenthood represents a challenge for health professionals working in perinatal services. PMID- 26145314 TI - The in vitro fungicidal activity of human macrophages against Penicillium marneffei is suppressed by dexamethasone. AB - Penicillium marneffei (P. marneffei) is a pathogenic fungus that can persist in macrophages and cause a life-threatening systemic mycosis in immunocompromised hosts. To elucidate the mechanisms underlying this opportunistic fungal infection, we established the co-culture system of P. marneffei conidia and human monocyte-derived macrophages (MDM) for investigating the interactions between them. And, we impaired the immune state of MDM by the addition of dexamethasone (DEX). Compared with immunocompetent MDM without DEX treatment in response to P. marneffei, DEX could damage MDM function in initiating the innate immune response through decreasing TNF-alpha production and the proportion of P. marneffei conidia in mature phagolysosomes, while the red pigment secretion by P. marneffei conidia was promoted by DEX following MDM lysis. Our data provide the evidence that DEX-treated MDM have a low fungicidal activity against P. marneffei that causes penicilliosis in immunocompromised hosts. PMID- 26145315 TI - Do not get lost in translation: The role of egocentric heading in spatial orientation. AB - Much is known about how different spatial reference frames continually interact to support spatial navigation, but less explored is whether it is more crucial to process object-to-object information or egocentric heading information for effective orientation in a cluttered environment. To address this question, we evaluated the possible influence on spatial performance of an interactive aerial view of different scale (small vs. large) comprising an arrow indicating participants' egocentric heading. Results revealed that the presence of a small interactive aerial view including a visualized larger arrow facilitated the retrieval of stored spatial layout. These data are consistent with recent studies revealing the role of retrosplenial cortex in translating between different spatial reference frames, and may contribute to elucidate the continuous synchronization between the inter-object direction information in the environment with respect to egocentric current heading. PMID- 26145316 TI - Evaluation of the possibility and response characteristics of laser-induced tactile sensation. AB - In this study, we examined the possibility and perceptual response characteristics of tactile sense induced by laser stimulation to the finger with different laser energy densities through human response experiments. 15 healthy adult males and 4 healthy adult females with an age of 22.6+/-2.2 years were tested. A frequency-doubled Q-switched laser was used with a wavelength of 532 nm and a 5 ns pulse width. The experimental trial spanned a total of 30 s and included a rest phase (19 s), a stimulation phase (7 s), and a response phase (4 s). During the rest phase, subjects kept their fingers comfortable. During the stimulation phase, one of three types of laser energy density (13.5, 16.6, 19.8 mJ/cm(2)) or a sham stimulation was used to irradiate the distal phalanx on the right index finger. During the response phase, the cognitive response to the laser stimulation was recorded by a PC by pressing the response button. The confusion matrix was configured to evaluate the possibility that the tactile sense was caused by the laser. In addition, changes in the response characteristics were observed according to three types of laser energy densities. From the analysis of the confusion matrix, the accuracy and sensitivity were not high. In contrast, precision and specificity were found to be high. Furthermore, there was a strong positive correlation between the laser irradiation and tactile perception, indicating that tactile sense can be induced using a laser in a mid air manner. In addition, it was found that as the laser energy density increased, the tactile perception possibility also increased. PMID- 26145386 TI - The clinical significance of isolated loss of lordosis on cervical spine computed tomography in blunt trauma patients: a prospective evaluation of 1,007 patients. AB - BACKGROUND: A negative computed tomographic (CT) scan may be used to rule out cervical spine (c-spine) injury after trauma. Loss of lordosis (LOL) is frequently found as the only CT abnormality. We investigated whether LOL should preclude c-spine clearance. METHODS: All adult trauma patients with isolated LOL at our Level I trauma center (February 1, 2011 to May 31, 2012) were prospectively evaluated. The primary outcome was clinically significant injury on magnetic resonance imaging (MRI), flexion-extension views, and/or repeat physical examination. RESULTS: Of 3,333 patients (40 +/- 17 years, 60% men) with a c-spine CT, 1,007 (30%) had isolated LOL. Among 841 patients with a Glasgow Coma Scale score of 15, no abnormalities were found on MRI, flexion-extension views, and/or repeat examinations, and all collars were removed. Among 166 patients with Glasgow Coma Scale less than 15, 3 (.3%) had minor abnormal MRI findings but no clinically significant injury. CONCLUSION: Isolated LOL on c-spine CT is not associated with a clinically significant injury and should not preclude c-spine clearance. PMID- 26145387 TI - Mesh herniorrhaphy with simultaneous colorectal surgery: a case-matched study from the American College of Surgeons National Surgical Quality Improvement Program. AB - BACKGROUND: The aim of this study is to evaluate the impact of concurrent mesh herniorrhaphy on short-term outcomes of colorectal surgery by using a large, nationwide database. METHODS: Patients who underwent simultaneous ventral hernia repair (VHR) and colorectal surgery between 2005 and 2010 were identified from the American College of Surgeons National Surgical Quality Improvement Program. Patients who underwent VHR with mesh repair were case matched with patients who underwent VHR without mesh based on the type of colorectal procedure, diagnosis, and American Society of Anesthesiologists score. RESULTS: Two hundred sixty-two patients who underwent VHR with mesh were case matched with 524 patients who underwent VHR without mesh. Mean operating time was significantly longer in patients who underwent VHR with mesh (195.8 +/- 98.7 vs 164.3 +/- 84.4 minutes, P < .001). Postoperative morbidity (P = .58), mortality (P = .27), superficial surgical site infection (SSI) (P = .14), deep SSI (P = .38), organ space SSI (P = .17), wound disruption (P > .99), reoperation (P = .48), and length of hospital stay (P = .71) were comparable between the groups. CONCLUSION: The American College of Surgeons National Surgical Quality Improvement Program data suggest that VHR with mesh does not increase 30-day mortality, medical or surgical morbidity in colorectal surgery setting. PMID- 26145388 TI - The influence of sex on outcomes in trauma patients: a meta-analysis. AB - BACKGROUND: This study aims to assess the influence of sex on outcomes among trauma patients, including injury severity, medical resource utility, complications, and mortality. METHODS: A systematic review of the literature was conducted by internet search. Data were extracted from selected studies and analyzed using Stata to compare outcomes between male and female injured patients. RESULTS: Eventually, 19 studies met our inclusion criteria with 100,566 men and 39,762 women. Pooled data revealed that male sex was associated with increased risk of mortality, hospital length of stay, and higher incidence of complications. No difference was detected in injury severity between male and female patients. CONCLUSION: Evidence of this meta-analysis strongly supports the sex dimorphism in the prognosis of trauma patients and further work should be done to decipher potential mechanism. PMID- 26145389 TI - Hepatitis B screening and vaccination: how does a Sexual Health service measure up? AB - Hepatitis B virus (HBV) is a vaccine-preventable disease. Sexual health clinics in New South Wales see a high caseload of populations at risk of HBV, and thus screening and vaccination are part of routine care. Uptake of screening and vaccination at Sydney Sexual Health Centre was assessed and it was found that among 1577 new patients with an elevated risk of HBV infection, 864 (55%) were potentially susceptible. Of those susceptible, the majority were screened (76%) and approximately one-third (35%) were found to be eligible for vaccination. The majority (83%) initiated vaccination. Of concern, however, is that incremental gaps between initiation and completion of the vaccine course resulted in an overall HBV vaccine coverage of 26% among those HBV susceptible. PMID- 26145414 TI - Effect of extended strain fields on point defect phonon scattering in thermoelectric materials. AB - The design of thermoelectric materials often involves the integration of point defects (alloying) as a route to reduce the lattice thermal conductivity. Classically, the point defect scattering strength follows from simple considerations such as mass contrast and the presence of induced strain fields (e.g. radius contrast, coordination changes). While the mass contrast can be easily calculated, the associated strain fields induced by defect chemistry are not readily predicted and are poorly understood. In this work, we use classical and first principles calculations to provide insight into the strain field component of phonon scattering from isoelectronic point defects. Our results also integrate experimental measurements on bulk samples of SnSe and associated alloys with S, Te, Ge, Sr and Ba. These efforts highlight that the strength and extent of the resulting strain field depends strongly on defect chemistry. Strain fields can have a profound impact on the local structure. For example, in alloys containing Ba, the strain fields have significant spatial extent (1 nm in diameter) and produce large shifts in the atomic equilibrium positions (up to 0.5 A). Such chemical complexity suggests that computational assessment of point defects for thermal conductivity depression should be hindered. However, in this work, we present and verify several computational descriptors that correlate well with the experimentally measured strain fields. Furthermore, these descriptors are conceptually transparent and computationally inexpensive, allowing computation to provide a pivotal role in the screening of effective alloys. The further development of point defect engineering could complement or replace nanostructuring when optimizing the thermal conductivity, offering the benefits of thermodynamic stability, and providing more clearly defined defect chemistry. PMID- 26145415 TI - [Nurse, a profession that has a hard time moving forward]. PMID- 26145416 TI - [Pain and cancer]. PMID- 26145417 TI - [Analgesic treatment of cancer pain]. AB - Cancer pain can be nociceptive, neuropathic or mixed. It is linked to the tumour, to the metastases and to the treatments for the disease and is managed by multimodal analgesia corresponding to the pain relief drugs of the WHO's pain ladder, antidepressants, antiepileptic drugs and local anaesthetics. PMID- 26145418 TI - [Care-related pain in patients with cancer]. AB - The pathway of a patient suffering from cancer can stretch over years, marked by multiple examinations, treatments and procedures. These can all result in induced pain which can be prevented thanks to the knowledge and skills of the caregivers along with pharmacological and non-pharmacological treatments. PMID- 26145419 TI - [Role of psychologists in the fight against pain]. AB - Psychologists observe the representations and behaviour which may fuel pain perception. They assure the psychological follow-up of the patient, depending on their needs, and by helping the team give meaning to the behaviour observed. PMID- 26145420 TI - [Patients' questions and caregivers' answers regarding pain]. AB - Today, although the relief from pain is well managed, it is still a major source of anxiety for patients. Caregivers must be attentive to these concerns and communicate with patients in order to determine their specific questions and fears and to provide some answers. PMID- 26145421 TI - [The pain resource nurse in a cancer unit]. AB - The pain resource nurse in oncology works on the wards, upon the teams' request, in situations of complex pain in the context of serious and chronic diseases. She supports and cares for patients providing specific pain relief, in collaboration with an algologist, and is involved in the continuous training of caregivers. PMID- 26145422 TI - [Placement of a portacath under hypnosis]. AB - The portacath reflects the cancer and its future treatments. Its insertion causes high levels of anxiety for patient. Thanks to medical hypnosis, he can use its internal resources to help them manage the situation and the symptoms he feels. PMID- 26145423 TI - [Exploring the facets of perinatal care]. AB - Perinatal care has long been the sector towards which Eloise Cognat has wanted to direct her career. From her initial training, she felt drawn to working closely with the patient and the care practices; the nursing profession was an obvious choice for her. Here she tells us of the fulfilling start to her career. PMID- 26145424 TI - [An innovative policy for supporting pregnant women]. AB - Improving working conditions for pregnant women can boost their feeling of wellbeing in their job. As a result of its innovative work in this area, Seclin general hospital, in the north of France, has received special recognition for its policy in supporting pregnant women. PMID- 26145425 TI - [Improving cancer patients' quality of life]. AB - Nurses draw on their creativity to improve patients' quality of life. A private practice nurse created, with the support of a local network of associations, an original sewing workshop. Patients and volunteers come together to create attractive clothes adapted to the constraints of cancer treatments. PMID- 26145426 TI - [The benefit of the nurse consultation in the atopy school]. AB - Therapeutic education is a key part of the treatment of patients suffering from atopic dermatitis. At Nantes university hospital, a dedicated centre, the atopy school, has been created to this effect. Nurses describe their practice through the clinical situation of a young child. PMID- 26145427 TI - [Nursing research and the Hospital Programme for Nursing and Allied Health Research]. AB - Nursing research is perceived as a way of improving quality of care. As is the case in Britain and Switzerland, this ambitious activity is developing in France, favoured by the raising of nursing studies to university level and boosted by funding from the French ministry of health. A nursing team at Pitie-Salpetriere hospital, in Paris, share their enthusiasm for this new approach. PMID- 26145428 TI - [Caring for teenagers with anorexia]. AB - Anorexia mainly affects young girls, although more and more boys and adults are also concerned. The consequences of eating disorders have a significant impact on young people's health. Nurses play a key role in the therapeutic contract set up during the hospital treatment. PMID- 26145429 TI - [Caring for patients with cancer wounds]. PMID- 26145431 TI - [End-results of ionizing radiations in nuclear medicine]. PMID- 26145432 TI - [Management of amputees in post-traumatic context]. PMID- 26145433 TI - [Blood collection from peripheral vein]. PMID- 26145434 TI - Naked eye instant reversible sensing of Cu(2+) and its in situ imaging in live brine shrimp Artemia. AB - A Cu(2+)-specific colorimetric reversible fluorescent receptor was designed and synthesized which showed a naked eye observable colour change from colourless to pink on addition of an aqueous buffer (pH 7.4) solution of 30 ppb Cu(2+). Short response time (<=5 s) and low detection limit (nearly 3 ppb) make suitable as a reliable "dip-in" open eye sensor for Cu(2+). Bio-imaging application in live brine shrimp Artemia enabled to detect Cu(2+) at as low as 10 ppb exposure. PMID- 26145435 TI - Defect-free zinc-blende structured InAs nanowires realized by in situ two V/III ratio growth in molecular beam epitaxy. AB - In this study, we devised a two-V/III-ratio procedure to control the Au-assisted growth of defect-free InAs nanowires in molecular beam epitaxy. The demonstrated two V/III ratio procedure consists of a first high V/III ratio growth step to prepare the nanowire foundation on the substrate surface, followed by a low V/III ratio step to induce the nanowire growth. By manipulating the V/III ratios in different steps, we have achieved the controlled growth of pure defect-free zinc blende structured InAs nanowires on the GaAs {111} substrates. This study provides an approach to control not only the crystal structure of semiconductor nanowires, but also their structural qualities. PMID- 26145436 TI - Correction: Steady shearing flows of deformable, inelastic spheres. PMID- 26145437 TI - Layer-by-Layer Assembly of Inactivated Poliovirus and N-Trimethyl Chitosan on pH Sensitive Microneedles for Dermal Vaccination. AB - The aim of this work was to coat pH-sensitive microneedle arrays with inactivated polio vaccine (IPV) particles and N-trimethyl chitosan chloride (TMC) via electrostatic interactions, and assess the immunogenicity of the vaccine after topical application of the coated microneedles in rats. The surface of 200 MUm long microneedles was first chemically modified with pH-sensitive (pyridine) groups and then coated with negatively charged IPV and a positively charged polymer (TMC). To obtain a sufficient high antigen dose, 10 layers of IPV were alternately coated with TMC. The binding of IPV and TMC onto pH-sensitive microneedles was quantified and visualized by using fluorescently labeled TMC and IPV. The release of IPV and TMC from the microneedles was evaluated in ex vivo human skin by fluorescence and the immunogenicity of (unlabeled) IPV was assessed after topical application of the coated microneedles in rats. pH-sensitive microneedles were homogeneously coated with 10 layers of both IPV and TMC, resulting in 45 D antigen units IPV and 700 ng TMC per microneedle array. Fluorescence microscopy imaging revealed that both IPV and TMC were released into ex vivo human skin upon application of the coated microneedles. Finally, in vivo application of IPV-TMC-coated pH-sensitive microneedles in rats led to the induction of IPV specific antibody responses, illustrating that they are practically applicable. Topical administration of pH-sensitive microneedles coated with polyelectrolyte multinanolayers of antigens and oppositely charged polymers may be a useful approach for microneedle-based vaccination. PMID- 26145438 TI - Alkynyl-functionalized gold NHC complexes and their coinage metal clusters. AB - Phenylpropynyl-functionalized imidazolium salts, as well as their gold complexes, were prepared in excellent yields affording suitable starting materials for metal cluster synthesis. The reactions of these gold complexes with coinage metal phenylacetylides [M(CCPh)](x) (M = Cu, Ag) resulted in the formation of novel heterometallic hexanuclear clusters which exhibit mixed metallophillic interactions and intense white photoluminescence at low temperature. PMID- 26145444 TI - H2O2-activated triplet-triplet annihilation upconversion via modulation of the fluorescence quantum yields of the triplet acceptor and the triplet-triplet energy-transfer efficiency. AB - Oxidation-activatable triplet-triplet annihilation (TTA) upconversion was achieved with 9,10-bis(diphenylphosphino)-anthracene (BDPPA, nonfluorescent) as an activatable triplet acceptor/emitter, which can be oxidized to BDPPA-O (highly fluorescent) by H2O2 under mild conditions, and thus TTA upconversion was switched on by H2O2. PMID- 26145443 TI - RASA: Robust Alternative Splicing Analysis for Human Transcriptome Arrays. AB - Human transcriptome arrays (HTA) have recently been developed for high-throughput alternative splicing analysis by measuring signals not only from exons but also from exon-exon junctions. Effective use of these rich signals requires the development of computational methods for better gene and alternative splicing analyses. In this work, we introduce a computational method, Robust Alternative Splicing Analysis (RASA), for the analysis of the new transcriptome arrays by effective integration of the exon and junction signals. To increase robustness, RASA calculates the expression of each gene by selecting exons classified as not alternatively spliced. It then identifies alternatively spliced exons that are supported by both exon and junction signals to reduce the false positives. Finally, it detects additional alternative splicing candidates that are supported by only exon signals because the signals from the corresponding junctions are not well detected. RASA was demonstrated with Affymetrix HTAs and its performance was evaluated with mRNA-Seq and RT-PCR. The validation rate is 52.4%, which is a 60% increase when compared with previous methods that do not use selected exons for gene expression calculation and junction signals for splicing detection. These results suggest that RASA significantly improves alternative splicing analyses on HTA platforms. PMID- 26145446 TI - Direct identification of rituximab main isoforms and subunit analysis by online selective comprehensive two-dimensional liquid chromatography-mass spectrometry. AB - In this proof-of-concept study, rituximab, which is a reference therapeutic monoclonal antibody (mAb), was characterized through the implementation of online, selective comprehensive two-dimensional liquid chromatography (sLC*LC) coupled with mass spectrometry (MS), using a middle-up approach. In this setup, cation exchange chromatography (CEX) and reverse-phase liquid chromatography (RPLC) were used as the first and second separation dimensions, respectively. As illustrated in this work, the combination of these two chromatographic modes allows a direct assignment of the identities of CEX peaks, using data from the TOF/MS detector, because RPLC is directly compatible with MS detection, whereas CEX is not. In addition, the resolving power of CEX is often considered to be limited; therefore, this 2D approach provides an improvement in peak capacity and resolution when high-performance second-dimension separations are used, instead of simply using the second-dimension separation as a desalting step. This was particularly relevant when separating rituximab fragments of medium size (25 kDa), whereas most of the resolution was provided by CEX in the case of intact rituximab samples. The analysis of a commercial rituximab sample shows that online sLC*LC-TOF-MS can be used to rapidly characterize mAb samples, yielding the identification of numerous variants, based on the analysis of intact, partially digested, and digested/reduced mAb samples. PMID- 26145447 TI - Focus on ceftazidime-avibactam for optimizing outcomes in complicated intra abdominal and urinary tract infections. AB - INTRODUCTION: Complicated intra-abdominal infections and urinary tract infections are frequently associated with Gram-negative bacteria and treatment can be hampered by the involvement of resistant organisms. A common resistance mechanism is beta-lactamase production which confers resistance to beta-lactam antibiotics. AREAS COVERED: This article summarizes beta-lactamases found among Gram-negative bacteria as well as providing an overview of complicated intra-abdominal infections and urinary tract infections and the impact inappropriate antibiotic therapy and antibiotic resistance has in their treatment. The author reviews the activity of ceftazidime-avibactam , including animal model data and microbiological data from Phase II clinical trials. This article also highlights Phase III clinical trials of ceftazidime-avibactam that are ongoing or completed and briefly discusses other beta-lactamase inhibitor combinations currently in development. EXPERT OPINION: The increasing problem and complexity of beta lactamase resistance has been met by resurgence in the development of beta lactamase inhibitor combinations. These show promise in the treatment of resistant infections. One beta-lactamase inhibitor in advanced development with a broad spectrum of activity is avibactam, covering class A, class C and some class D enzymes. Importantly, the activity of avibactam also includes carbapenemases such as the KPC and OXA-48. The combination of avibactam with the cephalosporin ceftazidime is attractive, given the spectrum of antimicrobial activity and the low toxicity of the cephalosporin class. PMID- 26145449 TI - The use of probabilistic lexicality cues for word segmentation in Chinese reading. AB - In an eye-tracking experiment we examined whether Chinese readers were sensitive to information concerning how often a Chinese character appears as a single character word versus the first character in a two-character word, and whether readers use this information to segment words and adjust the amount of parafoveal processing of subsequent characters during reading. Participants read sentences containing a two-character target word with its first character more or less likely to be a single-character word. The boundary paradigm was used. The boundary appeared between the first character and the second character of the target word, and we manipulated whether readers saw an identity or a pseudocharacter preview of the second character of the target. Linear mixed effects models revealed reduced preview benefit from the second character when the first character was more likely to be a single-character word. This suggests that Chinese readers use probabilistic combinatorial information about the likelihood of a Chinese character being single-character word or a two-character word online to modulate the extent of parafoveal processing. PMID- 26145448 TI - Allostery through the computational microscope: cAMP activation of a canonical signalling domain. AB - Ligand-induced protein allostery plays a central role in modulating cellular signalling pathways. Here using the conserved cyclic nucleotide-binding domain of protein kinase A's (PKA) regulatory subunit as a prototype signalling unit, we combine long-timescale, all-atom molecular dynamics simulations with Markov state models to elucidate the conformational ensembles of PKA's cyclic nucleotide binding domain A for the cAMP-free (apo) and cAMP-bound states. We find that both systems exhibit shallow free-energy landscapes that link functional states through multiple transition pathways. This observation suggests conformational selection as the general mechanism of allostery in this canonical signalling domain. Further, we expose the propagation of the allosteric signal through key structural motifs in the cyclic nucleotide-binding domain and explore the role of kinetics in its function. Our approach integrates disparate lines of experimental data into one cohesive framework to understand structure, dynamics and function in complex biological systems. PMID- 26145451 TI - A MOF platform for incorporation of complementary organic motifs for CO2 binding. AB - CO2 capture is essential for reducing the carbon footprint of coal-fired power plants. Here we show, both experimentally and computationally, a new design strategy for capturing CO2 in nanoporous adsorbents. The approach involves 'complementary organic motifs' (COMs), which have a precise alignment of charge densities that is complementary to the CO2 quadrupole. Two promising COMs were post-synthetically incorporated into a robust metal-organic framework (MOF) material using solvent-assisted ligand incorporation (SALI). We demonstrate that these COM-functionalized MOFs exhibit high capacity and selectivity for CO2 relative to other reported motifs. PMID- 26145452 TI - Synthesis and characterization of a modified "picket fence" porphyrin complex - stronger pi bonding interactions between Fe(ii) and axial ligands. AB - A new, modified "picket fence" porphyrin is synthesized and its bis(imidazole) ligated iron(ii) derivative [Fe(MbenTpivPP)(1-MeIm)(2)] is investigated. X-ray structure determinations demonstrate that [Fe(MbenTpivPP)(1-MeIm)(2)] has structural features of a near planar porphyrin plane, a relative perpendicular ligand orientation, and one unusually large absolute ligand orientation (phi). The combination of these features leads to a new type of species that is different from previously reported analogues. Further structural examination reveals a strong correlation between the mutual ligand orientations (theta) and the axial Fe-N(Im) bond distances, which is detailed for the first time. Mossbauer spectroscopic characterization shows that the low spin derivative has a quadrupole splitting of 0.99 mm s(-1) at 100 K. PMID- 26145450 TI - Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression. AB - Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues. PMID- 26145453 TI - Predictive model of solute transport with reversible adsorption in spatially periodic hierarchical porous media. AB - Solute transport in hierarchical porous media with reversible adsorption is predicted by the volume averaging method. A transient macroscopic advection diffusion equation is derived to describe the multiscale solute transport problem. The theoretical expression of the dispersion tensor is obtained which is the function of pore-scale velocity profile. Steady closure equations are derived to calculate the dispersion tensor. With the aid of pore-scale simulation in unit cells of the hierarchical porous media, the dispersion tensor can be calculated. The model is verified by comparing its predictions and obtaining favorable agreement with results of direct numerical simulations and with experimental data for columns comprised of ordered, porous pillars. It is straightforward to use the model to predict the solute transport behavior in fixed beds packed with particles. PMID- 26145454 TI - Results of a community-based survey of construction safety climate for Hispanic workers. AB - BACKGROUND: Hispanic construction workers experience high rates of occupational injury, likely influenced by individual, organizational, and social factors. OBJECTIVES: To characterize the safety climate of Hispanic construction workers using worker, contractor, and supervisor perceptions of the workplace. METHODS: We developed a 40-item interviewer-assisted survey with six safety climate dimensions and administered it in Spanish and English to construction workers, contractors, and supervisors. A safety climate model, comparing responses and assessing contributing factors was created based on survey responses. RESULTS: While contractors and construction supervisors' (n = 128) scores were higher, all respondents shared a negative perception of safety climate. Construction workers had statistically significantly lower safety climate scores compared to supervisors and contractors (30.6 vs 46.5%, P<0.05). Safety climate scores were not associated with English language ability or years lived in the United States. CONCLUSIONS: We found that Hispanic construction workers in this study experienced a poor safety climate. The Hispanic construction safety climate model we propose can serve as a framework to guide organizational safety interventions and evaluate safety climate improvements. PMID- 26145455 TI - Multivessel Percutaneous Coronary Interventions in the United States: Insights From the Nationwide Inpatient Sample. AB - BACKGROUND: Multivessel coronary artery disease carries significant mortality risk. Comprehensive data on inhospital outcomes following multivessel percutaneous coronary intervention (MVPCI) are sparse. METHODS: We queried the Healthcare Cost and Utilization Project's nationwide inpatient sample (NIS) between 2006 and 2011 using different International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The primary outcome was inhospital all-cause mortality, and the secondary outcome was a composite of inhospital mortality and periprocedural complications. RESULTS: The overall mortality was low at 0.73% following MVPCI. Multivariate analysis revealed that (odds ratio, 95% confidence interval, P value) age (1.63, 1.48-1.79; <.001), female sex (1.19, 1.00-1.42; P = .05), acute myocardial infarction (AMI; 2.97, 2.35-3.74; <.001), shock (17.24, 13.61-21.85; <.001), a higher burden of comorbidities (2.09, 1.32-3.29; .002), and emergent/urgent procedure status (1.67, 1.30-2.16; <.001) are important predictors of primary and secondary outcomes. MVPCI was associated with higher mortality, length of stay (LOS), and cost of care as compared to single vessel single stent PCI. CONCLUSION: MVPCI is associated with higher inhospital mortality, LOS, and hospitalization costs compared to single vessel, single stent PCI. Higher volume hospitals had lower overall postprocedural mortality rate along with shorter LOS and lower hospitalization costs following MVPCI. PMID- 26145456 TI - Estimating trends in the prevalence of problematic cocaine use (1999-2008). AB - OBJECTIVE: To examine trends in the prevalence of problematic cocaine use in a large city and describe the problems encountered when estimating these trends using capture-recapture techniques based on secondary data METHODS: We used clinical data on accident and emergency department episodes at four university hospitals in Barcelona (Spain) between 1999 and 2008 (3 capture periods per year). Users were categorized into two subgroups depending on concomitant heroin use (cocaine plus heroin, cocaine without heroin). RESULTS: The mean age of users was 34 years and 25% were women (2008). The mean number of episodes per user differed between drug subgroups and over time. The estimated total number of cocaine users increased from 6,028 (95% confidence interval [95%CI]: 4,086-9,327) in 1999 to 22,640 (95%CI: 14,001-37,500) in 2006, but decreased thereafter. The prevalence of problematic use of cocaine plus heroin was stable throughout the study. Thus, trends in the prevalence of problematic cocaine use differed depending on concomitant heroin use. CONCLUSION: Our results are consistent with those provided by health surveys and treatment registries. They also highlight the pitfalls of applying the capture-recapture approach to secondary data, and the need for a better understanding of how information is collected and changes over time. PMID- 26145458 TI - Brownian motion of a nano-colloidal particle: the role of the solvent. AB - Brownian motion is a feature of colloidal particles immersed in a liquid-like environment. Usually, it can be described by means of the generalised Langevin equation (GLE) within the framework of the Mori theory. In principle, all quantities that appear in the GLE can be calculated from the molecular information of the whole system, i.e., colloids and solvent molecules. In this work, by means of extensive Molecular Dynamics simulations, we study the effects of the microscopic details and the thermodynamic state of the solvent on the movement of a single nano-colloid. In particular, we consider a two-dimensional model system in which the mass and size of the colloid are two and one orders of magnitude, respectively, larger than the ones associated with the solvent molecules. The latter ones interact via a Lennard-Jones-type potential to tune the nature of the solvent, i.e., it can be either repulsive or attractive. We choose the linear momentum of the Brownian particle as the observable of interest in order to fully describe the Brownian motion within the Mori framework. We particularly focus on the colloid diffusion at different solvent densities and two temperature regimes: high and low (near the critical point) temperatures. To reach our goal, we have rewritten the GLE as a second kind Volterra integral in order to compute the memory kernel in real space. With this kernel, we evaluate the momentum-fluctuating force correlation function, which is of particular relevance since it allows us to establish when the stationarity condition has been reached. Our findings show that even at high temperatures, the details of the attractive interaction potential among solvent molecules induce important changes in the colloid dynamics. Additionally, near the critical point, the dynamical scenario becomes more complex; all the correlation functions decay slowly in an extended time window, however, the memory kernel seems to be only a function of the solvent density. Thus, the explicit inclusion of the solvent in the description of Brownian motion allows us to better understand the behaviour of the memory kernel at those thermodynamic states near the critical region without any further approximation. This information is useful to elaborate more realistic descriptions of Brownian motion that take into account the particular details of the host medium. PMID- 26145457 TI - [The use of Facebook in Spanish associations of rare diseases: how and what is it used for?]. AB - OBJECTIVE: To study whether the use of Facebook is widespread in the field of patient associations for rare diseases and, if so, the purpose for which the site is being used. METHOD: A descriptive study was conducted to determine whether associations within the Spanish Federation for Rare Diseases use Facebook and, if so, the type of use and its objectives. The analysis was performed based on a categorization system that has been used in the field of chronic diseases and has been adapted to the specific characteristics of rare diseases. RESULTS: Associations use Facebook to raise awareness of rare diseases in general and particularly to share content related to psychological, medical and social support, the promotion and dissemination of research, and fundraising. CONCLUSIONS: The alignment between the interests of associations through their presence on Facebook and policy areas of the national strategy for rare diseases is a reason for optimism about the feasibility of using Facebook as a tool for encounters and collaborative work. PMID- 26145459 TI - Classification and biology of tumour associated stromal cells. AB - Stroma is a fundamental component of the tumour microenvironment whereby it supports malignant cell growth and spreading. It consists of different entities including cells of the immune system, vascular structures and fibroblasts. Much attention has recently been paid to fibroblasts since there is compelling evidence that they orchestrate the recruitment of and educate other cells to promote cancer growth. This review proposes to discuss in detail the nomenclature, origin, and biological functions of the different stromal cells residing in tumours. PMID- 26145460 TI - Functional and oncological outcomes of open nephron-sparing surgery for complex renal masses. AB - OBJECTIVE: To present our long-term functional and oncological outcomes in open nephron-sparing surgery for complex renal masses. PATIENTS AND METHODS: We enrolled 584 patients who underwent open partial nephrectomy between January 1995 and May 2014 at our institution; 108 (18.4%) patients had hilar or completely intraparenchymal tumors or both. We compared change in renal function, perioperative complications, and survival outcomes between complex and noncomplex renal masses. RESULTS: Mean tumor diameter was 4.3 and 3.5cm in patients with hilar and completely intraparenchymal lesions, respectively. R.E.N.A.L. nephrometry scores were significantly higher in patients with complex tumors as compared with patients with exophytic tumors. There was no significant difference between mean estimated glomerular filtration rate at last follow-up compared with preoperative mean estimated glomerular filtration rate in any of the groups. The incidence of perioperative complications was similar across all patients groups. Estimated 10-year cancer-specific survival probabilities were 100% in patients with hilar and intraparenchymal tumors. The 10-year recurrence-free survival probabilities were 96% and 95% in patients with hilar and intraparenchymal tumors, respectively. The main limitations include retrospective design and the lack of kidney-specific functional scan. CONCLUSION: Open nephron-sparing surgery should be considered for complex renal masses yielding excellent functional and oncological outcomes without higher incidence of complications. PMID- 26145461 TI - Innovative Approach to the Accumulation of Rubrosterone by Fermentation of Asparagus filicinus with Fusarium oxysporum. AB - Rubrosterone, possessing various remarkable bioactivities, is an insect-molting C19-steroid. However, only very small amounts are available for biological tests due to its limited content from plant sources. Fungi of genus Fusarium have been reported to have the ability to convert C27-steroids into C19-steroids. In this study, Asparagus filicinus, containing a high content of 20-hydroxyecdysone, was utilized to accumulate rubrosterone through solid fermentation by Fusarium oxysporum. The results showed that F. oxysporum had the ability to facilitate the complete biotransformation of 20-hydroxyecdysone to rubrosterone by solid-state fermentation. The present method could be an innovative and efficient approach to accumulate rubrosterone with an outstanding conversion ratio. PMID- 26145462 TI - Medical Physics: Forming and testing solutions to clinical problems. AB - According to the European Federation of Organizations for Medical Physics (EFOMP) policy statement No. 13, "The rapid advance in the use of highly sophisticated equipment and procedures in the medical field increasingly depends on information and communication technology. In spite of the fact that the safety and quality of such technology is vigorously tested before it is placed on the market, it often turns out that the safety and quality is not sufficient when used under hospital working conditions. To improve safety and quality for patient and users, additional safeguards and related monitoring, as well as measures to enhance quality, are required. Furthermore a large number of accidents and incidents happen every year in hospitals and as a consequence a number of patients die or are injured. Medical Physicists are well positioned to contribute towards preventing these kinds of events". The newest developments related to this increasingly important medical speciality were presented during the 8th European Conference of Medical Physics 2014 which was held in Athens, 11-13 September 2014 and hosted by the Hellenic Association of Medical Physicists (HAMP) in collaboration with the EFOMP and are summarized in this issue. PMID- 26145463 TI - Psychopharmacological options for adult patients with anorexia nervosa. AB - The aim of this review was to summarize evidence from research on psychopharmacological options for adult patients with anorexia nervosa (AN). Database searches of MEDLINE and PsycINFO (from January 1966 to January 2014) were performed, and original articles published as full papers, brief reports, case reports, or case series were included. Forty-one papers were screened in detail, and salient characteristics of pharmacological options for AN were summarized for drug classes. The body of evidence for the efficacy of pharmacotherapy in AN was unsatisfactory, the quality of observations was questionable (eg, the majority were not blinded), and sample size was often small. More trials are needed, while considering that nonresponse and nonremission are typical of patients with AN. PMID- 26145464 TI - Corrigendum: Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. PMID- 26145465 TI - Using Professional Organizations to Prepare the Behavioral Health Workforce to Respond to the Needs of Pediatric Populations Impacted by Health-Related Disasters: Guiding Principles and Challenges. AB - Behavioral health professional organizations are in the unique role of aggregating and disseminating information to their membership before, during, and after health-related disasters to promote the integration of behavioral health services into the public health disaster response plan. This article provides a set of 5 principles to direct this undertaking that are based on the current literature and previous evaluation of the online guidance provided by 6 prominent behavioral health professional organizations. These principles use a strengths based approach to prioritize resilience; underscore the importance of context, collaboration, and coordination; recognize the unique needs of pediatric populations; and guide ongoing training and content development in the area of biopsychosocial responses to health-related disasters. Recognizing important innovations and strides made by the behavioral health organizations noted in a previous study, this article recommends additional areas in which behavioral health professional organizations can contribute to overall pandemic disaster preparedness and response efforts. PMID- 26145467 TI - [Osteostimulating effect of bone xenograft on bone tissue regeneration]. AB - The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures. PMID- 26145468 TI - [Complex treatment of generalized gingivitis with mineral therapy]. AB - A comprehensive examination and treatment of 49 students aged 20-25 years diagnosed chronic generalized catarrhal gingivitis (CGCG) were held. Depending on the methods of treatment were created into two groups of observation. The main group comprised 24 patients who along with dental sanitation and treatment of gingivitis took the course of salt treatment for 17 days, as opposed to control group. Hygienic researches and mineralthcrapy were held in a special room (23.6 m2). equipped with sylvite blocks with a total reaction surface 5 m2, salt filters with air ducts filled with wooden plates with mineral fragments. The study of the effectiveness of a comprehensive treatment of young patients with CGCG allowsto gel an information of the positive impact of salt therapyon the clinical condition of marginal periodontal tissues and indeces of oral cavity local immunity. The main curative factorsforming the internal environment of silvinite structures are multicomponent highly dispersed salt aerosol with a defined particle size and aeroionization. Natural salts complex consisting of chlorides of potassium, sodium and magnesium has an anti-inflammatory and immuno modulating effects. PMID- 26145469 TI - [Evaluation of the clinical efficacy of a new composition of tizol with triamcinolon in complex treatment of patients with erosive ulcerous form of lichen planus of the oral mucosa]. AB - The most significant of the primary stages of complex therapy of oral lichen planus (OLP), among causal and pathogenetic therapy is a local conservative treatment. The aim of the study was to evaluate the clinical efficacy of the local use of the new compositions TIZOL with triamcinolon in complex therapy of erosive-ulcerous forms OLP oral mucosa. The study was performed with 47 patients with lichen planus in age from 24 to 70 years with erosive-ulcerous form OLP whose diagnosis was confirmed histologically. The first group included 25 patients in the complex treatment of locally applied composition TIZOL with triamcinolon. The second group of 22 people, who in the complex treatment applied locally 0.5% prednisone ointment. The high efficiency of topical TIZOL with a highly topical steroid in the complex therapy of erosive-ulcerous forms OLP, which was confirmed by the positive clinical dynamics in all patients (100%) and high self-esteem of patients (84% positive ratings), reduced life complete epithelialization of erosions. PMID- 26145470 TI - [The epidemiological relationship of periodontitis, intestinal dysbiosis, atherogenic dyslipidemia and metabolic syndrome]. AB - The study of risk factors for cardio-vascular continuum (CVC), the influence of the digestive tract endobiosis on lipid-carbohydrate metabolism and clinical status, a retrospective analysis of 1000 medical records of patients, suffering from various diseases of internal organs (Gastrointestinal tract, coronary heart disease, type 2 diabetes, obesity) in combination with periodontitis of varying severity, aged 20 to 55 years. A statistically significant relationship is directly proportional to the severity of inflammation of periodontal tissues with body mass index (BMI), especially pronounced in patients with a BMI >=225 kg/m2 which is the "calling card" of the metabolic syndrome - clinical model polymorbidity. PMID- 26145471 TI - [Elaboration of health care quality criteria in maxillofacial surgery]. AB - Criteria of quality of care in oral and maxillofacial surgery should reflect not only the quality of the repair functions of chewing, swallowing, breathing, speech, and should take into account the psycho-emotional condition of the patient; satisfaction of its appearance, quality cosmetic fill configuration of the face, tooth defects, smiles; adaptation to implants and dentures; their quality, the conditions and possibilities of their use. The application of the provisions of the international classification of functioning, disability and health in oral and maxillofacial surgery, is a condition that will allow to unify the approaches to the development of quality criteria of this type of medical care. PMID- 26145472 TI - [Anatomical rationale for elevating revascularized ulnar forearm fasciocutaneous flap for head and neck reconstruction]. AB - In this paper we studied in detail features of the blood supply to the tissues of the forearm of the pools ulnar and radial arteries, the technique of line access and the formation of skin-fascial ulnar flap by using a layered dissection with contrast vessels on non fixed human cadavers. Blood supply of the forearm carried out by branches radial and ulnar arteries, which allows to create in this area radial flap and ulnar flap loo. The size of the skin-fascial ulnar flap can reach 3-10 cm in length, 2-6 cm in width, the length of vessel pedicle of the transplant can reach 12 cm. The research studied the characteristics of blood supply of the forearm and the comparative evaluation of tissue perfusion of the radial and ulnar arteries; proved localization forming ulnar flap. Studies have shown that revascularised skin-fascial ulnar flap may be can be an alternative donor material for elimination of soft tissue defects with less traumatization donor area and reduce upper limb function compared with radial flap. PMID- 26145473 TI - [Indications, feasibility and clinical experience with Vazirani-Akinozi mandibular block in limiting mouth opening and difficult anatomical conditions]. AB - Vazirani-Akinozi technique was used in 82 patient undergoing oral surgery procedures. According to study results Vazirani-Akinozi technique was feasible in 89% of cases and particularly effective in surgical treatment of third lower molars eruption diseases complicated by inflammatory contracture. The method increases mouth opening 1.6-2.3 cm due to the soft-tissue anesthesia and partial anesthesia of masseter nerve. In case of inflammatory contracture of the jaws when inflammatory infiltration is spreading on the masseter muscle the authors recommend to use a combination of Vazirani-Akinozi and Berchet-Dubov techniques. PMID- 26145474 TI - [The atraumatic restorative treatment approach in pediatric dental care: a comparative clinical study]. AB - The aim of this study was to assess and compare the discomfort levels during Atraumatic Restorative Treatment and Minimal Cavity Preparation using rotary instruments and Air abrasion method. The results of the study suggest that ART induces less discomfort, therefore this method can be recommended for children who have a fear of dental procedures as well as for children with intellectual disabilities. PMID- 26145475 TI - [Dental treatment in children with dystrophic form of epidermolysis bullosa]. AB - The aim of the study was to summarize the experience for providing oral health care in children with epidermolysis bullosa (EB) treated in Central Research Institute of Dentistry and Maxillofacial Surgery in 2013-2014. Seven EB patients (5 female and 2 male aged 5-17) with dystrophic form of EB were included in the study. Oral status was recorded (oral hygiene, presence of enamel hypoplasia and intraoral soft tissue lesions). Dental treatment provided included teeth extractions under conscious sedation (6 cases), teeth treatment (both conventional and ART methods) (5 cases) and preventive program (5 cases). All 7 dystrophic EB patients presented with generalized enamel hypoplasia in both primary and permanent dentition. In these patients one should consider using non adhesive face dressings and careful suction pipe positioning as well as applying liniments on cotton rolls not to cause both intraoral and extraoral soft tissue lesions. Sixteen milk teeth were extracted under conscious sedation, in 3 cases the procedure caused significant vestibular scarring. Twelve teeth were treated mostly by ART method (n=1 0) as limited mouth opening made conventional treatment impossible. Dental treatment in dystrophic EB is a real challenge for pediatric dentist. This group of patients requires a special dental rehabilitation plan as they present with generalized enamel hypoplasia and have significant risk of intraoral lesions. PMID- 26145476 TI - [Structure and dynamics of congenital maxillofacial malformation in Yakutiya region]. AB - The aim of the study was to assess structure and dynamics of congenital facial clefts prevalence in Republic Sokha (Yakutiya) in the last 13 years. Both retrospective and prospective study included 423 children with congenital facial malformations. Dynamic analysis showed cyclical changes in the incidence of cleft lip and palate (CLP) and relatively high regional prevalence of CLIP with tendency to increase. The age of parents of children with congenital facial malformations tend to decrease with time. The received epidemiological data prove the need to improve treatment and rehabilitation protocols for CLP patients in Republic Sokha (Yakutiya). PMID- 26145477 TI - Anatomical and spatial matching in imitation: Evidence from left and right brain damaged patients. AB - Imitation is a sensorimotor process whereby the visual information present in the model's movement has to be coupled with the activation of the motor system in the observer. This also implies that greater the similarity between the seen and the produced movement, the easier it will be to execute the movement, a process also known as ideomotor compatibility. Two components can influence the degree of similarity between two movements: the anatomical and the spatial component. The anatomical component is present when the model and imitator move the same body part (e.g., the right hand) while the spatial component is present when the movement of the model and that of the imitator occur at the same spatial position. Imitation can be achieved by relying on both components, but typically the model's and imitator's movements are matched either anatomically or spatially. The aim of this study was to ascertain the contribution of the left and right hemisphere to the imitation accomplished either with anatomical or spatial matching (or with both). Patients with unilateral left and right brain damage performed an ideomotor task and a gesture imitation task. Lesions in the left and right hemispheres gave rise to different performance deficits. Patients with lesions in the left hemisphere showed impaired imitation when anatomical matching was required, and patients with lesions in the right hemisphere showed impaired imitation when spatial matching was required. Lesion analysis further revealed a differential involvement of left and right hemispheric regions, such as the parietal opercula, in supporting imitation in the ideomotor task. Similarly, gesture imitation seemed to rely on different regions in the left and right hemisphere, such as parietal regions in the left hemisphere and premotor, somatosensory and subcortical regions in the right hemisphere. PMID- 26145479 TI - Global stability analysis of humoral immunity virus dynamics model including latently infected cells. AB - In this paper, we propose and analyse a virus dynamics model with humoral immune response including latently infected cells. The incidence rate is given by Beddington-DeAngelis functional response. We have derived two threshold parameters, the basic infection reproduction number R0 and the humoral immune response activation number R1 which completely determined the basic and global properties of the virus dynamics model. By constructing suitable Lyapunov functions and applying LaSalle's invariance principle we have proven that if R0 <= 1, then the infection-free equilibrium is globally asymptotically stable (GAS), if R1 <= 1 < R0, then the chronic-infection equilibrium without humoral immune response is GAS, and if R1 > 1, then the chronic-infection equilibrium with humoral immune response is globally asymptotically stable. These results are further illustrated by numerical simulations. PMID- 26145478 TI - Engineering Human Stem Cell Lines with Inducible Gene Knockout using CRISPR/Cas9. AB - Precise temporal control of gene expression or deletion is critical for elucidating gene function in biological systems. However, the establishment of human pluripotent stem cell (hPSC) lines with inducible gene knockout (iKO) remains challenging. We explored building iKO hPSC lines by combining CRISPR/Cas9 mediated genome editing with the Flp/FRT and Cre/LoxP system. We found that "dual sgRNA targeting" is essential for biallelic knockin of FRT sequences to flank the exon. We further developed a strategy to simultaneously insert an activity controllable recombinase-expressing cassette and remove the drug-resistance gene, thus speeding up the generation of iKO hPSC lines. This two-step strategy was used to establish human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC) lines with iKO of SOX2, PAX6, OTX2, and AGO2, genes that exhibit diverse structural layout and temporal expression patterns. The availability of iKO hPSC lines will substantially transform the way we examine gene function in human cells. PMID- 26145481 TI - Preoperative Presentation of a Variant of Cerebellar Mutism Syndrome in a Young Boy With Juvenile Pilocytic Astrocytoma. PMID- 26145480 TI - The role of mechanics in biological and bio-inspired systems. AB - Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering. PMID- 26145483 TI - Impact of Organizational Stability on Adoption of Quality-Improvement Interventions for Diabetes in Primary Care Settings. AB - OBJECTIVE: Although there have been tremendous advances in diabetes care, including the development of efficacious interventions, there remain considerable challenges in translating these advances into practice. Four primary care networks (PCNs) in Alberta implemented 2 quality-improvement interventions focused on lifestyle and depression as part of the Alberta's Caring for Diabetes (ABCD) project. METHODS: We used the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework to evaluate adoption of the quality-improvement interventions in the PCN setting. We undertook semistructured interviews with PCN staff (n=24); systematic documentation (e.g. field notes) and formal reflections by the research team (n=4). Content analysis was used to interrogate the data. RESULTS: The Ready? Set? Go! construct summarizes our findings well. We observed that the participating PCNs were in a favourable position to adopt the 2 interventions successfully. We implemented strategies to promote adoption (Ready), and respondents reported prioritization and willingness to initiate the interventions based on positive indicators (Set). Regardless, the interplay of organizational stability, leadership support, existing physician culture and organizational context influenced the overall degree of adoption of the interventions across the PCNs (Go). CONCLUSIONS: Our findings suggest that implementation of quality-improvement interventions into settings similar to the PCNs we studied will have the greatest likelihood of success when there is priority alignment, genuine and sustained leadership support and an innovative organizational culture. However, the stability of organizations may affect the degree to which staff can adopt quality-improvement interventions successfully, so organizational stability should be assessed on an ongoing basis. PMID- 26145484 TI - Comparing effectiveness of generic and disease-specific self-management interventions for people with diabetes in a practice context. AB - BACKGROUND: The effectiveness of self-management interventions has been demonstrated. However, the benefits of generic vs. disease-specific programs are unclear, and their efficacy within a practice setting has yet to be fully explored. OBJECTIVE: To compare the outcomes of the diabetes-specific self management program (Diabetes) and the generic chronic disease Self-management Program (Chronic Condition) and to explore whether program characteristics, evaluated using the Quality Self-Management Assessment Framework (Q-SAF), provide insight into the results of the outcome evaluation. METHODS: A pragmatic pretest, post-test design with 12-week follow up was used to compare the 2 self-management interventions. Outcomes were quality of life, self-efficacy, loneliness, self management skills, depression, and health behaviours. People with diabetes self selected attendance at the Diabetes or Chronic Condition program offered as part of routine practice. RESULTS: Participants with diabetes in the 2 programs (Diabetes=200; Chronic Condition=90) differed significantly in almost all demographic and clinical characteristics. Both programs yielded positive outcomes. Controlling for baseline and demographic characteristics, random effects modelling showed an interaction between time and program for 1 outcome: self-efficacy (p=0.029). Participants in the Chronic Condition group experienced greater improvements over time than did those in the Diabetes group. The Q-SAF analysis showed differences in program content, delivery and workforce capacity. CONCLUSIONS: People with diabetes benefited from both programs, but participation in the generic program resulted in greater improvements in self-efficacy for participants who had self-selected that program. Both programs in routine care led to health-related improvements. The Q-SAF can be used to assess the quality of programs. PMID- 26145485 TI - Challenges in Identifying Patients with Type 2 Diabetes for Quality-Improvement Interventions in Primary Care Settings and the Importance of Valid Disease Registries. AB - OBJECTIVE: Patient registries are considered an important foundation of chronic disease management, and diabetes patient registries are associated with better processes and outcomes of care. The purpose of this article is to describe the development and use of registries in the Alberta's Caring for Diabetes (ABCD) project to identify and reach target populations for quality-improvement interventions in the primary care setting. METHODS: We applied the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework and expanded the definition of reach beyond the individual (i.e. patient) level to include the ability to identify target populations at an organizational level. To characterize reach and the implementation of registries, semistructured interviews were conducted with key informants, and a usual-care checklist was compiled for each participating Primary Care Network (PCN). Content analysis was used to analyze qualitative data. RESULTS: Using registries to identify and recruit participants for the ABCD interventions proved challenging. The quality of the registries depended on whether physicians granted PCN access to patient lists, the strategies used in development, the reliability of diagnostic information and the data elements collected. In addition, once a diabetes registry was developed, there was limited ability to update it. CONCLUSIONS: Proactive management of chronic diseases like diabetes requires the ability to reach targeted patients at the population level. We observed several challenges to the development and application of patient registries. Given the importance of valid registries, strong collaborations and novel strategies that involve policy makers, PCNs and providers are needed to help find solutions to improve registry quality and resolve maintenance issues. PMID- 26145486 TI - Testing the assumption in ergonomics software that overall shoulder strength can be accurately calculated by treating orthopedic axes as independent. AB - To predict shoulder strength, most current ergonomics software assume independence of the strengths about each of the orthopedic axes. Using this independent axis approach (IAA), the shoulder can be predicted to have strengths as high as the resultant of the maximum moment about any two or three axes. We propose that shoulder strength is not independent between axes, and propose an approach that calculates the weighted average (WAA) between the strengths of the axes involved in the demand. Fifteen female participants performed maximum isometric shoulder exertions with their right arm placed in a rigid adjustable brace affixed to a tri-axial load cell. Maximum exertions were performed in 24 directions, including four primary directions, horizontal flexion-extension, abduction-adduction, and at 15 degrees increments in between those axes. Moments were computed and comparisons made between the experimentally collected strengths and those predicted by the IAA and WAA methods. The IAA over-predicted strength in 14 of 20 non-primary exertions directions, while the WAA underpredicted strength in only 2 of these directions. Therefore, it is not valid to assume that shoulder axes are independent when predicting shoulder strengths between two orthopedic axes, and the WAA is an improvement over current methods for the posture tested. PMID- 26145482 TI - The effect of social functioning and living arrangement on treatment intent, specialist assessment and treatment uptake for hepatitis C virus infection among people with a history of injecting drug use: The ETHOS study. AB - BACKGROUND: The objective was to assess social functioning and its association with treatment intent, specialist assessment and treatment uptake for hepatitis C virus (HCV) infection among people with a history of injecting drug use. METHODS: ETHOS is a prospective observational cohort evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from nine community health centres and opioid substitution treatment clinics (NSW, Australia). Social functioning was assessed using a short form of the Opioid Treatment Index social functioning scale. Those classified in the highest quartile (score >6) were considered having lower social functioning. Analyses were performed using logistic regression. RESULTS: Among 415 participants (mean age 41 years, 71% male), 24% were considered having lower social functioning, 70% had early HCV treatment intent (intention to be treated in the next 12 months), 53% were assessed by a specialist and 27% initiated treatment. Lower social functioning was independently associated with unemployment, unstable housing, recent injecting drug use and moderate to extremely severe symptoms of depression, anxiety and stress. Lower social functioning was independently associated with reduced early HCV treatment intent (aOR 0.51, 95% CI 0.30-0.84) and lower specialist assessment (aOR 0.48, 95% CI 0.29-0.79), but not HCV treatment uptake (aOR 0.76, 95% CI 0.40-1.43). Living with someone was independently associated with HCV treatment uptake (with someone and children: aOR 2.28, 95% CI 1.01-5.14; with someone and no children: aOR 2.36, 95% CI 1.30-4.31), but not early HCV treatment intent or specialist assessment. CONCLUSIONS: This study highlights the need for the development and implementation of strategies targeting people who inject drugs with lower social functioning to enhance HCV treatment intent and specialist assessment. Further, strategies to enhance social support may play a role in increasing HCV treatment uptake. PMID- 26145487 TI - Biomarkers of treatment outcome in schizophrenia: Defining a benchmark for clinical significance. AB - Emerging data from on imaging and genetic studies have generated interest in "clinically significant" biomarkers to predict response and prognosis. What constitutes "clinical significance" and how a biomarker would reach that threshold are unclear. To develop a benchmark we reviewed different approaches for defining "clinical significance" applied in schizophrenia research and identified that an improvement of 15 points on the PANSS Total is considered meaningful in clinical settings. Using this benchmark and we simulated thousands of schizophrenia trials, using characteristics derived from the NEWMEDS database with over 8000 patients with schizophrenia, to the kind of imaging, genetic, and other biomarkers that could attain clinical significance. We plotted the interaction between frequency-of-occurrence, the effect size of biomarkers and their relationship to the clinical significance threshold. Results show that categorical biomarkers are likely to attain clinical significance when they occur in 20-50% of the clinical population, and can predict at least a 8-10 point PANSS scale difference. Genetic markers are likely to have clinical significance when they occur in 20-50% of the population and can predict 7-9 points on the PANSS scale. A marker with a lower frequency or lesser effect size would find it hard to meet clinical significance thresholds for schizophrenia. The assumptions and limitations of this approach are discussed. Compared with standards in the rest of medicine, biomarkers that can attain this benchmark will be cost-effective and are likely to be adopted by clinical systems. PMID- 26145488 TI - Assessing the trend of HIV/AIDS mortality rate in Asia and North Africa: an application of latent growth models. AB - Over the last 30 years, HIV/AIDS has emerged as a major global health challenge. This study evaluates the change of HIV/AIDS mortality rates in Asian and North African countries from 1990 to 2010 using the Global Burden of Disease (GBD) study. HIV/AIDS mortality rates were derived from the GBD database from 1990 to 2010, for 52 countries in Asia and North Africa. First, a Latent Growth Model was employed to assess the change in AIDS mortality rate over time in six different regions of Asia, and also the change in AIDS mortality rate over time for males and females in Asia and North Africa. Finally, Latent Growth Mixture Models (LGMMs) were applied to identify distinct groups in which countries within each group have similar trends over time. Our results showed that increase in mortality rate over time for males is about three times greater than for females. The highest and lowest trend of AIDS mortality rates were observed in South-East Asia and high-income Asia-Pacific regions, respectively. The LGMM allocated most countries in the South and South-East region into two classes with the highest trend of AIDS mortality rates. Although the HIV/AIDS mortality rates are decreasing in some countries and clusters, the general trend in the Asian continent is upwards. Therefore, it is necessary to provide programmes to achieve the goal of access to HIV prevention measures, treatment, care, and support for high-risk groups, especially in countries with a higher trend of AIDS mortality rates. PMID- 26145489 TI - Individualized feedback-based virtual reality exercise improves older women's self-perceived health: a randomized controlled trial. AB - OBJECTIVES: Individualized feedback-based virtual reality (IFVR) exercise is gaining attention as a cost-effective self-management strategy, however little is known about whether older adults themselves perceive IFVR exercise effective in improving their health. Therefore, we studied the effect of IFVR exercise on health-related quality of life (HRQoL) in older women. METHODS: Fifty-four older women aged >=65 years were randomized to either IFVR exercise group (IFVRG, n=26) or group-based exercise group (GG, n=28). Both groups received a 60-min intervention three times a week for eight weeks. The Short-Form Health Survey (SF 36) was administered. To identify the possible placebo effect, 30-Second Chair Stand Test (30SCST), 8-Foot Up-and-Go Test (8FUGT), and 2-Minute Step Test (2MST) were also administered. RESULTS: intention-to-treat analysis with adjustment for baseline levels revealed that IFVRG showed greater improvement in mental health (p=0.029) and lower body strength (p=0.042), compared to GG. Within-group analysis for HRQoL revealed that IFVRG showed an increase in role-physical (p=0.015), bodily pain (p=0.017), general health (p=0.004), vitality (p=0.010), role-emotional (p=0.007), and mental health (p<0.001), whereas GG showed an increase in role-physical (p=0.022), general health (p=0.023), and social functioning (p = 0.023). Both groups showed an increase in 30SCST, 2MST and 8FUGT (all p<0.001). CONCLUSION: IFVR exercise improved HRQoL in older women, in addition to improving physical fitness. Therefore, it might be recommended to older women as an effective self-management strategy. PMID- 26145506 TI - Comparative morpho-physiology of the metapleural glands of two Atta leaf-cutting ant queens nesting in clayish and organic soils. AB - Queens of leaf-cutting ants found their nests singly, each consisting of a vertical tunnel and a final horizontal chamber. Because of the claustral mode of nest founding, the queen and/or her initial fungus garden are exposed to threats imposed by several soil pathogens, and the antibiotic secretions produced by their metapleural glands are considered a main adaptation to deal with them. Nests of two Atta leaf-cutting ant species, Atta vollenweideri and Atta sexdens rubropilosa, occur in different soil types, alfisols and oxisols. Their queens are known to excavate the initial nest in different soil horizons, clayish and organic, respectively, which differ in their fertility and associated microbiota. The aim of the present study was to comparatively investigate the morpho physiology of the metapleural glands in queens of A. vollenweideri and A. sexdens rubropilosa, addressing the question whether the distinct selective pressure imposed by the microbiota in the two different soil types led to morpho physiological differences in the metapleural glands that were consistent with their antiseptic function. The results revealed that metapleural glands of A. sexdens rubropilosa have a larger number of secretory cells, and consequently a higher production of antibiotic secretions, which may have been selected to allow nest founding at the superficial horizon of oxisols rich in organic matter and microorganisms. Glands of A. vollenweideri, on the contrary, presented fewer secretory cells, suggesting less production of antibiotic secretions. We argue that the excavation of deep founding nests in A. vollenweideri was primarily selected for during evolution to avoid the risk posed by flooding, and further hypothesize that a reduced number of cells in their metapleural glands occurred because of a weak pathogen-driven selective pressure at the preferred soil depth. PMID- 26145507 TI - Predicting the impact of biochar additions on soil hydraulic properties. AB - Different physical and chemical properties of biochar, which is made out of a variety of biomass materials, can impact water movement through amended soil. The objective of this research was to develop a decision support tool predicting the impact of biochar additions on soil saturated hydraulic conductivity (Ksat). Four different kinds of biochar were added to four different textured soils (coarse sand, fine sand, loam, and clay texture) to assess these effects at the rates of 0%, 1%, 2%, and 5% (w/w). The Ksat of the biochar amended soils were significantly influenced by the rate and type of biochar, as well as the original particle size of soil. The Ksat decreased when biochar was added to coarse and fine sands. Biochar with larger particles sizes (60%; >1 mm) decreased Ksat to a larger degree than the smaller particle size biochar (60%; <1 mm) in the two sandy textured soils. Increasing tortuosity in the biochar amended sandy soil could explain this behavior. On the other hand, for the clay loam 1% and 2% biochar additions universally increased the Ksat with higher biochar amounts providing no further alterations. The developed model utilizes soil texture pedotransfer functions for predicting agricultural soil Ksat as a function of soil texture. The model accurately predicted the direction of the Ksat influence, even though the exact magnitude still requires further refinement. This represents the first step to a unified theory behind the impact of biochar additions on soil saturated conductivity. PMID- 26145508 TI - Effect of stimulation with a gonadotropin mixture on reproductive outcome in nulliparous ewes bred during seasonal anestrus and early breeding season. AB - To evaluate the effect of gonadotropic stimulation on the reproductive response of nulliparous acyclic female sheep during mid-anestrous and early breeding season, fall-born ewe lambs of mixed breeding (N=191; ~7 months old; study 1) and yearlings (Dorset X Texel (DT), N=120, study 2) were assigned randomly during May to July to be either pre-treated with progesterone using CIDR-g (0.3g of progesterone) devices for 5 days or to also receive gonadotropins (240IU eCG and 120IU hCG, 3mL i.m. injection of P.G. 600((r))) at CIDR-g removal. Study 3 was conducted with nulliparous acyclic DT yearling ewes (N=104) in late August and was similar to study 2 except that a group of control ewes that were not treated was included. Gonadotropic stimulation increased estrous response (P=0.0002), pregnancy rate to the first service period (P=0.0007), proportion of ewes lambing (P=0.03) and the lambing rate (P=0.01) in fall-born ewe lambs (study 1), but did not modify reproductive outcome in yearling females (study 2) during mid anestrus. During the transition into the breeding season (study 3), progesterone pre-treatment increased the pregnancy rate and the proportion of ewes lambing to first service after ram introduction (P=0.003 and P=0.02, respectively). However, gonadotropic stimulation of progesterone pre-treated yearlings did not modify reproductive performance variables. In conclusion, gonadotropic stimulation improved reproductive outcome in fall-born ewe lambs bred during the mid anestrous period, but did not affect reproductive outcome in yearling females. PMID- 26145509 TI - Interaction of endokinin A/B and (Mpa(6))-gamma2-MSH-6-12 in pain regulation in mice. AB - The present study focused on the interactive effects of (Mpa(6))-gamma2-MSH-6-12 (Mpa, spinal level) and endokinin A/B (EKA/B, supraspinal level) on pain regulation in mice. EKA/B (30 pmol) only weakened 100 pmol Mpa-induced hyperalgesia at 5 min, but could enhance it during 20-30 min. However, EKA/B (100 pmol) antagonized all dose levels of Mpa significantly at 5 min and blocked them completely at 10 min. EKA/B (3 nmol) co-injected with Mpa presented marked analgesia at 5 min and enduring hyperalgesia within 20-60 min. To investigate the underlying mechanisms between Mpa and EKA/B, SR140333B and SR142801 (NK1 and NK3 receptor antagonists, respectively) were utilized. SR140333B had no influence on Mpa, while SR142801 potentiated it during 20-30 min. Whereas, SR140333B and SR142801 could block the co-administration of Mpa and EKA/B (30 pmol) separately at 5 min and 30 min. These phenomena might attribute to that these two antagonists promoted the antagonism of EKA/B (30 pmol) at the early stage, while antagonized EKA/B preferentially in the latter period. SR140333B weakened the analgesia of EKA/B (3 nmol), but produced no effect on Mpa. However, SR140333B failed to affect the co-injection of Mpa and EKA/B, which implied that EKA/B cooperated with Mpa prior to SR140333B. These results could potentially help to better understand the interaction of NK and MrgC receptors in pain regulation in mice. PMID- 26145510 TI - A Novel pseudo-Four-Component Domino Reaction for the Synthesis of Naphtho[2,1 b]furan-2(1H)-ones Using a Nanocatalyst. AB - In this article, an original one-pot method is utilized to synthesize a variety of derivatives of naphtho[2,1-b]furan-2(1H)-one via a pseudo-four-component domino reaction of aryl aldehydes, acetic anhydride, hippuric acids, and 2 naphthols catalyzed by HSW@SPIONs. This reaction illustrates an array of attractive features including, with particular interest in this report, a convenient and unique process of creating and utilizing a powerful recyclable nanocatalyst. PMID- 26145511 TI - Iso-Oriented Anatase TiO2 Mesocages as a High Performance Anode Material for Sodium-Ion Storage. AB - A major obstacle in realizing Na-ion batteries (NIBs) is the absence of suitable anode materials. Herein, we firstly report the anatase TiO2 mesocages constructed by crystallographically oriented nanoparticle subunits as a high performance anode for NIBs. The mesocages with tunable microstructures, high surface area (204 m(2) g(-1)) and uniform mesoporous structure were firstly prepared by a general synthesis method under the assist of sodium dodecyl sulfate (SDS). It's notable that the TiO2 mesocages exhibit a large reversible capacity and good rate capability. A stable capacity of 93 mAhg(-1) can be retained after 500 cycles at 10 C in the range of 0.01-2.5 V, indicating high rate performance and good cycling stability. This could be due to the uniform architecture of iso-oriented mesocage structure with few grain boundaries and nanoporous nature, allowing fast electron and ion transport, and providing more active sites as well as freedom for volume change during Na-ion insertion. CV measurements demonstrate that the sodium-ion storage process of anatase mesocages is mainly controlled by pseudocapacitive behavior, which is different from the lithium-ion storage and further facilitates the high rate capability. PMID- 26145529 TI - Cancer proteomics: developments in technology, clinical use and commercialization. AB - In the last two decades, advances in genomic, transcriptomic and proteomic methods have enabled us to identify and classify cancers by their molecular profiles. Many anticipate that a molecular taxonomy of cancer will not only lead to more effective subtyping of cancers but also earlier diagnoses, more informative prognoses and more targeted treatments. This article reviews recent technological developments in the field of proteomics, recent discoveries in proteomic cancer biomarker research and trends in clinical use. Readers are also informed of examples of successful commercialization, and the future of proteomics in cancer diagnostics. PMID- 26145530 TI - The effect of femoral tunnel widening on one-year clinical outcome after anterior cruciate ligament reconstruction using ZipLoop(r) technology for fixation in the cortical bone of the femur. AB - BACKGROUND: The effect of femoral tunnel widening on clinical outcomes of anterior cruciate ligament (ACL) reconstruction has been rarely investigated. In this study, ACL reconstructions were performed using semitendinosus and gracilis (STG) tendon grafts and single cortical fixation on the femoral side. The aim was to analyze femoral tunnel widening at one year and to evaluate its effect on clinical and laximetric outcomes. METHODS: A total of 46 patients were enrolled in this prospective continuous single-operator monocenter study. Clinical protocol included pre-operative and one-year evaluation with subjective and objective International Knee Documentation Committee (IKDC) clinical scores. Computed tomography (CT) scan was used for radiographic examination during the follow-up period. The femoral tunnel widening was measured as a three-dimensional (3D) image using OsiriX software. The cross-sectional area of each tunnel was measured at four different locations. RESULTS: The subjective preoperative IKDC score was 50 and one-year postoperative score was 81.8. The side-to-side difference in knee laxity decreased from 2.94 to 0.74 mm. The objective IKDC score during the final follow-up was rated A in 27 patients and B in 17. CT scan data revealed an average of 49.32% cone-shaped widening of the femoral tunnel. Femoral tunnel widening at the level of the joint (F4) was negatively correlated with the IKDC subjective score at one year. CONCLUSIONS: This study revealed a significant widening of the femoral tunnel by demonstrating its conical shape at one year post-surgery. A significant correlation could be established between femoral tunnel widening close to the joint and IKDC scores. PMID- 26145531 TI - [Analgesic efficacy of the ultrasound-guided blockade of the transversus abdominis plane - a systematic review]. AB - BACKGROUND: The transverse abdominal plan blockade (TAP) is a block of abdominal wall that has diffused rapidly in the clinical practice as part of a multimodal analgesia for abdominal surgery. The performance of the ultrasound-guided technique has allowed the lowering of potential complications, as well as new approaches that according to the descriptions carried out and the prospective studies would make it possible to utilize the TAP in different surgical interventions; however, the results obtained in randomized clinical trials (RCTs) are inconsistent. OBJECTIVES: To prepare a systematic review aiming to determine the efficacy of the ultrasound-guided TAP for different surgical interventions, as well as the indications according to the approaches and their influences. METHODS: Two research approaches, one manual, and the other in Pubmed returned 28 RCT where an intervention with ultrasound-guided TAP were performed to compare the analgesic efficacy in contrast to another technique in adults, published between 2007 and October 2013, in English or Spanish, with Jadad score > 1, according to the inclusion criteria for this review. The authors analyzed independently all the RCT. CONCLUSIONS: The TAP have been shown to be an effective technique in colorectal surgery, cesarean section, cholecystectomy, hysterectomy, appendectomy, donor nephrectomy, retropubic prostatectomy, and bariatric surgery. However, the data found in RCT are not conclusive, and as a result, it is necessary to develop new and well designed RCT, with enough statistical power to compare different approaches, drugs, doses, and volumes for the same intervention, aiming to answer the current questions and their effects in the habitual clinical practice. PMID- 26145532 TI - Motivational enhancement therapy in obese patients: A promising application. AB - A pilot uncontrolled study aimed at investigating the efficacy of a motivational enhancement therapy adapted for obesity was conducted on 71 obese patients (59 females). Treatment consisted of 5 weekly group sessions and 3 weekly individual sessions. Outcome measures included Treatment, Motivation and Readiness test (TREMORE) and anthropometric measures. Patients showed a significant reduction of all anthropometric parameters (with exception of waist circumference), and a significant improvement of TREMORE scores at the end of the treatment. The motivational interviewing program applied in the current study appears to be effective and consistent with both patient recommendations and health care clinic demands. PMID- 26145533 TI - miR-204 mediates post-transcriptional down-regulation of PHOX2B gene expression in neuroblastoma cells. AB - Neuroblastoma (NB) is a rare childhood cancer of the peripheral sympathetic nervous system and accounts for approximately 10% of all pediatric tumors. Heterozygous PHOX2B mutations have been found in association with NB development in familial, sporadic and syndromic cases. In addition, the PHOX2B gene is widely over-expressed both in tumor samples and NB cell lines. Post-transcriptional gene regulation is known to be involved in mRNA stability and, in NB, microRNAs (miRNAs) seem to be responsible for altered expression of genes driving differentiation, apoptosis, and migration. To assess the possible impact of post transcriptional regulation in NB cell lines, we have focused on the PHOX2B mRNA stability by both in silico analysis and functional studies on its 3'untranslated region (3'UTR). PHOX2B gene expression has resulted under post-transcriptional control, as suggested by: i) instability of PHOX2B mRNA, demonstrated by short mRNA half-life levels in both IMR32 and LAN-1 cell lines, ii) role of the PHOX2B 3'UTR, confirmed by the activity of proper reporter constructs, and iii) miRNA 204, shown to enhance the PHOX2B 3'UTR mediated down-regulation of the reporter construct activity. Finally, miRNA-204 has resulted to decrease the stability of the PHOX2B mRNA at different extents in the presence of different SNP rs1063611 alleles. Therefore, post-transcriptional down-regulation of the PHOX2B gene takes place in NB cell lines and miRNA-204 participates in such a 3'UTR mediated control. PMID- 26145551 TI - High fat diet impairs the function of glucagon-like peptide-1 producing L-cells. AB - Glucagon-like peptide-1 (GLP-1) acts as a satiety signal and enhances insulin release. This study examined how GLP-1 production from intestinal L-cells is modified by dietary changes. METHODS: Transgenic mouse models were utilized in which L-cells could be purified by cell specific expression of a yellow fluorescent protein, Venus. Mice were fed on chow or 60% high fat diet (HFD) for 2 or 16 weeks. L-cells were purified by flow cytometry and analysed by microarray and quantitative RT-PCR. Enteroendocrine cell populations were examined by FACS analysis, and GLP-1 secretion was assessed in primary intestinal cultures. RESULTS: Two weeks HFD reduced the numbers of GLP-1 positive cells in the colon, and of GIP positive cells in the small intestine. Purified small intestinal L cells showed major shifts in their gene expression profiles. In mice on HFD for 16 weeks, significant reductions were observed in the expression of L-cell specific genes, including those encoding gut hormones (Gip, Cck, Sct, Nts), prohormone processing enzymes (Pcsk1, Cpe), granins (Chgb, Scg2), nutrient sensing machinery (Slc5a1, Slc15a1, Abcc8, Gpr120) and enteroendocrine-specific transcription factors (Etv1, Isl1, Mlxipl, Nkx2.2 and Rfx6). A corresponding reduction in the GLP-1 secretory responsiveness to nutrient stimuli was observed in primary small intestinal cultures. CONCLUSION: Mice fed on HFD exhibited reduced expression in L-cells of many L-cell specific genes, suggesting an impairment of enteroendocrine cell function. Our results suggest that a western style diet may detrimentally affect the secretion of gut hormones and normal post prandial signaling, which could impact on insulin secretion and satiety. PMID- 26145564 TI - A New Phospholipase A2 from Lachesis muta rhombeata: Purification, Biochemical and Comparative Characterization with Crotoxin B. AB - Phospholipases A2 (PLA2s) are enzymes responsible for inflammatory effects, edema formation, myotoxicity, neurotoxicity and other manifestations from envenoming. In this paper we report the isolation and biochemical characterization of Lmr PLA2, the first acidic PLA2 found in Lachesis muta rhombeata venom. Furthermore, this study compared biological effects of Lmr-PLA2 and crotoxin B (CB), a PLA2 from Crotalus durissus terrificus venom. Lmr-PLA2 was isolated by molecular exclusion and reversed phase chromatography. The purified enzyme showed a molecular mass of 13,975 Da, pI of 5.46 and its partial amino acid sequence showed a high identity with PLA2s already described in the literature. In addition, this enzyme possesses the residue D49 in its amino acid sequence, indicating that it is a catalytically active PLA2. Lmr-PLA2 presented high phospholipase activity and was able to inhibit platelet aggregation. Studies of biochemical characterization of new PLA2s, as Lmr-PLA2, are relevant since they help to clarify the structure-function relationship of this important class of toxins. PMID- 26145565 TI - Sex hormones affect language lateralisation but not cognitive control in normally cycling women. AB - This article is part of a Special Issue "Estradiol and Cognition". Natural fluctuations of sex hormones during the menstrual cycle have been shown to modulate language lateralisation. Using the dichotic listening (DL) paradigm, a well-established measurement of language lateralisation, several studies revealed that the left hemispheric language dominance was stronger when levels of estradiol were high. A recent study (Hjelmervik et al., 2012) showed, however, that high levels of follicular estradiol increased lateralisation only in a condition that required participants to cognitively control (top-down) the stimulus-driven (bottom-up) response. This finding suggested that sex hormones modulate lateralisation only if cognitive control demands are high. The present study investigated language lateralisation in 73 normally cycling women under three attention conditions that differed in cognitive control demands. Saliva estradiol and progesterone levels were determined by luminescence immunoassays. Women were allocated to a high or low estradiol group. The results showed a reduced language lateralisation when estradiol and progesterone levels were high. The effect was independent of the attention condition indicating that estradiol marginally affected cognitive control. The findings might suggest that high levels of estradiol especially reduce the stimulus-driven (bottom-up) aspect of lateralisation rather than top-down cognitive control. PMID- 26145566 TI - Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions. AB - This article is part of a Special Issue "SBN 2014". Obesity in women of child bearing age is a growing problem in developed and developing countries. Evidence from human studies indicates that maternal BMI correlates with offspring adiposity from an early age and predisposes to metabolic disease in later life. Thus the early life environment is an attractive target for intervention to improve public health. Animal models have been used to investigate the specific physiological outcomes and mechanisms of developmental programming that result from exposure to maternal obesity in utero. From this research, targeted intervention strategies can be designed. In this review we summarise recent progress in this field, with a focus on cardiometabolic disease and central control of appetite and behaviour. We highlight key factors that may mediate programming by maternal obesity, including leptin, insulin, and ghrelin. Finally, we explore potential lifestyle and pharmacological interventions in humans and the current state of evidence from animal models. PMID- 26145578 TI - Structural and biochemical insights into the degradation mechanism of chitosan by chitosanase OU01. AB - BACKGROUND: A detailed knowledge about the degradation mechanism of chitosanase hydrolysis is critical for the design of novel enzymes to produce well-defined chito-oligosaccharide products. METHODS: Through the combination of structural and biochemical analysis, we present new findings that provide novel insights into the degradation mechanism of chitosanase OU01. RESULTS: We have determined the crystal structure of Asp(43)/Ala mutant of OU01, and have trapped the hydrolyzed product of the reaction. This structure reveals the role of the general acid (Glu(25)) in catalysis. Two structural features about the mechanisms of the non-processive chitosanases are described for the first time. 1). Structural comparison reveals that the enzyme goes through an open-closed-open conformational transition upon substrate binding and product release; 2). polar residues constitute the substrate binding cleft. Additional site important for polymeric substrate recognition is identified and a three-step polymeric substrate recognition mechanism is proposed. CONCLUSIONS: Detailed substrate recognition mechanism is described for non-processive chitosanase for the first time. GENERAL SIGNIFICANCE: These findings provide new structural insights into the understanding of overall hydrolysis mechanism for non-processive chitosanase, and also will facilitate the design of new enzymes used for industrial purpose. PMID- 26145577 TI - Differences in solution dynamics between lens beta-crystallin homodimers and heterodimers probed by hydrogen-deuterium exchange and deamidation. AB - BACKGROUND: Lens transparency is due to the ordered arrangement of the major structural proteins, called crystallins. betaB2 crystallin in the lens of the eye readily forms dimers with other beta-crystallin subunits, but the resulting heterodimer structures are not known and were investigated in this study. METHODS: Structures of betaA3 and betaB2 crystallin homodimers and the betaA3/betaB2 crystallin heterodimers were probed by measuring changes in solvent accessibility using hydrogen-deuterium exchange with mass spectrometry. We further mimicked deamidation in betaB2 and probed the effect on the betaA3/betaB2 heterodimer. Results were confirmed with chemical crosslinking and NMR. RESULTS: Both betaA3 and betaB2 had significantly decreased deuterium levels in the heterodimer compared to their respective homodimers, suggesting that they had less solvent accessibility and were more compact in the heterodimer. The compact structure of betaB2 was supported by the identification of chemical crosslinks between lysines in betaB2 within the heterodimer that were inconsistent with betaB2's extended homodimeric structure. The compact structure of betaA3 was supported by an overall decrease in mobility of betaA3 in the heterodimer detected by NMR. In betaB2, peptides 70-84 and 121-134 were exposed in the homodimer, but buried in the heterodimer with >=50% decreases in deuterium levels. Homologous peptides in betaA3, 97-109 and 134-149, had 25-50% decreases in deuterium levels in the heterodimer. These peptides are probable sites of interaction between betaB2 and betaA3 and are located at the predicted interface between subunits with bent linkers. Deamidation at Q184 in betaB2 at this predicted interface led to a less compact betaB2 in the heterodimer. The more compact structure of the betaA3/betaB2 heterodimer was also more heat stable than either of the homodimers. CONCLUSIONS: The major structural proteins in the lens, the beta-crystallins, are not static, but dynamic in solution, with differences in accessibility between the homo-and hetero-dimers. This structural flexibility, particularly of betaB2, may facilitate formation of different size higher-ordered structures found in the transparent lens. GENERAL SIGNIFICANCE: Understanding complex hetero-oligomer interactions between beta-crystallins in normal lens and how these interactions change during aging is fundamental to understanding the cause of cataracts. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. PMID- 26145579 TI - Protein-RNA and protein-glycan recognitions in light of amino acid codes. AB - BACKGROUND: RNA-binding proteins, in cooperation with non-coding RNAs, play important roles in post-transcriptional regulation. Non-coding micro-RNAs control information flow from the genome to the glycome by interacting with glycan synthesis enzymes. Glycan-binding proteins read the cell surface and cytoplasmic glycome and transfer signals back to the nucleus. The profiling of the protein RNA and protein-glycan interactomes is of significant medicinal importance. SCOPE OF REVIEW: This review discusses the state-of-the-art research in the protein-RNA and protein-glycan recognition fields and proposes the application of amino acid codes in profiling and programming the interactomes. MAJOR CONCLUSIONS: The deciphered PUF-RNA and PPR-RNA amino acid recognition codes can be explained by the protein-RNA amino acid recognition hypothesis based on the genetic code. The tripartite amino acid code is also involved in protein-glycan interactions. At present, the results indicate that a system of four codons ("gnc", where n=g - guanine, c - cytosine, u - uracil or a - adenine) and four amino acids (G - glycine, A - alanine, V - valine, D - aspartic acid) could be the original genetic code that imprinted "rules" into both recognition processes. GENERAL SIGNIFICANCE: Amino acid recognition codes have provocative potential in the profiling and programming of the protein-RNA and protein-glycan interactomes. The profiling and even programming of the interactomes will play significant roles in diagnostics and the development of therapeutic procedures against cancer and neurodegenerative, developmental and other diseases. PMID- 26145580 TI - Ca2+ and betagamma-crystallins: An affair that did not last? AB - BACKGROUND: During the last three decades, lens beta- and gamma-crystallins have found a huge number of kin from numerous taxonomical sources. Most of these proteins from invertebrates and microbes have been demonstrated or predicted to bind Ca2+ involving a distinct double-clamp motif, which is largely degenerated in lens homologues. SCOPE OF REVIEW: The various aspects of transformation of betagamma-crystallins from a quintessential Ca2+-binding protein into a primarily structural molecule have been reviewed. MAJOR CONCLUSIONS: In lens members of betagamma-crystallins, the residues involved in Ca2+ binding have diverged considerably from the classical consensus with consequent reduction in their Ca2+ binding properties. This evolutionary change is congenial to their new role as robust constituents of lens. The exact functions of the residual affinity for Ca2+ are yet to be established. GENERAL SIGNIFICANCE: This review highlights the significance of reduction in Ca2+-binding ability of the betagamma-crystallins for lens physiology and why this residual affinity may be functionally important. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. PMID- 26145581 TI - Applying Lean methodologies reduces ED laboratory turnaround times. AB - BACKGROUND: Increasing the value of health care delivery is a national priority, and providers face growing pressure to reduce cost while improving quality. Ample opportunity exists to increase efficiency and quality simultaneously through the application of systems engineering science. OBJECTIVE: We examined the hypothesis that Lean-based reorganization of laboratory process flow would improve laboratory turnaround times (TAT) and reduce waste in the system. METHODS: This study was a prospective, before-after analysis of laboratory process improvement in a teaching hospital emergency department (ED). The intervention included a reorganization of laboratory sample flow based in systems engineering science and Lean methodologies, with no additional resources. The primary outcome was the median TAT from sample collection to result for 6 tests previously performed in an ED kiosk. RESULTS: After the intervention, median laboratory TAT decreased across most tests. The greatest decreases were found in "reflex tests" performed after an initial screening test: troponin T TAT was reduced by 33 minutes (86 to 53 minutes; 99% confidence interval, 30-35 minutes) and urine sedimentation TAT by 88 minutes (117 to 29 minutes; 99% confidence interval, 87-90 minutes). In addition, troponin I TAT was reduced by 12 minutes, urinalysis by 9 minutes, and urine human chorionic gonadotropin by 10 minutes. Microbiology rapid testing TAT, a "control," did not change. CONCLUSIONS: In this study, Lean-based reorganization of laboratory process flow significantly increased process efficiency. Broader application of systems engineering science might further improve health care quality and capacity while reducing waste and cost. PMID- 26145582 TI - Use of intra-aortic balloon pump support for oozing-type cardiac rupture after acute myocardial infarction. AB - Left ventricular free wall rupture usually leads to acute hemopericardium and sudden cardiac death resulting in cardiac tamponade. Rarely, only a few patients with subacute free wall rupture such as oozing-type ventricular rupture or left ventricular false aneurysm may permit time for pericardiocentesis and surgery. We report a 63-year-old man with ST-elevation myocardial infarction who underwent primary percutaneous coronary intervention about 12 hours from the onset, and cardiac tamponade occurred on the second day. An intra-aortic balloon pump (IABP) was immediately inserted for hemodynamic support. After 100 mL of pericardial fresh blood was drained from the percardial cavity, his hemodynamic collapse was promptly improved with IABP support. In the following 24 hours, about 600 mL of hemorrhagic pericardial fluid was drained. The most likely diagnosis was concerning for oozing-type ventricular rupture, and a conservative approach was decided. The patient survived to the acute phase under IABP support and was discharged with complete recovery. PMID- 26145583 TI - An approach to markedly elevated blood pressure in hypertensive patients without acute organ damage. PMID- 26145584 TI - Emergency coronary angiography in out-of-hospital cardiac arrest patients without STEMI. AB - Current guideline recommends that immediate coronary angiography (CAG) should be considered in all postcardiac arrest patients in whom acute coronary syndrome is suspected. In the setting of out-of-hospital cardiac arrest (OHCA), obtaining clinical data such as chest discomfort and medical diseases associated with acute coronary syndrome can be difficult. Therefore, emergency physicians depend on electrocardiographic findings after return of spontaneous circulation (ROSC) when they have to decide whether emergency CAG should be performed. In clinical practice, the usefulness of emergency CAG evaluation of OHCA patients without ST segment elevation myocardial infarction is debatable. We describe 2 OHCA patients who did not exhibit ST-segment elevation after ROSC and received underwent emergency CAG. PMID- 26145585 TI - Cytotoxicity and antibacterial activity of a new generation of nanoparticle-based consolidants for restoration and contribution to the safe-by-design implementation. AB - Works of art are constantly under physical, chemical and biological degradation, so constant restoration is required. Consolidation is an important step in restoration, and traditional approaches and materials have already shown their limitations. To solve these problems, new nanoparticle-based consolidants were developed. No information on their toxicity is yet available. In this work, we focused our attention on potential risks posed by three commercially available nanoparticle-based consolidants: silica (SiO2 NPs), silanized silica (silanized SiO2 NPs) and calcium hydroxide (nanolime) nanoparticle dispersions. Occupational exposure impact was tested on three in vitro models mimicking inhalation, dermal contact and systemic routes. While no toxic effects were observed for nanolime and silanized SiO2 NPs, bare SiO2 NPs showed a dose- and time-dependent damage in all considered models. Corrosion test on EpiSkin(r) revealed no viability reduction. Works of art degradation is partially due to microorganism activity. Consolidant antibacterial activity was evaluated on three representative bacterial strains. Silica NPs-based consolidants showed effect on specific bacterial groups, while no specificity was observed with nanolime. In conclusion, silanized SiO2 NPs-based consolidant emerged as the safest and bacteriologically active product. The different biological impact of bare and silanized SiO2 NPs highlights the importance of safe-by-design approach in developing nanoparticle containing products. PMID- 26145586 TI - Translocation of positively and negatively charged polystyrene nanoparticles in an in vitro placental model. AB - To obtain insight in translocation of nanoparticles across the placental barrier, translocation was studied for one positively and two negatively charged polystyrene nanoparticles (PS-NPs) of similar size in an in vitro model. The model consisted of BeWo b30 cells, derived from a human choriocarcinoma grown on a transwell insert forming a cell layer that separates an apical from a basolateral compartment. PS-NPs were characterized with respect to size, surface charge, morphology and protein corona. Translocation of PS-NPs was not related to PS-NP charge. Two PS-NPs were translocated across the BeWo transwell model to a lower extent than amoxicillin, a model compound known to be translocated over the placental barrier to only a limited extent, whereas one PS-NP showed a slightly higher translocation. Studies on the effect of transporter inhibitors on the translocation of the PS-NPs indicated that their translocation was not mediated by known transporters and mainly dependent on passive diffusion. It is concluded that the BeWo b30 model can be used as an efficient method to get an initial qualitative impression about the capacity of NPs to translocate across the placental barrier and set priorities in further in vivo studies on translocation of NPs to the fetus. PMID- 26145601 TI - Stromal cell-derived factor-1 alpha alleviates hypoxic-ischemic brain damage in mice. AB - Hypoxic-ischemic brain damage (HIBD) is a major cause of acute deaths and chronic nervous system damage. There is good evidence that stromal cell-derived factor-1 alpha (SDF-1alpha) has been receiving much interest in its role in the treatment of ischemic diseases. Here we aim to investigate the effect of intraperitoneal delivery of SDF-1alpha after experimental hypoxia-ischemia (HI) and the potentially involved mechanisms. A total of 129 mice were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia, randomly assigned to three groups: sham, HI + vehicle and HI + SDF-1alpha. Mice treated with SDF-1alpha showed recovery of spatial learning abilities and pathological conditions, decreased number of apoptotic cells, and elevated expression of SDF-1alpha and its cognate receptor, CXC chemokine receptor-4 (CXCR4). Meanwhile, the increased number of mesenchymal stem cells (MSCs) was found in peripheral blood after SDF 1alpha treatment. Taken together, the treatment of SDF-1alpha after HIBD contributed to an improved functional recovery, and this behavioral restoration was paralleled by a reduction of apoptosis and mobilization of MSCs via SDF 1alpha/CXCR4. PMID- 26145684 TI - Influence of relative humidity on heterogeneous kinetics of NO2 on kaolin and hematite. AB - In order to obtain reliable kinetic parameters, it is required to measure the reaction kinetics of important heterogeneous reactions at ambient relative humidity (RH). In this study, the uptake coefficients and HONO yields for the heterogeneous reaction of NO2 on kaolin and hematite were measured at RH from 7% to 74% and at ambient pressure in the dark using a coated-wall flow tube reactor. The initial true uptake coefficient (gammat,ini) of NO2 at RH 7% was measured to be (1.44 +/- 0.10) * 10(-7) and (1.58 +/- 0.13) * 10(-6) on kaolin and hematite, respectively, while it decreased notably on both minerals, accompanied by an increase of HONO yields, as RH increased. The average gammat,ini at 32-74% RH was (4.42 +/- 1.17) * 10(-8) and (2.83 +/- 0.84) * 10(-7) on kaolin and hematite, respectively. The corresponding mean HONO yield was (36.0 +/- 16.1)% and (75.9 +/ 3.32)%, respectively. PMID- 26145685 TI - [Patient safety: vigilance and transparency]. PMID- 26145688 TI - [The nurse's role in the post-diagnosis consultation]. AB - The diagnosis of multiple sclerosis is major news, which is impossible for patients to receive while remaining calm and lucid. Even if the patients have anticipated the diagnosis, it still comes as a huge shock. A post-diagnosis consultation can be led by a nurse and/or a psychologist. PMID- 26145687 TI - [Multiple sclerosis : trends and management]. AB - Multiple sclerosis affects almost 100 000 people in France with a higher prevalence among women. It is the most common cause of non-traumatic disability in the young adult. Recent years have been marked by a better understanding of the physiopathology and risk factors, as well as by an increase in the number of available treatments. PMID- 26145689 TI - [Early hospital care of the patient with multiple sclerosis]. AB - The initial period in an MS patient's care is decisive. The priority is to establish a relationship of trust and to draw up an accurate assessment in order to create a personalised care plan. PMID- 26145690 TI - [The specialized multiple sclerosis networks, at the heart of the organization of patient planning]. AB - The SEP-Bretagne network draws on the skills of the health professionals involved with patients with Multiple sclerosis. It brings together medical and paramedical professionals, to support actions aimed at improving the care pathway and the quality of life of patients. PMID- 26145691 TI - [Knowing more about oneself to help one care for others]. AB - The onset of a disease such as multiple sclerosis is a profound existential trauma. The outlook of the disability is difficult to manage. Complementary approaches enable the caregivers to help the patients overcome difficulties and find ways to adapt. PMID- 26145692 TI - [Nursing consultation for sexual problems in multiple sclerosis]. AB - Patients with multiple sclerosis often complain of sexual problems. Nurses in a neurology department have decided to explore the sexual health of these patients. They also intend to assess the need for a neurosexuality nurse consultation. PMID- 26145693 TI - [Support from a non-profit organization to improve the quality of life of multiple sclerosis patients]. AB - For more than 50 years, the French Multiple Sclerosis Association has been bringing together people affected by this condition. A registered charity, it offers extensive social support to improve the daily lives of patients and their families at home or in a healthcare institution. PMID- 26145694 TI - [A nurse in a healthcare center in Guinea]. AB - For the last two years, Christine Damoisy has been working as a nurse in a rural healthcare centre in Guinea. Responsible for the management of the centre, helped by two assistant translators, she offers consultations, makes diagnoses with remote doctors, prescribes medication, guides patients, cares for wounds and gives advice. In this article she describes her practice. PMID- 26145695 TI - [Training can be fun!]. AB - Serious games are becoming ever more innovative and increasingly popular within the healthcare profession. Developed as a remote training tool, they support health professionals in a fun way, enabling them to update their knowledge and aptitude. This article looks at a serious game developed for nursing homes. PMID- 26145696 TI - [Foster the integration of the new arrivals]. AB - In care units, the turnover caused, in the teams, by the retirement of nurses and the mobility of the professionals, raises the risk of acquired experiential knowledge being lost. The passing on of knowledge to students, recent graduates or newly transferred staff, is therefore a priority. The unit nurse tutor organize it to ensure skills are retained in nursing care. PMID- 26145697 TI - [Welcoming a child of a parent hospitalized in intensive care]. AB - For a child, the hospitalisation of one of their parents in intensive care has a huge impact on family dynamics. The neurosurgical intensive care team at Rouen general hospital has consequently developed specific ways of enabling children in these situations to visit their parent. PMID- 26145698 TI - [Emergency nurse faced with death in pre-hospital situations]. AB - The occurrence of a death in the out-of-hospital environment is often brutal and the reactions of the deceased's family and friends, unprepared for this event, can be unpredictable. After the technical procedures have been carried out and within a limited period of intervention, the caregivers, and in particular the nurse of the mobile emergency and intensive care service, must provide the family and friends with support enabling them to begin the grieving process. To help the caregivers in this mission, a pedagogical tool remains to be developed. PMID- 26145699 TI - [Diabetes and quality of life]. PMID- 26145700 TI - [Nursing care of airway obstruction caused by food]. PMID- 26145701 TI - Preventive Dentistry and Oral Hygiene. AB - The biggest oral health campaign in the United Kingdom is called "National Smile Month" and it starts in May. For this occasion, the occupational medicine team of Kensington Hospital is holding special events highlighting preventive dentistry and oral hygiene. PMID- 26145702 TI - [Learning French sign language]. PMID- 26145703 TI - [Nurse's role in the diagnosis of onychomycosis]. PMID- 26145704 TI - Magnetic solid phase extraction coupled with desorption corona beam ionization mass spectrometry for rapid analysis of antidepressants in human body fluids. AB - Ambient ionization techniques show good potential in rapid analysis of target compounds. However, a direct application of these ambient ionization techniques for the determination of analytes in a complex matrix is difficult due to the matrix interference and ion suppression. To resolve this problem, here we developed a strategy by coupling magnetic solid phase extraction (MSPE) with desorption corona beam ionization (DCBI)-mass spectrometry (MS). As a proof of concept, the pyrrole-coated Fe3O4 magnetic nanoparticles (Fe3O4@Ppy) were prepared and used for the extraction of antidepressants. After extraction, the Fe3O4@Ppy with trapped antidepressants was then directly subjected to DCBI-MS analysis with the aid of a homemade magnetic glass capillary. As the MSPE process is rapid and the direct DCBI-MS analysis does not need solvent desorption or chromatographic separation processes, the overall analysis can be completed within 3 min. The proposed MSPE-DCBI-MS method was then successfully used to determine antidepressants in human urine and plasma. The calibration curves were obtained in the range of 0.005-0.5 MUg mL(-1) for urine and 0.02-1 MUg mL(-1) for plasma with reasonable linearity (R(2) > 0.951). The limits of detection of three antidepressants were in the range of 0.2-1 ng mL(-1) for urine and 2-5 ng mL(-1) for plasma. Acceptable reproducibility for rapid analysis was achieved with relative standard deviations less than 19.1% and the relative recoveries were 85.2-118.7%. Taken together, the developed MSPE-DCBI-MS strategy offers a powerful capacity for rapid analysis of target compounds in a complex matrix, which would greatly expand the applications of ambient ionization techniques with plentiful magnetic sorbents. PMID- 26145705 TI - Influence of Temperature on the Rotameric Forms of the Propyl Acetate Molecule: Raman and FTIR Spectroscopic Studies Aided by ab Initio and Car-Parrinello Molecular Dynamics Simulations. AB - The conformational preferences of the industrially and biologically significant propyl acetate (PA) molecule have been investigated by Raman and FTIR spectra, aided by ab initio and Car-Parrinello molecular dynamics (CPMD) simulation studies. The PA molecule can exist in various rotameric forms at room temperature, trans-trans [TT], trans-gauche [(TG(+))/(TG(-))], gauche-trans [(G(+)T)/(G(-)T)], and gauche-gauche [(G(+)G(-))/(G(-)G(+))], depending upon the rotation about the O3-C4 and C4-C5 bonds of the molecule. The vibrational signatures of different rotameric forms of the PA molecule have been assigned for the first time. Raman and temperature-dependent FTIR spectra of the PA molecule envisage the coexistence of the TT, TG(+)/TG(-), G(+)T/G(-)T, and G(+)G(-)/G( )G(+) forms of the PA molecule at room temperature. However, at low (ca. -95 degrees C) and high temperatures (ca. 65 degrees C), the TG(+) form of the PA molecule is estimated to be preponderant. These results are substantiated by the CPMD simulations, together with the estimation of fwhm values of the vibrational signatures of the PA molecule recorded at high-, room-, and low-temperature domains. PMID- 26145706 TI - Toward Accumulation of Magnetic Nanoparticles into Tissues of Small Porosity. AB - Magnetic concentration of drug-laden magnetic nanoparticles has been proven to increase the delivery efficiency of treatment by 2-fold. In these techniques, particles are concentrated by the presence of a magnetic source that delivers a very high magnetic field and a strong magnetic field gradient. We have found that such magnetic conditions cause even 150 nm particles to aggregate significantly into assemblies that exceed several micrometers in length within minutes. Such assembly sizes exceed the effective intercellular pore size of tumor tissues preventing these drug-laden magnetic nanoparticles from reaching their target sites. We demonstrate that by using dynamic magnetic fields instead, we can break up these magnetic nanoparticles while simultaneously concentrating them at target sites. The dynamic fields we investigate involve precessing the field direction while maintaining a field gradient. Manipulating the field direction drives the particles into attractive and repulsive configurations that can be tuned to assemble or disassemble these particle clusters. Here, we develop a simple analytic model to describe the kinetic thresholds of disassembly and we compare both experimental and numerical results of magnetic particle suspensions subjected to dynamic fields. Finally we apply these methods to demonstrate penetration in a porous scaffold with a similar pore size to that expected of a tumor tissue. PMID- 26145707 TI - Diverse packaging of TF into platelets. PMID- 26145709 TI - An ordered mesoporous Ag superstructure synthesized via a template strategy for surface-enhanced Raman spectroscopy. AB - Surface-enhanced Raman scattering (SERS) substrates with high density and uniformity of nanogaps are proven to enhance the reproducibility and sensitivity of the Raman signal. Up to now, the syntheses of a highly ordered gold or silver superstructure with a controllable nanoparticle size and a well-defined particle gap have been quite limited. Here, we reported an ordered mesoporous silver superstructure replicated by using ordered mesoporous KIT-6 and SAB-15 as templates. By means of a nanocasting process, the ordered mesoporous Ag superstructure was successfully synthesized, which shows uniform distribution of the nanowire diameter (10 nm) and nanogap size (~2 nm), thus exhibiting a high Raman enhancement of ~10(9). The finite difference time-domain (FDTD) results indicate that the ordered mesoporous Ag superstructure has a uniform distribution of hot spots. Therefore, the mesoporous silica template strategy presented here could lead to a new class of high quality SERS substrates providing extraordinary potential for diverse applications. PMID- 26145710 TI - Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi. AB - Rheum emodi is used as a culinary plant across the world and finds an eminent role in the Ayurvedic and traditional Chinese systems of medicine. The plant is known to principally contain 1,8-dihydroxyanthraquinones (DHAQs) like rhein, aloe emodin, emodin, chrysophanol and physcion that possess diverse pharmacological and therapeutic actions. The present work deals with developing a platform technology for isolation of these DHAQs and evaluating their anti-diabetic potential. Herein, we report the anti-hyperglycemic activity and alpha glucosidase (AG) inhibitory actions of five isolated DHAQs from R. emodi. All the five isolated DHAQs showed good anti-hyperglycemic activity with aloe emodin exhibiting maximum lowering of blood glucose in an oral glucose tolerance test. However, on evaluation of the AG inhibitory potential of the DHAQs only emodin exhibited potent intestinal AG inhibition (93 +/- 2.16%) with an IC50 notably lower than acarbose. Subsequent kinetic studies indicated a mixed type of inhibition for emodin. In vivo studies using oral maltose load showed almost total inhibition for emodin when compared to acarbose. Molecular docking studies revealed the presence of an allosteric topographically distinct 'quinone binding site' and showed that interaction with Ser 74 occurs exclusively with emodin, which is vital for AG inhibition. The net benefit from the glucose lowering effect and mixed type inhibition by emodin would enable the administration of a small dosage that is safe and non-toxic in the case of prolonged use in treating diabetes. PMID- 26145711 TI - A chromium nitride/carbon nitride containing graphitic carbon nanocapsule hybrid as a Pt-free electrocatalyst for oxygen reduction. AB - Chromium nitride nanoparticles supported on graphitic carbon nanocapsules containing carbon nitride (CrN/GC) have been synthesized by a solvothermal assisted ion-exchange route. As a Pt-free catalyst, the CrN/GC hybrid exhibits superior activity, stability, methanol immunity and a dominant 4-electron pathway towards oxygen reduction reaction. PMID- 26145712 TI - Homochiral Porous Organic Cage with High Selectivity for the Separation of Racemates in Gas Chromatography. AB - Porous organic molecular cages as a new type of porous materials have attracted a tremendous attention for their potential applications in recent years. Here we report the use of a homochiral porous organic cage (POC) (CC3-R) diluted with a polysiloxane (OV-1701) as a stationary phase for high-resolution gas chromatography (GC) with excellent enantioselectivity. A large number of optical isomers have been resolved without derivatization, including chiral alcohols, diols, amines, alcohol amines, esters, ketones, ethers, halohydrocarbons, organic acids, amino acid methyl esters, and sulfoxides. Compared with commercial beta DEX 120 and Chirasil-L-Val columns, the CC3-R coated capillary column offered more preeminent enantioselectivity. In addition, CC3-R also exhibits good selectivity for the separation of isomers, linear alkanes, alcohols, and aromatic hydrocarbons. The excellent resolution ability, repeatability, and thermal stability make CC3-R a promising candidate as a novel stationary phase for GC. The study described herein first proves useful commercially. This work also indicates that porous organic molecular materials will become more attractive in separation science. PMID- 26145713 TI - Food specific oral immunotherapy: a potential treatment for food allergy. AB - Food allergy is a potentially life-threatening condition affecting up to 8% of children and up to 2% of adults in westernized countries. There are currently no approved treatments for food allergy apart from avoidance. The apparent increase in incidence of food allergies over the past few decades calls attention to the need for effective, disease-modifying therapies for food allergies. Oral immunotherapy (OIT) is a promising experimental treatment in which food allergic patients consume increasing quantities of food in attempt to increase their threshold for allergic reaction. Studies are ongoing to determine whether OIT is capable of safely inducing not only desensitization but also tolerance to the allergenic foods. This article focuses on recent relevant studies of OIT for the treatment of common food allergies. PMID- 26145714 TI - Monitoring performance of progression assessment criteria for cancer antigen 125 among patients with ovarian cancer compared by computer simulation. AB - BACKGROUND: Cancer antigen 125 (CA125) is used to monitor tumor burden among patients with advanced serous epithelial ovarian cancer. The purpose is to compare the monitoring performance of seven previously proposed criteria. MATERIALS & METHODS: The CA125 assessment criteria were applied to simulated datasets. We investigated the ability to provide information on CA125 increments as well as their robustness against false positive signals. RESULTS: For baseline concentrations above cut-off, the best performing criterion was based on a confirmed increment >=2.5-times the nadir concentration. For baseline concentrations below cut-off, the best performing criterion was based on a confirmed increment from <= cut-off to >two-times cut-off. DISCUSSION: Computer simulation models may be useful for a preclinical validation of criteria to be investigated in clinical trials. PMID- 26145715 TI - A plasmon-driven selective surface catalytic reaction revealed by surface enhanced Raman scattering in an electrochemical environment. AB - Plasmonic catalytic reactions of molecules with single amine or nitro groups have been investigated in recent years. However, plasmonic catalysis of molecules with multiple amine and/or nitro groups is still unknown. In this paper, plasmon driven catalytic reactions of 4,4'-dinitroazobenzene (DNAB), 4,4' diaminoazobenzene (DAAB) and 4-nitro-4'-aminoazobenzene (NAAB) are investigated using electrochemical surface-enhanced Raman scattering (SERS) spectroscopy. The results reveal that a plasmon-driven reduction reaction occurred for DNAB and NAAB in which the NO2 group was reduced to NH2, while the plasmon-driven oxidation reaction of NH2 did not occur. This result demonstrates that plasmon driven reduction reactions are much easier than plasmon-driven oxidization reactions in electrochemical environments. The molecular resonance may also play an important role in plasmon-driven catalytic reactions. These findings provide us with a deeper understanding of plasmon-driven catalytic reactions. PMID- 26145716 TI - Creation and manipulation of topological states in chiral nematic microspheres. AB - Topology is a universal concept that is encountered in daily life and is known to determine many static and dynamical properties of matter. Taming and controlling the topology of materials therefore constitutes a contemporary interdisciplinary challenge. Building on the controllable spatial properties of soft matter appears as a relevant strategy to address the challenge, in particular, because it may lead to paradigmatic model systems that allow checking theories experimentally. Here we report experimentally on a wealth of complex free-standing metastable topological architectures at the micron scale, in frustrated chiral nematic droplets. These results support recent works predicting the formation of free standing knotted and linked disclination structures in confined chiral nematic fluids. We also demonstrate that various kinds of external fields (thermal, electrical and optical) can be used to achieve topological remote control. All this may foster the development of new devices based on topologically structured soft media. PMID- 26145717 TI - Being diagnosed with a sexually transmitted infection (STI): sources of support for young women. AB - BACKGROUND: Sexually transmitted infections (STIs) are prevalent throughout the world with the rate of these infections increasing on a daily basis. STI acquisition has the ability to cause personal adversity and elicit feelings of stigma and shame. AIM: The aim of this paper is to report on the sources of support young women who acquired STIs drew on to overcome their associated adversity. METHODS: This study utilised a feminist qualitative methodology. FINDINGS: Findings revealed that the women drew on both personal and anonymous sources of support. CONCLUSION: Nurses and other health-care professionals need to be equipped with knowledge and strategies to promote personal wellbeing and minimise the adversity felt among people having acquired these infections. PMID- 26145718 TI - Validation of Placebo in a Manual Therapy Randomized Controlled Trial. AB - At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment ("yes" or "no") and how strongly they believed that active treatment was received (numeric rating scale 0-10). The outcome measures included the rate of successful blinding and the certitude of the participants' beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months. PMID- 26145719 TI - A straightforward entry to chiral carbocyclic nucleoside analogues via the enantioselective [3+2] cycloaddition of alpha-nucleobase substituted acrylates. AB - A straightforward entry to chiral carbocyclic nucleoside analogues has been realized via the enantioselective [3+2] cycloaddition of alpha-nucleobase substituted acrylates to vinyl cyclopropanes for the first time. With Pd2(dba)3 L5 as the catalyst, carbocyclic purine, uracil, and thymine nucleoside analogues with quaternary stereocenters were obtained in excellent yields (up to 99% yield) and good enantioselectivities (up to 92% ee). PMID- 26145720 TI - Coffinite, USiO4, Is Abundant in Nature: So Why Is It So Difficult To Synthesize? AB - Coffinite, USiO4, is the second most abundant U(4+) mineral on Earth, and its formation by the alteration of the UO2 in spent nuclear fuel in a geologic repository may control the release of radionuclides to the environment. Despite its abundance in nature, the synthesis and characterization of coffinite have eluded researchers for decades. On the basis of the recent synthesis of USiO4, we can now define the experimental conditions under which coffinite is most efficiently formed. Optimal formation conditions are defined for four parameters: pH, T, heating time, and U/Si molar ratio. The adjustment of pH between 10 and 12 leads probably to the formation of a uranium(IV) hydroxo-silicate complex that acts as a precursor of uranium(IV) silicate colloids and then of coffinite. Moreover, in this pH range, the largest yield of coffinite formation (as compared with those of the two competing byproduct phases, nanometer-scale UO2 and amorphous SiO2) is obtained for 250 degrees C, 7 days, and 100% excess silica. PMID- 26145722 TI - Is overprotection of the sulfur cathode good for Li-S batteries? AB - How to restrain the dissolution of polysulfides from the sulfur cathode is the current research focus of Li-S batteries. Here, we find that moderate dissolution of polysulfides is of great importance for high-efficiency and stable discharge/charge cycling. Both overprotection and inadequate protection of the sulfur cathode are unfavorable for the cycling of Li-S batteries. PMID- 26145723 TI - Characterization of Inflammatory Changes Associated with Canine Oligodendroglioma. AB - Oligodendroglioma is a common glial tumour in the dog. In human neuropathology, the immune cell microenvironment of gliomas has been investigated; however, the nature of the inflammatory cells within canine gliomas is currently unknown. The aim of this study was to determine the nature of the immune cells and determine an association between the inflammatory cells and tumour grade. Thirty-four (18 of grade II and 16 of grade III) formalin-fixed and paraffin wax-embedded samples of canine oligodendroglioma were evaluated by light microscopy and immunohistochemistry for expression of CD3, PAX5, Iba-1, HLA-DR, Mac387 and CD31. Variations in immune cell recruitment and activation were evident in all cases. Infiltrating CD3(+) T lymphocytes were common in most cases. PAX5(+) B lymphocytes were less common and restricted to perivascular cuffs within or around the tumour. Iba-1(+) cells were common within the tumour and formed a dense infiltrate around the tumour in a subset of cases. HLA-DR(+) cells were common within the tumour and in a subset of cases formed perivascular cuffs. Iba 1(+) cells typically had prominent ramified processes suggestive of activated microglia, while the HLA-DR(+) cells had a more rounded morphology typical of amoeboid microglia. Rare Mac387(+) macrophages were found in the tumour parenchyma, while increased numbers of Mac387(+) monocytes were noted within the vasculature. No association or significance was established between the immune cell infiltrate and the grade of the tumour (all P >=0.16). This study establishes that there is a robust population of immune cells within canine oligodendrogliomas and indicates that further study is needed to determine the role of these cells in tumour pathogenesis and progression. PMID- 26145721 TI - Osseointegrated total knee replacement connected to a lower limb prosthesis: 4 cases. AB - BACKGROUND AND PURPOSE: Osseointegrated implants are an alternative for prosthetic attachment in individuals with amputation who are unable to wear a socket. However, the load transmitted through the osseointegrated fixation to the residual tibia and knee joint can be unbearable for those with transtibial amputation and knee arthritis. We report on the feasibility of combining total knee replacement (TKR) with an osseointegrated implant for prosthetic attachment. PATIENTS AND METHODS: We retrospectively reviewed all 4 cases (aged 38-77 years) of transtibial amputations managed with osseointegration and TKR in 2012-2014. The below-the-knee prosthesis was connected to the tibial base plate of a TKR, enabling the tibial residuum and knee joint to act as weight-sharing structures. A 2-stage procedure involved connecting a standard hinged TKR to custom-made implants and creation of a skin-implant interface. Clinical outcomes were assessed at baseline and after 1-3 years of follow-up using standard measures of health-related quality of life, ambulation, and activity level including the questionnaire for transfemoral amputees (Q-TFA) and the 6-minute walk test. RESULTS: There were no major complications, and there was 1 case of superficial infection. All patients showed improved clinical outcomes, with a Q-TFA improvement range of 29-52 and a 6-minute walk test improvement range of 37-84 meters. INTERPRETATION: It is possible to combine TKR with osseointegrated implants. PMID- 26145724 TI - Analysis of Hypoxia-Inducible Factor-1alpha Expression Relative to Other Key Factors in Malignant Canine Mammary Tumours. AB - Hypoxia-inducible factor (HIF)-1alpha plays important physiological roles, but is also of significance in carcinogenesis in man and animals. This study aimed to identify HIF-1alpha expression in malignant canine mammary tumours (CMTs) and to find correlations with other key factors by using immunohistochemistry (IHC). The histological classification, grading and evaluation of lymphatic invasion were achieved by examining sections stained by haematoxylin and eosin. Determination of molecular subtype, expression of HIF-1alpha, oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor (HER)-2, Ki67, vascular endothelial growth factor (VEGF) and E-cadherin was evaluated by IHC in 87 samples of malignant CMTs. HIF-1alpha expression correlated significantly with histological type, grade of cancer, negativity for OR and expression of Ki67 and VEGF. Lymphatic invasion, molecular subtype, PR, HER-2 and E-cadherin levels did not significantly correlate with HIF-1alpha expression. The results of this study imply that HIF-1alpha may potentially play a role in increased malignancy of CMTs, as it does in human breast cancer. PMID- 26145725 TI - "Re: The Benefit of Revascularization in Nonagenarians With Lower Limb Ischemia is Limited by High Mortality". PMID- 26145726 TI - [Peritoneal tumor pathology: introduction]. PMID- 26145727 TI - Porphyrin-based graphene oxide frameworks with ultra-large d-spacings for the electrocatalyzation of oxygen reduction reaction. AB - Graphene oxide frameworks (GOFs) have attracted a great deal of attention because of their unique functional building blocks, and tunable structures and properties. Herein, a series of porphyrin-based GOFs with crystalline lamellar structures were synthesized via esterification between boronic acid groups of porphyrins and hydroxyl groups of GO sheets. These GOFs have ultra-large d spacings of up to 26.0 A, and they were reduced by facile electrochemical reduction. The resulting reduced GOFs (rGOFs) can be used as catalysts for oxygen reduction reaction (ORR). Electrochemical reduction improved the conductivities of GOFs, accelerating the charge transfer of ORR. The rGOF with Co-porphyrin showed the most positive onset potential of ORR at 0.89 V (vs. RHE, reversible hydrogen electrode), while the rGOF with Fe-porphyrin exhibited the highest catalytic efficiency through an approximately four-electron process. This study provides a new insight for the development of GOFs using multi-functional macrocyclic molecules, revealing their promising applications in electrocatalysts. PMID- 26145729 TI - Synthesis and Nematicidal Activities of 1,2,3-Benzotriazin-4-one Derivatives against Meloidogyne incognita. AB - A series of novel 1,2,3-benzotriazin-4-one derivatives were synthesized by the reaction of 3-bromoalkyl-1,2,3-benzotriazin-4-ones with potassium salt of 2 cyanoimino-4-oxothiazolidine in the presence of potassium iodide. Nematicidal assays in vivo showed that some of them exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita, up to 100% at the concentration of 10.0 mg L(-1), which indicated that 1,2,3 benzotriazin-4-one derivatives might be potential for novel promising nematicides. The nematicidal activity was influenced by the combination of substituent type, substituted position, and linker length in the molecule. The inhibition rate data at the concentrations of 5.0 and 1.0 mg L(-1) for the compounds with high inhibitory activities were also provided. When tested in vitro, none of them showed direct inhibition against M. incognita. The investigation of a significant difference between in vivo and in vitro data is in progress. PMID- 26145730 TI - Shared and Divergent Auditory and Tactile Processing in Children with Autism and Children with Sensory Processing Dysfunction Relative to Typically Developing Peers. AB - The aim of this study was to compare sensory processing in typically developing children (TDC), children with Autism Spectrum Disorder (ASD), and those with sensory processing dysfunction (SPD) in the absence of an ASD. Performance-based measures of auditory and tactile processing were compared between male children ages 8-12 years assigned to an ASD (N=20), SPD (N=15), or TDC group (N=19). Both the SPD and ASD groups were impaired relative to the TDC group on a performance based measure of tactile processing (right-handed graphesthesia). In contrast, only the ASD group showed significant impairment on an auditory processing index assessing dichotic listening, temporal patterning, and auditory discrimination. Furthermore, this impaired auditory processing was associated with parent-rated communication skills for both the ASD group and the combined study sample. No significant group differences were detected on measures of left-handed graphesthesia, tactile sensitivity, or form discrimination; however, more participants in the SPD group demonstrated a higher tactile detection threshold (60%) compared to the TDC (26.7%) and ASD groups (35%). This study provides support for use of performance-based measures in the assessment of children with ASD and SPD and highlights the need to better understand how sensory processing affects the higher order cognitive abilities associated with ASD, such as verbal and non-verbal communication, regardless of diagnostic classification. PMID- 26145728 TI - Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection. AB - We reported previously that priming of the respiratory tract with immunobiotic Lactobacillus prior to virus challenge protects mice against subsequent lethal infection with pneumonia virus of mice (PVM). We present here the results of gene microarray which document differential expression of proinflammatory mediators in response to PVM infection alone and those suppressed in response to Lactobacillus plantarum. We also demonstrate for the first time that intranasal inoculation with live or heat-inactivated L. plantarum or Lactobacillus reuteri promotes full survival from PVM infection when administered within 24h after virus challenge. Survival in response to L. plantarum administered after virus challenge is associated with suppression of proinflammatory cytokines, limited virus recovery, and diminished neutrophil recruitment to lung tissue and airways. Utilizing this post-virus challenge protocol, we found that protective responses elicited by L. plantarum at the respiratory tract were distinct from those at the gastrointestinal mucosa, as mice devoid of the anti-inflammatory cytokine, interleukin (IL)-10, exhibit survival and inflammatory responses that are indistinguishable from those of their wild-type counterparts. Finally, although L. plantarum interacts specifically with pattern recognition receptors TLR2 and NOD2, the respective gene-deleted mice were fully protected against lethal PVM infection by L. plantarum, as are mice devoid of type I interferon receptors. Taken together, L. plantarum is a versatile and flexible agent that is capable of averting the lethal sequelae of severe respiratory infection both prior to and post-virus challenge via complex and potentially redundant mechanisms. PMID- 26145731 TI - [Validation of the Spanish version of the HIV Related Fatigue Scale and application in people with hepatitis C]. AB - OBJECTIVES: To validate the American fatigue scale HIV-Related Fatigue Scale (HRFS) and present the Spanish version called Integrated Fatigue Assessment Scale to assess fatigue in HCV and co-infected patients. METHOD: Psychometric study with cross-sectional design was used. The HRFS was translated into Spanish using the back-translation method-later to be validated. Participants completed the questionnaire adapted to a self-report form, as well as a sociodemographic questionnaire. The reliability and validity of the Spanish version was evaluated. RESULTS: A total of 7 public service hospitals and two prisons in Catalonia participated in the evaluation. The sample consisted of 122 subjects selected by consecutive sampling in the fourth week of treatment of hepatitis C with combination therapy or triple therapy. The Cronbach alpha for the total scale was 0.958. Content Validity Index (I-CVI) varied from 0.5 to 1. Validity Scale Content-level (S-CVI) was 0.85. Pearson correlations between the three dimensions were between 0.49 and 0.68. CONCLUSIONS: The process followed for the cultural adaptation and validation shows that the Spanish version of the HRFS) is a valid and reliable instrument that can be used in clinical practice and in the investigation of fatigue in patients with hepatitis C. PMID- 26145733 TI - Viral evolution: Keeping a watchful eye on Ebola. PMID- 26145734 TI - Access to mental health services and psychotropic drug use in refugees and asylum seekers hosted in high-income countries. AB - In the populations of refugees and asylum seekers hosted in high-income countries, access to mental health care and psychotropic drugs, is a major challenge. A recent Swedish cross-sectional register study has explored this phenomenon in a national cohort of 43 403 young refugees and their families from Iraq, Iran, Eritrea, Ethiopia, Somalia and Afghanistan. This register study found lower rates of dispensed psychotropic drugs among recently settled refugees, as compared with Swedish-born residents, with an increase in the use with duration of residence. In this commentary, the results of this survey are discussed in view of their global policy implications for high-income countries hosting populations of refugees and asylum seekers. PMID- 26145732 TI - A functional perspective on phenotypic heterogeneity in microorganisms. AB - Most microbial communities consist of a genetically diverse assembly of different organisms, and the level of genetic diversity plays an important part in community properties and functions. However, biological diversity also arises at a lower level of biological organization, between genetically identical cells that reside in the same microenvironment. In this Review, I outline the molecular mechanisms responsible for phenotypic heterogeneity and discuss how phenotypic heterogeneity allows genotypes to persist in fluctuating environments. I also describe how it promotes interactions between phenotypic subpopulations in clonal groups, providing microbial groups with new functionality. PMID- 26145736 TI - [The diagnostic significance of the clinical methods for the investigation into the oculomotor reactions to dizziness]. AB - The objective of the present study was to estimate the diagnostic significance of the physical vestibular tests designed to investigate the oculomotor reactions in order to determine the severity of disturbances in the vestibular analyzer during the primary examination of the patients presenting with dizziness symptoms. The results of the study suggest the desirability of using the Frenzel goggles for the detection of the presence of latent spontaneous nystagmus and the performance of additional testing. The study of the vestibular-ocular reflex should begin from the head turn test to be supplemented, in the case of the dubious result, by the dynamic visual acuity test. The smooth pursuit test, the visual saccade test, and the optic nystagmus test need to be performed on a full scale. The subjective visual vertical test should be carried out at the later stages of diagnostics when the detailed investigation of the vestibular function is conducted. The positional manoeuvers are the indispensable components of the examination of the patients presenting with pathological changes in the vestibular analyzer by virtue of their high diagnostic significance for the detection of benign paroxysmal positional dizziness. PMID- 26145737 TI - [The application of ultrasound for diagnostics of middle ear pathologies]. AB - The objective of the present work was to summarize the results of the application of ultrasound tests for differential diagnostics of various diseases and lesions affecting the middle ear. Almost 7.000 threshold and suprathreshold studies were carried out in the patients presenting with various forms of sensorineural impairment of hearing. The ultrasound investigations were conducted with the use of the EKHOTEST-02 apparatus (Giperion, Moscow). The results of determination of threshold hearing sensitivity to ultrasound and lateralization of its threshold and suprathreshold values suggest their significance for the detection of even such a minimal disturbance in the cochlear function as the phenomenon of accelerated increase in loudness and the associated enhancement of the severity of the damage to the peripheral sensory system. PMID- 26145738 TI - [The clinical evaluation of the effectiveness of anterior craniofacial resection for the treatmentof disseminated tumours and pseudotumour lesions in the nasal cavity, the paranasal sinuses, and the orbit]. AB - The objective of the present work was to evaluate the outcomes of anterior craniofacial resection (ACFR) in the patients presenting with disseminated tumours and pseudotumour lesions in the nasal cavity, the paranasal sinuses, and the orbit based on the results of dynamic clinical observations. A total of 24 patients with tumours and tumour-like lesions of these anatomical structures were involved in the study including 14 ones having benign neoplasms, 2 patients with pseudotumour lesion, and 8 patients having malignant tumours. In all the cases, the pathological processes in the form of destruction and infiltration encompassed the anterior portion of the base of the skull (mostly lamina cribrosae) and spread directly into the anterior cranial fossa. It was shown that ACRF ensured the radical elimination of the pathological process and the enhancement of the five-year survival rate in all the patients with benign tumours and pseudotumour lesions and in half of the patients presenting with disseminated malignant neoplasms. PMID- 26145739 TI - [The results of a comparative randomized study of the effectiveness of various methods for the correction of the nasal valve: the objective evaluation]. AB - The present comparative randomized controlled study was designed to evaluate the effectiveness of the most widely used methods for the surgical treatment of nasal valve dysfunction including sutural extension of the valve, stretching the lateral nasal wall in combination with the application of strengthening transplants, and the introduction of tissue expanders. The objective studies were carried out with the use of anterior active rhinomanometry and acoustic rhinometry performed within 1, 3, and 12 months after surgery. It was shown that the correction of dysfunction of the nasal valve with the application of expanding transplants is the most effective method for the normalization of the parameters of nasal breathing during the mid- and long-term follow up. Plastic surgery with the use of local tissues produces a less pronounced but stable beneficial effect whereas the sutural extension of the valve yields only short term positive results. On the whole, the effectiveness of the latter approach is inferior to that of the former two methods. PMID- 26145740 TI - [The character of variations in the relationships of lymphocyte subpopulations in the patients presenting with chronic decompensated tonsillitis]. AB - The palatine tonsils are known to be involved in the formation of cellular and humoral immunity. Apoptosis is believed to be one of the main biological mechanism regulating the quantitative composition of subpopulations of the immunocompetent cells. Therefore, the prevalence of apoptotic and anti-apoptotic processes determines the direction of the immune response. Bearing this in mind, we have undertaken a study with a view to elucidating the relationships between lymphocyte subpopulations in the blood and homogenates of the palatal tonsils in the patients with chronic decompensated tonsillitis and establishing their interdependence with the levels of apoptosis and necrosis. The quantification of apoptosis and necrosis as well as the ratio of these processes in neutrophils and lymphocytes belonging to different subpopulations of palatal tonsil homogenates and peripheral blood was performed by cytofluorometry with the use of the "BecmenCulter Epi XL" apparatus (USA). It has been found that decompensated chronic tonsillitis is associated with the depression of cellular immunity apparent as the 2 or 3-fold reduction of lymphocyte CD3, CD4m and CD8 subsets (as compared with the respective normal levels). The number of CD16 and CD19 lymphocytes remains unaltered witch suggests that humoral immunity is un affectred. It is concluded that the apoptosis-necrosis index and the relationship between different subpopulations of lymphocytes in the peripheral blood may be the additional indicator to be used for diagnostics of decompensated forms of chronic tonsillitis. PMID- 26145741 TI - [The algorithm for the combined treatment of pyoinflammatory ENT diseases in the patients with diabetes mellitus]. AB - The objective of the present study was to determine the leading clinical and pathogenetic factors determining the clinical course of the pyoinflammatory ENT diseases in the patients with diabetes mellitus (DM) and to develop the algorithm for the rational therapy of these conditions. A total of 145 patients presenting with pyoinflammatory ENT diseases and concomitant diabetes mellitus were available for the examination that included the microbiological and biochemical studies, determination of the total lipid spectrum, glycated hemoglobin (HbA1c) level, and glycemic profile. Also, the body mass index of the patients was estimated along with the type and severity of obesity. Moreover, the character of antibacterial and hypoglycemic therapy was evaluated. The mathematical analysis of the data obtained revealed the clinical and biochemical parameters determining the clinical picture of the pyoinflammatory ENT diseases in the patients with diabetes mellitus. These were localization of the pyogenic process in the larynx, abdominal obesity, fasting hyperglycemia in excess of 8.3 mmol/l, and dyslipidemia accompanied by the reduction in the amount of high density lipoproteins to below 40 mg/100 ml and the increase of low density lipoproteins to above 155 mg/100 ml. The results of the study were used to develop the differentialalgorithm for the combined treatment of pyoinflammatory ENT diseases in the patients with diabetes mellitus based on the proposed original scale for the prediction of pyogenic complications. PMID- 26145743 TI - [The method for the direct evaluation of the state of mucociliary clearance in the children]. AB - The objective of the present study was to develop a readily available, simple to use and acceptable for the application in the childhood method for the evaluation of the state of mucociliary clearance. We have proposed and presented the detailed description of the simple approach to the direct investigation of the ciliary apparatus of the ciliary epithelium cells that requires neither the expensive sophisticated equipment nor the software programs to be implemented. Investigations by this method made it possible to elucidate and identify certain details of the functioning of ciliary epithelium. Other methods for the study of the ciliary apparatus are considered with special reference to their main advantages and disadvantages. Some debatable problems pertaining to the choice of optimal techniques for the evaluation of the functional state of ciliary epithelium are discussed. PMID- 26145742 TI - [The disturbances of vegetative homeostasis in the children suffering from vasomotor rhinitis]. AB - The objective of the present work was to study the state of the vegetative homeostasis in 157 children presenting with vasomotor rhinitis. It was shown that the children with this pathology suffer from vegetative dysfunction. The forms of this disorder are various which require the mulidisciplinary approach to their diagnostics and treatment. PMID- 26145744 TI - [The mechanical properties of the bone tissue from the middle facial region]. AB - The objective of the present work was to study age-related features of the reaction of the maxillary sinus cavity walls to a variety of impacts associated with the surgical interventions. To this effect, a variety of stress-strain conditions were simulated that are known to arise in the maxillary sinus cavity walls under the action of different force vectors taking into consideration the age-specific peculiarities of the mechanical structure of the bone tissue. The 3D model of the maxillary sinus cavity was built up based on the results of spiral computed tomography with the use of the Solid Works 2012 software package (USA). The finite element method (FEM) was employed to construct the grid. Three variants of force application were simulated, one to the canine fossa region, another to the upper portion of the alveolar process at the border between the upper and lower walls of the sinus, and the third to the anterior part of the inferior nasal passage. The study has demonstrated that the bone wall of the maxillary sinus differently responds to the impacts of similar magnitude depending on the application point and age-related physical and mechanical properties of the bone tissue. This finding should be taken into account in the choice of the optimal surgical approach to the maxillary sinus. It was calculated that endonasal interventions should be preferred for the treatment of patients above 60 years of age as the minimally injurious ones to the bone tissue. Moreover, special caution is needed when the intervention is performed beneath the canine fossa, where the bone is extremely fragile and the risk of injury extension to the floor of the maxillary sinus is especially high. PMID- 26145745 TI - [The prevalence and structure of ENT diseases in the children residing in the industrial regions]. AB - The present study was designed to evaluate the state of the ENT organs in the children residing in the industrial regions characterized by the enhanced level of atmospheric pollution. The results of the correlation analysis of the data obtained confirm the strong cause-and-effect relationship between the pathologies of the upper respiratory tract (such as allergic and catarrhal rhinitis, chronic pharyngitis, sinusitis, inflammatory tonsillar diseases, and adenoid vegetations), impaired local immune reactivity, and the index of general air pollution including that with nitrous dioxide, phenols, and particulate matter. The results of the study suggest the necessity of more active detection of ENT diseases in the children at the early stages of their development together with regular medical examinations, and the implementation of purpose-oriented prophylactic, therapeutic, and health promoting measures. PMID- 26145746 TI - [The experience with the use of the two-step laryngotracheoplasty for the management of subglottic and combined subglottic and upper tracheal cicatrical stenosis in the adult patients]. AB - The objective of the present retrospective study was to evaluate the clinical experience with the use of the two-step laryngotracheoplasty for the treatment of subglottic and combined subglottic and upper tracheal cicatrical stenosis in the adult patients during the period between 2003 and 2012. A total of 13 patients were retrospectively reviewed following the surgical treatment for the management of subglottic and combined subglottic and upper tracheal cicatrical stenosis based at the Lugansk regional clinical hospital. The effectiveness of two-stage laryngotracheoplasty was estimated to be 84.6%. The number of the surgical procedures per patient depended on the extent of tracheal stenosis while the overall rehabilitation period mainly depended on the severity of the concomitant pathologies. The technical aspects and the results of the surgical treatment are discussed. PMID- 26145747 TI - [The early prophylaxis of postoperative stenosis by means of modifiedendonasal functional dacryocystorhinostomy]. AB - The objective of the present study was to increase the effectiveness of the prevention of the postoperative complications by means of the newly proposed modified variant of endonasal functional dacryocystorhinostomy. The method was used to treat 230 patients presenting with chronic dacryocystitis. It was shown that the new method permits to prevent the recurrence of the pathological process by virtue of the attachment of the middle nasal turbinates to the nasal septum and the prevention of its adhesion to the dacryostoma. The prevention of fibrin precipitation near the operative field is possible thanks to the ointment discharge through the perforations towards the cavity of the newly for meddacryostoma . Simultaneously, the formation of the organized blood clots is prevented. At a later stage, the silicone plate introduced to adjoin the middle nasal turbinate becomes an obstacle to the formation of adhesions. It is concluded that the proposed functional arrangement of the nasal structures and the outflow of tears makes it possible to reduce the recurrence of the disease to 2.1% of the cases. PMID- 26145748 TI - [The modern approach to the treatment of the patients presenting with vasomotor rhinitis with the use of the electrosurgical technique]. AB - The objective of the present study was to compare, based on the clinical data, the effectiveness of the electrosurgical techniques of the molecular resonance and radio-wave ranges used to perform vasotomy in 64 patients presenting with vasomotor rhinitis. The short-term results of the treatment suggest the higher effectiveness and safety of radio-wave surgery in comparison with the molecular resonance treatment in the patients with the above condition. This observation was confirmed in the objective studies with the use of endoscopic and cytological methods, anterior active rhinomanometry, and determination of mucociliary clearance. PMID- 26145749 TI - [The possibility of using tranexamic acid for the treatment of bleeding in otorhinolaryngology]. AB - This article is focused on the analysis of the literature publications pertaining to the problem of bleeding in otorhinolaryngology. It reports the epidemiological data on the structure of bleeding and the main methods used to arrest it. Special attention is given to the possibilities of application of tranexamic acid as an effective hemostatic agent not only for systemic but also for topical administration. PMID- 26145750 TI - [Extended laryngotracheal stenosis and osteochondroplastic tracheopathy]. AB - The present article was designed to report a case of the surgical treatment of the patient presenting with extended laryngotrachealstenosis related toosteochondroplasticlaryngo- and tracheopathy. The development of the osteochondroplastic transformation of the laryngeal and tracheal walls was regarded as a single pathomorphologicalprocess associated with chronic inflammation. The study has demonstrated the relationship between the squamous cell hyperplasia in the epithelium of the upper respiratory tract and destructive chondro-perichondritis of the larynx and trachea accompanied by osteochondroplastic changes and concomitant extended laryngotracheal stenosis. PMID- 26145751 TI - [The successful treatment of the combined penetrating gunshot wound of the orbit, ethmoidal labyrinth cells, and sphenoidal sinus containing a foreign body]. PMID- 26145752 TI - Whether or not to eat: A controlled laboratory study of discriminative cueing effects on food intake in humans. AB - There is a wealth of data showing a large impact of food cues on human ingestion, yet most studies use pictures of food where the precise nature of the associations between the cue and food is unclear. To test whether novel cues which were associated with the opportunity of winning access to food images could also impact ingestion, 63 participants participated in a game in which novel visual cues signalled whether responding on a keyboard would win (a picture of) chocolate, crisps, or nothing. Thirty minutes later, participants were given an ad libitum snack-intake test during which the chocolate-paired cue, the crisp paired cue, the non-winning cue and no cue were presented as labels on the food containers. The presence of these cues significantly altered overall intake of the snack foods; participants presented with food labelled with the cue that had been associated with winning chocolate ate significantly more than participants who had been given the same products labelled with the cue associated with winning nothing, and in the presence of the cue signalling the absence of food reward participants tended to eat less than all other conditions. Surprisingly, cue-dependent changes in food consumption were unaffected by participants' level of contingency awareness. These results suggest that visual cues that have been pre-associated with winning, but not consuming, a liked food reward modify food intake consistent with current ideas that the abundance of food associated cues may be one factor underlying the 'obesogenic environment'. PMID- 26145753 TI - Risk Factors for 30-Day Hospital Readmission in Patients Undergoing Treatment for Peripheral Artery Disease. AB - Early hospital readmission among vascular surgery patients is a focus of Medicare's new reimbursement structure. We aim to identify factors associated with 30-day readmission after lower extremity interventions to treat peripheral artery disease (PAD). Retrospective analysis of 174 consecutive patients discharged from the vascular surgery service between January 1, 2011, and July 31, 2012, after procedures for lower extremity PAD was performed. Of 174 patients, 37 were readmitted within 30 days of discharge. There were no significant differences in baseline characteristics between the readmitted and the nonreadmitted groups. In a multivariate logistic regression model, urgent operation and advanced chronic kidney disease (CKD) were associated with increased risk of 30-day readmission. The most common reasons for readmission were infection of the surgical site or index limb (18 of 37), followed by unresolved limb symptoms (13 of 37). The 30-day readmission is frequent after lower extremity interventions to treat PAD. Urgent operative intervention and advanced CKD appear to be risk factors for early hospital readmission. PMID- 26145754 TI - Short-Term Outcomes of Management of Endovascular Aneurysm Repair in Patients With Dilated Iliacs. AB - OBJECTIVES: This study aims to evaluate outcomes following endovascular aneurysm repair (EVAR) in patients with dilated but not aneurysmal common iliac arteries. METHODS: Data prospectively collected from 342 elective EVARs were analyzed retrospectively. Dilated common iliac anatomy was defined as 21 to 24 mm. Patients with iliac aneurysms or external iliac artery (EIA) extension were excluded. Patients were followed up using clinical review, plain radiographs, duplex imaging, and selective computed tomography scanning. RESULTS: Median age was 75 years with a mean follow-up of 3.6 years. In all, 33 patients had dilated common iliac arteries (DCIAs) and 309 had non-dilated common iliac arteries (NDCIA). There was no difference in aneurysm diameter or neck characteristics (length, diameter, angulation, thrombus, and flare) between the subgroups. There was no significant difference in technical success, 30-day mortality, late mortality, aneurysm-related mortality, 30-day reinterventions, stent graft migration, limb occlusion, sac expansion, graft rupture, type 1 endoleaks, type 3 endoleaks, and total reinterventions (all Ps > .05). There was a significant decrease in type II endoleaks in patients with DCIA compared to NDCIA (NDCIA 12.9% and DCIA 0.0%; P = .02). CONCLUSION: Patients presenting with abdominal aortic aneurysms with DCIA can be successfully treated with EVAR with no increase in complications without extension into the EIA. PMID- 26145755 TI - Concentration- and chromosome-organization-dependent regulator unbinding from DNA for transcription regulation in living cells. AB - Binding and unbinding of transcription regulators at operator sites constitute a primary mechanism for gene regulation. While many cellular factors are known to regulate their binding, little is known on how cells can modulate their unbinding for regulation. Using nanometer-precision single-molecule tracking, we study the unbinding kinetics from DNA of two metal-sensing transcription regulators in living Escherichia coli cells. We find that they show unusual concentration dependent unbinding kinetics from chromosomal recognition sites in both their apo and holo forms. Unexpectedly, their unbinding kinetics further varies with the extent of chromosome condensation, and more surprisingly, varies in opposite ways for their apo-repressor versus holo-activator forms. These findings suggest likely broadly relevant mechanisms for facile switching between transcription activation and deactivation in vivo and in coordinating transcription regulation of resistance genes with the cell cycle. PMID- 26145757 TI - Scum sludge as a potential feedstock for biodiesel production from wastewater treatment plants. AB - The main goal of this study was to compare the component and yield of biodiesel obtained by different methods from different sludge in a wastewater treatment plant. Biodiesel was produced by ex-situ and in-situ transesterification of scum, primary and secondary sludge respectively. Results showed that scum sludge had a higher calorific value and neutral lipid than that of primary and secondary sludge. The lipid yield accounted for one-third of the dried scum sludge and the maximum yield attained 22.7% under in-situ transesterification. Furthermore the gas chromatography analysis of fatty acid methyl esters (FAMEs) revealed that all sludge contained a significant amount of palmitic acid (C16:0) and oleic acid (C18:1) regardless of extraction solvents and sludge types used. However, the difference lay in that oleic acid methyl ester was the dominant component in FAMEs produced from scum sludge while palmitic acid methyl ester was the dominant component in FAMEs from primary and secondary sludge. In addition, the percentage of unsaturated fatty acid ester in FAMEs from scum sludge accounted for 57.5 64.1% of the total esters, which was higher than the equivalent derived from primary and secondary sludge. In brief, scum sludge is a potential feedstock for the production of biodiesel and more work is needed in the future. PMID- 26145758 TI - Families' Perceptions of and Experiences Related to a Pediatric Weight Management Intervention: A Qualitative Study. AB - OBJECTIVE: To examine parents' and children's perceptions of and experiences related to a Parents as Agents of Change (PAC) intervention for managing pediatric obesity. METHODS: Ten families were recruited from a PAC intervention. Participants were interviewed before (10 adults and 9 children), during (9 adults and 8 children), and after (8 adults) the intervention. RESULTS: Before the intervention, families reported goals to increase physical activity, plan and eat healthier meals, reduce screen time, and lose weight. During the intervention, families described different approaches to making behavior changes depending on who assumed responsibility (parent, child, or shared responsibility). After the intervention, group setting, goal setting, and portion size activities were viewed positively. Suggestions for improvement included engaging children and reducing intervention length. CONCLUSIONS AND IMPLICATIONS: Practitioners delivering PAC interventions should discuss families' goals and concerns, and who is responsible for making lifestyle changes. Practical activities are valuable. The length of interventions and engagement of children should be considered. PMID- 26145756 TI - Repetitive Transcorneal Alternating Current Stimulation Reduces Brain Idling State After Long-term Vision Loss. AB - BACKGROUND: Deafferentation of visual system structures following brain or optic nerve injury leaves cortical areas deprived of visual input. Deprived cortical areas have a reduced sensory information processing and are characterized with localized enhanced or synchronized rhythms believed to represent an "idling state". OBJECTIVE/HYPOTHESIS: We hypothesized that cortical idling can be modified with transcorneal alternating current stimulation (tACS) known to modulate cortical oscillations and thus change the functional state of the deafferented areas. METHODS: tACS was applied in rat model of severe optic nerve crush using a protocol similar to our clinical studies (200 MUA, 2-8 Hz) for 5 treatment days right after the lesion and at the chronic stage (3 months later). EEG and VEP were recorded over the visual cortices. In vivo confocal neuroimaging of the retina and histology of the optic nerves were performed. RESULTS: Morphological investigations showed massive retinal ganglion cells death and degeneration of the optic nerves after crush. Visual loss was associated with increased EEG spectral power and lower coherence, indicating an "idling state". Stimulation induced a significant decrease of EEG power towards normal values. These effects were especially pronounced in the chronic stage. CONCLUSION: Our results suggest that alternating current injected via the eye is able to modulate visually deprived brain areas and thus reduce cortical idling. PMID- 26145759 TI - Demographic, Physiologic, and Psychosocial Correlates of Physical Activity in Structured Exercise and Sports Among Low-Income, Overweight Children. AB - OBJECTIVE: To describe correlates of physical activity (PA) in structured exercise and structured sports sessions among low-income, overweight children participating in a community-based PA program. METHODS: A total of 93 children (55% male; 91% Hispanic) aged 8-14 years were included. Participants wore pedometers in a sample of 10 of 59 total sessions offered; mean steps per minute were calculated for structured exercise and sports sessions. Separate multivariable regression models tested associations between steps per minute in exercise and sports sessions and 5 potential correlates: baseline body mass index z-score, aerobic fitness (Progressive Aerobic Cardiorespiratory Endurance Run laps), perceived athletic competence (Harter self-perception profile), sex, and age. RESULTS: Only age (beta = -2.9; P = .02) significantly predicted steps per minute in exercise sessions. Age (beta = -4.3; P = .007), fitness (beta = 0.45; P = .03), and male sex (beta = 8.7; P = .02) significantly predicted steps per minute in sports. CONCLUSION AND IMPLICATIONS: In structured exercise and sports, perceived competence may not influence overweight and obese children's PA. However, girls and older or less fit children may engage less actively, especially in sports. PMID- 26145760 TI - Rectal and colon cancer: Not just a different anatomic site. AB - Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs. PMID- 26145761 TI - Re: Single Fraction Radiosurgery for the Treatment of Renal Tumors: M. Staehler, M. Bader, B. Schlenker, J. Casuscelli, A. Karl, A. Roosen, C. G. Stief, A. Bex, B. Wowra and A. Muacevic J Urol 2015; 193: 771-775. PMID- 26145762 TI - Re: Single Fraction Radiosurgery for the Treatment of Renal Tumors: M. Staehler, M. Bader, B. Schlenker, J. Casuscelli, A. Karl, A. Roosen, C. G. Stief, A. Bex, B. Wowra and A. Muacevic J Urol 2015; 193: 771-775. PMID- 26145764 TI - Coadministration of the Human Umbilical Cord Matrix-Derived Mesenchymal Cells and Aspirin Alters Postischemic Brain Injury in Rats. AB - BACKGROUND: Ischemic stroke is an acute brain insult that induces dramatic changes in the neurons. Treatment of brain stroke is one of the main therapeutic targets of neuroprotective therapies. The aim of this study was to evaluate the protective potential of implanted human umbilical cord mesenchymal stem (hUCMs) cells with/without aspirin (ASA) against focal cerebral ischemia. METHODS: We assessed the migration and distribution of PKH26-labeled cells after transplantation. After day 10 of transient occlusion, we evaluated the effect of ASA and hUCMs on the recovery of learning and memory in rats by Morris water maze. Afterward, animals were sacrificed, and the infarct area in the brain was evaluated using 2, 3, 5-triphenyltetrazolium chloride staining and also by hematoxylin and eosin. RESULTS: The recovery of learning and memory in ischemic animals that received ASA and hUCM cells improved significantly compared with the untreated ischemic animals. Coadministration of ASA and hUCM cells did not improve the outcome at a comparable rate with ASA and hUCM cells alone. PKH26 labeled cells were detectable in the ischemic area of the brain tissue sections. 2,3,5-Triphenyltetrazolium chloride staining and histologic examinations showed that treatment with ASA and hUCM cells could significantly alter the ischemic area. CONCLUSIONS: The results of the present study suggest that ASA and hUCM cells can withstand degenerative changes induced by artificial stroke in the rat. Also the learning and memory disturbance in the ASA and cell-treated animals is less pronounced than ischemic animals. Coadministration of ASA and hUCM cells did not raise the outcome higher than administration of ASA and hUCM cells alone. PMID- 26145765 TI - Intraoperative vacuum-assisted closure following in situ graft replacement for an infected thoracic aortic graft. PMID- 26145766 TI - Are devices for temporary mechanical circulatory support getting safer? PMID- 26145767 TI - Surgical management of competing pulmonary blood flow affects survival before Fontan/Kreutzer completion in patients with tricuspid atresia type I. AB - OBJECTIVES: To determine the association between surgical management of pulmonary blood flow (PBF) at initial and staged procedures with survival to Fontan/Kreutzer operation (Fontan) in patients with tricuspid atresia. METHODS: Infants aged <3 months with tricuspid atresia type I (n = 303) were enrolled from 34 institutions (1999-2013). Among those who underwent surgical intervention (n = 302), initial procedures were: systemic to pulmonary artery shunt (SPS; n = 189; 62%); pulmonary artery banding (PAB; n = 50; 17%); and superior cavopulmonary connection (SCPC; n = 63; 21%). Multiphase parametric-hazard models were used to analyze competing outcomes. RESULTS: Risk-adjusted 6-year survival was lower after SPS (85%; P = .04) versus PAB (93%) or SCPC (93%). Survival after SPS when the main pulmonary artery (MPA) was closed (n = 21) or banded (n = 4) was 60%, versus 93% without MPA intervention (P = .02). After SPS, survival before SCPC was lower with an open ductus arteriosus (n = 7; 76% vs 97%; P = .02). Similarly, after SPS, risk-adjusted survival was similar to that for patients who had an initial PAB or SCPC when MPA intervention was avoided and the ductus arteriosus either closed spontaneously before SPS, or was closed during SPS. For all patients reaching SCPC (n = 277), survival to Fontan was not significantly influenced by whether PBF persisted through the MPA. CONCLUSIONS: Tricuspid atresia patients with SPS represent a high-risk subgroup. Avoiding an open ductus arteriosus and concomitant MPA intervention during SPS may help mitigate the risk associated with SPS. The presence of antegrade PBF through the MPA, at initial and staged operations, did not significantly influence survival to Fontan operation. PMID- 26145768 TI - Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation. AB - OBJECTIVE: Vascular function is very important for maintaining circulation after cardiac surgery. Circulating microparticles (MPs) generated in various diseases play important roles in causing inflammation, coagulation, and vascular injury. However, the impact of MPs generated from patients who have valvular heart disease (VHD), before and after cardiac surgery, on vascular function remains unknown. This study is designed to investigate the impact of such MPs on vasodilation. METHODS: Microparticles were isolated from age-matched healthy subjects and patients who had VHD, before cardiac surgery, and at 12 hours and 72 hours afterward. The number of MPs was measured and compared. Effects evaluated were of the impact of MPs on: vasodilation of mice aorta; the phosphorylation and expression of Akt, endothelial nitric oxide synthase (eNOS), protein kinase C betaII (PKC-betaII), and p70 ribosomal protein S6 kinase (p70S6K); expression of caveolin-1; the association of eNOS with heat shock protein 90 (HSP90); and generation of nitric oxide and superoxide anion of human umbilical vein endothelial cells. RESULTS: Compared with the healthy subjects, VHD patients had significantly higher levels of circulating MPs and those MPs before cardiac surgery can: impair endothelium-dependent vasodilation; inhibit phosphorylation of Akt and eNOS; increase activation of PKC-betaII and p70S6K; enhance expression of caveolin-1; reduce the association of HSP90 with eNOS; decrease nitric oxide production, and increase superoxide anion generation. These deleterious effects were even stronger in postoperative MPs. CONCLUSIONS: Our data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively. PMID- 26145769 TI - Functional network centrality in obesity: A resting-state and task fMRI study. AB - Obesity is associated with structural and functional alterations in brain areas that are often functionally distinct and anatomically distant. This suggests that obesity is associated with differences in functional connectivity of regions distributed across the brain. However, studies addressing whole brain functional connectivity in obesity remain scarce. Here, we compared voxel-wise degree centrality and eigenvector centrality between participants with obesity (n=20) and normal-weight controls (n=21). We analyzed resting state and task-related fMRI data acquired from the same individuals. Relative to normal-weight controls, participants with obesity exhibited reduced degree centrality in the right middle frontal gyrus in the resting-state condition. During the task fMRI condition, obese participants exhibited less degree centrality in the left middle frontal gyrus and the lateral occipital cortex along with reduced eigenvector centrality in the lateral occipital cortex and occipital pole. Our results highlight the central role of the middle frontal gyrus in the pathophysiology of obesity, a structure involved in several brain circuits signaling attention, executive functions and motor functions. Additionally, our analysis suggests the existence of task-dependent reduced centrality in occipital areas; regions with a role in perceptual processes and that are profoundly modulated by attention. PMID- 26145789 TI - Could plant extracts have enabled hominins to acquire honey before the control of fire? AB - Honey is increasingly recognized as an important food item in human evolution, but it remains unclear whether extinct hominins could have overcome the formidable collective stinging defenses of honey bees during honey acquisition. The utility of smoke for this purpose is widely recognized, but little research has explored alternative methods of sting deterrence such as the use of plant secondary compounds. To consider whether hominins could have used plant extracts as a precursor or alternative to smoke, we review the ethnographic, ethnobotanical, and plant chemical ecology literature to examine how humans use plants in combination with, and independently of, smoke during honey collection. Plant secondary compounds are diverse in their physiological and behavioral effects on bees and differ fundamentally from those of smoke. Plants containing these chemicals are widespread and prove to be remarkably effective in facilitating honey collection by honey hunters and beekeepers worldwide. While smoke may be superior as a deterrent to bees, plant extracts represent a plausible precursor or alternative to the use of smoke during honey collection by hominins. Smoke is a sufficient but not necessary condition for acquiring honey in amounts exceeding those typically obtained by chimpanzees, suggesting that significant honey consumption could have predated the control of fire. PMID- 26145790 TI - Age and comorbidities deeply impact on clinical outcome of patients with myelodysplastic syndromes. AB - BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients. METHODS: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed. Comorbidities were evaluated according to HCT-CI and MDS-CI comorbidity indexes. Overall survival (OS) and the probability of death among patients who did not develop acute myeloid leukemia (NLD cumulative incidence) were analyzed. RESULTS: Comorbidities were seen in 177 (55.7%) patients. An older age (>75 y) had a significant negative impact on OS (p=0.008). HCT-CI was not associated with OS. MDS-CI was of prognostic significance (p=0.001), but the association was limited to pts with IPSS or IPSS-R "lower risk". In multivariate analysis, MDS-CI remained an independent factor associated with OS and with an increased risk of NLD both when controlling for IPSS (p=0.019 and p=0.001, respectively) and for IPSS-R (p=0.048 and p=0.002, respectively). CONCLUSIONS: Evaluation of age and comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporated to current prognostic scores. PMID- 26145812 TI - Learning from the past to build the future. PMID- 26145791 TI - Two-photon directed evolution of green fluorescent proteins. AB - Directed evolution has been used extensively to improve the properties of a variety of fluorescent proteins (FPs). Evolutionary strategies, however, have not yet been used to improve the two-photon absorption (2PA) properties of a fluorescent protein, properties that are important for two-photon imaging in living tissues, including the brain. Here we demonstrate a technique for quantitatively screening the two-photon excited fluorescence (2PEF) efficiency and 2PA cross section of tens of thousands of mutant FPs expressed in E. coli colonies. We use this procedure to move EGFP through three rounds of two-photon directed evolution leading to new variants showing up to a 50% enhancement in peak 2PA cross section and brightness within the near-IR tissue transparency wavelength range. PMID- 26145788 TI - Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer. AB - The humoral innate immune system is composed of three major branches, complement, coagulation, and natural antibodies. To persist in the host, pathogens, such as bacteria, viruses, and cancers must evade parts of the innate humoral immune system. Disruptions in the humoral innate immune system also play a role in the development of autoimmune diseases. This review will examine how Gram positive bacteria, viruses, cancer, and the autoimmune conditions systemic lupus erythematosus and anti-phospholipid syndrome, interact with these immune system components. Through examining evasion techniques it becomes clear that an interplay between these three systems exists. By exploring the interplay and the evasion/disruption of the humoral innate immune system, we can develop a better understanding of pathogenic infections, cancer, and autoimmune disease development. PMID- 26145813 TI - Electrochemical characterization of MC3T3-E1 cells cultured on gammaTiAl and Ti 6Al-4V alloys. AB - Electrochemical impedance spectroscopy (EIS) was used to study the behavior of MC3T3-E1 cells cultured in an alphaMEM+FBS solution on two Ti-based alloys (Ti 6Al-4V and gammaTiAl) for 4, 7 and 14 days. EIS measurements were carried out at an open-circuit potential in a 1 mHz to 100 kHz frequency range. Results indicate a general increase in impedance on the Ti alloy surfaces with cells as a function of time. Bode plots indicate changes corresponding to the passive oxide film, adsorption of proteins and cell tissue on surfaces with the passage of time. Normal cellular activity based on the polygonal morphology, with long and fine cytoplasmic prolongations of the cells on Ti-6Al-4V and gammaTiAl was observed from SEM images. Similarly, mineralization nodules corresponding to cell differentiation associated with the osseogenetic process were observed confirmed by Alizarin Red S staining. Immunofluorescence analysis to detect the presence of collagen Type I showed an increase in the segregation of collagen as a function of time. The impedance values obtained from EIS testing are indicative of the corrosion protection offered to the Ti alloy substrates by the cell layer. This study shows that gammaTiAl has better corrosion resistance than that of Ti-6Al-4V in the alphaMEM+FBS environment in the presence of MC3T3-E1 cells. PMID- 26145815 TI - The effect of temperature on electrochemically driven denaturation monitored by SERS. AB - Scanning the electrochemical potential negative results in the gradual denaturation of dsDNA immobilised at a nanostructure gold electrode, the DNA melting is monitored by SERS. We demonstrate the effect of the experimental temperature on the electrochemically driven melting (E-melting) by carrying out experiments between 10 and 28 degrees C using two DNA duplexes (20 and 21 base pairs). Significant temperature dependence for both the melting potentials, Em, and the steepness of the melting curves was found over the range 10 to 18 degrees C. Above 18 degrees C the results were found to be independent of temperature. The relative temperature insensitivity of the melting potentials above 18 degrees C is advantageous for the application of the electrochemically driven melting technique because precise temperature control is not necessary for measurements that are carried out around room temperature. Conversely temperature dependence below 18 degrees C offers a way to improve discrimination for highly similar DNA sequences. PMID- 26145814 TI - Electrochemical characterization of microbial bioanodes formed on a collector/electrode system in a highly saline electrolyte. AB - Bioanodes were formed with electrodes made of carbon felt and equipped with a titanium electrical collector, as commonly used in microbial fuel cells. Electrochemical impedance spectroscopy (EIS) performed on the abiotic electrode system evidenced two time constants, one corresponding to the "collector/carbon felt" contact, the other to the "carbon felt/solution" interface. Such a two time constant system was characteristics of the two-material electrode, independent of biofilm presence. EIS was then performed during the bioanode formation around the constant applied potential of 0.1 V/SCE. The equivalent electrical model was similar to that of the abiotic system. Due to the high salinity of the electrolyte (45 g.L(-1) NaCl) the electrolyte resistance was always very low. The bioanode development induced kinetic heterogeneities that were taken into account by replacing the pure capacitance of the abiotic system by a constant phase element for the "carbon felt/solution" interface. The current increase from 0 to 20.6 A.m(-2) was correlated to the considerable decrease of the charge transfer resistance of the "carbon felt/solution" interface from 2.4 10(4) to 92 Omega.cm(2). Finally, EIS implemented at 0.4 V/SCE showed that the limitation observed at high potential values was not related to mass transfer but to a biofilm-linked kinetics. PMID- 26145816 TI - Synopsis of the 4th Biannual Proteomic Forum: PhD student's insight. PMID- 26145818 TI - Synthesis and biological evaluation of isoflavone amide derivatives with antihyperlipidemic and preadipocyte antiproliferative activities. AB - A series of isoflavone amides were designed with isoflavone in place of the scaffold of 2-arylbenzoxazole as cholesterol ester transfer protein (CETP) inhibitors. Twelve new compounds were synthesized, and their inhibitory activities of CETP and preadipocyte proliferation were assayed. The hypolipidemic potency of the most effective compound HY-2c was further tested in vivo by hamster. The results indicate that HY-2c exhibited favorable antihyperlipidemic and preadipocyte antiproliferative activities. PMID- 26145819 TI - Stereoselective synthesis and pharmacological evaluation of [4.3.3]propellan-8 amines as analogs of adamantanamines. AB - Amantadine (1) exerts its anti-Parkinson effects by inhibition of the NMDA associated cation channel and its antiviral activity by inhibition of the M2 protein channel of influenza A viruses. Herein the synthesis, NMDA receptor affinity and anti-influenza activity of analogous propellanamines 3 are reported. The key steps in the synthesis of the diastereomeric propellanamines syn-3 and anti-3 are diastereoselective reduction of the ketone 7 with L-Selectride to give anti-11, Mitsunobu inversion of the alcohol anti-13 into syn-13, and SN2 substitution of diastereomeric mesylates syn-14 and anti-14 with NaN3. The affinity of the propellanamines syn-3 and anti-3 to the PCP binding site of the NMDA receptor is similar to that of amantadine (Ki=11 MUM). However, both propellanamines syn-3 and anti-3 do not exhibit activity against influenza A viruses. Compared to amantadine (1), the structurally related propellanamines syn 3 and anti-3 retain the NMDA antagonistic activity but loose the antiviral activity. PMID- 26145820 TI - Cloning, characterization and anion inhibition studies of a new gamma-carbonic anhydrase from the Antarctic bacterium Pseudoalteromonas haloplanktis. AB - A new gamma-class carbonic anhydrase (CA, EC 4.2.1.1) was cloned, purified and characterized from the Antarctic bacterium Pseudoalteromonas haloplanktis, PhaCAgamma. The enzyme has a medium-low catalytic activity for the physiologic reaction of CO2 hydration to bicarbonate and protons, with a kcat of 1.4*10(5)s( 1) and a kcat/Km of 1.9*10(6)M(-1)s(-1). An anion inhibition study of PhaCAgamma with inorganic anions and small molecule inhibitors is also reported. Many anions present in sea water, such as chloride, fluoride, sulfate, iodide, but also others such as azide, perchlorate and tetrafluoroborate did not inhibit this enzyme. Pseudohalides such as cyanate, thiocyanate, cyanide, selenocyanide, and also bicarbonate, nitrate, nitrite and many complex inorganic anions showed inhibition in the millimolar range (KI in the range of 1.7-9.3mM). The best PhaCAgamma inhibitors detected in this study were diethyldithiocarbamate (KI of 0.96 mM) as well as sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid (KI in the range of 82-91 MUM). Since gamma-CAs are poorly understood at this moment, being present in carboxysomes and thus involved in photosynthesis, this study may be relevant for a better understanding of these processes in Antarctic bacteria/cyanobacteria. PMID- 26145817 TI - Synthesis, F-18 radiolabeling, and microPET evaluation of 3-(2,4-dichlorophenyl) N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines as ligands of the corticotropin-releasing factor type-1 (CRF1) receptor. AB - A series of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5 a]pyrimidin-7-amines were synthesized and evaluated as potential positron emission tomography (PET) tracers for the corticotropin-releasing factor type-1 (CRF1) receptor. Compounds 27, 28, 29, and 30 all displayed high binding affinity (?1.2 nM) to the CRF1 receptor when assessed by in vitro competition binding assays at 23 degrees C, whereas a decrease in affinity (?10-fold) was observed with compound 26. The logP7.4 values of [(18)F]26-[(18)F]29 were in the range of ~2.2-2.8 and microPET evaluation of [(18)F]26-[(18)F]29 in an anesthetized male cynomolgus monkey demonstrated brain penetrance, but specific binding was not sufficient enough to differentiate regions of high CRF1 receptor density from regions of low CRF1 receptor density. Radioactivity uptake in the skull, and sphenoid bone and/or sphenoid sinus during studies with [(18)F]28, [(18)F]28-d8, and [(18)F]29 was attributed to a combination of [(18)F]fluoride generated by metabolic defluorination of the radiotracer and binding of intact radiotracer to CRF1 receptors expressed on mast cells in the bone marrow. Uptake of [(18)F]26 and [(18)F]27 in the skull and sphenoid region was rapid but then steadily washed out which suggests that this behavior was the result of binding to CRF1 receptors expressed on mast cells in the bone marrow with no contribution from [(18)F]fluoride. PMID- 26145821 TI - Inhibition studies of bacterial, fungal and protozoan beta-class carbonic anhydrases with Schiff bases incorporating sulfonamide moieties. AB - A series of new Schiff bases derived from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide containing either a hydrophobic or a hydrophilic tail, have been investigated as inhibitors of three beta-carbonic anhydrases (CA, EC 4.2.1.1) from three different microorganisms. Their antifungal, antibacterial and antiprotozoan activities have been determined against the pathogenic fungus Cryptococcus neoformans, the bacterial pathogen Brucella suis and the protozoan parasite Leishmania donovani chagasi, responsible for Leishmaniasis. The results of these inhibition studies show that all three enzymes were efficiently inhibited by the Schiff base sulfonamides with KI values in the nanomolar or submicromolar range, depending on the nature of the tail, coming from the aryl/heteroaryl moiety present in the starting aldehyde employed in the synthesis. Furthermore, the compounds hereby investigated revealed high beta-CAs selectivity over the ubiquitous, physiologically relevant and off-target human isoforms (CA I and II) and to be more potent as antifungal and antibacterial than as antiprotozoan potential drugs. PMID- 26145822 TI - Studies on the preferred uracil-adenine base pair at the cleavage site of 10-23 DNAzyme by functional group modifications on adenine. AB - 10-23 DNAzyme is capable of catalytically cleaving RNA substrates with the preferred cleavage sites rAU and rGU, in which the common base pair U-dA0 forms between the substrate and the DNAzyme in the cleavage reaction. Here its conservation was studied with base modifications on dA and extra functional groups introduced. The nitrogen atom at 7- or 8-position of adenine was demonstrated to be equally important for the cleavage reaction, although it is not related to the thermal stability of the base pair. Deletion of 6-amino group led to decreased stability of the base pair and a slight slower reaction rate. Extra functional groups through 6-amino group were not favorably accommodated in the cleavage site. From these modifications at the level of functional groups, it demonstrated that the base pair U-dA0 not only contributes to the recognition and binding stability, but also it is involved in the active catalytic center by its functional groups and base stacking. This kind of chemical modifications with 7 substituted 8-aza-7-deaza-2'-deoxyadenosine at dA0 is favorable for the introduction of signal molecules for mechanistic studies and biological applications, without significant loss of the catalytic function and structural destruction. PMID- 26145823 TI - Design and synthesis of a potent inhibitor of class 1 DYRK kinases as a suppressor of adipogenesis. AB - Dysregulation of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) has been demonstrated in several pathological conditions, including Alzheimer's disease and cancer progression. It has been recently reported that a gain of function-mutation in the human DYRK1B gene exacerbates metabolic syndrome by enhancing obesity. In the previous study, we developed an inhibitor of DYRK family kinases (INDY) and demonstrated that INDY suppresses the pathological phenotypes induced by overexpression of DYRK1A or DYRK1B in cellular and animal models. In this study, we designed and synthesized a novel inhibitor of DYRK family kinases based on the crystal structure of the DYRK1A/INDY complex by replacing the phenol group of INDY with dibenzofuran to produce a derivative, named BINDY. This compound exhibited potent and selective inhibitory activity toward DYRK family kinases in an in vitro assay. Furthermore, treatment of 3T3-L1 pre-adipocytes with BINDY hampered adipogenesis by suppressing gene expression of the critical transcription factors PPARgamma and C/EBPalpha. This study indicates the possibility of BINDY as a potential drug for metabolic syndrome. PMID- 26145824 TI - Visual Field Preservation in Surgery of Occipital Arteriovenous Malformations: A Prospective Study. AB - OBJECTIVE: We reviewed our prospective study of patients with occipital arteriovenous malformations (AVMs) to assess whether the display of optic radiation diffusion tensor imaging (DTI) during neuronavigation-guided surgery can reduce the severity of postoperative visual field deficits (VFDs) and to evaluate the factors associated with visual field preservation. METHODS: Forty six consecutive patients with occipital AVMs were randomized in our study. DTI of the optic radiation was displayed during neuronavigation surgery in 24 patients. The other 22 patients were treated surgically without neuronavigation. Modified Rankin Scale (mRS) scores and visual fields were evaluated preoperatively, immediately after surgery, and at the last follow-up. RESULTS: The patients' baseline characteristics and AVM features were statistically similar between the 2 surgical groups. The postoperative obliteration rate was 100%. The postoperative mRS scores did not differ between the 2 groups (P > 0.05). Preexisting VFDs were more common (P = 0.00004) in patients who bled than in those with unruptured AVMs. The application of DTI-incorporated neuronavigation reduced the frequency and severity of postoperative VFDs (P = 0.013 and 0.001, respectively). Visual fields were more likely to be preserved in patients with an AVM >5 mm from the optic radiation (P = 0.025). CONCLUSIONS: A history of hemorrhage is an independent risk factor for VFDs associated with occipital AVMs. Although not showing superiority in postoperative mRS, functional MRI navigation guided surgery may help to radically resect occipital AVMs and preserve patient visual fields. A 5-mm distance from the optic radiation may be a suitable safety margin for visual field preservation. PMID- 26145825 TI - Neuroplasticity and Brachial Plexus Injury. PMID- 26145826 TI - Giant Leaking Colloid Cyst Presenting with Aseptic Meningitis: Review of the Literature and Report of a Case. AB - BACKGROUND: Colloid cysts are benign third ventricle lesions that need to be diagnosed correctly because of their association with sudden death. Chemical or aseptic meningitis is a rare presentation of a colloid cyst. METHODS: We present a case of a 69-year-old man with fever, alteration of mental status, and meningismus. Microbiological examination of the cerebrospinal fluid revealed aseptic meningitis. Brain imaging revealed a third ventricular colloid cyst with hydrocephalus. RESULTS: The tumor was resected via endoscopic intervention. There were no persistent operative complications related to the endoscopic procedure. CONCLUSIONS: Chemical or aseptic meningitis is an unusual clinical manifestation of a colloid cyst, complicating the differential diagnosis, especially in the elderly. PMID- 26145827 TI - Does Trauma Have a Major Role in Ossified Posterior Longitudinal Ligament and Should We Perform Fusion in Every Case? PMID- 26145828 TI - Simulation in Spinal Surgery and the Transition from Novice to Expert. PMID- 26145829 TI - To Intervene or Not to Intervene in Chronic Cerebral Ischemia: Endovascular Revascularization. PMID- 26145830 TI - The adverse outcome pathway for rodent liver tumor promotion by sustained activation of the aryl hydrocarbon receptor. AB - An Adverse Outcome Pathway (AOP) represents the existing knowledge of a biological pathway leading from initial molecular interactions of a toxicant and progressing through a series of key events (KEs), culminating with an apical adverse outcome (AO) that has to be of regulatory relevance. An AOP based on the mode of action (MOA) of rodent liver tumor promotion by dioxin-like compounds (DLCs) has been developed and the weight of evidence (WoE) of key event relationships (KERs) evaluated using evolved Bradford Hill considerations. Dioxins and DLCs are potent aryl hydrocarbon receptor (AHR) ligands that cause a range of species-specific adverse outcomes. The occurrence of KEs is necessary for inducing downstream biological responses and KEs may occur at the molecular, cellular, tissue and organ levels. The common convention is that an AOP begins with the toxicant interaction with a biological response element; for this AOP, this initial event is binding of a DLC ligand to the AHR. Data from mechanistic studies, lifetime bioassays and approximately thirty initiation-promotion studies have established dioxin and DLCs as rat liver tumor promoters. Such studies clearly show that sustained AHR activation, weeks or months in duration, is necessary to induce rodent liver tumor promotion--hence, sustained AHR activation is deemed the molecular initiating event (MIE). After this MIE, subsequent KEs are 1) changes in cellular growth homeostasis likely associated with expression changes in a number of genes and observed as development of hepatic foci and decreases in apoptosis within foci; 2) extensive liver toxicity observed as the constellation of effects called toxic hepatopathy; 3) cellular proliferation and hyperplasia in several hepatic cell types. This progression of KEs culminates in the AO, the development of hepatocellular adenomas and carcinomas and cholangiolar carcinomas. A rich data set provides both qualitative and quantitative knowledge of the progression of this AOP through KEs and the KERs. Thus, the WoE for this AOP is judged to be strong. Species-specific effects of dioxins and DLCs are well known--humans are less responsive than rodents and rodent species differ in sensitivity between strains. Consequently, application of this AOP to evaluate potential human health risks must take these differences into account. PMID- 26145831 TI - Bayesian evaluation of a physiologically-based pharmacokinetic (PBPK) model of long-term kinetics of metal nanoparticles in rats. AB - Biomathematical modeling quantitatively describes the disposition of metal nanoparticles in lungs and other organs of rats. In a preliminary model, adjustable parameters were calibrated to each of three data sets using a deterministic approach, with optimal values varying among the different data sets. In the current effort, Bayesian population analysis using Markov chain Monte Carlo (MCMC) simulation was used to recalibrate the model while improving assessments of parameter variability and uncertainty. The previously-developed model structure and some physiological parameter values were modified to improve physiological realism. The data from one of the three previously-identified studies and from two other studies were used for model calibration. The data from the one study that adequately characterized mass balance were used to generate parameter distributions. When data from a second study of the same nanomaterial (iridium) were added, the level of agreement was still acceptable. Addition of another data set (for silver nanoparticles) led to substantially lower precision in parameter estimates and large discrepancies between the model predictions and experimental data for silver nanoparticles. Additional toxicokinetic data are needed to further evaluate the model structure and performance and to reduce uncertainty in the kinetic processes governing in vivo disposition of metal nanoparticles. PMID- 26145832 TI - Cloning, expression and structural stability of a cold-adapted beta-galactosidase from Rahnella sp. R3. AB - A novel gene was isolated for the first time from a psychrophilic gram-negative bacterium Rahnella sp. R3. The gene encoded a cold-adapted beta-galactosidase (R beta-Gal). Recombinant R-beta-Gal was expressed in Escherichia coli BL21 (DE3), purified and characterized. R-beta-gal belongs to the glycosyl hydrolase family 42. Circular dichroism spectrometry of the structural stability of R-beta-Gal with respect to temperature indicated that the secondary structures of the enzyme were stable to 45 degrees C. In solution, the enzyme was a homo-trimer and was active at temperatures as low as 4 degrees C. The enzyme did not require the presence of metal ions to be active, but Mg(2+), Mn(2+), and Ca(2+) enhanced its activity slightly, whereas Fe(3+), Zn(2+) and Al(3+) appeared to inactive it. The purified enzyme displayed K(m) values of 6.5 mM for ONPG and 2.2mM for lactose at 4 degrees C. These values were lower than the corresponding K(m)s reported for other cold-adapted beta-Gals. PMID- 26145833 TI - Purification and characterization of an extracellular uricase from a new isolate of Sphingobacterium thalpophilum (VITPCB5). AB - An extracellular uricase producing bacterium (VITPCB5) was isolated from soil of the duck farm near Chidambaram, Tamilnadu, India and it was identified based on its 16S rRNA as Sphingobacterium thalpophilum. Uric acid was used as an effective inducer. The enzyme kinetics was studied using uric acid as a substrate. The Km and Vmax for the enzyme was found to be 0.28mM and 0.92MUM/minml, respectively. Maximum uricase production was observed when lactose was used as a carbon source. Among the nitrogen sources tested, urea gave the maximum uricase production. The enzyme was successfully purified using a weak cation exchange convective interaction media carboxy methyl (CIM-CM) monolith column with a recovery of 79.7%+/-0.1 and 14.2+/-1.8-fold purification. The optimal reaction temperature of the enzyme was observed between 25 and 45 degrees C. The pH optimum of the enzyme was 8.0. The enzyme activity was enhanced by copper and partially inhibited by calcium, iron, zinc and nickel ions. Treatment with ethylene diamine tetraacetic acid completely inhibited the enzyme activity. The in-gel trypsin digested peptides of 48-kDa uricase when analyzed using mass spectrometry, gave 32% sequence coverage with the uricase (30-kDa) from Cyberlindnera jadinii. PMID- 26145834 TI - Definition and expression in E. coli of large fragments from the human lipid kinase phosphatidylinositol 4-kinase type III alpha, and purification of a 1100 residue N-terminal module. AB - The eukaryotic lipid kinase phosphatidylinositol 4-kinase III alpha (PI4KA in higher eukaryotes) is a ubiquitous enzyme that synthesizes the plasma membrane pool of phosphatidylinositol 4-phosphate. This important phosphoinositide has key roles in different signalization pathways, vesicular traffic and cellular compartment identity. Moreover, human PI4K4A is an essential factor for hepatitis C virus replication. PI4KA is a large protein (2102 residues for human PI4KA) with the kinase domain making up the ca 400 C-terminal residues. There is essentially no structural information about the 1500N-terminal residues and no clue as to the function of most of this region of PI4KA. In this report, we use computational methods in order to delineate fragments of human PI4KA amenable to soluble production in Escherichia coli. We clone and express these fragments as GST-fusions and evaluate the soluble fraction of each protein. Finally, we produce and purify to homogeneity a 1100-residue PI4KA N-terminal fragment. Our results further suggest that PI4KA can be described as a two-module protein. They open the way to structural characterization of the N-terminal regulatory module of PI4KA. PMID- 26145835 TI - Volumetric gain of the human pancreas after left partial pancreatic resection: A CT-scan based retrospective study. AB - BACKGROUND/OBJECTIVES: Regeneration of the pancreas has been well characterized in animal models. However, there are conflicting data on the regenerative capacity of the human pancreas. The aim of the present study was to assess the regenerative capacity of the human pancreas. METHODS: In a retrospective study, data from patients undergoing left partial pancreatic resection at a single center were eligible for inclusion (n = 185). Volumetry was performed based on 5 mm CT-scans acquired through a 256-slice CT-scanner using a semi-automated software. RESULTS: Data from 24 patients (15 males/9 females) were included. Mean +/- SD age was 68 +/- 11 years (range, 40-85 years). Median time between surgery and the 1st postoperative CT was 9 days (range, 0-27 days; IQR, 7-13), 55 days (range, 21-141 days; IQR, 34-105) until the 2nd CT, and 191 days (range, 62-1902; IQR, 156-347) until the 3rd CT. The pancreatic volumes differed significantly between the first and the second postoperative CT scans (median volume 25.6 mL and 30.6 mL, respectively; p = 0.008) and had significantly increased further by the 3rd CT scan (median volume 37.9 mL; p = 0.001 for comparison with 1st CT scan and p = 0.003 for comparison with 2nd CT scan). CONCLUSIONS: The human pancreas shows a measurable and considerable potential of volumetric gain after partial resection. Multidetector-CT based semi-automated volume analysis is a feasible method for follow-up of the volume of the remaining pancreatic parenchyma after partial pancreatectomy. Effects on exocrine and endocrine pancreatic function have to be evaluated in a prospective manner. PMID- 26145836 TI - Pancreatic exocrine insufficiency following pancreatic resection. AB - BACKGROUND/OBJECTIVES: Untreated pancreatic exocrine dysfunction is associated with poor quality of life and reduced survival, but is difficult to diagnose following pancreatic resection. Many factors including the extent of the surgery, the health of the residual pancreas and the type of reconstruction must be considered. Patients remain undertreated, and consequently there is much debate to whether or not pancreatic enzyme replacement therapy should be routinely prescribed following pancreatic resection. METHODS: A review of the literature was undertaken to establish the incidence of PEI and factors identifying treatment. RESULTS: Forty two to forty five percent of patients undergoing pancreatico-duodenectomy (PD) experience pancreatic exocrine insufficiency pre operatively, whilst the post-operative incidence is 56-98% in PD, and 12-80% following distal and central pancreatectomy. CONCLUSIONS: Routine use of pancreatic enzyme replacement should be considered at a starting dose of 50 to 75,000 units lipase with meals and 25,000 to 50,000 units with snacks in this patient group. Patients who have had a central or distal pancreatectomy should be individually assessed for pancreatic exocrine insufficiency in the post operative period, with those undergoing extensive resection most likely to experience insufficiency. Patients who fail to respond to pancreatic enzyme replacement therapy should be referred to a specialist dietitian, be advised on dose adjustment, and undergo investigation to exclude other gastro-intestinal pathology, including small bowel bacterial overgrowth and bile acid malabsorption. PMID- 26145837 TI - Conventional versus contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration for diagnosis of solid pancreatic lesions: A prospective randomized trial. AB - OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) has been used to diagnose solid pancreatic lesions (SPLs). The aim of this study was to investigate the efficacy of CEH-EUS-guided fine-needle aspiration (CEH-EUS FNA) compared with that of conventional EUS-FNA for the diagnosis of SPLs. METHODS: Forty patients with solid pancreatic lesions who visited Fukushima Medical University between September 2013 and June 2014 were recruited for this prospective study. Twenty patients underwent CEH-EUS-FNA, and 20 patients underwent conventional EUS-FNA. The sampling rate, sensitivity, accuracy, and number of needle passes required to obtain sufficient samples were compared between the two groups. RESULTS: Patient characteristics, sampling rate, accuracy, and sensitivity were not significantly different between the two groups. The final diagnosis of patients who underwent CEH-EUS-FNA was pancreatic cancer in 19 and intraductal papillary mucinous carcinoma in one. Nineteen patients who underwent conventional EUS-FNA were finally diagnosed with pancreatic cancer and one was diagnosed as cancer of the common bile duct. There was a significant difference in the number of needle passes required. A sufficient sample was obtained on one needle pass in 60% (12/20) of CEH-EUS-FNA group compared with 25% (5/20) of the conventional EUS-FNA group. CONCLUSIONS: Fewer needle passes were required to obtain samples from solid pancreatic lesions using CEH-EUS-FNA than those required using conventional EUS-FNA. Therefore, CEH EUS-FNA may be more efficient and safer than conventional EUS-FNA for the diagnosis of solid pancreatic lesions. PMID- 26145884 TI - Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment. AB - The tumor-promoting role of macrophages has been firmly established in most cancer types. However, macrophage identity has been a matter of debate, since several levels of complexity result in considerable macrophage heterogeneity. Ontogenically, tissue-resident macrophages derive from yolk sac progenitors which either directly or via a fetal liver monocyte intermediate differentiate into distinct macrophage types during embryogenesis and are maintained throughout life, while a disruption of the steady state mobilizes monocytes and instructs the formation of monocyte-derived macrophages. Histologically, the macrophage phenotype is heavily influenced by the tissue microenvironment resulting in molecularly and functionally distinct macrophages in distinct organs. Finally, a change in the tissue microenvironment as a result of infectious or sterile inflammation instructs different modes of macrophage activation. These considerations are relevant in the context of tumors, which can be considered as sites of chronic sterile inflammation encompassing subregions with distinct environmental conditions (for example, hypoxic versus normoxic). Here, we discuss existing evidence on the role of macrophage subpopulations in steady state tissue and primary tumors of the breast, lung, pancreas, brain and liver. PMID- 26145885 TI - Internal Hernia as a Cause for Intestinal Obstruction in a Newborn. AB - BACKGROUND: An internal hernia is a rare cause of intestinal obstruction, which can occur at any age. Children most often develop an internal hernia due to a congenital defect in the mesentery. While some patients are asymptomatic, others present to medical attention with vague abdominal symptoms, an acute abdomen, or in shock. CASE REPORT: We report a case of a 5-day-old previously healthy baby who presented to our pediatric emergency department with bilious vomiting, grossly bloody stool, and abdominal distention. During an exploratory laparotomy, the patient was diagnosed with an internal hernia caused by a congenital mesenteric defect. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although internal hernia is an infrequent cause of intestinal obstruction in a newborn and requires emergent operative repair, it may be mistaken for other more common causes, such as necrotizing entercolitis, which are often managed medically. This case report aims to highlight some of the difficulties in diagnosis and key features that may assist the clinician in identifying these patients. PMID- 26145886 TI - Stercoral Colitis in Two Young Psychiatric Patients Presenting with Abdominal Pain. AB - BACKGROUND: Fewer than 150 cases of stercoral colitis have been reported in the literature. Stercoral colitis develops when feces impacts in the colon, resulting in increased luminal pressure, colon wall ulceration, and an inflammatory colitis. Patients are typically over the age of 60 years and have history of constipation. Mortality from colon perforation secondary to stercoral colitis is as high as 60%. CASE REPORT: We present two male patients, ages 26 and 35 years old, with history of psychiatric illness who presented with constipation and abdominal pain, who were found to have stercoral colitis on computed tomography. One patient developed stercoral perforation of the colon requiring emergent laparotomy. WHY SHOULD EMERGENCY PHYSICIANS BE AWARE OF THIS?: Stercoral colitis is a rare but potentially fatal etiology of abdominal pain that should be considered in young patients with history of constipation. PMID- 26145887 TI - Prophylaxis with human serum butyrylcholinesterase protects Gottingen minipigs exposed to a lethal high-dose of sarin vapor. AB - Serum-derived human butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a potential prophylactic nerve agent countermeasure. Previously, we reported the prophylactic efficacy of Hu BChE in Gottingen minipigs against a whole-body exposure to 4.1mg/m(3) of sarin (GB) vapor, which produced lethality over 60min. Since the toxicity of nerve agent is concentration-dependent, in the present study, we investigated the toxic effects of an almost 3-fold higher rate of GB vapor exposure and the ability of Hu BChE to protect minipigs against this exposure. Male minipigs were subjected to: (1) air exposure; (2) GB vapor exposure; or (3) pretreatment with 7.5mg/kg of Hu BChE by i.m. injection, 24h prior to whole-body exposure to 11.4mg/m(3) of GB vapor for 10min. Electrocardiogram, electroencephalogram, and pupil size were monitored throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB bound to red blood cells and plasma. A novel finding was that saline-treated animals exposed to GB vapor did not develop any seizures, but manifested a variety of cardiac and whole blood toxic signs and rapidly died due to respiratory failure. Strikingly, pre-treatment with 7.5mg/kg of Hu BChE not only prevented lethality, but also avoided all cardiac toxic signs manifested in the non-treated cohort. Thus, Hu BChE alone can serve as an effective prophylactic countermeasure versus a lethal high-dose exposure to GB vapor. PMID- 26145983 TI - The mechanism or mechanisms driving atopic asthma initiation: The infant respiratory microbiome moves to center stage. AB - Developments over the last 5 to 10 years, principally from studies on comprehensively phenotyped prospective birth cohorts, have highlighted the important role of viral respiratory tract infections during infancy and early childhood, particularly those occurring against a background of pre-existing sensitization to perennial aeroallergens, in driving the development of early onset atopic asthma. Although debate surrounding the mechanism or mechanisms governing this causal pathway remains intense, demonstration of the capacity of pretreatment with anti-IgE antibody to blunt seasonal virus-associated asthma exacerbations in children provides strong support for the underlying concept. However, emerging data appear set to further complicate this picture. Notably, a combination of culture-based studies and complementary population-wide bacterial metagenomic data suggests that parallel host-bacteria interactions during infancy might play an additional role in modulating this causal pathway, as well as contributing independently to pathogenesis. These and related issues surrounding development of immune competence during the crucial early postnatal period, when these pathways are maximally active, are discussed below. PMID- 26145982 TI - The allergy epidemics: 1870-2010. AB - Before the first description of hay fever in 1870, there was very little awareness of allergic disease, which is actually similar to the situation in prehygiene villages in Africa today. The best explanation for the appearance and subsequent increase in hay fever at that time is the combination of hygiene and increased pollen secondary to changes in agriculture. However, it is important to remember that the major changes in hygiene in Northern Europe and the United States were complete by 1920. Asthma in children did not start to increase until 1960, but by 1990, it had clearly increased to epidemic numbers in all countries where children had adopted an indoor lifestyle. There are many features of the move indoors that could have played a role; these include increased sensitization to indoor allergens, diet, and decreased physical activity, as well as the effects of prolonged periods of shallow breathing. Since 1990, there has been a remarkable increase in food allergy, which has now reached epidemic numbers. Peanut has played a major role in the food epidemic, and there is increasing evidence that sensitization to peanut can occur through the skin. This suggests the possibility that changes in lifestyle in the last 20 years could have influenced the permeability of the skin. Overall, the important conclusion is that sequential changes in lifestyle have led to increases in different forms of allergic disease. Equally, it is clear that the consequences of hygiene, indoor entertainment, and changes in diet or physical activity have never been predicted. PMID- 26145984 TI - Promising candidates for allergy prevention. AB - Recent advances in understanding environmental risk factors for allergic diseases in children have led to renewed efforts aimed at prevention. Factors that modify the probability of developing allergies include prenatal exposures, mode of delivery, diet, patterns of medication use, and exposure to pets and farm animals. Recent advances in microbial detection techniques demonstrate that exposure to diverse microbial communities in early life is associated with a reduction in allergic disease. In fact, microbes and their metabolic products might be essential for normal immune development. Identification of these risk factors has provided new targets for prevention of allergic diseases, and possibilities of altering microbial exposure and colonization to reduce the incidence of allergies is a promising approach. This review examines the rationale, feasibility, and potential effect for the prevention of childhood allergic diseases and explores possible strategies for enhancing exposure to beneficial microbes. PMID- 26145987 TI - Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice. AB - BACKGROUND: Recently, we developed a humanized mouse model of allergen-induced IgE-dependent gut inflammation in PBMC-engrafted immunodeficient mice. OBJECTIVE: In the present study, we wanted to investigate the role of regulatory T (Treg) cells and their activation status in this model. METHODS: Nonobese diabetic severe combined immunodeficiency-gammac(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or NaCl as control in the presence or absence of different concentrations of CD4(+)CD25(+) Treg cells of the same donor. After an additional allergen boost 1 week later, mice were challenged with the allergen rectally on day 21 and gut inflammation was monitored by a high-resolution video mini-endoscopic system evaluating translucency, granularity, fibrin production, vascularity, and stool. RESULTS: Allergen-specific human IgE in mouse sera, which was detectable only in PBMC plus allergen-treated mice, was strongly inhibited by coinjection of Treg cells at a ratio of at least 1:10. Consequently, the presence of Treg cells significantly decreased IgE-dependent allergen-induced gut inflammation after rectal allergen challenge. In addition, Treg cells reduced allergen-specific proliferation and cytokine production of recovered human CD4(+) T cells in vitro. Activation of Treg cells before injection further increased all inhibitory effects. Prevention of gut inflammation also occurred by the administration of glycoprotein A repetitions predominant, a molecule expressed by activated Treg cells, whereas its blockade completely abrogated inhibition by Treg cells. CONCLUSIONS: These results demonstrate that allergen-specific gut inflammation in human PBMC-engrafted mice can be avoided by enhancing the numbers or activity of autologous Treg cells, which is of great interest for therapeutic intervention of allergic diseases of the intestine. PMID- 26145988 TI - Hydrothermal stability investigation of micro- and mesoporous silica containing long-range ordered cobalt oxide clusters by XAS. AB - This work investigates the hydrothermal stability of cobalt doped silica materials with different Co/Si molar ratios (0, 0.05, 0.10, and 0.25). The resultant materials were characterized by N2 sorption and chemical structures by Raman and X-ray absorption spectroscopy before and after a harsh hydrothermal exposure (550 degrees C, 75 mol% vapour and 40 h). The cobalt silica materials showed a lower surface area loss from 48% to 12% with increasing Co/Si molar ratio from 0.05 to 0.25 and relatively maintaining their pore size distribution, while pure silica exhibited significant surface area reduction (80%) and pore size broadening. For low cobalt loading sample (Co/Si = 0.05), the cobalt was highly dispersed in the silica network in a tetrahedral coordination with oxygen and a small proportion of Co-Co interaction in the second shell. Long range order Co3O4 was observed when Co/Si molar ratio increased to 0.10 and 0.25. The hydrothermal exposure did not affect the local cobalt environments and no cobalt silicon interaction was observed by X-ray absorption spectroscopy. The hydrothermal stability of the silica matrix was attributed to the physical barrier of cobalt oxide in opposing densification and silica mobility under harsh hydrothermal conditions. PMID- 26145989 TI - Au(I)-catalyzed synthesis of 8-oxabicyclo[3.2.1]oct-2-enes and 9 oxabicyclo[3.3.1]nona-2,6-dienes from enynol via oxonium/Prins-type cyclization. AB - A sustainable and simple Au(I) catalytic system to synthesise 8 oxabicyclo[3.2.1]oct-2-enes and 9-oxabicyclo[3.3.1]nona-2,6-dienes from enynol via oxonium/Prins-type cyclization is described. The key advantages of this reaction are selectivity, good functional group tolerance and a new approach for synthesis of oxabicyclic and oxatricyclic systems. PMID- 26145985 TI - 100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology. AB - Current knowledge of molecules involved in immunology and allergic disease results from the significant contributions of x-ray crystallography, a discipline that just celebrated its 100th anniversary. The histories of allergens and x-ray crystallography are intimately intertwined. The first enzyme structure to be determined was lysozyme, also known as the chicken food allergen Gal d 4. Crystallography determines the exact 3-dimensional positions of atoms in molecules. Structures of molecular complexes in the disciplines of immunology and allergy have revealed the atoms involved in molecular interactions and mechanisms of disease. These complexes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands. The information derived from crystallographic studies provides insights into the function of molecules. Allergen function is one of the determinants of environmental exposure, which is essential for IgE sensitization. Proteolytic activity of allergens or their capacity to bind LPSs can also contribute to allergenicity. The atomic positions define the molecular surface that is accessible to antibodies. In turn, this surface determines antibody specificity and cross-reactivity, which are important factors for the selection of allergen panels used for molecular diagnosis and the interpretation of clinical symptoms. This review celebrates the contributions of x-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that influence the diagnosis and treatment of allergic diseases. PMID- 26145990 TI - [Make organ donation an act of an obligation ?]. PMID- 26145991 TI - [Virus outbreaks and health emergencies]. PMID- 26145992 TI - [Emerging infectious diseases today]. AB - Infectious diseases are inherent to humanity. Advances in medicine notably have ensured that some have been eradicated. However, today's world favours the emergence of these pathologies. Health professionals are on the frontline in promoting prevention actions. PMID- 26145993 TI - [Ebola virus disease and accredited specialist health institutions]. AB - Ebola virus disease (EVD) went in the space of a few months from being a forgotten tropical disease to a global "health emergency". The scope of this Ebola virus epidemic (Zaire strain), which has broken out in West Africa, its spread and the high number of deaths reported among frontline health workers are unprecedented. This article describes how a specialist hospital deals with imported cases of EVD. PMID- 26145994 TI - [Medical services at Paris-Charles-de-Gaulle airport]. AB - Charles-de-Gaulle airport in Roissy, a 3 400 hectare citadel, contains a multitude of airlines, service companies, businesses, retailers and public services, including firefighters, police officers, customs officers, ministers and medical teams. This article presents its missions, notably with regard to health services. PMID- 26145995 TI - [What response in the face of health emergencies?]. AB - Heat wave, extreme cold, air pollution, epidemics, nuclear plant accidents, production incidents in the pharmaceutical or agro-food sectors, bioterrorism, social movements: over the last thirty years, health emergencies have multiplied. What is the strategy to adopt? PMID- 26145996 TI - [Eprus, an agency to respond to health emergencies]. AB - The Health Emergency Preparedness and Response Agency (Eprus) was created by the French ministry in charge of the health. It manages on behalf of the state, human, pharmaceutical and logistical resources which can be used in the event of exceptional health situations, in France and abroad. PMID- 26145997 TI - [Promoting oral health in Roma families and children]. AB - The association Medecins du Monde, through its Missions France programmes, works to improve the state of health of marginalised populations in France. For these people, it seeks to favour access to care, rights and prevention. One such project has been set up in Nantes, aimed at Roma families. A young hospital nurse shares his experience of his voluntary work promoting oral health. PMID- 26145998 TI - [Favouring the work-life balance]. AB - Saint-Amand-les-Eaux general hospital, in the north of France, actively promotes quality of life at work for its staff. In 2014, during National Quality of Life at Work week, the hospital put in place a programme of activities encouraging a better work-life balance. PMID- 26145999 TI - [Calling patients on the eve of their day surgery procedure]. AB - In day surgery, the call on the eve of the procedure is a key stage in the patient's care pathway. Systematically carried out by the nurse, it helps to establish a relationship of trust with the nursing team. Through this exchange, the nurse ensures various aspects of the patient management are taken care of and optimises the organisation of the following day's programme. A team from Pau shares its practice. PMID- 26146000 TI - [Prevention of cot death in maternity hospitals]. AB - Part of the role of the child health nurse is to promote the health of infants and families in a public health community approach. She designs and implements health education actions. Raising parents' awareness of how to position newborns when they sleep and the prevention of cot death is a public health priority. PMID- 26146001 TI - [The nurse and care of the diabetic foot]. PMID- 26146002 TI - Fighting Ebola in Sierra Leone. AB - Sophie and Pierre have enrolled in the operational team of a humanitarian organisation for two months, in order to help contain the Ebola epidemic. They landed in Freetown, the capital of Sierra Leone, only yesterday. PMID- 26146003 TI - [The examinations at the bedside of the patient]. PMID- 26146004 TI - [Multiple sclerosis and therapeutic management]. PMID- 26146005 TI - [Nursing care, a fundamental tool]. PMID- 26146006 TI - Interaction of Hyaluronan with Cationic Nanoparticles. AB - The polysaccharide hyaluronan (HA) is a main component of peri- and extracellular matrix, and an attractive molecule for materials design in tissue engineering and nanomedicine. Here, we study the morphology of complexes that form upon interaction of nanometer-sized amine-coated gold particles with this anionic, linear, and regular biopolymer in solution and grafted to a surface. We find that cationic nanoparticles (NPs) have profound effects on HA morphology on the molecular and supramolecular scale. Quartz crystal microbalance (QCM-D) shows that depending on their relative abundance, cationic NPs promote either strong compaction or swelling of films of surface-grafted HA polymers (HA brushes). Transmission electron and atomic force microscopy reveal that the NPs do also give rise to complexes of distinct morphologies-compact nanoscopic spheres and extended microscopic fibers-upon interaction with HA polymers in solution. In particular, stable and hydrated spherical complexes of single HA polymers with NPs can be prepared when balancing the ionizable groups on HA and NPs. The observed self-assembly phenomena could be useful for the design of drug delivery vehicles and a better understanding of the reorganization of HA-rich synthetic or biological matrices. PMID- 26146008 TI - Unified mild reaction conditions for C2-selective Pd-catalysed tryptophan arylation, including tryptophan-containing peptides. AB - Pd-mediated C-H bond functionalisation protocols have been designed and developed on tryptophan derivatives and tryptophan-containing peptides. The examination of different arylation reactions (three sets of different conditions A-C), all of which are notable for their low temperatures (<=40 degrees C), allowed identification of unified and complementary synthetic approaches toward a series of functionalised tryptophan-containing products. Tryptophan-containing peptides demonstrated to be susceptible to aromatic oxidation were successfully and selectively modified through the application of diaryliodonium salts in good yields. PMID- 26146009 TI - Calculation of Membrane Lipid Ratios Using Single-Pixel Time-of-Flight Secondary Ion Mass Spectrometry Analysis. AB - Much evidence suggests that membrane domains, termed lipid rafts, which are enriched in sphingomyeline and cholesterol play important roles in the regulation of physiological and pathophysiological processes. A label-free quantitative imaging method for lipids is lacking at present. We report an algorithm which enables us to identify and calculate the percentages of the ingredients of lipid mixtures from single-pixel time-of-flight secondary ion mass spectrometry (TOF SIMS) spectra in model systems. The algorithm is based on a linear mixing model. Discriminant analysis is used to reduce the dimension of the data space. Calculations were separately performed for positive and negative ion mass spectra. Phosphatidylcholine and sphingomyeline which have identical headgroups and cannot be easily distinguished from another by positive ion mass spectra were included in the analysis. The algorithm outlined may more generally be used to calculate the percentages of ingredients of mixtures from spectra acquired by quite different methods such as X-ray photoelectron spectroscopy. PMID- 26146010 TI - Green tea extract improves the oxidative state of the liver and brain in rats with adjuvant-induced arthritis. AB - The purpose of the study was to evaluate the possible effects of the administration of a green tea extract on the oxidative state of the liver and brain of adjuvant-induced arthritic rats, a model for human rheumatoid arthritis. Daily doses of 250 mg kg(-1) (59.8 mg catechins per kg) for 23 days were administered. This treatment produced significant diminutions in protein and lipid damage in liver, brain and plasma. It also diminished the tissue ROS contents and increased the antioxidant capacity of the plasma. The antioxidant defenses, which are diminished by arthritis, were improved by the green tea treatment, as revealed by the restoration of the GSH and protein thiol levels and by the strong tendency for normalizing the activities of the antioxidant enzymes. The activity of glucose 6-phosphate dehydrogenase, which is increased by arthritis in the liver, was also almost normalized by the treatment. In conclusion, it can be said that green tea consumption is possibly beneficial for the liver and brain of patients suffering from rheumatoid arthritis because it attenuates the pronounced oxidative stress that accompanies the disease and, thus, diminishes the injury to lipids and proteins in both liver and brain. There are also indications that, in the liver, the green tea can contribute to normalize the metabolic functions that are substantially modified by arthritis. For example, the green tea normalized the activity of glucose 6-phosphate dehydrogenase, a key enzyme of an important metabolic route (pentose monophosphate pathway). It is expected that the green tea treatment is equally able to normalize the activity of other enzymes (e.g., glucokinase and glucose 6 phosphatase), a hypothesis to be tested by future work. PMID- 26146011 TI - Pembrolizumab for the treatment of melanoma. AB - The immune system plays a vital role in regulating tumor growth, and the oncology community has witnessed an exciting resurgence in clinical research to develop effective immunotherapeutic strategies. The utility of these strategies in advanced melanoma has been at the forefront of these developments. In particular, blockade of programmed cell death protein 1 (PD-1) in advanced melanoma has proven to be a most promising new anticancer strategy. Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that exerts its anti-tumor effect through blocking the interaction of the immune inhibitory molecule PD-1 with its ligands. Its effect has been most convincingly demonstrated in the setting of advanced melanoma, with growing evidence of clinical responses across a broad spectrum of other solid and hematological malignancies. PMID- 26146012 TI - Protoisomerization of indigo di- and monoimines. AB - Indigo di- and monoimines can be protonated to form stable salts in which the central C=C bond has isomerized from a trans to cis configuration. Deprotonation of these salts regenerates the neutral trans species. The protonation chemistry of indigo is also explored. PMID- 26146013 TI - Vestibular function after cochlear implant surgery. AB - OBJECTIVE: The aim of this study was to analyze vestibular function in cochlear implant (CI) patients for iatrogenic damage to vestibular function. METHODS: Prospective clinical study. Tertiary care audiological center. Twenty-five subjects receiving surgery for cochlear implantation during 2012 and 2013 were analyzed. Both vestibulo-ocular and vestibulo-spinal responses before and 2 months after CI surgery were evaluated using several tests: analysis of spontaneous nystagmus, head shaking test (HST), and head impulse test recorded by videooculography; caloric stimulation at 44 degrees and 30 degrees in both ears; cervical evoked myogenic potentials and static stabilometry. Residual cochlear function was tested by air-conduction pure-tone audiometry. RESULTS: Our tests showed damage to vestibular receptors after CI surgery in 12% of the patients; in particular, horizontal semicircular canal function and saccular function had lower responses after surgery. Audiometric results showed poorer thresholds after CI surgery. The static stabilometry results indicate good vestibulo-spinal responses and patients did not report disequilibrium nor postural deficit. CONCLUSION: All data suggest an efficient vestibular compensation mechanism in CI patients. PMID- 26146014 TI - Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice. AB - RATIONALE: The a2A-noradrenergic agonist guanfacine can decreases stress-induced smoking in female, but not male, human smokers. It is not known whether these effects are due to effects on mood regulation and/or result from nicotinic cholinergic interactions. OBJECTIVES: The objective of the study was to determine whether there are sex differences in the effect of guanfacine in tests of anxiolytic and antidepressant efficacy in mice at baseline and in a hypercholinergic model of depression induced by the acetylcholinesterase inhibitor physostigmine. METHODS: The effects of guanfacine were measured in the light/dark box, tail suspension, and the forced swim test in female and male C57BL/6J mice. In parallel, electrophysiological properties were evaluated in the prefrontal cortex, a critical brain region involved in stress responses. c-fos immunoreactivity was measured in other brain regions known to regulate mood. RESULTS: Despite a baseline sex difference in behavior in the forced swim test (female mice were more immobile), guanfacine had similar, dose-dependent, antidepressant-like effects in mice of both sexes (optimal dose, 0.15 mg/kg). An antidepressant-like effect of guanfacine was also observed following pre treatment with physostigmine. A sex difference in the paired-pulse ratio in the prefrontal cortex (PFC) (male, 1.4; female, 2.1) was observed at baseline that was normalized by guanfacine. Other brain areas involved in cholinergic control of depression-like behaviors, including the basolateral amygdala and lateral septum, showed sex-specific changes in c-fos expression. CONCLUSIONS: Guanfacine has a robust antidepressant-like effect and can reverse a depression-like state induced by increased acetylcholine (ACh) signaling. These data suggest that different brain areas are recruited in female and male mice, despite similar behavioral responses to guanfacine. PMID- 26146016 TI - Elevated reinforcing and motivational properties of alcohol at the end of the nocturnal period in sP rats. AB - RATIONALE: Sardinian alcohol-preferring (sP) rats displayed high sensitivity to time schedule and consumed intoxicating amounts of alcohol during the last portion of the dark phase of the light/dark cycle when exposed to daily drinking sessions of 1 h, with concurrent availability of multiple alcohol concentrations and unpredictability of time of alcohol access. OBJECTIVES: The present study investigated whether sensitivity of sP rats to time schedule extended to operant procedures of alcohol self-administration. METHODS: In experiment 1, three different alcohol solutions (10, 20, and 30%, v/v) were concurrently available under a fixed ratio 4 schedule of reinforcement and with unpredictable time schedule; water was available uncontingently. Experiments 2 and 3 assessed the sensitivity of the motivational properties of alcohol to time schedule; rats were exposed to (a) self-administration sessions under the progressive ratio (PR) schedule of reinforcement and (b) sessions of alcohol seeking under the extinction responding (ER) schedule. RESULTS: In experiment 1, number of lever responses and amount of self-administered alcohol were positively correlated with time of alcohol access during the dark phase. When the self-administration session occurred at the first and latest hours of the dark phase, the amount of self-administered alcohol averaged 0.95-1.0 and 1.55-1.65 g/kg, respectively. In experiments 2 and 3, values of breakpoint and ER for alcohol were approximately 50% higher when the sessions occurred at the last than first hour of the dark phase. CONCLUSIONS: The reinforcing and motivational properties of alcohol were sensitive to time schedule and stronger at the end of the dark phase. PMID- 26146015 TI - Histamine H1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers. AB - RATIONALE: Histamine H1 antagonists have hypnotic, appetite-promoting, and sedative side effects. Most second-generation antipsychotics have potent antagonistic effects on histamine H1 receptor (H1R). Positron emission tomography (PET) can measure the H1R occupancy (H1RO) in vivo, although there are no reports regarding antipsychotics. OBJECTIVES: We studied the H1RO of olanzapine and quetiapine in vivo with respect to their plasma concentrations and subjective drowsiness by performing human PET imaging studies with [(11)C]doxepin, a potent PET ligand of H1R. METHODS: Six healthy Japanese male volunteers were enrolled. Cross-randomized PET imaging was performed after a single oral administration of olanzapine (2.5 mg), quetiapine (25 mg), or placebo. PET data were analyzed by region of interest and voxel-by-voxel analysis. We concurrently measured plasma drug concentrations by liquid chromatography/tandem mass spectrometry and evaluated subjective sleepiness. RESULTS: The binding potential ratios of olanzapine and quetiapine in the cerebral cortex were significantly lower than that of the placebo. The H1RO values of olanzapine and quetiapine in the cortex were approximately 61-80 and 56-81%, respectively. The binding potential ratios of the drugs were significantly lower than that of the placebo in the dorsolateral prefrontal and lateral temporal cortices, and anterior and posterior cingulate gyri. The H1RO values in the cortex were significantly correlated with subjective sleepiness but not plasma drug concentrations. CONCLUSIONS: Olanzapine and quetiapine have high H1RO values in the human brain under their clinical minimum doses. This study provides a foundation of the properties by which new generation antipsychotics block the central histaminergic system in humans. PMID- 26146017 TI - The Integration of Sub-10 nm Gate Oxide on MoS2 with Ultra Low Leakage and Enhanced Mobility. AB - The integration of ultra-thin gate oxide, especially at sub-10 nm region, is one of the principle problems in MoS2 based transistors. In this work, we demonstrate sub-10 nm uniform deposition of Al2O3 on MoS2 basal plane by applying ultra-low energy remote oxygen plasma pretreatment prior to atomic layer deposition. It is demonstrated that oxygen species in ultra-low energy plasma are physically adsorbed on MoS2 surfaces without making the flakes oxidized, and is capable of benefiting the mobility of MoS2 flake. Based on this method, top-gated MoS2 transistor with ultrathin Al2O3 dielectric is fabricated. With 6.6 nm Al2O3 as gate dielectric, the device shows gate leakage about 0.1 pA/MUm(2) at 4.5 MV/cm which is much lower than previous reports. Besides, the top-gated device shows great on/off ratio of over 10(8), subthreshold swing (SS) of 101 mV/dec and a mobility of 28 cm(2)/Vs. With further investigations and careful optimizations, this method can play an important role in future nanoelectronics. PMID- 26146018 TI - Heat capacity peak at the quantum critical point of the transverse Ising magnet CoNb2O6. AB - The transverse Ising magnet Hamiltonian describing the Ising chain in a transverse magnetic field is the archetypal example of a system that undergoes a transition at a quantum critical point (QCP). The columbite CoNb2O6 is the closest realization of the transverse Ising magnet found to date. At low temperatures, neutron diffraction has observed a set of discrete collective spin modes near the QCP. Here, we ask if there are low-lying spin excitations distinct from these relatively high-energy modes. Using the heat capacity, we show that a significant band of gapless spin excitations exists. At the QCP, their spin entropy rises to a prominent peak that accounts for 30% of the total spin degrees of freedom. In a narrow field interval below the QCP, the gapless excitations display a fermion-like, temperature-linear heat capacity below 1 K. These novel gapless modes are the main spin excitations participating in, and affected by, the quantum transition. PMID- 26146019 TI - Salivary hormones and IgA in relation to physical performance in football. AB - Salivary biomarkers have shown to be useful to assess physiological stress in football, but their relationship with physical performance is unknown. The aims of this study were to investigate the effect of a football match on salivary cortisol, testosterone and immunoglobulin A (IgA) concentrations in elite footballers, and to examine the relationship of physical performance during the match to these biomarkers. Nine elite football players were assessed before, during and after a friendly international match. Physical performance during the match was measured by time-motion analysis, whilst salivary cortisol, testosterone and IgA were measured before and 10 min post-match. The results showed that players covered an average of 9463 +/- 458 m during the match. Salivary cortisol did not change post-match. Testosterone and IgA concentrations decreased by 30.6% and 74.5%, respectively. The testosterone/cortisol (T/C) ratio decreased by 64.2% after the match. Changes in testosterone concentrations correlated (r = 0.85) with distance covered. Pre- and post-match testosterone levels correlated with post-match IgA concentrations (r = 0.8 and 0.89, respectively). These results suggest that a football match induces catabolic stress as indicated by the decreased T/C ratio. It seems that footballers with smaller decreases in testosterone levels covered more distance and decreased their immune function less. PMID- 26146021 TI - Supramolecular chirality in self-assembled peptide amphiphile nanostructures. AB - Induced supramolecular chirality was investigated in the self-assembled peptide amphiphile (PA) nanosystems. Having shown that peptide chirality can be transferred to the covalently-attached achiral pyrene moiety upon PA self assembly, the chiral information is transferred to molecular pyrene via weak noncovalent interactions. In the first design of a supramolecular chiral system, the chromophore was covalently attached to a peptide sequence (VVAGH) via an epsilon-aminohexanoic acid spacer. Covalent attachment yielded a PA molecule self assembling into nanofibers. In the second design, the chromophore was encapsulated within the hydrophobic core of self-assembled nanofibers of another PA consisting of the same peptide sequence attached to lauric acid. We observed that supramolecular chirality was induced in the chromophore by PA assembly into chiral nanostructures, whether it was covalently attached, or noncovalently bound. PMID- 26146022 TI - Investigating the Complexation of the Pb(2+)/Bi(3+) Pair with Dipicolinate Cyclen Ligands. AB - The complexation properties toward Pb(2+) and Bi(3+) of the macrocyclic ligands 6,6'-((1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))dipicolinic acid (H2do2pa) and 6,6'-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7 diyl)bis(methylene))dipicolinic acid (H2Me-do2pa) have been investigated. A new three-step synthesis of H2do2pa following the bisaminal methodology has also been developed. The X-ray structures of [Pb(Me-do2pa)].6H2O and [Bi(Me do2pa)](NO3).H2O show that the two metal ions are eight-coordinated by the ligand. The two complexes exist as the racemic Delta(deltadeltadeltadelta)/Lambda(lambdalambdalambdalambda) mixture both in the solid state and in solution, as indicated by NMR and DFT studies. The stability constants of the lead(II) and bismuth(III) complexes of the two ligands were determined in 0.5 M KCl using potentiometric and spectrophotometric techniques. The stability constants determined for the complexes of Pb(2+) are relatively high (log KML = 16.44 and 18.44 for H2do2pa and H2Me-do2pa, respectively) and exceptionally high for the complexes of Bi(3+) (log KML = 32.0 and 34.2 for H2do2pa and H2Me-do2pa, respectively). The [Pb(Me-do2pa)] complex presents rather fast formation and very good kinetic inertness toward transchelation. Additionally, the [Bi(Me-do2pa)](+) complex was found to present a remarkably fast complexation rate (full complexation in ~2 min at pH 5.0, acetate buffer) and a very good kinetic inertness with respect to metal ion dissociation (half life of 23.9 min in 1 M HCl), showing promise for potential applications in alpha radioimmunotherapy. PMID- 26146023 TI - Local treatment of the inner ear: a study of three different polymers aimed for middle ear administration. AB - CONCLUSION: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. OBJECTIVES: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. METHOD: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. RESULTS: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration. PMID- 26146024 TI - Removal of chlorine gas by an amine functionalized metal-organic framework via electrophilic aromatic substitution. AB - Here we report the removal of chlorine gas from air via a reaction with an amine functionalized metal-organic framework (MOF). It is found that UiO-66-NH2 has the ability to remove 1.24 g of Cl2 per g of MOF via an electrophilic aromatic substitution reaction producing HCl, which is subsequently neutralized by the MOF. PMID- 26146025 TI - Effects of continuous positive airway pressure treatment on glucose metabolism in patients with obstructive sleep apnea. AB - A possible association between obstructive sleep apnea (OSA) and type 2 diabetes (T2DM) has been suggested. OSA could alter glucose metabolism, generating insulin resistance and favoring the development of T2DM. In addition, our greater understanding of intermediate disorders produced by intermittent hypoxia and sleep fragmentation, such as sympathetic activation, oxidative stress, systemic inflammation and alterations in appetite-regulating hormones, provides biological plausibility to this possible association. Nevertheless, there are still few data available about the consequences of suppressing apnea. Therefore, the objective of this review was to analyze current knowledge about the effect of continuous positive airway pressure (CPAP) on glucose metabolism. A global interpretation of the studies evaluated shows that CPAP could improve insulin resistance, and perhaps also glycemic control, in OSA patients who still have not developed diabetes. In addition, it seems possible that the effect of CPAP is still greater in patients with OSA and T2DM, particularly in those patients with more severe and symptomatic OSA, in those with poorer baseline glycemic control and with greater compliance and duration of CPAP treatment. In conclusion, although the current information available is limited, it suggests that apnea reversion by means of CPAP could improve the control of glucose metabolism. PMID- 26146020 TI - Tulane virus recognizes sialic acids as cellular receptors. AB - The recent discovery that human noroviruses (huNoVs) recognize sialic acids (SAs) in addition to histo-blood group antigens (HBGAs) pointed to a new direction in studying virus-host interactions during calicivirus infection. HuNoVs remain difficult to study due to the lack of an effective cell culture model. In this study, we demonstrated that Tulane virus (TV), a cultivable primate calicivirus, also recognizes SAs in addition to the previously known TV-HBGA interactions. Evidence supporting this discovery includes that TV virions bound synthetic sialoglycoconjugates (SGCs) and that treatment of TV permissive LLC-MK2 cells with either neuraminidases or SA-binding lectins inhibited TV infectivity. In addition, we found that Maackia amurensis leukoagglutinin (MAL), a lectin that recognizes the alpha-2,3 linked SAs, bound LLC-MK2 cells, as well as TV, by which MAL promoted TV infectivity in cell culture. Our findings further highlight TV as a valuable surrogate for huNoVs, particularly in studying virus-host interactions that may involve two host carbohydrate receptors or co-receptors for infection. PMID- 26146026 TI - Cardiovascular autonomic dysfunctions and sleep disorders. AB - Animal and human studies have shown that disorders of the autonomic nervous system may influence sleep physiology. Conversely, sleep disorders may be associated with autonomic dysfunctions. The current review describes the clinical presentation, supposed pathogenetic mechanisms and the diagnostic and prognostic implications of impaired cardiovascular autonomic control in sleep disorders. This dysfunction may result from a common pathogenetic mechanism affecting both autonomic cardiovascular control and sleep, as in fatal familial insomnia, or it may be mainly caused by the sleep disorder, as observed in obstructive sleep apnoea. For other sleep disorders, like primary insomnia, restless legs syndrome, narcolepsy type 1 and rapid eye movement sleep behaviour disorder, the causal link with the autonomic dysfunction and its possible impact on health remains unsettled. Given its clinical implications, most of the data available suggest that a systematic assessment of the association between sleep disorders and impaired autonomic control of the cardiovascular system is warranted. Understanding the mechanism of this association may also yield insights into the interaction between the autonomic nervous system and sleep. PMID- 26146027 TI - Pediatric OSAS: Oximetry can provide answers when polysomnography is not available. AB - Overnight polysomnography is the gold standard tool for the diagnosis of obstructive sleep apnea syndrome (OSAS) in habitually snoring children, but it is expensive and not always available. Nocturnal oximetry has been proposed as an abbreviated and low-cost testing modality for the diagnosis of OSAS. In this systematic review, 25 original articles were evaluated to: (i) summarize reference values of nocturnal oximetry parameters in healthy children; (ii) identify abnormal oximetry patterns that predict OSAS in habitually snoring children; (iii) delineate abnormalities in oximetry that can predict responses to treatment interventions for OSAS and potential complications. Nocturnal SpO2 drops <90%, more than two clusters of desaturation events (>=4%) and oxyhemoglobin desaturation (>=4%) index (ODI4) >2.2 episodes/h are unusual in children without OSAS. At least three clusters of desaturation events, and at least three SpO2 drops below 90% in a nocturnal oximetry recording are indicative of moderate-to-severe OSAS. An ODI4 >2 episodes/h combined with OSAS symptoms also exhibits high positive predictive value for apnea-hypopnea index >1 episode/h. Children without clusters of desaturation events have low risk of major respiratory complications following adenotonsillectomy. Thus, nocturnal oximetry emerges as a valuable tool that can facilitate treatment decisions when polysomnography is not available. PMID- 26146028 TI - Synthesis, structural, magnetic and phase-transition studies of the ferromagnetic La2CoMnO6 double perovskite by symmetry-adapted modes. AB - A powdered La2CoMnO6 double perovskite was synthesized by the solid-state reaction method, and its crystal structure was investigated by (mode crystallography) Rietveld analysis using X-ray and neutron powder diffraction data. La2CoMnO6 material is a monoclinic perovskite at room temperature, adopting the space group P21/n (a(-)a(-)b(+)), , c ~ 2ap and Z = 2. The P21/n phase can be described effectively by three distortion modes (GM4(+), X3(+), X5(+)) of the Fm3[combining macron]m (a(0)a(0)a(0)) parent phase. The comparative study of the material and those in the Ln2CoMnO6 and Ln2NiMnO6 families has shown a general trend in nearly all the materials, has served to select a common direction in the sub-space spanned by X5(+), tri-linearly coupled to the order parameters of the cubic to monoclinic first order phase transition. This direction has been used to parametrize the refinements and to perform reliable refinements in the high temperature intermediate distorted trigonal phase, R3[combining macron] (a(-)a( )a(-)), for which only one effectively acting irrep has been deduced: GM5(+), physically a tilt of the oxygen sharing octahedra of Co and Mn. Its temperature evolution up to the prototype cubic phase has been fitted in the framework of the Landau Theory of Phase Transitions, showing a behavior typical of a tricritical point. The low-temperature neutron powder diffraction data have served to solve the magnetic structure: three indistinguishable ferromagnetic models with the space groups P21/n and P2/n' are proposed. PMID- 26146029 TI - The cooperative adsorption properties of cetyl/amino-SBA-15 for 4-nonylphenol. AB - In this study, mesoporous SBA-15 bifunctionalized with cetyl and amino groups (cetyl/amino-SBA-15) was successfully prepared by a post-synthesis grafting method. Detailed characterization by XRD, FT-IR, N2 adsorption-desorption and elemental analysis confirmed that cetyl/amino-SBA-15 still retained a long-range ordered hexagonal mesostructure. Cetyl and aminopropyl groups were simultaneously functionalized on the surface of SBA-15. The adsorption capacity of cetyl/amino SBA-15 was much higher than the arithmetic sum of those of cetyl-SBA-15 and amino SBA-15 due to the cooperative effect of hydrogen bonding/electrostatic interaction between 4-nonylphenol (4-NP) and aminopropyl groups and hydrophobic interactions between 4-NP and cetyl groups. The effects of the dosage and mole ratio of cetyl and amino groups on the adsorption properties of cetyl/amino-SBA 15 for 4-NP were also investigated. Cetyl/amino-SBA-15 exhibited excellent adsorption capacity over a wide range of pH values and cetyl/amino-SBA 15(3.2/0.8) displayed the highest adsorption capacity up to 120 mg g(-1). Furthermore, cetyl/amino-SBA-15 exhibited high adsorption selectivity for 4-NP against phenol as well as high reusability, showing great potential for applications in wastewater treatment. PMID- 26146030 TI - [Abnormal neurological manifestations in a 44-year-old man]. PMID- 26146032 TI - Demonstration of polarization-insensitive spatial light modulation using a single polarization-sensitive spatial light modulator. AB - We present a simple configuration incorporating a single polarization-sensitive phase-only liquid crystal spatial light modulator (LC-SLM) to facilitate polarization-insensitive spatial light modulation. The polarization-insensitive configuration is formed by a polarization beam splitter (PBS), a polarization sensitive phase-only LC-SLM, a half-wave plate (HWP), and a mirror in a loop structure. We experimentally demonstrate polarization-insensitive spatial light modulations for incident linearly polarized beams with different polarization states and polarization-multiplexed beams. Polarization-insensitive spatial light modulations generating orbital angular momentum (OAM) beams are demonstrated in the experiment. The designed polarization-insensitive configuration may find promising applications in spatial light modulations accommodating diverse incident polarizations. PMID- 26146031 TI - The homeostatic regulation of REM sleep: A role for localized expression of brain derived neurotrophic factor in the brainstem. AB - Homeostatic regulation of REM sleep plays a key role in neural plasticity and deficits in this process are implicated in the development of many neuropsychiatric disorders. Little is known, however, about the molecular mechanisms that underlie this homeostatic regulation process. This study examined the hypothesis that, during selective REM sleep deprivation (RSD), increased brain-derived neurotrophic factor (BDNF) expression in REM sleep regulating areas is critical for the development of homeostatic drive for REM sleep, as measured by an increase in the number of REM sleep transitions. Rats were assigned to RSD, non-sleep deprived (BSL), or total sleep deprivation (TSD) groups. Physiological recordings were obtained from cortical, hippocampal, and pontine EEG electrodes over a 6h period, in which sleep deprivation occurred during the first 3h. In the RSD, but not the other conditions, homeostatic drive for REM sleep increased progressively. BDNF protein expression was significantly greater in the pedunculopontine tegmentum (PPT) and subcoeruleus nucleus (SubCD) in the RSD as compared to the TSD and BSL groups, areas that regulate REM sleep, but not in the medial preoptic area, which regulates non-REM sleep. There was a significant positive correlation between RSD-induced increases in number of REM sleep episodes and increased BDNF expression in the PPT and SubCD. These increases positively correlated with levels of homeostatic drive for REM sleep. These results, for the first time, suggest that selective RSD-induced increased expression of BDNF in the PPT and SubCD are determinant factors in the development of the homeostatic drive for REM sleep. PMID- 26146033 TI - The impact of hemodialysis on cognitive dysfunction in patients with end-stage renal disease: a resting-state functional MRI study. AB - To investigate the effect of hemodialysis (HD) on cognitive dysfunction in patients with end-stage renal disease (ESRD) using resting-state functional MR imaging (rs-fMRI) with regional homogeneity (ReHo) and functional connectivity algorithms. The rs-fMRI data were acquired in 58 ESRD patients (HD patients, n = 32, 22 male and 10 female, mean age 36.5 +/- 9.6 years; non-HD ESRD patients, n = 26, 16 male and 10 female, mean years of 35.6 +/- 8.2) and 32 healthy controls (22 male and 10 female, mean years of 32.7 +/- 8.8). A battery of neuropsychological and blood laboratory tests were prescribed. The Kendall's coefficient of concordance (KCC) was used to measure ReHo for each subject. The ReHo maps were compared by using ANOVA tests among HD, non-HD, and healthy control groups. Regions showing ReHo differences between HD and non-HD patients were defined as seeds for further functional connectivity analysis. A multiple regression analysis was performed to evaluate the relationships between ReHo index and neuropsychological tests, serum creatinine and urea levels, disease and dialysis duration. Compared with healthy controls, both HD patients and non-HD patients showed decreased ReHo in the multiple areas of bilateral frontal, parietal and temporal lobes. Compared with the non-HD, HD patients showed decreased ReHo mainly in default mode network (DMN) including bilateral precuneus, posterior cingulate cortex, inferior parietal lobe, right postcentral gyrus, bilateral superior temporal gyri, right supramarginal gyrus and right angular gyrus. Some reduced ReHo brain regions correlated with some neuropsychological tests, serum creatinine and urea levels, and dialysis duration. Brain regions with ReHo reduction showed increased region-to-region functional network in HD patients compared with non-HD patients. Widespreadly decreased ReHo values were found in both HD and non-HD patients. Lower ReHo values mainly in the DMN correlated with cognition impairments were observed in HD patients compared with non-HD patients, while increased functional connectivity was found between these brain regions. HD might have an adverse effect on the cognitive function in ESRD patients. PMID- 26146034 TI - [Update on the medical treatment of lower urinary tract symptoms (LUTS) in men]. AB - Lower urinary tract symptoms (LUTS) are a frequent cause of consultation in Primary Care, especially in men >40 years of age. Benign prostatic hyperplasia (BPH) has been recognized as the most common cause of bothersome LUTS, causing significant interference with everyday activities and quality of life. The purpose of this study is to provide an update on recent developments regarding the medical management of male LUTS. PMID- 26146035 TI - [Therapeutic equivalence of the new oral anticoagulants]. AB - In an attempt to minimize the economic impact due to the incorporation of innovative drugs, health authorities have promoted and supported the evaluation and market positioning of drugs, as equivalent therapeutic alternatives. This issue has recently gained importance, possibly due to the current economic crisis. The equivalent therapeutic alternatives are justified by the need to compete on price, and by the authorities recommendation to establish therapeutic equivalence, price and financing of medicinal products at the same time. The establishment of the new oral anticoagulants and the equivalent therapeutic alternatives is a problematic issue if it is based on the absence of direct comparisons between different drugs and the questionable methodology used in the current indirect comparisons. Currently, it is difficult to determine when a new oral anticoagulant is more recommendable than others, but efforts are being made in order to propose alternatives for the decision based on patient characteristics. PMID- 26146036 TI - [Heterotopic pregnancy: A rare cause of acute abdomen]. PMID- 26146037 TI - [Syringoma]. PMID- 26146038 TI - [Scombroid: Frequent cause of food poisoning]. PMID- 26146039 TI - Effect of African leafy vegetables on the micronutrient status of mildly deficient farm-school children in South Africa: a randomized controlled study. AB - OBJECTIVE: A randomized controlled trial was conducted to assess the effect of African leafy vegetable (ALV) consumption on Fe, Zn and vitamin A status in children. DESIGN: Children were randomly allocated to receive either a 300 g cooked ALV dish and school meal starch (n 86) or the normal school meal (n 81) five times per week for three months. ALV in the dish consisted mainly of Amaranthus cruentus (at least 80 %) and the remainder of Cleome gynandra, Cucurbita maxima or Vigna unguiculata. Nutrient content and consumer acceptance of the ALV dish were also determined. SETTING: North West Province, South Africa. SUBJECTS: Grade R to grade 4 children (6-12 years old) of two farm schools. RESULTS: The ALV dish contributed 11.6-15.8 mg Fe and 1.4-3.7 mg Zn. At baseline, prevalence of deficiencies in the intervention group was 16.0 %, 16.3 %, 7.0 % and 75.6 %, respectively, for anaemia (Hb<11.5 g/dl), Fe (serum ferritin<15 ug/l), vitamin A (serum retinol<20 MUg/dl) and Zn (serum Zn<65 MUg/dl); and in the control group 10.5 %, 18.5 %, 2.5 % and 75.3 %, respectively. No significant estimated intervention effect was found. CONCLUSIONS: This randomized controlled trial showed that ALV were unable to improve serum retinol, serum ferritin or Hb if there are only mild deficiencies present. Furthermore, despite the low Zn status in the study population, ALV consumption did not improve serum Zn concentrations either. PMID- 26146040 TI - [Molecular methods in diagnosis of poorly differentiated malignant brain tumors in children]. AB - The histological diagnosis of malignant brain tumors in children is a complex process. In some cases, glioblastoma, primitive neuroectodermal tumor of the central nervous system, and atypical teratoid/rhabdoid tumor have a histological type similar to that of small blue round cell malignant tumor. Despite the similar histology, biological properties and approaches to treatment, these neoplasms are completely different and require their own treatment protocols. We retrospectively reviewed the most malignant types of childhood tumors and analyzed our own experience to propose a diagnostic algorithm for intracerebral small blue round cell malignant tumors in children based on the use of immunohistochemistry and fluorescence in situ hybridization. PMID- 26146041 TI - [The effect of gene therapy with the APOE3 Gene on structural and functional manifestations of secondary hippocampal damages in experimental traumatic brain injury]. AB - AIM OF THE STUDY: to study the efficiency of gene therapy following traumatic brain injury (TBI) by evaluating the influences of liposomal transfection of the brain tissue by APOE3-containing plasmid vector on the structural and functional manifestations of development of secondary brain injuries after acute experimental TBI in the rats of different age. MATERIAL AND METHODS: Severe diffuse TBI in rats was inflicted under overall anesthesia by free load weighing 450 g, falling from a 1.5 m elevation. The mixture of DOTAP liposome and 25 MUg of plasmid vector pCMV.SPORT6 with cDNA of APOE3 gene was infused intraventricularly using ALZET osmotic pumps. Combined morphological, electron microscopic, immunohistochemical and morphometric studies of SA1 hippocampal region were conducted in rats at days 5 and 10 following TBI and gene therapy after investigation of motor functions (using composite neurological motor score) and cognitive functions in Morris water maze. RESULTS: Significant changes in the morphofunctional state of hippocampus, as well as in the neurological and cognitive functions were shown on the model of severe TBI in the adult and old Wistar rats. Gene therapy, specifically cationic-liposome mediated APOE3 gene transfer to the CNS cells by plasmid vector, decreased a TBI-induced death of neurons and improved qualitative composition of neuronal population, normalized neuron-glial relations, decreased gliosis and microglial activation, axonal damage, myelin destruction and lipofuscin accumulation, all these having age related peculiarities. After gene therapy observed in the animal brain was a lower intensity of the processes of apoptosis and a decrease of its rate in old animals. The above changes were accompanied with a more fast and expressed regress of neurological and cognitive disturbances typical for TBI. Administration of plasmid vector after TBI resulted in an increase of survival rate of old animals vs. old animals which got no gene therapy. CONCLUSION: APOE3 gene therapy has therapeutic potential in the treatment of severe TBI. PMID- 26146042 TI - [Glioblastoma metastases: a literature review and a description of six clinical observations]. AB - INTRODUCTION: since the 1990s, the literature has described cases of glioblastoma metastases with the development of foci located at a distance from the primary tumor. However, the pathogenesis of this process remains unclear until the end. This focus is believed to result, on the one hand, from tumor metastasis from the primary site and, on the other hand, from multifocal growth. This article presents a literature review and a description of clinical observations of patients with glioblastoma metastases. MATERIAL AND METHODS: The study included 6 patients (1 female and 5 males) with brain glioblastomas who received treatment at the Burdenko Neurosurgical Institute (5 patients) and the Department of Neurosurgery of the Research Center of Neurology (1 patient) in the period from 2010 to 2014. Neurophysiological control was used if the tumor was localized near the eloquent cortical areas and pathways; 4 of 6 patients were operated on using the methods of intraoperative fluorescence diagnosis (5-ALA agent--Alasens). RESULTS: Four patients had metastases within one hemisphere, two had metastases in the contralateral hemisphere in the period of 5 to 18 months after the first operation. The primary tumor site was located near the ventricular system in two patients. In one patient, the lateral ventricle was opened during the first operation. In another patient, the prepontine cistern was opened during the first operation. In two patients, the primary tumor site was located at a distance from the lateral ventricles, however, the tumor was located near them during recurrence. Based on metabolic navigation, fluorescence of the tumor was observed in the four patients during both the first and repeated operations. CONCLUSIONS: The close relationship between primary glioblastomas and metastases and the cerebrospinal fluid circulation pathways may confirm the fact of dissemination of tumor cells with cerebrospinal fluid flow. In our opinion, there should be an increased suspicion of the possibility for metastases of glioblastomas that are closely associated with the cerebrospinal fluid circulation pathways. Metabolic navigation with 5-ALA is effective both during primary surgery in patients with glioblastomas and during resection of glioblastoma metastases. PMID- 26146043 TI - [Life quality of patients with benign tumors of the anterior and middle part of the skull base after surgery and during follow-up]. AB - The results of surgical and combination therapy of 302 patients with benign tumors of the anterior and middle regions of the skull base with allowance for the functional outcomes (immediately after surgery and during the catamnestic follow-up) are reported. The Karnofsky and Rankin scales and the Anterior Skull Base Questionnaire (ASBQ) were used for the analysis. Radical tumor resection, as compared to partial resection, reduces the quality of life in the early postoperative period but increases it in future; the use of radiation therapy in combination treatment for patients with radically inoperable tumors does not worsen their quality of life in the late postoperative period. PMID- 26146044 TI - [Clinical diagnostic features of surgical treatment for thoracic outlet syndrome]. AB - The thoracic outlet syndrome is characterized by a variety of clinical signs due to multiple causes resulting in compression of a neurovascular bundle in a relatively narrow anatomical space. Despite the frequently encountered clinical symptoms, inadequate attention is paid to their analysis, and their diagnostic and surgical aspects require a modern approach. The study included 46 patients. The main clinical sign is a persistent pain syndrome of the cervico-occipital localization that affects the shoulder girdle, suprascapular and infrascapular regions and spreads to the arm in combination with trophic, sensory and vascular disorders. SCT angiography of the superior thoracic outlet structures has been used as a priority instrumental method of research. The macro- and micro factors of compression are the main cause for the development of neurological symptoms, and their removal is the main task of surgical treatment. Surgical approaches were planned depending on the nature and extent of injury. 36 patients underwent 42 surgical interventions. The proper assessment of the neurological status in combination with modern paraclinical diagnostic methods and selection of an adequate surgical approach provided satisfactory outcomes in 33 cases. PMID- 26146045 TI - [Experience of using neuroendoscopy in treatment of noncommunicating hydrocephalus in infants]. AB - 320 children were operated on for occlusive hydrocephalus for 10 years (2003 2012). Infant patients amounted to 93.4%, of these newborns were 29.2%. An endoscopic technique was used to restore physiological liquor circulation and compensate for hydrocephalus without shunt implantation. The positive outcome was observed in 75% of cases. Occlusion of the subarachnoid space occurred in the other cases, which required a combination of neuroendoscopic intervention and shunt implantation. There were no complications and mortality associated with an operative trauma. PMID- 26146046 TI - [De novo cerebral aneurysms]. AB - OBJECTIVE: To substantiate the reasonability and duration of angiographic follow up of patients operated on for cerebral aneurysms to rule out de novo aneurysm formation. MATERIAL AND METHODS: The results of angiographic examination (cerebral angiography and SCT angiography) of 43 patients with cerebral aneurysms operated on at the Burdenko Neurosurgical Institute in 1995-2012 are analyzed. The follow-up duration varied from 1 to 14 years after surgery (mean duration, 5 years). Patients' age ranged from 14 to 56 years. RESULTS: Control angiographic examination showed that de novo aneurysms were formed in 7 (16.2%) patients. A total of 8 de novo aneurysms were detected (in one case there were two aneurysms formed). All aneurysms, both the previously operated and the de novo ones, were located in the anterior part of the circle of Willis. De novo aneurysms were clipped in 5 cases; the cavity of the de novo aneurysm was occluded with spirals in one case. One patient with a small aneurysm of the middle cerebral artery refused surgery. Neither lethal nor unfavorable outcomes were recorded. CONCLUSIONS: The patient groups with the high risk of de novo aneurysm formation are as follows: 1) young smokers with hypertension; 2) patients who developed clinical signs of the disease when being young; 3) patients subjected to proximal exclusion of the main artery; and 4) patients with multiple and familial forms of the pathology. Dynamic angiographic follow-up (SCT angiography or magnetic resonance angiography) for 1-3 years is recommended for these patients. PMID- 26146047 TI - [The effectiveness of using HyperHAES hypertonic isooncotic plasma solution to achieve stable intracranial hypotension in endoscopic endonasal transsphenoidal adenomectomy as an alternative to the invasive external lumbar drainage]. AB - The structure of surgery of pituitary adenomas has been fundamentally changed over the past decade. The transnasal transsphenoidal approach is currently used to resect more than 95% of adenomas. The wide use of endoscopy has changed the need for perioperative control of intracranial pressure. While controlled intracranial hypertension was previously used during microscopically controlled transnasal surgery to bring the suprasellar capsule and tumor remnants to the field of vision, endoscopically controlled tumor resection implies that controlled intracranial hypotension is required to achieve complete spreading of the suprasellar capsule. External lumbar drains inserted at least for the entire surgery duration are conventionally used to control intracranial pressure. We present the results of the study proving the effectiveness and safety of the HyperHAES hypertonic isooncotic plasma substitute in achieving stable intracranial hypotension according to a large body of clinical data. Our findings give grounds for claiming that the use of the HyperHAES hypertonic isooncotic plasma substitute during the standard adenomectomy allows one to abandon the use of invasive external lumbar drainage, while the surgery quality and risks remain at the same level. PMID- 26146048 TI - [Multiple primary liponeurocytoma of the central nervous system]. AB - We report a unique case of primary multiple liponeurocytoma. Liponeurocytoma is a rare benign tumor (Grade II) of the posterior cranial fossa with neural- or probably astrocytic-lineage cells; the tumor stroma contains mature adipocytes. This case is the thirty-eighth case of this pathology reported in the world literature and the first case of multiple form of this disease. We have provided a sufficiently thorough neuroradiological and histological picture that allows one to differentiate between a liponeurocytoma and other histological variants. Recommendations for the tactics for managing patients with this rare disease are proposed based on the analysis of treatment of this pathology reported in the world literature. PMID- 26146049 TI - [An advisory protocol for treatment of acute complicated and uncomplicated spinal cord injury in adults (association of neurosurgeons of the Russian Federation). Part 3]. PMID- 26146050 TI - Insights from an international stakeholder consultation to identify informational needs related to seafood safety. AB - Food safety assessment and communication have a strong importance in reducing human health risks related to food consumption. The research carried out within the ECsafeSEAFOOD project aims to assess seafood safety issues, mainly related to non-regulated priority environmental contaminants, and to evaluate their impact on public health. In order to make the research results accessible and exploitable, and to respond to actual stakeholders' demands, a consultation with international stakeholders was performed by means of a survey. The focus was on policy and decision makers, food producers and processors, and agencies (i.e. EU and National or Regional agencies related to Food Safety or Public Health) and consumer organisations. The survey considered questions related to: seafood safety assessment and mitigation strategies, availability of data, such as the level of information on different contaminants, and communication among different stakeholder groups. Furthermore, stakeholders were asked to give their opinion on how they believe consumers perceive risks associated with environmental contaminants. The survey was distributed to 531 key stakeholders and 91 responses were received from stakeholders from 30 EU and non-EU countries. The main results show that communication between different groups of stakeholders needs to be improved and that there is a deficit of information and data in the field of seafood safety. This pertains mainly to the transfer of contaminants between the environment and seafood, and to the diversity of environmental contaminants such as plastic additives, algal toxins and hormones. On-line tools were perceived to be the most useful communication channel. PMID- 26146051 TI - [Effects of lipopolysaccharide and phytohaemagglutinin on the level of microRNAs in mouse peripheral blood mononuclear cells]. AB - OBJECTIVE: To investigate the effects of lipopolysaccharide (LPS) and phytohaemagglutinin (PHA) on the level of microRNAs in mouse peripheral blood mononuclear cells (PBMCs). METHODS: The mouse PBMCs were cultured in vitro and stimulated with 100 ng/mL LPS for 1 hour or 2 hours and 2.5 MUg/mL phytohaemagglutinin (PHA) for 2 hours or 4 hours, respectively. The levels of miR 9, miR-122-3p, miR-181d and miR-342-3p in both PBMCs and culture supernatants were determined by real-time quantitative PCR (qRT-PCR). RESULTS: The levels of miR-9, miR-122-3p, miR-181d and miR-342-3p in PBMCs and culture supernatants had no significant difference between blank control and LPS stimulation group, nor did between LPS stimulation 2 hours group and 1 hour group. The levels of miR-9, miR-122-3p and miR-342-3p in PBMCs and culture supernatant had no significant difference between blank control and PHA stimulation group, nor did between PHA stimulation 4 hours group and 2 hours group. However, compared with blank control, the expression of miR-181d significantly increased after PHA stimulation, while the time of stimulation did not affect the miR-181d level significantly. CONCLUSION: The stimulation of PHA could promote the expression and secretion of miR-181d in mouse PBMCs. PMID- 26146052 TI - [Tumor necrosis factor alpha enhances apoptosis of all-trans retinoic acid induced promyelocytic leukemia cells]. AB - OBJECTIVE: To study the effect of tumor necrosis factor alpha (TNF-alpha) on apoptosis of human promyelocytic leukemia cells induced by all-trans retinoic acid (ATRA). METHODS: Human acute promyelocytic leukemia NB4 cells were treated either by ATRA or by ATRA plus TNF-alpha. Cell proliferation and apoptosis were detected by cell counting and annexin V-FITC/PI staining, respectively. Changes of CD11b expression on NB4 cells were observed by flow cytometry. RESULTS: Compared with NB4 cells treated with ATRA alone, NB4 cells treated with ATRA plus TNF-alpha showed slower proliferation and a higher rate of apoptosis during the whole process of differentiation, and had a higher ratio of CD11b positive cells on the second day of differentiation. CONCLUSION: TNF-alpha may have potential for strengthening the differentiation and apoptosis of acute promyelocytic leukemia cells induced by ATRA. PMID- 26146053 TI - [C3H10 T1/2 cells over-expressing CCR7 have intensive immunosuppressive effect]. AB - OBJECTIVE: To evaluate whether the chemokine (C-C motif) receptor 7 (CCR7) over expressing C3H10 T1/2 mesenchymal stem cells are more efficient in immunosuppression effects than the original ones in skin grafts in mice. METHODS: The C3H10 T1/2 cells were amplified and transfered with EGFP-CCR7 gene using lentivirus. The skin grafts were harvested from donators (C57BL/6 mice) and then transplanted to recipients (BALB/c mice). The recipients were divided into 4 groups randomly: CCR7+ C3H10 T1/2 group (1 * 106 CCR7+ C3H10 T1/2 cells suspended in 1 mL PBS were injected into the recipient mice by caudal vein), C3H10 T1/2 group (1 * 106 C3H10 T1/2 cells were injected into the recipient mice after skin graft), allogenic control group (the mice were injected with 1 mL normal saline), and congenic control group (the BALB/c mice that had received the skin from the congenic ones were injected with 1 mL normal saline). The skin graft survival condition and histopathological changes were observed on the 12th postoperative day. The Th17 cells and regulatory T cells (Tregs) in the lymphocytes of spleen were detected by mouse Th17/Treg phenotyping kit. RESULTS: On the 12th postoperative day, the skin surface features, histopathologic changes and flow cytometry results indicated that the skin graft survival condition of the allografts treated with CCR7+ C3H10 T1/2 or C3H10 T1/2 cells were better than that of the allogenic control group. Compared with C3H10 T1/2 cells, CCR7+ C3H10 T1/2 cells had better skin graft survival condition and weaker immune response. CONCLUSION: CCR7+ C3H10 T1/2 cells induce more intensive immunosuppressive effects than original C3H10 T1/2 cells. CCR7+ C3H10 T1/2 cells significantly inhibit inflammatory reaction and improve the living state of skin allograft. PMID- 26146054 TI - [FHL1 knockdown mediated by lentiviral shRNA promotes the growth of HeLa and HepG2 cells]. AB - OBJECTIVE: To investigate the effect of four-and-a-half LIM domain 1 (FHL1) knockdown by lentiviral-mediated shRNA on the growth of HeLa and HepG2 cells. METHODS: pLenti-H1 FHL1 shRNA was cloned, and then transfered into HEK293T cells. The inhibitory effect of pLenti-H1 FHL1 shRNA on FHL1 gene was detected by Western blotting and real-time quantitative PCR (qRT-PCR). Lentivirus particles were packaged, added to HeLa and HepG2 cells, followed by puromycin treatment for 2-3 weeks to screen stable clones. The knockdown effect on FHL1 expression in these cells was checked by Western blotting and qRT-PCR. Cell growth and colony formation analysis were performed to investigate the effect of FHL1 down regulation on tumor cell growth. Soft agar analysis was used to analyze its effect on anchorage-independent tumor cell growth. RESULTS: Western blotting and qRT-PCR revealed that the pLenti-H1 FHL1 shRNA apparently inhibited the expression of FHL1 gene. Cell growth and colony formation assay showed that the lentiviral-mediated shRNA for FHL1 gene significantly accelerated the tumor cell growth in HepG2 and HeLa cells. Soft agar analysis demonstrated that FHL1 shRNA increased the anchorage-independent growth of tumor cells. CONCLUSION: pLenti-H1 FHL1 shRNA could significantly accelerate tumor cell growth via inhibiting the expression of FHL1. PMID- 26146055 TI - [Over-expression of transcription factor 21 inhibits the proliferation and migration and promotes apoptosis of SMMC-7721 cells]. AB - OBJECTIVE: To explore the impact of transcription factor 21 (TCF21) gene on proliferation, migration and apoptosis in SMMC-7721 hepatocellular carcinoma cell line and the related mechanism. METHODS: Using LipofectamineTM2000, we stably transfected pcDNA3.1+TCF21 and pcDNA3.1+ plasmids into SMMC-7721 cells of TCF21 over-expression group and empty vector group, respectively. The untreated cells were set as blank control group. The expression of TCF21 mRNA and protein were investigated by reverse transcription PCR and Western blotting. Cell proliferation ability was detected by MTT assay. Wound healing assay was used to observe cell migration ability. Annexin V-FITC/PI double labeling combined with flow cytometry was applied to determine cell apoptosis rate. Western blotting was performed to examine the expressions of KISS1, P53 and matrix metalloproteinase-9 (MMP-9). RESULTS: TCF21 was over-expressed in TCF21-transfected SMMC-7721 cells. Compared with the control groups, the TCF21 over-expression group showed relatively weakened proliferation ability and significantly inhibited migration ability as well as the increased apoptosis. Western blotting demonstrated that up regulated TCF21 raised the expressions of KISS1 and p53, and down-regulated MMP-9 level. CONCLUSION: Tumor-suppressor gene TCF21 could inhibit the proliferation and migration of SMMC-7721 hepatocellular carcinoma cells and promote its apoptosis. PMID- 26146056 TI - [Resveratrol inhibits cell proliferation and up-regulates MICA/B expression in human colon cancer stem cells]. AB - OBJECTIVE: To investigate the effect of resveratrol (Res) on the proliferation, apoptosis and immunogenicity of colorectal cancer stem cells (CCSCs). METHODS: The CCSCs were induced from colon cancer cell line HCT116 in serum-free medium (SFM). The expressions of CD133 and CD44 were detected by flow cytometry to identify CCSCs. After treatment with Res at (12.5-200.0) MUmol/L, the effect of Res on CCSC proliferation was detected by MTT assay ; cell apoptosis was examined by flow cytometry combined with annexin V-FITC/PI staining; cell cycle and the expression of major histocompatibility complex class I-related chain A and B (MICA/B) were assessed by flow cytometry. RESULTS: HCT116 cells formed cancer stem cell spheres in SFM. The proportion of CD133+ cells in cell spheres was (91.07 +/- 1.79)%, and CD44+ cells was (90.33 +/- 1.78)%. Compared with control groups, Res significantly inhibited CCSC proliferation in a time- and dose depended manner. After treatment with Res for 48 hours, the proportion of cells increased in the G0/G1 phase and decreased in the S phase, both in a dose depended manner. Apoptosis rate of CCSCs and the expression of MICA/B were raised with the increasing concentration of Res. CONCLUSION: CCSCs were successfully induced from HCT116 colon cancer cell line. Res could depress CCSC proliferation in a time-and dose-depended manner, arrest cell cycle in the G0/G1 phase and promote cell apoptosis. Res could up-regulate the expression of MICA/B in CCSCs and enhance cell immunogenicity. PMID- 26146058 TI - [ASPP2 inhibits oxaliplatin-induced autophagy and promotes apoptosis of colon cancer cells]. AB - OBJECTIVE: To investigate the role of apoptosis stimulating p53 binding protein 2 (ASPP2)-induced p53-dependent and p53-independent autophagy inhibition in apoptosis-promoting function of oxaliplatin (OXA). METHODS: According to different treatments, HCT116(p53(-/-)) cells were divided into 6 groups: rapamycin combined with ASPP2 group, ASPP2 group, p53 group, ASPP2 combined with p53 group, OXA combined with 3-methyladenine (3-MA) group, control group (OXA treatment or starvation without OXA treatment). When the level of apoptosis was detected, green fluorescent protein-advirus (GFP-Ad) group and rapamycin group were supplemented as controls. Cells were transfected with GFP-microtubule associated protein 1 light chain 3 (GFP-LC3) plasmid, and LC3-expressing cells were calculated under a fluorescent microscope. Expressions of autophagy-related molecules were detected by Western blotting. Cells were subjected to annexin V FITC/PI staining and apoptosis was assessed by flow cytometry. RESULTS: The 3-MA group showed the same inhibitory ability on autophagy with the ASPP2 group, and both of them were able to promote OXA or starvation-induced apoptosis, but the cell apoptosis rate in the 3-MA group was lower than that of the ASPP2 group. Rapamycin combined with ASPP2 still promoted OXA or starvation-induced apoptosis, and the apoptosis rate was also lower than that of the ASPP2 group. However, rapamycin counteracted effectively the inhibitory effect of ASPP2 on autophagy. CONCLUSION: OXA can induce autophagy of colorectal cancer cells, while ASPP2 over expression can suppress the OXA-induced autophagy. ASPP2 can promote apoptosis through p53-dependent and p53-independent pathways. The function of ASPP2 promoting cell apoptosis through p53-dependent and p53-independent pathways is not entirely achieved by inhibiting cell autophagy. PMID- 26146057 TI - [Effects of Yiqiyangyin recipe on the mRNA levels of TNF-alpha, TGF-beta1 and IFN gamma of lungs in rats with pulmonary interstitial fibrosis]. AB - OBJECTIVE: To investigate the effects of Yiqiyangyin recipe on lung tissue morphological structure and mRNA levels of tumor necrosis factor alpha (TNF alpha), transforming growth factor beta-1 (TGF-beta1) and interferon-gamma (IFN gamma) in pulmonary interstitial fibrosis rat models. METHODS: The pulmonary interstitial fibrosis rat model was established by intrabronchial injection of bleomycin A5. After the model was set up, the rats were divided randomly into five groups, normal group, model group, prednisone acetate group, traditional Chinese medicine (TCM) group, and TCM plus prednisone acetate group. Twenty-eight days after modeling, all groups were subjected to gavage for another 28 days. Then the animals were executed in batch. Their lung tissues were separated and observed with HE staining and Masson staining. The mRNA levels of TNF-alpha, TGF beta1 and IFN-gamma were detected using in situ hybridization. RESULTS: The levels of TNF-alpha and TGF-beta1 mRNAs were enhanced and IFN-gamma mRNA was weakened in the model group as compared with the other groups at the same time points. Compared with the prednisone acetate group and the TCM plus prednisone acetate group, the expression of TNF-alpha mRNA was reduced and IFN-gamma mRNA was raised a little in the TCM group at the same time points. Compared with the prednisone acetate group at the same time points, the level of TGF-beta1 mRNA decreased slightly in the TCM group. CONCLUSION: Yiqiyangyin recipe could delay pulmonary fibrosis by reducing the mRNA levels of TNF-alpha and TGF-beta1 and increasing IFN-gamma mRNA in lung tissues of pulmonary intestitial fibrosis rats. PMID- 26146059 TI - [Up-regulation of molecules associated with Sonic hedgehog signaling pathway plays a protective role in mouse acute lung injury induced by lipopolysaccharide]. AB - OBJECTIVE: To explore the expression changes and significance of Sonic hedgehog (SHH) signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: The experimental animals were randomly divided into control group, LPS-treated group (LPS 5 mg/kg) and cyclopamine-treated group (cyclopamine 50 mg/kg). The pathological changes of lung tissues were observed with HE staining, and the lung wet to dry mass ratio (W/D) was measured. Real-time quantitative PCR (RT-PCR) was used to detect the mRNA expressions of tumor necrosis factor alpha (TNF-alpha), SHH, Patched (PTC) and downstream transcription factor GLI1 in lung tissues, and Western blotting was adopted to determine the protein levels of SHH and GLI1 in lung tissues. RESULTS: Pathological injury score of lung tissues, W/D and mRNA level of TNF-alpha were significantly higher in the LPS-treated group than in the control group. Compared with the control group, the mRNA levels of SHH, PTC and GLI1 in the LPS-treated group were not significantly different at 6 hours and were remarkably higher at 12 and 24 hours, with a positive correlation with the time. Protein expression levels of SHH and GLI1 at 6, 12 and 24 hours in the LPS-treated group showed a more notable increase than those in the control group, and a positive correlation with the time was displayed. After cyclopamine intervention, the mRNA levels of SHH, PTC and GLI1 and the protein levels of SHH and GLI1 were all reduced, while pathological injury score of lung tissues, W/D and mRNA level of TNF-alpha were obviously higher than those in the LPS-treated group. CONCLUSION: SHH signaling pathway was activated in the development process of LPS-induced ALI, and up regulated expressions of SHH signaling pathway associated molecules could relieve lung injury and involve repair of the injured lung tissues. PMID- 26146060 TI - [Astragalus polysaccharides combined with cisplatin decreases the serum levels of CD44 and collagen type IV and hyaluronic acid in mice bearing Lewis lung cancer]. AB - OBJECTIVE: To observe the effects of Astragalus polysaccharides (APS) combined with cisplatin on growth of Lewis lung cancer (LLC), serum content of collagen type IV (Col4) and hyaluronic acid (HA), and CD44 protein level in LLC-bearing mice. METHODS: C57BL/6J mice (n=90) were randomly divided into 2 groups, 10 mice for blank control group, and 80 mice for tumor-bearing group. The tumor-bearing group was then randomized into 8 subgroups, 10 mice for each subgroup. The tumor bearing mice were treated by peritoneal injection of normal saline, 6 mg/kg cisplatin, 50, 100, 200 mg/kg APS, and 3 mg/kg cisplatin combined with 50, 100, 200 mg/kg APS, respectively. APS (0.3 mL) was injected once a day from the first to the 20th day after LLC transplantation, and cisplatin of the same volume was injected once a week. On the 21st day, the blood was taken from the eyeballs of all experimental mice. Col4 and HA contents in serum were detected by radioimmunoassay. The expression of CD44 in transplanted tumor cells was determined by immunohistochemistry and image analysis. The inhibition rate of tumor growth was also counted. RESULTS: The inhibition rates of 6 mg/kg cisplatin, 50, 100, 200 mg/kg APS, and 3 mg/kg cisplatin combined with 50, 100, 200 mg/kg APS on LLC growth in the mice were 49.30%, 17.21%, 39.68%, 42.98%, 51.02%, 57.21% and 65.11%, respectively. Compared with the control subgroup of the tumor-bearing group, cisplatin, APS and cisplatin combined with APS reduced significantly the Col4 and HA content in serum, and down-regulated the expression of CD44. CONCLUSION: APS can inhibit the growth of LLC cells, reduce the Col4 and HA content in serum, down-regulate the expression of CD44 protein in LLC-bearing mice, and enhance the therapeutic effect when combined with cisplatin, indicating that it can decrease the toxicity of cisplatin against tumor. PMID- 26146061 TI - [The fragments of dead macrophages infected by Brucellasuis S2 strain activates the immune response against Brucella infection]. AB - OBJECTIVE: To investigate the role of the dead macrophages infected by Brucella suis S2 strain in the initiation of immune response to Brucella. METHODS: The mouse peritoneal macrophages were infected with Brucella suis S2 strain in vitro. After one hour, the cells were cultured in serum-free RPMI1640 medium for 5 days until all of them were dead because of starvation. The dead cell fragments and the bone marrow-derived dendritic cells (BMDCs) were co-cultured for 24, 48 and 72 hours, and then interleukin 12 (IL-12), tumor necrosis factor alpha (TNF alpha) in the co-cultivation supernatant were detected by ELISA. The mouse macrophages marked by carboxyfluorescein diacetate succinimidyl ester (CFSE) were infected with Brucella suis S2 strain in vitro, and then were cultured without serum in the dark; the dead macrophages fragments and BMDCs labeled with anti CD11c-PE were co-cultured for 1 hour away from light, and then the changes that BMDCs swallowed the fragments of macrophages were observed by laser scanning confocal microscopy. BALB/c mice were inoculated with the fragments of dead macrophages infected by S2 strain through abdominal cavity. After one week, a second immunization was done. The serum levels of IL-4, IL-2 and IFN-gamma were detected with ELISA at 3 days post-secondary immunization. RESULTS: The macrophages fragments infected by S2 strain could be swallowed by DCs. The level of TNF-alpha in BMDCs swallowing macrophages fragments infected by S2 strain was significantly higher than that in the control group, but the former did not secret IL-12. The levels of IL-2, IL-4 and IFN-gamma in the sera from the mice inoculated with the macrophages fragments infected by S2 strain were dramatically higher than those in the control groups. CONCLUSION: The dead macrophages infected by Brucella suis S2 strain can activate DCs to present antigen and induce the anti-Brucella immune response. PMID- 26146062 TI - [Up-regulation of miR-21 promotes cell proliferation and collagen synthesis in pulmonary fibroblasts]. AB - OBJECTIVE: To explore the expression of miR-21 in lung tissues of mice with pulmonary fibrosis, and its role in proliferation, trans-differentiation and collagen synthesis of pulmonary fibroblasts. METHODS: Thirty C57BL/6 mice were randomly divided into control group (n=5) and model group (n=25). Mice in the latter group were intratracheally administered with bleomycin to establish pulmonary fibrosis model. Five animals in the model group were sacrificed on days 3, 7, 14, 28 and 56, while all ones of the control group were killed on day 56 as total control. The expression of miR-21 in lung tissues was then measured through fluorescence real-time quantitative PCR. Pulmonary fibroblasts were treated with LipofectamineTM2000 (blank control group) as well as miR-21 negative control, mimics and inhibitor, respectively. Cell proliferative ability was analyzed by MTT assay. The mRNA and protein expressions of alpha-smooth muscle actin (alpha SMA), a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1), collagen type I (Col1) and collagen type III (Col3) were detected using fluorescence real-time quantitative PCR and Western blotting, respectively. RESULTS: The expression levels of miR-21 in lung tissues of the model group on days 7-56 were higher than those in the control group, and reached the peak on day 28. After 24, 48, 72 and 96 hours of co-culture, cell viability significantly increased in miR-21 mimics group but decreased in miR-21 inhibitor group as compared with blank control group. In comparison with blank control group, miR-21 mimics group showed up-regulated mRNA and protein expression levels of alpha-SMA, Col1 and Col3 while down-regulated ADAMTS-1 mRNA and protein expression levels; however, miR-21 inhibitor group presented with reduced mRNA and protein expression levels of alpha-SMA, Col1 and Col3 but increased ADAMTS-1 mRNA and protein expression levels. There was no significant difference in the above indicators between negative control group and blank control group. CONCLUSION: miR-21 expression is raised in lung tissues of mice with pulmonary fibrosis. Up regulation of miR-21 facilitates the proliferation, trans-differentiation and collagen synthesis of pulmonary fibroblasts. PMID- 26146063 TI - [The capacity of proliferation and migration is higher in Tca8113 cells with up regulated TNFSF14 expression]. AB - OBJECTIVE: To construct a lentiviral vector carrying tumor necrosis factor superfamily member 14 (TNFSF14) gene, infect tongue cancer Tca8113 cells in vitro, and observe the effect on infected Tca8113 cells. METHODS: A lentiviral vector containing TNFSF14 gene was constructed and used to infect the Tca8113 cells. After selected by puromycin, the level of TNFSF14 mRNA in Tca8113 cells was detected by real-time quantitative PCR. Cell proliferation activity and cell circle were determined respectively by MTT assay and flow cytometry (FCM). And the cell migration ability was measured by Transwell(TM) assay. RESULTS: Compared with the control group, the expression of TNFSF14 mRNA increased in the infected cells. MTT assay and FCM showed TNFSF14 promoted the proliferation of Tca8113 cells. TranswellTM assay showed TNFSF14 boosted the migration ability of Tca8113 cells. CONCLUSION: The proliferation and migration would be enhanced in Tca8113 cells with over-expressed TNFSF14. PMID- 26146064 TI - [Preventive effect of misoprostol against nonsteroidal anti-inflammatory drug induced enteropathy in mice]. AB - OBJECTIVE: To investigate the preventive effect of misoprostol against non steroidal anti-inflammatory drug (NSAID)-induced intestinal injury in mice. METHODS: NSAID-induced intestinal injury model was established through diclofenac sodium. Sixty specific-pathogen-free (SPF) BABL/c male mice were randomly divided into the following five groups: normal, model and three misoprostol groups with different concentrations (200, 400, 800 MUg/kg). Misoprostol was given to aforementioned three misoprostol groups by gavage once a day for 6 days. In the fourth day afternoon, 5 mg/kg (10 mL/kg) diclofenac was fed to all mice by gavage except for normal group. On the seventh day, all mice were sacrificed and intestinal permeability was detected using FITC labeled dextran. The intestinal tissues were taken for detecting the mRNA and protein expressions of intestinal glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and tumor necrosis factor alpha (TNF-alpha) through HE staining, reverse transcription PCR and Western blotting, respectively. RESULTS: Compared with the normal group, intestinal mucosa in the model group was seriously damaged and intestinal permeability significantly increased. The intestinal mucosal villus degeneration, necrosis, shedding, and inflammatory cell infiltration occurred in the model group. Yet, intestinal mucosal injury in different misoprostol groups was less severe. Their intestinal mucosal permeability was improved. The expressions of GRP78 protein and TNF-alpha, CHOP mRNAs on intestine were significantly reduced compared with those of the model group. CONCLUSION: Misoprostol has preventive effect against NSAID-induced intestinal diseases. PMID- 26146065 TI - [Prokaryotic expression and immunological activity of human neutrophil gelatinase associated lipocalin]. AB - OBJECTIVE: To construct a prokaryotic expression vector of human neutrophil gelatinase associated lipocalin (NGAL) and identify the bioactivity of the fusion protein. METHODS: The cDNA of human NGAL obtained from GenBank was linked to a cloning vector to construct the prokaryotic expression vector pCold-NGAL. Then the vector was transformed into E.coli BL21(DE3) plysS. Under the optimal induction condition, the recombinant NGAL (rNGAL) was expressed and purified by Ni Sepharose 6 Fast Flow affinity chromatography. The purity and activity of the rNGAL were respectively identified by SDS-PAGE and Western blotting combined with NGAL reagent (Latex enhanced immunoturbidimetry). RESULTS: Restriction enzyme digestion and nucleotide sequencing proved that the expression vector pCold-NGAL was successfully constructed. Under the optimal induction condition that we determined, the rNGAL was expressed in soluble form in E.coli BL21(DE3) plysS. The relative molecular mass of the rNGAL was 25 000, and its purity was more than 98.0%. Furthermore, Western blotting and immunoturbidimetry indicated that the rNGAL reacted with NGAL mAb specifically. CONCLUSION: Human rNGAL of high purity and bioactivity was successfully constructed in E.coli BL21(DE3) plysS using the expression vector pCold-NGAL. PMID- 26146066 TI - [Down-regulated expression of Blimp-1 mRNA in monocytes from patients with active tuberculosis]. AB - OBJECTIVE: To detect the expression of B lymphocyte-induced maturation protein-1 (Blimp-1) mRNA in monocytes of patients with active tuberculosis and analyze the differences of the expression among the patients, latent tuberculosis infection subjects and healthy controls (HCs). METHODS: Anticoagulated peripheral blood was collected from patients with active tuberculosis, latent tuberculosis infection subjects and HCs. Monocytes were isolated and purified from the peripheral blood. Fluorescence quantitative PCR was used to detect the mRNA level of Blimp-1 in monocytes. After the monocytes from HCs were stimulated with whole cell lysate of H37Rv MTB and peptide pool of ESAT-6/CFP-10, respectively, the level of Blimp-1 mRNA was again detected by fluorescence quantitative PCR. RESULTS: The level of Blimp-1 mRNA in the monocytes from patients with active tuberculosis and latent tuberculosis infection subjects were significantly lower than that from HCs. Compared with the unstimulated monocytes, the level of Blimp-1 mRNA in the monocytes stimulated with whole cell lysate of H37Rv MTB significantly decreased, while the expression of Blimp-1 mRNA in the monocytes stimulated with ESAT-6/CFP 10 was not significantly changed. CONCLUSION: The level of Blimp-1 mRNA in the monocytes from patients with active tuberculosis and latent tuberculosis infection subjects was down-regulated, and the expression of Blimp-1 mRNA in the monocytes from HCs was also suppressed after stimulated with whole cell lysate of MTB. PMID- 26146067 TI - [The elevated levels of plasma chemerin and C-reactive protein in patients with acute coronary syndrome]. AB - OBJECTIVE: To investigate the plasma levels of chemerin and C-reactive protein (CRP) in the patients with acute coronary syndrome. METHODS: The plasma levels of chemerin and CRP were respectively measured by ELISA and immune luminescence sandwich assay in 40 patients with acute myocardial infarction (AMI), 40 patients with unstable angina (UA), 40 patients with stable angina (SA) and 40 control patients. RESULTS: The levels of chemerin and CRP were significantly higher in the AMI and UA groups than in the SA and control groups, and the level of chemerin was significantly higher in the AMI group than in the UA group. The level of chemerin was positively correlated with the level of CRP, fasting glucose and left ventricular end-diastolic diameter, but negatively correlated with left ventricular ejection fraction. CONCLUSION: The plasma levels of chemerin and CRP are elevated in patients with acute coronary syndrome. PMID- 26146068 TI - [Over-expression of CCL21 up-regulates the antigen presentation-related genes of CK8/18 positive thymic epithelial cells in patients with myasthenia gravis]. AB - OBJECTIVE: To identify the distribution of chemokine (C-C motif) ligand 21 (CCL21) in the thymus of patients with myasthenia gravis (MG) and explore the effects of up-regulation of CCL21 on the expressions of antigen presentation related genes in cytokeratin 8/18 (CK8/18) positive thymic epithelial cells (TECs) after transfected with CCL21 genes. METHODS: The expressions and distributions of CK8/18 and CCL21 in the thymus tissue of MG patients were detected by immunohistochemistry. The mRNA levels of CCL21, CCL19 and their receptor chemokine (C-C motif) receptor 7 (CCR7) in the thymus tissue of MG patients were determined by real-time quantitative PCR (qRT-PCR). Primary cultured CK8/18+ TECs were transfected with pCMV-CCL21, and the relative mRNA expressions of function-associated genes (CD80, ICAM-1, CD86, HLA-DR, HLA-A) in CK8/18+ TECs before and after the transfection were investigated by qRT-PCR. RESULTS: Immunohistochemical results showed that the number of CK8/18 positive cells in the hyperplastic thymus tissues of MG patients was significantly more than that in the normal controls, and the protein expression of CCL21 was also much higher in the hyperplastic thymus tissues. The qRT-PCR showed that the expressions of CCL21 and CCR7 mRNA increased significantly in hyperplastic thymus tissues of MG patients compared with those in normal controls, while there was no difference in the expression of CCL19. Furthermore, CK8/18 positive cells were found mainly located in cortico-medullary junction and medulla area. The relative mRNA expression levels of HLA-A, HLA-DR, ICAM and CD80 rose significantly in CK8/18+ TECs after transfected with pCMV-CCL21. CONCLUSION: The over-expression of CCL21 could increased the expressions of antigen presentation-related genes in CK8/18+ TECs in MG patients. PMID- 26146069 TI - [Highly expressed CD147 on CD4+ tumor infiltrating lymphocytes promotes the progress of breast cancer]. AB - OBJECTIVE: To investigate the expression of CD147 in CD4+ tumor infiltrating lymphocytes and explore the clinical significance of CD147 transcripts in breast cancer patients by comparing CD147 level in healthy controls' peripheral blood, breast cancer patients' peripheral blood, lymph nodes and CD4+ tumor infiltrating lymphocytes. METHODS: CD147 expression data were derived by Robust Multi-array Averaging method from three different microarrays, GSE14308, GSE36765 and GSE6532. ANOVA, Kaplan-Meier curve and multivariate Cox proportional hazards model were used for the statistical analysis. RESULTS: The expression of CD147 in Th1, Th2 and Th17 cells was 8-12 times higher than that in Th0 cells in normal C57BL/6J mice. The expression level of CD147 in the CD4+ tumor infiltrating lymphocytes from breast cancer patients was significantly higher than that in the CD4+ lymphocytes from peripheral blood of healthy donors, peripheral blood and axillary lymph nodes of breast cancer patients. High expression of CD147 was significantly associated with an increased risk of relapse in the Kaplan-Meier curve analysis (Log-Rank, P=0.019) and multivariate analysis (hazard ratio=1.764; 95% confidence interval: 1.088-2.859). CONCLUSION: CD147 might promote the progress of breast cancer through up-regulating CD4+ tumor infiltrating lymphocytes and aggravating inflammatory reaction. PMID- 26146070 TI - [Prokaryotic expression and polyclonal antibody preparation of antitoxin higA of Mycobacterium tuberculosis]. AB - OBJECTIVE: To clone higA gene from genome of Mycobacterium tuberculosis, express higA protein in E.coli and prepare polyclonal antibodies against higA protein of Mycobacterium tuberculosis. METHODS: HigA gene was obtained by PCR from the genome of Mycobacterium tuberculosis H37Rv strain and inserted into E.coli plasmid pET-32a+. The recombinant expression vector pET-32a+-higA was then transformed into prokaryotic expression bacterium E.coli BL21, and the recombinant protein higA was expressed in E.coli BL21 under IPTG induction. The protein was identified by SDS-PAGE and Western blotting. Purified protein higA was used to immunize New Zealand rabbits to prepare anti-higA polyclonal antibody. Quality and quantity of the antibody were examined. RESULTS: HigA gene was successfully amplified and inserted into pET-32a.+ DNA sequencing confirmed the positive recombinant plasmid pET-32a+-higA screened by PCR and restriction enzyme digestion analysis. After induction with IPTG, the recombinant protein higA with 36.63 kDa was successfully expressed in E.coli BL21. Rabbit anti-higA polyclonal antibody with a good specificity was obtained, and the titer was above 1:3200. CONCLUSION: The higA protein was successfully expressed in E.coli BL21. Rabbit anti-higA antibody with high titer and specificity was prepared. PMID- 26146071 TI - [Preparation and identification of DNA G-quadruplex antibody]. AB - OBJECTIVE: To construct a prokaryotic expression plasmid of DNA G-quadruplex antibody, express it in E.coli BL21 (DE3) bacterial expression system, purify and identify the antibody. METHODS: Chemically synthesized BG4 gene of DNA G quadruplex antibodies was inserted into pSANG10 plasmid to construct DNA G quadruplex antibody expression vector pSANG10-BG4. BL21 (DE3) as the host strain was utilized for self-induced expression of the protein. Osmotic lysis method was used for collecting this protein. Thereafter, the protein was purified by histidine tag affinity chromatography and identified by SDS-PAGE and Western blotting. The function of this protein was verified in SW480 colon cancer cells. RESULTS: Double enzyme digestion and gene sequencing confirmed that DNA G quadruplex antibody expression vector was successfully constructed. The relative molecular mass (Mr) of this protein was 30 000 to 37 000. The protein in a soluble form was expressed in the periplasm of BL21. The protein was of the same size as expected. CONCLUSION: The DNA G-quadruplex antibody has been successfully prepared. PMID- 26146072 TI - Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction. AB - Actin filament organization and stability in the sarcomeres of muscle cells are critical for force generation. Here we identify and functionally characterize a Caenorhabditis elegans drebrin-like protein DBN-1 as a novel constituent of the muscle contraction machinery. In vitro, DBN-1 exhibits actin filament binding and bundling activity. In vivo, DBN-1 is expressed in body wall muscles of C. elegans. During the muscle contraction cycle, DBN-1 alternates location between myosin- and actin-rich regions of the sarcomere. In contracted muscle, DBN-1 is accumulated at I-bands where it likely regulates proper spacing of alpha-actinin and tropomyosin and protects actin filaments from the interaction with ADF/cofilin. DBN-1 loss of function results in the partial depolymerization of F actin during muscle contraction. Taken together, our data show that DBN-1 organizes the muscle contractile apparatus maintaining the spatial relationship between actin-binding proteins such as alpha-actinin, tropomyosin and ADF/cofilin and possibly strengthening actin filaments by bundling. PMID- 26146073 TI - Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma. AB - As the list of putative driver mutations in glioma grows, we are just beginning to elucidate the effects of dysregulated developmental signaling pathways on the transformation of neural cells. We have employed a postnatal, mosaic, autochthonous glioma model that captures the first hours and days of gliomagenesis in more resolution than conventional genetically engineered mouse models of cancer. We provide evidence that disruption of the Nf1-Ras pathway in the ventricular zone at multiple signaling nodes uniformly results in rapid neural stem cell depletion, progenitor hyperproliferation, and gliogenic lineage restriction. Abolishing Ets subfamily activity, which is upregulated downstream of Ras, rescues these phenotypes and blocks glioma initiation. Thus, the Nf1-Ras Ets axis might be one of the select molecular pathways that are perturbed for initiation and maintenance in glioma. PMID- 26146074 TI - Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging. AB - Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR) cells to stimulatory T follicular helper (TFH) cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defective antigen-specific responses, and programmed cell death protein-ligand 1 blockade can partially rescue TFH cell function. In contrast, young and aged TFR cells have similar suppressive capacity on a per-cell basis in vitro and in vivo. Together, these studies reveal mechanisms contributing to defective humoral immunity in aging: an increase in suppressive TFR cells combined with impaired function of aged TFH cells results in reduced T-cell-dependent antibody responses in aged mice. PMID- 26146075 TI - Sensory-Evoked Intrinsic Imaging Signals in the Olfactory Bulb Are Independent of Neurovascular Coupling. AB - Functional brain-imaging techniques used in humans and animals, such as functional MRI and intrinsic optical signal (IOS) imaging, are thought to largely rely on neurovascular coupling and hemodynamic responses. Here, taking advantage of the well-described micro-architecture of the mouse olfactory bulb, we dissected the nature of odor-evoked IOSs. Using in vivo pharmacology in transgenic mouse lines reporting activity in different cell types, we show that parenchymal IOSs are largely independent of neurotransmitter release and neurovascular coupling. Furthermore, our results suggest that odor-evoked parenchymal IOSs originate from changes in light scattering of olfactory sensory neuron axons, mostly due to water movement following action potential propagation. Our study sheds light on a direct correlate of neuronal activity, which may be used for large-scale functional brain imaging. PMID- 26146076 TI - Regional Cell-Specific Transcriptome Mapping Reveals Regulatory Complexity in the Adult Drosophila Midgut. AB - Deciphering contributions of specific cell types to organ function is experimentally challenging. The Drosophila midgut is a dynamic organ with five morphologically and functionally distinct regions (R1-R5), each composed of multipotent intestinal stem cells (ISCs), progenitor enteroblasts (EBs), enteroendocrine cells (EEs), enterocytes (ECs), and visceral muscle (VM). To characterize cellular specialization and regional function in this organ, we generated RNA-sequencing transcriptomes of all five cell types isolated by FACS from each of the five regions, R1-R5. In doing so, we identify transcriptional diversities among cell types and document regional differences within each cell type that define further specialization. We validate cell-specific and regional Gal4 drivers; demonstrate roles for transporter Smvt and transcription factors GATAe, Sna, and Ptx1 in global and regional ISC regulation, and study the transcriptional response of midgut cells upon infection. The resulting transcriptome database (http://flygutseq.buchonlab.com) will foster studies of regionalization, homeostasis, immunity, and cell-cell interactions. PMID- 26146078 TI - Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic. AB - Woolly mammoths and living elephants are characterized by major phenotypic differences that have allowed them to live in very different environments. To identify the genetic changes that underlie the suite of woolly mammoth adaptations to extreme cold, we sequenced the nuclear genome from three Asian elephants and two woolly mammoths, and we identified and functionally annotated genetic changes unique to woolly mammoths. We found that genes with mammoth specific amino acid changes are enriched in functions related to circadian biology, skin and hair development and physiology, lipid metabolism, adipose development and physiology, and temperature sensation. Finally, we resurrected and functionally tested the mammoth and ancestral elephant TRPV3 gene, which encodes a temperature-sensitive transient receptor potential (thermoTRP) channel involved in thermal sensation and hair growth, and we show that a single mammoth specific amino acid substitution in an otherwise highly conserved region of the TRPV3 channel strongly affects its temperature sensitivity. PMID- 26146077 TI - The Regulatory Machinery of Neurodegeneration in In Vitro Models of Amyotrophic Lateral Sclerosis. AB - Neurodegenerative phenotypes reflect complex, time-dependent molecular processes whose elucidation may reveal neuronal class-specific therapeutic targets. The current focus in neurodegeneration has been on individual genes and pathways. In contrast, we assembled a genome-wide regulatory model (henceforth, "interactome"), whose unbiased interrogation revealed 23 candidate causal master regulators of neurodegeneration in an in vitro model of amyotrophic lateral sclerosis (ALS), characterized by a loss of spinal motor neurons (MNs). Of these, eight were confirmed as specific MN death drivers in our model of familial ALS, including NF-kappaB, which has long been considered a pro-survival factor. Through an extensive array of molecular, pharmacological, and biochemical approaches, we have confirmed that neuronal NF-kappaB drives the degeneration of MNs in both familial and sporadic models of ALS, thus providing proof of principle that regulatory network analysis is a valuable tool for studying cell specific mechanisms of neurodegeneration. PMID- 26146079 TI - Axon Dynamics during Neocortical Laminar Innervation. AB - The cerebral cortex is a densely interconnected structure with neural circuits that form between cortical laminae and also between distinct cortical areas. However, the precise cell biological and developmental mechanisms that underlie the formation of these neural circuits remain unknown. Here, we visualize laminar innervation of the developing mouse cerebral cortex by layer II/III pyramidal neurons in real time, describing cytoskeletal dynamics during this process. We find that layer II/III pyramidal neurons achieve local laminar-specific innervation through the stabilization of collateral axon branches in target laminae. We also find that loss of neural activity does not abolish local laminar specific innervation and that cells within the local environment are the likely source of cues that direct layer-specific cortical innervation. PMID- 26146080 TI - Cooperative Transcriptional Activation of Antimicrobial Genes by STAT and NF kappaB Pathways by Concerted Recruitment of the Mediator Complex. AB - The transcriptional response to infection with the bacterium Listeria monocytogenes (Lm) requires cooperative signals of the type I interferon (IFN-I) stimulated JAK-STAT and proinflammatory NF-kappaB pathways. Using ChIP-seq analysis, we define genes induced in Lm-infected macrophages through synergistic transcriptional activation by NF-kappaB and the IFN-I-activated transcription factor ISGF3. Using the Nos2 and IL6 genes as prime examples of this group, we show that NF-kappaB functions to recruit enzymes that establish histone marks of transcriptionally active genes. In addition, NF-kappaB regulates transcriptional elongation by employing the mediator kinase module for the recruitment of the pTEFb complex. ISGF3 has a major role in associating the core mediator with the transcription start as a prerequisite for TFIID and RNA polymerase II (Pol II) binding. Our data suggest that the functional cooperation between two major antimicrobial pathways is based on promoter priming by NF-kappaB and the engagement of the core mediator for Pol II binding by ISGF3. PMID- 26146081 TI - Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction. AB - Idiopathic pulmonary fibrosis (IPF) is a degenerative disease of the lungs with an average survival post-diagnosis of 2-3 years. New therapeutic targets and treatments are necessary. Mutations in components of the telomere-maintenance enzyme telomerase or in proteins important for telomere protection are found in both familial and sporadic IPF cases. However, the lack of mouse models that faithfully recapitulate the human disease has hampered new advances. Here, we generate two independent mouse models that develop IPF owing to either critically short telomeres (telomerase-deficient mice) or severe telomere dysfunction in the absence of telomere shortening (mice with Trf1 deletion in type II alveolar cells). We show that both mouse models develop pulmonary fibrosis through induction of telomere damage, thus providing proof of principle of the causal role of DNA damage stemming from dysfunctional telomeres in IPF development and identifying telomeres as promising targets for new treatments. PMID- 26146083 TI - Plant-Derived Tick Repellents Activate the Honey Bee Ectoparasitic Mite TRPA1. AB - We have identified and characterized the TRPA1 channel of Varroa destructor (VdTRPA1), a major ectoparasitic mite of honey bee. One of the two VdTRPA1 isoforms, VdTRPA1L, was activated by a variety of plant-derived compounds, including electrophilic compounds, suggesting that chemical activation profiles are mostly shared between arthropod TRPA1 channels. Nevertheless, carvacrol and alpha-terpineol activated VdTRPA1L but not a honey bee noxious-stimuli-sensitive TRPA, AmHsTRPA, and Drosophila melanogaster TRPA1. Activation of VdTRPA1L in D. melanogaster taste neurons by the above compounds was sufficient to modify the gustatory behaviors. Carvacrol and alpha-terpineol repelled V. destructor in a laboratory assay, and alpha-terpineol repressed V. destructor entry for reproduction into the brood cells in hives. Understanding the functions of parasite TRP channels not only gives clues about the evolving molecular and cellular mechanisms of parasitism but also helps in the development of control methods. PMID- 26146082 TI - CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid Derived Suppressor Cell Population and Function. AB - Our study reveals a non-canonical role for CCL2 in modulating non-macrophage, myeloid-derived suppressor cells (MDSCs) and shaping a tumor-permissive microenvironment during colon cancer development. We found that intratumoral CCL2 levels increased in patients with colitis-associated colorectal cancer (CRC), adenocarcinomas, and adenomas. Deletion of CCL2 blocked progression from dysplasia to adenocarcinoma and reduced the number of colonic MDSCs in a spontaneous mouse model of colitis-associated CRC. In a transplantable mouse model of adenocarcinoma and an APC-driven adenoma model, CCL2 fostered MDSC accumulation in evolving colonic tumors and enhanced polymorphonuclear (PMN)-MDSC immunosuppressive features. Mechanistically, CCL2 regulated T cell suppression of PMN-MDSCs in a STAT3-mediated manner. Furthermore, CCL2 neutralization decreased tumor numbers and MDSC accumulation and function. Collectively, our experiments support that perturbing CCL2 and targeting MDSCs may afford therapeutic opportunities for colon cancer interception and prevention. PMID- 26146084 TI - Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity. AB - Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H(+) leakage, and the fusion might contribute to invasiveness once a cell is transformed. PMID- 26146085 TI - Ca(2+) Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca(2+)-Dependent Nuclear Gene Expression. AB - In polarized cells or cells with complex geometry, clustering of plasma-membrane (PM) ion channels is an effective mechanism for eliciting spatially restricted signals. However, channel clustering is also seen in cells with relatively simple topology, suggesting it fulfills a more fundamental role in cell biology than simply orchestrating compartmentalized responses. Here, we have compared the ability of store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels confined to PM microdomains with a similar number of dispersed CRAC channels to activate transcription factors, which subsequently increase nuclear gene expression. For similar levels of channel activity, we find that channel confinement is considerably more effective in stimulating gene expression. Our results identify a long-range signaling advantage to the tight evolutionary conservation of channel clustering and reveal that CRAC channel aggregation increases the strength, fidelity, and reliability of the general process of excitation-transcription coupling. PMID- 26146086 TI - Semi-supervised Learning Predicts Approximately One Third of the Alternative Splicing Isoforms as Functional Proteins. AB - Alternative splicing acts on transcripts from almost all human multi-exon genes. Notwithstanding its ubiquity, fundamental ramifications of splicing on protein expression remain unresolved. The number and identity of spliced transcripts that form stably folded proteins remain the sources of considerable debate, due largely to low coverage of experimental methods and the resulting absence of negative data. We circumvent this issue by developing a semi-supervised learning algorithm, positive unlabeled learning for splicing elucidation (PULSE; http://www.kimlab.org/software/pulse), which uses 48 features spanning various categories. We validated its accuracy on sets of bona fide protein isoforms and directly on mass spectrometry (MS) spectra for an overall AU-ROC of 0.85. We predict that around 32% of "exon skipping" alternative splicing events produce stable proteins, suggesting that the process engenders a significant number of previously uncharacterized proteins. We also provide insights into the distribution of positive isoforms in various functional classes and into the structural effects of alternative splicing. PMID- 26146087 TI - Glutamate Receptor Modulation Is Restricted to Synaptic Microdomains. AB - A diverse array of neuromodulators governs cellular function in the prefrontal cortex (PFC) via the activation of G-protein-coupled receptors (GPCRs). However, these functionally diverse signals are carried and amplified by a relatively small assortment of intracellular second messengers. Here, we examine whether two distinct Galphai-coupled neuromodulators (norepinephrine and GABA) act as redundant regulators of glutamatergic synaptic transmission. Our results reveal that, within single dendritic spines of layer 5 pyramidal neurons, alpha-2 adrenergic receptors (alpha2Rs) selectively inhibit excitatory transmission mediated by AMPA-type glutamate receptors, while type B GABA receptors (GABA(B)Rs) inhibit NMDA-type receptors. We show that both modulators act via the downregulation of cAMP and PKA. However, by restricting the lifetime of active Galphai, RGS4 promotes the independent control of these two distinct target proteins. Our findings highlight a mechanism by which neuromodulatory microdomains can be established in subcellular compartments such as dendritic spines. PMID- 26146089 TI - A simple formula for the calculation of sample size in pilot studies. AB - One of the goals of a pilot study is to identify unforeseen problems, such as ambiguous inclusion or exclusion criteria or misinterpretations of questionnaire items. Although sample size calculation methods for pilot studies have been proposed, none of them are directed at the goal of problem detection. In this article, we present a simple formula to calculate the sample size needed to be able to identify, with a chosen level of confidence, problems that may arise with a given probability. If a problem exists with 5% probability in a potential study participant, the problem will almost certainly be identified (with 95% confidence) in a pilot study including 59 participants. PMID- 26146091 TI - How physical infusion system parameters cause clinically relevant dose deviations after setpoint changes. AB - Multi-infusion therapy, in which multiple pumps are connected to one access point, is frequently used in patient treatments. This practice is known to cause dosing errors following setpoint changes in the drug concentrations that actually enter the patients. Within the Metrology for Drug Delivery Project, we analyzed and quantified the two main physical phenomena leading to these errors: the "push out" effect and the system mechanical compliance. We compared the dosing errors of a three-pump system with two infusion sets, both with and without anti-reflux valves, using in vitro spectrophotometric experiments. Additionally, computer simulations were used to study the compliance effect separately. We found a start up time of more than 1 h, and a dosing error following a setpoint increase of another pump for the low flow rate pump, corresponding to 0.5 MUg noradrenaline delivered in 8 min. We showed that the dead volume inside the tubes and syringe compliance produce opposite deviations from the setpoint values in the actual drug output concentrations, making the net result hard to predict and often counterintuitive. We conclude that metrology on compliance and push-out effects could be used by infusion device manufacturers to successfully improve drug delivery performance and relevant standards for high-risk multi-infusion applications. PMID- 26146088 TI - Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte. AB - Sox9 encodes an essential transcriptional regulator of chondrocyte specification and differentiation. When Sox9 nuclear activity was compared with markers of chromatin organization and transcriptional activity in primary chondrocytes, we identified two distinct categories of target association. Class I sites cluster around the transcriptional start sites of highly expressed genes with no chondrocyte-specific signature. Here, Sox9 association reflects protein-protein association with basal transcriptional components. Class II sites highlight evolutionarily conserved active enhancers that direct chondrocyte-related gene activity through the direct binding of Sox9 dimer complexes to DNA. Sox9 binds through sites with sub-optimal binding affinity; the number and grouping of enhancers into super-enhancer clusters likely determines the levels of target gene expression. Interestingly, comparison of Sox9 action in distinct chondrocyte lineages points to similar regulatory strategies. In addition to providing insights into Sox family action, our comprehensive identification of the chondrocyte regulatory genome will facilitate the study of skeletal development and human disease. PMID- 26146092 TI - Influence of calibration method and material on the accuracy of stress distribution measurement systems. AB - Biomechanical analyses of the stress distribution and the force transfer in the human knee are essential to better understand the aetiology of joint diseases. Accuracy studies of commonly used capacitive or resistive-based stress distribution measurement systems have led to severe problems caused by an inaccurate experimental setup. For instance, in one study, overestimations of the measured forces in the sensor's centre were reported. Therefore, the primary aim of this study was to investigate the ability of capacitive and resistive-based sensors to measure forces in a homogenous pressure environment and the secondary goal was to analyse the influence of different calibration materials on the measurement accuracy. A Novel pressure vessel and metal indenters covered with different rubber materials were used in combination with a material testing machine to load the sensors. Four different linearly increasing nominal forces (925-3670 N) were applied and the deviations between the nominal and the measured forces were calculated. The capacitive measurement system showed errors between 1% and 7% in the homogenous pressure environment, whereas the errors of the resistive system were found to vary between 4% and 17%. The influence of the calibration material was observed to be greater for the resistive sensors (1 179%) than for the capacitive sensors (0.5-25%). In conclusion, it can be stated that - for the pressure measurement systems compared in this article - the capacitive one is less sensitive to the calibration method and the calibration material than the resistive system. PMID- 26146090 TI - Measuring drug exposure: concordance between defined daily dose and days' supply depended on drug class. AB - OBJECTIVES: To determine the concordance between two methods to measure drug exposure duration from pharmacy claim data. STUDY DESIGN AND SETTING: We conducted a cohort study using 2002-2007 US Medicaid data. Initiators of eight drug groups were identified: statins, metformin, atypical antipsychotics, warfarin, proton pump inhibitors (PPIs), angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (ns-NSAIDs), and coxibs. For each patient, we calculated two measures of exposure duration using (1) observed days' supply available in US pharmacy claims and (2) the World Health Organisation's Defined Daily Dose (DDD) methodology. We used Wilcoxon signed rank tests to compare medians and Spearman correlations to assess correlation between the two measures. RESULTS: Cohort sizes ranged from 143,885 warfarin users to >3,000,000 ns-NSAID users. Similar median exposure durations were observed for ACE inhibitors (70 days vs.75 days), PPIs (44 days vs. 45 days), and coxibs (44 days vs. 45 days). The DDD method overestimated exposure duration for ns-NSAIDs and underestimated for the remaining drug groups, relative to days' supply. Spearman correlation coefficients ranged from 0.2 to 0.8. CONCLUSION: Using DDDs to estimate drug exposure duration can result in misclassification. The magnitude of this misclassification might depend on doses used which can vary according to factors such as local prescribing practices, renal function, and age. PMID- 26146093 TI - The possibility of using magnetic nanoparticles to increase the therapeutic efficiency of Herceptin antibody. AB - INTRODUCTION: Herceptin is an expensive humanized antibody used for the treatment of early-stage breast cancers. This antibody can cause cardiotoxicity in some patients. In this study, we evaluated the possibility of increasing the therapeutic efficacy of Herceptin by combining magnetic nanoparticles and a permanent magnet for more accumulation in the tumor site. METHODS: Herceptin magnetic nanoparticles (HMNs) were synthesized and some of their characteristics, such as stability, magnetization, particle size by transmission electron microscopy (TEM), and dynamic light scattering (DLS) technique, were measured. The biodistribution study was checked in mice bearing breast tumor with and without a permanent magnet on the position of the tumor. The therapeutic effects of HMNs were considered in this condition. RESULTS: The size distribution of HMNs determined by the DLS technique was 182+/-7 nm and the average size by TEM was 100+/-10 nm. The reductions of 81% and 98% in the mean tumor volume for the group that received HMNs with magnetic field were observed at 42 and 45 days after injection, respectively. CONCLUSION: The good results in mice indicated that Herceptin-loaded iron oxide nanoparticles with external magnetic field have good potential for use in humans as a targeted drug delivery that needs more investigation. PMID- 26146094 TI - Magnetic nanoparticles adapted for specific biomedical applications. AB - Magnetic nanoparticles (MNPs) are used in different biomedical applications, whereby each application requires specific particle properties. To fulfill these requirements, particle properties have to be optimized by means of variation of crystal structure, particle size, and size distribution. To this aim, improved aqueous precipitation procedures for magnetic iron oxide nanoparticle synthesis were developed. One procedure focused on the cyclic growth of MNPs without nucleation of new particle cores during precipitation. The second novel particle type are magnetic multicore nanoparticles, which consist of single cores of approximately 10 nm forming dense clusters in the size range from 40 to 80 nm. Their highest potential features these multicore particles in hyperthermia application. In our in vivo experiments, therapeutically suitable temperatures were reached after 20 s of heating for a particle concentration in the tumor of 1% and field parameters of H=24 kA/m and f=410 kHz. This review on our recent investigations for particle optimization demonstrates that tuning magnetic properties of MNPs can be obtained by the alteration of their structure, size, and size distribution. This can be realized by means of control of particle size during synthesis or subsequent size-dependent fractionation. The here-developed particles show high potential for biomedical applications. PMID- 26146095 TI - Comparison of Total Tumor Volume, Size and Number of Colorectal Liver Metastases in Prediction of Survival in Patients after Liver Resection. AB - Liver is the most common location of the colorectal cancer metastases occurrence. Liver resection is the only curative method of treatment. Unfortunately it is feasible only in 25% of patients with colorectal liver metastases, often because of the extensiveness of the disease. The aim of the study was to evaluate the predictive value of total tumor volume, size and number of colorectal liver metastases in patients treated with right hemihepatectomy. MATERIAL AND METHODS: A retrospective analysis was performed in a group of 135 patients with colorectal liver metastases, who were treated with right hemihepatectomy. Total tumor volume was estimated based on the formula (4/3)pir3. Moreover, the study included an analysis of data on the number and size of tumors, radicality of the resection, time between primary tumor resection and liver resection, pre-operative blood serum concentration of carcinoembryonal antigen (CEA) and carcinoma antigen Ca 19 9. The predictive value of the factors was evaluated by applying a Cox proportional hazards model and the area under the ROC curve. RESULTS: The univariate analysis has shown the predictive value of size of the largest tumor (p=0.033; HR=1.065 per each cm) on the overall survival, however no predictive value of number of tumors (p=0.997; HR=1.000) and total tumor volume (p=0.212; HR=1.002) was observed. The multivariate analysis did not confirm the predictive value of the size of the largest tumor (p=0.141; HR=1.056). In the analysis of ROC curves, AUROC for the total tumor volume, the size of the largest tumor and the number of tumors were 0.629, 0.608, 0.520, respectively. CONCLUSIONS: Total tumor volume, size and number of liver metastases are not independent risk factors for the worse overall survival of patients with colorectal liver metastases treated with liver resection, therefore increased values of these factors should not be a contraindication for surgical treatment. PMID- 26146096 TI - Expression of the PLS3 Gene in Circulating Cells in Patients with Colorectal Cancer. AB - Circulating tumor cells (CTC) are cells in circulating blood that have the antigen and gene features of tumor cells of a specific type. Since they can be potentially used in diagnostics and monitoring of treatment of many tumors, they have been attracting attention of researchers worldwide. Plastin-3 (PL S3) is one of such markers of CTC. The aim of the study was to assess expression of PL S3 in CTC in patients with colorectal cancer, to conduct a statistical analysis and to demonstrate a link between expression of PL S3 and progress of the disease, level of CEA and Ca19-9 markers, gender and age of the patients. MATERIAL AND METHODS: A group of 85 patients of the Department of General and Colorectal Surgery of the Medical University in Lodz were enrolled in this study. Circulating tumor cells were isolated from whole blood of patients with colorectal cancer and an analysis of PL S3 gene expression in CTC was conducted. The next step was to conduct a statistical analysis and to demonstrate a link between expression of PL S3 in patients' CTC and progress of the disease, level of CEA and Ca 19-9 markers, gender and age of the patients. RESULTS: PL S3 is a marker which can be potentially used in prediction and monitoring of colorectal cancer. A link between expression of PL S3 in CTC of patients with colorectal cancer and metastasis to lymph nodes has been demonstrated. It may be of key importance how PL S3 could impact the qualification to supplementary cancer treatment in patients with stage II colorectal cancer. A link between expression of PL S3 gene in CTC and gender requires further in-depth studies. It is beyond doubt that PL S3 must be further investigated to determine its role in diagnostics, prediction, treatment and monitoring of treatment of colorectal cancer. PMID- 26146097 TI - The Value of Scoring Systems for the Diagnosis of Acute Appendicitis. AB - Accurate diagnosis of acute appendicitis (AA) is still a problem and is not always easy, even for experienced surgeons. Studies have shown that 20 to 30% of the appendices removedwere normal. Therefore, various scoring systems have been developed to aid in the diagnosis of doubtful cases and reduce the number of unnecessary appendectomies. The aim of this study was to assess the diagnostic value of different scoring systems in acute appendicitis. MATERIAL AND METHODS: The study involved 94 patients who underwent laparotomy due to suspected acute appendicitis. Medical examination at hospital admission was performed by a resident and a general surgery specialist. The probability of AA was evaluated using six different scoring systems: Alvarado, Fenyo, Eskelinen, Ohman, Tzankis, and RIPASA. The resident calculated the results in individual systems. The decision to perform the operation was taken by a specialist surgeon who did not know the results. RESULTS: Normal appendix was removed in 26% of cases. Eskelinen, RIPASA and Alvarado systems showed highest sensitivity (99%, 88% and 85%, respectively). Tzankis and Fenyo systems showed highest specificity (62% and 50%, respectively). CONCLUSIONS: Our study has shown limited value of scoring systems for the diagnosis of acute appendicitis. The systems may improve diagnostic accuracy as they require obtaining a more detailed medical history, and making a more thorough and organized data analysis. However, the scoring systems should be treated only as an aid to diagnosis. PMID- 26146098 TI - Immunomodelling Characteristics of Mature Dendritic Cells Stimulated by Colon Cancer Cells Lysates. AB - Application of cells with high TAA (tumor associated antigen) presentation potential seems to be crucial in neoplasia immunotherapy. Such feature is distributed in dendritic cells, which present peptides from processed TAA - MHC molecules complex to the T cells of a host. The aim of the study was to assess the influence of colon neoplasia tissue lysate on functioning of generated autologous DC's in the field of autologous CD4+ lymphocytes immunological response towards Th1/Th2 under in vitro environment together with comparison and assessment of DCs' immunosuppressive properties acquired from patients with colon cancer. MATERIAL AND METHODS: The population of this study consisted of 16 healthy- controls, 36colon cancer patients. Blood samples were collected 24h before planned surgery and preventive antibiotic therapy. Neoplastic tissue sample, was digested for cell lysates preparation. DC's generation from PBMC was carried out in standard conditionsand medium enriched with rhGM-CSF and rhIL-4. Mature DC's and cocultured autologous CD4 lymphocytes immunophenotype assessment was analyzed with flow cytometer. Intracellular and culture medium cytokines concentration was analyzed with ELISA and FACS method. RESULTS: DC's generated from colon cancer patients stimulated with lysates presented greater maturity, lower expression of CD206 antigen, significantly higher expression of HLA-DR, CD208 and CD209 and high intracellular expression of IL-12, compared to non stimulated cells. CONCLUSIONS: The neoplastic tissue in vivo produces a number of substances having an unfavorable effect on immune system, our results suggests using lysates as good dendritic cells stimulators that possibly could have application in colon cancer immunotherapy. PMID- 26146099 TI - The Role of the XPF Gene Polymorphism (Xrcc4) Ser835ser in the Risk of Malignant Transformation of Cells in the Colorectal Cancer. AB - Participation of DNA repair systems in the pathogenesis of cancer has been a suspected phenomenon for a long time. Decreased efficiency in DNA repair translates to their ability to fix and consequently leads to mutations and the process of carcinogenesis. Linking individual polymorphisms of DNA repair systems with an increased risk of colorectal cancer will allow the classification of patients to high-risk groups and their placement under preventive program. The aim of the study was to determine the effect of XPF gene polymorphism Ser835Ser on increasing the risk of colorectal cancer in the Polish population. MATERIAL AND METHODS: as the material blood collected from 146 patients diagnosed with colon cancer was used. The control group consisted of 149 healthy subjects. Genotyping was performed by Taq- Man method. RESULTS: The results indicate that genotype TCC/TCT is associated with an decreased risk of colorectal cancer (OR 0.574; CI 95% 0.335-0.984; p=0.043). CONCLUSIONS: Based on these results, we conclude that the XPF gene polymorphism Ser835Ser may be associated with a decreased risk of colorectal cancer. PMID- 26146100 TI - Familial Adenomatous Polyposis; 30-Year Observation of a Female Patient - Case Report. AB - Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome caused by a germline mutation inherited in an autosomal-dominant pattern with a 100% penetrance. Our detailed case report presents a history of a 55-year-old FAP female patient who had been under constant clinical observation for 30 years. The disease was diagnosed at the age of 22. The patient underwent restorative proctocolectomy with ileal pouch-anal anastomosis (PRC-IPAA). During our follow up extra-colonic manifestations occurred such as a desmoidtumour, fundic gland polyps in the stomach and duodenal polyps also in the periampullary region. Apart from disease-related symptoms the patient manifested other complications such as small bowel adhesive obstruction, benign breast tumours, uterine myomas, cholelithiasisand thyroid nodules. Our analysis of the above case presents advantages of a long-term medical observation of a FAP patient carried out by a specialist surgical medical centre. PMID- 26146101 TI - A Change of Traditional Method of Treatment of Partial Thickness Burn with Hydrofibre Dressings. AB - Nearly 1% of population is affected with burn trauma annually. Among patients seeking advanced medical care almost 8% require hospital stay. Most burns are superficial and do not cause full thickness damage to the skin. Standard topical treatment of burn wounds with creams and ointments requires frequent dressings' changes. The healing process is long and expensive. The technological revolution, as occurred in the last decade in the field of dressing care allows us to introduce the use of advanced material solutions. Modern materials allow to shorten the treatment time, reduce the expenses and diminish the patient discomfort leading to good outcome. The study presented a case of four patients treated due to the partial thickness burn wound. Hydrofiber dressing with silver ions were introduced in the treatment. We observed good short and long term results. PMID- 26146102 TI - Primary Adenocarcinoma in an Oesophageal Gastric Graft - Case Report. AB - Primary adenocarcinoma in the esophageal gastric graft is a rare complication diagnosed in patients with long-term survival. Most data concerning the diagnosis and treatment of patients with metachronic cancer in esophageal grafts is derived from Japan and South Korea. The diagnosis of cancer in esophageal gastric grafts in the European countries is rare. The study presented a case of a 66-year old male patient who, 30 months after an esophageal squamous cell cancer resection, was diagnosed with adenocarcinoma of the esophageal gastric graft. Despite control follow-up after the esophagectomy, cancer in the esophageal graft was detected during the stage that prevented performing radical surgery. The study presented the recommended diagnostic procedures and treatment options for esophageal gastric graft cancer, as well as review of available literature data. PMID- 26146103 TI - Tension-Free Mosquito Net Mesh Inguinal Hernioplasty - an Alternative Exclusively for the Third World? PMID- 26146104 TI - Assessment of the Results of Surgical Treatment of Zenker'S Diverticulum in Own Material. AB - Zenker diverticulum (ZD) is the most common type of diverticula of the esophagus. Most often refers to men with a peak incidence in the seventh and eighth decade of life. In the majority diverticula remains asymptomatic and in patients with symptomatic course of the disease symptoms are often nonspecific. Aim of the study was to present the authors' own experience in surgical treatment of Zenker diverticulum. MATERIAL AND METHODS: In this paper we present an analysis of 31 patients with confirmed ZD treated surgically at the Clinic in 2004-2014. Patients were analyzed in terms of age, gender, clinical symptoms, diverticulum size, type of surgery, the time to return to the oral intake, hospital stay and perioperative complications. RESULTS: 22 men and 9 women were enrolled it this study. The mean age of the patients was 64.8 (SD, 10.7; in the range of 28 to 82 years). 29 patients (93.5%) underwent resection of the diverticulum, while diverticulopexy was performed in two patients. In 25 (80.6%) cases stapler device was used, while in 4 (12.9%) resection was performed manually. The average size of resected diverticulum was 4.9 cm (SD, 1.5). Following the surgery in four patients (12.9%) complications were present. The average operating time was 118.7 minutes (SD, 42.2, in the range of 50 to 240 minutes). The mean length of hospital stay was 9.3 (SD, 3.3). CONCLUSIONS: Surgical treatment of ZD is associated with high effectiveness and low recurrence rate. Despite the advantages of endoscopic techniques, surgical treatment is characterized by one- stage procedure. The use of mechanical suture (stapler) significantly improves the operation, although on the basis of our own analysis there was no superiority revealed over hand sewn. Unquestionable adventage of classical technique is the opportunity to histopathological evaluation of resected diverticulum what is impossible to achieve in endoscopic techniques. PMID- 26146105 TI - The Influence of Micropauses on Surgeons' Precision After Short Laparoscopy Procedures. AB - It has recently been shown that micropauses during long surgical procedures can be beneficial for surgeons' precision and fatigue. The aim of the study was to evaluate the impact of micropauses on surgical precision measured by a simple smartphone application. MATERIAL AND METHODS: Two surgeons performed 40 simple laparoscopic procedures (appendectomy and cholecystectomy) with or without micropauses. After the operation the precision of surgical movements was measured by a simple smartphone application in which the number of successful trials and their mean time were used as a precision surrogate. RESULTS: Mean number of successful trials was significantly higher for appendectomy than for cholecystectomy (5.59 vs 4; p = 0.032). There was a difference between participating surgeons both in terms of number of successful trials (5.80 vs 3.55; p = 0.01) and a mean time of all successful trials (10.03 vs 6.28; p = 0.001). No other statistically significant differences were identified. CONCLUSION: Micropauses had no influence on surgical precision as evaluated after short laparoscopy procedures. The only differences were surgeon-dependent and intervention-dependent. PMID- 26146106 TI - Impact of APEX Ile64val Gene Polymorphisms of DNA Repair Ber System on Modulation of the Risk of Colorectal Cancer in the Polish Population. AB - Colorectal cancer (CRC) is one of the deadliest cancers which lie in the incidence of morbidity in second place. Intensive research is to determine and confirm the genetic basis of this disease, which is believed may have a direct relationship with the reduced efficiency of DNA repair systems. The aim of this study was to determine the effect of APEX gene polymorphism Ile64Val on increasing the risk of colorectal cancer in the Polish population. MATERIAL AND METHODS: The blood samples collected from 150 patients diagnosed with colon cancer was used. The control group consisted of 150 healthy subjects. Genotyping was performed by TaqMan method. RESULTS: The results indicate that genotype Ile Val is associated with an increased risk of colorectal cancer (OR 2.069; 95% CI 1,205-3,552; p = 0.008). CONCLUSIONS: Based on these results, we conclude that the APEX gene polymorphism Ile64Val may be associated with an increased risk of colorectal cancer. PMID- 26146107 TI - Influence of Obesity on Anastomotic Leakage After Anterior Rectal Resectionperformed Due to Cancer. AB - Anterior resection for rectal cancer carries the risk of serious complications, especially fistulas at the site of anastomosis. Numerous factors have been shown to impact anastomotic leakage. The results of studies on the influence of obesity on the frequency of anastomotic leakage after rectal resection performed due to cancer have been contradictory. The aim of the study was to evaluate the relationship between body mass index (BMI) and frequency of anastomotic leakage after anterior rectal resection performed due to cancer. MATERIAL AND METHODS: This retrospective analysis included 222 subsequent patients who had undergone anterior resection due to cancer with an anastomosis formed with a mechanical suture. The patients were divided into 3 groups depending on their BMI quartile as follows: Group I, BMI < 23.8 kg/m2 (lower quartile); group II, BMI between 23.8 and 29.38 kg/m2 (middle quartile); and group III, BMI > 29.38 kg/m2 (upper quartile). RESULTS: Anastomotic leakage occurred in 8 (3.6%) patients. Fistulas occurred in 4 out of 61 patients (6.56%) in group I, which was the highest incidence of fistulas for all 3 groups. In group II, fistulas occurred in 2 out of 55 patients (3.63%), and similarly, in group III, they occurred in 2 out of 106 patients (1.87%). The differences found in the frequency of fistulas between groups were not statistically significant (p=0.31). The logistic regression analysis did not show any relationship between leakage and age (p = 0.55; OR = 1.02; 95% CI: 0.95 - 1.1), sex (p = 0.97; OR = 0.97; 95% CI: 0.22 - 4.25) or BMI (p = 0.27; OR = 0.58; 95% CI: 0.22 - 1.53). CONCLUSIONS: The results of our study show that BMI did not have any influence on the frequency of anastomotic leakage after anterior rectal resection performed due to cancer. PMID- 26146108 TI - Is the Age of Patients with Iatrogenic Bile Duct Injuries Increasing? AB - Resection of the gall-bladder is still the most common surgical procedure performed at general surgery departments. The laparoscopic method used in the majority of cases offers considerable benefits but at the same time is associated with an increased rate of bile duct complications. So far, a slim female aged 25 50 years was a typical patient with a iatrogenic bile duct injury. The aim of the study was to identify the age of patients with iatrogenic bile duct injuries as well as the clinical course observed in recent years. MATERIAL AND METHODS: Gender and age structure of patients admitted to the Department of General, Transplant and Liver Surgery between the beginning of 2011 and June 2014 and treated for iatrogenic bile duct injuries, complications of laparoscopic cholecystectomy, were analysed. The patients were referred to the department as a reference centre. RESULTS: In the group of 186 patients, females predominated (69.4%) and the mean age was 52 years. A considerable increase in the mean age of patients treated in 2014 as compared with previous years was seen. This was related to an increased rate of bile duct injuries in patients aged over 70 years, who accounted for about 25% of the group. In previous years, bile duct injuries in patients of such an advanced age happened considerably less frequently. CONCLUSIONS: A iatrogenic bile duct injury in an elderly person may prove a fatal complication. A repair surgery, i.e. the biliary-enteric anastomosis, is a major and burdensome procedure, particularly in the case of patients aged over 70 years. Special caution during laparoscopic cholecystectomy is advised in this population, and the slightest doubts should lead to conversion. PMID- 26146109 TI - Surgical Correction of a Webbed-Neck Deformity in Turner'S Syndrome. AB - Turner's syndrome occurs in approximately 1 out of every 2,000 to 2,500 live-born girls. This genetically determined pathology is characterised by multiple congenital anomalies. A typical form of this syndrome is associated with a lack of one of the sex chromosomes (karyotype 45, X). From the point of view of plastic surgery, one of the most important elements of the therapy is correction of the webbed neck deformity. The aim of the study was to present the possibilities of surgical treatment of a webbed neck of patients with Turner's syndrome and the evaluation of treatment results. In the years 2000-2012, six children with Turner's syndrome were treated because of the webbed neck deformity. The age of patients ranged from 9 to 17 years. In the case of all patients, the aim was to distribute the neck skin folds by using Z-plasty in conjunction with a shift to the back of glabrous skin flaps mobilised from the anterolateral surface of the neck. In the case of four operated patients, the folds were completely removed and a correct symmetrical outline of the neck was obtained. One patient was found to have unilateral moderate webbed neck recurrence after about 2 years of treatment. In one case, the correction was insufficient. The performed surgical procedures enabled correction of low hairline only in the lateral parts of the neck. The lower line of the scalp in the central part of the neck has remained unchanged. The lateral approach with a shift of glabrous skin flap to the back, which we performed, allows for effective reduction of the webbed neck, excision of bands of the connective tissue and correction of the low hairline on the side of the neck. Z-plasty enables an adequate extension of scars and improves the contour of the neck. PMID- 26146110 TI - Management of Giant Hepatic Hemangioma in Atypical Localization; Report of a Case and Literature Review. AB - Hemangiomas are the most common benign primary hepatic neoplasms, often being incidentally discovered. In most of the cases they are small and asymptomatic. It is widely accepted that clinical intervention is indicated only for symptomatic hemangiomas. We present a case of an asymptomatic giant hemangioma managed by enucleation due to its atypical localization. The hemangioma, originally located in segment 5, was now described in Computer Tomography (CT) Imaging as separating the gallbladder from the liver parenchyma. A careful evaluation of images revealed proximity to the portal vein (PV), right hepatic artery (RHA), right hepatic duct (RHD) and right branch of the portal vein (RBPV). Thus, in the case of an emergent operation, surgical maneuvers in the area of the altered hepatic anatomy and proximity to the hemangioma itself, would in fact increase the risk endangering the patient's life. After patient's consent, a surgical enucleation en block with the gall-bladder was performed. It is of great importance that specifically selected, asymptomatic patients diagnosed with a giant hemangioma, with the above mentioned or similar localization should be considered for surgical treatment. PMID- 26146111 TI - The Application of Negative Pressure Wound Therapy with Installation in Diabetic Foot Associated with Phlegmon. AB - The negative pressure wound therapy in the treatment of diabetic foot ulcers was used successfully for many years. In the case of complications associated with infection by this type of wound treatment to give very good results. From many years of sustained research on a device that could combine the advantages of the negative pressure wound therapy and drainage flow. Finally, in the last year, the first V.A.C. Ulta (KCI, USA) devices were included to the Polish hospital departments. In this paper we present a case of a patient of successfully using a negative pressure wound therapy with installation via a set of V.A.C. Ulta in the ischemic diabetic foot syndrome complicated by phlegmon and tissue necrosis. The patient was treated in stages. In first stage was performed angioplasty of critically stenosis of the superficial femoral artery segment. Secondly, the resection of the necrotic bone revised fingers and forefoot was conducted, and in the third step the negative pressure wound therapy with installation was used. Finally, the wound was closed by the intermediate thickness skin graft. The total duration of treatment was 21 days. The patient in good general condition with a completely healed wound was discharged. Currently, after the supply with orthopedic equipment, patient regained full mobility. PMID- 26146112 TI - Colon Lymphomas - Rare Case of Intestinal Resection. PMID- 26146113 TI - Quality of life of patients on chronic parenteral nutrition before and after gastrointestinal tract continuity restoration. AB - The issue of the quality of life considering patients with a temporary or permanent intestinal stoma, as well as the necessity for chronic parenteral nutrition at home remain a poorly understood problem. Daily care of the intestinal stoma and the need to comply with sterile procedures required for parenteral nutrition require such patients to commit their time, which secondarily is associated with the broad aspects of social and personal life. The aim of the study was to analyse the quality of life considering patients with intestinal stomas subjected to chronic parenteral nutrition, before and after gastrointestinal tract continuity restoration. MATERIAL AND METHODS: The survey was conducted between May and July, 2014 on a group of 71 patients (33 female and 38 male) who were under the care of the Department of General Surgery and Clinical Nutrition, Warsaw Medical University, operated during the period between 2007 and July, 2014 with a present stoma (32 patients - 45%), as well as after stoma closure (39 patients - 55%). The analysed questionnaire contained 31 questions, and the SF-36 questionnaire was additionally used, determining the quality of life. RESULTS: Analysis of the study material showed differences in the quality of life, considering three most important determinants. Significantly worse assessment of the quality of life was reported by patients with a stoma and subject to intravenous nutrition (83.2+/-30.5), as compared to those after stoma closure subject to normal nutrition (52.3+/-33.8). Based on the SF-36 questionnaire differences between patients with a stoma and those without amounted to t(69)=2.84 (p=0.006) demonstrating that those with a stoma reported a lower quality of life. Analysis between younger and older patients, based on the SF-36 questionnaire (t(62.87)=2.49; p=0.016) showed that younger patients achieved lower results, considering dissatisfaction with life (61.55+/-27.5), as compared to the elderly (80.8+/-36.9). CONCLUSIONS: The group of patients without a stoma seem to be more independent- the vast majority do not use the help of family members (43.6%), or friends (64.1%). Patients with a stoma more often withdraw from social life. The factor that mostly reduces the quality of life is the presence of a stoma, which impairs daily functioning a lot more than the sterile procedures associated with parenteral nutrition. All patients after stoma closure consider that their overall functioning has significantly improved. PMID- 26146114 TI - Surgical methods of treatment of intestinal passage disturbances with the characteristics of constipation in patients with intestinal stoma based on own experience. AB - Stoma is an intestinal fistula created in emergency or by elective indications, and it is done to drain out the digestive tract content. In some patients there is a disturbance passage of gastric contents through the stoma, which may take the form of chronic constipation or even periodic subileus that will sooner or later require surgical treatment. The aim of the study was the assessment of the causes and method of treatment of constipation in patients with intestinal stoma. MATERIAL AND METHODS: A total of 331 patients with stoma followed by Ostomy and Proctology Outpatient Clinic were included in the study in the years 2011-2014. The study included 146 women and 185 men and the average age was 61.3 +/- 12.7 years. Within the entire froup, 273 patients had the end stoma performed whereas in 58 patients the loop stoma was created. The highest percentage of patients were the ones with diverticulosis and colorectal cancer, i.e. 132 and 114 patients respectively. A stoma was created in 35 patients due to inflammatory bowel disease (IBD), in 23 patients because of cancer, in 14 as a result of injuries and in 13 due to rectovaginal fistula. RESULTS: Out of the entire group subject to study (331 patients) 93 patients (28.1%) suffered from constipation. 50 patients with constipation required surgical intervention. The most common indication for surgical treatment was the parastomal hernia (36 patients, 72%), other indications were the narrowing of the stoma (5 patients, 10%), its collapse (6 patients, 12%) or prolapse (3 patients, 6%). Parastomal hernia was responsible for 84% of constipation within the stoma and 86.1% were treated with laparotomy (31 out of 36 patients). Other causes of constipation were the stomal stenoses (5 patients), collapse of the stoma (6 patients) and stomal prolapse (3 patients). All patients were treated surgically with a good final result. CONCLUSIONS: Constipation associated with dysfunction of the stoma in most cases should be treated surgically. Parastomal hernia is the most common cause of constipation in the stoma. Treatment should be performed in due time because of the possibility of developing complications, especially dangerous one is a strangulated parastomal hernia and ischemia of stoma. PMID- 26146115 TI - Analysis of complications after blood components' transfusions. AB - Complications after blood components still constitute an important clinical problem and serve as limitation of liberal-transfusion strategy. The aim of the study was to present the 5-year incidence of early blood transfusions complications and to assess their relation to the type of the transfused blood components. MATERIAL AND METHODS: 58,505 transfusions of blood components performed in the years 2006-2010 were retrospectively analyzed. Data concerning the amount of the transfused blood components and the numbers of adverse transfusion reactions reported to the Regional Blood Donation and Treatment Center (RBDTC) was collected. RESULTS: 95 adverse transfusion reactions were reportedto RBDTC 0.16% of alldonations (95/58 505) - 58 after PRBC transfusions, 28 after platelet concentrate transfusions and 9 after FFP transfusion. Febrile nonhemolytic and allergic reactions constitute respectively 36.8% and 30.5% of all complications. CONCLUSION: Nonhemolyticand allergic reactions are the most common complications of blood components transfusion and they are more common after platelet concentrate transfusions in comparison to PRBC and FFP donations. PMID- 26146116 TI - Evaluation of the quality of life of women treated due to breast cancer using amputation or breast conserving surgery in the early postoperative period. AB - Selection of the treatment method in breast cancer patients and its consequences may affect their quality of life through somatic, psychical, and social factors. The aim of the study was early evaluation of the quality of life of women after mastectomy vs. breast conserving surgery. MATERIAL AND METHODS: The study included 100 women aged 31 to 79 years (mean: 57) who underwent surgery due to breast cancer (amputation: 52; breast conserving surgery: 48 women) at the Cancer Centre in Bydgoszcz in 2014. The QLQ C-30 and QLQ BR-23 questionnaires were used to evaluate the quality of life of the patients 3 months after surgery. RESULTS: In the Global Health Status/QoL domain, the mean score for women after amputation and breast conserving surgery was 49 and 53, respectively; for Physical Functioning, the scores were 70 and 75, and for Role Functioning, 62 and 68, respectively. For Cognitive Functioning, the mean score was 74 and 73; for Emotional Functioning - 62 and 68, and for Social Functioning 64 and 60, respectively. The difference in the arm symptoms domain was significant at 46 and 33 points, respectively (p = 0.004). The patients treated with breast conserving surgery had a better body image than women after amputation - the mean score was 52 and 66, respectively (p = 0.01). CONCLUSIONS: With respect to Global Health Status/QoL and Physical Functioning, the quality of life of women in the early postoperative period was similar in women after breast amputation and those who underwent breast conserving surgery. Patients treated with breast conserving surgery had a better score for body image, while those who underwent amputation more often suffered from arm symptoms, such as pain, oedema, and problems with raising of the limb. PMID- 26146117 TI - Endovascular treatment of renal artery occlusion caused by aortic stentgraft migration. AB - Renal function impairment during interventional procedures became a real clinical problem. Contrast related nephropathy is the most common cause of renal failure, however, the procedure-related technical troubles may cause unexpected renal dysfunction.Technical failure of EVAR resulting in acute renal dysfunction is presented. The postprocedural occlusion of the right renal artery was treated in chimney technique. Early reintervention allowed the kidney preservation and renal function restoration. It is impossible to avoid all the complications following treatment of aortic aneurysm, but they can be anticipated and comprehensively treated in collaboration with other specialists. PMID- 26146118 TI - Multiannual abdominal pain complicated by obstruction of the gastrointestinal tract in the course of cystic form of mesenteric lymhangioma of the small intestine. AB - Lymphangiomas constitute a group of very rare diseases and occur with a frequency of 1/250,000 to 1/20,000 of hospitalizations. Even though they are benign lesions, their complications may turn into a life-threatening condition. They usually occur in children (90%), they are either congenital or they appear before the child's second birthday. Occassionally they are found in adults. Lymphangiomas are usually localized around neck, but also near armpits and in the groin area. Less than 1% of lymphagiomas are detected in the retroperitoneal space and intestinal mesentery. Vascular lesions derived from lymphatic vessels can be divided into ordinary ones, usually known as capillary, cavernous, and cystic. The cystic tumor (lymphangioma mesenteri) is the least common. It occurs mostly in the retroperitoneal space, mesentery of the colon, or extremely rarely in the mesentery of the small intestine. Preoperative diagnosis is difficult due to non-specific clinical symptoms and noncharacteristic image in the diagnostic tests. Lymphangioma complications, such as intestinal obstruction or perforation, and persistent pain, are the cause of exploratory laparotomy. Final diagnosis requires microscopic examination of material collected during an operation. This article presented the case of a 40-year-old female, operated due to the obstruction of the gastrointestinal tract, in whose case the lymphangioma was recognised in postoperative histopathological examination of the tumor from the jejunal mesentery. Since patients with these tumors have good chances of complete recovery - if there are no serious complications - it appears that the optimal therapeutic procedure should be early surgery, which reduces the possibility of complications. PMID- 26146119 TI - Neurogenic pulmonary edema induced by subarachnoid hemorrhage:; case report on diagnostic and therapeutic implications. AB - An exemplary rare case of neurogenic pulmonary edema induced by intracranial hemorrhage was reported including diagnostic and therapeutic implications as well as management recommendations. A 35-year old man who was treated first by a neurosurgical approach because of a subarachnoid hemorrhage (bore hole trepanation) and subsequently on a surgical intensive care unit because of severe postoperative hemodynamic, cardiocirculatory, and pulmonary disruptions. To monitor cardiopulmonary condition and treatment effects, a Swan-Ganz catheter was placed in the pulmonary artery, since after trepanation, a critical cardiopulmonary status developed during postoperative mechanical ventilation and catecholamine administration. This condition was indicated by neurogenic pulmonary edema detected by control chest X-ray film and high oxygen load in the inspiratory air required for sufficient arterial oxygenation. After use of high positive end-exspiratory pressure (PEEP) (initially directed against neurogenic lesion), adaptation of initial dobutamine doses, initiation of norepinephrine administration, and substitution of fluids, the patient's blood pressure finally rose sufficiently to sustain regular cerebral blood perfusion and achieve better arterial oxygenation. Thus, the patient's cardiopulmonary condition stabilized and temporary cardiac insufficiency could be overcome. Subsequently, it became possible to decrease PEEP according to requirements to prevent or limit cerebral edema and to diminish catecholamine doses. PMID- 26146120 TI - Role of electromyography and functional electrical stimulation in the treatment of anorectal diseases. PMID- 26146121 TI - Polish interdisciplinary consensus on diagnostics and treatment of colonic diverticulosis (2015). PMID- 26146122 TI - Erich Saling - The Father of Prenatal and Perinatal Medicine-Dedication to his 90th birthday. PMID- 26146123 TI - Phytochemical constituents as future antidepressants: a comprehensive review. AB - Depression is a major mental disease that is ranked as the fourth leading cause of disability. In order to avoid unwanted adverse reactions, as well as improve efficacy, current researches are seeking alternatives to conventional antidepressants. Phytochemicals provide an extensive research area in antidepressant therapies. The aim of the present study is to comprehensively review neurological evidences demonstrating the efficacy of phytochemicals in depression. For this purpose, electronic databases were searched to collect all data on the antidepressant mechanisms of phytochemicals from 1966 up to 2015. Plant metabolites from different categories including polyphenols (flavonoids, phenolic acids, lignanes, coumarins), alkaloids, terpenes and terpenoids, saponins and sapogenins, amines, and carbohydrates were found to possess antidepressant activity. Naringenin, quercetin derivatives, eugenol, piperine, diterpene alkaloids, berberine, hyperforin, riparin derivatives, ginsenosides, as well as beta-carboline alkaloids are among the most relevant ones. Naringenin has represented its antidepressant effect by elevation of serotonin (5-HT), norepinephrine, brain-derived neurotrophic factor (BDNF), and glucocorticoid receptors. Piperine demonstrated inhibition of monoamine oxidase enzymes, elevation of brain 5-HT and BDNF levels, and modulation of the hypothalamus pituitary-adrenal axis. The serotonergic, noradrenergic, and dopaminergic effect of berberine has been proven in several studies. Quercetin derivatives have revealed antidepressant potential via elevating pro-opiomelanocortin and neuroprotective properties, as well as reduction of proinflammatory cytokines. Assessing the structure-activity relationship of highly potent antidepressant phytochemicals is suggested to find future natural, semisynthetic, or synthetic antidepressants. Further clinical studies are also necessary for confirmation of natural antidepressant efficacy and completion of their safety profile. PMID- 26146124 TI - Mature coconut water exhibits antidiabetic and antithrombotic potential via L arginine-nitric oxide pathway in alloxan induced diabetic rats. AB - BACKGROUND: The aims of the present study were to assess whether the antidiabetic activity of mature coconut water (MCW) is mediated through L-arginine-nitric oxide pathway in diabetic rats, and to study the effects of MCW on blood coagulation. METHODS: Diabetes was induced in male Sprague-Dawley rats by injecting them with alloxan (150 mg/kg body weight). MCW (4 mL/100 g body weight) and L-arginine (7.5 mg/100 g body weight) was given orally for 45 days. L-NAME was given at a dose of 0.5 mg/kg body weight. Concentrations of blood glucose, plasma insulin, glycosylated hemoglobin (HbA1c), L-arginine, urine volume and urinary creatinine levels, activity of nitric oxide synthase (NOS), and arginase as well as the abnormalities in hemostasis and thrombosis were measured in all the experimental groups. RESULTS: Treatment with MCW and L-arginine reduced the concentration of blood glucose and HbA1c in diabetic rats. MCW and L-arginine treatment exhibited significant antithrombotic activity in diabetic rats, which was evident from the reduced levels of WBC, platelets, fibrin, and fibrinogen. MCW and L-arginine treatment prolonged the prothrombin time in diabetic rats and reduced the activity of Factor V. In addition to this, the activity of nitric oxide synthase, liver and plasma arginine content, and urinary nitrite were higher in MCW-treated diabetic rats whereas L-NAME treatment inhibited the beneficial effects induced by MCW and arginine. CONCLUSIONS: The results clearly indicate that L-arginine is a major factor responsible for the antidiabetic and antithrombotic potential of coconut water, and is mediated through the L-arginine nitric oxide pathway. PMID- 26146126 TI - Is Iron Chelation Important in Preventing Glycation of Bovine Serum Albumin in Vitro? AB - The role of metal (especially) iron ions has been postulated to play a prominent role in protein glycation, suggesting antiglycating effectiveness of metal chelators. However, this rule may not apply to all model glycation systems. We found that metal chelators are not effective in prevention of glycation of bovine serum albumin (BSA) in vitro, and there is no correlation between the antiglycating effects of 32 compounds and their iron chelation activity as measured with the ferrozine test. These data indicate that the glycation of BSA in vitro is iron-independent and is not a proper system to study the role of metals in protein glycation. PMID- 26146125 TI - The Transition of the 37-Kda Laminin Receptor (Rpsa) to Higher Molecular Weight Species: Sumoylation or Artifact? AB - The 37-kDa laminin receptor (37LRP or RPSA) is a remarkable, multifaceted protein that functions in processes ranging from matrix adhesion to ribosome biogenesis. Its ability to engage extracellular laminin is further thought to contribute to cellular migration and invasion. Most commonly associated with metastatic cancer, RPSA is also increasingly found to be important in other pathologies, including microbial infection, neurodegenerative disease and developmental malformations. Importantly, it is thought to have higher molecular weight forms, including a 67 kDa species (67LR), the expression of which is linked to strong laminin binding and metastatic behavior. The composition of these larger forms has remained elusive and controversial. Homo- and heterodimerization have been proposed as events capable of building the larger species from the monomeric 37-kDa precursor, but solid evidence is lacking. Here, we present data suggesting that higher molecular weight species require SUMOylation to form. We also comment on the difficulty of isolating larger RPSA species for unambiguous identification and demonstrate that cell lines stably expressing tagged RPSA for long periods of time fail to produce tagged higher molecular weight RPSA. It is possible that higher molecular weight species like 67LR are not derived from RPSA. PMID- 26146127 TI - The structure of Na+-translocating of NADH:ubiquinone oxidoreductase of Vibrio cholerae: implications on coupling between electron transfer and Na+ transport. AB - The Na+-translocating NADH:ubiquinone oxidoreductase (Na+-NQR) of Vibrio cholerae is a respiratory complex that couples the exergonic oxidation of NADH to the transport of Na+ across the cytoplasmic membrane. It is composed of six different subunits, NqrA, NqrB, NqrC, NqrD, NqrE, and NqrF, which harbor FAD, FMN, riboflavin, quinone, and two FeS centers as redox co-factors. We recently determined the X-ray structure of the entire Na+-NQR complex at 3.5-A resolution and complemented the analysis by high-resolution structures of NqrA, NqrC, and NqrF. The position of flavin and FeS co-factors both at the cytoplasmic and the periplasmic side revealed an electron transfer pathway from cytoplasmic subunit NqrF across the membrane to the periplasmic NqrC, and via NqrB back to the quinone reduction site on cytoplasmic NqrA. A so far unknown Fe site located in the midst of membrane-embedded subunits NqrD and NqrE shuttles the electrons over the membrane. Some distances observed between redox centers appear to be too large for effective electron transfer and require conformational changes that are most likely involved in Na+ transport. Based on the structure, we propose a mechanism where redox induced conformational changes critically couple electron transfer to Na+ translocation from the cytoplasm to the periplasm through a channel in subunit NqrB. PMID- 26146128 TI - Regulatory role of charged clusters in the N-terminal domain of BetP from Corynebacterium glutamicum. AB - The trimeric transporter BetP counteracts hyperosmotic stress by a fast increase in transport rate in order to accumulate the compatible solute betaine. The positively charged alpha-helical C-terminal domain acts as an osmosensor perceiving the increase in the internal potassium (K+) concentration. A second, still unidentified stimulus originates from stress-induced changes in the physical state of the membrane and depends on the amount of negatively charged lipids. BetP possesses a 60-amino acid (aa)-long negatively charged N-terminal domain, which is predicted to adopt a partly helical fold affecting osmoregulation by an unknown mechanism. It is assumed that the C-terminal domain, the N-terminal domain, and negatively charged lipids interact during stress sensing and regulation. Here, we have investigated the regulatory role of negatively charged clusters in the N-terminal domain. We identified one cluster, Glu24Glu25, to be crucial for osmoregulation. Cross-linking studies revealed an interaction between the C- and N-terminal domains of adjacent protomers modulating transport activation. A regulatory partner-switching mechanism emerges in which the C-terminal domain changes its interaction with the N-terminal domain of its own promoter and negatively charged lipids to an interaction with the N terminal domain of an adjacent protomer and lipids bound to the central cavity of the BetP trimer. PMID- 26146129 TI - Progress in chemical luminescence-based biosensors: A critical review. AB - Biosensors are a very active research field. They have the potential to lead to low-cost, rapid, sensitive, reproducible, and miniaturized bioanalytical devices, which exploit the high binding avidity and selectivity of biospecific binding molecules together with highly sensitive detection principles. Of the optical biosensors, those based on chemical luminescence detection (including chemiluminescence, bioluminescence, electrogenerated chemiluminescence, and thermochemiluminescence) are particularly attractive, due to their high-to-signal ratio and the simplicity of the required measurement equipment. Several biosensors based on chemical luminescence have been described for quantitative, and in some cases multiplex, analysis of organic molecules (such as hormones, drugs, pollutants), proteins, and nucleic acids. These exploit a variety of miniaturized analytical formats, such as microfluidics, microarrays, paper-based analytical devices, and whole-cell biosensors. Nevertheless, despite the high analytical performances described in the literature, the field of chemical luminescence biosensors has yet to demonstrate commercial success. This review presents the main recent advances in the field and discusses the approaches, challenges, and open issues, with the aim of stimulating a broader interest in developing chemical luminescence biosensors and improving their commercial exploitation. PMID- 26146130 TI - Risk of Misdiagnosis Due to Allele Dropout and False-Positive PCR Artifacts in Molecular Diagnostics: Analysis of 30,769 Genotypes. AB - Quality control is a complex issue for clinical molecular diagnostic applications. In the case of genotyping assays, artifacts such as allele dropout represent a risk of misdiagnosis for amplification-based methods. However, its frequency of occurrence in PCR-based diagnostic assays remains unknown. To maximize the likelihood of detecting allele dropout, our clinical genotyping PCR based assays are designed with two independent assays for each allele (nonoverlapping primers on each DNA strand). To estimate the incidence of allelic dropout, we took advantage of the capacity of our clinical assays to detect such events. We retrospectively studied their occurrence in the initial PCR assay for 30,769 patient reports for mutations involved in four diseases produced over 8 years. Ninety-three allele dropout events were detected and all were solved before reporting. In addition, 42 cases of artifacts caused by amplification of an allele ultimately confirmed to not be part of the genotype (drop-in events) were detected and solved. These artifacts affected 1:227 genotypes, 94% of which were due to nonreproducible PCR failures rather than sequence variants interfering with the assay, suggesting that careful primer design cannot prevent most of these errors. This provides a quantitative estimate for clinical laboratories to take this phenomenon into account in quality management and to favor assay designs that can detect (and minimize) occurrence of these artifacts in routine clinical use. PMID- 26146131 TI - Could sewage epidemiology be a strategy to assess lifestyle and wellness of a large scale population? AB - The use of sewage epidemiology to estimate the behavior of a large scale population has mainly been used to assess illicit drug use within a community. The systemic oxidative stress marker, 8-isoprostane, is a wildly accepted biomarker for various diseases such as diabetes, and cardiovascular and renal diseases. 8-Isoprostane is detected in urine and, as with illicit drugs, is excreted into urban sewer networks. Initially, we tested the hypothesis that differential 8-isoprostane levels are detected in wastewater of different communities and that 8-isoprostane values adjusted for the flow rate and population size will remain constant over a 2 months period. Sewage samples were collected from three sewage collection points supplied by different communities located in the Detroit metropolitan area and concentration of 8-isoprostane and synthetic plastic component, bisphenol A (BPA), were measured. Levels of 8 isoprostane were constant during the two measured months at each collection point in oppose to BPA levels. When the levels were compared among communities, 8 isoprostane levels in 24h flow and their concentrations per capita in each community varied by more than 5-fold among them. Considering the fact that 8 isoprostane is a biomarker of several diseases, we hypothesize that measurement of 8-isoprostane levels in sewage may serve as a risk assessment tool of oxidative stress-related diseases in a large scale population. Thus, sewage epidemiology can be utilized to obtain an early warning in a community to facilitate intervention for improvement of the community health. PMID- 26146132 TI - Causation model of autism: Audiovisual brain specialization in infancy competes with social brain networks. AB - Earliest identifiable findings in autism indicate that the autistic brain develops differently from the typical brain in the first year of life, after a period of typical development. Twin studies suggest that autism has an environmental component contributing to causation. Increased availability of audiovisual (AV) materials and viewing practices of infants parallel the time frame of the rise in prevalence of autism spectrum disorder (ASD). Studies have shown an association between ASD and increased TV/cable screen exposure in infancy, suggesting AV exposure in infancy as a possible contributing cause of ASD. Infants are attracted to the saliency of AV materials, yet do not have the experience to recognize these stimuli as socially relevant. The authors present a developmental model of autism in which exposure to screen-based AV input in genetically susceptible infants stimulates specialization of non-social sensory processing in the brain. Through a process of neuroplasticity, the autistic infant develops the skills that are driven by the AV viewing. The AV developed neuronal pathways compete with preference for social processing, negatively affecting development of social brain pathways and causing global developmental delay. This model explains atypical face and speech processing, as well as preference for AV synchrony over biological motion in ASD. Neural hyper connectivity, enlarged brain size and special abilities in visual, auditory and motion processing in ASD are also explained by the model. Positive effects of early intervention are predicted by the model. Researchers studying causation of autism have largely overlooked AV exposure in infancy as a potential contributing factor. The authors call for increased public awareness of the association between early screen viewing and ASD, and a concerted research effort to determine the extent of causal relationship. PMID- 26146133 TI - Ex-situ evaluation of bauxite residues as amendment for trace elements stabilization in dredged sediment from Mediterranean Sea: A case study. AB - Stabilization of marine dredged sediments contaminated with multi-elements is a challenging task in choosing the appropriate sorbent and application dosage. The present study investigates the possibility of using bauxite residues (Bauxaline(r) and Bauxsol) as amendment for the treatment of contaminated sediment. A pilot scale experiment was conducted for three months to stabilize trace elements in composted contaminated sediment sample using 5% by-product amendment. The results showed that after 3months of treatment, cationic trace elements were effectively immobilized but increased leaching of anionic pollutants was observed. Increased leaching of anionic pollutants could be limited by addition of higher quantities of amendments. The total content of available pollutants decreased in stabilized sediments but this treatment has no effect on the classification of waste. The leachates were then evaluated for acute toxicity using estuarine rotifers Brachionus plicatilis. Bauxite residues can be inexpensive choices for the stabilization of cationic pollutants in dredged sediments. PMID- 26146134 TI - Historical trends (1998-2012) of nickel (Ni), copper (Cu) and chromium (Cr) concentrations in marine sediments at four locations in the Northern Adriatic Sea. AB - Historical trends (1998-2012) nickel (Ni), copper (Cu) and chromium (Cr) concentrations in marine sediments were assessed at four locations in the Northern Adriatic Sea (Croatia) in the proximity of an oil refinery. Ecological risks were characterized by benchmarking the dataset against Sediment Quality Guidelines (SQG). A significant number of samples had Ni values above ERL with no exceedance of the ERL values for Cu and Cr. Weak positive historical trends were found for only for Cu. At all sites there were statistically significant correlations between Ni and Cr indicating a common origin of these heavy metals in the investigated marine sediments. There were statistically significant differences between the sites under the direct influence of the oil refinery compared to the control site indicating the possibility that the oil refinery is contributing to the concentration of these heavy metals in the marine sediments. PMID- 26146135 TI - Hemodilution Combined With Hypercapnia Impairs Cerebral Autoregulation During Normothermic Cardiopulmonary Bypass. AB - OBJECTIVE: To investigate the influence of hemodilution and arterial pCO2 on cerebral autoregulation and cerebral vascular CO2 reactivity. DESIGN: Prospective interventional study. SETTING: University hospital-based single-center study. PARTICIPANTS: Forty adult patients undergoing elective cardiac surgery using normothermic cardiopulmonary bypass. INTERVENTIONS: Blood pressure variations induced by 6/minute metronome-triggered breathing (baseline) and cyclic 6/min changes of indexed pump flow at 3 levels of arterial pCO2. MEASUREMENTS AND MAIN RESULTS: Based on median hematocrit on bypass, patients were assigned to either a group of a hematocrit >=28% or<28%. The autoregulation index was calculated from cerebral blood flow velocity and mean arterial blood pressure using transfer function analysis. Cerebral vascular CO2 reactivity was calculated using cerebral tissue oximetry data. Cerebral autoregulation as reflected by autoregulation index (baseline 7.5) was significantly affected by arterial pCO2 (median autoregulation index amounted to 5.7, 4.8, and 2.8 for arterial pCO2 of 4.0, 5.3, and 6.6 kPa, p<=0.002) respectively. Hemodilution resulted in a decreased autoregulation index; however, during hypocapnia and normocapnia, there were no significant differences between the two hematocrit groups. Moreover, the autoregulation index was lowest during hypercapnia when hematocrit was<28% (autoregulation index 3.3 versus 2.6 for hematocrit >=28% and<28%, respectively, p = 0.014). Cerebral vascular CO2 reactivity during hypocapnia was significantly lower when perioperative hematocrit was<28% (p = 0.018). CONCLUSIONS: Hemodilution down to a hematocrit of<28% combined with hypercapnia negatively affects dynamic cerebral autoregulation, which underlines the importance of tight control of both hematocrit and paCO2 during CPB. PMID- 26146136 TI - Tracheostomy After Cardiac Surgery With Median Sternotomy and Risk of Deep Sternal Wound Infections: Is It a Matter of Timing? AB - OBJECTIVE: To assess the impact of timing of percutaneous dilatational tracheotomy (PDT) on incidence of deep sternal wound infections (DSWI) after cardiac surgery with median sternotomy. DESIGN: Retrospective study between 2003 and 2013. SETTING: Single-center university hospital. PARTICIPANTS: Eight hundred seventy-nine patients after cardiac surgery with extracorporeal circulation and median sternotomy. INTERVENTIONS: PDT using the Ciaglia-technique with direct bronchoscopic guidance. MEASUREMENT AND MAIN RESULTS: Mean time from surgery and (re)intubation to PDT was 6.7+/-9.9 and 3.8+/-3.3 days, respectively. Incidence of DSWI was 3.9% (34/879). The incidence of DSWI was comparable between patients with PDT performed before postoperative day (POD) 10 and those with PDT after POD 10 (29/755 [3.8%] v 5/124 [4.0%], p = n.s.). However, the authors observed an association of timing of PDT and DSWI: The incidence of DSWI was significantly higher in patients with PDT performed<=POD 1 compared to those with PDT after POD 2 (12/184 [6.52%] v 22/695 [3.16%], p = 0.046). In multivariate analysis, obesity, use of bilateral internal mammary arteries, ICU stay>30 days and PDT<48 hours after surgery (OR 3.519, 95% CI 1.242-9.976, p = 0.0018) were independent predictors of DSWI. In 15/34 patients (44.1%), similarity of microorganisms between sternotomy site and tracheal cultures was observed, indicating a possible cross-contamination. CONCLUSIONS: PDT within the first 10 postoperative days after cardiac surgery with median sternotomy can be performed safely without an increased risk of DSWI. In contrast, very early PDT within 48 hours after surgery is associated with an increased risk of mediastinitis and should, therefore, be avoided. PMID- 26146137 TI - Lithium ion dynamics in Li2S+GeS2+GeO2 glasses studied using (7)Li NMR field cycling relaxometry and line-shape analysis. AB - We use (7)Li NMR to study the ionic jump motion in ternary 0.5Li2S+0.5[(1 x)GeS2+xGeO2] glassy lithium ion conductors. Exploring the "mixed glass former effect" in this system led to the assumption of a homogeneous and random variation of diffusion barriers in this system. We exploit that combining traditional line-shape analysis with novel field-cycling relaxometry, it is possible to measure the spectral density of the ionic jump motion in broad frequency and temperature ranges and, thus, to determine the distribution of activation energies. Two models are employed to parameterize the (7)Li NMR data, namely, the multi-exponential autocorrelation function model and the power-law waiting times model. Careful evaluation of both of these models indicates a broadly inhomogeneous energy landscape for both the single (x=0.0) and the mixed (x=0.1) network former glasses. The multi-exponential autocorrelation function model can be well described by a Gaussian distribution of activation barriers. Applicability of the methods used and their sensitivity to microscopic details of ionic motion are discussed. PMID- 26146156 TI - A novel method based on physicochemical properties of amino acids and one class classification algorithm for disease gene identification. AB - Identifying the genes that cause disease is one of the most challenging issues to establish the diagnosis and treatment quickly. Several interesting methods have been introduced for disease gene identification for a decade. In general, the main differences between these methods are the type of data used as a prior knowledge, as well as machine learning (ML) methods used for identification. The disease gene identification task has been commonly viewed by ML methods as a binary classification problem (whether any gene is disease or not). However, the nature of the data (since there is no negative data available for training or leaners) creates a major problem which affect the results. In this paper, sequence-based, one class classification method is introduced to assign genes to disease class (yes, no). First, to generate feature vector, the sequences of proteins (genes) are initially transformed to numerical vector using physicochemical properties of amino acid. Second, as there is no definite approach to define non-disease genes (negative data); we have attempted to model solely disease genes (positive data) to make a prediction by employing Support Vector Data Description algorithm. The experimental results confirm the efficiency of the method with precision, recall and F-measure of 79.3%, 82.6% and 80.9%, respectively. PMID- 26146157 TI - A privacy preserving protocol for tracking participants in phase I clinical trials. AB - OBJECTIVE: Some phase 1 clinical trials offer strong financial incentives for healthy individuals to participate in their studies. There is evidence that some individuals enroll in multiple trials concurrently. This creates safety risks and introduces data quality problems into the trials. Our objective was to construct a privacy preserving protocol to track phase 1 participants to detect concurrent enrollment. DESIGN: A protocol using secure probabilistic querying against a database of trial participants that allows for screening during telephone interviews and on-site enrollment was developed. The match variables consisted of demographic information. MEASUREMENT: The accuracy (sensitivity, precision, and negative predictive value) of the matching and its computational performance in seconds were measured under simulated environments. Accuracy was also compared to non-secure matching methods. RESULTS: The protocol performance scales linearly with the database size. At the largest database size of 20,000 participants, a query takes under 20s on a 64 cores machine. Sensitivity, precision, and negative predictive value of the queries were consistently at or above 0.9, and were very similar to non-secure versions of the protocol. CONCLUSION: The protocol provides a reasonable solution to the concurrent enrollment problems in phase 1 clinical trials, and is able to ensure that personal information about participants is kept secure. PMID- 26146158 TI - Optimization of drug regimen in chemotherapy based on semi-mechanistic model for myelosuppression. AB - Based on the latest statistics on trends in cancer incidence and mortality worldwide, cancer burden is growing at an alarming pace. Many anticancer drugs have been proved effective against cancer cells as well as toxic to human tissues, which prevents sufficient doses from being administered to obtain a complete cure. In this paper we build an optimal control model to optimize the scheduling problem along one cycle of chemotherapy treatment using a single anticancer drug etoposide (VP-16). In the model, three mathematic models are adopted to mimic physiological response of body under chemotherapy: (i) Pharmacokinetic model of anticancer drug; (ii) A two-compartment tumor growth dynamic model under the influence of cell-cycle-specific anticancer drugs; and (iii) A semi-mechanistic model for myelosuppression. In this new integrated model clinically relevant objectives are proposed to gain a trade-off between efficacy and toxicity. Simulation results of clinical protocols are consistent with real life clinical data. Furthermore, we find a new optimal drug regimen which can improve the efficacy without the risk of severe toxicity. PMID- 26146159 TI - Mining and exploring care pathways from electronic medical records with visual analytics. AB - OBJECTIVE: In order to derive data-driven insights, we develop Care Pathway Explorer, a system that mines and visualizes a set of frequent event sequences from patient EMR data. The goal is to utilize historical EMR data to extract common sequences of medical events such as diagnoses and treatments, and investigate how these sequences correlate with patient outcome. MATERIALS AND METHODS: The Care Pathway Explorer uses a frequent sequence mining algorithm adapted to handle the real-world properties of EMR data, including techniques for handling event concurrency, multiple levels-of-detail, temporal context, and outcome. The mined patterns are then visualized in an interactive user interface consisting of novel overview and flow visualizations. RESULTS: We use the proposed system to analyze the diagnoses and treatments of a cohort of hyperlipidemic patients with hypertension and diabetes pre-conditions, and demonstrate the clinical relevance of patterns mined from EMR data. The patterns that were identified corresponded to clinical and published knowledge, some of it unknown to the physician at the time of discovery. CONCLUSION: Care Pathway Explorer, which combines frequent sequence mining techniques with advanced visualizations supports the integration of data-driven insights into care pathway discovery. PMID- 26146160 TI - The role of timing of maltreatment and child intelligence in pathways to low symptoms of depression and anxiety in adolescence. AB - Research indicates that childhood maltreatment is strongly associated with high levels of adolescent depression and anxiety symptoms. Using LONGSCAN data and taking into account the range of family characteristics related to adversity (poverty, primary caregiver substance abuse) and protective factors (living with biological mother and father), the present study assessed the complex resilience process in which child intelligence (age 6) mediated the relationship between early childhood maltreatment (age 0-4) and adolescent symptoms of depression and anxiety (age 14). We also assessed if mid (age 6-8) and late (age 10-12) childhood maltreatment moderated this mediation. We found that mid-childhood intelligence mediated the negative effect of early childhood maltreatment (age 0 4) on anxiety symptoms (age 14), but not on depressive symptoms (age 14). We also found the effect of timing of maltreatment: early childhood maltreatment (age 0 4) predicted more anxiety symptoms in adolescence, whereas late childhood/early adolescent (age 10-12) maltreatment predicted more symptoms of depression in adolescence. In addition, mid (age 6-8) and late (age 10-12) childhood maltreatment dampened the protective effect of IQ (age 6) against anxiety (age 14). In sum, current evidence shows that low anxiety and depression symptoms in adolescence following childhood maltreatment was achieved through different pathways, and that early and late childhood/early adolescence were more sensitive periods for development of psychopathology related to depression and anxiety in adolescence. PMID- 26146161 TI - Determining women's sexual self-schemas through advanced computerized text analysis. AB - The meaning extraction method (MEM), an advanced computerized text analysis technique, was used to analyze women's sexual self-schemas. Participants (n=239) completed open-ended essays about their personal feelings associated with sex and sexuality. These essays were analyzed using the MEM, a procedure designed to extract common themes from natural language. Using the MEM procedure, we extracted seven unique themes germane to sexual self-schemas: family and development, virginity, abuse, relationship, sexual activity, attraction, and existentialism. Each of these themes is comprised of frequently used words across the participants' descriptions of their sexual selves. Significant differences in sexual self-schemas were observed to covary with age, relationship status, and sexual abuse history. PMID- 26146162 TI - Sexual dimorphism of the mandible in a contemporary Chinese Han population. AB - A present limitation of forensic anthropology practice in China is the lack of population-specific criteria on contemporary human skeletons. In this study, a sample of 203 maxillofacial Cone beam computed tomography (CBCT) images, including 96 male and 107 female cases (20-65 years old), was analyzed to explore mandible sexual dimorphism in a population of contemporary adult Han Chinese to investigate the potential use of the mandible as sex indicator. A three dimensional image from mandible CBCT scans was reconstructed using the SimPlant Pro 11.40 software. Nine linear and two angular parameters were measured. Discriminant function analysis (DFA) and logistic regression analysis (LRA) were used to develop the mathematics models for sex determination. All of the linear measurements studied and one angular measurement were found to be sexually dimorphic, with the maximum mandibular length and bi-condylar breadth being the most dimorphic by univariate DFA and LRA respectively. The cross-validated sex allocation accuracies on multivariate were ranged from 84.2% (direct DFA), 83.5% (direct LRA), 83.3% (stepwise DFA) to 80.5% (stepwise LRA). In general, multivariate DFA yielded a higher accuracy and LRA obtained a lower sex bias, and therefore both DFA and LRA had their own advantages for sex determination by the mandible in this sample. These results suggest that the mandible expresses sexual dimorphism in the contemporary adult Han Chinese population, indicating an excellent sexual discriminatory ability. Cone beam computed tomography scanning can be used as alternative source for contemporary osteometric techniques. PMID- 26146163 TI - Impacts of climate change on precipitation and discharge extremes through the use of statistical downscaling approaches in a Mediterranean basin. AB - Mediterranean region is characterized by high precipitation variability often enhanced by orography, with strong seasonality and large inter-annual fluctuations, and by high heterogeneity of terrain and land surface properties. As a consequence, catchments in this area are often prone to the occurrence of hydrometeorological extremes, including storms, floods and flash-floods. A number of climate studies focused in the Mediterranean region predict that extreme events will occur with higher intensity and frequency, thus requiring further analyses to assess their effect at the land surface, particularly in small- and medium-sized watersheds. In this study, climate and hydrologic simulations produced within the Climate Induced Changes on the Hydrology of Mediterranean Basins (CLIMB) EU FP7 research project were used to analyze how precipitation extremes propagate into discharge extremes in the Rio Mannu basin (472.5km(2)), located in Sardinia, Italy. The basin hydrologic response to climate forcings in a reference (1971-2000) and a future (2041-2070) period was simulated through the combined use of a set of global and regional climate models, statistical downscaling techniques, and a process based distributed hydrologic model. We analyzed and compared the distribution of annual maxima extracted from hourly and daily precipitation and peak discharge time series, simulated by the hydrologic model under climate forcing. For this aim, yearly maxima were fit by the Generalized Extreme Value (GEV) distribution using a regional approach. Next, we discussed commonality and contrasting behaviors of precipitation and discharge maxima distributions to better understand how hydrological transformations impact propagation of extremes. Finally, we show how rainfall statistical downscaling algorithms produce more reliable forcings for hydrological models than coarse climate model outputs. PMID- 26146164 TI - Film-Stabilizing Attributes of Polymeric Core-Shell Nanoparticles. AB - Self-organization of nanoparticles into stable, molecularly thin films provides an insightful paradigm for manipulating the manner in which materials interact at nanoscale dimensions to generate unique material assemblies at macroscopic length scales. While prior studies in this vein have focused largely on examining the performance of inorganic or organic/inorganic hybrid nanoparticles (NPs), the present work examines the stabilizing attributes of fully organic core-shell microgel (CSMG) NPs composed of a cross-linked poly(ethylene glycol dimethacrylate) (PEGDMA) core and a shell of densely grafted, but relatively short-chain, polystyrene (PS) arms. Although PS homopolymer thin films measuring from a few to many nanometers in thickness, depending on the molecular weight, typically dewet rapidly from silica supports at elevated temperatures, spin coated CSMG NP films measuring as thin as 10 nm remain stable under identical conditions for at least 72 h. Through the use of self-assembled monolayers (SAMs) to alter the surface of a flat silica-based support, we demonstrate that such stabilization is not attributable to hydrogen bonding between the acrylic core and silica. We also document that thin NP films consisting of three or less layers (10 nm) and deposited onto SAMs can be fully dissolved even after extensive thermal treatment, whereas slightly thicker films (40 nm) on Si wafer become only partially soluble during solvent rinsing with and without sonication. Taken together, these observations indicate that the present CSMG NP films are stabilized primarily by multidirectional penetration of relatively short, unentangled NP arms caused by NP layering, rather than by chain entanglement as in linear homopolymer thin films. This nanoscale "velcro"-like mechanism permits such NP films, unlike their homopolymer counterparts of comparable chain length and thickness, to remain intact as stable, free-floating sheets on water, and thus provides a viable alternative to ultrathin organic coating strategies. PMID- 26146165 TI - Hybrid male sterility and genome-wide misexpression of male reproductive proteases. AB - Hybrid male sterility is a common barrier to gene flow between species. Previous studies have posited a link between misregulation of spermatogenesis genes in interspecies hybrids and sterility. However, in the absence of fully fertile control hybrids, it is impossible to differentiate between misregulation associated with sterility vs. fast male gene regulatory evolution. Here, we differentiate between these two possibilities using a D. pseudoobscura species pair that experiences unidirectional hybrid sterility. We identify genes uniquely misexpressed in sterile hybrid male reproductive tracts via RNA-seq. The sterile male hybrids had more misregulated and more over or under expressed genes relative to parental species than the fertile male hybrids. Proteases were the only gene ontology class overrepresented among uniquely misexpressed genes, with four located within a previously identified hybrid male sterility locus. This result highlights the potential role of a previously unexplored class of genes in interspecific hybrid male sterility and speciation. PMID- 26146182 TI - Use of standardized uptake value thresholding for target volume delineation in pediatric Hodgkin lymphoma. AB - PURPOSE: A limitation of [(18)F] 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDGPET) in radiation planning for Hodgkin lymphoma (HL) is significant variability in delineation of tumor volume. One approach to reduce variability is to apply automatic or semiautomatic segmentation methods such as thresholding based on a percent tumor maximum standardized uptake value (SUVmax). Here, we apply various tumor SUVmax thresholds and examine their effects in involved field radiation therapy (IFRT) and involved site radiation therapy (ISRT) target volumes. METHODS AND MATERIALS: PET/computed tomography data sets were reviewed for 16 pediatric and young adult patients treated with IFRT. The following percent tumor SUVmax thresholds were applied to the prechemotherapy PET: 15%, 20%, 25%, 30%, 35%, and 40%. Clinical target volumes for IFRT and ISRT plans were manually generated based on these threshold volumes (CTVPET) and compared with clinical target volumes generated using the standard qualitative visual method (CTVQVM). Treatment plans were generated, doses to normal structures were compared, and the optimum threshold, defined as the CTVPET that corresponded to the percent overlap closest to 100% when compared with the CTVQVM, was determined. RESULTS: On average, there was a 7.6-fold increase in PET volume between 40% and 15% SUVmax. When the 6 SUVmax thresholds were applied in the design of target volumes for IFRT, 2 of 16 patients had a change in treatment volume. There was a 2.4-fold increase in ISRT CTVs generated based on the 15% and 40% SUVmax, which translated into a clinically significant decrease in dose to normal structures when the ISRT plans that were generated using the 15% SUVmax volumes were compared with the 40% SUVmax. In most patients, the optimum threshold was SUVmax 15%. CONCLUSIONS: Accurate target volume delineation with [(18)F] 2-fluoro-2-deoxy-d-glucose PET in HL is challenging and may require more precise and reproducible segmentation methods as we move toward more conformal therapies. PMID- 26146183 TI - Facts and promises on lung biomarkers in interstitial lung diseases. AB - Interstitial lung diseases (ILDs) are a heterogeneous group of >100 pulmonary disorders. ILDs are characterized by an irreversible architectural distortion and impaired gas exchange; however, there is great variability in the clinical course. ILD diagnosis requires a combination of clinical data, radiological imaging and histological findings (when a lung biopsy is required). At the same time, successful management of ILD patients strictly depends on an accurate and confident diagnosis. In this context, the detection of reliable biomarkers able to identify ILD subtypes, avoiding lung biopsy, as well as the capacity to stratify patients and predict over time the disease course, has become a primary aim for all research studies in this field. PMID- 26146184 TI - Molecular Characterization of LubX: Functional Divergence of the U-Box Fold by Legionella pneumophila. AB - LubX is part of the large arsenal of effectors in Legionella pneumophila that are translocated into the host cytosol during infection. Despite such unique features as the presence of two U-box motifs and its targeting of another effector SidH, the molecular basis of LubX activity remains poorly understood. Here we show that the N terminus of LubX is able to activate an extended number of ubiquitin conjugating (E2) enzymes including UBE2W, UBEL6, and all tested members of UBE2D and UBE2E families. Crystal structures of LubX alone and in complex with UBE2D2 revealed drastic molecular diversification between the two U-box domains, with only the N-terminal U-box retaining E2 recognition features typical for its eukaryotic counterparts. Extensive mutagenesis followed by functional screening in a yeast model system captured functionally important LubX residues including Arg121, critical for interactions with SidH. Combined, these data provide a new molecular insight into the function of this unique pathogenic factor. PMID- 26146186 TI - Fully Blind Peptide-Protein Docking with pepATTRACT. AB - Peptide-protein interactions are ubiquitous in the cell and form an important part of the interactome. Computational docking methods can complement experimental characterization of these complexes, but current protocols are not applicable on the proteome scale. Here, we present a new fully blind flexible peptide-protein docking protocol, pepATTRACT, which combines a rapid coarse grained global peptide docking search of the entire protein surface with a two stage atomistic flexible refinement. Global unbound-unbound docking yielded near native models for 70% of the docking cases when testing the protocol on the largest benchmark of peptide-protein complexes available to date. This performance is similar to that of state-of-the-art local docking protocols that rely on information about the binding site. Upon restricting the search to the peptide binding region, the resulting pepATTRACT-local approach outperformed existing methods. Docking scripts for pepATTRACT and pepATTRACT-local can be generated via a web interface at www.attract.ph.tum.de/peptide.html. PMID- 26146185 TI - Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction. AB - CD6 is a transmembrane protein with an extracellular region containing three scavenger receptor cysteine rich (SRCR) domains. The membrane proximal domain of CD6 binds the N-terminal immunoglobulin superfamily (IgSF) domain of another cell surface receptor, CD166, which also engages in homophilic interactions. CD6 expression is mainly restricted to T cells, and the interaction between CD6 and CD166 regulates T-cell activation. We have solved the X-ray crystal structures of the three SRCR domains of CD6 and two N-terminal domains of CD166. This first structure of consecutive SRCR domains reveals a nonlinear organization. We characterized the binding sites on CD6 and CD166 and showed that a SNP in CD6 causes glycosylation that hinders the CD6/CD166 interaction. Native mass spectrometry analysis showed that there is competition between the heterophilic and homophilic interactions. These data give insight into how interactions of consecutive SRCR domains are perturbed by SNPs and potential therapeutic reagents. PMID- 26146187 TI - Interaction between the Linker, Pre-S1, and TRP Domains Determines Folding, Assembly, and Trafficking of TRPV Channels. AB - Functional transient receptor potential (TRP) channels result from the assembly of four subunits. Here, we show an interaction between the pre-S1, TRP, and the ankyrin repeat domain (ARD)-S1 linker domains of TRPV1 and TRPV4 that is essential for proper channel assembly. Neutralization of TRPV4 pre-S1 K462 resulted in protein retention in the ER, defective glycosylation and trafficking, and unresponsiveness to TRPV4-activating stimuli. Similar results were obtained with the equivalent mutation in TRPV1 pre-S1. Molecular dynamics simulations revealed that TRPV4-K462 generated an alternating hydrogen network with E745 (TRP box) and D425 (pre-S1 linker), and that K462Q mutation affected subunit folding. Consistently, single TRPV4-E745A or TRPV4-D425A mutations moderately affected TRPV4 biogenesis while double TRPV4-D425A/E745A mutation resumed the TRPV4-K462Q phenotype. Thus, the interaction between pre-S1, TRP, and linker domains is mandatory to generate a structural conformation that allows the contacts between adjacent subunits to promote correct assembly and trafficking to the plasma membrane. PMID- 26146190 TI - Influence of the antimicrobial compound allyl isothiocyanate against the Aspergillus parasiticus growth and its aflatoxins production in pizza crust. AB - Aflatoxins (AFs) are secondary metabolites produced by different species of Aspergillus, such as Aspergillus flavus and Aspergillus parasiticus, which possess mutagenic, teratogenic and carcinogenic activities in humans. In this study, active packaging devices containing allyl isothiocyanate (AITC) or oriental mustard flour (OMF) + water were tested to inhibit the growth of A. parasiticus and AFs production in fresh pizza crust after 30 d. The antimicrobial and anti-aflatoxin activities were compared to a control group (no antimicrobial treatment) and to a group added with commercial preservatives (sorbic acid + sodium propionate). A. parasiticus growth was only inhibited after 30 d by AITC in filter paper at 5 MUL/L and 10 MUL/L, AITC sachet at 5 MUL/L and 10 MUL/L and OMF sachet at 850 mg + 850 MUL of water. However, AFs production was inhibited by all antimicrobial treatments in a dose-dependent manner. More importantly, AITC in a filter paper at 10 MUL/L, AITC sachet at 10 MUL/L, OMF sachet at 850 mg + 850 MUL of water and sorbic acid + sodium propionate at 0.5-2.0 g/Kg completely inhibited AFs formation. The use of AITC in active packaging devices could be a natural alternative to avoid the growth of mycotoxinogenic fungi in refrigerated bakery products in substitution of common commercial preservatives. PMID- 26146191 TI - ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach. AB - The wide application of zinc oxide nanoparticles (ZnO NPs) in cosmetics, paints, biosensors, drug delivery, food packaging and as anticancerous agents has increased the risk of human exposure to these NPs. Earlier in vitro and in vivo studies have demonstrated a cytotoxic and genotoxic potential of ZnO NPs. However, there is paucity of data regarding their immunomodulatory effects. Therefore, the present study was aimed to investigate the immunotoxic potential of ZnO NPs using human monocytic cell line (THP-1) as model to understand the underlying molecular mechanism. A significant (p < 0.01) increase in pro inflammatory cytokines (TNF-alpha and IL-1beta) and reactive oxygen species (ROS) was observed with a concomitant concentration dependent (0.5, 1, 5, 10, 15 and 20 MUg/mL) decrease in the glutathione (GSH) levels as compared to control. The expression levels of mitogen activated protein kinase (MAPK) cascade proteins such as p-ERK1/2, p-p38 and p-JNK were also significantly (p < 0.05, p < 0.01) induced. Also, at the concentration tested, NPs induced DNA damage as assessed by the Comet and micronucleus assays. Our data demonstrated that ZnO NPs induce oxidative and nitrosative stress in human monocytes, leading to increased inflammatory response via activation of redox sensitive NF-kappaB and MAPK signalling pathways. PMID- 26146192 TI - Treatment of Patellar Tendinopathy Refractory to Surgical Management Using Percutaneous Ultrasonic Tenotomy and Platelet-Rich Plasma Injection: A Case Presentation. AB - Chronic proximal patellar tendinopathy is a common condition in sports medicine that may be refractory to nonoperative treatments, including activity modification, medications, and comprehensive rehabilitation. Percutaneous ultrasonic tenotomy is a recently developed technique designed to cut and debride tendinopathic tissue, thus promoting pain relief and functional recovery. We present a case of a collegiate athlete with chronic proximal patellar tendinopathy who was effectively treated with percutaneous ultrasonic tenotomy after not responding to extensive nonoperative treatment, surgical debridement, and platelet-rich plasma injections. Percutaneous ultrasonic tenotomy can be considered as a treatment option in patients presenting with refractory proximal patellar tendinopathy, including those who do not respond to previous operative intervention. PMID- 26146193 TI - Cancer Rehabilitation: Do Functional Gains Relate to 60 Percent Rule Classification or to the Presence of Metastasis? AB - BACKGROUND: Literature supporting the benefits of inpatient rehabilitation for cancer patients is increasing. Many cancer patients, however, do not qualify for inclusion in the Centers for Medicare and Medicaid 60% rule and consequently may not receive services. The benefit of inpatient rehabilitation in this specific cancer group has not been investigated and is the focus of this study. OBJECTIVE: To investigate functional gains made during inpatient rehabilitation by patients impaired by cancer, and to compare the functional gains made during inpatient rehabilitation for patients impaired by cancer in relation to the presence or absence of metastatic disease and compliance or noncompliance with the Medicare 60% rule. SETTING: Freestanding university-affiliated rehabilitation hospital. PARTICIPANTS: A total of 176 adult patients admitted for inpatient rehabilitation due to cancer. METHODS: Retrospective chart review of patients admitted for inpatient rehabilitation with deficits identified related to cancer. MAIN OUTCOME MEASURES: Demographic data including cancer type, presence of metastasis, age, gender, marital status, ethnicity, length of stay (LOS), discharge destination, and transfer to acute care. Functional status including admission and discharge Functional Independence Measure Score (FIM), total, motor, and cognitive FIM gains, total, motor, and cognitive FIM efficiency for the study sample, for patients with and without a diagnosis compliant with the 60% rule and for patients with and without metastatic disease. RESULTS: In all, 176 cases met inclusion criteria. An admission coded diagnosis that was compliant with the 60% rule was present in 97 cases (55.1%). In 153 cases, the presence or absence of metastatic disease was known. Metastatic disease was present in 69 cases (45%). All groups (total sample, metastatic versus nonmetastatic, compliant versus noncompliant) made significant functional gains. Patients with a diagnosis noncompliant with the 60% rule had higher admission total FIM (P = .001), discharge total FIM (P = .014), admission motor FIM (P = .005), admission cognitive FIM (P = .008), and discharge cognitive FIM (P < .001) scores than those with a compliant diagnosis. Patients with metastatic disease had higher admission total FIM (P = .026) and admission (P = .001) and discharge (P = .02) cognitive FIM scores than patients with nonmetastatic disease. There were no significant differences between groups regarding total, motor, or cognitive FIM gains or total motor or cognitive FIM efficiencies. Differences in age, length of stay, and admission motor and discharge FIM scores between groups were related to cancer types and source of impairment. CONCLUSION: Patients with functional limitations resulting from cancer or its treatment made significant functional gains in inpatient rehabilitation. There were no significant differences in functional gains made by those with or without metastatic disease or those compliant versus noncompliant with the 60% rule. The presence of metastatic disease or a diagnosis not compliant with the 60% rule does not preclude cancer patients from making significant functional gains. PMID- 26146194 TI - Kinematic, Cardiopulmonary, and Metabolic Responses of Overweight Runners While Running at Self-Selected and Standardized Speeds. AB - OBJECTIVE: To determine the differences in kinematic, cardiopulmonary, and metabolic responses between overweight and healthy weight runners at a self selected and standard running speed. DESIGN: Comparative descriptive study. SETTING: Tertiary care institution, university-affiliated research laboratory. PARTICIPANTS: Overweight runners (n = 21) were matched with runners of healthy weight (n = 42). METHODS: Participants ran at self-selected and standardized speeds (13.6 km/h). Sagittal plane joint kinematics were captured simultaneously with cardiopulmonary and metabolic measures using a motion capture system and portable gas analyzer, respectively. MAIN OUTCOME MEASUREMENTS: Spatiotemporal parameters (cadence, step width and length, center of gravity displacement, stance time) joint kinematics, oxygen cost, heart rate, ventilation and energy expenditure. RESULTS: At the self-selected speed, overweight individuals ran slower (8.5 +/- 1.3 versus 10.0 +/- 1.6 km/h) and had slower cadence (163 versus 169 steps/min; P < .05). The sagittal plane range of motion (ROM) for flexion extension at the ankle, knee, hip, and anterior pelvic tilt were all less in overweight runners compared to healthy weight runners (all P < .05). At self selected speed and 13.6 km/h, energy expenditure was higher in the overweight runners compared to their healthy weight counterparts (P < .05). At 13.6 km/h, only the frontal hip and pelvis ROM were higher in the overweight versus the healthy weight runners (P < .05), and energy expenditure, net energy cost, and minute ventilation were higher in the overweight runners compared to the healthy weight runners (P < .05). CONCLUSION: At self-selected running speeds, the overweight runners demonstrated gait strategies (less joint ROM, less vertical displacement, and shorter step lengths) that resulted in cardiopulmonary and energetic responses similar to those of healthy weight individuals. PMID- 26146195 TI - Nonlinear population receptive field changes in human area V5/MT+ of healthy subjects with simulated visual field scotomas. AB - There is extensive controversy over whether the adult visual cortex is able to reorganize following visual field loss (scotoma) as a result of retinal or cortical lesions. Functional magnetic resonance imaging (fMRI) methods provide a useful tool to study the aggregate receptive field properties and assess the capacity of the human visual cortex to reorganize following injury. However, these methods are prone to biases near the boundaries of the scotoma. Retinotopic changes resembling reorganization have been observed in the early visual cortex of normal subjects when the visual stimulus is masked to simulate retinal or cortical scotomas. It is not known how the receptive fields of higher visual areas, like hV5/MT+, are affected by partial stimulus deprivation. We measured population receptive field (pRF) responses in human area V5/MT+ of 5 healthy participants under full stimulation and compared them with responses obtained from the same area while masking the left superior quadrant of the visual field ("artificial scotoma" or AS). We found that pRF estimations in area hV5/MT+ are nonlinearly affected by the AS. Specifically, pRF centers shift towards the AS, while the pRF amplitude increases and the pRF size decreases near the AS border. The observed pRF changes do not reflect reorganization but reveal important properties of normal visual processing under different test-stimulus conditions. PMID- 26146196 TI - Region of interest correction factors improve reliability of diffusion imaging measures within and across scanners and field strengths. AB - Diffusion tensor imaging (DTI) measures are commonly used as imaging markers to investigate individual differences in relation to behavioral and health-related characteristics. However, the ability to detect reliable associations in cross sectional or longitudinal studies is limited by the reliability of the diffusion measures. Several studies have examined the reliability of diffusion measures within (i.e. intra-site) and across (i.e. inter-site) scanners with mixed results. Our study compares the test-retest reliability of diffusion measures within and across scanners and field strengths in cognitively normal older adults with a follow-up interval less than 2.25 years. Intra-class correlation (ICC) and coefficient of variation (CoV) of fractional anisotropy (FA) and mean diffusivity (MD) were evaluated in sixteen white matter and twenty-six gray matter bilateral regions. The ICC for intra-site reliability (0.32 to 0.96 for FA and 0.18 to 0.95 for MD in white matter regions; 0.27 to 0.89 for MD and 0.03 to 0.79 for FA in gray matter regions) and inter-site reliability (0.28 to 0.95 for FA in white matter regions, 0.02 to 0.86 for MD in gray matter regions) with longer follow-up intervals were similar to earlier studies using shorter follow-up intervals. The reliability of across field strengths comparisons was lower than intra- and inter site reliabilities. Within and across scanner comparisons showed that diffusion measures were more stable in larger white matter regions (>1500 mm(3)). For gray matter regions, the MD measure showed stability in specific regions and was not dependent on region size. Linear correction factor estimated from cross-sectional or longitudinal data improved the reliability across field strengths. Our findings indicate that investigations relating diffusion measures to external variables must consider variable reliability across the distinct regions of interest and that correction factors can be used to improve consistency of measurement across field strengths. An important result of this work is that inter-scanner and field strength effects can be partially mitigated with linear correction factors specific to regions of interest. These data-driven linear correction techniques can be applied in cross-sectional or longitudinal studies. PMID- 26146197 TI - Effects of language experience and stimulus context on the neural organization and categorical perception of speech. AB - Categorical perception (CP) represents a fundamental process in converting continuous speech acoustics into invariant percepts. Using scalp-recorded event related brain potentials (ERPs), we investigated how tone-language experience and stimulus context influence the CP for lexical tones-pitch patterns used by a majority of the world's languages to signal word meaning. Stimuli were vowel pairs overlaid with a high-level tone (T1) followed by a pitch continuum spanning between dipping (T3) and rising (T2) contours of the Mandarin tonal space. To vary context, T1 either preceded or followed the critical T2/T3 continuum. Behaviorally, native Chinese showed stronger CP as evident by their steeper, more dichotomous psychometric functions and faster identification of linguistic pitch patterns than native English-speaking controls. Stimulus context produced shifts in both groups' categorical boundary but was more exaggerated in native listeners. Analysis of source activity extracted from primary auditory cortex revealed overall stronger neural encoding of tone in Chinese compared to English, indicating experience-dependent plasticity in cortical pitch processing. More critically, "neurometric" functions derived from multidimensional scaling and clustering of source ERPs established: (i) early auditory cortical activity could accurately predict listeners' psychometric speech identification and contextual shifts in the perceptual boundary; (ii) neurometric profiles were organized more categorically in native speakers. Our data show that tone-language experience refines early auditory cortical brain representations so as to supply more faithful templates to neural mechanisms subserving lexical pitch categorization. We infer that contextual influence on the CP for tones is determined by language experience and the frequency of pitch patterns as they occur in listeners' native lexicon. PMID- 26146198 TI - Long Term Outcomes Following Freestyle Stentless Aortic Bioprosthesis Implantation: An Australian Experience. AB - BACKGROUND: The Freestyle stentless bioprosthesis (FSB) has been demonstrated to be a durable prosthesis in the aortic position. We present data following Freestyle implantation for up to 10 years post-operatively and compare this with previously published results. METHODS: A retrospective cohort analysis of 237 patients following FSB implantation occurred at five Australian hospitals. Follow up data included clinical and echocardiographic outcomes. RESULTS: The cohort was 81.4% male with age 63.2+/-13.0 years and was followed for a mean of 2.4+/-2.3 years (range 0-10.9 years, total 569 patient-years). The FSB was implanted as a full aortic root replacement in 87.8% patients. The 30-day all cause mortality was 4.2% (2.0% for elective surgery). Cumulative survival at one, five and 10 years was 91.7+/-1.9%, 82.8+/-3.8% and 56.5+/-10.5%, respectively. Freedom from re-intervention at one, five and 10 years was 99.5+/-0.5%, 91.6+/-3.7% and 72.3+/ 10.5%, respectively. At latest echocardiographic review (mean 2.3+/-2.1 years post-operatively), 92.6% had trivial or no aortic regurgitation. Predictors of post-operative mortality included active endocarditis, acute aortic dissection and peripheral vascular disease. CONCLUSIONS: We report acceptable short and long term outcomes following FSB implantation in a cohort of comparatively younger patients with thoracic aortic disease. The durability of this bioprosthesis in the younger population remains to be confirmed. PMID- 26146199 TI - Recurrent ST Elevation Myocardial Infarction: What is the Aetiology? AB - Coronary artery disease is a leading cause of morbidity and mortality in the western world. Plaque rupture in an atherosclerotic lesion is the most commonly encountered underlying pathophysiology. Spontaneous coronary dissection can have similar presentation, but we as a community of cardiologists may not be aware of uncommon aetiologies, such as vasculitis presenting as ST elevation myocardial infarction (STEMI). Here we present a case report of a lady, who presented with STEMI on three occasions within five days, due to underlying granulomotosis with polyangiitis (GPA). PMID- 26146200 TI - Relationship Between Mean Platelet Volume and Pulmonary Embolism in Patients With Deep Vein Thrombosis. AB - BACKGROUND: Mean platelet volume (MPV) has been demonstrated to be associated with deep vein thrombosis (DVT). However, its role in the prediction of pulmonary embolism (PE), which is a major complication of DVT, is still unclear. Therefore, we investigated the association of MPV values with acute PE in patients with DVT. METHOD: The study included three groups: patients with DVT and PE (n=98); patients with DVT without PE (n=97); and control group (No DVT, No PE, n=98). We also evaluated DVT patients according to the MPV values on admission and categorised them into two groups: MPV<=9.15 fL (n=82) and MPV>9.15 fL (n=113). RESULTS: MPV was significantly higher in all DVT patients than controls (9.3+/ 0.9 fL vs 7.9+/-0.7 fL, p<0.001) and in DVT patients with PE than DVT patients without PE (9.9+/-0.6 fL vs 8.7+/-0.7 fL, p<0.001). The rate of PE was higher in patients with DVT with MPV>9.15 fL than those with MVP<=9.15 fL (75.2% vs 15.9%, p<0.001). The presence of PE in patients with DVT was independently associated with MPV (OR: 22.19, 95%CI: 9.39-53.19, P<0.001). CONCLUSION: Although our findings should be considered within the limitations of the study, they suggest that MPV measures may be elevated in DVT patients and a higher MPV may be associated with PE in patients with DVT. PMID- 26146201 TI - A Review of the Endovascular Management of Thoracic Aortic Pathology. AB - BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has recently gained popularity, but there is ongoing debate surrounding its safety and efficacy. We present 13 years of TEVAR experience at our institution. METHODS: Data from procedures performed between September 2000 and October 2013 were sourced. Eighty one TEVARs were performed in 72 patients for various disorders of the thoracic aorta. RESULTS: The mean duration of follow-up was 62 months (range, 2-140 months). One-month, one-year, and five-year survival rates were 93%, 88%, and 63%, respectively. Five mortalities occurred within 30 days of operation (7%), three of which were related to vascular complications. There were 12 episodes of postoperative endoleak (12.5%). The left subclavian artery was covered without revascularisation in nine cases resulting in two episodes of subclavian steal syndrome and one episode of left arm claudication. Three patients had perioperative strokes, and one patient spinal cord ischaemia. CONCLUSIONS: We demonstrated low rates of reintervention after TEVAR and a low risk of complications, particularly neurological. We therefore advocate an endovascular approach for thoracic pathology involving the aortic arch and descending aorta, particularly in elderly patients. Coverage of the LSCA is often necessary, but where possible, prophylactic revascularisation should be performed. PMID- 26146222 TI - [Annular lipoatrophy of the ankles treated by fat grafting: Case report and review of the literature]. AB - INTRODUCTION: Annular lipoatrophy of the ankles is a rare disease. Eleven cases are described in the literature. CASE REPORT: We report the case of a 10-year-old girl having an annular lipoatrophy of the ankles. The clinical history begins with the appearance of inflammatory infiltrated nodules at the two legs, which have evolved in a few months to a circumferential lipoatrophy of the ankles. Laboratory studies showed a very high antistreptolysin O titer, concluding streptococcal origin of this hypodermitis. After two years of stable lesions, the patient received two sessions of fat injection. RESULT/DISCUSSION: A satisfactory outcome of the adipocyte graft was observed with reconstitution of shapely legs, stable over time. Eleven cases described in the literature are found. It is a pediatric pathology seen predominantly in female children. The evolution towards lipoatrophy is systematic with or without treatment initiated at the inflammatory phase. We first discuss the management of aesthetic sequelae of this disease. CONCLUSION: Fat grafting appears to be a good indication for the treatment of the cosmetic sequelae seen in annular lipoatrophy of the ankles. PMID- 26146223 TI - Diversity of entomopathogenic Hypocreales in soil and phylloplanes of five Mediterranean cropping systems. AB - The diversity of entomopathogenic Hypocreales from the soil and phylloplanes in five Mediterranean cropping systems with different degrees of management [organic olive orchard conventional olive orchard, holm oak reforestation, holm oak dehesa (a multifunctional agro-sylvo-pastoral system), and sunflower plantation] was studied during four seasons. A total of 697 entomopathogenic fungal isolates were obtained from 272 soil samples, 1608 crop phylloplane samples and 1368 weed phylloplane samples. The following nine species were identified: Beauveria amorpha, B. bassiana, B. pseudobassiana, B. varroae, Metarhizium brunneum, M. guizhoense, M. robertsii, Paecilomyces marquandii and lilacinum using EF-1alpha gene sequences. All the fungal entomopathogenic species were found in both the soil and phylloplane samples, with the exception of M. robertsii, which was only isolated from the soil. The species richness, diversity (Shannon-Wiener index) and evenness (Pielou index) were calculated for each cropping system, yielding the following species ranking, which was correlated with the crop management intensity: holm oak reforestation>organic olive orchard>conventional olive orchard>holm oak dehesa>sunflower plantation. The number of fungal species isolated was similar in both phylloplane habitats and dissimilar between the soil and the crop phylloplane habitats. The ISSR analysis revealed high genotypic diversity among the B. bassiana isolates on the neighbourhood scale, and the isolates were clustered according to the habitat. These results suggest that the entomopathogenic Hypocreales in the phylloplane could result from the dispersal of fungal propagules from the soil, which might be their habitat of origin; a few isolates, including EABb 09/28-Fil of Beauveria bassiana, inhabit only the phylloplane. PMID- 26146224 TI - Activity of vegetative insecticidal proteins Vip3Aa58 and Vip3Aa59 of Bacillus thuringiensis against lepidopteran pests. AB - Vegetative insecticidal proteins (Vips) secreted by some isolates of Bacillus thuringiensis show activity against insects and are regarded as insecticides against pests. A number of B. thuringiensis strains harbouring vip3A genes were isolated from different sources and identified by using a PCR based approach. The isolates with the highest insecticidal activity were indicated in screening tests, and their vip genes were cloned and sequenced. The analysis revealed two polymorphic Vip protein forms, which were classified as Vip3Aa58 and Vip3Aa59. After expression of the vip genes, the proteins were isolated and characterized. The activity of both toxins was estimated against economically important lepidopteran pests of woodlands (Dendrolimus pini), orchards (Cydia pomonella) and field crops (Spodoptera exigua). Vip3Aa58 and Vip3Aa59 were highly toxic and their potency surpassed those of many Cry proteins used in commercial bioinsecticides. Vip3Aa59 revealed similar larvicidal activity as Vip3Aa58 against S. exigua and C. pomonella. Despite 98% similarity of amino acid sequences of both proteins, Vip3Aa59 was significantly more active against D. pini. Additionally the effect of proteolytic activation of Vip58Aa and Vip3Aa59 on toxicity of D. pini and S. exigua was studied. Both Vip3Aa proteins did not show any activity against Tenebrio molitor (Coleoptera) larvae. The results suggest that the Vip3Aa58 and Vip3Aa59 toxins might be useful for controlling populations of insect pests of crops and forests. PMID- 26146225 TI - Neoplastic diseases of marine bivalves. AB - Two types of prevalent neoplastic diseases have been described in marine bivalves of commercial interest: disseminated neoplasia (DN) and gonadal neoplasia. The first involves the excessive proliferation of abnormal cells with unknown origin (probably of hemic source in some cases/species), disseminating through the circulatory system and infiltrating the connective tissue of various organs; the second consists of an abnormal proliferation of undifferentiated germinal cells of the gonad. These two types of bivalve neoplasia fit the criteria of malignant tumors: pleomorphic and undifferentiated cells, rapid and invasive growth, abundance of mitotic figures, metastasis and progressive development often resulting in the death of the affected individual. Different causes have been suggested regarding etiology: genetic alterations, virus, retrotranspons, and contaminants, although it could depend on the mollusk species; evidence of horizontal transmission of clonal cancer cells as the cause of DN spreading in clam Mya arenaria populations has been recently reported. In some species and populations, the neoplastic disorders affect only a few individuals, but in others reach high prevalence. Among the diagnostic methods, DN has been detected by histology and cytologic examination of hemolymph, and with developed specific antibodies. Recently, flow cytometry has also been applied, allowing detecting DNA quantity alteration. Several studies reported many genes and pathways critically involved in neoplastic transformation in Mya arenaria, Mytilus spp. and Ostrea edulis. These genetic studies will allow the development of diagnosis by PCR which can be used in biomonitoring studies. PMID- 26146226 TI - Vibrio cholerae pathogen from the freshwater-cultured whiteleg shrimp Penaeus vannamei and control with Bdellovibrio bacteriovorus. AB - Vibriosis has become a major global economic problem in freshwater-farmed whiteleg shrimp (Penaeus vannamei). The prevention and control of vibriosis are now priority research topics. In this study, a pathogenic strain (QH) was isolated from vibriosis-infected freshwater-farmed P. vannamei that resulted in leg yellowing and was identified as a Vibrio cholerae isolate through phylogenetic analysis and the API 32GN system. A phylogenetic tree that was constructed using the neighbor-joining method further confirmed the QH isolate as a V. cholerae strain. A virulent outer membrane protein (ompU) gene was found to be present in the QH isolate, which further confirmed its pathogenicity. In addition, Bdellovibrio bacteriovorus conferred significant protection against V. cholerae: B. bacteriovorus exhibited significant bacteriolytic effects on the V. cholerae pathogen, possessed a wide prey range that included Vibrio pathogens, and displayed a positive protective efficacy against experimental V. cholerae infection in P. vannamei. To the best of our knowledge, this is the first report of the control of shrimp pathogen V. cholerae with B. bacteriovorus. PMID- 26146227 TI - Legislative and regulatory aspects of molluscan health management. AB - The world population is growing quickly and there is a need to make sustainable protein available through an integrated approach that includes marine aquaculture. Seafood is already a highly traded commodity but the production from capture fisheries is rarely sustainable, which makes mollusc culture more important. However, an important constraint to its continued expansion is the potential for trade movements to disseminate pathogens that can cause disease problems and loss of production. Therefore, this review considers legislative and regulatory aspects of molluscan health management that have historically attempted to control the spread of mollusc pathogens. It is argued that the legislation has been slow to react to emerging diseases and the appearance of exotic pathogens in new areas. In addition, illegal trade movements are taken into account and possible future developments related to improvements in areas such as data collection and diagnostic techniques, as well as epidemiology, traceability and risk analysis, are outlined. PMID- 26146228 TI - Development of in situ hybridization and PCR assays for the detection of Enterocytozoon hepatopenaei (EHP), a microsporidian parasite infecting penaeid shrimp. AB - A microsporidian parasite, Enterocytozoon hepatopenaei (abbreviated as EHP), is an emerging pathogen for penaeid shrimp. EHP has been found in several shrimp farming countries in Asia including Vietnam, Thailand, Malaysia, Indonesia and China, and is reported to be associated with growth retardation in farmed shrimp. We examined the histological features from infected shrimp collected from Vietnam and Brunei, these include the presence of basophilic inclusions in the hepatopancreas tubule epithelial cells, in which EHP is found at various developmental stages, ranging from plasmodia to mature spores. By a PCR targeting the 18S rRNA gene, a 1.1kb 18S rRNA gene fragment of EHP was amplified, and this sequence showed a 100% identity to EHP found in Thailand and China. This fragment was cloned and labeled with digoxigenin-11-dUTP, and in situ hybridized to tissue sections of infected Penaeus vannamei (from Vietnam) and P. stylirostris (Brunei). The results of in situ hybridization were specific, the probe only reacted to the EHP within the cytoplasmic inclusions, not to a Pleistophora-like microsporidium that is associated with cotton shrimp disease. Subsequently, we developed a PCR assay from this 18S rRNA gene region, this PCR is shown to be specific to EHP, did not react to 2 other parasitic pathogens, an amoeba and the cotton shrimp disease microsporidium, nor to genomic DNA of various crustaceans including polychaetes, squids, crabs and krill. EHP was detected, through PCR, in hepatopancreatic tissue, feces and water sampled from infected shrimp tanks, and in some samples of Artemia biomass. PMID- 26146229 TI - Paradoxium irvingi n.gen. n.sp. (Microsporidia) infecting the musculature of European pink shrimp Pandalus montagui. AB - This paper utilises histological, ultrastructure and molecular phylogenetic data to describe a novel genus and species (Paradoxium irvingi n.gen., n.sp.) within clade 5 of the phylum Microsporidia. The parasite infects the musculature of the pink shrimp Pandalus montagui captured from United Kingdom waters. The novel microsporidium is morphologically and phylogenetically dissimilar to its nearest phylogenetic branch relative Thelohania butleri infecting the sister shrimp taxon Pandalus jordani. Furthermore, it is morphologically distinct from the type species of the genus Thelohania, Thelohania giardi infecting European brown shrimp Crangon crangon. Since phylogenetic data pertaining to type T. giardi is not currently available, our discovery places some doubt on the likelihood that T. butleri represents the proposed surrogate for the type taxon. Further it demonstrates potential for significant morphological plasticity in this clade of muscle-infecting microsporidians of crustaceans which contains the genera Myospora, Cucumispora, Thelohania, and now Paradoxium. Since it cannot be stated with certainty that T. butleri (or other taxa within the clade) represent true close relatives of T. giardi, clarity on this issue will only occur with re discovery and genotyping of type T. giardi infecting C. crangon from European waters. PMID- 26146230 TI - Metarhizium pingshaense applied as a seed treatment induces fungal infection in larvae of the white grub Anomala cincta. AB - Metarhizium pingshaense has potential as a control agent of the white grub Anomala cincta. We compared its ability to cause infection when applied as a seed treatment or directly to the compost around the plant roots. Although the greatest infection (93%) occured in the direct inoculation treatment, 50% of larvae still became infected by M. pingshaense applied as a seed treatment. The fungus persisted in the compost and also colonised the roots of the developing maize plants endophytically. More research is required but seed treatments with M. pingshaense have potential as cost-effective control options for A. cincta. PMID- 26146231 TI - Differential diagnosis of the honey bee trypanosomatids Crithidia mellificae and Lotmaria passim. AB - Trypanosomatids infecting honey bees have been poorly studied with molecular methods until recently. After the description of Crithidia mellificae (Langridge and McGhee, 1967) it took about forty years until molecular data for honey bee trypanosomatids became available and were used to identify and describe a new trypanosomatid species from honey bees, Lotmaria passim (Evans and Schwarz, 2014). However, an easy method to distinguish them without sequencing is not yet available. Research on the related bumble bee parasites Crithidia bombi and Crithidia expoeki revealed a fragment length polymorphism in the internal transcribed spacer 1 (ITS1), which enabled species discrimination. In search of fragment length polymorphisms for differential diagnostics in honey bee trypanosomatids, we studied honey bee trypanosomatid cell cultures of C. mellificae and L. passim. This research resulted in the identification of fragment length polymorphisms in ITS1 and ITS1-2 markers, which enabled us to develop a diagnostic method to differentiate both honey bee trypanosomatid species without the need for sequencing. However, the amplification success of the ITS1 marker depends probably on the trypanosomatid infection level. Further investigation confirmed that L. passim is the dominant species in Belgium, Japan and Switzerland. We found C. mellificae only rarely in Belgian honey bee samples, but not in honey bee samples from other countries. C. mellificae was also detected in mason bees (Osmia bicornis and Osmia cornuta) besides in honey bees. Further, the characterization and comparison of additional markers from L. passim strain SF (published as C. mellificae strain SF) and a Belgian honey bee sample revealed very low divergence in the 18S rRNA, ITS1-2, 28S rRNA and cytochrome b sequences. Nevertheless, a variable stretch was observed in the gp63 virulence factor. PMID- 26146232 TI - 2-Deoxy-D-glucose-induced hypothermia in anesthetized rats: Lack of forebrain contribution and critical involvement of the rostral raphe/parapyramidal regions of the medulla oblongata. AB - Systemic or central administration of 2-deoxy-d-glucose (2DG), a competitive inhibitor of glucose utilization, induces hypothermia in awake animals and humans. This response is mediated by the central nervous system, though the neural mechanism involved is largely unknown. In this study, I examined possible involvement of the forebrain, which contains the hypothalamic thermoregulatory center, and the medullary rostral raphe/parapyramidal regions (rRPa/PPy), which mediate hypoxia-induced heat-loss responses, in 2DG-induced hypothermia in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. The intravenous injection of 2DG (250mgkg(-1)) elicited an increase in tail skin temperature and decreases in body core temperature and the respiratory exchange ratio, though it did not induce any significant change in the metabolic rate. These results indicate that the hypothermic response was caused by an increase in heat loss, but not by a decrease in heat production and that it was accompanied by a decrease in carbohydrate utilization and/or an increase in lipid utilization as energy substrates. Complete surgical transection of the brainstem between the hypothalamus and the midbrain had no effect on the 2DG-induced hypothermic responses, suggesting that the hindbrain, but not the forebrain, was sufficient for the responses. However, pretreatment of the rRPa/PPy with the GABAA receptor blocker bicuculline methiodide, but not with vehicle saline, greatly attenuated the 2DG-induced responses, suggesting that the 2DG-induced hypothermia was mediated, at least in part, by GABAergic neurons in the hindbrain and activation of GABAA receptors on cutaneous sympathetic premotor neurons in the rRPa/PPy. PMID- 26146233 TI - Sex and estrogen affect the distribution of urocortin-1 immunoreactivity in brainstem autonomic nuclei of the rat. AB - Urocortin-1 (UCN-1), a neuropeptide closely related to the hypothalamic hormone corticotropin-releasing factor, has been associated with stress, feeding behaviors, cardiovascular control, and to exhibit functional gender differences. This study was done to investigate whether estrogen (E; 17beta-estradiol) treatment (9 weeks) altered UCN-1 immunoreactivity in brainstem autonomic nuclei in female Wistar rats. Experiments were done in age matched adult males (controls), females (intact), and ovariectomized (OVX) only and OVX+E (30pg/ml plasma) treated females. All animals received intracerebroventricular injections of colchicine and were then perfused transcardially with Zamboni's fixative. Coronal brainstem sections (40MUm) were cut and processed immunohistochemically for UCN-1. In males, moderate UCN-1 fiber labeling was found in the nucleus of the solitary tract (NTS) and throughout the rostral ventral lateral medulla (RVLM). Additionally, a few UCN-1 immunoreactive neurons were observed in hypoglossal nucleus (XII), facial nucleus (FN) and nucleus ambiguus (Amb). In intact females and OVX+E females, fewer UCN-1 labeled fibers were found within NTS compared to males. In contrast, the RVLM was more densely innervated in the female cases. Furthermore, in both intact and OVX+E females UCN-1 labeled neurons were found not only within Amb, FN and XII, but also within NTS, RVLM and nucleus raphe pallidus (RP). In OVX only animals, moderate to dense UCN-1 fiber labeling was observed in the NTS complex and throughout RVLM compared to males and the other female groups. However, in contrast to all other groups, UCN-1 labeled neurons were found in greater number within Amb, FN, NTS, dorsal motor nucleus of the vagus, XII, RVLM, magnocellular reticular nucleus and RP. These data not only suggest that sex differences exist in the distribution of UCN-1 within brainstem autonomic areas, but that circulating level of E may play an important role with regards to the function of these UCN-1 neurons during stress responses. PMID- 26146234 TI - Combined conservative treatment and lymphatic venous anastomosis for severe lower limb lymphedema with recurrent cellulitis. AB - BACKGROUND: Lymphedema may be treated either conservatively or surgically. Although conservative therapy is the first-line treatment, some patients are refractory to it and repeat severe cellulitis. We usually perform lymphaticovenous anastomosis (LVA) for lymphedema patients, and LVA can reduce the frequency of cellulitis. CASE REPORT: A 67-year-old woman who had undergone a radical hysterectomy, pelvic lymphadenectomy, and postoperative radiotherapy for cervical cancer at the age 50 years. She developed lymphedema in both legs, and high-pressure compression stockings caused lymphorrhea in the groin and thigh, resulting in recurrent episodes of cellulitis. Lymphoscintigraphy revealed dilation of the lymphatic vessels in both legs. Results of an indocyanine green test revealed dermal backflow throughout the lower body. After wearing low pressure stocking, we performed LVA to reduce cellulitis. After confirming the result of LVA, the patients started wearing high-pressure stocking. The patient underwent a subsequent LVA, 3 months after the first, to further improve edema. The lymphorrhea resolved, and cellulitis did not recur. CONCLUSIONS: The combination of surgical treatment and conservative treatment is important for severe lymphedema treatment. Although conservative treatment is usually said to be the first-line treatment, LVA can antecede in cases refractory to conservative treatment. PMID- 26146235 TI - Successful endovascular treatment of duodenal obstruction caused by large abdominal aortic aneurysm. AB - BACKGROUND: Abdominal aortic aneurysm (AAA) causing duodenal obstruction is not a common presentation. Our literature review demonstrated that open surgery was often used to treat such problem. Here, we describe the first case of an endovascular approach to treat acute duodenal obstruction caused by a massive infrarenal AAA. CASE REPORT: An 84-year-old man presented with acute abdominal pain and distension, vomiting, decreasing appetite, and weight loss. Computed tomography scan confirmed a large infrarenal AAA causing duodenal obstruction. The patient was started on total parenteral nutrition, and the aneurysm treated by endovascular aneurysm repair (EVAR). Postoperatively, the patient's symptoms of duodenal obstruction gradually resolved. CONCLUSIONS: EVAR is a viable treatment option for patients presenting with duodenal obstruction caused by AAA. PMID- 26146236 TI - Sclerosing Paragangliomas of the Carotid Body: A Series of a Rare Variant and Review of the Literature. AB - The incidence of carotid body tumors is less than 1 in 30,000. Histologically, they present with a classic pattern of tumor cells arranged in "zellballen" or nests. A new extremely rare sclerosing subtype has been described in the literature with distinct stromal sclerosis and hyalinization, differentiating it from conventional paragangliomata. We present a case series of 3 patients with this rare variant and also discuss the diagnosis and management of carotid body parangliomas. PMID- 26146237 TI - Cancer survivors' receipt of treatment summaries and implications for patient centered communication and quality of care. AB - OBJECTIVE: The Institute of Medicine recommends cancer survivors completing treatment be provided with a treatment summary to facilitate delivery of patient centered survivorship care. However, the relationship between treatment summary receipt and patient-centered communication (PCC) and overall quality of care (QOC) are not well understood. METHODS: Cancer survivors responding to the Health Information National Trends Survey reported treatment summary receipt, QOC, and experiences of six core functions of PCC. Multivariable logistic regression assessed the relationship between treatment summary receipt and PCC. The prevalence of survivors' treatment summary receipt and demographic/clinical characteristics predictive of treatment summary receipt were also assessed. RESULTS: Of 359 respondents with a cancer history, 34.5% reported receiving a treatment summary. Greater treatment burden was associated with increased treatment summary receipt. Treatment summary receipt was associated with higher QOC and more PCC, both overall and for five of the six PCC functions. CONCLUSION: The receipt of cancer treatment summaries may improve PCC and QOC for survivors. PRACTICE IMPLICATIONS: The positive relationship between treatment summary receipt and survivors' PCC experience substantiates continued efforts to provide treatment summaries to survivors transitioning from active treatment to survivorship care. Future research should characterize mechanisms by which treatment summary provision may enhance PCC. PMID- 26146239 TI - Psychometric properties of the Patient Activation Measure-13 among out-patients waiting for mental health treatment: A validation study in Norway. AB - OBJECTIVE: The Patient Activation Measure-13 (PAM-13) has been found useful for assessing patient knowledge, skills and confidence in management of chronic conditions, but the empirical evidence from mental health is sparse. The psychometric properties of PAM in out-patients waiting for treatment in community mental health centers (CMHC) have therefore been examined. METHODS: A total of 290 adults from two CMHC completed PAM. An exploratory factor analysis was conducted with 273 patients. Data at baseline and after 4 weeks were used to analyze test-retest reliability (n=60) and to analyze the sensitivity to change (n=51). RESULTS: The exploratory factor analysis revealed a fit for a two-factor model (Cronbach's alpha was 0.86 and 0.67), and was assessed for a one-factor model (alpha=0.87). The test-retest intraclass correlation coefficient was 0.76. Sensitivity to change was good with a statistically significant activation improvement (p<0.001) on patients receiving a peer co-led-educational intervention (Cohen's d was 0.85). CONCLUSION: PAM has appropriate and acceptable psychometric properties in mental health settings. PRACTICE IMPLICATIONS: Assessing activation before treatment might be useful for scheduling the delivery of mental health services as well as evaluating educational interventions aimed at improving patient engagement in mental health. PMID- 26146238 TI - Disclosure of complementary health approaches among low income and racially diverse safety net patients with diabetes. AB - OBJECTIVE: Patient-provider communication about complementary health approaches can support diabetes self-management by minimizing risk and optimizing care. We sought to identify sociodemographic and communication factors associated with disclosure of complementary health approaches to providers by low-income patients with diabetes. METHODS: We used data from San Francisco Health Plan's SMARTSteps Program, a trial of diabetes self-management support for low-income patients (n=278) through multilingual automated telephone support. Interviews collected use and disclosure of complementary health approaches in the prior month, patient physician language concordance, and quality of communication. RESULTS: Among racially, linguistically diverse participants, half (47.8%) reported using complementary health practices (n=133), of whom 55.3% disclosed use to providers. Age, sex, race/ethnicity, nativity, education, income, and health literacy were not associated with disclosure. In adjusted analyses, disclosure was associated with language concordance (AOR=2.21, 95% CI: 1.05, 4.67), physicians' interpersonal communication scores (AOR=1.50, 95% CI: 1.03, 2.19), shared decision making (AOR=1.74, 95% CI: 1.33, 2.29), and explanatory-type communication (AOR=1.46, 95% CI: 1.03, 2.09). CONCLUSION: Safety net patients with diabetes commonly use complementary health approaches and disclose to providers with higher patient-rated quality of communication. PRACTICE IMPLICATIONS: Patient-provider language concordance and patient-centered communication can facilitate disclosure of complementary health approaches. PMID- 26146240 TI - A pragmatic randomized controlled trial of the Flinders Program of chronic condition management in community health care services. AB - OBJECTIVES: To evaluate the Flinders Program in improving self-management in common chronic conditions. To examine properties of the Partners in Health scale (PIH). METHODS: Participants were randomized to usual care or Flinders Program plus usual care. Self-management competency, quality of life, and other outcomes were measured at baseline, 6 months, and 12 months. RESULTS: Of 231 participants, 172 provided data at 6 months and 61 at 12 months. At 6 months, intention-to treat outcomes favoured the intervention group for SF-12 physical health (p=0.043). Other pre-determined outcomes did not show significance. At 6 months intervention participants' problem severity scores reduced (p<0.001) and goal achievement scores increased (p<0.001). Only 55% of the intervention group received a Flinders Program, compromising study power. The PIH was associated with other measures at baseline and for change over time. CONCLUSION: In a pragmatic community trial, the Flinders Program improved quality of life at 6 months. Incomplete in-practice intervention delivery limited trial power. Studies are now needed on improving delivery. The PIH has potential as a generic risk screening tool and predictive measure of change in self-management and chronic condition outcomes over time. PRACTICE IMPLICATIONS: Better implementation including service integration is required for improved chronic disease management. PMID- 26146276 TI - High maternal serum ferritin in early pregnancy and risk of spontaneous preterm birth. AB - Previous studies have reported inconsistent associations between maternal serum ferritin concentrations and the risk of spontaneous preterm birth (sPTB). The aim of the present study was to examine the association between Fe biomarkers, including serum ferritin concentrations, and the risk of total ( 75th percentile ( >= 43 MUg/l) (OR 1.49, 95% CI 1.06, 2.10) and >90th percentile ( >= 68 MUg/l) (OR 1.92, 95% CI 1.25, 2.96). Increased odds of early and moderate-to-late sPTB were associated with ferritin levels >90th percentile (OR 2.50, 95% CI 1.32, 4.73) and >75th percentile (OR 1.56, 95% CI 1.03, 2.37), respectively. No association was found between the risk of sPTB and elevated sTfR levels or Fe deficiency. In conclusion, elevated maternal serum ferritin levels in early pregnancy are associated with an increased risk of sPTB from 34 weeks of gestation. The usefulness of early pregnancy ferritin levels in identifying women at risk of sPTB warrants further investigation. PMID- 26146314 TI - [Clinical reasoning, for the right care]. PMID- 26146315 TI - [The impact of continuous renal replacement therapy training on nursing competence]. AB - Specific training adapted to the needs of caregivers in intensive care enables professional competence and quality of care to be developed in continuous renal replacement therapy. In addition, it contributes to reducing the stress felt by caregivers and the costs of this technique. PMID- 26146317 TI - [Patients and users of the healthcare system. A patient-caregiver partnership]. PMID- 26146316 TI - [Management of the cutaneous side effects of chemotherapies and targeted therapies]. AB - The treatments used in oncology cause frequent cutaneous side effects. The different types of cutaneous toxicities depend on the class of anti-tumour therapies and can involve the skin, mucosa, nails and hair. Effectively managing these cutaneous toxicities requires adapted preventive and curative measures in order to reduce their impact, notably on patients' quality of life. PMID- 26146318 TI - [From being given a voice to representation, the role of the users in the health care system]. AB - The last thirty years have been marked by the distinct maturing and mobilisation of patient associations, as well as by the recognition of their expertise, enabling them to legitimately interact with public authorities and professionals. However, the representation system, built essentially around the defence of patients' rights, is struggling to implement the cultural changes necessary to ensure organisations and practices evolve towards a real exercising of these rights. PMID- 26146319 TI - [The law of March 4th, 2002 - the Patient's Rights Statute]. AB - With regards to the health professionals-patients relationships, this Statute marked a transition from a system to another : from the "knowing" professional one to the patient-actor one. The rights granted to patients are designed to given them the means to become such a player. PMID- 26146320 TI - [The healthcare democracy]. AB - Thirteen years after the law of 4th March 2002, known as the "Kouchner law", what is the situation regarding the much talked about healthcare democracy? Individual and collective rights have been granted to the users of the health care system. In addition, a series of actions have been promoted in order to exert them. Finally, a number of places and processes favouring consultation have been put in place. PMID- 26146321 TI - [Contemporary transformations of the care relationship]. AB - The occurrence of a disease can sometimes be rather brutal. Care accompanies and takes charge of it, evolving with medicine and society. Human sciences have built the content of the care relationship, with the resulting risk of its instrumentalisation and the belief that patients can be considered within a generalised administration of their lives. PMID- 26146322 TI - [Expert patients and caregivers, towards relationships of reciprocity]. AB - The increased effectiveness of therapies and the changes to the treatment pathways of chronic patients have given rise to new needs for these patients. They require new types of programmes, including training. They show that these patients can produce knowledge and acquire skills which can be useful for the wider community and can be transferred outside the immediate care environment. PMID- 26146323 TI - [The user, a stakeholder in the functioning of the hospital]. AB - The French commission for relations with users and the quality of patient management (CruqPC) is a body which favours, in hospitals, the joint perspective of medical staff, nurses, administrative representatives and users regarding issues relating to the reception of users and the quality and safety of care. Its functioning is however disparate. Its place and its missions need to evolve. PMID- 26146324 TI - [The wishes and autonomy of the patient faced with a care decision]. AB - The evolution of the care relationship, which gives a growing place to the wishes of the patient, poses two sorts of questions to the teams on the clinical wards. How far should they go in order to respect these wishes when the patient's autonomy is diminished? Can the user's free choice be conceived as absolute, or must it be framed by collective rules governing medical practice and the functioning of the institution. Consequently, how can the rights and obligations of the players and users of the healthcare system be articulated? PMID- 26146325 TI - [Disclosing a care-related injury]. AB - Despite an ethical and legal obligation, the information given to patients in the event of a care-related injury is still often poor. It is expected by patients but the situation is difficult for health professionals. In order to be beneficial for all parties, it requires professionals to have a certain amount of expertise and people skills to enable them to empathise and communicate. It should be included in initial and continuing training and in institutions' quality of care policies. PMID- 26146326 TI - [Nurses' knowledge about the health care proxy and advance directives]. AB - The Basse-Normandie palliative care nurses' group carried out a survey regarding nurses' knowledge of the health care proxy and advance directives. The study revealed a lack of connection between these two arrangements, poor knowledge about advance directives but an understanding of the role of the health care proxy. How, therefore, can patients be effectively informed? How should they be supported in this process of determining themselves the conditions of their end of life? PMID- 26146327 TI - [Information as an act of care]. AB - The information process may be conceived as an acte of care. Taking into account its' subjective aspects brings into play the notions of "expertise" and "transparency". The complexity of hematopoietic stem cell transplantation allow analyzing patients' information ethical and clinical issues. PMID- 26146328 TI - [The rights and the role of the patient in the training of nurses]. AB - Seven years after the law of 2002 relating to patients' rights, the decree of 31st July 2009 introduced these rights into nurses' initial training. This has resulted in a few hours of theoretical training and tutorials based on the experience of the first internships. However, the training reference framework contains no mention of the active role which the patient should play in their healthcare pathway. PMID- 26146329 TI - [A new relationship between users and caregivers in the pathway of care]. PMID- 26146330 TI - [Mixed approaches in nursing science]. AB - Mixed methods research uses methodologies from quantitative and qualitative approaches in a single project. Thanks to the integration of the results of the studies, complex phenomena can be explored. The designs are based on specific criteria of rigour. Strategies exist for the design of this type of research. PMID- 26146331 TI - [Delegation of operative duties to nursing staff]. PMID- 26146342 TI - Stereochemical modulation of emission behaviour in E/Z isomers of diphenyldipyrroethene from aggregation induced emission to crystallization induced emission. AB - Herein, we report the synthesis, separation and characterisation of the E- and Z isomers of dipyrrolyldiphenylethene to study their emission behaviour in the aggregation state and solid state. The E-isomer showed pronounced aggregation induced emission (AIE) whereas the Z-isomer showed crystallization induced emission (CIE). The present study explains that the emission behaviour (AIE/CIE) is dependent on the inter/intra molecular interactions between the molecules. The study also confirms that restriction of intramolecular rotation (RIR) is the main cause of AIE/CIE in olefinic luminogens Tetraphenylethylene (TPE) type systems rather than E/Z isomerisation. PMID- 26146343 TI - Isolation and characterization of the [Ga2Al18O8(OH)36(H2O)12](8+) cluster: cationic variations on the Wells-Dawson topology. AB - The structural chemistry of Group 13 polyoxometalates lags far behind related negatively charged transition metal species and limits the development of advanced materials. A novel heterometallic cluster [Ga2Al18O8(OH)36(H2O)12](8+) (Ga2Al18) has been isolated using a supramolecular approach and structurally characterized using single-crystal X-ray diffraction. Ga2Al18 represents the Wells-Dawson structure polycations and variations in the structural topology may be related to the initial stabilization of the Keggin isomer. DFT calculations on the related epsilon-Keggins (GaAl12 and Al13), Ga2Al18, and theoretical Al2Al18 clusters reveal similar features of electronic structure, suggesting additional heteroatom substitution in other isostructural clusters should be possible. PMID- 26146358 TI - De novo synthesis of phenolic dihydroxanthene near-infrared emitting fluorophores. AB - We report a flexible de novo synthesis of phenolic dihydroxanthene fluorophores. The synthesis relies on a one-pot formation of an aldehyde intermediate which can be diversified in 60-70% overall yield, providing an efficient access to this family of near-infrared emitting fluorophores. PMID- 26146359 TI - Deciphering the binding patterns and conformation changes upon the bovine serum albumin-rosmarinic acid complex. AB - Rosmarinic acid (RA) is an importantly and naturally occurring polyphenol from plants of the mint family with potent biological activities. Here, the in vitro interaction of RA with bovine serum albumin (BSA) has been investigated using various biophysical approaches as well as molecular modeling methods, to ascertain its binding mechanism and conformational changes. The fluorescence results demonstrated that the fluorescence quenching of BSA by RA was mainly the result of the formation of a ground state BSA-RA complex, and BSA had one high affinity RA binding site with a binding constant of 4.18 * 10(4) mol L(-1) at 298 K. Analysis of thermodynamic parameters revealed that hydrophobic and hydrogen bond interactions were the dominant intermolecular force in the complex formation. The primary binding site of RA in BSA (site I) had been identified by site marker competitive experiments. The distance between RA and the tryptophan residue of BSA was evaluated at 3.12 nm based on Forster's theory of non radiation energy transfer. The UV-vis absorption, synchronous fluorescence, three dimensional fluorescence, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectra confirmed that the conformation and structure of BSA were altered in the presence of RA. Moreover, the nuclear magnetic spectroscopy showed that the aromatic groups of RA took part in the binding reaction during the BSA-RA complexation. In addition, the molecular picture of the interaction mechanism between BSA and RA at the atomic level was well examined by molecular docking and dynamics studies. In brief, RA can bind to BSA with noncovalent bonds in a relatively stable way, and these findings will be beneficial to the functional food research of RA. PMID- 26146360 TI - The amido-pentadienoate-functionality of the rakicidins is a thiol reactive electrophile--development of a general synthetic strategy. AB - We demonstrate that a unique class-defining functionality (mc-APD) found in macrocyclic natural products with potent anti-cancer activity, imparts these compounds with electrophilic reactivity. The mc-APD group represents an interesting structural hybrid between canonical biologically relevant Michael acceptors. Further, a novel thiol-elimination method for preparation of the mc APD group is outlined. PMID- 26146361 TI - Micro-CT analyses of historical bone samples presenting with osteomyelitis. AB - OBJECTIVE: Osteomyelitis is an inflammation of the bone marrow mainly caused by bacteria such as Staphylococcus aureus. It typically affects long bones, e.g. femora, tibiae and humeri. Recently micro-computed tomography (MUCT) techniques offer the opportunity to investigate bone micro-architecture in great detail. Since there is no information on long bone microstructure in osteomyelitis, we studied historic bone samples with osteomyelitis by MUCT. MATERIALS AND METHODS: We investigated 23 femora of 22 individuals suffering from osteomyelitis provided by the Collection of Anatomical Pathology, Museum of Natural History, Vienna (average age 44 +/-19 years); 9 femora from body donors made available by the Department of Applied Anatomy, Medical University of Vienna (age range, 56-102 years) were studied as controls. Bone microstructure was assessed by MUCT VISCOM X 8060 II with a minimal resolution of 18 MUm. RESULTS: In the osteomyelitic femora, most prominent alterations were seen in the cortical compartment. In 71.4% of the individuals with osteomyelitis, cortical porosity occurred. 57.1% of the individuals showed cortical thinning. In 42.9% trabecularisation of cortical bone was observed. CONCLUSION: Osteomyelitis is associated with severe alterations of cortical bone structure otherwise typically observed at old age such as cortical porosity and cortical thinning. PMID- 26146362 TI - Boosting Photovoltaic Performance of Dye-Sensitized Solar Cells Using Silver Nanoparticle-Decorated N,S-Co-Doped-TiO2 Photoanode. AB - A silver nanoparticle-decorated N,S-co-doped TiO2 nanocomposite was successfully prepared and used as an efficient photoanode in high-performance dye-sensitized solar cells (DSSCs) with N719 dye. The DSSCs assembled with the N,S-TiO2@Ag modified photoanode demonstrated an enhanced solar-to-electrical energy conversion efficiency of 8.22%, which was better than that of a DSSC photoanode composed of unmodified TiO2 (2.57%) under full sunlight illumination (100 mWcm( 2), AM 1.5 G). This enhanced efficiency was mainly attributed to the reduced band gap energy, improved interfacial charge transfer, and retarded charge recombination process. The influence of the Ag content on the overall efficiency was also investigated, and the optimum Ag content with N,S-TiO2 was found to be 20 wt%. Because of the enhanced solar energy conversion efficiency of the N,S TiO2@Ag nanocomposite, it should be considered as a potential photoanode for high performance DSSCs. PMID- 26146363 TI - Efficient AID targeting of switch regions is not sufficient for optimal class switch recombination. AB - Antibody affinity maturation relies on activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) of immunoglobulin (Ig) loci. Class switch recombination (CSR) can in parallel occur between AID-targeted, transcribed, spliced and repetitive switch (S) regions. AID thus initiates not only mutations but also double-strand breaks (DSBs). What governs the choice between those two outcomes remains uncertain. Here we explore whether insertion of transcribed intronic S regions in a locus (Igkappa) strongly recruiting AID is sufficient for efficient CSR. Although strongly targeted by AID and carrying internal deletions, the knocked-in S regions only undergo rare CSR-like events. This model confirms S regions as exquisite SHM targets, extending AID activity far from transcription initiation sites, and shows that such spliced and repetitive AID targets are not sufficient by themselves for CSR. Beyond transcription and AID recruitment, additional IgH elements are thus needed for CSR, restricting this hazardous gene remodelling to IgH loci. PMID- 26146364 TI - Vibronic energy relaxation approach highlighting deactivation pathways in carotenoids. AB - Energy relaxation between two electronic states of a molecule is mediated by a set of relevant vibrational states. We describe this fundamental process in a fully quantum mechanical framework based on first principles. This approach explains population transfer rates as well as describes the entire transient absorption signal as vibronic transitions between electronic states. By applying this vibronic energy relaxation approach to carotenoids, we show that beta carotene's transient absorption signal can be understood without invoking the intensely debated S* electronic state. For a carotenoid with longer chain length, we find that vibronic energy relaxation does not suffice to explain all features in the transient absorption spectra, which we relate to an increased ground state structural inhomogeneity. Our modeling approach is generally applicable to photophysical deactivation processes in molecules. As such, it represents a well founded alternative to data fitting techniques such as global target analysis. PMID- 26146366 TI - Asymmetric zinc porphyrin-sensitized nanosized TiO2 for efficient visible-light driven CO2 photoreduction to CO/CH4. AB - Asymmetric zinc porphyrin (ZnPy) was synthesized and used to sensitize nanosized TiO2. The visible-light-driven activity of CO2 photoreduction to generate CO/CH4 in the gas phase was observed from the ZnPy-sensitized TiO2 without loading noble metal, and the mechanism was discussed. PMID- 26146365 TI - Synergistic activity of polarised osteoblasts inside condensations cause their differentiation. AB - Condensation of pre-osteogenic, or pre-chondrogenic, cells is the first of a series of processes that initiate skeletal development. We present a validated, novel, three-dimensional agent-based model of in vitro intramembranous osteogenic condensation. The model, informed by system heterogeneity and relying on an interaction-reliant strategy, is shown to be sensitive to 'rules' capturing condensation growth and can be employed to track activity of individual cells to observe their macroscopic impact. It, therefore, makes available previously inaccessible data, offering new insights and providing a new context for exploring the emergence, as well as normal and abnormal development, of osteogenic structures. Of the several stages of condensation we investigate osteoblast 'burial' within the osteoid they deposit. The mechanisms underlying entrapment--required for osteoblasts to differentiate into osteocytes--remain a matter of conjecture with several hypotheses claiming to capture this important transition. Computational examination of this transition indicates that osteoblasts neither turn off nor slow down their matrix secreting genes--a widely held view; nor do they secrete matrix randomly. The model further reveals that osteoblasts display polarised behaviour to deposit osteoid. This is both an important addition to our understanding of condensation and an important validation of the model's utility. PMID- 26146367 TI - Assignment of high-lying bending mode levels in the threshold photoelectron spectrum of NH2: a comparison between pyrolysis and fluorine-atom abstraction radical sources. AB - In this manuscript we present threshold photoelectron spectra (TPES) of the amidogen radical, NH2, recorded at two vacuum ultraviolet synchrotron radiation beamlines, the DESIRS beamline of Synchrotron SOLEIL and the VUV beamline of the Swiss Light Source (SLS). Amidogen radicals were generated by two different methods, (a) H-atom abstraction of ammonia in a fluorine microwave discharge flow tube and (b) flash pyrolysis of methylhydrazine and diphenylmethylamine. Due to the large geometry change upon photoionization from the bent neutral molecule NH2 (X[combining tilde] (2)B1) to the quasi-linear cation NH2(+) (X[combining tilde] (3)B1), significant activity in the bending vibration upsilon2(+) of NH2(+) (X[combining tilde] (3)B1) is observed in the TPES. Transitions into a large number of upsilon2(+), Ka(+) levels of the cation are resolved. PMID- 26146368 TI - Palladium(0)-mediated C-H bond activation of N-(naphthyl)salicylaldimine and related ligands: utilization of the resulting organopalladium complexes in catalytic C-C and C-N coupling reactions. AB - N-(Naphthyl)-4-R-salicylaldimines (R = OCH(3), H and Cl; H(2L)(1)-H(2)L(3)) and 2 hydroxy-N-(naphthyl)naphthaldimine (H(2)L(4)) readily undergo, upon reaction with Na(2)[PdCl(4)] in the presence of triphenylphosphine, cyclopalladation via C-H bond activation at the peri-position to afford complexes of type [Pd(L)(PPh(3))] (L = L(1)-L(4)). The C-H bond activation has been found to be mediated by palladium(0) formed in situ. A similar reaction of H(2)L(1) with Na(2)[PdCl(4)] in the presence of 1,2-bis(diphenylphosphino)ethane (dppe), in a 2 : 2 : 1 mole ratio, yields a dinuclear complex of type [{Pd(L(1))}(2)(dppe)]. Reaction of H(2)L(1) with Na(2)[PdCl(4)] in the presence of 4-picoline (pic) yields [Pd(L(1))(pic)]. The molecular structures of the six complexes have been determined by X-ray crystallography. The aldiminate ligand in each compound is coordinated to the metal center as a di-anionic tridentate ONC-donor, with the fourth coordination site occupied by a phosphine or picoline ligand. The new complexes show intense absorptions in the visible and ultraviolet regions, and the nature of the optical transitions has been analyzed by TDDFT calculations. The palladium complexes display notable efficiency in catalyzing C-C and C-N bond coupling reactions. The thermodynamics for the formation of the cyclometalated catalyst precursor [Pd(L(2))(PPh(3))] has been evaluated by DFT calculations. PMID- 26146369 TI - Gas Sensing Properties of Epitaxial LaBaCo2O5.5+delta Thin Films. AB - Chemical reactivity and stability of highly epitaxial mixed-conductive LaBaCo2O5.5+delta (LBCO) thin films on (001) LaAlO3 (LAO) single-crystalline substrates, fabricated by using pulsed laser deposition system, were systematically investigated. Microstructure studies from x-ray diffraction indicate that the films are c-axis oriented with the interface relationship of [100]LBCO//[100]LAO and (001)LBCO//(001)LAO. LBCO thin films can detect the ethanol vapor concentration as low as 10 ppm and the response of LBCO thin film to various ethanol vapor concentrations is very reliable and reproducible with the switch between air and ethanol vapor. Moreover, the fast response of the LBCO thin film, as the p-type gas sensor, is better than some n-type oxide semiconductor thin films and comparable with some nanorods and nanowires. These findings indicate that the LBCO thin films have great potential for the development of gas sensors in reducing/oxidizing environments. PMID- 26146370 TI - A new online exhaust gas monitoring system in hydrochloric acid regeneration of cold rolling mills. AB - Measuring the content of hydrogen chloride (HCl) in exhaust gas used to take time and energy. In this paper, we introduce a new online monitoring system which can output real-time data to the monitoring center. The system samples and cools exhaust gas, and after a series of processing, it will be analyzed by a specific instrument. The core part of this system is remote terminal unit (RTU) which is designed on Cortex-A8 embedded architecture. RTU runs a scaled-down version of Linux which is a good choice of OS for embedded applications. It controls the whole processes, does data acquisition and data analysis, and communicates with monitoring center through Ethernet. In addition, through a software developed for windows, the monitoring process can be remotely controlled. The new system is quite beneficial for steel industry to do environment monitoring. PMID- 26146371 TI - An endophytic bacterium Acinetobacter calcoaceticus Sasm3-enhanced phytoremediation of nitrate-cadmium compound polluted soil by intercropping Sedum alfredii with oilseed rape. AB - Intensive agricultural system with high input of fertilizer results in high agricultural output. However, excessive fertilization in intensive agricultural system has great potential to cause nitrate and heavy metal accumulation in soil, which is adverse to human health. The main objective of the present study was to observe the effects of intercropping and inoculation of endophytic bacterium Acinetobacter calcoaceticus Sasm3 on phytoremediation of combined contaminated soil in oilseed rape (Brassica napus L.). The results showed that with Sasm3 inoculation, the biomass of rape was increased by 10-20% for shoot, 64% for root, and 23-29% for seeds while the nitrate accumulation in rape was decreased by 14% in root and by 12% in shoot. The cadmium concentration in rape increased significantly with mono-inoculating treatment, whereas it decreased significantly after intercropping treatment. By denaturing gradient gel electrophoresis (DGGE) and real-time quantitative PCR analysis, the diversity of bacterial community and the number of nirS and nirK gene copies increased significantly with inoculation or/and intercropping treatment. In conclusion, the endophytic bacterium Sasm3 inoculated intercropping system not only improved the efficiency of clearing cadmium from soil without obstructing crop production, but also improved the quality of crop. PMID- 26146372 TI - Biosurfactant production by Pseudomonas aeruginosa DSVP20 isolated from petroleum hydrocarbon-contaminated soil and its physicochemical characterization. AB - Among 348 microbial strains isolated from petroleum hydrocarbon-contaminated soil, five were selected for their ability to produce biosurfactant based on battery of screening assay including hemolytic activity, surface tension reduction, drop collapse assay, emulsification activity, and cell surface hydrophobicity studies. Of these, bacterial isolate DSVP20 was identified as Pseudomonas aeruginosa (NCBI GenBank accession no. GQ865644) based on biochemical characterization and the 16S rDNA analysis, and it was found to be a potential candidate for biosurfactant production. Maximum biosurfactant production recorded by P. aeruginosa DSVP20 was 6.7 g/l after 72 h at 150 rpm and at a temperature of 30 degrees C. Chromatographic analysis and high-performance liquid chromatography-mass spectrometry (HPLC-MS) revealed that it was a glycolipid in nature which was further confirmed by nuclear magnetic resonance (NMR) spectroscopy. Bioremediation studies using purified biosurfactant showed that P. aeruginosa DSVP20 has the ability to degrade eicosane (97%), pristane (75%), and fluoranthene (47%) when studied at different time intervals for a total of 7 days. The results of this study showed that the P. aeruginosa DSVP20 and/or biosurfactant produced by this isolate have the potential role in bioremediation of petroleum hydrocarbon-contaminated soil. PMID- 26146374 TI - Cadmium, lead, and zinc mobility and plant uptake in a mine soil amended with sugarcane straw biochar. AB - Accumulation of heavy metals in unconsolidated soils can prove toxic to proximal environments, if measures are not taken to stabilize soils. One way to minimize the toxicity of metals in soils is the use of materials capable of immobilizing these contaminants by sorption. Biochar (BC) can retain large amounts of heavy metals due to, among other characteristics, its large surface area. In the current experiment, sugarcane-straw-derived biochar, produced at 700 degrees C, was applied to a heavy-metal-contaminated mine soil at 1.5, 3.0, and 5.0% (w/w). Jack bean and Mucuna aterrima were grown in pots containing a mine contaminated soil and soil mixed with BC. Pore water was sampled to assess the effects of biochar on zinc solubility, while soils were analyzed by DTPA extraction to confirm available metal concentrations. The application of BC decreased the available concentrations of Cd, Pb, and Zn in the mine contaminated soil leading to a consistent reduction in the concentration of Zn in the pore water. Amendment with BC reduced plant uptake of Cd, Pb, and Zn with the jack bean uptaking higher amounts of Cd and Pb than M. aterrima. This study indicates that biochar application during mine soil remediation could reduce plant concentrations of heavy metals. Coupled with this, symptoms of heavy metal toxicity were absent only in plants growing in pots amended with biochar. The reduction in metal bioavailability and other modifications to the substrate induced by the application of biochar may be beneficial to the establishment of a green cover on top of mine soil to aid remediation and reduce risks. PMID- 26146373 TI - Microbial community structure and dynamics in a membrane bioreactor supplemented with the flame retardant dibromoneopentyl glycol. AB - Brominated flame retardants (BFRs) are a group of widely used compounds that, due to their limited biodegradability, exhibit excessive persistence in the environment. The persistence and high toxicity of these compounds to the natural biota causes great environmental concern. We investigated the biodegradation of the BFR dibromoneopentyl glycol (DBNPG) under continuous culture conditions using a miniature membrane bioreactor (mMBR) to assess its feasibility as a bioremediation approach. This system demonstrated long-term, stable biodegradation of DBNPG (>90 days), with an average removal rate of about 50%. Pyrosequencing of the 16S rRNA gene of the microorganisms involved in this process revealed the dominance of reads affiliated with the genus Brevundimonas of the Alphaproteobacteria class during the different mMBR operational stages. The bacterial community was also dominated by reads affiliated with the Sinorhizobium and Sphingopyxis genera within the Alphaproteobacteria class and the Sediminibacterium genus of the Sphingobacteria class. Real-time PCR used to analyze possible changes in the population dynamics of these four dominant groups revealed their consistent presence throughout the long-term mMBR biodegradation activity. Two genera, Brevundimonas and Sphingopyxis, were found to increase in abundance during the acclimation period and then remained relatively stable, forming the main parts of the consortium over the prolonged active stage. PMID- 26146386 TI - A three-dimensional metal-organic polymer: poly[bis(MU2-pyrimidine-2-thiolato kappa4N1,S:S,N3)lead(II)]. AB - The title compound, [Pb(C4H3N2S)2]n, was prepared by the reaction of [Pb(OAc)2].3H2O (OAc is acetate) with pyrimidine-2-thione in the presence of triethylamine in methanol. In the crystal structure, the Pb(II) atom has an N4S4 coordination environment with four ligands coordinated by N- and S-donor atoms. This compound shows that the pyrimidine-2-thiolate anion can lead to a three dimensional network when the coordination number of the metal ion can be higher than 6, as is the case with the Pb(II) ion. This compound presents only covalent bonds, showing that despite the possibility of the hemidirected geometries of Pb(II), the eight-coordinated ion does not allow the formation of an isolated molecular structure with pyrimidine-2-thiolate as the ligand. PMID- 26146385 TI - Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. AB - Damaged mitochondria are removed by mitophagy. Although Atg32 is essential for mitophagy in yeast, no Atg32 homologue has been identified in mammalian cells. Here, we show that Bcl-2-like protein 13 (Bcl2-L-13) induces mitochondrial fragmentation and mitophagy in mammalian cells. First, we hypothesized that unidentified mammalian mitophagy receptors would share molecular features of Atg32. By screening the public protein database for Atg32 homologues, we identify Bcl2-L-13. Bcl2-L-13 binds to LC3 through the WXXI motif and induces mitochondrial fragmentation and mitophagy in HEK293 cells. In Bcl2-L-13, the BH domains are important for the fragmentation, while the WXXI motif facilitates mitophagy. Bcl2-L-13 induces mitochondrial fragmentation in the absence of Drp1, while it induces mitophagy in Parkin-deficient cells. Knockdown of Bcl2-L-13 attenuates mitochondrial damage-induced fragmentation and mitophagy. Bcl2-L-13 induces mitophagy in Atg32-deficient yeast cells. Induction and/or phosphorylation of Bcl2-L-13 may regulate its activity. Our findings offer insights into mitochondrial quality control in mammalian cells. PMID- 26146387 TI - A two-dimensional ZnII coordination polymer constructed from benzene-1,2,3 tricarboxylic acid and N,N'-bis[(pyridin-4-yl)methylidene]hydrazine. AB - The hydrothermal synthesis of the novel complex poly[aqua(MU4-benzene-1,2,3 tricarboxylato)[MU2-4,4'-(hydrazine-1,2 diylidenedimethanylylidene)dipyridine](MU3-hydroxido)dizinc(II)], [Zn(C9H3O6)(OH)(C12H10N4)(H2O)]n, is described. The benzene-1,2,3-tricarboxylate ligand connects neighbouring Zn4(OH)2 secondary building units (SBUs) producing an infinite one-dimensional chain. Adjacent one-dimensional chains are connected by the N,N'-bis[(pyridin-4-yl)methylidene]hydrazine ligand, forming a two dimensional layered structure. Adjacent layers are stacked to generate a three dimensional supramolecular architecture via O-H...O hydrogen-bond interactions. The thermal stability of this complex is described and the complex also appears to have potential for application as a luminescent material. PMID- 26146388 TI - Structural studies of (prop-2-en-1-yl)bis[(pyridin-2-yl)methylidene]amine hetero scorpionate copper complexes. AB - The structures of five compounds consisting of (prop-2-en-1-yl)bis[(pyridin-2 yl)methylidene]amine complexed with copper in both the Cu(I) and Cu(II) oxidation states are presented, namely chlorido{(prop-2-en-1-yl)bis[(pyridin-2 yl)methylidene]amine-kappa(3)N,N',N''}copper(I) 0.18-hydrate, [CuCl(C15H17N3)].0.18H2O, (1), catena-poly[[copper(I)-MU2-(prop-2-en-1 yl)bis[(pyridin-2-yl)methylidene]amine-kappa(5)N,N',N'':C(2),C(3)] perchlorate acetonitrile monosolvate], {[Cu(C15H17N3)]ClO4.CH3CN}n, (2), dichlorido{(prop-2 en-1-yl)bis[(pyridin-2-yl)methylidene]amine-kappa(3)N,N',N''}copper(II) dichloromethane monosolvate, [CuCl2(C15H17N3)].CH2Cl2, (3), chlorido{(prop-2-en-1 yl)bis[(pyridin-2-yl)methylidene]amine-kappa(3)N,N',N''}copper(II) perchlorate, [CuCl(C15H17N3)]ClO4, (4), and di-MU-chlorido-bis({(prop-2-en-1-yl)bis[(pyridin-2 yl)methylidene]amine-kappa(3)N,N',N''}copper(II)) bis(tetraphenylborate), [Cu2Cl2(C15H17N3)2][(C6H5)4B]2, (5). Systematic variation of the anion from a coordinating chloride to a noncoordinating perchlorate for two Cu(I) complexes results in either a discrete molecular species, as in (1), or a one-dimensional chain structure, as in (2). In complex (1), there are two crystallographically independent molecules in the asymmetric unit. Complex (2) consists of the Cu(I) atom coordinated by the amine and pyridyl N atoms of one ligand and by the vinyl moiety of another unit related by the crystallographic screw axis, yielding a one dimensional chain parallel to the crystallographic b axis. Three complexes with Cu(II) show that varying the anion composition from two chlorides, to a chloride and a perchlorate to a chloride and a tetraphenylborate results in discrete molecular species, as in (3) and (4), or a bridged bis-MU-chlorido complex, as in (5). Complex (3) shows two strongly bound Cl atoms, while complex (4) has one strongly bound Cl atom and a weaker coordination by one perchlorate O atom. The large noncoordinating tetraphenylborate anion in complex (5) results in the core bridged Cu2Cl2 moiety. PMID- 26146389 TI - A three-dimensional CdII coordination polymer constructed from 1,1'-biphenyl 2,2',5,5'-tetracarboxylate and 1,4-bis(1H-imidazol-1-yl)benzene ligands. AB - The title coordination polymer, poly[[aqua(MU5-1,1'-biphenyl-2,2',5,5' tetracarboxylato)bis[MU2-1,4-bis(1H-imidazol-1-yl)benzene]dicadmium(II)] dihydrate], {[Cd2(C16H6O8)(C12H10N4)2(H2O)].2H2O}n, was crystallized from a mixture of 1,1'-biphenyl-2,2',5,5'-tetracarboxylic acid (H4bpta), 1,4-bis(1H imidazol-1-yl)benzene (1,4-bib) and cadmium nitrate in water-dimethylformamide. The crystal structure consists of two crystallographically independent Cd(II) cations, with one of the Cd(II) cations possessing a slightly distorted pentagonal bipyramidal geometry. The second Cd(II) centre is coordinated by carboxylate O atoms and imidazole N atoms from two separate 1,4-bib ligands, displaying a distorted octahedral CdN2O4 geometry. The completely deprotonated bpta(4-) ligand, exhibiting a new coordination mode, bridges five Cd(II) cations to form one-dimensional chains via MU3-eta(1):eta(2):eta(1):eta(2) and MU2 eta(1):eta(1):eta(0):eta(0) modes, and these are further linked by 1,4-bib ligands to form a three-dimensional framework with a (4(2).6(4))(4.6(2))(4(3).6(5).7(2)) topology. The structure of the coordination polymer is reinforced by intermolecular hydrogen bonding between carboxylate O atoms, aqua ligands and crystallization water molecules. The solid-state photoluminescence properties were investigated and the complex might be a candidate for a thermally stable and solvent-resistant blue fluorescent material. PMID- 26146390 TI - Structures of CoII and ZnII complexes of the proton-transfer compound derived from pyrazine-2,3-dicarboxylic acid and piperazine. AB - The reaction of the proton-transfer compound piperazine-1,4-diium pyrazine-2,3 dicarboxylate 4.5-hydrate, C4H12N2(2+).C6H2N2O4(2-).4.5H2O or (pipzH2)(pyzdc).4.5H2O (pyzdcH2 is pyrazine-2,3-dicarboxylic acid and pipz is piperazine), (I), with Zn(NO3)2.6H2O and CoCl2.6H2O results in the formation of bis(piperazine-1,4-diium) bis(MU-pyrazine-2,3-dicarboxylato) kappa(3)N(1),O(2):O(3);kappa(3)O(3):N(1),O(2)-bis[aqua(pyrazine-2,3-dicarboxylato kappa(2)N(1),O(2))zinc(II)] decahydrate, (C4H12N2)2[Zn2(C6H2N2O4)4(H2O)2].10H2O or (pipzH2)2[Zn(pyzdc)2(H2O)]2.10H2O, (II), and catena-poly[piperazine-1,4-diium [cobalt(II)-bis(MU-pyrazine-2,3-dicarboxylato) kappa(3)N(1),O(2):O(3);kappa(3)O(3):N(1),O(2)] hexahydrate], {(C4H12N2)[Co(C6H2N2O4)2].6H2O}n or {(pipzH2)[Co(pyzdc)2].6H2O}n, (III), respectively. In (I), pyzdcH2 is doubly deprotonated on reaction with piperazine as a base. Compound (II) crystallizes as a dimer, whereas compound (III) exists as a one-dimensional coordination polymer. In (II), two pyzdc(2-) groups chelate to each of the two Zn(II) atoms through a ring N atom and an O atom of the 2 carboxylate group. In one ligand, the adjacent 3-carboxylate group bridges to a neighbouring metal atom. A water molecule ligates in the sixth coordination site. The structure of (II) can be described as a commensurate superlattice due to an ordering in the hydrogen-bonded network. In (III), no water is coordinated to the metal atom and the coordination sphere is comprised of two N,O-chelates plus two bridging O atoms. A large number of hydrogen bonds are observed in all three compounds. These interactions, as well as pi-pi and C=O...pi stacking interactions, play important structural roles. PMID- 26146391 TI - Structural study of a manganese(II) 'picket-fence' porphyrin complex. AB - 'Picket-fence' porphyrin compounds are used in the investigation of interactions of hemes with dioxygen, carbon monoxide, nitric monoxide and imidazole ligands. (Cryptand-222)potassium chlorido[meso-tetra(alpha,alpha,alpha,alpha-o pivalamidophenyl)porphyrinato]manganese tetrahydrofuran monosolvate (cryptand-222 is 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane), [K(C18H36N2O6)][Mn(C64H64N8O4)Cl].C4H8O or [K(222)][Mn(TpivPP)Cl].THF [systematic name for TpivPP: 5,10,15,20-tetrakis(2-tert-butanamidophenyl)porphyrin], is a five-coordinate high-spin manganese(II) picket-fence porphyrin complex. It crystallizes with a potassium cation chelated inside a cryptand-222 molecule; the average K-O and K-N distances are 2.83 (4) and 2.995 (13) A, respectively. All four protecting tert-butyl pickets of the porphyrin are ordered. The porphyrin plane is nearly planar, as indicated by the atomic displacements and the dihedral angles between the mean planes of the pyrrole rings and the 24-atom mean plane. The axial chloride ligand is located inside the molecular cavity on the hindered porphyrin side and the Mn-Cl bond is tilted slightly off the normal to the porphyrin plane by 3.68 (2) degrees . The out-of-plane displacement of the metal centre relative to the 24-atom mean plane (Delta24) is 0.7013 (4) A, indicating a noticeable porphyrin core doming. PMID- 26146393 TI - Experimental and theoretical studies of the products of addition-elimination reactions between benzil dihydrazone and three isomeric chlorobenzaldehydes. AB - A series of mono- and di-Schiff bases formed between benzil dihydrazone {BDH; systematic name: (1Z)-[(2E)-2-hydrazinylidene-1,2-diphenylethylidene]hydrazine} and three isomeric chlorobenzaldehydes were designed and synthesized to be used as model compounds to help to explain the reaction mechanisms for the formation of Schiff bases. These compounds are 1-(2-chlorobenzylidene)-2-{2-[2-(2 chlorobenzylidene)hydrazin-1-ylidene]-1,2-diphenylethylidene}hydrazine (BDHOCB), and the 3-chloro (BDHMCB) and 4-chloro (BDHPCB) analogues, all having the formula C28H20Cl2N4. Surprisingly, only di-Schiff bases were obtained; our attempts to push the reaction in favour of the mono-Schiff bases all failed. Density functional theory (DFT) calculations were performed to explain the trend in the experimental results. In the case of the systems studied, the type of Schiff base produced exhibits a clear dependence on the HOMO-LUMO energy gaps (DeltaE(HOMO LUMO)), i.e. the product is mainly governed by its stability. The compounds were characterized by single-crystal X-ray diffractometry, elemental analysis, melting point, (1)H NMR and (13)C NMR spectroscopy. The structural features of the three new Schiff bases are similar. For instance, they have the same chemical formula, all the molecules have a symmetrical double helix structure, with each Ph-C=N-N=C Ph arm exhibiting an anti conformation, and their supramolecular interactions include intermolecular pi-pi and weak C-H...pi stacking interactions. The crystal systems are different, however, viz. triclinic (space group P1-) for BDHPCB, monoclinic (space group P2(1)/n) for BDHOCB and orthorhombic (space group Pnna) for BDHMCB. PMID- 26146392 TI - A one-dimensional CdII coordination polymer constructed from 4 (dimethylamino)pyridinium-1-acetate ligands and thiocyanate coordination bridges. AB - A new cadmium-thiocyanate complex, namely catena-poly[1-carboxymethyl-4 (dimethylamino)pyridinium [cadmium(II)-tri-MU-thiocyanato kappa(4)N:S;kappa(2)S:N] [[[4-(dimethylamino)pyridinium-1-acetate kappa(2)O,O']cadmium(II)]-di-MU-thiocyanato-kappa(2)N:S;kappa(2)S:N]], {(C9H13N2O2)[Cd(NCS)3][Cd(NCS)2(C9H12N2O2)]}n, was synthesized by the reaction of 4-(dimethylamino)pyridinium-1-acetate, cadmium nitrate tetrahydrate and potassium thiocyanide in aqueous solution. In the crystal structure, two types of Cd(II) atoms are observed in distorted octahedral coordination environments. One type of Cd(II) atom is coordinated by two O atoms from the carboxylate group of the 4 (dimethylamino)pyridinium-1-acetate ligand and by two N atoms and two S atoms from four different thiocyanate ligands, while the second type of Cd(II) atom is coordinated by three N atoms and three S atoms from six different thiocyanate ligands. Neighbouring Cd(II) atoms are linked by thiocyanate bridges to form a one-dimensional zigzag chain and a one-dimensional coordination polymer. Hydrogen bond interactions are involved in the formation of the supramolecular network. PMID- 26146394 TI - 1-(7-chloro-1,4-dihydroquinolin-4-ylidene)thiosemicarbazide and its hydrochloride: evidence for the existence of a stable imine tautomer in the solid state of 4-aminoquinoline free bases, an anomalous case in nitrogen heterocycles. AB - In the solid state, crystals of both 1-(7-chloro-1,4-dihydroquinolin-4 ylidene)thiosemicarbazide-methanol-water (2/1/1), 2C10H9ClN4S.CH3OH.H2O, (I), and its hydrochloride salt {systematic name: [(7-chloro-1,4-dihydroquinolin-4 ylidene)azaniumyl]thiourea chloride}, C10H10ClN4S(+).Cl(-), (II), assume the imine tautomeric form, contrary to other 4-amino-7-chloroquinolines. Of particular interest are the N-C bond lengths, which have appreciable double-bond character, and the C-N-C aromatic ring bond angle. Both of these parameters have been studied extensively in 4-amino-substituted quinolines. The crystal structures of (I) and (II) in this study provide interesting examples of the amino-imino tautomerism which exists in this class of compound and is, to the best of our knowledge, hitherto unreported. PMID- 26146395 TI - Synthesis, structure and characterization of two copper(II) supramolecular coordination polymers based on a multifunctional ligand 2-amino-4-sulfobenzoic acid. AB - Copper(II) coordination polymers have attracted considerable interest due to their catalytic, adsorption, luminescence and magnetic properties. The reactions of copper(II) with 2-amino-4-sulfobenzoic acid (H(2)asba) in the presence/absence of the auxiliary chelating ligand 1,10-phenanthroline (phen) under ambient conditions yielded two supramolecular coordination polymers, namely (3-amino-4 carboxybenzene-1-sulfonato-kappaO(1))bis(1,10-phenanthroline kappa(2)N,N')copper(II) 3-amino-4-carboxybenzene-1-sulfonate monohydrate, [Cu(C7H6N2O5S)(C12H8N2)2](C7H6N2O5S).H2O, (1), and catena-poly[[diaquacopper(II)] MU-3-amino-4-carboxylatobenzene-1-sulfonato-kappa(2)O(4):O(4')], [Cu(C7H6N2O5S)(H2O)2]n, (2). The products were characterized by FT-IR spectroscopy, thermogravimetric analysis (TGA), solid-state UV-Vis spectroscopy and single-crystal X-ray diffraction analysis, as well as by variable-temperature powder X-ray diffraction analysis (VT-PXRD). Intermolecular pi-pi stacking interactions in (1) link the mononuclear copper(II) cation units into a supramolecular polymeric chain, which is further extended into a supramolecular double chain through interchain hydrogen bonds. Supramolecular double chains are then extended into a two-dimensional supramolecular double layer through hydrogen bonds between the lattice Hasba(-) anions, H2O molecules and double chains. Left- and right-handed 21 helices formed by the Hasba(-) anions are arranged alternately within the two-dimensional supramolecular double layers. Complex (2) exhibits a polymeric chain which is further extended into a three-dimensional supramolecular network through interchain hydrogen bonds. Complex (1) shows a reversible dehydration-rehydration behaviour, while complex (2) shows an irreversible dehydration-rehydration behaviour. PMID- 26146396 TI - Synthesis, characterization and crystal structures of the bidentate Schiff base N,N'-bis(2-nitrocinnamaldehyde)ethylenediamine and its complex with CuNCS and triphenylphosphane. AB - Reaction of copper(I) thiocyanate and triphenylphosphane with the bidentate Schiff base N,N'-bis(trans-2-nitrocinnamaldehyde)ethylenediamine {Nca2en, (1); systematic name (1E,1'E,2E,2'E)-N,N'-(ethane-1,2-diyl)bis[3-(2-nitrophenyl)prop-2 en-1-imine]}, C20H18N4O4, in a 1:1:1 molar ratio in acetonitrile resulted in the formation of the complex {(1E,1'E,2E,2'E)-N,N'-(ethane-1,2-diyl)bis[3-(2 nitrophenyl)prop-2-en-1-imine]-kappa(2)N,N'}(thiocyanato kappaN)(triphenylphosphane-kappaP)copper(I)], [Cu(NCS)(C20H18N4O4)(C18H15P)] or [Cu(NCS)(Nca2en)(PPh3)], (2). The Schiff base and copper(I) complex have been characterized by elemental analyses, IR, electronic and (1)H NMR spectroscopy, and X-ray crystallography [from synchrotron data for (1)]. The molecule of (1) lies on a crystallographic inversion centre, with a trans conformation for the ethylenediamine unit, and displays significant twists from coplanarity of its nitro group, aromatic ring, conjugated chain and especially ethylenediamine segments. It acts as a bidentate ligand coordinating via the imine N atoms to the Cu(I) atom in complex (2), in which the ethylenediamine unit necessarily adopts a somewhat flattened gauche conformation, resulting in a rather bowed shape overall for the ligand. The NCS(-) ligand is coordinated through its N atom. The geometry around the Cu(I) atom is distorted tetrahedral, with a small N-Cu-N bite angle of 81.56 (12) degrees and an enlarged opposite angle of 117.29 (9) degrees for SCN Cu-P. Comparisons are made with the analogous Schiff base having no nitro substituents and with metal complexes of both ligands. PMID- 26146397 TI - New hydrophobic L-amino acid salts: maleates of L-leucine, L-isoleucine and L norvaline. AB - Crystals of maleates of three amino acids with hydrophobic side chains [L leucenium hydrogen maleate, C6H14NO2(+).C4H3O4(-), (I), L-isoleucenium hydrogen maleate hemihydrate, C6H14NO2(+).C4H3O4(-).0.5H2O, (II), and L-norvalinium hydrogen maleate-L-norvaline (1/1), C5H11NO2(+).C4H3O4(-).C5H12NO2, (III)], were obtained. The new structures contain C2(2)(12) chains, or variants thereof, that are a common feature in the crystal structures of amino acid maleates. The L leucenium salt is remarkable due to a large number of symmetrically non equivalent units (Z' = 3). The L-isoleucenium salt is a hydrate despite the fact that L-isoleucine is a nonpolar hydrophobic amino acid (previously known amino acid maleates formed hydrates only with lysine and histidine, which are polar and hydrophilic). The L-norvalinium salt provides the first example where the dimeric cation L-Nva...L-NvaH(+) was observed. All three compounds have layered noncentrosymmetric structures. Preliminary tests have shown the presence of the second harmonic generation (SGH) effect for all three compounds. PMID- 26146398 TI - Dicyclohexylammonium bromoacetate: a low molecular mass organogelator with a one dimensional secondary ammonium monocarboxylate (SAM) synthon. AB - The asymmetric unit of the title salt, C12H24N(+).C2H2BrO2(-), contains a dicyclohexylammonium cation connected to a bromoacetate anion by means of an N H...O hydrogen bond. In the crystal, the ion pairs assemble via N-H...O interactions, forming zigzag infinite chains parallel to the c axis with the (...H-N-H...O-C-O...)n motif that is considered to be a prerequisite for ensuring gelation properties of secondary ammonium monocarboxylate salts. The title salt was characterized by FT-IR, X-ray powder diffraction (XRPD), TG-DTA and (1)H NMR spectroscopy in solution. Gelation experiments revealed that dicyclohexylammonium bromoacetate forms molecular gels with dimethylformamide and dimethyl sulfoxide. Scanning electron microscopy (SEM) was used to reveal morphological features of dried gels. PMID- 26146399 TI - Accidental formation of Gd4(SiO4)2OTe: crystal structure and spectroscopic properties. AB - Designing new functional materials with increasingly complex compositions is of current interest in science and technology. Complex rare-earth-based chalcogenides have specific thermal, electrical, magnetic and optical properties. Tetragadolinium bis[tetraoxidosilicate(IV)] oxide telluride, Gd4(SiO4)2OTe, was obtained accidentally while studying the Gd2Te3-Cu2Te system. The crystal structure was determined by means of single-crystal X-ray diffraction. The compound crystallizes in the space group Pnma. Three symmetry-independent gadolinium sites were determined. The excitation and emission spectra were collected at room temperature and at 10 K. Gd4(SiO4)2OTe appears to be a promising optical material when doped with rare-earth ions. PMID- 26146400 TI - Four cocrystals of thymine with phenolic coformers: influence of the coformer on hydrogen bonding. AB - Cocrystals are molecular solids composed of at least two types of neutral chemical species held together by noncovalent forces. Crystallization of thymine [systematic name: 5-methylpyrimidine-2,4(1H,3H)-dione] with four phenolic coformers resulted in cocrystal formation, viz. catechol (benzene-1,2-diol) giving thymine-catechol (1/1), C5H6N2O2.C6H6O2, (I), resorcinol (benzene-1,3 diol) giving thymine-resorcinol (2/1), 2C5H6N2O2.C6H6O2, (II), hydroquinone (benzene-1,4-diol) giving thymine-hydroquinone (2/1), 2C5H6N2O2.C6H6O2, (III), and pyrogallol (benzene-1,2,3-triol) giving thymine-pyrogallol (1/2), C5H6N2O2.2C6H6O3, (IV). The resorcinol molecule in (II) occupies a twofold axis, while the hydroquinone molecule in (III) is situated on a centre of inversion. Thymine-thymine base pairing is common across all four structures, albeit with different patterns. In (I)-(III), the base pair is propagated into an infinite one-dimensional ribbon, whereas it exists as a discrete dimeric unit in (IV). In (I)-(III), the two donor N atoms and one carbonyl acceptor O atom of thymine are involved in thymine-thymine base pairing and the remaining carbonyl O atom is hydrogen bonded to the coformer. In contrast, in (IV), just one donor N atom and one acceptor O atom are involved in base pairing, and the remaining donor N atom and acceptor O atom of thymine form hydrogen bonds to the coformer molecules. Thus, the utilization of the donor and acceptor atoms of thymine in the hydrogen bonding is influenced by the coformers. PMID- 26146401 TI - A chalcone showing positional disorder, two related diarylcyclohexenones showing enantiomeric disorder and a related hydroxyterphenyl, all derived from simple carbonyl precursors. AB - Four compounds are reported, all of which lie along a versatile reaction pathway which leads from simple carbonyl compounds to terphenyls. (2E)-1-(2,4 Dichlorophenyl)-3- [4-(prop-1-en-2-yl)phenyl]prop-2-en-1-one, C18H14Cl2O, (I), prepared from 4-(prop-1-en-2-yl)benzaldehyde and 2,4-dichloroacetophenone, exhibits disorder over two sets of atomic sites having occupancies of 0.664 (6) and 0.336 (6). The related chalcone (2E)-3-(4-chlorophenyl)-1-(4 fluorophenyl)prop-2-en-1-one reacts with acetone to produce (5RS)-3-(4 chlorophenyl)-5-[4-(propan-2-yl)phenyl]cyclohex-2-en-1-one, C21H21ClO, (II), which exhibits enantiomeric disorder with occupancies at the reference site of 0.662 (4) and 0.338 (4) for the (5R) and (5S) forms; the same chalcone reacts with methyl 3-oxobutanoate to give methyl (1RS,6SR)-4-(4-chlorophenyl)-6-[4 (propan-2-yl)phenyl]-2-oxocyclohex-3-ene-1-carboxylate, C23H23ClO3, (III), where the reference site contains both (1R,6S) and (1S,6R) forms with occupancies of 0.923 (3) and 0.077 (3), respectively. Oxidation, using 2,3-dichloro-5,6-dicyano 1,4-benzoquinone, of ethyl (1RS,6SR)-6-(4-bromophenyl)-4-(4-fluorophenyl)-2 oxocyclohex-3-ene-1-carboxylate, prepared in a similar manner to (II) and (III), produces ethyl 4''-bromo-4-fluoro-5'-hydroxy-1,1':3',1''-terphenyl-4' carboxylate, C21H16BrFO3, (IV), which crystallizes with Z' = 2 in the space group P-1. There are no significant intermolecular interactions in the structures of compounds (I) and (II), but for the major disorder component of compound (III), the molecules are linked into sheets by a combination of C-H...O and C H...pi(arene) hydrogen bonds. The two independent molecules of compound (IV) form two different centrosymmetric dimers, one built from inversion-related pairs of C H...O hydrogen bonds and the other from inversion-related pairs of C H...pi(arene) hydrogen bonds. Comparisons are made with related compounds. PMID- 26146402 TI - Hydrothermal synthesis, crystal structure and photoluminescence of two homochiral zinc(II) coordination polymers. AB - Metal-organic frameworks (MOFs) have potentially useful applications and an intriguing variety of architectures and topologies. Two homochiral coordination polymers have been synthesized by the hydrothermal method, namely poly[(MU-N benzyl-L-phenylalaninato-kappa(4)O,O':O,N)(MU-formato-kappa(2)O:O')zinc(II)], [Zn(C16H16NO2)(HCOO)]n, (1), and poly[(MU-N-benzyl-L-leucinato kappa(4)O,O':O,N)(MU-formato-kappa(2)O:O')zinc(II)], [Zn(C13H18NO2)(HCOO)]n, (2), and studied by single-crystal X-ray diffraction, elemental analyses, IR spectroscopy and fluorescence spectroscopy. Compounds (1) and (2) each have a two dimensional layer structure, with the benzyl or isobutyl groups of the ligands directed towards the interlayer interface. Photoluminescence investigations show that both (1) and (2) display a strong emission in the blue region. PMID- 26146403 TI - Structure determination of KScS2, RbScS2 and KLnS2 (Ln = Nd, Sm, Tb, Dy, Ho, Er, Tm and Yb) and crystal-chemical discussion. AB - The title structures of KScS2 (potassium scandium sulfide), RbScS2 (rubidium scandium sulfide) and KLnS2 [Ln = Nd (potassium neodymium sufide), Sm (potassium samarium sulfide), Tb (potassium terbium sulfide), Dy (potassium dysprosium sulfide), Ho (potassium holmium sulfide), Er (potassium erbium sulfide), Tm (potassium thulium sulfide) and Yb (potassium ytterbium sulfide)] are either newly determined (KScS2, RbScS2 and KTbS2) or redetermined. All of them belong to the alpha-NaFeO2 structure type in agreement with the ratio of the ionic radii r(3+)/r(+). KScS2, the member of this structural family with the smallest trivalent cation, is an extreme representative of these structures with rare earth trivalent cations. The title structures are compared with isostructural alkali rare earth sulfides in plots showing the dependence of several relevant parameters on the trivalent cation crystal radius; the parameters thus compared are c, a and c/a, the thicknesses of the S-S layers which contain the respective constituent cations, the sulfur fractional coordinates z(S(2-)) and the bond valence sums. PMID- 26146404 TI - Synthesis and characterization of (6-{[2-(pyridin-2 yl)hydrazinylidene]methyl}pyridin-2-yl)methanol: a supramolecular and topological study. AB - Hydrazones exhibit a versatile chemistry and are of interest for their potential use as functional molecular systems capable of undergoing reversible changes of configuration, i.e. E/Z isomerization. The title compound, C12H12N4O, has an E configuration with respect to the hydrazone C=N bond. The crystal packing is formed by N-H...N and O-H...N hydrogen bonds that give a two-dimensional layer structure and C-H...C interactions associated with layer stacking to produce the three-dimensional supramolecular structure. These intermolecular interactions were analyzed and quantified by the Hirshfeld surface method and the two dimensional supramolecular arrangement was topologically simplified as a hcb network. PMID- 26146405 TI - Synthesis, structure and luminescence properties of two new acylamide metal organic frameworks showing 4-connected CdSO4 and a threefold interpenetrating dia net. AB - Two new acylamide metal-organic frameworks (MOFs), based on mixed N- and O-donor ligands, with 4-connected topologies have been obtained, namely poly[[MU2 N(1),N(4)-bis(pyridin-3-yl)terephthalamide]bis(MU3-4,4' oxydibenzoato)dizinc(II)], [Zn2(C14H8O5)2(C18H14N4O2)]n, (1), and poly[[(MU2 benzene-1,4-dicarboxylato)[MU2-N(4),N(4')-bis(pyridin-3-yl)-[1,1'-biphenyl]-4,4' dicarboxamide]dicadmium(II)] dihydrate], {[Cd(C8H4O4)(C24H18N4O2)].2H2O}n, (2). Complex (1) is a 4-connected CdSO4 net with no interpenetration, where the Zn(II) cation is regarded as a 4-connecting node with square geometry. Complex (2) is a 4-connected dia net with threefold interpenetration, where the Cd(II) cation acts as a 4-connecting node with tetrahedral geometry. The results of thermogravimetric and luminescence analyses are described in detail. PMID- 26146407 TI - Automatic structure recovery for additive models. AB - We propose an automatic structure recovery method for additive models, based on a backfitting algorithm coupled with local polynomial smoothing, in conjunction with a new kernel-based variable selection strategy. Our method produces estimates of the set of noise predictors, the sets of predictors that contribute polynomially at different degrees up to a specified degree M, and the set of predictors that contribute beyond polynomially of degree M. We prove consistency of the proposed method, and describe an extension to partially linear models. Finite-sample performance of the method is illustrated via Monte Carlo studies and a real-data example. PMID- 26146408 TI - Eggshell porosity covaries with egg size among female House Wrens (Troglodytes aedon) but is unrelated to incubation onset and egg-laying order within clutches. AB - In birds, the duration of egg incubation (the time from incubation onset to hatching) can affect multiple components of nest success, but what affects incubation duration? Previous studies suggest that incubation duration is affected by both parental behavior and components of the egg, which have yet to be determined. One egg component that may be related to incubation behavior and the time until hatching is eggshell porosity, which affects the exchange of metabolic gasses and water vapor across the shell and, thus, the speed of embryonic development and incubation duration. We tested whether eggshell porosity was associated with the timing of incubation onset by female House Wrens (Troglodytes aedon Vieillot, 1809), and whether porosity varied within clutches in a manner that might be associated with incubation periods and hatching patterns (i.e., synchronous vs. asynchronous hatching). Eggshell porosity was unrelated to the onset of maternal incubation and did not differ between early and later-laid eggs within clutches, but differed significantly among females and covaried with egg size. We conclude that producing all eggshells of similar porosity within clutches, while adjusting incubation onset once most or all eggs are laid, provide facultative maternal control over variation in hatching patterns. PMID- 26146406 TI - N-Myc and STAT Interactor regulates autophagy and chemosensitivity in breast cancer cells. AB - We have previously reported that expression of NMI (N-myc and STAT interactor) is compromised in invasive breast cancers. We also demonstrated that loss of NMI expression promotes epithelial-mesenchymal-transition and results in enhanced invasive ability of breast cancer cells. Additionally we had demonstrated that restoration of NMI expression reduced breast cancer xenograft growth and downregulated Wnt and TGFbeta/SMAD signaling. Here we present our observations that NMI expression drives autophagy. Our studies were promoted by our observation that NMI expressing breast cancer cells showed autophagic vacuoles and LC3 processing. Additionally, we found that NMI expression increased the cisplatin sensitivity of the breast cancer cells. Our mechanistic investigations show that NMI prompts activation of GSK3-beta. This multifunctional kinase is an upstream effector of the TSC1/TSC2 complex that regulates mTOR signaling. Inhibition of GSK3-beta activity in NMI expressing cells activated mTOR signaling and decreased the cells' autophagic response. Additionally we demonstrate that a key component of autophagy, DNA-damage regulated autophagy modulator 1 (DRAM1), is regulated by NMI. Our TCGA database analysis reveals concurrent expression of NMI and DRAM1 in breast cancer specimens. We present evidence that NMI sensitizes breast cancer cells to cisplatin treatment through DRAM1 dependent autophagy. PMID- 26146409 TI - Developing a smartphone software package for predicting atmospheric pollutant concentrations at mobile locations. AB - There is considerable evidence that exposure to air pollution is harmful to health. In the U.S., ambient air quality is monitored by Federal and State agencies for regulatory purposes. There are limited options, however, for people to access this data in real-time which hinders an individual's ability to manage their own risks. This paper describes a new software package that models environmental concentrations of fine particulate matter (PM2.5), coarse particulate matter (PM10), and ozone concentrations for the state of Oregon and calculates personal health risks at the smartphone's current location. Predicted air pollution risk levels can be displayed on mobile devices as interactive maps and graphs color-coded to coincide with EPA air quality index (AQI) categories. Users have the option of setting air quality warning levels via color-coded bars and were notified whenever warning levels were exceeded by predicted levels within 10 km. We validated the software using data from participants as well as from simulations which showed that the application was capable of identifying spatial and temporal air quality trends. This unique application provides a potential low-cost technology for reducing personal exposure to air pollution which can improve quality of life particularly for people with health conditions, such as asthma, that make them more susceptible to these hazards. PMID- 26146410 TI - Developmental trajectories of writing skills in first grade: Examining the effects of SES and language and/or speech impairments. AB - We examined growth trajectories of writing and the relation of children's socio economic status, and language and/or speech impairment to the growth trajectories. First grade children (N = 304) were assessed on their written composition in the fall, winter, and spring, and their vocabulary and literacy skills in the fall. Children's SES had a negative effect on writing quality and productivity. Children with language and/or speech impairment had lower scores than typically developing children in the quality and productivity of writing. Even after accounting for their vocabulary and literacy skills, students with language and/or speech impairment had lower scores in the quality and organization of writing. Growth rates in writing were not different as a function of children's SES and language/speech impairment status. Theoretical and practical implications are discussed. PMID- 26146411 TI - Religious Affiliation, Ethnicity, and Child Mortality in Chiapas, Mexico. AB - We investigate whether there is a relationship between religious affiliation and child mortality among indigenous and nonindigenous groups in Chiapas, Mexico. Our analysis relies on Brass-type estimates of child mortality by ethnicity and religious affiliation and multivariate analyses that adjust for various socioeconomic and demographic factors. The data are from the 2000 Mexican Census 10 percent sample. Among indigenous people, Presbyterians have lower rates of child mortality than Catholics. However, no significant differentials are found in child mortality by religious affiliation among nonindigenous people. The indigenous health ministry of the Presbyterian Church and the social and cultural transformations that tend to accompany religious conversion may have an impact on child survival among disadvantaged populations such as the indigenous people in Chiapas. PMID- 26146412 TI - Brachypodium distachyon exhibits compatible interactions with Oculimacula spp. and Ramularia collo-cygni, providing the first pathosystem model to study eyespot and ramularia leaf spot diseases. AB - Brachypodium distachyon (Bd) has established itself as an essential tool for comparative genomic studies in cereals and increasing attention is being paid to its potential as a model pathosystem. Eyespot and ramularia leaf spot (RLS) are important diseases of wheat, barley and other small-grain cereals for which very little is known about the mechanisms of host resistance despite urgent requirements for plant breeders to develop resistant varieties. This work aimed to test the compatibility of interaction of two Bd accessions with the cereal pathogens Oculimacula spp. and Ramularia collo-cygni, the causal agents of eyespot and RLS diseases, respectively. Results showed that both Bd accessions developed symptoms similar to those on the natural host for all pathogen species tested. Microscopy images demonstrated that R. collo-cygni produced secondary conidia and both Oculimacula spp. formed characteristic infection structures on successive tissue layers. Visual disease assessment revealed that quantitative differences in disease severity exist between the two Bd accessions. The results presented here provide the first evidence that Bd is compatible with the main causal agents of eyespot and RLS diseases, and suggest that future functional genetic studies can be undertaken to investigate the mechanisms of eyespot and RLS disease resistance using Bd. PMID- 26146413 TI - LAMP assay and rapid sample preparation method for on-site detection of flavescence doree phytoplasma in grapevine. AB - In Europe the most devastating phytoplasma associated with grapevine yellows (GY) diseases is a quarantine pest, flavescence doree (FDp), from the 16SrV taxonomic group. The on-site detection of FDp with an affordable device would contribute to faster and more efficient decisions on the control measures for FDp. Therefore, a real-time isothermal LAMP assay for detection of FDp was validated according to the EPPO standards and MIQE guidelines. The LAMP assay was shown to be specific and extremely sensitive, because it detected FDp in all leaf samples that were determined to be FDp infected using quantitative real-time PCR. The whole procedure of sample preparation and testing was designed and optimized for on site detection and can be completed in one hour. The homogenization procedure of the grapevine samples (leaf vein, flower or berry) was optimized to allow direct testing of crude homogenates with the LAMP assay, without the need for DNA extraction, and was shown to be extremely sensitive. PMID- 26146414 TI - Emigration from China in Comparative Perspective. AB - Comparative research on international migration has increasingly focused on immigrant integration rather than the process of emigration. By investigating the different streams of Chinese migration to the United States and Europe, as well as the different stages of Chinese migration to the U.S., this study examines the way in which both receiving and sending contexts combine to shape the process of emigration. Using data from a 2002-2003 survey of emigration from China's Fujian Province, we demonstrate that under restrictive exit and entry policies and high barriers to migration (i.e., clandestine migration from Fuzhou to the U.S.), resources such as migrant social capital, political capital (cadre resources), and human capital all play a crucial role in the emigration process. However, the roles of these resources in the migration process are limited when migration barriers are sufficiently low and when local governments adopt proactive policies promoting emigration (i.e., legal migration from Mingxi to Europe). Comparisons over time suggest that the importance of migrant social capital, political capital, and human capital has strongly persisted for Fuzhou-US emigration, as a result of tightening exit and entry policies. Despite these marked differences between Fuzhou and Mingxi emigration, the results also point to two general processes that are highly consistent across settings and over time-the cumulative causation of migration and the advantage conferred by traditional positional power (cadre status). PMID- 26146415 TI - The Growth of Protestantism in Brazil and Its Impact on Male Earnings, 1970-2000. AB - Protestantism has expanded rapidly in Brazil in recent decades. The question we tackle in this paper is whether Protestantism has had a positive influence on male earnings in this setting, either through its influence on health and productivity, by way of social networks or employer favor and reduced discrimination, or through other mechanisms. We tackle the problem of the selectivity of religious conversion and affiliation using microdata from the Brazilian censuses of 1970, 1980, 1991, and 2000, and analyzing the association between Protestantism and earnings at the group rather than the individual level. Our results show a strong association between the proportion of Protestants in a region, and the earnings of men in one educational group: those with less than five years of education. Upon introducing race into our models, we found that the association between religion and the earnings of less educated men is concentrated in regions in which there is a substantial non-white population. The relationships we have uncovered contribute to the literature on racial inequality and discrimination in Brazil, which to date has given little space to the role of religion in moderating the pernicious effect of race on economic outcomes in Brazil. The substantial association we found between religion and earnings contrasts with much of the research that has been carried out on the influence of religion on earnings in the United States. PMID- 26146417 TI - Hemodilution for acute ischemic stroke. PMID- 26146416 TI - Extension of the Optimized Virtual Fields Method to estimate viscoelastic material parameters from 3D dynamic displacement fields. AB - In-vivo measurement of the mechanical properties of soft tissues is essential to provide necessary data in biomechanics and medicine (early cancer diagnosis, study of traumatic brain injuries, etc.). Imaging techniques such as Magnetic Resonance Elastography (MRE) can provide 3D displacement maps in the bulk and in vivo, from which, using inverse methods, it is then possible to identify some mechanical parameters of the tissues (stiffness, damping etc.). The main difficulties in these inverse identification procedures consist in dealing with the pressure waves contained in the data and with the experimental noise perturbing the spatial derivatives required during the processing. The Optimized Virtual Fields Method (OVFM) [1], designed to be robust to noise, present natural and rigorous solution to deal with these problems. The OVFM has been adapted to identify material parameter maps from Magnetic Resonance Elastography (MRE) data consisting of 3-dimensional displacement fields in harmonically loaded soft materials. In this work, the method has been developed to identify elastic and viscoelastic models. The OVFM sensitivity to spatial resolution and to noise has been studied by analyzing 3D analytically simulated displacement data. This study evaluates and describes the OVFM identification performances: different biases on the identified parameters are induced by the spatial resolution and experimental noise. The well-known identification problems in the case of quasi-incompressible materials also find a natural solution in the OVFM. Moreover, an a posteriori criterion to estimate the local identification quality is proposed. The identification results obtained on actual experiments are briefly presented. PMID- 26146418 TI - An efficient and mild oxidant for the synthesis of s-tetrazines. AB - PhI(OAc)2 serves as a mild and effective oxidant for the synthesis of s-tetrazine derivatives- molecules of emerging significance to the field of bioorthogonal chemistry. This reagent serves as a complementary oxidant to harsher nitrous reagents. Use of PhI(OAc)2 improves the synthesis of 5-amino-di(pyridin-2-yl)-s tetrazine, a molecule that has been broadly used for cellular imaging and nuclear medicine. The generality of PhI(OAc)2 as the oxidant for tetrazine synthesis is demonstrated for nine tetrazines in 75-98% yield. PMID- 26146419 TI - Inhibition and breaking of advanced glycation end-products (AGEs) with bis-2 aminoimidazole derivatives. AB - Advanced glycation end-products (AGEs), unregulated modifications to host macromolecules that occur as a result of metabolic dysregulation, play a role in many diabetes related complications, inflammation and aging, and may lead to increased cardiovascular risk. Small molecules that have the ability to inhibit AGE formation, and even break preformed AGEs have enormous therapeutic potential in the treatment of these disease states. We report the screening of a series of 2-aminoimidazloles for anti-AGE activity, and the identification of a bis-2 aminoimidazole lead compound that possesses superior AGE inhibition and breaking activity compared to the known AGE inhibitor aminoguanidine. PMID- 26146420 TI - Biosynthesis of the C15-acetogenin laurepoxide may involve bromine-induced skeletal rearrangement of a Delta4-oxocene precursor. AB - An electrophilic bromine catalyzed skeletal rearrangement of an Delta4-oxocene to an epoxy furan has been described. This skeletal rearrangement suggests a plausible mechanism for the biosynthesis of the C15-acetogenin laurepoxide. PMID- 26146421 TI - Evaluation of a high-EPA oil from transgenic Camelina sativa in feeds for Atlantic salmon (Salmo salar L.): Effects on tissue fatty acid composition, histology and gene expression. AB - Currently, one alternative for dietary fish oil (FO) in aquafeeds is vegetable oils (VO) that are devoid of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs). Entirely new sources of n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids through de novo production are a potential solution to fill the gap between supply and demand of these important nutrients. Camelina sativa was metabolically engineered to produce a seed oil (ECO) with > 20% EPA and its potential to substitute for FO in Atlantic salmon feeds was tested. Fish were fed with one of the three experimental diets containing FO, wild-type camelina oil (WCO) or ECO as the sole lipid sources for 7 weeks. Inclusion of ECO did not affect any of the performance parameters studied and enhanced apparent digestibility of individual n-6 and n-3 PUFA compared to dietary WCO. High levels of EPA were maintained in brain, liver and intestine (pyloric caeca), and levels of DPA and DHA were increased in liver and intestine of fish fed ECO compared to fish fed WCO likely due to increased LC-PUFA biosynthesis based on up-regulation of the genes. Fish fed ECO showed slight lipid accumulation within hepatocytes similar to that with WCO, although not significantly different to fish fed FO. The regulation of a small number of genes could be attributed to the specific effect of ECO (311 features) with metabolism being the most affected category. The EPA oil from transgenic Camelina (ECO) could be used as a substitute for FO, however it is a hybrid oil containing both FO (EPA) and VO (18:2n-6) fatty acid signatures that resulted in similarly mixed metabolic and physiological responses. PMID- 26146422 TI - Optimizing dietary levels of menhaden and soybean oils and soybean lecithin for pre-gonadal somatic growth in juveniles of the sea urchin Lytechinus variegatus. AB - Dietary lipids serve as important sources of energy and essential fatty acids for aquatic animals. Sources of animal and plant oils are increasingly limited as well as expensive, and dietary requirements associated with the inclusion of these oils must be carefully evaluated to facilitate sustainable and affordable formulations. In this study, we investigated quantities of menhaden oil (MO) with and without soybean lecithin or soybean oil (SO) to determine appropriate levels for optimal somatic growth for pre-gonadal juvenile Lytechinus variegatus. We prepared semi-purified diets that varied in neutral lipid content (0, 2, 4, or 8% dry matter) and soy lecithin (0 or 2%) and exchanged lipids reciprocally with purified starch while holding constant all other nutrients. We maintained laboratory-reared juvenile L. variegatus (average initial wet weight 82 +/- 0.7 mg, mean +/- SE , n = 9 treatment-1) in recirculating seawater systems and fed each daily a sub-satiation ration for five weeks. We assessed wet weights and test diameters every two weeks and at the end of the experiment (5 wk). Level of MO with or without soybean lecithin did not significantly affect wet weight gain; however, increasing levels of SO in the diet reduced wet weight gain and dry matter production efficiency and increased feed conversion ratio. Dry gut weight was positively correlated with level of MO. Lipid level in the gut increased with increasing dietary lipid level, regardless of source. These data suggest the composition of the SO is inhibitory for either nutrient absorption or metabolic processes associated with growth at this life stage. Diets containing total lipid levels of approximately 5 to 6% that include sources of n-3 fatty acids may support optimal growth for pre-gonadal juvenile L. variegatus. PMID- 26146423 TI - LEARNING NONADJACENT DEPENDENCIES IN PHONOLOGY: TRANSPARENT VOWELS IN VOWEL HARMONY. AB - Nonadjacent dependencies are an important part of the structure of language. While the majority of syntactic and phonological processes occur at a local domain, there are several processes that appear to apply at a distance, posing a challenge for theories of linguistic structure. This article addresses one of the most common nonadjacent phenomena in phonology: transparent vowels in vowel harmony. Vowel harmony occurs when adjacent vowels are required to share the same phonological feature value (e.g. V+F C V+F). However, transparent vowels create a second-order nonadjacent pattern because agreement between two vowels can 'skip' the transparent neutral vowel in addition to consonants (e.g. V+F C VT-F C V+F). Adults are shown to display initial learning biases against second-order nonadjacency in experiments that use an artificial grammar learning paradigm. Experiments 1-3 show that adult learners fail to learn the second-order long distance dependency created by the transparent vowel (as compared to a control condition). In experiments 4-5, training in terms of overall exposure as well as the frequency of relevant transparent items was increased. With adequate exposure, learners reliably generalize to novel words containing transparent vowels. The experiments suggest that learners are sensitive to the structure of phonological representations, even when learning occurs at a relatively rapid pace. PMID- 26146424 TI - 64.1: Display Technologies for Therapeutic Applications of Virtual Reality. AB - A paradigm shift in image source technology for VR helmets is needed. Using scanning fiber displays to replace LCD displays creates lightweight, safe, low cost, wide field of view, portable VR goggles ideal for reducing pain during severe burn wound care in hospitals and possibly in austere combat-transport environments. PMID- 26146425 TI - Semiparametric Relative-risk Regression for Infectious Disease Transmission Data. AB - This paper introduces semiparametric relative-risk regression models for infectious disease data. The units of analysis in these models are pairs of individuals at risk of transmission. The hazard of infectious contact from i to j consists of a baseline hazard multiplied by a relative risk function that can be a function of infectiousness covariates for i, susceptibliity covariates for j, and pairwise covariates. When who-infects-whom is observed, we derive a profile likelihood maximized over all possible baseline hazard functions that is similar to the Cox partial likelihood. When who-infects-whom is not observed, we derive an EM algorithm to maximize the profile likelihood integrated over all possible combinations of who-infected-whom. This extends the most important class of regression models in survival analysis to infectious disease epidemiology. These methods can be implemented in standard statistical software, and they will be able to address important scientific questions about emerging infectious diseases with greater clarity, flexibility, and rigor than current statistical methods allow. PMID- 26146426 TI - A Review of Ionospheric Scintillation Models. AB - This is a general review of the existing climatological models of ionospheric radio scintillation for high and equatorial latitudes. Trans-ionospheric communication of radio waves from transmitter to user is affected by the ionosphere which is highly variable and dynamic in both time and space. Scintillation is the term given to irregular amplitude and phase fluctuations of the received signals and related to the electron density irregularities in the ionosphere. Key sources of ionospheric irregularities are plasma instabilities; every irregularities model is based on the theory of radio wave propagation in random media. It is important to understand scintillation phenomena and the approach of different theories. Therefore, we have briefly discussed the theories that are used to interpret ionospheric scintillation data. The global morphology of ionospheric scintillation is also discussed briefly. The most important (in our opinion) analytical and physical models of scintillation are reviewed here. PMID- 26146427 TI - [Demographic Dynamics and Educational Inequality in Mexico]. AB - This paper seeks to explore the link between educational processes and Mexico's demographic dynamic. In the tradition of thought on population and development, it has been hypothesized that the population growth rate, family size and migration influence the accumulation of human capital among the school-age population. This study explores the link between the academic performance of youth between the age of 14 and 23 and the youth dependency ratio, teenage fertility and internal and international migration, using data aggregated at the municipal level for the year 2000. The analysis uses indicators on the educational supply at the municipal level based on the administrative statistics of the Public Education Secretariat (SEP). PMID- 26146428 TI - Relationships between Cloninger's, Zuckerman's, and Eysenck's dimensions of personality. PMID- 26146429 TI - Family Obligation Across Contexts: Hispanic Youth in North Carolina and Southern California. AB - Over the past decade, the Hispanic population has grown in areas with little to no history of recent immigration. Prior research comparing Hispanics in new and established destinations has chiefly focused on differences in socioeconomic indicators of assimilation. Our paper departs from this work by shifting the focus to sociocultural outcomes. Specifically, we use data from Los Angeles and North Carolina to examine differences in the strength of family obligation (N=552). We find that demographic characteristics explain all of the geographic difference in family obligation between these locations. However, we also find that co-ethnic concentration is positively correlated with adolescents' endorsement of future family support, once ethnic identity is included in the analysis. PMID- 26146430 TI - Long Term Influences of Age-Education Transition on the Brazilian Labour Market. AB - The objective of this study is to estimate the long term mean earnings of the male Brazilian population, taking into account the ageing process of the population and the increase in educational attainment. Using census data, household sample surveys, as well as population and education projections, estimates indicate that an ageing population and an increase in education will have a 2 percent impact on the annual growth of an average income in Brazil by 2050. The challenge for the future is to improve the proportion of the Brazilian population with completed college degrees. PMID- 26146431 TI - Effects of Conservation Policies on Forest Cover Change in Giant Panda Habitat Regions, China. AB - After long periods of deforestation, forest transition has occurred globally, but the causes of forest transition in different countries are highly variable. Conservation policies may play important roles in facilitating forest transition around the world, including China. To restore forests and protect the remaining natural forests, the Chinese government initiated two nationwide conservation policies in the late 1990s -- the Natural Forest Conservation Program (NFCP) and the Grain-To-Green Program (GTGP). While some studies have discussed the environmental and socioeconomic effects of each of these policies independently and others have attributed forest recovery to both policies without rigorous and quantitative analysis, it is necessary to rigorously quantify the outcomes of these two conservation policies simultaneously because the two policies have been implemented at the same time. To fill the knowledge gap, this study quantitatively evaluated the effects of the two conservation policies on forest cover change between 2001 and 2008 in 108 townships located in two important giant panda habitat regions -- the Qinling Mountains region in Shaanxi Province and the Sichuan Giant Panda Sanctuary in Sichuan Province. Forest cover change was evaluated using a land-cover product (MCD12Q1) derived from the Moderate Resolution Imaging Spectroradiometer (MODIS). This product proved to be highly accurate in the study region (overall accuracy was ca. 87%, using 425 ground truth points collected in the field), thus suitable for the forest change analysis performed. Results showed that within the timeframe evaluated, most townships in both regions exhibited either increases or no changes in forest cover. After accounting for a variety of socioeconomic and biophysical attributes, an Ordinary Least Square (OLS) regression model suggests that the two policies had statistically significant positive effects on forest cover change after seven years of implementation, while population density, percent agricultural population, road density, and initial forest cover (i.e. in 2001) had significant negative effects. The methods and results from this study will be useful for continuing the implementation of these conservation policies, for the development of future giant panda habitat conservation projects, and for achieving forest sustainability in China and elsewhere. PMID- 26146432 TI - Biological activity of alginate and its effect on pancreatic lipase inhibition as a potential treatment for obesity. AB - Alginates are classed as a dietary fibre and have been shown to inhibit digestive enzymes in vitro, and therefore could be used as an obesity treatment. The current study aims to assess whether alginate in a bread vehicle maintains its inhibition properties despite cooking and digestion, and may therefore be used as a potential treatment for obesity. After 180 min in a model gut that replicates digestion in the mouth, stomach and small intestines alginate bread (AB), control bread (CB), CB with Manucol(r) DM alginate, free DM alginate and model gut solution were collected. DM, LFR 5/60 and SF200 were heated at 37 degrees C and 200 degrees C, with DM also heated at 50, 100 and 150 degrees C. Samples from the model gut and heated alginate were assessed for molecular size and inhibition properties using viscosity, gel filtration and a lipase turbidity assay. AB does not significantly increase viscosity in the model gut. Viscosity of alginate reduces beyond 100 degrees C, although alginate retains its inhibition properties up to 150 degrees C. Cooking into the bread does not reduce the molecular size of the alginate or affect its inhibition properties. These data demonstrate the robustness of alginates lipase inhibition despite the cooking process and digestion. Therefore adding alginate to a bread vehicle may have the potential in the treatment for obesity. PMID- 26146433 TI - Pubertal Timing, Peer Victimization, and Body Esteem Differentially Predict Depressive Symptoms in African American and Caucasian Girls. AB - This study prospectively examined pubertal timing and peer victimization as interactive predictors of depressive symptoms in a racially diverse community sample of adolescents. We also expanded on past research by assessing body esteem as a mechanism by which pubertal timing and peer victimization confer risk for depression. In all, 218 adolescents (53.4% female, 49.3% African American, 50.7% Caucasian) completed both a baseline assessment and a follow-up assessment approximately 8 months later. Early maturing Caucasian girls and late maturing African American girls experienced the greatest increases in depressive symptoms at follow-up if they experienced higher levels of peer victimization between baseline and follow-up. Furthermore, body esteem significantly mediated the relationship between pubertal timing, peer victimization, and depressive symptoms for girls of both races. The interaction of pubertal timing and peer victimization did not predict depressive symptoms for boys of either race. These results support body esteem as a mechanism that contributes to increased depression among girls in adolescence-despite a differential impact of pubertal timing for Caucasian and African American girls. PMID- 26146434 TI - Resisting pressure from peers to engage in sexual behavior: What communication strategies do early adolescent Latino Girls use? AB - A content analysis of early adolescent (M=12.02 years) Latino girls' (n=44) responses to open-ended questions imbedded in an electronic survey was conducted to explore strategies girls may use to resist peer pressure with respect to sexual behavior. Analysis yielded 341 codable response units, 74% of which were consistent with the REAL typology (i.e., refuse, explain, avoid, and leave) previously identified in adolescent substance use research. However, strategies reflecting a lack of resistance (11%) and inconsistency with communication competence (e.g., aggression, involving authorities) were also noted (15%). Frequency of particular strategies varied according to offer type, suggesting a variety of strategies may be needed to resist the peer pressure that puts early adolescent girls at risk for engaging in sexual behavior. Findings argue for universality of the REAL typology, building communication competence skills for conflict resolution in dating situations, and including peer resistance strategies in adolescent pregnancy prevention programs. PMID- 26146435 TI - Reactivity of Gold Hydrides: O2 Insertion into the Au-H Bond. AB - Dioxygen reacts with the gold(I) hydride (IPr)AuH under insertion to give the hydroperoxide (IPr)AuOOH, a long-postulated reaction in gold catalysis and the first demonstration of O2 activation by Au-H in a well-defined system. Subsequent condensation gave the peroxide (IPr)Au-OO-Au(IPr) (IPr = 1,3-bis(2,6 diisopropylphenyl)imidazol-2-ylidene). The reaction kinetics are reported, as well as the reactivity of Au(I) hydrides with radical scavengers. PMID- 26146436 TI - Gold(I) and Gold(III) Complexes of Cyclic (Alkyl)(amino)carbenes. AB - The chemistry of Au(I) complexes with two types of cyclic (alkyl)(amino)carbene (CAAC) ligands has been explored, using the sterically less demanding dimethyl derivative Me2CAAC and the 2-adamantyl ligand AdCAAC. The conversion of (AdCAAC)AuCl into (AdCAAC)AuOH by treatment with KOH is significantly accelerated by the addition of tBuOH. (AdCAAC)AuOH is a convenient starting material for the high-yield syntheses of (AdCAAC)AuX complexes by acid/base and C-H activation reactions (X = OAryl, CF3CO2, N(Tf)2, C2Ph, C6F5, C6HF4, C6H2F3, CH2C(O)C6H4OMe, CH(Ph)C(O)Ph, CH2SO2Ph), while the cationic complexes [(AdCAAC)AuL]+ (L = CO, CN t Bu) and (AdCAAC)AuCN were obtained by chloride substitution from (AdCAAC)AuCl. The reactivity toward variously substituted fluoroarenes suggests that (AdCAAC)AuOH is able to react with C-H bonds with pKa values lower than about 31.5. This, together with the spectroscopic data, confirm the somewhat stronger electron-donor properties of CAAC ligands in comparison to imidazolylidene-type N heterocyclic carbenes (NHCs). In spite of this, the oxidation of Me2CAAC and AdCAAC gold compounds is much less facile. Oxidations proceed with C-Au cleavage by halogens unless light is strictly excluded. The oxidation of (AdCAAC)AuCl with PhICl2 in the dark gives near-quantitative yields of (AdCAAC)AuCl3, while [Au(Me2CAAC)2]Cl leads to trans-[AuCl2(Me2CAAC)2]Cl. In contrast to the chemistry of imidazolylidene-type gold NHC complexes, oxidation products containing Au-Br or Au-I bonds could not be obtained; whereas the reaction with CsBr3 cleaves the Au-C bond to give mixtures of [AdCAAC-Br]+[AuBr2]- and [(AdCAAC-Br)]+ [AuBr4]-, the oxidation of (AdCAAC)AuI with I2 leads to the adduct (AdCAAC)AuI.I2. Irrespective of the steric demands of the CAAC ligands, their gold complexes proved more resistant to oxidation and more prone to halogen cleavage of the Au-C bonds than gold(I) complexes of imidazole-based NHC ligands. PMID- 26146437 TI - Contrasting Anticancer Activity of Half-Sandwich Iridium(III) Complexes Bearing Functionally Diverse 2-Phenylpyridine Ligands. AB - We report the synthesis, characterization, and antiproliferative activity of 15 iridium(III) half-sandwich complexes of the type [(eta5-Cp*)Ir(2-(R'-phenyl)-R pyridine)Cl] bearing either an electron-donating (-OH, -CH2OH, -CH3) or electron withdrawing (-F, -CHO, -NO2) group at various positions on the 2-phenylpyridine (2-PhPy) chelating ligand giving rise to six sets of structural isomers. The X ray crystal structures of [(eta5-Cp*)Ir(2-(2'-fluorophenyl)pyridine)Cl] (1) and [(eta5-Cp*)Ir(2-(4'-fluorophenyl)pyridine)Cl] (2) exhibit the expected "piano stool" configuration. DFT calculations showed that substituents caused only localized effects on the electrostatic potential surface of the chelating 2-PhPy ligand of the complexes. Hydrolysis of all complexes is rapid, but readily reversed by addition of NaCl. The complexes show preferential binding to 9 ethylguanine over 9-methyladenine and are active catalysts for the oxidation of NADH to NAD+. Antiproliferative activity experiments in A2780 ovarian, MCF-7 breast, A549 lung, and HCT116 colon cancer cell lines showed IC50 values ranging from 1 to 89 MUM, with the most potent complex, [(eta5-Cp*)Ir(2-(2' methylphenyl)pyridine)Cl] (13) (A2780 IC50 = 1.18 MUM), being 10* more active than the parent, [(eta5-Cp*)Ir(2-phenylpyridine)Cl], and 2* more active than [(eta5-CpxPh)Ir(2-phenylpyridine)Cl]. Intriguingly, contrasting biological activities are observed between structural isomers despite exhibiting similar chemical reactivity. For pairs of structural isomers both the nature and position of the functional group can affect the hydrophobicity of the complex. An increase in hydrophobicity resulted in enhanced cellular-iridium accumulation in A2780 ovarian cells, which generally gave rise to an increase in potency. The structural isomers [(eta5-Cp*)Ir(2-(4'-fluorophenyl)pyridine)Cl] (2) and [(eta5 Cp*)Ir(2-phenyl-5-fluoropyridine)Cl] (4) preferentially localized in the cytosol > membrane and particulate > nucleus > cytoskeleton. This work highlights the strong dependence of biological behavior on the nature and position of the substituent on the chelating ligand and shows how this class of organometallic anticancer complexes can be fine-tuned to increase their potency without using extended cyclopentadienyl systems. PMID- 26146438 TI - Promoting C-C Bond Coupling of Benzyne and Methyl Ligands in Electron-Deficient (triphos)Pt-CH3+ Complexes. AB - In situ generated benzyne reacts at room temperature with (triphos)Pt-CH3+ to form a five-coordinate pi-complex (2) that is isolable and stable in solution. Thermolysis of 2 at 60 degrees C generates (triphos)Pt(o-tolyl)+ (3), which is the product of formal migratory insertion of CH3- onto the coordinated benzyne. The reaction of 2 with the acid Ph2NH2+ yields toluene at room temperature over the course of 8 h, while the same reaction with 3 only proceeds to 40% conversion over 2 days. These data indicate that the protonolysis of 2 does not proceed by CH3 migration onto benzyne to form 3 followed by protodemetalation. Instead, the data suggest either that protonation of 2 is first and is followed by H migration to yield a PtIVPh(Me) dication or that this latter species is generated by direct protonolysis of coordinated benzyne prior to reductive elimination of toluene. PMID- 26146440 TI - The ratio of the spherical and flat Detectors at tissue surfaces during pleural photodynamic therapy. AB - An isotropic detector-based system was compared with a flat photodiode-based system in patients undergoing pleural photodynamic therapy. Isotropic and flat detectors were placed side by side in the chest cavity, for simultaneous in vivo dosimetry at surface locations for twelve patients. The treatment used 630nm laser to a total light irradiance of 30 J/cm2 (measured with the flat photodiodes) with photofrin(r) IV as the photosensitizer. Since the flat detectors were calibrated at 532nm, wavelength correction factors (WCF) were used to convert the calibration to 630nm (WCF between 0.542 and 0.703). The mean ratio between isotropic and flat detectors for all sites was linear to the accumulated fluence and was 3.4+/-0.6 or 2.1+/-0.4, with or without the wavelength correction for the flat detectors, respectively. The MUeff of the tissues was estimated to vary between 0.5 to 4.3 cm-1 for four sites (Apex, Posterior Sulcus, Anterior Chest Wall, and Posterior Mediastinum) assuming MUs' = 7 cm-1. Insufficient information was available to estimate MUeff directly for three other sites (Anterior Sulcus, Posterior Chest Wall, and Pericardium) primarily due to limited sample size, although one may assume the optical penetration in all sites to vary in the same range (0.5 to 4.3 cm-1). PMID- 26146441 TI - Light Dosimetry at Tissue Surfaces for Small Circular Fields. AB - Small circular light fields (<= 2 cm diameter) are sometimes used for photodynamic therapy of skin and recurrent breast cancers on the chest wall. These fields have lateral dimensions comparable to the effective mean free path of photons in the turbid medium, which causes reduced light fluence rate compared to that of a broad beam of uniform incident irradiance. We have compared Monte Carlo simulation with in-vivo dosimetry for circular fields (R = 0.25, 0.35, 0.5, 0.75, 1, 2, 3, and 8 cm) in a liquid phantom composed of intralipid and ink (us' = 4 - 20 cm-1 and ua = 0.1 cm-1) for wavelengths between 532 and 730 nm. We used anisotropy g = 0.9 and the index of refraction n = 1.4 for all Monte-Carlo simulations. The measured light fluence rate agrees with Monte-Carlo simulation to within 10%, with the measured value lower than that of the Monte-Carlo simulation on tissue surface. The ratio of the peak fluence rates between a circular beam and a broad beam under tissue is 0.58 - 0.96 or 0.84 - 1.00 for R between 0.5 - 2 cm and ueff = 1.1 or 2.0 cm-1, respectively. The ratio of peak fluence rate and incident irradiance for the broad beam is 5.9 and 6.4 for ueff = 1.1 and 2.0 cm-1, respectively. The optical penetration depth delta varies from 0.34 - 0.48 cm for R between 0.5 and 2 cm, with the corresponding delta = 0.51 cm for a broad beam. The ratio of fluence rate and incident irradiance above tissue surface is 1.4 - 1.8 or 1.9 - 2.2 for R between 0.5 - 2 cm and ueff = 1.1 or 2.0 cm-1, respectively. At depth of 0.2 cm inside tissue, Off-axis ratio OAR, defined as the ratio of fluence rate at off-axis distance r to that on the central axis, varies between 0.91 - 0.54 or 0.93 - 0.52 for off-axis distances r between 0.6 and 1.0 cm and ueff = 1.1 or 2.1 cm-1, respectively. In conclusion, in-vivo light dosimetry agrees with Monte-Carlo simulation for small field dosimetry provided the isotropic detector is corrected for the blind spot. The light fluence rates for small circular fields are substantially lower than that of the broad beam of the same incident irradiance. PMID- 26146442 TI - In vivo determination of the absorption and scattering spectra of the human prostate during photodynamic therapy. AB - A continuing challenge in photodynamic therapy is the accurate in vivo determination of the optical properties of the tissue being treated. We have developed a method for characterizing the absorption and scattering spectra of prostate tissue undergoing PDT treatment. Our current prostate treatment protocol involves interstitial illumination of the organ via cylindrical diffusing optical fibers (CDFs) inserted into the prostate through clear catheters. We employ one of these catheters to insert an isotropic white light point source into the prostate. An isotropic detection fiber connected to a spectrograph is inserted into a second catheter a known distance away. The detector is moved along the catheter by a computer-controlled step motor, acquiring diffuse light spectra at 2 mm intervals along its path. We model the fluence rate as a function of wavelength and distance along the detector's path using an infinite medium diffusion theory model whose free parameters are the absorption coefficient ua at each wavelength and two variables A and b which characterize the reduced scattering spectrum of the form u's = Alambda-b. We analyze our spectroscopic data using a nonlinear fitting algorithm to determine A, b, and ua at each wavelength independently; no prior knowledge of the absorption spectrum or of the sample's constituent absorbers is required. We have tested this method in tissue simulating phantoms composed of intralipid and the photosensitizer motexafin lutetium (MLu). The MLu absorption spectrum recovered from the phantoms agrees with that measured in clear solution, and ua at the MLu absorption peak varies linearly with concentration. The u's spectrum reported by the fit is in agreement with the known scattering coefficient of intralipid. We have applied this algorithm to spectroscopic data from human patients sensitized with MLu (2 mg kg 1) acquired before and after PDT. Before PDT, the absorption spectra we measure include the characteristic MLu absorption peak. Using our phantom data as a calibration, we have determined the pre-treatment MLu concentration to be approximately 2 to 8 mg kg-1. After PDT, the concentration is reduced to 1 to 2.5 mg kg-1, an indication of photobleaching induced by irradiation. In addition, absorption features corresponding to the oxygenated and deoxygenated forms of hemoglobin indicate a reduction in tissue oxygenation during treatment. PMID- 26146443 TI - Fabrication of the pinhole aperture for AdaptiSPECT. AB - AdaptiSPECT is a pre-clinical pinhole SPECT imaging system under final construction at the Center for Gamma-Ray Imaging. The system is designed to be able to autonomously change its imaging configuration. The system comprises 16 detectors mounted on translational stages to move radially away and towards the center of the field-of-view. The system also possesses an adaptive pinhole aperture with multiple collimator diameters and pinhole sizes, as well as the possibility to switch between multiplexed and non-multiplexed imaging configurations. In this paper, we describe the fabrication of the AdaptiSPECT pinhole aperture and its controllers. PMID- 26146439 TI - Early life environment and developmental immunotoxicity in inflammatory dysfunction and disease. AB - Components of the innate immune system such as macrophages and dendritic cells are instrumental in determining the fate of immune responses and are, also, among the most sensitive targets of early life environmental alterations including developmental immunotoxicity (DIT). DIT can impede innate immune cell maturation, disrupt tissue microenvironment, alter immune responses to infectious challenges, and disrupt regulatory responses. Dysregulation of inflammation, such as that observed with DIT, has been linked with an increased risk of chronic inflammatory diseases in both children and adults. In this review, we discuss the relationship between early-life risk factors for innate immune modulation and promotion of dysregulated inflammation associated with chronic inflammatory disease. The health risks from DIT-associated inflammation may extend beyond primary immune dysfunction to include an elevated risk of several later-life, inflammatory mediated diseases that target a wide range of physiological systems and organs. For this reason, determination of innate immune status should be an integral part of drug and chemical safety evaluation. PMID- 26146444 TI - A New Columnar CsI(Tl) Scintillator for iQID detectors. AB - A 1650 MUm thick columnar CsI(Tl) scintillator for upgrading iQID detectors, which is a high-resolution photon-counting gamma-ray and x-ray detector recently developed at the Center for Gamma-Ray Imaging (CGRI), has been studied in terms of sensitivity, spatial resolution and depth-of-interaction effects. To facilitate these studies, a new frame-parsing algorithm for processing raw event data is also proposed that has more degrees of freedom in data processing and can discriminate against a special kind of noise present in some low-cost intensifiers. The results show that in comparison with a 450 MUm-thickness columnar CsI(Tl) scintillator, the 1650 MUm thick CsI(Tl) scintillator provides more than twice the sensitivity at the expense of some spatial resolution degradation. The depth-of-interaction study also shows that event size and amplitude vary with scintillator thickness, which can assist in future detector simulations and 3D-interaction-position estimation. PMID- 26146445 TI - Lesion Insertion in Projection Domain for Computed Tomography Image Quality Assessment. AB - To perform task-based image quality assessment in CT, it is desirable to have a large number of realistic patient images with known diagnostic truth. One effective way to achieve this objective is to create hybrid images that combine patient images with simulated lesions. Because conventional hybrid images generated in the image-domain fails to reflect the impact of scan and reconstruction parameters on lesion appearance, this study explored a projection domain approach. Liver lesion models were forward projected according to the geometry of a commercial CT scanner to acquire lesion projections. The lesion projections were then inserted into patient projections (decoded from commercial CT raw data with the assistance of the vendor) and reconstructed to acquire hybrid images. To validate the accuracy of the forward projection geometry, simulated images reconstructed from the forward projections of a digital ACR phantom were compared to physically acquired ACR phantom images. To validate the hybrid images, lesion models were inserted into patient images and visually assessed. Results showed that the simulated phantom images and the physically acquired phantom images had great similarity in terms of HU accuracy and high contrast resolution. The lesions in the hybrid image had a realistic appearance and merged naturally into the liver background. In addition, the inserted lesion demonstrated reconstruction-parameter-dependent appearance. Compared to conventional image-domain approach, our method enables more realistic hybrid images for image quality assessment. PMID- 26146446 TI - Impact of Number of Repeated Scans on Model Observer Performance for a Low contrast Detection Task in CT. AB - Channelized Hotelling observer (CHO) has been validated against human observers for detection/classification tasks in clinical CT and shows encouraging correlations. However, the goodness of correlations depends on the number of repeated scans used in CHO to estimate the template and covariance matrices. The purpose of this study is to investigate how the number of repeated scans affects the CHO performance in predicting human observers. A phantom containing 21 low contrast objects (3 contrast levels and 7 sizes) was scanned on a 128-slice CT scanner at three dose levels. Each scan was repeated 100 times. Images were reconstructed using a filtered-backprojection kernel and a commercial iterative reconstruction method. For each dose level and reconstruction setting, the low contrast detectability, quantified with the area under receiver operating characteristic curve (Az), was calculated using a previously validated CHO. To determine the dependency of CHO performance on the number of repeated scans, the Az value was calculated for each object and dose/reconstruction setting using all 100 repeated scans. The Az values were also calculated using randomly selected subsets of the scans (from 10 to 90 scans with an increment of 10 scans). Using the Az from the 100 scans as the reference, the accuracy of Az from a smaller number of scans was determined. The minimum necessary number of scans was subsequently derived. For the studied signal-known-exactly detection task, results demonstrated that, the minimal number of scans required to accurately predict human observer performance depends on dose level, object size and contrast level, and channel filters. PMID- 26146447 TI - Association of FTO Mutations with Risk and Survival of Breast Cancer in a Chinese Population. AB - Recently, several studies have reported associations between fat mass and obesity associated (FTO) gene mutations and cancer susceptibility. But little is known about their association with risk and survival of breast cancer in Chinese population. The aim of this study is to examine whether cancer-related FTO polymorphisms are associated with risk and survival of breast cancer and BMI levels in controls in a Chinese population. We genotyped six FTO polymorphisms in a case-control study, including 537 breast cancer cases and 537 controls. FTO rs1477196 AA genotype had significant decreased breast cancer risk [odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.34-0.86] compared to GG genotype, and this association was only found in women with BMI < 24 kg/m(2) (OR = 0.41, 95% CI: 0.22-0.76); and rs16953002 AA genotype conferred significant increased breast cancer risk (OR = 1.80, 95% CI: 1.23-2.63) compared to GG genotype. Haplotype analysis showed that FTO TAC haplotype (rs9939609-rs1477196-rs1121980) had significant reduced breast cancer risk (OR = 0.76, 95% CI: 0.62-0.93) compared with TGC haplotype. But we failed to find any association between FTO polymorphisms and breast cancer survival. These findings suggest that variants in FTO gene may influence breast cancer susceptibility. PMID- 26146448 TI - First-Trimester Serum Acylcarnitine Levels to Predict Preeclampsia: A Metabolomics Approach. AB - OBJECTIVE: To expand the search for preeclampsia (PE) metabolomics biomarkers through the analysis of acylcarnitines in first-trimester maternal serum. METHODS: This was a nested case-control study using serum from pregnant women, drawn between 8 and 14 weeks of gestational age. Metabolites were measured using an UPLC-MS/MS based method. Concentrations were compared between controls (n = 500) and early-onset- (EO-) PE (n = 68) or late-onset- (LO-) PE (n = 99) women. Metabolites with a false discovery rate <10% for both EO-PE and LO-PE were selected and added to prediction models based on maternal characteristics (MC), mean arterial pressure (MAP), and previously established biomarkers (PAPPA, PLGF, and taurine). RESULTS: Twelve metabolites were significantly different between EO PE women and controls, with effect levels between -18% and 29%. For LO-PE, 11 metabolites were significantly different with effect sizes between -8% and 24%. Nine metabolites were significantly different for both comparisons. The best prediction model for EO-PE consisted of MC, MAP, PAPPA, PLGF, taurine, and stearoylcarnitine (AUC = 0.784). The best prediction model for LO-PE consisted of MC, MAP, PAPPA, PLGF, and stearoylcarnitine (AUC = 0.700). CONCLUSION: This study identified stearoylcarnitine as a novel metabolomics biomarker for EO-PE and LO PE. Nevertheless, metabolomics-based assays for predicting PE are not yet suitable for clinical implementation. PMID- 26146450 TI - Spiraling into History: A Molecular Phylogeny and Investigation of Biogeographic Origins and Floral Evolution for the Genus Costus. AB - Rapid radiations are notoriously difficult to resolve, yet understanding phylogenetic patterns in such lineages can be useful for investigating evolutionary processes associated with bursts of speciation and morphological diversification. Here we present an expansive molecular phylogeny of Costus L. (Costaceae Nakai) with a focus on the Neotropical species within the clade, sampling 47 of the known 51 Neotropical species and including five molecular markers for phylogenetic analysis (ITS, ETS, rps16, trnL-F, and CaM). We use the phylogenetic results to investigate shifts in pollination syndrome, with the intention of addressing potential mechanisms leading to the rapid radiation documented for this clade. Our ancestral reconstruction of pollination syndrome presents the first evidence in this genus of an evolutionary toggle in pollination morphologies, demonstrating both the multiple independent evolutions of ornithophily (bird pollination) as well as reversals to melittophily (bee pollination). We show that the ornithophilous morphology has evolved at least eight times independently with four potential reversals to melittophilous morphology, and confirm prior work showing that neither pollination syndrome defines a monophyletic lineage. Based on the current distribution for the Neotropical and African species, we reconstruct the ancestral distribution of the Neotropical clade as the Pacific Coast of Mexico and Central America. Our results indicate an historic dispersal of a bee-pollinated taxon from Africa to the Pacific Coast of Mexico/Central America, with subsequent diversification leading to the evolution of a bird-pollinated floral morphology in multiple derived lineages. PMID- 26146449 TI - Two-cationic 2-methylbenzothiazole derivatives as green light absorbed sensitizers in initiation of free radical polymerization. AB - N-Methylpyridinium esters derivatives of 2-methylbenzothiazole hemicyanine dyes photoinitiators/photosensitizers derived from N-propyl-3-[N-2 methylbenzothiazolo]-4-pyridyno phenylacetic acid ester diiodide and N-propyl-3 [N-2-me]thylbenzothiazolo]-4-pyridino diphenylacetic acid ester diiodide were synthesized and proposed as new photoinitiators of polymerization of 2-ethyl-(2 hydroxymethyl)-1,3-propanediol triacrylate under argon laser exposure at 514 nm. These compounds exhibit a strong absorption around 520 nm. The dye/borate salt, dye/borate salt/N-methoxypyridinium salt, dye/borate salt/diphenyliodonium salt, and dye/borate salt/1,3,5-triazine derivative combinations are very efficient in initiating of radical photopolymerization of triacrylate. Excellent polymerization profiles were obtained. The effect of both sensitizer and co initiator structure on the ability to initiate of free radical polymerization of photoinitiating systems was also presented. The mechanism was discussed for different multicomponent initiating systems. Graphical AbstractTwo-cationic 2 methylbenzothiazole derivatives as green light absorbed sensitizers in initiation of free radical polymerization. PMID- 26146451 TI - A Trait-State-Error Model of Adult Hassles Over Two Years: Magnitude, Sources, and Predictors of Stress Continuity. AB - There are stable individual differences in exposure to stressful circumstances over time. The current study employed a latent trait-state model to estimate the magnitude of that stability and its sources. Adults (N = 327; age M = 43.9 years, SD = 6.15) provided reports of hassles and depressive symptoms every three months for two years. A Trait-State-Error model suggested that 60% of the variance in self-reports of hassles was attributable to stable, between-persons factors. Of the remaining variance, 20% was attributable to an autoregressive factor and 20% was attributable to either unique state factors or error. Moreover, average depressive symptoms, family income, and family conflict reported at baseline were significant predictors of the stable trait factor. These findings suggest that adults' self-reports of stressful experiences show marked stability over time, and that this stability may have significant implications for understanding the occurrence and impact of stress. PMID- 26146452 TI - EVENT PREDICTION AND AFFECTIVE FORECASTING IN DEPRESSIVE COGNITION: USING EMOTION AS INFORMATION ABOUT THE FUTURE. AB - Depression is characterized by a bleak view of the future, but the mechanisms through which depressed mood is integrated into basic processes of future oriented cognition are unclear. We hypothesized that dysphoric individuals' predictions of what will happen in the future (likelihood estimation) and how the future will feel (affective forecasting) are attributable to individual differences in incorporating present emotion as judgment-relevant information. Dysphoric individuals (n = 77) made pessimistic likelihood estimates and blunted positive affective forecasts relative to controls (n = 84). These differences were mediated by dysphoric individuals' tendencies to rely on negative emotion as information more than controls-and on positive emotion less-independent of anhedonia. These findings suggest that (1) blunted positive affective forecasting is a distinctive component of depressive future-oriented cognition, and (2) future-oriented cognitive processes are linked not just to current emotional state, but also to individual variation in using that emotion as information. This role of individual differences elucidates basic mechanisms in future oriented cognition, and suggests routes for intervention on interrelated cognitive and affective processes in depression. PMID- 26146453 TI - The Roles and Needs of Families of Adolescents with ASD. AB - The transition of a student out of high school and into the adult world can be a stressful time for many families of high school students. This major life transition can be particularly challenging for students with ASD and their families. In this paper we first discuss the roles of families in the transition process for their son or daughter with ASD. Next, we present literature on the unique needs of families of adolescents with ASD during the transition to adulthood. Finally, we highlight current research on best practices for supporting transition-aged students and their families as well as discuss future directions for research and practice. PMID- 26146454 TI - Large-Scale Silica Overcoating of Gold Nanorods with Tunable Shell Thicknesses. AB - Gold nanorods (GNRs) overcoated with SiO2 are of interest for enhancing the shape stability of GNRs during photo-thermal heating, for further functionalization with silanes, and for biomedical applications. While methods have recently been developed for synthesizing GNRs on a large scale, SiO2 overcoating of GNRs is still conducted on a small reaction scale. Here, we report a method for large scale synthesis of SiO2-overcoated GNRs (SiO2-GNRs), which gives ~190 mg of SiO2 GNRs. SiO2 is deposited onto and encapsulates the cetyltrimethylammonium bromide (CTAB) coatings that stabilize GNRs by adding tetraethoxysilane (TEOS) via syringe pump. Control over the CTAB concentration is critically important for obtaining uniform overcoatings. Optical absorbance spectra of SiO2-GNRs closely resemble uncoated GNRs, which indicates overcoating of single rather than multiple GNRs and confirms that they remain well dispersed. By adjusting the reaction conditions, shells as thick as ~20 nm can be obtained. For thin shells (< 10 nm), addition of poly(ethylene glycol) silane (PEG-silane) at different times during the overcoating reaction allows facile control over the shell thickness, giving shells as thin as ~2 nm. The bulky PEG chain terminates further crosslinking and deposition of SiO2. PMID- 26146455 TI - Influence of land use on water quality in a tropical landscape: a multi-scale analysis. AB - There is a pressing need to understand the consequences of human activities, such as land transformations, on watershed ecosystem services. This is a challenging task because different indicators of water quality and yield are expected to vary in their responsiveness to large versus local-scale heterogeneity in land use and land cover (LUC). Here we rely on water quality data collected between 1977 and 2000 from dozens of gauge stations in Puerto Rico together with precipitation data and land cover maps to (1) quantify impacts of spatial heterogeneity in LUC on several water quality indicators; (2) determine the spatial scale at which this heterogeneity influences water quality; and (3) examine how antecedent precipitation modulates these impacts. Our models explained 30-58% of observed variance in water quality metrics. Temporal variation in antecedent precipitation and changes in LUC between measurements periods rather than spatial variation in LUC accounted for the majority of variation in water quality. Urbanization and pasture development generally degraded water quality while agriculture and secondary forest re-growth had mixed impacts. The spatial scale over which LUC influenced water quality differed across indicators. Turbidity and dissolved oxygen (DO) responded to LUC in large-scale watersheds, in-stream nitrogen concentrations to LUC in riparian buffers of large watersheds, and fecal matter content and in-stream phosphorus concentration to LUC at the sub-watershed scale. Stream discharge modulated impacts of LUC on water quality for most of the metrics. Our findings highlight the importance of considering multiple spatial scales for understanding the impacts of human activities on watershed ecosystem services. PMID- 26146456 TI - STOCHASTIC SOLUTIONS FOR FRACTIONAL WAVE EQUATIONS. AB - A fractional wave equation replaces the second time derivative by a Caputo derivative of order between one and two. In this paper, we show that the fractional wave equation governs a stochastic model for wave propagation, with deterministic time replaced by the inverse of a stable subordinator whose index is one half the order of the fractional time derivative. PMID- 26146457 TI - Effective treatment of alkaline Cr(VI) contaminated leachate using a novel Pd bionanocatalyst: Impact of electron donor and aqueous geochemistry. AB - Palladium catalysts offer the potential for the effective treatment of a variety of priority reducible pollutants in natural waters. In this study, microbially synthesized magnetite nanoparticles were functionalized with Pd(0), creating a highly reactive, magnetically recoverable, nano-scale catalyst (Pd-BnM). This was then investigated for the treatment of model Cr(VI) contaminated solutions at a range of pH values, and also alkaline Cr(VI) contaminated leachates from chromite ore processing residue (COPR); a contaminant issue of global concern. The sample of COPR used in this study was obtained from a site in Glasgow, UK, where extensive Cr(VI) contamination has been reported. In initial experiments Pd-BnM was supplied with H2 gas or formate as electron donors, and Cr(VI) removal from model synthetic solutions was quantified at various pH values (2-12). Effective removal was noted at neutral to environmentally relevant alkaline (pH 12) pH values, while the use of formate as an electron donor resulted in loss of performance under acidic conditions (pH 2). Reaction kinetics were then assessed with increasing Pd-BnM loading in both model pH 12 Cr(VI) solutions and the COPR leachate. When formate was used as the electron donor for Pd-BnM, to treat COPR leachate, there was significant inhibition of Cr(VI) removal. In contrast, a promotion of reaction rate, was observed when H2 was employed. Upon sustained reaction with model Cr(VI) solutions, in the presence of excess electron donor (formate or H2), appreciable quantities of Cr(VI) were removed before eventual inactivation of the catalyst. Faster onset of inactivation was reported in the COPR leachates, removing 4% and 64% of Cr(VI) observed from model Cr(VI) solutions, when formate and H2 were used as electron donors, respectively. XAS, TEM-EDX and XPS analysis of the catalysts that had been inactivated in the model solution, showed that the surface had an extensive covering of reduced Cr(III), most likely as a CrOOH phase. COPR reacted catalysts recorded a lower abundance of Cr(III) alongside a high abundance of the leachate components Ca and Si, implicating these elements in the faster onset of inactivation. PMID- 26146458 TI - High-resolution densitometry and elemental analysis of tropical wood. AB - KEY MESSAGE: Understanding the mobility and distribution of chemical elements in wood is necessary to apply dendrochemistry. Crystals are likely stable and could be used to analyze changes in nutrient supply. ABSTRACT: Dendrochemistry uses the variation in wood chemical composition to infer about past environmental conditions and possible effects on tree growth. Elemental or isotopic variation might also help to identify annual growth where tree rings are anatomically not distinct. However, most elements are-to a certain degree-mobile within wood and may be related to anatomical structures. Therefore, understanding what affects elemental distribution is important to make use of and critically assess the potential of dendrochemistry. We studied the variation of wood density and elements at high spatial resolution in wood of six species with anatomically distinct to rather indistinct tree rings from a Thai monsoon forest. Many elements had a higher concentration in parenchyma than in fiber cells, and the co variation of elements differed strongly between elements and also between species. Strong wood density changes along the ring boundary were found only in Melia azedarach. In all species, the X-ray images showed crystals. EDX spectra showed that these consist of calcium or silicon (in Chukrasia tabularis) as major elemental components. A high concentration of heavy metals (Fe, Cu and Zn) was found in Vitex peduncularis. We conclude that at least for the species studied the radial variation of elemental concentration is unlikely to reveal annual rings that anatomy could not. However, if elements in crystals are more stable than in cell walls or living protoplasts, analyzing the distribution of elements present in crystals may show environmental conditions that, in turn, influence crystal formation and are little known. PMID- 26146459 TI - Physical Feature Encoding and Word Recognition Abilities Are Altered in Children with Intractable Epilepsy: Preliminary Neuromagnetic Evidence. AB - Objective evaluation of language function is critical for children with intractable epilepsy under consideration for epilepsy surgery. The purpose of this preliminary study was to evaluate word recognition in children with intractable epilepsy by using magnetoencephalography (MEG). Ten children with intractable epilepsy (M/F 6/4, mean +/- SD 13.4 +/- 2.2 years) were matched on age and sex to healthy controls. Common nouns were presented simultaneously from visual and auditory sensory inputs in "match" and "mismatch" conditions. Neuromagnetic responses M1, M2, M3, M4, and M5 with latencies of ~100 ms, ~150 ms, ~250 ms, ~350 ms, and ~450 ms, respectively, elicited during the "match" condition were identified. Compared to healthy children, epilepsy patients had both significantly delayed latency of the M1 and reduced amplitudes of M3 and M5 responses. These results provide neurophysiologic evidence of altered word recognition in children with intractable epilepsy. PMID- 26146460 TI - Objectively Measured Physical Activity Is Associated with Brain Volumetric Measurements in Multiple Sclerosis. AB - BACKGROUND: Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS). PURPOSE: This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI) in MS. METHOD: 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV), normalized WM volume (NWMV), and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations (pr) controlling for demographic and clinical variables. RESULTS: Moderate-to-vigorous physical activity (MVPA) was significantly associated with NGMV (pr = 0.370, p < 0.05), NWMV (pr = 0.433, p < 0.01), hippocampus (pr = 0.499, p < 0.01), thalamus (pr = 0.380, p < 0.05), caudate (pr = 0.539, p < 0.01), putamen (pr = 0.369, p < 0.05), and pallidum (pr = 0.498, p < 0.01) volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. CONCLUSION: Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS. PMID- 26146461 TI - Cognitive and Functional Impairment in Stroke Survivors with Basilar Artery Occlusive Disease. AB - BACKGROUND: Despite growing literature on posterior vascular disease, specific information about the cognitive and functional profiles of patients with basilar artery occlusion disease (BAOD) is scarce. The aims of this study were (1) to compare the cognitive statuses of BAOD survivors versus healthy controls and (2) to correlate the functional capacity outcomes with the cognitive profiles of BAOD patients. METHODS: Comprehensive cognitive and functional assessments were carried out in 28 patients with BAOD and 27 age- and education level-matched healthy controls. RESULTS: Compared to matched controls, patients presented impairments in selective, sustained, and set-shifting attention, processing speed, visuospatial skills, mental flexibility, and monitoring rules. There were significant deficits in verbal episodic memory (immediate and delayed recall) and visuospatial episodic memory (immediate and delayed recall and recognition). Functional capacity outcomes were significantly related to the cognitive test results. Seventy-five percent of patients had a Modified Rankin Scale score of 0 or 1. CONCLUSIONS: Our results indicate good functional outcomes in a selected group of BAOD survivors, despite the presence of subnormal performance on some cognitive tests, including tests of attention, executive function, and long-term memory. PMID- 26146462 TI - The Assessment of Selected Bone and Cartilage Biomarkers in Psoriatic Patients from Poland. AB - BACKGROUND: Psoriasis is an inflammatory disease in which joints involvement may be insidious and difficult to detect. Bone and cartilage biomarkers may be helpful in screening patients with psoriasis for psoriatic arthritis (PsA). OBJECTIVES: To assess bone and cartilage serum biomarkers in psoriasis. Methods. The study was conducted in 2014 and included 61 psoriatic patients and 30 healthy individuals. In both groups, the serum concentrations of soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), cartilage oligomeric matrix protein (COMP), osteoprotegerin (OPG), and interleukin-20 (IL-20) were examined. Severity of skin lesions was assessed by Psoriasis Area and Severity Index (PASI), body surface area (BSA), and Physician Global Assessment (PGA) scores. RESULTS: The duration of psoriasis was from 1 year to 45 years. 22 patients suffered from concomitant PsA. The mean value of PASI was 23.1 +/- 12.0 and BSA was 27.6 +/- 20.6%. COMP, OPG, and IL-20 concentrations in psoriatic patients were significantly higher than in the control group. OPG/sRANKL ratio was significantly lower in PsA patients than in psoriatic patients without arthritis. CONCLUSIONS: Results of the conducted study suggest that COMP, OPG, IL-20, and OPG/sRANKL ratio may appear useful biomarkers of bone and cartilage involvement in psoriasis. PMID- 26146465 TI - EPSTI1 Is Involved in IL-28A-Mediated Inhibition of HCV Infection. AB - It has been reported that IFN-lambdas inhibit HCV replication in vitro. But the mechanisms of how IL-28A conducts antiviral activity and the functions of IL-28A induced ISGs (IFN-stimulated genes) are not fully understood. In this study, we found that IL-28A has the antiviral effect on HCV life cycle including viral replication, assembly, and release. IL-28A and IFN-alpha synergistically inhibit virus replication. EPSTI1 (epithelial-stromal interaction 1), one of IL-28A induced ISGs, plays a vital role in IL-28A-mediated antiviral activity. Furthermore, forced expression of EPSTI1 effectively inhibits HCV replication in the absence of interferon treatment, and knockdown of EPSTI1 contributes to viral enhancement. EPSTI1 can activate PKR promoter and induce several PKR-dependent genes, including IFN-beta, IFIT1, OAS1, and RNase L, which is responsible for EPSTI1-mediated antiviral activity. PMID- 26146463 TI - Therapeutic Potential of IL-17-Mediated Signaling Pathway in Autoimmune Liver Diseases. AB - Emerging evidence reveals that various cytokines and tissue microenvironments contribute to liver inflammation and autoimmunity, and IL-17 family is one of highlights acknowledged. Although the implication of IL-17 family in most common autoimmune diseases (such as psoriasis, inflammatory bowel disease, and rheumatoid arthritis) has been extensively characterized, the role of this critical family in pathophysiology of autoimmune liver diseases (AILD) still needs to be clarified. In the review, we look into the intriguing biology of IL 17 family and further dissect on the intricate role of IL-17-mediated pathway in AILD. Considering encouraging data from preclinical and clinical trials, IL-17 targeted therapy has shown promises in several certain autoimmune conditions. However, blocking IL-17-mediated pathway is just beginning, and more fully investigation and reflection are required. Taking together, targeting IL-17 mediated responses may open up new areas of potential clinical treatment for AILD. PMID- 26146466 TI - The Teenage Brain: Social Reorientation and the Adolescent Brain-The Role of Gonadal Hormones in the Male Syrian Hamster. AB - Maturation of social cognition and a gain in social proficiency are universal aspects of adolescent development that prepare individuals for adulthood. Social cognition involves the perception and interpretation of social cues, followed by the generation of a behavioral response. Social proficiency is acquired through the ability to make behavioral adaptations as one learns from social experience; increased social proficiency facilitates successful social interactions. In males, the neuroendocrine bases of these developmental changes involve both activational and organizational influences of testicular hormones. Using the male Syrian hamster as a model, this review provides evidence that social stimuli acquire rewarding properties during adolescence via activational effects of pubertal testosterone, whereas the adolescent gain in social proficiency depends on organizational actions of pubertal testosterone. PMID- 26146464 TI - Adaptive Immunity and Antigen-Specific Activation in Obesity-Associated Insulin Resistance. AB - Type 2 diabetes mellitus (T2D) is a metabolic disease that is strongly tied to obesity and often preceded by insulin resistance (IR). It has been established that chronic inflammation of hypertrophic adipose tissue depots in obese individuals leads to obesity-associated IR and is mediated by cells of the innate immune system, particularly macrophages. More recently, cells of the adaptive immune system, B and T lymphocytes, have also emerged as important regulators of glucose homeostasis, raising the intriguing possibility that antigen-driven immune responses play a role in disease. In this review, we critically evaluate the roles that various B and T cell subsets play in IR, and then we examine the data suggesting that antigen-driven mechanisms, such as antigen presentation and costimulation, may drive the activity of these lymphocytes. PMID- 26146467 TI - Molecular and cellular mechanisms of the inhibitory effects of ACE-2/ANG1-7/Mas axis on lung injury. AB - An established body of recent literature has demonstrated potent inhibitory effects of the angiotensin converting enzyme-2 (ACE-2)/ANG1-7/ Mas axis on acute lung injury and lung fibrogenesis. One of the mechanisms of this inhibition is the enzymatic action of ACE-2 to degrade its main substrate angiotensin (ANG) II, thereby reducing the injurious and profibrotic activities of this octapeptide. Another, potentially more important mechanism is the production by ACE-2 of the heptapeptide ANG1-7, which inhibits the actions of ANGII through its own receptor Mas, the product of the oncogene of the same name. Very recent efforts to define the molecular and cellular mechanisms of ANG1-7/Mas action have revealed a number of similar, but mechanistically distinct, pathways by which ANG1-7 and Mas act on various lung cell types to inhibit lung injury and fibrosis. In this review we summarize the beneficial actions of the ANG1-7/Mas pathway, specifically on lung cells in non-neoplastic lung injury. We also review the currently known downstream signaling mechanisms of the ANG1-7/Mas pathway in various lung cell types known to be key in acute injury and fibrogenesis. PMID- 26146468 TI - The Role of Preschool Relational and Physical Aggression in the Transition to Kindergarten: Links with Social-Psychological Adjustment. AB - RESEARCH FINDINGS: The transition to kindergarten has important ramifications for future achievement and psychosocial outcomes. Research suggests that physical aggression may be related to difficulty during school transitions, yet no studies to date have examined the role of relational aggression in these transitions. This paper examined how engagement in preschool physical and relational aggression predicted psychosocial adjustment during the kindergarten school year. Observations and teacher reports of aggression were collected in preschool, and kindergarten teachers reported on student-teacher relationship quality, child internalizing problems, and peer acceptance in kindergarten. Results suggested that preschool physical aggression predicted reduced peer acceptance and increased conflict with the kindergarten teacher. High levels of relational aggression, when not combined with physical aggression, were related to more positive transitions to kindergarten in the domains assessed. PRACTICE OR POLICY: These data lend support to the need for interventions among physically aggressive preschoolers to target not only concurrent behavior but also future aggression and adjustment in kindergarten. Thus, educators should work to encourage social influence in more prosocial ways amongst aggressive preschoolers. PMID- 26146469 TI - Parametrically guided estimation in nonparametric varying coefficient models with quasi-likelihood. AB - Varying coefficient models allow us to generalize standard linear regression models to incorporate complex covariate effects by modeling the regression coefficients as functions of another covariate. For nonparametric varying coefficients, we can borrow the idea of parametrically guided estimation to improve asymptotic bias. In this paper, we develop a guided estimation procedure for the nonparametric varying coefficient models. Asymptotic properties are established for the guided estimators and a method of bandwidth selection via bias-variance tradeoff is proposed. We compare the performance of the guided estimator with that of the unguided estimator via both simulation and real data examples. PMID- 26146470 TI - Pubertal Timing and Tempo: Associations With Childhood Maltreatment. AB - The present study examined pubertal timing and tempo in a sample of 445 adolescents (53% male), using both variable-centered (latent growth curve) and person-centered (latent class) approaches, to discern the pubertal development trajectories associated with the experience of maltreatment. Results from the variable-centered analyses indicated a slower initial tempo that increased later for boys who had experienced neglect. The person-centered results indicated three classes for boys that mainly differentiated tempo effects and two classes for girls primarily distinguishing timing differences. For girls, sexual abuse predicted membership in an earlier pubertal timing class. These findings enhance our knowledge of the variability in pubertal development as well as gender differences in maltreatment types that may alter pubertal timing and tempo. PMID- 26146471 TI - PHOTOLABILE A1-ADENOSINE RECEPTOR AGONISTS AS "CAGED" ELECTROPHYSIOLOGICAL PROBES. AB - 5'-Ether derivatives of the potent adenosine agonist N6-cyclopentyladenosine (CPA) were designed as "caged" ligands for the activation of A1-adenosine receptors following in situ photolysis. The synthesis involved a 2',3'-diol protection scheme using the acid labile ethoxymethynyl group. Generation of CPA was demonstrated chromatographically and in a bioassay measuring the inhibition of synaptic potentials in the rat hippocampus. PMID- 26146473 TI - Measurement Errors in Fluorescence Microscopy Image Registration. AB - Image registration is an important processing step in fluorescence microscopy, for example in tracking or super-resolution methods. Precision localization of single fluorescent molecules from a quantum limited photon detection process, subject to Gaussian readout noise, is key to the use of single molecule microscopy. It is therefore important to know the effect that registration has on the accuracy of localizing a single molecule. Here we demonstrate a suitable approach to image registration that accounts for point-wise errors in localizing the control points typically used in fluorescence microscopy. This allows expressions for the localization errors caused by the registration process to be derived, showing dependence on the number of control points and their associated photon counts. PMID- 26146472 TI - A Review of the Differences in Developmental, Psychiatric, and Medical Endophenotypes Between Males and Females with Autism Spectrum Disorder. AB - Autism spectrum disorder (ASD) is over four times more prevalent in males compared to females. Increased understanding of sex differences in ASD endophenotypes could add insight into possible etiologies and the assessment and management of the disorder. Consequently, the purpose of this review is to describe current literature regarding sex differences in the developmental, psychiatric, and medical endophenotypes of ASD in order to illustrate current knowledge and areas in need of further research. Our review found that repetitive behaviors and restricted interests are more common in males than females with ASD. Intellectual disability is more common in females than males with ASD. Attention to detail may be more common in males than females with ASD and epilepsy may be more common in females than males with ASD, although limited research in these areas prevent definitive conclusions from being drawn. There does not appear to be a sex difference in other developmental, psychiatric, and medical symptoms associated with ASD, or the research was contradictory or too sparse to establish a sex difference. Our review is unique in that it offers detailed discussion of sex differences in three major endophenotypes of ASD. Further research is needed to better understand why sex differences exist in certain ASD traits and to evaluate whether phenotypic sex differences are related to different pathways of development, assessment, and treatment of the disorder. PMID- 26146474 TI - Health Vlogs as Social Support for Chronic Illness Management. AB - Studies have shown positive impact of video blogs (vlogs) on patient education. However, we know little on how patient-initiated vlogs shape the relationships among vloggers and viewers. We qualitatively analyzed 72 vlogs on YouTube by users diagnosed with HIV, diabetes, or cancer and 1,274 comments posted to the vlogs to understand viewers' perspectives on the vlogs. We found that the unique video medium allowed intense and enriched personal and contextual disclosure to the viewers, leading to strong community-building activities and social support among vloggers and commenters, both informationally and emotionally. Furthermore, the unique communication structure of the vlogs allowed ad hoc small groups to form, which showed different group behavior than typical text-based social media, such as online communities. We provide implications to the Health Care Industry (HCI) community on how future technologies for health vlogs could be designed to further support chronic illness management. PMID- 26146475 TI - Sparse PDF Volumes for Consistent Multi-Resolution Volume Rendering. AB - This paper presents a new multi-resolution volume representation called sparse pdf volumes, which enables consistent multi-resolution volume rendering based on probability density functions (pdfs) of voxel neighborhoods. These pdfs are defined in the 4D domain jointly comprising the 3D volume and its 1D intensity range. Crucially, the computation of sparse pdf volumes exploits data coherence in 4D, resulting in a sparse representation with surprisingly low storage requirements. At run time, we dynamically apply transfer functions to the pdfs using simple and fast convolutions. Whereas standard low-pass filtering and down sampling incur visible differences between resolution levels, the use of pdfs facilitates consistent results independent of the resolution level used. We describe the efficient out-of-core computation of large-scale sparse pdf volumes, using a novel iterative simplification procedure of a mixture of 4D Gaussians. Finally, our data structure is optimized to facilitate interactive multi resolution volume rendering on GPUs. PMID- 26146476 TI - Medication Adherence and HIV Symptom Distress in Relation to Panic Disorder Among HIV-Positive Adults Managing Opioid Dependence. AB - Panic disorder (PD) occurs at greater rates among those with HIV compared to those without HIV. Rates of PD may be elevated among those with opioid dependence (persons who inject drugs, PWID). Persons with HIV experience common bodily symptoms as a result of the disease and these symptoms overlap with those of PD which may contribute to a "fear of fear" cycle present in PD. HIV-positive, PWID represent an at-risk population in terms of poor medication adherence. HIV symptoms and HIV medication side-effects commonly overlap with panic symptoms and may affect HIV medication adherence. The aim of this investigation was to examine the impact of PD on HIV-related symptom distress and HIV medication adherence in HIV-positive adults (N = 131) in treatment for opioid use. Those with a diagnosis of PD evidenced greater levels of HIV symptom distress and lower levels of medication adherence than those without current PD. Results highlight the clinical importance of assessing for and treating PD among individuals with HIV that are prescribed antiretroviral therapy. Future work would benefit from examining observed associations longitudinally and identifying potential mechanisms involved. PMID- 26146477 TI - Valuable Orientations Capture Attention. AB - Visual attention has long been known to be drawn to stimuli that are physically salient or congruent with task-specific goals. Several recent studies have shown that attention is also captured by stimuli that are neither salient nor task relevant, but that are rendered in a color that has previously been associated with reward. We investigated whether another feature dimension-orientation-can be associated with reward via learning and thereby elicit value-driven attentional capture. In a training phase, participants received a monetary reward for identifying the color of Gabor patches exhibiting one of two target orientations. A subsequent test phase in which no reward was delivered required participants to search for Gabor patches exhibiting one of two spatial frequencies (orientation was now irrelevant to the task). Previously rewarded orientations robustly captured attention. We conclude that reward learning can imbue features other than color-in this case, specific orientations-with persistent value. PMID- 26146478 TI - Mesenchymal Chondrosarcoma in Children and Young Adults: A Single Institution Retrospective Review. AB - Background. Mesenchymal chondrosarcoma is an aggressive, uncommon histologic entity arising in bone and soft tissues. We reviewed our institutional experience with this rare diagnosis. Methods. We conducted a retrospective chart review on patients with mesenchymal chondrosarcoma over a 24-year period. Clinicopathologic and radiographic features were reviewed. Results. Twelve patients were identified. Nine were females; median age was 14.5 years (1.2-19.7 years). The most common site was the head/neck (7/12). Disease was localized in 11/12 patients (one with lung nodules). Six with available tissue demonstrated NCOA2 rearrangement by FISH. Six underwent upfront surgical resection, and six received neoadjuvant therapy (2 chemotherapy alone and 4 chemotherapy and radiation). All patients received adjuvant chemotherapy (most commonly ifosfamide/doxorubicin) and/or radiation (median dose 59.4 Gy). At a median follow-up of 4.8 years, 5 year disease-free survival and overall survival were 68.2% (95% CI 39.8%, 96.6%) and 88.9% (95% CI 66.9%, 100%). Two patients had distant recurrences at 15 and 42 months, respectively. Conclusion. Aggressive surgical resection of mesenchymal chondrosarcoma with chemoradiotherapy yields excellent local control and may reduce likelihood of late recurrence. Characterization of downstream targets of the HEY1-NCOA2 fusion protein, xenograft models, and drug screening are needed to identify novel therapeutic strategies. PMID- 26146479 TI - Bilingual children show an advantage in controlling verbal interference during spoken language comprehension. AB - Studies measuring inhibitory control in the visual modality have shown a bilingual advantage in both children and adults. However, there is a lack of developmental research on inhibitory control in the auditory modality. This study compared the comprehension of active and passive English sentences in 7-10 years old bilingual and monolingual children. The task was to identify the agent of a sentence in the presence of verbal interference. The target sentence was cued by the gender of the speaker. Children were instructed to focus on the sentence in the target voice and ignore the distractor sentence. Results indicate that bilinguals are more accurate than monolinguals in comprehending syntactically complex sentences in the presence of linguistic noise. This supports previous findings with adult participants (Filippi, Leech, Thomas, Green & Dick, 2012). We therefore conclude that the bilingual advantage in interference control begins early in life and is maintained throughout development. PMID- 26146480 TI - Solving ptychography with a convex relaxation. AB - Ptychography is a powerful computational imaging technique that transforms a collection of low-resolution images into a high-resolution sample reconstruction. Unfortunately, algorithms that currently solve this reconstruction problem lack stability, robustness, and theoretical guarantees. Recently, convex optimization algorithms have improved the accuracy and reliability of several related reconstruction efforts. This paper proposes a convex formulation of the ptychography problem. This formulation has no local minima, it can be solved using a wide range of algorithms, it can incorporate appropriate noise models, and it can include multiple a priori constraints. The paper considers a specific algorithm, based on low-rank factorization, whose runtime and memory usage are near-linear in the size of the output image. Experiments demonstrate that this approach offers a 25% lower background variance on average than alternating projections, the ptychographic reconstruction algorithm that is currently in widespread use. PMID- 26146481 TI - Beyond Group-Threat: Temporal Dynamics of International Migration and Linkages to Anti-Foreigner Sentiment. AB - Prior research on the association between country-level patterns of international migration and anti-foreigner sentiment shows that larger foreign-born concentrations increase perceptions of threat among native-born individuals in receiving countries, which, in turn, give rise to exclusionary preferences. While recent work has assembled a list of limiting conditions that shape the strength of this association, I argue that these efforts are premature because they are based on a narrow way of conceptualising and measuring international migration. In contrast to concepts and measures privileging the size of the foreign-born population in receiving countries, I draw from other literatures highlighting the temporal dynamics of migration. In considering the role of the temporal dynamics of international migration in explaining variation in anti-foreigner sentiment, the question is whether and how the temporal stability of the foreign-born population in receiving countries matters. My results suggest that it does. The size and temporal stability of the foreign-born population play opposing roles in aggravating and ameliorating anti-foreigner sentiment, respectively, with each operating via different pathways at the individual level. My work thus breaks new ground by challenging existing theoretical constructs and operationalisations in the group-threat literature. PMID- 26146482 TI - Iron(II)-Catalyzed Asymmetric Epoxidation of Trisubstituted alpha,beta Unsaturated Esters. AB - An asymmetric epoxidation of trisubstituted alpha,beta-unsaturated esters is described. The oxidation utilizes a pseudo-C2-symmetric iron(II) catalyst [Fe(L*)2(CH3CN)(OTf)](OTf) and peracetic acid as oxidant, yielding the alpha,beta epoxyesters in high enantiomeric purity (up to 99% ee). PMID- 26146485 TI - Patterns of contraceptive use among Mexican-origin women. AB - BACKGROUND: Mexican women in the United States (US) have higher rates of fertility compared to other ethnic groups and women in Mexico. Whether variation in women's access to family planning services or patterns of contraceptive use contributes to this higher fertility has received little attention. OBJECTIVE: We explore Mexican women's contraceptive use, taking into account women's place in the reproductive life course. METHODS: Using nationally representative samples from the US (National Survey of Family Growth) and Mexico (Encuesta National de la Dinamica Demografica), we compared the parity-specific frequency of contraceptive use and fertility intentions for non-migrant women, foreign-born Mexicans in the US, US-born Mexicans, and whites. RESULTS: Mexican women in the US were less likely to use IUDs and more likely to use hormonal contraception than women in Mexico. Female sterilization was the most common method among higher parity women in both the US and Mexico, however, foreign-born Mexicans were less likely to be sterilized, and the least likely to use any permanent contraceptive method. Although foreign-born Mexicans were slightly less likely to report that they did not want more children, differences in method use remained after controlling for women's fertility intentions. CONCLUSION: At all parities, foreign-born Mexicans used less effective methods. These findings suggest that varying access to family planning services may contribute to variation in women's contraceptive use. COMMENTS: Future studies are needed to clarify the extent to which disparities in fertility result from differences in contraceptive access. PMID- 26146486 TI - The reliability of in-home measures of height and weight in large cohort studies: Evidence from Add Health. AB - BACKGROUND: With the emergence of obesity as a global health issue an increasing number of major demographic surveys are collecting measured anthropometric data. Yet little is known about the characteristics and reliability of these data. OBJECTIVES: We evaluate the accuracy and reliability of anthropometric data collected in the home during Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health), compare our estimates to national standard, clinic-based estimates from the National Health and Nutrition Examination Survey (NHANES) and, using both sources, provide a detailed anthropometric description of young adults in the United States. METHODS: The reliability of Add Health in-home anthropometric measures was estimated from repeat examinations of a random subsample of study participants. A digit preference analysis evaluated the quality of anthropometric data recorded by field interviewers. The adjusted odds of obesity and central obesity in Add Health vs. NHANES were estimated with logistic regression. RESULTS: Short-term reliabilities of in-home measures of height, weight, waist and arm circumference as well as derived body mass index (BMI, kg/m2)-were excellent. Prevalence of obesity (37% vs. 29%) and central obesity (47% vs. 38%) was higher in Add Health than in NHANES while socio-demographic patterns of obesity and central obesity were comparable in the two studies. CONCLUSIONS: Properly trained non-medical field interviewers can collect reliable anthropometric data in a nationwide, home visit study. This national cohort of young adults in the United States faces a high risk of early-onset chronic disease and premature mortality. PMID- 26146484 TI - Age, education, and earnings in the course of Brazilian development: does composition matter? AB - BACKGROUND: The impacts of shifts in the age distribution of the working-age population have been studied in relation to the effect of the baby boom generation on the earnings of different cohorts in the U.S. However, this topic has received little attention in the context of the countries of Asia and Latin America, which are now experiencing substantial shifts in their age-education distributions. OBJECTIVE: In this analysis, we estimate the impact of the changing relative size of the adult male population, classified by age and education groups, on the earnings of employed men living in 502 Brazilian local labor markets during four time periods between 1970 and 2000. METHODS: Taking advantage of the huge variation across Brazilian local labor markets and demographic census micro-data, we used fixed effects models to demonstrate that age education group size depresses earnings. RESULTS: These effects are more detrimental among age-education groups with higher education, but they are becoming less negative over time. The decrease in the share of workers with the lowest level of education has not led to gains in the earnings of these workers in recent years. CONCLUSIONS: These trends might be a consequence of technological shifts and increasing demand for labor with either education or experience. Compositional shifts are influential, which suggests that this approach could prove useful in studying this central problem in economic development. PMID- 26146487 TI - Understanding DNA Repair in Hyperthermophilic Archaea: Persistent Gaps and Other Reasons to Focus on the Fork. AB - Although hyperthermophilic archaea arguably have a great need for efficient DNA repair, they lack members of several DNA repair protein families broadly conserved among bacteria and eukaryotes. Conversely, the putative DNA repair genes that do occur in these archaea often do not generate the expected phenotype when deleted. The prospect that hyperthermophilic archaea have some unique strategies for coping with DNA damage and replication errors has intellectual and technological appeal, but resolving this question will require alternative coping mechanisms to be proposed and tested experimentally. This review evaluates a combination of four enigmatic properties that distinguishes the hyperthermophilic archaea from all other organisms: DNA polymerase stalling at dU, apparent lack of conventional NER, lack of MutSL homologs, and apparent essentiality of homologous recombination proteins. Hypothetical damage-coping strategies that could explain this set of properties may provide new starting points for efforts to define how archaea differ from conventional models of DNA repair and replication fidelity. PMID- 26146488 TI - RB mutation and RAS overexpression induce resistance to NK cell-mediated cytotoxicity in glioma cells. AB - Several theories aim to explain the malignant transformation of cells, including the mutation of tumor suppressors and proto-oncogenes. Deletion of Rb (a tumor suppressor), overexpression of mutated Ras (a proto-oncogene), or both, are sufficient for in vitro gliomagenesis, and these genetic traits are associated with their proliferative capacity. An emerging hallmark of cancer is the ability of tumor cells to evade the immune system. Whether specific mutations are related with this, remains to be analyzed. To address this issue, three transformed glioma cell lines were obtained (Rb(-/-), Ras(V12), and Rb(-/-)/Ras(V12)) by in vitro retroviral transformation of astrocytes, as previously reported. In addition, Ras(V12) and Rb(-/-)/Ras(V12) transformed cells were injected into SCID mice and after tumor growth two stable glioma cell lines were derived. All these cells were characterized in terms of Rb and Ras gene expression, morphology, proliferative capacity, expression of MHC I, Rae1delta, and Rae1alphabetagammadeltaepsilon, mult1, H60a, H60b, H60c, as ligands for NK cell receptors, and their susceptibility to NK cell-mediated cytotoxicity. Our results show that transformation of astrocytes (Rb loss, Ras overexpression, or both) induced phenotypical and functional changes associated with resistance to NK cell mediated cytotoxicity. Moreover, the transfer of cell lines of transformed astrocytes into SCID mice increased resistance to NK cell-mediated cytotoxicity, thus suggesting that specific changes in a tumor suppressor (Rb) and a proto oncogene (Ras) are enough to confer resistance to NK cell-mediated cytotoxicity in glioma cells and therefore provide some insight into the ability of tumor cells to evade immune responses. PMID- 26146490 TI - OpenMM: A Hardware Independent Framework for Molecular Simulations. AB - The wide diversity of computer architectures today requires a new approach to software development. OpenMM is a framework for molecular mechanics simulations, allowing a single program to run efficiently on a variety of hardware platforms. PMID- 26146489 TI - Unlocking truths of gamma-secretase in Alzheimer's disease: what is the translational potential? AB - Considerable evidence, particularly from genetics, points to the aggregation prone amyloid beta-peptide as a pathogenic entity in Alzheimer's disease. Hence, the proteases that produce this peptide from its precursor protein have been prime targets for the development of potential therapeutics. One of these proteases, gamma-secretase, has been a particular focus. Many inhibitors and modulators of this membrane-embedded protease complex have been identified, with some brought into late-stage clinical trials, where they have spectacularly failed. The reasons for these failures will be discussed, along with recent findings on the mechanism of gamma-secretase and of Alzheimer-causing mutations that may suggest new strategies for targeting this enzyme. PMID- 26146492 TI - Latent Feature Decompositions for Integrative Analysis of Multi-Platform Genomic Data. AB - Increased availability of multi-platform genomics data on matched samples has sparked research efforts to discover how diverse molecular features interact both within and between platforms. In addition, simultaneous measurements of genetic and epigenetic characteristics illuminate the roles their complex relationships play in disease progression and outcomes. However, integrative methods for diverse genomics data are faced with the challenges of ultra-high dimensionality and the existence of complex interactions both within and between platforms. We propose a novel modeling framework for integrative analysis based on decompositions of the large number of platform-specific features into a smaller number of latent features. Subsequently we build a predictive model for clinical outcomes accounting for both within- and between-platform interactions based on Bayesian model averaging procedures. Principal components, partial least squares and non-negative matrix factorization as well as sparse counterparts of each are used to define the latent features, and the performance of these decompositions is compared both on real and simulated data. The latent feature interactions are shown to preserve interactions between the original features and not only aid prediction but also allow explicit selection of outcome-related features. The methods are motivated by and applied to a glioblastoma multiforme data set from The Cancer Genome Atlas to predict patient survival times integrating gene expression, microRNA, copy number and methylation data. For the glioblastoma data, we find a high concordance between our selected prognostic genes and genes with known associations with glioblastoma. In addition, our model discovers several relevant cross-platform interactions such as copy number variation associated gene dosing and epigenetic regulation through promoter methylation. On simulated data, we show that our proposed method successfully incorporates interactions within and between genomic platforms to aid accurate prediction and variable selection. Our methods perform best when principal components are used to define the latent features. PMID- 26146491 TI - Promotion of Well-Being in Person-Centered Mental Health Care. AB - An understanding of the mechanisms of personality development provides a systematic way to promote health as an integrated state of physical, mental, social, and spiritual well-being. Individual differences in personality are causal antecedents of the full range of psychopathology. The maturation with integration of personality appears to be an important mechanism by which diverse modalities of treatment promote wellness and reduce illness. First, the authors review the relationship between personality and a wide range of psychiatric disorders. Second, the authors evaluate the impact of character structure on a wide range of measures of well-being, including positive emotions, negative emotions, life satisfaction, perceived social support, and perceived health. Third, the authors describe a practical and inexpensive clinical method for facilitating the maturation and integration of personality based on an understanding of the processes of human thought, which underlie changes in personality and well-being. PMID- 26146493 TI - Machine Learning of Parameters for Accurate Semiempirical Quantum Chemical Calculations. AB - We investigate possible improvements in the accuracy of semiempirical quantum chemistry (SQC) methods through the use of machine learning (ML) models for the parameters. For a given class of compounds, ML techniques require sufficiently large training sets to develop ML models that can be used for adapting SQC parameters to reflect changes in molecular composition and geometry. The ML-SQC approach allows the automatic tuning of SQC parameters for individual molecules, thereby improving the accuracy without deteriorating transferability to molecules with molecular descriptors very different from those in the training set. The performance of this approach is demonstrated for the semiempirical OM2 method using a set of 6095 constitutional isomers C7H10O2, for which accurate ab initio atomization enthalpies are available. The ML-OM2 results show improved average accuracy and a much reduced error range compared with those of standard OM2 results, with mean absolute errors in atomization enthalpies dropping from 6.3 to 1.7 kcal/mol. They are also found to be superior to the results from specific OM2 reparameterizations (rOM2) for the same set of isomers. The ML-SQC approach thus holds promise for fast and reasonably accurate high-throughput screening of materials and molecules. PMID- 26146494 TI - M13 Bacteriophage-Based Self-Assembly Structures and Their Functional Capabilities. AB - Controlling the assembly of basic structural building blocks in a systematic and orderly fashion is an emerging issue in various areas of science and engineering such as physics, chemistry, material science, biological engineering, and electrical engineering. The self-assembly technique, among many other kinds of ordering techniques, has several unique advantages and the M13 bacteriophage can be utilized as part of this technique. The M13 bacteriophage (Phage) can easily be modified genetically and chemically to demonstrate specific functions. This allows for its use as a template to determine the homogeneous distribution and percolated network structures of inorganic nanostructures under ambient conditions. Inexpensive and environmentally friendly synthesis can be achieved by using the M13 bacteriophage as a novel functional building block. Here, we discuss recent advances in the application of M13 bacteriophage self-assembly structures and the future of this technology. PMID- 26146495 TI - Stable Isotope Resolved Metabolomics Analysis of Ribonucleotide and RNA Metabolism in Human Lung Cancer Cells. AB - We have developed a simple NMR-based method to determine the turnover of nucleotides and incorporation into RNA by stable isotope resolved metabolomics (SIRM) in A549 lung cancer cells. This method requires no chemical degradation of the nucleotides or chromatography. During cell growth, the free ribonucleotide pool is rapidly replaced by de novo synthesized nucleotides. Using [U-13C] glucose and [U-13C,15N]-glutamine as tracers, we showed that virtually all of the carbons in the nucleotide riboses were derived from glucose, whereas glutamine was preferentially utilized over glucose for pyrimidine ring biosynthesis, via the synthesis of Asp through the Krebs cycle. Incorporation of the glutamine amido nitrogen into the N3 and N9 positions of the purine rings was also demonstrated by proton-detected 15N NMR. The incorporation of 13C from glucose into total RNA was measured and shown to be a major sink for the nucleotides during cell proliferation. This method was applied to determine the metabolic action of an anti-cancer selenium agent (methylseleninic acid or MSA) on A549 cells. We found that MSA inhibited nucleotide turnover and incorporation into RNA, implicating an important role of nucleotide metabolism in the toxic action of MSA on cancer cells. PMID- 26146496 TI - The risk and burden of smoking related heart disease mortality among young people in the United States. AB - PURPOSE: Although cigarette smoking remains the most common risk factor for heart disease among the young, few studies have explored the relationship of smoking with heart disease mortality risk among young people. This prospective study assesses the risk and burden of all heart disease (HD) and coronary heart disease (CHD) mortality associated with smoking among younger adults from a nationally representative sample of the United States. METHOD: National Health Interview Survey respondents' data from 1997-2004 were linked to their death records through 2006. The analyses were restricted to individuals 18 to 44 years of age during follow up (n = 121,284). Cox proportional hazard ratios (HR) were estimated with adjustment for sample weights and design effects. Attributable fractions (AF) of smoking were calculated. RESULTS: After controlling for age, race, body mass index, history of hypertension and diabetes, and leisure time physical activity, current smoking related CHD mortality HR was 14.6 [95 % confidence interval or CI, 3.3-64.9] for females and 3.6 [95 % CI, 1.2-10.4] for males. The HR for all HD mortality was 3.1 [95 % CI, 1.3-7.6] for females and 2.4 [95 % CI, 1.2-4.7] for males. The AF of smoking for CHD deaths for female and male were 0.58 and 0.54 respectively. The AF of all HD mortality was 0.31 for male and 0.32 for female. The mean estimates of all HD deaths attributable to smoking during 1997-2006 among this age group were 52,214, of which 45,147 were CHD deaths. CONCLUSION: Even after adjustment for multiple risk factors and without addressing passive smoking, our result showed a strong relationship between smoking and HD and CHD mortality among young adults that is likely causal. PMID- 26146497 TI - Design and Control of a Pneumatically Actuated Transtibial Prosthesis. AB - This paper presents the design and control of a pneumatically actuated transtibial prosthesis, which utilizes a pneumatic cylinder-type actuator to power the prosthetic ankle joint to support the user's locomotion. The pneumatic actuator has multiple advantages over the traditional electric motor, such as light weight, low cost, and high power-to-weight ratio. The objective of this work is to develop a compact and lightweight transtibial prosthesis, leveraging the multiple advantages provided by this highly competitive actuator. In this paper, the design details of the prosthesis are described, including the determination of performance specifications, the layout of the actuation mechanism, and the calculation of the torque capacity. Through the authors' design calculation, the prosthesis is able to provide sufficient range of motion and torque capacity to support the locomotion of a 75 kg individual. The controller design is also described, including the underlying biomechanical analysis and the formulation of the finite-state impedance controller. Finally, the human subject testing results are presented, with the data indicating that the prosthesis is able to generate a natural walking gait and sufficient power output for its amputee user. PMID- 26146498 TI - Fecal Microbiota Transplantation Improves the Quality of Life in Patients with Inflammatory Bowel Disease. AB - Introduction. To determine the effect of fecal microbiota transplantation (FMT) on quality of life (QoL) in patients with inflammatory bowel disease (IBD). Methods. Fourteen IBD patients, including 11 Ulcerative colitis (UC) and 3 Crohn's disease (CD), were treated with FMT via colonoscopy or nasojejunal tube infusion. QoL was measured by IBD Questionnaire (IBDQ). Disease activity and IBDQ were evaluated at enrollment and four weeks after treatment. Patients' attitude concerning the treatment was also investigated. Results. One patient was excluded due to intolerance. All the other patients finished the study well. Mean Mayo score in UC patients decreased significantly (5.80 +/- 1.87 versus 1.50 +/- 1.35, P < 0.01). Mean IBDQ scores of both UC and CD patients increased (135.50 +/- 27.18 versus 177.30 +/- 20.88, P = 0.00063, and 107.33 +/- 9.45 versus 149.00 +/- 20.07, P = 0.024) four weeks after fecal microbiota transplantation. There was no correlation between the IBDQ score and Mayo score before and after FMT. Patients refused to take FMT as treatment repeatedly in a short time. Conlusions. Fecal microbiota transplantation improves quality of life significantly in patients with inflammatory bowel disease. PMID- 26146499 TI - Shear Wave Velocity: A New Quantitative Index to Estimate the Status of Thyroid in Diffuse Thyroid Disease. AB - Objective. The purpose of the study was to assess the application value of VTQ in DTD. Research Design and Methods. Thirty healthy subjects and 74 DTD patients were involved. The thyroid stiffness, which was expressed by SWV, was measured by VTQ and compared between the patients and healthy people. The relationship between SWV and thyroid serological indexes was also analyzed. Results. The thyroid SWVs of DTD patients were higher than those of the healthy (2.56 +/- 1.33 m/s versus 1.74 +/- 0.16 m/s, P = 0.011). There was no significant difference between the thyroid SWVs in GD and HT patients (P = 0.168). The SWVs in patients with GD and HT were both higher than those of the healthy (P < 0.05). The area under the ROC curve was 0.938 for SWV to distinguish between DTD and healthy thyroid. With a cutoff value of 2.02 m/s, the sensitivity and specificity were 81.12% and 100.00%, respectively. Additionally, we found a positive liner correlation between thyroid SWV and TSH in DTD patients (P < 0.001). Conclusion. SWV is a good indicator of the thyroid tissue stiffness, which might be considered helpful in screening DTD. What is more, SWV might have a potential in assessing the thyroid function. PMID- 26146500 TI - Interdental Papilla Length and the Perception of Aesthetics in Asymmetric Situations. AB - The purpose of the study was to determine if there was a difference in the perception of aesthetics, by dental specialty, using computer assisted asymmetric alteration of the papilla length in the aesthetic zone with an apical alteration of the contact point of the clinical crowns. Standardized photographs were presented to sixty-five randomly selected dentists from New York University College of Dentistry on a computer screen for evaluation. Then, the dental professionals were asked to rate the smile in each picture. Control and experiment photographs were used. Data was analyzed using the statistical package SPSS version 21 and one-way ANOVA. The perception of esthetics depends on the dental professional specialty; results provide evidence that asymmetric deficiency in papilla length of 2 mm or more is perceived as "unattractive" by the dental specialists. PMID- 26146501 TI - Dental Implant Supported Restorations Improve Quality of Life in Osteoporotic Women. AB - Introduction. The aim of this study is to compare the quality of life (QoL) in partially edentulous osteoporotic women who have missing teeth restored with dental implant retained restorations with those who do not and, secondarily, to report the rate of osteonecrosis in this sample. Methods. 237 participants completed the Utian QoL survey, a 23-question document measuring across psychosocial domains of well-being including occupational, health, emotional, and sexual domains which together contribute to an overall score. The subset of participants having dental implant supported prosthesis (64) was compared to the subset having nonimplant supported fixed restorations (47), the subset having nonimplant supported removable restorations (60), and the subset having no restoration of missing teeth (66). Results. ANOVA showed significant difference in all QoL domains between the four subsets (p < 0.05). Although 134 reported oral bisphosphonate and 51 reported IV bisphosphonate use, no signs of ONJ were identified in any participants. Conclusion. These findings show implant retained oral rehabilitation has a statistically significant impact over nonimplant and traditional fixed restorations, removable restorations, and no restoration of missing teeth in far reaching areas including occupational, health, emotional, sexual, and overall QoL. These findings also support future examination of psychosocial outcomes associated with oral rehabilitation and the incorporation of oral health into women's health promotion. PMID- 26146502 TI - Stress Induced Cardiomyopathy with Midventricular Ballooning: A Rare Variant. AB - Stress cardiomyopathy (SCM) also referred to as the "broken heart syndrome" is a condition in which intense emotional or physical stress can cause fulminant and reversible cardiac muscle weakness. SCM most commonly involves the apical segment of left ventricle but newer and rare variants have recently been seen reported. We here report a case of rare midventricular variant of stress related cardiomyopathy. A 72-year-old female with past medical history, only significant for SVT, presented with an episode of severe substernal chest pain while hiking with her husband. She felt a significant heaviness in her chest and was short of breath. During her hospitalization she was found to have positive cardiac enzymes. EKG showed 1 mm downsloping ST segment changes. Ventriculogram during left heart catheterization revealed dyskinetic midventricle. Patient was diagnosed with midventricular SCM. The patient was placed on ACE inhibitor and beta-blocker and discharged in a well-compensated state. We suggest identifying these patients by standard lab testing, electrocardiography, echocardiography, and left heart coronary angiography and ventriculography. Management of this unique entity is similar to the other variants with close observation and treatment of accompanying heart failure, valvular dysfunction, and any arrhythmias that may develop. PMID- 26146503 TI - Acute Renal Failure due to Leukaemic Infiltration in Chronic Lymphocytic Leukaemia. AB - Chronic lymphocytic leukemia (CLL) is a malignancy characterized by clonal proliferation and accumulation of B lymphocytes. Although leukaemic infiltration of the kidney is well recognized in CLL, acute renal failure (ARF) due to leukaemic infiltration is extremely rare. Here we present a case of ARF as the initial manifestation of CLL. The diagnosis was made by a kidney biopsy. Treatment with cyclophosphamide and prednisolone resulted in a completely improved renal function. PMID- 26146505 TI - From phenotype to mechanism after zebrafish small molecule screens. AB - Small molecules screens conducted with living zebrafish have become a commonly practiced technique for small molecule discovery. Embryonic and larval zebrafish exhibit an almost limitless range of phenotypes, from the cellular to the organismal. Consequently, small molecule screens can be designed to discover compounds modifying any of these phenotypes. The compounds discovered by zebrafish screens pose unique challenges for target identification, but the zebrafish also provides several powerful approaches for identifying targets and determining mechanisms of action. Four major approaches have been used successfully, including methods based on comparison of chemical structures, genetic phenocopy, pharmacologic phenocopy, and compound affinity. These approaches will continue to facilitate target identification for compounds from zebrafish small molecule screens, and more importantly, to reveal their mechanisms of action. PMID- 26146504 TI - An Update on Ocular Surface Epithelial Stem Cells: Cornea and Conjunctiva. AB - The human ocular surface (front surface of the eye) is formed by two different types of epithelia: the corneal epithelium centrally and the conjunctival epithelium that surrounds this. These two epithelia are maintained by different stem cell populations (limbal stem cells for the corneal epithelium and the conjunctival epithelial stem cells). In this review, we provide an update on our understanding of these epithelia and their stem cells systems, including embryology, new markers, and controversy around the location of these stem cells. We also provide an update on the translation of this understanding into clinical applications for the treatment of debilitating ocular surface diseases. PMID- 26146506 TI - Anticancer Activity of Saponins from Allium chinense against the B16 Melanoma and 4T1 Breast Carcinoma Cell. AB - The cytotoxic substance of A. chinense saponins (ACSs) was isolated using ethanol extraction and purified with the D101 macroporous adsorption resin approach. We investigated the anticancer activity of ACSs in the B16 melanoma and 4T1 breast carcinoma cell lines. Methylthioninium chloride and hematoxylin-eosin staining with Giemsa dyestuff were used when the cells were treated with ACSs. The results showed that the cells morphologies changed significantly; ACSs induced cell death in B16 and 4T1 cells based on acridine orange/ethidium bromide double fluorescence staining, with the number and degree of apoptotic tumor cells increasing as ACS concentration increased. ACSs inhibited the proliferation of B16 and 4T1 cells in a dose-dependent manner. They also inhibited cell migration and colony formation and exhibited a concentration-dependent effect. In addition, ACSs apparently inhibited the growth of melanoma in vivo. The preliminary antitumor in vivo assay revealed that early medication positively affected tumor inhibition action and effectively protected the liver and spleen of C57 BL/6 mice from injury. This study provides evidence for the cytotoxicity of ACSs and a strong foundation for further research to establish the theoretical basis for cell death and help in the design and development of new anticancer drugs. PMID- 26146507 TI - Hugan Qingzhi Exerts Anti-Inflammatory Effects in a Rat Model of Nonalcoholic Fatty Liver Disease. AB - Ethnopharmacological Relevance. The Hugan Qingzhi tablet (HQT) is a traditional Chinese medicine used for treating NAFLD (nonalcoholic fatty liver disease). The present study evaluated the anti-inflammatory effects of HQT in rats with NAFLD. Materials and Methods. HQT was administered daily to the NAFLD experimental groups. Biochemical markers, histopathological data, and oxidative stress/antioxidant biomarkers were determined. Proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) were detected by enzyme-linked immunoassay. Expressions of silent information regulator 1 (SIRT1) and acetylated-nuclear-factor kappaB-p65 (Ac-NF-kappaB-p65) were performed by western blotting. Results. At high and moderate doses, HQT was highly effective in decreasing serum alanine aminotransferase (P < 0.01), aspartate aminotransferase (P < 0.01), hepatic total cholesterol (P < 0.01), triglycerides (P < 0.01), and free fatty acid levels (P < 0.01). Moreover, high and moderate doses of HQT reduced hepatic levels of the proinflammatory cytokines TNF-alpha (P < 0.01), IL-1beta (P < 0.01), and IL-6 (P < 0.01), enhanced SIRT1 expression, and depressed Ac-NF-kappaB-p65 expression at protein level. Conclusions. In our NAFLD rat model, HQT exerted substantial anti inflammatory and antioxidant activities, possibly involving the regulation of SIRT1 and Ac-NF-kappaB-p65 expression. PMID- 26146509 TI - Migration and Remittances: Evidence from a Poor Province in China. AB - This paper examines patterns of remittances among migrants from Guizhou province of China. Our research is motivated by three lines of theoretical arguments, namely the new economics of migration, a translocal perspective linking remittances and development, and the culture of remittances. Taking individual, household, and village-level characteristics into account, we estimated multilevel logistic models of the decision to remit and multilevel models of the amount of remittances. Our results show that migrant remittance behaviour is responsive to family needs as well as household economic position in the village.. Migrants who come from entrepreneurial households are more likely to remit a large amount than other types of households. We find some evidence of "culture of remittances" in these villages. Consistent with our expectations, migrants who are from villages with higher amount of average remittances are likely to remit a larger amount than otherwise. PMID- 26146508 TI - Positional RNA-Seq identifies candidate genes for phenotypic engineering of sexual traits. AB - INTRODUCTION: RNA interference (RNAi) of trait-specific genes permits the manipulation of specific phenotypic traits ("phenotypic engineering") and thus represents a powerful tool to test trait function in evolutionary studies. The identification of suitable candidate genes, however, often relies on existing functional gene annotation, which is usually limited in emerging model organisms, especially when they are only distantly related to traditional genetic model organisms. A case in point is the free-living flatworm Macrostomum lignano (Lophotrochozoa: Platyhelminthes: Rhabditophora), an increasingly powerful model organism for evolutionary studies of sex in simultaneous hermaphrodites. To overcome the limitation of sparse functional annotation, we have performed a positional RNA-Seq analysis on different body fragments in order to identify organ-specific candidate transcripts. We then performed gene expression (in situ hybridization) and gene function (RNAi) analyses on 23 candidate transcripts, both to evaluate the predictive potential of this approach and to obtain preliminary functional characterizations of these candidate genes. RESULTS: We identified over 4000 transcripts that could be expected to show specific expression in different reproductive organs (including testis, ovary and the male and female genital systems). The predictive potential of the method could then be verified by confirming organ-specific expression for several candidate transcripts, some of which yielded interesting trait-specific knock-down phenotypes that can now be followed up in future phenotypic engineering studies. CONCLUSIONS: Our positional RNA-Seq analysis represents a highly useful resource for the identification of candidate transcripts for functional and phenotypic engineering studies in M. lignano, and it has already been used successfully in several studies. Moreover, this approach can overcome some inherent limitations of homology-based candidate selection and thus should be applicable to a broad range of emerging model organisms. PMID- 26146510 TI - Protocol: genetic transformation of the fern Ceratopteris richardii through microparticle bombardment. AB - BACKGROUND: The inability to genetically transform any fern species has been a major technical barrier to unlocking fern biology. Initial attempts to overcome this limitation were based on transient transformation approaches or achieved very low efficiencies. A highly efficient method of stable transformation was recently reported using the fern Ceratopteris richardii, in which particle bombardment of callus tissue achieved transformation efficiencies of up to 72%. As such, this transformation method represents a highly desirable research tool for groups wishing to undertake fern genetic analysis. RESULTS: We detail an updated and optimized protocol for transformation of C. richardii by particle bombardment, including all necessary ancillary protocols for successful growth and propagation of this species in a laboratory environment. The C. richardii lifecycle comprises separate, free-living gametophyte and sporophyte stages. Callus is induced from the sporophyte apex through growth on cytokinin-containing tissue culture medium and can be maintained indefinitely by sub-culturing. Transgene DNA is introduced into callus cells through particle bombardment, and stable genomic integration events are selected by regeneration and growth of T0 sporophytes for a period of 8 weeks on medium containing antibiotics. Selection of T1 transgenic progeny is accomplished through screening T1 gametophytes for antibiotic resistance. In many cases sexual reproduction and development of transgenic embryos requires growth and fertilization of gametophytes in the absence of antibiotics, followed by a separate screen for antibiotic resistance in the resultant sporophyte generation. CONCLUSIONS: Genetic transformation of C. richardii using this protocol was found to be robust under a broad range of bombardment and recovery conditions. The successful expansion of the selection toolkit to include a second antibiotic for resistance screening (G-418) and different resistance marker promoters increases the scope of transformations possible using this technique and offers the prospect of more complex analysis, for example the creation of lines carrying more than one transgene. The introduction of a robust and practicable transformation technique is a very important milestone in the field of fern biology, and its successful implementation in C. richardii paves the way for adoption of this species as the first fern genetic model. PMID- 26146511 TI - Scientific Challenges to Free Will and Moral Responsibility. AB - Here, I review work from three lines of research in cognitive science often taken to threaten free will and moral responsibility. This work concerns conscious deciding, the experience of acting, and the role of largely unnoticed situational influences on behavior. Whether this work in fact threatens free will and moral responsibility depends on how we ought to interpret it, and depends as well on the nature of free and responsible behavior. I discuss different ways this work has been interpreted and argue that though work on conscious deciding and the experience of acting presents no real threat, work on situational influences is more difficult to dismiss. This work may present a real threat, and it may require us to revise our commonsense understanding of free and responsible behavior. But this work may also present ways to augment free and responsible behavior. Determining whether and how advancing science threatens, enhances, or simply describes free will is an ongoing task for scientists and philosophers alike. PMID- 26146512 TI - Medical Image Fusion Based on Rolling Guidance Filter and Spiking Cortical Model. AB - Medical image fusion plays an important role in diagnosis and treatment of diseases such as image-guided radiotherapy and surgery. Although numerous medical image fusion methods have been proposed, most of these approaches are sensitive to the noise and usually lead to fusion image distortion, and image information loss. Furthermore, they lack universality when dealing with different kinds of medical images. In this paper, we propose a new medical image fusion to overcome the aforementioned issues of the existing methods. It is achieved by combining with rolling guidance filter (RGF) and spiking cortical model (SCM). Firstly, saliency of medical images can be captured by RGF. Secondly, a self-adaptive threshold of SCM is gained by utilizing the mean and variance of the source images. Finally, fused image can be gotten by SCM motivated by RGF coefficients. Experimental results show that the proposed method is superior to other current popular ones in both subjectively visual performance and objective criteria. PMID- 26146513 TI - Enhancing the Lasso Approach for Developing a Survival Prediction Model Based on Gene Expression Data. AB - In the past decade, researchers in oncology have sought to develop survival prediction models using gene expression data. The least absolute shrinkage and selection operator (lasso) has been widely used to select genes that truly correlated with a patient's survival. The lasso selects genes for prediction by shrinking a large number of coefficients of the candidate genes towards zero based on a tuning parameter that is often determined by a cross-validation (CV). However, this method can pass over (or fail to identify) true positive genes (i.e., it identifies false negatives) in certain instances, because the lasso tends to favor the development of a simple prediction model. Here, we attempt to monitor the identification of false negatives by developing a method for estimating the number of true positive (TP) genes for a series of values of a tuning parameter that assumes a mixture distribution for the lasso estimates. Using our developed method, we performed a simulation study to examine its precision in estimating the number of TP genes. Additionally, we applied our method to a real gene expression dataset and found that it was able to identify genes correlated with survival that a CV method was unable to detect. PMID- 26146514 TI - Revisiting Warfarin Dosing Using Machine Learning Techniques. AB - Determining the appropriate dosage of warfarin is an important yet challenging task. Several prediction models have been proposed to estimate a therapeutic dose for patients. The models are either clinical models which contain clinical and demographic variables or pharmacogenetic models which additionally contain the genetic variables. In this paper, a new methodology for warfarin dosing is proposed. The patients are initially classified into two classes. The first class contains patients who require doses of >30 mg/wk and the second class contains patients who require doses of <=30 mg/wk. This phase is performed using relevance vector machines. In the second phase, the optimal dose for each patient is predicted by two clinical regression models that are customized for each class of patients. The prediction accuracy of the model was 11.6 in terms of root mean squared error (RMSE) and 8.4 in terms of mean absolute error (MAE). This was 15% and 5% lower than IWPC and Gage models (which are the most widely used models in practice), respectively, in terms of RMSE. In addition, the proposed model was compared with fixed-dose approach of 35 mg/wk, and the model proposed by Sharabiani et al. and its outperformance were proved in terms of both MAE and RMSE. PMID- 26146515 TI - The Technological Growth in eHealth Services. AB - The infusion of information communication technology (ICT) into health services is emerging as an active area of research. It has several advantages but perhaps the most important one is providing medical benefits to one and all irrespective of geographic boundaries in a cost effective manner, providing global expertise and holistic services, in a time bound manner. This paper provides a systematic review of technological growth in eHealth services. The present study reviews and analyzes the role of four important technologies, namely, satellite, internet, mobile, and cloud for providing health services. PMID- 26146516 TI - Chromosome territory repositioning induced by PHA-activation of lymphocytes: A 2D and 3D appraisal. AB - BACKGROUND: Genomes and by extension chromosome territories (CTs) in a variety of organisms exhibit nonrandom organization within interphase nuclei. CTs are susceptible to movement upon induction by a variety of stimuli, including: cell differentiation, growth factors, genotoxic agents, proliferating status, and stimulants that induce novel transcription profiles. These findings suggest nuclear architecture can undergo reorganization, providing support for a functional significance of CT organization. The effect of the initiation of transcription on global scale chromatin architecture has been underexplored. This study investigates the organization of all 24 human chromosomes in lymphocytes from two individuals in resting and phytohaemagglutinin activated lymphocytes using 2D and 3D approaches. RESULTS: The radial organization of CTs in lymphocytes in both resting and activated lymphocytes follows a gene-density pattern. However, CT organization in activated nuclei appears less constrained exhibiting a more random organization. We report differences in the spatial relationship between homologous and heterologous CTs in activated nuclei. In addition, a reproducible radial hierarchy of CTs was identified and evidence of a CT repositioning was observed in activated nuclei using both 2D and 3D approaches. CONCLUSIONS: Alterations between resting and activated lymphocytes could be adaptation of CTs to the new transcription profile and possibly the formation of new neighborhoods of interest or interaction of CTs with nuclear landmarks. The increased distances between homologous and heterologous CTs in activated lymphocytes could be a reflection of a defensive mechanism to reduce potential interaction to prevent any structural chromosome abnormalities (e.g. translocations) as a result of DNA damage that increases during lymphocyte activation. PMID- 26146518 TI - Insertion of a pressure sensing arrayminimally affects hindfoot bone kinematics. AB - BACKGROUND: Understanding the development of ankle osteoarthritis (OA) is of high importance and interest; however its causality is poorly understood and several links to joint loading conditions have been made. One way of quantifying joint loading conditions is by measuring the intra-articular pressure distribution during gait simulations performed by in-vitro experimental set-ups. However the effect of inserting a pressure sensing array in the ankle joint could potentially disturb the proper kinematics and therefore the loading conditions. METHODS: In this study, we performed in-vitro gait simulations in 7 cadaveric feet, before and after inserting a pressure sensing array and quantified the effect on the joints range of motion (ROM). The gait was simulated with a stance phase duration of one second using a custom build cadaveric gait simulator (CGS). RESULTS: The results show a limited effect in the ROM for all the joints of the hind foot, not exceeding the variability observed in specimens without a sensor. However, no consistent direction (increase/decrease) can be observed. CONCLUSION: The results suggest that even though the effect of inserting a pressure sensing array is minimal, it needs to be evaluated against the demands/requirements of the application. PMID- 26146519 TI - Analysis of the talocrural and subtalar joint motions in patients with medial tibial stress syndrome. AB - BACKGROUND: The rearfoot motion during sports activities in patients with the medial tibial stress syndrome (MTSS) is unknown. This study aimed to investigate the difference in kinematics of the rearfoot in MTSS patients (eight male soccer players) and control participants (eight male soccer players) during a forward step. METHODS: Sixteen male soccer players, including eight players with MTSS, participated. Forward step trials were recorded with cineradiographic images obtained at a sampling rate of 60 Hz. Geometric bone models of the tibia and talus/calcaneus were created from computed tomography scans of the distal part of one lower limb. Following a combination of approaches, anatomical coordinate systems were embedded in each bone model. The talocrural joint motion (relative motion of the talus with respect to the tibia) and subtalar joint motion (relative motion of the calcaneus with respect to the talus) were examined. RESULTS: A significantly larger range of internal/external rotation and inversion/eversion motion was observed in the subtalar joint of MTSS patients compared to healthy controls (P < 0.05) from heel contact to heel off. There were no significant differences between the MTSS patients and healthy participants in the ranges of all talocrural joint angles during the forward step. CONCLUSION: Our results indicate that the range of subtalar joint motion is greater in patients with MTSS during the stance phase of the forward step. The kinematic results obtained of this study may have important clinical implications and add quantitative data to an in vivo database of MTSS patients. PMID- 26146520 TI - Joint space width of the tibiotalar joint in the healthy foot. AB - BACKGROUND: It is important to evaluate dynamic changes in the joint space width of the ankle mortise in detail in order to better understand the pathology of foot and ankle disorders. However, there are few reports on changes in the joint space width of the foot and ankle assessed using 3D images. The purpose of this study was to determine the changes in the joint space width of the ankle (tibiotalar joint) in association with dorsiflexion and plantar flexion of the ankle joint in healthy feet. METHODS: Computed tomography (CT) images of 10 healthy feet were obtained in the neutral, plantarflexed and dorsiflexed positions of the ankle joint, from which 3D virtual models were fabricated of the tibia, fibula and talus. The 3D joint space width in these models was calculated using a custom made software program. RESULTS: The joint space width increased in the order of dorsiflexion, neutral position and plantar flexion. Regarding the amount of change in dorsiflexion and plantar flexion relative to the neutral position, there were no significant differences in the middle-middle position. On the other hand, there were highly significant differences in the medial-anterior, medial-middle and medial-posterior positions. CONCLUSIONS: The joint space width of the ankle joint can be calculated accurately using 3D reconstruction images. Our findings should assist in clarifying pathology associated with movement of the ankle during the gait cycle based on changes in the joint space width in feet exhibiting disorders. PMID- 26146521 TI - Let me Google that for you: a time series analysis of seasonality in internet search trends for terms related to foot and ankle pain. AB - BACKGROUND: The analysis of internet search traffic may present the opportunity to gain insights into general trends and patterns in information seeking behaviour related to medical conditions at a population level. For prevalent and widespread problems such as foot and ankle pain, this information has the potential to improve our understanding of seasonality and trends within these conditions and their treatments, and may act as a useful proxy for their true incidence/prevalence characteristics. This study aimed to explore seasonal effects, general trends and relative popularity of internet search terms related to foot and ankle pain over the past decade. METHODS: We used the Google Trends tool to obtain relative search engine traffic for terms relating to foot and ankle pain and common treatments from Google search and affiliated pages for major northern and southern hemisphere English speaking nations. Analysis of overall trends and seasonality including summer/winter differences was carried out on these terms. RESULTS: Searches relating to general foot pain were on average 3.4 times more common than those relating to ankle pain, and twice as common as searches relating to heel pain. Distinct seasonal effects were seen in the northern hemisphere, with large increases in search volumes in the summer months compared to winter for foot (p = 0.004, 95 % CI [22.2-32.1]), ankle (p = 0.0078, 95 % CI [20.9-35.5]), and heel pain (p = 0.004, 95 % CI [29.1-45.6]). These seasonal effects were reflected by data from Australia, with the exception of ankle pain. Annual seasonal effects for treatment options were limited to terms related to foot surgery and ankle orthoses (p = 0.031, 95 % CI [3.5-20.9]; p = 0.004, 95 % CI [7.6-25.2] respectively), again increasing in the summer months. CONCLUSIONS: A number of general trends and annual seasonal effects were found in time series internet search data for terms relating to foot and ankle pain. This data may provide insights into these conditions at population levels. PMID- 26146522 TI - Predictors of all-cause and cardiovascular disease mortality in type 2 diabetes: Diabetes Heart Study. AB - BACKGROUND: Many studies evaluated the best predictors for cardiovascular disease (CVD) events in individuals with type 2 diabetes (T2D), but few studies examined the factors most strongly associated with mortality in T2D. The Diabetes Heart Study (DHS), an intensively phenotyped family-based cohort enriched for T2D, provided an opportunity to address this question. METHODS: Associations with mortality were examined in 1022 European Americans affected by T2D from 476 DHS families. All-cause mortality was 31.2 % over an average 9.6 years of follow-up. Cox proportional hazards models with sandwich-based variance estimation were used to evaluate associations between all-cause and CVD mortality and 24 demographic and clinical factors, including coronary artery calcified plaque (CAC), carotid artery intima-media thickness, medications, body mass index, waist hip ratio, lipids, blood pressure, kidney function, QT interval, educational attainment, and glycemic control. Nominally significant factors (p < 0.25) from univariate analyses were included in model selection (backward elimination, forward selection, and stepwise selection). Age and sex were included in all models. RESULTS: The all-cause mortality model selected from the full DHS sample included age, sex, CAC, urine albumin: creatinine ratio (UACR), insulin use, current smoking, and educational attainment. The CVD mortality model selected from the full sample included age, sex, CAC, UACR, triglycerides, and history of CVD events. Beyond age, the most significant associations for both mortality models were CAC (2.03 * 10(-4) <= p <= 0.001) and UACR (1.99 * 10(-8) <= p <= 2.23 * 10( 8)). To confirm the validity of the main predictors identified with model selection using the full sample, a two-fold cross-validation approach was used, and similar results were observed. CONCLUSIONS: This analysis highlights important demographic and clinical factors, notably CAC and albuminuria, which predict mortality in the general population of patients with T2D. PMID- 26146517 TI - Iodine intake as a risk factor for thyroid cancer: a comprehensive review of animal and human studies. AB - Thyroid cancer (TC) is the most common endocrine malignancy and in most countries, incidence rates are increasing. Although differences in population iodine intake are a determinant of benign thyroid disorders, the role of iodine intake in TC remains uncertain. We review the evidence linking iodine intake and TC from animal studies, ecological studies of iodine intake and differentiated and undifferentiated TC, iodine intake and mortality from TC and occult TC at autopsy, as well as the case-control and cohort studies of TC and intake of seafood and milk products. We perform a new meta-analysis of pooled measures of effect from case-control studies of total iodine intake and TC. Finally, we examine the post-Chernobyl studies linking iodine status and risk of TC after radiation exposure. The available evidence suggests iodine deficiency is a risk factor for TC, particularly for follicular TC and possibly, for anaplastic TC. This conclusion is based on: a) consistent data showing an increase in TC (mainly follicular) in iodine deficient animals; b) a plausible mechanism (chronic TSH stimulation induced by iodine deficiency); c) consistent data from before and after studies of iodine prophylaxis showing a decrease in follicular TC and anaplastic TC; d) the indirect association between changes in iodine intake and TC mortality in the decade from 2000 to 2010; e) the autopsy studies of occult TC showing higher microcarcinoma rates with lower iodine intakes; and f) the case control studies suggesting lower risk of TC with higher total iodine intakes. PMID- 26146523 TI - What is the most appropriate lipid profile ratio predictor for insulin resistance in each sex? A cross-sectional study in Korean populations (The Fifth Korea National Health and Nutrition Examination Survey). AB - BACKGROUND: Insulin resistance (IR) reduces reactivity of the target organ to blood insulin. Researchers have attempted to evaluate IR using various serum lipid concentration ratios. We aimed to determine the most strongly IR-predictive lipid profile ratios for each sex by studying associations between lipid concentration ratios and IR using data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1) 2010. METHODS: Overall, 8958 individuals participated in health interview and examination surveys. Among them, 1910 individuals who completed physical examinations and 8-h fasting blood tests and were older than 20 years of age were enrolled (929 men and 981 women). The lipid-ratio-related study outcomes were the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), triglyceride (TG)/HDL-C, and non-HDL-C (LDL-C + TG/5)/HDL-C ratios. We divided subjects into 4 groups according to lipid profile ratio quartiles for a comparison of homeostasis model assessment (HOMA)-IR values. Regression analyses were performed after adjusting for the confounding factors of age, body mass index, and diabetes mellitus history. RESULTS: HOMA-IR values tended to increase significantly along with LDL-C/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios in both sexes. In men, multiple linear regression analyses showed that after adjusting for confounding factors, a significant positive association remained only with the LDL-C/HDL-C ratio (p = 0.0238, R(2) = 0.3605, root mean squared error [MSE] =0.3512). In women, multiple linear regression analyses showed that after adjusting for confounding factors, significant positive associations remained with the LDL C/HDL-C (p < 0.0001, R-square = 0.2329, root MSE = 0.3776), TG/HDL-C (p = 0.0001, R(2) = 0.2373, root MSE = 0.3766), and non-HDL-C/HDL-C ratios (p < 0.0001, R(2) = 0.2456, root MSE = 0.3745). CONCLUSION: The LDL-C/HDL-C ratio in men and LDL C/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios in women might be clinically significant predictors of IR in healthy Korean adults. However, additional large scale studies are required to confirm these findings. PMID- 26146524 TI - New developments in the pathology of malignant lymphoma: a review of literature published from January 2015 to April 2015. PMID- 26146525 TI - Phonetic reduction and variation in American Sign Language: A quantitative study of sign lowering. AB - During normal sign language use, a signer's productions will often be reduced from the citation forms of signs. This study examines a form of phonetic reduction in American Sign Language, in which signs that are located at the forehead are lowered in space. In particular, we explore the effects of signing rate and phonetic environment on the lowering of specific ASL signs and on their phonetic variation along the other two movement axes. Movement data were captured as native signers produced utterances that were controlled for phonetic environment and signing rate. We found that all signers produced lowered forms as an effect of the phonetic factors that we manipulated. In addition, several rate induced effects occurred, which we had not predicted. Results are discussed in relation to past research on variation in sign production and in speech. PMID- 26146526 TI - Measuring health care costs of individuals with employer-sponsored health insurance in the U.S.: A comparison of survey and claims data. AB - As the core nationally representative health expenditure survey in the United States, the Medical Expenditure Panel Survey (MEPS) is increasingly being used by statistical agencies to track expenditures by disease. However, while MEPS provides a wealth of data, its small sample size precludes examination of spending on all but the most prevalent health conditions. To overcome this issue, statistical agencies have turned to other public data sources, such as Medicare and Medicaid claims data, when available. No comparable publicly available data exist for those with employer-sponsored insurance. While large proprietary claims databases may be an option, the relative accuracy of their spending estimates is not known. This study compared MEPS and MarketScan estimates of annual per person health care spending on individuals with employer-sponsored insurance coverage. Both total spending and the distribution of annual per person spending differed across the two data sources, with MEPS estimates 10 percent lower on average than estimates from MarketScan. These differences appeared to be a function of both underrepresentation of high expenditure cases and underestimation across the remaining distribution of spending. PMID- 26146527 TI - The Role of Cardiac MRI in Patients with Troponin-Positive Chest Pain and Unobstructed Coronary Arteries. AB - Acute coronary syndrome (ACS) still remains one of the leading causes of mortality and morbidity worldwide. Seven to fifteen percent of patients presenting with ACS have unobstructed coronary artery disease (CAD) on urgent angiography. Patients with ACS and unobstructed coronary arteries represent a clinical dilemma and their diagnosis and management is quite variable in current practice. Cardiovascular magnetic resonance imaging with its unique non-invasive myocardial tissue characterization property has the potential to identify underlying etiologies and reach a final diagnosis. These include acute and chronic myocarditis, embolic/spontaneous recanalization myocardial infarction, and Tako-Tsubo cardiomyopathy, and other conditions. Establishing a final diagnosis has a direct implication on patient's management and prognosis. In this article, we have reviewed the current evidence on the diagnostic role of cardiac magnetic resonance (CMR) in patients with ACS and unobstructed coronary arteries. We have also highlighted the potential role of CMR as a risk stratification or prognostication tool for this patient population. PMID- 26146528 TI - Transplanted Neural Stem Cells: Playing a Neuroprotective Role by Ceruloplasmin in the Substantia Nigra of PD Model Rats? AB - Although mounting evidence suggests that ceruloplasmin (CP) deficiency and iron deposition are pivotal factors responsible for exacerbating demise of dopaminergic neurons in the substantia nigra (SN) of the Parkinsonism and neural stem cells (NSCs) are believed to be excellent candidates for compensating the lost dopaminergic neurons, there are few researches to explore the change of CP expression and of iron deposition in the pathological microenvironment of SN after NSCs transplantation and the ability of grafted NSCs to differentiate directionally into dopaminergic neurons under the changed homeostasis. With substantia nigral stereotaxic technique and NSCs transplantation, we found that tyrosine hydroxylase and CP expression decreased and iron deposition increased in the lesioned SN after 6-OHDA administration compared with control, while tyrosine hydroxylase and CP expression increased and iron deposition decreased after NSCs transplantation compared to 6-OHDA administration alone. Only a small number of embedding NSCs are able to differentiate into dopaminergic neurons. These results suggest that grafted NSCs have an influence on improving the content of CP expression, which may play a neuroprotective role by decreasing iron deposition and ameliorating damage of dopaminergic neurons and possibly underline the iron related common mechanism of Parkinson's disease and Wilson's disease. PMID- 26146530 TI - Immigration and Prosecutorial Discretion. AB - Immigration has become an increasingly salient national issue in the US, and the Department of Justice recently increased federal efforts to prosecute immigration offenses. This shift, however, relies on the cooperation of US attorneys and their assistants. Traditionally federal prosecutors have enjoyed enormous discretion and have been responsive to local concerns. To consider how the centralized goal of immigration enforcement may have influenced federal prosecutors in regional offices, we review their prosecution of immigration offenses in California using over a decade's worth of data. Our findings suggest that although centralizing forces influence immigration prosecutions, individual US attorneys' offices retain distinct characteristics. Local factors influence federal prosecutors' behavior in different ways depending on the office. Contrary to expectations, unemployment rates did not affect prosecutors' willingness to pursue immigration offenses, nor did local popular opinion about illegal immigration. PMID- 26146531 TI - Template Registration with Missing Parts: Application to the Segmentation of M. Tuberculosis Infected Lungs. AB - Many techniques have been proposed to segment organs from images, however the segmentation of diseased organs remains challenging and frequently requires lots of user interaction. The challenge consists of segmenting an organ while its appearance and its shape vary due to the presence of the disease in addition to individual variations. We propose a template registration technique that can be used to recover the complete segmentation of a diseased organ from a partial segmentation. The usual template registration method is modified in such a way that it is robust to missing parts. The proposed method is used to segment Mycobacterium tuberculosis infected lungs in CT images of experimentally infected mice. Using synthetic data, we evaluate and compare the performance of the proposed algorithm with the usual sum of squared difference cost function. PMID- 26146529 TI - Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story. AB - Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models. PMID- 26146532 TI - Incorporating User Input in Template-Based Segmentation. AB - We present a simple and elegant method to incorporate user input in a template based segmentation method for diseased organs. The user provides a partial segmentation of the organ of interest, which is used to guide the template towards its target. The user also highlights some elements of the background that should be excluded from the final segmentation. We derive by likelihood maximization a registration algorithm from a simple statistical image model in which the user labels are modeled as Bernoulli random variables. The resulting registration algorithm minimizes the sum of square differences between the binary template and the user labels, while preventing the template from shrinking, and penalizing for the inclusion of background elements into the final segmentation. We assess the performance of the proposed algorithm on synthetic images in which the amount of user annotation is controlled. We demonstrate our algorithm on the segmentation of the lungs of Mycobacterium tuberculosis infected mice from MUCT images. PMID- 26146533 TI - Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders. AB - BACKGROUND: Autism spectrum disorders (ASDs) likely involve dysregulation of multiple genes related to brain function and development. Abnormalities in individual regulatory small non-coding RNA (sncRNA), including microRNA (miRNA), could have profound effects upon multiple functional pathways. We assessed whether a brain region associated with core social impairments in ASD, the superior temporal sulcus (STS), would evidence greater transcriptional dysregulation of sncRNA than adjacent, yet functionally distinct, primary auditory cortex (PAC). METHODS: We measured sncRNA expression levels in 34 samples of postmortem brain from STS and PAC to find differentially expressed sncRNA in ASD compared with control cases. For differentially expressed miRNA, we further analyzed their predicted mRNA targets and carried out functional over representation analysis of KEGG pathways to examine their functional significance and to compare our findings to reported alterations in ASD gene expression. RESULTS: Two mature miRNAs (miR-4753-5p and miR-1) were differentially expressed in ASD relative to control in STS and four (miR-664-3p, miR-4709-3p, miR-4742-3p, and miR-297) in PAC. In both regions, miRNA were functionally related to various nervous system, cell cycle, and canonical signaling pathways, including PI3K-Akt signaling, previously implicated in ASD. Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain. CONCLUSIONS: Alterations in sncRNA may underlie dysregulation of molecular pathways implicated in autism. sncRNA transcriptional abnormalities in ASD were apparent in STS and in PAC, a brain region not directly associated with core behavioral impairments. Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS. PMID- 26146534 TI - Sex differences in cortical volume and gyrification in autism. AB - BACKGROUND: Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate sample sizes are critical for improving our understanding of the biological mechanisms underlying ASD in females. METHODS: We leveraged the open-access autism brain imaging data exchange (ABIDE) dataset to obtain structural brain imaging data from 53 females with ASD, who were matched with equivalent samples of males with ASD, and their typically developing (TD) male and female peers. Brain images were processed with FreeSurfer to assess three key features of local cortical morphometry: volume, thickness, and gyrification. A whole-brain approach was used to identify significant effects of sex, diagnosis, and sex-by-diagnosis interaction, using a stringent threshold of p < 0.01 to control for false positives. Stability and power analyses were conducted to guide future research on sex differences in ASD. RESULTS: We detected a main effect of sex in the bilateral superior temporal cortex, driven by greater cortical volume in females compared to males in both the ASD and TD groups. Sex-by-diagnosis interaction was detected in the gyrification of the ventromedial/orbitofrontal prefrontal cortex (vmPFC/OFC). Post-hoc analyses revealed that sex-by-diagnosis interaction was driven by reduced vmPFC/OFC gyrification in males with ASD, compared to females with ASD as well as TD males and females. Finally, stability analyses demonstrated a dramatic drop in the likelihood of observing significant clusters as the sample size decreased, suggesting that previous studies have been largely underpowered. For instance, with a sample of 30 females with ASD (total n = 120), a significant sex-by-diagnosis interaction was only detected in 50 % of the simulated subsamples. CONCLUSIONS: Our results demonstrate that some features of typical sex differences are preserved in the brain of individuals with ASD, while others are not. Sex differences in ASD are associated with cortical regions involved in language and social function, two domains of deficits in the disorder. Stability analyses provide novel quantitative insights into why smaller samples may have previously failed to detect sex differences. PMID- 26146535 TI - Thiosquaramides: pH switchable anion transporters. AB - The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquaramides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH. PMID- 26146536 TI - Bioorthogonal Oxime Ligation Mediated In Vivo Cancer Targeting. AB - Current cancer targeting relying on specific biological interaction between cell surface antigen and respective antibody or its analogue has proven to be effective in the treatment of different cancers; however, this strategy has its own limitations, such as heterogeneity of cancer cells and immunogenicity of the biomacromolecule binding ligands. Bioorthogonal chemical conjugation has emerged as an attractive alternative to biological interaction for in vivo cancer targeting. Here, we report an in vivo cancer targeting strategy mediated by bioorthogonal oxime ligation. Oxyamine group, the artificial target, is introduced onto 4T1 murine breast cancer cells through liposome delivery and fusion. Poly(ethylene glycol) -polylactide (PEG-PLA) nanoparticle (NP) is surface functionalized with aldehyde groups as targeting ligands. The improved in vivo cancer targeting of PEG-PLA NPs is achieved through specific and efficient chemical reaction between the oxyamine and aldehyde groups. PMID- 26146537 TI - Pattern-Based Detection of Anion Pollutants in Water with DNA Polyfluorophores. AB - Many existing irrigation, industrial and chemical storage sites are currently introducing hazardous anions into groundwater, making the monitoring of such sites a high priority. Detecting and quantifying anions in water samples typically requires complex instrumentation, adding cost and delaying analysis. Here we address these challenges by development of an optical molecular method to detect and discriminate a broad range of anionic contaminants with DNA-based fluorescent sensors. A library of 1296 tetrameric-length oligodeoxyfluorosides (ODFs) composed of metal ligand and fluorescence modulating monomers was constructed with a DNA synthesizer on PEG-polystyrene microbeads. These oligomers on beads were incubated with YIII or ZnII ions to provide affinity and responsiveness to anions. Seventeen anions were screened with the library under an epifluorescence microscope, ultimately yielding eight chemosensors that could discriminate 250 MUM solutions of all 17 anions in buffered water using their patterns of response. This sensor set was able to identify two unknown anion samples from ten closely-responding anions and could also function quantitatively, determining unknown concentrations of anions such as cyanide (as low as 1 mM) and selenate (as low as 50 MUM). Further studies with calibration curves established detection limits of selected anions including thiocyanate (detection limit ~300 MUM) and arsenate (~800 MUM). The results demonstrate DNA like fluorescent chemosensors as versatile tools for optically analyzing environmentally hazardous anions in aqueous environments. PMID- 26146538 TI - Tuning the Reactivity of Mononuclear Nonheme Manganese(IV)-Oxo Complexes by Triflic Acid. AB - Triflic acid (HOTf)-bound nonheme Mn(IV)-oxo complexes, [(L)MnIV(O)]2+-(HOTf)2 (L = N4Py and Bn-TPEN; N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) and Bn-TPEN = N-benzyl-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine), were synthesized by adding HOTf to the solutions of the [(L)MnIV(O)]2+ complexes and were characterized by various spectroscopies. The one-electron reduction potentials of the MnIV(O) complexes exhibited a significant positive shift upon binding of HOTf. The driving force dependence of electron transfer (ET) from electron donors to the MnIV(O) and MnIV(O)-(HOTf)2 complexes were examined and evaluated in light of the Marcus theory of ET to determine the reorganization energies of ET. The smaller reorganization energies and much more positive reduction potentials of the [(L)MnIV(O)]2+-(HOTf)2 complexes resulted in much enhanced oxidation capacity towards one-electron reductants and para-X substituted-thioanisoles. The reactivities of the Mn(IV)-oxo complexes were markedly enhanced by binding of HOTf, such as a 6.4 * 105-fold increase in the oxygen atom transfer (OAT) reaction (i.e., sulfoxidation). Such a remarkable acceleration in the OAT reaction results from the enhancement of ET from para-X substituted-thioanisoles to the MnIV(O) complexes as revealed by the unified ET driving force dependence of the rate constants of OAT and ET reactions of [(L)MnIV(O)]2+-(HOTf)2. In contrast, deceleration was observed in the rate of H atom transfer (HAT) reaction of [(L)MnIV(O)]2+-(HOTf)2 complexes with 1,4 cyclohexadiene as compared with those of the [(L)MnIV(O)]2+ complexes. Thus, the binding of two HOTf molecules to the MnIV(O) moiety resulted in remarkable acceleration of the ET rate when the ET is thermodynamically feasible. When the ET reaction is highly endergonic, the rate of the HAT reaction is decelerated due to the steric effect of the counter anion of HOTf. PMID- 26146540 TI - Novel oral taxane therapies: recent Phase I results. AB - The oral taxanes are analogues of existing taxanes with a possible broad range of antitumor activity. They also have the potential advantages of ease of administration, better efficacy and lesser toxicity than currently available taxanes. These drugs have been used in several Phase I clinical trials, the methodology and results of which will be reviewed here. PMID- 26146539 TI - Outcome measures for clinical trials assessing treatment of cystic fibrosis lung disease. AB - Cystic fibrosis (CF) is a complex genetic disease characterized by death from loss of lung function. Therapies target pathophysiologic changes associated with pulmonary disease progression. Although therapeutic mechanisms differ, efficacy demonstration is limited to a few accepted outcome measures, each with shortcomings that are becoming more pronounced as CF population health improves. Pulmonary function improvement (as forced expiratory volume in 1 s [FEV1]) and reduction of pulmonary exacerbation risk are commonly used outcomes. Changes in FEV1 decline rate, quality of life, linear growth and/or weight gain are less utilized outcomes. Validated outcomes tend to work best in subjects with more aggressive or advanced lung disease and less so in healthier subjects. Assays of effects on primary therapeutic targets have yet to be validated as surrogate measures of clinical efficacy. As CF population health improves, it will become increasingly difficult to employ current clinical outcome measures to demonstrate efficacy. PMID- 26146541 TI - Background, Structure and Priorities of the 2013 Geneva Declaration on Person centered Health Research. AB - Declarations are relevant tools to frame new areas in health care, to raise awareness and to facilitate knowledge-to-action. The International College on Person Centered Medicine (ICPCM) is seeking to extend the impact of the ICPCM Conference Series by producing a declaration on every main topic. The aim of this paper is to describe the development of the 2013 Geneva Declaration on Person centered Health Research and to provide additional information on the research priority areas identified during this iterative process. There is a need for more PCM research and for the incorporation of the PCM approach into general health research. Main areas of research focus include: Conceptual, terminological, and ontological issues; research to enhance the empirical evidence of PCM main components such as PCM informed clinical communication; PCM-based diagnostic models; person-centered care and interventions; and people-centered care, research on training and curriculum development. Dissemination and implementation of PCM knowledge-base is integral to Person-centered Health Research and shall engage currently available scientific and translational dissemination tools such journals, events and eHealth. PMID- 26146542 TI - Akt-mediated phosphorylation controls the activity of the Y-box protein MSY3 in skeletal muscle. AB - BACKGROUND: The Y-box protein MSY3/Csda represses myogenin transcription in skeletal muscle by binding a highly conserved cis-acting DNA element located just upstream of the myogenin minimal promoter (myogHCE). It is not known how this MSY3 activity is controlled in skeletal muscle. In this study, we provide multiple lines of evidence showing that the post-translational phosphorylation of MSY3 by Akt kinase modulates the MSY3 repression of myogenin. METHODS: Skeletal muscle and myogenic C2C12 cells were used to study the effects of MSY3 phosphorylation in vivo and in vitro on its sub-cellular localization and activity, by blocking the IGF1/PI3K/Akt pathway, by Akt depletion and over expression, and by mutating potential MSY3 phosphorylation sites. RESULTS: We observed that, as skeletal muscle progressed from perinatal to postnatal and adult developmental stages, MSY3 protein became gradually dephosphorylated and accumulated in the nucleus. This correlated well with the reduction of phosphorylated active Akt. In C2C12 myogenic cells, blocking the IGF1/PI3K/Akt pathway using LY294002 inhibitor reduced MSY3 phosphorylation levels resulting in its accumulation in the nuclei. Knocking down Akt expression increased the amount of dephosphorylated MSY3 and reduced myogenin expression and muscle differentiation. MSY3 phosphorylation by Akt in vitro impaired its binding at the MyogHCE element, while blocking Akt increased MSY3 binding activity. While Akt over-expression rescued myogenin expression in MSY3 overexpressing myogenic cells, ablation of the Akt substrate, (Ser126 located in the MSY3 cold shock domain) promoted MSY3 accumulation in the nucleus and abolished this rescue. Furthermore, forced expression of Akt in adult skeletal muscle induced MSY3 phosphorylation and myogenin derepression. CONCLUSIONS: These results support the hypothesis that MSY3 phosphorylation by Akt interferes with MSY3 repression of myogenin circuit activity during muscle development. This study highlights a previously undescribed Akt-mediated signaling pathway involved in the repression of myogenin expression in myogenic cells and in mature muscle. Given the significance of myogenin regulation in adult muscle, the Akt/MSY3/myogenin regulatory circuit is a potential therapeutic target to counteract muscle degenerative disease. PMID- 26146543 TI - The roles of microRNAs in the regulation of tumor metastasis. AB - MicroRNAs (miRNAs) are small noncoding regulatory RNAs that regulate gene expression post-transcriptionally by either inhibiting protein translation or degrading target mRNAs. The differential expression profiles of miRNAs in different types of cancers and in the multi-step process of tumor progression indicate that miRNAs are involved in tumor onset, growth and progression. Metastasis is the most common cause of cancer-related mortality. Current evidence demonstrates that aberrant miRNA expression promotes or inhibits tumor metastasis by modulating the expression of numerous target genes. Therefore, the identification of metastasis-related miRNAs and a better understanding of the complex functions of miRNAs in tumor metastasis will provide potential diagnostic and prognostic biomarkers, as well as therapeutic targets for clinical application. Here, we review the functions of miRNAs in the control of multiple steps of tumor metastasis. PMID- 26146544 TI - Hypoxia induces calpain activity and degrades SMAD2 to attenuate TGFbeta signaling in macrophages. AB - BACKGROUND: Under inflammatory conditions or during tumor progression macrophages acquire distinct phenotypes, with factors of the microenvironment such as hypoxia and transforming growth factor beta (TGFbeta) shaping their functional plasticity. TGFbeta is among the factors causing alternative macrophage activation, which contributes to tissue regeneration and thus, resolution of inflammation but may also provoke tumor progression. However, the signal crosstalk between TGFbeta and hypoxia is ill defined. RESULTS: Exposing human primary macrophages to TGFbeta elicited a rapid SMAD2/SMAD3 phosphorylation. This early TGFbeta-signaling remained unaffected by hypoxia. However, with prolonged exposure periods to TGFbeta/hypoxia the expression of SMAD2 declined because of decreased protein stability. In parallel, hypoxia increased mRNA and protein amount of the calpain regulatory subunit, with the further notion that TGFbeta/hypoxia elicited calpain activation. The dual specific proteasome/calpain inhibitor MG132 and the specific calpain inhibitor 1 rescued SMAD2 degradation, substantiating the ability of calpain to degrade SMAD2. Decreased SMAD2 expression reduced TGFbeta transcriptional activity of its target genes thrombospondin 1, dystonin, and matrix metalloproteinase 2. CONCLUSIONS: Hypoxia interferes with TGFbeta signaling in macrophages by calpain-mediated proteolysis of the central signaling component SMAD2. PMID- 26146545 TI - Dendrimer Conjugates for Light-activated Delivery of Antisense Oligonucleotides. AB - Therapeutic oligonucleotides, such as splice switching ONs (SSOs), provide opportunities for treating serious, life-threatening diseases. However, the development of ONs as therapeutic agents has progressed slowly, because difficult cytosolic delivery of SSOs into the cytosol and nucleus remains a major barrier. Photochemical internalization (PCI), a promising strategy for endosomal escape, was introduced to disrupt the endosomal membrane using light and a photosensitizer. Here we constructed Poly(amido amine) (PAMAM) dendrimer conjugates to simultaneously deliver SSOs and photosensitizers into endo/lysosomal compartments. After photo-irradiation, considerable ONs were observed to diffuse into the cytosol and accumulate in the nucleus. Furthermore, the PCI mediated cytosolic delivery of SSOs effectively enhanced their nuclear splice switching activity. PMID- 26146546 TI - Presentation Modality of Glycoconjugates Modulates Dendritic Cell Phenotype. AB - The comparative dendritic cell (DC) response to glycoconjugates presented in soluble, phagocytosable, or non-phagocytosable display modalities is poorly understood. This is particularly problematic, as the probing of immobilized glycans presented on the surface of microarrays is a common screen for potential candidates for glycan-based therapeutics. However, the assumption that carbohydrate-protein interactions on a flat surface can be translatable to development of efficacious therapies, such as vaccines, which are delivered in soluble or phagocytosable particles, has not been validated. Thus, a preliminary investigation was performed in which mannose or glucose was conjugated to cationized bovine serum albumin and presented to DCs in soluble, phagocytosable, or non-phagocytosable display modalities. The functional DC response to the glycoconjugates was assessed via a high throughput assay. Dendritic cell phenotypic outcomes were placed into a multivariate, general linear model (GLM) and shown to be statistically different amongst display modalities when comparing similar surface areas. The GLM showed that glycoconjugates that were adsorbed to wells were the most pro-inflammatory while soluble conjugates were the least. DC interactions with mannose conjugates were found to be calcium dependent and could be inhibited via anti-DC-SIGN antibodies. The results of this study aim to resolve conflicts in reports from multiple laboratories showing differential DC profiles in response to similar, if not identical, ligands delivered via different modalities. Additionally, this study begins to bridge the gap between microarray binding data and functional cell responses by highlighting the phenotypes induced from adsorbed glycoconjugates as compared to those in solution or displayed on microparticles. PMID- 26146547 TI - Elastomeric nanocomposite scaffolds made from poly (glycerol sebacate) chemically crosslinked with carbon nanotubes. AB - Carbon nanotube (CNT)-based nanocomposites often possess properties such as high stiffness, electrical conductivity, and thermal stability and have been studied for various biomedical and biotechnological applications. However, the current design approaches utilize CNTs as physical filler, and thus, the true potential of CNT-based nanocomposites has not been achieved. Here, we introduce a general approach of fabricating stiff, elastomeric nanocomposites from poly(glycerol sebacate) (PGS) and CNTs. The covalent crosslinking between the nanotubes and polymer chains resulted in novel property combinations that are not observed in conventional nanocomposites. The addition of 1% CNTs resulted a five-fold increase in the tensile modulus and a six-fold increase in compression modulus compared with PGS alone, which is far superior to the previously reported studies for CNT-based nanocomposites. Despite significant increase in mechanical stiffness, the elasticity of the network was not compromised and the resulting nanocomposites showed more than 94% recovery. This study demonstrates that the chemical conjugation of CNTs to a PGS backbone results in stiff and elastomeric nanocomposites. Additionally, in vitro studies using human mesenchymal stem cells (hMSCs) indicated that the incorporation of CNTs to PGS network significantly enhanced the differentiation potential of the seeded hMSCs rendering them potentially suitable for applications ranging from scaffolding in musculoskeletal tissue engineering to biosensors in biomedical devices. PMID- 26146548 TI - Micro- and Nanoparticles for Treating Cardiovascular Disease. AB - Cardiovascular disease, including myocardial infarction (MI) and peripheral artery disease (PAD), afflicts millions of people in Unites States. Current therapies are insufficient to restore blood flow and repair the injured heart or skeletal muscle, respectively, which is subjected to ischemic damage following vessel occlusion. Micro- and nano-particles are being designed as delivery vehicles for growth factors, enzymes and/or small molecules to provide a sustained therapeutic stimulus at the injured tissue. Depending on the formulation, the particles can be injected directly into the heart or skeletal muscle, or accumulate at the site of injury following an intravenous injection. In this article we review existing particle based therapies for treating MI and PAD. PMID- 26146549 TI - Elastin-based biomaterials and mesenchymal stem cells. AB - Elastin is the dominant mammalian elastic protein found in soft tissue. Elastin based biomaterials have the potential to repair elastic tissues by improving local elasticity and providing appropriate cellular interactions and signaling. Studies that combine these biomaterials with mesenchymal stem cells have demonstrated their capacity to also regenerate non-elastic tissue. Mesenchymal stem cell differentiation can be controlled by their immediate environment, and their sensitivity to elasticity makes them an ideal candidate for combining with elastin-based biomaterials. With the growing accessibility of the elastin precursor, tropoelastin, and elastin-derived materials, the amount of research interest in combining these two fields has increased and, subsequently, is leading to the realization of a potentially new strategy for regenerative medicine. PMID- 26146550 TI - Shape Control in Engineering of Polymeric Nanoparticles for Therapeutic Delivery. AB - Nanoparticle-mediated delivery of therapeutics holds great potential for the diagnosis and treatment of a wide range of diseases. Significant advances have been made in the design of new polymeric nanoparticle carriers through modulation of their physical and chemical structures and biophysical properties. Nanoparticle shape has been increasingly proposed as an important attribute dictating their transport properties in biological milieu. In this review, we highlight three major methods for preparing polymeric nanoparticles that allow for exquisite control of particle shape. Special attention is given to various approaches to controlling nanoparticle shape by tuning copolymer structural parameters and assembly conditions. This review also provides comparisons of these methods in terms of their unique capabilities, materials choices, and specific delivery cargos, and summarizes the biological effects of nanoparticle shape on transport properties at the tissue and cellular levels. PMID- 26146551 TI - Redox-Responsive Self-Assembled Chain-Shattering Polymeric Therapeutics. AB - We report the design and development of redox-responsive chain-shattering polymeric therapeutics (CSPTs). CSPTs were synthesized by condensation polymerization and further modified with poly(ethylene glycol) (PEG) via "Click" reaction. Size-controlled CSPT nanoparticles (NPs) were formed through nanoprecipitation with high drug loading (up to 18%); the particle size increased in a concentration dependent manner. Drug release from particles was well controlled over 48 h upon redox triggering. The anticancer efficacy of the CSPT NPs was validated both in vitro and in vivo. PMID- 26146552 TI - Balancing polymer hydrophobicity for ligand presentation and siRNA delivery in dual function CXCR4 inhibiting polyplexes. AB - In the present study, a series of copolymers (PAMD-Ch) was synthesized by grafting polymeric Plerixafor/AMD3100 (PAMD) with different amounts of cholesterol and the effect of cholesterol modification on siRNA delivery was investigated. PAMD-Ch/siRNA polyplexes exhibited improved colloidal and enzymatic stability when compared with PAMD/siRNA polyplexes containing no cholesterol. PAMD-Ch with low (17 wt%) and medium (25 wt%) cholesterol content exhibited CXCR4 antagonism comparable to unmodified PAMD. Cholesterol modification increased cell uptake of siRNA polyplexes and significantly decreased sensitivity of siRNA transfection to the presence of serum. When used to deliver anticancer siRNA against polo-like kinase 1 (PLK1), polyplexes based on PAMD-Ch with 17 wt% cholesterol exhibited the highest cancer cell killing activity both in serum-free and serum-containing conditions. Overall, the results of this study validate cholesterol modified PAMD as dual-function delivery vectors suitable for efficient delivery of anticancer siRNA and simultaneous CXCR4 inhibition for combined anticancer therapies. PMID- 26146554 TI - Beirut Air Pollution and Health Effects - BAPHE study protocol and objectives. AB - BACKGROUND: Recent studies investigating the health effects of air pollution have proven an existing impact around and below international air quality guidelines and standards. These studies were based on accessible data from official registers managed by public authorities. The protocol followed in BAPHE project is described; its benefits and disadvantages are presented and discussed in this paper. METHODS: Based on the review of several international studies we developed a custom made approach in BAPHE (Beirut Air Pollution and Health Effects) project in order to analyze the short term health effects of air pollution taking into consideration the lack of data availability from official sources. RESULTS: PM2.5 and PM10 concentrations were measured in Beirut for the period starting from the 1(st) of January 2012 to the 31(st) of December 2012. The annual average concentrations of PM10 and PM2.5 exceeded WHO's annual average limits by 150 % and 200 %, respectively. Health data for 11,567 individuals were collected over 12 months. A variation of hospital admission causes was observed by age categories and gender. CONCLUSIONS: This article presents a simple protocol and the descriptive results of its application in the frame of an eco-epidemiological study in Lebanon. We believe that this work is not only important on a local scale, but it could be helpful for environmental epidemiological studies in other countries. PMID- 26146553 TI - Epidemiological situation of Lyme borreliosis in Belgium, 2003 to 2012. AB - BACKGROUND: Some studies show that the incidence of Lyme borreliosis is increasing in different European countries. In order to evaluate if this is also the case in Belgium, different data sources were consulted to describe the epidemiology of Lyme borreliosis in the country during the last decade. METHODS: Data from two databases were analyzed for the time period 2003-2010 and 2003-2012 for respectively: the registration of minimal clinical data from Belgian hospitals (principal and secondary diagnosis), and a sentinel laboratory network reporting positive laboratory results. RESULTS: The number of hospitalized cases per year remained stable between 2003 and 2010, ranging from 970 (in 2008) to 1453 (in 2006), with a median of 1132.5 cases per year. Between 2003 and 2012, yearly fluctuations in the number of positive tests were reported by the sentinel laboratory network (with a minimum of 996 positive tests in 2007 and a maximum of 1651 positive tests in 2005), but there is no increasing trend over the study period (median = 1200.5 positive tests per year). The highest incidence rates of hospitalization and the highest reported incidence of positive laboratory results are registered in the provinces of Luxemburg, Limburg, Flemish Brabant and Antwerp, with a typical seasonal pattern (peak in September). The age groups affected most are those from 5 to 14 years and 45 to 69. CONCLUSION: Based on hospital records and laboratory results, no increasing trend in Lyme disease was observed over the 2003-2012 period in Belgium. These results are in line with the stable incidence of erythema migrans reported by a sentinel network of general practitionners between 2003 and 2009. Multi-source surveillance of vector-borne diseases should be further implemented. PMID- 26146555 TI - Dysfunctional metacognition and drive for thinness in typical and atypical anorexia nervosa. AB - BACKGROUND: Anorexia nervosa is complex and difficult to treat. In cognitive therapies the focus has been on cognitive content rather than process. Process oriented therapies may modify the higher level cognitive processes of metacognition, reported as dysfunctional in adult anorexia nervosa. Their association with clinical features of anorexia nervosa, however, is unclear. With reclassification of anorexia nervosa by DSM-5 into typical and atypical groups, comparability of metacognition and drive for thinness across groups and relationships within groups is also unclear. Main objectives were to determine whether metacognitive factors differ across typical and atypical anorexia nervosa and a non-clinical community sample, and to explore a process model by determining whether drive for thinness is concurrently predicted by metacognitive factors. METHODS: Women receiving treatment for anorexia nervosa (n = 119) and non-clinical community participants (n = 100), aged between 18 and 46 years, completed the Eating Disorders Inventory (3(rd) Edition) and Metacognitions Questionnaire (Brief Version). Body Mass Index (BMI) of 18.5 kg/m(2) differentiated between typical (n = 75) and atypical (n = 44) anorexia nervosa. Multivariate analyses of variance and regression analyses were conducted. RESULTS: Metacognitive profiles were similar in both typical and atypical anorexia nervosa and confirmed as more dysfunctional than in the non-clinical group. Drive for thinness was concurrently predicted in the typical patients by the metacognitive factors, positive beliefs about worry, and need to control thoughts; in the atypical patients by negative beliefs about worry and, inversely, by cognitive self-consciousness, and in the non-clinical group by cognitive self-consciousness. CONCLUSIONS: Despite having a healthier weight, the atypical group was as severely affected by dysfunctional metacognitions and drive for thinness as the typical group. Because metacognition concurrently predicted drive for thinness in both groups, a role for process-oriented therapy in adults is suggested. Implications are discussed. PMID- 26146556 TI - Ultrasound field characterization and bioeffects in multiwell culture plates. AB - BACKGROUND: Ultrasound with frequencies in the kilohertz range has been demonstrated to promote biological effects and has been suggested as a non invasive tool for tissue healing and repair. However, many challenges exist to characterize and develop kilohertz ultrasound for therapy. In particular there is a limited evidence-based guidance and standard procedure in the literature concerning the methodology of exposing biological cells to ultrasound in vitro. METHODS: This study characterized a 45-kHz low-frequency ultrasound at three different preset intensity levels (10, 25, and 75 mW/cm(2)) and compared this with the thermal and biological effects seen in a 6-well culture setup using murine odontoblast-like cells (MDPC-23). Ultrasound was produced from a commercially available ultrasound-therapy system, and measurements were recorded using a needle hydrophone in a water tank. The transducer was displaced horizontally and vertically from the hydrophone to plot the lateral spread of ultrasound energy. Calculations were performed using Fourier transform and average intensity plotted against distance from the transducer. During ultrasound treatment, cell cultures were directly exposed to ultrasound by submerging the ultrasound transducer into the culture media. Four groups of cell culture samples were treated with ultrasound. Three with ultrasound at an intensity level of 10, 25, and 75 mW/cm(2), respectively, and the final group underwent a sham treatment with no ultrasound. Cell proliferation and viability were analyzed from each group 8 days after three ultrasound treatments, each separated by 48 h. RESULTS: The ultrasonic output demonstrated considerable lateral spread of the ultrasound field from the exposed well toward the adjacent culture wells in the multiwell culture plate; this correlated well with the dose-dependent increase in the number of cultured cells where significant biological effects were also seen in adjacent untreated wells. Significant thermal variations were not detected in adjacent untreated wells. CONCLUSIONS: This study highlights the pitfalls of using multiwell plates when investigating the biological effect of kilohertz low frequency ultrasound on adherent cell cultures. PMID- 26146557 TI - Characterization and evaluation of tissue-mimicking gelatin phantoms for use with MRgFUS. AB - BACKGROUND: A tissue-mimicking phantom that accurately represents human-tissue properties is important for safety testing and for validating new imaging techniques. To achieve a variety of desired human-tissue properties, we have fabricated and tested several variations of gelatin phantoms. These phantoms are simple to manufacture and have properties in the same order of magnitude as those of soft tissues. This is important for quality-assurance verification as well as validation of magnetic resonance-guided focused ultrasound (MRgFUS) treatment techniques. METHODS: The phantoms presented in this work were constructed from gelatin powders with three different bloom values (125, 175, and 250), each one allowing for a different mechanical stiffness of the phantom. Evaporated milk was used to replace half of the water in the recipe for the gelatin phantoms in order to achieve attenuation and speed of sound values in soft tissue ranges. These acoustic properties, along with MR (T1 and T2*), mechanical (density and Young's modulus), and thermal properties (thermal diffusivity and specific heat capacity), were obtained through independent measurements for all three bloom types to characterize the gelatin phantoms. Thermal repeatability of the phantoms was also assessed using MRgFUS and MR thermometry. RESULTS: All the measured values fell within the literature-reported ranges of soft tissues. In heating tests using low-power (6.6 W) sonications, interleaved with high-power (up to 22.0 W) sonications, each of the three different bloom phantoms demonstrated repeatable temperature increases (10.4 +/- 0.3 degrees C for 125-bloom, 10.2 +/- 0.3 degrees C for 175-bloom, and 10.8 +/- 0.2 degrees C for 250-bloom for all 6.6-W sonications) for heating durations of 18.1 s. CONCLUSION: These evaporated milk-modified gelatin phantoms should serve as reliable, general soft tissue mimicking MRgFUS phantoms. PMID- 26146558 TI - Learning aptitude, spatial orientation and cognitive flexibility tested in a virtual labyrinth after virtual stress induction. AB - BACKGROUND: Under stressful conditions such as in an emergency situation, efficient information processing is essential for reasonable responses. PURPOSE OF THE STUDY: Virtual Reality (VR) technology is used to induce stress and to test three main cognitive functions for decision making in stressful situations. METHODS: A VR task was developed to induce stress following the Trier Social Stress Test (TSST) protocol and two VR cognitive performance tests to measure learning aptitude, spatial orientation and cognitive flexibility. Participants (N = 31) gave a public speech in front of a virtual audience (TSST) and later had to find their way out of different VR labyrinths. The first exercise tested spatial orientation and learning aptitude where participants had to learn aspects of the ground layout and geometric icons had to be identified as correct in order to be able to exit. The second labyrinth tested cognitive flexibility on the background of the Wisconsin Card Sorting Test. STATISTICAL TESTS: Correlations were analyzed using Kendall Tau Correlation (One-tailed tests with p set to 0.05 for all analyses). Heart rate (HR) was calculated from the RR time values and averaged across the TSST- speech and the post-stress period. Autonomic nervous system reactivity was defined as the deviation of HR during TSST- speech condition from post-stress baseline measurement. A repeated-measures t-test was used to analyze differences. RESULTS: The newly developed virtual stress test was successfully adapted from the original TSST. Participants perceived the task as stressful and scored an average of 5.7 points on a 1-8 Likert Scale. As a physiological stress parameter, increased heart rates of the participants showed that they were more stressed during the TSST procedure compared to the post-stress period. Also, the subjective stress perception, has a strong correlation with the results of the cognitive tasks performed after the stress induction. CONCLUSIONS: The more a participant experienced the TSST as stressful, the lower their learning aptitude and spatial orientation were found to be at the end of the study. On the other hand, if someone perceived the virtual TSST as "unexpected", as an indicator for a mild stress response, their cognitive flexibility was improved. Potential Implications: The findings indicate that both, the VR stress induction scenario using TSST, as well as the VR cognitive tests, are a first successful step towards a better ecological validity in neuropsychological testing. PMID- 26146560 TI - Detection of BCR-ABL T315I mutation by peptide nucleic acid directed PCR clamping and by peptide nucleic acid FISH. AB - BACKGROUND: Mutations of the BCR-ABL1 fusion gene represent a well established cause of resistance to tyrosine kinase inhibitors. Among the different mutations identified T315I is of particular concern since it is not effectively targeted by the majority of Tyrosine Kinase Inhibitors so far available. We developed a novel assay based on peptide nucleic acid (PNA) technology coupled to immunofluorescence microscopy (PNA-FISH) for the specific detection at a single cell level of BCR-ABL (T315I) mutation thus improving both, diagnostic resolution and the study of clonal prevalence. Furthermore we developed an additional method based on PNA directed PCR-clamping for the fast and easy detection of the mutation. RESULTS: The PNA directed PCR clamping allows to detect an amount of mutated template as low as 0.5 %. This method is highly sensitive, specific and cheap and could be applied even in laboratory not equipped for more sophisticated analysis. Furthermore, the PNA FISH method allows to identify a small amount of progenitor cells still present after therapy with specific inhibitors. CONCLUSIONS: We present here two different methods based on PNA for the detection of T315I useful for different purposes. PNA-FISH can be used to study clonal evolution. In addition, this method could help in the study of compound mutations being able to identify two different mutations in a single cell. PNA directed PCR clamping although not superior to sequencing can be applied worldwide even in laboratory not equipped to search for mutations. PMID- 26146559 TI - Carbon Nanotube Uptake Changes the Biomechanical Properties of Human Lung Epithelial Cells in a Time-dependent Manner. AB - The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial properties and the exposure duration. Herein we used a multi tier strategy to investigate the relationship between user-characterized multi walled carbon nanotubes (MWCNTs) exposure duration and their induced biochemical and biomechanical effects on model human lung epithelial cells (BEAS-2B). Our results showed that exposure to MWCNTs leads to time-dependent intracellular uptake and generation of reactive oxygen species (ROS), along with time-dependent gradual changes in cellular biomechanical properties. In particular, the amount of internalized MWCNTs followed a sigmoidal curve with the majority of the MWCNTs being internalized within 6h of exposure; further, the sigmoidal uptake correlated with the changes in the oxidative levels and cellular biomechanical properties respectively. Our study provides new insights into the time-dependent induced toxicity caused by exposure to occupationally relevant doses of MWCNTs and could potentially help establish bases for early risk assessments of other nanomaterials toxicological profiles. PMID- 26146561 TI - Urinary biomarkers for early diabetic nephropathy in type 2 diabetic patients. AB - Diabetic nephropathy (DN) is a serious complication of diabetes associated with increased risk of mortality, and cardiovascular and renal outcomes. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney function and improve patient outcomes. Urinary biomarkers may be elevated in diabetic patients even before the appearance of microalbuminuria, and can be used as useful marker for detecting nephropathy in patients with normoalbuminuria (early DN). We reviewed some new and important urinary biomarkers, such as: Neutrophil gelatinase associated lipocalin (NGAL), N-acetyl beta-glucosaminidase (NAG), Cystatin C, alpha 1-microglobulin, immunoglobulin G or M, type IV collagen, nephrin, angiotensinogen and liver-type fatty acid binding protein (L-FABP) associated with early DN in type 2 diabetic patients. Our search identified a total of 42 studies that have been published to date. Urinary levels of these biomarkers were elevated in type 2 diabetic patients compared with non-diabetic controls, including in patients who had no signs indicating nephropathy (without microalbuminuria), and showed positive correlation with albuminuria. Despite the promise of these new urinary biomarkers, further large, multicenter prospective studies are still needed to confirm their clinical utility as a screening tool for early type 2 DN in every day practice. PMID- 26146562 TI - Clinical endocrinological evaluation of the gonadal axis (testosterone, LH and FSH) in prostate cancer patients switched from a GnRH antagonist to a LHRH agonist. AB - OBJECTIVES: To investigate the levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prostate-specific antigen (PSA) in prostate cancer patients before and after the switch from degarelix to leuprolide treatments. METHODS: We enrolled 40 treatment-naive prostate cancer patients who were treated initially with degarelix and were later switched to leuprolide. The subjects were divided into three groups depending on when they were switched to leuprolide: the 3-month group (3m; switched after 84 days, n=10), the 2-month group (2m; 56 days, n=10), and the 1-month group (1m; 28 days, n=20). Patient symptoms and hormone levels were measured after switching therapy. The castration level was defined as a serum testosterone level <=50 ng/dl. RESULTS: Thirty-nine subjects (97.5%) achieved castration levels of testosterone (11+/-5.8 ng/dl) 2 weeks after degarelix was first administered, and the characteristics of these patients were investigated. Testosterone levels increased and exceeded the castration level in one subject each of the 3m (142 ng/dl), 2m (72 ng/dl), and 1m groups (63 ng/dl). All subjects achieved the castration level by day 5. In contrast to testosterone levels, the LH and FSH surge on day 2 was significantly higher in the 1m group than in the other groups. The clinical symptoms were not exacerbated before or after switching in any patients. CONCLUSIONS: A testosterone surge was observed in 8.3 % of the study patients; however, it was very short-lived and mild. LH and FSH levels were significantly higher 1 month after administration compared with 2 or 3 months after degarelix administration. PMID- 26146563 TI - Antifungal therapy in patients with pulmonary Candida spp. colonization may have no beneficial effects. AB - BACKGROUND: In critically ill patients, Candida spp. can often be identified in pulmonary samples. The impact of prompt antifungal therapy in these patients is unknown. METHODS: In this retrospective study, 500 adult patients with pulmonary Candida spp. colonization admitted to the intensive care unit (ICU) between 2010 and 2012 were included. The patients were analyzed according to whether or not they received antifungal therapy, which was administered at the discretion of the attending physician. Logistic regression analysis was performed to investigate the impact of antifungal therapy on hospital mortality and new onset of ventilator-associated pneumonia. In a stepwise backward elimination, the impact of age, cancer as an underlying disease, Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA) score were considered. RESULTS: After excluding 178 patients with multifocal Candida spp., isolated pulmonary Candida spp. colonization was found in 322 patients (cohort 1). Pre existing pneumonia was found in 147/322 patients. Out of the remaining 175 patients (cohort 2), 44 patients received any antifungal therapy, and 131 were defined as the control group. Patients who received antifungal therapy had higher hospital mortality (50 vs. 30 %, p = 0.02) and pneumonia rates (47.7 vs. 16.8 %; p < 0.001) than those who did not. In Cox regression analysis, antifungal therapy was not independently associated with favorable outcome (mortality: odds ratio 0.854 (95 % CI 0.467-1.561); new pneumonia: 1.048 (0.536-2.046)), but SAPS II and SOFA score were significantly (p < 0.05) independent covariates for worse outcome. CONCLUSIONS: In critically ill patients with pulmonary Candida spp. colonization, antifungal therapy may not have an impact on the incidence of new pneumonia or in-hospital mortality after adjustment for confounders. PMID- 26146564 TI - Is a threshold-based model a superior method to the relative percent concept for establishing individual exercise intensity? a randomized controlled trial. AB - BACKGROUND: Exercise intensity is arguably the most critical component of the exercise prescription model. It has been suggested that a threshold based model for establishing exercise intensity might better identify the lowest effective training stimulus for all individuals with varying fitness levels; however, experimental evidence is lacking. The purpose of this study was to compare the effectiveness of two exercise training programs for improving cardiorespiratory fitness: threshold based model vs. relative percent concept (i.e., % heart rate reserve - HRR). METHODS: Apparently healthy, but sedentary men and women (n = 42) were randomized to a non-exercise control group or one of two exercise training groups. Exercise training was performed 30 min/day on 5 days/week for 12weeks according to one of two exercise intensity regimens: 1) a relative percent method was used in which intensity was prescribed according to percentages of heart rate reserve (HRR group), or 2) a threshold based method (ACE-3ZM) was used in which intensity was prescribed according to the first ventilatory threshold (VT1) and second ventilatory threshold (VT2). RESULTS: Thirty-six men and women completed the study. After 12weeks, VO2max increased significantly (p < 0.05 vs. controls) in both HRR (1.76 +/- 1.93 mL/kg/min) and ACE-3ZM (3.93 +/- 0.96 mL/kg/min) groups. Repeated measures ANOVA identified a significant interaction between exercise intensity method and change in VO2max values (F = 9.06, p < 0.05) indicating that VO2max responded differently to the method of exercise intensity prescription. In the HRR group 41.7 % (5/12) of individuals experienced a favorable change in relative VO2max (Delta > 5.9 %) and were categorized as responders. Alternatively, exercise training in the ACE-3ZM group elicited a positive improvement in relative VO2max (Delta > 5.9 %) in 100 % (12/12) of the individuals. CONCLUSIONS: A threshold based exercise intensity prescription: 1). elicited significantly (p < 0.05) greater improvements in VO2max, and 2). attenuated the individual variation in VO2max training responses when compared to relative percent exercise training. These novel findings are encouraging and provide important preliminary data for the design of individualized exercise prescriptions that will enhance training efficacy and limit training unresponsiveness. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ID NCT02351713 Registered 30 January 2015. PMID- 26146565 TI - Distal and Proximal Religiosity as Protective Factors for Adolescent and Emerging Adult Alcohol Use. AB - Data from emerging adults (ages 18-29, N = 900) in the National Comorbidity Survey Replication Study was used to examine the influence of childhood and emerging adult religiosity and religious-based decision-making, and childhood adversity, on alcohol use. Childhood religiosity was protective against early alcohol use and progression to later abuse or dependence, but did not significantly offset the influence of childhood adversity on early patterns of heavy drinking in adjusted logistic regression models. Religiosity in emerging adulthood was negatively associated with alcohol use disorders. Protective associations for religiosity varied by gender, ethnicity and childhood adversity histories. Higher religiosity may be protective against early onset alcohol use and later development of alcohol problems, thus, should be considered in prevention programming for youth, particularly in faith-based settings. Mental health providers should allow for integration of clients' religiosity and spirituality beliefs and practices in treatment settings if clients indicate such interest. PMID- 26146567 TI - A Comparative Study of the Metabolic and Skeletal Response of C57BL/6J and C57BL/6N Mice in a Diet-Induced Model of Type 2 Diabetes. AB - Type 2 diabetes mellitus (T2DM) represents a complex clinical scenario of altered energy metabolism and increased fracture incidence. The C57BL/6 mouse model of diet-induced obesity has been used to study the mechanisms by which altered glucose homeostasis affects bone mass and quality, but genetic variations in substrains of C57BL/6 may have confounded data interpretation. This study investigated the long-term metabolic and skeletal consequences of two commonly used C57BL/6 substrains to a high fat (HF) diet. Male C57BL/6J, C57BL/6N, and the negative control strain, C3H/HeJ, mice were fed a control or HF diet for 24 wks. C57BL/6N mice on a HF diet demonstrated an increase in plasma insulin and blood glucose as early as 4 wk, whereas these responses were delayed in the C57BL/6J mice. The C57BL/6N mice exhibited more severe hepatic steatosis and inflammation. Only the C57BL/6N mice lost significant trabecular bone in response to the high fat diet. The C3H/HeJ mice were protected from bone loss. The data show that C57BL/6J and C57BL/6N mice differ in their metabolic and skeletal response when fed a HF diet. These substrain differences should be considered when designing experiments and are likely to have implications on data interpretation and reproducibility. PMID- 26146568 TI - Feasibility and Initial Performance of Simultaneous SPECT-CT Imaging Using a Commercial Multi-Modality Preclinical Imaging System. AB - Multi-modality imaging provides coregistered PET-CT and SPECT-CT images; however such multi-modality workflows usually consist of sequential scans from the individual imaging components for each modality. This typical workflow may result in long scan times limiting throughput of the imaging system. Conversely, acquiring multi-modality data simultaneously may improve correlation and registration of images, improve temporal alignment of the acquired data, increase imaging throughput, and benefit the scanned subject by minimizing time under anesthetic. In this work, we demonstrate the feasibility and procedure for modifying a commercially available preclinical SPECT-CT platform to enable simultaneous SPECT-CT acquisition. We also evaluate the performance of simultaneous SPECT-CT tomographic imaging with this modified system. Performance was accessed using a (57)Co source and image quality was evaluated with (99m)Tc phantoms in a series of simultaneous SPECT-CT scans. PMID- 26146566 TI - Role of Peroxisome Proliferator-Activated Receptor gamma in Ocular Diseases. AB - Peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the nuclear receptor superfamily, is a ligand-activated transcription factor that plays an important role in the control of a variety of physiological processes. The last decade has witnessed an increasing interest for the role played by the agonists of PPAR gamma in antiangiogenesis, antifibrosis, anti-inflammation effects and in controlling oxidative stress response in various organs. As the pathologic mechanisms of major blinding diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), keratitis, and optic neuropathy, often involve neoangiogenesis and inflammation- and oxidative stress-mediated cell death, evidences are accumulating on the potential benefits of PPAR gamma to improve or prevent these vision threatening eye diseases. In this paper we describe what is known about the role of PPAR gamma in the ocular pathophysiological processes and PPAR gamma agonists as novel adjuvants in the treatment of eye diseases. PMID- 26146569 TI - Cellular Plasticity in Prostate Cancer Bone Metastasis. AB - Purpose. Experimental data suggest that tumour cells can reversibly transition between epithelial and mesenchymal states (EMT and MET), a phenomenon known as cellular plasticity. The aim of this review was to appraise the clinical evidence for the role of cellular plasticity in prostate cancer (PC) bone metastasis. Methods. An electronic search was performed using PubMed for studies that have examined the differential expression of epithelial, mesenchymal, and stem cell markers in human PC bone metastasis tissues. Results. The review included nineteen studies. More than 60% of the studies used <=20 bone metastasis samples, and there were several sources of heterogeneity between studies. Overall, most stem cell markers analysed, except for CXCR4, were positively expressed in bone metastasis tissues, while the expression of EMT and MET markers was heterogeneous between and within samples. Several EMT and stemness markers that are involved in osteomimicry, such as Notch, Met receptor, and Wnt/beta pathway, were highly expressed in bone metastases. Conclusions. Clinical findings support the role of cellular plasticity in PC bone metastasis and suggest that epithelial and mesenchymal states cannot be taken in isolation when targeting PC bone metastasis. The paper also highlights several challenges in the clinical detection of cellular plasticity. PMID- 26146571 TI - A Complicated Case of Triple Valve Infective Endocarditis in an IV Drug User with a Bicuspid Aortic Valve Requiring Three Separate Salvage Operations: A Case Report and Literature Review. AB - Infective endocarditis (IE) is an infection of the endocardium that involves valves and adjacent mural endocardium or a septal defect. Local complications include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial abscesses. If left untreated, IE is generally fatal. Diagnosing IE can be straightforward in patients with the typical oslerian manifestations such as bacteremia, evidence of active valvulitis, peripheral emboli, and immunologic vascular phenomena. In the acute course, however, the classic peripheral stigmata may be few or absent, particularly among intravenous drug abuse (IVDA) patients in whom IE is often due to a S. aureus infection of right-sided heart valves. We present a complicated case of a very aggressive native aortic valve MSSA (methicillin sensitive Staphylococcus aureus) IE in a young adult male with a past medical history of bicuspid aortic valve and IV drug abuse. His clinical course was complicated by aortic valve destruction and development of third-degree AV block, as well as an aorto-left atrial fistula requiring emergent operation for AV replacement and patch repair. The patient required two reoperations for recurrent endocarditis and its complications. PMID- 26146572 TI - Fibromuscular Dysplasia Leading to Spontaneous Coronary Artery Dissection with Sudden Cardiac Arrest. AB - A 30-year-old previously healthy female, who was six-week postpartum, experienced sudden collapse and tonic-clonic seizure. Emergency medicine services arrived at the scene and the patient was found to be in ventricular fibrillation. Advanced cardiovascular life support (ACLS) was initiated with return of spontaneous circulation. Afterwards, her initial EKG showed atrial fibrillation with rapid ventricular rate, ST elevation in leads II, III, and aVF, and ST depression in V2 V4. She was transferred to a tertiary care hospital where emergent angiogram was performed revealing obstruction of blood flow in the proximal and mid right coronary artery (RCA). A hazy and irregularly contoured appearance of the RCA was consistent with diagnosis of fibromuscular dysplasia. Subsequently, intravascular ultrasonogram (IVUS) was performed which confirmed the diagnosis of RCA dissection. Successful revascularization of the RCA was performed using two bare mental stents. After a complicated course in hospital, she was discharged in stable condition and did very well overall. PMID- 26146570 TI - alpha7 Nicotinic Receptor Promotes the Neuroprotective Functions of Astrocytes against Oxaliplatin Neurotoxicity. AB - Neuropathies are characterized by a complex response of the central nervous system to injuries. Glial cells are recruited to maintain neuronal homeostasis but dysregulated activation leads to pain signaling amplification and reduces the glial neuroprotective power. Recently, we highlighted the property of alpha7 nicotinic-acetylcholine-receptor (nAChR) agonists to relieve pain and induce neuroprotection simultaneously with a strong increase in astrocyte density. Aimed to study the role of alpha7 nAChR in the neuron-glia cross-talk, we treated primary rat neurons and astrocytes with the neurotoxic anticancer drug oxaliplatin evaluating the effect of the alpha7 nAChR agonist PNU-282987 (PNU). Oxaliplatin (1 MUM, 48 h) reduced cell viability and increased caspase-3 activity of neuron monocultures without damaging astrocytes. In cocultures, astrocytes were not able to protect neurons by oxaliplatin even if glial cell metabolism was stimulated (pyruvate increase). On the contrary, the coculture incubation with 10 MUM PNU improved neuron viability and inhibited apoptosis. In the absence of astrocytes, the protection disappeared. Furthermore, PNU promoted the release of the anti-inflammatory cytokine TGF-beta1 and the expression of the glutamate detoxifying enzyme glutamine synthetase. The alpha7 nAChR stimulation protects neurons from oxaliplatin toxicity through an astrocyte-mediated mechanism. alpha7 nAChR is suggested for recovering the homeostatic role of astrocytes. PMID- 26146573 TI - Multidisciplinary Management of Complicated Crown-Root Fracture of an Anterior Tooth Undergoing Apexification. AB - The purpose of this case report was to present the multidisciplinary management of a subgingival crown-root fracture of a patient undergoing apexification treatment. A 12-year-old male patient was referred to the pediatric dentistry clinic with an extensive tooth fracture of the right permanent maxillary lateral incisor. Clinical and radiographic examinations revealed the presence of a complicated crown-root fracture, which had elongated to the buccal subgingival area. The dental history disclosed that the apexification procedure had been started to be performed after his first trauma experience and he had neglected his appointment. The coronal fragment was gently extracted; endodontic treatment was performed; flap surgery was performed to make the fracture line visible. The coronal fragment was reattached to the root fragment with a dual-cure luting composite. A fiber post was stabilized and the access cavity of the tooth was restored with composite resin. At the end of the 24th month, the tooth was asymptomatic, functionally, esthetically acceptable and had no periapical pathology. It is important for the patients undergoing apexification treatment to keep their appointments because of the fracture risk. Restoration of the fractured tooth by preparing retention grooves and a bonding fiber-reinforced post are effective and necessary approaches for successful management. PMID- 26146574 TI - Familial Abdominal and Intestinal Lipomatosis Presenting with Upper GI Bleeding. AB - Although lipomas are encapsulated benign tumors, systemic lipomatosis defines infiltrative nonencapsulated tumors resembling normal adipose tissue. Abdominal lipomatosis and intestinal lipomatosis are different clinicopathological entities with similar clinical symptoms. We describe here a case presenting with upper gastrointestinal bleeding from eroded submucosal lipoma at duodenum secondary to intestinal lipomatosis and abdominal lipomatosis. PMID- 26146575 TI - Primary Bronchopulmonary Actinomycosis Masquerading as Lung Cancer: Apropos of Two Cases and Literature Review. AB - Actinomycosis is a rare and slowly progressive infectious disease that can affect a variety of organ systems including the lung. It is caused by filamentous Gram positive anaerobic bacteria of the genus Actinomyces. Despite its rarity, pulmonary actinomycosis can involve lung parenchyma, bronchial structures, and chest wall. The disease can mimic lung malignancy given its nonspecific clinical and radiological presentation, thus posing a diagnostic dilemma to the attending physician. In this paper, we describe two patients with pulmonary actinomycosis mimicking bronchogenic carcinoma; the former presented with peripheral infiltrate and associated hilar/mediastinal lymphadenopathy and the latter presented with a foreign body-induced endobronchial mass. Clinical, imaging, diagnostic, and therapeutical aspects of the disease are discussed, demonstrating the paramount importance of the histological examination of lung tissue specimens in the confirmation of the infection given either its low culture yield or the limited use of new molecular diagnostic tools in routine clinical practice. PMID- 26146576 TI - Progressive Intracranial Vertebral Artery Dissection Presenting with Isolated Trigeminal Neuralgia-Like Facial Pain. AB - Intracranial vertebral artery dissection (IVAD) is a potentially life-threatening disease, which usually presents with ischemic stroke or subarachnoid hemorrhage. IVAD presenting with isolated facial pain is rare, and no case with isolated trigeminal neuralgia- (TN-) like facial pain has been reported. Here, we report the case of a 57-year-old male with IVAD who presented with acute isolated TN like facial pain that extended from his left cheek to his left forehead and auricle. He felt a brief stabbing pain when his face was touched in the territory of the first and second divisions of the left trigeminal nerve. There were no other neurological signs. Magnetic resonance imaging (MRI) of the brain 7 days after onset revealed dissection of the left intracranial vertebral artery without brain infarction. The pain gradually disappeared in approximately 6 weeks, and the patient remained asymptomatic thereafter, except for a brief episode of vertigo. Follow-up MRI revealed progressive narrowing of the artery without brain infarction. This case indicates that IVAD can present with isolated facial pain that mimics TN. IVAD should be considered in the differential diagnosis of acute facial pain or TN. PMID- 26146577 TI - Ureteral Injury with Delayed Massive Hematuria after Transvaginal Ultrasound Guided Oocyte Retrieval. AB - We report a case of ureteral injury with delayed hematuria after transvaginal oocyte retrieval. A 28-year-old infertile patient with a history of previous laparoscopic resection of endometriotic nodes of both sacrouterine ligaments presented with abdominal pain one day after oocyte retrieval. Four days after oocyte retrieval, she presented with massive hematuria that reappeared 6 days after oocyte retrieval. Monopolar coagulation with wire electrode and insertion of a double-J-stent was performed during operative cystoscopy. The patient recovered completely after transfusion and had no signs of renal impairment after ureteric stent removal. This is the first report of ureteral injury after oocyte retrieval presenting itself with delayed massive hematuria and no signs of renal dysfunction or urinary leakage into retroperitoneal space. PMID- 26146578 TI - Management of Second Trimester Fetal Demise in a Noncommunicating Uterine Horn. AB - Mullerian anomalies are uncommon but when present they can increase the risk of obstetrical complications. Anomalies such as bicornuate and unicornuate uterus can also increase the surgical risks of pregnancy termination. The diagnostic approach and surgical management must be individualized for each patient so that the termination procedure is safe and preserves fertility. We present a case of a patient with a 17-week pregnancy with fetal demise in a noncommunicating right uterine horn. Laparotomy and hysterotomy were required for evacuation of the fetus. The use of appropriate imaging studies to diagnose suspected uterine anomalies and a flexible and individualized operative strategy are essential for reducing complications associated with the termination of abnormal or unintended pregnancies in women with Mullerian anomalies. PMID- 26146579 TI - External Iliac Artery-Appendicular Fistula due to Antegrade Unusual Migration of K-Wire from Hip to Pelvis: An Unreported Complication. AB - Background. K-wires are thought to be extremely safe implants and complications as a result of direct insertion or migration are very rare. Complications may be life-threatening in some instances where migration results in injury to vital organs. We report one such case where antegrade migration of K-wire from the hip resulted in injury to external iliac artery and formation of external iliac artery-appendicular fistula. No such complication due to migration has ever been reported in the literature. Case Description. A 15-year-old boy presented with lower abdominal pain, right lower limb swelling and pain, inability to walk, and rectal bleeding for 1 month after 2 K-wires had been inserted in his right hip joint for treatment of slipped capital femoral epiphysis the previous year. On investigation, he was diagnosed to have external iliac artery-appendicular fistula for which he was surgically treated. Clinical Relevance. Antegrade migration of K-wire from hip joint may lead to life-threatening injuries which can be minimized by bending the end of the K-wire, keeping the tip protruding outside the skin wherever possible and by early removal of K-wire once its purpose has been achieved. PMID- 26146580 TI - Polyarticular Septic Arthritis in an Immunocompetent Adult: A Case Report and Review of the Literature. AB - Septic arthritis is a clinical emergency requiring prompt diagnosis and treatment to avoid significant morbidity and mortality. Polyarticular septic arthritis (PASA) accounts for 15% of all infectious arthritides and rarely occurs in immunocompetent adults. Staphylococcus aureus is the most commonly isolated organism, with infection primarily affecting knees, shoulders, elbows, and hips. The morbidity associated with PASA is very high, and mortality in treated cases of PASA may be as high as 50% of cases. We report a case of PASA with associated epidural abscess in a healthy adult male, who presented with complaints of arthralgia and limited range of motion of his left shoulder, wrist, and ankle. He also presented with low back pain and motor weakness associated with an epidural abscess spanning L2-S1, with multilevel vertebral osteomyelitis. Surgical washout of the affected joints as well as decompressive laminectomies was performed, and he received a standard course of intravenous antibiotics. Staphylococcus aureus was isolated from joint aspirations and from blood cultures. The patient had a full neurological and functional recovery postoperatively with no sequelae. To the best of our knowledge this is the only case report of Staphylococcus aureus PASA with concomitant epidural abscess in an immunocompetent adult. PMID- 26146581 TI - Endoscopic Modified Medial Maxillectomy for Resection of an Inverted Papilloma Originating from the Entire Circumference of the Maxillary Sinus. AB - For treatment of a sinonasal inverted papilloma (IP), it is essential to have a definite diagnosis, to identify its origin by computed tomography (CT) and magnetic resonance imaging (MRI), and to select the appropriate surgical approach based on the staging system proposed by Krouse. Recently, a new surgical approach named endoscopic modified medial maxillectomy (EMMM) was proposed. This approach can preserve the inferior turbinate and nasolacrimal duct. We successfully treated sinonasal IP with EMMM in a 71-year-old female patient. In this patient, the sinonasal IP originated from the entire circumference of the maxillary sinus. EMMM is not a difficult procedure and provides good visibility of the operative field. Lacrimation and empty nose syndrome do not occur postoperatively as the nasolacrimal duct and inferior turbinate are preserved. EMMM is considered to be a very favorable approach for treatment of sinonasal IP. PMID- 26146582 TI - Successful Treatment of Candida parapsilosis Fungemia in Two Preterms with Voriconazole. AB - Herein, we report two preterms with invasive candidiasis refractory to liposomal amphotericin B (AMB) treatment in spite of low MIC levels (MIC: 0.5 mcg/mL). Both of the patients' blood cultures were persistently positive for C. parapsilosis despite high therapeutic doses (AMB: 7 mg/kg per day). After starting voriconazole blood cultures became negative and both of the patients were treated successfully without any side effects. In conclusion, although it is not a standard treatment in neonatal patients, our limited experience with these patients suggests that voriconazole appears to be a safe antifungal agent to be used in critically ill preterm infants with persistent fungemia despite AMB treatment. PMID- 26146583 TI - Megalourethra with Y-Type Duplication of Urethra Presented as Perianal Fistula: A Rare Case Report. AB - Megalourethra with Y-type duplication is an extremely rare anomaly. We report here one such case, diagnosed with retrograde urethrogram, which was done from both penile meatus and perianal opening simultaneously. Patient was successfully treated by laser optical internal urethrotomy (OIU), excision of duplicated urethra, and reduction urethroplasty in a single stage. PMID- 26146584 TI - The Youngest Korean Case of Urachal Carcinoma. AB - Urachal anomalies are relatively uncommon and result from incomplete obliteration of the urachus perinatally. In children, most urachal diseases including urachal cysts and sinuses are benign, and these can sometimes become secondarily infected. Malignant involvement of the urachus is rarely reported, one in 5 million people, accounting for 0.35% to 0.7% of all bladder cancers. There are only five cases of urachal cancer diagnosed at the age of twenties in English written literature. Age at the diagnosis of urachal carcinoma is important to understand pathogenetic transition from benign to malignancy. A 26-year-old man visited our clinic with gross hematuria starting a few months before. CT scan showed a 4.0 * 6.8 cm sized lobulated cystic mass over the bladder dome. Cystoscopy showed a ball-shaped extrinsic mass from the bladder dome with intact bladder mucosa. With an impression of urachal cancer, laparoscopic partial cystectomy with wide excision of urachus was performed. Final diagnosis was well differentiated mucinous urachal adenocarcinoma invading bladder muscle, staged as pT3a based on Sheldon's staging system. To our best knowledge, this case is the youngest Korean case of urachal carcinoma (the fourth youngest ever in English written literature). PMID- 26146585 TI - Content and Bioaccumulation of Nine Mineral Elements in Ten Mushroom Species of the Genus Boletus. AB - Concentrations and bioconcentration potential of nine elements (Ca, Cu, Fe, K, Mg, Mn, Na, P, and Zn) in ten species of wild edible Boletus and the corresponding underlying soils were analyzed. The analyses were performed using inductively coupled plasma atomic emission spectrophotometer. Boletus showed relative abundant contents of P, K, Fe, Mg, Ca, and Na and less of Zn, Cu, and Mn. Caps compared to stalks were enriched in P, K, Cu, Mg, and Zn, while stalks were enriched in Mn. The elements such as P and K were accumulated (BCF > 1), while Ca, Fe, Mg, Mn, and Na were excluded (BCF < 1) in the fruiting bodies. The correlation analysis indicated high correlations between Cu, Mn, Ca, and Fe in the mushrooms as compared to the corresponding soils. Significant correlations were also obtained between Cu-P (r = 0.775), Fe-P (r = 0.728), and Zn-P (r = 0.76) for caps and Cu-Mg (r = 0.721), Fe-Mg (r = 0.719), Zn-Mg (r = 0.824), and Zn-P (r = 0.818) for stalks. The results of this study imply that ability of fungi to accumulate elements from substrate could be influenced by mushroom species and underlying soil substrates. PMID- 26146586 TI - Ranking of Prokaryotic Genomes Based on Maximization of Sortedness of Gene Lengths. AB - How variations of gene lengths (some genes become longer than their predecessors, while other genes become shorter and the sizes of these factions are randomly different from organism to organism) depend on organismal evolution and adaptation is still an open question. We propose to rank the genomes according to lengths of their genes, and then find association between the genome rank and variousproperties, such as growth temperature, nucleotide composition, and pathogenicity. This approach reveals evolutionary driving factors. The main purpose of this study is to test effectiveness and robustness of several ranking methods. The selected method of evaluation is measuring of overall sortedness of the data. We have demonstrated that all considered methods give consistent results and Bubble Sort and Simulated Annealing achieve the highest sortedness. Also, Bubble Sort is considerably faster than the Simulated Annealing method. PMID- 26146589 TI - Visualising Geophylogenies in Web Maps Using GeoJSON. AB - This article describes a simple tool to display geophylogenies on web maps including Google Maps and OpenStreetMap. The tool reads a NEXUS format file that includes geographic information, and outputs a GeoJSON format file that can be displayed in a web map application. PMID- 26146588 TI - Catalytic Efficiency Is a Function of How Rhodium(I) (5 + 2) Catalysts Accommodate a Conserved Substrate Transition State Geometry: Induced Fit Model for Explaining Transition Metal Catalysis. AB - The origins of differential catalytic reactivities of four Rh(I) catalysts and their derivatives in the (5 + 2) cycloaddition reaction were elucidated using density functional theory. Computed free energy spans are in excellent agreement with known experimental rates. For every catalyst, the substrate geometries in the transition state remained constant (<0.1 A RMSD for atoms involved in bond making and -breaking processes). Catalytic efficiency is shown to be a function of how well the catalyst accommodates the substrate transition state geometry and electronics. This shows that the induced fit model for explaining biological catalysis may be relevant to transition metal catalysis. This could serve as a general model for understanding the origins of efficiencies of catalytic reactions. PMID- 26146587 TI - MicroRNAs: New Players in Anesthetic-Induced Developmental Neurotoxicity. AB - Growing evidence demonstrates that prolonged exposure to general anesthetics during brain development induces widespread neuronal cell death followed by long term memory and learning disabilities in animal models. These studies have raised serious concerns about the safety of anesthetic use in pregnant women and young children. However, the underlying mechanisms of anesthetic-induced neurotoxicity are complex and are not well understood. MicroRNAs are endogenous, small, non coding RNAs that have been implicated to play important roles in many different disease processes by negatively regulating target gene expression. A possible role for microRNAs in anesthetic-induced developmental neurotoxicity has recently been identified, suggesting that microRNA-based signaling might be a novel target for preventing the neurotoxicity. Here we provide an overview of anesthetic induced developmental neurotoxicity and focus on the role of microRNAs in the neurotoxicity observed in both human stem cell-derived neuron and animal models. Aberrant expression of some microRNAs has been shown to be involved in anesthetic induced developmental neurotoxicity, revealing the potential of microRNAs as therapeutic or preventive targets against the toxicity. PMID- 26146590 TI - A Simple Protein Precipitation-based Simultaneous Quantification of Lovastatin and Its Active Metabolite Lovastatin Acid in Human Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry using Polarity Switching. AB - Lovastatin is an anti-cholesterol lactone drug indicated for the treatment of hyperlipidemia and to reduce the risk of coronary heart disease. It is converted to the beta-hydroxy acid form (lovastatin acid) in vivo, which is the major pharmacologically active metabolite. Here, we describe the development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based method utilizing polarity switching for the simultaneous quantification of lovastatin and lovastatin acid in human plasma. Simple protein precipitation extraction and direct injection of the extracted samples without drying/reconstitution showed good recoveries of both analytes (~70%). The developed method exhibited satisfactory intra-day and inter-day accuracy and precision. The interconversion between lovastatin and lovastatin acid during sample preparation and storage was minimal (< 1.9%). The lower limits of quantification were 0.5 and 0.2 nM (or 0.2 and 0.084 ng/mL) for lovastatin and lovastatin acid, respectively, using only 50 MUL of plasma during extraction. The validated method was successfully applied to analyze plasma samples obtained from a healthy human subject who enrolled in a clinical drug interaction study involving lovastatin. PMID- 26146591 TI - Proteomic analysis of HEK293 cells expressing non small cell lung carcinoma associated epidermal growth factor receptor variants reveals induction of heat shock response. AB - In view of the fact that certain non small cell lung carcinoma associated epidermal growth factor receptor mutations keep the receptor constitutively active, the downstream effectors of altered activity of mutant receptors are largely unknown. By 2D gel electrophoresis and MALDI-TOF/MS analysis, we showed that increased activity of EGFR mutants, L858R, L861Q and A871G induce heat shock proteins such as Hsp70, Hsp60, Hsp90B1, Hsp5a, Hsp71 and few transcriptional factors. Of which, Hsp70 was observed to be regulated more selectively to L861Q mutant. Our results suggest the possible role of heat shock proteins in lung tumor progression considering EGFR mutations. PMID- 26146592 TI - Medical Histories: A Case Report of Pharmacovigilance in Supporting Dentists and Participation in a Drug-Safety Program. AB - INTRODUCTION: Antibiotics are a class of medications widely used by dentists. The class of agents has a number of listed side effects. This case report details an unusual adverse effect of tetracycline-induced psychosis recognized due to the diligence of a practitioner. To our knowledge, this is the first reported case by a dentist. CASE PRESENTATION: A 44-year-old patient was started on tetracycline therapy for prophylaxis before a periodontal procedure. The patient began having paranoid and psychotic experiences. The patient sought psychiatric medical care and was diagnosed with tetracycline-induced psychosis. He was treated with an antipsychotic drug, which resolved his symptoms. CONCLUSION: Dental medical histories are a resource that is underused and can often be of value in the continual assessment of drug safety and pharmacovigilance. PMID- 26146593 TI - Emerging Regenerative Approaches for Periodontal Reconstruction: Practical Applications From the AAP Regeneration Workshop. AB - FOCUSED CLINICAL QUESTION: Can emerging technologies for periodontal regeneration become clinical reality? SUMMARY: Emerging technologies are presenting options to hopefully improve the outcomes of regeneration in challenging clinical scenarios. Cellular allografts represent a current technology in which cells and scaffolds are being delivered directly to the periodontal lesion. Recombinant human fibroblast growth factor 2 and teriparatide (parathyroid 1-34) have each been tested in controlled prospective human randomized clinical trials, and both have been shown to have potential for periodontal regeneration. These examples, as well as other emerging technologies, show promise for continued advancement in the field of periodontal regenerative therapy. CONCLUSIONS: At present, there are indications that emerging technologies can be used successfully for periodontal regeneration. Case reports and clinical trials are being conducted with a variety of emerging technologies. However, many are yet to be approved by a regulatory agency, or there is a lack of evidence-based literature to validate their expanded use. PMID- 26146594 TI - Molecular Dynamics Simulations of DOPC Lipid Bilayers: The Effect of Lennard Jones Parameters of Hydrocarbon Chains. AB - The current Chemistry at Harvard Molecular Mechanics (CHARMM) force field cannot accurately describe the properties of unsaturated phospholipid membranes. In this paper, a series of simulations was performed in which the Lennard-Jones (L-J) parameters of lipid acyl chains of dioleoylphosphatidylcholine (DOPC) were systematically adjusted. The results showed that adjustment of the L-J parameters in lipid acyl chains can significantly improve the current CHARMM force field. It was found that the L-J parameters have different influences on the order parameters of the top half and bottom half of the chain, separated by the cis double bond. The order parameters of the top half and the bottom half of the chain are related to the area/lipid and the length of the chain, respectively. PMID- 26146595 TI - Modeling Disorders of Blood Coagulation in the Zebrafish. AB - Hemostasis, the process of blood clot formation and resolution in response to vascular injury, and thrombosis, the dysregulation of hemostasis leading to pathological clot formation, are widely studied. However, the genetic variability in hemostatic and thrombotic disorders is incompletely understood, suggesting that novel mediators have yet to be uncovered. The zebrafish is developing into a powerful in vivo model to study hemostasis, and its features as a model organism are well suited to (a) develop high-throughput screens to identify novel mediators of hemostasis and thrombosis, (b) validate candidate genes identified in human populations, and (c) characterize the structure/function relationship of gene products. In this review, we discuss conservation of the zebrafish hemostatic system, highlight areas for future study, and outline the utility of this model to study blood coagulation and its dysregulation. PMID- 26146597 TI - Pragmatic and Ethical Challenges of Incorporating the Genome into the Electronic Medical Record. AB - Recent successes in the use of gene sequencing for patient care highlight the potential of genomic medicine. For genomics to become a part of usual care, pertinent elements of a patient's genomic test must be communicated to the most appropriate care providers. Electronic medical records may serve as a useful tool for storing and disseminating genomic data. Yet, the structure of existing EMRs and the nature of genomic data pose a number of pragmatic and ethical challenges in their integration. Through a review of the recent genome-EMR integration literature, we explore concrete examples of these challenges, categorized under four key questions: What data will we store? How will we store it? How will we use it? How will we protect it? We conclude that genome-EMR integration requires a rigorous, multi-faceted and interdisciplinary approach of study. Problems facing the field are numerous, but few are intractable. PMID- 26146596 TI - Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses. AB - Craniosynostosis, a condition that includes the premature fusion of one or multiple cranial sutures, is a relatively common birth defect in humans and the second most common craniofacial anomaly after orofacial clefts. There is a significant clinical variation among different sutural synostoses as well as significant variation within any given single-suture synostosis. Craniosynostosis can be isolated (i.e., nonsyndromic) or occurs as part of a genetic syndrome (e.g., Crouzon, Pfeiffer, Apert, Muenke, and Saethre-Chotzen syndromes). Approximately 85 % of all cases of craniosynostosis are nonsyndromic. Several recent genomic discoveries are elucidating the genetic basis for nonsyndromic cases and implicate the newly identified genes in signaling pathways previously found in syndromic craniosynostosis. Published epidemiologic and phenotypic studies clearly demonstrate that nonsyndromic craniosynostosis is a complex and heterogeneous condition supporting a strong genetic component accompanied by environmental factors that contribute to the pathogenetic network of this birth defect. Large population, rather than single-clinic or hospital-based studies is required with phenotypically homogeneous subsets of patients to further understand the complex genetic, maternal, environmental, and stochastic factors contributing to nonsyndromic craniosynostosis. Learning about these variables is a key in formulating the basis of multidisciplinary and lifelong care for patients with these conditions. PMID- 26146598 TI - Phenome-Wide Association Studies: Leveraging Comprehensive Phenotypic and Genotypic Data for Discovery. AB - With the large volume of clinical and epidemiological data being collected, increasingly linked to extensive genotypic data, coupled with expanding high performance computational resources, there are considerable opportunities for comprehensively exploring the networks of connections that exist between the phenome and the genome. These networks can be identified through Phenome-Wide Association Studies (PheWAS) where the association between a collection of genetic variants, or in some cases a particular clinical lab variable, and a wide and diverse range of phenotypes, diagnoses, traits, and/or outcomes are evaluated. This is a departure from the more familiar genome-wide association study (GWAS) approach, which has been used to identify single nucleotide polymorphisms (SNPs) associated with one outcome or a very limited phenotypic domain. In addition to highlighting novel connections between multiple phenotypes and elucidating more of the phenotype-genotype landscape, PheWAS can generate new hypotheses for further exploration, and can also be used to narrow the search space for research using comprehensive data collections. The complex results of PheWAS also have the potential for uncovering new mechanistic insights. We review here how the PheWAS approach has been used with data from epidemiological studies, clinical trials, and de-identified electronic health record data. We also review methodologies for the analyses underlying PheWAS, and emerging methods developed for evaluating the comprehensive results of PheWAS including genotype-phenotype networks. This review also highlights PheWAS as an important tool for identifying new biomarkers, elucidating the genetic architecture of complex traits, and uncovering pleiotropy. There are many directions and new methodologies for the future of PheWAS analyses, from the phenotypic data to the genetic data, and herein we also discuss some of these important future PheWAS developments. PMID- 26146599 TI - Identification of Best Practices for Resident Aesthetic Clinics in Plastic Surgery Training: The ACAPS National Survey. AB - INTRODUCTION: Resident aesthetic clinics (RACs) have demonstrated good outcomes and acceptable patient satisfaction, but few studies have evaluated their educational, financial, or medicolegal components. We sought to determine RAC best practices. METHODS: We surveyed American Council of Academic Plastic Surgeon members (n = 399), focusing on operational details, resident supervision, patient safety, medicolegal history, financial viability, and research opportunities. Of the 96 respondents, 63 reported having a RAC, and 56% of plastic surgery residency program directors responded. RESULTS: RACs averaged 243 patient encounters and 53.9 procedures annually, having been in existence for 19.6 years (mean). Full-time faculty (73%) supervised chief residents (84%) in all aspects of care (65%). Of the 63 RACs, 45 were accredited, 40 had licensed procedural suites, 28 had inclusion/exclusion criteria, and 31 used anesthesiologists. Seventeen had overnight capability, and 17 had a Life Safety Plan. No cases of malignant hyperthermia occurred, but 1 facility death was reported. Sixteen RACs had been involved in a lawsuit, and 33 respondents reported financial viability of the RACs. Net revenue was transferred to both the residents' educational fund (41%) and divisional/departmental overhead (37%). Quality measures included case logs (78%), morbidity/mortality conference (62%), resident surveys (52%), and patient satisfaction scores (46%). Of 63 respondents, 14 have presented or published RAC-specific research; 80 of 96 of those who were surveyed believed RACs enhanced education. CONCLUSIONS: RACs are an important component of plastic surgery education. Most clinics are financially viable but carry high malpractice risk and consume significant resources. Best practices, to maximize patient safety and optimize resident education, include use of accredited procedural rooms and direct faculty supervision of all components of care. PMID- 26146600 TI - Characterization of a gold coated cantilever surface for biosensing applications. AB - Cantilever based sensors are a promising tool for a very diverse spectrum of biological sensors. They have been used for the detection of proteins, DNA, antigens, bacteria viruses and many other biologically relevant targets. Although cantilever sensing has been described for over 20 years, there are still no viable commercial cantilever-based sensing products on the market. Several reasons can be found for this - a lack of detailed understanding of the origin of signals being an important one. As a consequence application-relevant issues such as shelf life and robust protocols distinguishing targets from false responses have received very little attention. Here, we will discuss a cantilever sensing platform combined with an electrochemical system. The detected surface stress signal is modulated by applying a square wave potential to a gold coated cantilever. The square wave potential induces adsorption and desorption onto the gold electrode surface as well as possible structural changes of the target and probe molecules on the cantilever surface resulting in a measurable surface stress change. What sets this approach apart from regular cantilever sensing is that the quantification and identification of observed signals due to target probe interactions are not only a function of stress value (i.e. amplitude), but also of the temporal evolution of the stress response as a function of the rate and magnitude of the applied potential change, and the limits of the potential change. This paper will discuss three issues that play an important role in future successful applications of cantilever-based sensing. First, we will discuss what is required to achieve a large surface stress signal to improve sensitivity. Second, a mechanism to achieve an optimal probe density is described that improves the signal-to-noise ratio and response times of the sensor. Lastly, lifetime and long term measurements are discussed. PMID- 26146483 TI - Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at [Formula: see text][Formula: see text]. AB - The inclusive jet cross section for proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] was measured by the CMS Collaboration at the LHC with data corresponding to an integrated luminosity of 5.0[Formula: see text]. The measurement covers a phase space up to 2[Formula: see text] in jet transverse momentum and 2.5 in absolute jet rapidity. The statistical precision of these data leads to stringent constraints on the parton distribution functions of the proton. The data provide important input for the gluon density at high fractions of the proton momentum and for the strong coupling constant at large energy scales. Using predictions from perturbative quantum chromodynamics at next-to leading order, complemented with electroweak corrections, the constraining power of these data is investigated and the strong coupling constant at the Z boson mass [Formula: see text] is determined to be [Formula: see text], which is in agreement with the world average. PMID- 26146601 TI - Relationship Between Family Economic Resources, Psychosocial Well-being, and Educational Preferences of AIDS-Orphaned Children in Southern Uganda: Baseline Findings. AB - This study examines the relationship between economic resources, psychosocial well-being, and educational preferences of AIDS-orphaned children in southern Uganda. We use baseline data from a sample of 1410 AIDS-orphaned children (defined as children who have lost one or both biological parents to AIDS) enrolled in the Bridges to the Future study, a National Institute of Child Health and Human Development (NICHD) funded study. Analyses from both bivariate and multiple regression analyses indicate the following: 1) despite the well documented economic and psychosocial challenges AIDS-orphaned children face, many of these children have high educational plans and aspirations; 2) educational aspirations differ by orphanhood status (double orphan vs. single orphan); 3) regardless of orphanhood status, children report similar levels of psychosocial well-being; 4) high levels of family cohesion, positive perceptions of the future, school satisfaction, and lower levels of hopelessness (hopefulness) are associated with high educational aspirations; and 5) reported family economic resources at baseline, all seem to play a role in predicting children's educational preferences and psychosocial well-being. These findings suggest that the focus for care and support of orphaned children should not be limited to addressing their psychosocial needs. Addressing the economic needs of the households in which orphaned children live is equally important. Indeed, in the context of extreme poverty-in which most of the children represented in this study live-addressing structural factors, including poverty, may be a key driver in addressing their psychosocial functioning. PMID- 26146602 TI - Guideline contact dermatitis: S1-Guidelines of the German Contact Allergy Group (DKG) of the German Dermatology Society (DDG), the Information Network of Dermatological Clinics (IVDK), the German Society for Allergology and Clinical Immunology (DGAKI), the Working Group for Occupational and Environmental Dermatology (ABD) of the DDG, the Medical Association of German Allergologists (AeDA), the Professional Association of German Dermatologists (BVDD) and the DDG. PMID- 26146604 TI - The Mysteries of Streptococcal Pharyngitis. PMID- 26146603 TI - Cockroach, tick, storage mite and other arthropod allergies: Where do we stand with molecular allergy diagnostics?: Part 15 of the Series Molecular Allergology. PMID- 26146606 TI - Molecular backgrounds of ERAP1 downregulation in cervical carcinoma. AB - The antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of the APM component ERAP1 is associated with progression and poor clinical outcome in cervical carcinoma. However, the underlying mechanisms of ERAP1 protein downregulation remain to be established. We investigated ERAP1 mRNA expression levels in 14 patients with established ERAP1 protein downregulation. To further examine the possible pretranscriptional mechanisms of ERAP1 downregulation, ERAP1 DNA mutation status was analyzed alongside existing data on various single nucleotide polymorphisms. Moreover, loss of heterozygosity at various loci in the ERAP1 gene was investigated. In cases with ERAP1 protein downregulation, ERAP1 mRNA quantities were found to be significantly lower than in a cohort with normal ERAP1 protein expression (P = 0.001). Loss of heterozygosity was demonstrated to occur in up to 50% of tumors with ERAP1 downregulation. Our data indicate that ERAP1 downregulation is associated with loss of heterozygosity. These data provide the first insight into in vivo mechanisms of ERAP1 downregulation in cervical carcinoma. PMID- 26146608 TI - Attention-Deficit/Hyperactivity Disorder, Autistic Traits, and Substance Use Among Missouri Adolescents. AB - BACKGROUND: Although existing literature demonstrates the association of attention-deficit/hyperactivity disorder (ADHD) with both substance use (SU) and autism spectrum disorder (ASD), few studies have examined rates of SU among adolescents with elevated ASD symptoms, with or without comorbid ADHD. Clinic based studies suggest a possible protective effect of ASD against SU, but this has not been confirmed in population-based studies. OBJECTIVE: We examined alcohol, tobacco, and drug use in adolescents with either ADHD, elevated autistic traits, or both as compared with controls. METHODS: Subjects (N = 2937) who were 13 to 17 years old from a Missouri population-based large sibship sample were assessed for ADHD, autistic traits, and SU with the use of parent-report questionnaires. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD symptom criterion (Criterion A) was applied to the Strengths and Weaknesses of ADHD-symptoms and Normal-behavior (SWAN) questionnaire item responses to determine ADHD diagnosis. The presence of elevated autistic traits was defined as a raw Social Responsiveness Scale (SRS) score of 62 (95th percentile for this sample) or higher. SU was determined with the use of three items from the Child Behavior Checklist (CBCL). Statistical methods used included logistic and fractional polynomial regression. RESULTS: As compared with controls, adolescents with ADHD were at increased risk for alcohol, tobacco, and drug use whether or not they had elevated autistic traits. Adolescents with elevated autistic traits were at significantly increased risk for drug use other than alcohol and tobacco, even if they did not have ADHD. Among those with raw SRS scores in the range of about 20 (normal) to 80 (consistent with mild to moderate ASD), adolescents with ADHD had higher levels of SU than control individuals with similar levels of autistic traits. However, strong conclusions cannot be drawn regarding individuals with very low or very high SRS scores as a result of sparse data. CONCLUSIONS: This study confirms previous research showing an increased risk of SU among adolescents with ADHD. It also provides new information indicating that adolescents with high levels of autistic traits are at elevated risk for alcohol and tobacco use if they have comorbid ADHD; in addition, they may be at high risk for other drug use, even if they do not have comorbid ADHD. Therefore, it should not be assumed that adolescents with mild to moderate ASD have a low risk of SU, especially if ADHD is also present. PMID- 26146605 TI - Regenerating Retinal Pigment Epithelial Cells to Cure Blindness: A Road Towards Personalized Artificial Tissue. AB - Retinal pigment epithelium (RPE) is a polarized monolayer tissue that functions to support the health and integrity of retinal photoreceptors (PRs). RPE atrophy has been linked to pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness in elderly in the USA. RPE atrophy in AMD leads to the PR cell death and vision loss. It is thought that replacing diseased RPE with healthy RPE tissue can prevent PR cell death. Retinal surgical innovations have provided proof-of-principle data that autologous RPE tissue can replace diseased macular RPE and provide visual rescue in AMD patients. Current efforts are focused on developing an in vitro tissue using natural and synthetic scaffolds to generate a polarized functional RPE monolayer. In the future, these tissue engineering approaches combined with pluripotent stem cell technology will lead to the development of personalized and "off-the-shelf" cell therapies for AMD patients. This review summarizes the historical development and ongoing efforts in surgical and in vitro tissue engineering techniques to develop a three dimensional therapeutic native RPE tissue substitute. PMID- 26146607 TI - An improved understanding of cancer genomics through massively parallel sequencing. AB - DNA sequencing technology advances have enabled genetic investigation of more samples in a shorter time than has previously been possible. Furthermore, the ability to analyze and understand large sequencing datasets has improved due to concurrent advances in sequence data analysis methods and software tools. Constant improvements to both technology and analytic approaches in this fast moving field are evidenced by many recent publications of computational methods, as well as biological results linking genetic events to human disease. Cancer in particular has been the subject of intense investigation, owing to the genetic underpinnings of this complex collection of diseases. New massively-parallel sequencing (MPS) technologies have enabled the investigation of thousands of samples, divided across tens of different tumor types, resulting in new driver gene identification, mutagenic pattern characterization, and other newly uncovered features of tumor biology. This review will focus both on methods and recent results: current analytical approaches to DNA and RNA sequencing will be presented followed by a review of recent pan-cancer sequencing studies. This overview of methods and results will not only highlight the recent advances in cancer genomics, but also the methods and tools used to accomplish these advancements in a constantly and rapidly improving field. PMID- 26146609 TI - Cymene and Metformin treatment effect on biochemical parameters of male NMRI mice fed with high fat diet. AB - BACKGROUND: The increasing prevalence of obesity is considered a serious global health threat. Mainly due to change of diet and reduced physical activity, obesity is an important risk factor for chronic diseases. A higher level of cytokines and a general inflammatory state has also been associated with this condition. With this regard, potential anti-obesity compounds with anti inflammatory properties could be beneficial in better control of the disease. p Cymene is a natural aromatic compound that has been shown to have anti inflammatory properties, while the antidiabetic drug metformin has been observed to be effective as an aid for weight loss. In this study, the effect of these comounds was compared in a high fat diet treated mice model. METHODS: 48 adult NMRI mice were randomly divided into six groups: control group receiving a normal diet, high fat diet (HFD) fed control group, sham group receiving HFD and sunflower seed oil, Experimental group1 (E1) receiving HFD and 20 mg/kg metformin, Experimental group2 (E2) receiving 20 mg/kg metformin and 20 mg/kg p cymene, Experimental group3 (E3) receiving 20 mg/kg p-cymene. Compounds were administered by intragastric gavage for 45 days. RESULTS: Non-fasting glucose serum levels, ALT, and ALP of E2 and E3 decreased significantly compared to HFD control group. In the E3 group, AST levels decrease was also significant. In E1, non-fasting glucose and TG serum levels decreased significantly compared to HFD control group. Histological observations on liver tissue showed an increase of lipid droplets in the HFD control group compared with the normal group, while upon treatment with the compounds, lipid droplets decreased and the cells appeared to be more ordered. CONCLUSION: p-Cymene has a potential to ameliorate biochemical parameters in high fat diet treated mice, and its concurrent use with metformin was effective. PMID- 26146610 TI - Dementia Prevention: optimizing the use of observational data for personal, clinical, and public health decision-making. AB - Worldwide, over 35 million people suffer from Alzheimer's disease and related dementias. This number is expected to triple over the next 40 years. How can we improve the evidence supporting strategies to reduce the rate of dementia in future generations? The risk of dementia is likely influenced by modifiable factors such as exercise, cognitive activity, and the clinical management of diabetes and hypertension. However, the quality of evidence is limited and it remains unclear whether specific interventions to reduce these modifiable risk factors can, in turn, reduce the risk of dementia. Although randomized controlled trials are the gold-standard for causality, the majority of evidence for long term dementia prevention derives from, and will likely continue to derive from, observational studies. Although observational research has some unavoidable limitations, its utility for dementia prevention might be improved by, for example, better distinction between confirmatory and exploratory research, higher reporting standards, investment in effectiveness research enabled by increased data-pooling, and standardized exposure and outcome measures. Informed decision making by the general public on low-risk health choices that could have broad potential benefits could be enabled by internet-based tools and decision-aids to communicate the evidence, its quality, and the estimated magnitude of effect. PMID- 26146611 TI - In Sync: The Effect of Physiology Feedback on the Match between Heart Rate and Self-Reported Stress. AB - Over the past years self-tracking of physiological parameters has become increasingly common: more and more people are keeping track of aspects of their physiological state (e.g., heart rate, blood sugar, and blood pressure). To shed light on the possible effects of self-tracking of physiology, a study was conducted to test whether physiology feedback has acute effects on self-reported stress and the extent to which self-reported stress corresponds to physiological stress. In this study, participants executed several short tasks, while they were either shown visual feedback about their heart rate or not. Results show that self-reported stress is more in sync with heart rate for participants who received physiology feedback. Interactions between two personality factors (neuroticism and anxiety sensitivity) and feedback on the level of self-reported stress were found, indicating that while physiology feedback may be beneficial for individuals high in neuroticism, it may be detrimental for those high in anxiety sensitivity. Additional work is needed to establish how the results of this study may extend beyond immediate effects in a controlled lab setting, but our results do provide a first indication of how self-tracking of physiology may lead to better body awareness and how personality characteristics can help us predict which individuals are most likely to benefit from self-tracking of physiology. PMID- 26146613 TI - Dental Stem Cell Migration on Pulp Ceiling Cavities Filled with MTA, Dentin Chips, or Bio-Oss. AB - MTA, Bio-Oss, and dentin chips have been successfully used in endodontics. The aim of this study was to assess the adhesion and migration of dental stem cells on human pulp ceiling cavities filled with these endodontic materials in an experimental model, which mimics the clinical conditions of regenerative endodontics. Cavities were formed, by a homemade mold, on untouched third molars, filled with endodontic materials, and observed with electron microscopy. Cells were seeded on cavities' surface and their morphology and number were analysed. The phenomenon of tropism was assessed in a migration assay. All three materials demonstrated appropriate microstructures for cell attachment. Cells grew on all reagents, but they showed a differential morphology. Moreover, variations were observed when comparing cells numbers on cavity's filling versus the surrounding dentine disc. The highest number of cells was recorded on dentin chips whereas the opposite was true for Bio-Oss. This was confirmed in the migration assay where a statistically significant lower number of cells migrated towards Bio-Oss as compared to MTA and dentin chips. This study highlights that MTA and dentin chips have a greater potential compared to Bio-Oss regarding the attraction of dental stem cells and are good candidates for bioengineered pulp regeneration. PMID- 26146612 TI - The Role of Mast Cell Specific Chymases and Tryptases in Tumor Angiogenesis. AB - An association between mast cells and tumor angiogenesis is known to exist, but the exact role that mast cells play in this process is still unclear. It is thought that the mediators released by mast cells are important in neovascularization. However, it is not known how individual mediators are involved in this process. The major constituents of mast cell secretory granules are the mast cell specific proteases chymase, tryptase, and carboxypeptidase A3. Several previous studies aimed to understand the way in which specific mast cell granule constituents act to induce tumor angiogenesis. A body of evidence indicates that mast cell proteases are the pivotal players in inducing tumor angiogenesis. In this review, the likely mechanisms by which tryptase and chymase can act directly or indirectly to induce tumor angiogenesis are discussed. Finally, information presented here in this review indicates that mast cell proteases significantly influence angiogenesis thus affecting tumor growth and progression. This also suggests that these proteases could serve as novel therapeutic targets for the treatment of various types of cancer. PMID- 26146614 TI - The Role of Mifepristone in Meningiomas Management: A Systematic Review of the Literature. AB - OBJECTIVES: We performed a systematic literature review to analyze the clinical application and the safety of mifepristone, a prominent antiprogesterone agent, in meningioma patients. MATERIALS AND METHODS: A systematic search was performed through Medline, Cochrane, and clinicaltrials.gov databases from 1960 to 2014. Study Selection. Studies were selected through a PICO approach. Population was meningioma patients, meningioma cells cultures, and animal models. Intervention was mifepristone administration. Control was placebo administration or any other drug tested. Outcomes were clinical and radiological responsiveness, safety profile, and cell growth inhibition. RESULTS: A total of 7 preclinical and 6 clinical studies and one abstract were included. Encouraging results were found in preclinical studies. Concerning clinical studies, the response rate to mifepristone in terms of radiological regression and symptomatic improvement/stability in patients with inoperable meningioma was low. In meningiomatosis, favorable preliminary results were recorded. The safety profile was good. Limitations were as follows. The tumoral expression of progesterone receptors was not analyzed systematically in every study considered. CONCLUSIONS: No clear evidence exists to recommend mifepristone in inoperable meningiomas. Preliminary encouraging results were found in diffuse meningiomatosis. Mifepristone is a well-tolerated treatment. Patients' selection and hormonal profile analysis in meningiomas are fundamental for a better understanding of its benefit. Multicenter placebo-controlled trials are required. PMID- 26146615 TI - Anatomical, Physiological, and Molecular Imaging for Pancreatic Cancer: Current Clinical Use and Future Implications. AB - Pancreatic adenocarcinoma is one of the deadliest human malignancies. Early detection is difficult and effective treatment is limited. Verifying the presence of micrometastatic dissemination and vessel invasion remains elusive, limiting radiological staging once this diagnosis is made. Diagnostic imaging provides independent tools to evaluate and characterize the biologic behavior of pancreatic cancer. Conventional anatomic imaging alone with either CT or MRI yields useful information on organ involvement but is limited in providing molecular and physiological information. Molecular imaging techniques such as PET or MRS provide information on metabolic and signaling pathways. Advanced MR sequences that target physiological parameters expand imaging options to characterize these tumors. By considering the parametric data from these three imaging approaches (anatomic, molecular, and physiological) we can better define specific tumor signatures. Such parametric characterization can provide insight into tumor metabolism, cellular density, protein expression, focal perfusion, and vascular permeability of these tumors. Radiogenomics research has already demonstrated ability to obtain information about cancer's genotype and phenotype; this is without invasive procedures or surgery. Further advances in these areas of experimental imaging hold promise to enable future clinical advances in detection and therapy of pancreatic cancer. PMID- 26146617 TI - Erratum to "Radial Quantitative Ultrasound and Dual Energy X-Ray Absorptiometry: Intermethod Agreement for Bone Status Assessment in Children". PMID- 26146616 TI - OSM Enhances Angiogenesis and Improves Cardiac Function after Myocardial Infarction. AB - Oncostatin M (OSM) has been reported to stimulate angiogenesis by upregulating VEGF and bFGF, implying that it could be a therapeutic strategy in treating ischemic diseases. The present study was aimed at investigating whether OSM could improve cardiac function via prompting angiogenesis following myocardial infarction (MI). Wild type (WT) and Obeta knock-out (Obeta (-/-)) mice were, respectively, randomized into sham group, MI + vehicle group, and MI + OSM group. WT mice displayed significantly impaired cardiac function after MI. OSM treatment attenuated cardiac dysfunction in WT MI mice, while Obeta deletion abrogated the protective effects. Besides, OSM attenuated heart hypertrophy and pulmonary congestion evidenced by decreased heart weight/body weight and lung weight/body weight ratio. Further, reduction of apoptosis and fibrosis in infarct border zone was observed in OSM treated WT MI mice compared with vehicle. Moreover, in WT mice subjected to MI, OSM treatment significantly increased capillary density along with upregulation of p-Akt and angiogenic factors VEGF and bFGF in comparison with vehicle, and this phenomenon was not found in Obeta (-/-) mice. In conclusion, OSM treatment preserved cardiac function, inhibited apoptosis and fibrosis, and stimulated angiogenesis via upregulating VEGF and bFGF in infarct border zone of ischemic myocardium, indicating that OSM could be a novel therapeutic target for MI. PMID- 26146618 TI - The Meditative Mind: A Comprehensive Meta-Analysis of MRI Studies. AB - Over the past decade mind and body practices, such as yoga and meditation, have raised interest in different scientific fields; in particular, the physiological mechanisms underlying the beneficial effects observed in meditators have been investigated. Neuroimaging studies have studied the effects of meditation on brain structure and function and findings have helped clarify the biological underpinnings of the positive effects of meditation practice and the possible integration of this technique in standard therapy. The large amount of data collected thus far allows drawing some conclusions about the neural effects of meditation practice. In the present study we used activation likelihood estimation (ALE) analysis to make a coordinate-based meta-analysis of neuroimaging data on the effects of meditation on brain structure and function. Results indicate that meditation leads to activation in brain areas involved in processing self-relevant information, self-regulation, focused problem-solving, adaptive behavior, and interoception. Results also show that meditation practice induces functional and structural brain modifications in expert meditators, especially in areas involved in self-referential processes such as self-awareness and self-regulation. These results demonstrate that a biological substrate underlies the positive pervasive effect of meditation practice and suggest that meditation techniques could be adopted in clinical populations and to prevent disease. PMID- 26146619 TI - Multiwall Carbon Nanotube-Induced Apoptosis and Antioxidant Gene Expression in the Gills, Liver, and Intestine of Oryzias latipes. AB - Multiwall carbon nanotubes (MWCNTs) have many attractive properties with potential applications in various fields. Despite their usefulness, however, the associated waste can be hazardous to the environment. To examine adverse effects in aquatic environments, Oryzias latipes were exposed to MWCNTs dispersed in water for 14 days and apoptosis and antioxidant gene expression were observed. This work showed that in gills exposed to 100 mg/L MWCNTs for 4 days, there was significant p53, caspase-3 (Cas3), caspase-8 (Cas8), and caspase-9 (Cas9) gene expression relative to the controls, while catalase (CAT) and glutathione-S transferase (GST) expression were reduced. At 14 days, CAT, GST, and metallothionein (MT) were induced significantly in the gills and Cas3, Cas8, and Cas9 were induced in the liver. No significant gene induction was seen in intestine. Intracellular reactive oxygen species (ROS) were increased significantly only at 14 days. Histologically, no apoptosis was observed with exposure to 100 mg/L MWCNTs for 21 days. The gills were more sensitive to MWCNT toxicity than the other organs. Males had higher apoptosis gene induction than females. These results demonstrated that MWCNTs could cause apoptosis in a manner influenced by tissue and gender in aqueous environments. PMID- 26146620 TI - Species Identification and Clarithromycin Susceptibility Testing of 278 Clinical Nontuberculosis Mycobacteria Isolates. AB - Purpose of this paper is to analyze different species' proportion of nontuberculosis mycobacteria (NTM) and susceptibility to clarithromycin of different species. 278 clinical NTM isolates were identified into species by using 16S rRNA, rpoB and hsp65. Then clarithromycin susceptibility testing against different species was done separately, using microplate Alamar Blue assay. Finally, resistance isolates' erm(41) of M. abscessus were sequenced in order to analyze mechanisms for clarithromycin resistant. In this test, 131 isolates (47%) belonged to M. avium complex (MAC), and 70 isolates (25%) belonged to M. abscessus. Nearly all the M. abscessus subsp. abscessus resistant to clarithromycin had T28 in erm(41). However, all the M. abscessus subsp. abscessus susceptible to clarithromycin had C28 in erm(41). In this study, we find that MAC was the most common pathogens of NTM, and the second one was M. abscessus. However, M. chelonei, M. fuerth, and M. gordon were rare. Clarithromycin had a good inhibition activity against all the NTM species except M. abscessus subsp. abscessus. The erm(41) genotype is of high relevance to clarithromycin resistance. PMID- 26146621 TI - Epidemiology of Neonatal Sepsis and Implicated Pathogens: A Study from Egypt. AB - Prospective analytic study was conducted in NICUs of three Egyptian Neonatal Network (EGNN) participants in Mansoura Hospitals in Egypt over a period of 18 months from March 2011 to August 2012. By using EGNN 28-day discharge form, all demographic, clinical, and laboratory data were recorded and studied. During the study period, 357 neonates were diagnosed as suspected sepsis with an incidence of 45.9% (357/778) among the admitted neonates at the three neonatal intensive care units. 344 neonates (sex ratio = 1.3:1) were enrolled in the study in which 152 (44.2%) were classified as early onset sepsis EOS (<=72 hr) and 192 (55.8%) as late onset sepsis LOS (>72 hr). Among the LOS cases, 33.9% (65/192) were caused by nosocomial infections. In 40.7% (140/344), sepsis was confirmed by positive blood culture. The total mortality rate for the proven neonatal sepsis was 51% (25/49) and 42.9% (39/91) for EOS and LOS, respectively. Coagulase negative staphylococci were predominant isolates in both EOS and LOS, followed by Klebsiella pneumoniae. Most of the bacterial isolates had low sensitivity to the commonly used empiric antibiotics. However, 70.1% (89/127) exhibited multidrug resistance. Best sensitivities among Gram-positive isolates were found against imipenem, ciprofloxacin, vancomycin, and amikacin. PMID- 26146623 TI - Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production. AB - Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L(-1) myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L(-1) myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway) due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that "there is a there there" for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality. PMID- 26146624 TI - Environmental Stability and Residual Stresses in Zirconia Femoral Head for Total Hip Arthroplasty: In Vitro Aging versus Retrieval Studies. AB - The objective of this study was to compare the low temperature degradation (LTD) behavior of femoral heads made of 3Y-TZP as observed on retrievals with that induced in vitro upon prolonged exposures to a hydrothermal environment. The time dependent evolution of tetragonal-to-monoclinic transformation and the related residual stresses were nondestructively monitored by Raman microspectroscopy. An increasing intensification of tensile and compressive stresses was detected with increasing hydrothermal aging duration in tetragonal and monoclinic phases, respectively. The dependence of monoclinic fraction upon exposure time was rationalized through the Mehl-Avrami-Johnson (MAJ) formalism in order to interpret the LTD process according to a two-step mechanism of formation and growth of monoclinic nuclei. In vitro results were compared to in vivo monoclinic contents in the same type of 3Y-TZP head retrievals after implantation periods of 1.6-16.6 y, also including literature data previously reported by other authors. One-hour exposure under the selected aging condition is estimated to correspond to in vivo exposures of 4 and 2 years according to ISO and ASTM criteria, respectively. A critical review of these two criteria according to the present analyses revealed that the ASTM simulation predicts more closely the in vivo results as compared to the ISO one. PMID- 26146622 TI - Hypoxia-Inducible Factor-1 in Physiological and Pathophysiological Angiogenesis: Applications and Therapies. AB - The cardiovascular system ensures the delivery of oxygen and nutrients to all cells, tissues, and organs. Under extended exposure to reduced oxygen levels, cells are able to survive through the transcriptional activation of a series of genes that participate in angiogenesis, glucose metabolism, and cell proliferation. The oxygen-sensitive transcriptional activator HIF-1 (hypoxia inducible factor-1) is a key transcriptional mediator of the response to hypoxic conditions. The HIF-1 pathway was found to be a master regulator of angiogenesis. Whether the process is physiological or pathological, HIF-1 seems to participate in vasculature formation by synergistic correlations with other proangiogenic factors such as VEGF (vascular endothelial growth factor), PlGF (placental growth factor), or angiopoietins. Considering the important contributions of HIF-1 in angiogenesis and vasculogenesis, it should be considered a promising target for treating ischaemic diseases or cancer. In this review, we discuss the roles of HIF-1 in both physiological/pathophysiological angiogenesis and potential strategies for clinical therapy. PMID- 26146625 TI - Can Early Rehabilitation after Total Hip Arthroplasty Reduce Its Major Complications and Medical Expenses? Report from a Nationally Representative Cohort. AB - OBJECTIVE: To investigate whether early rehabilitation reduces the occurrence of posttotal hip arthroplasty (THA) complications, adverse events, and medical expenses within one postoperative year. METHOD: We retrospectively retrieve data from Taiwan's National Health Insurance Research Database. Patients who had undergone THA during the period from 1998 to 2010 were recruited, matched for propensity scores, and divided into 2 groups: early rehabilitation (Early Rehab) and delayed rehabilitation (Delayed Rehab). RESULTS: Eight hundred twenty of 999 THA patients given early rehabilitation treatments were matched to 205 of 233 THA patients given delayed rehabilitation treatments. The Delayed Rehab group had significantly (all p < 0.001) higher medical and rehabilitation expenses and more outpatient department (OPD) visits than the Early Rehab group. In addition, the Delayed Rehab group was associated with more prosthetic infection (odds ratio (OR): 3.152; 95% confidence interval (CI): 1.211-8.203; p < 0.05) than the Early Rehab group. CONCLUSIONS: Early rehabilitation can significantly reduce the incidence of prosthetic infection, total rehabilitation expense, total medical expenses, and number of OPD visits within the first year after THA. PMID- 26146626 TI - Production of Human Endothelial Cells Free from Soluble Xenogeneic Antigens for Bioartificial Small Diameter Vascular Graft Endothelization. AB - Arterial bypass graft implantation remains the primary therapy for patients with advanced cardiovascular disease, but most lack adequate saphenous vein or other conduits for bypass procedures and would benefit from a bioartificial conduit. This study aimed to produce human endothelial cells (hECs) in large scale, free from xenogeneic antigens, to develop a small diameter, compatible vessel for potential use as a vascular graft. Human adipose-derived stromal cells (hASCs) were isolated, cultured, and differentiated in the presence of human serum and used for the reendothelization of a decellularized rat aorta. hASC derived ECs (hASC-ECs) expressed VEGFR2, vWf and CD31 endothelial cell markers, the latter in higher levels than hASCs and HUVECs, and were shown to be functional. Decellularization protocol yielded aortas devoid of cell nuclei, with preserved structure, including a preserved basement membrane. When seeded with hASC-ECs, the decellularized aorta was completely reendothelized, and the hASC-ECs maintained their phenotype in this new condition. hASCs can be differentiated into functional hECs without the use of animal supplements and are capable of reendothelizing a decellularized rat aorta while maintaining their phenotype. The preservation of the basement membrane following decellularization supported the complete reendothelization of the scaffold with no cell migration towards other layers. This approach is potentially useful for rapid obtention of compatible, xenogeneic-free conduit. PMID- 26146627 TI - Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms. AB - Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti inflammatory drugs (NSAIDs) have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception. PMID- 26146628 TI - Activation of Cell Surface Bound 20S Proteasome Inhibits Vascular Cell Growth and Arteriogenesis. AB - Arteriogenesis is an inflammatory process associated with rapid cellular changes involving vascular resident endothelial progenitor cells (VR-EPCs). Extracellular cell surface bound 20S proteasome has been implicated to play an important role in inflammatory processes. In our search for antigens initially regulated during collateral growth mAb CTA 157-2 was generated against membrane fractions of growing collateral vessels. CTA 157-2 stained endothelium of growing collateral vessels and the cell surface of VR-EPCs. CTA 157-2 bound a protein complex (760 kDa) that was identified as 26 kDa alpha7 and 21 kDa beta3 subunit of 20S proteasome in mass spectrometry. Furthermore we demonstrated specific staining of 20S proteasome after immunoprecipitation of VR-EPC membrane extract with CTA 157 2 sepharose beads. Functionally, CTA 157-2 enhanced concentration dependently AMC (7-amino-4-methylcoumarin) cleavage from LLVY (N-Succinyl-Leu-Leu-Val-Tyr) by recombinant 20S proteasome as well as proteasomal activity in VR-EPC extracts. Proliferation of VR-EPCs (BrdU incorporation) was reduced by CTA 157-2. Infusion of the antibody into the collateral circulation reduced number of collateral arteries, collateral proliferation, and collateral conductance in vivo. In conclusion our results indicate that extracellular cell surface bound 20S proteasome influences VR-EPC function in vitro and collateral growth in vivo. PMID- 26146629 TI - The Influence of Buddhist Meditation Traditions on the Autonomic System and Attention. AB - Cognitive and neuroscience research from the past several years has shed new light on the influences that meditative traditions have on the meditation practice. Here we review new evidence that shows that types of meditation that developed out of certain traditions such as Vajrayana and Hindu Tantric lead to heightened sympathetic activation and phasic alertness, while types of meditation from other traditions such as Theravada and Mahayana elicit heightened parasympathetic activity and tonic alertness. Such findings validate Buddhist scriptural descriptions of heightened arousal during Vajrayana practices and a calm and alert state of mind during Theravada and Mahayana types of meditation and demonstrate the importance of the cultural and philosophical context out of which the meditation practices develop. PMID- 26146631 TI - Male Partners' Involvement in the Prevention of Mother-to-Child Transmission of HIV and Associated Factors in Arba Minch Town and Arba Minch Zuria Woreda, Southern Ethiopia. AB - Background. Male involvement is an important determinant of prevention of mother to-child transmission of HIV. However, male involvement in prevention of mother to-child transmission of HIV in Ethiopia is not well known. Objectives. To assess male partners involvement in prevention of mother-to-child transmission of HIV and associated factors in Arba Minch town and Arba Minch Zuria woreda. Methods. Community based study was conducted in Arba Minch town and Arba Minch Zuria district. Multistage sampling technique was used and data were collected using interviewer administered standard questionnaire. Multiple logistic regression analysis was used to determine the presence of statistically significant associations between the outcome variable and the independent variables. Results. The level of male involvement in PMTCT program in Arba Minch town and Zuria district was 53%. Several factors appear to contribute to male involvement in the PMTCT program including age, residence, education level, knowledge on HIV, knowledge on PMTCT, accessibility of health facility, having weak perception for male involvement in PMTCT, having perception of ANC attendance being females' responsibility, ever use of khat, and ever use of cigarette. Conclusion. Geographical accessibility of health facility and male's knowledge on PMTCT should be improved to increase their involvement in PMTCT. PMID- 26146630 TI - Expression of Adiponectin Receptors on Peripheral Blood Leukocytes of Hypertensive Children Is Associated with the Severity of Hypertension. AB - The aim of the study was to find out whether peripheral blood leukocyte adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) protein expression patterns (flow cytometry) differ between the primary hypertension children (n = 57) and healthy controls (n = 19) and if their expression levels are related to selected clinical parameters. The group of 26 patients [AdipoR(-)] showed lower and the group of 31 patients [AdipoR(+)] showed higher AdipoRs protein expression than the control and each other (P < 0.01 for neutrophils, P < 0.05 for monocytes). The AdipoR(+) leukocytes expressed higher AdipoR1 mRNA levels (RT-PCR) than AdipoR(-) ones and controls (P = 0.022 and P = 0.007, resp.). Despite greater BMI, the AdipoR(-) patients had unchanged serum adiponectin levels. In contrast, AdipoR(+) patients had lower serum adiponectin concentrations than the AdipoR(-) ones and controls (P < 0.001). The AdipoR(+) patients had higher blood pressure (P = 0.042) and greater carotid intima-media thickness (P = 0.017) than the AdipoR(-) ones. The stage of hypertension was associated with increased neutrophil but not monocyte AdipoR1 density (AdipoR1 MFI) (P < 0.05). Severe ambulatory hypertension was presented more often in AdipoR(+) patients than in AdipoR(-) ones (51.6% versus 26.9%, resp.; P < 0.01). In conclusion, neutrophil AdipoRs upregulation was associated with early stages of vascular injury, hypertension severity, and low serum levels of adiponectin. PMID- 26146632 TI - Cortisol Response to Psychosocial Stress in Chinese Early Puberty Girls: Possible Role of Depressive Symptoms. AB - Objective. The present study aimed at investigating unique patterns of salivary cortisol reactivity and recovery in response to a social stressor among girls with early puberty and exploring possible role of depressive symptom in this association. Design. Case-control study. Patients. Fifty-six girls with early puberty and age- and body mass index- (BMI-) matched normal puberty controls (n = 56) were selected. Measurements. Salivary cortisol was measured in response to the Groningen Social Stress Test for Children. Results. Girls with early puberty had higher cortisol concentration at the end of the GSST (C3), cortisol concentration 20 min after the end of the GSST (C4), and AUC increment (AUCi) compared to non-early puberty girls. Depressive symptoms correlated with blunted HPA reactivity among girls with early puberty. Conclusion. This study demonstrated the disturbance effect of objectively examined early pubertal timing on HPA axis responses. It also suggested that stress reactivity might be blunted for individuals with depressive symptoms. PMID- 26146633 TI - Response of Arbuscular Mycorrhizal Fungi to Hydrologic Gradients in the Rhizosphere of Phragmites australis (Cav.) Trin ex. Steudel Growing in the Sun Island Wetland. AB - Within the rhizosphere, AM fungi are a sensitive variable to changes of botanic and environmental conditions, and they may interact with the biomass of plant and other microbes. During the vegetative period of the Phragmites australis growing in the Sun Island Wetland (SIW), the variations of AM fungi colonization were studied. Root samples of three hydrologic gradients generally showed AM fungi colonization, suggesting that AM fungi have the ability for adaptation to flooded habitats. There were direct and indirect hydrological related effects with respect to AM fungi biomass, which interacted simultaneously in the rhizosphere. Though water content in soil and reed growth parameters were both positively associated with AM fungi colonization, only the positive correlations between reed biomass parameters and the colonization could be expected, or both the host plant biomass and the AM fungi could be beneficial. The variations in response of host plant to the edaphic and hydrologic conditions may influence the effectiveness of the plant-mycorrhizal association. This study included a hydrologic component to better assess the role and distribution of AM fungi in wetland ecosystems. And because of that, the range of AM fungi was extended, since they actually showed a notable adaptability to hydrologic gradients. PMID- 26146634 TI - Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis? AB - Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM. PMID- 26146635 TI - Effects of the Chinese Herbal Formulation (Liu Wei Di Huang Wan) on the Pharmacokinetics of Isoflavones in Postmenopausal Women. AB - A combination of soy isoflavones and Liu Wei Di Huang Wan (LWDHW) is potentially effective for postmenopausal women with intolerable vasomotor episodes who are not suitable candidates for hormonal therapy. The objective of this open-label, three-phase, crossover study was to determine the influence of both single and multiple oral doses of LWDHW on isoflavone pharmacokinetics in healthy postmenopausal women. Eleven subjects were assigned to receive the following regimens in a fixed sequence with washout periods of at least one week: Phase A, a single oral dose of soy milk; Phase B, a single oral dose of soy milk coadministered with LWDHW; and Phase C, multiple oral doses of LWDHW for 14 days followed by a single oral dose of soy milk. Blood samples were collected and mixed with beta-glucuronidase/sulfatase to hydrolyze isoflavone conjugates to their respective aglycones (i.e., daidzein and genistein) and were determined using high performance liquid chromatography. The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). The results found no statistically significant differences in pharmacokinetic parameters of daidzein and genistein among the three regimens. PMID- 26146636 TI - Development of Microsatellite Markers Derived from Expressed Sequence Tags of Polyporales for Genetic Diversity Analysis of Endangered Polyporus umbellatus. AB - A large scale of EST sequences of Polyporales was screened in this investigation in order to identify EST-SSR markers for various applications. The distribution of EST sequences and SSRs in five families of Polyporales was analyzed, respectively. Mononucleotide was the most abundant type, followed by trinucleotide. Among five families, Ganodermataceae occupied the most SSR markers, followed by Coriolaceae. Functional prediction of SSR marker-containing EST sequences in Ganoderma lucidum obtained three main groups, namely, cellular component, biological process, and molecular function. Thirty EST-SSR primers were designed to evaluate the genetic diversity of 13 natural Polyporus umbellatus accessions. Twenty one EST-SSRs were polymorphic with average PIC value of 0.33 and transferability rate of 71%. These 13 P. umbellatus accessions showed relatively high genetic diversity. The expected heterozygosity, Nei's gene diversity, and Shannon information index were 0.41, 0.39, and 0.57, respectively. Both UPGMA dendrogram and principal coordinate analysis (PCA) showed the same cluster result that divided the 13 accessions into three or four groups. PMID- 26146637 TI - Minimally Invasive Spine Metastatic Tumor Resection and Stabilization: New Technology Yield Improved Outcome. AB - Spinal metastases compressing the spinal cord are a medical emergency and should be operated on if possible; however, patients' medical condition is often poor and surgical complications are common. Minimizing surgical extant, operative time, and blood loss can potentially reduce postoperative complications. This is a retrospective study describing the patients operated on in our department utilizing a minimally invasive surgery (MIS) approach to decompress and instrument the spine from November 2013 to November 2014. Five patients were operated on for thoracic or lumbar metastases. In all cases a unilateral decompression with expandable tubular retractor was followed by instrumentation of one level above and below the index level and additional screw at the index level contralateral to the decompression side. Cannulated fenestrated screws were used (Longitude FNS) and cement was injected to increase pullout resistance. Mean operative time was 134 minutes and estimated blood loss was minimal in all cases. Improvement was noticeable in neurological status, function, and pain scores. No complications were observed. Technological improvements in spinal instruments facilitate shorter and safer surgeries in oncologic patient population and thus reduce the complication rate. These technologies improve patients' quality of life and enable the treatment of patients with comorbidities. PMID- 26146638 TI - Regulation of Angiogenic Functions by Angiopoietins through Calcium-Dependent Signaling Pathways. AB - Angiopoietins are vascular factors essential for blood vessel assembly and correct organization and maturation. This study describes a novel calcium dependent machinery activated through Angiopoietin-1/2-Tie receptor system in HUVECs monolayer. Both cytokines were found to elicit intracellular calcium mobilization. Targeting intracellular Ca(2+) signaling, antagonizing IP3 with 2 APB or cADPR with 8Br-cADPR, was found to modulate in vitro angiogenic responses to Angiopoietins in a specific way. 2-APB and 8Br-cADPR impaired the phosphorylation of AKT and FAK induced by Ang-1 and Ang-2. On the other hand, phosphorylation of ERK1/2 and p38, as well as cell proliferation, was not affected by either inhibitor. The ability of ECs to migrate following Angs stimulation, evaluated by "scratch assay," was reduced by either 2-APB or 8Br cADPR following Ang-2 stimulation and only slightly affected by 2-APB in cells stimulated with Ang-1. These results identify a novel calcium-dependent machinery involved in the complex interplay regulating angiogenic processes showing that IP3- and cADPR-induced Ca(2+) release specifically regulates distinct Angs mediated angiogenic steps. PMID- 26146639 TI - Epoetin Alpha and Epoetin Zeta: A Comparative Study on Stimulation of Angiogenesis and Wound Repair in an Experimental Model of Burn Injury. AB - Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO) is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-alpha and EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80 degrees C water for 10 seconds. Mice were then randomized to receive EPO-alpha (400 units/kg/day/sc) or EPO-Z (400 units/kg/day/sc) or their vehicle (100 MUL/day/sc 0.9% NaCl solution). After 12 days, both EPO-alpha and EPO-Z increased VEGF protein expression. EPO-alpha caused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001). Our study showed that EPO-alpha and EPO-Z accelerated wound closure and angiogenesis; however EPO-alpha resulted more effectively in achieving complete skin regeneration. Our data suggest that EPO alpha and EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-alpha might be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling. PMID- 26146640 TI - IL-34 Suppresses Candida albicans Induced TNFalpha Production in M1 Macrophages by Downregulating Expression of Dectin-1 and TLR2. AB - Candida albicans is a fungus that is an opportunistic pathogen of humans. Normally, C. albicans exists as a harmless commensal and does not trigger inflammatory responses by resident macrophages in skin mucosa, which may be caused by a tolerance of skin macrophage to C. albicans. IL-34 is a recently discovered cytokine, constitutively expressed by keratinocytes in the skin. IL-34 binds to the receptor of M-CSF, thereby stimulating tissue macrophage maturation and differentiation. Resident macrophages exhibit phenotypic plasticity and may transform into inflammatory M1 macrophages for immunity or anti-inflammatory M2 macrophages for tissue repair. M1 macrophages produce higher levels of inflammatory cytokines such as TNFalpha in response to C. albicans stimulation. In this study, it was demonstrated that IL-34 attenuated TNFalpha production by M1 macrophages challenged with heat killed Candida (HKC). The molecular mechanism of IL-34 mediated suppression of HKC induced TNFalpha production by M1 macrophages was by the inhibition of M1 macrophage expression of key C. albicans pattern recognition receptors (PPRs), namely, Toll-like receptor (TLR) 2 and Dectin-1. The results of this study indicated that constitutive IL-34 expressed by skin keratinocytes might suppress resident macrophage responses to C. albicans colonisation by maintaining low levels TLR2 and Dectin-1 expression by macrophages. PMID- 26146641 TI - Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family. AB - CLCF-1 is a cytokine known for B-cell stimulation and for neurotrophic properties. We have identified CLCF-1 as a potential injurious factor in the human renal disease focal segmental glomerulosclerosis (FSGS). We investigated its effects on renal cells and renal function in in vitro and in vivo studies. Methods include measurement of the effect of CLCF-1 on phosphorylation of target molecules of the JAK/STAT pathway, on cytoskeleton and cell morphology in cultured podocytes, on albumin permeability of isolated rat glomeruli, and on tissue phosphorylation and urine albumin after acute or chronic CLCF-1 injection. In addition, cell sorting was performed to determine the presence of cells expressing CLCF-1 in spleen and bone marrow of normal mice and the effect of CLCF 1 infusion on splenic B-cell populations. CLCF-1 increased phosphorylation of STAT3 in multiple cell types, activated podocytes leading to formation of lamellipodia and decrease in basal stress fibers, increased glomerular albumin permeability, and increased STAT3 phosphorylation of peripheral blood cells and renal cortex. CLCF-1 increased urine albumin/creatinine ratio in mice and increased B-cell expression of IgG in mouse spleen. We conclude that CLCF-1 has potentially important systemic effects, alters podocyte function, and may contribute to renal dysfunction and albuminuria. PMID- 26146642 TI - Spontaneous Intestinal Tumorigenesis in Apc (/Min+) Mice Requires Altered T Cell Development with IL-17A. AB - The control of inflammatory diseases requires functional regulatory T cells (Tregs) with significant Gata-3 expression. Here we address the inhibitory role of Tregs on intestinal tumorigenesis in the Apc (/Min+) mouse model that resembles human familial adenomatous polyposis (FAP). Apc (/Min+) mice had a markedly increased frequency of Foxp3+ Tregs and yet decreased Gata-3 expression in the lamina propria. To address the role of heterozygous Apc gene mutation in Tregs, we generated Foxp3-Cre, Apc (flox/+) mice. Tregs from these mice effectively inhibited tumorigenesis comparable to wild type Tregs after adoptive transfer into Apc (/Min+) mice, demonstrating that the heterozygous Apc gene mutation in Tregs does not induce the loss of control over tumor microenvironment. Adoptive transfer of in vitro generated Apc (/Min+) iTregs (inducible Tregs) failed to inhibit intestinal tumorigenesis, suggesting that naive CD4 T cells generated from Apc (/Min+) mice thymus were impaired. We also showed that adoptively transferred IL-17A-deficient Apc (/Min+) Tregs inhibited tumor growth, suggesting that IL-17A was critical to impair the tumor regression function of Apc (/Min+) Tregs. Taken together, our results suggest that both T cell development in a functional thymus and IL-17A control the ability of Treg to inhibit intestinal tumorigenesis in Apc (/Min+) mice. PMID- 26146644 TI - Multiple Skin Abscesses and Myofibrosis of Bilateral Lower Limbs Following Repeated Intramuscular Injection of Pentazocine with Concomitant Tuberculous Infection. AB - INTRODUCTION: Prescription drug abuse is a major health problem across the globe. Various complications associated with repeated injection of pentazocine are reported in the literature, including skin fibrosis, skin abscesses and ulceration, abnormal skin pigmentation and fibrous myopathy. CASE REPORT: We present a case of 48 year male with history of pentazocine abuse. Patient developed multiple abscesses in both lower limbs with polymicrobial infection, one of them being mycobacterium tuberculosis. He also developed fibrous myopathy leading to stiff hip and knee. CONCLUSION: This case highlights the significance of the precaution that should be taken when prescribing opioid analgesics, such as pentazocine, as routine painkillers. With free over the counter access to these drugs in India and many developing countries, awareness of this complication is important so that unwanted side effects can be avoided. PMID- 26146643 TI - Vaccines for TB: Lessons from the Past Translating into Future Potentials. AB - Development of vaccines for infectious diseases has come a long way with recent advancements in adjuvant developments and discovery of new antigens that are capable of eliciting strong immunological responses for sterile eradication of disease. Tuberculosis (TB) that kills nearly 2 million of the population every year is also one of the highlights of the recent developments. The availability or not of diagnostic methods for infection has implications for the control of the disease by the health systems but is not related to the immune surveillance, a phenomenon derived from the interaction between the bacteria and their host. Here, we will review the immunology of TB and current vaccine candidates for TB. Current strategies of developing new vaccines against TB will also be reviewed in order to further discuss new insights into immunotherapeutic approaches involving adjuvant and antigens combinations that might be of potential for the control of TB. PMID- 26146645 TI - PRECISE:PRivacy-prEserving Cloud-assisted quality Improvement Service in hEalthcare. AB - Quality improvement (QI) requires systematic and continuous efforts to enhance healthcare services. A healthcare provider might wish to compare local statistics with those from other institutions in order to identify problems and develop intervention to improve the quality of care. However, the sharing of institution information may be deterred by institutional privacy as publicizing such statistics could lead to embarrassment and even financial damage. In this article, we propose a PRivacy-prEserving Cloud-assisted quality Improvement Service in hEalthcare (PRECISE), which aims at enabling cross-institution comparison of healthcare statistics while protecting privacy. The proposed framework relies on a set of state-of-the-art cryptographic protocols including homomorphic encryption and Yao's garbled circuit schemes. By securely pooling data from different institutions, PRECISE can rank the encrypted statistics to facilitate QI among participating institutes. We conducted experiments using MIMIC II database and demonstrated the feasibility of the proposed PRECISE framework. PMID- 26146647 TI - Methamphetamine Use among Homeless Former Foster Youth: The Mediating Role of Social Networks. AB - OBJECTIVES: Social network analysis can provide added causal insight into otherwise confusing epidemiologic findings in public health research. Although foster care and homelessness are risk factors for methamphetamine use, current research has failed to explicate why homeless youth with foster care experience engage in methamphetamine use at higher rates than other homeless young adults. This study examined the mediating effect of network engagement and time spent homeless on the relationship between foster care experience and recent methamphetamine use among homeless youth in Los Angeles. METHODS: Egocentric network data from a cross-sectional community-based sample (n = 652) of homeless youth aged 13-25 were collected from drop-in centers in Los Angeles. Questions addressed foster care experience, time spent homeless, methamphetamine use, and perceived drug use in social networks. Path analysis was performed in SAS to examine mediation. RESULTS: Controlling for all other variables, results of path analysis regarding recent methamphetamine use indicated a direct effect between foster care experience and recent methamphetamine use (B = .269, t = 2.73, p < .01). However, this direct effect became statistically nonsignificant when time spent homeless and network methamphetamine use were added to the model, and indirect paths from time spent homeless and network methamphetamine use became statistically significant. CONCLUSIONS: Foster care experience influenced recent methamphetamine use indirectly through time spent homeless and methamphetamine use by network members. Efforts to reduce methamphetamine use should focus on securing stable housing and addressing network interactions among homeless former foster youth. PMID- 26146646 TI - In vitro and in vivo model systems used in prostate cancer research. AB - New incidence of prostate cancer is a major public health issue in the Western world, and has been rising in other areas of the globe in recent years. In an effort to understanding the molecular pathogenesis of this disease, numerous cell models have been developed, arising mostly from patient biopsies. The introduction of the genetically engineered mouse in biomedical research has allowed the development of murine models that allow for the investigation of tumorigenic and metastatic processes. Current challenges to the field include lack of an animal model that faithfully recapitulates bone metastasis of prostate cancer. PMID- 26146648 TI - Evolution of microRNA (miRNA) Structure and Function in Plants and Animals: Relevance to Aging and Disease. PMID- 26146649 TI - An Exploration of the Sexual Behaviors of Emerging Adult Men Attending a Historically Black College/University. AB - The purpose of this study was to provide formative data on the sexual behaviors of emerging adult Black men who attended a historically Black college/university. A convenience sample of 19 participants completed a demographic questionnaire and a semi-structured interview. This study utilized a phenomenological qualitative approach to explore the role of the developmental stage that emerging adulthood has on sexual health. Some of the major themes that emerged included maturation, sexual decision-making, respectability, a future orientation, and masculinity. Despite sexual initiation beginning prior to entering college, participants discussed how the college environment presented them with new information, experiences, and attitudes. This study provides useful information for the future investigation of emerging adult Black men who attend HBCUs. PMID- 26146650 TI - Neurobiological mechanisms of social attachment and pair bonding. AB - Species have evolved diverse social behavior and mating strategies in response to selective forces in their environments. While promiscuity is the predominant mating strategy across most vertebrate taxa, convergent evolution of monogamous mating systems has occurred multiple times across distant lineages. Monogamous behavior is thought to be facilitated by a neurobiological capacity to form and maintain selective social attachments, or pair bonds, with a mating partner. The neural mechanisms of pair bonding behavior have been investigated most rigorously in Microtine rodents, which exhibit diverse social organizations. These studies have highlighted mesolimbic dopamine pathways, social neuropeptides (oxytocin and vasopressin), and other neural systems as integral factors in the formation, maintenance, and expression of pair bonds. PMID- 26146651 TI - Endovascular Treatment of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: Complications, Neurological Outcomes, and Radiographic Results. AB - INTRODUCTION: Idiopathic intracranial hypertension (IIH) may result in a chronic debilitating disease. Dural venous sinus stenosis with a physiologic venous pressure gradient has been identified as a potential etiology in a number of IIH patients. Intracranial venous stenting has emerged as a potential treatment alternative. METHODS: A systematic review was carried out to identify studies employing venous stenting for IIH. RESULTS: From 2002 to 2014, 17 studies comprising 185 patients who underwent 221 stenting procedures were reported. Mean prestent pressure gradient was 20.1 mmHg (95% CI 19.4-20.7 mmHg) with a mean poststent gradient of 4.4 mmHg (95% CI 3.5-5.2 mmHg). Complications occurred in 10 patients (5.4%; 95% CI 4.7-5.4%) but were major in only 3 (1.6%). At a mean clinical follow-up of 22 months, clinical improvement was noted in 130 of 166 patients with headaches (78.3%; 95% CI 75.8-80.8%), 84 of 89 patients with papilledema (94.4%; 95% CI 92.1-96.6%), and 64 of 74 patients with visual symptoms (86.5%; 95% CI 83.0-89.9%). In-stent stenosis was noted in six patients (3.4%; 95% CI 2.5-4.3%) and stent-adjacent stenosis occurred in 19 patients (11.4%; 95% CI 10.4-12.4), resulting in restenting in 10 patients. CONCLUSION: In IIH patients with venous sinus stenosis and a physiologic pressure gradient, venous stenting appears to be a safe and effective therapeutic option. Further studies are necessary to determine the long-term outcomes and the optimal management of medically refractory IIH. PMID- 26146652 TI - Structural, Morphological, and Electron Transport Studies of Annealing Dependent In2O3 Dye-Sensitized Solar Cell. AB - Indium oxide (In2O3) thin films annealed at various annealing temperatures were prepared by using spin-coating method for dye-sensitized solar cells (DSSCs). The objective of this research is to enhance the photovoltaic conversion efficiency in In2O3 thin films by finding the optimum annealing temperature and also to study the reason for high and low performance in the annealed In2O3 thin films. The structural and morphological characteristics of In2O3 thin films were studied via XRD patterns, atomic force microscopy (AFM), field-emission scanning electron microscopy (FESEM), EDX sampling, and transmission electron microscopy (TEM). The annealing treatment modified the nanostructures of the In2O3 thin films viewed through FESEM images. The In2O3-450 degrees C-based DSSC exhibited better photovoltaic performance than the other annealed thin films of 1.54%. The electron properties were studied by electrochemical impedance spectroscopy (EIS) unit. The In2O3-450 degrees C thin films provide larger diffusion rate, low recombination effect, and longer electron lifetime, thus enhancing the performance of DSSC. PMID- 26146653 TI - Radiation-Associated Toxicities in Obese Women with Endometrial Cancer: More Than Just BMI? AB - PURPOSE: The study characterizes the impact of obesity on postoperative radiation associated toxicities in women with endometrial cancer (EC). MATERIAL AND METHODS: A retrospective study identified 96 women with EC referred to a large urban institution's radiation oncology practice for postoperative whole pelvic radiotherapy (WPRT) and/or intracavitary vaginal brachytherapy (ICBT). Demographic and clinicopathologic data were obtained. Toxicities were graded according to RTOG Acute Radiation Morbidity Scoring Criteria. Follow-up period ranged from 1 month to 11 years (median 2 years). Data were analyzed by chi(2), logistic regression, and recursive partitioning analyses. RESULTS: 68 EC patients who received WPRT and/or ICBT were analyzed. Median age was 52 years (29-73). The majority were Hispanic (71%). Median BMI at diagnosis was 34.5 kg/m(2) (20.5-56.6 kg/m(2)). BMI was independently associated with radiation-related cutaneous (p = 0.022) and gynecologic-related (p = 0.027) toxicities. Younger women also reported more gynecologic-related toxicities (p = 0.039). Adjuvant radiation technique was associated with increased gastrointestinal- and genitourinary related toxicities but not gynecologic-related toxicity. CONCLUSIONS: Increasing BMI was associated with increased frequency of gynecologic and cutaneous radiation-associated toxicities. Additional studies to critically evaluate the radiation treatment dosing and treatment fields in obese EC patients are warranted to identify strategies to mitigate the radiation-associated toxicities in these women. PMID- 26146654 TI - Granulocyte-Colony Stimulating Factor Increases Cerebral Blood Flow via a NO Surge Mediated by Akt/eNOS Pathway to Reduce Ischemic Injury. AB - Granulocyte-colony stimulating factor (G-CSF) protects brain from ischemic/reperfusion (I/R) injury, and inhibition of nitric oxide (NO) synthases partially reduces G-CSF protection. We thus further investigated the effects of G CSF on ischemia-induced NO production and its consequence on regional cerebral blood flow (rCBF) and neurological deficit. Endothelin-1 (ET-1) microinfused above middle cerebral artery caused a rapid reduction of rCBF (ischemia) which lasted for 30 minutes and was followed by a gradual recovery of blood flow (reperfusion) within the striatal region. Regional NO concentration increased rapidly (NO surge) during ischemia and recovered soon to the baseline. G-CSF increased rCBF resulting in shorter ischemic duration and an earlier onset of reperfusion. The enhancement of the ischemia-induced NO by G-CSF accompanied by elevation of phospho-Akt and phospho-eNOS was noted, suggesting an activation of Akt/eNOS. I/R-induced infarct volume and neurological deficits were also reduced by G-CSF treatment. Inhibition of NO synthesis by L-N(G)-Nitroarginine Methyl Ester (L-NAME) significantly reduced the effects of G-CSF on rCBF, NO surge, infarct volume, and neurological deficits. We conclude that G-CSF increases rCBF through a NO surge mediated by Akt/eNOS, which partially contributes to the beneficial effect of G-CSF on brain I/R injury. PMID- 26146655 TI - Antimicrobial Analysis of an Antiseptic Made from Ethanol Crude Extracts of P. granatum and E. uniflora in Wistar Rats against Staphylococcus aureus and Staphylococcus epidermidis. AB - INTRODUCTION: Surgical site infection remains a challenge for hospital infection control, especially when it relates to skin antisepsis in the surgical site. OBJECTIVE: To analyze the antimicrobial activity in vivo of an antiseptic from ethanol crude extracts of P. granatum and E. uniflora against Gram-positive and Gram-negative bacteria. METHODS: Agar drilling and minimal inhibitory tests were conducted for in vitro evaluation. In the in vivo bioassay were used Wistar rats and Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 14990). Statistical analysis was performed through variance analysis and Scott Knott cluster test at 5% probability and significance level. RESULTS: In the in vitro, ethanolic extracts of Punica granatum and Eugenia uniflora and their combination showed the best antimicrobial potential against S. epidermidis and S. aureus. In the in vivo bioassay against S. epidermidis, there was no statistically significant difference between the tested product and the patterns used after five minutes of applying the product. CONCLUSION: The results indicate that the originated product is an antiseptic alternative source against S. epidermidis compared to chlorhexidine gluconate. It is suggested that further researches are to be conducted in different concentrations of the test product, evaluating its effectiveness and operational costs. PMID- 26146656 TI - A Strategic Study about Quality Characteristics in e-Health Systems Based on a Systematic Literature Review. AB - e-Health Systems quality management is an expensive and hard process that entails performing several tasks such as analysis, evaluation, and quality control. Furthermore, the development of an e-Health System involves great responsibility since people's health and quality of life depend on the system and services offered. The focus of the following study is to identify the gap in Quality Characteristics for e-Health Systems, by detecting not only which are the most studied, but also which are the most used Quality Characteristics these Systems include. A strategic study is driven in this paper by a Systematic Literature Review so as to identify Quality Characteristics in e-Health. Such study makes information and communication technology organizations reflect and act strategically to manage quality in e-Health Systems efficiently and effectively. As a result, this paper proposes the bases of a Quality Model and focuses on a set of Quality Characteristics to enable e-Health Systems quality management. Thus, we can conclude that this paper contributes to implementing knowledge with regard to the mission and view of e-Health (Systems) quality management and helps understand how current researches evaluate quality in e-Health Systems. PMID- 26146657 TI - Unruptured Cerebral Aneurysms: Evaluation and Management. AB - The evolution of imaging techniques and their increased use in clinical practice have led to a higher detection rate of unruptured intracranial aneurysms. The diagnosis of an unruptured intracranial aneurysm is a source of significant stress to the patient because of the concerns for aneurysmal rupture, which is associated with substantial rates of morbidity and mortality. Therefore, it is important that decisions regarding optimum management are made based on the comparison of the risk of aneurysmal rupture with the risk associated with intervention. This review provides a comprehensive overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management options for unruptured intracranial aneurysms based on the current evidence in the literature. Furthermore, the authors discuss the genetic abnormalities associated with intracranial aneurysm and current guidelines for screening in patients with a family history of intracranial aneurysms. Since there is significant controversy in the optimum management of small unruptured intracranial aneurysms, we provided a systematic approach to their management based on patient and aneurysm characteristics as well as the risks and benefits of intervention. PMID- 26146659 TI - Communicating Effectively about Organ Donation: A Randomized Trial of a Behavioral Communication Intervention to Improve Discussions about Donation. AB - BACKGROUND: Families' refusal to authorize solid organ donation contributes to the organ deficit in the United States. The importance of communication to reducing refusal to requests for solid organ donation at the bedside and thus increasing the supply of transplantable organs cannot be overstated. This research compares two versions of an innovative communication skills training program for Organ Procurement Organization (OPO) request staff, Communicating Effectively About Donation (CEaD), designed to improve the quantity and quality of organ donation discussions with family decision makers (FDM) of deceased patients. METHODS: We conducted a parallel-group randomized controlled trial of the CEaD intervention, comparing an online only version of the training (CEaD1) with the online version bolstered with in-person practice and feedback (CEaD2). Survey and interview data were collected from 1,603 FDMs and 273 requesters to assess the impact of both versions of the CEaD on requesters' communication skills and behaviors; the rate of family authorization to solid organ donation were obtained from administrative data provided by 9 OPOs. RESULTS: Results revealed higher rates of authorization for requesters with less tenure (78% to 89%, p < .03) for both versions; however, CEaD1 also increased authorization rates for requesters with three or more years of experience (89% to 92%, p < .03). Both conditions resulted in an improvement in overall communication quality. CONCLUSIONS: We conclude that the CEaD was effective in improving requesters' communication skills, rates of family authorization to organ donation, and the overall quality of the donation experience. PMID- 26146658 TI - Network Mechanisms Generating Abnormal and Normal Hippocampal High-Frequency Oscillations: A Computational Analysis. AB - High-frequency oscillations (HFOs) are an intriguing potential biomarker for epilepsy, typically categorized according to peak frequency as either ripples (100-250 Hz) or fast ripples (>250 Hz). In the hippocampus, fast ripples were originally thought to be more specific to epileptic tissue, but it is still very di cult to distinguish which HFOs are caused by normal versus pathological brain activity. In this study we use a computational model of hippocampus to investigate possible network mechanisms underpinning normal ripples, pathological ripples, and fast ripples. Our results unify several prior findings regarding HFO mechanisms, and also make several new predictions regarding abnormal HFOs. We show that HFOs are generic, emergent phenomena whose characteristics reflect a wide range of connectivity and network input. Although produced by di erent mechanisms, both normal and abnormal HFOs generate similar ripple frequencies, underscoring that peak frequency is unable to distinguish the two. Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing. In addition, fast ripples transiently and sporadically arise from the precise conditions that produce abnormal ripples. Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner. These results provide a generic, network based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples. PMID- 26146660 TI - MYROIDES INFECTION IN A BABOON AFTER PROLONGED PIG KIDNEY GRAFT SURVIVAL. AB - BACKGROUND: Immunosuppressed patients and experimental nonhuman primates are at risk of opportunistic infection. We report a Myroides spp infection in an immunosuppressed baboon that had received a life-supporting kidney from a genetically-engineered pig. CASE REPORT: The baboon received a costimulation blockade-based immunosuppressive regimen as well as two anti-inflammatory agents (tocilizumab and etanercept). Although the pig kidney functioned well, approximately four months after the transplant the baboon became less active and ate and drank poorly. On day 136, it collapsed and died despite inotropic and fluid support. A blood culture drawn before death grew Myroides spp. DISCUSSION AND CONCLUSIONS: To our knowledge, Myroides spp has not been reported as a cause of opportunistic infection in either patients with organ allotransplants or experimental animals. We summarize what is known about this rare organism, and suggest it should be considered in any immunocompromised patient or animal. In the present case, we suggest the baboon died of circulatory shock following infection through an indwelling intravenous catheter. PMID- 26146661 TI - Clinical and Genetic Factors Associated with Cutaneous Squamous Cell Carcinoma in Kidney and Heart Transplant Recipients. AB - BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) occurs with higher frequency and recurrence rates, increased morbidity and mortality, and more aggressive metastasis in kidney and heart transplant recipients compared to the general population but all transplant recipients do not develop cSCC. In addition, the phenotypic expression of cSCC among transplant recipients can vary between mild disease to extensive recurrent metastatic disease. These clinically observed differences in occurrence and severity of cSCC among transplant recipients suggest the possibility that an underlying genetic component might modify risk. METHODS: We identified 88 white post-transplant cSCC cases (71 kidney and 17 heart) and 300 white post-transplant controls (265 kidney and 35 heart) using a DNA biobank linked with de-identified electronic medical records. Logistic regression was used to determine adjusted odds ratios (OR) for clinical characteristics and single nucleotide polymorphisms (SNP) associated with cSCC in both a candidate SNP and genome wide analysis. RESULTS: Age (OR 1.08 [1.05-1.11], p<0.001) and azathioprine exposure (OR 8.64 [3.92-19.03], p<0.001) were significantly associated while gender, smoking tobacco use, dialysis duration and immunosuppression duration were not. Ten candidate SNPs previously associated with non-melanoma skin cancer in the general population were significantly associated with cSCC in transplant recipients. Genome wide association analysis implicated SNPs in genes previously associated with malignancy, CSMD1 (OR 3.14 [1.90-5.20]) and CACNA1D (OR 2.67 [1.73-4.10]). CONCLUSIONS: This study shows an association of increasing age and azathioprine exposure with cSCC and confirms a genetic contribution for cSCC development in kidney and heart transplant recipients. PMID- 26146663 TI - Clinician perspectives on potentially avoidable hospitalizations in patients with cancer. PMID- 26146662 TI - The Choice of Enzyme for Human Pancreas Digestion is a Critical Factor for Increasing the Success of Islet Isolation. AB - BACKGROUND: We evaluated three commercially available enzymes for pancreatic digestion by comparing key parameters during the islet isolation process, as well as islet quality post-isolation. METHODS: Retrospectively compared and analyzed islet isolations from pancreata using three different enzyme groups: Liberase HI (n=63), Collagenase NB1/Neutral Protease (NP) (n=43), and Liberase Mammalian Tissue Free Collagenase/Thermolysin (MTF C/T) (n=115). A standardized islet isolation and purification method was used. Islet quality assessment was carried out using islet count, viability, in vitro glucose-stimulated insulin secretion (GSIS), glucose-stimulated oxygen consumption rate (DeltaOCR), and in vivo transplantation model in mice. RESULTS: Donor characteristics were not significantly different among the three enzyme groups used in terms of age, sex, hospital stay duration, cause of death, body mass index (BMI), hemoglobin A1c (HbA1c), cold ischemia time (CIT), and pancreas weight. Digestion efficacy (percentage of digested tissue by weight) was significantly higher in the Liberase MTF C/T group (73.5 +/- 1.5 %) when compared to the Liberase HI group (63.6 +/- 2.3 %) (p<0.001) and the Collagenase NB1/NP group (61.7 +/- 2.9%) (p<0.001). The stimulation index for GSIS was significantly higher in the Liberase MTF C/T group (5.3 +/- 0.5) as compared to the Liberase HI (2.9 +/- 0.2) (p<0.0001) and the Collagenase NB1/NP (3.6 +/- 2.9) (p=0.012) groups. Furthermore, the Liberase MTF C/T enzymes showed the highest success rate of transplantation in diabetic NOD Scid mice (65%), which was significantly higher than the Liberase HI (42%, p=0.001) and the Collagenase NB1/NP enzymes (41%, p<0.001). CONCLUSIONS: Liberase MTF C/T is superior to Liberase HI and Collagenase NB1/NP in terms of digestion efficacy and glucose-stimulated insulin secretion in vitro. Moreover, Liberase MTF C/T had a significantly higher success rate of transplantation in diabetic NOD Scid mice compared to Liberase HI and Collagenase NB1/NP enzymes. PMID- 26146665 TI - Clinical Questions in Online Health Communities: The Case of "See your doctor" Threads. AB - Online health communities are known to provide psychosocial support. However, concerns for misinformation being shared around clinical information persist. An existing practice addressing this concern includes monitoring and, as needed, discouraging asking clinical questions in the community. In this paper, I examine such practice where moderators redirected patients to see their health care providers instead of consulting the community. I observed that, contrary to common beliefs, community members provided constructive tips and persuaded the patients to see doctors rather than attempting to make a diagnosis or give medical advice. Moderators' posts on redirecting patients to see their providers were highly associated with no more follow up replies, potentially hindering active community dynamic. The findings showed what is previously thought of as a solution-quality control through moderation-might not be best and that the community, in coordination with moderators, can provide critical help in addressing clinical questions and building constructive information sharing community environment. PMID- 26146666 TI - Summaries for Patients. Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss. PMID- 26146667 TI - Summaries for Patients. The Obesity Paradox in Type 2 Diabetes Mellitus. PMID- 26146664 TI - Association Between NRAS and BRAF Mutational Status and Melanoma-Specific Survival Among Patients With Higher-Risk Primary Melanoma. AB - IMPORTANCE: NRAS and BRAF mutations in melanoma inform current treatment paradigms, but their role in survival from primary melanoma has not been established. Identification of patients at high risk of melanoma-related death based on their primary melanoma characteristics before evidence of recurrence could inform recommendations for patient follow-up and eligibility for adjuvant trials. OBJECTIVE: To determine tumor characteristics and survival from primary melanoma by somatic NRAS and BRAF status. DESIGN, SETTING, AND PARTICIPANTS: A population-based study with a median follow-up of 7.6 years (through 2007), including 912 patients from the United States and Australia in the Genes, Environment, and Melanoma (GEM) Study, with first primary cutaneous melanoma diagnosed in the year 2000 and analyzed for NRAS and BRAF mutations. MAIN OUTCOMES AND MEASURES: Tumor characteristics and melanoma-specific survival of primary melanoma by NRAS and BRAF mutational status. RESULTS: The melanomas were 13% NRAS+, 30% BRAF+, and 57% with neither NRAS nor BRAF mutation (wildtype [WT]). In a multivariable model including clinicopathologic characteristics, relative to WT melanoma (with results reported as odds ratios [95% CIs]), NRAS+ melanoma was associated with presence of mitoses (1.8 [1.0-3.3]), lower tumor infiltrating lymphocyte (TIL) grade (nonbrisk, 0.5 [0.3-0.8]; and brisk, 0.3 [0.5 0.7] [vs absent TILs]), and anatomic site other than scalp/neck (0.1 [0.01-0.6] for scalp/neck vs trunk/pelvis), and BRAF+ melanoma was associated with younger age (ages 50-69 years, 0.7 [0.5-1.0]; and ages >70 years, 0.5 [0.3-0.8] [vs <50 years]), superficial spreading subtype (nodular, 0.5 [0.2-1.0]; lentigo maligna, 0.4 [0.2-0.7]; and unclassified/other, 0.2 [0.1-0.5] [vs superficial spreading]), and presence of mitoses (1.7 [1.1-2.6]) (P < .05 for all). There was no significant difference in melanoma-specific survival (reported as hazard ratios [95% CIs]) for melanoma harboring mutations in NRAS (1.7 [0.8-3.4]) or BRAF (1.5 [0.8-2.9]) compared with WT melanoma, as adjusted for age, sex, site, American Joint Committee on Cancer (AJCC) tumor stage, TIL grade, and study center. However, melanoma-specific survival was significantly poorer for higher-risk (T2b or higher stage) tumors with NRAS (2.9 [1.1-7.7]) or BRAF (3.1 [1.2-8.5]) mutations (P = .04) but not for lower-risk (T2a or lower) tumors with NRAS (0.9 [0.3-3.0]) or BRAF (0.6 [0.2-1.7]) (P = .65), as adjusted for age, sex, site, AJCC tumor stage, TIL grade, and study center. CONCLUSIONS AND RELEVANCE: Lower TIL grade for NRAS+ melanoma suggests it has a more immunosuppressed microenvironment, which may affect its response to immunotherapies. The approximate 3-fold increased risk of death for higher-risk tumors harboring NRAS or BRAF mutations after adjusting for other prognostic factors compared with WT melanomas indicates that the prognostic implication of these mutations deserves further investigation, particularly in higher-AJCC stage primary melanomas. PMID- 26146668 TI - Summaries for Patients. Screening for Thyroid Dysfunction: U.S. Preventive Services Task Force Recommendation. PMID- 26146669 TI - [The PsychKHG in Baden-Wurttemberg: reduction of the rights of the mentally ill over the weekend?]. PMID- 26146670 TI - [Assisted suicide--(k) a topic for psychiatry?]. PMID- 26146671 TI - [Lubisch B, Roth-Sackenheim C. We need a direct degree program in Psychotherapy - Pro & Contra. Psychiat Prax 2015; 42: 66-67]. PMID- 26146672 TI - Introduction to the 5th ADEA International Women's Leadership Conference Proceedings. PMID- 26146673 TI - [From Dementia is neurocognitive disorder. Finzen A. German version of the DSM. 5 Psychiat Prax 2015; 42: 109-110]. PMID- 26146674 TI - Authors' reply. PMID- 26146676 TI - Genetic traces of mankind's migrations. PMID- 26146675 TI - Growth-dependent bacterial susceptibility to ribosome-targeting antibiotics. AB - Bacterial growth environment strongly influences the efficacy of antibiotic treatment, with slow growth often being associated with decreased susceptibility. Yet in many cases, the connection between antibiotic susceptibility and pathogen physiology remains unclear. We show that for ribosome-targeting antibiotics acting on Escherichia coli, a complex interplay exists between physiology and antibiotic action; for some antibiotics within this class, faster growth indeed increases susceptibility, but for other antibiotics, the opposite is true. Remarkably, these observations can be explained by a simple mathematical model that combines drug transport and binding with physiological constraints. Our model reveals that growth-dependent susceptibility is controlled by a single parameter characterizing the 'reversibility' of ribosome-targeting antibiotic transport and binding. This parameter provides a spectrum classification of antibiotic growth-dependent efficacy that appears to correspond at its extremes to existing binary classification schemes. In these limits, the model predicts universal, parameter-free limiting forms for growth inhibition curves. The model also leads to nontrivial predictions for the drug susceptibility of a translation mutant strain of E. coli, which we verify experimentally. Drug action and bacterial metabolism are mechanistically complex; nevertheless, this study illustrates how coarse-grained models can be used to integrate pathogen physiology into drug design and treatment strategies. PMID- 26146677 TI - Jeremy Wolfe. PMID- 26146678 TI - Cradoscrupocellaria, a new bryozoan genus for Scrupocellaria bertholletii (Audouin) and related species (Cheilostomata, Candidae): taxonomy, biodiversity and distribution. AB - A new genus, Cradoscrupocellaria n. gen., is erected for Scrupocellaria bertholletii (Audouin, 1826), reported as widespread in tropical and subtropical waters. Here we select a neotype of this species in order to establish its identity and distinguish it from morphologically similar species. We include redescriptions and figures of additional species now assigned to this new genus: Cradoscrupocellaria curacaoensis (Fransen, 1986) n. comb., Cradoscrupocellaria hirsuta (Jullien & Calvet, 1903) n. comb., and Cradoscrupocellaria macrorhyncha (Gautier, 1962) n. comb. Five additional species are as-signed to the genus: Cradoscrupocellaria ellisi (Vieira & Spencer Jones, 2012) n. comb., Cradoscrupocellaria nanshaensis (Liu, 1991) n. comb., Cradoscrupocellaria reptans (Linnaeus, 1758) n. comb., Cradoscrupocellaria serrata (Waters, 1909) n. comb., and Cradoscrupocellaria tenuirostris (Osburn, 1950) n. comb. Eighteen new species are described: Cra-doscrupocellaria aegyptiana n. sp., Cradoscrupocellaria arisaigensis n. sp., Cradoscrupocellaria atlantica n. sp., Cradoscrupocellaria calypso n. sp., Cradoscrupocellaria floridana n. sp., Cradoscrupocellaria galapagensis n. sp., Cradoscrupocellaria gautieri n. sp., Cradoscrupocellaria gorgonensis n. sp., Cradoscrupocellaria hastingsae n. sp., Cradoscrupocellaria insularis n. sp., Cradoscrupocellaria jamaicensis n. sp., Cradoscrupocellaria lagaaiji n. sp., Cradoscrupocellaria macrorhynchoides n. sp., Cradoscrupocellaria makua n. sp., Cradoscrupocellaria marcusorum n. sp., Cradoscrupocellaria normani n. sp., Cradoscrupocellaria odonoghuei n. sp., and Cradoscrupocellaria osburni n. sp. PMID- 26146679 TI - Australian Marsh Beetles (Coleoptera: Scirtidae) 4. Two new genera, Austrocyphon and Tasmanocyphon. AB - The related new genera Austrocyphon and Tasmanocyphon are erected for 42 small Australian marsh beetles resembling members of the genus Cyphon Paykull in habitus. They are distinguished from Cyphon. Only males are known of most species but for two of them larvae and pupae are also available. Austrocyphon species occur in all Australian Federal States, and one species is Australasian and shared with Papua New Guinea. The following species are included: Austrocyphon acaciae sp. n., A. aculeatus sp. n., A. acustropicus sp. n., A. adelaidae (Blackburn), A. asper sp. n., A. bidens sp. n., A. bifidus sp. n., A. charon sp. n., A. crinitus (Klausnitzer), A. curvispina, sp. n., A. deserticola sp. n., A. doctus (Lea), A. enigmaticus sp. n., A. excisus sp. n., A. fenestratus (Blackburn), A. flagellifer sp. n., A. furcatus sp. n., A. hamatus sp. n., A. harpago sp. n., A. leptophallus sp. n., A. linguatus sp. n., A. lobatus sp. n., A. neptunus sp. n., A. noctua sp. n., A. ovensensis (Blackburn), A. papilio sp. n., A. perdoctus sp. n., A. pictus (Blackburn), A. quadridens sp. n., A. quinquespinosus sp. n., A. robustus sp. n., A. setifer sp. n., A. spiculifer sp. n., A. stylatus sp. n., A. stylifer sp. n., A. submersus sp. n., A. tinea sp. n., A. tomweiri sp. n., A. tribulator sp. n., A. tropicus sp. n., A. unguiculatus sp. n., A. wattsi sp. n.Tasmanocyphon is endemic to Tasmania, and only the adult male is known. The genus is monotypic, including only T. heideae, sp. n. PMID- 26146680 TI - Review of the genus Ypsolopha Latreille, 1796 from China (Lepidoptera: Ypsolophidae). AB - We present a review of the Chinese species of the genus Ypsolopha Latreille. Of the 60 species treated herein, 21 species are described as new: Y. flaviterminata sp. nov., Y. flavida sp. nov., Y. albula sp. nov., Y. longisaccata sp. nov., Y. fascimaculata sp. nov., Y. mucronulata sp. nov., Y. bicostata sp. nov., Y. latiuscula sp. nov., Y. purpurata sp. nov., Y. minuta sp. nov., Y. allochroa sp. nov., Y. brevivalva sp. nov., Y. longifloccosa sp. nov., Y. paristrigosa sp. nov., Y. umbrina sp. nov., Y. varidentella sp. nov., Y. capitalba sp. nov., Y. triangula sp. nov., Y. aurea sp. nov., Y. chlorina sp. nov., and Y. bisticta sp. nov.; eight species are newly recorded for the Chinese fauna: Ypsolopha acerella Ponomarenko, Sohn et Zinchenko, Y. sarmaticella (Rebel), Y. albiramella (Mann), Y. altissimella (Chretien), Y. albistriata (Issiki), Y. longa Moriuti, Y. saitoi Moriuti and Y. falcella (Denis & Schiffermuller). A new species-group, the albiramella-group, is defined. Ypsolopha hebeiensis Yang, Y. nigrofasciata Yang, Y. ulingensis Yang and Y. diana (Caradja) are redescribed. One synonym is established: Y. sordidella Sohn et Wu, 2010 syn. n. (= Y. sordida Sohn et Wu, 2010). The male genitalia of Y. japonica Moriuti, Y. altissimella (Chretien), Y. diana (Caradja), and the female genitalia of Y. hebeiensis Yang, Y. sarmaticella (Rebel), Y. altissimella (Chretien), Y. ulingensis Yang, Y. helva Sohn et Wu and Y. diana (Caradja) are described for the first time. Photographs of the adults, wing venations and genitalia are provided. Keys for the identification of species groups as well as the species of each species-group are included, along with a distribution map of all the known Chinese species. PMID- 26146681 TI - Generic classification of the Archiborborinae (Diptera: Sphaeroceridae), with a revision of Antrops Enderlein, Coloantrops gen. nov., Maculantrops gen. nov., Photoantrops gen. nov., and Poecilantrops gen. nov. AB - The Archiborborinae comprise a diverse clade of flies in the family Sphaeroceridae. We here revise the generic classification, redefining the genus Antrops Enderlein and naming 5 new genera: Boreantrops gen. nov., Coloantrops gen. nov., Maculantrops gen. nov., Photoantrops gen. nov., and Poecilantrops gen. nov. The genus Archiborborus, until recently a paraphyletic assemblage including most of the described species in the subfamily, is treated as a junior synonym of Antrops (syn. nov.) We revise the genera Antrops (53 species, including 40 sp. nov.: Antrops anovariegatus, Antrops aurantifemur, Antrops baeza, Antrops bellavista, Antrops biflavus, Antrops bucki, Antrops carpishensis, Antrops cochabamba, Antrops cochinoca, Antrops coniobaptos, Antrops coroico, Antrops cotopaxi, Antrops didactylos, Antrops diversipennis, Antrops eurus, Antrops fulgiceps, Antrops fuliginosus, Antrops guandera, Antrops guaramacalensis, Antrops inca, Antrops juninensis, Antrops mucarensis, Antrops niger, Antrops papallacta, Antrops pecki, Antrops podocarpus, Antrops quadrilobus, Antrops siberia, Antrops sierrazulensis, Antrops tachira, Antrops tequendama, Antrops tetrastichus, Antrops tumbrensis, Antrops unduavi, Antrops variegatus, Antrops versabilis, Antrops vittatus, Antrops yungas, and Antrops zongo and the following comb. nov.: Antrops annulatus (Richards), Antrops chaetosus (Richards), Antrops femoralis (Blanchard), Antrops hirtus (Bigot), Antrops maculipennis (Duda), Antrops maximus (Richards), Antrops microphthalmus (Richards), Antrops quadrinotus (Bigot), Antrops setosus (Duda), Antrops simplicimanus (Richards), Antrops nitidicollis (Becker), and Antrops orbitalis (Duda)), Coloantrops (1 species: Coloantrops daedalus, sp. nov.), Maculantrops (2 species, Maculantrops hirtipes (Macquart) comb. nov. and Maculantrops altiplanus, sp. nov.), Photoantrops (1 species: Pho-toantrops echinus sp. nov.), and Poecilantrops (10 species: Poecilantrops baorucensis, Poecilantrops boraceiensis, Poecilantrops crocidosternum, Poecilantrops dominicus, Poecilantrops flavifemur, Poecilantrops marensis, Poecilantrops plaumanni, Poecilantrops psilosternum, Poecilantrops stellans, Poecilantrops vittifrons, all sp. nov.). Six additional species of Antrops and two of Poecilantrops known from females only are diagnosed but not described. The genus Boreantrops is described for two species (Boreantrops mexicanus (Steyskal) comb. nov., and Boreantrops calceatus (Duda) comb. nov.). Boreantrops includes a number of new species but is not fully revised here. New synonyms at the species level are: Antrops femoralis (Blanchard 1852) = Archiborborus argentinensis Papp 1977, and Archiborborus submaculatus Duda 1921, both syn. nov.; Antrops hirtus (Bigot 1888) = Archiborborus edwardsi Richards 1931, syn. nov.; Antrops quadrinotus (Bigot 1888) = Archiborborus albicans Richards 1931, Archiborborus chilensis Richards 1931, Archiborbo-rus koenigi Duda 1932, all syn. nov.; Maculantrops hirtipes (Macquart 1844) = Copromyza alternata Rondani 1868, syn. nov. PMID- 26146682 TI - Animal biodiversity: An outline of higher-level classification and survey of taxonomic richness (Addenda 2013). AB - The kingdom Animalia is here estimated to have a total of 1,659,420 described species (including 133,692 fossil species) in 40 phyla. Among these, the most successful phylum Arthropoda alone represents 1,302,809 species, or about 78.5% of the total. The second largest phylum, Mollusca (118,061 species), is <10% of Arthropoda in diversity, but it is still much more diverse than other successful invertebrate phyla Platyhelminthes (29,488 species), Nematoda (25,043 species), Echinodermata (20,550 species), Annelida (17,426 species), Cnidaria (16,363 species), Bryozoa (11,474 species) and Porifera (10,876 species). The phylum Craniata, including the vertebrates, represents 85,432 species (including 19,974 fossil species): among these, 35,644 species of "fishes", 7,171 species of amphibians, 15,507 species of reptiles, 11,087 species of birds, and 16,014 species of mammals. PMID- 26146683 TI - Morphological and taxonomic revision of species of Squatina from the Southwestern Atlantic Ocean (Chondrichthyes: Squatiniformes: Squatinidae). AB - The morphology and taxonomy of species of Squatina from the southwestern Atlantic Ocean are revised. Species previously considered valid, Squatina argentina (Marini, 1930), Squatina guggenheim Marini, 1936 and Squatina occulta Vooren and da Silva, 1991, are investigated and described in detail, including a morphometric and meristic study of specimens from their recorded range. The taxonomic status of the doubtful nominal species Squatina punctata Marini, 1936 was also evaluated. This species was previously considered a junior synonym of S. argentina, a junior synonym of S. guggenheim, or a senior synonym of S. occulta. Although there is much morphological similarity between Squatina species, significant differences in dermal denticle patterns, dorsal coloration, tooth formula, and size at maturity are reported, enabling the recognition of S. argentina, S. guggenheim and S. occulta as valid species, and relegating S. punctata to the synonymy of S. guggenheim. Differences in skeletal morphology between valid species are described and considered supportive of the taxonomic hypothesis, corroborating a previous study of neurocrania. Additionally, an unidentified specimen is reported, as Squatina sp., from the continental shelf of Bahia state, Brazil, recognized by having more vertebral centra and a conspicuous dermal denticle morphology on interspiracular region, features not present in other South America angelshark species. A report on the only known syntype of Squatina dumeril Le Sueur, 1818 is presented, describing features that are still preserved and designating it as lectotype. Lateral-line sensory canals, skeleton, and cranial and hypobranchial muscles for the three valid species of Squatina from the southwestern Atlantic, as well as the brain and cranial nerves of S. guggenheim, are described and illustrated. PMID- 26146684 TI - Diversity of Southern Ocean deep-sea benthos between cosmopolitism and cryptic speciation: new species from the ANDEEP expeditions. AB - The richness of life in parts of the earth that to us appear inhospitable and remote never fails to fascinate scientists and non-scientists alike. The largest ecosystem of the planet, the abyssal plains of the world ocean, makes up about 90 percent of the seafloor and thus nearly 78 percent of the Earth's surface, yet only a minor fraction of this huge environment has been investigated. Authors have questioned repeatedly "how many species would live on earth and in the ocean" (Mora et al. 2011; May 2011), and recent estimations predict ~ 8.7 million (+/- 1.3 million SE) eukaryotic species globally, with 2.2 million of these being marine (Mora et al. 2011). To date, 91 % of all marine species still await description. Other authors concluded that marine biodiversity is grossly underestimated (Bouchet 2006) because so far, only one-third of all species descriptions concerns marine biota (Reaka-Kudla 1997; Groombridge & Jenkins 2000, Grassle 2001, Boltovskoy et al. 2005). We know that marine live thrives even in hadal trenches (Jamieson et al. 2009), that biogeographic ranges in the deep sea are dynamic (McClain & Mincks Hardy 2010) and that the origin of the modern deep sea fauna is ancient (Thuy et al. 2012). For example, the origin of Isopoda dates back to Permo-Triassic times (232- 314 mya; Lins et al. 2012). PMID- 26146685 TI - Preface. Cell fusion. PMID- 26146686 TI - The genus Hybos Meigen (Diptera: Empidoidea: Hybotidae) in Thailand. AB - The genus Hybos Meigen in Thailand is revised and full descriptions and keys provided for all 41 species. Thirty-four new species are recognized: H. aceriformis sp. nov., H. ancyclochiles sp. nov., H. anisoserratus sp. nov., H. bispinatus sp. nov., H. chaweewani sp. nov., H. daugeroni sp. nov., H. divisus sp. nov., H. grootaerti sp. nov., H. hylobates sp. nov., H. inthanonensis sp. nov., H. kaluang sp. nov., H. khamfui sp. nov., H. konkaogwang sp. nov., H. lannaensis sp. nov., H. mangraii sp. nov., H. meeamnat sp. nov., H. men sp. nov., H. merzi sp. nov., H. ngachang sp. nov., H. paknok sp. nov., H. phahompokensis sp. nov., H. pisadaanus sp. nov., H. saenmueangmai sp. nov., H. shamshevi sp. nov., H. sinclairi sp. nov., H. songbai sp. nov., H. steatopygus sp. nov., H. stigmaticus sp. nov., H. subapicalis sp. nov., H. tetricus sp. nov., H. thaosaeo sp. nov., H. thepkaisoni sp. nov., H. tilokarati sp. nov., H. yungyak sp. nov. Seven species known previously from China are recognized: H. ancistroides Yang & Yang, H. apicihamatus Yang & Yang, H. longus Yang & Yang, H. particularis Yang, Yang & Hu, H. serratus Yang & Yang, H. xishuangbannaensis Yang & Yang, and H. zhejiangensis Yang & Yang. Eight informal species-groups are tentatively proposed based on characters of male and female terminalia and attention is drawn to the many previously overlooked taxonomically useful characters of the female terminalia. Distribution maps of all species are presented and distributions categorised as 'widespread', 'eastern', 'southern', north-eastern' or 'northern and western'. Species richness and endemicity are greatest in mid to high elevation evergreen forest biotopes of the northern mountains and areas of endemism are identified on the Luang Prabang, Daen Lao, Thanon Thong-chai ranges and on the Isaan Plateau at least. Adult phenology is correlated with the rainy season in many species and preliminary analyses reveal that many high-elevation species have short emergence periods and restricted distributions, whereas some lowland species have longer emergence periods and wider distributions. PMID- 26146687 TI - Eriophyoid mites from Northeast China (Acari: Eriophyoidea). AB - We describe and illustrate herein one new genus and eighteen new eriophyoid mite species (Acari: Eriophyoidea) collected in northeast China. They are: Shevtchenkella huzhongiensis sp. nov. on Ulmus davidiana Planch. var. japonica (Sarg. ex Rehder) Nakai (Ulmaceae), Shevtchenkella jingboicus sp. nov. on Acer sp. (Aceraceae), Calepitrimerus flexuosus sp. nov. on Spiraea flexuosa Fisch. ex Cambess. (Rosaceae), Calepitrimerus maximowiczii sp. nov. on Crataegus maximowiczii Schneid. (Rosaceae), Calepitrimerus pilosus sp. nov. on Agrimonia pilosa Ledeb. (Rosaceae), Calepitrimerus yichunensis sp. nov. on Sorbaria sorbifolia (L.) A.Br. (Rosaceae), Cupacarus oxyphyllus sp. nov. on Euonymus oxyphyllus Miq. (Cel-astraceae), Epitrimerus sambucus sp. nov. on Sambucus williamsii Hance (Caprifoliaceae), Epitrimerus wuyingensis sp. nov. on Acer sp. (Aceraceae), Longisolenidionus amurensis gen. nov & sp. nov. on Tilia amurensis Rupr. (Tiliaceae), Phyllocoptes jiagedaqiensis sp. nov. on Cunninghamia sp. (Taxodiaceae), Aculops huzhongensis sp. nov. on Salix sp. (Sali-caceae), Aculus huzhongsalixus sp. nov. on Salix sp. (Salicaceae), Tetra angelica sp. nov. on Angelica sp. (Apiaceae), Tetra jiagedaqia sp. nov. on Lespedeza sp. (Fabaceae), Vittacus mandshurica sp. nov. on Corylus sieboldiana Blume var. mandshurica (Maxim.) C. K. Schneid. (Betulaceae), Vittacus cannabus sp. nov. on Cannabis sativa L. (Moraceae), and Peralox dentatis sp. nov. on Ulmus sp. (Ulmaceae). Two species formerly assigned to Rhyncaphytoptus, R. abiesis (Xue, Song & Hong, 2006) and R. fabris (Xue, Song & Hong, 2006) were reassigned to Nalepella, based on the presence of seta vi on the apical shield, and other characteristics of Nalepella. One species formerly assigned to Rhyncaphytoptus, R. fargesis (Xue, Song & Hong, 2006) was reassigned to Pentaporca, based on the presence of seta vi on the apical shield, opisthosoma with five ridges and other characteristics of Pentaporca. At the same time, four new eriophyoid mite records from China are provided, Acaphyllisa distasa (Keifer, 1961) rec. nov. on Betula costata Trautv. (Betulaceae), Shevtchenkella ulmi (Farkas, 1960) rec. nov. on Ulmus sp. (Ulmaceae), Calepitrimerus cariniferus Keifer, 1938, rec. nov. on Artemisia argyi H. Lev. & Vaniot (Asteraceae), Aculodes dubius (Nalepa, 1891) species complex, rec. nov. on Roegneria sp. (Poaceae). With this publication, the number of eriophyoid mite species in the region reaches 101. A list of these eriophyoid mites is provided. PMID- 26146688 TI - Taxonomic notes on the spider genus Messapus Simon, 1898 (Araneae, Corinnidae), with the description of the new genera Copuetta and Wasaka and the first cladistic analysis of Afrotropical Castianeirinae. AB - The Afrotropical sac spider genus Messapus Simon, 1898, presently placed in the Castianeirinae, is reviewed. The type material of the type species, M. martini Simon, 1898, clearly represents two different species, a corinnine female (here designated the lectotype) and a castianeirine male (the paralectotype). The female is redescribed and its corresponding male is described for the first time. As a result, Messapus is transferred to the Corinninae. Corinna natalis Pocock, 1898 is transferred to Messapus, while Messapus secundus Strand, 1907 is transferred to Merenius Simon, 1909. The new genus Copuetta gen. nov., with the type species C. maputa sp. nov., is established to accommodate the misidentified castianeirine male paralectotype of M. martini, and its matching female is described for the first time. Castianeira kibonotensis Lessert, 1921 syn. nov. is considered a junior synonym of Copuetta lacustris (Strand, 1916) comb. nov., which is redescribed from both sexes and transferred from Copa Simon, 1885. A further eleven new species of Copuetta are described: C. comorica sp. nov., C. erecta sp. nov., C. kakamega sp. nov., C. kwamgumi sp. nov., C. lesnei sp. nov., C. litipo sp. nov., C. lotzi sp. nov., C. magna sp. nov., C. naja sp. nov., C. uzungwa sp. nov. and C. wagneri sp. nov. Of these species, only C. lacustris and C. magna sp. nov. have large distribution ranges. Seven of the species are only known from the type locality and the remaining four have distributions restricted to one or two countries. A second new genus, Wasaka gen. nov., is described for four new species with restricted distributions from East and Central Africa: W. imitatrix sp. nov., W. montana sp. nov., W. occulta sp. nov. (type species) and W. ventralis sp. nov. A first phylogenetic analysis focused on the Afrotropical Castianeirinae is presented. The results support the placement and transfer of Messapus (including M. natalis comb. nov.) and Medmassa Simon, 1887 in the Corinninae, and the monophyly of a clade including the four cryptic lycosiform castianeirine genera from the Afrotropical Region (Copa, Copuetta gen. nov., Echinax Deeleman-Reinhold, 2001 and Wasaka gen. nov.). The implications of the phylogenetic results are briefly discussed. PMID- 26146689 TI - Ten new Gammarus species (Crustacea: Amphipoda: Gammaridae) from Yunnan-Guizhou Plateau, China. AB - Ten new species of the genus Gammarus are described from Yunnan-Guizhou Plateau, Southwest China, including Gammarus amabilis sp. nov., G. citatus sp. nov., G. echinatus sp. nov., G. egregius sp. nov., G. eliquatus sp. nov., G. hirtellussp. nov., G. margcomosus sp. nov., G. rivalis sp. nov., G. silendus sp. nov. and G. tranquillus sp. nov. Four of them are stygobite and with no eyes. Detailed illustrations and comparisons with related species are presented. A key to all species from Yunnan-Guizhou Plateau are given. PMID- 26146690 TI - Diagnoses and discussion of the group 1 and 2 Brazilian species of Heteragrion, with descriptions of four new species (Odonata: Megapodagrionidae). AB - Heteragrion is the most speciose and complex genus of neotropical Megapodagrionidae, with 47 species and one subspecies, and many of them are poorly defined. To improve the knowledge of the Brazilian species of the genus, 179 specimens of 13 of the 17 described species were examined. Four new species are described in tribute to the 40 thanniversary of the rock band Queen: Heteragrion freddiemercuryi (Holotype: Peruibe (24o 22' 48" S & 47o 04' 40" W-10 m), Sao Paulo State-09-III-2000); H. brianmayi (Holotype and allotype: Parque Estadual da Serra do Mar-Nucleo Caraguatatuba, Caraguatatuba (23o 35' 36" S & 45o 25' 07" W-61 m), Sao Paulo State-05-II-2000 and 10-III-2002); H. rogertaylori (Holotype and allotype: Fazenda Trabiju, Pindamonhangaba (22o 50' 40" S & 45o 31' 01" W-651 m), Sao Paulo State-26-III-1999); and H. johndeaconi (Holotype and allotype: Alto Paraiso de Goias (14o 10' 55" S & 47o 38' 36" W-1198 m), Goias State-18-VI-2008 and 17-VI-2008), holotypes, allotypes and most paratypes deposited in FAAL.Diagnostic illustrations of all species studied are provided. Color photographs of live individuals of H. brianmayi, H. aurantiacum, H. consors, H. mantiqueirae, H. tiradentense and H. triangulare are also presented. PMID- 26146691 TI - A revision of Afrotropical Quasimodo flies (Diptera: Schizophora; Curtonotidae). Part IV-the continental Afrotropical species of Curtonotum Macquart, with descriptions of thirteen new species and a combined phylogenetic analysis of the Curtonotidae. AB - A first comprehensive phylogeny of the entire family Curtonotidae is generated from molecular markers and morphology. The molecular data set comprises 33 taxa (30 in-group Curtonotidae; three out-groups: Camilla, Diastata, Drosophila) and 4 gene regions from 3 genes: 2 non-contiguous fragments from the CPSase (carbamoylphosphate synthetase) domain of the nuclear protein coding gene CAD (= CAD1 and CAD3); a fragment from the coding region of TPI (triosephosophate isomerase); and a fragment of the mitochondrial gene CO1 (cytochrome oxidase 1). We performed Bayesian like-lihood analyses in the program MrBayes 3.2; maximum likelihood analyses in the program Garli 2.0; and parsimony analysis in TNT on the concatenated genetic dataset. A data matrix of 62 discrete, morphological features of imagines was compiled from 75 taxa (70 in-group Curtonotidae taxa and five out-group exemplars: Amiota, Camilla, Diastata, Drosophila, Stegana), and these data are presented as Appendix II. For the combined morphological and molecular data a Bayes-ian likelihood analysis in the program MrBayes 3.2 and a parsimony analysis in TNT were performed, and for the morphological dataset a parsimony analysis was carried out in TNT. Results of the molecular and morphological analyses attest to the monophyly of the Curtonotidae and clearly indicate two primary clades, with Axinota + Curtonotum being sister to the remainder of the Curtonotidae. Curtonotum sensu stricto (sensu Klymko and Marshall 2011) is here adopted and ten newly-defined species-groups of the genus Curtonotum are recognised the: anus; boeny; campsiphallum; gonzo; platyphallum; rinhatinana; saheliense; striatifrons; stuckenbergi; and uncinatum species groups. The following nomenclatorial changes are proposed: Cyrtona appendiculata Seguy, 1938 is formally reinstated as a valid species and is re-moved as a junior synonym of Cyrtona pictipennis (Thomson, 1869). The former variety name sublineata (Duda, 1939) is upgraded to a specific name, as Parapsinota sublineata (Duda, 1939). The continental Afrotropical fauna of the genus Curtonotum Macquart, 1844 is revised and a diagnosis of the genus is provided. Known biology, behaviour and published information on immature stages of the genus are briefly reviewed. Type material of 12 of the 13 named species (C. angolense Tsacas, C. campsiphallum Tsacas, C. cuthbertsoni Duda, C. herrero Tsacas, C. pauliani Tsacas, C. platyphallum Tsacas, C. quinquevittatum Curran, C. saheliense Tsacas, C. sao Tsacas, C. simile Tsacas, C. striatifrons Malloch and C. tigrinum Seguy), was studied and errors in previous interpretations and designation of type specimens are resolved. Curtonotum pauliani is the only species occurring on both the continental African mainland and Madagascar. The type spec-imen of C. maculiventris (Enderlein) is lost and a neotype is here designated. One species synonymy is proposed: C. tigrinum Seguy, 1933 = C. maculiventris (Enderlein, 1917), syn. n. Additional material of the aforementioned species is noted, substantially increasing their known distributions. Thirteen species are described as new, namely: C. bicuspis Kirk- Spriggs, sp. n., C. cimbebas Kirk Spriggs, sp. n., C. constance Kirk-Spriggs, sp. n., C. freidberg Kirk-Spriggs, sp. n., C. gonzo Kirk-Spriggs, sp. n., C. hay Kirk-Spriggs, sp. n., C. litoralis Kirk-Spriggs, sp. n., C. marriott Kirk-Spriggs, sp. n., C. mcgregor Kirk-Spriggs, sp. n., C. moffatt Kirk-Spriggs, sp. n., C. tsacas Kirk-Spriggs, sp. n., C. uncinatum Kirk- Spriggs, sp. n. and C. unicuspis Kirk-Spriggs, sp. n. The head and thorax, frons, wing, fifth sternite and hypandrium of the male of the 25 named species are illustrated for the first time, as well as the highly diagnostic male phallus, from both the right and left sides laterally. A key to species based on male characters is provided, and species distributions are mapped and interpreted according to major vegetation types, topography and humidity zones. The biogeographical signif-icance of the continental Afrotropical species is discussed. Co-ordinates used to plot maps and a list of Major Habitat Types and Vegetation Types in which species occur are provided as Appendix III. PMID- 26146692 TI - A Volume Celebrating the Life of Don Colless, Australian Dipterist 1922-2012. AB - Donald Henry Colless (24 August 1922-16 February 2012) was a taxonomist at the Australian National Insect Collection (ANIC) from 1960 until his retirement in 1987. He continued working in ANIC as an Honorary Fellow until his death in 2012. Don's main scientific interests were in the taxonomy and biology of true flies, and in the theory of phylogenetic reconstruction and classification. Don was trained in entomology at the University of Sydney, and spent nearly two decades of his early career in Asia studying mosquitoes and disease transmission, first in the Army during the Second World War in New Guinea and Borneo (1942-45), then after the war in North Borneo (1947-1952) and as a lecturer in the Department of Parasitology at the University of Malaya (1952-1960) in Singapore. We list the 127 scientific papers and book chapters that Don published during his scientific career that spanned 64 years. Six of these papers were published in the prestigious international journal Nature, and he was Chief Curator of the ANIC from 1971-1977. Don had extremely broad taxonomic interests, publishing on the taxonomy of 18 families of Diptera that spanned the phylogenetic breadth of the order. He described as new to science the fly families Perissommatidae and Axiniidae, thirteen new genera and over 120 species and, with David McAlpine, authored the Diptera chapters in both editions of The Insects of Australia (Melbourne University Press, 1970 and 1991). He published a number of influential critiques of cladistic theory in the 1960's and 1970's, and advocated a phenetic approach to the discovery of taxonomic groups, and phylogenetic reconstruction. PMID- 26146693 TI - A taxonomic catalogue of the Dyspnoi Hansen and Sorensen, 1904 (Arachnida: Opiliones). AB - An update of the systematics and determination key of the Opiliones suborder Dyspnoi is provided. The included catalogue represents the first comprehensive species and synonymy listing since Roewer (1923). It summarises all taxonomic changes to date and attempts to be a sound basis against the exponential growing number of online errors, for which examples are given. Species taxonomy features most obvious changes within the Nemastomatidae. The number of species in the collective genus Nemastoma is reduced from 96 (Hallan 2005) to its sensu stricto definition of 7, and the excluded names are transferred to other genera or considered as nomina dubia, predominantly in Paranemastoma. The systematics of the superfamily Ischyropsalidoidea is discussed and family-level diagnoses are renewed to support taxonomical changes: The morphological heterogeneity in the Sabaconidae is resolved by reverting the family to its original monogeneric state. Taracus and Hesperonemastoma are separated as Taracidae fam. n., and Crosbycus is tentatively transferred to this assembly. The remaining genera of Ceratolasmatidae, Acuclavella and Ceratolasma, are included as subfamily Ceratolasmatinae in the Ischyropsalididae and Ischyropsalis is assigned subfamily status, respectively. Other nomenclatural acts are restricted to species-group level with the following synonymies established: Sabacon jonesi Goodnight & Goodnight, 1942 syn. n. (=cavicolens (Packard, 1884)), Dicranolasma diomedeum Kulczynski, 1907 syn. n. (=hirtum Loman, 1894), Mitostoma (Mitostoma) sketi Hadzi, 1973a syn. n. (=chrysomelas (Hermann, 1804)), Mitostoma asturicum Roewer, 1951 syn. n. (=pyrenaeum (Simon, 1879a)), Nemastoma formosum Roewer, 1951 syn. n. (=Nemastomella bacillifera bacillifera (Simon, 1879a)), Nemastoma reimoseri Roewer, 1951 syn. n. (=Paranemastoma bicuspidatum (C.L. Koch, 1835)), Nemastoma tunetanum Roewer, 1951 syn. n. (=Paranemastoma bureschi (Roewer, 1926)), Phalangium flavimanum C.L. Koch, 1835 syn. n. (=Paranemastoma quadripunctatum (Perty, 1833)), Crosbycus graecus Giltay, 1932 syn. n. (=Paranemastoma simplex (Giltay, 1932)), Nemastoma bimaculosum Roewer 1951 syn. n. (=Paranemastoma titaniacum (Roewer, 1914)), Trogulocratus tunetanus Roewer, 1950 syn. n. (=Calathocratus africanus (Lucas, 1849)), Trogulus albicerus So-rensen, 1873 syn. n. (=Calathocratus sinuosus (Sorensen, 1873)), Metopoctea exarata Simon, 1879a syn. n. (=Trogulus aquaticus Simon, 1879a), Trogulus galasensis Avram, 1971 syn. n. (=Trogulus nepaeformis (Scopoli, 1763)) and Trogulus roeweri Avram, 1971 syn. n. (=Trogulus nepaeformis (Scopoli, 1763)). Paranemastoma werneri (Kulczynski, 1903) is elevated from subspecies to species. Ischyropsalis luteipes Simon, 1872b is proposed as nomen protectum, taking precedence over Lhermia spinipes Lucas 1866 nomen oblitum. The same accounts for Anelasmocephalus cambridgei (Westwood, 1874) nomen protectum, taking precedence over Trogulus violaceus Gervais, 1844 nomen oblitum, Trogulus closanicus Avram, 1971 nomen protectum over Trogulus asperatus C.L. Koch, 1839a nomen oblitum, as well as Trogu-lus martensi Chemini, 1983 nomen protectum over Trogulus tuberculatus Canestrini, 1874 nomen oblitum. New combinations, all from Nemastoma, are Histricostoma anatolicum (Roewer, 1962), Mediostoma globuliferum (L. Koch, 1867), Nemastomella hankiewiczii (Kulczynski, 1909), Nemastomella maarebense (Simon, 1913), Nemastomella monchiquense (Kraus, 1961) and Paranemastoma simplex (Giltay, 1932); from Mitostoma: Nemastomella armatissima (Roewer, 1962). Revived combinations are Nemastomella cristinae (Rambla, 1969) (from Nemastoma) and Nemastomella sexmucronatum (Simon, 1911) (from Nemastoma). The following Nemastoma are transferred to Paranemastoma but suggested as nomina dubia: aeginum (Roewer, 1951), amuelleri (Roewer, 1951), bolei (Hadzi, 1973a), caporiaccoi (Roewer, 1951), carneluttii (Hadzi, 1973a), ferkeri (Roewer, 1951), gigas montenegrinum (Nosek, 1904), gostivarense (Hadzi, 1973a), ikarium (Roewer, 1951), quadripunctatum ios (Roewer, 1917), kaestneri (Roewer, 1951), longipalpatum (Roewer, 1951), macedonicum (Hadzi, 1973a), multisignatum (Hadzi, 1973a), nigrum (Hadzi, 1973a), perfugium (Roewer, 1951), santorinum (Roewer, 1951), senussium (Roewer, 1951), sketi (Hadzi, 1973a), spinosulum (L. Koch, 1869). Further suggested nomina dubia are Trogulus coreiformis C.L. Koch, 1839a, Trogulus lygaeiformis C.L. Koch, 1839a and Trogulus templetonii Westwood, 1833. PMID- 26146694 TI - Review of the genus Thrips and related genera (Thysanoptera, Thripidae) from Japan. AB - Members of Thrips genus-group from Japan are reviewed, and 45 species in seven genera are recognized. Nine species and one genus are newly described: Stenchaetothrips amamiensis sp. n., S. dentatus sp. n., S. pleioblasti sp. n., Thrips nonakai sp. n., T. ogasawarensis sp. n., T. shiranesanus sp. n., T. syringae sp. n., T. typicus sp. n. and Tsutsumiothrips ryukyuensis gen. et sp. n. Moreover, 14 species of two genera are newly recorded from Japan: S. langkawiensis Ng & Mound, S. undatus Wang, Thrips alni Uzel, T. aspinus Mound & Masumoto, T. brevicornis Priesner, T. brunneus Ishida, T. extensicornis Priesner, T. minutissimus Linnaeus, T. pini (Uzel), T. subnudula (Karny), T. sukki Bhatti & Lee, T. trehernei Priesner, T. urticae Fabricius and T. vitticornis Karny. A previously recorded species, Stenchaetothrips bambusae (Shumsher) is excluded from the Japanese fauna. PMID- 26146695 TI - Letter: IgG4-hepatopathy and IgG4-associated autoimmune hepatitis. PMID- 26146696 TI - Catalogue of the Krantz Brachiopod Collection at the Science Museum of the University of Coimbra (Portugal). AB - The specimens of the Krantz Brachiopod Collection of the Science Museum of the University of Coimbra (Portugal) are revised according to modern taxonomy and presented in systematic order according to inventory number, type species, figured representative and, as far as possible, detailed information regarding stratigraphy and collecting localities. The collection itself contains 170 lots yielding 474 specimens and representing 15 of the 27 brachiopod orders. The material comes from Europe, Russia, and the United States and represents all Palaeozoic and Mesozoic periods; the majority of the brachiopods are from the Devonian of Germany, mostly collected in classical outcrops from the Rhenish Slate Mountains, many of which are no longer accessible. PMID- 26146697 TI - Letter: TIPSS in hepatocellular carcinoma. PMID- 26146698 TI - New littoral, shelf, and bathyal Paratanaidae (Crustacea: Peracarida: Tanaidacea) from New Zealand, with descriptions of three new genera. AB - Three new genera, Acallocheirus, Aparatanais, and Penteparatanais, and seven new species of the paratanaid subfamily Paratanaidinae are described from New Zealand. New records of three previously known species Atemtanais taikaha, Paratanais paraoa, and P. tara, are also given. Paratanais denticulatus, P. intermedius, P. malignus, P. spinanotandus,and P. vicentetis are transferred to Aparatanais. A key is given to all paratanaidin genera and the NZ Paratanais species. In NZ waters, paratanaids are now known from the littoral zone to 908 m in the bathyal regions of the Chatham Rise and Hikurangi Margin, several of the offshore species being recorded in bryozoan mats. All but one appear to be endemic but may have sibling species elsewhere, particularly in the Southern Hemisphere. Supplementary notes are given on two Australian species P. maleficus and P. perturbatius that clarify their description and diagnostic characters. PMID- 26146699 TI - The stone huntsman spider genus Eusparassus (Araneae: Sparassidae): systematics and zoogeography with revision of the African and Arabian species. AB - An overview on the systematics of the stone huntsman spider genus Eusparassus Simon, 1903 and an identification key to the known species are presented. Six species-groups are proposed: the walckenaeri group (3 species, Eastern Mediterranean to Arabia and parts of North-Eastern Africa), dufouri group (8 species, Iberian Peninsula to parts of North-western Africa), vestigator group (3 species, Central to Eastern Africa and an isolated area in India), jaegeri group (4 species, Southern and South-Eastern Africa), tuckeri group (2 species, South Western Africa) and doriae group (7 species, Middle East to Central and South Asia). Two species, E. pontii Caporiacco, 1935 and E. xerxes (Pocock, 1901) could not be placed in any of the above groups. The species from Africa and Arabia are revised. The following ten species are re-described: Eusparassus barbarus (Lucas, 1846), E. atlanticus Simon, 1909 stat. nov., E. syrticus Simon, 1909, E. oraniensis (Lucas, 1846), E. letourneuxi (Simon, 1874), E. fritschi (Koch, 1873) stat. rev., E. walckenaeri (Audouin, 1826), E. vestigator (Simon, 1897) comb. nov., E. laevatus (Simon, 1897) comb. nov. and E. tuckeri (Lawrence, 1927) comb. nov. The latter three species are transferred from Olios Walckenaer, 1837. Seven new species are described: Eusparassus arabicus spec. nov. (male, female) from Arabian Peninsula, E. educatus spec. nov. (male, female) from Namibia, E. reverentia spec. nov. (male, female) from Burkina Faso and Nigeria, E. jaegeri spec. nov. (male, female) from South Africa and Botswana, E. jocquei spec. nov. (male, female) from Zimbabwe, E. borakalalo spec. nov. (female) from South Africa and E. schoem-anae spec. nov. (male, female) from South Africa and Namibia. Three taxa, E. dufouri maximus Strand, 1906 syn. nov., E. rufobrunneus Caporiacco, 1941 syn. nov. and Olios furcatus Lawrence, 1927 syn. nov. are proposed as junior syn onyms of E. oraniensis, E. vestigator comb. nov. and E. tuckeri comb. nov. respectively. Males of E. atlanticus stat. nov. and E. fritschi stat. rev. are described for the first time as in the female of E. vestigator comb. nov. Neotypes are desig-nated for E. barbarus, E. oraniensis and E. letourneuxi (all from Algeria). The male and female of Cercetius perezi Simon, 1902, which was known only from the immature holotype, are described here for the first time. This resulted in recogniz-ing the monotypic and little used generic name Cercetius Simon, 1902 as a synonym of the widely used name Eusparas-sus. Nearly all the species are illustrated for the first time. Eusparassus concolor Caporiacco, 1939 is transferred to Olios and the replacement name Olios quesitio is proposed because of secondary homonymy. For the majority of the species, new geographical records are presented. The systematics and zoogeography of the currently known species and species groups are discussed. A brief note on the copulation process of E. walckenaeri is presented. PMID- 26146700 TI - Taxonomic revision of the spider genera Agyneta and Tennesseellum (Araneae, Linyphiidae) of North America north of Mexico with a study of the embolic division within Micronetinae sensu Saaristo & Tanasevitch 1996. AB - The genera Agyneta Hull 1911 and Tennesseellum Petrunkevitch 1925 are revised for North America north of Mexico. The synonymy of Meioneta Hull 1920 with Agyneta Hull 1911 proposed by Saaristo 1973 is corroborated. The North American fauna north of Mexico of Agyneta now includes a total of 69 species, of which 31 are new species: A. watertoni n. sp., A. perspicua n. sp., A. aquila n. sp., A. yukona n. sp., A. darrelli n. sp., A. bucklei n. sp., A. erinacea n. sp., A. crawfordi n. sp., A. vinki n. sp., A. panthera n. sp., A. miniata n. sp., A. danielbelangeri n. sp., A. pistrix n. sp., A. flax n. sp., A. barfoot n. sp., A. sandia n. sp., A. spicula n. sp., A. grandcanyon n. sp., A. chiricahua n. sp., A. crista n. sp., A. tuberculata n. sp., A. catalina n. sp., A. ledfordi n. sp., A. platnicki n. sp., A. bronx n. sp., A. paquini n. sp., A. girardi n. sp., A. flibuscrocus n. sp., A. delphina n. sp., A. okefenokee n. sp. and A. issaqueena n. sp. The genus Tennesseellum includes two spe-cies, with one new species, T. gollum n. sp. Ten new synonyms are recognized: Meioneta grayi Barnes 1953 = Anibontes mimus Chamberlin 1924; Meioneta dactylata Chamberlin & Ivie 1944, Meioneta officiosa (Barrows 1940) = Meioneta micaria (Emerton 1882); Meioneta imitata Chamberlin & Ivie 1944 = Meioneta leucophora Chamberlin & Ivie 1944; Meioneta ferosa (Chamberlin & Ivie 1943) = Meioneta fillmorana (Chamberlin 1919); Meioneta fuscipes Chamberlin & Ivie 1944 = Meioneta floridana (Banks 1896); Meioneta alaskensis Holm 1960 = Meioneta maritima (Emerton 1919); Meioneta meridionalis (Crosby & Bishop 1936), Meioneta zebrina Chamberlin & Ivie, 1944 = Meioneta parva (Banks 1896); Meioneta zygia (Keyserling 1886) = Meioneta fabra (Keyserling 1886). Ten informal species groups are proposed based on the study on the male palpal conformation of the embolus and radical division; these groups are not intened to be phylogenetic hypotheses. The limits and composition of the subfamily Micronetinae sensu Saaristo & Tanasevitch 1996 are discussed. PMID- 26146701 TI - Review and analysis of information on the biology and morphology of immature stages of robber flies (Diptera: Asilidae). AB - Recent publications on the immature stages of robber flies (Asilidae) are reviewed and listed for the 14 currently recognized subfamilies (Asilinae, Bathypogoninae, Brachyrhopalinae, Dasypogoninae, Dioctriinae, Laphriinae, Leptogastrinae, Ommatiinae, Phellinae, Stenopogoninae, Stichopogoninae, Tillobromatinae, Trigonomiminae, and Willistonininae). For the Phellinae there are only limited data on the pupal cases, and for the Tillobromatinae there are only limited data on the eggs (potential oviposition site in soil) and pupal cases. The recent literature is compared with pertinent pre-1972 publications. PMID- 26146702 TI - Revision and reclassification of Lasioglossum (Evylaeus), L. (Hemihalictus) and L. (Sphecodogastra) in eastern North America (Hymenoptera: Apoidea: Halictidae). AB - The black species of weak-veined Lasioglossum (or Hemihalictus series) in eastern North America are revised to clarify their taxonomy and nomenclature and to facilitate identification. A subgeneric classification based upon available phylogenetic data is applied. Lasioglossum (Sphecodogastra) is applied more broadly than any previous usage to include many species typically classified as L. (Evylaeus). The subgenus L. (Evylaeus) is retained but applied narrowly in agreement with phylogenetic results. Lasioglossum (Hemihalictus) has historically been considered monotypic but is here applied to many species of L. (Dialictus) sensu lato (equivalent to the carinaless L. (Evylaeus) of some authors). Usage of L. (Dialictus) is restricted primarily to species with metallic integument. Additional subgeneric synonymies for extralimital taxa are formalized and discussed. Descriptions are provided for each species with a synonymic list, diagnosis, and notes on taxonomy and biology. The recently revised Onagraceae specialist species of L. (Sphecodogastra) are given abbreviated treatments. Notes on available DNA barcode data are given, with diagnostic characters supplied for closely related spe-cies. One new species is described: L. (Sphecodogastra) seillean Gibbs and Packer and the males of L. fedorense (Crawford) and L. pectinatum (Robertson) are described for the first time. The following three new synonymies are proposed: Lasioglossum (Hemihalictus) sopinci (Crawford), senior subjective synonym of Evylaeus bradleyi Mitchell; Lasioglosum (Hemihalictus) macoupinense (Robertson), senior subjective synonym of Halictus divergens Lovell; and Lasioglossum (Hemihalictus) inconditum (Cockerell), senior subjective synonym of Halictus tracyi Cockerell. Lasioglossum inconditum is here considered to be distinct from the Palaearctic species L. rufitarse (Zetterstedt). A lectotype is designat-ed for Halictus quebecensis Crawford. We present the first record of L. lustrans (Cockerell) and L. swenki (Crawford) in Canada and the first record of L. lusorium (Cresson) east of the Mississippi River. Updated keys to species are provided for the fauna of eastern North America. PMID- 26146703 TI - Checklist of the spiders (Araneae) of Israel. AB - This checklist records 631 spider species and subspecies belonging to 49 families in Israel. Species distributions are given in both generalised (by main geographic areas of the country) and detailed (by localities) form. Twenty-seven records are considered as doubtful and another ten are based on misidentifications. A historical survey is provided. Each record is presented in its original combination. The list is dominated by members of the families Gnaphosidae and Salticidae (20.0% and 17.1% of total species, respectively). The level of regional endemism exceeds 37.0%. PMID- 26146704 TI - On the arboreal acarofauna of Hungary: some new and rare species of prostigmatic mites (Acari: Prostigmata: Tydeidae, Iolinidae and Stigmaeidae). AB - Eleven arboreal prostigmatic mites from the families Tydeidae, Iolinidae and Stigmaeidae (Prostigmata) are recorded from Hungary. Among them, 8 species are new for science: Tydeus narolicatus Kazmierski and Ripka sp. nov., T. martae Kazmierski sp. nov., T clavimaculatus Kazmierski sp. nov., Lorryia hungarica Laniecka and Ripka sp. nov., L. sanctikingai Ripka and Laniecka sp. nov., L. bathorii Ripka and Kazmierski sp. nov., Neopronematus solani Laniecka and Kazmierski sp. nov., and Mediolata ronaldi Laniecka sp. nov. Neopronematus lundqvisti Sadeghi et al., 2012 is a new species for fauna of Hungary. PMID- 26146705 TI - On two Liphistius species (Araneae: Liphistiidae) from Laos. AB - Two mesothelid trapdoor spider species, Liphistius isan Schwendinger, 1998 and L. laoticus sp. n., are reported from southern Laos, east of the Mekong River. Liphistius isan was previously known only from the type locality in northeastern Thailand, and it is here also reported from a second Thai locality. Liphistius laoticus sp. n. is newly described from males and females. The two species belong to distinct lineages and they both have their closest relatives in northeastern Thailand. Information on biology and relationships of these two species is given. PMID- 26146706 TI - A new species of the genus Trichoformosomyia Townsend from Malaysia (Diptera: Tachinidae). AB - A new species of Trichoformosomyia, T. abbreviata sp. nov., is described from Sabah, Malaysia. Trichoformosomyia sauteri Baranov is redescribed and it is newly recorded from China, Vietnam and Japan. A key to the three known species of Trichoformosomyia is given and monophyly of the genus is briefly discussed based on adult morphology. PMID- 26146707 TI - Lycomimus, a new genus of Australian Ptilodactylidae (Coleoptera: Byrrhoidea). AB - A new genus of Ptilodactylidae, Lycomimus gen. n., based on L. bejsaki sp. n. from northern New South Wales and southern Queensland, Australia, is described. The genus is compared with other known ptilodactylid genera, and a key is provided to the genera occurring in Australia. PMID- 26146708 TI - Molecular approach to identify sibling species of the Ceriodaphnia cornuta complex (Cladocera: Daphniidae) from Australia with notes on the continental endemism of this group. AB - Taxonomy of the genus Ceriodaphnia Dana, 1853 (Cladocera: Daphniidae) has been uncertain for a long time, the species richness was often underestimated due to (1) a morphological similarity among the species and (2) their great morphological inter- and intra- populational variability. Support for this conclusion comes from the first analysis of three molecular markers for Australian representatives of this genus, two mitochondrial (COI and 16s) and one nuclear (28s) genes. Sequence analysis indicates the existence of three sibling Australian species belonging to the complex. Further work is required to establish species boundaries and investigate potential morphological diagnoses. Comparison of COI sequences with all other published sequences from the genus Ceriodaphnia revealed no common clades among continents pointing to the regional endemism within this group, which could suggest its Mesozoic differentiation. PMID- 26146709 TI - Two new peculiar species of Neotropical Brachypogon Kieffer (Diptera: Ceratopogonidae). AB - Brachypogon biradialis from southern Argentina and Chile and Brachypogon tico from Costa Rica, are described and illustrated from female specimens. They are provisionally placed in the genus Brachypogon although not exactly fitting in any of the already recognized subgenera of this genus. PMID- 26146710 TI - DNA barcoding confirms the presence of Hydria cervinalis (Scopoli, 1763) in the Iberian Peninsula (Lepidoptera: Geometridae: Larentiinae). PMID- 26146711 TI - Re-evaluating the taxonomic status of Chiromantis in Thailand using multiple lines of evidence (Amphibia: Anura: Rhacophoridae). AB - Because of general phenotypic similarities and distribution of species across two continents, the genus Chiromantis has proven somewhat enigmatic. Among Indochinese species, the validity of C. hansenae has been questioned by some who consider it a junior synonym of C. vittatus. We employ three lines of evidence to elucidate the taxonomic status and phylogenetic relationships of four congeneric species of Chiromantis frogs from Thailand. Results of molecular, morphological, and bioacoustic data analyses support at least four evolutionarily distinct and monophyletic clades: C. doriae, C. nongkhorensis, C. vittatus and C. hansenae. Genetic divergence between C. vittatus and C. hansenae is > 10%, significantly greater than C. doriae and C nongkhorensis (4.5%). Our results support the taxonomic validity of C. hansenae and suggest that there may be more diversity within C. hansenae and C. vittatus than is currently recognized. PMID- 26146712 TI - Eulasia (Rudeulasia) daccordii, a new species from southern Levant, with notes on E. pietschmanni Breit and E. baumanni Mitter (Coleoptera: Scarabaeoidea: Glaphyridae). AB - Eulasia daccordii new species is described from Jordan, West Bank, and Israel, where it is known from the Jordan Valley and the Negev. It was previously confused with E. pietschmanni Breit, to which it is very similar and from which it can be recognized mainly for the structure and distribution of the pronotal setae and the shape of the protibia of males. Remarks on distribution and colour range of E. pietschmanni Breit are provided, and its year of description is corrected from 1919 to 1920. In addition, taxonomic and diagnostic remarks on the poorly known sympatric species E. baumanni Mitter are presented: it is clarified that this poorly known taxon is related to E. papaveris (Sturm), whose Levantine populations require a taxonomic reassessment. PMID- 26146713 TI - The genus Corella (Ascidiacea, Phlebobranchia, Corellidae) in the Southern Hemisphere with description of a new species. AB - In the Southern Hemisphere the species attributed to Corella eumyota, Traustedt, 1882 are likely more varied than previously expected. This ascidian species was described from specimens collected at Valparaiso (Chile). Until now it was considered as a widely distributed species in the southern hemisphere. New collections from Chile and the Antarctic area have allowed to separate two species and re-establish Corella antarctica Sluiter, 1905 as a valid species (Alurralde 2013).A morphological re-examination of many specimens from the MNHN collections and especially recent surveys as CEAMARC and REVOLTA confirms that Antarctic specimens from the Antarctic Peninsula and Terre Adelie obviously differ from sub-Antarctic material more varied than previously estimated. On the other hand, C. eumyota invasive in Europe (Lambert 2004) has been shown to be the same as specimens from Chile, New Zealand and other sub-Antarctic regions. The present morphological study compares Corella from different regions and describes a new species Corella brewinae n. sp that is found living mixed with C. eumyota populations. PMID- 26146714 TI - The adults of Camelobaetidiusjanae Dominique & Thomas, 2001 and C. yacutinga Nieto, 2003, with a new synonym for C. leentvaari Demoulin, 1966 (Ephemeroptera: Baetidae). AB - The genus Camelobaetidius Demoulin, 1966 has 39 species distributed throughout the Nearctic and Neotropical Regions, being one of the most studied genera of the family Baetidae. Based on material from Brazil, the aim of the present paper is to describe adults of C. janae Dominique & Thomas, 2001 and C. yacutinga Nieto, 2003, and to recognize a new synonym for Camelobaetidius leentvaari Demoulin, 1966 (= C. mantis Traver & Edmunds, 1968 nov. syn.) based on the examination of type material. PMID- 26146715 TI - Sphyrna gilberti sp. nov., a new hammerhead shark (Carcharhiniformes, Sphyrnidae) from the western Atlantic Ocean. AB - Sphyrna gilberti sp. nov. is described based on 54 specimens collected in the coastal waters of South Carolina, U.S.A. Morphologically, S. gilberti sp. nov. is separable from S. lewini (Griffith & Smith 1834) only in the number of precaudal vertebrae. Due to rarity of specimens and the highly migratory behavior of most sphyrnids, the range of S. gilberti sp. nov. is unknown. PMID- 26146716 TI - Study on the genus Morulina (Collembola: Neanuridae) with description of a new species from Northwest China. AB - A new species of Morulina from China is described and illustrated. It is close to M. orientis Tanaka from Japan and M. himalayana Cassagnau from Nepal. There are 12 tubercles on the head of all three species, but they can be separated by a number of chaetotaxic characters. A key for identification of all the species in the genus is given. PMID- 26146717 TI - A new species of Cylindrostethus Mayr (Hemiptera, Gerromorpha, Gerridae) for the Neotropical Region, with an identification key for the species of Group 1 sensu Drake 1952. AB - A new species of Cylindrostethus Mayr, C. meloi sp. nov. is described and illustrated from the state of Amazonas, Brazil. This species can be easily distinguished from congeners by the shape of the proctiger. An identification key for the species of Group 1 sensu Drake 1952 is presented. PMID- 26146718 TI - Rediscovery of two rare ptilodontines in Taiwan: Himeropteryxyui Okano, 1969 stat. nov. and Ptilophora rufula Kobayashi, 1994 (Lepidoptera, Notodontidae). PMID- 26146719 TI - The advertisement call of the toad Rhinella humboldti (Bufonidae). PMID- 26146720 TI - Re-evaluation of characters in Apolemiidae (Siphonophora), with description of two new species from Monterey Bay, California. AB - Siphonophores are polymorphic planktonic marine Cnidarians. The family Apolemiidae is sister to all other species of physonect and calycophoran siphonophores. Although this enigmatic group arguably includes the longest animal species on the planet, their colony-level organization and growth patterns are not well understood. Here we describe two new apolemiid species: Apolemia lanosa sp. nov. and A. rubriversa sp. nov. We provide detailed descriptions of zooid budding and the organization of mature zooids within the siphosome. Our findings reveal that at least two distinct general patterns of siphosomal organization are found in different Apolemia species. In the first pattern, dispersed organization, zooids independently attach directly to the siphosomal stem. In the second pattern, pedunculate organization, only the gastrozooid is attached directly to the stem, and the other zooids of the cormidium branch from its peduncle. This diversity within Apolemia indicates that fundamental aspects of zooid budding and organization are homoplastic within Siphonophora, as both patterns are also found in other siphonophores. The observations presented here greatly clarify the interpretation of diagnostic characters within Apolemiidae, bear on the status of the three previously described species, provide critical detail for understanding the diversity of colony-level organization in siphonophores, and establish a foundation for the description of additional apolemiid species. PMID- 26146721 TI - A new species of Kukri Snake (Oligodon Fitzinger, 1826; Squamata: Colubridae) from the Cat Tien National Park, southern Vietnam. AB - We describe a new species of the genus Oligodon from the lowland forests of Cat Tien National Park, Dong Nai Province, in southern Vietnam. Oligodon cattienensis sp. nov. is distinguished from the remaining Southeast Asian kukri snakes by the combination of the following characters: medium-sized, deeply forked hemipenes without spines, 17-17-15 dorsal scale rows, nasal entire, 2 small postoculars, almost equal in size, 167-178 ventrals, 31-35 subcaudals, 24-35 + 5 large dark edged vertebral blotches in combination with a yellow-orange or red vertebral stripe between blotches, head pattern including ocular band, temporal bands and elongated chevron, ventrals pink or whitish (reddish in juveniles) in life, some bearing a quadrangular dark blotch on each lateral side, or ventrals being entirely dark. Based on the hemipenial morphology the new species is assigned to the Oligodon cyclurus species group. A comparison table for all Indochinese Oligodon is provided. PMID- 26146722 TI - Three new eriophyoid mite species in the tribe Phyllocoptini from Yunnan Province, southwestern China (Acari: Eriophyidae: Phyllocoptinae). AB - In this paper, three new Phyllocoptini eriophyoid mite species from Yunnan Province, China are described and illustrated: Proiectus rodgeseta sp. nov. on Pinus armandii Franch. (Pinaceae), Proiectus granularpro sp. nov. on Pinus tabuliformis Carr. (Pinaceae) and Phyllocoptrutajuniperiana sp. nov. on Juniperus chinensis Linn. (Cupressaceae). All are vagrants causing no apparent damage to their host plants. A key to the species of Proiectus is provided. PMID- 26146723 TI - Caesio xanthalytos, a new species of fusilier (Perciformes: Caesionidae) from the Western Indian Ocean, with records of range extensions for several species of Caesionidae. AB - Caesio xanthalytos, a new species of fusilier, closely related to Caesio caerulaurea Lacepede 1801, is described from several specimens from various localities on the east coast of Africa, and from southern Madagascar. While very similar in colour pattern to C. caerulaurea, its lateral line lies within a dominant, composite yellow stripe, whereas in C. caurulaurea the lateral line lies immediately below the yellow stripe. The two species also differ in the number of lateral-line scales, the modal number of pectoral-fin rays, in the form of the nuchal scale patch, and genetically. The new species has been observed to school with C. caerulaurea and with C. varilineata Carpenter 1987. The ranges of several species of Caesio and Pterocaesio and of Dipterygonotus balteatus and Gymnocaesio gymnoptera are extended to localities on the South African east coast. PMID- 26146724 TI - Four new species of the genus Pseudopoda Jager, 2000 (Araneae, Sparassidae) from Yunnan Province, China. AB - Four new species of the huntsman spider genus Pseudopoda Jager, 2000 are reported from Yunnan Province, China: Pseudopoda gibberosa sp. nov. (male, female), P. semiannulata sp. nov. (male, female), P. breviducta sp. nov. (male, female) and P. triangula sp. nov. (male, female). PMID- 26146725 TI - Diagnostic clues for identification of selected species of the Micropsectra atrofasciata group, with description of M. uva sp. nov. from Croatia (Diptera: Chironomidae: Tanytarsini). AB - Micropsectra uva sp. nov. is described from the Plitvice Lakes National Park (Croatia), and placed in the Micropsectra atrofasciata systematic species group. Morphological key structures/characters for adult males of the new species and several closest Micropsectra Kieffer are illustrated in detail and evaluated. PMID- 26146726 TI - Paleonura bilinskii (Collembola, Neanuridae, Paleonurini), a new species from Ecuador. PMID- 26146727 TI - Muscidae (Insecta: Diptera) of Argentina: revision of Buenos Aires province fauna, with a pictorial key to species. AB - The knowledge of Muscidae of Argentina is fragmentary and incomplete. In this work, 43 species of Muscidae are recorded from Buenos Aires province, the largest and the most populated of Argentina. Redescriptions of Dolichophaonia trigona (Shannon & Del Ponte), Helina nivaloides Albuquerque, Mydaea sexpunctata (Wulp) are presented. Two new synonymies are proposed: Mydaea latomensis Snyder is established as a new junior synonym of M sexpunctata, and Neodexiopsis croceafrons Snyder is established as a new junior synonym of N. paulistensis Albuquerque. We designated lectotypes for Ophyra carbonaria Shannon & Del Ponte, Phyronota platensis Shannon & Del Ponte, Phyronota portensis Shannon & Del Ponte, and Spilogaster sexpunctata Wulp. Arthurella choelensis Patitucci & Mariluis, Limnophora aurifacies Stein, Lispe setuligera (Stein), Morellia (Trichomorellia) trichops (Malloch), Neomuscina zosteris (Shannon & Del Ponte), and Synthesiomyia nudiseta (Wulp) are recorded for the first time from Buenos Aires province, and Graphomya maculata (Scopoli) and Helina nivaloides are newly recorded from Argentina. New records of distribution for 21 of the 43 species herein studied are presented. A pictoric key to adults of the 43 species of Muscidae from Buenos Aires province is presented. Notes on biology, distribution in Argentina, and references in the literature for this family are also given. PMID- 26146728 TI - Freshwater crabs from eastern Panama: a new species of Potamocarcinus H. Milne Edwards, 1853, and new records of two little-known species (Crustacea: Decapoda: Pseudothelphusidae, Trichodactylidae). AB - A small collection of freshwater crabs from eastern Panama revealed a new species of pseudothelphusid crab, Potamocarcinus darienensis n. sp., which is described and illustrated. The new species is characterized by an unusual arrangement of distal processes in the male first gonopod, in which the mesial lobe is folded in a latero-cephalic direction over the apex and the apex is broadened by a rounded protuberance in its caudo-lateral surface, the cephalic surface having a small, conical median cephalic process, and a large, prominent, subtriangular proximal cephalic process. New records of two little-known species described from eastern Panama, Spirocarcinus garthi (Pretzmann, 1971) (Pseudothelphusidae) and Melocarcinus meekei (Pretzmann, 1968) (Trichodactylidae), are listed and the first gonopod of S. garthi is redescribed. PMID- 26146729 TI - Two new species of Pseudonannolene Silvestri, 1895 from Brazilian limestone caves (Spirostreptida: Pseudonannolenidae): synotopy of a troglophilic and a troglobiotic species. AB - Pseudonannolene ambuatinga n. sp. and Pseudonannolene saguassu n. sp. are described from individuals collected in limestone caves in the municipality of Pains, Minas Gerais, Brazil, which comprises a scenario of great conflict between speleological preservation and limestone extraction. The two species differ in their gonopod morphology and in size and color. Pseudonannolene ambuatinga n. sp. is regarded as the second troglobite species known for the family. This is the first report for Brazil of syntopy in two congeneric species in the same cave. PMID- 26146730 TI - New species of Myrmekioderma (Demospongiae: Halichondrida: Heteroxyidae) from Brazil. AB - The genus Myrmekioderma comprises eight species widely distributed, two of which occur in the Western Atlantic. We describe here a new species of Myrmekioderma from Northeastern Brazil with a discussion on the taxonomy of the Brazilian species. Samples were collected by trawling in the continental shelf of Sergipe and Alagoas States. Myrmekioderma intrastrongyla sp. nov. has strongyles in the choanosome, a single category of acanthoxea and two categories of trichodragmata. Regarding the external morphology, the closest species of M intrastrongyla sp. nov. are Myrmekioderma rea and M granulatum. However, the former differs from the new species by possessing oxeas and styles and the last by its unique category of trichodragmata. Myrmekioderma rea was the only species that was recorded for Brazil, occurring in Maranhao and Rio Grande do Sul States, but both records need to be reassessed. PMID- 26146731 TI - New species of Calamoncosis Enderlein (Diptera: Chloropidae) from South Africa. AB - Three new and atypical species of Afrotropical Calamoncosis are described: Calamoncosis agricola sp. n. (type locality- South Africa: 15 km E Klaserie); Calamoncosis flavida sp. n. (type locality-South Africa: Roodewal); and Calamoncosis unicornis sp. n. (type locality-South Africa: 15 km E Klaserie). Calamoncosis unicornis exhibits extreme modification and sexual dimorphism in the antenna; in males the arista is reduced to a minute stub and the first flagellomere is greatly elongate and long setulose; in females the arista is well developed and the first flagellomere is somewhat elongate and pubescent. Calamoncosis agricola is unusual for the genus in that crossvein dm-cu is absent, and C. flavida has an enlarged, rounded first flagellomere. The combination of characters seen in these species expands the known range of morphological variation, and thus the generic limits, of Calamoncosis. Recognition of these new species more than doubles the known Afrotropical fauna of Calamoncosis, previously represented only by C. aenescens (Becker) and C. pauliani (Seguy). PMID- 26146732 TI - New replacement name for Angustella Li, 1986 (Hemiptera: Cicadellidae: Evacanthinae: Evacanthini), with description of a new species. AB - A new replacement name Angustuma nom. nov. is proposed for the leafhopper genus Angustella Li, 1986 of the subfamily Evacanthinae (Hemiptera: Cicadellidae), and twelve new combinations are proposed. A new species Angustuma rudorsuma sp. nov. is described and illustrated from China. A key is given to distinguish all species of the genus. The type specimens of the new species are deposited in the Institute of Entomology, Guizhou University, Guiyang, China (GUGC). PMID- 26146733 TI - Discovery of the genus Paraleuctra (Plecoptera: Leuctridae) from Palearctic China, with description of P. qilianshana sp. nov. AB - A new species of the genus Paraleuctra, P. qilianshana sp. nov., is described from Mt. Qilianshan, Gansu Province, China. The new species is the first representative of Paraleuctra discovered in the Palearctic Region of China. The new species is compared with its regional congeners. PMID- 26146734 TI - A new Permagrionidae from the Middle Permian of the South of France (Odonatoptera: Protozygoptera). AB - The new permagrionid protozygopteran genus and species Salagoulestes wesleyi is described from the Middle Permian of Lodeve Basin, Salagou Formation. It seems to be more closely related to the two genera Scytolestes and Permagrion than to any other Permagrionidae. It increases the diversity of the odonatopteran fauna in the Salagou Formation to 14 different species. PMID- 26146735 TI - Ten new species of Triclistus Forster, 1869 (Hymenoptera, Ichneumonidae) from Peru, with a key to Neotropical species. AB - Triclistus Forster, 1869 is a widely distributed genus of the family Ichneumonidae, rich in the Old World but poorly represented in the Neotropical region. Ten new species are described: Triclistus ashaninka sp. n., Triclistus bicolor sp. n., Triclistus castilloai sp. n., Triclistus cholo sp. n., Triclistus muqui sp. n., Triclistus inti sp. n., Triclistus matsiguenga, sp. n., Triclistus megantoniensis sp. n., Triclistus warmi sp. n. and Triclistus yungas sp. n. A key to Neotropical species is also presented, and four species group are suggested, based in the head and propodeum structure. PMID- 26146736 TI - Revision of the New World species of Erythrodolius (Hymenoptera: Ichneumonidae: Sisyrostolinae), with a key to the world species. AB - The genus Erythrodolius previously comprised ten species of ichneumonids: nine from Madagascar and one from Costa Rica. The current study revises the New World species of Erythrodolius including descriptions of three new species from Central America which brings the world total to 13 species: E. incompletus sp. n., E. luteus sp. n. and E. tenebrosus sp. n. A key to the world species is provided. Justification for the preference of the subfamily name Sisyrostolinae instead of Brachyscleromatinae is provided. PMID- 26146737 TI - Genus Cyptophania Banks (Psocodea: 'Psocoptera': Lepidopsocidae): unique features, augmented description of the generotype, and descriptions of three new species. AB - We define the genus Cyptophania with characters that clearly separate it from other genera of the Family Lepidopsocidae in which wing reduction has occurred. We redescribe the generotype, C. hirsuta Banks (Hawaii, presumably introduced), and describe three new species, C. australica n.sp. (Queensland, Australia), C. costalis n.sp. (Gulf of Mexico and Caribbean), and C. pakaratii n.sp. (Rapa Nui = Easter Island, probably endemic). The latter species is described from both sexes and presents the first males known for the genus. One female of this species presents a large spermatophore protruding from the genital chamber, thus indicating the mode of sperm transfer in sexual members of this genus. A key to the known species is included. All of the species of Cyptophania are highly neotenic, but differences in the level of neoteny are noted among the species studied. We question the synonymy of the genus Ptenocorium Enderlein with Cyptophania on the basis of several characters illustrated in the original description of Ptenocorium. We note similarities of Cyptophania to the entirely macropterous genus Lepidopsocus Enderlein and suggest a possible close relationship between the two genera. PMID- 26146738 TI - Notalina roraima Holzenthal 1986 (Trichoptera: Leptoceridae), male genitalia variability and larval description. AB - Notalina roraima Holzenthal 1986 was described on the basis of a single holotype specimen from the Pantepui Region. The species is a member of the endemic Neotropical long-horned caddisfly (Trichoptera: Leptoceridae) subgenus Notalina (Neonotalina) Holzenthal 1986. We present new records of this species and describe some morphological variation in the male genitalia. Moreover, we describe and illustrate the larva of this species and include information of its habitat. We also differentiate it from N. morsei, the only larva of the subgenus Neonotalina described until now. PMID- 26146739 TI - A new Crossodactylodes Cochran, 1938 (Anura: Leptodactylidae: Paratelmatobiinae) from the highlands of the Atlantic Forests of southern Bahia, Brazil. AB - A new Crossodactylodes is described from Serra das Lontras, in the highlands of the Atlantic Forests of southern Bahia. The new species can be distinguished from all other Crossodactylodes by having Finger I ending in an acute tip, a larger body size, by cranial features, and by molecular data. Like their congeners, the new species live in bromeliads but is widely geographically disjunct, being apparently restricted to the summit of a mountain range in Northeastern Brazil. PMID- 26146740 TI - Description of two new species of Walkerella (Pteromalidae, Otitesellinae) from China with a key to species of the genus. AB - Walkerella is an Old World genus of non-pollinating fig wasps in the subfamily Otitesellinae (Chalcidoidea, Pteromalidae). It is the most widely distributed genus of the subfamily, though there has been only six known world species. This paper describes two new species associated with the host Ficus subsection Conosycea of section Urostigma, subgenus Urostigma in Xishuangbanna, China. The two new species, Walkerella nigrabdomina Ma & Yang sp. nov. and W. curtipedis Ma & Yang sp. nov., are described from specimens reared from Ficus pisocarpa and Ficus curtipes, respectively. A key to all described species of Walkerella found is provided. PMID- 26146741 TI - First record of the genus Zaglyptus Forster (Hymenoptera: Ichneumonidae: Pimplinae) from Vietnam, with description of one new species. AB - The ichneumonid wasp genus Zaglyptus Forster, 1868 is reported for the first time from Vietnam, with three species found in the country. One new species, Zaglyptus guptai sp. nov., is described based on material collected in Chu Yang Sin NP, Dak Lak Province. Two other species, Z. glaber Gupta and Z. nigrolineatus, Gupta are recorded as new for the country. In addition, the subspecies Z glaber singaporensis Gupta is synonymised with the nominate subspecies. PMID- 26146742 TI - Chremistica ribhoi sp. n. (Hemiptera: Cicadidae) from North-East India and its mass emergence. AB - The genus Chremistica Stal, 1870 is reported from the northeastern region of India for the first time. A new species, Chremistica ribhoi, is described from this region and male genitalia illustrations and scanning electron microscope photographs of the pygofer for C. ribhoi are presented. Observations on mass emergence of C. ribhoi are described. PMID- 26146743 TI - A revision of the Australian species of Lynceus Muller, 1776 (Crustacea: Branchiopoda: Laevicaudata, Lynceidae). AB - Australia has had two species of Lynceus, L. macleayanus (King, 1855) and L. tatei (Brady, 1886) reported to date, both poorly described and without types, and supposedly both widely distributed. This study establishes neotypes and redescribes each according to modern standards. The present distribution of each is severely restricted by the destruction of temporary aquatic habitats, both in cities and in the country and also misunderstood by the lack of recent collecting in some outlying areas. Detailed study of male first thoracopods, together with an understanding of the form of the head and rostrum, antenna 2 spinal patterns, carapace shape, and the females' lamina abdominalis, most of which are discontinuously variable, has resulted in the delineation of four more species: L. baylyi sp. nov. in desert rockholes of Western Australia; L magdaleanae sp. nov. mainly in deep gnammas of the WA Wheatbelt and Goldfields but also extending into NT, Qld and SA; L. susanneae sp. nov. of rockholes on the Nullarbor Plain, WA; and L. argillaphilus sp. nov. of the coastal Pilbara, WA. Identification keys are provided for all six species, both males and females. PMID- 26146744 TI - Grassflies of the subfamily Chloropinae (Diptera: Chloropidae) from Vietnam and Thailand, with descriptions of two new species. AB - Seven genera of Chloropinae (Diptera: Chloropidae) from Vietnam and Thailand are discussed: Eurina Meigen (1 species), Chloromerus Becker (1 species), Siphlus Loew (1 species), Neoloxotaenia Sabrosky (3 species), Aragara Walker (1 species), Elachiptereicus Becker (1 species), Lagaroceras Becker (1 species). Some of them are new to the fauna of Vietnam and Thailand. Two new species are described: Chloromerus orientalis n. sp. from Thailand, and Lagaroceras tulense n. sp. from Vietnam and Thailand. The genus Chloromerus Becker, 1911 is recorded for the first time in the Oriental Region. The genus Semaranga Becker, 1911 is synonymised with Elachiptereicus Becker, 1909-syn. nov. A key to the Palaearctic and Oriental species of Lagaroceras Becker, 1903 is given. PMID- 26146745 TI - A new tree frog in the genus Polypedates (Anura: Rhacophoridae) from southern Thailand. AB - We describe a new species of Southeast Asian rhacophorid frog belonging to the Polypedates leucomystax species complex from Songkhla Province, southern Thailand. Polypedates discantus sp. nov. is distinguished from its congeners by the combination of having the skin of the head not co-ossified with the skull; absent or indistinct white dots on the back of the thigh; paired-vocal sac openings; and a round tubercle on the tibiotarsal articulation. The new species is also distinguished from P. leucomystax and P. megacephalus in univariate and multivariate analyses of quantitative morphometric characters, and has uncorrected pairwise distances of 6.61-7.16% from its closest relative, P. leucomystax, in the mitochondrial 16S rRNA gene. The new species has four distinct male advertisement call types, consisting of one-note, two-note, three note and staccato calls. The new species occurs syntopically with P leucomystax at the type locality. PMID- 26146746 TI - Three new species of Paraneseuthia Franz from Australia (Coleoptera, Staphylinidae, Scydmaeninae). AB - Three new species of the ant-like stone beetle genus Paraneseuthia (Eutheiini) are described from Australia: P bernierana sp. n. (Western Australia), P dilatifurculata sp. n. (Queensland) and P. angustifurculata sp. n. (Queensland). Key morphological characters of the new species are illustrated and discussed. Diagnoses of these and other species within the genus having similar body forms are based mainly on morphological differences in the male genitalia. New distributional data are given for Australian Paraneseuthia, based not only on named species but also on females recorded from coastal and sub-coastal eastern and northern regions that are not possible to identify in the absence of males. PMID- 26146747 TI - Elephantis, a new genus for Caridina natalensis Bouvier, 1925 from eastern rivers of Madagascar. AB - Elephantis, new genus, is established for Caridina natalensis Bouvier, 1925 hitherto known only from South Africa with one male specimen. Recently, three surveys by electric fishing (2004, 2008 and 2010) of some eastern rivers from Madagascar have permitted to discover numerous specimens of this species. Caridina natalensis is different from all other known species of Caridina by its remarkably broad endopod of the male first pleopod, a long clubbed appendix masculina on the male second pleopod reaching beyond distal end of endopod and strong third pereiopods. Therefore a new genus name is proposed for this species. In addition to detailed description of diagnostic morphological characters, molecular sequences obtained from mitochondrial 16S gene are provided for six specimens of this species. These DNA sequences are integrated to the 16S molecular phylogeny of atyid freshwater shrimps recently published by von Rintelen et al. (2012). Elephantis natalensis comb. nov. sequences formed a divergent group supported in maximum likelihood analysis. The availability of DNA samples could be used as reference and integrated in further phylogenetic studies on atyid freshwater shrimps. PMID- 26146748 TI - New species of Tetradiplosis (Diptera: Cecidomyiidae) inducing galls on Prosopis caldenia (Fabaceae) in Argentina. AB - Two new species of Tetradiplosis inducing galls on Prosopis caldenia are described from Argentina: Tetradiplosis panghitruz Martinez n. sp. and Tetradiplosis rayen Martinez n. sp. Tetradiplosispanghitruz induces multilocular galls on vegetative stems, whereas T. rayen induces unilocular galls containing multiple larvae on the rachis of the developing inflorescences. The adult male, female, pupa and larva are described and illustrated for both species. A key to the known species of the genus is provided. PMID- 26146749 TI - Redescription of the Oriental lace-bug Recaredus rex Distant, 1909 (Hemiptera: Tingidae: Tinginae), and its new tribal assignment, with a key to Ypsotingini. PMID- 26146750 TI - What Nurses and Patients Need to Know About Sipulecucel-T Immunotherapy for Prostate Cancer. PMID- 26146751 TI - HELLP Syndrome. How to recognize and treat this life-threatening complication of pregnancy. PMID- 26146752 TI - Howard Holtzer -- developmental and cell biologist 1922-2014. PMID- 26146753 TI - Seizure frequency reduction after posteromedial hypothalamus deep brain stimulation in drug-resistant epilepsy associated with intractable aggressive behavior. AB - OBJECTIVES: The aim of this study was to analyze the impact of deep brain stimulation (DBS) of the posteromedial hypothalamus (pHyp) on seizure frequency in patients with drug-resistant epilepsy (DRE) associated with intractable aggressive behavior (IAB). METHODS: Data were collected retrospectively from nine patients, who received bilateral stereotactic pHyp-DBS for the treatment of medically intractable aggressive behavior, focusing on five patients who also had DRE. All patients were treated at the Colombian Center and Foundation of Epilepsy and Neurological Diseases-FIRE (Chapter of the International Bureau for Epilepsy), in Cartagena de Indias, Colombia from 2010 to 2014. Each case was evaluated previously by the institutional ethical committee, assessing the impact of aggressive behavior on the patient's family and social life, the humanitarian aspects of preserving the safety and physical integrity of caregivers, and the need to prevent self-harm. Epilepsy improvement was measured by a monthly seizure reduction percentage, comparing preoperative state and outcome. Additional response to epilepsy was defined by reduction of the antiepileptic drugs (AEDs). Aggressive behavior response was measured using the Overt Aggression Scale (OAS). RESULTS: All the patients with DRE associated with IAB presented a significant decrease of the rate of epileptic seizures after up to 4 years follow-up, achieving a general 89.6% average seizure reduction from the state before the surgery. Aggressiveness was significantly controlled, with evident improvement in the OAS, enhancing the quality of life of patients and families. SIGNIFICANCE: In well-selected patients, DBS of the pHyp seems to be a safe and effective procedure for treatment of DRE associated with refractory aggressive behavior. Larger and prospective series are needed to define the pHyp as a target for DRE in different contexts. PMID- 26146754 TI - Surface Ligand Dynamics-Guided Preparation of Quantum Dots-Cellulose Composites for Light-Emitting Diodes. AB - Surface ligand dynamics of colloidal quantum dots (QDs) has been revealed as an important issue for determining QDs performance in their synthesis and postsynthesis treatment, such as ligand-related photoluminescence, colloidal stability, and so forth. However, this issue is less associated with the preparation of highly luminescent nanocomposites, which usually leads to poor performance and repeatability. In this work, on the basis of the studies about surface ligand dynamics of aqueous QDs, highly luminescent QDs-cellulose composites are prepared and employed to fabricate high color purity light emitting diodes (LEDs). Detailed investigations indicate that the species of QD capping ligands and in particular the temperature are the key for controlling the ligand dynamics. The preparation of nanocomposites using less dynamic ligand modified QDs at low temperature overcomes the conventional problems of QD aggregation, low QD content, luminescence quenching and shift, thus producing highly luminescent QDs-cellulose composites. This protocol is available for a variety of aqueous QDs, such as CdS, CdSe, CdTe, and CdSe(x)Te(1-x), which permits the design and fabrication of QD-based LEDs using the nanocomposites as color conversion layer on a blue emitting InGaN chip. PMID- 26146756 TI - Intensely Suicidal Behavior with a First Manic Episode. PMID- 26146757 TI - Improving Psychiatry Residents' Attitudes Toward Individuals Diagnosed with Substance Use Disorders. AB - Special attention needs to be paid to the attitudes of psychiatry residents toward individuals diagnosed with substance use disorders. The attitudes of trainees may be worse toward these individuals than toward individuals with other diagnoses, and these attitudes may worsen over time. While psychiatry residencies are increasingly teaching residents about how to diagnosis and treat individuals diagnosed with substance use disorders, more attention needs to be paid to educating residents about common attitudes toward these individuals. We recommend that psychiatry residency programs start with basic educational didactics and reflection exercises on attitudes toward individuals diagnosed with substance use disorders and that programs try to form a positive "hidden curriculum" in their institutions. PMID- 26146755 TI - Connectivity in Autism: A Review of MRI Connectivity Studies. AB - Autism spectrum disorder (ASD) affects 1 in 50 children between the ages of 6 and 17 years. The etiology of ASD is not precisely known. ASD is an umbrella term, which includes both low- (IQ < 70) and high-functioning (IQ > 70) individuals. A better understanding of the disorder and how it manifests in individual subjects can lead to more effective intervention plans to fulfill the individual's treatment needs.Magnetic resonance imaging (MRI) is a non-invasive investigational tool that can be used to study the ways in which the brain develops or deviates from the typical developmental trajectory. MRI offers insights into the structure, function, and metabolism of the brain. In this article, we review published studies on brain connectivity changes in ASD using either resting state functional MRI or diffusion tensor imaging.The general findings of decreases in white matter integrity and in long-range neural coherence are well known in the ASD literature. Nevertheless, the detailed localization of these findings remains uncertain, and few studies link these changes in connectivity with the behavioral phenotype of the disorder. With the help of data sharing and large-scale analytic efforts, however, the field is advancing toward several convergent themes, including the reduced functional coherence of long-range intra-hemispheric cortico-cortical default mode circuitry, impaired inter-hemispheric regulation, and an associated, perhaps compensatory, increase in local and short-range cortico-subcortical coherence. PMID- 26146758 TI - Ocular bartonellosis in transplant recipients: two case reports and review of the literature. AB - Cat scratch disease is caused by Bartonella henselae and usually manifests as localized lymphadenopathy and fever in immunocompetent patients. Immunocompromised patients are at risk for developing disseminated disease affecting the liver, spleen, eyes, central nervous system, and other organs. Bartonellosis is infrequently reported in solid organ transplant recipients, and published case reports usually discuss disseminated infection. Localized ocular disease with B. henselae, while well documented in immunocompetent hosts, is uncommon in immunocompromised patients. Herein, we present 2 cases of ocular bartonellosis in renal transplant patients, 1 with disseminated infection, and 1 without. PMID- 26146759 TI - Elucidation and Total Synthesis of the Correct Structures of Tridecapeptides Yaku'amides A and B. Synthesis-Driven Stereochemical Reassignment of Four Amino Acid Residues. AB - Yaku'amides A (1) and B (2) possess four alpha,beta-dehydroamino acid residues in their linear tridecapeptide sequence and differ in their residue-3 (Gly for 1 and Ala for 2). The highly unsaturated peptide structure, characteristic cytotoxicity profile, and extreme scarcity from natural sources motivated us to launch synthetic studies of 1 and 2. Here, we report the total synthesis of the originally proposed structure of yaku'amide B (2a) by applying the route to 1a, which was previously established in our group. However, this accomplishment only proved that 2a and natural 2 were structurally different and prompted investigations directed toward determining the true structure of 2. Extensive Marfey's analyses of minute amounts of natural 2 and its degradation products presented us the possible stereoisomers, all of which were synthetically prepared for chromatographic comparison with the authentic fragments of 2. Based on this detective work, we proposed a corrected structure for yaku'amide B (2c), in which the orders of residues-7 and -8 and residues-11 and -12 are reversed. Finally, the total synthesis of 2c led to confirmation of its structural identity. Moreover, the revised structure of yaku'amide A (1c) was constructed by switching Ala-3 to Gly-3 and was found to be chromatographically matched with the re isolated natural 1. The present work demonstrated the high reliability and sensitivity of the MS- and LC-based structural analyses and the indispensable role of chemical synthesis in structural elucidation of scarce natural products. PMID- 26146760 TI - MDM2 Amplification in Problematic Lipomatous Tumors: Analysis of FISH Testing Criteria. AB - To discriminate lipomas from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) we perform fluorescence in situ hybridization (FISH) for MDM2 amplification in several problematic situations: "lipomas" >10 cm, lesions with equivocal atypia, recurrent "lipomas," all retroperitoneal/pelvic/abdominal "lipomas", and in cases not fitting the above criteria but having worrisome clinical or radiologic features. To ascertain the validity of these criteria, we have reviewed our experience with 301 consecutive differentiated lipomatous tumors in which the diagnosis of ALT could not be established on the basis of histologic sections and in which FISH was performed on the basis of the above criteria. The final diagnosis was based on MDM2 amplification status. Given the nature of this study to evaluate difficult lesions, most cases included (74%) were received in consultation. This enhanced our study series for borderline cases, and the data presented may not be generalizable to adipocytic tumors seen outside a subspecialty setting. Of 301 cases, 108 proved to be ALT/WDL (36%). The most common test indication was size >10 cm (n=187), followed by equivocal atypia (n=145), retroperitoneal/pelvic/abdominal location (n=86), recurrence (n=33), and clinical concern (n=12). Of the tumors >10 cm, 68 (36%) proved to be ALT/WDL, whereas the remainder were interpreted as lipoma or its variants (eg, spindle cell or pleomorphic lipoma). The 2 groups did not differ statistically in size, although ALTs consistently occurred in patients above 50 years of age. Of the cases with equivocal atypia, 72 (50%) proved to be ALT/WDL. Those in the retroperitoneum/abdomen/pelvis were ALT/WDL in 30 cases (35%), and those that had recurred were ALT in 18 cases (55%). Recurrence, atypia, and having multiple indications for testing were more common in ALT than in benign lesions (P=0.02, 0.0001, 0.0012, respectively). No ALT/WDL occurred in the hands and feet, and only a single ALT/WDL was superficial (1 ALT/WDL vs. 60 lipoma/spindle cell or pleomorphic lipoma). Small (<10 cm) retroperitoneal tumors without additional features were always benign (n=9). On the basis of our results, FISH testing is recommended for: (1) recurrent lesions; (2) deep extremity lesions that are >10 cm in patients over 50 years of age; (3) in cases with equivocal atypia; (4) in lesions of the retroperitoneum/pelvis/abdomen, and in special clinical situations as directed by treating clinicians. Testing is low yield in superficial lesions, in small extremity lesions without additional indicators for testing, in large extremity lesions without additional features in patients under the age of 50, and in lesions arising in the hands/feet. More evidence is needed regarding testing in small retroperitoneal lesions without additional features. By adopting these criteria, we could have avoided testing 74 cases, missing a single superficial ALT/WDL. PMID- 26146761 TI - Upper body heavy strength training does not affect performance in junior female cross-country skiers. AB - We investigated the effects of adding heavy strength training to a high volume of endurance training on performance and related physiological determinants in junior female cross-country skiers. Sixteen well-trained athletes (17 +/- 1 years, 60 +/- 6 kg, 169 +/- 6 cm, VO2max running: 60 +/- 5 mL/kg/min) were assigned either to an intervention group (INT; n = 9) or a control group (CON; n = 7). INT completed two weekly sessions of upper body heavy strength training in a linear periodized fashion for 10 weeks. Both groups continued their normal aerobic endurance and muscular endurance training. One repetition maximum in seated pull-down increased significantly more in INT than in CON, with a group difference of 15 +/- 8% (P < 0.01). Performance, expressed as average power output on a double poling ergometer over 20 s and as 3 min with maximal effort in both rested (sprint-test) and fatigued states (finishing-test), showed similar changes in both groups. Submaximal O2 -cost and VO2peak in double poling showed similar changes or were unchanged in both groups. In conclusion, 10 weeks of heavy strength training increased upper body strength but had trivial effects on performance in a double poling ergometer in junior female cross-country skiers. PMID- 26146762 TI - The choice and measurement of fluence in photodynamic therapy for superficial basal cell carcinoma. PMID- 26146763 TI - Altered Distribution of Peripheral Blood Maturation-Associated B-Cell Subsets in Chronic Alcoholism. AB - BACKGROUND: Although decreased counts of peripheral blood (PB) B cells-associated with an apparently contradictory polyclonal hypergammaglobulinemia-have been reported in chronic alcoholism, no information exists about the specific subsets of circulating B cells altered and their relationship with antibody production. Here, we analyzed for the first time the distribution of multiple maturation associated subpopulations of PB B cells in alcoholism and its potential relationship with the onset of liver disease. METHODS: PB samples from 35 male patients-20 had alcoholic hepatitis (AH) and 15 chronic alcoholism without liver disease (AWLD)-were studied, in parallel to 19 male healthy donors (controls). The distribution of PB B-cell subsets (immature/regulatory, naive, CD27(-) and CD27(+) memory B lymphocytes, and circulating plasmablasts of distinct immunoglobulin-Ig-isotypes) was analyzed by flow cytometry. RESULTS: Patients with AH showed significantly decreased numbers of total PB B lymphocytes (vs. controls and AWLD), at the expense of immature, memory, and, to a lesser extent, also naive B cells. AWLD showed reduced numbers of immature and naive B cells (vs. controls), but higher PB counts of plasmablasts (vs. the other 2 groups). Although PB memory B cells were reduced among the patients, the percentage of surface (s)IgA(+) cells (particularly CD27(-) /sIgA(+) cells) was increased in AH, whereas both sIgG(+) and sIgA(+) memory B cells were significantly overrepresented in AWLD versus healthy donors. Regarding circulating plasmablasts, patients with AH only showed significantly reduced counts of sIgG(+) cells versus controls. In contrast, the proportion of both sIgA(+) and sIgG(+) plasmablasts-from all plasmablasts-was reduced in AH and increased in AWLD (vs. the other 2 groups). CONCLUSIONS: AH and AWLD patients display a significantly reduced PB B-cell count, at the expense of decreased numbers of recently produced immature/regulatory B cells and naive B cells, together with an increase in Ig-switched memory B lymphocytes and plasmablasts, particularly of IgA(+) cells. PMID- 26146764 TI - Serum HBsAg kinetics and usefulness of interferon-inducible protein 10 serum in HBeAg-negative chronic hepatitis B patients treated with tenofovir disoproxil fumarate. AB - The kinetics of serum HBsAg and interferon-inducible protein 10 (IP10) levels in patients with chronic hepatitis B infection treated with tenofovir are unclear. We evaluated the changes of HBsAg levels and the predictability of IP10 for HBsAg decline in 160 HBeAg-negative patients receiving tenofovir for >=12 months. Serum samples taken before and at 6, 12, 24, 36 and 48 months after tenofovir were tested for HBsAg levels. In 104 patients, serum samples before tenofovir were tested for IP10 levels. Compared to before tenofovir, HBsAg levels decreased by a median of 0.08, 0.11, 0.24, 0.33 and 0.38 log10 IU/mL at 6, 12, 24, 36 and 48 months, respectively (P < 0.001). HBsAg kinetics did not differ between nucleos(t)ide analogue(s) naive and experienced patients. The 12-, 24-, 36- and 48-month cumulative rates of >=0.5 log10 HBsAg decline were 8%, 16%, 24% and 41% and of HBsAg <=100 IU/mL were 9%, 12%, 14% and 18%, respectively. The only factor associated with HBsAg <=100 IU/mL was lower HBsAg levels before tenofovir (P < 0.001), while HBsAg decline >=0.5 log10 was associated with higher IP10 levels (P = 0.002) and particularly with IP10 > 350 pg/mL (P < 0.001). In conclusion, tenofovir decreases serum HBsAg levels in both nucleos(t)ide analogue(s) naive and experienced patients with HBeAg-negative chronic hepatitis B infection. After 4 years of therapy, HBsAg <=100 IU/mL can be achieved in approximately 20% of patients, particularly in those with low baseline HBsAg levels. HBsAg decline is slow (>=0.5 log10 in 40% of patients after 4 years) and is associated only with higher baseline serum IP10 levels. PMID- 26146765 TI - Conjunctival and intraocular swabs for the microbiological assessment of donor corneas. AB - PURPOSE: In this study, we investigated the associations between conjunctival (co) and intraocular (io) swabs and their implications for the contamination rates of organ-cultured corneas. METHODS: A total of 4177 swabs from 1054 corneas of 527 donors were acquired from the conjunctiva, after disinfection with 5% polyvinylpyrrolidone-iodine solution, and also from the anterior chamber after corneoscleral trepanation (io). Samples were incubated at 22.5 +/- 2.5 degrees C and 32.5 +/- 2.5 degrees C in thioglycollate broth for 14 days. Donor corneas were cultured in a closed system at 31 degrees C. Microbial differentiation was performed for positive cultures. RESULTS: A higher temperature (32.5 degrees C) and the intraocular swab retrieving localization led to significantly higher swab positive rates (32.5 degrees C versus 22.5 degrees C, odds 1.65, p < 0.0001; io versus co, odds 1,53, p < 0.0001). Death-to-collection time and laterality (left or right eye) had no significant influence on swab positivity. The cause of death significantly influenced the positive rates (p < 0.0001). Detection at 32.5 degrees C occurred significantly earlier than at 22.5 degrees C (p < 0.0001). The overall comparison of detected species showed no significant differences in the variety between intraocular and conjunctival swabs. During the study period, six contaminations of organ-cultured corneas occurred: four times Pseudomonas aeruginosa and once each Candida albicans and Staphylococcus hominis were found. Swap results and cornea contaminations were not significantly correlated. CONCLUSIONS: Co and io swabs show high microbial colonization rates, even after standard disinfection. Io swabs generally reproduce the co microbial range, most likely due to a mobilization and diversion of microorganisms during the trepanation procedure. Swab results do not yield a valuable tool to predict contaminations of organ-cultured corneas. PMID- 26146766 TI - The European Stroke Organisation Guidelines: a standard operating procedure. AB - In 2008, the recently founded European Stroke Organisation published its guidelines for the management of ischemic stroke and transient ischemic attack. This highly cited document was translated in several languages and was updated in 2009. Since then, the European Stroke Organisation has published guidelines for the management of intracranial aneurysms and subarachnoidal hemorrhage, for the establishment of stroke units and stroke centers, and recently for the management of intracerebral hemorrhage. In recent years, the methodology for the development of guidelines has evolved significantly. To keep pace with this progress and driven by the strong determination of the European Stroke Organisation to further promote stroke management, education, and research, the European Stroke Organisation decided to delineate a detailed standard operating procedure for its guidelines. There are two important cornerstones in this standard operating procedure: The first is the implementation of the Grading of Recommendations Assessment, Development, and Evaluation methodology for the development of its Guideline Documents. The second one is the decision of the European Stroke Organisation to move from the classical model of a single Guideline Document about a major topic (e.g. management of ischemic stroke) to focused modules (i.e. subdivisions of a major topic). This will enable the European Stroke Organisation to react faster when new developments in a specific stroke field occur and update its recommendations on the related module rather swiftly; with the previous approach of a single large Guideline Document, its entire revision had to be completed before an updated publication, delaying the production of up-to-date guidelines. After discussion within the European Stroke Organisation Guidelines Committee and significant input from European Stroke Organisation members as well as methodologists and analysts, this document presents the official standard operating procedure for the development of the Guideline Documents of the European Stroke Organisation. PMID- 26146767 TI - Holographic fluorescence microscopy with incoherent digital holographic adaptive optics. AB - Introduction of adaptive optics technology into astronomy and ophthalmology has made great contributions in these fields, allowing one to recover images blurred by atmospheric turbulence or aberrations of the eye. Similar adaptive optics improvement in microscopic imaging is also of interest to researchers using various techniques. Current technology of adaptive optics typically contains three key elements: a wavefront sensor, wavefront corrector, and controller. These hardware elements tend to be bulky, expensive, and limited in resolution, involving, for example, lenslet arrays for sensing or multiactuator deformable mirrors for correcting. We have previously introduced an alternate approach based on unique capabilities of digital holography, namely direct access to the phase profile of an optical field and the ability to numerically manipulate the phase profile. We have also demonstrated that direct access and compensation of the phase profile are possible not only with conventional coherent digital holography, but also with a new type of digital holography using incoherent light: selfinterference incoherent digital holography (SIDH). The SIDH generates a complex-i.e., amplitude plus phase-hologram from one or several interferograms acquired with incoherent light, such as LEDs, lamps, sunlight, or fluorescence. The complex point spread function can be measured using guide star illumination and it allows deterministic deconvolution of the full-field image. We present experimental demonstration of aberration compensation in holographic fluorescence microscopy using SIDH. Adaptive optics by SIDH provides new tools for improved cellular fluorescence microscopy through intact tissue layers or other types of aberrant media. PMID- 26146768 TI - Design and development of SMEDDS for colon-specific drug delivery. AB - CONTEXT: Lipoidal systems have particularly shown potential for specific accumulation in areas with inflamed tissue increasing the selectivity of local drug delivery. OBJECTIVE: Formulation and evaluation of self-microemulsifying drug delivery system (SMEDDS) for colon-specific drug delivery for effective treatment of colonic diseases. METHOD: Ternary phase diagram was used to optimize level of oil, surfactant and co-surfactant to optimize SMEDDS and were evaluated for percent transmittance, emulsification time, in vitro release, myeloperoxidase (MPO) activity and intestinal accumulation. The spray dried SMEDDS were filled in capsules which were enteric coated with Eudragit S-100 at 10% weight gain to ensure SMEDDS delivery at colon. The spray dried SMEDDS were also evaluated for IR, DSC, XRD, SEM and stability study. RESULT: In ternary phase diagram, Capmul MCM C8 and Capmul PG12 NF with surfactant (Tween 20) and co-surfactant (PG) in ratio 2:1 and 3:1, respectively, showed maximum emulsification area. These liquid SMEDDS show maximum transmittance, globule size of 90-30 nm. The spray-dried SMEDDS with diluents show good flow property. The units of MPO activity show lower level as compared to pure drug and control group, histopathology results supports better healing with SMEDDS. This was attributed to accumulation of SMEDDS in inflammatory area as compared to drug which was further proved by accumulation study. Enteric-coated capsule containing SMEDDS are able to deliver drug, specifically at the colonic region. CONCLUSION: Higher accumulation of lipoidal drug in inflammatory area and specific release of liposomes by enteric coated capsules provide better option for the treatment of colonic disease. PMID- 26146770 TI - Preparation and evaluation of floating tablets of pregabalin. AB - Floating tablets of pregabalin were prepared using different concentrations of the gums (xanthan gum and guar gum), Carbopol 974P NF and HPMC K100. Optimized formulations were studied for physical tests, floating time, swelling behavior, in vitro release studies and stability studies. In vitro drug release was higher for tablet batches containing guar and xanthan gum as compared to the batches containing Carbopol 974P NF. Tablet batches were subjected to stability studies and evaluated by different parameters (drug release, drug content, FTIR and DSC studies). The optimized tablet batch was selected for in vivo pharmacodynamic studies (PTZ induced seizures). The results obtained showed that the onset of jerks and clonus were delayed and extensor phase was abolished with time in treated groups. A significant difference (p > 0.05) was observed in control and treated group behavior indicating an excellent activity of the formulation for a longer period (>12 h). PMID- 26146769 TI - Evaluation of the tamper-resistant properties of biphasic immediate release/extended-release oxycodone/acetaminophen tablets. AB - CONTEXT: Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release. OBJECTIVE: To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets. MATERIALS AND METHODS: IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet. RESULTS: IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol. DISCUSSION: IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets. CONCLUSION: IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets. PMID- 26146771 TI - Mental disabilities in an Aboriginal context. AB - Aboriginal (meaning original peoples) North American mental health is acknowledged to be in a more precarious state than that of the dominant cultures. Disability arises from the conditions of poverty, homelessness, and lack of resources that are compounded for North American aboriginal people by the historical trauma of conquest, being placed on reservations, residential schools, and continued discrimination. We present culturally sensitive and syntonic intervention programs that can reduce the impact of Aboriginal mental disabilities and discuss the commonality among these programs of celebrating culture, language, and tradition. PMID- 26146776 TI - The "Heart"-Shaped Flap for Soft-Tissue Reconstruction in Complex Avulsion Injury of the Hand. PMID- 26146777 TI - Reply: Microsurgical Scalp Reconstruction in the Elderly: A Systematic Review and Pooled Analysis of the Current Data. PMID- 26146778 TI - Reply: The Search for the Ideal Thin Skin Flap: Superficial Circumflex Iliac Artery Perforator Flap. A Review of 210 Cases. PMID- 26146779 TI - Microsurgical Scalp Reconstruction in the Elderly: A Systematic Review and Pooled Analysis of the Current Data. PMID- 26146780 TI - Analysis of the Surgical Treatments of 63 Keloids on the Cartilaginous Part of the Auricle: Effectiveness of the Core Excision Method. PMID- 26146781 TI - A Decade of Conflict: Flap Coverage Options and Outcomes in Traumatic War-Related Extremity Reconstruction. PMID- 26146782 TI - Reply: A Decade of Conflict: Flap Coverage Options and Outcomes in Traumatic War Related Extremity Reconstruction. PMID- 26146783 TI - Analysis of the Surgical Treatments of 63 Keloids on the Cartilaginous Part of the Auricle: Effectiveness of the Core Excision Method. PMID- 26146784 TI - Chasing Michelangelo Buonarroti's Greatness. PMID- 26146785 TI - Reply: Analysis of the Surgical Treatments of 63 Keloids on the Cartilaginous Part of the Auricle: Effectiveness of the Core Excision Method. PMID- 26146786 TI - Rationale and design of MUSIC OS-EU: an international observational study of the treatment of postmenopausal women for osteoporosis in Europe and Canada. AB - OBJECTIVES: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS-EU) was designed to better understand the rate and burden of gastrointestinal (GI) events on clinical and health care outcomes among postmenopausal women with osteoporosis. METHODS: MUSIC OS-EU is a prospective, multinational, observational cohort study of postmenopausal women >=50 years of age diagnosed with osteoporosis and enrolled in physician clinics in six countries: France, Italy, the Netherlands, Sweden, the United Kingdom, and Canada. The MUSIC OS-EU study has three components: (i) a physician survey to describe their management of osteoporotic patients with GI events; (ii) a retrospective chart survey to describe the receipt and type of osteoporosis medication prescribed; and (iii) a prospective cohort study including untreated and treated patients diagnosed with osteoporosis to investigate the rate of GI events and association with osteoporosis medication use patterns, health-related quality of life, treatment satisfaction and resource utilisation among postmenopausal women with osteoporosis. RESULTS: Physicians at 97 sites completed the physician questionnaire and data for 716 patients were abstracted for the retrospective chart review. Enrolment and the baseline data collection for the prospective cohort study were conducted between March 2012 and June 2013 for 292 untreated and 2,959 treated patients, of whom 684 were new users and 2,275 were experienced users of oral osteoporosis medications. CONCLUSIONS: The results of MUSIC OS-EU will illuminate the association of GI events with the management of osteoporosis and with patient-reported outcomes among postmenopausal women with osteoporosis in Europe and Canada. PMID- 26146787 TI - Reducing Environmental Toxicity of Silver Nanoparticles through Shape Control. AB - The use of antibacterial silver nanomaterials in consumer products ranging from textiles to toys has given rise to concerns over their environmental toxicity. These materials, primarily nanoparticles, have been shown to be toxic to a wide range of organisms; thus methods and materials that reduce their environmental toxicity while retaining their useful antibacterial properties can potentially solve this problem. Here we demonstrate that silver nanocubes display a lower toxicity toward the model plant species Lolium multiflorum while showing similar toxicity toward other environmentally relevant and model organisms (Danio rerio and Caenorhabditis elegans) and bacterial species (Esherichia coli, Bacillus cereus, and Pseudomonas aeruginosa) compared to quasi-spherical silver nanoparticles and silver nanowires. More specifically, in the L. multiflorum experiments, the roots of silver nanocube treated plants were 5.3% shorter than the control, while silver nanoparticle treated plant roots were 39.6% shorter than the control. The findings here could assist in the future development of new antibacterial products that cause less environmental toxicity after their intended use. PMID- 26146788 TI - Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for the Diagnosis and Subtyping of Lymphoma. AB - BACKGROUND: Excisional biopsies are typically used to diagnose lymphoma, but data suggest that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is equally effective. In this study, we determined whether EBUS-TBNA could accurately diagnose and subtype lymphoma. METHODS: The cases of patients who had undergone EBUS-TBNA for suspected lymphoma were retrospectively reviewed. EBUS-TBNA results were categorized as lymphoma, specific nonlymphoma diagnosis, granulomatous inflammation, or adequate or inadequate lymphocytes with no specific diagnosis. To quantify the ability of EBUS-TBNA to diagnose lymphoma, we used likelihood ratios. To quantify the ability of EBUS-TBNA to diagnose and subtype lymphoma, we calculated sensitivity and specificity. For this analysis, lymphoma that could be subtyped on the basis of EBUS-TBNA was classified as a true positive; lymphoma that could not be subtyped was classified as a false negative. RESULTS: Of the 181 patients included, 75 (41.5%) were ultimately diagnosed with lymphoma. EBUS-TBNA was able to establish a diagnosis of lymphoma in 63 patients (84%). Granulomatous inflammation diagnosed on the basis of EBUS TBNA was associated with a low likelihood of lymphoma being present (likelihood ratio, 0.00; 95% confidence interval [CI], 0.00-0.276). Adequate lymphocytes were associated with a low likelihood of lymphoma (LR, 0.25; 95% CI, 0.14-0.49). EBUS TBNA was able to establish a diagnosis and subtype the lymphoma in 67% (95% CI, 0.45-0.88) of patients with de novo lymphoma and 81% (95% CI, 0.70-0.91) of patients with relapsed lymphoma. CONCLUSIONS: EBUS-TBNA is an effective, minimally invasive diagnostic test for patients with suspected lymphoma and can provide valuable clinical information, even with "negative" results. PMID- 26146789 TI - Counterintuitive Religious Ideas and Metaphoric Thinking: An Event-Related Brain Potential Study. AB - It has been shown that counterintuitive ideas from mythological and religious texts are more acceptable than other (non-religious) world knowledge violations. In the present experiment we explored whether this relates to the way they are interpreted (literal vs. metaphorical). Participants were presented with verification questions that referred to either the literal or a metaphorical meaning of the sentence previously read (counterintuitive religious, counterintuitive non-religious and intuitive), in a block-wise design. Both behavioral and electrophysiological results converged. At variance to the literal interpretation of the sentences, the induced metaphorical interpretation specifically facilitated the integration (N400 amplitude decrease) of religious counterintuitions, whereas the semantic processing of non-religious counterintuitions was not affected by the interpretation mode. We suggest that religious ideas tend to operate like other instances of figurative language, such as metaphors, facilitating their acceptability despite their counterintuitive nature. PMID- 26146791 TI - Evaluation of a Spiral Groove Geometry for Improvement of Hemolysis Level in a Hydrodynamically Levitated Centrifugal Blood Pump. AB - The purpose of this study is to evaluate a spiral groove geometry for a thrust bearing to improve the hemolysis level in a hydrodynamically levitated centrifugal blood pump. We compared three geometric models: (i) the groove width is the same as the ridge width at any given polar coordinate (conventional model); (ii) the groove width contracts inward from 9.7 to 0.5 mm (contraction model); and (iii) the groove width expands inward from 0.5 to 4.2 mm (expansion model). To evaluate the hemolysis level, an impeller levitation performance test and in vitro hemolysis test were conducted using a mock circulation loop. In these tests, the driving conditions were set at a pressure head of 200 mm Hg and a flow rate of 4.0 L/min. As a result of the impeller levitation performance test, the bottom bearing gaps of the contraction and conventional models were 88 and 25 MUm, respectively. The impeller of the expansion model touched the bottom housing. In the hemolysis test, the relative normalized index of hemolysis (NIH) ratios of the contraction model in comparison with BPX-80 and HPM-15 were 0.6 and 0.9, respectively. In contrast, the relative NIH ratios of the conventional model in comparison with BPX-80 and HPM-15 were 9.6 and 13.7, respectively. We confirmed that the contraction model achieved a large bearing gap and improved the hemolysis level in a hydrodynamically levitated centrifugal blood pump. PMID- 26146790 TI - Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression. AB - Hyperexcitability of the hippocampus is a commonly observed phenomenon in the years preceding a diagnosis of Alzheimer's disease (AD). Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(TauP301L)4510 mouse model of AD. To determine whether improving glutamate regulation would attenuate cognitive deficits and AD-related pathology, TauP301L mice were treated with riluzole (~ 12.5 mg/kg/day p.o.), an FDA-approved drug for amyotrophic lateral sclerosis that lowers extracellular glutamate levels. Riluzole-treated TauP301L mice exhibited improved performance in the water radial arm maze and the Morris water maze, associated with a decrease in glutamate release and an increase in glutamate uptake in the dentate gyrus, cornu ammonis 3 (CA3), and cornu ammonis 1 (CA1) regions of the hippocampus. Riluzole also attenuated the TauP301L-mediated increase in hippocampal vesicular glutamate transporter 1, which packages glutamate into vesicles and influences glutamate release; and the TauP301L-mediated decrease in hippocampal glutamate transporter 1, the major transporter responsible for removing glutamate from the extracellular space. The TauP301L-mediated reduction in PSD-95 expression, a marker of excitatory synapses in the hippocampus, was also rescued by riluzole. Riluzole treatment reduced total levels of tau, as well as the pathological phosphorylation and conformational changes in tau associated with the P301L mutation. These findings open new opportunities for the development of clinically applicable therapeutic approaches to regulate glutamate in vulnerable circuits for those at risk for the development of AD. PMID- 26146792 TI - Biochemistry in an undergraduate writing-intensive first-year program: Seminar courses in drugs and bioethics. AB - The College of the Holy Cross offers a universal first-year program called Montserrat, in which first-year students participate in a living-learning experience anchored by a yearlong seminar course. The seminar courses are part of a thematic cluster of four to eight courses; students in the cluster live together in a common dormitory and participate in shared co-curricular events designed to engage the entire cluster in intellectual discourse related to the theme. A two-semester seminar within the "Natural World" cluster was offered using biochemical principles as the underlying content. In the first semester, students were introduced to drug design, activity and abuse via student presentations and guided readings on ethnobotany, drug laws, drug use in religion, and prescription drug costs. In the second semester, students discussed primary readings in ethics followed by case study analyses of assisted reproduction technologies, informed consent, genetic privacy, performance enhancing drugs and genetically modified organisms. Student learning outcomes were evaluated via rubrics and a College-facilitated survey. PMID- 26146793 TI - Amitriptyline for neuropathic pain in adults. AB - BACKGROUND: This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of amitriptyline for fibromyalgia are now dealt with in a separate review.Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants. OBJECTIVES: To assess the analgesic efficacy of amitriptyline for relief of chronic neuropathic pain, and the adverse events associated with its use in clinical trials. SEARCH METHODS: We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with two clinical trial registries, and the reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own hand searched database for older studies. SELECTION CRITERIA: We included randomised, double-blind studies of at least four weeks' duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain conditions. DATA COLLECTION AND ANALYSIS: We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both. MAIN RESULTS: We included 15 studies from the earlier review and two new studies (17 studies, 1342 participants) in seven neuropathic pain conditions. Eight cross-over studies with 302 participants had a median of 36 participants, and nine parallel group studies with 1040 participants had a median of 84 participants. Study quality was modest, though most studies were at high risk of bias due to small size.There was no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition. Only third-tier evidence was available. For only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo (very low quality evidence).More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The risk ratio (RR) was 1.5 (95% confidence interval (CI) 1.3 to 1.8) and the number needed to treat for an additional harmful outcome was 5.2 (3.6 to 9.1) (low quality evidence). Serious adverse events were rare. Adverse event and all-cause withdrawals were not different, but were rarely reported (very low quality evidence). AUTHORS' CONCLUSIONS: Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many people with neuropathic pain. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain, but only a minority of people will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all. PMID- 26146794 TI - Basic versus applied research: Julius Sachs (1832-1897) and the experimental physiology of plants. AB - The German biologist Julius Sachs was the first to introduce controlled, accurate, quantitative experimentation into the botanical sciences, and is regarded as the founder of modern plant physiology. His seminal monograph Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) was published 150 y ago (1865), when Sachs was employed as a lecturer at the Agricultural Academy in Poppelsdorf/Bonn (now part of the University). This book marks the beginning of a new era of basic and applied plant science. In this contribution, I summarize the achievements of Sachs and outline his lasting legacy. In addition, I show that Sachs was one of the first biologists who integrated bacteria, which he considered to be descendants of fungi, into the botanical sciences and discussed their interaction with land plants (degradation of wood etc.). This "plant-microbe-view" of green organisms was extended and elaborated by the laboratory botanist Wilhelm Pfeffer (1845-1920), so that the term "Sachs-Pfeffer-Principle of Experimental Plant Research" appears to be appropriate to characterize this novel way of performing scientific studies on green, photoautotrophic organisms (embryophytes, algae, cyanobacteria). PMID- 26146795 TI - Influence of High Pressure on the Bending Rigidity of Model Membranes. AB - Curvature is a fundamental lipid membrane property that influences many membrane mediated biological processes and dynamic soft materials. One of the key parameters that determines the energetics of curvature change is the membrane bending rigidity. Understanding the intrinsic effect of pressure on membrane bending is critical to understanding the adaptation and structural behavior of biomembranes in deep-sea organisms as well as soft material processing. However, it has not previously been possible to measure the influence of high hydrostatic pressure on membrane bending energetics, and this bottleneck has primarily been due to a lack of technology platforms for performing such measurements. We have developed a new high-pressure microscopy cell which, combined with vesicle fluctuation analysis, has allowed us to make the first measurements of membrane bending rigidity as a function of pressure. Our results show a significant increase in bending rigidity at pressures up to 40 MPa. Above 40 MPa, the membrane mechanics become more complex. Corresponding small and wide-angle X-ray diffraction shows an increase in density and thickness of the bilayer with increasing pressure which correlates with the micromechanical measurements. These results are consistent with recent theoretical predictions of the bending rigidity as a function of hydrocarbon chain density. This technology has the potential to transform our quantitative understanding of the role of pressure in soft material processing, the structural behavior of biomembranes, and the adaptation mechanisms employed by deep-sea organisms. PMID- 26146796 TI - Feasibility and safety of a novel dedicated device for one-step EUS-guided biliary drainage: A randomized trial. AB - BACKGROUND AND AIMS: EUS-guided biliary drainage (EUS-BD) has been proposed as an alternative for patients after failed ERCP. To date, the evaluation of dedicated device for one-step EUS-BD has been limited. To determine feasibility and safety of a newly designed 7F stent introducer with tapered metal tip as a push-type dilator for one-step metal stent placement without additional fistula dilation in EUS-BD. METHODS: Thirty-two patients with malignant biliary obstruction and failed ERCP were randomly assigned to a dedicated stent introducer with a modified hybrid metal stent (DH group, n = 16) or a conventional 8.5F biliary metal stent introducer with a fully covered metal stent (FC group, n = 16). The technical success, procedural times, clinical success rate, and adverse event rates were evaluated. RESULTS: One-step technical success without additional fistula dilation in the DH was 88% (14/16). Multi-step process in a stent placement was performed in all patients of the FC group. The procedural time in the DH was significantly shorter than the FC (10 vs. 15 min, P = 0.007). No difference in overall technical or clinical success was seen between the groups. The rate of an early adverse event was common in the FC compared with the DH (31.3% [5/16] in the FC vs. 6.3% [1/16] in the DH, P = 0.172), although not statistically significant. CONCLUSIONS: A dedicated device for one-step EUS-BD may be technically feasible, safe, and shorten the procedural times with less chance of an additional fistula dilation process, resulting in a potential reduction of the early adverse events. PMID- 26146797 TI - Atmospheric and Aqueous Deposition of Polycrystalline Metal Oxides Using Mist-CVD for Highly Efficient Inverted Polymer Solar Cells. AB - Large scale, cost-effective processing of metal oxide thin films is critical for the fabrication of many novel thin film electronics. To date, however, most of the reported solution-based techniques require either extended thermal anneals or additional synthetic steps. Here we report mist chemical vapor deposition as a solution-based, readily scalable, and open-air method to produce high-quality polycrystalline metal oxide thin films. Continuous, smooth, and conformal deposition of metal oxide thin films is achieved by tuning the solvent chemistry of Leidenfrost droplets to promote finer control over the surface-local dissociation process of the atomized zinc-bearing precursors. We demonstrate the deposited ZnO as highly efficient electron transport layers for inverted polymer solar cells to show the power of the approach. A highest efficiency of 8.7% is achieved with a fill factor of 73%, comparable to that of conventional so-gel ZnO, which serves as an indication of the efficient vertical transport and electron collection achievable using this material. PMID- 26146798 TI - Can the Child Health Utility 9D measure be useful in oral health research? AB - BACKGROUND: Cost-utility analysis using the quality-adjusted life years (QALY) as an outcome measure to inform healthcare resource allocation is becoming more common. The Child Health Utility 9D (CHU9D) enables the calculation of utility values in children. Children were involved throughout its development to ensure it is child centred. AIM: To determine whether the CHU9D is responsive to the changing components of the dmfs+DMFS index score in children receiving dental care over a 1-year period. DESIGN: The study sample comprised children aged 6 to 9 years old who were enrolled in a split-mouth, placebo-controlled randomised controlled trial. All children had a comprehensive clinical examination including radiographs and health-related quality of life (HRQoL) was measured using the CHU9D at baseline and 1 year. Descriptive statistics was followed by bivariate analyses before effect sizes were calculated. A negative binomial model was fitted to assess whether the utility score predicted the components of decayed and filled teeth (combined primary and permanent teeth). RESULTS: Eighty (92%) children completed the CHU9D at baseline and follow-up. They presented with a mean baseline d3mfs+D3MFS of 6.7 (SD = 7.1), which rose to 7.3 (SD = 7.0) at follow-up. The mean CHU9D score improved from 0.88 to 0.90 from baseline to follow-up. No statistically significant relationships were found between caries status and the CHU9D score. CONCLUSION: The CHU9D was found to be unresponsive to the changing components of dental caries experience. PMID- 26146799 TI - Call for Papers on Adolescent and Young Adult Health. PMID- 26146800 TI - Standardless Quantification of Heavy Elements by Electron Probe Microanalysis. AB - Absolute Malpha and Mbeta X-ray intensities were measured for the elements Pt, Au, Pb, U, and Th by electron impact for energies ranging from 6 to 38 keV. Experimental data were obtained by measuring the X-ray intensity emitted from bulk samples with an electron microprobe using high-resolution wavelength dispersive spectrometers. Recorded X-ray intensities were converted into absolute X-ray yields by evaluation of the detector efficiency and then compared with X ray intensities calculated by means of Monte Carlo simulations. Simulated Malpha and Mbeta X-ray intensities were found to be in good agreement with the measurements, allowing their use in standardless quantification methods. A procedure and a software program were developed to accurately obtain virtual standard values. Standardless quantifications of Pb and U were tested on standards of PbS, PbTe, PbCl2, vanadinite, and UO2. PMID- 26146801 TI - Diagnostic Consistency and Relation Between Optical Coherence Tomography and Standard Automated Perimetry in Primary Open-Angle Glaucoma. AB - PURPOSE: To assess diagnostic consistency and relation between spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry (SAP) in patients with primary open-angle glaucoma (POAG). METHODS: This retrospective study comprised 51 eyes of 51 patients with a confirmed diagnosis of POAG. The qualitative and quantitative SD-OCT parameters (retinal nerve fiber layer thicknesses [RNFL; average, superior, inferior, nasal and temporal], RNFL symmetry, rim area, disc area, average and vertical cup/disc [C/D] ratio and cup volume) were compared with parameters of SAP (mean deviation, pattern standard deviation, visual field index, and glaucoma hemifield test reports). RESULTS: Fifty-one eyes of 51 patients with POAG were recruited. Twenty-nine eyes (56.9%) had consistent RNFL and visual field (VF) damage. However, nine patients (17.6%) showed isolated RNFL damage on SD-OCT and 13 patients (25.5%) had abnormal VF test with normal RNFL. In patients with VF defect, age, average C/D ratio, vertical C/D ratio, and cup volume were significantly higher and rim area was lower when compared to those of the patients with normal VF. In addition to these parameters, worsening in average, superior, inferior, and temporal RNFL thicknesses and RNFL symmetry was significantly associated with consistent SD-OCT and SAP outcomes. CONCLUSIONS: In routine practice, patients with POAG can be manifested with inconsistent reports between SD-OCT and SAP. An older age, higher C/D ratio, larger cup volume, and lower rim area on SD-OCT appears to be associated with detectable VF damage. Moreover, additional worsening in RNFL parameters might reinforce diagnostic consistency between SD-OCT and SAP. PMID- 26146802 TI - Non-myeloablative allogeneic hematopoietic stem cell transplantation for adults with relapsed and refractory mantle cell lymphoma: a single-center analysis in the rituximab era. AB - Relapsed and refractory (rel/ref) mantle cell lymphoma (MCL) portend a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potentially curative therapy in this setting. We analyzed the survival outcomes of 29 recipients of non-myeloablative allo-HSCT for rel/ref MCL, and studied possible prognostic factors in this setting. The cumulative incidences of disease progression and non-relapse mortality at 3 years were 28% (95% confidence interval (CI): 13-46%) and 29% (95% CI: 13-47%), respectively. The cumulative incidence of grade II-IV acute GvHD at days +100 and +180 was 34% (95% CI: 18-52%) and 45% (95% CI: 26-62%), respectively. With a median follow-up in survivors of 53 (range 24-83) months, the 3-year overall survival (OS) and PFS were 54% (95% CI: 38-76%) and 41% (95% CI: 26-64%), respectively. In vivo T-cell depletion with alemtuzumab (n=6) was associated with inferior 3-year PFS (0% vs 51%, P=0.007) and OS (17% vs 64%, P=0.014). Conversely, a second-line international prognostic index (sIPI) at transplantation equal to 0 (no risk factors) was associated with an improved 3-year PFS (52% vs 22%, P=0.020) and OS (71% vs 22%, P=0.006) compared with sIPI ?1. Performing an allo-HSCT before 2007 was associated with a decreased 3-year OS (25% vs 76%, P=0.015) but not with a significantly inferior PFS (17% vs 59%, P=0.058). In this single-center series, we report encouraging results with allo-HSCT for patients with rel/ref MCL. High alemtuzumab doses should probably be avoided in this context. PMID- 26146803 TI - Suggestive evidence of a role of HLA-DRB4 mismatches in the outcome of allogeneic hematopoietic stem cell transplantation with HLA-10/10-matched unrelated donors: a French-Swiss retrospective study. AB - We have conducted a retrospective study on 251 patients from three centers in France and Switzerland between 2004 and 2010 with the goal to evaluate the impact of HLA-DRB3/B4/B5 allele mismatching after HLA-10/10-matched unrelated allogeneic hematopoietic stem cell transplantation (HSCT). Fourteen (5.5%) patients receiving HSCT from an HLA-10/10-matched unrelated donor had a mismatched DRB4 donor, 23 (9.5%) patients had a mismatched DRB3 donor and 214 (85%) had a fully matched unrelated donor (HLA-10/10) without DRB3- or DRB4-mismatched donor. We compared the outcomes of 37 patients with a DRB3 or DRB4 mismatch with the rest of the population. The median survival for a patient without DRB3/4 mismatch was 18 months (95% confidence interval (CI), 13-29), for DRB3-mismatched patients 32 months (95% CI, 13-NR) and for DRB4-mismatched patients 7 months (95% CI, 3-NR). The multivariate analysis showed a significant impact of DRB4 mismatching on survival (Hazards ratio (HR)=2.1 (95% CI, 1.01-4.67), P=0.045), acute GvHD (HR=2.66 (95% CI, 0.99-7.09) P=0.05) and on transplant-related mortality (HR=2.8; (95% CI, 1.7-4.4) P=0.024). In the view of an impact of DRB4 locus mismatch on clinical outcome, it would be important to confirm this observation in a prospective study as it may be worth considering DRB4 in the unrelated donor selection. PMID- 26146804 TI - Rehabilitation referrals and outcomes in the early period after hematopoietic cell transplantation. AB - In a cohort of inpatient hematopoietic cell transplantation (HCT) recipients, we assessed patterns of referral to rehabilitation treatment, functional performance and short-term outcomes in patients who received post-transplant rehabilitation in comparison with those who did not. Among 201 first-time HCT recipients, 53 (26%) were referred to an inpatient rehabilitation provider, had an assessment of functional performance using the Functional Independence Measure scale and underwent rehabilitation treatments to address functional needs. Patients who received rehabilitation therapy were more likely to be females (P=0.02), older than 60 years of age (P=0.0146), employed (P=0.01), have hypertension (P=0.02), peripheral vascular disease (P=0.01) and pre-transplant Karnofsky Performance Score (KPS) <90 (P=0.02). Mean functional performance scores for transfers and ambulation increased significantly in the group with rehabilitation interventions (P=0.0022 and P<0.0001, respectively). There was no difference between the groups that did and did not receive rehabilitation treatments in 30-day re-admission rates. Patients who are 60 years of age or older, with pre-transplant KPS<90, and pre-transplant hypertension were more likely to be referred for rehabilitation treatments in the early period after HCT. Future studies should be designed to determine the optimal timing and cost effectiveness of functional assessment and rehabilitation treatments in this high-risk population. PMID- 26146805 TI - From initiation to eradication: the lifespan of an MLL-rearranged therapy-related paediatric AML. PMID- 26146806 TI - Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning. AB - We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years). PMID- 26146807 TI - Hematopoietic stem cell donation: psychological perspectives of pediatric sibling donors and their parents. AB - Allogeneic stem cell transplantation (SCT) is widely used for treatment of various life-threatening pediatric diseases. It is an intensive process that psychologically affects the whole family. Pediatric donors represent a very unique, underreported, group. The aim of this study is to investigate the sibling donors' and their parents' perspective on the donation process. The cohort included 36 sibling donors and 50 parents of pediatric patients who underwent allogeneic SCT between 1995 and 2010 and were alive at the time of the study. Mean age at donation was 14.78+/-8.350 years in donors' group and 8.22+/-4.639 years in parents' group. Data were collected by anonymous questionnaires. Three psychological dimensions were analyzed: donors' personal perspective; donor recipient interpersonal relationship and the influence of the donation on the family unit. Results showed that the donors experienced a wide range of complex emotional responses, positive and negative, whereas the parents' responses were mainly positive and less complex. This study presents both the sibling donor's and parents' perspective, giving a more complete picture of the donation process within the family. The effects of this intense experience of SCT has a long-term impact on the whole family, indicating the need for follow-up and psychosocial support. PMID- 26146808 TI - Human herpesvirus-6 acute limbic encephalitis after unrelated umbilical cord blood transplantation successfully treated with ganciclovir. PMID- 26146809 TI - The potential role of HLA-DRB1*11 in the development and outcome of haematopoietic stem cell transplantation-associated thrombotic microangiopathy. AB - Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT) with high mortality rate. We retrospectively studied the frequency, clinical and genetic associations and prognostic effect of TA-TMA, in a total of 425 consecutive adult patients, who underwent allo-HSCT for a malignant haematological condition between 2007 and 2013 at our single centre. TA-TMA developed in 19% of the patients. Unrelated donor type (P<0.001), acute GvHD grades II-IV (P<0.001), myeloablative conditioning regimens (P=0.003), tacrolimus based GvHD prophylaxis (P=0.003), CMV infection (P=0.003) and carriership for HLA DRB1*11 (P=0.034) were associated with the development of TA-TMA. Survival was adversely affected by the presence of TA-TMA (P<0.001). Among patients with TA TMA, the outcome of HLA-DRB1*11 carriers was significantly better compared with non-carriers (P=0.003). As a new finding, our observations suggest that the presence of HLA-DRB1*11 antigen contributes to the development of TA-TMA and affects the outcome. PMID- 26146811 TI - Gab1 amplifies signaling in response to low-intensity stimulation by HGF. AB - The receptor tyrosine kinases EGFR and Met induce phosphorylation of the docking protein Gab1, and there is evidence that Gab1 may have a role in the signaling from these receptors. Studying hepatocytes, we previously found that although Gab1 mechanistically interacted in different ways with EGFR and Met, it was involved in mitogenic signaling induced by both EGF and HGF. It has been reported that in EGFR, Gab1 is required particularly at a low dose of EGF. Whether this also applies to HGF/Met signaling has not been investigated. We have studied the role of Gab1 in activation of the Akt and ERK pathways at low- and high-intensity stimulation with EGF and HGF in cultured hepatocytes. In cells where Gab1 was depleted by a specific Gab1-directed siRNA, the EGF-induced phosphorylation of ERK was lowered and HGF-induced phosphorylation of both ERK and Akt was substantially reduced. These effects were more marked at low-dose HGF stimulation. The inhibitory consequence of Gab1 depletion was particularly pronounced for HGF-induced Akt phosphorylation. The results suggest that Gab1 is an important signal amplifier for low-intensity stimulation by HGF. PMID- 26146810 TI - Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse. AB - To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients. PMID- 26146812 TI - Dexamethasone-loaded biopolymeric nanoparticles promote gingival fibroblasts differentiation. AB - Polymer-based nanoparticles (NPs) can be efficiently used for the delivery of bioactive molecules for both in vitro and in vivo applications affording high drug loading and controlled release profiles. Within this framework polylactic-co glycolic acid (PLGA) NPs with a diameter of 290 +/- 41 nm have been fabricated and loaded with dexamethasone (DXM) using a patented procedure. The aim of the project was to setup a controlled delivery system to promote the in vitro differentiation of Human Gingival Fibroblasts (HGFs). First the uptake of fluorescent PLGA NPs by HGFs cells was investigated; then experiments were also addressed to analyze the specific cell response to DXM, in order to evaluate its functional efficiency in comparison with its conventional addition to the culture medium. The results showed that cells treated with DXM-loaded NPs acquired the osteoblast phenotype faster in comparison to those treated with the free drug. The slow and sustained release of DXM from PLGA NPs produced a constant and uniform concentration of drug inside cells with long-term and enhanced biochemical effects. PMID- 26146813 TI - Sun-induced fluorescence - a new probe of photosynthesis: First maps from the imaging spectrometer HyPlant. AB - Variations in photosynthesis still cause substantial uncertainties in predicting photosynthetic CO2 uptake rates and monitoring plant stress. Changes in actual photosynthesis that are not related to greenness of vegetation are difficult to measure by reflectance based optical remote sensing techniques. Several activities are underway to evaluate the sun-induced fluorescence signal on the ground and on a coarse spatial scale using space-borne imaging spectrometers. Intermediate-scale observations using airborne-based imaging spectroscopy, which are critical to bridge the existing gap between small-scale field studies and global observations, are still insufficient. Here we present the first validated maps of sun-induced fluorescence in that critical, intermediate spatial resolution, employing the novel airborne imaging spectrometer HyPlant. HyPlant has an unprecedented spectral resolution, which allows for the first time quantifying sun-induced fluorescence fluxes in physical units according to the Fraunhofer Line Depth Principle that exploits solar and atmospheric absorption bands. Maps of sun-induced fluorescence show a large spatial variability between different vegetation types, which complement classical remote sensing approaches. Different crop types largely differ in emitting fluorescence that additionally changes within the seasonal cycle and thus may be related to the seasonal activation and deactivation of the photosynthetic machinery. We argue that sun induced fluorescence emission is related to two processes: (i) the total absorbed radiation by photosynthetically active chlorophyll; and (ii) the functional status of actual photosynthesis and vegetation stress. PMID- 26146814 TI - Halo nevus: review of the literature and clinicopathologic findings. PMID- 26146815 TI - World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma. AB - Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of hepatocellular carcinoma (HCC). In order to assess the relative contribution of HBV and HCV to HCC worldwide, and identify changes over time, we conducted a systematic review of case series published up to the year 2014. Eligible studies had to report seroprevalence of both hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV), alone and in combination, for at least 20 adult HCC cases. Studies using a first-generation enzyme-linked immunosorbent assay test for HCV were excluded. A total of 119,000 HCC cases in 260 studies were included from 50 countries. Most European and American countries show a preponderance of HCV over HBV and a substantial fraction of viral marker-negative cases. Asian and African countries generally show a predominance of HBV. The fraction of HCV positive HCC cases is substantial in Taiwan, Mongolia, Japan, and Pakistan as well as in Western-Central Asia and Northern Africa. No eligible studies were available in Oceania, large parts of Africa, Eastern Europe, and Central Asia. The United States, Brazil, and Germany show evidence of higher prevalence of HCV in HCC since the year 2000. Conversely, Japan and Italy show a decline in the proportion of HCV-positive HCC. CONCLUSION: HBV and HCV are predominant causes of HCC in virtually all world areas, with a growing fraction of HCC cases in several countries attributable to HCV. PMID- 26146816 TI - Possibility of death sentence has divergent effect on verdicts for Black and White defendants. AB - When anticipating the imposition of the death penalty, jurors may be less inclined to convict defendants. On the other hand, minority defendants have been shown to be treated more punitively, particularly in capital cases. Given that the influence of anticipated sentence severity on verdicts may vary as a function of defendant race, the goal of this study was to test the independent and interactive effects of these factors. We conducted a survey-embedded experiment with a nationally representative sample to examine the effect on verdicts of sentence severity as a function of defendant race, presenting respondents with a triple murder trial summary that manipulated the maximum penalty (death vs. life without parole) and the race of the defendant. Respondents who were told life without-parole was the maximum sentence were not significantly more likely to convict Black (67.7%) than White (66.7%) defendants. However, when death was the maximum sentence, respondents presented with Black defendants were significantly more likely to convict (80.0%) than were those with White defendants (55.1%). The results indicate that the death penalty may be a cause of racial disparities in criminal justice, and implicate threats to civil rights and to effective criminal justice. PMID- 26146817 TI - Predicting reoffense in pedophilic child molesters by clinical diagnoses and risk assessment. AB - A Diagnostic and Statistical Manual of Mental Disorders (DSM)-based diagnosis of pedophilia has so far failed to predict sexual reoffense in convicted child molesters, probably because of its broad and unspecific conceptualization. In this study, therefore, we investigated the prognostic value of the subtype exclusive pedophilia and a series of customary risk assessment instruments (SSPI, Static-99, Stable-2007, VRS:SO) and the PCL-R in a sample of prison released pedophilic sexual offenders. First, we examined the convergent validity of risk assessment instruments (N = 261). Then, we calculated the predictive accuracy of the measures and diagnosis for sexual recidivism by ROC analyses and subsequent Cox regression (N = 189). Also, predictive values with more clinical immediacy were calculated (sensitivity, specificity, PPV and NPV). The VRS:SO, the SSPI, and the Static-99 significantly predicted sexual recidivism, as did a diagnosis of exclusive pedophilia. Also, the VRS:SO predicted sexual reoffense significantly better than the Stable-2007, the Static-99/Stable-2007 combined score, and the PCL-R. When used combined, only the VRS:SO and a diagnosis of exclusive pedophilia added incremental validity to each other. Our findings support that the clinical diagnosis of an exclusive pedophilia based on DSM criteria and VRS:SO defined risk factors can reliably discriminate higher from lower risk offenders, even within the select subgroup of pedophilic child molesters. PMID- 26146818 TI - Imminent Departures: Rapid Vaccination Strategies Designed to Induce Short-Term Immunogenicity for the Trip at Hand. PMID- 26146819 TI - What's New in Travel-Associated Dermatology? PMID- 26146820 TI - Severe Toxic Skin Reaction Caused by a Common Anemone and Identification of the Culprit Organism. AB - In a marine envenomation, identification of the culprit organism can be difficult. In this case report, we present our method to identify snakelocks anemone (Anemonia viridis or formerly Anemonia sulcata) as the culprit of a severe toxic skin reaction. A. viridis is one of the most common anemones of the Mediterranean Sea and the North Atlantic Ocean. It lives at a depth of up to 10 m. It is a member of the phylum Cnidaria, which includes jellyfish, anemones, hydroids, and corals. They have toxic organelles called cnidocysts that have the capacity to inject venom with microscopic harpoon-like structures. The cnidocysts of A. viridis may cause toxic and allergic reactions, and although its venom is one of the most studied cnidarian venoms, detailed case reports are rare. PMID- 26146821 TI - A Bubble Turtle: Bullous Contact Dermatitis After a Black Henna Tattoo in a Backpacker in Thailand. PMID- 26146822 TI - C-peptide modifies leptin and visfatin secretion in human adipose tissue. AB - OBJECTIVE: The effects of C-peptide on adipose tissue, an organ involved in the development of obesity and insulin resistance, are not yet well known. The aim of this study was to determine whether C-peptide could be involved in the regulation of the adipocytokine synthesis in human visceral adipose tissue. METHODS: The association between C-peptide and different serum adipocytokines, with an intravenous glucose tolerance test (IVGTT), and in an in vitro study in subjects without obesity and in subjects with morbid obesity were analyzed. RESULTS: In different multiple regression analysis models, C-peptide and C-peptide increase above basal levels during total IVGTT and between 0 and 10 min were associated positively with leptin and negatively with visfatin. Rhodamine-labeled C-peptide binds to human adipocytes, and this binding was blocked with excess of unlabeled C-peptide. Exposure of human visceral explants and adipocytes from subjects with morbid obesity to C-peptide at 1 and 10 nM induced a significant increase in leptin and a decrease in visfatin secretion. In subjects without obesity, these C peptide effects were found mainly at 10 nM. These effects can be inhibited by phosphatidylinositol 3-kinase (PI3K) or protein kinase B (PKB) inhibitors. CONCLUSIONS: C-peptide may be involved in the regulation of leptin and visfatin secretion, molecules intimately involved in energy homeostasis processes, through PI3K or PKB pathways. PMID- 26146823 TI - Immunologic and Virologic Progression in HIV Controllers: The Role of Viral "Blips" and Immune Activation in the ANRS CO21 CODEX Study. AB - Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm(3) or more than 200/mm(3) with a baseline count below 600/mm(3). Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations. Clinical characteristics, immune activation, ultrasensitive HIV VL and total HIV DNA were analyzed. Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5). Progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e. 1-2 years before progression) than non-progressors. ImmP had also lower CD4+T cell nadir and CD4+T cell count at inclusion, and VirP had higher HIV DNA levels in blood. T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors. In summary, the lasting loss of CD4+T cells, residual HIV replication and basal levels of immune activation appear to be major determinants of progression in HICs. These factors should be considered for adjusting their follow-up. PMID- 26146824 TI - Knowledge, Beliefs and Practices Regarding Antiretroviral Medications for HIV Prevention: Results from a Survey of Healthcare Providers in New England. AB - BACKGROUND: Antiretroviral treatment for HIV-infection before immunologic decline (early ART) and pre-exposure chemoprophylaxis (PrEP) can prevent HIV transmission, but routine adoption of these practices by clinicians has been limited. METHODS: Between September and December 2013, healthcare practitioners affiliated with a regional AIDS Education and Training Center in New England were invited to complete online surveys assessing knowledge, beliefs and practices regarding early ART and PrEP. Multivariable models were utilized to determine characteristics associated with prescribing intentions and practices. RESULTS: Surveys were completed by 184 practitioners. Respondent median age was 44 years, 58% were female, and 82% were white. Among ART-prescribing clinicians (61% of the entire sample), 64% were aware that HIV treatment guidelines from the Department of Health and Human Services recommended early ART, and 69% indicated they would prescribe ART to all HIV-infected patients irrespective of immunologic status. However, 77% of ART-prescribing clinicians would defer ART for patients not ready to initiate treatment. Three-fourths of all respondents were aware of guidance from the U.S. Centers for Disease Control and Prevention recommending PrEP provision, 19% had prescribed PrEP, and 58% of clinicians who had not prescribed PrEP anticipated future prescribing. Practitioners expressed theoretical concerns and perceived practical barriers to prescribing early ART and PrEP. Clinicians with higher percentages of HIV-infected patients (aOR 1.16 per 10% increase in proportion of patients with HIV-infection, 95% CI 1.01-1.34) and infectious diseases specialists (versus primary care physicians; aOR 3.32, 95% CI 0.98-11.2) were more likely to report intentions to prescribe early ART. Higher percentage of HIV-infected patients was also associated with having prescribed PrEP (aOR 1.19, 95% CI 1.06-1.34), whereas female gender (aOR 0.26, 95% CI 0.10-0.71) was associated with having not prescribed PrEP. CONCLUSIONS: These findings suggest many clinicians have shifted towards routinely recommending early ART, but not PrEP, so interventions to facilitate PrEP provision are needed. PMID- 26146825 TI - The Status of STAT3 and STAT5 in Human Breast Atypical Ductal Hyperplasia. AB - Signal Transducer and Activation of Transcription factors (STAT3 and STAT5) play important roles in breast epithelial cell differentiation, proliferation, and apoptosis. They have been investigated extensively in established breast cancer, but their activation status in precancerous lesions has not been reported. Formalin-fixed, paraffin-embedded archival tissues from 59 cases of atypical ductal hyperplasia (ADH) and 31 cases of normal human breast tissue as well as 21 cases of usual ductal hyperplasias (UDH) were obtained from the First Hospital of Jilin University, China, and stained for pSTAT3 and pSTAT5 by immunohistochemistry. The median percentage of pSTAT5+ cells in ADH was 12%, not significantly deviant from that in normal breast. The median percentage of pSTAT3+ cells in ADH was 30%, significantly higher than that of normal breast. pSTAT3 and pSTAT5 were exclusive of each other--they were detected in different ADHs or in different cells within the same ADHs. In addition, both pSTAT3 and pSTAT5 were produced in similar percentages of cells in ADHs from cancer-free patients vs. ADHs that were adjacent to an invasive cancer. Our finding of a complementary expression pattern of pSTAT3 and pSTAT5 in ADH suggests that these two transcription factors may have feedback inhibitory effects on each other during early stages of breast cancer evolution, and that disruption of this inverse relationship may be important in the progression from early lesions to cancer, which exhibits positive association between pSTAT3 and pSTAT5. PMID- 26146826 TI - The Phenotype of the C9ORF72 Expansion Carriers According to Revised Criteria for bvFTD. AB - BACKGROUND: The C9ORF72 expansion is one of the most common genetic etiologies observed with behavioural variant frontotemporal dementia (bvFTD). Revised diagnostic criteria for bvFTD (FTDC) were recently introduced but only a few studies have evaluated the accuracy of these criteria. OBJECTIVE: The objective of the study was to evaluate the applicability of the FTDC criteria and assess the psychiatric history of these patients. METHODS: The study examined 36 patients carrying the C9ORF72 expansion and suffering from bvFTD (N = 32) or from bvFTD with motor neuron disease (bvFTD-MND, N = 4). Neuropsychological, neuropsychiatric, structural brain imaging and PET/SPECT data were evaluated. RESULTS: We found 0.75 sensitivity (SD 0.44, 95%CI 0.57-0.87) for possible bvFTD and 0.64 (SD 0.44, 95%CI 0.57-0.87) for probable bvFTD. The sensitivity was even higher in bvFTD patients without MND, i.e., 0.81 for possible bvFTD and 0.69 for probable bvFTD. PET/SPECT was normal in 17.6% of scanned patients with bvFTD. A history of psychiatric symptoms (psychotic and/or mood symptoms) was detected in 61% of cases. CONCLUSIONS: The FTDC possible and probable bvFTD criteria seem to identify the majority of the C9ORF72 expansion carriers with bvFTD, even though they exhibit only a limited number of behavioral criteria but a significant amount of psychiatric symptoms. The presence of a normal PET/SPECT does not exclude the possibility the C9ORF72 associated bvFTD. PMID- 26146827 TI - Video-Assisted versus Open Lobectomy in Patients with Compromised Lung Function: A Literature Review and Meta-Analysis. AB - BACKGROUND: It has been suggested that video-assisted (VATS) lobectomy is safer than open lobectomy in patients with compromised lung function, but data regarding this are limited. We assessed acute outcomes of VATS compared to open lobectomy in these high-risk patients using a systematic literature review and meta-analysis of data. METHODS: The databases PubMed and Scopus were searched for studies published between 2000 and 2013 that reported mortality and morbidity of VATS in high-risk lung cancer patients defined as having compromised pulmonary or cardiopulmonary function. Study selection, data collection and critical assessment of the included studies were performed according to the recommendations of the Cochrane Collaboration. RESULTS: Three case-control studies and three case series that included 330 VATS and 257 open patients were identified for inclusion. Operative mortality, overall morbidity and pulmonary morbidity were 2.5%, 39.3%, 26.2% in VATS patients and 7.8%, 57.5%, 45.5% in open lobectomy group, respectively. VATS lobectomy patients experienced significantly lower pulmonary morbidity (RR = 0.45; 95% CI, 0.30 to 0.67; p = 0.0001), somewhat reduced operative mortality (RR = 0.51; 95% CI, 0.24 to 1.06; p = 0.07), but no significant difference in overall morbidity (RR = 0.68; 95% CI, 0.41 to 1.14; p = 0.14). CONCLUSION: The existing data suggest that VATS lobectomy is associated with lower risk for pulmonary morbidity compared with open lobectomy in lung cancer patients with compromised lung function. PMID- 26146828 TI - Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities. AB - BACKGROUND: To investigate the clinical efficacy and treatment toxicity of volume modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS: 205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria. RESULTS: The median follow-up period was 37.3 months (range, 6.3-45.1 months). The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2-3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively. CONCLUSIONS: VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy. PMID- 26146829 TI - The Screening Performance of Serum 1,3-Beta-D-Glucan in Patients with Invasive Fungal Diseases: A Meta-Analysis of Prospective Cohort Studies. AB - The serum 1,3-beta-D-glucan (BG) assay aids in the early diagnosis of invasive fungal diseases (IFDs) and has been approved for their diagnosis. However, reports on the screening performance of BG are scarce. We performed a meta analysis of data extracted from only prospective cohort studies to evaluate the screening performance of the BG assay in the diagnosis of IFDs. We specifically searched 4 databases (the PubMed, Web of Science, Elsevier, and Cochrane Collaboration databases) according to EORTC-MSG criteria. A total of 1068 patients in 11 studies were analyzed. Deeks' funnel plot asymmetry test suggested a low likelihood of publication bias for the included studies (p = 0.055). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve, with 95% confidence intervals, were 0.75(0.63,0.84), 0.87(0.81,0.92), 5.85(3.96,8.63), 0.30(0.20,0.45), 19.53(11.16,34.18), and 0.89(0.86,0.91), respectively. The findings of this meta-analysis suggest that the BG assay is a useful screening tool with high sensitivity and specificity for discriminating between patients with and without IFDs. In clinical practice, BG assay results should be evaluated together with clinical and microbiological findings. PMID- 26146830 TI - Indwelling versus Intermittent Urinary Catheterization following Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The purpose of this study is to compare the rates of urinary tract infection (UTI) and postoperative urinary retention (POUR) in patients undergoing lower limb arthroplasty after either indwelling urinary catheterization or intermittent urinary catheterization. METHODS: We conducted a meta-analysis of relevant randomized controlled trials (RCT) to compare the rates of UTI and POUR in patients undergoing total joint arthroplasty after either indwelling urinary catheterization or intermittent urinary catheterization. A comprehensive search was carried out to identify RCTs. Study-specific risk ratios (RR) with 95% confidence intervals (CI) were pooled. Additionally, a meta-regression analysis, as well as a sensitivity analysis, was performed to evaluate the heterogeneity. RESULTS: Nine RCTs with 1771 patients were included in this meta-analysis. The results showed that there was no significant difference in the rate of UTIs between indwelling catheterization and intermittent catheterization groups (P>0.05). Moreover, indwelling catheterization reduced the risk of POUR, versus intermittent catheterization, in total joint surgery (P<0.01). CONCLUSIONS: Based on the results of the meta-analysis, indwelling urinary catheterization, removed 24-48 h postoperatively, was superior to intermittent catheterization in preventing POUR. Furthermore, indwelling urinary catheterization with removal 24 to 48 hours postoperatively did not increase the risk of UTI. In patients with multiple risk factors for POUR undergoing total joint arthroplasty of lower limb, the preferred option should be indwelling urinary catheterization removed 24-48 h postoperatively. LEVEL OF EVIDENCE: Level I. PMID- 26146831 TI - Value of Information Analysis Applied to the Economic Evaluation of Interventions Aimed at Reducing Juvenile Delinquency: An Illustration. AB - OBJECTIVES: To investigate whether a value of information analysis, commonly applied in health care evaluations, is feasible and meaningful in the field of crime prevention. METHODS: Interventions aimed at reducing juvenile delinquency are increasingly being evaluated according to their cost-effectiveness. Results of cost-effectiveness models are subject to uncertainty in their cost and effect estimates. Further research can reduce that parameter uncertainty. The value of such further research can be estimated using a value of information analysis, as illustrated in the current study. We built upon an earlier published cost effectiveness model that demonstrated the comparison of two interventions aimed at reducing juvenile delinquency. Outcomes were presented as costs per criminal activity free year. RESULTS: At a societal willingness-to-pay of ?71,700 per criminal activity free year, further research to eliminate parameter uncertainty was valued at ?176 million. Therefore, in this illustrative analysis, the value of information analysis determined that society should be willing to spend a maximum of ?176 million in reducing decision uncertainty in the cost effectiveness of the two interventions. Moreover, the results suggest that reducing uncertainty in some specific model parameters might be more valuable than in others. CONCLUSIONS: Using a value of information framework to assess the value of conducting further research in the field of crime prevention proved to be feasible. The results were meaningful and can be interpreted according to health care evaluation studies. This analysis can be helpful in justifying additional research funds to further inform the reimbursement decision in regard to interventions for juvenile delinquents. PMID- 26146832 TI - Competitive Interactions between C. albicans, C. glabrata and C. krusei during Biofilm Formation and Development of Experimental Candidiasis. AB - In this study, we evaluated the interactions between Candida albicans, Candida krusei and Candida glabrata in mixed infections. Initially, these interactions were studied in biofilms formed in vitro. CFU/mL values of C. albicans were lower in mixed biofilms when compared to the single biofilms, verifying 77% and 89% of C. albicans reduction when this species was associated with C. glabrata and C. krusei, respectively. After that, we expanded this study for in vivo host models of experimental candidiasis. G. mellonella larvae were inoculated with monotypic and heterotypic Candida suspensions for analysis of survival rate and quantification of fungal cells in the haemolymph. In the groups with single infections, 100% of the larvae died within 18 h after infection with C. albicans. However, interaction groups achieved 100% mortality after 72 h of infection by C. albicans-C. glabrata and 96 h of infection by C. albicans-C. krusei. C. albicans CFU/mL values from larvae hemolymph were lower in the interacting groups compared with the monoespecies group after 12 h of infection. In addition, immunosuppressed mice were also inoculated with monotypic and heterotypic microbial suspensions to induce oral candidiasis. C. albicans CFU/mL values recovered from oral cavity of mice were higher in the group with single infection by C. albicans than the groups with mixed infections by C. albicans-C. glabrata and C. albicans-C. krusei. Moreover, the group with single infection by C. albicans had a higher degree of hyphae and epithelial changes in the tongue dorsum than the groups with mixed infections. We concluded that single infections by C. albicans were more harmful for animal models than mixed infections with non albicans species, suggesting that C. albicans establish competitive interactions with C. krusei and C. glabrata during biofilm formation and development of experimental candidiasis. PMID- 26146834 TI - Correction: The Challenging Road towards a Unified Animal Research Network in Europe. PMID- 26146833 TI - The Seropositivity of Toxocara spp. Antibodies in Pregnant Women Attented at the University Hospital in Southern Brazil and the Factors Associated with Infection. AB - BACKGROUND: Human toxocariasis is a parasitic zoonosis with a worldwide distribution but is underdiagnosed with an underestimated impact on human health. The ingestion of embryonated eggs of Toxocara spp. present on the hands or in contaminated food or water is the main mode of infection. The only record of Toxocara congenital infection in humans occurred in a premature infant. Helminth infections during pregnancy may be associated with reproductive disorders. Studies investigating the occurrence of toxocariasis in pregnancy are scarce, as is research on the possible implications of these parasites in reproductive health. The aim of this study was to determine the seroprevalence of antibodies to Toxocara spp. in pregnant women and to identify risk factors associated with its infection. METHODOLOGY/PRINCIPAL FINDINGS: The cross-sectional study of the seropositivity of specific antibodies for Toxocara spp. was performed on 280 pregnant women. Serum samples were examined with enzyme-linked immunoassay. Epidemiological data were obtained through a questionnaire containing information about obstetric history, general life style choices, and the social and economic status of the women. The prevalence of Toxocara spp. IgG in pregnant women was 6.4%. Some of the risk factors associated with the infection were owning dogs (p = 0.003), living in the city centre (p = 0.028), living at the city beach (p = 0.003), and having a family income at or below minimum wage (p < 0.001). There was no association between reproductive disorders and Toxocara seropositivity. CONCLUSIONS/SIGNIFICANCE: The seroprevalence of 6.4% for Toxocara spp. in pregnant women shows that there was exposure to the parasite. The study demonstrates the need for attention for the completion of clinical diagnosis parameters, as well as the expansion of highly specific serological studies in different regions to understand the impact of toxocariasis in pregnancy. PMID- 26146835 TI - Comparison of Bacterial Burden and Cytokine Gene Expression in Golden Hamsters in Early Phase of Infection with Two Different Strains of Leptospira interrogans. AB - Leptospirosis, a zoonotic infection with worldwide prevalence, is caused by pathogenic spirochaetes of Leptospira spp., and exhibits an extremely broad clinical spectrum in human patients. Although previous studies indicated that specific serovars or genotypes of Leptospira spp. were associated with severe leptospirosis or its outbreak, the mechanism underlying the difference in virulence of the various Leptospira serotypes or genotypes remains unclear. The present study addresses this question by measuring and comparing bacterial burden and cytokine gene expression in hamsters infected with strains of two L. interrogans serovars Manilae (highly virulent) and Hebdomadis (less virulent). The histopathology of kidney, liver, and lung tissues was also investigated in infected hamsters. A significantly higher bacterial burden was observed in liver tissues of hamsters infected with serovar Manilae than those infected with serovar Hebdomadis (p < 0.01). The average copy number of the leptospiral genome was 1,302 and 20,559 in blood and liver, respectively, of hamsters infected with serovar Manilae and 1,340 and 4,896, respectively, in hamsters infected with serovar Hebdomadis. The expression levels of mip1alpha in blood; tgfbeta, il1beta, mip1alpha, il10, tnfalpha and cox2 in liver; and tgfbeta, il6, tnfalpha and cox2 in lung tissue were significantly higher in hamsters infected with serovar Manilae than those infected with serovar Hebdomadis (p < 0.05). In addition, infection with serovar Manilae resulted in a significantly larger number of hamsters with tnfalpha upregulation (p = 0.04). Severe distortion of tubular cell arrangement and disruption of renal tubules in kidney tissues and hemorrhage in lung tissues were observed in Manilae-infected hamsters. These results demonstrate that serovar Manilae multiplied more efficiently in liver tissues and induced significantly higher expression of genes encoding pro- and anti-inflammatory cytokines than serovar Hebdomadis even in tissues for which a significant difference in leptospiral load was not observed. In addition, our results suggest a serovar Manilae-specific mechanism responsible for inducing severe damage in kidneys and hemorrhage in lung. PMID- 26146836 TI - Pre- and/or Intra-Operative Prescription of Diuretics, but Not Renin-Angiotensin System Inhibitors, Is Significantly Associated with Acute Kidney Injury after Non Cardiac Surgery: A Retrospective Cohort Study. AB - BACKGROUND AND OBJECTIVES: Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This was a retrospective observational study. Inclusion criteria were adult patients (age >= 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine >= 0.3 mg/dL or 150% within 48 hours, or urine output < 0.5 ml/kg/hour for > 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. RESULTS: There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1). CONCLUSIONS: Prescription of diuretics, but not ACE I/ARB, was independently associated with postoperative AKI after non-cardiac surgery, especially in patients with low propensity for diuretic use. It might be reasonable to withhold preoperative diuretics in these patients. PMID- 26146838 TI - On-Demand Indexing for Referential Compression of DNA Sequences. AB - The decreasing costs of genome sequencing is creating a demand for scalable storage and processing tools and techniques to deal with the large amounts of generated data. Referential compression is one of these techniques, in which the similarity between the DNA of organisms of the same or an evolutionary close species is exploited to reduce the storage demands of genome sequences up to 700 times. The general idea is to store in the compressed file only the differences between the to-be-compressed and a well-known reference sequence. In this paper, we propose a method for improving the performance of referential compression by removing the most costly phase of the process, the complete reference indexing. Our approach, called On-Demand Indexing (ODI) compresses human chromosomes five to ten times faster than other state-of-the-art tools (on average), while achieving similar compression ratios. PMID- 26146837 TI - Shear Stress-Induced Alteration of Epithelial Organization in Human Renal Tubular Cells. AB - Tubular epithelial cells in the kidney are continuously exposed to urinary fluid shear stress (FSS) generated by urine movement and recent in vitro studies suggest that changes of FSS could contribute to kidney injury. However it is unclear whether FSS alters the epithelial characteristics of the renal tubule. Here, we evaluated in vitro and in vivo the influence of FSS on epithelial characteristics of renal proximal tubular cells taking the organization of junctional complexes and the presence of the primary cilium as markers of epithelial phenotype. Human tubular cells (HK-2) were subjected to FSS (0.5 Pa) for 48 h. Control cells were maintained under static conditions. Markers of tight junctions (Claudin-2, ZO-1), Par polarity complex (Pard6), adherens junctions (E Cadherin, beta-Catenin) and the primary cilium (alpha-acetylated Tubulin) were analysed by quantitative PCR, Western blot or immunocytochemistry. In response to FSS, Claudin-2 disappeared and ZO-1 displayed punctuated and discontinuous staining in the plasma membrane. Expression of Pard6 was also decreased. Moreover, E-Cadherin abundance was decreased, while its major repressors Snail1 and Snail2 were overexpressed, and beta-Catenin staining was disrupted along the cell periphery. Finally, FSS subjected-cells exhibited disappeared primary cilium. Results were confirmed in vivo in a uninephrectomy (8 months) mouse model where increased FSS induced by adaptive hyperfiltration in remnant kidney was accompanied by both decreased epithelial gene expression including ZO-1, E cadherin and beta-Catenin and disappearance of tubular cilia. In conclusion, these results show that proximal tubular cells lose an important number of their epithelial characteristics after long term exposure to FSS both in vitro and in vivo. Thus, the changes in urinary FSS associated with nephropathies should be considered as potential insults for tubular cells leading to disorganization of the tubular epithelium. PMID- 26146839 TI - Long-Duration Spaceflight Increases Depth Ambiguity of Reversible Perspective Figures. AB - The objective of this study was to investigate depth perception in astronauts during and after spaceflight by studying their sensitivity to reversible perspective figures in which two-dimensional images could elicit two possible depth representations. Other ambiguous figures that did not give rise to a perception of illusory depth were used as controls. Six astronauts and 14 subjects were tested in the laboratory during three sessions for evaluating the variability of their responses in normal gravity. The six astronauts were then tested during four sessions while on board the International Space Station for 5 6 months. They were finally tested immediately after return to Earth and up to one week later. The reaction time decreased throughout the sessions, thus indicating a learning effect. However, the time to first percept reversal and the number of reversals were not different in orbit and after the flight compared to before the flight. On Earth, when watching depth-ambiguous perspective figures, all subjects reported seeing one three-dimensional interpretation more often than the other, i.e. a ratio of about 70-30%. In weightlessness this asymmetry gradually disappeared and after 3 months in orbit both interpretations were seen for the same duration. These results indicate that the perception of "illusory" depth is altered in astronauts during spaceflight. This increased depth ambiguity is attributed to the lack of the gravitational reference and the eye-ground elevation for interpreting perspective depth cues. PMID- 26146840 TI - Effects of Resistance Training on Measures of Muscular Strength in People with Parkinson's Disease: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The aim of this systematic review and meta-analysis was to determine the overall effect of resistance training (RT) on measures of muscular strength in people with Parkinson's disease (PD). METHODS: Controlled trials with parallel group-design were identified from computerized literature searching and citation tracking performed until August 2014. Two reviewers independently screened for eligibility and assessed the quality of the studies using the Cochrane risk-of bias-tool. For each study, mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for continuous outcomes based on between-group comparisons using post-intervention data. Subgroup analysis was conducted based on differences in study design. RESULTS: Nine studies met the inclusion criteria; all had a moderate to high risk of bias. Pooled data showed that knee extension, knee flexion and leg press strength were significantly greater in PD patients who undertook RT compared to control groups with or without interventions. Subgroups were: RT vs. control-without intervention, RT vs. control-with-intervention, RT-with-other-form-of-exercise vs. control-without-intervention, RT-with-other-form-of-exercise vs. control-with intervention. Pooled subgroup analysis showed that RT combined with aerobic/balance/stretching exercise resulted in significantly greater knee extension, knee flexion and leg press strength compared with no-intervention. Compared to treadmill or balance exercise it resulted in greater knee flexion, but not knee extension or leg press strength. RT alone resulted in greater knee extension and flexion strength compared to stretching, but not in greater leg press strength compared to no-intervention. DISCUSSION: Overall, the current evidence suggests that exercise interventions that contain RT may be effective in improving muscular strength in people with PD compared with no exercise. However, depending on muscle group and/or training dose, RT may not be superior to other exercise types. Interventions which combine RT with other exercise may be most effective. Findings should be interpreted with caution due to the relatively high risk of bias of most studies. PMID- 26146842 TI - Flap flexibility amongst plasmepsins I, II, III, IV, and V: Sequence, structural, and molecular dynamics analyses. AB - Herein, for the first time, we comparatively report the opening and closing of apo plasmepsin I - V. Plasmepsins belong the aspartic protease family of enzymes, and are expressed during the various stages of the P. falciparum lifecycle, the species responsible for the most lethal and virulent malaria to infect humans. Plasmepsin I, II, IV and HAP degrade hemoglobin from infected red blood cells, whereas plasmepsin V transport proteins crucial to the survival of the malaria parasite across the endoplasmic reticulum. Flap-structures covering the active site of aspartic proteases (such as HIV protease) are crucial to the conformational flexibility and dynamics of the protein, and ultimately control the binding landscape. The flap-structure in plasmepsins is made up of a flip tip in the N-terminal lying perpendicular to the active site, adjacent to the flexible loop region in the C-terminal. Using molecular dynamics, we propose three parameters to better describe the opening and closing of the flap-structure in apo plasmepsins. Namely, the distance, d1, between the flap tip and the flexible region; the dihedral angle, phi, to account for the twisting motion; and the TriCalpha angle, theta1. Simulations have shown that as the flap-structure twists, the flap and flexible region move apart opening the active site, or move toward each other closing the active site. The data from our study indicate that of all the plasmepsins investigated in the present study, Plm IV and V display the highest conformational flexibility and are more dynamic structures versus Plm I, II, and HAP. PMID- 26146841 TI - Multiple Genetic Modifiers of Bilirubin Metabolism Involvement in Significant Neonatal Hyperbilirubinemia in Patients of Chinese Descent. AB - The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. A case-control study was designed to assess comprehensive contributions of the multiple genetic modifiers of bilirubin metabolism on significant neonatal hyperbilirubinemia in Chinese descendents. Eleven common mutations and polymorphisms across five bilirubin metabolism genes, namely those encoding UGT1A1, HMOX1, BLVRA, SLCO1B1 and SLCO1B3, were determined using the high resolution melt (HRM) assay or PCR-capillary electrophoresis analysis. A total of 129 hyperbilirubinemic infants and 108 control subjects were evaluated. Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of -TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7). In addition, the SLCO1B1 and SLCO1B3 polymorphisms also contributed to an increased risk of hyperbilirubinemia. This detailed analysis revealed the impact of multiple genetic modifiers on neonatal hyperbilirubinemia. This may support the use of genetic tests for clinical risk assessment. Furthermore, the established HRM assay can serve as an effective method for large-scale investigation. PMID- 26146844 TI - Subcutaneous panniculitis-like T-cell lymphoma: Pediatric case series demonstrating heterogeneous presentation and option for watchful waiting. AB - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and primary cutaneous gamma delta T-cell lymphoma (PCGD-TCL) were initially both classified as subcutaneous panniculitis-like T-cell lymphoma. In 2008, SPTCL with alpha-beta T cell receptor subtype was separated from primary cutaneous gamma delta T-cell lymphomas (PCGD-TCL). We report four pediatric cases that demonstrate the heterogeneity of each disease and show that PCGD-TCL in children can have an indolent course, whereas SPTCL can behave aggressively. Three patients had spontaneous, durable remissions without treatment, whereas the one patient with disease progression was treated successfully. Watchful waiting may thus be appropriate for initial management of children. PMID- 26146845 TI - Likelihood of use and perception towards biosimilars in rheumatoid arthritis: a global survey of rheumatologists. PMID- 26146846 TI - Fully Crystalline Faceted Fe-Au Core-Shell Nanoparticles. AB - Fe-Au core-shell nanoparticles displaying an original polyhedral morphology have been successfully synthesized through a physical route. Analyses using transmission electron microscopy show that the Au shell forms truncated pyramids epitaxially grown on the (100) facets of the iron cubic core. The evolution of the elastic energy and strain field in the nanoparticles as a function of their geometry and composition is calculated using the finite-element method. The stability of the remarkable centered core-shell morphology experimentally observed is attributed to the weak elastic energy resulting from the low misfit at the Fe/Au (100) interface compared to the surface energy contribution. PMID- 26146847 TI - Hydrostable and Nitryl/Methyl-Functionalized Metal-Organic Framework for Drug Delivery and Highly Selective CO2 Adsorption. AB - By using a strategy of introducing hydrophobic groups to the linkers, a hydrostable MOF was constructed based on 5-nitroisophthalate and 2,2'-dimethyl 4,4'-bipyridine coligands, revealing a 3D dia topology structure with a 1D channel parallel to the c axis. TGA, PXRD, and water vapor sorption results show high thermal and water stability for the framework. The framework is very porous and possesses not only high busulfan payloads with an encapsulation efficiency up to 21.5% (17.2 wt %) but also very high CO2 selective capture compared with that of other small gases (i.e., CH4, N2, O2, CO, and H2) at 298 K based on molecular simulations due to the pore surface being populated by methyl and nitryl groups. Furthermore, in vitro MTT assays were conducted on four different cells lines with increasing concentrations of the framework, and the results showed that the framework was nontoxic (cell viability >80%) in spite of the concentrations up to 500 MUg/mL. PMID- 26146848 TI - Nonlinear Optical Properties of Fluorescent Dyes Allow for Accurate Determination of Their Molecular Orientations in Phospholipid Membranes. AB - Several methods based on single- and two-photon fluorescence detected linear dichroism have recently been used to determine the orientational distributions of fluorescent dyes in lipid membranes. However, these determinations relied on simplified descriptions of nonlinear anisotropic properties of the dye molecules, using a transition dipole-moment-like vector instead of an absorptivity tensor. To investigate the validity of the vector approximation, we have now carried out a combination of computer simulations and polarization microscopy experiments on two representative fluorescent dyes (DiI and F2N12S) embedded in aqueous phosphatidylcholine bilayers. Our results indicate that a simplified vector-like treatment of the two-photon transition tensor is applicable for molecular geometries sampled in the membrane at ambient conditions. Furthermore, our results allow evaluation of several distinct polarization microscopy techniques. In combination, our results point to a robust and accurate experimental and computational treatment of orientational distributions of DiI, F2N12S, and related dyes (including Cy3, Cy5, and others), with implications to monitoring physiologically relevant processes in cellular membranes in a novel way. PMID- 26146849 TI - In Cell Footprinting Coupled with Mass Spectrometry for the Structural Analysis of Proteins in Live Cells. AB - Protein footprinting coupled with mass spectrometry has become a widely used tool for the study of protein-protein and protein-ligand interactions and protein conformational change. These methods provide residue-level analysis on protein interaction sites and have been successful in studying proteins in vitro. The extension of these methods for in cell footprinting would open an avenue to study proteins that are not amenable for in vitro studies and would probe proteins in their native environment. Here we describe the application of an oxidative-based footprinting approach inside cells in which hydroxyl radicals are used to oxidatively modify proteins. Mass spectrometry is used to detect modification sites and to calculate modification levels. The method is probing biologically relevant proteins in live cells, and proteins in various cellular compartments can be oxdiatively modified. Several different amino acid residues are modified making the method a general labeling strategy for the study of a variety of proteins. Further, comparison of the extent of oxidative modification with solvent accessible surface area reveals the method successfully probes solvent accessibility. This marks the first time protein footprinting has been performed in live cells. PMID- 26146850 TI - Electrostatic Polyion Micelles with Fluorescence and MRI Dual Functions. AB - We report in this work the formation of fluorescence and MRI bimodal imaging nanoparticles achieved by electrostatic self-assembly. The nanoparticles are micelles formed with Gd(3+) ion, a bisligand that contains aggregation induced emission (AIE) group, and a block copolymer. The coordination between the Gd(3+) ion and the bisligand produces a negatively charged coordination complex, which interacted with the positive-neutral block copolymer to form polyion micelles. The micelles exhibit considerable fluorescence owing to the rotation restriction of the AIE group; meanwhile, the longitudinal relaxation of water was significantly slowed down which provide T1 contrast for magnetic resonance imaging. In vitro fluorescence imaging and in vivo MRI measurements verified this micelle indeed exhibit dual imaging ability. We expect that this orthogonal imaging may provide more accurate diagnosis in practical applications and will pave the way for the development of an advanced technique for diagnosis. PMID- 26146851 TI - Silver Nanowire-Conducting Polymer-ITO Hybrids for Flexible and Transparent Conductive Electrodes with Excellent Durability. AB - Solution-processed silver nanowire (AgNW) films have attracted attention as transparent and conductive electrodes for flexible optoelectronic devices and touch screens, to replace sputtered indium-tin-oxide (ITO) films. However, the mechanical flexibility, environmental durability, and the optical (such as transparency and a haze) and electrical properties of the AgNW films should be improved for their practical application. In this work, high-performance and roll to-roll processed AgNW-based hybrid electrodes comprising poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) and/or ITO are introduced. The optical and electrical properties of the AgNW films combined with PEDOT: PSS, ITO, or both of them were systematically examined. Among the films, the AgNW-PEDOT:PSS-ITO hybrid film exhibits a high transmittance (88%) and a low sheet resistance (44 Omega sq(-1)) with a small haze (1.9%). Moreover, the hybrid films show excellent durability to a variety of environmental stresses. By virtues of the high performance and durability, it is believed that the AgNW PEDOT:PSS-ITO hybrid electrodes are highly suitable for practical use. PMID- 26146852 TI - Theory of mind in Alzheimer disease: Evidence of authentic impairment during social interaction. AB - OBJECTIVE: The present study aimed to investigate theory of mind (the ability to infer others' mental states) deficit in 20 patients with mild Alzheimer's disease and 20 healthy controls, with 2 theory of mind tasks, 1 of them being a real interactive task. Previous results concerning preserved or altered theory of mind abilities in Alzheimer's disease have been inconsistent and relationships with other cognitive dysfunctions (notably episodic memory and executive functions) are still unclear. METHOD: The first task we used was a false belief paradigm as frequently used in literature whereas the second task, a referential communication task, assessed theory of mind in a real situation of interaction. Participants also underwent neuropsychological evaluation to investigate potential relationships between theory of mind and memory deficits. RESULTS: The results showed that Alzheimer patients presented a genuine and significant theory of mind deficit compared to control participants characterized notably by difficulties to attribute knowledge to an interlocutor in a real social interaction. CONCLUSION: These results further confirm that theory of mind is altered in early stages of Alzheimer dementia which is consistent with previous works. More specifically, this study is the first to objectivize this impairment in social interaction. PMID- 26146853 TI - Asynchrony in executive networks predicts cognitive slowing in multiple sclerosis. AB - OBJECTIVE: Cognitive slowing is a core neuropsychological symptom of Multiple Sclerosis (MS). We aimed to assess the extent to which cognitive slowing in MS was predicted by changes in dorsolateral prefrontal networks. METHOD: We assessed patients with relapsing-remitting MS and healthy controls (HCs) on measures of processing speed. Participants underwent a functional MRI while performing a processing speed task to allow assessment of task-based connectivity. RESULTS: Patients were slower than HCs on the processing speed tasks. Patients showed attenuated connectivity between right and left dorsolateral prefrontal cortex (DLPFC) and task-relevant brain regions compared to HCs during processing speed task performance. Patients' connectivity with DLPFC in these group-disparate networks accounted for significant variability in their performance on processing speed measures administered both in and out of the imaging environment. Specifically, patients who had stronger functional connections with DLPFC in group-disparate networks performed faster than patients with weaker connections with DLPFC in group-disparate networks. CONCLUSION: Results suggest that MS related cognitive slowing can be accounted for by systemic alterations in executive functional networks. PMID- 26146854 TI - Neurocognitive and neurophysiological correlates of motor planning during familiar and novel contexts. AB - OBJECTIVE: Research suggests that behavioral indices of motor planning (i.e., latencies that precede motor output) (a) relate to processing speed (PS) and executive functioning (EF), but not working memory (WM), and (b) deteriorate in novel contexts. It is not clear whether an electrophysiological index of motor planning (i.e., movement-related cortical potentials; MRCPs) also relates to PS and EF, and whether it deteriorates in novel contexts. This study sought to clarify associations among these variables while manipulating contextual novelty. METHOD: Forty healthy adults completed standardized measures of PS, EF, and WM. Participants performed highly familiar motor sequences in familiar versus novel contexts during EEG recording, while motor planning latencies and peak MRCPs were obtained. Hierarchical regressions assessed the relative contributions of PS, EF, and WM to motor planning latencies and MRCPs. RESULTS: Novel contexts elicited longer planning latencies (gav = 1.96) and reduced MRCPs (gav = .24) compared to familiar contexts. PS predicted planning times in both familiar (R2 = .12) and novel contexts (R2 = .15), while EF contributed additional variance during novel contexts only (R2 Change = .10). EF was the sole predictor of MRCPs in both familiar (R2 = .12) and novel contexts (R2 = .18). WM did not predict planning latencies or MRCPs. CONCLUSIONS: Contextual novelty alone can decrease performance and neural activation during complex sequencing. The general link between preparatory activation and EF suggests that capacity limitations drive novelty effects, and implies a common substrate underlying motor planning and higher-order behavioral control. PMID- 26146855 TI - Prevalence of anxiety following adult traumatic brain injury: A meta-analysis comparing measures, samples and postinjury intervals. AB - OBJECTIVE: Anxiety following a traumatic brain injury (TBI) is a common problem; however, disparate prevalence estimates limit the clinical utility of research. The purpose of the current study was to examine how differences in methodological variables and sample characteristics impact on the prevalence of anxiety. METHOD: Data from 41 studies that examined either the prevalence of generalized anxiety disorder (GAD) diagnoses or clinically significant "cases" of self-reported anxiety following adult, nonpenetrating TBI were analyzed, and the impact of diagnostic criteria, measure, postinjury interval and injury severity was evaluated. RESULTS: Overall, 11% of people were diagnosed with GAD and 37% reported clinically significant levels of anxiety following TBI. Prevalence estimates varied for different diagnostic criteria (range: 2%-19%), interview schedules (range: 2%-28%), and self-report measures (range: 36%-50%). GAD and "cases" of anxiety were most prevalent 2 to 5 years postinjury. The rates of GAD increased with injury severity (mild: 11%, severe 15%), but "cases" decreased (mild: 53%, severe: 38%), although neither difference was significant. CONCLUSIONS: Anxiety is common after a TBI and ongoing monitoring and treatment should be provided. Methodological and sample characteristics should be clear and well-defined, as differences across studies (e.g., how anxiety is conceptualized, which measure is used, time since injury, injury severity) impact prevalence rates. PMID- 26146856 TI - Lack of global precedence and global-to-local interference without local processing deficit: A robust finding in children with attention deficit/hyperactivity disorder under different visual angles of the Navon task. AB - OBJECTIVE: The Navon effect (Navon, 1977) is an automatic tendency to process the global picture prior to local details when processing compound patterns. However, several recent studies have reported that this effect is lacking in attention deficit/hyperactivity disorder (ADHD). Although previous research has shown that the Navon effect is strongly affected by visual angles, whether this phenomenon will also be observed in ADHD is yet to be understood. We examine the lack of the Navon effect in ADHD under various visual angles to ensure that this phenomenon is not an artifact of saliency. METHOD: By employing three different visual angles for the local stimuli, global and local processing of Navon-type hierarchical letters was examined in participants with ADHD (n = 15) and a comparison group (n = 17). RESULTS: ADHD participants presented with a lack of the Navon effect without local processing deficit regardless of visual angle, in comparison to non-ADHD participants. CONCLUSION: A lack of global precedence and global-to-local interference without local processing deficit can be generalized in ADHD. This suggests that people with ADHD experience difficulties in processing the "whole picture," and it also challenges the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; American Psychiatric Association, 2013) criteria of ADHD in which the failure to pay close attention to details was emphasized. Moreover, the current results have important implications for understanding ADHD and could also have significant clinical value. PMID- 26146857 TI - Unique case of orbital 'progressive transformation of the germinal centre'-type immunoglobulin-G4 disease with a heralding lesion in the inguinal lymph nodes. PMID- 26146858 TI - Retinal vascular and structural dynamics during acute hyperglycaemia. AB - PURPOSE: To compare retinal vascular dynamics during acute hyperglycaemia in patients with type 2 diabetes and healthy volunteers. METHODS: Twenty-one patients with type 2 diabetes and 27 healthy controls were examined with fundus photographic measurement of retinal vessel diameters, retinal oximetry, macular perfusion velocities and optical coherence tomographic measurement of subfoveal choroidal thickness every 30 min during a 3-hr 75 g oral glucose tolerance test (OGTT). Patients paused antidiabetic therapy for 1 week prior to the OGTT. RESULTS: Plasma glucose (PG) and fluctuations in PG were larger in patients with diabetes (p < 0.0001). PG increased significantly 30 min after ingestion of glucose (p < 0.0001 in both groups). With a delay of 0-120 min, the PG increase was followed by increased retinal arterial oxygen saturations and arteriovenous oxygen saturation differences, narrowed retinal veins and increased arteriovenous diameter ratios. No effect of age, gender or diabetes status was observed. Choroidal thickness was transiently reduced in controls and unchanged in patients with diabetes (p = 0.021). Macular perfusion velocities increased after 150 min in patients with diabetes but not in controls (arterial p = 0.059; venous p = 0.16). Higher age and diabetes tended to be associated with higher retinal arterial oxygen saturation. CONCLUSION: The transition from fasting to acute hyperglycaemia is followed, with a delay of up to 2 hr, by retinal vascular changes, notably increased oxygen extraction, suggesting an effect of secondary metabolic changes. Retinal responses were similar in patients with type 2 diabetes and controls despite differences in glucose levels. It is necessary to standardize measurement conditions in studies of retinal physiology. PMID- 26146860 TI - Immunity, Inflammation, and Prehypertension: In What Order? PMID- 26146859 TI - Chronic Binge Alcohol Administration Increases Intestinal T-Cell Proliferation and Turnover in Rhesus Macaques. AB - BACKGROUND: Alcohol use results in changes in intestinal epithelial cell turnover and microbial translocation, yet less is known about the consequences on intestinal lymphocytes in the gut. Here, we compared T-cell subsets in the intestine of macaques before and after 3 months of chronic alcohol administration to examine the effects of alcohol on intestinal T-cell subsets. METHODS: Rhesus macaques received either alcohol or isocaloric sucrose as a control treatment daily over a 3-month period via indwelling gastric catheters. Intestinal lymphocyte subsets were identified in biopsy samples by flow cytometry. Twenty four hours prior to sampling, animals were inoculated with bromo-deoxyuridine (BrdU) to assess lymphocyte proliferation. Immunohistochemistry was performed on tissue samples to quantitate CD3+ cells. RESULTS: Animals receiving alcohol had increased rates of intestinal T-cell turnover of both CD4+ and CD8+ T cells as reflected by increased BrdU incorporation. However, absolute numbers of T cells were decreased in intestinal tissues as evidenced by immunohistochemistry for total CD3 expression per mm(2) intestinal lamina propria in tissue sections. Combining immunohistochemistry and flow cytometry data showed that the absolute numbers of CD8+ T cells were significantly decreased, whereas absolute numbers of total CD4+ T cells were minimally decreased. CONCLUSIONS: Collectively, these data indicate that alcohol exposure to the small intestine results in marked loss of CD3+ T cells, accompanied by marked increases in CD4+ and CD8+ T-cell proliferation and turnover, which we speculate is an attempt to maintain stable numbers of T cells in tissues. This suggests that alcohol results in accelerated T-cell turnover in the gut, which may contribute to premature T-cell senescence. Further, these data indicate that chronic alcohol administration results in increased levels of HIV target cells (proliferating CD4+ T cells) that may support higher levels of HIV replication in intestinal tissues. PMID- 26146861 TI - Anatomy and Physiology of Left Ventricular Suction Induced by Rotary Blood Pumps. AB - This study in five large greyhound dogs implanted with a VentrAssist left ventricular assist device focused on identification of the precise site and physiological changes induced by or underlying the complication of left ventricular suction. Pressure sensors were placed in left and right atria, proximal and distal left ventricle, and proximal aorta while dual perivascular and tubing ultrasonic flow meters measured blood flow in the aortic root and pump outlet cannula. When suction occurred, end-systolic pressure gradients between proximal and distal regions of the left ventricle on the order of 40-160 mm Hg indicated an occlusive process of variable intensity in the distal ventricle. A variable negative flow difference between end systole and end diastole (0.5-3.4 L/min) was observed. This was presumably mediated by variable apposition of the free and septal walls of the ventricle at the pump inlet cannula orifice which lasted approximately 100 ms. This apposition, by inducing an end-systolic flow deficit, terminated the suction process by relieving the imbalance between pump requirement and delivery from the right ventricle. Immediately preceding this event, however, unnaturally low end-systolic pressures occurred in the left atrium and proximal left ventricle which in four dogs lasted for 80-120 ms. In one dog, however, this collapse progressed to a new level and remained at approximately -5 mm Hg across four heart beats at which point suction was relieved by manual reduction in pump speed. Because these pressures were associated with a pulmonary capillary wedge pressure of -5 mm Hg as well, they indicate total collapse of the entire pulmonary venous system, left atrium, and left ventricle which persisted until pump flow requirement was relieved by reducing pump speed. We suggest that this collapse caused the whole vascular region from pulmonary capillaries to distal left ventricle to behave as a Starling resistance which further reduced right ventricular output thus contributing to a major reduction in pump flow. We contend that similar complications of manual speed control also occur in the human subject and remain a major unsolved problem in the clinical management of patients implanted with rotary blood pumps. PMID- 26146862 TI - Spread of introduced viruses to new plants in natural ecosystems and the threat this poses to plant biodiversity. PMID- 26146863 TI - Virological efficacy with first-line antiretroviral treatment in India: predictors of viral failure and evidence of viral resuppression. AB - OBJECTIVE: Combination antiretroviral therapy (ART) has improved in efficacy, durability and tolerability. Virological efficacy studies in India are limited. We determined incidence and predictors of virological failure among patients initiating first-line ART and described virological resuppression after confirmed failure, with the goal of informing national policy. METHODS: Therapy-naive patients initiated on first-line ART as per national guidelines were monitored every 3 months for adherence and virological response over 2 years. Genotyping on baseline samples was performed to assess primary drug resistance. Multivariate Cox regression analysis was used to assess predictors of virological failure. RESULTS: Virological failure rate among 599 eligible patients was 10.7 failures per 100 person-years. Cumulative failure incidence was 13.2% in the first year and 16.5% over 2 years. Patients initiated on tenofovir had a significantly lower rate of virological failure than those on stavudine or zidovudine (6.7 vs. 11.9 failures per 100 person-years, P = 0.013). Virological failure was independently associated with age <40 years, mean adherence <95%, non-tenofovir-containing regimens and presence of primary drug resistance. In a subset of 311 patients who were reassessed after treatment failure, 19% (11/58) patients resuppressed their viral load to <400 copies/ml after confirmed virological failure. CONCLUSIONS: Our results support the inclusion of tenofovir as first-line ART in resource limited settings and a role for regular adherence counselling and virological monitoring for enhanced treatment success. Detection of early virological failure should provide an opportunity to augment adherence counselling and repeat viral load testing before therapy switch is considered. PMID- 26146864 TI - A patient with a large intrathoracic malignant schwannoma who showed a complete clinical response to rAd-p53-combined with radiotherapy. AB - The prognosis of postoperatively recurred malignant schwannoma is poor and there is no effective treatment. We had a patient who was found to have a large intrathoracic tumor 1 year after surgery and could not tolerate an operation for the second time. We then decided to evaluate the synergistic effect of recombinant adenovirus-p53 (rAd-p53) combined with radiotherapy for the patient. rAd-p53 was injected intratumorally twice a week before radiotherapy, a total of 10 times, over a course of treatment. Radiotherapy then followed gene therapy at five fractions a week for 5 weeks, with a total dosage of 80.6 Gy/31f in the center part of the tumor and 62 Gy/31f in other locations. The pathological diagnosis of malignant schwannoma indicated that the p53 expression was strongly positive and vascular endothelial growth factor and Bcl-2 were positive before treatment on protein immunohistochemical staining. After treatment, the diameter of the tumor was noticeably reduced and the center part of the tumor presented as a fluid anechoic area and cavities on computed tomographic scanning. The result of the puncture biopsy showed that there were many fibronecrotic tissues and no significant tumor cells. The p53 expression was weakly positive, Vascular endothelial growth factor was negative, and Bcl-2 was weakly positive after treatment on protein immunohistochemical staining. PMID- 26146865 TI - An investigation of accessory canals in primary molars - an analytical study. AB - AIM: To evaluate the number, anatomical morphology and patency of accessory canals in the furcation of carious primary molar teeth and to ascertain whether these anatomic variations contribute to endodontic infection. DESIGN: The accessory canals were observed under radiovisiography or RVG (Phase 1), scanning electron microscopy or SEM (Phase 2) and light microscopy (Phase 3). RESULTS: The prevalence of accessory canals was 34.3% with a mean +/- SD of 0.73 +/- 0.980 in Phase 1, 73.3% with a mean +/- SD of 3.07 +/- 3.151 in Phase 2 and 64.3% with a mean +/- SD of 1.68 +/- 2.405 in Phase 3. The results observed were Phase 1 vs Phase 2<0.001 (highly significant), Phase 1 vs Phase 3 0.110 (ns) and Phase 2 vs Phase 3<0.001 (highly significant) employing Wilcoxon signed-rank test. The canals were predominantly oval in shape and ranged from 1 MU to 225 MU in diameter. Only 7% canals were observed to be patent. CONCLUSIONS: Accessory canals may not be the primary cause of transmission of infection in the inter radicular area of primary molars. Other factors enhancing permeability of the pulpal floor may be of more significance and need evaluation on a larger scale. PMID- 26146867 TI - Angiomyxomatous tumor of the falx cerebri. PMID- 26146866 TI - Escherichia coli heme oxygenase modulates host innate immune responses. AB - Induction of mammalian heme oxygenase (HO)-1 and exposure of animals to carbon monoxide (CO) ameliorates experimental colitis. When enteric bacteria, including Escherichia coli, are exposed to low iron conditions, they express an HO-like enzyme, chuS, and metabolize heme into iron, biliverdin and CO. Given the abundance of enteric bacteria residing in the intestinal lumen, our postulate was that commensal intestinal bacteria may be a significant source of CO and those that express chuS and other Ho-like molecules suppress inflammatory immune responses through release of CO. According to real-time PCR, exposure of mice to CO results in changes in enteric bacterial composition and increases E. coli 16S and chuS DNA. Moreover, the severity of experimental colitis correlates positively with E. coli chuS expression in IL-10 deficient mice. To explore functional roles, E. coli were genetically modified to overexpress chuS or the chuS gene was deleted. Co-culture of chuS-overexpressing E. coli with bone marrow derived macrophages resulted in less IL-12p40 and greater IL-10 secretion than in wild-type or chuS-deficient E. coli. Mice infected with chuS-overexpressing E. coli have more hepatic CO and less serum IL-12 p40 than mice infected with chuS deficient E. coli. Thus, CO alters the composition of the commensal intestinal microbiota and expands populations of E. coli that harbor the chuS gene. These bacteria are capable of attenuating innate immune responses through expression of chuS. Bacterial HO-like molecules and bacteria-derived CO may represent novel targets for therapeutic intervention in inflammatory conditions. PMID- 26146868 TI - Resveratrol prevents cadmium activation of Erk1/2 and JNK pathways from neuronal cell death via protein phosphatases 2A and 5. AB - Cadmium (Cd), a toxic environmental contaminant, induces neurodegenerative disorders. Resveratrol, a natural product, has been found to exert neuroprotective effects. However, little is known regarding the effect of resveratrol on Cd-evoked neurotoxicity. Here, we show that resveratrol effectively reversed Cd-elicited cell viability reduction, morphological change, nuclear fragmentation and condensation, as well as activation of caspase-3 in neuronal cells, implying neuroprotection against Cd-poisoning by resveratrol. Further research revealed that both c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases 1/2 (Erk1/2) were involved in the inhibitory effect of resveratrol on Cd-induced cell death, as selective inhibitors of Erk1/2 (U0126) and JNK (SP600125), or over-expression of dominant negative mitogen-activated protein kinase kinase 1 (MKK1) or dominant negative c Jun potentiated resveratrol's prevention of Cd-induced phosphorylation of JNK and Erk1/2, as well as cell death in neuronal cells. Interestingly, resveratrol potently rescued the cells from Cd-induced suppression of protein phosphatases 2A (PP2A) and 5 (PP5) activity. Over-expression of PP2A or PP5 strengthened the inhibitory effects of resveratrol on Cd-induced activation of Erk1/2 and/or JNK, as well as cell death. The results indicate that resveratrol prevents Cd-induced activation of Erk1/2 and JNK pathways and neuronal cell death in part via activating PP2A and PP5. Our findings strongly support the notion that resveratrol may serve as a potential therapeutic agent in the prevention of Cd induced neurodegenerative diseases. PMID- 26146869 TI - Respiratory Motion-Resolved Compressed Sensing Reconstruction of Free-Breathing Radial Acquisition for Dynamic Liver Magnetic Resonance Imaging. AB - OBJECTIVE: This study aimed to demonstrate feasibility of free-breathing radial acquisition with respiratory motion-resolved compressed sensing reconstruction [extra-dimensional golden-angle radial sparse parallel imaging (XD-GRASP)] for multiphase dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced liver imaging, and to compare image quality to compressed sensing reconstruction with respiratory motion-averaging (GRASP) and prior conventional breath-held Cartesian-sampled data sets [BH volume interpolated breath-hold examination (VIBE)] in same patients. SUBJECTS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, 16 subjects underwent free-breathing continuous radial acquisition during Gd-EOB DTPA injection and had prior BH-VIBE available. Acquired data were reconstructed using motion-averaging GRASP approach in which consecutive 84 spokes were grouped in each contrast-enhanced phase for a temporal resolution of approximately 14 seconds. Additionally, respiratory motion-resolved reconstruction was performed from the same k-space data by sorting each contrast-enhanced phase into multiple respiratory motion states using compressed sensing algorithm named XD-GRASP, which exploits sparsity along both the contrast-enhancement and respiratory-state dimensions.Contrast-enhanced dynamic multiphase XD-GRASP, GRASP, and BH-VIBE images were anonymized, pooled together in a random order, and presented to 2 board-certified radiologists for independent evaluation of image quality, with higher score indicating more optimal examination. RESULTS: The XD-GRASP reconstructions had significantly (all P < 0.05) higher overall image quality scores compared to GRASP for early arterial (reader 1: 4.3 +/- 0.6 vs 3.31 +/- 0.6; reader 2: 3.81 +/- 0.8 vs 3.38 +/- 0.9) and late arterial (reader 1: 4.5 +/- 0.6 vs 3.63 +/- 0.6; reader 2: 3.56 +/- 0.5 vs 2.88 +/- 0.7) phases of enhancement for both readers. The XD-GRASP also had higher overall image quality score in portal venous phase, which was significant for reader 1 (4.44 +/- 0.5 vs 3.75 +/- 0.8; P = 0.002). In addition, the XD-GRASP had higher overall image quality score compared to BH-VIBE for early (reader 1: 4.3 +/- 0.6 vs 3.88 +/- 0.6; reader 2: 3.81 +/- 0.8 vs 3.50 +/- 1.0) and late (reader 1: 4.5 +/- 0.6 vs 3.44 +/- 0.6; reader 2: 3.56 +/- 0.5 vs 2.94 +/- 0.9) arterial phases. CONCLUSION: Free-breathing motion-resolved XD-GRASP reconstructions provide diagnostic high-quality multiphase images in patients undergoing Gd-EOB-DTPA enhanced liver examination. PMID- 26146870 TI - Diffusion-Weighted Imaging of the Prostate: Image Quality and Geometric Distortion of Readout-Segmented Versus Selective-Excitation Accelerated Acquisitions. AB - OBJECTIVE: To compare image quality and geometric distortion between readout segmented diffusion-weighted imaging (rs-DWI) and selective-excitation accelerated reduced-field of view (FOV) DWI (sTX-DWI) of the prostate. MATERIALS AND METHODS: Sixty-five patients underwent 3-T MRI of the prostate including rs DWI and sTX-DWI (b values, 0, 50, and 1000 seconds/mm2; FOV, 150 * 150 mm2 and 77 *150 mm for rs-DWI and sTX-DWI; slice thickness, 3 mm; acquisition time, 8:18 min and 1:37 min for rs-DWI and sTX-DWI). Two readers evaluated aspects of image quality and geometric distortion on a 5-point Likert scale. Quantitative analysis of geometric distortion was assessed by measurements of anteroposterior and left right diameters and compared to T2-weighted turbo-spin echo sequence using intraclass correlation coefficient (ICC). RESULTS: There was no significant difference in resolution, capsule demarcation, and zonal anatomy (P = 0.111 0.866). Overall image quality was rated "above average" by reader 1 (4.09 +/- 0.66 and 4.03 +/- 0.79; P = 0.433) and reader 2 (3.86 +/- 0.66 and 3.80 +/- 0.74; P = 0.465) for rs-DWI and sTX-DWI. Reader 1 (0.74 +/- 0.67 and 1.17 +/- 0.84; P < 0.001) and reader 2 (0.55 +/- 0.64 and 1.09 +/- 0.95; P < 0.001) rated the level of geometric distortion significantly lower for rs-DWI than sTX-DWI. Readout segmented DWI (0.9 +/- 2.2 mm) and sTX-DWI (2.1 +/- 3.8 mm) overestimated the anteroposterior diameter of the prostate compared to T2-weighted turbo-spin echo sequence (P < 0.001), the difference being more pronounced for sTX-DWI [ICC, 0.89 (95% confidence interval, 0.83-0.93)] compared to rs-DWI [ICC, 0.96 (95% confidence interval, 0.94-0.96)]. CONCLUSION: Selective-excitation accelerated reduced-FOV DW images (sTX-DWI) of the prostate can be acquired more than 5 times faster than rs-DWI with comparable image quality, at the expense of significantly increased geometric distortion. PMID- 26146871 TI - Persistent Pure Ground-Glass Nodules Larger Than 5 mm: Differentiation of Invasive Pulmonary Adenocarcinomas From Preinvasive Lesions or Minimally Invasive Adenocarcinomas Using Texture Analysis. AB - OBJECTIVE: To evaluate the differentiating potentials of computed tomography texture analysis for invasive pulmonary adenocarcinomas (IPAs) from their preinvasive lesions or minimally invasive adenocarcinomas (MIAs) manifesting as persistent pure ground-glass nodules (PGGNs) larger than 5 mm. MATERIALS AND METHODS: This institutional review board-approved retrospective study included 63 patients (23 men and 40 women) with 66 PGGNs larger than 5 mm on unenhanced computed tomography from 2005 to 2013. All PGGNs were pathologically confirmed and categorized into 2 groups [IPAs (n = 11) vs preinvasive lesions (n = 41)/MIAs (n = 14)]. Each PGGN was segmented manually, and their texture features were quantitatively extracted. To identify significant differentiating factors of IPAs from preinvasive lesions/MIAs, multivariate logistic regression and C-statistic analyses were performed. RESULTS: Between IPAs and preinvasive lesions/MIAs, nodule size, volume, mass, entropy, effective diameter, and surface area were significantly different (P < 0.05), and homogeneity and gray level co-occurrence matrix inverse difference moment showed marginal significance (P < 0.10). Subsequent multivariate analysis revealed larger nodule mass [adjusted odds ratio (OR), 11.92], higher entropy (adjusted OR, 35.12), and lower homogeneity (adjusted OR, 0.278 * 10) as independent differentiating factors of IPAs. Subgroup analysis showed that larger nodule mass, higher entropy, and lower homogeneity were also significant differentiating variables of IPAs in nodules of diameter 10 mm or larger. A multiple logistic regression model using these features showed excellent [area under the curve (AUC), 0.962] and significantly higher differentiating performance compared to nodule size (AUC, 0.712) or mass (AUC, 0.788) alone. CONCLUSION: Computed tomography texture features such as higher entropy and lower homogeneity were significant differentiating factors of IPAs presenting as PGGNs larger than 5 mm and have potentials to enhance the differentiating performance. PMID- 26146872 TI - Functional Proton MRI in Emphysematous Rats. AB - OBJECTIVE: To demonstrate the feasibility of proton magnetic resonance imaging (MRI) ventilation-related maps in rodents for the evaluation of lung function in the presence of pancreatic porcine elastase (PPE)-induced emphysema. MATERIALS AND METHODS: Twelve rats were equally divided into 3 groups: group 1 (no administration of PPE); group 2 (PPE selectively only in the left lung); and group 3 (PPE administered in both lungs). Magnetic resonance imaging (MRI) and computed tomographic (CT) data were acquired at baseline, at 2 weeks and 4 weeks after administration, after which the animals were euthanized. The MRI protocol comprised a golden angle 2-dimensional ultrashort echo time MRI sequence [echo time, 0.343 millisecond (ms); repetition time, 120 ms; 12 slides with thickness, 1 mm; acquisition time, 30 minutes], from which inspiration and expiration images were reconstructed after the extraction of a self-gating signal. Inspiration images were registered to images at expiration, and expansion maps were created by calculating the specific difference in signal intensity. The lungs were segmented, and the mean specific expansion (MSE) calculated as an established surrogate for fractional ventilation. Computed tomographic data provided lung density (peak of the Hounsfield unit histogram, HU_P), whereas histology provided the mean linear intercept for each lung. RESULTS: Two weeks after administration, the control group had a mean MSE in both lungs corresponding to 96% of the baseline. Group 2 had 85% of the baseline, and group 3 had 57%. Considering the PPE-treated lungs alone, a significant reduction in MSE of 27% at 2 weeks and 40% at 4 weeks was found with respect to nontreated lungs. Significant correlations between HU_P and MSE were found at all time points (baseline: r = 0.606, P = 0.0017; 2 weeks: r = 0.837, P <= 0.0001; 4 weeks: r = 0.765, P < 0.0001; all time points: r = 0.739, P < 0.0001). Mean linear intercept values significantly correlated both with MRI MSE (r = -0.770, P < 0.0001) and with CT HU_P (r = 0.882, P < 0.0001). DISCUSSION: The calculated ventilation-related maps showed a reduction of function in the PPE-treated lungs, both compared to the nontreated lungs and to the baseline values. Moreover, a good agreement between MRI-measured MSE, CT, and histology data quantitatively supports the presence of ventilation deficit in emphysematous lungs.In this work, we have demonstrated the feasibility of ventilation-related maps from non-contrast-enhanced H lung MRI, which were capable of tracking changes in lung function over time in emphysematous rats. PMID- 26146873 TI - Ashy dermatosis (erythema dyschromicum perstans) induced by omeprazole: a report of three cases. PMID- 26146875 TI - Increases in multiple psychiatric disorders in parents and grandparents of patients with bipolar disorder from the USA compared with The Netherlands and Germany. AB - OBJECTIVE: We previously found that compared with Europe more parents of the USA patients were positive for a mood disorder, and that this was associated with early onset bipolar disorder. Here we examine family history of psychiatric illness in more detail across several generations. METHODS: A total of 968 outpatients (average age 41) with bipolar disorder from four sites in the USA and three in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic and family history information on a patient questionnaire. Family history of psychiatric illness (bipolar disorder, unipolar depression, suicide attempt, alcohol abuse, substance abuse, and other illness) was collected for each parent, four grandparents, siblings, and children. RESULTS: Parents of the probands with bipolar disorder from the USA compared with Europe had a significantly higher incidence of both unipolar and bipolar mood disorders, as well as each of the other psychiatric conditions listed above. With a few exceptions, this burden of psychiatric disorders was also significantly greater in the grandparents, siblings, and children of the USA versus European patients. CONCLUSION: The increased complexity of psychiatric illness and its occurrence over several generations in the families of patients with bipolar disorder from the USA versus Europe could be contributing to the higher incidence of childhood onsets and greater virulence of illness in the USA compared with Europe. These data are convergent with others suggesting increased both genetic and environmental risk in the USA, but require replication in epidemiologically-derived populations with data based on interviews of the family members. PMID- 26146876 TI - Maternal Mild Thyroid Hormone Insufficiency in Early Pregnancy and Attention Deficit/Hyperactivity Disorder Symptoms in Children. AB - IMPORTANCE: Maternal thyroid hormone insufficiency during pregnancy can affect children's cognitive development. Nevertheless, the behavioral outcomes of children exposed prenatally to mild thyroid hormone insufficiency are understudied. OBJECTIVE: To examine whether exposure to maternal mild thyroid hormone insufficiency in early pregnancy was related to symptoms of attention deficit/hyperactivity disorder (ADHD) in children at 8 years of age. DESIGN, SETTING, AND PARTICIPANTS: The study was embedded within the Generation R, a population-based birth cohort in the Netherlands. Children in the Generation R Study are followed up from birth (April 1, 2002, through January 31, 2006) until young adulthood. Of the 4997 eligible mother-child pairs with data on maternal thyroid levels (excluding twins), 3873 pairs of children and caregivers (77.5%) visited the Generation R research center for in-depth assessments and were included in the main analyses. Data collection in Generation R started December 1, 2001 (enrollment of pregnant women), and is ongoing. For this study, we used the data that were collected until January 1, 2014. Data analyses started on January 31 and finished June 30, 2014. MAIN OUTCOMES AND MEASURES: Maternal hypothyroxinemia, characterized by low levels of free thyroxine coexisting with reference thyrotropin levels, and children's symptoms of ADHD. Maternal thyroid hormone levels (thyrotropin, free thyroxine, thyroid peroxidase antibodies) were measured at a mean (SD) of 13.6 (1.9) weeks of gestation. Children's ADHD symptoms were assessed at 8 years of age using the Conners' Parent Rating Scale Revised Short Form; higher scores indicate more ADHD symptoms (possible range, 0 36). RESULTS: Maternal hypothyroxinemia (n = 127) in early pregnancy was associated with higher scores for ADHD symptoms in children at 8 years of age after adjustments for child and maternal factors (ie, sex, ethnicity, maternal age, maternal educational level, and income) (increase in ADHD scores, 7% [95% CI, 0.3%-15%]). The results remained essentially unchanged when women with elevated levels of thyroid peroxidase antibodies were excluded from the analyses (increase in ADHD scores, 8% [95% CI, 1%-16%]). Additional adjustment for children's IQ or comorbid autistic symptoms attenuated the association (increase in ADHD scores adjusted for autistic symptoms, 7% [95% CI, 1%-15%]; increase in ADHD scores adjusted for IQ, 6% [95% CI, 1%-14%]). CONCLUSIONS AND RELEVANCE: Children exposed to maternal hypothyroxinemia in early pregnancy had more ADHD symptoms, independent of confounders. This finding suggests that intrauterine exposure to insufficient thyroid hormone levels influences neurodevelopment in offspring. PMID- 26146877 TI - Validation of a method to measure light distortion surrounding a source of glare. AB - Our objective was to validate a new device dedicated to measure the light disturbances surrounding bright sources of light under different sources of potential variability. Twenty subjects were involved in the study. Light distortion was measured using an experimental prototype (light distortion analyzer, CEORLab, University of Minho, Portugal) comprising twenty-four LED arrays panel at 2 m. Sources of variability included: intrasession and intersession repeated measures, pupil size (3 versus 6 mm), defocus (+0.50 ) correction for the working distance, angular resolution (15 deg versus 30 deg), temporal stimuli presentation, and pupil size. Size, shape, location, and irregularity parameters have been obtained. At a low speed of presentation of the stimuli, changes in angular resolution did not have an effect on the results of the parameters measured. Results did not change with pupil size. Intensity of the central glare source significantly influenced the outcomes. Examination time was reduced by 30% when a 30 deg angular resolution was explored instead of 15 deg. Measurements were fast and repeatable under the same experimental conditions. Size and shape parameters showed the highest consistency, whereas location and irregularity parameters showed lower consistency. The system was sensitive to changes in the intensity of the central glare source but not to pupil changes in this sample of healthy subjects PMID- 26146874 TI - Addiction pharmacogenetics: a systematic review of the genetic variation of the dopaminergic system. AB - Substance use disorders have significant personal, familial, and societal consequences. Despite the serious consequences of substance use, only a few therapies are effective in treating substance use disorders, thus highlighting a need for improved treatment practices. Substance use treatment response depends on multiple factors such as genetic, biological, and social factors. It is essential that each component is represented in treatment plans. The dopaminergic system plays a critical role in the pharmacotherapy for addictions, and an understanding of the role of variation of genes involved in this system is essential for its success. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement guidelines. A computerized literature search was conducted using PubMed and Scopus (all databases). Articles published up to April 2015 that examined the role of dopaminergic gene variation in the pharmacotherapy of alcohol, opioid, and cocaine use disorders were reviewed. Search terms were dopamine, gene, polymorphism, substance abuse, treatment, and response. Polymorphisms of the DRD2, ANKK1, DAT1, DBH, and DRD4 genes have been found to moderate the effects of pharmacotherapy of alcohol, opioid, and cocaine use disorders. The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders. More studies are needed to confirm and extend these findings. PMID- 26146878 TI - Three-dimensional imaging and uptake of the anticancer drug combretastatin in cell spheroids and photoisomerization in gels with multiphoton excitation. AB - The uptake of E -combretastatins, potential prodrugs of the anticancer Z isomers, into multicellular spheroids has been imaged by intrinsic fluorescence in three dimensions using two-photon excited fluorescence lifetime imaging with 625-nm ultrafast femtosecond laser pulses. Uptake is initially observed at the spheroid periphery but extends to the spheroid core within 30 min. Using agarose gels as a three-dimensional model, the conversion of Z(trans)->E(cis) via two photon photoisomerization is demonstrated and the location of this photochemical process may be precisely selected within the micron scale in all three dimensions at depths up to almost 2 mm. We discuss these results for enhanced tissue penetration at longer near-infrared wavelengths for cancer therapy and up to three-photon excitation and imaging using 930-nm laser pulses with suitable combretastatin analogs. PMID- 26146879 TI - The post modern p=1.0. PMID- 26146880 TI - Toward Efficient Nucleophilic Azaborine Building Blocks for the Synthesis of B-N Naphthyl (Hetero)arylmethane Isosteres. AB - To develop a method for the synthesis of a class of azaborines, potassium 2 (trifluoroboratomethyl)-2,1-borazaronaphthalenes have been synthesized to serve as nucleophilic building blocks. In palladium-catalyzed cross-coupling reactions with (hetero)aryl chlorides they serve to produce a variety of pseudobenzylic (hetero)aryl substituted azaborines. Potassium 2-(trifluoroboratomethyl)-2,1 borazaronaphthalenes are crystalline solids that are more stable than 2 (chloromethyl)-2,1-borazaronaphthalenes and have a broader substrate scope in cross-coupling reactions compared to their pseudobenzylic chloride counterparts. PMID- 26146881 TI - Selection for a Single Self-Assembled Macrocycle from a Hybrid Metal-Ligand Hydrogen-Bonded (MLHB) Ligand Subunit. AB - To expand the interface between self-assembled metal-ligand and hydrogen-bonded architectures, here we report the preparation, self-assembly, and metal-ligand binding of a pyridyl quinolone ligand (5-PYQ). The 5-PYQ ligand self-associates through quinolone hydrogen bonding, and it binds to metal centers through the pyridine ligand component. As a first step toward investigating more-complex hybrid metal-ligand hydrogen-bonded (MLHB) architectures, we report investigations of 5-PYQ with mono- and bis-platinated anthracene precursors. These results demonstrate that the 5-PYQ ligand maintains hydrogen bonding interactions while binding to square-planar platinum centers, but that generation of coordination compounds with closed topology erodes the hydrogen bonding fidelity to favor ambidentate coordination modes of the 5-PYQ ligand. PMID- 26146882 TI - Imaging Endogenous Bilirubins with Two-Photon Fluorescence of Bilirubin Dimers. AB - On the basis of an infrared femtosecond Cr:forsterite laser, we developed a semiquantitative method to analyze the microscopic distribution of bilirubins. Using 1230 nm femtosecond pulses, we selectively excited the two-photon red fluorescence of bilirubin dimers around 660 nm. Autofluorescences from other endogenous fluorophores were greatly suppressed. Using this distinct fluorescence measure, we found that poorly differentiated hepatocellular carcinoma (HCC) tissues on average showed 3.7 times lower concentration of bilirubins than the corresponding nontumor parts. The corresponding fluorescence lifetime measurements indicated that HCC tissues exhibited a longer lifetime (500 ps) than that of nontumor parts (300 ps). Similarly, oral cancer cell lines had longer lifetimes (>330 ps) than those of nontumor ones (250 ps). We anticipate the developed methods of bilirubin molecular imaging to be useful in diagnosing cancers or studying the dynamics of bilirubin metabolisms in live cells. PMID- 26146883 TI - Highly Sensitive Detection and Removal of Lead Ions in Water Using Cysteine Functionalized Graphene Oxide/Polypyrrole Nanocomposite Film Electrode. AB - We synthesized cysteine-functionalized graphene oxide (sGO) using carbonyldiimidazole as a cross-linker via amide and carbamate linkages. The sGO/polypyrrole (PPy) nanocomposite film was grown on the working electrode surface of a screen-printed electrode (SPE) via controlled one-step electrochemical deposition. The sGO/PPy-SPE was used to detect lead ions (Pb(2+)) in water by first depositing Pb(2+) on the working electrode surface for 10 min at -1.2 V, and then anodic stripping by differential pulse voltammetry (DPV). The DPV signals were linear in the ranges of 1.4-28 ppb (R(2) = 0.994), 28-280 ppb (R(2) = 0.997), and 280-14 000 ppb (R(2) = 0.990) Pb(2+). The measurable detection limit of the sensor is 0.07 ppb (S/N = 3), which is more than 2 orders of magnitude below the 10 ppb threshold for drinking water set by the World Health Organization. The average removal efficiency of Pb(2+) deposited on the electrode was 99.2% (S/N = 3), with relative standard deviation (RSD) of 3.8%. Our results indicate good affinity of sGO/PPy nanocomposite to Pb(2+), which can be used to effectively adsorb and remove Pb(2+) in water samples. Therefore, sGO/PPy nanocomposite we synthesized is useful for highly sensitive on-site and real-time monitoring of heavy metal ions and water treatment. PMID- 26146884 TI - Experimental Evidence for Proposed Transformation Pathway from the Inverse Hexagonal to Inverse Diamond Cubic Phase from Oriented Lipid Samples. AB - A macroscopically oriented inverse hexagonal phase (HII) of the lipid phytantriol in water is converted to an oriented inverse double diamond bicontinuous cubic phase (QII(D)). The initial HII phase is uniaxially oriented about the long axis of a capillary with the cylinders parallel to the capillary axis. The HII phase is converted by cooling to a QII(D) phase which is also highly oriented, where the cylindrical axis of the former phase has been converted to a ?110? axis in the latter, as demonstrated by small-angle X-ray scattering. This epitaxial relationship allows us to discriminate between two competing proposed geometric pathways to convert HII to QII(D). Our findings also suggest a new route to highly oriented cubic phase coatings, with applications as nanomaterial templates. PMID- 26146885 TI - Openness as a buffer against cognitive decline: The Openness-Fluid-Crystallized Intelligence (OFCI) model applied to late adulthood. AB - Explaining cognitive decline in late adulthood is a major research area. Models using personality traits as possible influential variables are rare. This study tested assumptions based on an adapted version of the Openness-Fluid-Crystallized Intelligence (OFCI) model. The OFCI model adapted to late adulthood predicts that openness is related to the decline in fluid reasoning (Gf) through environmental enrichment. Gf should be related to the development of comprehension knowledge (Gc; investment theory). It was also assumed that Gf predicts changes in openness as suggested by the environmental success hypothesis. Finally, the OFCI model proposes that openness has an indirect influence on the decline in Gc through its effect on Gf (mediation hypothesis). Using data from the Berlin Aging Study (N = 516, 70-103 years at T1), these predictions were tested using latent change score and latent growth curve models with indicators of each trait. The current findings and prior research support environmental enrichment and success, investment theory, and partially the mediation hypotheses. Based on a summary of all findings, the OFCI model for late adulthood is suggested. PMID- 26146886 TI - Responses to patronizing communication and factors that attenuate those responses. AB - The purpose of this study was to investigate younger (n = 52, ages 18-24) and older (n = 69, ages 61-98) adults' responses to patronizing communication in terms of (a) performance on a cognitive task (Weschler Adult Intelligence Scale III block design) and (b) physiological responses (i.e., change in cortisol levels), as well as factors that may attenuate those responses. Participants were randomly assigned to receive instructions for the task using either a patronizing or nonpatronizing speech style. Participants also completed a measure of attitudes about aging and the quantity/quality of their intergenerational interaction. Older adults (relative to younger adults) were found to be more reactive to the patronizing speech style in terms of their performance on the task as well as the change in their cortisol levels. Older adults who had more positive attitudes about aging as well as more positive intergenerational interactions were protected from the performance deficits as a result of patronizing speech style. These findings could be used to inform social programs aimed at reducing age-based stigma and improving the life course outcomes of our aging population. PMID- 26146887 TI - Understanding inter-individual variability in purpose: Longitudinal findings from the VA Normative Aging Study. AB - Research has demonstrated the importance of having a purpose in older adulthood; however, little is known about whether and how individuals vary on sense of purpose over time. The current study examined patterns of mean- and individual level change in purpose among men in the Veterans Affairs Normative Aging Study (n = 587, M(age) = 74 years) across a 3-year span. Findings demonstrate that while little mean-level change was present, there was interindividual variability in change. Further research is needed to understand why these changes occur, as age, health status, and personality failed to predict individual fluctuations in purpose. PMID- 26146888 TI - Insights into the Lactonase Mechanism of Serum Paraoxonase 1 (PON1): Experimental and Quantum Mechanics/Molecular Mechanics (QM/MM) Studies. AB - Serum paraoxonase 1 (PON1) is a versatile enzyme for the hydrolysis of various substrates (e.g., lactones, phosphotriesters) and for the formation of a promising chemical platform gamma-valerolactone. Elucidation of the PON1 catalyzed lactonase reaction mechanism is very important for understanding the enzyme function and for engineering this enzyme for specific applications. Kinetic study and hybrid quantum mechanics/molecular mechanics (QM/MM) method were used to investigate the PON1-catalyzed lactonase reaction of gamma butyrolactone (GBL) and (R)-gamma-valerolactone (GVL). The activation energies obtained from the QM/MM calculations were in good agreement with the experiments. Interestingly, the QM/MM energy barriers at MP2/3-21G(d,p) level for the lactonase of GVL and GBL were respectively 14.3-16.2 and 11.5-13.1 kcal/mol, consistent with the experimental values (15.57 and 14.73 kcal/mol derived from respective kcat values of 36.62 and 147.21 s(-1)). The QM/MM energy barriers at MP2/6-31G(d) and MP2/6-31G(d,p) levels were also in relatively good agreements with the experiments. Importantly, the difference in the QM/MM energy barriers at MP2 level with all investigated basis sets for the lactonase of GVL and GBL were in excellent agreement with the experiments (0.9-3.1 and 0.8 kcal/mol, respectively). A detailed mechanism for the PON1-catalyzed lactonase reaction was also proposed in this study. PMID- 26146889 TI - A new approach for treatment of precancerous lesions with curcumin solid-lipid nanoparticle-loaded gels: in vitro and clinical evaluation. AB - OBJECTIVE: Preparation and characterization of curcumin solid-lipid nanoparticle (CurSLN)-loaded mucoadhesive gel for local treatment of oral precancerous lesions with low dose. METHODOLOGY: The formulated CurSLNs were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. Conventional mucoadhesive gel using binary system was adopted. The prepared gels were evaluated for in vitro drug dialysis, ex vivo mucoadhesion test and ex vivo permeation study using chicken buccal mucosa. Short-term clinical evaluation was carried out on 10 patients suffering oral erythroplakia in terms of pain index and lesion size measurement. (1) RESULTS: The results showed that the loaded gel with CurSLN showed good mucoadhesion property and 25 min in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated, however, significant amount of Cur was retained within the chicken buccal mucosal tissue confirmed by histological examination. Significant reduction in pain, and complete healing was observed after 6 weeks of treatment. CONCLUSION: The local use of Cur in low dose is a promising option for treatment of precancerous lesions. The lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose. PMID- 26146890 TI - Preliminary study on implantable inductive-type sensor for continuous monitoring of intraocular pressure. AB - BACKGROUND: This study aims to validate the performance and biocompatibility of an implantable inductive-type sensor for continuous monitoring of intraocular pressure (IOP) METHODS: The sensor is composed of a top layer integrated with an inductor and capacitor circuit, and a bottom layer integrated with ferrite. With IOP change, the sensor's bottom layer is mechanically deflected, which changes the distance between the bottom-layer ferrite and top-layer inductor, resulting in an alteration of inductance magnitude and the resonant frequency (RF). In vitro measurement was conducted via air pressurization in a sealing jig (n = 3). Subsequently, the sensor was implanted into the anterior chamber of a rabbit eye. In-vivo measurement was performed while the IOP was elevated by infusion of balanced salt solution (BSS, 6 MUL/min). Smaller-sized sensors later were implanted into two rabbit eyes, which were microscopically examined at 2, 4 and 8 weeks post-implantation. The eyes were then immediately enucleated for histological examination. RESULTS: The in-vitro measurement showed a significant RF shift as pressure in the jig was increased from 0 mmHg to 60 mmHg (average initial frequency: 10.86 MHz, average shift: 403 kHz). The in-vivo measurement also showed an RF decrease, from 12.80 MHz to 12.67 MHz, as the pressure was increased from 10 mmHg to 20 mmHg. Microscopic in-vivo evaluations and histological exams, performed at intervals up to 8 weeks post-implantation, showed no evidence of significant inflammation or deformity of the ocular-tissue structures. CONCLUSIONS: The implantable inductive-type IOP sensor demonstrated wireless pressure-sensing ability and favourable biocompatibility in the rabbit eye. PMID- 26146891 TI - An integrated ceramic, micro-fluidic device for the LC/MS/MS analysis of pharmaceuticals in plasma. AB - An integrated capillary scale (300 MUm id) ceramic microfluidic LC system combined with MS/MS has been successfully employed for the quantitative analysis of pharmaceutical compounds in human plasma. The capillary ceramic microfluidic LC/MS/MS system showed an approximate 20-fold (range 11-38-fold) increase in sensitivity compared with a standard 2.1 mm scale UPLC/MS/MS system for a broad range of analytes. The loading capacity of the devices capillary separations channel allowed injection of 2 MUL of an aqueous solution, and up to 1.2 MUL of a typical protein-precipitated plasma sample, onto the reversed-phase chromatography system. The system also showed excellent chromatographic performance and robustness, with no deleterious effects on the chromatography observed over the course of 1000 injections of protein-precipitated plasma. The ability of the ceramic microfluidic LC/MS/MS system to deliver this level of sensitivity and performance enables the routine quantification of pharmaceutical compounds from small format samples, such as those obtained by dried blood spot or other blood microsampling approaches, to be performed. PMID- 26146892 TI - Considerations for the Conduct of Clinical Trials with Antiinflammatory Agents in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report. AB - Inflammation leads to lung destruction and loss of pulmonary function in patients with cystic fibrosis (CF). Drugs that modulate the cystic fibrosis transmembrane conductance regulator (CFTR) have recently been approved. Although the impact of CFTR modulators on sweat chloride and lung function are exciting, they have not yet demonstrated an effect on inflammation. Therefore, CF antiinflammatory drug development must continue. Unfortunately, the lack of clarity with this process has left investigators and industry sponsors frustrated. The Cystic Fibrosis Foundation established a working group in early 2014 to address this issue. There are many inflammatory processes disrupted in CF, and, therefore, there are many potential targets amenable to antiinflammatory therapy. Regardless of a drug's specific mechanism of action, it must ultimately affect the neutrophil or its products to impact CF. The working group concluded that before bringing new antiinflammatory drugs to clinical trial, preclinical safety studies must be conducted in disease-relevant models to assuage safety concerns. Furthermore, although studies of antiinflammatory therapies must first establish safety in adults, subsequent studies must involve children, as they are most likely to reap the most benefit. The working group also recommended that pharmacokinetic pharmacodynamic studies and early-phase safety studies be performed before proceeding to larger studies of longer duration. In addition, innovative study designs may improve the likelihood of adequately assessing treatment response and mitigating risk before conducting multiyear studies. Learning from past experiences and incorporating this knowledge into new drug development programs will be instrumental in bringing new antiinflammatory therapies to patients. PMID- 26146893 TI - The Effect of Atorvastatin on Cardiometabolic Risk Factors in Bromocriptine Treated Premenopausal Women with Isolated Hypercholesterolemia. AB - AIMS: Hyperprolactinemia is often associated with hyperinsulinemia, insulin resistance, atherogenic dyslipidemia, and subclinical atherosclerosis. Dopamine agonists were found to reduce the prevalence of metabolic syndrome and cardiometabolic risk. The aim of this study was to compare the effect of statin therapy on cardiovascular risk factors between patients treated with a dopamine agonist and patients treated with metformin. METHODS: The study included two age , weight-, lipid-, and prolactin level-matched groups of premenopausal women with hypecholesterolemia and a history of hyperprolactinemia: patients treated with bromocriptine (5.0-7.5 mg daily, n = 14) and subjects receiving metformin (1.7 2.55 g daily, n = 17). Plasma prolactin, lipids, glucose homeostasis markers, and plasma levels of cardiometabolic risk factors were assessed before and after 12 weeks of atorvastatin treatment. RESULTS: Baseline levels of the investigated variables were similar in women treated with bromocriptine and metformin. Apart from lowering total and LDL cholesterol, atorvastatin decreased plasma levels of uric acid, hsCRP, homocysteine, and fibrinogen, with no difference between treatment groups. CONCLUSIONS: The obtained results suggest that the effect of atorvastatin on plasma lipids and circulating levels of cardiometabolic risk factors does not differ between patients receiving bromocriptine and metformin. Bromocriptine-statin combination therapy may be an alternative to metformin statin combination therapy in hypercholesterolemic patients with glucose metabolism abnormalities in whom metformin administration is either contraindicated or results in adverse effects. PMID- 26146894 TI - Age-specific neuromuscular interaction during elderly habitual running. AB - AIM: It has been reported that advancing age causes tendons to become more compliant and fascicles length shorter. This could then lead to enhancement of movement efficiency provided that the elderly adults can activate their muscles in the same way as the younger adults (YOUNG) during dynamic movements. This study was designed to examine the age-specific behaviour of the medial gastrocnemius (MG) fascicles and tendinous tissues together with lower-leg muscle activities when the well-trained elderly runners ran on the treadmill at preferred speeds. METHODS: The well-trained 11 elderly subjects (ELD) who have running experiences and 11 YOUNG were recruited as subjects. While ELD were running on the treadmill at their preferred speed, the lengths of the MG fascicles and tendinous tissues (Lfa and LTT respectively) were measured by ultrasonography together with kinematics and lower-leg muscle activities. RESULTS: Although the behaviour of the MG muscle-tendon unit did not show any significant differences between both groups during the contact, our results showed significant differences in fascicle-tendinous tissue behaviour as well as muscle activities. The LTT during the entire contact phase was greater in ELD than in YOUNG (P < 0.001). Co-activation of lower-leg muscles from pre-activation to braking phases was higher in ELD than in YOUNG (P < 0.01). The changes of the Lfa during contact were less, and the LTT shortening was greater in ELD than in YOUNG (P < 0.001). CONCLUSION: These results imply that ELD cannot activate their muscles similar to YOUNG during running, and those different activities may modify the Lfa to utilize the tendon elasticity effectively. PMID- 26146895 TI - Incidence, Progression, and Associated Risk Factors of Posterior Vitreous Detachment in Type 2 Diabetes Mellitus: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS II, Report No. 7). AB - PURPOSE: To report the incidence and progression of posterior vitreous detachment (PVD) and factors influencing the same in a cohort of patients with type 2 diabetes in a South Indian population. METHODS: A subset of 615 subjects from Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study II were included in this study. All of the subjects underwent detailed ophthalmic evaluation including stereo fundus photography. The status of PVD was assessed using B-scan ultrasonography. A p value of <0.05 was considered statistically significant. RESULTS: The incidence of either incomplete PVD (IPVD) or complete PVD (CPVD) from no PVD at baseline visit was 80.8%. Of them, 32.63% converted to CPVD from IPVD at baseline. High prevalence of emmetropia was observed in subjects with stable No PVD. Risk factors associated with the conversion of CPVD from no PVD and IPVD at baseline were age (OR: 1.04, p = 0.002), myopia (OR: 2.14, p = 0.009), and increase in axial length (OR: 1.35, p = 0.004). Subjects undergoing cataract surgery were at 2.32 times higher risk of converting to CPVD (p = 0.038). CONCLUSION: Independent risk factors for the progression of PVD were increase in age, myopia, increased axial length, and cataract surgery. PMID- 26146896 TI - Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1. AB - AIMS AND BACKGROUND: Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians. MATERIAL AND METHODS: Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi square test with a significance threshold of P < 0.05 (compare 2, version 1.02). RESULTS: The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P = 0.0027, RR = 18.27 (20.0061-915.28)). CONCLUSION: Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis. PMID- 26146900 TI - Diagnosing options in patient with sarcopenia. PMID- 26146897 TI - A new insight into root responses to external cues: Paradigm shift in nutrient sensing. AB - Higher plants are sessile and their growth relies on nutrients present in the soil. The acquisition of nutrients is challenging for plants. Phosphate and nitrate sensing and signaling cascades play significant role during adverse conditions of nutrient unavailability. Therefore, it is important to dissect the mechanism by which plant roots acquire nutrients from the soil. Root system architecture (RSA) exhibits extensive developmental flexibility and changes during nutrient stress conditions. Growth of root system in response to external concentration of nutrients is a joint operation of sensor or receptor proteins along with several other cytoplasmic accessory proteins. After nutrient sensing, sensor proteins start the cellular relay involving transcription factors, kinases, ubiquitin ligases and miRNA. The complexity of nutrient sensing is still nebulous and many new players need to be better studied. This review presents a survey of recent paradigm shift in the advancements in nutrient sensing in relation to plant roots. PMID- 26146901 TI - Increased noradrenergic neurotransmission to a pain facilitatory area of the brain is implicated in facilitation of chronic pain. AB - BACKGROUND: Noradrenaline reuptake inhibitors are known to produce analgesia through a spinal action but they also act in the brain. However, the action of noradrenaline on supraspinal pain control regions is understudied. The authors addressed the noradrenergic modulation of the dorsal reticular nucleus (DRt), a medullary pronociceptive area, in the spared nerve injury (SNI) model of neuropathic pain. METHODS: The expression of the phosphorylated cAMP response element-binding protein (pCREB), a marker of neuronal activation, was evaluated in the locus coeruleus and A5 noradrenergic neurons (n = 6 rats/group). pCREB was studied in noradrenergic DRt-projecting neurons retrogradely labeled in SNI animals (n = 3). In vivo microdialysis was used to measure noradrenaline release in the DRt on nociceptive stimulation or after DRt infusion of clonidine (n = 5 to 6 per group). Pharmacology, immunohistochemistry, and western blot were used to study alpha-adrenoreceptors in the DRt (n = 4 to 6 per group). RESULTS: pCREB expression significantly increased in the locus coeruleus and A5 of SNI animals, and most noradrenergic DRt-projecting neurons expressed pCREB. In SNI animals, noradrenaline levels significantly increased on pinprick (mean +/- SD, 126 +/- 14%; P = 0.025 vs. baseline) and acetone stimulation (mean +/- SD, 151 +/- 12%; P < 0.001 vs. baseline), and clonidine infusion showed decreased alpha2-mediated inhibitory function. alpha1-adrenoreceptor blockade decreased nociceptive behavioral responses in SNI animals. alpha2-adrenoreceptor expression was not altered. CONCLUSIONS: Chronic pain induces brainstem noradrenergic activation that enhances descending facilitation from the DRt. This suggests that antidepressants inhibiting noradrenaline reuptake may enhance pain facilitation from the brain, counteracting their analgesic effects at the spinal cord. PMID- 26146898 TI - Combined Whole Methylome and Genomewide Association Study Implicates CNTN4 in Alcohol Use. AB - BACKGROUND: Methylome-wide association (MWAS) studies present a new way to advance the search for biological correlates for alcohol use. A challenge with methylation studies of alcohol involves the causal direction of significant methylation-alcohol associations. One way to address this issue is to combine MWAS data with genomewide association study (GWAS) data. METHODS: Here, we combined MWAS and GWAS results for alcohol use from 619 individuals. Our MWAS data were generated by next-generation sequencing of the methylated genomic DNA fraction, producing over 60 million reads per subject to interrogate methylation levels at ~27 million autosomal CpG sites in the human genome. Our GWAS included 5,571,786 single nucleotide polymorphisms (SNPs) imputed with 1000 Genomes. RESULTS: When combining the MWAS and GWAS data, our top finding was a region in an intron of CNTN4 (p = 2.55 * 10(-8) ), located between chr3: 2,555,403 and 2,555,524, encompassing SNPs rs1382874 and rs1382875. This finding was then replicated in an independent sample of 730 individuals. We used bisulfite pyrosequencing to measure methylation and found significant association with regular alcohol use in the same direction as the MWAS (p = 0.021). Rs1382874 and rs1382875 were genotyped and found to be associated in the same direction as the GWAS (p = 0.008 and p = 0.009). After integrating the MWAS and GWAS findings from the replication sample, we replicated our combined analysis finding (p = 0.0017) in CNTN4. CONCLUSIONS: Through combining methylation and SNP data, we have identified CNTN4 as a risk factor for regular alcohol use. PMID- 26146902 TI - 'Volumetric analysis of hand and rotary root canal instrumentation and filling in primary teeth using Spiral Computed Tomography' - an invitro study. AB - AIM: To compare and evaluate the volumetric analysis of pre- and post-root canal instrumentation in primary teeth using hand and rotary files and also to analyse the volume of root canal filling. MATERIALS AND METHODS: A total of 20 primary teeth were divided into two groups randomly and subjected to spiral computed tomography (SCT) analysis before and after instrumentation. For manual technique (Group 1), teeth were prepared using K files and rotary (Group 2) preparation was performed with Mtwo files. Volumetric enlargement was calculated using Osirix software. Root canals were then filled with rotary lentulospiral using zinc oxide eugenol cement (ZOE). The filled volume in each canal was measured using SCT and the percentage of obturated volume was calculated. The data were statistically analysed using paired t-tests. RESULTS: There was a statistically significant difference in the volume of root canal enlarged in both the groups. Rotary files showed significant increase in the volume compared to K files. Mtwo instrumented root canals showed good obturated volume compared to manual technique, although voids were common in both the groups. CONCLUSION: Rotary root canal instrumentation may be indicated for utilization in primary teeth, for enhancing root canal preparation and good quality of root canal filling. PMID- 26146905 TI - Health prevention in the era of biosocieties: a critical analysis of the 'Seek and-Treat' paradigm in HIV/AIDS prevention. AB - On 18 November 2014, the United Nations launched an urgent new campaign to end AIDS as a global health threat by 2030. With its proposed strategy, the UN follows leading scientists who had declared the failure of former prevention strategies and now were promoting a 'Seek and Treat for Optimal Prevention' (STOP) approach as the most cost-effective response to the pandemic to meet the goal of 'an AIDS-free generation'. STOP combines antiretroviral therapy and routine HIV screening to find persons unaware that they are HIV-positive, because research has shown that people consistently change their behaviour (i.e. increase condom use, have fewer partners) after an HIV diagnosis. AIDS activists have broadly criticized this strategy on different levels. In this article, we go beyond these criticisms and try to analyse the political rationalities behind this 'new' strategy. We believe that it is necessary to put the rationale underpinning the STOP programme into the context of broader societal transformations that can best be captured as the development of advanced liberal societies and the new emphasis on self-controlling or self-responsibility rather than on disciplining behaviour. PMID- 26146907 TI - The Effect of Burn Center Volume on Mortality in a Pediatric Population: An Analysis of the National Burn Repository. AB - The effect of burn center volume on mortality has been demonstrated in adults. The authors sought to evaluate whether such a relationship existed in burned children. The National Burn Repository, a voluntary registry sponsored by the American Burn Association, was queried for all data points on patients aged 18 years or less and treated from 2002 to 2011. Facilities were divided into quartiles based on average annual burn volume. Demographics and clinical characteristics were compared across groups, and univariate and multivariate logistic regressions were performed to evaluate relationships between facility volume, patient characteristics, and mortality. The authors analyzed 38,234 patients admitted to 88 unique facilities. Children under age 4 years or with larger burns were more likely to be managed at high-volume and very high-volume centers (57.12 and 53.41%, respectively). Overall mortality was low (0.85%). Comparing mortality across quartiles demonstrated improved unadjusted mortality rates at the low- and high-volume centers compared with the medium-volume and very high-volume centers although univariate logistic regression did not find a significant relationship. However, multivariate analysis identified burn center volume as a significant predictor of decreased mortality after controlling for patient characteristics including age, mechanism of injury, burn size, and presence of inhalation injury. Mortality among pediatric burn patients is low and was primarily related to patient and injury characteristics, such as burn size, inhalation injury, and burn cause. Average annual admission rate had a significant but small effect on mortality when injury characteristics were considered. PMID- 26146908 TI - Reasons Why Physicians and Advanced Practice Clinicians Work While Sick: A Mixed Methods Analysis. AB - IMPORTANCE: When clinicians work with symptoms of infection, they can put patients and colleagues at risk. Little is known about the reasons why attending physicians and advanced practice clinicians (APCs) work while sick. OBJECTIVE: To identify a comprehensive understanding of the reasons why attending physicians and APCs work while sick. DESIGN, SETTING, AND PARTICIPANTS: We performed a mixed methods analysis of a cross-sectional, anonymous survey administered from January 15 through March 20, 2014, in a large children's hospital in Philadelphia, Pennsylvania. Data were analyzed from April 1 through June 1, 2014. The survey was administered to 459 attending physicians and 470 APCs, including certified registered nurse practitioners, physician assistants, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives. MAIN OUTCOMES AND MEASURES: Self-reported frequency of working while experiencing symptoms of infection, perceived importance of various factors that encourage working while sick, and free-text comments written in response to open-ended questions. RESULTS: Of those surveyed, we received responses from 280 attending physicians (61.0%) and 256 APCs (54.5%). Most of the respondents (504 [95.3%]) believed that working while sick put patients at risk. Despite this belief, 446 respondents (83.1%) reported working sick at least 1 time in the past year, and 50 (9.3%) reported working while sick at least 5 times. Respondents would work with significant symptoms, including diarrhea (161 [30.0%]), fever (86 [16.0%]), and acute onset of significant respiratory symptoms (299 [55.6%]). Physicians were more likely to report working with each of these symptoms than APCs (109 [38.9%] vs 51 [19.9%], 61 [21.8%] vs 25 [9.8%], and 168 [60.0%] vs 130 [50.8%], respectively [P < .05]). Reasons deemed important in deciding to work while sick included not wanting to let colleagues down (521 [98.7%]), staffing concerns (505 [94.9%]), not wanting to let patients down (494 [92.5%]), fear of ostracism by colleagues (342 [64.0%]), and concern about continuity of care (337 [63.8%]). Systematic qualitative analysis of free-text comments from 316 respondents revealed additional reasons why attending physicians and APCs work while sick, including extreme difficulty finding coverage (205 [64.9%]), a strong cultural norm to come to work unless remarkably ill (193 [61.1%]), and ambiguity about what constitutes "too sick to work" (180 [57.0%]). CONCLUSIONS AND RELEVANCE: Attending physicians and APCs frequently work while sick despite recognizing that this choice puts patients at risk. The decision to work sick is shaped by systems level and sociocultural factors. Multimodal interventions are needed to reduce the frequency of this behavior. PMID- 26146906 TI - Deficits in behavioral sensitization and dopaminergic responses to methamphetamine in adenylyl cyclase 1/8-deficient mice. AB - The cAMP/protein kinase A pathway regulates methamphetamine (METH)-induced neuroplasticity underlying behavioral sensitization. We hypothesize that adenylyl cyclases (AC) 1/8 mediate these neuroplastic events and associated striatal dopamine regulation. Locomotor responses to METH (1 and 5 mg/kg) and striatal dopamine function were evaluated in mice lacking AC 1/8 (DKO) and wild-type (WT) mice. Only 5 mg/kg METH induced an acute locomotor response in DKO mice, which was significantly attenuated versus WT controls. DKO mice showed a marked attenuation in the development and expression of METH-induced behavioral sensitization across doses relative to WT controls. While basal and acute METH (5 mg/kg)-evoked accumbal dialysate dopamine levels were similar between genotypes, saline-treated DKO mice showed elevated tissue content of dopamine and homovanillic acid in the dorsal striatum (DS), reflecting dysregulated dopamine homeostasis and/or metabolism. Significant reductions in DS dopamine levels were observed in METH-sensitized DKO mice compared to saline-treated controls, an effect not observed in WT mice. Notably, saline-treated DKO mice had significantly increased phosphorylated Dopamine- and cAMP-regulated phosphoprotein levels, which were not further augmented following METH sensitization, as observed in WT mice. These data indicate that AC 1/8 are critical to mechanisms subserving drug-induced behavioral sensitization and mediate nigrostriatal pathway METH sensitivity. Calcium/calmodulin-stimulated adenylyl cyclase (AC) isoforms 1 and 8 were studied for their involvement in the adaptive neurobehavioral responses to methamphetamine. AC 1/8 double knockout (DKO) mice showed heightened basal locomotor activity and dorsal striatal dopamine responsivity. Conversely, methamphetamine-induced locomotor activity was attenuated in DKO mice, accompanied by reductions in dopamine and HVA content and impaired DARPP-32 activation. These findings indicate AC 1/8 signaling regulates the sensitivity of the nigrostriatal pathway subserving stimulant and neuroadaptive sensitizing effects of methamphetamine. 3-MT, 3-methoxytyramine; Ca(2+), calcium; CaM, calmodulin; cdk5; cyclin-dependent kinase 5; DA, dopamine; DARPP-32, dopamine- and cAMP-regulated phosphoprotein; D1R, dopamine D1 receptor; HVA, homovanillic acid; PKA, protein kinase A. PMID- 26146909 TI - Lip Lesions: Lichen Planus vs. Solar Cheilitis. PMID- 26146912 TI - Hyperbaric Oxygen Treatment for Persistent Postconcussion Symptoms--A Placebo Effect? PMID- 26146913 TI - Hyperbaric Oxygen Treatment for Persistent Postconcussion Symptoms--Reply. PMID- 26146914 TI - Carotid Endarterectomy for Asymptomatic Stenosis. PMID- 26146915 TI - Hyperbaric Oxygen Treatment for Persistent Postconcussion Symptoms--Reply. PMID- 26146916 TI - One-Year Risk of Bleeding With Dabigatran in Patients With Atrial Fibrillation: Placing Real-World Results Into Perspective. PMID- 26146917 TI - Bleeding in Patients of African Ancestry Using Dabigatran: A Potential Effect of Creatine Kinase. PMID- 26146918 TI - The Role of Selection in the Risk of Bleeding With Dabigatran in Patients With Atrial Fibrillation. PMID- 26146919 TI - A Methodological Appraisal of Recent Real-World Data Publications on Dabigatran. PMID- 26146920 TI - Dosage of Dabigatran as a Risk Factor for Bleeding in Atrial Fibrillation. PMID- 26146921 TI - Patient Characteristics and Risk of Bleeding With Dabigatran in Atrial Fibrillation. PMID- 26146922 TI - Risk of Bleeding With Dabigatran in 2010-2011 Medicare Data. PMID- 26146923 TI - Error in Text and Table. Influence of Institutional Culture and Policies on Do Not-Resuscitate Decision Making at the End of Life. PMID- 26146924 TI - Error in Byline. A Targeted Infection Prevention Intervention in Nursing Home Residents With Indwelling Devices: A Randomized Clinical Trial. PMID- 26146925 TI - Error in Table. Development and Validation of the Good Outcome Following Attempted Resuscitation (GO-FAR) Score to Predict Neurologically Intact Survival After In-Hospital Cardiopulmonary Resuscitation. PMID- 26146927 TI - Increased Left Ventricular Trabeculation Does Not Necessarily Equate to Left Ventricular Noncompaction in Athletes. PMID- 26146929 TI - Incorrect Numbers in Abstract. Comparative Safety of Testosterone Dosage Forms. PMID- 26146928 TI - Error in Text. Effect of Moderate to Vigorous Physical Activity on All-Cause Mortality in Middle-aged and Older Australians. PMID- 26146930 TI - Error in Author Affiliation. Withholding and Withdrawal of Life-Sustaining Treatments in Intensive Care Units in Asia. PMID- 26146931 TI - Correlation, necessity, and sufficiency: Common errors in the scientific reasoning of undergraduate students for interpreting experiments. AB - Gaining an understanding of how science works is central to an undergraduate education in biology and biochemistry. The reasoning required to design or interpret experiments that ask specific questions does not come naturally, and is an essential part of the science process skills that must be learned for an understanding of how scientists conduct research. Gaps in these reasoning skills make it difficult for students to become proficient in reading primary scientific literature. In this study, we assessed the ability of students in an upper division biochemistry laboratory class to use the concepts of correlation, necessity, and sufficiency in interpreting experiments presented in a format and context that is similar to what they would encounter when reading a journal article. The students were assessed before and after completion of a laboratory module where necessary vs. sufficient reasoning was used to design and interpret experiments. The assessment identified two types of errors that were commonly committed by students when interpreting experimental data. When presented with an experiment that only establishes a correlation between a potential intermediate and a known effect, students frequently interpreted the intermediate as being sufficient (causative) for the effect. Also, when presented with an experiment that tests only necessity for an intermediate, they frequently made unsupported conclusions about sufficiency, and vice versa. Completion of the laboratory module and instruction in necessary vs. sufficient reasoning showed some promise for addressing these common errors. PMID- 26146932 TI - Novel Pendant Benzene Disulfonic Acid Blended SPPO Membranes for Alkali Recovery: Fabrication and Properties. AB - To reconcile the trade-off between separation performance and availability of desired material for cation exchange membranes (CEMs), we designed and successfully prepared a novel sulfonated aromatic backbone-based cation exchange precursor named sodium 4,4'-(((((3,3'-disulfo-[1,1'-biphenyl]-4,4'-diyl)bis(oxy)) bis(4,1-phenylene))bis(azanediyl))bis(methylene))bis(benzene-1,3-disulfonate) [DSBPB] from 4,4'-bis(4-aminophenoxy)-[1,1'-biphenyl]-3,3'-disulfonic acid [BAPBDS] by a three-step procedure that included sulfonation, Michael condensation followed by reduction. Prepared DSBPB was used to blend with sulfonated poly(2,6-dimethyl-1,4-phenylene oxide) (SPPO) to get CEMs for alkali recovery via diffusion dialysis. Physiochemical properties and electrochemical performance of prepared membranes can be tuned by varying the dosage of DSBPB. All the thermo-mechanical properties like DMA and TGA were investigated along with water uptake (WR), ion exchange capacity (IEC), dimensional stability, etc. The effect of DSBPB was discussed in brief in connection with alkali recovery and ion conducting channels. The SPPO/DSBPB membranes possess both high water uptake as well as ion exchange capacity with high thermo-mechanical stability. At 25 degrees C the dialysis coefficients (UOH) appeared to be in the range of 0.0048 0.00814 m/h, whereas the separation factor (S) ranged from 12.61 to 36.88 when the membranes were tested for base recovery in Na2WO4/NaOH waste solution. Prepared membranes showed much improved DD performances compared to traditional SPPO membrane and possess the potentiality to be a promising candidate for alkali recovery via diffusion dialysis. PMID- 26146934 TI - Organoid cultures boost human liver cell expansion. PMID- 26146933 TI - Childhood maltreatment increases the risk for visceral obesity. AB - OBJECTIVE: The reports regarding the associations between childhood maltreatment (CM) and body fat composition remain heterogeneous in humans although they are indicated in preclinical studies. In addition, the effects of CM subtypes on different types of body fat are unclear. Thus, in this study, the associations between CM and its subtypes with body fat were determined and the potential pathways were explored. METHODS: The participants were assessed for a history of CM by the Childhood Trauma Questionnaire and were divided into the CM group (with CM exposures) and non-CM group (without CM exposures). Body composition was measured by dual-energy X-ray absorptiometry. Salivary and blood samples were provided by the subjects. RESULTS: Compared with the non-CM group, subjects with a history of CM had greater visceral fat mass (1,136 +/- 160 vs. 836 +/- 116 g, P < 0.05) but not total body fat, android fat, body mass index, or waist-to-hip ratio. In addition, subjects with CM had a blunted cortisol awakening response and elevated inflammatory factors. Correlation analysis indicated that CM subtypes had differential effects on visceral adiposity and cortisol awakening response. CONCLUSIONS: It is suggested by our results that CM exposure is linked with increased visceral fat deposition, and the perturbation of the hypothalamic pituitary-adrenal axis activity and activation of the immune system may be two potential pathways through which this relationship is explained. PMID- 26146935 TI - Divergent Synthesis of Imidazoles and Quinazolines via Pd(OAc)2-Catalyzed Annulation of N-Allylamidines. AB - A Pd(OAc)2-catalyzed divergent synthesis of multisubstituted imidazoles and quinazolines from N-allylamidines has been developed. In the presence of oxidant O2 from air and/or a ligand and Pd(OAc)2, imidazoles were obtained. Nonetheless, under microwave (MW) irradiation in a sealed system, quinazolines as major products were produced. PMID- 26146936 TI - Isotopic evidence for the occurrence of biological nitrification and nitrogen deposition processing in forest canopies. AB - This study examines the role of tree canopies in processing atmospheric nitrogen (Ndep ) for four forests in the United Kingdom subjected to different Ndep : Scots pine and beech stands under high Ndep (HN, 13-19 kg N ha(-1) yr(-1) ), compared to Scots pine and beech stands under low Ndep (LN, 9 kg N ha(-1) yr(-1) ). Changes of NO3 -N and NH4 -N concentrations in rainfall (RF) and throughfall (TF) together with a quadruple isotope approach, which combines delta(18) O, Delta(17) O and delta(15) N in NO3 (-) and delta(15) N in NH4 (+) , were used to assess N transformations by the canopies. Generally, HN sites showed higher NH4 N and NO3 -N concentrations in RF compared to the LN sites. Similar values of delta(15) N-NO3 (-) and delta(18) O in RF suggested similar source of atmospheric NO3 (-) (i.e. local traffic), while more positive values for delta(15) N-NH4 (+) at HN compared to LN likely reflected the contribution of dry NHx deposition from intensive local farming. The isotopic signatures of the N-forms changed after interacting with tree canopies. Indeed, (15) N-enriched NH4 (+) in TF compared to RF at all sites suggested that canopies played an important role in buffering dry Ndep also at the low Ndep site. Using two independent methods, based on delta(18) O and Delta(17) O, we quantified for the first time the proportion of NO3 (-) in TF, which derived from nitrification occurring in tree canopies at the HN site. Specifically, for Scots pine, all the considered isotope approaches detected biological nitrification. By contrast for the beech, only using the mixing model with Delta(17) O, we were able to depict the occurrence of nitrification within canopies. Our study suggests that tree canopies play an active role in the N cycling within forest ecosystems. Processing of Ndep within canopies should not be neglected and needs further exploration, with the combination of multiple isotope tracers, with particular reference to Delta(17) O. PMID- 26146937 TI - Changes in intracellular ATP-content of CHO cells as response to hyperosmolality. AB - A variety of approaches has been published to enhance specific productivity (qp) of recombinant Chinese hamster ovary (CHO) cells. Changes in culture conditions, e. g. temperature shifts, sodium butyrate treatment and hyperosmolality, were shown to improve qp . To contribute to a better understanding of the correlation between hyperosmolality and enhanced qp , we analyzed cellular kinetics and intracellular adenine nucleotide pools during osmotic shift periods. Known phenotypes like increased formation rates for lactate and product (anti-IL-8 antibody; qlactate, qp) as well as increased cell specific uptake rate for glucose (qglucose ) were found--besides inhibition of cell growth and G1-arrest occurred during batch cultivations with osmotic shift. The analysis of intracellular AXP pools revealed enlarged ATP amounts for cells as response to hyperosmolality while energy charges remained unchanged. Enhanced ATP-pools coincided with severely increased ATP formation rates (qATP ) which outweighed by far the putative requirements attributed to regulatory volume increase. Therefore elevated qATP mirrored an increased cellular demand for energy while experiencing hyperosmotic shift. PMID- 26146938 TI - Ontogenetic and static allometry in the human face: contrasting Khoisan and Inuit. AB - OBJECTIVES: Regional differences in modern human facial features are present at birth, and ontogenetic allometry contributes to variation in adults. However, details regarding differential rates of growth and timing among regional groups are lacking. We explore ontogenetic and static allometry in a cross-sectional sample spanning Africa, Europe and North America, and evaluate tempo and mode in two regional groups with very different adult facial morphology, the Khoisan and Inuit. MATERIALS AND METHODS: Semilandmark geometric morphometric methods, multivariate statistics and growth simulations were used to quantify and compare patterns of facial growth and development. RESULTS: Regional-specific facial morphology develops early in ontogeny. The Inuit has the most distinct morphology and exhibits heterochronic differences in development compared to other regional groups. Allometric patterns differ during early postnatal development, when significant increases in size are coupled with large amounts of shape changes. All regional groups share a common adult static allometric trajectory, which can be attributed to sexual dimorphism, and the corresponding allometric shape changes resemble developmental patterns during later ontogeny. DISCUSSION: The amount and pattern of growth and development may not be shared between regional groups, indicating that a certain degree of flexibility is allowed for in order to achieve adult size. In early postnatal development the face is less constrained compared to other parts of the cranium allowing for greater evolvability. The early development of region-specific facial features combined with heterochronic differences in timing or rate of growth, reflected in differences in facial size, suggest different patterns of postnatal growth. PMID- 26146940 TI - Noise promotes independent control of gamma oscillations and grid firing within recurrent attractor networks. AB - Neural computations underlying cognitive functions require calibration of the strength of excitatory and inhibitory synaptic connections and are associated with modulation of gamma frequency oscillations in network activity. However, principles relating gamma oscillations, synaptic strength and circuit computations are unclear. We address this in attractor network models that account for grid firing and theta-nested gamma oscillations in the medial entorhinal cortex. We show that moderate intrinsic noise massively increases the range of synaptic strengths supporting gamma oscillations and grid computation. With moderate noise, variation in excitatory or inhibitory synaptic strength tunes the amplitude and frequency of gamma activity without disrupting grid firing. This beneficial role for noise results from disruption of epileptic-like network states. Thus, moderate noise promotes independent control of multiplexed firing rate- and gamma-based computational mechanisms. Our results have implications for tuning of normal circuit function and for disorders associated with changes in gamma oscillations and synaptic strength. PMID- 26146941 TI - Microautophagy involves programmed cell semi-death of sieve elements in developing caryopsis of Triticum aestivum L. AB - Differentiation of sieve elements (SEs) involves programmed cell semi-death, in which a small amount of organelles is retained. However, the mechanisms by which a large amount of SE cytoplasm is degraded and the specific proteases involved are not clear. In this study, we confirmed that the degradation of cytoplasm outside of the vacuole was mediated by microautophagy of the vacuole, and that the tonoplast selectively fused with the plasma membrane after most of the cytoplasm in the vacuoles was degraded. The integration of space enclosed a small amount of cytoplasm. Therefore, that fraction of the cytoplasm was preserved. At the same time, the cytosol was weakly acidic during membrane fusion because part of the tonoplast was ruptured. We also demonstrated that wheat aspartic protease (WAP1) and proteases including cathepsin B activity (PICA) were involved in programmed cell semi-death of SEs. PICA showed strongest activity before mass of the cytoplasm was degraded, which might contribute toward SE stability. We found that WAP1 mainly degraded the cytoplasm. Therefore, programmed cell semi-death of SEs might result from the joint action of vacuoles and multiple proteases. PMID- 26146939 TI - NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets. AB - We take a functional genomics approach to congenital heart disease mechanism. We used DamID to establish a robust set of target genes for NKX2-5 wild type and disease associated NKX2-5 mutations to model loss-of-function in gene regulatory networks. NKX2-5 mutants, including those with a crippled homeodomain, bound hundreds of targets including NKX2-5 wild type targets and a unique set of "off targets", and retained partial functionality. NKXDeltaHD, which lacks the homeodomain completely, could heterodimerize with NKX2-5 wild type and its cofactors, including E26 transformation-specific (ETS) family members, through a tyrosine-rich homophilic interaction domain (YRD). Off-targets of NKX2-5 mutants, but not those of an NKX2-5 YRD mutant, showed overrepresentation of ETS binding sites and were occupied by ETS proteins, as determined by DamID. Analysis of kernel transcription factor and ETS targets show that ETS proteins are highly embedded within the cardiac gene regulatory network. Our study reveals binding and activities of NKX2-5 mutations on WT target and off-targets, guided by interactions with their normal cardiac and general cofactors, and suggest a novel type of gain-of-function in congenital heart disease. PMID- 26146942 TI - Carbon Dioxide Capture by a Metal-Organic Framework with Nitrogen-Rich Channels Based on Rationally Designed Triazole-Functionalized Tetraacid Organic Linker. AB - A semirigid tetraacid linker H4L functionalized with 1,2,3-triazole was rationally designed and synthesized to access nitrogen-rich MOFs for selective adsorption of CO2. The cadmium MOF, that is, Cd-L, obtained by the reaction of H4L with Cd(NO3)2, is found to be a 3D porous framework structure that is robust to desolvation. Crystal structure analysis reveals channels that are decorated by the triazole moieties of L. Gas adsorption studies show that Cd-L MOF permits remarkable CO2 uptake to the extent of 99 and 1000 cc/g at 1 and 30 bar, respectively, at 0 degrees C. While literature survey reveals that MIL-112, constructed from a 1,2,3-triazole functionalized linker, exhibits no porosity to gas adsorption due to structural flexibility, the results with Cd-L MOF described herein emphasize how rigidification of the organic linker improves gas uptake properties of the resultant MOF. PMID- 26146944 TI - Echocardiographic Detection of Cardiac Dysfunction in Childhood Cancer Survivors: How Long Is Screening Required? AB - BACKGROUND: Childhood cancer survivors treated with anthracycline chemotherapy are at an increased risk of long-term cardiac toxicity, and guidelines recommend that exposed survivors undergo echocardiography every 1-5 years. However, it is unclear whether survivors should undergo echocardiographic screening indefinitely, or if a period of echocardiographic stability indicates that screening is no longer necessary. The objective of this study was to evaluate the outcomes of echocardiographic screening to aid in the refinement of existing guidelines. METHODS: We retrospectively analyzed the results of echocardiographic screening in a cohort of adult survivors of childhood cancer treated with anthracyclines and/or cardiac radiation therapy. Interval regression analysis was performed to identify predictors of single-episode or sustained abnormal echocardiograms. RESULTS: The cohort constituted 333 survivors, with median follow-up time of 15.8 years post-treatment (range: 5.0-47.9), and median age at treatment of 8 years (range: 1.5-18). Forty-nine survivors had an abnormal echocardiogram (14.7%), and 29 (8.7%) had reproducible abnormal findings. An ongoing continual increase in the incidence of sustained echocardiographic abnormality was seen among patients treated with >250 mg/m(2) doxorubicin at age <5 years, reaching 43% by 20 years of therapy. In contrast, no sustained abnormal echocardiographic findings arose after 10 years of therapy in survivors treated with <250 mg/m(2) at age >=5 years. CONCLUSIONS: Single-episode echocardiographic abnormalities are often not reproduced in subsequent evaluations. The duration of echocardiographic screening for childhood cancer survivors should be reassessed for patients who received lower doses of anthracycline after age 5. PMID- 26146945 TI - RIG-I is required for VSV-induced cytokine production by murine glia and acts in combination with DAI to initiate responses to HSV-1. AB - A defining feature of viral central nervous system (CNS) infection is the rapid onset of severe neuroinflammation. However, the mechanisms underlying glial responses to replicative neurotropic viruses are only now becoming apparent with the discovery of a number of cytosolic sensors for viral nucleic acids. We have described the expression by murine and human glial cells of two disparate pattern recognition receptors, retinoic acid inducible gene-I (RIG-I) and DNA-dependent activator of interferon regulatory factors (DAI), receptors for viral RNA and DNA moieties, respectively. In the present study, we demonstrate the functional significance of RIG-I expression in primary murine microglia and astrocytes. Our data indicate that murine glial immune responses to a model neurotropic RNA virus, vesicular stomatitis virus, are RIG-I dependent and independent of levels of DAI expression or RNA polymerase III activity. In contrast, maximal glial inflammatory and antiviral responses to the DNA virus herpes simplex virus-1 (HSV 1) are dependent on the expression of both RIG-I and DAI, and require RNA polymerase III activity. These findings indicate that the RNA sensor, RIG-I, acts in parallel with DAI in an RNA polymerase III-dependent manner to initiate glial responses to HSV-1. We therefore suggest that RIG-I plays a significant role in the detection of both RNA and DNA pathogens by microglia and astrocytes. PMID- 26146946 TI - Structure and validity of Family Harmony Scale: An instrument for measuring harmony. AB - Culture plays a role in mental health, partly by defining the characteristics that are indicative of positive adjustment. In Chinese cultures, positive family relationships are considered central to well-being. The culturally emphasized characteristic of family harmony may be an important factor associated with psychopathology. This article presents the development and psychometric examination of the Family Harmony Scale (FHS), an indigenously developed 24-item instrument tapping family harmony in 17,461 Hong Kong residents from 7,791 households. A higher-order model with 1 second-order factor and 5 first-order factors fit the data well and showed factorial invariance across sex and participants in different family roles. A 5-item short form (FHS-5) was also developed, with 1 item from each first-order factor. The short scale showed, as expected, a single-factor structure with good fit. Both scales demonstrated high internal consistency, acceptable test-retest reliability, and good convergent and discriminant validity. The 24-item FHS was negatively associated with depressive symptoms after accounting for individual risk factors and general family function. Family harmony moderated the relationship between life stress and depressive symptoms such that those individuals who reported low family harmony had stronger associations between life stress and depressive symptoms. This study adds to the literature a systematically developed, multidimensional measure of family harmony, which may be an important psychological protective factor, in a large urban Chinese sample. The FHS-5 minimizes operational and respondent burdens, making it an attractive tool for large-scale epidemiological studies with Chinese populations in urban settings, where over half of China's 1.4 billion people reside. PMID- 26146947 TI - All-data approach to assessing financial capability in people with psychiatric disabilities. AB - The goal of this project was to develop an evidence-based method to assess the ability of disabled persons to manage federal disability payments. This article describes the development of the Financial Incapability Structured Clinical Assessment done Longitudinally (FISCAL) measure of financial capability. The FISCAL was developed by an iterative process of literature review, pilot testing, and expert consultation. Independent assessors used the FISCAL to rate the financial capability of 118 participants (57% female, 58% Caucasian) who received Social Security disability payments, had recently been treated in acute care facilities for psychiatric disorders, and who did not have representative payees or conservators. Altogether, 48% of participants were determined financially incapable by the FISCAL, of whom 60% were incapable because of unmet basic needs, 91% were incapable because of spending that harmed them (e.g., on illicit drugs or alcohol), 56% were incapable because of both unmet needs and harmful spending, and 5% were incapable because of contextual factors. As expected, incapable individuals scored higher on a measure of money mismanagement (p < .001) compared with capable individuals. Interrater reliability for FISCAL capability determinations was very good (kappa = .77) and interrater agreement was 89%. In this population, the FISCAL had construct validity; ratings demonstrated good reliability and correlated with a related measure. Potentially, the FISCAL can be used to validate other measures of capability and to help understand how people on limited incomes manage their funds. PMID- 26146949 TI - Cross-informant and cross-national equivalence using item-response theory (IRT) linking: A case study using the behavioral assessment for children of African heritage in the United States and Jamaica. AB - Cross-national study of adolescents' psychological adjustment requires measures that permit reliable and valid assessment across informants and nations, but such measures are virtually nonexistent. Item-response-theory-based linking is a promising yet underutilized methodological procedure that permits more accurate assessment across informants and nations. To demonstrate this procedure, the Resilience Scale of the Behavioral Assessment for Children of African Heritage (Lambert et al., 2005) was administered to 250 African American and 294 Jamaican nonreferred adolescents and their caregivers. Multiple items without significant differential item functioning emerged, allowing scale linking across informants and nations. Calibrating item parameters via item response theory linking can permit cross-informant cross-national assessment of youth. PMID- 26146948 TI - Assessing the Everyday Discrimination Scale among American Indians and Alaska Natives. AB - The Everyday Discrimination Scale (EDS) has been used widely as a measure of subjective experiences of discrimination. The usefulness of this measure for assessments of perceived experiences of discrimination by American Indian and Alaska Native (AI/AN) peoples has not been explored. Data derived from the Special Diabetes Program for Indians--Healthy Heart Demonstration Project (SDPI HH), a large-scale initiative to reduce cardiovascular risk among AI/ANs with Type 2 diabetes. Participants (N = 3,039) completed a self-report survey that included the EDS and measures of convergent and divergent validity. Missing data were estimated by multiple imputation techniques. Reliability estimates for the EDS were calculated, yielding a single factor with high internal consistency (alpha = .92). Younger, more educated respondents reported greater perceived discrimination; retired or widowed respondents reported less. Convergent validity was evidenced by levels of distress, anger, and hostility, which increased as the level of perceived discrimination increased (all p < .001). Divergent validity was evidenced by the absence of an association between EDS and resilient coping. Resilient coping and insulin-specific diabetes knowledge were not significantly associated with perceived discrimination (p = .61 and 0.16, respectively). However, general diabetes-related health knowledge was significantly associated with perceived discrimination (p = .02). The EDS is a promising measure for assessing perceived experiences of discrimination among those AI/ANs who participated in the SDPI-HH. PMID- 26146950 TI - Do neuropsychological test norms from African Americans in the United States generalize to a Zambian population? AB - Healthy Zambian adults (N = 324) were evaluated to determine to what degree a Western neuropsychological (NP) test battery, with African American norms adjusted for age, gender, and education could be used in healthy Zambians, including 157 men (48.46%) and 167 women (51.54%) with an average age of 38.48 (SD = 12.80) years and an average education level of 11.02 (SD = 2.58) years. The NP battery included tests of attention/working memory, executive function, verbal fluency, processing speed, verbal and visual episodic memory, and fine motor skills. The Zambian Achievement Test (ZAT) and the U.S. Wide Range Achievement Test-4 (WRAT-4) reading subtest also were administered to assess literacy and quality of education. Similar to findings in Western countries, the Zambian results show substantial age and education effects on most tests and smaller, less consistent effects of gender. Beyond the basic demographic effects, urban/rural background had small effects on some cognitive variables, and the ZAT (but not WRAT-4) reading level was a robust predictor of performance on many NP tests, even when other background characteristics were controlled. Women in the United States tend to outperform men on tests of processing speed and episodic memory. However, Zambian women showed modest but statistically significant disadvantages versus their male counterparts. The results show that tests developed in the United States may be used in Zambia. Nevertheless, development and use of local cultural norms remains very important and is a must. New demographically corrected norms were developed for the cohort that was examined. PMID- 26146951 TI - The utility of the Psychopathy Checklist: Youth Version (PCL: YV) and the Youth Psychopathic Trait Inventory (YPI)--Is it meaningful to measure psychopathy in young offenders? AB - This study examined the convergent validity of 2 youth psychopathy instruments, the Psychopathy Checklist: Youth Version (PCL: YV) and the Youth Psychopathic Trait Inventory (YPI) and their relationship with problem behaviors and recidivism in an Australian sample of young offenders in custody. The PCL: YV demonstrated a capacity to identify severely antisocial youth; however, the tool was unable to differentiate between potentially psychopathic and nonpsychopathic antisocial youth. The YPI was receptive to a wide variety of problem behaviors which precluded the unique identification of core psychopathic traits in the sample. Both instruments were unable to meaningfully distinguish between recidivists and nonrecidivists. As such, the PCL: YV and the YPI demonstrate limited utility for antisocial young offenders in custody. Further research on the durability and developmental manifestation of psychopathy in adolescents is necessary before these instruments are employed in similar contexts. Implications for the clinical use of psychopathy measures are discussed. PMID- 26146952 TI - Elusive Structural, Functional, and Immunological Features of Act d 5, the Green Kiwifruit Kiwellin. AB - Kiwellin (Act d 5) is an allergenic protein contained in kiwifruit pulp in high amounts. The aim of this study was to investigate the three-dimensional structure of the natural molecule from green kiwifruit and its possible function. Kiwellin was crystallized, and its structure, including post-translational modifications, was elucidated. The molecular weight and structural features, in solution, were analyzed by gel filtration and circular dichroism, respectively. Although structurally similar to expansin, kiwellin lacks expansin activity and carbohydrate binding. A specific algorithm was applied to investigate any possible IgE reactivity correlation between kiwellin and a panel of 102 allergens, including expansins and other carbohydrate-binding allergens. The available data suggest a strong dependence of the kiwellin structure on the environmental/experimental conditions. This dependence therefore poses challenges in detecting the correlations between structural, functional, and immunological features of this protein. PMID- 26146953 TI - Cheerios Effect Controlled by Electrowetting. AB - The Cheerios effect is a common phenomenon in which small floating objects are either attracted or repelled by the sidewall due to capillary interaction. This attractive or repulsive behavior is highly dependent on the slope angles (angles of the interface on the wall or floating object with respect to a horizontal line) that can be mainly controlled by the wettability of the wall and floating object and the density of the object. In this paper, electrowetting on dielectric (EWOD) is implemented to the wall or floating object in order to actively control the wettability and thus capillary interaction. As such, the capillary force on buoyant and dense floating objects can be easily switched between repulsion and attraction by simply applying an electrical input. In addition, the theoretical prediction for the capillary force is verified experimentally by measuring the motion of floating particle and the critical contact angle on the wall at which the capillary force changes from attraction to repulsion. This successive verification is enabled by the merit of EWOD that allows for continuous change in the contact angle. Finally, the control method is extended to continuously move a floating object along a linear path and to continuously rotate a dumbbell-like floating object in centimeter scales using arrays of EWOD electrodes. A continuous linear motion is also accomplished in a smaller scale where the channel width (3 mm) is comparable to the capillary length. PMID- 26146954 TI - Prenatal Exposure to Bisphenol A Disrupts Mouse Fetal Liver Maturation in a Sex Specific Manner. AB - Bisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals in the environment. Developmental exposure to BPA is known to be associated with liver dysfunction and diseases, such as hepatic steatosis, liver tumors, metabolic syndrome, and altered hepatic gene expression, and DNA methylation profiles. However, the effects of BPA on rodent liver development are unknown. The present study was undertaken to address this important question using the mouse as an experimental model. Pregnant mice were exposed to BPA via diet from embryonic day 7.5 (E7.5) to E18.5. At E18.5, fetal livers were collected, and analyzed for changes in the expression of key hepatocyte maturation markers. We found the following significant alterations in BPA-exposed female but not male fetal livers: (a) levels of the mature hepatocyte markers, albumin and glycogen synthase proteins, were decreased (-65% and -40%, respectively); (b) levels of the immature hepatocyte marker, alpha-fetoprotein, were increased (+43%); (c) the level of C/EBP-alpha protein, the master transcription factor essential for hepatocyte maturation, was down-regulated (-50%); and (d) the level of PCNA protein (marker of proliferation) was elevated (+40%), while that of caspase-3 protein and activity (markers of apoptosis) was reduced (-40% and -55%, respectively), suggestive of a perturbed balance between cell proliferation and apoptosis in BPA-exposed female fetuses. Taken together, these findings demonstrate that prenatal exposure to BPA disrupts the mouse fetal liver maturation in a sex-specific manner, and suggest a fetal origin for BPA-induced hepatic dysfunction and diseases. PMID- 26146955 TI - Mapping Protein Conformational Landscapes under Strongly Native Conditions with Hydrogen Exchange Mass Spectrometry. AB - The thermodynamic stability and kinetic barriers separating protein conformations under native conditions are critical for proper protein function and for understanding dysfunction in diseases of protein conformation. Traditional methods to probe protein unfolding and folding employ denaturants and highly non native conditions, which may destabilize intermediate species or cause irreversible aggregation, especially at the high protein concentrations typically required. Hydrogen exchange (HX) is ideal for detecting conformational behavior under native conditions without the need for denaturants, but detection by NMR is limited to small highly soluble proteins. Mass spectrometry (MS) can, in principle, greatly extend the applicability of native-state HX to larger proteins and lower concentrations. However, quantitative analysis of HXMS profiles is currently limited by experimental and theoretical challenges. Here we address both limitations, by proposing an approach based on using standards to eliminate the systematic experimental artifacts in HXMS profiles, and developing the theoretical framework to describe HX behavior across all regimes based on the Linderstrom-Lang formalism. We demonstrate proof of principle by a practical application to native-state HX of a globular protein. The framework and the practical tools developed advance the ability of HXMS to extract thermodynamic and kinetic conformational parameters of proteins under native conditions. PMID- 26146956 TI - On the nuclear halo of a proton pencil beam stopping in water. AB - The dose distribution of a proton beam stopping in water has components due to basic physics and may have others from beam contamination. We propose the concise terms core for the primary beam, halo (see Pedroni et al 2005 Phys. Med. Biol. 50 541-61) for the low dose region from charged secondaries, aura for the low dose region from neutrals, and spray for beam contamination. We have measured the dose distribution in a water tank at 177 MeV under conditions where spray, therefore radial asymmetry, is negligible. We used an ADCL calibrated thimble chamber and a Faraday cup calibrated integral beam monitor so as to obtain immediately the absolute dose per proton. We took depth scans at fixed distances from the beam centroid rather than radial scans at fixed depths. That minimizes the signal range for each scan and better reveals the structure of the core and halo. Transitions from core to halo to aura are already discernible in the raw data. The halo has components attributable to coherent and incoherent nuclear reactions. Due to elastic and inelastic scattering by the nuclear force, the Bragg peak persists to radii larger than can be accounted for by Moliere single scattering. The radius of the incoherent component, a dose bump around midrange, agrees with the kinematics of knockout reactions. We have fitted the data in two ways. The first is algebraic or model dependent (MD) as far as possible, and has 25 parameters. The second, using 2D cubic spline regression, is model independent. Optimal parameterization for treatment planning will probably be a hybrid of the two, and will of course require measurements at several incident energies. The MD fit to the core term resembles that of the PSI group (Pedroni et al 2005), which has been widely emulated. However, we replace their T(w), a mass stopping power which mixes electromagnetic (EM) and nuclear effects, with one that is purely EM, arguing that protons that do not undergo hard single scatters continue to lose energy according to the Beth-Bloch formula. If that is correct, it is no longer necessary to measure T(w), and the dominant role played by the 'Bragg peak chamber' vanishes. For mathematical and other details we will refer to Gottschalk et al (2014, arXiv: 1409.1938v1), a long technical report of this project. PMID- 26146957 TI - 2D-GaS as a Photocatalyst for Water Splitting to Produce H2. AB - Using first-principles local and hybrid density functional theoretical calculations, a thickness-dependent electronic structure of layered GaS is determined, and it is shown that 2D GaS has an electronic structure with valence and conduction bands that straddle the redox potentials of hydrogen evolution reaction and oxygen evolution reaction up to a critical thickness (<5.5 nm). Here, simulations of adsorption of H2O on nanoscale GaS reveal that localized electronic states at its edges appear in the gap and strengthen the interaction with H2O, further activating the surface atomic sites. It is thus predicted that GaS synthesized with a controlled thickness and preferred edges may be an efficient catalyst for photocatalytic splitting of water. Experiments that verify some of the predictions in this study are presented, and it is shown that GaS is effective in absorption of light and evolution of H2 (887 MUmol h(-1) g(-1)) in the presence of aqueous solution of hydrazine (1% v/v). This study should open up the use of nanoscale GaS in conversion of solar energy into environment-friendly chemical energy in the form of hydrogen. PMID- 26146958 TI - Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer. AB - Tremendous efforts have been made to develop cancer biomarkers by detecting circulating extracellular miRNAs directly released from tumors. Yet, none of the cell-free biomarkers has been accepted to be used for early detection of non small cell lung cancer (NSCLC). Peripheral blood mononucleated cells (PBMCs) act as the first line of defense against malignancy in immune system, their dysfunction may occur as an early event in cancer immunogenicity or immune evasion. We proposed to investigate whether analysis of miRNA expressions of PBMCs has diagnostic value for NSCLC. We first used a microarray to analyze PBMCs of 16 stage I NSCLC patients and 16 cancer-free smokers, and identified seven PBMC miRNAs with a significantly altered expression level in NSCLC patients. In a training set of 84 NSCLC patients and 69 cancer-free smokers, a panel of two miRNAs (miRs-19b-3p and -29b-3p) were developed from the seven PBMC miRNAs, producing 72.62% sensitivity and 82.61% specificity in identifying NSCLC. Furthermore, the miRNAs could identify squamous cell lung carcinoma (SCC), a major type of NSCLC, with 80.00% sensitivity and 89.86% specificity. The expression levels of the miRNAs were independent of disease stage. In a testing set of 56 NSCLC patients and 46 controls, the performance of the biomarkers was reproducibly confirmed. The study presents the first in-depth analysis of PBMC miRNA profile of NSCLC patients. The assessment of PBMC miRNAs may provide a new diagnostic approach for the early detection of NSCLC. PMID- 26146959 TI - KRAS(G12D)-mediated oncogenic transformation of thyroid follicular cells requires long-term TSH stimulation and is regulated by SPRY1. AB - KRAS(G12D) can cause lung cancer rapidly, but is not sufficient to induce thyroid cancer. It is not clear whether long-term serum thyroid stimulating hormone (TSH) stimulation can promote KRAS(G12D)-mediated thyroid follicular cell transformation. In the present study, we investigated the effect of long-term TSH stimulation in KRAS(G12D) knock-in mice and the role of Sprouty1 (SPRY1) in KRAS(G12D)-mediated signaling. We used TPO-KRAS(G12D) mice for thyroid-specific expression of KRAS(G12D) under the endogenous KRAS promoter. Twenty TPO KRAS(G12D) mice were given anti-thyroid drug propylthiouracil (PTU, 0.1% w/v) in drinking water to induce serum TSH and 20 mice were without PTU treatment. Equal number of wild-type littermates (TPO-KRAS(WT)) was given the same treatment. The expression of SPRY1, a negative regulator of receptor tyrosine kinase (RTK) signaling, was analyzed in both KRAS(G12D)-and BRAF(V600E)-induced thyroid cancers. Without PTU treatment, only mild thyroid enlargement and hyperplasia were observed in TPO-KRAS(G12D) mice. With PTU treatment, significant thyroid enlargement and hyperplasia occurred in both TPO-KRAS(G12D) and TPO-KRAS(WT) littermates. Thyroids from TPO-KRAS(G12D) mice were six times larger than TPO KRAS(WT) littermates. Distinct thyroid histology was found between TPO-KRAS(G12D) and TPO-KRAS(WT) mice: thyroid from TPO-KRAS(G12D) mice showed hyperplasia with well-maintained follicular architecture whereas in TPO-KRAS(WT) mice this structure was replaced by papillary hyperplasia. Among 10 TPO-KRAS(G12D) mice monitored for 14 months, two developed follicular thyroid cancer (FTC), one with pulmonary metastasis. Differential SPRY1 expression was demonstrated: increased in FTC and reduced in papillary thyroid cancer (PTC). The increased SPRY1 expression in FTC promoted TSH-RAS signaling through PI3K/AKT pathway whereas downregulation of SPRY1 by BRAF(V600E) in PTC resulted in both MAPK and PI3K/AKT activation. We conclude that chronic TSH stimulation can enhance KRAS(G12D) mediated oncogenesis, leading to FTC. SPRY1 may function as a molecular switch to control MAPK signaling and its downregulation by BRAF(V600E) favors PTC development. PMID- 26146961 TI - Hybrid, multiplexed, functional DNA nanotechnology for bioanalysis. AB - We herein aim to report on the fabrication of DNA nano-heterostructures usable as a robust multi-functional analytical system to obtain multiple and complex data in parallel format from a single sample with unprecedented analytical performances. The ability of chemical information contained in the sequences of programmed DNA structures to organize matter made DNA become a unique material in "the nanoworld". Such carefully designed DNA nanostructures can then be functionalized/templated with different biomolecules/nanomaterials as different as nanoparticles, nanowires, organic molecules, peptides, and proteins with controlled spacing on the nanometer scale (<10 nm). In this way, it is possible to combine the properties of both DNA and nanomaterials for exposing the designed functionality and customizable geometrical hetero-nanostructures. By coupling automated on-chip high yield DNA synthesis with low cost detection methods, DNA nanotechnology can enable the realization of high-sensitivity, multiplexed bioanalytical assays for many different applications like diagnostics, drug screening, toxicology, immunology and biosensors. PMID- 26146960 TI - Galectin 3 regulates HCC cell invasion by RhoA and MLCK activation. AB - Hepatocellular carcinoma (HCC) carries a poor prognosis with no effective treatment available other than liver transplantation for selected patients. Vascular invasion of HCC is one of the most important negative predictor of survival. As the regulation of invasion of HCC cells is not well understood, our aim was to study the mechanisms by which galectin 3, a beta-galactosidase-binding lectin mediates HCC cell migration. HCC was induced by N-diethylnitrosamine in wild-type and galectin 3(-/-) mice, and tumor formation, histology, and tumor cell invasion were assessed. The galectin 3(-/-) mice developed significantly smaller tumor burden with a less invasive phenotype than the wild-type animals. Galectin 3 was upregulated in the wild-type HCC tumor tissue, but not in the surrounding parenchyma. Galectin 3 expression in HCC was induced by NF-kappaB transactivation as determined by chromatin immunoprecipitation assays. In vitro studies assessed the pro-migratory effects of galectin 3. The migration of hepatoma cells was significantly decreased after transfection by the galectin 3 siRNA and also after using the Rho kinase inhibitor Y-27632. The reorganization of the actin cytoskeleton, RhoA GTPase activity and the phosphorylation of MLC2 (myosin light chain 2) were decreased in the galectin 3 siRNA-transfected cells. In addition, in vitro and in vivo evidence showed that galectin 3 deficiency reduced hepatoma cell proliferation and increased their apoptosis rate. In conclusion, galectin 3 is an important lectin that is induced in HCC cells, and promotes hepatoma cell motility and invasion by an autocrine pathway. Targeting galectin 3 therefore could be an important novel treatment strategy to halt disease progression. PMID- 26146962 TI - Screening for incontinence in a secure psychiatric service for women. AB - Incontinence is associated with mental illness and neuroleptic medications but diagnosis and treatment is often poor or non-existent. Problems of incontinence are compounded in secure psychiatric services for women by poor health, obesity, and a sedentary lifestyle. Addressing the physical health of this group necessitates a more accurate picture of the nature, incidence, and management of incontinence. A point-in-time survey of 108 women who agreed to be interviewed (93%) covered presence, frequency, and nature of incontinence, and information on management case note data was used to gather demographic and previous medical history, comparisons were made between patients with and without problems of incontinence. Findings indicate a problem of incontinence in 48% of women with a dominance of problems of stress and urge enuresis. Of modifiable factors that contribute to enuresis, the current study highlighted the contribution of obesity, smoking and clozapine medication. A further finding was the preference for managing rather than treating problems of incontinence. Actions to improve the detection and treatment of this problem are described. PMID- 26146963 TI - Hyperbaric oxygen therapy for refractory radiation-induced hemorrhagic cystitis. AB - OBJECTIVES: To analyze the efficacy of hyperbaric oxygen for the treatment of radiation-induced hemorrhagic cystitis and to identify factors associated with successful treatment. METHODS: Clinical records from 176 patients with refractory radiation-induced hemorrhagic cystitis treated at the Portuguese Navy Center for Underwater and Hyperbaric Medicine, during a 15-year period, were retrospectively analyzed. Evolution of macroscopic hematuria was used to analyze treatment efficacy and correlated with other external variables. RESULTS: From a total of 176 treated patients, 23.9% evidenced other radiation-induced soft tissue lesions. After an average on 37 sessions, 89.8% of patients showed resolution of hematuria, with only 1.7% of adverse events. In our sample, hematuria resolution after treatment with hyperbaric oxygen was statistically associated to the need for transfusion therapy (P = 0.026) and the number of sessions of hyperbaric oxygen (P = 0.042). No relationship was found with the remaining variables. CONCLUSIONS: Refractory radiation-induced hemorrhagic cystitis can be successfully and safely treated with hyperbaric oxygen. Treatment effectiveness seems to be correlated with the need for transfusion therapy and the number of sessions performed. PMID- 26146965 TI - Does muscle size matter? PMID- 26146966 TI - Lateral Ankle Stabilization Using Acellular Human Dermal Allograft Augmentation. AB - BACKGROUND: We describe a retrospective study that uses the Brostrom-type surgical procedure with modifications that augment deficient and torn ligaments with acellular human dermal grafts. At the onset of this study, the most prevalent dermal graft available to us was GraftJacket (Wright Medical Technology, Arlington, Tennessee). Greater than 50% of the study participants were grafted with this product, but more recently other equally effective human dermal grafts have been used with no apparent difference. METHODS: Thirty-five lateral ankle stabilization procedures were performed in the past 6 years on 33 patients. Eight patients were considered athletes (mean age, 23 years). The balance of the study group consisted of sedentary patients (mean age, 41 years). The mean patient body mass index (calculated as the weight in kilograms divided by the square of the height in meters) was 31. RESULTS: All of the patients were satisfied with their results, with no recurrent instability. Two patients in this group went on to have contralateral ankle stabilization in a similar manner owing to their satisfaction. Complications included two soft-tissue infections. CONCLUSIONS: Lateral ankle stabilization using acellular human dermal graft augmentation is a useful tool in the surgical treatment of ankle instability. This procedure offers distinct advantages over traditional methods of ankle repair and can be performed with relatively limited surgical exposure. Ease of operation, consistent results, and limited patient morbidity should allow surgeons to use this procedure independently or adjunctively to improve surgical outcomes. PMID- 26146964 TI - An exploratory analysis of the self-reported goals of individuals with chronic upper-extremity paresis following stroke. AB - PURPOSE: To classify the self-identified goals of individuals post-stroke with chronic upper extremity (UE) paresis, and determine if age, UE functional capacity and pre-stroke hand dominance influence overall goal selection. METHOD: Sixty-five subjects participated. Using the Canadian Occupational Performance Measure (COPM) to establish treatment goals, the top five goals were categorized using the Occupational Therapy Practice Framework into five categories: activities of daily living (ADLs), instrumental activities of daily living (IADLs), leisure, work and general UE movement. A Chi-square analysis determined if age, UE functional capacity (measured by the Action Research Arm Test) and UE hand dominance influenced individual goal selection. RESULTS: The majority of goals were in the ADL (37%) and IADL (40%) categories. A small percentage (12%) was related to general UE movement. Individuals with moderate UE functional capacity identified more ADL goals than those with higher UE functional capacity. There was not a difference between age and UE dominance across all five goal areas. CONCLUSIONS: Individuals with chronic UE paresis had specific goals that were not influenced by age or hand dominance, but partially influenced by severity. General UE movement goals were identified less than goals related to specific activities. IMPLICATIONS FOR REHABILITATION: Considering the specificity of individual goals following stroke, it is recommended that clinicians regularly utilize a goal setting tool to help establish client goals. It is recommended that clinicians further inquire about general goals in order to link upper extremity deficits to functional activity limitations. Age, upper extremity functional capacity and hand dominance have little influence on the rehabilitation goals for individuals with chronic paresis after stroke. PMID- 26146967 TI - Comparison of Barefoot Walking and Shod Walking Between Children with and Without Flat Feet. AB - BACKGROUND: We sought to investigate the effect of wearing shoes on joint range of motion, ground reaction force (GRF), and muscle activity (electromyography) in children with flat and normal feet during walking. METHODS: Nine children with flat feet and 12 children with normal feet aged 5 to 11 years were recruited. Each child was instructed to walk on a walkway in the barefoot and shod conditions. Joint range of motion, GRF, and electromyographic data within one gait cycle were collected simultaneously. Two-way analysis of variance was performed to evaluate the effects of foot type and shoe condition on the response measures. RESULTS: Children with flat feet had greater joint motion and higher muscle activities in the lower extremity, as well as lower vertical GRF and longer duration of the first peak forces in vertical and mediolateral GRFs than children with normal feet while walking. Compared with the barefoot condition, shoe wearing in both groups of children showed an increase in ankle dorsiflexion at heel strike, a decrease in anteroposterior GRF and its duration, and an increase in leg muscle electromyographic activities. Pelvic tilt range of motion was affected by the interaction of foot type and shoe condition. CONCLUSIONS: Gait performance in pelvic tilt, hip flexion, and ankle dorsiflexion were different between the two groups of children. Wearing shoes increased the muscle activities of the shin. This finding can provide important information for clinical assessment of and shoe design for children with flat feet. PMID- 26146968 TI - Reliability and Validity of the Footprint Assessment Method Using Photoshop CS5 Software. AB - BACKGROUND: Several sophisticated methods of footprint analysis currently exist. However, it is sometimes useful to apply standard measurement methods of recognized evidence with an easy and quick application. We sought to assess the reliability and validity of a new method of footprint assessment in a healthy population using Photoshop CS5 software (Adobe Systems Inc, San Jose, California). METHODS: Forty-two footprints, corresponding to 21 healthy individuals (11 men with a mean +/- SD age of 20.45 +/- 2.16 years and 10 women with a mean +/- SD age of 20.00 +/- 1.70 years) were analyzed. Footprints were recorded in static bipedal standing position using optical podography and digital photography. Three trials for each participant were performed. The Hernandez Corvo, Chippaux-Smirak, and Staheli indices and the Clarke angle were calculated by manual method and by computerized method using Photoshop CS5 software. Test retest was used to determine reliability. Validity was obtained by intraclass correlation coefficient (ICC). RESULTS: The reliability test for all of the indices showed high values (ICC, 0.98-0.99). Moreover, the validity test clearly showed no difference between techniques (ICC, 0.99-1). CONCLUSIONS: The reliability and validity of a method to measure, assess, and record the podometric indices using Photoshop CS5 software has been demonstrated. This provides a quick and accurate tool useful for the digital recording of morphostatic foot study parameters and their control. PMID- 26146969 TI - An Overlooked Deformity in Patients with Hallux Valgus Tailor's Bunion. AB - BACKGROUND: Tailor's bunion is a deformity of the fifth toe, and its concomitance with hallux valgus (HV) is defined as splayfoot deformity. Treatment is focused on the HV deformity in splayfoot, and the tailor's bunion deformity can be overlooked. The frequency of HV concomitant with tailor's bunion in splayfoot has not been reported in the literature. METHODS: A retrospective evaluation was performed to detect the existence of tailor's bunion deformity in 203 patients (376 feet) treated for HV. Standing anteroposterior and lateral radiographs were used in the radiologic evaluation. Fallat's classification was used to grade tailor's bunion. Surgery for HV was applied to 86 patients (136 feet), and conservative treatment was applied to 117 patients (240 feet). Mean follow-up was 28.3 months (range, 18-42 months). Clinical evaluation was by American Orthopaedic Foot and Ankle Society (AOFAS) score. RESULTS: Of the 376 feet with HV, 28 (7.4%) had tailor's bunion, of which 17 (60.7%) were overlooked according to the surgery criteria for tailor's bunion. In the HV surgery group, there were no differences in preoperative mean AOFAS scores according to concurrence with tailor's bunion, but postoperative AOFAS scores were low in patients with accompanying tailor's bunion (P < .001). In the conservative group, no differences were determined in mean AOFAS scores according to tailor's bunion. CONCLUSIONS: Tailor's bunion deformity sometimes goes undiagnosed in patients with treated HV. This deformity must be kept in mind for patients with HV to improve clinical results. PMID- 26146970 TI - Diabetes Management and Its Association with Transtibial Amputation. AB - BACKGROUND: Transtibial (TTA) and transfemoral (TFA) amputations are rarely considered as distinct events when examining major lower-limb amputation outcomes. The objective of this study was to investigate the relationships among type 2 diabetes, diabetes management strategies, hemoglobin A1c levels, and other health factors related to TTA and TFA. METHODS: The retrospective medical record review included abstracting demographic and health-related data from the electronic medical records of 92 patients who received amputation-related services in a Department of Veterans Affairs hospital. RESULTS: Patients who controlled their diabetes with insulin (with or without other oral agents) were significantly more likely to undergo TTA (adjusted odds ratio [aOR] = 7.63; 95% confidence interval [CI], 1.17-49.97; P = .03) compared with patients who controlled their diabetes through noninsulin medications or by diet. Patients who underwent no previous surgery (aOR = 6.66; 95% CI, 0.89-49.72; P = .06) or partial amputation only (aOR = 15.44; 95% CI, 1.04-228.29; P = .05) compared with a combination of partial amputation and bypass, thrombolectomy, or stent procedures were marginally to statistically significantly more likely to undergo TTA than TFA. CONCLUSIONS: The preferential association between TTA with insulin dependent diabetes and higher hemoglobin A1c levels versus TFA with previous lower-limb bypasses, stent placement, and thrombolytic interventions distinguishes TTA and TFA as two distinct entities, and awareness of this difference may help clinicians design preventive strategies accordingly. PMID- 26146971 TI - Linezolid-Associated Serotonin Syndrome. A Report of Two Cases. AB - Linezolid, a mild monoamine oxidase inhibitor, is a commonly used antibiotic drug for the treatment of complicated skin and skin structure infections, including diabetic foot infections. Use of linezolid has been associated with serotonin syndrome, a potentially life-threatening condition typically caused by the combination of two or more medications with serotonergic properties, due to increased serotonin release. The goals of this article are to highlight the risk factors associated with the development of serotonin syndrome related to the use of linezolid and to aid in its prevention and early diagnosis. In this case series we report on two hospitalized patients who, while being treated with linezolid for pedal infections, developed serotonin syndrome. Both individuals were also undergoing treatment with at least one serotonergic agent for depression and had received this medication within 2 weeks of starting the antibiotic drug therapy. In these individuals, we noted agitation, confusion, tremors, and tachycardia within a few days of initiation of linezolid therapy. Owing to the risk of serotonin toxicity, care should be taken when prescribing linezolid in conjunction with any other serotonergic agent. Although serotonin syndrome is an infrequent complication, it can be potentially life threatening. Therefore, risks and benefits of therapy should be weighed before use. PMID- 26146972 TI - Giant Cell Tumor of the Tendon Sheath Around the Foot and Ankle. A Report of Three Cases and a Literature Review. AB - The foot and ankle are rare sites of involvement for giant cell tumor of tendon sheath. We present three rare cases of giant cell tumor of tendon sheath arising from the tendon sheaths of the flexor hallucis longus, peroneus brevis, and extensor hallucis brevis tendons, along with a literature review of such cases in the foot and ankle region. All of the patients were treated with surgical excision of the mass and were asymptomatic after minimum follow-up of 18 months. Giant cell tumor of tendon sheath involving the foot and ankle region is a rare clinical entity, and good results can be expected after surgical excision. PMID- 26146973 TI - A Postaxial Polydactyly with a Partial Duplication of the Fifth Metatarsal Without a Supernumerary Digit. Is Excision of the Duplicated Metatarsal Necessary? AB - Postaxial polydactyly of the foot is one of the most common congenital malformations. Only a few cases of postaxial polydactyly with a partial duplication of the fifth metatarsal without a supernumerary digit have been reported, and both metatarsal heads were united to form a common joint with the proximal phalanx in all of those cases. We present a rare case of postaxial polydactyly with a partial duplication of the fifth metatarsal characterized by dual metatarsal heads and an extra proximal phalanx bud, without a supernumerary digit. PMID- 26146974 TI - Atypical Localization of Enchondroma in the Calcaneus. AB - A 53-year-old man presented to the orthopedic outpatient clinic with pain and swelling in the right heel without any trauma. On physical examination and radiologic assessment, a lesion with calcification and peripheral sclerosis was detected in the medullary cavity of the calcaneus, and computed tomographic images revealed cortical thinning adjacent to the lesion. Magnetic resonance images showed a 23 * 19-mm lesion. Tru-Cut biopsy, performed to clarify the diagnosis, revealed an enchondroma. As a definitive treatment, curettage of the lesion and grafting of the cavity was performed. Although enchondromas are common pathologic abnormalities of the skeleton and are usually asymptomatic, atypical localization, such as the calcaneus, and atypical clinical manifestations, such as heel pain, should also be kept in mind. PMID- 26146975 TI - Infection Prevention and Control in the Podiatric Medical Setting. Challenges to Providing Consistently Safe Care. AB - Unsafe practices are an underestimated contributor to the disease burden of bloodborne viruses. Outbreaks associated with failures in basic infection prevention have been identified in nonhospital settings with increased frequency in the United States during the past 15 years, representing an alarming trend and indicating that the challenge of providing consistently safe care is not always met. As has been the case with most medical specialties, public health investigations by state and local health departments, and the Centers for Disease Control and Prevention, have identified some instances of unsafe practices that have placed podiatric medical patients at risk for viral, bacterial, and fungal infections. All health-care providers, including podiatric physicians, must make infection prevention a priority in any setting in which care is delivered. PMID- 26146977 TI - APMA House of Delegates: Acceptance Address. PMID- 26146983 TI - Academic and social achievement goals: Their additive, interactive, and specialized effects on school functioning. AB - BACKGROUND: Students' pursuit of academic and social goals has implications for school functioning. However, studies on academic and social achievement goals have been relatively independent and mainly conducted with students in culturally Western settings. AIMS: Guided by multiple-goal perspectives, this study examined the role of academic and social achievement goals in outcome variables relevant to academic (achievement, effort/persistence), social (peer relationship satisfaction, loneliness), and socio-academic (cooperative learning, competitive learning, socially regulated, and self-regulated learning) functioning. SAMPLE: A total of 356 Indonesian high-school students (mean age = 16 years; 36% girls) participated in the study. METHODS: A self-report survey comprising items drawn from pre-existing instruments was administered to measure distinct dimensions of achievement goals and outcomes under focus. Regression analysis was performed to examine additive, interactive, and specialized effects of achievement goals on outcomes. RESULTS: Aligned with the hierarchical model of goal relationships (Wentzel, 2000, Contemp. Educ. Psychol., 25, 105), academic and social achievement goals bore additive effects on most outcomes. Findings also revealed a specialized effect on academic achievement and notable interactive effects on cooperative learning. In general, mastery-approach and performance-approach goals were more adaptive than their avoidance counterparts. The effects of social development goals were positive, whereas those of social demonstration-approach goals were mixed. Contrary to prior findings, social demonstration-avoidance goals did not appear to be inimical for school functioning. CONCLUSIONS: Findings underscore the importance of both academic and social achievement goals in day-to day school functioning and the need to consider the meaning of goals and the coordination of multiple goals from cultural lenses. PMID- 26146982 TI - The Perceived Value of Passive Animal Health Surveillance: The Case of Highly Pathogenic Avian Influenza in Vietnam. AB - Economic evaluations are critical for the assessment of the efficiency and sustainability of animal health surveillance systems and the improvement of their efficiency. Methods identifying and quantifying costs and benefits incurred by public and private actors of passive surveillance systems (i.e. actors of veterinary authorities and private actors who may report clinical signs) are needed. This study presents the evaluation of perceived costs and benefits of highly pathogenic avian influenza (HPAI) passive surveillance in Vietnam. Surveys based on participatory epidemiology methods were conducted in three provinces in Vietnam to collect data on costs and benefits resulting from the reporting of HPAI suspicions to veterinary authorities. A quantitative tool based on stated preference methods and participatory techniques was developed and applied to assess the non-monetary costs and benefits. The study showed that poultry farmers are facing several options regarding the management of HPAI suspicions, besides reporting the following: treatment, sale or destruction of animals. The option of reporting was associated with uncertain outcome and transaction costs. Besides, actors anticipated the release of health information to cause a drop of markets prices. This cost was relevant at all levels, including farmers, veterinary authorities and private actors of the upstream sector (feed, chicks and medicine supply). One benefit associated with passive surveillance was the intervention of public services to clean farms and the environment to limit the disease spread. Private actors of the poultry sector valued information on HPAI suspicions (perceived as a non-monetary benefit) which was mainly obtained from other private actors and media. PMID- 26146984 TI - Thermo-responsive hydrogels with N-isopropylacrylamide/acrylamide interpenetrating networks for controlled drug release. AB - Series of thermo-sensitive hydrogels (PNAs) based on N isopropylacrylamide/acrylamide interpenetrating polymer networks were synthesized via in situ free-radical polymerization. Poly (ethylene glycol diacrylate) and poly (epsilon-caprolactone diacrylate) were synthesized as macro-cross-linkers due to their excellent biocompatibilities. The macro-cross-linkers and hydrogels were characterized by (1)H NMR and FT-IR, respectively. The interior morphology of the hydrogels was observed by scanning electron microscopy. The swelling ratios at different temperatures and the swelling/deswelling kinetics of the hydrogels were studied. Their volume phase transition temperatures were also measured by differential scanning calorimetry characterization. The results indicated that the PNA hydrogels had uniform macroporous structures, and they not only had considerable swelling ratios, but also exhibited rapid swelling/deswelling kinetics and response sensitivities. In addition, the weight ratio of AAm/NIPAAm also affected the swelling performance and phase transition temperature of hydrogels, and its value less than 5% was the optimal proportion to achieve excellent comprehensive properties. Levofloxacin lactate and Naproxen were selected as drugs and simulated in vitro condition release, and the drug release results showed that the PNA hydrogels behaved fast release performance. PMID- 26146985 TI - Dysregulation of the NLRP3 inflammasome complex and related cytokines in patients with multiple myeloma. AB - OBJECTIVE: The NLRP3 inflammasome complex, an important regulatory factor of inflammation and cell apoptosis, has attracted considerable attention in the development of tumor. Here, we analyzed the expression and clinical significance of NLRP3 inflammasome complex and related cytokines in patients with multiple myeloma (MM). METHODS: Peripheral blood and bone marrow of 38 newly diagnosed myeloma patients and 25 age- and gender-matched healthy people were studied. NLRP3 and caspase-1 were analyzed using quantitative real-time polymerase chain reaction and Western blot and IL-1beta, IL-18, RANKL, and OPG were evaluated by enzyme-linked immunosorbent assay. RESULTS: We showed that aberrant NLRP3 and caspase-1 expression were observed in MM and down-regulated compared with the healthy people. We further demonstrated that NLRP3 mRNA was negatively correlated with beta2-microglobulin and plasma cell percentage in MM. The downstream cytokines IL-18 and sRANKL/OPG in MM patients were higher than that in control group. Moreover, the lower mRNA levels of NLRP3 and caspase-1 were shown to be positively correlated with IL-1beta in newly diagnosed MM patients. CONCLUSIONS: This study demonstrated that dysregulated expression of NLRP3-caspase-1-IL-1beta axis was observed in patients with MM, suggesting they might be involved in the pathogenesis of MM. PMID- 26146986 TI - Improving left spatial neglect through music scale playing. AB - The study assessed whether the auditory reference provided by a music scale could improve spatial exploration of a standard musical instrument keyboard in right brain-damaged patients with left spatial neglect. As performing music scales involves the production of predictable successive pitches, the expectation of the subsequent note may facilitate patients to explore a larger extension of space in the left affected side, during the production of music scales from right to left. Eleven right-brain-damaged stroke patients with left spatial neglect, 12 patients without neglect, and 12 age-matched healthy participants played descending scales on a music keyboard. In a counterbalanced design, the participants' exploratory performance was assessed while producing scales in three feedback conditions: With congruent sound, no-sound, or random sound feedback provided by the keyboard. The number of keys played and the timing of key press were recorded. Spatial exploration by patients with left neglect was superior with congruent sound feedback, compared to both Silence and Random sound conditions. Both the congruent and incongruent sound conditions were associated with a greater deceleration in all groups. The frame provided by the music scale improves exploration of the left side of space, contralateral to the right hemisphere, damaged in patients with left neglect. Performing a scale with congruent sounds may trigger at some extent preserved auditory and spatial multisensory representations of successive sounds, thus influencing the time course of space scanning, and ultimately resulting in a more extensive spatial exploration. These findings offer new perspectives also for the rehabilitation of the disorder. PMID- 26146987 TI - Physiological Evaluation of Alkali-Salt Tolerance of Thirty Switchgrass (Panicum virgatum) Lines. AB - Soil salt-alkalization is a major limiting factor for crop production in many regions. Switchgrass (Panicum virgatum L.) is a warm-season C4 perennial rhizomatous bunchgrass and a target lignocellulosic biofuel species. The objective of this study was to evaluate relative alkali-salt tolerance among 30 switchgrass lines. Tillers of each switchgrass line were transplanted into pots filled with fine sand. Two months after transplanting, plants at E5 developmental stage were grown in either half strength Hoagland's nutrient solution with 0 mM Na+ (control) or half strength Hoagland's nutrient solution with 150 mM Na+ and pH of 9.5 (alkali-salt stress treatment) for 20 d. Alkali-salt stress damaged cell membranes [higher electrolyte leakage (EL)], reduced leaf relative water content (RWC), net photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (Tr). An alkali-salt stress tolerance trait index (ASTTI) for each parameter was calculated based on the ratio of the value under alkali-salt stress and the value under non-stress conditions for each parameter of each line. Relative alkali-salt tolerance was determined based on principal components analysis and cluster analysis of the physiological parameters and their ASTTI values. Significant differences in alkali-salt stress tolerance were found among the 30 lines. Lowland lines TEM-SEC, Alamo, TEM-SLC and Kanlow were classified as alkali-salt tolerant. In contrast, three lowland lines (AM-314/MS-155, BN-13645 64) and two upland lines (Caddo and Blackwell-1) were classified as alkali-salt sensitive. The results suggest wide variations exist in alkali-salt stress tolerance among the 30 switchgrass lines. The approach of using a combination of principal components and cluster analysis of the physiological parameters and related ASTTI is feasible for evaluating alkali-salt tolerance in switchgrass. PMID- 26146989 TI - Cattle Management for Dairying in Scandinavia's Earliest Neolithic. AB - New evidence for cattle husbandry practices during the earliest period of the southern Scandinavian Neolithic indicates multiple birth seasons and dairying from its start. Sequential sampling of tooth enamel carbonate carbon and oxygen isotope ratio analyses and strontium isotopic provenancing indicate more than one season of birth in locally reared cattle at the earliest Neolithic Funnel Beaker (EN I TRB, 3950-3500 cal. B.C.) site of Almhov in Scania, Sweden. The main purpose for which cattle are manipulated to give birth in more than one season is to prolong lactation for the production of milk and dairy-based products. As this is a difficult, intensive, and time-consuming strategy, these data demonstrate complex farming practices by early Neolithic farmers. This result offers strong support for immigration-based explanations of agricultural origins in southern Scandinavia on the grounds that such a specialised skill set cannot represent the piecemeal incorporation of agricultural techniques into an existing hunter gatherer-fisher economy. PMID- 26146988 TI - CDK5 Regulates Paclitaxel Sensitivity in Ovarian Cancer Cells by Modulating AKT Activation, p21Cip1- and p27Kip1-Mediated G1 Cell Cycle Arrest and Apoptosis. AB - Cyclin-dependent kinase 5 (CDK5) is a cytoplasmic serine/ threonine kinase. Knockdown of CDK5 enhances paclitaxel sensitivity in human ovarian cancer cells. This study explores the mechanisms by which CDK5 regulates paclitaxel sensitivity in human ovarian cancers. Multiple ovarian cancer cell lines and xenografts were treated with CDK5 small interfering RNA (siRNA) with or without paclitaxel to examine the effect on cancer cell viability, cell cycle arrest and tumor growth. CDK5 protein was measured by immunohistochemical staining of an ovarian cancer tissue microarray to correlate CDK5 expression with overall patient survival. Knockdown of CDK5 with siRNAs inhibits activation of AKT which significantly correlates with decreased cell growth and enhanced paclitaxel sensitivity in ovarian cancer cell lines. In addition, CDK5 knockdown alone and in combination with paclitaxel induced G1 cell cycle arrest and caspase 3 dependent apoptotic cell death associated with post-translational upregulation and nuclear translocation of TP53 and p27(Kip1) as well as TP53-dependent transcriptional induction of p21(Cip1) in wild type TP53 cancer cells. Treatment of HEYA8 and A2780 wild type TP53 xenografts in nu/nu mice with CDK5 siRNA and paclitaxel produced significantly greater growth inhibition than either treatment alone. Increased expression of CDK5 in human ovarian cancers correlates inversely with overall survival. CDK5 modulates paclitaxel sensitivity by regulating AKT activation, the cell cycle and caspase-dependent apoptosis. CDK5 inhibition can potentiate paclitaxel activity in human ovarian cancer cells. PMID- 26146990 TI - Development and Validation of EST-SSR Markers from the Transcriptome of Adzuki Bean (Vigna angularis). AB - The adzuki bean (Vigna angularis (Ohwi) Ohwi and Ohashi) is an important grain legume of Asia. It is cultivated mainly in China, Japan and Korea. Despite its importance, few genomic resources are available for molecular genetic research of adzuki bean. In this study, we developed EST-SSR markers for the adzuki bean through next-generation sequencing. More than 112 million high-quality cDNA sequence reads were obtained from adzuki bean using Illumina paired-end sequencing technology, and the sequences were de novo assembled into 65,950 unigenes. The average length of the unigenes was 1,213 bp. Among the unigenes, 14,547 sequences contained a unique simple sequence repeat (SSR) and 3,350 sequences contained more than one SSR. A total of 7,947 EST-SSRs were identified as potential molecular markers, with mono-nucleotide A/T repeats (99.0%) as the most abundant motif class, followed by AG/CT (68.4%), AAG/CTT (30.0%), AAAG/CTTT (26.2%), AAAAG/CTTTT (16.1%), and AACGGG/CCCGTT (6.0%). A total of 500 SSR markers were randomly selected for validation, of which 296 markers produced reproducible amplicons with 38 polymorphic markers among the 32 adzuki bean genotypes selected from diverse geographical locations across China. The large number of SSR-containing sequences and EST-SSR markers will be valuable for genetic analysis of the adzuki bean and related Vigna species. PMID- 26146991 TI - Glutamine Reduces the Apoptosis of H9C2 Cells Treated with High-Glucose and Reperfusion through an Oxidation-Related Mechanism. AB - Mitochondrial overproduction of reactive oxygen species (ROS) in diabetic hearts during ischemia/reperfusion injury and the anti-oxidative role of glutamine have been demonstrated. However, in diabetes mellitus the role of glutamine in cardiomyocytes during ischemia/reperfusion injury has not been explored. To examine the effects of glutamine and potential mechanisms, in the present study, rat cardiomyoblast H9C2 cells were exposed to high glucose (33 mM) and hypoxia reoxygenation. Cell viability, apoptosis, intracellular glutamine, and mitochondrial and intracellular glutathione were determined. Moreover, ROS formation, complex I activity, membrane potential and adenosine triphosphate (ATP) content were also investigated. The levels of S-glutathionylated complex I and mitochondrial apoptosis-related proteins, including cytochrome c and caspase 3, were analyzed by western blot. Data indicated that high glucose and hypoxia reoxygenation were associated with a dramatic decline of intercellular glutamine and increase in apoptosis. Glutamine supplementation correlated with a reduction in apoptosis and increase of glutathione and glutathione reduced/oxidized ratio in both cytoplasm and mitochondria, but a reduction of intracellular ROS. Glutamine supplementation was also associated with less S-glutathionylation and increased the activity of complex I, leading to less mitochondrial ROS formation. Furthermore, glutamine supplementation prevented from mitochondrial dysfunction presented as mitochondrial membrane potential and ATP levels and attenuated cytochrome c release into the cytosol and caspase-3 activation. We conclude that apoptosis induced by high glucose and hypoxia-reoxygenation was reduced by glutamine supplementation, via decreased oxidative stress and inactivation of the intrinsic apoptotic pathway. PMID- 26146992 TI - Lifetime Prevalence and Factors Associated with Head Injury among Older People in Low and Middle Income Countries: A 10/66 Study. AB - INTRODUCTION: Traumatic brain injury (TBI) is a growing public health problem around the world, yet there is little information on the prevalence of head injury in low and middle income countries (LMICs). We utilised data collected by the 10/66 research group to investigate the lifetime prevalence of head injury in defined sites in low and middle income countries, its risk factors and its relationship with disability. METHODS: We analysed data from one-phase cross sectional surveys of all residents aged 65 years and older (n = 16430) distributed across twelve sites in eight low and middle income countries (China, Cuba, Dominican Republic, India, Venezuela, Mexico, Peru, and Puerto Rico). Self reported cases of head injury with loss of consciousness were identified during the interview. A sensitivity analysis including data provided by informants of people with dementia was also used to estimate the impact of this information on the estimates. Prevalence ratios (PR) from Poisson regressions were used to identify associated risk factors. RESULTS: The standardised lifetime prevalence of TBI ranged from 0.3% in China to 14.6% in rural Mexico and Venezuela. Being male (PR: 1.6, 95% CI: 1.29-1.82), younger (PR: 0.95, 95% CI: 0.92-0.99), with lower education (PR 0.91, 95% CI: 0.86-0.96), and having fewer assets (PR 0.92, 95% CI: 0.88-0.96), was associated with a higher prevalence of TBI when pooling estimates across sites. DISCUSSION: Our analysis revealed that the prevalence of TBI in LMICs is similar to that of developed nations. Considering the growing impact of TBI on health resources in these countries, there is an urgent need for further research. PMID- 26146993 TI - Reconfiguration of the Brain Functional Network Associated with Visual Task Demands. AB - Neuroimaging studies have demonstrated that the topological properties of resting state brain functional networks are modulated through task performances. However, the reconfiguration of functional networks associated with distinct degrees of task demands is not well understood. In the present study, we acquired fMRI data from 18 healthy adult volunteers during resting-state (RS) and two visual tasks (i.e., visual stimulus watching, VSW; and visual stimulus decision, VSD). Subsequently, we constructed the functional brain networks associated with these three conditions and analyzed the changes in the topological properties (e.g., network efficiency, wiring-cost, modularity, and robustness) among them. Although the small-world attributes were preserved qualitatively across the functional networks of the three conditions, changes in the topological properties were also observed. Compared with the resting-state, the functional networks associated with the visual tasks exhibited significantly increased network efficiency and wiring-cost, but decreased modularity and network robustness. The changes in the task-related topological properties were modulated according to the task complexity (i.e., from RS to VSW and VSD). Moreover, at the regional level, we observed that the increased nodal efficiencies in the visual and working memory regions were positively associated with the increase in task complexity. Together, these results suggest that the increased efficiency of the functional brain network and higher wiring-cost were observed to afford the demands of visual tasks. These observations provide further insights into the mechanisms underlying the reconfiguration of the brain network during task performance. PMID- 26146994 TI - Molecular, Biochemical and Ultrastructural Changes Induced by Pb Toxicity in Seedlings of Theobroma cacao L. AB - Pb is a metal which is highly toxic to plants and animals, including humans. High concentrations of Pb have been observed in beans of T. cacao, as well as in its products. In this work, we evaluated the molecular, biochemical, and ultrastructural alterations in mature leaves and primary roots of seedlings of two progenies of T. cacao, obtained from seed germination in different concentrations of Pb (0, 0.05, 0.1, 0.2, 0.4, 0.8 g L(-1)), in the form of Pb(NO3)2. The progenies resulted from self-fertilization of Catongo and a cross of CCN-10 x SCA-6. The Pb, supplied via seminal, caused alterations in the ultrastructures of the mesophyll cells and in the amount of starch grains in the chloroplasts. The dosage of substances reactive to thiobarbituric acid showed that Pb induced lipid peroxidation. The activity of guaiacol peroxidases and the expression of genes associated to synthetase of phytochelatin, SODcyt and PER increased in response to Pb. In addition, there was alteration in the expression of stress-related proteins. The progeny of CCN-10 x SCA-6 was more tolerant to Pb stress when compared to Catongo, since: (i) it accumulated more Pb in the roots, preventing its translocation to the shoot; (ii) it presented higher activity of peroxidases in the roots, which are enzymes involved in the elimination of excess of reactive oxygen species; and (iii) increased expression of the gene in the phytochelatin biosynthesis route. The results of the proteomic analysis were of paramount importance to differentiate the defense mechanisms used by both progenies of T. cacao. PMID- 26146995 TI - Estimating In Situ Zooplankton Non-Predation Mortality in an Oligo-Mesotrophic Lake from Sediment Trap Data: Caveats and Reality Check. AB - BACKGROUND: Mortality is a main driver in zooplankton population biology but it is poorly constrained in models that describe zooplankton population dynamics, food web interactions and nutrient dynamics. Mortality due to non-predation factors is often ignored even though anecdotal evidence of non-predation mass mortality of zooplankton has been reported repeatedly. One way to estimate non predation mortality rate is to measure the removal rate of carcasses, for which sinking is the primary removal mechanism especially in quiescent shallow water bodies. OBJECTIVES AND RESULTS: We used sediment traps to quantify in situ carcass sinking velocity and non-predation mortality rate on eight consecutive days in 2013 for the cladoceran Bosmina longirostris in the oligo-mesotrophic Lake Stechlin; the outcomes were compared against estimates derived from in vitro carcass sinking velocity measurements and an empirical model correcting in vitro sinking velocity for turbulence resuspension and microbial decomposition of carcasses. Our results show that the latter two approaches produced unrealistically high mortality rates of 0.58-1.04 d(-1), whereas the sediment trap approach, when used properly, yielded a mortality rate estimate of 0.015 d( 1), which is more consistent with concurrent population abundance data and comparable to physiological death rate from the literature. ECOLOGICAL IMPLICATIONS: Zooplankton carcasses may be exposed to water column microbes for days before entering the benthos; therefore, non-predation mortality affects not only zooplankton population dynamics but also microbial and benthic food webs. This would be particularly important for carbon and nitrogen cycles in systems where recurring mid-summer decline of zooplankton population due to non-predation mortality is observed. PMID- 26146996 TI - Predicting Binding Free Energy Change Caused by Point Mutations with Knowledge Modified MM/PBSA Method. AB - A new methodology termed Single Amino Acid Mutation based change in Binding free Energy (SAAMBE) was developed to predict the changes of the binding free energy caused by mutations. The method utilizes 3D structures of the corresponding protein-protein complexes and takes advantage of both approaches: sequence- and structure-based methods. The method has two components: a MM/PBSA-based component, and an additional set of statistical terms delivered from statistical investigation of physico-chemical properties of protein complexes. While the approach is rigid body approach and does not explicitly consider plausible conformational changes caused by the binding, the effect of conformational changes, including changes away from binding interface, on electrostatics are mimicked with amino acid specific dielectric constants. This provides significant improvement of SAAMBE predictions as indicated by better match against experimentally determined binding free energy changes over 1300 mutations in 43 proteins. The final benchmarking resulted in a very good agreement with experimental data (correlation coefficient 0.624) while the algorithm being fast enough to allow for large-scale calculations (the average time is less than a minute per mutation). PMID- 26146997 TI - The Oral Bacterial Communities of Children with Well-Controlled HIV Infection and without HIV Infection. AB - The oral microbial community (microbiota) plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi's sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section of patients undergoing routine dental care. Multiple specimens from different sampling sites in the mouth were collected for each patient. The goal of the study was to observe the potential diversity of the oral microbiota among individual patients, sample locations, HIV status and various dental characteristics. We found that there were significant differences in the microbiome among the enrolled patients, and between sampling locations. The analysis was complicated by uneven enrollment in the patient cohorts, with only five HIV-negative patients enrolled in the study and by the rapid improvement in the health of HIV-infected children between the time the study was conceived and completed. The generally good oral health of the HIV-negative patients limited the number of dental plaque samples that could be collected. We did not identify significant differences between well-controlled HIV-positive patients and HIV-negative controls, suggesting that well-controlled HIV-positive patients essentially harbor similar oral flora compared to patients without HIV. Nor were significant differences in the oral microbiota identified between different teeth or with different dental characteristics. Additional studies are needed to better characterize the oral microbiome in children and those with poorly-controlled HIV infections. PMID- 26146998 TI - A Common Polymorphism of the Human Cardiac Sodium Channel Alpha Subunit (SCN5A) Gene Is Associated with Sudden Cardiac Death in Chronic Ischemic Heart Disease. AB - Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio = 1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association. PMID- 26146999 TI - A Rapid and Low-Cost PCR Thermal Cycler for Low Resource Settings. AB - BACKGROUND: Many modern molecular diagnostic assays targeting nucleic acids are typically confined to developed countries or to the national reference laboratories of developing-world countries. The ability to make technologies for the rapid diagnosis of infectious diseases broadly available in a portable, low cost format would mark a revolutionary step forward in global health. Many molecular assays are also developed based on polymerase chain reactions (PCR), which require thermal cyclers that are relatively heavy (>20 pounds) and need continuous electrical power. The temperature ramping speed of most economical thermal cyclers are relatively slow (2 to 3 degrees C/s) so a polymerase chain reaction can take 1 to 2 hours. Most of all, these thermal cyclers are still too expensive ($2k to $4k) for low-resource setting uses. METHODOLOGY/PRINCIPAL FINDINGS: In this article, we demonstrate the development of a low-cost and rapid water bath based thermal cycler that does not require active temperature control or continuous power supply during PCR. This unit costs $130 to build using commercial off-the-shelf items. The use of two or three vacuum-insulated stainless-steel Thermos food jars containing heated water (for denaturation and annealing/extension steps) and a layer of oil on top of the water allow for significantly stabilized temperatures for PCR to take place. Using an Arduino based microcontroller, we automate the "archaic" method of hand-transferring PCR tubes between water baths. CONCLUSIONS/SIGNIFICANCE: We demonstrate that this innovative unit can deliver high speed PCR (17 s per PCR cycle) with the potential to go beyond the 1,522 bp long amplicons tested in this study and can amplify from templates down to at least 20 copies per reaction. The unit also accepts regular PCR tubes and glass capillary tubes. The PCR efficiency of our thermal cycler is not different from other commercial thermal cyclers. When combined with a rapid nucleic acid detection approach, the thermos thermal cycler (TTC) can enable on-site molecular diagnostics in low-resource settings. PMID- 26147000 TI - Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study. AB - OBJECTIVES: To explore the pathogenesis of rheumatoid arthritis (RA), the different metabolites were screened in synovial fluid by metabolomics. METHODS: Synovial fluid from 25 RA patients and 10 normal subjects were analyzed by GC/TOF MS analysis so as to give a broad overview of synovial fluid metabolites. The metabolic profiles of RA patients and normal subjects were compared using multivariate statistical analysis. Different proteins were verified by qPCR and western blot. Different metabolites were verified by colorimetric assay kit in 25 inactive RA patients, 25 active RA patients and 20 normal subjects. The influence of hypoxia-inducible factor (HIF)-1alpha pathway on catabolism was detected by HIF-1alpha knockdown. RESULTS: A subset of 58 metabolites was identified, in which the concentrations of 7 metabolites related to energy metabolism were significantly different as shown by importance in the projection (VIP) (VIP >= 1) and Student's t-test (p<0.05). In the 7 metabolites, the concentration of glucose was decreased, and the concentration of lactic acid was increased in the synovial fluid of RA patients than normal subjects verified by colorimetric assay Kit. Receiver operator characteristic (ROC) analysis shows that the concentration of glucose and lactic acid in synovial fluid could be used as dependable biomarkers for the diagnosis of active RA, provided an AUC of 0.906 and 0.922. Sensitivity and specificity, which were determined by cut-off points, reached 84% and 96% in sensitivity and 95% and 85% in specificity, respectively. The verification of different proteins identified in our previous proteomic study shows that the enzymes of anaerobic catabolism were up-regulated (PFKP and LDHA), and the enzymes of aerobic oxidation and fatty acid oxidation were down-regulated (CS, DLST, PGD, ACSL4, ACADVL and HADHA) in RA patients. The expression of HIF-1alpha and the enzymes of aerobic oxidation and fatty acid oxidation were decreased and the enzymes of anaerobic catabolism were increased in FLS cells after HIF-1alpha knockdown. CONCLUSION: It was found that enhanced anaerobic catabolism and reduced aerobic oxidation regulated by HIF pathway are newly recognized factors contributing to the progression of RA, and low glucose and high lactic acid concentration in synovial fluid may be the potential biomarker of RA. PMID- 26147001 TI - A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice. AB - It is well documented that serotonin (5-HT) plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS), which is often provoked by infection, is a disabling illness with an unknown aetiology and diagnosis is based on symptom-specific criteria. However, 5-HT2A receptor expression and peripheral cytokines are known to be upregulated in ME. We sought to examine the relationship between the 5-HT system and cytokine expression following systemic bacterial endotoxin challenge (LPS, 0.5 mg/kg i.p.), at a time when the acute sickness behaviours have largely resolved. At 24 hours post injection mice exhibit no overt changes in locomotor behaviour, but do show increased immobility in a forced swim test, as well as decreased sucrose preference and reduced marble burying activity, indicating a depressive-like state. While peripheral IDO activity was increased after LPS challenge, central activity levels remained stable and there was no change in total brain 5-HT levels or 5-HIAA/5-HT. However, within the brain, levels of TNF and 5-HT2A receptor mRNA within various regions increased significantly. This increase in receptor expression is reflected by an increase in the functional response of the 5-HT2A receptor to agonist, DOI. These data suggest that regulation of fatigue and depressive-like moods after episodes of systemic inflammation may be regulated by changes in 5-HT receptor expression, rather than by levels of enzyme activity or cytokine expression in the CNS. PMID- 26147003 TI - Decreased [3H]naloxone Binding in the Dentate Gyrus of Cloninger Type 1 Anxiety Prone Alcoholics: A Postmortem Whole-Hemisphere Autoradiography Study. AB - BACKGROUND: The opioid system of the central nervous system plays an essential role in the regulation of the rewarding effects of alcohol. Alcohol affects mu opioid receptor (MOR) function. Enhanced MOR function inhibits the GABAergic inhibition of the nucleus accumbens (Nac), which leads to a release of dopamine in the Nac. Of the few pharmaceutical treatments for alcoholism, the MOR antagonists naltrexone and nalmefene benefit most a subset of alcoholics who are characterized with early onset and impulsivity. Our aim was to investigate possible differences in the binding density of [3H]naloxone, a MOR competitive antagonist, between Cloninger type 1 anxiety-prone and harm-avoidant alcoholics, Cloninger type 2 impulsive and antisocial alcoholics, and healthy controls in brain areas that are essential for reward, learning, impulse-control, and mood regulation. METHODS: We used postmortem whole-hemisphere autoradiography with [3H]naloxone, as a binding ligand. A subsequent autoradiography was performed with [3H]DAMGO, a selective MOR agonist. RESULTS: Cloninger type 1 alcoholics displayed decreased [3H]naloxone binding density in all studied brain areas. This trend reached statistical significance in the dentate gyrus, where type 1 alcoholics' [3H]naloxone binding density was significantly decreased (p = 0.019) when compared to controls. A similar trend of decreased binding in type 1 alcoholics was observed in the [3H]DAMGO study. CONCLUSIONS: Our finding suggest that Cloninger type 1 anxiety-prone alcoholics may have an altered [3H]naloxone binding in brain areas related to reward, impulse-control, mood, and learning. The finding lends support to the idea of Cloninger type 1 anxiety-prone alcoholics responding weaker to the opioidergic pharmaceuticals of the treatment of alcoholism than Cloninger type 2 impulsive alcoholics. PMID- 26147002 TI - 14-3-3 Binding and Sumoylation Concur to the Down-Modulation of beta-catenin Antagonist chibby 1 in Chronic Myeloid Leukemia. AB - The down-modulation of the beta-catenin antagonist Chibby 1 (CBY1) associated with the BCR-ABL1 fusion gene of chronic myeloid leukemia (CML) contributes to the aberrant activation of beta-catenin, particularly in leukemic stem cells (LSC) resistant to tyrosine kinase (TK) inhibitors. It is, at least partly, driven by transcriptional events and gene promoter hyper-methylation. Here we demonstrate that it also arises from reduced protein stability upon binding to 14 3-3sigma adapter protein. CBY1/14-3-3sigma interaction in BCR-ABL1+ cells is mediated by the fusion protein TK and AKT phosphorylation of CBY1 at critical serine 20, and encompasses the 14-3-3sigma binding modes I and II involved in the binding with client proteins. Moreover, it is impaired by c-Jun N-terminal kinase (JNK) phosphorylation of 14-3-3sigma at serine 186, which promotes dissociation of client proteins. The ubiquitin proteasome system UPS participates in reducing stability of CBY1 bound with 14-3-3sigma through enhanced SUMOylation. Our results open new routes towards the research on molecular pathways promoting the proliferative advantage of leukemic hematopoiesis over the normal counterpart. PMID- 26147004 TI - Synergistic Induction of Potential Warburg Effect in Zebrafish Hepatocellular Carcinoma by Co-Transgenic Expression of Myc and xmrk Oncogenes. AB - Previously we have generated inducible liver tumor models by transgenic expression of Myc or xmrk (activated EGFR homolog) oncogenes in zebrafish. To investigate the interaction of the two oncogenes, we crossed the two transgenic lines and observed more severe and faster hepatocarcinogenesis in Myc/xmrk double transgenic zebrafish than either single transgenic fish. RNA-Seq analyses revealed distinct changes in many molecular pathways among the three types of liver tumors. In particular, we found dramatic alteration of cancer metabolism based on the uniquely enriched pathways in the Myc/xmrk tumors. Critical glycolytic genes including hk2, pkm and ldha were significantly up-regulated in Myc/xmrk tumors but not in either single oncogene-induced tumors, suggesting a potential Warburg effect. In RT-qPCR analyses, the specific pkm2 isoformin Warburg effect was found to be highly enriched in the Myc/xmrk tumors but not in Myc or xmrk tumors, consistent with the observations in many human cancers with Warburg effect. Moreover, the splicing factor genes (hnrnpa1, ptbp1a, ptbp1b and sfrs3b) responsible for generating the pkm isoform were also greatly up-regulated in the Myc/xmrk tumors. As Pkm2 isoform is generally inactive and causes incomplete glycolysis to favor anabolism and tumor growth, by treatment with a Pkm2-specific activator, TEPP-46, we further demonstrated that activation of Pkm2 suppressed the growth of oncogenic liver as well as proliferation of liver cells. Collectively, our Myc/xmrk zebrafish model suggests synergetic effect of EGFR and MYC in triggering Warburg effect in the HCC formation and may provide a promising in vivo model for Warburg effect. PMID- 26147005 TI - Maternal Supplementation with Oligofructose (10%) during Pregnancy and Lactation Leads to Increased Pro-Inflammatory Status of the 21-D-Old Offspring. AB - Previously, we showed that oligofructose (10%) supplementation during pregnancy and lactation increased endotoxemia in 21-d-old pups. The present study evaluated the effect of 10% oligofructose diet supplementation during pregnancy and lactation in the presence or absence of hydrogenated vegetable fat on the pro inflammatory status of 21-d-old offspring. On the first day of pregnancy, female Wistar rats were divided into the following groups: control diet (C), control diet supplemented with 10% oligofructose (CF), diet enriched with hydrogenated vegetable fat (T) or diet enriched with hydrogenated vegetable fat supplemented with 10% oligofructose (TF). Diets were maintained during pregnancy and lactation. Serum TNF-alpha (tumor necrosis factor alpha) was assessed using a specific kit. Protein expression was determined by Western Blotting, and the relative mRNA levels were analyzed by RT-PCR (real-time polymerase chain reaction). We observed that 10% oligofructose supplementation during pregnancy and lactation increased offspring's IL-6R (interleukin-6 receptor) mRNA levels in the liver and RET (retroperitoneal white adipose tissue) and decreased ADIPOR2 (adiponectin receptor 2) and ADIPOR1 (adiponectin receptor 1) gene expression in liver and EDL (extensor digital longus)/ SOL (soleus) muscles of CF group. Additionally, TF group presented with increased serum TNF-alpha, protein expression of p-NFkappaBp65 (phosphorylated form of nuclear factor kappa B p65 subunit) in liver and IL-6R mRNA levels in RET. These findings were accompanied by decreased levels of ADIPOR1 mRNA in the EDL and SOL muscles of the TF group. In conclusion, supplementing the dam's diet with 10% of oligofructose during pregnancy and lactation, independent of hydrogenated vegetable fat addition, contributes to the increased pro-inflammatory status of 21-d-old offspring, possibly through the activation of the TLR4 (toll like receptor 4) pathway. PMID- 26147006 TI - Neuropilin 1 expression correlates with the Radio-resistance of human non-small cell lung cancer cells. AB - The purpose of this study was to determine the correlation between over expression of the neuropilin 1 (NRP1) gene and growth, survival, and radio sensitivity of non-small cell lung carcinoma (NSCLC) cells. 3-[4,5 dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium broide (MTT) and colony assays were then performed to determine the effect of NRP1 inhibition on the in vitro growth of NSCLC cells. The Annexin V-Fluorescein Isothiocyanate (FITC) apoptosis detection assay was performed to analyse the effect of NRP1 enhancement on apoptosis of NSCLC cells. Transwell invasion and migration assays were employed to examine the metastatic ability of A549 cells post X-ray irradiation. In addition, Western blot assays were carried out to detect the protein level of VEGFR2, PI3K and NF-kappaB. Finally, to examine the effect of shNRP1 on proliferation and radio-sensitivity in vivo, a subcutaneous tumour formation assay in nude mice was performed. Microvessel density in tumour tissues was assessed by immunohistochemistry. The stable transfected cell line (shNRP1-A549) showed a significant reduction in colony-forming ability and proliferation not only in vitro, but also in vivo. Moreover, shRNA-mediated NRP1 inhibition also significantly enhanced the radio-sensitivity of NSCLC cells both in vitro and in vivo. The over-expression of NRP1 was correlated with growth, survival and radio resistance of NSCLC cells via the VEGF-PI3K- NF-kappaB pathway, and NRP1 may be a molecular therapeutic target for gene therapy or radio-sensitization of NSCLC. PMID- 26147007 TI - Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy. AB - IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-kappaB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-kappaB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals. PMID- 26147009 TI - Risk of liver cirrhosis after tuberculosis. PMID- 26147008 TI - Evaluation of a Novel Screw Position in a Type III Distal Phalanx Fracture Model: An Ex Vivo Study. AB - OBJECTIVE: Mechanical evaluation of a novel screw position used for repair in a type III distal phalanx fracture model and assessment of solar canal penetration (SCP). STUDY DESIGN: Experimental study. SAMPLE POPULATION: Disarticulated equine hooves (n = 24) and 24 isolated distal phalanges. METHODS: Hooves/distal phalanges cut in a sagittal plane were repaired with 1 of 2 different cortical screw placements in lag fashion. In group 1 (conventional screw placement), the screw was inserted halfway between the proximal border of the solar canal (SC) and the subchondral bone surface on a line parallel to the dorsal cortex, whereas in group 2, the screw was inserted more palmar/plantar, where a perpendicular line drawn from the group 1 position reached the palmar/plantar cortex. Construct strength was evaluated by 3-point bending to failure. SCP was assessed by CT imaging and macroscopically. RESULTS: Screws were significantly longer in group 2 and in forelimbs. Group 2 isolated distal phalanges had a significantly more rigid fixation compared with the conventional screw position (maximum point at failure 31%, bending stiffness 41% higher). Lumen reduction of the SC was observed in 13/52 specimens (all from group 2), of which 9 were forelimbs. CONCLUSIONS: More distal screw positioning compared with the conventionally recommended screw position for internal fixation of type III distal phalangeal fractures allows placement of a longer screw and renders a more rigid fracture fixation. The novel screw position, however, carries a higher risk of SCP. PMID- 26147010 TI - Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants. AB - Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins. PMID- 26147012 TI - Children and parents' experiences of cognitive behavioral therapy for dental anxiety--a qualitative study. AB - BACKGROUND: There is a high prevalence of dental anxiety in children and adolescents. Cognitive behavioral therapy is emerging as a treatment option. AIM: The purpose of this study is to explore how children with dental anxiety and their parents experience cognitive behavioral therapy (CBT) in dentistry. DESIGN: We interviewed 12 children and one of their parents and conducted a thematic analysis of the transcribed interviews. RESULTS: Perspective shift emerged as overarching theme in our thematic analysis. This theme consisted of three main themes, which were mastery, safety, and reduced fear. Six subthemes were also identified according to our analyses. Mastery includes two subthemes, gradual exposure and autonomy and control. Subthemes and sources for safety feeling were therapeutic alliance and changed appraisal. The theme reduced fear also consisted of two subthemes; reduced anticipatory anxiety and coping. CONCLUSIONS: The results show that parents and children had positive experiences of CBT and its outcome and were able to benefit from this psychological treatment when dealing with dental anxiety. PMID- 26147011 TI - Glycogen synthase kinase-3 inhibitor AR-A014418 suppresses pancreatic cancer cell growth via inhibition of GSK-3-mediated Notch1 expression. AB - BACKGROUND: Glycogen synthase kinase-3 (GSK-3) can act as either a tumour promoter or suppressor by its inactivation depending on the cell type. There are conflicting reports on the roles of GSK-3 isoforms and their interaction with Notch1 in pancreatic cancer. It was hypothesized that GSK-3alpha stabilized Notch1 in pancreatic cancer cells thereby promoting cellular proliferation. METHODS: The pancreatic cancer cell lines MiaPaCa2, PANC-1 and BxPC-3, were treated with 0-20 MUM of AR-A014418 (AR), a known GSK-3 inhibitor. Cell viability was determined by the MTT assay and Live-Cell Imaging. The levels of Notch pathway members (Notch1, HES-1, survivin and cyclinD1), phosphorylated GSK-3 isoforms, and apoptotic markers were determined by Western blot. Immunoprecipitation was performed to identify the binding of GSK-3 specific isoform to Notch1. RESULTS: AR-A014418 treatment had a significant dose-dependent growth reduction (P < 0.001) in pancreatic cancer cells compared with the control and the cytotoxic effect is as a result of apoptosis. Importantly, a reduction in GSK-3 phosphorylation lead to a reduction in Notch pathway members. Overexpression of active Notch1 in AR-A014418-treated cells resulted in the negation of growth suppression. Immunoprecipitation analysis revealed that GSK 3alpha binds to Notch1. CONCLUSIONS: This study demonstrates for the first time that the growth suppressive effect of AR-A014418 on pancreatic cancer cells is mainly mediated by a reduction in phosphorylation of GSK-3alpha with concomitant Notch1 reduction. GSK-3alpha appears to stabilize Notch1 by binding and may represent a target for therapeutic development. Furthermore, downregulation of GSK-3 and Notch1 may be a viable strategy for possible chemosensitization of pancreatic cancer cells to standard therapeutics. PMID- 26147013 TI - Sebaceous Carcinoma of the Ocular Region: The 2014 Professor Winifred Mao Lecture. AB - Sebaceous carcinoma is a malignancy arising in the periocular region that can lead to blindness and tumor-related metastases. This study is a review of published literature and personal experience. This malignancy can arise from the sebaceous units in the tarsus (meibomian glands), in association with the cilia (Zeis glands), in the brow, and in the caruncle. There is a tendency for diffuse intraepithelial growth (pagetoid spread) that can be clinically invisible. Detection before lymph node metastasis is critical. This malignancy often masquerades as chronic unilateral conjunctivitis or blepharitis, typically in older patients. Management includes a 2-step approach with step 1 focused on eyelid and conjunctival map biopsies to determine the full extent of solid deep tumor and pagetoid spread. After complete review of all biopsies, step 2 is performed using local resection for all deep tumor, cryotherapy to pagetoid disease, and reconstruction. In most cases, the posterior lamella of eyelid is sacrificed with tumor removal, whereas the anterior lamella of the eyelid can be saved. After removal and cryotherapy, immediate reconstruction, using clean instruments, with buccal membrane graft for the posterior lamella and skin flap for the anterior lamella, is developed. For persistent or recurrent pagetoid disease, cryotherapy, topical mitomycin C, or plaque radiotherapy is provided. Exenteration is sometimes necessary. Sebaceous carcinoma, if detected early, can be managed with carefully planned map biopsy to determine tumor extent, followed by local resection, cryotherapy, and eyelid reconstruction. Orbital exenteration is occasionally necessary. PMID- 26147014 TI - Letter to the Editor Regarding Sturge-Weber Syndrome (Encephalotrigeminal Angiomatosis): Recent Advances and Future Challenges. PMID- 26147015 TI - The Rodent Model of Glaucoma and Its Implications. AB - Glaucoma is a group of progressive optic neuropathies, characterized by the degeneration of retinal ganglion cells related to the level of intraocular pressure and other factors. The exact pathogenesis of glaucoma is not known, and current therapeutic options are not sufficient to prevent or recover vision loss in glaucoma patients. Functional, repeatable, and easy-to-use animal models are therefore needed. Because of their inherent advantages, rodent animals, including mice and rats, have been widely developed as models to study various aspects of glaucoma and to evaluate possible novel therapies. However, no single model has been shown to emulate all aspects of glaucoma. In this review, we discuss currently available rodent animal models of glaucoma, their strengths and weaknesses, and the possible implications for current glaucoma research. PMID- 26147016 TI - Predictability of Recalcitrance in Neovascular Age-Related Macular Degeneration With Indocyanine Green Angiography. AB - PURPOSE: This study aimed to evaluate the utility of indocyanine green (ICG) angiography in predicting recalcitrance in neovascular age-related macular degeneration (nAMD). DESIGN: A retrospective case series. METHODS: The charts of treatment-naive subjects with nAMD undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy during a 6-month period were retrospectively reviewed. The study group consisted of subjects with persistent retinal edema on optical coherence tomography (OCT) despite 6 consecutive monthly anti-VEGF injections. The control group was age-matched to the study group and consisted of subjects who demonstrated complete resolution of retinal edema on OCT after 3 or fewer monthly anti-VEGF injections. RESULTS: There were 42 study cases and 42 controls included in the analysis. The baseline visual acuity, central macular thickness on OCT, and choroidal neovascularization (CNV) surface area on ICG angiography were statistically similar between the study and control groups. The CNV surface area on ICG angiography 2 months after starting consecutive monthly anti-VEGF injections increased from a baseline of 1.78 +/- 0.86 to 2.66 +/- 0.92 mm2 in the study group (P = 0.008) and decreased from a baseline of 1.94 +/- 0.97 to 1.12 +/ 0.05 mm2 in the control group (P = 0.04); this change in CNV size on ICG angiography from baseline to 2-month follow-up was statistically significant between the study and control groups (P < 0.0001). CONCLUSIONS: Change in CNV surface area on ICG angiography can predict which subjects with nAMD are likely to have persistent retinal edema on OCT after 6 or more consecutive monthly anti VEGF injections. PMID- 26147017 TI - Isolated Congenital Muscular Diverticulum of the Left Ventricular Apex Complicated with Mural Thrombosis in an Adult. AB - We present a case of apical isolated congenital left ventricular (LV) diverticulum complicated with mural thrombosis in an adult and elucidate the echocardiographic features for differential diagnosis of LV outpouchings. PMID- 26147018 TI - Integrative approach for severe anxiety. PMID- 26147019 TI - Anaphylactic Shock at the End of Hemodialysis. AB - Allergic reactions to epoetin alfa, including anaphylaxis, have been described but desensitization in the setting of an IgE-mediated reaction has not been reported. We present a case of a hemodialysis patient who developed symptoms of an IgE-mediated allergic response to epoetin alfa that occurred after each administration. These reactions progressed to a single episode of anaphylaxis with generalized pruritus, urticaria, oropharyngeal edema, and hypotension that prompted its discontinuation. Intradermal skin testing confirmed an allergic response to this agent. The patient then underwent a desensitization procedure to epoetin alpha after which she was able to tolerate it without further problems. PMID- 26147020 TI - Fronto-Orbital Osteotomy Reshaping for Supraorbital Ridge Protrusion. AB - BACKGROUND: Supraorbital ridge protrusion is an unpleasant facial characteristic in China. Literature describing the surgical correction of supraorbital ridge protrusion is scarce. OBJECTIVE: This study aimed to present a surgical technique for correcting supraorbital ridge protrusions. METHOD: The anterior wall of the frontal sinus and the outer cortex of the frontal bone were removed to form a frontal bone flap, which was regrafted after being trimmed to suitable shape and size. Microabsorbable or titanium plates and screws were fixed on the bilateral side of the bone flap. Anteroposterior depth (the distance between the anterior and posterior wall of the frontal sinus, A-PD), nasofrontal angle, and forehead inclination were measured on the middle sagittal plane before and after corrective operation. RESULT: All patients got satisfactory appearances in this study. All the variations of measurements showed that the excessive prominent supraorbital ridge had been improved significantly. The result of the Wilcoxon signed-rank test showed that the P value for A-PD was 0.043, which indicated that there were significant statistical differences between preoperative and postoperative A-PD in the midsagittal plane. No recurrence or complications were found during 1 year of follow-up. CONCLUSIONS: The fronto-orbital reshaping osteotomy is a reliable technique for correcting supraorbital ridge protrusions. Major complications were not observed and satisfying appearances were obtained. PMID- 26147022 TI - Pterygoid Plate Fractures: Not Limited to Le Fort Fractures. AB - Pterygoid plate fractures are often described in the setting of Le Fort fractures. The goal of this study was to define other craniofacial fracture patterns causing injury to the pterygoid plates. A retrospective review of computed tomography (CT) scans obtained on craniofacial trauma patients over a 5 year period revealed 209 patients with pterygoid plate fractures. Pterygoid plate fractures in 78 patients (37.3%) were unrelated to Le Fort fractures. Common causes included sphenotemporal buttress fractures in 26 patients (33.3%), temporal bone fractures in 18 patients (23.1%), zygomaticomaxillary complex fractures in 17 patients (21.8%), and displaced mandible fractures in 14 patients (17.9%). These findings indicate that approximately one third of pterygoid plate fractures do not result from Le Fort pattern injuries and that the craniofacial surgeon should have a broad differential for causes of pterygoid plate fractures when reviewing trauma imaging. PMID- 26147021 TI - Optimizing Collagen Scaffolds for Bone Engineering: Effects of Cross-linking and Mineral Content on Structural Contraction and Osteogenesis. AB - INTRODUCTION: Osseous defects of the craniofacial skeleton occur frequently in congenital, posttraumatic, and postoncologic deformities. The field of scaffold based bone engineering emerged to address the limitations of using autologous bone for reconstruction of such circumstances. In this work, the authors evaluate 2 modifications of three-dimensional collagen-glycosaminoglycan scaffolds in an effort to optimize structural integrity and osteogenic induction. METHODS: Human mesenchymal stem cells (hMSCs) were cultured in osteogenic media on nonmineralized collagen-glycosaminoglycan (C-GAG) and nanoparticulate mineralized collagen-glycosaminoglycan (MC-GAG) type I scaffolds, in the absence and presence of cross-linking. At 1, 7, and 14 days, mRNA expression was analyzed using quantitative real-time -reverse-transcriptase polymerase chain reaction for osteocalcin (OCN) and bone sialoprotein (BSP). Structural contraction was measured by the ability of the scaffolds to maintain their original dimensions. Mineralization was detected by microcomputed tomographic (micro-CT) imaging at 8 weeks. Statistical analyses were performed with Student t-test. RESULTS: Nanoparticulate mineralization of collagen-glycosaminoglycan scaffolds increased expression of both OCN and BSP. Cross-linking of both C-GAG and MC-GAG resulted in decreased osteogenic gene expression; however, structural contraction was significantly decreased after cross-linking. Human mesenchymal stem cells directed mineralization, detected by micro-CT, was increased in nanoparticulate mineralized scaffolds, although the density of mineralization was decreased in the presence of cross-linking. CONCLUSIONS: Optimization of scaffold material is an essential component of moving toward clinically translatable engineered bone. Our current study demonstrates that the combination of nanoparticulate mineralization and chemical cross-linking of C-GAG scaffolds generates a highly osteogenic and structurally stable scaffold. PMID- 26147024 TI - A True Single-Stage Reconstruction of a Projected Auricle for Concha-Type Microtia Incorporating Endoscopically Harvested Temporoparietal Fascia. AB - Reconstruction of microtia with autogenous costal cartilage that produces a well projected ear in a single stage is a challenging endeavor. In this case report, we describe a single-stage, projected costal cartilage-based reconstruction of concha type mitoria. Due to the patient's low hairline, his hair-bearing scalp would encroach on the ear framework if placed subcutaneously in the standard fashion. Thus, a large TPF flap harvested with endoscopic assistance was planned to achieve both a color-matched hairless skin envelope and a well-projected ear in single stage. PMID- 26147023 TI - Aesthetic Motivation of Geriatric Rhinoplasty The Surgical Outcome. AB - BACKGROUND: Rhinoplasty in the elderly population has recently emerged as an issue in terms of rejuvenation. There, however, is a paucity of published data on geriatric rhinoplasty in Asian patients. The aims of this study were to investigate the motivation of aged Korean patients to undergo the procedure, and to demonstrate our experience of rhinoplasty in patients of 60 years of age and older. METHODS: A total of 20 patients, 11 men and 9 women, underwent rhinoplasty between December 2003 and September 2012 at the Asan Medical Center. Anthropometric measurements were performed preoperatively and postoperatively. Two independent ENT surgeons viewed photographs to assess the surgical outcomes. Patient satisfaction was graded using a visual analogue scale (from 1 = dissatisfied, to 4 = satisfied) by telephone interview. RESULTS: The rhinoplasty performed in our patient cohort aimed to address deviated nose (30%), postinfectious deformed nose (15%), flat nose (15%), saddle nose (10%), and additional cosmetic rhinoplasty for planned septoplasty (10%). Anthropometric measurements showed statistically significant improvements in nasal tip projection, nasal length, dorsal height, and radix height. The mean satisfaction scores were 2.9 for physicians and 2.5 for patients. Three patients (15%) experienced incomplete improvement of nasal obstruction, and 7 patients (35%) expressed aesthetic dissatisfaction about tip shape or dorsal deviation after rhinoplasty. Three patients (15%) underwent revision rhinoplasty. CONCLUSIONS: The aged patients in this study received rhinoplasty to resolve their long cherished desires. If elderly patients have no risk of general condition, surgeons do not need to discourage a patient's wish to improve their appearance. PMID- 26147025 TI - Repair of the Defect of Nasolabial Cyst Using Bioresorbable Plate. PMID- 26147026 TI - Evaluation of Nasal Obstruction in Various Sagittal Skeletal Deformity of Jaws. AB - Nasal obstruction (NO) is a common symptom present in 25% of the general population, which significantly interferes with the quality of life. The different facial profiles and malocclusion patterns could be associated with the degree of NO. In order to evaluate the nasal function in patients with different facial morphology patterns, the authors developed a prospective study in which 88 patients from a dentofacial deformities center were included. These patients were submitted to fibrorhinoscopy (Mashida, ENT PIII) with a 3.2-mm cannula under topical anesthesia to evaluate septal deviation, inferior and medium turbinates, and pharyngeal tonsils. The 88 patients included in the study were divided into 3 groups according to the classification of the facial profile, distributed as follows: 32 class I, 28 class II, and 28 class III; the data collected was statistically analyzed by analysis of variance and the results are shown. The patients included in this study presented similar prevalence of NO with the reduction of airway function efficiency. Although it was not a statistically different, the group II presented higher mean Nasal Obstruction Syndrome Evaluation scores. PMID- 26147028 TI - Evident Proptosis and Diplopia Due to Massive Orbital Ivory Osteoma. PMID- 26147027 TI - A Reliable Method to Measure Lip Height Using Photogrammetry in Unilateral Cleft Lip Patients. AB - There is still no reliable tool to determine the outcome of the repaired unilateral cleft lip (UCL). The aim of this study was therefore to develop an accurate, reliable tool to measure vertical lip height from photographs. The authors measured the vertical height of the cutaneous and vermilion parts of the lip in 72 anterior-posterior view photographs of 17 patients with repairs to a UCL. Points on the lip's white roll and vermillion were marked on both the cleft and the noncleft sides on each image. Two new concepts were tested. First, photographs were standardized using the horizontal (medial to lateral) eye fissure width (EFW) for calibration. Second, the authors tested the interpupillary line (IPL) and the alar base line (ABL) for their reliability as horizontal lines of reference. Measurements were taken by 2 independent researchers, at 2 different time points each. Overall 2304 data points were obtained and analyzed. Results showed that the method was very effective in measuring the height of the lip on the cleft side with the noncleft side. When using the IPL, inter- and intra-rater reliability was 0.99 to 1.0, with the ABL it varied from 0.91 to 0.99 with one exception at 0.84. The IPL was easier to define because in some subjects the overhanging nasal tip obscured the alar base and gave more consistent measurements possibly because the reconstructed alar base was sometimes indistinct. However, measurements from the IPL can only give the percentage difference between the left and right sides of the lip, whereas those from the ABL can also give exact measurements. Patient examples were given that show how the measurements correlate with clinical assessment. The authors propose this method of photogrammetry with the innovative use of the IPL as a reliable horizontal plane and use of the EFW for calibration as a useful and reliable tool to assess the outcome of UCL repair. PMID- 26147030 TI - Second Cancer in a Patient With Breast Cancer. PMID- 26147031 TI - Morphometric Study of Endoscopic Transoccipital Approach to Lateral Ventricle With Magnetic Resonance Imaging. AB - Endoscopic surgery has been applied in the treatment of lateral cerebral ventricular lesions for years, but few morphometric studies in vivo have been reported with medical imaging. In the current study, the authors aimed to investigate the related morphometric data of endoscopic transoccipital approach to lateral ventricle with the magnetic resonance images of lateral ventricle from healthy adults anonymously. Seven parameters on the axial plane and 3 on the left occipital horn of sagittal plane of T1-weighted image were measured and the results were as follows: The distance from incision to the cranium posterior intersection with midsagittal line (D1) was 29.69 +/- 3.09 mm.The distance from incision to the superior border of transverse sinus (D2) was 29.40 +/- 4.76 mm; the length between incision and the entry trajectory intersection K of posterior wall of lateral ventricle (D3) was 43.25 +/- 4.20 mm; the distance between the midpoint of largest width of occipital horn and the intersection K (D4) was 9.39 +/- 2.75 mm; the bilateral occipital horn and left frontal horn (W1, W2, W3) were, respectively: 10.29 +/- 2.27, 9.74 +/- 2.51, and 7.91 +/- 1.19 mm. The angulations between entry trajectory and the projections of longitudinal axis of posterior lateral ventricle body that goes through the midpoint of largest breadths of left occipital horn on the axial and sagittal planes and the longitudinal axis of temporal horn (A1, A2, A3) were separately as follows: (38.10 +/- 4.50) degrees , (30.30 +/- 4.47) degrees , and (31.08 +/- 4.54) degrees . The resultant anatomical data of the distances and angles validate the previous surgical experience and, moreover, facilitate neurosurgery to the lateral ventricle through the endoscopic transoccipital approach. PMID- 26147032 TI - Clinicopathologic Assessment of Myositis Ossificans Circumscripta of the Masseter Muscles. PMID- 26147033 TI - Longitudinal Photogrammetric Analysis of Soft Tissue Facial Changes: A Systematic Review of the Literature and a Summary of Recommendations. AB - Human faces are under a constant state of change throughout the entirety of one's lifetime. Photogrammetry has been advocated for use in large epidemiological studies investigating facial characteristics. This study aimed to review existing longitudinal photogrammetric studies in terms of the measurements selected and the observed facial changes overtime. A comprehensive literature search was performed in 4 databases, PubMed, ISI Web of Science, EMBASE, and Scopus, which was supplemented by hand search. No limitations were set as to the language, dates, or status of publication. The records were assessed for the eligibility and rated for the risk of bias by 2 independent reviewers. Data regarding study characteristics, measurements selected and the outcomes reported, were extracted for analysis. An initial search identified 5127 studies. After 2 rounds of study screening, 6 eligible studies informed this review. The risk of bias of the studies ranged from 41.7% to 80.8%. Only 1 study performed sample size calculation, and only 17% of the studies had a sample size of over 30 subjects. Confidence interval was reported by none of the studies. The facial features assessed varied among the studies, and some studies focused on only specific regions of the face. Photogrammetry has been used by a limited number of studies in the analysis of longitudinal soft tissue facial changes. Moreover, these studies are heterogeneous with respect to their levels of risk of bias and the facial features assessed. Recommendations are provided to improve the qualities of future photogrammetric studies. PMID- 26147034 TI - Basosquamous or Basal Cell Carcinoma? The Importance of the Differential Diagnosis. PMID- 26147035 TI - Intraoperative Computed Tomography Ensures Inferior Alveolar Nerve Safety During Orthognathic Surgery. PMID- 26147036 TI - Myositis Ossificans Circumscripta in the Masseter Muscle Mimicking Phleboliths. PMID- 26147038 TI - A Sign of Le Fort Fracture in Axial Computed Tomography Scan. PMID- 26147037 TI - Severe Obstructive Sleep Apnea Due to Massive Cervical Lipohypertrophy. AB - Obstructive sleep apnea is a difficult problem to deal with. Many studies on the pathogenesis of obstructive sleep apnea were performed in the past, and we present cervical lipohypertrophy causing severe obstructive sleep apnea in this article. PMID- 26147039 TI - A Marking for Moderate Bilateral Cleft Lip. PMID- 26147040 TI - A Useful Instrument to Protect the Surrounding Tissues in Craniofacial Surgery: Sterile Metal Tablespoon. PMID- 26147041 TI - An Incidentally Discovered Nasal Supernumerary Tooth. PMID- 26147042 TI - Awake Nasotracheal Fiberoptic Intubation With Different Conscious Sedation Techniques. PMID- 26147043 TI - An Unusual Deformity of the Nose: Medial Crural Fracture. PMID- 26147044 TI - Frontofacial Monobloc Advancement With Simultaneous Frontal Cranioplasty in Adolescents With Residual Apert Syndrome Deformations. AB - INTRODUCTION: The treatment of faciocraniosynostosis has steadily evolved since the introduction of craniofacial surgery in the 1950s. The aim of this study is to demonstrate the positive results obtained by frontofacial monobloc advancement with simultaneous frontal cranioplasty in adolescents with adult facial bones and residual Apert syndrome deformations. MATERIALS AND METHODS: Three adolescents underwent surgery between September 1, 2010 and March 31, 2011. All had faciocraniosynostosis in the context of Apert syndrome and had undergone brain decompression surgery during the first year of life. However, they presented intracranial hypertension. The authors carried out frontofacial monobloc advancement with internal distraction and frontal cranioplasty. RESULTS: The mean frontal advancement was 13.8 mm. The mean maxillary advancement was 16.3 mm. About exorbitism, 2 patients had grade III and 1 had grade I before surgery. After monobloc advancement, 2 patients had no exorbitism and 1 had grade I. About dental occlusion, 3 patients had class III before surgery and were overcorrected in class II after advancement. DISCUSSION: Frontofacial monobloc advancement yields satisfactory functional and esthetic results in these cases. In conclusion, simultaneous frontofacial monobloc advancement and cranioplasty appears to be a promising technique for the treatment of adolescents with residual craniofacial deformations. PMID- 26147045 TI - Cicatricial pemphigoid vegetans in a Polish woman. PMID- 26147046 TI - Promoting Informed Decision Making for Comparative Effectiveness Randomized Trials. PMID- 26147047 TI - Seeing into the xylem using non-invasive techniques provides clarity in understanding mechanisms involved in long-distance sap transport in plants:. PMID- 26147048 TI - Can We Use the Disposable Laparoscopic Clip Appliers as Suture Anchors? An In Vitro Feasibility Study. AB - INTRODUCTION: Intracorporeal suturing is time-consuming and could be difficult in certain operative circumstances. Instead of knot tying, specially designed clips have been introduced to anchor and secure the end of a single strand or suture. Although these clips provide a maximal required holding grip (HG), they considerably increase the cost of the procedure. The aim of this in vitro study was to identify the feasibility, and means of achieving the best HG, of commonly used disposable automatic clip appliers (LCAs) over regular strands. METHODS: We placed 2-0 PDS (rigid) and 2-0 Vicryl (soft) sutures through fresh gastric wall specimens. Six different commercial-type LCAs, all having large or medium/large clips, were applied at the distal end of each suture. An IMDA manual digital force gauge was used to measure the HG of each clip at 2 positions: the middle clip position and the angle (at the crouch) position. A total of 192 measurements were taken. The results were classified into 3 HG levels measured by Newton units (N): the strongest grip (> 1 N), medium grip (> 0.5 and < 1 N), and weak grip (< 0.5 N). RESULTS: The strongest HG was obtained by applying 10 to 12 mm LCAs with large or medium/large clips over PDS at an angle position (HG = 1.1 +/- 0.2 to 1.6 +/- 0.3 N). The weakest grip was obtained by applying any type of LCA over Vicryl at the middle position (HG = 0.08 +/- 0.04 to 0.2 +/- 0.06 N, P < 0.001). The latter was associated with clips freely falling off the sutures even before applying any force. In general, more force was needed to dislodge any brand clip from the PDS compared with Vicryl suture (0.8 +/- 0.6 vs. 0.4 +/- 0.3 N, P < 0.001). The angle position was always stronger than the middle position (0.9 +/- 0.6 vs. 0.3 +/- 0.2 N, P < 0.001). There was a trend for the 10 to 12 mm LCA to have a better HG than the 5 mm ones (0.65 +/- 0.5 vs. 0.51 +/- 0.5 N, P = 0.08). CONCLUSIONS: We propose that 10 to 12 mm LCAs generate enough HG to secure a single strand when clips are placed at the angle position. This is especially true over PDS (hard) strands. The application of 5 mm LCA clips to secure the end of the Vicryl strand is not recommended. Further clinical studies are warranted. PMID- 26147049 TI - Minimally Invasive Distal Pancreatectomy: A Single-Center Analysis of Outcome With Experience and Systematic Review of the Literature. AB - BACKGROUND: The aim of this study is to analyze the learning curve for laparoscopic distal pancreatectomy (LDP) in our series and review the literature on learning curves for LDP and robotic distal pancreatectomy (RDP). METHODS: Learning curve analysis was performed by split group and cumulative sum (CUSUM) analysis of blood loss, operative time, and length of stay. The systematic review identified studies analyzing changes in outcome with experience. RESULTS: A total of 25 resections were performed. CUSUM analysis of operative time found learning curves of 10 cases for LDP and splenectomy and 11 for LDP with splenic preservation. CUSUM analysis of blood loss showed approximately 6 cases. In the literature, values of 10 cases of LDP and approximately 7 RDP were found. CONCLUSIONS: Low numbers of LDP are required to reach proficiency in the hands of expert laparoscopic surgeons. Our results correspond with numbers quoted in the literature. PMID- 26147052 TI - Recurrent Right-Sided Ptosis in a Child. Recurrent Painful Ophthalmoplegic Neuropathy. PMID- 26147053 TI - Behavioral Epigenetics of Family-Centered Care in the Neonatal Intensive Care Unit. PMID- 26147054 TI - Sequential Intravenous Oral Antibiotic Therapy for Osteomyelitis: How Short Is Long Enough? PMID- 26147056 TI - Error in Abstract. PMID- 26147055 TI - Incorrect Information in Text. PMID- 26147057 TI - Sleep Terrors and Sleepwalking: Common Parasomnias of Childhood. PMID- 26147059 TI - Comparison of US Birth Weight References and the International Fetal and Newborn Growth Consortium for the 21st Century Standard. AB - IMPORTANCE: This study introduces how the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) international birth weight standards alter our previous understanding and interpretations of fetal growth restriction as represented by small for gestational age (SGA) status. OBJECTIVES: To compare the birth weight distributions of the INTERGROWTH-21st international standard to commonly used US references and examine the differences in the prevalence and neonatal mortality risk of SGA status (below the 10th percentile of a population reference). DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from 16 prospective cohorts of newborns on gestational age, birth weight, and systematic mortality follow-up through 28 days from 10 low- and middle-income countries. The studies included were conducted between 1983 and 2008. The analysis was conducted in 2014. Infants were categorized as SGA using the 1991 US birth weight reference, the 1999-2000 US birth weight reference, and the new INTERGROWTH-21st standard. For each study, we compared the SGA prevalence and the risk ratio between SGA status and neonatal mortality, calculated using Poisson regression with robust error variance. MAIN OUTCOMES AND MEASURES: We examine neonatal mortality (death within the first 28 days after birth) as the main outcome measure. RESULTS: The pooled SGA prevalence was 23.7% (95% CI, 16.5% 31.0%) using the INTERGROWTH-21st standard compared with 36.0% (95% CI, 27.0% 45.0%) with the US 2000 reference. The relative decrease in prevalence was larger among infants born at 33 to less than 37 weeks' gestation compared with term infants. The pooled neonatal mortality risk did not differ significantly; the adjusted risk ratios were 2.13 (95% CI, 1.78-2.54; P < .001) for the INTERGROWTH 21st standard and 2.12 (95% CI, 1.81-2.48; P < .001) for the US 2000 reference. CONCLUSIONS AND RELEVANCE: To our knowledge, INTERGROWTH-21st is the first international newborn standard for size for gestational age for healthy fetal growth. We observed a greater-than-one-quarter reduction in SGA prevalence and no significant change in the associated neonatal mortality risk, resulting in a decrease in the percentage of neonatal death attributable to SGA. Our study sheds light on how previously published studies on SGA status may be reinterpreted with the introduction of this new birth weight standard. PMID- 26147060 TI - Self-reported student confidence in troubleshooting ability increases after completion of an inquiry-based PCR practical. AB - Inquiry-based learning (IBL) activities are complementary to the processes of laboratory discovery, as both are focused on producing new findings through research and inquiry. Here, we describe the results of student surveys taken pre- and postpractical to an IBL undergraduate practical on PCR. Our analysis focuses primarily student perceptions of knowledge acquisition and their ability to troubleshoot problems. The survey results demonstrate significant self-reported gains in knowledge related to DNA structure and PCR, and an increase in confidence with "troubleshooting problems during scientific experiments." We conclude that the IBL-based approach that combines PCR primer design with wet laboratory experimentation using student-designed primers, provides students a sense of confidence by imparting workplace and research skills that are integral to diverse forms and applications of laboratory practices. PMID- 26147062 TI - Increased urine podocyte-associated messenger RNAs in severe obesity are evidence of podocyte injury. AB - OBJECTIVE: The aim of this study was to correlate different degrees of excess weight with the expression of podocyte-associated messenger RNAs (mRNAs) in urine. METHODS: The sample comprised 83 patients with overweight or obesity class I, II, or III and 18 healthy controls. The expression of nephrin, podocin, podocalyxin, alpha-actinin-4, alpha3beta1integrin, vascular endothelial growth factor, and transforming growth factor-beta (TGF-beta1 ) mRNA in urine was quantified with the real-time polymerase chain reaction. mRNA expression was correlated with body mass index, the metabolic syndrome, albuminuria, and inflammation. RESULTS: Adults with obesity class III had higher levels of serum lipids, glucose, HbA1C, insulin resistance, and C-reactive protein (P < 0.05), with 85% of the subjects meeting criteria for the metabolic syndrome (P < 0.001 vs. other groups). Urinary podocyte-associated mRNAs were higher in adults with obesity class III than in other groups (P < 0.05). Patients with overweight or obesity class I or II also had higher levels of podocyte mRNAs than controls: nephrin (P = 0.021), alpha-actinin-4 (P = 0.014), alpha3beta1integrin (P = 0.036), and TGF-beta1 (P = 0.005). Metabolic syndrome, hyperinsulinemia, and C reactive protein were correlated with podocyturia, but only higher insulin levels were related regardless of obesity. CONCLUSIONS: Severe obesity and hyperinsulinemia were associated with higher urinary expression of podocyte associated mRNAs, even at normal urinary albumin excretion rates. PMID- 26147061 TI - Temporal dynamics of inflammatory cytokines/chemokines during sofosbuvir and ribavirin therapy for genotype 2 and 3 hepatitis C infection. AB - The analysis of inflammatory cytokines and chemokines produced during hepatitis C virus (HCV) infection has advanced our understanding of viral-host interactions and identified predictors of treatment response. Administration of interferons (IFNs) made it difficult to interpret biomarkers of immune activation during treatment. Direct-acting antiviral (DAA) regimens without IFN are now being used to treat HCV with excellent efficacy. To gain insight into HCV-host interactions occurring before, during, and after HCV treatment, we performed a case-control study that measured serial plasma levels of IFN-gamma-inducible protein 10 (IP 10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1 beta (MIP-1beta), and interleukin-18 (IL-18) in 131 patients with chronic HCV treated with sofosbuvir (SOF) plus ribavirin (RBV). A linear regression analysis using baseline factors identified strong positive associations between elevated alanine aminotransferase and pretreatment IP-10 and between the presence of cirrhosis and elevated pretreatment IL-18. Mean IP-10, MCP-1, MIP-1beta, and IL 18 levels all decline on therapy, but display different dynamics late in treatment and after cessation of therapy. On treatment, IP-10 and MIP-1beta levels were significantly higher in individuals who achieved sustained virological response (SVR). Logistic regression analyses examining treatment response in all patients demonstrated significant associations between higher baseline MIP-1beta levels and smaller decreases in MIP-1beta early in treatment and SVR. Higher early MIP-1beta levels were also significantly associated with SVR in subsets of patients with cirrhosis and individuals with genotype 3 (GT3) infection, two factors associated with decreased responsiveness to treatment. CONCLUSION: Changes in IP-10 levels mirror HCV RNA, suggesting that IP-10 is an indicator of innate immune viral recognition. MIP-1beta levels remain elevated in GT2/3 patients who achieved SVR, suggesting differential immune activation in those who respond to SOF/RBV therapy and a potential role in predicting treatment responses. PMID- 26147063 TI - Size-balanced community reorganization in response to nutrients and warming. AB - It is widely accepted that global warming will adversely affect ecological communities. As ecosystems are simultaneously exposed to other anthropogenic influences, it is important to address the effects of climate change in the context of many stressors. Nutrient enrichment might offset some of the energy demands that warming can exert on organisms by stimulating growth at the base of the food web. It is important to know whether indirect effects of warming will be as ecologically significant as direct physiological effects. Declining body size is increasingly viewed as a universal response to warming, with the potential to alter trophic interactions. To address these issues, we used an outdoor array of marine mesocosms to examine the impacts of warming, nutrient enrichment and altered top-predator body size on a community comprised of the predator (shore crab Carcinus maenas), various grazing detritivores (amphipods) and algal resources. Warming increased mortality rates of crabs, but had no effect on their moulting rates. Nutrient enrichment and warming had near diametrically opposed effects on the assemblage, confirming that the ecological effects of these two stressors can cancel each other out. This suggests that nutrient-enriched systems might act as an energy refuge to populations of species under metabolic constraints due to warming. While there was a strong difference in assemblages between mesocosms containing crabs compared to mesocosms without crabs, decreasing crab size had no detectable effect on the amphipod or algal assemblages. This suggests that in allometrically balanced communities, the expected long-term effect of warming (declining body size) is not of similar ecological consequence to the direct physiological effects of warming, at least not over the six week duration of the experiment described here. More research is needed to determine the long-term effects of declining body size on the bioenergetic balance of natural communities. PMID- 26147058 TI - Anthropometric Characterization of Impaired Fetal Growth: Risk Factors for and Prognosis of Newborns With Stunting or Wasting. AB - IMPORTANCE: Stunting (short length for age) and wasting (low body mass index [BMI] for age) are widely used to assess child nutrition. In contrast, newborns tend to be assessed solely based on their weight. OBJECTIVE: To use recent international standards for newborn size by gestational age to assess how stunted and wasted newborns differ in terms of risk factors and prognoses. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study with follow-up until hospital discharge was conducted at urban sites in Brazil, China, India, Italy, Kenya, Oman, England, and the United States that are participating in the INTERGROWTH 21st Project. The study was conducted from April 27, 2009, to March 2, 2014, and the final dataset for analyses was locked on March 19, 2014. EXPOSURES: Sociodemographic and behavioral maternal risk factors, previous pregnancy history, and maternal and fetal conditions during pregnancy were investigated as risk factors for stunting and wasting. Anthropometry at birth was used to predict for neonatal prognosis. MAIN OUTCOMES AND MEASURES: Newborn stunting and wasting were defined as birth length and BMI for gestational age below the third centiles of the INTERGROWTH-21st standards. Prognosis was assessed through mortality before hospital discharge, admission to neonatal intensive care units, and newborn complications. RESULTS: From the 60 206 singleton live births during the study period, we selected all newborns between 33 weeks' and 42 weeks 6 days' gestation at birth (51 200 [85%]) with reliable ultrasound dating. Stunting affected 3.8% and wasting 3.4% of all newborns; both conditions were present in 0.7% of the sample. Of the 26 conditions studied, five were more strongly associated with stunting than with wasting (reported as odds ratios [OR]; 95% CI): short maternal height (6.7; 5.1-9.0), younger maternal age (0.7; 0.5-0.9), smoking (2.8; 2.3-3.3), illicit drug use (2.3; 1.5-3.6), and clinically suspected intrauterine growth restriction (5.2; 4.5-6.0). Wasting was more strongly related than stunting with 4 newborn outcomes (neonatal intensive care stay, 6.7 [5.5 8.1]; respiratory distress syndrome, 4.0 [3.3-4.9]; transient tachypnea, 2.1 [1.5 2.9]; and no oral feeding for >24 hours, 5.0 [3.9-6.5]). Maternal gestational diabetes mellitus was protective against wasting (0.6; 0.5-0.8) but not against stunting (0.9; 0.7-1.1). CONCLUSIONS AND RELEVANCE: Although newborn stunting and wasting share some common determinants, they are distinct phenotypes with their own risk factors and neonatal prognoses. To be consistent with the literature on infant and child nutrition, newborns should be classified using the 2 phenotypes of stunting and wasting. The distinction will help to prioritize preventive interventions and focus the management of fetal undernutrition. PMID- 26147064 TI - A purification process for heparin and precursor polysaccharides using the pH responsive behavior of chitosan. AB - The contamination crisis of 2008 has brought to light several risks associated with use of animal tissue derived heparin. Because the total chemical synthesis of heparin is not feasible, a bioengineered approach has been proposed, relying on recombinant enzymes derived from the heparin/HS biosynthetic pathway and Escherichia coli K5 capsular polysaccharide. Intensive process engineering efforts are required to achieve a cost-competitive process for bioengineered heparin compared to commercially available porcine heparins. Towards this goal, we have used 96-well plate based screening for development of a chitosan-based purification process for heparin and precursor polysaccharides. The unique pH responsive behavior of chitosan enables simplified capture of target heparin or related polysaccharides, under low pH and complex solution conditions, followed by elution under mildly basic conditions. The use of mild, basic recovery conditions are compatible with the chemical N-deacetylation/N-sulfonation step used in the bioengineered heparin process. Selective precipitation of glycosaminoglycans (GAGs) leads to significant removal of process related impurities such as proteins, DNA and endotoxins. Use of highly sensitive liquid chromatography-mass spectrometry and nuclear magnetic resonance analytical techniques reveal a minimum impact of chitosan-based purification on heparin product composition. PMID- 26147065 TI - GABAA receptor deficits predict recovery in patients with disorders of consciousness: A preliminary multimodal [(11) C]Flumazenil PET and fMRI study. AB - OBJECTIVES: Disorders of consciousness (DoC)-that is, unresponsive wakefulness syndrome/vegetative state and minimally conscious state-are debilitating conditions for which no reliable markers of consciousness recovery have yet been identified. Evidence points to the GABAergic system being altered in DoC, making it a potential target as such a marker. EXPERIMENTAL DESIGN: In our preliminary study, we used [(11) C]Flumazenil positron emission tomography to establish global GABAA receptor binding potential values and the local-to-global (LTG) ratio of these for specific regions. These values were then compared between DoC patients and healthy controls. In addition, they were correlated with behavioral improvements for the patients between the time of scanning and 3 months later. Functional magnetic resonance imaging resting-state functional connectivity was also calculated and the same comparisons made. PRINCIPAL OBSERVATIONS: lobal GABAA receptor binding was reduced in DoC, as was the LTG ratio in specifically the supragenual anterior cingulate. Both of these measures correlated with behavioral improvement after 3 months. In contrast to these measures of GABAA receptor binding, functional connectivity did not correlate with behavioral improvement. CONCLUSIONS: Our preliminary findings point toward GABAA receptor binding being a marker of consciousness recovery in DoC. PMID- 26147066 TI - Automatic single cell segmentation on highly multiplexed tissue images. AB - The combination of mass cytometry and immunohistochemistry (IHC) enables new histopathological imaging methods in which dozens of proteins and protein modifications can be visualized simultaneously in a single tissue section. The power of multiplexing combined with spatial information and quantification was recently illustrated on breast cancer tissue and was described as next-generation IHC. Robust, accurate, and high-throughput cell segmentation is crucial for the analysis of this new generation of IHC data. To this end, we propose a watershed based cell segmentation, which uses a nuclear marker and multiple membrane markers, the latter automatically selected based on their correlation. In comparison with the state-of-the-art segmentation pipelines, which are only using a single marker for object detection, we could show that the use of multiple markers can significantly increase the segmentation power, and thus, multiplexed information should be used and not ignored during the segmentation. Furthermore, we provide a novel, user-friendly open-source toolbox for the automatic segmentation of multiplexed histopathological images. PMID- 26147067 TI - Heterofunctional Magnetic Metal-Chelate-Epoxy Supports for the Purification and Covalent Immobilization of Benzoylformate Decarboxylase From Pseudomonas Putida and Its Carboligation Reactivity. AB - In this study, the combined use of the selectivity of metal chelate affinity chromatography with the capacity of epoxy supports to immobilize poly-His-tagged recombinant benzoylformate decarboxylase from Pseudomonas putida (BFD, E.C. 4.1.1.7) via covalent attachment is shown. This was achieved by designing tailor made magnetic chelate-epoxy supports. In order to selectively adsorb and then covalently immobilize the poly-His-tagged BFD, the epoxy groups (300 umol epoxy groups/g support) and a very small density of Co(2+)-chelate groups (38 umol Co(2+)/g support) was introduced onto magnetic supports. That is, it was possible to accomplish, in a simple manner, the purification and covalent immobilization of a histidine-tagged recombinant BFD. The magnetically responsive biocatalyst was tested to catalyze the carboligation reactions. The benzoin condensation reactions were performed with this simple and convenient heterogeneous biocatalyst and were comparable to that of a free-enzyme-catalyzed reaction. The enantiomeric excess (ee) of (R)-benzoin was obtained at 99 +/- 2% for the free enzyme and 96 +/- 3% for the immobilized enzyme. To test the stability of the covalently immobilized enzyme, the immobilized enzyme was reused in five reaction cycles for the formation of chiral 2-hydroxypropiophenone (2-HPP) from benzaldehyde and acetaldehyde, and it retained 96% of its original activity after five reaction cycles. PMID- 26147068 TI - When social inclusion is not enough: Implicit expectations of extreme inclusion in borderline personality disorder. AB - Increasing evidence suggests that individuals with borderline personality disorder (BPD) might feel rejected even when socially included by others. A psychological mechanism accounting for this response bias could be that objective social inclusion violates BPD patients' underlying implicit needs of "extreme" inclusion. Thus, this study investigated whether, during interpersonal exchanges, BPD patients report more rejection-related negative emotions and less feelings of social connection than controls unless they are faced with conditions of extreme social inclusion. Sixty-one BPD patients and 61 healthy controls completed a modified Cyberball paradigm. They were randomly assigned to a condition of ostracism, social inclusion, or overinclusion (a proxy for extreme social inclusion). They then rated their emotional states and feelings of social connection immediately and 20 min after the game. BPD patients reported greater levels of negative emotions than controls in the ostracism and the inclusion conditions, but not when overincluded. Furthermore, only for BPD participants was overinclusion associated with experiencing less negative emotions than the ostracism condition. However, BPD patients reported lower feelings of social connection than controls in any experimental situation. Thus, in BPD, a laboratory condition of "overinclusion" is associated with a reduction of negative emotions to levels comparable to those of control participants, but not with similar degrees of social connection. These results suggest that for BPD patients, even "including contexts" activate feelings of rejection. Their implicit expectations of idealized interpersonal inclusion may nullify the opportunity of experiencing "real" social connection and explain their distorted subjective experiences of rejection. PMID- 26147070 TI - Parsing the heterogeneity of psychopathy and aggression: Differential associations across dimensions and gender. AB - Psychopathy is a multidimensional construct that is broadly associated with both reactive (RA) and proactive (PA) aggression. Nevertheless, a consistent pattern of associations between psychopathy and these 2 aggression subtypes has yet to emerge because of methodological differences across studies. Moreover, research has yet to examine gender differences in the relation between dimensions of psychopathy and RA/PA. Accordingly, we examined the associations between psychopathy dimensions, as operationalized by 2 self-report instruments, and subtypes of aggression within a diverse sample of undergraduates (N = 1,158). Results confirmed that psychopathy is broadly associated with PA, as well as RA, with dimensions of psychopathy evidencing common and distinct associations with both raw and residual RA and PA scores. In both models of psychopathy, PA was significantly and positively associated with all dimensions, whereas RA was significantly negatively associated with interpersonal and affective dimensions, and significantly positively associated with dimensions related to an antisocial and impulsive lifestyle. Gender significantly moderated associations among dimensions of psychopathy and RA/PA, such that the antisocial/behavioral dimension of psychopathy was positively associated with PA for males, whereas the antisocial/behavioral dimension was positively associated with RA for females. Results suggest both generality and specificity of psychopathy dimensions as related to subtypes of aggression, as well as possible differential pathways from psychopathy to different subtypes of aggression in men and women. PMID- 26147069 TI - Exploring the association of deliberate self-harm with emotional relief using a novel Implicit Association Test. AB - Despite the growing consensus that negative reinforcement in the form of emotional relief plays a key role in the maintenance of deliberate self-harm (DSH), most of the research in this area has relied exclusively on self-report measures of the perceived motives for and emotional consequences of DSH. Thus, the primary aim of this study was to extend extant research on the role of emotional relief in DSH by examining the strength of the association of DSH with emotional relief using a novel version of the Implicit Association Test (IAT). The strength of the DSH-relief association among both participants with (vs. without) DSH and self-harming participants with (vs. without) BPD, as well as its associations with relevant clinical constructs (including DSH characteristics, self-reported motives for DSH, BPD pathology, and emotion dysregulation and avoidance) were examined in a community sample of young adults (113 with recent recurrent DSH; 135 without DSH). As hypothesized, results revealed stronger associations between DSH and relief among participants with versus without DSH, as well as among DSH participants with versus without BPD. Moreover, the strength of the DSH-relief association was positively associated with DSH frequency and versatility (both lifetime and at 6-month follow-up), BPD pathology, emotion dysregulation, experiential avoidance, and self-reported emotion relief motives for DSH. Findings provide support for theories emphasizing the role of emotional relief in DSH (particularly among individuals with BPD), as well as the construct validity, predictive utility, and incremental validity (relative to self-reported emotion relief motives) of this IAT. PMID- 26147071 TI - DINTO: Using OWL Ontologies and SWRL Rules to Infer Drug-Drug Interactions and Their Mechanisms. AB - The early detection of drug-drug interactions (DDIs) is limited by the diffuse spread of DDI information in heterogeneous sources. Computational methods promise to play a key role in the identification and explanation of DDIs on a large scale. However, such methods rely on the availability of computable representations describing the relevant domain knowledge. Current modeling efforts have focused on partial and shallow representations of the DDI domain, failing to adequately support computational inference and discovery applications. In this paper, we describe a comprehensive ontology for DDI knowledge (DINTO), which is the first formal representation of different types of DDIs and their mechanisms and its application in the prediction of DDIs. This project has been developed using currently available semantic web technologies, standards, and tools, and we have demonstrated that the combination of drug-related facts in DINTO and Semantic Web Rule Language (SWRL) rules can be used to infer DDIs and their different mechanisms on a large scale. The ontology is available from https://code.google.com/p/dinto/. PMID- 26147072 TI - Observing Electrokinetic Janus Particle-Channel Wall Interaction Using Microparticle Image Velocimetry. AB - Three-dimensional/two-component microparticle image velocimetry is used to examine the hydrodynamic flow patterns around metallodielectric Janus particles 15 MUm in diameter adjacent to insulating and conducting walls. Far from the walls, the observed flow patterns are in good qualitative agreement with previous experimental and analytical models. However, close to the conducting wall, strong electrohydrodynamic flows are observed at low frequencies, which result in fluid being injected toward the particle. The proximity of the metallic hemisphere to the conducting wall is also shown to produce a localized field gradient, which results in dielectrophoretic trapping of 300 nm polystyrene particles across a broad range of frequencies. PMID- 26147073 TI - Electrical Stimulation of Human Mesenchymal Stem Cells on Conductive Nanofibers Enhances their Differentiation toward Osteogenic Outcomes. AB - Tissue scaffolds allowing the behavior of the cells that reside within them to be controlled are of particular interest for tissue engineering. Herein, the preparation of conductive fiber-based bone tissue scaffolds (nonwoven mats of electrospun polycaprolactone with an interpenetrating network of polypyrrole and polystyrenesulfonate) is described that enable the electrical stimulation of human mesenchymal stem cells to enhance their differentiation toward osteogenic outcomes. PMID- 26147074 TI - Projection of the Dynamics of Electron Transfer Reaction in Dual Space onto the One-Dimensional Slower Reaction Coordinate Axis. AB - We have derived here for the first time an exact dynamical equation within the domain of classical mechanics for the time dependent density distribution function of one-dimensional reaction coordinate (RC) in the condensed phase for electron transfer reaction by projecting the dynamics of slower modes in multidimensional Liouville space starting with a given set of coordinates of the faster modes. After the faster modes were ensemble averaged, the dynamics of the whole system solely depends on the slower RC. To simplify the complicated equation into a tractable form, benchmark approximations are employed to reduce the formally exact equation into an equation similar to the Smoluchowski equation with a delocalized sink term. As a test case, a Hamiltonian for the solute solvent system modeled by quadratic functions for fast-relaxing vibrational and slow-relaxing polarization modes, respectively, has been considered. Interestingly, our simplified kinetic equation corresponding to this model Hamiltonian is transformed into the well-known phenomenological Sumi-Marcus equation. PMID- 26147075 TI - Assessment of computational tools for MRI RF dosimetry by comparison with measurements on a laboratory phantom. AB - This paper presents an extended comparison between numerical simulations using the different computational tools employed nowadays in electromagnetic dosimetry and measurements of radiofrequency (RF) electromagnetic field distributions in phantoms with tissue-simulating liquids at 64 MHz, 128 MHz and 300 MHz, adopting a customized experimental setup. The aim is to quantify the overall reliability and accuracy of RF dosimetry approaches at frequencies in use in magnetic resonance imaging transmit coils. Measurements are compared against four common techniques used for electromagnetic simulations, i.e. the finite difference time domain (FDTD), the finite integration technique (FIT), the boundary element method (BEM) and the hybrid finite element method-boundary element method (FEM BEM) approaches. It is shown that FDTD and FIT produce similar results, which generally are also in good agreement with those of FEM-BEM. On the contrary, BEM seems to perform less well than the other methods and shows numerical convergence problems in presence of metallic objects. Maximum uncertainties of about 30% (coverage factor k = 2) can be attributed to measurements regarding electric and magnetic field amplitudes. Discrepancies between simulations and experiments are found to be in the range from 10% to 30%. These values confirm other previously published results of experimental validations performed on a limited set of data and define the accuracy of our measurement setup. PMID- 26147076 TI - Simultaneous determination of three chloroacetic acids, three herbicides, and 12 anions in water by ion chromatography. AB - An ion chromatography method was developed for the simultaneous detection of three soluble herbicides (glyphosate, bentazone and picloram), three chlorine disinfection byproducts (monochloroacetic acid, dichloroacetic acid and trichloroacetic acid) and 12 anions in water (Cl(-), Br(-), SO4(2-), CO3(2-), ClO3(-), ClO4(-), BrO3(-), PO4(3-), NO2(-), NO3(-), CH3COO(-) and COO(-)). High linearity (r(2) > 0.996) was observed for all target analytes for each respective concentration range. The limit of detection and limit of quantitation were between 0.21-0.85 and 0.06-25.46 MUg/L, respectively. However, the interference effect of Cl(-), NO3(-) , SO4 (2-) and CO3(2-) on some target analytes must be considered during the analysis. Sample pre-treatment by a hydrogen column (H column) required to reduce the negative effect of CO3(2-). Additionally, sample pre-treatment by a sliver-hydrogen column (Ag-H-column) is required when Cl(-) > 100 mg/L and SO4(2-) < 50 mg/L, and pre-treatment by both a barium column (Ba column) and an H-column is required when Cl(-) > 100 mg/L and SO4(2-) > 50 mg/L. When Cl(-) > 100 mg/L, SO4(2-) > 50 mg/L and CO3(2-) > 20 mg/L, the sample pre treatment by either an Ag-H-Ba-column or an Ag-H-column and Ba-column is required to minimize interference. PMID- 26147077 TI - Phosphorylation-regulated crosslinking of gold nanoparticles: a new strategy for colorimetric detection of protein kinase activity. AB - Accurate and rapid detection of protein kinase activities is of great significance because protein kinases play important regulatory roles in many vital biological processes. Herein, we wish to report a facile colorimetric protein kinase assay based on the phosphorylation-tuned crosslinking of gold nanoparticles (GNPs) by using protein kinase A (PKA) as a proof-of-concept target. In this new strategy, a biotinylated peptide (biotin-LRRASLG) is used as the PKA-specific substrate. When mixed with streptavidin-functionalized GNPs (STV GNPs), the positively charged biotin-peptide will combine with different GNPs both through the specific STV-biotin binding and through electrostatic interactions, which will lead to the crosslinking and coagulation of GNPs. In contrast, under the catalysis of PKA, the biotin-peptide will be phosphorylated at the serine residue and its net charge will be obviously altered, which may significantly weaken the electrostatic interaction between the phosphopeptide and GNPs and thus effectively prevent the STV-GNPs from crosslinking and settlement. Therefore, by viewing the color changes of the GNPs, the PKA activity can be easily detected by the naked eye. PMID- 26147078 TI - Early herbivore alert matters: plant-mediated effects of egg deposition on higher trophic levels benefit plant fitness. AB - Induction of plant defences, specifically in response to herbivore attack, can save costs that would otherwise be needed to maintain defences even in the absence of herbivores. However, plants may suffer considerable damage during the time required to mount these defences against an attacker. This could be resolved if plants could respond to early cues, such as egg deposition, that reliably indicate future herbivory. We tested this hypothesis in a field experiment and found that egg deposition by the butterfly Pieris brassicae on black mustard (Brassica nigra) induced a plant response that negatively affected feeding caterpillars. The effect cascaded up to the third and fourth trophic levels (larval parasitoids and hyperparasitoids) by affecting the parasitisation rate and parasitoid performance. Overall, the defences induced by egg deposition had a positive effect on plant seed production and may therefore play an important role in the evolution of plant resistance to herbivores. PMID- 26147079 TI - Small-scale filament eruptions as the driver of X-ray jets in solar coronal holes. AB - Solar X-ray jets are thought to be made by a burst of reconnection of closed magnetic field at the base of a jet with ambient open field. In the accepted version of the 'emerging-flux' model, such a reconnection occurs at a plasma current sheet between the open field and the emerging closed field, and also forms a localized X-ray brightening that is usually observed at the edge of the jet's base. Here we report high-resolution X-ray and extreme-ultraviolet observations of 20 randomly selected X-ray jets that form in coronal holes at the Sun's poles. In each jet, contrary to the emerging-flux model, a miniature version of the filament eruptions that initiate coronal mass ejections drives the jet-producing reconnection. The X-ray bright point occurs by reconnection of the 'legs' of the minifilament-carrying erupting closed field, analogous to the formation of solar flares in larger-scale eruptions. Previous observations have found that some jets are driven by base-field eruptions, but only one such study, of only one jet, provisionally questioned the emerging-flux model. Our observations support the view that solar filament eruptions are formed by a fundamental explosive magnetic process that occurs on a vast range of scales, from the biggest mass ejections and flare eruptions down to X-ray jets, and perhaps even down to smaller jets that may power coronal heating. A similar scenario has previously been suggested, but was inferred from different observations and based on a different origin of the erupting minifilament. PMID- 26147080 TI - Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes. AB - During fertilization, an egg and a sperm fuse to form a new embryo. Eggs develop from oocytes in a process called meiosis. Meiosis in human oocytes is highly error-prone, and defective eggs are the leading cause of pregnancy loss and several genetic disorders such as Down's syndrome. Which genes safeguard accurate progression through meiosis is largely unclear. Here we develop high-content phenotypic screening methods for the systematic identification of mammalian meiotic genes. We targeted 774 genes by RNA interference within follicle-enclosed mouse oocytes to block protein expression from an early stage of oocyte development onwards. We then analysed the function of several genes simultaneously by high-resolution imaging of chromosomes and microtubules in live oocytes and scored each oocyte quantitatively for 50 phenotypes, generating a comprehensive resource of meiotic gene function. The screen generated an unprecedented annotated data set of meiotic progression in 2,241 mammalian oocytes, which allowed us to analyse systematically which defects are linked to abnormal chromosome segregation during meiosis, identifying progression into anaphase with misaligned chromosomes as well as defects in spindle organization as risk factors. This study demonstrates how high-content screens can be performed in oocytes, and allows systematic studies of meiosis in mammals. PMID- 26147081 TI - The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1. AB - Abnormal accumulation of triglycerides in the liver, caused in part by increased de novo lipogenesis, results in non-alcoholic fatty liver disease and insulin resistance. Sterol regulatory element-binding protein 1 (SREBP1), an important transcriptional regulator of lipogenesis, is synthesized as an inactive precursor that binds to the endoplasmic reticulum (ER). In response to insulin signalling, SREBP1 is transported from the ER to the Golgi in a COPII-dependent manner, processed by proteases in the Golgi, and then shuttled to the nucleus to induce lipogenic gene expression; however, the mechanisms underlying enhanced SREBP1 activity in insulin-resistant obesity and diabetes remain unclear. Here we show in mice that CREB regulated transcription coactivator 2 (CRTC2) functions as a mediator of mTOR signalling to modulate COPII-dependent SREBP1 processing. CRTC2 competes with Sec23A, a subunit of the COPII complex, to interact with Sec31A, another COPII subunit, thus disrupting SREBP1 transport. During feeding, mTOR phosphorylates CRTC2 and attenuates its inhibitory effect on COPII-dependent SREBP1 maturation. As hepatic overexpression of an mTOR-defective CRTC2 mutant in obese mice improved the lipogenic program and insulin sensitivity, these results demonstrate how the transcriptional coactivator CRTC2 regulates mTOR-mediated lipid homeostasis in the fed state and in obesity. PMID- 26147082 TI - Universal allosteric mechanism for Galpha activation by GPCRs. AB - G protein-coupled receptors (GPCRs) allosterically activate heterotrimeric G proteins and trigger GDP release. Given that there are ~800 human GPCRs and 16 different Galpha genes, this raises the question of whether a universal allosteric mechanism governs Galpha activation. Here we show that different GPCRs interact with and activate Galpha proteins through a highly conserved mechanism. Comparison of Galpha with the small G protein Ras reveals how the evolution of short segments that undergo disorder-to-order transitions can decouple regions important for allosteric activation from receptor binding specificity. This might explain how the GPCR-Galpha system diversified rapidly, while conserving the allosteric activation mechanism. PMID- 26147084 TI - Prognostic factors and risk classifications for patients with metastatic renal cell carcinoma. AB - The introduction of molecular-targeted therapy has made dramatical changes to treatment for metastatic renal cell carcinoma. Currently, there are four vascular endothelial growth factor receptor-tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors in Japan. For the appropriate clinical use of these molecular-targeted drugs, the identification of prognostic and/or predictive factors in patients who received these drugs is required. Although molecular biological and genetic factors that determine the prognosis of patients with metastatic renal cell carcinoma have been reported, most of these factors are problematic in that the number of patients analyzed was small. In contrast, clinicopathological prognostic factors, including the practice of cytoreductive nephrectomy, pathological findings, metastatic sites and metastasectomy, and abnormal inflammatory response, have been identified by analyzing a relatively large number of patients. Several prognostic classification models that were developed by combining these clinicopathological factors are widely used in not only clinical trials, but also routine clinical practice. However, the quality of these prognostic models is considered to be insufficient regarding prognostic prediction of metastatic renal cell carcinoma patients and, thus, requires further improvements. Recently, basic and clinical studies have been extensively carried out for the identification of promising informative markers and for understanding molecular mechanisms of resistance to molecular-targeted drugs in metastatic renal cell carcinoma patients. The present review considers ongoing translational research efforts on clinicopathological, molecular biological, and genetic prognostic and/or predictive factors for metastatic renal cell carcinoma patients in the era of molecular-targeted therapy, and discusses the clinical implications of these findings. PMID- 26147083 TI - Parent stem cells can serve as niches for their daughter cells. AB - Stem cells integrate inputs from multiple sources. Stem cell niches provide signals that promote stem cell maintenance, while differentiated daughter cells are known to provide feedback signals to regulate stem cell replication and differentiation. Recently, stem cells have been shown to regulate themselves using an autocrine mechanism. The existence of a 'stem cell niche' was first postulated by Schofield in 1978 to define local environments necessary for the maintenance of haematopoietic stem cells. Since then, an increasing body of work has focused on defining stem cell niches. Yet little is known about how progenitor cell and differentiated cell numbers and proportions are maintained. In the airway epithelium, basal cells function as stem/progenitor cells that can both self-renew and produce differentiated secretory cells and ciliated cells. Secretory cells also act as transit-amplifying cells that eventually differentiate into post-mitotic ciliated cells . Here we describe a mode of cell regulation in which adult mammalian stem/progenitor cells relay a forward signal to their own progeny. Surprisingly, this forward signal is shown to be necessary for daughter cell maintenance. Using a combination of cell ablation, lineage tracing and signalling pathway modulation, we show that airway basal stem/progenitor cells continuously supply a Notch ligand to their daughter secretory cells. Without these forward signals, the secretory progenitor cell pool fails to be maintained and secretory cells execute a terminal differentiation program and convert into ciliated cells. Thus, a parent stem/progenitor cell can serve as a functional daughter cell niche. PMID- 26147085 TI - Multifunctional hybrid-carbon nanotubes: new horizon in drug delivery and targeting. AB - Carbon nanotubes (CNTs) have emerged as an intriguing nanotechnological tool for numerous biomedical applications including biocompatible modules for the bioactives delivery ascribed to their unique properties, such as greater loading efficiency, biocompatibility, non-immunogenicity, high surface area and photoluminescence, that make them ideal candidate in pharmaceutical and biomedical science. The design of multifunctional hybrid-CNTs for drug delivery and targeting may differ from the conventional drug delivery system. The conventional nanocarriers have few limitations, such as inappropriate availability of surface-chemical functional groups for conjugation, low entrapment/loading efficiency as well as stability as per ICH guidelines with generally regarded as safe (GRAS) prominences. The multifunctional hybrid-CNTs will sparked and open a new door for researchers, scientist of the pharmaceutical and biomedical arena. This review summarizes the vivid aspects of CNTs like characterization, supramolecular chemistry of CNTs-dendrimer, CNTs-nanoparticles, CNTs-quantum dots conjugate for delivery of bioactives, not discussed so far. PMID- 26147086 TI - Intratester and Intertester Reliability of Toe Pressure Measurements in People with and Without Diabetes Performed by Podiatric Physicians. AB - BACKGROUND: Toe pressures and the toe brachial index (TBI) represent possible screening tools for peripheral arterial disease; however, limited evidence is available regarding their reliability. The aim of this study was to determine intratester and intertester reliability of toe systolic pressure and the TBI in participants with and without diabetes performed by podiatric physicians. METHODS: Two podiatric physicians performed toe and brachial pressure measurements on 80 participants, 40 with and 40 without diabetes, during two testing sessions using photoplethysmography and Doppler probe. Intraclass correlation coefficients (ICCs) and 95% limits of agreement were determined. RESULTS: In people with diabetes, intratester reliability of toe pressure measurement was excellent for both testers (ICCs, 0.84 and 0.82). Reliability of the TBI was good (ICCs, 0.72 and 0.75) and brachial pressure fair (ICCs, 0.43 and 0.55). The intertester reliability of toe pressure (ICC, 0.82) and the TBI (ICC, 0.80) was excellent. Intertester reliability of brachial pressure was reduced in people with diabetes (ICC, 0.49). In age-matched participants, intratester reliability of toe pressure measurement was excellent for both testers (ICCs, 0.83 and 0.87), and reliability of the TBI (ICCs, 0.74 and 0.80) and brachial pressure (ICCs, 0.73 and 0.78) was good to excellent. Intertester reliability of toe pressure (ICC, 0.84), the TBI (ICC, 0.81), and brachial pressure (ICC, 0.77) was excellent. CONCLUSIONS: Toe pressures and the TBI demonstrated excellent reliability in people with and without diabetes and can be an effective component of lower-extremity vascular screening. However, wide limits of agreement relative to blood pressure values for both cohorts indicate that results should be interpreted with caution. PMID- 26147087 TI - The AKT1 isoform plays a dominant role in the survival and chemoresistance of chronic lymphocytic leukaemia cells. PMID- 26147088 TI - Biodegradable poly(vinyl alcohol)/polyoxalate electrospun nanofibers for hydrogen peroxide-triggered drug release. AB - Release of drugs in a controlled and sustainable manner is of great interest for treating some inflammatory diseases, drug delivery, and cosmetics. In this work, we demonstrated the control release of a drug from composite nanofibers mediated by hydrogen peroxide. Composite nanofibers of polyvinyl alcohol (PVA)/polyoxalate (PVA/POX NFs) blended at various weight ratios were successfully prepared by electrospinning. Rhodamine B (RB) was used as a model of drug and was initially loaded into the POX portion. The morphology of NFs was characterized using scanning electron microscopy (SEM). The functional groups presented in the NFs were characterized using IR spectroscopy. In vitro release behavior and cell toxicity of nanofibers were also investigated using the MTT assay. The results indicated that POX content had a significant effect on the size and release profiles of nanofibers. Microstructure analysis revealed that sizes of PVA/POX NFs increased with increasing POX content, ranging from 214 to 422 nm. Release profiles of RB at 37 degrees C were non-linear and showed different release mechanisms. The mechanism of drug release depended on the chemical composition of the NFs. RB release from the NFs with highest POX content was caused by the degradation of the nanofiber matrix, whereas the RB release in lower POX content NFs was caused by diffusion. The NFs with POX showed a loss of structural integrity in the presence of hydrogen peroxide as seen using SEM. The MTT assay showed that composite nanofibers had minimal cytotoxicity. We anticipate that nanofibrous PVA/POX can potentially be used to target numerous inflammatory diseases that overproduce hydrogen peroxide and may become a potential candidate for use as a local drug delivery vehicle. PMID- 26147089 TI - Allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic syndrome: Experience of the Argentinean Group of Bone Marrow Transplantation (GATMO). AB - INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative approach for patients with myelodysplastic syndrome (MDS). METHODS: In this multicenter retrospective study, we analyzed the outcome of adult patients with MDS who underwent AHSCT in Argentina and evaluated the prognostic factors associated with progression-free survival (PFS), overall survival (OS), cumulative incidence (CI) of relapse, and non-relapse mortality (NRM). RESULTS: We analyzed data from 87 adults (median age: 43 years, range 18-66) who underwent SCT after myeloablative (n = 60) or non-myeloablative conditioning (n = 27), and from related (n = 62) or unrelated (n = 25) donors. For all patients, unadjusted 4-year PFS and OS were 37% and 38%, respectively; no significant differences were found between recipients of related or unrelated donors. One-year CI of relapse and NRM were 21% and 20%, respectively. In the multivariate analysis, intermediate disease risk index (DRI) and acute graft versus host disease AGVHD of all grades (I-IV) were independent variables associated with better PFS and lower relapse CI; only intermediate DRI was associated with better OS. CONCLUSIONS: AHSCT is a feasible procedure in Argentina, with more than 30% of the patients achieving long-term survival. Recipients with unrelated donors had at least similar outcome than those with related donors. DRI may be useful to identify patients at higher risk of relapse after transplantation. PMID- 26147091 TI - Odontogenic Sinusitis an underappreciated diagnosis: Our experience. PMID- 26147090 TI - A role for the small GTPase Rac1 in vaccinia actin-based motility. AB - Vaccinia virus dissemination relies on the recruitment of the nucleation promoting factor N-WASP underneath cell-associated extracellular virus (CEVs) and subsequent recruitment and activation of the ARP2/3 complex, a major actin nucleator of the host cell. We have recently discovered that, in addition to the N-WASP/ARP2/3 pathway, vaccinia actin-based motility also relies on the small GTPase Rac1 and its downstream effector the formin-type actin nucleator FHOD1. Here we discuss the potential signaling mechanisms supporting the integration of the N-WASP/ARP2/3 and Rac1/FHOD1 pathways. We suggest the existence of a receptor tyrosine kinase family member that would integrate the Src-dependent activation of the N-WASP/ARP2/3 pathway and the GTP exchange factor-dependent activation of the Rac1/FHOD1 pathway. PMID- 26147093 TI - Potential Efficiency of Riparian Vegetated Buffer Strips in Intercepting Soluble Compounds in the Presence of Subsurface Preferential Flows. AB - Buffer strips have been widely recognized as to promote infiltration, deposition and sorption of contaminants for protecting surface water against agricultural contamination. However, such strips do not intercept all contaminants, particularly soluble ones. Although preferential flow (PF) has been suggested as one factor among several decreasing the efficiency of buffer strips, the mechanisms involved are not well understood. This project examines buffer strip efficiency at intercepting solutes when subsurface PF occurs. Two soluble sorbed tracers, FD&C Blue #1 and rhodamine WT, were applied on an agricultural sandy loam soil to evaluate the ability of a naturally vegetated buffer strip to intercept soluble contaminants. Rhodamine was applied about 15 m from the creek, while the Blue was applied 15 m to 165 m from the creek. Tracer concentration was measured over a two-year period in both the creek and the buffer strip through soil and water samples. Although the tracers traveled via different pathways, they both quickly moved toward the creek, passing beneath the buffer strip through the soil matrix. Our results demonstrate that the risk of water contamination by soluble contaminants is high in such systems, even when a well vegetated buffer strip is used. The design of buffer strips should be modified to account for underground bypass, either by using plants that have deep, fine roots that do not favour PF or by adding a filter extending deep underground that can be regularly changed. PMID- 26147092 TI - Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease. AB - Transthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progression. Since non mutated transthyretin also forms amyloid in systemic senile amyloidosis and some mutation bearers are asymptomatic throughout their lives, non-genetic factors must also be involved in transthyretin amyloidosis. We discovered, using a differential proteomics approach, that extracellular chaperones such as fibrinogen, clusterin, haptoglobin, alpha-1-anti-trypsin and 2-macroglobulin are overrepresented in transthyretin amyloidosis. Our data shows that a complex network of extracellular chaperones are over represented in human plasma and we speculate that they act synergistically to cope with amyloid prone proteins. Proteostasis may thus be as important as point mutations in transthyretin amyloidosis. PMID- 26147094 TI - PhenStat: A Tool Kit for Standardized Analysis of High Throughput Phenotypic Data. AB - The lack of reproducibility with animal phenotyping experiments is a growing concern among the biomedical community. One contributing factor is the inadequate description of statistical analysis methods that prevents researchers from replicating results even when the original data are provided. Here we present PhenStat--a freely available R package that provides a variety of statistical methods for the identification of phenotypic associations. The methods have been developed for high throughput phenotyping pipelines implemented across various experimental designs with an emphasis on managing temporal variation. PhenStat is targeted to two user groups: small-scale users who wish to interact and test data from large resources and large-scale users who require an automated statistical analysis pipeline. The software provides guidance to the user for selecting appropriate analysis methods based on the dataset and is designed to allow for additions and modifications as needed. The package was tested on mouse and rat data and is used by the International Mouse Phenotyping Consortium (IMPC). By providing raw data and the version of PhenStat used, resources like the IMPC give users the ability to replicate and explore results within their own computing environment. PMID- 26147096 TI - Evaluating the Early Benefit of Quadrivalent HPV Vaccine on Genital Warts in Belgium: A Cohort Study. AB - Genital warts (GWs) are common, with about 5% to 10% of people having at least one episode in their lifetime. They develop about 2-3 months after infection with human papillomavirus (HPV) genotypes 6 and 11. The prophylactic quadrivalent HPV vaccine (qHPV), protects against HPV6/11 infections and diseases. In Belgium, HPV vaccines started to be reimbursed in 2007 and have been fully reimbursed since December 2008 for women 12 to 18 years old. This study aimed at evaluating the real-life benefit of qHPV vaccine introduction in Belgium on GWs by measuring both vaccine impact (VI) at a population level and the direct effect of the qHPV vaccine at an individual level (vaccine effectiveness (VE)), using data from a large sick-fund (MLOZ) reimbursement database. A first reimbursement for imiquimod (most common first-line GWs treatment in Belgium) was used as a surrogate for a first GWs episode; reimbursement of qHPV vaccine was used as surrogate for vaccination. VI was estimated by comparing the incidence of GWs before and after qHPV vaccine introduction in Belgium (ecologic evaluation). VE was assessed by comparing GWs incidences in vaccinated vs. unvaccinated women, among women eligible for HPV vaccination. VI was evaluated in 9,223,384 person years. Overall, GWs incidence rates decreased significantly between the pre- and post-vaccination periods (-8.1% (95% CI: -15.3; -0.3) for men and women aged 18 59 years. This decrease was highest in women targeted by the HPV vaccination programme (-72.1% (95% CI: -77.9; -64.7) in women aged 16-22 years, with a 43% vaccine uptake in 2013). A significant decrease was also observed in men aged 16 22 years (-51.1%, 95%CI: -67.6; -26.2), suggesting herd-protection. VE was evaluated in 369,881 person-years. Age-adjusted VE for fully vaccinated women was 88.0% (95% CI: 79.4; 93.0). VE was higher when the first dose was given younger and remained high for over 4 years post-vaccination in all ages. High VI and VE of the qHPV vaccine were observed in a real-life setting in Belgium. PMID- 26147095 TI - Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine. AB - Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity. PMID- 26147097 TI - Sociodemographics, Comorbidities, Healthcare Utilization and Work Productivity in Japanese Patients with Adult ADHD. AB - OBJECTIVES: This study compared the sociodemographic characteristics, comorbidities, healthcare resource utilization, and work productivity among Japanese adults who reported being diagnosed with attention-deficit/hyperactivity disorder (ADHD) to those of a non-ADHD control population. METHODS: Data for this study were captured from an online survey of adults in Japan conducted by Kantar Health using consumer panels. A total of 84 survey participants reported they had received a diagnosis of ADHD from a physician. Survey responses pertaining to functional status and resource utilization from this ADHD group were compared to those from a non-ADHD control group of 100 participants. Comparisons between the ADHD and non-ADHD groups were made using chi-square tests for categorical variables and t-tests for continuous variables. RESULTS: Participants in the ADHD group were on average slightly younger with a higher proportion of males. ADHD respondents reported significantly more comorbid depression, sleep difficulties, headaches, and anxiety than non-ADHD controls. Over the previous 6 months, the ADHD group made more visits to healthcare providers and the emergency room, and had more hospitalizations than non-ADHD controls. The ADHD group also rated their overall health status lower than the non-ADHD control group. Respondents with ADHD reported a significantly higher degree of health-related work impairment compared to non-ADHD, with greater absenteeism and decreased work productivity. The ADHD group indicated their symptoms negatively impacted relationships, self esteem, and regular daily activities. CONCLUSIONS: Japanese adults with ADHD face a substantial burden of illness, including lower overall health status, increased number of comorbidities, greater healthcare utilization, and significant health related occupational impairment compared to those without ADHD. Additional research is needed to develop a better understanding of both the consequences and treatment approaches for Japanese adults with ADHD. PMID- 26147099 TI - Are Sex Drive and Hypersexuality Associated with Pedophilic Interest and Child Sexual Abuse in a Male Community Sample? AB - Although much is currently known about hypersexuality (in the form of excessive sexual behavior) among sexual offenders, the degree to which hypersexual behavior is linked to paraphilic and especially pedophilic interests in non-forensic populations has not been established.The purpose of the present study was to elucidate the associations between total sexual outlets(TSO) and other sex drive indicators, antisocial behavior, pedophilic interests, and sexual offending behavior in a large population-based community sample of males. The sample included 8,718 German men who participated in an online study. Hypersexual behavior as measured by self-reported TSO, self-reported sex drive, criminal history, and pedophilic interests were assessed. In moderated hierarchical logistic regression analyses self-reported contact sexual offending against children was linked to sexual fantasizing about children and anti sociality.There was no association between aggregated sex drive, and sexual abusive behaviour in the multivariate analyses. In contrast, self-reported child pornography consumption was associated with sex drive, sexual fantasies involving children, and anti sociality. Nevertheless, in convicted sexual offenders anti sociality, sexual preoccupation (like hypersexuality), and pedophilic interest are important predictors of sexual reoffending against prepubescent children.Therefore, in clinical practice an assessment of criminal history and pedophilic interests in hypersexual individuals and vice versa hypersexuality in antisocial or pedophilic men should be considered [corrected]. PMID- 26147098 TI - Conserved Noncoding Sequences Regulate lhx5 Expression in the Zebrafish Forebrain. AB - The LIM homeobox family protein Lhx5 plays important roles in forebrain development in the vertebrates. The lhx5 gene exhibits complex temporal and spatial expression patterns during early development but its transcriptional regulation mechanisms are not well understood. Here, we have used transgenesis in zebrafish in order to define regulatory elements that drive lhx5 expression in the forebrain. Through comparative genomic analysis we identified 10 non-coding sequences conserved in five teleost species. We next examined the enhancer activities of these conserved non-coding sequences with Tol2 transposon mediated transgenesis. We found a proximately located enhancer gave rise to robust reporter EGFP expression in the forebrain regions. In addition, we identified an enhancer located at approximately 50 kb upstream of lhx5 coding region that is responsible for reporter gene expression in the hypothalamus. We also identify an enhancer located approximately 40 kb upstream of the lhx5 coding region that is required for expression in the prethalamus (ventral thalamus). Together our results suggest discrete enhancer elements control lhx5 expression in different regions of the forebrain. PMID- 26147100 TI - Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences. AB - Computational protein design has found great success in engineering proteins for thermodynamic stability, binding specificity, or enzymatic activity in a 'single state' design (SSD) paradigm. Multi-specificity design (MSD), on the other hand, involves considering the stability of multiple protein states simultaneously. We have developed a novel MSD algorithm, which we refer to as REstrained CONvergence in multi-specificity design (RECON). The algorithm allows each state to adopt its own sequence throughout the design process rather than enforcing a single sequence on all states. Convergence to a single sequence is encouraged through an incrementally increasing convergence restraint for corresponding positions. Compared to MSD algorithms that enforce (constrain) an identical sequence on all states the energy landscape is simplified, which accelerates the search drastically. As a result, RECON can readily be used in simulations with a flexible protein backbone. We have benchmarked RECON on two design tasks. First, we designed antibodies derived from a common germline gene against their diverse targets to assess recovery of the germline, polyspecific sequence. Second, we design "promiscuous", polyspecific proteins against all binding partners and measure recovery of the native sequence. We show that RECON is able to efficiently recover native-like, biologically relevant sequences in this diverse set of protein complexes. PMID- 26147102 TI - Self-Efficacy to Drive While Intoxicated: Insights into the Persistence of Alcohol-Impaired Driving. AB - BACKGROUND: Scant research has examined event-level risk factors for impaired driving in natural drinking settings. This study assessed driving self-efficacy among intoxicated individuals to better understand decision-making about alcohol impaired driving at night after exiting on-premise drinking establishments. METHODS: Interview and breath test data were collected from bar patrons (n = 512) exiting 2 college bar districts in Florida and Texas. RESULTS: Results from a multivariable linear regression model indicated that self-efficacy to drive while intoxicated was more strongly associated with situational variables, that is, perceived drunkenness and self-estimated blood alcohol concentration than patron traits, that is, past-year history of drinking, risk proneness, and sex. A large proportion of bar patrons, particularly men, expressed confidence in their ability to drive, despite being highly intoxicated. Moreover, the majority of legally intoxicated patrons who were confident in their ability to drive were aware of their high level of intoxication. CONCLUSIONS: Emphasis should be placed on the enactment and enforcement of policies and laws to prevent alcohol-impaired driving. PMID- 26147101 TI - Dysregulation of Autonomic Nervous System in Chagas' Heart Disease Is Associated with Altered Adipocytokines Levels. AB - BACKGROUND: Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD. METHODS AND RESULTS: Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL 6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group. CONCLUSIONS: We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in patients with ECG abnormalities and normal systolic function at rest. Adipocytokines levels (adiponectin and leptin) were associated with ANS parameters in Chagas' heart disease. PMID- 26147103 TI - Daily Temperature Fluctuations Alter Interactions between Closely Related Species of Marine Nematodes. AB - In addition to an increase in mean temperature, climate change models predict decreasing amplitudes of daily temperature fluctuations. In temperate regions, where daily and seasonal fluctuations are prominent, such decreases in daily temperature fluctuations can have a pronounced effect on the fitness of species and on the outcome of species interactions. In this study, the effect of a temperature regime with daily fluctuations versus a constant temperature on the fitness and interspecific interactions of three cryptic species of the marine nematode species complex of Litoditis marina (Pm I, Pm III and Pm IV) were investigated. In a lab experiment, different combinations of species (monospecific treatment: Pm I and Pm IV and Pm III alone; two-species treatment: Pm I + Pm IV; three-species treatment: Pm I + Pm IV + Pm III) were subjected to two different temperature regimes: one constant and one fluctuating temperature. Our results showed that fluctuating temperature had minor or no effects on the population fitness of the three species in monocultures. In contrast, interspecific interactions clearly influenced the fitness of all three species, both positively and negatively. Temperature regime did have a substantial effect on the interactions between the species. In the two-species treatment, temperature regime altered the interaction from a sort of mutualism to commensalism. In addition, the strength of the interspecific interactions changed depending on the temperature regime in the three-species treatment. This experiment confirms that interactions between the species can change depending on the abiotic environment; these results show that it is important to incorporate the effect of fluctuations on interspecific interactions to predict the effect of climate change on biodiversity. PMID- 26147104 TI - Requirement of miR-9-dependent regulation of Myocd in PASMCs phenotypic modulation and proliferation induced by hepatopulmonary syndrome rat serum. AB - Hepatopulmonary syndrome (HPS) is characterized by a triad of severe liver disease, intrapulmonary vascular dilation and hypoxaemia. Pulmonary vascular remodelling (PVR) is a key feature of HPS pathology. Our previous studies have established the role of the pulmonary artery smooth muscle cell (PASMC) phenotypic modulation and proliferation in HPS-associated PVR. Myocardin, a robust transcriptional coactivator of serum response factor, plays a critical role in the vascular smooth muscle cell phenotypic switch. However, the mechanism regulating myocardin upstream signalling remains unclear. In this study, treatment of rat PASMCs with serum drawn from common bile duct ligation rats, which model symptoms of HPS, resulted in a significant increase in miR-9 expression correlated with a decrease in expression of myocardin and the phenotypic markers SM-alpha-actin and smooth muscle-specific myosin heavy chain (SM-MHC). Furthermore, miRNA functional analysis and luciferase reporter assay demonstrated that miR-9 effectively regulated myocardin expression by directly binding to its 3'-untranslated region. Both the knockdown of miR-9 and overexpression of myocardin effectively attenuated the HPS rat serum-induced phenotype switch and proliferation of PASMCs. Taken together, the findings of our present study demonstrate that miR-9 is required in HPS rat serum-induced phenotypic modulation and proliferation of PASMCs for targeting of myocardin and that miR-9 may serve as a potential therapeutic target in HPS. PMID- 26147105 TI - The Histone Methyltransferase Inhibitor A-366 Uncovers a Role for G9a/GLP in the Epigenetics of Leukemia. AB - Histone methyltransferases are epigenetic regulators that modify key lysine and arginine residues on histones and are believed to play an important role in cancer development and maintenance. These epigenetic modifications are potentially reversible and as a result this class of enzymes has drawn great interest as potential therapeutic targets of small molecule inhibitors. Previous studies have suggested that the histone lysine methyltransferase G9a (EHMT2) is required to perpetuate malignant phenotypes through multiple mechanisms in a variety of cancer types. To further elucidate the enzymatic role of G9a in cancer, we describe herein the biological activities of a novel peptide competitive histone methyltransferase inhibitor, A-366, that selectively inhibits G9a and the closely related GLP (EHMT1), but not other histone methyltransferases. A-366 has significantly less cytotoxic effects on the growth of tumor cell lines compared to other known G9a/GLP small molecule inhibitors despite equivalent cellular activity on methylation of H3K9me2. Additionally, the selectivity profile of A-366 has aided in the discovery of a potentially important role for G9a/GLP in maintenance of leukemia. Treatment of various leukemia cell lines in vitro resulted in marked differentiation and morphological changes of these tumor cell lines. Furthermore, treatment of a flank xenograft leukemia model with A-366 resulted in growth inhibition in vivo consistent with the profile of H3K9me2 reduction observed. In summary, A-366 is a novel and highly selective inhibitor of G9a/GLP that has enabled the discovery of a role for G9a/GLP enzymatic activity in the growth and differentiation status of leukemia cells. PMID- 26147106 TI - Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing. AB - BACKGROUND: In multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions. OBJECTIVES: To evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation. METHODS: Before Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing-up, during metronomic deep-breathing, Valsalva-maneuver, and "sustained handgrip-exercise" in 21 patients with relapsing-remitting MS, and 20 healthy persons. We calculated sympathetic and parasympathetic cardiovascular parameters, including low- (LF) and high-frequency (HF) powers of RRI- and BP-oscillations, RRI-RMSSDs, RRI- and BP-changes during handgrip-exercise, parasympathetic heart rate-slowing in relation to BP-overshoot after Valsalva-strain-release. We compared values of healthy persons and patients with and without prolonged heart rate slowing after Fingolimod-initiation (ANOVA; significance: p<0.05). RESULTS: Upon Fingolimod-initiation, 7/21 patients had prolonged HR-slowing. Before Fingolimod, these patients had higher resting BP and higher BP increase during handgrip-exercise than had the other participants (p<0.05). They did not reduce parasympathetic HR-parameters upon standing-up. After Valsalva-strain-release, their parasympathetic HR-slowing in response to BP-overshoot was four times higher than in the other participants (p<0.05). CONCLUSIONS: The autonomic cardiovascular dysfunction in MS-patients with delayed HR-re-acceleration upon Fingolimod-initiation suggests that MS-related central autonomic lesions compromise HR-re-acceleration upon Fingolimod. TRIAL REGISTRATION: German Clinical Trial Register DRKS00004548 http://drks-neu.uniklinik freiburg.de/drks_web/setLocale_EN.do. PMID- 26147107 TI - Reversible Dissolution of Microdomains in Detergent-Resistant Membranes at Physiological Temperature. AB - The formation of lipid microdomains ("rafts") is presumed to play an important role in various cellular functions, but their nature remains controversial. Here we report on microdomain formation in isolated, detergent-resistant membranes from MDA-MB-231 human breast cancer cells, studied by atomic force microscopy (AFM). Whereas microdomains were readily observed at room temperature, they shrunk in size and mostly disappeared at higher temperatures. This shrinking in microdomain size was accompanied by a gradual reduction of the height difference between the microdomains and the surrounding membrane, consistent with the behaviour expected for lipids that are laterally segregated in liquid ordered and liquid disordered domains. Immunolabeling experiments demonstrated that the microdomains contained flotillin-1, a protein associated with lipid rafts. The microdomains reversibly dissolved and reappeared, respectively, on heating to and cooling below temperatures around 37 degrees C, which is indicative of radical changes in local membrane order close to physiological temperature. PMID- 26147108 TI - Increased risk of liver cirrhosis for tuberculosis infection: response to Shen. PMID- 26147109 TI - Editorial: fibre and FODMAPs in constipation and irritable bowel syndrome. PMID- 26147110 TI - Letter: chronic constipation - a warning sign for oxidative stress? PMID- 26147111 TI - Letter: usefulness of HCC risk scores in HCV patients who fail pegylated interferon/ribavirin. PMID- 26147112 TI - Letter: chronic constipation - a warning sign for oxidative stress? Author's reply. PMID- 26147113 TI - Letter: colestyramine for chronic unexplained diarrhoea - promising but much to learn? PMID- 26147114 TI - Letter: proton pump inhibitors, hypergastrinaemia and the risk of gastric neoplasia. PMID- 26147115 TI - The Impact of Visual Aids and Enhanced Training on the Delivery of Positive Health, Dignity, and Prevention Messages to Adult Patients Living with HIV in Rural North Central Mozambique. AB - INTRODUCTION: Positive health, dignity, and prevention (PHDP) interventions target people living with HIV and AIDS (PLHIV) to promote well-being and prevent onward transmission. Concern that increased life expectancy and improved well being would lead to increased risky sexual behaviour and subsequent HIV transmission motivated researchers to test novel strategies to support treatment adherence, encourage safer sex, STI treatment and partner testing, prevention of mother to child transmission, and support uptake of family planning. METHODS: We assessed the number and type of PHDP messages delivered to PLHIV before and after the implementation of an educational intervention for health providers combined with the distribution of visual job aids and monthly technical assistance. RESULTS: From April 21, 2013 to March 20, 2014, we documented 54,731 clinical encounters at three rural health centres in Zambezia province, Mozambique from 9,248 unique patients. The percentage of patients who received all seven PHDP messages during their last three visits was 1.9% pre-intervention vs. 13.6% post- intervention (p=<0.001). Younger patients (25 years vs. 35) and those with a recent HIV diagnosis (two weeks vs. two years) had higher odds of receiving any PHDP message (Odds Ratio [OR]: 1.22 and 2.79, respectively). Patients >59 days late collecting medications were not more likely to receive adherence messages than adherent patients (p=0.17). DISCUSSION: Targeting HIV prevention efforts to PLHIV is an effective HIV prevention approach to eliminate HIV transmission. Despite intensive training and support, PHDP message delivery remained unacceptably low in rural Mozambique. Patients at high risk for treatment abandonment were not more likely to be counselled about adherence and support measures, something that needs to be addressed. CONCLUSIONS: We need to develop novel strategies to motivate health care providers to deliver these messages more consistently to all patients and develop a system that assists counsellors and clinicians to quickly and effectively determine which messages should be delivered. PMID- 26147116 TI - Long-term neurodevelopmental outcome after selective feticide in monochorionic pregnancies. AB - OBJECTIVE: To assess the incidence of and risk factors for adverse long-term neurodevelopmental outcome in complicated monochorionic pregnancies treated with selective feticide at our centre between 2000 and 2011. DESIGN: Observational cohort study. SETTING: National referral centre for fetal therapy (Leiden University Medical Centre, the Netherlands). POPULATION: Neurodevelopmental outcome was assessed in 74 long-term survivors. METHODS: Children, at least 2 years of age, underwent an assessment of neurologic, motor and cognitive development using standardised psychometric tests and the parents completed a behavioural questionnaire. MAIN OUTCOME MEASURES: A composite outcome termed neurodevelopmental impairment including cerebral palsy (GMFCS II-V), cognitive and/or motor test score of <70, bilateral blindness or bilateral deafness requiring amplification. RESULTS: A total of 131 monochorionic pregnancies were treated with selective feticide at the Leiden University Medical Centre. Overall survival rate was 88/131 (67%). Long-term outcome was assessed in 74/88 (84%). Neurodevelopmental impairment was detected in 5/74 [6.8%, 95% confidence interval (CI), 1.1-12.5] of survivors. Overall adverse outcome, including perinatal mortality or neurodevelopmental impairment was 48/131 (36.6%). In multivariate analysis, parental educational level was associated with cognitive test scores (regression coefficient B 3.9, 95% CI 1.8-6.0). Behavioural problems were reported in 10/69 (14.5%). CONCLUSIONS: Adverse long-term outcome in survivor twins of complicated monochorionic pregnancies treated with selective feticide appears to be more prevalent than in the general population. Cognitive test scores were associated with parental educational level. TWEETABLE ABSTRACT: Neurodevelopmental impairment after selective feticide was detected in 5/74 (6.8%, 95% CI 1.1-12.5) of survivors. PMID- 26147117 TI - The Tinkerbell (Tink) Mutation Identifies the Dual-Specificity MAPK Phosphatase INDOLE-3-BUTYRIC ACID-RESPONSE5 (IBR5) as a Novel Regulator of Organ Size in Arabidopsis. AB - Mitogen-activated dual-specificity MAPK phosphatases are important negative regulators in the MAPK signalling pathways responsible for many essential processes in plants. In a screen for mutants with reduced organ size we have identified a mutation in the active site of the dual-specificity MAPK phosphatase indole-3-butyric acid-response5 (IBR5) that we named tinkerbell (tink) due to its small size. Analysis of the tink mutant indicates that IBR5 acts as a novel regulator of organ size that changes the rate of growth in petals and leaves. Organ size and shape regulation by IBR5 acts independently of the KLU growth regulatory pathway. Microarray analysis of tink/ibr5-6 mutants identified a likely role for this phosphatase in male gametophyte development. We show that IBR5 may influence the size and shape of petals through auxin and TCP growth regulatory pathways. PMID- 26147118 TI - Comparing Two Intestinal Porcine Epithelial Cell Lines (IPECs): Morphological Differentiation, Function and Metabolism. AB - The pig shows genetical and physiological resemblance to human, which predestines it as an experimental animal model especially for mucosal physiology. Therefore, the intestinal epithelial cell lines 1 and J2 (IPEC-1, IPEC-J2)--spontaneously immortalised cell lines from the porcine intestine--are important tools for studying intestinal function. A microarray (GeneChip Porcine Genome Array) was performed to compare the genome wide gene expression of IPECs. Different significantly up-regulated pathways were identified, like "lysosome", "pathways in cancer", "regulation of actin cytoskeleton" and "oxidative phosphorylation" in IPEC-J2 in comparison to IPEC-1. On the other hand, "spliceosome", "ribosome", "RNA-degradation" and "tight junction" are significantly down-regulated pathways in IPEC-J2 in comparison to IPEC-1. Examined pathways were followed up by functional analyses. ATP-, oxygen, glucose and lactate-measurement provide evidence for up-regulation of oxidative phosphorylation in IPEC-J2. These cells seem to be more active in their metabolism than IPEC-1 cells due to a significant higher ATP-content as well as a higher O2- and glucose-consumption. The down regulated pathway "ribosome" was followed up by measurement of RNA- and protein content. In summary, IPEC-J2 is a morphologically and functionally more differentiated cell line in comparison to IPEC-1. In addition, IPEC-J2 cells are a preferential tool for in vitro studies with the focus on metabolism. PMID- 26147119 TI - A hybrid tumor with schwannoma-perineurioma-neurofibroma morphology. PMID- 26147120 TI - Comparison of Gene Coexpression Profiles and Construction of Conserved Gene Networks to Find Functional Modules. AB - BACKGROUND: Computational approaches toward gene annotation are a formidable challenge, now that many genome sequences have been determined. Each gene has its own function, but complicated cellular functions are achieved by sets of genes. Therefore, sets of genes with strong functional relationships must be identified. For this purpose, the similarities of gene expression patterns and gene sequences have been separately utilized, although the combined information will provide a better solution. RESULT & DISCUSSION: We propose a new method to find functional modules, by comparing gene coexpression profiles among species. A coexpression pattern is represented as a list of coexpressed genes with each guide gene. We compared two coexpression lists, one from a human guide gene and the other from a homologous mouse gene, and defined a measure to evaluate the similarity between the lists. Based on this coexpression similarity, we detected the highly conserved genes, and constructed human gene networks with conserved coexpression between human and mouse. Some of the tightly coupled genes (modules) showed clear functional enrichment, such as immune system and cell cycle, indicating that our method could identify functionally related genes without any prior knowledge. We also found a few functional modules without any annotations, which may be good candidates for novel functional modules. All of the comparisons are available at the http://v1.coxsimdb.info web database. PMID- 26147122 TI - Impact of oral health problems on the quality of life of preschool children: a case-control study. AB - BACKGROUND: There is a need for investigations into the impact of oral problems on OHRQoL with study designs that offer greater strength of evidence. AIM: To evaluate the impact of dental caries and traumatic dental injury (TDI) on the OHRQoL of Brazilian preschool children. DESIGN: A population-based, matched, case control study was conducted involving 415 children aged 3-5 years enrolled at public and private preschools. The case group (impact on OHRQoL) and control group (no impact on OHRQoL) were matched for age, sex, and monthly household income at a 1 : 4 ratio (83 cases and 332 controls). Impact on OHRQoL was assessed using the B-ECOHIS. Dental caries and TDI were determined through clinical oral examinations. Data analysis involved descriptive statistics and conditional logistic regression analysis (P <= 0.05; 95% CI). RESULTS: The most frequent responses on the B-ECOHIS were 'felt pain' (79.7%) and 'difficulty in eating' (35.0%). The following variables were significantly associated with impact on OHRQoL: caries severity (OR = 12.58; 95% CI: 5.31-29.79) and TDI (OR: 2.11; 95% CI: 1.23-3.62). CONCLUSIONS: Caries severity and TDI impacted the OHRQoL of preschool children. PMID- 26147121 TI - Chronic kidney disease and end-stage renal disease are risk factors for poor outcomes of Clostridium difficile infection: a systematic review and meta analysis. AB - BACKGROUND: The objective of this systematic review and meta-analysis was to assess the clinical outcomes of Clostridium difficile infection (CDI) in patients with chronic kidney diseases (CKD) and end-stage renal disease (ESRD). METHODS: A literature search was performed from inception through February 2015. Studies that reported relative risks, odds ratios or hazard ratios comparing the clinical outcomes of CDI in patients with CKD or ESRD and those without CKD or ESRD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. RESULTS: Nineteen studies (a case-control and 18 cohort studies) with 116,875 patients assessing clinical outcomes of CDI were included in the meta-analysis. Pooled RR of severe or complicated CDI in CKD patients was 1.51 (95% CI: 1.00-2.28). The risk of recurrent CDI is significant higher in patients with a pooled RR of 2.73 (95% CI: 1.36-5.47). The pooled RR of mortality risk of CDI in patients with CKD, ESRD and CKD or ESRD were 1.76 (95% CI: 1.26-2.47), 1.58 (1.37-1.83) and 1.76 (1.32-2.34) respectively. CONCLUSION: This meta-analysis demonstrates poor outcomes of CDI including severe and recurrent CDI in CKD patients. History of CKD and ESRD are both associated with increased mortality risk in patients with CDI. PMID- 26147124 TI - Clinical impact of early bronchoscopy in mechanically ventilated patients with aspiration pneumonia. AB - BACKGROUND AND OBJECTIVE: A handful of studies have reported that bronchoscopies influence the clinical outcome of mechanically ventilated patients with aspiration pneumonia. The purpose of the present study is to elucidate the therapeutic role of early bronchoscopy in patients with aspiration who are mechanically ventilated. METHODS: A retrospective cohort study was conducted via medical record review from 2003 through 2013 in a tertiary hospital. All the diagnoses of pneumonia were supported by the probability of aspiration and consolidation of dependent areas confirmed by computed tomography. Patients who underwent bronchoscopy within 24 h after intubation were categorized as the early bronchoscopy group and the others as the late bronchoscopy group. We compared the demographics, clinical parameters and outcomes between the two groups. RESULTS: Of the 154 patients who were included, the early bronchoscopy group (n = 93) showed significantly lower in-intensive care unit (ICU) mortality and 90-day mortality (in-ICU: 4.9% vs 24.6%; 90-day: 11.8 vs 32.8%) regardless of the initial empirical antibiotics. In addition, their sequential organ failure assessment score on day 7 tended to decrease more rapidly. Among the survivors, patients in the early bronchoscopy group were extubated earlier with a higher success rate, had a shorter length of mechanical ventilation and had a shorter ICU stay. The early bronchoscopy was associated with lower 90-day mortality in multivariate analysis (odds ratio: 0.412; 95% confidence interval: 0.192-0.883). CONCLUSIONS: Early bronchoscopy could benefit the clinical outcomes of mechanically ventilated patients with aspiration pneumonia. PMID- 26147123 TI - Characterization of ST14A Cells for Studying Modulation of Voltage-Gated Calcium Channels. AB - In medium spiny neurons (MSNs) of the striatum, dopamine D2 receptors (D2Rs) specifically inhibit the Ca(v)1.3 subtype of L-type Ca(2+) channels (LTCs). MSNs are heterogeneous in their expression of dopamine receptors making the study of D2R pathways difficult in primary neurons. Here, we employed the ST14A cell line, derived from embryonic striatum and characterized to have properties of MSNs, to study Ca(v)1.3 current and its modulation by neurotransmitters. Round, undifferentiated ST14A cells exhibited little to no endogenous Ca(2+) current while differentiated ST14A cells expressed endogenous Ca(2+) current. Transfection with LTC subunits produced functional Ca(v)1.3 current from round cells, providing a homogeneous model system compared to native MSNs for studying D(2)R pathways. However, neither endogenous nor recombinant Ca(v)1.3 current was modulated by the D(2)R agonist quinpirole. We confirmed D(2)R expression in ST14A cells and also detected D(1)Rs, D(4)Rs, D(5)Rs, G(q), calcineurin and phospholipase A2 using RT-PCR and/or Western blot analysis. Phospholipase C beta 1 (PLCbeta-1) expression was not detected by Western blot analysis which may account for the lack of LTC modulation by D2Rs. These findings raise caution about the assumption that the presence of G-protein coupled receptors in cell lines indicates the presence of complete signaling cascades. However, exogenous arachidonic acid inhibited recombinant Ca(v)1.3 current indicating that channels expressed in ST14A cells are capable of modulation since they respond to a known signaling molecule downstream of D(2)Rs. Thus, ST14A cells provide a MSN-like cell line for studying channel modulation and signaling pathways that do not involve activation of PLCbeta-1. PMID- 26147125 TI - Ordinary Social Interaction and the Main Effect Between Perceived Support and Affect. AB - Relational regulation theory hypothesizes that (a) the main effect between perceived support and mental health primarily reflects ordinary social interaction rather than conversations about stress and how to cope with it, and (b) the extent to which a provider regulates a recipient's mental health primarily reflects the recipient's personal taste (i.e., is relational), rather than the provider's objective supportiveness. In three round-robin studies, participants rated each other on supportiveness and the quality of ordinary social interaction, as well as their own affect when interacting with each other. Samples included marines about to deploy to Afghanistan (N = 100; 150 dyads), students sharing apartments (N = 64; 96 dyads), and strangers (N = 48; 72 dyads). Perceived support and ordinary social interaction were primarily relational, and most of perceived support's main effect on positive affect was redundant with ordinary social interaction. The main effect between perceived support and affect emerged among strangers after brief text conversations, and these links were partially verified by independent observers. Findings for negative affect were less consistent with theory. Ordinary social interaction appears to be able to explain much of the main effect between perceived support and positive affect. PMID- 26147126 TI - Working With Socially and Medically Complex Patients: When Care Transitions Are Circular, Overlapping, and Continual Rather Than Linear and Finite. AB - The care coordination program described here evolved from 5 years of trial and learning related to how to best serve our high-cost, high-utilizing, chronically ill, urban core patient population. In addition to medical complexity, they have daily challenges characteristic of persons served by Safety-Net health systems. Many have unstable health insurance status. Others have insecure housing. A number of patients have a history of substance use and mental illness. Many have fractured social supports. Although some of the best-known care transition models have been successful in reducing rehospitalizations and cost among patients studied, these models were developed for a relatively high functioning patient population with social support. We describe a successful approach targeted at working with patients who require a more intense and lengthy care coordination intervention to self-manage and reduce the cost of caring for their medical conditions. Using a diverse team and a set of replicable processes, we have demonstrated statistically significant reduction in the use of hospital and emergency services. Our intervention leverages the strengths and resilience of patients, focuses on trust and self-management, and targets heterogeneous "high utilizer" patients with medical and social complexity. PMID- 26147127 TI - Remitting seronegative symmetrical synovitis with pitting edema associated with parvovirus B19 infection: two new cases and review of the comorbidities. AB - BACKGROUND: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare syndrome consisting of acute symmetrical tenosynovitis of the hands and wrists associated with pain and marked pitting edema of the dorsum of the hands or the feet. Persistent rheumatoid factor seronegativity and elevated acute phase reactants are the rule, while radiographic findings are characterized by the absence of bony erosions. The syndrome has occasionally been associated with a wide range of diseases including solid and hematological malignancies, polymyalgia rheumatica, and other inflammatory rheumatic diseases. METHODS: Two patients with skin eruption on hands and feet associated with arthromyalgias have been investigated to confirm diagnosis of RS3PE and to detect comorbidities. A revision of all the possible medical conditions correlated to RS3PE has been performed. RESULTS: We report two cases of RS3PE associated with Parvovirus B19 infection/reactivation. There are very few reports on the association between RS3PE and infectious agents, and in only one case the syndrome has been correlated to parvovirus infection. CONCLUSIONS: We want to underline the importance for patients with RS3PE to be seen by dermatologists who should become familiar with this syndrome and remark that Parvovirus B19 infection may be a potential cause of RS3PE. PMID- 26147128 TI - A User-Centered Design Approach to Information Sharing for Older Patients and Their Families. PMID- 26147129 TI - Genetic variation in circadian regulation of nocturnal stomatal conductance enhances carbon assimilation and growth. AB - Circadian resonance, whereby a plant's endogenous rhythms are tuned to match environmental cues, has been repeatedly shown to be adaptive, although the underlying mechanisms remain elusive. Concomitantly, the adaptive value of nocturnal transpiration in C3 plants remains unknown because it occurs without carbon assimilation. These seemingly unrelated processes are interconnected because circadian regulation drives temporal patterns in nocturnal stomatal conductance, with maximum values occurring immediately before dawn for many species. We grew individuals of six Eucalyptus camaldulensis genotypes in naturally lit glasshouses and measured sunset, predawn and midday leaf gas exchange and whole-plant biomass production. We tested whether sunrise anticipation by the circadian clock and subsequent increases in genotype predawn stomatal conductance led to rapid stomatal opening upon illumination, ultimately affecting genotype differences in carbon assimilation and growth. We observed faster stomatal responses to light inputs at sunrise in genotypes with higher predawn stomatal conductance. Moreover, early morning and midday stomatal conductance and carbon assimilation, leaf area and total plant biomass were all positively correlated with predawn stomatal conductance across genotypes. Our results lead to the novel hypothesis that genotypic variation in the circadian regulated capacity to anticipate sunrise could be an important factor underlying intraspecific variation in tree growth. PMID- 26147130 TI - President's Address: International Liver Transplantation Society. PMID- 26147131 TI - South East European Health Network Initiative for Organ Donation and Transplantation. PMID- 26147133 TI - You Are What You Eat: Metabolites of Gut Microbiota Provide Novel Insights into Diagnosis and Development of Chronic Kidney Disease. PMID- 26147134 TI - Flow Cytometry in Transplantation. PMID- 26147135 TI - David K. C. Cooper, MD, PhD: Professor of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, PA. PMID- 26147136 TI - Early Microchimerism After Face Transplantation Detected by Quantitative Real time Polymerase Chain Reaction of Insertion/Deletion Polymorphisms. PMID- 26147137 TI - A Cytomegalovirus-related Pseudotumor in the Colon of A Renal Transplant Recipient Shrunk by Antiviral Therapy. PMID- 26147138 TI - Awaiting Liver Transplantation. PMID- 26147139 TI - Views from academia and industry on skills needed for the modern research environment. AB - Reports from employers of higher education graduates indicate the existence of a considerable gap between the skills required by employers and those possessed by recent graduates. As a first step toward closing this gap, this study aims to determine its origin. Interviews with nine research-active biochemistry professionals were used to identify the most important skills for biochemistry students to succeed in research positions postgraduation. The results of these interviews were used to develop a survey, which was then administered to a larger group of biochemistry faculty and industry professionals. The output of the survey was a list of 52 skills valued by biochemistry professionals and rated by perceived importance. Importantly, the survey results also afford a comparative look at the prioritization of skills by two key populations: the academic faculty training students and the industry professionals hiring them. While there are many areas of agreement between these two populations, the survey also reveals areas were priorities diverge. The discrepancies found here suggest that the skills gap manifest at the point of employment may stem directly from differences in prioritization between the academic and industrial environments. This article aims to provide insight into the needs and requirements of the modern biochemical research environment, and invites debate concerning the preparation students receive in academia. Moreover, the results presented herein point to a need for further exploration of the possible misalignment of these two critical environments for young scientists. PMID- 26147140 TI - Circulating AFABP promotes insulin secretion. PMID- 26147141 TI - Pre-transplant assessment of CMV-specific immune response by Elispot assay in kidney transplant recipients. AB - Cytomegalovirus (CMV) primary infection or re-activation in solid organ transplant (SOT) recipients is associated with increased morbidity and mortality, with patients with IgG-CMV D+/R- sero-matching at greater risk. The impact of pre transplant CMV-specific host cellular immunity on the long-term risk of CMV replication in kidney transplants (KT) was prospectively evaluated in eighty patients by CMV-EliSpot assay. The study population included 54 male and 26 female recipients, with CMV-IgG distribution: 60 D+/R+, 11 D-/R+, 7 D+/R-, 2 D-/R . At pre-transplantation, 49 KT (61.3%) were CMV-responders by EliSpot. At 3 month follow up, 16 (32.7%) out of 49 CMV-responders showed CMV blood infection, compared to 8 (25.8%) out of 31 non-responders. No further episode of CMV viraemia was reported in the responder group, in comparison to 15 out 31 non responders (48.4%) showing at least one episode of CMV-DNAemia at 12-month follow up. Baseline CMV-IgG serology showed a strong correlation with EliSpot determinations; KT recipients exhibiting at least one episode of CMV viraemia at 12-month follow-up showed lower baseline CMV-EliSpot values than those without signs of CMV replication. The study suggests that monitoring CMV-specific T-cell responses at pre-transplantation by EliSpot assay may be useful for predicting the post-transplantation risk of CMV infection and reactivation. PMID- 26147142 TI - Comparison of the artus HIV-1 QS-RGQ and VERSANT HIV-1 RNA 1.0 assays for quantitative detection of human immunodeficiency virus type 1 in plasma samples. AB - Several integrated diagnostic platforms to quantify human immunodeficiency virus type-1 viremia have been developed in recent years. We evaluated the performances of the Artus HIV-1 QS-RGQ assay, using the complete QIAsymphony RGQ workflow. 192 clinical plasma specimens and external control panel samples were analyzed, using the Artus assay and the routine Siemens VERSANT HIV-1 RNA 1.0 assay. Three samples were excluded due to amplification inhibition. Among the remaining 189 specimens, 130 samples were detected as positive (above the limit of detection by both assays; median log10 difference: 0.01) and 18 samples were detected as negative. Eight samples (4.2%), all slightly above the limit of detection of the Versant assay, were negative with the Artus assay. The remaining 33 samples (beside 3 negative by Artus assay) were positive by both assays, but below the limit of detection at least in one of them. Results from the external panel samples showed a mean Log10 variation of -0.18 and -0.45 for the Versant and the Artus assays, respectively. As both assays showed highly correlated results, the QIAsymphony RGQ system, using the Artus HIV-1 QS-RGQ assay, could be considered a potential platform for HIV-1 RNA quantification in plasma. PMID- 26147143 TI - A misleading false-negative result using Neisseria gonorrhoeae opa MGB multiplex PCR assay in patient's rectal sample due to partial mutations of the opa gene. AB - A 53-year-old homosexual man presented at his general practitioner (GP) practice with a suspicion of sexually transmitted infection. Initial NAAT screening was performed for Chlamydia trachomatis and Neisseria gonorrhoeae. The patient was positive for Neisseria gonorrhoeae both for his urine and rectal sample. The subsequent confirmation test for Neisseria gonorrhoeae by a second laboratory was only confirmed for the urine sample and the rectal sample was negative. We report a case of a potential false-negative diagnosis of Neisseria gonorrhoeae due to mutations of DNA sequence in the probe region of opa-MGB assay of the rectal sample. The patient did not suffer any discomfort as diagnosis of Neisseria gonorrhoeae in his urine sample had already led to treatment by prescribing the patient with Ceftriaxone 500 mg IV dissolved in 1 ml lidocaine 2% and 4 mL saline. The patient also received a prescription for Azithromycin (2x500 mg). PMID- 26147144 TI - Calcaneal quantitative ultrasound (QUS) and dual X-ray absorptiometry (DXA) bone analysis in adult HIV-positive patients. AB - Human immunodeficiency virus (HIV)-infected patients have an increased risk of developing osteopenia or osteoporosis compared with healthy individuals. Our aim was to compare dual X-ray absorptiometry (DXA), the gold standard for measuring bone mineral density (BMD), with bone quantitative ultrasound (QUS), an alternative technique for predicting fractures and screening low BMD, at least in postmenopausal populations. We analyzed DXA and QUS parameters to investigate their accuracy in the diagnosis and prediction of bone alterations in a cohort of 224 HIV-1-positive patients. The speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) parameters showed a moderate correlation with DXA, especially with total-body BMD (r coefficient of 0.38, 0.4 and 0.42 respectively), particularly in the female subgroup. In addition, multivariate analysis of HIV-positive patients assessed for vertebral fractures indicated that QUS was more effective than DXA at predicting the risk of fracture. QUS can be used as an additional tool for analyzing bone density in HIV positive patients and its case of use and low cost make it especially suitable for resource-limited settings where DXA is not employed. PMID- 26147145 TI - Neutrophil CD64 expression: a reliable diagnostic marker of infection in advanced cancer patients? AB - Infection and sepsis are major health problems in cancer patients. There is a need for the identification and validation of biomarkers to improve their early diagnosis and treatment. Emerging evidence showed that neutrophil CD64 is a highly sensitive and specific marker for systemic infection and sepsis in critically ill patients with various diseases but data on patients bearing solid tumors are still lacking. Using a dedicated flow cytometric assay we evaluated neutrophil CD64 expression in patients with advanced cancer without active infections to verify if it could be utilized as a reliable biomarker of early infections also in oncologic patients. PMID- 26147146 TI - Application of multiple laboratory tests for Mycobacterium avium ssp. paratuberculosis detection in Crohn's disease patient specimens. AB - The difficulties involved in detecting and enumerating Mycobacterium avium subsp. paratuberculosis (MAP) as a pathogen potentially involved in Crohn's disease (CD) are well known. This study aimed to improve this situation through the application of multiple laboratory diagnostic tests to detect and isolate this bacterium from different specimens collected from CD-patients and non-CD subjects as controls. A total of 120 samples (terminal ileum and colon biopsies, blood and stool) were obtained from 19 CD-patients and from 11 individuals who did not have a clinicopathological diagnosis of CD (non-CD controls) attending for ileocolonoscopy. All samples were processed by staining techniques, culture on both solid and liquid media, and Insertion Sequence 900/F57 real-time PCR. The MAP frequency in CD-patients was found in a significantly greater proportion than in non-CD subjects; the most positive samples were biopsies from CD-patients tested by real-time PCR. MAP detection in biopsies, and in the other samples, by applying multiple and validated laboratory diagnostic tests, could be a marker of active infection, supporting MAP involvement in CD. PMID- 26147147 TI - Antimicrobial resistance and virulence traits in Enterococcus strains isolated from dogs and cats. AB - We investigated presence and prevalence of antibiotic-resistances and other biological characters in enterococci isolated from faeces of healthy dogs and cats because these microorganisms represent important human and veterinary pathogens/opportunists, and a significant burden for healthcare systems. In all samples (n=115) we detected enterococci, with a predominance of Enterococcus faecium (42; 36.5%) and Enterococcus faecalis (36; 31.3%) species, endowed with virulence traits and multidrug-resistance. The two predominant resistance patterns (erythromycin, tetracycline) were examined by polymerase chain reaction for tet and erm genes. Only tetM for tetracycline, and ermA and ermB for erythromycin were detected. PCR for gelatinase gene (gelE) was positive in 62.6% of isolates, but only 26.1% produce gelatinase suggesting the existence of silent genes. efaAfs and efaAfm genes were found in E. faecalis and E. faecium respectively. 89.6% of isolates produced bacteriocin-like substances with a prevailing action against Listeria genus and, among these, 33.9% were positive for the bacteriocin structural genes entA, entL50 or entP. According to our study, pet animals can be considered a reservoir of potentially pathogenic enterococci and we cannot exclude that those microorganisms may be responsible for opportunistic infections in high-risk pet owners. PMID- 26147148 TI - Accuracy of a vancomycin brain heart infusion screening plate for the screening of Staphylococcus aureus isolates with increased vancomycin minimum inhibitory concentrations. AB - Vancomycin susceptibility was determined in 125 S. aureus isolates by disk diffusion, microdilution, Etest and vancomycin brain heart infusion (BHI) plate. A 2.0 mg/L vancomycin BHI was highly sensitive (100% and 91% compared to Etest and microdilution) for detecting a MIC>=2 mg/L, and could be used as a simple and affordable screening test. PMID- 26147149 TI - Turnaround time of positive blood cultures after the introduction of matrix assisted laser desorption-ionization time-of-flight mass spectrometry. AB - A comparative evaluation of the turnaround time (TAT) of positive blood culture before and after matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) introduction in the laboratory routine was performed. A total of 643 positive blood cultures, of which 310 before and 333 after MALDI TOF technique introduction, were collected. In the post MALDI-TOF period, blood culture median TAT decreased from 73.53 hours to 71.73 for Gram-positive, from 64.09 hours to 63.59 for Gram-negative and from 115.7 hours to 47.62 for anaerobes. MALDI-TOF significantly decreased the TAT of anaerobes, for which antimicrobial susceptibility test is not routinely performed. Furthermore, the major advantage of MALDI-TOF introduction was the decrease of the time for pathogen identification (TID) independently from the species with an improvement of 93% for Gram-positive, 86% for Gram-negative and 95% for anaerobes. In addition, high species-level identification rates and cost savings than conventional methods were achieved after MALDI-TOF introduction. PMID- 26147150 TI - Containment of carbapenem resistance rates of Klebsiella pneumoniae and Acinetobacter baumannii in a Greek hospital with a concomitant increase in colistin, gentamicin and tigecycline resistance. AB - In 2010 the Hellenic center for disease control and prevention launched the "Prokroustes" nationwide action plan to tackle the increasing rates of carbapenem resistance among gram-negative nosocomial pathogens. In the present report, data from a Greek tertiary-care hospital are presented three years after the adoption of the infection control measures. Carbapenem resistance rates have been contained for Klebsiella pneumoniae and Acinetobacter baumannii but not for Pseudomonas aeruginosa. More worryingly, in accordance with their overuse against carbapenem-resistant bacteria, resistance rates to colistin and tigecycline have risen significantly. PMID- 26147151 TI - Detection of an IncA/C plasmid encoding VIM-4 and CMY-4 beta-lactamases in Klebsiella oxytoca and Citrobacter koseri from an inpatient in a cardiac rehabilitation unit. AB - A 62-year-old patient was transferred to the cardiac rehabilitation unit of the I.R.C.C.S. Fondazione S. Maugeri after undergoing a heart transplantation at the Acute Care Hospital I.R.C.C.S. S. Matteo of Pavia. On 1 August 2013 and during hospitalization in the rehabilitation unit, Klebsiella oxytoca and Citrobacter koseri clinical isolates were simultaneously recovered from the patient's preputial swab. Both the K. oxytoca and C. koseri strains were carbapenem- resistant by MicroScan System (Beckman Coulter). Carbapenem-resistant K. pneumoniae had previously been reported in the same rehabilitation facility. The aim of the study was to identify the carbapenem resistance mechanisms among the enterobacterial species recovered. Phenotypic screening tests useful to detect the beta-lactamases/carbapenemases were performed. Carbapenem MICs were obtained by Etest. AmpC and MBL encoding genes were identified by PCR and sequencing. Conjugation assays and plasmid characterization were performed. Both of the K. oxytoca and C. koseri isolates were multi drug resistant, showing resistance to amoxicillin-clavulanic acid, three generation cephalosporins, ertapenem (K. oxytoca MIC, >32 mg/L; C. koseri MIC, 4 mg/L), imipenem (K. oxytoca MIC, 4 mg/L; C. koseri MIC, 12 mg/L), thrimethoprim sulphamethoxazole and gentamicin. Susceptibility was retained to fluoroquinolones, colistin and tigecycline. Molecular characterization confirmed the co-presence of blaCMY-4 and blaVIM-4 determinants in a 150 Kb transferable plasmid of IncA/C group. This case is the first detection in Italy of the K. oxytoca and C. koseri clinical isolates co producing the CMY-4 and VIM-4 enzymes. PMID- 26147152 TI - Trichphyton violaceum and T. soudanese: re-emerging pathogens in Italy, 2005 2013. AB - Dermatomycoses due to Trichophyton violaceum are described in Mediterranean Countries, North Africa and in the Horn of Africa where T. soudanense is present too, but it was rare until few years ago in Italy. Aim of the present study was to evaluate an Italian multicenter 9 year (2005-2013) experience concerning these re-emerging pathogens. Fifty three fungal strains were sent from clinical laboratories to the Medical Mycology Committee (CoSM)--Italian Association of Clinical Microbiology (AMCLI) for mycological confirmation. Strains were identified as T. violaceum (23) and T. soudanense (30) by phenotypic and genotypic methods. These dermatophytes present epidemiological (high rate of inter-human transmission, high risk among adopted children coming from countries of either the Horn of Africa or Sub-Saharan Africa also in outbreaks of tinea capitis) and clinical peculiarities (reduced alopecia, presence of exudative lesions) confirming the originality of these "imported" dermatophyte infections. PMID- 26147153 TI - A topical desiccant agent in association with ultrasonic debridement in the initial treatment of chronic periodontitis: a clinical and microbiological study. AB - Effective sub-gingival debridement is crucial to prevent serious systemic infections in hospitalized patients. Lack of compliance and the impracticality of repeated treatment in a short span of time are identified barriers to the performance of full mouth scaling and root planing (SRP). The aim of this randomized study was to evaluate the clinical and microbiological effects of the adjunctive administration of a locally delivered desiccant liquid with molecular hygroscopic properties (HYBENX(r) Oral Tissue DecontaminantTM; HBX) in association with sub-gingival ultrasonic debridement (UD) in a hospital setting. Sixteen patients presenting moderate to severe chronic periodontitis were followed in a randomized 3 month, split mouth, single-blind, prospective study. At baseline (T1) control and test sides were treated with supra and subgingival UD with or without the association of a locally delivered desiccant liquid (HBX). Treatment was repeated after 6 weeks (T2). Clinical and microbiological parameters were assessed at T1, T2 and at 3 months (T3). The test group sites presented a significantly greater reduction in visible plaque index (VPI), bleeding on probing scores (BOP) and gingival index (GI) at T2 and T3 compared to the control group sites. HBX as monotherapy reached the same bacterial load reduction as UD. Compared to UD, a combined HBX-UD treatment resulted in a statistically significant greater bacterial load reduction immediately after treatment. A significantly lower anaerobic bacterial load was still present at T2. Data obtained show that decreased inflammatory signs and reduction of the bacterial load can be obtained in the short term by topical association of the desiccant agent HBX with UD. PMID- 26147155 TI - Synthesis and Suzuki Reactions of N-Heterocyclic Carbene Difluoro(aryl)-boranes. AB - Readily available NHC-arylboranes (NHC-BH2Ar) are converted in high yield to stable NHC-difluoro(aryl)boranes (NHC-BF2Ar) by treatment with 2 equiv of 1 chloromethyl-4-fluoro-1,4-diazonia-bicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor). In turn, the NHC-difluoro(aryl)boranes participate directly in Suzuki reactions under conditions previously used for anionic trifluoroborate salts. Accordingly, NHC-difluoroboranes are a new class of stable precursors for Suzuki reactions. PMID- 26147154 TI - Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. AB - GIFT-I is a phase 3 trial evaluating the efficacy and safety of a 12-week regimen of coformulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) for treatment of Japanese hepatitis C virus genotype 1b-infected patients. It consists of a double-blind, placebo-controlled substudy of patients without cirrhosis and an open-label substudy of patients with compensated cirrhosis. Patients without cirrhosis were randomized 2:1 to once-daily OBV/PTV/r (25 mg/150 mg/100 mg; group A) or placebo (group B). Patients with cirrhosis received open-label OBV/PTV/r (group C). The primary efficacy endpoint was the rate of sustained virological response 12 weeks posttreatment in interferon-eligible, treatment-naive patients without cirrhosis and hepatitis C virus RNA >=100,000 IU/mL in group A. A total of 321 patients without cirrhosis were randomized and dosed with double-blind study drug (106 received double-blind placebo and later received open-label OBV/PTV/r), and 42 patients with cirrhosis were enrolled and dosed with open label OBV/PTV/r. In the primary efficacy population, the rate of sustained virological response 12 weeks posttreatment was 94.6% (106/112, 95% confidence interval 90.5-98.8). Sustained virological response 12 weeks posttreatment rates were 94.9% (204/215) in group A, 98.1% (104/106) in group B (open-label), and 90.5% (38/42) in group C. Overall, virological failure occurred in 3.0% (11/363) of patients who received OBV/PTV/r. The rate of discontinuation due to adverse events was 0%-2.4% in the three patient groups receiving OBV/PTV/r. The most frequent adverse event in patients in any group was nasopharyngitis. CONCLUSION: In this broad hepatitis C virus genotype 1b-infected Japanese patient population with or without cirrhosis, treatment with OBV/PTV/r for 12 weeks was highly effective and demonstrated a favorable safety profile. PMID- 26147156 TI - Land use efficiency: anticipating future demand for land-sector greenhouse gas emissions abatement and managing trade-offs with agriculture, water, and biodiversity. AB - Competition for land is increasing, and policy needs to ensure the efficient supply of multiple ecosystem services from land systems. We modelled the spatially explicit potential future supply of ecosystem services in Australia's intensive agricultural land in response to carbon markets under four global outlooks from 2013 to 2050. We assessed the productive efficiency of greenhouse gas emissions abatement, agricultural production, water resources, and biodiversity services and compared these to production possibility frontiers (PPFs). While interacting commodity markets and carbon markets produced efficient outcomes for agricultural production and emissions abatement, more efficient outcomes were possible for water resources and biodiversity services due to weak price signals. However, when only two objectives were considered as per typical efficiency assessments, efficiency improvements involved significant unintended trade-offs for the other objectives and incurred substantial opportunity costs. Considering multiple objectives simultaneously enabled the identification of land use arrangements that were efficient over multiple ecosystem services. Efficient land use arrangements could be selected that meet society's preferences for ecosystem service provision from land by adjusting the metric used to combine multiple services. To effectively manage competition for land via land use efficiency, market incentives are needed that effectively price multiple ecosystem services. PMID- 26147158 TI - Pastry cream pedagogy: what making macarons taught me about dental practice. PMID- 26147159 TI - Trauma happens: a minimally invasive approach to restoring fractured anterior teeth. PMID- 26147157 TI - Rational Modulation of the Induced-Fit Conformational Change for Slow-Onset Inhibition in Mycobacterium tuberculosis InhA. AB - Slow-onset enzyme inhibitors are the subject of considerable interest as an approach to increasing the potency of pharmaceutical compounds by extending the residence time of the inhibitor on the target (the lifetime of the drug-receptor complex). However, rational modulation of residence time presents significant challenges because it requires additional mechanistic insight, such as the nature of the transition state for postbinding isomerization. Our previous work, based on X-ray crystallography, enzyme kinetics, and molecular dynamics simulation, suggested that the slow step in inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA involves a change in the conformation of the substrate binding loop from an open state in the initial enzyme-inhibitor complex to a closed state in the final enzyme-inhibitor complex. Here, we use multidimensional free energy landscapes for loop isomerization to obtain a computational model for the transition state. The results suggest that slow-onset inhibitors crowd key side chains on helices that slide past each other during isomerization, resulting in a steric clash. The landscapes become significantly flatter when residues involved in the steric clash are replaced with alanine. Importantly, this lower barrier can be increased by rational inhibitor redesign to restore the steric clash. Crystallographic studies and enzyme kinetics confirm the predicted effects on loop structure and flexibility, as well as inhibitor residence time. These loss and regain of function studies validate our mechanistic hypothesis for interactions controlling substrate binding loop isomerization, providing a platform for the future design of inhibitors with longer residence times and better in vivo potency. Similar opportunities for slow-onset inhibition via the same mechanism are identified in other pathogens. PMID- 26147160 TI - A case of cyberbullying. PMID- 26147161 TI - Smile Design 1.0: Learning from our past to meet the current challenge for predictable success. PMID- 26147162 TI - Conservative management of grossly carious mandibular first molar with a hemisection approach: a case report. AB - The term hemisection refers to the removal or separation of a root-with its accompanying crown portion-from a 2-rooted tooth, such as a mandibular molar. A hemisection is considered a conservative treatment option for mandibular molars that would otherwise require extraction. A hemisection of an affected tooth helps to preserve the tooth structure and alveolar bone and is more economical than other treatment options. Therefore, hemisection may be a suitable alternative to extraction and implant therapy and should be discussed with patients during their consideration of treatment options. This case report describes a hemisection procedure in which the grossly carious distal half of an endodontically treated mandibular left first molar was removed. PMID- 26147163 TI - Influence of irrigation protocols on the bond strength of fiber posts cemented with a self-adhesive luting agent 24 hours after endodontic treatment. AB - The aim of this in vitro study was to evaluate the influence of different irrigation protocols on the bond strength, at different root depths, of fiber posts cemented with a self-adhesive cement 24 hours after endodontic treatment. Fifty-six bovine incisor roots were endodontically prepared and separated into 7 groups (n = 8) according to irrigation protocols: group 1, sterile saline (control); group 2, chlorhexidine (CHX) gel 2% and saline; group 3, sodium hypochlorite (NaOCl) 5.25% and saline; group 4, CHX and saline (final irrigation with ethylenediaminetetraacetic acid [EDTA] 17%); group 5, NaOCl and saline (final irrigation with EDTA); group 6, CHX and saline (final irrigation with NaOCl and EDTA); and group 7, NaOCl (final irrigation with CHX and EDTA). No statistically significant difference was found among the groups. Within the limitations of this study, it can be concluded that the different irrigation protocols did not influence the bond strength of self-adhesive resin cement, which presented similar behaviors at the 3 root depths studied. PMID- 26147164 TI - Bond strengths of a self-etching adhesive to dentin surfaces treated with saliva, blood, and different hemostatic agents. AB - The aim of this study was to evaluate the microtensile bond strengths of a self etching adhesive to dentin surfaces after treatment with 4 different hemostatic agents in the presence of saliva and blood. After testing, no significant differences were found between the mean bond strength of Clearfil SE (CSE) Bond resin adhesive to normal dentin and those of CSE to dentin treated with the hemostatic agents ViscoStat Clear, Astringedent, or Astringedent X (P > 0.05). However, the mean bond strength of CSE Bond to dentin treated with Ankaferd Blood Stopper (ABS) was significantly greater than those of the other groups (P < 0.05). Thus, while 3 of the tested hemostatic agents did not have significant effects on the bond strength of composite resin to dentin, ABS increased the bond strength of CSE Bond to dentin. PMID- 26147165 TI - Soft drinks and in vitro dental erosion. AB - The purpose of this investigation was to determine to what extent the in vitro exposure of healthy teeth to various commonly consumed carbonated soft drinks may precipitate dental erosion. Forty-two healthy, extracted, previously unerupted human molars were weighed prior to, during, and after suspension in various sugared and diet or zero-calorie carbonated beverages for 20 days; the specimens were stored at room temperature while being stirred at 275 rpm. The percentage decrease in tooth weight from before to after exposure represented the weight loss due to enamel erosion; values in the experimental groups varied from 3.22% to 44.52% after 20 days' exposure. Data were subjected to analysis of variance and post hoc Scheffe testing at a level of alpha = 0.05. Nonsugared drinks (diet and zero-calorie) as a whole were more erosive than sugared beverages. A significant positive correlation was found between the amount of titratable acid and percentage of tooth erosion, while a significant negative correlation was revealed between the beverage pH and percentage of tooth erosion. No significant correlations were found between calcium or phosphate ion concentrations and the amount of erosion. It appears that enamel erosion is dependent on not only the beverage flow rate, pH, and amount of titratable acid, but also whether the soft drink is of the diet or zero-calorie variety, which reflects the type of artificial sweetener present. PMID- 26147166 TI - Correlation of maxillary anterior tooth width and outer intercanthal distance. AB - The selection of the correct maxillary anterior teeth to establish proper mesiodistal width in a prosthesis is one of the most crucial phases of prosthodontic treatment. The ratio of facial measurements to natural tooth width could be considered a helpful scale. The aim of this study was to explore the relationship between outer intercanthal distance (OICD) and the combined anterior width (CAW) of maxillary teeth. The CAW between the canine distal contacts and the OICD of 100 men and 100 women were measured. Pearson correlation coefficients demonstrated a positive correlation between OICD and CAW. There was no statistically significant difference between the sexes in mean difference between OICD and CAW. Within the limitations of this study, the results suggest that the OICD can be used as a fairly reliable method to determine the CAW for edentulous patients. PMID- 26147167 TI - Relationship between the positions of impacted third molars and the presence of dentigerous cysts. AB - The objective of this study was to assess the association between the histopathological diagnoses of dentigerous cysts and pericoronal follicles and the positions of impacted third molars. The sample comprised 151 cases, diagnosed as dentigerous cysts and pericoronal follicles. Most patients were female (70.9%), white (90.1%), and age 20 years or older (63.6%). Ninety-eight cases (64.9%) were diagnosed as pericoronal follicles and 53 (35.1%) as dentigerous cysts. Teeth that developed dentigerous cysts were predominantly located in the mandible (84.9%), in a mesioangular position (49.1%), and in the 20- to 29-year age group (66.0%). The mandible seems to be the most frequent location of impacted teeth, probably because mandibular tooth eruption is more difficult, as well as dentigerous cysts, probably because the long duration of impaction increases the exposure to inflammatory stimuli and, thus, the potential for formation of dentigerous cysts. The findings also suggest that the incidence of dentigerous cysts tends to increase with age, especially for mandibular teeth in mesioangular positions. PMID- 26147168 TI - Maxillary sinus and success of dental implants: an update. AB - The maxillary sinus augmentation procedure has been gaining more acceptance among dental professionals. The aim of this review article is to provide an update about various aspects of anatomy, physiology, and common pathological conditions of the maxillary sinus and their clinical relevance to the sinus augmentation procedure and subsequent implant placement. PMID- 26147169 TI - Detection of Class II caries on the iPad with Retina Display. AB - With the increasing use of digital radiography, the display parameters of the devices used to view radiographs have become important factors in caries detection. Interest in the use of tablet devices for this application has increased due to their availability, portability, and ease of use. However, to be effective in clinical situations, these portable devices must have displays that perform well under multiple lighting conditions and at different angles. The purpose of this study was to assess the utility of the iPad with Retina Display for the detection of Class II caries under common overhead lighting conditions. The device was used in both standing and angled positions by 5 reviewers, and their diagnoses of caries were compared to the diagnoses the same reviewers made using a thin-film transistor flat-panel display (TFT-FPD) in dim lighting conditions. Histological analysis was used as the gold standard to confirm the presence or absence of caries. In a standing position, the tablet device performed as well as the TFT-FPD. When used in the angled position, the tablet performed slightly worse than the TFT-FPD. The findings suggest that if the user can compensate for overhead glare, the tablet device may perform as well as a calibrated, upright display in a dimly lit room. PMID- 26147170 TI - Ramadan fasting and dental treatment considerations: a review. AB - During the sacred month of Ramadan, Muslims abstain from the consumption of food from dawn until dusk. Extended fasting hours produce changes in the body's metabolism during this period. A majority of the population who fast also restrict themselves from undergoing dental treatments due to a fear of breaking the fast. Even among health professionals, a certain amount of uncertainty prevails about the implications of treating a patient who is fasting. To help clinicians carry out safe and effective treatment without hampering a patient's religious beliefs, the present article focuses on the effect of Ramadan fasting on the body's metabolism and the ramifications for treatment aspects, including medications and dental procedures. PMID- 26147171 TI - Comparison of state dental radiography safety regulations. AB - The aim of this study was to compare and provide an overview of state policies on occupational exposure, dosimetry, collimation, patient protection, and the use of portable handheld X-ray machines in dentistry. State government webpages containing radiation protection rules and regulations were scanned. The contents were compared against current federal regulations established by the Nuclear Regulatory Commission (NRC) and the US Food and Drug Administration (FDA). They were further evaluated in light of current recommendations from the National Council on Radiation Protection & Measurements (NCRP) and the American Dental Association (ADA). Most states' regulations mirror the exposure limits set forth by the NRC and FDA. Nonregulatory recommendations regarding use of dental radiography are periodically put forth by the NCRP and the ADA. State and federal agencies often follow recommendations from these scientific organizations when creating regulations. Clinicians must be aware of their state's radiation protection rules, as variations among states exist. In addition, recommendations published by organizations such as the NCRP and the ADA, while not legally binding, contribute significantly to the reduction of radiation risks for operators and patients alike. PMID- 26147172 TI - Remineralizing agents: effects on acid-softened enamel. AB - This study sought to evaluate whether remineralizing toothpastes can protect acid softened enamel against further erosive episodes. Fifty enamel slabs of bovine teeth with preformed erosion-like lesions were randomly assigned to 1 control and 4 experimental groups (n = 10): group 1, nanohydroxyapatite (nanoHAp) dentifrice; group 2, arginine and calcium carbonate (CaCO3) dentifrice; group 3, potassium nitrate (KNO3) and high-fluoride (F) availability dentifrice; group 4, ordinary fluoridated dentifrice (OFD); and group 5, control (deionized water). Initial hardness measurements were taken after the different treatments were applied. Statistically significant mineral gains of 8.0% and 10.0% were exhibited in groups 1 and 4, respectively. Groups 2 and 3 showed mineral gains of 4.5% and 2.1%, respectively; these were not statistically significant. Group 5 showed mineral loss (-11.8%). A 1-way analysis of variance showed no statistically significant differences in the mean microhardness values among groups. However, there are indications that the nanoHAp and OFD toothpastes may decrease erosive lesions after treatment, while the arginine + CaCO3 and KNO3 + F pastes may prevent the progression of erosive lesions. PMID- 26147173 TI - Clinicopathologic correlation: palatal mass interfering with seating of a maxillary denture. AB - This paper is a clinicopathologic correlation regarding a 61-year-old patient with an ill-fitting maxillary denture. Examination revealed a firm, nontender palatal mass. Descriptions of the clinical findings, work-up, differential diagnosis, histological observations, and diagnosis of the lesion are presented. PMID- 26147174 TI - Review of the peer review process. AB - Discussions of dental law, ethics, and risk management often center around what a dentist should do to reduce the risk that an upset, litigious patient will seek out an attorney to address the problem. There is a very useful option for the dentist and patient to pursue that eliminates the adversarial stance associated with a lawsuit. The peer review resolution process has been shown to be a positive, professional way to end certain dentist-patient confrontations, and the results normally are upheld in most jurisdictions. PMID- 26147175 TI - Adhesive reattachment rehabilitating a nonvital central incisor with a complicated crown-root fracture: 1-year follow-up. AB - Dental trauma requires immediate treatment. However, some conventional treatments (such as an implant and/or partial fixed denture) will not always be immediately possible, due to the patient's age (mainly in pediatric cases) or lack of immediate financial resources. In such situations, the technique of adhesive reattachment plays an important role as a treatment option in the interim. This case report describes the use of adhesive fragment reattachment in the rehabilitation of a maxillary central incisor with a complicated crown-root fracture. A 1-year follow-up affirmed that the adhesive reattachment efficiently resolved the crown-root fracture, allowing for the retention of the tooth structure. This more conservative multidisciplinary approach restored function, esthetics, and self-esteem to the patient, while preserving all bone and gingival architecture for future implant treatment. PMID- 26147176 TI - Effects of the preparation technique and type of material on the penetrability of sealants. AB - The purpose of this in vitro study was to compare the penetration of 2 resin based and 2 glass ionomer sealants into fissures after either conventional or mechanical preparation. All the materials placed in the conventionally prepared and mechanically prepared fissures penetrated the fissures beyond the standard (0.5-mm) reference line used in this study. For 1 glass ionomer sealant, the number of specimens showing complete penetration of sealant was significantly greater (P < 0.05) in mechanically prepared fissures than in conventionally prepared ones. No significant differences were found between mechanically and conventionally prepared fissures for the other sealants. PMID- 26147177 TI - Simple prosthesis for a cancer patient with a segmental mandibulectomy and free fibula flap reconstruction: a clinical report. AB - Tumors of the mandible often necessitate the resection of a major portion of the body of the mandible as well as tissue from the tongue. Resection of the body of the mandible often leads to discontinuity of the mandible, affecting function to a large extent. While the rehabilitation of such defects with free fibula flaps may provide a certain level of stability to the mandible and aid in the prosthetic rehabilitation of these patients, the bulk of these flaps may create difficulties during prosthetic rehabilitation. The economic constraints of patients and/or their fear of implant surgery may also rule out prosthetic rehabilitation with implant-retained prostheses. This case report describes a simple and cost-effective method of prosthetic rehabilitation for a cancer patient who had undergone a segmental mandibulectomy followed by reconstruction with a free fibula flap. PMID- 26147178 TI - Influence of educational materials on the hygiene and utilization habits of denture wearers. AB - The objective of this study was to investigate the influence of educational materials on the denture hygiene and utilization habits of 70 adult volunteers who had been using complete dentures for at least 5 years. On the day they received new dentures, 32 patients were provided with an illustrated leaflet and verbal instructions on oral hygiene and utilization habits, while the remaining 38 participants were advised to continue cleaning and wearing their new dentures as they had their previous dentures. After a 6- to 10-week period, 66 of 70 subjects were interviewed about socioeconomic factors, denture hygiene, and utilization habits. The percentage of patients with a proper denture care routine was low in both groups, suggesting that patients had a tendency not to change old habits. However, statistical analysis showed a positive correlation between receiving instruction and performing denture care in a way that is closer to the recommended method: brushing without toothpaste, using a specific brush; soaking in a sodium hypochlorite solution; and removing the prosthesis at night. Within the limitations of this study, it was concluded that this approach to patient education could be applied to improve the hygiene and utilization habits of denture wearers as well as encourage the correct use of complete dentures. PMID- 26147179 TI - Effects of sex and proficiency in second language processing as revealed by a large-scale fNIRS study of school-aged children. AB - Previous neuroimaging studies in adults have revealed that first and second languages (L1/L2) share similar neural substrates, and that proficiency is a major determinant of the neural organization of L2 in the lexical-semantic and syntactic domains. However, little is known about neural substrates of children in the phonological domain, or about sex differences. Here, we conducted a large scale study (n = 484) of school-aged children using functional near-infrared spectroscopy and a word repetition task, which requires a great extent of phonological processing. We investigated cortical activation during word processing, emphasizing sex differences, to clarify similarities and differences between L1 and L2, and proficiency-related differences during early L2 learning. L1 and L2 shared similar neural substrates with decreased activation in L2 compared to L1 in the posterior superior/middle temporal and angular/supramarginal gyri for both sexes. Significant sex differences were found in cortical activation within language areas during high-frequency word but not during low-frequency word processing. During high-frequency word processing, widely distributed areas including the angular/supramarginal gyri were activated in boys, while more restricted areas, excluding the angular/supramarginal gyri were activated in girls. Significant sex differences were also found in L2 proficiency-related activation: activation significantly increased with proficiency in boys, whereas no proficiency-related differences were found in girls. Importantly, cortical sex differences emerged with proficiency. Based on previous research, the present results indicate that sex differences are acquired or enlarged during language development through different cognitive strategies between sexes, possibly reflecting their different memory functions. PMID- 26147180 TI - Effects of Lactobacillus paracasei 01 fermented milk beverage on protection of intestinal epithelial cell in vitro. AB - BACKGROUND: Intestinal protection is an important function of probiotics. However, there is no evidence that the potential probiotic Lactobacillus paracasei 01 is able to improve intestinal function. In the present study, the protective effect and underlying mechanisms of L. paracasei 01 on intestinal epithelial cell in vitro were investigated. RESULTS: A fermented milk beverage containing L. paracasei 01 at 3 * 10(8) CFU mL(-1) was made from skim milk powder, glucose, sucrose and isomaltooligosaccharide. Results indicated that L. paracasei 01 fermented milk beverage could reduce macromolecule permeability caused by dextran sodium sulfate-induced damage. Besides, 50 mL L(-1) fermented milk beverage with live L. paracasei 01 in the cell medium could increase intestinal epithelial cell Caco-2 growth, decrease lipopolysaccharide/tumor necrosis factor-alpha (TNF-alpha)/interferon-gamma (IFN-gamma)-induced Caco-2 cell death and chemokine CCL-20 production. The protecting mechanisms involve promoting intestinal epithelial cell growth and intestinal epithelial integrity to strengthen the intestinal barrier against chemical and inflammatory stimuli induced damage. Inhibition of inflammatory cytokines and chemokine such as IFN gamma, TNF-alpha and CCL-20 also contributes to the beneficial effects of this product on epithelial function. CONCLUSION: Lactobacillus paracasei 01 fermented milk beverage may be a new functional food with intestinal protecting effects in vitro. PMID- 26147182 TI - Cross-Aldol Reaction of Isatin with Acetone Catalyzed by Leucinol: A Mechanistic Investigation. AB - Comprehensive mechanistic studies on the enantioselective aldol reaction between isatin (1 a) and acetone, catalyzed by L-leucinol (3 a), unraveled that isatin, apart from being a substrate, also plays an active catalytic role. Conversion of the intermediate oxazolidine 4 into the reactive syn-enamine 6, catalyzed by isatin, was identified as the rate-determining step by both the calculations (DeltaG(?) =26.1 kcal mol(-1) for the analogous L-alaninol, 3 b) and the kinetic isotope effect (kH /kD =2.7 observed for the reaction using [D6 ]acetone). The subsequent reaction of the syn-enamine 6 with isatin produces (S)-2 a (calculated DeltaG(?) =11.6 kcal mol(-1) ). The calculations suggest that the overall stereochemistry is controlled by two key events: 1) the isatin-catalyzed formation of the syn-enamine 6, which is thermodynamically favored over its anti rotamer 7 by 2.3 kcal mol(-1) ; and 2) the high preference of the syn-enamine 6 to produce (S)-2 a on reaction with isatin (1 a) rather than its enantiomer (DeltaDeltaG(?) =2.6 kcal mol(-1) ). PMID- 26147181 TI - Identification and management of nonsystematic purchase task data: Toward best practice. AB - Experimental assessments of demand allow the examination of economic phenomena relevant to the etiology, maintenance, and treatment of addiction and other pathologies (e.g., obesity). Although such assessments have historically been resource intensive, development and use of purchase tasks-in which participants purchase 1 or more hypothetical or real commodities across a range of prices-have made data collection more practical and have increased the rate of scientific discovery. However, extraneous sources of variability occasionally produce nonsystematic demand data, in which price exerts either no or inconsistent effects on the purchases of individual participants. Such data increase measurement error, can often not be interpreted in light of research aims, and likely obscure effects of the variable(s) under investigation. Using data from 494 participants, we introduce and evaluate an algorithm (derived from prior methods) for identifying nonsystematic demand data, wherein individual participants' demand functions are judged against 2 general, empirically based assumptions: (a) global, price-dependent reduction in consumption and (b) consistency in purchasing across prices. We also introduce guidelines for handling nonsystematic data, noting some conditions in which excluding such data from primary analyses may be appropriate and others in which doing so may bias conclusions. Adoption of the methods presented here may serve to unify the research literature and facilitate discovery. PMID- 26147183 TI - Directed Self-Assembly of sub-10 nm Particles: Role of Driving Forces and Template Geometry in Packing and Ordering. AB - By comparing the magnitude of forces, a directed self-assembly mechanism has been suggested previously in which immersion capillary is the only driving force responsible for packing and ordering of nanoparticles, which occur only after the meniscus recedes. However, this mechanism is insufficient to explain vacancies formed by directed self-assembly at low particle concentrations. Utilizing experiments, and Monte Carlo and Brownian dynamics simulations, we developed a theoretical model based on a new proposed mechanism. In our proposed mechanism, the competing driving forces controlling the packing and ordering of sub-10 nm particles are (1) the repulsive component of the pair potential and (2) the attractive capillary forces, both of which apply at the contact line. The repulsive force arises from the high particle concentration, and the attractive force is caused by the surface tension at the contact line. Our theoretical model also indicates that the major part of packing and ordering of nanoparticles occurs before the meniscus recedes. Furthermore, utilizing our model, we are able to predict the various self-assembly configurations of particles as their size increases. These results lay out the interplay between driving forces during directed self-assembly, motivating a better template design now that we know the importance and the dominating driving forces in each regime of particle size. PMID- 26147184 TI - A framework for inverse planning of beam-on times for 3D small animal radiotherapy using interactive multi-objective optimisation. AB - Advances in precision small animal radiotherapy hardware enable the delivery of increasingly complicated dose distributions on the millimeter scale. Manual creation and evaluation of treatment plans becomes difficult or even infeasible with an increasing number of degrees of freedom for dose delivery and available image data. The goal of this work is to develop an optimisation model that determines beam-on times for a given beam configuration, and to assess the feasibility and benefits of an automated treatment planning system for small animal radiotherapy. The developed model determines a Pareto optimal solution using operator-defined weights for a multiple-objective treatment planning problem. An interactive approach allows the planner to navigate towards, and to select the Pareto optimal treatment plan that yields the most preferred trade-off of the conflicting objectives. This model was evaluated using four small animal cases based on cone-beam computed tomography images. Resulting treatment plan quality was compared to the quality of manually optimised treatment plans using dose-volume histograms and metrics. Results show that the developed framework is well capable of optimising beam-on times for 3D dose distributions and offers several advantages over manual treatment plan optimisation. For all cases but the simple flank tumour case, a similar amount of time was needed for manual and automated beam-on time optimisation. In this time frame, manual optimisation generates a single treatment plan, while the inverse planning system yields a set of Pareto optimal solutions which provides quantitative insight on the sensitivity of conflicting objectives. Treatment planning automation decreases the dependence on operator experience and allows for the use of class solutions for similar treatment scenarios. This can shorten the time required for treatment planning and therefore increase animal throughput. In addition, this can improve treatment standardisation and comparability of research data within studies and among different institutes. PMID- 26147185 TI - Modulation of Excited State Proton Transfer Dynamics of a Lactim-Lactam Tautomeric System in Different Block Copolymer-Surfactant Aggregates. AB - The proton transfer (PT) process in 1-(2-hydroxy-5-chloro-phenyl)-3,5-dioxo-1H imidazo-[3,4-b]isoindole (ADCL) has been studied in three different copolymer surfactant supramolecular assemblies prepared in aqueous 1% P123 triblock copolymer micellar solution with varying concentrations of surfactants (sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and triton-X-100 (TX 100)). The aim of the present study is to monitor the modulation of the PT process by changing the degree of micellar hydration inside the P123 micelle with the addition of the three different surfactants (two ionic and one non ionic), that is, in P123-surfactant aggregates. Besides, a comparative study has been done with these results with those in water, pure P123 micellar medium and three different surfactants medium. The micropolarity measurement and time-resolved fluorescence anisotropic measurements have been performed to evaluate the binding location of the probe (ADCL) in the three different copolymer-surfactant supramolecular assemblies. It is found that the micropolarity at the binding site of the molecule in the various environments largely influences the PT rate of ADCL. The PT rate is found to be the slowest in the P123 medium and in P123 surfactant aggregates the rate becomes faster as the micropolarity around the binding locations of the molecule in these aggregates is higher in comparison to that in P123 micelle. PMID- 26147186 TI - Development of a fabric phase sorptive extraction with high-performance liquid chromatography and ultraviolet detection method for the analysis of alkyl phenols in environmental samples. AB - A novel analytical method has been developed and validated for the quantification of alkyl phenols in aqueous and soil samples. Fabric phase sorptive extraction, a new sorptive microextraction technique, has been employed for the preconcentration of some endocrine-disruptor alkylphenol molecules, namely, 4 tert-butylphenol, 4-sec-butylphenol, 4-tert-amylphenol, and 4-cumylphenol, followed by high-performance liquid chromatography with ultraviolet detection. Various parameters influencing the fabric phase sorptive extraction performance, namely, extraction time, eluting solvent, elution time and pH of the sample matrix, were optimized. The chromatographic separation was carried out with a mobile phase of acetonitrile/water (60:40 v/v) at an isocratic flow rate of 1.0 mL/min using a reversed-phase C18 column at lambdamax 225 nm. The calibration curves of target analytes were prepared in the concentration range 5-500 ng/mL with good coefficient of determination values (R2 > 0.992). Extraction efficiency values were 74.0, 75.6, 78.0, and 78.3 for 4-tert-butylphenol, 4-sec-butylphenol, 4-tert-amylphenol, and 4-cumylphenol, respectively. The limits of detection range from 0.161 to 0.192 ng/mL. Subsequently, the new fabric phase sorptive extraction with high-performance liquid chromatography and ultraviolet detection was successfully applied for the recovery of alkyl phenols from spiked ground water, river water, and treated water from a sewage treatment plant, and soil and sludge samples. PMID- 26147187 TI - Formation of copper nanoparticles on poly(thymine) through surface-initiated enzymatic polymerization and its application for DNA detection. AB - Poly(thymine) (polyT) and double-stranded DNA (dsDNA) can act as efficient templates for the formation of copper nanoparticles (CuNPs) at a low concentration of CuSO4, and the formed CuNPs emit excellent fluorescence. In this work, we demonstrated a new and facile strategy for the highly sensitive and selective detection of DNA on streptavidin-functionalized magnetic beads (SA-MB) using DNA-templated CuNPs as the fluorescent probe. Target DNA (tDNA) was hybridized with the capture DNA that was immobilized on the surface of SA-MB. Surface initiated enzymatic polymerization (SIEP) was employed as the signal amplification method to generate the polyT at the 3' end of tDNA for the formation of CuNPs. The incorporation of polyT by SIEP resulted in ~35.7 fold signal amplification compared to the dsDNA after hybridization without SIEP. A dose-response curve for detection of DNA was obtained, with a linear dynamic range of 0.1 nM to 10 nM. We showed that this method has a low pM limit of detection (LOD 98.2 pM) and it is also very sensitive to the mismatch type in a specific DNA sequence. In addition, it avoids rigorously controlled temperature, complex synthesis of the fluorescent probe and prelabeling of DNA strands and eliminates the use of sophisticated experimental techniques and equipment. Armed with these intriguing properties, the proposed system could provide an efficient tool for early diagnosis and risk assessment of malignancy. PMID- 26147188 TI - Positive frequency dependence undermines the success of restoration using historical disturbance regimes. AB - Anthropogenic alterations of historical disturbance regimes (e.g. suppressing floods and wildfires) is a primary mechanism by which exotic species can come to dominate native communities. Unfortunately, reinstating historical disturbance regimes to restore native communities has achieved mixed success. The presence of positive frequency dependence (PFD) is commonly invoked to explain why exotic plant invasions are so difficult to eradicate. However, models examining PFD have not considered the effect of reintroducing disturbances. Using a spatially explicit individual-based model, we consider how magnitude and direction of frequency dependence of native and exotic species affects the success of reintroducing disturbances that favour fitness of natives over exotics. Our model illustrates why restoration is difficult; there is a narrow range of parameters that allows for native species to eliminate or coexist with exotics once they have established. Dominance by exotic invaders occurs with moderate initial frequencies of exotic individuals, aggregation of these individuals, or an exotic propagule production advantage. Reintroducing disturbances allows native dominance only when PFD of the exotic is weaker than that of the native species, disturbance intervals are short, and/or exotics are not initially frequent. Our framework provides guidelines for conditions in which the reintroduction of disturbances will effectively restore invaded habitats. PMID- 26147189 TI - Editorial Comment to Current use of active surveillance for localized prostate cancer: A nationwide survey in Japan. PMID- 26147190 TI - Speciation of animal fat: Needs and challenges. AB - The use of pork fat is a concern for Muslims and Jews, who for religious reasons avoid consuming anything that is pig-derived. The use of bovine materials, including beef fat, is prohibited in Hinduism and may also pose a risk of carrying the infectious agent for bovine spongiform encephalopathy. Vegetable oils are sometimes adulterated with animal fat or pork fat with beef fat for economic gain. The development of methods to determine the species origin of fat has therefore become a priority due to the complex and global nature of the food trade, which creates opportunities for the fraudulent use of these animal fats as food ingredients. However, determining the species origin of fats in processed foods or composite blends is an arduous task as the adulterant has a composition that is very similar to that of the original fat or oil. This review examines some of the methods that have been developed for fat speciation, including both fat-based and DNA-based methods, their shortcomings, and the need for additional alternatives. Protein-based methods, specifically immunoassays targeting residual proteins in adipose tissue, that are being explored by researchers as a new tool for fat speciation will also be discussed. PMID- 26147191 TI - Reconfigurable tapered coaxial slot antenna for hepatic microwave ablation. AB - Microwave ablation is rapidly being rediscovered and developed for treating many cancers of liver, lung, kidney and bone, as well as arrhythmias and other medical conditions. The microwaves ablate tissue by heating it to cytotoxic temperatures. The microwave antenna design suffers the challenges of effective coupling and penetration into body tissues, uncontrolled power deposition due to applicator construction limitations affecting uniform heating of target region, and narrowband operation leading to mismatch for many patients and detrimental heating. To meet out the requirements of wideband operation and localized lesion reconfigurable linearly tapered slot interstitial wideband antenna has been proposed for working in the 1.38 GHz to 4.31 GHz frequency band. The performance of the antenna is evaluated by using FEM-based HFSS software. The slot height and taper height are reconfigured for parametric analysis achieving maximum impedance matching and spherical ablation zone without requiring any additional adjustable structures. The tapering of the slot in coaxial antenna generates current distribution at the edges of the slot for maximizing specific absorption rate. PMID- 26147192 TI - Novel FNDC3B and MECOM fusion and WT1 L378fs* 7 frameshift mutation in an acute myeloid leukaemia patient with cytomorphological and immunophenotypic features reminiscent of acute promyelocytic leukaemia. PMID- 26147193 TI - Effect of display location on control-display stereotype strength for translational and rotational controls with linear displays. AB - Experiments were designed to investigate the effects of control type and display location, relative to the operator, on the strength of control/display stereotypes. The Worringham and Beringer Visual Field principle and an extension of this principle for rotary controls (Hoffmann E.R., and Chan A.H.S. 2013). "The Worringham and Beringer 'Visual Field' Principle for Rotary Controls. Ergonomics." 56 (10): 1620-1624) indicated that, for a number of different control types (rotary and lever) on different planes, there should be no significant effect of the display location relative to the seated operator. Past data were surveyed and stereotype strengths listed. Experiments filled gaps where data are not available. Six different control types and seven display locations were used, as in the Frame of Reference Transformation Tool (FORT) model of Wickens et al. (Wickens, C.D., Keller, J.W., and Small, R.L. (2010). "Left. No, Right! Development of the Frame of Reference Transformation Tool (FORT)." Proceedings of the Human Factors and Ergonomics Society 54th Annual Meeting September 2010, 54: 1022-1026). Control/display arrangements with high stereotype strengths were evaluated yielding data for designers of complex control/display arrangements where the control and display are in different planes and for where the operator is moving. It was found possible to predict display/control arrangements with high stereotype strength, based on past data. Practitioner Summary: Controls and displays in complex arrangements need to have high compatibility. These experiments provide arrangements for six different controls (rotary and translational) and seven different display locations relative to the operator. PMID- 26147194 TI - Implicit and Explicit Sexual Attitudes: How Are They Related to Sexual Desire and Sexual Satisfaction in Men and Women? AB - This article examines individual variability in sexual desire and sexual satisfaction by exploring the relation between these sexual aspects and sexual attitudes (implicit and explicit) and by taking gender into account, as this has been shown to be an influential factor. A total of 28 men and 33 women living in heterosexual relationships completed questionnaires assessing sexual desire (dyadic, solitary), sexual satisfaction, and explicit sexual attitudes. An adapted version of the Affect Misattribution Procedure was used to assess implicit sexual attitudes. Results showed higher levels of dyadic and solitary sexual desire in men than in women. No gender differences were found regarding sexual satisfaction or sexual attitudes. High dyadic sexual desire was associated with positive implicit and explicit sexual attitudes, regardless of gender. However, solitary sexual desire was significantly higher in men than women and was associated, in women only, with positive implicit sexual attitudes, suggesting that solitary sexual desire may fulfill different functions in men and women. Finally, sexual satisfaction depended on the combination of explicit and implicit sexual attitudes in both men and women. This study highlights the importance of considering both implicit and explicit sexual attitudes to better understand the mechanisms underlying individual variability in sexual desire and satisfaction. PMID- 26147195 TI - Relationship between tinnitus and suicidal behaviour in Korean men and women: a cross-sectional study. AB - OBJECTIVES: This study investigated the prevalence of suicidal ideation and behaviour in a representative sample of South Koreans with or without tinnitus. DESIGN: A cross-sectional study. SETTING: Based on data from the 2010 to 2012 Korean National Health and Nutrition Examination Survey (KNHANES). PARTICIPANTS: The study included 17 446 Korean individuals. MAIN OUTCOME MEASURES: Participants provided demographic, socio-economic and behavioural information, as well as responses to questionnaires assessing the presence and severity of tinnitus, mental health status regarding stress, depression, and suicidal ideation and attempts. In the univariate analysis, the Rao-Scott chi-square test and logistic regression analysis were used to test the association between tinnitus and risk factors. Simple and multiple linear regression analyses were used to examine the association between tinnitus and mental status. RESULTS: A total of 20.9% and 1.2% of participants with tinnitus, and 12.2% and 0.6% of those without, reported suicidal ideation and attempts, respectively (P < 0.0001 and P = 0.001). Participants reporting suicide attempts showed a higher proportion of severe annoying (6.0%) and irritating (11.8%) tinnitus than those with suicidal ideation (1.4% and 10.2%, respectively). Risks for experiencing tinnitus were significantly associated with suicidal ideation and attempts after adjusting for confounding variables. CONCLUSION: This study has important implications for enhanced screening and evaluation of mental health status and suicidal ideation/behaviour among tinnitus patients. PMID- 26147196 TI - Automated Forensic Animal Family Identification by Nested PCR and Melt Curve Analysis on an Off-the-Shelf Thermocycler Augmented with a Centrifugal Microfluidic Disk Segment. AB - Nested PCR remains a labor-intensive and error-prone biomolecular analysis. Laboratory workflow automation by precise control of minute liquid volumes in centrifugal microfluidic Lab-on-a-Chip systems holds great potential for such applications. However, the majority of these systems require costly custom-made processing devices. Our idea is to augment a standard laboratory device, here a centrifugal real-time PCR thermocycler, with inbuilt liquid handling capabilities for automation. We have developed a microfluidic disk segment enabling an automated nested real-time PCR assay for identification of common European animal groups adapted to forensic standards. For the first time we utilize a novel combination of fluidic elements, including pre-storage of reagents, to automate the assay at constant rotational frequency of an off-the-shelf thermocycler. It provides a universal duplex pre-amplification of short fragments of the mitochondrial 12S rRNA and cytochrome b genes, animal-group-specific main amplifications, and melting curve analysis for differentiation. The system was characterized with respect to assay sensitivity, specificity, risk of cross contamination, and detection of minor components in mixtures. 92.2% of the performed tests were recognized as fluidically failure-free sample handling and used for evaluation. Altogether, augmentation of the standard real-time thermocycler with a self-contained centrifugal microfluidic disk segment resulted in an accelerated and automated analysis reducing hands-on time, and circumventing the risk of contamination associated with regular nested PCR protocols. PMID- 26147199 TI - A Markov Chain Monte Carlo Approach to Estimate AIDS after HIV Infection. AB - The spread of human immunodeficiency virus (HIV) infection and the resulting acquired immune deficiency syndrome (AIDS) is a major health concern in many parts of the world, and mathematical models are commonly applied to understand the spread of the HIV epidemic. To understand the spread of HIV and AIDS cases and their parameters in a given population, it is necessary to develop a theoretical framework that takes into account realistic factors. The current study used this framework to assess the interaction between individuals who developed AIDS after HIV infection and individuals who did not develop AIDS after HIV infection (pre-AIDS). We first investigated how probabilistic parameters affect the model in terms of the HIV and AIDS population over a period of time. We observed that there is a critical threshold parameter, R0, which determines the behavior of the model. If R0 <= 1, there is a unique disease-free equilibrium; if R0 < 1, the disease dies out; and if R0 > 1, the disease-free equilibrium is unstable. We also show how a Markov chain Monte Carlo (MCMC) approach could be used as a supplement to forecast the numbers of reported HIV and AIDS cases. An approach using a Monte Carlo analysis is illustrated to understand the impact of model-based predictions in light of uncertain parameters on the spread of HIV. Finally, to examine this framework and demonstrate how it works, a case study was performed of reported HIV and AIDS cases from an annual data set in Malaysia, and then we compared how these approaches complement each other. We conclude that HIV disease in Malaysia shows epidemic behavior, especially in the context of understanding and predicting emerging cases of HIV and AIDS. PMID- 26147198 TI - Enhanced Sleep Is an Evolutionarily Adaptive Response to Starvation Stress in Drosophila. AB - Animals maximize fitness by modulating sleep and foraging strategies in response to changes in nutrient availability. Wild populations of the fruit fly, Drosophila melanogaster, display highly variable levels of starvation and desiccation resistance that differ in accordance with geographic location, nutrient availability, and evolutionary history. Further, flies potently modulate sleep in response to changes in food availability, and selection for starvation resistance enhances sleep, revealing strong genetic relationships between sleep and nutrient availability. To determine the genetic and evolutionary relationship between sleep and nutrient deprivation, we assessed sleep in flies selected for desiccation or starvation resistance. While starvation resistant flies have higher levels of triglycerides, desiccation resistant flies have enhanced glycogen stores, indicative of distinct physiological adaptations to food or water scarcity. Strikingly, selection for starvation resistance, but not desiccation resistance, leads to increased sleep, indicating that enhanced sleep is not a generalized consequence of higher energy stores. Thermotolerance is not altered in starvation or desiccation resistant flies, providing further evidence for context-specific adaptation to environmental stressors. F2 hybrid flies were generated by crossing starvation selected flies with desiccation selected flies, and the relationship between nutrient deprivation and sleep was examined. Hybrids exhibit a positive correlation between starvation resistance and sleep, while no interaction was detected between desiccation resistance and sleep, revealing that prolonged sleep provides an adaptive response to starvation stress. Therefore, these findings demonstrate context-specific evolution of enhanced sleep in response to chronic food deprivation, and provide a model for understanding the evolutionary relationship between sleep and nutrient availability. PMID- 26147197 TI - Meta-Analysis of Public Microarray Datasets Reveals Voltage-Gated Calcium Gene Signatures in Clinical Cancer Patients. AB - Voltage-gated calcium channels (VGCCs) are well documented to play roles in cell proliferation, migration, and apoptosis; however, whether VGCCs regulate the onset and progression of cancer is still under investigation. The VGCC family consists of five members, which are L-type, N-type, T-type, R-type and P/Q type. To date, no holistic approach has been used to screen VGCC family genes in different types of cancer. We analyzed the transcript expression of VGCCs in clinical cancer tissue samples by accessing ONCOMINE (www.oncomine.org), a web based microarray database, to perform a systematic analysis. Every member of the VGCCs was examined across 21 different types of cancer by comparing mRNA expression in cancer to that in normal tissue. A previous study showed that altered expression of mRNA in cancer tissue may play an oncogenic role and promote tumor development; therefore, in the present findings, we focus only on the overexpression of VGCCs in different types of cancer. This bioinformatics analysis revealed that different subtypes of VGCCs (CACNA1C, CACNA1D, CACNA1B, CACNA1G, and CACNA1I) are implicated in the development and progression of diverse types of cancer and show dramatic up-regulation in breast cancer. CACNA1F only showed high expression in testis cancer, whereas CACNA1A, CACNA1C, and CACNA1D were highly expressed in most types of cancer. The current analysis revealed that specific VGCCs likely play essential roles in specific types of cancer. Collectively, we identified several VGCC targets and classified them according to different cancer subtypes for prospective studies on the underlying carcinogenic mechanisms. The present findings suggest that VGCCs are possible targets for prospective investigation in cancer treatment. PMID- 26147200 TI - Who Is He? Children with ASD and ADHD Take the Listener into Account in Their Production of Ambiguous Pronouns. AB - During conversation, speakers constantly make choices about how specific they wish to be in their use of referring expressions. In the present study we investigate whether speakers take the listener into account or whether they base their referential choices solely on their own representation of the discourse. We do this by examining the cognitive mechanisms that underlie the choice of referring expression at different discourse moments. Furthermore, we provide insights into how children with Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) use referring expressions and whether their use differs from that of typically developing (TD) children. Children between 6 and 12 years old (ASD: n=46; ADHD: n=37; TD: n=38) were tested on their production of referring expressions and on Theory of Mind, response inhibition and working memory. We found support for the view that speakers take the listener into account when choosing a referring expression: Theory of Mind was related to referential choice only at those moments when speakers could not solely base their choice on their own discourse representation to be understood. Working memory appeared to be involved in keeping track of the different referents in the discourse. Furthermore, we found that TD children as well as children with ASD and children with ADHD took the listener into account in their choice of referring expression. In addition, children with ADHD were less specific than TD children in contexts with more than one referent. The previously observed problems with referential choice in children with ASD may lie in difficulties in keeping track of longer and more complex discourses, rather than in problems with taking into account the listener. PMID- 26147201 TI - Comprehensive Evaluation of Nuclear Factor-kappaBeta Expression Patterns in Non Small Cell Lung Cancer. AB - Nuclear factor (NF)-kappaB signalling is required for lung adenocarcinoma development in mice, and both of its subunits RelA and RelB were independently reported to be highly expressed in human non-small cell lung cancer (NSCLC). To comprehensively examine NF-kappaB expression in NSCLC, we analyzed serial sections of primary tumor samples from 77 well-documented patients (36 adenocarcinomas, 40 squamous cell carcinomas and 3 large cell carcinomas) for immunoreactivity of RelA, RelB, P50, and P52/P100. Tumor and intratumoral stroma areas were discriminated based on proliferating cell nuclear antigen immunoreactivity and inflammatory infiltration was assessed in intratumoral stroma areas. NF-kappaB immunoreactivity was quantified by intensity, extent, and nuclear localization and was cross-examined with tumor cell proliferation, inflammatory infiltration, and clinical-pathologic data. We found that the expression of the different NF-kappaB subunits was not concordant, warranting our integral approach. Overall, RelA, RelB, and P50 were expressed at higher levels compared with P52/P100. However, RelA and P50 were predominantly expressed in intratumoral stroma, but RelB in tumor cells. Importantly, tumor area RelA expression was correlated with the intensity of inflammatory infiltration, whereas RelB expression was identified in proliferating tumor cells. Using multiple logistic regression, we identified that tumor RelB expression was an independent predictor of lymph node metastasis, and tumor P50 was an independent predictor of TNM6 stage IIB or higher, whereas tumor RelA was an independent predictor of inflammatory infiltration. We conclude that pathologic studies of NF kappaB expression in cancer should include multiple pathway components. Utilizing such an approach, we identified intriguing associations between distinct NF kappaB subunits and clinical and pathologic features of NSCLC. PMID- 26147202 TI - The Light Wavelength Affects the Ontogeny of Clock Gene Expression and Activity Rhythms in Zebrafish Larvae. AB - Light plays a key role in synchronizing rhythms and setting the phase of early development. However, to date, little is known about the impact of light wavelengths during the ontogeny of the molecular clock and the behavioural rhythmicity. The aim of this research was to determine the effect of light of different wavelengths (white, blue and red) on the onset of locomotor activity and clock gene (per1b, per2, clock1, bmal1 and dbp) expression rhythms. For this purpose, 4 groups of zebrafish embryo/larvae were raised from 0 to 7 days post fertilization (dpf) under the following lighting conditions: three groups maintained under light:dark (LD) cycles with white (full visible spectrum, LDW), blue (LDB), or red light (LDR), and one group raised under constant darkness (DD). The results showed that lighting conditions influenced activity rhythms. Larvae were arrhythmic under DD, while under LD cycles they developed wavelength dependent daily activity rhythms which appeared earlier under LDB (4 dpf) than under LDW or LDR (5 dpf). The results also revealed that development and lighting conditions influenced clock gene expression. While clock1 rhythmic expression appeared in all lighting conditions at 7 dpf, per1b, per2 and dbp showed daily variations already at 3 dpf. Curiously, bmal1 showed consistent rhythmic expression from embryonic stage (0 dpf). Summarizing, the data revealed that daily rhythms appeared earlier in the larvae reared under LDB than in those reared under LDW and LDR. These results emphasize the importance of lighting conditions and wavelengths during early development for the ontogeny of daily rhythms of gene expression and how these rhythms are reflected on the behavioural rhythmicity of zebrafish larvae. PMID- 26147203 TI - Effects of Local Habitat Variation on the Behavioral Ecology of Two Sympatric Groups of Brown Howler Monkey (Alouatta clamitans). AB - Although the brown howler monkey (Alouatta clamitans) is a relatively well studied Neotropical primate, its behavioral and dietary flexibility at the intra population level remains poorly documented. This study presents data collected on the behavior and ecology of two closely located groups of brown howlers during the same period at the RPPN Feliciano Miguel Abdala in southeastern Brazil. One group occupied a primary valley habitat, henceforth the Valley Group (VG), and the other group occupied a regenerating hillside habitat, the Hill Group (HG). We hypothesized differences in the behavior and ecological parameters between these sympatric groups due to the predicted harsher conditions on the hillside, compared to the valley. We measured several habitat parameters within the home range of both groups and collected data on the activity budget, diet and day range lengths, from August to November 2005, between dawn and dusk. In total, behavioral data were collected for 26 (318 h) and 28 (308 h) sampling days for VG and HG, respectively. As we predicted, HG spent significantly more time feeding and consumed less fruit and more leaves than VG, consistent with our finding that the hillside habitat was of lower quality. However, HG also spent less time resting and more time travelling than VG, suggesting that the monkeys had to expend more time and energy to obtain high-energy foods, such as fruits and flowers that were more widely spaced in their hill habitat. Our results revealed that different locations in this forest vary in quality and raise the question of how different groups secure their home ranges. Fine-grained comparisons such as this are important to prioritize conservation and management areas within a reserve. PMID- 26147204 TI - Mesenteric Lymphatic-Perilymphatic Adipose Crosstalk: Role in Alcohol-Induced Perilymphatic Adipose Tissue Inflammation. AB - BACKGROUND: The digestive tract lymphatics transport approximately two-thirds of all lymph produced in the body and have a key role in mucosal immunity through their contribution to antigen transport and immune cell trafficking. Mesenteric lymphatic pumping function integrity is critical for maintaining homeostasis and lipid transport. We previously demonstrated that acute alcohol intoxication (AAI) increases mesenteric lymphatic amplitude of contraction and ejection fraction, enhancing the ability of the lymphatic vessels to pump lymph. AAI has been shown to disrupt intestinal barrier integrity, which would be expected to increase the endotoxin content of mesenteric lymph. In this study, we tested the prediction that AAI increases lymphatic permeability directly affecting perilymphatic adipose tissue (PLAT) milieu. METHODS: Male Sprague Dawley rats received an intragastric infusion of 2.5 g/kg of alcohol. Isovolumic administration of water (vehicle) served as control. PLAT was isolated for the determination of Evans Blue extravasation (permeability), cytokine content, and immunohistochemistry for inflammatory cell infiltration at 30 minutes and 24 hours after alcohol administration. RESULTS: PLAT isolated from AAI animals had greater Evans Blue concentrations and cytokine expression (24 hours post-AAI) and mast cell and neutrophil density than that isolated from controls. AAI resulted in significantly higher plasma lipopolysaccharide (endotoxin) levels, lower plasma adiponectin levels (at 30 minutes), and unchanged plasma visfatin levels. CONCLUSIONS: The data indicate that AAI induces mesenteric lymphatic hyperpermeability, promotes PLAT inflammatory milieu and disrupts the systemic adipokine profile. These findings suggest an association between alcohol-induced lymphatic hyperpermeability and early manifestations of metabolic dysfunction as a result of alcohol abuse. We propose that crosstalk between lymph and PLAT results in adipose inflammation and adipokine dysregulation during AAI. PMID- 26147205 TI - Measuring Asymmetry in Time-Stamped Phylogenies. AB - Previous work has shown that asymmetry in viral phylogenies may be indicative of heterogeneity in transmission, for example due to acute HIV infection or the presence of 'core groups' with higher contact rates. Hence, evidence of asymmetry may provide clues to underlying population structure, even when direct information on, for example, stage of infection or contact rates, are missing. However, current tests of phylogenetic asymmetry (a) suffer from false positives when the tips of the phylogeny are sampled at different times and (b) only test for global asymmetry, and hence suffer from false negatives when asymmetry is localised to part of a phylogeny. We present a simple permutation-based approach for testing for asymmetry in a phylogeny, where we compare the observed phylogeny with random phylogenies with the same sampling and coalescence times, to reduce the false positive rate. We also demonstrate how profiles of measures of asymmetry calculated over a range of evolutionary times in the phylogeny can be used to identify local asymmetry. In combination with different metrics of asymmetry, this combined approach offers detailed insights of how phylogenies reconstructed from real viral datasets may deviate from the simplistic assumptions of commonly used coalescent and birth-death process models. PMID- 26147206 TI - Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate--Tackling the Cocktail Challenge. AB - Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 MUg/ml), the blood stage (40-60 MUg/ml) and the sexual stage (1.75 MUg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy. PMID- 26147207 TI - Chemotherapy-driven dysbiosis in the intestinal microbiome. AB - BACKGROUND: Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome. AIM: To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy. METHODS: We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics. RESULTS: We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes (P = 0.0002) and Actinobacteria (P = 0.002) and significant increases in abundances of Proteobacteria (P = 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism (P = 0.0001), energy metabolism (P = 0.001), metabolism of cofactors and vitamins (P = 0.006), and increased capacity for glycan metabolism (P = 0.0002), signal transduction (P = 0.0002) and xenobiotics biodegradation (P = 0.002). CONCLUSIONS: Our study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy-induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome-targeted interventions in cancer patients. PMID- 26147208 TI - Multilevel Analysis of the Predictors of HIV Prevalence among Pregnant Women Enrolled in Annual HIV Sentinel Surveillance in Four States in Southern India. AB - BACKGROUND: Heterogeneity of the HIV epidemic across districts of south India is reflected in HIV positivity among antenatal clinic (ANC) attendees. Along with individual factors, contextual factors also need consideration for effective HIV interventions. Thus, identifying district and individual level factors that influence ANC HIV positivity assumes importance to intervene effectively. METHODS: Data on HIV sentinel surveillance among the ANC population were obtained from the National AIDS Control Organization (NACO) between years 2004 and 2007. Data from serial cross-sectional studies among female sex workers (FSWs) conducted during this time period in 24 districts were used to generate district level variables corresponding to parameters concerning this high risk population. Other district level data were obtained from various official/governmental agencies. Multilevel logistic regression was used to identify individual and district level factors associated with ANC-HIV positivity. RESULTS: The average ANC-HIV prevalence from 2004 to 2007 in the 24 integrated biological and behavioural assessments (IBBA) districts ranged from 0.25 to 3.25%. HIV positivity was significantly higher among ANC women with age >= 25 years [adjusted odds ratio (AOR):1.49; 95% confidence interval (95%CI):1.27 to 1.76] compared to those with age<25 years; illiterate (AOR:1.62; 95%CI:1.03 to 2.54) compared to literate; employed in agriculture (AOR:1.34; 95%CI:1.11 to 1.62) or with occupations like driver/helper/industry/factory workers/hotel staff (AOR:1.59; 95%CI:1.26 to 2.01) compared to unemployed. District level HIV prevalence among FSWs (AOR:1.03; 95%CI:1.0 to 1.05) and percentage women marrying under 18 years were significantly associated with ANC-HIV positivity (AOR:1.02; 95%CI:1.00 to 1.04). CONCLUSION: Illiteracy of the woman, higher HIV prevalence among FSWs and early marriage were associated with HIV positivity among pregnant women in southern India. In addition to targeted HIV preventive interventions among FSWs, studying and changing the behavior of FSW clients and addressing structural drivers of the epidemic might indirectly help reduce HIV infection among women in southern India. PMID- 26147210 TI - The impact of vaginal delivery on pelvic floor function - delivery as a time point for secondary prevention. PMID- 26147209 TI - Phytoene Desaturase from Oryza sativa: Oligomeric Assembly, Membrane Association and Preliminary 3D-Analysis. AB - Recombinant phytoene desaturase (PDS-His6) from rice was purified to near homogeneity and shown to be enzymatically active in a biphasic, liposome-based assay system. The protein contains FAD as the sole protein-bound redox-cofactor. Benzoquinones, not replaceable by molecular oxygen, serve as a final electron acceptor defining PDS as a 15-cis-phytoene (donor):plastoquinone oxidoreductase. The herbicidal PDS-inhibitor norflurazon is capable of arresting the reaction by stabilizing the intermediary FAD(red), while an excess of the quinone acceptor relieves this blockage, indicating competition. The enzyme requires its homo oligomeric association for activity. The sum of data collected through gel permeation chromatography, non-denaturing polyacrylamide electrophoresis, chemical cross-linking, mass spectrometry and electron microscopy techniques indicate that the high-order oligomers formed in solution are the basis for an active preparation. Of these, a tetramer consisting of dimers represents the active unit. This is corroborated by our preliminary X-ray structural analysis that also revealed similarities of the protein fold with the sequence inhomologous bacterial phytoene desaturase CRTI and other oxidoreductases of the GR2-family of flavoproteins. This points to an evolutionary relatedness of CRTI and PDS yielding different carotene desaturation sequences based on homologous protein folds. PMID- 26147211 TI - Correction: The Mechanism of Environmental Endocrine Disruptors (DEHP) Induces Epigenetic Transgenerational Inheritance of Cryptorchidism. PMID- 26147212 TI - Optimization of Molecular Approaches to Genogroup Neisseria meningitidis Carriage Isolates and Implications for Monitoring the Impact of New Serogroup B Vaccines. AB - The reservoir for Neisseria meningitidis (Nm) is the human oropharynx. Implementation of Nm serogroup C (NmC) glycoconjugate vaccines directly reduced NmC carriage. Prophylactic vaccines are now available to prevent disease caused by the five major Nm disease causing serogroups (ABCWY). Nm serogroup B (NmB) vaccines are composed of antigens that are conserved across Nm serogroups and therefore have the potential to impact all Nm carriage. To assess the effect of these vaccines on carriage, standardized approaches to identify and group Nm are required. Real-time PCR (rt-PCR) capsule grouping assays that were internally controlled to confirm Nm species were developed for eight serogroups associated with carriage (A, B, C, E, W, X, Y and Z). The grouping scheme was validated using diverse bacterial species associated with carriage and then used to evaluate a collection of diverse Nm carriage isolates (n=234). A scheme that also included porA and ctrA probes was able to speciate the isolates, while ctrA also provided insights on the integrity of the polysaccharide loci. Isolates were typed for the Nm vaccine antigen factor H binding protein (fHbp), and were found to represent the known diversity of this antigen. The porA rt-PCR yielded positive results with all 234 of the Nm carriage isolates. Genogrouping assays classified 76.5% (179/234) of these isolates to a group, categorized 53 as nongenogroupable (NGG) and two as mixed results. Thirty seven NGG isolates evidenced a disrupted capsular polysaccharide operon judged by a ctrA negative result. Only 28.6% (67/234) of the isolates were serogrouped by slide agglutination (SASG), highlighting the reduced capability of carriage strains to express capsular polysaccharide. These rt-PCR assays provide a comprehensive means to identify and genogroup N. meningitidis in carriage studies used to guide vaccination strategies and to assess the impact of novel fHbp containing vaccines on meningococcal carriage. PMID- 26147214 TI - Dental findings in Brazilian patients with Fanconi syndrome. AB - BACKGROUND: Fanconi syndrome (FS) is a generalized dysfunction of renal proximal tubules resulting in impaired reabsorption of amino acids, phosphate, urate, bicarbonate, glucose, and electrolytes. FS can be a primary renal impairment due to genetic origin or secondary to inborn errors of metabolism or systemic diseases. Main clinical findings are polyuria, failure to thrive, rickets/osteomalacia, metabolic acidosis, bone deformities, and, occasionally, nephrocalcinosis. Although dental abnormalities have been reported in patients with tubulopathies, oral manifestations in FS were very rarely described. CASE REPORT: Two patients with FS exhibiting important dental alterations were reported. Oral examination of the first patient revealed teeth with rough surfaces and white opaque areas. Early loss of primary teeth and delayed eruption of permanent teeth were also observed. Oral examination of the second patient detected delayed eruption of permanent teeth and X-ray images revealed loss of contrast between enamel and dentin. In both patients with FS, loss of bone density in maxilla and mandible was observed in X-ray images. CONCLUSIONS: This study is the first report of dental abnormalities in Brazilian patients with FS. Furthermore, our findings support the general idea that renal tubular disorders might impact on mineralized tissues of the oral cavity. PMID- 26147213 TI - The potential role of sodium glucose co-transporter 2 inhibitors in the early treatment of type 2 diabetes mellitus. AB - BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of pharmacologic agents developed for the treatment of type 2 diabetes mellitus (T2DM). Their unique mechanism of action is independent of pancreatic beta-cell function or the degree of insulin resistance, giving these agents the potential for use in combination with any of the existing classes of glucose-lowering agents, including insulin. This makes SGLT2 inhibitors an option for patients with long-standing T2DM, but they also have a promising role for early intervention in T2DM, and that role is explored in this review. METHODS: A literature search was performed to identify relevant English language articles relating to SGLT2 inhibitors, particularly dapagliflozin, canagliflozin and empagliflozin. RESULTS: Clinical trials of dapagliflozin, canagliflozin and empagliflozin, given as monotherapy or in combination with other glucose-lowering agents, reported clinically significant improvements in glycaemic control, body weight and systolic blood pressure. SGLT2 inhibitors were well tolerated and had a generally favourable safety profile. Few serious adverse events have been reported to date. The frequency of hypoglycaemic events was low, similar to that of placebo, and the choice of co-administered glucose-lowering agent was the major determinant of hypoglycaemic risk. Increased genital and urinary tract infections were consistently reported with SGLT2 inhibitors. CONCLUSIONS: SGLT2 inhibitors, with their unique insulin-independent mode of action, could have a significant impact on the early management of T2DM, by addressing some of the specific risk factors associated with this disease. SGLT2 inhibitors induce beneficial changes in a number of cardiovascular risk factors, such as lowering blood pressure and body weight, in addition to improved glycaemic control, although information on clinical cardiovascular outcomes is currently limited. PMID- 26147215 TI - Patterns of Freshwater Species Richness, Endemism, and Vulnerability in California. AB - The ranges and abundances of species that depend on freshwater habitats are declining worldwide. Efforts to counteract those trends are often hampered by a lack of information about species distribution and conservation status and are often strongly biased toward a few well-studied groups. We identified the 3,906 vascular plants, macroinvertebrates, and vertebrates native to California, USA, that depend on fresh water for at least one stage of their life history. We evaluated the conservation status for these taxa using existing government and non-governmental organization assessments (e.g., endangered species act, NatureServe), created a spatial database of locality observations or distribution information from ~400 data sources, and mapped patterns of richness, endemism, and vulnerability. Although nearly half of all taxa with conservation status (n = 1,939) are vulnerable to extinction, only 114 (6%) of those vulnerable taxa have a legal mandate for protection in the form of formal inclusion on a state or federal endangered species list. Endemic taxa are at greater risk than non endemics, with 90% of the 927 endemic taxa vulnerable to extinction. Records with spatial data were available for a total of 2,276 species (61%). The patterns of species richness differ depending on the taxonomic group analyzed, but are similar across taxonomic level. No particular taxonomic group represents an umbrella for all species, but hotspots of high richness for listed species cover 40% of the hotspots for all other species and 58% of the hotspots for vulnerable freshwater species. By mapping freshwater species hotspots we show locations that represent the top priority for conservation action in the state. This study identifies opportunities to fill gaps in the evaluation of conservation status for freshwater taxa in California, to address the lack of occurrence information for nearly 40% of freshwater taxa and nearly 40% of watersheds in the state, and to implement adequate protections for freshwater taxa where they are currently lacking. PMID- 26147216 TI - Treating fibrosing cholestatic hepatitis C with sofosbuvir and ribavirin: a matched analysis. AB - BACKGROUND: Fibrosing cholestatic hepatitis (FCH) is an uncommon but potentially fatal complication of recurrent hepatitis C (HCV) in liver transplant recipients. METHODS: We matched the treatment outcomes of 10 liver transplant recipients who developed FCH with those of 10 recipients with recurrent HCV without FCH treated with sofosbuvir and ribavirin. RESULTS: Baseline mean alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 186 U/L, 197 U/L, 243 U/L, and 6.7 mg/dL, respectively, in the FCH recipients and 82 U/L, 60 U/L, 110 U/L, and 0.99 mg/dL, respectively, in non-FCH recipients. The sustained viral response in FCH and non-FCH recipients was 40% and 80%, respectively. One-yr patient and graft survival rates were 90% and 80%, respectively, in FCH recipients, and 100% in non-FCH recipients. Seven FCH and six non-FCH recipients were treated for anemia with blood transfusion and/or erythropoietin growth factors. CONCLUSION: Our results suggest that the use of sofosbuvir and ribavirin is effective and tolerable in liver transplant recipients treated for recurrent FCH. There is a trend of lower sustained viral response, patient survival, and graft survival in the FCH recipients. PMID- 26147217 TI - Interactions between histamine H1 receptor and its antagonists by using cell membrane chromatography method. AB - OBJECTIVES: A high histamine H1 receptor (H1 R) expression cell membrane chromatography (CMC) method was developed to investigate the affinity of ligands for H1 R. METHODS: The affinity of ligands for H1 R was evaluated by frontal analysis. Competition studies and molecular docking study were utilized to study the interactions that occurred at specific binding sites on H1 R. KEY FINDINGS: The KD values measured by frontal analysis were (8.72 +/- 0.21) * 10(-7) M for azelastine, (9.12 +/- 0.26) * 10(-7) M for cyproheptadine, (9.90 +/- 0.18) * 10( 7) M for doxepin, (1.42 +/- 0.13) * 10(-6) M for astemizole, (2.25 +/- 0.36) * 10(-6) M for chlorpheniramine and (3.10 +/- 0.27) * 10(-6) M for diphenhydramine. The results had a positive correlation with those from radioligand binding assay. The ability of displacement order measured on the binding sites occupied by doxepin was doxepin (KD , (2.95 +/- 0.21) * 10(-8) M) > astemizole (KD , (5.03 +/- 0.18) * 10(-7) M) > chlorpheniramine (KD , (1.27 +/ 0.16) * 10(-6) M) > cyproheptadine (KD , (1.61 +/- 0.27) * 10(-6) M), whose order met with the scores by molecular docking study. CONCLUSIONS: The studies showed CMC could be applied to investigate drug-receptor interactions. PMID- 26147218 TI - Comparative Genomic Analyses of Multiple Pseudomonas Strains Infecting Corylus avellana Trees Reveal the Occurrence of Two Genetic Clusters with Both Common and Distinctive Virulence and Fitness Traits. AB - The European hazelnut (Corylus avellana) is threatened in Europe by several pseudomonads which cause symptoms ranging from twig dieback to tree death. A comparison of the draft genomes of nine Pseudomonas strains isolated from symptomatic C. avellana trees was performed to identify common and distinctive genomic traits. The thorough assessment of genetic relationships among the strains revealed two clearly distinct clusters: P. avellanae and P. syringae. The latter including the pathovars avellanae, coryli and syringae. Between these two clusters, no recombination event was found. A genomic island of approximately 20 kb, containing the hrp/hrc type III secretion system gene cluster, was found to be present without any genomic difference in all nine pseudomonads. The type III secretion system effector repertoires were remarkably different in the two groups, with P. avellanae showing a higher number of effectors. Homologue genes of the antimetabolite mangotoxin and ice nucleation activity clusters were found solely in all P. syringae pathovar strains, whereas the siderophore yersiniabactin was only present in P. avellanae. All nine strains have genes coding for pectic enzymes and sucrose metabolism. By contrast, they do not have genes coding for indolacetic acid and anti-insect toxin. Collectively, this study reveals that genomically different Pseudomonas can converge on the same host plant by suppressing the host defence mechanisms with the use of different virulence weapons. The integration into their genomes of a horizontally acquired genomic island could play a fundamental role in their evolution, perhaps giving them the ability to exploit new ecological niches. PMID- 26147220 TI - FOXP3 transcription is enhanced in lesional and perilesional skin of patients with focal Alopecia areata. PMID- 26147219 TI - Ubiquitous Over-Expression of Chromatin Remodeling Factor SRG3 Ameliorates the T Cell-Mediated Exacerbation of EAE by Modulating the Phenotypes of both Dendritic Cells and Macrophages. AB - Although SWI3-related gene (SRG3), a chromatin remodeling factor, is critical for various biological processes including early embryogenesis and thymocyte development, it is unclear whether SRG3 is involved in the differentiation of CD4+ T cells, the key mediator of adaptive immune responses. Because it is known that experimental autoimmune encephalomyelitis (EAE) development is determined by the activation of CD4+ T helper cells, here, we investigated the role of SRG3 in EAE development using SRG3 transgenic mouse models exhibiting two distinct SRG3 expression patterns: SRG3 expression driven by either the CD2 or beta-actin promoter. We found that the outcome of EAE development was completely different depending on the expression pattern of SRG3. The specific over-expression of SRG3 using the CD2 promoter facilitated EAE via the induction of Th1 and Th17 cells, whereas the ubiquitous over-expression of SRG3 using the beta-actin promoter inhibited EAE by promoting Th2 differentiation and suppressing Th1 and Th17 differentiation. In addition, the ubiquitous over-expression of SRG3 polarized CD4+ T cell differentiation towards the Th2 phenotype by converting dendritic cells (DCs) or macrophages to Th2 types. SRG3 over-expression not only reduced pro-inflammatory cytokine production by DCs but also shifted macrophages from the inducible nitric oxide synthase (iNOS)-expressing M1 phenotype to the arginase-1 expressing M2 phenotype during EAE. In addition, Th2 differentiation in beta actin-SRG3 Tg mice during EAE was associated with an increase in the basophil and mast cell populations and in IL4 production. Furthermore, the increased frequency of Treg cells in the spinal cord of beta-actin-SRG3 Tg mice might induce the suppression of and accelerate the recovery from EAE symptoms. Taken together, our results provide the first evidence supporting the development of a new therapeutic strategy for EAE involving the modulation of SRG3 expression to induce M2 and Th2 polarization, thereby inhibiting inflammatory immune responses. PMID- 26147221 TI - Treating Insomnia Disorder in the Context of Medical and Psychiatric Comorbidities. PMID- 26147222 TI - Establishment and effectiveness of inoculated arbuscular mycorrhizal fungi in agricultural soils. AB - Arbuscular mycorrhizal fungi (AMF) are promoted as biofertilizers for sustainable agriculture. So far, most researchers have investigated the effects of AMF on plant growth under highly controlled conditions with sterilized soil, soil substrates or soils with low available P or low inoculum potential. However, it is still poorly documented whether inoculated AMF can successfully establish in field soils with native AMF communities and enhance plant growth. We inoculated grassland microcosms planted with a grass-clover mixture (Lolium multiflorum and Trifolium pratense) with the arbuscular mycorrhizal fungus Rhizoglomus irregulare. The microcosms were filled with eight different unsterilized field soils that varied greatly in soil type and chemical characteristics and indigenous AMF communities. We tested whether inoculation with AMF enhanced plant biomass and R. irregulare abundance using a species specific qPCR. Inoculation increased the abundance of R. irregulare in all soils, irrespective of soil P availability, the initial abundance of R. irregulare or the abundance of native AM fungal communities. AMF inoculation had no effect on the grass but significantly enhanced clover yield in five out of eight field soils. The results demonstrate that AMF inoculation can be successful, even when soil P availability is high and native AMF communities are abundant. PMID- 26147223 TI - Effects of Warming on CO2 Fluxes in an Alpine Meadow Ecosystem on the Central Qinghai-Tibetan Plateau. AB - To analyze CO2 fluxes under conditions of climate change in an alpine meadow on the central Qinghai-Tibetan Plateau, we simulated the effect of warming using open top chambers (OTCs) from 2012 to 2014. The OTCs increased soil temperature by 1.62 degrees C (P < 0.05), but decreased soil moisture (1.38%, P < 0.05) during the experiments. The response of ecosystem CO2 fluxes to warming was variable, and dependent on the year. Under conditions of warming, mean gross ecosystem productivity (GEP) during the growing season increased significantly in 2012 and 2014 (P < 0.05); however, ecosystem respiration (ER) increased substantially only in 2012 (P < 0.05). The net ecosystem CO2 exchange (NEE) increased marginally in 2012 (P = 0.056), did not change in 2013(P > 0.05), and increased significantly in 2014 (P = 0.034) under conditions of warming. The GEP was more sensitive to climate variations than was the ER, resulting in a large increase in net carbon uptake under warming in the alpine meadow. Under warming, the 3-year averages of GEP, ER, and NEE increased by 19.6%, 15.1%, and 21.1%, respectively. The seasonal dynamic patterns of GEP and NEE, but not ER, were significantly impacted by warming. Aboveground biomass, particularly the graminoid biomass increased significantly under conditions of warming. Soil moisture, soil temperature, and aboveground biomass were the main factors that affected the variation of the ecosystem CO2 fluxes. The effect of warming on inter- and intra-annual patterns of ecosystem CO2 fluxes and the mechanism of different sensitivities in GEP and ER to warming, require further researched. PMID- 26147225 TI - National Trends in Hospital Readmission Rates among Medicare Fee-for-Service Survivors of Mitral Valve Surgery, 1999-2010. AB - BACKGROUND: Older patients who undergo mitral valve surgery (MVS) have high 1 year survival rates, but little is known about the experience of survivors. Our objective was to determine trends in 1-year hospital readmission rates and length of stay (LOS) in these individuals. METHODS: We included 100% of Medicare Fee-for Service patients >=65 years of age who underwent MVS between 1999-2010 and survived to 1 year (N = 146,877). We used proportional hazards regression to analyze the post-MVS 1-year readmission rate in each year, mean hospital LOS (after index admission), and readmission rates by subgroups (age, sex, race). RESULTS: The 1-year survival rate among patients undergoing MVS was 81.3%. Among survivors, 49.1% experienced a hospital readmission within 1 year. The post-MVS 1 year readmission rate declined from 1999-2010 (49.5% to 46.9%, P<0.01), and mean hospital LOS decreased from 6.2 to 5.3 (P<0.01). Readmission rates were highest in oldest patients, but declined in all age subgroups (65-74: 47.4% to 44.4%; 75 84: 51.4% to 49.2%, >=85: 56.4% to 50.0%, all P<0.01). There were declines in women and men (women: 51.7% to 50.8%, P<0.01; men: 46.9% to 43.0%, P<0.01), and in whites and patients of other race, but not in blacks (whites: 49.0% to 46.2%, P<0.01; other: 55.0% to 48.9%, P<0.01; blacks: 58.1% to 59.0%, P = 0.18). CONCLUSIONS: Among older adults surviving MVS to 1 year, slightly fewer than half experience a hospital readmission. There has been a modest decline in both the readmission rate and LOS over time, with worse outcomes in women and blacks. PMID- 26147226 TI - Assessment of respiration-induced vertebral motion in prone-positioned patients during general anaesthesia. AB - BACKGROUND: Robotic techniques are beginning to be applied to spine surgery, but safety is always a concern. Respiration-induced motion during surgery could lead to inaccurate robot-assisted pedicle screw placement. Accurate positional information for vertebral movement is needed to develop new techniques to eliminate or adjust respiration-induced motion and improve the accuracy of robotic spine surgery. METHODS: An optical tracking system was attached to patients' backs to track the motion of the C3, C7, T7, T12, L4 and S1 vertebral bodies. Monitoring was done in the operating room, with patients under general anaesthesia. RESULTS: Measured motion (peak to peak) during breathing was greater in T7 (2.2593 mm), T12 (2.2665 mm) and L4 (1.6054 mm) than in other segments. Anterior-posterior motion was greater than either left-right or superior-inferior motion. CONCLUSION: During general anaesthesia, significant motion occurs in vertebral bodies, caused by breathing, especially in the lower thoracic and lumbar segments. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26147227 TI - Immunohistochemical Studies of Cytoskeletal and Extracellular Matrix Components in Dogfish Scyliorhinus canicula L. Notochordal Cells. AB - Immunofluorescence and immunohistochemical techniques were used to define the distribution of cytoskeletal (cytokeratin 8, vimentin) and extracellular matrix components (collagen type I, collagen type II, hyaluronic acid, and aggrecan) and bone morphogenetic proteins 4 and 7 (BMP4 and BMP7) in the notochord of the lesser spotted dogfish Scyliorhinus canicula L. Immunolocalization of hyaluronic acid was observed in the notochord, vertebral centrum, and neural and hemal arches, while positive labeling to aggrecan was observed in the ossified centrum, notochord, and the perichondrium of the hyaline cartilage. Type I collagen was observed in the mineralized cartilage of the vertebral bodies, the notochord, the fibrocartilage of intervertebral disc, and the perichondrium. A positive labeling to type II collagen was observed in the inner part of the cartilaginous vertebral centrum and the notochord, as well as in the neural arch and muscle tissue, but there was no appreciable labeling of the hyaline cartilage. The presence of both BMP4 and BMP7 was seen in the mineralized vertebral centrum, notochordal cells, and neural arch. The notochordal cells expressed both cytokeratin 8 and vimentin, but predominantly vimentin. Hyaluronic acid, collagen type I, and collagen type II expression confirmed the presence of a mixture of notochordal and fibrocartilaginous tissue in the intervertebral disc, while BMPs confirmed the presence of an ossification in the cartilaginous skeleton of the spotted dogfish. PMID- 26147228 TI - IMQ-induced skin inflammation in mice is dependent on IL-1R1 and MyD88 signaling but independent of the NLRP3 inflammasome. AB - The pathogenesis of inflammatory skin diseases such as psoriasis involves the release of numerous proinflammatory cytokines, including members of the IL-1 family. Here we report overexpression of IL-1alpha, IL-1beta, and IL-1 receptor antagonist mRNA, associated to expression of IL-23p19, IL-17A, and IL-22 in skin cells, upon topical application of the TLR7 agonist imiquimod (IMQ) in C57BL/6J mice. IMQ-induced skin inflammation was partially reduced in mice deficient for both IL-1alpha/IL-1beta or for IL-1 receptor type 1 (IL-1R1), but not in IL 1alpha- or IL-1beta-deficient mice, demonstrating the redundant activity of IL 1alpha and IL-1beta for skin inflammation. NLRP3 or apoptosis-associated Speck like protein containing a Caspase recruitment domain-deficient mice had no significant reduction of skin inflammation in response to IMQ treatment, mainly due to the redundancy of IL-1alpha. However, IMQ-induced skin inflammation was abolished in the absence of MyD88, the adaptor protein shared by IL-1R and TLR signaling pathways. These results are consistent with the TLR7 dependence of IMQ induced skin inflammation. Thus, IL-1R1 contributes to the IMQ-induced skin inflammation, and disruption of MyD88 signaling completely abrogates this response. PMID- 26147230 TI - Chemoselective N-Heterocyclic Carbene-Catalyzed Cascade of Enals with Nitroalkenes. AB - An unprecedented N-heterocyclic carbene catalyzed chemoselective and enantioselective cascade reaction of enals with nitroalkenes has been developed. A wide range of enantioenriched dihydrocoumarins has been prepared, and the reaction goes through an enolate intermediate generated under a catalytic process. PMID- 26147229 TI - Asbestos textile production linked to malignant peritoneal and pleural mesothelioma in women: Analysis of 28 cases in Southeast China. AB - BACKGROUND: Chrysotile had been used in asbestos textile workshops in Southeast China but a clear relation to mesothelioma is lacking. METHODS: All patients diagnosed with mesothelioma from 2003 to 2010 at Yuyao People's Hospital were re evaluated by multiple expert pathologists with immunohistochemistry and asbestos exposure data were collected. RESULTS: Of 43 patients with a mesothelioma diagnosis, 19 peritoneal and nine pleural cases were finally diagnosed as mesothelioma. All were females, and the mean age of the patients with peritoneal or pleural mesothelioma was 52.4 and 58.2 years, respectively. All these cases had a history of domestic or occupational exposure to chrysotile. Two-thirds of the patients were from two adjoining towns with multiple small asbestos textile workshops. Contamination of tremolite was estimated to be less than 0.3%. CONCLUSIONS: This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma. PMID- 26147224 TI - Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms. AB - Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS) with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events. PMID- 26147231 TI - Covalent Protein Labeling by Enzymatic Phosphocholination. AB - We present a new protein labeling method based on the covalent enzymatic phosphocholination of a specific octapeptide amino acid sequence in intact proteins. The bacterial enzyme AnkX from Legionella pneumophila has been established to transfer functional phosphocholine moieties from synthetically produced CDP-choline derivatives to N-termini, C-termini, and internal loop regions in proteins of interest. Furthermore, the covalent modification can be hydrolytically removed by the action of the Legionella enzyme Lem3. Only a short peptide sequence (eight amino acids) is required for efficient protein labeling and a small linker group (PEG-phosphocholine) is introduced to attach the conjugated cargo. PMID- 26147232 TI - Development and Applications of Disulfonimides in Enantioselective Organocatalysis. PMID- 26147234 TI - Factors affecting the content of the ursolic and oleanolic acid in apple peel: influence of cultivars, sun exposure, storage conditions, bruising and Penicillium expansum infection. AB - BACKGROUND: For health promotion and as part of natural plant protection, it might be of interest to increase the content of oleanolic acid (OA) and ursolic acid (UA) by biofortification in breeding programs, although the extent of the influence of genetic and environmental factors needs to be clarified. The objective of this study was to determine the effect of cultivar, sun exposure, storage, bruising and fungal infection on the OA and UA content in apple peel. RESULTS: Three apple cultivars with different ripening times--'Discovery' (early), 'Aroma' (middle) and 'Gloster' (late)--were investigated. The content of OA and UA was mainly influenced by cultivar and side subjected to sun exposure, and to a minor extent by storage and seasonal year. 'Gloster' had the highest OA and UA content of the investigated cultivars. OA and UA content on the shaded side was higher than that on the sun-exposed side in all three cultivars. Inoculation with Penicillium expansum did not have any consistent effect on OA or UA, except in a few cases where the levels decreased. CONCLUSION: OA and UA content can be increased by choice of cultivar in the breeding process and to some extent by cultural practice. PMID- 26147233 TI - A neural mediator of human anxiety sensitivity. AB - Advances in the neuroscientific understanding of bodily autonomic awareness, or interoception, have led to the hypothesis that human trait anxiety sensitivity (AS)-the fear of bodily autonomic arousal-is primarily mediated by the anterior insular cortex. Despite broad appeal, few experimental studies have comprehensively addressed this hypothesis. We recruited 55 individuals exhibiting a range of AS and assessed them with functional magnetic resonance imaging (fMRI) during aversive fear conditioning. For each participant, three primary measures of interest were derived: a trait Anxiety Sensitivity Index score; an in-scanner rating of elevated bodily anxiety sensations during fear conditioning; and a corresponding estimate of whole-brain functional activation to the conditioned versus nonconditioned stimuli. Using a voxel-wise mediation analysis framework, we formally tested for 'neural mediators' of the predicted association between trait AS score and in-scanner anxiety sensations during fear conditioning. Contrary to the anterior insular hypothesis, no evidence of significant mediation was observed for this brain region, which was instead linked to perceived anxiety sensations independently from AS. Evidence for significant mediation was obtained for the dorsal anterior cingulate cortex-a finding that we argue is more consistent with the hypothesized role of human cingulofrontal cortex in conscious threat appraisal processes, including threat-overestimation. This study offers an important neurobiological validation of the AS construct and identifies a specific neural substrate that may underlie high AS clinical phenotypes, including but not limited to panic disorder. PMID- 26147235 TI - Energy exchange network of inter-residue interactions within a thermally fluctuating protein molecule: A computational study. AB - Protein function is regulated not only by the structure but also by physical dynamics and thermal fluctuations. We have developed the computer program, CURrent calculation for proteins (CURP), for the flow analysis of physical quantities within thermally fluctuating protein media. The CURP program was used to calculate the energy flow within the third PDZ domain of the neuronal protein PSD-95, and the results were used to illustrate the energy exchange network of inter-residue interactions based on atomistic molecular dynamics simulations. The removal of the alpha3 helix is known to decrease ligand affinity by 21-fold without changing the overall protein structure; nevertheless, we demonstrated that the helix constitutes an essential part of the network graph. PMID- 26147236 TI - Psychiatric comorbidity effects on compensatory cognitive training outcomes for veterans with traumatic brain injuries. AB - OBJECTIVE: To investigate the influence of posttraumatic stress disorder (PTSD) diagnosis, and PTSD and depression severity, on the postconcussive symptom trajectory over the course of a 1-year study period. RESEARCH DESIGN: Secondary analysis of a randomized controlled trial comparing veterans who received supported employment combined with compensatory cognitive training to those who received supported employment only. Assessments were conducted at baseline, 3- (postintervention), 6-, and 12-months. Participants were 50 Operation Enduring and Iraqi Freedom (OEF/OIF) veterans with a history of mild to moderate traumatic brain injury (TBI) who were unemployed, seeking work, and who had neuropsychological impairment. Of all participants, 74% met diagnostic criteria for PTSD. All participants received supported employment and half of the sample also received Cognitive Symptom Management and Rehabilitation Therapy (CogSMART), a 12-session, manualized compensatory cognitive training intervention. RESULTS: Veterans with PTSD and greater depression severity endorsed significantly more severe postconcussive symptomatology at all assessment time points. However, the rate of CogSMART-associated improvement in postconcussive symptoms did not differ as a result of psychiatric symptomatology. CONCLUSION: Study results suggest that for veterans with a history of mild to moderate TBI, presence of comorbid PTSD or depressive symptoms should not preclude participation in cognitive rehabilitation interventions. PMID- 26147237 TI - Soldiers returning from deployment: A qualitative study regarding exposure, coping, and reintegration. AB - PURPOSE/OBJECTIVE: The purpose of this study was to qualitatively explore exposure to deployment-related physical and/or emotional trauma and associated symptoms among Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) soldiers. Interviews also focused on in-theater- and reintegration-related experiences. RESEARCH METHOD/DESIGN: OEF/OIF soldiers (N = 103) participated in semistructured interviews, and a qualitative descriptive methodology was used to analyze the data. RESULTS: Themes were identified regarding (a) common experiences related to emotional and physical traumas and associated symptoms and strategies for coping and making meaning of experiences and (b) how combat and reintegration experiences affected soldiers' senses of self, relationships with others, and functioning. CONCLUSIONS/IMPLICATIONS: Themes identified support a rethinking of deployment-related mild traumatic brain injury and posttraumatic stress disorder as discrete conditions. Dimensional versus categorical models should be considered. The findings also highlight experiences and potentially meaningful constructs (e.g., moral injury, moral repair) that can be used to inform research and clinical efforts aimed at improving the lives of those who have served. PMID- 26147239 TI - Individual and dyadic planning predicting pelvic floor exercise among prostate cancer survivors. AB - [Correction Notice: An Erratum for this article was reported in Vol 60(3) of Rehabilitation Psychology (see record 2015-40319-001). Aleksandra Luszczynska's institutional affiliation was incorrectly set as Warsaw School of Social Sciences and Humanities. It should have been University of Social Sciences and Humanities. All versions of this article have been corrected.] OBJECTIVE: Radical prostatectomy, a standard treatment for localized prostate cancer, is often followed by a recommendation to initiate and maintain pelvic floor exercise (PFE), to control postsurgery urinary incontinence. Previous studies showed that planning facilitated the uptake and maintenance of a new behavior. Whereas individual planning addresses the setting of plans by 1 person, dyadic planning refers to creating plans together with a partner on when, where, and how the individual target person will perform a behavior. Individual and dyadic planning of PFE, their development over time, and their associations with PFE were investigated. RESEARCH METHOD: In a correlational study, 175 prostate-cancer patients provided data at 1, 3, 5, and 7 months following the onset of incontinence. Individual planning of PFE by patients and dyadic planning of PFE between patients and their partners, PFE, and incontinence were assessed by patients' self-reports. RESULTS: Two-level models with repeated assessments nested in individuals revealed stable levels of individual planning of PFE over time in patients with higher incontinence severity, whereas patients with receding incontinence showed decreases. Independent of incontinence severity, a curvilinear increase followed by a decrease of dyadic planning of PFE across time emerged. Sequential associations of both planning strategies with PFE were found. Whereas individual planning was steadily associated with PFE, associations between dyadic planning and PFE were nonsignificant in the beginning, but increased over time. CONCLUSIONS: Findings point to the importance of individual planning for the adoption and maintenance of PFE, with dyadic planning being relevant for PFE maintenance only. PMID- 26147238 TI - Depressive symptoms in adults with spina bifida. AB - OBJECTIVE: To examine the prevalence of depressive symptoms in adults with spina bifida and identify contributing factors for depressive symptomatology. METHOD: Retrospective Cohort Study. Data collection was conducted at a regional adult spina bifida clinic. A total of 190 charts from adult patients with spina bifida were included. The main outcome measures were the Beck Depression Inventory-II (BDI-II) and the mobility domain of the Craig Handicap Assessment Reporting Technique-Short Form (CHART-SF). RESULTS: Of the 190 participants, 49 (25.8%) had BDI-II scores (14+) indicative of depressive symptomatology. Sixty-nine (36.3%) were on antidepressants to treat depressive symptoms, and 31 (63.3%) of those with clinical symptoms of depression were on antidepressants. Participants with a history of depressive symptoms may be as high as 45.7% if both participants with BDI-II scores 14+ and those with antidepressant use specifically for the purposes of depression treatment are combined. In this population, lower CHART-SF mobility score, expressing "emotional concerns" as a reason for the visit on an intake sheet, and use of antidepressant medications were significantly associated with depressive symptoms. CONCLUSIONS: Depressive symptomatology appears to be common and undertreated in this cohort of adults with spina bifida, which may warrant screening for emotional concerns in routine clinic appointments. Significant depressive symptoms are associated with fewer hours out of bed and fewer days leaving the house. Additional research is needed to assess the impact of interventions directed toward mobility on depression and in the treatment of depression in this patient population. PMID- 26147241 TI - Editorial. PMID- 26147240 TI - Discovery of New H2S Releasing Phosphordithioates and 2,3-Dihydro-2-phenyl-2 sulfanylenebenzo[d][1,3,2]oxazaphospholes with Improved Antiproliferative Activity. AB - Hydrogen sulfide (H2S) is now recognized as a physiologically important gasotransmitter. Compounds which release H2S slowly are sought after for their potential in therapy. Herein the synthesis of a series of phosphordithioates based on 1 (GYY4137) are described. Their H2S release profiles are characterized using 2,6-dansyl azide (2), an H2S specific fluorescent probe. Most compounds have anticancer activity in several solid tumor cell lines and are less toxic in a normal human lung fibroblast, WI38. A preferred compound, 14, with 10-fold greater anticancer activity than 1, was shown to release H2S in MCF7 cells using a cell active probe, 21. Both permeability and intracellular pH (pHi) were found to be significantly improved for 14 compared to 1. Furthermore, 14 was also negative in the AMES test for genotoxicity. Cyclization of these initial structures gave a series of 2,3-dihydro-2-phenyl-2 sulfanylenebenzo[d][1,3,2]oxazaphospholes, of which the simplest member, compound 22 (FW1256), was significantly more potent in cells. The improved therapeutic window of 22 in WI38 cells was compared with three other cell types. Potency of 22 was superior to 1 in MCF7 tumor spheroids and the mechanism of cell death was shown to be via apoptosis with an increase in cleaved PARP and activated caspase 7. Evidence of H2S release in cells is also presented. This work provides a "toolbox" of slow-release H2S donors useful for studies of H2S in biology and as potential therapeutics in cancer, inflammation, and cardiovascular disease. PMID- 26147242 TI - Self-Assembly of a Tripod Aromatic Rod into Stacked Planar Networks. AB - Threefold symmetric rigid-core molecules with an internally grafted poly(ethylene oxide) (PEO) chain were synthesized, and their self-assembled structures were characterized using differential scanning calorimetry, TEM, and 1D and 2D X-ray scatterings in the solid state. The tripod compounds based on short PEO chains (n=8, 13, 17, 21), self-assemble into 2D channel-like network structures, whereas the compound with the longest PEO chain (n=34) forms a lamellar liquid crystalline phase. The interiors of the channel structures are filled with flexible PEO chains along the double-walled aromatic circumference. In these channel-like networks, three aromatic rods connected in the meta-position to each other are superimposed in parallel to other adjacent molecules to form the double walled aromatic frameworks stacked perpendicular to the resulting channels. These are novel examples of supramolecular channel-like structures developed using amphiphilic diblock molecules based on a threefold symmetric rigid scaffold. PMID- 26147244 TI - Feasibility of using the computed tomography dose indices to estimate radiation dose to partially and fully irradiated brains in pediatric neuroradiology examinations. AB - The purpose of this study was two-fold: (a) to measure the dose to the brain using clinical protocols at our institution, and (b) to develop a scanner independent dosimetry method to estimate brain dose. Radiation dose was measured with a pediatric anthropomorphic phantom and MOSFET detectors. Six current neuroradiology protocols were used: brain, sinuses, facial bones, orbits, temporal bones, and craniofacial areas. Two different CT vendor scanners (scanner A and B) were used. Partial volume correction factors (PVCFs) were determined for the brain to account for differences between point doses measured by the MOSFETs and average organ dose. The CTDIvol and DLP for each protocol were recorded. The dose to the brain (mGy) for scanners A and B was 10.7 and 10.0 for the brain protocol, 7.8 and 3.2 for the sinus, 10.2 and 8.6 for the facial bones, 7.4 and 4.7 for the orbits and 1.6 and 1.9 for the temporal bones, respectively. On scanner A, the craniofacial protocol included a standard and high dose option; the dose measured for these exams was 3.9 and 16.9 mGy, respectively. There was only one craniofacial protocol on scanner B; the brain dose measured on this exam was 4.8 mGy. A linear correlation was found between DLP and brain dose with the conversion factors: 0.049 (R(2) = 0.87), 0.046 (R(2) = 0.89) for scanner A and B, and 0.048 (R(2) = 0.89) for both scanners. The range of dose observed was between 1.8 and 16.9 mGy per scan. This suggests that brain dose estimates may be made from DLP. PMID- 26147243 TI - Mono- and Cocultures of Bronchial and Alveolar Epithelial Cells Respond Differently to Proinflammatory Stimuli and Their Modulation by Salbutamol and Budesonide. AB - The aim of this study was to investigate the changes in transport and effectiveness of salbutamol sulfate (SAL) and budesonide (BD) following stimulation with transforming growth factor-beta (TGF-beta) in mono- and coculture models of bronchial and alveolar epithelium. Primary bronchial and alveolar epithelial cells, grown at air interface on filters, either as monocultures or in coculture with airway smooth muscle cells or alveolar macrophages, respectively, were stimulated with TGF-beta. The biological response was modulated by depositing aerosolized SAL and BD on bronchial and alveolar models, respectively. Barrier integrity, permeability to fluorescein-Na, transport of the deposited drug, and the pharmacological response to SAL (cAMP and IL-8 levels) or BD (IL-6 and -8 levels) were measured. While stimulation with TGF-beta did not have any significant effect on the transepithelial electrical resistance and permeability to fluorescein-Na in mono- and coculture models, transport of SAL and BD were affected in cultures from some of the patients (6 out of 12 for bronchial and 2 out of 4 for alveolar cells). The bronchial coculture showed a better responsiveness to SAL in terms of cAMP release than the monoculture. In contrast, the difference between alveolar mono- and cocultures to TGF-beta mediated interleukin release and its modulation by BD was less pronounced. Our data point to intrinsic differences in the transport of, and responsiveness to, SAL and BD when epithelial cell cultures originate from different patients. Moreover, if the biological responses (e.g., IL-8, cAMP) involve communication between different cell types, coculture models are more relevant to measure such effects than monocultures. PMID- 26147245 TI - Investigating the Counteracting Effect of Trehalose on Urea-Induced Protein Denaturation Using Molecular Dynamics Simulation. AB - Molecular dynamics simulations are performed to investigate the counteracting effect of trehalose against urea-induced denaturation of S-peptide analogue. The calculations of Calpha root-mean-square deviation, radius of gyration, and solvent-accessible surface area reveal that the peptide loses its native structure in aqueous 8 M urea solution at 310 K and that this unfolding process is prevented in the presence of trehalose. Interestingly, the native structure of the peptide in ternary mixed urea/trehalose solution is similar to that in the pure water system. The estimation of helical percentage of peptide residues as well as peptide-peptide intramolecular hydrogen bond number for different systems also support the above findings. Decomposition of protein-urea total interaction energy into electrostatic and van der Waals contributions shows that the presence of trehalose molecules makes the latter contribution unfavorable without affecting the former. These observations are further supported by preferential interaction calculations. Furthermore, the hydrogen bond analyses show that with the addition of urea molecules to the peptide-water system, the formation of peptide-urea hydrogen bonds takes place at the expense of peptide-water hydrogen bonds. In ternary mixed osmolytes system, because of formation of a considerable amount of peptide-trehalose hydrogen bonds, some urea molecules are excluded from the peptide surface. This essentially reduces the interaction between peptide and urea molecules, and because of this, we notice a reduction in the number of peptide-urea hydrogen bonds. Interestingly, the total number of peptide-solution species hydrogen bonds in the pure water system is very similar to that for the mixed osmolytes system. From these observations we infer that in the ternary solution, peptide-solution species hydrogen bonds are shared by water, urea, and trehalose molecules. The presence of trehalose in the mixed osmolyte system causes a significant reduction in the translational dynamics of water molecules. We discuss these results to understand the molecular explanation of trehalose's counteracting ability on urea-induced protein denaturation. PMID- 26147246 TI - Interlaboratory study to evaluate the robustness of capillary electrophoresis mass spectrometry for peptide mapping. AB - A collaborative study on the robustness and portability of a capillary electrophoresis-mass spectrometry method for peptide mapping was performed by an international team, consisting of 13 independent laboratories from academia and industry. All participants used the same batch of samples, reagents and coated capillaries to run their assays, whereas they utilized the capillary electrophoresis-mass spectrometry equipment available in their laboratories. The equipment used varied in model, type and instrument manufacturer. Furthermore, different types of sheath-flow capillary electrophoresis-mass spectrometry interfaces were used. Migration time, peak height and peak area of ten representative target peptides of trypsin-digested bovine serum albumin were determined by every laboratory on two consecutive days. The data were critically evaluated to identify outliers and final values for means, repeatability (precision within a laboratory) and reproducibility (precision between laboratories) were established. For relative migration time the repeatability was between 0.05 and 0.18% RSD and the reproducibility between 0.14 and 1.3% RSD. For relative peak area repeatability and reproducibility values obtained were 3-12 and 9-29% RSD, respectively. These results demonstrate that capillary electrophoresis-mass spectrometry is robust enough to allow a method transfer across multiple laboratories and should promote a more widespread use of peptide mapping and other capillary electrophoresis-mass spectrometry applications in biopharmaceutical analysis and related fields. PMID- 26147247 TI - Associations of pain and depression with marital status in patients diagnosed with Parkinson's disease. AB - BACKGROUND: Depression and pain are significant clinical problems that are comorbid with Parkinson's disease (PD). However, the relationship of these variables with the marital status of patients with PD has not been explored in previous studies. Therefore, the goal of this study was to assess the possible relationship between depression prevalence, depression severity, and pain interference with the marital status of the sufferers of PD. METHODS: This study included 40 patients and 40 healthy control participants who were assessed for depression prevalence and severity using The Hospital Anxiety and Depression Scale (HADS). The same individuals were also assessed for pain interference using the Brief Pain Inventory (BPI). RESULTS: When compared to the control groups, the PD (Single) group was found to have the highest prevalence of depression, followed by the PD (Married) group whereas the Control (Single) group was found to have a higher prevalence than the Control (Married) group (P < 0.0001). A main effect was found on depression severity (P < 0.0001), but no significant differences were observed between the PD groups. Lastly, PD (Single) patients had significantly greater pain interference scores than the PD (Married) patients (P < 0.05) with no other significant case-control or control-control group differences. CONCLUSION: Patient-spouse relationship, which indicates physical and emotional support may have a mitigating effect on patient outcomes of depression prevalence and pain interference. PMID- 26147248 TI - A two-domain protein triggers heat shock pathway and necrosis pathway both in model plant and nematode. AB - The entomopathogen Bacillus thuringiensis is equipped with multiple virulent factors. The genome sequence of B. thuringiensis YBT1520 revealed the presence of a two-domain protein named Nel which is composed of a necrosis-inducing phytophthora protein 1-like domain found in phytopathogens and a ricin B-like lectin domain. The merging of two distantly related domains is relatively rare. Nel induced necrosis and pathogen-triggered immunity (PTI) on model plants. The Nel also exhibited inhibition activity to nematode. Microscopic observation showed that the toxicity of Nel to nematodes targets the intestine. Quantitative proteomics revealed that Nel stimulated the host defence. The Nel thus possesses dual roles, as both toxin and elicitor. Remarkably, the Nel protein triggered a similar response, induction of the heat shock pathway and the necrosis pathway, in both model plants and nematodes. The unusual ability of Nel to function across kingdom suggests a highly conserved mechanism in eukaryotes that predates the divergence of plants and animal. It is also speculated that the two-domain protein is the result of horizontal gene transfer (HGT) between phytopathogens and entomopathogens. Our results provide an example that HGT occurs between members of different species or even genera with lower frequency are particularly important for evolution of new bacterial pathogen lineages with new virulence. Bacillus thuringiensis occupies the same ecological niches, plant and soil, as phytopathogens, providing the opportunity for gene exchange. PMID- 26147249 TI - Balloon-cell variant of the Spitz nevus. PMID- 26147251 TI - Biomarkers: Non-destructive Method for Predicting Meat Tenderization. AB - Meat tenderness is the primary and most important quality attribute for the consumers worldwide. Tenderness is the process of breakdown of collagen tissue in meat to make it palatable. The earlier methods of tenderness evaluation like taste panels and shear force methods are destructive, time consuming and ill suited as they requires removing a piece of steak from the carcass for performing the test. Therefore, a non-destructive method for predicting the tenderness would be more desirable. The development of a meat quality grading and guarantee system through muscle profiling research can help to meet this demand. Biomarkers have the ability to identify if an exposure has occurred. Biomarkers of the meat quality are of prime importance for meat industry, which has ability to satisfy consumers' expectations. The biomarkers so far identified have been then sorted and grouped according to their common biological functions. All of them refer to a series of biological pathways including glycolytic and oxidative energy production, cell detoxification, protease inhibition and production of Heat Shock Proteins. On this basis, a detailed analysis of these metabolic pathways helps in identifying tenderization of meat having some domains of interest. It was, therefore, stressed forward that biomarkers can be used to determine meat tenderness. This review article summarizes the uses of several biomarkers for predicting the meat tenderness. PMID- 26147252 TI - Cryofibrinogenaemia in a patient with multiple myeloma and necrotizing vasculitis. PMID- 26147253 TI - Preventive Genomic Sequencing in the General Population: Do PGS Fly? PMID- 26147250 TI - MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. AB - The TOR (target of rapamycin) kinase limits longevity by poorly understood mechanisms. Rapamycin suppresses the mammalian TORC1 complex, which regulates translation, and extends lifespan in diverse species, including mice. We show that rapamycin selectively blunts the pro-inflammatory phenotype of senescent cells. Cellular senescence suppresses cancer by preventing cell proliferation. However, as senescent cells accumulate with age, the senescence-associated secretory phenotype (SASP) can disrupt tissues and contribute to age-related pathologies, including cancer. MTOR inhibition suppressed the secretion of inflammatory cytokines by senescent cells. Rapamycin reduced IL6 and other cytokine mRNA levels, but selectively suppressed translation of the membrane bound cytokine IL1A. Reduced IL1A diminished NF-kappaB transcriptional activity, which controls much of the SASP; exogenous IL1A restored IL6 secretion to rapamycin-treated cells. Importantly, rapamycin suppressed the ability of senescent fibroblasts to stimulate prostate tumour growth in mice. Thus, rapamycin might ameliorate age-related pathologies, including late-life cancer, by suppressing senescence-associated inflammation. PMID- 26147255 TI - Looking for Trouble and Finding It. PMID- 26147254 TI - Looking for Trouble: Preventive Genomic Sequencing in the General Population and the Role of Patient Choice. AB - Advances in genomics have led to calls for developing population-based preventive genomic sequencing (PGS) programs with the goal of identifying genetic health risks in adults without known risk factors. One critical issue for minimizing the harms and maximizing the benefits of PGS is determining the kind and degree of control individuals should have over the generation, use, and handling of their genomic information. In this article we examine whether PGS programs should offer individuals the opportunity to selectively opt out of the sequencing or analysis of specific genomic conditions (the menu approach) or whether PGS should be implemented using an all-or-nothing panel approach. We conclude that any responsible scale-up of PGS will require a menu approach that may seem impractical to some, but that draws its justification from a rich mix of normative, legal, and practical considerations. PMID- 26147256 TI - Scrutinizing the Right Not to Know. PMID- 26147257 TI - Honey, I Sequenced the Kids: Preventive Genomics and the Complexities of Adolescence. PMID- 26147258 TI - The Role of Whole Genome and Whole Exome Sequencing in Preventive Genomic Sequencing Programs. PMID- 26147259 TI - Patient Choice and Preventive Genomic Sequencing--More Trouble Upstream. PMID- 26147260 TI - Variants of Unknown Significance and Their Impact on Autonomy. PMID- 26147261 TI - Next Generation DNA Sequencing: Always Allow an Opt Out. PMID- 26147262 TI - Double Trouble: Preventive Genomic Sequencing and the Case of Minors. PMID- 26147263 TI - Preventive Genomic Sequencing and Care of the Individual Patient. PMID- 26147264 TI - Futility in Chronic Anorexia Nervosa: A Concept Whose Time Has Not Yet Come. AB - Comparatively little scholarly attention has been given to the question of futility in chronic psychiatric disorders, with the exception of a small body of work on so-called end-stage anorexia nervosa (AN). A review of this literature provides the background for a critical examination of whether the concept of futility has any clinically meaningful, ethically justifiable, and legally defensible application to AN. In this article, the arguments for and against futility judgments in AN are analyzed with special emphasis on determinations of capacity in this serious mental illness. Parallels between the futility disputes in medical and psychiatric disorders, where applicable, will be drawn to further illuminate whether or not the concept that continued psychiatric treatment for AN is ever truly futile. PMID- 26147265 TI - Anorexia Nervosa, "Futility," and Category Errors. PMID- 26147266 TI - The Futility of Arguing About Medical Futility in Anorexia Nervosa: The Question Is How Would You Handle Highly Specific Circumstances? PMID- 26147267 TI - "Futility" Is a Failed Concept in Medical Decision Making: Its Use Should Be Abandoned. PMID- 26147268 TI - Is Resistance (N)ever Futile? A Response to "Futility in Chronic Anorexia Nervosa: A Concept Whose Time Has Not Yet Come" by Cynthia Geppert. PMID- 26147269 TI - Compulsory Treatment in Chronic Anorexia Nervosa by All Means? Searching for a Middle Ground Between a Curative and a Palliative Approach. PMID- 26147270 TI - Ms X: A Promising New View of Anorexia Nervosa, Futility, and End-of-Life Decisions in a Very Recent English Case. PMID- 26147271 TI - A Misunderstanding Concerning Futility. PMID- 26147272 TI - Prescribing Beer for Hospitalized Patients With Alcohol Use Disorder. PMID- 26147273 TI - Balancing Beneficence and Autonomy. PMID- 26147274 TI - A Problem with the Evidence Base. PMID- 26147275 TI - Customary Care for a Common Comorbidity. PMID- 26147276 TI - The Many Meanings of Beer in Ethics Consultation. PMID- 26147277 TI - A Dark Place. PMID- 26147278 TI - Depression, Capacity, and a Request to Discontinue Life-Sustaining Treatment. PMID- 26147279 TI - Making Treatment Choices From "Dark Places": A Role for Ethics Consultation. PMID- 26147280 TI - Expectation and Suffering With LVAD Deactivation. PMID- 26147281 TI - Ethics Preparedness for Public Health Emergencies: Recommendations From the Presidential Bioethics Commission. PMID- 26147282 TI - Reverberations of Racism and Sexism Through the Subjective Sexualities of Undergraduate Women of Color. AB - Young women of color (among others) face both subtle and overt discrimination on a regular basis, but few studies have examined relations between discrimination and sexual outcomes using quantitative tools. We surveyed 154 self-identified undergraduate women of color to examine connections between race- and sex-based discrimination and subjective sexual well-being (i.e., condom use self-efficacy and sexual life satisfaction) and also tested whether sexual autonomy mediated these relations. When examined individually, each form of discrimination was related negatively to condom use self-efficacy and sexual life satisfaction, such that as women reported more discrimination, they reported poorer sexual well being. However, when examining both racism and sexism as joint predictors, only racism remained significant and there were no racism * sexism interaction effects. In a path model, sexual autonomy mediated the relation between racism and each measure of subjective sexual well-being; racism was negatively related to sexual autonomy, which in turn was positively related to both condom use self efficacy and sexual life satisfaction. These findings are consistent with the broader literature on the negative impact of discrimination on various aspects of mental and physical health. They also reinforce the position that redressing social inequality is a vital component of promoting individual health. PMID- 26147283 TI - Evaluation of the antioxidant effects of melatonin on the larynx mucosa of rats exposed to environmental tobacco smoke. AB - OBJECTIVES: This study's aim was to investigate the effect of melatonin in terms of mitigating the effects of smoking on the laryngeal mucosa of rats exposed to environmental tobacco smoke. DESIGN: Rats were divided into four groups: Melatonin + Smoking group exposed to smoke with melatonin; Smoking group exposed to smoke without melatonin; Saline group not exposed to smoke without melatonin; Melatonin group not exposed to smoke with melatonin. CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were evaluated in plasma and tissues. Tissues were also examined the changes of squamous hyperplasia, keratosis, parakeratosis and epithelial hyperplasia by light microscope and the ultrastructural changes by electron microscope. RESULTS: Tissue SOD, CAT and GSH-Px activities were significantly higher in Saline and Melatonin groups than Melatonin + Smoking and Smoking groups. Plasma CuZn-SOD and CAT activities were significantly higher in Saline and Melatonin groups than Smoking group. Plasma GSH-Px showed no significant difference. The rate of epithelial hyperplasia was significantly higher in Smoking group than the other groups. The rate of parakeratosis was significantly higher in Smoking group than the other groups. The epithelial cells in Melatonin + Smoking group displayed, normal cell structure similar to those in Saline group under electron microscope. CONCLUSIONS: The study shows that smoking induces substantial pathological changes in the laryngeal mucosa and melatonin may have some beneficial effects in partially reversing smoking-induced laryngeal injury by inducing the expression of antioxidants; biochemical and histological outcomes also support these findings due to preventing tissue damage in laryngeal mucosa exposed to smoke. PMID- 26147284 TI - First Steps in Estimating Population Prevalence of Combined Alcohol and Energy Drink Use. PMID- 26147285 TI - Kidney Transplantation Significantly Improves Patient and Graft Survival Irrespective of BMI: A Cohort Study. AB - Obesity and end-stage renal disease (ESRD) are on the increase worldwide. Kidney transplantation is the treatment of choice for ESRD. However, obesity is considered a contraindication for transplantation. We investigated the effect of BMI on mortality in transplanted and patients remaining on the waiting list in the United Kingdom. We analyzed the UK Renal Registry (RR) and the National Health Service Blood and Transplant (NHSBT) Organ Donation and Transplantation data for patients listed from January 1, 2004 to December 31, 2010, with follow up until December 31, 2011. Seventeen thousand six hundred eighty-one patients were listed during the study period, with BMI recorded for 13 526 (77%). One- and five-year patient survival was significantly better in all BMI bands (<18.5, 18.5 <25, 25-<30, 30-<35, 35-<40, and 40+kg/m(2) ) in the transplant group when compared to those who remained on the waiting list (p < 0.0001). The analyses were repeated excluding live donor transplants and the results were essentially the same. On analyses of patient survival with BMI as a continuous variable or using 5 kg weight bands, there was no cut-off observed in the higher BMI patients where there would be no benefit to transplantation. For transplanted patients (N = 8088), there was no difference in patient or graft survival between the defined BMI bands. Thus, irrespective of BMI, patient survival is improved if transplanted. PMID- 26147287 TI - Unsteady MHD Thin Film Flow of an Oldroyd-B Fluid over an Oscillating Inclined Belt. AB - This paper studies the unsteady magnetohydrodynamics (MHD) thin film flow of an incompressible Oldroyd-B fluid over an oscillating inclined belt making a certain angle with the horizontal. The problem is modeled in terms of non-linear partial differential equations with some physical initial and boundary conditions. This problem is solved for the exact analytic solutions using two efficient techniques namely the Optimal Homotopy Asymptotic Method (OHAM) and Homotopy Perturbation Method (HPM). Both of these solutions are presented graphically and compared. This comparison is also shown in tabular form. An excellent agreement is observed. The effects of various physical parameters on velocity have also been studied graphically. PMID- 26147286 TI - UV-Stressed Daphnia pulex Increase Fitness through Uptake of Vitamin D3. AB - Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3. PMID- 26147288 TI - Chemotherapy plus Erlotinib versus Chemotherapy Alone for Treating Advanced Non Small Cell Lung Cancer: A Meta-Analysis. AB - BACKGROUND: Whether a combination of chemotherapy and erlotinib is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of chemotherapy plus erlotinib versus chemotherapy alone for treating advanced NSCLC. METHODS: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015). RESULTS: Nine randomized controlled trials with a total of 3599 patients were included. Compared to chemotherapy alone, chemotherapy plus erlotinib was superior in PFS (HR = 0.76 [95% CI 0.62, 0.92], P = 0.006), and no statistically significant difference was observed in OS (HR = 0.94 [95% CI 0.86, 1.03], P = 0.16). Intercalated erlotinib plus chemotherapy demonstrated improvements in PFS (HR = 0.67 [95% CI 0.50, 0.91], P = 0.009) and OS (HR = 0.82 [95% CI 0.69, 0.98], P = 0.03). Continuous erlotinib plus chemotherapy treatment failed to demonstrate improvements in PFS (HR = 0.91 [95% CI 0.80, 1.04], P = 0.16) and OS (HR = 0.98 [95% CI 0.89, 1.09], P = 0.75). The association of chemotherapy plus erlotinib with improvement in PFS was significant in never smoking patients (HR = 0.46 [95% CI 0.37, 0.56], P<0.00001) but not in smoking patients (HR = 0.70 [95% CI 0.49, 1.00], P = 0.05). Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01). Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06). CONCLUSION: Combination of chemotherapy and erlotinib is a viable treatment option for patients with NSCLC, especially for patients who never smoked and patients with EGFR mutation-positive disease. In addition, intercalated administration is an effective combinatorial strategy. PMID- 26147289 TI - Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is an autoimmune disease which has a significant socio economic impact. The aim of the current study was to investigate eight candidate RA susceptibility loci to identify the associated variants in Egyptian population. Eight single nucleotide polymorphisms (SNPs) (MTHFR-C677T and A1298C, TGFbeta1 T869C, TNFB A252G, and VDR-ApaI, BsmI, FokI, and TaqI) were tested by genotyping patients with RA (n = 105) and unrelated controls (n = 80). Associations were tested using multiplicative, dominant, recessive, and co dominant models. Also, the linkage disequilibrium (LD) between the VDR SNPs was measured to detect any indirect association. By comparing RA patients with controls (TNFB, BsmI, and TaqI), SNPs were associated with RA using all models. MTHFR C677T was associated with RA using all models except the recessive model. TGFbeta1 and MTHFR A1298C were associated with RA using the dominant and the co dominant models. The recessive model represented the association for ApaI variant. There were no significant differences for FokI and the presence of RA disease by the used models examination. For LD results, There was a high D' value between BsmI and FokI (D' = 0.91), but the r(2) value between them was poor. All the studied SNPs may contribute to the susceptibility of RA disease in Egyptian population except for FokI SNP. PMID- 26147290 TI - A Statistical Method for the Analysis of Speech Intelligibility Tests. AB - Speech intelligibility tests are conducted on hearing-impaired people for the purpose of evaluating the performance of a hearing device under varying listening conditions and device settings or algorithms. The speech reception threshold (SRT) is typically defined as the signal-to-noise ratio (SNR) at which a subject scores 50% correct on a speech intelligibility test. An SRT is conventionally measured with an adaptive procedure, in which the SNR of successive sentences is adjusted based on the subject's scores on previous sentences. The SRT can be estimated as the mean of a subset of the SNR levels, or by fitting a psychometric function. A set of SRT results is typically analyzed with a repeated measures analysis of variance. We propose an alternative approach for analysis, a zero-and one inflated beta regression model, in which an observation is a single sentence score rather than an SRT. A parametrization of the model is defined that allows efficient maximum likelihood estimation of the parameters. Fitted values from this model, when plotted against SNR, are analogous to a mean psychometric function in the traditional approach. Confidence intervals for the fitted value curves are obtained by parametric bootstrap. The proposed approach was applied retrospectively to data from two studies that assessed the speech perception of cochlear implant recipients using different sound processing algorithms under different listening conditions. The proposed approach yielded mean SRTs for each condition that were consistent with the traditional approach, but were more informative. It provided the mean psychometric curve of each condition, revealing differences in slope, i.e. differential performance at different parts of the SNR spectrum. Another advantage of the new method of analysis is that results are stated in terms of differences in percent correct scores, which is more interpretable than results from the traditional analysis. PMID- 26147291 TI - Selective Impact of Disease on Coral Communities: Outbreak of White Syndrome Causes Significant Total Mortality of Acropora Plate Corals. AB - Coral diseases represent a significant and increasing threat to coral reefs. Among the most destructive diseases is White Syndrome (WS), which is increasing in distribution and prevalence throughout the Indo-Pacific. The aim of this study was to determine taxonomic and spatial patterns in mortality rates of corals following the 2008 outbreak of WS at Christmas Island in the eastern Indian Ocean. WS mainly affected Acropora plate corals and caused total mortality of 36% of colonies across all surveyed sites and depths. Total mortality varied between sites but was generally much greater in the shallows (0-96% of colonies at 5 m depth) compared to deeper waters (0-30% of colonies at 20 m depth). Site-specific mortality rates were a reflection of the proportion of corals affected by WS at each site during the initial outbreak and were predicted by the initial cover of live Acropora plate cover. The WS outbreak had a selective impact on the coral community. Following the outbreak, live Acropora plate coral cover at 5 m depth decreased significantly from 7.0 to 0.8%, while the cover of other coral taxa remained unchanged. Observations five years after the initial outbreak revealed that total Acropora plate cover remained low and confirmed that corals that lost all their tissue due to WS did not recover. These results demonstrate that WS represents a significant and selective form of coral mortality and highlights the serious threat WS poses to coral reefs in the Indo-Pacific. PMID- 26147293 TI - Competition and Facilitation between a Disease and a Predator in a Stunted Prey Population. AB - The role of diseases and parasites has received relatively little attention in modelling ecological dynamics despite mounting evidence of their importance in structuring communities. In contrast to predators, parasites do not necessarily kill their host but instead they may change host life history. Here, we study the impact of a parasite that selectively infects juvenile prey individuals and prevents them from maturing into adults. The model is inspired by the Ligula intestinalis tape worm and its cyprinid fish host Rutilis rutilis. We demonstrate that the parasite can promote as well as demote the so-called stunting in its host population, that is, the accumulation of juvenile prey, which leads to strong exploitation competition and consequently to a bottleneck in maturation. If competition between infected and uninfected individuals is strong, stunting will be enhanced and bistability between a stunted and non-stunted prey population occurs. In this case, the disease competes with the predator of its host species, possibly leading to predator extinction. In contrast, if the competition between infected and uninfected individuals is weak, the stunting is relieved, and epi-zoonotic cycles will occur, with recurrent epidemic outbreaks. Here, the disease facilitates the predator, and predator density will be substantially increased. We discuss the implications of our results for the dynamics and structure of the natural Ligula-Roach system. PMID- 26147292 TI - The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression. AB - Endothelial cells lining the walls of blood vessels are exposed simultaneously to wall shear stress (WSS) and circumferential stress (CS) that can be characterized by the temporal phase angle between WSS and CS (stress phase angle - SPA). Regions of the circulation with highly asynchronous hemodynamics (SPA close to 180 degrees ) such as coronary arteries are associated with the development of pathological conditions such as atherosclerosis and intimal hyperplasia whereas more synchronous regions (SPA closer to 0 degrees ) are spared of disease. The present study evaluates endothelial cell gene expression of 42 atherosclerosis related genes under asynchronous hemodynamics (SPA=-180 degrees ) and synchronous hemodynamics (SPA=0 degrees ). This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA=0 or SPA=-180. Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10+/-10 dyne/cm2) and CS (4 +/- 4%) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 degrees , most of them pro-atherogenic, including NFkappaB and other NFkappaB target genes. The up regulation of NFkappaB p50/p105 and p65 by SPA =-180 degrees was confirmed by Western blots and immunofluorescence staining demonstrating the nuclear translocation of NFkappaB p50/p105 and p65. These data suggest that asynchronous hemodynamics (SPA=-180 degrees ) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease. PMID- 26147294 TI - A Novel Insertion Variant of CRYGD Is Associated with Congenital Nuclear Cataract in a Chinese Family. AB - OBJECTIVE: To investigate a novel insertion variant of CRYGD identified in a Chinese family with nuclear congenital cataract. METHODS: A Chinese family with congenital nuclear cataract was recruited for the mutational screening of candidate genes by direct sequencing. Recombinant N-terminal Myc tagged wildtype or mutant CRYGD was expressed in HEK293T cells. The expression pattern, protein solubility and subcellular distribution were analyzed by western blotting and immunofluorescence. PRINCIPAL FINDINGS: A novel insertion variant, c.451_452insGACT, in CRYGD was identified in the patients. It causes a frameshift and a premature termination of the polypeptide to become Y151*. A significantly reduced solubility was observed for this mutant. Unlike wildtype CRYGD, which existed mainly in the cytoplasm, Y151* was mis-located in the nucleus. CONCLUSIONS: We have identified a novel mutation, c.451_452insGACT, in CRYGD, which is associated with nuclear cataract. This is the first insertion mutation of CRYGD found to cause autosomal dominant congenital cataract. The mutant protein, with loss of solubility and localization to the nucleus, is hypothesized to be the major cause of cataract in these patients. PMID- 26147295 TI - Frequency and time to onset of community-acquired respiratory tract infections in patients receiving esomeprazole: a retrospective analysis of patient-level data in placebo-controlled studies. AB - BACKGROUND: Debate continues on whether a causal association exists between the use of proton pump inhibitors (PPIs) and the risk of respiratory tract infections, in particular pneumonia. AIM: To investigate the occurrence of community-acquired respiratory tract infections, including pneumonia, in patients receiving esomeprazole. METHOD: A retrospective investigation of pooled data on adverse events related to respiratory tract infections, originally reported in 24 randomised, double-blind clinical studies, was conducted. The frequencies of respiratory tract infections and their relative risks were calculated retrospectively for the total patient population (9602 patients receiving esomeprazole and 5500 receiving placebo) and for sub-populations defined according to sex, age, esomeprazole dose, indication and geographical region. The cumulative frequency of first occurrence of events was calculated over 180 days. RESULTS: Frequencies of respiratory tract infections were similar in patients receiving esomeprazole and in those receiving placebo (any respiratory tract infection or signs/symptoms potentially indicating an respiratory tract infection, 0.278 and 0.296 patients per patient-year; lower respiratory tract infections, 0.048 and 0.058 per patient-year; pneumonia, 0.006 and 0.009 per patient-year, respectively). The relative risk for any respiratory tract infection in patients receiving esomeprazole compared with placebo was 0.94 (95% CI, 0.86-1.04). For lower respiratory tract infections, the relative risk was 0.82 (95% CI, 0.65-1.03) and for pneumonia, 0.66 (95% CI, 0.36-1.22). Sub analyses by demographics, dose and indication yielded similar results to the overall analysis. The occurrence of respiratory tract infections was evenly distributed over time and similar in the esomeprazole and placebo groups. CONCLUSION: There is no causal association between treatment with esomeprazole and the occurrence of community-acquired respiratory tract infections, including pneumonia. PMID- 26147296 TI - Adiponectin enhances Imatinib anti-tumour activity in human chronic myeloid leukaemia cells with serum levels associated with Imatinib efficacy in early chronic phase patients. AB - OBJECTIVES: Adiponectin, a functional ligand of adiponectin receptor-1 (AdipoR1) and adiponectin receptor-2 (AdipoR2), has been found to be linked to risk of development of chronic myeloid leukaemia (CML). Imatinib, as its first-line therapy, exhibits striking activity in both chronic and accelerated phases of the condition. However, numerous clinical trials have shown that many patients become refractory or experience relapses. Thus, development of new, hopefully effective Imatinib-based treatment strategies, are still needed. MATERIALS AND METHODS: Effects of recombinant adiponectin protein, in enhancing Imatinib anti-tumour activities, in K562 and MEG-01 CML cells, were examined in vitro and in vivo. Forty-eight consecutive newly diagnosed adult patients with Bcr-Abl-positive CML, in the early chronic phase (ECP), were enrolled in the study. Imatinib efficacy, plasma adiponectin levels and their correlations were analysed. RESULTS: Data presented here indicate that adiponectin enhanced Imatinib efficacy in vitro and in vivo. Furthermore, this augmented effect was due to inhibition of Bcr-Abl tyrosine kinase activity in an AdipoR1-dependent way, while AdipoR2 was not involved. Most importantly, additional clinical data revealed that adiponectin plasma levels in CML ECP patients, correlated with Imatinib efficacy. CONCLUSIONS: Adiponectin enhanced Imatinib anti-tumour activity in human chronic myeloid leukaemia cells and its serum levels were associated with Imatinib efficacy, in early chronic phase patients. PMID- 26147297 TI - Polarized Trafficking of AQP2 Revealed in Three Dimensional Epithelial Culture. AB - In renal collecting duct (CD) principal cells (PCs), vasopressin (VP) acts through its receptor, V2R, to increase intracellular cAMP leading to phosphorylation and apical membrane accumulation of the water channel aquaporin 2 (AQP2). The trafficking and function of basolaterally located AQP2 is, however, poorly understood. Here we report the successful application of a 3-dimensional Madin-Darby canine kidney (MDCK) epithelial model to study polarized AQP2 trafficking. This model recapitulates the luminal architecture of the CD and bi polarized distribution of AQP2 as seen in kidney. Without stimulation, AQP2 is located in the subapical and basolateral regions. Treatment with VP, forskolin (FK), or 8-(4-Chlorophenylthio)-2'-O-methyladenosine 3',5'-cyclic monophosphate monosodium hydrate (CPT-cAMP) leads to translocation of cytosolic AQP2 to the apical membrane, but not to the basolateral membrane. Treating cells with methyl beta-cyclodextrin (mbetaCD) to acutely block endocytosis causes accumulation of AQP2 on the basolateral membrane, but not on the apical membrane. Our data suggest that AQP2 may traffic differently at the apical and basolateral domains in this 3D epithelial model. In addition, application of a panel of phosphorylation specific AQP2 antibodies reveals the polarized, subcellular localization of differentially phosphorylated AQP2 at S256, S261, S264 and S269 in the 3D culture model, which is consistent with observations made in the CDs of VP treated animals, suggesting the preservation of phosphorylation dependent regulatory mechanism of AQP2 trafficking in this model. Therefore we have established a 3D culture model for the study of trafficking and regulation of both the apical and basolaterally targeted AQP2. The new model will enable further characterization of the complex mechanism regulating bi-polarized trafficking of AQP2 in vitro. PMID- 26147298 TI - A Cross-Sectional Study of the Cardiovascular Effects of Welding Fumes. AB - OBJECTIVES: Occupational exposure to particulate air pollution has been associated with an increased risk of cardiovascular disease. However, the risk to welders working today remains unclear. We aimed to elucidate the cardiovascular effects of exposure to welding fumes. METHODS: In a cross-sectional study, structured interviews and biological sampling were conducted for 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal breathing zone sampling of respirable dust was performed. Blood pressure (BP) and endothelial function (using peripheral arterial tonometry) were measured. Plasma and serum samples were collected from peripheral blood for measurement of C reactive protein, low-density lipoprotein, homocysteine, serum amyloid A, and cytokines. RESULTS: Welders were exposed to 10-fold higher levels of particles than controls. Welders had significantly higher BP compared to controls, an average of 5 mm Hg higher systolic and diastolic BP (P <= 0.001). IL-8 was 3.4 ng/L higher in welders (P=0.010). Years working as a welder were significantly associated with increased BP (beta=0.35, 95%CI 0.13 - 0.58, P=0.0024 for systolic BP; beta=0.32, 95%CI 0.16 - 0.48, P<0.001 for diastolic BP, adjusted for BMI) but exposure to respirable dust was not associated with BP. No clear associations occurred between welding and endothelial function, or other effect markers. CONCLUSIONS: A modest increase in BP was found among welders compared to controls suggesting that low-to-moderate exposure to welding fumes remains a risk factor for cardiovascular disease. PMID- 26147299 TI - Thermodynamics and H2 Transfer in a Methanogenic, Syntrophic Community. AB - Microorganisms in nature do not exist in isolation but rather interact with other species in their environment. Some microbes interact via syntrophic associations, in which the metabolic by-products of one species serve as nutrients for another. These associations sustain a variety of natural communities, including those involved in methanogenesis. In anaerobic syntrophic communities, energy is transferred from one species to another, either through direct contact and exchange of electrons, or through small molecule diffusion. Thermodynamics plays an important role in governing these interactions, as the oxidation reactions carried out by the first community member are only possible because degradation products are consumed by the second community member. This work presents the development and analysis of genome-scale network reconstructions of the bacterium Syntrophobacter fumaroxidans and the methanogenic archaeon Methanospirillum hungatei. The models were used to verify proposed mechanisms of ATP production within each species. We then identified additional constraints and the cellular objective function required to match experimental observations. The thermodynamic S. fumaroxidans model could not explain why S. fumaroxidans does not produce H2 in monoculture, indicating that current methods might not adequately estimate the thermodynamics, or that other cellular processes (e.g., regulation) play a role. We also developed a thermodynamic coculture model of the association between the organisms. The coculture model correctly predicted the exchange of both H2 and formate between the two species and suggested conditions under which H2 and formate produced by S. fumaroxidans would be fully consumed by M. hungatei. PMID- 26147300 TI - Changes in the sebaceous gland in patients with male pattern hair loss (androgenic alopecia). AB - BACKGROUND: The sebaceous gland and the follicular bulge region have important role in biology of the hair. They initiate destruction of the hair follicle both in human and animal models in certain conditions. The morphometric feature of the sebaceous gland is not well understood so as the distribution of the bulge stem cells in pathological conditions of male pattern hair loss or androgenic alopecia (AGA). OBJECTIVES: The authors perform morphometric analysis of the sebaceous gland in AGA patients and also study distribution of the follicular stem cells in the bulge region in these populations. METHODS: Two hundred and fifty cases of glass slide specimen from Japanese patients with male pattern hair loss were reviewed. Among these, 23 cases of the longitudinal (vertical) sections of the scalp skin with diagnosis of AGA were found and analyzed for the morphometric characteristics. Each sebaceous gland area was measured using NIH imagej system and statistically analyzed. For the identification of the follicular bulge region, an immunohistochemistry using anticytokeratin 15 (C8/144B clone) was carried out in the cases of AGA. RESULTS: The sebaceous gland area of the AGA group was noticeably increased, while the size of each sebaceous gland remains unchanged. It has more lobules in the hair follicular unit in the AGA population. In the immunohistochemistry, the follicular stem cells are present in the bulge regions in cases of AGA. CONCLUSIONS: The overgrowth (multilobulation) of the sebaceous gland and relative preservation of the follicular stem cells suggest that the changes in the sebaceous gland could be an important factor in the pathology of AGA. PMID- 26147301 TI - Correction: Integrated Copy Number and Expression Analysis Identifies Profiles of Whole-Arm Chromosomal Alterations and Subgroups with Favorable Outcome in Ovarian Clear Cell Carcinomas. PMID- 26147302 TI - Aging and Exercise Affect Hippocampal Neurogenesis via Different Mechanisms. AB - The rate of neurogenesis is determined by 1) the number of neural stem/progenitor cells (NSCs), 2) proliferation of NSCs, 3) neuron lineage specification, and 4) survival rate of the newborn neurons. Aging lowers the rate of hippocampal neurogenesis, while exercise (Ex) increases this rate. However, it remains unclear which of the determinants are affected by aging and Ex. We characterized the four determinants in different age groups (3, 6, 9, 12, 21 months) of mice that either received one month of Ex training or remained sedentary. Bromodeoxyuridine (BrdU) was injected two hours before sacrificing the mice to label the proliferating cells. The results showed that the number of newborn neurons massively decreased (>95%) by the time the mice reached nine months of age. The number of NSC was mildly reduced during aging, while Ex delayed such decline. The proliferation rates were greatly decreased by the time the mice were 9-month-old and Ex could not improve the rates. The rates of neuron specification were decreased during aging, while Ex increased the rates. The survival rate was not affected by age or Ex. Aging greatly reduced newborn neuron maturation, while Ex potently enhanced it. In conclusion, age-associated decline of hippocampal neurogenesis is mainly caused by reduction of NSC proliferation. Although Ex increases the NSC number and neuron specification rates, it doesn't restore the massive decline of NSC proliferation rate. Hence, the effect of Ex on the rate of hippocampal neurogenesis during aging is limited, but Ex does enhance the maturation of newborn neurons. PMID- 26147303 TI - Sputum Bacterial and Fungal Dynamics during Exacerbations of Severe COPD. AB - The changes in the microbial community structure during acute exacerbations of severe chronic obstructive pulmonary disease (COPD) in hospitalized patients remain largely uncharacterized. Therefore, further studies focused on the temporal dynamics and structure of sputum microbial communities during acute exacerbation of COPD (AECOPD) would still be necessary. In our study, the use of molecular microbiological techniques provided insight into both fungal and bacterial diversities in AECOPD patients during hospitalization. In particular, we examined the structure and varieties of lung microbial community in 6 patients with severe AECOPD by amplifying 16S rRNA V4 hyper-variable and internal transcribed spacer (ITS) DNA regions using barcoded primers and the Illumina sequencing platform. Sequence analysis showed 261 bacterial genera representing 20 distinct phyla, with an average number of genera per patient of >157, indicating high diversity. Acinetobacter, Prevotella, Neisseria, Rothia, Lactobacillus, Leptotrichia, Streptococcus, Veillonella, and Actinomyces were the most commonly identified genera, and the average total sequencing number per sputum sample was >10000 18S ITS sequences. The fungal population was typically dominated by Candia, Phialosimplex, Aspergillus, Penicillium, Cladosporium and Eutypella. Our findings highlight that COPD patients have personalized structures and varieties in sputum microbial community during hospitalization periods. PMID- 26147304 TI - 3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population. AB - MicroRNAs play an important role in cancer initiation and development. The aim of this study was to investigate whether polymorphisms in miRNA machinery genes are associated with the development of colorectal cancer (CRC). RAN rs14035 CT heterozygotes and T allele carriers (CT + TT) genotypes had lower risk of CRC, while the DICER1 rs3742330, DROSHA rs10719, and XPO5 rs11077 polymorphisms were not associated with CRC in the full study sample. Specifically, male RAN rs14035 CT heterozygotes and XPO5 rs11077 AA genotype (CT/AA) carriers experienced reduced CRC susceptibility (both colon and rectal). Subgroup analysis demonstrated that the combined RAN rs14035 CT + TT genotype was associated with rectal cancer, but not colon cancer. In addition, the DICER1 rs3742330 AG genotype was associated with a significantly increased risk of colon cancer. Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer. In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate. Furthermore, patients diagnosed with hypertension or DM who carried the DROSHA rs10719 CC genotype showed increased CRC risk, while the XPO5 rs11077 AC+CC genotype led to increased CRC risk in patients with hypertension only. Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC. PMID- 26147306 TI - Native and Prosthetic Valve Emergencies. AB - Native valvular emergencies are nearly always regurgitant in nature, whereas acute prosthetic valve dysfunction can be either regurgitant or stenotic. Regardless of the etiology, the presentation of acute valvular pathology differs significantly from chronic disease in both clinical presentation and in its appearance on diagnostic modalities, and appropriate recognition is critical to the choice of the appropriate therapeutic modality. Intrinsic to the recognition of a valvular emergency is a knowledge of those conditions for which a high index of suspicion must be maintained. This article addresses the etiologies, presentation, and diagnosis of these conditions and presents the relevant data that bears on which therapy may be most appropriate for which condition. PMID- 26147305 TI - Understanding the Interplay between Expression, Mutation and Activity of ALK Receptor in Rhabdomyosarcoma Cells for Clinical Application of Small-Molecule Inhibitors. AB - BACKGROUND: Receptor tyrosine kinases (RTKs) have a central role in cancer initiation and progression, since changes in their expression and activity potentially results in cell transformation. This concept is essential from a therapeutic standpoint, as clinical evidence indicates that tumours carrying deregulated RTKs are particularly susceptible to their activity but also to their inhibition. Rhabdomyosarcoma (RMS) is an aggressive childhood cancer where emerging therapies rely on the use kinase inhibitors, and among druggable kinases ALK represents a potential therapeutic target to commit efforts against. However, the functional relevance of ALK in RMS is not known, likewise the multi-component deregulated RTK profile to which ALK belongs. METHODS: In this study we used RMS cell lines representative of the alveolar and embrional histotype and looked at ALK intracellular localization, activity and cell signalling. RESULTS: We found that ALK was properly located at the plasma membrane of RMS cells, though in an unphosphorylated and inactive state due to intracellular tyrosine phosphatases (PTPases) activity. Indeed, increase of ALK phosphorylation was observed upon PTPase inhibition, as well as after ligand binding or protein overexpression. In these conditions, ALK signalling proceeded through the MAPK/ERK and PI3K/AKT pathways, and it was susceptible to ATP-competitive inhibitors exposure. However, drug-induced growth inhibition, cell cycle arrest and apoptosis did not correlate with ALK expression only, but relied also on the expression of other RTKs with akin drug binding affinity. Indeed, analysis of baseline and inducible RTK phosphorylation confirmed that RMS cells were susceptible to ALK kinase inhibitors even in the absence of the primary intended target, due to the presence of compensatory RTKs signalling pathways. CONCLUSIONS: These data, hence, provided evidences of a potentially active role of ALK in RMS cells, but also suggest caution in considering ALK a major therapeutic target in this malignancy, particularly if expression and activity cannot be accurately determined. PMID- 26147308 TI - Non-alcoholic fatty liver disease following liver transplantation: a clinical review. AB - Non-alcoholic steatohepatitis (NASH) is rapidly becoming the leading indication for liver transplantation (LT) in the United States. While post-transplantation outcomes are similar to other indications for transplant, recent evidence has suggested that reduction in risk factors for post-transplant metabolic syndrome may impose a significant survival benefit in this patient population. Cardiovascular mortality is the leading cause of death following transplantation for NASH. While pre-transplant pharmacologic and surgical approaches have been utilized to reduce cardiovascular risk factors following transplantation, the effectiveness of these treatment approaches in the post-transplant setting is poorly defined. Studies are urgently needed in the treatment of this rapidly growing population. PMID- 26147309 TI - Discrimination between Sedimentary Rocks from Close-Range Visible and Very-Near Infrared Images. AB - Variation in the mineral composition of rocks results in a change of their spectral response capable of being studied by imaging spectroscopy. This paper proposes the use of a low-cost handy sensor, a calibrated visible-very near infrared (VIS-VNIR) multispectral camera for the recognition of different geological formations. The spectral data was recorded by a Tetracam Mini-MCA-6 camera mounted on a field-based platform covering six bands in the spectral range of 0.530-0.801 um. Twelve sedimentary formations were selected in the Rhone-Alpes region (France) to analyse the discrimination potential of this camera for rock types and close-range mapping applications. After proper corrections and data processing, a supervised classification of the multispectral data was performed trying to distinguish four classes: limestones, marlstones, vegetation and shadows. After a maximum-likelihood classification, results confirmed that this camera can be efficiently exploited to map limestone-marlstone alternations in geological formations with this mineral composition. PMID- 26147310 TI - Communication in healthcare: a narrative review of the literature and practical recommendations. AB - OBJECTIVES: Effective and efficient communication is crucial in healthcare. Written communication remains the most prevalent form of communication between specialised and primary care. We aimed at reviewing the literature on the quality of written communication, the impact of communication inefficiencies and recommendations to improve written communication in healthcare. DESIGN: Narrative literature review. METHODS: A search was carried out on the databases PubMed, Web of Science and The Cochrane Library by means of the (MeSH)terms 'communication', 'primary health care', 'correspondence', 'patient safety', 'patient handoff' and 'continuity of patient care'. Reviewers screened 4609 records and 462 full texts were checked according following inclusion criteria: (1) publication between January 1985 and March 2014, (2) availability as full text in English, (3) categorisation as original research, reviews, meta-analyses or letters to the editor. RESULTS: A total of 69 articles were included in this review. It was found that poor communication can lead to various negative outcomes: discontinuity of care, compromise of patient safety, patient dissatisfaction and inefficient use of valuable resources, both in unnecessary investigations and physician worktime as well as economic consequences. CONCLUSION: There is room for improvement of both content and timeliness of written communication. The delineation of ownership of the communication process should be clear. Peer review, process indicators and follow-up tools are required to measure the impact of quality improvement initiatives. Communication between caregivers should feature more prominently in graduate and postgraduate training, to become engraved as an essential skill and quality characteristic of each caregiver. PMID- 26147311 TI - A Novel Lipase as Aquafeed Additive for Warm-Water Aquaculture. AB - A novel Acinetobacter lipase gene lipG1 was cloned from DNA extracted from intestinal sample of common carp (Cyprinus carpio), and expressed in E. coli BL21. The encoded protein was 406 amino acids in length. Phylogenetic analysis indicated that LipG1 and its relatives comprised a novel group of true lipases produced by Gram-negative bacteria. LipG1 showed maximal activity at 40C and pH 8.0 when pNP decanoate (C10) was used as the substrate, and remained high activity between 20C and 35C. Activity of the lipase was promoted by Ca2+ and Mg2+, and inhibited by Zn2+ and Cu2+. Moreover, LipG1 is stable with proteases, most commercial detergents and organic solvents. Substrate specificity test indicated that LipG1 can hydrolyse pNP esters with acyl chain length from C2 to C16, with preference for medium-chain pNP esters (C8, C10). Lastly, LipG1 was evaluated as an aquafeed additive for juvenile common carp (Cyprinus carpio). Results showed that supplementation of LipG1 significantly improved the gut and heptaopancreas lipase activity of fish fed with palm oil diet. Consistently, improved feed conversion ratio and growth performance were recorded in the LipG1 feeding group, to levels comparable to the group of fish fed with soybean oil diet. Collectively, LipG1 exhibited good potential as an aquafeed additive enzyme, and deserves further characterization as the representative of a novel group of lipases. PMID- 26147312 TI - Allocation, stress tolerance and carbon transport in plants: how does phloem physiology affect plant ecology? AB - Despite the crucial role of carbon transport in whole plant physiology and its impact on plant-environment interactions and ecosystem function, relatively little research has tried to examine how phloem physiology impacts plant ecology. In this review, we highlight several areas of active research where inquiry into phloem physiology has increased our understanding of whole plant function and ecological processes. We consider how xylem-phloem interactions impact plant drought tolerance and reproduction, how phloem transport influences carbon allocation in trees and carbon cycling in ecosystems and how phloem function mediates plant relations with insects, pests, microbes and symbiotes. We argue that in spite of challenges that exist in studying phloem physiology, it is critical that we consider the role of this dynamic vascular system when examining the relationship between plants and their biotic and abiotic environment. PMID- 26147313 TI - Pressure production in oral vestibule during gum chewing. AB - The aim of this study was to record oral vestibule pressure (OVP) by the lip and cheek contraction during gum chewing, to examine the characteristics of these pressures and coordination between the OVP and jaw movement. The subjects were eight healthy adult men (mean age of 29.3 +/- 3.3 years). An experimental plate that incorporated four pressure sensors on the midline of the upper jaw (Ch. 1), upper right canine (Ch. 2), upper right first molar (Ch. 3) and upper left first molar (Ch. 4) was used for measuring OVP. The right masseter electromyogram (EMG) was recorded simultaneously. Subjects chewed gum on the right side 20 times, and eight consecutive strokes were used for the analysis of the sequential order, maximal magnitude and duration of each OVP. Onset of OVP was observed at the molar on the non-chewing side (Ch. 4) before chewing side (Ch. 3), and offset was largely simultaneous at each site. On the chewing side (Chs. 1-3), OVP onset during the interval of EMG activity reached to the peak around the end of interval and offset in the duration of EMG activity. The maximal pressure was significantly larger at Chs. 1-3 than at Ch. 4, but no significant differences were observed in duration of pressure among each site. These results suggest that OVP is coordinated with jaw movement during gum chewing, and larger pressure is produced on the chewing side than on the non-chewing side. Our findings are quantitative indices for the evaluation of lip and cheek function during mastication. PMID- 26147314 TI - Neuropeptide Arginine Vasotocin Positively Affects Neurosteroidogenesis in the Early Brain of Grouper, Epinephelus coioides. AB - The neuropeptide arginine vasotocin (AVT) has versatile physiological functions in non-mammalian vertebrates. However, the functional association between AVT and neurosteroidogenesis in the early brain of teleosts remains elusive. We thus studied the developmental expression patterns of the avt gene and their V1 type receptor (avt-rv1 ) at various stages of development [90-150 days after hatching (dah)] in relation to neurosteroidogenesis and oestrogen signalling in the early brain of the orange-spotted grouper (Epinephelus coioides). avt and avt-rv1 mRNAs displayed a significantly increase in expression at 110 dah in the telencephalon and diencephalon. Further, avt mRNAs were localised in three magnocellular neuronal populations of the preoptic area, such as parvocellular, magnocellular and gigantocellular preoptic neurones. Intriguingly, the avt transcripts in those neurones were more abundant in 110 dah compared to other ages. Subsequently, dual fluorescence in situ hybridisation analysis showed that the avt and avt-rv1 genes were highly coexpressed with cyp11a1, hsd3b1, cyp17a1, eralpha, erbeta and gpr30, which indicates their potential for functional association. Cyp19a1b immunoreactive positive fibres were found in close proximity to avt-expressing neurones. Moreover, our results showed that exogenous Avt caused a significant increase in the cellular and gene levels of steroidogenic enzymes and oestrogen receptors (ers), whereas the administration of an Avt-rv1 antagonist caused a decrease in the expression of both steroidogenic enzymes and ers genes in the brain. Furthermore, exogenous oestradiol (E2 ) strongly up-regulated avt mRNAs in the grouper brain. Taken together, the present studies suggest that avt and steroidogenesis may positively work together to increase both E2 biosynthesis and early brain development. PMID- 26147315 TI - Efficacy of the Brain Injury Family Intervention: Impact on Family Members. AB - OBJECTIVE: Examine the effectiveness of an intervention (Brain Injury Family Intervention) for family caregivers after acquired brain injury. RESEARCH DESIGN: Prospective, controlled repeated-measures design. METHODS: The Brain Injury Family Intervention was designed as a whole family approach to addressing needs, emphasizing education, skill building, and psychological support. One hundred eight families of outpatients were assigned to either a treatment or wait list control group. The manualized treatment focused on highly relevant topics (eg, common injury effects, coping with loss and change, communication, and stress management) and was composed of five 2-hour sessions with outcome measurement pretreatment, posttreatment, and at 3 months following. Outcome measures included the Family Needs Questionnaire, the Service Obstacles Scale, and the Zarit Burden Interview. RESULTS: Treatment group caregivers showed an increase in met needs, greater satisfaction with services, and reduced burden relative to pretesting, whereas controls did not. Between-group differences for Professional Support needs were identified. CONCLUSIONS: Investigation provided evidence that a curriculum-based education, skill-building, and support intervention can benefit caregivers for up to 3 months. Additional research is needed to ascertain the longer-term benefits of intervention and the efficacy of alternative delivery methods (eg, via telephone and the Internet). PMID- 26147316 TI - Examining the Efficacy of the Modified Story Memory Technique (mSMT) in Persons With TBI Using Functional Magnetic Resonance Imaging (fMRI): The TBI-MEM Trial. AB - BACKGROUND: New learning and memory deficits are common following traumatic brain injury (TBI). Yet few studies have examined the efficacy of memory retraining in TBI through the most methodologically vigorous randomized clinical trial. Our previous research has demonstrated that the modified Story Memory Technique (mSMT) significantly improves new learning and memory in multiple sclerosis. METHODOLOGY: The present double-blind, placebo-controlled, randomized clinical trial examined changes in cerebral activation on functional magnetic resonance imaging following mSMT treatment in persons with TBI. Eighteen individuals with TBI were randomly assigned to treatment (n = 9) or placebo (n = 9) groups. RESULTS: Baseline and follow-up functional magnetic resonance imaging was collected during a list-learning task. Significant differences in cerebral activation from before to after treatment were noted in regions belonging to the default mode network and executive control network in the treatment group only. Results are interpreted in light of these networks. CONCLUSIONS: Activation differences between the groups likely reflect increased use of strategies taught during treatment. This study demonstrates a significant change in cerebral activation resulting from the mSMT in a TBI sample. Findings are consistent with previous work in multiple sclerosis. Behavioral interventions can show significant changes in the brain, validating clinical utility. PMID- 26147317 TI - Safety and Feasibility of a Very Early Verticalization in Patients With Severe Traumatic Brain Injury. PMID- 26147318 TI - N-Propargyl Caffeate Amide (PACA) Potentiates Nerve Growth Factor (NGF)-Induced Neurite Outgrowth and Attenuates 6-Hydroxydopamine (6-OHDA)-Induced Toxicity by Activating the Nrf2/HO-1 Pathway. AB - Insufficient production of neurotrophic factors is implicated in the pathogenesis of various neurodegenerative disorders. The aim of the present study was to evaluate the potential of N-propargyl caffeate amide (PACA) to enhance nerve growth factor (NGF)-induced neurite outgrowth and the underlying mechanisms. We discovered that PACA not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine (6-OHDA) neurotoxicity in dopaminergic PC12 cells and primary rat midbrain neurons. To identify the PACA-binding proteins, we introduced a biotin tag to the covalent PACA-protein adducts via "click chemistry" alkyne-azido cycloaddition. As a result, kelch-like ECH-associated protein 1 (Keap1) was isolated as the predominant protein from PACA treated PC12 cells. We demonstrated that the formation of PACA-Keap1 conjugates induced the nuclear translocation of transcription factor Nrf2 and the expression of antioxidant heme oxygenase-1 (HO-1). Importantly, specific HO-1 inhibitor SnPP diminished the neuroprotective and neuritogenic activities of PACA. Moreover, PACA attenuated 6-OHDA-induced production of neurotoxic reactive oxygen species and reactive nitrogen species. PACA also preserved mitochondrial membrane integrity and enhanced the cellular resistance against 6-OHDA neurotoxicity. These results suggest that PACA may exhibit neuroprotective and neuritogenic activities via activating the Nrf2/HO-1 antioxidant pathway. PMID- 26147319 TI - Refractory highly disfiguring lupus pernio: a dramatic and prolonged response to infliximab. PMID- 26147320 TI - Endocan: a new biomarker associated with inflammation in type 2 diabetes mellitus? PMID- 26147321 TI - Local area disadvantage and gambling involvement and disorder: Evidence for gene environment correlation and interaction. AB - Previous research has demonstrated that local area characteristics (such as disadvantage and gambling outlet density) and genetic risk factors are associated with gambling involvement and disordered gambling. These 2 lines of research were brought together in the present study by examining the extent to which genetic contributions to individual differences in gambling involvement and disorder contributed to being exposed to, and were also accentuated by, local area disadvantage. Participants were members of the national community-based Australian Twin Registry who completed a telephone interview in which the past year frequency of gambling and symptoms of disordered gambling were assessed. Indicators of local area disadvantage were based on census data matched to the participants' postal codes. Univariate biometric model-fitting revealed that exposure to area disadvantage was partially explained by genetic factors. Bivariate biometric model-fitting was conducted to examine the evidence for gene environment interaction while accounting for gene-environment correlation. These analyses demonstrated that: (a) a small portion of the genetic propensity to gamble was explained by moving to or remaining in a disadvantaged area, and (b) the remaining genetic and unique environmental variation in the frequency of participating in electronic machine gambling (among men and women) and symptoms of disordered gambling (among women) was greater in more disadvantaged localities. As the gambling industry continues to grow, it will be important to take into account the multiple contexts in which problematic gambling behavior can emerge-from genes to geography-as well as the ways in which such contexts may interact with each other. PMID- 26147322 TI - Pupillary reactivity to sad stimuli as a biomarker of depression risk: Evidence from a prospective study of children. AB - The primary aim of the current study was to examine whether physiological reactivity to depression-relevant stimuli, measured via pupil dilation, serves as a biomarker of depression risk among children of depressed mothers. Participants included 47 mother-child dyads. All mothers had a history of major depressive disorder. Pupil dilation was recorded while children viewed angry, happy, and sad faces. Follow-up assessments occurred 6, 12, 18, and 24 months after the initial assessment, during which structured interviews were used to assess for children's levels of depressive symptoms as well as the onset of depressive diagnoses. Children exhibiting relatively greater pupil dilation to sad faces experienced elevated trajectories of depressive symptoms across the follow-up as well as a shorter time to depression onset. These findings were not observed for children's pupillary reactivity to angry or happy faces. The current findings suggest that physiological reactivity to sad stimuli, assessed using pupillometry, serves as a potential biomarker of depression risk among children of depressed mothers. Notably, pupillometry is an inexpensive tool that could be administered in clinical settings, such as pediatricians' offices, to help identify which children of depressed mothers are at highest risk for developing depression themselves. PMID- 26147323 TI - (Dis)connected: An examination of interoception in individuals with suicidality. AB - Sensing one's internal physiological sensations is a process known as interoception. Several lines of research suggest that poor interoception may facilitate engagement in dangerous self-harm. In 2 studies, we investigated interoceptive abilities in individuals with differing degrees of suicidality. In Study 1, we compared interoception in controls (n = 27) and suicide ideators (n = 35), planners (n = 14), and attempters (n = 30). We found that those with suicidality had worse interoception than controls. Further, attempters reported worse interoception than planners or ideators. In Study 2, we compared interoception in psychiatric outpatients who had (n = 136) or had not (n = 459) attempted suicide. Again, we found that attempters reported worse interoception than nonattempters. In addition, we found that recent attempts were more strongly associated with interoceptive deficits than distant attempts. Together, our findings suggest that interoception is impaired in individuals with suicidality. Furthermore, the extent to which interoception is disturbed may differentiate not only between those who desire suicide from those who attempt suicide, but also between recent and distant suicide attempters. Impaired interoception may be important for engaging in serious self-injury; thus, reestablishing one's connection to the body may aid in the prevention of suicidal behavior. PMID- 26147325 TI - Factors affecting high school teacher adoption, sustainability, and fidelity to the "Youth@Work: Talking Safety" curriculum. AB - BACKGROUND: Our objective was to identify individual- and organizational-level factors that affect high school teacher adoption, sustainability, and fidelity to the occupational safety and health curriculum, "Youth@Work: Talking Safety." METHODS: We analyzed survey data collected from 104 high school teachers across the US who were trained in the curriculum since 2004. Linear and Cox regression were used to examine bivariate associations between individual and organizational level factors and the outcomes of interest. RESULTS: Except for perceived complexity, all individual-level factors (acceptance, enthusiasm, teaching methods fit, and self-efficacy) were associated with one or more outcomes of interest (P-values ranged from <0.001 to 0.031). Priority for non-academic courses (P = 0.035) and supportive organizational climate (P = 0.037) were the organizational-level factors associated with sustainability and number of lessons delivered, respectively. CONCLUSIONS: Consistent with the literature, individual level factors influenced teacher adoption and, to a lesser extent, sustainability, and fidelity to the Youth@Work: Talking Safety curriculum and should be considered in attempts to promote the curriculum's use in high schools. PMID- 26147324 TI - Undifferentiated negative affect and impulsivity in borderline personality and depressive disorders: A momentary perspective. AB - Individuals with borderline personality disorder (BPD) often report experiencing several negative emotions simultaneously, an indicator of "undifferentiated" negative affect. The current study examined the relationship between undifferentiated negative affect and impulsivity. Participants with a current BPD (n = 67) or depressive disorder (DD; n = 38) diagnosis carried an electronic diary for 28 days, reporting on emotions and impulsivity when randomly prompted (up to 6 times per day). Undifferentiated negative affect was quantified using momentary intraclass correlation coefficients, which indicated how consistently negative emotion items were rated across fear, hostility, and sadness subscales. Undifferentiated negative affect at the occasion-level, day-level, and across 28 days was used to predict occasion-level impulsivity. Multilevel modeling was used to test the hypothesis that undifferentiated negative emotion would be a significant predictor of momentary impulsivity above and beyond levels of overall negative affect. Undifferentiated negative affect at the occasion and day levels were significant predictors of occasion-level impulsivity, but undifferentiated negative affect across the 28-day study period was only marginally significant. Results did not differ depending on BPD or DD status, though individuals with BPD did report significantly greater momentary impulsivity and undifferentiated negative affect. Undifferentiated negative affect may increase risk for impulsivity among individuals with BPD and depressive disorders, and the current data suggest that this process can be relatively immediate as well as cumulative over the course of a day. This research supports the consideration of undifferentiated negative affect as a transdiagnostic construct, but one that may be particularly relevant for those with BPD. PMID- 26147327 TI - How Does Substitutional Doping Affect Visible Light Absorption in a Series of Homodisperse Ti11 Polyoxotitanate Nanoparticles? AB - Homodisperse doped polyoxotitanate nanoclusters with formulae Ti11 (MX)O14 (OiPr)17 (M=Mn, Fe or Co; X=Cl, Br or I, OiPr=isopropoxide) display strongly dopant-dependent properties. Spectroscopic solution and reflectance measurements backed up by density of states and time-dependent DFT calculations based on the determined structures, show the prominent effect of FeX substitution by decreasing the HOMO-LUMO gap of the particles. The effect is attributed to the presence of an occupied Fe beta orbital halfway up the bandgap, leading to long wavelength absorption with electron transfer to the titanium atoms of the cluster. Whereas the light absorption varies significantly with variation of the transition metal dopant, its dependency on the nature of the halogen atom or the change in dipole moment across the series is minor. PMID- 26147328 TI - Atomic layer deposition in nanostructured photovoltaics: tuning optical, electronic and surface properties. AB - Nanostructured materials offer key advantages for third-generation photovoltaics, such as the ability to achieve high optical absorption together with enhanced charge carrier collection using low cost components. However, the extensive interfacial areas in nanostructured photovoltaic devices can cause high recombination rates and a high density of surface electronic states. In this feature article, we provide a brief review of some nanostructured photovoltaic technologies including dye-sensitized, quantum dot sensitized and colloidal quantum dot solar cells. We then introduce the technique of atomic layer deposition (ALD), which is a vapor phase deposition method using a sequence of self-limiting surface reaction steps to grow thin, uniform and conformal films. We discuss how ALD has established itself as a promising tool for addressing different aspects of nanostructured photovoltaics. Examples include the use of ALD to synthesize absorber materials for both quantum dot and plasmonic solar cells, to grow barrier layers for dye and quantum dot sensitized solar cells, and to infiltrate coatings into colloidal quantum dot solar cell to improve charge carrier mobilities as well as stability. We also provide an example of monolayer surface modification in which adsorbed ligand molecules on quantum dots are used to tune the band structure of colloidal quantum dot solar cells for improved charge collection. Finally, we comment on the present challenges and future outlook of the use of ALD for nanostructured photovoltaics. PMID- 26147329 TI - Effect of Screening Mammography on Cancer Incidence and Mortality. PMID- 26147326 TI - Fish, n - 3 polyunsaturated fatty acids and n - 6 polyunsaturated fatty acids intake and breast cancer risk: The Japan Public Health Center-based prospective study. AB - Limited and inconsistent studies exist on the association between the intake of fish, n - 3 polyunsaturated fatty acids (PUFA) and n - 6 PUFA and breast cancer. Fish and n - 3 PUFA support various body functions and are thought to reduce the carcinogenesis risk while n - 6 PUFA may have a positive association with cancer risk. We examined the association between intake of fish, n - 3 PUFA [including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA)] and n - 6 PUFA and breast cancer with subanalyses on estrogen (ER) and progesterone receptor (PR) status. We investigated 38,234 Japanese women aged 45-74 years from the Japan Public Health Center-based prospective study (JPHC study), and during 14.1 years of follow-up time, 556 breast cancer cases were newly diagnosed. Breast cancer risk was not associated with the intake of total fish, n - 3 PUFA and n - 6 PUFA when analyzed in totality through multivariable Cox proportional hazards regression models with age as the time scale. Intake of total n - 6 was positively associated with the development of ER+PR+ tumors [multivariable-adjusted HR Q4 vs. Q1 = 2.94 (95% CI: 1.26-6.89; ptrend = 0.02)]. Intake of EPA was associated with a decreased breast cancer risk for ER+PR+ tumors [multivariable-adjusted HR Q2 vs. Q1 = 0.47 (95% CI: 0.25-0.89; ptrend =0.47)]. While the overall association between the intake of total fish, n - 3 PUFA and n - 6 PUFA and breast cancer risk is null, for ER+PR+ tumors, a positive association was seen between n - 6 intake and breast cancer, and a marginally significant inverse association was observed for EPA intake. PMID- 26147330 TI - Perceived safety and benefit of community water fluoridation: 2009 HealthStyles survey. AB - OBJECTIVES: To describe perceived benefits and safety of community water fluoridation (CWF) and investigate factors associated with those perceptions of CWF among respondents to a proprietary survey in the United States. METHODS: We obtained data from the 2009 HealthStyles survey, a convenience sample of 4,556 respondents. Pearson's chi-squared and logistic regression were used to determine the associations between certain socio-demographic factors and perceptions regarding the safety and health benefits of CWF. RESULTS: The majority of respondents (55.3 percent) strongly agreed/agreed that CWF was safe, while 31.5 percent were neutral, and 13.2 percent disagreed/strongly disagreed. Twenty-seven percent of respondents reported CWF had no health benefit, 57.3 percent reported some benefit, and 15.5 percent reported great benefit. Perceived CWF safety and benefit in the bivariate analyses were associated with gender, age, race/ethnicity, education, marital status, income, sealant knowledge, CWF knowledge, past year dental utilization, and perceived vaccine safety. Respondents with knowledge of CWF (47.9 percent) were more likely to agree that it was safe (69.8 percent) than those who reported no knowledge (41.3 percent). Among respondents who said childhood vaccines were not safe (4.0 percent), almost half disagreed that CWF was safe. Logistic regression results indicated that perceived CWF safety and benefits increased with CWF knowledge, perceived vaccine safety, and income. CONCLUSIONS: Although only a minority of the US population perceived CWF as unsafe or providing no benefit to health, perceptions regarding CWF varied by knowledge of CWF and socio-demographic factors. Oral health promotion activities should consider these differing perceptions of CWF among groups to tailor oral health messaging appropriately. PMID- 26147331 TI - alpha,beta-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5'-Nucleotidase (CD73) Inhibitors. AB - ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor alpha,beta-methylene-ADP (AOPCP, adenosine-5'-O [(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N(6)-Monosubstitution was superior to symmetrical N(6),N(6) disubstitution. The most potent inhibitors were N(6)-(4-chlorobenzyl)- (10l, PSB 12441, Ki 7.23 nM), N(6)-phenylethyl- (10h, PSB-12425, Ki 8.04 nM), and N(6) benzyl-adenosine-5'-O-[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, Ki 9.03 nM). Replacement of the 6-NH group in 10g by O (10q, PSB-12431) or S (10r, PSB 12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 nM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nucleotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date. PMID- 26147332 TI - A bi-stable Pt(II) based molecular turnstile. AB - Playing with the competition between H- and coordination-bonds, a bi-stable unsymmetrical organometallic turnstile was designed and its dynamic behaviour was studied in solution using NMR techniques. The turnstile, bearing two differentiated interaction sites, is based on a stator, composed of a square planar Pt(II) centre equipped with one pyridyl group and one phenol moiety, connected to a symmetrical rotor bearing a pyridyl unit as either a H-bond acceptor or as a monodentate coordinating site. Whereas in the absence of a metallic effector, the turnstile is locked by a H-bond formed between the phenol moiety located on the stator and the pyridyl group of the rotor, in the presence of Ag(+) cations, the turnstile switches to another closed state resulting from the simultaneous binding of the cations by pyridyl units belonging to both the stator and the rotor. The switching process was shown to be reversible. PMID- 26147334 TI - Scientific Programme, 45th Annual Meeting of the International Continence Society (ICS), 6-9 October 2015, Montreal, Canada. PMID- 26147333 TI - Synthesis of Side-Chain Modified Polypeptides. PMID- 26147335 TI - Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions. AB - Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning. PMID- 26147336 TI - Current integration of dissection in medical education in Australia and New Zealand: Challenges and successes. AB - The reduced use of dissection associated with the introduction of integrated systems problem-based learning curricula, graduate-entry programs and medical school expansion is a frequent topic of discussion and debate in modern medical training. The purpose of this study was to investigate the impact of these changes to the medical education landscape, by looking at the current utilization and integration of dissection in medical schools, in Australia and New Zealand. A survey and an invitation to participate in an interview were distributed to all Australian Medical Council-accredited medical schools. Sixteen schools (76%) responded to the survey and five interviews (24%) were conducted. Dissection was a component of the medical program in 12 of the 16 schools surveyed. The opportunity for medical students to dissect human cadavers was found to be related to whether the medical school was established pre- or post-2000 (P = 0.003) but was not significantly associated to undergraduate- or graduate-entry (P = 0.64), program length (P = 0.59) or the number of commencing students (P = 0.07). The methods used for the delivery and integration of dissection varied between schools. Despite substantial changes to the delivery of anatomy in Australian and New Zealand medical schools, a variety of approaches have been adopted to ensure dissection remains an integral component of medical student education. Based on our findings, a number of recommendations were formulated to encourage the integration of dissection, regardless of the didactics of the program, to enhance the anatomical knowledge of students. PMID- 26147337 TI - Roles of DPY30 in the Proliferation and Motility of Gastric Cancer Cells. AB - Various types of histone methylation have been associated with cancer progression. Depending on the methylation site in histone proteins, its effects on transcription are different. DPY30 is a common member of SET1/MLL histone H3K4 methyltransferase complexes. However, its expression and roles in gastric cancer have been poorly characterized. To determine whether DPY30 has pathophysiological roles in gastric cancer, its expression and roles were examined. Immunohistochemistry and real time PCR showed up-regulation of DPY30 expression in some gastric cancer cell lines and patients' tissues. Its knockdown by siRNA decreased the proliferation, migration, and invasion of gastric cancer cells, whereas its overexpression showed the opposite effects. These results indicate that DPY30 has critical roles in the proliferation, migration, and invasion of gastric cancer cells, and suggest DPY30 might be a therapeutic target in gastric cancer. PMID- 26147338 TI - New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles. AB - Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower cytotoxic activity against Caco-2 cells. In conclusion this study offers a closer and critical point of view on preparation, in vitro and analytical evaluation of DMAB-stabilized PLGA nanoparticles for the physiological use. PMID- 26147339 TI - Microinverter Thermal Performance in the Real-World: Measurements and Modeling. AB - Real-world performance, durability and reliability of microinverters are critical concerns for microinverter-equipped photovoltaic systems. We conducted a data driven study of the thermal performance of 24 new microinverters (Enphase M215) connected to 8 different brands of PV modules on dual-axis trackers at the Solar Durability and Lifetime Extension (SDLE) SunFarm at Case Western Reserve University, based on minute by minute power and thermal data from the microinverters and PV modules along with insolation and environmental data from July through October 2013. The analysis shows the strengths of the associations of microinverter temperature with ambient temperature, PV module temperature, irradiance and AC power of the PV systems. The importance of the covariates are rank ordered. A multiple regression model was developed and tested based on stable solar noon-time data, which gives both an overall function that predicts the temperature of microinverters under typical local conditions, and coefficients adjustments reecting refined prediction of the microinverter temperature connected to the 8 brands of PV modules in the study. The model allows for prediction of internal temperature for the Enphase M215 given similar climatic condition and can be expanded to predict microinverter temperature in fixed-rack and roof-top PV systems. This study is foundational in that similar models built on later stage data in the life of a device could reveal potential influencing factors in performance degradation. PMID- 26147340 TI - Genetic influences on resting-state functional networks: A twin study. AB - Alterations in resting-state networks (RSNs) are often associated with psychiatric and neurologic disorders. Given this critical linkage, it has been hypothesized that RSNs can potentially be used as endophenotypes for brain diseases. To validate this notion, a critical step is to show that RSNs exhibit heritability. However, the investigation of the genetic basis of RSNs has only been attempted in the default-mode network at the region-of-interest level, while the genetic control on other RSNs has not been determined yet. Here, we examined the genetic and environmental influences on eight well-characterized RSNs using a twin design. Resting-state functional magnetic resonance imaging data in 56 pairs of twins were collected. The genetic and environmental effects on each RSN were estimated by fitting the functional connectivity covariance of each voxel in the RSN to the classic ACE twin model. The data showed that although environmental effects accounted for the majority of variance in wide-spread areas, there were specific brain sites that showed significant genetic control for individual RSNs. These results suggest that part of the human brain functional connectome is shaped by genomic constraints. Importantly, this information can be useful for bridging genetic analysis and network-level assessment of brain disorders. PMID- 26147341 TI - Reference Values and Age Differences in Body Composition of Community-Dwelling Older Japanese Men and Women: A Pooled Analysis of Four Cohort Studies. AB - OBJECTIVES: To determine age- and sex-specific body composition reference values and investigate age differences in these parameters for community-dwelling older Japanese men and women, using direct segmental multi-frequency bioelectrical impedance analysis. METHODS: We conducted a pooled analysis of data collected in four cohort studies between 2008 and 2012: Kusatsu Longitudinal Study, Hatoyama Cohort Study, Itabashi Cohort Study, and Kashiwa Cohort Study. The pooled analysis included cross-sectional data from 4478 nondisabled, community-dwelling adults aged 65-94 years (2145 men, 2333 women; mean age: 72.9 years in men and 72.6 years in women). Body weight, fat mass (FM), percentage FM, fat-free mass (FFM), and appendicular lean soft tissue mass were measured using the InBody 720 and 430 (Biospace Co. Ltd, Seoul, Korea). The values were then normalized by height in meters squared to determine body mass index (BMI), FM index (FMI), FFM index (FFMI), and skeletal muscle mass index (SMI). RESULTS: Simple means (standard deviation) of BMI, percentage FM, FMI, FFMI, and SMI were 23.4 (2.9) kg/m(2), 24.9 (6.3)%, 5.96 (2.09) kg/m(2), 17.4 (1.5) kg/m(2), and 7.29 (0.76) kg/m(2), respectively, in men and 22.7 (3.3) kg/m(2), 31.7 (7.1)%, 7.40 (2.61) kg/m(2), 15.3 (1.2) kg/m(2), and 5.86 (0.67) kg/m(2), respectively, in women. We then calculated quartiles and quintiles for these indices after stratifying for sex and 5-year age group. FFMI and SMI decreased significantly with age in both sexes (P < 0.001 for trends), but FFMI remained constant among the women with only a 1% decrease up to age 84 years. Percentage FM increased significantly, with age (P < 0.001 in men and P = 0.045 in women for trends), but FMI was unchanged in both sexes (P = 0.147 in men and P = 0.176 in women for trends). CONCLUSION: The present data should be useful in the clinical evaluation of body composition of older Japanese and for international comparisons. The small age related decrease in FFMI may be a noteworthy characteristic of body composition change in older Japanese women. PMID- 26147342 TI - Stronger Neural Modulation by Visual Motion Intensity in Autism Spectrum Disorders. AB - Theories of autism spectrum disorders (ASD) have focused on altered perceptual integration of sensory features as a possible core deficit. Yet, there is little understanding of the neuronal processing of elementary sensory features in ASD. For typically developed individuals, we previously established a direct link between frequency-specific neural activity and the intensity of a specific sensory feature: Gamma-band activity in the visual cortex increased approximately linearly with the strength of visual motion. Using magnetoencephalography (MEG), we investigated whether in individuals with ASD neural activity reflect the coherence, and thus intensity, of visual motion in a similar fashion. Thirteen adult participants with ASD and 14 control participants performed a motion direction discrimination task with increasing levels of motion coherence. A polynomial regression analysis revealed that gamma-band power increased significantly stronger with motion coherence in ASD compared to controls, suggesting excessive visual activation with increasing stimulus intensity originating from motion-responsive visual areas V3, V6 and hMT/V5. Enhanced neural responses with increasing stimulus intensity suggest an enhanced response gain in ASD. Response gain is controlled by excitatory-inhibitory interactions, which also drive high-frequency oscillations in the gamma-band. Thus, our data suggest that a disturbed excitatory-inhibitory balance underlies enhanced neural responses to coherent motion in ASD. PMID- 26147344 TI - Differential Effect of Oxicam Non-Steroidal Anti-Inflammatory Drugs on Membranes and Their Consequence on Membrane Fusion. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesics and antipyretics, which form an interesting drug group because of their new and alternate functions. The ability of the NSAIDs belonging to the oxicam chemical group to induce membrane fusion at low physiologically relevant concentrations is a new function that has drawn considerable attention. Membrane fusion is dependent on the interplay of physicochemical properties of both drugs and membranes. Here, we have elucidated the effects of different oxicam drugs, Meloxicam, Piroxicam, Tenoxicam, Lornoxicam, and Isoxicam, on an identical membrane-mimetic system. This highlights only the differential effects of the drugs on drug-membrane interactions, which in turn modulate their role as membrane fusogens. The partitioning behavior and the location of the drugs in dimyristoylphosphatidylcholine vesicles have been studied using second-derivative absorption spectroscopy, fluorescence quenching, steady-state fluorescence anisotropy, and time-resolved fluorescence lifetime measurements. Fusion kinetics has been monitored by fluorescence assays and dynamic light scattering was used to provide a snapshot of the vesicle diameter distribution at different time points. The differential perturbing effect of the drugs on the membrane is dependent both on their partitioning and location. Although partitioning governs the extent of fusion, the location modulates the rates of each step. PMID- 26147343 TI - PARADISE 24: A Measure to Assess the Impact of Brain Disorders on People's Lives. AB - OBJECTIVE: To construct a metric of the impact of brain disorders on people's lives, based on the psychosocial difficulties (PSDs) that are experienced in common across brain disorders. STUDY DESIGN: Psychometric study using data from a cross-sectional study with a convenience sample of 722 persons with 9 different brain disorders interviewed in four European countries: Italy, Poland, Spain and Finland. Questions addressing 64 PSDs were first reduced based on statistical considerations, patient's perspective and clinical expertise. Rasch analyses for polytomous data were also applied. SETTING: In and outpatient settings. RESULTS: A valid and reliable metric with 24 items was created. The infit of all questions ranged between 0.7 and 1.3. There were no disordered thresholds. The targeting between item thresholds and persons' abilities was good and the person-separation index was 0.92. Persons' abilities were linearly transformed into a more intuitive scale ranging from zero (no PSDs) to 100 (extreme PSDs). CONCLUSION: The metric, called PARADISE 24, is based on the hypothesis of horizontal epidemiology, which affirms that people with brain disorders commonly experience PSDs. This metric is a useful tool to carry out cardinal comparisons over time of the magnitude of the psychosocial impact of brain disorders and between persons and groups in clinical practice and research. PMID- 26147345 TI - Prevention of post-traumatic reinnervation with microtubule inhibitors. AB - OBJECTIVES/HYPOTHESIS: Functional recovery after a recurrent laryngeal nerve or facial nerve injury may be impaired due to aberrant reinnervation. Previous work in a rat peripheral nerve injury model found vincristine to be a potent inhibitor of reinnervation, and it has since been used to effectively block neural regeneration in other animal models. However, vincristine's narrow therapeutic index may limit its utility; therefore, another microtubule inhibitor, paclitaxel, which has a higher therapeutic index, was tested. STUDY DESIGN: Animal (rat) study. METHODS: After controlled injury to the rat posterior tibial (PT) nerve, the gastrocnemius/soleus complex was injected with saline (control, n = 14), vincristine (n = 30), or paclitaxel (n = 20). Injections without a crush injury were performed using saline (n = 5) or paclitaxel (n = 9). The functional recovery (FR) of the PT nerve was assessed using walking track analysis. RESULTS: At 6 weeks, controls had already recovered to baseline (FR = 1.0), whereas the paclitaxel group had FR = 0.724 +/- 0.064 and the vincristine group had FR = 0.709 +/- 0.078. At 6 months, the paclitaxel rats had FR = 0.798 +/- 0.167 and the vincristine rats had FR = 0.754 +/- 0.240. These differences were significantly different from baseline, but the two agents were not different from each other. Paclitaxel did not affect the FR in the absence of a nerve injury. CONCLUSIONS: Intramuscular paclitaxel and vincristine both significantly inhibit regeneration of the PT nerve after crush injury for at least 6 months. Potential clinical uses of inhibition of reinnervation are discussed. LEVEL OF EVIDENCE: NA PMID- 26147346 TI - Functional interactions among filamentous Epsilonproteobacteria and Bacteroidetes in a deep-sea hydrothermal vent biofilm. AB - Little is known about how lithoautotrophic primary production is connected to microbial organotrophic consumption in hydrothermal systems. Using a multifaceted approach, we analysed the structure and metabolic capabilities within a biofilm growing on the surface of a black smoker chimney in the Loki's Castle vent field. Imaging revealed the presence of rod-shaped Bacteroidetes growing as ectobionts on long, sheathed microbial filaments (> 100 MUm) affiliated with the Sulfurovum genus within Epsilonproteobacteria. The filaments were composed of a thick (> 200 nm) stable polysaccharide, representing a substantial fraction of organic carbon produced by primary production. An integrated -omics approach enabled us to assess the metabolic potential and in situ metabolism of individual taxonomic and morphological groups identified by imaging. Specifically, we provide evidence that organotrophic Bacteroidetes attach to and glide along the surface of Sulfurovum filaments utilizing organic polymers produced by the lithoautotrophic Sulfurovum. Furthermore, in situ expression of acetyl-CoA synthetase by Sulfurovum suggested the ability to assimilate acetate, indicating recycling of organic matter in the biofilm. This study expands our understanding of the lifestyles of Epsilonproteobacteria in hydrothermal vents, their metabolic properties and co-operative interactions in deep-sea hydrothermal vent food webs. PMID- 26147347 TI - Anagliptin, a potent dipeptidyl peptidase IV inhibitor: its single-crystal structure and enzyme interactions. AB - The single-crystal structure of anagliptin, N-[2-({2-[(2S)-2-cyanopyrrolidin-1 yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6 carboxamide, was determined. Two independent molecules were held together by intermolecular hydrogen bonds, and the absolute configuration of the 2 cyanopyrrolidine ring delivered from l-prolinamide was confirmed to be S. The interactions of anagliptin with DPP-4 were clarified by the co-crystal structure solved at 2.85 A resolution. Based on the structure determined by X-ray crystallography, the potency and selectivity of anagliptin were discussed, and an SAR study using anagliptin derivatives was performed. PMID- 26147348 TI - Biological and computational evaluation of resveratrol inhibitors against Alzheimer's disease. AB - It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates beta secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some "hits" led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action. PMID- 26147349 TI - Antioxidant activity of taxifolin: an activity-structure relationship. AB - Taxifolin is a kind of flavanonol, whose biological ability. The objectives of this study were to investigate the antioxidants and antiradical activities of taxifolin by using different in vitro bioanalytical antioxidant methods including DMPD?(+), ABTS?(+), [Formula: see text], and DPPH?-scavenging effects, the total antioxidant influence, reducing capabilities, and Fe(2+)-chelating activities. Taxifolin demonstrated 81.02% inhibition of linoleic acid emulsion peroxidation at 30 ug/mL concentration. At the same concentration, standard antioxidants including trolox, alpha-tocopherol, BHT, and BHA exhibited inhibitions of linoleic acid emulsion as 88.57, 73.88, 94.29, and 90.12%, respectively. Also, taxifolin exhibited effective DMPD?(+), ABTS?(+), [Formula: see text], and DPPH? scavenging effects, reducing capabilities, and Fe(2+)-chelating effects. The results obtained from this study clearly showed that taxifolin had marked antioxidant, reducing ability, radical scavenging and metal-chelating activities. Also, this study exhibits a scientific shore for the significant antioxidant activity of taxifolin and its structure-activity insight. PMID- 26147351 TI - Pattern Formation in Populations with Density-Dependent Movement and Two Interaction Scales. AB - We study the spatial patterns formed by a system of interacting particles where the mobility of any individual is determined by the population crowding at two different spatial scales. In this way we model the behavior of some biological organisms (like mussels) that tend to cluster at short ranges as a defensive strategy, and strongly disperse if there is a high population pressure at large ranges for optimizing foraging. We perform stochastic simulations of a particle level model of the system, and derive and analyze a continuous density description (a nonlinear diffusion equation). In both cases we show that this interplay of scale-dependent-behaviors gives rise to a rich formation of spatial patterns ranging from labyrinths to periodic cluster arrangements. In most cases these clusters have the very peculiar appearance of ring-like structures, i.e., organisms arranging in the perimeter of the clusters, which we discuss in detail. PMID- 26147350 TI - The Protein Level of Rev1, a TLS Polymerase in Fission Yeast, Is Strictly Regulated during the Cell Cycle and after DNA Damage. AB - Translesion DNA synthesis provides an alternative DNA replication mechanism when template DNA is damaged. In fission yeast, Eso1 (poleta), Kpa1/DinB (polkappa), Rev1, and Polzeta (a complex of Rev3 and Rev7) have been identified as translesion synthesis polymerases. The enzymatic characteristics and protein protein interactions of these polymerases have been intensively characterized; however, how these proteins are regulated during the cell cycle remains unclear. Therefore, we examined the cell cycle oscillation of translesion polymerases. Interestingly, the protein levels of Rev1 peaked during G1 phase and then decreased dramatically at the entry of S phase; this regulation was dependent on the proteasome. Temperature-sensitive proteasome mutants, such as mts2-U31 and mts3-U32, stabilized Rev1 protein when the temperature was shifted to the restrictive condition. In addition, deletion of pop1 or pop2, subunits of SCF ubiquitin ligase complexes, upregulated Rev1 protein levels. Besides these effects during the cell cycle, we also observed upregulation of Rev1 protein upon DNA damage. This upregulation was abolished when rad3, a checkpoint protein, was deleted or when the Rev1 promoter was replaced with a constitutive promoter. From these results, we hypothesize that translesion DNA synthesis is strictly controlled through Rev1 protein levels in order to avoid unwanted mutagenesis. PMID- 26147352 TI - Epigenetic Diversity of Clonal White Poplar (Populus alba L.) Populations: Could Methylation Support the Success of Vegetative Reproduction Strategy? AB - The widespread poplar populations of Sardinia are vegetatively propagated and live in different natural environments forming large monoclonal stands. The main goals of the present study were: i) to investigate/measure the epigenetic diversity of the poplar populations by determining their DNA methylation status; ii) to assess if and how methylation status influences population clustering; iii) to shed light on the changes that occur in the epigenome of ramets of the same poplar clone. To these purposes, 83 white poplar trees were sampled at different locations on the island of Sardinia. Methylation sensitive amplified polymorphism analysis was carried out on the genomic DNA extracted from leaves at the same juvenile stage. The study showed that the genetic biodiversity of poplars is quite limited but it is counterbalanced by epigenetic inter-population molecular variability. The comparison between MspI and HpaII DNA fragmentation profiles revealed that environmental conditions strongly influence hemi methylation of the inner cytosine. The variable epigenetic status of Sardinian white poplars revealed a decreased number of population clusters. Landscape genetics analyses clearly demonstrated that ramets of the same clone were differentially methylated in relation to their geographic position. Therefore, our data support the notion that studies on plant biodiversity should no longer be restricted to genetic aspects, especially in the case of vegetatively propagated plant species. PMID- 26147353 TI - Comment on: 'A Poisson resampling method for simulating reduced counts in nuclear medicine images'. AB - In order to be able to calculate half-count images from already acquired data, White and Lawson published their method based on Poisson resampling. They verified their method experimentally by measurements with a Co-57 flood source. In this comment their results are reproduced and confirmed by a direct numerical simulation in Matlab. Not only Poisson resampling, but also two direct redrawing methods were investigated. Redrawing methods were based on a Poisson and a Gaussian distribution. Mean, standard deviation, skewness and excess kurtosis half-count/full-count ratios were determined for all methods, and compared to the theoretical values for a Poisson distribution. Statistical parameters showed the same behavior as in the original note and showed the superiority of the Poisson resampling method. Rounding off before saving of the half count image had a severe impact on counting statistics for counts below 100. Only Poisson resampling was not affected by this, while Gaussian redrawing was less affected by it than Poisson redrawing. Poisson resampling is the method of choice, when simulating half-count (or less) images from full-count images. It simulates correctly the statistical properties, also in the case of rounding off of the images. PMID- 26147355 TI - DNA replication: Unlocking the secrets of fork arrest. PMID- 26147354 TI - Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy. AB - The gateway to morphine biosynthesis in opium poppy (Papaver somniferum) is the stereochemical inversion of (S)-reticuline since the enzyme yielding the first committed intermediate salutaridine is specific for (R)-reticuline. A fusion between a cytochrome P450 (CYP) and an aldo-keto reductase (AKR) catalyzes the S to-R epimerization of reticuline via 1,2-dehydroreticuline. The reticuline epimerase (REPI) fusion was detected in opium poppy and in Papaver bracteatum, which accumulates thebaine. In contrast, orthologs encoding independent CYP and AKR enzymes catalyzing the respective synthesis and reduction of 1,2 dehydroreticuline were isolated from Papaver rhoeas, which does not accumulate morphinan alkaloids. An ancestral relationship between these enzymes is supported by a conservation of introns in the gene fusions and independent orthologs. Suppression of REPI transcripts using virus-induced gene silencing in opium poppy reduced levels of (R)-reticuline and morphinan alkaloids and increased the overall abundance of (S)-reticuline and its O-methylated derivatives. Discovery of REPI completes the isolation of genes responsible for known steps of morphine biosynthesis. PMID- 26147357 TI - Enhanced-fluidity liquid chromatography using mixed-mode hydrophilic interaction liquid chromatography/strong cation-exchange retention mechanisms. AB - The potential of enhanced-fluidity liquid chromatography, a subcritical chromatography technique, in mixed-mode hydrophilic interaction/strong cation exchange separations is explored, using amino acids as analytes. The enhanced fluidity liquid mobile phases were prepared by adding liquefied CO2 to methanol/water mixtures, which increases the diffusivity and decreases the viscosity of the mixture. The addition of CO2 to methanol/water mixtures resulted in increased retention of the more polar amino acids. The "optimized" chromatographic performance (achieving baseline resolution of all amino acids in the shortest amount of time) of these methanol/water/CO2 mixtures was compared to traditional acetonitrile/water and methanol/water liquid chromatography mobile phases. Methanol/water/CO2 mixtures offered higher efficiencies and resolution of the ten amino acids relative to the methanol/water mobile phase, and decreased the required isocratic separation time by a factor of two relative to the acetonitrile/water mobile phase. Large differences in selectivity were also observed between the enhanced-fluidity and traditional liquid mobile phases. A retention mechanism study was completed, that revealed the enhanced-fluidity mobile phase separation was governed by a mixed-mode retention mechanism of hydrophilic interaction/strong cation-exchange. On the other hand, separations with acetonitrile/water and methanol/water mobile phases were strongly governed by only one retention mechanism, either hydrophilic interaction or strong cation exchange, respectively. PMID- 26147356 TI - Strand separation establishes a sustained lock at the Tus-Ter replication fork barrier. AB - The bidirectional replication of a circular chromosome by many bacteria necessitates proper termination to avoid the head-on collision of the opposing replisomes. In Escherichia coli, replisome progression beyond the termination site is prevented by Tus proteins bound to asymmetric Ter sites. Structural evidence indicates that strand separation on the blocking (nonpermissive) side of Tus-Ter triggers roadblock formation, but biochemical evidence also suggests roles for protein-protein interactions. Here DNA unzipping experiments demonstrate that nonpermissively oriented Tus-Ter forms a tight lock in the absence of replicative proteins, whereas permissively oriented Tus-Ter allows nearly unhindered strand separation. Quantifying the lock strength reveals the existence of several intermediate lock states that are impacted by mutations in the lock domain but not by mutations in the DNA-binding domain. Lock formation is highly specific and exceeds reported in vivo efficiencies. We postulate that protein-protein interactions may actually hinder, rather than promote, proper lock formation. PMID- 26147358 TI - Use of Cymbopogon citratus essential oil in food preservation: Recent advances and future perspectives. AB - The economic burdens and health implications of food spoilage are increasing. Contamination of food sources by fungi, bacteria, yeast, nematodes, insects, and rodents remains a major public health concern. Research has focused on developing safer natural products and innovations to meet consumers' acceptance as alternatives to synthetic food preservatives. Many recent novel preservative techniques and applications of both natural and synthetic origin continue to proliferate in food and chemical industries. In particular, some essential oils of plant origin are potent food preservatives and are thus attractive alternatives to synthetic preservatives. This paper provides an overview of recent advances and future prospects in assessing the efficacy of the use of Cymbopogon citratus (lemongrass) essential oil in food preservation. The possible mechanisms of action and toxicological profile as well as evidence for or against the use of this essential oil as an alternative to synthetic food preservatives in domestic and industrial applications are discussed. PMID- 26147359 TI - A practical guideline for the haematological management of major haemorrhage. PMID- 26147360 TI - Risk factors for small bowel bleeding in chronic nonsteroidal anti-inflammatory drug users. AB - OBJECTIVE: The incidence of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced enteropathy is currently increasing. However, the predictors of small bowel bleeding (SBB) associated with NSAIDs are unknown. This study aimed to assess the risk factors of SBB in chronic NSAIDs users. METHODS: We retrospectively compared the medical records of 147 patients receiving NSAIDs in a tertiary-care setting (31 with SBB and 116 without previous bleeding events) and analyzed the predictors of SBB. RESULTS: In total, 31 patients underwent video capsule endoscopy to detect SBB, 74.2% of whom showed the evidence of SBB. Non-invasive treatment was performed in 90.3% of the patients. Multivariate logistic regression analysis revealed that the presence of coronary artery disease [adjusted odds ratio (aOR) 12.43, 95% confidence interval (CI) 1.19-130.34, P = 0.04], use of thienopyridine (aOR 16.93, 95% CI 3.78-75.72, P < 0.001) and prior use of rebamipide (aOR 0.31, 95% CI 0.12-0.82, P = 0.02) were independently associated with SBB in NSAIDs users. CONCLUSIONS: Coronary artery disease and co use of thienopyridine were associated with SBB in NSAIDs users. The patients with coronary artery disease co-using thienopyridine need to be monitored for the occurrence of SBB when they were prescribed with NSAIDs. PMID- 26147361 TI - Do aftercare mental health services reduce risk of psychiatric rehospitalization for children? AB - Appropriate and timely aftercare services are considered critical for children and adolescents with previous psychiatric hospitalization. The purpose of the present study was to investigate the relationship between type and amount of aftercare received and rehospitalization among youths who have been previously hospitalized due to psychiatric illness. The sample consisted of 569 youth ages 6 18 who received services in a large public service system. The sample of youth was 58% female and consisted largely of ethnic minorities (51% Hispanic, 26% White, 16% African American, and 7% were another race/ethnicity). Demographic, diagnostic, and service use data was obtained from billing records. Time dependent Cox regression models evaluated the impact of aftercare (the primary dependent variable of interest) on risk of rehospitalization. Separate models were analyzed for each type of service and all models were adjusted for race/ethnicity, age, gender, diagnosis, insurance status, and comorbid substance use. Seventy percent of youths with a psychiatric hospitalization received aftercare and 28% were rehospitalized within 6 months of discharge. The total hours of services youths received was significantly related to a smaller likelihood of rehospitalization. Having a diagnosis of schizophrenia was associated with a higher risk of rehospitalization and receiving more days of day treatment was associated with a lower risk of rehospitalization. Given the restrictiveness and cost of hospitalization, mental health practitioners should focus on improving access, engagement, and quality of aftercare services. (PsycINFO Database Record PMID- 26147362 TI - Zambian Women in South Africa: Insights Into Health Experiences of Labia Elongation. AB - Labia minora elongation consists in the manual stretching of the inner lips of the external genitalia. This practice is documented in east and southern Africa. The experiences of African women in the diaspora practicing elongation are not thoroughly understood. The purpose of this qualitative study was to explore the health harms and benefits associated with this practice of Zambian women who have migrated to Cape Town, South Africa. Twenty women and seventeen men participated in this study. Between December 2013 and May 2014, in-depth interviews and natural group discussions were conducted with the participants. The focus of this article is to report on the emic of the women related to notions of health, hygiene, and well-being. Labial elongation is perceived as a practice involving minor, short-term adverse effects that can be prevented by following some basic hygiene. Overall, personal and social value is placed on this practice because of its reported benefits for the sexual health of men and women, and for women's femininity and self-image. Further research is necessary on how female genital modifications influence Zambians' sexual preferences to inform the development of culturally appropriate health promotion interventions. PMID- 26147363 TI - Heparin Kinetics: The "Holy Grail" of Periprocedural Anticoagulation for Ablation of Atrial Fibrillation. PMID- 26147364 TI - Overcoming the Body Mass Index as a Barrier in Kidney Transplantation. PMID- 26147365 TI - Individual differences in physiological flexibility predict spontaneous avoidance. AB - People often regulate their emotions by resorting to avoidance, a putatively maladaptive strategy. Prior work suggests that increased psychopathology symptoms predict greater spontaneous utilisation of this strategy. Extending this work, we examined whether heightened resting cardiac vagal tone (which reflects a general ability to regulate emotions in line with contextual demands) predicts decreased spontaneous avoidance. In Study 1, greater resting vagal tone was associated with reduced spontaneous avoidance in response to disgust-eliciting pictures, beyond anxiety and depression symptoms and emotional reactivity. In Study 2, resting vagal tone interacted with anxiety and depression symptoms to predict spontaneous avoidance in response to disgust-eliciting film clips. The positive association between symptoms and spontaneous avoidance was more pronounced among participants with reduced resting vagal tone. Thus, increased resting vagal tone might protect against the use of avoidance. Our findings highlight the importance of assessing both subjective and biological processes when studying individual differences in emotion regulation. PMID- 26147366 TI - Indoleamine 2,3-dioxygenase depletes tryptophan, activates general control non derepressible 2 kinase and down-regulates key enzymes involved in fatty acid synthesis in primary human CD4+ T cells. AB - Indoleamine 2,3-dioxygenase (IDO) is expressed in antigen-presenting cells and exerts immunosuppressive effects on CD4(+) T cells. One mechanism is through the inhibition of aerobic glycolysis. Another prerequisite for T-cell proliferation and differentiation into effector cells is increased fatty acid (FA) synthesis. The effect of IDO on enzymes involved in FA synthesis was evaluated in primary human cells both in mixed lymphocyte reactions in the presence or not of the IDO inhibitor 1-dl-methyl-tryptophan, and in stimulated CD4(+) T cells in the presence or not of the general control non-derepressible 2 (GCN2) kinase activator tryptophanol (TRP). IDO or TRP inhibited cell proliferation. By assessing the level of GCN2 kinase or mammalian target of rapamycin complex 1 substrates along with a kynurenine free system we showed that IDO exerts its effect mainly through activation of GCN2 kinase. IDO or TRP down-regulated ATP citrate lyase and acetyl coenzyme A carboxylase 1, key enzymes involved in FA synthesis. Also, IDO or TRP altered the expression of enzymes that control the availability of carbon atoms for FA synthesis, such as lactate dehydrogenase-A, pyruvate dehydrogenase, glutaminase 1 and glutaminase 2, in a way that inhibits FA synthesis. In conclusion, IDO through GCN2 kinase activation inhibits CD4(+) T cell proliferation and down-regulates key enzymes that directly or indirectly promote FA synthesis, a prerequisite for CD4(+) T-cell proliferation and differentiation into effector cell lineages. PMID- 26147367 TI - Talking About Quitting: Interpersonal Communication as a Mediator of Campaign Effects on Smokers' Quit Behaviors. AB - This study examined the role of interpersonal communication in the context of a mass media anti-smoking campaign. Specifically, it explored whether conversations about campaign ads and/or about quitting mediated campaign exposure effects on 2 quitting behaviors (sought help to quit and tried to quit smoking completely), as well as the relation between ad-related and quitting-related conversations. Data were collected before the campaign and monthly for 16 months during the campaign through cross-sectional telephone surveys among a sample of 3,277 adult Philadelphia smokers. Follow-up interviews were conducted among 877 participants 3 months after their first survey. Cross-sectional and longitudinal mediation models with bootstrap procedures assessed the indirect effects of campaign exposure on outcomes through conversations, and the indirect effects of conversations about ads on outcomes through conversations about quitting. In addition, lagged regression analyses tested the causal direction of associations between the variables of interest. The results partially support hypotheses that conversations about quitting mediate campaign effects on quitting-related behaviors and, in line with previous research, that conversations about the ads have indirect effects on quitting-related behaviors by triggering conversations about quitting. These findings demonstrate the importance of considering interpersonal communication as a route of campaign exposure effects when evaluating and designing future public health campaigns. PMID- 26147368 TI - Life history of the sand fly vector Lutzomyia cruciata in laboratory conditions. AB - Lutzomyia cruciata Coquillet (Diptera: Psychodidae: Phlebotominae) is a potential vector of Leishmania sp.; its geographical distribution in Mexico is widespread, but its life history is unknown. The present study gives relevant information on the life cycle, morphology, survival and reproduction of Lu. cruciata observed over successive generations under laboratory conditions. Seven successive generations were produced. A total of 975 adults were obtained in a sexual proportion of 1.1 : 1 (female : male). Each Lu. cruciata female produced 20.7 eggs and 1.9 adults, approximately, with a proportion of eggs per female of 2.7% (first generation) and 21.3% (second generation). The life cycle of Lu. cruciata, from egg to adult, occurred in 52.7 +/- 0.52 days. The largest percentage of mortality occurred during the egg stage (48.5%) and the first larval instar (26.5%), whereas in the pupal stage mortality was the lowest (9.1%). Lutzomyia cruciata exhibits sexual dimorphism based on size, which is exhibited as of the second larval instar, males being smaller than females. The maximum survival of females and males was 10 and 15 days, respectively. An overview of the immature stages of the species made with an electronic scanning microscope is included. This paper contributes basic information on aspects of Lu. cruciata that were previously unknown related to its life history. PMID- 26147369 TI - Matrix M H5N1 Vaccine Induces Cross-H5 Clade Humoral Immune Responses in a Randomized Clinical Trial and Provides Protection from Highly Pathogenic Influenza Challenge in Ferrets. AB - BACKGROUND AND METHODS: Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. Sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine H5N1 (NIBRG-14) doses (21 days apart) of 30 MUg HA alone or 1.5, 7.5 or 30 MUg HA adjuvanted with Matrix M. The kinetics and longevity of the serological responses against NIBRG 14 were determined by haemagglutination inhibition (HI), single radial haemolysis (SRH), microneutralization (MN) and ELISA assays. The cross-H5 clade responses in sera were determined by HI and the antibody-secreting (ASC) cell ELISPOT assays. The protective efficacy of the vaccine against homologous HPAI challenge was evaluated in ferrets. RESULTS: The serological responses against the homologous and cross-reactive strains generally peaked one week after the second dose, and formulation with Matrix M augmented the responses. The NIBRG-14-specific seroprotection rates fell significantly by six months and were low against cross reactive strains although the adjuvant appeared to prolong the longevity of the protective responses in some subjects. By 12 months post-vaccination, nearly all vaccinees had NIBRG-14-specific antibody titres below the protective thresholds. The Matrix M adjuvant was shown to greatly improve ASC and serum IgG responses following vaccination. In a HPAI ferret challenge model, the vaccine protected the animals from febrile responses, severe weight loss and local and systemic spread of the virus. CONCLUSION: Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate. TRIAL REGISTRATION: ClinicalTrials.gov NCT00868218. PMID- 26147370 TI - daf-41/p23: A Small Protein Heating Up Lifespan Regulation. PMID- 26147371 TI - Modeling of Beta Diversity in Tunisian Waters: Predictions Using Generalized Dissimilarity Modeling and Bioregionalisation Using Fuzzy Clustering. AB - Spatial patterns of beta diversity are a major focus of ecology. They can be especially valuable in conservation planning. In this study, we used a generalized dissimilarity modeling approach to analyze and predict the spatial patterns of beta diversity for commercially exploited, demersal marine species assemblages along the Tunisian coasts. For this study, we used a presence/absence dataset which included information on 174 species (invertebrates and fishes) and 9 environmental variables. We first performed the modeling analyses and assessed beta diversity using the turnover component of the Jaccard's dissimilarity index. We then performed nonmetric multidimensional scaling to map predicted beta diversity. To delineate the biogeographical regions, we used fuzzy cluster analysis. Finally, we also identified a set of indicator species which characterized the species assemblages in each identified biogeographical region. The predicted beta diversity map revealed two patterns: an inshore-offshore gradient and a south-north latitudinal gradient. Three biogeographical regions were identified and 14 indicator species. These results constitute a first contribution of the bioregionalisation of the Tunisian waters and highlight the issues associated with current fisheries management zones and conservation strategies. Results could be useful to follow an Ecosystem Based Management approach by proposing an objective spatial partitioning of the Tunisian waters. This partitioning could be used to prioritize the adjustment of the actual fisheries management entities, identify current data gaps, inform future scientific surveys and improve current MPA network. PMID- 26147372 TI - Cellulite treatment: a comprehensive literature review. AB - An effective and long-term treatment of cellulite has not been well established. To our knowledge, no review has analyzed the whole range of treatments for this condition. We conducted a review of in vivo studies on humans adopting the key words "cellulite" and "treatment." The studies were included according to eligibility criteria. We performed an analysis to estimate the overall effect of cellulite treatments from clinical studies. Medline library was screened up to December 2014 to identify eligible studies. We included 73 original studies in the present review. All of them were clinical studies, in most of them, only women were recruited. Above the studies searched up, 66 tested the effectiveness of an exclusive treatment performed without the association to other procedures: 11 topical agents, 10 shock-wave therapy, 10 radio frequency, eight laser therapy, five oral therapy, four manual massage therapy, three carbon dioxide therapy, two compressive therapy, two infrared therapy, one dermabrasion, and 11 devices that use an association of multiple treatments. Seven papers tested a combination of two or more treatments. The mean difference of clinical morphologic features and ultrastructural changes between the treated group and the controlled showed significant heterogeneity between studies. It is still difficult to indicate an exclusive and effective single treatment for this condition. Our analysis purposed to obtain a complete overview of the available treatments in cellulite reduction. PMID- 26147373 TI - The effectiveness of the newly designed thermal gown on hypothermic patients after spinal surgery. AB - AIMS AND OBJECTIVES: To develop the newly designed thermal gown to test the effectiveness in relieving postoperative hypothermia as compared to traditional cotton cloth. BACKGROUND: Hypothermia is a common problem after spinal surgery. A patient's safety and comfort are significant. Currently, most research is focused on instruments that relieve a patient's hypothermia. Studies have rarely considered a patient's comfort while caring for their body temperature. DESIGN: This study employed an experimental design. The participants were assigned randomly to two groups: the experimental group (N = 50) and the control group (N = 50). METHODS: The experimental group received the newly designed thermal gown intervention. The control group received the standard postanaesthesia care unit re-warming intervention. The material used to collect data included demographic data, postoperative management and comfort level. Nurses measured patients' vital signs and asked for patients' subjective comfort level on admission to the postanaesthesia care unit every 10 minutes until their discharge from the postanaesthesia care unit. RESULT: The accumulated percentage for thermal gown group patients in reaching 36 degrees C during the first 20 minutes of admission was significantly higher than that of the cotton cloth group. The thermal gown group individuals showed significantly higher comfort levels (score = 4) at 10 minutes, when compared to the cotton cloth group. CONCLUSION: Results suggested that the newly designed thermal gown had effectively improved postoperative temperature and comfort level with an evidence-based intervention. RELEVANCE TO CLINICAL PRACTICE: Maintaining a patient's body temperature is a major task for nurses working in the post-anaesthesia care unit. With the newly designed thermal gown, the duration of a patient's stay in the postanaesthesia care unit was shortened and the patient's comfort was increased. PMID- 26147374 TI - Correction: Asymmetric Mating Interference between Two Related Mosquito Species: Aedes (Stegomyia) albopictus and Aedes (Stegomyia) cretinus. PMID- 26147375 TI - Advantages of dual hypothermic oxygenated machine perfusion over simple cold storage in the preservation of liver from porcine donors after cardiac death. AB - AIMS: We have compared hypothermic oxygenated machine perfusion (HOPE) with simple cold storage (SCS) in liver preservation with a porcine model of donor after cardiac death (DCD). METHODS: A DCD model was developed in 10 hybrid pigs by apnea. Livers were harvested after 30 min of warm ischemia (WI) and randomly preserved using HOPE (HOPE group, five pigs, dual perfusion via portal vein and hepatic artery) or SCS (SCS group, five pigs) methods. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, lactic acid, and pyruvic acid were measured by microdialysis analyzer. RESULTS: Histological morphology of liver tissue was significantly affected by 30 min of WI. HOPE significantly delayed histological morphology change and cell apoptosis. Release of ALT and AST was significantly higher in SCS group compared to HOPE group (p < 0.05) during 12-18 h of preservation. Levels of glucose, lactic acid, and pyruvic acid in HOPE group were significantly closer to baseline than that in SCS group after 18 h of preservation (p < 0.05). CONCLUSIONS: HOPE is supported for the preservation of liver from DCD due to significant improvement in the prevention of hepatocellular damage and protection of liver function and metabolic activity compared with SCS. PMID- 26147376 TI - Barriers and facilitators to starting insulin in patients with type 2 diabetes: a systematic review. AB - AIM: To identify the barriers and facilitators to start insulin in patients with type 2 diabetes. METHOD: This was a systematic review. We conducted a systematic search using PubMed, EMBASE, CINAHL and Web of Science (up to 5 June 2014) for original English articles using the terms 'type 2 diabetes', 'insulin', and free texts: 'barrier' or 'facilitate' and 'initiate'. Two pairs of reviewers independently assessed and extracted the data. Study quality was assessed with Qualsyst. RESULTS: A total of 9740 references were identified: 41 full-text articles were assessed for eligibility. Twenty-five articles (15 qualitative, 10 quantitative) were included in the review. Good inter-rater reliability was observed for the Qualsyst score (weighted kappa 0.7). Three main themes identified were as follows: patient-related, healthcare professional and system factors. The main patient-related barriers were fear of pain and injection (n = 18), concerns about side effects of insulin (n = 12), perception that insulin indicated end stage of diabetes (n = 11), inconvenience (n = 10), difficulty in insulin administration (n = 7), punishment (n = 7) and stigma and discrimination (n = 7). Healthcare professionals' barriers were as follows: poor knowledge and skills (n = 9), physician inertia (n = 5) and language barriers (n = 4). System barriers included lack of time (n = 5). The most common facilitators were understanding the benefits of insulin (n = 7), not being afraid of injections (n = 5), and patient education and information (n = 5). CONCLUSION: Major barriers to insulin initiation persist despite availability of newer and safer insulin. Healthcare professionals should explore and address these barriers. Targeted interventions should be developed to overcome these barriers. PMID- 26147377 TI - The chloroplastic DEVH-box RNA helicase INCREASED SIZE EXCLUSION LIMIT 2 involved in plasmodesmata regulation is required for group II intron splicing. AB - INCREASED SIZE EXCLUSION LIMIT 2 (ISE2) encodes a putative DEVH-box RNA helicase originally identified through a genetic screening for Arabidopsis mutants altered in plasmodesmata (PD) aperture. Depletion of ISE2 also affects chloroplasts activity, decreases accumulation of photosynthetic pigments and alters expression of photosynthetic genes. In this work, we show the chloroplast localization of ISE2 and decipher its role in plastidic RNA processing and, consequently, PD function. Group II intron-containing RNAs from chloroplasts exhibit defective splicing in ise2 mutants and ISE2-silenced plants, compromising plastid viability. Furthermore, RNA immunoprecipitation suggests that ISE2 binds in vivo to several splicing-regulated RNAs. Finally, we show that the chloroplast clpr2 mutant (defective in a subunit of a plastidic Clp protease) also exhibits abnormal PD function during embryogenesis, supporting the idea that chloroplast RNA processing is required to regulate cell-cell communication in plants. PMID- 26147378 TI - Production of Cloned Miniature Pigs Expressing High Levels of Human Apolipoprotein(a) in Plasma. AB - High lipoprotein(a) [Lp(a)] levels are a major risk factor for the development of atherosclerosis. However, because apolipoprotein(a) [apo(a)], the unique component of Lp(a), is found only in primates and humans, the study of human Lp(a) has been hampered due to the lack of appropriate animal models. Using somatic cell nuclear transfer (SCNT) techniques, we produced transgenic miniature pigs expressing human apo(a) in the plasma. First, we placed the hemagglutinin (HA)-tagged cDNA of human apo(a) under the control of the beta-actin promoter and cytomegalovirus enhancer, and then introduced this construct into kidney epithelial cells. Immunostaining of cells with anti-HA antibody allowed identification of cells stably expressing apo(a); one of the positive clones was used to provide donor cells for SCNT, yielding blastocysts that expressed apo(a). Immunohistochemical analysis of tissue sections and RT-PCR analysis of total RNA from organs of cloned piglet revealed that apo(a) is expressed in various tissues/organs including heart, liver, kidney, and intestine. More importantly, a transgenic line exhibited a high level (>400 mg/dL) of Lp(a) in plasma, and the transgenic apo(a) gene was transmitted to the offspring. Thus, we generated a human apo(a)-transgenic miniature pig that can be used as a model system to study advanced atherosclerosis related to human disease. The anatomical and physiological similarities between the swine and human cardiovascular systems will make this pig model a valuable source of information on the role of apo(a) in the formation of atherosclerosis, as well as the mechanisms underlying vascular health and disease. PMID- 26147380 TI - Ebola virus disease: societal challenges and new treatments. AB - Ebola virus disease (EVD) is a zoonotic disease that causes severe haemorrhagic fever, with high fatality rates of up to 90% in humans. Today, there is no effective treatment available. Person-to-person transmission occurs through exposure to blood or body fluids, which can threaten other household members and first-line healthcare workers. The first cases of EVD in Guinea were identified on 22 March 2014. It was initially believed that this like previous outbreaks would be self-limiting. However, lack of public health infrastructure, delays in virus detection and late implementation of control interventions contributed to widespread transmission of EVD in a region inexperienced in dealing with the disease. Socio-cultural and economic factors probably also played a key role in the spread of the disease, resulting in the current large-scale outbreak. Some promising candidate treatments for this disease are now being developed. PMID- 26147379 TI - Brief Glutamine Pretreatment Increases Alveolar Macrophage CD163/Heme Oxygenase 1/p38-MAPK Dephosphorylation Pathway and Decreases Capillary Damage but Not Neutrophil Recruitment in IL-1/LPS-Insufflated Rats. AB - BACKGROUND: Glutamine (GLN) attenuates acute lung injury (ALI) but its effect on alveolar macrophages is unknown. We hypothesized that GLN pretreatment would induce the anti-inflammatory CD163/heme oxygenase (HO)-1/p38-MAPK dephosphorylation pathway in alveolar macrophages and reduce ALI in rats insufflated with interleukin-1 (IL-1) and lipopolysaccharide (LPS). METHODS: Male Sprague-Dawley rats were randomized to the following groups: GLN-IL-1/LPS-, GLN+IL-1/LPS-, GLN-IL-1/LPS+, and GLN+IL-1/LPS+. GLN pretreatment was given via gavage (1 g/kg L-alanyl-L-glutamine) daily for 2 days. ALI was subsequently induced by insufflating 50 ng IL-1 followed by 5mg/kg E.coli LPS. After 24h, bronchoalveolar lavage (BAL) protein, lactate dehydrogenase (LDH) and neutrophil concentrations were analyzed. BAL alveolar macrophage CD163+ expression, HO-1 and p38-MAPK concentrations were measured, as well as alveolar macrophage tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 concentrations. Histology and immunofluorescence studies were also performed. RESULTS: Following IL-1/LPS insufflation, GLN pretreated rats had significantly decreased BAL protein and LDH concentrations, but not BAL neutrophil counts, compared to non-GLN pretreated rats. The number of alveolar macrophages and the number of CD163+ macrophages were significantly increased in GLN pretreated IL-1/LPS-insufflated rats compared to non-GLN pretreated, IL-1/LPS-insufflated rats. GLN pretreatment before IL 1/LPS also significantly increased HO-1 concentrations and dephosphorylated p38 MAPK levels but not cytokine levels in alveolar macrophages. Immunofluorescence localized CD163 and HO-1 in alveolar macrophages. CONCLUSION: Short-term GLN pretreatment activates the anti-inflammatory CD163/HO-1/p38-MAPK dephosphorylation pathway of alveolar macrophages and decreases capillary damage but not neutrophil recruitment in IL-1/LPS-insufflated rats. PMID- 26147382 TI - Chronic peroxisome proliferator-activated receptorbeta/delta agonist GW0742 prevents hypertension, vascular inflammatory and oxidative status, and endothelial dysfunction in diet-induced obesity. AB - OBJECTIVE: Endothelial dysfunction plays a key role in obesity-induced risk of cardiovascular disease. The aim of the present study was to analyze the effect of chronic peroxisome proliferator-activated receptor (PPAR)beta/delta agonist GW0742 treatment on endothelial function in obese mice fed a high-fat diet (HFD). METHODS AND RESULTS: Five-week-old male mice were allocated to one of the following groups: control, control-treated (GW0742, 3 mg/kg per day, by oral gavage), HFD, HFD + GW0742, HFD + GSK0660 (1 mg/kg/day, intraperitoneal) or HFD GW0742-GSK0660 and followed for 11 or 13 weeks. GW0742 administration to mice fed HFD prevented the gain of body weight, heart and kidney hypertrophy, and fat accumulation. The increase in plasma levels of fasting glucose, glucose tolerance test, homeostatic model assessment of insulin resistance, and triglyceride found in the HFD group was suppressed by GW0742. This agonist increased plasma HDL in HFD-fed mice and restored the levels of tumor necrosis factor-alpha and adiponectin in fat. GW0742 prevented the impaired nitric oxide-dependent vasodilatation induced by acetylcholine in aortic rings from mice fed HFD. Moreover, GW0742 increased both aortic Akt and endothelial nitric oxide synthase phosphorylation, and inhibited the increase in caveolin-1/endothelial nitric oxide synthase interaction, ethidium fluorescence, NOX-1, Toll-like receptor 4, tumor necrosis factor-alpha, and interleukin-6 expression, and IkappaBalpha phosphorylation found in aortae from the HFD group. GSK0660 prevented all changes induced by GW0742. CONCLUSION: PPARbeta/delta activation prevents obesity and exerts protective effects on hypertension and on the early manifestations of atherosclerosis, that is, endothelial dysfunction and the vascular pro-oxidant and pro-inflammatory status, in HFD-fed mice. PMID- 26147381 TI - Maternal Vitamin D Status and Its Related Factors in Pregnant Women in Bangkok, Thailand. AB - BACKGROUND: There are few data focusing on the prevalence of vitamin D deficiency in tropical countries. OBJECTIVES: We determined the vitamin D status in pregnant women and examined the factors associated with vitamin D deficiency. DESIGN AND METHODS: A cross-sectional study of 147 pregnant Thai women aged 18-45 years at Siriraj Hospital (a university hospital in Bangkok, Thailand) was undertaken. Clinical data and plasma levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), calcium, albumin, phosphate and magnesium were obtained in pregnant women at delivery. RESULTS: The prevalence of hypovitaminosis D [defined as 25(OH)D <75 nmol/L] in pregnant women at delivery was 75.5% (95% confidence interval (CI), 67.7-82.2%). Of these, vitamin D insufficiency [defined as 25(OH)D 50-74.9 nmol/L] was found in 41.5% (95% CI, 33.4-49.9%) and vitamin D deficiency [25(OH)D <50 nmol/L] was found in 34.0% (95% CI, 26.4-42.3%) of women. The mean 25(OH)D concentration was 61.6 +/- 19.3 nmol/L. The correlation between 25(OH)D and iPTH was weak (r = -0.29, P<0.01). Factors associated with vitamin D deficiency by multiple logistic regression were: pre-pregnancy body mass index (BMI in kg/m2, odds ratio (OR), 0.88, 95% CI 0.80-0.97, P = 0.01) and season of blood collection (winter vs. rainy, OR, 2.62, 95% CI 1.18-5.85, P = 0.02). CONCLUSIONS: Vitamin D deficiency is common among pregnant Thai women. The prevalence of vitamin D deficiency increased in women who had a lower pre-pregnancy BMI and whose blood was collected in the winter. Vitamin D supplementation may need to be implemented as routine antenatal care. PMID- 26147383 TI - Effects of 2-year vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly on arterial stiffness and cardiovascular outcomes within the B-PROOF trial. AB - INTRODUCTION: Hyperhomocysteinemia is an important cardiovascular risk indicator in the oldest old, and is associated with elevated arterial stiffness in this age group. Since several intervention trials reported a lack of benefit of B-vitamin supplementation on cardiovascular outcomes, we aimed to investigate the effect of B-vitamin supplementation on arterial stiffness and atherosclerosis in hyperhomocysteinemic elderly patients. METHODS: The B-PROOF study is a double blind, randomized controlled trial, including 2919 elderly aged at least 65 years, with hyperhomocysteinemia (12-50 MUmol/l), treated with B-vitamins (500 MUg vitamin B12 and 400 MUg folic acid) or placebo for 2 years. In a subgroup (n = 569), the effect of B-vitamins on pulse wave velocity (PWV) was investigated as a measurement of arterial stiffness. To measure atherosclerosis, carotid intima media thickness (IMT) measures had been used. Incidents of cardiovascular and cerebrovascular events were determined via structured questionnaires, and blood pressure was also measured. RESULTS: Compared to placebo, B-vitamin supplementation lowered serum homocysteine by 3.6 MUmol/l (P < 0.001). Analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline. Furthermore, no effect on carotid IMT was observed. DISCUSSION: Vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly patients have no effect on PWV or carotid IMT. Further research will still be necessary to unravel the effects and pathways of homocysteine-lowering treatment on cardiovascular outcomes. PMID- 26147384 TI - Exome sequencing in seven families and gene-based association studies indicate genetic heterogeneity and suggest possible candidates for fibromuscular dysplasia. AB - BACKGROUND: Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, aneurysm and dissection, mainly of renal arteries and carotids. FMD occurs predominantly in women with nearly four out of 1000 prevalence and cause hypertension, renal ischemia or stroke. The pathogenesis of FMD is unknown and a genetic origin is suspected given its demonstrated familial aggregation. METHOD: We performed whole exome sequencing (WES) in 16 cases (seven families). Coding variants in 3971 genes were prioritized on frequency (minor allele frequency < 0.01) and in silico predicted functionality. RESULTS: No gene harbours variants that are shared among all affected members of at least three families. Variants from 16 genes of vascular and connective tissue diseases are excluded as causative in these families. Genes with at least four variants in the 16 patients and vascular genes were followed-up using genotypes from 249 unrelated cases and 689 controls. Gene-based association analyses using SKAT-O shows nominal significant association with multifocal FMD (N = 164) for myosin light chain kinase (MYLK, P = 0.01) previously involved in thoracic aortic aneurysm, obscurin (OBSCN), a sarcomeric protein (P = 0.003), dynein cytoplasmic heavy chain 1 (DYNC2H1, P = 0.02) and RNF213 previously associated with Moyamoya disease (P = 0.01). CONCLUSION: Our study indicates genetic heterogeneity and the unlikely existence of a major gene for FMD and excludes the role of several vascular genes in familial FMD. We also suggest four possible candidate genes for multifocal FMD, though these findings need further genetic and functional confirmation. More powerful WES and association studies [e.g. genome-wide association study (GWAS)] will better decipher the genetic basis of FMD. PMID- 26147385 TI - Carotid-femoral pulse wave velocity assessment by two different methods: implications for risk assessment. AB - INTRODUCTION: Several devices are available for carotid-femoral pulse wave velocity (cfPWV) measurement, and a cut-off value for reference cfPWV has been established. However, discrepancies between devices have been reported. OBJECTIVES: The aim of the study was to establish the concordance of two common techniques (Complior and SphygmoCor), taking into account the anatomical distance between the measurement sites, and to investigate the impact on cardiovascular risk stratification. METHODS: cfPWV, central and peripheral blood pressure were assessed in patients attending the hypertension outpatient clinic. The subtracted carotid-femoral distance was estimated both according to the manufacturer's recommendations and correcting the obtained values by 10.3%. Bland-Altman plots, Pearson's correlation coefficient, Lin's concordance correlation coefficient and multivariate models were used to investigate the difference in cfPWV. RESULTS: cfPWV assessed in 118 patients (age 55 +/- 12 years, 61% hypertensive patients, BMI 28.9 +/- 4.4 kg/m2) with the Complior device was lower than that assessed with the SphygmoCor device, regardless of correcting the subtracted carotid femoral distance (8.7 vs. 10.3 m/s and 9.3 m/s, respectively; P value < 0.001). The average difference was -1.59 +/- 1.5 and -0.617 +/- 1.39 m/s for corrected and uncorrected SphygmoCor values, respectively, SBP, BMI and female being the main determinants of the difference. Cardiovascular risk stratification changed in up to 40% of the study population, depending on the device and the arterial distance estimation. CONCLUSION: The concordance between the Complior and the SphygmoCor device is poor when the anatomical artery length is controlled for and in the presence of cardiovascular risk factors, resulting in a difference in classification of cardiovascular risk. PMID- 26147386 TI - Aortic stiffness is associated with elevated high-sensitivity cardiac troponin T concentrations at a chronic stage after ST-segment elevation myocardial infarction. AB - OBJECTIVES: Aortic pulse wave velocity (PWV)--the proposed gold standard for the assessment of aortic stiffness--is a major determinant of left ventricular after load and coronary perfusion. We aimed to investigate the association between aortic PWV and subclinical elevation of high-sensitivity cardiac troponin T (hs TnT) concentrations at a chronic stage after acute ST-segment elevation myocardial infarction (STEMI). METHODS: Seventy-four patients with acute STEMI were included in this cross-sectional single-centre study at the University Hospital of Innsbruck. All patients underwent cardiac MRI for the assessment of left ventricular function, morphology, infarct size and aortic PWV 12 months after acute STEMI. Blood samples were drawn at 12 months by peripheral venipuncture. Levels of hs-TnT were measured by a commercially available immunoassay (Roche Diagnostics). RESULTS: hs-TnT levels (6.4 ng/l, inter-quartile range 5.0-8.6) were significantly associated with age (r = 0.417, P < 0.001), plasma creatinine levels (r = 0.257, P = 0.027), high-sensitivity C-reactive protein levels (r = 0.281, P = 0.015) and aortic PWV (r = 0.435, P < 0.001). Multiple linear regression analysis revealed aortic PWV (beta = 0.330, P = 0.025), apart from plasma creatinine concentrations (beta = 0.279, P = 0.010), to be independently associated with hs-TnT concentrations (model: R = 0.597, P < 0.001). CONCLUSION: The present study showed an association of aortic stiffness and hs-TnT concentrations at a chronic stage after STEMI. PMID- 26147387 TI - Prehypertension prior to or during early pregnancy is associated with increased risk for hypertensive disorders in pregnancy and gestational diabetes. AB - OBJECTIVE: To examine whether and to what extent pre/early-pregnancy blood pressure (BP) in the prehypertensive range contributes to the development of hypertensive disorders in pregnancy and gestational diabetes mellitus (GDM). METHODS: The cohort consisted of women who had their prenatal care and delivered a live singleton neonate at the Kaiser Permanente Bellflower Medical Center during 2005-2010. Women with prepregnancy hypertension (HTN) were excluded from the analysis. Among the remaining women, pre/early-pregnancy prehypertension (preHTN) was defined as two consecutive elevated BPs (SBP >= 120 or DBP >= 80) at separate ambulatory visits in the period from 1 year prior to pregnancy through the first trimester. Hypertensive disorders of pregnancy, including pre eclampsia/eclampsia (PE/E), were identified by ICD-9 diagnoses. Mid-pregnancy 75 g oral glucose tolerance tests were used to identify GDM. Multivariable logistic and robust Poisson regression was used to test the association between preHTN and each outcome, adjusted for potential confounders. RESULTS: Among 7802 women with at least two BP measures prior to or early in pregnancy, 2156 (27.6%) had preHTN. Overall, 653 (8.4%) developed a hypertensive disorder of pregnancy, 373 (4.8%) had PE/E, and 1877 (24.1%) developed GDM. After covariate adjustment, women with preHTN were 2.65 [95% confidence interval (CI) 2.22-3.16], 2.17 (95% CI 1.72 2.73), and 1.20 (95% CI 1.09-1.33) times as likely to develop any hypertensive disorder, PE/E, and GDM, respectively, compared to normotensive women. CONCLUSION: Prospective studies aimed at evaluating whether women with preHTN detected prior to or early in pregnancy may benefit from more intensive screening and/or interventions to prevent hypertensive disorders in pregnancy and GDM are needed. PMID- 26147388 TI - Assessment of systolic aortic pressure and its association to all cause mortality critically depends on waveform calibration. AB - BACKGROUND: The aim of this study is the prospective investigation of the association of brachial SBP (bSBP) and aortic SBP (aSBP) to all-cause mortality, with special emphasis on different calibration methods for central pressure estimates, in particular, brachial systolic and diastolic, as well as brachial mean and diastolic pressures. METHOD: One hundred and fifty-nine patients were enrolled in a longitudinal, prospective study of arterial stiffness and cardiovascular risk in a chronic kidney disease stages 2-4 cohort. Office measurements of bSBP and aSBP were assessed by a validated oscillometric device. Prognostic factors of survival were identified by use of Cox proportional-hazards regression models. RESULTS: After a mean follow-up duration of 42 months (range 30-50 months), 13 patients died. In univariate Cox analysis, bSBP and aSBP calibrated using bSBP and bDBP did not significantly predict mortality, only aSBP assessed using measured mean and diastolic pressure calibration was significantly associated with mortality (hazard ratio 1.027, P = 0.008). This remained significant in multivariate analysis after adjustment for age, sex, and anthropometric measures. More important, adding bSBP to the multivariate model (hazard ratio 0.91, P = 0.003) lead to a significantly increased prognostic power of aortic systolic pressure (hazard ratio 1.097, P < 0.001) and indicated that differences between bSBP and aSBP are of potential interest. CONCLUSION: Within our cohort, only aSBP assessed with measured mean and diastolic pressure independently predicted mortality and provided additional prognostic value on top of bSBP readings. Therefore, the method of calibration plays an important role for predictive power of aSBP. PMID- 26147389 TI - The utility of renal venous renin studies in selection of patients with renal artery stenosis for angioplasty: a retrospective study. AB - OBJECTIVES: Recent studies of renal artery stenosis (RAS) failed to demonstrate greater benefit from angioplasty in terms of blood pressure (BP) lowering than medical treatment. Not all RAS are haemodynamically significant and identification of patients likely to benefit from angioplasty remains essential. METHODS: We examined whether performing renal venous renin studies under stringent conditions might predict BP improvement. Patients with at least 60% RAS who underwent renal venous renin measurements in 2008-2013 were identified. Renal venous renin lateralization ratios (RVRRs) were calculated by dividing venous renin from the stenotic kidney with contralateral levels before and after stimulation with enalaprilat or captopril. Benefit was defined as BP less than 140/90 mmHg without medication, 10% decreased mean BP without increased daily defined doses (DDDs) or decreased DDD without a significant increase of mean BP. RESULTS: Twenty-eight patients were treated medically and 42 with angioplasty (median age 60.1 years, 41% male, 29% chronic kidney disease, 50% resistant hypertension). At 11.4 +/- 3.3 months, 69% of patients treated with angioplasty had BP benefit compared with 25% with medical treatment (P < 0.001). Logistic regression identified resistant hypertension [odds ratio (OR) 0.18, 95% confidence interval (95% CI) 0.04-0.82, P = 0.03] and baseline DDD (OR 0.69, 95% CI 0.48-0.98, P = 0.04) as being negatively associated, and positive stimulated RVRR (OR 21.6, 95% CI 3.50-133.3, P = 0.001) positively associated with benefit from angioplasty. On multivariate logistic regression, only stimulated RVRR positivity predicted BP benefit (OR 20.5, 95% CI 2.9-145.0, P = 0.003). CONCLUSION: These findings suggest that a positive stimulated RVRR measured under optimal conditions may help to identify patients with RAS likely to improve from angioplasty. PMID- 26147390 TI - A Transmembrane Domain GGxxG Motif in CD4 Contributes to Its Lck-Independent Function but Does Not Mediate CD4 Dimerization. AB - CD4 interactions with class II major histocompatibility complex (MHC) molecules are essential for CD4+ T cell development, activation, and effector functions. While its association with p56lck (Lck), a Src kinase, is important for these functions CD4 also has an Lck-independent role in TCR signaling that is incompletely understood. Here, we identify a conserved GGxxG motif in the CD4 transmembrane domain that is related to the previously described GxxxG motifs of other proteins and predicted to form a flat glycine patch in a transmembrane helix. In other proteins, these patches have been reported to mediate dimerization of transmembrane domains. Here we show that introducing bulky side chains into this patch (GGxxG to GVxxL) impairs the Lck-independent role of CD4 in T cell activation upon TCR engagement of agonist and weak agonist stimulation. However, using Forster's Resonance Energy Transfer (FRET), we saw no evidence that these mutations decreased CD4 dimerization either in the unliganded state or upon engagement of pMHC concomitantly with the TCR. This suggests that the CD4 transmembrane domain is either mediating interactions with an unidentified partner, or mediating some other function such as membrane domain localization that is important for its role in T cell activation. PMID- 26147391 TI - Novel hexapeptide interacts with tubulin and microtubules, inhibits Abeta fibrillation, and shows significant neuroprotection. AB - Herein, we report a novel hexapeptide, derived from activity dependent neuroprotective protein (ADNP), that spontaneously self-assembles to form antiparallel beta-sheet structure and produces nanovesicles under physiological conditions. This peptide not only strongly binds with beta-tubulin in the taxol binding site but also binds with the microtubule lattice in vitro as well as in intracellular microtubule networks. Interestingly, it shows inhibition of amyloid fibril formation upon co-incubation with Abeta peptide following an interesting mechanistic pathway and excellent neuroprotection in PC12 cells treated with anti nerve growth factor (NGF). The potential of this hexapeptide opens up a new paradigm in design and development of novel therapeutics for AD. PMID- 26147392 TI - Weight Watching and the Effect of Landscape on Honeybee Colony Productivity: Investigating the Value of Colony Weight Monitoring for the Beekeeping Industry. AB - Over the last few decades, a gradual departure away from traditional agricultural practices has resulted in alterations to the composition of the countryside and landscapes across Europe. In the face of such changes, monitoring the development and productivity of honey bee colonies from different sites can give valuable insight on the influence of landscape on their productivity and might point towards future directions for modernized beekeeping practices. Using data on honeybee colony weights provided by electronic scales spread across Denmark, we investigated the effect of the immediate landscape on colony productivity. In order to extract meaningful information, data manipulation was necessary prior to analysis as a result of different management regimes or scales malfunction. Once this was carried out, we were able to show that colonies situated in landscapes composed of more than 50% urban areas were significantly more productive than colonies situated in those with more than 50% agricultural areas or those in mixed areas. As well as exploring some of the potential reasons for the observed differences, we discuss the value of weight monitoring of colonies on a large scale. PMID- 26147393 TI - Complete resolution of refractory cutaneous arteritis by intravenous cyclophosphamide pulse therapy. PMID- 26147395 TI - Expanding the role for psychology in addressing environmental challenges. AB - Environmental challenges, though daunting, present an important area for psychologists to apply their knowledge. Psychological theories, research methods, and interventions are essential for examining the questions about human impacts, tendencies, and capacities that are integral to constructing effective responses to these challenges. Although a great deal of relevant research has been done, there is scope for psychologists to be more extensively involved. Following a brief review of existing research, we outline some important new directions. We also highlight 2 key divergences, arguing that psychological research needs to expand beyond a traditional, theory-based and decontextualized approach to environmental issues to incorporate a contextualized or "place-based" approach and a willingness to collaborate in interdisciplinary research teams that focus on specific environmental problems. Suggestions for promoting such interdisciplinary collaborations are reviewed. We encourage psychologists to expand their engagement with important environmental issues through multiple research approaches in order to further their understanding of human behavior, contributions to human well-being, and relevance to other disciplines and to society. PMID- 26147394 TI - The Topoisomerase 1 Inhibitor Austrobailignan-1 Isolated from Koelreuteria henryi Induces a G2/M-Phase Arrest and Cell Death Independently of p53 in Non-Small Cell Lung Cancer Cells. AB - Koelreuteria henryi Dummer, an endemic plant of Taiwan, has been used as a folk medicine for the treatment of hepatitis, enteritis, cough, pharyngitis, allergy, hypertension, hyperlipidemia, and cancer. Austrobailignan-1, a natural lignan derivative isolated from Koelreuteria henryi Dummer, has anti-oxidative and anti cancer properties. However, the effects of austrobailignan-1 on human cancer cells have not been studied yet. Here, we showed that austrobailignan-1 inhibited cell growth of human non-small cell lung cancer A549 and H1299 cell lines in both dose- and time-dependent manners, the IC50 value (48 h) of austrobailignan-1 were 41 and 22 nM, respectively. Data from flow cytometric analysis indicated that treatment with austrobailignan-1 for 24 h retarded the cell cycle at the G2/M phase. The molecular event of austrobailignan-1-mediated G2/M phase arrest was associated with the increase of p21Waf1/Cip1 and p27Kip1 expression, and decrease of Cdc25C expression. Moreover, treatment with 100 nM austrobailignan-1 for 48 h resulted in a pronounced release of cytochrome c followed by the activation of caspase-2, -3, and -9, and consequently induced apoptosis. These events were accompanied by the increase of PUMA and Bax, and the decrease of Mcl-1 and Bcl-2. Furthermore, our study also showed that austrobailignan-1 was a topoisomerase 1 inhibitor, as evidenced by a relaxation assay and induction of a DNA damage response signaling pathway, including ATM, and Chk1, Chk2, gammaH2AX phosphorylated activation. Overall, our results suggest that austrobailignan-1 is a novel DNA damaging agent and displays a topoisomerase I inhibitory activity, causes DNA strand breaks, and consequently induces DNA damage response signaling for cell cycle G2/M arrest and apoptosis in a p53 independent manner. PMID- 26147396 TI - Creating a climate for ergonomic changes in the construction industry. AB - BACKGROUND: Ergonomic solutions that have gained acceptance in other industries are often considered not applicable to a construction work environment, even though the industry is characterized by high physical work demands. METHODS: We conducted 50 key informant interviews with 23 contractor representatives and 27 union staff, plus 4 focus groups with a total of 48 workers. RESULTS: Many workers hold the belief that WMSDs are inevitable as part of the job, and did not consistently believe that changing the nature of the work could prevent that injury or pain. The interviewees reported limited availability and accessibility of tested and effective tools that both reduce physical demand and also get the job done efficiently and effectively. Yet for each major obstacle to implementation of ergonomics in the industry identified, the construction professionals we interviewed offered a variety of solutions. CONCLUSIONS: Contractors, unions, and workers need to work together to find actions that work within the parameters of the current economic environment. PMID- 26147397 TI - Parental involvement, adolescents' self-determined learning and academic achievement in Urban China. AB - Self-determined learning is essential to academic success. The motivational resources development model argues that parents promote academic success in their children indirectly by nurturing self-determined learner. In this study, applying a structural equation modelling and using data collected from 8th graders in Zhuhai, China (n = 1009) in 2012, we aim to answer 2 research questions: (a) What forms of parental involvement are highly correlated with self-determined learning and (b) Can self-determined learning fully mediate the relationship between parental involvement and students' academic performance? We find that parental leisure involvement is positively and significantly associated with the development of self-determined learning, which in turn is significantly and positively correlated with academic achievement. Parental provision of structure or parental academic assistance is not significantly associated with students' self-regulation and students' academic achievement. PMID- 26147398 TI - Asymmetric Total Synthesis of Indole Alkaloids Containing an Indoline Spiroaminal Framework. AB - The total synthesis of the indole alkaloids, neoxaline, oxaline and meleagrin A, all containing a unique indoline spiroaminal framework, was accomplished through the stereoselective introduction of a reverse prenyl group to the congested benzylic carbon of furoindoline, a two-pot transformation of indoline (containing three nitrogen atoms at appropriate positions) to the featured indoline spiroaminal framework, and elimination of carbonate assisted by the adjacent imidazole moiety to construct the (E)-dehydrohistidine. The absolute stereochemistry of neoxaline was elucidated through our total synthesis. In addition, we evaluated the bioactivity, especially the anti-infectious properties, of neoxaline and oxaline, and of some synthetic intermediates. PMID- 26147399 TI - Surface enhanced Raman scattering by graphene-nanosheet-gapped plasmonic nanoparticle arrays for multiplexed DNA detection. AB - We have developed a new type of surface enhanced Raman scattering (SERS) substrate with thiolated graphene oxide (tGO) nanosheets sandwiched between two layers of closely packed plasmonic nanoparticles. The trilayered substrate is built up through alternative loading of interfacially assembled plasmonic nanoparticle arrays and tGO nanosheets, followed by coating the nanoparticle surfaces with poly(ethylene glycol) (PEG). Here tGO plays multifunctional roles as a 2D scaffold to immobilized interfacially assembled plasmonic nanoparticles, a nanospacer to create SERS-active nanogaps between two layers of nanoparticle arrays, and a molecule harvester to enrich molecules of interest viapi-pi interaction. In particular, the molecule harvesting capability of the tGO nanospacer and the stealth properties of PEG coating on the plasmonic nanoparticles collectively lead to preferential positioning of selective targets such as aromatic molecules and single-stranded DNA at the SERS-active nanogap hotspots. We have demonstrated that an SERS assay based on the PEGylated trilayered substrate, in combination with magnetic separation, allows for sensitive, multiplexed "signal-off" detection of DNA sequences of bacterial pathogens. PMID- 26147401 TI - Information Sharing Preferences of Older Patients and Their Families. AB - IMPORTANCE: Elderly patients often share control of their personal health information and decision making with family and friends when needed. Patient portals can help with information sharing, but concerns about privacy and autonomy of elderly patients remain. Health systems that implement patient portals would benefit from guidance about how best to implement access to portals for caregivers of elderly patients. OBJECTIVE: To identify how patients older than 75 years (hereinafter, elders) and family caregivers of such patients approach sharing of health information, with the hope of applying the results to collaborative patient portals. DESIGN, SETTING, AND PARTICIPANTS: A qualitative study was conducted from October 20, 2013, to February 16, 2014, inviting participants older than 75 years (n = 30) and participants who assist a family member older than 75 years (n = 23) to 1 of 10 discussion groups. Participants were drawn from the Information Sharing Across Generations (InfoSAGE) Living Laboratory, an ongoing study of information needs of elders and families based within an academically affiliated network of senior housing in metropolitan Boston, Massachusetts. Groups were separated into elders and caregivers to allow for more detailed discussion. A professional moderator led groups using a discussion guide. Group discussions were audiotaped, transcribed, and analyzed inductively using immersion/crystallization methods for central themes. MAIN OUTCOMES AND MEASURES: Central themes regarding sharing of health information between elderly patients and family caregivers. RESULTS: Seven lessons emerged from 2 main themes. First, sharing information has consequences: (1) elders and caregivers have different perspectives on what is seen as the "burden" of information, (2) access to medical information by families can have unintended consequences, and (3) elders do not want to feel "spied on" by family. Second, control of information sharing is dynamic: (4) elders wish to retain control of decision making as long as possible, (5) transfer of control occurs gradually depending on elders' health and functional status, (6) control of information sharing and decision making should be fluid to maximize elders' autonomy, and (7) no "one-size-fits-all" approach can satisfy individuals' different preferences. CONCLUSIONS AND RELEVANCE: Information sharing and control are complex issues even under the most well-meaning circumstances. While elders may delegate control and share information with family, they want to retain granular control of their information. When using patient portals, simple proxy access may not adequately address the needs and concerns of aging patients. PMID- 26147402 TI - Metabolic Burden and Disease and Mortality Risk Associated with Impaired Fasting Glucose in Elderly Adults. AB - OBJECTIVES: To examine whether impaired fasting glucose (IFG) represents an intermediary condition between normal fasting glucose and diabetes mellitus and, specifically, whether elderly adults with IFG have higher disease burden, cardiovascular risk, and systemic inflammation and higher 2-year mortality and incident disease. DESIGN: Prospective observational study. SETTING: Population derived cohort. PARTICIPANTS: Individuals with a mean age of 78.6 +/- 4.7 (N = 945). MEASUREMENTS: Disease was ascertained using a standardized questionnaire at baseline and 2 years. Fasting metabolic, inflammatory, and oxidative metabolism markers were measured. Disease prevalence, cardiovascular risk, and biochemical markers were compared to determine disease burden and metabolic disturbances in IFG. Adjusted odds ratios (ORs) for 2-year all-cause mortality and incident disease were determined. RESULTS: IFG prevalence was 41%. Individuals with IFG had higher baseline rates of heart disease than those with normal fasting glucose (NFG), similar to that in individuals with diabetes mellitus. IFG was characterized by higher inflammatory markers and oxidative metabolism end products and was an intermediary between NFG and diabetes mellitus for triglycerides and malondialdehyde. Discriminant analysis showed that IFG was independently associated with stroke and higher triglycerides and oxidative stress. Two-year all-cause mortality was 3.9%. The 2-year adjusted ORs for all cause mortality, incident cardiac disease, stroke, and cancer were similar between IFG and NFG, using both American Diabetes Association and World Health Organization IFG criteria. IFG did not predict secondary cardiac events, stroke, or cancer. CONCLUSION: IFG was an intermediary condition for heart disease, inflammation, and oxidative stress in elderly adults but not for 2-year incident disease or all-cause mortality. Longer-term prospective studies are needed to clarify whether IFG in elderly adults portends greater morbidity and mortality. PMID- 26147403 TI - Combinations of the Ghd7, Ghd8 and Hd1 genes largely define the ecogeographical adaptation and yield potential of cultivated rice. AB - Rice cultivars have been adapted to favorable ecological regions and cropping seasons. Although several heading date genes have separately made contributions to this adaptation, the roles of gene combinations are still unclear. We employed a map-based cloning approach to isolate a heading date gene, which coordinated the interaction between Ghd7 and Ghd8 to greatly delay rice heading. We resequenced these three genes in a germplasm collection to analyze natural variation. Map-based cloning demonstrated that the gene largely affecting the interaction between Ghd7 and Ghd8 was Hd1. Natural variation analysis showed that a combination of loss-of-function alleles of Ghd7, Ghd8 and Hd1 contributes to the expansion of rice cultivars to higher latitudes; by contrast, a combination of pre-existing strong alleles of Ghd7, Ghd8 and functional Hd1 (referred as SSF) is exclusively found where ancestral Asian cultivars originated. Other combinations have comparatively larger favorable ecological scopes and acceptable grain yield. Our results indicate that the combinations of Ghd7, Ghd8 and Hd1 largely define the ecogeographical adaptation and yield potential in rice cultivars. Breeding varieties with the SSF combination are recommended for tropical regions to fully utilize available energy and light resources and thus produce greater yields. PMID- 26147405 TI - [ A (no) small sting -- needle phobic patients and medicine]. PMID- 26147406 TI - [News from international literature]. PMID- 26147404 TI - Cyclometalated Iminophosphorane Gold(III) and Platinum(II) Complexes. A Highly Permeable Cationic Platinum(II) Compound with Promising Anticancer Properties. AB - New organometallic gold(III) and platinum(II) complexes containing iminophosphorane ligands are described. Most of them are more cytotoxic to a number of human cancer cell lines than cisplatin. Cationic Pt(II) derivatives 4 and 5, which differ only in the anion, Hg2Cl6(2-) or PF6(-) respectively, display almost identical IC50 values in the sub-micromolar range (25-335-fold more active than cisplatin on these cell lines). The gold compounds induced mainly caspase independent cell death, as previously reported for related cycloaurated compounds containing IM ligands. Cycloplatinated compounds 3, 4, and 5 can also activate alternative caspase-independent mechanisms of death. However, at short incubation times cell death seems to be mainly caspase dependent, suggesting that the main mechanism of cell death for these compounds is apoptosis. Mercury-free compound 5 does not interact with plasmid (pBR322) DNA or with calf thymus DNA. Permeability studies of 5 by two different assays, in vitro Caco-2 monolayers and a rat perfusion model, have revealed a high permeability profile for this compound (comparable to that of metoprolol or caffeine) and an estimated oral fraction absorbed of 100%, which potentially makes it a good candidate for oral administration. PMID- 26147407 TI - [Adjuvants in modern anesthesia - magnesium]. AB - Magnesium plays a key role in many cellular functions and there is growing interest in its role in perioperative medicine. While experimental studies provided promising results for several disease states, clinical trials mainly gave conflicting results. This review article summarizes current knowledge on the homeostasis of magnesium as well as on its proposed indications and recommendations in the clinical setting. PMID- 26147408 TI - [Case report: patient with needle phobia for caesarean section - not quite as in a textbook ...]. AB - In a 20-year old parturient general anesthesia is induced by inhalation and without venous access because of severe needle phobia. This article discusses risks associated with inhalational induction of anesthesia in this special situation. It deals with needle phobia, an anxiety disorder belonging to the group of blood-injury-injection phobia. This psychic illness can cause severe problems for the anaesthetic management in acute or in elective situations. PMID- 26147409 TI - [Cooperation between emergency and forensic medicine - retrospective evaluation of pre-hospital emergency measures]. AB - Emergency medical research is subject to special conditions. Emergency patients e.g. are generally considered to be non-capable of giving consent. This results in sparse emergency medical data when compared to clinical observation studies under controlled conditions. After emergency medical treatment, deceased patients are not rarely subject to forensic investigation. The cooperation between emergency and forensic medicine has not only emergency medical training potential in individual cases, but also scientific innovation potential especially with respect to the retrospective evaluation of pre-hospital emergency measures. Such partnerships (like in Berlin at the Charite - Universitatsmedizin Berlin between the Institute of Legal Medicine and the Center for Musculoskeletal Surgery or in Hamburg between the Institute for Legal Medicine at the University Hospital and the Municipal Fire Brigade with the Emergency Medical Service) are yet exceptional in Germany. PMID- 26147410 TI - [Pssst ... AINS secrets! - today from general and vascular surgery ]. PMID- 26147411 TI - [The addicted patient in anesthesia -- recognizing and prevent risks]. PMID- 26147412 TI - [The addicted patient in anaesthesia -screening, diagnosis and treatment of alcohol use disorders]. AB - Patients consuming > 60g/d of alcohol (e.g. 1.5l of beer), are 2-5 times more likely to suffer post-operative complications such as infectious, bleeding or cardiac complications or an alcohol withdrawal syndrome. By screening and a systematic evaluation risk patients can be identified that may benefit from interventions such as counseling, brief interventions, abstinence, tailored anesthesia, prophylactic treatment of withdrawal symptoms, stress reduction, harm reduction, psychosocial therapy, addiction therapy, multidisciplinary treatment. PMID- 26147413 TI - [The addicted patient in anaesthesia - benzodiazepine dependence]. AB - As a result of the demographic change, the proportions of elderly patients undergoing operations and anesthesia are increasingly important. The consumption of benzodiazepines evidently rises with increasing age. Associated with the increasing consumption in the elderly is the risk of cognitive impairment, delirium, falls and fractures. Also long-term benzodiazepine use in low-dose may induce perioperative withdrawal syndrome. The following article will present characteristics and complications accompanied by critical benzodiazepine use especially in the elderly patients. PMID- 26147414 TI - [The addicted patient in anaesthesia - benzodiazepine dependence]. AB - As a result of the demographic change, the proportions of elderly patients undergoing operations and anesthesia are increasingly important. The consumption of benzodiazepines evidently rises with increasing age. Associated with the increasing consumption in the elderly is the risk of cognitive impairment, delirium, falls and fractures. Also long-term benzodiazepine use in low-dose may induce perioperative withdrawal syndrome. The following article will present characteristics and complications accompanied by critical benzodiazepine use especially in the elderly patients. PMID- 26147415 TI - [Internet, law, personnel & company]. PMID- 26147417 TI - [Industrial forum]. PMID- 26147418 TI - Ionic liquid based lithium battery electrolytes: fundamental benefits of utilising both TFSI and FSI anions? AB - Several IL based electrolytes with an imidazolium cation (EMI) have been investigated trying to elucidate a possible beneficial effect of mixing FSI and TFSI anions in terms of physico-chemical properties and especially Li(+) solvation. All electrolytes were evaluated in terms of phase transitions, densities and viscosities, thermal stabilities, ionic conductivities and local structure, i.e. charge carriers. The electrolytes with up to 20% of Li-salts showed to be promising for high temperature lithium ion battery application (ca. 100 degrees C) and a synergetic effect of having mixed anions is discernible with the LiTFSI0.2EMIFSI0.8 electrolyte giving the best overall performance. The determination of the charge carriers revealed the SN to be ca. 2 for all analysed electrolytes, and proved the analysis of the mixed anion electrolytes to be challenging and inherently leads to an ambiguous picture of the Li(+) solvation. PMID- 26147419 TI - Natural Gas Residual Fluids: Sources, Endpoints, and Organic Chemical Composition after Centralized Waste Treatment in Pennsylvania. AB - Volumes of natural gas extraction-derived wastewaters have increased sharply over the past decade, but the ultimate fate of those waste streams is poorly characterized. Here, we sought to (a) quantify natural gas residual fluid sources and endpoints to bound the scope of potential waste stream impacts and (b) describe the organic pollutants discharged to surface waters following treatment, a route of likely ecological exposure. Our findings indicate that centralized waste treatment facilities (CWTF) received 9.5% (8.5 * 10(8) L) of natural gas residual fluids in 2013, with some facilities discharging all effluent to surface waters. In dry months, discharged water volumes were on the order of the receiving body flows for some plants, indicating that surface waters can become waste-dominated in summer. As disclosed organic compounds used in high volume hydraulic fracturing (HVHF) vary greatly in physicochemical properties, we deployed a suite of analytical techniques to characterize CWTF effluents, covering 90.5% of disclosed compounds. Results revealed that, of nearly 1000 disclosed organic compounds used in HVHF, only petroleum distillates and alcohol polyethoxylates were present. Few analytes targeted by regulatory agencies (e.g., benzene or toluene) were observed, highlighting the need for expanded and improved monitoring efforts at CWTFs. PMID- 26147420 TI - Anatomical insights into sacrocolpopexy for multicompartment pelvic organ prolapse. AB - AIMS: Pelvic organ prolapse occurs in 50% of parous women. Laparoscopic sacrocolpopexy (LSCP) is a common surgical procedure for restoring pelvic anatomy and function. The aim of this study is to evaluate surgical anatomy and anatomical modifications induced by standardized LSCP. METHODS: Ten fresh female cadavers underwent LSCP, six subsequently underwent standard anatomical dissection, and four had sagittal anatomical dissection. Four cadavers were used as control subjects; two of them underwent standard anatomical dissection, and two had sagittal anatomical dissection. RESULTS: Vesicovaginal space dissection resulted in an arrow-shaped space limited by the trigone and vesical branches of the uterine artery. Rectovaginal space dissection resulted in an inverted V shaped space marked by the utero-sacral and rectovaginal ligaments, the cranial end of the perineal body and the levator ani muscle. Exposing the longitudinal vertebral ligament through a peritoneal and presacral fascia incision along the medial border of the right common iliac artery allowed the identification and the preservation of the right hypogastric nerve. The anterior mesh stretched across the proximal half of the anterior vaginal wall, and the cervix towards the sacral promontory provided excellent cervix suspension and anterior-vaginal wall support with a concomitant stretch of the pubocervical fascia. The median angle formed by the axis of the infra-levatorial vagina with the axis of the supra-levatorial vagina changed from 142 degrees to 171 degrees and determined the linearization ventralization of the vaginal canal. CONCLUSIONS: LSCP can be performed in a nerve-sparing, standardized fashion, providing excellent apical suspension and anterior vaginal wall support. Neurourol. Urodynam. 35:813-818, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26147421 TI - Homogeneous Nature of Malaysian Marine Fish Epinephelus fuscoguttatus (Perciformes; Serranidae): Evidence Based on Molecular Markers, Morphology and Fourier Transform Infrared Analysis. AB - Taxonomic confusion exists within the genus Epinephelus due to the lack of morphological specializations and the overwhelming number of species reported in several studies. The homogenous nature of the morphology has created confusion in the Malaysian Marine fish species Epinephelus fuscoguttatus and Epinephelus hexagonatus. In this study, the partial DNA sequence of the 16S gene and mitochondrial nucleotide sequences of two gene regions, Cytochrome Oxidase Subunit I and III were used to investigate the phylogenetic relationship between them. In the phylogenetic trees, E. fuscoguttatus was monophyletic with E. hexagonatus species and morphology examination shows that no significant differences were found in the morphometric features between these two taxa. This suggests that E. fuscoguttatus is not distinguishable from E. hexagonatus species, and that E. fuscoguttatus have been identified to be E. hexagonatus species is likely attributed to differences in environment and ability to camouflage themselves under certain conditions. Interestingly, this finding was also supported by Principal Component Analysis on Attenuated Total Reflectance Fourier-transform Infrared (ATR-FTIR) data analysis. Molecular, morphological and meristic characteristics were combined with ATR-FTIR analysis used in this study offer new perspectives in fish species identification. To our knowledge, this is the first report of an extensive genetic population study of E. fuscoguttatus in Malaysia and this understanding will play an important role in informing genetic stock-specific strategies for the management and conservation of this highly valued fish. PMID- 26147422 TI - Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity. AB - Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF 36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients. PMID- 26147423 TI - Synthesis of Unsaturated Polyester Resins from Various Bio-Derived Platform Molecules. AB - Utilisation of bio-derived platform molecules in polymer synthesis has advantages which are, broadly, twofold; to digress from crude oil dependence of the polymer industry and secondly to reduce the environmental impact of the polymer synthesis through the inherent functionality of the bio-derived platform molecules. Bulk polymerisation of bio-derived unsaturated di-acids has been employed to produce unsaturated polyester (UPEs) which have been analysed by GPC, TGA, DSC and NMR spectroscopy, advancing on the analysis previously reported. UPEs from the diesters of itaconic, succinic, and fumaric acids were successfully synthesised with various diols and polyols to afford resins of MN 480-477,000 and Tg of -30.1 to -16.6 degrees C with solubilities differing based on starting monomers. This range of properties allows for many applications and importantly due to the surviving Michael acceptor moieties, solubility and cross-linking can be specifically tailored, post polymerisation, to the desired function. An improved synthesis of itaconate and succinate co-polymers, via the initial formation of an itaconate bis-diol, is also demonstrated for the first time, resulting in significantly improved itaconate incorporation. PMID- 26147424 TI - Terminal Mannose Residues in Seminal Plasma Glycoproteins of Infertile Men Compared to Fertile Donors. AB - The impact of seminal plasma components on the fertilization outcomes in humans is still under question. The increasing number of couples facing problems with conception raises the need for predictive biomarkers. Detailed understanding of the molecular mechanisms accompanying fertilization remains another challenge. Carbohydrate-protein recognition may be of key importance in this complex field. In this study, we analyzed the unique glycosylation pattern of seminal plasma proteins, the display of high-mannose and hybrid-type oligosaccharides, by means of their reactivity with mannose-specific Galanthus nivalis lectin. Normozoospermic infertile subjects presented decreased amounts of lectin-reactive glycoepitopes compared to fertile donors and infertile patients with abnormal semen parameters. Glycoproteins containing unveiled mannose were isolated in affinity chromatography, and 17 glycoproteins were identified in liquid chromatography-tandem mass spectrometry with electrospray ionization. The N glycome of the isolated glycoproteins was examined in matrix-assisted laser desorption ionization mass spectrometry. Eleven out of 27 identified oligosaccharides expressed terminal mannose residues, responsible for lectin binding. We suggest that lowered content of high-mannose and hybrid type glycans in normozoospermic infertile patients may be associated with impaired sperm protection from preterm capacitation and should be considered in the search for new infertility markers. PMID- 26147425 TI - Cutaneous Adverse Events Associated with Interferon-beta Treatment of Multiple Sclerosis. AB - Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-beta who developed new onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs. PMID- 26147426 TI - Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis. AB - Osteoarthritis (OA) is a chronic, progressive, and irreversible degenerative joint disease. Conventional OA treatments often result in complications such as pain and limited activity. However, transplantation of mesenchymal stem cells (MSCs) has several beneficial effects such as paracrine effects, anti inflammatory activity, and immunomodulatory capacity. In addition, MSCs can be differentiated into several cell types, including chondrocytes, osteocytes, endothelia, and adipocytes. Thus, transplantation of MSCs is a suggested therapeutic tool for treatment of OA. However, transplanted naive MSCs can cause problems such as heterogeneous populations including differentiated MSCs and undifferentiated cells. To overcome this problem, new strategies for inducing differentiation of MSCs are needed. One possibility is the application of microRNA (miRNA) and small molecules, which regulate multiple molecular pathways and cellular processes such as differentiation. Here, we provide insight into possible strategies for cartilage regeneration by transplantation of differentiated MSCs to treat OA patients. PMID- 26147427 TI - 8-p-Hdroxybenzoyl Tovarol Induces Paraptosis Like Cell Death and Protective Autophagy in Human Cervical Cancer HeLa Cells. AB - 8-p-Hdroxybenzoyl tovarol (TAW) is a germacrane-type sesquiterpenoid that can be isolated from the roots of Ferula dissecta (Ledeb.) Ledeb. In this study, the growth inhibitory effects induced by TAW were screened on some types of tumor cells, and the mechanism was investigated on TAW-induced growth inhibition, including paraptosis and autophagy in human cervical cancer HeLa cells. TAW induced paraptosis involved extensive cytoplasmic vacuolization in the absence of caspase activation. Additionally, TAW evoked cell paraptotic death mediated by endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Autophagy induced by TAW was found to antagonize paraptosis in HeLa cells. This effect was enhanced by rapamycin and suppressed by the autophagy inhibitor, 3-methyladenine (3MA). Loss of beclin 1 (an autophagic regulator) function led to promote ER stress. Taken together, these results suggest that TAW induces paraptosis like cell death and protective autophagy in HeLa cells, which would provide a new clue for exploiting TAW as a promising agent for the treatment of cervical cancer. PMID- 26147428 TI - Expression of Human DNAJ (Heat Shock Protein-40) B3 in Humanized UDP glucuronosyltransferase 1 Mice. AB - The human DNAJB3 gene encodes a DNAJ (Heat shock protein 40; Hsp40) homolog, subfamily B, member 3 chaperone protein (DNAJB3), which can be down-regulated in disease conditions, as observed in decreased expression of DNAJB3 mRNA in peripheral blood mononuclear cells (PBMC) of obese patients. Recently, humanized UDP-glucuronosyltransferase (UGT) 1 mice (hUGT1 mice) were developed, in which the introduced human UGT1 gene contained a gene encoding human DNAJB3. In the present study, we analyzed the expression of human DNAJB3 mRNA in hUGT1 mice. Among the examined tissues, the testis had the highest expression of human DNAJB3 mRNA, while the lowest expression was observed in the liver. We found that the pattern of tissue-specific expression of mouse Dnajb3 in hUGT1 mice was very similar to that of human DNAJB3. We further demonstrated that the expression of human DNAJB3 in the liver was significantly reduced in high-fat-diet-fed hUGT1 mice compared to the expression level in the control mice, indicating that the expression of human DNAJB3 in hUGT1 mice could be similarly regulated in disease conditions such as obesity. Humanized UGT1 mice might therefore be useful to investigate the physiological role of human DNAJB3 in vivo. PMID- 26147429 TI - Identification and Characterization of 40 Isolated Rehmannia glutinosa MYB Family Genes and Their Expression Profiles in Response to Shading and Continuous Cropping. AB - The v-myb avian myeloblastosis viral oncogene homolog (MYB) superfamily constitutes one of the most abundant groups of transcription factors (TFs) described in plants. To date, little is known about the MYB genes in Rehmannia glutinosa. Forty unique MYB genes with full-length cDNA sequences were isolated. These 40 genes were grouped into five categories, one R1R2R3-MYB, four TRFL MYBs, four SMH MYBs, 25 R2R3-MYBs, and six MYB-related members. The MYB DNA-binding domain (DBD) sequence composition was conserved among proteins of the same subgroup. As expected, most of the closely related members in the phylogenetic tree exhibited common motifs. Additionally, the gene structure and motifs of the R. glutinosa MYB genes were analyzed. MYB gene expression was analyzed in the leaf and the tuberous root under two abiotic stress conditions. Expression profiles showed that most R. glutinosa MYB genes were expressed in the leaf and the tuberous root, suggesting that MYB genes are involved in various physiological and developmental processes in R. glutinosa. Seven MYB genes were up-regulated in response to shading in at least one tissue. Two MYB genes showed increased expression and 13 MYB genes showed decreased expression in the tuberous root under continuous cropping. This investigation is the first comprehensive study of the MYB gene family in R. glutinosa. PMID- 26147430 TI - Assessement of the pharmacokinetics, tissue distribution and excretion studies of a novel antiplatelet agent S007-867, following administration to rats. AB - S007-867 is a promising novel antiplatelet agent with better efficacy and lesser bleeding risk than existing agents. The present study investigated the absorption, tissue distribution, and excretion of S007-867 in rat model for further advancement of the molecule. A simple and robust ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) bioanalytical method was used to determine S007-867 in various matrices. Following oral administration, the compound was quickly dispersed in the various tissues and peak concentration levels were achieved within 0.5-1 h. Overall, exposure of drug, i.e., AUC in different tissues was found in the order of small intestine > liver > heart > spleen > lungs > kidney > brain. The total recoveries of the S007-867 within 96 h were 3.36% in urine and faeces. This might be due to a first-pass effect by the liver and intestine as most of the drug was eliminated in metabolite form. These findings provide a crucial information about further development of S007-867 as antithrombotic agent. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26147431 TI - Intracranial recordings reveal transient response dynamics during information maintenance in human cerebral cortex. AB - Despite an extensive body of work, it is still not clear how short term maintenance of information is implemented in the human brain. Most prior research has focused on "working memory"-typically involving the storage of a number of items, requiring the use of a phonological loop and focused attention during the delay period between encoding and retrieval. These studies largely support a model of enhanced activity in the delay interval as the central mechanism underlying working memory. However, multi-item working memory constitutes only a subset of storage phenomena that may occur during daily life. A common task in naturalistic situations is short term memory of a single item-for example, blindly reaching to a previously placed cup of coffee. Little is known about such single-item, effortless, storage in the human brain. Here, we examined the dynamics of brain responses during a single-item maintenance task, using intracranial recordings implanted for clinical purpose in patients (ECoG). Our results reveal that active electrodes were dominated by transient short latency visual and motor responses, reflected in broadband high frequency power increases in occipito-temporal, frontal, and parietal cortex. Only a very small set of electrodes showed activity during the early part of the delay period. Interestingly, no cortical site displayed a significant activation lasting to the response time. These results suggest that single item encoding is characterized by transient high frequency ECoG responses, while the maintenance of information during the delay period may be mediated by mechanisms necessitating only low levels of neuronal activations. PMID- 26147432 TI - A Proposed Atomic Structure of the Self-Assembly of the Non-Amyloid-beta Component of Human alpha-Synuclein As Derived by Computational Tools. AB - alpha-Synuclein (AS) fibrils are the major hallmarks of Parkinson's disease (PD). It is known that the central domain of the 140-residue AS protein, known as the non-amyloid-beta component (NAC), plays a crucial role in aggregation. The secondary structure of AS fibrils (including the NAC domain) has been proposed on the basis of solid-state nuclear magnetic resonance studies, but the atomic structure of the self-assembly of NAC (or AS itself) is still elusive. This is the first study that presents a detailed three-dimensional structure of NAC at atomic resolution. The proposed self-assembled structure of NAC consists of three beta-strands connected by two turn regions. Our study shows that calculated structural parameter values of the simulated fibril-like cross-beta structure of NAC are in excellent agreement with the experimental values. Moreover, the diameter dimensions of the proposed fibril-like structure are also in agreement with experimental measurements. The proposed fibril-like structure of NAC may assist in future work aimed at understanding the formation of aggregates in PD and developing compounds to modulate aggregation. PMID- 26147433 TI - Metallome of Pseudomonas aeruginosa: a role for siderophores. AB - In this paper, we describe the total metal composition (metallome) of Pseudomonas aeruginosa. Inductively coupled plasma atomic emission spectroscopy analyses showed that P. aeruginosa cells concentrate each metal of the metallome from the extracellular media with different efficiencies. Growth in nutrient-restricted media did not substantially affect the overall profile of the metallome; however, the uptake of some metals was strongly stimulated, showing the high potential of some metal acquisition pathways to adapt to changing growth conditions. We also investigated the role of the two major siderophores produced by P. aeruginosa, pyoverdine and pyochelin, in iron uptake and more generally in metallome homeostasis. In addition to their role in iron acquisition, siderophore production also significantly prevented the accumulation of toxic metals in P. aeruginosa cells, thus preserving the equilibrium of the metallome in a polluted environment. PMID- 26147434 TI - Inhibition of Thrombopoietin/Mpl Signaling in Adult Hematopoiesis Identifies New Candidates for Hematopoietic Stem Cell Maintenance. AB - Thrombopoietin (Thpo) signals via its receptor Mpl and regulates megakaryopoiesis, hematopoietic stem cell (HSC) maintenance and post-transplant expansion. Mpl expression is tightly controlled and deregulation of Thpo/Mpl signaling is linked to hematological disorders. Here, we constructed an intracellular-truncated, signaling-deficient Mpl protein which is presented on the cell surface (dnMpl). The transplantation of bone marrow cells retrovirally transduced to express dnMpl into wildtype mice induced thrombocytopenia, and a progressive loss of HSC. The aplastic BM allowed the engraftment of a second BM transplant without further conditioning. Functional analysis of the truncated Mpl in vitro and in vivo demonstrated no internalization after Thpo binding and the inhibition of Thpo/Mpl-signaling in wildtype cells due to dominant-negative (dn) effects by receptor competition with wildtype Mpl for Thpo binding. Intracellular inhibition of Mpl could be excluded as the major mechanism by the use of a constitutive-dimerized dnMpl. To further elucidate the molecular changes induced by Thpo/Mpl-inhibition on the HSC-enriched cell population in the BM, we performed gene expression analysis of Lin-Sca1+cKit+ (LSK) cells isolated from mice transplanted with dnMpl transduced BM cells. The gene expression profile supported the exhaustion of HSC due to increased cell cycle progression and identified new and known downstream effectors of Thpo/Mpl-signaling in HSC (namely TIE2, ESAM1 and EPCR detected on the HSC-enriched LSK cell population). We further compared gene expression profiles in LSK cells of dnMpl mice with human CD34+ cells of aplastic anemia patients and identified similar deregulations of important stemness genes in both cell populations. In summary, we established a novel way of Thpo/Mpl inhibition in the adult mouse and performed in depth analysis of the phenotype including gene expression profiling. PMID- 26147435 TI - The Crystal Structure of Thermotoga maritima Class III Ribonucleotide Reductase Lacks a Radical Cysteine Pre-Positioned in the Active Site. AB - Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides, the building blocks for DNA synthesis, and are found in all but a few organisms. RNRs use radical chemistry to catalyze the reduction reaction. Despite RNR having evolved several mechanisms for generation of different kinds of essential radicals across a large evolutionary time frame, this initial radical is normally always channelled to a strictly conserved cysteine residue directly adjacent to the substrate for initiation of substrate reduction, and this cysteine has been found in the structures of all RNRs solved to date. We present the crystal structure of an anaerobic RNR from the extreme thermophile Thermotoga maritima (tmNrdD), alone and in several complexes, including with the allosteric effector dATP and its cognate substrate CTP. In the crystal structure of the enzyme as purified, tmNrdD lacks a cysteine for radical transfer to the substrate pre-positioned in the active site. Nevertheless activity assays using anaerobic cell extracts from T. maritima demonstrate that the class III RNR is enzymatically active. Other genetic and microbiological evidence is summarized indicating that the enzyme is important for T. maritima. Mutation of either of two cysteine residues in a disordered loop far from the active site results in inactive enzyme. We discuss the possible mechanisms for radical initiation of substrate reduction given the collected evidence from the crystal structure, our activity assays and other published work. Taken together, the results suggest either that initiation of substrate reduction may involve unprecedented conformational changes in the enzyme to bring one of these cysteine residues to the expected position, or that alternative routes for initiation of the RNR reduction reaction may exist. Finally, we present a phylogenetic analysis showing that the structure of tmNrdD is representative of a new RNR subclass IIIh, present in all Thermotoga species plus a wider group of bacteria from the distantly related phyla Firmicutes, Bacteroidetes and Proteobacteria. PMID- 26147436 TI - Molecular Effects of Polymorphism in the 3'UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins. AB - Conception rates among dairy cows in Japan have declined in recent decades. To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3' untranslated region (UTR) of unc-5 homolog C (UNC5C). Cows with higher conception rates carried the A polymorphism in the UNC5C 3'UTR. Luciferase assays and quantitative analysis of allele ratios revealed that UNC5C transcripts with the A polymorphism were expressed at higher levels than those carrying the G polymorphism. UNC5C transmits either pro- or anti-apoptotic signals depending on the availability of its ligand, Netrin-1. UNC5C expression is negatively regulated by reproductive homeobox X-linked 5 (Rhox5), and the Rhox5 locus is methylated by G9a methyltransferase. G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased. Repression of UNC5C, G9a, or Netrin-1 or forced expression of Rhox5 in the anterior nucleus stage inhibited development to the blastocyst stage, suggesting that cows carrying the G polymorphism in UNC5C might have lower conception rates because of the poor development of preimplantation embryos. This study provides novel insights into the role of UNC5C during embryonic development. PMID- 26147438 TI - Optimising Regionalisation Techniques: Identifying Centres of Endemism in the Extraordinarily Endemic-Rich Cape Floristic Region. AB - We used a very large dataset (>40% of all species) from the endemic-rich Cape Floristic Region (CFR) to explore the impact of different weighting techniques, coefficients to calculate similarity among the cells, and clustering approaches on biogeographical regionalisation. The results were used to revise the biogeographical subdivision of the CFR. We show that weighted data (down weighting widespread species), similarity calculated using Kulczinsky's second measure, and clustering using UPGMA resulted in the optimal classification. This maximized the number of endemic species, the number of centres recognized, and operational geographic units assigned to centres of endemism (CoEs). We developed a dendrogram branch order cut-off (BOC) method to locate the optimal cut-off points on the dendrogram to define candidate clusters. Kulczinsky's second measure dendrograms were combined using consensus, identifying areas of conflict which could be due to biotic element overlap or transitional areas. Post clustering GIS manipulation substantially enhanced the endemic composition and geographic size of candidate CoEs. Although there was broad spatial congruence with previous phytogeographic studies, our techniques allowed for the recovery of additional phytogeographic detail not previously described for the CFR. PMID- 26147437 TI - Inter-Ethnic Differences in Quantified Coronary Artery Disease Severity and All Cause Mortality among Dutch and Singaporean Percutaneous Coronary Intervention Patients. AB - BACKGROUND: Coronary artery disease (CAD) is a global problem with increasing incidence in Asia. Prior studies reported inter-ethnic differences in the prevalence of CAD rather than the severity of CAD. The angiographic "synergy between percutaneous coronary intervention (PCI) with taxus and cardiac surgery" (SYNTAX) score quantifies CAD severity and predicts outcomes. We studied CAD severity and all-cause mortality in four globally populous ethnic groups: Caucasians, Chinese, Indians and Malays. METHODS: We quantified SYNTAX scores of 1,000 multi-ethnic patients undergoing PCI in two tertiary hospitals in the Netherlands (Caucasians) and Singapore (Chinese, Indians and Malays). Within each ethnicity we studied 150 patients with stable CAD and 100 with ST-elevated myocardial infarction (STEMI). We made inter-ethnic comparisons of SYNTAX scores and all-cause mortality. RESULTS: Despite having a younger age (mean age Indians: 56.8 and Malays: 57.7 vs. Caucasians: 63.7 years), multivariable adjusted SYNTAX scores were significantly higher in Indians and Malays than Caucasians with stable CAD: 13.4 [11.9-14.9] and 13.4 [12.0-14.8] vs. 9.4 [8.1-10.8], p<0.001. Among STEMI patients, SYNTAX scores were highest in Chinese and Malays: 17.7 [15.9-19.5] and 18.8 [17.1-20.6] vs. 15.5 [13.5-17.4] and 12.7 [10.9-14.6] in Indians and Caucasians, p<0.001. Over a median follow-up of 709 days, 67 deaths (stable CAD: 37, STEMI: 30) occurred. Among STEMI patients, the SYNTAX score independently predicted all-cause mortality: HR 2.5 [1.7-3.8], p<0.001 for every 10-point increase. All-cause mortality was higher in Indian and Malay STEMI patients than Caucasians, independent of SYNTAX score (adjusted HR 7.2 [1.5 34.7], p=0.01 and 5.8 [1.2-27.2], p=0.02). CONCLUSION: Among stable CAD and STEMI patients requiring PCI, CAD is more severe in Indians and Malays than in Caucasians, despite having a younger age. Moreover, Indian and Malay STEMI patients had a greater adjusted risk of all-cause mortality than Caucasians, independent of SYNTAX score. PMID- 26147439 TI - Inhibition of Calcium Influx Reduces Dysfunction and Apoptosis in Lipotoxic Pancreatic beta-Cells via Regulation of Endoplasmic Reticulum Stress. AB - Lipotoxicity plays an important role in pancreatic beta-cell failure during the development of type 2 diabetes. Prolonged exposure of beta-cells to elevated free fatty acids level could cause deterioration of beta-cell function and induce cell apoptosis. Therefore, inhibition of fatty acids-induced beta-cell dysfunction and apoptosis might provide benefit for the therapy of type 2 diabetes. The present study examined whether regulation of fatty acids-triggered calcium influx could protect pancreatic beta-cells from lipotoxicity. Two small molecule compounds, L type calcium channel blocker nifedipine and potassium channel activator diazoxide were used to inhibit palmitic acid-induced calcium influx. And whether the compounds could reduce palmitic acid-induced beta-cell failure and the underlying mechanism were also investigated. It was found that both nifedipine and diazoxide protected MIN6 pancreatic beta-cells and primary cultured murine islets from palmitic acid-induced apoptosis. Meanwhile, the impaired insulin secretion was also recovered to varying degrees by these two compounds. Our results verified that nifedipine and diazoxide could reduce palmitic acid-induced endoplasmic reticulum stress to generate protective effects on pancreatic beta-cells. More importantly, it suggested that regulation of calcium influx by small molecule compounds might provide benefits for the prevention and therapy of type 2 diabetes. PMID- 26147440 TI - Manganese is an additional cation that enhances colonial phase variation of Vibrio vulnificus. AB - Vibrio vulnificus, an inhabitant of marine and estuarine environments around the world, is the leading cause of reported seafood-related deaths in the United States. Disease is caused by opaque colony-forming strains that produce capsular polysaccharide, loss of which results in an unencapsulated translucent phenotype with diminished virulence potential. Rugose is a third phenotypic variant of V. vulnificus, and produces a separate exopolysaccharide that results in a dry, wrinkled appearance and the ability to form profuse biofilms. Phase variation among these three phenotypes is influenced by several environmental factors, including the presence of calcium in the medium (Garrison-Schilling et al.). In this study, we have identified a second cation, manganese, which substantially increases the propensity of opaque V. vulnificus strains to switch to translucent or rugose phenotypes. In comparative studies, manganese and calcium promoted switching to the same phenotype for some strains but to different phenotypes for others, results of which indicate that the two cations do not always promote the same changes in underlying gene expression. The data here provide further evidence that exposure of V. vulnificus to select cations results in phenotypic changes that impact both virulence capacity and ecology of the organism. PMID- 26147442 TI - Comparison of linear energy transfer scoring techniques in Monte Carlo simulations of proton beams. AB - Monte Carlo (MC) simulations are commonly used to study linear energy transfer (LET) distributions in therapeutic proton beams. Various techniques have been used to score LET in MC simulations. The goal of this work was to compare LET distributions obtained using different LET scoring techniques and examine the sensitivity of these distributions to changes in commonly adjusted simulation parameters. We used three different techniques to score average proton LET in TOPAS, which is a MC platform based on the Geant4 simulation toolkit. We determined the sensitivity of each scoring technique to variations in the range production thresholds for secondary electrons and protons. We also compared the depth-LET distributions that we acquired using each technique in a simple monoenergetic proton beam and in a more clinically relevant modulated proton therapy beam. Distributions of both fluence-averaged LET (LETPhi) and dose averaged LET (LETD) were studied. We found that LETD values varied more between different scoring techniques than the LETPhi values did, and different LET scoring techniques showed different sensitivities to changes in simulation parameters. PMID- 26147441 TI - C6 Peptide-Based Multiplex Phosphorescence Analysis (PHOSPHAN) for Serologic Confirmation of Lyme Borreliosis. AB - BACKGROUND: A single-tier immunoassay using the C6 peptide of VlsE (C6) from Borrelia burgdorferi sensu stricto (Bb) has been proposed as a potential alternative to conventional two-tier testing for the serologic diagnosis of Lyme disease in the United States and Europe. OBJECTIVE: To evaluate the performance of C6 peptide based multiplex Phosphorescence Analysis (PHOSPHAN) for the serologic confirmation of Lyme borreliosis (LB) in Russian patients. METHODS: Serum samples (n = 351) were collected from 146 patients with erythema migrans (EM); samples from 131 of these patients were taken several times prior to treatment and at different stages of recovery. The control group consisted of 197 healthy blood donors and 31 patients with other diseases, all from the same highly endemic region of Russia. All samples were analyzed by PHOSPHAN for IgM and IgG to Bb C6, recombinant OspC and VlsE proteins, and C6 peptides from B. garinii and B. afzelii. RESULTS: IgM and IgG to Bb C6 were identified in 43 and 95 out of 131 patients (32.8 and 72.5%, respectively); seroconversion of IgM antibodies was observed in about half of the patients (51.2%), and of IgG antibodies, in almost all of them (88.4%). Additional detection of OspC-IgM and VlsE-IgM or IgG to C6 from B. garinii or B. afzelii did not contribute significantly to the overall sensitivity of the multiplex immunoassay. CONCLUSIONS: The multiplex phosphorescence immunoassay is a promising method for simultaneously revealing the spectrum of antibodies to several Borrelia antigens. Detection of IgM and IgG to Bb C6 in the sera of EM patients provides effective serologic confirmation of LB and, with high probability, indicates an active infection process. PMID- 26147443 TI - A Review: Supplementation of Foods with Essential Fatty Acids-Can It Turn a Breeze without Further Ado? AB - This paper focuses on the critical aspects of supplementation of foods with essential fatty acids (EFAs), the need, health benefits of supplementation and the constraints of the process. Current trend of supplementation of foods with EFAs has been gaining momentum and more research pioneers due to the health benefits in par with the direct intake of EFA supplements. Technologies including encapsulation, nanotechnology, molecular complexing, genetic engineering and more emerging means, hold promise to food supplementation with EFAs. Food trials with adoption of various technologies, studies of bioavailability and health benefits are still underway and crucial before EFA supplementation in foods can hit the market on a global scale. PMID- 26147445 TI - Poles Apart: Comparing Trends of Alien Hymenoptera in New Zealand with Europe (DAISIE). AB - Developing generalisations of invasive species is an important part of invasion biology. However, trends and generalisations from one part of the world may not necessarily hold elsewhere. We present the first inventory and analysis of all Hymenoptera alien to New Zealand, and compare patterns from New Zealand with those previously published from Europe (DAISIE). Between the two regions there was broad correlation between families with the highest number of alien species (Braconidae, Encyrtidae, Pteromalidae, Eulophidae, Formicidae, Aphelinidae). However, major differences also existed. The number of species alien to New Zealand is higher than for Europe (334 vs 286), and major differences include: i) the much lower proportion of intentionally released species in New Zealand (21% vs 63% in Europe); and ii) the greater proportion of unintentionally introduced parasitoids in New Zealand (71.2% vs 22.6%). The disharmonic 'island' nature of New Zealand is shown, as a high proportion of families (36%) have no native representatives, and alien species also represent >10% of the native fauna for many other families. A much larger proportion of alien species are found in urban areas in New Zealand (60%) compared to Europe (~30%), and higher numbers of alien species were present earlier in New Zealand (especially <1950). Differences in the origins of alien species were also apparent. Unlike Europe, the New Zealand data reveals a change in the origins of alien species over time, with an increasing dominance of alien species from Australasia (a regional neighbour) during the past 25 years. We recommend that further effort be made towards the formation, and analysis, of regional inventories of alien species. This will allow a wider range of taxa and regions to be examined for generalisations, and help assess and prioritise the risk posed by certain taxa towards the economy or environment. PMID- 26147444 TI - A three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes. AB - Assembly of a bipolar microtubule spindle is essential for accurate chromosome segregation. In somatic cells, spindle bipolarity is determined by the presence of exactly two centrosomes. Remarkably, mammalian oocytes do not contain canonical centrosomes. This study reveals that mouse oocytes assemble a bipolar spindle by fragmenting multiple acentriolar microtubule-organizing centres (MTOCs) into a high number of small MTOCs to be able to then regroup and merge them into two equal spindle poles. We show that MTOCs are fragmented in a three step process. First, PLK1 triggers a decondensation of the MTOC structure. Second, BicD2-anchored dynein stretches the MTOCs into fragmented ribbons along the nuclear envelope. Third, KIF11 further fragments the MTOCs following nuclear envelope breakdown so that they can be evenly distributed towards the two spindle poles. Failure to fragment MTOCs leads to defects in spindle assembly, which delay chromosome individualization and congression, putting the oocyte at risk of aneuploidy. PMID- 26147446 TI - Sustained complete remission of advanced hepatocellular carcinoma with sorafenib therapy. PMID- 26147447 TI - Violence associated with combat-related posttraumatic stress disorder: The importance of anger. AB - The importance of anger with regard to violence among veterans with combat related PTSD has received little attention. We previously proposed that in PTSD the activation of threat-related cognitive networks strongly potentiates anger in a positive feedback loop and that inhibitory controls on aggression can be overridden when PTSD and anger activation are conjoined. We predicted that violence would be intensified when combat-related PTSD was conjoined with anger. We used the National Vietnam Veterans Readjustment Study (NVVRS) public use data set, selecting the male combat theater veterans, which entailed 1,200 from the main survey (Study 1) and 259 from the clinical interview component (Study 2). Anger indices were constructed from NVVRS variables. PTSD was assessed by continuous symptom scores and by clinical diagnostic measures. Conjoined anger and PTSD was associated with greatly increased violence. PTSD was not associated with violence in the absence of anger. This result was obtained using alternative measures of PTSD and of anger in both the main survey and the clinical interview component. These findings call for reconceptualizing the association of PTSD and violence. Concerted attention should be given to anger as a risk factor for violence in the assessment and treatment of combat-related PTSD, and as an important portal of entry for treatment. PMID- 26147448 TI - Hispanic ethnicity and Caucasian race: Relations with posttraumatic stress disorder's factor structure in clinic-referred youth. AB - The severity of posttraumatic stress disorder (PTSD) symptoms is linked to race and ethnicity, albeit with contradictory findings (reviewed in Alcantara, Casement, & Lewis-Fernandez, 2013; Pole, Gone, & Kulkarni, 2008). We systematically examined Caucasian (n = 3,767) versus non-Caucasian race (n = 2,824) and Hispanic (n = 2,395) versus non-Hispanic ethnicity (n = 3,853) as candidate moderators of PTSD's 5-factor model structural parameters (Elhai et al., 2013). The sample was drawn from the National Child Traumatic Stress Network's Core Data Set, currently the largest national data set of clinic referred children and adolescents exposed to potentially traumatic events. Using confirmatory factor analysis, we tested the invariance of PTSD symptom structural parameters by race and ethnicity. Chi-square difference tests and goodness-of-fit values showed statistical equivalence across racial and ethnic groups in the factor structure of PTSD and in mean item-level indicators of PTSD symptom severity. Results support the structural invariance of PTSD's 5-factor model across the compared racial and ethnic groups. Furthermore, results indicated equivalent item-level severity across racial and ethnic groups; this supports the use of item-level comparisons across these groups. PMID- 26147449 TI - Transcriptome and Molecular Pathway Analysis of the Hepatopancreas in the Pacific White Shrimp Litopenaeus vannamei under Chronic Low-Salinity Stress. AB - The Pacific white shrimp Litopenaeus vannamei is a euryhaline penaeid species that shows ontogenetic adaptations to salinity, with its larvae inhabiting oceanic environments and postlarvae and juveniles inhabiting estuaries and lagoons. Ontogenetic adaptations to salinity manifest in L. vannamei through strong hyper-osmoregulatory and hypo-osmoregulatory patterns and an ability to tolerate extremely low salinity levels. To understand this adaptive mechanism to salinity stress, RNA-seq was used to compare the transcriptomic response of L. vannamei to changes in salinity from 30 (control) to 3 practical salinity units (psu) for 8 weeks. In total, 26,034 genes were obtained from the hepatopancreas tissue of L. vannamei using the Illumina HiSeq 2000 system, and 855 genes showed significant changes in expression under salinity stress. Eighteen top Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly involved in physiological responses, particularly in lipid metabolism, including fatty-acid biosynthesis, arachidonic acid metabolism and glycosphingolipid and glycosaminoglycan metabolism. Lipids or fatty acids can reduce osmotic stress in L. vannamei by providing additional energy or changing the membrane structure to allow osmoregulation in relevant organs, such as the gills. Steroid hormone biosynthesis and the phosphonate and phosphinate metabolism pathways were also involved in the adaptation of L. vannamei to low salinity, and the differential expression patterns of 20 randomly selected genes were validated by quantitative real-time PCR (qPCR). This study is the first report on the long-term adaptive transcriptomic response of L. vannamei to low salinity, and the results will further our understanding of the mechanisms underlying osmoregulation in euryhaline crustaceans. PMID- 26147450 TI - Dietary Antioxidants and Melanoma: Evidence from Cohort and Intervention Studies. AB - Melanoma is the most serious form of skin cancer affecting mostly people of Caucasian origin and is associated with high exposure to solar ultraviolet (UV) radiation. Antioxidants in the diet are thought to prevent UV-induced DNA damage and oxidative stress and laboratory-based studies have shown that high antioxidant intakes inhibit melanoma development. Corresponding epidemiological evidence is inconsistent, however. We therefore reviewed results from prospective observational studies and randomized controlled trials (RCTs) to clarify whether consumption of antioxidant vitamin C, E (tocopherol), and A (retinol), carotenoids and selenium, as food, supplements, or both, or high fruit and vegetable intake, reduce the incidence of cutaneous melanoma. A total of 9 studies (2 cohort, 1 nested case-control, 6 RCTs) were included. Neither antioxidant nutrients, individually or combined, nor fruit and vegetable intake showed any strong and significant associations with melanoma, though the number of relevant studies was limited and several had methodological shortcomings. In particular, melanoma was not a primary disease outcome in any of the RCTs and therefore, none adequately accounted for potential confounding by sun exposure. In conclusion, available evidence is currently inadequate to assess possible beneficial effects of antioxidant intake on melanoma risk. PMID- 26147451 TI - Displacement or Force Control Knee Simulators? Variations in Kinematics and in Wear. AB - The problems associated with prosthetic failure and revision surgery still constitute the main clinical problem of prosthetic surgery. The objective of wear evaluation is to determine the wear rate and its dependence on the test conditions. To obtain realistic results, a wear test can be performed to reproduce in vivo working conditions and compare the wear characteristics of various total knee prostheses designs. At the state of the art, two simulation concepts are available and defined in ISO 14243 standards series. In both these guidelines, level walking is the sole activity of daily living that is represented for testing. With so many variables and so many sources of error and the sensitivity of the output to these errors, can the motion determined in the simulator be representative of the in vivo motion? This article goes beyond the current status of these knee simulations comparing literature results. PMID- 26147452 TI - Epstein-Barr virus modulates host cell microRNA-194 to promote IL-10 production and B lymphoma cell survival. AB - Epstein-Barr virus (EBV) is a gamma-herpesvirus that is linked to the development of posttransplant lymphoproliferative disorder (PTLD) in solid organ recipients. We previously demonstrated that EBV(+) B cell lymphoma cell lines isolated from patients with PTLD produce human IL-10 as an autocrine growth factor. However, little is known regarding IL-10 regulation in B cells. Here we show that EBV infection markedly alters the expression of host B cell microRNA, a class of small noncoding RNA that is an important regulator of transcriptional and posttranscriptional gene expression. Gene arrays reveal unique microRNA profiles in EBV(+) B cell lymphoma lines from patients with PTLD, compared to normal B cells or in vitro generated EBV(+) lymphoblastoid cell lines. We show that microRNA-194 expression is uniquely suppressed in EBV(+) B cell lines from PTLD patients and that the 3'untranslated region of IL-10 is targeted by microRNA-194. Overexpression of microRNA-194 attenuates IL-10 production and increases apoptosis of EBV(+) B cell lymphoma lines. Together, these data indicate that EBV co-opts the host B cell microRNA network and specifically suppresses microRNA-194 to override control of IL-10 expression. Thus, modulation of microRNA-194 may constitute a novel approach to inhibiting proliferation of EBV(+) B cell lymphomas in PTLD. PMID- 26147453 TI - Sexuality Education Websites for Adolescents: A Framework-Based Content Analysis. AB - The web has unique potential for adolescents seeking comprehensive sexual health information. As such, it is important to understand the nature, scope, and readability of the content and messaging provided by sexuality educational websites. We conducted a content analysis of 14 sexuality education websites for adolescents, based on the 7 essential components (sexual and reproductive health and HIV, relationships, sexual rights and sexual citizenship, pleasure, violence, diversity, and gender) of the International Planned Parenthood Framework for Comprehensive Sexuality Education. A majority of content across all sites focused on sexual and reproductive health and HIV, particularly pregnancy and STI prevention, and other information about STIs and HIV. No other topic comprised more than 10% of content coverage across a majority of sites. The authors found little discussion of gender issues, sexual rights, sexual diversity, or sexual violence. Most sites provided brief references to sexual pleasure, generally moderated with cautionary words. Language used implied a heterosexual female audience. Reading levels for most sites were above the 9th-grade level, with several at the college level. These findings have implications for enhancing online sexuality education and broadening the coverage of essential topics. PMID- 26147454 TI - Thermal response in pre-imaginal biology of Ochlerotatus albifasciatus from two different climatic regions. AB - The biological processes on mosquito could be variable in response to local climatic characteristics. The thermal effects on time and the rate larval development, immature survival and adult size in local populations of Ochlerotatus albifasciatus (Macquart) (Diptera: Culicidae) from cold (Sarmiento) and temperate (Buenos Aires) regions from Argentina were evaluated. This species affects livestock production and human health. Larvae of both regions were placed in breeding thermal baths (11-32 degrees C range). Development and survival were recorded daily until adult emergence. The development temperature threshold and thermal constant for Sarmiento (4.59 +/- 3.08 degrees C, 204.08 +/- 7.83 degree days) was lower and higher than Buenos Aires, respectively (8.06 +/- 1.81 degrees C, 149.25 +/- 2.6 degree days). At cold temperatures (11-16 degrees C), Sarmiento larvae demonstrated 5 days faster development and higher survival (56%) than Buenos Aires (15%), whereas at warm temperatures (20-32 degrees C) were up to 2 days slower and similar survival (16% vs. 18%). The size did not show differences between populations. An Ochlerotatus albifasciatus population seems to present local thermal responses. The favourable temperature for survival and rate of development would vary within a cold or warm range, and these differential responses would explain the wide geographical distribution in different climatic regions of southern South America. PMID- 26147455 TI - Comparison between the efficacy and safety of platelet-rich plasma vs. microdermabrasion in the treatment of striae distensae: clinical and histopathological study. AB - Striae distensae is a challenging cosmetic problem for which various treatment modalities have been applied. To compare between the efficacy and tolerability of intradermal injection of autologous platelet-rich plasma (PRP) vs. microdermabrasion in the treatment of striae distensae. Sixty-eight patients with striae distensae were randomly assigned to three groups according to therapeutic modalities. Patients of group I were treated by intradermal injection of PRP alone, patients of group II were treated with microdermabrasion alone, and patients of group III were treated with combination of intradermal PRP and microdermabrasion in the same session. Each patient underwent maximum of six sessions at 2-week interval. Skin biopsies were taken from some patients at baseline, and 3 months after the last sessions stained with hematoxylin and eosin stain, Masson trichrome, orceun, and Van Gieson stains to study of histopathological changes and efficacy of treatment. There was significant clinical improvement of striae distensae in patients treated with PRP injection and patients treated with combination of PRP and microdermabrasion when compared with patients treated with microdermabrasion. However, combination of PRP and microdermabrasion in the same session showed better results in short duration. Collagen and elastic fibers were markedly increased in the dermis at the end of treatment sessions. Platelet-rich plasma alone is more effective than microdermabrasion alone in the treatment of striae distensae, but it is better to use the combination of both for more and rapid efficacy. However, each one of them is well tolerated by the patients, safe and cost effective. PMID- 26147456 TI - Correlation between shell phenotype and local environment suggests a role for natural selection in the evolution of Placostylus snails. AB - The giant edible Placostylus snails of New Caledonia occur across a wide range of environmental conditions, from the dry southwest to the wetter central and northeastern regions. In large, slow-moving animals such as Placostylus, speciation could be assumed to be largely driven by allopatry and genetic drift as opposed to natural selection. We examined variation in shell morphology using geometric morphometrics and genetic structure within two species of Placostylus (P. fibratus, P. porphyrostomus), to determine the drivers of diversity in this group. Despite the current patchy distribution of snails on New Caledonia, both mtDNA and nuclear SNP data sets (>3000 loci) showed weak admixing between populations and species. Shell morphology was concordant with the genetic clusters we identified and had a strong relationship with local environment. The genetic data, in contrast to the morphological data, did not show concordance with climatic conditions, suggesting the snails are not limited in their ability to adapt to different environments. In sympatry, P. fibratus and P. porphyrostomus maintained genetic and morphological differences, suggesting a genetic basis of phenotypic variation. Convergence of shell shape was observed in two adjacent populations that are genetically isolated but experience similar habitat and climatic conditions. Conversely, some populations in contrasting environments were morphologically distinct although genetically indistinguishable. We infer that morphological divergence in the Placostylus snails of New Caledonia is mediated by adaptation to the local environment. PMID- 26147457 TI - iCOSSY: An Online Tool for Context-Specific Subnetwork Discovery from Gene Expression Data. AB - Pathway analyses help reveal underlying molecular mechanisms of complex biological phenotypes. Biologists tend to perform multiple pathway analyses on the same dataset, as there is no single answer. It is often inefficient for them to implement and/or install all the algorithms by themselves. Online tools can help the community in this regard. Here we present an online gene expression analytical tool called iCOSSY which implements a novel pathway-based COntext specific Subnetwork discoverY (COSSY) algorithm. iCOSSY also includes a few modifications of COSSY to increase its reliability and interpretability. Users can upload their gene expression datasets, and discover important subnetworks of closely interacting molecules to differentiate between two phenotypes (context). They can also interactively visualize the resulting subnetworks. iCOSSY is a web server that finds subnetworks that are differentially expressed in two phenotypes. Users can visualize the subnetworks to understand the biology of the difference. PMID- 26147459 TI - Bone Mineral Measurements. AB - The accurate measurement of bone mineral density using noninvasive methods can be of value in the detection and evaluation of primary and secondary causes of decreased bone mass. This includes primary osteoporosis and secondary disorders, such as hyperparathyroidism, osteomalacia, multiple myeloma, diffuse metastases, and glucocorticoid therapy or intrinsic excess.By far, the largest patient population is that encompassed by primary osteoporosis with increased susceptibility to fractures in the absence of other recognizable causes of bone loss.Primary osteoporosis is a common clinical disorder and a major public health problem because of the significant number of related bone fractures occurring annually. Because the risk of vertebral and femoral neck fractures rises dramatically as bone mineral density falls, fracture risk in individual patients may be estimated. Furthermore, in estrogen-deficient women, bone mineral density values may be used to make rational decisions about hormone replacement therapy, or other bone mineral therapies, and as follow-up in assessing the success of such treatment.In this article, we discuss different methods of bone densitometry and will focus on dual-energy x-ray absorptiometry (DXA) with discussing the factors which should be considered for interpretation of DXA scan. PMID- 26147460 TI - Quality and Safety in Health Care, Part I: Five Pioneers in Quality. AB - Five pioneers had a huge impact on the quality movement in health care in the United States. Ernest Codman contributed in many ways, including his focus on outcome analysis. Avidis Donabedian is known for his focus on the 3 domains of structure, process, and outcome in health care. Walter Shewhart is known especially for the control chart and early work on what W. Edwards Deming made into the PDSA cycle. Deming is also known for other contributions, including his 14 points of management, correcting system problems rather than blaming the workers, and his System of Profound Knowledge. Juran is known for the Pareto principle and his emphasis on customer satisfaction and addressing the human, not just statistical side, of quality improvement. PMID- 26147458 TI - Analysis of the Relationships between DNA Double-Strand Breaks, Synaptonemal Complex and Crossovers Using the Atfas1-4 Mutant. AB - Chromatin Assembly Factor 1 (CAF-1) is a histone chaperone that assembles acetylated histones H3/H4 onto newly synthesized DNA, allowing the de novo assembly of nucleosomes during replication. CAF-1 is an evolutionary conserved heterotrimeric protein complex. In Arabidopsis, the three CAF-1 subunits are encoded by FAS1, FAS2 and MSI1. Atfas1-4 mutants have reduced fertility due to a decrease in the number of cells that enter meiosis. Interestingly, the number of DNA double-strand breaks (DSBs), measured by scoring the presence of gammaH2AX, AtRAD51 and AtDMC1 foci, is higher than in wild-type (WT) plants, and meiotic recombination genes such AtCOM1/SAE2, AtBRCA1, AtRAD51 and AtDMC1 are overexpressed. An increase in DSBs in this mutant does not have a significant effect in the mean chiasma frequency at metaphase I, nor a different number of AtMLH1 nor AtMUS81 foci per cell compared to WT at pachytene. Nevertheless, this mutant does show a higher gene conversion (GC) frequency. To examine how an increase in DSBs influences meiotic recombination and synaptonemal complex (SC) formation, we analyzed double mutants defective for AtFAS1 and different homologous recombination (HR) proteins. Most showed significant increases in both the mean number of synapsis initiation points (SIPs) and the total length of AtZYP1 stretches in comparison with the corresponding single mutants. These experiments also provide new insight into the relationships between the recombinases in Arabidopsis, suggesting a prominent role for AtDMC1 versus AtRAD51 in establishing interhomolog interactions. In Arabidopsis an increase in the number of DSBs does not translate to an increase in the number of crossovers (COs) but instead in a higher GC frequency. We discuss different mechanisms to explain these results including the possible existence of CO homeostasis in plants. PMID- 26147461 TI - ZmMBD101 is a DNA-binding protein that maintains Mutator elements chromatin in a repressive state in maize. AB - In maize (Zea mays), as well as in other crops, transposable elements (TEs) constitute a great proportion of the genome. Chromatin modifications play a vital role in establishing transposon silencing and perpetuating the acquired repressive state. Nucleosomes associated with TEs are enriched for dimethylation of histone H3 at lysine 9 and 27 (H3K9me2 and H3K27me2, respectively), signals of repressive chromatin. Here, we describe a chromatin protein, ZmMBD101, involved in the regulation of Mutator (Mu) genes in maize. ZmMBD101 is localized to the nucleus and contains a methyl-CpG-binding domain (MBD) and a zinc finger CW (CW) domain. Transgenic lines with reduced levels of ZmMBD101 transcript present enhanced induction of Mu genes when plants are irradiated with UV-B. Chromatin immunoprecipitation analysis with H3K9me2 and H3K27me2 antibodies indicated that ZmMBD101 is required to maintain the levels of these histone repressive marks at Mu terminal inverted repeats (TIRs) under UV-B conditions. Although Mutator inactivity is associated with DNA methylation, cytosine methylation at Mu TIRs is not affected in ZmMBD101 deficient plants. Several plant proteins are predicted to share the simple CW-MBD domain architecture present in ZmMBD101. We hypothesize that plant CW-MBD proteins may also function to protect plant genomes from deleterious transposition. PMID- 26147462 TI - Correction: Baseline Levels and Temporal Stability of 27 Multiplexed Serum Cytokine Concentrations in Healthy Subjects. PMID- 26147463 TI - CD4+ CD56+ natural killer T-like cells secreting interferon-gamma are associated with incident coronary events. AB - BACKGROUND: CD3(+) CD56(+) natural killer T (NKT)-like cells are a subset of T cells characterized by expression of NK receptors and potent antitumour activity. It has also been suggested that they have a role in autoimmune disease, and levels of NKT-like cells are elevated in patients with coronary disease. OBJECTIVES: To investigate whether high levels of CD3(+) CD56(+) NKT-like cells are associated with an increased incidence of cardiovascular disease and a lower incidence of cancer. METHODS: This was a prospective study including 700 subjects participating in the baseline investigation of the Malmo Diet and Cancer study between 1991 and 1994. Leucocytes obtained at the baseline investigation and stored at -140 degrees C were thawed and CD3(+) CD56(+) cells analysed by flow cytometry. The incidence rates of cancer and coronary events during a mean follow up of 15 years were determined through national registers. RESULTS: Subjects in the lowest tertile of interferon (IFN)-gamma-expressing CD4(+) CD56(+) cells were found to have an increased risk of incidence of coronary events (log-rank test: P < 0.05). This association remained significant after controlling for age, sex, smoking, body mass index, hypertension, diabetes and the Th1/Th2 and Th1/Treg cell ratios in a Cox proportional hazards regression model (hazard ratio 1.98, 95% confidence interval 1.24-3.16), but not when the LDL/HDL ratio was included in the model. There were no associations between CD3(+) CD56(+) NKT-like cells and incident cancer. CONCLUSIONS: The present results could not confirm the hypothesis that low levels of CD3(+) CD56(+) NKT-like cells are associated with a higher incidence of cancer and a lower incidence of cardiovascular disease. However, we found that low levels of IFN-gamma-expressing CD3(+) CD4(+) CD56(+) NKT-like cells were associated with an increased incidence of coronary events and that this association may be dependent on lipoproteins. PMID- 26147464 TI - Effects of Fluid Treatment With Hydroxyethyl Starch on Renal Function in Patients With Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Recent reports have doubted the efficacy and safety of hydroxyethyl starch (HES) for volume resuscitation. HES has been reported to promote renal insufficiency particularly in sepsis and trauma patients. This analysis investigated the effects of HES 6% 130/0.4 for fluid therapy in patients with intact renal function who suffered aneurysmal subarachnoid hemorrhage (SAH). METHODS: This retrospective analysis included 107 patients and was conducted in the framework of a clinical trial assessing the efficacy of magnesium sulfate in SAH. Because magnesium is renally eliminated, patients with renal insufficiency had been excluded. Standard therapy after aneurysm occlusion included the daily administration of HES 6% 130/0.4. Serum and urine creatinine and fluid balance were measured daily. RESULTS: Patients received a daily mean of 1101+/-524 mL HES and 3353+/-1396 mL Ringer's solution. The highest creatinine values were recorded on day 3 after admission (0.88+/-0.25 mg/100 mL) and continuously decreased thereafter. In 6 patients, creatinine values temporarily increased by >0.3 mg/100 mL but recovered to admission values at the end of the observation period. CONCLUSIONS: Concerning renal function, the first days after SAH seem to be a vulnerable phase in which a variety of interventions are performed, including contrast-enhanced neuroradiologic procedures. In this period, HES 6% 130/0.4 should be administered with caution. However, no patient suffered from renal failure and required temporary or permanent renal replacement therapy. These results suggest that the administration of HES 6% 130/0.4 is safe in SAH patients without preexisting renal insufficiency. PMID- 26147465 TI - Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses. AB - Human adenovirus (HAdV) cause upper and lower respiratory tract infections. However, there are few large prospective studies focused on HAdVs acute infections requiring hospitalization. From 2005 to 2013 a prospective study was conducted on children admitted with acute respiratory infections. Specimens of nasopharyngeal aspirate were taken for virological study by PCR and clinical data was recorded. HAdV specimens were genotyped. Frequency and clinical course of HAdV infections were compared with RSV, rhinovirus (RV), human bocavirus (HBoV) and influenza in the same population. HAdV was detected in 403 cases of 2371 confirmed viral infections (17.2%) , of which 154 were single virus infections (38%). We genotyped 154 HAdVs. The most frequent genotypes were HAdV-3 (24%), HAdV-6 (21%), and HAdV-5 (20%). A total of 262 children had fever (64.9%); 194 suffered hypoxia (48%), and 147 presented infiltrate in chest x-rays (36.4%). The most frequent diagnoses were recurrent wheezing or asthma (51.7%), bronchiolitis (18.3 %), and pneumonia (11.9%), and 46 (11.4%) episodes required prolonged hospitalization (>7 days) due to the severity. Adenovirus single infections were compared with single infections of 598 RSV, 494 RV, 83 influenza and 78 HBoV. Significant clinical differences were found between HAdV, RSV and RV infections. PMID- 26147466 TI - Non-oral mucosal involvement of pemphigus vulgaris: Tzanck smear test as a handy diagnostic tool. PMID- 26147468 TI - Combined Approach for Government E-Tendering Using GA and TOPSIS with Intuitionistic Fuzzy Information. AB - As E-government continues to develop with ever-increasing speed, the requirement to enhance traditional government systems and affairs with electronic methods that are more effective and efficient is becoming critical. As a new product of information technology, E-tendering is becoming an inevitable reality owing to its efficiency, fairness, transparency, and accountability. Thus, developing and promoting government E-tendering (GeT) is imperative. This paper presents a hybrid approach combining genetic algorithm (GA) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) to enable GeT to search for the optimal tenderer efficiently and fairly under circumstances where the attributes of the tenderers are expressed as fuzzy number intuitionistic fuzzy sets (FNIFSs). GA is applied to obtain the optimal weights of evaluation criteria of tenderers automatically. TOPSIS is employed to search for the optimal tenderer. A prototype system is built and validated with an illustrative example from GeT to verify the feasibility and availability of the proposed approach. PMID- 26147467 TI - Congenital Anomalies in Children of Mothers Taking Antiepileptic Drugs with and without Periconceptional High Dose Folic Acid Use: A Population-Based Cohort Study. AB - BACKGROUND: Antenatal antiepileptic drug (AED) use has been found to be associated with increased major congenital anomaly (CA) risks. However whether such AED-associated risks were different according to periconceptional high dose (5mg daily) folic acid supplementation is still unclear. METHODS: We included 258,591 singleton live-born children of mothers aged 15-44 years in 1990-2013 from The Health Improvement Network, a large UK primary care database. We identified all major CAs according to the European Surveillance of Congenital Anomalies classification. Absolute risks and adjusted odds ratios (aOR) were calculated comparing children of mothers prescribed AEDs to those without such prescriptions, stratified by folic acid prescriptions around the time of conception (one month before conception to two months post-conception). RESULTS: CA risk was 476/10,000 in children of mothers with first trimester AEDs compared with 269/10,000 in those without AEDs equating to an aOR of 1.82, 95% confidence interval 1.30-2.56. The highest system-specific risks were for heart anomalies (198/10,000 and 79/10,000 respectively, aOR 2.49,1.47-4.21). Sodium valproate and lamotrigine were both associated with increased risks of any CA (aOR 2.63,1.46 4.74 and aOR 2.01,1.12-3.59 respectively) and system-specific risks. Stratification by folic acid supplementation did not show marked reductions in AED-associated risks (e.g. for CAs overall aOR 1.75, 1.01-3.03 in the high dose folic acid group and 1.94, 95%CI 1.21-3.13 in the low dose or no folic acid group); however, the majority of mothers taking AEDs only initiated high dose folic acid from the second month of pregnancy. CONCLUSIONS: Children of mothers with AEDs in the first trimester of pregnancy have a 2-fold increased risk of major CA compared to those unexposed. We found no evidence that prescribed high dose folic acid supplementation reduced such AED-associated risks. Although statistical power was limited, prescribing of folic acid too late for it to be effective during the organogenic period or selective prescribing to those with more severe morbidity may explain these findings. PMID- 26147469 TI - Therapeutic Effects of Treatment with Anti-TLR2 and Anti-TLR4 Monoclonal Antibodies in Polymicrobial Sepsis. AB - INTRODUCTION: Toll-like receptors (TLRs) play an important role in the recognition of microbial products and in host defense against infection. However, the massive release of inflammatory mediators into the bloodstream following TLR activation following sepsis is thought to contribute to disease pathogenesis. METHODS: Here, we evaluated the effects of preventive or therapeutic administration of monoclonal antibodies (mAbs) targeting either TLR2 or TLR4 in a model of severe polymicrobial sepsis induced by cecal ligation and puncture in mice. RESULTS: Pre-treatment with anti-TLR2 or anti-TLR4 mAb alone showed significant protection from sepsis-associated death. Protective effects were observed even when the administration of either anti-TLR2 or anti-TLR4 alone was delayed (i.e., 3 h after sepsis induction). Delayed administration of either mAb in combination with antibiotics resulted in additive protection. CONCLUSION: Although attempts to translate preclinical findings to clinical sepsis have failed so far, our preclinical experiments strongly suggest that there is a sufficient therapeutic window within which patients with ongoing sepsis could benefit from combined antibiotic plus anti-TLR2 or anti-TLR4 mAb treatment. PMID- 26147471 TI - Minimal Prolongation of Prothrombin Time with Extended Exposure to Argatroban. AB - In the setting of acute heparin-induced thrombocytopenia (HIT), argatroban is one of the initial anticoagulants of choice, which is eventually bridged to warfarin over a period of 5 or more days. Argatroban prolongs prothrombin time (PT) and increases international normalized ratio (INR). However, the effects of prolonged argatroban exposure on the PT and INR are not known. We describe an unusual case of prolonged argatroban treatment in a patient with heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) resulting in a minimal elevation of the INR. The patient received a total of 58 days of argatroban and was resistant to warfarin therapy, requiring a 13-day bridge to achieve a therapeutic INR of 2.0 to 3.0. Ultimately, argatroban was successfully transitioned to warfarin therapy when the INR was 2.7 on both agents, producing the confirmatory true INR of 2.4. Argatroban and warfarin cotherapy did not increase the INR beyond 4.0 after prolonged argatroban exposure. Clinicians should consider this unusual response in other cases of prolonged argatroban use, and monitor INR carefully during warfarin and argatroban cotherapy. The use of other methods to monitor anticoagulant therapy, such as chromogenic factor X assay (CFX), may be helpful in this setting. PMID- 26147470 TI - A Phox2b BAC Transgenic Rat Line Useful for Understanding Respiratory Rhythm Generator Neural Circuitry. AB - The key role of the respiratory neural center is respiratory rhythm generation to maintain homeostasis through the control of arterial blood pCO2/pH and pO2 levels. The neuronal network responsible for respiratory rhythm generation in neonatal rat resides in the ventral side of the medulla and is composed of two groups; the parafacial respiratory group (pFRG) and the pre-Botzinger complex group (preBotC). The pFRG partially overlaps in the retrotrapezoid nucleus (RTN), which was originally identified in adult cats and rats. Part of the pre inspiratory (Pre-I) neurons in the RTN/pFRG serves as central chemoreceptor neurons and the CO2 sensitive Pre-I neurons express homeobox gene Phox2b. Phox2b encodes a transcription factor and is essential for the development of the sensory-motor visceral circuits. Mutations in human PHOX2B cause congenital hypoventilation syndrome, which is characterized by blunted ventilatory response to hypercapnia. Here we describe the generation of a novel transgenic (Tg) rat harboring fluorescently labeled Pre-I neurons in the RTN/pFRG. In addition, the Tg rat showed fluorescent signals in autonomic enteric neurons and carotid bodies. Because the Tg rat expresses inducible Cre recombinase in PHOX2B-positive cells during development, it is a potentially powerful tool for dissecting the entire picture of the respiratory neural network during development and for identifying the CO2/O2 sensor molecules in the adult central and peripheral nervous systems. PMID- 26147472 TI - Grp78 Is Critical for Amelogenin-Induced Cell Migration in a Multipotent Clonal Human Periodontal Ligament Cell Line. AB - Periodontal ligament stem cells (PDLSCs) are known to play a pivotal role in regenerating the periodontium. Amelogenin, which belongs to a family of extracellular matrix (ECM) proteins, is a potential bioactive molecule for periodontal regenerative therapy. However, its downstream target molecules and/or signaling patterns are still unknown. Our recent proteomic study identified glucose-regulated protein 78 (Grp78) as a new amelogenin-binding protein. In this study, we demonstrate, for the first time, the cellular responses induced by the biological interaction between amelogenin and Grp78 in the human undifferentiated PDL cell line 1-17, which possesses the most typical characteristics of PDLSCs. Confocal co-localization experiments revealed the internalization of recombinant amelogenin (rM180) via binding to cell surface Grp78, and the endocytosis was inhibited by the silencing of Grp78 in 1-17 cells. Microarray analysis indicated that rM180 and Grp78 regulate the expression profiles of cell migration associated genes in 1-17 cells. Moreover, Grp78 overexpression enhanced rM180 induced cell migration and adhesion without affecting cell proliferation, while silencing of Grp78 diminished these activities. Finally, binding of rM180 to Grp78 promoted the formation of lamellipodia, and the simultaneous activation of Rac1 was also demonstrated by NSC23766, a widely accepted Rac1 inhibitor. These results suggest that Grp78 is essential for enhancing amelogenin-induced migration in 1-17 cells. The biological interaction of amelogenin with Grp78 offers significant therapeutic potential for understanding the biological components and specific functions involved in the signal transduction of amelogenin-induced periodontal tissue regeneration. PMID- 26147474 TI - A thoroughly validated spreadsheet for calculating isotopic abundances (2H, 17O, 18O) for mixtures of waters with different isotopic compositions. AB - RATIONALE: Oxygen and hydrogen stable isotopes are widely used tracers for studies on naturally occurring and laboratory mixtures of isotopically different waters. Although the mixing calculations are straightforward to perform, there are ample possibilities to make mistakes, especially when dealing with a large number of mixed fluids. To facilitate isotope mixing calculations and to avoid computational mistakes, a flexible tool to carry out these calculations is in demand. METHODS: We developed, in three independent efforts, spreadsheets to carry out the mixing calculations for a combination of waters with different isotopic compositions using the isotope mass balance equation. We validated our calculations by comparison of the results of the three spreadsheets for a large number of test calculations. For all the cases, we obtained identical results down to the 12(th) to 14(th) significant digit. RESULTS: We present a user friendly, thoroughly validated spreadsheet for calculating (2) H, (17) O and (18) O stable isotopic abundances and respective isotope delta values for mixtures of waters with arbitrary isotopic compositions. The spreadsheet allows the mixing of up to 10 different waters, of which up to five can be specified using their isotopic abundances and up to five others using their isotope delta values. The spreadsheet is implemented in Microsoft Excel and is freely available from our research groups' websites. CONCLUSIONS: The present tool will be applicable in the production and characterization of singly and doubly labeled water (DLW) mother solutions, the analysis of isotope dilution measurements, the deduction of unknown isotope values of constituents for mixtures of natural waters, and many other applications. PMID- 26147473 TI - HIV Incidence and Spatial Clustering in a Rural Area of Southern Mozambique. AB - BACKGROUND: Monitoring the HIV epidemic in a defined population is critical for planning treatment and preventive strategies. This is especially important in sub Saharan Africa, which harbours the highest burden of the disease. OBJECTIVE: To estimate HIV incidence in adults aged 18-47 years old and to investigate spatial variations of HIV prevalence in Manhica, a semi-rural area of southern Mozambique. METHODS: Two cross-sectional community-based surveys were conducted in 2010 and 2012 to determine HIV prevalence. Individual participants were randomly selected from the demographic surveillance system in place in the area and voluntary HIV counselling and testing was offered at the household level. HIV incidence was calculated using prevalence estimates from the two sero-surveys. Each participant's household was geocoded using a global information system. The Spatial Scan Statistics programme was used to identify areas with disproportionate excess in HIV prevalence. RESULTS: A total of 1511 adults were tested. The estimated HIV prevalence in the community was 39.9% in 2010 and 39.7% in 2012. The overall HIV incidence was 3.6 new infections per 100 person-years at risk (PYAR) [95CI 1.56; 7.88], assuming stable epidemic conditions, and tended to be higher in women (4.9/100 PYAR [95CI 1.74; 11.85]) than in men (3.2/PYAR [95CI 1.36; 9.92]). One cluster with significant excess HIV prevalence was identified at the same geographic location in both surveys. This cluster had an HIV prevalence of 79.0% in 2010 and 52.3% in 2012. CONCLUSIONS: The findings of these first individually-randomised community-HIV sero-surveys conducted in Mozambique reinforce the need to combine HIV incidence estimates and research on micro geographical infection patterns to guide and consolidate effective prevention strategies. PMID- 26147475 TI - Isotopic composition of sheep wool records seasonality of climate and diet. AB - RATIONALE: Hair keratin is a very important material in ecological and archaeological studies because it grows continuously, can be obtained non invasively, does not require extensive processing prior to analysis and can be found in archaeological sites. Only a few studies have examined seasonal variations in hair isotope values, and there is no published dataset examining the isotope variability recorded in the keratinous tissues of stationary (i.e., non-migrating) domestic mammals. METHODS: Thirty-six Irish sheep were sampled in eight farms every three months between September 2006 and June 2007. A shearing strategy was adopted to sample only the most recently grown wool in order to represent an average of the summer, autumn, winter and spring conditions. The stable isotope ratios of the ground samples were measured using two different stable isotope mass spectrometers operated in dual-inlet (C, N) and continuous flow (O, H) mode. RESULTS: Wool O isotope ratios are a good proxy for seasonal variability in climate and can be used to anchor a chronology independently of other isotope records (C, N) that are influenced by diet or physiology. By contrast, interpretation of seasonal variations in hair H isotope composition in terms of climate is more complex probably due to the influence of dietary H. The C and N isotope values of grass-fed animals varied seasonally, probably reflecting the annual cycle of seasonal variation in grass isotope values. The highest delta(13) C values were measured in summer-grown wool, while the highest delta(15) N values were measured in winter-grown wool. Supplementation of the sheep diet with concentrates was detected easily and was marked by an increase in delta(13) C values and a decrease in delta(15) N values in winter-grown wool. CONCLUSIONS: The present study demonstrates that time-resolved sampling and stable isotope ratio analysis of sheep wool can be used to identify short-term changes in diet and climate and therefore offer a tool to examine a wide variety of present and past husbandry practices. PMID- 26147476 TI - Application of liquid chromatography/electrospray ionization tandem mass spectrometry for the elucidation of hydroxyl radical oxidation of metsulfuron methyl and related sulfonylurea pesticide products: evidence for the triazine skeleton scission. AB - RATIONALE: Sulfonylureas are among the most important class of antidiabetic and herbicides. Solar light excitation and Advanced Oxidation Processes may result in the formation of a wide array of products owing to the relative complex structure. These products, that should be identified, may present a more toxic effect than the parent compound. METHODS: Liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (LC/ESI-QTOFMS) with accurate mass determination emerges as a valuable technique for the precise elucidation of all possible byproducts. The hydroxyl radical was generated by excitation of the iron(III) aquacomplex [Fe(H(2)O)OH](2+) and hydrogen peroxide at pH 3.5. Three different sulfonylureas were studied: metsulfuron methyl, cinosulfuron and thifensulfuron methyl. RESULTS: Several products owing to the reactivity of hydroxyl radicals with sulfonylurea were obtained. They arise from scission of the sulfonylurea bridge, hydroxylation of the aromatic ring, demethylation of the methoxy group and more importantly and unequivocally from the rupture of the triazine skeleton. To reach such scission, a primary demethylation of the methoxy group on the triazine moiety seems to act as a precursor process. Such a process was observed with the three studied sulfonylurea compounds. CONCLUSIONS: The reported results demonstrated the usefulness of accurate mass measurements undertaken by LC/ESI-QTOFMS for structural elucidation of the unknown byproducts that were generated during hydroxyl radical reactions with some sulfonylureas. It has been possible herein to identify the structures of products arising from the opening of the recalcitrant triazine structure via hydrolysis processes in acidic solutions. PMID- 26147477 TI - Improved accuracy and precision in delta15 NAIR measurements of explosives, urea, and inorganic nitrates by elemental analyzer/isotope ratio mass spectrometry using thermal decomposition. AB - RATIONALE: Elemental analyzer systems generate N(2) and CO(2) for elemental composition and isotope ratio measurements. As quantitative conversion of nitrogen in some materials (i.e., nitrate salts and nitro-organic compounds) is difficult, this study tests a recently published method - thermal decomposition without the addition of O(2) - for the analysis of these materials. METHODS: Elemental analyzer/isotope ratio mass spectrometry (EA/IRMS) was used to compare the traditional combustion method (CM) and the thermal decomposition method (TDM), where additional O(2) is eliminated from the reaction. The comparisons used organic and inorganic materials with oxidized and/or reduced nitrogen and included ureas, nitrate salts, ammonium sulfate, nitro esters, and nitramines. Previous TDM applications were limited to nitrate salts and ammonium sulfate. The measurement precision and accuracy were compared to determine the effectiveness of converting materials containing different fractions of oxidized nitrogen into N(2). RESULTS: The delta(13) C(VPDB) values were not meaningfully different when measured via CM or TDM, allowing for the analysis of multiple elements in one sample. For materials containing oxidized nitrogen, (15) N measurements made using thermal decomposition were more precise than those made using combustion. The precision was similar between the methods for materials containing reduced nitrogen. The %N values were closer to theoretical when measured by TDM than by CM. The delta(15) N(AIR) values of purchased nitrate salts and ureas were nearer to the known values when analyzed using thermal decomposition than using combustion. CONCLUSIONS: The thermal decomposition method addresses insufficient recovery of nitrogen during elemental analysis in a variety of organic and inorganic materials. Its implementation requires relatively few changes to the elemental analyzer. Using TDM, it is possible to directly calibrate certain organic materials to international nitrate isotope reference materials without off-line preparation. PMID- 26147478 TI - Applying multiple proteases to direct digestion of hundred-scale cell samples for proteome analysis. AB - RATIONALE: Analyzing the proteome on the scale of only several hundred cells with mass spectrometry has great significance for applications with limited sample amounts. We applied multiple proteases to the direct digestion of cells and compared the identified proteins both qualitatively and quantitatively. METHODS: Three hundred cells were directly digested by trypsin, chymotrypsin, or the combination of trypsin and chymotrypsin. The peptides were identified using a LTQ Orbitrap XL, and data were analyzed using MaxQuant software. RESULTS: Different proteases produced different identified protein numbers. Trypsin proved to be the best choice for generating the largest protein number, while other proteases complemented the identification results of trypsin by increasing protein sequence coverage. Concerning the quantitative perspective, using trypsin would produce the biggest number of proteins quantifiable by intensity-based absolute quantification (iBAQ). CONCLUSIONS: When hundred-scale cell samples are analyzed, an optimum choice of proteases should be made to realize different analytical objectives. PMID- 26147479 TI - Gas-phase fragmentation of deprotonated tryptophan and its clusters [Trpn -H]- induced by different activation methods. AB - RATIONALE: Non-covalent amino acid clusters are the subject of intense research in diverse areas including peptide bond formation studies or the determination of proton affinities or methylating abilities of amino acids. However, most of the research has focused on positive ions and little is known about anionic clusters. METHODS: Fragmentation reactions of deprotonated tryptophan (Trp), [Trp-H](-) and Trp singly deprotonated non-covalently bound clusters [Trp(n) -H](-), n = 2, 3, 4, were investigated using low-energy collision-induced dissociation (CID) with He atoms, high-energy CID with Na atoms, and electron-induced dissociation (EID) with 20-35 eV electrons. Fragmentation of the monomeric Trp anion, where all labile hydrogens were exchanged for deuterium [d(4) -Trp-D](-), was investigated using low-energy CID and EID, in order to shed light on the dissociation mechanisms. RESULTS: The main fragmentation channel for Trp cluster anions, [Trp(n) -H](-), n >1, is the loss of the neutral monomer. The fragmentation of the deprotonated Trp monomer induced by electrons resembles the fragmentation induced by high-energy collisions through electronic excitation of the parent. However, the excitation must precede in a different way, shown through only monomer loss from larger clusters, n >1, in case of EID, but intracluster chemistry in the case of high-energy CID. CONCLUSIONS: The anion of the indole ring C(8)H(6) N(-) has been identified in the product ion spectra of [Trp(n) -H]( ) using all activation methods, thus providing a diagnostic marker ion. No evidence was found for formation of peptide bonds as a route to prebiotic peptides in the fragmentation reactions of these singly deprotonated Trp cluster ions. PMID- 26147480 TI - Metals and possible sources of lead in aerosols at the Dinghushan nature reserve, southern China. AB - RATIONALE: Aerosols play an important role in depositing metals into forest ecosystems. Better understanding of forest aerosols with regard to their metal content and their possible sources is of great significance for air quality and forest health. METHODS: Particulate matter with an aerodynamic diameter less than 2.5 um (PM(2.5)) in aerosols was collected every month for 20 months using moderate-volume samplers in the Dinghushan (DHS) nature reserve in southern China. The concentrations of metals (Al, Cd, Mn, Ni, Pb, and Zn) as well as the Pb isotopic ratios in the PM(2.5) samples were measured by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Moderate pollution with aerosol PM(2.5) was detected at the DHS nature reserve with the air mass from mainland China being the predominant PM(2.5) source. The high enrichment factors (EFs) for the heavy metals Pb, Cd, and Zn, as well as the PM(2.5) mass concentrations, coupled with backward trajectory analysis, indicated the anthropogenic origins of the PM(2.5) and of the heavy metals in the PM(2.5). The Pb isotopic ratios revealed the contributions from various Pb sources, which varied between seasons. CONCLUSIONS: Industrial emissions and automobile exhaust from the Pearl River Delta (PRD) primarily contributed to the anthropogenic Pb in PM(2.5), although there was occasionally a contribution from coal combustion during the wet season. Pb isotopic ratios analyses are helpful for air quality assessment and Pb source tracing. PMID- 26147481 TI - Gas-phase conformations of capistruin - comparison of lasso, branched-cyclic and linear topologies. AB - RATIONALE: Capistruin is a peptide synthesized by Burkholderia thailandensis E264, which displays a lasso topology. This knot-like structure confers interesting properties to peptides (e.g. antibacterial). Therefore, it is important to evaluate the sensitivity of structural characterization methods to such topological constraints. METHODS: Ion mobility mass spectrometry (IMS-MS) experiments, using both drift tube and travelling wave instruments, were performed on lasso capistruin and on peptides with the same sequence, but displaying a branched-cyclic (un-threaded) or linear topology. Molecular dynamics (MD) simulations were then performed to further interpret the IMS results in terms of conformation. RESULTS: The collision cross sections (CCSs) measured via IMS for the different forms of capistruin were found to be similar, despite their different topologies for the doubly charged species, but significant differences arise as the charge state is increased. MD simulations for the doubly charged linear peptide were consistent with the hypothesis that salt bridges are present in the gas phase. Moreover, through CCS measurements for peptides with site specific mutations, the arginine residue at position 11 was found to play a major role in the stabilization of compact structures for the linear peptide. CONCLUSIONS: Differences in peptide topologies did not yield marked signatures in their respective IMS spectra. Such signatures were only visible for relatively high charge states, that allow Coulomb repulsion to force unfolding. At low charge states, the topologically unconstrained linear form of capistruin was found to adopt charge solvation-constrained structures, possibly including salt bridges, with CCSs comparable to those measured for the topologically constrained lasso form. PMID- 26147482 TI - Electrospray droplet impact secondary ion mass spectrometry using a vacuum electrospray source. AB - RATIONALE: In electrospray droplet impact (EDI) developed in our laboratory, an atmospheric pressure electrospray source has been used. To increase the ion beam intensity and reduce the evacuation load, a vacuum electrospray cluster ion source using a silica capillary was developed. METHODS: A silica capillary with a tip inner diameter of 8 um was used for vacuum electrospray using aqueous 10% methanol. To stabilize the flow rate of the liquid for nano-electrospray, a home made constant pressure liquid pump was also developed. RESULTS: By using the silica tip nano-electrospray emitter and a constant pressure pump, stable electrospray with flow rate of 22 nL/min was realized without using any heating system such as laser irradiation. Comparative study of mass spectra obtained by atmospheric pressure EDI (A-EDI) and vacuum EDI (V-EDI) was made for various samples such as thermometer molecule, peptide, polystyrene, Alq(3), NPD, C(60), indium, and SiO(2). V-EDI showed slightly milder ionization than A-EDI. CONCLUSIONS: Because V-EDI gave higher target current (5-10 nA) than A-EDI (a few nA at most), V-EDI secondary ion mass spectrometry (SIMS) would be a useful technique for the surface and interface analysis. PMID- 26147483 TI - Thermodynamic study of gaseous tin molybdates by high-temperature mass spectrometry. AB - RATIONALE: Molybdenum and tin are components of various construction materials which are often used at high temperature and in an oxidizing atmosphere. Oxides of molybdenum and tin, with their high reactivity, can, in their turn, form a number of gaseous compounds. To predict the possibility of the existence of gaseous associates formed by tin and molybdenum oxides it is important to know their thermodynamic characteristics. Until the present investigation only a few gaseous salts of tin were known. METHODS: High-temperature Knudsen effusion mass spectrometry was used to determine the partial pressures of vapor species over the SnO(2) -MoO(3) system. The formation enthalpies of gaseous SnMoO(4), Sn(2) MoO(5) and SnMo(2)O(7) were derived. Measurements were performed with a MS-1301 mass spectrometer. Vaporization was carried out using a molybdenum effusion cell containing the samples under study and pure gold as the reference substance. A theoretical study of gaseous tin molybdates was performed by several quantum chemical methods: wave function based explicitly correlated F12 methods and DFT M0(6) methods. RESULTS: In the temperature range of 1200-1400 K, SnO, Sn(2)O(2), SnMoO(4), Sn(2) MoO(5), SnMo(2)O(7), MoO(3), Mo(2)O(6) and Mo(3)O(9) were found to be the main vapor species over the samples studied. On the basis of the equilibrium constants of gaseous reactions, the standard formation enthalpies of gaseous SnMoO(4) (-699 +/- 29 kJ/mol), Sn(2) MoO(5) (-1001 +/- 38 kJ/mol) and SnMo(2)O(7) (-1456 +/- 60 kJ/mol) at 298 K were determined. Energetically favorable structures were found and vibrational frequencies were evaluated in the harmonic approximation. CONCLUSIONS: The stability of gaseous species, SnMoO(4), Sn(2) MoO(5) and SnMo(2)O(7), was confirmed by high-temperature mass spectrometry. A number of gas-phase reactions involving tin-containing gaseous salts were studied. The enthalpies of reactions of gaseous tin molybdates were evaluated theoretically and the obtained values are in agreement with those obtained experimentally. PMID- 26147484 TI - Liquid chromatography/tandem mass spectrometry study of forced degradation of azilsartan medoxomil potassium. AB - RATIONALE: Azilsartan medoxomil potassium (AZM) is a new antihypertensive drug introduced in the year 2011. The presence of degradation products not only affects the quality, but also the safety aspects of the drug. Thus, it is essential to develop an efficient analytical method which could be useful to selectively separate and identify the degradation products of azilsartan medoxomil potassium. METHODS: AZM was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions. Separation of the drug and degradation products was achieved by a liquid chromatography (LC) method using an Acquity UPLC((r)) C18 CSH column with mobile phase consisting of 0.02% trifluoroacetic acid and acetonitrile using a gradient method. Identification and characterization of the degradation products was carried out using LC/electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS). RESULTS: A total of five degradation products (DP 1 to DP 5) were formed under various stress conditions and their structures were proposed with the help of tandem mass spectrometry (MS/MS) experiments and accurate mass data. A common degradation product (DP 4) was observed under all the degradation conditions. DP 1, DP 2 and DP 5 were observed under acid hydrolytic conditions whereas DP 3 was observed under alkaline conditions. CONCLUSIONS: AZM was found to degrade under hydrolytic, oxidative and photolytic stress conditions. The structures of all the degradation products were proposed. The degradation pathway for the formation of degradation products was also hypothesized. A selective method was developed to quantify the drug in the presence of degradation products which is useful to monitor the quality of AZM. PMID- 26147485 TI - Variability in the routing of dietary proteins and lipids to consumer tissues influences tissue-specific isotopic discrimination. AB - RATIONALE: The eco-physiological mechanisms that govern the incorporation and routing of macronutrients from dietary sources into consumer tissues determine the efficacy of stable isotope analysis (SIA) for studying animal foraging ecology. We document how changes in the relative amounts of dietary proteins and lipids affect the metabolic routing of these macronutrients and the consequent effects on tissue-specific discrimination factors in domestic mice using SIA. We also examine the effects of dietary macromolecular content on a commonly used methodological approach: lipid extraction of potential food sources. METHODS: We used carbon ((13) C) and nitrogen ((15) N) isotopes to examine the routing of carbon from dietary proteins and lipids that were used by mice to biosynthesize hair, blood, muscle, and liver. Growing mice were fed one of four diet treatments in which the total dietary content of C4 -based lipids (delta(13) C = -14.50/00) and C(3) -based proteins (delta(13) C = -270/00) varied inversely between 5% and 40%. RESULTS: The delta(13) C values of mouse tissues increased by approximately 2-60/00 with increasing dietary lipid content. The difference in delta(13) C values between mouse tissues and bulk diet ranged from 0.1 +/- 1.50/00 to 2.3 +/- 0.60/00 for all diet treatments. The mean (+/-SD) difference between the delta(13) C values of mouse tissues and dietary protein varied systematically among tissues and ranged from 3.1 +/- 0.10/00 to 4.5 +/- 0.60/00 for low fat diets and from 5.4 +/- 0.40/00 to 10.5 +/- 7.30/00 for high fat diets. CONCLUSIONS: Mice used some fraction of their dietary lipid carbon to synthesize tissue proteins, suggesting flexibility in the routing of dietary macromolecules to consumer tissues based on dietary macromolecular availability. Consequently, all constituent dietary macromolecules, not just protein, should be considered when determining the relationship between diets and consumer tissues using SIA. In addition, in cases where animals consume diets with high lipid contents, non lipid-extracted prey samples should be analyzed to estimate diets using SIA. PMID- 26147486 TI - Building up strain in colloidal metal nanoparticle catalysts. AB - The focus on surface lattice strain in nanostructures as a fundamental research topic has gained momentum in recent years as scientists investigated its significant impact on the surface electronic structure and catalytic properties of nanomaterials. Researchers have begun to tell a more complete story of catalysis from a perspective which brings this concept to the forefront of the discussion. The nano-'realm' makes the effects of surface lattice strain, which acts on the same spatial scales, more pronounced due to a higher ratio of surface to bulk atoms. This is especially evident in the field of metal nanoparticle catalysis, where displacement of atoms on surfaces can significantly alter the sorption properties of molecules. In part, the concept of strain-engineering for catalysis opened up due to the achievements that were made in the synthesis of a more sophisticated nanoparticle library from an ever-expanding set of methodologies. Developing synthesis methods for metal nanoparticles with well defined and strained architectures is a worthy goal that, if reached, will have considerable impact in the search for catalysts. In this review, we summarize the recent accomplishments in the area of surface lattice-strained metal nanoparticle synthesis, framing the discussion from the important perspective of surface lattice strain effects in catalysis. PMID- 26147487 TI - Cognitive Behavioral Therapy for Insomnia Comorbid With Psychiatric and Medical Conditions: A Meta-analysis. AB - IMPORTANCE: Cognitive behavioral therapy for insomnia (CBT-I) is the most prominent nonpharmacologic treatment for insomnia disorders. Although meta analyses have examined primary insomnia, less is known about the comparative efficacy of CBT-I on comorbid insomnia. OBJECTIVE: To examine the efficacy of CBT I for insomnia comorbid with psychiatric and/or medical conditions for (1) remission from insomnia; (2) self-reported sleep efficiency, sleep onset latency, wake after sleep onset, total sleep time, and subjective sleep quality; and (3) comorbid symptoms. DATA SOURCES: A systematic search was conducted on June 2, 2014, through PubMed, PsycINFO, the Cochrane Library, and manual searches. Search terms included (1) CBT-I or CBT or cognitive behavioral [and its variations] or behavioral therapy [and its variations] or behavioral sleep medicine or stimulus control or sleep restriction or relaxation therapy or relaxation training or progressive muscle relaxation or paradoxical intention; and (2) insomnia or sleep disturbance. STUDY SELECTION: Studies were included if they were randomized clinical trials with at least one CBT-I arm and had an adult population meeting diagnostic criteria for insomnia as well as a concomitant condition. Inclusion in final analyses (37 studies) was based on consensus between 3 authors' independent screenings. DATA EXTRACTION AND SYNTHESIS: Data were independently extracted by 2 authors and pooled using a random-effects model. Study quality was independently evaluated by 2 authors using the Cochrane risk of bias assessment tool. MAIN OUTCOMES AND MEASURES: A priori main outcomes (ie, clinical sleep and comorbid outcomes) were derived from sleep diary and other self-report measures. RESULTS: At posttreatment evaluation, 36.0% of patients who received CBT-I were in remission from insomnia compared with 16.9% of those in control or comparison conditions (pooled odds ratio, 3.28; 95% CI, 2.30-4.68; P < .001). Pretreatment and posttreatment controlled effect sizes were medium to large for most sleep parameters (sleep efficiency: Hedges g = 0.91 [95% CI, 0.74 to 1.08]; sleep onset latency: Hedges g = 0.80 [95% CI, 0.60 to 1.00]; wake after sleep onset: Hedges g = 0.68; sleep quality: Hedges g = 0.84; all P < .001), except total sleep time. Comorbid outcomes yielded a small effect size (Hedges g = 0.39 [95% CI, 0.60 0.98]; P < .001); improvements were greater in psychiatric than in medical populations (Hedges g = 0.20 [95% CI, 0.09-0.30]; chi2 test for interaction = 12.30; P < .001). CONCLUSIONS AND RELEVANCE: Cognitive behavioral therapy for insomnia is efficacious for improving insomnia symptoms and sleep parameters for patients with comorbid insomnia. A small to medium positive effect was found across comorbid outcomes, with larger effects on psychiatric conditions compared with medical conditions. Large-scale studies with more rigorous designs to reduce detection and performance bias are needed to improve the quality of the evidence. PMID- 26147488 TI - Direct Imaging of Highly Anisotropic Photogenerated Charge Separations on Different Facets of a Single BiVO4 Photocatalyst. AB - Spatially resolved surface photovoltage spectroscopy (SRSPS) was employed to obtain direct evidence for highly anisotropic photogenerated charge separation on different facets of a single BiVO4 photocatalyst. Through the controlled synthesis of a single crystal with preferentially exposed {010} facets, highly anisotropic photogenerated hole transfer to the {011} facet of single BiVO4 crystals was observed. The surface photovoltage signal intensity on the {011} facet was 70 times stronger than that on the {010} facets. The influence of the built-in electric field in the space charge region of different facets on the anisotropic photoinduced charge transfer in a single semiconductor crystal is revealed. PMID- 26147489 TI - The role of stoichiometric flexibility in modelling forest ecosystem responses to nitrogen fertilization. AB - The response of the forest carbon (C) balance to changes in nitrogen (N) deposition is uncertain, partly owing to diverging representations of N cycle processes in dynamic global vegetation models (DGVMs). Here, we examined how different assumptions about the degree of flexibility of the ecosystem's C : N ratios contribute to this uncertainty, and which of these assumptions best correspond to the available data. We applied these assumptions within the framework of a DGVM and compared the results to responses in net primary productivity (NPP), leaf N concentration, and ecosystem N partitioning, observed at 22 forest N fertilization experiments. Employing flexible ecosystem pool C : N ratios generally resulted in the most convincing model-data agreement with respect to production and foliar N responses. An intermediate degree of stoichiometric flexibility in vegetation, where wood C : N ratio changes were decoupled from leaf and root C : N ratio changes, led to consistent simulation of production and N cycle responses to N addition. Assuming fixed C : N ratios or scaling leaf N concentration changes to other tissues, commonly assumed by DGVMs, was not supported by reported data. Between the tested assumptions, the simulated changes in ecosystem C storage relative to changes in C assimilation varied by up to 20%. PMID- 26147490 TI - Cytotoxic Homoisoflavones from the Bulbs of Bellevalia eigii. AB - Eight new and 10 known compounds were isolated from an organic extract of the bulbs of Bellevalia eigii as part of a search for anticancer leads from native plants of Jordan. Of these, the series of 16 homoisoflavonoids (1-16) comprise the seven new analogues 7-O-methyl-3'-hydroxy-3,9-dihydropunctatin (3), 6-hydroxy 7-O-methyl-3,9-dihydropunctatin (6), 7,4'-di-O-methyl-3'-hydroxy-3,9 dihydropunctatin (9), 7-O-methylpunctatin (10), 7-O-methyl-3'-hydroxypunctatin (13), 5-hydroxy-7,8-dimethoxychroman-4-one (14), and 7-O-methyl-8-demethoxy-3 hydroxy-3,9-dihydropunctatin (15). The known ferulic acid-derived acrylamide (17) and the new methylthioacrylate bellegimycin (18) are also reported. The structures were elucidated using a set of spectroscopic and spectrometric techniques; the absolute configurations of compounds 1-9, 15, and 16 were determined using ECD spectroscopy, while a modified Mosher's ester method was used for compound 18. Optical rotation data for the known compounds 1, 2, and 8 are reported here for the first time. The cytotoxic activities of all compounds were evaluated using the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compounds 4 and 9 were the most potent on the latter cell line, with IC50 values of 1.0 and 1.1 MUM, respectively. Compounds 1-18 were assessed for antimicrobial activity using a collection of bacteria and fungi; compounds 4 and 12 showed promising activity against the bacterium Mycobacterium smegmatis with MIC values of 17 and 24 MUg/mL, respectively. PMID- 26147491 TI - Surface-enhanced IR absorption spectroscopy of the KcsA potassium channel upon application of an electric field. AB - Surface-enhanced IR absorption spectroscopy (SEIRAS) is a powerful tool for studying the structure of molecules adsorbed on an electrode surface (ATR-SEIRA). Coupled with an electrochemical system, structural changes induced by changes in the electric field can be detected. All the membrane proteins are subjected to the effect of membrane electric field, but conformational changes at different membrane potentials and their functional relevance have not been studied extensively except for channel proteins. In this contribution, background information of potential-dependent functional and structural changes of a prototypical channel, the KcsA channel, is summarized, and SEIRAS applied to the KcsA channel under the application of the potential is shown. The potassium channels allow K(+) to permeate selectively through the structural part called the selectivity filter, in which dehydrated K(+) ions interact with backbone carbonyls. In the absence of K(+), the selectivity filter undergoes conformational changes to the non-conductive collapsed conformation. To apply the electric field, the KcsA channels were fixed on the gold surface in either upside or reverse orientation. The SEIRA spectrum in K(+) or Na(+) solution revealed both backbone structural changes and local changes in the OCO-carboxylate groups. Upon application of the negative electric field, the spectrum of OCO was enhanced only in the K(+) solution. These results indicate that the negative electric field accumulates local K(+) concentration, which turned the collapsed filter to the conductive conformation. ATR-SEIRA serves as an unprecedented experimental system for examining membrane proteins under an electric field. PMID- 26147492 TI - Intraductal biliopancreatic imaging: European Society of Gastrointestinal Endoscopy (ESGE) technology review. AB - This technology review expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) on the available techniques for intraductal biliopancreatic imaging. The three cholangioscopy techniques are described: the "dual-operator" and " single-operator" mother-baby approaches using dedicated instruments, and the "direct" technique using currently available ultrathin gastroscopes. The mother-baby method is standardized and reproducible, while direct cholangioscopy is technically demanding and its safety requires further evaluation. As well as direct visualization of the bile ducts, cholangioscopy has the further advantage of allowing targeted biopsy. Image quality is still suboptimal for single-operator cholangioscopy, while the other techniques have achieved adequately detailed imaging. The costs of mother-baby cholangioscopy are high and its application in clinical practice should be restricted to selected cases (i.e. indeterminate biliary strictures/intraluminal lesions, difficult biliary stones) and to the setting of tertiary care centers. Peroral pancreatoscopy may find an indication in situations where other imaging modalities (mainly EUS) are inconclusive (i.e. delineation of main duct intraductal papillary mucinous neoplasia extension, sampling of indeterminate main pancreatic duct strictures). Intraductal ultrasonography (IDUS) has a poorer performance than EUS in the staging of pancreatic malignancies and can increase the risk of pancreatitis. A promising indication for IDUS could be the evaluation of indeterminate biliary strictures and ampullary tumors. Probe-based confocal laser endomicroscopy (pCLE) of the bile ducts is a difficult and expensive technique. Appropriate training needs to be established, since interpretation of images is challenging. pCLE can be an important diagnostic tool in the setting of indeterminate biliary strictures. PMID- 26147493 TI - Measuring disease levels in myeloma using flow cytometry in combination with other laboratory techniques: Lessons from the past 20 years at the Leeds Haematological Malignancy Diagnostic Service. AB - People with myeloma who obtain a good response to treatment have a better survival if sensitive molecular or flow-cytometric techniques show no detectable minimal residual disease (MRD). The application of MRD techniques to clinical trials is now considered to be increasingly important because treatment approaches are sufficiently effective that using survival outcomes is slowing down the identification of the best new treatments. The articles in this issue consider the laboratory requirements for harmonization of MRD analysis by flow cytometry but there are practical considerations that are also important in implementing a myeloma MRD assay in the cytometry laboratory. In particular, it is important to consider when to request, and how best to utilize, a bone marrow aspirate sample because the procedure is invasive and the cells obtained are valuable for a number of different investigations. This brief article considers some experience obtained over two decades of implementing a service for MRD detection, initially as a scientific bolt-on to clinical trials through to a routine clinical diagnostic assay. PMID- 26147494 TI - Role of glycine in nociceptive and non-nociceptive bladder reflexes and pudendal afferent inhibition of these reflexes in cats. AB - AIM: This study examined the role of glycinergic transmission in nociceptive and non-nociceptive bladder reflexes and in inhibition of these reflexes by pudendal nerve stimulation (PNS). METHODS: Cystometrograms (CMGs) were performed in alpha chloralose anesthetized cats by intravesical infusion of saline or 0.25% acetic acid (AA) to trigger, respectively, non-nociceptive or nociceptive bladder reflexes. PNS at 2 or 4 times threshold (T) intensity for inducing anal twitch was used to inhibit the bladder reflexes. Strychnine (a glycine receptor antagonist) was administered in cumulative doses (0.001-0.3 mg/kg, i.v.) at 60 120 min intervals. RESULTS: Strychnine at 0.001-0.3 mg/kg significantly (P < 0.05) increased bladder capacity and reduced contraction amplitude during saline CMGs but did not change these parameters during AA CMGs except at the 0.3 mg/kg dose which increased bladder capacity. Strychnine did not alter PNS inhibition during saline CMGs except at the highest dose at 2T intensity, but significantly (P < 0.05) suppressed PNS inhibition during AA CMGs after 0.001-0.003 mg/kg doses at 2T and 4T intensities. During AA CMGs strychnine (0.3 mg/kg) also unmasked a post-PNS excitatory effect that significantly reduced bladder capacity after termination of PNS. CONCLUSIONS: Glycinergic inhibitory neurotransmission in the central nervous system plays an unexpected role to tonically enhance the magnitude and reduce the bladder volume threshold for triggering the non nociceptive bladder reflex. This is attributable to inhibition by glycine of another inhibitory mechanism. Glycine also has a minor role in PNS inhibition of the nociceptive bladder reflex. Neurourol. Urodynam. 35:798-804, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26147496 TI - Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients. AB - PURPOSE: Symptomatic radiation pneumonitis (SRP), which decreases quality of life (QoL), is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4-12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT) to find the risk factors, which may have important effects on the risk of radiation induced complications. METHODS: In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO) technique. RESULTS: Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20), energy, age, body mass index (BMI) and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation. CONCLUSIONS: We suggest to define a dose volume percentage constraint of IV20< 37% (or AIV20< 310cc) for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung volume that received more than 20 Gy (cc). PMID- 26147495 TI - Lifestyle Factors in Cancer Survivorship: Where We Are and Where We Are Headed. AB - Advances in early detection and curative therapies have led to an increased number of cancer survivors over the last twenty years. With this population comes the need to evaluate the late and long term effects of cancer treatment and develop recommendations about how to optimally care for these survivors. Lifestyle factors (diet, body weight, physical activity, and smoking) have been linked to a higher risk of many medical comorbidities (cardiovascular, metabolic, etc.). There is increasing evidence linking these factors to the risk of developing cancer and likely cancer-related outcomes. This link has been studied extensively in common cancers like breast, colon, prostate, and lung cancers through observational studies and is now being prospectively evaluated in interventional studies. Realizing that survivors are highly motivated to improve their overall health after a diagnosis of cancer, healthy lifestyle recommendations from oncology providers can serve as a strong tool to motivate survivors to adopt health behavior changes. Our article aims to review the evidence that links lifestyle factors to cancer outcomes and provides clinical recommendations for cancer survivors. PMID- 26147497 TI - Spatiotemporal relationships between the cell shape and the actomyosin cortex of periodically protruding cells. AB - We investigate the dynamics of cell shape and analyze the actin and myosin distributions of cells exhibiting cortical density traveling waves. These waves propagate by repeated cycles of cortical compression (folding) and dilation (unfolding) that lead to periodic protrusions (oscillations) of the cell boundary. The focus of our detailed analysis is the remarkable periodicity of this phenotype, in which both the overall shape transformation and distribution of actomyosin density are repeated from cycle to cycle even though the characteristics of the shape transformation vary significantly for different regions of the cell. We show, using correlation analysis, that during traveling wave propagation cortical actin and plasma membrane densities are tightly coupled at each point along the cell periphery. We also demonstrate that the major protrusion appears at the wave trailing edge just after the actin cortex density has reached a maximum. Making use of the extraordinary periodicity, we employ latrunculin to demonstrate that sequestering actin monomers can have two distinct effects: low latrunculin concentrations can trigger and enhance traveling waves but higher concentrations of this drug retard the waves. The fundamental mechanism underlying this periodically protruding phenotype, involving folding and unfolding of the cortex-membrane couple, is likely to hold important clues for diverse phenomena including cell division and amoeboid-type migration. PMID- 26147498 TI - Unravelling the one-carbon metabolism of the acetogen Sporomusa strain An4 by genome and proteome analysis. AB - The Sporomusa genus comprises anaerobic spore-forming acetogenic bacteria that stain Gram-negative. Sporomusa species typically grow with one-carbon substrates and N-methylated compounds. In the degradation of these compounds methyltransferases are involved. In addition, Sporomusa species can grow autotrophically with H2 and CO2 , and use a variety of sugars for acetogenic growth. Here we describe a genome analysis of Sporomusa strain An4 and a proteome analysis of cells grown under five different conditions. Comparison of the genomes of Sporomusa strain An4 and Sporomusa ovata strain H1 indicated that An4 is a S. ovata strain. Proteome analysis showed a high abundance of several methyltransferases, predominantly trimethylamine methyltransferases, during growth with betaine, whereas trimethylamine is one of the main end-products of betaine degradation. In methanol degradation methyltransferases are also involved. In methanol-utilizing methanogens, two methyltransferases catalyse methanol conversion, methyltransferase 1 composed of subunits MtaB and MtaC and methyltransferase 2, also called MtaA. The two methyltransferase 1 subunits MtaB and MtaC were highly abundant when strain An4 was grown with methanol. However, instead of MtaA a methyltetrahydrofolate methyltransferase was synthesized. We propose a novel methanol degradation pathway in Sporomusa strain An4 that uses a methyltetrahydrofolate methyltransferase instead of MtaA. PMID- 26147499 TI - Pseudo-Interphase of Liposome Promotes 1,3-Dipolar Cycloaddition Reaction of Benzonitrile Oxide and N-Ethylmaleimide in Aqueous Solution. AB - The hydrophobic interior of a liposome membrane was used as a platform for the organic synthesis of hydrophobic compounds in water. The 1,3-dipolar cycloaddition of benzonitrile oxide (BNO) and N-ethylmaleimide (EMI) in liposome suspensions was carried out, and an increase in the reaction rate constant was observed depending on the liposome characteristics. While the reaction rate constant in 1,4-dioxane was 1.5 times higher than that in water, the reaction rate constant in an aqueous solution of cationic 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) liposome was 3 times higher than in water. The amount of substrate, BNO, accumulated in the DOTAP liposome was higher than that in 1,2 dipalmitoyl-3-trimethylammonium-propane (DPTAP), indicating that BNO prefers to be distributed in the liposome membrane in the liquid-disordered phase. The membrane polarity, GP340, as monitored by Laurdan, varied with the presence of BNO, while EMI slightly affected the membrane properties of the liposomes. These results suggest that the pseudo-interphase afforded by the liposome membrane can promote the 1,3-dipolar cycloaddition between BNO and EMI in water. PMID- 26147500 TI - Quantifying International Travel Flows Using Flickr. AB - Online social media platforms are opening up new opportunities to analyse human behaviour on an unprecedented scale. In some cases, the fast, cheap measurements of human behaviour gained from these platforms may offer an alternative to gathering such measurements using traditional, time consuming and expensive surveys. Here, we use geotagged photographs uploaded to the photo-sharing website Flickr to quantify international travel flows, by extracting the location of users and inferring trajectories to track their movement across time. We find that Flickr based estimates of the number of visitors to the United Kingdom significantly correlate with the official estimates released by the UK Office for National Statistics, for 28 countries for which official estimates are calculated. Our findings underline the potential for indicators of key aspects of human behaviour, such as mobility, to be generated from data attached to the vast volumes of photographs posted online. PMID- 26147501 TI - Gradual Rarefaction of Hematopoietic Precursors and Atrophy in a Depleted microRNA 29a, b and c Environment. AB - BACKGROUND: The self-renewing ability of HSCs is fundamental for the maintenance of a pool of bone marrow precursors throughout the life of an individual. The genetic mechanisms underlying such a complex process are still poorly understood. RESULTS AND SIGNIFICANCE: Here, we show that constitutive in vivo deletion of miR29ab1 leads to reduced number of HSCs and that miR29ab1 deficient bone marrow cannot repopulate the bone marrow of irradiated mice. An Affymetrix analysis of the miR29ab1 knockout mice identifies key proteins that could be responsible for this phenotype, as DNMT3a and b. Moreover, our findings reveal that whereas miR29b2c knockout mice do not exhibit any spontaneous abnormality, the double knock out--miR29ab1b2c--has marked generalized atrophy, raising the possibility that the two bi-cistrons might cooperate in order to maintain the stem cell number in general, not only limited to the bone marrow. PMID- 26147502 TI - Identification of an Immunogenic Mimic of a Conserved Epitope on the Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle (VLP) Peptide Display. AB - We have developed a peptide display platform based on VLPs of the RNA bacteriophage MS2 that combines the high immunogenicity of VLP display with affinity selection capabilities. Random peptides can be displayed on the VLP surface by genetically inserting sequences into a surface-exposed loop of the viral coat protein. VLP-displayed peptides can then be isolated by selection using antibodies, and the VLP selectants can then be used directly as immunogens. Here, we investigated the ability of this platform to identify mimotopes of a highly conserved conformational epitope present on the Plasmodium falciparum blood-stage protein AMA1. Using 4G2, a monoclonal antibody that binds to this epitope and is a potent inhibitor of erythrocyte invasion, we screened three different VLP-peptide libraries and identified specific VLPs that bound strongly to the selecting mAb. We then tested the ability of a handful of selected VLPs to elicit anti-AMA1 antibody responses in mice. Most of the selected VLPs failed to reliably elicit AMA1 specific antibodies. However, one VLP consistently induced antibodies that cross-reacted with AMA1. Surprisingly, this VLP bound to 4G2 more weakly than the other selectants we identified. Taken together, these data demonstrate that VLP-peptide display can identify immunogenic mimics of a complex conformational epitope and illustrate the promise and challenges of this approach. PMID- 26147503 TI - The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS). AB - INTRODUCTION: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a common, severe condition affecting 0.2 to 0.4 per cent of the population. Even so, no recent international EQ-5D based health-related quality of life (HRQoL) estimates exist for ME/CFS patients. The main purpose of this study was to estimate HRQoL scores using the EQ-5D-3L with Danish time trade-off tariffs. Secondary, the aims were to explore whether the results are not influenced by other conditions using regression, to compare the estimates to 20 other conditions and finally to present ME/CFS patient characteristics for use in clinical practice. MATERIAL AND METHODS: All members of the Danish ME/CFS Patient Association in 2013 (n=319) were asked to fill out a questionnaire including the EQ-5D-3L. From these, 105 ME/CFS patients were identified and gave valid responses. Unadjusted EQ-5D-3L means were calculated and compared to the population mean as well as to the mean of 20 other conditions. Furthermore, adjusted estimates were calculated using ordinary least squares (OLS) regression, adjusting for gender, age, education, and co-morbidity of 18 self-reported conditions. Data from the North Denmark Health Profile 2010 was used as population reference in the regression analysis (n=23,392). RESULTS: The unadjusted EQ-5D-3L mean of ME/CFS was 0.47 [0.41-0.53] compared to a population mean of 0.85 [0.84-0.86]. The OLS regression estimated a disutility of -0.29 [ 0.21;-0.34] for ME/CFS patients in this study. The characteristics of ME/CFS patients are different from the population with respect to gender, relationship, employment etc. CONCLUSION: The EQ-5D-3L-based HRQoL of ME/CFS is significantly lower than the population mean and the lowest of all the compared conditions. The adjusted analysis confirms that poor HRQoL of ME/CFS is distinctly different from and not a proxy of the other included conditions. However, further studies are needed to exclude the possible selection bias of the current study. PMID- 26147504 TI - Substantial Neuroprotective and Neurite Outgrowth-Promoting Activities by Bis(propyl)-cognitin via the Activation of Alpha7-nAChR, a Promising Anti Alzheimer's Dimer. AB - The cause of Alzheimer's disease (AD) could be ascribed to the progressive loss of functional neurons in the brain, and hence, agents with neuroprotection and neurite outgrowth-promoting activities that allow for the replacement of lost neurons may have significant therapeutic value. In the current study, the neuroprotective and the neurite outgrowth-promoting activities and molecular mechanisms of bis(propyl)-cognitin (B3C), a multifunctional anti-AD dimer, were investigated. Briefly, B3C (24 h pretreatment) fully protected against glutamate induced neuronal death in primary cerebellar granule neurons with an IC50 value of 0.08 MUM. The neuroprotection of B3C could be abrogated by methyllycaconitine, a specific antagonist of alpha7-nicotinic acetylcholine receptor (alpha7-nAChR). In addition, B3C significantly promoted neurite outgrowth in both PC12 cells and primary cortical neurons, as evidenced by the increase in the percentage of cells with extended neurites as well as the up-regulation of neuronal markers growth associated protein-43 and beta-III-tubulin. Furthermore, B3C rapidly upregulated the phosphorylation of extracellular signal-regulated kinase (ERK), a critical signaling molecule in neurite outgrowth that is downstream of the alpha7-nAChR signal pathway. Specific inhibitors of ERK and alpha7-nAChR, but not those of p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase, blocked the neurite outgrowth as well as ERK activation in PC12 cells induced by B3C. Most importantly, genetic depletion of alpha7-nAChR significantly abolished B3C induced neurite outgrowth in PC12 cells. Taken together, our results suggest that B3C provided neuroprotection and neurite outgrowth-promoting activities through the activation of alpha7-nAChR, which offers a novel molecular insight into the potential application of B3C in AD treatment. PMID- 26147505 TI - Graft rinse prior to reperfusion in liver transplantation: literature review and online survey within the Eurotransplant community. AB - Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty-four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community. PMID- 26147506 TI - Experimental and Theoretical Investigation of Crystallographic Orientation Dependence of Nanoscratching of Single Crystalline Copper. AB - In the present work, we perform experiments and molecular dynamics simulations to elucidate the underlying deformation mechanisms of single crystalline copper under the load-controlled multi-passes nanoscratching using a triangular pyramidal probe. The correlation of microscopic deformation behavior of the material with macroscopically-observed machining results is revealed. Moreover, the influence of crystallographic orientation on the nanoscratching of single crystalline copper is examined. Our simulation results indicate that the plastic deformation of single crystalline Cu under the nanoscratching is exclusively governed by dislocation mechanisms. However, there is no glissile dislocation structure formed due to the probe oscillation under the load-controlled mode. Both experiments and MD simulations demonstrate that the machined surface morphologies in terms of groove depth and surface pile-up exhibit strong crystallographic orientation dependence, because of different geometries of activated slip planes cutting with free surfaces and strain hardening abilities associated with different crystallographic orientations. PMID- 26147508 TI - A Computational Framework for Bioimaging Simulation. AB - Using bioimaging technology, biologists have attempted to identify and document analytical interpretations that underlie biological phenomena in biological cells. Theoretical biology aims at distilling those interpretations into knowledge in the mathematical form of biochemical reaction networks and understanding how higher level functions emerge from the combined action of biomolecules. However, there still remain formidable challenges in bridging the gap between bioimaging and mathematical modeling. Generally, measurements using fluorescence microscopy systems are influenced by systematic effects that arise from stochastic nature of biological cells, the imaging apparatus, and optical physics. Such systematic effects are always present in all bioimaging systems and hinder quantitative comparison between the cell model and bioimages. Computational tools for such a comparison are still unavailable. Thus, in this work, we present a computational framework for handling the parameters of the cell models and the optical physics governing bioimaging systems. Simulation using this framework can generate digital images of cell simulation results after accounting for the systematic effects. We then demonstrate that such a framework enables comparison at the level of photon-counting units. PMID- 26147507 TI - Evaluation of MCF10A as a Reliable Model for Normal Human Mammary Epithelial Cells. AB - Breast cancer is the most common cancer in women and a leading cause of cancer related deaths for women worldwide. Various cell models have been developed to study breast cancer tumorigenesis, metastasis, and drug sensitivity. The MCF10A human mammary epithelial cell line is a widely used in vitro model for studying normal breast cell function and transformation. However, there is limited knowledge about whether MCF10A cells reliably represent normal human mammary cells. MCF10A cells were grown in monolayer, suspension (mammosphere culture), three-dimensional (3D) "on-top" Matrigel, 3D "cell-embedded" Matrigel, or mixed Matrigel/collagen I gel. Suspension culture was performed with the MammoCult medium and low-attachment culture plates. Cells grown in 3D culture were fixed and subjected to either immunofluorescence staining or embedding and sectioning followed by immunohistochemistry and immunofluorescence staining. Cells or slides were stained for protein markers commonly used to identify mammary progenitor and epithelial cells. MCF10A cells expressed markers representing luminal, basal, and progenitor phenotypes in two-dimensional (2D) culture. When grown in suspension culture, MCF10A cells showed low mammosphere-forming ability. Cells in mammospheres and 3D culture expressed both luminal and basal markers. Surprisingly, the acinar structure formed by MCF10A cells in 3D culture was positive for both basal markers and the milk proteins beta-casein and alpha lactalbumin. MCF10A cells exhibit a unique differentiated phenotype in 3D culture which may not exist or be rare in normal human breast tissue. Our results raise a question as to whether the commonly used MCF10A cell line is a suitable model for human mammary cell studies. PMID- 26147509 TI - Recombinant HBV vaccine enhances the rate of sustained virological response when early initiated after anti-HCV combination therapy. AB - The overall SVR rate for chronic hepatitis C genotype 4 using the Standard of care is 54.3%. HBV infection can be prevented by the administration of effective and safe vaccine. Evaluation of the vaccination-induced anti-HBs response rates in a cohort of HCV Egyptian patients after being exposed to antiviral combination therapy and the magnitude of its effect on the rate of SVR through its putative role in induction of crossed immunity. (A) 500 HCV patients who had completed the course of antiviral therapy and achieved ETR were retrospectively analyzed and received 20 MUg of recombinant DNA vaccine for hepatitis B at time intervals (0, 1, and 4 months). The first dose of the vaccine was initiated one month post treatment. (B) Laboratory analysis: Included routine preliminary investigations to anti viral therapy and specific investigations as determination of anti-HBs antibodies 2 months following the third dose of vaccine. 433 patients showed protective response (86.6%), 67 patients were non-responders (13.4%) (P = 0.003). Adding HBV vaccine 1 month post-treatment increased SVR (400 patients, 80%) (chi(2) = 40.3, P = 0.000). Diabetes affect response to HBV vaccine (P = 0.0001). Adding HBV vaccine to the post treatment care of patients with HCV after termination of antiviral therapy gain two benefits; protection from HBV and significant increase in rates of SVR. PMID- 26147510 TI - Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis. AB - Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs. PMID- 26147512 TI - Effects of glyceryl polyethylene glycol ricinoleate on nutrient utilisation and performance of broiler chickens. AB - A completely randomised design study with a 2 * 2 factorial arrangement was conducted to observe effects of an emulsifier (glyceryl polyethylene glycol ricinoleate (GPR)) on nutrient utilisation and performance of broiler chickens. A total of 384 male broiler chickens were used to determine the influence of GPR (without addition or added at 0.04% of diet) and two levels of apparent metabolisable energy (AMEN) (according to standard requirements (Diets SE) or energy reduced by 0.4 MJ/kg diet (Diets LE)) on birds' performance and apparent total tract digestibility (ATTD). ATTD of ether extract (EE) and AMEN were measured on d 14 and 35, and ATTD of neutral detergent fibre (NDF) was measured on d 35. All diets were based on wheat-maize-soybean meal with rapeseed oil and lard (blend of 50:50) as fat sources. During the grower period and the whole trial, birds fed Diets supplemented with GPR were characterised by higher body weight gain (BWG) and lower feed conversion ratio (FCR) compared to chicken receiving diets without GPR (p < 0.05). At the end of experiment, birds fed Diet LE without GPR were characterised by lower BWG and higher FCR (p < 0.05). Supplementation with GPR caused a higher ATTD of EE for diets SE and LE at d 14 and 35 (p < 0.05). Moreover, the GPR addition to Diet LE improved ATTD of NDF at d 35 (p < 0.05). In conclusion, the findings suggest that GPR effects the digestion of a blend of animal fat/rapeseed oil positively, even in a practical maize-wheat-based broiler diet with decreased AMEN level. PMID- 26147513 TI - Anti-cholelithogenic potential of dietary spices and their bioactives. AB - Dietary hypocholesterolemic spices-curcumin (active compound of turmeric (Curcuma longa)) and capsaicin (active compound of red pepper (Capsicum annuum)), the active principles of spices-turmeric (Curcuma longa) and red pepper (Capsicum annuum), fenugreek (Trigonella foenum-graecum) seeds, garlic (Allium sativum), and onion (Allium cepa) are documented to have anti-cholelithogenic property in animal model. These spices prevent the induction of cholesterol gallstones by lithogenic high cholesterol diet and also regress the pre-established cholesterol gallstones, by virtue of their hypolipidemic potential. The antilithogenic influence of these spices is primarily attributable to their hypocholesterolemic effect. Increased cholesterol saturation index, cholesterol:phospholipid ratio and cholesterol:bile acid ratio in the bile caused by the lithogenic diet was countered by these spices. The antilithogenicity of these hypocholesterolemic spices was considered to be due also to their influence on biliary proteins that have pro-nucleating activity and anti-nucleating activity. Investigations on the involvement of biliary proteins in cholesterol crystal nucleation revealed that in an in vitro bile model, low molecular weight biliary proteins of the lithogenic diet fed animals have a pro-nucleating activity. On the contrary, low molecular weight biliary proteins of the animals fed hypocholesterolemic spices along with lithogenic diet showed a potent anti-nucleating activity. PMID- 26147511 TI - The C825T Polymorphism of the G-Protein beta3 Gene as a Risk Factor for Depression: A Meta-Analysis. AB - BACKGROUND: TheG-protein beta3 gene (GNbeta3) has been implicated in psychiatric illness through its effects upon intracellular transduction of several neurotransmitter receptors. Multiple studies have investigated the relationship of the C825T polymorphism of the GNbeta3 gene (GNbeta3 C825T) to depression and antidepressant response. However, the relationship between GNbeta3 C825T and depression remains inconsistent. Therefore, here we performed a meta-analysis to investigate the role of GNbeta3 C825Tin depression risk. METHODS: Published case control studies examining the association between GNbeta3 C825T and depression were systematically searched for through several electronic databases (PubMed, Scopus, Science Direct, Springer, Embase, psyINFO, and CNKI). The association between GNbeta3 C825T and depression risk were assessed by odd ratios (ORs) and their 95% confidence intervals (CIs) for each study. Pooled ORs were constructed for allele contrast (C versus T), homozygote (CC versus TT) model, heterozygote (CC versus CT) model, dominant model (CC + CT versus TT), and recessive (CC versus TT+CT) model. In order to evaluate possible biases, a sensitivity analysis was conducted by sequential deletion of individual studies in an attempt to assess the contribution of each individual dataset to the pooled OR. RESULTS: Nine studies, including 1055 depressed patients and 1325 healthy controls, were included. A significant association between GNbeta3 C825Tand depression was found to exist, suggesting that the T-allele of GNbeta3 C825Tcan increase susceptibility to depression. After stratification by ethnicity, the same association was found in the Asian subpopulation, but not the Caucasian subpopulation. CONCLUSIONS: This is the first meta-analysis to reveal a relationship between GNbeta3 C825T and depression. Asian T-allele carriers of GNbeta3 C825T appear to be more susceptible to depression. PMID- 26147514 TI - Visualizing the relevance of bacterial blue- and red-light receptors during plant pathogen interaction. AB - The foliar pathogen Pseudomonas syringae pv. tomato DC3000 (Pst) leads to consistent losses in tomato crops, urging to multiply investigations on the physiological bases for its infectiveness. As other P. syringae pathovars, Pst is equipped with photoreceptors for blue and red light, mimicking the photosensing ability of host plants. In this work we have investigated Pst strains lacking the genes for a blue-light sensing protein (PstLOV), for a bacteriophytochrome (PstBph1) or for heme-oxygenase-1. When grown in culturing medium, all deletion mutants presented a larger growth than wild-type (WT) Pst under all other light conditions, with the exception of blue light which, under our experimental conditions (photon fluence rate = 40 MUmol m(-2) s(-1)), completely suppressed the growth of the deletion mutants. Each of the knockout mutants shows stronger virulence towards Arabidopsis thaliana than PstWT, as evidenced by macroscopic damages in the host tissues of infected leaves. Mutated bacteria were also identified in districts distant from the infection site using scanning electron microscopy. These results underscore the importance of Pst photoreceptors in responding to environmental light inputs and the partial protective role that they exert towards host plants during infection, diminishing virulence and invasiveness. PMID- 26147515 TI - Susceptibility of Helicobacter pylori to antibiotics in Chinese patients. AB - OBJECTIVE: Antibiotic resistance to Helicobacter pylori (H. pylori) has been increasing worldwide. The study aimed to evaluate in vitro susceptibility and resistance patterns to antibiotics in empirical H. pylori eradication regimens, and to determine the optimal antibiotics for treatment. METHODS: H. pylori strains (n =181) were obtained from gastric biopsies of patients with upper gastrointestinal symptoms who underwent esophagogastroduodenoscopy from March to December 2013. The susceptibility of H. pylori strains to amoxicillin (AMX), metronidazole (MTZ), clarithromycin (CLR), amoxicillin-clavulanate (AMC), cephalothin (CEP), cefuroxime (CXM), cefixime (CFM), moxifloxacin (MFX) and minocycline (MNO) was determined. RESULTS: Dual resistance to MTZ + CLR was detected in 48 (26.5%) isolates, MTZ + MFX in 94 (51.9%), and CLR + MFX in 49 (27.1%). Overall, 41 (22.7%) were resistant to MTZ + CLR + MFX. MTZ and CLR resistance rates were significantly associated with the history of H. pylori eradication but there was no significant difference in MFX resistance rates between treated and untreated patients (P = 0.674). No significant relationship was found between antibiotic resistance and patient's gender, age, endoscopic findings, inflammatory severity or gastric atrophy. CONCLUSIONS: AMX, AMC, MNO and cephalosporins, but not MTZ, CLR and MFX, showed good in vitro anti-H. pylori activity. Among cephalosporins, CXM was the most active. H. pylori resistance is higher in patients with previous H. pylori eradication. PMID- 26147516 TI - Secondary growth among former prisoners of war's adult children: The result of exposure to stress, secondary traumatization, or personality traits? AB - The long-term toll of war captivity on secondary traumatization (ST) on adult children has recently been exemplified. Several studies have also revealed that indirect exposure to trauma might be accompanied by positive psychological changes. This study examined secondary posttraumatic growth (SG) among adult children of former prisoners of war (ex-POWs' children) who were compared with adult children of comparable veterans (controls' children). Furthermore, we examined the role of five-factor personality traits in the associations between exposure to stress stemming from fathers' behaviors, ST symptoms, and SG. Participants were Israeli ex-POWs' children (N = 98) and controls' children (N = 90), whose fathers fought in the 1973 Yom Kippur War. Results show that ex-POWs' children reported higher levels of SG compared with controls' children. ST symptoms were found to mediate the association between research group and SG, and the direct effect was found to be conditioned at the levels of participants' extroversion. Furthermore, among ex-POWs' children, extroversion and openness to the experience personality traits, as well as exposure to stress, were found to predict SG. Forty years after the war ended, the experience of living with ex POWs is associated with ex-POWs' children SG that might be more related to their exposure to stress and personality traits than their ST symptoms. Clinical interventions aiming to increase the levels of SG among indirect victims of captivity should consider the influence of pretrauma resources, trauma characteristics, and posttrauma factors. (PsycINFO Database Record PMID- 26147518 TI - The protective function of personal growth initiative among a genocide-affected population in Rwanda. AB - The aim of the current study was to investigate the extent to which individual differences in personal growth initiative (PGI) were associated with lower reports of functional impairment of daily activities among a genocide-affected population in Rwanda. PGI measures an individual's motivation to develop as a person and the extent to which he or she is active in setting goals that work toward achieving self-improvement. We found that PGI was negatively associated with functional impairment when controlling for depression, posttraumatic stress disorder, and other demographic factors. Our results suggest that PGI may constitute an important mindset for facilitating adaptive functioning in the aftermath of adversity and in the midst of psychological distress, and as such they might have practical applications for the development of intervention programs. PMID- 26147517 TI - The relation between insecure attachment and posttraumatic stress: Early life versus adulthood traumas. AB - The present study examined the relations between insecure attachment and posttraumatic stress disorder (PTSD) symptoms among community-dwelling older adults with exposure to a broad range of traumatic events. Attachment anxiety and attachment avoidance predicted more severe symptoms of PTSD and explained unique variance in symptom severity when compared to other individual difference measures associated with an elevated risk of PTSD, including NEO neuroticism and event centrality. A significant interaction between the developmental timing of the trauma and attachment anxiety revealed that the relation between PTSD symptoms and attachment anxiety was stronger for individuals with current PTSD symptoms associated with early life traumas compared to individuals with PTSD symptoms linked to adulthood traumas. Analyses examining factors that account for the relation between insecure attachment and PTSD symptoms indicated that individuals with greater attachment anxiety reported stronger physical reactions to memories of their trauma and more frequent voluntary and involuntary rehearsal of their trauma memories. These phenomenological properties of trauma memories were in turn associated with greater PTSD symptom severity. Among older adults with early life traumas, only the frequency of involuntary recall partially accounted for the relation between attachment anxiety and PTSD symptoms. Our differential findings concerning early life versus adulthood trauma suggest that factors underlying the relation between attachment anxiety and PTSD symptoms vary according to the developmental timing of the traumatic exposure. Overall our results are consistent with attachment theory and with theoretical models of PTSD according to which PTSD symptoms are promoted by phenomenological properties of trauma memories. PMID- 26147519 TI - Abuse in childhood and psychopathic traits in a sample of violent offenders. AB - A significant body of research underlines the link between the exposure to abuse in childhood and subsequent criminal behaviors. Research on the role played by childhood interpersonal trauma in the development of psychopathy, however, is still scant. The aim of this study was to explore the relationship between childhood experiences of abuse and psychopathic traits in a group of violent offenders from Italy. Seventy-eight inmates who were convicted of violent crimes participated in this study. Participants were administered the Traumatic Experience Checklist to assess childhood experiences of emotional, physical, and sexual abuse, and the Hare Psychopathy Checklist-Revised (PCL-R) to assess psychopathic traits. Almost two thirds of the participants reported either emotional, physical, or sexual abuse in childhood, with 17% having experienced all 3 types of abuse investigated in this study. Emotional abuse resulted in a positive predictor of PCL-R total scores and its Interpersonal-Affective and Lifestyle-Antisocial factors. This suggests that emotional abuse in childhood, in combination with neurobiological and temperamental vulnerabilities, can foster the development of psychopathic traits. PMID- 26147520 TI - Differentiating between appraisal process and product in cognitive theories of posttraumatic stress. AB - Biased appraisal is central to cognitive theories of posttraumatic stress, but little research has examined the potentially distinct meanings of the term. The ongoing process of appraising social information and the beliefs that emerge as products of that process can be distinguished conceptually. This study sought to examine whether these 2 meanings are empirically distinct as well, and if so, to begin exploring potential relations between these appraisal constructs and posttraumatic stress symptoms. Soldiers (N = 424) preparing for deployment to Iraq or Afghanistan were administered measures of each construct. Results of confirmatory factor analysis suggest that the appraisal process and the products of that process (i.e., beliefs) are indeed distinct. Structural equation models are consistent with cognitive bias and social information processing literatures, which posit that a biased appraisal process may contribute to the development of dysfunctional beliefs and posttraumatic stress symptoms following trauma. The potential utility of distinctly conceptualizing and measuring the appraisal process in both clinical and research settings is discussed. PMID- 26147521 TI - Cognitive-behavioral variables mediate the impact of violent loss on post-loss psychopathology. AB - Research has shown that violent losses lead to more severe emotional distress than do nonviolent losses. Little is known about the psychological mechanisms underlying the debilitating impact of violent loss. In the current study, the authors used self-reported data of 496 bereaved individuals, bereaved in the last 3 years, to examine the role of seven cognitive-behavioral variables in mediating the impact of violent loss: (a) a sense of "unrealness" about the irreversibility of the separation, negative cognitions about (b) the self, (c) life, (d) the future, and (e) catastrophic misinterpretations of grief-reactions, and indices of (f) anxious avoidance and (g) depressive avoidance behavior. Outcomes showed that people bereaved by violent losses (due to homicide, suicide, or accident) had significantly higher symptom-levels of Prolonged Grief Disorder (PGD), posttraumatic stress disorder (PTSD), and depression than persons bereaved by nonviolent losses. Indices of unrealness, negative cognitions about the self, the future, catastrophic misinterpretations, and depressive avoidance were all significant independent mediators of the linkages between violent loss and symptom-levels of PGD and depression. Negative cognitions about the future, catastrophic misinterpretations, and depressive and anxious avoidance emerged as unique mediators of the association between violent loss and elevated PTSD severity. Findings underscore that cognitive-behavioral variables are a critical component of elevated emotional distress following violent loss. PMID- 26147522 TI - Perceptions of the support that mothers and fathers of children with cochlear implants receive in South Australia: A qualitative study. AB - OBJECTIVE: The study explored the perceptions of parents of children with cochlear implants regarding the support they have received. DESIGN: Semi structured interviews were conducted and the resultant data was subjected to thematic analysis. STUDY SAMPLE: Participants were 12 mothers and four fathers from South Australia with a child with cochlear implants. RESULTS: Three major themes emerged: (1) a journey into a new world for parents, (2) services meet many but not all needs, and (3) parent connections and relationships. Most parents were satisfied with surgical, audiology, and early intervention services as well as specialist hearing-impairment schools, and perceived this support as helpful and adequate. However, some parents were critical of non-specialized teaching staff, and technical support for hearing devices. Parent recommendations for improved service provision included increased support, improved information, and additional professional services. CONCLUSIONS: Parent contributions suggest a need for service providers to develop support that is not only child-need oriented, but parent-need oriented, to better address service gaps. With a deeper understanding of parents' experiences and needs, service providers will have a greater capacity to develop a broader model of service that enhances parental engagement and coping. PMID- 26147523 TI - Echoes of a distant time: effects of historical processes on contemporary genetic patterns in Galaxias platei in Patagonia. AB - Interpreting the genetic structure of a metapopulation as the outcome of gene flow over a variety of timescales is essential for the proper understanding of how changes in landscape affect biological connectivity. Here we contrast historical and contemporary connectivity in two metapopulations of the freshwater fish Galaxias platei in northern and southernmost Patagonia where paleolakes existed during the Holocene and Pleistocene, respectively. Contemporary gene flow was mostly high and asymmetrical in the northern system while extremely reduced in the southernmost system. Historical migration patterns were high and symmetric in the northern system and high and largely asymmetric in the southern system. Both systems showed a moderate structure with a clear pattern of isolation by distance (IBD). Effective population sizes were smaller in populations with low contemporary gene flow. An approximate Bayesian computation (ABC) approach suggests a late Holocene colonization of the lakes in the northern system and recent divergence of the populations from refugial populations from east and west of the Andes. For the southern system, the ABC approach reveals that some of the extant G. platei populations most likely derive from an ancestral population inhabiting a large Pleistocene paleolake while the rest derive from a higher altitude lake. Our results suggest that neither historical nor contemporary processes individually fully explain the observed structure and geneflow patterns and both are necessary for a proper understanding of the factors that affect diversity and its distribution. Our study highlights the importance of a temporal perspective on connectivity to analyse the diversity of spatially complex metapopulations. PMID- 26147524 TI - The Murine Model of Mucopolysaccharidosis IIIB Develops Cardiopathies over Time Leading to Heart Failure. AB - Mucopolysaccharidosis (MPS) IIIB is a lysosomal disease due to the deficiency of the enzyme alpha-N-acetylglucosaminidase (NAGLU) required for heparan sulfate (HS) degradation. The disease is characterized by mild somatic features and severe neurological disorders. Very little is known on the cardiac dysfunctions in MPS IIIB. In this study, we used the murine model of MPS IIIB (NAGLU knockout mice, NAGLU(-/-)) in order to investigate the cardiac involvement in the disease. Echocardiographic analysis showed a marked increase in left ventricular (LV) mass, reduced cardiac function and valvular defects in NAGLU(-/-) mice as compared to wild-type (WT) littermates. The NAGLU(-/-) mice exhibited a significant increase in aortic and mitral annulus dimension with a progressive elongation and thickening of anterior mitral valve leaflet. A severe mitral regurgitation with reduction in mitral inflow E-wave-to-A-wave ratio was observed in 32-week-old NAGLU(-/-) mice. Compared to WT mice, NAGLU(-/-) mice exhibited a significantly lower survival with increased mortality observed in particular after 25 weeks of age. Histopathological analysis revealed a significant increase of myocardial fiber vacuolization, accumulation of HS in the myocardial vacuoles, recruitment of inflammatory cells and collagen deposition within the myocardium, and an increase of LV fibrosis in NAGLU(-/-) mice compared to WT mice. Biochemical analysis of heart samples from affected mice showed increased expression levels of cardiac failure hallmarks such as calcium/calmodulin dependent protein kinase II, connexin43, alpha-smooth muscle actin, alpha actinin, atrial and brain natriuretic peptides, and myosin heavy polypeptide 7. Furthermore, heart samples from NAGLU(-/-) mice showed enhanced expression of the lysosome-associated membrane protein-2 (LAMP2), and the autophagic markers Beclin1 and LC3 isoform II (LC3-II). Overall, our findings demonstrate that NAGLU(-/-) mice develop heart disease, valvular abnormalities and cardiac failure associated with an impaired lysosomal autophagic flux. PMID- 26147525 TI - Endothelial Snail Regulates Capillary Branching Morphogenesis via Vascular Endothelial Growth Factor Receptor 3 Expression. AB - Vascular branching morphogenesis is activated and maintained by several signaling pathways. Among them, vascular endothelial growth factor receptor 2 (VEGFR2) signaling is largely presented in arteries, and VEGFR3 signaling is in veins and capillaries. Recent reports have documented that Snail, a well-known epithelial to-mesenchymal transition protein, is expressed in endothelial cells, where it regulates sprouting angiogenesis and embryonic vascular development. Here, we identified Snail as a regulator of VEGFR3 expression during capillary branching morphogenesis. Snail was dramatically upregulated in sprouting vessels in the developing retinal vasculature, including the leading-edged vessels and vertical sprouting vessels for capillary extension toward the deep retina. Results from in vitro functional studies demonstrate that Snail expression colocalized with VEGFR3 and upregulated VEGFR3 mRNA by directly binding to the VEGFR3 promoter via cooperating with early growth response protein-1. Snail knockdown in postnatal mice attenuated the formation of the deep capillary plexus, not only by impairing vertical sprouting vessels but also by downregulating VEGFR3 expression. Collectively, these data suggest that the Snail-VEGFR3 axis controls capillary extension, especially in vessels expressing VEGFR2 at low levels. PMID- 26147527 TI - Muscle strength: clinical and prognostic value of hand-grip dynamometry. AB - PURPOSE OF REVIEW: Grip strength measured by dynamometry is well established as an indicator of muscle status, particularly among older adults. This review was undertaken to provide a synopsis of recent literature addressing the clinical and prognostic value of hand-grip dynamometry. RECENT FINDINGS: Numerous large-scale normative grip strength projects have been published lately. Other recent studies have reinforced the concurrent relationship of grip strength with measures of nutritional status or muscle mass and measures of function and health status. Studies published in the past few years have confirmed the value of grip strength as a predictor of mortality, hospital length of stay, and physical functioning. SUMMARY: As a whole, the recent literature supports the use of hand-grip dynamometry as a fundamental element of the physical examination of patients, particularly if they are older adults. PMID- 26147526 TI - Periconceptional Seafood Intake and Fetal Growth. AB - BACKGROUND: Previous reports of associations of maternal seafood intake with fetal growth were inconsistent. Further, little is known whether associations differ across seafood subtypes or fetal growth indices. METHODS: Among 3141 participants of the Omega study, a pregnancy cohort study, we investigated associations of periconceptional shell, lean, and fatty fish intake with fetal growth indices. We categorised food frequency questionnaire reported seafood intake into frequencies of: <0.2 servings/month, 0.2 servings/month -<0.5 servings/week, 0.5-1 servings/week, and >1 servings/week. We abstracted birthweight, birth length, and head circumference from medical records. Using generalised linear models with a log link, the Poisson family, and robust standard errors, we estimated relative risks and 95% confidence intervals (CI) for low birthweight (LBW, <2500 g) and linear regression models to estimate mean differences for continuous fetal growth indices across seafood intake categories. RESULTS: Medians (interquartile range) of shell, lean, and fatty fish intake were 0.3 (0-0.9), 0.5 (0-1.0), and 0.5 (0.1-1.0) servings/week, respectively. Lean fish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 2.2-fold higher risk of LBW (95% CI 1.2, 4.1). Shellfish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 0.6 kg/m(3) higher mean ponderal index (95% CI 0.0, 1.2 kg/m(3) ). There was no evidence for associations of total seafood or seafood subtype intake with other fetal growth indices. CONCLUSIONS: Higher intakes of lean fish and shellfish were associated with a higher risk of LBW and higher mean ponderal index, respectively. Findings highlight the importance of considerations of seafood subtype in similar investigations. PMID- 26147528 TI - Noncoeliac gluten sensitivity: a diagnostic dilemma. AB - PURPOSE OF REVIEW: Noncoeliac gluten sensitivity (NCGS) has gained attention as an emerging clinical entity. Data regarding the epidemiology, pathogenesis, and management of NCGS are scattered in view of the diagnostic uncertainty surrounding the disorder. We aim to provide a current perspective of NCGS and its associated controversies. RECENT FINDINGS: NCGS consists of a spectrum of intestinal and extraintestinal symptoms related to the ingestion of gluten containing food, yet in the absence of coeliac disease or wheat allergy. To date, no specific biomarker exists for NCGS, thereby leaving the diagnosis to be confirmed by dietary elimination followed by double-blind placebo-controlled gluten-based rechallenges. Unfortunately, this technique is cumbersome, not readily-available in routine clinical practise, and can still leave the diagnosis of NCGS open to debate as to whether the effects demonstrated can be specifically attributed to the gluten-protein per se or rather coexisting nongluten components, such as fermentable carbohydrates and amylase-trypsin inhibitors. SUMMARY: Physicians are increasingly being posed with the dilemma of patients presenting with self-reported NCGS. However, this appears to be the tip of the iceberg and future studies are in need of delineating which gluten-based component is responsible for each individual patient's complaint. PMID- 26147529 TI - Serum metabolomics in animal models and human disease. AB - PURPOSE OF REVIEW: The aim of this study is to highlight some recent uses of serum metabolomics in human and animal studies. The main themes are the importance of understanding the underlying variation in human metabolism and the use of serum metabolomics in disease profiling. RECENT FINDINGS: Several studies have attempted to use serum metabolomics to develop noninvasive biomarkers of disease and/or track the consequences of nutritional and genetic interventions. Many advances have been made with common changes being identified in ageing, the menopause and cancer but several problems of interpretation have emerged from these studies. These include the small sample sizes in most human studies and the differences between human and rodent metabolomes. However, a metabolic screen of over 1000 'healthy' humans (the Humsermet project) has highlighted many variables that may be used to refine the interpretation and design of previous and future human studies alike, in addition to data mining. SUMMARY: Some common serum metabolome alterations have been identified but many inconsistencies remain. The construction of a human serum metabolome database should be informative in the design of future human and animal model studies. PMID- 26147530 TI - Intramuscular water movement during and after isometric muscle contraction: evaluation at different exercise intensities. AB - We aimed at evaluating the effect of isometric muscle contraction on intramuscular water movement at different exercise intensities. Seven men performed 1-min isometric ankle dorsiflexion (20% and 50% maximal voluntary contractions [MVCs]) with a non-magnetic custom-made dynamometer, inside a magnetic resonance (MR) device. Axial diffusion-weighted images were obtained before, during and at 1-20 min (1-min interval) after the exercise to calculate the apparent diffusion coefficient (ADC) of the tibialis anterior. Under the same exercise condition, the concentration change of total haemoglobin (Hb) and myoglobin (Mb) (total Hb/Mb) within the tibialis anterior was assessed by performing near-infrared spectroscopy before, during and after the exercise outside the MR device. The 20% MVC exercise significantly increased the ADC only at 1 min postexercise (P<0.01), whereas the ADC significantly increased during and at 2-20 min after the 50% MVC exercise (P<0.01). The 20% MVC exercise decreased the total Hb/Mb during exercise (P<0.01), but the value significantly increased at 1 min postexercise (P<0.01). The total Hb/Mb significantly decreased during the 50% MVC exercise, but significantly increased at 1-5 min postexercise (P<0.01). One-minute moderate-intensity isometric exercise activates intramuscular water movement during and after the exercise. This activation was found even after a low-intensity exercise, but the effect was small and did not last long. The effect of intramuscular hyperaemia on the postexercise ADC elevation may be limited to the very early period after low- to moderate intensity exercises. PMID- 26147531 TI - Covered Stent Membrane Design for Treatment of Atheroembolic Disease at Carotid Artery Bifurcation and Prevention of Thromboembolic Stroke: An In Vitro Experimental Study. AB - In this study, a polymeric membrane has been designed and developed for carotid stents to prevent detachment of emboli from the arterial wall and subsequent stroke, while maintaining side-branch flow. Prototypes of different geometrical design parameters have been fabricated and their performance has been evaluated in vitro under physiological pulsatile flow condition in a life-size silicone anastomotic model of carotid artery bifurcation. These evaluations include both quantitative and qualitative experimental (in vitro) assessments of emboli prevention capability, side-branch flow preservation, and flow visualization. The covered stents with the novel membrane demonstrated significantly higher emboli prevention capability than the corresponding bare nitinol stent as well as some earlier related designs, while preserving more than 93% of the original flow of the external carotid artery (ECA). Flow in the ECA through these covered stents was uniform without evidence of undesirable flow recirculation or retrograde flow that might predispose the vessel wall to intimal thickening and atherosclerotic plaque formation. This study demonstrated the potential of these novel covered stent designs for the treatment of carotid atherosclerotic stenosis and prevention of late embolic stroke. However, further in vivo investigations of biological effects and mechanical performance of this covered stent design (e.g., its thrombogenicity potential and biocompatibility) are warranted. PMID- 26147532 TI - Retrosplenial cortex maps the conjunction of internal and external spaces. AB - Intelligent behavior demands not only multiple forms of spatial representation, but also coordination among the brain regions mediating those representations. Retrosplenial cortex is densely interconnected with the majority of cortical and subcortical brain structures that register an animal's position in multiple internal and external spatial frames of reference. This unique anatomy suggests that it functions to integrate distinct forms of spatial information and provides an interface for transformations between them. Evidence for this was found in rats traversing two different routes placed at different environmental locations. Retrosplenial ensembles robustly encoded conjunctions of progress through the current route, position in the larger environment and the left versus right turning behavior of the animal. Thus, the retrosplenial cortex has the requisite dynamics to serve as an intermediary between brain regions generating different forms of spatial mapping, a result that is consistent with navigational and episodic memory impairments following damage to this region in humans. PMID- 26147534 TI - Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis. AB - Individuals with TRPC6 mutations have variable phenotypes, ranging from healthy carrier to focal segmental glomerulosclerosis (FSGS) leading to renal failure. Here, we describe a family where six members had a novel TRPC6 p.R68W (c.202C>T) mutation, two of whom had renal failure from FSGS, and one had proteinuria. One healthy carrier donated a kidney to her sister. Both donor and recipient had no proteinuria at 20 years posttransplant. Two synonymous NPHS1 polymorphisms, rs2285450 (c.294C>T) and rs437168 (c.2289C>T) segregated with renal failure in this family. These variants had higher allele frequencies in 97 unrelated patients with nephrotic syndrome or FSGS compared to 224 controls. Using patch clamp experiments in HEK293 and podocytes, we showed that the p.R68W mutation increased TRPC6 current amplitudes, which may be explained by enhanced TRPC6 surface expression. Additionally, while wild-type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism. When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft. PMID- 26147533 TI - Identification of a Vav2-dependent mechanism for GDNF/Ret control of mesolimbic DAT trafficking. AB - Dopamine (DA) homeostasis is essential for a variety of brain activities. Dopamine transporter (DAT)-mediated DA reuptake is one of the most critical mechanisms for normal DA homeostasis. However, the molecular mechanisms underlying the regulation of DAT activity in the brain remain poorly understood. Here we show that the Rho-family guanine nucleotide exchange factor protein Vav2 is required for DAT cell surface expression and transporter activity modulated by glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor Ret. Mice deficient in either Vav2 or Ret displayed elevated DAT activity, which was accompanied by an increase in intracellular DA selectively in the nucleus accumbens. Vav2(-/-) mice exposed to cocaine showed reduced DAT activity and diminished behavioral cocaine response. Our data demonstrate that Vav2 is a determinant of DAT trafficking in vivo and contributes to the maintenance of DA homeostasis in limbic DA neuron terminals. PMID- 26147535 TI - Adaptive strategies in nocturnally migrating insects and songbirds: contrasting responses to wind. AB - Animals that use flight as their mode of transportation must cope with the fact that their migration and orientation performance is strongly affected by the flow of the medium they are moving in, that is by the winds. Different strategies can be used to mitigate the negative effects and benefit from the positive effects of a moving flow. The strategies an animal can use will be constrained by the relationship between the speed of the flow and the speed of the animal's own propulsion in relation to the surrounding air. Here we analyse entomological and ornithological radar data from north-western Europe to investigate how two different nocturnal migrant taxa, the noctuid moth Autographa gamma and songbirds, deal with wind by analysing variation in resulting flight directions in relation to the wind-dependent angle between the animal's heading and track direction. Our results, from fixed locations along the migratory journey, reveal different global strategies used by moths and songbirds during their migratory journeys. As expected, nocturnally migrating moths experienced a greater degree of wind drift than nocturnally migrating songbirds, but both groups were more affected by wind in autumn than in spring. The songbirds' strategies involve elements of both drift and compensation, providing some benefits from wind in combination with destination and time control. In contrast, moths expose themselves to a significantly higher degree of drift in order to obtain strong wind assistance, surpassing the songbirds in mean ground speed, at the cost of a comparatively lower spatiotemporal migratory precision. Moths and songbirds show contrasting but adaptive responses to migrating through a moving flow, which are fine-tuned to the respective flight capabilities of each group in relation to the wind currents they travel within. PMID- 26147536 TI - Successful treatment of refractory pure red cell aplasia with bortezomib after allogeneic haematopoietic cell transplantation in a patient with alpha-beta subcutaneous panniculitis-like T cell lymphoma. PMID- 26147537 TI - Texting From the Bush: Data Collection Using SMS Text Messaging in Areas of Low Network Coverage From Low-Literacy Providers. AB - Mobile health technology, specifically Short Message Service (SMS), provides a low-cost medium to transmit data in real time. SMS has been used for data collection by highly literate and educated health care workers in low-resource countries; however, no previous studies have evaluated implementation of an SMS intervention by low-literacy providers. The Liberian Ministry of Health and Social Welfare identified a lack of accurate data on the number of pregnancies from rural areas. To capture these data from 11 rural communities in Liberia, 66 low-literate traditional midwives and 15 high-literate certified midwives were trained to report data via SMS. Data were reported via a 9-digit code sent from Java-based mobile phones. Study aims included determining the following components of SMS transmission: success rate, accuracy, predictors of successful transmission, and acceptance. Success rate of SMS transmission was significantly higher for certified midwives than for traditional midwives. The error rate was significantly higher for traditional midwives than for certified midwives. Years of education was the only predictor of successful SMS transmission. Traditional midwives and certified midwives accepted the intervention, although certified midwives found it easier to use. Certified midwives performed significantly better than did traditional midwives. SMS texting interventions should be targeted to health care workers with higher rates of literacy. PMID- 26147539 TI - The Relationship Between Cognitive Impairment and Global DNA Methylation Decrease Among Aluminum Potroom Workers. AB - OBJECTIVE: To investigate the relationship between cognitive impairment and global DNA methylation in aluminum (Al) potroom workers. METHODS: A total of 366 Al-exposed workers were investigated, and their cognitive functions were assessed with the Mini-Mental State Examination (MMSE). Aluminum in serum was quantified using graphite furnace atomic absorption spectrometry. Global DNA methylation was analyzed in whole blood using an enzyme-linked immunosorbent assay-like reaction. RESULTS: Mini-Mental State Examination scores and global DNA methylation decreased with the increase of serum Al concentration. Forty-three mild cognitive impairment (MCI) people were diagnosed. Global DNA methylation of the MCI was lower than the non-MCI. Multiple logistic analysis showed that the Al-exposed workers had lower global DNA methylation and higher serum Al concentration and were at the higher risk of MCI. CONCLUSIONS: Long-term exposure to Al may cause MCI. Mild cognitive impairment was significantly associated with global DNA methylation in blood. PMID- 26147538 TI - Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions. AB - OBJECTIVE: To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. METHODS: We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting-lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. RESULTS: B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. CONCLUSIONS: Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use. PMID- 26147540 TI - Barriers to Mental Health Service Use Among Workers With Depression and Work Productivity. AB - OBJECTIVE: This article estimates the decrease in workplace productivity losses associated with removal of three types of barriers to mental health service use among workers with depression. METHODS: A model of productivity losses based on the results of a population-based survey of Canadian workers was used to estimate the impact of three types of barriers to mental health service use among workers with depression. RESULTS: Removing the service need recognition barrier is associated with a 33% decrease in work productivity losses. There is a 49% decrease when all three barriers are removed. CONCLUSIONS: Our results suggest recognizing the need for treatment is only one barrier to service use; attitudinal and structural barriers should also be considered. The greatest decrease in productivity losses is observed with the removal of all three barriers. PMID- 26147541 TI - Recovery Processes During and After Work: Associations With Health, Work Engagement, and Job Performance. AB - OBJECTIVE: We examined energy management during work, recovery experiences after work and their connections to health, work engagement, and job performance. METHODS: An online survey was completed by 1208 Finnish employees. Energy management was assessed through 13 strategies and recovery experiences through four experiences. As outcomes of recovery, we examined self-reported health, work engagement, and job performance. RESULTS: On average, employees applied three energy management strategies. The most beneficial strategies were work-related: shifting focus, goal setting, and helping coworkers. Both energy management and recovery experiences contributed to the outcomes. CONCLUSIONS: Employees benefit in terms of energy from shifting their focus to positive aspects of their jobs and demonstrating proactive social behavior at work. Recovery processes during and after work are closely connected to each other, to well-being and performance at work. PMID- 26147543 TI - Health Impact Assessment of PM10 and PM2.5 in 27 Southeast and East Asian Cities. AB - OBJECTIVE: We aimed to evaluate the annual health impacts of particulate matter (PM) less than 10 MUm diameter (PM10) and less than 2.5-MUm diameter (PM2.5) in 27 cities in Southeast and East Asian countries (Japan, the Philippines, the Republic of Korea, Singapore, and Vietnam) for the year 2009 (n = 50,756,699). METHODS: We estimated the number of cases attributable to long-term exposure. We used a scenario that reduced the annual mean values for PM10 and PM2.5 to 20 and 10 MUg/m, respectively. RESULTS: A reduction in long-term exposure to PM10 and PM2.5 would have postponed 8% to 9% of all-cause mortality or about 37,000 deaths. One third of them were associated with cardiopulmonary mortality and one ninth of them were associated with lung cancer mortality. CONCLUSIONS: Current air pollution levels in Southeast and East Asian countries have a nonnegligible public health impact. PMID- 26147542 TI - Predictors Associated With Changes of Weight and Total Cholesterol Among Two Occupational Cohorts Over 10 Years. AB - OBJECTIVE: To ascertain worker health characteristics and psychosocial factors associated with changes in body weight and total cholesterol (TC) among two production operation populations. METHODS: We performed descriptive and predictive analysis of questionnaire data and biomedical measurements from two prospective cohort studies. Our key outcomes were changes in weight, and TC over 5 to 10 years between baseline and exit assessments. RESULTS: A total of 146 subjects were analyzed. Increases in weight were associated with belief in being overweight and baseline overweight and obesity. Increases in TC levels were associated with female sex, belief that TC levels were "not good," and feeling depressed. CONCLUSIONS: Most of the reported associations with increases in weight and TC levels are amenable to interventions and may be a target for workplace intervention programs. PMID- 26147544 TI - Creating a Representative Sample of Small Manufacturing Businesses for an Integrated Workplace Safety and Smoking Cessation Intervention Study. AB - OBJECTIVES: We aimed to recruit a representative sample of small manufacturing businesses (20 to 150 employees) for a group-randomized trial of an integrated workplace safety and smoking cessation program. METHODS: An initial sample was drawn from commercial databases, screened for duplicates or ineligibility, and contacted. Participating and nonparticipating businesses were compared on size, location, and type. Employee demographics of participating businesses were compared to a US Census Bureau database of similar businesses. RESULTS: From an initial sample of 2716 businesses, 328 were eligible and 47 (9%) agreed to participate. Participating companies tended to be larger. They were similar to employees in the Census Bureau dataset. CONCLUSIONS: Considerable resources were required to identify eligible businesses; commercial databases are the best resource but may not be comprehensive or current. The sample seemed to be representative of small manufacturing businesses in the study region. PMID- 26147545 TI - Absenteeism due to Functional Limitations Caused by Seven Common Chronic Diseases in US Workers. AB - OBJECTIVE: The study examined the relationship between functional limitation due to chronic diseases and absenteeism among full-time workers. The studied chronic diseases include arthritis/rheumatism, cancer, diabetes, heart disease, hypertension, lung disease, and stroke. METHODS: We analyzed data from the 2011 to 2013 National Health Interview Survey. Economic impact was determined by workdays lost and lost income. RESULTS: Increase in absenteeism was observed for each studied condition. Employees with multiple conditions also saw increase absenteeism. Employers lose 28.2 million workdays annually ($4.95 billion in lost income) due to functional limitation caused by chronic diseases. CONCLUSIONS: The results show a burden on society due to functional limitation caused by studied chronic diseases. Employers should look into implementing intervention/prevention programs, such as the Chronic Disease Self-Management Programs, to help reduce the cost associated with absenteeism. PMID- 26147548 TI - Perceived Age Discrimination at Work and Subsequent Long-Term Sickness Absence Among Finnish Employees. AB - OBJECTIVE: To investigate the association of perceived age discrimination at work with subsequent long-term sickness absence among Finnish employees. METHODS: A representative sample of Finnish employees (n = 6322) was merged with register based follow-up data. A negative binomial model was used in the analysis of subsequent sickness absence days. RESULTS: Perceived age discrimination was associated to long-term sickness absence after controlling various background, work, and health-related factors. CONCLUSIONS: Age discrimination at work is a significant risk factor for sickness absence. PMID- 26147547 TI - Is Obesity Associated With Adverse Workers' Compensation Claims Outcomes? A Pilot Study. AB - BACKGROUND: Obesity is associated with an increased risk for many chronic illnesses and disability. OBJECTIVE: To assess the relationship between obesity and delayed return to work and workers' compensation claim costs for both minor and significant injuries. METHOD: There were 1107 workers who filed a workers' compensation claim with the Louisiana Workers' Compensation Corporation in 2011 that were followed up to the end of the first quarter of 2014. RESULT: Adjusting for sex, age, marital status, and attorney involvement, the odds ratio of an obese versus normal weight claimant returning to work after a severe injury was 3.58 (95% confidence interval, 1.26 to 10.14) and claim expenses $100,000 or more, 3.19 (95% confidence interval, 1.18 to 8.62). CONCLUSIONS: Obesity was associated with increased time lost from work and costs among workers' compensation claimants sustaining severe, but not minor injuries. PMID- 26147546 TI - Formaldehyde Exposure and Mortality Risks From Acute Myeloid Leukemia and Other Lymphohematopoietic Malignancies in the US National Cancer Institute Cohort Study of Workers in Formaldehyde Industries. AB - OBJECTIVES: To evaluate associations between cumulative and peak formaldehyde exposure and mortality from acute myeloid leukemia (AML) and other lymphohematopoietic malignancies. METHODS: Cox proportional hazards analyses. RESULTS: Acute myeloid leukemia was unrelated to cumulative exposure. Hodgkin lymphoma relative risk estimates in the highest exposure categories of cumulative and peak exposures were, respectively, 3.76 (Ptrend = 0.05) and 5.13 (Ptrend = 0.003). There were suggestive associations with peak exposure observed for chronic myeloid leukemia, albeit based on very small numbers. No other lymphohematopoietic malignancy was associated with either chronic or peak exposure. CONCLUSIONS: Insofar as there is no prior epidemiologic evidence supporting associations between formaldehyde and either Hodgkin leukemia or chronic myeloid leukemia, any causal interpretations of the observed risk patterns are at most tentative. Findings from this re-analysis do not support the hypothesis that formaldehyde is a cause of AML. PMID- 26147549 TI - Effects of Social Determinants on Chinese Immigrant Food Service Workers' Work Performance and Injuries: Mental Health as a Mediator. AB - OBJECTIVE: The effects of social discrimination, job concerns, and social support on worker mental health and the influence of mental health on occupational health outcomes have been documented intermittently. We propose an integrated, theory driven model to distinguish the impact of social determinants on work performance and injuries and the mediating effects of mental health problems. METHODS: The US Chinese immigrant food service workers (N = 194) completed a multimeasure interview; we tested the integrated model using structural equation modeling. RESULTS: Mental health problems, which were associated with decreased work performance and increased injuries, also mediated relationships between job/employment concerns and both work performance and injuries but did not mediate the influences of discrimination and social support. CONCLUSIONS: This research reveals mechanisms by which social determinants influence immigrant worker health, pointing to complementary strategies for reducing occupational health disparities. PMID- 26147550 TI - Industry-Related Injuries in the United States From 1998 to 2011: Characteristics, Trends, and Associated Health Care Costs. AB - OBJECTIVE: To describe the trends, correlates, and healthcare costs associated with industry-related injuries across the United States between 1998 and 2011. METHODS: A retrospective, cross-sectional analysis of hospital discharges was conducted using the National Inpatient Sample. We used the International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify accidents occurring in industrial settings. Joinpoint regression modeling was used to analyze trends. RESULTS: Most of the 357,716 inpatient hospitalizations were admissions from the emergency department (55%). Fractures were the most prevalent injuries (48.1%), whereas the lower and upper extremities were the most common injury sites (51.7%). The mean per admission cost of direct medical care was $12,849, with an overall downward trend in injuries during the study period. CONCLUSIONS: A comprehensive trend analysis of industry-related injuries is valuable to policymakers in formulating targeted strategies and allocating resources to address disparities at various levels. PMID- 26147553 TI - The Impact of Domestic Violence in the Workplace: Results From a Pan-Canadian Survey. AB - OBJECTIVE: When workers experience domestic violence (DV) at home, impacts are felt in the workplace; however, little research is available on this topic. METHODS: We conducted an online survey regarding the impacts of DV at work. RESULTS: A total of 8429 people completed the survey. More than a third of respondents reported experiencing DV; among them, more than a third reported that DV affected their ability to get to work, and more than half reported that it continued at or near work. Most reported that DV negatively affected their performance. Almost all respondents, regardless of DV experience, believed that it impacts victims' work lives. CONCLUSIONS: This research identifies the scope and impact of DV on workers and workplaces. The data should assist governments, unions, and employers to enact and evaluate proactive practices to address the impact of DV in the workplace. PMID- 26147554 TI - A 3-Year Workplace-Based Intervention Program to Control Noncommunicable Disease Risk Factors in Sousse, Tunisia. AB - OBJECTIVE: To assess the effectiveness of a 3-year workplace-based intervention program on the control of the main noncommunicable disease risk factors (poor nutrition, physical inactivity, and tobacco use) among the employees of Sousse, Tunisia. METHODS: We conducted a quasi-experimental study (pre- and postassessments with intervention and control groups) in six companies of the governorate of Sousse in Tunisia.The intervention program consisted of health education programs (eg, workshops, films and open sensitization days). We also scheduled free physical activity sessions and free smoking cessation consultations. RESULTS: Our intervention program showed meaningful improvement among the employees toward dietary and physical activity behaviors but not for tobacco use. CONCLUSIONS: Workplace is a crucial setting for health promotion, and future programs should consider a multisectoral approach to control the main noncommunicable disease risk factors. PMID- 26147555 TI - Mathematical Error in "The Effect of an e-Health Intervention Designed to Reduce Prolonged Occupational Sitting on Mean Arterial Pressure". PMID- 26147556 TI - Response to Mathematical Error in "The Effect of an e-Health Intervention Designed to Reduce Prolonged Occupational Sitting on Mean Arterial Pressure". PMID- 26147557 TI - Comment on "The Effect of an e-Health Intervention Designed to Reduce Prolonged Occupational Sitting on Mean Arterial Pressure". PMID- 26147558 TI - Response to Comment on "The Effect of an e-Health Intervention Designed to Reduce Prolonged Occupational Sitting on Mean Arterial Pressure". PMID- 26147559 TI - Comment on "HRCT/CT and Associated Spirometric Effects of Low Libby Amphibole Asbestos Exposure" by Lockey et al (2015). PMID- 26147560 TI - Response to Comment on "HRCT/CT and Associated Spirometric Effects of Low Libby Amphibole Asbestos Exposure" by Lockey et al (2015). PMID- 26147561 TI - ASG2 is a farnesylated DWD protein that acts as ABA negative regulator in Arabidopsis. AB - The tagging-via-substrate approach designed for the capture of mammal prenylated proteins was adapted to Arabidopsis cell culture. In this way, proteins are in vivo tagged with an azide-modified farnesyl moiety and captured thanks to biotin alkyne Click-iT(r) chemistry with further streptavidin-affinity chromatography. Mass spectrometry analyses identified four small GTPases and ASG2 (ALTERED SEED GERMINATION 2), a protein previously associated to the seed germination gene network. ASG2 is a conserved protein in plants and displays a unique feature that associates WD40 domains and tetratricopeptide repeats. Additionally, we show that ASG2 has a C-terminal CaaX-box that is farnesylated in vitro. Protoplast transfections using CaaX prenyltransferase mutants show that farnesylation provokes ASG2 nucleus exclusion. Moreover, ASG2 interacts with DDB1 (DAMAGE DNA BINDING protein 1), and the subcellular localization of this complex depends on ASG2 farnesylation status. Finally, germination and root elongation experiments reveal that asg2 and the farnesyltransferase mutant era1 (ENHANCED RESPONSE TO ABSCISIC ACID (ABA) 1) behave in similar manners when exposed to ABA or salt stress. To our knowledge, ASG2 is the first farnesylated DWD (DDB1 binding WD40) protein related to ABA response in Arabidopsis that may be linked to era1 phenotypes. PMID- 26147562 TI - Differential effects of prolonged exposure on posttraumatic stress disorder symptoms in female veterans. AB - OBJECTIVE: We compared the effect of Prolonged Exposure (PE) on posttraumatic stress disorder (PTSD) symptom clusters and individual symptoms relative to a nonspecific comparison therapy (present-centered therapy; PCT) to identify the unique benefits of PE. We used data from a 12-site randomized clinical trial that found PE to be more effective than PCT for reducing PTSD symptom severity. METHOD: Participants were 284 female veterans and active duty soldiers with PTSD (M age = 44.8 years, range = 22-78; 45.4% non-White). Participants were randomized to 10 weekly sessions of PE or PCT and assessed before and after treatment and at 3- and 6-month follow-ups. The primary measure of PTSD symptoms and symptom clusters (reexperiencing, avoidance, numbing, and hyperarousal) was the Clinician-Administered PTSD Scale (CAPS; Weathers et al., 2001) but we also assessed self-reported PTSD using the PTSD Checklist-Specific Version (PCL; Weathers, Litz, Herman, Huska, & Keane, 1993). RESULTS: Almost all clinician rated and self-reported symptoms improved from pre- to posttreatment in both conditions. In the analyses of clinician-rated PTSD, PE had greater benefit than PCT on avoidance and numbing clusters. PE also had greater benefit on most individual symptoms in these clusters as well as on distress related to reminders. In the analyses of self-reported PTSD, PE had greater benefit than PCT on all clusters and on most individual symptoms. CONCLUSION: PE may be especially helpful for individuals with significant avoidance and numbing. Giving patients information about how a treatment can help with the symptoms that create the greatest burden can facilitate choosing the treatment that is best for them. PMID- 26147563 TI - LGB-affirmative cognitive-behavioral therapy for young adult gay and bisexual men: A randomized controlled trial of a transdiagnostic minority stress approach. AB - OBJECTIVES: We tested the preliminary efficacy of a transdiagnostic cognitive behavioral treatment adapted to improve depression, anxiety, and co-occurring health risks (i.e., alcohol use, sexual compulsivity, condomless sex) among young adult gay and bisexual men. Treatment adaptations focused on reducing minority stress processes that underlie sexual orientation-related mental health disparities. METHOD: Young gay and bisexual men (n = 63; M age = 25.94) were randomized to immediate treatment or a 3-month waitlist. At baseline, 3-month, and 6-month assessments, participants completed self-reports of mental health and minority stress and an interview of past-90-day risk behavior. RESULTS: Compared to waitlist, treatment significantly reduced depressive symptoms (b = -2.43, 95% CI: -4.90, 0.35, p < .001), alcohol use problems (b = -3.79, 95% CI: -5.94, 1.64, p < .001), sexual compulsivity (b = -5.09, 95% CI: -8.78, -1.40, p < .001), and past-90-day condomless sex with casual partners (b = -1.09, 95% CI: -1.80, 0.37, p < .001), and improved condom use self-efficacy (b = 10.08, 95% CI: 3.86, 16.30, p < .001). The treatment yielded moderate and marginally significant greater improvements than waitlist in anxiety symptoms (b = -2.14, 95% CI: -4.61, 0.34, p = .09) and past-90-day heavy drinking (b = -0.32, 95% CI: -0.71, 0.07, p = .09). Effects were generally maintained at follow-up. Minority stress processes showed small improvements in the expected direction. CONCLUSION: This study demonstrated preliminary support for the first intervention adapted to address gay and bisexual men's co-occurring health problems at their source in minority stress. If found to be efficacious compared to standard evidence-based treatments, the treatment will possess substantial potential for helping clinicians translate LGB-affirmative treatment guidelines into evidence-based practice. (PsycINFO Database Record PMID- 26147564 TI - Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies. AB - OBJECTIVE: Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed. METHODS: We performed a retrospective analysis of the first seven cases referred to our laboratory for exome sequencing following fetal demise or termination of pregnancy. All seven pregnancies had multiple congenital anomalies identified by level II ultrasound. Exome sequencing was performed on trios using cultured amniocytes or products of conception from the affected fetuses. RESULTS: Relevant alterations were identified in more than half of the cases (4/7). Three of the four were categorized as 'positive' results, and one of the four was categorized as a 'likely positive' result. The provided diagnoses included osteogenesis imperfecta II (COL1A2), glycogen storage disease IV (GBE1), oral facial-digital syndrome 1 (OFD1), and RAPSN-associated fetal akinesia deformation sequence. CONCLUSION: This data suggests that exome sequencing is likely to be a valuable diagnostic testing option for pregnancies with multiple congenital anomalies detected by prenatal ultrasound; however, additional studies with larger cohorts of affected pregnancies are necessary to confirm these findings. PMID- 26147565 TI - Correlations between clinical and pathological features in 17 cases of mycosis fungoides before and after transformation. AB - BACKGROUND: Mycosis fungoides (MF) may progress to transformed MF (T-MF), a condition with aggressive behavior. OBJECTIVES: This study was designed to compare the clinical and pathological features of biopsies in 17 cases of MF before and after transformation. METHODS: During a revision of primary cutaneous T cell lymphomas, 53 cases of MF were identified, including 17 cases of T-MF. Clinical, pathological, and immunohistochemical data for the MF patients were evaluated. Cases of T-MF and intermediate transformed (IT) MF were diagnosed according to previous criteria. The histological and immunohistochemical features of T-MF biopsies were compared with those of MF/IT-MF biopsies taken before or concomitant with transformation. RESULTS: At the initial diagnosis, three patients were found to have more advanced stages of disease: two had MF and T-MF simultaneously, and another had only oral T-MF. Four patients considered to show histological transformation maintained disease stages Ia and Ib and all remain alive. Of five patients with IT-MF at first diagnosis, all progressed to complete histological transformation, three developed tumors, and two died of disease. Four patients progressed to CD30+ large cell lymphoma, and three of these died of disease. In one of these patients, the MF biopsy showed a high level of expression of CD30 in the epidermis and dermis. CONCLUSIONS: No correlation between advanced MF and expression of CD25 and CD30, or frequency of Ki-67+ cells was found. The frequency of transformation among patients with initially non transformed MF was high. Our findings support the emphasis given by other authors to IT-MF, a pattern of MF which is generally not considered in many studies. PMID- 26147566 TI - Downstaging: Looking for answers, generating more questions? PMID- 26147568 TI - Authors' reply to comments on "a cautionary note concerning the use of stabilized weights in marginal structural models". PMID- 26147569 TI - Comments on 'A modest proposal for dropping poor arms in clinical trials' by Proschan and Dodd. PMID- 26147567 TI - IFNgamma and IL-12 Restrict Th2 Responses during Helminth/Plasmodium Co-Infection and Promote IFNgamma from Th2 Cells. AB - Parasitic helminths establish chronic infections in mammalian hosts. Helminth/Plasmodium co-infections occur frequently in endemic areas. However, it is unclear whether Plasmodium infections compromise anti-helminth immunity, contributing to the chronicity of infection. Immunity to Plasmodium or helminths requires divergent CD4+ T cell-driven responses, dominated by IFNgamma or IL-4, respectively. Recent literature has indicated that Th cells, including Th2 cells, have phenotypic plasticity with the ability to produce non-lineage associated cytokines. Whether such plasticity occurs during co-infection is unclear. In this study, we observed reduced anti-helminth Th2 cell responses and compromised anti helminth immunity during Heligmosomoides polygyrus and Plasmodium chabaudi co infection. Using newly established triple cytokine reporter mice (Il4gfpIfngyfpIl17aFP635), we demonstrated that Il4gfp+ Th2 cells purified from in vitro cultures or isolated ex vivo from helminth-infected mice up-regulated IFNgamma following adoptive transfer into Rag1-/- mice infected with P. chabaudi. Functionally, Th2 cells that up-regulated IFNgamma were transcriptionally re wired and protected recipient mice from high parasitemia. Mechanistically, TCR stimulation and responsiveness to IL-12 and IFNgamma, but not type I IFN, was required for optimal IFNgamma production by Th2 cells. Finally, blockade of IL-12 and IFNgamma during co-infection partially preserved anti-helminth Th2 responses. In summary, this study demonstrates that Th2 cells retain substantial plasticity with the ability to produce IFNgamma during Plasmodium infection. Consequently, co-infection with Plasmodium spp. may contribute to the chronicity of helminth infection by reducing anti-helminth Th2 cells and converting them into IFNgamma secreting cells. PMID- 26147570 TI - A Century of Shope Papillomavirus in Museum Rabbit Specimens. AB - Sylvilagus floridanus Papillomavirus (SfPV) causes growth of large horn-like tumors on rabbits. SfPV was described in cottontail rabbits (probably Sylvilagus floridanus) from Kansas and Iowa by Richard Shope in 1933, and detected in S. audubonii in 2011. It is known almost exclusively from the US Midwest. We explored the University of Kansas Natural History Museum for historical museum specimens infected with SfPV, using molecular techniques, to assess if additional wild species host SfPV, and whether SfPV occurs throughout the host range, or just in the Midwest. Secondary aims were to detect distinct strains, and evidence for strain spatio-temporal specificity. We found 20 of 1395 rabbits in the KU collection SfPV symptomatic. Three of 17 lagomorph species (S. nuttallii, and the two known hosts) were symptomatic, while Brachylagus, Lepus and eight additional Sylvilagus species were not. 13 symptomatic individuals were positive by molecular testing, including the first S. nuttallii detection. Prevalence of symptomatic individuals was significantly higher in Sylvilagus (1.8%) than Lepus. Half of these specimens came from Kansas, though new molecular detections were obtained from Jalisco-Mexico's first-and Nebraska, Nevada, New Mexico, and Texas, USA. We document the oldest lab-confirmed case (Kansas, 1915), pre-dating Shope's first case. SfPV amplification was possible from 63.2% of symptomatic museum specimens. Using multiple methodologies, rolling circle amplification and, multiple isothermal displacement amplification in addition to PCR, greatly improved detection rates. Short sequences were obtained from six individuals for two genes. L1 gene sequences were identical to all previously detected sequences; E7 gene sequences, were more variable, yielding five distinct SfPV1 strains that differing by less than 2% from strains circulating in the Midwest and Mexico, between 1915 and 2005. Our results do not clarify whether strains are host species specific, though they are consistent with SfPV specificity to genus Sylvilagus. PMID- 26147572 TI - Change Points in the Population Trends of Aerial-Insectivorous Birds in North America: Synchronized in Time across Species and Regions. AB - North American populations of aerial insectivorous birds are in steep decline. Aerial insectivores (AI) are a group of bird species that feed almost exclusively on insects in flight, and include swallows, swifts, nightjars, and flycatchers. The causes of the declines are not well understood. Indeed, it is not clear when the declines began, or whether the declines are shared across all species in the group (e.g., caused by changes in flying insect populations) or specific to each species (e.g., caused by changes in species' breeding habitat). A recent study suggested that population trends of aerial insectivores changed for the worse in the 1980s. If there was such a change point in trends of the group, understanding its timing and geographic pattern could help identify potential causes of the decline. We used a hierarchical Bayesian, penalized regression spline, change point model to estimate group-level change points in the trends of 22 species of AI, across 153 geographic strata of North America. We found evidence for group level change points in 85% of the strata. Change points for flycatchers (FC) were distinct from those for swallows, swifts and nightjars (SSN) across North America, except in the Northeast, where all AI shared the same group-level change points. During the 1980s, there was a negative change point across most of North America, in the trends of SSN. For FC, the group-level change points were more geographically variable, and in many regions there were two: a positive change point followed by a negative change point. This group-level synchrony in AI population trends is likely evidence of a response to a common environmental factor(s) with similar effects on many species across broad spatial extents. The timing and geographic patterns of the change points that we identify here should provide a spring-board for research into the causes behind aerial insectivore declines. PMID- 26147571 TI - Altered Resting-State Brain Activity and Connectivity in Depressed Parkinson's Disease. AB - Depressive symptoms are common in Parkinson's disease (PD), but the neurophysiological mechanisms of depression in PD are poorly understood. The current study attempted to examine disrupted spontaneous local brain activities and functional connectivities that underlie the depression in PD. We recruited a total of 20 depressed PD patients (DPD), 40 non-depressed PD patients (NDPD) and 43 matched healthy controls (HC). All the subjects underwent neuropsychological tests and resting-state fMRI scanning. The between-group differences in the amplitude of low frequency fluctuations (ALFF) of BOLD signals were examined using post-hoc tests after the analysis of covariance. Compared with the NDPD and HC, the DPD group showed significantly increased ALFF in the left median cingulated cortex (MCC). The functional connectivity (FC) between left MCC and all the other voxels in the brain were then calculated. Compared with the HC and NDPD group, the DPD patients showed stronger FC between the left MCC and some of the major nodes of the default mode network (DMN), including the post cingulated cortex/precuneus, medial prefrontal cortex, inferior frontal gyrus, and cerebellum. Correlation analysis revealed that both the ALFF values in the left MCC and the FC between the left MCC and the nodes of DMN were significantly correlated with the Hamilton Depression Rating Scale score. Moreover, higher local activities in the left MCC were associated with increased functional connections between the MCC and the nodes of DMN in PD. These abnormal activities and connectivities of the limbic-cortical circuit may indicate impaired high order cortical control or uncontrol of negative mood in DPD, which suggested a possible neural mechanism of the depression in PD. PMID- 26147573 TI - Identification and Antimicrobial Resistance of Bacteria Isolated from Probiotic Products Used in Shrimp Culture. AB - Probiotics are increasingly used in aquaculture to control diseases and improve feed digestion and pond water quality; however, little is known about the antimicrobial resistance properties of such probiotic bacteria and to what extent they may contribute to the development of bacterial resistance in aquaculture ponds. Concerns have been raised that the declared information on probiotic product labels are incorrect and information on bacterial composition are often missing. We therefore evaluated seven probiotics commonly used in Vietnamese shrimp culture for their bacterial species content, phenotypic antimicrobial resistance and associated transferable resistance genes. The bacterial species was established by 16S rRNA sequence analysis of 125 representative bacterial isolates. MIC testing was done for a range of antimicrobials and whole genome sequencing of six multiple antimicrobial resistant Bacillus spp. used to identify resistance genes and genetic elements associated with horizontal gene transfer. Thirteen bacterial species declared on the probiotic products could not be identified and 11 non-declared Bacillus spp. were identified. Although our culture-based isolation and identification may have missed a few bacterial species present in the tested products this would represent minor bias, but future studies may apply culture independent identification methods like pyro sequencing. Only 6/60 isolates were resistant to more than four antimicrobials and whole genome sequencing showed that they contained macrolide (ermD), tetracycline (tetL), phenicol (fexA) and trimethoprim (dfrD, dfrG and dfrK) resistance genes, but not known structures associated with horizontal gene transfer. Probiotic bacterial strains used in Vietnamese shrimp culture seem to contribute with very limited types and numbers of resistance genes compared to the naturally occurring bacterial species in aquaculture environments. Approval procedures of probiotic products must be strengthened through scientific-based efficacy trials and product labels should allow identification of individual bacterial strains and inform the farmer on specific purpose, dosage and correct application measures. PMID- 26147574 TI - Changes in Serum Levels of Myokines and Wnt-Antagonists after an Ultramarathon Race. AB - BACKGROUND: Regular physical activities have a positive effect on the muscular skeletal system but overstrenuous exercise may be different. Transiently suppressed bone formation and increased bone resorption after participation in a 246-km ultradistance race has been demonstrated. PURPOSE: The aim of this study was to analyze effects of the Spartathlon race on novel musculoskeletal markers. METHODS: Venous blood samples were obtained before and immediately after the race from 19 participants of the Spartathlon. From 9 runners who were available 3 days after the start blood was drawn for a third time. Serum levels of myostatin, an inhibitor of myogenic differentiation, and its opponent follistatin as well as sclerostin and dickkopf-1, both of them inhibitors of the wnt signaling pathway, and markers of bone turnover were determined. RESULTS: Serum levels of myostatin were significantly higher after the race. Serum follistatin only showed a transient increase. Sclerostin levels did not significantly differ before and after the race, whereas dickkopf-1 levels were significantly decreased. At follow up a decrement of sclerostin and dickkopf-1 levels was seen. Serum cathepsin K levels did not change. CONCLUSION: The increase of serum levels of myostatin appears to reflect muscle catabolic processes induced by overstrenuous exercise. After the short-term uncoupling of bone turnover participation in an ultradistance race seems to initiate a long-term positive effect on bone indicated by the low-level inhibition of the Wnt/beta-catenin signaling pathway. PMID- 26147576 TI - Delamination of graphite oxide in a liquid upon cooling. AB - Graphite oxide (GO) in liquid acetonitrile undergoes a transition from an ordered phase around ambient temperature to a gel-like disordered phase at temperatures below 260 K, as demonstrated by in situ X-ray diffraction. The stacking order of GO layers is restored below the freezing point of acetonitrile (199 K). The reversible swelling transition between a stacked crystalline phase and an amorphous delaminated state observed upon cooling provides an unusual example of increased structural disorder at lower temperatures. The formation of the gel like phase is attributed to the thermo-responsive conformational change of individual GO flakes induced by stronger solvation. Scanning force microscopy demonstrates that GO flakes deposited onto a solid substrate from acetonitrile dispersions at a temperature below 260 K exhibit corrugations and wrinkling which are not observed for the flakes deposited at ambient temperature. The thermo responsive transition between the delaminated and stacked phases reported here can be used for sonication-free dispersion of graphene oxide, micro-container applications, or the preparation of new composite materials. PMID- 26147575 TI - High-Dose alpha-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats. AB - Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (alpha-tocopherol; alphaT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of alphaT, we investigated the in vivo effects of alphaT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing alphaT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, alphaT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, alphaT-fed rats showed a tendency for an osteogenesis dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, alphaT consumption may have beneficial effects on bone health. PMID- 26147577 TI - Viability and MR detectability of iron labeled mesenchymal stem cells used for endoscopic injection into the porcine urethral sphincter. AB - Direct stem cell therapies for functionally impaired tissue require a sufficient number of cells in the target region and a method for verifying the fate of the cells in the subsequent time course. In vivo MRI of iron labeled mesenchymal stem cells has been suggested to comply with these requirements. The study was conducted to evaluate proliferation, migration, differentiation and adhesion effects as well as the obtained iron load of an iron labeling strategy for mesenchymal stem cells. After injection into the porcine urethral sphincter, the labeled cells were monitored for up to six months using MRI. Mesenchymal stem cells were labeled with ferucarbotran (60/100/200 ug/mL) and ferumoxide (200 ug/mL) for the analysis of migration and viability. Phantom MR measurements were made to evaluate effects of iron labeling. For short and long term studies, the iron labeled cells were injected into the porcine urethral sphincter and monitored by MRI. High resolution anatomical images of the porcine urethral sphincter were applied for detection of the iron particles with a turbo-spin-echo sequence and a gradient-echo sequence with multiple TE values. The MR images were then compared with histological staining. The analysis of cell function after iron labeling showed no effects on proliferation or differentiation of the cells. Although the adherence increases with higher iron dose, the ability to migrate decreases as a presumed effect of iron labeling. The iron labeled mesenchymal stem cells were detectable in vivo in MRI and histological staining even six months after injection. Labeling with iron particles and subsequent evaluation with highly resolved three dimensional data acquisition allows sensitive tracking of cells injected into the porcine urethral sphincter for several months without substantial biological effects on mesenchymal stem cells. PMID- 26147578 TI - Breast Cancer Screening, Incidence, and Mortality Across US Counties. AB - IMPORTANCE: Screening mammography rates vary considerably by location in the United States, providing a natural opportunity to investigate the associations of screening with breast cancer incidence and mortality, which are subjects of debate. OBJECTIVE: To examine the associations between rates of modern screening mammography and the incidence of breast cancer, mortality from breast cancer, and tumor size. DESIGN, SETTING, AND PARTICIPANTS: An ecological study of 16 million women 40 years or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results cancer registries during the year 2000. Of these women, 53,207 were diagnosed with breast cancer that year and followed up for the next 10 years. The study covered the period January 1, 2000, to December 31, 2010, and the analysis was performed between April 2013 and March 2015. EXPOSURES: Extent of screening in each county, assessed as the percentage of included women who received a screening mammogram in the prior 2 years. MAIN OUTCOMES AND MEASURES: Breast cancer incidence in 2000 and incidence-based breast cancer mortality during the 10-year follow-up. Incidence and mortality were calculated for each county and age adjusted to the US population. RESULTS: Across US counties, there was a positive correlation between the extent of screening and breast cancer incidence (weighted r = 0.54; P < .001) but not with breast cancer mortality (weighted r = 0.00; P = .98). An absolute increase of 10 percentage points in the extent of screening was accompanied by 16% more breast cancer diagnoses (relative rate [RR], 1.16; 95% CI, 1.13-1.19) but no significant change in breast cancer deaths (RR, 1.01; 95% CI, 0.96-1.06). In an analysis stratified by tumor size, we found that more screening was strongly associated with an increased incidence of small breast cancers (<=2 cm) but not with a decreased incidence of larger breast cancers (>2 cm). An increase of 10 percentage points in screening was associated with a 25% increase in the incidence of small breast cancers (RR, 1.25; 95% CI, 1.18-1.32) and a 7% increase in the incidence of larger breast cancers (RR, 1.07; 95% CI, 1.02-1.12). CONCLUSIONS AND RELEVANCE: When analyzed at the county level, the clearest result of mammography screening is the diagnosis of additional small cancers. Furthermore, there is no concomitant decline in the detection of larger cancers, which might explain the absence of any significant difference in the overall rate of death from the disease. Together, these findings suggest widespread overdiagnosis. PMID- 26147579 TI - Toward the Synthesis of Nuphar Sesquiterpene Thioalkaloids: Stereodivergent Rhodium-Catalyzed Synthesis of the Thiolane Subunit. AB - A stereodivergent approach to the central thiolane subunit of Nuphar sesquiterpene thioalkaloids has been developed. This approach features a rhodium catalyzed Stevens-type rearrangement in conjunction with an enzyme resolution reaction. Further elaboration into a polycyclic ring system via alcohol oxidation and ring-closing metathesis is also described. PMID- 26147580 TI - Temporal pattern of stimulation modulates reflex bladder activation by pudendal nerve stimulation. AB - AIMS: Reflex bladder activation and inhibition by electrical stimulation of pudendal nerve (PN) afferents is a promising approach to restore control of bladder function in persons with lower urinary tract dysfunction caused by disease or injury. The objective of this work was to determine whether bladder activation evoked by pudendal afferent stimulation was dependent on the temporal pattern of stimulation, and whether specific temporal patterns of stimulation produced larger bladder contractions than constant frequency stimulation. METHODS: The mean and maximum contraction pressures evoked by different temporal patterns of stimulation of the dorsal genital branch of the pudendal nerve were measured under isovolumetric conditions in alpha-chloralose anesthetized cats. A computational model of the spinal neural network mediating the pudendo-vesical reflex was used to understand the mechanisms of different bladder responses to patterned stimulation. RESULTS: The pattern of stimulation significantly affected the magnitude of evoked bladder contractions; several temporal patterns were as effective as regular stimulation, but no pattern evoked larger bladder contractions. Random patterns and patterns with pauses, burst-like activity, or high frequency components evoked significantly smaller bladder contractions, supporting the use of regular frequency stimulation in the development of neural prosthetic approaches for bladder control. CONCLUSIONS: These results reveal that the bladder response to pudendal afferent stimulation is dependent on the pattern, as well as the frequency, of stimulation. The computational model revealed that the effects of patterned pudendal afferent stimulation were determined by the dynamic properties of excitatory and inhibitory interneurons in the lumbosacral spinal cord. Neurourol. Urodynam. 35:882-887, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26147581 TI - Development of Radiolabeled Membrane Type-1 Matrix Metalloproteinase Activatable Cell Penetrating Peptide Imaging Probes. AB - Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP-14) plays an important role in adverse cardiac remodelling. Here, we aimed to develop radiolabeled activatable cell penetrating peptides (ACPP) sensitive to MT1-MMP for the detection of elevated MT1-MMP levels in adverse cardiac remodelling. Three ACPP analogs were synthesized and the most potent ACPP analog was selected using MT1 MMP sensitivity and enzyme specificity assays. This ACPP, called ACPP-B, showed high sensitivity towards MT1-MMP, soluble MMP-2, and MT2-MMP, while limited sensitivity was measured for other members of the MMP family. In in vitro cell assays, radiolabeled ACPP-B showed efficient cellular uptake upon activation. A pilot in vivo study showed increased uptake of the radiolabeled probe in regions of infarcted myocardium compared to remote myocardium, warranting further in vivo evaluation. PMID- 26147582 TI - Chemical Composition and Antioxidant and Antibacterial Activities of an Essential Oil Extracted from an Edible Seaweed, Laminaria japonica L. AB - Laminaria japonica L. is among the most commonly consumed seaweeds in northeast Asia. In the present study, L. japonica essential oil (LJEO) was extracted by microwave-hydrodistillation and analyzed by gas chromatography and mass spectroscopy. LJEO contained 21 volatile compounds, comprising 99.76% of the total volume of the essential oil, primarily tetradeconoic acid (51.75%), hexadecanoic acid (16.57%), (9Z,12Z)-9,12-Octadecadienoic acid (12.09%), and (9Z) hexadec-9-enoic acid (9.25%). Evaluation of the antibacterial potential against three foodborne pathogens, Bacillus cereus ATCC 10876, Escherichia coli O157:H7 ATCC 43890, and Staphylococcus aureus ATCC 49444, revealed that LJEO at a concentration of 25 mg/paper disc exerted high antibacterial activity against S. aureus (11.5 +/- 0.58 mm inhibition zone) and B. cereus (10.5 +/- 0.57 mm inhibition zone), but no inhibition of E. coli O157:H7. LJEO also displayed DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity (80.45%), superoxide anion scavenging activity (54.03%), and ABTS (2,2'-azino-bis(3 ethylbenzothiazoline-6-sulphonic acid) radical and hydroxyl radical scavenging at 500 ug/mL. Finally, LJEO showed high inhibition of lipid peroxidation with strong reducing power. In conclusion, LJEO from edible seaweed is an inexpensive but favorable resource with strong antibacterial capacity as well as free radical scavenging and antioxidant activity; therefore, it has the potential for use in the food, cosmetics, and pharmaceutical industries. PMID- 26147583 TI - Quantitative 1H-NMR Method for the Determination of Tadalafil in Bulk Drugs and its Tablets. AB - A simple, rapid, accurate, and selective quantitative nuclear magnetic resonance method for the determination of tadalafil in bulk drugs and its tablets was established and evaluated. Spectra were obtained in dimethylsulfoxide-d6 using 2,4-dinitrotoluene as the internal standard. In this study, the method's linearity, range, limit of quantification, stability, precision, and accuracy were validated. The results were consistent with those obtained from high performance liquid chromatography analysis. Thus, the proposed method is a useful and practical tool for the determination of tadalafil in bulk drugs and its tablets. PMID- 26147584 TI - Better therapy requires better response evaluation: Paving the way for minimal residual disease testing for every myeloma patient. AB - In 2015, there is a large body of evidence demonstrating that minimal residual disease (MRD) negativity after therapy is a powerful predictor of progression free survival and overall survival in multiple myeloma. On the basis of available data, we believe MRD provides a meaningful endpoint for regulatory purposes, academic studies, and a valuable prognostic evaluation of individual patients in the clinical setting. Similar to what has been shown in acute and chronic lymphocytic leukemia, based on emerging data, the prognostic impact of MRD in multiple myeloma appears to be independent of induction therapy received. This fact raises fundamental questions regarding best possible treatment strategies (e.g., fixed number of cycles versus response adapted number of cycles) as well as optimal treatment modalities (e.g., newer effective but less intense combination therapies versus high dose melphalan followed by autologous stem cell transplantation), in particular for patients newly diagnosed with multiple myeloma. PMID- 26147585 TI - Stable incorporation of alpha-smooth muscle actin into stress fibers is dependent on specific tropomyosin isoforms. AB - alpha-Smooth Muscle Actin (alpha-SMA), a widely characterized cytoskeletal protein, represents the hallmark of myofibroblast differentiation. Transforming growth factorbeta1 (TGFbeta1) stimulates alpha-SMA expression and incorporation into stress fibers, thus providing an increased myofibroblast contractile force that participates in tissue remodeling. We have addressed the molecular mechanism by which alpha-SMA is stably incorporated into stress fibers in human myofibroblasts following exposure to TGFbeta1. The unique N-terminal sequence AcEEED, which is critical for alpha-SMA incorporation into stress fibers, was used to screen for AcEEED binding proteins. Tropomyosins were identified as candidate binding proteins. We find that after TGFbeta1 treatment elevated levels of the Tpm1.6/7 isoforms, and to a lesser extent Tpm2.1, precede the increase in alpha-SMA. RNA interference experiments demonstrate that alpha-SMA fails to stably incorporate into stress fibers of TGFbeta1 treated fibroblasts depleted of Tpm1.6/7, but not other tropomyosins. This does not appear to be due to exclusive interactions between alpha-SMA and just the Tpm1.6/7 isoforms. We propose that an additional AcEEED binding factor may be required to generate alpha-SMA filaments containing just Tpm1.6/7 which result in stable incorporation of the resulting filaments into stress fibers. PMID- 26147586 TI - [Panendoscopy]. PMID- 26147588 TI - Vitamin D and C-Reactive Protein: A Mendelian Randomization Study. AB - Vitamin D deficiency is widely prevalent and has been associated with many diseases. It has been suggested that vitamin D has effects on the immune system and inhibits inflammation. The aim of our study was to investigate whether vitamin D has an inhibitory effect on systemic inflammation by assessing the association between serum levels of vitamin D and C-reactive protein. We studied the association between serum 25-hydroxyvitamin D and C-reactive protein through linear regression in 9,649 participants of the Rotterdam Study, an observational, prospective population-based cohort study. We used genetic variants related to vitamin D and CRP to compute a genetic risk score and perform bi-directional Mendelian randomization analysis. In linear regression adjusted for age, sex, cohort and other confounders, natural log-transformed CRP decreased with 0.06 (95% CI: -0.08, -0.03) unit per standard deviation increase in 25-hydroxyvitamin D. Bi-directional Mendelian randomization analyses showed no association between the vitamin D genetic risk score and lnCRP (Beta per SD = -0.018; p = 0.082) or the CRP genetic risk score and 25-hydroxyvitamin D (Beta per SD = 0.001; p = 0.998). In conclusion, higher levels of Vitamin D are associated with lower levels of C-reactive protein. In this study we did not find evidence for this to be the result of a causal relationship. PMID- 26147590 TI - Factor Structure of the Binge Eating Scale in a Large Sample of Obese and Overweight Patients Attending Low Energy Diet Therapy. AB - In the present study, we evaluated the dimensionality and psychometric properties of the Italian version of the Binge Eating Scale (BES) in a 669 (127 men and 542 women) obese and overweight patients seeking weight loss treatment. All participants were administered the Italian version of the BES. Fit statistics for the alternative SEM models demonstrated that both the one-factor and competing two-factor models had a comparable fit to the data. Thus, we selected the one factor model as the most parsimonious. The BES had good internal consistency reliability (alpha = 0.89) with a moderate mean inter-item correlation (rii = 0.34). Given that we were not able to clearly determine the best model among the competing two-factor models and a comparable fit of these models with the one factor model, we have suggested that the one-factor model is the best fitting model describing the dimensionality of the BES. PMID- 26147592 TI - Mapping the Complex Phase Behaviors of Aqueous Mixtures of kappa-Carrageenan and Type B Gelatin. AB - We report a detailed and complete phase diagram for an aqueous mixture of oppositely charged gelling biopolymers, type B gelatin and kappa-carrageenan (KC) at pH 7.0. The phase diagram is studied in the ionic strength-temperature coordinate by means of turbidity, rheological and differential scanning calorimetric measurements, and macroscopic phase compositional analysis. Seven phase regions are identified, including (I) compatible region, (II) electrostatically induced associative phase separation (EIAPS) region, (III) hydrogen bonding induced associative phase separation (HBIAPS) region, (IV) coexistence of EIAPS and HBIAPS, (V) segregative phase separation (SPS) region, (VI) coexistence of HBIAPS and SPS, and (VII) SPS trapped by gelation. The HBIAPS reported for the first time here is attributed to the extensive hydrogen bonding formation between gelatin and KC above their conformational transition temperatures, as probed by addition of urea and methylene blue as well as by 2D (1)H-(1)H NOESY NMR. NaCl is found to have dual effects on HBIAPS. The electrostatic complexation at lower ionic strength facilitates the formation of hydrogen bonds between gelatin and KC and hence the HBIAPS. It is believed that the local structural arrangement of gelatin molecules or the change in local solvent environment prior to triple helix formation during cooling enables the formation of hydrogen bonds with KC. PMID- 26147591 TI - Small GTPases promote actin coat formation on microsporidian pathogens traversing the apical membrane of Caenorhabditis elegans intestinal cells. AB - Many intracellular pathogens co-opt actin in host cells, but little is known about these interactions in vivo. We study the in vivo trafficking and exit of the microsporidian Nematocida parisii, which is an intracellular pathogen that infects intestinal cells of the nematode Caenorhabditis elegans. We recently demonstrated that N. parisii uses directional exocytosis to escape out of intestinal cells into the intestinal tract. Here, we show that an intestinal specific isoform of C. elegans actin called ACT-5 forms coats around membrane compartments that contain single exocytosing spores, and that these coats appear to form after fusion with the apical membrane. We performed a genetic screen for host factors required for actin coat formation and identified small GTPases important for this process. Through analysis of animals defective in these factors, we found that actin coats are not required for pathogen exit although they may boost exocytic output. Later during infection, we find that ACT-5 also forms coats around membrane-bound vesicles that contain multiple spores. These vesicles are likely formed by clathrin-dependent compensatory endocytosis to retrieve membrane material that has been trafficked to the apical membrane as part of the exocytosis process. These findings provide insight into microsporidia interaction with host cells, and provide novel in vivo examples of the manner in which intracellular pathogens co-opt host actin during their life cycle. PMID- 26147593 TI - Post-transplant lymphoproliferative disorders with naso- and oropharyngeal manifestation. AB - The nasopharyngeal/oropharyngeal lymphatic tissues represent the anatomical site of Epstein-Barr virus (EBV) entry. Post-transplant lymphoproliferative disorders (PTLD) are often associated with EBV, but little is known about the characteristics of nasopharyngeal/oropharyngeal mass-forming PTLD. Retrospective evaluation of our own PTLD database (n = 79) and the PubMed((r)) database (n = 61) has been performed. Sinonasal/oro-/nasopharyngeal lymphatic masses were early lesions (n = 54/140, 38.5%), polymorphic PTLD (n = 32/140, 23%), monomorphic B PTLD (n = 47/140, 33.5%) and T-PTLD (n = 7/140, 5%). One-fourth of lesions manifested as masses in the Waldeyer's ring, and in two-thirds of cases, swelling of tonsils was related to manifestation of benign early lesions. Tonsil infiltration by polymorphic PTLD and monomorphic PTLD was present in one-third of cases. Extratonsillar masses were mainly monomorphic PTLD. Meta-analysis of our data in combination with previously published data revealed that lung transplantation and young patients are at a higher risk for earlier manifestation of monomorphic PTLD. Therapy is similar to PTLD therapy strategies, in general reduced immunosuppression and chemotherapy for polymorphic and monomorphic PTLD, and diagnostic and therapeutic surgical gross tumour resection of tonsillar/adenoid lesions. In summary, it is relevant for the clinical differential diagnosis that oro-/nasopharyngeal aggressive PTLD manifested in ~30% as tonsillar masses and >90% at extratonsillar sites. PMID- 26147594 TI - Echocardiographic Evaluation of Changes in Cardiac Hemodynamics and Loading Conditions after Transthoracic Minimally Invasive Device Closure of Atrial Septal Defect. AB - PURPOSE: To evaluate transthoracic minimally invasive device closure of atrial septal defects by performing transthoracic echocardiography to measure changes in cardiac hemodynamics and loading conditions. METHODS: Between January 2012 and December 2012, we performed transthoracic minimally invasive device closure of atrial septal defects in 95 patients with secundum atrial septal defects (ASD), and performed transthoracic echocardiography to measure blood flow velocities at the tricuspid valve orifice and at the pulmonary valve orifice, sizes of the left and right atria and ventricles, right ventricular fractional area change, right ventricular Tei index, three-dimensional right ventricular ejection fraction, tricuspid annular plane systolic excursion and left ventricular ejection fractions before the procedure and 1 week, 3 months, and 1 year post-procedure. RESULTS: Varying degrees of improvement were observed post-procedure at later time points. The maximum blood flow velocity at the pulmonary valve orifice, mean flow velocity, velocity-time integral, and A peak and E peak blood flow velocity at the tricuspid valve orifice decreased significantly post-procedure (P<0.05). In 3 months and 1 year's follow-up, the inner diameter of the middle portion of the pulmonary artery, and diameters of the right atrium and right ventricle decreased significantly post-procedure (P<0.05). The diameters of the left atrium and left ventricle increased after the procedure (P<0.05). One week after the procedure, the right ventricular fractional area change, three-dimensional right ventricular ejection fraction, right ventricular Tei index and tricuspid annular plane systolic excursion had significantly reduced compared with the preoperative data (P<0.05). While these four parameters were still decreased at the 3 months and at 1 year's follow-up, but the differences were not statistically significant compared with the 1 week's postoperative data (P>0.05). One week post-procedure, left ventricular ejection fraction had not changed significantly, but at 3 months and at 1 year post-procedure, left ejection fraction had increased significantly compared with the preoperative data (P<0.05). CONCLUSION: Echocardiographic evaluation has demonstrated that cardiac hemodynamics and loading conditions improved significantly after transthoracic minimally invasive device closure of atrial septal defects. PMID- 26147595 TI - Occurrence, genotypic characterization, and patterns of shedding of human polyomavirus JCPyV and BKPyV in urine samples of healthy individuals in Sao Paulo, Brazil. AB - The objective of this study was to evaluate the prevalence, genotypic characterization, and determination of the patterns of shedding of human polyomavirus JC (JCPyV) and BK (BKPyV) in consecutive urine samples collected from healthy adults. Urine samples collected monthly over a 6 month period were screened by polymerase chain reaction (PCR) with two sets of primers complementary to the VP1 protein region specific for the JCPyV or BKPyV genome. The viral load of JCPyV and BKPyV in positive samples was determined by quantitative real time PCR. Seventy-one healthy individuals (ages between 18 and 65) were included in the study. Polyomavirus DNA urinary shedding was identified in 44 (62%) of the 71 individuals evaluated: BKPyV only in 16 (22.5%); JCPyV only in 19 (26.7%); and both in 9 (12.7%). Among the 28 individuals shedding JCPyV, the shedding was nearly continuous in 13 (46.4%) and sporadic in 15 (53.6%), whereas all BKPyV shedding was sporadic. A total of 45 (19 BKPyV and 26 JCPyV) strains were identified. Of the BKPyV strains, individuals were observed that excreted all genotypes except genotype 3 and the JCPyV strains, excretion of 5 different genotypes. Evaluating the age of individuals who excrete JCPyV and BKPyV, mostly are young adults, with a slight increase with increasing age and observing the viral load can not draw any parallel between the increase or decrease of age or excreted genotype as there was a wide variation both in the excretion of BKPyV and JCPyV. The high occurrence of isolated or simultaneous urinary shedding of JCPyV and BKPyV in healthy individuals merits further study. PMID- 26147596 TI - Structure of Staphylococcal Enterotoxin E in Complex with TCR Defines the Role of TCR Loop Positioning in Superantigen Recognition. AB - T cells are crucial players in cell-mediated immunity. The specificity of their receptor, the T cell receptor (TCR), is central for the immune system to distinguish foreign from host antigens. Superantigens are bacterial toxins capable of inducing a toxic immune response by cross-linking the TCR and the major histocompatibility complex (MHC) class II and circumventing the antigen specificity. Here, we present the structure of staphylococcal enterotoxin E (SEE) in complex with a human T cell receptor, as well as the unligated T cell receptor structure. There are clear structural changes in the TCR loops upon superantigen binding. In particular, the HV4 loop moves to circumvent steric clashes upon complex formation. In addition, a predicted ternary model of SEE in complex with both TCR and MHC class II displays intermolecular contacts between the TCR alpha chain and the MHC, suggesting that the TCR alpha-chain is of importance for complex formation. PMID- 26147597 TI - Cytochrome P450 CYP 2C19*2 Associated with Adverse 1-Year Cardiovascular Events in Patients with Acute Coronary Syndrome. AB - BACKGROUND: The cytochrome P450 (CYP450) 2C19 681 genotypes affect the antiplatelet activity of clopidogrel. We investigated the correlation of CYP 2C19 681G > A mutation with clopidogrel resistance (CR). Additionally, we studied the effect of CR on clinical prognosis of patients with acute coronary syndrome (ACS). METHODS: One hundred ten ACS patients undergoing percutaneous coronary intervention, who were followed-up for 1 year, were included in the study. The patients were co-administered aspirin 100 mg/d and clopidogrel 75mg/d following a loading dose of 300 mg. CR was assessed on the basis of polymorphism observed in the CYP2C19 subgroup. RESULTS: Patients in GG genotype group exhibited greater inhibition of platelet aggregation than patients in GA and AA genotype groups (16.2 +/- 10.1%; 10.2 +/- 9.9%; 8.0 +/- 5.9%, respectively, p < 0.01). CYP2C19 681GG genotype group was associated with lower CR than CYP2C19 681A allele (GA + AA) group (9/59 vs. (12+5)/51; p = 0.009). Over a follow-up of 12 months, the incidence of recurrent angina, acute myocardial infarction, and intra-stent thrombosis in CYP2C19 681 GG carriers was significantly lower than that in CYP2C19 681A allele (GA + AA) group (2/59 vs. 8/51, 1/59 vs. 6/51, 0 vs. 4/51, respectively, p < 0.05). CONCLUSION: CYP 2C19*2 is associated with reduced clopidogrel antiplatelet activity and might be an important marker for poor prognosis of ACS. PMID- 26147598 TI - Missed Opportunities along the Prevention of Mother-to-Child Transmission Services Cascade in South Africa: Uptake, Determinants, and Attributable Risk (the SAPMTCTE). AB - OBJECTIVES: We examined uptake of prevention of mother-to-child HIV transmission (PMTCT) services, predictors of missed opportunities, and infant HIV transmission attributable to missed opportunities along the PMTCT cascade across South Africa. METHODS: A cross-sectional survey was conducted among 4-8 week old infants receiving first immunisations in 580 nationally representative public health facilities in 2010. This included maternal interviews and testing infants' dried blood spots for HIV. A weighted analysis was performed to assess uptake of antenatal and perinatal PMTCT services along the PMTCT cascade (namely: maternal HIV testing, CD4 count test/result, and receiving maternal and infant antiretroviral treatment) and predictors of dropout. The population attributable fraction associated with dropouts at each service point are estimated. RESULTS: Of 9,803 mothers included, 31.7% were HIV-positive as identified by reactive infant antibody tests. Of these 80.4% received some form of maternal and infant antiretroviral treatment. More than a third (34.9%) of mothers dropped out from one or more steps in the PMTCT service cascade. In a multivariable analysis, the following characteristics were associated with increased dropout from the PMTCT cascade: adolescent (<20 years) mothers, low socioeconomic score, low education level, primiparous mothers, delayed first antenatal visit, homebirth, and non disclosure of HIV status. Adolescent mothers were twice (adjusted odds ratio: 2.2, 95% confidence interval: 1.5-3.3) as likely to be unaware of their HIV positive status and had a significantly higher rate (85.2%) of unplanned pregnancies compared to adults aged >=20 years (55.5%, p = 0.0001). A third (33.8%) of infant HIV infections were attributable to dropout in one or more steps in the cascade. CONCLUSION: A third of transmissions attributable to missed opportunities of PMTCT services can be prevented by optimizing the uptake of PMTCT services. Identified risk factors for low PMTCT service uptake should be addressed through health facility and community-level interventions, including raising awareness, promoting women education, adolescent focused interventions, and strengthening linkages/referral-system between communities and health facilities. PMID- 26147599 TI - Development and Validation of a Real-Time PCR Assay for Rapid Detection of Two Spotted Spider Mite, Tetranychus urticae (Acari: Tetranychidae). AB - Spider mites of the genus Tetranychus are difficult to identify due to their limited diagnostic characters. Many of them are morphologically similar and males are needed for species-level identification. Tetranychus urticae is a common interception and non-regulated pest at New Zealand's borders, however, most of the intercepted specimens are females and the identification was left at Tetranychus sp. Consequently, the shipments need to be fumigated. DNA sequencing and PCR-restriction fragment length polymorphism (PCR-RFLP) protocols could be used to facilitate the accurate identification. However, in the context of border security practiced in New Zealand, insect identifications are required to be provided within four hours of receiving the samples; thus, those molecular methods are not sufficient to meet this requirement. Therefore, a real-time PCR TaqMan assay was developed for identification of T. urticae by amplification of a 142 bp Internal Transcribed Spacer (ITS) 1 sequence. The developed assay is rapid, detects all life stages of T. urticae within three hours, and does not react with closely related species. Plasmid DNA containing ITS1 sequence of T. uritcae was serially diluted and used as standards in the real-time PCR assay. The quantification cycle (Cq) value of the assay depicted a strong linear relationship with T. urticae DNA content, with a regression coefficient of 0.99 and efficiency of 98%. The detection limit was estimated to be ten copies of the T. urticae target region. The assay was validated against a range of T. urticae specimens from various countries and hosts in a blind panel test. Therefore the application of the assay at New Zealand will reduce the unnecessary fumigation and be beneficial to both the importers and exporters. It is expected that the implementation of this real-time PCR assay would have wide applications in diagnostic and research agencies worldwide. PMID- 26147600 TI - Identifying evidence for public health guidance: a comparison of citation searching with Web of Science and Google Scholar. AB - AIM: To examine how effectively forwards citation searching with Web of Science (WOS) or Google Scholar (GS) identified evidence to support public health guidance published by the National Institute for Health and Care Excellence. METHOD: Forwards citation searching was performed using GS on a base set of 46 publications and replicated using WOS. OUTCOMES: WOS and GS were compared in terms of recall; precision; number needed to read (NNR); administrative time and costs; and screening time and costs. Outcomes for all publications were compared with those for a subset of highly important publications. RESULTS: The searches identified 43 relevant publications. The WOS process had 86.05% recall and 1.58% precision. The GS process had 90.7% recall and 1.62% precision. The NNR to identify one relevant publication was 63.3 with WOS and 61.72 with GS. There were nine highly important publications. WOS had 100% recall, 0.38% precision and NNR of 260.22. GS had 88.89% recall, 0.33% precision and NNR of 300.88. Administering the WOS results took 4 h and cost L88-L136, compared with 75 h and L1650-L2550 with GS. CONCLUSION: WOS is recommended over GS, as citation searching was more effective, while the administrative and screening times and costs were lower. PMID- 26147601 TI - Characterization of the Prokaryotic Sodium Channel NavSp Pore with a Microfluidic Bilayer Platform. AB - This paper describes the use of a newly-developed micro-chip bilayer platform to examine the electrophysiological properties of the prokaryotic voltage-gated sodium channel pore (Na(v)Sp) from Silicibacter pomeroyi. The platform allows up to 6 bilayers to be analysed simultaneously. Proteoliposomes were incorporated into suspended lipid bilayers formed within the microfluidic bilayer chips. The chips provide access to bilayers from either side, enabling the fast and controlled titration of compounds. Dose-dependent modulation of the opening probability by the channel blocking drug nifedipine was measured and its IC50 determined. PMID- 26147602 TI - Serial reversal learning in gray squirrels: Learning efficiency as a function of learning and change of tactics. AB - Learning allows individuals to adapt their behaviors flexibly to a changing environment. When the same change recurs repeatedly, acquiring relevant tactics may increase learning efficiency. We examined this relationship, along with the effects of proactive interference and other interference information, in a serial spatial reversal task with 5 gray squirrels (Sciurus carolinensis). Squirrels completed an acquisition and 11 reversal phases with a poke box in which 2 of 4 possible reward locations were baited diagonally in a square array. In this situation, an efficient tactic is to locate the diagonally related locations consecutively (integrative search tactic) instead of searching rewards in a clockwise or counterclockwise direction (sequential search tactic). All squirrels formed a learning set, acquiring successive reversals in fewer trials. Although 4 squirrels gradually employed more integrative tactics in locating the rewards both within and between phases, sequential tactics were used in the first trial of each phase. This suggests the integrative tactic did not depend on an association between the rewarded locations but was learned as a spatial pattern and/or by use of extra-apparatus cues to locate individual rewards. Generalized estimating equation models showed that learning efficiency increased with experience and tactic change. Although tactic change partially mediated the effect of learning on learning efficiency, learning remained an independent contribution to improved efficiency. Squirrels that used more integrative tactics made fewer total errors than squirrels that used less integrative tactics, suggesting that learning a task-relevant tactic using spatial cues can provide direct benefits in maximizing rewards and minimizing time costs. PMID- 26147603 TI - When patterning discriminations are harder than biconditional ones: A cue constellation approach. AB - Recent attempts to distinguish configural from nonconfigural accounts of causal learning have compared the relative ease of learning 2 kinds of complex discriminations, a biconditional discrimination (e.g., AB+, CD+, AC0, and BD0), and a negative patterning discrimination, (e.g., A+, B+, and AB0), but have yielded conflicting results. Some studies have found the biconditional task to be easier than negative patterning and others have found negative patterning to be easier than the biconditional. This article evaluates these complex discriminations in several studies using a method that attempts to correct methodological problems that arise in comparisons of individual stimuli and stimulus compounds. Across several variations in procedure, negative patterning discriminations were significantly more difficult than biconditional discriminations. The research also found evidence in comparisons across studies that the difficulty of the biconditional, relative to a comparable nonconfigural compound discrimination, depended on whether the task emphasized configural or nonconfigural cues. The overall pattern of results appeared to be well accounted for by models that include configural information, suggesting that theories which invoke configural elements as a basis for learning complex discriminations remain viable explanatory frameworks. PMID- 26147605 TI - Lower plasma pantoprazole level predicts Helicobacter pylori treatment failure in patients with type 2 diabetes mellitus. AB - OBJECTIVE: We aimed to compare the plasma pantoprazole level (PPL) between patients with type 2 diabetes mellitus and non-diabetic patients during Helicobacter pylori (H. pylori) eradication treatment and to explore the role of PPL in predicting the treatment success rates. METHODS: This study included 40 diabetic and 40 non-diabetic treatment-naive H. pylori-infected patients. Bismuth based standard quadruple treatment for H. pylori eradication was used for 14 days in both groups. PPL was measured using the square-wave voltammetry method. RESULTS: H. pylori eradication rate (60.0% vs 87.5%, P = 0.005) and PPL (0.25 +/- 0.03 MUg/mL vs 0.34 +/- 0.03 MUg/mL, P < 0.001) was significantly lower in the diabetic group compared with the controls. Patients with treatment failure had lower PPL than those with successful treatment (P < 0.001). The receiver operating characteristics curve demonstrated that PPL had a significant predictive value for the outcome of H. pylori eradication. CONCLUSION: Type 2 diabetic patients had lower PPL than the non-diabetic controls, which led to their lower H. pylori eradication rates. PMID- 26147604 TI - Quantitative Analysis of NF-kappaB Transactivation Specificity Using a Yeast Based Functional Assay. AB - The NF-kappaB transcription factor family plays a central role in innate immunity and inflammation processes and is frequently dysregulated in cancer. We developed an NF-kappaB functional assay in yeast to investigate the following issues: transactivation specificity of NF-kappaB proteins acting as homodimers or heterodimers; correlation between transactivation capacity and in vitro DNA binding measurements; impact of co-expressed interacting proteins or of small molecule inhibitors on NF-kappaB-dependent transactivation. Full-length p65 and p50 cDNAs were cloned into centromeric expression vectors under inducible GAL1 promoter in order to vary their expression levels. Since p50 lacks a transactivation domain (TAD), a chimeric construct containing the TAD derived from p65 was also generated (p50TAD) to address its binding and transactivation potential. The p50TAD and p65 had distinct transactivation specificities towards seventeen different kappaB response elements (kappaB-REs) where single nucleotide changes could greatly impact transactivation. For four kappaB-REs, results in yeast were predictive of transactivation potential measured in the human MCF7 cell lines treated with the NF-kappaB activator TNFalpha. Transactivation results in yeast correlated only partially with in vitro measured DNA binding affinities, suggesting that features other than strength of interaction with naked DNA affect transactivation, although factors such as chromatin context are kept constant in our isogenic yeast assay. The small molecules BAY11-7082 and ethyl-pyruvate as well as expressed IkBalpha protein acted as NF-kappaB inhibitors in yeast, more strongly towards p65. Thus, the yeast-based system can recapitulate NF-kappaB features found in human cells, thereby providing opportunities to address various NF-kappaB functions, interactions and chemical modulators. PMID- 26147606 TI - Analysis of Nanoporosity in Moisture Permeation Barrier Layers by Electrochemical Impedance Spectroscopy. AB - Water permeation in inorganic moisture permeation barriers occurs through macroscale defects/pinholes and nanopores, the latter with size approaching the water kinetic diameter (0.27 nm). Both permeation paths can be identified by the calcium test, i.e., a time-consuming and expensive optical method for determining the water vapor transmission rate (WVTR) through barrier layers. Recently, we have shown that ellipsometric porosimetry (i.e., a combination of spectroscopic ellipsometry and isothermal adsorption studies) is a valid method to classify and quantify the nanoporosity and correlate it with the WVTR values. Nevertheless, no information is obtained about the macroscale defects or the kinetics of water permeation through the barrier, both essential in assessing the quality of the barrier layer. In this study, electrochemical impedance spectroscopy (EIS) is shown as a sensitive and versatile method to obtain information on nanoporosity and macroscale defects, water permeation, and diffusivity of moisture barrier layers, complementing the barrier property characterization obtained by means of EP and calcium test. EIS is performed on thin SiO2 barrier layers deposited by plasma enhanced-CVD. It allows the determination of the relative water uptake in the SiO2 layers, found to be in agreement with the nanoporosity content inferred by EP. Furthermore, the kinetics of water permeation is followed by EIS, and the diffusivity (D) is determined and found to be in accordance with literature values. Moreover, differently from EP, EIS data are shown to be sensitive to the presence of local macrodefects, correlated with the barrier failure during the calcium test. PMID- 26147607 TI - Radioactive Iodine Therapy Did Not Significantly Increase the Incidence and Recurrence of Subsequent Breast Cancer. AB - CONTEXT: Previous studies on the extent to which radioactive iodine (RAI) therapy for thyroid cancer increases the risk of subsequently developing breast cancer have given conflicting results. OBJECTIVE: This study aimed to evaluate the effect of RAI treatment on breast cancer development and recurrence among female patients with primary thyroid cancer. DESIGN: This was a retrospective cohort study. The risk of subsequent breast cancer associated with RAI and its dose in hazard ratios (HRs) with 95% confidential intervals (CIs) were calculated using time-dependent Cox proportional hazard models. PATIENTS: A total of 6150 patients with thyroid cancer enrolled between 1973 and 2009 were followed until December 2012. Of these, 3631 (59.0%) received RAI therapy. During the follow-up period, 99 primary breast cancers were diagnosed. MAIN OUTCOME MEASURE: Risk of breast cancer development according to RAI therapy and RAI dose during treatment for primary thyroid cancer. RESULTS: RAI therapy did not significantly increase the incidence of subsequent breast cancer among female patients (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.22-1.06) when a 2-year latency period was accounted for. High-dose RAI (>=120 mCi) was associated with a reduced incidence of subsequent breast cancer (HR, 0.17; 95% CI, 0.05-0.62) in the cohort with a 2 year latency period. CONCLUSIONS: The long-term follow-up results of this study suggest that RAI treatment for patients with thyroid cancer may not increase the risk or recurrence of breast cancer. PMID- 26147608 TI - Abnormal Responsiveness to Dexamethasone-Suppressed CRH Test in Patients With Bilateral Adrenal Incidentalomas. AB - CONTEXT: The bilateral formation of nodules indicates that the pathogenesis of bilateral adrenal incidentalomas (AI) may differ from that of unilateral AI. A possible role of hypothalamo-pituitary-adrenal (HPA) axis dysregulation in their formation has not been investigated. OBJECTIVE: The objective of the study was to evaluate the presence of altered feedback regulation of HPA axis in patients with bilateral AI. DESIGN: The dexamethasone (DEX) suppression-CRH test was used to assess ACTH and cortisol responses in controls and patients with unilateral and bilateral AI. SETTING: The study was conducted at endocrine departments of two tertiary centers. PATIENTS: We studied 24 controls and 39 patients with unilateral and 46 with bilateral AI. INTERVENTIONS: All subjects underwent standard low-dose dexamethasone suppression followed by iv bolus administration of human CRH (100 MUg). RESULTS: Bilateral AI had higher levels of ACTH and cortisol after the DEX-CRH challenge compared with both controls (P < .01 for ACTH and P < .001 for cortisol) and unilateral AI (P < .01 for ACTH and cortisol). A positive response, defined as peak ACTH greater than 10 pg/mL at 15 and/or 30 minutes followed by a significant rise in cortisol levels, was noted in 41.3% of bilateral vs 2.6% in unilateral AI (P < .001). Bilateral responders did not differ from nonresponders in demographic or hormonal characteristics, but they had larger total adrenal size compared with nonresponders. CONCLUSIONS: A significant proportion of patients with bilateral AI demonstrate positive responses to the DEX-CRH test compared with unilateral AI, providing ground for potential involvement of HPA axis dysregulation in the pathogenesis, in at least a subgroup, of bilateral AI patients. PMID- 26147609 TI - Crooke's Changes In Cushing's Syndrome Depends on Degree of Hypercortisolism and Individual Susceptibility. AB - CONTEXT: Although Crooke's changes in the pituitary corticotrophs were initially described in 1935, the prevalence in which the changes occur in patients with Cushing's syndrome (CS) has not been established. OBJECTIVE: This study aimed to determine the prevalence and assess clinical features associated with the presence or absence of Crooke's changes in a large set of patients with CS. DESIGN: Information from a prospective computer database and retrospective chart review was analyzed. SETTING: The setting was an academic medical center. PATIENTS: Consecutive patients (N = 213) who received surgery with a preoperative diagnosis of Cushing's disease are included. INTERVENTION: The patients received pituitary surgery and specimens obtained underwent pathological analysis. MAIN OUTCOME MEASURE: The presence or absence of Crooke's changes was determined by histopathological analysis of the normal pituitary tissue included with the specimen obtained at surgery. Cortisol production was measured by 24-hour urine cortisol production. RESULTS: Crooke's changes occurred in 144 of 177 patients (81%) with a histologically demonstrated ACTH-staining tumor and in 74% of 213 patients diagnosed with CS who had pituitary surgery. The presence of Crooke's changes correlated with the finding of an ACTH-staining tumor removed at surgery and with the degree of hypercortisolism. Among patients with histologically established ACTH-staining tumors the prevalence of Crooke's changes was particularly high in patients with a 24-h urinary free cortisol (UFC) of at least 4-fold the upper limit of normal, in which 91% of patients had Crooke's changes, compared with 74% of patients whose maximum UFC was less than 4-fold the upper limit of normal (P = .008). CONCLUSIONS: Crooke's changes occur in 75-80% of patients with CS, and depend on the degree of hypercortisolism and individual variability. Almost all patients with UFC at least 4-fold the upper limit of normal have them, whereas with less severe hypercortisolism the expression of Crooke's changes varies from person to person. PMID- 26147610 TI - Is 'age at first drink' a useful concept in alcohol research and prevention? We doubt that. AB - AIM: To address and discuss the weaknesses of age at first drink (AFD) as a concept in alcohol research and prevention. METHODS: Narrative literature review. RESULTS: Varying from one sip to the consumption of several full drinks, and sometimes including the specification of particular conditions (e.g. without parental consent), no exact definition and operationalization of AFD was found. Evidence reveals poor test-retest reliability when the same individuals report their AFD two or more times. Theoretical arguments and empirical evidence fail to explain why having one sip or one drink earlier than peers should cause heavier drinking and related problems later in life. Alternative explanations such as self-selection, third variable effects and systematic report bias are not considered in most studies. These shortcomings also make AFD unsuitable as an indicator or marker of underlying problems such as conduct problems and academic failure. Together with unjustified causal inferences, this has led to an over emphasis on the relevance of postponing AFD as a way to prevent problems later in life. CONCLUSION: We argue in favour of shifting the focus of alcohol research and prevention away from AFD towards a better understanding of the progression from infrequent, low-quantity drinking to more detrimental drinking patterns and the prevention of associated acute and short-term harm. PMID- 26147611 TI - How to Establish and Follow up a Large Prospective Cohort Study in the 21st Century--Lessons from UK COSMOS. AB - Large-scale prospective cohort studies are invaluable in epidemiology, but they are increasingly difficult and costly to establish and follow-up. More efficient methods for recruitment, data collection and follow-up are essential if such studies are to remain feasible with limited public and research funds. Here, we discuss how these challenges were addressed in the UK COSMOS cohort study where fixed budget and limited time frame necessitated new approaches to consent and recruitment between 2009-2012. Web-based e-consent and data collection should be considered in large scale observational studies, as they offer a streamlined experience which benefits both participants and researchers and save costs. Commercial providers of register and marketing data, smartphones, apps, email, social media, and the internet offer innovative possibilities for identifying, recruiting and following up cohorts. Using examples from UK COSMOS, this article sets out the dos and don'ts for today's cohort studies and provides a guide on how best to take advantage of new technologies and innovative methods to simplify logistics and minimise costs. Thus a more streamlined experience to the benefit of both research participants and researchers becomes achievable. PMID- 26147613 TI - Analytic errors in Sysmex-generated hematology results in blood from a dog with chronic lymphocytic leukemia. AB - A blood sample from a 14-year-old dog was submitted to the veterinary diagnostic laboratory of the University of Milan for marked leukocytosis with atypical cells. A diagnosis of chronic T-cell lymphocytic leukemia (CLL) was made based on blood smear evaluation and flow cytometric phenotyping. A CBC by Sysmex XT-2000iV revealed a moderate normocytic normochromic anemia. Red blood cells counted by optic flow cytometry (RBC-O) resulted in a higher value than using electrical impedance (RBC-I). The relative reticulocyte count based on RNA content and size was 35.3%, while the manual reticulocyte count was < 1%. The WBC count of 1,562,680 cells/MUL was accompanied by a flag. Manual counts for RBC and WBC using the Burker chamber confirmed the Sysmex impedance results. Finally the manual PCV was lower than HCT by Sysmex. While Sysmex XT can differentiate between RBC and WBC by impedance, even in the face of extreme lymphocytosis due to CLL, RBC-O can be affected by bias, resulting in falsely increased RBC and reticulocyte numbers. Overestimation of RBC-O may be due to incorrect Sysmex classification of leukemic cells or their fragments as reticulocytes. This phenomenon is known as pseudoreticulocytosis and can lead to misinterpretation of regenerative anemia. On the other side PCV can be affected by bias in CLL due to the trapping of RBC in the buffy coat, resulting in a pink hue in the separation area. As HGB concentration is not affected by flow cytometric or other cell related artifacts it may represent the most reliable variable to assess the degree of anemia in cases of CLL. PMID- 26147612 TI - Persistence of Positive Carryover Effects in the Oyster, Saccostrea glomerata, following Transgenerational Exposure to Ocean Acidification. AB - Ocean acidification (OA) is predicted to have widespread implications for marine organisms, yet the capacity for species to acclimate or adapt over this century remains unknown. Recent transgenerational studies have shown that for some marine species, exposure of adults to OA can facilitate positive carryover effects to their larval and juvenile offspring that help them to survive in acidifying oceanic conditions. But whether these positive carryover effects can persist into adulthood or the next generation is unknown. Here we tested whether positive carryover effects found in larvae of the oyster, Saccostrea glomerata following transgenerational exposure to elevated CO2, could persist into adulthood and whether subsequent transgenerational exposure of adults to elevated CO2 would facilitate similar adaptive responses in the next generation of larvae and juveniles. Following our previous transgenerational exposure of parental adults and first generation (F1) larvae to ambient (385 MUatm) and elevated (856 MUatm) CO2, newly settled F1 juveniles were transferred to the field at ambient CO2 for 14 months, until they reached reproductive maturity. At this time, the F1 adults were returned to the laboratory and the previous transgenerational CO2 exposure was repeated to produce F2 offspring. We found that the capacity of adults to regulate extracellular pH at elevated CO2 was improved if they had a prior history of transgenerational exposure to elevated CO2. In addition, subsequent transgenerational exposure of these adults led to an increase in the resilience of their larval and juvenile offspring. Offspring with a history of transgenerational exposure to elevated CO2 had a lower percentage abnormality, faster development rate, faster shell growth and increased heart rate at elevated CO2 compared with F2 offspring with no prior history of exposure to elevated CO2. Our results suggest that positive carryover effects originating during parental and larval exposure will be important in mediating some of the impacts of OA for later life-history stages and generations. PMID- 26147614 TI - Avoid violence, rioting, and outrage; approach celebration, delight, and strength: Using large text corpora to compute valence, arousal, and the basic emotions. AB - Ever since Aristotle discussed the issue in Book II of his Rhetoric, humans have attempted to identify a set of "basic emotion labels". In this paper we propose an algorithmic method for evaluating sets of basic emotion labels that relies upon computed co-occurrence distances between words in a 12.7-billion-word corpus of unselected text from USENET discussion groups. Our method uses the relationship between human arousal and valence ratings collected for a large list of words, and the co-occurrence similarity between each word and emotion labels. We assess how well the words in each of 12 emotion label sets-proposed by various researchers over the past 118 years-predict the arousal and valence ratings on a test and validation dataset, each consisting of over 5970 items. We also assess how well these emotion labels predict lexical decision residuals (LDRTs), after co-varying out the effects attributable to basic lexical predictors. We then demonstrate a generalization of our method to determine the most predictive "basic" emotion labels from among all of the putative models of basic emotion that we considered. As well as contributing empirical data towards the development of a more rigorous definition of basic emotions, our method makes it possible to derive principled computational estimates of emotionality specifically, of arousal and valence-for all words in the language. PMID- 26147615 TI - Cerebrospinal fluid biomarkers for Alzheimer's disease: current limitations and recent developments. AB - PURPOSE OF REVIEW: To give perspectives on current limitations and recent developments in the field of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD). RECENT FINDINGS: Three CSF biomarkers for the neuropathological hallmarks of Alzheimer's disease, namely total tau (T-tau), phospho-tau (P-tau) and the 42 amino acid form of amyloid beta (Abeta42), reflecting neurodegeneration, neurofibrillary tangles and amyloid/senile plaques, respectively, have been developed, validated and incorporated into new diagnostic criteria for the disease. Thanks to global collaborative research efforts, these have been to a large extent a success story but there are a number of limitations that warrant further research and discussion. First, bias and random variation in biomarker measurements both within and between laboratories remain an issue. Second, current markers only reflect part of the pathology underlying Alzheimer's disease; new markers of synaptic dysfunction, microglial activation and protein aggregates that are frequently seen alongside plaque and tangle pathology are needed. Third, fluid markers do not represent the anatomic location of any pathological change; CSF markers may be complemented with high resolution molecular imaging techniques. SUMMARY: There has been considerable progress in the validation and standardization of assays for CSF T-tau, P-tau and Abeta42. Novel biomarkers for synaptic function, microglial activation and protein accumulations other than tau and Abeta are in development. Future fluid biomarker research should be conducted in close collaboration with molecular imaging specialists. PMID- 26147616 TI - Recent advances in understanding the neurobiology of childhood socioeconomic disadvantage. AB - PURPOSE OF REVIEW: To provide an update of recent research regarding neural mechanisms of socioeconomic disadvantage. RECENT FINDINGS: The studies reviewed provide convincing evidence of the detrimental effects of early adversities on brain structure and function. The effects of socioeconomic disadvantage and related environmental risks, such as childhood adversity and smoking during pregnancy, while affecting distributed networks of brain regions, have decreased prefrontal activity and volume as a common feature. SUMMARY: Recent work suggests that socioeconomic disadvantage and related risk factors may account for a significant proportion of variance in measures of brain structure and function, which may mediate the increased risk of psychopathology. Impaired prefrontal control may be a convergent mechanism underlying early exposure to socioeconomic risk factors in humans. Environmental imaging, that is, the impact which environmental adversity may have on brain structure and function, has only recently moved into the focus of interest. This is surprising because the link to psychopathology has long since been acknowledged and socioeconomic risk factors are modifiable, meaning that understanding their mechanism may point toward prevention and early intervention mechanisms. In future work, the interplay between different environmental risk factors, their potential epigenetic mechanisms, and their interaction with genetic risk should be studied. PMID- 26147617 TI - New insight of functional molecular imaging into the atheroma biology: 18F-NaF and 18F-FDG in symptomatic and asymptomatic carotid plaques after recent CVA. Preliminary results. AB - AIM: The identification of the vulnerable atheroma plaque could allow a more effective treatment of cerebrovascular accident (CVA). Active calcification and inflammation of the carotid atheroma were assessed and compared in symptomatic and asymptomatic plaques by 18F-NaF and 18F-FDG PET/CT. METHODS: Nine patients investigated for recent CVA and no preventive treatment with statins were enrolled. In each patient, at least one atheroma plaque was detected by CT angiogram. In total, 18 plaques were available: 9 symptomatic and 9 asymptomatic. 18F-NaF uptake and 18F-FDG uptake by each plaque were assessed visually and semiquantitatively by calculating target/background ratios (TBRs) and TBR indexes (TBR symptomatic/TBR asymptomatic and 18F-NaF TBR/18F-FDG TBR within each of the 2 clinical groups of plaques). RESULTS: All plaques showed 18F-NaF and 18F-FDG uptake, and semiquantitation showed higher 18F-NaF uptake by 11 of the 18 plaques, 6 symptomatic and 5 asymptomatic. In the symptomatic group, the mean 18F NaF TBR was 2.12 +/- 0.44, and in the asymptomatic group, it was 1.85 +/- 0.46. The 18F-NaF/18F-FDG showed that, overall, 18F-NaF uptake is higher than 18F-FDG. In the symptomatic plaques, the 18F-NaF was higher for the low calcium content and the lowest for the high. CONCLUSION: Active calcification and inflammation are simultaneous processes in the symptomatic and asymptomatic carotid atheroma. However, active calcification seems predominant over inflammation in both groups. In the symptomatic plaques, the highest 18F-NaF uptake does not correspond with the largest calcium content. These patterns open new insights on the role of 18F NaF in the study of calcification and in the identification of the vulnerable carotid atheroma. PMID- 26147618 TI - Clinical Validation of a Peritoneal Dialysis Prescription Model in the PatientOnLine Software. AB - Peritoneal transport characteristics and residual renal function require regular control and subsequent adjustment of the peritoneal dialysis (PD) prescription. Prescription models shall facilitate the prediction of the outcome of such adaptations for a given patient. In the present study, the prescription model implemented in the PatientOnLine software was validated in patients requiring a prescription change. This multicenter, international prospective cohort study with the aim to validate a PD prescription model included patients treated with continuous ambulatory peritoneal dialysis. Patients were examined with the peritoneal function test (PFT) to determine the outcome of their current prescription and the necessity for a prescription change. For these patients, a new prescription was modeled using the PatientOnLine software (Fresenius Medical Care, Bad Homburg, Germany). Two to four weeks after implementation of the new PD regimen, a second PFT was performed. The validation of the prescription model included 54 patients. Predicted and measured peritoneal Kt/V were 1.52 +/- 0.31 and 1.66 +/- 0.35, and total (peritoneal + renal) Kt/V values were 1.96 +/- 0.48 and 2.06 +/- 0.44, respectively. Predicted and measured peritoneal creatinine clearances were 42.9 +/- 8.6 and 43.0 +/- 8.8 L/1.73 m(2)/week and total creatinine clearances were 65.3 +/- 26.0 and 63.3 +/- 21.8 L/1.73 m(2) /week, respectively. The analysis revealed a Pearson's correlation coefficient for peritoneal Kt/V of 0.911 and Lin's concordance coefficient of 0.829. The value of both coefficients was 0.853 for peritoneal creatinine clearance. Predicted and measured daily net ultrafiltration was 0.77 +/- 0.49 and 1.16 +/- 0.63 L/24 h, respectively. Pearson's correlation and Lin's concordance coefficient were 0.518 and 0.402, respectively. Predicted and measured peritoneal glucose absorption was 125.8 +/- 38.8 and 79.9 +/- 30.7 g/24 h, respectively, and Pearson's correlation and Lin's concordance coefficient were 0.914 and 0.477, respectively. With good predictability of peritoneal Kt/V and creatinine clearance, the present model provides support for individual dialysis prescription in clinical practice. Peritoneal glucose absorption and ultrafiltration are less predictable and are likely to be influenced by additional clinical factors to be taken into consideration. PMID- 26147619 TI - Copy number variation at the GL7 locus contributes to grain size diversity in rice. AB - Copy number variants (CNVs) are associated with changes in gene expression levels and contribute to various adaptive traits. Here we show that a CNV at the Grain Length on Chromosome 7 (GL7) locus contributes to grain size diversity in rice (Oryza sativa L.). GL7 encodes a protein homologous to Arabidopsis thaliana LONGIFOLIA proteins, which regulate longitudinal cell elongation. Tandem duplication of a 17.1-kb segment at the GL7 locus leads to upregulation of GL7 and downregulation of its nearby negative regulator, resulting in an increase in grain length and improvement of grain appearance quality. Sequence analysis indicates that allelic variants of GL7 and its negative regulator are associated with grain size diversity and that the CNV at the GL7 locus was selected for and used in breeding. Our work suggests that pyramiding beneficial alleles of GL7 and other yield- and quality-related genes may improve the breeding of elite rice varieties. PMID- 26147620 TI - The OsSPL16-GW7 regulatory module determines grain shape and simultaneously improves rice yield and grain quality. AB - The deployment of heterosis in the form of hybrid rice varieties has boosted grain yield, but grain quality improvement still remains a challenge. Here we show that a quantitative trait locus for rice grain quality, qGW7, reflects allelic variation of GW7, a gene encoding a TONNEAU1-recruiting motif protein with similarity to C-terminal motifs of the human centrosomal protein CAP350. Upregulation of GW7 expression was correlated with the production of more slender grains, as a result of increased cell division in the longitudinal direction and decreased cell division in the transverse direction. OsSPL16 (GW8), an SBP-domain transcription factor that regulates grain width, bound directly to the GW7 promoter and repressed its expression. The presence of a semidominant GW7(TFA) allele from tropical japonica rice was associated with higher grain quality without the yield penalty imposed by the Basmati gw8 allele. Manipulation of the OsSPL16-GW7 module thus represents a new strategy to simultaneously improve rice yield and grain quality. PMID- 26147621 TI - Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency. AB - INTRODUCTION: The pyruvate dehydrogenase (PDH) complex is localized in the mitochondrial matrix catalyzing the irreversible decarboxylation of pyruvate to acetyl-CoA and NADH. For proper complex regulation the E1-alpha subunit functions as an on/off switch regulated by phosphorylation/dephosphorylation. In different cell types one of the four-pyruvate dehydrogenase kinase isoforms (PDHK1-4) can phosphorylate this subunit leading to PDH inactivation. Our previous results with human Embryonic Stem Cells (hESC), suggested that PDHK could be a key regulator in the metabolic profile of pluripotent cells, as it is upregulated in pluripotent stem cells. Therefore, we wondered if metabolic modulation, via inexpensive pharmacological inhibition of PDHK, could impact metabolism and pluripotency. METHODS/RESULTS: In order to assess the importance of the PDH cycle in mouse Embryonic Stem Cells (mESC), we incubated cells with the PDHK inhibitor dichloroacetate (DCA) and observed that in its presence ESC started to differentiate. Changes in mitochondrial function and proliferation potential were also found and protein levels for PDH (both phosphorylated and non phosphorylated) and PDHK1 were monitored. Interestingly, we were also able to describe a possible pathway that involves Hif-1alpha and p53 during DCA-induced loss of pluripotency. Results with ESCs treated with DCA were comparable to those obtained for cells grown without Leukemia Inhibitor Factor (LIF), used in this case as a positive control for differentiation. CONCLUSIONS: DCA negatively affects ESC pluripotency by changing cell metabolism and elements related to the PDH cycle, suggesting that PDHK could function as a possible metabolic gatekeeper in ESC, and may be a good target to modulate metabolism and differentiation. Although further molecular biology-based experiments are required, our data suggests that inactive PDH favors pluripotency and that ESC have similar strategies as cancer cells to maintain a glycolytic profile, by using some of the signaling pathways found in the latter cells. PMID- 26147623 TI - Genetic, ecological and geographic covariables explaining host range and specificity of a microsporidian parasite. AB - Parasites often have a smaller geographic distribution than their hosts. Common garden infection trials can untangle the role that historical contingencies, ecological conditions and the genetic constitution of local host populations play in limiting parasite geographic range; however, infection trials usually overestimate the range of hosts in which a parasite could naturally persist. This study overcomes that problem by using multigeneration, long-term persistence experiments. We study the microsporidian parasite Hamiltosporidium tvaerminnensis in monoclonal populations of Daphnia magna from 43 widely spread sites. The parasite persisted well in hosts collected from its natural geographic range, but demonstrated long-term persistence in only a few host genotypes outside this range. Genetic distance between hosts from the parasite's origin site and newly tested host populations correlated negatively with parasite persistence. Furthermore, the parasite persisted only in host populations from habitats with a high likelihood of drying up in summer, although we excluded environmental variation in our experiments. Together, our results suggest that host genetic factors play the dominant role in explaining the limited geographic range of parasites and that these genetic differences covary with geographic distance and the habitat type the host is adapted to. PMID- 26147622 TI - In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress. AB - African Americans have a disproportionate risk for developing nephropathy. This disparity has been attributed to coding variants (G1 and G2) in apolipoprotein L1 (APOL1); however, there is little functional evidence supporting the role of this protein in renal function. Here, we combined genetics and in vivo modeling to examine the role of apol1 in glomerular development and pronephric filtration and to test the pathogenic potential of APOL1 G1 and G2. Translational suppression or CRISPR/Cas9 genome editing of apol1 in zebrafish embryos results in podocyte loss and glomerular filtration defects. Complementation of apol1 morphants with wild type human APOL1 mRNA rescues these defects. However, the APOL1 G1 risk allele does not ameliorate defects caused by apol1 suppression and the pathogenicity is conferred by the cis effect of both individual variants of the G1 risk haplotype (I384M/S342G). In vivo complementation studies of the G2 risk allele also indicate that the variant is deleterious to protein function. Moreover, APOL1 G2, but not G1, expression alone promotes developmental kidney defects, suggesting a possible dominant-negative effect of the altered protein. In sickle cell disease (SCD) patients, we reported previously a genetic interaction between APOL1 and MYH9. Testing this interaction in vivo by co-suppressing both transcripts yielded no additive effects. However, upon genetic or chemical induction of anemia, we observed a significantly exacerbated nephropathy phenotype. Furthermore, concordant with the genetic interaction observed in SCD patients, APOL1 G2 reduces myh9 expression in vivo, suggesting a possible interaction between the altered APOL1 and myh9. Our data indicate a critical role for APOL1 in renal function that is compromised by nephropathy-risk encoding variants. Moreover, our interaction studies indicate that the MYH9 locus is also relevant to the phenotype in a stressed microenvironment and suggest that consideration of the context-dependent functions of both proteins will be required to develop therapeutic paradigms. PMID- 26147624 TI - Preventive effects of astaxanthin on diethylnitrosamine-induced liver tumorigenesis in C57/BL/KsJ-db/db obese mice. AB - AIM: Obesity and its related metabolic abnormalities, including oxidative stress and adipokine imbalance, are involved in liver carcinogenesis. The aim of the present study was to examine the effects of astaxanthin, a powerful biological antioxidant, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-db/db (db/db) obese mice. METHODS: Male db/db mice were given a single i.p. injection of DEN (25 mg/kg bodyweight) at 2 weeks of age, and, subsequently, from 4 weeks of age, they were fed a diet containing 200 p.p.m. astaxanthin throughout the experiment. RESULTS: Twenty weeks of astaxanthin administration significantly inhibited the development of hepatocellular neoplasms (liver cell adenoma and hepatocellular carcinoma) and the hepatic expression of cyclin D1 mRNA compared with the basal diet group in DEN-treated db/db mice. Astaxanthin administration in DEN-treated experimental mice markedly reduced the derivatives of reactive oxygen metabolites/biological antioxidant potential ratio, which is a serum marker of oxidative stress, while increasing the mRNA expression of the antioxidant enzymes superoxide dismutase 2 and glutathione peroxidase 1 in the liver and white adipose tissue. The serum levels of adiponectin increased after astaxanthin administration in these mice. CONCLUSION: Dietary astaxanthin prevented the development of liver tumorigenesis in obese mice by improving oxidative stress and ameliorating serum adiponectin level. Therefore, astaxanthin may be useful in the chemoprevention of liver tumorigenesis in obese individuals. PMID- 26147625 TI - Communicating Breast Cancer Screening With Young Women: An Experimental Test of Didactic and Narrative Messages Using Video and Infographics. AB - Cancer is one of the leading causes of death around the world. Mortality from breast cancer can be reduced if the cancer is detected early enough. It is important to find effective communication that encourages early detection of breast cancer. This study aimed to measure differences between narrative and didactic communication on breast cancer awareness, knowledge of appropriate diagnostic exams, attitude toward breast self-exam, and intention to screen for breast cancer through a breast self-exam. It further aimed to test whether any differences in outcomes were associated with the format used to deliver the communication: video or infographic. The effects of the communication strategies were tested using an experimental design with a control group and four experimental groups: narrative video, didactic video, narrative infographic, or didactic infographic. A total of 194 Italian-speaking women ages 18-30 years completed questionnaires before and after exposure. Positive increases were found for all outcome variables after exposure to any communication strategy tested. The didactic message delivered in video format had the most positive effect on awareness and knowledge, whereas the narrative video message had the most positive effect on attitude and intention. For both message types, videos had a more positive influence than infographics when communicating breast cancer information for this audience. This was the first study of message effects of breast cancer communication with Italian-speaking young women. Further research is warranted to understand how to maximize communication strategies so that they are the most effective in influencing behaviors and if these results are consistent with other linguistic populations. PMID- 26147626 TI - Contesting modernity: Tobacco use and romanticism among older Dai farmers in Xishuangbanna, China. AB - The majority of research about tobacco use in China focuses on Han Chinese, the main ethnic group comprising over 90 per cent of the population, and a paucity of research exists on ethnic minorities. The present study elucidates tobacco use among the Dai people, an ethnic group in Yunnan Province, Southwest China. The study design consisted of interviews and grounded theory methodology in a symbolic interactionist theoretical framework. The categories of the grounded theory revealed tobacco consumption was weaved in a complex web of meanings: social practices, perceptions of health, and work lives as agriculturalists, situated in Dai cultural and social milieu. An important finding was the stage managing of tobacco as a symbol of 'tradition' versus 'modernity': Through a process of contested modernity, the older men championed long-standing tobacco customs as representative of Dai heritage and thus their own tobacco use as upholding traditions amid encroaching cultural and societal change in China. These findings are important because little is known about Dai people's tobacco use and how they are responding to social change. There are also implications for the development of culturally-appropriate tobacco control strategies. PMID- 26147627 TI - Biological Impact of Recent Guidelines on Parenteral Nutrition in Preterm Infants. AB - OBJECTIVES: Recent guidelines for preterm neonates recommend early initiation of parenteral nutrition (PN) with high protein and relatively high caloric intake. This review considers whether these changes could influence homeostasis in very preterm infants during the first few postnatal weeks. METHODS: This systematic review of relevant literature from searches of PubMed and recent guidelines was reviewed by investigators from several perinatal centers in France. RESULTS: New recommendations for PN could be associated with metabolic acidosis via the increase in the amino acid ion gap, hyperchloremic acidosis, and ammonia acidosis. The introduction of high-intake amino acids soon after birth could induce hypophosphatemia and hypercalcemia, simulating a "repeat feeding-like syndrome" and could be prevented by the early intake of phosphorus, especially in preterm infants born after fetal growth restriction. Early high-dose amino acid infusions are relatively well tolerated in the preterm infant with regard to renal function. Additional studies, however, are warranted to determine markers of protein intolerance and to specify the optimal composition and amount of amino acid solutions. CONCLUSIONS: Optimal PN following new guidelines in very preterm infants, despite their demonstrated benefits on growth, may induce adverse effects on ionic homeostasis. Clinicians should implement appropriate monitoring to prevent and/or correct them. PMID- 26147628 TI - Early Aggressive Nutrition in Premature Infants: Is This the Best Approach? PMID- 26147629 TI - Travelling With Children on Home Parenteral Nutrition. AB - BACKGROUND: Home parenteral nutrition (HPN) is an established therapy in children with intestinal failure. Parenteral nutrition (PN) management allows most paediatric patients to participate in age-appropriate activities; however, HPN may lead to significant restrictions, particularly going on holiday. We aimed to identify sociodemographic and illness-specific variables that influence if and how families with children on HPN travel. METHODS: A standardised questionnaire was sent to all 40 children on HPN within a large tertiary intestinal failure centre in the United Kingdom. Depending on whether the family had/had not been on holiday since their child had started HPN, questions were asked to understand the reasons for not travelling or to gather information about individual travel experiences. RESULTS: A total of 30 children were enrolled, 20 of 30 went at least once on holiday, and 5 of 30 travelled more than once per year, 70% travelled outside Britain. Going on vacation was more common, the longer the child had been on HPN (P = 0.022); hours spent on PN tolerance of enteral feeds or the child's age did not influence travel behaviour; 80% of parents who went on vacation had a good/worthy experience, 95% would travel again. The biggest reported obstacle was the transportation of PN bags. Ten families sacrificed a holiday over fear that it may be difficult to arrange or because of the child's unstable medical condition. CONCLUSIONS: A significant proportion of families chose to go on holiday away from home despite their child being on HPN. The experience is considered good by most. PMID- 26147630 TI - Value of Fecal Calprotectin as a Biomarker for Juvenile Polyps in Children Investigated With Colonoscopy. AB - OBJECTIVES: The clinical presentation of colonic juvenile polyps with abdominal discomfort and occult rectal bleedings make them difficult to recognize. The aim of this study was to report the clinical features of colonic juvenile polyps in children referred to colonoscopy and evaluate fecal calprotectin (FCP) as a screening biomarker for their diagnosis. METHODS: The study included a total of 266 children (range 3.1-19.0 years, median age 15.8 years) investigated with ileocolonoscopy; of whom, 239 (89%) were investigated for inflammatory bowel disease (IBD). FCPs were analyzed as a marker of colonic inflammation, and levels < 50 mg/kg was considered to be negative. RESULTS: Juvenile polyps were detected in 12 (4.5%) children; the remaining 67 (25.2%) had Crohn disease, 57 (21.4%) ulcerative colitis, 5 (1.9%) unclassified IBD, 4 (1.5%) allergic colitis, bleeding source was localized in 6 (2.3%), and 115 (43.2%) had unspecific or normal findings. FCP was available in 203 (76.3%) children before colonoscopy; levels of FCP were higher in children with juvenile polyps (range 28-2287 mg/kg, median 844 mg/kg) compared with those with normal colonoscopies (range < 20-2443 mg/kg, median 130 mg/kg, P < 0.0001), but not compared with those with active IBD (range < 20-7780 mg/kg, median 962 mg/kg, P = 0.6299). FCPs were available in 9 of 12 children after polypectomy, of whom all had their FCP levels significantly reduced (range 0-281 mg/kg, median 49 mg/kg, P < .0001). CONCLUSIONS: Colonic juvenile polyps are frequently found in pediatric patients presenting with hematochezia and elevated FCP levels. Colonic juvenile polyps are difficult to differentiate from pediatric IBD without a colonoscopy. PMID- 26147631 TI - Hepatitis C in Children Co-infected With Human Immunodeficiency Virus. AB - OBJECTIVES: The objective of this systematic review was to summarize evidence regarding hepatitis C in hepatitis C virus/human immunodeficiency virus (HCV/HIV) co-infected children focusing on mother-to-child transmission, clinical and laboratory features, outcome, and therapies. METHODS: A literature search was performed using multiple keywords and standardized terminology in MEDLINE, EMBASE, and Cochrane databases dating back to their inception up to April 1, 2015, using the following terms hepatitis C virus, HIV, and child. RESULTS: Fifty five of 367 publications were selected for inclusion. In co-infected children, HIV impacted all the different aspects of HCV infection. Maternal HIV infection increased the risk of vertical transmission of hepatitis C. Children with HCV/HIV co-infection presented a lower rate of spontaneous clearance of HCV, were more commonly HCV viraemic, and had higher values of alanine aminotransferase when compared with HCV-monoinfected children. No relevant difference was reported between monoinfection and co-infection with regard to clinical findings. Although the data on the outcome of hepatitis C in the context of co-infection were limited, they were highly suggestive of a more severe outcome in terms of fibrosis in co-infected children. No pediatric data were available on the role of antiretroviral therapy as a cofactor of liver injury in HCV/HIV co-infection. The efficacy of pegylated interferon-alpha and ribavirin in children with HCV/HIV co infection was lower than in monoinfected children. CONCLUSIONS: The effect of HIV co-infection on HCV-related disease was clear with most studies indicating that HIV accelerates HCV progression and reduces the efficacy of the available anti HCV therapies. PMID- 26147632 TI - Ethnic identity salience improves recognition memory in Tibetan students via priming. AB - OBJECTIVES: Social identity salience affects group-reference effect in memory. However, limited studies have examined the influence of ethnic identity salience on group-reference effect among minority group people in conditions where the minority group dominates. In the present research, we aim to investigate, in a Tibetan-dominant context, whether the salience of ethnic identity among Tibetan students could display an influence on their group-reference effect via priming method. METHOD: We recruited 50 Tibetan and 62 Han Chinese students from Tibetan University in Lhasa, the capital of Tibet Autonomous Region, where Tibetans were the majority. A month before the experiment, we tested the baseline of ethnic identity salience of both Tibetan and Han Chinese students using the Twenty Statements Test. In the formal experiment, we assessed the effectiveness of priming method first and then conducted a recognition memory test 2 week later via priming approach. RESULTS: The results showed that the ethnic identity both of Tibetan and Han Chinese participants was not salient in the baseline assessment. However, it was successfully induced via priming among Tibetan students. Tibetan students showed a significant group-reference effect in recognition memory task when their ethnic identity was induced via priming. On the contrary, Han Chinese students did not show increased ethnic awareness and superiority of ethnic in-group reference memory after being primed. CONCLUSIONS: Current research provides new evidence for the influence of salience of ethnic identity on group-reference effect, contributing to the application and extension of social identity theory among minority group people. PMID- 26147633 TI - An examination of actor-partner social support effects on HIV-related problems and interpersonal outcomes among a sample of HIV-positive African American dyads. AB - OBJECTIVES: Social support is an important resource that has been associated with better mental and physical health outcomes among HIV-positive people. However, researchers have not adequately explored how social support functions among HIV positive African Americans. The purpose of the current study was to understand whether HIV-related support resources are associated with relational functioning and HIV-related problems among a sample of HIV-infected African American dyads. METHOD: Exactly 34 HIV-infected (i.e., seroconcordant) dyads compromised of HIV positive African American adults and their HIV-positive adult "informal supporters" from 3 Midwestern urban cities completed psychosocial questionnaires and a communication task. Using the actor-partner interdependence model, we analyzed dyadic data to determine whether there were actor and/or partner effects within dyadic relationships on measures of conflict and HIV-related problems, communication about these problems, and health symptoms. RESULTS: We found significant negative relationships between perceived support and HIV-related problems and perceptions of problem inequity within dyads and a positive relationship between perceived support and communication about these problems within dyads. Contrary to our expectations, we found no relationship between social support and HIV symptoms, relational conflict, or perceptions about dyadic partners' HIV-related problems. CONCLUSIONS: Although our study precludes drawing causal conclusions, we found evidence of a relationship between the personal experience of HIV-related problems, communication about these problems, and perceptions of social support among a small sample of HIV-infected African American dyads. These findings suggest the need to consider how support-related communication within HIV-infected dyads might influence and be influenced by problem perceptions. PMID- 26147634 TI - Prenasal thickness to nasal bone length ratio in normal and trisomy 21 fetuses at 11-14 weeks of gestation. AB - OBJECTIVE: To show the feasibility and to create a reference range for prenasal thickness (PT) and for the PT to nasal bone length (NBL) ratio in normal fetuses at 11-14 gestational weeks and to compare the findings to fetuses with trisomy 21. METHOD: PT, NBL and PT/NBL ratio were measured retrospectively in stored two dimensional images of 1155 normal fetuses and 44 fetuses with trisomy 21. Mid sagittal images were acquired at first trimester ultrasound examinations and were selected from our digital database. RESULTS: The PT increased with CRL from 1.0 mm at 45-mm CRL to 1.6 mm at 84-mm CRL. The mean PT/NBL ratio was 0.6 and was not altered by CRL. The mean PT/NBL ratio in fetuses with trisomy 21 was significantly higher than in normal fetuses (p < 0.0001). For a cut-off value of 0.8 the PT/NBL yielded a sensitivity of 86.4% and a specificity of 98.4% for trisomy 21. CONCLUSION: The assessment of PT between 11 and 14 gestational weeks is feasible with high intraclass correlation. The PT to NBL ratio seems to be a promising marker for trisomy 21 in the first trimester and was superior to the isolated contribution of NBL and PT measurements. PMID- 26147635 TI - Clinical and serological efficacy of topical calcineurin inhibitors in oral lichen planus: a prospective randomized controlled trial. AB - Oral lichen planus (OLP) is a T-cell-mediated disease characterized by immune mediated basal cell degeneration releasing interleukins (ILs) such as IL-6 and IL 8 into the circulation. Their serum levels reportedly reflect disease activity. Although many therapeutic options are available, none are curative. We compared the efficacy of tacrolimus 0.1% ointment and pimecrolimus 1% cream in OLP and correlated with serum IL-6 and IL-8 levels before and after treatment. Forty patients with symptomatic OLP were randomized into two groups, to receive either topical tacrolimus 0.1% ointment or pimecrolimus 1% cream (twice daily for 8 weeks). Patients were assessed at 2, 4, 8, and 12 weeks. At each visit, objective improvement in the net clinical score (NCS), drug tolerability, and side effects were evaluated. Serum IL-6 and IL-8 levels were measured at baseline and at eight weeks. Baseline characteristics were comparable between the groups. The mean NCS declined from 10.9 +/- 4.5 and 9.9 +/- 4.6 at baseline to 5.4 +/- 3.5 and 5.3 +/- 4.2 at 12 weeks for tacrolimus and pimecrolimus group, respectively. At each visit, in both groups, the decline in mean NCS from baseline was statistically significant (P < 0.05) and so was the decline in mean serum IL-6 and IL-8 levels pre- and post-treatment. Pimecrolimus 1% cream seems to be as effective as tacrolimus 0.1% ointment. Serum IL-6 and IL-8 may act as markers of disease activity. However, future efforts are needed to objectify the use of serum interleukin levels in the disease severity index. PMID- 26147636 TI - Toxocara canis infection: Unusual trigger of systemic lupus erythematosus. AB - Infection by Toxocara canis can cause systemic vasculitis. We report here a unique case of systemic lupus erythematosus (SLE) triggered by T. canis infection. An 8-year-old girl was treated with albendazole therapy for common toxocariasis, but she developed two weeks later, asthenia, fever, infiltrated maculopapular eruption of the face, peripheral vascular disease with necrosis of the fingers and inflammatory anemia with proteinuria. Anti-nuclear, anti-DNA and anti-Sm antibodies positivity, together with minimal change nephritis with mesangial exclusive IgM deposit on renal biopsy and clinical relapse after initially successful steroid therapy, led to the diagnosis of SLE. T. canis infection can trigger systemic lupus but must also be ruled out of the differential diagnosis given its association with autoimmunity. PMID- 26147637 TI - Sparse canonical correlation analysis from a predictive point of view. AB - Canonical correlation analysis (CCA) describes the associations between two sets of variables by maximizing the correlation between linear combinations of the variables in each dataset. However, in high-dimensional settings where the number of variables exceeds the sample size or when the variables are highly correlated, traditional CCA is no longer appropriate. This paper proposes a method for sparse CCA. Sparse estimation produces linear combinations of only a subset of variables from each dataset, thereby increasing the interpretability of the canonical variates. We consider the CCA problem from a predictive point of view and recast it into a regression framework. By combining an alternating regression approach together with a lasso penalty, we induce sparsity in the canonical vectors. We compare the performance with other sparse CCA techniques in different simulation settings and illustrate its usefulness on a genomic dataset. PMID- 26147638 TI - Down-regulation of prostate stem cell antigen (PSCA) by Slug promotes metastasis in nasopharyngeal carcinoma. AB - Distant metastasis and local recurrence are still the major causes for failure of treatment in patients with nasopharyngeal carcinoma (NPC), making it urgent to further elicit the molecular mechanisms of NPC metastasis. Using a gene microarray including transcription factors and known markers for cancer stem cells, prostate stem cell antigen (PSCA) was found to be significantly down regulated in metastatic NPC in lymph node, compared to its primary tumour, and in NPC cell lines with high metastatic ability compared to those with low metastatic ability. NPC patients with low PSCA expression had a consistently poor metastasis free survival (p = 0.003). Knockdown and overexpression of PSCA respectively enhanced and impaired the migration and invasion in vitro and the lung metastasis in vivo of NPC cells. Mechanistically, the enhancement of NPC metastasis by knocking down PSCA probably involved epithelial-mesenchymal transition (EMT), by up-regulating N-cadherin and ZEB1/2 and by activating RhoA. The down-regulation of PSCA in NPC cells resulted directly from the binding of Slug to the PSCA promoter. PSCA may be a potential diagnostic marker and therapeutic target for patients with NPC. PMID- 26147639 TI - An NIR-triggered and thermally responsive drug delivery platform through DNA/copper sulfide gates. AB - Nanomaterials for effective drug delivery require zero pre-release and on-demand release of therapeutic drugs. In this work we demonstrate a novel drug delivery system composed of a mesoporous silica platform conjugated to CuS nanoparticles with two complementary DNA sequences. CuS nanoparticles act as both gatekeepers preventing pre-release of drugs and photothermal agents for effective killing of cancer cells. This system exhibits temperature and NIR-responsive DOX release, with an additional accelerated release rate with GSH treatment. Therefore, it can act as an effective anticancer drug delivery carrier with triggered drug release and efficient anti-cancer effect in vitro after NIR irradiation. PMID- 26147640 TI - THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection. AB - Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins that may function at early steps of infection in a cell type dependent manner, the mechanism of virus entry is still poorly understood. Using a computational biology approach, correlating gene expression with virus infectivity in 54 cell lines, we identified THY-1 as a putative host determinant for HCMV infection in these cells. With a series of loss-of-function, gain-of function and protein-protein interaction analyses, we found that THY-1 mediates HCMV infection at the entry step and is important for infection that occurs at a low m.o.i. THY-1 antibody that bound to the cell surface blocked HCMV during the initial 60 minutes of infection in a dose-dependent manner. Down-regulation of THY-1 with siRNA impaired infectivity occurred during the initial 60 minutes of inoculation. Both THY-1 antibody and siRNA inhibited HCMV-induced activation of the PI3-K/Akt pathway required for entry. Soluble THY-1 protein blocked HCMV infection during, but not after, virus internalization. Expression of exogenous THY-1 enhanced entry in cells expressing low levels of the protein. THY-1 interacted with HCMV gB and gH and may form a complex important for entry. However, since gB and gH have previously been shown to interact, it is uncertain if THY-1 directly binds to both of these proteins. Prior observations that THY-1 (a) interacts with alphaVbeta3 integrin and recruits paxillin (implicated in HCMV entry), (b) regulates leukocyte extravasation (critical for HCMV viremia), and (c) is expressed on many cells targeted for HCMV infection including epithelial and endothelial cells, fibroblast, and CD34+/CD38- stem cells, all support a role for THY-1 as an HCMV entry mediator in a cell type dependent manner. THY-1 may function through a complex setting, that would include viral gB and gH, and other cellular factors, thus links virus entry with signaling in host cells that ultimately leads to virus infection. PMID- 26147641 TI - Measurement of vascular water transport in human subjects using time-resolved pulsed arterial spin labelling. AB - Most approaches to arterial spin labelling (ASL) data analysis aim to provide a quantitative measure of the cerebral blood flow (CBF). This study, however, focuses on the measurement of the transfer time of blood water through the capillaries to the parenchyma (referred to as the capillary transfer time, CTT) as an alternative parameter to characterise the haemodynamics of the system. The method employed is based on a non-compartmental model, and no measurements need to be added to a common time-resolved ASL experiment. Brownian motion of labelled spins in a potential was described by a one-dimensional general Langevin equation as the starting point, and as a Fokker-Planck differential equation for the averaged distribution of labelled spins at the end point, which takes into account the effects of flow and dispersion of labelled water by the pseudorandom nature of the microvasculature and the transcapillary permeability. Multi inversion time (multi-TI) ASL data were acquired in 14 healthy subjects on two occasions in a test-retest design, using a pulsed ASL sequence and three dimensional gradient and spin echo (3D-GRASE) readout. Based on an error analysis to predict the size of a region of interest (ROI) required to obtain reasonably precise parameter estimates, data were analysed in two relatively large ROIs, i.e. the occipital lobe (OC) and the insular cortex (IC). The average values of CTT in OC were 260 +/- 60 ms in the first experiment and 270 +/- 60 ms in the second experiment. The corresponding IC values were 460 +/- 130 ms and 420 +/- 139 ms, respectively. Information related to the water transfer time may be important for diagnostics and follow-up of cerebral conditions or diseases characterised by a disrupted blood-brain barrier or disturbed capillary blood flow. PMID- 26147642 TI - The Divide Between Breast Density Notification Laws and Evidence-Based Guidelines for Breast Cancer Screening: Legislating Practice. PMID- 26147644 TI - Optical Sectioning and High Resolution in Single-Slice Structured Illumination Microscopy by Thick Slice Blind-SIM Reconstruction. AB - The microscope image of a thick fluorescent sample taken at a given focal plane is plagued by out-of-focus fluorescence and diffraction limited resolution. In this work, we show that a single slice of Structured Illumination Microscopy (two or three beam SIM) data can be processed to provide an image exhibiting tight sectioning and high transverse resolution. Our reconstruction algorithm is adapted from the blind-SIM technique which requires very little knowledge of the illumination patterns. It is thus able to deal with illumination distortions induced by the sample or illumination optics. We named this new algorithm thick slice blind-SIM because it models a three-dimensional sample even though only a single two-dimensional plane of focus was measured. PMID- 26147643 TI - Cofactor-Mediated Conformational Dynamics Promote Product Release From Escherichia coli Dihydrofolate Reductase via an Allosteric Pathway. AB - The enzyme dihydrofolate reductase (DHFR, E) from Escherichia coli is a paradigm for the role of protein dynamics in enzyme catalysis. Previous studies have shown that the enzyme progresses through the kinetic cycle by modulating the dynamic conformational landscape in the presence of substrate dihydrofolate (DHF), product tetrahydrofolate (THF), and cofactor (NADPH or NADP(+)). This study focuses on the quantitative description of the relationship between protein fluctuations and product release, the rate-limiting step of DHFR catalysis. NMR relaxation dispersion measurements of millisecond time scale motions for the E:THF:NADP(+) and E:THF:NADPH complexes of wild-type and the Leu28Phe (L28F) point mutant reveal conformational exchange between an occluded ground state and a low population of a closed state. The backbone structures of the occluded ground states of the wild-type and mutant proteins are very similar, but the rates of exchange with the closed excited states are very different. Integrated analysis of relaxation dispersion data and THF dissociation rates measured by stopped-flow spectroscopy shows that product release can occur by two pathways. The intrinsic pathway consists of spontaneous product dissociation and occurs for all THF-bound complexes of DHFR. The allosteric pathway features cofactor assisted product release from the closed excited state and is utilized only in the E:THF:NADPH complexes. The L28F mutation alters the partitioning between the pathways and results in increased flux through the intrinsic pathway relative to the wild-type enzyme. This repartitioning could represent a general mechanism to explain changes in product release rates in other E. coli DHFR mutants. PMID- 26147645 TI - Effect of Acute Hypercapnia on Outcomes and Predictive Risk Factors for Complications among Patients Receiving Bronchoscopic Interventions under General Anesthesia. AB - BACKGROUND: The aim of this study is to investigate the effect of acute hypercapnia on surgery outcomes among patients receiving bronchoscopic interventions under general anesthesia. Furthermore, independent predictive factors for surgery complications were analyzed. METHOD: A total of 323 patients with airway stenosis were enrolled in this retrospective study. Each patient underwent interventional rigid bronchoscopy under general anesthesia. Arterial blood gas (ABG) was measured intraoperatively. In light of PaCO2 levels in ABG, patients were divided into three groups: Group C (control) (PaCO2:<= 60 mmHg), Group M (moderate) (PaCO2:61-100 mmHg), and Group S (severe) (PaCO2: >100 mmHg). Parameters, including PaO2 levels and recovery delays, were compared across three groups. Complications among patients receiving bronchoscopic interventions were evaluated as well. Independent predictive factors for surgery related complications were analyzed by multivariable regression method. RESULTS: Significant differences in weight (p=0.04), ASA IV (p=0.008), dyspnea index (p=0.003),COPD (p=0.02), dynamic airway collapse (p=0.002), severe stenosis severity (p=0.02), and stenosis locations among three groups were observed. Mild (PaCO2:~60 mmHg) to moderate (PaCO2:60-100 mmHg) hypercapnia was not associated with delayed recovery, whereas severe hypercapnia (PaCO2:>100 mmHg) was associated with delayed recovery, as well as declined PaO2 (p=0.00) and elevated blood glucose levels (p=0.00). The complications of bronchoscopic interventions included postoperative congestive heart failure (14 cases, 4.3%), tracheorrhagia (8 cases, 2.5%), delayed recovery (19 cases, 5.9%), and transfers to ICU after surgery (10 cases, 3.1%). The multivariable regression analysis showed that procedure duration (p=0.003), lobectomy (p=0.007), dynamic airway collapse (p=0.01), severe bronchial stenosis (p=0.01) and hypercapnia (p=0.02) were independent predictive factors for surgery related complications. CONCLUSIONS: Acute hypercapnia lower than 100 mmHg was not associated with detrimental consequences, whereas severe hypercapnia (PaCO2: >100 mmHg) was associated with lower levels of PaO2. Hypercapnia was an independent predictive factor for bronchoscopic intervention complication, which may help physicians to optimize the therapeutic choices. PMID- 26147646 TI - Radiotherapy Compared to Other Strategies in the Treatment of Stage I/II Follicular Lymphoma: A Study of 404 Patients with a Median Follow-Up of 15 Years. AB - PURPOSE: To investigate outcome for patients with follicular lymphoma (FL) stage I-II treated at a population-based referral institution with a median follow-up of 15 years. Overall and cause-specific survival was compared to that of a sex, age and residency matched individuals from normal population. MATERIAL AND METHODS: 404 patients with early stage FL treated between 1980 and 2005 were retrospectively analyzed. Two of three patients had stage I disease. Based on clinical characteristics, first line treatments were radiotherapy (RT) (48% of patients), chemotherapy (CT) (16%), combined chemo-and radiotherapy (CRT) (16%) or observation (OBS) (15%). Survival was modeled with Kaplan-Meier methodology. Multivariate analyses were performed with the Cox model. RESULTS: Fifteen years overall survival (OS), progression free survival (PFS) and time to next treatment (TNT) were 50% (95% confidence interval [CI]: 45-55), 42% (95% CI: 36-47) and 48% (95% CI, 42-54), respectively. For patients treated with RT 97% achieved a complete remission, and 15 year OS, PFS and TNT were 57% (95% CI, 50-64), 46% (95% CI, 39-54) and 49% (95% CI, 42-57), respectively. Relapse rate after RT and CRT was 49% and 36%, respectively. Only 2% of patients who received RT or CRT relapsed inside the radiation field and 5% had isolated near-field relapse. No statistical differences were found between treatment groups regarding death from cardiovascular disease or incidence of second cancer. Compared to a matched normal population, non-lymphoma cancer mortality was higher among patients given RT, hazard ratio 1.66 (95% CI: 1.14-2.42; P<0.01). Compared to other treatment modalities, patients selected for observation without treatment did not have inferior outcome. CONCLUSIONS: A differentiated treatment strategy in early stage FL results in long term survival for the majority of patients. OBS is a valid initial choice for selected patients without lymphoma-related symptoms. PMID- 26147647 TI - Association between Sleep Duration, Insomnia Symptoms and Bone Mineral Density in Older Boston Puerto Rican Adults. AB - OBJECTIVE: To examine the association between sleep patterns (sleep duration and insomnia symptoms) and total and regional bone mineral density (BMD) among older Boston Puerto Rican adults. MATERIALS/METHODS: We conducted a cross-sectional study including 750 Puerto Rican adults, aged 47-79 y living in Massachusetts. BMD at 3 hip sites and the lumbar spine were measured using dual-energy X-ray absorptiometry. Sleep duration (<=5 h, 6 h, 7 h, 8 h, or >=9 h/d) and insomnia symptoms (difficulty initiating sleep, difficulty maintaining sleep, early morning awaking, and non-restorative sleep) were assessed by a questionnaire. Multivariable regression was used to examine sex-specific associations between sleep duration, insomnia symptoms and BMD adjusting for standard confounders and covariates. RESULTS: Men who slept >=9h/d had significantly lower femoral neck BMD, relative to those reporting 8 h/d sleep, after adjusting for age, education level, smoking, physical activity, depressive symptomatology, comorbidity and serum vitamin D concentration. This association was attenuated and lost significance after further adjustment for urinary cortisol and serum inflammation biomarkers. In contrast, the association between sleep duration and BMD was not significant in women. Further, we did not find any significant associations between insomnia symptoms and BMD in men or women. CONCLUSIONS: Our study does not support the hypothesis that shorter sleep duration and insomnia symptoms are associated with lower BMD levels in older adults. However, our results should be interpreted with caution. Future studies with larger sample size, objective assessment of sleep pattern, and prospective design are needed before a conclusion regarding sleep and BMD can be reached. PMID- 26147649 TI - Divergent Synthesis of 2-Aminofurans via Palladium-Catalyzed Acetoxylative, Alkoxylative, and Hydroxylative Cycloisomerization of Homoallenyl Amides. AB - A fine-tunable transformation, including Pd-catalyzed acetoxylative, alkoxylative, and hydroxylative cycloisomerization of homoallenyl amides, has been realized with hypervalent iodine organic compounds as the oxidants, giving polysubstituted 2-aminofurans in promising yields at room temperature. The selective formation of three different types of products from the same starting materials makes this reaction particularly attractive and useful for organic synthesis. PMID- 26147648 TI - Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults. AB - A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development. PMID- 26147650 TI - Multiple rounds of ancient and recent hybridizations have occurred within the Aegilops-Triticum complex. PMID- 26147651 TI - NK Cells of Kidney Transplant Recipients Display an Activated Phenotype that Is Influenced by Immunosuppression and Pathological Staging. AB - To explore phenotype and function of NK cells in kidney transplant recipients, we investigated the peripheral NK cell repertoire, capacity to respond to various stimuli and impact of immunosuppressive drugs on NK cell activity in kidney transplant recipients. CD56dim NK cells of kidney transplanted patients displayed an activated phenotype characterized by significantly decreased surface expression of CD16 (p=0.0003), CD226 (p<0.0001), CD161 (p=0.0139) and simultaneously increased expression of activation markers like HLA-DR (p=0.0011) and CD25 (p=0.0015). Upon in vitro stimulation via Ca++-dependent signals, down modulation of CD16 was associated with induction of interferon (IFN)-gamma expression. CD16 modulation and secretion of NFAT-dependent cytokines such as IFN gamma, TNF-alpha, IL-10 and IL-31 were significantly suppressed by treatment of isolated NK cells with calcineurin inhibitors but not with mTOR inhibitors. In kidney transplant recipients, IFN-gamma production was retained in response to HLA class I-negative target cells and to non-specific stimuli, respectively. However, secretion of other cytokines like IL-13, IL-17, IL-22 and IL-31 was significantly reduced compared to healthy donors. In contrast to suppression of cytokine expression at the transcriptional level, cytotoxin release, i.e. perforin, granzyme A/B, was not affected by immunosuppression in vitro and in vivo in patients as well as in healthy donors. Thus, immunosuppressive treatment affects NK cell function at the level of NFAT-dependent gene expression whereby calcineurin inhibitors primarily impair cytokine secretion while mTOR inhibitors have only marginal effects. Taken together, NK cells may serve as indicators for immunosuppression and may facilitate a personalized adjustment of immunosuppressive medication in kidney transplant recipients. PMID- 26147653 TI - Examination of a Structural Model of Peptidomimicry by Cyclic Acyldepsipeptide Antibiotics in Their Interaction with the ClpP Peptidase. AB - The cyclic acyldepsipeptide (ADEP) antibiotics act by binding the ClpP peptidase and dysregulating its activity. Their exocyclic N-acylphenylalanine is thought to structurally mimic the ClpP-binding, (I/L)GF tripeptide loop of the peptidase's accessory ATPases. We found that ADEP analogues with exocyclic N-acyl tripeptides or dipeptides resembling the (I/L)GF motif were weak ClpP activators and had no bioactivity. In contrast, ADEP analogues possessing difluorophenylalanine N capped with methyl-branched acyl groups-like the side chains of residues in the (I/L)GF motifs-were superior to the parent ADEP with respect to both ClpP activation and bioactivity. We contend that the ADEP's N-acylphenylalanine moiety is not simply a stand-in for the ATPases' (I/L)GF motif; it likely has physicochemical properties that are better suited for ClpP binding. Further, our finding that the methyl-branching on the acyl group of the ADEPs improves activity opens new avenues for optimization. PMID- 26147652 TI - Assessment of cortical and trabecular bone changes in two models of post traumatic osteoarthritis. AB - Subchondral bone is thought to play a significant role in the initiation and progression of the post-traumatic osteoarthritis. The goal of this study was to document changes in tibial and femoral subchondral bone that occur as a result of two lapine models of anterior cruciate ligament injury, a modified ACL transection model and a closed-joint traumatic compressive impact model. Twelve weeks post-injury bones were scanned via micro-computed tomography. The subchondral bone of injured limbs from both models showed decreases in bone volume and bone mineral density. Surgical transection animals showed significant bone changes primarily in the medial hemijoint of femurs and tibias, while significant changes were noted in both the medial and lateral hemijoints of both bones for traumatic impact animals. It is believed that subchondral bone changes in the medial hemijoint were likely caused by compromised soft tissue structures seen in both models. Subchondral bone changes in the lateral hemijoint of traumatic impact animals are thought to be due to transmission of the compressive impact force through the joint. The joint-wide bone changes shown in the traumatic impact model were similar to clinical findings from studies investigating the progression of osteoarthritis in humans. PMID- 26147654 TI - High Amylose White Rice Reduces Post-Prandial Glycemic Response but Not Appetite in Humans. AB - The present study compared the effects of three rice cultivars on postprandial glycemic control and appetite. A single-blind, randomized, crossover clinical trial was performed with 18 healthy subjects, nine males and nine females. Three treatments were administered at three separate study visits: commercially available conventional white rice (short grain), specialty high amylose white rice 1 (Dixiebelle), and specialty high amylose white rice 2 (Rondo). Postprandial capillary blood glucose, venous blood glucose and insulin measurements, and appetite visual analog scale (VAS) surveys were done over the course of two hours. The capillary blood glucose concentrations were significantly lower for Rondo compared to short grain rice at 30 min, and for Dixiebelle and Rondo compared to short grain rice at 45, 60, and 120 min. Capillary blood glucose area under the curve (AUC) was significantly lower for Dixiebelle and Rondo compared to short grain rice. Subjects were significantly more hungry at 30 min after Dixiebelle intake than Rondo intake, but there were no other significant effects in appetite ratings. The present study determined that intake of high amylose rice with resistant starch (RS) can attenuate postprandial blood glucose and insulin response in comparison to short grain rice. PMID- 26147655 TI - Determination of the potential bioavailability of plant microRNAs using a simulated human digestion process. AB - SCOPE: The "dietary xenomiR hypothesis" proposes that microRNAs (miRNAs) in foodstuffs survive transit through the mammalian gastrointestinal tract and pass into cells intact to affect gene regulation. However, debate continues as to whether dietary intake poses a feasible route for such exogenous gene regulators. Understanding on miRNA levels during pretreatments of human diet is essential to test their bioavailability during digestion. This study makes the novel first use of an in vitro method to eliminate the inherent complexities and variability of in vivo approaches used to test this hypothesis. METHODS AND RESULTS: Plant miRNA levels in soybean and rice were measured during storage, processing, cooking, and early digestion using real-time PCR. We have demonstrated for the first time that storage, processing, and cooking does not abolish the plant miRNAs present in the foodstuffs. In addition, utilizing a simulated human digestion system revealed significant plant miRNA bioavailability after early stage digestion for 75 min. Attenuation of plant messenger RNA and synthetic miRNA was observed under these conditions. CONCLUSION: Even after an extensive pretreatment, plant-derived miRNA, delivered by typical dietary ingestion, has a robustness that could make them bioavailable for uptake during early digestion. The potential benefit of these regulatory molecules in pharma nutrition could be explored further. PMID- 26147656 TI - Combinatorial genetic analysis of a network of actin disassembly-promoting factors. AB - The patterning of actin cytoskeleton structures in vivo is a product of spatially and temporally regulated polymer assembly balanced by polymer disassembly. While in recent years our understanding of actin assembly mechanisms has grown immensely, our knowledge of actin disassembly machinery and mechanisms has remained comparatively sparse. Saccharomyces cerevisiae is an ideal system to tackle this problem, both because of its amenabilities to genetic manipulation and live-cell imaging and because only a single gene encodes each of the core disassembly factors: cofilin (COF1), Srv2/CAP (SRV2), Aip1 (AIP1), GMF (GMF1/AIM7), coronin (CRN1), and twinfilin (TWF1). Among these six factors, only the functions of cofilin are essential and have been well defined. Here, we investigated the functions of the nonessential actin disassembly factors by performing genetic and live-cell imaging analyses on a combinatorial set of isogenic single, double, triple, and quadruple mutants in S. cerevisiae. Our results show that each disassembly factor makes an important contribution to cell viability, actin organization, and endocytosis. Further, our data reveal new relationships among these factors, providing insights into how they work together to orchestrate actin turnover. Finally, we observe specific combinations of mutations that are lethal, e.g., srv2Delta aip1Delta and srv2Delta crn1Delta twf1Delta, demonstrating that while cofilin is essential, it is not sufficient in vivo, and that combinations of the other disassembly factors perform vital functions. PMID- 26147657 TI - Role of isocitrate dehydrogenase 1/2 (IDH 1/2) gene mutations in human tumors. AB - In recent years, frequent isocitrate dehydrogenase 1/2 (IDH1/IDH2) gene mutations were found in a variety of tumors, which specifically alter arginine residues of catalytic active site in IDH1/IDH2 and confer new enzymatic function of directly catalyzing alpha-ketoglutarate (alpha-KG) to R-2-hydroxyglutarate (2-HG). 2-HG could competitively inhibit alpha-KG-dependent enzymes and might therefore contribute to tumorigenesis. In addition, mutation status of IDH1/IDH2 is closely related to the progress and prognosis of certain tumors. Thus IDH1/IDH2 is considered to be a promising biomarker for early diagnosis and prognosis and targeted therapy. In this study, the current research on IDH1/IDH2 mutation, especially the mechanisms and clinical characteristics related to tumor, are reviewed. PMID- 26147658 TI - Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease. AB - Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox. PMID- 26147659 TI - Reactions of alpha-diimine-aluminum complexes with sodium alkynides: versatile structures of aluminum sigma-alkynide complexes. AB - Reaction of AlCl(3) with the monoanionic alpha-diimine ligand [NaL] yielded the complex [L(-)Al(III)Cl(2)(-)] (1, L = [(2,6-iPr(2)C(6)H(3))NC(Me)](2)), and subsequent reduction of by sodium metal afforded the mononuclear [L(2-)Al(III)Cl( )(THF)] (2) and binuclear [L(2-)(THF)Al(II)-Al(II)(THF)L(2-)] (3). Compounds 2 and 3 exhibit interesting reactivities to sodium alkynides at room temperature. Treatment of dialumane 3 with 1 equiv. of 4-methylphenylacetylene in the presence of sodium metal yielded the asymmetric Al-Al-bonded compound [Na(Et(2)O)][LAl Al(C[triple bond, length as m-dash]C(C(6)H(4)-Me))L] (4) containing an alkynyl group attached to one of the Al atoms. The reaction of 2 with 4 methylphenylacetylene and Na (or sodium 4-methylphenylacetylide) resulted in the mononuclear product [L(THF)Al(C[triple bond, length as m-dash]C-(C(6)H(4)-Me))] (5) containing a single terminal acetylide ligand. Precursor 2 reacted with 2 equiv. of phenylacetylene (or 4-methylphenylacetylene, trimethylsilylacetylene) and Na to give the tweezer "ate" complexes, [Na(THF)(DME)][LAl(C[triple bond, length as m-dash]CR)(2)] (R = C(6)H(5), ; C(6)H(4)-Me, ; Si(Me)(3), 6c), [Na(THF)](2)[LAl(C[triple bond, length as m-dash]CPh)(2)](2)(MU-C(7)H(8)) (7), [Na(C(7)H(8))][(MU-Na)][LAl(C[triple bond, length as m-dash]CSi(Me)(3))(2)](2) (8), as well as the polymeric [LAl(C[triple bond, length as m-dash]CPh)(2)Na](n) (9). In the products, two alkynyl groups coordinate terminally to one Al center and a sodium ion is embedded between these two alkynyls. Interestingly, both cycloaddition and terminal acetylide coordination of three equiv. of alkyne occurred in the reaction of with 1-hexyne, resulting in the unique dialuminum complex [Na(Et(2)O)](2)[{L(C(C(4)H(9))[double bond, length as m dash]CH)}Al(C[triple bond, length as m-dash]C(C(4)H(9)))(2)](2) (10). Complexes 1 10 have been characterized by NMR ((1)H, (13)C) and IR spectroscopy, elemental analysis, and X-ray diffraction, and their electronic structures were studied by DFT calculations. PMID- 26147660 TI - Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms. AB - Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off-medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non-motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism-based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted. PMID- 26147661 TI - Proteomic Comparison and MRM-Based Comparative Analysis of Metabolites Reveal Metabolic Shift in Human Prostate Cancer Cell Lines. AB - One of the major challenges in prostate cancer therapy remains the development of effective treatments for castration-resistant prostate cancer (CRPC), as the underlying mechanisms for its progression remain elusive. Previous studies showed that androgen receptor (AR) is crucially involved in regulation of metabolism in prostate cancer (PCa) cells throughout the transition from early stage, androgen sensitive PCa to androgen-independent CRPC. AR achieves such metabolic rewiring directively either via its transcriptional activity or via interactions with AMP activated protein kinase (AMPK). However, due to the heterogeneous expression and activity status of AR in PCa cells, it remains a challenge to investigate the links between AR status and metabolic alterations. To this end, we compared the proteomes of three pairs of androgen-sensitive (AS) and androgen-independent (AI) PCa cell lines, namely, PC3-AR(+)/PC3, 22Rv1/Du145, and LNCaP/C42B, using an iTRAQ labeling approach. Our results revealed that most of the differentially expressed proteins between each pair function in metabolism, indicating a metabolic shift between AS and AI cells, as further validated by multiple reaction monitoring (MRM)-based quantification of nucleotides and relative comparison of fatty acids between these cell lines. Furthermore, increased adenylate kinase isoenzyme 1 (AK1) in AS relative to AI cells may result in activation of AMPK, representing a major regulatory factor involved in the observed metabolic shift in PCa cells. PMID- 26147662 TI - Fungal complications after Candida preservation fluid contamination in liver transplant recipients. AB - Donor-derived fungal infections can be associated with severe complications in transplant recipients. Donor-derived candidiasis has been described in kidney transplant recipients where contamination of the preservation fluid (PF) was a commonly proposed source. In liver transplantation, these fungal infections have been less explored. The aim of this study was therefore to determine the incidence and clinical relevance of Candida contamination of preservation fluid in the context of liver transplantation. A 5-year (2008-2012) retrospective multicentre study involving six French liver transplantation centers was performed to determine the incidence of Candida PF contamination. Postoperative clinical features, outcomes in recipients, and risk factors for Candida-related complications of liver transplantation were studied. Candida sp. was isolated from 28 of 2107 preservation fluid samples (1.33%). Candida albicans was the most common yeast (n = 18, 64%). Twenty-two recipients (78.5%) received antifungal therapy (echinocandins in 68%) for 7-37 days. Eight patients developed yeast related complications (28.6%) including hepatic artery aneurysms (n = 6) and Candida peritonitis (n = 2). The 1-year mortality rate among patients after a yeast-related complication was 62.5%. The incidence of Candida PF contamination was low, but was associated with dramatic postoperative complications and high mortality. Close radiological follow-up may enable early recognition of the arterial complications associated with PF contamination by Candida. PMID- 26147663 TI - A Multi-Period Optimization Model for Service Providers Using Online Reservation Systems: An Application to Hotels. AB - This paper presents a multi-period optimization model for high margin and zero salvage products in online distribution channels with classifying customers based on number of products required. Taking hotel customers as an example, one is regular customers who reserve rooms for one day, and the other is long term stay (LTS) customers who reserve rooms for a number of days. LTS may guarantee a specific amount of demand and generate opportunity income for a certain number of periods, meanwhile with risk of punishment incurred by overselling. By developing an operational optimization model and exploring the effects of parameters on optimal decisions, we suggest that service providers should make decisions based on the types of customers, number of products required, and duration of multi period to reduce the loss of reputation and obtain more profit; at the same time, multi-period buying customers should buy products early. Finally, the paper conducts a numerical experiment, and the results are consistent with prevailing situations. PMID- 26147664 TI - Prevalence of hepatitis viruses in patients with acute hepatitis and characterization of the detected genotype 4 hepatitis E virus sequences in Mongolia. AB - Hepatitis E is considered to be a worldwide public health problem. Although the prevalence of hepatitis E virus (HEV) antibodies in healthy individuals is noted to be 11%, no patients with acute hepatitis E have previously been identified in Mongolia. Three hundred two consecutive patients (183 males and 119 females; median age of 22.0 [Interquartile range: 18.3-25.0] years) who were clinically diagnosed with sporadic acute hepatitis during 2012-2013 in Ulaanbaatar, Mongolia, were studied. By serological and/or molecular approaches, 77 (25.5%), 93 (30.8%), 19 (6.3%), 48 (15.9%), and 12 (4.0%) of the patients were diagnosed with acute hepatitis of types A, B, C, D (superinfection of hepatitis delta virus on a background of chronic hepatitis B virus infection) and E, respectively, while the cause of hepatitis was unknown in the remaining 53 patients (17.5%). The 12 hepatitis E patients had no history of travel abroad in the 3 months before the onset of disease, and lived separately in fixed or movable houses with water supplied via pipe, tank or well, denying transmission from a common water supply. The 12 HEV isolates obtained from the patients showed high nucleotide identities of 99.7-100%, and a representative HEV isolate, MNE13-227, was closest to the Chinese isolates of genotype 4, with the highest identity of 97.3% in the 304-nt ORF2 sequence and 92.1% over the entire genome. The present study revealed the occurrence of autochthonous acute hepatitis E in Mongolia, caused by a monophyletic genotype 4 HEV strain. PMID- 26147665 TI - Association of DNA Methylation with Acute Mania and Inflammatory Markers. AB - In order to determine whether epigenetic changes specific to the manic mood state can be detected in peripheral blood samples we assayed DNA methylation levels genome-wide in serum samples obtained from 20 patients hospitalized for mania and 20 unaffected controls using the Illumina 450K methylation arrays. We identified a methylation locus in the CYP11A1 gene, which is regulated by corticotropin, that is hypo-methylated in individuals hospitalized for mania compared with unaffected controls. DNA methylation levels at this locus appear to be state related as levels in follow-up samples collected from mania patients six months after hospitalization were similar to those observed in controls. In addition, we found that methylation levels at the CYP11A1 locus were significantly correlated with three inflammatory markers in serum in acute mania cases but not in unaffected controls. We conclude that mania is associated with alterations in levels of DNA methylation and inflammatory markers. Since epigenetic markers are potentially malleable, a better understanding of the role of epigenetics may lead to new methods for the prevention and treatment of mood disorders. PMID- 26147667 TI - Discounting testimony with the argument ad hominem and a Bayesian congruent prior model. AB - When directed to ignore evidence of a witness's previous bad character because of a violation of the rules of evidence, are jurors' beliefs still affected? The intuition is that they will be because in everyday argumentation, fallacies, like the ad hominem, are effective argumentative strategies. An ad hominem argument (against the person) undermines a conclusion by questioning the character of the proposer. This intuition divides current theories of argumentation. According to pragmadialectical theory (e.g., Van Eemeren & Grootendorst, 2004), procedural rules exactly like the rules of evidence are part of our cognitive resources for evaluating arguments. If one of these rules is violated, an argument should be treated as a fallacy and so it should not alter someone's belief in the conclusion. Some recent experiments investigating how reasonable these arguments are perceived to be seem to support this account (van Eemeren, Garssen, & Meuffels, 2009). These experiments are critiqued from the perspective of the relevance (Walton, 2009, 2010) and epistemic (Hahn & Oaksford, 2006, 2007; Oaksford & Hahn, 2004) approaches to argumentation. An experiment investigates the predictions of these approaches for a graded belief change version of van Eemeren et al.'s (2009) experiment, and the results are modeled using a Bayesian congruent prior model. These results cannot be explained by the pragmadialectical approach and show that in everyday argument people are extremely sensitive to the epistemic relevance of evidence. Moreover, it seems highly unlikely that this can be switched off in more formal contexts such as the courtroom. PMID- 26147666 TI - Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling. AB - Vascular remodelling is a critical vasculopathy found in atheromatous diseases and allograft failures. The local renin angiotensin system (RAS) has been implicated in vascular remodelling. However, the mechanisms by which the augmented local RAS is associated with the initial event of endothelial cell apoptosis in injured vasculature remain undefined. We induced the apoptosis of human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs) through serum starvation (SS). After the cells were subjected to SS, we found that the mRNA expression of angiotensinogen (AGT) was increased by >3-fold in HUVECs and by approximately 2.5-fold in VSMCs. In addition, the expression of angiotensin-converting enzyme (ACE) mRNA was increased in VSMCs but decreased to 50% in HUVECs during the same apoptotic process. Increases in the expression of AGT protein and angiotensin II (Ang II) were found in a serum-free medium conditioned by HUVECs (SSC). The increased Ang II was suppressed using lisinopril (an ACE inhibitor) treatment. Moreover, the activation of ERK1/2 induced by the SSC in VSMCs was also suppressed by losartan. In conclusion, we first demonstrated that the augmented AGT released from apoptotic endothelial cells acts as a vital progenitor of Ang II to accelerate vascular remodelling, and we suggest that blocking local augmented Ang II might be an effective strategy for restraining intimal hyperplasia. PMID- 26147668 TI - Here's looking at you: Visual similarity exacerbates the Moses illusion for semantically similar celebrities. AB - When people read questions like "How many animals of each kind did Moses take on the ark?", many mistakenly answer "2" despite knowing that Noah sailed the ark. This "Moses illusion" occurs when names share semantic features. Two experiments examined whether shared visual concepts (facial features) exacerbate Moses illusions for celebrity names. Questions contained an unrelated distractor name or a semantic distractor name that was visually similar or dissimilar to the correct target name. Both experiments revealed more Moses illusions occurred for questions containing a visually similar semantic distractor compared with either visually dissimilar or unrelated distractors. Furthermore, presenting a picture of the target (Experiment 1) or the visually similar distractor (Experiment 2) before the question increased accurate detection of the illusion, independent of distractor type. Results challenge theoretical explanations of the Moses illusion as resulting from purely shallow semantic processing and demonstrate the importance of visual information in processing proper names, even when presented in written form. (PsycINFO Database Record PMID- 26147669 TI - Strategy use and strategy choice in fraction magnitude comparison. AB - We examined, on a trial-by-trial basis, fraction magnitude comparison strategies of adults with more and less mathematical knowledge. College students with high mathematical proficiency used a large variety of strategies that were well tailored to the characteristics of the problems and that were guaranteed to yield correct performance if executed correctly. Students with less mathematical proficiency sometimes used strategies similar to those of the mathematically proficient students, but often used flawed strategies that yielded inaccurate performance. As predicted by overlapping waves theory, increases in accuracy and speed were related to differences in strategy use, strategy choice, and strategy execution. When asked to choose the best strategy from among 3 possibilities-the strategy the student originally used, a correct alternative, and an incorrect alternative-students with lower fraction knowledge rarely switched from an original incorrect strategy to a correct alternative. This finding suggests that use of poor fraction magnitude comparison strategies stems in large part from lack of conceptual understanding of the requirements of effective strategies, rather than difficulty recalling or generating such strategies. (PsycINFO Database Record PMID- 26147670 TI - The continued influence of implied and explicitly stated misinformation in news reports. AB - The piecemeal reporting of unfolding news events can lead to the reporting of mistaken information (or misinformation) about the cause of the newsworthy event, which later needs to be corrected. Studies of the continued influence effect have shown, however, that corrections are not entirely effective in reversing the effects of initial misinformation. Instead, participants continue to rely on the discredited misinformation when asked to draw inferences and make judgments about the news story. Most prior studies have employed misinformation that explicitly states the likely cause of an outcome. However, news stories do not always provide misinformation explicitly, but instead merely imply that something or someone might be the cause of an adverse outcome. Two experiments employing both direct and indirect measures of misinformation reliance were conducted to assess whether implied misinformation is more resistant to correction than explicitly stated misinformation. The results supported this prediction. Experiment 1 showed that corrections reduced misinformation reliance in both the explicit and implied conditions, but the correction was much less effective following implied misinformation. Experiment 2 showed that implied misinformation was more resistant to correction than explicit misinformation, even when the correction was paired with an alternative explanation. Finally, Experiment 3 showed that greater resistance to correction in the implied misinformation condition did not reflect greater disbelief in the correction. Potential reasons why implied misinformation is more difficult to correct than explicitly provided misinformation are discussed. (PsycINFO Database Record PMID- 26147671 TI - Syncytial giant cell hepatitis in a patient with chronic lymphocytic leukemia. AB - While it commonly occurs in the pediatric population, syncytial giant cell hepatitis is rare in adults, which is diagnosed histologically by the presence of multinucleated cells in the liver. The literature has recorded only approximately one hundred cases in adults during the past two decades in whom malignancy is rarely associated with giant cell hepatitis. Our patient is a 66-year-old woman who was diagnosed with chronic lymphocytic leukemia (CLL) and subsequently developed syncytial giant cell hepatitis. This disease is usually linked to virus infection, autoimmune diseases, and drug medications. The association between CLL and giant cell hepatitis is rare, with only three cases reported. In most cases viral particles on electron microscopy are reported and the patients usually have a history of chemotherapy and hypogammaglobulinemia. Unlike such cases, our patient developed giant cell hepatitis in the absence of such confounding variables. The treatment for our patient was a high-dose corticosteroid and rituxan, with improvement in liver enzymes. PMID- 26147672 TI - Association between Adult Stature and Energy Expenditure in Low-Income Women from Northeastern Brazil. AB - BACKGROUND: Perinatal undernutrition may lead to important metabolic adaptations in adult life, short stature being the most visible. The present study aimed to evaluate the association between stature and total energy expenditure of low income women. METHOD: Women aged 19-45 years from low-income communities in Maceio-AL were recruited. A sample of 67 volunteers was selected and divided into either short stature (<= 152.4 cm; n = 34) or non-short stature (>= 158.7 cm; n = 33) group. Data on socioeconomic status, anthropometric variables, and hormonal profiles was collected. Total energy expenditure and body composition were assessed by the doubly labeled water technique with multiple points over 14 days. In addition, physical activity levels were measured with triaxial accelerometers and dietary intake data were collected using three 24-hour food records. RESULTS: The mean subject age was 30.94 years. Women of short stature had lower body weight and lean body mass compared to non-short women, but there were no differences in thyroid hormone concentrations or daily energy intake between the two groups. Short-stature women showed lower total energy expenditure (P = 0.01) and a significantly higher physical activity level (P = 0.01) compared to non short women. However, the difference in total energy expenditure was no longer significant after statistical adjustment for age, lean body mass, and triiodothyronine concentrations. CONCLUSION: Women with short stature present the same energy intake, but lower total energy expenditure than non-short women, even with a higher physical activity level, which suggests that they are more prone to weight gain. PMID- 26147674 TI - Facile Enhancement in CO-Tolerance of a Polymer-Coated Pt Electrocatalyst Supported on Carbon Black: Comparison between Vulcan and Ketjenblack. AB - The CO poisoning and low durability of the anode platinum electrocatalyst in the direct methanol fuel cell (DMFC) are the two crucial obstacles of the wide commercialization of the DMFC. In this study, we synthesized two different electrocatalysts using VulcanXC-72R (VC) and Ketjenblack (KB) as the carbon supporting material for the methanol oxidation reaction (MOR) and long-term durability test, in which the carbon supporting materials were wrapped by poly[2,2'-(2,6-pyridine)-5,5'-bibenzimidazole] (PyPBI) before the platinum deposition and the fabricated electrocatalysts were coated by the poly(vinylphosphonic acid) (PVPA) via the base-acid reaction. We have found that the as-prepared KB/PyPBI/Pt/PVPA shows a higher durability (7% loss in ECSA) under the potential cycling from 1.0 to 1.5 V vs. RHE compared to that of the VC/PyPBI/Pt/PVPA, which showed a 20% loss in ECSA after 10 000 cycle-durability test. Meanwhile, the KB/PyPBI/Pt/PVPA shows a higher CO tolerance before and after the durability test compared to that of the VC/PyPBI/Pt/PVPA, especially under very high methanol concentration (4 M and 8 M), which is close to the practical application of the DMFC. The observed higher CO tolerance is due to the higher amount of the PVPA (14.6 wt %) in the KB/PyPBI/Pt/PVPA caused by the higher specific surface area of the KB (1232 m(2)/g) compared to the VC (235 m(2)/g). PMID- 26147673 TI - Preconditioning L6 Muscle Cells with Naringin Ameliorates Oxidative Stress and Increases Glucose Uptake. AB - Enhanced oxidative stress contributes to pathological changes in diabetes and its complications. Thus, strategies to reduce oxidative stress may alleviate these pathogenic processes. Herein, we have investigated Naringin mediated regulation of glutathione (GSH) & intracellular free radical levels and modulation of glucose uptake under oxidative stress in L6 cell lines. The results from the study demonstrated a marked decrease in glutathione with a subsequent increase in free radical levels, which was reversed by the pretreatment of Naringin. We also observed that the increased malondialdehyde level, the marker of lipid peroxidation on induction of oxidative stress was retrieved on Naringin pretreatment. Addition of Naringin (100 MUM) showed approximately 40% reduction in protein glycation in vitro. Furthermore, we observed a twofold increase in uptake of fluorescent labeled glucose namely 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4 yl)Amino)-2-Deoxyglucose (2-NBDG) on Naringin treatment in differentiated L6 myoblast. The increased uptake of 2-NBDG by L6 myotubes may be attributed due to the enhanced translocation of GLUT4. Our results demonstrate that Naringin activate GSH synthesis through a novel antioxidant defense mechanism against excessive Reactive Oxygen Species (ROS) production, contributing to the prevention of oxidative damage in addition to its effect on glycemic control. PMID- 26147675 TI - Common Variants in LRP2 and COMT Genes Affect the Susceptibility of Gout in a Chinese Population. AB - Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI >= 25 (P = 0.009). In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A) decreased the risk of gout (OR = 0.77, P = 0.015), whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020). The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI >= 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians. PMID- 26147676 TI - Regulatory T cells and minimal change nephropathy: in the midst of a complex network. AB - Minimal change nephrosis (MCN) is an important cause of morbidity in children. In spite of successful therapies having been developed in the last three decades, most aspects related to pathogenesis still remain poorly defined. Evolution in basic immunology and results deriving from animal models of the disease suggest a complex interaction of factors and cells starting from activation of innate immunity and continuing with antigen presentation. Oxidants, CD80 and CD40/CD40L have probably a relevant role at the start. Studies in animal models and in human beings also suggest the possibility that the same molecules (i.e. CD80, CD40) are expressed by podocytes under inflammatory stimuli, representing a direct potential mechanism for proteinuria. B and T cells could play a relevant role this contest. Implication of B cells is suggested indirectly by studies utilizing anti-CD20 monoclonal antibodies as the main therapy. The role of regulatory T cells (Tregs ) is supported mainly by results in animal models of nephrotic syndrome (i.e. adriamycin, puromycin, lipopolysaccharide), showing a protective effect of direct Treg infusion or stimulation by interleukin 2 (IL-2). Limited studies have also shown reduced amounts of circulating Tregs in patients with active MCN cells. The route from bench to bedside would be reduced if results from animal models were confirmed in human pathology. The expansion of Tregs with recombinant IL-2 and new anti-CD20 monoclonal antibodies is the beginning. Blocking antigen-presenting cells with cytotoxic T lymphocyte antigen (CTLA-4)-Ig fusion molecules inhibiting CD80 and/or with blockers of CD40-CD40 ligand interaction represent potential new approaches. The hope is that evolution in therapies of MCN could fill a gap lasting 30 years. PMID- 26147677 TI - Novel Polymorphic Microsatellite Markers Reveal Genetic Differentiation between Two Sympatric Types of Galaxea fascicularis. AB - The reef-building, scleractinian coral, Galaxea fascicularis, is classified into soft and hard types, based on nematocyst morphology. This character is correlated with the length of the mitochondrial non-coding region (mt-Long: soft colony type, and nematocysts with wide capsules and long shafts; mt-Short: hard colony type, and nematocysts with thin capsules and short shafts). We isolated and characterized novel polymorphic microsatellite markers for G. fascicularis using next-generation sequencing. Based upon the mitochondrial non-coding region, 53 of the 97 colonies collected were mt-Long (mt-L) and 44 were mt-Short (mt-S). Among the 53 mt-L colonies, 27 loci were identified as amplifiable, polymorphic microsatellite loci, devoid of somatic mutations and free of scoring errors. Eleven of those 27 loci were also amplifiable and polymorphic in the 44 mt-S colonies; these 11 are cross-type microsatellite loci. The other 16 loci were considered useful only for mt-L colonies. These 27 loci identified 10 multilocus lineages (MLLs) among the 53 mt-L colonies (NMLL/N = 0.189), and the 11 cross type loci identified 7 MLLs in 44 mt-S colonies (NMLL/N = 0.159). Significant genetic differentiation between the two types was detected based on the genetic differentiation index (FST = 0.080, P = 0.001). Bayesian clustering also indicated that these two types are genetically isolated. While nuclear microsatellite genotypes also showed genetic differentiation between mitochondrial types, the mechanism of divergence is not yet clear. These markers will be useful to estimate genetic diversity, differentiation, and connectivity among populations, and to understand evolutionary processes, including divergence of types in G. fascicularis. PMID- 26147679 TI - Clinical trials for induction of renal allograft tolerance. AB - PURPOSE OF REVIEW: This review summarizes the current state of clinical trials for tolerance induction of human leukocyte antigen-matched or mismatched renal allografts via peritransplant infusion of donor bone marrow-derived products. Recent efforts to apply infusion of expanded regulatory T-cell preparations to minimize immunosuppressive dosages are also reviewed. RECENT FINDINGS: Three centers in the United States have reported clinical trials for tolerance induction in recipients of living donor kidney transplants via donor hematopoietic stem cell transplantation. They have observed varying degrees of successful renal allograft tolerance induction following the establishment of either transient or persistent donor chimerism.A more recent clinical trial planned to evaluate administration of regulatory T cells to harness the immune response has recently been initiated in eight centers in Europe and the United States. SUMMARY: Tolerance induction in clinical kidney transplantation from live donors has been achieved by donor hematopoietic stem cell transplantation. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, as well as to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications. PMID- 26147678 TI - Organ-specific differences in achieving tolerance. AB - PURPOSE OF REVIEW: When it comes to tolerance induction, kidney allografts behave differently from heart allografts that behave differently from lung allografts. Here, we examine how and why different organ allografts respond differently to the same tolerance induction protocol. RECENT FINDINGS: Allograft tolerance has been achieved in experimental and clinical kidney transplantation. Inducing tolerance in experimental recipients of heart and lung allografts has, however, proven to be more challenging. New protocols being developed in nonhuman primates based on mixed chimerism and cotransplantation of tolerogenic organs may provide mechanistic insights to help overcome these challenges. SUMMARY: Tolerance induction protocols that are successful in patients transplanted with 'tolerance prone' organs such as kidneys and livers will most likely not succeed in recipients of 'tolerance-resistant' organs such as hearts and lungs. Separate clinical trials using more robust tolerance protocols will be required to achieve tolerance in heart and lung recipients. PMID- 26147680 TI - Comparison of the Reliability of Acoustic Radiation Force Impulse Imaging and Supersonic Shear Imaging in Measurement of Liver Stiffness. AB - PURPOSE: To compare the reliability of acoustic radiation force impulse (ARFI) imaging and supersonic shear imaging (SSI) in measurement of liver stiffness. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained for all patients. Seventy-nine patients (25 healthy patients, 26 with Child-Pugh class A, and 28 with Child-Pugh class B or C) were enrolled and analyzed from April 2012 to April 2013. In each patient, three abdominal radiologists performed nine measurements of hepatic shear-wave speed with both ARFI imaging and SSI on the same day. Four weeks later, a second session was performed with the same protocol. Interobserver and intraobserver agreements were calculated by using intraclass correlation coefficients. Technical failures and measurement time were evaluated. RESULTS: There were four technical failures in the SSI group and one in the ARFI group (P = .375). The overall interobserver agreement of ARFI imaging was significantly higher than that of SSI (0.941 vs 0.828, P < .001). The overall intraobserver agreement of ARFI imaging was significantly higher than that of SSI (0.915 vs 0.829, P < .001). The overall shear-wave speed measured with SSI was higher than that measured with ARFI imaging (2.04 m/sec +/- 0.88 vs 1.80 m/sec +/- 0.81, P < .001). The measurement time of SSI was longer than that of ARFI imaging (310.8 seconds +/- 88.5 vs 84.5 seconds +/- 15.4, P < .001). CONCLUSION: ARFI imaging was more reliable than SSI in measurement of liver stiffness. The hepatic shear wave speed measured with SSI was higher than that measured with ARFI imaging, which means that the shear-wave speeds measured with ARFI imaging and SSI cannot be used interchangeably. PMID- 26147681 TI - Three-phase bone scintigraphy for diagnosis of Charcot neuropathic osteoarthropathy in the diabetic foot - does quantitative data improve diagnostic value? AB - AIM: To investigate whether inclusion of quantitative data on blood flow distribution compared with visual qualitative evaluation improve the reliability and diagnostic performance of 99 m Tc-hydroxymethylene diphosphate three-phase bone scintigraphy (TPBS) in patients suspected for charcot neuropathic osteoarthropathy (CNO) of the foot. METHOD: A retrospective cohort study of TPBS performed on 148 patients with suspected acute CNO referred from a single specialized diabetes care centre. The quantitative blood flow distribution was calculated based on the method described by Deutsch et al. All scintigraphies were re-evaluated by independent, blinded observers twice with and without quantitative data on blood flow distribution at ankle and focus level, respectively. The diagnostic validity of TPBS was determined by subsequent review of clinical data and radiological examinations. RESULTS: A total of 90 patients (61%) had confirmed diagnosis of CNO. The sensitivity, specificity and accuracy of three-phase bone scintigraphy without/with quantitative data were 89%/88%, 58%/62% and 77%/78%, respectively. The intra-observer agreement improved significantly by adding quantitative data in the evaluation (Kappa value 0.79/0.94). The interobserver agreement was not significantly improved. CONCLUSION: Adding quantitative data on blood flow distribution in the interpretation of TBPS improves intra-observer variation, whereas no difference in interobserver variation was observed. The sensitivity of TPBS in the diagnosis of CNO is high, but holds limited specificity. Diagnostic performance does not improve using quantitative data in the evaluation. This may be due to the reference intervals applied in the study or the absence of a proper gold standard diagnostic procedure for comparison. PMID- 26147682 TI - Impella 5.0 Support in INTERMACS II Cardiogenic Shock Patients Using Right and Left Axillary Artery Access. AB - The catheter-based Impella 5.0 left ventricular assist device (LVAD) is a powerful and less invasive alternative for patients in cardiogenic shock. The use of this device as a primary mechanical circulatory support strategy in INTERMACS II patients should be evaluated. From April 2014 to August 2014, eight Impella 5.0 devices were implanted in seven patients via the axillary artery access (six right and two left). We analyzed the outcome of the four patients in whom the Impella 5.0 device was implanted for the purpose of primary stabilization of cardiogenic shock (INTERMACS II). The remaining three patients had a contraindication for a permanent LVAD and received the device for prolonged weaning from extracorporeal life support (ECLS) system. The implantation of the Impella 5.0 was technically successful in all patients and resulted in the stabilization of the clinical situation. All four patients could be bridged to a long-term device (n = 3) or to cardiac recovery (n = 1). In one patient, 2 days of ECLS support was necessary because of pump thrombosis after 31 days of Impella 5.0 support. One patient with bronchopneumonia had the Impella 5.0 exchanged from the right to the left axillary artery after 22 days of support because of the progressive loss of purge flow and the need for longer bridging to a permanent LVAD. The last patient was supported for giant-cell myocarditis for 22 days and bridged to cardiac recovery. All patients were transferred to the intensive care unit with the Impella device in place. In INTERMACS II situations, the implantation of the Impella 5.0 via the right or left axillary access allowed additional time for decision making. Early patient mobilization, including walking with the Impella device in place, optimized the conditions for either weaning or the implantation of a permanent LVAD. This novel technique of left axillary approach leads to more flexibility in the case of anatomical- or device related contraindications to right-side access, or when the device needs to be exchanged while continuous support is necessary. PMID- 26147683 TI - The transcription factor XBP1 is selectively required for eosinophil differentiation. AB - The transcription factor XBP1 has been linked to the development of highly secretory tissues such as plasma cells and Paneth cells, yet its function in granulocyte maturation has remained unknown. Here we discovered an unexpectedly selective and absolute requirement for XBP1 in eosinophil differentiation without an effect on the survival of basophils or neutrophils. Progenitors of myeloid cells and eosinophils selectively activated the endoribonuclease IRE1alpha and spliced Xbp1 mRNA without inducing parallel endoplasmic reticulum (ER) stress signaling pathways. Without XBP1, nascent eosinophils exhibited massive defects in the post-translational maturation of key granule proteins required for survival, and these unresolvable structural defects fed back to suppress critical aspects of the transcriptional developmental program. Hence, we present evidence that granulocyte subsets can be distinguished by their differential reliance on secretory-pathway homeostasis. PMID- 26147684 TI - Production of IL-10 by CD4(+) regulatory T cells during the resolution of infection promotes the maturation of memory CD8(+) T cells. AB - Memory CD8(+) T cells are critical for host defense upon reexposure to intracellular pathogens. We found that interleukin 10 (IL-10) derived from CD4(+) regulatory T cells (Treg cells) was necessary for the maturation of memory CD8(+) T cells following acute infection with lymphocytic choriomeningitis virus (LCMV). Treg cell-derived IL-10 was most important during the resolution phase, calming inflammation and the activation state of dendritic cells. Adoptive transfer of IL 10-sufficient Treg cells during the resolution phase 'restored' the maturation of memory CD8(+) T cells in IL-10-deficient mice. Our data indicate that Treg cell derived IL-10 is needed to insulate CD8(+) T cells from inflammatory signals, and reveal that the resolution phase of infection is a critical period that influences the quality and function of developing memory CD8(+) T cells. PMID- 26147685 TI - Interferon-gamma regulates cellular metabolism and mRNA translation to potentiate macrophage activation. AB - Interferon-gamma (IFN-gamma) primes macrophages for enhanced microbial killing and inflammatory activation by Toll-like receptors (TLRs), but little is known about the regulation of cell metabolism or mRNA translation during this priming. We found that IFN-gamma regulated the metabolism and mRNA translation of human macrophages by targeting the kinases mTORC1 and MNK, both of which converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of mTORC1 by IFN-gamma was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages showed that IFN-gamma selectively modulated the macrophage translatome to promote inflammation, further reprogram metabolic pathways and modulate protein synthesis. These results show that IFN-gamma-mediated metabolic reprogramming and translational regulation are key components of classical inflammatory macrophage activation. PMID- 26147687 TI - The transcription factor Foxm1 is essential for the quiescence and maintenance of hematopoietic stem cells. AB - Foxm1 is known as a typical proliferation-associated transcription factor. Here we found that Foxm1 was essential for maintenance of the quiescence and self renewal capacity of hematopoietic stem cells (HSCs) in vivo in mice. Reducing expression of FOXM1 also decreased the quiescence of human CD34(+) HSCs and progenitor cells, and its downregulation was associated with a subset of myelodysplastic syndrome (MDS). Mechanistically, Foxm1 directly bound to the promoter region of the gene encoding the receptor Nurr1 (Nr4a2; called 'Nurr1' here), inducing transcription, while forced expression of Nurr1 reversed the loss of quiescence observed in Foxm1-deficient cells in vivo. Thus, our studies reveal a previously unrecognized role for Foxm1 as a critical regulator of the quiescence and self-renewal of HSCs mediated at least in part by control of Nurr1 expression. PMID- 26147686 TI - Inflammation-induced formation of fat-associated lymphoid clusters. AB - Fat-associated lymphoid clusters (FALCs) are a type of lymphoid tissue associated with visceral fat. Here we found that the distribution of FALCs was heterogeneous, with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 cells in the peritoneal cavity through high expression of the chemokine CXCL13, and they supported B cell proliferation and germinal center differentiation during peritoneal immunological challenges. FALC formation was induced by inflammation, which triggered the recruitment of myeloid cells that expressed tumor-necrosis factor (TNF) necessary for signaling via the TNF receptors in stromal cells. Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible formation of FALCs. Thus, FALCs supported and coordinated the activation of innate B cells and T cells during serosal immune responses. PMID- 26147689 TI - Stability of HIV-1 Nucleic Acids in Dried Blood Spot Samples for HIV-1 Drug Resistance Genotyping. AB - Dried blood spots (DBS) are an easy to collect sample-type that can stabilize biological material at ambient temperature for transport and storage, making them ideal for use in resource-limited settings (RLS). We investigated the effect of storage temperature and duration on ability to detect mixed HIV-1 viral RNA populations, and subsequently viral RNA populations in a background of proviral DNA. Part one of the study used DBS samples of whole blood spiked with specific quantities of HIV-1 subtype-B and -C RNA to study mixed virus population detection. Part two used DBS comprising of HIV-1 subtype-B proviral DNA containing U1 cells combined with HIV-1 subtype-C RNA to mimic HIV-1 infected clinical samples as a model system to study the relative stability of HIV-1 RNA and DNA in DBS. Prepared DBS were stored at -20 degrees C and +30 degrees C for periods of one day, one, two, and four weeks. Samples were genotyped to determine changes in the detection of mixtures in the sample over time. From two weeks onwards, storage at +30 degrees C resulted in gradual, time-related reduction in the detection of mixed virus population at log10 VL 4.0 but not at log10 5.0. Proviral DNA and viral RNA were both stable for at least 52 weeks when stored at 20 degrees C, compared to progressive RNA decay over time at +30 degrees C. DBS storage conditions and duration had a significant effect on HIV-1 RNA amplification. Our results demonstrate that DBS storage at ambient temperature (+30 degrees C) should not exceed two weeks, with long-term storage at -20 degrees C or lower. PMID- 26147690 TI - Self-reported skin colour and erythemal sensitivity vs. objectively measured constitutive skin colour in an African population with predominantly dark skin. AB - BACKGROUND: Skin colour is an important factor in skin-related diseases. Accurate determination of skin colour is important for disease prevention and supporting healthy sun behaviour, yet such data are lacking for dark skin types. METHODS: Self-perceived, natural skin colour and sun-skin reaction were compared with objectively measured skin colour among an African population with predominantly dark skin. Unexposed skin of 556 adults (70.1% Black) was measured with a reflectance spectrophotometer to calculate an individual typology angle ( degrees ITA). Participants reported self-perceived skin colour and erythemal sensitivity. RESULTS: There was a strong, positive monotonic correlation between self-reported and measured skin colour (Spearman rho = 0.6438, P < 0.001), but only a weak correlation between self-reported erythemal sensitivity and measured skin colour (Spearman rho = 0.2713, P < 0.001). Self-report biases in underestimation and overestimation of skin colour were evident. Many participants with 'dark brown' and 'black' skin had difficulty in classifying erythemal sensitivity. CONCLUSIONS: In Africa, self-reported skin colour could potentially be used in lieu of spectrophotometer measurements, but options for questions on sunburn and tanning require suitable adjustment. Our study provides evidence of range in degrees ITA values among residents in Africa and reinforces previous results that self-report may be reliable for determining skin colour, but not erythemal sensitivity, for dark skin individuals. PMID- 26147688 TI - Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota. AB - Secretory immunoglobulin A (SIgA) shields the gut epithelium from luminal antigens and contributes to host-microbe symbiosis. However, how antibody responses are regulated to achieve sustained host-microbe interactions is unknown. We found that mice and humans exhibited longitudinal persistence of clonally related B cells in the IgA repertoire despite major changes in the microbiota during antibiotic treatment or infection. Memory B cells recirculated between inductive compartments and were clonally related to plasma cells in gut and mammary glands. Our findings suggest that continuous diversification of memory B cells constitutes a central process for establishing symbiotic host microbe interactions and offer an explanation of how maternal antibodies are optimized throughout life to protect the newborn. PMID- 26147691 TI - Impact of treatment algorithms on the prescribing of antithrombotic therapy in patients with suspected acute coronary syndrome - a prospective audit. AB - AIMS: Chest pain presentations are common although most patients do not have an acute coronary syndrome (ACS). We hypothesized that our local therapeutic guideline was leading to many low risk patients being inappropriately treated with potent anti-thrombotic therapy for ACS. METHODS: We conducted a prospective analysis of patients presenting with suspected ACS to the Western Infirmary Glasgow over a 2 month period between 6/10/13-3/11/13 and 5/4/14-2/5/14. We collated data on demographics, investigation, initial management and final diagnosis. Patients taking warfarin were excluded. We calculated sensitivity, specificity and receiver operating characteristic (ROC) curves for our local guideline, the SIGN guideline and a new guideline proposal. RESULTS: We studied 202 patients of whom 112 (55%) were male with mean (SD) age 60 (15) years. Full anti-thrombotic therapy for ACS was recommended in 91 patients (45%) according to the NHS GG&C guideline, 37 (18%) by the SIGN guideline and 30 (15%) by our new guideline proposal. The final diagnosis was ACS in 39 patients (19%). The current NHS GG&C guideline had a sensitivity of 80%, specificity 63% and AUROC 0.71 (95% CI 0.63, 0.80). The respective values were 62%, 92% and 0.77 (95% CI 0.67, 0.86) for the SIGN guideline and 54%, 94% and 0.74 (95% CI 0.64, 0.84) for our new proposed guideline. CONCLUSIONS: Only one-fifth of patients who present with chest pain or suspected ACS have ACS as their final diagnosis. Our new guideline proposal is highly specific and would minimize unnecessary administration of potent anti-thrombotic therapy to low risk patients. PMID- 26147692 TI - Camelid heavy chain only antibody fragment domain against beta-site of amyloid precursor protein cleaving enzyme 1 inhibits beta-secretase activity in vitro and in vivo. AB - Accumulation and aggregation of the amyloid-beta (Abeta) peptide is associated with Alzheimer's disease (AD). Abeta is generated from the amyloid precursor protein by the successive action of two membrane-associated processing enzymes: beta-secretase or beta-site of amyloid precursor protein cleaving enzyme 1 (BACE1) and gamma-secretase. Inhibition of one or both of these enzymes prevents Abeta generation and the accompanying Abeta accumulation. Antigen binding fragments from camelid heavy chain only antibodies (VHHs) were found to exert excellent enzyme inhibition activity. In the present study, we generated VHHs against BACE1 by active immunization of Lama glama with the recombinant BACE1 protein. Two classes of VHHs were selected from a VHH-phage display library by competitive elution with a peptide encoding the Swedish mutation variant of the BACE1 processing site. One VHH was found to inhibit the enzyme activity of BACE1 in vitro and in cell culture, whereas two other VHHs were found to stimulate BACE1 activity under the same conditions in vitro. Furthermore, an in vivo study with a transgenic AD mouse model, using intracisternal injection of the inhibitory VHH, led to acute reduction of the Abeta load in the blood and brain. This inhibitory VHH may be considered as a candidate molecule for a therapy directed towards reduction of Abeta load and prevention of AD progression. Both the inhibitory and stimulatory VHH may be useful for improving our understanding of the structure-function relationship of BACE1, as well as its role in AD progression. DATABASE: The GenBank sequence accession numbers are KR363186 for VHH B1a; KR363187 for VHH B3a; and KR363188 for VHH B5a. PMID- 26147694 TI - Effects of Long-Term CO2 Enrichment on Soil-Atmosphere CH4 Fluxes and the Spatial Micro-Distribution of Methanotrophic Bacteria. AB - BACKGROUND: Effects of elevated atmospheric CO2 concentrations on plant growth and associated C cycling have intensively been studied, but less is known about effects on the fluxes of radiatively active trace gases other than CO2. Net soil atmosphere CH4 fluxes are determined by the balance of soil microbially-driven methane (CH4) oxidation and methanogenesis, and both might change under elevated CO2. METHODS AND RESULTS: Here, we studied CH4 dynamics in a permanent grassland exposed to elevated CO2 for 14 years. Soil-atmosphere fluxes of CH4 were measured using large static chambers, over a period of four years. The ecosystem was a net sink for atmospheric CH4 for most of the time except summer to fall when net CH4 emissions occurred. We did not detect any elevated CO2 effects on CH4 fluxes, but emissions were difficult to quantify due to their discontinuous nature, most likely because of ebullition from the saturated zone. Potential methanotrophic activity, determined by incubation of fresh sieved soil under standardized conditions, also did not reveal any effect of the CO2 treatment. Finally, we determined the spatial micro-distribution of methanotrophic activity at less than 5* atmospheric (10 ppm) and elevated (10000 ppm) CH4 concentrations, using a novel auto-radiographic technique. These analyses indicated that domains of net CH4 assimilation were distributed throughout the analyzed top 15 cm of soils, with no dependence on CH4 concentration or CO2 treatment. CONCLUSIONS: Our investigations suggest that elevated CO2 exerts no or only minor effects on CH4 fluxes in the type of ecosystem we studied, at least as long as soil moisture differences are small or absent as was the case here. The autoradiographic analyses further indicate that the spatial niche of CH4 oxidation does not shift in response to CO2 enrichment or CH4 concentration, and that the same type of methanotrophs may oxidize CH4 from atmospheric and soil-internal sources. PMID- 26147693 TI - Ethnicity Modifies Associations between Cardiovascular Risk Factors and Disease Severity in Parallel Dutch and Singapore Coronary Cohorts. AB - BACKGROUND: In 2020 the largest number of patients with coronary artery disease (CAD) will be found in Asia. Published epidemiological and clinical reports are overwhelmingly derived from western (White) cohorts and data from Asia are scant. We compared CAD severity and all-cause mortality among 4 of the world's most populous ethnicities: Whites, Chinese, Indians and Malays. METHODS: The UNIted CORoNary cohort (UNICORN) simultaneously enrolled parallel populations of consecutive patients undergoing coronary angiography or intervention for suspected CAD in the Netherlands and Singapore. Using multivariable ordinal regression, we investigated the independent association of ethnicity with CAD severity and interactions between risk factors and ethnicity on CAD severity. Also, we compared all-cause mortality among the ethnic groups using multivariable Cox regression analysis. RESULTS: We included 1,759 White, 685 Chinese, 201 Indian and 224 Malay patients undergoing coronary angiography. We found distinct inter-ethnic differences in cardiovascular risk factors. Furthermore, the associations of gender and diabetes with severity of CAD were significantly stronger in Chinese than Whites. Chinese (OR 1.3 [1.1-1.7], p = 0.008) and Malay (OR 1.9 [1.4-2.6], p<0.001) ethnicity were independently associated with more severe CAD as compared to White ethnicity. Strikingly, when stratified for diabetes status, we found a significant association of all three Asian ethnic groups as compared to White ethnicity with more severe CAD among diabetics, but not in non-diabetics. Crude all-cause mortality did not differ, but when adjusted for covariates mortality was higher in Malays than the other ethnic groups. CONCLUSION: In this population of individuals undergoing coronary angiography, ethnicity is independently associated with the severity of CAD and modifies the strength of association between certain risk factors and CAD severity. Furthermore, mortality differs among ethnic groups. Our data provide insight in inter-ethnic differences in CAD risk factors, CAD severity and mortality. PMID- 26147695 TI - Editorial: Early intervention in response to language delays--is there a danger of putting too many eggs in the wrong basket? PMID- 26147696 TI - Glucagon-like peptide-1 preserves non-alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress-associated pathway. AB - AIM: Glucagon-like peptide-1 (GLP-1) has been increasingly recognized for treating diabetes mellitus, and for its potential to effectively treat non alcoholic fatty liver disease (NAFLD). However, the mechanisms of GLP-1 induction in NAFLD are not completely known. We investigated whether GLP-1 can protect against NAFLD by alleviating endoplasmic reticulum (ER) stress. METHODS: Male Sprague-Dawley rats were fed a high-fat diet and treated with a long-acting GLP-1 receptor agonist, liraglutide. Biochemical, morphological, genetic and protein expression of ER stress were investigated. In vitro, HepG2 cells were exposed to 0.4 mM palmitate fatty acid and treated with different concentrations of GLP-1, and ER protein 46 (ERp46) and ER stress pathways were analyzed. Cellular response to ER stress and apoptosis were determined upon transfection with either ERp46 siRNA or a negative control siRNA. RESULTS: In vivo, the treatment of GLP-1 attenuated the hepatic accumulation of lipids, reduced inflammation and improved metabolic parameters. GLP-1 treatment significantly upregulated the expression of ERp46 and downregulated the ER stress marker. Activation of ER pathways was restrained by GLP-1. Similar observations were made in vitro. Furthermore, inhibition of ERp46 expression by siRNA-mediated silencing increased the ER stress response and enhanced cell apoptosis rates. In addition, GLP-1 could not reduce the levels of ER stress and apoptosis in cells transfected with ERp46 siRNA compared with in negative control transfected cells after palmitate treatment. CONCLUSION: GLP-1 protected against NAFLD by inactivating the ER stress-associated apoptosis pathway. In addition, the effect was possibly related to the signaling pathway of ERp46. PMID- 26147697 TI - Differential Impact of Message Appeals, Food Healthiness, and Poverty Status on Evaluative Responses to Nutrient-Content Claimed Food Advertisements. AB - A 2 * 3 * 2 mixed factorial experimental design was used to examine how three message appeals (benefit-seeking vs. risk-avoidance vs. taste appeals), food healthiness (healthy vs. unhealthy foods), and consumer poverty status (poverty vs. nonpoverty groups) impact evaluative responses to nutrient-content claimed food advertisements. Subjects were partitioned into two groups, those below and those above the poverty line, and exposed to nutrient-content claimed advertisement treatments for healthy and unhealthy foods featuring the three appeals. The findings reaffirmed the interaction effects between perceivably healthy and unhealthy foods and different appeals reported in previous studies, and found interaction effects between consumer poverty level and response to the message appeals featured in the experimental food advertisements. Age, body mass index, current dieting status, education, and gender were examined as covariates. PMID- 26147698 TI - Differential Activation of Human Monocytes and Lymphocytes by Distinct Strains of Trypanosoma cruzi. AB - BACKGROUND: Trypanosoma cruzi strains are currently classified into six discrete typing units (DTUs) named TcI to VI. It is known that these DTUs have different geographical distribution, as well as biological features. TcI and TcII are major DTUs found in patients from northern and southern Latin America, respectively. Our hypothesis is that upon infection of human peripheral blood cells, Y strain (Tc II) and Col cl1.7 (Tc I), cause distinct immunological changes, which might influence the clinical course of Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the infectivity of CFSE-stained trypomastigotes of Col cl1.7 and Y strain in human monocytes for 15 and 72 hours, and determined the immunological profile of lymphocytes and monocytes exposed to the different isolates using multiparameter flow cytometry. Our results showed a similar percentage and intensity of monocyte infection by Y and Col cl1.7. We also observed an increased expression of CD80 and CD86 by monocytes infected with Col cl1.7, but not Y strain. IL-10 was significantly higher in monocytes infected with Col cl1.7, as compared to Y strain. Moreover, infection with Col cl1.7, but not Y strain, led to an increased expression of IL-17 by CD8+ T cells. On the other hand, we observed a positive correlation between the expression of TNF-alpha and granzyme A only after infection with Y strain. CONCLUSION/SIGNIFICANCE: Our study shows that while Col cl1.7 induces higher monocyte activation and, at the same time, production of IL-10, infection with Y strain leads to a lower monocyte activation but higher inflammatory profile. These results show that TcI and TcII have a distinct immunological impact on human cells during early infection, which might influence disease progression. PMID- 26147699 TI - The Efficacy of Intraoperative Neurophysiological Monitoring Using Transcranial Electrically Stimulated Muscle-evoked Potentials (TcE-MsEPs) for Predicting Postoperative Segmental Upper Extremity Motor Paresis After Cervical Laminoplasty. AB - STUDY DESIGN: Prospective study. OBJECTIVE: To investigate the efficacy of transcranial electrically stimulated muscle-evoked potentials (TcE-MsEPs) for predicting postoperative segmental upper extremity palsy following cervical laminoplasty. SUMMARY OF BACKGROUND DATA: Postoperative segmental upper extremity palsy, especially in the deltoid and biceps (so-called C5 palsy), is the most common complication following cervical laminoplasty. Some papers have reported that postoperative C5 palsy cannot be predicted by TcE-MsEPs, although others have reported that it can be predicted. METHODS: This study included 160 consecutive cases that underwent open-door laminoplasty, and TcE-MsEP monitoring was performed in the biceps brachii, triceps brachii, abductor digiti minimi, tibialis anterior, and abductor hallucis. A >50% decrease in the wave amplitude was defined as an alarm point. According to the monitoring alarm, interventions were performed, which include steroid administration, foraminotomies, etc. RESULTS: Postoperative deltoid and biceps palsy occurred in 5 cases. Among the 155 cases without segmental upper extremity palsy, there were no monitoring alarms. Among the 5 deltoid and biceps palsy cases, 3 had significant wave amplitude decreases in the biceps during surgery, and palsy occurred when the patients awoke from anesthesia (acute type). In the other 2 cases in which the palsy occurred 2 days after the operation (delayed type), there were no significant wave decreases. In all of the cases, the palsy was completely resolved within 6 months. DISCUSSION: The majority of C5 palsies have been reported to occur several days after surgery, but some of them have been reported to occur immediately after surgery. Our results demonstrated that TcE-MsEPs can predict the acute type, whereas the delayed type cannot be predicted. CONCLUSIONS: A >50% wave amplitude decrease in the biceps is useful to predict acute-type segmental upper extremity palsy. Further examination about the interventions for monitoring alarm will be essential for preventing palsy. PMID- 26147700 TI - Ocular findings in alopecia areata. AB - Alopecia areata is a T cell mediated disease with which many disorders may be associated. There are few studies reporting ocular findings in alopecia areata. The aim of the study is to assess tear function and ocular surface pathologies in alopecia areata. Thirty-two patients with alopecia areata and 20 age- and sex matched healthy controls were enrolled in the study. Ocular surface disease index questionnaire, Schirmer, tear break-up time, and corneal staining stage tests were done. The data was analyzed using SPSS 10.0 software. One-way variance analysis and Chi-square tests were used as tests of significance. The patient group had significantly higher ocular surface disease index questionnaire and corneal staining stage test scores and lower tear break-up time test scores compared with the control group (P < 0.05). Dry eye disease (DED) was diagnosed in 27 (84%) of 32 alopecia areata patients and in only 3 (15%) of 20 controls, and there was a significant difference between the groups (P < 0.01). T cell mediated autoimmunity has a prominent role in the etiopathogenesis of alopecia areata and dry eye disease. We think that inflammatory mechanisms causing alopecia areata may trigger dry eye disease or vice versa. All patients with AA should be referred to an ophthalmologist for the evaluation of DED and other possible eye pathologies. PMID- 26147701 TI - Use of local visual cues for spatial orientation in terrestrial toads (Rhinella arenarum): The role of distance to a goal. AB - The use of environmental visual cues for navigation is an ability present in many groups of animals. The effect of spatial proximity between a visual cue and a goal on reorientation in an environment has been studied in several vertebrate groups, but never previously in amphibians. In this study, we tested the use of local visual cues (beacons) to orient in an open field in the terrestrial toad (Rhinella arenarum). Experiment 1 showed that toads could orient in space using 2 cues located near the rewarded container. Experiment 2 used only 1 cue placed at different distances to the goal and revealed that learning speed was affected by the proximity to the goal (the closer the cue was to the goal, the faster toads learned its location). Experiment 3 showed that the position of a cue results in a different predictive value. Toads preferred cues located closer to the goal more than those located farther away as a reference for orientation. Present results revealed, for the first time, that (a) toads can learn to orient in an open space using visual cues, and that (b) the effect of spatial proximity between a cue and a goal, a learning phenomenon previously observed in other groups of animals such as mammals, birds, fish, and invertebrates, also affects orientation in amphibians. Thus, our results suggest that toads are able to employ spatial strategies that closely parallel those described in other vertebrate groups, supporting an early evolutionary origin for these spatial orientation skills. PMID- 26147702 TI - The generation effect or simply generating an effect? AB - The Generation Effect is the phenomenon wherein attempting to retrieve or generate information from memory leads to better encoding and retention than passive rehearsal. Kornell and Terrace were the first to provide evidence for the Generation Effect in nonhuman animals, demonstrating that two rhesus monkeys performed markedly worse when tested following a passive learning condition relative to an active learning condition. In Experiment 1, using the same paradigm as Kornell and Terrace, we demonstrate that pigeons also display this effect. However, an assumption underlying the Generation Effect is that, under passive learning conditions, subjects will still display some evidence of learning but less than that displayed in active learning conditions. In Experiment 2, we examined this issue by pretraining pigeons on a list with hints and then comparing their acquisition of that same list to animals that did not receive any pretraining. Again, we found no evidence that pretraining on a list with hints conferred any advantage when learning that list without hints, a manipulation that Kornell and Terrace did not undertake. In summary, our data raise doubts about the evidence for the Generation Effect in nonhuman animals. PMID- 26147703 TI - Focusing and shifting attention in human children (Homo sapiens) and chimpanzees (Pan troglodytes). AB - Humans often must coordinate co-occurring activities, and their flexible skills for doing so would seem to be uniquely powerful. In 2 studies, we compared 4- and 5-year-old children and one of humans' nearest relatives, chimpanzees, in their ability to focus and shift their attention when necessary. The results of Study 1 showed that 4-year-old children and chimpanzees were very similar in their ability to monitor two identical devices and to sequentially switch between the two to collect a reward, and that they were less successful at doing so than 5 year-old children. In Study 2, which required subjects to alternate between two different tasks, one of which had rewards continuously available whereas the other one only occasionally released rewards, no species differences were found. These results suggest that chimpanzees and human children share some fundamental attentional control skills, but that such abilities continue to develop during human ontogeny, resulting in the uniquely human capacity to succeed at complex multitasking. PMID- 26147704 TI - What or where? The meaning of referential human pointing for dogs (Canis familiaris). AB - Dogs have a unique capacity to follow human pointing, and thus it is often assumed that they can comprehend the referential meaning of such signals. However, it is still unclear whether dogs perceive human directional gestures as signals referring to a target object (indicating what to manipulate) or a spatial cue (indicating where to do something). In the present study, we investigated which of these alternative interpretations may explain dogs' responses to human pointing gestures in ostensive communicative and nonostensive cuing contexts. To test whether dogs select the cued object or the cued location, subjects were presented with 2 alternative object-choice trials. An experimenter first attracted the attention of the dog either by calling the dog's name and looking at it (ostensive condition, n = 24) or by clapping the hands (nonostensive condition, n = 24) then pointed at 1 of 2 different toy objects. Subsequently, the experimenter switched the location of the 2 target objects in full view of the dogs by grasping the objects and making a 180 degrees turn. Dogs were then allowed to choose between the 2 objects. In the ostensive condition, dogs showed a significant bias toward the cued location compared with the nonostensive condition in which they performed at chance. These results suggest that pointing refers to a direction or location for dogs, but only if they are addressed with ostensive cues that indicate the communicative intention of the signaler. PMID- 26147705 TI - Spontaneous tempo and rhythmic entrainment in a bonobo (Pan paniscus). AB - The emergence of speech and music in the human species represent major evolutionary transitions that enabled the use of complex, temporally structured acoustic signals to coordinate social interaction. While the fundamental capacity for temporal coordination with complex acoustic signals has been shown in a few distantly related species, the extent to which nonhuman primates exhibit sensitivity to auditory rhythms remains controversial. In Experiment 1, we assessed spontaneous motor tempo and tempo matching in a bonobo (Pan paniscus), in the context of a social drumming interaction. In Experiment 2, the bonobo spontaneously entrained and synchronized her drum strikes within a range around her spontaneous motor tempo. Our results are consistent with the hypothesis that the evolution of acoustic communication builds upon fundamental neurodynamic mechanisms that can be found in a wide range of species, and are recruited for social interactions. PMID- 26147707 TI - Development of a liquid chromatography assay for the determination of opicapone and BIA 9-1079 in rat matrices. AB - Opicapone is a novel potent, reversible and purely peripheral third generation catechol-O-methyltransferase inhibitor, currently under clinical trials as an adjunct to levodopa therapy for Parkinson's disease. To support additional nonclinical pharmacokinetic studies, a novel high-performance liquid chromatographic method coupled to a diode array detector (HPLC-DAD) to quantify opicapone and its active metabolite (BIA 9-1079) in rat plasma and tissues (liver and kidney) is herein reported. The analytes were extracted from rat samples through a deproteinization followed by liquid-liquid extraction. Chromatographic separation was achieved in less than 10 min on a reversed-phase C18 column, applying a gradient elution program with 0.05 M monosodium phosphate solution (pH 2.45 +/- 0.05) and acetonitrile. Calibration curves were linear (r(2) >= 0.994) within the ranges of 0.04-6.0 ug/mL for both analytes in plasma, 0.04-4.0 ug/mL for opicapone in liver and kidney homogenates, and 0.07-4.0 ug/mL and 0.06-4.0 ug/mL for BIA 9-1079 in liver and kidney homogenates, respectively. The overall intra- and inter-day accuracy ranged from -12.68% to 7.70% and the imprecision values did not exceed 11.95%. This new HPLC-DAD assay was also successfully applied to quantify opicapone and BIA 9-1079 in a preliminary pharmacokinetic study. PMID- 26147706 TI - Social conditioned place preference in the captive ground squirrel (Ictidomys tridecemlineatus): Social reward as a natural phenotype. AB - Social behaviors of wild animals are often considered within an ultimate framework of adaptive benefits versus survival risks. By contrast, studies of laboratory animals more typically focus on affective aspects of behavioral decisions, whether a rodent derives a rewarding experience from social encounter, and how this experience might be initiated and maintained by neural circuits. Artificial selection and inbreeding have rendered laboratory animals more affiliative and less aggressive than their wild conspecifics, leaving open the possibility that social reward is an artifact of domestication. We compared social behaviors of wild and captive population of juvenile 13-lined ground squirrels (Ictidomys tridecemlineatus), the latter being 2nd- and 3rd-generation descendants of wild individuals. At an age corresponding to emergence from the burrow, postnatal day (PD) 38, captive squirrels engaged in vigorous social approach and play and these juvenile behaviors declined significantly by PD 56. Similarly, young wild squirrels expressed social proximity and play; affiliative interactions declined with summer's progression and were replaced by agonistic chasing behaviors. Social conditioned place preference testing (conditioned PDs 40-50) indicated that adolescent squirrels derived a rewarding experience from social reunion. Our results support the contention that undomesticated rodents have the capacity for social reward and more generally suggest the possibility that positive affective experiences may support group cohesion, social cooperation, and altruism in the wild. PMID- 26147708 TI - Controllable Coordination Self-Assembly Based on Flexible Tripodal Ligands: From Finite Metallocages to Infinite Polycatenanes Step by Step. AB - This article describes the developments in coordination self-assembly based on flexible tripodal ligands with different metal species. Various finite metallocages such as M3 L2 , M6 L8 , M6 L4 , M4 L4 and different catenanes based on discrete metallocages constructed from flexible tripodal ligands with suitable metal species are presented here. Many M3 L2 metallocages based on ligands L(1) L(12) and different two-coordinated metal species have been prepared, in which various Ag(I) salts and other metal species that have been protected by suitable groups, such as Zn(OAc)2 , ZnBr2 , and PdBr2 , have been used as effective acceptors. All of the M6 L8 -type metallocages are constructed from ligands L(2) or L(12) -L(20) and different four-coordinated metal species, such as various palladium(II) salts or NiCl2 , and have similar topological structures. Only a few discrete M6 L4 -type metallocages, based on ligands L(21) -L(24) , have been reported, using different strategies such as protecting groups and steric hindrance. All of the M4 L4 -type cages have similar topological structures and are constructed from ligands L(25) -L(29) with multiple donor sites. More intriguing interlocking ensembles constructed from discrete metallocages are also described here in detail, namely, three [2]catenanes based on ligands L(30) L(32) and four polycatenanes based on ligands L(33) -L(34) . PMID- 26147709 TI - Massive pericardial effusion due to intrapericardial mixed germ cell tumor in a premature baby. AB - Primary cardiac tumor is uncommon in childhood, with an incidence of 0.06-0.32%, and intrapericardial teratoma represents an exceptional rarity among these entities. Germ cell tumors (GCT) are rare, representing only 1-3% of childhood tumors. Twenty per cent of GCT are malignant and are associated with age and location. Extragonadal involvement accounts for nearly half of the cases. Anterior mediastinum is a common location of malignant germ cell tumors, yet pericardial and aortic adventitia involvement have been rarely reported. Here we report the case of a preterm twin baby boy with intrapericardial mixed germ cell tumor who presented with hydrops fetalis and pericardial effusion. PMID- 26147711 TI - Intranasal Piperine-Loaded Chitosan Nanoparticles as Brain-Targeted Therapy in Alzheimer's Disease: Optimization, Biological Efficacy, and Potential Toxicity. AB - Piperine (PIP) is a phytopharmaceutical with reported neuroprotective potential in Alzheimer's disease (AD). Oral PIP delivery suffers from its hydrophobicity and pre-systemic metabolism. In this article, mono-disperse intranasal chitosan nanoparticles (CS-NPs) were elaborated for brain targeting of PIP. Formula optimization was based on particle size (PS), zeta potential (ZP), polydispersity index (PDI), % entrapment efficiency (% EE), release studies, and transmission electron microscopy. AD was induced in 48 male Wistar rats on which full behavioral and biochemical testing was conducted. Brain toxicity was assessed based on Caspase-3 assay for apoptosis and tumor necrosis factor for inflammation. Spherical NPs with optimum % EE (81.70), PS (248.50 nm), PDI (0.24), and ZP (+56.30 mV) were elaborated. PIP-NPs could significantly improve cognitive functions as efficient as standard drug (donpezil injection) with additional advantages of dual mechanism (Ach esterase inhibition and antioxidant effect). CS-NPs could significantly alleviate PIP nasal irritation and showed no brain toxicity. This work was the first to report additional mechanism of PIP in AD via anti-apoptosis and anti-inflammatory effects. To conclude, mucoadhesive CS NPs were successfully tailored for effective, safe, and non-invasive PIP delivery with 20-folds decrease in oral dose, opening a gate for a future with lower AD morbidity. PMID- 26147710 TI - Physiologically normal 5% O2 supports neuronal differentiation and resistance to inflammatory injury in neural stem cell cultures. AB - Recent studies have demonstrated that neural stem cell (NSC) culture at physiologically normoxic conditions (2-5% O2) is advantageous in terms of neuronal differentiation and survival. Neuronal differentiation is accompanied by a remarkable shift to mitochondrial oxidative metabolism compared with preferentially glycolytic metabolism of proliferating cells. However, metabolic changes induced by growth in a normoxic (5%) O2 culture environment in NSCs have been minimally explored. This study demonstrates that culturing under 5% O2 conditions results in higher levels of mitochondrial oxidative metabolism, decreased glycolysis, and reduced levels of reactive oxygen species in NSC cultures. Inflammation is one of the major environmental factors limiting postinjury NSC neuronal differentiation and survival. Our results show that NSCs differentiated under 5% O2 conditions possess better resistance to in vitro inflammatory injury compared with those exposed to 20% O2. The present work demonstrates that lower, more physiologically normal O2 levels support metabolic changes induced during NSC neuronal differentiation and provide increased resistance to inflammatory injury, thus highlighting O2 tension as an important determinant of cell fate and survival in various stem cell therapies. PMID- 26147712 TI - Substrate-assisted 2D DNA lattices and algorithmic lattices from single-stranded tiles. AB - We present a simple route to circumvent kinetic traps which affect many types of DNA nanostructures in their self-assembly process. Using this method, a new 2D DNA lattice made up of short, single-stranded tile (SST) motifs was created. Previously, the growth of SST DNA assemblies was restricted to 1D (tubes and ribbons) or finite-sized 2D (molecular canvases). By utilizing the substrate assisted growth method, sets of SSTs were designed as unit cells to self-assemble into periodic and aperiodic 2D lattices which continuously grow both along and orthogonal to the helical axis. Notably, large-scale (~1 MUm(2)) fully periodic 2D lattices were fabricated using a minimum of just 2 strand species. Furthermore, the ability to create 2D lattices from a few motifs enables certain rules to be encoded into these SSTs to carry out algorithmic self-assembly. A set of these motifs was designed to execute simple 1-input 1-output COPY and NOT algorithms, the space-time manifestations which were aperiodic 2D algorithmic SST lattices. The methodology presented here can be straightforwardly applied to other motifs which fall into this type of kinetic trap to create novel DNA crystals. PMID- 26147713 TI - Risks of Epilepsy During Pregnancy: How Much Do We Really Know? PMID- 26147714 TI - Processive Incorporation of Deoxynucleoside Triphosphate Analogs by Single Molecule DNA Polymerase I (Klenow Fragment) Nanocircuits. AB - DNA polymerases exhibit a surprising tolerance for analogs of deoxyribonucleoside triphosphates (dNTPs), despite the enzymes' highly evolved mechanisms for the specific recognition and discrimination of native dNTPs. Here, individual DNA polymerase I Klenow fragment (KF) molecules were tethered to a single-walled carbon nanotube field-effect transistor (SWCNT-FET) to investigate accommodation of dNTP analogs with single-molecule resolution. Each base incorporation accompanied a change in current with its duration defined by tauclosed. Under Vmax conditions, the average time of tauclosed was similar for all analog and native dNTPs (0.2 to 0.4 ms), indicating no kinetic impact on this step due to analog structure. Accordingly, the average rates of dNTP analog incorporation were largely determined by durations with no change in current defined by tauopen, which includes molecular recognition of the incoming dNTP. All alpha thio-dNTPs were incorporated more slowly, at 40 to 65% of the rate for the corresponding native dNTPs. During polymerization with 6-Cl-2APTP, 2-thio-dTTP, or 2-thio-dCTP, the nanocircuit uncovered an alternative conformation represented by positive current excursions that does not occur with native dNTPs. A model consistent with these results invokes rotations by the enzyme's O-helix; this motion can test the stability of nascent base pairs using nonhydrophilic interactions and is allosterically coupled to charged residues near the site of SWCNT attachment. This model with two opposing O-helix motions differs from the previous report in which all current excursions were solely attributed to global enzyme closure and covalent-bond formation. The results suggest the enzyme applies a dynamic stability-checking mechanism for each nascent base pair. PMID- 26147715 TI - Validity of diagnostic codes and laboratory measurements to identify patients with idiopathic acute liver injury in a hospital database. AB - PURPOSE: The development and validation of algorithms to identify cases of idiopathic acute liver injury (ALI) are essential to facilitate epidemiologic studies on drug-induced liver injury. The aim of this study is to determine the ability of diagnostic codes and laboratory measurements to identify idiopathic ALI cases. METHODS: In this cross-sectional validation study, patients were selected from the hospital-based Utrecht Patient Oriented Database between 2008 and 2010. Patients were identified using (I) algorithms based on ICD-9-CM codes indicative of idiopathic ALI combined with sets of liver enzyme values (ALT > 2* upper limit of normal (ULN); AST > 1ULN + AP > 1ULN + bilirubin > 1ULN; ALT > 3ULN; ALT > 3ULN + bilirubin > 2ULN; ALT > 10ULN) and (II) algorithms based on solely liver enzyme values (ALT > 3ULN + bilirubin > 2ULN; ALT > 10ULN). Hospital medical records were reviewed to confirm final diagnosis. The positive predictive value (PPV) of each algorithm was calculated. RESULTS: A total of 707 cases of ALI were identified. After medical review 194 (27%) patients had confirmed idiopathic ALI. The PPV for (I) algorithms with an ICD-9-CM code as well as abnormal tests ranged from 32% (13/41) to 48% (43/90) with the highest PPV found with ALT > 2ULN. The PPV for (II) algorithms with liver test abnormalities was maximally 26% (150/571). CONCLUSIONS: The algorithm based on ICD-9-CM codes indicative of ALI combined with abnormal liver-related laboratory tests is the most efficient algorithm for identifying idiopathic ALI cases. However, cases were missed using this algorithm, because not all ALI cases had been assigned the relevant diagnostic codes in daily practice. PMID- 26147717 TI - A tale of two sisters: identical IL36RN mutations and discordant phenotypes. PMID- 26147716 TI - A Unique Human Norovirus Lineage with a Distinct HBGA Binding Interface. AB - Norovirus (NoV) causes epidemic acute gastroenteritis in humans, whereby histo blood group antigens (HBGAs) play an important role in host susceptibility. Each of the two major genogroups (GI and GII) of human NoVs recognizes a unique set of HBGAs through a distinct binding interface that is conserved within a genogroup, indicating a distinct evolutionary path for each genogroup. Here, we characterize a Lewis a (Lea) antigen binding strain (OIF virus) in the GII.21 genotype that does not share the conserved GII binding interface, revealing a new evolution lineage with a distinct HBGA binding interface. Sequence alignment showed that the major residues contributing to the new HBGA binding interface are conserved among most members of the GII.21, as well as a closely related GII.13 genotype. In addition, we found that glycerol inhibits OIF binding to HBGAs, potentially allowing production of cheap antivirals against human NoVs. Taken together, our results reveal a new evolutionary lineage of NoVs selected by HBGAs, a finding that is important for understanding the diversity and widespread nature of NoVs. PMID- 26147718 TI - Synthetic Studies on the Preparation of Alanyl Epoxysulfones as Cathepsin Cysteine Protease Electrophilic Traps. AB - A Darzens reaction between tert-butoxycarbonyl alaninal and chloromethyl phenyl sulfone afforded chlorohydrins, which were converted into epoxysulfones by reaction with sodium tert-butoxide. Epoxysulfone 10 and chloroketone 14 derived from chlorohydrins by oxidation proved to be inhibitors of cathepsins H, S, and C as determined by competitive activity-based protein profiling. PMID- 26147719 TI - Photoreceptors in Chemotrophic Prokaryotes: The Case of Acinetobacter spp. Revisited. AB - A comprehensive description of blue light using flavin (BLUF) photosensory proteins, including preferred domain architectures and the molecular mechanism of their light activation and signal generation, among chemotrophic prokaryotes is presented. Light-regulated physiological responses in Acinetobacter spp. from environmental and clinically relevant strains are discussed. The twitching motility response in A. baylyi sp. ADP1 and the joint involvement of three of the four putative BLUF-domain-containing proteins in this response, in this species, is presented as an example of remarkable photoreceptor redundancy. PMID- 26147720 TI - Efficacy of hyaluronic acid or steroid injections for the treatment of a rat model of rotator cuff injury. AB - This study evaluated dorsal root ganglia from C3-C7, analyzed gait, and compared the expression of calcitonin gene-related peptide (CGRP) which was a marker of inflammatory pain in a rat rotator cuff tear model in which the supraspinatus and infraspinatus tendons were detached; comparisons were made to a sham group in which only the tendons were exposed. Fluorogold was injected into the glenohumeral joint 21 days after surgery in both groups, and saline, steroids, or hyaluronic acid was injected into the glenohumeral joint in the rotator cuff tear group 26 days after surgery. The proportions of CGRP-immunoreactive neurons were higher and the gait parameters were impaired in the rotator cuff tear group compared to in the sham group. However, the CGRP expression was reduced and the gait was improved with steroid or hyaluronic acid injection compared to saline, suggesting that both hyaluronic acid and steroid injections suppressed of inflammation which thought to be provided pain relief. While there were no significant differences, the suppression of CGRP expression and the improved gait after hyaluronic acid and steroid injections suggested that both methods were effective for rat rotator cuff tear model. PMID- 26147721 TI - Microbial Internal Storage Alters the Carbon Transformation in Dynamic Anaerobic Fermentation. AB - Microbial internal storage processes have been demonstrated to occur and play an important role in activated sludge systems under both aerobic and anoxic conditions when operating under dynamic conditions. High-rate anaerobic reactors are often operated at a high volumetric organic loading and a relatively dynamic profile, with large amounts of fermentable substrates. These dynamic operating conditions and high catabolic energy availability might also facilitate the formation of internal storage polymers by anaerobic microorganisms. However, so far information about storage under anaerobic conditions (e.g., anaerobic fermentation) as well as its consideration in anaerobic process modeling (e.g., IWA Anaerobic Digestion Model No. 1, ADM1) is still sparse. In this work, the accumulation of storage polymers during anaerobic fermentation was evaluated by batch experiments using anaerobic methanogenic sludge and based on mass balance analysis of carbon transformation. A new mathematical model was developed to describe microbial storage in anaerobic systems. The model was calibrated and validated by using independent data sets from two different anaerobic systems, with significant storage observed, and effectively simulated in both systems. The inclusion of the new anaerobic storage processes in the developed model allows for more successful simulation of transients due to lower accumulation of volatile fatty acids (correction for the overestimation of volatile fatty acids), which mitigates pH fluctuations. Current models such as the ADM1 cannot effectively simulate these dynamics due to a lack of anaerobic storage mechanisms. PMID- 26147722 TI - Hydrogen Peroxide Scavenging Activity of Novel Coumarins Synthesized Using Different Approaches. AB - New derivatives of 7-hydroxy-4-methylcoumarin were synthesized using a chemical method and a microwave-assisted method to compare the feasibility, reaction times, and yields of the product. The newly synthesized coumarins were characterized by different spectroscopic techniques (FT-IR and NMR) and micro elemental analysis (CHNS). In vitro antioxidant activities of these compounds were evaluated against hydrogen peroxide and were compared with standard natural antioxidant, vitamin C. Our results reveal that these compounds exhibit excellent radical scavenging activities. PMID- 26147723 TI - Involvement of Acidic Amino Acid Residues in Zn(2+) Binding to Respiratory Complex I. AB - Proton transfer across membranes and membrane proteins is a central process in biological systems. Zn(2+) ions are capable of binding to acidic residues, often found within such specific pathways, thereby leading to a blockage. Here we probed Zn(2+) inhibition of the proton-pumping NADH:ubiquinone oxidoreductase from Escherichia coli by means of electrochemically induced FTIR difference spectroscopy. Numerous conformational changes were identified including those that arise from the reorganization of the membrane arm upon electron transfer in the peripheral arm of the protein. Signals at very high wavenumbers (1781 and 1756 cm(-1)) point to the perturbation of acidic residues in a highly hydrophobic environment upon Zn(2+) binding. In variant D563N(L), which lacks part of the proton pumping activity (residue located on the horizontal amphipathic helix), the spectral signature of Zn(2+) binding is changed. Our data support a role for this residue in proton translocation. PMID- 26147724 TI - Ac2-26 Mimetic Peptide of Annexin A1 Inhibits Local and Systemic Inflammatory Processes Induced by Bothrops moojeni Venom and the Lys-49 Phospholipase A2 in a Rat Model. AB - Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein that modulates anti-inflammatory process and its therapeutic potential has recently been recognized in a range of systemic inflammatory disorders. The effect of the N-terminal peptide Ac2-26 of AnxA1 on the toxic activities of Bothrops moojeni crude venom (CV) and its myotoxin II (MjTX-II) were evaluated using a peritonitis rat model. Peritonitis was induced by the intraperitoneal injection of either CV or MjTX-II, a Lys-49 phospholipase A2. Fifteen minutes after the injection, the rats were treated with either Ac2-26 or PBS. Four hours later, the CV and MjTX-II induced peritonitis were characterized by neutrophilia (in the peritoneal exudate, blood and mesentery) and increased number of mesenteric degranulated mast cells and macrophages. At 24 hours post-injection, the local inflammatory response was attenuated in the CV-induced peritonitis while the MjTX-II group exhibited neutrophilia (peritoneal exudates and blood). Ac2-26 treatment prevented the influx of neutrophils in MjTX-II-induced peritonitis and diminished the proportion of mesenteric degranulated mast cells and macrophages in CV induced peritonitis. Additionally, CV and MjTX-II promoted increased levels of IL 1beta and IL-6 in the peritoneal exudates which were significantly reduced after Ac2-26 treatment. At 4 and 24 hours, the endogenous expression of AnxA1 was upregulated in the mesenteric neutrophils (CV and MjTX-II groups) and mast cells (CV group). In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules. Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules. Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment. PMID- 26147725 TI - Exposure to 100% Oxygen Abolishes the Impairment of Fracture Healing after Thoracic Trauma. AB - In polytrauma patients a thoracic trauma is one of the most critical injuries and an important trigger of post-traumatic inflammation. About 50% of patients with thoracic trauma are additionally affected by bone fractures. The risk for fracture malunion is considerably increased in such patients, the pathomechanisms being poorly understood. Thoracic trauma causes regional alveolar hypoxia and, subsequently, hypoxemia, which in turn triggers local and systemic inflammation. Therefore, we aimed to unravel the role of oxygen in impaired bone regeneration after thoracic trauma. We hypothesized that short-term breathing of 100% oxygen in the early post-traumatic phase ameliorates inflammation and improves bone regeneration. Mice underwent a femur osteotomy alone or combined with blunt chest trauma 100% oxygen was administered immediately after trauma for two separate 3 hour intervals. Arterial blood gas tensions, microcirculatory perfusion and oxygenation were assessed at 3, 9 and 24 hours after injury. Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma. Bone healing was assessed on day 7, 14 and 21. Thoracic trauma induced pulmonary and systemic inflammation and impaired bone healing. Short-term exposure to 100% oxygen in the acute post-traumatic phase significantly attenuated systemic and local inflammatory responses and improved fracture healing without provoking toxic side effects, suggesting that hyperoxia could induce anti-inflammatory and pro-regenerative effects after severe injury. These results suggest that breathing of 100% oxygen in the acute post-traumatic phase might reduce the risk of poorly healing fractures in severely injured patients. PMID- 26147726 TI - New Hybrid Algorithms for Estimating Tree Stem Diameters at Breast Height Using a Two Dimensional Terrestrial Laser Scanner. AB - In this paper, a new algorithm to improve the accuracy of estimating diameter at breast height (DBH) for tree trunks in forest areas is proposed. First, the information is collected by a two-dimensional terrestrial laser scanner (2DTLS), which emits laser pulses to generate a point cloud. After extraction and filtration, the laser point clusters of the trunks are obtained, which are optimized by an arithmetic means method. Then, an algebraic circle fitting algorithm in polar form is non-linearly optimized by the Levenberg-Marquardt method to form a new hybrid algorithm, which is used to acquire the diameters and positions of the trees. Compared with previous works, this proposed method improves the accuracy of diameter estimation of trees significantly and effectively reduces the calculation time. Moreover, the experimental results indicate that this method is stable and suitable for the most challenging conditions, which has practical significance in improving the operating efficiency of forest harvester and reducing the risk of causing accidents. PMID- 26147728 TI - UAV Deployment Exercise for Mapping Purposes: Evaluation of Emergency Response Applications. AB - Exploiting the decrease of costs related to UAV technology, the humanitarian community started piloting the use of similar systems in humanitarian crises several years ago in different application fields, i.e., disaster mapping and information gathering, community capacity building, logistics and even transportation of goods. Part of the author's group, composed of researchers in the field of applied geomatics, has been piloting the use of UAVs since 2006, with a specific focus on disaster management application. In the framework of such activities, a UAV deployment exercise was jointly organized with the Regional Civil Protection authority, mainly aimed at assessing the operational procedures to deploy UAVs for mapping purposes and the usability of the acquired data in an emergency response context. In the paper the technical features of the UAV platforms will be described, comparing the main advantages/disadvantages of fixed-wing versus rotor platforms. The main phases of the adopted operational procedure will be discussed and assessed especially in terms of time required to carry out each step, highlighting potential bottlenecks and in view of the national regulation framework, which is rapidly evolving. Different methodologies for the processing of the acquired data will be described and discussed, evaluating the fitness for emergency response applications. PMID- 26147729 TI - Sorting Olive Batches for the Milling Process Using Image Processing. AB - The quality of virgin olive oil obtained in the milling process is directly bound to the characteristics of the olives. Hence, the correct classification of the different incoming olive batches is crucial to reach the maximum quality of the oil. The aim of this work is to provide an automatic inspection system, based on computer vision, and to classify automatically different batches of olives entering the milling process. The classification is based on the differentiation between ground and tree olives. For this purpose, three different species have been studied (Picudo, Picual and Hojiblanco). The samples have been obtained by picking the olives directly from the tree or from the ground. The feature vector of the samples has been obtained on the basis of the olive image histograms. Moreover, different image preprocessing has been employed, and two classification techniques have been used: these are discriminant analysis and neural networks. The proposed methodology has been validated successfully, obtaining good classification results. PMID- 26147727 TI - Localized Surface Plasmon Resonance Biosensing: Current Challenges and Approaches. AB - Localized surface plasmon resonance (LSPR) has emerged as a leader among label free biosensing techniques in that it offers sensitive, robust, and facile detection. Traditional LSPR-based biosensing utilizes the sensitivity of the plasmon frequency to changes in local index of refraction at the nanoparticle surface. Although surface plasmon resonance technologies are now widely used to measure biomolecular interactions, several challenges remain. In this article, we have categorized these challenges into four categories: improving sensitivity and limit of detection, selectivity in complex biological solutions, sensitive detection of membrane-associated species, and the adaptation of sensing elements for point-of-care diagnostic devices. The first section of this article will involve a conceptual discussion of surface plasmon resonance and the factors affecting changes in optical signal detected. The following sections will discuss applications of LSPR biosensing with an emphasis on recent advances and approaches to overcome the four limitations mentioned above. First, improvements in limit of detection through various amplification strategies will be highlighted. The second section will involve advances to improve selectivity in complex media through self-assembled monolayers, "plasmon ruler" devices involving plasmonic coupling, and shape complementarity on the nanoparticle surface. The following section will describe various LSPR platforms designed for the sensitive detection of membrane-associated species. Finally, recent advances towards multiplexed and microfluidic LSPR-based devices for inexpensive, rapid, point-of-care diagnostics will be discussed. PMID- 26147730 TI - Using Hand Grip Force as a Correlate of Longitudinal Acceleration Comfort for Rapid Transit Trains. AB - Longitudinal acceleration comfort is one of the essential metrics used to evaluate the ride comfort of train. The aim of this study was to investigate the effectiveness of using hand grip force as a correlate of longitudinal acceleration comfort of rapid transit trains. In the paper, a motion simulation system was set up and a two-stage experiment was designed to investigate the role of the grip force on the longitudinal comfort of rapid transit trains. The results of the experiment show that the incremental grip force was linearly correlated with the longitudinal acceleration value, while the incremental grip force had no correlation with the direction of the longitudinal acceleration vector. The results also show that the effects of incremental grip force and acceleration duration on the longitudinal comfort of rapid transit trains were significant. Based on multiple regression analysis, a step function model was established to predict the longitudinal comfort of rapid transit trains using the incremental grip force and the acceleration duration. The feasibility and practicably of the model was verified by a field test. Furthermore, a comparative analysis shows that the motion simulation system and the grip force based model were valid to support the laboratory studies on the longitudinal comfort of rapid transit trains. PMID- 26147731 TI - GUDM: Automatic Generation of Unified Datasets for Learning and Reasoning in Healthcare. AB - A wide array of biomedical data are generated and made available to healthcare experts. However, due to the diverse nature of data, it is difficult to predict outcomes from it. It is therefore necessary to combine these diverse data sources into a single unified dataset. This paper proposes a global unified data model (GUDM) to provide a global unified data structure for all data sources and generate a unified dataset by a "data modeler" tool. The proposed tool implements user-centric priority based approach which can easily resolve the problems of unified data modeling and overlapping attributes across multiple datasets. The tool is illustrated using sample diabetes mellitus data. The diverse data sources to generate the unified dataset for diabetes mellitus include clinical trial information, a social media interaction dataset and physical activity data collected using different sensors. To realize the significance of the unified dataset, we adopted a well-known rough set theory based rules creation process to create rules from the unified dataset. The evaluation of the tool on six different sets of locally created diverse datasets shows that the tool, on average, reduces 94.1% time efforts of the experts and knowledge engineer while creating unified datasets. PMID- 26147732 TI - Inverted Perceptual Judgment of Nociceptive Stimuli at Threshold Level following Inconsistent Cues. AB - OBJECTIVE: The perception of pain is susceptible to modulation by psychological and contextual factors. It has been shown that subjects judge noxious stimuli as more painful in a respective suggestive context, which disappears when the modifying context is resolved. However, a context in which subjects judge the painfulness of a nociceptive stimulus in exactly the opposite direction to that of the cues has never been shown so far. METHODS: Nociceptive stimuli (300 ms intranasal gaseous CO2) at the individual pain threshold level were applied after a visual cue announcing the stimulus as either "no pain", merely a "stimulus", or "pain". Among the stimuli at threshold level, other CO2 stimuli that were clearly below or above pain threshold were randomly interspersed. These were announced beforehand in 12 subjects randomly with correct or incorrect cues, i.e., clearly painful or clearly non-painful stimuli were announced equally often as not painful or painful. By contrast, in a subsequent group of another 12 subjects, the stimuli were always announced correctly with respect to the evoked pain. RESULTS: The random and often incorrect announcement of stimuli clearly below or above pain threshold caused the subjects to rate the stimuli at pain-threshold level in the opposite direction of the cue, i.e., when the stimuli were announced as "pain" significantly more often than as non-painful and vice versa (p < 10( 4)). By contrast, in the absence of incongruence between announcement and perception of the far-from-threshold stimuli, stimuli at pain threshold were rated in the cued direction. CONCLUSIONS: The present study revealed the induction of associations incongruent with a given message in the perception of pain. We created a context of unreliable cues whereby subjects perceived the stimulus opposite to that suggested by a prior cue, i.e., potentially nociceptive stimuli at pain threshold level that were announced as painful were judged as non painful and vice versa. These findings are consistent with reported data on the effects of distrust on non-painful cognitive responses. PMID- 26147733 TI - An A2B Adenosine Receptor Agonist Promotes Th17 Autoimmune Responses in Experimental Autoimmune Uveitis (EAU) via Dendritic Cell Activation. AB - We have recently reported that, although adenosine receptor (AR) agonists have a suppressive effect on Th1 autoreactive T cells, their effect on Th17 autoreactive T cells and gammadelta T cells is stimulatory and this effect is mainly mediated via A2A adenosine receptors (A2ARs). In this study, we further demonstrate that treatment of C57BL/6 (B6) mice with a selective A2B adenosine receptor (A2BR) agonist greatly enhanced the development of experimental autoimmune uveitis (EAU), whereas treatment with an A2BR antagonist significantly ameliorated severity of EAU. The A2BR agonist-treated mice showed augmented Th17, but not Th1, responses. Mechanistic studies showed that the A2BR agonist-induced enhancement of the Th17 response was significantly lower when TCR-delta-/- mice received the same treatment and that transfer of gammadelta T cells into TCR delta-/- mice partially restored this effect. We also showed that dendritic cells (DCs) from A2BR agonist-treated mice showed a significantly increased ability to activate gammadelta T cells and Th17 autoreactive T cells. Thus, our previous studies have shown that, in EAU, activated gammadelta T cells possess greatly increased ability to enhance Th17 autoimmune responses. In the present study, we showed that exposure of DCs to A2BR agonist facilitated gammadelta T cell activation, leading to augmented Th17 responses and progressive EAU development. Our results further support our previous finding that AR agonists have distinct effects on Th1 and Th17 autoimmune responses. PMID- 26147734 TI - Mating Reverses Actuarial Aging in Female Queensland Fruit Flies. AB - Animals that have a long pre-reproductive adult stage often employ mechanisms that minimize aging over this period in order to preserve reproductive lifespan. In a remarkable exception, one tephritid fruit fly exhibits substantial pre reproductive aging but then mitigates this aging during a diet-dependent transition to the reproductive stage, after which life expectancy matches that of newly emerged flies. Here, we ascertain the role of nutrients, sexual maturation and mating in mitigation of previous aging in female Queensland fruit flies. Flies were provided one of three diets: 'sugar', 'essential', or 'yeast-sugar'. Essential diet contained sugar and micronutrients found in yeast but lacked maturation-enabling protein. At days 20 and 30, a subset of flies on the sugar diet were switched to essential or yeast-sugar diet, and some yeast-sugar fed flies were mated 10 days later. Complete mitigation of actuarial aging was only observed in flies that were switched to a yeast-sugar diet and mated, indicating that mating is key. Identifying the physiological processes associated with mating promise novel insights into repair mechanisms for aging. PMID- 26147736 TI - Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes. AB - BACKGROUND: Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood. METHODS: Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors. RESULTS: The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors. CONCLUSIONS: Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors. PMID- 26147738 TI - Data Normalization of (1)H NMR Metabolite Fingerprinting Data Sets in the Presence of Unbalanced Metabolite Regulation. AB - Data normalization is an essential step in NMR-based metabolomics. Conducted properly, it improves data quality and removes unwanted biases. The choice of the appropriate normalization method is critical and depends on the inherent properties of the data set in question. In particular, the presence of unbalanced metabolic regulation, where the different specimens and cohorts under investigation do not contain approximately equal shares of up- and down-regulated features, may strongly influence data normalization. Here, we demonstrate the suitability of the Shapiro-Wilk test to detect such unbalanced regulation. Next, employing a Latin-square design consisting of eight metabolites spiked into a urine specimen at eight different known concentrations, we show that commonly used normalization and scaling methods fail to retrieve true metabolite concentrations in the presence of increasing amounts of glucose added to simulate unbalanced regulation. However, by learning the normalization parameters on a subset of nonregulated features only, Linear Baseline Normalization, Probabilistic Quotient Normalization, and Variance Stabilization Normalization were found to account well for different dilutions of the samples without distorting the true spike-in levels even in the presence of marked unbalanced metabolic regulation. Finally, the methods described were applied successfully to a real world example of unbalanced regulation, namely, a set of plasma specimens collected from patients with and without acute kidney injury after cardiac surgery with cardiopulmonary bypass use. PMID- 26147739 TI - Muscles and their role in episodic tension-type headache: implications for treatment. AB - BACKGROUND AND OBJECTIVE: Tension-type headache (TTH) imposes a heavy burden on the global population but remains incompletely understood and poorly managed. DATABASES AND DATA TREATMENT: Here, we review current knowledge of peripheral factors involved in the mechanism of TTH and make recommendations for the treatment of episodic TTH based on these. RESULTS: Peripheral activation or sensitization of myofascial nociceptors is most probably involved in the development of muscle pain and the acute episode of TTH. Repetitive episodes of muscle pain may sensitize the central nervous system resulting in progression of TTH to the chronic form. Thus, muscular factors may be responsible not only for the acute headache episode but also for chronification of the disorder. Simple analgesics and non-steroidal anti-inflammatory drugs are the mainstays of management of individual headache episodes. Ibuprofen 400 mg and aspirin 1000 mg are recommended as drugs of first choice based on treatment effect, safety profile and costs. Non-pharmacological therapies include electromyographic biofeedback, physiotherapy and muscle relaxation therapy. Future studies should aim to identify the triggers of peripheral nociception and how to avoid peripheral and central sensitization. There is a need for more effective, faster acting drugs for acute TTH. CONCLUSION: Muscular factors play an important role in episodic TTH. Ibuprofen 400 mg and aspirin 1000 mg are recommended as drugs of first choice. PMID- 26147740 TI - Yeast with bacteriocin from ruminal bacteria enhances glucose utilization, reduces ectopic fat accumulation, and alters cecal microbiota in dietary-induced obese mice. AB - BACKGROUND: This study investigated the effect of yeast with bacteriocin (YB) on the homeostasis of lipid and glucose in diet-induced obese (DIO) mice. Seven-week old C57BL/6 male mice were fed with a Western diet for 24 weeks to induce obesity. These DIO mice were randomly assigned to 2 groups: obese control (WS) and WYB [0.125 MUg YB per g body weight (BW)]. YB was administered daily to the WYB mice in the last 4 weeks, while an equal volume of normal saline was administered to the WS mice. RESULTS: YB caused a significant reduction in BW, and in plasma levels of total cholesterol and glucose. Less hepatic lipid accumulation and smaller adipocytes were observed in WYB mice. WYB mice had higher lipid catabolism in liver and adipose tissue. Compared with WS mice, WYB mice had higher glycolysis in the liver and muscles. YB suppressed hepatic GLUT5 expression, altered the composition of cecal microbiota, and also caused more efficient carbohydrate utilization for energy expenditure. CONCLUSION: YB resulted in body weight loss, promoted lipid catabolism and carbohydrate utilization; it also modulated cecal microbiota, and therefore partially improved the health of obese mice. PMID- 26147741 TI - High preoperative bilirubin values protect against reperfusion injury after live donor liver transplantation. AB - Heme Oxygenase-1 and its product biliverdin/bilirubin have been demonstrated to protect against ischemia/reperfusion injury (IRI). We investigated whether increased preoperative bilirubin values of transplant recipients decrease IRI. Preoperative bilirubin levels of live donor liver recipients were correlated to postoperative liver transaminase as a marker of IRI. Additionally, two recipient groups with pretransplant bilirubin levels >24 MUmol/l (n = 348) and <=24 MUmol/l (n = 118) were compared. Post-transplant liver function, complications, length of hospital stay, and patient and graft survival were assessed. Preoperative bilirubin levels were negatively correlated to the postoperative increase in transaminases suggesting a protective effect against IRI. The maximal rise of ALT after transplantation in high versus low bilirubin patients was 288 (-210-2457) U/l vs. 375 (-11-2102) U/l, P = 0.006. Bilirubin remained a significant determining factor in a multivariate linear regression analysis. The MELD score and its individual components as a marker of severity of chronic liver disease were significantly higher in the high versus low bilirubin group (P < 0.001). Despite this, overall complication rate (21.0% vs. 21.2%, P = 0.88), hospital stay [13 (4-260) vs. 14 (6-313) days, P = 0.93), and 1-year graft survival (90.8% vs. 89.0%, P = 0.62) were similar in both groups. High bilirubin levels of liver recipients before live donor transplantation is associated with decreased postoperative IRI. PMID- 26147743 TI - The contribution of endophytic bacteria to Albizia lebbeck-mediated phytoremediation of tannery effluent contaminated soil. AB - Toxicity of chromium often impairs the remediation capacity of plants used in phytoremediation of polluted soils. In this study, we have identified Albizia lebbeck as a prospective chromium hyperaccumulator and examined cultivable diversity of endophytes present in chromium-treated and control saplings. High numbers (22-100%) of endophytic bacteria, isolated from root, stem, and leaf tissues, could tolerate elevated (1-3 mM) concentrations of K2CrO7. 16S rRNA gene sequence-based phylogenetic analysis showed that the 118 isolates obtained comprised of 17 operational taxonomic units affiliated with the proteobacterial genera Rhizobium (18%), Marinomonas (1%), Pseudomonas (16%), and Xanthomonas (7%) but also with members of Firmicutes genera, such as Bacillus (35%) and Salinococcus (3%). The novel isolates belonging to Salinococcus and Bacillus could tolerate high K2CrO7 concentrations (3 mM) and also showed elevated activity of chromate reductase. In addition, majority (%) of the endophytic isolates also showed production of indole-3-acetic acid. Taken together, our results indicate that the innate endophytic bacterial community assists plants in reducing heavy metal toxicity. PMID- 26147742 TI - Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. AB - HIV drug resistance assessments and interpretations can be obtained from genotyping (GT), virtual phenotyping (VP) and laboratory-based phenotyping (PT). We compared resistance calls obtained from GT and VP with those from PT (GT-PT and VP-PT) among CRF01_AE and subtype B HIV-1 infected patients. GT predictions were obtained from the Stanford HIV database. VP and PT were obtained from Janssen Diagnostics BVBA's vircoType(TM) HIV-1 and Antivirogram(r), respectively. With PT assumed as the "gold standard," the area under the curve (AUC) and the Bland-Altman plot were used to assess the level of agreement in resistance interpretations. A total of 80 CRF01_AE samples from Asia and 100 subtype B from Janssen Diagnostics BVBA's database were analysed. CRF01_AE showed discordances ranging from 3 to 27 samples for GT-PT and 1 to 20 samples for VP-PT. The GT-PT and VP-PT AUCs were 0.76-0.97 and 0.81-0.99, respectively. Subtype B showed 3-61 discordances for GT-PT and 2-75 discordances for VP-PT. The AUCs ranged from 0.55 to 0.95 for GT-PT and 0.55 to 0.97 for VP-PT. Didanosine had the highest proportion of discordances and/or AUC in all comparisons. The patient with the largest didanosine FC difference in each subtype harboured Q151M mutation. Overall, GT and VP predictions for CRF01_AE performed significantly better than subtype B for three NRTIs. Although discrepancies exist, GT and VP resistance interpretations in HIV-1 CRF01_AE strains were highly robust in comparison with the gold-standard PT. PMID- 26147744 TI - Presentation of Diagnostic Information to Doctors May Change Their Interpretation and Clinical Management: A Web-Based Randomised Controlled Trial. AB - BACKGROUND: There is little evidence on how best to present diagnostic information to doctors and whether this makes any difference to clinical management. We undertook a randomised controlled trial to see if different data presentations altered clinicians' decision to further investigate or treat a patient with a fictitious disorder ("Green syndrome") and their ability to determine post-test probability. METHODS: We recruited doctors registered with the United Kingdom's largest online network for medical doctors between 10 July and 6" November 2012. Participants were randomised to one of four arms: (a) text summary of sensitivity and specificity, (b) Fagan's nomogram, (c) probability modifying plot (PMP), (d) natural frequency tree (NFT). The main outcome measure was the decision whether to treat, not treat or undertake a brain biopsy on the hypothetical patient and the correct post-test probability. Secondary outcome measures included knowledge of diagnostic tests. RESULTS: 917 participants attempted the survey and complete data were available from 874 (95.3%). Doctors randomized to the PMP and NFT arms were more likely to treat the patient than those randomized to the text-only arm. (ORs 1.49, 95% CI 1.02, 2.16) and 1.43, 95% CI 0.98, 2.08 respectively). More patients randomized to the PMP (87/218 39.9%) and NFT (73/207-35.3%) arms than the nomogram (50/194-25.8%) or text only (30/255-11.8%) arms reported the correct post-test probability (p <0.001). Younger age, postgraduate training and higher self-rated confidence all predicted better knowledge performance. Doctors with better knowledge were more likely to view an optional learning tutorial (OR per correct answer 1.18, 95% CI 1.06, 1.31). CONCLUSIONS: Presenting diagnostic data using a probability-modifying plot or natural frequency tree influences the threshold for treatment and improves interpretation of tests results compared to text summary of sensitivity and specificity or Fagan's nomogram. PMID- 26147745 TI - Prognostic impact of CD56 in pediatric AML. PMID- 26147746 TI - Freestanding membranes of cross-linked gold nanoparticles: novel functional materials for electrostatic actuators. AB - Their tunable electrical, optical, and mechanical properties make freestanding membranes of organically cross-linked gold nanoparticles (GNPs) interesting materials for applications in micro- and nanoelectromechanical systems. Here, we demonstrate the application of alpha,omega-alkanedithiol-cross-linked GNP membranes as electrostatically driven actuators. The devices were fabricated by depositing these membranes (thickness 29-45 nm) onto cylindrical cavities (diameter ~200 MUm; depth ~8-15 MUm), which were lithographically patterned in a SU-8 resist. Applying voltages of up to +/-40 V across the membrane and the silicon substrate deflected the membranes by several hundreds of nanometers, as measured by atomic force microscopy, confocal microscopy, and interferometry. A simple electrostatic model, which takes into account the membranes' mechanical properties, was used to interpret the experimental data. PMID- 26147747 TI - UHRF1 promotes proliferation of gastric cancer via mediating tumor suppressor gene hypermethylation. AB - Epigenetic changes play significant roles in cancer development. UHRF1, an epigenetic regulator, has been shown to be overexpressed and to coordinate tumor suppressor gene (TSG) silencing in several cancers. In a previous study, we found that UHRF1 promoted gastric cancer (GC) invasion and metastasis. However, the role and underlying mechanism of UHRF1 in GC carcinogenesis remain largely unknown. In the present study, we investigated UHRF1 expression and function in GC proliferation and explored its downstream regulatory mechanism. The results demonstrated that UHRF1 overexpression was an independent and significant predictor of GC prognosis. Downregulation of UHRF1 suppressed GC proliferation and growth in vitro and in vivo, and UHRF1 upregulation showed opposite effects. Furthermore, downregulation of UHRF1 reactivated 7 TSGs, including CDX2, CDKN2A, RUNX3, FOXO4, PPARG, BRCA1 and PML, via promoter demethylation. These results provide insight into the GC proliferation process, and suggest that targeting UHRF1 represents a new therapeutic approach to block GC development. PMID- 26147748 TI - Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain. AB - As part of the cellular adaptation to limiting oxygen availability in animals, the expression of a large set of genes is activated by the upregulation of the hypoxia-inducible transcription factors (HIFs). Therapeutic activation of the natural human hypoxic response can be achieved by the inhibition of the hypoxia sensors for the HIF system, i.e. the HIF prolyl-hydroxylases (PHDs). Here, we report studies on tricyclic triazole-containing compounds as potent and selective PHD inhibitors which compete with the 2-oxoglutarate co-substrate. One compound (IOX4) induces HIFalpha in cells and in wildtype mice with marked induction in the brain tissue, revealing that it is useful for studies aimed at validating the upregulation of HIF for treatment of cerebral diseases including stroke. PMID- 26147749 TI - Feasibility of Computed Tomography-Guided Methods for Spatial Normalization of Dopamine Transporter Positron Emission Tomography Image. AB - BACKGROUND: Spatial normalization is a prerequisite step for analyzing positron emission tomography (PET) images both by using volume-of-interest (VOI) template and voxel-based analysis. Magnetic resonance (MR) or ligand-specific PET templates are currently used for spatial normalization of PET images. We used computed tomography (CT) images acquired with PET/CT scanner for the spatial normalization for [18F]-N-3-fluoropropyl-2-betacarboxymethoxy-3-beta-(4 iodophenyl) nortropane (FP-CIT) PET images and compared target-to-cerebellar standardized uptake value ratio (SUVR) values with those obtained from MR- or PET guided spatial normalization method in healthy controls and patients with Parkinson's disease (PD). METHODS: We included 71 healthy controls and 56 patients with PD who underwent [18F]-FP-CIT PET scans with a PET/CT scanner and T1-weighted MR scans. Spatial normalization of MR images was done with a conventional spatial normalization tool (cvMR) and with DARTEL toolbox (dtMR) in statistical parametric mapping software. The CT images were modified in two ways, skull-stripping (ssCT) and intensity transformation (itCT). We normalized PET images with cvMR-, dtMR-, ssCT-, itCT-, and PET-guided methods by using specific templates for each modality and measured striatal SUVR with a VOI template. The SUVR values measured with FreeSurfer-generated VOIs (FSVOI) overlaid on original PET images were also used as a gold standard for comparison. RESULTS: The SUVR values derived from all four structure-guided spatial normalization methods were highly correlated with those measured with FSVOI (P < 0.0001). Putaminal SUVR values were highly effective for discriminating PD patients from controls. However, the PET-guided method excessively overestimated striatal SUVR values in the PD patients by more than 30% in caudate and putamen, and thereby spoiled the linearity between the striatal SUVR values in all subjects and showed lower disease discrimination ability. Two CT-guided methods showed comparable capability with the MR-guided methods in separating PD patients from controls and showed better correlation between putaminal SUVR values and the parkinsonian motor severity than the PET-guided method. CONCLUSION: CT-guided spatial normalization methods provided reliable striatal SUVR values comparable to those obtained with MR-guided methods. CT-guided methods can be useful for analyzing dopamine transporter PET images when MR images are unavailable. PMID- 26147750 TI - Evaluation of serum zinc level in patients with newly diagnosed and resistant alopecia areata. AB - BACKGROUND: Alopecia areata (AA) is a non-scarring, autoimmune, inflammatory hair loss disease. Zinc is a trace element involved in important functional activities of hair follicles. PURPOSE: To evaluate serum zinc levels in patients with newly diagnosed and resistant lesions of AA in comparison to age- and sex-matched healthy controls. METHODS: The present study included 100 subjects: 50 patients with AA divided into two equally distributed subgroups (25 patients with recent onset AA [subgroup 1] and 25 patients with resistant AA [subgroup 2]) and 50 age- and sex-matched healthy controls. Serum zinc levels were assessed in all subjects. Comparison of mean serum zinc levels was done between all patients and controls, between patients' subgroups as well as between patient's subgroup and controls. Correlations between serum zinc level and extent of AA and its duration were also done in all patients and each patient's subgroup. RESULTS: A significantly lower serum zinc level was found in patients with AA compared with controls and was significantly lower in patients with resistant AA compared to patients with newly diagnosed AA. Significant inverse correlations existed between serum zinc level, severity of AA, and disease duration in all patients as well as in patients with resistant AA. CONCLUSION: Lower serum zinc level existed in patients with AA and correlated inversely with disease duration, severity of AA, and its resistance to therapies. Therefore, assessment of serum zinc level in patients with AA appears useful as a marker of severity, disease duration, and resistance to therapies. Accordingly, zinc supplements may provide a therapeutic benefit. PMID- 26147751 TI - New Insight Into Metformin Action: Regulation of ChREBP and FOXO1 Activities in Endothelial Cells. AB - Metformin has been considered a potential adjunctive therapy in treating poorly controlled type 1 diabetes with obesity and insulin resistance, owing to its potent effects on improving insulin sensitivity. However, the underlying mechanism of metformin's vascular protective effects remains obscure. Thioredoxin interacting protein (TXNIP), a key regulator of cellular redox state induced by high-glucose concentration, decreases thioredoxin reductase activity and mediates apoptosis induced by oxidative stress. Here we report that high glucose-induced endothelial dysfunction is associated with induction of TXNIP expression in primary human aortic endothelial cells exposed to high-glucose conditions, whereas the metformin treatment suppresses high-glucose-induced TXNIP expression at mRNA and protein levels. We further show that metformin decreases the high glucose-stimulated nuclear entry rate of two transcription factors, carbohydrate response element-binding protein (ChREBP) and forkhead box O1 (FOXO1), as well as their recruitment on the TXNIP promoter. An AMP-activated protein kinase inhibitor partially compromised these metformin effects. Our data suggest that endothelial dysfunction resulting from high-glucose concentrations is associated with TXNIP expression. Metformin down-regulates high-glucose-induced TXNIP transcription by inactivating ChREBP and FOXO1 in endothelial cells, partially through AMP-activated protein kinase activation. PMID- 26147752 TI - Identifying Coronary Artery Disease in Asymptomatic Middle-Aged Sportsmen: The Additional Value of Pulse Wave Velocity. AB - BACKGROUND: Cardiovascular screening may benefit middle-aged sportsmen, as coronary artery disease (CAD) is the main cause of exercise-related sudden cardiac death. Arterial stiffness, as measured by pulse wave velocity (PWV), may help identify sportsmen with subclinical CAD. We examined the additional value of PWV measurements to traditional CAD risk factors for identifying CAD. METHODS: From the Measuring Athlete's Risk of Cardiovascular events (MARC) cohort of asymptomatic, middle-aged sportsmen who underwent low-dose Cardiac CT (CCT) after routine sports medical examination (SME), 193 consecutive sportsmen (aged 55 +/- 6.6 years) were included with additional PWV measurements before CCT. Sensitivity, specificity and predictive values of PWV values (>8.3 and >7.5 m/s) assessed by Arteriograph were used to identify CAD (coronary artery calcium scoring >= 100 Agatston Units or coronary CT angiography luminal stenosis >= 50%) and to assess the additional diagnostic value of PWV to established cardiovascular risk factors. RESULTS: Forty-seven sportsmen (24%) had CAD on CCT. They were older (58.9 vs. 53.8 years, p<0.001), had more hypertension (17 vs. 4%, p=0.003), higher cholesterol levels (5.7 vs. 5.4 mmol/l) p=0.048), and more often were (ever) smokers (55 vs. 34%, p=0.008). Mean PWV was higher in those with CAD (8.9 vs. 8.0 m/s, p=0.017). For PWV >8.3m/s respectively >7.5 m/s sensitivity to detect CAD on CT was 43% and 74%, specificity 69% and 45%, positive predictive value 31% and 30%, and negative predictive value 79% and 84%. Adding PWV to traditional risk factor models did not change the area under the curve (from 0.78 (95% CI = 0.709-0.848)) to AUC 0.78 (95% CI 0.710-0.848, p = 0.99)) for prediction of CAD on CCT. CONCLUSIONS: Limited additional value was found for PWV on top of established risk factors to identify CAD. PWV might still have a role to identify CAD in middle-aged sportsmen if risk factors such as cholesterol are unknown. PMID- 26147753 TI - Will Trespassers Be Prosecuted or Assessed According to Their Merits? A Consilient Interpretation of Territoriality in a Group-Living Carnivore, the European Badger (Meles meles). AB - Socio-spatial interactions of Carnivores have traditionally been described using the vocabulary of territoriality and aggression, with scent marks interpreted as 'scent fences'. Here, we investigate the role of olfactory signals in assumed territorial marking of group-living solitary foragers using European badgers Meles meles as a model. We presented anal gland secretions (n = 351) from known individuals to identifiable recipients (n = 187), to assess response-variation according to familiarity (own-group, neighbours, strangers) and spatial context (in-context: at a shared border; out-of-context: at an unshared border/ the main sett). Sniffing and over-marking (with subcaudal gland secretion) responses were strongest to anal gland secretions from strangers, intermediate to neighbouring group and weakest to own-group members. Secretions from both, strangers and neighbours, were sniffed for longer than were own-group samples, although neighbour-secretion presented out-of-context evoked no greater interest than in context. On an individual level, responses were further moderated by the relevance of individual-specific donor information encoded in the secretion, as it related to the physiological state of the responder. There was a trend bordering on significance for males to sniff for longer than did females, but without sex-related differences in the frequency of subcaudal over-marking responses, and males over-marked oestrous female secretions more than non oestrous females. There were no age-class related differences in sniff-duration or in over-marking. Evaluating these results in the context of the Familiarity hypothesis, the Threat-level hypothesis, and the Individual advertisement hypothesis evidences that interpretations of territorial scent-marks depicting rigid and potentially agonistic discrimination between own- and foreign-group conspecifics are overly simplistic. We use our findings to advance conceptual understanding of badger socio-spatial ecology, and the general context of territoriality and group-range dynamics. PMID- 26147754 TI - Growth hormone replacement does not increase mortality in patients with childhood onset growth hormone deficiency. AB - CONTEXT: Long-term safety of growth hormone (GH) treatment is an area of much debate. Studies including children treated with GH not only due to GHD, but also due to non-GHD causes like idiopathic short stature or like short stature in children born small for gestational age have suggested that GH treatment is associated with increased mortality or stroke. OBJECTIVE: To study the impact of GH replacement on overall and cause-specific mortality in childhood-onset GHD (CO GHD) patients. DESIGN: A nationwide population-based registry study on patients with CO GHD and general population controls matched on age and gender. Mortality hazard ratios (HRs) were computed comparing patients and controls, and comparing GH-replaced patients and non-GH-replaced patients, using Cox regression. Comparing GH- and non-GH-replaced patients HRs were adjusted for birth year, year of diagnosis, gender, irradiation, ACTH insufficiency and primary disease. PATIENTS AND CONTROLS: A total of 494 patients with CO GHD each matched with 100 general population controls were included. RESULTS: Mortality was substantially increased comparing patients with CO GHD and general population controls, HR = 7.51 (95% CI = 6.06-9.31). Comparing GH-replaced patients with non-GH-replaced patients mortality was significantly decreased in total (HR = 0.27, CI = 0.17 0.43) and due to malignancy (HR = 0.14, CI = 0.07-0.28) in GH-replaced patients. Adjusting for relevant confounders, this decrease remained significant both in total (HR = 0.56, CI = 0.32-0.96) and due to malignancy (HR = 0.33, CI = 0.16 0.69). Overall and cause-specific mortality was increased in both GH-replaced and non-GH-replaced patients compared to general population controls, but mortality was generally highest in non-GH-replaced patients. CONCLUSION: The present data from a national cohort of patients with CO GHD do not support the suggestion that GH replacement is associated with increased mortality. PMID- 26147755 TI - Pediatric vasculitis: advances in treatment. AB - PURPOSE OF REVIEW: This study will provide an overview of the recent advances in treatment of chronic systemic vasculitis in childhood. RECENT FINDINGS: Advances in the treatment of chronic primary systemic vasculitis have significantly improved outcomes for patients in the last several decades. Conventional life saving treatments like cyclophosphamide and corticosteroids have predominated as mainstay therapy for severe or extensive disease; however, evidence supporting the effectiveness of newer treatments such as rituximab and other biologic agents is increasing. Improved collaboration through international registries and multicentered initiatives has enabled increased research and generation of pediatric specific data. Such efforts are essential to the development of evidence-based treatment guidelines and validated assessment tools in the future. SUMMARY: Although most of our understanding about treatment of childhood vasculitis has been derived from adult data, pediatric data continue to accumulate. Evidence for newer treatments and alternative treatment strategies is continually evolving. PMID- 26147756 TI - Advances in the treatment of polyarticular juvenile idiopathic arthritis. AB - PURPOSE OF REVIEW: To review recent advances in the management strategies of polyarticular course juvenile idiopathic arthritis (JIA) and identify unanswered questions and avenues for further research. RECENT FINDINGS: There is evidence for an early, aggressive, treat-to-target approach for polyarticular JIA. Clinical disease activity criteria have been recently defined and validated, including criteria for inactive disease and the juvenile arthritis disease activity score (JADAS). There is a need for evidence-based, defined disease targets and biomarkers for prediction of response, including targets for remission induction, and guidelines on drug withdrawal. Recent treatment consensus plans and guidelines are discussed and compared, including the 2015 NHS England clinical policy statement, the 2014 Childhood Arthritis and Rheumatology Research Alliance (CARRA) treatment plans and the 2011 American College of Rheumatology (ACR) guidelines. Evidence for new agents such as tocilizumab, rituximab, golimumab, ustekinumab, certolizumab and tofacitinib is promising: the recent clinical trials are summarized here. Stratification of individual patient treatment remains a goal, and predictive biomarkers have been shown to predict success in the withdrawal of methotrexate therapy. SUMMARY: There are promising advances in the treatment approaches, disease activity criteria, clinical guidelines, pharmaceutical choices and individually stratified therapy choices for polyarticular JIA. PMID- 26147757 TI - Neutrophils in pediatric autoimmune disease. AB - PURPOSE OF REVIEW: As first immune responders, neutrophils are essential mediators of host defense, and also contribute to chronic pathologic inflammation at the crossroads of innate and adaptive immunity. In this review, we will highlight the current understanding of the role of neutrophils in pediatric rheumatology, with a focus on juvenile idiopathic arthritis (JIA) and lupus. RECENT FINDINGS: In inflamed tissues, neutrophils extrude neutrophil extracellular traps containing autoantigen that potentially drives lupus and rheumatoid factor-positive JIA. However, the contribution of neutrophil extracellular traps to pathogenesis remains an area of intense investigation. In JIA joints, neutrophils are activated to such an extent that associated circulating levels of S100A proteins may serve as biomarkers, correlating with disease activity, predicting response to treatment and heralding flares. Beyond the effects of 'normal' activation, neutrophils in JIA and lupus display dysregulation in gene expression, subset activation, and apoptosis. SUMMARY: The role of neutrophils in pediatric rheumatology is an understudied area, but garnering increasing attention. Although clearly implicated in JIA and lupus, the specific contributions of neutrophils to pathogenesis and the use of neutrophil activity surrogates as biomarkers require further study. Clarification of these outstanding issues will have implications for diagnosis and treatment of pediatric rheumatologic conditions. PMID- 26147758 TI - HECT E3 Ubiquitin Ligase Itch Functions as a Novel Negative Regulator of Gli Similar 3 (Glis3) Transcriptional Activity. AB - The transcription factor Gli-similar 3 (Glis3) plays a critical role in the generation of pancreatic beta cells and the regulation insulin gene transcription and has been implicated in the development of several pathologies, including type 1 and 2 diabetes and polycystic kidney disease. However, little is known about the proteins and posttranslational modifications that regulate or mediate Glis3 transcriptional activity. In this study, we identify by mass-spectrometry and yeast 2-hybrid analyses several proteins that interact with the N-terminal region of Glis3. These include the WW-domain-containing HECT E3 ubiquitin ligases, Itch, Smurf2, and Nedd4. The interaction between Glis3 and the HECT E3 ubiquitin ligases was verified by co-immunoprecipitation assays and mutation analysis. All three proteins interact through their WW-domains with a PPxY motif located in the Glis3 N-terminus. However, only Itch significantly contributed to Glis3 polyubiquitination and reduced Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 required the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Transcription analyses demonstrated that Itch dramatically inhibited Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover. Taken together, our study identifies Itch as a critical negative regulator of Glis3-mediated transcriptional activity. This regulation provides a novel mechanism to modulate Glis3-driven gene expression and suggests that it may play a role in a number of physiological processes controlled by Glis3, such as insulin transcription, as well as in Glis3-associated diseases. PMID- 26147759 TI - The Effects of Platelet-Rich Plasma on Halting the Progression in Porcine Intervertebral Disc Degeneration. AB - Disc degeneration and the subsequent herniation and/or rupture of the intervertebral disc (IVD) are due to a failure of the extracellular matrix of the annulus to contain the contents of the nucleus. This results from inadequate maintenance of the matrix components as well as the proteolytic activity of matrix metalloproteinases (MMPs) that degrade matrix molecules. Arresting progression of disc degeneration in the annulus holds greater clinical potential at this point than prevention of its onset in the nucleus. Therefore, in this study, we have therapeutic aims that would decrease levels of the cytokines and growth factors that indirectly lead to disc degeneration via stimulating MMP and increase levels of several beneficial growth factors, such as transforming growth factor-beta, with the addition of platelet-rich plasma (PRP) that would stimulate cell growth and matrix synthesis. For this study, we attempted to address these imbalances of metabolism by using tumor necrosis factor-alpha treated annulus fibrosus cells isolated from porcine IVD tissue and incubating the cells in a growth factor rich environment with PRP. These results indicate that the PRP in vitro increased the production of the major matrix components (type II collagen and aggrecan) and decreased the inhibitory collagenase MMP-1. This application will address a therapeutic approach for intervening early in the degenerative process. PMID- 26147760 TI - Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. AB - Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14 15 degrees C) increased peripheral insulin sensitivity by ~43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, without effects on insulin signaling or AMP-activated protein kinase (AMPK) activation and only a minor increase in BAT glucose uptake. PMID- 26147761 TI - beta2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. AB - Aging drives cognitive and regenerative impairments in the adult brain, increasing susceptibility to neurodegenerative disorders in healthy individuals. Experiments using heterochronic parabiosis, in which the circulatory systems of young and old animals are joined, indicate that circulating pro-aging factors in old blood drive aging phenotypes in the brain. Here we identify beta2 microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. B2M is elevated in the blood of aging humans and mice, and it is increased within the hippocampus of aged mice and young heterochronic parabionts. Exogenous B2M injected systemically, or locally in the hippocampus, impairs hippocampal dependent cognitive function and neurogenesis in young mice. The negative effects of B2M and heterochronic parabiosis are, in part, mitigated in the hippocampus of young transporter associated with antigen processing 1 (Tap1)-deficient mice with reduced cell surface expression of MHC I. The absence of endogenous B2M expression abrogates age-related cognitive decline and enhances neurogenesis in aged mice. Our data indicate that systemic B2M accumulation in aging blood promotes age-related cognitive dysfunction and impairs neurogenesis, in part via MHC I, suggesting that B2M may be targeted therapeutically in old age. PMID- 26147762 TI - Structural Rigidity and Protein Thermostability in Variants of Lipase A from Bacillus subtilis. AB - Understanding the origin of thermostability is of fundamental importance in protein biochemistry. Opposing views on increased or decreased structural rigidity of the folded state have been put forward in this context. They have been related to differences in the temporal resolution of experiments and computations that probe atomic mobility. Here, we find a significant (p = 0.004) and fair (R2 = 0.46) correlation between the structural rigidity of a well characterized set of 16 mutants of lipase A from Bacillus subtilis (BsLipA) and their thermodynamic thermostability. We apply the rigidity theory-based Constraint Network Analysis (CNA) approach, analyzing directly and in a time independent manner the statics of the BsLipA mutants. We carefully validate the CNA results on macroscopic and microscopic experimental observables and probe for their sensitivity with respect to input structures. Furthermore, we introduce a robust, local stability measure for predicting thermodynamic thermostability. Our results complement work that showed for pairs of homologous proteins that raising the structural stability is the most common way to obtain a higher thermostability. Furthermore, they demonstrate that related series of mutants with only a small number of mutations can be successfully analyzed by CNA, which suggests that CNA can be applied prospectively in rational protein design aimed at higher thermodynamic thermostability. PMID- 26147765 TI - Model to predict inpatient mortality from information gathered at presentation to an emergency department: The Triage Information Mortality Model (TIMM). AB - OBJECTIVES: To derive and validate a mortality prediction model from information available at ED triage. METHODS: Multivariable logistic regression of variables from administrative datasets to predict inpatient mortality of patients admitted through an ED. Accuracy of the model was assessed using the receiver operating characteristic area under the curve (ROC-AUC) and calibration using the Hosmer Lemeshow goodness of fit test. The model was derived, internally validated and externally validated. Derivation and internal validation were in a tertiary referral hospital and external validation was in an urban community hospital. RESULTS: The ROC-AUC for the derivation set was 0.859 (95% CI 0.856-0.865), for the internal validation set was 0.848 (95% CI 0.840-0.856) and for the external validation set was 0.837 (95% CI 0.823-0.851). Calibration assessed by the Hosmer Lemeshow goodness of fit test was good. CONCLUSIONS: The model successfully predicts inpatient mortality from information available at the point of triage in the ED. PMID- 26147763 TI - Improved informed consent documents for biomedical research do not increase patients' understanding but reduce enrolment: a study in real settings. AB - AIMS: The aim was to evaluate the comprehension of participants of an improved informed consent document (ICD). METHOD: This was a randomized controlled French multicentre study performed in real conditions. Participants were adult patients undergoing screening for enrolment in biomedical research studies, who agreed to answer a validated questionnaire evaluating objective and subjective comprehension scored from 0 (no comprehension) to 100 (excellent comprehension). Patients were provided either the original ICD or an ICD modified in terms of structure and readability. The primary end point was the score of objective comprehension. The secondary end-points were the enrolment rate in the clinical study and patient characteristics associated with the score of objective comprehension. RESULTS: Four hundred and eighty-one patients were included, 241 patients in the original ICD group and 240 patients in the modified ICD group. There was no difference between the two groups for the score of objective comprehension (original ICD 72.7 (95% CI 71.3, 74.1) vs. modified ICD 72.5 (95% CI 71.0, 74.0); P = 0.81). However, the rate of enrolment in the clinical study was lower in the group who received the modified ICD (64.4% (95% CI 58.3, 70.5)) than for the original ICD (73.0% (95% CI 67.4, 78.7)) (P = 0.042). Only female gender and high educational level were associated with a better objective comprehension. CONCLUSIONS: Improving ICDs had no effect on participants' understanding, whereas the rate of enrolment was lower in this group. In attempts at improving potential participants' understanding of clinical research information, efforts and future trials should focus on other ways to improve comprehension. PMID- 26147764 TI - A histomorphometric assessment of collagen-stabilized anorganic bovine bone mineral in maxillary sinus augmentation - a randomized controlled trial in sheep. AB - OBJECTIVE: To histomorphometrically compare the use of collagen-stabilized anorganic bovine bone (ABBM-C) (test) to anorganic bovine bone + autogenous bone (ABBM + AB) (control) in maxillary sinus augmentation. MATERIALS AND METHODS: Nine sheep underwent bilateral sinus augmentation. Each sinus was randomized to receive either control or test bone graft. Three animals were sacrificed at 8 weeks, and six animals were sacrificed at 16 weeks post-grafting. The 18 sinuses were processed for histomorphometry, which assessed the area fraction of new bone (%NB), residual graft (%RG) and soft tissue components (% STM), as well as graft particle osseointegration (% OI), within three zones equally distributed from the augmented sinus floor. RESULTS: At week 16, a significant increase in %NB was evident across all three zones in the control group when compared to week 8. A significantly greater %NB was evident in the control group when compared to the test group in zones 2 (P < 0.001) and 3 (P < 0.001). There was a significant increase in %OI in week 16 when compared to week 8 across all three zones in the control group (P < 0.001). %OI in the control group was significantly greater across all three zones when compared to the test group at week 16 (P < 0.001). Zone was found to be a significant main effect (P < 0.001) that was independent of time and treatment with decreasing %OI in distant zones. %RG did not significantly change with time for both groups. There was a significant reduction in %ST in week 16 when compared to week 8 across all three zones in the control group (P < 0.001). %ST in the test group was significantly greater across all zones when compared to the control group at week 16 (P < 0.001). CONCLUSION: Both groups exhibited very similar histomorphometric measurements in the zones proximal to the resident sinus wall. The % NB and % OI were greatest in the zones proximal to resident bony walls and gradually decreased as the distance from the proximal walls increased. There was greater % NB and % OI in the control group when compared to the test group in the distant zone. PMID- 26147766 TI - Preference and avoidance pH of brook trout Salvelinus fontinalis and brown trout Salmo trutta exposed to different holding pH. AB - The goal of this study was to determine if short-term exposure of brook trout Salvelinus fontinalis and brown trout Salmo trutta to a lower pH than found in their source stream results in a shift in preference or avoidance pH. The lack of a shift in preference or avoidance pH of adult S. fontinalis and S. trutta suggests that these species can be held at a pH different from the source waterbody for a short period of time without altering preference or avoidance pH behaviour. PMID- 26147767 TI - PPI versus Histamine H2 Receptor Antagonists for Prevention of Upper Gastrointestinal Injury Associated with Low-Dose Aspirin: Systematic Review and Meta-analysis. AB - This study compared proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2RAs) for prevention of low-dose aspirin (LDA)-related gastrointestinal (GI) erosion, ulcer and bleeding. Electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Data were searched from the date of their establishment to December 31, 2013. Randomized controlled trials comparing PPIs and H2RAs for prevention of GI injury associated with low-dose aspirin (LDA) were collected. Two reviewers independently abstracted studies and patient characteristics and appraised study quality using the Cochrane risk-of-bias tool. Meta-analysis was performed using RevMan 5.1 software. We included nine RCTs involving 1047 patients. The meta analysis showed that PPIs were superior to H2RAs for prevention of LDA-associated GI erosion/ulcer [odds ratio (OR=0.28, 95% confidence interval (CI): 0.16-0.50] and bleeding (OR=0.28, 95% CI: 0.14-0.59). In conclusion, PPIs were superior to H2RAs for prevention of LDA-related GI erosion/ulcer and bleeding. Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs. PMID- 26147768 TI - Influence of the rs738409 polymorphism in patatin-like phospholipase 3 on the treatment efficacy of non-alcoholic fatty liver disease with type 2 diabetes mellitus. AB - AIM: A genome-wide association study revealed that the single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with non-alcoholic fatty liver disease (NAFLD). Recent pilot studies investigated the effects of dipeptidyl peptidase-4 inhibitors on liver function and glucose metabolism in NAFLD with type 2 diabetes mellitus (DM). We herein evaluated the efficacy of alogliptin in NAFLD patients with type 2 DM as well as the relationship between genotypes at rs738409 in PNPLA3 and treatment efficacy. METHODS: Forty-one biopsy-proven NAFLD patients with type 2 DM treated with 25 mg/day alogliptin were retrospectively enrolled. SNP rs738409 in PNPLA3 was present in all patients. Clinical data were measured before and after the treatment. RESULTS: Average hemoglobin A1c (HbA1c) levels mostly remained unchanged. Moreover, significant changes were not noted in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) during the follow-up period. A positive correlation was observed between improvements in HbA1c (DeltaHbA1c) levels and changes in AST (DeltaAST) and ALT (DeltaALT) levels (r = 0.325 and 0.439, respectively). Patients with the risk allele (G-allele) showed more positive correlation between DeltaHbA1c and changes in transaminase. Furthermore, improvements in the levels of total cholesterol, triglycerides and hyaluronic acid were significantly greater in G-allele patients in the weight loss group. CONCLUSION: The treatment of NAFLD with type 2 DM with alogliptin contributed to the amelioration of NAFLD. Our results suggested that differences in the PNPLA3 risk allele affected the therapeutic effects of this treatment. PMID- 26147769 TI - Assorted Processing of Synthetic Trans-Acting siRNAs and Its Activity in Antiviral Resistance. AB - The use of syn-tasiRNAs has been proposed as an RNA interference technique alternative to those previously described: hairpin based, virus induced gene silencing or artificial miRNAs. In this study we engineered the TAS1c locus to impair Plum pox virus (PPV) infection by replacing the five native siRNAs with two 210-bp fragments from the CP and the 3'NCR regions of the PPV genome. Deep sequencing analysis of the small RNA species produced by both constructs in planta has shown that phased processing of the syn-tasiRNAs is construct specific. While in syn-tasiR-CP construct the processing was as predicted 21-nt phased in register with miR173-guided cleavage, the processing of syn-tasiR-3NCR is far from what was expected. A 22-nt species from the miR173-guided cleavage was a guide of two series of phased small RNAs, one of them in an exact 21-nt register, and the other one in a mixed of 21-/22-nt frame. In addition, both constructs produced abundant PPV-derived small RNAs in the absence of miR173 as a consequence of a strong sense post-transcriptional gene silencing induction. The antiviral effect of both constructs was also evaluated in the presence or absence of miR173 and showed that the impairment of PPV infection was not significantly higher when miR173 was present. The results show that syn-tasiRNAs processing depends on construct-specific factors that should be further studied before the so-called MIGS (miRNA-induced gene silencing) technology can be used reliably. PMID- 26147770 TI - Comparing the Performance of the S-TOFHLA and NVS Among and Between English and Spanish Speakers. AB - Given the growing body of evidence demonstrating the significant implications of health literacy on a myriad of outcomes, researchers continue to incorporate health literacy metrics in studies. With this proliferation in measurement of health literacy in research, it has become increasingly important to understand how various health literacy tools perform in specific populations. Our objective was to compare the performance of two widely used tests, the Short Test of Functional Health Literacy in Adults (S-TOFHLA) and the Newest Vital Sign (NVS) among and between a sample of English and Spanish-speaking patients. Adults (N = 402) ages 50-75 years participating in a trial to promote colorectal cancer screening completed in-person interviews which included both measures of health literacy. In the full sample, the tests were moderately correlated (r = 0.69, p < .0001); however, there was a stronger correlation among those completing the test in Spanish (r = 0.83) as compared with English (r = 0.58, p < .0001). English speakers more often were categorized as having adequate literacy by the S-TOFHLA as compared with the NVS, whereas Spanish speakers scored consistently low on both instruments. These findings indicate that the categorization of participants into levels of literacy is likely to vary, depending on whether the NVS or S TOFHLA is used for assessment, a factor which researchers should be aware of when selecting literacy assessments. PMID- 26147771 TI - In Vivo Demonstration of Addressable Microstimulators Powered by Rectification of Epidermically Applied Currents for Miniaturized Neuroprostheses. AB - Electrical stimulation is used in order to restore nerve mediated functions in patients with neurological disorders, but its applicability is constrained by the invasiveness of the systems required to perform it. As an alternative to implantable systems consisting of central stimulation units wired to the stimulation electrodes, networks of wireless microstimulators have been devised for fine movement restoration. Miniaturization of these microstimulators is currently hampered by the available methods for powering them. Previously, we have proposed and demonstrated a heterodox electrical stimulation method based on electronic rectification of high frequency current bursts. These bursts can be delivered through textile electrodes on the skin. This approach has the potential to result in an unprecedented level of miniaturization as no bulky parts such as coils or batteries are included in the implant. We envision microstimulators designs based on application-specific integrated circuits (ASICs) that will be flexible, thread-like (diameters < 0.5 mm) and not only with controlled stimulation capabilities but also with sensing capabilities for artificial proprioception. We in vivo demonstrate that neuroprostheses composed of addressable microstimulators based on this electrical stimulation method are feasible and can perform controlled charge-balanced electrical stimulation of muscles. We developed miniature external circuit prototypes connected to two bipolar probes that were percutaneously implanted in agonist and antagonist muscles of the hindlimb of an anesthetized rabbit. The electronic implant architecture was able to decode commands that were amplitude modulated on the high frequency (1 MHz) auxiliary current bursts. The devices were capable of independently stimulating the target tissues, accomplishing controlled dorsiflexion and plantarflexion joint movements. In addition, we numerically show that the high frequency current bursts comply with safety standards both in terms of tissue heating and unwanted electro-stimulation. We demonstrate that addressable microstimulators powered by rectification of epidermically applied currents are feasible. PMID- 26147772 TI - Depressive symptoms, social support, and violence exposure among urban youth: A longitudinal study of resilience. AB - Depression is a serious mental health concern among adolescents. Violence exposure is a potent risk factor for depression. Social support may help reduce depression risk, even when adolescents are exposed to violence. Using a compensatory model of resilience, we investigate the influence of violence exposure and social support on depression over time in a sample of urban youth during the high school years (N = 824, 52% female, mean age Year 1 = 14.9). We used growth curve modeling to examine depressive symptoms across adolescence and its association with violence exposure and social support, accounting for important sociodemographic characteristics (sex, socioeconomic status, and race/ethnicity). Depressive symptoms on average increase from Year 1 to 2 of high school and then are stable or decline from Years 2 to 4. Violence observation and conflict in the family were each associated with increased depressive symptoms during the high school years. Mother support was associated with decreased depressive symptoms over time. Our results support a compensatory model of resilience. Promoting positive parent-child communication among urban youth living in disadvantaged contexts may help reduce the probability that exposure to violence will result in depressive symptoms. PMID- 26147773 TI - Identifying developmental cascades among differentiated dimensions of social competence and emotion regulation. AB - This study used data from 356 children, their mothers, teachers, and peers to examine the longitudinal and dynamic associations among 3 dimensions of social competence derived from Hinde's (1987) framework of social complexity: social skills, peer group acceptance, and friendship quality. Direct and indirect associations among each discrete dimension of social competence and emotion regulation were also examined. The results suggest that there are important distinctions among the dimensions of social competence as they relate to one another and to emotion regulation. Model comparisons provided evidence of cascading and reciprocal effects among the variables, demonstrating complex associations that are ongoing across middle childhood. Specifically, there were cascading effects from emotion regulation abilities at age 5 years to social skills at age 7, which was then associated with age 10 outcomes of more positive friendship quality, greater peer acceptance, and greater emotion regulation. PMID- 26147774 TI - Secure base representations in middle childhood across two Western cultures: Associations with parental attachment representations and maternal reports of behavior problems. AB - Recent work examining the content and organization of attachment representations suggests that 1 way in which we represent the attachment relationship is in the form of a cognitive script. This work has largely focused on early childhood or adolescence/adulthood, leaving a large gap in our understanding of script-like attachment representations in the middle childhood period. We present 2 studies and provide 3 critical pieces of evidence regarding the presence of a script-like representation of the attachment relationship in middle childhood. We present evidence that a middle childhood attachment script assessment tapped a stable underlying script using samples drawn from 2 western cultures, the United States (Study 1) and Belgium (Study 2). We also found evidence suggestive of the intergenerational transmission of secure base script knowledge (Study 1) and relations between secure base script knowledge and symptoms of psychopathology in middle childhood (Study 2). The results from this investigation represent an important downward extension of the secure base script construct. PMID- 26147775 TI - Student characteristics and behaviors at age 12 predict occupational success 40 years later over and above childhood IQ and parental socioeconomic status. AB - Drawing on a 2-wave longitudinal sample spanning 40 years from childhood (age 12) to middle adulthood (age 52), the present study was designed to examine how student characteristics and behaviors in late childhood (assessed in Wave 1 in 1968) predict career success in adulthood (assessed in Wave 2 in 2008). We examined the influence of parental socioeconomic status (SES), childhood intelligence, and student characteristics and behaviors (inattentiveness, school entitlement, responsible student, sense of inferiority, impatience, pessimism, rule breaking and defiance of parental authority, and teacher-rated studiousness) on 2 important real-life outcomes (i.e., occupational success and income). The longitudinal sample consisted of N = 745 persons who participated in 1968 (M = 11.9 years, SD = 0.6; 49.9% female) and 2008 (M = 51.8 years, SD = 0.6; 53.3% female). Regression analyses and path analyses were conducted to evaluate the direct and indirect effects (via education) of the predictors on career success. The results revealed direct and indirect influences of student characteristics (responsible student, rule breaking and defiance of parental authority, and teacher-rated studiousness) across the life span on career success after adjusting for differences in parental SES and IQ at age 12. rd PMID- 26147776 TI - Longitudinal relations between prosocial television content and adolescents' prosocial and aggressive behavior: The mediating role of empathic concern and self-regulation. AB - The current study examined longitudinal cross-lagged associations between prosocial TV (content and time) and prosocial and aggressive behavior during adolescence, and explored the mediating role of empathic concern and self regulation. Participants were 441 adolescents who reported on their 3 favorite TV shows at 2 time points, approximately 2 years apart (M age of child at Time 3 = 13.31, SD = 1.06; 52% female; M age of child at Time 5 = 15.27, SD = 1.06). Results suggested that prosocial content at Time 3 was negatively associated with aggressive behavior 2 years later, and aggressive behavior at Time 3 was positively associated with aggressive content 2 years later. Results also suggested that prosocial behavior toward strangers at Time 3 was associated with both empathic concern and self-regulation at Time 4, which were in turn associated with prosocial and aggressive content at Time 5. Discussion focuses on the important role of behavior and prosocial personality on media selection during adolescence and the relevance of the target of prosocial behavior. PMID- 26147777 TI - Children show heightened knew-it-all-along errors when learning new facts about kinds: Evidence for the power of kind representations in children's thinking. AB - Several proposals in the literature on conceptual development converge on the claim that information about kinds of things in the world has a privileged status in children's cognition, insofar as it is acquired, manipulated, and stored with surprising ease. Our goal in the present studies (N = 440) was to test a prediction of this claim. Specifically, if the early cognitive system privileges kind (or generic) information in the proposed ways, then learning new facts about kinds should be so seamless that it is often accompanied by an impression that these facts were known all along. To test this prediction, we presented 4- to 7 year-old children with novel kind-wide and individual-specific facts, and we then asked children whether they had prior knowledge of these facts. As predicted, children were under the impression that they had known the kind-wide facts more often than the individual-specific facts, even though in reality they had just learned both (Experiments 1, 2, 3, and 5). Importantly, learning facts about (nongeneric) plural sets of individuals was not similarly accompanied by heightened knew-it-all-along errors (Experiment 4), highlighting the privileged status of kind information per se. Finally, we found that young children were able to correctly recognize their previous ignorance of newly learned generic facts when this ignorance was made salient before the learning event (Experiment 6), suggesting that children's frequent knew-it-all-along impressions about such facts truly stem from metacognitive difficulties rather than being a methodological artifact. In sum, these 6 studies indicate that learning information about kinds is accompanied by heightened knew-it-all-along errors. More broadly, this evidence supports the view that early cognition privileges kind representations. PMID- 26147778 TI - Oral lichen planus: an update on its pathogenesis. AB - Oral lichen planus (OLP) is a common T cell-mediated mucocutaneous disease of unknown etiology. A great number of factors have been suggested as relevant to the etiology of this disease. In this article, the authors assemble recent knowledge about the pathogenesis of OLP, discuss some proposed hypotheses, and compare OLP with oral lichenoid lesions. PMID- 26147779 TI - Correction: Prevalence and Transmission of Trypanosoma cruzi in People of Rural Communities of the High Jungle of Northern Peru. PMID- 26147780 TI - Metabolic shifts induced by human H460 cells in tumor-bearing mice. AB - Tumor markers are most popularly used in diagnosis of various cancers clinically. However, the confounding factors of individual background diversities, such as genetics, food preferences, living styles, physical exercises, etc., greatly challenge the identification of tumor markers. Study of the metabolic impact of inoculated tumors on model animals can facilitate the identification of metabolomic markers relevant to tumor insult. In this study, serum metabolites from nude mice (n = 14) inoculated with human H460 cells (human nonsmall cell lung carcinoma) were profiled using gas chromatography time-of-flight mass spectrometry. The mice with inoculated tumors showed an obviously different metabolic pattern from the control; identification of the discriminatory metabolites suggested the metabolic perturbation of free fatty acids, amino acids, glycolysis and tricarboxylic acid (TCA) cycle turnover. The significantly decreased TCA intermediates, free fatty acids, 3-hydroxybutyric acid and fluctuating amino acids (t-test, p < 0.05) in serum of tumor-bearing mice characterized the metabolic impact of local inoculated H460 tumor cells on the whole system. This indicates that they are candidate metabolomic markers for translational study of lung cancer, clinically. PMID- 26147781 TI - Stereoselective Electrophilic Cyclization. AB - Electrophilic cyclizations of unactivated alkenes play highly important roles in the synthesis of useful building blocks. This account describes our contributions to the rational design of monofunctionalized chiral Lewis base catalysts for enantioselective iodo- and protocyclizations. For the stereoselective promotion of electrophilic bromocyclizations, nucleophilic phosphite-urea cooperative catalysts have been designed. PMID- 26147782 TI - Religion, assessment and the problem of 'normative uncertainty' for mental health student nurses: a critical incident-informed qualitative interview study. AB - There is limited research around how mental health (MH) student nurses interpret and differentiate between people's religious and cultural beliefs and the existence of psychopathological symptomatology and experiences. Here we focus on one cultural issue that arose from research exploring how MH student nurses approach and interpret religion and culture in their practice - that is, the difficulties in determining the clinical significance of the religious beliefs and experiences expressed by the people they care for. While problems with establishing the cultural boundaries of normality in clinical assessments are an important area of debate in cultural psychiatry, it remains a peripheral issue in MH nurse education. An anthropologically informed qualitative research design underpinned 'critical incident' (CI)-focused ethnographic interviews with 36 second and third-year MH nursing field students and seven undergraduate MH branch lecturers. Follow up focus groups were also carried out. Interview transcripts were subject to thematic analysis. Four subthemes were identified under the broad theme of the clinical significance of religious-type expression and experience: (1) identifying the difference between delusions and religious belief; (2) identifying whether an experience was hallucination or religious experience; (3) the clinical implications of such challenges; and (4) applying religion-specific knowledge. There are clinical implications that may result from the difficulties with assessing the clinical significance of religious beliefs and experiences, identified in both our research and within international cultural psychiatry literature and research. Misinterpretation and therefore wrongly assessing someone's experience as pathological is a significant concern. It is suggested that CI analysis could be adapted to help nurses, nursing students and nurse educators recognize the religious dimensions of mental distress, particularly those that then potentially impact upon the accuracy and person centeredness of clinical assessment. Further research is proposed to investigate the clinical assessment and training needs of nurses in the area of religion and mental distress. PMID- 26147783 TI - Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening. AB - Characteristics of inhibitors identified by prospective screening may differ from those detected clinically. In a prospective study at 17 hemophilia centers with central inhibitor measurement by Nijmegen-Bethesda assay, 23 (2.8%) of 824 hemophilia A patients had new inhibitors detected: nine high-titer inhibitors (HTI: 7 >= 5.0 NBU plus 2 of 2.6 and 3.4 NBU at immune tolerance induction initiation) and 14 low-titer inhibitors (LTI: 0.5-1.9 NBU). HTI occurred at an earlier age (median 2 years, range 1-18, vs. median 11 years, range 2-61, P = 0.016). Both HTI (22%) and LTI (43%) occurred in non-severe patients. All HTI, but only 64% of LTI, were found to be FVIII-specific by chromogenic Bethesda assay or fluorescence immunoassay (FLI), indicating a high rate of false-positive LTI. Repeat specimens confirmed all HTI, 7/9 LTI, and 7/7 FVIII-specific LTI. FLI results were similar between HTI and FVIII-specific LTI; all included IgG1 and IgG4 subclasses. A comparable prospective study conducted from 1975 to 1979 at 13 U.S. centers found 31 (2.4%) new inhibitors among 1,306 patients. In both studies, one-third of inhibitors occurred in non-severe patients and one-quarter after 150 exposure days (ED). Significant differences were seen in the age at which inhibitors occurred (median 16 years in the older study vs. 5 years currently, P = 0.024) and in ED before inhibitor development, 10% in the older study and 43% currently study occurring within 20 ED, suggesting a temporal change in inhibitor development. Prospective screening detects inhibitors in patients of all severities, ages, and ED. Some LTI, however, are false positives. PMID- 26147784 TI - Intra-adrenal Aldosterone Secretion: Segmental Adrenal Venous Sampling for Localization. AB - PURPOSE: To use segmental adrenal venous sampling (AVS) (S-AVS) of effluent tributaries (a version of AVS that, in addition to helping identify aldosterone hypersecretion, also enables the evaluation of intra-adrenal hormone distribution) to detect and localize intra-adrenal aldosterone secretion. MATERIALS AND METHODS: The institutional review board approved this study, and all patients provided informed consent. S-AVS was performed in 65 patients with primary aldosteronism (34 men; mean age, 50.9 years +/- 11 [standard deviation]). A microcatheter was inserted in first-degree tributary veins. Unilateral aldosterone hypersecretion at the adrenal central vein was determined according to the lateralization index after cosyntropin stimulation. Excess aldosterone secretion at the adrenal tributary vein was considered to be present when the aldosterone/cortisol ratio from this vein exceeded that from the external iliac vein; suppressed secretion was indicated by the opposite pattern. Categoric variables were expressed as numbers and percentages; continuous variables were expressed as means +/- standard errors of the mean. RESULTS: The AVS success rate, indicated by a selectivity index of 5 or greater, was 98% (64 of 65). The mean numbers of sampled tributaries on the left and right sides were 2.11 and 1.02, respectively. The following diagnoses were made on the basis of S-AVS results: unilateral aldosterone hypersecretion in 30 patients, bilateral hypersecretion without suppressed segments in 22 patients, and bilateral hypersecretion with at least one suppressed segment in 12 patients. None of the patients experienced severe complications. CONCLUSION: S-AVS could be used to identify heterogeneous intra-adrenal aldosterone secretion. Patients who have bilateral aldosterone-producing adenomas can be treated with adrenal-sparing surgery or other minimally invasive local therapies if any suppressed segment is identified at S-AVS. PMID- 26147785 TI - An echo-planar imaging sequence is superior to a steady-state free precession sequence for visual as well as quantitative assessment of cardiac magnetic resonance stress perfusion. AB - BACKGROUND: To assess myocardial perfusion, steady-state free precession cardiac magnetic resonance (SSFP, CMR) was compared with gradient-echo-echo-planar imaging (GRE-EPI) using myocardial perfusion scintigraphy (MPS) as reference. METHODS: Cardiac magnetic resonance perfusion was recorded in 30 patients with SSFP and in another 30 patients with GRE-EPI. Timing and extent of inflow delay to the myocardium was visually assessed. Signal-to-noise (SNR) and contrast-to noise (CNR) ratios were calculated. Myocardial scar was visualized with a phase sensitive inversion recovery sequence (PSIR). All scar positive segments were considered pathologic. In MPS, stress and rest images were used as in clinical reporting. The CMR contrast wash-in slope was calculated and compared with the stress score from the MPS examination. CMR scar, CMR perfusion and MPS were assessed separately by one expert for each method who was blinded to other aspects of the study. RESULTS: Visual assessment of CMR had a sensitivity for the detection of an abnormal MPS at 78% (SSFP) versus 91% (GRE-EPI) and a specificity of 58% (SSFP) versus 84% (GRE-EPI). Kappa statistics for SSFP and MPS was 0.29, for GRE-EPI and MPS 0.72. The ANOVA of CMR perfusion slopes for all segments versus MPS score (four levels based on MPS) had correlation r = 0.64 (SSFP) and r = 0.96 (GRE-EPI). SNR was for normal segments 35.63 +/- 11.80 (SSFP) and 17.98 +/ 8.31 (GRE-EPI), while CNR was 28.79 +/- 10.43 (SSFP) and 13.06 +/- 7.61 (GRE EPI). CONCLUSION: GRE-EPI displayed higher agreement with the MPS results than SSFP despite significantly lower signal intensity, SNR and CNR. PMID- 26147786 TI - Continuous Processing of Active Pharmaceutical Ingredients Suspensions via Dynamic Cross-Flow Filtration. AB - Over the last years, continuous manufacturing has created significant interest in the pharmaceutical industry. Continuous filtration at low flow rates and high solid loadings poses, however, a significant challenge. A commercially available, continuously operating, dynamic cross-flow filtration device (CFF) is tested and characterized. It is shown that the CFF is a highly suitable technology for continuous filtration. For all tested model active pharmaceutical ingredients, a material-specific strictly linear relationship between feed and permeate rate is identified. Moreover, for each tested substance, a constant concentration factor is reached. A one-parameter model based on a linear equation is suitable to fully describe the CFF filtration performance. This rather unexpected finding and the concentration polarization layer buildup is analyzed and a basic model to describe the observed filtration behavior is developed. PMID- 26147787 TI - Polydopamine-graphene oxide derived mesoporous carbon nanosheets for enhanced oxygen reduction. AB - Composite materials combining nitrogen-doped carbon (NC) with active species represent a paramount breakthrough as alternative catalysts to Pt for the oxygen reduction reaction (ORR) due to their competitive activity, low cost and excellent stability. In this paper, a simple strategy is presented to construct graphene oxide-polydopamine (GD) based carbon nanosheets. This approach does not need to modify graphene and use any catalyst for polymerization under ambient conditions, and the obtained carbon nanosheets possess adjustable thicknesses and uniform mesoporous structures without using any template. The thickness of GD hybrids and the carbonization temperature are found to play crucial roles in adjusting the microstructure of the resulting carbon nanosheets and, accordingly their ORR catalytic activity. The optimized carbon nanosheet generated by a GD hybrid of 5 nm thickness after 900 degrees C carbonization exhibits superior ORR activity with an onset potential of -0.07 V and a kinetic current density of 13.7 mA cm(-2) at -0.6 V. The unique mesoporous structure, high surface areas, abundant defects and favorable nitrogen species are believed to significantly benefit the ORR catalytic process. Furthermore, it also shows remarkable durability and excellent methanol tolerance outperforming those of commercial Pt/C. In view of the physicochemical versatility and structural tunability of polydopamine (PDA) materials, our work would shed new light on the understanding and further development of PDA-based carbon materials for highly efficient electrocatalysts. PMID- 26147788 TI - Lymphomatosis Cerebri: A Diagnostic Challenge. PMID- 26147789 TI - Reaction of Phthalocyanines with Graphene on Ir(111). AB - Iron phthalocyanine (FePc) is adsorbed to graphene on Ir(111) at cryogenic temperature. In addition to mobile FePc with four lobes, imaging and spectroscopy with a scanning tunneling microscope reveal immobile molecules that exhibit fewer lobes. A reversible transformation between four- and three-lobed molecules has been induced by current injection. The data are consistent with chemical bonding of lobes to graphene on Ir, pinning down the graphene area toward Ir. Similar observations are made from NiPc, CoPc, CuPc, and H2Pc. The experimental findings can be explained by ab initio calculations, which suggest that a Diels-Alder-type reaction may be involved with an allyl unit of graphene in the top-fcc moire registry. PMID- 26147791 TI - The effects of intense pulsed light in a mouse model of skin carcinogenesis. PMID- 26147790 TI - Association between drug-specific indicators of prescribing quality and quality of drug treatment: a validation study. AB - PURPOSE: To evaluate the concurrent validity of three European sets of drug specific indicators of prescribing quality METHODS: In 200 hip fracture patients (>=65 years), consecutively recruited to a randomized controlled study in Sahlgrenska University Hospital in 2009, quality of drug treatment at study entry was assessed according to a gold standard as well as to three drug-specific indicator sets (Swedish National Board of Health and Welfare, French consensus panel list, and German PRISCUS list). As gold standard, two specialist physicians independently assessed and then agreed on the quality for each patient, after initial screening with STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) and START (Screening Tool to Alert to Right Treatment). RESULTS: According to the Swedish, French, and German indicator sets, 82 (41%), 54 (27%), and 43 (22%) patients had potentially inappropriate drug treatment. A total of 141 (71%) patients had suboptimal drug treatment according to the gold standard. The sensitivity for the indicator sets was 0.51 (95% confidence interval: 0.43; 0.59), 0.33 (0.26; 0.41), and 0.29 (0.22; 0.37), respectively. The specificity was 0.83 (0.72; 0.91), 0.88 (0.77; 0.94), and 0.97 (0.88; 0.99). Suboptimal drug treatment was 2.0 (0.8; 5.3), 1.9 (0.7; 5.1), and 6.1 (1.3; 28.6) times as common in patients with potentially inappropriate drug treatment according to the indicator sets, after adjustments for age, sex, cognition, residence, multi-dose drug dispensing, and number of drugs. CONCLUSIONS: In this setting, the indicator sets had high specificity and low sensitivity. This needs to be considered upon use and interpretation. PMID- 26147792 TI - Theoretical Predictions of C3v Symmetric Three-H-Bridged Noble Gas Compounds NgBeH3BeR, NgBeH3BR(+), and NgBH3BR(2). AB - A new series of stable noble gas-Lewis acid compounds NgBeH3BeR, NgBeH3BR(+), and NgBH3BR(2+) (R = F, H, CH3, Ng = He-Rn) with three 3c-2e H-bridged bonds have been predicted by use of the PBE0 and MP2 methods. The Ng-Be/B bonds are strong and have large binding energies 35-130, 9-38, and 4-13 kcal/mol for the doubly charged cations, singly charged cations, and neutral molecules, respectively. The binding energy and strength of the Ng-Be/B bonds increase largely from He to Rn but are insensitive to electronegativity of the substituent R. The Ng-B bonds in NgBH3BR(2+) should be typical covalent bonds and the Ng-Be bonds in NgBeH3BR(+) for heavy Ng atoms Kr, Xe, and Rn have some covalent character. The three bridging-H atoms have characteristic infrared vibrational modes with large IR intensity to be detected in spectroscopy experiments. PMID- 26147793 TI - International Intercomparison of Solar UVR Spectral Measurement Systems in Melbourne in 2013. AB - Monitoring ambient solar UVR levels provides information on how much there is in both real time and historically. Quality assurance of ambient measurements of solar UVR is critical to ensuring accuracy and stability and this can be achieved by regular intercomparisons of spectral measurement systems with those of other organizations. In October and November of 2013 a solar UVR spectroradiometer from Public Health England (PHE) was brought to Melbourne for a campaign of intercomparisons with a new Bentham spectrometer of Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) and one at the Australian Bureau of Meteorology (BOM), supported by New Zealand's National Institute for Water and Atmosphere (NIWA). Given all three spectroradiometers have calibrations that are traceable to various national standards, the intercomparison provides a chance to determine measurement uncertainties and traceability that support UV measurement networks in Australia, New Zealand and the UK. UV Index measurements from all three systems were compared and ratios determined for clear sky conditions when the scans from each instrument were within 2 min of each other. While wavelengths below 305 nm showed substantial differences between the PHE unit and the two other systems, overall the intercomparison results were encouraging, with mean differences in measured UV Index between the BOM/NIWA and those of PHE and ARPANSA of <0.1% and 7.5%, respectively. PMID- 26147794 TI - Formation of Halogenated Polyaromatic Compounds by Laccase Catalyzed Transformation of Halophenols. AB - Laccases are a type of extracellular enzyme produced by fungi, bacteria, and plants. Laccase can catalyze one-electron oxidation of a variety of phenolic compounds using molecular oxygen as the electron acceptor. In this study, transformation of halophenols (XPs) in laccase-catalyzed oxidation processes was explored. We first examined the intrinsic reaction kinetics and found that the transformation of XPs appeared first order to the concentrations of both XPs and laccase. A numerical model was developed to describe the role of humic acid (HA) in this process. It was demonstrated that HA could reverse the oxidation of XPs by acting as the inner filtrator of XP radical intermediates formed upon reactions between the substrates and laccase. The extent of such reversion was proportional to HA concentration. MS analysis in combination with quantum chemistry computation suggested that coupling products were generated. XPs coupled to each via C-C or C-O-C pathways, generating hydroxyl polyhalogenated biphenyl ethers (OH-PCDEs) and hydroxyl polyhalogenated biphenyls, respectively. Many of these polyhalogenated products are known to be hazardous to the ecosystem and human health, but they are not synthetic chemicals. This study shed light on their genesis in the environmental media. PMID- 26147795 TI - A de Novo-Designed Monomeric, Compact Three-Helix-Bundle Protein on a Carbohydrate Template. AB - De novo design and chemical synthesis of proteins and of other artificial structures that mimic them is a central strategy for understanding protein folding and for accessing proteins with new functions. We have previously described carbohydrates that act as templates for the assembly of artificial proteins, so-called carboproteins. The hypothesis is that the template preorganizes the secondary structure elements and directs the formation of a tertiary structure, thus achieving structural economy in the combination of peptide, linker, and template. We speculate that the structural information from the template could facilitate protein folding. Here we report the design and synthesis of three-helix-bundle carboproteins on deoxyhexopyranosides. The carboproteins were analyzed by CD, analytical ultracentrifugation (AUC), small angle X-ray scattering (SAXS), and NMR spectroscopy, and this revealed the formation of the first compact and folded monomeric carboprotein, distinctly different from a molten globule. En route to this carboprotein we observed a clear effect originating from the template on protein folding. PMID- 26147796 TI - Calprotectin Increases the Activity of the SaeRS Two Component System and Murine Mortality during Staphylococcus aureus Infections. AB - Calprotectin, the most abundant cytoplasmic protein in neutrophils, suppresses the growth of Staphylococcus aureus by sequestering the nutrient metal ions Zn and Mn. Here we show that calprotectin can also enhance the activity of the SaeRS two component system (TCS), a signaling system essential for production of over 20 virulence factors in S. aureus. The activity of the SaeRS TCS is repressed by certain divalent ions found in blood or neutrophil granules; however, the Zn bound-form of calprotectin relieves this repression. During staphylococcal encounter with murine neutrophils or staphylococcal infection of the murine peritoneal cavity, calprotectin increases the activity of the SaeRS TCS as well as the production of proinflammatory cytokines such as IL-1beta and TNF-alpha, resulting in higher murine mortality. These results suggest that, under certain conditions, calprotectin can be exploited by S. aureus to increase bacterial virulence and host mortality. PMID- 26147797 TI - The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy. AB - Cancer-causing HPV E6 oncoproteins are characterized by the presence of a PDZ binding motif (PBM) at their extreme carboxy terminus. It was long thought that this region of E6 had a sole function to confer interaction with a defined set of cellular substrates. However, more recent studies have shown that the E6 PBM has a complex pattern of regulation, whereby phosphorylation within the PBM can regulate interaction with two classes of cellular proteins: those containing PDZ domains and the members of the 14-3-3 family of proteins. In this review, we explore the roles that the PBM and its ligands play in the virus life cycle, and subsequently how these can inadvertently contribute towards the development of malignancy. We also explore how subtle alterations in cellular signal transduction pathways might result in aberrant E6 phosphorylation, which in turn might contribute towards disease progression. PMID- 26147798 TI - The Use of Non-Variant Sites to Improve the Clinical Assessment of Whole-Genome Sequence Data. AB - Genetic testing, which is now a routine part of clinical practice and disease management protocols, is often based on the assessment of small panels of variants or genes. On the other hand, continuous improvements in the speed and per-base costs of sequencing have now made whole exome sequencing (WES) and whole genome sequencing (WGS) viable strategies for targeted or complete genetic analysis, respectively. Standard WGS/WES data analytical workflows generally rely on calling of sequence variants respect to the reference genome sequence. However, the reference genome sequence contains a large number of sites represented by rare alleles, by known pathogenic alleles and by alleles strongly associated to disease by GWAS. It's thus critical, for clinical applications of WGS and WES, to interpret whether non-variant sites are homozygous for the reference allele or if the corresponding genotype cannot be reliably called. Here we show that an alternative analytical approach based on the analysis of both variant and non-variant sites from WGS data allows to genotype more than 92% of sites corresponding to known SNPs compared to 6% genotyped by standard variant analysis. These include homozygous reference sites of clinical interest, thus leading to a broad and comprehensive characterization of variation necessary to an accurate evaluation of disease risk. Altogether, our findings indicate that characterization of both variant and non-variant clinically informative sites in the genome is necessary to allow an accurate clinical assessment of a personal genome. Finally, we propose a highly efficient extended VCF (eVCF) file format which allows to store genotype calls for sites of clinical interest while remaining compatible with current variant interpretation software. PMID- 26147799 TI - A Stochastic Model to Study Rift Valley Fever Persistence with Different Seasonal Patterns of Vector Abundance: New Insights on the Endemicity in the Tropical Island of Mayotte. AB - Rift Valley fever (RVF) is a zoonotic vector-borne disease causing abortion storms in cattle and human epidemics in Africa. Our aim was to evaluate RVF persistence in a seasonal and isolated population and to apply it to Mayotte Island (Indian Ocean), where the virus was still silently circulating four years after its last known introduction in 2007. We proposed a stochastic model to estimate RVF persistence over several years and under four seasonal patterns of vector abundance. Firstly, the model predicted a wide range of virus spread patterns, from obligate persistence in a constant or tropical environment (without needing vertical transmission or reintroduction) to frequent extinctions in a drier climate. We then identified for each scenario of seasonality the parameters that most influenced prediction variations. Persistence was sensitive to vector lifespan and biting rate in a tropical climate, and to host viraemia duration and vector lifespan in a drier climate. The first epizootic peak was primarily sensitive to viraemia duration and thus likely to be controlled by vaccination, whereas subsequent peaks were sensitive to vector lifespan and biting rate in a tropical climate, and to host birth rate and viraemia duration in arid climates. Finally, we parameterized the model according to Mayotte known environment. Mosquito captures estimated the abundance of eight potential RVF vectors. Review of RVF competence studies on these species allowed adjusting transmission probabilities per bite. Ruminant serological data since 2004 and three new cross-sectional seroprevalence studies are presented. Transmission rates had to be divided by more than five to best fit observed data. Five years after introduction, RVF persisted in more than 10% of the simulations, even under this scenario of low transmission. Hence, active surveillance must be maintained to better understand the risk related to RVF persistence and to prevent new introductions. PMID- 26147801 TI - Making anticoagulation easier and safer in DVT. PMID- 26147800 TI - UV-resistant yeasts isolated from a high-altitude volcanic area on the Atacama Desert as eukaryotic models for astrobiology. AB - The Sairecabur volcano (5971 m), in the Atacama Desert, is a high-altitude extreme environment with high daily temperature variations, acidic soils, intense UV radiation, and low availability of water. Four different species of yeasts were isolated from this region using oligotrophic media, identified and characterized for their tolerance to extreme conditions. rRNA sequencing revealed high identity (>98%) to Cryptococcus friedmannii, Exophiala sp., Holtermanniella watticus, and Rhodosporidium toruloides. To our knowledge, this is the first report of these yeasts in the Atacama Desert. All isolates showed high resistance to UV-C, UV-B and environmental-UV radiation, capacity to grow at moderate saline media (0.75-2.25 mol/L NaCl) and at moderate to cold temperatures, being C. friedmannii and H. watticus able to grow in temperatures down to -6.5 degrees C. The presence of pigments, analyzed by Raman spectroscopy, correlated with UV resistance in some cases, but there is evidence that, on the natural environment, other molecular mechanisms may be as important as pigmentation, which has implications for the search of spectroscopic biosignatures on planetary surfaces. Due to the extreme tolerances of the isolated yeasts, these organisms represent interesting eukaryotic models for astrobiological purposes. PMID- 26147802 TI - PPLine: An Automated Pipeline for SNP, SAP, and Splice Variant Detection in the Context of Proteogenomics. AB - The fundamental mission of the Chromosome-Centric Human Proteome Project (C-HPP) is the research of human proteome diversity, including rare variants. Liver tissues, HepG2 cells, and plasma were selected as one of the major objects for C HPP studies. The proteogenomic approach, a recently introduced technique, is a powerful method for predicting and validating proteoforms coming from alternative splicing, mutations, and transcript editing. We developed PPLine, a Python-based proteogenomic pipeline providing automated single-amino-acid polymorphism (SAP), indel, and alternative-spliced-variants discovery based on raw transcriptome and exome sequence data, single-nucleotide polymorphism (SNP) annotation and filtration, and the prediction of proteotypic peptides (available at https://sourceforge.net/projects/ppline). In this work, we performed deep transcriptome sequencing of HepG2 cells and liver tissues using two platforms: Illumina HiSeq and Applied Biosystems SOLiD. Using PPLine, we revealed 7756 SAP and indels for HepG2 cells and liver (including 659 variants nonannotated in dbSNP). We found 17 indels in transcripts associated with the translation of alternate reading frames (ARF) longer than 300 bp. The ARF products of two genes, SLMO1 and TMEM8A, demonstrate signatures of caspase-binding domain and Gcn5 related N-acetyltransferase. Alternative splicing analysis predicted novel proteoforms encoded by 203 (liver) and 475 (HepG2) genes according to both Illumina and SOLiD data. The results of the present work represent a basis for subsequent proteomic studies by the C-HPP consortium. PMID- 26147803 TI - Colorectal Cancer Screening in Switzerland: Cross-Sectional Trends (2007-2012) in Socioeconomic Disparities. AB - BACKGROUND: Despite universal health care coverage, disparities in colorectal cancer (CRC) screening by income in Switzerland have been reported. However, it is not known if these disparities have changed over time. This study examines the association between socioeconomic position and CRC screening in Switzerland between 2007 and 2012. METHODS: Data from the 2007 (n = 5,946) and 2012 (n = 7,224) population-based Swiss Health Interview Survey data (SHIS) were used to evaluate the association between monthly household income, education, and employment with CRC screening, defined as endoscopy in the past 10 years or fecal occult blood test (FOBT) in the past 2 years. Multivariable Poisson regression was used to estimate prevalence ratios (PR) and 95% Confidence Intervals (CI) adjusting for demographics, health status, and health utilization. RESULTS: CRC screening increased from 18.9% in 2007 to 22.2% in 2012 (padjusted: = 0.036). During the corresponding time period, endoscopy increased (8.2% vs. 15.0%, padjusted:<0.001) and FOBT decreased (13.0% vs. 9.8%, padjusted:0.002). CRC screening prevalence was greater in the highest income (>$6,000) vs. lowest income (<=$2,000) group in 2007 (24.5% vs. 10.5%, PR:1.37, 95%CI: 0.96-1.96) and in 2012 (28.6% vs. 16.0%, PR:1.45, 95%CI: 1.09-1.92); this disparity did not significantly change over time. CONCLUSIONS: While CRC screening prevalence in Switzerland increased from 2007 to 2012, CRC screening coverage remains low and disparities in CRC screening by income persisted over time. These findings highlight the need for increased access to CRC screening as well as enhanced awareness of the benefits of CRC screening in the Swiss population, particularly among low-income residents. PMID- 26147804 TI - SUB1 Plays a Negative Role during Starvation Induced Sporulation Program in Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae Sub1 is involved in several cellular processes such as, transcription initiation, elongation, mRNA processing and DNA repair. It has also been reported to provide cellular resistance during conditions of oxidative DNA damage and osmotic stress. Here, we report a novel role of SUB1 during starvation stress-induced sporulation, which leads to meiosis and spore formation in diploid yeast cells. Deletion of SUB1 gene significantly increased sporulation efficiency as compared to the wild-type cells in S288c genetic background. Whereas, the sporulation functions of the sub1(Y66A) missense mutant were similar to Sub1. SUB1 transcript and protein levels are downregulated during sporulation, in highly synchronized and sporulation proficient wild-type SK1 cells. The changes in Sub1 levels during sporulation cascade correlate with the induction of middle sporulation gene expression. Deletion of SUB1 increased middle sporulation gene transcript levels with no effect on their induction kinetics. In wild-type cells, Sub1 associates with chromatin at these loci in a temporal pattern that correlates with their enhanced gene expression seen in sub1Delta cells. We show that SUB1 genetically interacts with HOS2, which led us to speculate that Sub1 might function with Set3 repressor complex during sporulation. Positive Cofactor 4, human homolog of Sub1, complemented the sub1Delta sporulation phenotype, suggesting conservation of function. Taken together, our results suggest that SUB1 acts as a negative regulator of sporulation. PMID- 26147805 TI - Impact of the Preoperative Controlling Nutritional Status (CONUT) Score on the Survival after Curative Surgery for Colorectal Cancer. AB - BACKGROUND: Recently, the preoperative immune-nutritional status has been reported to correlate with the survival rate in patients with colorectal cancer (CRC). However, there have been no reports on the relationship between the controlling nutritional status (CONUT) score and the clinical outcome after curative surgery for CRC. We herein evaluated the prognostic significance of the CONUT score in patients with CRC, and then compared the accuracy of the CONUT score and the prognostic nutritional index (PNI) as a predictor of survival. METHODS: We retrospectively reviewed a database of 204 patients who underwent curative surgery for Stage II/III CRC. Patients were divided into two groups according to the CONUT score and the PNI. RESULTS: The five-year cancer-specific survival (CSS) rate was significantly higher at 92.7% in the low CONUT group, compared to a rate of 81.0% in the high CONUT group (p=0.0016). The five-year CSS was 71.2% in the low PNI group and 92.3% in the high PNI group, which showed a significant difference (p=0.0155). A multivariate analysis showed that lymph node metastasis and the CONUT score were independent risk factors for CSS. CONCLUSION: This study suggested that the CONUT score is a strong independent predictor of the survival among CRC patients. PMID- 26147807 TI - Analysis of Differentially Expressed Genes Associated with Coronatine-Induced Laticifer Differentiation in the Rubber Tree by Subtractive Hybridization Suppression. AB - The secondary laticifer in the secondary phloem is differentiated from the vascular cambia of the rubber tree (Hevea brasiliensis Muell. Arg.). The number of secondary laticifers is closely related to the rubber yield potential of Hevea. Pharmacological data show that jasmonic acid and its precursor linolenic acid are effective in inducing secondary laticifer differentiation in epicormic shoots of the rubber tree. In the present study, an experimental system of coronatine-induced laticifer differentiation was developed to perform SSH identification of genes with differential expression. A total of 528 positive clones were obtained by blue-white screening, of which 248 clones came from the forward SSH library while 280 clones came from the reverse SSH library. Approximately 215 of the 248 clones and 171 of the 280 clones contained cDNA inserts by colony PCR screening. A total of 286 of the 386 ESTs were detected to be differentially expressed by reverse northern blot and sequenced. Approximately 147 unigenes with an average length of 497 bp from the forward and 109 unigenes with an average length of 514 bp from the reverse SSH libraries were assembled and annotated. The unigenes were associated with the stress/defense response, plant hormone signal transduction and structure development. It is suggested that Ca2+ signal transduction and redox seem to be involved in differentiation, while PGA and EIF are associated with the division of cambium initials for COR-induced secondary laticifer differentiation in the rubber tree. PMID- 26147808 TI - Core-Shell Processing of Natural Pigment: Upper Palaeolithic Red Ochre from Lovas, Hungary. AB - Ochre is the common archaeological term for prehistoric pigments. It is applied to a range of uses, from ritual burials to cave art to medications. While a substantial number of Palaeolithic paint mining pits have been identified across Europe, the link between ochre use and provenance, and their antiquity, has never yet been identified. Here we characterise the mineralogical signature of core shell processed ochre from the Palaeolithic paint mining pits near Lovas in Hungary, using a novel integration of petrographic and mineralogical techniques. We present the first evidence for core-shell processed, natural pigment that was prepared by prehistoric people from hematitic red ochre. This involved combining the darker red outer shell with the less intensely coloured core to efficiently produce an economical, yet still strongly coloured, paint. We demonstrate the antiquity of the site as having operated between 14-13 kcal BP, during the Epigravettian period. This is based on new radiocarbon dating of bone artefacts associated with the quarry site. The dating results indicate the site to be the oldest known evidence for core-shell pigment processing. We show that the ochre mined at Lovas was exported from the site based on its characteristic signature at other archaeological sites in the region. Our discovery not only provides a methodological framework for future characterisation of ochre pigments, but also provides the earliest known evidence for "value-adding" of products for trade. PMID- 26147809 TI - Prevalence of Kaposi's sarcoma associated herpesvirus among men attending sexually transmitted infections clinics in Anhui, China. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) may be transmitted via sexual contacts, but limited information is available on KSHV infection status among sexually transmitted infection (STI) patients in China. The main objective of the present study was to determine the KSHV seroprevalence and its risk factors among male STI patients. A cross-sectional survey was conducted in three prefectures of Anhui province, China, between June and September 2013. A total of 1,600 male patients who visited an STI clinic were invited, and 1,372 participated in the study. Data were abstracted from the medical records for all the patients. Blood samples were collected and tested for antibodies to KSHV, HIV, HCV, and syphilis. Factors associated with KSHV seropositivity were examined using multivariable logistic regression analysis. The overall prevalence of KSHV, HIV, HCV, and syphilis was 13.3%, 0.7%, 0.6%, and 12.5%, respectively. After adjusting for potential confounders, KSHV infection was significantly associated with ever having anal sex with men (19 out of 30 males, OR: 8.64, 95%CI: 1.92-38.79) and HIV infection (six out of nine HIV-positive individuals, OR: 8.39, 95%CI: 1.80 39.04). There were no significant associations of KSHV infection with drug use, heterosexual sex behaviors, syphilis, and HCV. Our finding has shown that a relatively moderate prevalence of KSHV was found among male STI patients. While an increased risk for KSHV infection was observed among participants with homosexual contacts. Routine KSHV testing is recommended for male individuals attending STI clinics. PMID- 26147810 TI - Metal phytoremediation potential of naturally growing plants on fly ash dumpsite of Patratu thermal power station, Jharkhand, India. AB - Three naturally growing plants Ipomoea carnea, Lantana camara, and Solanum surattense were found in fly ash dumpsite of Patratu thermal power station, Jharkhand, India. They were assessed for their metal uptake potential. The fly ash was slightly alkaline with very less nitrogen and organic carbon but enriched with phosphorus and heavy metals. Lantana camara and Ipomoea carnea showed good translocation from root to shoot for most of the metals except Mn and Pb. The order of metal accumulation in stem of both the plants were Fe(205mg/kg)>Mn(65mg/kg)>Cu(22.35mg/kg)>Pb(6.6mg/kg)>Cr(3.05mg/kg)>Ni(1 mg/kg)>Cd(0.5 mg/kg) and Fe(741 mg/kg)>Mn(154.05 mg/kg)>Cu(20.75 mg/kg)>Pb(6.75 mg/kg)>Ni(4.0 mg/kg)>Cr(3.3mg/kg)>Cd(0.05mg/kg), respectively. But Solanum surattense accumulated most of the metals in roots. The order was in the following order, Mn (382.2mg/kg) >Fe (264.1mg/kg) > Cu (25.35mg/kg) >Pb (5.95 mg/kg) > Ni (1.9 mg/kg) > Cr (1.8mg/kg) > Cd (0.55 mg/kg). The order of Bioconcentration factor (BCF) in root and shoot followed almost the same order as, Mn>Fe>Ni>Pb>Cu>Cr~ Cd in all the three species. ANOVA showed significant variation in metal accumulation by root and stem between the species. Finally, it can be concluded that Solanum surattense can be used as phytostabilizer and other two species as phytoextractor of metal for fly ash dumpsite reclamation. PMID- 26147811 TI - A potyvirus vector efficiently targets recombinant proteins to chloroplasts, mitochondria and nuclei in plant cells when expressed at the amino terminus of the polyprotein. AB - Plant virus-based expression systems allow quick and efficient production of recombinant proteins in plant biofactories. Among them, a system derived from tobacco etch virus (TEV; genus potyvirus) permits coexpression of equimolar amounts of several recombinant proteins. This work analyzed how to target recombinant proteins to different subcellular localizations in the plant cell using this system. We constructed TEV clones in which green fluorescent protein (GFP), with a chloroplast transit peptide (cTP), a nuclear localization signal (NLS) or a mitochondrial targeting peptide (mTP) was expressed either as the most amino-terminal product or embedded in the viral polyprotein. Results showed that cTP and mTP mediated efficient translocation of GFP to the corresponding organelle only when present at the amino terminus of the viral polyprotein. In contrast, the NLS worked efficiently at both positions. Viruses expressing GFP in the amino terminus of the viral polyprotein produced milder symptoms. Untagged GFPs and cTP and NLS tagged amino-terminal GFPs accumulated to higher amounts in infected tissues. Finally, viral progeny from clones with internal GFPs maintained the extra gene better. These observations will help in the design of potyvirus-based vectors able to coexpress several proteins while targeting different subcellular localizations, as required in plant metabolic engineering. PMID- 26147812 TI - The efficacy of Italian guidelines in promoting oral health in children and adolescents. AB - AIM: The purpose of the study was to evaluate the efficacy of the guidelines on oral health published by the Italian Health Ministry. MATERIALS AND METHODS: STUDY DESIGN: 1239 patients (582 girls and 657 boys) with a mean age of 4.46 (SD 2.81) years were evaluated before application of the guidelines by paediatricians (T0) for the presence of caries, gingivitis, diseases of the oral mucosa, and malocclusion. Only patients aged 6 months, 3 years, 6 years, and 9 years at T0 were taken into consideration. All patients were reevaluated after application of the ministerial guidelines (T1). METHODS: the study took place over a 3-year period. Enrolled patients referred to the outpatient clinics of three paediatricians of the Province of Genoa who strictly applied the ministerial guidelines. STATISTICS: Chi square test analysis was performed to evaluate a statistically significant decrease in the incidence of caries, gingivitis and diseases of the oral mucosa. RESULTS: After a 3-year follow-up collected data underlined a statistically significant decrease in the incidence of dental caries, gingivitis and oral mucosal diseases after implementation of the recommended ministerial guidelines. A statistically significant decrease of malocclusions was also evident in the elder patients (12 years old at T1). CONCLUSION: The accurate implementation of the Guidelines is supported. Only collaboration and increased synergy between paedodontists and paediatricians can fulfill the objectives which were the reason for publishing the "National guidelines for the promotion of oral health and the prevention of oral diseases in developmental age". PMID- 26147813 TI - Unilateral condylar hyperplasia: diagnosis, clinical aspects and operative treatment. A case report. AB - BACKGROUND: Condylar hyperplasia of the mandible is an uncommon idiopathic disorder of the jaw characterised by increased volume of the condyle, unilaterally or bilaterally, leading to facial asymmetry, mandibular deviation, malocclusion and articular dysfunction. CASE REPORT: The authors present one case of unilateral condylar hyperplasia of a 16-year-old patient affected by severe facial asymmetry. Conventional X-rays examinations, multislice spiral CT and bone SPECT were used for the final diagnosis of primary condyle hyperplasia. The patient was treated with a combined orthodontic and surgical approach. CONCLUSION: Treatment of condylar hyperplasia with a combined orthodontic and surgical approach including condylectomy yield good aesthetic and functional outcomes. PMID- 26147814 TI - How to proceed in case of tooth avulsion: state of student knowledge. AB - AIM: Sport-related dental injuries are a growing concern worldwide. Regardless of how minor they may appear, some of them can lead to traumas which have a negative impact on quality of life, producing psychological and social discomfort. In view of the widespread lack of knowledge with regard to first aid procedures in cases of dental trauma, we would like to report the current state of knowledge of an academy of physical education and sport students compared with medical and general university students. MATERIALS AND METHODS: In order to assess the knowledge of appropriate first aid procedures following dental trauma a survey using questionnaires was undertaken. The sample size consisted of 356 students attending the last year of university: sport academy (123 students); medical university (115 students); general university (118 students). RESULTS: The results revealed that just 3% of all students knew that in the case of dental avulsion immediate replantation should be performed. Only 6% of students were aware that the time factor after tooth avulsion is the single most influential factor affecting the prognosis. Only 16% of sport academy students and 23% of general university students knew the recommended transport medium for an avulsed tooth. CONCLUSION: In the face of such poor knowledge regarding dental injuries there is an urgent need for adequate education programs on the subject of sport related orofacial injuries directed at all sports students, including athletes, players and coaches, so they could offer immediate help at the site of an accident. PMID- 26147815 TI - Prevalence and prevention of dental injuries in young taekwondo athletes in Croatia. AB - AIM: The aim of this study was to evaluate the occurrence of dental and facial injuries, the habit of wearing mouthguard and the awareness regarding injury prevention and first aid after tooth avulsion among young taekwondo athletes in Croatia. MATERIALS AND METHODS: A survey on a sample of 484 taekwondo athletes was conducted, which included 271 male (56%) and 213 female (44%) athletes aged between 8 and 28 years. The questionnaire submitted to the athletes contained 15 questions about dental trauma, use of mouthguard, dental trauma prevention, level of awareness about tooth avulsion and replantation and disturbances associated with mouthguard use. Collected data were evaluated according to gender, age groups and duration of actively engagement in taekwondo. Descriptive statistics and Chi-square tests were used for comparisons between groups. RESULTS: From the survey 300 (62%) of 484 athletes had sustained one serious injury and 103 (21%) had sustained an orofacial injury, while 194 (40%) had observed another player sustaining a dental injury. Higher number of orofacial injuries was observed in males (24%) than in females (18%). Furthermore, 98 (20%) athletes have experienced one or more dental injuries, and out of these 98 suffering dental injury 60 were male (61%) and 38 were female (39%). The frequency of orofacial injuries in the older group (42%) is higher than in three younger groups (younger cadets 25%; cadets 13%; juniors 20%) (p<0.05). Mouthguard wearing was recorded in 465 athletes (96%), 47.1% of them wear stock mouthguard, 47.6% wear boil and bite mouthguard, but only 5.3% were custom-made mouthguards. Most of them (96%) consider that mouthguards are useful for injury prevention in taekwondo. CONCLUSION: The results of this survey show that dental and orofacial injuries occur in taekwondo in all age groups but mostly in the senior group. Taekwondo players know the importance of mouthguard use, but only 5% use custom made mouthguards. This is not adequate for dental injury prevention and highlights the important role of dental professional in education of athletes for advocating the use of custom made mouthguards. PMID- 26147816 TI - Evaluation of a modified Pulpotec endodontic approach on necrotic primary molars: a one-year follow-up. AB - AIM: The aim of this study was to evaluate the effectiveness of a Pulpotec modified endodontic approach on primary molars presenting necrotic pulp and furcation bone loss in a cohort of healthy children. MATERIALS AND METHODS: Forty primary necrotic molars in healthy children, aged between 4 and 6 years underwent clinical and radiological assessment. A chemomechanical removal of pulpal necrotic debris was performed with 1% sodium hypochlorite irrigation. The canals were dried and Pulpotec was inserted in the pulp chamber, and the teeth were then restored. Clinical evaluation, vertical and horizontal measurements of the bone radiolucency were performed for up to one year after the Pulpotec procedure. STATISTICAL ANALYSIS: Wilcoxon signed-rank test was applied for comparison of groups. RESULTS: In this study 67.7% of patients showed healing of bone loss, and a significant difference in height and width of the lesion was observed (respectively 80.6%, 71%; p<0.05; p<0.025). CONCLUSION: This technique can be used as an alternative to conventional endodontic treatment for primary necrotic teeth. This procedure may allow paedodontists the ability to postpone extraction of necrotic teeth in particular situations or until eruption of the first permanent molar. Necrotic primary molars presenting furcation bone lesion due to infection may be treated with this modified Pulpotec procedure. With certain caveats, this procedure will preserve the molar on the dental arch for a certain period of time. In our study this technique yielded significant clinical improvements, but the radiological improvement is considered moderate. Future investigations are warranted in order to determine the possible effects of Pulpotec on the succedaneous teeth as well as their path of eruption. PMID- 26147817 TI - Rapid maxillary expansion in early-mixed dentition: effectiveness of increasing arch dimension with anchorage on deciduous teeth. AB - AIM: To assess the effectiveness of a Haas expander anchored to deciduous teeth in changing dental arch dimension and improving crowding and to evaluate stability of changes until permanent dentition. MATERIALS AND METHODS: STUDY DESIGN: closed cohort retrospective and case-control study. Eighteen patients undergoing early treatment for lateral crossbite (mean age 7.6 yrs; SD 1.0) at two practices located in La Spezia and Massa (Italy) were analysed. The treated group was compared with 72 control subjects divided into: 32 untreated adolescents with and without lateral crossbite and the same canine dental class as treated patients before expansion (Class II Division 2), 18 adults and 18 adolescents with dental Class I. All groups were matched for gender (ratio males:females, 8:10). The dental casts images of treated patients were digitally measured before and after treatment, and in permanent dentition. Patients at the last follow-up were compared with control subjects. RESULTS: In treated patients the increase in intermolar width and the improvement in anterior crowding were significant and stable until adolescence. Untreated adolescents with lateral crossbite showed the narrowest transversal widths and the highest irregularity. No difference was found among treated patients, adolescents without lateral crossbite, and adolescents and adults with a normal occlusion. CONCLUSIONS: The Haas expander anchored on deciduous teeth is effective in improving dental arch constriction and crowding in patients treated for lateral crossbite. The result is stable until permanent dentition. In absence of treatment, constriction of dental arch may persist, with a higher level of irregularity. PMID- 26147818 TI - Comparison of injection pain caused by the DentalVibe Injection System versus a traditional syringe for inferior alveolar nerve block anaesthesia in paediatric patients. AB - AIM: To compare paediatric patients' pain during needle insertion and injection in inferior alveoler nerve block (IANB) anaesthesia injected by either a traditional syringe (TS) or the DentalVibe Injection Comfort System (DV). MATERIALS AND METHODS: STUDY DESIGN: the study was a randomised controlled crossover clinical trial, comprised of 60 children aged 6-12 requiring an operative procedure with IANB anaesthesia on their mandibular molars bilaterally. One of the molar teeth was treated with TS and the contralateral tooth was treated with DV. On each visit, subjective and objective pain was evaluated using the Wond-Baker Faces Pain Rating Scale (PRS) and the Face, Legg, Cry, Consolability Scale (FLACC Scale). Patients were asked which anaesthesia technique they preferred. Data were analysed using Wilcoxon signed rank, Spearman correlation, and Mann-Whitney U tests. RESULTS: There were no statistically significant differences for pain evalution during needle insertion and injection of each injection system. However, a negative correlation was found on the FLACC between age and pain scores during injection after using DV. CONCLUSION: Paediatric patients experienced similar pain during IANB anaesthesia administered with TS and DV. With increased age, pain values reduced during anaesthetic agent injection with DV according to FLACC. The traditional procedure was preferred to DV in paediatric patients. PMID- 26147819 TI - Multimodal airway evaluation in growing patients after rapid maxillary expansion. AB - AIM: The objective of this study was to evaluate the airway volume of growing patients combining a morphological approach using cone beam computed tomography associated with functional data obtained by polysomnography examination after rapid maxillary expansion treatment. MATERIALS AND METHODS: STUDY DESIGN: 22 Caucasian patients (mean age 8.3+/-0.9 years) undergoing rapid maxillary expansion with Haas type expander banded on second deciduous upper molars were enrolled for this prospective study. Cone beam computed tomography scans and polysomnography exams were collected before placing the appliance (T0) and after 12 months (T1). METHODS: Image processing with airway volume computing and analyses of oxygen saturation and apnoea/hypopnoea index were performed. RESULTS: Airway volume, oxygen saturation and apnea/hypopnea index underwent significant increase over time. However, no significant correlation was seen between their increases. CONCLUSION: The rapid maxillary expansion treatment induced significant increases in the total airway volume and respiratory performance. Functional respiratory parameters should be included in studies evaluating the RME treatment effects on the respiratory performance. PMID- 26147820 TI - The effect of nasal midazolam premedication on parents-child separation and recovery time in dental procedures under general anaesthesia. AB - AIM: For many children medical and dental procedures, unfamiliar dental staff and treatment places are disturbing and stressful. Stress in children often makes them uncooperative. General anaesthesia is indicated for anxious uncooperative children or those who are disabled, immature or too young to undergo dental treatment by other means. Moreover parents' separation while entering the operative room is a traumatic experience for children. Thus premedication such as midazolam is recommended to decrease child's stress. In these situations the increased recovery time was considered as one of the midazolam side effects. There is no study that evaluated the effect of midazolam both in parents-child separation and recovery time in long dental procedure. The purpose of this study was to evaluate the effect of nasal midazolam premedication with placebo on parents-child separation and recovery times in uncooperative paediatric patients undergoing long-lasting general anaesthesia for dental procedures. MATERIALS AND METHODS: STUDY DESIGN: This randomised, double-blind study was done on 60 uncooperative patients (ASA physical status I or II) aged 2-4 years who were scheduled for general anaesthesia for dental treatment. Group A received 0.2 mg/kg intranasal midazolam as premedication, and group B received the same volume of intranasal placebo 20 minutes before entering the operating room for general anaesthesia. General anaesthesia was done with the same method for all patients, then parent-child separation and recovery times were compared between the two groups. STATISTICAL ANALYSIS: Statical significance was set at P<=0.05. Statically analysis was performed using SPSS version17.Chi-squared and student t tests were applied to analyse the data. RESULTS: We found significant differences in parents- child separation assessment between two groups. Nasal midazolam premedication had a positive effect on parents-child separation; but there was no significant difference between the two groups in terms of recovery time. CONCLUSION: Premedication of nasal midazolam before induction of general anaesthesia did not prolong recovery time but made the separation of children from their parents easier by showing a better behaviour. PMID- 26147821 TI - Mucocele of the minor salivary glands in an infant: treatment with diode laser. AB - BACKGROUND: Mucoceles are benign lesions that develop as a result of retention or extravasation of mucous material from minor salivary glands. Very uncommon in newborns and infants, they rarely may interfere with breastfeeding and compromise the respiratory function. CASE REPORT: We report a case of mucocele in a three month-old infant in the right labial commissure excised by diode laser of different wavelengths (635-980 nm), with an average power of 1.8 W, in continuous wave mode, using 300 to 320 micron optical fibers. The healing occurred in 10 days. There were no adverse effects and the patient was carefully followed-up until complete healing. CONCLUSION: T he diode laser is not only a valuable tool for mucocele eradication but it also reduces relapses, thanks to the characteristics of the laser light. PMID- 26147822 TI - Oral health in children with Down syndrome: Parents' views on dental care in Flanders (Belgium). AB - AIM: Evaluate the views and knowledge, regarding dental care, of parents who have a child with Down syndrome (DS). MATERIALS AND METHODS: Parents of children with DS were invited to fill in a questionnaire. They were recruited by the Flemish Organization for DS, from schools for children with special needs and by four multidisciplinary medical DS teams at four University Hospitals. STATISTICS: Chi square tests were used to test the correlation between different variables. Results were assessed in the 95% confidence interval with p<0.05. RESULTS: Mean age of the children was 10.1 years old (SD: 5.3). Oral health was indicated as rather good by 53% of the parents. Of the children, 66% went to a dentist within the last six months. Most of the children (64%) received a dental examination. In 53% of the cases, parents visited the same dentist for their child with DS as their other child(ren) without DS. Eighty-three percent of the parents are pleased with their dentist. They expect the dentist to be kind and reassuring. Children aged 10 years or younger get significantly more help with tooth brushing (79%) than children older than 10 years (36%). However 20% of the parents never received any oral hygiene instructions for their child with DS. CONCLUSION: Prevention is the most frequent service provided by the dentist. Parents seem to be pleased with the dentist who treats their child with DS. PMID- 26147823 TI - Ex vivo comparison of radiographic and electronic root canal length measurements in primary molars. AB - AIM: The aim of the study was to evaluate the accuracy of root canal length measurements of primary teeth using an electronic apex locator (EAL) and digital radiography in comparison to stereomicroscopic measurement as gold standard. MATERIALS AND METHODS: After preparation of access cavities of twenty extracted primary molars, the teeth were embedded in alginate blocks. Endodontic files were inserted in the root canals and the length was measured using ProPex II (Dentsply, Maillefer). When the reading was stable for 5s a silicone stop was used for reference. The true lengths of the files were then measured using a micrometer. The gold standard was determined by observing the tip of the file at the apical foramen under a stereomicroscope. For radiographic measurements standard images were obtained at 30 cm source-to-object distance, and zero degrees vertical and horizontal angulations. Radiographic images of each experimental tooth were obtained with the Digora Storage Phosphor Plates (SPP) (Soredex, Orion Corporation, Helsinki, Finland) with the x-ray unit operating at 65 kVp and 10 mA for 0.16 seconds (Trophy Radiologie, Vincennes, France). The radiographic root lengths were measured with the measurement tool of the Digora for Windows software. The mean measurements of both methods were compared to the gold standard measurements using Repeated Measure ANOVA test with Bonferroni adjustments to identify the pair-wise differences (p=0.05). RESULTS: The mean measurements obtained with the EAL (14.06+/-1.89 mm) were significantly lower than measurements done with SPP images (14.24+/-1.98 mm) (p<0.05). However, when both root canal length measurement techniques were compared to stereomicroscopic measurements (gold standard), no statistically significant difference was found. CONCLUSION: The EAL might be safer than digital radiography for the measurement of root canal length in primary teeth. PMID- 26147824 TI - Conservative approach for the management of congenital bilateral agenesis of permanent mandibular incisors: case report and literature review. AB - BACKGROUND: Agenesis of mandibular incisors can lead to compromised dental and facial aesthetics and therefore requires appropriate treatment. When retained primary incisors are associated to this condition, a medium-term restoration may be provided before any definitive treatment to provide aesthetic relief to the young patient. CASE REPORT: The aim of this paper is to discuss the aesthetic management of a case with bilateral congenital agenesis of permanent incisors and retained primary incisors, which were successfully treated with direct composite restorations. CONCLUSION: This appears a viable technique that restores function and aesthetics with a very conservative approach. PMID- 26147825 TI - Influencing factors of paediatric dental anxiety levels in an undergraduate dental clinic. AB - AIM: To examine the nature of dental anxiety in paediatric patients, and to identify factors relevant to paediatric dental anxiety in a sample of 5 to 17 year-old children residing in Cairns, Australia. MATERIALS AND METHODS: A convenient sample of 125 children, their parents and corresponding student practitioners were selected. Each was assessed with questionnaires. RESULTS: A higher level of dental anxiety was seen in children who were subject to radiographic examination as part of their treatment (b=0.462; p=0.012). Similarly, children of Asian ethnicity showed higher dental anxiety levels than their Caucasian counterparts (b=1.187; p=0.010). Finally, the childrens' overall dental anxiety levels decreased after being treated by student practitioners (t=2.311;df=124; p=0.022). CONCLUSION: Children experienced greater anxiety before receiving dental treatment than after. Treatment involving radiographic examination exacerbated dental anxiety and children of Asian descent were more anxious prior to receiving treatment. Further investigation is indicated. PMID- 26147826 TI - Dental notation for primary teeth: a review and suggestion of a novel system. AB - BACKGROUND: Tooth designation systems are routinely used in dental practice, for identification of teeth, recording dental data and communication among dental professionals. There are various dental notations systems for the primary and permanent dentition. The most popular are the Zsigmondy-Palmer system, the Universal Numbering System, and the FDI system. Others includes the Victor Haderup system, the Woelfel system, and the MICAP system. The majority of dental notations are focused on permanent teeth and are modified for primary teeth, even though the latter erupt before the permanent dentition. CONCLUSION: Advantages and disadvantages of notations for primary dentition are discussed and compared to a new alphanumeric system for primary teeth which is considered simple and convenient. PMID- 26147828 TI - Electrocatalytic Hydrogen Evolution from Molybdenum Sulfide-Polymer Composite Films on Carbon Electrodes. AB - The design of more efficient catalytic electrodes remains an important objective for the development of water splitting electrolyzers. In this context a structured composite cathode material has been synthesized by electrodeposition of molybdenum sulfide (MoSx) into a poly(pyrrole-alkylammonium) matrix, previously coated onto carbon electrodes by oxidative electropolymerization of a pyrrole-alkylammonium monomer. The composite material showed an efficient electrocatalytic activity toward proton reduction and the hydrogen evolution reaction (HER). Data from Tafel plots have demonstrated that the electron transfer rate in the composite films is fast, in agreement with the high catalytic activity of this cathode material. Bulk electrolysis of acidic water at carbon foam electrodes modified with the composite have shown that the cathodes display a high catalytic activity and a reasonable operational stability, largely exceeding that of regular amorphous MoSx electrodeposited on naked carbon foam. The enhanced catalytic performances of the composite electrode material were attributed to the structuration of the composite, which led to a homogeneous distribution of the catalyst on the carbon foam network, as shown by SEM characterizations. PMID- 26147827 TI - Recombinant pediocin in Lactococcus lactis: increased production by propeptide fusion and improved potency by co-production with PedC. AB - We describe the impact of two propeptides and PedC on the production yield and the potency of recombinant pediocins produced in Lactococcus lactis. On the one hand, the sequences encoding the propeptides SD or LEISSTCDA were inserted between the sequence encoding the signal peptide of Usp45 and the structural gene of the mature pediocin PA-1. On the other hand, the putative thiol-disulfide oxidoreductase PedC was coexpressed with pediocin. The concentration of recombinant pediocins produced in supernatants was determined by enzyme-linked immunosorbent assay. The potency of recombinant pediocins was investigated by measuring the minimal inhibitory concentration by agar well diffusion assay. The results show that propeptides SD or LEISSTCDA lead to an improved secretion of recombinant pediocins with apparently no effect on the antibacterial potency and that PedC increases the potency of recombinant pediocin. To our knowledge, this study reveals for the first time that pediocin tolerates fusions at the N terminal end. Furthermore, it reveals that only expressing the pediocin structural gene in a heterologous host is not sufficient to get an optimal potency and requires the accessory protein PedC. In addition, it can be speculated that PedC catalyses the correct formation of disulfide bonds in pediocin. PMID- 26147829 TI - Anti-proliferative effect on a colon adenocarcinoma cell line exerted by a membrane disrupting antimicrobial peptide KL15. AB - The antimicrobial and anticancer activities of an antimicrobial peptide (AMP) KL15 obtained through in silico modification on the sequences of 2 previously identified bacteriocins m2163 and m2386 from Lactobacillus casei ATCC 334 by us have been studied. While significant bactericidal effect on the pathogenic bacteria Listeria, Escherichia, Bacillus, Staphylococcus, Enterococcus is exerted by KL15, the AMP can also kill 2 human adenocarcinoma cells SW480 and Caco-2 with measured IC50 as 50 MUg/ml or 26.3 MUM. However, the IC50 determined for KL15 on killing the normal human mammary epithelial cell H184B5F5/M10 is 150 MUg/ml. The conformation of KL15 dissolved in 50% 2,2,2-trifluroroethanol or in 2 large unilamellar vesicle systems determined by circular dichroism spectroscopy appears to be helical. Further, the cell membrane permeability of treated SW480 cells by KL15 appears to be significantly enhanced as studied by both flow cytometry and confocal microscopy. As observed under a scanning electron microscope, the morphology of treated SW480 cells is also significantly changed as treating time by 80 MUg/ml KL15 is increased. KL15 appears to be able to pierce the cell membrane of treated SW480 cells so that numerous porous structures are generated and observable. Therefore, KL15 is likely to kill the treated SW480 cells through the necrotic pathway similar to some recently identified AMPs by others. PMID- 26147831 TI - Polycystic ovary syndrome (PCOS) with melanocytic mucosal macules: the role of STK11 gene polymorphisms in PCOS and Peutz-Jeghers syndrome. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex genetic disorder that is the most common endocrinopathy that affects women. OBSERVATIONS: We report two individuals with PCOS with a genetic polymorphism in serine threonine kinase 11 (STK11). Both these individuals developed mucosal pigmentation suggesting Peutz Jeghers syndrome (PJS), which is associated with mutations in STK11. Both individuals showed some improvement in their metabolic and endocrine dysregulation with therapies commonly used for PCOS. However, they continued to show progression of mucosa pigmentation. CONCLUSIONS: This is the first report of clinical overlap in individuals with PCOS and PJS, even though some individuals with PCOS show a polymorphism in STK11, which is the gene mutated in PJS. The importance of this clinical association is not clear but may be significant because of the association of STK11 dysregulation and the development of internal tumors. PMID- 26147830 TI - MUC1-Targeted Cancer Cell Photothermal Ablation Using Bioinspired Gold Nanorods. AB - Recent studies have highlighted the overexpression of mucin 1 (MUC1) in various epithelial carcinomas and its role in tumorigenesis. These mucins present a novel targeting opportunity for nanoparticle-mediated photothermal cancer treatments due to their unique antenna-like extracellular extension. In this study, MUC1 antibodies and albumin were immobilized onto the surface of gold nanorods using a "primer" of polydopamine (PD), a molecular mimic of catechol- and amine-rich mussel adhesive proteins. PD forms an adhesive platform for the deposition of albumin and MUC1 antibodies, achieving a surface that is stable, bioinert and biofunctional. Two-photon luminescence confocal and darkfield scattering imaging revealed targeting of MUC1-BSA-PD-NRs to MUC1+ MCF-7 breast cancer and SCC-15 squamous cell carcinoma cells lines. Treated cells were exposed to a laser encompassing the near-infrared AuNR longitudinal surface plasmon and assessed for photothermal ablation. MUC1-BSA-PD-NRs substantially decreased cell viability in photoirradiated MCF-7 cell lines vs. MUC1- MDA-MB-231 breast cancer cells (p < 0.005). Agents exhibited no cytotoxicity in the absence of photothermal treatment. The facile nature of the coating method, combined with targeting and photoablation efficacy, are attractive features of these candidate cancer nanotherapeutics. PMID- 26147834 TI - Diffuse Epibulbar Complex Lacrimal-Cartilaginous Choristoma: Diagnostic Clues and Management. AB - PURPOSE: To describe the clinical and histopathologic features distinguishing an extensive complex choristoma of the epibulbar surface and to address the management of such lesions. METHODS: Clinical history, diagnostic imaging studies, and histopathologic sections stained with hematoxylin and eosin were reviewed from a 2-year-old girl with a congenital conjunctival lesion of the right eye that was surgically excised. RESULTS: The patient clinically displayed an extensive, vascularized amelanotic conjunctival lesion located superotemporally with extension onto the cornea. Her visual acuity was reduced to 20/670. The clinical diagnosis was a large lacrimal gland choristoma with corneal involvement and resulting deprivation amblyopia. The patient underwent an excision of the lesion including the corneal portion, and the ocular surface was reconstructed with amniotic membrane. Histopathologic evaluation disclosed lobules of lacrimal tissue and cartilage plaques, smooth muscle, and nerves consistent with a complex choristoma. Six weeks postoperatively, the visual acuity had improved to 20/180. The patient returned to her local ophthalmologist for amblyopia management. CONCLUSIONS: We emphasize the importance of recognizing lesion-induced amblyopia and the timely performance of appropriate surgery for complex epibulbar choristomas. A differential diagnosis of other congenital epibulbar lesions is provided. PMID- 26147832 TI - Measurement of latent cognitive abilities involved in concept identification learning. AB - INTRODUCTION: We used cognitive and psychometric modeling techniques to evaluate the construct validity and measurement precision of latent cognitive abilities measured by a test of concept identification learning: the Penn Conditional Exclusion Test (PCET). METHOD: Item response theory parameters were embedded within classic associative- and hypothesis-based Markov learning models and were fitted to 35,553 Army soldiers' PCET data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). RESULTS: Data were consistent with a hypothesis-testing model with multiple latent abilities-abstraction and set shifting. Latent abstraction ability was positively correlated with number of concepts learned, and latent set-shifting ability was negatively correlated with number of perseverative errors, supporting the construct validity of the two parameters. Abstraction was most precisely assessed for participants with abilities ranging from 1.5 standard deviations below the mean to the mean itself. Measurement of set shifting was acceptably precise only for participants making a high number of perseverative errors. CONCLUSIONS: The PCET precisely measures latent abstraction ability in the Army STARRS sample, especially within the range of mildly impaired to average ability. This precision pattern is ideal for a test developed to measure cognitive impairment as opposed to cognitive strength. The PCET also measures latent set-shifting ability, but reliable assessment is limited to the impaired range of ability, reflecting that perseverative errors are rare among cognitively healthy adults. Integrating cognitive and psychometric models can provide information about construct validity and measurement precision within a single analytical framework. PMID- 26147833 TI - Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort. AB - OBJECTIVE: Combined pituitary hormonal deficiency (CPHD) can result from mutations within genes that encode transcription factors. This study evaluated the frequency of mutations in these genes in a cohort of 144 unrelated Italian patients with CPHD and estimated the overall prevalence of mutations across different populations using a systematic literature review. MATERIAL AND METHODS: A multicentre study of adult and paediatric patients with CPHD was performed. The PROP1, POU1F1, HESX1, LHX3 and LHX4 genes were analysed for the presence of mutations using direct sequencing. We systematically searched PubMed with no date restrictions for studies that reported genetic screening of CPHD cohorts. We only considered genetic screenings with at least 10 individuals. Data extraction was conducted in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Global mutation frequency in Italian patients with CPHD was 2.9% (4/136) in sporadic cases and 12.5% (1/8) in familial cases. The worldwide mutation frequency for the five genes calculated from 21 studies was 12.4%, which ranged from 11.2% in sporadic to 63% in familial cases. PROP1 was the most frequently mutated gene in sporadic (6.7%) and familial cases (48.5%). CONCLUSION: The frequency of defects in genes encoding pituitary transcription factors is quite low in Italian patients with CPHD and other western European countries, especially in sporadic patients. The decision of which genes should be tested and in which order should be guided by hormonal and imaging phenotype, the presence of extrapituitary abnormalities and the frequency of mutation for each gene in the patient-referring population. PMID- 26147835 TI - Comparative Evaluation of Silicone Hydrogel Contact Lenses and Autologous Serum for Management of Sjogren Syndrome-Associated Dry Eye. AB - PURPOSE: To comparatively evaluate the efficacy of a bandage contact lens (BCL) and autologous serum (AS) eye drops in the management of severe dry eye caused by Sjogren syndrome (SS). METHODS: In this prospective randomized study, 40 patients with SS were enrolled. Patients were divided into 2 treatment groups: BCL and AS. RESULTS: A total of 37 patients were included, 18 patients (35 eyes) in the AS group and 19 patients (36 eyes) in the BCL group. At the end of 6 weeks, the best corrected visual acuity improved significantly in the BCL group (0.5 +/- 0.3 vs. 0.3 +/- 0.2, P = 0.003) but not in the AS group (0.4 +/- 0.3 vs. 0.3 +/- 0.3, P = 0.11). The best-corrected visual acuity remained stable up to 6 weeks after discontinuation of the BCL (0.5 +/- 0.3 vs. 0.4 +/- 0.2, P = 0.03). Although the Ocular Surface Disease Index scores decreased significantly after treatment in both groups, patients in the BCL group had lower Ocular Surface Disease Index scores than those in the AS group (53.4 vs. 41.8 at week 3, 47.1 vs. 31.0 at week 6, 52.7 vs. 32.0 at week 12; P = 0.014, <0.001, <0.004, respectively). The "faces" scores showed improved quality of life in both groups. Tear break-up time improved significantly in both groups except at 6 weeks after discontinuation of the AS. Patients in the BCL group had lower corneal staining scores than those of the AS group after 6 weeks of treatment and 6 weeks after discontinuation of treatment (P < 0.01). There was no significant change in Schirmer I test scores between or within groups. CONCLUSIONS: Balafilcon A silicone hydrogel contact lenses as a BCL were effective in the management of SS-associated dry eye. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02147509. PMID- 26147836 TI - Comparison of ACIOL Retention With IOL Exchange in Patients Undergoing Descemet Stripping Automated Endothelial Keratoplasty. AB - PURPOSE: To investigate clinical outcomes in the management of anterior chamber intraocular lenses (ACIOLs) in patients requiring Descemet stripping automated endothelial keratoplasty (DSAEK) for pseudophakic corneal edema. METHODS: This is a retrospective review of DSAEK procedures performed at a single center between May 1, 2006, and August 1, 2014. RESULTS: Forty-three eyes (41 patients) with pseudophakic corneal edema and an ACIOL were identified. In 26 eyes (60.5%), the ACIOL was retained [intraocular lens retention (IOLR) group], and in 17 eyes (39.5%), intraocular lens exchange [(IOLX) group] was concurrent with DSAEK. No significant difference was noted between the IOLR and IOLX groups for the following: the incidence of primary graft failure (7.7% vs. 5.9%; P = 1.0); the incidence (3.8% vs. 0.0%; P = 1.0) or rate (0.036 per eye-year vs. 0 per eye year; P = 0.28) of secondary graft failure; or the incidence (7.7% vs. 11.8%; P = 1.0) or rate (0.056 per eye-year vs. 0.073 per eye-year; P = 0.69) of endothelial rejection. However, the incidence (23.1% vs. 58.8%; P = 0.026) and rate (0.291 per eye-year vs. 0.475 per eye-year; P = 0.033) of increased intraocular pressure were significantly higher in the IOLX group. There were more complications in the IOLX group, although the difference was not significant (7.7% vs. 29.4%; P = 0.093). CONCLUSIONS: There is no significant difference in the incidence of primary graft failure or in the rate of secondary graft failure or endothelial rejection in eyes with ACIOL retention or exchange. However, as IOLX is associated with intraoperative and postoperative complications and an increased rate of postoperative intraocular pressure elevation, we recommend performing DSAEK with retention of well-positioned ACIOLs in these eyes. PMID- 26147837 TI - Determination of Surgical Strategies for Burn-Induced Conjunctivalized Corneas Using Optical Coherence Tomography. AB - PURPOSE: To evaluate the clinical use of optical coherence tomography (OCT) in optimizing surgical treatment strategies for conjunctivalized corneas secondary to ocular burns. METHODS: This noncomparative observational study included 25 patients with stable ocular burns and conjunctivalized corneas. OCT was performed on each eye. The thickness of corneal opacity or pseudopterygium and the underlying healthy stroma were measured. Individual surgical strategies were performed based on clinical examination and OCT images. RESULTS: Three types of conjunctivalized corneas were evaluated, including conjunctival pannus (4 of 25), pseudopterygium (10 of 25), and a white fibrovascular membrane (11 of 25). All 25 patients received a procedure of allograft limbal stem cell transplantation. In addition, with information provided in OCT images, 8 patients had combined lamellar keratoplasties; 3 patients had deep anterior lamellar keratoplasties, and 2 patients received penetrating keratoplasties. The remaining 12 patients received limbal stem cell transplantation alone. All fibrovascular tissues were successfully removed from the cornea in all patients. CONCLUSIONS: OCT is a valuable method in the evaluation of conjunctivalized corneas. This is helpful in determining the surgical treatments for individual patients, allowing for less corneal graft rejection and making good use of corneal donors. PMID- 26147838 TI - Conservative Surgical Management of a Grade III Corneal Dermoid. AB - PURPOSE: To present a rare, unique, grade III corneal dermoid treated with conservative surgical management. METHODS: An 8-month-old boy was admitted to our clinic with a lesion on the central cornea of the right eye and a corneal mass in the left eye. The mass had a skin-like surface and protruded to the outside of the palpebral fissure. MRI (magnetic resonance imaging) of the orbits showed a large cyst covering most of the cornea and the absence of the anterior chamber and lens. The dermoid was excised and sent for histopathological examination. The cornea was reconstructed using the partial thickness scleral graft. RESULTS: The histopathology report confirmed the diagnosis of a grade III corneal dermoid. On examination 1 year after the surgery, the orbital and globe volumes were the same, and the intraocular pressure was normal. CONCLUSIONS: This is likely the first report of an unusual case in which a grade III corneal dermoid with an anterior staphyloma was treated by anterior segment reconstruction using an autologous partial thickness scleral graft. We believe that this technique has the advantage that it stimulates orbital and facial development and has good cosmetic results. PMID- 26147839 TI - Stamping an S on DMEK Donor Tissue to Prevent Upside-Down Grafts: Laboratory Validation and Detailed Preparation Technique Description. AB - PURPOSE: To report endothelial cell loss (ECL) caused by a novel S-stamp preparation technique for Descemet membrane endothelial keratoplasty (DMEK). METHODS: Six cadaveric human corneas were prepared for DMEK transplantation using a single standardized technique, including the application of a dry ink gentian violet S-stamp to the stromal side of Descemet membrane. Endothelial cell death was evaluated and quantified using computerized analysis of vital dye staining. RESULTS: ECL caused by the S-stamp was 0.6% (range 0.1%-1.0%), which comprised less than one-tenth of the total ECL caused by our preparation of the DMEK graft from the start to finish, including recovery, prestripping, S-stamping, and trephination (13.7% total ECL, range 9.9%-17.6%). CONCLUSIONS: Our novel S-stamp donor tissue preparation technique is intuitive to learn and holds the promise of preventing iatrogenic primary graft failure due to upside-down grafts without causing unacceptable increases in ECL. PMID- 26147840 TI - Spectral Domain OCT-Based Evaluation of the Sclera and Its Adjacent Layers. PMID- 26147841 TI - Ventricular Assist Device in Single-Ventricle Heart Disease and a Superior Cavopulmonary Anastomosis. AB - Our objective is to describe the use of a ventricular assist device (VAD) in single-ventricle patients with circulatory failure following superior cavopulmonary anastomosis (SCPA). We performed a retrospective chart review of all single-ventricle patients supported with a VAD following SCPA. Implantation techniques, physiologic parameters while supported, medical and surgical interventions postimplant, and outcomes were reviewed. Four patients were supported with an EXCOR Pediatric (Berlin Heart Inc., The Woodlands, TX, USA) following SCPA for a median duration of 10.5 days (range 9-312 days). Selective excision of trabeculae and chords facilitated apical cannulation in all patients without inflow obstruction. There were two pump exchanges in the one patient supported for 312 days. Two patients were evaluated by cardiac catheterization while supported. Three of four patients were successfully bridged to transplantation. One patient died while supported. All patients had significant bleeding at the time of transplantation, and one required posttransplant extracorporeal membrane oxygenation with subsequent full recovery. VAD support can provide a successful bridge to transplantation in patients with single ventricle circulation following SCPA. A thorough understanding of the challenges encountered during this support is necessary for successful outcomes. PMID- 26147842 TI - Effectiveness of Tai Chi on Physical and Psychological Health of College Students: Results of a Randomized Controlled Trial. AB - OBJECTIVE: To investigate the effectiveness and safety of Tai Chi Chuan (TCC) on physical and psychological health of college students. METHODS: Two hundred six college students were recruited and randomly allocated to a control group or a TCC exercise group in an equal ratio. Participants in the control group were instructed to maintain their original activity level and those in the TCC exercise group received 12 weeks of TCC exercise training based on their original activity level. Physical and psychological outcomes were evaluated at baseline, 13 weeks and 25 weeks. Intention-to-treat analysis was performed for the above outcomes. RESULTS: Compared with the control group, the TCC exercise group showed significant improvements at the end of the 12-week intervention period for flexibility (length of Sit and Reach (cm): TCC group 14.09+/-7.40 versus control 12.88+/-6.57, P = 0.039 adjusted for its baseline measures using a general linear model) and balance ability (open eyes perimeter: TCC group 235.6(191~314) versus control 261(216~300); closed eyes perimeter: TCC group 370.5 (284~454) versus control 367 (293~483); P = 0.0414, 0.008, respectively, adjusted for corresponding baseline measures using a general linear model). No significant changes in other physical and mental outcomes were found between the two groups. No adverse events were reported during the study period. CONCLUSION: TCC exercise was beneficial in college students for improving flexibility and balance capability to some extent, compared with usual exercise. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-13003328. PMID- 26147843 TI - Volume of interest-based fourier transform method for calculation of static magnetic field maps from susceptibility distributions. AB - PURPOSE: Calculation of static magnetic field (B0 ) inhomogeneity maps of high resolution susceptibility models by means of convolution with dipole kernels often encounters limitations in computer memory (RAM) for large input data matrices. In many applications, only a small portion of the full volume of the computer model is a volume of interest (VOI) or a susceptibility perturbation source. This work presents a VOI-based method to significantly reduce the computer memory usage for such applications. THEORY AND METHODS: The VOI-based method is presented and compared with the conventional method for calculation of the B0 field in the brain and heart of a human body model in terms of calculation speed, memory requirement, and calculation error relative to the full model results. RESULTS: Use of the VOI-based method significantly reduced memory usage in the human body model calculations over the conventional method without loss of accuracy and with comparable calculation speed. CONCLUSION: The proposed method can be valuable for rapid calculation of B0 distributions on standard computer hardware for applications such as subject-specific B0 field calculations derived from anatomic scans. Magn Reson Med 75:2473-2480, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26147844 TI - Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface. AB - Static strain in complex oxide heterostructures has been extensively used to engineer electronic and magnetic properties at equilibrium. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion. Light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism, for example by driving domain wall motion to transport information across suitably designed devices. PMID- 26147845 TI - Dislocation locking versus easy glide in titanium and zirconium. AB - The ease of a metal to deform plastically in selected crystallographic planes depends on the core structure of its dislocations. As the latter is controlled by electronic interactions, metals with the same valence electron configuration usually exhibit a similar plastic behaviour. For this reason, titanium and zirconium, two transition metals of technological importance from the same column of the periodic table, have so far been assumed to deform in a similar fashion. However, we show here, using in situ transmission electron microscopy straining experiments, that plasticity proceeds very differently in these two metals, being intermittent in Ti and continuous in Zr. This observation is rationalized using first-principles calculations, which reveal that, in both metals, dislocations may adopt the same set of different cores that are either glissile or sessile. An inversion of stability of these cores between Zr and Ti is shown to be at the origin of the profoundly different plastic behaviours. PMID- 26147846 TI - Brownian diffusion of a partially wetted colloid. AB - The dynamics of colloidal particles at interfaces between two fluids plays a central role in microrheology, encapsulation, emulsification, biofilm formation, water remediation and the interface-driven assembly of materials. Common intuition corroborated by hydrodynamic theories suggests that such dynamics is governed by a viscous force lower than that observed in the more viscous fluid. Here, we show experimentally that a particle straddling an air/water interface feels a large viscous drag that is unexpectedly larger than that measured in the bulk. We suggest that such a result arises from thermally activated fluctuations of the interface at the solid/air/liquid triple line and their coupling to the particle drag through the fluctuation-dissipation theorem. Our findings should inform approaches for improved control of the kinetically driven assembly of anisotropic particles with a large triple-line-length/particle-size ratio, and help to understand the formation and structure of such arrested materials. PMID- 26147847 TI - Metallurgy: Starting and stopping dislocations. PMID- 26147848 TI - Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis. AB - Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2 cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma. PMID- 26147849 TI - Changes in Estrogen Receptor ERbeta (ESR2) Expression without Changes in the Estradiol Levels in the Prostate of Aging Rats. AB - Although the prostate is androgen-dependent, it is also influenced by estrogens, which act via the estrogen receptors ERalpha and ERbeta. In the prostate, ERbeta is highly expressed in the epithelium and appears to participate in the regulation of cell proliferation, apoptosis and differentiation. Evidence shows that ERbeta is decreased in malignant prostate, suggesting that it plays an important role in protecting this tissue. Despite the relationship between reductions in ERbeta and abnormal growth of the gland, little is known about the age-dependent variation of this receptor. Therefore, we aimed to investigate ERbeta expression in the prostatic lobes of aging Wistar rats (3 to 24 months). Histopathological alterations, including hyperplasia, intraluminal concretions, nuclear atypia and prostate intraepithelial neoplasias (PIN), were observed in the prostates of aging rats. Epithelial proliferation led to cribriform architecture in some acini, especially in the ventral prostate (VP). In the VP, areas of epithelial atrophy were also observed. Furthermore, in the lateral prostate, there was frequent prostatitis. Immunohistochemistry revealed that the expression of ERbeta is reduced in specific areas related to PIN, atrophic abnormalities and cellular atypia in the prostate epithelium of senile rats. Corroborating the involvement of the receptor with proliferative activity, the punctual reduction in ERbeta paralleled the increase in cell proliferation especially in areas of PIN and nuclear atypies. The decrease in ERbeta reactivity occurred in a hormonal milieu characterized by a constant concentration of estradiol and decreased plasmatic and tissue DHT. This paper is a pioneering study that reveals focal ERbeta reduction in the prostate of aging rats and indicates a potential disorder in the ERbeta pathway. These data corroborate previous data from humans and dogs that silencing of this receptor may be associated with premalignant or malignant conditions in the prostate. PMID- 26147850 TI - Social media and pharmacovigilance: A review of the opportunities and challenges. AB - Adverse drug reactions come at a considerable cost on society. Social media are a potentially invaluable reservoir of information for pharmacovigilance, yet their true value remains to be fully understood. In order to realize the benefits social media holds, a number of technical, regulatory and ethical challenges remain to be addressed. We outline these key challenges identifying relevant current research and present possible solutions. PMID- 26147852 TI - Submerged flapless technique vs. conventional flap approach for implant placement: experimental domestic pig study with 12-month follow-up. AB - OBJECTIVES: The aim of our study was to compare osseointegration and peri-implant crestal bone resorption in submerged flapless and conventional flap surgery over a 12-month follow-up. MATERIALS AND METHODS: The study used five domestic pigs. Implants were inserted 9 weeks after tooth extraction. Each animal received six implants in the mandible, following a split-mouth design: one side was treated using a flapless technique using mini-incisions, while a flap was raised on the other. The animals were sacrificed at 2 weeks, 1, 3, 6 and 12 months after implant placement. Radiographic images were taken to analyze crestal bone loss, and samples were extracted for histopathological and bone-to-implant contact (BIC) analyses. RESULTS: Significantly, greater crestal bone loss (P = 0.005) was obtained in the flap group compared with the flapless group. The flapless group presented significantly higher percentages of BIC (P < 0.05) at 3, 6 and 12 months compared with the conventional flap group. CONCLUSIONS: Within the limitations of this experimental animal study, it may be concluded that the type of surgery (flap or flapless) affects peri-implant bone preservation and osseointegration of regular platform implants. Flapless surgery is associated with peri-implant crestal bone preservation. Flapless surgery in combination with submerged implants allows higher osseointegration values. PMID- 26147851 TI - Identities of P2 and P3 Residues of H-2Kb-Bound Peptides Determine Mouse Ly49C Recognition. AB - Ly49 receptors can be peptide selective in their recognition of MHC-I-peptide complexes, affording them a level of discrimination beyond detecting the presence or absence of specific MHC-I allele products. Despite this ability, little is understood regarding the properties that enable some peptides, when bound to MHC I molecules, to support Ly49 recognition, but not others. Using RMA-S target cells expressing MHC-I molecules loaded with individual peptides and effector cells expressing the ectodomain of the inhibitory Ly49C receptor, we found that two adjacent amino acid residues, P2 and P3, both buried in the peptide binding groove of H-2Kb, determine mouse Ly49C specificity. If both are aliphatic residues, this is supportive. Whereas, small amino acids at P2 and aromatic amino acids at the P3 auxiliary anchor residue are detrimental to Ly49C recognition. These results resemble those with a rat Ly49 where the identity of a peptide anchor residue determines recognition, suggesting that dependence on specific peptide residues buried in the MHC-I peptide-binding groove may be fundamental to Ly49 peptide selectivity and recognition. PMID- 26147853 TI - The Cold Shock Domain of YB-1 Segregates RNA from DNA by Non-Bonded Interactions. AB - The human YB-1 protein plays multiple cellular roles, of which many are dictated by its binding to RNA and DNA through its Cold Shock Domain (CSD). Using molecular dynamics simulation approaches validated by experimental assays, the YB1 CSD was found to interact with nucleic acids in a sequence-dependent manner and with a higher affinity for RNA than DNA. The binding properties of the YB1 CSD were close to those observed for the related bacterial Cold Shock Proteins (CSP), albeit some differences in sequence specificity. The results provide insights in the molecular mechanisms whereby YB-1 interacts with nucleic acids. PMID- 26147854 TI - Effect of Novel Starter Culture on Reduction of Biogenic Amines, Quality Improvement, and Sensory Properties of Doenjang, a Traditional Korean Soybean Fermented Sauce Variety. AB - To select appropriate microorganisms as starter cultures for the reliable and reproducible fermentation of soybean fermented products of Korean Doenjang, various ratios of fungi (Aspergillus oryzae J, Mucor racemosus 15, M. racemosus 42) combined with Bacillus subtilis TKSP 24 were selected as either single, double, or multiple Meju strains for commercial mass production of Doenjang, followed by analysis of sensory characteristics. In the sensory evaluation, Doenjang BAM15-1 and BAM42-1, which were fermented with multiple strains (1:1:1), showed the highest sensory scores as compared to control. Based on sensory characteristics, 6 Doenjang samples were subjected to quantitative determination of amino acids, free sugars, and organic acids (volatile and nonvolatile) contents, followed by determination of biogenic amines. Total sweet taste amino acid contents were highest in BAM15-1 and BAM42-1 samples (333.7 and 295.8 mg/100 g, respectively) and similar that of control (391.1 mg/100 g). Samples BAM15-1 and BAM42-1 showed the relatively high volatile and nonvolatile organic acid contents (154.24, 192.26, and 71.31, 82.42 mg/100 g, respectively). In addition, BAM15-1 and BAM42-1 showed negligible biogenic amine formation, ranging from 0.00 to 1.02 and 0.00 to 3.92 mg/100 g, respectively. These findings indicate that determination of food components along with sensory and quality attributes using multiple microbial Meju strains as a starter culture may provide substantial results on improved quality fermented Doenjang products. PMID- 26147855 TI - The Impact of Illicit Use of Amphetamine on Male Sexual Functions. AB - INTRODUCTION: Data concerning the impact of amphetamine on male sexual functions are limited, although amphetamine has been used as an aphrodisiac. AIMS: This cross-sectional study was to assess the impact of illicit use of amphetamine on male sexual functions. METHODS: Male illicit drug users in a Drug Abstention and Treatment Center were recruited to complete a self-administered questionnaire, and data were compared with age-matched controls. MAIN OUTCOME MEASURES: The International Index of Erectile Function (IIEF) and global assessment questions were used to assess sexual functions. RESULTS: Of 1,159 amphetamine mono-illicit drug users, the mean age was 31.9 +/- 7.5 (18-57) years, and mean duration of drug use was 30.7 +/- 52.2 (median 9, range 0.1-252) months. Half of them reported that drug use had no impact on their sexual functions. The other half reported drug impacts as reduced erectile rigidity and sexual life satisfaction, enhanced orgasmic intensity, and prolonged ejaculation latency time more often than the opposite effects, while they reported enhanced or reduced effect equally on sexual desire. Dosing frequency of amphetamine was associated with its impact on sexual functions, but duration of its use had little association with that. Compared with 211 age-matched controls, the amphetamine mono-illicit drug users had lower IIEF scores in the domains of erectile function, orgasmic function, and overall satisfaction, but there are no significant differences in intercourse satisfaction and sexual desire scores. The prevalence of erectile dysfunction (ED) was significantly higher in the drug users than in the controls (29.3% vs. 11.9%). The odds ratio of ED for amphetamine use was 2.1 (95% confidence interval 1.2-3.6) after adjustment for other risk factors. CONCLUSIONS: The impact of illicit use of amphetamine on male sexual functions varied among users, and their ED prevalence was higher than the controls. PMID- 26147857 TI - Learning to See Beneath the Surface: A Qualitative Analysis of Family Medicine Residents' Reflections About Communication. AB - Patients share straightforward statements with physicians such as describing their fears about their diagnosis. Physicians need to also understanding implicit, indirect, subtle communication cues that give broader context to patients' illness experiences. This project examines physicians' written reflections that offer insight into their interpretation of both the stated and the tacit aspects of their observations about communication, their resulting responses, and their intended actions. Tufts University Family Medicine residents (N = 33) of the Tufts Family Medicine Cambridge Health Alliance completed three reflective exercises each week over the course of 1 year (756 reflective entries). An interdisciplinary research team identified communication-related concepts within the reflections. Identified themes include (a) physicians recognizing and discovering mutual interplay of their communication with and patient disclosure, (b) physicians paying attention to subtleties of patient behavior as indicative of a fuller picture of patients' lives and their coping with illness, and (c) physician images of growth and awareness about communication indicative of their potential for growth and improvement. The project extends the literature in communication and medical education by examining explicit and tacit points of reflection about communication. The project (a) allows for unpacking the multifaceted aspects of reflection and (b) bridges reflective theory and medical education with communication foundations. PMID- 26147856 TI - Rhizoma Paridis Saponins Suppresses Tumor Growth in a Rat Model of N Nitrosomethylbenzylamine-Induced Esophageal Cancer by Inhibiting Cyclooxygenases 2 Pathway. AB - Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N nitrosomethylbenzylamine (NMBA, 1 mg/kg) for 10 weeks. RPS (350 mg/kg or 100 mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer. PMID- 26147858 TI - Exploring the consistency, transparency and portability of dental technology education: benchmarking across Norway, Ireland and Australia. AB - Dental technology programmes of study must prepare students to practice in a broad range of contemporary workplaces. Currently, there is limited evidence to benchmark dental technology education - locally, nationally or internationally. This research aims to improve consistency, transparency and portability of dental technology qualifications across three countries. Data were accessed from open source curriculum documents and five calibrated assessment items. Three institutions collaborated with Oslo and Akershus University College, Norway; Trinity College Dublin, Ireland; and Griffith University, Australia. From these, 29-44 students completed 174 assessments. The curricula reflect the community needs of each country and display common themes that underpin professional dental technology practice. Assessment results differed between institutions but no more than a normal distribution. Face-to-face assessment moderation was critical to achieve consistency. This collaborative research has led to the development of a set of guidelines for other dental technology education providers interested in developing or aligning courses internationally to enhance the portability of qualifications. PMID- 26147859 TI - Diagnosis of Hepatic Angiomyolipoma by Combination of Baseline and Contrast Enhanced Ultrasound--A Prospective Study in Non-Cirrhotic Patients. AB - OBJECTIVES: Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal tumor of the liver and its diagnosis has been considered challenging. The aim of this study was to investigate prospectively the diagnostic efficacy of the incorporation of both baseline ultrasound (US) and contrast-enhanced ultrasound (CEUS) features of HAML in patients without cirrhosis. MATERIALS AND METHODS: Consecutive 1748 non-cirrhotic patients with focal liver lesions (FLLs) were prospectively enrolled. Baseline US and CEUS were performed before resection or biopsy. Ultrasound imaging diagnosis of FLLs was compared with the pathological results. RESULTS: Final diagnoses were established in 41 patients with HAML (2.3%) with normal alpha fetal protein (AFP) level and in 1707 patients with FLL other than HAML. Diagnostic criteria for HAML was based on the combination of baseline US and CEUS appearance of the nodule: (1) Well-defined, marked hyper echoic nodule without surrounding hypo-echoic halo on baseline US; (2) hyper enhancement in the arterial phase (exclude initial peripheral nodular enhancement and spoke-wheel arteries) and remains hyper-enhancement or iso-enhancement in the late phase. The diagnostic criteria were fulfilled in 31 HAMLs, 1 hepatocellular adenoma and 1 hemangioma. Ten HAMLs were misdiagnosed as other liver tumors because they did not meet the diagnostic criteria mentioned above and consequently yielded a sensitivity, specificity, positive predictive values, negative predictive values and Youden index of 75.61%, 99.88%, 93.94%, 99.42%, and 0.75 respectively. CONCLUSION: The combination of baseline US and CEUS may lead to the correct diagnosis noninvasively in the majority of HAMLs in non cirrhotic patients with normal AFP level. PMID- 26147860 TI - Development of a Novel Tetravalent Synthetic Peptide That Binds to Phosphatidic Acid. AB - We employed a multivalent peptide-library screening technique to identify a peptide motif that binds to phosphatidic acid (PA), but not to other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). A tetravalent peptide with the sequence motif of MARWHRHHH, designated as PAB-TP (phosphatidic acid-binding tetravalent peptide), was shown to bind as low as 1 mol% of PA in the bilayer membrane composed of PC and cholesterol. Kinetic analysis of the interaction between PAB-TP and the membranes containing 10 mol% of PA showed that PAB-TP associated with PA with a low dissociation constant of KD = 38 +/- 5 nM. Coexistence of cholesterol or PE with PA in the membrane enhanced the PAB-TP binding to PA by increasing the ionization of the phosphomonoester head group as well as by changing the microenvironment of PA molecules in the membrane. Amino acid replacement analysis demonstrated that the tryptophan residue at position 4 of PAB-TP was involved in the interaction with PA. Furthermore, a series of amino acid substitutions at positions 5 to 9 of PAB-TP revealed the involvement of consecutive histidine and arginine residues in recognition of the phosphomonoester head group of PA. Our results demonstrate that the recognition of PA by PAB-TP is achieved by a combination of hydrophobic, electrostatic and hydrogen-bond interactions, and that the tetravalent structure of PAB-TP contributes to the high affinity binding to PA in the membrane. The novel PA-binding tetravalent peptide PAB-TP will provide insight into the molecular mechanism underlying the recognition of PA by PA-binding proteins that are involved in various cellular events. PMID- 26147861 TI - State rumination enhances elaborative processing of negative material as evidenced by the late positive potential. AB - Rumination has been shown to increase negative affect and is highly associated with increased duration of depressive episodes. Previous research has shown that enhanced elaborative processing of negative stimuli is often associated with depression and trait rumination. We hypothesized that engaging in rumination would result in sustained elaborative processing of negative information, as measured by late positive potential (LPP) asymmetry, regardless of depression. Participants were experimentally induced to engage in ruminative- or distraction oriented thoughts and subsequently viewed negative, positive, and neutral images. Our results showed a very specific right-dominant frontal and parietal LPP to negative, but not neutral or positive, pictures in the rumination condition only that was not correlated with any measures of trait rumination or depression symptoms. This suggests that state rumination alone may lead to an enhanced, sustained processing of negative material that is typically associated with depression. (PsycINFO Database Record PMID- 26147862 TI - The effect of emotional state on visual detection: A signal detection analysis. AB - This research explores the effect of emotional states on visual detection. Previous research has shown that emotional states characterized by an intolerance of uncertainty, such as anxiety, can affect performance on visual detection tasks. It is unclear, however, to what extent these effects are a result of increased perceptual ability, a decisional bias, or both. The present study used signal detection theory to determine whether uncertain emotional states affect perceptual discriminability and/or decisional bias. In 2 experiments, an anxious, angry, or calm emotional state was induced, and participants were asked to identify which of a series of noisy images contained an embedded target image. The target images were either faces or houses. Emotional state had no effect on decisional bias for either target, but the ability to detect a face was higher for anxious participants. No effect on discriminability was found for houses. These results suggest that emotional state can change perceptual discriminability, but that this change may be limited to certain stimulus classes. PMID- 26147863 TI - Mental health service use for adult patients with co-occurring depression and physical chronic health care needs, 2007-2010. AB - BACKGROUND: Individuals with mental illness experience poor health and may die prematurely from chronic illness. Understanding whether the presence of co occurring chronic physical health conditions complicates mental health treatment is important, particularly among patients seeking treatment in primary care settings. OBJECTIVES: Examine (1) whether the presence of chronic physical conditions is associated with mental health service use for individuals with depression who visit a primary care physician, and (2) whether race modifies this relationship. RESEARCH DESIGN: Secondary analysis of the National Ambulatory Medical Care Survey, a survey of patient-visits collected annually from a random sample of 3000 physicians in office-based settings. SUBJECTS: Office visits from 2007 to 2010 were pooled for adults aged 35-85 with a depression diagnosis at the time of visit (N=3659 visits). MEASURES: Mental health services were measured using a dichotomous variable indicating whether mental health services were provided during the office visit or a referral made for: (1) counseling, including psychotherapy and other mental health counseling and/or (2) prescribing of psychotropic medications. RESULTS: Most patient office visits (70%) where a depression diagnosis was recorded also had co-occurring chronic physical conditions recorded. The presence of at least 1 physical chronic condition was associated with a 6% decrease in the probability of receiving any mental health services (P<0.05). There were no differences in service use by race/ethnicity after controlling for other factors. CONCLUSIONS: Additional research is needed on medical care delivery among patients with co-occurring health conditions, particularly as the health care system moves toward an integrated care model. PMID- 26147864 TI - Standardized data collection practices and the racial/ethnic distribution of hospitalized patients. AB - BACKGROUND: Although frequently used to track health care disparities, patient race/ethnicity data collected by hospitals can be unreliable, particularly for smaller minority groups. We sought to determine whether the racial/ethnic distribution of hospitalized patients shifted after implementation of a statewide initiative to standardize data collection practices. METHODS: We conducted a difference-in-differences analysis of the State Inpatient Databases to estimate changes in the proportion of patients identified as non-Hispanic white, non Hispanic black, Hispanic, Asian/Pacific Islander, and "other," before (2005-2006) and after (2008-2009) standardized practices were implemented in New Jersey relative to New York, a state with similar demographics but no changes to data collection. RESULTS: Among 12,552,702 hospital discharges, modest relative changes were noted in the proportion of patients identified as non-Hispanic white [+1.1%; 95% confidence interval (CI): +0.9 to +1.2] and non-Hispanic black (+1.6%; 95% CI: +1.1 to +2.1) in New Jersey that were attributed to its use of standardized data collection practices as compared with New York. Larger relative changes were noted in the proportion of patients identified as Hispanic (-7.1%; 95% CI: -7.8 to -6.4), Asian/Pacific Islander (+26.5%; 95% CI: +25.1 to +27.9), and "other" (-24.6%; 95% CI: -26.4 to -22.8). This pattern was largely consistent in analyses stratified by sex, age, and Major Diagnostic Category. CONCLUSIONS: Measurement of health care disparities fundamentally depends on the racial/ethnic categorization of individuals. By redistributing substantial proportions of patients across smaller minority groups, standardized data collection could lead to shifts in estimates of health care disparities for these rapidly growing populations. PMID- 26147865 TI - Weekend Discharges and Length of Stay Among Veterans Admitted for Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Discharge rates are substantially lower on weekends, though the impact on hospital length of stay (LOS) is not fully understood. OBJECTIVES: The primary objective was to examine the association of weekend discharges with hospital LOS. We also examined the association of weekend discharges with readmission, mortality, and postdischarge follow-up. RESEARCH DESIGN AND METHODS: A cohort study of 25,301 patients who were admitted to Veterans Affairs hospitals for chronic obstructive pulmonary disease during October 01, 2008-September 30, 2010, including 3845 patients discharged on the weekend (Saturday or Sunday) and 21,456 discharged on weekdays (Monday through Friday). RESULTS: There were significantly fewer discharges on the weekend (1922 per weekend day vs. 4279 per weekday, P<0.01). Inpatient status during the weekend at any point in hospitalization was associated with an increased LOS of 0.59 day [95% confidence interval (CI), 0.54-0.63 d]. Discharge on the weekend was not associated with increased odds of 30-day hospital readmission [odds ratio (OR)=1.00; 95% CI, 0.90 1.10] or lack of primary care follow-up visit within 14 days of discharge (OR=0.94; 95% CI, 0.85-1.03). However, weekend discharges were significantly associated with lower odds of mortality within 30 days after discharge (OR=0.80; 95% CI, 0.65-0.99). CONCLUSIONS: The presence of fewer weekend discharges was associated with significantly longer hospital lengths of stay. Weekend discharges were not associated with higher readmission rates and had lower rates of mortality compared with weekdays discharges. Identifying methods to increase weekend discharges may create an opportunity to improve hospital efficiency. PMID- 26147867 TI - Promising Practices for Achieving Patient-centered Hospital Care: A National Study of High-performing US Hospitals. AB - BACKGROUND: Patient-centered care is integral to health care quality, yet little is known regarding how to achieve patient-centeredness in the hospital setting. The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey measures patients' reports on clinician behaviors deemed by patients as key to a high-quality hospitalization experience. OBJECTIVES: We conducted a national study of hospitals that achieved the highest performance on HCAHPS to identify promising practices for improving patient-centeredness, common challenges met, and how those were addressed. RESEARCH DESIGN: We identified hospitals that achieved the top ranks or remarkable recent improvements on HCAHPS and surveyed key informants at these hospitals. Using quantitative and qualitative methods, we described the interventions used at these hospitals and developed an explanatory model for achieving patient-centeredness in hospital care. RESULTS: Fifty-two hospitals participated in this study. Hospitals used similar interventions that focused on improving responsiveness to patient needs, the discharge experience, and patient-clinician interactions. To improve responsiveness, hospitals used proactive nursing rounds (reported at 83% of hospitals) and executive/leader rounds (62%); for the discharge experience, multidisciplinary rounds (56%), postdischarge calls (54%), and discharge folders (52%) were utilized; for clinician-patient interactions, hospitals promoted specific desired behaviors (65%) and set behavioral standards (60%) for which employees were held accountable. Similar strategies were also used to achieve successful intervention implementation including HCAHPS data feedback, and employee and leader engagement and accountability. CONCLUSIONS: High-performing hospitals used a set of patient-centered care processes that involved both leaders and clinicians in ensuring that patient needs and preferences are addressed. PMID- 26147866 TI - Using machine learning to examine medication adherence thresholds and risk of hospitalization. AB - BACKGROUND: Quality improvement efforts are frequently tied to patients achieving >=80% medication adherence. However, there is little empirical evidence that this threshold optimally predicts important health outcomes. OBJECTIVE: To apply machine learning to examine how adherence to oral hypoglycemic medications is associated with avoidance of hospitalizations, and to identify adherence thresholds for optimal discrimination of hospitalization risk. METHODS: A retrospective cohort study of 33,130 non-dual-eligible Medicaid enrollees with type 2 diabetes. We randomly selected 90% of the cohort (training sample) to develop the prediction algorithm and used the remaining (testing sample) for validation. We applied random survival forests to identify predictors for hospitalization and fit survival trees to empirically derive adherence thresholds that best discriminate hospitalization risk, using the proportion of days covered (PDC). OUTCOMES: Time to first all-cause and diabetes-related hospitalization. RESULTS: The training and testing samples had similar characteristics (mean age, 48 y; 67% female; mean PDC=0.65). We identified 8 important predictors of all cause hospitalizations (rank in order): prior hospitalizations/emergency department visit, number of prescriptions, diabetes complications, insulin use, PDC, number of prescribers, Elixhauser index, and eligibility category. The adherence thresholds most discriminating for risk of all-cause hospitalization varied from 46% to 94% according to patient health and medication complexity. PDC was not predictive of hospitalizations in the healthiest or most complex patient subgroups. CONCLUSIONS: Adherence thresholds most discriminating of hospitalization risk were not uniformly 80%. Machine-learning approaches may be valuable to identify appropriate patient-specific adherence thresholds for measuring quality of care and targeting nonadherent patients for intervention. PMID- 26147868 TI - Evaluating Differential Item Functioning in the English General Practice Patient Survey: Comparison of South Asian and White British Subgroups. AB - OBJECTIVE: To evaluate two 5-item patient experience scales from the English General Practice (GP) Patient Survey for evidence of differential item functioning (DIF) given prior evidence of substantially worse reported health care experiences for South Asian compared with white British respondents. SETTING: A national survey of English patients' primary care experiences. METHOD: We used classic test and item response theory analysis to examine the possibility of DIF by patient ethnicity (South Asian, white British) after controlling for age, sex, health status, and quality of life in the English GP Patient Survey conducted in 2011/2012. RESULTS: Data were available for 873,051 respondents (818,219 white British/54,832 South Asian from 7795 English practices) who answered items relating to experiences of GP or nurses' care. Internal consistency reliability was high and similar for South Asian and white British patients. White British patients reported better average experiences than South Asians, but there was no evidence of DIF or different item response curves for white British and South Asian respondents, even in sensitivity analyses using matched samples. CONCLUSIONS: All communication items in the English GP Patient Survey showed similar South Asian versus white British differences, with no evidence of DIF. In contrast, differences due to scale use or expectations are typically variable rather than constant across scales. While other possibilities remain, these findings increase the likelihood that the observed negative responses of South Asian patients to this national survey reflect true differences in their experiences of care. PMID- 26147870 TI - Toxicological screening of human plasma by on-line SPE-HPLC-DAD: identification and quantification of acidic and neutral drugs. AB - A multi-analyte screening method for the quantification of 50 acidic/neutral drugs in human plasma based on on-line solid-phase extraction (SPE)-HPLC with photodiode array detection (DAD) was developed, validated and applied for clinical investigation. Acetone and methanol for protein precipitation, three different SPE materials (two electro-neutral, one strong anion-exchange, one weak cation-exchange) for on-line extraction, five HPLC-columns [one C18 (GeminiNX), two phenyl-hexyl (Gemini C6 -Phenyl, Kinetex Phenyl-Hexyl) and two pentafluorophenyl (LunaPFP(2), KinetexPFP)] for analytical separation were tested. For sample pre-treatment, acetone in the ratio 1:2 (plasma:acetone) showed a better baseline and fewer matrix peaks in the chromatogram than methanol. Only the strong anion-exchanger SPE cartridge (StrataX-A, pH 6) allowed the extraction of salicylic acid. Analytical separation was carried out on a Gemini C6 -Phenyl column (150 * 4.6 mm, 3 um) using gradient elution with acetonitrile-water 90:10 (v/v) and phosphate buffer (pH 2.3). Linear calibration curves with correlation coefficients r >= 0.9950/0.9910 were obtained for 46/four analytes. Additionally, this method allows the quantification of 23 analytes for therapeutic drug monitoring. Limits of quantitation ranged from 0.1 (amobarbital) to 23 mg/L (salicylic acid). Inter-/intra-day precisions of quality control samples (low/high) were better than 13% and accuracy (bias) ranged from -14 to 10%. A computer-assisted database was created for automated detection of 223 analytes of toxicological interests. Four cases of multi-drug intoxications are presented. PMID- 26147871 TI - Seronegative syphilis in a patient co-infected with HIV. PMID- 26147869 TI - Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains. AB - BACKGROUND: Although cutaneous ulcers (CU) in the tropics is frequently attributed to Treponema pallidum subspecies pertenue, the causative agent of yaws, Haemophilus ducreyi has emerged as a major cause of CU in yaws-endemic regions of the South Pacific islands and Africa. H. ducreyi is generally susceptible to macrolides, but CU strains persist after mass drug administration of azithromycin for yaws or trachoma. H. ducreyi also causes genital ulcers (GU) and was thought to be exclusively transmitted by microabrasions that occur during sex. In human volunteers, the GU strain 35000HP does not infect intact skin; wounds are required to initiate infection. These data led to several questions: Are CU strains a new variant of H. ducreyi or did they evolve from GU strains? Do CU strains contain additional genes that could allow them to infect intact skin? Are CU strains susceptible to azithromycin? METHODOLOGY/PRINCIPAL FINDINGS: To address these questions, we performed whole-genome sequencing and antibiotic susceptibility testing of 5 CU strains obtained from Samoa and Vanuatu and 9 archived class I and class II GU strains. Except for single nucleotide polymorphisms, the CU strains were genetically almost identical to the class I strain 35000HP and had no additional genetic content. Phylogenetic analysis showed that class I and class II strains formed two separate clusters and CU strains evolved from class I strains. Class I strains diverged from class II strains ~1.95 million years ago (mya) and CU strains diverged from the class I strain 35000HP ~0.18 mya. CU and GU strains evolved under similar selection pressures. Like 35000HP, the CU strains were highly susceptible to antibiotics, including azithromycin. CONCLUSIONS/SIGNIFICANCE: These data suggest that CU strains are derivatives of class I strains that were not recognized until recently. These findings require confirmation by analysis of CU strains from other regions. PMID- 26147872 TI - Recent Advances in Biocatalytic Promiscuity: Hydrolase-Catalyzed Reactions for Nonconventional Transformations. AB - Enzymes have emerged in recent decades as ideal catalysts for synthetic transformations under mild reaction conditions. Their capacity to accelerate a myriad of biotransformations with high levels of selectivity and broad substrate specificity including excellent atom economy has led to a current full recognition. The six classes of enzymes (oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases) possess outstanding abilities to perform specific modifications in target molecules. Nevertheless, in the last fifteen years, novel examples have appeared related to nonconventional processes catalyzed by various classes of biocatalysts. Amongst these, hydrolases have received special attention since they display remarkable activities in initially unexpected reactions such as carbon-carbon and carbon-heteroatom bond-formation reactions, oxidative processes and novel hydrolytic transformations. In this review, the main findings in this area will be disclosed, highlighting the catalytic properties of hydrolases not only to catalyze single processes but also multicomponent and tandem nonconventional reactions. PMID- 26147873 TI - How low is too low: Statin induced hemolysis. PMID- 26147874 TI - Patients' satisfaction with community treatment: a pilot cross-sectional survey adopting multiple perspectives. AB - ACCESSIBLE SUMMARY: Patients' satisfaction is scarcely studied within the context of community treatment for adolescents. Thus, this study adopts a multiple perspective on patients' satisfaction (including service users as well as staff members). The results highlighted that all informants (patients, foster carers in foster homes and professional caregivers from community treatment teams) perceived the patients to be satisfied, with foster carers reporting the highest patient satisfaction rate. Considering the patient satisfaction rate from multiple perspectives provides complementary understandings. Clinical outcomes and, specifically, a reduction in emotional difficulties were related to patient's satisfaction, but only from the patients' perspective. ABSTRACT: Community treatment (CT) teams in Switzerland provide care to patients who are unable to use regular child and adolescent mental health services (i.e. inpatient and outpatients facilities). No study has considered patients' self-rated satisfaction alongside with staff members' perspectives on patient satisfaction. Thus, adopting a cross-sectional survey design, we collected patients' satisfaction using the Client Satisfaction Questionnaire (CSQ-8), rated by multiple informants (patients, foster carers in foster homes and professional caregivers from CT teams). Professional caregivers assessed clinical outcomes using the Health of the Nation Outcome Scale for Children and Adolescents. The results indicated that all informants were satisfied with the community treatment teams. The satisfaction scores were not correlated across informants; however, the alleviation of emotional symptoms was correlated with patients' satisfaction. This study indicated that the use of a combined approach including the views of service users and professionals gives important complementary information. Finally, in our sample, lower emotional symptoms were linked to enhanced patient satisfaction. This study demonstrated the importance of considering multiple perspectives to obtain the most accurate picture of patients' satisfaction. Second, focusing on the reduction of emotional symptoms might lead to a higher degree of patients' satisfaction. PMID- 26147875 TI - Test-retest reliability of skeletal muscle oxygenation measurements during submaximal cycling exercise in patients with chronic heart failure. AB - The potential purpose of near-infrared spectroscopy (NIRS) as a clinical application in patients with chronic heart failure (CHF) is the identification of limitations in O2 delivery or utilization during exercise. The objective of this study was to evaluate absolute and relative test-retest reliability of skeletal muscle oxygenation measurements in patients with CHF. Thirty patients with systolic heart failure (left ventricular ejection fraction 31 +/- 8%) performed 6 min constant-load cycling tests at 80% of the anaerobic threshold (AT) with tissue saturation index (TSI) measurement at the vastus lateralis. Tests were repeated after 10 +/- 5 days to evaluate reliability. Absolute reliability was assessed with limits of agreement (LoA, expressed as bias +/- random error) and coefficients of variation (CV) for absolute values (LoA range: 0.4 +/- 6.2% to 0.6 +/- 7.9%; CV range: 4.7-7.1%), amplitudes (LoA range -0.5 +/- 5.8% to -0.7 +/ 6.8%; CV range: 26.2-42.1%), onset and recovery kinetics (mean response times; LoA 0.4 +/- 9.5 s, CV 23.5% and LoA -5.8 +/- 50.8 s, CV 67.4% respectively) and overshoot characteristics (CV range 45.7-208.6%). Relative reliability was assessed with intraclass correlation coefficients for absolute values (range 0.74 0.90), amplitudes (range 0.85-0.92), onset and recovery kinetics (0.53 and 0.51, respectively) and overshoot characteristics (range 0.17-0.74). In conclusion, absolute reliability of absolute values and onset kinetics seems acceptable for serial within-subject comparison, and as such, for evaluation of treatment effects. Absolute reliability of amplitudes and recovery kinetics is considered unsatisfactory. Relative reliability of absolute values and amplitudes is sufficient for purposes of physiological distinction between patients with CHF. Despite lower relative reliability, kinetics may still be useful for clinical application. PMID- 26147876 TI - Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis. AB - OBJECTIVES: Precursor Th17 lineage cells expressing CD161 are implicated in Rheumatoid Arthritis (RA) pathogenesis. CD4+CD161+ T-cells accumulate in RA joints and may acquire a non classical Th1 phenotype. The endogenous ligand for CD161 is lectin-like transcript 1 (LLT1). CD161/LLT1 ligation may co-stimulate T cell IFN-gamma production. We investigated the presence and identity of LLT1 expressing cells in RA synovial fluid (SF) and synovial tissue (ST). We also assessed levels of soluble LLT1 (sLLT1) in different phases of RA development. METHODS: Paired samples of peripheral blood mononuclear cells (MC) and SFMC (n = 14), digested ST cells (n = 4) and ST paraffin sections (n = 6) from late-stage RA were analyzed for LLT1 expression by flow cytometry and immunohistochemistry. sLLT1 was measured using a sandwich ELISA. Sera and SF from late-stage RA (n = 26), recently diagnosed RA patients (n = 39), seropositive arthralgia patients (SAP, n = 31), spondyloarthropathy patients (SpA, n = 26) and healthy controls (HC, n = 31) were assayed. RESULTS: In RA SF, LLT1 was expressed by a small proportion of monocytes. In RA ST, LLT1-expressing cells were detected in the lining, sublining layer and in areas with infiltrates. The LLT1 staining pattern overlapped with the CD68 staining pattern. FACS analysis of digested ST confirmed LLT1 expression by CD68+ cells. Elevated systemic sLLT1 was found in all patient groups. CONCLUSIONS: In RA joints, LLT1 is expressed by cells of the monocyte/macrophage lineage. Serum levels of sLLT1 were increased in all patient groups (patients with early- and late-stage RA, seropositive arthralgia and spondyloarthropathy) when compared to healthy subjects. PMID- 26147877 TI - Photochemical reactions of halogenated aromatic 1,3-diketones in solution studied by steady state, one- and two-color laser flash photolyses. AB - Photochemical processes of 4-tert-butyl-4'-methoxydibenzoylmethane (Avobenzone, AB), 4-phenylbenzoylbenzoyl-, 4-phenylbenzoyl-2'-furanyl- and 4-phenylbenzoyl-2' thenoylmethanes (PB@Ph, PB@F and PB@T, respectively) substituted with Br and Cl at the C2 position were studied by stationary and laser flash photolyses in solution. The absorption spectral features showed that the molecular structures of the halogenated diketones are in the keto forms while those of halogen-free diketones are in the enol forms. The excited singlet and triplet state energies were determined from the absorption and emission spectra. From the absorption spectral changes upon steady state photolysis of brominated diketones in ethanol, the corresponding halogen-free diketones were formed due to Br elimination being the major photochemical process. The determined quantum yields for the formation of the halogen-free diketones were independent of the amount of dissolved oxygen, indicating that the elimination process is an event in the excited singlet (S1) states. In contrast, from the observed absorption spectra obtained upon photolysis of chlorinated AB and PB@Ph, it was inferred that Norrish type I is the major photochemical reaction in the S1 states in acetonitrile. Chlorinated PB@F and PB@T were found to undergo Cl elimination in the S1 states in cyclohexane to form the corresponding halogen-free diketones. Laser photolysis studies of brominated AB in acetonitrile and ethanol provided a transient absorption spectrum ascribable to the Avobenzone radical (ABR) produced by debromination as the initial intermediate, followed by the AB formation in ethanol. The quenching rate constant of ABR by ethanol and the quantum yield of the AB formation via ABR were determined. These observations provided evidence that H-atom abstraction of ABR from ethanol is responsible for the AB formation. Conversely, laser flash photolysis of brominated and chlorinated PB@Ph, PB@F and PB@T demonstrated the formation of the triplet-triplet absorption spectra. No chemical reactions were found to occur in the triplet (T1) states. Two-color two laser photolysis studies were carried out on the T1 state of chlorinated PB@Ph, PB@F and PB@T, resulting in the formation of the corresponding halogen-free diketones. These observations confirmed the occurrence of Cl elimination in the highly excited triplet (Tn, n>= 2) states. Based on the computed bond dissociation energies for the C-halogen and C-C bonds, switching mechanisms of dehalogenation and alpha-cleavage were discussed. PMID- 26147878 TI - Mortality and Morbidity During Delivery Hospitalization Among Pregnant Women With Epilepsy in the United States. AB - IMPORTANCE: Between 0.3% and 0.5% of all pregnancies occur among women with epilepsy. Evidence suggests an increase in perinatal morbidity and mortality among women with epilepsy. However, these risks have not been quantified in large population-based samples. OBJECTIVE: To report on the risk for death and adverse outcomes at the time of delivery for women with epilepsy in the United States. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of pregnant women identified through delivery hospitalization records from the 2007-2011 Nationwide Inpatient Sample. From this representative sample of 20% of all US hospitals, we obtained a weighted sample of delivery hospitalizations from 69 385 women with epilepsy and 20 449 532 women without epilepsy. MAIN OUTCOMES AND MEASURES: Obstetrical outcomes including maternal death, cesarean delivery, length of stay, preeclampsia, preterm labor, and stillbirth. RESULTS: Women with epilepsy had a risk of death during delivery hospitalization of 80 deaths per 100 000 pregnancies, significantly higher than the 6 deaths per 100 000 pregnancies found among women without epilepsy (adjusted odds ratio [OR], 11.46 [95% CI, 8.64 15.19]). Women with epilepsy were also at a heightened risk for other adverse outcomes, including preeclampsia (adjusted OR, 1.59 [95% CI, 1.54-1.63]), preterm labor (adjusted OR, 1.54 [95% CI, 1.50-1.57]), and stillbirth (adjusted OR, 1.27 [95% CI, 1.17-1.38]), and had increased health care utilization, including an increased risk of cesarean delivery (adjusted OR, 1.40 [95% CI, 1.38-1.42]) and prolonged length of hospital stay (>6 days) among both women with cesarean deliveries (adjusted OR, 2.13 [95% CI, 2.03-2.23]) and women with vaginal deliveries (adjusted OR, 2.60 [95% CI, 2.41-2.80]). CONCLUSIONS AND RELEVANCE: Findings suggest that women with epilepsy are at considerably heightened risk for many adverse outcomes during their delivery hospitalization, including a more than 10-fold increased risk of death, and that increased clinical attention is imperative for these pregnancies. PMID- 26147880 TI - Pb2Ba3(BO3)3Cl: A Material with Large SHG Enhancement Activated by Pb-Chelated BO3 Groups. AB - Pb(II) has long been associated with lone pair activity and is often substituted in alkali earth metal borates to create new nonlinear optical (NLO) materials with enhanced second harmonic generation (SHG) capabilities. However, large enhancement in isomorphic Pb-free analogues is rare. Here we report a new NLO material Pb2Ba3(BO3)3Cl with a phase-matching SHG response approximately 3.2* that of KDP and 6* higher than its isomorphic compound Ba5(BO3)3Cl. We show that the enhanced SHG response originates from a unique edge-sharing connection between lead-oxygen polyhedra and boron-oxygen groups, making the dielectric susceptibility more easily affected by the external electric field of an incident photon. This understanding provides a route to identify systems that would benefit from SHG-active cation substitution in isomorphic structures that exhibit weak or null SHG responses. PMID- 26147879 TI - Involvement of central relaxin-3 signalling in sodium (salt) appetite. AB - NEW FINDINGS: What is the central question of this study? Sodium appetite is controlled by conserved neuronal transmitter-receptor systems. Here, we tested the contribution made by relaxin family peptide 3 receptor (RXFP3), the cognate G protein-coupled receptor for the neuropeptide relaxin-3. What is the main finding and its importance? Intracerebroventricular infusion of an RXFP3 antagonist reduced in a dose-dependent manner the volume of 0.3 m NaCl consumed by sodium depleted C57Bl/6J (wild-type) mice. This effect was absent in sodium-depleted Rxfp3 knockout mice, and RXFP3 antagonist infusion did not alter water consumption in wild-type mice subjected to multiple thirst tests, indicating both the pharmacological and the physiological specificity of observed effects. Our findings identify endogenous relaxin-3-RXFP3 signalling as a modulator of sodium appetite. Overconsumption of highly salted foods is common in Western diets and contributes significantly to metabolic disorders such as hypertension, renal dysfunction and diabetes. Sodium appetite, or the desire of terrestrial animals to seek and consume sodium-containing salts, is a behaviour mediated by a set of evolutionarily conserved neuronal systems. In these studies, we tested whether this instinctive behavioural drive is influenced by the G-protein-coupled relaxin family peptide 3 receptor (RXFP3), the cognate receptor for the neuropeptide relaxin-3, because relaxin-3-RXFP3 signalling can modulate arousal, motivation and ingestive behaviours. Intracerebroventricular (i.c.v.) infusion of the selective RXFP3 antagonist, R3(B1-22)R, reduced in a dose-dependent manner the volume of 0.3 m NaCl solution consumed when offered to sodium-depleted C57Bl/6J wild-type mice, relative to vehicle-treated control animals. Notably, i.c.v. R3(B1-22)R infusion did not alter 0.3 m NaCl consumption relative to vehicle in sodium-depleted Rxfp3 knockout mice, confirming the pharmacological specificity of this effect. Furthermore, i.c.v. R3(B1-22)R did not alter the volume of water consumed by wild-type mice in three tests where water drinking was the normal physiological response, suggesting that the ability of R3(B1-22)R to reduce activated salt appetite is specific and not due to a generalized reduction in drinking behaviour. These findings identify, for the first time, that endogenous relaxin-3-RXFP3 signalling is a powerful mediator of salt appetite in mice and further elucidate the functional role of the relaxin-3-RXFP3 system in the integrative control of motivated behaviours. PMID- 26147881 TI - Utilization of self-medication and prescription drugs among 15-year-old children from the German GINIplus birth cohort. AB - PURPOSE: The objective was to analyse paediatric drug utilization in relation to self-medication, prescription drugs, and the most reported therapeutic drug categories. METHODS: Data were collected for 3013 children on their utilization of drugs (4-week prevalence) from a German birth cohort study (GINIplus, 15-year follow-up) using a self-administered questionnaire. The drugs were grouped into over-the-counter drugs and prescription drugs, and were classified according to the anatomical therapeutic chemical classification system. Predictors were analysed using a logistic regression model with four independent variables (gender, study area, maternal education, and parental income). RESULTS: Some 69% of the reported 2489 drugs were over-the-counter drugs, and 31% were prescription drugs. The 4-week prevalence for using any type of drug was 41.0%. Drug categories with high prevalence rates of use were antiinflammatory drugs (10.3%), analgesics (7.1%), and antiallergics (5.0%). Factors associated with higher use of over-the-counter drugs were female gender (OR = 1.56, p < 0.0001) and higher maternal education (OR = 1.60, p = 0.0021; university degree vs. secondary high school). Maternal education was correlated with the use of prescribed or self medicated antiallergics (positive association) and contraceptives (negative association). The use of antibiotics, methylphenidate, and drugs for thyroid therapy was associated with lower parental income. CONCLUSION: The use of over the-counter drugs in 15-year-old children from the GINIplus birth cohort is very common and is predicted by socioeconomic factors such as maternal education. This has to be considered by health care managers when deciding about the exclusion of over-the-counter drugs (normally used for self-medication) from reimbursement or the deregulation of drug sales. PMID- 26147882 TI - Positron emission tomography-computed tomography can be useful in the early detection of metastases in primary mucinous carcinoma of the skin on the head and neck. AB - Primary mucinous carcinoma of the skin (PMCS) is a rare cutaneous malignant neoplasm; its regional node metastasis is also rare. Currently, positron emission tomography-computed tomography (PET-CT) is known to be a useful tool to search for early metastatic lesions in various carcinomas. However, PET-CT is not always specific for head and neck lesions because of physiological uptake in the brain, palatine tonsil, salivary gland, thyroid etc. Herein we present two cases of head and neck PMCS in which metastasis was diagnosed accurately by PET-CT. In these cases, nodal uptake of fluorodeoxy-d-glucose (FDG) histopathologically proved PMCS metastasis, verifying the utility of PET-CT in detail. A surgeon was involved in the verification to compare the histopathological manifestations with the imaging results. Histopathologically, two of 13 nodes were positive in case 1, and one of 41 nodes was positive in case 2. These positive nodes were completely in accordance with the FDG uptake findings with no false negative findings. In treating PMCS on head and neck lesions, PET-CT may be useful in the preoperative assessment when planning the extent of resection. PMID- 26147883 TI - Environmental Fate of the Herbicide Fluazifop-P-butyl and Its Degradation Products in Two Loamy Agricultural Soils: A Combined Laboratory and Field Study. AB - The herbicide fluazifop-P-butyl (FPB) is used against grasses in agricultural crops such as potato, oilseed rape, and sugar beet. Limited information is available in scientific literature on its environmental fate, therefore extensive monitoring at two agricultural test fields was combined with laboratory studies to determine leaching and the underlying degradation and sorption processes. Water samples from drains, suction cups, and groundwater wells showed leaching of the degradation products fluazifop-P (FP) and 2-hydroxy-5-trifluoromethyl-pyridin (TFMP) following FPB treatment. Laboratory experiments with soil from each field revealed a rapid degradation of FPB to FP. The degradation was almost exclusively microbial, and further biodegradation to TFMP occurred at a slower rate. Both degradation products were sorbed to the two soils to a small extent and were fairly persistent to degradation during the two-month incubation period. Together, the field and laboratory results from this study showed that the biodegradation of FPB in loamy soils gave rise to the production of two major degradation products that sorbed to a small extent. In this study, both degradation products leached to drainage and groundwater during precipitation. It is therefore recommended that these degradation products be included in programs monitoring water quality in areas with FPB use. PMID- 26147884 TI - Turning Peptide Ligands into Small-Molecule Inhibitors of Protein-Protein Interactions. AB - Proline makeover: Truncation and extensive chemical modification of a peptide ligand yielded a biologically active, cell-permeable, peptidomimetic, small molecule inhibitor of a protein-protein interaction. A key step in this transformation was the replacement of a tetraproline motif by two conformationally constrained diproline units that retain the molecule's PPII helix. PMID- 26147885 TI - Correction: Transgenic Fatal Familial Insomnia Mice Indicate Prion Infectivity Independent Mechanisms of Pathogenesis and Phenotypic Expression of Disease. PMID- 26147886 TI - Implication of Leptin-Signaling Proteins and Epstein-Barr Virus in Gastric Carcinomas. AB - We investigated the clinicopathological implications of leptin-signaling proteins and Epstein-Barr virus (EBV)-infection status in gastric carcinomas. Immunohistochemistry for leptin signalling-related proteins (leptin, leptin receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha), and in situ hybridization for EBV-encoded small RNAs was performed in 343 cases of gastric carcinomas. The siRNA against leptin-receptor was transfected into three stomach cancer cell lines, and western blot for caspase 3 was performed. The TNM stage was a prognostic factor in all 343 patients, and was negatively correlated with expression of leptin, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha (P < 0.05). Leptin receptor expression was correlated with poor survival in 207 patients of the advanced gastric cancer (AGC) subgroup, 139 of the Lauren diffuse group, and in 160 patients with lymph node metastasis (P < 0.05, respectively). Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased. Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor. Among, leptin signaling-related proteins, expressions of leptin-receptor and mTOR were different between EBV-positive subgroup and EBV-negative subgroup (P < 0.05, respectively). In conclusion, leptin-signaling proteins and EBV status show different significance on patient survival, according to subsets of gastric carcinomas. The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC. Each leptin signaling-related protein may be differently involved in carcinogenesis of EBV-negative and EBV-positive subsets. PMID- 26147887 TI - Self-Organization of Spatio-Temporal Hierarchy via Learning of Dynamic Visual Image Patterns on Action Sequences. AB - It is well known that the visual cortex efficiently processes high-dimensional spatial information by using a hierarchical structure. Recently, computational models that were inspired by the spatial hierarchy of the visual cortex have shown remarkable performance in image recognition. Up to now, however, most biological and computational modeling studies have mainly focused on the spatial domain and do not discuss temporal domain processing of the visual cortex. Several studies on the visual cortex and other brain areas associated with motor control support that the brain also uses its hierarchical structure as a processing mechanism for temporal information. Based on the success of previous computational models using spatial hierarchy and temporal hierarchy observed in the brain, the current report introduces a novel neural network model for the recognition of dynamic visual image patterns based solely on the learning of exemplars. This model is characterized by the application of both spatial and temporal constraints on local neural activities, resulting in the self organization of a spatio-temporal hierarchy necessary for the recognition of complex dynamic visual image patterns. The evaluation with the Weizmann dataset in recognition of a set of prototypical human movement patterns showed that the proposed model is significantly robust in recognizing dynamically occluded visual patterns compared to other baseline models. Furthermore, an evaluation test for the recognition of concatenated sequences of those prototypical movement patterns indicated that the model is endowed with a remarkable capability for the contextual recognition of long-range dynamic visual image patterns. PMID- 26147888 TI - Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection Related Cancers--Hepatocellular Carcinoma and Cervical Cancer. AB - Caspase recruitment domain family, member 8 (CARD8) can coordinate innate and adaptive immune responses and sensitize cells to apoptosis, which may participate in tumorigenesis of virus-induced hepatocellular carcinoma (HCC) and cervical cancer. By bioinformatics analyses, we identified several single nucleotide polymorphisms (SNPs) within a new identified long non-coding RNA (lncRNA) as expression quantitative trait loci (eQTLs) for CARD8. In this study, we therefore hypothesized that CARD8 eQTLs SNPs within lncRNA may influence the risk of HCC and cervical cancer. We performed two independent case-control studies of 1,300 cases with HBV-positive HCC and 1,344 normal controls, together with 1,486 cervical cancer patients and 1,536 control subjects to test the association between eQTLs SNP (rs7248320) for CARD8 and the risk of HCC and cervical cancer. The variant genotype of rs7248320 was significantly associated with increased risk of HCC and cervical cancer [GG vs. AA/GA: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.03-1.61, P = 0.028 for HCC; adjusted OR = 1.34, 95% CI = 1.09-1.66, P = 0.006 for cervical cancer]. Moreover, the effect of rs7248320 on cervical cancer risk was more prominent in premenopausal women. Further interactive analysis detected a significantly multiplicative interaction between rs7248320 and menopausal status on cervical cancer risk (P = 0.018). These findings suggest that CARD8 eQTLs SNP may serve as a susceptibility marker for virus-related HCC and cervical cancer. PMID- 26147889 TI - Protection by the NO-Donor SNAP and BNP against Hypoxia/Reoxygenation in Rat Engineered Heart Tissue. AB - In vitro assays could replace animal experiments in drug screening and disease modeling, but have shortcomings in terms of functional readout. Force-generating engineered heart tissues (EHT) provide simple automated measurements of contractile function. Here we evaluated the response of EHTs to hypoxia/reoxygenation (H/R) and the effect of known cardiocytoprotective molecules. EHTs from neonatal rat heart cells were incubated for 24 h in EHT medium. Then they were subjected to 180 min hypoxia (93% N2, 7% CO2) and 120 min reoxygenation (40% O2, 53% N2, 7% CO2), change of medium and additional follow-up of 48 h. Time-matched controls (40% O2, 53% N2, 7% CO2) were run for comparison. The following conditions were applied during H/R: fresh EHT medium (positive control), the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 10(-7), 10( 6), 10(-5) M) or the guanylate cyclase activator brain type natriuretic peptide (BNP, 10(-9), 10(-8), 10(-7) M). Frequency and force of contraction were repeatedly monitored over the entire experiment, pH, troponin I (cTnI), lactate dehydrogenase (LDH) and glucose concentrations measured in EHT medium. Beating activity of EHTs in 24 h-medium ceased during hypoxia, partially recovered during reoxygenation and reached time-control values during follow-up. H/R was accompanied by a small increase in LDH and non-significant increase in cTnI. In fresh medium, some EHTs continued beating during hypoxia and all EHTs recovered faster during reoxygenation. SNAP and BNP showed small but significant protective effects during reoxygenation. EHTs are applicable to test potential cardioprotective compounds in vitro, monitoring functional and biochemical endpoints, which otherwise could be only measured by using in vivo or ex vivo heart preparations. The sensitivity of the model needs improvement. PMID- 26147892 TI - Drugs for Insomnia. PMID- 26147890 TI - YoeB toxin is activated during thermal stress. AB - Type II toxin-antitoxin (TA) modules are thought to mediate stress-responses by temporarily suppressing protein synthesis while cells redirect transcription to adapt to environmental change. Here, we show that YoeB, a ribosome-dependent mRNase toxin, is activated in Escherichia coli cells grown at elevated temperatures. YoeB activation is dependent on Lon protease, suggesting that thermal stress promotes increased degradation of the YefM antitoxin. Though YefM is efficiently degraded in response to Lon overproduction, we find that Lon antigen levels do not increase during heat shock, indicating that another mechanism accounts for temperature-induced YefM proteolysis. These observations suggest that YefM/YoeB functions in adaptation to temperature stress. However, this response is distinct from previously described models of TA function. First, YoeB mRNase activity is maintained over several hours of culture at 42 degrees C, indicating that thermal activation is not transient. Moreover, heat-activated YoeB does not induce growth arrest nor does it suppress global protein synthesis. In fact, E. coli cells proliferate more rapidly at elevated temperatures and instantaneously accelerate their growth rate in response to acute heat shock. We propose that heat-activated YoeB may serve a quality control function, facilitating the recycling of stalled translation complexes through ribosome rescue pathways. PMID- 26147891 TI - Computational Inferences of the Functions of Alternative/Noncanonical Splice Isoforms Specific to HER2+/ER-/PR- Breast Cancers, a Chromosome 17 C-HPP Study. AB - This study was conducted as a part of the Chromosome-Centric Human Proteome Project (C-HPP) of the Human Proteome Organization. The main objective is to identify and evaluate functionality of a set of specific noncanonical isoforms expressed in HER2-neu positive, estrogen receptor negative (ER-), and progesterone receptor negative (PR-) breast cancers (HER2+/ER-/PR- BC), an aggressive subtype of breast cancers that cause significant morbidity and mortality. We identified 11 alternative splice isoforms that were differentially expressed in HER2+/ER-/PR- BC compared to normal mammary, triple negative breast cancer and triple positive breast cancer tissues (HER2+/ER+/PR+). We used a stringent criterion that differentially expressed noncanonical isoforms (adjusted p value < 0.05) and have to be expressed in all replicates of HER2+/ER-/PR- BC samples, and the trend in differential expression (up or down) is the same in all comparisons. Of the 11 protein isoforms, six were overexpressed in HER2+/ER-/PR- BC. We explored possible functional roles of these six proteins using several complementary computational tools. Biological processes including cell cycle events and glycolysis were linked to four of these proteins. For example, glycolysis was the top ranking functional process for DMXL2 isoform 3, with a fold change of 27 compared to just two for the canonical protein. No previous reports link DMXL2 with any metabolic processes; the canonical protein is known to participate in signaling pathways. Our results clearly indicate distinct functions for the six overexpressed alternative splice isoforms, and these functions could be specific to HER2+/ER-/PR- tumor progression. Further detailed analysis is warranted as these proteins could be explored as potential biomarkers and therapeutic targets for HER2+/ER-/PR- BC patients. PMID- 26147893 TI - Liletta--A Third Levonorgestrel-Releasing IUD. PMID- 26147894 TI - Ryanodex--A New Dantrolene Formulation for Malignant Hyperthermia. PMID- 26147895 TI - Eliglustat (Cerdelga)--An Oral Drug for Gaucher Disease. PMID- 26147896 TI - What is the role of mid-urethral slings in the management of stress incontinence in women? PMID- 26147897 TI - In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug. AB - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC's resistance. The development of novel therapies against HCC is thus urgently required. The cyclin dependent kinase (CDK) pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested in vitro. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene in vivo in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg) exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg). Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history of safe human use, our discovery of fluspirilene as a potential anti-HCC drug may present an immediately applicable clinical therapy. PMID- 26147898 TI - Evaluation of measures of impairment in real and simulated driving: Results from a randomized, placebo-controlled study. AB - OBJECTIVE: Standard deviation of lateral position (SDLP) is often the primary outcome in experimental studies on impaired driving. However, other measures may be easier and more practical to obtain and reflect a broader range of driving related behaviors. We wanted to assess the validity and sensitivity of a range of measures in a driving simulator as well as during real driving and compare these to SDLP. METHODS: Twenty healthy male volunteers undertook 6 driving trials each, 3 in a regular car on a closed track resembling rural road conditions and 3 in a simulator with an identical driving scenario. Ethanol was used as impairing substance due to its well-characterized effects on driving. The subjects were tested sober and at blood alcohol concentrations (BAC) of approximately 0.5 and 0.9 g/L. We explored dose-response relationships between BAC and a range of driving-related measures, as well as their BAC-dependent effect sizes. RESULTS: In simulator driving, ethanol intake increased steering wheel reversal frequency, steering wheel movement measures, average speed, standard deviation of speed, and pedal use frequency. At the test track, only steering wheel movement and standard deviation of speed were significantly correlated to BAC. Likewise, reaction to unexpected incidents and observance of red traffic lights were adversely affected by ethanol in the simulator but not at the test track. Whereas SDLP showed a relatively large effect size that was similar in simulated and real driving, all other measures demonstrated smaller effect sizes, with less pronounced BAC effects on the test track than in the simulator. CONCLUSIONS: The results suggest that the driving-related measures explored in this study are less sensitive to alcohol-mediated driving impairment than SDLP, especially during real (test track) driving. The discrepancy in effect sizes between simulated and real driving may imply low external validity of these measures in simulator studies. PMID- 26147899 TI - Turkevich in New Robes: Key Questions Answered for the Most Common Gold Nanoparticle Synthesis. AB - This contribution provides a comprehensive mechanistic picture of the gold nanoparticle synthesis by citrate reduction of HAuCl4, known as Turkevich method, by addressing five key questions. The synthesis leads to monodisperse final particles as a result of a seed-mediated growth mechanism. In the initial phase of the synthesis, seed particles are formed onto which the residual gold is distributed during the course of reaction. It is shown that this mechanism is a fortunate coincidence created by a favorable interplay of several chemical and physicochemical processes which initiate but also terminate the formation of seed particles and prevent the formation of further particles at later stages of reaction. Since no further particles are formed after seed particle formation, the number of seeds defines the final total particle number and therefore the final size. The gained understanding allows illustrating the influence of reaction conditions on the growth process and thus the final size distribution. PMID- 26147900 TI - Interleukin-28B polymorphisms and interferon gamma inducible protein-10 serum levels in seronegative occult hepatitis C virus infection. AB - Polymorphisms upstream interleukin (IL)-28B gene and serum levels of interferon gamma inducible protein-10 (IP-10) are associated with spontaneous and treatment induced hepatitis C virus (HCV) clearance. Patients with seronegative occult HCV infection are anti-HCV and serum HCV-RNA negative but have viral RNA in liver and abnormal values of liver enzymes. We examined if the rs12979860 polymorphism of IL-28B and serum IP-10 levels differ between chronic and seronegative occult CV infection. IL-28B polymorphism was determined with allele specific TaqMan probes in total DNA isolated from peripheral blood mononuclear cells and IP-10 by an enzyme-linked immunosorbent assay in serum from 99 patients with seronegative occult HCV infection and 130 untreated patients with chronic hepatitis C. IL-28B genotypes were also determined in 54 healthy volunteers. Prevalence of the IL-28B CC genotype was significantly higher in seronegative occult HCV infection (52/99; 52.5%) than in chronic hepatitis C (32/130; 24.6%, P < 0.0001) or healthy controls (19/54: 32.5%, P = 0.039). Among patients with seronegative occult HCV infection, HCV-RNA load in liver was significantly lower in those with the IL-28B CC genotype than in those with CT + TT genotypes (2.8 * 10(5) +/- 5.8 * 10(4) vs. 4.1 * 10(5) +/- 5.9 * 10(4) copies/MUg of total RNA respectively; P = 0.023). Mean serum IP-10 levels were significantly lower in patients with seronegative occult HCV infection than in patients with chronic hepatitis C (160.8 +/- 17.9 vs. 288.7 +/- 13.3 pg/ml respectively; P < 0.0001). These findings suggest that the host immune response plays an important role in seronegative occult HCV infection in comparison with chronic hepatitis C. PMID- 26147901 TI - Self-compassion, attitudes to ageing and indicators of health and well-being among midlife women. AB - OBJECTIVES: Attitudes to ageing exert a powerful influence on health and well being, yet surprisingly little research has examined factors that contribute to the formation of these attitudes. The aim of this study was to consider the potential role of self-compassion in predicting attitudes to ageing, which in turn contribute to positive and negative mental well-being and self-reported health. METHOD: This was a cross-sectional study using data from 517 midlife women aged between 40 and 60. Structural equation modelling was used to examine the relationships between self-compassion, three facets of attitudes to ageing and well-being outcomes. RESULTS: Together, self-compassion and attitudes to ageing explained between 36% and 67% of the variance in well-being. Self compassion was a strong predictor of attitudes towards psychosocial loss, physical change and psychological growth (beta range: .22-.51). Furthermore, the relationship between self-compassion and well-being outcomes was partially mediated by attitudes to physical change. CONCLUSION: Self-compassion may be a modifiable internal resource to promote healthy attitudes to ageing in midlife, when ageing becomes personally relevant. Moreover, attitudes towards physical change may help explain how self-compassion promotes well-being among midlife women. PMID- 26147902 TI - The Inner Nuclear Membrane Protein Src1 Is Required for Stable Post-Mitotic Progression into G1 in Aspergillus nidulans. AB - How membranes and associated proteins of the nuclear envelope (NE) are assembled specifically and inclusively around segregated genomes during exit from mitosis is incompletely understood. Inner nuclear membrane (INM) proteins play key roles by providing links between DNA and the NE. In this study we have investigated the highly conserved INM protein Src1 in Aspergillus nidulans and have uncovered a novel cell cycle response during post mitotic formation of G1 nuclei. Live cell imaging indicates Src1 could have roles during mitotic exit as it preferentially locates to the NE abscission points during nucleokinesis and to the NE surrounding forming daughter G1 nuclei. Deletion analysis further supported this idea revealing that although Src1 is not required for interphase progression or mitosis it is required for stable post-mitotic G1 nuclear formation. This conclusion is based upon the observation that in the absence of Src1 newly formed G1 nuclei are structurally unstable and immediately undergo architectural modifications typical of mitosis. These changes include NPC modifications that stop nuclear transport as well as disassembly of nucleoli. More intriguingly, the newly generated G1 nuclei then cycle between mitotic- and interphase-like states. The findings indicate that defects in post-mitotic G1 nuclear formation caused by lack of Src1 promote repeated failed attempts to generate stable G1 nuclei. To explain this unexpected phenotype we suggest a type of regulation that promotes repetition of defective cell cycle transitions rather than preventing progression past the defective cell cycle transition. We suggest the term "reboot regulation" to define this mode of cell cycle regulation. The findings are discussed in relationship to recent studies showing the Cdk1 master oscillator can entrain subservient oscillators that when uncoupled cause cell cycle transitions to be repeated. PMID- 26147904 TI - Language Development of Individuals Who Require Aided Communication: Reflections on State of the Science and Future Research Directions. AB - Language acquisition theories differ in the importance they assign to production as a learning mechanism. This review summarizes some of the theoretical issues linked to this debate and considers their implications for children with severe speech and physical impairments. The unique aspects of the language-learning contexts of these children are explored. Drawing largely on papers published within the journal Augmentative and Alternative Communication, this review summarizes features of language development that have been described over the past 3 decades and considers how these findings might illuminate our understanding of language development across both spoken and aided modalities. Implications for assessment, intervention and for further research are suggested. PMID- 26147903 TI - Proteomic analysis of integrin-associated complexes from mesenchymal stem cells. AB - PURPOSE: Multipotent mesenchymal stem cells (MSCs) have the capability to differentiate down adipocyte, osteocyte and chondrocyte lineages and as such offer a range of potential therapeutic applications. The composition and stiffness of the extracellular matrix (ECM) environment that surrounds cells dictates their transcriptional programme, thereby affecting stem cell lineage decision-making. Cells sense force via linkages between themselves and their microenvironment, and this is transmitted by integrin receptors and associated adhesion signalling complexes. To identify regulators of MSC force sensing, we sought to catalogue MSC integrin-associated adhesion complex composition. EXPERIMENTAL DESIGN: Adhesion complexes formed by MSCs plated on the ECM ligand fibronectin were isolated and characterised by MS. Identified proteins were interrogated by comparison to a literature-based reference set of cell adhesion related components and using ontological and protein-protein interaction network analyses. RESULTS: Adhesion complex-specific proteins in MSCs were identified that comprised predominantly cell adhesion-related adaptors and actin cytoskeleton regulators. Furthermore, LIM domain-containing proteins in MSC adhesion complexes were highlighted, which may act as force-sensing components. CONCLUSION AND CLINICAL RELEVANCE: These data provide a valuable resource of information regarding the molecular connections that link integrins and adhesion signalling in MSCs, and as such may present novel opportunities for therapeutic intervention. PMID- 26147905 TI - Managing paediatric death in the emergency department. AB - Death of a child in an emergency department is a rare occurrence, but one with significant impact on the family and staff involved. The rarity means few emergency department clinicians feel 'expert' in the overall management process. However, most have some knowledge and experience which can be augmented by collaborating with other health professionals. By exploring some of the main management issues and challenges for the emergency department, key aspects of care are identified for emergency department clinicians to consider in reviewing local procedures and guidelines. PMID- 26147906 TI - Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging. AB - Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early stage cancer diagnosis. Gadolinium (Gd)(III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high X-ray attenuation coefficient, is an ideal contrast agent candidate for X-ray-based CT imaging. Gd metal-organic framework (MOF) nanoparticles with tunable size, high Gd(III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multimodal imaging probes. PMID- 26147907 TI - Primary testicular Ph-positive B lymphoblastic lymphoma: an unusual presentation and review. AB - Primary testicular B-lymphoblastic lymphoma is a rare entity. Primary testicular Ph-positive B lymphoblastic lymphoma was not reported before. We reported a 27 year-old man with primary testicular Ph-positive B lymphoblastic lymphoma, for which fluorescent in-situ hybridization (FISH) for the Philadelphia chromosome was not performed at the initial hospitalization. The patient showed manifestation of Ph-positive acute lymphoblastic leukemia at relapse. In this report, we reviewed the current literature about primary testicular B lymphoblastic lymphoma, Ph-positive lymphoma and Ph-positive clone evolution. This report has 3 meanings. First: This is first report on primary testicular Ph positive B lymphoblastic lymphoma. Second: This shows the importance of cytogenics for lymphoma treatment. Third: This implies Philadelphia-positive subclone evolution. PMID- 26147909 TI - Biologics in dermatology: adverse effects. AB - Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. PMID- 26147908 TI - iStent with Phacoemulsification versus Phacoemulsification Alone for Patients with Glaucoma and Cataract: A Meta-Analysis. AB - BACKGROUND: Minimally invasive glaucoma surgeries (MIGS) have attracted significant attention, as they have been reported to lower intra-ocular pressure (IOP) and have an excellent safety profile. The iStent is an example of a minimally invasive glaucoma device that has received particular attention due to its early and wide spread utilization. There is a growing body of evidence supporting its use at the time of phacoemulsification to help lower IOP. However, it is still not clear how much of the IOP lowering effect can be attributed to the iStent, the crystalline lens extraction or both when inserted concurrently at the time of phacoemulsification. This has been an important issue in understanding its potential role in the glaucoma management paradigm. PURPOSE: To conduct a systematic review and meta-analysis comparing the IOP lowering effect of iStent insertion at the time of phacoemulsification versus phacoemulsification alone for patients with glaucoma and cataracts. METHODS: A systematic review was conducted utilizing various databases. Studies examining the IOP lowering effect of iStent insertion in combination with phacoemulsification, as well as studies examining the IOP lowering effect of phacoemulsification alone were included. Thirty-seven studies, reporting on 2495 patients, met the inclusion criteria. The percentage reduction in IOP (IOPR%) and mean reduction in topical glaucoma medications after surgery were determined. The standardized mean difference (SMD) was computed as a measure of the treatment effect for continuous outcomes taking into account heterogeneity. Fixed-effect and random-effect models were applied. RESULTS: A 4% IOP reduction (IOPR%) from baseline occurred following phacoemulsification as a solo procedure compared to 9% following an iStent implant with phacoemulsification, and 27% following 2 iStents implants with phacoemulsification. Compared with cataract extraction alone, iStent with phacoemulsification resulted in significant reduction in the post-operative IOP (IOPR%) (SMD = -0.46, 95% CI: [-0.87, -0.06]). A weighted mean reduction in the number of glaucoma medications per patient was 1.01 following phacoemulsification alone compared to 1.33 after one iStent implant with phacoemulsification, and 1.1 after 2 iStent implants with phacoemulsification. Compared to cataract extraction alone, iStent with cataract extraction showed a significant decrease in the number of glaucoma medications (SMD = -0.65, 95% CI: [-1.18, -0.12]). Funnel plots suggested the absence of publication bias. CONCLUSION: Both iStent implantation with concurrent phacoemulsification and phacoemulsification alone result in a significant decrease in IOP and topical glaucoma medications. In terms of both reductions, iStent with phacoemulsification significantly outperforms phacoemulsification alone. PMID- 26147910 TI - Prevalence of coeliac disease in idiopathic hypoparathyroidism and effect of gluten-free diet on calcaemic control. AB - BACKGROUND: Patients with idiopathic hypoparathyroidism (IH) require variable doses of calcium and 1-alpha-(OH)D. The reasons for such variability are not clear. As autoimmune mechanisms may play a role in IH, there is a possibility of coexistent coeliac disease with calcium/vitamin D malabsorption. OBJECTIVE: We assessed the prevalence of coeliac disease and antitissue transglutaminase autoantibodies (anti-tTGAbs) in IH and analysed the effect of a gluten-free diet on calcaemic control. METHOD: A total of 171 patients with IH and 126 healthy controls were screened for anti-tTGAb. IH patients with anti-tTGAb >20 RU/ml underwent duodenoscopy and intestinal biopsy; those with biopsy-proven coeliac disease were followed up on a gluten-free diet. RESULTS: Eleven of 171 (6.4%) patients with IH and seven of 126 (5.6%) controls had anti-tTGAb (P = 0.81). There was no difference in the clinical and biochemical parameters at diagnosis and during long-term follow-up of 7.2 +/- 4.8 year (mean serum total calcium = 1.88 +/- 0.16 vs 1.82 +/- 0.36 mmol/l, P = 0.52; phosphorus = 1.81 +/- 0.17 vs 1.87 +/- 0.36 mmol/l, P = 0.53) in IH patients with and without anti-tTGAb. Although CaSRAb positivity was comparable in the two groups, IH patients with anti-tTGAb had higher TPOAb positivity (45.5% vs 12.8%, P = 0.02). Coeliac disease was diagnosed in only 2/9 patients with IH on biopsy, both of whom showed improved calcaemic control with a gluten-free diet. CONCLUSION: The prevalence of coeliac autoimmunity (6.4%) and coeliac disease (1.2%) in patients with IH seems to be similar to that in the general population. Notwithstanding this modest prevalence, it is important to be aware of the potential occurrence of coeliac disease with IH and the beneficial effect of a gluten-free diet on calcium control. PMID- 26147911 TI - Management of Demented Patients with Urinary Incontinence: A Case Study. AB - OBJECTIVE: To assess whether a demented patient with urinary incontinence (UI) could learn to use an adapted version of timed voiding (i.e., instead of being led by a caregiver, the patient learns to perform timed voiding by herself). Indeed, UI affects a large number of patients with dementia and creates a substantial burden to the caregiver. UI is the most common complaint at the time of institutionalization and it is often the cause of premature institutionalization. Timed voiding is a promising intervention, but one whose effectiveness remains to be demonstrated. Additionally, timed voiding has the disadvantage of being constraining for caregivers, requiring them to be present to stimulate the patient to urinate at each of the scheduled occasions. METHOD: The present intervention required the patient to learn (1) to associate an auditory signal from a timer to the action of urination, (2) to reprogram the timer, using the spaced retrieval technique. An ABAB paradigm was used to assess the effectiveness of this program to eliminate urinary accidents. RESULTS: The results of the intervention showed that the use of the timer was effective in helping the patient to reduce her urinary leaks from 1.5 diurnal accidents per week to zero during four months. CONCLUSION: UI in patients with dementia seems treatable. Such intervention could contribute to delay institutionalization of patients with dementia through maintaining their autonomy and reducing the burden of caregivers. PMID- 26147912 TI - Development and Characterization of the Arterial Windkessel and Its Role During Left Ventricular Assist Device Assistance. AB - Modeling of the cardiovascular system is challenging, but it has the potential to further advance our understanding of normal and pathological conditions. Morphology and function are closely related. The arterial system provides steady blood flow to each organ and damps out wave fluctuations as a consequence of intermittent ventricular ejection. These actions can be approached separately in terms of mathematical relationships between pressure and flow. Lumped parameter models are helpful for the study of the interactions between the heart and the arterial system. The arterial windkessel model still plays a significant role despite its limitations. This review aims to discuss the model and its modifications and derive the fundamental equations by applying electric circuits theory. In addition, its role during left ventricular assist device assistance is explored and discussed in relation to rotary blood pumps. PMID- 26147913 TI - Management of acute breathlessness in the person with chronic refractory breathlessness. AB - PURPOSE OF REVIEW: The purpose of this review is to synthesize the current literature on classification and management of acute breathlessness that occurs in patients who are living with chronic refractory breathlessness related to cancer, cardiopulmonary, or neuromuscular disease. RECENT FINDINGS: In the context of chronic refractory breathlessness, acute breathlessness can be classified as either episodic breathlessness or breathlessness crisis. Episodic breathlessness is characterized by the severity, duration, and predictability of the symptom, and by the presence or absence of a trigger such as exertion, emotion, or an environmental factor. Breathlessness crisis is more sustained, occurs at rest, and overwhelms the patient's and caregivers' coping abilities, similar to the nontriggered unpredictable types of episodic breathlessness. Treatment of acute breathlessness focuses on alleviating the episode as quickly as possible without escalating medical intervention that may not be consistent with the patient's treatment preferences. SUMMARY: Attention to breathlessness in the published literature has increased exponentially in the past two decades. The challenge is now to translate the research findings into relief of symptoms, suffering, and distress in those who suffer from acute and chronic breathlessness because of chronic illness. PMID- 26147914 TI - A review of the 2014 English Language publications pertinent to the treatment of invasive bladder cancer by radiotherapy. AB - PURPOSE OF REVIEW: This is a review of select 2014 English language publications in the domain of bladder conserving treatment for patients with localized invasive urothelial vesical cancer. RECENT FINDINGS: The intention is to summarize the avenues of research being pursued to improve the success of this management strategy. SUMMARY: Directions being investigated are enhancement to bladder tumor control, amelioration of treatment toxicity, and individualization of treatment. Although the results reported are clearly beneficial, what is of more value is the appreciation of the multipronged direction of the research being undertaken to firmly ensconce this organ preserving strategy within the clinical armamentarium that urooncologists can bring to bear in caring for the individual patient diagnosed with bladder cancer. PMID- 26147915 TI - Psychosocial issues experienced by young women with breast cancer: the minority group with the majority of need. AB - PURPOSE OF REVIEW: The ways in which biological, social, and psychological factors characteristically unfold and interact for young women with breast cancer yields complex and acute challenges that are not clearly understood by all healthcare professionals. Better knowledge of the unique needs of young women with breast cancer would assist in matching younger women with the right services at the right time. RECENT FINDINGS: Younger women (<50 years) represent a minority of breast cancer cases, yet they tend to be overrepresented with respect to demonstrating the poorest psychosocial adjustment during and following treatment. Concerns most frequently reported in this age group pertained to body image, sexual functioning, fertility, relationships, fear of cancer recurrence, and caring for children; failure of healthcare providers to initiate conversations to educate women about treatment side effects early on and/or safely discuss sensitive issues; lack of widespread availability of professional psychosocial programs that are tailored to the unique needs of this age group. SUMMARY: Young women with breast cancer are at greater risk for psychosocial adjustment problems, yet their needs are often overlooked. Proactive discussions by healthcare providers early on in treatment, and referrals to relevant services as part of standard care are needed to mitigate younger women's concerns and reduce the likelihood of problems becoming longstanding. PMID- 26147916 TI - Parallel transmission pulse design with explicit control for the specific absorption rate in the presence of radiofrequency errors. AB - PURPOSE: A new framework for the design of parallel transmit (pTx) pulses is presented introducing constraints for local and global specific absorption rate (SAR) in the presence of errors in the radiofrequency (RF) transmit chain. METHODS: The first step is the design of a pTx RF pulse with explicit constraints for global and local SAR. Then, the worst possible SAR associated with that pulse due to RF transmission errors ("worst-case SAR") is calculated. Finally, this information is used to re-calculate the pulse with lower SAR constraints, iterating this procedure until its worst-case SAR is within safety limits. RESULTS: Analysis of an actual pTx RF transmit chain revealed amplitude errors as high as 8% (20%) and phase errors above 3 degrees (15 degrees ) for spokes (spiral) pulses. Simulations show that using the proposed framework, pulses can be designed with controlled "worst-case SAR" in the presence of errors of this magnitude at minor cost of the excitation profile quality. CONCLUSION: Our worst case SAR-constrained pTx design strategy yields pulses with local and global SAR within the safety limits even in the presence of RF transmission errors. This strategy is a natural way to incorporate SAR safety factors in the design of pTx pulses. Magn Reson Med 75:2493-2504, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26147917 TI - Multitarget super-resolution microscopy with high-density labeling by exchangeable probes. AB - We have developed a multitarget super-resolution microscopy technique called image reconstruction by integrating exchangeable single-molecule localization (IRIS). IRIS uses protein fragment-based probes that directly associate with and dissociate from their targets over durations on the order of tens of milliseconds. By integrating single-molecule localization and sequential labeling, IRIS enables unprecedented labeling density along multiple cellular structures. IRIS can be used to discern the area-specific proximity between cytoskeletal components and focal adhesions within a single cell. PMID- 26147918 TI - Single-molecule spectroscopy of protein conformational dynamics in live eukaryotic cells. AB - Single-molecule methods have become widely used for quantifying the conformational heterogeneity and structural dynamics of biomolecules in vitro. Their application in vivo, however, has remained challenging owing to shortcomings in the design and reproducible delivery of labeled molecules, the range of applicable analysis methods, and suboptimal cell culture conditions. By addressing these limitations in an integrated approach, we demonstrate the feasibility of probing protein dynamics from milliseconds down to the nanosecond regime in live eukaryotic cells with confocal single-molecule Forster resonance energy transfer (FRET) spectroscopy. We illustrate the versatility of the approach by determining the dimensions and submicrosecond chain dynamics of an intrinsically disordered protein; by detecting even subtle changes in the temperature dependence of protein stability, including in-cell cold denaturation; and by quantifying the folding dynamics of a small protein. The methodology opens possibilities for assessing the effect of the cellular environment on biomolecular conformation, dynamics and function. PMID- 26147919 TI - Dose Optimization in TOF-PET/MR Compared to TOF-PET/CT. AB - PURPOSE: To evaluate the possible activity reduction in FDG-imaging in a Time-of Flight (TOF) PET/MR, based on cross-evaluation of patient-based NECR (noise equivalent count rate) measurements in PET/CT, cross referencing with phantom based NECR curves as well as initial evaluation of TOF-PET/MR with reduced activity. MATERIALS AND METHODS: A total of 75 consecutive patients were evaluated in this study. PET/CT imaging was performed on a PET/CT (time-of-flight (TOF) Discovery D 690 PET/CT). Initial PET/MR imaging was performed on a newly available simultaneous TOF-PET/MR (Signa PET/MR). An optimal NECR for diagnostic purposes was defined in clinical patients (NECRP) in PET/CT. Subsequent optimal activity concentration at the acquisition time ([A]0) and target NECR (NECRT) were obtained. These data were used to predict the theoretical FDG activity requirement of the new TOF-PET/MR system. Twenty-five initial patients were acquired with (retrospectively reconstructed) different imaging times equivalent for different activities on the simultaneous PET/MR for the evaluation of clinically realistic FDG-activities. RESULTS: The obtained values for NECRP, [A]0 and NECRT were 114.6 (+/- 14.2) kcps (Kilocounts per second), 4.0 (+/- 0.7) kBq/mL and 45 kcps, respectively. Evaluating the NECRT together with the phantom curve of the TOF-PET/MR device, the theoretical optimal activity concentration was found to be approximately 1.3 kBq/mL, which represents 35% of the activity concentration required by the TOF-PET/CT. Initial evaluation on patients in the simultaneous TOF-PET/MR shows clinically realistic activities of 1.8 kBq/mL, which represent 44% of the required activity. CONCLUSION: The new TOF-PET/MR device requires significantly less activity to generate PET-images with good-to excellent image quality, due to improvements in detector geometry and detector technologies. The theoretically achievable dose reduction accounts for up to 65% but cannot be fully translated into clinical routine based on the coils within the FOV and MR-sequences applied at the same time. The clinically realistic reduction in activity is slightly more than 50%. Further studies in a larger number of patients are needed to confirm our findings. PMID- 26147920 TI - Anterior ocular abnormalities of captive Asian elephants (Elephas maximus indicus) in Thailand. AB - OBJECTIVE: To survey and classify anterior ocular abnormalities in 1478 captive Asian elephants (Elephas maximus indicus) in six regions of Thailand. METHODS: Anterior ocular examination was performed in both eyes (n = 2956) of 1478 elephants selected from the annual health check program involving 2958 animals within six regions of Thailand from January to November 2013. Lesions were described and compared between age and gender. RESULTS: A total of 17.83% (527/2956) of examined eyes from 24.97% (369/1478) of examined elephants had anterior ocular abnormalities. The most common lesions in these examined eyes were frothy ocular discharge (5.85%), corneal edema (5.31%), and conjunctivitis (5.18%). In addition, epiphora, phthisis bulbi, other corneal abnormalities, anterior uveitis, and lens abnormalities were noted. Almost all lesions increased in frequency with age (P < 0.01). CONCLUSIONS: Regular ophthalmic examination in elephants should be included in their annual health check program. Early detection and treatment of any ocular abnormality may avoid the development of subsequent irreversible ocular pathology. PMID- 26147921 TI - What Determines the Perception of Fairness Regarding Household Division of Labor between Spouses? AB - Married women often undertake a larger share of housework in many countries and yet they do not always perceive the inequitable division of household labor to be "unfair." Several theories have been proposed to explain the pervasive perception of fairness that is incongruent with the observed inequity in household tasks. These theories include 1) economic resource theory, 2) time constraint theory, 3) gender value theory, and 4) relative deprivation theory. This paper re-examines these theories with newly available data collected on Japanese married women in 2014 in order to achieve a new understanding of the gendered nature of housework. It finds that social comparison with others is a key mechanism that explains women's perception of fairness. The finding is compatible with relative deprivation theory. In addition to confirming the validity of the theory of relative deprivation, it further uncovers that a woman's reference groups tend to be people with similar life circumstances rather than non-specific others. The perceived fairness is also found to contribute to the sense of overall happiness. The significant contribution of this paper is to explicate how this seeming contradiction of inequity in the division of housework and the perception of fairness endures. PMID- 26147922 TI - Biofumigation on Post-Harvest Diseases of Fruits Using a New Volatile-Producing Fungus of Ceratocystis fimbriata. AB - A variety of volatile organic compounds (VOCs) produced by Ceratocystis fimbriata have strong bioactivity against a wide range of fungi, bacteria and oomycetes. Mycelial growth, conidial production, and spore germination of fungi and oomycetes were significantly inhibited after exposure to cultures of C. fimbriata, and colony formation of bacteria was also inhibited. Two post-harvest diseases, peach brown rot caused by Monilinia fructicola and citrus green mold caused by Penicillium digitatum, were controlled during a 4-day storage by enclosing wound-inoculated fruits with 10 standard diameter Petri plate cultures of C. fimbriata in a 15 L box. The fruits were freshly inoculated at onset of storage and the cultures of C. fimbriata were 6 days old. Percentage of control was 92 and 97%, respectively. After exposure to C. fimbriata VOCs, severely misshapen hyphae and conidia of these two post-harvest pathogens were observed by scanning electron microscopy, and their pathogenicity was lost or greatly reduced. PMID- 26147923 TI - Randomized Cross-Sectional Study to Compare HIV-1 Specific Antibody and Cytokine Concentrations in Female Genital Secretions Obtained by Menstrual Cup and Cervicovaginal Lavage. AB - INTRODUCTION: Optimizing methods for genital specimen collection to accurately characterize mucosal immune responses is a priority for the HIV prevention field. The menstrual cup (MC) has been proposed as an alternative to other methods including cervicovaginal lavage (CVL), but no study has yet formally compared these two methods. METHODS: Forty HIV-infected, antiretroviral therapy-naive women from the CAPRISA 002 acute HIV infection cohort study were randomized to have genital fluid collected using the MC with subsequent CVL, or by CVL alone. Qualitative data, which assessed levels of comfort and acceptability of MC using a 5-point Likert scale, was collected. Luminex multiplex assays were used to measure HIV-specific IgG against multiple gene products and 48 cytokines. RESULTS: The majority (94%) of participants indicated that insertion, wearing and removal of the MC was comfortable. Nineteen MCs with 18 matching, subsequent CVLs and 20 randomized CVLs were available for analysis. Mucosal IgG responses against four HIV-antigens were detected in 99% of MCs compared to only 80% of randomized CVLs (p = 0.029). Higher specific antibody activity and total antibodies were observed in MCs compared to CVL (all p<0.001). In MCs, 42/48 (88%) cytokines were in the detectable range in all participants compared to 27/48 (54%) in CVL (p<0.001). Concentrations of 22/41 cytokines (53.7%) were significantly higher in fluid collected by MC. Both total IgG (r = 0.63; p = 0.005) and cytokine concentrations (r = 0.90; p<0.001) correlated strongly between MC and corresponding post-MC CVL. CONCLUSIONS: MC sampling improves the detection of mucosal cytokines and antibodies, particularly those present at low concentrations. MC may therefore represent an ideal tool to assess immunological parameters in genital secretions, without interfering with concurrent collection of conventional CVL samples. PMID- 26147924 TI - The heritable path of human physical performance: from single polymorphisms to the "next generation". AB - Human physical performance is a complex multifactorial trait. Historically, environmental factors (e.g., diet, training) alone have been unable to explain the basis of all prominent phenotypes for physical performance. Therefore, there has been an interest in the study of the contribution of genetic factors to the development of these phenotypes. Support for a genetic component is found with studies that shown that monozygotic twins were more similar than were dizygotic twins for many physiological traits. The evolution of molecular techniques and the ability to scan the entire human genome enabled association of several genetic polymorphisms with performance. However, some biases related to the selection of cohorts and inadequate definition of the study variables have complicated the already difficult task of studying such a large and polymorphic genome, often resulting in inconsistent results about the influence of candidate genes. This review aims to provide a critical overview of heritable genetic aspects. Novel molecular technologies, such as next-generation sequencing, are discussed and how they can contribute to improving understanding of the molecular basis for athletic performance. It is important to ensure that the large amount of data that can be generated using these tools will be used effectively by ensuring well-designed studies. PMID- 26147925 TI - Association of MnSOD AA Genotype with the Progression of Prostate Cancer. AB - PURPOSE: To investigate whether manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with the clinical significance of prostate cancer. MATERIALS AND METHODS: Prostates were obtained from 194 deceased men 45 years or older who did not have a history of prostate cancer. Serial sections and histological examinations of the prostate were performed. The MnSOD genotypes of the specimens were determined by polymerase chain reaction restriction fragment length polymorphism analysis. RESULTS: Of the 194 men, 31 and 26 had clinically insignificant and significant prostate cancer. Clinically significant cancer comprised 29% and 58% of the cancers in men <70 and >70 years old, respectively. The age-specific proportion of significant cancer significantly increased with the advance of age (p<0.001). MnSOD AA, as compared with the other genotypes (VA and VV together), was associated with significant prostate cancer across all ages, odds ratio (OR) 2.34, 95% confidence interval (CI) 0.99-5.49, and in men older than 69 years (OR 4.89, 95% CI 1.51-15.8), but not in men younger than 70 years. The genotype was not associated with clinically insignificant cancer regardless of age. The comparison between significant and insignificant cancer, the OR (95% CI) for MnSOD AA was 5.04 (1.05-24.2) (sensitivity 0.57, specificity 0.78, positive predictive value 0.78) in men older than 69 years. CONCLUSIONS: MnSOD polymorphism is strongly associated with the clinical significance of prostate cancer in men older than 69 years, but not in men younger than 70 years suggesting that oxidative stress may be involved in the progression of the disease. MnSOD may be a clinically useful marker to predict the potential of progression of prostate cancer. PMID- 26147926 TI - Virus-induced wheezing in infants aged 12-24 months and bronchiolitis in infants under 6 months are different clinical entities. PMID- 26147927 TI - Microscale Adaptation of In Vitro Transcription/Translation for High-Throughput Screening of Natural Product Extract Libraries. AB - Novel antimicrobials that effectively inhibit bacterial growth are essential to fight the growing threat of antibiotic resistance. A promising target is the bacterial ribosome, a 2.5 MDa organelle susceptible to several biorthogonal modes of action used by different classes of antibiotics. To promote the discovery of unique inhibitors, we have miniaturized a coupled transcription/translation assay using E. coli and applied it to screen a natural product library of ~30 000 extracts. We significantly reduced the scale of the assay to 2 MUL in a 1536-well plate format and decreased the effective concentration of costly reagents. The improved assay returned 1327 hits (4.6% hit rate) with %CV and Z' values of 8.5% and 0.74, respectively. This assay represents a significant advance in molecular screening, both in miniaturization and its application to a natural product extract library, and we intend to apply it to a broad array of pathogenic microbes in the search for novel anti-infective agents. PMID- 26147928 TI - Synergistic Effect of Sodium Chlorite and Edible Coating on Quality Maintenance of Minimally Processed Citrus grandis under Passive and Active MAP. AB - Edible coating has been an innovation within the bioactive packaging concept. The comparative analysis upon the effect of edible coating, sodium chlorite (SC) and their combined application on quality maintenance of minimally processed pomelo (Citrus grandis) fruits during storage at 4 degrees C was conducted. Results showed that the combination of edible coating and SC dipping delayed the microbial development whereas the sole coating or dipping treatment was less efficient. The synergetic application of edible coating and SC treatment under modified atmosphere packaging (MAP, 10% O2 , 10% CO2 ) was able to maintain the total soluble solids level and ascorbic acid content, while reduce the weight loss as well as development of mesophiles and psychrotrophs. Nonetheless, the N, O-carboxymethyl chitosan solely coated samples showed significantly higher level of weight loss during storage with comparison to the untreated sample. Furthermore, the combined application of edible coating and SC dipping under active MAP best maintained the sensory quality of minimally processed pomelo fruit during storage. PMID- 26147929 TI - Implementation process of all periodontal competences and assessments as proposed in the 2010 European consensus meeting into the existing local undergraduate curriculum. AB - AIM: To report on our implementation process within the existing local curriculum of all periodontal competences and assessments as proposed in the 2010 European consensus meeting. MATERIAL AND METHOD: In 2011, a workshop for all teaching staff at the Department of Periodontology, ACTA, an education and assessment blueprint, was developed to test for missing education and assessment of European competences, divided into seven domains. This was repeated in 2013. An oral evaluation of the staff followed both meetings. RESULTS: It appeared that eight of 58 (14%) European competences were not taught, and 21 (35%) competences were not assessed. After evaluation of the results on the actual curriculum and the assessment programme, shared decisions were made about how to teach and assess the missing competences within the local periodontal educational programme. The second workshop in 2013 revealed still 8 (14%) competences were not taught and 8 (14%) competences were not assessed. Staff appreciated the used method of validation; it gave insight and an overview of the curriculum. The existence of the European consensus report for undergraduate periodontal education, based on seven domains, has been instrumental and essential. CONCLUSION: The development of a blueprint from the education programme and concomitant assessment methods in periodontology by participating teaching staff gives a validation and appreciation of the curriculum and will improve the quality of education and assessment. It is advised that for quality control of the curriculum, dental schools could do this exercise for all their specialties if European consensus reports exist. PMID- 26147930 TI - ASHA-Life Intervention Perspectives Voiced by Rural Indian Women Living With AIDS. AB - In this focus group study, we explored the experiences of 16 rural women living with AIDS (WLA) who participated in the Asha-Life (AL) intervention to gain an understanding of the environmental, psychosocial, and cultural impact of the AL on their lives. Four themes emerged among AL participants: (a) the importance of tangible support, (b) need for social support, (c) ongoing challenges to accessing antiretroviral therapy (ART), and (d) perspectives on future programs. Our research findings support the development of future programs targeting mother child dyads which emphasize nutritional knowledge, while reducing barriers to receiving ART, and physical, emotional, and financial support. PMID- 26147931 TI - Molecular Identification of Atlantic Bluefin Tuna (Thunnus thynnus, Scombridae) Larvae and Development of a DNA Character-Based Identification Key for Mediterranean Scombrids. AB - The Atlantic bluefin tuna, Thunnus thynnus, is a commercially important species that has been severely over-exploited in the recent past. Although the eastern Atlantic and Mediterranean stock is now showing signs of recovery, its current status remains very uncertain and as a consequence their recovery is dependent upon severe management informed by rigorous scientific research. Monitoring of early life history stages can inform decision makers about the health of the species based upon recruitment and survival rates. Misidentification of fish larvae and eggs can lead to inaccurate estimates of stock biomass and productivity which can trigger demands for increased quotas and unsound management conclusions. Herein we used a molecular approach employing mitochondrial and nuclear genes (CO1 and ITS1, respectively) to identify larvae (n = 188) collected from three spawning areas in the Mediterranean Sea by different institutions working with a regional fisheries management organization. Several techniques were used to analyze the genetic sequences (sequence alignments using search algorithms, neighbour joining trees, and a genetic character-based identification key) and an extensive comparison of the results is presented. During this process various inaccuracies in related publications and online databases were uncovered. Our results reveal important differences in the accuracy of the taxonomic identifications carried out by different ichthyoplanktologists following morphology-based methods. While less than half of larvae provided were bluefin tuna, other dominant taxa were bullet tuna (Auxis rochei), albacore (Thunnus alalunga) and little tunny (Euthynnus alletteratus). We advocate an expansion of expertise for a new generation of morphology-based taxonomists, increased dialogue between morphology-based and molecular taxonomists and increased scrutiny of public sequence databases. PMID- 26147933 TI - What's your motivation to be pregnant? Relations between motives for parenthood and women's prenatal functioning. AB - Prenatal psychological adjustment is a critical predictor of postnatal maternal adjustment, which, in turn, relates to a child's psychological development. As such, it is important to examine possible correlates of women's psychological functioning during pregnancy. Grounded in self-determination theory (Deci & Ryan, 2000), the present research investigated the link between women's motives for having a child and prenatal maternal psychological adjustment. Specifically, in a sample of 208 pregnant women, we examined the relation between women's intensity (i.e., quantity) and quality of motivation for having a child and both women's social adjustment (i.e., relationship satisfaction) and personal well-being (i.e., vitality and depressive symptoms). Further, we examined psychological need satisfaction as an explanatory mechanism underlying these associations. Results showed that both intensity and quality of motivation related, either directly or indirectly via psychological need satisfaction, to women's personal well-being and relationship satisfaction during pregnancy. PMID- 26147932 TI - Physiological linkage in couples and its implications for individual and interpersonal functioning: A literature review. AB - Do partners' levels of physiological arousal become linked in close relationships? The term physiological linkage describes covariation between people in their moment-to-moment physiological states. The current review presents a conceptual framework to guide research on linkage in romantic relationships and discusses the potential implications of being linked. Evidence of linkage was found across a broad range of physiological indices and in a variety of contexts, including during laboratory-based conflict and in daily life. Four hypotheses regarding how linkage relates to individual and interpersonal functioning are evaluated: (a) coactivation of the sympathetic nervous system or the hypothalamic-pituitary adrenal axis is "bad," (b) moderate physiological linkage is "just right," (c) physiological linkage is problematic if the individual or couple is overloaded, and (d) the implications of physiological linkage depend on the emotional context. We found partial support for the first hypothesis and determined that more research is needed to evaluate the remaining hypotheses. Linkage in cortisol was negatively associated with relationship satisfaction; but, at the same time, linkage in multiple systems was positively associated with indices of relationship connectedness, such as the amount of time spent together and the ability to identify the emotions of one's partner. These results suggest that linkage may confer benefits but also may put couples at risk if they become entrenched in patterns of conflict or stress. With research in this area burgeoning in recent years, this review indicates that linkage is a promising construct with applications for interventions targeting individual health and couple functioning. PMID- 26147934 TI - Transactional processes in children born preterm: Influences of mother-child interactions and parenting stress. AB - This prospective, longitudinal study examined the transactional relations among perceived maternal parenting stress, maternal insensitivity, and child behavior across toddlerhood through age 6 within families of a child born preterm. A sample of 173 mother-child dyads were followed from just before the infant was discharged from the neonatal intensive care unit to 6 years of age, with observational measurements of maternal insensitivity and child noncompliance (24 and 36 months), maternal self-reports of perceived parenting stress (24 months, 36 months, 6 years), and maternal reports of child externalizing behavior at 6 years. Results indicated that maternal insensitivity at 36 months significantly mediated the relation between parenting stress at 24 months and externalizing behaviors at 6 years. Parenting stress was also directly associated with child noncompliance at 36 months and with child externalizing behavior at 6 years. Neonatal risk was associated with increased maternal insensitivity at 24 months, but also decreased parenting stress at 24 months. No significant "child effects" from child behavior to either maternal insensitivity or parenting stress were found. Parenting stress appears to play a critical role for children born preterm, and it is associated with children's behavior both directly and through its influence on parenting. The role of neonatal risk needs continued investigation, as families traditionally considered to be at lower risk may still face significant challenges. PMID- 26147935 TI - The Meaning of Emotional Overinvolvement in Early Development: Prospective Relations With Child Behavior Problems. AB - Emotional overinvolvement (EOI) in parents' Five Minute Speech Samples (FMSSs; Magana-Amato, 1993) is thought to measure overconcern and enmeshment with one's child. Although related to maladaptive outcomes in studies of adult children, FMSS EOI evidences varied relations with behavior problems in studies with young children. These mixed findings may indicate that certain FMSS EOI criteria reflect inappropriate and excessive involvement with adult children, but do not indicate maladaptive processes when parenting younger children. Thus, this study evaluated relations of each FMSS EOI criterion with changes in child behavior problems from preschool to first grade in a community sample of 223 child-mother dyads (47.98% female; Wave 1 M(age) 49.08 months; 56.50% Hispanic/Latina). Maternal FMSS EOI ratings were obtained at Wave 1, and independent examiners rated child externalizing and internalizing behavior problems at Wave 1 and again 2 years later. Path analyses indicated that both the self sacrifice/overprotection (SSOP) and statements of attitude (SOAs) FMSS EOI criteria predicted increased externalizing problems. In contrast, excessive detail and exaggerated praise were not related to child externalizing behavior problems, and Emotional Display was not evident in this sample. None of the FMSS EOI criteria evidenced significant relations with internalizing behavior problems. Multigroup comparisons indicated that the effect of SOAs on externalizing behavior problems was significant for boys but not for girls, and there were no significant group differences by race/ethnicity. These findings point to the salience of SSOP and SOAs for understanding the developmental significance of EOI in early development. PMID- 26147936 TI - Dyadic coping mediates the association of sanctification with marital satisfaction and well-being. AB - Some studies suggest that the sanctification of marriage, or considering marriage sacred, is related to positive marital outcomes (e.g., marital satisfaction, conflict resolution). However, the mechanisms explaining this association have not been sufficiently investigated. In the current study, we analyzed supportive dyadic coping as a potential mediator of the relation between marriage sanctity and marital satisfaction, as well as between marriage sanctity and well-being. Self-reported data were collected from 215 Romanian couples (N = 430) belonging to the Christian Orthodox religion. Analyses using the common fate model indicate that supportive dyadic coping mediates both the relation between sanctification and marital satisfaction, as well as the relation between sanctification and well being. These findings suggest that sanctification increases support provided to the partner, which in turn is positively related to marital satisfaction and well being at the dyadic level. PMID- 26147937 TI - Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study. AB - OBJECTIVE: To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice. METHODS: Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure. RESULTS: This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]). CONCLUSION: LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not. PMID- 26147938 TI - Emotion Recognition Ability Test Using JACFEE Photos: A Validity/Reliability Study of a War Veterans' Sample and Their Offspring. AB - Emotion recognition is very important for social interaction. Several mental disorders influence facial emotion recognition. War veterans and their offspring are subject to an increased risk of developing psychopathology. Emotion recognition is an important aspect that needs to be addressed in this population. To our knowledge, no test exists that is validated for use with war veterans and their offspring. The current study aimed to validate the JACFEE photo set to study facial emotion recognition in war veterans and their offspring. The JACFEE photo set was presented to 135 participants, comprised of 62 male war veterans and 73 war veterans' offspring. The participants identified the facial emotion presented from amongst the possible seven emotions that were tested for: anger, contempt, disgust, fear, happiness, sadness, and surprise. A loglinear model was used to evaluate whether the agreement between the intended and the chosen emotions was higher than the expected. Overall agreement between chosen and intended emotions was 76.3% (Cohen kappa = 0.72). The agreement ranged from 63% (sadness expressions) to 91% (happiness expressions). The reliability by emotion ranged from 0.617 to 0.843 and the overall JACFEE photo set Cronbach alpha was 0.911. The offspring showed higher agreement when compared with the veterans (RR: 41.52 vs 12.12, p < 0.001), which confirms the construct validity of the test. The JACFEE set of photos showed good validity and reliability indices, which makes it an adequate instrument for researching emotion recognition ability in the study sample of war veterans and their respective offspring. PMID- 26147939 TI - Serum levels of alpha-1 acid glycoprotein and pentraxin 3 in patients with Behcet's disease and relationship with disease activity. AB - BACKGROUND: To evaluate the relationship between disease activity and levels of alpha 1-acid glycoprotein and pentraxin 3 in patients with Behcet's disease (BD). METHODS: Forty-eight patients with BD and 29 age- and gender-matched healthy control subjects were included in the study. Serum pentraxin 3 levels were measured using enzyme-linked immunosorbent assay (ng/ml), and alpha 1-acid glycoprotein levels were measured using nephelometry (mg/dl). Disease activity was assessed using the BD Current Activity Form (BDCAF). RESULTS: Serum alpha-1 acid glycoprotein levels were significantly higher in patients with BD compared to the control group (P = 0.048). There were no significant differences between two groups in terms of levels of pentraxin 3 (P = 0.697). According to Pearson's analysis, alpha 1-acid levels are significantly positively correlated with erythrocyte sedimentation rate, C-reactive protein, and skin lesions and arthritis of BDCAF scores. Pentraxin 3 levels did not correlate with erythrocyte sedimentation rate, C-reactive protein, or any domains of BDCAF scores. CONCLUSION: The results of the present study demonstrate that serum levels of alpha-1 acid glycoprotein were significantly higher in patients with BD relative to the control group. Alpha-1 acid glycoprotein is greatly associated with skin lesions and arthritis in patients with BD. We did not find high serum levels of PTX3 in patients with BD compared to healthy controls, and pentraxin 3 is not associated with disease activity in BD. PMID- 26147941 TI - 99mTc-phytate as a diagnostic probe for assessing inflammatory reaction in malignant tumors. AB - OBJECTIVE: Once administered intravenously, technetium-99m (99mTc)-labeled phytate binds to calcium in the serum and behaves as a nanoparticle. On the basis of the high permeability of the tumor vasculature, 99mTc-phytate is expected to leak and accumulate specifically in inflammatory cells. The aim of this study was to evaluate the potential of 99mTc-phytate in assessing the degree of inflammation in Ehrlich solid tumors in mice. MATERIALS AND METHODS: 99mTc phytate was prepared by adding pertechnetate to a solution containing phytic acid and stannous chloride. The blood half-life of this particle following intravenous injection was determined using blood samples from healthy animals, whereas its size was measured by photon correlation spectroscopy. Scintigraphic imaging and biodistribution studies were carried out in tumor-bearing mice at 30 min and 2 h after injection. RESULTS: The average size of the particles was in the range of 200 nm, suggesting that they are capable of passively passing through fenestrations in tumor vessels, which are 200-2000 nm in size. The blood half life for 99mTc-phytate was found to be 2.1 min, a result that is in agreement with previous studies. Data from tumor-bearing mice showed high tumor uptake at 2 h after 99mTc-phytate administration. As a result, a high tumor-to-muscle ratio was achieved (T/M = 25.9 +/- 7.54). CONCLUSION: These findings indicate that 99mTc-sodium phytate has promising properties for identifying the type of tumor. This approach will have significant implications for characterizing tumor biology and treatment of malignant lesions. PMID- 26147940 TI - Transcriptomic Responses of the Heart and Brain to Anoxia in the Western Painted Turtle. AB - Painted turtles are the most anoxia-tolerant tetrapods known, capable of surviving without oxygen for more than four months at 3 degrees C and 30 hours at 20 degrees C. To investigate the transcriptomic basis of this ability, we used RNA-seq to quantify mRNA expression in the painted turtle ventricle and telencephalon after 24 hours of anoxia at 19 degrees C. Reads were obtained from 22,174 different genes, 13,236 of which were compared statistically between treatments for each tissue. Total tissue RNA contents decreased by 16% in telencephalon and 53% in ventricle. The telencephalon and ventricle showed >= 2x expression (increased expression) in 19 and 23 genes, respectively, while only four genes in ventricle showed <= 0.5x changes (decreased expression). When treatment effects were compared between anoxic and normoxic conditions in the two tissue types, 31 genes were increased (>= 2x change) and 2 were decreased (<= 0.5x change). Most of the effected genes were immediate early genes and transcription factors that regulate cellular growth and development; changes that would seem to promote transcriptional, translational, and metabolic arrest. No genes related to ion channels, synaptic transmission, cardiac contractility or excitation-contraction coupling changed. The generalized expression pattern in telencephalon and across tissues, but not in ventricle, correlated with the predicted metabolic cost of transcription, with the shortest genes and those with the fewest exons showing the largest increases in expression. PMID- 26147943 TI - Exploring why people with SMI smoke and why they may want to quit: baseline data from the SCIMITAR RCT. AB - ACCESSIBLE SUMMARY: People with severe mental ill health are up to three times more likely to smoke than other members of the general population. Life expectancy in this client group is reduced by up to 30 years, and smoking is the single most important cause of premature death. The aim of this study was to explore why people with severe mental ill health smoked and why they might want to stop smoking or cut down on the amount of cigarettes that they smoked. The study found that people with severe mental ill health are motivated to cut down or stop smoking, and this is mainly due to concerns about their own health. The reasons people gave for smoking were to relieve stress, to help relax and for something to do when they are bored. Health professionals should offer evidence supported smoking cessation therapy to people with severe mental ill health. In addition to standard National Health Service smoking cessation treatments such as pharmacotherapy and behavioural support. Practitioners should help people with serious mental ill health to identify meaningful activities to relieve boredom and challenge any incorrect beliefs they hold that smoking helps relaxation and relieves stress. ABSTRACT: Smoking is the single most preventable cause of premature mortality for people with serious mental ill health (SMI). Yet little is known about the reasons why service users smoke or what their motivations for quitting might be. The aim of this paper is to explore smoking behaviours, reasons for smoking and motivations for cutting down/stopping smoking in individuals with SMI who expressed an interest in cutting down or stopping smoking. Prior to randomization, the smoking behaviours and motivations for wanting to cut down or stop smoking of participants in a randomized trial were systematically assessed. Participant's primary reasons for continuing to smoke were that they believed it helped them to cope with stress, to relax and relieve boredom. Participant's main motivations for wanting to cut down or stop smoking were related to concerns for their own health. Previous attempts to stop smoking had often been made alone without access to evidence supported smoking cessation therapy. Future recommendations include helping people with SMI to increase their activity levels to relieve boredom and inspire confidence in their ability to stop smoking and challenging beliefs that smoking aids relaxation and relieves stress. PMID- 26147942 TI - Taenia solium Human Cysticercosis: A Systematic Review of Sero-epidemiological Data from Endemic Zones around the World. AB - BACKGROUND: Taenia solium cysticercosis is a zoonotic neglected disease responsible for severe health disorders such as seizures and death. Understanding the epidemiology of human cysticercosis (HCC) in endemic regions will help to expose critical information about the transmission of the disease, which could be used to design efficient control programs. This review gathered serological data on apparent prevalence of T. solium circulating antigens and/or seroprevalence of T. solium antibodies, apparent prevalence of human taeniasis and risk factors for HCC from endemic communities in order to understand the differences in exposure to the parasite and active infections with T. solium metacestodes in endemic areas around the world. METHODS: Three databases were used to search sero epidemiological data from community-based studies conducted between 1989 and 2014 in cysticercosis endemic communities worldwide. The search focused on data obtained from T. solium circulating antigen detection by monoclonal antibody based sandwich ELISA and/or T. solium antibody seroprevalence determined by Enzyme-linked Immunoelectrotransfer Blot (EITB). A meta-analysis was performed per continent. PRINCIPAL FINDINGS: A total of 39,271 participants from 19 countries, described in 37 articles were studied. The estimates for the prevalence of circulating T. solium antigens for Africa, Latin America and Asia were: 7.30% (95% CI [4.23-12.31]), 4.08% (95% CI [2.77-5.95]) and 3.98% (95% CI [2.81-5.61]), respectively. Seroprevalence estimates of T. solium antibodies were 17.37% (95% CI [3.33-56.20]), 13.03% (95% CI [9.95-16.88]) and 15.68% (95% CI [10.25-23.24]) respectively. Taeniasis reported prevalences ranged from 0 (95% CI [0.00-1.62]) to 17.25% (95% CI [14.55-20.23]). SIGNIFICANCE: A significant variation in the sero-epidemiological data was observed within each continent, with African countries reporting the highest apparent prevalences of active infections. Intrinsic factors in the human host such as age and immunity were main determinants for the occurrence of infections, while exposure was mostly related to environmental factors which varied from community to community. PMID- 26147944 TI - Neutrophilic leukemoid reaction in multiple myeloma. PMID- 26147945 TI - Heart rate recovery in elite athletes: the impact of age and exercise capacity. AB - There is compelling evidence that postexercise heart rate recovery (HRR) is a valid indicator of sympaticovagal balance. It is also used in prescription and monitoring of athletic training. The purpose of our study was to determine HRR after maximal exercise among elite athletes with respect to age. A total of 274 elite male Caucasian athletes were randomly selected from the larger sample and divided into two groups: adolescent (group Y) and adult athletes (>=18 years; group A). They performed maximal cardiopulmonary exercise testing on a treadmill. Heart rate recovery was calculated as the rate of decline of HR from peak exercise to rates 1, 2 and 3 min after cessation of exercise (HRR1, HRR2 and HRR3). A significantly higher HRR1 was found in group A (29.5 +/- 15.6 versus 22.4 +/- 10.8, P<0.001), but HRR3 was higher in group Y (82.7 +/- 10.2 versus 79.9 +/- 12.25; P = 0.04). Stepwise multivariate linear regression analysis showed that, among all subjects, the HRR1 alone was independently associated with age (P<0.001). The maximal oxygen consumption (VO2 max) was in a negative relationship with HRR1 and in a positive one with HRR3 (P<0.05) with respect to all athletes. The HRR during 3 min postexercise should be reported for the purpose of better assessing functional adaptation to exercise among elite athletes as well as the age-associated differences in recovery. Higher values of HRR1 should be expected in older athletes, and HRR3 could be used as an index of aerobic capacity, irrespective of age. PMID- 26147946 TI - Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age. AB - IMPORTANCE: Individuals in the presymptomatic stage of Alzheimer disease (AD) are increasingly being targeted for AD secondary prevention trials. How early during the normal life span underlying AD pathologies begin to develop, their patterns of change over time, and their relationship with future cognitive decline remain to be determined. OBJECTIVE: To characterize the within-person trajectories of cerebrospinal fluid (CSF) biomarkers of AD over time and their association with changes in brain amyloid deposition and cognitive decline in cognitively normal middle-aged individuals. DESIGN, SETTING, AND PARTICIPANTS: As part of a cohort study, cognitively normal (Clinical Dementia Rating [CDR] of 0) middle-aged research volunteers (n = 169) enrolled in the Adult Children Study at Washington University, St Louis, Missouri, had undergone serial CSF collection and longitudinal clinical assessment (mean, 6 years; range, 0.91-11.3 years) at 3 year intervals at the time of analysis, between January 2003 and November 2013. A subset (n = 74) had also undergone longitudinal amyloid positron emission tomographic imaging with Pittsburgh compound B (PiB) in the same period. Serial CSF samples were analyzed for beta-amyloid 40 (Abeta40), Abeta42, total tau, tau phosphorylated at threonine 181 (P-tau181), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Within-person measures were plotted according to age and AD risk defined by APOE genotype (epsilon4 carriers vs noncarriers). Linear mixed models were used to compare estimated biomarker slopes among middle-age bins at baseline (early, 45-54 years; mid, 55-64 years; late, 65 74 years) and between risk groups. Within-person changes in CSF biomarkers were also compared with changes in cortical PiB binding and progression to a CDR higher than 0 at follow-up. MAIN OUTCOMES AND MEASURES: Changes in Abeta40, Abeta42, total tau, P-tau181, VILIP-1, and YKL-40 and, in a subset of participants, changes in cortical PiB binding. RESULTS: While there were no consistent longitudinal patterns in Abeta40 (P = .001-.97), longitudinal reductions in Abeta42 were observed in some individuals as early as early middle age (P <= .05) and low Abeta42 levels were associated with the development of cortical PiB-positive amyloid plaques (area under receiver operating characteristic curve = 0.9352; 95% CI, 0.8895-0.9808), especially in mid middle age (P < .001). Markers of neuronal injury (total tau, P-tau181, and VILIP-1) dramatically increased in some individuals in mid and late middle age (P <= .02), whereas the neuroinflammation marker YKL-40 increased consistently throughout middle age (P <= .003). These patterns were more apparent in at-risk epsilon4 carriers (Abeta42 in an allele dose-dependent manner) and appeared to be associated with future cognitive deficits as determined by CDR. CONCLUSIONS AND RELEVANCE: Longitudinal CSF biomarker patterns consistent with AD are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline. Such measures may be useful for targeting middle-aged, asymptomatic individuals for therapeutic trials designed to prevent cognitive decline. PMID- 26147947 TI - Pharmacological Targeting of Protease-Activated Receptor 2 Affords Protection from Bleomycin-Induced Pulmonary Fibrosis. AB - Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease that remains refractory to therapy. Despite increasing evidence that protease-activated receptor 2 (PAR-2) contributes to fibrosis, its importance in pulmonary fibrosis is under debate. We addressed whether PAR-2 deficiency persistently reduces bleomycin-induced pulmonary fibrosis or merely delays disease progression and whether pharmacological PAR-2 inhibition limits experimental pulmonary fibrosis. Bleomycin was instilled intranasally into wild type or PAR-2-deficient mice in the presence/absence of a specific PAR-2 antagonist (P2pal-18S). Pulmonary fibrosis was consistently reduced in PAR-2 deficient mice throughout the fibrotic phase, as evident from reduced Ashcroft scores (29%) and hydroxyproline levels (26%) at d 28. Moreover, P2pal-18S inhibited PAR-2-induced profibrotic responses in both murine and primary human pulmonary fibroblasts (p < 0.05). Once daily treatment with P2pal-18S reduced the severity and extent of fibrotic lesions in lungs of bleomycin-treated wild-type mice but did not further reduce fibrosis in PAR-2-deficient mice. Importantly, P2pal-18S treatment starting even 7 d after the onset of fibrosis limits pulmonary fibrosis as effectively as when treatment was started together with bleomycin instillation. Overall, PAR-2 contributes to the progression of pulmonary fibrosis, and targeting PAR-2 may be a promising therapeutic strategy for treating pulmonary fibrosis. PMID- 26147949 TI - Direct Observation of Transient Surface Species during Ge Nanowire Growth and Their Influence on Growth Stability. AB - Surface adsorbates are well-established choreographers of material synthesis, but the presence and impact of these short-lived species on semiconductor nanowire growth are largely unknown. Here, we use infrared spectroscopy to directly observe surface adsorbates, hydrogen atoms and methyl groups, chemisorbed to the nanowire sidewall and show they are essential for the stable growth of Ge nanowires via the vapor-liquid-solid mechanism. We quantitatively determine the surface coverage of hydrogen atoms during nanowire growth by comparing nu(Ge-H) absorption bands from operando measurements (i.e., during growth) to those after saturating the nanowire sidewall with hydrogen atoms. This method provides sub monolayer chemical information at relevant reaction conditions while accounting for the heterogeneity of sidewall surface sites and their evolution during elongation. Our findings demonstrate that changes to surface bonding are critical to understand Ge nanowire synthesis and provide new guidelines for rationally selecting catalysts, forming heterostructures, and controlling dopant profiles. PMID- 26147948 TI - Data Gathering Bias: Trait Vulnerability to Psychotic Symptoms? AB - BACKGROUND: Jumping to conclusions (JTC) is associated with psychotic disorder and psychotic symptoms. If JTC represents a trait, the rate should be (i) increased in people with elevated levels of psychosis proneness such as individuals diagnosed with borderline personality disorder (BPD), and (ii) show a degree of stability over time. METHODS: The JTC rate was examined in 3 groups: patients with first episode psychosis (FEP), BPD patients and controls, using the Beads Task. PANSS, SIS-R and CAPE scales were used to assess positive psychotic symptoms. Four WAIS III subtests were used to assess IQ. RESULTS: A total of 61 FEP, 26 BPD and 150 controls were evaluated. 29 FEP were revaluated after one year. 44% of FEP (OR = 8.4, 95% CI: 3.9-17.9) displayed a JTC reasoning bias versus 19% of BPD (OR = 2.5, 95% CI: 0.8-7.8) and 9% of controls. JTC was not associated with level of psychotic symptoms or specifically delusionality across the different groups. Differences between FEP and controls were independent of sex, educational level, cannabis use and IQ. After one year, 47.8% of FEP with JTC at baseline again displayed JTC. CONCLUSIONS: JTC in part reflects trait vulnerability to develop disorders with expression of psychotic symptoms. PMID- 26147950 TI - From the morphological to the transcriptomic characterization of a compromised three-dimensional in vitro model mimicking atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which skin barrier function is disrupted. In this AD environment, proinflammatory cytokines are upregulated, promoting a vicious circle of inflammation. Although several three-dimensional in vitro models mimicking AD have been published, no study has presented a fully characterized and controlled model of AD-related inflammation. OBJECTIVES: To develop and characterize, from the morphological to the molecular level, a compromised reconstructed epidermis (RE) mimicking AD related inflammation in vitro. METHODS: Normal human keratinocytes were used to generate RE, treated or not with an inflammatory cocktail (polyinosinic polycytidylic acid, tumour necrosis factor-alpha, interleukin-4 and interleukin 13). RESULTS: The inflammatory cocktail induces some modifications observed in patients with AD: (i) it leads to spongiosis; (ii) it alters early and terminal differentiation proteins; (iii) it increases thymic stromal lymphopoietin and interleukin-8 secretion by keratinocytes and (iv) it results in a specific gene expression pattern. CONCLUSIONS: The inflammatory context contributes to the morphological, functional and transcriptomic changes observed in AD skin. As a result, this compromised RE model shares some characteristics with those found in AD skin and thus can be used as a relevant tool for screening formulations and drugs for the treatment of AD. PMID- 26147951 TI - Concentrations of Persistent Organic Pollutants in California Children's Whole Blood and Residential Dust. AB - We evaluated relationships between persistent organic pollutant (POP) levels in the blood of children with leukemia and POP levels in dust from their household vacuum cleaners. Blood and dust were collected from participants of the California Childhood Leukemia Study at various intervals from 1999 to 2007 and analyzed for two polybrominated diphenyl ethers (PBDEs), two polychlorinated biphenyls (PCBs), and two organochlorine pesticides using gas chromatography-mass spectrometry. Due to small blood sample volumes (100 MUL), dichlorodiphenyldichloroethylene (DDE) and BDE-153 were the only analytes with detection frequencies above 70%. For each analyte, depending on its detection frequency, a multivariable linear or logistic regression model was used to evaluate the relationship between POP levels in blood and dust, adjusting for child's age, ethnicity, and breastfeeding duration; mother's country of origin; household annual income; and blood sampling date. In linear regression, concentrations of BDE-153 in blood and dust were positively associated; whereas, DDE concentrations in blood were positively associated with breastfeeding, maternal birth outside the U.S., and Hispanic ethnicity, but not with corresponding dust-DDE concentrations. The probability of PCB-153 detection in a child's blood was marginally associated with dust-PCB-153 concentrations (p = 0.08) in logistic regression and significantly associated with breastfeeding. Our findings suggest that dust ingestion is a source of children's exposure to certain POPs. PMID- 26147952 TI - One-Pot Chemoenzymatic Cascade for Labeling of the Epigenetic Marker 5 Hydroxymethylcytosine. AB - The epigenetic DNA modification 5-hydroxymethylcytosine (5-hmC) is important for the regulation of gene expression during development and in tumorigenesis. 5-hmC can be selectively glycosylated by T4 beta-glucosyltransferase (beta-GT); introduction of an azide on the attached sugar provides a chemical handle for isolation or fluorescent tagging of 5-hmC residues by click chemistry. This approach has not been broadly adopted because of the challenging synthesis and limited commercial availability of the glycosylation substrate, 6-deoxy-6-azido alpha-D-glucopyranoside. We report the enzyme-assisted synthesis of this precursor by the uridylyltransferase from Pasteurella multocida (PmGlmU). We were able to directly label 5-hmC in genomic DNA by an enzymatic cascade involving successive action of PmGlmU and beta-GT. This is a facile and cost-effective one pot chemoenzymatic methodology for 5-hmC analysis. PMID- 26147953 TI - In Situ Study of Lithiation and Delithiation of MoS2 Nanosheets Using Electrochemical Liquid Cell Transmission Electron Microscopy. AB - We report the observation of lithiation/delithiation of MoS2 nanosheets in a LiPF6/EC/DEC commercial electrolyte for the application of lithium-ion batteries using electrochemical liquid cell transmission electron microscopy (TEM). Upon discharge in a voltage range of 1.8-1.2 V, MoS2 on the Ti electrode underwent irreversible decomposition resulting in fragmentation of the MoS2 nanosheets into 5-10 nm MoS2 nanoparticles. Repeated experiments also show that some MoS2 nanosheets do not decompose upon lithiation. Instead, lithiation induced structural expansion and deformation has been observed. A solid-electrolyte interface (SEI) was formed on the anode side of the Ti electrode in contact with Li metal. The SEI layer is composed of LiF nanocrystals distributed within the entire layer with the constituent elements C, O, and F. However, no passivation film was observed on the cathode side of the Ti electrode with MoS2 nanosheets on it. Such an in situ electrochemical liquid cell TEM study sheds light on battery degradation mechanisms. PMID- 26147955 TI - Tracheal diverticulum with decompensation after 8 years of conservative therapy requiring surgical solution. AB - Tracheal diverticulum is a benign cystic mass in the cervical and mediastinal regions, with an incidence of 1% in post-mortem findings, and 2% in CT findings. The lesion is in most cases completely asymptomatic and is most commonly incidentally detected during a CT examination. We present the case of a young female patient with a tracheal diverticulum who has been followed up for 8 years by pediatric pneumologist. Patient health state deteriorated and she developed stress-induced dyspnea requiring surgical resection. Moreover, we mention differential diagnosis of other mediastinal cystic lesions. PMID- 26147954 TI - Impact of Preoperative Anaemia and Blood Transfusion on Postoperative Outcomes in Gynaecological Surgery. AB - OBJECTIVE: To evaluate the effect of preoperative anaemia and blood transfusion on 30-day postoperative morbidity and mortality in patients undergoing gynecological surgery. STUDY DESIGN: Data were analyzed from 12,836 women undergoing operation in the American College of Surgeons National Surgical Quality Improvement Program. Outcomes measured were; 30-day postoperative mortality, composite and specific morbidities (cardiac, respiratory, central nervous system, renal, wound, sepsis, venous thrombosis, or major bleeding). Multivariate logistic regression models were performed using adjusted odds ratios (ORadj) to assess the independent effects of preoperative anaemia (hematocrit <36.0%) on outcomes, effect estimates were performed before and after adjustment for perioperative transfusion requirement. RESULTS: The prevalence of preoperative anaemia was 23.9% (95%CI: 23.2-24.7). Adjusted for confounders by multivariate logistic regression; preoperative anaemia was independently and significantly associated with increased odds of 30-day mortality (OR: 2.40, 95%CI: 1.06-5.44) and composite morbidity (OR: 1.80, 95%CI: 1.45-2.24). This was reflected by significantly higher adjusted odds of almost all specific morbidities including; respiratory, central nervous system, renal, wound, sepsis, and venous thrombosis. Blood Transfusion increased the effect of preoperative anaemia on outcomes (61% of the effect on mortality and 16% of the composite morbidity). CONCLUSIONS: Preoperative anaemia is associated with adverse post operative outcomes in women undergoing gynecological surgery. This risk associated with preoperative anaemia did not appear to be corrected by use of perioperative transfusion. PMID- 26147957 TI - Epidural Hematoma Complication after Rapid Chronic Subdural Hematoma Evacuation: A Case Report. AB - BACKGROUND: Chronic subdural hematoma generally occurs in the elderly. After chronic subdural hematoma evacuation surgery, the development of epidural hematoma is a very rare entity. CASE REPORT: We report the case of a 41-year-old man with an epidural hematoma complication after chronic subdural hematoma evacuation. Under general anesthesia, the patient underwent a large craniotomy with closed system drainage performed to treat the chronic subdural hematoma. After chronic subdural hematoma evacuation, there was epidural leakage on the following day. CONCLUSIONS: Although trauma is the most common risk factor in young CSDH patients, some other predisposing factors may exist. Intracranial hypotension can cause EDH. Craniotomy and drainage surgery can usually resolve the problem. Because of rapid dynamic intracranial changes, epidural leakages can occur. A large craniotomy flap and silicone drainage in the operation area are key safety points for neurosurgeons and hydration is essential. PMID- 26147956 TI - Identification of Salmonella Typhimurium Deubiquitinase SseL Substrates by Immunoaffinity Enrichment and Quantitative Proteomic Analysis. AB - Ubiquitination is a key protein post-translational modification that regulates many important cellular pathways and whose levels are regulated by equilibrium between the activities of ubiquitin ligases and deubiquitinases. Here, we present a method to identify specific deubiquitinase substrates based on treatment of cell lysates with recombinant enzymes, immunoaffinity purification, and global quantitative proteomic analysis. As a model system to identify substrates, we used a virulence-related deubiquitinase, SseL, secreted by Salmonella enterica serovar Typhimurium into host cells. Using this approach, two SseL substrates were identified in the RAW 264.7 murine macrophage-like cell line, S100A6 and heterogeneous nuclear ribonuclear protein K, in addition to the previously reported K63-linked ubiquitin chains. These substrates were further validated by a combination of enzymatic and binding assays. This method can be used for the systematic identification of substrates of deubiquitinases from other organisms and applied to study their functions in physiology and disease. PMID- 26147958 TI - Pharmacological interventions for self-harm in adults. AB - BACKGROUND: Self-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and strongly associated with suicide. This is an update of a broader Cochrane review on psychosocial and pharmacological treatments for deliberate SH, first published in 1998 and previously updated in 1999. We have now divided the review into three separate reviews. This review is focused on pharmacological interventions in adults who self harm. OBJECTIVES: To identify all randomised controlled trials of pharmacological agents or natural products for SH in adults, and to conduct meta-analyses (where possible) to compare the effects of specific treatments with comparison types of treatment (e.g., placebo/alternative pharmacological treatment) for SH patients. SEARCH METHODS: For this update the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) Trials Search Co-ordinator searched the CCDAN Specialised Register (September 2014). Additional searches of MEDLINE, EMBASE, PsycINFO, and CENTRAL were conducted to October 2013. SELECTION CRITERIA: We included randomised controlled trials comparing pharmacological treatments or natural products with placebo/alternative pharmacological treatment in individuals with a recent (within six months) episode of SH resulting in presentation to clinical services. DATA COLLECTION AND ANALYSIS: We independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and 95% CI. Meta-analysis was only possible for one intervention (i.e. newer generation antidepressants) on repetition of SH at last follow-up. For this analysis, we pooled data using a random-effects model. The overall quality of evidence for the primary outcome was appraised for each intervention using the GRADE approach. MAIN RESULTS: We included seven trials with a total of 546 patients. The largest trial included 167 participants. We found no significant treatment effect on repetition of SH for newer generation antidepressants (n = 243; k = 3; OR 0.76, 95% CI 0.42 to 1.36; GRADE: low quality of evidence), low-dose fluphenazine (n = 53; k = 1; OR 1.51, 95% CI 0.50 to 4.58; GRADE: very low quality of evidence), mood stabilisers (n = 167; k = 1; OR 0.99, 95% CI 0.33 to 2.95; GRADE: low quality of evidence), or natural products (n = 49; k = 1; OR 1.33, 95% CI 0.38 to 4.62; GRADE: low quality of evidence). A significant reduction in SH repetition was found in a single trial of the antipsychotic flupenthixol (n = 30; k = 1; OR 0.09, 95% CI 0.02 to 0.50), although the quality of evidence for this trial, according to the GRADE criteria, was very low. No data on adverse effects, other than the planned outcomes relating to suicidal behaviour, were reported. AUTHORS' CONCLUSIONS: Given the low or very low quality of the available evidence, and the small number of trials identified, it is not possible to make firm conclusions regarding pharmacological interventions in SH patients. More and larger trials of pharmacotherapy are required. In view of an indication of positive benefit for flupenthixol in an early small trial of low quality, these might include evaluation of newer atypical antipsychotics. Further work should include evaluation of adverse effects of pharmacological agents. Other research could include evaluation of combined pharmacotherapy and psychological treatment. PMID- 26147959 TI - Male-Specific Alleviation of Iron-Induced Striatal Injury by Inhibition of Autophagy. AB - Men exhibit a worse survival rate than premenopausal women after intracerebral hemorrhage (ICH), however, no sex-specific management has been concerned. In a rat model involving infusion of ferrous citrate (FC) that simulates iron accumulation after hemorrhage, a higher degree of autophagy associated with higher injury severity was observed in striatum of males than in females. Since the imbalance between the levels of autophagy and energy demand may lead to cell death, we proposed that FC-induced autophagy is detrimental in a male specific manner and autophagy modulation affects injury severity in a sex-dependent manner. Rapamycin, an autophagy inducer, and conditional knockout gene of autophagy-related protein 7 (Atg7) in dopamine receptor D2 (DRD2) neurons were used to test our hypothesis using a mouse model with striatal FC infusion. The result showed that the levels of autophagic cell death and injury severity were higher in male than in female mice. Pre-treatment of FC-infused females with rapamycin increased the FC-induced behavioral deficit and DRD2 neuron death. However, DRD2 neuron-specific knockout of Atg7 decreased FC-induced injury severity and the number of TUNEL(+) DRD2 neurons in males. These results suggest that autophagy in FC-infusion males is overactive with maladaptive consequences and inhibition of autophagy decreases the severity of FC-induced striatal injury in males. These findings present prospects for male-specific therapeutic strategy that targets autophagy in patients suffering from iron overload. PMID- 26147960 TI - Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease. AB - INTRODUCTION: Vascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho. METHODS AND MATERIAL: In 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively. RESULTS: fT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness. DISCUSSION: The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail. PMID- 26147961 TI - Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure. AB - INTRODUCTION: Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. METHODS: 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. RESULTS: More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. CONCLUSIONS: In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity. PMID- 26147962 TI - Prevalence of alcohol-impaired driving and riding in northern Ghana. AB - OBJECTIVE: The objective of this study was to determine the roadside prevalence of alcohol-impaired driving among drivers and riders in northern Ghana. The study also verifies motorists' perceptions of their own alcohol use and knowledge of the legal blood alcohol concentration (BAC) limit in Ghana. METHOD: With the assistance of police, systematic random sampling was used to collect data at roadblocks using a cross-sectional study design. Breathalyzers were used to screen whether motorists had detectable alcohol in their breath and follow-up breath tests were conducted to measure the actual breath alcohol levels among positive participants. RESULTS: In all, 9.7% of the 789 participants had detectable alcohol, among whom 6% exceeded the legal BAC limit of 0.08%. The prevalence of alcohol-impaired driving/riding was highest among cyclists (10% of all cyclists breath-tested) followed by truck drivers (9%) and motorcyclists (7% of all motorcyclists breath-tested). The occurrence of a positive BAC among cyclists was about 8 times higher (odds ratio [OR] = 7.73; P < .001) and it was 2 times higher among motorcyclists (OR = 2.30; P = .039) compared to private car drivers. The likelihood for detecting a positive BAC among male motorists/riders was higher than that among females (OR = 1.67; P = .354). The odds for detecting a positive BAC among weekend motorists/riders was significantly higher than on weekdays (OR = 2.62; P = .001). CONCLUSION: Alcohol-impaired driving/riding in Ghana is high by international standards. In order to attenuate the harmful effects of alcohol misuse such as alcohol-impaired driving/riding, there is the need to educate road users about how much alcohol they can consume and stay below the legal limit. The police should also initiate random breath testing to instill the deterrence of detection, certainty of apprehension and punishment, and severity and celerity of punishment among drink-driving motorists and riders. PMID- 26147963 TI - Incidence and Geographic Distribution of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal Province, South Africa. AB - South Africa is experiencing a widespread drug-resistant tuberculosis epidemic, although data are limited regarding the current situation. This study finds that the extensively drug-resistant tuberculosis (XDR-TB) incidence in KwaZulu-Natal increased to 3.5 cases/100,000 (776 cases) in 2011-2012. XDR-TB cases are widely distributed geographically, with the majority of districts experiencing a rise in incidence. PMID- 26147964 TI - Century-Long Warming Trends in the Upper Water Column of Lake Tanganyika. AB - Lake Tanganyika, the deepest and most voluminous lake in Africa, has warmed over the last century in response to climate change. Separate analyses of surface warming rates estimated from in situ instruments, satellites, and a paleolimnological temperature proxy (TEX86) disagree, leaving uncertainty about the thermal sensitivity of Lake Tanganyika to climate change. Here, we use a comprehensive database of in situ temperature data from the top 100 meters of the water column that span the lake's seasonal range and lateral extent to demonstrate that long-term temperature trends in Lake Tanganyika depend strongly on depth, season, and latitude. The observed spatiotemporal variation in surface warming rates accounts for small differences between warming rate estimates from in situ instruments and satellite data. However, after accounting for spatiotemporal variation in temperature and warming rates, the TEX86 paleolimnological proxy yields lower surface temperatures (1.46 degrees C lower on average) and faster warming rates (by a factor of three) than in situ measurements. Based on the ecology of Thaumarchaeota (the microbes whose biomolecules are involved with generating the TEX86 proxy), we offer a reinterpretation of the TEX86 data from Lake Tanganyika as the temperature of the low-oxygen zone, rather than of the lake surface temperature as has been suggested previously. Our analyses provide a thorough accounting of spatiotemporal variation in warming rates, offering strong evidence that thermal and ecological shifts observed in this massive tropical lake over the last century are robust and in step with global climate change. PMID- 26147965 TI - What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries. AB - BACKGROUND: In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts. METHODS AND FINDINGS: Methods. Design: Epidemiological study using a combination of self report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male) and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male). Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU funded "OSPI-Europe"-project (www.ospi-europe.com). We calculated method-specific lethality using the number of completed suicides per method * 100 / (number of completed suicides per method + number of attempted suicides per method). We tested gender differences in the distribution of suicidal acts for significance by using the chi2-test for two-by-two tables. We assessed the effect sizes with phi coefficients (phi). We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts. FINDINGS MAIN RESULTS: Suicidal acts (fatal and non-fatal) were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts) versus 4.05% (regarding 4836 suicidal acts)), the difference being significant for the methods hanging, jumping, moving objects, sharp objects and poisoning by substances other than drugs. Median age at time of suicidal behaviour (35-44 years) did not differ between males and females. The overall gender difference in lethality of suicidal behaviour was explained by males choosing more lethal suicide methods (odds ratio (OR) = 2.03; 95% CI = 1.65 to 2.50; p < 0.000001) and additionally, but to a lesser degree, by a higher lethality of suicidal acts for males even within the same method (OR = 1.64; 95% CI = 1.32 to 2.02; p = 0.000005). Results of a regression analysis revealed neither age nor country differences were significant predictors for gender differences in the lethality of suicidal acts. The proportion of serious suicide attempts among all non-fatal suicidal acts with known intentionality (NFSAi) was significantly higher in men (57.1%; 1,207 of 2,115 NFSAi) than in women (48.6%; 1,508 of 3,100 NFSAi) (chi2 = 35.74; p < 0.000001). MAIN LIMITATIONS OF THE STUDY: Due to restrictive data security regulations to ensure anonymity in Ireland, specific ages could not be provided because of the relatively low absolute numbers of suicide in the Irish intervention and control region. Therefore, analyses of the interaction between gender and age could only be conducted for three of the four countries. Attempted suicides were assessed for patients presenting to emergency departments or treated in hospitals. An unknown rate of attempted suicides remained undetected. This may have caused an overestimation of the lethality of certain methods. Moreover, the detection of attempted suicides and the registration of completed suicides might have differed across the four countries. Some suicides might be hidden and misclassified as undetermined deaths. CONCLUSIONS: Men more often used highly lethal methods in suicidal behaviour, but there was also a higher method specific lethality which together explained the large gender differences in the lethality of suicidal acts. Gender differences in the lethality of suicidal acts were fairly consistent across all four European countries examined. Males and females did not differ in age at time of suicidal behaviour. Suicide attempts by males were rated as being more serious independent of the method used, with the exceptions of attempted hanging, suggesting gender differences in intentionality associated with suicidal behaviour. These findings contribute to understanding of the spectrum of reasons for gender differences in the lethality of suicidal behaviour and should inform the development of gender specific strategies for suicide prevention. PMID- 26147966 TI - Potential of Wood-Rotting Fungi to Attack Polystyrene Sulfonate and Its Depolymerisation by Gloeophyllum trabeum via Hydroquinone-Driven Fenton Chemistry. AB - Synthetic polymers often pose environmental hazards due to low biodegradation rates and resulting accumulation. In this study, a selection of wood-rotting fungi representing different lignocellulose decay types was screened for oxidative biodegradation of the polymer polystyrene sulfonate (PSS). Brown-rot basidiomycetes showed PSS depolymerisation of up to 50 % reduction in number average molecular mass (Mn) within 20 days. In-depth investigations with the most efficient depolymeriser, a Gloeophyllum trabeum strain, pointed at extracellular hydroquinone-driven Fenton chemistry responsible for depolymerisation. Detection of hydroxyl radicals present in the culture supernatants showed good compliance with depolymerisation over the time course of PSS degradation. 2,5-Dimethoxy-1,4 hydroquinone (2,5-DMHQ), which was detected in supernatants of active cultures via liquid chromatography and mass spectrometry, was demonstrated to drive the Fenton processes in G. trabeum cultures. Up to 80% reduction in Mn of PSS where observed when fungal cultures were additionally supplemented with 2,5-dimethoxy benzoquinone, the oxidized from of 2,5-DMHQ. Furthermore, 2,5-DMHQ could initiate the Fenton's reagent-mediated PSS depolymerisation in cell-free systems. In contrast, white-rot fungi were unable to cause substantial depolymerising effects despite the expression of lignin-modifying exo-enzymes. Detailed investigations with laccase from Trametes versicolor revealed that only in presence of certain redox mediators limited PSS depolymerisation occurred. Our results indicate that brown-rot fungi might be suitable organisms for the biodegradation of recalcitrant synthetic polymeric pollutants. PMID- 26147967 TI - Morphogenetic Implications of Peristalsis-Driven Fluid Flow in the Embryonic Lung. AB - Epithelial organs are almost universally secretory. The lung secretes mucus of extremely variable consistency. In the early prenatal period, the secretions are of largely unknown composition, consistency, and flow rates. In addition to net outflow from secretion, the embryonic lung exhibits transient reversing flows from peristalsis. Airway peristalsis (AP) begins as soon as the smooth muscle forms, and persists until birth. Since the prenatal lung is liquid-filled, smooth muscle action can transport fluid far from the immediately adjacent tissues. The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens. We hypothesize that these effects play an important role in lung morphogenesis. To test these hypotheses in a quantitative framework, we analyzed the fluid-structure interactions between embryonic tissues and lumen fluid resulting from peristaltic waves that partially occlude the airway. We found that if the airway is closed, fluid transport is minimal; by contrast, if the trachea is open, shear rates can be very high, particularly at the stenosis. We performed a parametric analysis of flow characteristics' dependence on tissue stiffnesses, smooth muscle force, geometry, and fluid viscosity, and found that most of these relationships are governed by simple ratios. We measured the viscosity of prenatal lung fluid with passive bead microrheology. This paper reports the first measurements of the viscosity of embryonic lung lumen fluid. In the range tested, lumen fluid can be considered Newtonian, with a viscosity of 0.016 +/- 0.008 Pa-s. We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens. These effects may be the intermediate mechanisms for the enhancement of branching seen in occluded embryonic lungs. PMID- 26147968 TI - Plasmid-Encoded RepA Proteins Specifically Autorepress Individual repABC Operons in the Multipartite Rhizobium leguminosarum bv. trifolii Genome. AB - Rhizobia commonly have very complex genomes with a chromosome and several large plasmids that possess genes belonging to the repABC family. RepA and RepB are members of the ParA and ParB families of partitioning proteins, respectively, whereas RepC is crucial for plasmid replication. In the repABC replicons, partitioning and replication functions are transcriptionally linked resulting in complex regulation of rep gene expression. The genome of R. leguminosarum bv. trifolii TA1 (RtTA1) consists of a chromosome and four plasmids (pRleTA1a-d), equipped with functional repABC genes. In this work, the regulation of transcription of the individual repABC cassettes of the four RtTA1 plasmids was studied. The involvement of the RepA and RepB as well as parS-like centromere sites in this process was depicted, demonstrating some dissimilarity in expression of respective rep regions. RtTA1 repABC genes of individual plasmids formed operons, which were negatively regulated by RepA and RepB. Individual RepA were able to bind to DNA without added nucleotides, but in the presence of ADP, bound specifically to their own operator sequences containing imperfect palindromes, and caused operon autorepression, whereas the addition of ATP stimulated non-specific binding of RepA to DNA. The RepA proteins were able to dimerize/oligomerize: in general dimers formed independently of ATP or ADP, although ATP diminished the concentration of oligomers that were produced. By the comprehensive approach focusing on a set of plasmids instead of individual replicons, the work highlighted subtle differences between the organization and regulation of particular rep operons as well as the structures and specificity of RepA proteins, which contribute to the fine-tuned coexistence of several replicons with similar repABC cassettes in the complex bacterial genome. PMID- 26147970 TI - The Macrophage Galactose-Type C-Type Lectin (MGL) Modulates Regulatory T Cell Functions. AB - Regulatory T cells (Tregs) are physiologically designed to prevent autoimmune disease and maintain self-tolerance. In tumour microenvironments, their presence is related to a poor prognosis, and they influence the therapeutic outcome due to their capacity to suppress the immune response by cell-cell contact and to release immunosuppressive cytokines. In this study, we demonstrate that Treg immunosuppressive activity can be modulated by the cross-linking between the CD45RA expressed by Tregs and the C-type lectin MGL. This specific interaction strongly decreases the immunosuppressive activity of Tregs, restoring the proliferative capacity of co-cultured T lymphocytes. This effect can be attributed to changes in CD45RA and TCR signalling through the inhibition of Lck and inactivation of Zap-70, an increase in the Foxp3 methylation status and, ultimately, the reduced production of suppressive cytokines. These results indicate a role of MGL as an immunomodulator within the tumour microenvironment interfering with Treg functions, suggesting its possible use in the design of anticancer vaccines. PMID- 26147969 TI - Alkbh8 Regulates Selenocysteine-Protein Expression to Protect against Reactive Oxygen Species Damage. AB - Environmental and metabolic sources of reactive oxygen species (ROS) can damage DNA, proteins and lipids to promote disease. Regulation of gene expression can prevent this damage and can include increased transcription, translation and post translational modification. Cellular responses to ROS play important roles in disease prevention, with deficiencies linked to cancer, neurodegeneration and ageing. Here we detail basal and damage-induced translational regulation of a group of oxidative-stress response enzymes by the tRNA methyltransferase Alkbh8. Using a new gene targeted knockout mouse cell system, we show that Alkbh8-/- embryonic fibroblasts (MEFs) display elevated ROS levels, increased DNA and lipid damage and hallmarks of cellular stress. We demonstrate that Alkbh8 is induced in response to ROS and is required for the efficient expression of selenocysteine containing ROS detoxification enzymes belonging to the glutathione peroxidase (Gpx1, Gpx3, Gpx6 and likely Gpx4) and thioredoxin reductase (TrxR1) families. We also show that, in response to oxidative stress, the tRNA modification 5 methoxycarbonylmethyl-2'-O-methyluridine (mcm5Um) increases in normal MEFs to drive the expression of ROS detoxification enzymes, with this damage-induced reprogramming of tRNA and stop-codon recoding corrupted in Alkbh8-/- MEFS. These studies define Alkbh8 and tRNA modifications as central regulators of cellular oxidative stress responses in mammalian systems. In addition they highlight a new animal model for use in environmental and cancer studies and link translational regulation to the prevention of DNA and lipid damage. PMID- 26147971 TI - Comparative Metabolomic Analysis of the Neuroprotective Effects of Scutellarin and Scutellarein against Ischemic Insult. AB - For more than thirty years, scutellarin (Scu) has been used in China to clinically treat acute cerebral infarction and paralysis. Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu. To explore the neuroprotective role of these compounds, we performed ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF/MS) coupled with a pattern recognition approach to investigate metabolomic differences in a rat model of ischemia after treatment with each compound. We examined metabolites in urine, hippocampal tissue, and plasma, and we tentatively identified 23 endogenous metabolites whose levels differed significantly between sham-operated and model groups. Upon pathway analysis, we found an additional 11 metabolic pathways in urine, 14 metabolic pathways in the hippocampal tissue, and 3 metabolic pathways in plasma. These endogenous metabolites were mainly involved in sphingolipid metabolism, lysine biosynthesis, and alanine, aspartate, and glutamate metabolism. We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu. These results demonstrate that Scue is a potential drug for treatment of ischemic insult. PMID- 26147972 TI - Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury. AB - Acute lung injury (ALI) is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV) using low tidal volumes (LVT) plus moderate to high levels of positive end-expiratory pressure (PEEP). However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg) plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg) plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The 'response to microorganisms' was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the 'neuron projection morphogenesis' process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir 27a, Mir-103, Mir-17-5p and Mir-130a) were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated). Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection morphogenesis', which have been never anticipated in ALI pathogenesis, promotes lung-protective effects of LVT with high levels of PEEP. PMID- 26147973 TI - Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment. AB - BACKGROUND: The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored. METHODOLOGY/PRINCIPAL FINDINGS: Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni infected Ugandan males before and after praziquantel treatment. While pre treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1. CONCLUSIONS/SIGNIFICANCE: Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities. PMID- 26147974 TI - Seasonal Dynamics of Soil Microbial Biomass C and N along an Elevational Gradient on the Eastern Tibetan Plateau, China. AB - Little information is available on the seasonal response of soil microbial biomass to climate warming even though it is very sensitive to climate change. A two-year field experiment was conducted in the subalpine and alpine forests of the eastern Tibetan Plateau, China. The intact soil cores from 3,600 m site were incubated in three elevations (3,000 m, 3,300 m and 3,600 m) to simulate climate warming. Soil microbial biomass carbon (MBC) and nitrogen (MBN) were measured at different periods (early growing season [EG], late growing season [LG], onset of soil freezing period [OF], deep soil frozen period [DF] and soil thawing period [ET]) from May 2010 to August 2012. Average air temperature and soil temperature increased with the decrease of elevation during the experimental period. MBC and MBN showed a sharp decrease during the OF and ET in both organic layer and mineral layer at the three sites. Additionally, a relatively high MBC was observed during the DF. MBC and MBN in the soil organic layer decreased with the decrease of elevation but the opposite was true in the mineral soil layer. Warming had stronger effects on soil microbial biomass in the organic layer than in the mineral soil layer. The results indicated that future warming would alter soil microbial biomass and biogeochemical cycling in the forest ecosystems on the eastern Tibetan Plateau. PMID- 26147976 TI - Management of benign biliary strictures: current status and perspective. AB - Benign biliary strictures are common and occur either from hepato-biliary surgery or from diseases including chronic pancreatitis and primary sclerosing cholangitis, among others. The treatment of many such strictures is endoscopic with evolving new approaches especially with fully covered metal stents. The only classification system available is for postoperative strictures with the intention to guide surgical correction. There is no useful classification system to guide both assessment and management of benign biliary strictures. This proposed classification is relevant to patient care in assisting diagnosis and endoscopic management. PMID- 26147977 TI - Recognizing and managing a deteriorating patient: a randomized controlled trial investigating the effectiveness of clinical simulation in improving clinical performance in undergraduate nursing students. AB - AIMS: To report the results of a randomized controlled trial which explored the effectiveness of clinical simulation in improving the clinical performance of recognizing and managing an adult deteriorating patient in hospital. BACKGROUND: There is evidence that final year undergraduate nurses may lack knowledge, clinical skills and situation awareness required to manage a deteriorating patient competently. The effectiveness of clinical simulation as a strategy to teach the skills required to recognize and manage the early signs of deterioration needs to be evaluated. DESIGN: This study was a two centre phase II single, randomized, controlled trial with single blinded assessments. METHOD: Data were collected in July 2013. Ninety-eight first year nursing students were randomized either into a control group, where they received a traditional lecture, or an intervention group where they received simulation. Participants completed a pre- and postintervention objective structured clinical examination. General Perceived Self Efficacy and Self-Reported Competency scores were measured before and after the intervention. Student satisfaction with teaching was also surveyed. RESULTS: The intervention group performed significantly better in the post-objective structured clinical examination. There was no significant difference in the postintervention General Perceived Self Efficacy and Self Reported Competency scores between the control and intervention group. The intervention group was significantly more satisfied with their teaching method. CONCLUSION: Simulation-based education may be an effective educational strategy to teach nurses the skills to effectively recognize and manage a deteriorating patient. PMID- 26147975 TI - Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases. AB - The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs' unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a "water-soluble" amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of beta-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug's therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component. PMID- 26147979 TI - Jointly Learning Multiple Sequential Dynamics for Human Action Recognition. AB - Discovering visual dynamics during human actions is a challenging task for human action recognition. To deal with this problem, we theoretically propose the multi task conditional random fields model and explore its application on human action recognition. For visual representation, we propose the part-induced spatiotemporal action unit sequence to represent each action sample with multiple partwise sequential feature subspaces. For model learning, we propose the multi task conditional random fields (MTCRFs) model to discover the sequence-specific structure and the sequence-shared relationship. Specifically, the multi-chain graph structure and the corresponding probabilistic model are designed to represent the interaction among multiple part-induced action unit sequences. Moreover we propose the model learning and inference methods to discover temporal context within individual action unit sequence and the latent correlation among different body parts. Extensive experiments are implemented to demonstrate the superiority of the proposed method on two popular RGB human action datasets, KTH & TJU, and the depth dataset in MSR Daily Activity 3D. PMID- 26147978 TI - Structure and Assembly of TP901-1 Virion Unveiled by Mutagenesis. AB - Bacteriophages of the Siphoviridae family represent the most abundant viral morphology in the biosphere, yet many molecular aspects of their virion structure, assembly and associated functions remain to be unveiled. In this study, we present a comprehensive mutational and molecular analysis of the temperate Lactococcus lactis-infecting phage TP901-1. Fourteen mutations located within the structural module of TP901-1 were created; twelve mutations were designed to prevent full length translation of putative proteins by non-sense mutations, while two additional mutations caused aberrant protein production. Electron microscopy and Western blot analysis of mutant virion preparations, as well as in vitro assembly of phage mutant combinations, revealed the essential nature of many of the corresponding gene products and provided information on their biological function(s). Based on the information obtained, we propose a functional and assembly model of the TP901-1 Siphoviridae virion. PMID- 26147980 TI - Diagnosis of Morquio Syndrome in Dried Blood Spots Based on a New MRM-MS Assay. AB - BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA; Morquio A disease) is an autosomal recessive disease caused and characterized by a decreased activity of N acetylgalactosamine-6-sulfate sulfatase (GALNS), resulting in accumulation of keratan sulfate and chondroitin-6-sulfate in tissues and secondary organ damage. Recently approved enzyme replacement therapy renders the easy and early identification of MPS IVA of out-most importance. METHODOLOGY: We propose a completely new assay for the stable and reproducible detection of GALNS deficiency in dry blood spots (DBS). For the validation blood samples were taken from 59 healthy individuals and 24 randomly selected genetically confirmed MPS IVA patients. The material extracted from DBS was incubated with a 4 methylumbelliferyl-beta-D-galactopyranoside-6-sulfate as a specific substrate. Final enzymatic product, 4-methylumbelliferone, obtained after adding exogenous beta-galactosidase, was quantified by LC/MRM-MS (liquid-chromatography/multiple reaction-monitoring mass-spectrometry). 4-propyl-5-hydroxy-7-methyl-2h-chromen-2 one was used as internal standard, a compound with a similar molecular structure and fragmentation pattern in negative ion mode as 4-methylumbelliferone. FINDINGS: The enzymatic assay yielded a positive and negative predictive value of 1.0 for genetically confirmed MPS IVA patients (GALNS activity of 0.35 +/- 0.21 MUmol/L/h) and for controls with normal GALNS activity (23.1 +/- 5.3 MUmol/L /h). With present enzymatic conditions, the reaction yield in dried blood spots is at least 20 fold higher than any previously reported data with other assays. INTERPRETATION: The present LC/MRM-MS based assay for MPS IVA diagnosis provides an easy, highly-standardized, accurate and innovative quantification of the enzymatic product in vitro and distinguishes perfectly between MPS IVA affected patients and normal controls. This technique will significantly simplify the early detection of MPS IVA patients. PMID- 26147981 TI - Correction: Identification of Reproduction-Specific Genes Associated with Maturation and Estrogen Exposure in a Marine Bivalve Mytilus edulis. PMID- 26147982 TI - Honey Bees (Apis mellifera, L.) as Active Samplers of Airborne Particulate Matter. AB - Honey bees (Apis mellifera L.) are bioindicators of environmental pollution levels. During their wide-ranging foraging activity, these hymenopterans are exposed to pollutants, thus becoming a useful tool to trace the environmental contaminants as heavy metals, pesticides, radionuclides and volatile organic compounds. In the present work we demonstrate that bees can also be used as active samplers of airborne particulate matter. Worker bees were collected from hives located in a polluted postmining area in South West Sardinia (Italy) that is also exposed to dust emissions from industrial plants. The area is included in an official list of sites of national interest for environmental remediation, and has been characterized for the effects of pollutants on the health of the resident population. The head, wings, hind legs and alimentary canal of the bees were investigated with Scanning Electron Microscopy coupled with X-ray spectroscopy (SEM-EDX). The analyses pointed to specific morphological and chemical features of the particulate, and resulted into the identification of three categories of particles: industry-, postmining-, and soil-derived. With the exception of the gut, all the analyzed body districts displayed inorganic particles, mostly concentrated in specific areas of the body (i.e. along the costal margin of the fore wings, the medial plane of the head, and the inner surface of the hind legs). The role of both past mining activities and the industrial activity close to the study area as sources of the particulate matter is also discussed. We conclude that honey bees are able to collect samples of the main airborne particles emitted from different sources, therefore could be an ideal tool for monitoring such a kind of pollutants. PMID- 26147983 TI - Optic Disc Change during Childhood Myopic Shift: Comparison between Eyes with an Enlarged Cup-To-Disc Ratio and Childhood Glaucoma Compared to Normal Myopic Eyes. AB - BACKGROUND: Progressive disc tilting and the development or enlargement of peripapillary atrophy (PPA) are observed during a myopic shift in children. This could be related to the changes around the optic nerve head during eyeball elongation. If the biomechanical properties at or around the optic nerve head are changed after exposure to elevated intraocular pressure (IOP) in glaucoma eyes, different response of the disc tilting and PPA changes could take place during eyeball elongation by myopic shift. On the basis of this background, the aim of this study was to compare the morphological changes in the optic disc induced by a myopic shift during childhood between normal control eyes, eyes from disc suspects with an enlarged cup-to-disc ratio (CDR), and eyes with childhood glaucoma. METHODS: Total of 82 eyes from 82 subjects younger than 14 years of age were included in the study. Serial disc photographs were classified into one of two groups: eyes with an optic nerve head (ONH) or peripapillary atrophy (PPA) change or without an ONH/PPA change. Using ImageJ software, the outlines of the optic disc and PPA were plotted, and the vertical disc diameter (VDD), horizontal disc diameter (HDD), and maximum PPA width (PPW) were measured. The changes in the ratios of these parameters and the relationships between the degree of myopic shift or the ONH/PPA change were analyzed. RESULTS: Twenty-five eyes with normal optic disc appearance, 36 eyes with enlarged cup-to-disc ratio, and 21 eyes of glaucoma patients were analyzed. The initial intraocular pressure (IOP) at diagnosis was significantly different among the groups (P<0.001). The degree of myopic shift during follow-up period was not significantly different among the groups (P=0.612). However, the changes in the HDD/VDD and PPW/VDD ratios were significantly greater in the disc suspect group and significantly smaller in the glaucoma group. Among the 42 eyes with an ONH/PPA change, 16 (38.1%) were from the normal control group, 24 (57.1%) were from the disc suspect group, and 2 (4.8%) were from the glaucoma group (P < 0.001). CONCLUSIONS AND RELEVANCE: The optic disc change during childhood myopic shift was different in eyes with various conditions. Eyes of childhood glaucoma showed less change in the disc morphology during myopic shift compared to eyes with normal disc or enlarged cup to-disc ratio. PMID- 26147984 TI - The Effect of Catheter Ablation on Left Atrial Size and Function for Patients with Atrial Fibrillation: An Updated Meta-Analysis. AB - BACKGROUND: Catheter ablation (CA) for atrial fibrillation (AF) is now an important therapeutic modality for patients with AF. However, data regarding changes in left atrial (LA) function after CA have indicated conflicting results depending on the AF types, follow-up period, and the analytical imaging tools. The objective of this review was to analyze the effect of CA on the LA size and function for patients with AF. METHODS: We searched for studies regarding LA size and function pre- and post-ablation in PubMed, Embase, the Cochrane Library, and Web of Knowledge through May 2014. LA function was measured by LA ejective fraction (LAEF), LA active ejective fraction (LAAEF), or both. Total and subgroup analyses were implemented using Cochrane Review Manager Version 5.2. Weighted mean differences with 95% confidence intervals were used to express the results of continuous outcomes using fixed or random effect models. I2 was used to calculate heterogeneity. To assess publication bias, Egger's test and Begg's funnel plot were performed using Stata 12.0. RESULTS: Twenty-five studies (2040 enrolled patients) were selected for this meta-analysis. The LA diameter (LAD), maximum LA volume, and minimal LA volume were significantly decreased post ablation, as compared with those at a pre-ablation visit. Compared with the pre ablation outcomes, we found no significant differences in LAEF/LAAEF at a post ablation follow-up. Decreases in LA volume and LAEF remained significant post ablation for paroxysmal AF (PAF); however, the LAEF was insignificant changes in persistent AF (PeAF). Heterogeneity was significant in spite which individual study was excluded. A publication bias was not found. In a meta-regression analysis, we did not find any factor that contributed to the heterogeneity. CONCLUSION: With CA, LA volumes and LAD were decreased significantly in patients with AF; LAEF was not significant changes in patients with PeAF but decreased in those with PAF. PMID- 26147985 TI - Diaphragm Repair with a Novel Cross-Linked Collagen Biomaterial in a Growing Rabbit Model. AB - BACKGROUND: Neonates with congenital diaphragmatic hernia and large defects often require patch closure. Acellular collagen matrices (ACM) have been suggested as an alternative to synthetic durable patches as they are remodeled by the host or could also be used for tissue engineering purposes. MATERIALS AND METHODS: 2.0x1.0 cm diaphragmatic defects were created in 6-weeks old New-Zealand white rabbits. We compared reconstruction with a purpose-designed cross-linked ACM (Matricel) to 4-layer non-cross-linked small intestinal submucosa (SIS) and a 1 layer synthetic Dual Mesh (Gore-Tex). Unoperated animals or animals undergoing primary closure (4/0 polyglecaprone) served as age-matched controls. 60 (n = 25) resp. 90 (n = 17) days later, animals underwent chest x-ray and obduction for gross examination of explants, scoring of adhesion and inflammatory response. Also, uniaxial tensiometry was done, comparing explants to contralateral native diaphragmatic tissue. RESULTS: Overall weight nearly doubled from 1,554+/-242 g at surgery to 2,837+/-265 g at obduction (+84%). X-rays did show rare elevation of the left diaphragm (SIS = 1, Gore-Tex = 1, unoperated control = 1), but no herniation of abdominal organs. 56% of SIS and 10% of Matricel patches degraded with visceral bulging in four (SIS = 3, Matricel = 1). Adhesion scores were limited: 0.5 (Matricel) to 1 (SIS, Gore-Tex) to the left lung (p = 0.008) and 2.5 (Gore-Tex), 3 (SIS) and 4 (Matricel) to the liver (p<0.0001). Tensiometry revealed a reduced bursting strength but normal compliance for SIS. Compliance was reduced in Matricel and Gore-Tex (p<0.01). Inflammatory response was characterized by a more polymorphonuclear cell (SIS) resp. macrophage (Matricel) type of infiltrate (p<0.05). Fibrosis was similar for all groups, except there was less mature collagen deposited to Gore-Tex implants (p<0.05). CONCLUSIONS: Matricel induced a macrophage-dominated inflammatory response, more adhesions, had appropriate strength but a lesser compliance compared to native tissue. The herein investigated ACM is not a viable option for CDH repair. PMID- 26147986 TI - Population-based study for human papillomavirus (HPV) infection in young women in Japan: A multicenter study by the Japanese human papillomavirus disease education research survey group (J-HERS). AB - A multi-center study was conducted to examine 6,628 eligible Japanese women aged from 16 to 50 years for uterine cervical abnormality and HPV infection with a liquid based-cytology test and a novel HPV test using the PCR-SSOP-Luminex((r)) method identifying 31 HPV genotypes. In 3,047 normal subjects, the overall prevalence across all HPV types was 25%, while that of the common 13 high-risk (Common-13HR) types (HPV-16, 18. 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) was 17%, and that of the definite high-risk (Definite-HR) types (HPV-16, 18. 31, 33, 35, 45, 52, and 58) was 12%. For Definite-HR, HPV-52, 16, and 58 were the most common, HPV-31 was relatively common, and HPV-18 was less common, while HPV 33, 35, and 45 were rare. Seven Definite-HR excluding HPV-45 and seven Possible HR (HPV-39, 51, 56, 66, 68, 70, and 82) HPV types were identified as a single type infection in patients with high-grade squamous intraepithelial lesion (HSIL) or worse. The Common-13HR types were detected in 89% of subjects with HSIL, whereas either Definite-HR or Possible-HR types were detected in 95% of HSIL. These 1420 HPV types appear to be involved with HSIL or worse in Japan. The prevalences of multiple-type HPV infections were identified in roughly half of HPV-positive subjects, and decreased significantly with age in normal population and abnormal cytology groups, although the prevalences of single-type infections increased with age in the latter group. Most HPV infections are cleared for some years, while a certain HR-HPV type persists to induce HSIL. PMID- 26147988 TI - Studying Hospitalizations and Mortality in the Netherlands: Feasible and Valid Using Two-Step Medical Record Linkage with Nationwide Registers. AB - In the Netherlands, the postal code is needed to study hospitalizations of individuals in the nationwide hospitalization register. Studying hospitalizations longitudinally becomes troublesome if individuals change address. We aimed to report on the feasibility and validity of a two-step medical record linkage approach to examine longitudinal trends in hospitalizations and mortality in a study cohort. First, we linked a study cohort of 1564 survivors of childhood cancer with the Municipal Personal Records Database (GBA) which has postal code history and mortality data available. Within GBA, we sampled a reference population matched on year of birth, gender and calendar year. Second, we extracted hospitalizations from the Hospital Discharge Register (LMR) with a date of discharge during unique follow-up (based on date of birth, gender and postal code in GBA). We calculated the agreement of death and being hospitalized in survivors according to the registers and to available cohort data. We retrieved 1477 (94%) survivors from GBA. Median percentages of unique/potential follow-up were 87% (survivors) and 83% (reference persons). Characteristics of survivors and reference persons contributing to unique follow-up were comparable. Agreement of hospitalization during unique follow-up was 94% and agreement of death was 98%. In absence of unique identifiers in the Dutch hospitalization register, it is feasible and valid to study hospitalizations and mortality of individuals longitudinally using a two-step medical record linkage approach. Cohort studies in the Netherlands have the opportunity to study mortality and hospitalization rates over time. These outcomes provide insight into the burden of clinical events and healthcare use in studies on patients at risk of long-term morbidities. PMID- 26147987 TI - Trends in AIDS Deaths, New Infections and ART Coverage in the Top 30 Countries with the Highest AIDS Mortality Burden; 1990-2013. AB - BACKGROUND: Antiretroviral therapy (ART) prevents human immunodeficiency virus (HIV) disease progression, mortality and transmission. We assess the impact of expanded HIV treatment for the prevention of Acquired Immunodeficiency Syndrome (AIDS)-related deaths and simulate four treatment scenarios for Nigeria and South Africa. METHODS: For 1990-2013, we used the Joint United Nations Programme on HIV/AIDS (UNAIDS) database to examine trends in AIDS deaths, HIV incidence and prevalence, ART coverage, annual AIDS death rate, AIDS death-to-treatment and HIV infections to treatment ratios for the top 30 countries with the highest AIDS mortality burden and compare them with data from high-income countries. We projected the 1990-2020 AIDS deaths for Nigeria and South Africa using four treatment scenarios: 1) no ART; 2) maintaining current ART coverage; 3) 90% ART coverage based on 2013 World Health Organization (WHO) ART guidelines by 2020; and 4) reaching the United Nations 90-90-90 Target by 2020. FINDINGS: In 2013, there were 1.3 million (1.1 million-1.6 million) AIDS deaths in the top 30 countries representing 87% of global AIDS deaths. Eight countries accounted for 58% of the global AIDS deaths; Nigeria and South Africa accounted for 27% of global AIDS deaths. The highest death rates per 1000 people living with HIV were in Central African Republic (91), South Sudan (82), Cote d'Ivoire (75), Cameroon (72) and Chad (71), nearly 8-10 times higher than the high-income countries. ART access in 2013 has averted as estimated 1,051,354 and 422,448 deaths in South Africa and Nigeria, respectively. Increasing ART coverage in these two countries to meet the proposed UN 90-90-90 Target by 2020 could avert 2.2 and 1.2 million deaths, respectively. INTERPRETATION: Over the past decade the expansion of access to ART averted millions of deaths. Reaching the proposed UN 90-90-90 Target by 2020 will prevent additional morbidity, mortality and HIV transmission. Despite progress, high-burden countries will need to accelerate access to ART treatment to avert millions of premature AIDS deaths and new HIV infections. PMID- 26147989 TI - The NOD2 Single Nucleotide Polymorphism rs72796353 (IVS4+10 A>C) Is a Predictor for Perianal Fistulas in Patients with Crohn's Disease in the Absence of Other NOD2 Mutations. AB - BACKGROUND: A previous study suggested an association of the single nucleotide polymorphism (SNP) rs72796353 (IVS4+10 A>C) in the NOD2 gene with susceptibility to Crohn's disease (CD). However, this finding has not been confirmed. Given that NOD2 variants still represent the most important predictors for CD susceptibility and phenotype, we evaluated the association of rs72796353 with inflammatory bowel disease (IBD) susceptibility and the IBD phenotype. METHODOLOGY: Genomic DNA from 2256 Caucasians, including 1073 CD patients, 464 patients with ulcerative colitis (UC), and 719 healthy controls, was genotyped for the NOD2 SNP rs72796353 and the three main CD-associated NOD2 mutations rs2066844, rs2066845, and rs2066847. Subsequently, IBD association and genotype-phenotype analyses were conducted. RESULTS: In contrast to the strong associations of the NOD2 SNPs rs2066844 (p=3.51 x 10(-3)), rs2066845 (p=1.54 x 10(-2)), and rs2066847 (p=1.61 x 10(-20)) with CD susceptibility, no significant association of rs72796353 with CD or UC susceptibility was found. However, in CD patients without the three main CD associated NOD2 mutations, rs72796353 was significantly associated with the development of perianal fistulas (p=2.78 x 10(-7), OR 5.27, [95% CI 2.75-10.12] vs. NOD2 wild-type carriers). CONCLUSION/SIGNIFICANCE: Currently, this study represents the largest genotype-phenotype analysis of the impact of the NOD2 variant rs72796353 on the disease phenotype in IBD. Our data demonstrate that in CD patients the IVS4+10 A>C variant is strongly associated with the development of perianal fistulas. This association is particularly pronounced in patients who are not carriers of the three main CD-associated NOD2 mutations, suggesting rs72796353 as additional genetic marker for the CD disease behaviour. PMID- 26147991 TI - Engineering and Validation of a Vector for Concomitant Expression of Rare Transfer RNA (tRNA) and HIV-1 nef Genes in Escherichia coli. AB - Relative ease in handling and manipulation of Escherichia coli strains make them primary candidate to express proteins heterologously. Overexpression of heterologous genes that contain codons infrequently used by E. coli is related with difficulties such as mRNA instability, early termination of transcription and/or translation, deletions and/or misincorporation, and cell growth inhibition. These codon bias -associated problems are addressed by co-expressing ColE1-compatible, rare tRNA expressing helper plasmids. However, this approach has inadequacies, which we have addressed by engineering an expression vector that concomitantly expresses the heterologous protein of interest, and rare tRNA genes in E. coli. The expression vector contains three (argU, ileY, leuW) rare tRNA genes and a useful multiple cloning site for easy in-frame cloning. To maintain the overall size of the parental plasmid vector, the rare tRNA genes replaced the non-essential DNA segments in the vector. The cloned gene is expressed under the control of T7 promoter and resulting recombinant protein has a C-terminal 6His tag for IMAC-mediated purification. We have evaluated the usefulness of this expression vector by expressing three HIV-1 genes namely HIV-1 p27 (nef), HIV-1 p24 (ca), and HIV-1 vif in NiCo21(DE3) E.coli and demonstrated the advantages of using expression vector that concomitantly expresses rare tRNA and heterologous genes. PMID- 26147990 TI - Oxidized LDL and Fructosamine Associated with Severity of Coronary Artery Atherosclerosis in Insulin Resistant Pigs Fed a High Fat/High NaCl Diet. AB - BACKGROUND: Insulin-resistant subjects develop more severe and diffuse coronary artery atherosclerosis than insulin-sensitive controls but the mechanisms that mediate this atherosclerosis phenotype are unknown. RESEARCH OBJECTIVE: To determine the metabolic parameters that associate with the severity of coronary atherosclerosis in insulin resistant pigs fed a high fat/high NaCl diet. KEY METHODS: The primary endpoint was severity of coronary atherosclerosis in adult pigs (Sus scrofa, n = 37) fed a high fat diet that also contained high NaCl (56% above recommended levels) for 1 year. PRINCIPAL FINDINGS: Twenty pigs developed severe and diffuse distal coronary artery atherosclerosis (i.e., severe = intimal area as a percent medial area > 200% in at least 2 coronary artery cross sections and diffuse distal = intimal area as a percent medial area >= 150% over 3 sections separated by 2 cm in the distal half of the coronary artery). The other 17 pigs had substantially less coronary artery atherosclerosis. All 37 pigs had blood pressure in a range that would be considered hypertensive in humans and developed elevations in total and LDL and HDL cholesterol, weight gain, increased backfat, and increased insulin resistance (Bergman Si) without overt diabetes. Insulin resistance was not associated with atherosclerosis severity. Five additional pigs fed regular pig chow also developed increased insulin resistance but essentially no change in the other variables and little to no detectible coronary atherosclerosis. Most importantly, the 20 high fat/high NaCl diet-fed pigs with severe and diffuse distal coronary artery atherosclerosis had substantially greater increases (p< 0.05) in oxidized LDL (oxLDL) and fructosamine consistent with increased protein glycation. CONCLUSION: In pigs fed a high fat/high NaCl diet, glycated proteins are induced in the absence of overt diabetes and this degree of increase is associated with the development of severe and diffuse distal coronary artery atherosclerosis. PMID- 26147992 TI - Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families. AB - Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 - 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier. PMID- 26147993 TI - Performance of Smokers with DSM-5 Tobacco Use Disorder in Time-Based Complex Prospective Memory. AB - Studies that investigate time-based complex prospective memory (PM) functioning in participants with substance use disorders (SUD) in consideration of different PM-phases (planning, retention, initiation, execution) are lacking. This study was designed to investigate performance of young adults with DSM-5 tobacco use disorder (TUD) and healthy controls (HC) in different phases of complex PM. Community participants aged 18-35 (N=43) completed the modified Six Elements Test that includes the PM-phases planning, retention, initiation, and execution of a time-based complex PM-task (with delay phases and background activities). TUD participants were current daily smokers and fulfilled at least two DSM-5 TUD criteria. TUD did not differ significantly from HC in task planning errors and timely task initiation. No group differences showed in rule adherence and completeness during task conduction (execution). During execution, TUD showed significantly more deviations (Coef. 0.45; p=0.005) from their originally remembered plans than HC. Young adults with relatively mild TUD do not show general impairments in all phases of short-term, complex, and time-based PM. Future research may investigate whether a greater risk of deviation from originally remembered plans in TUD could play a role in the progression and cessation of smoking behavior. PMID- 26147994 TI - Intravenous Tissue Plasminogen Activator Can Be Safely Given without Complete Blood Count Results Back. AB - INTRODUCTION: It is well known that the efficacy of intravenous (i.v.) tissue plasminogen activator (tPA) is time-dependent when used to treat patients with acute ischemic strokes. AIM: Our study examines the safety issue of giving IV tPA without complete blood count (CBC) resulted. MATERIALS AND METHODS: This is a retrospective observational study by examining the database from Huashan Hospital in China and OSF/INI Comprehensive Stroke Center in United States. Patient data collected included demographics, occurrence of symptomatic intracranial hemorrhage, door to needle intervals, National Institute of Health Stroke Scale scores on admission, CBC results on admission and follow-up modified Rankin Scale scores. Linear regression and multivariable logistic regression analysis were used to identify factors that would have an impact on door-to-needle intervals. RESULTS: Our study included 120 patients from Huashan Hospital and 123 patients from INI. Among them, 36 in Huashan Hospital and 51 in INI received i.v. tPA prior to their CBC resulted. Normal platelet count was found in 98.8% patients after tPA was given. One patient had thrombocytopenia but no hemorrhagic event. A significantly shorter door to needle interval (DTN) was found in the group without CBC resulted. There was also a difference in treatment interval between the two hospitals. Door to needle intervals had a strong correlation to onset to treatment intervals and NIHSS scores on admission. CONCLUSION: In patients presented with acute ischemic stroke, the risk of developing hemorrhagic event is low if i.v. tPA is given before CBC has resulted. The door to needle intervals can be significantly reduced. PMID- 26147995 TI - Morphologic and Hemodynamic Analysis in the Patients with Multiple Intracranial Aneurysms: Ruptured versus Unruptured. AB - BACKGROUND AND PURPOSE: The authors evaluated the impact of morphologic and hemodynamic factors on multiple intracranial aneurysms and aimed to identify which parameters can be reliable indexes as one aneurysm ruptured, and the others did not. METHODS: Between June 2011 and May 2014, 69 patients harboring multiple intracranial aneurysms (69 ruptured and 86 unruptured) were analyzed from 3D digital subtraction angiography (DSA) images and computational fluid dynamics (CFD). Morphologic and hemodynamic parameters were evaluated for significance with respect to rupture. Receiver operating characteristic (ROC) analysis identified area under the curve (AUC) and optimal thresholds separating ruptured from unruptured intracranial aneurysms for each parameter. Significant parameters were examined by binary logistic regression analysis to identify independent discriminators. RESULTS: Nine morphologic (size, neck width, surface area, volume, diameter of parent arteries, aspect ratio, size ratio, lateral/bifurcation type and regular/irregular type) and 6 hemodynamic (WSSmean, WSSmin, OSI, LSA, flow stability and flow complexity) parameters achieved statistical significance (p<0.05). Six morphologic (size, surface area, volume, aspect ratio, size ratio and regular/irregular type) and five hemodynamic (WSSmean, WSSmin, LSA, flow stability and flow complexity) parameters had high AUC values (AUC>0.7). By binary logistic regression analysis, large aspect ratio and low WSSmean were the independently significant rupture factors (AUC, 0.924; 95% CI, 0.883-0.965). CONCLUSIONS: Large aspect ratio and low WSSmean were independently associated with the rupture status of multiple intracranial aneurysms. PMID- 26147996 TI - Patterns of Congenital Malformations and Barriers to Care in Eastern Democratic Republic of Congo. AB - BACKGROUND: An increase of congenital anomalies in the eastern Democratic Republic of the Congo (DRC) has been reported. Congenital malformations (CMs) are not uncommon among newborns and, if left untreated, can contribute to increased neonate morbidity and mortality. METHODS: Medical records of all individuals admitted with a diagnosed CM to HEAL Africa Teaching Hospital (Goma, DRC) from 2002 to 2014 (n=1301) were reviewed. Data were analysed using descriptive statistics to summarize chart records, and inferential statistics to investigate significant barriers to earlier treatment. RESULTS: Since 2012, the number of patients treated each year for CMs has increased by over 200% compared to the average annual number of cases treated from 2002-2011. Though delayed presentation of patients to HEAL Hospital was very obvious, with an average age of 8.2 years. We find that patient age has been significantly decreasing (p=0.037) over time. The average distance separating patients from HEAL Hospital was 178 km, with approximately one third living 350 km or further from the treatment center. Distance is the most significant (p=3.33x10(-6)) barrier to earlier treatment. When controlling for an interaction between gender and the use of mercy funds, we also find that female patients are at a significant (p=1.04x10(-3)) disadvantage to undergo earlier corrective surgery. This disadvantage is further illustrated by our finding that 89% of women and girls, and over 81% of all patients, required mercy funds to cover the cost of surgery in 2014. Lastly, the mortality rate for surgery was low and averaged less than 1.0%. CONCLUSION: Despite a formal end to the war in 2009, and an overall increase in individuals undergoing corrective surgery, distance, poverty, and gender are still massive barriers to CM care at HEAL Hospital, Goma, DRC. We find that patients have been successfully treated earlier by HEAL, although the average age of CM correction in 2014 (4.9 years) is still above average for Sub Saharan Africa. Thus, we advocate for further funding from the National Government and international health agencies to enable continued treatment of CMs in rural residents of the eastern DRC. Distance, the most significant barrier to care can be mitigated by the implementation of additional mobile clinics and the construction of regional surgery centers along with the associated hiring of surgeons trained in CM repair. PMID- 26147997 TI - Biomolecular Interaction Analysis Using an Optical Surface Plasmon Resonance Biosensor: The Marquardt Algorithm vs Newton Iteration Algorithm. AB - Kinetic analysis of biomolecular interactions are powerfully used to quantify the binding kinetic constants for the determination of a complex formed or dissociated within a given time span. Surface plasmon resonance biosensors provide an essential approach in the analysis of the biomolecular interactions including the interaction process of antigen-antibody and receptors-ligand. The binding affinity of the antibody to the antigen (or the receptor to the ligand) reflects the biological activities of the control antibodies (or receptors) and the corresponding immune signal responses in the pathologic process. Moreover, both the association rate and dissociation rate of the receptor to ligand are the substantial parameters for the study of signal transmission between cells. A number of experimental data may lead to complicated real-time curves that do not fit well to the kinetic model. This paper presented an analysis approach of biomolecular interactions established by utilizing the Marquardt algorithm. This algorithm was intensively considered to implement in the homemade bioanalyzer to perform the nonlinear curve-fitting of the association and disassociation process of the receptor to ligand. Compared with the results from the Newton iteration algorithm, it shows that the Marquardt algorithm does not only reduce the dependence of the initial value to avoid the divergence but also can greatly reduce the iterative regression times. The association and dissociation rate constants, ka, kd and the affinity parameters for the biomolecular interaction, KA, KD, were experimentally obtained 6.969*10(5) mL.g(-1).s(-1), 0.00073 s(-1), 9.5466*10(8) mL.g(-1) and 1.0475*10(-9) g.mL(-1), respectively from the injection of the HBsAg solution with the concentration of 16 ng.mL(-1). The kinetic constants were evaluated distinctly by using the obtained data from the curve fitting results. PMID- 26147998 TI - Risk Factors for Prolonged Treatment of Whiplash-Associated Disorders. AB - OBJECTIVES: Whiplash-associated disorders (WAD) are the most common injuries that are associated with car collisions in Japan and many Western countries. However, there is no clear evidence regarding the potential risk factors for poor recovery from WAD. Therefore, we used an online survey of the Japanese population to examine the association between potential risk factors and the persistence of symptoms in individuals with WAD. MATERIALS AND METHODS: An online survey was completed by 127,956 participants, including 4,164 participants who had been involved in a traffic collision. A random sample of the collision participants (n = 1,698) were provided with a secondary questionnaire. From among the 974 (57.4%) respondents to the secondary questionnaire, we selected 183 cases (intractable neck pain that was treated over a period of 6 months) and 333 controls (minor neck pain that was treated within 3 months). Multivariable logistic regression analysis was used to evaluate the potential risk factors for prolonged treatment of WAD. RESULTS: Female sex, the severity of the collision, poor expectations of recovery, victim mentality, dizziness, numbness or pain in the arms, and lower back pain were associated with a poor recovery from WAD. CONCLUSIONS: In the present study, the baseline symptoms (dizziness, numbness or pain in the arms, and lower back pain) had the strongest associations with prolonged treatment for WAD, although the psychological and behavioral factors were also important. These risk factors should be considered when evaluating patients who may have the potential for poor outcomes. PMID- 26147999 TI - Hemoglobin Concentration Affects Electroencephalogram During Cardiopulmonary Bypass: An Indication for Neuro-Protective Values. AB - Hemodilution during cardiopulmonary bypass (CPB) is widely used to decrease transfusion and improve microcirculation but has drawbacks, such as diminished hemoglobin levels. Among others, reduced brain oxygenation accounts for neurological adverse outcomes after CPB. The aim of the present study was to ascertain if and how continuous electroencephalogram (EEG) during CPB is affected by hematocrit level and what should be the minimum value to avoid significant frequency band shifts on the EEG. A comparative study design was used with 16 subjects undergoing elective mitral valve repair/replacement. EEG was continuously recorded during the surgical procedure (from anesthesia induction to 20 min after CPB end). Data were marked at relevant time points (T0: before CPB start; T1: after 30 min from CPB beginning; T2: at CPB end), and the following 2 min EEG analyzed with a fast Fourier transform to obtain relative power for delta, theta, alpha, and beta bands. A general linear model for repeated measure was used to study interactions of time (T0, T1, and T2, EEG frequency band, and topographical distribution. The relative powers for each electrode were calculated and represented using topographic maps. Power spectrum differences between time points (T2-T1; T2-T0; T1-T0) were calculated for each electrode, and differences >10%, considered indicative of neuronal sufferance, were included in further analysis. Cutoff hemoglobin values that maximize the proportion of correctly classified EEG band shifts were obtained by previous definition were obtained. At T2, diffuse EEG slowing in delta and theta bands was detected; a minor slowing over anterior regions was evident at T1 for the theta band. Decrements in EEG power greater than 10% were detected only for the delta band at T2. Hemoglobin concentration levels at which no slowing increase was evident were 9.4 mg/dL (Ht: 28.2%) at T1 and 9.2 mg/dL (Ht: 27.6%) at T2. EEG burst suppression pattern related to a lesser degree of slowing at T2. In conclusion, we propose hemoglobin cutoff levels that prevent EEG slowing indicative of neuronal sufferance. In addition, burst-suppression EEG patterns offer higher central nervous system protection as measured on EEG. PMID- 26148000 TI - Role of Heavy Meromyosin in Heat-Induced Gelation in Low Ionic Strength Solution Containing L-Histidine. AB - The gelation of myosin has a very important role in meat products. We have already shown that myosin in low ionic strength solution containing L-histidine forms a transparent gel after heating. To clarify the mechanism of this unique gelation, we investigated the changes in the nature of myosin subfragments during heating in solutions with low and high ionic strengths with and without L histidine. The hydrophobicity of myosin and heavy meromyosin (HMM) in low ionic strength solution containing L-histidine was lower than in high ionic strength solution. The SH contents of myosin and HMM in low ionic strength solution containing l-histidine did not change during the heating process, whereas in high ionic strength solution they decreased slightly. The heat-induced globular masses of HMM in low ionic strength solution containing L-histidine were smaller than those in high ionic strength solution. These findings suggested that the polymerization of HMM molecules by heating was suppressed in low ionic strength solution containing L-histidine, resulting in formation of the unique gel. PMID- 26148001 TI - Isolation of Foreign Material-Free Endothelial Progenitor Cells Using CD31 Aptamer and Therapeutic Application for Ischemic Injury. AB - Endothelial progenitor cells (EPCs) can be isolated from human bone marrow or peripheral blood and reportedly contribute to neovascularization. Aptamers are 40 120-mer nucleotides that bind to a specific target molecule, as antibodies do. To utilize apatmers for isolation of EPCs, in the present study, we successfully generated aptamers that recognize human CD31, an endothelial cell marker. CD31 aptamers bound to human umbilical cord blood-derived EPCs and showed specific interaction with human CD31, but not with mouse CD31. However, CD31 aptamers showed non-specific interaction with CD31-negative 293FT cells and addition of polyanionic competitor dextran sulfate eliminated non-specific interaction without affecting cell viability. From the mixture of EPCs and 293FT cells, CD31 aptamers successfully isolated EPCs with 97.6% purity and 94.2% yield, comparable to those from antibody isolation. In addition, isolated EPCs were decoupled from CD31 aptamers with a brief treatment of high concentration dextran sulfate. EPCs isolated with CD31 aptamers and subsequently decoupled from CD31 aptamers were functional and enhanced the restoration of blood flow when transplanted into a murine hindlimb ischemia model. In this study, we demonstrated isolation of foreign material-free EPCs, which can be utilized as a universal protocol in preparation of cells for therapeutic transplantation. PMID- 26148002 TI - MLgsc: A Maximum-Likelihood General Sequence Classifier. AB - We present software package for classifying protein or nucleotide sequences to user-specified sets of reference sequences. The software trains a model using a multiple sequence alignment and a phylogenetic tree, both supplied by the user. The latter is used to guide model construction and as a decision tree to speed up the classification process. The software was evaluated on all the 16S rRNA gene sequences of the reference dataset found in the GreenGenes database. On this dataset, the software was shown to achieve an error rate of around 1% at genus level. Examples of applications based on the nitrogenase subunit NifH gene and a protein-coding gene found in endospore-forming Firmicutes is also presented. The programs in the package have a simple, straightforward command-line interface for the Unix shell, and are free and open-source. The package has minimal dependencies and thus can be easily integrated in command-line based classification pipelines. PMID- 26148003 TI - Exercise improves cognition in Parkinson's disease: The PRET-PD randomized, clinical trial. AB - BACKGROUND: This article reports on the findings of the effect of two structured exercise interventions on secondary cognitive outcomes that were gathered as part of the Progressive Resistance Exercise Training in Parkinson's disease (PD) randomized, controlled trial. METHODS: This study was a prospective, parallel group, single-center trial. Fifty-one nondemented patients with mild-to-moderate PD were randomly assigned either to modified Fitness Counts (mFC) or to Progressive Resistance Exercise Training (PRET) and were followed for 24 months. Cognitive outcomes were the Digit Span, Stroop, and Brief Test of Attention (BTA). RESULTS: Eighteen patients in mFC and 20 patients in PRET completed the trial. At 12 and at 24 months, no differences between groups were observed. At 12 months, relative to baseline, mFC improved on the Digit Span (estimated change: 0.3; interquartile range: 0, 0.7; P = 0.04) and Stroop (0.3; 0, 0.6; P = 0.04), and PRET improved only on the Digit Span (0.7; 0.3, 1; P < 0.01). At 24 months, relative to baseline, mFC improved on the Digit Span (0.7; 0.3, 1.7; P < 0.01) and Stroop (0.3; 0.1, 0.5; P = 0.03), whereas PRET improved on the Digit Span (0.5; 0.2, 0.8; P < 0.01), Stroop (0.2; -0.1, 0.6; P = 0.048), and BTA (0.3; 0, 0.8; P = 0.048). No neurological or cognitive adverse events were observed. CONCLUSIONS: This study provides class IV level of evidence that 24 months of PRET or mFC may improve attention and working memory in nondemented patients with mild-to-moderate Parkinson's disease. PMID- 26148004 TI - The Mitochondrial Genomes of a Myxozoan Genus Kudoa Are Extremely Divergent in Metazoa. AB - The Myxozoa are oligo-cellular parasites with alternate hosts--fish and annelid worms--and some myxozoan species harm farmed fish. The phylum Myxozoa, comprising 2,100 species, was difficult to position in the tree of life, due to its fast evolutionary rate. Recent phylogenomic studies utilizing an extensive number of nuclear-encoded genes have confirmed that Myxozoans belong to Cnidaria. Nevertheless, the evolution of parasitism and extreme body simplification in Myxozoa is not well understood, and no myxozoan mitochondrial DNA sequence has been reported to date. To further elucidate the evolution of Myxozoa, we sequenced the mitochondrial genomes of the myxozoan species Kudoa septempunctata, K. hexapunctata and K. iwatai and compared them with those of other metazoans. The Kudoa mitochondrial genomes code for ribosomal RNAs, transfer RNAs, eight proteins for oxidative phosphorylation and three proteins of unknown function, and they are among the metazoan mitochondrial genomes coding the fewest proteins. The mitochondrial-encoded proteins were extremely divergent, exhibiting the fastest evolutionary rate in Metazoa. Nevertheless, the dN/dS ratios of the protein genes in genus Kudoa were approximately 0.1 and similar to other cnidarians, indicating that the genes are under negative selection. Despite the divergent genetic content, active oxidative phosphorylation was indicated by the transcriptome, metabolism and structure of mitochondria in K. septempunctata. As possible causes, we attributed the divergence to the population genetic characteristics shared between the two most divergent clades, Ctenophora and Myxozoa, and to the parasitic lifestyle of Myxozoa. The fast-evolving, functional mitochondria of the genus Kudoa expanded our understanding of metazoan mitochondrial evolution. PMID- 26148005 TI - Protective Effects of N-Acetyl Cysteine against Diesel Exhaust Particles-Induced Intracellular ROS Generates Pro-Inflammatory Cytokines to Mediate the Vascular Permeability of Capillary-Like Endothelial Tubes. AB - Exposure to diesel exhaust particles (DEP) is associated with pulmonary and cardiovascular diseases. Previous studies using in vitro endothelial tubes as a simplified model of capillaries have found that DEP-induced ROS increase vascular permeability with rearrangement or internalization of adherens junctional VE cadherin away from the plasma membrane. This allows DEPs to penetrate into the cell and capillary lumen. In addition, pro-inflammatory cytokines are up regulated and mediate vascular permeability in response to DEP. However, the mechanisms through which these DEP-induced pro-inflammatory cytokines increase vascular permeability remain unknown. Hence, we examined the ability of DEP to induce permeability of human umbilical vein endothelial cell tube cells to investigate these mechanisms. Furthermore, supplementation with NAC reduces ROS production following exposure to DEP. HUVEC tube cells contributed to a pro inflammatory response to DEP-induced intracellular ROS generation. Endothelial oxidative stress induced the release of TNF-alpha and IL-6 from tube cells, subsequently stimulating the secretion of VEGF-A independent of HO-1. Our data suggests that DEP-induced intracellular ROS and release of the pro-inflammatory cytokines TNF- alpha and IL-6, which would contribute to VEGF-A secretion and disrupt cell-cell borders and increase vasculature permeability. Addition of NAC suppresses DEP-induced ROS efficiently and reduces subsequent damages by increasing endogenous glutathione. PMID- 26148006 TI - Baseline Platelet Activation and Reactivity in Patients with Critical Limb Ischemia. AB - BACKGROUND: Patients with critical limb ischemia (CLI) have a high risk to develop cardiovascular events (CVE). We hypothesized that in CLI patients platelets would display increased baseline activation and reactivity. OBJECTIVES: We investigated baseline platelet activation and platelet reactivity in patients with CLI. PATIENTS/METHODS: In this study baseline platelet activation and platelet reactivity in response to stimulation of all major platelet activation pathways were determined in 20 CLI patients (11 using aspirin and 9 using vitamin K-antagonists) included in the Juventas-trial (clinicaltrials.gov NCT00371371) and in 17 healthy controls. Platelet activation was quantified with flow cytometric measurement of platelet P-selectin expression and fibrinogen binding. RESULTS: CLI patients not using aspirin showed higher baseline platelet activation compared to healthy controls. Maximal reactivity to stimulation of the collagen and thrombin activation pathway was decreased in CLI patients compared to healthy controls. In line, attenuated platelet reactivity to stimulation of multiple activation pathways was associated with several traditional risk factors for cardiovascular disease. CONCLUSIONS: Baseline platelet activation was increased in CLI patients, whereas the reactivity of circulating platelets to several stimulatory agents is decreased. Reactivity of platelets was inversely correlated with cardiovascular risk factors. PMID- 26148008 TI - Development and Validation of Chinese Health Literacy Scale for Low Salt Consumption-Hong Kong Population (CHLSalt-HK). AB - Globally, sodium intake far exceeds the level recommended by the World Health Organization. Assessing health literacy related to salt consumption among older adults could guide the development of interventions that target their knowledge gaps, misconceptions, or poor dietary practices. This study aimed to develop and validate the Chinese Health Literacy Scale for Low Salt Consumption-Hong Kong population (CHLSalt-HK). Based on previous studies on salt intake and nutrition label reading in other countries, we developed similar questions that were appropriate for the Chinese population in Hong Kong. The questions covered the following eight broad areas: functional literacy (term recognition and nutrition label reading), knowledge of the salt content of foods, knowledge of the diseases related to high salt intake, knowledge of international standards, myths about salt intake, attitudes toward salt intake, salty food consumption practices, and nutrition label reading practices. Eight professionals, including doctors, nurses, and dietitians, provided feedback on the scale. The psychometric properties of the scale were assessed based on data collected from a convenience sample of 603 Chinese elderly adults recruited from Elderly Health Centres in Hong Kong. The 49-item CHLSalt-HK had a possible score range of 0 to 98, with a higher score indicating higher health literacy related to salt intake. The CHLSalt-HK had acceptable content validity; the item-level Content Validity Index ranged from 0.857 to 1.000, and the scale-level Content Validity Index was 0.994. Additionally, it had good internal consistency (Cronbach's alpha of 0.799) and good test-retest reliability (intraclass correlation coefficient of 0.846). The mean CHLSalt-HK score among those who were aware of the public education slogan about nutrition labels and sodium intake was higher by 3.928 points (95% confidence interval: 1.742 to 6.115) than that among those who were not aware of the slogan, which supports adequate discriminant validity. The validated CHLSalt HK had acceptable content validity, acceptable construct validity, good internal consistency, good test-retest reliability, and adequate discriminant validity. The scale could be completed in 10-15 minutes and is easy to administer compared with the collection of biomarkers or food diaries. Further research should investigate its concurrent validity and predictive validity. The development of this scale supports the first step in salt intake reduction among older Chinese adults in Hong Kong by enabling the assessment of their health literacy related to salt consumption in health screenings or health assessments, and it can be used to evaluate salt reduction interventions. PMID- 26148009 TI - Cognition and the Placebo Effect--Dissociating Subjective Perception and Actual Performance. AB - The influence of positive or negative expectations on clinical outcomes such as pain relief or motor performance in patients and healthy participants has been extensively investigated for years. Such research promises potential benefit for patient treatment by deliberately using expectations as means to stimulate endogenous regulation processes. Especially regarding recent interest and controversies revolving around cognitive enhancement, the question remains whether mere expectancies might also yield enhancing or impairing effects in the cognitive domain, i.e., can we improve or impair cognitive performance simply by creating a strong expectancy in participants about their performance? Moreover, previous literature suggests that especially subjective perception is highly susceptible to expectancy effects, whereas objective measures can be affected in certain domains, but not in others. Does such a dissociation of objective measures and subjective perception also apply to cognitive placebo and nocebo effects? In this study, we sought to investigate whether placebo and nocebo effects can be evoked in cognitive tasks, and whether these effects influence objective and subjective measures alike. To this end, we instructed participants about alleged effects of different tone frequencies (high, intermediate, low) on brain activity and cognitive functions. We paired each tone with specific success rates in a Flanker task paradigm as a preliminary conditioning procedure, adapted from research on placebo hypoalgesia. In a subsequent test phase, we measured reaction times and success rates in different expectancy conditions (placebo, nocebo, and control) and then asked participants how the different tone frequencies affected their performance. Interestingly, we found no effects of expectation on objective measures, but a strong effect on subjective perception, i.e., although actual performance was not affected by expectancy, participants strongly believed that the placebo tone frequency improved their performance. PMID- 26148010 TI - Modeling Honey Bee Populations. AB - Eusocial honey bee populations (Apis mellifera) employ an age stratification organization of egg, larvae, pupae, hive bees and foraging bees. Understanding the recent decline in honey bee colonies hinges on understanding the factors that impact each of these different age castes. We first perform an analysis of steady state bee populations given mortality rates within each bee caste and find that the honey bee colony is highly susceptible to hive and pupae mortality rates. Subsequently, we study transient bee population dynamics by building upon the modeling foundation established by Schmickl and Crailsheim and Khoury et al. Our transient model based on differential equations accounts for the effects of pheromones in slowing the maturation of hive bees to foraging bees, the increased mortality of larvae in the absence of sufficient hive bees, and the effects of food scarcity. We also conduct sensitivity studies and show the effects of parameter variations on the colony population. PMID- 26148007 TI - Ad35.CS.01-RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naive Adults. AB - METHODS: In an observer blind, phase 2 trial, 55 adults were randomized to receive one dose of Ad35.CS.01 vaccine followed by two doses of RTS,S/AS01 (ARR group) or three doses of RTS,S/AS01 (RRR-group) at months 0, 1, 2 followed by controlled human malaria infection. RESULTS: ARR and RRR vaccine regimens were well tolerated. Efficacy of ARR and RRR groups after controlled human malaria infection was 44% (95% confidence interval 21%-60%) and 52% (25%-70%), respectively. The RRR-group had greater anti-CS specific IgG titers than did the ARR-group. There were higher numbers of CS-specific CD4 T-cells expressing > 2 cytokine/activation markers and more ex vivo IFN-gamma enzyme-linked immunospots in the ARR-group than the RRR-group. Protected subjects had higher CS-specific IgG titers than non-protected subjects (geometric mean titer, 120.8 vs 51.8 EU/ml, respectively; P = .001). CONCLUSIONS: An increase in vaccine efficacy of ARR-group over RRR-group was not achieved. Future strategies to improve upon RTS,S-induced protection may need to utilize alternative highly immunogenic prime boost regimens and/or additional target antigens. TRIAL REGISTRATION: ClinicalTrials.gov NCT01366534. PMID- 26148011 TI - Can geometric indices of heart rate variability predict improvement in autonomic modulation after resistance training in chronic obstructive pulmonary disease? AB - Chronic obstructive pulmonary disease (COPD) is associated with autonomic dysfunctions that can be evaluated through heart rate variability (HRV). Resistance training promotes improvement in autonomic modulation; however, studies that evaluate this scenario using geometric indices, which include nonlinear evaluation, thus providing more accurate information for physiological interpretation of HRV, are unknown. This study aimed to investigate the influence of resistance training on autonomic modulation, using geometric indices of HRV, and peripheral muscle strength in individuals with COPD. Fourteen volunteers with COPD were submitted to resistance training consisting of 24 sessions lasting 60 min each, with a frequency of three times a week. The intensity was determined as 60% of one maximum repetition and was progressively increased until 80% for the upper and lower limbs. The HRV and dynamometry were performed at two moments, the beginning and the end of the experimental protocol. Significant increases were observed in the RRtri (4.81 +/- 1.60 versus 6.55 +/- 2.69, P = 0.033), TINN (65.36 +/- 35.49 versus 101.07 +/- 63.34, P = 0.028), SD1 (7.48 +/- 3.17 versus 11.04 +/- 6.45, P = 0.038) and SD2 (22.30 +/- 8.56 versus 32.92 +/- 18.78, P = 0.022) indices after the resistance training. Visual analysis of the Poincare plot demonstrated greater dispersion beat-to-beat and in the long-term interval between consecutive heart beats. Regarding muscle strength, there was a significant increase in the shoulder abduction and knee flexion. In conclusion, geometric indices of HRV can predict improvement in autonomic modulation after resistance training in individuals with COPD; improvement in peripheral muscle strength in patients with COPD was also observed. PMID- 26148012 TI - Gold Nanoparticle-Photosensitizer Conjugate Based Photodynamic Inactivation of Biofilm Producing Cells: Potential for Treatment of C. albicans Infection in BALB/c Mice. AB - BACKGROUND: Photodynamic therapy (PDT) has been found to be effective in inhibiting biofilm producing organisms. We investigated the photodynamic effect of gold nanoparticle (GNP) conjugated photosensitizers against Candida albicans biofilm. We also examined the photodynamic efficacy of photosensitizer (PS) conjugated GNPs (GNP-PS) to treat skin and oral C. albicans infection in BALB/c mice. METHODS: The biomimetically synthesized GNPs were conjugated to photosensitizers viz. methylene blue (MB) or toluidine blue O (TB). The conjugation of PSs with GNPs was characterized by spectroscopic and microscopic techniques. The efficacy of gold nanoparticle conjugates against C. albicans biofilm was demonstrated by XTT assay and microscopic studies. The therapeutic efficacy of the combination of the GNP conjugates against cutaneous C. albicans infection was examined in mouse model by enumerating residual fungal burden and histopathological studies. RESULTS: The GNP-PS conjugate based PDT was found to effectively kill both C. albicans planktonic cells and biofilm populating hyphal forms. The mixture of GNPs conjugated to two different PSs significantly depleted the hyphal C. albicans burden against superficial skin and oral C. albicans infection in mice. CONCLUSION: The GNP-PS conjugate combination exhibits synergism in photodynamic inactivation of C. albicans. The GNP conjugate based PDT can be employed effectively in treatment of cutaneous C. albicans infections in model animals. The antibiofilm potential of PDT therapy can also be exploited in depletion of C. albicans on medical appliances such as implants and catheters etc. PMID- 26148014 TI - Is it possible to increase n-3 fatty acid content of meat without affecting its technological and/or sensory quality and the growing performance of chickens? AB - The aim of this study was to increase the content of n-3 fatty acids (FA) of meat without affecting its sensory and/or technological properties or the growth performance of chickens reared under standard conditions. Male chickens, Ross 308, were distributed into 5 groups corresponding to 5 different diets for the growing and finishing periods: control (T), containing extruded linseeds exhibiting high concentration of fibre (ELHF), extruded linseeds exhibiting low concentration of fibre (ELLF), microalgae, or an association of 75% ELLF and 25% MA (ELLF+MA). The diet containing microalgae induced a decrease in feed consumption without affecting growth rate. Chickens exhibited a lower feed conversion ratio than the other groups for the growing and finishing periods but also the whole rearing period. The use of linseeds in diets had no effect on the growth performance of chickens in comparison to the control group. The dietary enrichment with n-3 FA had few effects on carcass composition or the ultimate pH and colour of breast meat. The microalgae increased the meat susceptibility to oxidation. The lipid content of breast meat was not affected by the diets. The breast meat of chickens fed on diets containing linseeds and/or microalgae had greater n-3 FA content (2.4 to 3.9 times higher than group T). The linseeds and microalgae mainly increased the contents in linolenic acid and long chain n-3 FA, respectively. Dietary enrichment with n-3 FA had no effect on the sensory quality of fillets whereas the thighs of the MA group exhibited the lowest score for the flavour "chicken" and the greatest score for the flavour "abnormal" corresponding to a fish flavour. PMID- 26148013 TI - Specialized Cortex Glial Cells Accumulate Lipid Droplets in Drosophila melanogaster. AB - Lipid droplets (LDs) are common organelles of the majority of eukaryotic cell types. Their biological significance has been extensively studied in mammalian liver cells and white adipose tissue. Although the central nervous system contains the highest relative amount and the largest number of different lipid species, neither the spatial nor the temporal distribution of LDs has been described. In this study, we used the brain of the fruitfly, Drosophila melanogaster, to investigate the neuroanatomy of LDs. We demonstrated that LDs are exclusively localised in glial cells but not in neurons in the larval nervous system. We showed that the brain's LD pool, rather than being constant, changes dynamically during development and reaches its highest value at the beginning of metamorphosis. LDs are particularly enriched in cortex glial cells located close to the brain surface. These specialized superficial cortex glial cells contain the highest amount of LDs among glial cell types and encapsulate neuroblasts and their daughter cells. Superficial cortex glial cells, combined with subperineurial glial cells, express the Drosophila fatty acid binding protein (Dfabp), as we have demonstrated through light- and electron microscopic immunocytochemistry. To the best of our best knowledge this is the first study that describes LD neuroanatomy in the Drosophila larval brain. PMID- 26148015 TI - Nucleolin enhances the proliferation and migration of heat-denatured human dermal fibroblasts. AB - Denatured dermis, a part of dermis in burned skin, has the ability to restore its normal morphology and functions after their surrounding microenvironment is improved. However, the cellular and molecular mechanisms by which the denatured dermis could improve wound healing are still unclear. This study aimed to investigate the role of nucleolin during the recovery of heat-denatured human dermal fibroblasts. Nucleolin mRNA and protein expression were significantly increased time-dependently during the recovery of heat-denatured human dermal fibroblasts (52 degrees C, 30 seconds). Heat-denaturation promoted a time dependent cell proliferation, migration, chemotaxis, and scratched wound healing during the recovery of human dermal fibroblasts. These effects were prevented by knockdown of nucleolin expression with small interference RNA (siRNA), whereas overexpression of nucleolin enhanced cell proliferation, migration, and chemotaxis of human dermal fibroblasts with heat-denaturation. In addition, the expression of transforming growth factor-beta 1(TGF-beta1) was significantly increased during the recovery of heat-denatured dermis and human dermal fibroblasts. TGF-beta1 expression was up-regulated by nucleolin in human dermal fibroblasts. The results suggest that nucleolin expression is up-regulated, and play an important role in promoting cell proliferation, migration, and chemotaxis of human dermal fibroblasts during the recovery of heat-denatured dermis with a mechanism probably related to TGF-beta1. PMID- 26148016 TI - Service users' experiences of participation in decision making in mental health services. AB - ACCESSIBLE SUMMARY: Despite the potential positive impact of shared decision making on service users knowledge and experience of decisional conflict, there is a lack of qualitative research on how participation in decision making is promoted from the perspective of psychiatric service users. This study highlights the desire of users to participate more actively in decision making and demonstrates that persons with SMI struggle to be seen as competent and equal partners in decision-making situations. Those interviewed did not feel that their strengths, abilities and needs were being recognized, which resulted in a feeling of being omitted from involvement in decision-making situations. The service users describe some essential conditions that could work to promote participation in decision making. These included having personal support, having access to knowledge, being involved in a dialogue and clarity about responsibilities. Mental health nurses can play an essential role for developing and implementing shared decision making as a tool to promote recovery-oriented mental health services. ABSTRACT: Service user participation in decision making is considered an essential component of recovery-oriented mental health services. Despite the potential of shared decision making to impact service users knowledge and positively influence their experience of decisional conflict, there is a lack of qualitative research on how participation in decision making is promoted from the perspective of psychiatric service users. In order to develop concrete methods that facilitate shared decision making, there is a need for increased knowledge regarding the users' own perspective. The aim of this study was to explore users' experiences of participation in decisions in mental health services in Sweden, and the kinds of support that may promote participation. Constructivist Grounded Theory (CGT) was utilized to analyse group and individual interviews with 20 users with experience of serious mental illness. The core category that emerged in the analysis described a 'struggle to be perceived as a competent and equal person' while three related categories including being the underdog, being controlled and being omitted described the difficulties of participating in decisions. The data analysis resulted in a model that describes internal and external conditions that influence the promotion of participation in decision making. The findings offer new insights from a user perspective and these can be utilized to develop and investigate concrete methods in order to promote user's participation in decisions. PMID- 26148017 TI - Highly sensitive wide bandwidth photodetector based on internal photoemission in CVD grown p-type MoS2/graphene Schottky junction. AB - Two dimensional (2D) Molybdenum disulfide (MoS2) has evolved as a promising material for next generation optoelectronic devices owing to its unique electrical and optical properties, such as band gap modulation, high optical absorption, and increased luminescence quantum yield. The 2D MoS2 photodetectors reported in the literature have presented low responsivity compared to silicon based photodetectors. In this study, we assembled atomically thin p-type MoS2 with graphene to form a MoS2/graphene Schottky photodetector where photo generated holes travel from graphene to MoS2 over the Schottky barrier under illumination. We found that the p-type MoS2 forms a Schottky junction with graphene with a barrier height of 139 meV, which results in high photocurrent and wide spectral range of detection with wavelength selectivity. The fabricated photodetector showed excellent photosensitivity with a maximum photo responsivity of 1.26 AW(-1) and a noise equivalent power of 7.8 * 10(-12) W/?Hz at 1440 nm. PMID- 26148018 TI - Gluten and casein supplementation does not increase symptoms in children with autism spectrum disorder. AB - AIM: A gluten- and casein-free diet is often given to children with autism spectrum disorder (ASD). We aimed to determine the effect of gluten and casein supplementation on maladaptive behaviour, gastrointestinal symptom severity and intestinal fatty acids binding protein (I-FABP) excretion in children with ASD. METHODS: A randomised, controlled, double-blind trial was performed on 74 children with ASD with severe maladaptive behaviour and increased urinary I-FABP. Subjects were randomised to receive gluten-casein or a placebo for seven days. We evaluated maladaptive behaviour before and after supplementation, using I-FABP excretion, the approach withdrawal problem composite subtest of the Pervasive Developmental Disorder Behavior Inventory and the Gastrointestinal Symptom Severity Index. RESULTS: The mean approach withdrawal problem composite score was significantly higher before supplementation than after, both in the placebo and in the gluten-casein group. However, the mean difference was not significant and may have been caused by additional therapy. There was no significant difference in gastrointestinal symptoms and urinary I-FABP excretion. CONCLUSION: Administrating gluten-casein to children with ASD for one week did not increase maladaptive behaviour, gastrointestinal symptom severity or urinary I-FABP excretion. The effect of prolonged administration or other mechanisms of enterocyte damage in ASD should be explored. PMID- 26148019 TI - Canadian Stroke Best Practice Recommendations: Hyperacute Stroke Care Guidelines, Update 2015. AB - The 2015 update of the Canadian Stroke Best Practice Recommendations Hyperacute Stroke Care guideline highlights key elements involved in the initial assessment, stabilization, and treatment of patients with transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and acute venous sinus thrombosis. The most notable change in this 5th edition is the addition of new recommendations for the use of endovascular therapy for patients with acute ischemic stroke and proximal intracranial arterial occlusion. This includes an overview of the infrastructure and resources required for stroke centers that will provide endovascular therapy as well as regional structures needed to ensure that all patients with acute ischemic stroke that are eligible for endovascular therapy will be able to access this newly approved therapy; recommendations for hyperacute brain and enhanced vascular imaging using computed tomography angiography and computed tomography perfusion; patient selection criteria based on the five trials of endovascular therapy published in early 2015, and performance metric targets for important time-points involved in endovascular therapy, including computed tomography-to-groin puncture and computed tomography-to-reperfusion times. Other updates in this guideline include recommendations for improved time efficiencies for all aspects of hyperacute stroke care with a movement toward a new median target door-to-needle time of 30 min, with the 90th percentile being 60 min. A stronger emphasis is placed on increasing public awareness of stroke with the recent launch of the Heart and Stroke Foundation of Canada FAST signs of stroke campaign; reinforcing the public need to seek immediate medical attention by calling 911; further engagement of paramedics in the prehospital phase with prehospital notification to the receiving emergency department, as well as the stroke team, including neuroradiology; updates to the triage and same-day assessment of patients with transient ischemic attack; updates to blood pressure recommendations for the hyperacute phase of care for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The goal of these recommendations and supporting materials is to improve efficiencies and minimize the absolute time lapse between stroke symptom onset and reperfusion therapy, which in turn leads to better outcomes and potentially shorter recovery times. PMID- 26148021 TI - Re: Ahmed et al.: Impact of varicocelectomy on premature ejaculation (PE) in varicocele patients (Andrologia. 2014, March 10). PMID- 26148020 TI - Assessment of the Impact of Zoledronic Acid on Ovariectomized Osteoporosis Model Using Micro-CT Scanning. AB - PURPOSE/OBJECTIVE: Prompted by preliminary findings, this study was conducted to investigate the impact of zoledronic acid on the cancellous bone microstructure and its effect on the level of beta-catenin in a mouse model of postmenopausal osteoporosis. METHODS AND MATERIALS: 96 8-week-old specific-pathogen-free C57BL/6 mice were randomly divided into 4 groups (24 per group): a sham group, an ovariectomized osteoporosis model group, an estradiol-treated group, and a zoledronic acid-treated group. Five months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro computed tomography (micro-CT) to acquire three-dimensional imagery of their cancellous bone microstructure. The impact of ovariectomy, the effect of estradiol, and the effect of zoledronic acid intervention on cancellous bone microstructure, as well as on the expression of beta-catenin, were evaluated. RESULTS: The estradiol-treated and the zoledronic acid-treated group exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickness, bone surface to bone volume ratio (BS/BV), and beta-catenin expression, when compared with those of the control group (P <0.01). In contrast, the structure model index, trabecular separation, and BS/BV were significantly lower compared with those of the model group (P <0.01). No differences were observed in the above parameters between animals of the zoledronic acid-treated and the estradiol-treated group. CONCLUSION: These results suggest that increased beta-catenin expression may be the mechanism underlying zoledronic acid-related improvement in the cancellous bone microstructure in ovariectomized mice. Our findings provide a scientific rationale for using zoledronic acid as a therapeutic intervention to prevent bone loss in post-menopausal women. PMID- 26148022 TI - Predictors of early response to initial therapy in patients with newly diagnosed symptomatic multiple myeloma. AB - Response to therapy in newly diagnosed symptomatic multiple myeloma (NDMM) can impact long-term outcomes. It is not clear if baseline laboratory parameters can predict an early, deep response. Totally 1,304 patients with NDMM seen between 2001 and 2013 at Mayo Clinic Rochester were studied. The association between baseline laboratory parameters and early, deep response defined as a very good partial response or better (VGPR+) within four cycles of treatment was investigated. Multivariable logistic regression was used to assess the associations between the parameters of interest and response. Multivariable proportional hazards regression was used to assess the association between response and overall survival. In the entire cohort, greater absolute free light chain (FLC) differences (OR 2.38, 95% CI 1.48-3.82), younger age (OR 2.18, 95% CI 1.28-3.71), lower hemoglobin (OR 1.68, 95% CI 1.12-2.54), and IgA myeloma (OR 1.66, 95% CI 1.10-2.51) were associated with increased odds of achieving VGPR+ after four cycles. Among patients receiving novel agents in general and immunomodulators in particular, these effects were more pronounced. In patients receiving proteasome-inhibitors, higher creatinine (OR 3.83, 95% CI 1.37-10.1), lower calcium (OR 3.37, 95% CI 1.36-8.35), and greater absolute FLC differences (OR 2.50, 95% CI 1.10-5.71) were associated with better response. In a landmark analysis at 4 months from diagnosis, achieving VGPR+ was associated with decreased risk of subsequent mortality (HR 0.69, 95% CI 0.53-0.86). In summary, several parameters were associated with an early, deep response to treatment, revealing distinct sets of predictors for immunomodulator- and proteasome inhibitor-containing regimens. Achieving VGPR+ after four cycles translated into increased overall survival. PMID- 26148023 TI - Replication and Analysis of Ebbinghaus' Forgetting Curve. AB - We present a successful replication of Ebbinghaus' classic forgetting curve from 1880 based on the method of savings. One subject spent 70 hours learning lists and relearning them after 20 min, 1 hour, 9 hours, 1 day, 2 days, or 31 days. The results are similar to Ebbinghaus' original data. We analyze the effects of serial position on forgetting and investigate what mathematical equations present a good fit to the Ebbinghaus forgetting curve and its replications. We conclude that the Ebbinghaus forgetting curve has indeed been replicated and that it is not completely smooth but most probably shows a jump upwards starting at the 24 hour data point. PMID- 26148024 TI - Bactericidal Effect of Photolysis of H2O2 in Combination with Sonolysis of Water via Hydroxyl Radical Generation. AB - The bactericidal effect of hydroxyl radical (.OH) generated by combination of photolysis of hydrogen peroxide (H2O2) and sonolysis of water was examined under the condition in which the yield of .OH increased additively when H2O2 aqueous solution was concomitantly irradiated with laser and ultrasound. The suspension of Staphylococcus aureus mixed with the different concentrations of H2O2 was irradiated simultaneously with a laser light (wavelength: 405 nm, irradiance: 46 and 91 mW/cm2) and ultrasound (power: 30 w, frequency: 1.65 MHz) at 20 +/- 1 degrees C of the water bulk temperature for 2 min. The combination of laser and ultrasound irradiation significantly reduced the viable bacterial count in comparison with the laser irradiation of H2O2 alone. By contrast, the ultrasound irradiation alone exerted almost no bactericidal effect. These results suggested that the combination effect of photolysis of H2O2 and sonolysis of water on bactericidal activity was synergistic. A multi-way analysis of variance also revealed that the interaction of H2O2 concentration, laser power and ultrasound irradiation significantly affected the bactericidal activity. Since the result of oxidative DNA damage evaluation demonstrated that the combination of laser and ultrasound irradiation significantly induced oxidative damage of bacterial DNA in comparison with the laser irradiation of H2O2 alone, it was suggested that the combination effect of photolysis of H2O2 and sonolysis of water on bactericidal activity would be exerted via oxidative damage of cellular components such as DNA. PMID- 26148025 TI - qPCR for second year undergraduates: A short, structured inquiry to illustrate differential gene expression. AB - We describe a structured inquiry laboratory exercise that examines transcriptional regulation of the NOS2 gene under conditions that simulate the inflammatory response in macrophages. Using quantitative PCR and the comparative CT method, students are able determine whether transcriptional activation of NOS2 occurs and to what degree. The exercise is aimed at second year undergraduates who possess basic knowledge of gene expression events. It requires only 4-5 hr of dedicated laboratory time and focuses on use of the primary literature, data analysis, and interpretation. Importantly, this exercise provides a mechanism to introduce the concept of differential gene expression and provides a starting point for development of more complex guided or open inquiry projects for students moving into upper level molecular biology, immunology, and biochemistry course work. PMID- 26148027 TI - [The Instituo Nacional de Salud: current setting for research and innovation in public health in Colombia]. PMID- 26148028 TI - [Phenotypic and genotypic diagnosis of bone and miliary tuberculosis in an HIV+ patient in Bogota, Colombia]. AB - Tuberculosis is the single most frequent cause of death by an infectious agent worldwide. Diagnosis of extra-pulmonary tuberculosis is not always possible through conventional methods, due to the long time required for cultures and the paucibacillary nature of samples; hence the need of rapid molecular methods. HIV infection increases the risk of tuberculosis, and HIV/tuberculosis coinfection is associated with higher mortality. We describe the case of a 56-year old mestizo male patient suspected of having tuberculosis who consulted the San Ignacio Hospital in Bogota with a two-month history of a painful ulcerated lesion over the distal third area of the right forearm and in whom HIV coinfection was confirmed. Bone and pulmonary histological examination evidenced multiple granulomas, giant cells and fibrosis. Cultures and IS6110-PCR from lung and bone tissues were positive for Mycobacterium tuberculosis complex. Mycobacterium tuberculosis isolates were sensitive to first line drugs. PMID- 26148026 TI - Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders. AB - Burkholderia pseudomallei and Burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. These bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. Both species are considered potential agents of biological warfare; they are classified as category B priority pathogens. Currently there are no human or veterinary vaccines available against these pathogens. Consequently efforts are directed towards the development of an efficacious and safe vaccine. Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses. B. mallei express LPS that is structurally similar to that expressed by B. pseudomallei, suggesting the possibility of constructing a single protective vaccine against melioidosis and glanders. Previous studies of others have shown that antibodies against B. mallei or B. pseudomallei LPS partially protect mice against subsequent lethal virulent Burkholderia challenge. In this study, we evaluated the protective efficacy of recombinant Salmonella enterica serovar Typhimurium SL3261 expressing B. mallei O antigen against lethal intranasal infection with Burkholderia thailandensis, a surrogate for biothreat Burkholderia spp. in a murine model that mimics melioidosis and glanders. All vaccine-immunized mice developed a specific antibody response to B. mallei and B. pseudomallei O antigen and to B. thailandensis and were significantly protected against challenge with a lethal dose of B. thailandensis. These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine. PMID- 26148029 TI - [Invasive Streptococcus pneumoniae infection (Austrian syndrome): a case report]. AB - Austrian syndrome is defined as the triad consisting of pneumonia, endocarditis and meningitis due to invasive Streptococcus pneumoniae infection. Few case reports have been reported since its first description in 1975 by Robert Austrian, mainly because it is rarely observed. Below we report the case of a 61 year-old male patient who presented with bacterial meningitis due S. pneumoniae followed by bacterial pneumonia and severe mitral regurgitation, associated with four vegetations on the atrial surface of the posterior mitral leaflet; in addition, there was rupture and prolapse of its middle scallop. The S. pneumoniae bacterium was isolated from cerebrospinal fluid and blood cultures. In consequence, the patient was given broad-spectrum antibiotic therapy and had an early valve replacement performed, obtaining a good clinical outcome. The key prognostic factor of the Austrian syndrome is determined by the damage of cardiac valves, particularly in patients with a compromised aortic valve; hence, it is necessary to identify the degree of valve injury and define surgical and antibiotic treatment on a timely fashion. However, in subacute, less frequent clinical cases where the mitral valve is the main valve compromised, usually a directed antibiotic therapy associated with advanced support measures are sufficient to control this infection. PMID- 26148030 TI - Endoscopic findings of primary follicular lymphoma. AB - A 79-year-old female with benign past medical history presented to the gastroenterology clinic complaining of long-standing symptoms of dyspepsia. Esophagogastroduodenoscopy showed nodular smooth mucosa in the second part of the duodenum. The morphologic and immunophenotypic findings were consistent with low grade follicular lymphoma. The purpose of this manuscript is to educate the reader on this unusual finding that is pathognomonic for gastrointestinal lymphoma. PMID- 26148031 TI - [Outbreak of malaria in an indigenous population living in an urban area of Armenia, Colombia, 2012]. AB - INTRODUCTION: Malaria is the most frequent mosquito-borne parasitic infection in the tropical regions of the world. Due to different factors, including climate change, this disease can emerge or reemerge in different areas in the planet. OBJECTIVE: To describe an autochthonous outbreak of urban malaria in Armenia, Colombia. MATERIALS AND METHODS: After two children consulted a second level hospital located in the south of Armenia with malaria symptoms and their diagnosis was confirmed through the presence of Plasmodium vivax trophozoites detected by a positive thick blood smear, a visit was conducted to the residence of the children. An active search for cases was carried out, the environmental and sociocultural conditions were described and mosquito larvae and pupae were collected and identified. Control measures were implemented and their effectiveness was evaluated as well. RESULTS: The active search in the community allowed the identification of 11 probable cases, three of which were P. vivax malaria cases in children confirmed by blood microscopy. The entomological analysis of mosquito larvae and pupae showed Anopheles spp., Anopheles punctimacula and Anopheles argyritarsis. CONCLUSION: This is the first report of an autochthonous malaria outbreak by P. vivax in the city of Armenia, associated with the subnormal settlement of an indigenous community. The banks of the Quindio river offer the eco-epidemiological conditions that allow the establishment of the reproductive cycle of the malaria mosquito vector. PMID- 26148032 TI - [Characterization of adverse drug reactions in adults over 44 years of age in Bogota, January-December, 2012]. AB - INTRODUCTION: In Colombia, aging of the population is a reality and elders consume more drugs than the young do. Consequently, they are more exposed to adverse drug reactions. OBJECTIVE: To characterize suspected adverse drug reactions in adults over 44 years of age in Bogota in 2012. MATERIALS AND METHODS: We conducted a pharmacological surveillance study that included 470 reports of adverse drug events and associated problems with the use of drugs in adults over 44 years old included in the database of Bogota's pharmacosurveillance program. RESULTS: We evaluated 470 reports of adverse drug events and associated problems with the use of drugs in adults over 44 years of age. From these, 432 reports (91.9%) were classified as suspected adverse drug reactions and 28 (6%), as associated problems with the use of drugs. The incidence rate for adverse drug events reported in Bogota was 22.5 for every 100,000 elders, which increased in direct proportion to patients' age. The most frequently reported drug was antibacterials with 94 notifications (20%). The organ system with the highest number of alterations was the skin and annexes with 21.2% of cases. Regarding severity assessment, 69.5% of adverse drug reactions were moderate, and as for causality, most adverse drug reactions were classified as possible, with 45.8% of the reports. CONCLUSIONS: The characterization of adverse drug reactions in older adults in Bogota is similar to that reported in the literature for this population age group. PMID- 26148033 TI - [Insecticide susceptibility evaluation in Aedes aegypti populations of Caldas, Colombia, in 2007 and 2011]. AB - INTRODUCTION: Continuous use of insecticides for the control of dengue transmission may lead to decreased susceptibility levels in mosquito vector populations. Timely monitoring is necessary to ensure detection of any potential resistance problems. OBJECTIVE: To determine the susceptibility status of Aedes aegypti to insecticides used in public health in Caldas, Colombia, during 2007 and 2011. MATERIALS AND METHODS: Susceptibility tests to the organophosphates temephos, malathion, fenitrothion and pirimiphos methyl, as well as to the pyrethroid deltamethrin, were carried out using standard World Health Organization and Centers for Disease Control and Prevention protocols. RESULTS: In 2007, resistance to temephos was detected in Ae. aegypti populations from La Dorada with resistance ratios of 11.5 and 13.3, prompting the Caldas Health Department to suspend the use of this larvicide. A reduction in resistance ratios to temephos was observed in 2011, as well as an apparent resistance to pirimiphos methyl. All Ae. aegypti populations tested were susceptible to deltamethrin, malathion and fenitrothion in both years. CONCLUSION: Evaluating the resistance ratios during two distinct periods allowed a decrease in resistance to be detected after suspension of the use of temephos. Surveillance of mosquito populations for changes in susceptibility levels to the insecticides used in dengue control programs is therefore recommended. PMID- 26148034 TI - [Microgeographic and temporal genetic changes of Aedes aegypti from Medellin, Colombia]. AB - INTRODUCTION: Aedes aegypti populations may experience changes in abundance and genetic diversity in addition to changes in their evolutionary capability to respond to vector control. The knowledge on the changes in genetic variation on a spatio-temporal scale improves the epidemiological understanding of dengue and supports the appropriate and timely design of vector control strategies. OBJECTIVE: To assess the genetic changes, diversity and gene flow in six microgeographical populations of Ae. aegypti in Medellin for different epidemiological periods of dengue. MATERIALS AND METHODS: A total of 255 specimens from six different neighborhoods in Medellin were used to assess variations in the CO1 mtDNA haplotype composition, diversity and genetic differentiation for an epidemic period (2010) and an endemic period (2012). RESULTS: Two groups of highly differentiated haplotypes were present in both periods, and a high-frequency haplotype was assessed for all neighborhoods. The highest haplotype diversity was recorded in 2012, but the maximum nucleotide diversity was recorded in 2010. No significant correlation between genetic and geographic distances was observed. CONCLUSIONS: The genetic composition of Ae. aegypti varies over time without a predictable pattern. In addition, the presence of a high-frequency haplotype in both periods could indicate a persistent variation adapted to vector control. However, the simultaneous movement of highly differentiated CO1 haplotypes compatible with multiple introductions suggests that different gene pools would be suitable for transmission. These results are consistent with mosquito dispersion due to human activities, which would enable the rapid spread of the virus during epidemics in Medellin. PMID- 26148035 TI - [Do some conditions contribute to the reemergence of the Venezuelan equine encephalitis virus in the Colombian Alta Guajira?]. AB - INTRODUCTION: In the last 18 years, epizootics of Venezuelan equine encephalitis have not occurred in places with historic epidemic register (1925-1995) in the Guajira Peninsula, Colombia. OBJECTIVE: To assess if the Guajira Peninsula, Colombia, still maintains the epidemiological conditions for Venezuelan equine encephalitis virus reemergence. MATERIALS AND METHODS: Research was carried out in places affected by the 1995 epidemic. We evaluated: 1) abundance and seasonal variation of vector mosquito populations; 2) availability of mammals that are potential amplifiers of the virus, and 3) knowledge among the community about the disease and its vectors. RESULTS: Most of the 16 mosquito species were found during the rainy season. Aedes taeniorhynchus and Psorophora confinnis showed direct relation with rainfall and temperature. In contrast, the dominant species, Deinocerites atlanticus , was always present in the collections, regardless of climatic conditions. No IgG antibodies were found in humans younger than 17 years old, goats or bovine sera. One third of those interviewed remembered the last epidemic and had basic understanding of the disease. Only 20% of the families were owners of equines, and 8% was informed of the importance of equine vaccination. CONCLUSIONS: Some epidemiological conditions that eventually could help epizootic Venezuelan equine encephalitis virus reemergence are maintained. However, an abrupt decrease in the number of susceptible equines was found in the area. Apparently, this new condition has not allowed the virus reemergence and is the biggest observed change. PMID- 26148036 TI - [Contextual effects associated with depression risk variability in the elderly, Antioquia, Colombia, 2012]. AB - INTRODUCTION: Depression is an affective disorder where interest in living is lost and functional areas like work, feelings, personal life, and relationships are negatively altered. However, little has been said about the association between place of residence and this mood disorder. OBJECTIVE: To determine the effects of the municipality and block of residence on the depression risk variability in the elderly in the Department of Antioquia, Colombia, in 2012. MATERIALS AND METHODS: This was a multilevel descriptive study of secondary source records of 4,060 elderly people from the Department of Antioquia. Demographic, social and functional characteristics were assessed to calculate raw and adjusted odds ratios and find an association between the risk of depression, as measured by Yesavage's Geriatric Depression Scale, and context variables (municipality and block of residence) in the design of the model. We used Markov chain Monte Carlo estimation methods and the deviance information criterion to assess goodness of fit. RESULTS: The prevalence of the risk of depression was 29.5% and we found an association with ages over 75 years, being female, residing in rural areas, and widowhood. Additionally, they had a higher risk of anxiety, moderate functional capacity and malnutrition. The municipality and block of residence were associated with this risk in the elderly. CONCLUSIONS: The municipality and block of residence had a 10% contribution toward the total variability in the risk of depression for the elderly. This information is important to encourage participation and adherence of the elderly to community groups. PMID- 26148037 TI - Susceptibility of different Rhodnius species (Hemiptera, Reduviidae, Triatominae) to a Brazilian strain of Trypanosoma rangeli (SC58/KP1-). AB - INTRODUCTION: Specific host-parasite associations have been detected experimentally and suggest that triatomines of the genus Rhodnius act as biological filters in the transmission of Trypanosoma rangeli . OBJECTIVE: To analyze the susceptibility of four Rhodnius species ( Rhodnius robustus , Rhodnius neglectus , Rhodnius nasutus and Rhodnius pictipes ) to a Brazilian strain of T. rangeli (SC-58/KP1-). MATERIALS AND METHODS: We selected t hirty nymphs of each species, which were fed on blood infected with T. rangeli . Periodically, samples of feces and hemolymph were analyzed. Triatomines with T. rangeli in their hemolymph were fed on mice to check for transmission by bites. Later, the triatomines were dissected to confirm salivary gland infection. RESULTS: Specimens of R. pictipes showed higher rates of intestinal infection compared to the other three species. Epimastigotes and trypomastigotes were detected in hemolymph of four species; however, parasitism was lower in the species of the R. robustus lineage. Rhodnius robustus and R. neglectus specimens did not transmit T. rangeli by bite; after dissection, their glands were not infected. Only one specimen of R. nasutus and two of R. pictipes transmitted the parasite by bite. The rate of salivary gland infection was 16% for R. pictipes and 4% for R. nasutus . CONCLUSIONS: Both infectivity (intestinal, hemolymphatic and glandular) and transmission of T. rangeli (SC58/KP1-) were greater and more efficient in R. pictipes. These results reinforce the hypothesis that these triatomines may act as biological filters in the transmission of T. rangeli . PMID- 26148038 TI - [Changes in depression and loneliness after laughter therapy in institutionalized elders]. AB - INTRODUCTION: Old age is a stage characterized by a number of factors, such as loneliness and depression, that have a negative effect on people's lives. OBJECTIVE: To evaluate the impact of laughter therapy on the level of depression and loneliness in a group of institutionalized elders. MATERIALS AND METHODS: Exploratory research with quasi-experimental design applying Yesavage depression scale and the ESTE scale of loneliness, both validated for Colombia. The target population consisted of 49 men and women who were 59 years old or over, and lived in the Gerontological Home ''Colonia de Belencito'' in the city of Medellin (Antioquia); they were contacted between April and July 2013, and they received eight sessions of laughter therapy performed by the group "Hospital Clowns" of the Mediclaun Foundation from Medellin. RESULTS: There was a significant decrease in the level of depression especially in those with initial depression established (p<0,032). The most receptive were institutionalized elders who did not have a couple, they were between 65 and 75 years of age, and they belonged to socioeconomic level 2 and did not receive visits. No significant changes in the level of loneliness were recorded. CONCLUSION: The importance of laughter therapy in reducing the level of depression in elders is highlighted. These results agree with the statement indicating that the construct of loneliness is independent from depression. PMID- 26148039 TI - [Common variable immunodeficiency: Clinical and immunological characterization of patients and homogeneous subgroup definition by means of B lymphocyte subpopulation typing]. AB - INTRODUCTION: Common variable immunodeficiency is a heterogeneous syndrome characterized by recurrent infections, hypogammaglobulinemia and defective production of specific antibodies. Abnormalities in peripheral blood lymphocyte subpopulations, in particular of B lymphocytes, allow the classification of patients into homogeneous groups. OBJECTIVE: To perform a clinical and immunological characterization and to evaluate lymphocyte subpopulations of twelve Colombian patients with common variable immunodeficiency in order to define homogeneous groups. MATERIALS AND METHODS: We reviewed medical records and evaluated serum immunoglobulins (Ig), lymphoproliferation, delayed hypersensitivity and used flow cytometry to quantify peripheral blood total lymphocyte and B cell populations. RESULTS: All patients had recurrent respiratory and/or gastrointestinal infections, while some also had infections affecting other systems. All patients had abnormally low serum IgG levels, while IgA and IgM levels were reduced in nine and ten patients, respectively. Lymphoproliferation to mitogen was lower in patients than in healthy controls but lymphoproliferation to specific antigen was normal in all. Flow cytometry revealed high numbers of T cells in three patients, while seven had a low CD4+/CD8+ ratio and four had reduced NK cells . Eleven patients had normal B cell counts, and eight of them also showed decreased memory B lymphocytes, and four had increased transitional or CD21 low B lymphocytes. CONCLUSION: Lymphocyte typing allowed assigning all but one patient to homogeneous groups according to international classification schemes, indicating the necessity of including more criteria until an ideal classification is achieved. This study will lead to a better medical monitoring of common variable immunodeficiency patients in groups at high risk of developing clinical complications. PMID- 26148040 TI - Detection and characterization of multidrug-resistant enterobacteria bearing aminoglycoside-modifying gene in a university hospital at Rio de Janeiro, Brazil, along three decades. AB - INTRODUCTION: Multidrug-resistant Enterobacteriaceae, particularly those resistant to gentamicin, have become one of the most important causes of nosocomial infections. OBJECTIVE: We sought to investigate the presence of genes conferring resistance to aminoglycosides, specially to gentamicin, in Klebsiella pneumoniae and Escherichia coli multidrug-resistant strains isolated from different clinical materials among patients hospitalized in a university hospital in Rio de Janeiro, Brazil. MATERIALS AND METHODS: Ten colonization strains and 20 infection strains were evaluated during three decades (1980 to 2010) using selective media containing 8 ug/ml of gentamicin. Thirty strains were tested for antimicrobial susceptibility. Twenty two strains were subjected to plasmid DNA extraction and 12 to hybridization assays using as probe a 1.9 kb plasmid DNA fragment from one of the K. pneumoniae strains isolated from faecal samples. This fragment was sequenced and assigned to the GQ422439 GenBank record. PCR was also performed using oligonucleotides designed for aminoglycoside-modifying enzymes. RESULTS: An accC2 acetylase, besides transposons and insertion sequences, were evidenced. Twenty-four (80%) of the isolates were positive for the aacC2 gene in agreement with antibiotic susceptibility testing profiles, indicating the persistent presence of this gene throughout the three decades. We detected high molecular weight plasmids in 54,5% of the strains. Of the tested strains, 91% showed positive signal in the hybridization assays. CONCLUSION: A gene codifying for one specific aminoglycoside-modifying enzyme was detected all throughout the three decades. Our data back the adoption of preventive measures, such as a more conscious use of antimicrobial agents in hospital environments, which can contribute to control the dissemination of microorganisms harboring resistance gene plasmids. PMID- 26148041 TI - Xpert MTB/RIF test performance assay in respiratory samples at real work settings in a developing country. AB - INTRODUCTION: The Xpert MTB/RIF test detects DNA from Mycobacterium tuberculosis complex and susceptibility to rifampin. It has been evaluated repeatedly under "ideal" conditions including centrifugation of sputum and bronchoalveolar lavage, Ziehl Neelsen (ZN) and auramine/rhodamine staining, as well as with solid and liquid automated culture methods. Results from such evaluations cannot be extrapolated to low-income countries that do not routinely use all these processes. OBJECTIVE: To assess the performance of the Xpert MTB/RIF test in respiratory samples under "real" conditions of work in a low-income country and its correlation with phenotypic susceptibility testing. MATERIALS AND METHODS: We conducted a cross-sectional study to assess the performance of the Xpert MTB/RIF test in =12 year-old patients with suspected pulmonary tuberculosis. In routine sample processing at the Hospital we do not use sputum centrifugation, staining with auramine/rhodamine or automated liquid culture. RESULTS: We screened 152 patients of whom 108 were eligible for the study and 103 were included in the analysis; 34% of the samples were positive. The overall test sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 91%, 92%, 83% and 96%, respectively. In ZN-negative samples the sensitivity, specificity, PPV and NPV were 87%, 91%, 68% and 97%, respectively. The results of sensitivity and resistance to rifampin were concordant with susceptibility testing using the multiple proportions method (kappa=1, p<0.0001). CONCLUSIONS: The Xpert MTB/RIF test overall performance was similar to the one achieved under ideal conditions. Its performance in ZN-negative samples was better under "real" conditions of work in a low-income country. PMID- 26148042 TI - [Dengue infection: A common cause of febrile syndrome in patients from Quibdo, Choco, Colombia]. AB - INTRODUCTION: Quibdo, a municipality in Choco, has poor public services and weather and social conditions that favor dengue transmission. However, there are few studies about this problem in this district. OBJECTIVE: To determine the frequency of dengue infection in patients with acute febrile syndrome and to compare clinical features among dengue infected patients with other febrile diseases. MATERIALS AND METHODS: A cross-sectional study was conducted from January, 2008, to March, 2010. The study population comprised patients with febrile syndrome of seven or fewer days of evolution, recruited from hospitals in the town. Dengue diagnosis was made in serum samples by detection of IgM antibodies, NS1 antigen, reverse transcription polymerase chain reaction, and virus isolation. Clinical and laboratory information from the patients was obtained. RESULTS: During the study period, 469 patients with acute febrile syndrome were recruited, of whom 98.3% were Afro-descendant. Dengue fever was found in 28.4% of the cases. Four dengue serotypes were identified with DENV-1 predominance. The ages ranged from zero to 76 years. From all patients, 70.7% of cases were classified as dengue without warning signs. Nausea, vomiting, abdominal pain, cough, nasal congestion and sore throat were significantly more frequent in patients with another febrile disease. CONCLUSIONS: Active surveillance of the acute febrile syndrome allowed for the detection of undiagnosed cases of dengue; the observed frequency of this infection suggests that the study area has a high risk of dengue infection. PMID- 26148043 TI - Phenotypic and genotypic characterization of Neisseria meningitidis serogroup B isolates from Cartagena, Colombia, 2012-2014. AB - INTRODUCTION: Neisseria meningitidis is one of the leading causes of bacterial meningitis. In 2013, an increase in invasive disease caused by N. meningitidis serogroup B occurred in Cartagena, Colombia. OBJECTIVE: The aim of this study was to characterize serogroup B isolates recovered from patients with meningococcal meningitis in Cartagena during 2012 and 2014. MATERIALS AND METHODS: Twenty-five isolates were collected through a national, laboratory-based surveillance, and phenotypic and genotypic characteristics were determined by serosubtyping, serotyping, antimicrobial susceptibility testing, repetitive sequence-based PCR (rep-PCR). MLST data available were also used. RESULTS: The B:10,15:nt phenotype, associated with clonal complex ST-41/44, was responsible for 68.0% of all cases. CONCLUSION: The clinical, epidemiological and molecular characterization of meningococcal disease is necessary for understanding the spread of virulent meningococcal clones and for facilitating the early detection of cases to reduce epidemic risks. PMID- 26148044 TI - [Letters to the editor]. PMID- 26148045 TI - [Letters to the editor]. PMID- 26148046 TI - [Letters to the editor]. PMID- 26148047 TI - The Utility of Including the Strengths of Underage Drinking Laws in Determining Their Effect on Outcomes. AB - BACKGROUND: To control underage drinking in the United States, which has been associated with an estimated 5,000 deaths and 2.6 million injuries or other harm annually, each state has developed a unique set of laws. Previous research examining these laws' effectiveness has frequently focused on the laws' existence without considering variance in sanctions, enforcement, or exemptions. METHODS: We scored 20 minimum legal drinking age 21 (MLDA-21) laws for their strengths and weaknesses based on (i) sanctions for violating the law, (ii) exceptions or exemptions affecting application, and (iii) provisions affecting the law or enforcement. We then replicated a 2009 study of the effects of 6 MLDA-21 laws in 3 different ways (using identical structural equation modeling): Study 1-8 additional years of data, no law strengths; Study 2-years from the original study, added law strengths; Study 3-additional years, law strengths, serving as an update of the 6 laws' effects. RESULTS: In all 3 studies-and the original study-keg registration laws were associated with both an unexpected significant increase (+11%, p < 0.001) in underage drinking-driver ratios and a notable 25% reduction in per capita beer consumption-opposing results that are difficult to explain. In Study 3, possession and purchase laws were associated with a significant decrease in underage drinking-driver fatal crash ratios (-4.9%, p < 0.001; -3.6%, p < 0.001, respectively). Similarly, zero tolerance and use and lose laws were associated with reductions in underage drinking-driver ratios ( 2.8%, p < 0.001; -5.3%, p < 0.001, respectively). CONCLUSIONS: Including strengths and weaknesses of underage drinking laws is important when examining their effects on various outcomes as the model fit statistics indicated. We suggest that this will result in more accurate and more reliable estimates of the impact of the laws on various outcome measures. PMID- 26148050 TI - Hypoxia dose painting in prostate and cervix cancer. PMID- 26148048 TI - Recognition of microbial glycans by human intelectin-1. AB - The glycans displayed on mammalian cells can differ markedly from those on microbes. Such differences could, in principle, be 'read' by carbohydrate-binding proteins, or lectins. We used glycan microarrays to show that human intelectin-1 (hIntL-1) does not bind known human glycan epitopes but does interact with multiple glycan epitopes found exclusively on microbes: beta-linked D galactofuranose (beta-Galf), D-phosphoglycerol-modified glycans, heptoses, D glycero-D-talo-oct-2-ulosonic acid (KO) and 3-deoxy-D-manno-oct-2-ulosonic acid (KDO). The 1.6-A-resolution crystal structure of hIntL-1 complexed with beta-Galf revealed that hIntL-1 uses a bound calcium ion to coordinate terminal exocyclic 1,2-diols. N-acetylneuraminic acid (Neu5Ac), a sialic acid widespread in human glycans, has an exocyclic 1,2-diol but does not bind hIntL-1, probably owing to unfavorable steric and electronic effects. hIntL-1 marks only Streptococcus pneumoniae serotypes that display surface glycans with terminal 1,2-diol groups. This ligand selectivity suggests that hIntL-1 functions in microbial surveillance. PMID- 26148049 TI - Structural basis for the RING-catalyzed synthesis of K63-linked ubiquitin chains. AB - RING E3 ligase-catalyzed formation of K63-linked ubiquitin chains by the Ube2V2 Ubc13 E2 complex is required in many important biological processes. Here we report the structure of the RING-domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with K63 in a position favorable for attack on the linkage between Ubc13 and the donor (second) ubiquitin held in the active 'folded back' conformation by the RING domain of RNF4. We verified the interfaces identified in the structure by in vitro ubiquitination assays of site-directed mutants. To our knowledge, this represents the first view of synthesis of K63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase-mediated catalysis. PMID- 26148051 TI - Unique muscularity in cyclists' thigh and trunk: A cross-sectional and longitudinal study. AB - This study examined the influence of regular training in competitive cycling on individual muscle volume of the thigh and psoas major cross-sectionally and longitudinally. T1-weighted magnetic resonance (MR) images of the trunk and right thigh were obtained from eight experienced varsity male cyclists (experience: > 4 years) and 10 untrained men (experiment 1), and from 12 (10 males, two females) varsity cyclists before and after competitive cycling training for 6 months (experiment 2). From the MR images, the volumes of each of the quadriceps femoris and hamstrings, total adductors, gracilis, sartorius, and psoas major were determined. The volumes of the monoarticular thigh muscles, semitendinosus, and psoas major muscles were significantly greater in the experienced cyclists than in the untrained men (experiment 1), and increased significantly after the competitive training for 6 months (experiment 2). In contrast, the volumes of the other biarticular thigh muscles were similar among the experienced cyclists and untrained men (experiment 1), and did not change by competitive cycling training (experiment 2). The results indicate that competitive cycling training induces muscle-specific hypertrophy of the synergistic muscles, especially between the monoarticular and biarticular muscles, leading to quantitative profiles of the musculature in experienced cyclists. PMID- 26148053 TI - Decadal Declines of Mercury in Adult Bluefish (1972-2011) from the Mid-Atlantic Coast of the U.S.A. AB - Concentrations of total mercury were measured in muscle of adult bluefish (Pomatomus saltatrix) collected in 2011 off North Carolina and compared with similar measurements made in 1972. Concentrations of mercury decreased by 43% in the fish between the two time periods, with an average rate of decline of about 10% per decade. This reduction is similar to estimated reductions of mercury observed in atmospheric deposition, riverine input, seawater, freshwater lakes, and freshwater fish across northern North America. Eight other studies between 1973 and 2007 confirm the decrease in mercury levels in bluefish captured in the Mid-Atlantic Bight. These findings imply that (1) reductions in the release of mercury across northern North America were reflected rather quickly (decades) in the decline of mercury in adult bluefish; (2) marine predatory fish may have been contaminated by anthropogenic sources of mercury for over 100 years; and (3) if bluefish are surrogates for other predators in the Mid-Atlantic Bight, then a reduction in the intake of mercury by the fish-consuming public has occurred. Finally, with global emissions of mercury continuing to increase, especially from Asia, it is important that long-term monitoring programs be conducted for mercury in marine fish of economic importance. PMID- 26148052 TI - Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks. AB - BACKGROUND: Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg remains a potential threat in blood safety. We investigated the actual prevalence, viral factors and genotype of OBI infections in Nigerian blood donors. METHODS: Serum collected from two blood banks were reconfirmed as HBsAg seronegative by ELISA. Forty HBsAg positive samples were employed as controls. HBV-DNA was amplified from all donors and viral loads were determined using quantitative real-time PCR. Antibodies to the HBV core, surface and HBe antigen (anti-HBc,anti-HBs,HBeAg) were measured. The PreS/S and PreC/C regions of the HBV genome were sequenced. RESULTS: Of the 429 blood donors, 72(17%) were confirmed as OBI by DNA detection in different reference labs and excluded the concern of possible contamination. Of the 72 OBI samples, 48(67%) were positive for anti-HBc, 25(35%) positive for anti-HBs, and 2(3%) positive for HBeAg. Of the 72 OBI samples, 31(43%) were seropositive for either anti-HBc, anti-HBs or HBeAg, 21 (30%) positive for both anti-HBc and anti-HBs,one positive for both anti-HBc and HBeAg. None of the OBI samples were positive for all three serological markers. The viral load was <50copies/ml in the OBI samples and genotype E was predominant. The L217R polymorphism in the reverse transcriptase domain of the HBV polymerase gene was observed significantly higher in OBI compared with HBsAg positive individuals (P<0.0001). CONCLUSION: High incidence of OBI is relevant in high endemic areas worldwide and is a general burden in blood safety. This study signifies the high prevalence of OBI and proposes blood donor samples in Nigeria should be pre-tested for OBI by nucleic acid testing (NAT) and/or anti-HBc prior to transfusion to minimize the HBV infection risk. PMID- 26148054 TI - The yield of monitoring for HSV and VZV viremia in pediatric hematopoietic stem cell transplant patients. AB - Reactivation of HSV and VZV is common following HSCT. Consensus guidelines do not support the use of routine screening for viremia following HSCT in adults, but no such clear guidelines exist in pediatrics. In our center, routine practice was to screen patients weekly for HSV and VZV viremia until engraftment in autologous transplant patients and up to day +100 in allogeneic transplant patients. We conducted a retrospective study of over 500 patients to establish whether this screening identified any patients with HSV or VZV viremia who would not have been identified by clinical signs or symptoms. Over a 4.5-yr period, routine screening identified three cases of HSV viremia and one case of VZV viremia. Two patients had persistent, unexplained fever and two patients had skin or mucosal lesions suggestive of HSV/VZV. We conclude that routine screening for HSV and VZV viremia in pediatric HSCT patients has a very low yield and that viremia can be reliably identified by targeted testing in patients with vesicular skin lesions, oral or genital ulceration, unexplained fever, neurological symptoms, or unexplained abnormal liver transaminases. PMID- 26148055 TI - The Impact of Genetic Relationship and Linkage Disequilibrium on Genomic Selection. AB - Genomic selection is a promising research area due to its practical application in breeding. In this study, impact of realized genetic relationship and linkage disequilibrium (LD) on marker density and training population size required was investigated and their impact on practical application was further discussed. This study is based on experimental data of two populations derived from the same two founder lines (B73, Mo17). Two populations were genotyped with different marker sets at different density: IBM Syn4 and IBM Syn10. A high-density marker set in Syn10 was imputed into the Syn4 population with low marker density. Seven different prediction scenarios were carried out with a random regression best linear unbiased prediction (RR-BLUP) model. The result showed that the closer the real genetic relationship between training and validation population, the fewer markers were required to reach a good prediction accuracy. Taken the short-term cost for consideration, relationship information is more valuable than LD information. Meanwhile, the result indicated that accuracies based on high LD between QTL and markers were more stable over generations, thus LD information would provide more robust prediction capacity in practical applications. PMID- 26148056 TI - Hepatitis B Virus Infection Rate and Distribution in Chinese Systemic Lupus Erythematosus Patients. AB - BACKGROUND: The aim of this study was to investigate the hepatitis B virus (HBV) infection rate in systemic lupus erythematosus (SLE) patients in China, and to determine the age and sex distribution. MATERIAL AND METHODS: A total of 3981 SLE patients diagnosed in The First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2011 were retrospectively investigated for evaluation of the HBV infection rate. The HBV infection rate and the positive rate of hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) were standardized to national census data in 2000 and compared with the prevalence found in the 2006 national survey. RESULTS: The age and sex standardized HBV infection rate in Chinese SLE patients was 3.3%. The age and sex standardized positive rate of HBsAb and HBcAb were 58.1% and 26.1%, respectively. As compared with the prevalence from the 2006 national survey, the HBV infection rate and the positive rate of HBcAb were lower and the positive rate of HBsAb was higher in SLE patients aged 15-49 years old compared to peers in the general population. There was no difference in HBV infection rate between males and females (4.2% vs. 2.8%, p=0.088) in SLE patients. CONCLUSIONS: The HBV infection rate was relatively lower in SLE patients compared with the general population, but there was no difference in pediatric patients or patients aged above 50 years old. Unlike in the general population, the HBV infection rate had no statistical differences between males and females in SLE patients. PMID- 26148057 TI - The genetics of human running: ACTN3 polymorphism as an evolutionary tool improving the energy economy during locomotion. AB - BACKGROUND: Covering long distances was an important trait to human evolution and continues to be highlighted for health and athletic status. This ability is benefitted by a low cost of locomotion (CoL), meaning that the individuals who are able to expend less energy would be able to cover longer distances. The CoL has been shown to be influenced by distinct and even 'opposite' factors, such as physiological and muscular characteristics, which are genetically inherited. In this way, DNA alterations could be important determinants of the characteristics associated with the CoL. A polymorphism in the ACTN3 gene (R577X) has been related to physical performance, associating the X allele with endurance and the R allele with strength/power abilities. AIM: To investigate the influence of ACTN3 genotypes on the CoL. SUBJECTS AND METHODS: One hundred and fifty healthy male individuals performed two constant speed tests (at 10 and 12 km/h) to determine the CoL. RESULTS: Interestingly, the results showed that heterozygous individuals (RX genotype) presented significantly lower CoL compared to RR and XX individuals. CONCLUSIONS: It is argued that RX genotype might generate an intermediate strength-to-endurance phenotype, leading to a better phenotypic profile for energy economy during running and, consequently, for long-term locomotion. PMID- 26148058 TI - Allostatic load differs by sex and diet, but not age in older Japanese from the Goto Islands. AB - BACKGROUND: Lifelong exposure to stressors promotes physiological dysregulation and produces an allostatic load (AL). In European-derived samples, AL associates significantly with sex, age and health. AIM: To assess associations of AL with age, sex, socio-demographic differences and self-reports of diet and ability to complete activities of daily living in older Japanese residing in rural Nagasaki Prefecture. SUBJECTS AND METHODS: In 2011, 96 older residents of Nagasaki Prefecture, Japan, were assessed for components of AL. They also self-reported their age, principal life-long occupational activity, educational attainments, marital status, dietary choices and abilities to complete daily living activities. RESULTS: Average age was 67.9 years (range = 55-89; SD = 8.65). Among these 48 men and 48 women, AL was not related significantly to age, although women showed lower AL than men. AL did not differ significantly between respondents by occupation, marital status, education or abilities to complete daily activities. Women who reported eating more green/yellow vegetables or consuming more meat had lower AL than their counterparts. Men who reported drinking more alcohol spirits had higher AL. CONCLUSIONS: Among older Japanese residing outside a major urban area, AL varies significantly by sex, but not age, while being associated with dietary choices. Although lack of association with life ways was not expected, AL apparently assesses physiological dysregulation cross-culturally. PMID- 26148059 TI - Foot Morphological Difference between Habitually Shod and Unshod Runners. AB - Foot morphology and function has received increasing attention from both biomechanics researchers and footwear manufacturers. In this study, 168 habitually unshod runners (90 males whose age, weight & height were 23+/-2.4 years, 66+/-7.1 kg & 1.68+/-0.13 m and 78 females whose age, weight & height were 22+/-1.8 years, 55+/-4.7 kg & 1.6+/-0.11 m) (Indians) and 196 shod runners (130 males whose age, weight & height were 24+/-2.6 years, 66+/-8.2 kg & 1.72+/-0.18 m and 66 females whose age, weight & height were 23+/-1.5 years, 54+/-5.6 kg & 1.62+/-0.15 m) (Chinese) participated in a foot scanning test using the easy-foot scan (a three-dimensional foot scanning system) to obtain 3D foot surface data and 2D footprint imaging. Foot length, foot width, hallux angle and minimal distance from hallux to second toe were calculated to analyze foot morphological differences. This study found that significant differences exist between groups (shod Chinese and unshod Indians) for foot length (female p = 0.001), width (female p = 0.001), hallux angle (male and female p = 0.001) and the minimal distance (male and female p = 0.001) from hallux to second toe. This study suggests that significant differences in morphology between different ethnicities could be considered for future investigation of locomotion biomechanics characteristics between ethnicities and inform last shape and design so as to reduce injury risks and poor performance from mal-fit shoes. PMID- 26148060 TI - The diagnostic value of ultrasonography with 5-15-MHz probes in benign subcutaneous lesions. AB - BACKGROUND: Ultrasonography (US) has recently proved to be useful in diagnostic dermatology. It is convenient to use, completely safe, and provides valuable information. OBJECTIVE: This study was performed to compare the diagnostic accuracy of US with that of clinical diagnosis in patients with benign subcutaneous lesions. METHODS: We retrospectively examined data for 100 patients with benign subcutaneous lesions who were diagnosed with US and either biopsy or surgery at Seoul National University Boramae Hospital between January 2010 and May 2013. RESULTS: Ultrasonography significantly increased the diagnostic yield of benign subcuta-neous lesions (after physical examination [PE], 52.0%; after US, 82.0%; P < 0.005). Rates of sensitivity and specificity for the diagnosis of lipoma were 61.5 and 92.0%, respectively, after PE, and 100 and 100%, respectively, after US. Rates of sensitivity and specificity for the diagnosis of epidermal cysts were 69.4 and 78.4%, respectively, after PE, and 91.8 and 92.2%, respectively, after US. Additionally, rates of sensitivity and specificity for pilomatrixoma were 12.5 and 98.9%, respectively, after PE, and 75.0 and 100%, respectively, after US. Although the accuracy of diagnosis of vascular anomalies and nerve sheath tumors was increased after US, the difference was not significant (vascular anomalies: 40.0% after PE and 80.0% after US; nerve sheath tumors: 28.6% after PE and 42.9% after US). CONCLUSIONS: This study suggests that US is a simple and reliable tool that can aid the diagnosis of benign subcutaneous lesions. PMID- 26148061 TI - Structural Insights Reveal the Dynamics of the Repeating r(CAG) Transcript Found in Huntington's Disease (HD) and Spinocerebellar Ataxias (SCAs). AB - In humans, neurodegenerative disorders such as Huntington's disease (HD) and many spinocerebellar ataxias (SCAs) have been found to be associated with CAG trinucleotide repeat expansion. An important RNA-mediated mechanism that causes these diseases involves the binding of the splicing regulator protein MBNL1 (Muscleblind-like 1 protein) to expanded r(CAG) repeats. Moreover, mutant huntingtin protein translated from expanded r(CAG) also yields toxic effects. To discern the role of mutant RNA in these diseases, it is essential to gather information about its structure. Detailed insight into the different structures and conformations adopted by these mutant transcripts is vital for developing therapeutics targeting them. Here, we report the crystal structure of an RNA model with a r(CAG) motif, which is complemented by an NMR-based solution structure obtained from restrained Molecular Dynamics (rMD) simulation studies. Crystal structure data of the RNA model resolved at 2.3 A reveals non-canonical pairing of adenine in 5'-CAG/3'-GAC motif samples in different syn and anti conformations. The overall RNA structure has helical parameters intermediate to the A- and B-forms of nucleic acids due to the global widening of major grooves and base-pair preferences near internal AA loops. The comprehension of structural behaviour by studying the spectral features and the dynamics also supports the flexible nature of the r(CAG) motif. PMID- 26148062 TI - Network Modeling for Functional Magnetic Resonance Imaging (fMRI) Signals during Ultra-Fast Speech Comprehension in Late-Blind Listeners. AB - In many functional magnetic resonance imaging (fMRI) studies blind humans were found to show cross-modal reorganization engaging the visual system in non-visual tasks. For example, blind people can manage to understand (synthetic) spoken language at very high speaking rates up to ca. 20 syllables/s (syl/s). FMRI data showed that hemodynamic activation within right-hemispheric primary visual cortex (V1), bilateral pulvinar (Pv), and left-hemispheric supplementary motor area (pre SMA) covaried with their capability of ultra-fast speech (16 syllables/s) comprehension. It has been suggested that right V1 plays an important role with respect to the perception of ultra-fast speech features, particularly the detection of syllable onsets. Furthermore, left pre-SMA seems to be an interface between these syllabic representations and the frontal speech processing and working memory network. So far, little is known about the networks linking V1 to Pv, auditory cortex (A1), and (mesio-) frontal areas. Dynamic causal modeling (DCM) was applied to investigate (i) the input structure from A1 and Pv toward right V1 and (ii) output from right V1 and A1 to left pre-SMA. As concerns the input Pv was significantly connected to V1, in addition to A1, in blind participants, but not in sighted controls. Regarding the output V1 was significantly connected to pre-SMA in blind individuals, and the strength of V1 SMA connectivity correlated with the performance of ultra-fast speech comprehension. By contrast, in sighted controls, not understanding ultra-fast speech, pre-SMA did neither receive input from A1 nor V1. Taken together, right V1 might facilitate the "parsing" of the ultra-fast speech stream in blind subjects by receiving subcortical auditory input via the Pv (= secondary visual pathway) and transmitting this information toward contralateral pre-SMA. PMID- 26148063 TI - Timing of Antibiotic Prophylaxis in Elective Caesarean Delivery: A Multi-Center Randomized Controlled Trial and Meta-Analysis. AB - OBJECTIVE: To compare the effectiveness of antibiotic prophylaxis before skin incision with that after umbilical cord clamping in elective caesarean delivery. METHODS: We conducted a randomized open-label controlled trial with two parallel arms at three hospitals in western China. Participants meeting the inclusion criteria received antibiotics 30-60 minutes before skin incision while others received antibiotics after umbilical cords clamping. For the meta-analysis, studies were identified from the database of PUBMED, Cochrane Library and EMbase and assessed using the Cochrane risk of bias tool. RESULTS: Four hundred and ten patients were randomized to receive antibiotics before skin incision (n = 205) or after umbilical cords clamping (n = 205). There was no difference in the incidence of postpartum endometritis (RR = 0.34, 95% CI 0.04 to 3.24), wound infection (RR = 3.06, 95% CI 0.13 to 74.69) and total puerperal morbidity (RR = 1.02, 95% CI 0.47 to 2.22). No increase in the incidence of neonatal sepsis (RR = 0.34, 95% CI 0.04 to 3.24), septic workup (RR = 0.41, 95% CI 0.08 to 2.07), or intermediate NICU admission (RR = 0.73, 95% CI 0.24 to 2.26) was observed. The meta-analysis involving nine RCTs showed that no statistically significant difference was found in terms of the risk of postpartum endometritis (RR = 0.73, 95% CI 0.39, 1.36), wound infection (RR = 0.80, 95%CI 0.55, 1.17), or puerperal morbidity (RR = 0.89, 95% CI 0.70, 1.13). No increase in the incidence of neonatal sepsis (RR = 0.65, 95% CI 0.35 to 1.20), septic workup (RR = 0.88, 95% CI 0.50 to 1.54), or intermediate NICU admission (RR = 0.91, 95% CI 0.70 to 1.18) was observed. CONCLUSION: For elective caesarean delivery, the effects of antibiotic prophylaxis before skin incision and after umbilical cord clamping were equal. Both antibiotic prophylaxis before skin incision and that after umbilical cord clamping were recommended for elective caesarean delivery. The outcome of further studies should address both maternal and neonatal infectious morbidity as well as long-term neonatal follow up. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-11001853. PMID- 26148064 TI - Identification, Characterization and Down-Regulation of Cysteine Protease Genes in Tobacco for Use in Recombinant Protein Production. AB - Plants are an attractive host system for pharmaceutical protein production. Many therapeutic proteins have been produced and scaled up in plants at a low cost compared to the conventional microbial and animal-based systems. The main technical challenge during this process is to produce sufficient levels of recombinant proteins in plants. Low yield is generally caused by proteolytic degradation during expression and downstream processing of recombinant proteins. The yield of human therapeutic interleukin (IL)-10 produced in transgenic tobacco leaves was found to be below the critical level, and may be due to degradation by tobacco proteases. Here, we identified a total of 60 putative cysteine protease genes (CysP) in tobacco. Based on their predicted expression in leaf tissue, 10 candidate CysPs (CysP1-CysP10) were selected for further characterization. The effect of CysP gene silencing on IL-10 accumulation was examined in tobacco. It was found that the recombinant protein yield in tobacco could be increased by silencing CysP6. Transient expression of CysP6 silencing construct also showed an increase in IL-10 accumulation in comparison to the control. Moreover, CysP6 localizes to the endoplasmic reticulum (ER), suggesting that ER may be the site of IL-10 degradation. Overall results suggest that CysP6 is important in determining the yield of recombinant IL-10 in tobacco leaves. PMID- 26148066 TI - Tunable Protein Stabilization In Vivo Mediated by Shield-1 in Transgenic Medaka. AB - Techniques for conditional gene or protein expression are important tools in developmental biology and in the analysis of physiology and disease. On the protein level, the tunable and reversible expression of proteins can be achieved by the fusion of the protein of interest to a destabilizing domain (DD). In the absence of its specific ligand (Shield-1), the protein is degraded by the proteasome. The DD-Shield system has proven to be an excellent tool to regulate the expression of proteins of interests in mammalian systems but has not been applied in teleosts like the medaka. We present the application of the DD-Shield technique in transgenic medaka and show the ubiquitous conditional expression throughout life. Shield-1 administration to the water leads to concentration dependent induction of a YFP reporter gene in various organs and in spermatogonia at the cellular level. PMID- 26148067 TI - Urinary diversion: tailored solutions for individual patients. AB - PURPOSE OF REVIEW: Various urinary diversions are at disposition for reconstructive surgery after cystectomy. The chosen diversion has a strong impact on patients' life regarding complications and quality of life. The purpose of this review is to summarize the current tendency to adapt surgical solutions to individual needs of the patient. RECENT FINDINGS: Tailored surgery requires that the surgeon has been trained in the handling of all gut segments. Only in this case can he react to anatomical variants, patient comorbidities and oncological circumstances, as well as to the prognosis and the social circumstances of the patient with a tailored diversion. Changing demography and ageing populations with increasing incidence of muscle invasive bladder cancer request new, less invasive methods of urinary diversions. There is little evidence as to which is the best urinary diversion due to a lack of well designed studies. SUMMARY: The ileum conduit is still the most used urinary diversion worldwide. However, there are multiple techniques available to us, which guarantee the safest solution in combination with the highest quality of life for the construction of tailored urinary diversion. PMID- 26148065 TI - Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans. AB - INTRODUCTION: Diverse and multi-factorial processes contribute to the progression of cardiovascular disease. These processes affect cells involved in the development of this disease in varying ways, ultimately leading to atherothrombosis. The goal of our study was to compare the differential effects of specific stimuli--two bacterial infections and a Western diet--on platelet responses in ApoE-/- mice, specifically examining inflammatory function and gene expression. Results from murine studies were verified using platelets from participants of the Framingham Heart Study (FHS; n = 1819 participants). METHODS: Blood and spleen samples were collected at weeks 1 and 9 from ApoE-/- mice infected with Porphyromonas gingivalis or Chlamydia pneumoniae and from mice fed a Western diet for 9 weeks. Transcripts based on data from a Western diet in ApoE /- mice were measured in platelet samples from FHS using high throughput qRT-PCR. RESULTS: At week 1, both bacterial infections increased circulating platelet neutrophil aggregates. At week 9, these cells individually localized to the spleen, while Western diet resulted in increased platelet-neutrophil aggregates in the spleen only. Microarray analysis of platelet RNA from infected or Western diet-fed mice at week 1 and 9 showed differential profiles. Genes, such as Serpina1a, Ttr, Fgg, Rpl21, and Alb, were uniquely affected by infection and diet. Results were reinforced in platelets obtained from participants of the FHS. CONCLUSION: Using both human studies and animal models, results demonstrate that variable sources of inflammatory stimuli have the ability to influence the platelet phenotype in distinct ways, indicative of the diverse function of platelets in thrombosis, hemostasis, and immunity. PMID- 26148068 TI - The role of rechallenge with targeted therapies in metastatic renal-cell carcinoma. AB - PURPOSE OF REVIEW: To explore the accumulating evidence and feasibility of rechallenge with agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways for incorporation into the evolving management algorithm for metastatic renal-cell carcinoma (mRCC). RECENT FINDINGS: The current standard of care after the development of resistance to first-line targeted therapies in mRCC is sequential treatment with subsequent lines of alternative anti-VEGF agents or mTOR inhibitors, with optimal sequencing being the focus of ongoing research. Recent evidence from case study and retrospective reports suggests that mRCC patients can achieve important clinical benefits from rechallenge at later lines of therapy with the same targeted therapy used for previous line treatment. Further, the results of REchallenge with SUnitinib in MEtastatic, the first study of sunitinib rechallenge to include a prospective component, reinforce the potential for prolonged survival with this treatment approach for mRCC patients. SUMMARY: Rechallenge represents an important and feasible therapeutic option for the future treatment of mRCC patients. The results of ongoing prospective studies are expected to further evaluate the benefits of rechallenge and better inform wherein this approach fits in the treatment algorithm for mRCC. PMID- 26148069 TI - First-line treatment of metastatic renal cell carcinoma after COMPARZ and PISCES. AB - PURPOSE OF REVIEW: In patients with metastatic renal cell carcinoma and favourable or intermediate risk, sunitinib, pazopanib, and bevacizumab along with interferon have been recommended with identical evidence level I, recommendation grade A. In clinical practice, most physicians and patients are likely to favour an oral treatment (i.e., sunitinib or pazopanib). Choosing between those two tyrosine kinase inhibitors may prove challenging. Two randomized trials have been conducted to facilitate treatment choices, COMPARZ, and PISCES. We discuss below the design of these trials, their results, their potential interpretation, and their clinical implications for selecting treatment. RECENT FINDINGS: Both trials were reported to meet the primary endpoint (i.e., noninferiority of pazopanib versus sunitinib) and patient's preference of pazopanib over sunitinib. However, several methodological aspects have raised doubts about the reliability of these conclusions. Pitfalls include the patients selected for the final analysis, discrepancies of results between the per protocol and intention-to-treat populations, the time points at which quality of life and disease were assessed. SUMMARY: A rigorous head-to-head comparison of pazopanib versus sunitinib is yet to be performed. Clinical considerations and physicans' experience, rather than the reported results of these trials, may continue to influence treatment choices. PMID- 26148070 TI - Oncogenic Role of miR-15a-3p in 13q Amplicon-Driven Colorectal Adenoma-to Carcinoma Progression. AB - Progression from colorectal adenoma to carcinoma is strongly associated with an accumulation of genomic alterations, including gain of chromosome 13. This gain affects the whole q arm and is present in 40%-60% of all colorectal cancers (CRCs). Several genes located at this amplicon are known to be overexpressed in carcinomas due to copy number dosage. A subset of these genes, including the mir 17~92 cluster, are functionally involved in CRC development. The present study set out to explore whether apart from mir-17~92, other miRNAs located at the 13q amplicon show a copy number dependent dosage effect that may contribute to 13q driven colorectal adenoma-to-carcinoma progression. Integration of publically available miRNA expression, target mRNA expression and DNA copy number data from 125 CRCs yielded three miRNAs, miR-15a, -17, and -20a, of which high expression levels were significantly correlated with a 13q gain and which influenced target mRNA expression. These results could be confirmed by qRT-PCR in a series of 100 colon adenomas and carcinomas.Functional analysis of both mature miRNAs encoded by mir-15a, i.e. miR-15a-5p and miR-15a-3p, showed that silencing of miR-15a-3p significantly inhibited viability of CRC cells. Integration of miR-15a expression levels with mRNA expression data of predicted target genes identified mitochondrial uncoupling protein 2 (UCP2) and COP9 signalosome subunit 2 (COPS2) as candidates with significantly decreased expression in CRCs with 13q gain. Upon silencing of miR-15a-3p, mRNA expression of both genes increased in CRC cells, supporting miR-15a-3p mediated regulation of UPC2 and COPS2 expression. In conclusion, significant overexpression of miR-15a-3p due to gain of 13q is functionally relevant in CRC, with UCP2 and COPS2 as candidate target genes. Taken together our findings suggest that miR-15a-3p may contribute to adenoma-to carcinoma progression. PMID- 26148072 TI - Do pre-procedural laboratory parameters predict drug-eluting stent restenosis? PMID- 26148071 TI - Exploring Genetic Factors Involved in Huntington Disease Age of Onset: E2F2 as a New Potential Modifier Gene. AB - Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2 dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor. PMID- 26148073 TI - Corrected balloon occlusive diameter to determine device size during percutaneous atrial septal defect closure. AB - OBJECTIVE: The aim of this trial was to investigate the impact of corrected balloon occlusive diameter (cBOD) on successful performance of percutaneous atrial septal defect (ASD) closure. METHODS: The trial comprised 86 patients (60 female, 26 male; mean age 36.5+/-14.3) on whom percutaneous ASD closure was performed. Patients were evaluated using transesophageal echocardiography (TEE). Relation of the defect to surrounding tissues and size of rims was also investigated. Balloon sizing was performed intraoperatively on all patients. Size of device was ascertained according to both durability of rims and whether or not they formed significant indentation, both of which determine cBOD. RESULTS: The ASD closure device was successfully implanted in 84 (97.5%) patients. Mean maximum defect size was 17.4+/-5.9 mm, and mean color flow diameter was 16.8+/ 5.4 mm. Mean maximum defect size at the moment of loss of shunt flow was 18.4+/ 5.9 mm with TEE, and 18.8+/-6.1 mm with fluoroscopy. Mean size of Amplatzer occluder device was 20.0+/-6.5 mm. Device embolization was observed in 2 patients. However, no death occurred during or after the procedure. CONCLUSION: Percutaneous secundum ASD closure is a safe and effective treatment modality in experienced centers. Utilizing corrected balloon occlusive diameter may be of benefit in deciding the size of ASD occluder device. PMID- 26148074 TI - Lymphocytopenia is associated with poor NYHA functional class in chronic heart failure patients with reduced ejection fraction. AB - OBJECTIVE: In heart failure (HF) patients, functional capacity has been demonstrated to be a marker of poor prognosis, independent of left ventricular ejection fraction (EF). Lymphocyte count is currently recognized in certain risk stratification scores for chronic HF, and severe HF is associated with lymphocytopenia. However, no data exists on the association between lymphocyte count and functional capacity in patients with stable HF. This study aimed to assess the relationship between lymphocyte count and New York Heart Association (NYHA) functional capacity in systolic HF outpatients. METHODS: The Turkish Research Team-HF (TREAT-HF) is a network which undertakes multi-center observational studies in HF. Data on 392 HF reduced ejection fraction (HFREF) patients from 8 HF centers are presented here. The patients were divided into two groups and compared: Group 1 comprised stable HFREF patients with mild symptoms (NYHA Class I-II), while Group 2 consisted of patients with NYHA Class III-IV symptoms. RESULTS: Patient mean age was 60+/-14 years. Lymphocyte count was lower in patients with NYHA functional classes III and IV than in patients with NYHA functional classes I and II, (0.9 [0.6-1.5]x1000 versus 1.5 [0.7-2.2]x1000, p<0.001). In multivariate logistic regression analysis, lymphocyte count (OR: 0.602, 95% CI: 0.375-0.967, p=0.036), advanced age, male gender, presence of hypertension, EF, left atrium size, systolic pulmonary artery pressure, neutrophil and basophil counts, creatinine level, and diuretic usage were associated with poor NYHA functional class in systolic HF outpatients. CONCLUSION: The present study demonstrated that in stable HFREF outpatients, lymphocytopenia was strongly associated with poor NYHA function, independent of coronary heart disease risk factors. PMID- 26148075 TI - [Cardiac and respiratory changes in the medium term after lung resection]. AB - OBJECTIVE: The aim of this study was to assess the cardiac and respiratory functions at the 6th postoperative month, in lung cancer patients undergoing segmentectomy/lobectomy or pneumonectomy. METHODS: Thirteen segmentectomy/lobectomy and 5 pneumonectomy patients with lung cancer were consecutively enrolled between April 2012 and February 2014. All patients underwent respiratory function tests and transthoracic echocardiography preoperatively and at 6 months postoperatively. RESULTS: Left ventricular functions were unchanged postoperatively. In the segmentectomy/lobectomy group, there were no changes in right ventricular fractional area change (RVFAC) or tricuspid annular plane systolic excursion (TAPSE). However, TAPSE decreased from 19 (17-21) to 15.5 (14-16) in pneumonectomy patients (p=0.04). RVFAC was 59.5 (58 61) preoperatively and 59 (58-61) at 6 months postoperatively (p=0.049). Neither group showed differences in pulmonary acceleration time or diastolic and systolic eccentricity indices after operation. Tissue Doppler imaging (TDI) revealed no deterioration in left ventricular functions, but right ventricular diastolic functions (tricuspid E'/A') were impaired in both groups. Right ventricular S', showing the systolic function, was slightly decreased in the pneumonectomy group, in addition to a decrease in isovolumic velocity and isovolumic acceleration (IVA). Only IVA was decreased, from 2.33 (1.79-3.14) to 2.17 (1.73-3.01) (p=0.001), in segmentectomy/lobectomy group. CONCLUSION: Segmentectomy/lobectomy should be preferred over pneumonectomy when possible. Tissue Doppler imaging may be routinely used as a part of echocardiographic evaluation in patients with a higher risk of right ventricular dysfunction in order for these patients to be candidates for a closer cardiovascular follow-up. PMID- 26148076 TI - Assessment of efficacy of single dose acetylsalicylic acid over a 24-hour period. AB - OBJECTIVE: Acetylsalicylic acid (ASA) has a half-life of less than 30 minutes in the human body. This study aimed to test whether the effects of a single dose of ASA wane over a 24-hour period due to the daily release of new reactive blood platelets into the bloodstream. METHODS: The study included 30 patients (10 female and 20 male, mean age: 62.8+/-9.0). Each took a single dose of 300 mg enteric coated ASA orally. Platelet aggregation was determined using VerifyNow(r) Aspirin kits immediately prior to intake, and at 12 and 24 hours following intake. Laboratory parameters such as serum CRP and CBC were also examined before ASA intake. Patients were included irrespective of routine ASA and/or clopidogrel use. RESULTS: Aspirin reaction unit (ARU) values were lower than 550 at 24 hours after drug intake in 26 (86.7%) patients. Values lower than 550 indicate therapeutic range of ASA on platelet function. Two (6.7%) patients were found to be responsive to ASA at 12 hours after intake, but unresponsive at 24 hours. Aspirin resistance was found in another 2 (6.7%) patients. CONCLUSION: Although ASA was found to be effective on platelet inhibition over a 24-hour period in most of the patients, there was a considerable number who were resistant to ASA, and who had developed unresponsiveness to ASA by the end of 24 hours. There is evidence in the literature regarding the clinical importance of ASA resistance, but the importance of loss ASA's effectiveness during a day warrants further studies. PMID- 26148077 TI - Prediction of radial artery diameter in candidates for transradial coronary angiography: Is occupation a factor? AB - OBJECTIVE: Transradial approach (TRA) for coronary angiography is a popular alternative approach to transfemoral coronary angiography due to the infrequent occurrence of access site complications such as bleeding, hematoma and pseudoaneursym formation. However, not all patients are suitable for TRA. This study aimed to determine the predictors of radial artery diameter in patients who are candidates for TRA. METHODS: The study included 222 consecutive patients who underwent TRA due to suspected stable coronary artery disease. Radial artery diameter was evaluated prior to the procedure using B-mode ultrasonography. RESULTS: Radial artery diameter was correlated with wrist circumference (r=0.539, p<0.001), height (r=0.258, p<0.001), weight (r=0.237, p<0.001), body mass index (r=0.167, p=0.013), shoe size (r=0.559, p<0.001), and pulse pressure (r=-0.161, p=0.016). The right radial artery was larger in men than in women (2.73+/-0.39 mm vs. 2.15+/-0.35 mm, p<0.001), and smaller in patients with sedentary office work than in physically active outdoor workers (2.42+/-0.45 mm vs. 2.81+/-0.37 mm, p<0.001). Wrist circumference (b=0.044, p<0.001, confidence interval (CI) 95%= 0.025-0.062), shoe size (b=0.075, p=<0.001, CI 95%=0.039-0.112) and occupation (b=0.228, p<0.001, CI 95%=0.138-0.318) were the independent predictors of radial artery diameter in regression analysis. CONCLUSION: In addition to shoe size and wrist circumference, occupation may be an important predictor of radial artery diameter, and it should be evaluated with other clinical parameters in the prediction of radial artery diameter. PMID- 26148078 TI - Do pre-procedural laboratory parameters predict drug-eluting stent restenosis? AB - OBJECTIVE: Drug-eluting stents (DES) have considerably reduced the rates of in stent restenosis (ISR). Several studies reported pre-procedural C-reactive protein (CRP), neutrophil to lymphocyte (N/L) ratio, red cell distribution width (RDW), serum uric acid (UA), and mean platelet volume (MPV) as independent predictors of ISR using bare metal stents. This study investigates whether any laboratory parameter obtained before the coronary stenting procedure is associated with ISR using DES in stable coronary artery disease. METHODS: Three hundred fifteen stents were retrospectively analysed in 285 patients who had undergone coronary stenting and a control coronary angiography within one year of stenting, between January 2012 and April 2014. Pre-procedural complete blood count, biochemistry, and CRP were recorded. Off-line quantitative coronary angiography analysis was performed. RESULTS: Overall restenosis rate was 10.2%. When the stents were analysed with respect to the presence of ISR, the number of diabetics and smokers was higher in the ISR group. CRP levels were significantly higher in the ISR group, but there were no differences in N/L, monocytes, eosinophils, RDW, MPV, UA, and total bilirubin levels. In the univariate regression analysis, DM, CRP, stent length, stent diameter, pre-procedural diameter stenosis, pre-procedural minimal lumen diameter (MLD), post-procedural residual diameter stenosis, post-procedural reference vessel diameter, and post procedural MLD were predictors of ISR. However, multivariate regression analysis identified only DM and post-procedural residual stenosis as independent predictors of ISR. CONCLUSION: Pre-procedural blood parameters do not independently predict ISR in DES, which is mainly determined by the presence of diabetes and post-procedural residual stenosis. PMID- 26148079 TI - Dunbar syndrome as an unusual cause of exercise-induced retrosternal pain. AB - The median arcuate ligament is a fibrous band connecting the left and right diaphragmatic crura across the aortic hiatus at the level of the T12/L1 vertebral bodies. The low insertion point of this ligament causes significant stenosis of the proximal portion of the coeliac artery in a small group of patients, and contributes to ischemic symptoms known as coeliac artery compression syndrome (CACS). It is also referred to as median arcuate ligament syndrome or Dunbar syndrome. Symptoms include especially postprandial epigastric or retrosternal pain, weight loss, nausea, vomiting, diarrhea and reduced appetite. In severe cases, exercise related abdominal pain may be caused by steal phenomenon, whereby blood is shunted to the skin and relevant muscles during exercise. Computed tomographic angiography and mesenteric angiography are the gold standard diagnostic modalities to confirm diagnosis of CACS. Surgical therapy with release of the median arcuate ligament usually is the primary treatment of choice. Here, we present a 46-year-old male CACS patient with postprandial and especially exercise-induced retrosternal pain radiating to the epigastric region, which may be misperceived as a coronary symptom. PMID- 26148080 TI - An unusual complication after permanent pacemaker implantation: Methemoglobinemia. AB - Permanent pacemaker implantation (PPI) is usually a very safe procedure with a low complication risk. It is a relatively straightforward process carried out under local anesthetic. This case report presents an 80-year-old male patient who required a permanent pacemaker due to complete atrioventricular (AV) block, and who developed cyanosis and was diagnosed with methemoglobinemia after the pacemaker insertion procedure, in which the local anesthetic prilocaine was administered. To our knowledge, this is the first case in the literature to describe methemoglobinemia developing after PPI. PMID- 26148081 TI - Right ventricular outflow tract tachycardia after an initial dose of amantadine. AB - Amantadine hydrochloride is an antiviral agent that is also effective in the treatment of Parkinson's disease. In the literature, cardiac arrhythmia is reported in toxic doses of amantadine, but in this paper we report a patient with right ventricular outflow tract (RVOT) tachycardia after an initial dose of amantadine. A 47-year-old female patient was admitted to the emergency department with the complaint of palpitation and dizziness after taking 200 mg amantadine. A 12-lead standard ECG showed wide QRS complex tachycardia with a heart rate of 167/min. The wide QRS complex tachycardia had an inferior axis and left bundle branch block morphology, compatible with RVOT ventricular tachycardia (RVOT-VT). Tachycardia terminated spontaneously and sinus ECG was completely normal. No arrhythmia was inducible at the electrophysiological study. To the best of our knowledge, this is the first case in the literature to describe RVOT-VT after amantadine intake. Amantadine may cause RVOT-VT as well as other cardiac arrhythmias. PMID- 26148082 TI - A challenging case of transvenous lead extraction. AB - A 72-year-old male patient with a 7-year history of cardioverter-defibrillator (ICD) implantation was admitted to our clinic with pocket infection. One year prior to this admission, he had undergone an unsuccessful extraction procedure at another clinic, during which the older broken ICD lead had been left in place and a newer ICD lead implanted via the same pocket. The newer and older leads were extracted by mechanical dilator sheath and needle eye snare respectively. PMID- 26148083 TI - Retrograde recanalisation of popliteal artery occlusion. AB - The increasing prevalence of critical lower limb ischemia is frequently associated with complex tibioperoneal obstructive disease and a high rate of amputation. In this article, we report our recent experience in order to highlight this valuable and underutilised technique, which proved successful in a complicated case where a conventional approach failed. PMID- 26148084 TI - Conservative management of a left ventricle cardiac fibroma in an asymptomatic child patient. AB - Primary cardiac tumors in infancy and childhood are rare and usually benign. Fibroma is the second most common bening cardiac tumor after rhabdomyoma. Surgery is required when fibromas cause ventricular outflow tract obstruction, ventricular dysfunction and life-threatening arrhythmia. This case report describes a 9-year-old asymptomatic male presenting with a giant left ventricular cardiac fibroma who was followed up using conservative treatment. PMID- 26148085 TI - Almanac 2014: congenital heart disease. AB - This Almanac summarises important congenital heart disease articles published between 2012 and 2014 in Heart and other major cardiac journals. It highlights what the authors perceive to be highly relevant articles in the field. While the aim was to provide a comprehensive overview of the area, a focus on certain areas of interest was required. The selection is, therefore, by necessity a subjective one. PMID- 26148086 TI - Case images: Right atrial myxoma causing distortion of interventricular septum in diastole. PMID- 26148087 TI - Case images: A case of Klippel-Feil syndrome with congenital cardiovascular anomalies. PMID- 26148088 TI - Case images: Giant left ventricular metastasis of uterine leiomyosarcoma mimicking acute coronary syndrome. PMID- 26148089 TI - Case images: An elderly patient with atresia of the left main stem. PMID- 26148090 TI - [Case images: Right arcus aorta and Kommerell diverticulum: A rare challenge encountered as a consequence of increaesed left radial artery interventions]. PMID- 26148091 TI - In Vitro Evidence for Immune-Modulatory Properties of Non-Digestible Oligosaccharides: Direct Effect on Human Monocyte Derived Dendritic Cells. AB - Infant formulas containing non-digestible oligosaccharides (NDO) similar to the composition in breast milk or a combination of lactic acid bacteria (LAB) and NDO have been shown to harbor preventive effects towards immune-regulatory disorders. The aim of this study was to investigate the immune-modulatory potential of non digestible short chain galacto- and long chain fructo-oligosaccharides (scGOS/lcFOS) mimicking the natural distribution of oligosaccharides in human breast milk in presence or absence of certain LAB strains in human monocyte derived dendritic cells (MoDC). Immature human MoDC prepared from peripheral blood of healthy non-atopic volunteers were screened in vitro after stimulation with specific scGOS/lcFOS in presence or absence of LAB. IL-10 and IL-12p70 release was analyzed after 24 hours in cell-free supernatants by enzyme-linked immunosorbent assay (ELISA). A luminex-based assay was conducted to assess further cytokine and chemokine release by MoDC. To investigate the resulting T cell response, stimulated MoDC were co-incubated with naive T cells in allogeneic stimulation assays and intracellular Foxp3 expression, as well as immune suppressive capacity was determined. Oligosaccharides did not induce relevant amounts of IL-12p70 production, but did promote IL-10 release by MoDC. Furthermore, scGOS/lcFOS mixtures exerted a significant enhancing effect on LAB induced IL-10 secretion by MoDC while no increase in IL-12p70 production was observed. Blocking toll like receptor (TLR)4 abrogated the increase in IL-10 in both the direct stimulation and the LAB stimulation of MoDC, suggesting that scGOS/lcFOS act via TLR4. Finally, scGOS/lcFOS-treated MoDC were shown to upregulate the number of functional suppressive Foxp3 positive T cells following allogeneic stimulation. Our results indicate anti-inflammatory and direct, microbiota independent, immune-modulatory properties of scGOS/lcFOS mixtures on human MoDC suggesting a possible induction of regulatory T cells (Tregs). The tested combinations of LAB and scGOS/lcFOS might represent a useful dietary ingredient for the maintenance of intestinal homeostasis via the induction of Tregs. PMID- 26148092 TI - Role of Procalcitonin and Interleukin-6 in Predicting Cancer, and Its Progression Independent of Infection. AB - Procalcitonin (PCT) and Interleukin-6 (IL-6) have emerged as biomarkers for different inflammatory conditions. The purpose of the study was to evaluate the role of PCT and IL-6 as biomarkers of cancer and its progression in a large cohort of patients. This cross-sectional study included residual plasma samples collected from cancer patients, and control subjects without cancer. Levels of PCT and IL-6 were determined by Kryptor compact bioanalyzer. We identified 575 febrile cancer patients, 410 non-febrile cancer patients, and 79 non-cancer individuals. The median PCT level was lower in control subjects (0.029 ng/ml) compared to cancer patients with stage I-III disease (0.127 ng/ml) (p<0.0001) and stage IV disease (0.190 ng/ml) (p<0.0001). It was also higher in febrile cancer patients (0.310 ng/ml) compared to non-febrile cancer patients (0.1 ng/ml) (p<0.0001). Median IL-6 level was significantly lower in the control group (0 pg/ml) than in non-febrile cancer patients with stages I-III (7.376 pg/ml) or stage IV (9.635 pg/ml) (p<0.0001). Our results suggest a potential role for PCT and IL-6 in predicting cancer in non-febrile patients. In addition, PCT is useful in detecting progression of cancer and predicting bacteremia or sepsis in febrile cancer patients. PMID- 26148093 TI - In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis. AB - Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day 102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development. PMID- 26148095 TI - Body image mediates negative family climate and deteriorating glycemic control for single adolescents with type 1 diabetes. AB - INTRODUCTION: Glycemic control declines during adolescence, as youth with diabetes struggle with pubertal changes and a changing social world. The present study tests whether body image mediates longitudinal links between family climate and changes in adolescent glycemic control. Mediation was hypothesized for nondating adolescents but not for dating adolescents, because the former are thought to remain more family oriented than the latter. METHOD: Participants were German adolescents with Type 1 diabetes (51 girls, 58 boys; M = 15.84 years, SD = 1.44). Participants reported body image and family climate. Physicians assayed blood HbA1c levels (M = 8.22%, SD = 1.80%) to measure glycemic control. RESULTS: For nondating adolescents, body image mediated associations between family climate and longitudinal changes in glycemic control. Poorer family climate was associated with poorer body image, which predicted deteriorating glycemic control. For dating adolescents, family climate was unassociated with changes in glycemic control. DISCUSSION: Nondating adolescents may look to parents for feedback on body image, which affects how they manage the challenges of diabetes. Parents and practitioners alike should be alert to the fact that family climate continues to be an important determinant of adolescent adjustment, particularly for those who have not moved into romantic relationships. We know that body image matters to adolescents, but for some youth, body image may be the difference between health and serious physical problems. (PsycINFO Database Record PMID- 26148096 TI - Towards expanding the acute care team: Learning how to involve families in care processes. AB - INTRODUCTION: Effective teamwork is known to be important to improving health care outcomes. Current research often highlights teamwork among health care professionals without consideration of approaches to including family as part of the health care team. In this study, the authors assess family and provider openness to expanding the care team to include family participation and introduce the Family Involvement Menu as a tool to facilitate family engagement. METHOD: They collected 37 family surveys and 37 clinician surveys to understand the perception, comfort level, experience, and interest of family and clinicians in including family in the care of the patient. The majority of family reported being interested and comfortable in participating in care (95% and 92%, respectively). RESULTS: The majority of clinicians considered family already to be part of the health care team (92%) though only 16% reported routinely inviting families to participate in direct patient care all the time. Multiple direct patient care activities were identified as promising opportunities for family engagement. Barriers to family engagement reported included the family being scared (19%), uncomfortable (19%), or unwilling (14%) or nurses not having enough time (14%) to involve families. DISCUSSION: Engaging family has the potential to increase nursing availability for other tasks, enhance relationship building, and is an opportunity to introduce early education for family, better preparing them for transition of care and discharge. The Family Involvement Menu supports family engagement and can be a strategy to include family members as part of the health care team. PMID- 26148094 TI - The Influence of Haemoglobin A1c Levels on Platelet Aggregation and Platelet Turnover in Patients with Coronary Artery Disease Treated with Aspirin. AB - BACKGROUND: Hyperglycaemia may attenuate the antiplatelet effect of aspirin and thereby increase the risk of cardiovascular events. We investigated the influence of increased haemoglobin A1c (HbA1c) levels on platelet aggregation and turnover in a large cohort of patients with coronary artery disease (CAD) with type 2 diabetes, prediabetes or no diabetes. METHODS: In this observational study, we included 865 stable CAD patients on 75 mg aspirin as mono-therapy of whom 242 patients had type 2 diabetes and were receiving antidiabetic drugs. Among 623 patients without diabetes, we classified 303 patients with prediabetes (HbA1c >=5.7-6.4% [39-47 mmol/mol]) naive to antidiabetic drugs. Platelet aggregation was evaluated by the Multiplate Analyzer using arachidonic acid and collagen and by the VerifyNow Aspirin. Platelet turnover was evaluated by immature platelets using flow cytometry and platelet activation by soluble P-selectin. RESULTS: CAD patients with type 2 diabetes had higher platelet aggregation (all p-values <0.01), platelet turnover (immature platelet count, p<0.01) and platelet activation (p<0.001) than patients without diabetes. CAD patients with prediabetes had increased platelet aggregation (p = 0.02) and platelet count (p = 0.02) compared with patients without diabetes. Increased levels of HbA1c correlated positively with increased platelet aggregation using arachidonic acid (r = 0.19, p<0.0001), collagen (r = 0.10, p<0.01) and VerifyNow (r = 0.15, p<0.0001), and with platelet count (r = 0.08, p = 0.01), immature platelet count (r = 0.11, p<0.001) and soluble P-selectin (r = 0.15, p<0.0001). These associations were mainly evident in non-diabetic and prediabetic CAD patients. CONCLUSIONS: CAD patients with prediabetes and diabetes may have attenuated antiplatelet effect of aspirin compared with CAD patients without diabetes. This may be related to increased platelet count in patients with prediabetes. Increased levels of HbA1c correlated positively, though weakly, with increased platelet aggregation, platelet turnover and platelet activation. PMID- 26148097 TI - Chorioamniotic membrane separation after fetoscopy in monochorionic twin pregnancy: incidence and impact on perinatal outcome. AB - OBJECTIVE: To evaluate the incidence of chorioamniotic membrane separation (CMS) after fetoscopy in monochorionic diamniotic (MCDA) twins and its impact on pregnancy outcome. METHODS: The study group comprised a consecutive series of 338 women with an MCDA pregnancy complicated by twin-twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR) treated with selective laser photocoagulation of communicating vessels (SLPCV) or cord occlusion (CO). Data obtained included cervical length, gestational age at procedure, type and duration of surgery and placental location. The incidence of CMS, the rates of miscarriage and preterm prelabor rupture of membranes (PPROM), gestational age at delivery and neonatal survival were recorded. RESULTS: Of the study population of MCDA pregnancies, 270 (79.9%) had TTTS and 68 (20.1%) had sIUGR. SLPCV was performed in 252 (74.6%) cases and CO in 86 (25.4%). Postoperative CMS was observed in 70 (20.7%) cases. Patients with CMS had higher rates of miscarriage (14.3% vs 7.1%; P = 0.049), PPROM before 32 weeks (43.3% vs 13.7%; P < 0.001) and preterm delivery before 32 weeks (53.3% vs 26.1%; P < 0.001) and a lower rate of neonatal survival of at least one twin (81.7% vs 93.6%; P = 0.003). Multivariate analysis showed that gestational age at surgery was the only independent predictor, with the highest proportion of CMS occurring in cases that underwent surgery before 18 weeks' gestation (odds ratio, 2.941 (95% CI, 1.640-5.275); P < 0.001). There was no influence of cervical length, placental location, duration of surgery or type of surgery on the risk of CMS. CONCLUSIONS: CMS complicated one-fifth of all MCDA pregnancies that underwent fetoscopy. It appeared to be more common in those who underwent surgery before 18 weeks' gestation and was associated with poorer outcomes. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26148098 TI - Construction, De-Novo Assembly and Analysis of Transcriptome for Identification of Reproduction-Related Genes and Pathways from Rohu, Labeo rohita (Hamilton). AB - Rohu is a leading candidate species for freshwater aquaculture in South-East Asia. Unlike common carp the monsoon breeding habit of rohu restricts its seed production beyond season indicating strong genetic control over spawning. Genetic information is limited in this regard. The problem is exacerbated by the lack of genomic-resources. We identified 182 reproduction-related genes previously by Sanger-sequencing which were less to address the issue of seasonal spawning behaviour of this important carp. Therefore, the present work was taken up to generate transcriptome profile by mRNAseq. 16 GB, 72 bp paired end (PE) data was generated from the pooled-RNA of twelve-tissues from pre-spawning rohu using IlluminaGA-II-platform. There were 64.97 million high-quality reads producing 62,283 contigs and 88,612 numbers of transcripts using velvet and oases programs, respectively. Gene ontology annotation identified 940 reproduction-related genes consisting of 184 mainly associated with reproduction, 223 related to hormone activity and receptor-binding, 178 receptor-activity and 355 embryonic development related-proteins. The important reproduction-relevant pathways found in KEGG analysis were GnRH-signaling, oocyte-meiosis, steroid-biosynthesis, steroid-hormone biosynthesis, progesterone-mediated oocyte-maturation, retinol metabolism, neuroactive-ligand-receptor interaction, neurotrophin-signaling and photo-transduction. Twenty nine simple sequence repeat containing sequences were also found out of which 12 repeat loci were polymorphic with mean expected-& observed heterozygosity of 0.471 and 0.983 respectively. Quantitative RT-PCR analyses of 13-known and 6-unknown transcripts revealed differences in expression level between preparatory and post-spawning phase. These transcriptomic sequences have significantly increased the genetic-&-genomic resources for reproduction research in Labeo rohita. PMID- 26148100 TI - Ketamine Saves the Day: Priapism in a Pediatric Psychiatric Patient. AB - Priapism is an adverse effect of medications used to treat psychiatric disorders. Often, this condition is self-limiting but may require urologic intervention involving aspiration and injection to induce detumescence. A case of a 15-year old patient with priapism secondary to a long-acting stimulant is presented to describe the effectiveness of ketamine treatment for priapism. PMID- 26148099 TI - Excess Mortality in Patients with Multiple Sclerosis Starts at 20 Years from Clinical Onset: Data from a Large-Scale French Observational Study. AB - BACKGROUND: Recent studies in multiple sclerosis (MS) showed longer survival times from clinical onset than older hospital-based series. However estimated median time ranges widely, from 24 to 45 years, which makes huge difference for patients as this neurological disease mainly starts around age 20 to 40. Precise and up-to-date reference data about mortality in MS are crucial for patients and neurologists, but unavailable yet in France. OBJECTIVES: Estimate survival in MS patients and compare mortality with that of the French general population. METHODS: We conducted a multicenter observational study involving clinical longitudinal data from 30,413 eligible patients, linked to the national deaths register. Inclusion criteria were definite MS diagnosis and clinical onset prior to January, 1st 2009 in order to get a minimum of 1-year disease duration. RESULTS: After removing between-center duplicates and applying inclusion criteria, the final population comprised 27,603 MS patients (F/M sex ratio 2.5, mean age at onset 33.0 years, 85.5% relapsing onset). During the follow-up period (mean 15.2 +/- 10.3 years), 1569 deaths (5.7%) were identified; half related to MS. Death rates were significantly higher in men, patients with later clinical onset, and in progressive MS. Overall excess mortality compared with the general population was moderate (Standardized Mortality Ratio 1.48, 95% confidence interval [1.41-1.55]), but increased considerably after 20 years of disease (2.20 [2.10-2.31]). CONCLUSIONS: This study revealed a moderate decrease in life expectancy in MS patients, and showed that the risk of dying is strongly correlated to disease duration and disability, highlighting the need for early actions that can slow disability progression. PMID- 26148101 TI - Liquid Nicotine Toxicity. AB - E-cigarettes, also known as electronic nicotine delivery systems and electronic cigarettes, are advertised as a healthier alternative product to tobacco cigarettes despite limited data on the consequences of e-cigarette use. Currently, there are no US Food and Drug Administration or other federal regulations of e-cigarettes, and calls to poison control centers regarding liquid nicotine toxicity, especially in children, are on the rise. This article presents the background and mechanism of action of e-cigarettes as well as up-to-date details of the toxicity of liquid nicotine. We also present management strategies in the setting of liquid nicotine toxicity. PMID- 26148103 TI - Point-of-Care Ultrasonography by Pediatric Emergency Medicine Physicians. AB - April 2015 marks the publication of the first national guideline regarding point of-care ultrasound by pediatric emergency medicine physicians. The joint statement by the American Academy of Pediatrics, Society for Academic Emergency Medicine, American College of Emergency Physicians, and World Interactive Network Focused on Critical Ultrasound provides a framework on which pediatric emergency physicians can develop the necessary skills to use point-of-care ultrasound effectively and responsibly. PMID- 26148104 TI - The Use of Automated External Defibrillators in Infants: A Report From the American Red Cross Scientific Advisory Council. AB - OBJECTIVE: Automated external defibrillators (AEDs) have been used successfully in many populations to improve survival for out-of-hospital cardiac arrest. While ventricular fibrillation and pulseless ventricular tachycardia are more prevalent in adults, these arrhythmias do occur in infants. The Scientific Advisory Council of the American Red Cross reviewed the literature on the use of AEDs in infants in order to make recommendations on use in the population. METHODS: The Cochrane library and PubMed were searched for studies that included AEDs in infants, any external defibrillation in infants, and simulation studies of algorithms used by AEDs on pediatric arrhythmias. RESULTS: There were 4 studies on the accuracy of AEDs in recognizing pediatric arrhythmias. Case reports (n = 2) demonstrated successful use of AED in infants, and a retrospective review (n = 1) of pediatric pads for AEDs included infants. Six studies addressed defibrillation dosages used. The algorithms used by AEDs had high sensitivity and specificity for pediatric arrhythmias and very rarely recommended a shock inappropriately. The energy doses delivered by AEDs were high, although in the range that have been used in out-of-hospital arrest. In addition, there are data to suggest that 2 to 4 J/kg may not be effective defibrillation doses for many children. CONCLUSIONS: In the absence of prompt defibrillation for ventricular fibrillation or pulseless ventricular tachycardia, survival is unlikely. Automated external defibrillators should be used in infants with suspected cardiac arrest, if a manual defibrillator with a trained rescuer is not immediately available. Automated external defibrillators that attenuate the energy dose (eg, via application of pediatric pads) are recommended for infants. If an AED with pediatric pads is not available, the AED with adult pads should be used. PMID- 26148105 TI - An Uncommon Complication of Sinusitis in a Young Adolescent. AB - A young adolescent patient presented to the emergency department with forehead and eyelid swelling after a week of nasal discharge that was suspicious for Pott's puffy tumor. Point-of-care ultrasound facilitated rapid diagnosis and initiation of treatment for a concerning and rare complication of sinusitis, confirmed by computed tomography scan. PMID- 26148106 TI - Pediatric Emergency Medicine: Legal Briefs. PMID- 26148107 TI - An Introduction to Natural Language Processing: How You Can Get More From Those Electronic Notes You Are Generating. AB - Electronically stored clinical documents may contain both structured data and unstructured data. The use of structured clinical data varies by facility, but clinicians are familiar with coded data such as International Classification of Diseases, Ninth Revision, Systematized Nomenclature of Medicine-Clinical Terms codes, and commonly other data including patient chief complaints or laboratory results. Most electronic health records have much more clinical information stored as unstructured data, for example, clinical narrative such as history of present illness, procedure notes, and clinical decision making are stored as unstructured data. Despite the importance of this information, electronic capture or retrieval of unstructured clinical data has been challenging. The field of natural language processing (NLP) is undergoing rapid development, and existing tools can be successfully used for quality improvement, research, healthcare coding, and even billing compliance. In this brief review, we provide examples of successful uses of NLP using emergency medicine physician visit notes for various projects and the challenges of retrieving specific data and finally present practical methods that can run on a standard personal computer as well as high end state-of-the-art funded processes run by leading NLP informatics researchers. PMID- 26148108 TI - ECGs in the ED. PMID- 26148109 TI - A Case of Hemophagocytic Lymphohistiocytosis and the Uncertainty About the Cause of Takotsubo Syndrome. PMID- 26148110 TI - Left-Without-Being-Seen Rates: Not Useful for Comparison, Just Keep Them Low. PMID- 26148111 TI - Life-Threatening and Rare Adverse Effects of Phenytoin. PMID- 26148113 TI - The Future of Next-Generation Sequencing in Neurology. PMID- 26148112 TI - Functional characterization of mutants affected in the carbonic anhydrase domain of the respiratory complex I in Arabidopsis thaliana. AB - The NADH-ubiquinone oxidoreductase complex (complex I) (EC 1.6.5.3) is the main entrance site of electrons into the respiratory chain. In a variety of eukaryotic organisms, except animals and fungi (Opisthokonta), it contains an extra domain comprising trimers of putative gamma-carbonic anhydrases, named the CA domain, which has been proposed to be essential for assembly of complex I. However, its physiological role in plants is not fully understood. Here, we report that Arabidopsis mutants defective in two CA subunits show an altered photorespiratory phenotype. Mutants grown in ambient air show growth retardation compared to wild type plants, a feature that is reversed by cultivating plants in a high-CO2 atmosphere. Moreover, under photorespiratory conditions, carbon assimilation is diminished and glycine accumulates, suggesting an imbalance with respect to photorespiration. Additionally, transcript levels of specific CA subunits are reduced in plants grown under non-photorespiratory conditions. Taken together, these results suggest that the CA domain of plant complex I contributes to sustaining efficient photosynthesis under ambient (photorespiratory) conditions. PMID- 26148114 TI - Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence. AB - Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH 23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg i.v.), the mean emergence times for rats that received normal saline (vehicle) and dextroamphetamine (1 mg/kg i.v.) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from delta (0.1-4 Hz) to theta (4-8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH 23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes significant neurophysiological changes, but does not promote behavioral arousal during general anesthesia. We hypothesize that dextroamphetamine is more likely than atomoxetine to be clinically useful for restoring consciousness in anesthetized patients, mainly due to its stimulation of dopaminergic neurotransmission. PMID- 26148115 TI - Psychosocial interventions for smoking cessation in patients with coronary heart disease. AB - BACKGROUND: This is an update of a Cochrane review previously published in 2008. Smoking increases the risk of developing atherosclerosis but also acute thrombotic events. Quitting smoking is potentially the most effective secondary prevention measure and improves prognosis after a cardiac event, but more than half of the patients continue to smoke, and improved cessation aids are urgently required. OBJECTIVES: This review aimed to examine the efficacy of psychosocial interventions for smoking cessation in patients with coronary heart disease in short-term (6 to 12 month follow-up) and long-term (more than 12 months). Moderators of treatment effects (i.e. intervention types, treatment dose, methodological criteria) were used for stratification. SEARCH METHODS: The Cochrane Central Register of Controlled Trials (Issue 12, 2012), MEDLINE, EMBASE, PsycINFO and PSYNDEX were searched from the start of the database to January 2013. This is an update of the initial search in 2003. Results were supplemented by cross-checking references, and handsearches in selected journals and systematic reviews. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with CHD with a minimum follow-up of 6 months. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and risk of bias. Abstinence rates were computed according to an intention to treat analysis if possible, or if not according to completer analysis results only. Subgroups of specific intervention strategies were analysed separately. The impact of study quality on efficacy was studied in a moderator analysis. Risk ratios (RR) were pooled using the Mantel-Haenszel and random-effects model with 95% confidence intervals (CI). MAIN RESULTS: We found 40 RCTs meeting inclusion criteria in total (21 trials were new in this update, 5 new trials contributed to long-term results (more than 12 months)). Interventions consist of behavioural therapeutic approaches, telephone support and self-help material and were either focused on smoking cessation alone or addressed several risk factors (eg. obesity, inactivity and smoking). The trials mostly included older male patients with CHD, predominantly myocardial infarction (MI). After an initial selection of studies three trials with implausible large effects of RR > 5 which contributed to substantial heterogeneity were excluded. Overall there was a positive effect of interventions on abstinence after 6 to 12 months (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.13 to 1.32, I2 54%; abstinence rate treatment group = 46%, abstinence rate control group 37.4%), but heterogeneity between trials was substantial. Studies with validated assessment of smoking status at follow-up had similar efficacy (RR 1.22, 95% CI 1.07 to 1.39) to non validated trials (RR 1.23, 95% CI 1.12 to 1.35). Studies were stratified by intervention strategy and intensity of the intervention. Clustering reduced heterogeneity, although many trials used more than one type of intervention. The RRs for different strategies were similar (behavioural therapies RR 1.23, 95% CI 1.12 to 1.34, I2 40%; telephone support RR 1.21, 95% CI 1.12 to 1.30, I2 44%; self-help RR 1.22, 95% CI 1.12 to 1.33, I2 40%). More intense interventions (any initial contact plus follow-up over one month) showed increased quit rates (RR 1.28, 95% CI 1.17 to 1.40, I2 58%) whereas brief interventions (either one single initial contact lasting less than an hour with no follow-up, one or more contacts in total over an hour with no follow-up or any initial contact plus follow-up of less than one months) did not appear effective (RR 1.01, 95% CI 0.91 to 1.12, I2 0%). Seven trials had long-term follow-up (over 12 months), and did not show any benefits. Adverse side effects were not reported in any trial. These findings are based on studies with rather low risk of selection bias but high risk of detection bias (namely unblinded or non validated assessment of smoking status). AUTHORS' CONCLUSIONS: Psychosocial smoking cessation interventions are effective in promoting abstinence up to 1 year, provided they are of sufficient duration. After one year, the studies showed favourable effects of smoking cessation intervention, but more studies including cost-effectiveness analyses are needed. Further studies should also analyse the additional benefit of a psychosocial intervention strategy to pharmacological therapy (e.g. nicotine replacement therapy) compared with pharmacological treatment alone and investigate economic outcomes. PMID- 26148116 TI - Chemical Modification of a Dehydratase Enzyme Involved in Bacterial Virulence by an Ammonium Derivative: Evidence of its Active Site Covalent Adduct. AB - The first example of an ammonium derivative that causes a specific modification of the active site of type I dehydroquinase (DHQ1), a dehydratase enzyme that is a promising target for antivirulence drug discovery, is described. The resolution at 1.35 A of the crystal structure of DHQ1 from Salmonella typhi chemically modified by this ammonium derivative revealed that the ligand is covalently attached to the essential Lys170 through the formation of an amine. The detection by mass spectroscopy of the reaction intermediates, in conjunction with the results of molecular dynamics simulations, allowed us to explain the inhibition mechanism and the experimentally observed differences between S. typhi and Staphylococcus aureus enzymes. The results presented here reveal that the replacement of Phe225 in St-DHQ1 by Tyr214 in Sa-DHQ1 and its hydrogen bonding interaction with the conserved water molecule observed in several crystal structures protects the amino adduct against further dehydration/aromatization reactions. In contrast, for the St-DHQ1 enzyme, the carboxylate group of Asp114, with the assistance of this water molecule, would trigger the formation of a Schiff base that can undergo further dehydration reactions until full aromatization of the cyclohexane ring is achieved. Moreover, in vitro antivirulence studies showed that the reported compound is able to reduce the ability of Salmonella Enteritidis to kill A459 respiratory cells. These studies have identified a good scaffold for the design of irreversible inhibitors that can be used as drugs and has opened up new opportunities for the development of novel antivirulence agents by targeting the DHQ1 enzyme. PMID- 26148117 TI - Comparative Chromosome Painting and NOR Distribution Suggest a Complex Hybrid Origin of Triploid Lepidodactylus lugubris (Gekkonidae). AB - Parthenogenesis, unisexuality and triploidy are interesting but poorly studied phenomena occurring in some reptile species. The mourning gecko (Lepidodactylus lugubris) represents a complex of diploid and triploid parthenogenetic mostly all female populations (males occur quite rarely) widely distributed in coastal areas of the Indian and Pacific Oceans. Here, we study karyotypes of a male and two female L. lugubris (LLU) triploid individuals (3n = 66) using comparative painting with Gekko japonicus, Hemidactylus turcicus and H. platyurus chromosome specific probes to visualize the homologous regions and to reveal genus specific rearrangements. Also, we applied a 28S ribosomal DNA probe and Ag-staining to detect nucleolus organizer regions (NORs). Our results suggest that the karyotype of L. lugubris underwent a chromosome fission and a fusion after its divergence from a common ancestor of the Gekko-Hemidactylus group. The NORs were found to be located on one out of three homologs on each of LLU8, LLU15 and LLU18, thus further confirming a hybrid origin of triploid individuals. It seems that three different bisexual populations might have contributed to the origin of this triploid parthenogenetic population. We postulate that the heterozygosity in NOR localization is maintained in the triploid clone studied by the absence of recombination as described in whiptail lizards. The pattern of NOR localizations and homologous regions in males and females, as well as the absence of other detectable karyotypic differences, suggest that males arise spontaneously in all female populations and do not arise from independent hybridizations with different species. PMID- 26148118 TI - Potentiation of Growth Inhibitory Responses of the mTOR Inhibitor Everolimus by Dual mTORC1/2 Inhibitors in Cultured Breast Cancer Cell Lines. AB - The mammalian target of rapamycin (mTOR), a vital component of signaling pathways involving PI3K/AKT, is an attractive therapeutic target in breast cancer. Everolimus, an allosteric mTOR inhibitor that inhibits the mTOR functional complex mTORC1, is approved for treatment of estrogen receptor positive (ER+) breast cancer. Other mTOR inhibitors show interesting differences in target specificities: BEZ235 and GSK2126458 are ATP competitive mTOR inhibitors targeting both PI3K and mTORC1/2; AZD8055, AZD2014 and KU-0063794 are ATP competitive mTOR inhibitors targeting both mTORC1 and mTORC2; and GDC-0941 is a pan-PI3K inhibitor. We have addressed the question of whether mTOR inhibitors may be more effective in combination than singly in inhibiting the proliferation of breast cancer cells. We selected a panel of 30 human breast cancer cell lines that included ER and PR positive, HER2 over-expressing, and "triple negative" variants, and determined whether signaling pathway utilization was related to drug-induced inhibition of proliferation. A significant correlation (p = 0.005) was found between everolimus IC50 values and p70S6K phosphorylation, but not with AKT or ERK phosphorylation, consistent with the mTOR pathway being a principal target. We then carried out combination studies with four everolimus resistant triple-negative breast cancer cell lines, and found an unexpectedly high degree of synergy between everolimus and the other inhibitors tested. The level of potentiation of everolimus inhibitory activity (measured by IC50 values) was found to be cell line-specific for all the kinase inhibitors tested. The results suggest that judicious combination of mTOR inhibitors with different modes of action could have beneficial effects in the treatment of breast cancer. PMID- 26148119 TI - Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts. AB - OBJECTIVE: Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment. METHODS: We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time. RESULTS: In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003). CONCLUSIONS: Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally. PMID- 26148120 TI - Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings. AB - Previous studies reported that Multiple Sclerosis (MS) patients treated with natalizumab for one or two years exhibit a significant reduction in relapse rate and in cognitive impairment, but the long term effects on cognitive performance are unknown. This study aimed to evaluate the effects of natalizumab on cognitive impairment in a cohort of 24 consecutive patients with relapsing remitting MS treated for 3 years. The neuropsychological tests, as well as relapse number and EDSS, were assessed at baseline and yearly for three years. The impact on cortical atrophy was also considered in a subgroup of them, and are thus to be considered as preliminary. Results showed a significant reduction in the number of impaired neuropsychological tests after three years, a significant decrease in annualized relapse rate at each time points compared to baseline and a stable EDSS. In the neuropsychological assessment, a significant improvement in memory, attention and executive function test scores was detected. Preliminary MRI data show that, while GM volume did not change at 3 years, a significantly greater parahippocampal and prefrontal gray matter density was noticed, the former correlating with neuropsychological improvement in a memory test. This study showed that therapy with Natalizumab is helpful in improving cognitive performance, and is likely to have a protective role on grey matter, over a three years follow-up. PMID- 26148121 TI - Violaceous plaque on the nose referred for rhinophyma surgery. PMID- 26148122 TI - Systemic inflammation and proinflammatory interleukin-17 signalling persist at the end of therapy in patients with metabolic syndrome and psoriasis, reducing the length of remission. PMID- 26148123 TI - An energy-absorbing sliding seat for reducing neck injury risks in rear impact- analysis for prototype built. AB - OBJECTIVE: This study investigated overall performance of an energy-absorbing sliding seat concept for whiplash neck injury prevention. The sliding seat allows its seat pan to slide backward for some distance under certain restraint force to absorb crash energy in rear impacts. METHODS: A numerical model that consisted of vehicle interior, seat, seat belt, and BioRID II dummy was built in MADYMO to evaluate whiplash neck injury in rear impact. A parametric study of the effects of sliding seat parameters, including position and cushion stiffness of head restraint, seatback cushion stiffness, recliner characteristics, and especially sliding energy-absorbing (EA) restraint force, on neck injury criteria was conducted in order to compare the effectiveness of the sliding seat concept with that of other existing anti-whiplash mechanisms. Optimal sliding seat design configurations in rear crashes of different severities were obtained. A sliding seat prototype with bending of a steel strip as an EA mechanism was fabricated and tested in a sled test environment to validate the concept. The performance of the sliding seat under frontal and rollover impacts was checked to make sure the sliding mechanism did not result in any negative effects. RESULTS: The protective effect of the sliding seat with EA restraint force is comparable to that of head restraint-based and recliner stiffness-based anti-whiplash mechanisms. EA restraint force levels of 3 kN in rear impacts of low and medium severities and 6 kN in impacts of high severity were obtained from optimization. In frontal collision and rollover, compared to the nonsliding seat, the sliding seat does not result in any negative effects on occupant protection. The sled test results of the sliding seat prototype have shown the effectiveness of the concept for reducing neck injury risks. CONCLUSION: As a countermeasure, the sliding seat with appropriate restraint forces can significantly reduce whiplash neck injury risk in rear impacts of low, medium, and high severities with no negative effects on other crash load cases. PMID- 26148124 TI - Stigma towards Marijuana Users and Heroin Users. AB - Despite high levels of stigmatizing attitudes and behaviors toward individuals with substance use problems, there is surprisingly limited research on understanding the contributors to such high levels. College students with no history of marijuana or heroin use (N=250) completed self-report measures to examine the level of substance use stigma towards individuals using two illicit substances (marijuana and heroin) and the contribution of three perceiver characteristics (sex, previous contact with substance users, and five beliefs about substance use) to three dimensions of stigma (social distance, negative emotions, and forcing treatment). Greater levels of internalized stigma were noted towards individuals who use heroin (versus marijuana). For marijuana use, those who had less previous contact and higher endorsement of certain beliefs (rarity, severity, and less controllability) were associated with greater stigmatizing attitudes. For heroin use, the associations were weak or non existent. The findings strengthen the argument that substance use stigma needs to be examined and perhaps addressed substance by substance, rather than as a group. Further, contact interventions may be a particularly effective strategy for altering substance use stigma. PMID- 26148125 TI - Psychosocial adaptation: an evolutionary concept analysis exploring a common multidisciplinary language. AB - AIMS: To provide the first known concept analysis of psychosocial adaptation, exploring its evolution from the concept adaptation. We also determine how psychosocial adaptation is conceptualized across nursing, health, sociobehavioural and education disciplines. BACKGROUND: Psychosocial adaptation is an important conceptual term that is poorly defined in nursing and other health, sociobehavioural and education disciplines. A thorough understanding of the concept's application in nursing and across disciplines can help to clarify its meaning, facilitate a more effective common language between disciplines and inform future psychosocial adaptation research. DESIGN: Rodger's evolutionary view guided this concept analysis. DATA SOURCES: Peer-reviewed English and Spanish manuscripts published between 2011-2013 were retrieved from the following databases: CINAHL, Psych INFO, PubMed, Scopus and LILACS. REVIEW METHODS: Eighty nine articles related to psychosocial adaptation were included in the analysis. Findings identify key attributes, antecedents and consequences associated with the use of the concept. Findings were compared vis-a-vis reported characteristics of adaptation. RESULTS: The attributes characterizing psychosocial adaptation are: change, process, continuity, interaction and influence. In psychosocial adaptation, new life conditions serve as antecedents, while consequences are good or bad outcomes. Important features of the evolution of this concept include its broad appropriation across the reviewed disciplines. The attributes of psychosocial adaptation, have some similarities to those of general adaptation. Both concepts include an aspect of change, but unlike adaptation, psychosocial adaptation has branched away from biological descriptors, such as homeostasis and tends to focus on relational characteristics, such as interaction and influences. PMID- 26148126 TI - Rational Design of Cathode Structure for High Rate Performance Lithium-Sulfur Batteries. AB - Practical applications of Li-S batteries require not only high specific capacities and long cycle lifetimes but also high rate performance. We report a rationally designed Li-S cathode, which consists of a freestanding composite thin film assembled from S nanoparticles, reduced graphene oxide (rGO), and a multifunctional additive poly(anthraquinonyl sulfide) (PAQS). The S nanoparticles provide a high initial specific capacity, and the layered and porous rGO structure provides electron and ion transport paths and restricts polysulfide shuttling. PAQS is not only a highly efficient sulfide trapping agent but also an excellent Li(+) conductor, which benefits the battery reaction kinetics at a high rate. The resulting cathode exhibits an initial specific capacity of 1255 mAh g( 1) with a decay rate as low as 0.046% per cycles over 1200 cycles. Importantly, it displays a reversible capacity of 615 mAh g(-1) when discharged at a high rate of 8 C (13.744 A g(-1)). PMID- 26148127 TI - Sexual Concerns of Patients With Implantable Left Ventricular Assist Devices. AB - The growing field of implantable left ventricular assist devices (LVADs) lacks studies that evaluate the sexual and psychosocial concerns of LVAD patients. The aim of this prospective study was to determine the sexual and psychosocial behaviors of these patients. A sexual and psychosocial survey was conducted in patients who underwent the implantation of LVAD. Inclusion criteria were patients who were discharged home. The survey consisted of 17 questions with main focus on the sexual life and activities. The survey was sent to 38 patients. Twelve patients had either no partners or did not respond to the survey. Data of the remaining 26 patients with a mean age of 54 +/- 13 years old were analyzed. The mean time between LVAD implantation and the first sexual activity was 16 +/- 13 weeks (6-42 weeks). Following LVAD implantation, there was a steady improvement in the physical condition and quality of life. However, a remarkable decrease in the degree of satisfaction with sexual life following LVAD implantation (5.5 +/- 2.2 vs. 4.1 +/- 2.5) was observed (P = 0.05) (a scale of 1-7, with 7 being very satisfied and 1 not satisfied). Decreasing sexual activities after LVAD implantation was mainly to avoid partner disappointment, sudden cardiac arrest, and LVAD failure. There is a notable reduction in the degree of satisfaction with sexual life after LVAD implantation. The majority of the patients avoid discussing this issue with their physicians. Psychological and psychosocial support of LVAD patients is mandatory to improve their life quality. PMID- 26148128 TI - An extended version of the theory of planned behaviour: the role of self-efficacy and past behaviour in predicting the physical activity of Chinese adolescents. AB - This study aimed to use an extended theory of planned behaviour (TPB), which incorporated additional self-efficacy and past behaviour, to predict the intention to engage in moderate-to-vigorous physical activity (MVPA) and the MVPA level of Chinese adolescents. Questionnaires that focused on MVPA, attitude, subjective norm, perceived behavioural control (PBC), self-efficacy and past behaviour related to the MVPA engagement were administered to a sample of 488 young people. Multiple regression analyses provided moderate support for TPB. Three TPB constructs predicted 28.7% of the variance in intentions to engage in MVPA, and that PBC, but not intention, explained 3.4% of the variance in MVPA. Self-efficacy significantly affected intention and behaviour over and above the influence of TPB. Past behaviour had a small but significant improvement in the prediction of intention, but no improvement in the prediction of MVPA. Based on the results, interventions should target adolescent self-efficacy and PBC in physical activity participation. PMID- 26148129 TI - Association between adult atopic dermatitis, cardiovascular disease, and increased heart attacks in three population-based studies. AB - BACKGROUND: Adults with eczema are more likely to smoke cigarettes, consume alcohol, and have sedentary lifestyle. We sought to determine whether adult eczema is associated with increased cardiovascular and cerebrovascular disease. METHODS: Data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES) (n = 4970) and 2010 (n = 27 157) and 2012 (n = 34 525) National Health Interview Survey (NHIS). History of coronary artery disease (CAD), angina, heart attack, stroke, and peripheral vascular disease (PVD) were determined. RESULTS: In NHANES, flexural eczema in the past year was associated with significantly higher odds of CAD (P <= 0.04), heart attack (P <= 0.01), and congestive heart failure (P <= 0.02), but not with stroke (P >= 0.37), in survey-weighted multivariate logistic regression models that controlled for socio-demographics, comorbid asthma, and hay fever. Similarly, in NHIS 2010 and 2012, 1-year history of eczema was associated with significantly higher odds of CAD (P <= 0.02), angina (P <= 0.02), heart attack (P <= 0.047), other heart disease (P < 0.0001), stroke (P <= 0.02), and PVD (<0.0001) in multivariate models. CONCLUSIONS: Adults with atopic dermatitis may have increased cardiovascular disease, heart attack, and stroke. PMID- 26148130 TI - Space Use and Habitat Selection by Resident and Transient Coyotes (Canis latrans). AB - Little information exists on coyote (Canis latrans) space use and habitat selection in the southeastern United States and most studies conducted in the Southeast have been carried out within small study areas (e.g., <=1,000 km2). Therefore, studying the placement, size, and habitat composition of coyote home ranges over broad geographic areas could provide relevant insights regarding how coyote populations adjust to regionally varying ecological conditions. Despite an increasing number of studies of coyote ecology, few studies have assessed the role of transiency as a life-history strategy among coyotes. During 2009-2011, we used GPS radio-telemetry to study coyote space use and habitat selection on the Albemarle Peninsula of northeastern North Carolina. We quantified space use and 2nd- and 3rd-order habitat selection for resident and transient coyotes to describe space use patterns in a predominantly agricultural landscape. The upper limit of coyote home-range size was approximately 47 km2 and coyotes exhibiting shifting patterns of space use of areas >65 km2 were transients. Transients exhibited localized space use patterns for short durations prior to establishing home ranges, which we defined as "biding" areas. Resident and transient coyotes demonstrated similar habitat selection, notably selection of agricultural over forested habitats. However, transients exhibited stronger selection for roads than resident coyotes. Although transient coyotes are less likely to contribute reproductively to their population, transiency may be an important life history trait that facilitates metapopulation dynamics through dispersal and the eventual replacement of breeding residents lost to mortality. PMID- 26148131 TI - Risk factors for postoperative recurrence of intraductal papillary mucinous neoplasms of the pancreas based on a long-term follow-up study: proposals for follow-up strategies. AB - BACKGROUND: The aim of this study was to examine the associations between postoperative clinicopathological features of intraductal papillary mucinous neoplasm (IPMN) and recurrence over a long follow-up period. METHODS: We retrospectively assessed 153 IPMN patients who underwent resection. RESULTS: The resected tumors showed low/intermediate-grade dysplasia (LGD/IGD), high-grade dysplasia (HGD), T1a (stromal invasion <=5 mm), and invasive intraductal papillary mucinous carcinoma (IPMC), in 54.9%, 22.2%, 4.6%, and 18.3% of patients, respectively. The median follow-up period after surgery was 46.4 (6.0 216.3) months, with an overall recurrence rate of 17.0%; the recurrence rates by histological type were 6.0%, 5.9%, 42.9%, and 57.1% for LGD/IGD, HGD, T1a, and invasive IPMC, respectively. Multivariate analysis revealed that recurrences related with tumor location, mural nodule size, presence of invasive cancer, lymph node metastasis, IPMN in the remnant pancreas, and main pancreatic duct dilatation after surgery. Recurrence occurred within the remnant pancreas in all LGD-T1a patients and as extrapancreatic metastasis in all patients with invasive IPMC. Of the total recurrences, 15.4% occurred over 5 years postoperatively. CONCLUSIONS: The postoperative follow-up protocol for patients with LGD-T1a should be similar to non-resected IPMN, and that for invasive IPMC should be the same as for pancreatic ductal adenocarcinoma patients. PMID- 26148132 TI - Efficacy of phenytoin, valproic acid, carbamazepine and new antiepileptic drugs on control of late-onset post-stroke epilepsy in Taiwan. AB - BACKGROUND AND PURPOSE: To assess the efficacy of various antiepileptic drugs (AEDs) for controlling post-stroke epilepsy. METHODS: This nationwide cohort study was conducted by using data from 2004 to 2008 on new occurrence of post stroke epilepsy obtained from the National Health Insurance Research Database of Taiwan. The examined AEDs were phenytoin (PHT), valproic acid (VPA), carbamazepine (CBZ) and new AEDs. Recurrent seizures requiring either emergency room (ER) visits or hospitalization were used to measure the efficacy of seizure control. The Kaplan-Meier failure curve and Cox proportional hazard regression analyses were used to compare the risk of seizure recurrence in patients taking various AEDs. RESULTS: In all, 3622 late-onset post-stroke epilepsy patients were selected. Overall, 1.05 and 0.70 recurrent seizure incidences occurred per 100 person-months based on ER visits [95% confidence interval (CI) 0.95-1.15] and hospitalizations (95% CI 0.62-0.78), respectively. The incidences of ER visits for patients using different AEDs were 1.26, 0.70, 0.43 and 0.38 per 100 person months for PHT, VPA, CBZ and new AEDs, respectively. Compared with patients using PHT, the adjusted hazard ratios for ER visits were 0.56 (95% CI 0.42-0.74; P < 0.001), 0.37 (95% CI 0.18-0.75; P = 0.006) and 0.28 (95% CI 0.15-0.52; P < 0.001) for patients using VPA, CBZ and new AEDs, respectively. The adjusted hazard ratios of hospitalizations for seizure recurrence yielded similar results. CONCLUSIONS: This large nationwide, population-based study demonstrated that late onset post-stroke epilepsy patients using VPA and new AEDs have better seizure control than those using PHT as demonstrated by lower risks of ER visits and hospitalization. PMID- 26148133 TI - Can creatine supplementation form carcinogenic heterocyclic amines in humans? AB - There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2 e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5 f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens. PMID- 26148134 TI - Very short paroxysms account for more than half of the cases of atrial fibrillation detected after stroke and TIA: a systematic review and meta analysis. AB - BACKGROUND: Guidelines suggest that only poststroke atrial fibrillation episodes lasting 30 s or longer should be considered for anticoagulation. However, little evidence supports this recommendation. AIMS: We performed a systematic review and meta-analysis to investigate the frequency of poststroke atrial fibrillation lasting less than 30 s in stroke and transient ischemic attack patients. METHODS: We searched PubMed, Embase, and Scopus from 1980 to June 30, 2014 for studies reporting the detection of poststroke atrial fibrillation of less than 30 s and of 30 s or longer. The primary endpoint was the proportion of screened patients diagnosed with poststroke atrial fibrillation lasting less than 30 s. The secondary endpoint was the proportion of patients diagnosed with poststroke atrial fibrillation shorter than 30 s among the overall number of patients in whom a poststroke atrial fibrillation was detected after stroke or transient ischemic attack. RESULTS: From 28 290 titles, we included nine studies in the random-effects meta-analysis. Among stroke and transient ischemic attack patients without a history of atrial fibrillation, 9.0% (95% confidence interval: 4.9 14.3) experienced episodes of poststroke atrial fibrillation shorter than 30 s. An additional 6.5% (95% confidence interval: 3.2-10.9) experienced episodes of poststroke atrial fibrillation longer than 30 s. Among all patients with poststroke atrial fibrillation, 56.3% (95% confidence interval: 37.7-74.0) had poststroke atrial fibrillation episodes shorter than 30 s during diagnostic evaluation. CONCLUSIONS: The clinical and prognostic significance of poststroke atrial fibrillation episodes shorter than 30 s is unknown. The high frequency of poststroke atrial fibrillation episodes shorter than 30 s justify further investigation into the risk of stroke recurrence and the risk-benefit profile of anticoagulation for this patient population. PMID- 26148136 TI - In Memoriam: Richard G.H. Cotton (1940-2015). PMID- 26148135 TI - Distinct patterns of brain activity in progressive supranuclear palsy and Parkinson's disease. AB - The basal ganglia-thalamo-cortical and cerebello-thalamo-cortical circuits are important for motor control. Whether their functioning is affected in a similar or different way by progressive supranuclear palsy (PSP) and Parkinson's disease (PD) is not clear. A functional magnetic resonance imaging (fMRI) force production paradigm and voxel-based morphometry were used to assess differences in brain activity and macrostructural volumes between PSP, PD, and healthy age matched controls. We found that PSP and PD share reduced functional activity of the basal ganglia and cortical motor areas, but this is more pronounced in PSP than in PD. In PSP the frontal regions are underactive, whereas the posterior parietal and occipital regions are overactive as compared with controls and PD. Furthermore, lobules I through IV, V, and VI of the cerebellum are hypoactive in PSP and PD, whereas Crus I and lobule IX are hyperactive in PSP only. Reductions in gray and white matter volume are specific to PSP. Finally, the functional status of the caudate as well as the volume of the superior frontal gyrus predict clinical gait and posture measures in PSP. PSP and PD share hypoactivity of the basal ganglia, motor cortex, and anterior cerebellum. These patients also display a unique pattern, such that anterior regions of the cortex are hypoactive and posterior regions of the cortex and cerebellum are hyperactive. Together, these findings suggest that specific structures within the basal ganglia, cortex, and cerebellum are affected differently in PSP relative to PD. PMID- 26148137 TI - Use of Attenuated Total Reflectance Mid-Infrared Spectroscopy for Rapid Prediction of Amino Acids in Chinese Rice Wine. AB - The high content of amino acids of Chinese rice wine (CRW), especially essential amino acids makes it a food increasingly demanded by consumers. Rapid detection technique of amino acid content, which is an important quality and function index of CRW, is highly desirable for consumers, producers as well as administrative authorities. In this study, the potential of Fourier transform infrared spectroscopy (FT-IR) as a novel and rapid analytical technique to determine 17 free amino acids in CRW were investigated. Genetic algorithms (GA) and synergy interval partial least squares (SiPLS) were used to select the most efficient spectral variables to improve the prediction precision of the classic partial least squares (PLS) model constructed on the full-spectrum. The results demonstrated that compared with the PLS model using all wavelengths of FT-IR spectra, the prediction precision of model based on the spectral variables selected by GA and SiPLS was significantly improved, especially for arginine and proline. After systemic comparison and discussion, it was found that GA-SiPLS model achieved the best performance, with the correlation coefficient in calibration (R(2) (cal)) higher than 0.80 and the residual predictive deviation higher than 2.00 for all of the free amino acids analyzed in this study. The overall results confirmed that FT-IR combined with efficient variable selection algorithms is a method that may be useful to replace the traditional methods for routine analysis of free amino acids in CRW. PMID- 26148138 TI - Using a novel laminar flow unit provided effective total body hypothermia for neonatal hypoxic encephalopathy. AB - AIM: This was a clinical observational trial on a laminar flow device that provides total body hypothermia for infants with hypoxic ischaemic encephalopathy (HIE). METHODS: We enrolled infants born at up to 35 weeks of gestation, who presented with HIE within six hours of birth. Total body cooling was achieved using the neonatal laminar flow unit for 72 hours, with continuous rectal temperature servo control, isolation and humidification. Outcome measures were cerebral palsy, a Bayley II Mental Development Index score <70, hearing loss or blindness. We compared findings with previously published studies. RESULTS: We included 26 newborn infants (69% male) with a birthweight of 3.341 +/- 1658 g and gestational age of 38.2 +/- 3.2 weeks. The majority (62.6%) had a Sarnat HIE score of three and 38.4% had a score of two. Total body cooling (33-34 degrees C) was achieved in 70 minutes and maintained with servo control, showing very little variability until rewarming. At 18-24 months of age, two of the 18 survivors were diagnosed with cerebral palsy and one was diagnosed with impaired hearing. CONCLUSION: The laminar flow unit proved effective in maintaining moderate total body hypothermia under well-controlled conditions, and our results were very similar to other studies. PMID- 26148139 TI - Immobilization of Carbon Dots in Molecularly Imprinted Microgels for Optical Sensing of Glucose at Physiological pH. AB - Nanosized carbon dots (CDs) are emerging as superior fluorophores for biosensing and a bioimaging agent with excellent photostability, chemical inertness, and marginal cytotoxicity. This paper reports a facile one-pot strategy to immobilize the biocompatible and fluorescent CDs (~6 nm) into the glucose-imprinted poly(N isopropylacrylamide-acrylamide-vinylphenylboronic acid) [poly(NIPAM-AAm-VPBA)] copolymer microgels for continuous optical glucose detection. The CDs designed with surface hydroxyl/carboxyl groups can form complexes with the AAm comonomers via hydrogen bonds and, thus, can be easily immobilized into the gel network during the polymerization reaction. The resultant glucose-imprinted hybrid microgels can reversibly swell and shrink in response to the variation of surrounding glucose concentration and correspondingly quench and recover the fluorescence signals of the embedded CDs, converting biochemical signals to optical signals. The highly imprinted hybrid microgels demonstrate much higher sensitivity and selectivity for glucose detection than the nonimprinted hybrid microgels over a clinically relevant range of 0-30 mM at physiological pH and benefited from the synergistic effects of the glucose molecular contour and the geometrical constraint of the binding sites dictated by the glucose imprinting process. The highly stable immobilization of CDs in the gel networks provides the hybrid microgels with excellent optical signal reproducibility after five repeated cycles of addition and dialysis removal of glucose in the bathing medium. In addition, the hybrid microgels show no effect on the cell viability in the tested concentration range of 25-100 MUg/mL. The glucose-imprinted poly(NIPAM AAm-VPBA)-CDs hybrid microgels demonstrate a great promise for a new glucose sensor that can continuously monitor glucose level change. PMID- 26148141 TI - Controlling the Microstructure of Reverse Micelles and Their Templating Effect on Shaping Nanostructures. AB - Reverse micelles as nanoreactors have been most successful in designing nanostructures of different sizes and shapes. Nevertheless, important questions regarding the explicit roles of intrinsic parameters in modifying soft colloid templates which eventually give rise to variety of nanostructures are still unresolved. In this paper, we have focused on this challenging aspect of microemulsion based synthesis of nanostructures, i.e., how the tunable parameters like water to surfactant molar ratio, solvent properties, and surfactant structure modify the microstructure (size/shape) of reverse micelles (surfactant/cosurfactant/oil/water). Further, we have elucidated the correlation between these nanoreactors with the size and morphology of the evolving nanostructures within the aqueous core (using in situ studies) as well as the finally obtained nanostructures. We have employed fluorescence correlation spectroscopy (FCS), small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and transmission electron microscopy (TEM) to obtain details on the microstructural transformation of reverse micelles and their templating behavior on designing nanostructures, at (near) single droplet level and in an ensemble. The structure (size/shape) of nanoreactors, i.e., reverse micelles, finally guides the size and shape of nanostructures. As the water content increases, it induces the micellar growth and subsequently the growth of nanostructures develops linearly up to a critical value beyond which the finite bending modulus of surfactant film triggers the structural rearrangement of microemulsion droplets (MEDs) and the linear plot shows deviation. Bulkiness of the solvent molecules modulates the ME droplets, and MEDs encapsulates nanostructures by influencing the curvature and rigidity of the surfactant film and results in smaller dimensions of the micellar core, which leads to nanostructures with large aspect ratio. The origin of this structural evolution may be explained in terms of solvent molecular structure, which affects the penetrability of solvent molecules into the surfactant tail region. Interestingly, MEDs with cationic surfactants feature the onset of one-dimensional micellar growth and the shape evolves into a nearly prolate spheriod. Consequently, the growth of the micellar core and dynamical exchange in an anisotropic manner leads to the formation of nanorods. The implication of such studies could be far reaching due to the geometry-dependent novel properties and potential applications of anisotropic nanostructures. PMID- 26148140 TI - Comparison of Traditional and Novel Self-Report Measures to an Alcohol Biomarker for Quantifying Alcohol Consumption Among HIV-Infected Adults in Sub-Saharan Africa. AB - BACKGROUND: In Sub-Saharan Africa (SSA), HIV-infected patients may underreport alcohol consumption. We compared self-reports of drinking to phosphatidylethanol (PEth), an alcohol biomarker. In particular, we assessed beverage-type-adjusted fractional graduated frequency (FGF) and quantity frequency (QF) measures of grams of alcohol, novel nonvolume measures, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). METHODS: We analyzed cohort entry data from the Biomarker Research of Ethanol Among Those with HIV cohort study (2011 to 2013). Participants were HIV-infected past-year drinkers, newly enrolled into care. Self-report measures included FGF and QF grams of alcohol, the AUDIT-C, number of drinking days, and novel adaptations of FGF and QF methods to expenditures on alcohol, time spent drinking, and symptoms of intoxication. PEth levels were measured from dried blood spots. We calculated Spearman's rank correlation coefficients of self-reports with PEth and bias-corrected bootstrap 95% confidence intervals (CIs) for pairwise differences between coefficients. RESULTS: A total of 209 subjects (57% men) were included. Median age was 30; interquartile range (IQR) 25 to 38. FGF grams of alcohol over the past 90 days (median 592, IQR 43 to 2,137) were higher than QF grams (375, IQR 33 to 1,776), p < 0.001. However, both measures were moderately correlated with PEth: rho = 0.58, 95% CI 0.47 to 0.66 for FGF grams and 0.54, 95% CI 0.43 to 0.63 for QF grams (95% CI for difference -0.017 to 0.099, not statistically significant). AUDIT-C, time drinking, and a scale of symptoms of intoxication were similarly correlated with PEth (rho = 0.35 to 0.57). CONCLUSIONS: HIV-infected drinkers in SSA likely underreport both any alcohol consumption and amounts consumed, suggesting the need to use more objective measures like biomarkers when measuring drinking in this population. Although the FGF method may more accurately estimate drinking than QF methods, the AUDIT-C and other nonvolume measures may provide simpler alternatives. PMID- 26148142 TI - Amyloid beta Peptides and Cognitive Functions in Patients with Pseudoexfoliation Syndrome. AB - PURPOSE: The aim of this study was to evaluate if there is any relation between the Alzheimer's peptides (amyloid beta-40 and beta-42) concentration in plasma and aqueous humor as well as cognitive functions with pseudoexfoliation syndrome (PEX). METHODS: One-hundred forty-two patients with PEX have been included for this study; median age: 75 years (Q1 = 71,5; Q3 = 80,0). Control group comprised 93 subjects aged 74 years (Q1 = 68,0; Q3 = 80,0). Amyloid beta-40 and beta-42 (Abeta-40, Abeta-42) concentrations were assessed in plasma in 73 PEX patients and 49 controls. Abeta-40 concentration in aqueous humor was measured in 31 patients from each group. Mini Mental State Examination (MMSE) and Clock Drawing Tests were performed in 83 PEX patients and 36 controls. RESULTS: The differences between amyloid concentrations both in plasma and in aqueous humor in PEX and control groups were not statistically significant. There were no differences in MMSE and Clock Drawing Tests between groups. CONCLUSION: Our results do not indicate any relation between PEX and Alzheimer's amyloids or cognitive functions in cataract patients. PMID- 26148143 TI - Increased technetium-99 m hydroxy diphosphonate soft tissue uptake on bone scintigraphy in chronic kidney disease patients with secondary hyperparathyroidism: correlation with hyperphosphataemia. AB - In bone scan patients with dialysis-treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium-99 m hydroxy/methylene diphosphonate (Tc-99 m-HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and/or hyperphosphataemia. As human vascular smooth muscle cells produce hydroxyapatite during cell culture with increased phosphate levels and as Tc-99 m-HDP/MDP primarily binds to hydroxyapatite, we hypothesized that soft tissue accumulation would be found in patients with hyperphosphataemia. We identified 63 CKD patients diagnosed with secondary hyperparathyroidism admitted for Tc-99 m-HDP bone scan. Baseline characteristics and mean concentrations of biochemical markers (including P calcium and P-phosphate) taken 0-3 months prior to the bone scans were collected. Soft tissue uptake was detected on bone scans in 37 of 63 (59%) patients. Primary locations were in the heart (27/37 = 73%), muscles (12/37 = 32%), lung (9/37 = 24%) and gastrointestinal tract (6/37 = 16%), and 13 of 37 (35%) patients had simultaneous uptake in more than one location. Regarding biochemical markers, patients with soft tissue uptake only differed from patients without in terms of plasma phosphate levels (1.95 +/- 0.15 (n = 37) versus 1.27 +/- 0.08 (n = 26), P = 0.0012). All patients with myocardial uptake (n = 27) had a coronary arteriography-verified history of coronary artery disease (CAD), whereas CAD was only present in six of the 36 patients without myocardial uptake. In conclusion, dialysis-treated CKD patients with secondary hyperparathyroidism have a high incidence of soft tissue uptake, and this finding is strongly correlated with elevated phosphate, but not calcium values. PMID- 26148144 TI - Effect of topical prostaglandin analogues on corneal hysteresis: author's reply. PMID- 26148145 TI - Reduced oxygen cost of running is related to alignment of the resultant GRF and leg axis vector: A pilot study. AB - This pilot study investigated whether a 10-week running program (10wkRP), which reduced the oxygen cost of running, affected resultant ground reaction force (GRF), leg axis alignment, joint moment characteristics, and gear ratios. Ten novice, female runners completed a 10wkRP. Running kinematics and kinetics, in addition to oxygen consumption ( V O 2 ) during steady-state running, were recorded pre- and post-10wkRP. V O 2 decreased (8%) from pre-10wkRP to post 10wkRP. There was a better alignment of the resultant GRF and leg axis at peak propulsion post-10wkRP compared with pre-10wkRP (10.8 +/- 4.9 vs 1.6 +/- 1.2 degrees ), as the resultant GRF vector was applied 7 +/- 0.6 degrees (P = 0.008) more horizontally. There were shorter external ankle moment arms (24%) and smaller knee extensor moments (23%) at peak braking post-10wkRP. The change in V O 2 was associated with the change in alignment of the resultant GRF and leg axis (rs = 0.88, P = 0.003). As runners became more economical, they exhibited a more aligned resultant GRF vector and leg axis at peak propulsion. This appears to be a self-optimization strategy that may improve performance. Additionally, changes to external ankle moment arms indicated beneficial low gear ratios were achieved at the time of peak braking force. PMID- 26148146 TI - Hypoxia-induced apoptosis and mechanism of epididymal dysfunction in rats with left-side varicocele. AB - To investigate the relationship between hypoxia and epididymal dysfunction and the mechanism of epididymal dysfunction in rats with left-side varicocele, a total of 45 male Wistar rats were randomly divided into three groups in average. The expression of hypoxia-inducible factor-1alpha (HIF-1alpha) was detected by Western blot and immunohistochemical analysis respectively. HIF-1alpha was expressed in the experimental group, and the positive rate was significantly higher than that of either the sham or the control group (P < 0.05). The apoptosis index (AI) of epididymal epithelium was higher in the experimental group (7.25 +/- 2.56) than that in either the sham (0.52 +/- 0.57, P < 0.01) or the control group (0.08 +/- 0.13, P < 0.01). Additionally, the levels of sialic acid and carnitine were lower in the experimental group than that in either the sham or the control group (P < 0.05) and were significantly negatively correlated with HIF-1alpha expression (r = -0.620, P = 0.014, and r = -0.610, P = 0.016 respectively). It is concluded that left-side varicocele could cause epididymal hypoxia and epididymal dysfunction. Moreover, HIF-1alpha maybe act as useful factor to predict germ cell apoptosis in varicocele. PMID- 26148147 TI - Regional distribution of body fat in relation to DNA methylation within the LPL, ADIPOQ and PPARgamma promoters in subcutaneous adipose tissue. AB - Obesity may be related to differential DNA methylation and thus to differential expression of key genes in adipose tissue metabolism, such as LPL, ADIPOQ and PPARgamma. Using subcutaneous adipose tissue (SAT) from 59 individuals of the European Prospective Investigation into Cancer and Nutrition-Potsdam study, we performed quantitative DNA methylation analysis within the promoters of LPL (LPL CG1 and -CG2), ADIPOQ (ADIPOQ-CG1 and-CG2) and PPARgamma (PPARgamma-CG1). We then studied DNA methylation in relation to SAT gene expression, body composition measured using whole-body magnetic resonance imaging, body mass index (BMI), waist circumference (WC) and long-term changes in BMI and WC. For LPL-CG1 and LPL CG2, higher methylation levels were associated with lower LPL expression, but with higher past WC gain. LPL-CG1 was also positively associated with BMI, WC, and visceral and subcutaneous fat mass. ADIPOQ-CG1 or -CG2 methylation exhibited no association with ADIPOQ expression or with anthropometric parameters. PPARgamma-CG1 methylation was significantly higher in individuals with higher visceral fat mass. Among the investigated sites, LPL-CG1 methylation showed the strongest association with gene expression and regional body fat distribution, thereby possibly linking the degree of obesity with major metabolic processes in SAT. PMID- 26148148 TI - Subetta increases phosphorylation of insulin receptor beta-subunit alone and in the presence of insulin. AB - It has been previously shown that Subetta (a drug containing released-active forms of antibodies to the insulin receptor beta-subunit and antibodies to endothelial nitric oxide synthase) stimulated insulin-induced adiponectin production by mature human adipocytes in the absence of insulin. Therefore, it was assumed that Subetta could activate the insulin receptor. To confirm this hypothesis, the capacity of Subetta to activate the insulin receptor in mature human adipocytes in the absence or presence of the insulin was investigated. Cells were incubated either with Subetta or with vehicle, or with basal medium for 3 days. Then, adipocytes were treated with water or insulin (100 nm) for 15 min. Following treatment, lysates were prepared and phosphorylation of insulin receptor beta-subunits was analyzed by western blot analysis. It was shown that Subetta significantly increased (P<0.001) the 'phosphorylated-insulin receptor beta-subunit/total insulin receptor beta-subunit' ratios in both the presence and the absence of insulin. These results support previously published data and indicate that Subetta could activate the insulin receptor through the effect on its beta-subunits, whose conformational state is essential for insulin receptor activation. This action might serve as one of the primary mechanisms of the drug's antidiabetic effect. PMID- 26148150 TI - And, what comes next? PMID- 26148149 TI - Connecting biology and organic chemistry introductory laboratory courses through a collaborative research project. AB - Modern research often requires collaboration of experts in fields, such as math, chemistry, biology, physics, and computer science to develop unique solutions to common problems. Traditional introductory undergraduate laboratory curricula in the sciences often do not emphasize connections possible between the various disciplines. We designed an interdisciplinary, medically relevant, project intended to help students see connections between chemistry and biology. Second term organic chemistry laboratory students designed and synthesized potential polymer inhibitors or inducers of polyglutamine protein aggregation. The use of novel target compounds added the uncertainty of scientific research to the project. Biology laboratory students then tested the novel potential pharmaceuticals in Huntington's disease model assays, using in vitro polyglutamine peptide aggregation and in vivo lethality studies in Drosophila. Students read articles from the primary literature describing the system from both chemical and biological perspectives. Assessment revealed that students emerged from both courses with a deeper understanding of the interdisciplinary nature of biology and chemistry and a heightened interest in basic research. The design of this collaborative project for introductory biology and organic chemistry labs demonstrated how the local interests and expertise at a university can be drawn from to create an effective way to integrate these introductory courses. Rather than simply presenting a series of experiments to be replicated, we hope that our efforts will inspire other scientists to think about how some aspect of authentic work can be brought into their own courses, and we also welcome additional collaborations to extend the scope of the scientific exploration. PMID- 26148151 TI - The meaning of teaching and learning for professors. AB - OBJECTIVE: This work sought to comprehend the meaning professors from the Faculty of Nursing at Universidad de Antioquia (Colombia) assign to teaching and learning processes. METHODOLOGY: This was an educational qualitative, evaluative investigation, with ethnographic focus, conducted from 2011 to 2013. The information collection techniques were: semi-structured interview, discussion groups, y el documentary analysis. A total of 70 professors from the undergraduate Nursing program at Universidad de Antioquia participated in the study. RESULTS: Teaching for professors means complexity, transmission of information and knowledge, cooperation with students, interaction, and transformation of reality. This does not merely depend on the vocation or on the will to carry it out; on the contrary, professors must have professional, disciplinary, and pedagogical formation. Learning for the professors means that students understood, comprehended, and were able to put the theory into practice. Also, students must commit to their own learning. CONCLUSION: The conceptions professors have of teaching and learning processes guide the meaning they assign to said processes and stem from their own experience, culture, professional and disciplinary formation. Assigning new meaning to teaching in nursing opens the possibility of reorienting the teaching practice. PMID- 26148152 TI - Humanized care: A relationship of familiarity and affectivity. AB - OBJECTIVE: This work sought to understand the meaning of humanized nursing care in the experience of participants, nurses, patients, and their relatives. METHODOLOGY: This was an interpretive phenomenological study based on in-depth interviews, which included 16 adult participants and was conducted in Medellin, Colombia, between December 2012 and March 2013. RESULTS: The patient?s situation, the nurses? communication skills, and the condition of both, as human beings, influence upon the words, gestures and attitudes during the nurse-patient relationship, where the presence, that which is done, and how it is done permit leaving an important impression on patients and their relatives. CONCLUSION: The interaction between patients and nurses goes through various stages until achieving the necessary empathy, compassion, affection, and familiarity to account for humanized care. PMID- 26148153 TI - Occupational stress among nursing technicians and assistants: coping focused on the problem. AB - OBJECTIVE: To analyze the association between strategies used to cope with occupational stress that are focused on the problem wand the personal characteristics of nursing technicians and assistants. METHODOLOGY: This quantitative and correlational study was conducted in a large teaching hospital in the Sao Paulo State, Brazil, in 2013. A randomized sample with 310 participants (198 nursing assistants and 112 nursing technicians) comprised the study population. Data were collected using a sociodemographic characteristics questionnaire and Scale of Ways of Coping with Problems. Data were submitted to univariate analysis, and variables with statistical significance (p<0.20) were submitted posteriorly in a multiple regression model. RESULTS: Most employees were women (76.1%) older than 40 years (67.7%), had nine to 11 years of formal education (73.5%), had a partner (58.7%), were Catholic (53.2%), and had children (74.5%). The final multiple regression model consisted of variable years of formal education and number of children. CONCLUSION: In this study, formal education and number of children were more strongly associated with a greater use of coping strategies focused on the problem. Such a strategy is related to minimal vulnerability to stress related to the working environment. PMID- 26148154 TI - Risk Factors for new accidental falls in elderly patients at traumatology ambulatory center. AB - OBJECTIVE: To identify the risks factors for new accidental falls in elderly patients attended in the Traumatology Ambulatory of a University hospital in Rio Grande do Sul, Brazil. METHODOLOGY: Quantitative study of the type of multiple cases. Performed at the traumatology ambulatory, amongst fifteen elders that attended the inclusion criteria: age of sixty or more; patient at the traumatology ambulatory because of a fall motivated by accident, oriented and in conditions of answer an interview of data collectors. The data collection was made between April and June, 2013, with the Elderly Nursing Core Set scale (Lopes & Fonseca). The data analysis was made by a descriptive structure, which helped identify the existence of relation patterns among the cases. RESULTS: The risk factors for new accidental falls identified with larger incidence amongst the elders studied were: impaired balance (15/15), age above 65 (11/15), use of antihypertensive drugs (9/15), absence of non-slip material at home environment (7/15), in seven cases; rugs scattered at the floor of the house (6/15). CONCLUSION: The combination of intrinsic and extrinsic factors that include the environmental risks is considered a much more relevant cause to occur the new falls. The minimization of the home dangers, allied to the control of the elder intrinsic factors, may reduce the risks of causes. In that sense, is necessary that the nursing team make available more attention to the elderly assisted at the ambulatories, mainly those with sequelae due to fall accidents. PMID- 26148155 TI - The health team and the safety of the mother-baby binomial during labor and birth. AB - OBJECTIVE: Describe the performance of the health care team regarding the safety of both mother and baby during labor and birth. METHODOLOGY: Qualitative, descriptive, exploratory study. The subjects were: obstetricians, residents in Obstetrics, pediatricians, nurses, and nursing technicians. The observation technique was used for data collection in a public hospital, between March and July 2010. The data was subjected to thematic content analysis. CEP-GHC (No. 10/001). RESULTS: Data analysis revealed the themes: empathic support, woman's companion, skin-to-skin contact (SSC), and birth environment. The team promoted safe care through empathic support for women and appreciation and respect for the escort. In relation to SSC and the enabling environment for the reception of the newborn, efforts are still needed for these practices to be configured in secure care circumstances. CONCLUSION: The Nurse played a differential role in the team for the realization of safe care, because she was predominant in supporting women and promoting CPP. PMID- 26148156 TI - Comparative study of quality of life of elderly living in condominiums versus community dwellers. AB - OBJECTIVE: To compare the quality of life of elderly living at a geriatric institution with that of elderly living in the community. METHODOLOGY: Quantitative study in which the quality of life of 50 elderly living in condominiums was compared with that of 173 community dwellers. To assess the quality of life, the instruments WHOQOL-BREF and WHOQOL-OLD were applied. The data were collected between November 2011 and February 2012. RESULTS: The groups differed significantly with regard to the domains: physical, environment, functioning of the senses and participation, which were better in the condominium residents; while the community dwellers scored higher in the domain intimacy. CONCLUSION: Different factors can interfere in the elderly's quality of life, including the place of residence, which indicates the need for further monitoring by health professionals, especially nurses, with a view to outlining strategies to maintain the elderly's quality of life. PMID- 26148157 TI - Impact of curricular change on the perception of the educational environment by nursing students. AB - OBJECTIVE: This study sought to evaluate the impact of curricular change on the perception of the Educational Environment (EE) in nursing students. METHODOLOGY: This was a cross-sectional study. Two consecutive cohorts were evaluated during the second year, entering 2010 (N: 58) and 2011 (N: 57) for former and new curriculum, respectively. A sociodemographic survey and perception of the EE was applied through the Dundee Ready Educational Environment Measure (DREEM) questionnaire. RESULTS: No differences were detected in the sociodemographic variables between the cohorts. Both groups evaluated EE more positively than negatively. The total average score of the perception of the EE by the 2010 cohort was of 132 points and by the 2011 cohort of 126 points, a statistically significant difference. Upon analyzing the survey items, it was observed that poorer perception exists of the learning atmosphere and of the social environment, as well as poorer assessment of the academic skills in the 2011 cohort compared to the 2010 cohort. The good preparation the students are receiving for the profession and the relevance of the assignments they are learning are considered strengths by the students from both groups. CONCLUSIONS: In spite of how positive the curricular changes could seem, perception of the EE in both cohorts does not reach the excellent category. Before any changes are made to the curriculum, it is indispensable to take into account how the academic load might affect the students. PMID- 26148158 TI - Spirituality and humanization according to nursing undergraduates: an action research. AB - OBJECTIVE: To know the conceptions of undergraduates from the Teaching Diploma Program with Bachelor degree in Nursing at a public state-owned higher education institution in an interior city in the State of Sao Paulo about spirituality and humanization, as well as to propose educative action in that sense. Methodoly. A qualitative study was undertaken, using the action research method. The data were collected in the second semester of 2012 through participant observation, registered in a field diary, and interviews with the help of questionnaires. For the interpretative data analysis, categorization was used. RESULTS: The implicit predominance of the technical-procedure care discourse was observed, to the detriment of the educational care discourse, as complementary constructs, according to the participant' statements. Nevertheless, the educational action permitted constructivism and the problematization of knowledge. CONCLUSION: Although the results may not reflect the reality at the investigated institution, it is concluded that the academic education of nurse educators is a moment of possibilities to include spirituality and humanization, regarding the development of competences that grant individual support to patients and families, in health promotion and coping with disease situations. PMID- 26148159 TI - The knowledge of expert nurses and the practical-reflective rationality. AB - OBJECTIVE: To identify the characteristics of an expert nurse. METHODOLOGY: A group of 49 nurses starting their Master's degree was asked to answer the following question: ''Which characteristics and skills distinguish a novice from an expert nurse?'' The answers were analyzed and classified based on Bardin's content analysis. RESULTS: Through a three-stage classification process, the competences and skills assigned to expert nurses were divided into 17 categories. These nurses showed wide-ranging skills and acquired meta-competencies. Expert nurses are characterized by their leadership, supervision and ability to manage change, as well as their communication and relational skills. They have the ability to act reflectively, plan, systematize and consistently assess; they also show more dexterity. They have more adaptive skills, confidence and achieve a broader view. They are competent while managing conflicts and stress, as well as articulating theory and practice; they create knowledge, make use of research, respond to complex situations and are capable of making decisions. CONCLUSION: Expert nurses have anticipation skills, insight, use detailed observation, take immediate action and are able to define priorities; they keep context in mind and have a tendency for specialization. PMID- 26148160 TI - Emotional state of primigravid women with pregnancy susceptible to prolongation. AB - OBJECTIVE: This study sought to know the perception of the emotional state of women with pregnancy susceptible to prolongation. METHODOLOGY: The research was conducted with qualitative descriptive methodology, founded on in-depth individual interviews of 7 gestants susceptible to prolongation, with ages between 21 and 32 years and duration of the pregnancy comprised between 40+5 and 41+4 weeks. RESULTS: The emotional state varies throughout the pregnancy; once the probable date of delivery has passed, the emotional well-being is altered by fear of pain during delivery, possible complications, and caring for the newborn, presenting a state of nervousness due to the imminent delivery. In addition, the women described the need for the presence of a companion during and after the delivery. CONCLUSION: Fear can affect negatively the subjective experience of the pregnancy during its final phase, the delivery process, and the transition to maternity in gestants with pregnancy susceptible to prolongation. These women need support and specific education from the midwife according to their individual needs. PMID- 26148161 TI - Aspects that facilitate or interfere in the communication process between nursing professionals and patients in critical state. AB - OBJECTIVE: To describe aspects facilitating or interfering in the communication process between nursing professionals and patients in critical state. METHODOLOGY: Descriptive study conducted during the second semester of 2013, with the participation of 112 nurses who work in Intensive Care Units of Bogota (Colombia). To gather the information, the researchers designed a survey. RESULTS: A total of 91.6% of the nursing professionals considers communication important with patients and their families; 75.9% seeks to provide, during the care interventions, physical care and communicate per shift from two to four times with the patient and from one to two times with the family; 50% states feeling afraid to communicate; only 53.7% integrate their emotions in the patient's physical care. Regarding the elements of communication developed during their graduate formation, 42.8% received tools of therapeutic communication during their undergraduate studies and only 33.0% during graduate studies. It is worth to indicate that 80.36% of the Intensive Care Units, where the nursing professionals work, privilege interventions aimed at satisfying physiological needs. CONCLUSION: The communication process between nurses and patients in critical state is limited by restrictive institutional policies and by the nurse' scarce academic formation. The need exists to start a process of change in relation to models of professional practice deeply rooted in physical care of critical patients to establish models that, during physical care, are centered on communication and the patient-family-professional relationship. PMID- 26148162 TI - Profile of nursing diagnoses in patients with respiratory disorders. AB - OBJECTIVE: Identify the profile of nursing diagnoses in patients with respiratory disorders. METHODOLOGY: A descriptive and cross-sectional study involving 38 patients with respiratory problems, of referral hospitals, in a city in northeastern Brazil, in the period from August to October, 2012. Data collection was performed using a form and diagnostic inference was made according with the Taxonomy II of NANDA I. RESULTS: The average age of the patients was 46 years and males predominated (60.5%). The most frequent nursing diagnoses were: Risk for infection (97.3%), Acute pain (68.4%), Poor knowledge (68.4%), Sedentary lifestyle (65.7%), Ineffective airway clearance (65.7%), Risk-prone health behavior (63.1%), Activity intolerance (52.6%) and Disturbed sleep pattern (33.3%). Evaluated patients exhibited an average of 8.6 nursing diagnoses (SD = 2.8). With respect to the defining characteristics and related factors the average per person was 7.2 and 9.3, respectively. CONCLUSION: In this group of patients the most frequent diagnoses were the domain activity/rest. Knowledge of nursing diagnoses profile presented by people with respiratory disorders is important, because it is part of the Nursing Process and nurses who take care of such patients should exercise them in their care practice. Knowledge of the mains nursing diagnosis presented by patients with respiratory disorders are important for the practice of nurses who care for these patients, because it allows the choice of responses to problems of their clientele. PMID- 26148163 TI - Nursing diagnoses and adaptation problems among chronic renal patients. AB - OBJECTIVE: To identify similarities between NANDA International nursing diagnoses and Roy's adaptation model among chronic renal patients undergoing hemodialysis. METHODOLOGY: Cross-sectional and descriptive study with 178 individuals selected, through consecutive convenience sampling, in a dialysis center located in the Northeast of Brazil. The study was conducted between October 2011 and February 2012. Data collection instruments included an interview form and a physical assessment. RESULTS: Similarity was found between 20 nursing diagnoses and 22 adaptation problems. Roy's adaptation modes that presented these relationships were: physiological, self-conception and role function. CONCLUSION: There are similarities between the two typologies. Furthermore, the use of the nursing process from the perspective of a theory inherent to the field supports care delivery and strengthens scientific knowledge in the profession. PMID- 26148164 TI - Material world and social recognition: Nursing care in Spain (1855-1955). AB - OBJECTIVE: This study sought to recognize the active and symbolic role played by the objects from the material world for nursing care in Spain between 1855 and 1955. METHODOLOGY: This was a historical study using procedures from founded theory. The information sources were eight handbooks for the formation of healthcare professionals published in Spain, during the period of interest. The information was gathered from March 2012 to June 2013. During this period, the sources were revised comprehensively and bibliographic information, description of instruments, and analysis files were made; methodological and analytic memoranda were written. Forty-five procedures and 360 material objects were registered. RESULTS: The categories ''principal and secondary objects'' and ''guarded objects'' reveal the influence exerted by the objects from the material world for care. CONCLUSION: In Spain, between 1855 and 1955, nursing care was carried out within a scenario comprised of objects with secondary status and situated within the periphery of care, as well as by guarded objects that professionals could not use. This material world influenced the social recognition of healthcare professionals at the time and the visibility of their work. PMID- 26148165 TI - Adaptation to chronic benign pain in elderly adults. AB - OBJECTIVE: This study sought to comprehend and analyze the experience of living with chronic benign pain during aging from the perspective of the adaptation model by Callista Roy. METHODOLOGY: Ours was an exploratory descriptive study using for analysis tools from the theory based on criteria by Strauss and Corbin. The strategy involved in-depth interviews of 10 elderly adults residing in Medellin, Antioquia, and Chia, Cundinamarca (Colombia) with chronic benign pain. RESULTS: In elderly adults, behaviors were identified that were secondary to the presence of pain and which are consequence of the capacity to adapt to their experience, managing to modify the environment by using internal and external resources that permitted their controlling the pain-generating stimuli in the human beings adaptation means based on the Adaptation model by Callista Roy. CONCLUSION: Elderly adults respond effectively to their new secondary condition: presence of benign pain in all the means of adaptation. PMID- 26148166 TI - Bachelor of nursing student' attitude towards people with mental illness and career choices in psychiatric nursing. An Indian perspective. AB - OBJECTIVE: To examine undergraduate nursing student' attitudes toward people with mental illness and mental health nursing. METHODOLOGY: This was a cross sectional descriptive study carried out among conveniently selected nursing students (N=116). Data was collected through self- reported questionnaires. RESULTS: Majority of the participants agreed that the theoretical (81.1%) and clinical placement (85.4%) was adequate. Similarly, 62.9% would like to apply for a post basic program in Psychiatric nursing and 69.8% of the students intend to pursue their career as mental health nurses. However, a majority expressed that people with mental illness are unpredictable (80.2%), cannot handle too much responsibility(71.5%), more likely to commit offences or crimes (84.5%) and more likely to be violent (44%). Negative stereotype domain had significant relationships with future career (r=-0.2, p= 0.003), course effectiveness (r= 0.4, p<0.001), valuable contribution (r=-0.3, p<0.001) and readiness of the students (r=-.3, p<.000) domains. CONCLUSION: There is an urgent need to address these negative perceptions among nursing students towards people with mental illness. Innovative teaching strategies and appropriate changes in the nursing curriculum is required to prepare future nurses to deal mental health problems effectively. PMID- 26148167 TI - Clinical indicators to monitor patients with risk for ineffective cerebral tissue perfusion. AB - OBJECTIVE: Select and validate the clinical indicators to monitor patients on risk for ineffective cerebral tissue perfusion, according to the Nursing Outcomes Classification (NOC). METHODOLOGY: Validation study carried out between November 2012 and August 2013, in a Brazilian hospital. Seventeen judges nurses evaluated the clinical indicators of Nursing Outcomes, according to NOC for patients on risk for ineffective cerebral tissue perfusion. In the first stage, were selected the nursing results for the assessment of the studied diagnosis and, in the second nurses assessment the importance of the indicators of the validated results in the previous step through a five points Likert scale (1 = not important to 5 = extremely important). Were used the content validity index (CVI) that corresponds to the calculation of weighted averages of them marks awarded for each indicator, as it considered the following weights: 1=0.00, 2=0.25, 3=0.50; 4=0.75; 5=1.00. For categorization, the CVI considered as critical = >=0.80; supplementary =>=0.50 to 0.79 and were disposed results <0.50. RESULTS: Of the 9 nursing results, only the cerebral tissue perfusion obtained a 100% consensus. The CVI of the 18 indicators of this result showed that five were validated as critical (impaired neurological reflexes, systolic blood pressure, diastolic blood pressure, reduced level of consciousness and mean arterial pressure), 12 were validated as supplementary (Agitation, Impaired cognition, Intracranial pressure, Syncope, Vomiting, Findings of cerebral angiography, Headache, Restlessness, Fever, Unexplained anxiety, listlessness and Hiccughs) and one was disposed (carotid bruit). CONCLUSIONS: The validation of information about the conditions of risk may allow early intervention to minimize the consequences of ineffective cerebral tissue perfusion. PMID- 26148168 TI - Ethical considerations in research. Focus on vulnerable groups. AB - The purpose of this paper was to describe the need to protect the rights of human subjects participating in nursing research, and procedures for doing so. The path taken to the task at hand was to approach the topic by discussing the philosophical underpinnings of human subject protection and describing the approach for doing this in all cases where humans are used as research subjects. These underpinnings include specific ethical principles of respect for persons, beneficence, and justice, and the procedures used in the U.S. for protecting the rights of human subjects. Once the process was clarified, the considerations necessary to protect the special groups referred to as ''vulnerable'' are discussed. Given the author's access to U.S. documents and the fact that U.S. government agencies took early steps to formalize rules and regulations for the protection of human subjects, vulnerable or otherwise, the experience of the United States was selected for presentation. It is recognized that there are now relevant international documents that are exceedingly helpful, and also, that various countries may have their own guidelines for investigators to follow. In such cases researchers can engage in comparative analysis between their own guidance and the processes described here, and decide their path accordingly. PMID- 26148169 TI - The effects of adding upper and lower subcostal transversus abdominis plane blocks to a lateral transversus abdominis plane block after laparoscopic cholecystectomy: A randomised, double-blind clinical trial. PMID- 26148170 TI - Urapidil versus nicardipine in preeclamptic toxaemia: A randomised feasibility study. PMID- 26148171 TI - How to minimise ventilator-induced lung injury in transplanted lungs: The role of protective ventilation and other strategies. AB - Lung transplantation is the treatment of choice for end-stage pulmonary diseases. In order to avoid or reduce pulmonary and systemic complications, mechanical ventilator settings have an important role in each stage of lung transplantation. In this respect, the use of mechanical ventilation with a tidal volume of 6 to 8 ml kg(-1) predicted body weight, positive end-expiratory pressure of 6 to 8 cmH2O and a plateau pressure lower than 30 cmH2O has been suggested for the donor during surgery, and for the recipient both during and after surgery. For the present review, we systematically searched the PubMed database for articles published from 2000 to 2014 using the following keywords: lung transplantation, protective mechanical ventilation, lung donor, extracorporeal membrane oxygenation, recruitment manoeuvres, extracorporeal CO2 removal and noninvasive ventilation. PMID- 26148172 TI - Assessment and Selection of Competing Models for Zero-Inflated Microbiome Data. AB - Typical data in a microbiome study consist of the operational taxonomic unit (OTU) counts that have the characteristic of excess zeros, which are often ignored by investigators. In this paper, we compare the performance of different competing methods to model data with zero inflated features through extensive simulations and application to a microbiome study. These methods include standard parametric and non-parametric models, hurdle models, and zero inflated models. We examine varying degrees of zero inflation, with or without dispersion in the count component, as well as different magnitude and direction of the covariate effect on structural zeros and the count components. We focus on the assessment of type I error, power to detect the overall covariate effect, measures of model fit, and bias and effectiveness of parameter estimations. We also evaluate the abilities of model selection strategies using Akaike information criterion (AIC) or Vuong test to identify the correct model. The simulation studies show that hurdle and zero inflated models have well controlled type I errors, higher power, better goodness of fit measures, and are more accurate and efficient in the parameter estimation. Besides that, the hurdle models have similar goodness of fit and parameter estimation for the count component as their corresponding zero inflated models. However, the estimation and interpretation of the parameters for the zero components differs, and hurdle models are more stable when structural zeros are absent. We then discuss the model selection strategy for zero inflated data and implement it in a gut microbiome study of > 400 independent subjects. PMID- 26148173 TI - Suspicious Findings at Digital Breast Tomosynthesis Occult to Conventional Digital Mammography: Imaging Features and Pathology Findings. AB - To review the imaging and pathologic features of a series of lesions detected at digital breast tomosynthesis (DBT), which are occult to conventional digital mammography (DM). We retrospectively reviewed 268 consecutive breast imaging reporting and data system 4 and 5 lesions imaged with both DM and DBT at our facility from July 2012 through April 2013. For each lesion, we recorded the mammographic finding, breast density, mode of biopsy, and pathology results. A total of 19 lesions were identified at DBT that were occult to DM. Sixty three percent (12/19) of these lesions were identified in dense breasts. Architectural distortion was seen in 74% (14/19) of cases and spiculated masses accounted for the remaining 26% (5/19). The positive predictive value of biopsy was 53% (10/19). Seven cases were infiltrating ductal carcinomas and three were infiltrating lobular carcinomas. High-risk lesions accounted for 47% (9/19) of the lesions, the majority of which were radial scars 67% (6/9). Eighty four percent (16/19) of the lesions underwent ultrasound guided core biopsy while the remainder underwent magnetic resonance imaging guided core biopsy. DBT may demonstrate suspicious lesions that are occult to DM, particularly in women with dense breasts. Such lesions have a high likelihood of malignancy and warrant biopsy. PMID- 26148174 TI - Prognostic impact of acquisition of cytogenetic abnormalities during the course of chronic myelomonocytic leukemia. AB - Karyotypic abnormalities are detected in 20-40% of chronic myelomonocytic leukemia (CMML) patients at initial diagnosis and have been shown to correlate with patients' outcome. The significance of acquisition of cytogenetic abnormalities (ACA) during the course of CMML, however, is largely unknown. In a cohort of 314 CMML patients, karyotypic abnormalities were detected in 106 (34%) patients at the time of diagnosis; and ACA were detected in 80 (25%) patients after a median interval of 17 months (range, 2-117 months). The most frequently observed ACA were a complex karyotype, followed by +21, -7/del(7q), del(20q), i(17q), and -17/del(17p). ACA appeared to occur more frequently in patients with a normal or lower risk karyotype. Progression to AML was seen in 44 of 80 (55%) patients with ACA versus 67 of 234 (29%) patients without ACA (P < 0.0001). Presence of ACA predicted an inferior leukemia-free survival (LFS) by univariate (P = 0.0435) and multivariate analysis (HR = 1.892, P = 0.006). While acquisition of a complex karyotype was positively correlated with AML progression (P = 0.0086), del(20q) was associated with a stable disease (P = 0.0198). We conclude that ACA occur in ~20-30% of CMML patients during the course of disease, and are significantly associated with AML progression and a shorter LFS. Karyotypic abnormalities, either present at diagnosis or acquired during the course of disease, have prognostic implication in CMML patients. PMID- 26148175 TI - Mesenchymal stem cell-based gene therapy: A promising therapeutic strategy. AB - Mesenchymal stem cells (MSCs) are multipotent stromal cells that exist in bone marrow, fat, and so many other tissues, and can differentiate into a variety of cell types including osteoblasts, chondrocytes, and adipocytes, as well as myocytes and neurons. Moreover, they have great capacity for self-renewal while maintaining their multipotency. Their capacity for proliferation and differentiation, in addition to their immunomodulatory activity, makes them very promising candidates for cell-based regenerative medicine. Moreover, MSCs have the ability of mobilization to the site of damage; therefore, they can automatically migrate to the site of injury via their chemokine receptors following intravenous transplantation. In this respect, they can be applied for MSC-based gene therapy. In this new therapeutic method, genes of interest are introduced into MSCs via viral and non-viral-based methods that lead to transgene expression in them. Although stem cell-based gene therapy is a relatively new strategy, it lights a new hope for the treatment of a variety of genetic disorders. In the near future, MSCs can be of use in a vast number of clinical applications, because of their uncomplicated isolation, culture, and genetic manipulation. However, full consideration is still crucial before they are utilized for clinical trials, because the number of studies that signify the advantageous effects of MSC-based gene therapy are still limited. PMID- 26148176 TI - Spectroscopic analysis and the excellent reusability of sphere-capped ferrocene in the oxidation of glucose oxidase. AB - Sphere-capped ferrocene nanospheres with Schiff base spacers have been prepared using a template, and used as carriers to immobilize glucose oxidase (GOx). GOx immobilized on spheres with one C-spacer (APS-Fc) exhibited high binding affinity to the substrate, which was attributed to appropriate position for the GOx conformation. When glucose oxidase was immobilized with spacers of different lengths, it was found that storage stability decreased with increasing the length of the spacer. It has been found that nanospheres, including capped ferrocene, exhibit good performance as the immobilized supporters of GOx. (APS-EtFc-GOx) retain more than 10% of the initial activity after forty-two successive cycles, which is a remarkable result. PMID- 26148177 TI - Chrysin-loaded PLGA-PEG nanoparticles designed for enhanced effect on the breast cancer cell line. AB - The development of nanotherapy has presented a new method of drug delivery targeted directly to the neoplasmic tissues, to maximize the action with fewer dose requirements. In the past two decades, poly(lactic-co-glycolic acid) (PLGA) has frequently been investigated by many researchers and is a popular polymeric candidate, due to its biocompatibility and biodegradability, exhibition of a wide range of erosion times, tunable mechanical properties, and most notably, because it is a FDA-approved polymer. Chrysin is a natural flavonoid which has been reported to have some significant biological effects on the processes of chemical defense, nitrogen fixation, inflammation, and oxidation. However, the low solubility in water decreases its bioavailability and consequently disrupts the biomedical benefits. Being loaded with PLGA-PEG increases chrysin solubility and drug tolerance, and decreases the discordant effects of the drug. The well structured chrysin efficiently accumulates in the breast cancer cell line (T47D). In the present study, the structure and chrysin loading were delineated using proton nuclear magnetic resonance (HNMR), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and the in vitro cytotoxicity of pure and nanochrysin was studied by the MTT assay. Next, the RNA was exploited and the cytotoxic effects of chrysin were studied by real-time PCR. In conclusion, the nanochrysin therapy developed is a novel method that could increase cytotoxicity to cancer cells without damaging the normal cells, and would be promising in breast cancer therapy. PMID- 26148178 TI - Piper betle-mediated synthesis, characterization, antibacterial and rat splenocyte cytotoxic effects of copper oxide nanoparticles. AB - The study reports a simple, inexpensive, and eco-friendly synthesis of copper oxide nanoparticles (CuONPs) using Piper betle leaf extract. Formation of CuONPs was confirmed by UV-visible spectroscopy at 280 nm. Transmission electron microscopy (TEM) images showed that the CuONPs were spherical, with an average size of 50-100 nm. The scanning electron microscopy (SEM)-energy dispersive spectroscopy (EDS) peak was observed approximately at 1 and 8 keV. The X-ray diffraction (XRD) studies indicated that the particles were crystalline in nature. CuONPs effectively inhibited the growth of phytopathogens Ralstonia solanacearum and Xanthomonas axonopodis. The cytotoxic effect of the synthesized CuONPs was analyzed using rat splenocytes. The cell viability was decreased to 94% at 300 MUg/mL. PMID- 26148179 TI - Propagation of human iPS cells in alginate-based microcapsules prepared using reactions catalyzed by horseradish peroxidase and catalase. AB - Cell encapsulation has been investigated as a bioproduction system in the biomedical and pharmaceutical fields. We encaps-ulated human induced pluripotent stem (hiPS) cells in duplex microcapsules prepared from an alginate derivative possessing phenolic hydroxyl moieties, in a single-step procedure based on two competing enzymatic reactions catalyzed by horseradish peroxidase (HRP) and catalase. The encapsulated cells maintained 91.4% viability and proliferated to fill the microcapsules following 19 days of culture. Encapsulated hiPS cells showed pluripotency comparable to that of unencapsulated cells during the cultures, as demonstrated by the expression of the SSEA-4 marker. PMID- 26148180 TI - An open-label, single-arm trial of the safety and efficacy of a novel preparation of glutathione as a skin-lightening agent in Filipino women. AB - BACKGROUND: Glutathione (GSH) is a naturally occurring thiol that has been reported to cause skin lightening in a manner for which several mechanisms have been proposed. Highest plasma concentrations are achieved with IV administration but are accompanied by greater levels of risk. Oral administration has been less successful in elevating plasma GSH levels. OBJECTIVES: The use of a lozenge containing GSH was investigated in order to evaluate the buccal mucosa as a route for GSH administration. Substances that are absorbed through the buccal route go directly into the systemic circulation, effectively bypassing the gastrointestinal tract. METHODS: Thirty Filipino females with Fitzpatrick skin types IV or V received a glutathione-containing lozenge daily for eight weeks. RESULTS: Findings showed a significant decrease in melanin indices from baseline to endpoint that became evident in as little as two weeks. There were no serious adverse events, and laboratory examination findings remained normal. CONCLUSIONS: The authors conclude that the lozenge containing glutathione was safe and effective in lightening the skin of Filipino women. PMID- 26148181 TI - Brucella infection in a child with progressive familial intrahepatic cholestasis type 2 who had undergone liver transplantation. AB - Brucellosis is considered the most widespread zoonosis in the world. In endemic regions of brucellosis, childhood brucellosis includes up to one-third of all cases of human brucellosis. Brucellosis constitutes a public health problem in Turkey. A boy aged 12 yr who had PFIC2 had undergone deceased-donor liver transplantation in 2008 at the age of seven. The boy presented with fatigue, fever, and pain in the right leg and hip and was admitted to the hospital. Brucella melitensis grew in the blood culture, and the SAT was positive at a titer of 1:640. The patient was treated with oral doxycycline and rifampicin for eight wk. After treatment, the patient recovered and his blood cultures became negative. The patient's mother also had a high Brucella agglutination titer of 1:320 positive and was treated in the internal medicine department with spiramycin and doxycycline. Brucella infection should be suspected in liver transplant recipients with fever of unknown origin, especially in recipients who live in an endemic area. PMID- 26148182 TI - Halogenated Natural Products in Dolphins: Brain-Blubber Distribution and Comparison with Halogenated Flame Retardants. AB - Halogenated natural products (MHC-1, TriBHD, TetraBHD, MeO-PBDEs, Q1, and related PMBPs) and halogenated flame retardants (PBDEs, HBB, Dec 602, Dec 603, and DP) in blubber and brain are reported from five Alboran Sea delphinids (Spain). Both HNPs and HFRs were detected in brain, implying that they are able to surpass the blood-brain barrier and reach the brain, which represents a new finding for some compounds, such as Q1 and PMBPs, MHC-1, TriBHD, TetraBHD, or Dec 603. Moreover, some compounds (TetraBHD, BDE-153, or HBB) presented higher levels in brain than in blubber. This study evidence the high concentrations of HNPs in the marine environment, especially in top predators. It shows the importance of further monitoring these natural compounds and evaluating their potential toxicity, when most studies focus on anthropogenic compounds only. While no bioaccumulation was found for ?HNPs, ?HFRs increased significantly with body size for both common and striped dolphins. Studies evaluating BBB permeation mechanisms of these compounds together with their potential neurotoxic effects in dolphins are recommended. PMID- 26148183 TI - Uneven Distribution of Cancer Histology in the National Lung Screening Trial. AB - The National Lung Screening Trial reported a 20% lower mortality due to lung cancer in the patients screened with low-dose computed tomography (LDCT) compared with plain chest radiography (XRAY). A hypothesis was raised that LDCT should detect more cases of all tissue types or else the distribution of tissue types should be equal between groups. Data were extracted regarding the tissue types of lung cancer and presenting stages from the 2011 NSLT report. A total of 1,993 cases of tissue diagnosed lung cancer were reported, 1,054 for the LDCT group and 939 for the XRAY group. Two tissue types were more prevalent in the XRAY group: small cell carcinomas (16.9% versus 13%; P < 0.05) and other non-small cell (ONSC) carcinomas (16.8% versus 12.4%; P < 0.05). The ONSC category excluded the usual non-small cell tissue types: adenocarcinomas, squamous, and large cell carcinomas and did include other known biologically unfavorable tissue types. The XRAY group also had a disproportionately large number of stage IV small cell and ONSC tumors (P < 0.05 for ONSC). Bronchoalveolar cell carcinomas were more prevalent in the LDCT group (10.4% versus 3.7%, P < 0.05), likely reflecting greater sensitivity for detection. In summary, this review found uneven distribution of cases and higher preponderance of stage IV tumors for 2 adverse tissue types in the XRAY group. The results are consistent with greater severity of disease in the XRAY group with potential for length time bias and reduced mortality benefit from LDCT screening. PMID- 26148184 TI - Didymosphenia geminata in the Upper Esopus Creek: Current Status, Variability, and Controlling Factors. AB - In May of 2009, the bloom-forming diatom Didymosphenia geminata was first identified in the Upper Esopus Creek, a key tributary to the New York City water supply and a popular recreational stream. The Upper Esopus receives supplemental flows from the Shandaken Portal, an underground aqueduct delivering waters from a nearby basin. The presence of D. geminata is a concern for the local economy, water supply, and aquatic ecosystem because nuisance blooms have been linked to degraded stream condition in other regions. Here we ascertain the extent and severity of the D. geminata invasion, determine the impact of supplemental flows from the Portal on D. geminata, and identify potential factors that may limit D. geminata in the watershed. Stream temperature, discharge, and water quality were characterized at select sites and periphyton samples were collected five times at 6 to 20 study sites between 2009 and 2010 to assess standing crop, diatom community structure, and density of D. geminata and all diatoms. Density of D. geminata ranged from 0-12 cells cm(-2) at tributary sites, 0-781 cells cm(-2) at sites upstream of the Portal, and 0-2,574 cells cm(-2) at sites downstream of the Portal. Survey period and Portal (upstream or downstream) each significantly affected D. geminata cell density. In general, D. geminata was most abundant during the November 2009 and June 2010 surveys and at sites immediately downstream of the Portal. We found that D. geminata did not reach nuisance levels or strongly affect the periphyton community. Similarly, companion studies showed that local macroinvertebrate and fish communities were generally unaffected. A number of abiotic factors including variable flows and moderate levels of phosphorous and suspended sediment may limit blooms of D. geminata in this watershed. PMID- 26148185 TI - A 1H-NMR Based Study on Hemolymph Metabolomics in Eri Silkworm after Oral Administration of 1-Deoxynojirimycin. AB - We aimed to investigate whether 1-deoxynojirimycin (DNJ) modulates glycometabolism and has toxicity in Eri silkworm (Samia cynthia ricini, Saturniidae). In this paper, hemolymph metabolites were used to explore metabolic changes after oral administration of DNJ or mulberry latex and to characterize the biological function of DNJ at the metabolic and systemic levels. Hemolymph samples were collected from fourth-instar larvae of Eri silkworm and ex-vivo high resolution 1H nuclear magnetic resonance (NMR) spectra were acquired from the collected hemolymph samples. Then the obtained spectra were analyzed by principal component analysis (PCA) and independent-samples t-test. Metabolic pattern recognition analysis of hemolymph samples indicated that the groups of 0.25% DNJ, latex, and the mixture of 0.5% DNJ and latex (1:1) were significantly different from the control group. Moreover, compared to the control group, the groups of 0.25% DNJ, latex, and the mixture of 0.5% DNJ and latex (1:1) showed the decreased levels of citrate, succinate, fumarate, malate, and glutamine in hemolymph, the groups of 0.25% DNJ and the mixture of 0.5% DNJ and latex (1:1) showed the increased levels of trehalose and lactate. In addition, mulberry leaves exude latex was highly toxic to Eri silkworm because rich unidentified high-molecular-weight factor (s) acted as toxic substances. In our results, latex caused 20 deaths among 50 fourth-instar larvae of Eri silkmoth, but DNJ or the mixture did not caused death. All these results suggest that DNJ has a positive impact on the reverse glycometabolism by modulating glycometabolism and inhibiting glucogenesis and energy metabolism. DNJ is a secure substance as a single-ingredient antidiabetic medicine due to its nontoxicity and bioactivity. PMID- 26148187 TI - Habitual exercise instigation (vs. execution) predicts healthy adults' exercise frequency. AB - OBJECTIVE: Habit is thought to be conducive to health behavior maintenance, because habits prompt behavior with minimal cognitive resources. The precise role of habit in determining complex behavioral sequences, such as exercise, has been underresearched. It is possible that the habit process may initiate a behavioral sequence (instigation habit) or that, after instigation, movement through the sequence is automated (execution habit). We hypothesized that exercise instigation habit can be empirically distinguished from exercise execution habit and that instigation habit strength is most predictive of future exercise and reflective of longitudinal exercise behavior change. Further, we evaluated whether patterned exercise action-that is, engaging in the same exercise actions from session to session-can be distinct from exercise execution habit. METHOD: Healthy adults (N = 123) rated their exercise instigation and execution habit strengths, patterned exercise actions, and exercise frequency in baseline and 1 month follow-up surveys. Participants reported exercise engagement via electronic daily diaries for 1 month. Hypotheses were tested with regression analyses and repeated-measures analyses of variance. RESULTS: Exercise instigation habit strength was the only unique predictor of exercise frequency. Frequency profiles (change from high to low or low to high, no change high, no change low) were associated with changes in instigation habit but not with execution habit or patterned exercise action. CONCLUSIONS: Results suggest that the separable components of exercise sessions may be more or less automatic, and they point to the importance of developing instigation habit for establishing frequent exercise. PMID- 26148186 TI - A Potent Inhibitor of Phosphoinositide 3-Kinase (PI3K) and Mitogen Activated Protein (MAP) Kinase Signalling, Quercetin (3, 3', 4', 5, 7-Pentahydroxyflavone) Promotes Cell Death in Ultraviolet (UV)-B-Irradiated B16F10 Melanoma Cells. AB - Ultraviolet (UV) radiation-induced skin damage contributes strongly to the formation of melanoma, a highly lethal form of skin cancer. Quercetin (Qu), the most widely consumed dietary bioflavonoid and well known inhibitor of phosphoinositide 3-kinase (PI3K) and mitogen activated protein (MAP) kinase signalling, has been reported to be chemopreventive in several forms of non melanoma skin cancers. Here, we report that the treatment of ultraviolet (UV)-B irradiated B16F10 melanoma cells with quercetin resulted in a dose dependent reduction in cell viability and increased apoptosis. The present study has brought out that the pro-apoptotic effects of quercetin in UVB-irradiated B16F10 cells are mediated through the elevation of intracellular reactive oxygen species (ROS) formation, calcium homeostasis imbalance, modulation of anti-oxidant defence response and depolarization of mitochondrial membrane potential (DeltaPsiM). Promotion of UVB-induced cell death by quercetin was further revealed by cleavage of chromosomal DNA, caspase activation, poly (ADP) ribose polymerase (PARP) cleavage, and an increase in sub-G1 cells. Quercetin markedly attenuated MEK-ERK signalling, influenced PI3K/Akt pathway, and potentially enhanced the UVB-induced NF-kappaB nuclear translocation. Furthermore, combined UVB and quercetin treatment decreased the ratio of Bcl-2 to that of Bax, and upregulated the expression of Bim and apoptosis inducing factor (AIF). Overall, these results suggest the possibility of using quercetin in combination with UVB as a possible treatment option for melanoma in future. PMID- 26148188 TI - Understanding African American college students' H1N1 vaccination decisions. AB - OBJECTIVE: In this study, we examined the effects of cognitive appraisals and individual differences in discomfort with uncertainty, as measured by a short form of Webster and Kruglanski's (1994) Need for Closure (NFC) scale, on African American college students' self-reported H1N1 vaccination decisions during the 2009-2010 H1N1 pandemic. METHOD: Howard University undergraduates, who self identified as Black or African American and met U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC) H1N1 high priority group criteria, completed computer-administered surveys that included (a) questions about H1N1 vaccination status; self-efficacy; perceived costs, benefits, and efficaciousness of the H1N1 vaccine; and potential barriers to vaccination, including flu-shot frequency; (b) demographic measures; and (c) a short form of Kruglanski's NFC scale (Orehek et al., 2010). RESULTS: A sequential multinomial logistic regression revealed (a) a significant effect of NFC on vaccination status such that higher NFC was associated with lower odds of being vaccinated or intending to be vaccinated, after controlling for demographic variables, comfort with flu vaccinations more generally, and several other potential vaccination barriers, chi(2)(2, 217) = 10.08, p = .006; and (b) vaccination status was best accounted for by a model that included perceptions of the vaccine's costs, benefits, and efficaciousness, and participants' self efficacy for being vaccinated, chi(2)(6, 217) = 57.24, p < .001. CONCLUSION: Our data suggest the importance of cognitive appraisals and traits (i.e., comfort with uncertainty) in the process individuals use to make potentially life-saving vaccination decisions. PMID- 26148189 TI - "It's sort of a lifeline": Chronic obstructive pulmonary disease patients' experiences of home telehealth. AB - OBJECTIVE: Home telehealth can provide considerable benefits to people diagnosed with chronic obstructive pulmonary disease, yet 20% of patients abandon telehealth. Identifying the factors that affect whether or not a patient decides to continue using telehealth is therefore crucial to the goal of mainstreaming telehealth. However, studies to date have only assessed the perceptions of patients who are not currently using telehealth, have used telehealth in experimental sessions, or are enrolled in a trial. The aim of the present study was to explore the beliefs and perceptions of patients with chronic obstructive pulmonary disease currently using home telehealth and who are not enrolled in a trial. METHOD: Semistructured interviews were conducted with 8 patients with chronic obstructive pulmonary disease. Interviews were analyzed using interpretative phenomenological analysis. RESULTS: Four superordinate themes are presented: (a) perceiving benefits of "being watched over" as providing peace of mind, (b) learning about the health condition and the impacts on self-management behavior, (c) active engagement in health service provision and better access to health care, and (d) valuing the importance of in-person care. CONCLUSIONS: Users generally describe home telehealth in positive terms; however, patients still value face-to-face contact with health care professionals. The positive aspects of home telehealth, such as better access to health care and providing peace of mind, could be communicated to prospective users to improve uptake. Similarly, sustained use of telehealth is likely to be ensured if occasional visits from health care professionals are maintained. PMID- 26148190 TI - Rule-Based Design of Plant Expression Vectors Using GenoCAD. AB - Plant synthetic biology requires software tools to assist on the design of complex multi-genic expression plasmids. Here a vector design strategy to express genes in plants is formalized and implemented as a grammar in GenoCAD, a Computer Aided Design software for synthetic biology. It includes a library of plant biological parts organized in structural categories and a set of rules describing how to assemble these parts into large constructs. Rules developed here are organized and divided into three main subsections according to the aim of the final construct: protein localization studies, promoter analysis and protein protein interaction experiments. The GenoCAD plant grammar guides the user through the design while allowing users to customize vectors according to their needs. Therefore the plant grammar implemented in GenoCAD will help plant biologists take advantage of methods from synthetic biology to design expression vectors supporting their research projects. PMID- 26148191 TI - Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells. AB - Chemotherapy resistance is the major reason for the failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves the upregulation of multidrug resistance (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out of the tumor cells. As a common symptom in stage III/IV ovarian cancer patients, ascites is associated with cancer progression. However, whether ascites drives multidrug resistance in ovarian cancer cells awaits elucidation. Here, we demonstrate that when cultured with ascites derived from ovarian cancer-bearing mice, a murine ovarian cancer cell line became less sensitive to paclitaxel, a first line chemotherapeutic agent for ovarian cancer patients. Moreover, incubation of murine ovarian cancer cells in vitro with ascites drives efflux function in these cells. Functional studies show ascites driven efflux is suppressible by specific inhibitors of either of two ABC transporters [Multidrug Related Protein (MRP1); Breast Cancer Related Protein (BCRP)]. To demonstrate relevance of our findings to ovarian cancer patients, we studied relative efflux in human ovarian cancer cells obtained from either patient ascites or from primary tumor. Immortalized cell lines developed from human ascites show increased susceptibility to efflux inhibitors (MRP1, BCRP) compared to a cell line derived from a primary ovarian cancer, suggesting an association between ascites and efflux function in human ovarian cancer. Efflux in ascites-derived human ovarian cancer cells is associated with increased expression of ABC transporters compared to that in primary tumor-derived human ovarian cancer cells. Collectively, our findings identify a novel activity for ascites in promoting ovarian cancer multidrug resistance. PMID- 26148193 TI - Basic Emotions in the Nencki Affective Word List (NAWL BE): New Method of Classifying Emotional Stimuli. AB - The Nencki Affective Word List (NAWL) has recently been introduced as a standardized database of Polish words suitable for studying various aspects of language and emotions. Though the NAWL was originally based on the most commonly used dimensional approach, it is not the only way of studying emotions. Another framework is based on discrete emotional categories. Since the two perspectives are recognized as complementary, the aim of the present study was to supplement the NAWL database by the addition of categories corresponding to basic emotions. Thus, 2902 Polish words from the NAWL were presented to 265 subjects, who were instructed to rate them according to the intensity of each of the five basic emotions: happiness, anger, sadness, fear and disgust. The general characteristics of the present word database, as well as the relationships between the studied variables are shown to be consistent with typical patterns found in previous studies using similar databases for different languages. Here we present the Basic Emotions in the Nencki Affective Word List (NAWL BE) as a database of verbal material suitable for highly controlled experimental research. To make the NAWL more convenient to use, we introduce a comprehensive method of classifying stimuli to basic emotion categories. We discuss the advantages of our method in comparison to other methods of classification. Additionally, we provide an interactive online tool (http://exp.lobi.nencki.gov.pl/nawl-analysis) to help researchers browse and interactively generate classes of stimuli to meet their specific requirements. PMID- 26148192 TI - High Accuracy of Common HIV-Related Oral Disease Diagnoses by Non-Oral Health Specialists in the AIDS Clinical Trial Group. AB - OBJECTIVE: Many studies include oral HIV-related endpoints that may be diagnosed by non-oral-health specialists (non-OHS) like nurses or physicians. Our objective was to assess the accuracy of clinical diagnoses of HIV-related oral lesions made by non-OHS compared to diagnoses made by OHS. METHODS: A5254, a cross-sectional study conducted by the Oral HIV/AIDS Research Alliance within the AIDS Clinical Trial Group, enrolled HIV-1-infected adults participants from six clinical trial units (CTU) in the US (San Francisco, New York, Chapel Hill, Cleveland, Atlanta) and Haiti. CTU examiners (non-OHS) received standardized training on how to perform an oral examination and make clinical diagnoses of specific oral disease endpoints. Diagnoses by calibrated non-OHS were compared to those made by calibrated OHS, and sensitivity and specificity computed. RESULTS: Among 324 participants, the majority were black (73%), men (66%), and the median CD4+ cell count 138 cells/mm(3). The overall frequency of oral mucosal disease diagnosed by OHS was 43% in US sites, and 90% in Haiti. Oral candidiasis (OC) was detected in 153 (47%) by OHS, with erythematous candidiasis (EC) the most common type (39%) followed by pseudomembranous candidiasis (PC; 26%). The highest prevalence of OC (79%) was among participants in Haiti, and among those with CD4+ cell count <= 200 cells/mm(3) and HIV-1 RNA > 1000 copies/mL (71%). The sensitivity and specificity of OC diagnoses by non-OHS were 90% and 92% (for EC: 81% and 94%; PC: 82% and 95%). Sensitivity and specificity were also high for KS (87% and 94%, respectively), but sensitivity was < 60% for HL and oral warts in all sites combined. The Candida culture confirmation of OC clinical diagnoses (as defined by >= 1 colony forming unit per mL of oral/throat rinse) was >= 93% for both PC and EC. CONCLUSION: Trained non-OHS showed high accuracy of clinical diagnoses of OC in comparison with OHS, suggesting their usefulness in studies in resource poor settings, but detection of less common lesions may require OHS. PMID- 26148194 TI - Linking Colleague Support to Employees' Promotive Voice: A Moderated Mediation Model. AB - Promotive voice is essential for improving team and organization performance. Yet in the current literature, less was known regarding the psychological reasons why people engage in promotive voice. Through the lens of social exchange, we proposed that employees who received support from colleagues may develop higher level of felt obligation for constructive change which leads to promotive voice. Analyses of multi-source data from 51 cross-functional sources (51 team supervisors and 162 employees) showed that employees' felt obligation for constructive change positively mediates the relationship between colleague support and promotive voice behavior. Moreover, the impact of colleague support on felt obligation for constructive change is stronger when there is a low level of subgroup formation in the team. Theoretical and practical implications of these findings are discussed. PMID- 26148196 TI - Robust and Ultrasensitive Polymer Membrane-Based Carbonate-Selective Electrodes. AB - Quantitative analysis of the carbonate species within clinical and environmental samples is highly critical to the advancement of accurate environmental monitoring, disease screening, and personalized medicine. Herein we report the first example of carbonate detection using ultrasensitive ion selective electrodes (ISEs). The low detection limit (LDL) of these electrodes was at least 4 orders of magnitude lower than the best currently existing carbonate sensors. This was achieved by a simple alteration of the sensor's conditioning protocol. This resulted in the reduction of ion fluxes across the membrane interface consequently lowering the LDL to picomolar levels. The proposed ISEs exhibited near-Nernstian potentiometric responses to carbonate ions with a detection limit of 80 pmol L(-1) (5 ppt) and was utilized for direct determination of carbonate in seawater. Moreover, the new methodology has produced electrodes with excellent reproducibility, robustness, and durability. It is anticipated that this approach may form the basis for the development of highly sensitive and robust ion selective electrodes capable of in situ measurements. PMID- 26148195 TI - Status Epilepticus Induced Spontaneous Dentate Gyrus Spikes: In Vivo Current Source Density Analysis. AB - The dentate gyrus is considered to function as an inhibitory gate limiting excitatory input to the hippocampus. Following status epilepticus (SE), this gating function is reduced and granule cells become hyper-excitable. Dentate spikes (DS) are large amplitude potentials observed in the dentate gyrus (DG) of normal animals. DS are associated with membrane depolarization of granule cells, increased activity of hilar interneurons and suppression of CA3 and CA1 pyramidal cell firing. Therefore, DS could act as an anti-excitatory mechanism. Because of the altered gating function of the dentate gyrus following SE, we sought to investigate how DS are affected following pilocarpine-induced SE. Two weeks following lithium-pilocarpine SE induction, hippocampal EEG was recorded in male Sprague-Dawley rats with 16-channel silicon probes under urethane anesthesia. Probes were placed dorso-ventrally to encompass either CA1-CA3 or CA1-DG layers. Large amplitude spikes were detected from EEG recordings and subject to current source density analysis. Probe placement was verified histologically to evaluate the anatomical localization of current sinks and the origin of DS. In 9 of 11 pilocarpine-treated animals and two controls, DS were confirmed with large current sinks in the molecular layer of the dentate gyrus. DS frequency was significantly increased in pilocarpine-treated animals compared to controls. Additionally, in pilocarpine-treated animals, DS displayed current sinks in the outer, middle and/or inner molecular layers. However, there was no difference in the frequency of events when comparing between layers. This suggests that following SE, DS can be generated by input from medial and lateral entorhinal cortex, or within the dentate gyrus. DS were associated with an increase in multiunit activity in the granule cell layer, but no change in CA1. These results suggest that following SE there is an increase in DS activity, potentially arising from hyperexcitability along the hippocampal-entorhinal pathway or within the dentate gyrus itself. PMID- 26148197 TI - Observed child and parent toothbrushing behaviors and child oral health. AB - BACKGROUND: Parent-led toothbrushing effectively reduces early childhood caries. Research on the strategies that parents use to promote this behavior is, however, lacking. AIM: To examine associations between parent-child toothbrushing interactions and child oral health using a newly developed measure, the Toothbrushing Observation System (TBOS). DESIGN: One hundred children ages 18-60 months and their parents were video-recorded during toothbrushing interactions. Using these recordings, six raters coded parent and child behaviors and the duration of toothbrushing. We examined the reliability of the coding system and associations between observed parent and child behaviors and three indices of oral health: caries, gingival health, and history of dental procedures requiring general anesthesia. RESULTS: Reliabilities were moderate to strong for TBOS child and parent scores. Parent TBOS scores and longer duration of parent-led toothbrushing were associated with fewer decayed, missing or filled tooth surfaces and lower incidence of gingivitis and procedures requiring general anesthesia. Associations between child TBOS scores and dental outcomes were modest, suggesting the relative importance of parent versus child behaviors at this early age. CONCLUSIONS: Parents' child behavior management skills and the duration of parent-led toothbrushing were associated with better child oral health. These findings suggest that parenting skills are an important target for future behavioral oral health interventions. PMID- 26148198 TI - The Rat Homolog of the Schizophrenia Susceptibility Gene ZNF804A Is Highly Expressed during Brain Development, Particularly in Growth Cones. AB - A single nucleotide polymorphism in the ZNF804A gene, rs1344706, is associated with schizophrenia. The polymorphism has been suggested to alter fetal expression of ZNF804A. It has also been reported to be associated with altered cortical functioning and neural connectivity in the brain. Since developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after it decreases towards adult levels. This time point is developmentally the equivalent to the second trimester of fetal development in humans. An exception to this expression pattern is the hippocampus where the expression of Zfp804A appears to increase again in the adult brain. Using laser capture and quantitative PCR we found that Zfp804A mRNA expression in the adult rat hippocampus is highest in the CA1 sub region, where the overall firing rates of neurons is higher than in the CA3 region. In cultured cortical neurons Zfp804A mRNA expression peaked at day 4 and then decreased. The ZFP804A protein expression was therefore investigated with immunochemistry in such cultures. Interestingly, before day 4, the protein is mostly found in the perinuclear region of the cell but at day 4, ZFP804A was instead found throughout the cell and particularly in the growth cones. In conclusion we demonstrate that Zfp804A increases in the rat brain at the time of birth, coinciding with neuronal differentiation. We also show that ZFP804A is localized to growth cones of growing neurites. These data implicate ZFP804A in growth cone function and neurite elongation. The polymorphism rs1344706 lowers expression of ZNF804A during prenatal brain development. This may affect ZNF804A's role in cone function and neurite elongation leading to synaptic deficits and altered neural connectivity. PMID- 26148199 TI - Concerns with performance of screening for aneuploidy by cell-free DNA analysis of maternal blood in twin pregnancy. PMID- 26148201 TI - Evaluation of Flibanserin: Science and Advocacy at the FDA. PMID- 26148200 TI - Neurodegeneration and Vision Loss after Mild Blunt Trauma in the C57Bl/6 and DBA/2J Mouse. AB - Damage to the eye from blast exposure can occur as a result of the overpressure air-wave (primary injury), flying debris (secondary injury), blunt force trauma (tertiary injury), and/or chemical/thermal burns (quaternary injury). In this study, we investigated damage in the contralateral eye after a blast directed at the ipsilateral eye in the C57Bl/6J and DBA/2J mouse. Assessments of ocular health (gross pathology, electroretinogram recordings, optokinetic tracking, optical coherence tomography and histology) were performed at 3, 7, 14 and 28 days post-trauma. Olfactory epithelium and optic nerves were also examined. Anterior pathologies were more common in the DBA/2J than in the C57Bl/6 and could be prevented with non-medicated viscous eye drops. Visual acuity decreased over time in both strains, but was more rapid and severe in the DBA/2J. Retinal cell death was present in approximately 10% of the retina at 7 and 28 days post-blast in both strains. Approximately 60% of the cell death occurred in photoreceptors. Increased oxidative stress and microglial reactivity was detected in both strains, beginning at 3 days post-injury. However, there was no sign of injury to the olfactory epithelium or optic nerve in either strain. Although our model directs an overpressure air-wave at the left eye in a restrained and otherwise protected mouse, retinal damage was detected in the contralateral eye. The lack of damage to the olfactory epithelium and optic nerve, as well as the different timing of cell death as compared to the blast-exposed eye, suggests that the injuries were due to physical contact between the contralateral eye and the housing chamber of the blast device and not propagation of the blast wave through the head. Thus we describe a model of mild blunt eye trauma. PMID- 26148202 TI - Milnacipran for neuropathic pain in adults. AB - BACKGROUND: Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is sometimes used to treat chronic neuropathic pain and fibromyalgia. This is an update of an earlier review of milnacipran for neuropathic pain and fibromyalgia in adults originally published in The Cochrane Library Issue 3, 2012. We split that review so that this one looked only at neuropathic pain, and a separate review looks at fibromyalgia. OBJECTIVES: To assess the analgesic efficacy and associated adverse events of milnacipran for chronic neuropathic pain in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to 23 February 2015, together with reference lists of retrieved papers and reviews. SELECTION CRITERIA: We included randomised, double-blind studies of eight weeks' duration or longer, comparing milnacipran with placebo or another active treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality. We did not carry out any analysis. MAIN RESULTS: We included a single study of 40 participants with chronic low back pain with a neuropathic component. It found no difference in pain scores between milnacipran 100 mg to 200 mg daily or placebo after six weeks (very low quality evidence). Adverse event rates were similar between treatments, with too few data to draw conclusions (very low quality evidence). AUTHORS' CONCLUSIONS: There was no evidence to support the use of milnacipran to treat neuropathic pain conditions. PMID- 26148203 TI - De Novo Transcriptome Assembly and Identification of Gene Candidates for Rapid Evolution of Soil Al Tolerance in Anthoxanthum odoratum at the Long-Term Park Grass Experiment. AB - Studies of adaptation in the wild grass Anthoxanthum odoratum at the Park Grass Experiment (PGE) provided one of the earliest examples of rapid evolution in plants. Anthoxanthum has become locally adapted to differences in soil Al toxicity, which have developed there due to soil acidification from long-term experimental fertilizer treatments. In this study, we used transcriptome sequencing to identify Al stress responsive genes in Anthoxanhum and identify candidates among them for further molecular study of rapid Al tolerance evolution at the PGE. We examined the Al content of Anthoxanthum tissues and conducted RNA sequencing of root tips, the primary site of Al induced damage. We found that despite its high tolerance Anthoxanthum is not an Al accumulating species. Genes similar to those involved in organic acid exudation (TaALMT1, ZmMATE), cell wall modification (OsSTAR1), and internal Al detoxification (OsNRAT1) in cultivated grasses were responsive to Al exposure. Expression of a large suite of novel loci was also triggered by early exposure to Al stress in roots. Three-hundred forty five transcripts were significantly more up- or down-regulated in tolerant vs. sensitive Anthoxanthum genotypes, providing important targets for future study of rapid evolution at the PGE. PMID- 26148205 TI - Chronic active Epstein-Barr virus infection with cutaneous and sinus lymphoproliferation in a white female patient with 25 years' follow-up: an original case report. AB - Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms associated with very high viral load, as assessed by quantitative polymerase chain reaction. We present an unusual case in a French woman who was followed up over 25 years with cutaneous and sinus lymphoproliferation. This white woman presented with a long history of recurrent cutaneous necrotic papules of the skin, which started during childhood and healed spontaneously with depressed scars. The lesions spread to the left maxillary sinus and were associated with hepatomegaly and splenomegaly with no other visceral locations. Pathological examination of the skin and sinus revealed a dermal monoclonal T-cell lymphoproliferative disorder, CD7(+) and CD20(-) , with no epidermotropism. T-cell receptor rearrangement was positive, showing the monoclonality from the first biopsy. This T-cell proliferation was positive for EBV-encoded small RNA and was associated with a high EBV viral load. Since then, the patient has been in good health, despite a permanently high EBV viral load. Hydroa vacciniforme (HV)-like lymphoma and natural killer/T-cell lymphoma were discussed, but none really fit our case. Natural killer cell lymphoma was ruled out because of the indolent course, but sinus lesions do not exist in HV-like lymphoma. A therapeutic approach is difficult because of the coexistence of viral infection and monoclonal T-cell proliferation. Chemotherapy is not efficient and induces immunosuppression, which may worsen the prognosis. Although rituximab may have an immunomodulatory function, it was not effective in our case. PMID- 26148206 TI - DUOX-Mediated Signaling Is Not Required for LPS-Induced Neutrophilic Response in the Airways. AB - Oxidant production from DUOX1 has been proposed to lead to neutrophil recruitment into the airways when lung homeostasis is compromised. The objective of this study was to determine whether DUOX-derived hydrogen peroxide is required for LPS induced neutrophil recruitment, using a functional DUOX knock out mouse model. We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h. Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-alpha) between the two groups. These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium. PMID- 26148204 TI - Genomewide association study of tenofovir pharmacokinetics and creatinine clearance in AIDS Clinical Trials Group protocol A5202. AB - BACKGROUND: Tenofovir disoproxil fumarate (TDF) causes kidney toxicity in some patients. We carried out genomewide analyses to identify associations with plasma tenofovir clearance and change in creatinine clearance (CrCl) during the first 6 months after initiating therapy among patients randomized to TDF/emtricitabine containing regimens in AIDS Clinical Trials Group protocol A5202. METHODS: Pharmacokinetic analyses involved 501 patients randomized to the tenofovir arm. CrCl analyses involved 1096 patients, including 548 controls randomized to abacavir-containing regimens. All had been randomized to also receive atazanavir/ritonavir or efavirenz. Multivariable linear regression and generalized least squares models were used to test for associations between polymorphisms and tenofovir clearance and CrCl change, with Bonferroni correction. Planned subanalyses considered candidate genes and polymorphisms. RESULTS: Median CrCl at baseline was 116 ml/min (interquartile range 99.8-135.5). The median change in CrCl after 6 months was -0.5 ml/min (-10.7 to +10.8) and 2.2 (interquartile range -9.9 to +13.2) in tenofovir and abacavir arms, respectively. In genomewide analyses SLC17A1 rs12662869 was found to be associated with an increase in tenofovir clearance (P=7.1*10). In candidate gene analysis for tenofovir clearance, most polymorphisms evaluated were in ABCC4. In the ABCC4 region, the lowest P-value was for CLDN10 rs12866697 (P=1.4*10). Among African Americans, SLC22A2 rs3127573 was associated with a greater 6-month CrCl increase in the tenofovir arm after correcting for multiple comparisons (P=3.3*10). CONCLUSION: Among patients randomized to receive TDF/emtricitabine in A5202, there were no significant genomewide associations with change in CrCl. This study did not replicate polymorphisms previously implicated in tenofovir-associated renal injury. PMID- 26148207 TI - The Cytotoxicity of Elderberry Ribosome-Inactivating Proteins Is Not Solely Determined by Their Protein Translation Inhibition Activity. AB - Although the protein translation inhibition activity of ribosome inactivating proteins (RIPs) is well documented, little is known about the contribution of the lectin chain to the biological activity of these proteins. In this study, we compared the in vitro and intracellular activity of several S. nigra (elderberry) RIPs and non-RIP lectins. Our data demonstrate that RIPs from elderberry are much more toxic to HeLa cells than to primary fibroblasts. Differences in the cytotoxicity between the elderberry proteins correlated with differences in glycan specificity of their lectin domain, cellular uptake efficiency and intracellular destination. Despite the fact that the bulk of the RIPs accumulated in the lysosomes and partly in the Golgi apparatus, we could demonstrate effective inhibition of protein synthesis in cellula. As we also observed cytotoxicity for non-RIP lectins, it is clear that the lectin chain triggers additional pathways heralding cell death. Our data suggest that one of these pathways involves the induction of autophagy. PMID- 26148208 TI - Quantum Chemical Simulation of Carbon Nanotube Nucleation on Al2O3 Catalysts via CH4 Chemical Vapor Deposition. AB - We present quantum chemical simulations demonstrating how single-walled carbon nanotubes (SWCNTs) form, or "nucleate", on the surface of Al2O3 nanoparticles during chemical vapor deposition (CVD) using CH4. SWCNT nucleation proceeds via the formation of extended polyyne chains that only interact with the catalyst surface at one or both ends. Consequently, SWCNT nucleation is not a surface mediated process. We demonstrate that this unusual nucleation sequence is due to two factors. First, the pi interaction between graphitic carbon and Al2O3 is extremely weak, such that graphitic carbon is expected to desorb at typical CVD temperatures. Second, hydrogen present at the catalyst surface actively passivates dangling carbon bonds, preventing a surface-mediated nucleation mechanism. The simulations reveal hydrogen's reactive chemical pathways during SWCNT nucleation and that the manner in which SWCNTs form on Al2O3 is fundamentally different from that observed using "traditional" transition metal catalysts. PMID- 26148210 TI - Sexual Functioning in Young Women and Men: Role of Attachment Orientation. AB - Prior research has documented various ways in which adult attachment styles are characteristic of differential behavioral and cognitive patterns within romantic relationships and sexuality. However, few studies have examined the direct influence of anxious or avoidant attachment orientation on sexual function. The aim of the present study was to assess the impact of insecure attachment on sexual function. Undergraduate students completed questionnaires measuring attachment style and sexual functioning. Among women, attachment avoidance tended to be associated with impairments in all aspects of sexual function, whereas anxious attachment tended to be associated with declines in arousal, satisfaction, and ability to achieve orgasm. A different trend was seen in men: Anxious attachment tended to be associated with multiple facets of sexual dysfunction, while avoidant attachment did not correlate with any sexual function deficits and was associated with superior physiological competence. These results suggest that both anxious and avoidant attachment styles are important yet differential predictors of sexual function in men and women. PMID- 26148209 TI - Revisiting the Diego Blood Group System in Amerindians: Evidence for Gene-Culture Comigration. AB - Six decades ago the DI*A allele of the Diego blood group system was instrumental in proving Native American populations originated from Siberia. Since then, it has received scant attention. The present study was undertaken to reappraise distribution of the DI*A allele in 144 Native American populations based on current knowledge. Using analysis of variance tests, frequency distribution was studied according to geographical, environmental, and cultural parameters. Frequencies were highest in Amazonian populations. In contrast, DI*A was undetectable in subarctic, Fuegian, Panamanian, Chaco and Yanomama populations. Closer study revealed a correlation that this unequal distribution was correlated with language, suggesting that linguistic divergence was a driving force in the expansion of DI*A among Native Americans. The absence of DI*A in circumpolar Eskimo-Aleut and Na-Dene speakers was consistent with a late migratory event confined to North America. Distribution of DI*A in subtropical areas indicated that gene and culture exchanges were more intense within than between ecozones. Bolstering the utility of classical genetic markers in biological anthropology, the present study of the expansion of Diego blood group genetic polymorphism in Native Americans shows strong evidence of gene-culture comigration. PMID- 26148211 TI - A Graphene-like Oxygenated Carbon Nitride Material for Improved Cycle-Life Lithium/Sulfur Batteries. AB - Novel sulfur (S) anchoring materials and the corresponding mechanisms for suppressing capacity fading are urgently needed to advance the performance of Li/S batteries. Here, we designed and synthesized a graphene-like oxygenated carbon nitride (OCN) host material that contains tens of micrometer scaled two dimensional (2D) rippled sheets, micromesopores, and oxygen heteroatoms. N content can reach as high as 20.49 wt %. A sustainable approach of one-step self supporting solid-state pyrolysis (OSSP) was developed for the low-cost and large scale production of OCN. The urea in solid sources not only provides self supporting atmospheres but also produces graphitic carbon nitride (g-C3N4) working as 2D layered templates. The S/OCN cathode can deliver a high specific capacity of 1407.6 mA h g(-1) at C/20 rate with 84% S utilization and retain improved reversible capacity during long-term cycles at high current density. The increasing micropores, graphitic N, ether, and carboxylic O at the large sized OCN sheet favor S utilization and trapping for polysulfides. PMID- 26148212 TI - Responses to a 120 min reserve team soccer match: a case study focusing on the demands of extra time. AB - The movement demands of the soccer extra time period are unknown despite the importance of this period of play. Data are presented for five English Premier League reserve team players who wore GPS (10 Hz) monitors during an official soccer match that required extra time to be played. Countermovement jump performance (peak power output (PPO) and jump height) and creatine kinase (CK) concentrations were assessed before (-24 h; baseline) and after (+24 h, +48 h) match play. Players covered 14,106 +/- 859 m (109 +/- 7 m.min(-1)) throughout the game. From 90 to 120 min, 3213 +/- 286 m were covered and 12 +/- 6 sprints, 221 +/- 14 accelerations and 207 +/- 16 decelerations occurred. From 105 to 120 min, acceleration and deceleration parameters reduced by >10% compared to the opening 15 min. At +24 h and +48 h, PPO reduced by 416.1 +/- 199.9 W (10.9% +/- 4.4%) and 155.1 +/- 34.8 W (4.1% +/- 0.8%), jump heights decreased by 0.064 +/- 0.046 m (17.8% +/- 11.2%) and 0.025 +/- 0.009 m (7.4% +/- 3.2%), whereas CK increased by 586.6 +/- 85.1 MU.l(-1) (236% +/- 92%) and 266.8 +/- 134.7 MU.l(-1) (107% +/- 89%) versus baseline, respectively. Physical performance markers reduced throughout match play and countermovement jump performance was impaired, while CK remained elevated, for at least 48 h after the game. Interventions which maintain performance throughout a game and which enhance recovery in the days after 120 min of soccer match play warrant further investigation. PMID- 26148213 TI - Organizational impact of nurse supply and workload on nurses continuing professional development opportunities: an integrative review. AB - AIM: To identify the best evidence on the impact of healthcare organizations' supply of nurses and nursing workload on the continuing professional development opportunities of Registered Nurses in the acute care hospital. BACKGROUND: To maintain registration and professional competence nurses are expected to participate in continuing professional development. One challenge of recruitment and retention is the Registered Nurse's ability to participate in continuing professional development opportunities. DESIGN: The integrative review method was used to present Registered Nurses perspectives on this area of professional concern. DATA SOURCES: The review was conducted for the period of 2001-February 2015. Keywords were: nurs*, continuing professional development, continuing education, professional development, supply, shortage, staffing, workload, nurse: patient ratio, barrier and deterrent. REVIEW METHODS: The integrative review used a structured approach for literature search and data evaluation, analysis and presentation. Eleven international studies met the inclusion criteria. RESULTS: Nurses are reluctant or prevented from leaving clinical settings to attend continuing professional development due to lack of relief cover, obtaining paid or unpaid study leave, use of personal time to undertake mandatory training and organizational culture and leadership issues constraining the implementation of learning to benefit patients. CONCLUSION: Culture, leadership and workload issues impact nurses' ability to attend continuing professional development. The consequences affect competence to practice, the provision of safe, quality patient care, maintenance of professional registration, job satisfaction, recruitment and retention. Organizational leadership plays an important role in supporting attendance at continuing professional development as an investment for the future. PMID- 26148214 TI - Commentary: Status of road safety in Asia. AB - OBJECTIVES: The objective of this article is to assess the status of road safety in Asia and present accident and injury prevention strategies based on global road safety improvement experiences and discuss the way forward by indicating opportunities and countermeasures that could be implemented to achieve a new level of safety in Asia. METHODS: This study provides a review and analyses of data in the literature, including from the World Health Organization (WHO) and World Bank, and a review of lessons learned from best practices in high-income countries. In addition, an estimation of costs due to road transport injuries in Asia and review of future trends in road transport is provided. RESULTS: Data on the global and Asian road safety problem and status of prevention strategies in Asia as well as recommendations for future actions are discussed. The total number of deaths due to road accidents in the 24 Asian countries, encompassing 56% of the total world population, is 750,000 per year (statistics 2010). The total number of injuries is more than 50 million, of which 12% are hospital admissions. The loss to the economy in the 24 Asian countries is estimated to around US$800 billion or 3.6% of the gross domestic product (GDP). CONCLUSIONS: This article clearly shows that road safety is causing large problems and high costs in Asia, with an enormous impact on the well-being of people, economy, and productivity. In many Asian low- and middle-income countries, the yearly number of fatalities and injuries is increasing. Vulnerable road users (pedestrians, cyclists, and motorcyclists combined) are particularly at risk. Road safety in Asia should be given rightful attention, including taking powerful, effective actions. This review stresses the need for reliable accident data, because there is considerable underreporting in the official statistics. Reliable accident data are imperative to determine evidence-based intervention strategies and monitor the success of these interventions and analyses. On the other hand, lack of good high-quality accident data should not be an excuse to postpone interventions. There are many opportunities for evidence-based transport safety improvements, including measures concerning the 5 key risk factors: speed, drunk driving, not wearing motorcycle helmets, not wearing seat belts, and not using child restraints in cars, as specified in the Decade of Action for Road Safety 2011 2020. In this commentary, a number of additional measures are proposed that are not covered in the Decade of Action Plan. These new measures include separate roads or lanes for pedestrians and cyclists; helmet wearing for e-bike riders; special attention to elderly persons in public transportation; introduction of emerging collision avoidance technologies, in particular automatic emergency braking (AEB) and alcohol locks; improved truck safety focusing on the other road user (including blind spot detection technology; underride protection at the front, rear, and side; and energy-absorbing fronts); and improvements in motorcycle safety concerning protective clothing, requirements for advanced braking systems, improved visibility of motorcycles by using daytime running lights, and better guardrails. PMID- 26148216 TI - Low-voltage operation of ZrO2-gated n-type thin-film transistors based on a channel formed by hybrid phases of SnO and SnO2. AB - With SnO typically regarded as a p-type oxide semiconductor, an oxide semiconductor formed by hybrid phases of mainly SnO and a small amount of SnO2 with an average [O]/[Sn] ratio of 1.1 was investigated as a channel material for n-type thin-film transistors (TFTs). Furthermore, an appropriate number of oxygen vacancies were introduced into the oxide during annealing at 400 degrees C in ambient N2, making both SnO and SnO2 favorable for current conduction. By using high-kappa ZrO2 with a capacitance equivalent thickness of 13.5 nm as the gate dielectric, the TFTs processed at 400 degrees C demonstrated a steep subthreshold swing (SS) of 0.21 V/dec, and this can be ascribed to the large gate capacitance along with a low interface trap density (Dit) value of 5.16 * 10(11) cm(-2) eV(-1). In addition, the TFTs exhibit a relatively high electron mobility of 7.84 cm(2)/V.s, high ON/OFF current ratios of up to 2.5 * 10(5), and a low gate leakage current at a low operation voltage of 3 V. The TFTs also prove its high reliability performance by showing negligible degradation of SS and threshold voltage (VT) against high field stress (-10 MV/cm). When 3% oxygen annealing is combined with a thinner channel thickness, TFTs with even higher ION/IOFF ratios exceeding 10(7) can also be obtained. With these promising characteristics, the overall performance of the TFTs displays competitive advantages compared with other n-type TFTs formed on binary or even some multicomponent oxide semiconductors and paves a promising and economic avenue to implement an n-type oxide semiconductor without doping for production-worthy TFT technology. Most importantly, when combined with the typical SnO-based p-type oxide semiconductor, it would usher in a new era in achieving high-performance complementary metal oxide semiconductor circuits by using the same SnO-based oxide semiconductor. PMID- 26148215 TI - Structure and gating of CLC channels and exchangers. AB - Since their serendipitous discovery the CLC family of Cl(-) transporting proteins has been a never ending source of surprises. From their double-barrelled architecture to their complex structure and divergence as channels and transporters, the CLCs never cease to amaze biophysicists, biochemists and physiologists alike. These unusual functional properties allow the CLCs to fill diverse physiological niches, regulating processes that range from muscle contraction to acidification of intracellular organelles, nutrient accumulation and survival of bacteria to environmental stresses. Over the last 15 years, the availability of atomic-level information on the structure of the CLCs, coupled to the discovery that the family is divided into passive channels and secondary active transporters, has revolutionized our understanding of their function. These breakthroughs led to the identification of the key structural elements regulating gating, transport, selectivity and regulation by ligands. Unexpectedly, many lines of evidence indicate that the CLC exchangers function according to a non-conventional transport mechanism that defies the fundamental tenets of the alternating-access paradigm for exchange transport, paving the way for future unexpected insights into the principles underlying active transport and channel gating. PMID- 26148217 TI - Acute Myocardial Infarction Complicated by Cardiogenic Shock: An Algorithm-Based Extracorporeal Membrane Oxygenation Program Can Improve Clinical Outcomes. AB - Extracorporeal membrane oxygenation (ECMO) in our institution resulted in near total mortality prior to the establishment of an algorithm-based program in July 2010. We hypothesized that an algorithm-based ECMO program improves the outcome of patients with acute myocardial infarction complicated with cardiogenic shock. Between March 2003 and July 2013, 29 patients underwent emergent catheterization for acute myocardial infarction due to left main or proximal left anterior descending artery occlusion complicated with cardiogenic shock (defined as systolic blood pressure <90 mm Hg despite multiple inotropes, with or without intra-aortic balloon pump, lactic acidosis). Of 29 patients, 15 patients were treated before July 2010 (Group 1, old program), and 14 patients were treated after July 2010 (Group 2, new program). There were no significant differences in the baseline characteristics, including age, sex, coronary risk factors, and left ventricular ejection fraction between the two groups. Cardiopulmonary resuscitation prior to ECMO was performed in two cases (13%) in Group 1 and four cases (29%) in Group 2. ECMO support was performed in one case (6.7%) in Group 1 and six cases (43%) in Group 2. The 30-day survival of Group 1 versus Group 2 was 40 versus 79% (P = 0.03), and 1-year survival rate was 20 versus 56% (P = 0.01). The survival rate for patients who underwent ECMO was 0% in Group 1 versus 83% in Group 2 (P = 0.09). In Group 2, the mean duration on ECMO was 9.8 +/- 5.9 days. Of the six patients who required ECMO in Group 2, 100% were successfully weaned off ECMO or were bridged to ventricular assist device implantation. Initiation of an algorithm-based ECMO program improved the outcomes in patients with acute myocardial infarction complicated by cardiogenic shock. PMID- 26148218 TI - Evolutionary and structural analyses of heterodimeric proteins composed of subunits with same fold. AB - Heterodimeric proteins with homologous subunits of same fold are involved in various biological processes. The objective of this study is to understand the evolution of structural and functional features of such heterodimers. Using a non redundant dataset of 70 such heterodimers of known 3D structure and an independent dataset of 173 heterodimers from yeast, we note that the mean sequence identity between interacting homologous subunits is only 23-24% suggesting that, generally, highly diverged paralogues assemble to form such a heterodimer. We also note that the functional roles of interacting subunits/domains are generally quite different. This suggests that, though the interacting subunits/domains are homologous, the high evolutionary divergence characterize their high functional divergence which contributes to a gross function for the heterodimer considered as a whole. The inverse relationship between sequence identity and RMSD of interacting homologues in heterodimers is not followed. We also addressed the question of formation of homodimers of the subunits of heterodimers by generating models of fictitious homodimers on the basis of the 3D structures of the heterodimers. Interaction energies associated with these homodimers suggests that, in overwhelming majority of the cases, such homodimers are unlikely to be stable. Majority of the homologues of heterodimers of known structures form heterodimers (51.8%) and a small proportion (14.6%) form homodimers. Comparison of 3D structures of heterodimers with homologous homodimers suggests that interfacial nature of residues is not well conserved. In over 90% of the cases we note that the interacting subunits of heterodimers are co-localized in the cell. PMID- 26148219 TI - Diet and exercise improve chemoreflex sensitivity in patients with metabolic syndrome and obstructive sleep apnea. AB - OBJECTIVE: Chemoreflex hypersensitity was caused by obstructive sleep apnea (OSA) in patients with metabolic syndrome (MetS). This study tested the hypothesis that hypocaloric diet and exercise training (D+ET) would improve peripheral and central chemoreflex sensitivity in patients with MetS and OSA. METHODS: Patients were assigned to: (1) D+ET (n = 16) and (2) no intervention control (C, n = 8). Minute ventilation (VE, pre-calibrated pneumotachograph) and muscle sympathetic nerve activity (MSNA, microneurography) were evaluated during peripheral chemoreflex sensitivity by inhalation of 10% O2 and 90% N2 with CO2 titrated and central chemoreflex by 7% CO2 and 93% O2 for 3 min at study entry and after 4 months. RESULTS: Peak VO2 was increased by D+ET; body weight, waist circumference, glucose levels, systolic/diastolic blood pressure, and apnea hypopnea index (AHI) (34 +/- 5.1 vs. 18 +/- 3.2 events/h, P = 0.04) were reduced by D+ET. MSNA was reduced by D+ET at rest and in response to hypoxia (8.6 +/- 1.2 vs. 5.4 +/- 0.6 bursts/min, P = 0.02), and VE in response to hypercapnia (14.8 +/ 3.9 vs. 9.1 +/- 1.2 l/min, P = 0.02). No changes were found in the C group. A positive correlation was found between AHI and MSNA absolute changes (R = 0.51, P = 0.01) and body weight and AHI absolute changes (R = 0.69, P < 0.001). CONCLUSIONS: Sympathetic peripheral and ventilatory central chemoreflex sensitivity was improved by D+ET in MetS+OSA patients, which may be associated with improvement in sleep pattern. PMID- 26148221 TI - Classification of Sunflower Oil Blends Stabilized by Oleoresin Rosemary (Rosmarinus officinalis L.) Using Multivariate Kinetic Approach. AB - The sunflower oil-oleoresin rosemary (Rosmarinus officinalis L.) blends (SORB) at 9 different concentrations (200 to 2000 mg/kg), sunflower oil-tertiary butyl hydroquinone (SOTBHQ ) at 200 mg/kg and control (without preservatives) (SO control ) were oxidized using Rancimat (temperature: 100 to 130 degrees C; airflow rate: 20 L/h). The oxidative stability of blends was expressed using induction period (IP), oil stability index and photochemiluminescence assay. The linear regression models were generated by plotting ln IP with temperature to estimate the shelf life at 20 degrees C (SL20 ; R(2) > 0.90). Principal component analysis (PCA) and hierarchical cluster analysis (HCA) was used to classify the oil blends depending upon the oxidative stability and kinetic parameters. The Arrhenius equation adequately described the temperature-dependent kinetics (R(2) > 0.90, P < 0.05) and kinetic parameters viz. activation energies, activation enthalpies, and entropies were calculated in the range of 92.07 to 100.50 kJ/mol, 88.85 to 97.28 kJ/mol, -33.33 to -1.13 J/mol K, respectively. Using PCA, a satisfactory discrimination was noted among SORB, SOTBHQ , and SOcontrol samples. HCA classified the oil blends into 3 different clusters (I, II, and III) where SORB1200 and SORB1500 were grouped together in close proximity with SOTBHQ indicating the comparable oxidative stability. The SL20 was estimated to be 3790, 6974, and 4179 h for SO control, SOTBHQ, and SORB1500, respectively. The multivariate kinetic approach effectively screened SORB1500 as the best blend conferring the highest oxidative stability to sunflower oil. This approach can be adopted for quick and reliable estimation of the oxidative stability of oil samples. PMID- 26148222 TI - Cytomegalovirus and other common enteric viruses are not commonly associated with NEC. AB - AIM: Changes in gut microbiota may contribute to NEC, but most studies focus on bacteria. Case reports suggest a link between cytomegalovirus (CMV) or other enteric viruses and NEC, but there are few case series systematically looking at common potential viral causes. We aimed to assess the presence of candidate viruses in blood or stool of a case series of infants with NEC managed in one surgical centre. METHODS: We identified 22 infants diagnosed with NEC (from November 2011 to March 2014): 17 had suitable blood stored, of whom 14 also had suitable stool samples stored. Blood was analysed with polymerase chain reaction (PCR) for CMV, Epstein-Barr virus (EBV) and adenovirus, and stool by PCR for norovirus, sappovirus, astrovirus, adenovirus and rotavirus. RESULTS: All samples were negative. CONCLUSION: Although case reports indicate an episodic association of enteric viruses in NEC, the inability to detect any of these viruses in our 17 NEC infants suggests that a viral aetiology is unlikely to be causative for most sporadic forms of NEC. PMID- 26148223 TI - European Stroke Organisation (ESO) guidelines for the management of temperature in patients with acute ischemic stroke. AB - BACKGROUND: Hyperthermia is a frequent complication in patients with acute ischemic stroke. On the other hand, therapeutically induced hypothermia has shown promising potential in animal models of focal cerebral ischemia. This Guideline Document presents the European Stroke Organisation guidelines for the management of temperature in patients with acute ischemic stroke. METHODS: A multidisciplinary group identified related questions and developed its recommendations based on evidence from randomized controlled trials elaborating the Grading of Recommendations Assessment, Development, and Evaluation approach. This Guideline Document was reviewed within the European Stroke Organisation and externally and was approved by the European Stroke Organisation Guidelines Committee and the European Stroke Organisation Executive Committee. RESULTS: We found low-quality evidence, and therefore, we cannot make any recommendation for treating hyperthermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and hyperthermia; moderate evidence to suggest against routine prevention of hyperthermia with antipyretics as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and normothermia; very low-quality evidence to suggest against routine induction of hypothermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke. CONCLUSIONS: The currently available data about the management of temperature in patients with acute ischemic stroke are limited, and the strengths of the recommendations are therefore weak. We call for new randomized controlled trials as well as recruitment of eligible patients to ongoing randomized controlled trials to allow for better-informed recommendations in the future. PMID- 26148224 TI - Elastic Vibrations in the Photosynthetic Bacterial Reaction Center Coupled to the Primary Charge Separation: Implications from Molecular Dynamics Simulations and Stochastic Langevin Approach. AB - Primary electron transfer reactions in the bacterial reaction center are difficult for theoretical explication: the reaction kinetics, almost unalterable over a wide range of temperature and free energy changes, revealed oscillatory features observed initially by Shuvalov and coauthors (1997, 2002). Here the reaction mechanism was studied by molecular dynamics and analyzed within a phenomenological Langevin approach. The spectral function of polarization around the bacteriochlorophyll special pair PLPM and the dielectric response upon the formation of PL(+)PM(-) dipole within the special pair were calculated. The system response was approximated by Langevin oscillators; the respective frequencies, friction, and energy coupling coefficients were determined. The protein dynamics around PL and PM were distinctly asymmetric. The polarization around PL included slow modes with the frequency 30-80 cm(-1) and the total amplitude of 130 mV. Two main low-frequency modes of protein response around PM had frequencies of 95 and 155 cm(-1) and the total amplitude of 30 mV. In addition, a slowly damping mode with the frequency of 118 cm(-1) and the damping time >1.1 ps was coupled to the formation of PL(+)PM(-) dipole. It was attributed to elastic vibrations of alpha-helices in the vicinity of PLPM. The proposed trapping of P excitation energy in the form of the elastic vibrations can rationalize the observed properties of the primary electron transfer reactions, namely, the unusual temperature and DeltaG dependences, the oscillating phenomena in kinetics, and the asymmetry of the charge separation reactions. PMID- 26148225 TI - I148M variant in PNPLA3 reduces central adiposity and metabolic disease risks while increasing nonalcoholic fatty liver disease. AB - BACKGROUND & AIMS: The I148M variant because of the substitution of C to G in PNPLA3 (rs738409) is associated with the increased risk of nonalcoholic fatty liver disease (NAFLD). In liver, I148M variant reduces hydrolytic function of PNPLA3, which results in hepatic steatosis; however, its association with the other clinical phenotype such as adiposity and metabolic diseases is not well established. METHODS: To identify the impact of I148M variant on clinical risk factors of NAFLD, we recruited 1363 generally healthy Korean males after excluding alcoholic and secondary causes of hepatic steatosis. Central adiposity was assessed by computed tomography, and hepatic steatosis was evaluated by abdominal ultrasonography. RESULTS: The participants were predominantly middle aged (49.0 +/- 7.1 years; range 30-60 years), and the frequency of NAFLD was 44.2%. The rs738409-G allele carriers had a 1.19-fold increased risk for NAFLD (minor allele frequency 0.43; allelic odds ratio 1.38; P = 4.3 * 10(-5) ). Interestingly, the rs738409 GG carriers showed significantly lower levels of visceral and subcutaneous adiposity (P < 0.001 and = 0.015, respectively), BMI (P < 0.001), triglycerides (P < 0.001) and insulin resistance (P = 0.002) compared to CC carriers. These negative associations between clinical risk factors and rs738409-G dosage were more prominent in non-NAFLD group compared to those in NAFLD group. CONCLUSIONS: The I148M variant, although increasing the risk of NAFLD, was associated with reduced levels of central adiposity, BMI, serum triglycerides and insulin resistance, suggesting differential roles in fat storage and distribution according to cell types and metabolic status. PMID- 26148226 TI - Ethanol Promotes Cell Migration via Activation of Chloride Channels in Nasopharyngeal Carcinoma Cells. AB - BACKGROUND: Excessive alcohol consumption has been identified as a significant risk factor for cancer development. Chloride channels have been proved previously by us and others to be involved in cancer cell migration. However, it is unknown whether chloride channels are associated with the effects of ethanol (EtOH) on cancer cell activities. METHODS: The effects of EtOH on migration were detected by the wound healing assay in the nasopharyngeal carcinoma cells (CNE-2Z) and the normal nasopharyngeal epithelial cells (NP69-SV40T). The whole-cell patch clamp technique was used to record the EtOH-induced chloride current. The characteristics of the current were studied by anion substitution, hypertonic challenges, and channel blockers. RESULTS: EtOH promoted the migration of cancerous CNE-2Z cells, but could hardly affect the migration of normal NP69 SV40T cells. The EtOH-induced migration could be inhibited by the chloride channel blockers, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and tamoxifen. The exposure of CNE-2Z cells to EtOH activated a chloride current, with the ion selectivity of I(-) >Br(-) > Cl(-) >gluconate, demonstrated by ion substitution experiments. EtOH could still activate a similar chloride current in the absence of Ca(2+) in the medium. The current could be inhibited by the hypertonicity-induced cell shrinkage and the channel blockers NPPB and tamoxifen. EtOH could also activate a chloride current in normal NP69-SV40T cells, with the properties similar to those in CNE-2Z cells, but the current density was much smaller than that recorded in cancerous CNE-2Z cells. CONCLUSIONS: It has been demonstrated in this study that EtOH can activate chloride channels and promote cell migration in cancerous cells, but can hardly affect the activities in normal cells. The data suggest for the first time that EtOH may promote cell migration via activation of chloride channels; long-term exposure to EtOH may increase the incident of tumor metastasis. PMID- 26148227 TI - Characteristics of Reconstituted Tight Junctions After Corneal Epithelial Wounds and Ultrastructure Alterations of Corneas in Type 2 Diabetic Rats. AB - PURPOSE: To investigate the characteristics of reconstituted tight junctions after corneal epithelial wounds and ultrastructure alterations of corneas in a high-fat diet combined with streptozocin (STZ)-induced rat model of type 2 diabetes mellitus (DM). MATERIALS AND METHODS: One-hundred Sprague-Dawley male rats were randomly divided into diabetic and normal control groups (n = 50 each). A high-fat diet combined with intraperitoneal STZ injection was used to induce type 2 DM. Wound healing was determined using an in vivo corneal epithelial debridement model. Scanning electron microscopy (SEM) was used to study differences in corneal epithelium between diabetic and normal rats. The rate of corneal wound healing was observed by fluorescein and hematoxylin and eosin staining. Diabetic and healthy rats were sacrificed before debridement and 16, 48, 72, and 120 hours afterwards for Western blot and immunofluorescence. RESULTS: Corneal epithelial cell connection abnormalities, dropsy, and microvillus reduction were evident by SEM. Corneal epithelial wound closure rates were decreased in diabetic rats compared with normal rats. Immunofluorescence and Western blot analysis demonstrated that occludin expression in the corneal epithelium of the diabetic group was weaker compared to the normal group at the 16 and 48 hour time-points after debridement. CONCLUSIONS: Abnormal occludin expression may contribute to delayed epithelial wound healing in diabetic corneas. PMID- 26148228 TI - Effects of pupil dilation on objective refraction. PMID- 26148229 TI - Integrin alpha11beta1 regulates cancer stromal stiffness and promotes tumorigenicity and metastasis in non-small cell lung cancer. AB - Integrin alpha11beta1 is a stromal cell-specific receptor for fibrillar collagens and is overexpressed in carcinoma-associated fibroblasts (CAFs). We have investigated its direct role in cancer progression by generating severe combined immune deficient (SCID) mice deficient in integrin alpha11 (alpha11) expression. The growth of A549 lung adenocarcinoma cells and two patient-derived non-small cell lung carcinoma (NSCLC) xenografts in these alpha11 knockout (alpha11(-/-)) mice was significantly impeded, as compared with wild-type (alpha11(+/+)) SCID mice. Orthotopic implantation of a spontaneously metastatic NCI-H460SM cell line into the lungs of alpha11(-/-) and alpha11(+/+) mice showed significant reduction in the metastatic potential of these cells in the alpha11(-/-) mice. We identified that collagen cross-linking is associated with stromal alpha11 expression, and the loss of tumor stromal alpha11 expression was correlated with decreased collagen reorganization and stiffness. This study shows the role of integrin alpha11beta1, a receptor for fibrillar collagen in differentiation of fibroblasts into CAFs. Furthermore, our data support an important role for alpha11 signaling pathway in CAFs, promoting tumor growth and metastatic potential of NSCLC cells and being closely associated with collagen cross-linking and the organization and stiffness of fibrillar collagen matrices. PMID- 26148220 TI - MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation. AB - Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards. PMID- 26148230 TI - The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia. AB - The ETS transcription factor ERG has been implicated as a major regulator of both normal and aberrant hematopoiesis. In acute myeloid leukemias harboring t(16;21), ERG function is deregulated due to a fusion with FUS/TLS resulting in the expression of a FUS-ERG oncofusion protein. How this oncofusion protein deregulates the normal ERG transcription program is unclear. Here, we show that FUS-ERG acts in the context of a heptad of proteins (ERG, FLI1, GATA2, LYL1, LMO2, RUNX1 and TAL1) central to proper expression of genes involved in maintaining a stem cell hematopoietic phenotype. Moreover, in t(16;21) FUS-ERG co occupies genomic regions bound by the nuclear receptor heterodimer RXR:RARA inhibiting target gene expression and interfering with hematopoietic differentiation. All-trans retinoic acid treatment of t(16;21) cells as well as FUS-ERG knockdown alleviate the myeloid-differentiation block. Together, the results suggest that FUS-ERG acts as a transcriptional repressor of the retinoic acid signaling pathway. PMID- 26148231 TI - p54(nrb)/NONO regulates lipid metabolism and breast cancer growth through SREBP 1A. AB - Dysregulation of lipid metabolism is common in breast cancer. However, the underlying mechanisms remain elusive and the contribution of aberrant lipid metabolism to the malignant phenotypes of breast cancer is poorly understood. Here, we show that the nuclear protein p54(nrb)/Nono is highly expressed in breast cancer tissues as compared with the adjacent normal tissues in human patients. To determine the functions of p54(nrb) in breast cancer, we performed a biochemical screen and identified SREBP-1a, a master activator for genes involved in lipid biosynthesis, as a novel interacting protein of p54(nrb). In human breast cancer tissues, the levels of p54(nrb) and SREBP-1a proteins were positively correlated with each other. Our biochemical analyses showed that the conserved Y267 residue of p54(nrb) was required for its binding to the nuclear form of SREBP-1a. Interestingly, p54(nrb) binding to nuclear SREBP-1a caused an increase of nuclear SREBP-1a protein stability. As a result, p54(nrb) stimulates SREBP-1-meidated transcription of lipogenic genes and lipid production in breast cancer cells. Moreover, both p54(nrb) and SREBP-1a were required for breast cancer cell growth in vitro, and p54(nrb) binding to nuclear SREBP-1a was also critical for breast tumor development in vivo. Together, we conclude that p54(nrb) is a novel regulator of SREBP-1a in the nucleus, and our data suggest that p54(nrb) regulation of SREBP-1a supports the increased cellular demand of lipids for breast cancer growth. Thus, the SREBP pathway may represent a novel target for treating breast cancer. PMID- 26148232 TI - Decreased LRIG1 in fulvestrant-treated luminal breast cancer cells permits ErbB3 upregulation and increased growth. AB - ErbB3, a member of the ErbB family of receptor tyrosine kinases, is a potent activator of phosphatidyl inositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling, driving tumor cell survival and therapeutic resistance in breast cancers. In luminal breast cancers, ErbB3 upregulation following treatment with the antiestrogen fulvestrant enhances PI3K/mTOR-mediated cell survival. However, the mechanism by which ErbB3 is upregulated in fulvestrant-treated cells is unknown. We found that ErbB3 protein levels and cell surface presentation were increased following fulvestrant treatment, focusing our attention on proteins that regulate ErbB3 at the cell surface, including Nrdp1, NEDD4 and LRIG1. Among these, only LRIG1 correlated positively with ERalpha, but inversely with ErbB3 in clinical breast cancer data sets. LRIG1, an estrogen inducible ErbB downregulator, was decreased in a panel of fulvestrant-treated luminal breast cancer cells. Ectopic LRIG1 expression from an estrogen independent promoter uncoupled LRIG1 from estrogen regulation, thus sustaining LRIG1 and maintaining low ErbB3 levels in fulvestrant-treated cells. An LRIG1 mutant lacking the ErbB3 interaction motif was insufficient to downregulate ErbB3. Importantly, LRIG1 overexpression improved fulvestrant-mediated growth inhibition, whereas cells expressing the LRIG1 mutant were poorly sensitive to fulvestrant, despite effective ERalpha downregulation. Consistent with these results, LRIG1 expression correlated positively with increased disease-free survival in antiestrogen-treated breast cancer patients. These data suggest that ERalpha-dependent expression of LRIG1 dampens ErbB3 signaling in luminal breast cancer cells, and by blocking ERalpha activity with fulvestrant, LRIG1 is decreased thus permitting ErbB3 accumulation, enhanced ErbB3 signaling to cell survival pathways and blunting therapeutic response to fulvestrant. PMID- 26148233 TI - Regulation of complement-dependent cytotoxicity by TGF-beta-induced epithelial mesenchymal transition. AB - The process of epithelial-mesenchymal transition (EMT), in addition to being an initiating event for tumor metastasis, is implicated in conferring several clinically relevant properties to disseminating cancer cells. These include stem cell-like properties, resistance to targeted therapies and ability to evade immune surveillance. Enrichment analysis of gene expression changes during transforming growth factor-beta (TGF-beta)-induced EMT in lung cancer cells identified complement cascade as one of the significantly enriched pathway. Further analysis of the genes in the complement pathway revealed an increase in the expression of complement inhibitors and a decrease in the expression of proteins essential for complement activity. In this study, we tested whether EMT confers resistance to complement-dependent cytotoxicity (CDC) in lung cancer cells and promotes tumor progression. CD59 is a potent inhibitor of membrane attack complex that mediates complement-dependent cell lysis. We observed a significant increase in the CD59 expression on the surface of cells after TGF beta-induced EMT. Furthermore, CD59 knockdown restored susceptibility of cells undergoing EMT to cetuximab-mediated CDC. TGF-beta-induced CD59 expression during EMT is dependent on Smad3 but not on Smad2. Chromatin immunoprecipitation analysis confirmed that Smad3 directly binds to the CD59 promoter. Stable knockdown of CD59 in A549 cells inhibited experimental metastasis. These results demonstrate that TGF-beta-induced EMT and CD59 expression confers an immune evasive mechanism to disseminating tumor cells facilitating tumor progression. Together, our data demonstrates that CD59 inhibition may serve as an adjuvant to enhance the efficacy of antibody-mediated therapies, as well as to inhibit metastasis in lung cancer. PMID- 26148234 TI - BIRC5/Survivin as a target for glycolysis inhibition in high-stage neuroblastoma. AB - Adverse forms of neuroblastoma (NB), a childhood malignancy that develops from immature neuronal progenitor cells frequently carry a gain of chromosome 17q, which leads to overexpression of the antiapoptotic protein BIRC5/Survivin. We have recently shown that high Survivin expression shuts down mitochondrial complex I activity and shifts NB cells from oxidative phosphorylation to aerobic glycolysis, which further increases resistance to cell death induction. This increased glucose consumption sensitized tumor cells to glycolysis inhibitors. Interestingly, in Survivin-overexpressing cells 2-deoxy-d-glucose (2DG) treatment induces re-fusion of mitochondrial networks after 4 h, which coincides with Survivin repression. 2DG selectively acts on Survivin-expressing NB cells and induces autophagic degradation of Survivin via activation of the E3-ubiquitin ligase Parkin, a downstream target of PINK1. Survivin degradation further releases bound Beclin-1, which enhances autophagy and cell death induction. Knockdown of Parkin, however, reduces the sensitivity of Survivin-expressing NB cells to glycolysis inhibition. The selective activity of 2DG treatment on Survivin-overexpressing tumor cells was also confirmed in a xenograft mouse model, which further supports our hypothesis that glycolysis inhibitors might be useful drugs in the treatment of NB. PMID- 26148235 TI - RING finger protein 31 promotes p53 degradation in breast cancer cells. AB - The atypical E3 ubiquitin ligase RNF31 is highly expressed in human breast cancer, the most frequent neoplastic lethality among women. Here, RNF31 depletion in breast cancer cells in combination with global gene expression profiling revealed p53 (TP53) signaling as a potential RNF31 target. Interestingly, RNF31 decreased p53 stability, whereas depletion of RNF31 in breast cancer cells caused cell cycle arrest and cisplatin-induced apoptosis in a p53-dependent manner. Furthermore, RNF31 associated with the p53/MDM2 complex and facilitated p53 polyubiquitination and degradation by stabilizing MDM2, suggesting a molecular mechanism by which RNF31 regulates cell death. Analysis of publically available clinical data sets displayed a negative correlation between RNF31 and p53 target genes, including IGFBP3 and BTG1, consistent with RNF31 regulating p53 function in vivo as well. Together, our findings suggest RNF31 as a potential therapeutic target to restore p53 function in breast cancer. PMID- 26148236 TI - Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming. AB - Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of the electron transport chain component cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage-dependent growth and acquired invasive phenotypes. Disruption of the CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling includes activation of PI3-kinase, IGF1R and Akt, Ca2(+)-sensitive transcription factors and also TGFbeta1, MMP16 and periostin, which are involved in oncogenic progression. Whole-genome expression analysis showed the upregulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mitochondrial DNA depletion, although distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be the hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in the CcO complex can potentially induce tumor progression. PMID- 26148237 TI - Structural basis of how stress-induced MDMX phosphorylation activates p53. AB - The tumor-suppressor protein p53 is tightly controlled in normal cells by its two negative regulators--the E3 ubiquitin ligase MDM2 and its homolog MDMX. Under stressed conditions such as DNA damage, p53 escapes MDM2- and MDMX-mediated functional inhibition and degradation, acting to prevent damaged cells from proliferating through induction of cell cycle arrest, DNA repair, senescence or apoptosis. Ample evidence suggests that stress signals induce phosphorylation of MDM2 and MDMX, leading to p53 activation. However, the structural basis of stress induced p53 activation remains poorly understood because of the paucity of technical means to produce site-specifically phosphorylated MDM2 and MDMX proteins for biochemical and biophysical studies. Herein, we report total chemical synthesis, via native chemical ligation, and functional characterization of (24-108)MDMX and its Tyr99-phosphorylated analog with respect to their ability to interact with a panel of p53-derived peptide ligands and PMI, a p53-mimicking but more potent peptide antagonist of MDMX, using FP and surface plasmon resonance techniques. Phosphorylation of MDMX at Tyr99 weakens peptide binding by approximately two orders of magnitude. Comparative X-ray crystallographic analyses of MDMX and of pTyr99 MDMX in complex with PMI as well as modeling studies reveal that the phosphate group of pTyr99 imposes extensive steric clashes with the C-terminus of PMI or p53 peptide and induces a significant lateral shift of the peptide ligand, contributing to the dramatic decrease in the binding affinity of MDMX for p53. Because DNA damage activates c-Abl tyrosine kinase that phosphorylates MDMX at Tyr99, our findings afford a rare glimpse at the structural level of how stress-induced MDMX phosphorylation dislodges p53 from the inhibitory complex and activates it in response to DNA damage. PMID- 26148239 TI - From zero to sixty: cell death signaling in the city that never sleeps. PMID- 26148238 TI - RhoB loss induces Rac1-dependent mesenchymal cell invasion in lung cells through PP2A inhibition. AB - Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, which is mainly due to its high risk of metastatic dissemination. One critical point of this process is the ability of cancer cells to detach from the primary tumor and migrate through the extracellular matrix; however, the underlying molecular mechanisms are not yet fully understood. In the present study, we identified the small GTPase RhoB as a key regulator of bronchial cell morphology in a three-dimensional (3D) matrix. RhoB loss, which is frequently observed during lung cancer progression, induced an epithelial-mesenchymal transition (EMT) characterized by an increased proportion of invasive elongated cells in 3D. The process was mediated by Slug induction and E-cadherin repression. In addition, downregulation of RhoB induced Akt1 activation, which in turn activated Rac1 through the guanine-exchange factor Trio to control cell shape rearrangement. Further, we provide evidence that RhoB interacted with and positively regulates phosphatase PP2A through the recruitment of its regulatory subunit B55, which was found to be crucial for Akt dephosphorylation. B55 inhibition completely suppressed RhoB-mediated PP2A regulation. Finally, we show that PP2A inactivation, by targeting either its catalytic or its regulatory B55 subunit, completely reversed RhoB-dependent morphological changes and also fully prevented the ability of RhoB to decrease the invasiveness of bronchial cells. Altogether, these results highlight a novel signaling axis and describe new molecular mechanisms that could explain the tumor suppressor role of RhoB in lung cancer. Therefore, we propose that RhoB could be responsible for early metastatic prevention by inhibiting the EMT-derived invasiveness of lung cells through the control of PP2A activity. PMID- 26148241 TI - Known structure, unknown function: An inquiry-based undergraduate biochemistry laboratory course. AB - Undergraduate biochemistry laboratory courses often do not provide students with an authentic research experience, particularly when the express purpose of the laboratory is purely instructional. However, an instructional laboratory course that is inquiry- and research-based could simultaneously impart scientific knowledge and foster a student's research expertise and confidence. We have developed a year-long undergraduate biochemistry laboratory curriculum wherein students determine, via experiment and computation, the function of a protein of known three-dimensional structure. The first half of the course is inquiry-based and modular in design; students learn general biochemical techniques while gaining preparation for research experiments in the second semester. Having learned standard biochemical methods in the first semester, students independently pursue their own (original) research projects in the second semester. This new curriculum has yielded an improvement in student performance and confidence as assessed by various metrics. To disseminate teaching resources to students and instructors alike, a freely accessible Biochemistry Laboratory Education resource is available at http://biochemlab.org. PMID- 26148240 TI - OTUB1 inhibits the ubiquitination and degradation of FOXM1 in breast cancer and epirubicin resistance. AB - The forkhead transcription factor FOXM1 has a key role in DNA damage response, and its deregulated overexpression is associated with genotoxic drug resistance in breast cancer. However, little is known about the posttranslational mechanisms by which FOXM1 expression is regulated by genotoxic agents and how they are deregulated in resistant cells. Initial co-immunoprecipitation studies verified previous proteomic analysis finding that the OTUB1 is a novel FOXM1-interacting protein. Western blot analysis showed that both OTUB1 and FOXM1 expression reduced upon genotoxic agent treatment in MCF-7 cells, but remained relatively constant in resistant cells. FOXM1 expression reduced upon OTUB1 depletion by siRNA and increased with OTUB1 overexpression in MCF-7 cells, arguing that OTUB1 positively regulates FOXM1 expression. In agreement, co-immunoprecipitation experiments demonstrated that FOXM1 expression is associated with OTUB1 binding but inversely correlates with conjugation to the protein degradation-associated Lys-48-linked ubiquitin-chains. Overexpression of wild-type (WT) OTUB1, but not the OTUB1(C91S) mutant, disrupted the formation of Lys48-linked ubiquitin conjugates on FOXM1. Importantly, knockdown of OTUB1 by siRNA resulted in an increase in turnover of FOXM1 in MCF-7 cells treated with the protein synthesis inhibitor cycloheximide, whereas overexpression of WT OTUB1, but not the OTUB1(C91S) mutant, significantly enhances the half-life of FOXM1. In addition, proliferative and clonogenic assays also show that OTUB1 can enhance the proliferative rate and epirubicin resistance through targeting FOXM1, as OTUB1 has little effect on FOXM1-deficient cells. The physiological relevance of the regulation of FOXM1 by OTUB1 is further underscored by the significant correlations between FOXM1 and OTUB1 expression in breast cancer patient samples. Cox-regression survival analysis indicates that OTUB1 overexpression is linked to poorer outcome in particular in patients treated with chemotherapy. Collectively, these data suggest that OTUB1 limits the ubiquitination and degradation of FOXM1 in breast cancer and has a key role in genotoxic agent resistance. PMID- 26148242 TI - Low-energy density and high fiber intake are dietary concerns in female endurance athletes. AB - Low or reduced energy availability (LEA) is linked to functional hypothalamic oligomenorrhea/amenorrhea (FHA), which is frequently reported in weight-sensitive sports. This makes LEA a major nutritional concern for female athletes. The aim of this study was to describe dietary characteristics of athletes with LEA and/or FHA. Endurance athletes (n = 45) were recruited from national teams and competitive clubs. Protocols included gynecological examination, body composition, eating disorder evaluation, and 7-day dietary intake and EA assessment. Athletes with disordered eating behavior/eating disorders (n = 11), menstrual dysfunction other than FHA (n = 5), and low dietary record validity (n = 4) were excluded. Remaining subjects (n = 25) were characterized by EA [optimal: >= 45 kcal (188 kJ)/kg fat-free mass (FFM)/day (n = 11), LEA: < 45 kcal (188 kJ)/kg FFM/day (n = 14)] and reproductive function [eumenorrhea (EUM; n = 10), FHA (n = 15)]. There was no difference in EA between FHA and EUM subjects. However, FHA and LEA subjects shared the same dietary characteristics of lower energy density (ED) [(P = 0.012; P = 0.020), respectively], and fat content [(P = 0.047; P = 0.027), respectively]. Furthermore, FHA subjects had a lower intake of carbohydrate-rich foods (P = 0.019), higher fiber content (P < 0.001), and drive for thinness score (P = 0.003). Conclusively, low ED together with high fiber content may constitute targets for dietary intervention in order to prevent and treat LEA and FHA in female athletes. PMID- 26148243 TI - Thin yellow papules and plaques on the eyelids, cheeks, and neck. PMID- 26148244 TI - When the Health Care Worker Is Sick: Primum Non Nocere. PMID- 26148245 TI - Nonalcoholic fatty liver disease: a potential consequence of tumor necrosis factor-inhibitor therapy. AB - INTRODUCTION: Although tumor necrosis factor inhibitors (TNFi) might be expected to protect against nonalcoholic fatty liver disease (NAFLD), we have seen patients who appeared to develop NAFLD during TNFi treatment. We aimed to explore risk factors for this TNFi complication in a case-control study. METHODS: We reviewed clinic records at our VA hospital to identify patients with inflammatory diseases who developed aminotransferase elevations during TNFi therapy and who had liver biopsies showing NAFLD. These patients were matched with patients in each of three control groups: (i) inflammatory disease controls: patients on TNFi treatment with normal aminotransferase levels, (ii) nonalcoholic steatohepatitis (NASH) controls: patients with biopsy-proven NASH with no other inflammatory disease, and (iii) healthy controls. Genotyping was performed for PNPLA3, a gene predisposing to NASH. RESULTS: We identified eight cases (five steatohepatitis, three steatosis); elevated aminotransferase levels were first observed 1-63 months into TNFi therapy (average 12 months). TNFi therapy was stopped in five patients, whose aminotransferase levels then normalized within 2-8 months. There were no significant differences between cases and inflammatory disease controls in the frequency of features of metabolic syndrome. Cases had more methotrexate exposure than inflammatory controls (50 vs. 12.5%, P=0.28). PNPLA3 genotyping revealed mutations in 75% of cases, 38% of inflammatory controls, 88% of NASH controls, and 63% of healthy controls (P=NS). CONCLUSION: Our findings suggest that NAFLD can be a side effect of TNFi therapy, and that methotrexate exposure and PNPLA3 gene mutations might be risk factors. Further studies are needed to determine how TNFi causes NAFLD and to confirm these risk factors. PMID- 26148246 TI - Monocyte-derived dendritic cells in children with chronic hepatitis C: correlation with interferon and ribavirin therapy. AB - BACKGROUND: Hepatitis C virus (HCV) infection is a major health problem worldwide. Defective dendritic cell (DC) activation of T cells may underlie poor T-cell responsiveness in HCV infection. OBJECTIVE: To evaluate the DCs' functions in chronically infected HCV patients and its correlation with the response to therapy. PATIENTS AND METHODS: This prospective study included 30 chronic hepatitis C (CHC) patients and 30 healthy age-matched and sex-matched controls. The first group received combined pegylated interferon-alpha-2b (Peg-IFN alpha2b)/ribavirin therapy for 48 weeks. A quantitative HCV-RNA PCR was performed for all patients before treatment and at 12, 24, 48, and 24 weeks after treatment. To clarify the functions of DCs, we induced maturation of peripheral DCs from blood samples of CHC patients and healthy controls using Resiquimod (R848). The functions of DCs were assessed by measurement of the levels of IFN gamma and interleukin-10 (IL-10). RESULTS: Sixteen (53.3%) of the patients were treatment responders and the other 14 (46.4%) were nonresponders. The current study showed a statistically significant difference between CHC patients and the control group in IFN-gamma production, which was higher in the control group (1.53+/-0.38 IU/ml) than in the CHC patients (1.19+/-0.21 IU/ml); in contrast, IL 10 was higher in CHC (249.4+/-27.6 pg/ml) than the control group (217.0+/-29.9 pg/ml). However, there was no significant difference between treatment responders and nonresponders in both IFN-gamma and IL-10 levels. CONCLUSION: HCV infection is associated with impaired production of IFN-gamma, which may be an indication of a defect in DC function. PMID- 26148247 TI - The role of fiber supplementation in the treatment of irritable bowel syndrome: a systematic review and meta-analysis. AB - Irritable bowel syndrome (IBS) is a functional bowel disorder associated with a wide variety of clinical symptoms. The use of fiber in treatment of IBS is well established, but recent reviews have shown conflicting evidence. The aim of our review was to study the effects of fiber (soluble and insoluble) on the symptoms of IBS. Medline, EMBASE, Cochrane Central, CINAHL, LILACS, and ClinicalTrials.gov were searched for appropriate studies. Two reviewers screened the title/abstract and full text against the inclusion criterion - that is, randomized control trials/crossover studies that compare fiber with placebo for its effect on IBS in an outpatient setting. Independent double data extraction was performed across multiple fields. An assessment of the risk of bias and tests for heterogeneity were carried out, along with a meta-analysis of the outcomes of interest. The search yielded 4199 unique records: 121 were selected after title/abstract screening and 22 after full screening. There was moderate clinical, methodological, and statistical heterogeneity across studies, with a moderate risk of bias. Overall, there was a significant improvement in global assessment of symptoms among those randomized to fiber [risk ratio: 1.27; 95% confidence interval (CI): 1.05-1.54]. Soluble fiber improved assessment of symptoms (risk ratio 1.49; 95% CI: 1.09-2.03), as well as the abdominal pain score (mean difference: -1.84; 95% CI: -2.72 to -0.97), with insoluble fiber not showing improvement in any outcome. Soluble fiber appears to improve symptoms of IBS, whereas there is no evidence for recommending insoluble fiber for IBS. PMID- 26148248 TI - Autoimmune liver disease and concomitant extrahepatic autoimmune disease. AB - AIM: To assess the frequency and clinical impact of associated extrahepatic autoimmune diseases (EAD) on autoimmune liver diseases (ALD). PATIENTS AND METHODS: We investigated 608 patients with ALD (327 autoimmune hepatitis - AIH and 281 primary biliary cirrhosis - PBC) for concomitant EAD. RESULTS: In both AIH and PBC, we observed a high prevalence of EAD (29.9 and 42.3%, respectively); both diseases showed a significant association with autoimmune thyroid disease, followed by autoimmune skin disease, celiac disease, and vasculitis in AIH patients and sicca syndrome, CREST syndrome, and celiac disease in PBC patients. At diagnosis, AIH patients with concurrent EAD were more often asymptomatic than patients with isolated AIH (P<0.01). CONCLUSION: Our study confirms the strict association between ALD and EAD, in particular with autoimmune thyroid disease. In the light of our results, all patients with an EAD should be assessed for the concomitant presence of an asymptomatic ALD. PMID- 26148249 TI - Congenital acute megakaryoblastic leukemia. PMID- 26148250 TI - A Practical, Global Perspective on Using Administrative Data to Conduct Intensive Care Unit Research. AB - Various data sources can be used to conduct research on critical illness and intensive care unit (ICU) use. Most published studies derive from randomized controlled trials, large-scale clinical databases, or retrospective chart reviews. However, few investigators have access to such data sources or possess the resources to create them. Hospital administrative data, also called health claims data, constitute an important alternative data source that can be used to address a broad range of research questions, including many that would be difficult to study in interventional studies. Such data often contain information that allows identification of ICU care, specific types of critical illness, and ICU-related procedures. The strengths of using administrative databases are that many are population-based, cover broad geographic regions, and are large enough to provide high statistical power and precise effect estimates. Linking hospital data to other databases regarding chronic care facilities, home care services, or rehabilitation services, for example, can expand the scope of research questions that can be answered. However, the limitations of administrative data must be recognized. They are not collected for research purposes; thus, data elements may vary in accuracy, and key clinical variables such as ICU-specific physiologic and laboratory data are usually lacking. Specific efforts should be made to validate the data elements used, as has been done in several world regions. As with any other research question, it is imperative that the analysis plan be carefully defined in advance and that appropriate attention be paid to potential sources of bias and confounding. PMID- 26148253 TI - Images of the Month: MDMA-Induced Acute Liver Failure and Transient Abdominal Pneumatosis. PMID- 26148251 TI - Functional analysis of phosphorylation of the mitotic centromere-associated kinesin by Aurora B kinase in human tumor cells. AB - Mitotic centromere-associated kinesin (MCAK) is the best characterized member of the kinesin-13 family and plays important roles in microtubule dynamics during mitosis. Its activity and subcellular localization is tightly regulated by an orchestra of mitotic kinases, such as Aurora B. It is well known that serine 196 of MCAK is the major phosphorylation site of Aurora B in Xenopus leavis extracts and that this phosphorylation regulates its catalytic activity and subcellular localization. In the current study, we have addressed the conserved phosphorylation site serine 192 in human MCAK to characterize its function in more depth in human cancer cells. Our data confirm that S192 is the major phosphorylation site of Aurora B in human MCAK and that this phosphorylation has crucial roles in regulating its catalytic activity and localization at the kinetochore/centromere region in mitosis. Interfering with this phosphorylation leads to a delayed progression through prometa- and metaphase associated with mitotic defects in chromosome alignment and segregation. We show further that MCAK is involved in directional migration and invasion of tumor cells, and interestingly, interference with the S192 phosphorylation affects this capability of MCAK. These data provide the first molecular explanation for clinical observation, where an overexpression of MCAK was associated with lymphatic invasion and lymph node metastasis in gastric and colorectal cancer patients. PMID- 26148254 TI - Images of the Month: An Unusual Endoscopic Signature of Gastric Metaplasia. PMID- 26148255 TI - Images of the Month: Excavated Duodenal Gastrointestinal Stromal Tumor Diagnosed via Standard Endoscopic Biopsy. PMID- 26148256 TI - Images of the Month: Acute Pancreatitis in Gastric Aberrant Pancreas. PMID- 26148257 TI - Video of the Month: Endoscopic Drainage of Postoperative Collection After Robot Assisted Distal Pancreatectomy. PMID- 26148262 TI - Miles to Go on the SCENIC Route: Should Chromoendoscopy Become the Standard of Care in IBD Surveillance? AB - The recent SCENIC Consensus statement has raised questions about which patients with chronic colitis should receive chromoendoscopic surveillance. Two papers in this issue of the American Journal of Gastroenterology provide more evidence and context, and this editorial discusses the current evidence base, which patients might benefit from chromoendoscopy, and what more evidence is needed before chromoendoscopy can be considered a possible new standard of care in all patients with chronic colitis. PMID- 26148263 TI - Combination Therapy of Ursodeoxycholic Acid and Bezafibrate in Patients With Primary Biliary Cirrhosis: The End of the Steroid Era in Autoimmune Liver Diseases? PMID- 26148264 TI - Response to Licinio et al. PMID- 26148265 TI - Colonization With Toxicogenic C. difficile Upon Hospital Admission. PMID- 26148266 TI - Response to Matuchansky. [corrected]. PMID- 26148269 TI - Erratum: Incidence, Prevalence, and Temporal Trends of Microscopic Colitis: A Systematic Review and Meta-Analysis. PMID- 26148270 TI - Corrigendum: PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease. PMID- 26148271 TI - Reduced pain threshold documented in children with Down syndrome. PMID- 26148272 TI - Vascular Adventitia Calcification and Its Underlying Mechanism. AB - Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD) for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCs)were obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-beta1 (20 ng/ml) + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells. PMID- 26148273 TI - Challenges, benefits, and factors to enhance recruitment and inclusion of children in pediatric dental research. AB - BACKGROUND: Historically, children have been excluded from clinical research. Many drugs and procedures have not been tested on children. The International Conference on Harmonization and the Food and Drug Administration guidance now stress that children should be included in research unless there is a reason for exclusion. Compared to adults, recruitment of children at different life stages requires different considerations. OBJECTIVE: To review published studies and gray literature to identify pediatric recruitment strategies and develop recommendations. RESULTS: There is limited clinical research literature available to recommend recruitment strategies and methods for pediatric trials. Formal guidelines for reporting recruitment activities in publications are scant. Recommendations are made based on current practices regarding protocol design, obtaining consent and engaging child, parent and caregiver in research. CONCLUSIONS: A scientific approach is needed to determine the best design for recruitment of pediatric clinical studies. Investigators should report and publish recruitment and retention strategies that facilitate this important aspect of the research process to increase transparency, efficiency, and identification of the most effective methods for dental researchers. PMID- 26148274 TI - Effects of Early-Stage Group Psychoeducation Programme for Patients with Depression. AB - The purpose of this study was to examine the effect of a psychoeducational group programme on inpatients with depression. We compared the attributes and Inventory Scale for Mood and Sense of Fatigue (SMSF) scores of 45 people who participated in the programme (participation group) with those of 37 people who did not participate (control group). Further, we investigated the rate of readmission 6 months after discharge and the number of patients in the participation group who had consulted a psychiatric social worker. Statistically, there were no significant differences in the SMSF score between the two groups on admission and at the time of discharge. The programme had no effect on the readmission rate. However, the SMSF score of the participation group significantly improved from the start of the programme to patient discharge. Furthermore, improvement of depressive symptoms, feeling of recovery and adherence were found in the participation group. The programme seemed to provide a psychotherapeutic effect for the patients and promoted cooperation with occupational therapist and other specialists in the hospital. The efficacy of psychoeducation in preventing recurrence of depression remains to be demonstrated, and methods of investigating effective approaches for this purpose need to be considered in the future. PMID- 26148276 TI - Long-Term Prognosis After Coronary Artery Calcification Testing in Asymptomatic Patients: A Cohort Study. AB - BACKGROUND: The extent of coronary artery calcification (CAC) and near-term adverse clinical outcomes are strongly related through 5 years of follow-up. OBJECTIVE: To describe the ability of CAC scores to predict long-term mortality in persons without symptoms of coronary artery disease. DESIGN: Observational cohort. SETTING: Single-center, outpatient cardiology laboratory. PATIENTS: 9715 asymptomatic patients. MEASUREMENTS: Coronary artery calcification scoring and binary risk factor data were collected. The primary end point was time to all cause mortality (median follow-up, 14.6 years). Univariable and multivariable Cox proportional hazards models were used to compare survival distributions. The net reclassification improvement statistic was calculated. RESULTS: In Cox models adjusted for risk factors for coronary artery disease, the CAC score was highly predictive of all-cause mortality (P < 0.001). Overall 15-year mortality rates ranged from 3% to 28% for CAC scores from 0 to 1000 or greater (P < 0.001). The relative hazard for all-cause mortality ranged from 1.68 for a CAC score of 1 to 10 (P < 0.001) to 6.26 for a score of 1000 or greater (P < 0.001). The categorical net reclassification improvement using cut points of less than 7.5% to 22.5% or greater was 0.21 (95% CI, 0.16 to 0.32). LIMITATIONS: Data collection was limited to a single center with generalizability limitations. Only binary risk factor data were available, and CAC was only measured once. CONCLUSION: The extent of CAC accurately predicts 15-year mortality in a large cohort of asymptomatic patients. Long-term estimates of mortality provide a unique opportunity to examine the value of novel biomarkers, such as CAC, in estimating important patient outcomes. PRIMARY FUNDING SOURCE: None. PMID- 26148280 TI - Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis: A Systematic Review and Meta-analysis. AB - BACKGROUND: Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment remains challenging. PURPOSE: To assess evidence from randomized, controlled trials of the timing of ART initiation in HIV-infected adults with newly diagnosed pulmonary TB. DATA SOURCES: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts, and ClinicalTrials.gov (from January 1980 to May 2015). STUDY SELECTION: Randomized, controlled trials evaluating early versus delayed ART initiation (1 to 4 weeks vs. 8 to 12 weeks after initiation of TB treatment) or deferred ART initiation (after the end of TB treatment). DATA EXTRACTION: Three reviewers independently extracted data and assessed risk of bias. The main outcome measures were all-cause mortality and the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). DATA SYNTHESIS: The 8 included trials (n = 4568) were conducted in Africa, Asia, and the United States and were generally at low risk of bias for the assessed domains. Overall, early ART reduced mortality compared with delayed ART (relative risk [RR], 0.81 [95% CI, 0.66 to 0.99]; I2 = 0%). In a prespecified subgroup analysis, early ART reduced mortality compared with delayed ART among patients with baseline CD4+ T-cell counts less than 0.050 * 109 cells/L (RR, 0.71 [CI, 0.54 to 0.93]; I2 = 0%). However, a mortality benefit from early ART was not found among those with CD4+ T-cell counts greater than 0.050 * 109 cells/L (RR, 1.05 [CI, 0.68 to 1.61]; I2 = 56%). Early ART was associated with a higher incidence of TB-IRIS than delayed ART (RR, 2.31 [CI, 1.87 to 2.86]; I2 = 19%). LIMITATION: Few trials provided sufficient data for subgroup analysis. CONCLUSION: Early ART in HIV-infected adults with newly diagnosed TB improves survival in those with CD4+ T-cell counts less than 0.050 * 109 cells/L, although this is associated with a 2-fold higher frequency of TB-IRIS. In patients with CD4+ T-cell counts greater than 0.050 * 109 cells/L, evidence is insufficient to support or refute a survival benefit conferred by early versus delayed ART initiation. PRIMARY FUNDING SOURCE: None. (PROSPERO registration: CRD42012001884). PMID- 26148278 TI - Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study. AB - BACKGROUND: Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored. OBJECTIVE: To examine stroke risks associated with subclinical brain lesions (<3 mm only, >=3 mm only, and both sizes) and white matter hyperintensities (WMHs). DESIGN: Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study. SETTING: Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995. PARTICIPANTS: 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years. MEASUREMENTS: Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models. RESULTS: Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]). LIMITATION: Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes. CONCLUSION: Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute. PMID- 26148282 TI - Celebrating the ACP Centennial: From the Annals Archive--Smoking Cessation. PMID- 26148283 TI - On being a doctor. Letters. PMID- 26148284 TI - Effects of Blood Pressure Reduction in Mild Hypertension. PMID- 26148285 TI - Effects of Blood Pressure Reduction in Mild Hypertension. PMID- 26148286 TI - Calibration and Discrimination Among Multiple Cardiovascular Risk Scores in a Modern Multiethnic Cohort. PMID- 26148287 TI - Calibration and Discrimination Among Multiple Cardiovascular Risk Scores in a Modern Multiethnic Cohort. PMID- 26148288 TI - Use of Life-Sustaining Therapies for Patients With Ebola Virus Disease. PMID- 26148289 TI - Use of Life-Sustaining Therapies for Patients With Ebola Virus Disease. PMID- 26148290 TI - Anakinra Improves Pyoderma Gangrenosum in Psoriatic Arthritis: A Case Report. PMID- 26148292 TI - In the Clinic. Gastroesophageal Reflux Disease. AB - This issue provides a clinical overview of gastroesophageal reflux disease, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic. PMID- 26148293 TI - Web Exclusives. Annals Graphic Medicine: One in a Million. PMID- 26148294 TI - Cortisol and alpha-Amylase Secretion Patterns between and within Depressed and Non-Depressed Individuals. AB - OBJECTIVES: Associations between biological stress markers and depression are inconsistent across studies. We assessed whether inter- and intra-individual variability explain these inconsistencies. METHODS: Pair-matched depressed and non-depressed participants (N = 30) collected saliva thrice a day for 30 days, resulting in 90 measurements per individual. The relationships between measures of stress-system function and depression were examined at the group level by means of mixed model analyses, and at the individual level by means of pair matched comparisons. The analyses were repeated after adjusting for time-varying lifestyle factors by means of time-series regression analyses. RESULTS: Cortisol and alpha-amylase levels were higher, the alpha-amylase/cortisol ratio larger, and the daily cortisol slope steeper in the depressed compared to the non depressed group. Adjusting for lifestyle factors and antidepressant use reduced the associations under study. In 40%-60% of the matched comparisons, depressed individuals had higher cortisol and alpha-amylase levels, a larger alpha amylase/cortisol ratio, and a steeper daily slope than their non-depressed match, regardless of adjustment. CONCLUSIONS: Our group-level findings were mostly in line with the literature but generalization to individuals appeared troublesome. Findings of studies on this topic should be interpreted with care, because in clinical practice the focus is on individuals instead of groups. PMID- 26148295 TI - Motion Tree Delineates Hierarchical Structure of Protein Dynamics Observed in Molecular Dynamics Simulation. AB - Molecular dynamics (MD) simulations of proteins provide important information to understand their functional mechanisms, which are, however, likely to be hidden behind their complicated motions with a wide range of spatial and temporal scales. A straightforward and intuitive analysis of protein dynamics observed in MD simulation trajectories is therefore of growing significance with the large increase in both the simulation time and system size. In this study, we propose a novel description of protein motions based on the hierarchical clustering of fluctuations in the inter-atomic distances calculated from an MD trajectory, which constructs a single tree diagram, named a "Motion Tree", to determine a set of rigid-domain pairs hierarchically along with associated inter-domain fluctuations. The method was first applied to the MD trajectory of substrate-free adenylate kinase to clarify the usefulness of the Motion Tree, which illustrated a clear-cut dynamics picture of the inter-domain motions involving the ATP/AMP lid and the core domain together with the associated amplitudes and correlations. The comparison of two Motion Trees calculated from MD simulations of ligand-free and -bound glutamine binding proteins clarified changes in inherent dynamics upon ligand binding appeared in both large domains and a small loop that stabilized ligand molecule. Another application to a huge protein, a multidrug ATP binding cassette (ABC) transporter, captured significant increases of fluctuations upon binding a drug molecule observed in both large scale inter-subunit motions and a motion localized at a transmembrane helix, which may be a trigger to the subsequent structural change from inward-open to outward-open states to transport the drug molecule. These applications demonstrated the capabilities of Motion Trees to provide an at-a-glance view of various sizes of functional motions inherent in the complicated MD trajectory. PMID- 26148296 TI - Coupling Hydroxyapatite Nanocrystals with Lactoferrin as a Promising Strategy to Fine Regulate Bone Homeostasis. AB - Lactoferrin (LF) is an interesting glycoprotein in the field of bone biology for its regulatory effect on cells involved in bone remodeling, that results compromised in several pathological conditions, as osteoporosis. In a previous study we observed that the coupling of LF and biomimetic hydroxyapatite nanocrystals (HA), a material well-known for its bioactivity and osteoconductive properties, leads to a combined effect in the induction of osteogenic differentiation of mesenchymal stem cells. On the basis of this evidence, the present study is an extension of our previous work aiming to investigate the synergistic effect of the coupling of HA and LF on bone homeostasis. Biomimetic HA nanocrystals were synthesized and functionalized with LF (HA-LF) and then pre osteoblasts (MC3T3-E1) and monocyte/macrophage cells lines (RAW 264.7), using as osteoclastogenesis in vitro model, were cultured separately or in co-culture in presence of HA-LF. The results clearly revealed that HA and LF act in synergism in the regulation of the bone homeostasis, working as anabolic factor for osteoblasts differentiation and bone matrix deposition, and as inhibitor of the osteoclast formation and activity. PMID- 26148298 TI - Aging With Rising Risk: Have Older Households Experienced Faster-Growing Risk Exposure Than Younger Ones Since the 1990s? AB - Financial markets have been characterized by boom and bust cycles since the 1980s, while the responsibility for managing retirement wealth has increasingly shifted onto individual households at the same time. Policy makers and experts have expressed concern over rising risk exposure among older householders, who appear to be increasingly exposed to the growing financial risks just as they near retirement. We consider household data from the Federal Reserve's Survey of Consumer Finances from 1989 to 2010 to analyze the correlation between age and risk exposure. We test whether older householders' risk exposure has indeed grown over time, whether it has increased more than that of younger householders, whether changes in the demographic composition of older householders have contributed to older households' rising risk exposure, and the degree to which increases in risk exposure can be traced to a growing concentration of household assets held in stocks and housing and to rising householder indebtedness. Our results indicate that risk exposure has grown more for older householders than for younger ones, that demographic changes among older householders have contributed to additional increases in older householders' risk exposure, and that the growth of older householders' risk exposure is driven more by rising risky asset concentration and less by greater indebtedness. PMID- 26148297 TI - In vivo treatment with the NF-kappaB inhibitor ursodeoxycholic acid (UDCA) improves tension development in the isolated mdx costal diaphragm. AB - INTRODUCTION: Previous experiments have indicated that in vivo administration of ursodeoxycholic acid (UDCA) inhibits nuclear NF-kappaB activation and has beneficial effects on the structure and function of dystrophic (mdx) muscle. We examined the effect of UDCA on tension development in dystrophic muscle. METHODS: Isometric tension development was examined in costal diaphragms that were freshly isolated from vehicle and UDCA treated mdx mice. Percent recovery scores were obtained by directly comparing these measurements to those obtained from age matched nondystrophic mice. RESULTS: Vehicle treated mdx mice exhibited significantly reduced optimal muscle lengths (lo ) and specific twitch and tetanic tensions compared with age-matched nondystrophic mice. UDCA treated preparations exhibited significantly improved tension development with a 33% recovery score. CONCLUSIONS: Because UDCA is used in treating certain clinical disorders, these results provide a rationale for human clinical trials using this and related drugs for treatment of Duchenne and related muscular dystrophies. PMID- 26148299 TI - Underwater Noise from a Wave Energy Converter Is Unlikely to Affect Marine Mammals. AB - Underwater noise was recorded from the Wavestar wave energy converter; a full scale hydraulic point absorber, placed on a jack-up rig on the Danish North Sea coast. Noise was recorded 25 m from the converter with an autonomous recording unit (10 Hz to 20 kHz bandwidth). Median sound pressure levels (Leq) in third octave bands during operation of the converter were 106-109 dB re. 1 MUPa in the range 125-250 Hz, 1-2 dB above ambient noise levels (statistically significant). Outside the range 125-250 Hz the noise from the converter was undetectable above the ambient noise. During start and stop of the converter a more powerful tone at 150 Hz (sound pressure level (Leq) 121-125 dB re 1 MUPa) was easily detectable. This tone likely originated from the hydraulic pump which was used to lower the absorbers into the water and lift them out of the water at shutdown. Noise levels from the operating wave converter were so low that they would barely be audible to marine mammals and the likelihood of negative impact from the noise appears minimal. A likely explanation for the low noise emissions is the construction of the converter where all moving parts, except for the absorbers themselves, are placed above water on a jack-up rig. The results may thus not be directly transferable to other wave converter designs but do demonstrate that it is possible to harness wave energy without noise pollution to the marine environment. PMID- 26148300 TI - Triads in Ophthalmology: A Comprehensive Review. AB - Ophthalmology, like any other clinical science, is constantly evolving. As our knowledge in this field expands, we enumerate and describe classical triads of symptoms or signs with relevance to ophthalmology in this article. Characteristic clinical triads for certain systemic conditions with ocular implications are also discussed. PMID- 26148302 TI - Enhanced Lifetime of Polymer Solar Cells by Surface Passivation of Metal Oxide Buffer Layers. AB - The role of electron selective interfaces on the performance and lifetime of polymer solar cells were compared and analyzed. Bilayer interfaces consisting of metal oxide films with cationic polymer modification namely poly ethylenimine ethoxylated (PEIE) were found to enhance device lifetime compared to bare metal oxide films when used as an electron selective cathode interface. Devices utilizing surface-modified metal oxide layers showed enhanced lifetimes, retaining up to 85% of their original efficiency when stored in ambient atmosphere for 180 days without any encapsulation. The work function and surface potential of zinc oxide (ZnO) and ZnO/PEIE interlayers were evaluated using Kelvin probe and Kelvin probe force microscopy (KPFM) respectively. Kelvin probe measurements showed a smaller reduction in work function of ZnO/PEIE films compared to bare ZnO films when aged in atmospheric conditions. KPFM measurements showed that the surface potential of the ZnO surface drastically reduces when stored in ambient air for 7 days because of surface oxidation. Surface oxidation of the interface led to a substantial decrease in the performance in aged devices. The enhancement in the lifetime of devices with a bilayer interface was correlated to the suppressed surface oxidation of the metal oxide layers. The PEIE passivated surface retained a lower Fermi level when aged, which led to lower trap-assisted recombination at the polymer-cathode interface. Further photocharge extraction by linearly increasing voltage (Photo-CELIV) measurements were performed on fresh and aged samples to evaluate the field required to extract maximum charges. Fresh devices with a bare ZnO cathode interlayer required a lower field than devices with ZnO/PEIE cathode interface. However, aged devices with ZnO required a much higher field to extract charges while aged devices with ZnO/PEIE showed a minor increase compared to the fresh devices. Results indicate that surface modification can act as a suitable passivation layer to suppress oxidation in metal oxide thin films for enhanced lifetime in inverted organic solar cells. PMID- 26148301 TI - The Impact of E-Learning on Adherence to Guidelines for Acute Gastroenteritis: A Single-Arm Intervention Study. AB - OBJECTIVE: E-learning is a candidate tool for clinical practice guidelines (CPG) implementation due to its versatility, universal access and low costs. We aimed to assess the impact of a five-module e-learning course about CPG for acute gastroenteritis (AGE) on physicians' knowledge and clinical practice. STUDY DESIGN: This work was conceived as a pre/post single-arm intervention study. Physicians from 11 European countries registered for the online course. Personal data, pre- and post-course questionnaires and clinical data about 3 to 5 children with AGE managed by each physician before and after the course were collected. Primary outcome measures included the proportion of participants fully adherent to CPG and number of patients managed with full adherence. RESULTS: Among the 149 physicians who signed up for the e-learning course, 59 took the course and reported on their case management of 519 children <5 years of age who were referred to their practice because of AGE (281 and 264 children seen before and after the course, respectively). The course improved knowledge scores (pre-course 8.6 +/- 2.7 versus post-course 12.8 +/- 2.1, P < 0.001), average adherence (from 87.0 +/- 7.7% to 90.6 +/- 7.1%, P = 0.001) and the number of patients managed in full adherence with the guidelines (from 33.6 +/- 31.7% to 43.9 +/- 36.1%, P = 0.037). CONCLUSIONS: E-learning is effective in increasing knowledge and improving clinical practice in paediatric AGE and is an effective tool for implementing clinical practice guidelines. PMID- 26148303 TI - Allosteric transitions of ATP-binding cassette transporter MsbA studied by the adaptive anisotropic network model. AB - The transporter MsbA is a kind of multidrug resistance ATP-binding cassette transporter that can transport lipid A, lipopolysaccharides, and some amphipathic drugs from the cytoplasmic to the periplasmic side of the inner membrane. In this work, we explored the allosteric pathway of MsbA from the inward- to outward facing states during the substrate transport process with the adaptive anisotropic network model. The results suggest that the allosteric transitions proceed in a coupled way. The large-scale closing motions of the nucleotide binding domains occur first, accompanied with a twisting motion at the same time, which becomes more obvious in middle and later stages, especially for the later. This twisting motion plays an important role for the rearrangement of transmembrane helices and the opening of transmembrane domains on the periplasmic side that mainly take place in middle and later stages respectively. The topological structure plays an important role in the motion correlations above. The conformational changes of nucleotide-binding domains are propagated to the transmembrane domains via the intracellular helices IH1 and IH2. Additionally, the movement of the transmembrane domains proceeds in a nonrigid body, and the two monomers move in a symmetrical way, which is consistent with the symmetrical structure of MsbA. These results are helpful for understanding the transport mechanism of the ATP-binding cassette exporters. PMID- 26148304 TI - Vitamin D, inflammation, and relations to insulin resistance in premenopausal women with morbid obesity. AB - OBJECTIVE: In this study, the associations between vitamin D, insulin sensitivity, and inflammation and their relationships with adipose tissue expression of vitamin D receptor (VDR) and inflammatory markers in women with morbid obesity were determined. METHODS: An oral glucose tolerance test prior to surgery was completed by healthy premenopausal women (n = 76) seeking bariatric surgery. Abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were collected during surgery. RESULTS: Approximately, 70% of our subjects were vitamin D sufficient or optimal, and 80% had normal glucose tolerance. No significant association between serum 25-hydroxyvitamin D [25(OH)D] with circulating inflammatory markers or insulin sensitivity was identified. In subjects with waist circumference of <139 cm (n = 42), log25(OH)D positively predicted VAT logIL-6 mRNA expression (P = 0.003). LogVDR expression was positively correlated with the expression of inflammatory markers in both SAT (logIL-1beta mRNA: r = 0.95, P < 0.0001; logTNF mRNA: r = 0.82, P < 0.0001) and VAT (logIL-1beta mRNA: r = 0.89, P < 0.0001; logTNF mRNA: r = 0.75, P < 0.0001). VAT logVDR expression positively predicted logHOMA-IR in non-African American subjects (P = 0.05). CONCLUSIONS: The beneficial effects of vitamin D on inflammation and insulin sensitivity were not supported by our findings. VDR does not appear to possess a protective effect in adipose tissue. PMID- 26148306 TI - Understanding time use, stress and recovery practices among early career physicians: an exploratory study. AB - Early career physicians (ECPs) work an average of 80 h per week, and at times may approach 24 continuous hours working. These hours, combined with a stressful work environment, and an inability to physically and psychologically detach from work make ECPs likely to experience burnout and other negative health-related consequences. This study provides insight into the stress and recovery challenges faced by ECPs in a typical hospital environment. Rich qualitative and quantitative data were gathered from participants regarding daily time usage, and recovery practices and needs. ECPs report longer working hours, less leisure time and shorter amounts of sleep than average working adults. ECPs do not participate in many resource-replenishing activities while at work, and when out of work, they tend to participate in more passive than active forms of recovery. Resource draining activities were identified as requiring much of ECP's nonwork time, further limiting recovery. The prevention of burnout and other negative health consequences among ECPs requires the building of a workplace and educational culture that supports regular resource replenishment. This includes the need for a curriculum of medical education that teaches ECPs to identify the signs of stress and recovery needs, and how to effectively address these needs. PMID- 26148305 TI - Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants. PMID- 26148307 TI - Photobioreactors for microalgal cultures: A Lagrangian model coupling hydrodynamics and kinetics. AB - Closed photobioreactors have to be optimized in terms of light utilization and overall photosynthesis rate. A simple model coupling the hydrodynamics and the photosynthesis kinetics has been proposed to analyze the photosynthesis dynamics due to the continuous shuttle of microalgae between dark and lighted zones of the photobioreactor. Microalgal motion has been described according to a stochastic Lagrangian approach adopting the turbulence model suitable for the photobioreactor configuration (single vs. two-phase flows). Effects of light path, biomass concentration, turbulence level and irradiance have been reported in terms of overall photosynthesis rate. Different irradiation strategies (internal, lateral and rounding) and several photobioreactor configurations (flat, tubular, bubble column, airlift) have been investigated. Photobioreactor configurations and the operating conditions to maximize the photosynthesis rate have been pointed out. Results confirmed and explained the common experimental observation that high concentrated cultures are not photoinhibited at high irradiance level. PMID- 26148308 TI - The meaning and implication of sun protection factor. PMID- 26148309 TI - A flexible, preclinical, medical school curriculum increases student academic productivity and the desire to conduct future research. AB - In 2006, small blocks of flexible curriculum time, termed selectives, were implemented in the Mayo Medical School preclinical curriculum. Selectives permitted students to pursue professional endeavors, such as research, service, and career exploration, in the preclinical years. The purpose of this study was to survey current and former Mayo medical students regarding the impact of selectives on their research interest and productivity. The authors surveyed 377 current and former Mayo Medical School students from the 2004 to 2014 graduating classes, 154 participants (41% response rate) responded to the survey. The classes were grouped into pre- and postselective groups for the comparison studies. Postselective students published significantly more (p = 0.003) and gave significantly more presentations (p = 0.0007) during medical school than preselective students. Thirty-four (72% of the postselective respondents) indicated that selectives had a strong or very strong impact on their current research interest. Respondents spent an average of 4.0 [3.0-5.0] weeks of Selective time on research, resulting in 1.8 [1.4-2.2] publications and 1.8 [1.4 2.2] presentations, which represented 52.5% [40.0-65.0%] and 47.3% [37.1-57.4%] of the students' total medical school publications and presentations, respectively. Flexible selective time during the preclinical years results in significantly more medical student academic productivity. PMID- 26148310 TI - Skin disorders in elderly subjects. AB - BACKGROUND: Skin problems in the elderly population have rarely been the subject of scientific research. OBJECTIVES: The present study aimed to determine the prevalences of the most common dermatological conditions in elderly subjects and to investigate their associations with systemic diseases. METHODS: The study involved a group of 198 consecutive patients aged >= 65 years who were admitted to the Departments of Dermatology and Geriatrics at the study institution. All participants were thoroughly evaluated in a clinical interview and physical examination in which special emphasis was placed on dermatological issues. RESULTS: All subjects presented at least one dermatological condition. A significant correlation was found between the number of systemic diseases and the number of different skin lesions observed. The most common skin disorders included solar lentigines, senile angiomas, xerosis, seborrheic warts, varicose veins, edema of the lower legs, and pruritus. Patients aged >= 75 years demonstrated solar lentigines, edema of the lower legs, clavi, solar keratoses, and onychomycosis significantly more often, whereas patients aged < 75 years suffered more frequently from psoriasis. Diabetes was associated with the development of onychomycosis; hypercholesterolemia promoted the incidence of xanthomas and drug-induced skin reactions; chronic obstructive pulmonary disease was associated with senile purpura; and hypothyroidism favored the occurrence of varicose veins in the lower legs and telogen effluvium. CONCLUSIONS: Skin disorders are common in elderly people. Systemic diseases promote the development of dermatological conditions. A comprehensive approach to health problems in elderly subjects requires knowledge of dermatology. PMID- 26148311 TI - The Ars Moriendi Model for Spiritual Assessment: A Mixed-Methods Evaluation. AB - PURPOSE/OBJECTIVES: To explore nurses' and physicians' experiences with the ars moriendi model (AMM) for spiritual assessment. DESIGN: Convergent, parallel, mixed-methods. SETTING: Palliative home care in Belgium. SAMPLE: 17 nurses and 4 family physicians (FPs) in the quantitative phase, and 19 nurses and 5 FPs in the later qualitative phase. METHODS: A survey was used to investigate first impressions after a spiritual assessment. Descriptive statistics were applied for the analysis of the survey. In a semistructured interview a few weeks later, nurses and physicians were asked to describe their experiences with using the AMM. Interviews were audio recorded, transcribed, and qualitatively analyzed. Quantitative and qualitative results were compared to see whether the findings were confirmative. MAIN RESEARCH VARIABLES: The survey assessed the feasibility of the AMM for use in palliative home care, whereas the semistructured interviews collected in-depth descriptions of healthcare providers' (HCPs') experiences with the AMM. FINDINGS: The AMM was perceived as valuable. Many patients shared their wishes and expectations about the end of life. Most HCPs said they felt that the patient-provider relationship had been strengthened as a result of the spiritual assessment. Almost all assessments raised new issues; however, many dyads had informally discussed spiritual issues before. CONCLUSIONS: The current study suggests that HCPs believe that the AMM is a useful spiritual assessment tool. Guided by the model, HCPs can gather information about the context, life story, and meaningful connections of patients, which enables them to facilitate person centered care. IMPLICATIONS FOR NURSING: The AMM appears to be an important tool for spiritual assessment that can offer more insight into patients' spirituality and help nurses to establish person-centered end-of-life care. PMID- 26148312 TI - The Trouble With Teen and Young Adult Cancer Care. PMID- 26148313 TI - Balancing Illness and Parental Demands: Coping With Cancer While Raising Minor Children. AB - PURPOSE/OBJECTIVES: To explore the cancer experience of parents and their perceptions of supportive strategies to assist them with illness- and family related challenges. DESIGN: Qualitative, descriptive design. SETTING: A large McGill University-affiliated hospital cancer care center in Montreal, Quebec, Canada. PARTICIPANTS: Five mothers and seven fathers aged 33-67 years with a first cancer diagnosis who received treatment at the cancer clinic within the previous year. Participants had to have at least one minor child living with them. METHODOLOGIC APPROACH: Semistructured, audio-recorded interviews. FINDINGS: Three main categories emerged. CONCLUSIONS: Coping with cancer while raising children requires delicate balancing of illness and parenting demands. Tangible support systems must include access to childcare services, home healthcare services, and transportation solutions. INTERPRETATION: Support for parenting needs is a key component of comprehensive cancer care. Oncology nurses should stay informed of all hospital, clinic, and community resources to facilitate access for parents. Unmet support needs indicate that improvements need to be made in access to medical appointments around family schedules, expanded resources for children, and reduction of wait times. PMID- 26148314 TI - Resistance Exercise Reduces Body Fat and Insulin During Androgen-Deprivation Therapy for Prostate Cancer. AB - PURPOSE/OBJECTIVES: To determine whether exercise could reduce biomarkers of cancer progression in prostate cancer survivors (PCSs) on androgen-deprivation therapy (ADT). DESIGN: Randomized, controlled trial. SETTING: Oregon Health and Science University School of Nursing. SAMPLE: 51 PCSs randomized to one year of resistance and impact training or a stretching control group. METHODS: The authors investigated changes in body composition and cancer-related biomarkers, and the influence of age and fat loss on changes in biomarkers. MAIN RESEARCH VARIABLES: Body composition (total fat, trunk fat, and lean mass), insulin, insulin-like growth factor-1, and sex hormone-binding globulin. FINDINGS: In the 36 PCSs with baseline and 12-month data, total fat (p = 0.02) and trunk fat (p = 0.06) mass decreased in the training group compared to gains in controls. Loss of total and trunk fat each mediated the relationship between groups and one-year change in insulin (p < 0.05). Age moderated the insulin response to exercise where insulin reductions were smaller with increasing age (p = 0.03). CONCLUSIONS: Resistance and impact exercise may reduce body fat among PCSs undergoing ADT, in turn exerting an insulin-lowering effect. IMPLICATIONS FOR NURSING: Nurses should counsel PCSs to exercise to reduce the risk of obesity and associated conditions, including cancer progression. PMID- 26148315 TI - A Motivational, Gender-Sensitive Smoking Cessation Resource for Family Members of Patients With Lung Cancer. AB - PURPOSE/OBJECTIVES: To gather feedback on an innovative gender-sensitive booklet that draws on emotional connections and relationship factors to motivate smoking cessation. RESEARCH APPROACH: Qualitative, descriptive. SETTING: Six provinces in Canada. PARTICIPANTS: 30 family members of patients with lung cancer who were currently smoking or had recently quit. METHODOLOGIC APPROACH: Parallel booklets for women and men were developed using language and images to emphasize family relationships and gender considerations to motivate smoking cessation. Participants were provided with the women's and men's versions of the resource, and they were asked to review the gender-specific version of the booklet that was relevant to them. Semistructured telephone interviews were conducted, and transcriptions were analyzed for themes. FINDINGS: Three themes were evident in the data, including "new perspectives. CONCLUSIONS: A gender-sensitive approach that focuses on relationship factors represents an acceptable way to engage relatives of patients with lung cancer in discussions to support smoking cessation. INTERPRETATION: Approaches to supporting smoking cessation among relatives of patients diagnosed with lung cancer should draw on positive relationship bonds and caring connections to motivate cessation. PMID- 26148316 TI - Sleep Patterns During Hospitalization Following Hematopoietic Stem Cell Transplantation. AB - PURPOSE/OBJECTIVES: To characterize patient-reported and objective sleep assessments and provide a preliminary examination of the relationships among sleep, quality of life, and demographic or treatment factors. DESIGN: A secondary data analysis using a descriptive-correlational design. SETTING: University of Illinois Hospital and Health Sciences System. SAMPLE: 40 patients undergoing a hematopoietic stem cell transplantation (HCT) hospitalized for the conditioning regimen, stem cell infusion, and immediate recovery period. METHODS: Each patient wore a wrist actigraph continuously from the fourth day following HCT to the eighth day to objectively assess sleep patterns (total sleep time, sleep onset latency, sleep efficiency, wake after sleep onset, and number of awakenings). At the end of the five-day period, patients completed measures of sleep disturbance and quality of life. MAIN RESEARCH VARIABLES: Objective sleep (total sleep time, sleep onset latency, sleep efficiency, wake after sleep onset, and number of awakenings), subjective sleep (sleep disturbance), and quality of life. FINDINGS: The mean total nighttime sleep (objectively obtained) was 232 minutes (SD = 71 minutes), with 14 patients (35%) sleeping less than three consecutive hours during one or more study days. Age was negatively correlated with patient reported sleep disturbance. Patient-reported sleep disturbance was significantly associated with length of hospital stay. No correlations were found between patient-reported and objective sleep assessments. CONCLUSIONS: This study objectively documents inadequate and irregular sleep in hospitalized patients undergoing HCT. Sole reliance on patient-reported sleep assessments may not represent the full extent of the problem. IMPLICATIONS FOR NURSING: Attempts to streamline care during the night by not waking patients for routine care unless indicated by the patient's condition (as advocated by the American Academy of Nursing) and providing supportive care for symptoms (such as diarrhea) during the night may reduce the number of awakenings and possibly improve overall sleep quality. PMID- 26148317 TI - A Structured Nursing Intervention to Address Oral Chemotherapy Adherence in Patients With Non-Small Cell Lung Cancer. AB - PURPOSE/OBJECTIVES: To evaluate a nurse-led intervention to enhance medication knowledge and adherence using the Multinational Association for Supportive Care in Cancer Oral Agent Teaching Tool (MOATT). DESIGN: Longitudinal, descriptive feasibility study. SETTING: An ambulatory thoracic oncology disease center located at the Dana-Farber Cancer Institute in Boston, MA. SAMPLE: 30 adult patients with lung cancer who received the oral agent erlotinib. METHODS: Structured, nurse-led education sessions using the MOATT were provided, with a 72 hour follow-up telephone contact. Participants completed a Knowledge Rating Scale (KRS) and adapted Morisky Medication Adherence Scale-8 (MMAS-8) at the end of the first cycle of oral chemotherapy. MAIN RESEARCH VARIABLES: Knowledge and adherence; feasibility. FINDINGS: Twenty-seven participants completed the study outcome measures reporting high knowledge levels and MMAS-8 scores. Structured, nurse-led education and follow-up monitoring sessions ranged from 14-30 minutes. Several participants also initiated contact for assistance with prescription procurement and symptom management. Participants reported a median of two side effects. CONCLUSIONS: The structured, nurse-led teaching, using the MOATT tool, and follow-up nurse contacts were feasible as integrated into the thoracic oncology setting. Adherence and knowledge outcomes were encouraging. Additional studies should include objective adherence measures and strategies for delivering supportive care to patients at home. IMPLICATIONS FOR NURSING: Structured teaching with patients is important to enhance proper oral anticancer medication knowledge and adherence, including follow-up monitoring of administration and side effects at 72 hours. PMID- 26148318 TI - Healthcare Providers' Perceptions of the Utility of Psychosocial Screening Tools in Childhood Cancer: A Pilot Study. AB - PURPOSE/OBJECTIVES: To examine the perceptions of healthcare providers (HCPs) regarding the utility of two psychosocial screening tools designed for pediatric oncology, the Psychosocial Assessment Tool-Revised (PATrev) and the Psychosocial Care Checklist (PCCL). DESIGN: Repeated measures comparative study. SETTING: Four pediatric health centers in Ontario, Canada. SAMPLE: 15 oncologists, 14 nurses, and 8 social workers. METHODS: Using a visual analog scale (VAS), participants were asked to rate how useful they found (a) the psychosocial summary derived from the parent-completed PATrev, used to assess family psychosocial risk, and (b) the HCP-completed PCCL, used to identify family psychosocial needs. Measures were completed soon after diagnosis and six months later. Mann-Whitney U tests were used for analyses. MAIN RESEARCH VARIABLE: VAS scores. FINDINGS: Pediatric oncology HCPs differ in their acceptance of the psychosocial screening tools tested. The highest utility ratings for both instruments were from nurses, and the lowest utility ratings were from social workers; moderate ratings were obtained from oncologists. CONCLUSIONS: Psychosocial screening tools can identify the psychosocial needs of children with cancer and their families throughout the cancer trajectory. Consequently, these tools could foster communication among colleagues (medical and nonmedical) who are caring for children with cancer about the psychosocial needs of this population and the allocation of resources to address those needs. IMPLICATIONS FOR NURSING: Nurses seem to value these tools more than other HCPs, which may have positive implications for their clinical practice. PMID- 26148320 TI - Nursing Intervention Research. PMID- 26148319 TI - A Qualitative Study Exploring the Perceptions of Sedentary Behavior in Prostate Cancer Survivors Receiving Androgen-Deprivation Therapy. AB - PURPOSE/OBJECTIVES: To describe and understand the perceptions of sedentary behavior (SED) and the interests and preferences for a SED intervention of men on androgen-deprivation therapy (ADT) within a two-phase (formative and intervention research) feasibility study. RESEARCH APPROACH: Qualitative, descriptive. SETTING: Princess Margaret Cancer Centre and Odette Cancer Centre, both in Toronto, Ontario, Canada. PARTICIPANTS: 27 men on ADT. METHODOLOGIC APPROACH: Men were recruited from prostate cancer clinics. Nine focus groups were conducted from November 2013 to April 2014 until data saturation was reached. Probe questions assessed perceptions regarding SED and preferences for a mobile SED intervention. Data were transcribed verbatim, and a thematic analysis was conducted. FINDINGS: Twenty-seven men with a mean age of 73.5 years (SD = 8.1 years) volunteered for the study. Most men were aware of the health risks associated with SED, but most discussed SED in terms of increasing physical activity (PA). Many men were interested in a mobile application to reduce SED and expressed that the design should be easy to use, have an alerting function to interrupt sitting, have the ability to track and monitor PA levels, be tailored to the individual, and involve social support. CONCLUSIONS: These findings will inform the development and evaluation of a novel SED intervention to improve health outcomes in this population. INTERPRETATION: Oncology nurses may serve as a motivational factor in encouraging men on ADT to reduce SED. PMID- 26148321 TI - An Inpatient Surgical Oncology Unit's Experience With Moral Distress: Part II. PMID- 26148322 TI - Nursing Management of Sustained Rigors and Recurrent Fever as Symptoms of Filgrastim Hypersensitivity: A Case Report. PMID- 26148323 TI - Genetic Variants Influencing Patient Response to Opioid Therapy. PMID- 26148324 TI - Patient Satisfaction With Information Sharing. PMID- 26148325 TI - Trajectories of Obesity and Overweight Rates Among Survivors of Childhood Acute Lymphoblastic Leukemia. AB - PURPOSE/OBJECTIVES: To describe the trajectories of obesity/overweight rates by age group among survivors of childhood acute lymphoblastic leukemia (ALL) from diagnosis through several years post-therapy. DESIGN: Longitudinal, descriptive. SETTING: Hematology/oncology clinic in the southwestern United States. SAMPLE: 62 child and adolescent ALL survivors receiving treatment and follow-up care from 1999-2013. METHODS: Retrospective chart review of height, weight, and body mass index. MAIN RESEARCH VARIABLES: Annual obesity/overweight rates and developmental age groups. FINDINGS: Different trajectories of obesity/overweight rates existed among age groups. Forty-seven percent of adolescents met the Centers for Disease Control and Prevention criteria for obesity/overweight status at some point following diagnosis, compared to 68% of school-age and 73% of preschool children. Preschool children demonstrated the most rapid rate increase following diagnosis, with a particularly susceptible period in the years immediately following therapy. Obesity/overweight persistence was most characteristic of school-age children. CONCLUSIONS: Important variations in rate and pattern of weight status trajectories exist by age group, demonstrating that children diagnosed with ALL during the preschool and school-age developmental years have the greatest vulnerability of developing obesity/overweight status. IMPLICATIONS FOR NURSING: Obesity/overweight prevention efforts are greatly needed in children with ALL, and efforts should occur before ALL treatment completion in preschool and school age children. PMID- 26148326 TI - The Value of Fatigue Severity to Rule Out Depression in Older Adult Patients With Cancer. AB - PURPOSE/OBJECTIVES: To evaluate whether fatigue severity can serve as a cue to investigate the presence of depression in older adult patients with cancer. DESIGN: Cross-sectional observational cohort study. SETTING: Seven hospitals and general practices in Belgium and the Netherlands. SAMPLE: 205 older adult patients with cancer and 436 older adults without cancer (aged 70 years or older). METHODS: The diagnostic accuracy of fatigue as a proxy for depression was evaluated using sensitivity, specificity, and predictive values. MAIN RESEARCH VARIABLES: Fatigue was measured with a visual analog scale, and depression was measured with the 15-item Geriatric Depression Scale. FINDINGS: Fifty-six percent of the population experienced fatigue, and 13% were depressed. For fatigue as a cue for depression, sensitivity was 82%, specificity was 47%, positive predictive value was 18%, and negative predictive value was 95%. CONCLUSIONS: The data confirm that fatigue is a valuable cue to investigate the presence of depression because 82% of depressed participants were correctly identified by fatigue. The assessment of fatigue severity is intuitive, quick, straightforward, and usually already implemented. IMPLICATIONS FOR NURSING: Identification of depression is difficult in older adult patients with cancer. Instead of experiencing affective symptoms of depression, older adult patients are more likely to disclose somatic symptoms, such as fatigue, which often overlap with cancer-related symptoms. Nurses should be aware of this problem and should be alert for the possibility of depression in older adult patients presenting with fatigue. PMID- 26148327 TI - Effect of a Nurse-Led Psychoeducational Intervention on Healthcare Service Utilization Among Adults With Advanced Cancer. AB - PURPOSE/OBJECTIVES: To examine differences in healthcare service utilization among patients with advanced cancer participating in a nurse-led psychoeducational intervention. DESIGN: Secondary analysis of trial data. SETTING: Four Michigan cancer centers. SAMPLE: 484 patients with advanced cancer. METHODS: Patients were randomized to three groups. MAIN RESEARCH VARIABLES: Study arm (brief, extensive, or control), ED visitation (one or more times versus none), inpatient hospitalizations (one or more times versus none), and covariates. FINDINGS: No significant differences in ED visits or inpatient hospitalizations were observed among study arms. ED visits were more frequent for patients with lung or colorectal cancer, more comorbidities, and lower baseline QOL. Baseline QOL was associated with inpatient hospitalizations in the adjusted analysis. CONCLUSIONS: The psychoeducational intervention, either in brief or extensive format, is unlikely to increase healthcare service utilization. IMPLICATIONS FOR NURSING: Efficacious nurse-led psychoeducational interventions to improve QOL do not place undue burdens on the healthcare system and may improve care. PMID- 26148328 TI - Letter from the Editor. PMID- 26148330 TI - My passion is to drive innovation in vaccine development. PMID- 26148332 TI - Erratum. PMID- 26148331 TI - The expression of B & T cell activation markers in children's tonsils following live attenuated influenza vaccine. AB - Live attenuated influenza vaccines (LAIV) can prevent influenza illness and death in children. The absence of known correlates of protection induced by LAIV requires human studies of underlying mechanisms of vaccine-induced immunity, to further elucidate the immunological processes occurring. In this study, children scheduled for elective tonsillectomy were enrolled in a clinical trial to evaluate the immune response to LAIV, in order to compare T and B cell gene expression profiles. Twenty-three children (aged 3-17 years) were divided into 4 groups; unvaccinated controls, or vaccinated intranasally with LAIV at days 3-4, 6-7, and 12-15 before tonsillectomy. Total RNA extraction was performed on tonsillar tissue and high RNA quality was assured. The samples were then analyzed using a validated RT2 Profiler PCR Array containing 84 gene-specific primers involved in B and T cell activation, proliferation, differentiation, regulation and polarization. The gene expression after LAIV vaccination was subsequently compared to the controls. We observed that at d 3-4 post vaccination, 6 genes were down-regulated, namely APC, CD3G, FASLG, IL7, CD8A and TLR1. Meanwhile at 6 7 days post vaccination, 9 genes were significantly up-regulated, including RIPK2, TGFB1, MICB, SOCS1, IL2RA, MS4A1, PTPRC, IL2 and IL8. By days 12-15 the genes RIPK2, IL4, IL12B and TLR2 were overexpressed. RIPK2 was upregulated at all 3 time points. Our data suggests an overall proliferation, differentiation and regulation of B and T cells in the tonsils following LAIV, where the majority of genes were up-regulated at days 6-7 and normalized by days 12-15. These findings may provide a first step into defining future biomarkers or correlates of protection after LAIV immunization. PMID- 26148333 TI - Corrigendum. PMID- 26148334 TI - Corrigendum. PMID- 26148335 TI - Survey Instruments for Knowledge, Skills, Attitudes and Behaviour Related to Evidence-based Practice in Occupational Therapy: A Systematic Review. AB - The purpose of this study was to evaluate, through a systematic review, assessment instruments for evidence-based practice (EBP). The specific objectives were to (1) identify survey instruments testing EBP knowledge, skills, attitudes and behaviour; (2) determine the attributes measured by each instrument; (3) evaluate the psychometric properties of the instruments; and (4) evaluate the methodological quality of the instruments. Using the Cochrane approach, searches were conducted in Pubmed, EBSCOHost and Scopus from inception to February 2014. Papers were screened by two independent assessors, and data were extracted by one researcher. Forty papers reporting 34 instruments met the inclusion criteria and were included in the qualitative synthesis. Most instruments measured EBP behaviour (n = 33) and attitudes (n = 21). This review provides a single source of information to enable researchers to select the most robust descriptive instruments to measure EBP learner attributes. Instruments used only with occupational therapists may have resulted in some instruments being missed. For further research, it is recommended that attention is given to developing objective instruments with a focus on knowledge and skills. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26148336 TI - Feasibility of the radioastatination of a monoclonal antibody with astatine-211 purified by wet extraction. AB - Astatine-211, a most promising alpha-particle emitter for targeted radiotherapy, is generally obtained by high-temperature distillation. However, a liquid-liquid extraction procedure (wet extraction) has also been described. The purpose of this study was to develop and optimize the labelling of the stannylated-activated ester N-hydroxysuccinimidyl-meta-trimethylstannylbenzoate ester (MeSTB) with astatine-211 extracted in di-isopropylether (DIPE) in the presence of the oxidant N-chlorosuccinimide (NCS). The effect of final volume, incubation duration and NCS amounts on radiolabelling yield was studied. The best yields (85-90%) of N hydroxysuccinimidyl-meta-[(211)At]astatobenzoate ester (SAB) were obtained with 20 nmol of MeSTB, 100 nmol of NCS in 120 uL of DIPE after 15 min. The astatine 211-labelled-activated ester was then used to radiolabel a monoclonal antibody (mAb). The labelling yield was 20-25% and the radiochemical purity was 97-99%. These results show that mAbs may be efficiently labelled with astatine-211 obtained by wet extraction, a fully automatable technique that may prove to be a useful alternative to dry distillation for high activity labelling of radiopharmaceuticals. Copyright (c) 2008 John Wiley & Sons, Ltd. PMID- 26148337 TI - Thermal niche predicts tolerance to habitat conversion in tropical amphibians and reptiles. AB - Habitat conversion is a major driver of the biodiversity crisis, yet why some species undergo local extinction while others thrive under novel conditions remains unclear. We suggest that focusing on species' niches, rather than traits, may provide the predictive power needed to forecast biodiversity change. We first examine two Neotropical frog congeners with drastically different affinities to deforestation and document how thermal niche explains deforestation tolerance. The more deforestation-tolerant species is associated with warmer macroclimates across Costa Rica, and warmer microclimates within landscapes. Further, in laboratory experiments, the more deforestation-tolerant species has critical thermal limits, and a jumping performance optimum, shifted ~2 degrees C warmer than those of the more forest-affiliated species, corresponding to the ~3 degrees C difference in daytime maximum temperature that these species experience between habitats. Crucially, neither species strictly specializes on either habitat - instead habitat use is governed by regional environmental temperature. Both species track temperature along an elevational gradient, and shift their habitat use from cooler forest at lower elevations to warmer deforested pastures upslope. To generalize these conclusions, we expand our analysis to the entire mid-elevational herpetological community of southern Costa Rica. We assess the climatological affinities of 33 amphibian and reptile species, showing that across both taxonomic classes, thermal niche predicts presence in deforested habitat as well as or better than many commonly used traits. These data suggest that warm-adapted species carry a significant survival advantage amidst the synergistic impacts of land-use conversion and climate change. PMID- 26148339 TI - Effects of moderate- and high-intensity chronic exercise on brain-derived neurotrophic factor expression in fast and slow muscles. AB - INTRODUCTION: Brain-derived neurotrophic factor (BDNF) protein expression is sensitive to cellular activity. In the sedentary state, BDNF expression is affected by the muscle phenotype. METHODS: Eighteen Wistar rats were divided into the following 3 groups: sedentary (S); moderate-intensity training (MIT); and high-intensity training (HIT). The training protocol lasted 8 weeks. Forty-eight hours after training, total RNA and protein levels in the soleus and plantaris muscles were obtained. RESULTS: In the plantaris, the BDNF protein level was lower in the HIT than in the S group (P < 0.05). A similar effect was found in the soleus (without significant difference). In the soleus, higher Bdnf mRNA levels were found in the HIT group (P < 0.001 vs. S and MIT groups). In the plantaris muscle, similar Bdnf mRNA levels were found in all groups. CONCLUSIONS: These results indicate that high-intensity chronic exercise reduces BDNF protein level in fast muscles and increases Bdnf mRNA levels in slow muscles. PMID- 26148338 TI - The Processing of Causal and Hierarchical Relations in Semantic Memory as Revealed by N400 and Frontal Negativity. AB - Most current studies investigating semantic memory have focused on associative (ring-emerald) or taxonomic relations (bird-sparrow). Little is known about the question of how causal relations (virus-epidemic) are stored and accessed in semantic memory. The goal of this study was to examine the processing of causally related, general associatively related and hierarchically related word pairs when participants were required to evaluate whether pairs of words were related in any way. The ERP data showed that the N400 amplitude (200-500 ms) elicited by unrelated related words was more negative than all related words. Furthermore, the late frontal distributed negativity (500-700 ms) elicited by causally related words was smaller than hierarchically related words, but not for general associated words. These results suggested the processing of causal relations and hierarchical relations in semantic memory recruited different degrees of cognitive resources, especially for role binding. PMID- 26148340 TI - Quantitative Comparison of the Effect of 10% Phenylephrine Instillation and Manual Elevation in Patients with Involutional Blepharoptosis. AB - OBJECTIVE: To compare the effect of 10% phenylephrine (PE) instillation and manual elevation (ME) on the upper eyelid position of the tested eye and the contralateral eye in patients with involutional blepharoptosis (IB). METHODS: IB patients were submitted to two tests followed by observation of the effect on the contralateral eyelid: (1) ME of the more ptotic eyelid; and (2) instillation of two drops of 10% PE (phenylephrine test) in the more ptotic eye. The patients were filmed before and 5, 10, and 15 minutes after instillation. The upper eyelid margin reflex distance (MRD1) was measured using the software Image J, and the results were analyzed with the linear mixed-effects model. RESULTS: The study included 70 patients aged 44-86 years, 64 of whom were female (91.43%), divided into three groups: subjects with unilateral IB, subjects with bilateral IB, and controls. The eye submitted to instillation with 10% PE displayed significant elevation during the first 10 min: from 1.33 +/- 0.66 mm to 2.06 +/- 0.89 mm (unilateral group), from 1.26 +/- 0.63 mm to 2.29 +/- 0.86 mm (bilateral group), and from 3.12 +/- 0.68 mm to 4.06 +/- 0.92 mm (control group). MRD1 decreased in the contralateral eye in IB patients, significantly more so after the phenylephrine test: PE vs. ME = 18.9% versus 17.2% reduction in the unilateral group, and 13.6% versus 10.7% reduction in the bilateral group. The outcome was not influenced by IB severity and the concurrence of IB and eye dominance. CONCLUSION: Both ME and 10% PE affected the contralateral upper eyelid, but the response was significantly better with the latter. PMID- 26148341 TI - On interpretation of protein X-ray structures: Planarity of the peptide unit. AB - Pauling's mastery of peptide stereochemistry-based on small molecule crystal structures and the theory of chemical bonding-led to his realization that the peptide unit is planar and then to the Pauling-Corey-Branson model of the alpha helix. Similarly, contemporary protein structure refinement is based on experimentally determined diffraction data together with stereochemical restraints. However, even an X-ray structure at ultra-high resolution is still an under-determined model in which the linkage among refinement parameters is complex. Consequently, restrictions imposed on any given parameter can affect the entire structure. Here, we examine recent studies of high resolution protein X ray structures, where substantial distortions of the peptide plane are found to be commonplace. Planarity is assessed by the omega-angle, a dihedral angle determined by the peptide bond (C-N) and its flanking covalent neighbors; for an ideally planar trans peptide, omega = 180 degrees . By using a freely available refinement package, Phenix [Afonine et al. (2012) Acta Cryst. D, 68:352-367], we demonstrate that tightening default restrictions on the omega-angle can significantly reduce apparent deviations from peptide unit planarity without consequent reduction in reported evaluation metrics (e.g., R-factors). To be clear, our result does not show that substantial non-planarity is absent, only that an equivalent alternative model is possible. Resolving this disparity will ultimately require improved understanding of the deformation energy. Meanwhile, we urge inclusion of omega-angle statistics in new structure reports in order to focus critical attention on the usual practice of assigning default values to omega-angle constraints during structure refinement. PMID- 26148342 TI - Administration of IkappaB-kinase inhibitor PS1145 enhances apoptosis in DMBA induced tumor in male Wistar rats. AB - Nuclear factor kappa-B (NF-kappaB), a key anti-apoptotic factor, plays a critical role in tumor cell growth, metastasis, and angiogenesis. The transcriptional activity of NF-kappaB is normally suppressed in the cytoplasm due to its association with a natural inhibitor molecule IkappaB. Phosphorylation of the IkappaB at Ser 32 and Ser 36 by the IkappaB kinase complex (IKK) marks the degradation of the molecule by 26S proteasome. As NF-kappaB is constitutively activated in most of the tumor cells, inhibition of the activities of IKK may significantly sensitize the tumor cells to apoptosis. In the present study, we investigated the effect of IkappaB kinase-specific blocker PS1145 on DMBA-induced skin tumor of male Wistar rats. We examined the apoptotic effect of PS1145 on DMBA-induced tumor by various histopathological and molecular techniques. Our results demonstrate the significant expression of major pro-apoptotic genes like caspases 2, 3, 8, 9, and p53 in PS1145-treated tumor bearing group at mRNA levels as well as significant (P < 0.05) down regulation in the expression levels of NF kappaB and VEGF, the major pro-inflammatory and pro-angiogenic factors, respectively. The histopathological examination showed that the tumor progression, mitotic, AgNOR, and PCNA indices were significantly reduced in PS1145 treatment groups as compared to PBS control on day 28 of post-treatment. Furthermore, significant increase in TUNEL positive nuclei and observation of peculiar apoptotic nuclei in transmission electron microscopy were seen in PS1145 treatment group. We conclude that intravenous application of PS1145 promotes direct apoptosis in DMBA-induced skin tumor in male Wistar rats by blocking NF kappaB and VEGF activities. PMID- 26148343 TI - Vitamin E reduces adipose tissue fibrosis, inflammation, and oxidative stress and improves metabolic profile in obesity. AB - OBJECTIVE: To test whether enhancing the capability of adipose tissue to store lipids using antioxidant supplementation may prevent the lipotoxic effects and improve the metabolic profile of long-term obesity. METHODS: C57BL/6J mice were randomized into three experimental groups for 28 weeks: control group (n = 10) fed chow diet (10% kcal from fat), obese group (O, n = 12) fed high-fat (HF) diet (45% kcal from fat), and obese group fed HF diet and supplemented twice a week with 150 mg of alpha-tocopherol (vitamin E) by oral gavage (OE, n = 12). RESULTS: HF diet resulted in an obese phenotype with a marked insulin resistance, hypertriglyceridemia, and hepatic steatosis in O mice. Histological analysis of obese visceral adipose tissue (VAT) revealed smaller adipocytes surrounded by a fibrotic extracellular matrix and an increased macrophage infiltration, with the consequent release of proinflammatory cytokines. Vitamin E supplementation decreased oxidative stress and reduced collagen deposition in the VAT of OE mice, allowing a further expansion of the adipocytes and increasing the storage capability. As a result, circulating cytokines were reduced and hepatic steasosis, hypertriglyceridemia, and insulin sensitivity were improved. CONCLUSIONS: Our results suggest that oxidative stress is implicated in extracellular matrix remodeling and may play an important role in metabolic regulation. PMID- 26148344 TI - Nozzleless Fabrication of Oil-Core Biopolymeric Microcapsules by the Interfacial Gelation of Pickering Emulsion Templates. AB - Ionotropic gelation has been an attractive method for the fabrication of biopolymeric oil-core microcapsules due to its safe and mild processing conditions. However, the mandatory use of a nozzle system to form the microcapsules restricts the process scalability and the production of small microcapsules (<100 MUm). We report, for the first time, a nozzleless and surfactant-free approach to fabricate oil-core biopolymeric microcapsules through ionotropic gelation at the interface of an O/W Pickering emulsion. This approach involves the self-assembly of calcium carbonate (CaCO3) nanoparticles at the interface of O/W emulsion droplets followed by the addition of a polyanionic biopolymer into the aqueous phase. Subsequently, CaCO3 nanoparticles are dissolved by pH reduction, thus liberating Ca(2+) ions to cross-link the surrounding polyanionic biopolymer to form a shell that encapsulates the oil droplet. We demonstrate the versatility of this method by fabricating microcapsules from different types of polyanionic biopolymers (i.e., alginate, pectin, and gellan gum) and water-immiscible liquid cores (i.e., palm olein, cyclohexane, dichloromethane, and toluene). In addition, small microcapsules with a mean size smaller than 100 MUm can be produced by selecting the appropriate conventional emulsification methods available to prepare the Pickering emulsion. The simplicity and versatility of this method allows biopolymeric microcapsules to be fabricated with ease by ionotropic gelation for numerous applications. PMID- 26148345 TI - Glypican Is a Modulator of Netrin-Mediated Axon Guidance. AB - Netrin is a key axon guidance cue that orients axon growth during neural circuit formation. However, the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown. Here we demonstrate that in Caenorhabditis elegans, LON-2/glypican, a heparan sulfate proteoglycan, modulates UNC-6/netrin signaling and may do this through interactions with the UNC-40/DCC receptor. We show that developing axons misorient in the absence of LON 2/glypican when the SLT-1/slit guidance pathway is compromised and that LON 2/glypican functions in both the attractive and repulsive UNC-6/netrin pathways. We find that the core LON-2/glypican protein, lacking its heparan sulfate chains, and secreted forms of LON-2/glypican are functional in axon guidance. We also find that LON-2/glypican functions from the epidermal substrate cells to guide axons, and we provide evidence that LON-2/glypican associates with UNC-40/DCC receptor-expressing cells. We propose that LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration. PMID- 26148346 TI - Spleen tyrosine kinase (Syk) inhibitor fostamatinib limits tissue damage and fibrosis in a bleomycin-induced scleroderma mouse model. AB - OBJECTIVES: The pathogenesis of fibrosis in scleroderma (SSc) is unknown. TGF beta and platelet-derived growth factor are important in the development of fibrosis and tyrosine kinases are involved in these pathways. The possible antifibrotic effects of various kinase inhibitors in SSc have been studied before. Spleen tyro-sine kinase (Syk) is a protein tyrosine kinase which activates intracellular signal transduction pathways; and has been claimed to be involved in the pathogenesis of systemic autoimmune diseases. Inhibition of Syk suppresses IgE- and IgG-associated FcR signal activation in various cell types; and suppresses experimental arthritis and skin and kidney disease in lupus-prone mice. We investigated the ability of a small drug, the Syk inhibitor, fostamatinib, to protect mice from bleomycin-induced SSc. METHODS: Four study groups of BALB/c mice were included into this study: control, bleomycin (administered subcutaneously to BALB/c mice for 21 days), bleomycin and fostamatinib (mice fed with chow containing a Syk inhibitor for 21 days), and fostamatinib alone groups. Skin and lung tissue specimens were obtained and evaluated histologically. RESULTS: Treatment with fostamatinib significantly reduced skin thickness and fibrosis. Mice treated with fostamatinib also displayed less fibrosis and inflammation in the lung tissue. Following fostamatinib treatment, Syk, phospho-Syk, and TGF-beta expression decreased in both skin and lung tissues. CONCLUSIONS: The Syk inhibitor fostamatinib prevented bleomycin-induced fibrosis and inflammation in the skin and in the lung. The anti fibrotic effect of fostamatinib is linked to reduced Syk phosphorylation and TGF beta expression. The Syk pathway appears as a potential molecular target for therapeutic intervention in SSc. PMID- 26148347 TI - Relationship of abdominal adiposity and body composition with endothelial dysfunction in patients with rheumatoid arthritis. AB - OBJECTIVES: We aimed to investigate whether the abnormalities in body composition and abdominal fat that occur in rheumatoid arthritis (RA) are associated with the presence of endothelial dysfunction. METHODS: Cross-sectional study that encompassed 197 women (100 RA patients and 97 age-matched controls). Patients and controls were evaluated to establish endothelial function by brachial artery flow mediated dilatation (FMD). Dual-x-ray-absorptiometry-derived body composition and abdominal adiposity by magnetic resonance imaging were assessed. Multiple regression analysis was performed to study the relationship between body composition and endothelial function. RESULTS: FMD was higher in controls compared to RA patients (8.5 [4.5-15.6] % vs. 5.3 [0.0-9.2] %, p=0.00). Appendicular-to-total lean mass ratio (0.42 +/- 0.02 vs. 0.40 +/- 0.03, p=0.00) and appendicular-to-trunk lean mass (0.82 +/- 0.08 vs. 0.78 +/- 0.08, p=0.00) were lower in RA patients. Visceral and subcutaneous abdominal fat tissues did not differ between patients and controls. Body mass index over 30 kg/m2 was common in patients and controls (44 and 32%). High sarcopenia tended to be more elevated in RA after multivariate adjustment (13% vs. 7%, p=0.06). Fat mass index showed a negative association (per standard deviation-SD-), after adjusting for comorbidity, with FMD in controls (beta coef. -0.45[-1.05-0.05], p=0.03) but not in patients. Overfat definition (beta coef. -0.81[-1.73-0.00], p=0.05) and visceral fat (per SD beta coef. -0.60 [-1.18-0.02], p=0.04) were associated with a lower FMD values in controls but not in RA patients. Trend analysis revealed that sarcopenia was related to increased endothelial dysfunction in both patients and controls. CONCLUSIONS: Our findings suggest that fat accumulation is not associated with endothelial dysfunction in RA patients. However, RA patients with sarcopenia are more likely to suffer endothelial dysfunction possibly being at higher cardiovascular risk. PMID- 26148349 TI - Bridging the knowledge gap: from microbiome composition to function. AB - Despite the wealth of metagenomic sequencing data, the functions of most bacterial genes from the mammalian microbiota have remained poorly understood. In their recent study (Yaung et al 2015), Wang, Gerber, and colleagues present a platform which allows functional mining of bacterial genomes for genes that contribute to fitness in vivo and holds great potential for forward engineering microbes with enhanced colonization abilities in the microbiota. PMID- 26148348 TI - T160-phosphorylated CDK2 defines threshold for HGF dependent proliferation in primary hepatocytes. AB - Liver regeneration is a tightly controlled process mainly achieved by proliferation of usually quiescent hepatocytes. The specific molecular mechanisms ensuring cell division only in response to proliferative signals such as hepatocyte growth factor (HGF) are not fully understood. Here, we combined quantitative time-resolved analysis of primary mouse hepatocyte proliferation at the single cell and at the population level with mathematical modeling. We showed that numerous G1/S transition components are activated upon hepatocyte isolation whereas DNA replication only occurs upon additional HGF stimulation. In response to HGF, Cyclin:CDK complex formation was increased, p21 rather than p27 was regulated, and Rb expression was enhanced. Quantification of protein levels at the restriction point showed an excess of CDK2 over CDK4 and limiting amounts of the transcription factor E2F-1. Analysis with our mathematical model revealed that T160 phosphorylation of CDK2 correlated best with growth factor-dependent proliferation, which we validated experimentally on both the population and the single cell level. In conclusion, we identified CDK2 phosphorylation as a gate keeping mechanism to maintain hepatocyte quiescence in the absence of HGF. PMID- 26148350 TI - Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia. AB - High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the physiological manifestations of the disease, especially in response to treatment, has not been investigated in a systematic manner. To this end, we studied a mouse model of diet-induced dyslipidemia and atherosclerosis that was subject to various drug treatments relevant to the disease in question. Both physiological data and gene expression data (from the liver and white adipose) were analyzed and compared. We find that treatments that restore gene expression patterns to their norm are associated with the successful restoration of physiological markers to their baselines. This holds in a tissue-specific manner-treatments that reverse the transcriptomic signatures of the disease in a particular tissue are associated with positive physiological effects in that tissue. Further, treatments that introduce large non-restorative gene expression alterations are associated with unfavorable physiological outcomes. These results provide a sound basis to in silico methods that rely on omic metrics for drug repurposing and drug discovery by searching for compounds that reverse a disease's omic signatures. Moreover, they highlight the need to develop drugs that restore the global cellular state to its healthy norm rather than rectify particular disease phenotypes. PMID- 26148351 TI - Improving microbial fitness in the mammalian gut by in vivo temporal functional metagenomics. AB - Elucidating functions of commensal microbial genes in the mammalian gut is challenging because many commensals are recalcitrant to laboratory cultivation and genetic manipulation. We present Temporal FUnctional Metagenomics sequencing (TFUMseq), a platform to functionally mine bacterial genomes for genes that contribute to fitness of commensal bacteria in vivo. Our approach uses metagenomic DNA to construct large-scale heterologous expression libraries that are tracked over time in vivo by deep sequencing and computational methods. To demonstrate our approach, we built a TFUMseq plasmid library using the gut commensal Bacteroides thetaiotaomicron (Bt) and introduced Escherichia coli carrying this library into germfree mice. Population dynamics of library clones revealed Bt genes conferring significant fitness advantages in E. coli over time, including carbohydrate utilization genes, with a Bt galactokinase central to early colonization, and subsequent dominance by a Bt glycoside hydrolase enabling sucrose metabolism coupled with co-evolution of the plasmid library and E. coli genome driving increased galactose utilization. Our findings highlight the utility of functional metagenomics for engineering commensal bacteria with improved properties, including expanded colonization capabilities in vivo. PMID- 26148353 TI - [SPECIFICS OF INHALED ILOPROST PHARMACODYNAMICS IN PATIENTS WITH SEVERE LEFT VENTRICULAR SYSTOLIC DYSFUNCTION]. AB - PURPOSE: To determine the specifics of inhaled iloprost effect on pulmonary and systemic hemodynamics in patients with pulmonary hypertension (PH) associated with left ventricular systolic dysfunction. MATERIALS AND METHODS: 47 vasore- activity tests (VRT) with 20 micrograms inhaled iloprost (Ventavis, Bayer) were performed in 39 candidates on heart transplantation. All patients had heart failure III-IV NYHA and PH with pulmonary vascular resistance (PVR) more than 2.5 Wood units. Hemodynamic parameters were evaluated at baseline and 15 minutes after inhalation of iloprost. RESULTS: Iloprost significant decreased PAPmean: from 36.8 +/- 8.5 mm Hg to 29.9 +/- 9.4 mm Hg (p < 0.001). There was a significant decrease in PVR:from 4.5 1.6 Wood units to 3 +/- 1 Wood units (p < 0.001). PVR dropped more than 20% in 34 cases (72.3%). Iloprost inhalation caused significant changes in systemic hemodynamic. There were decrease in sys- temic vascular resistance (SVR)from 1820 +/- 527 dynes.sec.cm(-5) to 1423 +/- 427 dynes.sec.cm(-5) (p < 0.001), increase in stroke volume index (SVI) from 26.1 +/- 8.7 ml/m2 to 30.5 +/- 9.5 ml/m2 (p < 0.001) and decrease in PCWP from 20.6 +/- 5.9 mm Hg to 18.4 +/- 6.6 mm Hg. (p = 0.016). We found significant negative correlation between systemic effects of iloprost and initial cardiac index (r = 0.63). CONCLUSIONS: Inhaled iloprost caused significant changes in systemic hemodynamic when was used in patients with severe LV systolic dysfunction. Favorable changes in the left ventricle preload and after- load naturally increased its performance and decreased PCWP. PMID- 26148352 TI - Cell shape and the microenvironment regulate nuclear translocation of NF-kappaB in breast epithelial and tumor cells. AB - Although a great deal is known about the signaling events that promote nuclear translocation of NF-kappaB, how cellular biophysics and the microenvironment might regulate the dynamics of this pathway is poorly understood. In this study, we used high-content image analysis and Bayesian network modeling to ask whether cell shape and context features influence NF-kappaB activation using the inherent variability present in unperturbed populations of breast tumor and non-tumor cell lines. Cell-cell contact, cell and nuclear area, and protrusiveness all contributed to variability in NF-kappaB localization in the absence and presence of TNFalpha. Higher levels of nuclear NF-kappaB were associated with mesenchymal like versus epithelial-like morphologies, and RhoA-ROCK-myosin II signaling was critical for mediating shape-based differences in NF-kappaB localization and oscillations. Thus, mechanical factors such as cell shape and the microenvironment can influence NF-kappaB signaling and may in part explain how different phenotypic outcomes can arise from the same chemical cues. PMID- 26148354 TI - [ASSESSMENT OF EXTRAVASCULAR LUNG WATER BY QUANTITATIVE COMPUTER IMAGE ANALYSIS IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME]. AB - PURPOSE: To evaluate the possibility of quantitative computed tomography (CT) of the lungs in patients with acute respiratory distress syndrome (ARDS) for assessment of the severity of the condition and the effectiveness of treatment. MATERIALS AND METHODS: The study included 29 patients with ARDS and 22 with no signs of lung disease (control group). We measured extravascular lung water (EVLW) by transpulmonary thermodilution (TTD) and analysed CT of the lungs in patients with ARDS. Patients in the control group underwent CT of the lungs only. CT images were processed using the "Gamma Multivoks". RESULTS: According to CT poorly ventilated lung areas accounted for 2% of the total in the control group. Normally ventilated and hyper-ventilated lung areas prevailed in these patients. In the group of ARDS hyper-ventilated areas almost were not identified and normality and poorly ventilated areas we found. In patients with ARDS total lung volume was 1.5 times less than in the control group (median volume of 3393 and 4955 mL respectively). Pulmonary weight in ARDS group was bigger than in controls (median weight of the lungs 1233 and 812 g respectively). Effects of treatment according to quantitative CT evaluated in 14 survived patients. Notes the increase in lung volume (median 4656.5 ml) (p = 0.0001) and a decrease in lung weight (median 862 g) (p = 0.0012). The weight and volume of the lungs, the ratio of hyper, normal and poorly ventilated areas of the lung in patients with acute respiratoy distress syndrome after treatment did not differ from those in the control group. CONCLUSIONS: Quantitative analysis of CT reveals changes in the mass and volume of the lungs and can be used to diagnose and evaluate the effectiveness of the treatment. Pulmonary weight calculated by CT correlates with EVLW determined by TTD. PMID- 26148355 TI - [PHARMACOLOGICAL CARDIOPROTECTION DURING REPERFUSION OF ISOLATED HEART]. AB - PURPOSE: To study the contractile function, the degree of damage and regional myocardial metabolism in the isolated rat heart model subjected to cardioplegic stop and reperfusion under the protection of levosimendan. MATERIALS AND METHODS: The study was performed on isolated rat hearts Wistar (group using "Custodiol" vs group using "Custodiol" + "Levosimendan". We assessed the extent of myocardial damage (in terms of markers of myocardial necrosis), the contractile function of the myocardium (coronary flow, heart rate, left ventricular pressure), the dynamics of redox processes during reperfusion with a parallel study of histology of the myocardium. RESULTS: We found a presence of cardioprotective effect of levosimendan in respect of the isolated heart in the reperfusion period of cardioplegic ischemia. The effect related to reducing the emission of reperfusion enzyme markers of myocardial damage, reducing the severity of pathological changes in the myocardium and reducing the intensity of free radical reactions in the myocardium. CONCLUSIONS: Cardioprotection with levosimendan reduces the severity of free radical attack the isolated heart, reduces the severity of damage to cardiomyocytes and preserves the contractile activity of the myocardium during reperfusion due to the effect of postconditioning. PMID- 26148356 TI - [CRITERIA OF HIGH RISK INFECTION PULMONARY COMPLICATIONS IN SEVERE POLYTRAUMA PATIENTS]. AB - PURPOSE: To identify high risk groups for infectious pulmonary complications (IPC) in patients with severe polytrauma, depending on the severity of the damage and the volume of acute blood loss in intensive care units in the early stages of the injury. MATERIAL AND METHODS: We studied 410 patients with severe polytrauma and IPC. Severity of injury was calculated according to ISS scale. ROC-curve was made in order to assess the prognostic significance of the impact of the severity of injury and the volume of acute blood loss on the development of IPC. RESULTS: To evaluate the effect of injury severity on the incidence of IPC, patients were divided into 2 groups: I--185 (ISS < 30) and group II--225 (ISS >= 30). In group I, prolonged mechanical ventilation was required in 4 patients (2.2%), pneumonia occurred in 9 patients (4.9%), no one died In group II--prolonged mechanical ventilation was performed in 120 (47.6%), pneumonia occurred in 158 (70.2%), sepsis--in 14 (6.2%), 37 (16.4%) patients died. Depending on the volume of blood loss into two groups: I group--179 patients (blood loss < 2000 ml) and group II- 231 (blood loss >= 2000 ml). Prolonged mechanical ventilation was required 14 (7.6%) patients in group I and at 110 (47.6%)--II group, pneumonia developed in 14 (7.6%) and 153 (66.2%), respectively. Sepsis was developed in 14 patients of group II, whereas in patients of group I it was not registered also differed the number of deaths in the early period: in group 14 (2.2%) patients died, in II--33 (14.3%). CONCLUSIONS: Comparative statistical analysis revealed important criteriafor the prognosis of the IPC in patients with severe polytrauma: the severity of damage on a ISS >= 30 points and the volume of acute blood loss >= 2000 ml. PMID- 26148357 TI - [THE ROLE OF MICROBIOLOGICAL MONITORING AND DRUG HISTORY IN THE EFFECTIVENESS OF ANTIBIOTIC PROPHYLAXIS AND ANTIBIOTIC TREATMENT OF INFECTIOUS COMPLICATIONS AFTER RECONSTRUCTIVE SURGERIES]. AB - MATERIAL AND METHODS: We analyzed the results of the local microbiological monitoring carried out in 2010-2013. The monitoring included the study of biological material of patients with clinical signs of infectious and inflammatory complications after reconstructive surgery. We studied the dynamics of the isolation of major pathogens (Staphylococcus spp., Enterococcus spp., representatives of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Candida spp.) and their sensitivity to major antibiotics. RESULTS: We demonstrated the role of local monitoring and knowledge of the "drug history" in achieving of effective starting empirical antibiotic therapy. PMID- 26148358 TI - [RUSSIAN NATIONAL EPIDEMIOLOGICAL STUDY "RUVENT": THE USE OF ARTIFICIAL LUNG VENTILATION IN THE INTENSIVE THERAPY IN CHILDREN]. AB - Purpose of this part of the "RuVent" research is to study the real use of the various modes and parameters of prolonged respiratory support in children in Russia. MATERIALS AND METHODS: The study included 104 children from 29 ICUs (28 in Russian Federation, 1 in Ukraine) under the age of 15 years with ALV duration more than 12 hours in the period from February 7 to 11, 2011. The collection of information performed through online forms. RESULTS: Total lethality was 20.7% (18 of 87 patients). The main reasons for prolonged respiratory support in children were the pathology of the respiratory system: acute respiratory distress syndrome (21.2%), community-acquired pneumonia (9.5%), sepsis (8.2%), and congenital disorders of the central nervous system (8.2%) and cardiac arrest (8.2%). According to the study "RuVent" doctors mostly prefer managed modes of respiratory support (SIMV 41.3%, A/C 28.8%, BIPAP 12.5%). Frequency of non invasive respiratory support use amounted to 1%. Real respiratory volume based on ideal body weight calculation, averaged for boys 9.2 (7.3; 11.2) ml/kg (n = 54), for girls--8.7 (7.1; 10.1) m/kg (n = 38). PEEP median amounted to 4 mbar Tracheostomy was performed in 12 children out of 104 (11.5%), predominantly classic (n = 11), puncture dilated tracheostomy was performed in 1 child. The median of the tracheostomy installation in children was 24.5 days. The duration of respiratory support in children was 11 days (5; 25) (n = 43). The incidence of ventilator-associated pneumonia in children was 27.9% (12 of 43 cases). CONCLUSIONS: The results of the Russian national epidemiological study of the use of mechanical ventilation in the Intensive care unit ("RuVent") showed comparable data with real international clinical practice. The researchers noted significant differences during prolonged mechanical ventilation in children compared with adult patients. PMID- 26148359 TI - [PREVENTION OF VENTILATOR ASSOCIATED INFECTION IN NEONATES WITH RESPIRATORY DISTRESS SYNDROME]. AB - The aim of the research was to reduce the risk ventilator-associated infections (VAI) in neonates with respiratory distress syndrome. DESIGN: retrospective, observational, single center, historical control. MATERIALS AND METHODS: 113 newborns were included in the study. Ventilator-associated pneumonia was diagnosed based on the criteria of VAP CDC/NNIS. Ventilator-associated tracheobronchitis was determined on the basis of criteria of Code LRI-BRON proposed CDC National Healthcare Safety Network. Patients divided into two groups. In the main group (n=54) hand hygiene, closed suction system and non invasive mechanical ventilation were used as a methods of prevention of ventilator-associated infection (IAI). In comparison group (n = 59) hand hygiene only. RESULTS: The frequency of VAI was 27.5 per 1000 days of ventilation. Timing of development and the etiology of VAI were comparable in both groups of patients the duration of mechanical ventilation was significantly (p = 0.01) lower in the main group. In the main group length of stay in the intensive care unit (p = 0.01) and duration of hospital treatment (p = 0.047) decreased The incidence of VAI was significantly lower in the main group (p < 0.05). CONCLUSIONS: Closed suction system with hand hygiene and early weaning from the respirator are acceptable methods of prevention of lower respiratory tract infection associated with mechanical ventilation in neonates with respiratorv distress syndrome. PMID- 26148360 TI - [AIRWAY MANAGEMENT IN CHILDREN DURING RESECTION OF THE TONSILS]. AB - MATERIALS AND METHODS: We conducted a comparative evaluation of anesthesia used during tracheal intubation with and without the application of muscle relaxants in cases of adenotonsillectomy in children. Intubation parameters were evaluated according to Cormack-Lehane scale; the presence of cough reflex, limb movement, laryngospasm and desaturation during intubation was also taken into account. The presence of cough, husky voice, and complaints of pain in the throat were recorded in the monitoring report after extubation. We used the MOPS scale to evaluate postoperative pain and discomfort in children. RESULTS: Tracheal intubation in children with adenotonsillectomy without the use of muscle relaxants was successfid in 100% of the cases, despite the fact that, according to the Cormack-Lehane classification, first degree of visualisation of the glottis during direct laryngoscopy was observed in 79.3% of the cases and the second degree was observed in 20.7% of the cases. No significant reactions in the cardiovascular system to the endotracheal tube were noted. The group without the use of muscle relaxants (p < 0.05) experienced earlier extubation and a shorter duration of anesthesia, which in turn contributed to a more rapid activation of the patients. According to the number of post-intubation complications, no significant differences in the two groups were observed. According to the MOPS scale, higher scores (p < 0.05), indicating discomfort in the early postoperative (within the first 15 minutes after the operation) period were observed in the group with the use of muscle relaxants. CONCLUSIONS: Thus, the method of tracheal intubation without the use of muscle relaxants can be used for adenotonsillectomy in children. PMID- 26148361 TI - [EFFECT OF NEONATAL RESPIRATORY SUPPORT STRATEGIES IN THE ICU]. AB - This review deals with the current trends in protective ventilation in newborns. Volumotrauma is the most common variant of ventilator-induced lung injury. The modern research is devoted to the study of biotrauma, which is the release of inflammatory mediators in response to mechanical ventilation. There is a correlation between the ventilator-induced lung injury and the development of chronic lung diseases in infants. Now we have the "new" form of bronchopulmonary dysplasia-parenchymal lung disease characterized by impaired growth and development of the alveoli and blood vessels of the pulmonary circulation. Some authors believe that the use of noninvasive ventilation as a starting method of respiratory support reduce the risk of bronchopulmonary dysplasia. The modern protective ventilation involves two main principles to reduce ventilator-induced lung injury: a decrease in tidal volume (V) and the principle of permissive hypercapnia. Application ofthe method of permissive hypercapnia and modes of the target volume can reduce the likelihood of ventilator-induced lung injury in newborn infants. Despite the limitation of the indications for mechanical ventilation in modern neonatology and widespread use of noninvasive ventilation for patients who really need mechanical ventilation, the use of modes with the target volume provides the best chance to reduce the complications of ventilation. PMID- 26148362 TI - [INDUCTION OF ANESTHESIA ON THE BASIS OF DESFLURANE AND FENTANYL--DANGER IN THE AMBULATORY SURGERY]. AB - PURPOSE: To study the possibility of desflurane use for induction of anesthesia. MATERIALS AND METHODS: We analysed the intra- and immediate postoperative periods in 125 patients. Depending on the intended anesthesia method patients were randomised (the method of the envelopes) and included in one of two study groups: 1--volatile desflurane-based anesthesia (n = 62); 2--volatile sevoflurane-based anesthesia (n = 63). RESULTS: Desflurane based anesthesia led to apnea until the installation of laryngeal mask in 94.5% of patients (of 54), for whom a completion of inhalation induction was possible, whereas sevoflurane based anesthesia.led to apnea occurred only in one patient (1.6%). CONCLUSIONS: "Step up" desflurane-based inhalational induction and sevoflurane-based maximum concentration inhalational induction "without primaryfilling of the circuit" showed no significant in time necessary for achieving an anesthetic concentration essential for LMA installation. In both groups it was 3-5 min. desflurane-based volatile induction with addition of fentanyl led to apnea in 97% of patients and associates with a higher risk of bronchospasm. PMID- 26148363 TI - [PAIN AFTER CHILDBIRTH AND ITS IMPACT ON QUALITY OF LIFE]. AB - BACKGROUND: Public attitude towards labor pain and pain relief in labor is not fully formed. PURPOSE: To study the frequency of formation of acute and chronic pain during delivery. MATERIALS AND METHODS: Retrospectively we surveyed 300 women 18-48 years old, who had childbirth naturally or by caesarean section for 4 6 months before the survey and analyzed the history of their childbirth. RESULTS: The obtained data showed that the problem with generic pain has real medical and social consequences, significantly altering the quality of life of women as during childbirth and the postpartum period. Of those surveyed, 74.9% of women in childbirth experienced severe pain during labor; which had 16.7% of women had led to a complete loss of mobility. With approximately 20% of women believed the use of methods of anaesthesia was dangerous and 63% thought that anaesthesia is possible only under strict obstetric indications. Only 20% of pregnant women expected to give birth without pain. In 3-6 months. after labor representation mothers opinion was not changed significantly. In 1 month or more after delivery or cesarean section pain was presented in 21% of women, in 2-3 months--13.7%, in more than 3 months--7%. In 4.3% of the patients the pain persistedfor 5-6 months. CONCLUSIONS: Significant relationship between persistent for a long time after childbirth pain and the way the urgency of delivery, the method of anesthesia for caesarean section, the expression of acute pain during childbirth was not revealed. PMID- 26148364 TI - [COMPARISON OF THE EFFECTIVENESS OF ILIOINGUINAL-ILIOHYPOGASTRIC BLOCKADE AND TRANSVERSUS ABDOMINIS PLANE BLOCK FOR ANALGESIA AFTER CESAREAN SECTION]. AB - In this prospective randomized study we compared the analgesic efficacy of the ilioinguinal-iliohypogastric nerves block and transversus abdominis plane block for analgesia after caesarean delivery performed by suprapubic laparotomy. The study includes 164 healthy women with ASA status I-II class, undergoing elective surgery under spinal anaesthesia. During the first postoperative hour patients in the "block's" groups received ultrasound-guided blocks of the anterior abdominal wall with ropivacaine 100 mg both. For the TAP-block we used 20 ml 0.25% solution, for the ilioinguinal-iliohypogastric block--10 ml 0.5% from each side. Patients were monitored for visual analogue scale (VAS) scores at rest and during movement (at 3, 6, 9, 12 and 24 hours after surgery), concentration of the cortisol and glucose were measured, and consumption of the tramadol and its adverse effects were controlled. We concluded that both blocks improve postoperative analgesia after caesarean delivery. The Ilioinguinal iliohypogastric block showed greater efficacy than the transversus abdominis plane block. PMID- 26148365 TI - [NONSPECIFIC DELIRIUM IN THE INTENSIVE CARE UNIT]. AB - Delirium in the intensive care unit is a frequent and serious complication, significantly worsens the prognosis of the underlying disease. Diagnoses that assign patients with delirium include an acute encephalopathy toxic encephalopathy, resuscitation psychosis, and this is an incomplete list. Thus, delirium is apparently not a separate disease, is more likely that this is a symptom of central nervous system polyethiological inherently. Currently only two methods for the diagnosis of delirium are recommended: the assessment of confusion for the ICU (CAM-ICU) and a checklist for the assessment of delirium in the ICU (ICDSC). There are no specific methods for the prevention of delirium, but the observance of some simple rules can prevent its development. We should treat the disease, which has led to the appearance of delirium symptoms. For relief discussed the state recommended that a mild sedative non-benzodiazepine drugs (dexmedetomidine better) with a daily assessment of the level of consciousness. PMID- 26148366 TI - [OLD AND NEW PROBLEMS IN THE TRAINING OF ANAESTHESIOLOGISTS]. AB - In connection with the upcoming changes in the professional education in Russia, there is a need to adapt the existing system of training of anesthesiologists. We sent questionnaires to 831 anesthesiologists to identify their opinion about the planned transition to continuous medical education. We found that the majority of respondents do not object to the implementation in practice of this system, especially if the educational model will be adapted to the specific requests of practitioners. Reorganization of the system of higher and additional professional education requires state educational and medical institutions, and public organizations of the effective interaction. Public professional organizations should play the more active role of facilitators of the educational process. PMID- 26148367 TI - [MODERN TECHNOLOGIES FOR MONITORING AND CORRECTION OF BLOOD GLUCOSE LEVELS IN PATIENTS IN THE INTENSIVE CARE UNIT]. AB - Currently, new technologies of timely diagnosis and correction of disorders of carbohydrate metabolism are constantly introducing in intensive care units. The technologies aimed to improve the safety of the patient during intensive care. These methods include continuous monitoring (subcutaneous, intravascular) and the control of blood glucose levels, based on technologies such as enzymatic and electrochemical, fluorescence, infrared and others. Computer technologies proposed an algorithm of glycemic control with mathematical models occupy an important place. One of such algorithms is eMPC, which predicts blood glucose levels and offers physician a choice of a rate of intravenous administration of insulin and the time of further control of the glucose level. Researchers have demonstrated promising results of such technologies in patients in the ICU. Systems of continuous glucose monitoring can improve the safety of patients suffering from diabetes, as well as during intravenous insulin therapy and artifcial feeding. PMID- 26148368 TI - [DEXMEDETOMIDINE--THEORY OR EXPERIENCE?]. AB - So far, the ongoing debate about the appropriateness of combining drugs with different mechanisms of analgesic action for optimal antinociceptive protection. The review deals with the theoretical calculations arguing with the physiological rationality for the inclusion of central alpha2-agonists in the scheme of modern multimodal analgesia. We have presented data from recent reviews regarding the efficacy and safety of intraoperative application of dexmedetomidine as a one of the latest drugs in this class. PMID- 26148369 TI - [EMERGENCY TREATMENT OF BLEEDING IN PATIENTS TAKING WARFARIN]. AB - Anticoagulant therapy with vitamin K antagonists (AVK) is an effective treatment and prevention of thrombosis. One of the major disadvantages of the AVK is a risk for serious bleeding. Prothrombin complex concentrates (PCC), fresh frozen plasma (FFP) and vitamin K1 are available for control of these situations. The experience of special team ofthe Scientific Center for Hematology was the basis for presented retrospective study. Three regimens of warfarin-related bleeding were compared: PCC+ VK for several bleeding, FFP+ VK for different clinical situations and VKfor light bleeding. PCC showed himself as effective and safe hemostatic agent. Transfusions of FFP were sometimes not effective, sometimes led to TACO. Supplementation of vitamin K1 for patients of I and II groups provided more stable control of hemostasis. In III group VK vas effective to stop bleeding. Two impotent sings for conclusion: necessary of laboratory monitoring, TEG first of all; individual balance of hemostasis base of bleeding or thrombotic risks. PMID- 26148370 TI - [PERIOPERATIVE CARE FOR PATIENTS WITH UNDERLYING ARTERIAL HYPERTENSION (CLINICAL GUIDELINES)]. AB - These clinical guidelines apply to the implementation of health care for all patients with concomitant hypertension in the perioperative period in a hospital. The guidelines specify the method of stratifying the risk of perioperative cardiac complications. We described methods for the treatment of urgent conditions with hypertension and hypertensive crises and identified the main features of the preoperative evaluation and preparation of patients with concomitant hypertension. The clinical guidelines contain recommendations on the management of intra- and postoperative period PMID- 26148371 TI - Heart transplantation in patients with previous malignancy. An overview. AB - INTRODUCTION: A history of malignancy has been considered as a contraindication for heart transplantation. The number of patients with prior malignancy needing transplantation is increasing due to improved survival and to cardiotoxic cancer treatment. However, this reluctance for transplantation can be challenged by the already available results. METHODS: A systematic literature search was performed in electronic databases. After exclusion of cardiac sarcomas, three case reports, thirteen series of which three are paediatric, two database searches and one article with specific design have been found. The larger series are of more recent origin. The study design of the manuscripts differed to some degree. RESULTS: The preoperative profile and the postoperative results are reviewed. The preoperative profile includes demographics, interval between treatment of malignancy and transplantation, indication of transplantation and differences between patients with and without prior malignancy. An important observation is the increase of transplantation in patients with chemotherapy-related cardiomyopathy over time. The postoperative results.show that hospital mortality and long-term survival do not differ significantly between patients with and without pre-transplant malignancy. This seems also to be true for post-transplant recurrence.The disease-free pre-transplant interval has a major effect on both outcomes. Patients with haematologic malignancies and after splenectomy have a worse prognosis. Use of LVAD (left ventricular assist device) as bridge-to transplant and rapamycin as immune suppression, holds some promises. CONCLUSIONS: This review has some limitations since the published series are not comparable. It seems that transplantation in patients with prior malignancy can be justified in some cases, especially when the interval between malignancy and transplantation exceeds five years. PMID- 26148372 TI - Percutaneous closure of inter-atrial communications (atrial septal defect and patent foramen ovale): single-centre experience and mid-term follow-up. AB - BACKGROUND: Percutaneous closure of atrial septal defect (ASD) and patent foramen ovale (PFO) are increasingly being performed. Effective closure rate depends on the anatomy of the interatrial septum and the device used, but its relationship with outcome is poorly described. This study aimed at evaluating: (1) effective ASD and PFO closure rate, (2) factors related with effective closure rate, and (3) factors related with mid-term outcome. METHODS: All patients who underwent percutaneous ASD or PFO closure at Jessa Hospital Hasselt between April 2002 and February 2014 were enrolled. Closure rate was evaluated using consecutive contrast echocardiography studies. Adverse events were defined as a composite of all-cause mortality, hospitalization for heart failure, atrial arrhythmias and thrombo-embolic event. RESULTS: One-hundred and two patients (52 +/- 12 y, 42% male, 75 PFO and 27 ASD) were included in the study. Moderate residual shunt was present in 6% and 10% 6 years after ASD and PFO closure, respectively. The presence of an aneurysmatic interatrial septum was associated with residual shunt after PFO closure (HR 0.57 95% CI 0.33-0.96; P=0.031). Pulmonary hypertension (HR 1.09 95% CI 1.01-1.17; P=0.017) and a history of atrial arrhythmias in ASD (HR 4.28 95% CI 1.06-17.40; P=0.046) and age at closure (HR 1.09 95% CI 1.02-1.16; P=0.012) in PFO patients were related with adverse events. The highest rate of adverse events was observed after placement of a Helex Septal Occluder. Amplatzer and Occlutech devices yielded higher effective closure rates. CONCLUSIONS: Effective closure rates were acceptable 6 years after ASD and PFO closure. The presence of an aneurysmatic septum is associated with residual shunting after PFO closure. Pulmonary hypertension in ASD and older age at closure in PFO are associated with adverse outcome. Adverse events are more frequent with the Helex occluder and effective closure rate depends on the device used. PMID- 26148373 TI - Participation in cardiac rehabilitation after hospitalisation for heart failure: a report from the BIO-HF registry. AB - OBJECTIVE: Participation in cardiac rehabilitation (CR) after hospitalisation for heart failure (HF) is estimated to below, but specific data for Belgium are lacking. Therefore, we wanted to evaluate attendance after HF hospitalisation compared to patients after cardiac surgery or acute coronary syndrome (ACS). Moreover, the improvement in exercise capacity was compared with the other patient groups. METHODS AND RESULTS: Patients who were hospitalized for HF (n=428), cardiac surgery (n=358) or ACS (n=467) in a single hospital, were prospectively included between January 2010 and May 2012. After hospitalisation for HF only 9% participated, compared to 29% after ACS and 56% after cardiac surgery. Non-participants in HF were older, more frequently women (P <0.01) and had a better left ventricular ejection fraction (P < 0.05). In addition, they had more frequently atrial fibrillation and problems to walk independently (P <0.01). At the start of the CR, HF patients had a worse clinical status and exercise capacity than patients after cardiac surgery or ACS (all P <0.001). However, exercise training resulted in a significant improvement in each group separately (all P < 0.001) and the relative improvement in exercise capacity in HF was comparable with the other groups. CONCLUSIONS: Only 9% of HF patients participated in CR after hospitalisation. Age, female gender, a relatively well preserved ventricular function and atrial fibrillation seem to impede attendance to CR. However, HF patients can have as much improvement in exercise capacity as other patient populations, suggesting that more effort is needed to increase participation in CR among HF patients. PMID- 26148374 TI - Metabolic syndrome: influence on clinical severity and prognosis in patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. AB - OBJECTIVE: The aim of this study was to investigate the metabolic syndrome (MS) influence on clinical severity and prognosis in patients with acute ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS: We prospectively analysed 250 patients with acute STEMI treated with primary PCI, between September 2011-2012. MS was diagnosed by the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Patients were divided into two groups (with/without MS) and compared by their baseline data (medical history, demographic and anthropometric data) and parameters of severity (clinical, laboratory, echocardiography, coronary angiography and in-hospital complications data) and prognosis (major adverse cardiovascular events and sick leave duration (SLD) during 12 months offollow-up). Results Our study included 136 (54.4%) and 114 (45.6%) patients with and without MS, respectively. MS patients had longer hospitalization (9.0 vs 8.0 days), higher rates of total in-hospital complications (25.0% vs 14.9%), higher number of significantly stenosed coronary arteries (CAs) (2 vs 1), higher stent diameters (3.5 vs 3.0 mm), higher rate of significantly stenosed proximal and middle CAs segments (94.1% vs 86.7%), and longer SLD (16 vs 10 weeks) (P < 0.05). MS was independently associated with higher risk of total in-hospital complications (odds ratio (OR) 1.90, confidence interval (CI) [1.06-3.64], P = 0.047) and with higher risk of > or =2 significant stenosed CAs (OR 1.72, Cl [1.04-2.84], P= 0.034). CONCLUSION: MS in acute STEMI is an important predictor of total in-hospital complications and severity of CAs disease, but not for other parameters of severity and prognosis. MS patients have longer SLD. PMID- 26148375 TI - Ranolazine enhances nicardipine-induced relaxation of alpha1-adrenoceptor mediated contraction on isolated rabbit aorta. AB - Ranolazine (RAN) and nicardipine (NIC) have been studied for their vasorelaxing effects but the combination of these agents against adrenergic vasoconstriction has not been tested. The present study aimed at investigating the vasorelaxing effect by the combination of the two agents on alpha1-adrenoceptor-mediated contraction on isolated rabbit aorta. Aortic rings were mounted for isometric tension recording in organ baths containing Krebs-Henseleit solution. Concentration-response curves of RAN (10(-9) to 10(-4) M), NIC (10(-1) to 10(-5) M), and RAN + NIC (3 x 10(-6) M) were obtained in a cumulative manner using phenylephrine (PE, 2 x 10(-6) M) as constrictor agent. The effective concentration (EC)50 values for RAN and NIC were 6.5 x 10(-6) M and 1.4 x 10(-5) M, respectively. The treatment of PE-precontracted aortic rings with either RAN or NIC up to 65 min revealed that both agents displayed a biphasic pattern of initial rising and late sustained phases of relaxation. At 35 min of incubation, RAN and NIC induced relaxation by 23 +/- 3% and 14 +/- 4%, respectively (N = 7, P=NS, RAN vs. NIC); their combination resulted in a 34 +/- 4% relaxation (N=7; P < 0.01, RAN + NIC vs. NIC). At 65 min the effect of NIC prevailed and tended to be closer to the values of the combination treatment (P < 0.01, RAN + NIC vs. RAN). The results indicate that RAN at therapeutic concentrations exerts a significant additive vasorelaxing effect when combined with NIC in rabbit aorta. PMID- 26148376 TI - An interactive web-based module to teach physician assistants about venous thromboembolism. AB - OBJECTIVE: Questions about venous thromboembolism (VTE) management result in a high number of cardiovascular consults at one large teaching hospital. However, many of these consults are deemed "inappropriate" by the receiving consultants. This combination presented an opportunity to examine the efficacy of interprofessional education through an interactive web-based module to teach physician assistants (PAs) about VTE management. METHODS AND RESULTS: A web-based module and survey with interactive cases encompassing key VTE management decisions was distributed to 41 inpatient oncology PAs. Usability, satisfaction, and efficacy were evaluated using knowledge and Likert-scale items. Participating PAs improved their VTE knowledge with a pre-module assessment score of 31.7% correct and post-module score of 63.3% (P = 0.0016).There was an increase in self reported comfort for managing VTE (mean 3.92 vs. 3.07; P= 0.004) and calling cardiovascular consults (4.08 vs. 2.50; P < 0.0001). The PAs would highly recommend the module and use it in their practice with 76.9% of them ranking it as their most preferred learning method. CONCLUSION: A brief, interactive web based module increased knowledge and comfort level with VTE management among PAs. This module design can serve as a template for a wide range of cardiovascular learning tools. PMID- 26148377 TI - Systemic lupus erythematosus: the influence of disease-related and classical risk factors on intima media thickness and prevalence of atherosclerotic plaques--a preliminary report. Beneficial effect of immunosuppressive treatment on carotid intima media thickness. AB - OBJECTIVE: The risk of cardiovascular disease is increased in systemic lupus erythematosus (SLE). A meta-analysis showed increased carotid intima media thickness (IMT) in SLE. The aim of this study was to assess the influence of different SLE characteristics and treatment regimens on IMT and atherosclerotic plaques. METHODS AND RESULTS: One hundred and three SLE patients and 95 age- and sex-matched control subjects were included in the study. MT was measured in the common carotid arteries bilaterally. Common carotid arteries, internal carotid arteries and superficial femoral arteries were also screened for the presence of plaques. The presence of plaques was correlated with age (P = 0.00002), male sex (P = 0.034), Framingham 10-year risk score (P < 1 x 10(-6)), SLE duration (P = 0.00006), lack of immunologic disorder (P = 0.0014) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (P = 0.049). IMT was associated with SLE duration (P = 0.002), body mass index (P = 0.026), Framingham 10-year risk score (P < 0.001), total cholesterol concentration (P = 0.002), LDL cholesterol concentration (P = 0.007), SLICC/ACR (P = 0.035), hypertension (P = 0.002), immunologic disorder (P = 0.00008) and discontinuous treatment with immunosuppressive drugs (P = 0.043). CONCLUSIONS: We found a correlation between atherosclerosis and several classical cardiovascular risk factors and disease-related factors. A beneficial effect of continuous immunosuppressive treatment on IMT suggests that appropriate disease control with steroid-sparing agents may protect against atherosclerosis in SLE patients. PMID- 26148378 TI - Prothrombin 3'end gene variants in isolated pulmonary embolism--the first report of FIIc.*64_*66del and FIIc.*303T>C variants. AB - OBJECTIVE: Pulmonary embolism is usually considered as a complication of deep vein thrombosis, but there are still a number of cases of isolated pulmonary embolism. We aimed to investigate whether prothrombin 3'end gene variants might play a significant role in the pathogenesis of isolated pulmonary embolism. METHODS AND RESULTS: In this study 100 patients with isolated pulmonary embolism and 100 controls were screened by DNA sequencing. Screening included last intron, last exon, 3'UTR and part of the 3'FR region of the prothrombin gene. Our results have shown that heterozygous carriers of the FIi G2021 OA variant have a significantly higher risk of isolated pulmonary embolism (OR 4.83; 95% CI 1.33 17.52; P=0.02). Carriers of the Ili 19911GG genotype (OR 1.41; 95% CI 0.72-2.73; P=0.31) and FII 20068CT genotype (OR 3.06; 95% CI 0.31-29.95; P=0.34) were more frequent in patients with isolated pulmonary embolism compared to controls. We also detected the novel gene variants, FIIc.*64_*66del and FII c.*303T>C, in two patients. CONCLUSIONS: Our results suggest that FII G20210A represents a significant risk factor for isolated pulmonary embolism. The FII G19911A and FII C20068T are potentially associated with an increased risk for the occurrence of isolated pulmonary embolism, but the results did not reach statistical significance. This is the first study in which the two novel 3'end prothrombin gene variants, FIIc.*64_*66del and FlI c.*303T>C, were reported. PMID- 26148379 TI - Does brucellosis cause arterial stiffness and ventricular remodelling through inflammation? AB - BACKGROUND: Like other acute and chronic infections, Brucella infection leads to endothelial dysfunction. Furthermore, it has been suggested that the chronic inflammatory state present in chronic infectious diseases leads to an acceleration in atherosclerosis. For the prediction of CAD, it is possible to use epicardial fat thickness (EFT) as an adjunctive marker beside the classical risk factors, as it is easily and non-invasively evaluated by transthoracic echocardiography. The purpose of this study was to investigate the presence of impaired myocardial performance as well as of increased arterial stiffness and EFT in patients who had been infected with brucellosis in the past. METHODS: Included in the study were twenty-seven brucellosis patients and twenty-six healthy volunteers. Using EFT and transthoracic echocardiography, which included Doppler echocardiography in combination with tissue Doppler imaging (TDI), all the patients were examined to measure their aortic stiffness index (AoSI), aortic distensibility (AoD), and aortic elastic modulus (AoEM) values. RESULTS: A statistically significant increase was observed in hs-CRP, aortic stiffness index, aortic elastic modulus and EFT in brucellosis patients when compared with the controls (2.46 +/- 1.40 vs. 1.71 ? 0.61, P=0.016; 9.69 +/- 6.99 vs. 2.14 +/- 0.72, P < 0.001; 11.17 +/- 8.60 vs 2.18 +/- 0.90, P < 0.001; 0.76 +/- 0.08 vs. 0.63 +/- 0.10, P < 0.001). On the other hand, there was a significant decrease in aortic strain and aortic distensibility (7.41 ? 6.82 vs 18.26 +/- 5.83, P < 0.001; 1.83 +/- 1.71 vs. 5.22 +/- 1.72, P < 0.001, respectively). No difference was observed between the two groups with respect to the left ventricular myocardial performance index (MPI) (0.62 +/- 0.15 vs. 0.61 +/- 0.13, P=0.859). CONCLUSIONS: In this study, we demonstrated for the first time in the literature thatthere was impaired aortic elasticity and increased EFT in patients with brucellosis, while the myocardial performance index remained unaffected. We also determined that these effects had a significant correlation with inflammation. PMID- 26148380 TI - Education is critical for medication adherence in patients with coronary heart disease. AB - BACKGROUND: Although non-adherence to medications is associated with increased cardiovascular risks, very little information is focused on the relationship between knowledge and medication adherence among patients with coronary heart disease (CHD). AIM: The purposes were to assess the relationship between medication adherence and medication- or disease-related knowledge in patients with CHD, and to investigate whether educating patients would alter their medication adherence behaviour. METHODS: This study was carried out at the outpatient clinic of a public university teaching hospital in China.The primary outcome was the ability of patients to follow medication instructions, which was assessed by the Morisky Medication Adherence Scale (MMSA-8). The Medication- or Disease-Related Knowledge Test (MDRKT) was used to assess patients'medication related knowledge. We also explored patients'preferences for receiving education about medications and whether it is necessary for pharmacists to provide education. RESULTS: Among the 159 patients who completed the survey, approximately 38.4% were considered non-adherent (MMAS-8 score <6). Medication- or disease-related knowledge and concerns about adverse drug events were significantly associated with non-adherence. The MDRKT revealed that most participants had very little knowledge about their drug treatment. Specifically, 22 participants said that pharmacists were their primary source of information. Subsequently, 95.0% of participants expressed an interest in activities related to medication education. CONCLUSIONS: Knowledgeable patients with CHD are more likely to adhere to medication instructions. Many patients have difficulty acquiring medication information; thus, patients need increased access to education about their medication. Pharmacist services may be required to provide such information. PMID- 26148381 TI - The additive value of multiple biomarkers in prediction of premature coronary artery disease. AB - OBJECTIVE: The aim of this study was to determine the value of additional multiple biomarkers in the prediction of premature coronary artery disease (CAD). METHODS AND RESULTS: Data from 503 CAD patients and 503 healthy control patients with matching age and sex were collected. The patient group consisted of male (25 to 55 years) and female (30 to 60 years) patients with documented angiographic multi-vessel CAD. Baseline characteristics of conventional risk factors and biomarkers were collected. We compared the conventional risk factors model with the model with six additional biomarkers (hs-CRP, IL-6, RAGE, Lp-LPA2, adiponectin, and RANTES), which have shown significant association with premature CAD. We also evaluated the effects of adding each of the six biomarkers to the conventional laboratory data. The additional biomarkers model resulted in improvements in the C-statistic (0.953 vs. 0.937, P=0.0003) in comparison with the conventional risk factors model. Among the 6 biomarkers added to the patient group, hs-CRP and IL-6 had a significant discriminative power to predict the risk of premature CAD (hs-CRP; P = 0.0005, IL-6; P= 0.003). CONCLUSIONS: Although conventional risk factors were more strongly associated with premature CAD than were biomarkers, adding the 6 biomarkers (hs-CRP, IL-6, RAGE, Lp-LPA2, adiponectin, and RANTES) improved the prediction of premature CAD moderately. We found that hs-CRP and IL-6 had shown a significant contribution in the prediction of premature CAD. PMID- 26148382 TI - Underestimated and unreported prolonged QTc by automated ECG analysis in patients on methadone: can we rely on computer reading? AB - BACKGROUND: Recognition of prolonged corrected QT (QTc) interval is of particular importance, especially when using medications known to prolong QTc interval. Methadone can prolong the QTc interval and has the potential to induce torsades de pointes. OBJECTIVE: The objective of this study is to investigate the accuracy of computerized ECG analysis in correctly identifying and reporting QTc interval in patients on methadone. METHODS: We conducted a retrospective review of ECGs in the Muse electronic database of patients on methadone who are above 18 years old between January 2012 and December 2013 at an urban community hospital. ECGs were analyzed by the Marquette 12SL ECG Analysis Program (GE'Healthcare) reviewed by a cardiologist. RESULTS: A total of 826 ECGs of patients on methadone were examined manually for the QTc interval, of which 625 (75.7%) had QTc less than 470 ms, 149 (18%) had QTc between 470-499 ms and 52 (6.3%) had QTc more than 499 ms. QTc between 470-499 ms was underestimated by machine in 19 (12.8%) ECGs and QTc more than 499 ms was underestimated in 10 (19.6%) when compared to manually calculated QTc. QTc prolongation was underreported in 63 ECGs (48.5%) of those whose QTc between 470-499 ms and in 1 ECG (2.4%) of those whose QTc was more than 499 ms. CONCLUSIONS: QTc can be underestimated or unreported by the computer analysis. Physicians not only should calculate QTc manually but also examine the actual QTc value displayed on the report before concluding that this parameter is normal, especially in patients who are at risk of QTc prolongation. PMID- 26148383 TI - The efficacy of tolvaptan as a diuretic for chronic kidney disease patients. AB - BACKGROUND: Tolvaptan selectively binds to the vasopressin V2 receptor and inhibits reabsorption of free water. Although its efficacy for heart failure has been proven, its efficacy for chronic kidney disease (CKD) patients has not been assessed in detail. METHODS: We examined 20 CKD patients (13 men and 7 women) who presented with volume overload and who were administered tolvaptan. We assessed urine volume (UV) and blood biochemistry before administration (dO), 1 day after administration (d1), and 7 to 14 days after administration (d7-14). RESULTS: The mean age was 74.0 +/- 13.1 years. Besides CKD, there were 9, 8, and 5 patients with heart failure, liver failure or liver cirrhosis, andsevere oedema, respectively. UV significantly increased from 959.0 +/- 503.8 mL/day at d0 to 1605.4 +/- 964.0 mL/day at d7-14 (P<0.01). Serum creatinine levels were not exacerbated (3.89 +/- 3.43 mg/dL at d0 and 3.66 +/- 3.02 mg/dL at d7-14). Serum albumin (ALB) levels and urinary protein creatinine ratio (uPCR) did not correlate with UV change. Estimated glomerular filtration rate (eGFR) correlated with UV change from d0 to d1 (r=0.6619, P<0.01). Serum sodium elevation correlated with increased UV (r=0.4951, P<0.05). CONCLUSION: Tolvaptan is useful to reduce volume overload without exacerbation of the renal function; its effect does not depend on ALB or uPCR. the eGFR correlated with the efficacy of tolvaptan. If UV increases drastically after tolvaptan administration, serum Na levels should be carefully monitored. PMID- 26148384 TI - Dynamic changes of repolarization abnormalities in takotsubo cardiomyopathy. AB - OBJECTIVE: This study analyses dynamicchangesin dispersion of ventricularrepolarization over the time course of takotsubo cardiomyopathy (TC), and their relationships with clinical features and life-threatening arrhythmias. METHODS AND RESULTS: All consecutive patients admitted to our division between January 2008 and December 2011 with a diagnosis of TC were analysed. Patients with prior myocardial infarction, symptoms-onset-to-admission time greater than 12 hours, an implanted pacemaker, or under treatment with drugs affecting QTinterval, were excluded. Standard 12-lead ECG recordings during the acute, subacute and chronic phases were collected for each patient. Twenty-four patients (23 women, 63 +/- 14 years) were includedin our analysis. Only one patient experienced ventricular arrhythmias (4.2%). Significant increases were observed in QT and QTc intervals (from 420 ?423 to 505 +/- 66 ms, P < 0.00001, and from 479 +/- 33 to 551 +/- 51 ms, P < 0.00001, respectively), QTdispersion (from 59 +/ 18 to 100 +/- 44 ms, P=0.0006), Tpeak-to-Tend (from 82 +/- 20 to 123 +/- 39 ms, P=0.00006) and Tpeak-to-Tend/QT (from 0.20 +/- 0.33 to 0.26 +/- 0.57, P=0.0003) during the subacute phase. All these parameters returned to baseline values in the chronic phase and did not show any significant differences between the acute and chronic phases. CONCLUSIONS: A marked increase in QTc, QT dispersion, Tpeak to-Tend and Tpeak-to-Tend/QT was observed during the subacute phase; this increase was transient and reverted in allpatients before hospital discharge. Ofnote, these findings were not associated with an increased risk of life threatening arrhythmias. PMID- 26148385 TI - Spinal cord stimulation in refractory angina. A systematic review of randomized controlled trials. AB - OBJECTIVE: Spinal cord stimulation (SCS) is an invasive method used for treating patients with refractory angina. Although SCS is recommended by the European Society of Cardiology and American Heart Association (class lib, level of evidence B and C, respectively), the method is used very rarely and data on its effectiveness is limited. The aim of this work was to perform a systematic review of all randomized controlled trials (RCTs) that investigated the effectiveness of SCS as a treatment for refractory angina. METHODS: Medline and Cochrane library databases were searched from their inception to April 2014 for RCTs that investigated the efficacy and safety of SCS in patients with refractory angina. RESULTS: Nine RCTs were included in the systematic review. The included RCTs were categorized into two groups: RCTs comparing SCS either with optimal medical treatment or inactive mode or low stimulation SCS; and those comparing SCS with alternative therapeutic interventions. Follow-up was short-term (1-6 months) in most studies, showing no major complications. Two studies reported a neutral effect regarding mortality. Regarding efficacy, most RCTs were in favour of SCS mainly in the short term. The most recent, multi-centre RCT reported no significant difference compared to the control group. CONCLUSIONS: RCTs investigating the efficacy of SCS were small and they demonstrated a small effect in angina improvement. Due to great differences in their design the interpretation of the results is complex. Before this method is recommended as a routine therapy for refractory angina, a larger, well-designed, multicentre RCT is needed. PMID- 26148386 TI - Hypertrophic cardiomyopathy: obstruction flushed out with exercise echocardiography. PMID- 26148387 TI - Cardiac ischaemia following BIB-placement. PMID- 26148388 TI - New onset atrial fibrillation due to isolated cor triatriatum in a middle-aged woman. PMID- 26148389 TI - Neovascularization of lung carcinoma originating from single coronary artery. PMID- 26148390 TI - [MESSAGE FROM THE PRESIDENT]. PMID- 26148391 TI - CERVICAL CYTOLOGY TRENDS IN A SAMPLE OF INFLAMMATORY BOWEL DISEASE PATIENTS IN PUERTO RICO: A DESCRIPTIVE STUDY AND RESEARCH OF CURRENT LITERATURE. AB - OBJECTIVE OF THE STUDY: To describe cervical cytology trends in a sample of patients with Inflammatory Bowel Disease (IBD) and to provide an overview of aspects such as contraception and menstrual patterns. STUDY DESIGN: We identified women with diagnosis of IBD of ages between 21-49 years followed at the IBD clinics of the Medical Sciences Campus from June 2012 to April 2014. A 15-minute questionnaire was administered. Data was entered and analyzed calculating frequencies and percentages. RESULTS: Sixty-three subjects were recruited. After reviewing the questionnaires, 52 subjects remained for analysis. All women were between 21 and 49 years of age. Thirty (58%) patients had a diagnosis of ulcerative colitis (UC), while 22 (42%) patients had Crohn's Disease (CD). Twenty seven IBD patients (52%) were in remission. Use of immunomodulators was reported in ten (33%) and seventeen (61%) of patients for UC and CD respectively. Sixty six percent (67%) of participants specified having their cervical cytology for cervical cancer screening done a nually. Twenty patients (38%) reported abnormal cytology including 13 patients (43%) with UC and 7 patients (23%) with CD. No significant relation was found between the two conditions and the self-reported history of abnormal cervical cytology. Almost one-half of IBD patients reported a menstrual cycle of 25-30 days (45%). Duration of menses was described as normal (lasting between 4-6 days) in 45% of IBD patients (95% CI 31.13-59.66). Patients with UC were more likely to report regular menses than patients with CD. Eighty six percent of participants reported no use of contraception. CONCLUSION: This is the first descriptive report of gynecologic conditions in which Puerto Rican patients with IBD have been studied. It is imperative to continue with similar larger studies to gain a broader idea of what are the gynecological needs of this population. PMID- 26148392 TI - FINGERTIP RECONSTRUCTION WITH THE "SHARK MOUTH" INCISION THENAR FLAP: ANALYSIS OF OUTCOMES IN PEDIATRIC PATIENTS. AB - The thenar flap technique is a time-tested method of fingertip reconstruction that has been criticized due to possible finger flexion contractures and unsightly donor site scars. Functional outcome data on thenar flaps on the pediatric population is poor in the medical literature. METHOD: In this retrospective chart review we acquired information from sixteen patients who underwent a "Shark Bite" incision thenar flap reconstruction. RESULTS: Patients ranged in age from 0-17 years. Time to division ranged from 16-30 days. All 16 patients' affected finger ROM were measured in DIP, PIP and MCP joints and compared with corresponding finger on contralateral hand. A questionnaire measured subjective satisfaction in: sensibility, appearance, and function. Fingertip sensation was preserved in both affected finger and donor site. The most persistent patient complaint involved fingertip contour, were most patients rated it as "Fair"(43%) and "Good" (56%). After statistical analysis of the data we found no statistical difference in range of motion (ROM) between affected finger and the same finger on the contralateral hand on both PIP and MCP joints (p=0.08, 0.06 respectively). CONCLUSIONS: The "Shark Mouth" incision thenar flap is an effective strategy for fingertip reconstruction. The results demonstrate this technique has excellent functional and aesthetic results and is not associated with flexion contractures, excessive sensibility or pain in the pediatric population. PMID- 26148393 TI - THE RELATIONSHIP BETWEEN DIABETES MELLITUS AND BODY MASS INDEX: PRIMARY CARE FACILITY IN PUERTO RICO. AB - Obesity is a major risk factor in the development of Diabetes Mellitus (DM). Body Mass Index (BMI), an estimation based on the persons weight and height, helps identify patients at risk to develop DM. We report the relationship between DM and BMI using data from a primary care facility in Puerto Rico. METHOD: Patients were chosen at random with the only requirement to be included in this study was age over 50. A population of 200 patients was obtained and each participant was categorized by gender, weight, height, BMI and their status as a known diabetic or not. RESULTS: In respect to the diabetic population identified, which totaled 67 patients, 1 out of 67 (1%) were underweight, 14 out of 67 (20%) were normal, 28 out of 67 (42%) were overweight, and 24 out of 67 (36%) obese. CONCLUSION: 78% of the diabetic population fell in the categories of either overweight or obese. BMI increases the incidence of Diabetes Mellitus in patients older than 50 years of age. PMID- 26148394 TI - UNCOMMON PRESENTATION OF FOLLICULAR THYROID CARCINOMA: WHEN CHRONIC BACK PAIN SHOULD RAISE A FLAG. AB - Follicular thyroid carcinoma is the second most common type of thyroid cancer, and its incidence has increased dramatically in recent years. Although it typically presents as a thyroid nodule, it can spread to distant sites via hematogenous dissemination. Spinal cord compression complicating thyroid carcinoma is rare with only few cases reported in the literature. This case illustrates a minimally invasive follicular carcinoma that showed such an aggressive behavior, and thus the importance of considering metastatic thyroid carcinoma in the differential diagnosis of chronic back pain, which may possibly progress to spinal cord compression carrying severe morbidity. PMID- 26148395 TI - ANAL LARGE CELL NEUROENDOCRINE CARCINOMA WITH TUBULOVILLOUS ADENOMA COEXISTENCE: A CASE REPORT. AB - Anal poorly differentiated neuroendocrine carcinomas are very rare aggressive neoplasm with a poor prognosis. This high-grade malignancy carcinoma can have small or non-small cells composition. This case report illustrates a large cell anal neuroendocrine carcinoma with tubulovillous component. PMID- 26148396 TI - PRIMARY IMMUNE REFRACTORY THROMBOCYTOPENIA IN ASSOCIATION WITH SECONDARY DISORDERS: A CASE REPORT. AB - Immune thrombocytopenia is an autoimmune disorder characterized by immunologic destruction of platelets. It may occur in isolation or in association with other health disorders. We describe a case were the pathology involved an immune mediated mechanism initially thought to be isolated and posteriorly linked to secondary causes. PMID- 26148397 TI - GRANULOMATOSIS WITH POLYANGIITIS IN PUERTO RICO: CASE REPORTS. AB - Wegener's Granulomatosis or Granulomatosis with Polyangiitis (WG/GPA) is one of the antineutrophil cytoplasmic antibody associated vasculitis. Ocular manifestations the first presenting signs in patients with WG/GPA. We report on two patients diagnosed with WG/GPA and discuss their pertinent clinical findings. Our case report reviews the most common clinical manifestations and ophthalmic associations to compare them with the physical findings of two Hispanic patients. Further, to our knowledge this is the first report of ocular findings in patients with WG/GPA in two Puerto Rican patients. PMID- 26148398 TI - THE ROLE OF NUCLEAR IMAGING IN TRAUMATIC HEPATOPLEURAL FISTULA: A CASE REPORT. AB - Penetrating injuries are a major cause of mortality and morbidity. The most common diagnostic tool used in this setting is CT scan. We present a case of a traumatic hepatopleural fistula demonstrated by hepatobiliary scintigraphy. Traumatic abdominal injuries to the liver and diaphragm can result in complications, whose detection by CT scan is not always straightforward. Hepatobiliary scintigraphy is very useful in the search of bilious pleural effusions. PMID- 26148399 TI - THE USE OF A FIBULAR STRUT ALLOGRAFT WITH DBM, CANCELLOUS CHIPS AND BMP FOR A 10 CM HUMERAL SHAFT INFECTED NON-UNION: A CASE REPORT. AB - Humeral shaft non-unions occur in 2-10% of all fracture cases. Increased incidence of these non-unions can be associated with ORIF, comminution, high impact injuries, bone loss or fracture gaping. Treatment guidelines for fracture non-union state that fractures with gaps greater than 4 cm should be treated with vascularized fibular autografts or transportation with an external fixator. Unfortunately these modalities carry considerable donor site morbidity and patient will experience considerable discomfort, especially when dealing with an external fixator. This report demonstrates how the use of a nonvascularized fibular strut can be effectively utilized as an alternate treatment modality for large humeral shaft non-union gaps. Further studies should be conducted to support this method as a viable treatment option for non-union gaps greater than 4 cm. PMID- 26148400 TI - A VERY RARE NEOPLASM IN AN IMMUNOCOMPETENT PATIENT. AB - Kaposi's sarcoma is a rare malignancy requiring infection with human Herpes virus for development. We report a case of a 76-year-old immunocompetent male with recurrent leg cellulitis. The cellulitis eventually developed into a non-healing ulcer and a palpable nodule consistent with nodular Kaposi's sarcoma. PMID- 26148401 TI - A TRAUMATIC BILATERAL FEMORAL NECK FRACTURES IN A HEALTHY PREMENOPAUSAL FEMALE WITH HYPOVITAMINOSIS D. AB - Bilateral atraumatic femur neck fractures in young adult are very rare. We report a young premenopausal female with osteormalacia secondary to vitamin D deficiency and spontaneous bilateral femur neck fractures. Patient had no reported risk factors for osteomalacia but hypovitaminosis D was noted upon evaluation. Osteomalacia secondary to low serum levels of vitamin D may lead to stress and fragility fractures. Identification and treatment of such patients may decrease the incidence of stress fractures and- possible complications. PMID- 26148402 TI - [POTENTIALLY FATAL LYELL SYNDROME]. AB - Toxic epidermal necrolysis or Lyell's syndrome is a rare entity with strong compromise of immune system. It is a hypersensitivity reaction secondary to the use of specific drugs and other triggers. Erythematous lesions of bullous aspect characterize the clinical picture affecting all layers of the skin, scaly and widespread in distribution and progression. Sometimes life threatening, generate a severe inflammatory and systemic reaction with multiple organ dysfunction. Treatment encompasses three objectives: identification and suspension of triggers, general clinical support and therapy to the skin lesions. Immune therapy is controversial and not supported by solid scientific evidence. We report a case that summarizes all aspects of this potentially lethal disease. PMID- 26148403 TI - [CHRONIC SUBDURAL HEMATOMA: PHYSIOPATHOLOGY AND SURGICAL MANAGEMENT]. AB - Chronic subdural hematoma is an encapsulated collection of blood underneath the Dura, essentially characterized by the presence of a membrane. It usually occurs in the elderly considered as a sentinel event. Simple brain computed tomography is the current imaging aid of choice for the diagnosis of this entity. It should be suspected especially in patients who present with dementia syndrome. Although less frequent, it should be investigated in patients with transient neurologic deficit. There is still no consensus regarding the ideal surgical modality of treatment. The procedure that seems most recommended is closed suction drainage through burr holes. It has been controversial whether intraoperative washing of such collection improves outcomes. PMID- 26148404 TI - [Yes, that also!]. PMID- 26148405 TI - [Oral health saves lives]. PMID- 26148406 TI - [Interprofessional team for better oral health]. PMID- 26148407 TI - [Look into the mouth of the residents]. PMID- 26148408 TI - [News spreads fast]. PMID- 26148409 TI - [Individual care and clinical competence]. PMID- 26148410 TI - [Finding the suitable nursing home]. PMID- 26148411 TI - [Bullying in Swiss nursing homes]. PMID- 26148412 TI - [Success experiences and building projects]. PMID- 26148413 TI - [Making eHealth in nursing visible]. PMID- 26148414 TI - ["Ethics boom" in health care]. PMID- 26148415 TI - [Cursing and laughing are liberating]. PMID- 26148416 TI - [Challenges of today]. PMID- 26148417 TI - [The "what to do" project]. PMID- 26148418 TI - [Adolescents and contraception: let's talk!]. PMID- 26148419 TI - [The added value of nurses]. PMID- 26148421 TI - [The details that count]. PMID- 26148420 TI - [Opening the window]. PMID- 26148423 TI - TERT Promoter Mutations in Papillary Thyroid Microcarcinomas. AB - BACKGROUND: Small papillary thyroid carcinomas have contributed to the worldwide increased incidence of differentiated thyroid cancer observed over the past decades. However, the mortality rate has not changed over the same period of time, raising questions about the possibility that thyroid cancer patients, especially those with small tumors, are overdiagnosed and overtreated. Molecular prognostic marker able to discriminate aggressive thyroid cancers from those with an indolent course would be of great relevance to tailor the therapeutic approach and reduce overtreatment. Mutations in the TERT promoter were recently reported to correlate strongly with aggressiveness in advanced forms of thyroid cancer, holding promise for a possible clinical application. The occurrence and potential clinical relevance of TERT mutations in papillary thyroid microcarcinomas (mPTCs) is currently unknown. This study aimed to analyze the occurrence of two TERT promoter mutations (-124C>T and -146C>T) and their potential association with unfavorable clinical features in a large cohort of mPTCs. METHODS: A total of 431 mPTCs cases were collected from six Italian institutions, and TERT promoter mutational status was assessed by a next-generation sequencing approach. RESULTS: TERT promoter mutations were found in 4.7% of the analyzed mPTCs, showing that even microcarcinomas carry mutations in this gene. Correlation analysis showed that TERT promoter mutations are not associated with aggressive features or clinical outcome in the cohort analyzed. CONCLUSIONS: TERT mutations are present but uncommon in mPTCs. Apparently, in mPTCs, the occurrence of TERT mutations is not correlated with unfavorable clinical features. PMID- 26148424 TI - Current concepts in vulvodynia with a focus on pathogenesis and pain mechanisms. AB - Vulvodynia is a common and debilitating chronic pain syndrome characterised by neuropathic-type pain. Localised provoked vulvodynia is the most common type, followed by generalised unprovoked vulvodynia. Vulvodynia is a diagnosis of exclusion. The cause is unknown but current research suggests an underlying predisposition to increased sensitivity to pain and peripheral and central neural sensitisation. Musculoskeletal factors also play an important role. Vulvodynia has a significant impact on the quality of life, mood, functional ability and relationships of patients and their partners. It is highly associated with anxiety and depression. Treatment needs to follow a biopsychosocial model and be tailored to the patient. A multimodal and multidisciplinary approach is often most effective. We have suggested a therapeutic ladder. PMID- 26148425 TI - Metal bioavailability in freshwater sediment samples and their influence on ecological status of river basins. AB - The general aim of this work has been to check the ecological impact of metals on the Ebro river basin. In order to evaluate this, metal behavior considering water, sediment as well as metal bioaccumulation in fish has been studied. Total concentrations of metals, as well as the potentially bioavailable fraction of metals in sediment has also been analyzed by the application of the sequential extraction method (BCR method). In order to evaluate the influence of metal pollution on the river ecological status, according to the Water Framework Directive (WFD), diverse biological indices such as macroinvertebrates (IBMWP), diatoms (IPS) and macrophytes (IVAM), have been considered from an integrated point of view. Considering both water and sediment, metals which contributed in higher extend to the reduction of biological quality have been demonstrated to be Pb and Zn, as they presented a negative influence on macroinvertebrates, diatoms and macrophytes communities. As and Cr that seemed to have a significant influence on macroinvertebrates and diatoms too, while Ni negatively influenced only diatom communities. This study also demonstrated that monitoring programs only based on total metal determination in water are inefficient, as metals present even at undetectable concentrations in water are strongly accumulated in fish. Moreover, the high concentrations of Hg found in sediments indicated that this river basin may present pollution problems regarded to this metal, as demonstrated by the high Hg levels found in fish. PMID- 26148427 TI - ? PMID- 26148426 TI - Ecological relevance of biomarkers in monitoring studies of macro-invertebrates and fish in Mediterranean rivers. AB - Mediterranean rivers are probably one of the most singular and endangered ecosystems worldwide due to the presence of many endemic species and a long history of anthropogenic impacts. Besides a conservation value per se, biodiversity is related to the services that ecosystems provide to society and the ability of these to cope with stressors, including climate change. Using macro-invertebrates and fish as sentinel organisms, this overview presents a synthesis of the state of the art in the application of biomarkers (stress and enzymatic responses, endocrine disruptors, trophic tracers, energy and bile metabolites, genotoxic indicators, histopathological and behavioural alterations, and genetic and cutting edge omic markers) to determine the causes and effects of anthropogenic stressors on the biodiversity of European Mediterranean rivers. We also discuss how a careful selection of sentinel species according to their ecological traits and the food-web structure of Mediterranean rivers could increase the ecological relevance of biomarker responses. Further, we provide suggestions to better harmonise ecological realism with experimental design in biomarker studies, including statistical analyses, which may also deliver a more comprehensible message to managers and policy makers. By keeping on the safe side the health status of populations of multiple-species in a community, we advocate to increase the resilience of fluvial ecosystems to face present and forecasted stressors. In conclusion, this review provides evidence that multi-biomarker approaches detect early signs of impairment in populations, and supports their incorporation in the standardised procedures of the Water Frame Work Directive to better appraise the status of European water bodies. PMID- 26148428 TI - Laryngeal sarcoidosis: presentation and management in the pediatric population. AB - BACKGROUND: Sarcoidosis is a disease characterized by systemic non-necrotizing granulomas of unknown etiology. Laryngeal sarcoidosis is extremely uncommon, especially among pediatric patients. The clinical presentation and management of this entity in the pediatric population are poorly understood. METHODS: A comprehensive search in PubMed was conducted to identify all cases in the published literature. We also present a case of isolated pediatric laryngeal sarcoidosis and outline the multidisciplinary approach to evaluation and management. RESULTS: A previously healthy 13-year-old female presented with a five-month history of mild dysphonia, dyspnea on exertion, and diffuse supraglottic edema. Biopsy showed non-necrotizing granulomas. Treatment with methotrexate led to marked improvement. The literature search identified seven previously published cases of pediatric laryngeal sarcoidosis, four in which disease was isolated to the larynx. All patients presented with a symptomatic and diffusely edematous supraglottis. Diagnoses were based on supraglottic biopsies showing non-necrotizing granulomas; all other possible etiopathologies were excluded. Three patients responded to corticosteroid therapy alone, one patient to tumor necrosis factor (TNF) inhibitor and methotrexate, and the remainder to a combination of corticosteroid therapy and surgical debulking. CONCLUSIONS: Laryngeal sarcoidosis in the pediatric population is challenging to diagnose and manage. When epithelioid granulomas are encountered histologically, other causes of granulomatous inflammation must be ruled out before a diagnosis of sarcoidosis can be made. Corticosteroid therapy alone may be ineffective. Medical therapy with methotrexate alone or in combination with TNF inhibitors versus surgical debulking alone or as part of multimodality treatment should be considered. A multidisciplinary approach with involvement of an otolaryngologist, pathologist, and rheumatologist is suggested. PMID- 26148429 TI - Pott's puffy tumor: a rare complication of acute otitis media in child: a case report. AB - To describe a rare case of Potts' puffy tumor (PPT) in the zygomatic area, which developed as a complication of acute otitis media in a 6-year-old child. To date, only one case of PPT has been described in the literature as a complication of latent mastoiditis in an adult, and one case of PPT as a complication of acute mastoiditis in a 10-year-old child. Urgent surgical intervention, including evacuation of the purulent lesion, removal of inflamed soft tissue and osteolysis of the involved bone, and antromastoidectomy, intravenous treatment with broad spectrum antibiotics, including G+, G-, anaerobes and fungi, and local therapy. PMID- 26148430 TI - Cyclodextrin-based PNN supramolecular assemblies: a new class of pincer-type ligands for aqueous organometallic catalysis. AB - Water-soluble cyclodextrins (CDs) bearing two nitrogen atoms as metal coordinating sites have been synthesized. An appropriate phosphane could be included within their cavity through the primary face to form self-assembled PNN supramolecular edifices. Once the PNN ligands were coordinated to platinum, the resulting complexes proved to be very effective as catalysts in a domino reaction, where a Pt-catalyzed reduction of nitrobenzene was followed by a Paal Knorr pyrrole reaction. In the nitrobenzene reduction, the modified CDs acted both as first- and second-sphere ligands. Contrary to an acyclic glucopyranose based NN ligand unable to interact with a phosphane ligand, the CD-based PNN ligands stabilized the catalytic species in water by supramolecular means. Interestingly, the product and the water-soluble Pt-catalyst could be recovered in two different phases once the reaction was complete. PMID- 26148431 TI - Package size and manufacturer-recommended serving size of sweet beverages: a cross-sectional study across four high-income countries. AB - OBJECTIVE: To assess the mean package size and manufacturer-recommended serving size of sweet beverages available in four high-income countries: Australia, Canada, the Netherlands and New Zealand. DESIGN: Cross-sectional surveys. SETTING: The two largest supermarket chains of each country in 2012/2013. SUBJECTS: Individual pack size (IPS) drinks (n 891) and bulk pack size (BPS) drinks (n 1904). RESULTS: For all IPS drinks, the mean package size was larger than the mean serving size (mean (sd)=412 (157) ml and 359 (159) ml, respectively). The mean (sd) package size of IPS drinks was significantly different for all countries (range: Australia=370 (149) ml to New Zealand=484 (191) ml; P<0.01). The mean (sd) package size of Dutch BPS drinks (1313 (323) ml) was significantly smaller compared with the other countries (New Zealand=1481 (595) ml, Australia=1542 (595) ml, Canada=1550 (434) ml; P<0.01). The mean (sd) serving size of BPS drinks was significantly different across all countries (range: Netherlands=216 (30) ml to Canada=248 (31) ml; P<0.00). New Zealand had the largest package and serving sizes of the countries assessed. In all countries, a large number of different serving sizes were used to provide information on the amount appropriate to consume in one sitting. CONCLUSIONS: At this point there is substantial inconsistency in package sizes and manufacturer recommended serving sizes of sweet beverages within and between four high-income countries, especially for IPS drinks. As consumers do factor serving size into their judgements of healthiness of a product, serving size regulations, preferably set by governments and global health organisations, would provide consistency and assist individuals in making healthier food choices. PMID- 26148432 TI - Deprescribing in patients with multimorbidity: a necessary process. PMID- 26148433 TI - Venous thromboembolism and preoperative steroid use: analysis of the NSQIP database to evaluate risk in surgical patients. AB - BACKGROUND: Despite several prophylactic strategies, postoperative venous thromboembolism (VTE) remains a major cause of morbidity and mortality. Therefore, the search for modifiable preoperative risk factors is crucial. Few reports have explored this issue but the direct relationship between preoperative steroid use and postoperative VTE in surgical patients remains unexplored. METHODS: We used The American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) database in our study. After analyzing patient characteristics, we used multivariate logistic regression to assess the crude and adjusted effect of steroids on VTE, our primary outcome. RESULTS: Data was obtained for 1,921,901 patients, 58,667 of whom were on glucocorticoids for at least 30days preoperatively. VTE was higher in patients on steroids with an adjusted odds ratio of 1.54, 95% confidence interval (CI) 1.45-1.64. The adjusted odds ratio for the secondary outcomes: mortality, urinary tract occurrences, wound occurrences, sepsis, cardiac and respiratory adverse events were 1.42 (CI 1.35-1.49), 1.40 (CI 1.30-1.50), 1.58 (CI 1.51-1.66), 1.51 (CI 1.42-1.60), 1.19 (CI 1.11-1.29) and 1.302 (CI 1.301-1.303) respectively. CONCLUSIONS: Our results suggest that surgical patients with prolonged preoperative glucocorticoid intake are at a higher risk of developing postoperative VTE as well as other secondary outcomes including: all-cause mortality, urinary tract occurrences, sepsis, wound occurrences, cardiac and respiratory adverse events. These are important findings since preoperative glucocorticoid use is a modifiable factor. PMID- 26148434 TI - Hydroxyl metabolite of PCB 180 induces DNA damage signaling and enhances the DNA damaging effect of benzo[a]pyrene. AB - Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) and their hydroxyl metabolites (OH-PCBs) are ubiquitous environmental contaminants in human tissues and blood. The toxicological impact of these metabolites is poorly understood. In this study rats were exposed to ultrapure PCB180 (10-1000mg/kgbw) for 28days and induction of genotoxic stress in liver was investigated. DNA damage signaling proteins (pChk1Ser317 and gammaH2AXSer319) were increased dose dependently in female rats. This increase was paralleled by increasing levels of the metabolite 3'-OH-PCB180. pChk1 was the most sensitive marker. In in vitro studies HepG2 cells were exposed to 1MUM of PCB180 and 3'-OH-PCB180 or the positive control benzo[a]pyrene (BaP, 5MUM). 3'-OH-PCB180, but not PCB180, induced CYP1A1 mRNA and gammaH2AX. CYP1A1 mRNA induction was seen at 1h, and gammaH2AX at 3h. The anti oxidant N-Acetyl-l-Cysteine (NAC) completely prevented, and 17beta-estradiol amplified the gammaH2AX induction by 3'-OH-PCB180. As 3'-OH-PCB180 induced CYP1A1, a major BaP-metabolizing and activating enzyme, interactions between 3' OH-PCB180 and BaP was also studied. The metabolite amplified the DNA damage signaling response to BaP. In conclusion, metabolism of PCB180 to its hydroxyl metabolite and the subsequent induction of CYP1A1 seem important for DNA damage induced by PCB180 in vivo. Amplification of the response with estradiol may explain why DNA damage was only seen in female rats. PMID- 26148435 TI - Arsenic-induced S phase cell cycle lengthening is associated with ROS generation, p53 signaling and CDC25A expression. AB - Cellular response to arsenic is strongly dependent on p53 functional status. Primarily arresting the cell cycle in G1 or G2/M phases, arsenic treatment also induces an increase in the S-phase time in wild-type p53 cells. In contrast, cells with a non-functional p53 display only a subtle increase in the S phase, indicating arsenic differentially affects the cell cycle depending on p53 status. Importantly, it has been reported that arsenic induces reactive oxygen species (ROS), a process counteracted by p53. To evaluate the participation of p53 in the lengthening of the S phase and the connection between the transient cell cycle arrest and oxidative stress, we evaluated the cell response to arsenic in MCF-7 and H1299 cells, and analyzed p53's role as a transcription factor in regulating genes involved in ROS reduction and S phase transition. Herein, we discovered that arsenic induced an increase in the population of S phase cells that was dependent on the presence and transcriptional activity of p53. Furthermore, for the first time, we demonstrate that arsenic activates p53-dependent transcription of ROS detoxification genes, such as SESN1, and by an indirect mechanism involving ATF3, genes that could be responsible for the S phase cell cycle arrest, such as CDC25A. PMID- 26148436 TI - About the article: Prevalence of lower urinary tract symptoms in individuals with down syndrome. PMID- 26148437 TI - Current opinions regarding care of the mature pediatric urology patient. AB - INTRODUCTION: With continued improvements in pediatric urology care of patients with complex congenital genitourinary conditions, many survive into adulthood. This fact has created a challenging situation of transitioning from pediatric to adult care. Establishing long-term follow-up with appropriate specialists is a critical part of a successful transition to adulthood for this population. OBJECTIVE: This study sought to elucidate current practices and opinions regarding the management of adult complex genitourinary patients by pediatric urologists, in order to determine if a consensus for adult care exists. STUDY DESIGN: An anonymous, 15-question online survey was created to address practice patterns and opinions regarding the transition of care of complex genitourinary patients. An invitation to participate was distributed via email to 200 pediatric urologists who were members of the American Urological Association. Complex genitourinary patients were defined broadly as those with a history of: spina bifida, bladder exstrophy, cloacal exstrophy, cloacal anomalies, posterior urethral valves or disorders of sex development. Fisher's exact test was used for analysis. RESULTS: The response rate was 31.0% (62/200). Two-thirds (67.7%) cared for adults with complex genitourinary conditions. Overall, 51.6% of pediatric urologists felt that general urologists best follow adult patients, but only 6.5% recommended this for patients with prior complex genitourinary reconstruction (P < 0.001). Instead, the majority (80.6%) felt that a pediatric or adult urologist with an interest and training in adolescent/transitional urology who routinely performs such procedures would provide optimal care. Follow-up by a primary care physician alone was not recommended. Recommendations did not change if patients had developmental delay or lived independently (P = 0.47 and P = 0.72, respectively). Overall, 69.4% would refer mature complex genitourinary patients to a urologist with interest and training in adolescent/transitional urology, if one was available. However, only 45.2% had such an individual available in their practice (P < 0.001). DISCUSSION: In the present study, the opinions of pediatric urologists regarding optimal providers of long-term follow-up for mature complex genitourinary patients were presented. While the results may not represent the views of the entire pediatric urology community, responses from motivated individuals with a particular interest in transition care may be especially valuable. Although the present study did not outline a mechanism for improving transitional care, it offered valuable information on prevailing opinions in this area. Finally, the opinions of mostly North American Pediatric Urologists were presented, which may not apply to other healthcare settings. CONCLUSIONS: Pediatric urologists appeared to be virtually unanimous in recommending that urologists provide the most appropriate long-term follow-up of patients with congenital genitourinary conditions. Specifically, 80% recommended that patients with prior complex surgical reconstruction be followed by a urologist with specific interest, training and experience in the area of transitional urology. The data suggest that this may be an unmet need of these specialists and may signify the need for specific training in the care of such patients. PMID- 26148438 TI - Commentary to 'Combined creatinine velocity and nadir creatinine: A reliable predictor of renal outcome in neonatally diagnosed posterior urethral valves'. PMID- 26148439 TI - Commentary to: Association of BMI and pediatric urologic postoperative events: Results from pediatric NSQIP. PMID- 26148440 TI - Onlay foreskin flap anastomosed directly to the tunica albuginea: a short-term experimental study in rabbits. AB - INTRODUCTION: In severe hypospadias, urethral plate division is necessary for curvature correction. To configure the new urethra, an approach has been described using a foreskin flap directly anastomosed in an 'onlay' fashion to the tunica albuginea of the corpora cavernosa. Results suggest that it is possible to use the corpus cavernosum albuginea as the posterior wall of the neourethra without the need of a dorsal graft. OBJECTIVE: The present experimental study aimed to evaluate the histological characteristics and healing pattern of this procedure. STUDY DESIGN: Sixteen New Zealand male rabbits were divided into two groups of eight animals. Eight animals underwent 1-cm longitudinal dorsal incision of the penile urethra and the edges were anastomosed to the tunica albuginea (Group 1). Eight other animals underwent complete excision of 1.0 cm of penile urethra. Urethroplasty was performed using a foreskin flap directly anastomosed as an onlay to the albuginea, as shown in the figure (Group 2). Sacrifice and histological assessment was performed 2, 4, 8 and 12 weeks postoperatively. RESULTS: In Group 1, a mild inflammatory process was noted that became almost imperceptible at 12 weeks. Fibrosis was mild at all stages in this group. Over time, a regenerative epithelium covered the corpus cavernosum. Immunohistochemistry using specific CK-7 and CK-20 confirmed the presence of urothelium. No complications were microscopically detected in this group. Group 2 presented with a more intense inflammatory infiltrate, which also resolved over time. Fibrosis was slightly more intense in this group, especially in animals that had urethral strictures. Group 2 presented with three fistulas, two were associated with urethral stricture. Histological evaluation showed the presence of epithelization over the albuginea, which turned out to be similar to the normal urothelium over time and was confirmed by immunohistochemistry. Non keratinized stratified squamous epithelium of the foreskin flap showed good integration to the urethra. DISCUSSION: Microscopic analysis showed that inflammation, fibrosis and complications were similar to previous studies. At 12 weeks there was a well-developed epithelium similar to normal urethra, which was confirmed by immunohistochemistry; this was similar to what occurs in the TIP technique, as previously demonstrated. It was hypothesized that the epithelium regeneration developed from the urethral edges, as demonstrated in other experimental studies. CONCLUSION: The albuginea was covered by mature urothelium after 12 weeks, which presumably grew from the urethral edges. The foreskin flap onlay that was directly anastomosed to the albuginea completely integrated and constituted the roof of the neourethra. PMID- 26148441 TI - Children's Surgical Centers Physician Training and Experience or Institutional Requirements: What does the data say? PMID- 26148442 TI - Obituary - Judson Graves Randolph M.D.: 1927-2015. PMID- 26148443 TI - SD-OCT to distinguish papilledema from pseudopapilledema. AB - CASES REPORT: Two patients presented with headache and bilateral papillary edema. Patient 1 was found to have a papilledema (P) with intracranial pressure of 32cmH2O. Patient 2 was found to have a migraine with a pseudopapilledema (PP) (optic nerve head drusen). SD-OCT was used to image the optic disc, subretinal hyporeflective space (SHS), and alpha-angle (Aalpha). DISCUSSION: Optic disc SD OCT may be useful for differentiating disc morphology in P and PP. The area of the SHS and the Aalpha were higher in the P patient than in the patient with PP. PMID- 26148444 TI - Back to the future: An online OSCE Management Information System for nursing OSCEs. AB - BACKGROUND: The Objective Structured Clinical Examination (OSCE) is an established tool in the repertoire of clinical assessment methods in nurse education. The use of OSCEs facilitates the assessment of psychomotor skills as well as knowledge and attitudes. Identified benefits of OSCE assessment include development of students' confidence in their clinical skills and preparation for clinical practice. However, a number of challenges exist with the traditional paper methodology, including documentation errors and inadequate student feedback. OBJECTIVES: To explore electronic OSCE delivery and evaluate the benefits of using an electronic OSCE management system. To explore assessors' perceptions of and attitudes to the computer based package. DESIGN: This study was conducted using electronic software in the management of a four station OSCE assessment with a cohort of first year undergraduate nursing students delivered over two consecutive years (n=203) in one higher education institution in Ireland. A quantitative descriptive survey methodology was used to obtain the views of the assessors on the process and outcome of using the software. METHODS: OSCE documentation was converted to electronic format. Assessors were trained in the use of the OSCE management software package and laptops were procured to facilitate electronic management of the OSCE assessment. Following the OSCE assessment, assessors were invited to evaluate the experience. RESULTS: Electronic software facilitated the storage and analysis of overall group and individual results thereby offering considerable time savings. Submission of electronic forms was allowed only when fully completed thus removing the potential for missing data. The feedback facility allowed the student to receive timely evaluation on their performance and to benchmark their performance against the class. CONCLUSIONS: Assessors' satisfaction with the software was high. Analysis of assessment results can highlight issues around internal consistency being moderate and examiners variability. Regression analysis increases fairness of result calculations. PMID- 26148446 TI - Chronic fatigue syndrome and circulating cytokines: A systematic review. AB - There has been much interest in the role of the immune system in the pathophysiology of chronic fatigue syndrome (CFS), as CFS may develop following an infection and cytokines are known to induce acute sickness behaviour, with similar symptoms to CFS. Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a search was conducted on PubMed, Web of Science, Embase and PsycINFO, for CFS related-terms in combination with cytokine-related terms. Cases had to meet established criteria for CFS and be compared with healthy controls. Papers retrieved were assessed for both inclusionary criteria and quality. 38 papers met the inclusionary criteria. The quality of the studies varied. 77 serum or plasma cytokines were measured without immune stimulation. Cases of CFS had significantly elevated concentrations of transforming growth factor-beta (TGF-beta) in five out of eight (63%) studies. No other cytokines were present in abnormal concentrations in the majority of studies, although insufficient data were available for some cytokines. Following physical exercise there were no differences in circulating cytokine levels between cases and controls and exercise made no difference to already elevated TGF-beta concentrations. The finding of elevated TGF-beta concentration, at biologically relevant levels, needs further exploration, but circulating cytokines do not seem to explain the core characteristic of post-exertional fatigue. PMID- 26148445 TI - MicroRNAs mediating CNS inflammation: Small regulators with powerful potential. AB - MicroRNAs (miRNAs) are a family of small non-coding RNAs (~22 nucleotides) that fine-tune protein expression by either silencing mRNA translation or directly targeting gene transcripts for degradation. In the central nervous system (CNS), neuroinflammation plays a critical role in brain injury and neurodegeneration. Increasing evidence supports the involvement of miRNAs as key regulators of neuroinflammation. Altered expression or function of particular miRNAs has been identified in various CNS pathological conditions, including neuroinflammation, neurodegeneration, and autoimmune diseases. Several miRNAs have been shown to play a critical role in the microglia-mediated inflammatory response including miR-155 and miR-146a. In this review, we summarize recent advances in the field of miRNAs associated with CNS inflammation, including our studies of unique inflammatory pathways involving miR-155 and miR-146a. We discuss how specific miRNAs influence microglia activation states in response to inflammatory stimuli, and describe the potential of miRNAs as both biomarkers of inflammation and therapeutic tools for the modulation of microglia behavior. PMID- 26148447 TI - Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity. AB - Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2 null mice (MT-/-) and corresponding wild-type (MT+/+) mice was investigated to determine any associations with MT. Each MT-/- or MT+/+ mouse was pretreated with a single dose of DU (10mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT-/- mice significantly increased than in MT+/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT-/- mice. The apoptosis rate in MT-/- mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT-/- mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT-/- mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. PMID- 26148449 TI - Corrigendum: Interfacial dominated ferromagnetism in nanograined ZnO: a MUSR and DFT study. PMID- 26148448 TI - Metabolic activation of hepatotoxic drug (benzbromarone) induced mitochondrial membrane permeability transition. AB - The risk of drug-induced liver injury (DILI) is of great concern to the pharmaceutical industry. It is well-known that metabolic activation of drugs to form toxic metabolites (TMs) is strongly associated with DILI onset. Drug-induced mitochondrial dysfunction is also strongly associated with increased risk of DILI. However, it is difficult to determine the target of TMs associated with exacerbation of DILI because of difficulties in identifying and purifying TMs. In this study, we propose a sequential in vitro assay system to assess TM formation and their ability to induce mitochondrial permeability transition (MPT) in a one pot process. In this assay system, freshly-isolated rat liver mitochondria were incubated with reaction solutions of 44 test drugs preincubated with liver microsomes in the presence or absence of NADPH; then, NADPH-dependent MPT pore opening was assessed as mitochondrial swelling. In this assay system, several hepatotoxic drugs, including benzbromarone (BBR), significantly induced MPT in a NADPH-dependent manner. We investigated the rationality of using BBR as a model drug, since it showed the most prominent MPT in our assay system. Both the production of a candidate toxic metabolite of BBR (1',6-(OH)2 BBR) and NADPH dependent MPT were inhibited by several cytochrome P450 (CYP) inhibitors (clotrimazole and SKF-525A, 100MUM). In summary, this assay system can be used to evaluate comprehensive metabolite-dependent MPT without identification or purification of metabolites. PMID- 26148450 TI - Aortic Dilatation Associated With a De Novo Mutation in the SOX18 Gene: Expanding the Clinical Spectrum of Hypotrichosis-Lymphedema-Telangiectasia Syndrome. AB - BACKGROUND: We report a 13-year-old female patient followed since birth for multiple rare congenital defects, including hypotrichosis, telangiectasia, and severe dilatation of the ascending aorta. METHODS: Comprehensive phenotype assessment throughout childhood included repeated echocardiographic measurements, evaluation of renal function, and immunohistochemical analysis of skin biopsy samples. Whole-exome sequencing was performed for the patient and both unaffected parents. RESULTS: We identified a novel de novo mutation in the transcription factor SOX18 (c.481C>T:p.Gln161*) in the patient, which was absent in all unaffected family members. Echocardiography revealed early onset and progressive dilatation of the ascending aorta. Skin biopsy results confirmed the defects of the blood vasculature in the presence of intact lymphatic vessels. Assessment of renal function did not show any signs of renal problems or renal failure in the patient. CONCLUSIONS: The genetic finding of a pathogenic SOX18 mutation enabled the diagnosis of the rare hypotrichosis-lymphedema-telangiectasia syndrome in our patient. The identification of a novel stop gain mutation in the SOX18 gene in association with dilatation of the aorta highlights the importance of this gene during the development of the circulatory system. Our study highlights the importance of whole-exome sequencing in the rapid identification of genes and gene mutations involved in rare conditions and thus expanding the knowledge and spectrum of clinical manifestations associated with them. PMID- 26148451 TI - Arbuscular mycorrhiza improve growth, nitrogen uptake, and nitrogen use efficiency in wheat grown under elevated CO2. AB - Effects of the arbuscular mycorrhizal (AM) fungus Rhizophagus irregularis on plant growth, carbon (C) and nitrogen (N) accumulation, and partitioning was investigated in Triticum aestivum L. plants grown under elevated CO2 in a pot experiment. Wheat plants inoculated or not inoculated with the AM fungus were grown in two glasshouse cells with different CO2 concentrations (400 and 700 ppm) for 10 weeks. A (15)N isotope labeling technique was used to trace plant N uptake. Results showed that elevated CO2 increased AM fungal colonization. Under CO2 elevation, AM plants had higher C concentration and higher plant biomass than the non-AM plants. CO2 elevation did not affect C and N partitioning in plant organs, while AM symbiosis increased C and N allocation into the roots. In addition, plant C and N accumulation, (15)N recovery rate, and N use efficiency (NUE) were significantly higher in AM plants than in non-AM controls under CO2 enrichment. It is concluded that AM symbiosis favors C and N partitioning in roots, increases C accumulation and N uptake, and leads to greater NUE in wheat plants grown at elevated CO2. PMID- 26148453 TI - Non-anaemic iron deficiency impairs response to pulmonary rehabilitation in COPD. AB - BACKGROUND AND OBJECTIVE: Non-anaemic iron deficiency (NAID) might alter the oxygen pathway in health and disease. The current study aims at assessing the impact of NAID on aerobic capacity in patients with chronic obstructive pulmonary disease (COPD). METHODS: A prospective sample of 70 non-anaemic COPD patients candidate to participate in an 8-week pulmonary rehabilitation (PR) programme was studied. Incremental cycling exercise to peak oxygen uptake (V'O2peak ) and constant work-rate exercise at 80% V'O2peak to exhaustion were assessed pre- and post-PR. Training-induced increase of endurance time (ET) >=33%, which represented the minimal clinically important difference, classified patients as responders to exercise training. RESULTS: The prevalence of NAID was 48% (n = 34) showing no relationship with the Global Initiative for Chronic Obstructive Lung Disease stages (P = 0.209). Patients with NAID showed lower pre-training ET (P = 0.033) and V'O2peak (P = 0.007) than normal iron status (NIS) patients after adjustment for potential covariates. Significant training-induced physiological changes were seen in the NIS group (DeltaV'O2peak 68(132) mL/min; P = 0.009), but not in the NAID group (DeltaV'O2peak 26 (126) mL/min; P = 0.269). The NAID group showed lower percentage of responders to training (56%) than the NIS group (78%) (P = 0.041). CONCLUSIONS: COPD patients with NAID showed lower pre-training aerobic capacity and reduced training-induced response than NIS patients after adjusting for potential confounding variables. PMID- 26148452 TI - Air Pollution-Induced Vascular Dysfunction: Potential Role of Endothelin-1 (ET-1) System. AB - Exposure to air pollution negatively impacts cardiovascular health. Studies show that increased exposure to a number of airborne pollutants increases the risk for cardiovascular disease progression, myocardial events, and cardiovascular mortality. A hypothesized mechanism linking air pollution and cardiovascular disease is the development of systemic inflammation and endothelium dysfunction, the latter of which can result from an imbalance of vasoactive factors within the vasculature. Endothelin-1 (ET-1) is a potent peptide vasoconstrictor that plays a significant role in regulating vascular homeostasis. It has been reported that the production and function of ET-1 and its receptors are upregulated in a number of disease states associated with endothelium dysfunction including hypertension and atherosclerosis. This mini-review surveys epidemiological and experimental air pollution studies focused on ET-1 dysregulation as a plausible mechanism underlying the development of cardiovascular disease. Although alterations in ET 1 system components are observed in some studies, there remains a need for future research to clarify whether these specific changes are compensatory or causally related to vascular injury and dysfunction. Moreover, further research may test the efficacy of selective ET-1 pharmacological interventions (e.g., ETA receptor inhibitors) to determine whether these treatments could impede the deleterious impact of air pollution exposure on cardiovascular health. PMID- 26148455 TI - The passive voice. PMID- 26148454 TI - Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma. AB - Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and beta2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues have limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors that have been reported as targets of siRNA-mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages, and dendritic cells, which could potentially be applied in asthma therapy. PMID- 26148456 TI - Attached to meat? (Un)Willingness and intentions to adopt a more plant-based diet. AB - In response to calls to expand knowledge on consumer willingness to reduce meat consumption and to adopt a more plant-based diet, this work advances the construct of meat attachment and the Meat Attachment Questionnaire (MAQ). The MAQ is a new measure referring to a positive bond towards meat consumption. It was developed and validated through three sequential studies following from an in depth approach to consumer representations of meat. The construct and initial pool of items were firstly developed drawing on qualitative data from 410 participants in a previous work on consumers' valuation of meat. Afterwards, 1023 participants completed these items and other measures, providing data to assess item selection, factor structure, reliability, convergent and concurrent validity, and predictive ability. Finally, a sample of 318 participants from a different cultural background completed the final version of the MAQ along with other measures to assess measurement invariance, reliability and predictive ability. Across samples, a four-factor solution (i.e., hedonism, affinity, entitlement, and dependence) with 16 items and a second-order global dimension of meat attachment fully met criteria for good model fit. The MAQ subscales and global scale were associated with attitudes towards meat, subjective norm, human supremacy beliefs, eating habits, and dietary identity. They also provided additional explanatory variance above and beyond the core TPB variables (i.e. attitudes, subjective norm and perceived behavioral control) in willingness and intentions concerning meat substitution. Overall, the findings point towards the relevance of the MAQ for the study of meat consumption and meat substitution, and lend support to the idea that holding a pattern of attachment towards meat may hinder a shift towards a more plant-based diet. PMID- 26148457 TI - Perceptions and attitudes towards food choice in adolescents in Gaborone, Botswana. AB - The purpose of this qualitative study was to describe the factors that influence adolescent and adult perceptions and attitudes related to adolescent diet in Botswana. A series of 15 focus groups [12 adolescent focus groups (6 male and 6 female) & 3 parent focus groups] of approximately six to eleven members each were conducted in Gaborone, the capital city of Botswana in 2009-2010. Adolescents and parents of adolescents suggest that the main drivers of adolescent food choices have much to do with where the adolescent is in terms of time of day as well as with whom the adolescent is with. Outside of the home adolescents suggest that the real or perceived influence of companions place social standing on the ability to purchase and consume non-traditional foods, and that traditional foods leave adolescents open to ridicule. Additionally parents of adolescents suggest that while they prefer for their children to consume healthy foods, they frequently purchase unhealthy food items for their children based on the child's taste preferences as well as social influence to prove you can buy "nice things" for one's family. Adolescents and parents of adolescents suggest that increasing the availability and decreasing the costs of healthy food options are preferred possible interventions to increase healthful eating among adolescents. However, the adolescents also suggest that these healthy food options should not crowd out or completely replace unhealthy options, thus preserving the adolescents' freedom to choose. This could pose a major challenge in any school-based adolescent obesity prevention program. PMID- 26148458 TI - Regulating Current Rectification and Nanoparticle Transport Through a Salt Gradient in Bipolar Nanopores. AB - Tuning of ion and nanoparticle transport is validated through applying a salt gradient in two types of nanopores: the inner wall of a nanopore has bipolar charges and its outer wall neutral (type I), and both the inner and outer walls of a nanopore have bipolar charges (type II). The ion current rectification (ICR) behavior of these nanopores can be regulated by an applied salt gradient: if it is small, the degree of ICR in type II nanopore is more significant than that in type I nanopore; a reversed trend is observed at a sufficiently large salt gradient. If the applied salt gradient and electric field have the same direction, type I nanopore exhibits two significant features that are not observed in type II nanopore: (i) a cation-rich concentration polarization field and an enhanced funneling electric field are present near the cathode side of the nanopore, and (ii) the magnitude of the axial electric field inside the nanopore is reduced. These features imply that applying a salt gradient to type I nanopore is capable of simultaneously enhancing the nanoparticle capture into the nanopore and reducing its translocation velocity inside, so that high sensing performance and resolution can be achieved. PMID- 26148459 TI - Irrelevance of Carbon Monoxide Poisoning in the Methanol Oxidation Reaction on a PtRu Electrocatalyst. AB - Based on detailed in situ attenuated total-reflection-surface-enhanced IR reflection absorption spectroscopy (ATR-SEIRAS) studies of the methanol oxidation reaction (MOR) on Ru/Pt thin film and commercial Johnson-Matthey PtRu/C, a revised MOR enhancement mechanism is proposed in which CO on Pt sites is irrelevant but instead Pt-Ru boundary sites catalyze the oxygen insertion reaction that leads to the formation of formate and enhances the direct reaction pathway. PMID- 26148460 TI - [Skin disorders in malignant hematologic diseases]. AB - Numerous cutaneous manifestations have been reported in patients with hematologic malignancies. This review provides an overview on this subject by dividing skin lesions into three main groups: (1) skin disorders due to vascular changes (dilatation, occlusion and inflammation), (2) unspecific (e.g. paleness, opportunistic infections) and specific skin lesions (e.g. leukemia cutis), and (3) the large group of paraneoplastic skin disorders. Emphasis is placed on clinical findings and therapeutic options of those paraneoplastic syndromes that are most frequently found in hematologic malignancies. PMID- 26148461 TI - Quantifying bonding strength of CuO nanotubes with substrate using the nano scratch technique. AB - CuO is a narrow bandgap semiconductor demonstrating applications in/as catalysts, gas sensors, adsorbents, and superconductors, and as electrodes of photocells, super-capacitors, and lithium-ion batteries. One-dimensional (1D) CuO nanostructures are of particular interest in most of these device applications, owing to their huge surface area. Strong bonding between nanomaterials and substrate is essential for extended device life. Hence, knowledge about the strength of the nanomaterial-substrate bond is highly desired. In this research work, CuO nanotubes were synthesized directly on a Cu substrate, and its adhesion strength was quantified using the nano-scratch-based technique. The adhesion energy of CuO nanotubes (for 7 h of reaction period) on the Cu substrate was measured to be 82 Jm(-2). The bonding strength can be correlated with the structure of the material. Results of this research will be valuable in analyzing and improving the lifetime of CuO nanotube-based devices, and the technique could be further extended to other 1D transition metal oxide nanostructures. PMID- 26148462 TI - Arthroscopically assisted stabilization of displaced lateral clavicle fractures with coracoclavicular instability. AB - BACKGROUND: Lateral clavicle fractures associated with partial or complete injury of the coracoclavicular ligaments have traditionally been treated using a variety of open surgical techniques. PURPOSE OF THE STUDY: The aim of this prospective study was the evaluation of the clinical and radiologic outcome of displaced lateral clavicular fractures with coracoclavicular instability treated in an arthroscopic single TightRope technique including an interfragmentary cerclage. METHODS: From 2008 to 2010, 23 patients [8 women and 15 men; mean age 38 (24-63) years] who sustained a displaced lateral clavicular fracture type II according to Neer were included in this study. The follow-up consisted of a complete physical examination of the shoulder including range of motion, the constant score (CS), and the subjective shoulder value (SSV). The radiological follow-up included an anteroposterior stress view with 10 kg of axial load and bilateral axillary views to evaluate the coracoclavicular distance, the clavicular implant position, and healing of the fracture. RESULTS: After a mean follow-up of 23.0 (13-38) months, 20 patients (7 women and 13 men; mean age 38.3 (24-53) years) were available for follow-up. On average, patients achieved 95.1 (60-100) % in the SSV, 88.7 (64-99; contralateral side 91.8 points; p > 0.05) points in the CS. Radiologically, 18 of 20 patients (90 %) displayed a bony healing of the fracture. The average coracoclavicular distance of 11.2 (6-14) mm did not differ significantly from the healthy side [9.9 (8-14) mm]. In six cases (30 %), coracoclavicular ossifications appeared. Two of 20 patients had concomitant glenohumeral lesions (10 %). Two patients had secondary surgery [implant removal (N = 1 local implant irritation); plate osteosynthesis (N = 1 early loss of reduction)]. CONCLUSION: The arthroscopic-assisted and image intensifier-controlled closed reduction and single TightRope fixation with interfragmentary cerclage of displaced lateral clavicular fractures with coracoclavicular instability yields excellent clinical results and is able to recreate stability of the clavicle. PMID- 26148463 TI - Atypical features in depression: Association with obesity and bipolar disorder. AB - OBJECTIVES: Depression with atypical features amounts to a significant proportion of depressed patients. Studies have shown its association with bipolarity and, recently, with obesity. In this study, we investigated atypical features of depression in relation to overweight/obesity in three diagnostic categories: unipolar depression, bipolar depression and dysthymia. METHODS: Out of 512 depressed patients screened, we recruited 182 research subjects, consisting of 91 pairs, matched by age, gender and diagnosis, in which one member of the pair was within the normal weight range (BMI<=25) and the other was either overweight or obese (BMI>25). There were 35 pairs with unipolar depression, 27 with bipolar depression and 29 with dysthymia. Symptoms of atypical depression, such as increased appetite, hypersomnia, leaden paralysis, longstanding pattern of interpersonal rejection sensitivity, and, a significant weight gain in the past 3 months, were assessed. RESULTS: All the symptoms of atypical depression were significantly more pronounced in those depressed patients with a BMI>25, compared with depressed subjects with a normal weight. Except for hypersomnia, these symptoms scored significantly higher in women compared to men. Among the diagnostic categories, symptoms of atypical depression were significantly higher in patients with bipolar disorder compared with both major depressive disorder and dysthymia. LIMITATIONS: The preponderance of women, the assessment of atypical depression by adaptation of the DSM criteria, entirely Polish population, specificity of selection criteria. CONCLUSIONS: The results demonstrated a higher intensity of atypical depression's symptoms in overweight/obese depressed patients. They also confirm the association between obesity and bipolarity. PMID- 26148464 TI - Psychometric properties of the Portuguese version of the Acceptance and Action Questionnaire-Trauma Specific (AAQ-TS): A study with Portuguese Colonial War Veterans. AB - BACKGROUND: The Acceptance and Action Questionnaire-Trauma Specific (AAQ-TS) is a self-report measure designed to assess-trauma-related psychological (in)flexibility, as conceptualized in Acceptance and Commitment Therapy. However, there are no studies to date regarding its psychometric properties. This study explores such properties in the Portuguese version of the AAQ-TS, in Portuguese Colonial War Veterans. METHOD: A Principal Components Analysis (PCA) was conducted in a sample from the general population of war Veterans (N=371). Confirmatory Factor Analysis (CFA) as well as reliability and convergent validity studies were performed in a different sample from the same population (N=312). For the discriminant validity a clinical sample with a war-related PTSD (N=42) and a non-clinical sample without PTSD (N=44) were used. RESULTS: The CFA suggested a re-specified 15-item model with good global adjustment and factorial validity. The AAQ-TS showed internal consistency, a good temporal reliability, convergent validity with psychopathological symptoms (related to PTSD, anxiety, depression and stress) and peritraumatic dissociation (altered awareness and depersonalization/derealization). The questionnaire also discriminates between war Veterans with and without a PTSD diagnosis. LIMITATIONS: The major limitation relates to the samples' characteristics and sampling methods, which can limit the generalization of results. CONCLUSION: The Portuguese version of the AAQ-TS is a reliable and valid measure to assess experiential avoidance related to trauma in Portuguese Colonial War Veterans. PMID- 26148465 TI - Enhanced inflammatory and T-helper-1 type responses but suppressed lymphocyte proliferation in patients with seasonal affective disorder and treated by light therapy. AB - BACKGROUND: Animals show seasonal changes in the endocrine and immune system in response to winter stressors. Even though increased inflammation has been implicated in the pathophysiology of depression, whether immune disorder is a key mediator in seasonal affective depression (SAD) is unknown. Here, we hypothesized that short photoperiods in winter may induce inflammatory response, which contributes to SAD, and that light treatments should normalize immune function and improve depressive symptoms. METHODS: Twenty patients with a diagnosis of SAD, and a score on the HAM-29 of 20 or higher were recruited for this study. Twenty-one healthy subjects with no personal and family history of psychiatric disorder were matched to patients according to age and sex. Patients and controls were sampled during winter between November and January, inclusive. A subset of SAD patients (N=13) was re-sampled after 4 weeks of light therapy. Blood samples were assayed for macrophage activity, lymphocyte proliferation and cytokine release. RESULTS: SAD patients showed significantly higher macrophage activity and lower lymphocyte proliferation in winter compared to healthy subjects. The concentrations of macrophage-produced proinflammatory cytokines interleukin-1beta and tumour necrosis factor-alpha, and T-helper (Th)-1 produced cytokine, interferon-gamma were all significantly increased. In contrast, no significant changes in Th2-produced cytokines were observed. Light therapy significantly improved depressive scores, which was associated with attenuation of decreased lymphocyte functions, increased macrophage activity and level of proinflammatory cytokines. CONCLUSION: SAD patients have increased macrophage and Th1 type responses in winter, and light therapy normalized immune functions and depressive symptoms. These results support an inflammatory hypothesis for SAD and an immunomodulatory role of light therapy. PMID- 26148466 TI - Clinical and molecular characteristics of bloodstream infections caused by Candida albicans in children from 2003 to 2011. AB - We investigated the clinical and molecular characteristics of Candida albicans bloodstream infection (BSI) in children from a tertiary-level medical centre in Taiwan over a 9-year period from January 2003 to December 2011. We performed multilocus sequence typing (MLST) to investigate the genetic relatedness of these C. albicans BSI isolates. A total of 79 episodes of C. albicans BSI in 76 paediatric patients were identified, including 41 (51.9%) from the paediatric intensive care unit, 24 (30.4%) from the neonatal intensive care unit and 14 (17.7%) from general wards. More than half (59.5%) of these patients had underlying chronic co-morbidities, and the majority (94.9%) had a catheter or some other artificial device. All the isolates were susceptible to the antifungal agents tested. Only 32.9% (26/79) received effective antifungal agents within 24 h of onset of candidaemia. Twenty-five (31.6%) patients had persistent candidaemia (>3 days after the start of antifungal treatment) and candidaemia attributable mortality rate was 22.8% (18/79). The 72 isolates available for MLST yielded 53 unique diploid sequence types (DSTs). Forty-five DSTs were singletons and eight DSTs were shared by 27 (37.5%) isolates. Seventy-one (98.6%) isolates were clustered within previously known clades. Based on the definition of two or more strains with shared DST occurring within a period of 90 days, 10.1% of the infections were categorized as nosocomial clusters, most commonly identified in the intensive care units. Although cluster-associated candidaemia was not associated with a higher mortality rate, none of the clusters were identified by the hospital infection control team. PMID- 26148467 TI - Reporting guidelines for population pharmacokinetic analyses. AB - The purpose of this work was to develop a consolidated set of guiding principles for the reporting of population pharmacokinetic (PK) analyses based on input from a survey of practitioners as well as discussions between industry, consulting, and regulatory scientists. The survey found that identification of population covariate effects on drug exposure and support for dose selection (in which population PK frequently serves as preparatory analysis for exposure-response modeling) are the main areas of influence for population PK analysis. The proposed guidelines consider 2 main purposes of population PK reports: (1) to present key analysis findings and their impact on drug development decisions, and (2) as documentation of the analysis methods for the dual purpose of enabling review of the analysis and facilitating future use of the models. This work also identified 2 main audiences for the reports: (1) a technically competent group responsible for in-depth review of the data, methodology, and results; and (2) a scientifically literate but not technically adept group, whose main interest is in the implications of the analysis for the broader drug development program. We recommend a generalized question-based approach with 6 questions that need to be addressed throughout the report. We recommend 8 sections (Synopsis, Introduction, Data, Methods, Results, Discussion, Conclusions, Appendix) with suggestions for the target audience and level of detail for each section. A section providing general expectations regarding population PK reporting from a regulatory perspective is also included. We consider this an important step toward industrialization of the field of pharmacometrics such that a nontechnical audience also understands the role of pharmacometric analyses in decision making. Population PK reports were chosen as representative reports to derive these recommendations; however, the guiding principles presented here are applicable for all pharmacometric reports including pharmacokinetics/pharmacodynamics and simulation reports. PMID- 26148470 TI - Chemometrics meets homeopathy--an exploratory analysis of infrared spectra of homeopathic granules. AB - 10 homeopathic remedies commercially available (each in 3 dilutions) as sugar granules, where half of them were of organic (and half inorganic) origin were subjected to solid-state infrared spectroscopy, both in middle infrared (ATR FTIR) and near infrared (NIR) range. Measurements were repeated six times (six days, each sample was measured once in the same day, samples were measured in random order). The obtained spectra was subjected to unsupervised (PCA) and supervised (PLS-DA) chemometric techniques to check any visible differnces in spectral data between homeopathic remedies, including also feature selection approaches. It can be concluded that the only one information encoded in this dataset is the atmospheric drift of spectra between consecutive measurement days. This proves that homeopathy is not "infrared visible" in the case of proper experimental design. These results can be useful in further investigations of possible mechanisms of action of homeopathy (if they exist). PMID- 26148471 TI - Cthrc1 controls adipose tissue formation, body composition, and physical activity. AB - OBJECTIVE: This study investigated the effects of loss of Cthrc1 on adipogenesis, body composition, metabolism, physical activity, and muscle physiology. METHODS: Complete metabolic and activity monitoring as well as grip strength measurements and muscle myography was performed in Cthrc1 null and wildtype mice. RESULTS: Compared to wildtypes, Cthrc1 null mice had similar body weights but significantly reduced energy expenditure, decreased lean mass, and increased fat mass, especially visceral fat. In vitro studies demonstrated that Cthrc1 inhibited adipocyte differentiation as well as PPAR and CREB reporter activity, while preadipocytes isolated from Cthrc1 null mice exhibited enhanced adipogenic differentiation. Voluntary physical activity in Cthrc1 null mice as assessed by wheel running was reduced to approximately half the distance covered by wildtypes. Reduced grip strength was observed in Cthrc1 null mice at the age of 15 weeks or older with reduced performance and mass of hyphenate muscle. In the brain, Cthrc1 expression was most prominent in neurons of thalamic and hypothalamic nuclei with evidence for secretion into the circulation in the median eminence. CONCLUSIONS: Our data indicate that Cthrc1 regulates body composition through inhibition of adipogenesis. In addition, central Cthrc1 may be a mediator of muscle function and physical activity. PMID- 26148472 TI - Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members. AB - Pachymic acid (PA) is a lanostane-type triterpenoid derived from Poria cocos mushroom that possess various biological effects such as anti-cancer, antiinflammatory and anti-metastasis effects. In this study, we investigated the anti-cancer effects of PA in EJ bladder cancer cells. The results showed that PA significantly inhibited proliferation of EJ cells in a dose-dependent manner. PA induced accumulation of sub-G1 DNA content (apoptotic cell population), apoptotic bodies and chromatin condensation and DNA fragmentation in EJ cells in a dose dependent manner. PA also induces activation of caspase-3, -8 and -9, and subsequent cleavage of poly (ADP-ribose) polymerase, and significantly suppressed the inhibitor of apoptosis protein family proteins in a dose-dependent manner. Furthermore, PA activates Bid and induced the loss of mitochondrial membrane potential (DeltaPsim ) with up-regulated pro-apoptotic proteins (Bax and Bad), down-regulated anti-apoptotic proteins (Bcl-2 and Bcl-xL) and cytochrome c release. In turn, PA increased the generation of reactive oxygen species (ROS); also, the ROS production was blocked by N-acetyl-L-cysteine. The expressions of TNF-related apoptosis inducing ligand and death receptor 5 were up-regulated by PA in a dose-dependent manner, suggesting extrinsic pathway also involved in PA induced apoptosis. This study provides evidence that PA might be useful in the treatment of human bladder cancer. PMID- 26148473 TI - Atypical teratoid/rhabdoid tumor (ATRT) arising from the 3rd cranial nerve in infants: a clinical-radiological entity? AB - Atypical teratoid/rhabdoid tumor (ATRT) is a rare embryonal tumor of the central nervous system with preponderance in very young children, the majority of whom are younger than 3 years of age at diagnosis. Historically, outcomes of this aggressive disease, even with extensive multimodal therapy, have been dismal. Recent improvements have come from therapies directed exclusively towards ATRT, but misdiagnosis or delays in the correct diagnosis lead to significantly worse survival rates. ATRTs most commonly occur supratentorially but have been described in virtually all central nervous system locations, including the cerebellopontine angle cistern, meninges, and spinal canal, and extradural locations. ATRTs originating from cranial nerves are rare. Here, we describe three cases of solitary ATRT arising from the 3rd cranial nerve (CN III) or close to its origin in the midbrain, all of which presented in patients within 6 months of birth, with isolated unilateral oculomotor nerve palsy and strikingly similar magnetic resonance imaging (MRI) features. These MRI features include IV contrast enhancement, relative T2 hyposignal, and restricted water diffusion on apparent diffusion coefficient images, findings which are consistent with angiogenesis and high cellularity, and hence, suggestive of malignancy. We conclude that ATRT should be placed high on the differential diagnosis list when encountering a young infant presenting with isolated, unilateral 3rd nerve palsy and a small, solitary tumor arising from CN III that demonstrates malignant conventional and diffusion-weighted imaging features on MRI. PMID- 26148474 TI - Generation of cardiac spheres from primate pluripotent stem cells in a small molecule-based 3D system. AB - Pluripotent stem cell (PSC) usage in heart regenerative medicine requires producing enriched cardiomyocytes (CMs) with mature phenotypes in a defined medium. However, current methods are typically performed in 2D environments that produce immature CMs. Here we report a simple, growth factor-free 3D culture system to rapidly and efficiently generate 85.07 +/- 1.8% of spontaneously contractile cardiac spheres (scCDSs) using 3D-cultured human and monkey PSC spheres. Along with small molecule-based 3D induction, this protocol produces CDSs of up to 95.7% CMs at a yield of up to 237 CMs for every input pluripotent cell, is effective for human and monkey PSCs, and maintains 81.03 +/- 12.43% of CDSs in spontaneous contractibility for over three months. These CDSs displayed CM ultrastructure, calcium transient, appropriate pharmacological responses and CM gene expression profiles specific for maturity. Furthermore, 3D-derived CMs displayed more mature phenotypes than those from a parallel 2D-culture. The system is compatible to large-scaly produce CMs for disease study, cell therapy and pharmaceutics screening. PMID- 26148475 TI - Growth of lanthanide-doped LiGdF4 nanoparticles induced by LiLuF4 core as tri modal imaging bioprobes. AB - Multimodal imaging can compensate for the deficiencies and incorporate the advantages of individual imaging modalities. In this paper, we demonstrated the synthesis of core-shell nanocomposites LiLuF4@LiGdF4:Yb,Er/Tm constituted of tetragonal LiLuF4 nanoparticles as core and Yb,Er/Tm-codoped LiGdF4 as shell. LiLuF4@LiGdF4:Yb,Er/Tm nanoparticles display brighter upconversion luminescence (UCL) than NaGdF4:Yb,Er/Tm nanoparticles with the same size under continuous-wave excitation at 980 nm. The active shell layer of LiGdF4:Yb,Er/Tm not only provide the UCL center, but also serve as magnetic resonance (MR) imaging contrast agent. To further improve the UCL intensity, the inert LiGdF4 shell was coated on the LiLuF4@LiGdF4:Yb,Er/Tm nanoparticles. Furthermore, LiLuF4@LiGdF4:Yb,Tm@LiGdF4 nanoparticles have been successfully applied to UCL/X-ray computed tomography (CT)/MR tri-modal imaging on the modal of tumor-bearing mice. PMID- 26148477 TI - Tissue performance of bladder following stretched electrospun silk fibroin matrix and bladder acellular matrix implantation in a rabbit model. AB - The goal of this study was to investigate the tissue performance of bladder following stretched electrospun silk fibroin matrix (SESFM) implantation compared with bladder acellular matrix (BAM). We compared SESFM with BAM based on porosity and pore size. Scaffolds were separately transplanted into opposite walls of the bladder of 30 rabbits after stripping the bladder mucosa and smooth muscle (1.5 * 2.0 cm(2)). Gross anatomical observation, histological analysis and muscle contractility studies were performed at 2, 4, and 8 weeks post-op. SESFM has higher porosity and larger pore size compared with BAM (p < 0.05). At 2 weeks, the presence of vesical calculus was evident in 7/10 rabbits. Histological analysis showed that SESFM and BAM promoted similar degree of urothelium regeneration (p > 0.05). However, SESFM promoted a higher degree of smooth muscle and vessel regeneration compared to BAM (p < 0.05). In addition, muscle strips supported by SESFM displayed higher contractile responses to carbachol, KCl, and phenylephrine compared with BAM. At 8 weeks, both matrices elicited similar mild acute and chronic inflammatory reactions. Our results demonstrated that SESFM has greater ability to promote bladder tissue regeneration with structural and functional properties compared to BAM, and with similar biocompatibility. PMID- 26148476 TI - Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients. AB - Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/beta-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16(INK4a). Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients. PMID- 26148478 TI - Cortical activation associated with determination of depth order during transparent motion perception: A normalized integrative fMRI-MEG study. AB - When visual patterns drifting in different directions and/or at different speeds are superimposed on the same plane, observers perceive transparent surfaces on planes of different depths. This phenomenon is known as transparent motion perception. In this study, cortical activities were measured using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to reveal the cortical dynamics associated with determination of depth order during transparent motion perception. In addition, offline eye movement measurements were performed to determine the latencies of the start of both pursuit eye movements and depth attention that are important in determination of the depth order. MEG and fMRI data were analyzed by a normalized integrative fMRI-MEG method that enables reconstruction of time-varying dipole moments of activated regions from MEG signals. Statistical analysis of fMRI data was performed to identify activated regions. The activated regions were used as spatial constraints for the reconstruction using the integrative fMRI-MEG method. We focused on the period between latencies (216-405 ms) determined by eye movement experiment, which are related to determination of the depth order. The results of integrative analysis revealed that significant neural activities were observed in the visual association area, the human middle temporal area, the intraparietal sulcus, the lateral occipital cortex, and the anterior cingulate cortex between 216 and 405 ms. These results suggest that initial eye movement and accompanying cortical activations during focused duration play an important role in determining the depth order during transparent motion perception. PMID- 26148479 TI - Targeted Recombinant Progeny: a design for ultra-high resolution mapping of Quantitative Trait Loci in crosses between inbred or pure lines. AB - BACKGROUND: High-resolution mapping of the loci (QTN) responsible for genetic variation in quantitative traits is essential for positional cloning of candidate genes, and for effective marker assisted selection. The confidence interval (QTL) flanking the point estimate of QTN-location is proportional to the number of individuals in the mapping population carrying chromosomes recombinant in the given interval. Consequently, many designs for high resolution QTN mapping are based on increasing the proportion of recombinants in the mapping population. The "Targeted Recombinant Progeny" (TRP) design is a new design for high resolution mapping of a target QTN in crosses between pure, or inbred lines. It is a three generation procedure generating a large number of recombinant individuals within a QTL previously shown to contain a QTN. This is achieved by having individuals that carry chromosomes recombinant across the target QTL interval as parents of a large mapping population; most of whom will therefore carry recombinant chromosomes targeted to the given QTL. The TRP design is particularly useful for high resolution mapping of QTN that differentiate inbred or pure lines, and hence are not amenable to high resolution mapping by genome-wide association tests. RESULTS: In the absence of residual polygenic variation, population sizes required for achieving given mapping resolution by the TRP-F2 design relative to a standard F2 design ranged from 0.289 for a QTN with standardized allele substitution effect = 0.2, mapped to an initial QTL of 0.2 Morgan to 0.041 for equivalent QTN mapped to an initial QTL of 0.02 M. In the presence of residual polygenic variation, the relative effectiveness of the TRP design ranges from 1.068 to 0.151 for the same initial QTL intervals and QTN effect. Thus even in the presence of polygenic variation, the TRP can still provide major savings. Simulation showed that mapping by TRP should be based on 30-50 markers spanning the initial interval; and on at least 50 or more G2 families representing this number of recombination points,. CONCLUSIONS: The TRP design can be an effective procedure for achieving high and ultra-high mapping resolution of a target QTN previously mapped to a known confidence interval (QTL). PMID- 26148480 TI - Why are older adults and individuals with underlying chronic diseases in Germany not vaccinated against flu? A population-based study. AB - BACKGROUND: Older adults and individuals with underlying chronic diseases are at increased risk of developing influenza-related complications and are target groups for seasonal influenza vaccination in many countries. In Germany, an annual national information campaign is conducted to increase influenza vaccination uptake in the target groups. However, data are lacking on knowledge and attitudes toward influenza vaccination among older adults and those with chronic diseases. The present study aimed to (i) estimate influenza vaccination uptake for the 2012/13 and 2013/14 seasons, (ii) assess knowledge and attitudes about influenza vaccination, and (iii) identify factors associated with vaccination uptake in two risk groups. METHODS: Between March and June 2014, we conducted a nationwide cross-sectional survey in adults (>=18 years) living in Germany using computer-assisted telephone interviewing. We calculated weighted vaccination coverage rates in two at-risk groups. Group 1 comprised participants aged 18-59 years with underlying chronic diseases. Group 2 comprised participants aged 60+, irrespective of underlying disease. We used univariate and multivariable logistic regression analyses to identify associations between influenza vaccination uptake and sociodemographic characteristics, and to evaluate attitudes and knowledge. RESULTS: In total, 1,519 interviews were conducted. Seasonal influenza vaccination uptake in people with underlying chronic diseases aged 18-59 years was 24 % in 2012/2013 and 23 % in 2013/2014. In older adults, uptake was 50 % and 49 % in 2012/13 and 2013/14 respectively. There were considerable vaccination-related knowledge gaps among respondents. For example, about half of the participants who aged >=60 years and/or suffered from underlying chronic diseases believed that influenza vaccination could cause influenza. The most commonly stated reasons for not being immunized were mistrust of the vaccination (22 %) and the perception that influenza is not dangerous (21 %). For both groups, vaccination uptake was independently associated with sex, perceived severity of influenza, perceived vaccination effectiveness, and the perceived likelihood or severity of vaccination side effects. For older adults, additional factors influencing vaccination uptake were age, underlying chronic diseases, and recent advice through physician consultation. CONCLUSIONS: Influenza vaccination coverage rates in Germany remain low. Individual perceptions regarding harms and benefits are crucial in the decision-making process. Communication strategies should focus on improving understanding and perception of personal risks arising from the disease and the vaccination. PMID- 26148481 TI - Improving access to skilled facility-based delivery services: Women's beliefs on facilitators and barriers to the utilisation of maternity waiting homes in rural Zambia. AB - BACKGROUND: Maternity waiting homes (MWHs) are aimed at improving access to facility-based skilled delivery services in rural areas. This study explored women's experiences and beliefs concerning utilisation of MWHs in rural Zambia. Insight is needed into women's experiences and beliefs to provide starting points for the design of public health interventions that focus on promoting access to and utilisation of MWHs and skilled birth attendance services in rural Zambia. METHODS: We conducted 32 in-depth interviews with women of reproductive age (15 45 years) from nine health centre catchment areas. A total of twenty-two in-depth interviews were conducted at a health care facility with a MWH and 10 were conducted at a health care facility without MWHs. Women's perspectives on MWHs, the decision-making process regarding the use of MWHs, and factors affecting utilisation of MWHs were explored. RESULTS: Most women appreciated the important role MWHs play in improving access to skilled birth attendance and improving maternal health outcomes. However several factors such as women's lack of decision-making autonomy, prevalent gender inequalities, low socioeconomic status and socio-cultural norms prevent them from utilising these services. Moreover, non availability of funds to buy the requirements for the baby and mother to use during labour at the clinic, concerns about a relative to remain at home and take care of the children and concerns about the poor state and lack of basic social and healthcare needs in the MWHs--such as adequate sleeping space, beddings, water and sanitary services, food and cooking facilities as well as failure by nurses and midwives to visit the mothers staying in the MWHs to ensure their safety prevent women from using MWHs. CONCLUSION: These findings highlight important targets for interventions and suggest a need to provide women with skills and resources to ensure decision-making autonomy and address the prevalent gender and cultural norms that debase their social status. Moreover, there is need to consider provision of basic social and healthcare needs such as adequate sleeping space, beddings, water and sanitary services, food and cooking facilities, and ensuring that nurses and midwives conduct regular visits to the mothers staying in the MWHs. PMID- 26148482 TI - Ultrasound measurement of optic nerve diameter and optic nerve sheath diameter in healthy Chinese adults. AB - BACKGROUND: Measurement of optic nerve sheath diameter (ONSD) is a fast and non invasive method in detecting elevated intracranial pressure. However, the reported normal range of ONSD was inconsistent. The objective of the study was to determine the normal range of ONSD in healthy Chinese adults. METHODS: Eyeball transverse diameter (ETD), optic nerve diameter (OND), and ONSD were measured by ultrasound examination in healthy adult volunteers. The OND and ONSD were assessed 3 mm behind the globe. The section showing maximal transverse diameter of the eyeball was frozen and the diameter was measured. Each ETD, OND and ONSD was examined twice and the mean value was calculated. RESULTS: A total of 519 healthy volunteers were included in the study. The median (interquartile range) of ETD, OND and ONSD were 22.3 (21.6 to 23.1) mm, 3.2 (2.9 to 3.4) mm, and 5.1 (4.7 to 5.4) mm, respectively. The 95% percentile of ONSD was 5.9 mm. There was no significant difference in ETD, OND or ONSD between male and female, or between left and right eye. ONSD was significantly correlated with OND (r = 0.62, P < 0.001), and the median OND/ONSD ratio (interquartile range) was 0.63 (0.59 to 0.67). CONCLUSIONS: The median and the 95% percentile of sonographic measurement of ONSD are 5.1 mm and 5.9 mm in healthy Chinese adults. The ONSD is correlated with OND, while independent of gender, age, height, weight and ETD. The median OND/ONSD ratio is 0.63 and this parameter warrants further investigation in patients with brain injury. PMID- 26148483 TI - Shedding metabo'light' on the search for sepsis biomarkers. AB - The clinical presentation of severe infection with generalized inflammation is similar, if not identical, to systemic inflammation induced by sterile tissue injury. Novel models and unbiased technologies are urgently needed for biomarker identification and disease profiling in sepsis. Here we briefly review the article of Kamisoglu and colleagues in this issue of Critical Care on comparing metabolomics data from different studies to assess whether responses elicited by endotoxin recapitulate, at least in part, those seen in clinical sepsis. PMID- 26148484 TI - Comparability between insecticide resistance bioassays for mosquito vectors: time to review current methodology? AB - BACKGROUND: Insecticides play an integral role in the control of mosquito-borne diseases. With resistance to insecticides on the rise, surveillance of the target population for optimal choice of insecticides is a necessity. The Centers for Disease Control and Prevention (CDC) bottle assay and the World Health Organization (WHO) susceptibility test are the most frequently used methods in insecticide resistance monitoring. However, the two bioassays differ in terms of insecticide delivery and how insecticide susceptibility is measured. To evaluate how equivalent data from the two assays are, we compared the two methods side-by side. METHODS: We did a literature search from 1998 to December 2014 to identify publications that performed both assays on the same mosquito population and compared the results. We then tested the WHO and CDC bioassays on laboratory strains of Aedes aegypti, Anopheles stephensi, An. gambiae and An. arabiensis with different insecticide resistance levels against permethrin, lambda cyhalothrin, DDT, bendiocarb and malathion. In addition, we also measured the relationship between time-to-knockdown and 24 h mortality. RESULTS: Both published data and results from the present laboratory experiments showed heterogeneity in the comparability of the two bioassays. Following their standard procedures, the two assays showed poor agreement in detecting resistance at the WHO cut-off mark of 90% (Cohen's kappa = 0.06). There was better agreement when 24 h mortality was recorded in the CDC bottle assay and compared with that of the WHO susceptibility test (Cohen's kappa = 0.5148). Time-to-knockdown was shown to be an unreliable predictor of 24 h mortality. CONCLUSION: Even though the two assays can detect insecticide resistance, they may not be used interchangeably. While the diagnostic dose in the WHO susceptibility test does not allow for detecting shifts at low or extreme resistance levels, time-to-knockdown measured in the CDC bottle assay is a poor predictor of 24 h mortality. Therefore, dose response assays could provide the most flexibility. New standardized bioassays are needed that produce consistent dose-response measurements with a minimal number of mosquitoes. PMID- 26148485 TI - Chemical gating of epitaxial graphene through ultrathin oxide layers. AB - We achieved a controllable chemical gating of epitaxial graphene grown on metal substrates by exploiting the electrostatic polarization of ultrathin SiO2 layers synthesized below it. Intercalated oxygen diffusing through the SiO2 layer modifies the metal-oxide work function and hole dopes graphene. The graphene/oxide/metal heterostructure behaves as a gated plane capacitor with the in situ grown SiO2 layer acting as a homogeneous dielectric spacer, whose high capacity allows the Fermi level of graphene to be shifted by a few hundreds of meV when the oxygen coverage at the metal substrate is of the order of 0.5 monolayers. The hole doping can be finely tuned by controlling the amount of interfacial oxygen, as well as by adjusting the thickness of the oxide layer. After complete thermal desorption of oxygen the intrinsic doping of SiO2 supported graphene is evaluated in the absence of contaminants and adventitious adsorbates. The demonstration that the charge state of graphene can be changed by chemically modifying the buried oxide/metal interface hints at the possibility of tuning the level and sign of doping by the use of other intercalants capable of diffusing through the ultrathin porous dielectric and reach the interface with the metal. PMID- 26148486 TI - Establishment of markerless gene deletion tools in thermophilic Bacillus smithii and construction of multiple mutant strains. AB - BACKGROUND: Microbial conversion of biomass to fuels or chemicals is an attractive alternative for fossil-based fuels and chemicals. Thermophilic microorganisms have several operational advantages as a production host over mesophilic organisms, such as low cooling costs, reduced contamination risks and a process temperature matching that of commercial hydrolytic enzymes, enabling simultaneous saccharification and fermentation at higher efficiencies and with less enzymes. However, genetic tools for biotechnologically relevant thermophiles are still in their infancy. In this study we developed a markerless gene deletion method for the thermophile Bacillus smithii and we report the first metabolic engineering of this species as a potential platform organism. RESULTS: Clean deletions of the ldhL gene were made in two B. smithii strains (DSM 4216(T) and compost isolate ET 138) by homologous recombination. Whereas both wild-type strains produced mainly L-lactate, deletion of the ldhL gene blocked L-lactate production and caused impaired anaerobic growth and acid production. To facilitate the mutagenesis process, we established a counter-selection system for efficient plasmid removal based on lacZ-mediated X-gal toxicity. This counter selection system was applied to construct a sporulation-deficient B. smithii DeltaldhL DeltasigF mutant strain. Next, we demonstrated that the system can be used repetitively by creating B. smithii triple mutant strain ET 138 DeltaldhL DeltasigF DeltapdhA, from which also the gene encoding the alpha-subunit of the E1 component of the pyruvate dehydrogenase complex is deleted. This triple mutant strain produced no acetate and is auxotrophic for acetate, indicating that pyruvate dehydrogenase is the major route from pyruvate to acetyl-CoA. CONCLUSIONS: In this study, we developed a markerless gene deletion method including a counter-selection system for thermophilic B. smithii, constituting the first report of metabolic engineering in this species. The described markerless gene deletion system paves the way for more extensive metabolic engineering of B. smithii. This enables the development of this species into a platform organism and provides tools for studying its metabolism, which appears to be different from its close relatives such as B. coagulans and other bacilli. PMID- 26148487 TI - Electrically induced ambipolar spin vanishments in carbon nanotubes. AB - Carbon nanotubes (CNTs) exhibit various excellent properties, such as ballistic transport. However, their electrically induced charge carriers and the relation between their spin states and the ballistic transport have not yet been microscopically investigated because of experimental difficulties. Here we show an electron spin resonance (ESR) study of semiconducting single-walled CNT thin films to investigate their spin states and electrically induced charge carriers using transistor structures under device operation. The field-induced ESR technique is suitable for microscopic investigation because it can directly observe spins in the CNTs. We observed a clear correlation between the ESR decrease and the current increase under high charge density conditions, which directly demonstrated electrically induced ambipolar spin vanishments in the CNTs. The result provides a first clear evidence of antimagnetic interactions between spins of electrically induced charge carriers and vacancies in the CNTs. The ambipolar spin vanishments would contribute the improvement of transport properties of CNTs because of greatly reduced carrier scatterings. PMID- 26148488 TI - Survival in patchy landscapes: the interplay between dispersal, habitat loss and fragmentation. AB - Habitat loss and fragmentation are important factors determining animal population dynamics and spatial distribution. Such landscape changes can lead to the deleterious impact of a significant drop in the number of species, caused by critically reduced survival rates for organisms. In order to obtain a deeper understanding of the threeway interplay between habitat loss, fragmentation and survival rates, we propose here a spatially explicit multi-scaled movement model of individuals that search for habitat. By considering basic ecological processes, such as predation, starvation (outside the habitat area), and competition, together with dispersal movement as a link among habitat areas, we show that a higher survival rate is achieved in instances with a lower number of patches of larger areas. Our results demonstrate how movement may counterbalance the effects of habitat loss and fragmentation in altered landscapes. In particular, they have important implications for conservation planning and ecosystem management, including the design of specific features of conservation areas in order to enhance landscape connectivity and population viability. PMID- 26148489 TI - Do Negative Changes in Worldview Mediate Links Between Mass Trauma and Reckless Behavior? A Longitudinal Exploratory Study. AB - Trauma exposure heightens the risk of reckless behavior and is now included in DSM-5 posttraumatic stress disorder symptomatology. Individuals exposed to trauma may be likely to engage in reckless behavior because of negative changes in their worldview (referred to as disrupted worldview). The current study investigates the relationship between DSM-IV posttraumatic stress symptoms, disrupted worldview, and increased reckless behavior among 1145 students exposed to mass violence. Total posttraumatic stress symptomatology was associated with increased and persistent reckless behavior, supporting DSM-5 diagnostic inclusion. Although posttraumatic stress symptomatology predicted reckless behavior among those with varying levels of posttraumatic symptomatology, individuals with high symptomatology reported significantly higher recklessness. Disrupted worldview mediated the relationship between posttraumatic symptomatology and reckless behavior among individuals with high symptomatology, while only partially mediating the relationship among those with low symptomatology. These findings provide support for worldview disruptions as a mechanism by which prolonged reckless behavior may be manifested. PMID- 26148490 TI - Clinical Evaluation of Sinonasal Lesions in Patients With Immunoglobulin G4 Related Disease. AB - OBJECTIVES: Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease entity characterized by elevated serum IgG4 and extensive IgG4-positive plasma cell infiltration of various organs. Patients with IgG4-RD show nasal manifestations with chronic rhinosinusitis. The objective of this study was to evaluate the clinical characteristics of sinonasal lesions in patients with IgG4 RD. METHODS: We evaluated radiological findings of sinonasal lesions in 79 patients with IgG4-RD who were divided into 3 groups according to severity. We also compared serological findings, including serum IgG4 and IgE levels, and eosinophil counts. RESULTS: Rhinosinusitis was found in 41 patients (51.9%). Although there were no significant differences in the serum IgG4 and IgE levels of the groups, there was a significant increase in eosinophil counts (445 +/- 311.9/mm3) in Group C. Furthermore, 14 of the 41 patients with rhinosinusitis (34.1%) showed improvement after prednisolone administration. Patients with IgG4 RD and serum eosinophilia tend to also have sinonasal lesions. CONCLUSIONS: Rhinosinusitis is common in patients with IgG4-RD, and its pathogenesis can be similar to eosinophilic chronic rhinosinusitis. PMID- 26148491 TI - Energy Flux in the Cochlea: Evidence Against Power Amplification of the Traveling Wave. AB - Traveling waves in the inner ear exhibit an amplitude peak that shifts with frequency. The peaking is commonly believed to rely on motile processes that amplify the wave by inserting energy. We recorded the vibrations at adjacent positions on the basilar membrane in sensitive gerbil cochleae and tested the putative power amplification in two ways. First, we determined the energy flux of the traveling wave at its peak and compared it to the acoustic power entering the ear, thereby obtaining the net cochlear power gain. For soft sounds, the energy flux at the peak was 1 +/- 0.6 dB less than the middle ear input power. For more intense sounds, increasingly smaller fractions of the acoustic power actually reached the peak region. Thus, we found no net power amplification of soft sounds and a strong net attenuation of intense sounds. Second, we analyzed local wave propagation on the basilar membrane. We found that the waves slowed down abruptly when approaching their peak, causing an energy densification that quantitatively matched the amplitude peaking, similar to the growth of sea waves approaching the beach. Thus, we found no local power amplification of soft sounds and strong local attenuation of intense sounds. The most parsimonious interpretation of these findings is that cochlear sensitivity is not realized by amplifying acoustic energy, but by spatially focusing it, and that dynamic compression is realized by adjusting the amount of dissipation to sound intensity. PMID- 26148493 TI - An unusual pharyngeal mass. AB - A 37-year-old man presented with an abnormal pharyngeal sensation. Nasendoscopy demonstrated a mass projecting from the left pharyngeal wall, which could be pushed medially with external pressure. A CT scan demonstrated a fracture of the hyoid. On further questioning, the patient stated that he practised Jujitsu, a sport involving various strangling manoeuvres. He underwent a pharyngoscopy and out-fracturing of the hyoid, resulting in complete resolution of his symptoms. Hyoid fractures are uncommon and can be difficult to identify clinically, but the serious nature of associated complications highlights the importance of making the diagnosis. PMID- 26148492 TI - Multiple interval QTL mapping and searching for PSTOL1 homologs associated with root morphology, biomass accumulation and phosphorus content in maize seedlings under low-P. AB - BACKGROUND: Modifications in root morphology are important strategies to maximize soil exploitation under phosphorus starvation in plants. Here, we used two multiple interval models to map QTLs related to root traits, biomass accumulation and P content in a maize RIL population cultivated in nutrient solution. In addition, we searched for putative maize homologs to PSTOL1, a gene responsible to enhance early root growth, P uptake and grain yield in rice and sorghum. RESULTS: Based on path analysis, root surface area was the root morphology component that most strongly contributed to total dry weight and to P content in maize seedling under low-P availability. Multiple interval mapping models for single (MIM) and multiple traits (MT-MIM) were combined and revealed 13 genomic regions significantly associated with the target traits in a complementary way. The phenotypic variances explained by all QTLs and their epistatic interactions using MT-MIM (23.4 to 35.5 %) were higher than in previous studies, and presented superior statistical power. Some of these QTLs were coincident with QTLs for root morphology traits and grain yield previously mapped, whereas others harbored ZmPSTOL candidate genes, which shared more than 55 % of amino acid sequence identity and a conserved serine/threonine kinase domain with OsPSTOL1. Additionally, four ZmPSTOL candidate genes co-localized with QTLs for root morphology, biomass accumulation and/or P content were preferentially expressed in roots of the parental lines that contributed the alleles enhancing the respective phenotypes. CONCLUSIONS: QTL mapping strategies adopted in this study revealed complementary results for single and multiple traits with high accuracy. Some QTLs, mainly the ones that were also associated with yield performance in other studies, can be good targets for marker-assisted selection to improve P-use efficiency in maize. Based on the co-localization with QTLs, the protein domain conservation and the coincidence of gene expression, we selected novel maize genes as putative homologs to PSTOL1 that will require further validation studies. PMID- 26148494 TI - A cardiac haemangioma: the contribution of myocardial contrast echocardiography in the diagnosis. AB - Cardiac haemangiomas are extremely rare and account for approximately 2% of all primary resected cardiac tumours. They can occur in any chamber and at any level, from pericardium to endocardium. Myocardial contrast echocardiography is an imaging tool for the assessment of myocardial microcirculation. It can also be used for the evaluation of the relative perfusion of a cardiac mass. We report a case of a 17-year-old male patient who was referred for cardiological evaluation because of a 2/6 systolic murmur. Transthoracic echocardiography revealed a mass in the left ventricle. Using myocardial perfusion contrast echocardiography, the mass was rapidly filled with contrast greater than the adjacent myocardium, suggesting intense vascularisation. The mass was successfully resected and the subsequent histopathological examination showed a cardiac haemangioma. Therefore, myocardial perfusion contrast echocardiography appears to be a valuable diagnostic tool in differentiating the different types of cardiac masses. PMID- 26148495 TI - Double jeopardy: two major complications of a myocardial infarction in one patient. AB - A 62-year-old woman with no cardiac history was admitted to the hospital with an ambulant inferoposterolateral myocardial infarction. She experienced two major complications, namely, a free-wall rupture of the infarcted area, on which a bovine pericardial patch was glued surgically, and, a few days later, a posteromedial papillary muscle rupture, for which a mitral valve replacement was performed. She survived both complications and is now rehabilitating at home. PMID- 26148496 TI - Factors associated with uptake of influenza vaccine in people aged 50 to 64 years in Hong Kong: a case-control study. AB - BACKGROUND: In Hong Kong, people aged 50-64 years were added as a recommended priority group (recommended group) for influenza vaccination by the Department of Health (DH) starting from 2011/12 onwards. The coverage rate of influenza vaccination for this age group was suboptimal at 8.5 % in 2012/13. This study investigates the factors associated with the uptake of influenza vaccination among adults in Hong Kong aged 50-64 years. METHODS: A case-control study was conducted in communities by street intercept interviews from 17 July to 15 August 2013. Cases were adults aged 50-64 years who had received the influenza vaccine in 2011/12 or 2012/13, while controls were the same as the cases, except they had not received the influenza vaccine in 2011/12 or 2012/13. Multiple logistic regression analysis was performed on the data to explore the associations between vaccination status and the variables. RESULTS: Six hundred and four respondents in total were interviewed and included in the analysis. There were 193 cases (vaccinated) and 411 controls (non-vaccinated), with a case-to-control ratio of 1:2.1. The following were strongly associated with vaccination compared to other factors: 'eligible for free government vaccine' (OR6.38, 95 % CI, 3.43-11.87, p < 0.001); 'willing to receive flu vaccination for free' (OR4.84, 95 % CI, 2.13 11.03, p < 0.001); 'perceived having severe or moderate symptoms when contracting flu' (OR2.90, 95 % CI, 1.21-6.97, p = 0.02), and 'convenient to reach a vaccination location' (OR2.87, 95 % CI, 1.06-7.74, p = 0.04). The majority of the cases (80.8 %) and controls (93.9 %) were not aware that they belonged to a recommended group for influenza vaccination and most (>80 %) were willing to be vaccinated if it was free. CONCLUSIONS: Factors related to free and convenient vaccination, the perception of the severity of symptoms when contracting influenza had a comparatively strong association with influenza vaccination uptake amongst 50-64 year olds, compared to other factors. PMID- 26148497 TI - Multiplex PCR for rapid diagnosis and differentiation of pox and pox-like diseases in dromedary Camels. AB - BACKGROUND: Pox and pox-like diseases of camels are a group of exanthematous skin conditions that have become increasingly important economically. Three distinct viruses may cause them: camelpox virus (CMLV), camel parapox virus (CPPV) and camelus dromedary papilloma virus (CdPV). These diseases are often difficult to differentiate based on clinical presentation in disease outbreaks. Molecular methods such as PCR targeting species-specific genes have been developed and used to identify these diseases, but not simultaneously in a single tube. Recently, multiplex PCR has gained reputation as a convenient diagnostic method with cost and timesaving benefits. METHODS AND RESULTS: In the present communication, we describe the development, optimization and validation of a multiplex PCR assay able to detect simultaneously the genome of the three viruses in one single test allowing for rapid and efficient molecular diagnosis. The assay was developed based on the evaluation and combination of published and new primer sets and was validated with viral genomic DNA extracted from known virus strains (n = 14) and DNA extracted from homogenized clinical skin specimens (n = 86). The assay detects correctly the target pathogens by amplification of targeted genes, even in case of co-infection. The method showed high sensitivity, and the specificity was confirmed by PCR-product sequencing. CONCLUSION: This assay provide rapid, sensitive and specific method for identifying three important viruses in specimens collected from dromedary camels with varying clinical presentations. PMID- 26148498 TI - Conditional Gene Expression/Deletion Systems for Marchantia polymorpha Using its Own Heat-Shock Promoter and Cre/loxP-Mediated Site-Specific Recombination. AB - The liverwort Marchantia polymorpha is an emerging model plant suitable for addressing, using genetic approaches, various evolutionary questions in the land plant lineage. Haploid dominancy in its life cycle facilitates genetic analyses, but conversely limits the ability to isolate mutants of essential genes. To overcome this issue and to be employed in cell lineage, mosaic and cell autonomy analyses, we developed a system that allows conditional gene expression and deletion using a promoter of a heat-shock protein (HSP) gene and the Cre/loxP site-specific recombination system. Because the widely used promoter of the Arabidopsis HSP18.2 gene did not operate in M. polymorpha, we identified a promoter of an endogenous HSP gene, MpHSP17.8A1, which exhibited a highly inducible transient expression level upon heat shock with a low basal activity level. Reporter genes fused to this promoter were induced globally in thalli under whole-plant heat treatment and also locally using a laser-assisted targeted heating technique. By expressing Cre fused to the glucocorticoid receptor under the control of the MpHSP17.8A1 promoter, a low background, sufficiently inducible control for loxP-mediated recombination could be achieved in M. polymorpha. Based on these findings, we developed a Gateway technology-based binary vector for the conditional induction of gene deletions. PMID- 26148499 TI - CrEdit: CRISPR mediated multi-loci gene integration in Saccharomyces cerevisiae. AB - BACKGROUND: One of the bottlenecks in production of biochemicals and pharmaceuticals in Saccharomyces cerevisiae is stable and homogeneous expression of pathway genes. Integration of genes into the genome of the production organism is often a preferred option when compared to expression from episomal vectors. Existing approaches for achieving stable simultaneous genome integrations of multiple DNA fragments often result in relatively low integration efficiencies and furthermore rely on the use of selection markers. RESULTS: Here, we have developed a novel method, CrEdit (CRISPR/Cas9 mediated genome Editing), which utilizes targeted double strand breaks caused by CRISPR/Cas9 to significantly increase the efficiency of homologous integration in order to edit and manipulate genomic DNA. Using CrEdit, the efficiency and locus specificity of targeted genome integrations reach close to 100% for single gene integration using short homology arms down to 60 base pairs both with and without selection. This enables direct and cost efficient inclusion of homology arms in PCR primers. As a proof of concept, a non-native beta-carotene pathway was reconstructed in S. cerevisiae by simultaneous integration of three pathway genes into individual intergenic genomic sites. Using longer homology arms, we demonstrate highly efficient and locus-specific genome integration even without selection with up to 84% correct clones for simultaneous integration of three gene expression cassettes. CONCLUSIONS: The CrEdit approach enables fast and cost effective genome integration for engineering of S. cerevisiae. Since the choice of the targeting sites is flexible, CrEdit is a powerful tool for diverse genome engineering applications. PMID- 26148500 TI - MicroRNA nomenclature and the need for a revised naming prescription. AB - A central environment and interface for microRNA (miRNA) registry and repository and a general standardized framework for their systematic annotation was established over a decade ago. However, the numbers of experimentally and computationally identified miRNAs are swiftly accumulating, and new aspects of miRNA-mediated gene regulation are being revealed. Currently, it is of great significance that the annotation framework should be redefined to include newly discovered miRNA species such as the variants of mature miRNAs (isomiRNAs), and organellar miRNAs: cipomiRNAs and mitomiRNAs. It is also of great importance that key terminology referring to the novelty, evolutionary history or biogenesis of miRNAs, as well as the confidence of their identification are standardized in the literature and disseminated in a central miRNA registry. Here, we review the status of miRNA nomenclature, curation and critical points of need for a revision of miRNA nomenclature and terminology. PMID- 26148501 TI - Knowledge, attitudes and use of labour analgesia among women at a low-income country antenatal clinic. AB - BACKGROUND: Childbirth is one of the most painful experiences of a woman's life. Authorities in the fields of obstetrics and anaesthesia encourage use of labour analgesia. Unlike in high-income countries, pain relief in labour in Africa is not a well established service, especially in the low-income countries like Uganda. Little is known about whether parturients would be amenable to labour analgesia. We sought to determine knowledge, attitudes and use of labour analgesia among women attending the antenatal clinic at Mulago National Referral Hospital. METHODS: Upon obtaining institutional approval, we conducted a cross sectional descriptive study. Women were requested to complete the researcher administered survey following informed consent. The study was conducted in the general antenatal clinic at the Mulago National Referral Hospital. RESULTS: Of 1293 participants interviewed, only 7 % of the participants had knowledge of labour analgesia. Of the multiparous mothers 87.9 % did not have labour analgesia in their previous deliveries, although 79.2 % of them had delivered in a national referral hospital. The commonest reason for refusal of labour analgesia was to experience natural childbirth. 87.7 % of the participants wanted labour analgesia for their next delivery. CONCLUSION: There is a wide gap between the desire for labour analgesia and its availability. Obstetricians and anaesthesiologists have a role to educate the women, and to provide this much desired service. PMID- 26148502 TI - Identification of Hop stunt viroid infecting Citrus limon in China using small RNAs deep sequencing approach. AB - BACKGROUND: The advent of next generation sequencing technology has allowed for significant advances in plant virus discovery, particularly for identification of covert viruses and previously undescribed viruses. The Citrus limon Burm. f. (C. limon) is a small evergreen tree native to Asia, and . China is the world's top lemon-producing nation. FINDINGS: In this work, lemon samples were collected from southwestern of China, where an unknown disease outbreak had caused huge losses in the lemon production industry. Using high-throughput pyrosequencing and the assembly of small RNAs, we showed that the Hop stunt viroid (HSVd) was present in C. limon leaf sample. The majority of it is a main lemon producing agricultural cultivarHop stunt viroid derived siRNAs (HSVd-siRNAs) in C. limon were 21 nucleotides in length, and nearly equal amount of HSVd-siRNAs originated from the plus-genomic RNA strand as from the complementary strand. A bias of HSVd-siRNAs toward sequences beginning with a 5'-Guanine was observed. Furthermore, hotspot analysis showed that a large amount of HSVd-siRNAs derived from the central and variant domains of the HSVd genome. CONCLUSIONS: Our results suggest that C. limon could set up a small RNA-mediated gene silencing response to Hop stunt viroid, Interestingly, based on bioinformatics analysis, our results also suggest that the large amounts of HSVd-siRNAs from central and variant domains might be involved in interference with host gene expression and affect symptom development. PMID- 26148504 TI - Cyclic fatigue analysis of Reciproc R25(r) instruments with different kinematics. AB - This study aimed to compare the cyclic fatigue resistance of Reciproc(r) instruments when used with different kinematics (150 degrees counterclockwise (CCW)-30 degrees clockwise (CW), 270 degrees CCW-30 degrees CW, 360 degrees CCW-30 degrees CW and continuous rotation). Various kinematics were tested in steel canals with a 3 mm radius and a 60 degrees angle of curvature as follows (n = 20): 150 degrees CCW-30 degrees CW, 270 degrees CCW-30 degrees CW, 360 degrees CCW-30 degrees CW and 360 degrees CCW (rotary motion). Reciproc R25(r) instruments were used until fracture occurred. The time to fracture was recorded in seconds. The data were statistically analysed using a one-way analysis of variance and Tukey's post-hoc tests (P = .05). The cyclic fatigue resistance of Reciproc R25(r) instruments used with various kinematics in decreasing order was as follows: 150 degrees CCW-30 degrees CW > 270 degrees CCW-30 degrees CW = 360 degrees CCW-30 degrees CW > 360 degrees CCW rotary motion. The 150 degrees CCW-30 degrees CW reciprocating motion had the best performance in time to fracture. All reciprocating motions (150 degrees CCW-30 degrees CW, 270 degrees CCW-30 degrees CW and 360 degrees CCW-30 degrees CW) resulted in a longer mean duration to failure compared with the 360 degrees CCW rotary motion. PMID- 26148503 TI - Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients. AB - BACKGROUND: Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. AIM: To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. METHODS: Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. RESULTS: A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. CONCLUSIONS: Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent. PMID- 26148505 TI - MECP2, a gene associated with Rett syndrome in humans, shows conserved coding regions, independent Alu insertions, and a novel transcript across primate evolution. AB - BACKGROUND: The methyl-CpG Binding Protein two gene (MECP2) encodes a multifunctional protein comprising two isoforms involved in nuclear organization and regulation of splicing and mRNA template activity. This gene is normally expressed in all tissues, with a higher expression level in the brain during neuronal maturation. Loss of MECP2 function is the primary cause of Rett syndrome (RTT) in humans, a dominant, X-linked disorder dramatically affecting neural and motor development. RESULTS: We investigated the molecular evolution of MECP2 in several primate taxa including 36 species in 16 genera of neotropical (platyrrhine) primates. The coding region of the MECP2_e2 isoform showed a high level of evolutionary conservation among humans and other primates, with amino acid substitutions in 14 codons and one in-frame insertion of a single serine codon, between codons 357 and 358, in Ateles paniscus. Most substitutions occurred in noncritical regions of MECP2 and the majority of the algorithms used for analyzing selection did not provide evidence of positive selection. Conversely, we found 48 sites under negative selection in different regions, 23 of which were consistently found by three different algorithms. Similar to an inverted Alu insert found previously in a lesser ape at a parallel location, one Alu insertion of approximately 300 bp in Cebus and Sapajus was found in intron 3. Phylogenetic reconstruction of the intron 3 data provided a topology that was coincident with the consensus arrangement of the primate taxa. RNAseq data in the neotropical primate Callimico goeldii revealed a novel transcript consisting of a noncontinuous region of the human-homologous intron 2 in this species; this transcript accounted for two putative polypeptides. CONCLUSIONS: Despite the remarkable evolutionary conservation of MECP2, one in-frame codon insertion was observed in A. paniscus, and one region of intron 3 was affected by a trans specific Alu retrotransposition in two neotropical primate genera. Moreover, identification of novel MECP2 transcripts in Callimico suggests that part of a homologous human intronic region might be expressed, and that the potential open reading frame in this region might be a subject of interest in RTT patients who carry an apparently normal MECP2 sequence. PMID- 26148506 TI - Quantifying the healthcare costs of treating severely bleeding major trauma patients: a national study for England. AB - INTRODUCTION: Severely bleeding trauma patients are a small proportion of the major trauma population but account for 40% of all trauma deaths. Healthcare resource use and costs are likely to be substantial but have not been fully quantified. Knowledge of costs is essential for developing targeted cost reduction strategies, informing health policy, and ensuring the cost effectiveness of interventions. METHODS: In collaboration with the Trauma Audit Research Network (TARN) detailed patient-level data on in-hospital resource use, extended care at hospital discharge, and readmissions up to 12 months post-injury were collected on 441 consecutive adult major trauma patients with severe bleeding presenting at 22 hospitals (21 in England and one in Wales). Resource use data were costed using national unit costs and mean costs estimated for the cohort and for clinically relevant subgroups. Using nationally available data on trauma presentations in England, patient-level cost estimates were up-scaled to a national level. RESULTS: The mean (95% confidence interval) total cost of initial hospital inpatient care was L19,770 (L18,177 to L21,364) per patient, of which 62% was attributable to ventilation, intensive care, and ward stays, 16% to surgery, and 12% to blood component transfusion. Nursing home and rehabilitation unit care and re-admissions to hospital increased the cost to L20,591 (L18,924 to L22,257). Costs were significantly higher for more severely injured trauma patients (Injury Severity Score >=15) and those with blunt injuries. Cost estimates for England were L148,300,000, with over a third of this cost attributable to patients aged 65 years and over. CONCLUSIONS: Severely bleeding major trauma patients are a high cost subgroup of all major trauma patients, and the cost burden is projected to rise further as a consequence of an aging population and as evidence continues to emerge on the benefits of early and simultaneous administration of blood products in pre-specified ratios. The findings from this study provide a previously unreported baseline from which the potential impact of changes to service provision and/or treatment practice can begin to be evaluated. Further studies are still required to determine the full costs of post-discharge care requirements, which are also likely to be substantial. PMID- 26148507 TI - Luteal phase support for assisted reproduction cycles. AB - BACKGROUND: Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin(hCG) produced by the corpus luteum. This occurs in the luteal phase of the menstrual cycle. In assisted reproduction techniques(ART), progesterone and/or hCG levels are low, so the luteal phase is supported with progesterone, hCG or gonadotropin-releasing hormone (GnRH) agonists to improve implantation and pregnancy rates. OBJECTIVES: To determine the relative effectiveness and safety of methods of luteal phase support provided to subfertile women undergoing assisted reproduction. SEARCH METHODS: We searched databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and trial registers. We conducted searches in November 2014, and further searches on 4 August 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) of luteal phase support using progesterone, hCG or GnRH agonist supplementation in ART cycles. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials, extracted data and assessed risk of bias. We calculated odds ratios (ORs) and 95%confidence intervals (CIs) for each comparison and combined data when appropriate using a fixed-effect model. Our primary out come was live birth or ongoing pregnancy. The overall quality of the evidence was assessed using GRADE methods. MAIN RESULTS: Ninety-four women RCTs (26,198 women) were included. Most studies had unclear or high risk of bias in most domains. The main limitations in the evidence were poor reporting of study methods and imprecision due to small sample sizes.1. hCG vs placebo/no treatment (five RCTs, 746 women)There was no evidence of differences between groups in live birth or ongoing pregnancy (OR 1.67, 95% CI 0.90 to 3.12, three RCTs,527 women, I2 = 24%, very low-quality evidence, but I2 of 61% was found for the subgroup of ongoing pregnancy) with a random effects model. hCG increased the risk of ovarian hyperstimulation syndrome (OHSS) (1 RCT, OR 4.28, 95% CI 1.91 to 9.6, low quality evidence).2. Progesterone vs placebo/no treatment (eight RCTs, 875 women)Evidence suggests a higher rate of live birth or ongoing pregnancy in the progesterone group (OR 1.77, 95% CI 1.09 to 2.86, five RCTs, 642 women, I2 = 35%, very low-quality evidence). OHSS was not reported.3. Progesterone vs hCG regimens (16 RCTs, 2162 women)hCG regimens included comparisons of progesterone versus hCG and progesterone versus progesterone + hCG. No evidence showed differences between groups in live birth or ongoing pregnancy (OR 0.95, 95% CI 0.65 to 1.38, five RCTs, 833 women, I2 = 0%, low quality evidence) or in the risk of OHSS (four RCTs, 615 women, progesterone vs hCG OR 0.54, 95% CI 0.22 to 1.34; four RCTs,678 women; progesterone vs progesterone plus hCG, OR 0.34, 95% CI 0.09 to 1.26, low-quality evidence).4. Progesterone vs progesterone with oestrogen (16 RCTs, 2577 women)No evidence was found of differences between groups in live birth or ongoing pregnancy (OR 1.12, 95% CI 0.91 to 1.38, nine RCTs,1651 women, I2 = 0%, low quality evidence) or OHSS (OR 0.56, 95% CI 0.2 to 1.63, two RCTs, 461 women, I2 = 0%, low-quality evidence).5. Progesterone vs progesterone + GnRH agonist (seven RCTs, 1708 women)Live birth or ongoing pregnancy rates were lower in the progesterone-only group and increased in women who received progester one and one or more GnRH agonist doses (OR 0.62, 95% CI 0.48 to 0.81, nine RCTs, 2861 women, I2 = 55%, random effects, low quality evidence). Statistical heterogeneity for this comparison was high because of unexplained variation in the effect size, but the direction of effect was consistent across studies. OHSS was reported in one study only (OR 1.00, 95% CI 0.33 to 3.01, 1 RCT, 300 women, very low quality evidence).6. Progesterone regimens (45 RCTs, 13,814 women)The included studies reported nine different comparisons between progesterone regimens. Findings for live birth or ongoing pregnancy were as follows: intramuscular (IM) versus oral: OR 0.71, 95% CI 0.14 to 3.66 (one RCT, 40 women, very low-quality evidence);IM versus vaginal/rectal: OR 1.24, 95% CI 1.03 to 1.5 (seven RCTs, 2309 women, I2 = 71%, very low-quality evidence); vaginal/rectal versus oral: OR 1.19, 95% CI 0.83 to 1.69 (four RCTs, 857 women, I2 = 32%, low-quality evidence); low-dose versus high-dose vaginal: OR 0.97, 95% CI 0.84 to 1.11 (five RCTs, 3720 women, I2 = 0%, moderate-quality evidence); short versus long protocol:OR 1.04, 95% CI 0.79 to 1.36 (five RCTs, 1205 women, I2 = 0%, low-quality evidence); micronised versus synthetic: OR 0.9, 95%CI 0.53 to 1.55 (two RCTs, 470 women, I2 = 0%, low-quality evidence); vaginal ring versus gel: OR 1.09, 95% CI 0.88 to 1.36 (oneRCT, 1271 women, low-quality evidence); subcutaneous versus vaginal gel: OR 0.92, 95% CI 0.74 to 1.14 (two RCTs, 1465 women,I2 = 0%, low-quality evidence); and vaginal versus rectal: OR 1.28, 95% CI 0.64 to 2.54 (one RCT, 147 women, very low-quality evidence). OHSS rates were reported for only two of these comparisons: IM versus oral, and low versus high-dose vaginal. No evidence showed a difference between groups.7. Progesterone and oestrogen regimens (two RCTs, 1195 women)The included studies compared two different oestrogen protocols. No evidence was found to suggest differences in live birth or ongoing pregnancy rates between a short and a long protocol (OR 1.08, 95% CI 0.81 to 1.43, one RCT, 910 women, low-quality evidence) or between a low dose and a high dose of oestrogen (OR 0.65, 95% CI 0.37 to 1.13, one RCT, 285 women, very low-quality evidence).Neither study reported OHSS. AUTHORS' CONCLUSIONS: Both progesterone and hCG during the luteal phase are associated with higher rates of live birth or ongoing pregnancy than placebo.The addition of GnRHa to progesterone is associated with an improvement in pregnancy outcomes. OHSS rates are increased with hCG compared to placebo (only study only). The addition of oestrogen does not seem to improve outcomes. The route of progester one administration is not associated with an improvement in outcomes. PMID- 26148508 TI - Neither endothelial function nor carotid artery intima-media thickness predicts coronary computed tomography angiography plaque burden in clinically healthy subjects: a cross-sectional study. AB - BACKGROUND: Cardiovascular risk assessment is usually based on traditional risk factors and risk assessment algorithms. However, a number of risk markers that might provide additional predictive power have been identified. Endothelial function determined by digital reactive hyperemia peripheral arterial tonometry (RH-PAT) and carotid artery intima-media thickness (IMT) have both been proposed as surrogate markers for coronary artery disease (CAD). We aimed to examine the ability of RH-PAT and IMT to predict coronary computed tomography angiography (CTA) plaque burden in clinically healthy subjects. METHODS: Fifty-eight clinically healthy volunteers (50-73 years old) underwent testing for RH-PAT and IMT as well as coronary CTA, including coronary artery calcium (CAC) scoring. Coronary CTA was analyzed with respect to any atheromatous plaques, stenotic as well as non-stenotic. The Mann-Whitney U-test was used to compare the groups with and without CAD and the Spearman test was used to test for correlation between variables. RESULTS: Twenty-five (43 %) subjects had normal coronary arteries, without any signs of atherosclerosis. The median (range) number of diseased segments was 1 (0-10), RH-PAT index 2.2 (1.4-4.9), IMT 0.70 (0.49-0.99) mm and CAC 4 (0-1882). There was no association between presence or extent of CAD and RH PAT index (Spearman correlation coefficient rs = 0.13) or IMT (rs = 0.098). As expected, CAC was strongly correlated to presence and extent of CAD by coronary CTA (rs =0.86; p < 0.0001). CONCLUSIONS: Neither evaluation of endothelial function by RH-PAT nor assessment of carotid artery IMT can reliably be used to predict coronary CTA plaque burden in clinically healthy subjects. PMID- 26148509 TI - DAXX modulates human papillomavirus early gene expression and genome replication in U2OS cells. AB - BACKGROUND: The human papillomavirus (HPV) genomes can replicate, and are maintained as autonomously replicating extrachromosomal plasmids in human U2OS cells. Previous studies have shown that HPV genomes are transcriptionally active in U2OS cells and can express the viral early proteins required for initiation and establishment of HPV replication. In the present work, we have examined the involvement of cellular DAXX protein in HPV replication in U2OS cells. METHODS: We have used indirect immunofluorescence and FISH analysis in order to study HPV replication compartments in U2OS cells. In addition, we have used siRNA knock down for examining the effect of the DAXX protein on HPV replication and transcription in U2OS cells. RESULTS: We show that a portion of HPV replication foci are partially co-localized with components of ND10, cellular DAXX and PML proteins. In addition, we demonstrate that the knock-down of the cellular DAXX protein modulates the HPV genome replication and transcription in U2OS cells- papillomavirus replication is reduced in the absence of this component of ND10. CONCLUSIONS: The DAXX protein modulates the early gene expression and the transient replication of HPV genomes in U2OS cells. PMID- 26148510 TI - Recovery from post-traumatic stress disorder after a flood in China: a 13-year follow-up and its prediction by degree of collective action. AB - BACKGROUND: Victims exposed to serious traumatic experiences may develop post traumatic stress disorder (PTSD) and suffer this mental health problem for a long time. Different types of trauma displayed a chronicity rate of PTSD within the range of 6.3-68.9 %. As one of the most common and severe natural disasters, the natural progression of flood related PTSD has not been revealed. The aim of this study was to estimate the chronicity rate and identify the prognostic factors of PTSD in flood victims. METHODS: Flood victims, who were over the age of 16 and diagnosed with PTSD in 2000 in Huarong, Ziyang, and Anxiang counties of Hunan province, China, were enrolled in this survey. Current probable PTSD was analyzed using the PTSD Checklist-Civilian version. Data were collected in face-to-face interviews and analyzed using univariate analysis and multiple logistic regression models. RESULTS: The rate of current probable PTSD was 15.4 %. The current occurrences of re-experiencing, avoidance/numbing, and hyper-arousal symptom groups were 69.3 %, 17.2 %, and 50.2 %, respectively. Significant prognostic factors for current probable PTSD were flood-related stressors (e.g., life-threatening experiences, extreme physical adversity, and extreme psychological adversity) and frequency of general collective action. The relationships still existed when taking the fluctuation of frequency of general collective action into consideration. Gender and education level showed no influence on the recovery from PTSD. The impact of age in this study was inconsistent; in the 2000 model, around 2006 model, around 2013 model, and all FGCA model, older age was positive prognosis factor for PTSD; in the univariate analysis and fluctuation model, age showed no influence on the recovery from PTSD. CONCLUSIONS: Our findings indicated that PTSD can persist 13 years after a flood. Demographic characteristics (e.g., age, gender, and education level) seem to have no influence on the recovery from PTSD. Trauma-related stressors and social participation are important predictors for remission from chronic PTSD. PMID- 26148511 TI - Modulation of flagellum attachment zone protein FLAM3 and regulation of the cell shape in Trypanosoma brucei life cycle transitions. AB - The cell shape of Trypanosoma brucei is influenced by flagellum-to-cell-body attachment through a specialised structure - the flagellum attachment zone (FAZ). T. brucei exhibits numerous morphological forms during its life cycle and, at each stage, the FAZ length varies. We have analysed FLAM3, a large protein that localises to the FAZ region within the old and new flagellum. Ablation of FLAM3 expression causes a reduction in FAZ length; however, this has remarkably different consequences in the tsetse procyclic form versus the mammalian bloodstream form. In procyclic form cells FLAM3 RNAi results in the transition to an epimastigote-like shape, whereas in bloodstream form cells a severe cytokinesis defect associated with flagellum detachment is observed. Moreover, we demonstrate that the amount of FLAM3 and its localisation is dependent on ClpGM6 expression and vice versa. This evidence demonstrates that FAZ is a key regulator of trypanosome shape, with experimental perturbations being life cycle form dependent. An evolutionary cell biology explanation suggests that these differences are a reflection of the division process, the cytoskeleton and intrinsic structural plasticity of particular life cycle forms. PMID- 26148513 TI - Dissecting the roles of human BUB1 in the spindle assembly checkpoint. AB - Mitotic chromosome segregation is initiated by the anaphase promoting complex/cyclosome (APC/C) and its co-activator CDC20 (forming APC/C(CDC20)). APC/C(CDC20) is inhibited by the spindle assembly checkpoint (SAC) when chromosomes have not attached to spindle microtubules. Unattached kinetochores catalyze the formation of a diffusible APC/C(CDC20) inhibitor that comprises BUBR1 (also known as BUB1B), BUB3, MAD2 (also known as MAD2L1) and a second molecule of CDC20. Recruitment of these proteins to the kinetochore, as well as SAC activation, rely on the mitotic kinase BUB1, but the molecular mechanism by which BUB1 accomplishes this in human cells is unknown. We show that kinetochore recruitment of BUBR1 and BUB3 by BUB1 is dispensable for SAC activation. Unlike its yeast and nematode orthologs, human BUB1 does not associate stably with the MAD2 activator MAD1 (also known as MAD1L1) and, although required for accelerating the loading of MAD1 onto kinetochores, BUB1 is dispensable for the maintenance of steady-state levels of MAD1 there. Instead, we identify a 50-amino acid segment that harbors the recently reported ABBA motif close to a KEN box as being crucial for the role of BUB1 in SAC signaling. The presence of this segment correlates with SAC activity and efficient binding of CDC20 but not of MAD1 to kinetochores. PMID- 26148512 TI - Cezanne regulates E2F1-dependent HIF2alpha expression. AB - Mechanisms regulating protein degradation ensure the correct and timely expression of transcription factors such as hypoxia inducible factor (HIF). Under normal O2 tension, HIFalpha subunits are targeted for proteasomal degradation, mainly through vHL-dependent ubiquitylation. Deubiquitylases are responsible for reversing this process. Although the mechanism and regulation of HIFalpha by ubiquitin-dependent proteasomal degradation has been the object of many studies, little is known about the role of deubiquitylases. Here, we show that expression of HIF2alpha (encoded by EPAS1) is regulated by the deubiquitylase Cezanne (also known as OTUD7B) in an E2F1-dependent manner. Knockdown of Cezanne downregulates HIF2alpha mRNA, protein and activity independently of hypoxia and proteasomal degradation. Mechanistically, expression of the HIF2alpha gene is controlled directly by E2F1, and Cezanne regulates the stability of E2F1. Exogenous E2F1 can rescue HIF2alpha transcript and protein expression when Cezanne is depleted. Taken together, these data reveal a novel mechanism for the regulation of the expression of HIF2alpha, demonstrating that the HIF2alpha promoter is regulated by E2F1 directly and that Cezanne regulates HIF2alpha expression through control of E2F1 levels. Our results thus suggest that HIF2alpha is controlled transcriptionally in a cell-cycle-dependent manner and in response to oncogenic signalling. PMID- 26148514 TI - An unconventional calmodulin-anchoring site within the AB module of Kv7.2 channels. AB - Calmodulin (CaM) binding to the AB module is crucial for multiple mechanisms governing the function of Kv7.2 (also known as KCNQ2) K(+) channel subunits, which mediate one of the main components of the non-inactivating K(+) M-current, a key controller of neuronal excitability. Structural analysis indicates that the CaM N-lobe engages with helix B, whereas the C-lobe anchors to the IQ site within helix A. Here, we report the identification of a new site between helices A and B that assists in CaM binding whose sequence is reminiscent of the TW helix within the CaM C-lobe anchoring site of SK2 K(+) channels (also known as KCNN2). Mutations that disrupt CaM binding within the TW site, helix B or helix A yield functional channels, whereas no function is observed when the TW site and helix A, or the TW site and helix B are mutated simultaneously. Our data indicate that the TW site is dispensable for function, contributes to the stabilization of the CaM-Kv7.2 complex and becomes essential when docking to either helix A or when helix B is perturbed. PMID- 26148515 TI - Deoxycytidine production by a metabolically engineered Escherichia coli strain. AB - BACKGROUND: Rational engineering studies for deoxycytidine production were initiated due to low intracellular levels and tight regulation. To achieve high level production of deoxycytidine, a useful precursor of decitabine, genes related to feed-back inhibition as well as the biosynthetic pathway were engineered. Additionally, we predicted the impact of individual gene expression levels on a complex metabolic network by microarray analysis. Based on these findings, we demonstrated rational metabolic engineering strategies capable of producing deoxycytidine. RESULTS: To prepare the deoxycytidine producing strain, we first deleted 3 degradation enzymes in the salvage pathway (deoA, udp, and deoD) and 4 enzymes involved in the branching pathway (dcd, cdd, codA and thyA) to completely eliminate degradation of deoxycytidine. Second, purR, pepA and argR were knocked out to prevent feedback inhibition of CarAB. Third, to enhance influx to deoxycytidine, we investigated combinatorial expression of pyrG, T4 nrdCAB and yfbR. The best strain carried pETGY (pyrG-yfbR) from the possible combinatorial plasmids. The resulting strain showed high deoxycytidine yield (650 mg/L) but co-produced byproducts. To further improve deoxycytidine yield and reduce byproduct formation, pgi was disrupted to generate a sufficient supply of NADPH and ribose. Overall, in shake-flask cultures, the resulting strain produced 967 mg/L of dCyd with decreased byproducts. CONCLUSIONS: We demonstrated that deoxycytidine could be readily achieved by recombineering with biosynthetic genes and regulatory genes, which appeared to enhance the supply of precursors for synthesis of carbamoyl phosphate, based on transcriptome analysis. In addition, we showed that carbon flux rerouting, by disrupting pgi, efficiently improved deoxycytidine yield and decreased byproduct content. PMID- 26148516 TI - Folic acid functionalized ZnO quantum dots for targeted cancer cell imaging. AB - Aqueous stable luminescent ZnO quantum dots (QDs) were successfully synthesized with primary amine groups on the surface, which were designed to conjugate with folic acid (FA) to produce the final ZnO-FA QDs. Such ZnO-FA QDs were able to target some specific cancer cells with overexpressed FA receptors on the membranes and thus differentiate the MCF-7 cancer cells from the normal 293T cells. The nanoparticle uptaking experiments by different cells were carried out in parallel and tracked by confocal laser microscopy dynamically. The results confirmed the specificity of our ZnO-FA QDs towards the FA-receptor overexpressed cancer cells, which had potential for diagnosing cancers in vitro. PMID- 26148517 TI - Wound Healing Following Open Groin Hernia Surgery: The Impact of Comorbidity. AB - BACKGROUND: The aim of this study was to explore the impact of chronic concomitant disease on the risk for postoperative complications following open groin hernia surgery. METHODS: During the study period (2002-2011), 133,074 open repairs were registered in the Swedish Hernia Register. History of peripheral vascular disorders, connective tissue disease, chronic renal failure, obesity, and liver cirrhosis as well as data on hemorrhage or hematoma, wound dehiscence, postoperative infection, and reoperation for superficial infection or bleeding within 30 days after surgery were obtained by matching with the Swedish Patient Register. RESULTS: In the multivariate logistic regression analysis, a significantly increased risk for hemorrhage or hematoma within 30 days after surgery was seen for older patients, males, liver cirrhosis, peripheral vascular disease, and connective tissue disease (p < 0.05). High age (>80 years), previous history of peripheral vascular disease, connective tissue disease, and male gender were risk factors for wound dehiscence (p < 0.05). Liver cirrhosis, chronic kidney disease, BMI > 25, and male gender were associated with increased risk for postoperative wound infection (p < 0.05). A significantly increased risk for reoperation for superficial infection or bleeding was seen in patients with peripheral vascular disease and elderly patients (p < 0.05). CONCLUSION: Risk for postoperative complications in open groin hernia surgery is increased in elderly patients, patients with liver cirrhosis, and those with peripheral vascular disease. The indications for surgery should be weighed against the risk for wound healing complications in these patient groups. Watchful waiting may be an alternative, although this carries the risk of emergency surgery. PMID- 26148518 TI - Diagnosis and Management of Bile Leaks After Hepatectomy: Results of a Prospective Analysis of 475 Hepatectomies. AB - BACKGROUND: The diagnosis and management of bile leaks after hepatectomy are heterogeneous because there is no agreement on the definition of post-hepatectomy biliary fistula. The aim of this study was to validate our definition and management of biliary fistulas after hepatic resection and to compare our results with those proposed by other authors. METHODS: A prospective series of patients who underwent hepatic resection from 2004 to 2012 were established. Drains were maintained for 7 days, and bilirubin was measured on postoperative days (PODs) 3, 5, and 7. Drains were removed if the bilirubin on POD 7 was less than that on POD 5 and less than 171 umol/l (10 mg/dl). A statistical analysis of prognostic factors for biliary fistula was performed. RESULTS: Among 475 consecutive patients, 39 (8%) had biliary fistulas. Only 8 (1.7%) patients required postoperative interventions. In comparison with other studies, we observed a higher rate of bile leaks, but at the same time, we observed a lower rate of interventional procedures. The area under the receiver operating characteristic curve on POD 7 had the highest predictive value (0.81; P < 0.001). Pringle maneuvers lasting >=90 min (OR = 3.4; P < 0.001), extended resections (OR = 6.4; P = 0.007), blood transfusions (OR = 2.4; P = 0.035), and resections including segment I (OR = 1.9; P = 0.033) or segment V (OR = 1.8; P = 0.024) were independently associated with an increased risk of bile leak. CONCLUSIONS: The proposed definition of biliary fistula provides effective recognition of those that are clinically relevant with a reduction of the risk of unrecognized collections and minimal postoperative morbidity. REGISTRATION NUMBER: NCT02056028 ( http://www.clinicaltrials.gov ). PMID- 26148519 TI - Staging Laparoscopy for Patients with cM0, Type 4, and Large Type 3 Gastric Cancer. AB - BACKGROUND: Staging laparoscopy (SL) is considered useful for detecting peritoneal metastasis, a task that is difficult using conventional imaging modalities. However, indications for the procedure remain unclear, with differences evident across reports. The present study aimed to clarify the effectiveness and limitations of SL for patients with type 4 and large type 3 gastric cancer. METHODS: We included 88 patients with cM0, type 4 or large type 3 gastric cancer who underwent SL at the Shizuoka Cancer Center from August 2008 to June 2014, to determine the detection rate of peritoneal metastasis by SL. In addition, we calculated the false-negative rate of SL by recruiting patients who were diagnosed as P0 at SL and underwent laparotomy within 28 days after the SL. RESULTS: P0CY0, P0CY1, P1CY0, and P1CY1 were diagnosed in 41 (46.6 %), 15 (17.0 %), 15 (17.0 %), and 17 (19.3 %) patients, respectively. Accordingly, clinically non-evident peritoneal metastasis was found in 36.3 % of patients, and 53.4 % of patients were diagnosed with stage IV. In addition, 29 patients diagnosed as P0 at SL underwent laparotomy within 28 days after the SL. Among them, peritoneal metastasis was found in five patients. Thus, the false-negative rate was 17.2 % (5/29, 95 % CI 7.6-34.6 %). CONCLUSIONS: SL is useful for detecting previously unsuspected peritoneal metastasis and for avoiding unnecessary laparotomy, although the high false-negative rate cannot be ignored. Patients with cM0, type 4, and large type 3 gastric cancer are considered suitable candidates for SL. PMID- 26148520 TI - Topical Steroids Are Effective in the Treatment of Idiopathic Granulomatous Mastitis. AB - BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare, benign, and chronic disease of the breast. Despite the various treatment approaches described for this disease, a gold standard treatment modality has not yet been defined. In this study, the effect of topical steroids was reviewed and assessed in patients with IGM. METHODS: The records of patients with IGM who were treated only with topical steroids were retrospectively reviewed. Patients were grouped as "completely healed," "inadequately healed," "stable," "worsened," or "recurred" if they had once healed but their symptoms returned. Patients whose skin changes were completely ameliorated were considered "completely healed." RESULTS: All of the patients were women, and the average patient age was 35.7 years (range 24-48 years). During the average follow-up of 37.2 months (range 12-72 months) in patients who received only topical steroid treatment, recurrence was observed in three patients (3/28, 10.7 %), and no side effects or steroid-related complications occurred. CONCLUSIONS: Topical steroids seem to be effective in the treatment of IGM characterized by skin changes. Prospective clinical studies would be useful in determining the clinical efficacy of topical steroids in the treatment of IGM. PMID- 26148521 TI - Liver Resection for Advanced Intrahepatic Cholangiocarcinoma: A Cost-Utility Analysis. AB - BACKGROUND: Data on cost-effectiveness and efficacy of hepatic resection (HR) for advanced intrahepatic cholangiocarcinoma (ICC) are lacking. We sought to estimate the cost-effectiveness of upfront HR resulting in an R1 resection (strategy A) relative to initial systemic chemotherapy (sCT) followed by possible curative HR (strategy B) for patients with advanced ICC. METHODS: A Markov model was developed using data from a systematic literature review. Three base cases were considered: (1) ICC >6 cm (2) ICC with vascular invasion (3) multi-focal ICC. A Monte Carlo simulation assessed outcomes including quality-adjusted life months (QALMs) and incremental cost-effectiveness ratio (ICER). RESULTS: The net health benefit (NHB) of strategy A versus strategy B was 1.4 QALMs for ICC >6 cm and 1.3 QALMs for ICC and vascular invasion; in contrast, there was a negative NHB for HR versus sCT for multi-focal ICC (-0.3 QALMs). In single nodule ICC >6 cm, the ICER of HR versus sCT was $22,482/quality-adjusted life years (QALY) and the ICER of HR versus sCT was $20,953/QALY for ICC with vascular invasion. In multi-focal ICC, the ICER of HR compared with sCT was $83,604/QALY. Patients with a higher American Society of Anesthesiologists score (coefficient 0.94), male sex (coefficient 0.43), low quality of life after sCT (coefficient -2.57) and T3 tumors (coefficient 0.53) had a better NHB for HR relative to sCT followed by potential surgery. CONCLUSIONS: For patients with large ICC or ICC and vascular invasion, HR was more cost-effective than sCT. In contrast, HR was not associated with a positive NHB relative to sCT for patients with multi-focal ICC, and therefore these patients should be treated with sCT rather than HR. PMID- 26148522 TI - Hepatectomy Offers Superior Survival Compared with Non-surgical Treatment for <= 3 Metastatic Tumors with Diameters < 3 cm from Gastric Cancer: A Retrospective Study. AB - BACKGROUND: A consensus has almost been reached in favor of hepatic resection for colorectal cancer metastases. It remains unclear whether resection of gastric cancer metastases in the liver is justified. The purpose of this study was to assess the survival benefit of surgical resection for gastric cancer metastases confined to the liver. METHODS: We reviewed the clinicopathological features and outcome of 107 patients with liver metastases without other non-curative factors from the case records of 5437 gastric cancer patients. These subjects included 34 synchronous cases with tumors present at the time of gastrectomy and 73 metachronous cases with new lesions that appeared after radical gastrectomy. RESULTS: Hepatectomies were performed in nine synchronous and four metachronous cases that had <=3 tumors with diameters <3 cm. The overall survival rates after hepatectomy were significantly higher than those in eligible candidates who did not receive hepatectomy despite having comparable metastatic status (synchronous, n = 8, p = 0.009; metachronous, n = 24, p = 0.016). The survival rate of patients who underwent hepatectomy for synchronous metastases was not inferior to that of patients who underwent hepatectomy for metachronous metastases. The median disease-free interval in metachronous cases was significantly shorter in patients who did not undergo resection than those who underwent resection. However, multivariate analyses revealed that hepatectomy was the only significant (p = 0.001) prognostic factor whereas DFI was not. CONCLUSIONS: Hepatectomy for <=3 metastatic tumors with diameters <3 cm offered superior survival compared with non-surgical treatment even for metastases detected synchronously or within a short period after radical gastrectomy. PMID- 26148523 TI - What's in a Name?: Providing Clarity in the Definition of Minimally Invasive Parathyroidectomy. PMID- 26148524 TI - Timeframe Dependent Fragment Ions Observed in In-Source Decay Experiments with beta-Casein Using MALDI MS. AB - The fragment ions observed with time-of-flight (TOF) and quadrupole ion trap (QIT) TOF mass spectrometers (MS) combined with matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) experiments of phosphorylated analytes beta-casein and its model peptide were compared from the standpoint of the residence timeframe of analyte and fragment ions in the MALDI ion source and QIT cell. The QIT-TOF MS gave fragment c-, z'-, z-ANL, y-, and b-ions, and further degraded fragments originating from the loss of neutrals such as H(2)O, NH(3), CH(2)O (from serine), C2H4O (from threonine), and H(3)PO(4), whereas the TOF MS merely showed MALDI source-generated fragment c-, z'-, z-ANL, y-, and w ions. The fragment ions observed in the QIT-TOF MS could be explained by the injection of the source-generated ions into the QIT cell or a cooperative effect of a little internal energy deposition, a long residence timeframe (140 ms) in the QIT cell, and specific amino acid effects on low-energy CID, whereas the source-generated fragments (c-, z'-, z-ANL, y-, and w-ions) could be a result of prompt radical-initiated fragmentation of hydrogen-abundant radical ions [M + H + H](+) and [M + H - H](-) within the 53 ns timeframe, which corresponds to the delayed extraction time. The further degraded fragment b/y-ions produced in the QIT cell were confirmed by positive- and negative-ion low-energy CID experiments performed on the source-generated ions (c-, z'-, and y-ions). The loss of phosphoric acid (98 u) from analyte and fragment ions can be explained by a slow ergodic fragmentation independent of positive and negative charges. PMID- 26148525 TI - Base-Pairing Energies of Proton-Bound Dimers and Proton Affinities of 1-Methyl-5 Halocytosines: Implications for the Effects of Halogenation on the Stability of the DNA i-Motif. AB - (CCG)(n)*(CGG)(n) trinucleotide repeats have been found to be associated with fragile X syndrome, the most widespread inherited cause of mental retardation in humans. The (CCG)(n)*(CGG)(n) repeats adopt i-motif conformations that are preferentially stabilized by base-pairing interactions of noncanonical proton bound dimers of cytosine (C(+)*C). Halogenated cytosine residues are one form of DNA damage that may be important in altering the structure and stability of DNA or DNA-protein interactions and, hence, regulate gene expression. Previously, we investigated the effects of 5-halogenation and 1-methylation of cytosine on the base-pairing energies (BPEs) using threshold collision-induced dissociation (TCID) techniques. In the present study, we extend our work to include proton bound homo- and heterodimers of cytosine, 1-methyl-5-fluorocytosine, and 1-methyl 5-bromocytosine. All modifications examined here are found to produce a decrease in the BPEs. However, the BPEs of all of the proton-bound dimers examined significantly exceed those of Watson-Crick G*C, neutral C*C base pairs, and various methylated variants such that DNA i-motif conformations should still be preserved in the presence of these modifications. The proton affinities (PAs) of the halogenated cytosines are also obtained from the experimental data by competitive analysis of the primary dissociation pathways that occur in parallel for the proton-bound heterodimers. 5-Halogenation leads to a decrease in the N3 PA of cytosine, whereas 1-methylation leads to an increase in the N3 PA. Thus, the 1-methyl-5-halocytosines exhibit PAs that are intermediate. PMID- 26148526 TI - Improved Differential Ion Mobility Separations Using Linked Scans of Carrier Gas Composition and Compensation Field. AB - Differential ion mobility spectrometry (DIMS) separates ions based on differences in their mobilities in low and high electric fields. When coupled to mass spectrometric analyses, DIMS has the ability to improve signal-to-background by eliminating isobaric and isomeric compounds for analytes in complex mixtures. DIMS separation power, often measured by resolution and peak capacity, can be improved through increasing the fraction of helium in the nitrogen carrier gas. However, because the mobility of ions is higher in helium, a greater number of ions collide with the DIMS electrodes or housing, yielding losses in signal intensity. To take advantage of the benefits of helium addition on DIMS separations and reduce ion losses, linked scans were developed. In a linked scan the helium content of the carrier gas is reduced as the compensation field is increased. Linked scans were compared with conventional compensation field scans with constant helium content for the protein ubiquitin and a tryptic digest of bovine serum albumin (BSA). Linked scans yield better separation of ubiquitin charge states and enhanced peak capacities for the analysis of BSA compared with compensation field scans with constant helium carrier gas percentages. Linked scans also offer improved signal intensity retention in comparison to compensation field scans with constant helium percentages in the carrier gas. PMID- 26148527 TI - Highly selective and sensitive nanoprobes for cyanide based on gold nanoclusters with red fluorescence emission. AB - We report a novel and environmentally friendly fluorescent probe for detecting the cyanide ion (CN(-)) using L-amino acid oxidase (LAAOx)-protected Au nanoclusters (LAAOx@AuNCs) with red emission. The fluorescence-based sensing behaviour of LAAOx@AuNCs towards anions was investigated in buffered aqueous media. Among the anions studied, CN(-) was found to effectively quench the fluorescence emission of AuNCs based on CN(-) induced Au core decomposition. Excellent sensitivity and selectivity toward the detection of CN(-) in aqueous solution were observed. The CN(-) detection limit was determined to be approximately 180 nM, which is 15 times lower than the maximum level (2700 nM) of CN(-) in drinking water permitted by the World Health Organization (WHO). A linear relationship between the fluorescence intensity and CN(-) concentration was observed in two ranges of CN(-) concentration, including 3.2 * 10(-6) to 3.4 * 10(-5) mol L(-1) and 3.81 * 10(-5) to 1.04 * 10(-4) mol L(-1). The high sensitivity and selectivity to CN(-) among the 17 types of anions make the AuNCs good candidates for use in fluorescent nanoprobes of CN(-). PMID- 26148528 TI - Opinion paper: implementing pig welfare legislation: difficulties and knowledge exchange strategies. PMID- 26148529 TI - Bacterial microcompartments: widespread prokaryotic organelles for isolation and optimization of metabolic pathways. AB - Prokaryotes use subcellular compartments for a variety of purposes. An intriguing example is a family of complex subcellular organelles known as bacterial microcompartments (MCPs). MCPs are widely distributed among bacteria and impact processes ranging from global carbon fixation to enteric pathogenesis. Overall, MCPs consist of metabolic enzymes encased within a protein shell, and their function is to optimize biochemical pathways by confining toxic or volatile metabolic intermediates. MCPs are fundamentally different from other organelles in having a complex protein shell rather than a lipid-based membrane as an outer barrier. This unusual feature raises basic questions about organelle assembly, protein targeting and metabolite transport. In this review, we discuss the three best-studied MCPs highlighting atomic-level models for shell assembly, targeting sequences that direct enzyme encapsulation, multivalent proteins that organize the lumen enzymes, the principles of metabolite movement across the shell, internal cofactor recycling, a potential system of allosteric regulation of metabolite transport and the mechanism and rationale behind the functional diversification of the proteins that form the shell. We also touch on some potential biotechnology applications of an unusual compartment designed by nature to optimize metabolic processes within a cellular context. PMID- 26148531 TI - Role of the Mitochondrial Calcium Uniporter in Rat Hippocampal Neuronal Death After Pilocarpine-Induced Status Epilepticus. AB - The mitochondrial calcium uniporter (MCU) is reportedly involved in oxidative stress, apoptosis, and many neurological diseases. However, the role of the MCU in epilepsy remains unknown. In this study, we found that the MCU inhibitor Ru360 significantly attenuated neuronal death and exerted an anti-apoptotic effect on rat hippocampal neurons after pilocarpine-induced status epilepticus (SE), while the MCU activator spermine increased seizure-induced neuronal death and apoptosis. In addition, Ru360 decreased the level of seizure-induced reactive oxygen species (ROS) in mitochondria isolated from rat hippocampi. Moreover, Ru360 restored the altered mitochondrial membrane potential and cytochrome c (CytC) release in epileptic hippocampi. However, spermine treatment exerted an opposite effect on seizure-induced ROS production and mitochondrial membrane potential alteration and CytC release compared with Ru360 treatment. Altogether, the findings of this study suggest that MCU inhibition exerts a neuroprotective effect on seizure-induced brain injury possibly through the mitochondria/ROS/CytC pathway. PMID- 26148530 TI - Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns. AB - Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed. PMID- 26148534 TI - ? PMID- 26148533 TI - Non-straight cell edges are important to invasion and engulfment as demonstrated by cell mechanics model. AB - Computational models of cell-cell mechanical interactions typically simulate sorting and certain other motions well, but as demands on these models continue to grow, discrepancies between the cell shapes, contact angles and behaviours they predict and those that occur in real cells have come under increased scrutiny. To investigate whether these discrepancies are a direct result of the straight cell-cell edges generally assumed in these models, we developed a finite element model that approximates cell boundaries using polylines with an arbitrary number of segments. We then compared the predictions of otherwise identical polyline and monoline (straight-edge) models in a variety of scenarios, including annealing, single- and multi-cell engulfment, sorting, and two forms of mixing- invasion and checkerboard pattern formation. Keeping cell-cell edges straight influences cell motion, cell shape, contact angle, and boundary length, especially in cases where one cell type is pulled between or around cells of a different type, as in engulfment or invasion. These differences arise because monoline cells have restricted deformation modes. Polyline cells do not face these restrictions, and with as few as three segments per edge yielded realistic edge shapes and contact angle errors one-tenth of those produced by monoline models, making them considerably more suitable for situations where angles and shapes matter, such as validation of cellular force-inference techniques. The findings suggest that non-straight cell edges are important both in modelling and in nature. PMID- 26148532 TI - Rapid Eye Movement Sleep Deprivation Associated Increase in Na-K ATPase Activity in the Rat Brain is Due to Noradrenaline Induced alpha1-Adrenoceptor Mediated Increased alpha-Subunit of the Enzyme. AB - Rapid eye movement sleep (REMS) modulates Na-K ATPase activity and maintains brain excitability. REMS deprivation (REMSD)-associated increased Na-K ATPase activity is mediated by noradrenaline (NA) acting on alpha1-adrenoceptor (AR) in the brain. It was shown that NA-induced increased Na-K ATPase activity was due to allosteric modulation as well as increased turnover of the enzyme. Although the former has been studied in detail, our understanding on the latter was lacking, which we have studied. Male Wistar rats were REMS deprived for 4-days by classical flower-pot method; suitable control experiments were conducted. In another set, alpha1-AR antagonist prazosin (PRZ) was i.p. injected 48 h REMSD onward. At the end of experiments rats were sacrificed by cervical dislocation and brains were removed. Synaptosomes prepared from the brains were used to estimate Na-K ATPase activity as well as protein expressions of different isoforms of the enzyme subunits using western blot. REMSD significantly increased synaptosomal Na-K ATPase activity and that was due to differential increase in the expressions of alpha1-, alpha2- and alpha3-isoforms, but not that of beta1- and beta2-isoforms. PRZ reduced the REMSD-induced increased Na-K ATPase activity and protein expressions. We also observed that the increased Na-K ATPase subunit expression was not due to enhanced mRNA synthesis, which suggests the possibility of post-transcriptional regulation. Thus, the findings suggest that REMSD associated increased Na-K ATPase activity is due to elevated level of alpha subunit of the enzyme and that is induced by NA acting on alpha1-AR mediated mRNA stabilization. PMID- 26148535 TI - Congenital orbital primitive neuroectodermal tumour. PMID- 26148536 TI - Marginal Bayesian nonparametric model for time to disease arrival of threatened amphibian populations. AB - The global emergence of Batrachochytrium dendrobatidis (Bd) has caused the extinction of hundreds of amphibian species worldwide. It has become increasingly important to be able to precisely predict time to Bd arrival in a population. The data analyzed herein present a unique challenge in terms of modeling because there is a strong spatial component to Bd arrival time and the traditional proportional hazards assumption is grossly violated. To address these concerns, we develop a novel marginal Bayesian nonparametric survival model for spatially correlated right-censored data. This class of models assumes that the logarithm of survival times marginally follow a mixture of normal densities with a linear dependent Dirichlet process prior as the random mixing measure, and their joint distribution is induced by a Gaussian copula model with a spatial correlation structure. To invert high-dimensional spatial correlation matrices, we adopt a full-scale approximation that can capture both large- and small-scale spatial dependence. An efficient Markov chain Monte Carlo algorithm with delayed rejection is proposed for posterior computation, and an R package spBayesSurv is provided to fit the model. This approach is first evaluated through simulations, then applied to threatened frog populations in Sequoia-Kings Canyon National Park. PMID- 26148537 TI - Antifungal prescribing pattern and attitude towards the treatment of oral candidiasis among dentists in Jordan. AB - AIM: The aim of this study was to evaluate the attitude of Jordanian dentists towards the treatment of oral candidiasis and their current antifungal prescribing habits, shedding more light on the possible influence of their socio professional factors on the pattern of prescribing and practice. METHODS: A structured validated questionnaire was developed and tested; it was then emailed to a random sample of 600 Jordanian dental practitioners during the period of this cross-sectional survey. The questionnaire recorded practitioners' personal details and their attitude and prescribing of antifungal therapy for oral candidiasis. Statistical significance was based on probability values of <0.05 and was measured using the chi-square and Fisher's exact tests. Multiple logistic regression analysis was used to analyse the influence of respondents' socio professional factors on their attitude towards oral candidiasis. RESULTS: Of the 423 questionnaires returned, only 330 were included. The attitude of respondents was significantly influenced by their experience [odds ratio (OR) = 0.14; P < 0.001] and workplace (OR = 4.70; P < 0.001). Nystatin was the most commonly prescribed antifungal agent (78.2%), followed by miconazole (62.4%), which was prescribed for topical use. Systemic antifungals were prescribed by 21.2% of respondents, with a significant (P < 0.05) association with the country in which their qualification was obtained. CONCLUSION: The attitude towards the treatment of oral candidiasis is much better among the least-experienced dentists working in private practice. Nystatin and miconazole are the most popular choices of antifungal agents among Jordanian dentists. PMID- 26148538 TI - Hui and Walter's latent-class model extended to estimate diagnostic test properties from surveillance data: a latent model for latent data. AB - Diagnostic test sensitivity and specificity are probabilistic estimates with far reaching implications for disease control, management and genetic studies. In the absence of 'gold standard' tests, traditional Bayesian latent class models may be used to assess diagnostic test accuracies through the comparison of two or more tests performed on the same groups of individuals. The aim of this study was to extend such models to estimate diagnostic test parameters and true cohort specific prevalence, using disease surveillance data. The traditional Hui-Walter latent class methodology was extended to allow for features seen in such data, including (i) unrecorded data (i.e. data for a second test available only on a subset of the sampled population) and (ii) cohort-specific sensitivities and specificities. The model was applied with and without the modelling of conditional dependence between tests. The utility of the extended model was demonstrated through application to bovine tuberculosis surveillance data from Northern and the Republic of Ireland. Simulation coupled with re-sampling techniques, demonstrated that the extended model has good predictive power to estimate the diagnostic parameters and true herd-level prevalence from surveillance data. Our methodology can aid in the interpretation of disease surveillance data, and the results can potentially refine disease control strategies. PMID- 26148539 TI - What Is the Best Criterion for Repetition of Fine-Needle Aspiration in Thyroid Nodules with Initially Benign Cytology? AB - BACKGROUND: Traditionally, repetition of fine-needle aspiration (FNA) is indicated for thyroid nodules with initially benign cytology if they exhibit growth. The importance of a repetition has also been demonstrated in the case of suspicious ultrasonography (US) findings. Some authors even consider routine repetition of FNA. The objective of this study was to evaluate the best criterion for FNA repetition in thyroid nodules with initially benign cytology. METHODS: This was a prospective study. Patients with solid nodules that initially showed a benign cytology were selected. The first group was formed by nodules exhibiting suspicious features on initial US (group A, n = 55). The other group consisted of growing nodules without suspicious US features (group B, n = 82). Nongrowing nodules without suspicious features on initial US were divided into two groups: nodules that became suspicious on US (group C.1, n = 18) and those that continued to be unsuspicious (group C.2, n = 398). RESULTS: In group A, the second FNA resulted in the diagnosis of malignancy in 10 cases (18.2%). In group B, malignancy was confirmed in two cases (2.4%). In group C.1, two nodules were confirmed to be malignant (11.1%). No case of carcinoma was observed in group C.2. Considering the sensitivity and number of FNA biopsies necessary for the detection of each false-negative case of the first FNA, the best criterion to repeat FNA was a suspicious initial or subsequent US. The growth of nodules with unsuspicious US findings was of poorly specificity and required a larger number of FNA biopsies to detect one case of malignancy. CONCLUSIONS: Ultrasonographic features of the nodule are the best parameter for the indication of FNA repetition in nodules with initially benign cytology, while the growth of nodules with unsuspicious US findings has a poor positive predictive value for malignancy. PMID- 26148540 TI - Fertility treatments and adverse perinatal outcomes in a population-based sampling of births in Florida, Maryland, and Utah: a cross-sectional study. AB - OBJECTIVE: To investigate perinatal outcomes associated with fertility treatments, including assisted reproductive technology (ART), intrauterine insemination with ovulation stimulation (IUI), and ovulation stimulation alone (OS). DESIGN: Population-representative cross-sectional survey of women with live births, 2004-2008. SETTING: Florida, Maryland, and Utah, USA. SAMPLE: 21 803 women, weighted to represent 1 022 597 women. METHODS: Survey and birth certificate data were analysed with logistic regression models adjusted for age, education, race, income, and parity, using separate models for singletons and all births. We used two referent groups: (1) women who never used fertility treatment and (2) subfertile women conceiving without treatment. MAIN OUTCOME MEASURES: Preterm birth (<37 weeks), very preterm birth (<34 weeks), low birthweight (<2500 g), and very low birthweight (<1500 g). RESULTS: Referent group 1: In singletons, ART was associated with preterm birth (OR 3.28; 95% CI 1.74, 6.20) and low birthweight (OR 2.91; 95% CI 1.99, 4.26). OS was also associated with low birthweight (OR 1.62; 95% CI 1.19, 2.19). Including all births, treatment was associated with preterm birth and low birthweight: ART (OR 6.21; 95% CI 4.21, 9.16 and OR 6.51; 95% CI 4.85, 8.73); IUI (OR 2.10; 95% CI 1.24, 3.56 and OR 2.41; 95% CI 1.54, 3.76); OS (OR 1.40; 95% CI 1.01, 1.94 and OR 2.10; 95% CI 1.60, 2.75), respectively. Referent group 2: ART was associated with both outcomes in all births, but not singletons. CONCLUSIONS: Preterm birth and low birthweight associated with fertility treatments are largely attributable to multiple gestation, but are also related to underlying subfertility. TWEETABLE ABSTRACT: Preterm birth is associated with subfertility, and with fertility treatments through multiple gestation. PMID- 26148541 TI - Correspondence: Some general points regarding Ledberg and Wennberg, BMC Medical Research Methodology 2014 April 27;14:58. AB - The purpose of this note is to contribute some general points on a recent paper by Ledberg and Wennberg (BMC Med Res Meth 14:58, 2014) which need to be rectified. They advocate the capture-removal estimator. First, we will discuss drawbacks of this estimator in comparison to the Lincoln-Petersen estimator. Second, we show that their evaluation of the Chao estimator is flawed. We conclude that some statements in Ledberg and Wennberg with respect to Chao's estimator and removal estimation need to be taken with great caution. PMID- 26148542 TI - Two Types of Discontinuous Percolation Transitions in Cluster Merging Processes. AB - Percolation is a paradigmatic model in disordered systems and has been applied to various natural phenomena. The percolation transition is known as one of the most robust continuous transitions. However, recent extensive studies have revealed that a few models exhibit a discontinuous percolation transition (DPT) in cluster merging processes. Unlike the case of continuous transitions, understanding the nature of discontinuous phase transitions requires a detailed study of the system at hand, which has not been undertaken yet for DPTs. Here we examine the cluster size distribution immediately before an abrupt increase in the order parameter of DPT models and find that DPTs induced by cluster merging kinetics can be classified into two types. Moreover, the type of DPT can be determined by the key characteristic of whether the cluster kinetic rule is homogeneous with respect to the cluster sizes. We also establish the necessary conditions for each type of DPT, which can be used effectively when the discontinuity of the order parameter is ambiguous, as in the explosive percolation model. PMID- 26148543 TI - Synthesis of Ir(III) complexes with Tp(Me2) and acac ligands and their reactivity with electrophiles. AB - The reaction of the bis(ethylene) complex [Tp(Me2)Ir(C2H4)2] () (Tp(Me2) = hydrotris(3,5-dimethylpyrazolyl)borate) with an excess of 2,4-pentanedione (acetylacetone, Hacac) at 70 degrees C produced a mixture of the Ir(iii) complex [Tp(Me2)Ir(acac)(C2H5)] () as a major product (67% yield) and two other side complexes [Tp(Me2)Ir(acac)(H)] () and [Tp(Me2)Ir(C9H14O2)] () in 20 and 13% yields, respectively. According to the proposed reaction mechanism and DFT calculations, complexes and are generated from an 18e(-) intermediate [Tp(Me2)Ir(C2H4)(acac)(C2H3)] () which undergoes either hydrogen insertion or beta-hydride elimination followed by the subsequent loss of a molecule of ethylene. The lowest yielding complex which features a 2-iridafuran is presumably generated from an unusual thermal coupling between one vinylic and one acac moiety. The availability of the acidic alpha-proton of the acac ligand was tested by the treatment of complex with Br2 and Cu(NO3)2 rendering the substitution complexes [Tp(3-Br,Me2)Ir(3-Br-acac)Br] () and [Tp(Me2)Ir(3-NO2-acac)(C2H5)] () in good yields. The series of heteroleptic iridium(iii) compounds display air and moisture stability and have been characterized by NMR, IR, and elemental analyses, and, in the case of , and , by single-crystal X-ray diffraction analyses. PMID- 26148544 TI - Mucosal Alpha-Papillomavirus (HPV89) in a rare skin lesion. AB - BACKGROUND: Apocrine acrosyringeal keratosis is a rare skin lesion showing a unique benign keratotic lesion associated with syringocystoadenoma papilliferum. It is characterized by an exophytic proliferation of the epidermis with two distinct keratinocytic structures: a) columns of hyperkeratotic mass surrounded by acanthotic epidermis and b) papillated and/or cystic invaginations typical of syringocystoadenoma papilliferum. No causative agents were reported. FINDINGS: The present report describes a typical case of apocrine acrosyringeal keratosis localized in the right retro-auricular area of 57-year-old man in which the presence of HPV was evaluated. PCR analysis and direct sequencing revealed the presence of HPV 89. The presence of this low risk mucosal HPV in a skin localization was never reported as well as in association with this rare tumor. Furthermore rolling circle amplification, RT-PCR and in situ hybridization confirmed the presence of a transcriptionally active HPV 89. CONCLUSIONS: Taken together our results suggest that HPV89 plays a role in apocrine acrosyringeal keratosis with syringocystoadenoma papilliferum, in consideration of the documented biological activity of the virus. The association of low risk mucosal HPV infection with this skin lesion opens new perspectives in its clinical management. Further studies on samples from other patients are needed to confirm this association. PMID- 26148545 TI - UK women's experiences of breastfeeding and additional breastfeeding support: a qualitative study of Baby Cafe services. AB - BACKGROUND: Whilst 81 % of UK women initiate breastfeeding, there is a steep decline in breastfeeding rates during the early postnatal period, with just 55 % of women breastfeeding at six weeks. 80 % of these women stopped breastfeeding sooner than they intended, with women citing feeding difficulties and lack of adequate support. As part of efforts to increase breastfeeding continuation rates, many public and voluntary organisations offer additional breastfeeding support services, which provide practical support in the early postnatal period and beyond. This paper focuses on the qualitative experiences of UK users of Baby Cafe services to examine their experiences of breastfeeding and breastfeeding support. METHODS: The study was based upon in-depth interviews and focus groups with users of eight Baby Cafe breastfeeding support groups across the UK. Thirty six interviews and five focus groups were conducted with a total of fifty-one mothers using the service. Interviews and group discussions were analysed using N Vivo software to draw out key themes and discussions. RESULTS: Whilst each mother's infant feeding journey is unique, reflecting her own personal circumstances and experiences, several themes emerged strongly from the data. Many women felt that they had been given unrealistic expectations of breastfeeding by professionals keen to promote the benefits. This left them feeling unprepared when they encountered pain, problems and relentlessness of early infant feeding, leading to feelings of guilt and inadequacy over their feeding decisions. Mothers valued the combination of expert professional and peer support provided by Baby Cafe services and emphasised the importance of social support from other mothers in enabling them to continue feeding for as long as they wished. CONCLUSIONS: The research emphasises the need for realistic rather than idealistic antenatal preparation and the importance of timely and parent centred breastfeeding support, particularly in the immediate postnatal weeks. The findings suggest that effective social support, combined with reassurance and guidance from skilled practitioners, can help women to overcome difficulties and find confidence in their own abilities to achieve their feeding goals. However, further work is needed to make sure such services are readily accessible to women from all sectors of the community. PMID- 26148546 TI - Reliability and validity of the Chinese version of the Short Musculoskeletal Function Assessment questionnaire in patients with skeletal muscle injury of the upper or lower extremities. AB - BACKGROUND: The Short Musculoskeletal Function Assessment (SMFA) questionnaire is one of the most commonly used scales to evaluate functional status and quality of life (QOL) of patients with a broad range of musculoskeletal disorders. However, a Chinese version of the SMFA questionnaire for the psychometric properties of skeletal muscle injury patients in China is still lacking. The current study translated the SMFA into Chinese and assessed its reliability and validity among Chinese patients with skeletal muscle injury of the upper or lower extremities. METHODS: The original SMFA was translated from English into Chinese and culturally adapted according to cross-cultural adaptation guidelines. A multicenter cross-sectional study was conducted, comprising 339 skeletal muscle injury patients (aged 20-75 years) from 4 hospitals. The SMFA, the health survey short form (SF-36) along with a region-specific questionnaire (including the disabilities of the arm, shoulder, and hand questionnaire (DASH), the hip disability and osteoarthritis outcome score (HOOS), the knee injury and osteoarthritis outcome score (KOOS), and the foot function index (FFI)) were completed according to the region of injury. Reliability was estimated from the internal consistency using Cronbach's alpha and validity was assessed via convergent validity, known-groups comparison, and construct validity. RESULTS: Cronbach's alpha coefficient was over 0.75 for two subscales and four categories of the SMFA, suggesting that the internal consistency reliability of the SMFA was satisfactory. Known-groups comparison showed that the dysfunction index and the bother index of the SMFA discriminated well between patients who differed in age, gender, injury location, and operation status rather than in subgroups based on the body mass index (BMI). The convergent validity of the SMFA was good, as moderate to excellent correlations were found between the subscales of the SMFA and the four subscales of SF-36 (physical function, role-physical, bodily pain, and social functioning) and the region-specific questionnaires. The construct validity was proved by the presence of a six-factor structure that accounted for 66.85 % of the variance. CONCLUSION: The Chinese version of the SMFA questionnaire is a reliable and valid instrument to measure patient-reported impact of musculoskeletal injuries in the upper or lower extremities. PMID- 26148547 TI - A novel homozygous variant in the dsp gene underlies the first case of non syndromic form of alopecia. AB - Autosomal recessive forms of hair loss (alopecia) disorders have previously been associated with variants in at least five different genes including hairless (HR), desmoglein-4 (DSG4), desmocollin-3 (DSC3), lipase-H (LIPH), and lysophosphatidic acid receptor 6 (LPAR6). Here, we report the first familial case of alopecia resulting from a novel homozygous variant in the DSP gene. Since previous reports indicated the presence of heart abnormalities in patients carrying variants in the DSP gene; therefore, the echocardiographic evaluations of all affected members were performed. The results clearly excluded the presence of any form of heart abnormality in patients of the present family. Human genome scan mapped a disease locus on chromosome 6p25.1-p23, harboring DSP gene. Sequence analysis identified a novel homozygous missense variant [c.1493C > T (p.Pro498Leu)] in the DSP gene as the underlying genetic cause of non-syndromic alopecia in the family. The transition alters the completely conserved Pro498 residue in the SH3 domain of plakin that contributes to the stability and rigidity of this subfamily of spectrin repeats (SRs) containing proteins. Our study strengthens the evidence that hereditary hair loss disorders are genetically heterogeneous and imply that isolated form of alopecia is allelic with cardiocutaneous syndromes. PMID- 26148548 TI - Using Multi-Scale Measurements to Improve Methane Emission Estimates from Oil and Gas Operations in the Barnett Shale Region, Texas. PMID- 26148549 TI - Aircraft-Based Measurements of Point Source Methane Emissions in the Barnett Shale Basin. AB - We report measurements of methane (CH4) emission rates observed at eight different high-emitting point sources in the Barnett Shale, Texas, using aircraft based methods performed as part of the Barnett Coordinated Campaign. We quantified CH4 emission rates from four gas processing plants, one compressor station, and three landfills during five flights conducted in October 2013. Results are compared to other aircraft- and surface-based measurements of the same facilities, and to estimates based on a national study of gathering and processing facilities emissions and 2013 annual average emissions reported to the U.S. EPA Greenhouse Gas Reporting Program (GHGRP). For the eight sources, CH4 emission measurements from the aircraft-based mass balance approach were a factor of 3.2-5.8 greater than the GHGRP-based estimates. Summed emissions totaled 7022 +/- 2000 kg hr(-1), roughly 9% of the entire basin-wide CH4 emissions estimated from regional mass balance flights during the campaign. Emission measurements from five natural gas management facilities were 1.2-4.6 times larger than emissions based on the national study. Results from this study were used to represent "super-emitters" in a newly formulated Barnett Shale Inventory, demonstrating the importance of targeted sampling of "super-emitters" that may be missed by random sampling of a subset of the total. PMID- 26148551 TI - Methane Emissions from Leak and Loss Audits of Natural Gas Compressor Stations and Storage Facilities. AB - As part of the Environmental Defense Fund's Barnett Coordinated Campaign, researchers completed leak and loss audits for methane emissions at three natural gas compressor stations and two natural gas storage facilities. Researchers employed microdilution high-volume sampling systems in conjunction with in situ methane analyzers, bag samples, and Fourier transform infrared analyzers for emissions rate quantification. All sites had a combined total methane emissions rate of 94.2 kg/h, yet only 12% of the emissions total resulted from leaks. Methane slip from exhausts represented 44% of the total emissions. Remaining methane emissions were attributed to losses from pneumatic actuators and controls, engine crankcases, compressor packing vents, wet seal vents, and slop tanks. Measured values were compared with those reported in literature. Exhaust methane emissions were lower than emissions factor estimates for engine exhausts, but when combined with crankcase emissions, measured values were 11.4% lower than predicted by AP-42 as applicable to emissions factors for four-stroke, lean-burn engines. Average measured wet seal emissions were 3.5 times higher than GRI values but 14 times lower than those reported by Allen et al. Reciprocating compressor packing vent emissions were 39 times higher than values reported by GRI, but about half of values reported by Allen et al. Though the data set was small, researchers have suggested a method to estimate site-wide emissions factors for those powered by four-stroke, lean-burn engines based on fuel consumption and site throughput. PMID- 26148550 TI - Aircraft-Based Estimate of Total Methane Emissions from the Barnett Shale Region. AB - We present estimates of regional methane (CH4) emissions from oil and natural gas operations in the Barnett Shale, Texas, using airborne atmospheric measurements. Using a mass balance approach on eight different flight days in March and October 2013, the total CH4 emissions for the region are estimated to be 76 +/- 13 * 10(3) kg hr(-1) (equivalent to 0.66 +/- 0.11 Tg CH4 yr(-1); 95% confidence interval (CI)). We estimate that 60 +/- 11 * 10(3) kg CH4 hr(-1) (95% CI) are emitted by natural gas and oil operations, including production, processing, and distribution in the urban areas of Dallas and Fort Worth. This estimate agrees with the U.S. Environmental Protection Agency (EPA) estimate for nationwide CH4 emissions from the natural gas sector when scaled by natural gas production, but it is higher than emissions reported by the EDGAR inventory or by industry to EPA's Greenhouse Gas Reporting Program. This study is the first to show consistency between mass balance results on so many different days and in two different seasons, enabling better quantification of the related uncertainty. The Barnett is one of the largest production basins in the United States, with 8% of total U.S. natural gas production, and thus, our results represent a crucial step toward determining the greenhouse gas footprint of U.S. onshore natural gas production. PMID- 26148552 TI - Characterizing Fugitive Methane Emissions in the Barnett Shale Area Using a Mobile Laboratory. AB - Atmospheric methane (CH4) was measured using a mobile laboratory to quantify fugitive CH4 emissions from Oil and Natural Gas (ONG) operations in the Barnett Shale area. During this Barnett Coordinated Campaign we sampled more than 152 facilities, including well pads, compressor stations, gas processing plants, and landfills. Emission rates from several ONG facilities and landfills were estimated using an Inverse Gaussian Dispersion Model and the Environmental Protection Agency (EPA) Model AERMOD. Model results show that well pads emissions rates had a fat-tailed distribution, with the emissions linearly correlated with gas production. Using this correlation, we estimated a total well pad emission rate of 1.5 * 10(5) kg/h in the Barnett Shale area. It was found that CH4 emissions from compressor stations and gas processing plants were substantially higher, with some "super emitters" having emission rates up to 3447 kg/h, more then 36,000-fold higher than reported by the Environmental Protection Agency (EPA) Greenhouse Gas Reporting Program (GHGRP). Landfills are also a significant source of CH4 in the Barnett Shale area, and they should be accounted for in the regional budget of CH4. PMID- 26148553 TI - Constructing a Spatially Resolved Methane Emission Inventory for the Barnett Shale Region. AB - Methane emissions from the oil and gas industry (O&G) and other sources in the Barnett Shale region were estimated by constructing a spatially resolved emission inventory. Eighteen source categories were estimated using multiple data sets, including new empirical measurements at regional O&G sites and a national study of gathering and processing facilities. Spatially referenced activity data were compiled from federal and state databases and combined with O&G facility emission factors calculated using Monte Carlo simulations that account for high emission sites representing the very upper portion, or fat-tail, in the observed emissions distributions. Total methane emissions in the 25-county Barnett Shale region in October 2013 were estimated to be 72,300 (63,400-82,400) kg CH4 h(-1). O&G emissions were estimated to be 46,200 (40,000-54,100) kg CH4 h(-1) with 19% of emissions from fat-tail sites representing less than 2% of sites. Our estimate of O&G emissions in the Barnett Shale region was higher than alternative inventories based on the United States Environmental Protection Agency (EPA) Greenhouse Gas Inventory, EPA Greenhouse Gas Reporting Program, and Emissions Database for Global Atmospheric Research by factors of 1.5, 2.7, and 4.3, respectively. Gathering compressor stations, which accounted for 40% of O&G emissions in our inventory, had the largest difference from emission estimates based on EPA data sources. Our inventory's higher O&G emission estimate was due primarily to its more comprehensive activity factors and inclusion of emissions from fat-tail sites. PMID- 26148554 TI - Airborne Ethane Observations in the Barnett Shale: Quantification of Ethane Flux and Attribution of Methane Emissions. AB - We present high time resolution airborne ethane (C2H6) and methane (CH4) measurements made in March and October 2013 as part of the Barnett Coordinated Campaign over the Barnett Shale formation in Texas. Ethane fluxes are quantified using a downwind flight strategy, a first demonstration of this approach for C2H6. Additionally, ethane-to-methane emissions ratios (C2H6:CH4) of point sources were observationally determined from simultaneous airborne C2H6 and CH4 measurements during a survey flight over the source region. Distinct C2H6:CH4 * 100% molar ratios of 0.0%, 1.8%, and 9.6%, indicative of microbial, low-C2H6 fossil, and high-C2H6 fossil sources, respectively, emerged in observations over the emissions source region of the Barnett Shale. Ethane-to-methane correlations were used in conjunction with C2H6 and CH4 fluxes to quantify the fraction of CH4 emissions derived from fossil and microbial sources. On the basis of two analyses, we find 71-85% of the observed methane emissions quantified in the Barnett Shale are derived from fossil sources. The average ethane flux observed from the studied region of the Barnett Shale was 6.6 +/- 0.2 * 10(3) kg hr(-1) and consistent across six days in spring and fall of 2013. PMID- 26148555 TI - Toward a Functional Definition of Methane Super-Emitters: Application to Natural Gas Production Sites. AB - Emissions from natural gas production sites are characterized by skewed distributions, where a small percentage of sites-commonly labeled super-emitters account for a majority of emissions. A better characterization of super-emitters is needed to operationalize ways to identify them and reduce emissions. We designed a conceptual framework that functionally defines superemitting sites as those with the highest proportional loss rates (methane emitted relative to methane produced). Using this concept, we estimated total methane emissions from natural gas production sites in the Barnett Shale; functionally superemitting sites accounted for roughly three-fourths of total emissions. We discuss the potential to reduce emissions from these sites, under the assumption that sites with high proportional loss rates have excess emissions resulting from abnormal or otherwise avoidable operating conditions, such as malfunctioning equipment. Because the population of functionally superemitting sites is not expected to be static over time, continuous monitoring will likely be necessary to identify them and improve their operation. This work suggests that achieving and maintaining uniformly low emissions across the entire population of production sites will require mitigation steps at a large fraction of sites. PMID- 26148556 TI - Integrating Source Apportionment Tracers into a Bottom-up Inventory of Methane Emissions in the Barnett Shale Hydraulic Fracturing Region. AB - A growing dependence on natural gas for energy may exacerbate emissions of the greenhouse gas methane (CH4). Identifying fingerprints of these emissions is critical to our understanding of potential impacts. Here, we compare stable isotopic and alkane ratio tracers of natural gas, agricultural, and urban CH4 sources in the Barnett Shale hydraulic fracturing region near Fort Worth, Texas. Thermogenic and biogenic sources were compositionally distinct, and emissions from oil wells were enriched in alkanes and isotopically depleted relative to natural gas wells. Emissions from natural gas production varied in delta(13)C and alkane ratio composition, with deltaD-CH4 representing the most consistent tracer of natural gas sources. We integrated our data into a bottom-up inventory of CH4 for the region, resulting in an inventory of ethane (C2H6) sources for comparison to top-down estimates of CH4 and C2H6 emissions. Methane emissions in the Barnett are a complex mixture of urban, agricultural, and fossil fuel sources, which makes source apportionment challenging. For example, spatial heterogeneity in gas composition and high C2H6/CH4 ratios in emissions from conventional oil production add uncertainty to top-down models of source apportionment. Future top down studies may benefit from the addition of deltaD-CH4 to distinguish thermogenic and biogenic sources. PMID- 26148558 TI - Graphene wrapped ordered LiNi0.5Mn1.5O4 nanorods as promising cathode material for lithium-ion batteries. AB - LiNi0.5Mn1.5O4 nanorods wrapped with graphene nanosheets have been prepared and investigated as high energy and high power cathode material for lithium-ion batteries. The structural characterization by X-ray diffraction, Raman spectroscopy, and Fourier transform infrared spectroscopy indicates the LiNi0.5Mn1.5O4 nanorods prepared from beta-MnO2 nanowires have ordered spinel structure with P4332 space group. The morphological characterization by scanning electron microscopy and transmission electron microscopy reveals that the LiNi0.5Mn1.5O4 nanorods of 100-200 nm in diameter are well dispersed and wrapped in the graphene nanosheets for the composite. Benefiting from the highly conductive matrix provided by graphene nanosheets and one-dimensional nanostructure of the ordered spinel, the composite electrode exhibits superior rate capability and cycling stability. As a result, the LiNi0.5Mn1.5O4-graphene composite electrode delivers reversible capacities of 127.6 and 80.8 mAh g(-1) at 0.1 and 10 C, respectively, and shows 94% capacity retention after 200 cycles at 1 C, greatly outperforming the bare LiNi0.5Mn1.5O4 nanorod cathode. The outstanding performance of the LiNi0.5Mn1.5O4-graphene composite makes it promising as cathode material for developing high energy and high power lithium ion batteries. PMID- 26148557 TI - Reorganization of metastamiRs in the evolution of metastatic aggressive neuroblastoma cells. AB - BACKGROUND: MetastamiRs have momentous clinical relevance and have been correlated with disease progression in many tumors. In this study, we identified neuroblastoma metastamiRs exploiting unique mouse models of favorable and high risk metastatic human neuroblastoma. Further, we related their deregulation to the modulation of target proteins and established their association with clinical outcomes. RESULTS: Whole genome miRNA microarray analysis identified 74 metastamiRs across the manifold of metastatic tumors. RT-qPCR on select miRNAs validated profile expression. Results from bio-informatics across the ingenuity pathway, miRCancer, and literature data-mining endorsed the expression of these miRNAs in multiple tumor systems and showed their role in metastasis, identifying them as metastamiRs. Immunoblotting and TMA-IHC analyses revealed alterations in the expression/phosphorylation of metastamiRs' targets, including ADAMTS-1, AKT1/2/3, ASK1, AURKbeta, Birc1, Birc2, Bric5, beta-CATENIN, CASP8, CD54, CDK4, CREB, CTGF, CXCR4, CYCLIN-D1, EGFR, ELK1, ESR1, CFOS, FOSB, FRA, GRB10, GSK3beta, IL1alpha, JUND, kRAS, KRTAP1, MCP1, MEGF10, MMP2, MMP3, MMP9, MMP10, MTA2, MYB, cMYC, NF2, NOS3, P21, pP38, PTPN3, CLEAVED PARP, PKC, SDF-1beta, SEMA3D, SELE, STAT3, TLR3, TNFalpha, TNFR1, and VEGF in aggressive cells ex vivo and in a manifold of metastatic tumors in vivo. miRNA mimic (hsa-miR-125b, hsa-miR-27b, hsa-miR-93, hsa-miR-20a) and inhibitor (hsa-miR-1224-3p, hsa-miR-1260) approach for select miRNAs revealed the direct influence of the altered metastamiRs in the regulation of identified protein targets. Clinical outcome association analysis with the validated metastamiRs' targets corresponded strongly with poor overall and relapse-free survival. CONCLUSIONS: For the first time, these results identified a comprehensive list of neuroblastoma metastamiRs, related their deregulation to altered expression of protein targets, and established their association with poor clinical outcomes. The identified set of distinctive neuroblastoma metastamiRs could serve as potential candidates for diagnostic markers for the switch from favorable to high-risk metastatic disease. PMID- 26148559 TI - Rapid weather changes are associated with increased ischemic stroke risk: a case crossover study. AB - Observational studies focusing on absolute meteorological values suggest an association between meteorological parameters and stroke risk but these results are inconsistent and conflicting. Since changes in weather can provoke atrial fibrillation, we examined the association between rapid weather changes and stroke risk in 1694 patients with determinable onset of stroke symptoms in a case crossover study in central Germany. Days one to three before stroke onset were classified as hazard periods and day seven as the respective control period. Risk of ischemic stroke in relation to 24 h differences in mean ambient temperature, relative humidity and atmospheric pressure was determined. The association between temperature and stroke risk appears to be close to linear with an increase in stroke risk of 11 % (odds ratio 1.11, 95 % confidence interval 1.01 1.22) for each 2.9 degrees C temperature decrease over 24 h. In individuals with a higher cardiovascular risk, stroke risk increased by 30 % (1.30, 1.06-1.61). Risk for cardioembolic strokes increased by 26 % (1.26, 1.06-1.50). Rapid positive or negative changes in relative humidity (>5 %) and atmospheric pressure (>10 hPa) increased stroke risk by a maximum of 30 % (1.30, 1.02-1.66) and 63 % (1.63, 1.10-2.42). In individuals with a higher cardiovascular risk, rapid changes in atmospheric pressure were associated with a four-times higher stroke risk (4.56, 1.26-16.43). Our results suggest that rapid decreases in ambient temperature and rapid changes in relative humidity and atmospheric pressure increase stroke risk under temperate climate conditions. Individuals with a high cardiovascular risk profile seem to be at greater risk. PMID- 26148560 TI - Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study. AB - Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors. PMID- 26148562 TI - [Medication-induced dysphagia : A review]. AB - As a highly differentiated physiological process, swallowing may be affected by a variety of confounding factors. Primarily described are swallowing disorders caused by mechanical anatomic changes (e. g., alteration of the cervical spine, goiter), surgery for head and neck tumors, thyroid abnormalities, and neuromuscular disorders. Age-related cerebral neurological and blood vessel associated changes can also cause dysphagia (so-called presbyphagia) or worsen the condition.Medication-associated dysphagia is recognized far less frequently, not paid due attention, or accepted in silence; particularly in older patients. Furthermore, pharmacological interference of different medications is frequently inadequately considered, particularly in the case of polypharmacy.Initial treatment of medication-induced dysphagia includes a critical review of medication status, with the aim of reducing/discontinuing the causative medication by giving precise instructions regarding its administration; as well as antacid medication, diet, and professional oral stimulation or swallowing training.To date, medication-induced dysphagia has not occupied the focus of physicians and therapists. This is despite the fact that many active agents can have a negative effect on swallowing and medication-induced dysphagia caused by polypharmacy is not uncommon, particularly in old age. This article presents an overview of the different classes of drugs in terms of their direct or indirect negative effects on the swallowing function. PMID- 26148561 TI - CD4 + T Cells and Neuroprotection: Relevance to Motoneuron Injury and Disease. AB - We have established a physiologically relevant mechanism of CD4+ T cell-mediated neuroprotection involving axotomized wildtype (WT) mouse facial motoneurons (FMN) with significance in the treatment of amyotrophic lateral sclerosis (ALS), a fatal MN disease. Use of the transgenic mouse model of ALS involving expression of human mutant superoxide dismutase genes (SOD1(G93A); abbreviated here as mSOD1) has accelerated basic ALS research. Superimposition of facial nerve axotomy (FNA) on the mSOD1 mouse during pre-symptomatic stages indicates that they behave like immunodeficient mice in terms of increased FMN loss and decreased functional recovery, through a mechanism that, paradoxically, is not inherent within the MN itself, but, instead, involves a defect in peripheral immune: CNS glial cell interactions. Our goal is to utilize our WT mouse model of immune-mediated neuroprotection after FNA as a template to elucidate how a malfunctioning peripheral immune system contributes to motoneuron cell loss in the mSOD1 mouse. This review will discuss potential immune defects in ALS, as well as provide an up-to-date understanding of how the CD4+ effector T cells provide neuroprotection to motoneurons through regulation of the central microglial and astrocytic response to injury. We will discuss an IL-10 cascade within the facial nucleus that requires a functional CD4+ T cell trigger for activation. The review will discuss the role of T cells in ALS, and our recent reconstitution experiments utilizing our model of T cell-mediated neuroprotection in WT vs mSOD1 mice after FNA. Identification of defects in neural:immune interactions could provide targets for therapeutic intervention in ALS. PMID- 26148563 TI - [Fillers and associated side effects]. AB - BACKGROUND: A variety of fillers is commonly used for tissue augmentation as well as skin rejuvenation, and consist of a large heterogeneous group of biomaterials. The objective was to provide an overview and classification of the most commonly injected filler materials and filler-related complications including therapy. METHOD: A summary of the current literature and common associated side effects is provided from a personal clinical perspective. RESULTS: According to degradability, filler materials can be classified as temporary (degradable), semi permanent, and permanent (nondegradable). Temporary fillers such as hyaluronic acid and collagen are completely degraded by the surrounding tissue within several months. Semi-permanent fillers are degradable, but may induce longer lasting secondary effects. Permanent fillers such as silicone and mineral oil derivatives are not biodegradable and have been increasingly abandoned because of severe and irreversible side effects. The most common filler-related adverse events include pigmentation changes, edema and post-injection deformations. Visible or palpable nodules can be due to filler accumulation, formation of granuloma, or infection. CONCLUSIONS: Substantial knowledge of the chemical and clinical features of the injected materials is indispensable for safe and efficient application. Early recognition of filler-related adverse effects is important to avoid severe complications and to achieve optimal results. PMID- 26148564 TI - [Transfer of autologous fat and plasma : The future of anti-aging medicine?]. AB - BACKGROUND: Aging is a complex process driven by endogenous and exogenous stimuli. The distinct cellular and noncellular components of skin and adjacent connective tissue are constantly and irreversibly degraded during aging. OBJECTIVES: The aim was to provide an overview of the biology of skin aging and the therapeutic options for rejuvenation. METHODS: A review of the current literature and a demonstration of autologous fat transfer and platelet-rich plasma (PRP) are presented from a clinical perspective. RESULTS: The aging process affects cellular components and the extracellular matrix (ECM); thus, the first stage is the degradation of the ECM. The loss of skin elasticity is induced by a breakdown of fibers such as collagen, elastin, or reticulin, whereas the degradation of proteoglycans results in decreased turgor and skin hydration. Synthetic filling agents primarily compensate for volume loss, but do not rejuvenate biologically. In contrast, the transfer of autologous fat and PRP is based on activating stem cell populations and growth factors, in addition to providing volume to target regions. CONCLUSIONS: A profound comprehension of the cellular and molecular mechanisms of aging is important in anti-aging medicine. The transfer of autologous fat and PRP offers interesting alternatives in the sense of more biological skin rejuvenation. PMID- 26148565 TI - Genetic determinants of platelet large-cell ratio, immature platelet fraction, and other platelet-related phenotypes. AB - INTRODUCTION: Platelets play a significant role in arterial thrombosis and are involved also in venous thrombosis. The genetic determinants of several platelet related phenotypes have been studied previously. However, to the best of our knowledge, the genetic determinants of other platelet phenotypes have not been reported such as platelet-large-cell ratio (P-LCR) index, immature platelet fraction (IPF) parameters and overall platelet function measured through the PFA 100 system. MATERIALS AND METHODS: As part of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project, 935 individuals from 35 large Spanish families, ascertained through a proband with thrombophilia, were studied. Using variance component methods, implemented in the SOLAR package, the heritability of the following sets of platelet-related phenotypes was determined: platelet count and indices, IPF, and platelet function. RESULTS AND CONCLUSIONS: High heritabilities of the platelet count and index phenotypes (from 0.41 to 0.64) were found, especially for those related to platelet volume. The heritabilities of the IPF phenotypes, as a measure of platelet turnover, were the highest (from 0.65 to 0.69). The heritabilities of the platelet function phenotypes were high also (0.45 and 0.62). The covariate age influenced all of the platelet phenotypes. Smoking influenced the platelet indices related to platelet volume and all the IPF phenotypes. Venous thrombosis showed a heritability of 0.67. We did not find a genetic correlation between any of the platelet-related phenotypes and venous thrombosis. The high heritabilities found for all of the platelet phenotypes provid promising data for the identification of new genes that underly these phenotypes. PMID- 26148566 TI - A versatile snap chip for high-density sub-nanoliter chip-to-chip reagent transfer. AB - The coordinated delivery of minute amounts of different reagents is important for microfluidics and microarrays, but is dependent on advanced equipment such as microarrayers. Previously, we developed the snap chip for the direct transfer of reagents, thus realizing fluidic operations by only manipulating microscope slides. However, owing to the misalignment between arrays spotted on different slides, millimeter spacing was needed between spots and the array density was limited. In this work, we have developed a novel double transfer method and have transferred 625 spots cm(-2), corresponding to >10000 spots for a standard microscope slide. A user-friendly snapping system was manufactured to make liquid handling straightforward. Misalignment, which for direct transfer ranged from 150 250 MUm, was reduced to <40 MUm for double transfer. The snap chip was used to quantify 50 proteins in 16 samples simultaneously, yielding limits of detection in the pg/mL range for 35 proteins. The versatility of the snap chip is illustrated with a 4-plex homogenous enzyme inhibition assay analyzing 128 conditions with precise timing. The versatility and high density of the snap chip with double transfer allows for the development of high throughput reagent transfer protocols compatible with a variety of applications. PMID- 26148567 TI - Major perioperative complications after spine surgery in patients with cerebral palsy: assessment of risk factors. AB - PURPOSE: A prospective, longitudinal cohort was studied to determine the incidence, consequences, and risk factors of major perioperative complications in patients with cerebral palsy (CP) treated with spinal fusion. There is a wide variety of data available on the complications of spine surgery; however, little exists on the perioperative complications in patients with CP. METHODS: A prospective multicenter dataset of consecutive patients with CP treated with spinal fusion was evaluated. All major perioperative complications were identified and stratified into categories: pulmonary, gastrointestinal, other medical, wound infection, neurological, instrumentation related, and unplanned staged surgery. Univariate and multivariate analyses were performed to identify various risk factors for major perioperative complications. RESULTS: 127 patients were identified with a mean age of 14.3 +/- 2.6 years. Overall, 39.4% of the patients had a major perioperative complication. Occurrence of a complication [no complication (NC), yes complication (YC)] resulted in significantly increased intensive care unit (ICU) (NC = 3.2 days, YC = 7.8 days, p < 0.05) and hospital stays (NC = 7.7 days, YC = 15.6 days, p < 0.05). Variables associated with greater risk of a complication included: increased estimated blood loss (EBL) (p < 0.001), larger preoperative kyphosis (p = 0.05), staged procedures (p < 0.05), a lack of antifibrinolytic use (p < 0.05), and a trend toward lower body mass index (BMI) (p = 0.08). Multivariate regression analysis revealed an increased EBL as independently associated with a major perioperative complication (p < 0.05). CONCLUSIONS: In this cohort of patients with CP who underwent spinal fusion, 39.4% experienced a major perioperative complication, with pulmonary being the most common. The occurrence of a major perioperative complication lengthened both ICU and hospital stay. Risk factors for major perioperative complications included greater preoperative kyphosis, staged procedures, a lack of antifibrinolytic use, and increased EBL, with the latter being an independent predictor of a major perioperative complication. LEVEL OF EVIDENCE: 2. PMID- 26148568 TI - Functional consequences and health-care seeking behaviour for recurrent non specific low back pain in Zimbabwean adolescents: a cross-sectional study. AB - PURPOSE: The purpose of the study was to investigate the consequences of recurrent non-specific low back pain in Zimbabwean adolescents. Recurrent non specific low back pain is a common cause of adult disability in low-income countries. However, its impact in adolescents has been a matter of debate in the literature. METHODS: A survey was conducted using a cluster sample of 544 school children between the ages of 13 and 19 years. The school children were randomly selected from government-administered secondary schools in Harare, Zimbabwe. RESULTS: Parental and students' response rate were 90.3 and 97.8 %, respectively. Almost a third (28.8 %) of school children reported recurrent symptoms (CI 27.8 31.6). However, the majority (84 %) of these cases were unknown to parents. Twenty-seven percent reported having sought medical treatment. On the nine-item Hanover Low Back Pain Disability Questionnaire, 71.2 % of school children had at least one activity of daily living compromised by recurrent NSLBP, especially sports participation. However, severe disability was reported in 28 % of the adolescents. Health-care seeking behaviour was not associated with the level of disability [chi (2)(1) = 0.36, p = 0.55]. CONCLUSION: Although most parents are unaware, recurrent NSLBP is common in Zimbabwean school children. However, treatment is rarely sought for the symptoms. A preponderance of adolescents with recurrent NSLBP experiences some degree of functional consequences, although severe disability is rare. There is need to raise awareness of the condition in schools and to parents. Spinal health educational programmes may need to be implemented to avert the functional consequences. Further studies are needed in the future to investigate the coping strategies for pain in adolescents. PMID- 26148569 TI - A graphene based tunable terahertz sensor with double Fano resonances. AB - We propose an ultrasensitive terahertz (THz) sensor consisting of a subwavelength graphene disk and an annular gold ring within a unit cell. The interference between the resonances arising from the graphene disk and the gold ring gives rise to Fano type resonances and enables ultrasensitive sensing. Our full wave electromagnetic simulations show frequency sensitivity as high as 1.9082 THz per refractive index unit (RIU) and a figure of merit (FOM) of 6.5662. Furthermore, the sensing range can be actively tuned by adjusting the Fermi level of graphene. PMID- 26148570 TI - Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells. AB - The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus. PMID- 26148571 TI - EphB1 and EphB2 intracellular domains regulate the formation of the corpus callosum and anterior commissure. AB - The two cortical hemispheres of the mammalian forebrain are interconnected by major white matter tracts, including the corpus callosum (CC) and the posterior branch of the anterior commissure (ACp), that bridge the telencephalic midline. We show here that the intracellular signaling domains of the EphB1 and EphB2 receptors are critical for formation of both the ACp and CC. We observe partial and complete agenesis of the corpus callosum, as well as highly penetrant ACp misprojection phenotypes in truncated EphB1/2 mice that lack intracellular signaling domains. Consistent with the roles for these receptors in formation of the CC and ACp, we detect expression of these receptors in multiple brain regions associated with the formation of these forebrain structures. Taken together, our findings suggest that a combination of forward and reverse EphB1/2 receptor mediated signaling contribute to ACp and CC axon guidance. PMID- 26148572 TI - Pathological complete response to gefitinib in a 10-year-old boy with EGFR negative pulmonary mucoepidermoid carcinoma: a case report and literature review. AB - BACKGROUND AND AIMS: Pulmonary Mucoepidermoid carcinoma (MEC) accounts for 0.1 0.2% of all lung cancer. It occurred in the 3-78 years old, and 50% patients younger than 30. MEC has no standard treatment, but recently reports indicated MEC without epidermal growth factor receptor (EGFR) mutations sensitive to gefitinib. OBJECTIVES: To explore a new standard treatment strategy for MEC, after reviewed literature related to MEC, we used Gefitinib to treatment a patient with EGFR-negative MEC, and observe its effects. METHODS: 10-year-old boy was diagnosed with low-grade MEC by bronchial lung biopsy, EGFR gene mutation test was negative. Gefitinib was administered as neoadjuvant therapy at 125 mg daily. RESULTS: The patient underwent right middle lobe, lower lobe resection and mediastinal lymph node dissection. After surgery, the patient had gained weight (5 kg) after 18 days of gefitinib therapy. A CT scan of the chest 1 month after surgical resection showed no recurrence, and followed for 22 months after treatment without tumour recurrence, suggesting that the patient was completely cured. CONCLUSION: Gefitinib has potential to become a standard treatment for pulmonary MEC patients, including pediatric patients. However, the mechanisms need further investigation. PMID- 26148573 TI - The effect of colostrum period management on BW and immune system in lambs: from birth to weaning. AB - The aim of this study was to investigate the BW and immune status of lambs reared under natural conditions or under artificial conditions fed two different colostrum amounts. In this study, 60 lambs were randomly divided into groups according to treatment. Twenty lambs remained with their dams (natural rearing (NR) group). Forty lambs were removed from their dams at birth. Lambs were bottle fed with a pool of sheep colostrum, receiving either 4 g of IgG/kg of BW at birth (C4 group) or 8 g of IgG/kg of BW at birth (C8 group). The total colostrum amount was equally divided into three meals at 2, 14 and 24 h after birth. After this period, lambs were bottle-fed a commercial milk replacer. Blood plasma sample analysis and BW recordings were carried out before feeding at birth and then at 1, 2, 3, 4, 5 and 20 days after birth. Another blood sample analysis and BW recording was carried out when animals reached 10 kg of BW. During weaning (30 days), sampling was carried out every 5 days. Blood plasma was used to determine the concentrations of IgG and IgM and the complement system activity - total and alternative pathways. The NR group showed greater BW than the C4 and C8 groups during milk feeding period, whereas the C4 and C8 groups had greater BW than the NR group at the end of weaning period. The C8 and NR groups had greater plasma IgG and IgM concentrations than the C4 group during milk feeding period. In addition, C4 and C8 groups showed similar IgG concentrations and greater IgM concentrations than the NR group at the end of the weaning period. Complement system activity was greater in the NR group than in the C4 and C8 groups during the first 3 days after birth. In conclusion, lambs fed amounts of colostrum equivalent to 8 g of IgG/kg of BW showed similar immune variables compared to lambs reared under natural conditions, obtaining a greater BW at the end of the weaning period. Nevertheless, this study shows that not only the colostrum amount but also the management during the milk feeding and weaning period, such as stress produced by dam separation, milk quality and suckling frequency, can affect the final immune status of lambs. PMID- 26148574 TI - Glycerophospholipid synthesis and functions in Pseudomonas. AB - The genus Pseudomonas is one of the most heterogeneous groups of eubacteria, presents in all major natural environments and in wide range of associations with plants and animals. The wide distribution of these bacteria is due to the use of specific mechanisms to adapt to environmental modifications. Generally, bacterial adaptation is only considered under the aspect of genes and protein expression, but lipids also play a pivotal role in bacterial functioning and homeostasis. This review resumes the mechanisms and regulations of pseudomonal glycerophospholipid synthesis, and the roles of glycerophospholipids in bacterial metabolism and homeostasis. Recently discovered specific pathways of P. aeruginosa lipid synthesis indicate the lineage dependent mechanisms of fatty acids homeostasis. Pseudomonas glycerophospholipids ensure structure functions and play important roles in bacterial adaptation to environmental modifications. The lipidome of Pseudomonas contains a typical eukaryotic glycerophospholipid- phosphatidylcholine -, which is involved in bacteria-host interactions. The ability of Pseudomonas to exploit eukaryotic lipids shows specific and original strategies developed by these microorganisms to succeed in their infectious process. All compiled data provide the demonstration of the importance of studying the Pseudomonas lipidome to inhibit the infectious potential of these highly versatile germs. PMID- 26148575 TI - Generation of 3D shape, density, cortical thickness and finite element mesh of proximal femur from a DXA image. AB - Areal bone mineral density (aBMD), as measured by dual-energy X-ray absorptiometry (DXA), predicts hip fracture risk only moderately. Simulation of bone mechanics based on DXA imaging of the proximal femur, may help to improve the prediction accuracy. Therefore, we collected three (1-3) image sets, including CT images and DXA images of 34 proximal cadaver femurs (set 1, including 30 males, 4 females), 35 clinical patient CT images of the hip (set 2, including 27 males, 8 females) and both CT and DXA images of clinical patients (set 3, including 12 female patients). All CT images were segmented manually and landmarks were placed on both femurs and pelvises. Two separate statistical appearance models (SAMs) were built using the CT images of the femurs and pelvises in sets 1 and 2, respectively. The 3D shape of the femur was reconstructed from the DXA image by matching the SAMs with the DXA images. The orientation and modes of variation of the SAMs were adjusted to minimize the sum of the absolute differences between the projection of the SAMs and a DXA image. The mesh quality and the location of the SAMs with respect to the manually placed control points on the DXA image were used as additional constraints. Then, finite element (FE) models were built from the reconstructed shapes. Mean point-to surface distance between the reconstructed shape and CT image was 1.0 mm for cadaver femurs in set 1 (leave-one-out test) and 1.4 mm for clinical subjects in set 3. The reconstructed volumetric BMD showed a mean absolute difference of 140 and 185 mg/cm(3) for set 1 and set 3 respectively. The generation of the SAM and the limitation of using only one 2D image were found to be the most significant sources of errors in the shape reconstruction. The noise in the DXA images had only small effect on the accuracy of the shape reconstruction. DXA-based FE simulation was able to explain 85% of the CT-predicted strength of the femur in stance loading. The present method can be used to accurately reconstruct the 3D shape and internal density of the femur from 2D DXA images. This may help to derive new information from clinical DXA images by producing patient-specific FE models for mechanical simulation of femoral bone mechanics. PMID- 26148576 TI - Useful surface parameters for biomaterial discrimination. AB - Topographical features of biomaterials' surfaces are determinant when addressing their application site. Unfortunately up to date there has not been an agreement regarding which surface parameters are more representative in discriminating between materials. Discs (n = 16) of different currently used materials for implant prostheses fabrication, such as cast cobalt-chrome, direct laser metal soldered (DLMS) cobalt-chrome, titanium grade V, zirconia (Y-TZP), E-glass fiber reinforced composite and polyetheretherketone (PEEK) were manufactured. Nanoscale topographical surface roughness parameters generated by atomic force microscopy (AFM), microscale surface roughness parameters obtained by white light interferometry (WLI) and water angle values obtained by the sessile-water-drop method were analyzed in order to assess which parameter provides the best optimum surface characterization method. Correlations between nanoroughness, microroughness, and hydrophobicity data were performed to achieve the best parameters giving the highest discriminatory power. A subset of six parameters for surface characterization were proposed. AFM and WLI techniques gave complementary information. Wettability did not correlate with any of the nanoroughness parameters while it however showed a weak correlation with microroughness parameters. PMID- 26148577 TI - One-Pot Hydrothermal Synthesis of FeMoO4 Nanocubes as an Anode Material for Lithium-Ion Batteries with Excellent Electrochemical Performance. AB - Metal molybdates nanostructures hold great promise as high-performance electrode materials for next-generation lithium-ion batteries. In this work, the facial design and synthesis of monodisperse FeMoO4 nanocubes with the edge lengths of about 100 nm have been successfully prepared and present as a novel anode material for highly efficient and reversible lithium storage. Well-defined single crystalline FeMoO4 with high uniformity are first obtained as nanosheets and then self-aggregated into nanocubes. The morphology of the product is largely controlled by the experimental parameters, such as the reaction temperature and time, the ratio of reactant, the solution viscosity, etc. The molybdate nanostructure would effectively promote the insertion of lithium ions and withstand volume variation upon prolonged charge/discharge cycling. As a result, the FeMoO4 nanocubes exhibit high reversible capacities of 926 mAh g(-1) after 80 cycles at a current density of 100 mA g(-1) and remarkable rate performance, which indicate that the FeMoO4 nanocubes are promising materials for high-power lithium-ion battery applications. PMID- 26148578 TI - Travails of the terminally ill and dying with cancer. PMID- 26148579 TI - Living well till death. PMID- 26148580 TI - Hypofractionated radiotherapy in carcinoma breast: What we have achieved? AB - Healthy breast tissue is sensitive to radiation fraction size, such that small changes in fraction size can lead to larger changes in radiation effects on these tissues. Conventional breast and/or chest wall irradiation uses 2 Gy daily fractions, for 5-6 weeks. Such a long treatment schedule has major implications on both patient quality of life and burden of radiotherapy (RT) departments. Some investigators have hypothesized that breast cancer is as sensitive as normal breast tissue to fraction size. According to the hypothesis, small fraction sizes of 2.0 Gy or less offer no therapeutic advantage, and a more effective strategy would be to deliver fewer, larger fractions that result in a lower total radiation dose. This short (hypofractionated) RT schedule would be more convenient for patients (especially those coming from remote areas to RT facilities) and for healthcare providers, as it would increase the turnover in RT departments. This thought has prompted us to write a systematic review on role of hypofractionated RT in breast cancer in a developing country like ours where patient burden is an alarming problem. PMID- 26148581 TI - Prognostic role of pathologic fracture in osteosarcoma: Evidence based on 1,677 subjects. AB - INTRODUCTION: The prognostic role of pathologic fracture in osteosarcoma has not been settled down, as previous researches have reached contradictory results. This study is prepared to clarify whether pathologic fracture predicts a poor prognosis of patients with osteosarcoma. MATERIALS AND METHODS: After completely retrieved databases including China National Knowledge Infrastructure (CNKI), PubMed, Highwire, EMBASE and Science Direct, all eligible articles were included based on inclusion/exclusion criteria. And we performed a meta-analysis to calculate the pooled prognostic role of pathologic fracture in osteosarcoma. RESULTS: Finally, a total of 8 articles met the inclusion/exclusion criteria, involving 1,677 subjects. We found that the pooled hazard ratios (HRs) with 95% confidential interval (CI) of pathologic fracture in osteosarcoma for overall survival (OS) and disease-free survival (DFS) are 2.13 (1.43, 3.15) and 1.58 (1.11, 2.24), respectively. CONCLUSION: This meta-analysis demonstrated that presentation with a pathologic fracture in osteosarcoma was correlated with a poor prognosis. And pathologic fracture might be a poor predictor of survival in osteosarcoma. PMID- 26148582 TI - The efficacy of delayed surgery in children with high-risk neuroblastoma. AB - CONTEXT: Surgery is an important part of treatment in children with neuroblastoma; however, exact timing is unclear. Both initial and delayed surgery was suggested as the best by numerous studies. AIMS: Thus, we aimed to investigate the role of delayed surgery on 31 children with high-risk neuroblastoma. MATERIALS AND METHODS: Thirty-one children with high-risk neuroblastoma were enrolled into the study. STATISTICAL ANALYSIS USED: Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) for windows 10.0. RESULTS: There 'were 15 male and 16 female patients with a median age of 3.0 +/- 3.2 years. Primary tumor site was adrenal in 27, non-adrenal in two, pelvic in one, and mediastinal in one patient. MYCN gene was amplified in four and non-amplified in 11 children on totally 15 children with available data. Lactate dehydrogenase was elevated in 30 children. The tumor volumes at diagnosis and before surgery in the whole group were 154.3 and 12.5 mL, respectively. The decline in tumor volume was statistically significant (P < 0.0001). Initial surgery was performed in three and delayed in 20 children, and eight children were inoperable. Surgical complication rate was 66.6% (two out of three patients) in initial surgery group; however, the rate was 15% (3 out of 20 patients) in delayed surgery group. The 5-year event-free survival and overall survival rates in the whole group were 44.8% and 50.8%, respectively. Primary tumor area control rate was 95% CONCLUSIONS: In conclusion, the delayed surgery with intensive chemotherapy and radiotherapy has been successful for primary control in high-risk neuroblastoma patients. PMID- 26148583 TI - Histopathological evaluation of collagen fibers using picrosirius red stain and polarizing microscopy in oral squamous cell carcinoma. AB - BACKGROUND: Collagen is a part of structural connective tissue in every organ of the body. Study of collagen brings into focus the current knowledge of biosynthesis and degradation as a complex mechanism. One of the major aspects of tumor cell invasion and metastasis is the interaction between cancer cells and extracellular matrix component. Property of picrosirius red to enhance the birefringence is the result of basic protein nature of collagen molecules. There exists a direct relationship between the presence of type IV collagen and degree of differentiation in squamous cell carcinoma (SCC) cells as they lose their capability to form the basement membrane. MATERIALS AND METHODS: Thirty cases of oral SCC (OSCC) were evaluated for standard staining protocol of picrosirius red to analyze collagen fibers in different grades of OSCC under polarizing microscopy. RESULTS: In this study, moderately to poorly differentiated OSCC cases showed a gradual change in polarizing colors from yellowish orange to greenish yellow particularly in the vicinity of invading tumor islands. Thick collagen fibers forming bundles in parallel disposition were found around the neoplastic areas in discontinuous fashion. Type I collagen fibers of different lengths were strongly birefringent and swirl pattern, parallel orientation was evident. CONCLUSION: An observable stromal change with the progression of neoplasm was evinced with picrosirius red stain in different thickness of collagens with a significant change in the arrangement from the early stage to the advanced stage according to tumorogenesis. PMID- 26148584 TI - Expression of elastic fiber in esophageal squamous carcinoma tissue. AB - AIM: We studied the expression of elastic fiber in esophageal squamous cell carcinoma tissue in North-eastern Indian population. MATERIALS AND METHODS: Archival paraffin embedded 40 esophageal carcinoma specimens were retrieved for the study. Only smokers were included in the study. Verhoeff's stain for elastic fiber was performed to demonstrate elastic fiber with positive and negative control. RESULT: A total of 28 (70%) tissue specimens was found to be positive for elastic fiber. CONCLUSION: Elastosis in esophageal carcinoma may be due to smoking. Further studies are required to rule out the etiology. PMID- 26148585 TI - Analysis of various risk factors affecting potentially malignant disorders and oral cancer patients of Central India. AB - CONTEXT: The use of tobacco/betel quid can alone lead to death. India is the fourth largest consumer of tobacco/betel quid in the world and the third-largest producer of tobacco/betel quid after China and Brazil. AIMS: A case-control study was carried out to assess the prevalence and various risk factors among potentially malignant disorders (PMD) and oral cancer patients of central India. SETTINGS AND DESIGN: A total of 100 clinically and histopathologically diagnosed PMD and oral cancer patients were selected for the study. MATERIALS AND METHODS: A histopathologically confirmed 100 patients who were suffering from PMD and oral cancers were selected and an equal number 100 healthy controls who were age- and sex-matched at par with the cases were also examined and interviewed. Chi-square (chi(2)) test and adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated to estimate the suspected risk factors for PMD and oral cancers by using multivariate logistic regression analysis. Significance level was set at P < 0.05. RESULTS: Statistically significant difference was observed in the age group, socioeconomic status (SES), duration, frequency, exposure time and synergistic effect of tobacco/betel quid chewing, smoking, and alcohol drinking in our study population. CONCLUSIONS: Chewing tobacco/betel quid is a strong risk factor in the development of PMD and oral cancer. Also age, gender, SES, education, and occupation influence the development of PMD and oral cancer. PMID- 26148586 TI - Metronomic oral chemotherapy with old agents in patients with heavily treated metastatic breast cancer. AB - BACKGROUND: We aimed to assess the efficacy of a metronomic regimen with cyclophosphamide and etoposide in heavily treated patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: A total of 77 patients with MBC used continuous oral cyclophosphamide 50 mg/day and oral etoposide given as 2 * 50 mg/day for 2 days per week, were analyzed retrospectively from Akdeniz University and Selcuk University. The patients with MBC are predominantly refractory to antracyclines, taxanes, and antimetabolites. RESULTS: The patients were treated and followed between May 2005 and June 2014. The median progression-free and overall survival (PFS and OS) were 7.03 (5.06-8.99) and 32.5 (22.5-42.4) months, respectively. No prognostic factor was found for OS. CONCLUSIONS: Metronomic treatment regimen with cyclophosphamide and etoposide is a novel and effective strategy in heavily pretreated MBC patients. This regimen can be used in early or late steps as independently from prognostic factors. Moreover, it has very low toxicity and is cheap. Impressive survival data and low cost may make this regimen a highly preferable option. PMID- 26148587 TI - Efficacy of oxitard capsules in the treatment of oral submucous fibrosis. AB - AIM: Oral submucous fibrosis (OSMF) is a high-risk premalignant condition predominantly seen in the Indian subcontinent. The aim of the present study was to evaluate the efficacy of oxitard capsules in the management of OSMF. MATERIALS AND METHODS: Total of 120 subjects with clinico-pathologically diagnosed OSMF were included in the study and divided equally in 2 groups; Group A (oxitard group) and Group B (placebo group). Group A was administered 2 oxitard capsules twice daily and Group B was given placebo tablets twice daily, for 3 months. Evaluation for different clinical parameters was done at regular intervals and data was analyzed using the Student's paired t test and Chi-square test. P < 0.001 was considered to be statistically significant. RESULTS: Clinical improvements in mouth-opening and tongue protrusion were significant in the Group A (P < 0.001). Subjective symptoms of burning sensation (P = 0.0001), pain associated with the lesion (P = 0.000), difficulty in swallowing (P = 0.0003) and speech (P = 0.0005) also significantly improved in the Group A. There was a mild to moderate decrease in the size of the lesion. CONCLUSION: Though there is no definitive treatment for the condition; however, oxitard capsules can bring about significant clinical improvements in the symptoms like mouth-opening, tongue protrusion, burning sensation, difficulty in swallowing and speech and pain associated with the lesion, thereby improving the quality of life of the affected individuals. PMID- 26148588 TI - The expression difference of insulin-like growth factor 1 receptor in breast cancers with or without diabetes. AB - CONTEXT: The insulin-like growth factor (IGF) and insulin receptors' (IR) axes play important roles in both breast cancer and diabetes mellitus. AIM: We tend to explore the expression characteristics of proteins in IGF/IR axis in breast cancer with type 2 diabetes mellitus (T2DM). SETTINGS AND DESIGN: We conducted a case-control investigation of T2DM and non-diabetes (n = 40, 1:1) in breast cancer patients. MATERIALS AND METHODS: Some important molecules of IGF/IR axis were detected in breast cancer tissues by immunohistochemical staining. The multivariable analyses of the relationship of clinicopathological characters with the significant molecules were also detected. STATISTICAL ANALYSIS USED: The results were statistically evaluated by Statistical Package for the Social Sciences (SPSS version 17.0) software. Chi-square test and logistic regression are used. RESULTS: Higher expression of IGF 1 receptor (IGF1R) was found in breast cancers of patients with T2DM, compared those without diabetes (P = 0.044). Negative expression of human epidermal growth factor receptor 2 (Her2) was found to be associated with higher expression of IGF1R in the breast cancers of patients with T2DM. There were no differences found in the expression of proteins of IGF-1, IGF-2, IGF-binding protein 3 (IGFBP3), IR, insulin receptor substrate (IRS)-1, IRS-2 and mammalian target of rapamycin (mTOR) between T2DM group and non-diabetes group. CONCLUSION: Our study found that breast cancer with T2DM had a higher expression of IGF1R, and the higher IGF1R was associated with negative Her2 expression. PMID- 26148589 TI - Breast conservative therapy in Pakistani women: Prognostic factors for locoregional recurrence and overall survival. AB - OBJECTIVES: Breast conservative therapy (BCT) is an established method of treating early stage invasive breast cancer. Survival after BCT in Pakistani population has not been reported. This study was carried out to report locoregional control and overall survival (OS) after BCT for invasive breast cancer and analyze prognostic factors in Pakistani population. MATERIALS AND METHODS: Patients who received BCT between 1997 and 2009 were included in the study. Patients' follow-up, demographics, prognostic variables and treatment modalities were assessed. Data were analyzed for locoregional and distant relapse and estimated 10-year locoregional recurrence free survival (LRRFS) and OS was calculated using Kaplan Meier curves. To determine the significance of prognostic variables, univariate and multivariate analysis was performed. RESULTS: A total of 902 patients underwent BCT. Median age was 42 (17-82) years and the median follow-up was 51 (1.4-187) months. There were 484 (53.6) poorly differentiated and 194 (21.5) triple negative tumors. T3/T4 tumors were found in 128 (14.1) patients and 441 (44.8) patients had nodal involvement. Among adverse events, 58 (6.3) locoregional failures, 152 (16.8) distant failures and 155 (17.1) deaths were observed. Estimated 10 years LRRFS- was 88% while OS was 70%. On multivariate analysis, tumor size and nodal involvement were independent predictors of locoregional recurrence-free and OS. In addition, hormonal therapy significantly affected OS. CONCLUSION: BCT has acceptable long-term results in Pakistani women. Tumor size and nodal involvement are independent predictors of survival. PMID- 26148590 TI - Low titer of antibody against Toxoplasma gondii may be related to resistant to cancer. AB - CONTEXT: Toxoplasma gondii is a protozoan parasite with a world-wide distribution. However, the majority of infected cases remain symptomless. There are raising scientific evidences indicating that parasitic infections induce antitumor activity against certain types of cancers. The inhibitory effect of T. gondii on cancer growth has also been shown in cell culture and mouse model. AIMS: Considering the anti-tumor effect of this parasite, in this study the relationship between low titer of antibodies against T. gondii and resistant to cancers has been investigated. SUBJECTS AND METHODS: In two separate experiments, anti T. gondii antibody was estimated in 150 patients with cancer and 120 normal people. STATISTICAL ANALYSIS USED: Chi-square test was used for data analysis. RESULTS: The frequency of low titer antibody against Toxoplasma gondii in cancer patients was significantly higher than the frequency of low-titer antibody against this parasite in normal people. CONCLUSIONS: Exposure to T. gondii may be related to resistance to cancer. PMID- 26148591 TI - TIMP-2 G-418C polymorphism and cancer risk: A meta-analysis. AB - PURPOSE: Tissue inhibitor of metalloproteinase-2 (TIMP-2) plays a critical role in human carcinogenesis. However, the association between TIMP-2 G-418C polymorphism and risk of cancer was reported with inconclusive results. MATERIALS AND METHODS: A meta-analysis of 11 published studies involving 2,658 cases and 3,433 controls was performed to assess the strength of association using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The results indicated that no significant association between TIMP-2 G-418C polymorphism and cancer risk in overall population (GC vs. GG: OR = 1.26, 95% CI = 0.87-1.83; CC vs. GG: OR = 0.90, 95%CI = 0.50-1.63; GC/CC vs. GG: OR = 1.26, 95%CI = 0.87-1.82; C vs. G: OR = 1.19, 95%CI = 0.87-1.62). However, stratified analysis by ethnicity showed that TIMP-2 G-418C polymorphism was associated with cancer risk among Caucasian population (GC vs. GG: OR = 20.00, 95%CI = 9.90-40.38; GC/CC vs. GG: OR = 10.70, 95%CI = 1.11-103.20; C vs. G: OR = 14.98, 95%CI = 7.66-29.32) but not among Asian population. CONCLUSIONS: This meta-analysis suggests that TIMP-2 G 418C polymorphism may not influence the susceptibility of total cancer in overall population, but it was associated with cancer risk among Caucasian population. PMID- 26148592 TI - Adjuvant radiotherapy in stage 1 seminoma: Evaluation of prognostic factors and results of survival. AB - PURPOSE: The purpose of this study was to evaluate the prognostic factors affecting overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and survival among patients undergoing adjuvant radiotherapy (RT) for stage-1 seminoma. MATERIALS AND METHODS: Between August 1997 and May 2013, 68 patients diagnosed with stage-1 seminoma were retrospectively evaluated. The median age was 39 (24-74) years. All patients received adjuvant RT after inguinal orchiectomy. Fifty-eight (85.3%) patients received paraaortic RT; 10 (14.7%) received dog-leg field RT. The median RT dose was 23.4 (23.4-30.6) Gy. RESULTS: The median follow-up period was 77.5 (6.7-198.5) months. During the follow-up period, two patients developed distant metastasis, and none developed local recurrence. Two patients died from seminoma, and three died for other reasons. The 5, 10, and 15-year OS rates were 94.7%, 89.6%, and 89.6%, respectively. The 5, 10, and 15-year CSS rates were 98.5%, 96%, and 96%, respectively. The 5, 10, and 15-year PFS rate was 96.1%. The univariate analysis showed that only histological subtype was significant for OS. The 10-year survival rate was 100% among patients with seminoma histology, 90.8% among patients with a classic seminoma histology, and 50% among patients with an anaplastic seminoma histology (P < 0.001). A multivariate analysis showed that the anaplastic seminoma was a negative prognostic indicator for OS (P = 0.042). CONCLUSION: Adjuvant RT resulted in excellent long-term survival and local control in patients with stage 1 seminoma after orchiectomy. During a short follow-up, secondary malignancy (SM) and late cardiovascular morbidity were not observed. Despite those results, concern of SM and late cardiovascular morbidity remains. PMID- 26148593 TI - Expression of activating transcription factor 7 is correlated with prognosis of colorectal cancer. AB - BACKGROUND: It is important to identify some tumor-related factors for early detection, treatment, and evaluation of prognosis in colorectal cancer (CRC). In our study, we investigated the clinical and prognostic role of activating transcription factor 7 (ATF7) in CRC. MATERIALS AND METHODS: Expression of ATF7 was detected with immunohistochemistry in 72 cases with complete follow-up data and post-operation tissue specimens. Correlation between ATF7 and other clinicopathological factors was calculated with Chi-square test and the impact of ATF7 on survival were analyzed with Log-rank test and Cox regression models. RESULTS: Among 72 cases, ATF7 expression was detected in 43 cases (59.7%) and 29 cases (40.3%) without ATF7 expression. The correlation between ATF7 expression and pathological stage was investigated (P = 0.041). The 5-year overall survival (OS) of with or without ATF7 expression was 79% versus 51% respectively (P < 0.001) and the 5-year progression free survival (PFS) was 74% versus 41% (P < 0.001). The media OS was 69 months versus 52 months (P = 0.002) and the media PFS was 65 months versus 42 months (P = 0.002). ATF7 expression and numbers of lymph nodes involvement were prognostic factors for OS according to univariated and multivariated analysis and for PFS it was ATF7 expression and lymph nodes involvement. CONCLUSION: It is negatively related between ATF7 expression and pathological stage and positive correlation with OS and PFS in CRC. ATF7 expression is a favorable factor for survival of patients with CRC. PMID- 26148594 TI - Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice. AB - OBJECTIVE: This work was aimed at studying the inhibitory activity of metformin combined with the commonly used chemotherapy drug cisplatin in human lung cancer xenografts in nude mice. We also examined the combined effects of these drugs on the molecular expression of survivin, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor-C (VEGF-C), and vascular endothelial growth factor receptor-3 (VEGFR-3) to determine the mechanism of action and to explore the potential applications of the new effective drug therapy in lung cancer. MATERIALS AND METHODS: The nude mice model of lung cancer xenografts was established, and mice were randomly divided into the metformin group, the cisplatin group, the metformin + cisplatin group, and the control group. The animals were killed 42 days after drug administration, and the tumor tissues were then sampled to detect the messenger ribonucleic acid (mRNA) and protein expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the cisplatin group and the combined treatment group were lower than that in the control group (P < 0.05). In the metformin group, the expression of MMP-2 protein and mRNA was lower than that in the control group (P < 0.05). The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the combined treatment group were lower than that in the cisplatin group and the metformin group (P < 0.05). CONCLUSIONS: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy. PMID- 26148595 TI - Clinical study of tegafur-gimeracil-oteracil potassium capsule (s-1) and oxaliplatin combination chemotherapy in advanced colorectal cancer. AB - OBJECTIVE: The aim of this study was to evaluate the therapeutic efficacy and toxicity of a combination of tegafur-gimeracil-oteracil potassium capsules (S-1) with oxaliplatin for treatment of advanced or recurrent colorectal cancer. SUBJECTS AND METHODS: Between October 2009 and October 2011, 70 patients at our hospital with advanced or recurrent colorectal cancer were enrolled into our study and divided randomly into two groups: A treatment group (S-1 combined with oxaliplatin) and a control group (Xeloda combined with oxaliplatin). All patients received 130 mg/m(2) oxaliplatin by intravenous infusion on day 1, every three weeks. Patients in the treatment group were treated with oral administration of 30-40 mg/m(2) S-1 twice daily for 14 days. Patients in the control group were treated with oral administration of 1000 mg/m(2) Xeloda twice daily for 14 days. The efficacy and toxicity of the combination therapy were evaluated after two cycles of treatment. RESULTS: The response rates in the treatment and control groups were 54.3% and 42.9%, respectively. The disease control rates of the two groups were 80.0% and 74.3%, respectively. The 1-year and 2-year survival rates were 73.6% and 39.1% in the treatment group, respectively, compared to 73.8% and 37.8% in the control group. No statistical difference between the two groups for any of the parameters, including toxicity, was observed (P > 0.05). CONCLUSION: The efficacy of the S-1 and oxaliplatin combination regimen in advanced or recurrent colorectal cancer treatment is not inferior to the combination of Xeloda and oxaliplatin and does not result in additional toxicity. Therefore, S-1 could be used to substitute Xeloda in combined chemotherapy with oxaliplatin for the treatment of advanced or recurrent colorectal cancer. PMID- 26148596 TI - Sensitization to oxaliplatin in HCT116 and HT29 cell lines by metformin and ribavirin and differences in response to mitochondrial glutaminase inhibition. AB - AIM OF STUDY: In the present study, we evaluated the effect of ribavirin and metformin on the sensitivity of oxaliplatin and 5-fluorouracil (5-FU) on colon cancer. MATERIALS AND METHODS: Cell viability of two commercially available colon cancer cell lines (HT29 and HCT116) were analyzed by sulforhodamine B (SRB) assay. RESULTS: A clinically achievable and nontoxic concentration of ribavirin and metformin showed a significant synergistic effect on oxaliplatin in HT29 and HCT116 cell lines. Ribavirin showed a synergistic effect on oxaliplatin in HT29 (R = 2.93, P < 0.001) and HCT116 (R = 1.71, P < 0.001), while only in HT29 metformin synergized with oxaliplatin by 2.66 (+/- 0.28, P < 0.01). In addition, both cell lines showed significant differences in response to Compound 968, inhibitor of mitochondrial glutaminase activity. CONCLUSION: The data suggested that these cell lines not only turn to metabolic different sustainability process after oxaliplatin treatment but that they also have different basal metabolic requirements of glutamine in vitro which can be exploits in the future for colorectal cancer (CRC) treatment and further studies are required. PMID- 26148597 TI - Autoantibodies in the sera of breast cancer patients: Antinuclear and anti-double stranded DNA antibodies as example. AB - BACKGROUND: Inflammation and cell necrosis are one of the consequences that accompany breast cancer. However, inflammation and cell necrosis are well known to be involved in stimulation of cellular and humeral immunity. OBJECTIVES: The aim of this study is to investigate the immune response to the inflammation that accompanies cancer through measuring plasma concentration of antinuclear antibodies (ANAs) and anti-double stranded deoxyribonucleic acid antibodies (ADSDAs). MATERIALS AND METHODS: Thirty-five newly diagnosed breast cancer patients were involved in this study from the Radiation Isotopes Center Khartoum (RICK) compared to 18 age- and sex-matched control subjects. Intravenous blood sample was obtained from each study subject and Enzyme Linked Immuno Sorbent Assay (ELISA) technique was used to determine the concentration of the two antibodies. RESULTS: Regarding the ANA concentration in the patients; the range was 0.7-1.8 IU/ml, mean was 0.96, and the standard deviation (SD) was 0.25; while the range of the concentration in the control subjects was 0.3-0.6 IU/ml, mean was 0.47, and SD was 0.07. However, when the means of patients and controls were compared, the difference was significant (P < 0.000). Concerning the result anti double stranded DNA (anti-dsDNA), its concentration range in the patients was 2.6 151.9 IU/ml, the mean was 55.2, and SD was 25.6, while in healthy people concentration range was 26.1-97.3 IU/ml, the mean was 50.3, and SD was 16.9. There was no significant change between the patients and controls (P = 0.46). CONCLUSION: The ANA concentration in the patients was significantly increased, while there was no significant difference between the results of ADSDAs in the patients and the control subjects. PMID- 26148598 TI - Sensitivity of endometrial cancer cells from primary human tumor samples to new potential anticancer peptide lactaptin. AB - PURPOSE: Endometrial carcinoma is the most common gynecologic malignancy which is associated with a poor prognosis when diagnosed at an advanced stage; therefore, the discovery of efficacious new drugs is required to reinforce conventional chemotherapy. Short-term cultures of primary cells from endometrial tumors could be used for testing new anticancer therapeutics as well as for the development of personalized cancer therapy strategy. Here, the antitumor effect of a recombinant analogue of lactaptin (RL2), a new potential anticancer molecule, was examined against primary human endometrial cancer cells. MATERIALS AND METHODS: Primary cell cultures of malignant and normal human endometrium were performed by enzymatic digestion of endometrial tissue from biopsy material. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the messenger ribonucleic acid (mRNA) state of estrogen (ERs) and progesterone (PRs) hormone receptors and aromatase (Cyp 19) in cell cultures. Dynamic monitoring of cell adhesion and proliferation was made using the iCELLigence system (ASEA Biosciences). The sensitivity of cell cultures to conventional anticancer drugs and the lactaptin analog was estimated by 3-(4,5 dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry, and the iCELLligence system. RESULTS: Established short-term primary cultures of endometrial cancer cells were ERalpha/ERbeta/PR-positive and sensitive for RL2. The IC 50 values of doxorubicin and cisplatin were determined for all of the primary cultures designed. KE normal cells displaying low Cyp19 mRNA levels and high ERbeta and PR mRNA levels were more resistant to RL2 treatment as well as to cisplatin and doxorubicin. CONCLUSIONS: Our results indicate that the recombinant analog of lactaptin, RL2, exerts cytotoxic effects against primary hormone-dependent endometrial tumor cells in vitro with features of apoptosis. PMID- 26148599 TI - Enhancement of the cytotoxic effects of Cytarabine in synergism with Hesperidine and Silibinin in Acute Myeloid Leukemia: An in-vitro approach. AB - OBJECTIVES: Acute Myeloid Leukemia (AML) therapy continues to be a daunting challenge. Cytosine Arabinoside (Ara-C) is widely used to treat hematological malignancy in humans, but often becomes ineffective because of increased resistance to the drug which may lead to a worse prognosis. Therefore new strategies are needed to understand the mechanism responsible for drug resistance and to develop new therapies to overcome it. Research evidence based on natural compounds used alone or in combination with current chemotherapeutic agents proved their efficacy to treat and prevent cancer. Hesperidin and Silibinin displayed anti-cancer activity against various types of cancers and cell lines and can be used in combination with Cytarabine with the aim to increase cytotoxicy profile and reduction in drug resistance. Experimental Work: Primary cells obtained from AML patient's bone marrow were used to develop in-vitro model and further exposed to various concentration of Cytarabine (10 nM-5000 nM), Hesperidin (0.5 MUM-100 MUM) and Silibinin (0.5 MUM-100 MUM) alone and in combination with Cytarabine (Hesperidin-25 MUM, Silibinin10 MUM) to check cytotoxicity using MTT assay. Synergistic effect was evaluated by Combination Index method. RESULT AND CONCLUSION: In-vitro study of Hesperidin and Silibinin indicated their cytotoxicity at IC 50 value 50.12 MUM and 16.2 MUM, respectively. Combination Index study revealed Hesperidin and Silibinin both showed synergistic potential and decreased the IC 50 value of Cytarabine by ~5.9 and ~4.5 folds, respectively. Both natural compounds showed potential anti-leukemic activity hence may be used for AML therapy alone or in combination with other chemotherapeutic agents. PMID- 26148600 TI - Which is the most optimal technique to spare hippocampus?-Dosimetric comparisons of SCRT, IMRT, and tomotherapy. AB - AIMS: To evaluate current focal high precision radiotherapy (RT) techniques to spare hippocampi most optimally, in view of mounting clinical evidence to preserve neurocognition. MATERIALS AND METHODS: Computed tomography/magnetic resonance imaging (CT/MRI) datasets of 10 patients with benign/low-grade brain tumors, treated with focal conformal RT were replanned with helical tomotherapy (Tomo), intensity-modulated radiotherapy (IMRT) with high definition multileaf collimator (HD-MLC), and forward planning stereotactic conformal radiotherapy (SCRT). The primary planning objective was to encompass 99% of planning target volume (PTV) by 95% of prescribed dose (54 Gy/30#). Assessments included target coverage (TC), homogeneity index (HI), and maximum (max) and minimum (min) dose. Hippocampal dose was assessed with mean, maximum, minimum, median dosem and various dose levels. RESULTS: Mean V 95 for PTV coverage in Tomo, IMRT, and SCRT were 99.7, 99.4, and 98.3%, respectively. PTV coverage was significantly better in Tomo and IMRT compared to SCRT (P = 0.03). Tomotherapy (HI <= 0.06) and IMRT (HI <= 0.06) plans were more homogenous than SCRT (HI > 0.7) (P = 0.00). Right hippocampus mean dose with Tomo (20Gy) was 18.5% less than SCRT (30 Gy); but for left hippocampus, difference decreased to 3.3% (Tomo-32.2Gy and SCRT-34Gy). At 30% dose level, 9% more volume of right hippocampus was treated in IMRT and 20% in SCRT when compared to Tomo plan. At 80% dose, 6 and 12% more volumes were treated with IMRT and SCRT, respectively, in comparison to Tomo plan. For left hippocampus all three techniques were comparable. CONCLUSION: Tomotherapy and Linear accelerator (LINAC)-based IMRT achieved significantly better PTV coverage than forward planned SCRT. Tomo as compared to SCRT and IMRT plans showed trend towards significant sparing of the contralateral hippocampus, in eccentrically located tumors. PMID- 26148601 TI - Prediction of outcome in buccal cancers treated with radical radiotherapy based on the early tumor response. AB - AIM OF THE STUDY: Aim was to assess the clinical significance of the rate of tumor regression in carcinoma buccal mucosa undergoing radical radiotherapy. MATERIALS AND METHODS: Sixty six patients were enrolled in the study with proven buccal cancers requiring radical radiotherapy, from 1990 to 1996. Radiotherapy was delivered using a combination of external beam and brachytherapy with preloaded cesium 137 needles. The response to the radiation was assessed at the completion of external beam radiation and 6 weeks after brachytherapy. An analysis correlating various parameters influencing the long term disease free survival and overall survival was done. RESULTS: Response assessed at the end of external beam radiation correlated strongly with the overall survival and the disease free interval (P=0.000). No other factor influenced the survival. CONCLUSION: The rate of the tumor regression can predict the overall outcome in patients with buccal cancers treated with radiation. Completion of the planned course of radiation in patients who do not show a substantial reduction in size by 4.5 weeks of conventional radiation does not improve the results. PMID- 26148602 TI - Adjuvant chemoradiation versus chemotherapy for stage III gastric cancer after surgery with curative intent. AB - OBJECTIVE: Gastric cancer is often diagnosed at an advanced stage and surgery alone cannot guarantee satisfactory results. Both chemoradiotherapy (CRT) and chemotherapy (CT) are used in postoperative therapy. However, it is controversial whether CRT or CT is better after D2 lymphadenectomy. In this study we investigated the efficacy of adjuvant CRT versus CT in stage III gastric cancer patients treated with R0 gastrectomy and D2 lymph node dissection. PATIENTS AND METHODS: Data from 92 patients diagnosed with gastric adenocarcinoma and treated with surgery followed by adjuvant treatment were retrospectively analyzed. Patients were classified into two groups depending on type of adjuvant treatment such as CT (Arm A) and CRT (Arm B). RESULTS: Twenty-one patients in Arm A and 71 patients in Arm B were included. Median age at diagnosis was 60 years. The median follow-up time was 30 months. No difference in local recurrence (14.3 vs 15.7%, P = 0.89), peritoneal recurrence (29.4 vs 23.5%, P = 0.62), and distant metastases rates (57.1 vs 45.1%, P = 0.42) were observed between the arms. Disease-free survival (DFS) rates did not differ between Arms A and B (26 and 22 months, P = 0.80) respectively. Median overall survival (OS) in Arm A was 29 months and it was 32 months for Arm B. There was no difference in 5-year OS and DFS between Arms A and B (23.8 vs 34.4%, P = 0.74; and 24.1 vs 32.9%, P = 0.80). CONCLUSIONS: Adjuvant CRT does not appear to improve clinical outcomes compared to adjuvant CT in this study and prospective studies are required to confirm these results. PMID- 26148603 TI - Clinical significance of plasma lysophosphatidic acid levels in the differential diagnosis of ovarian cancer. AB - OBJECTIVE: To investigate the value of lysophosphatidic acid (LPA) in the diagnosis of ovarian cancer. MATERIALS AND METHODS: We first performed a hospital based, case-control study involving 123 ovarian cancer patients and 101 benign ovarian tumor patients, and then conducted a meta-analysis with 19 case-control studies to assess the correlation between ovarian cancer and plasma LPA levels. RESULTS: The case-control study results demonstrated that ovarian cancer patients have increased LPA and cancer antigen (CA)-125 levels compared to patients with benign ovarian tumor (LPA: Ovarian cancer vs benign ovarian tumor: 5.28 +/- 1.52 vs 1.82 +/- 0.77 MUmol/L; CA-125: Ovarian cancer vs benign ovarian tumor: 87.17 +/- 45.81 vs. 14.03 +/- 10.14 U/mL), which showed statistically significant differences (both P < 0.05). LPA with advanced sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate of diagnosis excelled CA-125 in the diagnosis of ovarian cancer (both P < 0.05). The areas under the receiver operating characteristic (ROC) curve in the diagnosis of ovarian cancer (LPA: 0.983; CA-125: 0.910) were statistically significant compared with the reference (both P < 0.001) and the difference of the areas of ROC curve between LPA and CA-125 in the diagnosis of ovarian cancer showed statistically significant difference (P < 0.05). The meta-analysis results suggested that plasma LPA levels were higher in ovarian cancer tissues than in benign tissues (standardized mean difference (SMD) =2.36, 95% confidence interval (CI): 1.61-3.11, P < 0.001) and normal tissues (SMD = 2.32, 95% CI: 1.77-2.87, P < 0.001). CONCLUSION: LPA shows greater value in the diagnosis of ovarian cancer compared to CA-125 and may be employed as a biological index to diagnose ovarian cancer. PMID- 26148604 TI - Prospective study of special stage II (T2b-3N0M0) non-small-cell lung cancer treated with hypofractionated-simultaneous integrated boost-intensity modulated radiation therapy. AB - PURPOSE: To analyze the effects of hypofractionated-simultaneous integrated boost intensity modulated radiation therapy (Hypo-SIB-IMRT) on medically inoperable patients with special stage II (T2b-3N0M0) non-smallcell lung cancer (NSCLC). MATERIALS AND METHODS: Twenty-eight qualified patients were included. Hypo-SIB IMRT was delivered with internal gross tumor volume (iGTV) 75 Gy, clinical target volume (CTV) 60 Gy, and planning target volume (PTV) 45 Gy on weekdays in 3 weeks. RESULTS: The 1-, 2-, and 3-year overall survivals (OSs) were 93, 85, and 61%, respectively, with a median survival of 46.5 months; while progression-free survivals (PFSs) were 92, 79, and 64%; and distant metastasis-free survivals (DMFSs) were 92, 84, and 77%, respectively. The cancer-specific survivals (CSS) were 93, 88, and 74%, and local control (LC) were 92, 83, and 74%, respectively. 7.1% (2/28) of patients occurred local pain, 28.6% (8/28) were with Grade 1 or 2 radiation pneumonitis (RP), and 7.1% (2/28) with Grade 1 esophagitis. Of the eight patients with RP, 17.9% (5/28) developed Grade 1 radiation pulmonary fibrosis (RPF). CONCLUSION: Due to the favorable long-term survivals, LC, and minimal toxicities, Hypo-SIB-IMRT presented in this prospective study may be considered an option for patients with special stage II (T2b-3N0M0) NSCLC who were medically inoperable. PMID- 26148605 TI - First experience of Candida non-albicans isolates with high antibiotic resistance pattern caused oropharyngeal candidiasis among cancer patients. AB - BACKGROUND AND AIM: In cancer patients, Candida species can cause a variety of diseases particularly oropharyngeal candidiasis which is a common infection. In this study, an attempt has been made to determine susceptibility pattern of four antifungal agents against the Candida species isolated from cancer patients with oropharyngeal candidiasis. MATERIALS AND METHODS: Samples were taken from 50 cancer patients with oropharyngeal candidiasis by the physician, and isolation and identification of Candida spp. was done based on standard procedures. Antifungal resistance pattern was carried out according to CLSI guidelines, and 18s ribosomal RNA among Candida spp. was identified using multiplex polymerase chain reaction. RESULTS: Of the 50 patients, 18 (36%) were females and 32 (64%) were males; mean age was 38.4 years. Leukemia and lymphoma were the most frequent cancer types in the studied group, accounting for 17 (34%) and 12 (24%), respectively. A total of 29 Candida spp. were isolated from 29 cancer patients, of which 17 were C. albicans and 12 were C. non-albicans. All the Candida spp. were confirmed having 18s ribosomal RNA. Among all the Candida spp., C. non albicans showed higher resistance pattern to amphotericin B (MIC 07 MUg/ml) and ketoconazole (MIC = 05 MUg/ml). CONCLUSION: In conclusion, oropharyngeal Candidiasis is a serious infection among cancer patients. The isolated Candida spp. were resistant to common antifungal agents, which may lead to longer hospital stay, more expensive/toxic drugs and higher mortality. Therefore, interval surveillance is necessary in developing institutional guidelines. PMID- 26148606 TI - Feasibility of PET-CT based hypofractionated accelerated dose escalation in oropharyngeal cancers: Final dosimetric results of the VORTIGERN study. (Secondary endpoint of UK NCRI portfolio: MREC No: 08/H0907/127, UKCRN ID 7341). AB - OBJECTIVE: Technological advances have enabled clinicians to explore dose escalation strategies in various tumor sites. Intermediate and high risk oropharyngeal cancers have poor 5 year outcomes. This study aimed to assess the feasibility and dosimetric safety of 9% dose escalation in these tumors and compare the dose received by organs at risk (OAR) in escalated plans (67.2 Gy/28 fractions) versus (65 Gy/30 fractions) standard dose plans. MATERIALS AND METHODS: FDG-PET fused datasets were used to delineate gross, clinical and planning target volumes. Standard dose plans were created using two non IMRT techniques (conventional and field in field plans) whilst the patient was treated using a helical tomotherapy plan. A fourth dose escalation plan was obtained allowing comparison between the 20 plans of oropharyngeal cancer patients. RESULTS: It was feasible to escalate dose to the FDG-PET avid tumor within the set constraints to that of planning target volume and OAR. Comparison of the escalated dose to that of standard plans showed a statistically significant (P < 0.05) sparing of the mastication apparatus (MA) with escalated plans. Dose to the other critical and functional organs were comparable between the four plans. CONCLUSION: Hypofractionated, slightly accelerated dose escalation in oropharyngeal cancers is likely to be safe and the chance of trismus is not any higher than when standard dose radiotherapy is used. Active measures to reduce dose to the MA achieves acceptable dose volume parameters even at escalated doses. PMID- 26148607 TI - Association between BIM deletion polymorphism and clinical outcome of EGFR mutated NSCLC patient with EGFR-TKI therapy: A meta-analysis. AB - AIM: BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. MATERIALS AND METHODS: A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. RESULTS: Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (P(h) = 0.309, P(z) = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (P(h) = 0.583, P(Z) = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; P(h) < 0.001, P(z) < 0.001, hazard ratio (HR) = 1.37, 95%CI = 1.09-1.71) and overall survival (OS; P(h) = 0.90, P(z) = 0.003, HR = 1.25, 95%CI = 1.08-1.45), than those harbored BIM wild variant. CONCLUSION: These results suggested that BIM deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient. PMID- 26148608 TI - The effect of mesenchymal stem cells on the p53 methylation in irradiation induced thymoma in C57BL/6 mice. AB - CONTEXT: Our previous studies showed that mesenchymal stem cells (MSCs) preferentially migrated to irradiation-damaged thymus tissue to maintain the thymus integrity and simultaneously decrease the incidence of thymoma from 57 to 37.5%. OBJECTIVE: This study was designed to investigate the mechanisms by which MSCs decrease the irradiation-induced thymoma formation. MATERIALS AND METHODS: Thymus genome DNA was extracted, treated with sulfite, and amplified by polymerase chain reaction (PCR) using bisulfite sequencing PCR (BSP) as primers. The PCR productions were sequenced after recovery from 1.5% agarose gel electrophoresis. These sequences were analyzed using ClustalW2-Multiple Sequence Alignment. p53 expression in thymus or thymoma was measured using immunohistochemistry. RESULTS: Study showed the p53 methylation in irradiation alone group took place at loci +143 and -1190, which are beyond known binding motif of transcription factors. However, Matlnspector Professional Database revealed that locus -1190 is located in binding region of E2A transcription factor. In the non tumor thymus tissues from MSCs-treated irradiated mice, p53 promoter methylation existed at four loci. Three loci of them located at either negative regulation regions or their vicinity. The methylation affects the interaction between transcription factors and p53 promoter to increase the expression of p53. Indeed, an increased p53 expression was detected by immunohistochemistry in thymus tissues from MSCs-treated irradiated mice as compared to irradiated alone mice. CONCLUSION: MSCs decrease the incidence of irradiation-induced thymoma, which may be mediated by improving thymus microenvironment and changing the methylation of p53 promoter, and subsequently maintaining genome's stability. PMID- 26148609 TI - TP 53 polymorphisms and melanoma: A meta-analysis. AB - BACKGROUND: p53 is a tumor suppressor encoded by the TP53 gene. It is critical in activating deoxyribonucleic acid (DNA) repair upon damage, and thus preserving genomic stability. TP53 is implicated in tumor progression. Melanoma results from transformed melanocytes in the skin. Data gathered on the association between the TP53 Arg72, Pro72 (rs1042522; G>C) polymorphism and melanoma are conflicting. AIMS: To assess the relationship between the TP53 genotype and the risk of melanoma, we performed a meta-analysis. MATERIALS AND METHODS: We searched on PubMed for studies of TP53 polymorphism published in English up to 12 th April 2014. For each study, we calculated odds ratio (OR) and 95% confidence interval (CI), assuming frequency of allele comparison, heterozygote comparison, homozygote comparison, dominant, and recessive genetic models. Seven case-control studies were carried out during the meta-analysis. RESULTS: The TP53 Callele was not associated with the risk of melanoma in the frequency of allele comparison (C vs G: OR = 1.031; 95% CI = 0.824-1.290; P < 0.001 for heterogeneity). The TP53 GC genotype was not associated with the risk of melanoma as compared with the GG genotype (GC vs GG: OR = 0.922; 95% CI = 0.716-1.186; P = 0.010 for heterogeneity). The TP53 CC genotype was not associated with the risk of melanoma as revealed by both the homozygote comparison and the recessive genetic model. Analysis of the dominant model also did not indicate a significant association between the TP53 polymorphism and melanoma. CONCLUSIONS: This meta-analysis suggests that genotypes for the TP53 rs1042522 G>C polymorphism might not be associated with the risk of melanoma. PMID- 26148610 TI - Brain cancer surgery in the language areas of Mandarin-Cantonese bilinguals. AB - OBJECTIVE: This study aimed to study methods for protecting the language areas during tumor surgery in Mandarin-Cantonese bilinguals (MCBs). MATERIALS AND METHODS: Eleven MCB patients were positioned for awake surgery with the purpose of preserving both of their language proficiencies. All the exposed cortices were electrically stimulated 1 cm x 1 cm with anelectrode, and all the positive sites of stimulation were recorded for analyses, the tumor resection point was limited by 1cm distant from the language areas identified by electrical stimulation. RESULTS: All patients had at least one language area identified; a total of 154 points were stimulated, with 22 positive points (14.3%), including five specific language areas, which all resulted in simple anomiain either language when stimulated. Among these, three were specific to Mandarin (1.9%), whereas two were specific to Cantonese (1.3%). CONCLUSIONS: In proficient MBCs, areas specific to each language exist. Thus, performing intraoperative bilingual tasks to locate these language areas is necessary in order to preserve language function. PMID- 26148611 TI - RNA-sequencing based identification of crucial genes for esophageal squamous cell carcinoma. AB - AIMS: To identify key genes and pathways in the development of esophageal squamous cell carcinoma with RNA-seq data. MATERIALS AND METHODS: RNA-seq data including three paired samples were downloaded from Sequence Read Archive database under accession number SRP007169 and differentially expressed genes (DEGs) were identified with package edge R of R. Functional enrichment analysis was performed to uncover their biological functions with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tools. RESULTS: A total of 5561 DEGs were obtained, including 1829 upregulated and 3732 downregulated. Quite a few upregulated genes were components of collagen and matrix metallopeptidases (MMPs), which are involved in cell adhesion, cell mobility and so on. Keratin, mucin and cysteine-rich secretory protein were found to be significantly downregulated. Significantly over-represented biological processes for downregulated genes were epidermis development, epidermal cell differentiation and arachidonic acid metabolism. CONCLUSION: These identified DEGs may be underlying targets for diagnosis and treatment of esophageal squamous cell carcinoma. PMID- 26148612 TI - Effect of taurine on attenuating chemotherapy-induced adverse effects in acute lymphoblastic leukemia. AB - OBJECTIVE: The purpose of our study was to evaluate the effect of oral taurine supplementation on the incidence of chemotherapy-induced adverse drug reactions during chemotherapy in young adults with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Forty young adult (aged over 16 years) with ALL, at the beginning of maintenance course of their chemotherapy, were recruited to the study. The study population was randomized in a double blind manner to receive either taurine or placebo. Life quality and adverse drug reactions were assessed using questionnaire. Blood cell count, hemoglobin (Hb), hematocrit (Hct), serum bilirubin, transaminases, urea, and creatinine concentrations were evaluated. Data was analyzed using Statistical Package for Social Sciences (SPSS) software. RESULTS: Of total participants, 43.8% were female and 56.3% were male. The mean age was 19.16 +/- 1.95 years (range: 16-23 years). The results indicated that the levels of white blood cells were significantly (P < 0.05) increased in taurine treated group, but other hematological values did not differ significantly in either group. Taurine administration improved liver and kidney functions, indicated by decline of serum bilirubin, transaminases, urea, and creatinine, respectively in comparison to the controls (P < 0.05). Moreover, taurine significantly reduced serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels (P < 0.05). CONCLUSION: In conclusion our results indicated that taurine supplementation could be a protection against chemotherapy-induced toxicities probably by its antioxidant capacity. Present study showed effectiveness of taurineon the chemotherapy-related toxicities and some of the complications during the maintenance period of treatment following coadministration in young adults with ALL. PMID- 26148613 TI - Adjuvant chemoradiotherapy in periampullary cancers--Where does it stand with conformal radiotherapy: A single institution experience. AB - BACKGROUND: Treatment of periampullary cancer involves Whipple surgery, followed by adjuvant radiotherapy and chemotherapy. Postoperative radiotherapy is particularly useful in managing high-risk patients (tumors involving the pancreas, poorly differentiated histology, involved lymph nodes and positive margins). Here, we review our results of treatment of 84 patients treated by surgery and adjuvant radiotherapy and chemotherapy. MATERIAL AND METHODS: A retrospective analysis of 84 patients of periampullary cancers treated in our department between January 2007 and December 2012 was carried out. All patients underwent Whipples surgery followed by postoperative radiotherapy 45-50 Gy/25-28 number in those presenting with high-risk features. Radiotherapy was delivered using three-dimensional conformal technique with 6 MV photons using three field treatment plans. Chemotherapy was given for 6 cycles using gemcitabine and oxaliplatin regimen repeated 2 weekly. RESULTS: Eighty four postoperative patients with high-risk features were available for the final analysis. There were 69 males and 15 female patients. There were 34.5% stage I, 57.1% stage II and 8.3% stage III patients. At end of adjuvant treatment with radiotherapy and chemotherapy 70% patients had a complete response, 7.5% had residual disease, 15% showed progressive disease, 5% were dead and 2.5% defaulted the treatment. The mean number of chemotherapy cycles received was 2.6. At 1 year follow-up the probability of disease free survival was 80% for node-negative patients versus 73% for node-positive disease (P = 0.27). Patients with stage up to IIA had a 1 year disease free survival of 83% versus 40% for patients with stage beyond IIA (P = 0.024). CONCLUSIONS: Our results showed a trend favoring lymph node negative status with disease free survival. With computed tomography based planning, adequate delineation of draining nodes is possible, and radiation toxicity has significantly decreased. Adequate coverage of nodal basins during radiotherapy planning is important, and stage of the disease seems to be an important prognostic factor. PMID- 26148614 TI - Abnormal cerebral functional connectivity in esophageal cancer patients with theory of mind deficits in resting state. AB - OBJECTIVE: To explore the function of the default mode network (DMN) in the psychopathological mechanisms of theory of mind deficits in patients with an esophageal cancer concomitant with depression in resting the state. SUBJECTS AND METHODS: Twenty-five cases of esophageal cancer with theory of mind deficits (test group) that meet the diagnostic criteria of esophageal cancer and neuropsychological tests, including Beck depression inventory, reading the mind in the eyes, and Faux pas, were included, Another 25 cases of esophageal cancer patients but without theory of mind deficits (control group) were enrolled. Each patient completed a resting-state functional magnetic resonance imaging. RESULTS: The functional connectivity intensities within the cerebral regions in the DMN of all the enrolled patients were analyzed. The results of each group were compared. The functional connectivity of the bilateral prefrontal central region with the precuneus, bilateral posterior cingulate gyrus and bilateral ventral anterior cingulate gyrus in the patients of the test group were all reduced significantly (P < 0.05). In the resting state, the functional connectivity is abnormal in the cerebral regions in the DMN of esophageal cancer patients with theory of mind deficits. CONCLUSIONS: The theory of mind deficits might have an important function in the pathogenesis of esophageal cancer. PMID- 26148615 TI - Endoplasmic reticulum aminopeptidase 2 is highly expressed in papillary thyroid microcarcinoma with cervical lymph node metastasis. AB - BACKGROUND: The cervical lymph node metastasis (CLNM) of papillary thyroid microcarcinoma (PTMC) is not uncommon. However, prophylactic cervical lymph node dissection in all PTMC is debatable. Molecular markers of predicting CLNM would help to decide to either do or not do cervical lymph node dissection which might increase morbidities. AIMS: We aimed to characterize gene expression profiles and molecular markers of CLNM in PTMC. SETTINGS AND DESIGN: The thyroid frozen tissues were obtained with from six PTMC patients, who underwent total thyroidectomy. METHODS: We performed oligonucleotide microarray analysis with three PTMCs with CLNM and three without CLNM. Real-time quantitative reverse transcription-polymerase chain reaction was used to validate the gene. STATISTICAL ANALYSIS USED: We used linear models for microarray data. RESULTS: We identified 12 differentially expressed gene, and most one is endoplasmic reticulum aminopeptidase 2 (ERAP2). CONCLUSION: ERAP2 might be associated with CLNM in PTMC. PMID- 26148616 TI - Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods. AB - PURPOSE: The aim of this study was to compare the radioprotective efficacies of L carnitine (LC) and amifostine against radiation-induced acute ovarian damage. MATERIALS AND METHODS: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7); irradiation alone RT: radiation therapy (RT, n = 8); amifostine plus irradiation (AMI + RT, n = 8); LC plus irradiation (LC + RT, n = 8); LC and sham irradiation (LC, n = 7); and amifostine and sham irradiation (AMI, n = 7). The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg) and amifostine (200 mg/kg) was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA) and advanced oxidation protein product (AOPP) were measured. RESULTS: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P < 0.0001). LC increased the median number of antral follicles and corpus luteum (P: 0.009 and P < 0.0001, respectively). Amifostine improved median corpus luteum numbers but not antral follicle (P < 0.000, P > 0.05). The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P < 0.0001, respectively). MDA and AOPP levels were significantly reduced by LC (P: 0.003, P < 0.0001) and amifostine (P < 0.0001, P: 0.018). When comparing CONT group with AMI + RT and LC + RT groups, MDA and AOPP levels were similar (P > 0.005). The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005). CONCLUSIONS: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity. PMID- 26148617 TI - Ligustrazine induces apoptosis of breast cancer cells in vitro and in vivo. AB - INTRODUCTION: Ligustrazine, the active ingredient present in Umbelliferae plant roots used in Chinese medicine, plays a vital role in reversing multidrug resistance in tumors. This study aims to investigate its anticancer activity and underlying mechanisms in human breast cancer cells in vitro and in vivo. MATERIALS AND METHODS: Human breast cancer cell line MDA-MB-231 was incubated with different concentrations of ligustrazine. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; and cell apoptosis and cell cycle were assessed by flow cytometry. Subcutaneous MDA MB-231 xenograft tumors were established in nude BALB/c mice. Ligustrazine was intraperitoneally administered. The tumor growth was monitored. RESULTS: In vitro, ligustrazine inhibited cell survival in a dose-and time-dependent manner, and induced apoptosis, as indicated by a dramatic increase in sub-G0/G1 cells. The in vivo results were consistent with the in vitro ones: Administration of ligustrazine substantially inhibited tumor growth, which also indicated that ligustrazine inhibited proliferation of MDA-MB-231 cells in vitro. CONCLUSIONS: Ligustrazine causes apoptotic death and tumor regression in human breast cancer cells in vitro and in vivo models. PMID- 26148618 TI - Differences of polyunsaturated fatty acid in patients with colorectal cancer and healthy people. AB - OBJECTIVE: This study aims to compare the difference of polyunsaturated fatty acid (PUFA) between patients with colorectal cancer and healthy people and analyze the effect of PUFA on colorectal cancer by testing serum of PUFA. MATERIALS AND METHODS: One hundred and fifty-six healthy people and 79 patients with colorectal cancer were randomly chosen in Beijing, China. PUFA level was measured in two groups. According to different stages, sizes, degree of differentiation, lymph node metastases from patients with colorectal cancer, we compared metabolize situation of PUFA. RESULTS: Total omega-6 PUFA level was higher in healthy people group than that in colorectal cancer group (25.77 +/- 3.21 vs. 26.86 +/- 1.65, P = 0.0125); moreover, arachidonic acid (AA) level was also higher in healthy people group than that in colorectal cancer group (5.02 +/ 1.32 vs. 6.08 +/- 1.26, P = 0.0344); total omega-3 PUFA level was lower in colorectal cancer group than that in healthy people group; furthermore, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was also lower in colorectal cancer group than that in healthy people group. AA and total omega-6 were significant differences between less than 5 cm of tumor size and more than 5 cm of tumor size (13.11 +/- 2.91 vs. 14.44 +/- 1.81, P < 0.05; 27.02 +/- 4.54 vs. 28.76 +/- 3.08, P < 0.05). CONCLUSION: PUFA level was significant difference between healthy people and colorectal cancer patients in the Chinese population. Tumor size probably had influence on the metabolism of PUFA. PMID- 26148619 TI - Treatment of oral leukoplakia with photodynamic therapy: A pilot study. AB - AIM OF THE STUDY: Oral leukoplakia (OL) is the most common potentially malignant disorder that may transform into oral carcinoma. By treating leukoplakia in its incipient stage, the risk of occurrence of oral carcinoma can be prevented. In this aspect, photodynamic therapy (PDT) can serve as a useful treatment modality. The aim of the study is to treat patients with OL using PDT in which 5 aminolevulinic acid (ALA) is used as a photosensitizer. MATERIALS AND METHODS: Five patients with OL were included in the study. They were treated with 10% ALA mediated PDT (light source: Xenon lamp, power: 0.1 W, wavelength: 630 +/- 5 nm, total dose: 100 J/cm(2) per session) for 6-8 sessions. Follow-up was done for a period of 1 year. RESULTS: One month (4 weeks) after ALA-PDT, the response was evaluated based on clinical examination. It was as follows: Complete response: Two patients; partial response: Two patients; and no response: One patient. There was no recurrence in any of the cases. CONCLUSION: There was satisfactory reduction in the size of the OL lesion without any side-effects. Thus, ALA mediated PDT seems to be a promising alternative for the treatment of OL. PMID- 26148620 TI - Genetic variants identified by GWAS was associated with colorectal cancer in the Han Chinese population. AB - AIM OF STUDY: Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. Recently, genome-wide association studies have identified two single nucleotide polymorphisms (SNP) associated with CRC in Caucasians. MATERIALS AND METHODS: To validate whether the same variations conferred risk to CRC in the Han Chinese population, we genotyped 760 individuals (380 controls and 380 cases samples) recruited from the Han Chinese origin. RESULTS: We found rs11987193 in 8p12 (P = 0.0472 after correction, OR = 0.751) was significantly associated with CRC but rs12080929 in 1p33 (P = 0.0650 after correction, OR = 0.750) was not. CONCLUSION: Our findings supported that rs11987193 is a susceptibility locus for CRC, and gene DUSP4 was possible to play a role in the pathology of CRC. PMID- 26148621 TI - Role of oral exfoliative cytology in predicting premalignant potential of oral submucous fibrosis: A short study. AB - The present study was undertaken with an aim of determining the cytological features observed in mucosal smears of oral submucous fibrosis (OSF) patients and comparing them with that of features of normal mucosal cells. The observed features were than analyzed for their reliability in detecting malignant changes in this premalignant condition. Objective of the study was to conduct an oral exfoliative cytology (OEC) study on 30 clinically diagnosed cases of OSF and 30 cases of clinically normal mucosa with no other systemic disease. We observed that all the smears from clinically normal buccal mucosa showed Class I cytology. The exfoliated cells were of normal size and shape with normal staining intensity and normal nuclear characteristics. All the 30 cases of our study group showed features suggestive of benign atypical cytological changes (Class II cytology). In the present study, despite the small number of cases, cytological features consistently observed in all the cases, were indicative of a premalignant change and emphasized a regular follow-up of patients. Early detection of a premalignant oral lesion promises to improve the survival rate of patients suffering from these conditions. PMID- 26148622 TI - Combination of retrograde superselective intra-arterial chemotherapy and Seldinger method in locally advanced oral cancer. AB - The nonsurgical strategies for locally advanced oral cancer are desirable. Superselective intra-arterial infusion with radiotherapy was utilized for this purpose, and there are two types of superselective intra-arterial infusion methods: The Seldinger method and the retrograde superselective intra-arterial chemotherapy (HFT method). In one case, the HFT method was applied to locally advanced tongue cancer, and the Seldinger method was used for additional administration of cisplatin (CDDP) to compensate for a lack of drug flow in the HFT method. In another case, the HFT method was applied to locally advanced lower gingival cancer. The Seldinger method was applied to metastatic lymph nodes. In both cases, additional administration of CDDP using the Seldinger method resulted in a complete response. The combination of the HFT and Seldinger methods was useful to eradicate locally advanced oral cancer because each method compensated for the defects of the other. PMID- 26148623 TI - Living with the Elekta Compact: Limitations and ways around them. AB - Elekta AB, Sweden has recently propagated the Elekta Compact--a low-cost, small footprint, single energy (6MV), linear accelerator, in India. The absence of electron beams and the inability to seamlessly deliver inverse planned intensity modulated radiotherapy (IMRT) segments, mean that some out-of-the-box thinking is mandatory for the full range of required treatments in different clinical settings, but is ultimately very rewarding. Our department started off in July 2011, with the Elekta Compact, equipped with MLCi2 and a camera-based electron portal imaging device. For head-neck cancers, we have successfully utilized a 3D conformal class-solution of eight-to-nine oblique beams, with multiple segments, to deliver an adequate dose to the posterior neck, respecting spinal cord tolerance. Parotid gland sparing is possible in selected node-negative hypopharyngeal/laryngeal cancers. For prostate cancers, we have developed a forward-planned IMRT protocol to routinely deliver 76-80 Gy to the prostate, with margins, while conforming to the same rectal dose-volume constraints as in inverse IMRT. Response and tolerance have been excellent so far. In head-neck cancers, the majority (71%) of patients was locally advanced; however, complete response was achieved in 75% of the cases. Grade 3 acute toxicities were seen in only 7% of the cases and compliance overall was excellent, with no patients requiring a gap in treatment. We achieved biochemical control in 100% of the prostate cancer patients; no patients had grade 3 acute toxicities, and with a median follow-up of 12 months, have yet to see any late rectal bleeding. Although engineered for simplicity and versatility, the Compact requires some innovative thinking by clinicians/physicists to optimize the full range of its possibilities. However, upgrades like inverse IMRT delivery, which are in the pipeline, are urgently needed for it to be viable, especially in a single accelerator department. PMID- 26148624 TI - Issues of sample size in sensitivity and specificity analysis with special reference to oncology. AB - Sample size is one of the basics issues, which medical researcher including oncologist faces with any research program. The current communication attempts to discuss the computation of sample size when sensitivity and specificity are being evaluated. The article intends to present the situation that the researcher could easily visualize for appropriate use of sample size techniques for sensitivity and specificity when any screening method for early detection of cancer is in question. Moreover, the researcher would be in a position to efficiently communicate with a statistician for sample size computation and most importantly applicability of the results under the conditions of the negotiated precision. PMID- 26148625 TI - Bevacizumab alleviates radiation-induced brain necrosis: A report of four cases. AB - To analyze the therapeutic effect of bevacizumab on radiation-induced brain necrosis. Four radiation-induced brain necrosis patients, administered with bevacizumab at a dose of 7.5 mg/kg every 3 weeks, 2 times. One case of brain metastasis of lung cancer and one case of nasopharyngeal carcinoma with brain necrosis after radiotherapy. However, their physical signs disappeared after the treatment with bevacizumab. One case of brainstem lesion and one case of brain glioma patient showed a transient improvement in signs and symptoms after treatment with bevacizumab. Bevacizumab can significantly alleviate the radiation induced brain edema, and can improve the symptoms successively. PMID- 26148626 TI - A technique to reduce low dose region for craniospinal irradiation (CSI) with RapidArc and its dosimetric comparison with 3D conformal technique (3DCRT). AB - We proposed a method to reduce the volume of normal tissues irradiated by low doses in patients receiving CSI with RapidArc (RA) using Avoidance-Sector technique (RA+AS) and to compare its dosimetric implications with RA using full arc (RA+FA) and 3D conformal technique (3DCRT). Four patients of CSI were retrospectively planned with 3DCRT, RA+FA, and RA+AS. Conformity-Index (CI), Homogeneity-Index (HI), and Paddick Gradient-Index (GI) were calculated. Quantitative evaluation was done using DVH analysis for PTVs and OARs. When compared with 3DCRT, GI, CI, and HI were favorable to RA based techniques. In comparison with 3DCRT the doses to OARs were lower with RA+AS with the difference being statistically significant in most instances. RA+AS significantly decreases the dose to OARs and their volumes receiving low doses in comparison with RA+FA and 3DCRT. PMID- 26148627 TI - Basaloid squamous cell carcinoma of cervix showing neuroendocrine differentiation. PMID- 26148628 TI - Fibrolamellar hepatocellular carcinoma with extensive vascular thrombosis. PMID- 26148629 TI - Role of polyhydroxyalkanoates in cancer and other drug delivery systems. PMID- 26148630 TI - Carotid sparing intensity-modulated radiotherapy in early glottic cancers: A case of Maslow's hammer? PMID- 26148631 TI - A rare case of melanotic malignant trichoblastoma. PMID- 26148632 TI - Acute myeloid leukemia in a child with segmental neurofibromatosis. PMID- 26148634 TI - ? PMID- 26148633 TI - A paradigm shift in the treatment of atherosclerosis. PMID- 26148635 TI - The multifaceted KDAC8: a smooth muscle contractile regulator. PMID- 26148636 TI - Novel therapeutics in myocardial infarction: targeting microvascular dysfunction and reperfusion injury. AB - Despite the large number of novel therapies under basic scientific investigation, the translation of cardioprotective strategies targeting reperfusion injury to improve patient outcomes following percutaneous coronary intervention (PCI) for myocardial infarction (MI) has been disappointing. The varying susceptibility of an individual to reperfusion injury, as well as the narrow window of opportunity in which to intervene, adds significant complexity. Here, we discuss the unmet need and challenges of translating cardioprotective strategies into clinical practice, review the pathophysiology of microvascular dysfunction and lethal reperfusion as they relate to promising novel therapeutics, and evaluate recent and ongoing clinical trials in the field. PMID- 26148637 TI - Retinal structural features of cytomegalovirus retinitis with acquired immunodeficiency syndrome: an adaptive optics imaging and optical coherence tomography study. PMID- 26148638 TI - Improved dynamic parallel imaging coil calibration method robust to respiratory motion with application to first-pass contrast-enhanced myocardial perfusion imaging. AB - PURPOSE: To develop an accurate method of performing free-breathing coil calibration for application to parallel imaging reconstructions of dynamic single shot datasets. METHODS: Coil calibration data are produced through acquisition of multiple prescans before the accelerated scan, applied during free-breathing. These multiple free-breathing prescans (MFPs) provide the necessary coil information for accurate parallel imaging reconstruction of each accelerated frame of a dynamic series, under guidance of an appropriate respiratory position based matching algorithm. This is investigated in myocardial first-pass perfusion with retrospectively undersampled datasets for analysis with standard calibration techniques to guide prospectively undersampled experiments for specific demonstration of performance against a range of "temporal" calibration techniques. RESULTS: Reconstruction of the retrospectively subsampled datasets with MFP-calibrated parallel imaging showed significant improvements in relative root-mean-square error comparative to all other techniques (all P < 0.05; n = 6) for acceleration factors R > 3. Accelerated acquisitions, reconstructed by means of various temporal calibration techniques and analyzed by visual observer artifact scoring, also demonstrated a large improvement with use of MFPs. Artifact levels were reduced from an average of 2.5 +/- 0.6 for the best performing implementation of TGRAPPA to 0.8 +/- 0.4 for MFP-GRAPPA (P < 0.001; n = 20) (0 = none to 4 = strong, nondiagnostic). CONCLUSION: MFP as parallel imaging coil calibration data can give improved performance in free-breathing dynamic MR while maintaining maximal acceleration. Magn Reson Med 75:2315-2323, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26148639 TI - 35 years of the Nordic College of Caring Science - heading for the future. PMID- 26148640 TI - The Role of Common Femoral Artery Endarterectomy in the Endovascular Era. AB - BACKGROUND: The purpose of this study was to review our experiences treating peripheral artery disease (PAD) by common femoral artery endarterectomy (CFE) with and without endovascular therapy (EVT), and to describe the role of CFE in the endovascular era. METHODS: We retrospectively reviewed a contemporary series of 38 limbs from January 2010 to September 2014. Clinical outcomes of primary patency, assisted primary patency, limb salvage, and survival were analyzed with the Kaplan-Meier method. Multivariable perioperative predictors of primary patency were identified using the stepwise Cox proportional hazards regression model. RESULTS: Hemodynamic success was achieved in 36 of the 38 limbs (95%). The mean ankle brachial pressure index improved significantly, rising from 0.56 +/- 0.04 preoperatively to 0.89 +/- 0.04 postoperatively (P = 0.0001). Overall primary and assisted primary patency rates, respectively, were 90% and 100% at 12 months and 85% and 94% at 24 months. There was no significant difference in primary patency rate between isolated CFE and hybrid CFE plus EVT. Both limb salvage and survival rates were 97% at 12 months and 97% at 24 months. Multivariate Cox regression analysis revealed that no clinical or perioperative risk factors were predictive of decreased primary patency. CONCLUSIONS: CFE is a safe, effective, and durable procedure for common femoral artery disease, and hybrid CFE plus EVT can be a valid alternative to open surgical bypass for multilevel occlusive artery disease. These observations stress that CFE plays a vital role in the management of PAD even in the endovascular era. PMID- 26148642 TI - Enrichment of heavy metals in fine particles of municipal solid waste incinerator (MSWI) fly ash and associated health risk. AB - During the pretreatment and recycling processes, the re-suspended dust from municipal solid waste incinerator (MSWI) fly ash might pose a significant health risk to onsite workers due to its toxic heavy metal content. In this work, the morphological and mineralogical characteristics of fly ash in different particle sizes are presented. The concentrations of seven trace elements (Zn, Pb, Cu, Cd, Cr, Fe and Mn) in these samples were determined. The results show that volatile metals, such as Zn, Pb, Cu and Cd, were easily concentrated in the fine particles, especially in Dp2.5-1 and Dp1, with soluble and exchangeable substances as the main chemical species. The health risk assessment illustrated that the cumulative hazard indexes for non-carcinogenic metals in Dp10-5, Dp5 2.5, Dp2.5-1, and Dp1 were 1.69, 1.41, 1.78 and 2.64, respectively, which were higher than the acceptable threshold values (1.0). The cumulative carcinogenic risk was also higher than the threshold value (10(-6)). For the onsite workers, the relatively apparent non-carcinogenic and carcinogenic effects were from Pb and Cr, respectively. The above findings suggest that fine-grained fly ash contained a considerable amount of heavy metals and exhibited a great health risk. PMID- 26148643 TI - Quantifying capture efficiency of gas collection wells with gas tracers. AB - A new in situ method for directly measuring the gas collection efficiency in the region around a gas extraction well was developed. Thirteen tests were conducted by injecting a small volume of gas tracer sequentially at different locations in the landfill cell, and the gas tracer mass collected from each test was used to assess the collection efficiency at each injection point. For 11 tests the gas collection was excellent, always exceeding 70% with seven tests showing a collection efficiency exceeding 90%. For one test the gas collection efficiency was 8+/-6%. Here, the poor efficiency was associated with a water-laden refuse or remnant daily cover soil located between the point of tracer injection and the extraction well. The utility of in situ gas tracer tests for quantifying landfill gas capture at particular locations within a landfill cell was demonstrated. While there are certainly limitations to this technology, this method may be a valuable tool to help answer questions related to landfill gas collection efficiency and gas flow within landfills. Quantitative data from tracer tests may help assess the utility and cost-effectiveness of alternative cover systems, well designs and landfill gas collection management practices. PMID- 26148644 TI - Assessment of biogas production from MBT waste under different operating conditions. AB - In this work, the influence of different operating conditions on the biogas production from mechanically-biologically treated (MBT) wastes is investigated. Specifically, different lab-scale anaerobic tests varying the water content (26 43% w/w up to 75% w/w), the temperature (from 20 to 25 degrees C up to 55 degrees C) and the amount of inoculum have been performed on waste samples collected from a full-scale Italian MBT plant. For each test, the gas generation yield and, where applicable, the first-order gas generation rates were determined. Nearly all tests were characterised by a quite long lag-phase. This result was mainly ascribed to the inhibition effects resulting from the high concentrations of volatile fatty acids (VFAs) and ammonia detected in the different stages of the experiments. Furthermore, water content was found as one of the key factor limiting the anaerobic biological process. Indeed, the experimental results showed that when the moisture was lower than 32% w/w, the methanogenic microbial activity was completely inhibited. For the higher water content tested (75% w/w), high values of accumulated gas volume (up to 150Nl/kgTS) and a relatively short time period to deplete the MBT waste gas generation capacity were observed. At these test conditions, the effect of temperature became evident, leading to gas generation rates of 0.007d(-1) at room temperature that increased to 0.03-0.05d( 1) at 37 degrees C and to 0.04-0.11d(-1) at 55 degrees C. Overall, the obtained results highlighted that the operative conditions can drastically affect the gas production from MBT wastes. This suggests that particular caution should be paid when using the results of lab-scale tests for the evaluation of long-term behaviour expected in the field where the boundary conditions change continuously and vary significantly depending on the climate, the landfill operative management strategies in place (e.g. leachate recirculation, waste disposal methods), the hydraulic characteristics of disposed waste, the presence and type of temporary and final cover systems. PMID- 26148645 TI - Oxidation and waste-to-energy output of aluminium waste packaging during incineration: A laboratory study. AB - This work reports the oxidation behaviour and waste-to-energy output of different semi-rigid and flexible aluminium packagings when incinerated at 850 degrees C in an air atmosphere enriched with 6% oxygen, in the laboratory setting. The physical properties of the different packagings were determined, including their metallic aluminium contents. The ash contents of their combustion products were determined according to standard BS ISO 1171:2010. The net calorific value, the required energy, and the calorific gain associated with each packaging type were determined following standard BS EN 13431:2004. Packagings with an aluminium lamina thickness of >50MUm did not fully oxidise. During incineration, the weight for-weight waste-to-energy output of the packagings with thick aluminium lamina was lower than that of packagings with thin lamina. The calorific gain depended on the degree of oxidation of the metallic aluminium, but was greater than zero for all the packagings studied. Waste aluminium may therefore be said to act as an energy source in municipal solid waste incineration systems. PMID- 26148646 TI - Covalently Binding Atomically Designed Au9 Clusters to Chemically Modified Graphene. AB - Atomic-resolution transmission electron microscopy was used to identify individual Au9 clusters on a sulfur-functionalized graphene surface. The clusters were preformed in solution and covalently attached to the surface without any dispersion or aggregation. Comparison of the experimental images with simulations allowed the rotational motion, without lateral displacement, of individual clusters to be discerned, thereby demonstrating a robust covalent attachment of intact clusters to the graphene surface. PMID- 26148647 TI - Topographical distribution of anopheline mosquitoes in an area under elimination programme in the south of Iran. AB - BACKGROUND: Malaria is a major vector-borne disease in tropical and sub-tropical countries caused by Plasmodium infection. It is one the most important health problem in south and southeast of Iran. Since Iran has recently launched to the elimination phase of malaria and vector control is one of the main strategies for elimination, this study was conducted to determine the topographical distribution of malaria vectors in Minab County, one of the important malaria endemic areas in south of Iran. METHODS: In this cross-sectional study, six villages in three topographically different sites namely coastal plain, foothill and mountainous areas were selected by simple random sampling. The anopheline larvae were collected using the standard dipping method. The specimens were identified using a morphology based-key. Statistical analyses were performed using SPSS ver.16 software. RESULTS: In total, 3,841 anopheles larvae were collected from 24 larval habitats. They consisted of ten species: Anopheles moghulensis (25.23%), Anopheles stephensi (24.47%), Anopheles dthali (19.14%), Anopheles culicifacies (9.63%), Anopheles fluviatilis (7.52%), Anopheles superpictus (5.62%), Anopheles turkhudi (5.55%), Anopheles pulcherrimus (1.93%), Anopheles multicolor (0.47%), and Anopheles apoci (0.44%). Most species were distributed in different topographies and only An. Stephensi and An. culicifacies, the main malaria vectors in Iran, were significantly associated with the altitude of studied areas. An. moghulensis, An. stephensi and An. dthali were the most widespread species and were, respectively predominant in Coastal plain, foothill and mountainous areas. CONCLUSION: Results of this study have revealed that there are many malaria vectors that are distributed in Minab County and some of them are expected to be predominant in areas with special topographic characteristics. This finding can provide a basis for effective planning and implementation of evidence-based malaria vector intervention strategies towards vector control, which may help in malaria elimination in the study area. PMID- 26148648 TI - Pneumothorax Complicating Coaxial and Non-coaxial CT-Guided Lung Biopsy: Comparative Analysis of Determining Risk Factors and Management of Pneumothorax in a Retrospective Review of 650 Patients. AB - PURPOSE: To assess the scope and determining risk factors related to the development of pneumothorax throughout CT-guided biopsy of pulmonary lesions in coaxial and non-coaxial techniques and the outcome of its management. MATERIALS AND METHODS: The study included CT-guided percutaneous lung biopsies in 650 consecutive patients (407 males, 243 females; mean age 54.6 years, SD 5.2) from November 2008 to June 2013 in a retrospective design. Patients were classified according to lung biopsy technique into coaxial group (318 lesions) and non coaxial group (332 lesions). Exclusion criteria for biopsy were lesions <5 mm in diameter, uncorrectable coagulopathy, positive-pressure ventilation, severe respiratory compromise, pulmonary arterial hypertension, or refusal of the procedure. Risk factors related to the occurrence of pneumothorax were classified into: (a) Technical risk factors, (b) patient-related risk factors, and (c) lesion-associated risk factors. Radiological assessments were performed by two radiologists in consensus. Mann-Whitney U test and Fisher's exact tests were used for statistical analysis. p values <0.05 were considered statistically significant. RESULTS: The incidence of pneumothorax complicating CT-guided lung biopsy was less in the non-coaxial group (23.2 %, 77 out of 332) than the coaxial group (27 %, 86 out of 318). However, the difference in incidence between both groups was statistically insignificant (p = 0.14). Significant risk factors for the development of pneumothorax in both groups were emphysema (p < 0.001 in both groups), traversing a fissure with the biopsy needle (p value 0.005 in non coaxial group and 0.001 in coaxial group), small lesion, less than 2 cm in diameter (p value of 0.02 in both groups), location of the lesion in the basal or mid sections of the lung (p = 0.003 and <0.001 in non-coaxial and coaxial groups, respectively), and increased needle track path within the lung tissue of more than 2.5 cm (p = 0.01 in both groups). The incidence of pneumothorax in the non coaxial group was significantly correlated to the number of specimens obtained (p = 0.006). This factor was statistically insignificant in the coaxial group (p = 0.45). The biopsy yield was more diagnostic and conclusive in the coaxial group in comparison to the non-coaxial group (p = 0.008). Simultaneous incidence of pneumothorax and pulmonary hemorrhage was 27.3 % (21/77) in non-coaxial group and in 30.2 % (26/86) in coaxial group. Conservative management was sufficient for treatment of 91 out of 101 patients of pneumothorax in both groups (90.1 %). Manual evacuation of pneumothorax was efficient in 44/51 patients (86.3 %) in both groups and intercostal chest tube was applied after failure of manual evacuation (7 patients: 13.7 %), from which one patient developed a persistent air leakage necessitating pleurodesis. CONCLUSION: Pneumothorax complicating CT guided core biopsy of pulmonary lesions, showed the insignificant difference between coaxial and non-coaxial techniques. However, both techniques have the same significant risk factors including small and basal lesions, increased lesion's depth from pleural surface, and increased length of aerated lung parenchyma crossed by biopsy needle and passing through pulmonary fissures in the needle tract. PMID- 26148649 TI - CT-Guided Percutaneous Radiologic Gastrostomy for Patients with Head and Neck Cancer: A Retrospective Evaluation in 177 Patients. AB - PURPOSE: The purpose of this study was to assess the technical success rate and adverse events (AEs) associated with computed tomography (CT)-guided percutaneous gastrostomy for patients with head and neck cancer (HNC). MATERIALS AND METHODS: This retrospective study included patients with HNC who had undergone CT-guided percutaneous gastrostomy between February 2007 and December 2013. Information regarding the patients' backgrounds, CT-guided percutaneous gastrostomy techniques, technical success rate, and AEs were obtained from the medical records. In all patients, the stomach was punctured under CT fluoroscopy with a Funada gastropexy device. RESULTS: During the study period, 177 patients underwent CT-guided percutaneous gastrostomy. The most common tumor location was the oral cavity, followed by the pharynx and maxilla. The indication for CT guided percutaneous gastrostomy were tumor obstruction in 78 patients, postoperative dysphagia in 55 patients, radiation edema in 43 patients, and cerebral infarction in 1 patient. The technical success rate was 97.7 %. The overall mean procedure time was 25.3 min. Major AEs occurred in seven patients (4.0 %), including bleeding (n = 4), colonic injury (n = 1), gastric tear (n = 1), and aspiration pneumonia (n = 1). Minor AEs occurred in 15 patients (8.5 %), which included peristomal leakage (n = 6), irritation (n = 4), inadvertent removal (n = 2), peristomal hemorrhage (n = 1), peristomal infection (n = 1), and wound granulation (n = 1). The mean follow-up period was 111 days (range 1-1106 days). CONCLUSION: Our study suggests that CT-guided gastrostomy may be suitable in patients with HNC. PMID- 26148650 TI - TB or not TB--Persistent cough, fever and night sweats in a 46-year-old traveler returning from South America. PMID- 26148651 TI - Standards of yellow fever vaccination and travel medicine practice in the Republic of Ireland: A questionnaire-based evaluation. AB - BACKGROUND: The Department of Health regulates the designation of yellow fever vaccination centres (YFVCs) in the Republic of Ireland to ensure appropriate standards in the safe, effective use of yellow fever vaccine for overseas travellers. The process of designation of YFVCs is delegated to Directors of Public Health who direct Principal Medical Officers. Variation in implementation of specific criteria for designation exists and no formal follow up inspection is carried out. This survey of all designated YFVCs in the Republic of Ireland aimed to assess compliance with standards to ensure the objectives of the national yellow fever vaccination programme were met. METHODS: A piloted questionnaire devised from a United Kingdom (UK) YFVC survey was developed and tested in five YFVCs. The questionnaire was adapted for the postal survey and captured data on professional training, reference sources, services provided, physical facilities and supplies, and was distributed to 655 YFVCs in a stamped addressed envelope. RESULTS: During the period 2010-2011, there were 655 designated YFVCs in the Republic of Ireland. Responses were received from 246 centres (38% response rate), 91% of which were in general practice. Deficiencies were identified in respect of vaccine refrigeration protocols, record keeping, attendance at YFVC training sessions, and clinical protocols for adverse events. CONCLUSIONS: Specific deficiencies in relation to training, vaccine storage, administration and documentation should be addressed to ensure standardised YFVC practices and thus align them with best international practice. PMID- 26148652 TI - Transition probability estimates for non-Markov multi-state models. AB - Non-parametric estimation of the transition probabilities in multi-state models is considered for non-Markov processes. Firstly, a generalization of the estimator of Pepe et al., (1991) (Statistics in Medicine) is given for a class of progressive multi-state models based on the difference between Kaplan-Meier estimators. Secondly, a general estimator for progressive or non-progressive models is proposed based upon constructed univariate survival or competing risks processes which retain the Markov property. The properties of the estimators and their associated standard errors are investigated through simulation. The estimators are demonstrated on datasets relating to survival and recurrence in patients with colon cancer and prothrombin levels in liver cirrhosis patients. PMID- 26148653 TI - Chronic stress of rainbow trout Oncorhynchus mykiss at high altitude: a field study. AB - The stress response of Oncorhynchus mykiss in high-altitude farms in central Mexico was investigated over two seasons: the cool (9.1-13.7 degrees C) dry winter season, and the warmer (14.7-15.9 degrees C), wetter summer season. Fish were subjected to an acute stress test followed by sampling of six physiological variables: blood cortisol, glucose, lactate, total antioxidant capacity, haemoglobin concentration and per cent packed cell volume (VPC %). Multivariate analyses revealed that lactate and total antioxidant capacity were significantly higher in the summer, when water temperatures were warmer and moderate hypoxia (4.9-5.3 mg l(-1) ) prevailed. In contrast, plasma cortisol was significantly higher in the winter (mean +/- s.e.: 76.7 +/- 4.0 ng ml(-1) ) when temperatures were cooler and dissolved oxygen levels higher (6.05-7.9 mg l(-1) ), than in the summer (22.7 +/- 3.8 ng ml(-1) ). Haemoglobin concentrations (mg dl(-1) ) were not significantly different between seasons, but VPC % was significantly higher in the summer (50%) than in the winter (35%). These results suggest that in summer, effects of high altitude on farmed fish are exacerbated by stresses of high temperatures and hypoxia, resulting in higher blood lactate, increased total antioxidant capacity and elevated VPC % levels. PMID- 26148654 TI - Effects of extra irradiation on surface and bulk properties of PMPC-grafted cross linked polyethylene. AB - Sterilization using high-energy irradiation is an important aspect of implementing an ultra-high molecular weight polyethylene acetabular liner in total hip arthroplasty (THA). In this study, we evaluate the effects of extra irradiations such as gamma-ray or plasma irradiation during sterilization of the poly(2-methacryloyloxyethyl phosphorylcholine [MPC]) (PMPC) surface and cross linked polyethylene (CLPE) substrate of a PMPC-grafted CLPE acetabular liner. The PMPC-grafted surface yielded high wettability and low friction properties regardless of the extra irradiations as compared with untreated CLPE. During a hip simulator test, wear resistance of the PMPC-grafted CLPE liner was maintained after extra irradiation, which is due to the high wettability characteristics of the PMPC surface. In particular, the PMPC-grafted CLPE liner treated with plasma irradiation showed greater wettability and wear resistance than that with gamma ray irradiation. However, we could not clearly observe the changes in chemical properties and morphology of the PMPC surface after both extra irradiations. The physical and mechanical properties attributed to CLPE substrate performance were also unchanged. In contrast, PMPC-grafted CLPE treated with plasma irradiation showed improved oxidation resistance as compared to that treated with gamma-ray irradiation after accelerated aging. Thus, we conclude that PMPC-grafted CLPE with plasma irradiation has promise as a lifelong solution for bearing in THA. PMID- 26148655 TI - Oxygen isotope ratios in primate bone carbonate reflect amount of leaves and vertical stratification in the diet. AB - The stable isotopic biogeochemistry of free-ranging primates is a unique tool to assess dietary and ecological adaptions among sympatric populations. The present study tested the hypothesis that oxygen isotopes in the bone carbonate of five primate and four ungulate species that live in Kibale National Park, Uganda, would show minimal variability since the species obtain water from a single water source. Bones were analyzed for stable carbon (delta(13) C) and oxygen (delta(18) O) isotope ratios. Results for apatite delta(13) C are consistent with all species feeding in a closed forest habitat and do not exhibit niche partitioning. delta(18) O values, in contrast, cluster by species and correlate positively with the relative contribution of leaves to the whole diet are likely also modified by vertical niche partitioning between taxa within the forest canopy. These results show that biochemical markers from naturally deceased primate remains can aid our understanding of how living animals exploit available resources. Am. J. Primatol. 78:1086-1097, 2016 (c) 2015 Wiley Periodicals, Inc. PMID- 26148657 TI - Impact of Surgery for Neonatal Gastrointestinal Diseases on Weight and Fat Mass. AB - OBJECTIVE: To compare growth, fat mass (FM), and fat-free mass in surgical infants vs matched controls at similar postconceptional age (PCA). STUDY DESIGN: Anthropometric and body composition measurements by air-displacement plethysmography (PeaPod-Infant Body Composition System; LMI, Concord, California) were performed at the same PCA in 21 infants who received gastrointestinal surgery and in 21 controls matched for gestational age, birth weight, and sex. RESULTS: Despite similar anthropometry at birth, postsurgical infants were shorter (50.4 [4.7] cm vs 53.2 [4.1] cm, P = .001), lighter (3516 [743] g vs 3946 [874] g, P < .001), and had lower FM content (%FM 14.8 [4.7]% vs 20.2 [5.8]%, P < .0001) than their peers at similar PCA (43 [4] weeks). All surgical infants but 1 (20/21) received parenteral nutrition (PN). Mean PN duration was 40 (30) days. Five infants in the control group received PN because of prematurity for 15 (9 30) days. Nine infants in the surgical group and 1 in the control group had PN associated cholestasis. CONCLUSIONS: Neonates having surgery for gastrointestinal diseases were shorter, had lower weight, and lower FM content than their peers, despite receiving more PN. Body composition evaluation and monitoring may help optimize growth in these newborns. PMID- 26148658 TI - Unraveling Gene Interactions in Patients with Neurofibromatosis Type 1. PMID- 26148656 TI - Hepatitis viruses exploitation of host DNA methyltransferases functions. AB - Hepatitis B virus (HBV), hepatitis C virus (HCV) and Delta (HDV) infections are a global health burden. With different routes of infection and biology, HBV, HCV and HDV are capable to induce liver cirrhosis and cancer by impinging on epigenetic mechanisms altering host cell's pathways. In the present manuscript, we reviewed the published studies taking into account the relationship between the hepatitis viruses and the DNA methyltransferases proteins. PMID- 26148659 TI - Health Service Use and Costs Associated with Low Birth Weight--A Population Level Analysis. AB - OBJECTIVES: To examine differences in health services utilization (HSU) costs in the first year of life between low birth weight (LBW) and normal birth weight (NBW) infants, identify maternal and child characteristics associated with HSU costs, and estimate annual HSU cost of LBW infants for the province of Alberta, Canada. STUDY DESIGN: A retrospective cohort study including all live births between 2004 and 2010. Data from the Alberta Perinatal Health Program database were linked to health care administrative data including inpatient, outpatient, and practitioner claims to identify HSU within the first year of life. RESULTS: One-year HSU costs among LBW infants (n = 16,209) were $33,096 compared with $3942 among NBW infants (n = 189,586). There was a strong negative correlation between HSU costs and increasing birth weight, with health care costs among extreme LBW (<1000 g), very LBW (1000 and 1499 g), and moderate LBW (1500 and 2499 g) of $117,000, $84,000, and, $20,000, respectively. Maternal characteristics such as high prepregnancy weight, aboriginal status, and lower socioeconomic status were associated with higher HSU costs among the infants. LBW accounted for 7% of all infants but 37% of the total costs, amounting to $108 million annually. CONCLUSIONS: Compared with NBW infants, LBW infants consume more health resources not only in terms of initial hospitalization but also of re hospitalizations, outpatient, and physician visits during the first year of their life. Interventions targeting social determinants of health are required to improve birth weight outcomes in Alberta. PMID- 26148660 TI - Antithrombin Concentrate Use in Children Receiving Unfractionated Heparin for Acute Thrombosis. AB - OBJECTIVE: To characterize features of antithrombin concentrate (ATC) use in children receiving unfractionated heparin (UFH) therapy for acute thrombosis. STUDY DESIGN: All pediatric patients at Texas Children's Hospital who received ATC in the context of UFH therapy for acute thrombosis during February 2011 to May 2013 were analyzed. RESULTS: Fifty-one children received ATC during UFH therapy for acute thrombosis. Median age was 3 months (IQR 1 to 18 months). Clinical indications included venous (53%), arterial (37%), venous and arterial (6%), and intracardiac (4%) thrombosis. Median baseline antithrombin (AT) level was 61% and UFH dose was 26 U/kg/h. The median dose of ATC was 49.9 IU/kg (IQR 32.6 to 50.0 IU/kg). Although most patients (86%) did not undergo a change in UFH dose, there was a significant increase in both AT and anti-factor Xa level after the first dose of ATC (P < .001 for both). There was no correlation between ATC dose or increment in AT level above baseline and the achievement of targeted anticoagulation by anti-factor X activity level. Adverse bleeding events occurred in 10% of patients. CONCLUSIONS: There was a significant change in AT and anti factor Xa activity level after a single dose of ATC despite little to no change in dose of UFH. ATC appears to facilitate anticoagulation with UFH in some children with acute thrombosis but the degree of response is variable and dependent on factors identified in this study. Bleeding and other theoretical risks must be carefully considered. PMID- 26148661 TI - Linear Leukoplakia and Central Nervous System Lesions: A Clinical Clue to the Diagnosis of Hypomelanosis of Ito. PMID- 26148662 TI - Reduced Toxicity Conditioning and Allogeneic Hematopoietic Progenitor Cell Transplantation for Recessive Dystrophic Epidermolysis Bullosa. AB - Recessive dystrophic epidermolysis bullosa is a severe, incurable, inherited blistering disease caused by COL7A1 mutations. Emerging evidence suggests hematopoietic progenitor cells (HPCs) can be reprogrammed into skin; HPC-derived cells can restore COL7 expression in COL7-deficient mice. We report two children with recessive dystrophic epidermolysis bullosa treated with reduced-toxicity conditioning and HLA-matched HPC transplantation. PMID- 26148663 TI - Electrocardiogram in Preparticipation Athletic Evaluations among Insured Youths. AB - OBJECTIVE: To retrospectively characterize electrocardiogram (ECG) use among preparticipation history and examinations (PPEs). STUDY DESIGN: Using the 2005 to 2010 MarketScan insurance database, we identified subjects aged 5-21 years with either a PPE with an ECG or a PPE alone, excluding those with known cardiac diagnoses. We described cardiology referrals and subspecialty testing within 180 days and cardiac diagnoses within 1 year of the PPE, and the costs of testing in each group. RESULTS: From 2005-2009, 503 304 PPEs occurred in 419 456 subjects, of which 8621 (2%) included an ECG. ECG use increased from 12-20 per 1000 PPEs from 2005-2009. Females, lower socioeconomic status, and rural settings were associated with fewer ECGs. Thirteen percent of PPEs with ECG and 0.5% of PPEs alone led to a cardiology referral. After PPEs with ECG, cardiac disease was identified in 18% (2% sports-limiting); after PPEs alone, cardiac disease was identified in 0.5% (0.03% sports-limiting). The PPE had a sensitivity of 44% and a specificity of 98.6% of identifying cardiac disease. The total reimbursement cost of PPEs plus testing was $80 396 464 ($160 per PPE). CONCLUSIONS: These real world data demonstrate that community providers selectively use the ECG as part of the PPE with a high rate of identification of cardiac disease. Mass ECG screening would need to be more efficient at identifying disease than this selective approach. PMID- 26148664 TI - Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18. AB - Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 A resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development. PMID- 26148665 TI - Biological relevance of decamethylcyclopentasiloxane (D5) induced rat uterine endometrial adenocarcinoma tumorigenesis: Mode of action and relevance to humans. AB - Decamethylcyclopentasiloxane (D5) is a cyclic siloxane used in the production and formulation of consumer products with potential exposure to manufacturing workers, consumer, and the general public. Following a combined 2-year inhalation chronic bioassay performed in Fischer 344 (F344) rats, an increase in uterine endometrial adenocarcinomas was noted at the highest concentration to which animals were exposed. No other neoplasms were detected. In this study, a dose of 160 ppm produced an incidence of 8% endometrial adenocarcinomas. Based on a number of experimental studies with D5, the current manuscript examines the biological relevance and possible modes of action for the uterine endometrial adenocarcinomas observed in the rat following chronic exposure to D5. Variable rates of spontaneous uterine endometrial adenocarcinomas have been reported for untreated F344 CrlBr rats. As such, we concluded that the slight increase in uterine endometrial adenocarcinomas observed in the D5 chronic bioassay might not be the result of D5 exposure but may be related to variability of the spontaneous tumor incidence in this strain of rat. However, if the uterine endometrial adenocarcinomas are related to D5-exposure, alteration in the estrous cycle in the aging F344 rat is the most likely mode of action. D5 is not genotoxic or estrogenic. The alteration in the estrous cycle is caused by a decrease in progesterone with an increase in the estrogen:progesterone ratio most likely induced by a decrease in prolactin concentration. Available data support that exposure to D5 influences prolactin concentration. Although the effects on prolactin concentrations in a number of experiments were not always consistent, the available data support the conclusion that D5 is acting via a dopamine receptor agonist-like mechanism to alter the pituitary control of the estrous cycle. In further support of this mode of action, studies in F344 aged animals showed that the effects of D5 on estrous cyclicity produced a response consistent with a dopamine-like effect and further suggest that D5 is accelerating the aging of the reproductive endocrine system in the F344 rat utilized in this study. This mode of action for uterine endometrial adenocarcinoma tumorigenesis is not relevant for humans. PMID- 26148666 TI - Phenomenology and the life sciences: Clarifications and complementarities. AB - This paper first clarifies phenomenology in ways essential to demonstrating its basic concern with Nature and its recognition of individual and cultural differences as well as commonalities. It furthermore clarifies phenomenological methodology in ways essential to understanding the methodology itself, its purpose, and its consequences. These clarifications show how phenomenology, by hewing to the dynamic realities of life itself and experiences of life itself, counters reductive thinking and "embodiments" of one kind and another. On the basis of these clarifications, the paper then turns to detailing conceptual complementarities between phenomenology and the life sciences, particularly highlighting studies in coordination dynamics. In doing so, it brings to light fundamental relationships such as those between mind and motion and between intrinsic dynamics and primal animation. It furthermore highlights the common concern with origins in both phenomenology and evolutionary biology: the history of how what is present is related to its inception in the past and to its transformations from past to present. PMID- 26148667 TI - Natural history of Brugada syndrome in a patient with congenital heart disease. AB - Risk stratification of sudden death in patients with Brugada syndrome (BrS) is a controversial issue, and there is currently no consensus on the best method. Examination of data from the natural history of the disease is of fundamental importance and may help to identify relatives at risk. At the same time, study of the genetic mutations responsible for the disease may also contribute to risk stratification of the syndrome, enabling identification of asymptomatic relatives carrying mutations. This paper presents the case of a young man, aged 26, monitored as a pediatric cardiology outpatient from birth for a simple structural heart defect not requiring surgery. Analysis of the evolution of the patient's electrocardiogram revealed the appearance, at the age of 20, of a pattern compatible with type I BrS. Following an episode of syncope and induction of polymorphic ventricular tachycardia in the electrophysiological study, a cardioverter-defibrillator was implanted. One year later, a single shock terminated an episode of ventricular fibrillation. A molecular study of the SCN5A gene identified a rare mutation, c.3622G>T (p.Glu1208X), recently described and associated with more severe phenotypes in patients with BrS, as in the case presented. PMID- 26148668 TI - Failure to deliver a shock in a dual-chamber implantable cardioverter defibrillator: a case report. AB - INTRODUCTION: Inappropriate implantable cardioverter-defibrillator (ICD) therapies due to supraventricular tachyarrhythmia (SVT) are a common problem. The authors report this case to warn of a possible detection problem and subsequent failure of deliver appropriate therapy in patients with atrial fibrillation (AF) and a dual-chamber ICD using the PARAD+ algorithm. To our knowledge this is the first reported case of failure to deliver a shock in a dual-chamber ICD due to the PARAD+ algorithm. CASE REPORT: The authors present a case of a 68-year-old Caucasian man with permanent AF and a dual-chamber Sorin Paradym ICD with the PARAD+ algorithm, who presented an episode of sustained ventricular tachycardia (VT). The ICD did not store the event and did not delivery a therapy, although the heart rate curve was consistent with an episode of VT. No evidence of system dysfunction was found. CONCLUSION: Due to simultaneous occurrence of VT and AF rhythms and alternation in rhythm classification by the PARAD+ algorithm the number of cycles needed to diagnose VT was not achieved and no therapy was delivered. In patients with permanent or long-term persistent AF with a dual chamber ICD using the PARAD+ algorithm, discrimination should be based only on the ventricular channel. In patients with paroxysmal or persistent recurrent AF the risk of not delivering VT therapy must be weighed against the risk of inappropriate therapy. PMID- 26148669 TI - Cardiac papillary fibroelastoma. PMID- 26148670 TI - Commentary on 'MRI with a Weak Albumin Binding Contrast Agent can Unmask Additional Endoleaks in Patients with Enlarging Aneurysm After EVAR'. PMID- 26148671 TI - Commentary on 'endovascular aneurysm sealing for infrarenal abdominal aortic aneurysms: 30 day outcomes of 105 patients in a single centre'. PMID- 26148672 TI - Quantitative and qualitative analysis of the novel antitumor 1,3,4-oxadiazole derivative (GLB) and its metabolites using HPLC-UV and UPLC-QTOF-MS. AB - Fructose-based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) is a novel antitumor agent and belongs to glycosylated spiro-heterocyclic oxadiazole scaffold derivative. This research first reported a simple, specific, sensitive and stable high performance liquid chromatography-ultraviolet detector (HPLC-UV) method for the quantitative determination of GLB in plasma. In this method, the chromatographic separation was achieved with a reversed phase C18 column. The calibration curve for GLB was linear at 300 nm. The lower limit of quantification was 10 ng/mL. The precision, accuracy and stability of the method were validated adequately. This method was successfully applied to the pharmacokinetic study in rats for detection of GLB after oral administration. Moreover, the structures of parent compound GLB and its two major metabolites M1 and M2 were identified in plasma using an ultra performance liquid chromatography-electrospray ionization quadrupole-time of flight- mass spectrometry (UPLC-ESI-QTOF-MS) method. Our results indicated that the di-hydroxylation (M1) and hydroxylation (M2) of GLB are the major metabolites. In conclusion, the present study provided valuable information on an analytical method for the determination of GLB and its metabolites in rats, can be used to support further developing of this antitumor agent. PMID- 26148673 TI - Negative Expression of CPSF2 Predicts a Poorer Clinical Outcome in Patients with Papillary Thyroid Carcinoma. AB - BACKGROUND: The BRAF(V600E) mutation is a promising prognostic biomarker for patients with papillary thyroid carcinoma (PTC), but its prevalence differs widely among different geographic regions. A recent study reported that loss of the Cleavage and Polyadenylation Specificity Factor Subunit 2 (CPSF2) gene was associated with increased cellular invasion, cancer stem cells, and aggressiveness of PTC. This study aimed at evaluating CPSF2 protein expression as a prognostic marker for PTC in a region with a high prevalence of the BRAF(V600E) mutation, Korea. METHODS: This study included 159 patients with classical PTC who underwent a total thyroidectomy and received ablative doses of (131)I. The expression of CPSF2 protein was evaluated by immunohistochemistry and graded semi quantitatively. The presence of the BRAF(V600E) mutation was evaluated by direct sequencing. RESULTS: Negative protein expression of CPSF2 was observed in 34 (21.3%) of the 159 PTCs. In multivariate analysis, negative CPSF2 expression was significantly associated with cervical lymph node metastasis (odds ratio [OR]=2.56, p=0.28), and distant metastasis (OR=3.48, p=0.02). After adjusting for age, sex, tumor size, extrathyroidal invasion, lymphovascular invasion, and the BRAF(V600E) mutation, the CPSF2-negative group had a significantly lower recurrence-free survival compared to the CPSF2-positive group (hazard ratio=2.14, p=0.03). CONCLUSION: Negative protein expression of CPSF2 is independently associated with a poor clinical outcome in PTC. CPSF2 could be a useful prognostic marker for PTC in regions with a high prevalence of the BRAF(V600E) mutation. PMID- 26148674 TI - Electrochemical immunosensor based on bismuth nanocomposite film and cadmium ions functionalized titanium phosphates for the detection of anthrax protective antigen toxin. AB - Bacillus anthracis is a bioterrorism agent classified by the Centers for Disease Control and Prevention (CDC). Herein, a novel electrochemical immunosensor for the sensitive, specific and easy detection of anthrax protective antigen (PA) toxin in picogram concentration was developed. The immunosensor consists of (i) a Nafion-multiwall carbon nanotubes-bismuth nanocomposite film modified glassy carbon electrodes (BiNPs/Nafion-MWCNTs/GCE) as a sensing platform and (ii) titanium phosphate nanoparticles-cadmium ion-mouse anti-PA antibodies (TiP-Cd(2+) MalphaPA antibodies) as signal amplification tags. Scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), thermogravimmetric analysis (TGA), Fourier transform-infra red spectroscopy (FT-IR), zeta-potential analysis, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were employed to characterize the synthesized TiP nanoparticles and modified electrode surfaces. The immunosensing performance of BiNPs/Nafion-MWCNTs/GCE was evaluated based on sandwich immunoassay protocol. A square wave voltammetry (SWV) scan from -1.2 to -0.3 V in HAc-NaAc buffer solution (pH 4.6) without stripping process was performed to record the electrochemical responses at -0.75 V corresponding to high content of Cd(2+) ions loaded in TiP nanoparticles for the measurement of PA toxin. Under optimal conditions, the currents increased with increasing PA toxin concentrations in spiked human serum samples and showed a linear range from 0.1 ng/ml to 100 ng/ml. The limit of detection of developed immunosensor was found to be 50 pg/ml at S/N=3. The total time of analysis was 35 min. PMID- 26148675 TI - On-chip porous microgel generation for microfluidic enhanced VEGF detection. AB - Advances in medical diagnostics and personalized therapy require sensitive and rapid measurement of minute amounts of proteins from patients. Standard ELISA is difficult to prepare and involves lengthy protocols. Here we report a novel method using capture antibody immobilized porous poly (ethylene) glycol diacrylate (PEGDA) hydrogel microspheres to enable high sensitivity VEGF detection in arrayed microfluidics. Our technique incorporates antibody encapsulation, trapping, and flow perfusion on a single device. We showed that the convergence of tunable porous hydrogel with efficient microfluidics improved the sensitivity of the assay. The detection limit of this microfluidic porous microgel based assay was 0.9 pg/mL, with only 1+ hour of assay time, demonstrating a novel assay that exceeded conventional technologies in terms of sensitivity and speed. PMID- 26148676 TI - A triple-dimensional sensing chip for discrimination of eight antioxidants based on quantum dots and graphene. AB - A triple-dimensional sensing chip is developed based on simultaneous utilization of fluorescence (FL), electrochemical (ECL) and mass-sensitivity (MS) properties of a novel nanocomposites. The sensing nanomaterial is composed of CdSe/ZnS quantum dots (QDs) and graphene through a one-pot room-temperature reverse microemulsion polymerization. Here, full integration of QDs and graphene on one chip provides triple-dimensional sensing signals. It enables quick and accurate discrimination of eight analytes in a "lab-on-a-nanomaterial" approach and notably improves the overall sensor performance. Unknown samples randomly taken from the training set at concentrations of 0.7 MUM are successfully classified by principal component analysis (PCA) with accuracies of 92.5%, compared with the high performance liquid chromatography (HPLC) method. We further apply it to discriminate eight antioxidants from real oil samples, and explore the mechanism. PMID- 26148677 TI - An NKX3.1 binding site polymorphism in the l-plastin promoter leads to differential gene expression in human prostate cancer. AB - The L-plastin gene is involved in the invasion and metastasis of prostate cancer. However, the molecular mechanisms underlying L-plastin transcription are unclear. We hypothesize that the occurrence of polymorphic genetic variations in the L plastin promoter might affect an individual's susceptibility to prostate cancer. In this study, we identified a single nucleotide polymorphism (SNP) at position 1,687 in the L-plastin promoter by genotype sequencing. The SNP -1,687 showed different transcriptional activity in the luciferase assay in vitro. The TRANSFAC software was applied to predict the multiple cis-elements, and luciferase assay was used to further identify the L-plastin regulatory region. We performed EMSAs, supershift assays and ChIP-qPCR demonstrated that the transcriptional suppressor NKX3.1 binds to the SNP site of the L-plastin promoter. SNP -1,687 (T/T) led to an increase in the affinity of NKX3.1 for L-plastin promoter, resulted in lower levels of L-plastin RNA and protein expression. Furthermore, we collected and sequenced samples from 640 individuals (372 prostate cancer patients and 268 healthy controls) from 2000 to 2013. The results showed that SNP -1,687 (T/T) occurred more frequently in the healthy individuals than that in the prostate cancer patients compared to SNP -1,687 (C/C). Similarly, SNP -1,687 (T/T) genotype occurred more frequently compared to SNP -1,687 (C/C) genotype in the patients with low and moderately differentiated tumors. In conclusion, SNP 1,687, located in the NKX3.1 binding site within the L-plastin promoter, might reduce the expression of L-plastin and potentially decrease the tumorigenesis and progression of prostate cancer. This SNP could be a potential prognostic factor for prostate cancer. PMID- 26148678 TI - Parents' beliefs and knowledge about the management of acute otitis media: a qualitative study. AB - BACKGROUND: Acute otitis media is a common reason for antibiotic prescribing, despite strong evidence that antibiotics provide minimal benefit. Studies have demonstrated that patients' (or parents') expectations of antibiotics often influence general practitioners' (GPs) decision to prescribe antibiotics, but few have explored parents' expectations of the management of infections in children, or which factors influence the development of these expectations. This study aimed to explore parents' knowledge and beliefs about the management of acute otitis media in children. METHODS: Individual semi-structured interviews were conducted with 15 parents of children who had recently presented to their GP with acute otitis media. Parents were recruited at childcare centres or playgroups in Brisbane, Australia. RESULTS: Many parents did not have an accurate understanding of what causes acute otitis media. GPs were primarily consulted for the management of symptoms such as pain and fever. Others specifically wanted reassurance or were concerned about hearing loss. Most parents assumed that antibiotics were the best treatment option. Parents' perceptions about the best treatment were mainly based on their previous experience and the advice of the GP. Pain relief medications, such as paracetamol and non-steroidal anti inflammatory drugs, were not considered by parents to be sufficient treatment on their own. CONCLUSION: There is discrepancy between parents' beliefs and expectations of management of acute otitis media and the evidence-based recommendations. This study provides insights into parents' expectations of management of acute otitis media, which may help inform clinicians about perceptions and misperceptions that may be valuable to elicit and discuss. PMID- 26148679 TI - Properties and Application Perspective of Hybrid Titania-Silica Patterns Fabricated by Inkjet Printing. AB - A hybrid titania-silica cold-setting sol has been developed that can be deposited onto a wide variety of surfaces without the need for high-temperature fixing and that is suitable for material printing deposition. Thin hybrid titania-silica coatings were patterned onto glass and PET substrates by inkjet printing. Well defined hybrid titania-silica patterns, with thicknesses ranging from 40 to 400 nm, were fabricated by overprinting 1 to 10 layers. Excellent mechanical, optical, and photocatalytic properties were observed, making the reported material well suited for the fabrication of transparent self-cleaning coatings both on mineral and organic substrates. The printed patterns exhibit photoelectrochemical activity that can be further improved by thermal or photonic curing. A concept of fully printed interdigitated photoelectrochemical cells on flexible PET substrates utilizing the reported hybrid photocatalyst is disclosed as well. PMID- 26148680 TI - Effects of pravastatin, phytosterols, and combination therapy on lipid profile in HIV-infected patients: an open-labelled, randomized cross-over study. AB - BACKGROUND: To determine the effects of 40 mg of pravastatin, 2 g of phytosterols, and combination therapy on lipid profiles and to compare the reduction of LDL cholesterol between combination therapy and monotherapy. METHODS: Thirty-six HIV-infected patients treated with ARVs who had high LDL cholesterol levels but no current usage of any lipid-lowering agents were enrolled into the open-labelled, randomized, cross-over study. All patients were assigned randomly into one of four intervention groups: (1) pravastatin 40 mg cross-over to the combination of pravastatin 40 mg and phytosterols 2 g (combination group), (2) the combination group cross-over to pravastatin 40 mg, (3) phytosterols 2 g cross-over to the combination group, and (4) the combination group cross-over to phytosterols 2 g. Each active treatment lasted 4 weeks with a wash-out period of 4 weeks. RESULTS: The baseline mean TC, TG, HDL-c, and LDL-c levels in 36 HIV patients were 248.09 +/- 34.73, 172.36 +/- 125.44, 54.92 +/- 16.67, and 175.13 +/- 29.00 mg/dl, respectively. Pravastatin, phytosterols, and combination therapy reduced TC and LDL-c but TG and HDL-c were not significantly different from the baselines. The mean LDL-c reductions in the pravastatin, phytosterols, and the combination groups were 28.76 +/- 9.32, 9.12 +/- 7.84, and 27.08 +/- 15.58%, respectively. The LDL-c levels in the pravastatin and combination groups were reduced more than in the phytosterols group (p < 0.01). There was no difference in the LDL-c reduction between the combination and pravastatin monotherapy groups (-25.61 +/- 10.43 vs. -28.12 +/- 14.07%, p = 0.555). CONCLUSION: Pravastatin had moderate potency on LDL-c lowering in HIV patients but could not bring LDL-c to goal. Adding phytosterols to pravastatin for a 4-week duration could not demonstrate any additional lipid-lowering effect TRIAL REGISTRATION: Thai Clinical Trial Registry: TCTR20150126002 date: January 23, 2015. PMID- 26148681 TI - ComOn Coaching: Study protocol of a randomized controlled trial to assess the effect of a varied number of coaching sessions on transfer into clinical practice following communication skills training. AB - BACKGROUND: Communication skills training has proven to be an effective means to enhance communication of health care professionals in oncology. These effects are well studied in standardized settings. The question of transferring these skills into clinical consultations remains open. We build up on a previous developed training concept consisting of a workshop and coaching. This training achieved a medium effect size in two studies with standardized patients. In the current study, we expanded and manualized the coaching concept, and we will evaluate effects of a varied number of coaching sessions on real clinical consultations. Our aim is to determine how much coaching oncologists need to transfer communication skills into clinical practice. METHODS/DESIGN: Physicians of two German medical centers will participate in a workshop for communication skills and will be randomized to either a group with one coaching session or a group with four coaching sessions following the workshop. The participation is voluntary and the physicians will receive medical education points. Consultations held by the participating physicians with actual patients who gave their informed consent will be filmed at three time points. These consultations will be evaluated by blinded raters using a checklist based on the training content (primary outcome). Secondary outcomes will be the self-evaluated communication competence by physicians and an evaluation of the consultations by both physicians and patients. DISCUSSION: We will evaluate our communication training concept on three levels - rater, physician and patient - and concentrate on the transfer of communication skills into real life situations. As we emphasize the external validity in this study design, limitations will be expected due to heterogeneity of data. With this study we aim to gain data on how to improve communication skills training that will result in better patient outcomes. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004385 . PMID- 26148683 TI - Structural phase transitions and magnetic and spectroscopic properties of the double perovskites Sr2Co1-xMgxTeO6 (x = 0.1, 0.2 and 0.5). AB - The structural and magnetic properties of a series of ordered double perovskites with the formula Sr(2)Co(1-x)Mg(x)TeO(6) (x = 0.1, 0.2 and 0.5) are investigated by X-ray diffraction, low temperature neutron diffraction, electron paramagnetic resonance and magnetic susceptibility. The progressive substitution of the paramagnetic Co(2+) high spin ion by the diamagnetic Mg(2+), of about the same size, induces changes in the room temperature crystal structure, from a distorted P2(1)/n phase for the undoped Sr(2)CoTeO(6) oxide to the I4/m of the end member (Sr(2)MgTeO(6)). These perovskites experience structural transitions on heating, the temperature at which the transitions occur being smaller as x increases. The novel approach of mode-crystallography is used for the analysis. All oxides show antiferromagnetic exchange interactions between Co(2+) ions but the long range antiferromagnetic order is not achieved for the phase with x = 0.5. The low temperature neutron diffraction data have been evaluated using a full symmetry analysis. Results are consistent with an unquenched orbital contribution of a high spin Co(2+) ion. PMID- 26148682 TI - Arterial endothelial methylome: differential DNA methylation in athero susceptible disturbed flow regions in vivo. AB - BACKGROUND: Atherosclerosis is a heterogeneously distributed disease of arteries in which the endothelium plays an important central role. Spatial transcriptome profiling of endothelium in pre-lesional arteries has demonstrated differential phenotypes primed for athero-susceptibility at hemodynamic sites associated with disturbed blood flow. DNA methylation is a powerful epigenetic regulator of endothelial transcription recently associated with flow characteristics. We investigated differential DNA methylation in flow region-specific aortic endothelial cells in vivo in adult domestic male and female swine. RESULTS: Genome-wide DNA methylation was profiled in endothelial cells (EC) isolated from two robust locations of differing patho-susceptibility:--an athero-susceptible site located at the inner curvature of the aortic arch (AA) and an athero protected region in the descending thoracic (DT) aorta. Complete methylated DNA immunoprecipitation sequencing (MeDIP-seq) identified over 5500 endothelial differentially methylated regions (DMRs). DMR density was significantly enriched in exons and 5'UTR sequences of annotated genes, 60 of which are linked to cardiovascular disease. The set of DMR-associated genes was enriched in transcriptional regulation, pattern specification HOX loci, oxidative stress and the ER stress adaptive pathway, all categories linked to athero-susceptible endothelium. Examination of the relationship between DMR and mRNA in HOXA genes demonstrated a significant inverse relationship between CpG island promoter methylation and gene expression. Methylation-specific PCR (MSP) confirmed differential CpG methylation of HOXA genes, the ER stress gene ATF4, inflammatory regulator microRNA-10a and ARHGAP25 that encodes a negative regulator of Rho GTPases involved in cytoskeleton remodeling. Gender-specific DMRs associated with ciliogenesis that may be linked to defects in cilia development were also identified in AA DMRs. CONCLUSIONS: An endothelial methylome analysis identifies epigenetic DMR characteristics associated with transcriptional regulation in regions of atherosusceptibility in swine aorta in vivo. The data represent the first methylome blueprint for spatio-temporal analyses of lesion susceptibility predisposing to endothelial dysfunction in complex flow environments in vivo. PMID- 26148684 TI - A cross-sectional survey of the effect on emerging adults living with a depressed parent. AB - A parent who is depressed is physically present, but may be psychologically absent, or different to their children. Changes in the parent-child relationship, feelings of loss, and increased stress can occur for the child. These factors can impair psychosocial well-being throughout the child's upbringing, and the effects might impact that child the most in their transition to adulthood. The aim of this exploratory study was to examine factors experienced while growing up with a depressed parent that might contribute to the current psychosocial well-being of emerging adults (individuals between the ages of 18 and 25) using ambiguous loss theory as a theoretical lens. A cross-sectional, correlational design with multiple regression analysis was used to examine relationships between emerging adults' (n = 120) perceptions of retrospective duration and understanding of parent's depression, caregiving, stress, social support, hope, and boundary ambiguity and current psychosocial well-being. Experiencing hope, stress, and then the length of parent's depression during their upbringing were the most predictive variables for emerging adult psychosocial well-being. Findings from this study will help mental health professionals better understand factors contributing to outcomes for this population. The knowledge to be gained is important for developing or refining age and developmentally appropriate interventions aimed at improving outcomes of adult children of depressed parents. PMID- 26148685 TI - Risk factors, complications and survival after upper abdominal surgery: a prospective cohort study. AB - BACKGROUND: Preoperative weight loss and abnormal serum-albumin have traditionally been associated with reduced survival. More recently, a correlation between postoperative complications and reduced long-term survival has been reported and the significance of the relative proportion of skeletal muscle, visceral and subcutaneous adipose tissue has been examined with conflicting results. We investigated how preoperative body composition and major non-fatal complications related to overall survival and compared this to established predictors in a large cohort undergoing upper abdominal surgery. METHODS: From 2001 to 2006, 447 patients were included in a Norwegian multicenter randomized controlled trial in major upper abdominal surgery. Patients were now, six years later, analyzed as a single prospective cohort and overall survival was retrieved from the National Population Registry. Body composition indices were calculated from CT images taken within three months preoperatively. RESULTS: Preoperative serum-albumin <35 g/l (HR = 1.52, p = 0 .014) and weight loss >5 % (HR = 1.38, p = 0.023) were independently associated with reduced survival. There was no association between any of the preoperative body composition indices and reduced survival. Major postoperative complications were independently associated with reduced survival but only as long as patients who died within 90 days were included in the analysis. CONCLUSIONS: Our study has confirmed the robust significance of the traditional indicators, preoperative serum-albumin and weight loss. The body composition indices did not prove beneficial as global indicators of poor prognosis in upper abdominal surgery. We found no association between non fatal postoperative complications and long-term survival. PMID- 26148687 TI - Lactobacillus casei Low-Temperature, Dairy-Associated Proteome Promotes Persistence in the Mammalian Digestive Tract. AB - We found that incubation of probiotic Lactobacillus casei BL23 in milk at 4 degrees C prior to ingestion increased its survival in the mammalian digestive tract. To investigate the specific molecular adaptations of L. casei to milk, we used tandem mass spectrometry to compare proteins produced by L. casei BL23 at 4 degrees C in milk to those in exponential and stationary phase cells in laboratory culture medium at either 37 or 4 degrees C. These comparisons revealed a core of expressed L. casei proteins as well as proteins produced in either a growth-phase or temperature-specific manner. In total, 205 L. casei proteins were uniquely expressed or detected in higher abundance specifically as a result of incubation in milk and included an over-representation of proteins for cell surface modification, fatty acid metabolism, amino acid transport and metabolism, and inorganic ion transport. Genes for DltD (d-alanine transfer protein), FabH (3-oxoacyl-ACP synthase), RecA (recombinase A), and Sod (superoxide dismutase) were targeted for inactivation. The competitive fitness of the mutants was altered in the mouse intestine compared with wild-type cells. These results show that the food matrix can have a profound influence on dietary (probiotic) bacteria and their functional significance in the mammalian gut. PMID- 26148688 TI - A study on the role and importance of irrigation management in integrated river basin management. AB - The purpose of this paper is to identify the role and the importance of irrigation management in integrated river basin management during arid and semi arid conditions. The study has been conducted at Buyuk Menderes Basin which is located in southwest of Turkey and where different sectors (irrigation, drinking and using, industry, tourism, ecology) related to the use and distribution of water sources compete with each other and also where the water demands for important ecological considerations is evaluated and where the river pollution has reached important magnitudes. Since, approximately 73% of the water resources of the basin are utilized for irrigation; as a result, irrigation management becomes important for basin management. Irrigation operations have an effect on basin soil resources, water users, and environmental and ecological conditions. Thus, the determination of the role and importance of irrigation management require an integrated and interdisciplinary approach. In the studies conducted in Turkey, usually the environmental reactions have been analyzed in the basin studies and so the other topics related to integrated river basin management have not been taken into account. Therefore, this study also is to address these existing gaps in the literature and practice. PMID- 26148686 TI - The dynamic epitranscriptome: A to I editing modulates genetic information. AB - Adenosine to inosine editing (A to I editing) is a cotranscriptional process that contributes to transcriptome complexity by deamination of adenosines to inosines. Initially, the impact of A to I editing has been described for coding targets in the nervous system. Here, A to I editing leads to recoding and changes of single amino acids since inosine is normally interpreted as guanosine by cellular machines. However, more recently, new roles for A to I editing have emerged: Editing was shown to influence splicing and is found massively in Alu elements. Moreover, A to I editing is required to modulate innate immunity. We summarize the multiple ways in which A to I editing generates transcriptome variability and highlight recent findings in the field. PMID- 26148689 TI - Application of multiple toxicity tests in monitoring of landfill leachate treatment efficiency. AB - Leachate from a closed landfill used for co-disposal of municipal and tannery waste was submitted to coagulation treatment, air stripping, adsorption on granular activated carbon, and Fenton oxidation with the aim to reduce toxicity of the leachate. Optimal operational conditions for each process were identified. The performance of the treatment was monitored by determination of organic matter (COD, DOC, BOD5), inorganic components (N-NH4(+), Cl(-), alkalinity, metals), organic compounds (BTEX, PAHs, PCBs, OCPs) while changes in toxicity were followed by multiple toxicity tests. Among the applied treatment techniques, adsorption on granular activated carbon was the most efficient method for removal of organic matter and metals while air stripping was the most efficient for removal of N-NH4(+) and reduction of toxicity. Lower reduction of organic matter content and toxicity was obtained during coagulation treatment. Fenton oxidation was effective for removal of COD; however, it negatively affected toxicity reduction. The combination of adsorption on granular activated carbon and air stripping led to an appreciable reduction of organic and inorganic pollutants and to leachate detoxification. Application of bioassays was helpful for assessing suitability of treatment methods and demonstrated that they are, together with physicochemical parameters, an indispensable part for monitoring of treatment efficiency. PMID- 26148691 TI - Spatial and climatic patterns of the relative abundance of poisonous vs. non poisonous plants across the Northern Tibetan Plateau. AB - It is the most serious challenge to promote degraded grassland recovery currently facing the developing Tibetan Autonomous Region. We conducted field surveys of 75 grazing sites between 2009 and 2012 across the Northern Tibetan Plateau and described the spatial and climatic patterns of the occurrence of poisonous plants. Our results showed lower ratios of species richness (SprRatio), coverage (CovRatio), and biomass (BioRatio) of non-poisonous vs. poisonous plants in the semi-arid alpine steppe zone, where the growing season precipitation (GSP) is between 250 and 350 mm; however, this result is in contrast to the relatively wetter meadow (GSP >350 mm) and much drier desert-steppe (GSP <250 mm) communities. Results from generalized additive models (GAMs) further confirmed that precipitation is primarily responsible for the initially decreasing and then increasing tendency of compositional ratios of non-poisonous to poisonous species. The wide confidence bands at GSP <250 mm indicated that precipitation is not an effective indicator for predicting compositional changes in desert-steppe communities. When mean annual livestock grazing pressure was incorporated into the optimal GAMs, the model performance improved: the Akaike information criterion (AIC) decreased by 1.20 for SprRatio and 3.09 for BioRatio, and the deviance explained (R (2)) increased by 6.0% for SprRatio and 3.6% for BioRatio. Therefore, more detailed information on grazing disturbance (timing, frequency, and density) should be collected to disentangle the relative contribution of climate change and grazing activities to changes in community assembly and ecological functions of alpine grasslands on the Northern Tibetan Plateau. PMID- 26148690 TI - Chiral xenobiotics bioaccumulations and environmental health prospectives. AB - The chiral xenobiotics are very dangerous for all of us due to the different enantioselective toxicities of the enantiomers. Besides, these have different enantioselective bioaccumulations and behaviors in our body and other organisms. It is of urgent need to understand the enantioselective bioaccumulations, toxicities, and the health hazards of the chiral xenobiotics. The present article describes the classification, sources of contamination, distribution, enantioselective bioaccumulation, and the toxicities of the chiral xenobiotics. Besides, the efforts are also made to discuss the prevention and remedial measures of the havoc of the chiral xenobiotics. The challenges of the chiral xenobiotics have also been highlighted. Finally, future prospectives are also discussed. PMID- 26148692 TI - Resolving future fire management conflicts using multicriteria decision making. AB - Management strategies to reduce the risks to human life and property from wildfire commonly involve burning native vegetation. However, planned burning can conflict with other societal objectives such as human health and biodiversity conservation. These conflicts are likely to intensify as fire regimes change under future climates and as growing human populations encroach farther into fire prone ecosystems. Decisions about managing fire risks are therefore complex and warrant more sophisticated approaches than are typically used. We applied a multicriteria decision making approach (MCDA) with the potential to improve fire management outcomes to the case of a highly populated, biodiverse, and flammable wildland-urban interface. We considered the effects of 22 planned burning options on 8 objectives: house protection, maximizing water quality, minimizing carbon emissions and impacts on human health, and minimizing declines of 5 distinct species types. The MCDA identified a small number of management options (burning forest adjacent to houses) that performed well for most objectives, but not for one species type (arboreal mammal) or for water quality. Although MCDA made the conflict between objectives explicit, resolution of the problem depended on the weighting assigned to each objective. Additive weighting of criteria traded off the arboreal mammal and water quality objectives for other objectives. Multiplicative weighting identified scenarios that avoided poor outcomes for any objective, which is important for avoiding potentially irreversible biodiversity losses. To distinguish reliably among management options, future work should focus on reducing uncertainty in outcomes across a range of objectives. Considering management actions that have more predictable outcomes than landscape fuel management will be important. We found that, where data were adequate, an MCDA can support decision making in the complex and often conflicted area of fire management. PMID- 26148693 TI - Image-guided techniques improve accuracy of mosaic arthroplasty. AB - PURPOSE: Mosaic arthroplasty is a surgical technique in which a set of cylindrical osteochondral grafts is transplanted from non-load-bearing areas of the joint to repair damaged articular cartilage. Incongruity between the graft surface and the adjacent cartilage at the repair site results in inferior clinical outcomes. This paper compares technical outcome using three mosaic arthroplasty techniques (conventional, optoelectronic, and patient-specific template) on femur models. METHODS: Three distinct sets of femur models with defects were created. Preoperatively, the harvest and delivery sites were planned using custom software. Five orthopedic surgeons were recruited; each surgeon performed each of the three surgical techniques on each of the three bone models with defect. During the optoelectronic trials, the instrument position and orientation were tracked and superimposed onto the surgical plan. For the patient specific template trials, plastic templates were manufactured to fit over the defects with cylindrical holes to guide the surgical tools according to the plan. Postoperatively, the femur models were computer tomography and laser scanned. Several measures were made to compare surgical techniques: operative time; surface congruency; defect coverage; graft surface area that is proud or recessed; air volume below the grafts; and distance and angle of the grafts from the surgical plan. RESULTS: The patient-specific template and optoelectronic techniques resulted in improved surface congruency, defect surface coverage, and below-graft air gap volume in comparison with the conventional technique. However, the conventional technique had a shorter operative time. CONCLUSIONS: Image-guided techniques can improve the accuracy of mosaic arthroplasty, which could result in better clinical outcomes. PMID- 26148694 TI - Patient-specific instrument can achieve same accuracy with less resection time than navigation assistance in periacetabular pelvic tumor surgery: a cadaveric study. AB - PURPOSE: Inaccurate resection in pelvic tumors can result in compromised margins with increase local recurrence. Navigation-assisted and patient-specific instrument (PSI) techniques have recently been reported in assisting pelvic tumor surgery with the tendency of improving surgical accuracy. We examined and compared the accuracy of transferring a virtual pelvic resection plan to actual surgery using navigation-assisted or PSI technique in a cadaver study. METHODS: We performed CT scan in twelve cadaveric bodies including whole pelvic bones. Either supraacetabular or partial acetabular resection was virtually planned in a hemipelvis using engineering software. The virtual resection plan was transferred to a CT-based navigation system or was used for design and fabrication of PSI. Pelvic resections were performed using navigation assistance in six cadavers and PSI in another six. Post-resection images were co-registered with preoperative planning for comparative analysis of resection accuracy in the two techniques. RESULTS: The mean average deviation error from the planned resection was no different ([Formula: see text]) for the navigation and the PSI groups: 1.9 versus 1.4 mm, respectively. The mean time required for the bone resection was greater ([Formula: see text]) for the navigation group than for the PSI group: 16.2 versus 1.1 min, respectively. CONCLUSIONS: In simulated periacetabular pelvic tumor resections, PSI technique enabled surgeons to reproduce the virtual surgical plan with similar accuracy but with less bone resection time when compared with navigation assistance. Further studies are required to investigate the clinical benefits of PSI technique in pelvic tumor surgery. PMID- 26148696 TI - Social relationships, depressive symptoms and suicidality in Korea: Examining mediating and moderating effects in men and women. AB - BACKGROUND: It has been widely recognized that social relationships and depressive symptoms predict suicidality. However, there are few empirical studies examining relationships among these three factors using an integrative approach. AIMS: This study aimed to examine the effects of perceived quality of social relationships and depressive symptoms on suicidality and to analyze whether the effect of perceived quality of social relationships on suicidality is mediated by depressive symptoms or whether the perceived quality of social relationships has a moderating effect on the relationship between depressive symptoms and suicidality in men and women. METHODS: The data were drawn from the 2012 Korean General Social Survey, a nationally representative survey. Multiple regression models and subsample analyses were conducted according to gender. RESULTS: A higher perceived quality of social relationships decreased suicidality while depressive symptoms increased suicidality. The effect of perceived quality of social relationships was partially mediated by depressive symptoms. Perceived quality of social relationships also significantly interacted with depressive symptoms, suggesting that the harmful effect of depressive symptoms was ameliorated as perceived quality of social relationships increased. A subsample analysis according to gender, however, indicated a significant gender difference in that the perceived quality of social relationships moderated the effect of depressive symptoms only in women. CONCLUSION: The findings suggest that enhanced quality of social relationships can protect people from suicidal risk and are more effective for women with depressive symptoms than for men with the same symptoms. PMID- 26148698 TI - [Personalized tumor therapy for gastrointestinal tumors]. AB - Personalized tumor therapy or more precisely tumor-specific therapy has now become established in routine clinical oncology. Particularly for solid tumors, the emerging knowledge about pathways and signaling networks allows the establishment of new targeted therapies and hopefully a continuous improvement in patient care. Targeted therapies are now established as the standard of care as single agents or in combination with chemotherapy. Using targeted therapies, substantial improvements regarding tumor response, median progression-free survival and median overall survival can be achieved for selected gastrointestinal tumors. However, these strategies also have novel side effects that need to be addressed. Importantly, valid (positive) predictive biomarkers are needed for a rational use of these novel compounds. This review article presents the current state of targeted tumor therapy for the diagnostics and therapy of gastrointestinal tumors and provides assistance in integrating the current knowledge into the routine clinical context. PMID- 26148697 TI - A time frame permissive for Protein Kinase D2 activity to direct angiogenesis in mouse embryonic stem cells. AB - The protein kinase D isoenzymes PKD1/2/3 are prominent downstream targets of PKCs (Protein Kinase Cs) and phospholipase D in various biological systems. Recently, we identified PKD isoforms as novel mediators of tumour cell-endothelial cell communication, tumour cell motility and metastasis. Although PKD isoforms have been implicated in physiological/tumour angiogenesis, a role of PKDs during embryonic development, vasculogenesis and angiogenesis still remains elusive. We investigated the role of PKDs in germ layer segregation and subsequent vasculogenesis and angiogenesis using mouse embryonic stem cells (ESCs). We show that mouse ESCs predominantly express PKD2 followed by PKD3 while PKD1 displays negligible levels. Furthermore, we demonstrate that PKD2 is specifically phosphorylated/activated at the time of germ layer segregation. Time-restricted PKD2-activation limits mesendoderm formation and subsequent cardiovasculogenesis during early differentiation while leading to branching angiogenesis during late differentiation. In line, PKD2 loss-of-function analyses showed induction of mesendodermal differentiation in expense of the neuroectodermal germ layer. Our in vivo findings demonstrate that embryoid bodies transplanted on chicken chorioallantoic membrane induced an angiogenic response indicating that timed overexpression of PKD2 from day 4 onwards leads to augmented angiogenesis in differentiating ESCs. Taken together, our results describe novel and time dependent facets of PKD2 during early cell fate determination. PMID- 26148699 TI - Validation study of the Forgotten Joint Score-12 as a universal patient-reported outcome measure. AB - PURPOSE: The Forgotten Joint Score-12 (FJS-12) is for patients to forget their artificial joint and is reportedly a useful patient-reported outcome tool for artificial joints. The purpose of this study was to determine whether the FJS-12 is as useful as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) or the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) in Japan. METHODS: All patients who visited our hospital's hip joint specialists following unilateral THA from August 2013 to July 2014 were evaluated. Medical staff members other than physicians administered three questionnaires. Items evaluated were (1) the reliability of the FJS-12 and (2) correlations between the FJS-12 and the total and subscale scores of the WOMAC or JHEQ. RESULTS: Of 130 patients, 22 were excluded. Cronbach's alpha coefficient was 0.97 for the FJS-12. The FJS-12 showed a significantly lower score than the WOMAC or JHEQ (p < 0.01). The FJS-12 was moderately correlated with the total WOMAC score (r = 0.522) and its subscale scores for "stiffness" (r = 0.401) and "function" (r = 0.539) and was weakly correlated with the score for "pain" (r = 0.289). The FJS-12 was favorably correlated with the total JHEQ score (r = 0.686) and its subscale scores (r = 0.530-0.643). CONCLUSION: The FJS-12 was correlated with and showed reliability similar to that of the JHEQ and WOMAC. The FJS-12, which is not affected by culture or lifestyle, may be useful in Japan. PMID- 26148700 TI - Ankle arthrodesis from lateral transfibular approach: analysis of treatment results of 23 feet treated by the modified Mann's technique. AB - BACKGROUND: The aim of the study was to analyze the results of treatment by ankle arthrodesis by modified Mann's technique. METHODS: The study included 23 patients, and a total of 23 feet were treated. Stabilization of arthrodesis was performed by two screws going from the sinus tarsi to the talus and tibia. Lateral part of the fibula was fixed with one or two screws to the talus and tibia. No additional medial approach to the ankle was performed. In 16 feet, arthrodesis was done due to secondary posttraumatic osteoarthritis, in five due to paralytic drop foot and in two due to osteoarthritis of unknown etiology. In 18 patients, the purpose of arthrodesis was also to correct the malalignment. The average age at operation was 46 (range 19-74) years. The average follow-up was 32 (range 12-69) months. RESULTS: At follow-up, the average AOFAS score was 76 points and subjective scale result 7.9 points. The correct alignment was not achieved in three feet. In one foot, fusion was not achieved and the patient needed repeated operation. CONCLUSIONS: The study has confirmed the effectiveness of the technique. PMID- 26148701 TI - The molecular classification of hereditary endocrine diseases. AB - Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases. PMID- 26148702 TI - Hyperosmolar coma in a patient with hypothalamic Langerhans cell histiocytosis. PMID- 26148703 TI - Health locus of control and cardiovascular risk factors in veterans with type 2 diabetes. AB - Perceptions of control impact outcomes in veterans with chronic disease. The purpose of this study was to examine the association between control orientation and clinical and quality of life (QOL) outcomes in male veterans with type 2 diabetes (T2DM). Cross-sectional study of 283 male veterans from a primary care clinic in the southeastern US. Health locus of control (LOC) was the main predictor and assessed using the Multidimensional Health LOC Scale. Clinical outcomes were glycosylated hemoglobin A1c (HbA1c), systolic and diastolic blood pressure, and low-density lipoprotein cholesterol (LDL-C). Physical (PCS) and mental (MCS) health component scores for QOL were assessed using the Veterans RAND 12-Item Health Survey. Unadjusted and adjusted multivariate analyses were performed to assess associations between LOC and outcomes. Unadjusted analyses showed internal LOC associated with HbA1c (beta = 0.036; 95% CI 0.001, 0.071), external LOC:powerful others inversely associated with LDL-C (beta = -0.794; 95% CI -1.483, -0.104), and external LOC:chance inversely associated with MCS QOL (beta = -0.418; 95% CI -0.859, -0.173). These associations remained significant when adjusting for relevant covariates. Adjusted analyses also demonstrated a significant relationship between external LOC:chance and PCS QOL (beta = 0.308; 95% CI 0.002, 0.614). In this sample of male veterans with T2DM, internal LOC was significantly associated with glycemic control, and external was significantly associated with QOL and LDL-C, when adjusting for relevant covariates. Assessments of control orientation should be performed to understand the perceptions of patients, thus better equipping physicians with information to maximize care opportunities for veterans with T2DM. PMID- 26148705 TI - A general approach to the synthesis and detailed characterization of magnetic ferrite nanocubes. AB - A general approach to the synthesis and detailed characterization of magnetic ferrite nanocubes were reported, where the nanocubes were synthesized by the thermal decomposition of metal-oleate complexes following a step-heating method. The doping ions were introduced during the precursor preparation by forming M(2+)/Fe(3+) oleate mixed complex (M(2+) = Fe(2+), Mn(2+), Zn(2+), Cu(2+), Ca(2+), and Mg(2+)). The mechanistic studies showed that the presence of sodium oleate in combination with step-heating was critical for the formation of the cubic shapes for the doped magnetic ferrites. The nanocubes were extensively characterized, including morphology and crytsal structure by advanced transmission electron microscopy, doping level and distribution by energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy, cation distribution within the spinel structures by Fourier transform infrared and Raman spectroscopy, and magnetic properties by alternating gradient magnetometer at room temperature. PMID- 26148704 TI - HEXIM1 induction is mechanistically involved in mediating anti-AML activity of BET protein bromodomain antagonist. PMID- 26148706 TI - Insulin sensitivity index (ISI0, 120) potentially linked to carbon isotopes of breath CO2 for pre-diabetes and type 2 diabetes. AB - New strategies for an accurate and early detection of insulin resistance are important to delay or prevent the acute onset of type 2 diabetes (T2D). Currently, insulin sensitivity index (ISI0,120) is considered to be a viable invasive method of whole-body insulin resistance for use in clinical settings in comparison with other invasive sensitivity indexes like homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). To investigate how these sensitivity indexes link the (13)C/(12)C-carbon isotopes of exhaled breath CO2 to pre-diabetes (PD) and type 2 diabetes in response to glucose ingestion, we studied excretion dynamics of (13)C/(12)C-isotopic fractionations of breath CO2. Here, we show that (13)C/(12)C-isotope ratios of breath CO2 were well correlated with blood glucose, insulin, glycosylated hemoglobin as well as with HOMA-IR and 1/QUICKI. Conversely, the strongest correlation was observed between 1/ISI0,120 and breath CO2 isotopes. Consequently, we determined several optimal diagnostic cut-off points of 1/ISI0,120 and (13)CO2/(12)CO2-isotope ratios to distinctively track the evolution of PD prior to the onset of T2D. Our findings suggest that isotopic breath CO2 is a novel method for accurate estimation of ISI0,120 and thus may open new perspectives into the isotope-specific non-invasive evaluation of insulin resistance for large-scale real-time diabetes screening purposes. PMID- 26148707 TI - The right drugs at the right time for the right patient: the MD Anderson precision oncology decision support platform. AB - The development of resources for clinical interpretation of cancer-associated genetic alterations has significantly lagged behind the technical developments enabling their detection in a time- and cost-efficient manner. The lack of scientific and informatics decision support for oncologists can lead to no action being taken or suboptimal therapeutic choices being made, which could affect the clinical outcome of a patient as well as convoluting research findings from clinical trials. In this article, we describe the precision oncology decision support (PODS) platform developed within The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (IPCT) at MD Anderson Cancer Center; the platform aims to bridge the gap between molecular alteration detection and identification of appropriate treatments. PMID- 26148708 TI - Predicting suicide ideation through intrapersonal and interpersonal factors: The interplay of Big-Five personality traits and social support. AB - While a specific personality trait may escalate suicide ideation, contextual factors such as social support, when provided effectively, may alleviate the effects of such personality traits. This study examined the moderating role of social support in the relationship between the Big-Five personality traits and suicide ideation. Significant interactions were found between social support and extraversion and emotional stability. Specifically, the relationship between emotional stability and extraversion to suicide ideation was exacerbated when social support was low. Slope analysis showed openness also interacted with low social support. Results were computed for frequency, duration and attitude dimensions of suicide ideation. Extraversion interacted with social support to predict all three dimensions. Social support moderated emotional stability to predict frequency and duration, moderated conscientiousness towards frequency and attitude, and moderated openness towards attitude. The results imply that whereas personality traits may be difficult to alter, social support may play a significant role in saving a life. Psychologists should include family and friends when treating a suicidal youth, guiding them to awareness of one's personality and being more supportive. PMID- 26148709 TI - Mortality prediction to hospitalized patients with influenza pneumonia: PO2 /FiO2 combined lymphocyte count is the answer. AB - INTRODUCTION: Community-acquired pneumonia (CAP) severity scores perform well in predicting mortality of CAP patients, but their applicability in influenza pneumonia is powerless. OBJECTIVES: The aim of our research was to test the efficiency of PO2 /FiO2 and CAP severity scores in predicting mortality and intensive care unit (ICU) admission with influenza pneumonia patients. METHODS: We reviewed all patients with positive influenza virus RNA detection in Beijing Chao-Yang Hospital during the 2009-2014 influenza seasons. Outpatients, inpatients with no pneumonia and incomplete data were excluded. We used receiver operating characteristic curves (ROCs) to verify the accuracy of severity scores or indices as mortality predictors in the study patients. RESULTS: Among 170 hospitalized patients with influenza pneumonia, 30 (17.6%) died. Among those who were classified as low-risk (predicted mortality 0.1%-2.1%) by pneumonia severity index (PSI) or confusion, urea, respiratory rate, blood pressure, age >=65 year (CURB-65), the actual mortality ranged from 5.9 to 22.1%. Multivariate logistic regression indicated that hypoxia (PO2 /FiO2 <= 250) and lymphopenia (peripheral blood lymphocyte count <0.8 * 109 /L) were independent risk factors for mortality, with OR value of 22.483 (95% confidence interval 4.927-102.598) and 5.853 (95% confidence interval 1.887-18.152), respectively. PO2 /FiO2 combined lymphocyte count performed well for mortality prediction with area under the curve (AUC) of 0.945, which was significantly better than current CAP severity scores of PSI, CURB-65 and confusion, respiratory rate, blood pressure, age >=65 years for mortality prediction (P < 0.001). The scores or indices for ICU admission prediction to hospitalized patients with influenza pneumonia confirmed a similar pattern and PO2 /FiO2 combined lymphocyte count was also the best predictor for predicting ICU admission. CONCLUSION: In conclusion, we found that PO2 /FiO2 combined lymphocyte count is simple and reliable predictor of hospitalized patients with influenza pneumonia in predicting mortality and ICU admission. When PO2 /FiO2 <= 250 or peripheral blood lymphocyte count <0.8 * 109 /L, the clinician should pay great attention to the possibility of severe influenza pneumonia. PMID- 26148710 TI - Role of the Transporter-Like Sensor Kinase CbrA in Histidine Uptake and Signal Transduction. AB - CbrA is an atypical sensor kinase found in Pseudomonas. The autokinase domain is connected to a putative transporter of the sodium/solute symporter family (SSSF). CbrA functions together with its cognate response regulator, CbrB, and plays an important role in nutrient acquisition, including regulation of hut genes for the utilization of histidine and its derivative, urocanate. Here we report on the findings of a genetic and biochemical analysis of CbrA with a focus on the function of the putative transporter domain. The work was initiated with mutagenesis of histidine uptake-proficient strains to identify histidine-specific transport genes located outside the hut operon. Genes encoding transporters were not identified, but mutations were repeatedly found in cbrA. This, coupled with the findings of [(3)H]histidine transport assays and further mutagenesis, implicated CbrA in histidine uptake. In addition, mutations in different regions of the SSSF domain abolished signal transduction. Site-specific mutations were made at four conserved residues: W55 and G172 (SSSF domain), H766 (H box), and N876 (N box). The mutations W55G, G172H, and N876G compromised histidine transport but had minimal effects on signal transduction. The H766G mutation abolished both transport and signal transduction, but the capacity to transport histidine was restored upon complementation with a transport-defective allele of CbrA, most likely due to interdomain interactions. Our combined data implicate the SSSF domain of CbrA in histidine transport and suggest that transport is coupled to signal transduction. IMPORTANCE: Nutrient acquisition in bacteria typically involves membrane-bound sensors that, via cognate response regulators, determine the activity of specific transporters. However, nutrient perception and uptake are often coupled processes. Thus, from a physiological perspective, it would make sense for systems that couple the process of signaling and transport within a single protein and where transport is itself the stimulus that precipitates signal transduction to have evolved. The CbrA regulator in Pseudomonas represents a unique type of sensor kinase whose autokinase domain is connected to a transporter domain. We present genetic and biochemical evidence that suggests that CbrA plays a dual role in histidine uptake and sensing and that transport is dependent on signal transduction. PMID- 26148711 TI - Ferric Uptake Regulator Fur Control of Putative Iron Acquisition Systems in Clostridium difficile. AB - Clostridium difficile is an anaerobic, Gram-positive, spore-forming opportunistic pathogen and is the most common cause of hospital-acquired infectious diarrhea. Although iron acquisition in the host is a key to survival of bacterial pathogens, high levels of intracellular iron can increase oxidative damage. Therefore, expression of iron acquisition mechanisms is tightly controlled by transcriptional regulators. We identified a C. difficile homologue of the master bacterial iron regulator Fur. Using targetron mutagenesis, we generated a fur insertion mutant of C. difficile. To identify the genes regulated by Fur in C. difficile, we used microarray analysis to compare transcriptional differences between the fur mutant and the wild type when grown in high-iron medium. The fur mutant had increased expression of greater than 70 transcriptional units. Using quantitative reverse transcriptase PCR (qRT-PCR), we analyzed several of the Fur regulated genes identified by the microarray and verified that they are both iron and Fur regulated in C. difficile. Among those Fur- and iron-repressed genes were C. difficile genes encoding 7 putative cation transport systems of different classes. We found that Fur was able to bind the DNA upstream of three Fur repressed genes in electrophoretic mobility shift assays. We also demonstrate that expression of Fur-regulated putative iron acquisition systems was increased during C. difficile infection using the hamster model. Our data suggest that C. difficile expresses multiple iron transport mechanisms in response iron depletion in vitro and in vivo. IMPORTANCE: Clostridium difficile is the most common cause of hospital-acquired infectious diarrhea and has been recently classified as an "urgent" antibiotic resistance threat by the CDC. To survive and cause disease, most bacterial pathogens must acquire the essential enzymatic cofactor iron. While import of adequate iron is essential for most bacterial growth, excess intracellular iron can lead to extensive oxidative damage. Thus, bacteria must regulate iron import to maintain iron homeostasis. We demonstrate here that C. difficile regulates expression of several putative iron acquisition systems using the transcriptional regulator Fur. These import mechanisms are induced under iron limiting conditions in vitro and during C. difficile infection of the host. This suggests that during a C. difficile infection, iron availability is limited in vivo. PMID- 26148712 TI - Gliding Motility of Mycoplasma mobile on Uniform Oligosaccharides. AB - The binding and gliding of Mycoplasma mobile on a plastic plate covered by 53 uniform oligosaccharides were analyzed. Mycoplasmas bound to and glided on only 21 of the fixed sialylated oligosaccharides (SOs), showing that sialic acid is essential as the binding target. The affinities were mostly consistent with our previous results on the inhibitory effects of free SOs and suggested that M. mobile recognizes SOs from the nonreducing end with four continuous sites as follows. (i and ii) A sialic acid at the nonreducing end is tightly recognized by tandemly connected two sites. (iii) The third site is recognized by a loose groove that may be affected by branches. (iv) The fourth site is recognized by a large groove that may be enhanced by branches, especially those with a negative charge. The cells glided on uniform SOs in manners apparently similar to those of the gliding on mixed SOs. The gliding speed was related inversely to the mycoplasma's affinity for SO, suggesting that the detaching step may be one of the speed determinants. The cells glided faster and with smaller fluctuations on the uniform SOs than on the mixtures, suggesting that the drag caused by the variation in SOs influences gliding behaviors. IMPORTANCE: Mycoplasma is a group of bacteria generally parasitic to animals and plants. Some Mycoplasma species form a protrusion at a pole, bind to solid surfaces, and glide in the direction of the protrusion. These procedures are essential for parasitism. Usually, mycoplasmas glide on mixed sialylated oligosaccharides (SOs) derived from glycoprotein and glycolipid. Since gliding motility on uniform oligosaccharides has never been observed, this study gives critical information about recognition and interaction between receptors and SOs. PMID- 26148713 TI - DNA-Binding Protein HU Coordinates Pathogenicity in Vibrio parahaemolyticus. AB - HU is one of the most abundant nucleoid-associated proteins in bacterial cells and regulates the expression of many genes involved in growth, motility, metabolism, and virulence. It is known that Vibrio parahaemolyticus pathogenicity is related to its characteristic rapid growth and that type III secretion system 1 (T3SS1) contributes to its cytotoxicity. However, it is not known if HU plays a role in the pathogenicity of V. parahaemolyticus. In the present study, we investigated the effect of HU proteins HU-2 (HUalpha) (V. parahaemolyticus 2911 [vp2911]) and HUbeta (vp0920) on the pathogenicity of V. parahaemolyticus. We found that a deletion of both HU subunits (yielding the DeltaHUs [Deltavp0920 Deltavp2911] strain), but not single deletions, led to a reduction of the growth rate. In addition, expression levels of T3SS1-related genes, including exsA (positive regulator), exsD (negative regulator), vp1680 (cytotoxic effector), and vp1671 (T3SS1 apparatus), were reduced in the DeltaHUs strain compared to the wild type (WT). As a result, cytotoxicity to HeLa cells was decreased in the DeltaHUs strain. The additional deletion of exsD in the DeltaHUs strain restored T3SS1-related gene expression levels and cytotoxicity but not the growth rate. These results suggest that the HU protein regulates the levels of T3SS1 gene expression and cytotoxicity in a growth rate-independent manner. IMPORTANCE: Nucleoid-binding protein HU regulates cellular behaviors, including nucleoid structuring, general recombination, transposition, growth, replication, motility, metabolism, and virulence. It is thought that both the number of bacteria and the number of virulence factors may affect the pathogenicity of bacteria. In the present study, we investigated which factor(s) has a dominant role during infection in one of the most rapidly growing bacterial species, Vibrio parahaemolyticus. We found that V. parahaemolyticus cytotoxicity is regulated, in a growth rate-independent manner, by the HU proteins through regulation of a number of virulence factors, including T3SS1 gene expression. PMID- 26148714 TI - Energy Conservation Associated with Ethanol Formation from H2 and CO2 in Clostridium autoethanogenum Involving Electron Bifurcation. AB - Most acetogens can reduce CO2 with H2 to acetic acid via the Wood-Ljungdahl pathway, in which the ATP required for formate activation is regenerated in the acetate kinase reaction. However, a few acetogens, such as Clostridium autoethanogenum, Clostridium ljungdahlii, and Clostridium ragsdalei, also form large amounts of ethanol from CO2 and H2. How these anaerobes with a growth pH optimum near 5 conserve energy has remained elusive. We investigated this question by determining the specific activities and cofactor specificities of all relevant oxidoreductases in cell extracts of H2/CO2-grown C. autoethanogenum. The activity studies were backed up by transcriptional and mutational analyses. Most notably, despite the presence of six hydrogenase systems of various types encoded in the genome, the cells appear to contain only one active hydrogenase. The active [FeFe]-hydrogenase is electron bifurcating, with ferredoxin and NADP as the two electron acceptors. Consistently, most of the other active oxidoreductases rely on either reduced ferredoxin and/or NADPH as the electron donor. An exception is ethanol dehydrogenase, which was found to be NAD specific. Methylenetetrahydrofolate reductase activity could only be demonstrated with artificial electron donors. Key to the understanding of this energy metabolism is the presence of membrane-associated reduced ferredoxin:NAD(+) oxidoreductase (Rnf), of electron-bifurcating and ferredoxin-dependent transhydrogenase (Nfn), and of acetaldehyde:ferredoxin oxidoreductase, which is present with very high specific activities in H2/CO2-grown cells. Based on these findings and on thermodynamic considerations, we propose metabolic schemes that allow, depending on the H2 partial pressure, the chemiosmotic synthesis of 0.14 to 1.5 mol ATP per mol ethanol synthesized from CO2 and H2. IMPORTANCE: Ethanol formation from syngas (H2, CO, and CO2) and from H2 and CO2 that is catalyzed by bacteria is presently a much-discussed process for sustainable production of biofuels. Although the process is already in use, its biochemistry is only incompletely understood. The most pertinent question is how the bacteria conserve energy for growth during ethanol formation from H2 and CO2, considering that acetyl coenzyme A (acetyl-CoA), is an intermediate. Can reduction of the activated acetic acid to ethanol with H2 be coupled with the phosphorylation of ADP? Evidence is presented that this is indeed possible, via both substrate-level phosphorylation and electron transport phosphorylation. In the case of substrate-level phosphorylation, acetyl-CoA reduction to ethanol proceeds via free acetic acid involving acetaldehyde:ferredoxin oxidoreductase (carboxylate reductase). PMID- 26148715 TI - Systematic Nomenclature for GGDEF and EAL Domain-Containing Cyclic Di-GMP Turnover Proteins of Escherichia coli. AB - In recent years, Escherichia coli has served as one of a few model bacterial species for studying cyclic di-GMP (c-di-GMP) signaling. The widely used E. coli K-12 laboratory strains possess 29 genes encoding proteins with GGDEF and/or EAL domains, which include 12 diguanylate cyclases (DGC), 13 c-di-GMP-specific phosphodiesterases (PDE), and 4 "degenerate" enzymatically inactive proteins. In addition, six new GGDEF and EAL (GGDEF/EAL) domain-encoding genes, which encode two DGCs and four PDEs, have recently been found in genomic analyses of commensal and pathogenic E. coli strains. As a group of researchers who have been studying the molecular mechanisms and the genomic basis of c-di-GMP signaling in E. coli, we now propose a general and systematic dgc and pde nomenclature for the enzymatically active GGDEF/EAL domain-encoding genes of this model species. This nomenclature is intuitive and easy to memorize, and it can also be applied to additional genes and proteins that might be discovered in various strains of E. coli in future studies. PMID- 26148716 TI - DNA Processing Proteins Involved in the UV-Induced Stress Response of Sulfolobales. AB - The ups operon of Sulfolobus species is highly induced upon UV stress. Previous studies showed that the pili encoded by this operon are involved in cellular aggregation, which is essential for subsequent DNA exchange between cells, resulting in homologous recombination. The presence of this pilus system increases the fitness of Sulfolobus cells under UV light-induced stress conditions, as the transfer of DNA takes place in order to repair UV-induced DNA lesions via homologous recombination. Four conserved genes (saci_1497 to saci_1500) which encode proteins with putative DNA processing functions are present downstream of the ups operon. In this study, we show that after UV treatment the cellular aggregation of strains with saci_1497, saci_1498, and saci_1500 deletions is similar to that of wild-type strains; their survival rates, however, were reduced and similar to or lower than those of the pilus deletion strains, which could not aggregate anymore. DNA recombination assays indicated that saci_1498, encoding a ParB-like protein, plays an important role in DNA transfer. Moreover, biochemical analysis showed that the endonuclease III encoded by saci_1497 nicks UV-damaged DNA. In addition, RecQ-like helicase Saci_1500 is able to unwind homologous recombination intermediates, such as Holliday junctions. Interestingly, a saci_1500 deletion mutant was more sensitive to UV light but not to the replication-stalling agents hydroxyurea and methyl methanesulfonate, suggesting that Saci_1500 functions specifically in the UV damage pathway. Together these results suggest a role of Saci_1497 to Saci_1500 in the repair or transfer of DNA that takes place after UV-induced damage to the genomic DNA of Sulfolobus acidocaldarius. IMPORTANCE: Sulfolobales species increase their fitness after UV stress by a UV-inducible pilus system that enables high rates of DNA exchange between cells. Downstream of the pilus operon, three genes that seem to play a role in the repair or transfer of the DNA between Sulfolobus cells were identified, and their possible functions are discussed. Next to the previously described role of UV-inducible pili in the exchange of DNA, we have thereby increased our knowledge of DNA transfer at the level of DNA processing. This paper therefore contributes to the overall understanding of the DNA exchange mechanism among Sulfolobales cells. PMID- 26148718 TI - Twin classics: research that always inspires/Twin studies: elder twin relationships; Superfecundated twinning in chimpanzees; Conjoined twinning and embryo transfer; Reduced frequency of in vitro multiples/Professional and human interest: first identical twin renal transplant; Identical triplet wedding; Spanakos twins: boxers; Twins in space; Political twins. AB - Ten classic works in twin research are described. These volumes are rich in data, interpretation, and impact, and contain life history material that adds depth and dimension to the quantitative findings. Next, research on social relationships in older twins, superfecundated twinning in chimpanzees; effects of embryo transfer on conjoined twinning and the reduced frequency of in vitro multiples is reviewed. Finally, there has been considerable public interest surrounding the first identical twin renal transplant, an identical triplet wedding; identical twin boxers, a twin living in space, and a politically active twin pair. PMID- 26148717 TI - Phenotypic Suppression of Streptomycin Resistance by Mutations in Multiple Components of the Translation Apparatus. AB - The bacterial ribosome and its associated translation factors are frequent targets of antibiotics, and antibiotic resistance mutations have been found in a number of these components. Such mutations can potentially interact with one another in unpredictable ways, including the phenotypic suppression of one mutation by another. These phenotypic interactions can provide evidence of long range functional interactions throughout the ribosome and its functional complexes and potentially give insights into antibiotic resistance mechanisms. In this study, we used genetics and experimental evolution of the thermophilic bacterium Thermus thermophilus to examine the ability of mutations in various components of the protein synthesis apparatus to suppress the streptomycin resistance phenotypes of mutations in ribosomal protein S12, specifically those located distant from the streptomycin binding site. With genetic selections and strain constructions, we identified suppressor mutations in EF-Tu or in ribosomal protein L11. Using experimental evolution, we identified amino acid substitutions in EF-Tu or in ribosomal proteins S4, S5, L14, or L19, some of which were found to also relieve streptomycin resistance. The wide dispersal of these mutations is consistent with long-range functional interactions among components of the translational machinery and indicates that streptomycin resistance can result from the modulation of long-range conformational signals. IMPORTANCE: The thermophilic bacterium Thermus thermophilus has become a model system for high resolution structural studies of macromolecular complexes, such as the ribosome, while its natural competence for transformation facilitates genetic approaches. Genetic studies of T. thermophilus ribosomes can take advantage of existing high resolution crystallographic information to allow a structural interpretation of phenotypic interactions among mutations. Using a combination of genetic selections, strain constructions, and experimental evolution, we find that certain mutations in the translation apparatus can suppress the phenotype of certain antibiotic resistance mutations. Suppression of resistance can occur by mutations located distant in the ribosome or in a translation factor. These observations suggest the existence of long-range conformational signals in the translating ribosome, particularly during the decoding of mRNA. PMID- 26148719 TI - Are regulatory strategies necessary in the regulation of accuracy? The effect of direct-access answers. AB - Previous studies have shown that, when people asked to retrieve something from memory have the chance to regulate memory accuracy, the accuracy of their final report increases. Such regulation of accuracy can be made through one of several strategies: the report option, the grain-size option, or the plurality option. However, sometimes an answer can be directly accessed and reported without resorting to such strategies. The direct-access answers are expected to be fast, have high accuracy, and be rated with high probabilities of being correct. Thus, direct-access answers alone could explain the increase of accuracy that has been considered the outcome of regulatory strategies. If so, regulatory strategies may not be needed to explain the previous results. In two experiments, we disentangled the effects of direct-access answers and regulatory strategies in the increase of accuracy. We identified a subset of direct-access answers, and then examined the regulation of accuracy with the plurality option when they were removed. Participants answered questions with six (Exp. 1) or five (Exp. 2) alternatives. Their task was, first, to select as many alternatives as they wanted and, second, to select only two or four alternatives. The results showed that the direct-access answer affected the regulation of accuracy and made it easier. However, the results also showed that regulatory strategies, in this case the plurality option, are needed to explain why the accuracy of final report increases after successful regulation. This research highlighted the relevance of taking direct-access answers into account in the study of the regulation of accuracy. PMID- 26148720 TI - Additional evidence for a dual-strategy model of reasoning: Probabilistic reasoning is more invariant than reasoning about logical validity. AB - One of the major debates concerning the nature of inferential reasoning is between counterexample-based strategies such as mental model theory and the statistical strategies underlying probabilistic models. The dual-strategy model proposed by Verschueren, Schaeken, and d'Ydewalle (2005a, 2005b) suggests that people might have access to both kinds of strategies. One of the postulates of this approach is that statistical strategies correspond to low-cost, intuitive modes of evaluation, whereas counterexample strategies are higher-cost and more variable in use. We examined this hypothesis by using a deductive-updating paradigm. The results of Study 1 showed that individual differences in strategy use predict different levels of deductive updating on inferences about logical validity. Study 2 demonstrated no such variation when explicitly probabilistic inferences were examined. Study 3 showed that presenting updating problems with probabilistic inferences modified performance on subsequent problems using logical validity, whereas the opposite was not true. These results provide clear evidence that the processes used to make probabilistic inferences are less subject to variation than those used to make inferences of logical validity. PMID- 26148721 TI - A splicing mutation in the DMD gene detected by next-generation sequencing and confirmed by mRNA and protein analysis. AB - BACKGROUND: Dystrophinopathies, either the severe Duchenne Muscular Dystrophy (DMD) or the milder Becker Muscular Dystrophy (BMD), are X-linked recessive disorders caused by mutations in the DMD gene. DMD is one of the longest human genes. Large deletions or duplications account for 60-80% of the mutations. Remaining anomalies consist in point mutations or small rearrangements. Routinely, the molecular diagnosis is done by a Multiplex Ligation-dependent Probe Amplification (MLPA) or array Comparative Genome Hybridization (aCGH), followed, if negative, by Sanger sequencing of all exons. METHODS: In this study, massive parallel sequencing (MPS) or next generation sequencing (NGS) was used to make a rapid and costless molecular diagnosis in a young boy suspected of DMD. RESULTS: A small deletion: NM_004006.2:c.2803+5_2803+8del was identified. The diagnosis was performed in one single manipulation and within a week. The consequence of this intronic mutation is a skipping of exon 21 confirmed by mRNA and protein analysis. CONCLUSIONS: NGS appears to be an efficient new strategy in DMD molecular diagnosis. It highlights the major evolution of the diagnostic strategy towards high throughput technologies, where bioinformatics analysis becomes the real challenge for variations detection. This is the first study reporting in vivo impact of this intronic mutation. PMID- 26148722 TI - Hypermethylation in gastric cancer. AB - Although gastric cancer (GC) is highly prevalent in China and is a leading cause of cancer-related death, major advances in early diagnostic and effective therapeutic strategies have not been made. GC patients are usually diagnosed at an advanced stage and the prognosis is still poor. Over the years, many efforts have been done on exploring the pathology of GC. In particular, genome-wide analysis tools have been widely used in the detection of genetic and epigenetic alterations in GC. For example, many tumor suppressor genes have been found to be aberrantly hypermethylated in GCs, and some even in gastric precancerous lesions, suggesting a role of this molecular event in early gastric tumorigenesis. In addition, accumulating evidences have demonstrated that some hypermethylated genes can be used as potential biomarkers for detection and diagnosis of GC in biopsy specimens and non-invasive body fluids. These exciting advances provide unprecedented opportunities for the development of molecular-based novel diagnostic, prognostic, and therapeutic strategies for GC. Here, we reviewed recent findings on the promoter hypermethylation of tumor suppressor genes in GC and aimed to provide better understanding of the contribution of this epigenetic event to gastric tumorigenesis. PMID- 26148723 TI - Development of a rapid and sensitive one-step reverse transcription-nested polymerase chain reaction in a single tube using the droplet-polymerase chain reaction machine. AB - BACKGROUND: Reverse transcription (RT)-nested polymerase chain reaction (PCR) is a time-consuming procedure because it has several handling steps and is associated with the risk of cross-contamination during each step. Therefore, a rapid and sensitive one-step RT-nested PCR was developed that could be performed in a single tube using a droplet-PCR machine. METHODS: The K562 BCR-ABL mRNA positive cell line as well as bone marrow aspirates from 5 patients with chronic myelogenous leukemia (CML) and 5 controls without CML were used. We evaluated one step RT-nested PCR using the droplet-PCR machine. RESULTS: One-step RT-nested PCR performed in a single tube using the droplet-PCR machine enabled the detection of BCR-ABL mRNA within 40min, which was 10(3)-fold superior to conventional RT nested PCR using three steps in separate tubes. The sensitivity of the one-step RT-nested PCR was 0.001%, with sample reactivity comparable to that of the conventional assay. CONCLUSIONS: One-step RT-nested PCR was developed using the droplet-PCR machine, which enabled all reactions to be performed in a single tube accurately and rapidly and with high sensitivity. This one-step RT-nested PCR may be applicable to a wide spectrum of genetic tests in clinical laboratories. PMID- 26148724 TI - 60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies. AB - A pulsatile pattern of secretion is a characteristic of many hormonal systems, including the glucocorticoid-producing hypothalamic-pituitary-adrenal (HPA) axis. Despite recent evidence supporting its importance for behavioral, neuroendocrine and transcriptional effects of glucocorticoids, there has been a paucity of information regarding the origin of glucocorticoid pulsatility. In this review we discuss the mechanisms regulating pulsatile dynamics of the HPA axis, and how these dynamics become disrupted in disease. Our recent mathematical, experimental and clinical studies show that glucocorticoid pulsatility can be generated and maintained by dynamic processes at the level of the pituitary-adrenal axis, and that an intra-adrenal negative feedback may contribute to these dynamics. PMID- 26148726 TI - Implementation of a cross-border health service: physician and pharmacists' opinions from the epSOS project. AB - OBJECTIVES: To explore the opinions of health professionals with experience of the European Patient Smart Open Services (epSOS) system regarding the epSOS services perceived utility, potential impact and main barriers and facilitators to its use. METHODS: Qualitative study design involving focus groups with health care professionals with experience of epSOS system. A semi-structured topic guide was developed to guide the discussion. RESULTS: epSOS services were seen as interesting intuitive services and easy to operate. The greatest impact was in terms of positive impact on communication, clinical safety and patient management. Data reliability, difficulties in accessing the service and aspects related to information technology architecture were considered the most relevant barriers. CONCLUSION: This study has provided insights into the strengths and limitations of two new eHealth services for use across countries within the European Union, and has provided indications of how those services could be improved. PMID- 26148725 TI - FGF23 gene regulation by 1,25-dihydroxyvitamin D: opposing effects in adipocytes and osteocytes. AB - In a closed endocrine loop, 1,25-dihydroxyvitamin D3 (1,25D) induces the expression of fibroblast growth factor 23 (FGF23) in bone, with the phosphaturic peptide in turn acting at kidney to feedback repress CYP27B1 and induce CYP24A1 to limit the levels of 1,25D. In 3T3-L1 differentiated adipocytes, 1,25D represses FGF23 and leptin expression and induces C/EBPbeta, but does not affect leptin receptor transcription. Conversely, in UMR-106 osteoblast-like cells, FGF23 mRNA concentrations are upregulated by 1,25D, an effect that is blunted by lysophosphatidic acid, a cell-surface acting ligand. Progressive truncation of the mouse FGF23 proximal promoter linked in luciferase reporter constructs reveals a 1,25D-responsive region between -400 and -200 bp. A 0.6 kb fragment of the mouse FGF23 promoter, linked in a reporter construct, responds to 1,25D with a fourfold enhancement of transcription in transfected K562 cells. Mutation of either an ETS1 site at -346 bp, or an adjacent candidate vitamin D receptor (VDR)/Nurr1-element, in the 0.6 kb reporter construct reduces the transcriptional activity elicited by 1,25D to a level that is not significantly different from a minimal promoter. This composite ETS1-VDR/Nurr1 cis-element may function as a switch between induction (osteocytes) and repression (adipocytes) of FGF23, depending on the cellular setting of transcription factors. Moreover, experiments demonstrate that a 1 kb mouse FGF23 promoter-reporter construct, transfected into MC3T3-E1 osteoblast-like cells, responds to a high calcium challenge with a statistically significant 1.7- to 2.0-fold enhancement of transcription. Thus, the FGF23 proximal promoter harbors cis elements that drive responsiveness to 1,25D and calcium, agents that induce FGF23 to curtail the pathologic consequences of their excess. PMID- 26148727 TI - 'Patient activation' as an outcome measure for primary care? PMID- 26148728 TI - Editorial: Dielectrophoresis 2015. PMID- 26148736 TI - Gut feelings 1. Mind, mood and gut in irritable bowel syndrome: approaches to psychiatric care. AB - OBJECTIVE: Psychiatrists are likely to encounter patients with irritable bowel syndrome (IBS). We aim to provide a clinically-focused summary of psychiatric comorbidities and management. CONCLUSIONS: IBS affects up to 15% of the population. Antidepressants and brief psychotherapy can reduce symptom severity and improve coping. These treatments are effective for patients without comorbid mental illness, as well as those with increased somatisation, health-care seeking and sexual abuse histories. PMID- 26148737 TI - Recovery-based services in a psychiatric intensive care unit - the consumer perspective. AB - OBJECTIVE: To describe the implementation of recovery-based practice into a psychiatric intensive care unit, and report change in seclusion rates over the period when these changes were introduced (2011-2013). METHOD: Recovery-based practices including collaborative care, safety care plans, a comfort room, and debriefing after coercive interventions were introduced. A carer consultant was employed. A restraint and seclusion review committee, chaired by a peer worker, was established. A consumer exit interview was introduced and these data were collected, reviewed by staff and the peer worker and used to improve the ward environment. Rates of seclusion were measured during the period when recovery based practices were introduced. RESULTS: Consumer feedback indicated that positive aspects of the psychiatric intensive care unit included approachable, helpful staff and completion of a safety care plan. Negative aspects included lack of involvement in decisions about admission and about medications, the non smoking policy, and being placed in seclusion or restraint. There was a significant reduction in the number of consumers secluded and the total number of seclusions. CONCLUSIONS: Recovery principles can be successfully introduced in a psychiatric intensive care unit environment. Introduction of recovery based practice was associated with a reduction in seclusion. PMID- 26148738 TI - 'Teaching' the therapeutic alliance Part 2. Treating patients, supporting trainees: towards a broader view of psychotherapy training. AB - OBJECTIVE: This is the second of two papers focusing on the need for a broader view of contemporary psychotherapy training. CONCLUSION: Some preliminary suggestions for affective or "right-brain" training, including supervision for psychotherapy with patients with developmental trauma and Balint-style groups are made. PMID- 26148739 TI - Pathologic Factors Associated with Prognosis after Adjuvant Chemotherapy in Stage II/III Microsatellite-Unstable Colorectal Cancers. AB - BACKGROUND: Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet. METHODS: A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy. We statistically analyzed the associations of these factors with disease-free survival (DFS). RESULTS: Using a Kaplan- Meier analysis with log rank test, we determined that ulceroinfiltrative gross type (p=.003), pT4 (p<.001), pN2 (p=.002), perineural invasion (p=.001), absence of peritumoral lymphoid reaction (p=.041), signet ring cell component (p=.006), and cribriform comedo component (p=.004) were significantly associated with worse DFS in patients receiving oxaliplatin-based adjuvant chemotherapy (n=45). By contrast, pT4 (p<.001) and tumor budding-positivity (p=.032) were significant predictors of poor survival in patients receiving non-oxaliplatin-based adjuvant chemotherapy (n=80). In Cox proportional hazards regression model-based univariate and multivariate analyses, pT category (pT1-3 vs pT4) was the only significant prognostic factor in patients receiving non-oxaliplatin-based adjuvant chemotherapy, whereas pT category, signet ring cell histology and cribriform comedo histology remained independent prognostic factors in patients receiving oxaliplatin-based adjuvant chemotherapy. CONCLUSIONS: pT4 status is the most significant pathologic determinant of poor outcome after fluoropyrimidine-based adjuvant chemotherapy in patients with stage II/III MSI-H CRC. PMID- 26148740 TI - Accuracy of Core Needle Biopsy Versus Fine Needle Aspiration Cytology for Diagnosing Salivary Gland Tumors. AB - BACKGROUND: Core needle biopsy is a relatively new technique used to diagnose salivary gland lesions, and its role in comparison with fine needle aspiration cytology needs to be refined. METHODS: We compared the results of 228 ultrasound guided core needle biopsy and 371 fine needle aspiration procedures performed on major salivary gland tumors with their postoperative histological diagnoses. RESULTS: Core needle biopsy resulted in significantly higher sensitivity and more accurate tumor subtyping, especially for malignant tumors, than fine needle aspiration. No patient developed major complications after core needle biopsy. CONCLUSIONS: We recommend ultrasoundguided core needle biopsy as the primary diagnostic tool for the preoperative evaluation of patients with salivary gland lesions, especially when malignancy is suspected. PMID- 26148741 TI - Serous Cystadenoma and Fibrothecoma: A Rare Combination in Collision Tumor of Ovary with Pseudo-Meigs Syndrome. PMID- 26148742 TI - Perfluoroalkyl acids and time to pregnancy revisited: An update from the Danish National Birth Cohort. AB - BACKGROUND: We previously demonstrated an association between plasma perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and longer time to pregnancy (TTP) in a sample from the Danish National Birth Cohort (DNBC, 1996 2002). In this study we investigated this association in a new sample from the same cohort. METHODS: Sample 1 consisted of 440 women, and Sample 2 consisted of 1161 women from whom we previously published the associations between PFOS or PFOA and TTP. We performed sample-specific and pooled analyses using discrete time survival analyses to estimate fecundability ratios according to PFOS and PFOA quartiles, adjusted for potential confounders chosen guided by a directed acyclic graph. We also estimated odds ratios for infertility (TTP > 12 months or infertility treatment) according to PFOS and PFOA by multivariable logistic regression. RESULTS: In Sample 1 PFOS was not associated with lower fecundability ratios or infertility, and there was a tendency towards longer TTP with increasing PFOA only in parous women. In Sample 2 previously reported associations were again seen. In the pooled analyses including both parous and nulliparous women fecundability ratios were 13-22 % lower for the three higher quartiles of PFOS or PFOA compared to the reference quartile. CONCLUSIONS: The pooled analyses were driven by the larger old sample, but we did not corroborate our previous finding of an association between high PFOS and longer TTP in the new sample. The tendency towards an association for PFOA and TTP in parous women may be due to reverse causation. Results from the new sample are more in line with the recent literature. PMID- 26148743 TI - Effects of increasing levels of pharmaceutical penicillin G contamination on structure of free living nematode communities in experimental microcosms. AB - A microcosm experiment was conducted to examine the effects of the pharmaceutical (penicillin G) on free living nematode communities of a Tunisian coastal zone (South-Western Mediterranean Sea). Sediments were contaminated with five penicillin G dose [D1 (3 mgL(-1)), D2 (30 mgL(-1)), D3 (300 mgL(-1)), D4 (600 mgL(-1)), D5 (700 mgL(-1))], and effects were examined after 30 days. Results showed significant differences between nematode assemblages from undisturbed controls and those from penicillin G treatments. Most univariate measures, including diversity (H'), species richness (d), equitability (J) and number of species (S) decreased significantly with increasing level of the antibiotic contamination. Results from multivariate analyses of the species abundance data demonstrated that responses of nematode species to the penicillin treatments were varied: Kraspedonema octogoniata and Paracomesoma dubium were eliminated at all the antibiotic doses tested and seemed to be intolerant species to penicillin G contamination; Oncholaimus campylocercoides although survived even the highest dose D5, showed definite reduction in its abundance and may be classified as "opportunistic" species at this dose, whereas, Nannolaimoides decoratus which showed a positive response with an increase in density even at highest concentration of contaminant, seems to be "penicillin G resistant" species. PMID- 26148744 TI - DINGO: differential network analysis in genomics. AB - MOTIVATION: Cancer progression and development are initiated by aberrations in various molecular networks through coordinated changes across multiple genes and pathways. It is important to understand how these networks change under different stress conditions and/or patient-specific groups to infer differential patterns of activation and inhibition. Existing methods are limited to correlation networks that are independently estimated from separate group-specific data and without due consideration of relationships that are conserved across multiple groups. METHOD: We propose a pathway-based differential network analysis in genomics (DINGO) model for estimating group-specific networks and making inference on the differential networks. DINGO jointly estimates the group specific conditional dependencies by decomposing them into global and group specific components. The delineation of these components allows for a more refined picture of the major driver and passenger events in the elucidation of cancer progression and development. RESULTS: Simulation studies demonstrate that DINGO provides more accurate group-specific conditional dependencies than achieved by using separate estimation approaches. We apply DINGO to key signaling pathways in glioblastoma to build differential networks for long-term survivors and short-term survivors in The Cancer Genome Atlas. The hub genes found by mRNA expression, DNA copy number, methylation and microRNA expression reveal several important roles in glioblastoma progression. AVAILABILITY AND IMPLEMENTATION: R Package at: odin.mdacc.tmc.edu/~vbaladan. CONTACT: veera@mdanderson.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26148745 TI - Clinical assessment and health-related quality of life in patients with non cardiac chest pain. AB - INTRODUCTION: Non-cardiac chest pain (NCCP) is mainly related to oesophageal disease, and in spite of being a common condition in Mexico, information regarding it is scarce. AIM: To assess the clinical characteristics and health related quality of life of patients with NCCP of presumed oesophageal origin. MATERIAL AND METHODS: Patients with NCCP of presumed oesophageal origin with no previous treatment were included in the study. Associated symptoms were assessed and upper gastrointestinal endoscopy and 24-hour oesophageal pH monitoring were performed to diagnose gastroesophageal reflux disease, while oesophageal manometry was used to determine oesophageal motility disorders. The SF-36 Health Related Quality of Life (HR-QoL) questionnaire was completed and its results compared to a control group without oesophageal symptoms. RESULTS: The study included 33 patients, of which 61% were women, and the mean age was 46.1 (+/ 11.6) years. Causes of NCCP were gastroesophageal reflux disease in 48%, achalasia in 34%, and functional chest pain in 18%. The average progression time for chest pain was 24 (2-240) months, with <= 3 events/week in 52% of the patients. The most frequent accompanying symptoms were: regurgitation (81%), dysphagia (72%) and heartburn (66%). Patients with NCCP show deterioration in HR QoL compared to the control group (P=.01), regardless of chest pain aetiology. The most affected areas were general perception of health, emotional issues, and mental health sub-scale (P>0.05). CONCLUSIONS: In our population, patients with NCCP show deterioration in HR-QoL regardless of the aetiology, frequency, and accompanying symptoms. PMID- 26148746 TI - Local cutaneous nerve terminal and mast cell responses to manual acupuncture in acupoint LI4 area of the rats. AB - Previous studies have shown that the effects of manual acupuncture (MA) are contributed by collagen fibers and mast cells in local acupoints, at which acupuncture stimulation causes various afferent fiber groups to be excited. However what happens in local nerve fibers and mast cells after MA remains unclear. The aim of this study was to examine the response of cutaneous nerve fibers and mast cells to MA stimulation in acupoint Hegu (LI4). The contralateral LI4 of the same rat was used as a non-stimulated control. Immnohistochemistry analysis were carried out to observe the expression of histamine (HA), serotonin (5-HT) and nociceptive neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), in the LI4 area. Mast cells were labeled with anti-mast cell tryptase antibody and simultaneously with HA or 5-HT primary antibodies to observe their co-expression. Our results showed that SP and CGRP were expressed more highly on the cutaneous nerve fibers of LI4 after MA stimulation than that of the control. Mast cells aggregated in close proximity to the blood vessels in intra-epidermis and dermis and some of them with degranulation in the lower dermis and subcutaneous tissue of LI4. Both mast cells and their granules appeared with HA (+) and 5-HT (+) expression at stimulated L14 sites, while a few intact mast cells with a little expression of 5-HT and HA were distributed in areas of non-stimulated L14. The results indicated that local cutaneous nerve terminals and mast cells responded to MA with higher expression of SP and CGRP in nerve fibers, as well as with aggregation and degranulation of mast cells with HA and 5-HT granules at acupoint LI4. These neuroactive substances may convey signals to certain pathways that contribute to the effects of acupuncture. PMID- 26148748 TI - ? PMID- 26148749 TI - Lectins as probes for assessing the accessibility of N-linked glycans in relation to the conformational changes of fibronectin. AB - Fibronectin, a ~ 450-kDa protein with 4-9% (w/w) glycosylation, is a key component of extracellular matrices and has a high conformational lability regarding its functions. However, the accessibility and the role of glycosylated moieties associated with the conformational changes of fibronectin are poorly understood. Using lectins as probes, we developed an approach comprising dynamic light scattering, turbidimetry measurements, and isothermal titration calorimetry to assess the accessibility of glycosylated moieties of fibronectin undergoing thermal-induced conformational changes. Among a set of 14 lectins, fibronectin mainly reacted with mannose-binding lectins, specifically concanavalin A. When temperature was raised from 25 to 50 degrees C, fibronectin underwent progressive unfolding, but the conformation of concanavalin A was unaffected. Dynamic light scattering, turbidimetry measurements, and isothermal titration calorimetry showed increased concanavalin A binding to fibronectin during progressive thermal-induced unfolding of the protein core. Such data suggest that mannosylated residues are progressively exposed as fibronectin unfolds. Because oligosaccharide moieties can be differently exposed to cells, and the cell's responses could be modified physiologically or pathologically, modulation of fibronectin sugar chains could be relevant to its biological functions. Thus, lectins might be useful tools to probe the glycosylation accessibility accompanying changes in protein core folding, for which a better understanding would be of value for biological and biomedical research. PMID- 26148750 TI - A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer. AB - PURPOSE: Icotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. A phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with whole-brain radiotherapy (WBRT) in Chinese NSCLC patients with brain metastases (BMs); the cerebrospinal fluid (CSF)/plasma concentrations of icotinib were also investigated. METHODS: Eligible patients had BMs from NSCLC, regardless of the EGFR status. Icotinib was administered at 125 mg orally 3 times/day until tumor progression or unacceptable toxicity, concurrently with WBRT (3.0 Gy per day, 5 days per week, to 30 Gy). CSF and plasma samples were collected simultaneously from 10 patients. Icotinib concentrations in the CSF and plasma were measured by high-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Twenty patients were enrolled. The median follow-up time was 20.0 months. The overall response rate was 80.0%. The median progression-free survival time was 7.0 months (95% CI 1.2-13.2 months), and the median survival time (MST) was 14.6 months (95% CI 12.5 16.7 months). Of the 18 patients with known EGFR status, the MST was 22.0 months for those with an EGFR mutation and was 7.5 months for those with wild-type EGFR (P = 0.0001). The CSF concentration and penetration rate of icotinib were 11.6 +/ 9.1 ng/mL and 1.4 +/- 1.1%, respectively. No patient experienced >=grade 4 toxicity. CONCLUSIONS: Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from NSCLC. This clinical benefit was related to the presence of activating EGFR mutations. PMID- 26148747 TI - Positive allosteric modulators of metabotropic glutamate 2 receptors in schizophrenia treatment. AB - The past two decades have witnessed a rise in the 'NMDA receptor hypofunction' hypothesis for schizophrenia, a devastating disorder that affects around 1% of the population worldwide. A variety of presynaptic, postsynaptic, and regulatory proteins involved in glutamatergic signaling have thus been proposed as potential therapeutic targets. This review focuses on positive allosteric modulation of metabotropic glutamate 2 receptors (mGlu2Rs) and discusses how recent preclinical epigenetic data may provide a molecular explanation for the discrepant results of clinical studies, further stimulating the field to exploit the promise of mGlu2R as a target for schizophrenia treatment. PMID- 26148751 TI - Predictability Bounds of Electronic Health Records. AB - The ability to intervene in disease progression given a person's disease history has the potential to solve one of society's most pressing issues: advancing health care delivery and reducing its cost. Controlling disease progression is inherently associated with the ability to predict possible future diseases given a patient's medical history. We invoke an information-theoretic methodology to quantify the level of predictability inherent in disease histories of a large electronic health records dataset with over half a million patients. In our analysis, we progress from zeroth order through temporal informed statistics, both from an individual patient's standpoint and also considering the collective effects. Our findings confirm our intuition that knowledge of common disease progressions results in higher predictability bounds than treating disease histories independently. We complement this result by showing the point at which the temporal dependence structure vanishes with increasing orders of the time correlated statistic. Surprisingly, we also show that shuffling individual disease histories only marginally degrades the predictability bounds. This apparent contradiction with respect to the importance of time-ordered information is indicative of the complexities involved in capturing the health-care process and the difficulties associated with utilising this information in universal prediction algorithms. PMID- 26148752 TI - Giant Herpes Labialis in a Child with DOCK8-deficient Hyper-IgE Syndrome. PMID- 26148754 TI - Agnes Fouet - departing Editor-in-Chief. PMID- 26148753 TI - Golden ratio sparse MRI using tiny golden angles. AB - PURPOSE: The combination of fully balanced SSFP sequences with iterative golden angle radial sparse parallel (iGRASP) MRI leads to strong image artifacts due to eddy currents caused by the large angular increment of the golden angle ordering. The purpose of this work is to enable the combination of iterative golden angle radial sparse parallel MRI with balanced SSFP using the recently presented tiny golden angles. METHODS: The tiny golden angle trajectories are analyzed for their incoherence properties in relation to sparse imaging using the time-resolved point-spread functions. Tiny golden angle radial sparse parallel (tyGRASP) MRI is introduced and evaluated with applications in cardiac imaging and dynamic imaging of the temporomandibular joint. The results are analyzed in detail for 3 T and verified for 1.5 T. RESULTS: The incoherence properties of the tiny golden angle trajectory are comparable to the incoherence properties of the golden angle trajectory and are well suited for sparse MRI reconstruction. The proposed tiny golden angle radial sparse parallel MRI method strongly reduces eddy current related artifacts for both applications. CONCLUSION: This work enables sparse, golden-ratio-based imaging with balanced SSFP sequences. Magn Reson Med 75:2372 2378, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26148755 TI - Pancreaticoduodenectomy with Reconstruction of the Mesentericoportal Vein by the Parietal Peritoneum: 'Safi Dokmak Vascular Graft'. AB - BACKGROUND: Venous resections are frequent during hepatopancreatobiliary (HPB) surgery and a rapidly available graft may be needed, especially if it had not been planned preoperatively.1 (-) 3 Our group recently reported results on the use of the parietal peritoneum (PP) as an autologous substitute graft (ASG) for reconstruction of the mesentericoportal vein (MPV) in 30 patients for the first time.4 METHODS: Between December 2010 and January 2015, a total of 52 patients underwent HPB surgery with venous resection/reconstruction with the PP. The PP was harvested rapidly through the same surgical incision in the same surgical field, and reconstruction was generally performed after the specimen was removed. The ASG was harvested from the PP of the diaphragm (n = 22), the hypochondrium (n = 19), the falciform ligament (n = 6) and the prerenal area (n = 5), and used as a lateral (n = 49) or tubular (n = 3) graft. The presence of peritoneal carcinomatosis was a contraindication. Postoperative anticoagulation was standard and venous patency was assessed by routine computed tomography (CT) scan in all patients. All data were collected prospectively and complications were recorded according to the Clavien-Dindo classification.5 Our experience is illustrated in a patient who underwent pancreaticoduodenectomy with reconstruction of the MPV, using the PP, for recurrent pancreatic adenocarcinoma on an intraductal papillary mucinous neoplasia, and who was treated 5 years ago by distal pancreatectomy. RESULTS: Overall, 32 men and 20 women, mean age 60 years (range 31-83), underwent resection of the pancreas (n = 29), the liver (n = 22), or both (n = 1). Mean size of the ASG was 23 mm (range 10-80), and it was used for reconstruction of the MPV (n = 42), the hepatic veins (n = 5), or the vena cava (n = 5) for malignant disease (98 %). Emergency reconstruction was necessary in six patients due to prolonged vascular occlusion. One non-related mortality was observed (2 %) as a result of septic complications after right hepatectomy. Eight (15 %) complications were greater than grade III of the Clavien-Dindo classification, but there were no PP-related or hemorrhagic complications. Mean hospital stay was 16 days (range 6-48). After a mean follow-up of 11 months (range 1-46), the overall patency rate was 96, 100 % for the lateral graft, and 33 % for the tubular graft. CONCLUSIONS: The Safi Dokmak vascular graft using the PP for lateral reconstruction of the MPV may be harvested rapidly with no limitation in size, can be temporarily used, and is inexpensive and safe. Finally, therapeutic anticoagulation is not needed and the theoretical risk of infection is very low. PMID- 26148756 TI - Collaborations between SSO and the Connective Tissue Oncology Society (CTOS) series. PMID- 26148757 TI - Multivisceral Resection for Gastric Cancer: Results from the US Gastric Cancer Collaborative. AB - BACKGROUND: Resection of an adjacent organ during gastrectomy for gastric cancer is occasionally necessary to achieve margin clearance. The short- and long-term outcomes of this approach remain unclear. METHODS: Patients who underwent gastric cancer resection in seven U.S. academic institutions from 2000 to 2012 were evaluated to compare perioperative morbidity, mortality, and survival outcomes, stratified by the need for and type of multivisceral resection (MVR). RESULTS: Of 835 patients undergoing curative-intent gastrectomy, 159 (19 %) had MVR. The most common adjacent organs resected were the spleen (48 %), pancreas (27 %), liver segments 2/3 (14 %), and colon (13 %). As extent of resection increased (gastrectomy only, n = 676; MVR without pancreatectomy, n = 116; and MVR with pancreatectomy, n = 43), perioperative morbidity was higher: any complication (45, 60, 59 %, p = 0.012), major complication (17, 31, 33 %, p = 0.001), anastomotic leak (5, 11, 19 %, p < 0.001), and respiratory failure (9, 15, 22 %, p = 0.012). However, perioperative mortality did not significantly increase (30 day: 3, 4, 2 %, p = 0.74; 90-day: 6, 8, 9 %, p = 0.61). Overall survival after resection decreased as extent of resection increased (5-year: 42, 28, 6 %). After controlling for age, race, T stage, N stage, grade, margin status, perineural invasion, adjuvant therapy, and blood transfusion, MVR with pancreatectomy (HR 1.67, p = 0.044), but not MVR without pancreatectomy (HR 0.97, p = 0.759), remained an independent predictor of poor survival. CONCLUSION: In this modern, multi-institutional cohort of gastric cancer patients, multivisceral resection was associated with higher perioperative morbidity but not significantly higher perioperative mortality. If concomitant pancreatectomy is anticipated, patients should be selected with extreme caution because long-term survival remains poor. PMID- 26148758 TI - Treatment-Related Mortality After Cytoreductive Surgery and HIPEC in Patients with Colorectal Peritoneal Carcinomatosis is Underestimated by Conventional Parameters. AB - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as treatment for patients with colorectal peritoneal carcinomatosis (PC) is regarded as an extensive procedure. The risk of postoperative mortality after major abdominal surgery might be substantially higher than described by the 30-day mortality. This study aims to identify causes of 1-year mortality, thereby assessing a more accurate treatment-related mortality rate after CRS + HIPEC. METHODS: All subsequent patients with colorectal PC treated with CRS + HIPEC with complete macroscopic cytoreduction in two tertiary hospitals between April 2005 and April 2013 were included in this study. Causes of 1-year mortality were carefully analyzed and patient data were compared between patients who died or did not die within 12 months after CRS + HIPEC. RESULTS: Of the 245 included patients, 34 (13.9 %) died within 12 months after CRS + HIPEC. The overall treatment-related mortality rate was 4.9 % (n = 12), and the 30-day and in-hospital mortality rates were 1.6 % (n = 4) and 2.4 % (n = 6), respectively. Furthermore, 18 patients (7.3 %) died due to early recurrent disease. Three patients (1.2 %) died of cardiovascular events, unrelated to CRS + HIPEC. The 1-year mortality group had more extensive peritoneal disease (p = 0.02) and the operative time in this group was longer (p < 0.001). CONCLUSIONS: Overall treatment-related mortality was considerably higher than described by the 30-day and in-hospital mortality rate. However, even though complete macroscopic cytoreduction was achieved in every patient, the main cause of 1-year mortality was early recurrent disease. Both findings are valuable in preoperative patient selection, as well as in preoperative counseling of patients undergoing a CRS + HIPEC procedure. PMID- 26148759 TI - Survival from Differentiated Thyroid Cancer: What Has Age Got to Do with It? AB - BACKGROUND: In most staging systems, 45 years of age is used to differentiate low risk thyroid cancer from high risk thyroid cancer. However, recent studies have questioned both the precise 45 year age point and the concept of using a binary cut off as accurate predictors of disease specific mortality. METHODS: A cohort of 3664 thyroid cancer patients that received surgery and adjuvant treatment at Memorial Sloan Kettering Cancer Center (MSKCC) from the years 1985 to 2010 were analyzed to determine the significance of age at diagnosis as a categorical variable at a variety of age cutoffs (5 year intervals between 30 and 70 years of age). The unadjusted and adjusted hazard ratio for the association between disease-specific survival and age was determined using a Cox proportional hazards model adjusted for other predictive variables sex, histology, and pathological T, N, and M status. Furthermore, predictive nomograms of disease-specific mortality were created and validated on an external dataset of 4551 patients to evaluate the impact of age at diagnosis as both a categorical and continuous variable. RESULTS: In the MSKCC cohort, with a median follow-up time of 54 months (range 1 332), there were 59 deaths from thyroid cancer with a 10 year disease-specific survival of 96%. Adjusted hazard ratios for all age cutoffs from age 30 to age 70 years were significant. There was no specific cutoff age which risk stratifies patients with differentiated thyroid cancer (DTC). Categorizing age into five strata (<40, 40-49, 50-59, 60-69 and >70 years) showed a 37-fold increase in hazard ratio from age <40 years to age >70 years. A predictive nomogram using age as a continuous variable with other predictive variables had a high concordance index of 96%. Validation on the external cohort had a concordance index of 73%. CONCLUSIONS: Mortality from DTC increases progressively with advancing age. There is no specific cutoff age which risk stratifies patients with DTC. A predictive nomogram using age as a continuous variable may be a more appropriate tool for stratifying patients with DTC and for predicting outcome. PMID- 26148760 TI - Neoadjuvant therapy does not affect lymph node ratio in rectal cancer. AB - AIMS: Recently, lymph-node ratio (LNR) has emerged as a prognostic tool in staging rectal cancer. Studies to date have demonstrated threshold values above and below which survival is differentially altered. Neoadjuvant therapy significantly reduces the number of lymph node retrieved. The aim of the present study was to determine the effect of neoadjuvant therapy on LNR and its prognostic properties. METHODS: Consecutive patients who underwent curative rectal cancer resections in a single institution from 2007 to 2010 were reviewed. LNR was stratified into five subgroups of 0, 0.01-0.17, 0.18-0.41, 0.42-0.69 and 0.7-1.0 based on a previous study. The effect of neoadjuvant therapy on lymph node retrieval, LNR, locoregional (LR) and systemic recurrence (SR), disease-free (DFS) and overall survival (OS) was compared between patients who did (Neoadjuvant) and did not (Surgery Alone) receive neoadjuvant therapy. RESULTS: Neoadjuvant and Surgery Alone groups were comparable in gender, age and tumour stage. The number of lymph nodes retrieved were significantly lower in the Neoadjuvant group (p < 0.01). However, LNR remained similar in both groups (p = 0.36). There was no statistical difference in the DFS and OS between the Neoadjuvant and Surgery Alone groups at the various LNR cut off values in patients with AJCC Stage 3 tumours. CONCLUSIONS: LNR ratio remains unaltered despite reduced lymph node retrieval after neoadjuvant therapy in rectal cancer. LNR may therefore be a more reliable prognostic indicator in this subgroup of patients. PMID- 26148761 TI - The role of simulation in urological training - A quantitative study of practice and opinions. AB - INTRODUCTION: Over the past few decades, simulation-based training has rapidly been adopted by many centres for effective technical and non-technical skills training, as a supplementary method to traditional operating room experience. The aim of this study is to assess the current practice in training and seek opinion regarding the future role of simulation in urological training. METHODS: A cross sectional survey was designed and distributed amongst expert and trainee urological surgeons. The survey consisted of twenty-two questions that were split into three sections; Introduction (6), Technical Skills training in urology (10) and Non-technical skills training in urology (6). RESULTS: A total of 91 residents and 172 specialists completed the survey. In both groups, there was an agreed consensus that laparoscopic training and exposure was insufficient as only 21% of trainees and 23% of specialists believed that they had sufficient training in this area. Furthermore, both groups lacked simulation-based training in common urological procedures including nephrectomy (62%), cystoscopy (69-74%), ureteroscopy (47-59%), transurethral resection of the prostate (56-65%) and percutaneous renal surgery (76-73%). 90% of trainees and 70% of specialists believed (agreed and strongly agreed) that there is a role for non-technical skills simulation in urological training. CONCLUSIONS: Simulation training has been under-used thus far and trainees face an uphill challenge to enhance their skills and technical abilities in the operating room. Simulation is recommended by both trainees and specialists and may represent one of the solutions to the challenges of safe and effective urology procedural training. PMID- 26148762 TI - Point of care optical diagnostic technologies for the detection of oral and oropharyngeal squamous cell carcinoma. AB - BACKGROUND: Despite significant advances in treatment modalities, the 5 year survival rate in oral and oropharyngeal squamous cell carcinoma (SCC) is less than 60%. Clinical examination, white light endoscopy followed by blind biopsies and histopathological analysis remains the gold standard for diagnosis and surveillance. These modalities continue to have a limited diagnostic accuracy of less than 55%. METHODS: Novel optical-based diagnostic methods are promising new technologies for improving both screening and detection of cancer. This review will discuss their role in oral and oropharyngeal cancer detection with particular emphasis on optical imaging in oral and oropharyngeal cancer diagnosis, including the use of surface enhanced Raman spectroscopy, optical coherence tomography, fluorescence diagnosis, confocal laser endomicroscopy, confocal reflectance microscopy and narrow band imaging. RESULTS: Aided by the use of differing wavelengths of light, these methods are capable of detecting physical and biochemical changes that precede and mirror malignant change within tissue. CONCLUSION: Our review of the currently utilized optical diagnostic modalities suggests the possibility of a cost effective, point of care diagnosis that could facilitate early detection, reduce healthcare costs and improve patient survival and quality of life. PMID- 26148763 TI - A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results. AB - BACKGROUND: In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by OnclarityTM (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. METHODS: The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0years. Using stratified random sampling, we typed 2079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1187 with =CIN3 (CIN grade 3 or invasive cancer) as positive. Among 41 CIN grade 2 samples representing an intermediate lesion group, 49% were HPV16 RNA patterns-positive. Interestingly, 3 of 4 HPV16 RNA patterns-positive lesions initially diagnosed as <=CIN1 at follow-up 5-24 months later had progressed to >=CIN2. CONCLUSIONS: We successfully developed and validated a second generation of HPV16 RNA patterns assay by rapid RT-qPCR as triage marker for HPV16 DNA-positive women offering clinical utility to distinguish between the need for immediate colposcopy and continued observation. Limited follow-up data suggests that HPV16 RNA patterns positivity in <=CIN1 lesions can predict disease progression. PMID- 26148765 TI - Expression of cubilin in mouse testes and Leydig cells. AB - Cubilin (cubn) is a receptor for vitamins and various protein ligands. Cubn lacks a transmembrane domain but anchors to apical membranes by forming complexes with Amnionless or Megalin. In an effort to better understand the uptake of nutrients in testis, we analysed cubn expression in the developing mice testes. In testes, cubn mRNA increased from birth to adulthood. In the inter-stitium and isolated seminiferous tubules, neonatal increase in cubn mRNA until 14 days post-partum (pp) was followed by a marked increase at puberty (28 days pp). Cubn was found in the gonocytes, spermatogonia, spermatocytes and spermatids in the developing testes. In adult testes, strong Cubn immunoreactivity was found in the elongating spermatids, suggesting the role of Cubn in endocytosis during early spermiogenesis. In Sertoli cells and peritubular cells, Cubn immunoreactivity was weak throughout the testis development. In the inter-stitium, Cubn immunoreactivity was found in foetal Leydig cells, was weak to negligible in the stem cells and progenitor Leydig cells and was strong in immature and adult Leydig cells, demonstrating a positive association between Cubn and steroidogenic activity of Leydig cells. Collectively, these results suggest that Cubn may participate in the endocytotic uptake of nutrients in germ cells and somatic cells, supporting the spermatogenesis and steroidogenesis in mouse testes. PMID- 26148766 TI - Prognostic significance of abnormal P wave morphology and PR-segment displacement after ST-elevation myocardial infarction. AB - INTRODUCTION: Atrial infarction is uncommonly diagnosed and data on its significance are limited. Its incidence in ST-elevation myocardial infarction (STEMI) reportedly ranges from 0.7-42%. Certain atrial ECG changes, such as abnormal P wave morphology suggestive of atrial involvement have been associated with 90-day mortality after STEMI. However, whether atrial ECG changes are associated with short (30-day) or long-term (1-year) mortality have not been studied. METHODS: We examined index ECG in 224 consecutive STEMI. Demographics, clinical variables, peak troponin I, ejection fraction, and angiographic data were collected. Atrial ECG patterns were examined and correlated with mortality. RESULTS: Length of stay was longer with abnormal P waves (p=0.008) or PR displacement in any lead (p=0.003). Left main coronary disease was more prevalent with abnormal P wave (p=0.045). Abnormal P wave morphology in any lead was associated with higher 30-day (OR 3.09 (1.35-7.05)) and 1-year mortality (OR 5.33 (2.74-10.36)). PR displacement in any lead was also associated with increased 30 day (OR 2.33 (1.03-5.28)) and 1-year mortality (OR 6.56 (3.34-12.86)). Abnormal P wave, PR depression in II, III and AVF, and elevation in AVR or AVL were associated with increased 1-year mortality (OR 12.49 (5.2-30.0)) as was PR depression in the precordial leads (OR 21.65 (6.82-68.66)). After adjusting for age, ejection fraction, peak troponin I, and left main disease, PR displacement in any lead was associated with increased 1-year mortality (adjusted OR 6.22 (2.33-18.64)). CONCLUSION: PR segment displacement in any lead, found in 31% of patients with STEMI, independently predicted 1-year mortality. PMID- 26148767 TI - Takotsubo syndrome after heart valve surgery. PMID- 26148768 TI - Takotsubo cardiomyopathy: Completely simple but not so easy. PMID- 26148769 TI - Natural history of coronary heart disease and heart disease of uncertain etiology: Findings from a 50-year population study. AB - OBJECTIVES: To describe the natural history of common heart disease incidence on a population study. MATERIAL AND METHODS: A sample of 1712 men aged 40-59 was enrolled in 1960 and followed-up for 50years. Coronary heart disease (CHD) was categorized if manifested as sudden death, fatal and non-fatal myocardial infarction and other acute coronary syndromes, and as Heart Disease of Uncertain Etiology (HDUE) if manifested as heart failure, chronic arrhythmia, blocks, diagnoses of chronic CHD or hypertensive heart disease. Their characteristics and prognosis in terms of age at event, mortality and expectancy of life up to 50years were analyzed. RESULTS: Incidence of first CHD and HDUE event or diagnosis was of 26.9 and 20.6%, respectively. First events were equally manifested as fatal or non-fatal occurrences among CHD, while non-fatal occurrences were almost always observed among HDUE. Cases of HDUE presented at a more advanced age and also average age at death was significantly more advanced than in CHD, respectively around 79 and 76years. Expectancy of life was significantly longer for HDUE (30.7years) than for CHD (27.6years). Strokes were more frequently ascertained among HDUE (14%) while 14% of death causes were due to cancer in both CHD and HDUE. Cancers were much higher (40%) among those never diagnosed CHD or HDUE who also had more stroke-due deaths (17%). CONCLUSION: This is the first investigation to report heart disease incidence and its natural history in a quasi-extinction cohort data from Italy in a pre-cardiac surgery era. PMID- 26148770 TI - Early repolarization of surface ECG predicts fatal ventricular arrhythmias in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy and symptomatic ventricular arrhythmias. AB - BACKGROUND: The clinical characteristics and prognostic value of early repolarization (ER) in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and symptomatic ventricular arrhythmias remain unclear. We investigated the prevalence, clinical features, and cardiovascular outcomes of patients with symptomatic ARVD/C and ER. METHODS: A total of 59 consecutive ARVD/C patients hospitalized for catheter ablation, presenting with and without J-point elevations of >=0.1mV in at least 2 inferior leads or lateral leads were enrolled. Clinical characteristics, electrophysiological study, substrate mapping, catheter ablation, and future clinical outcomes in a prospective patient registry were investigated. RESULTS: ER was observed in 38 patients (64.4%). Among these patients, ER was found in the inferior leads in 18 patients (47.4%), in the lateral leads in 2 patients (5.3%), and in both inferior and lateral leads in 18 patients (47.4%). Patients exhibiting ER were commonly men, had lower right ventricular ejection fraction, had higher incidence of clinical ventricular fibrillation or aborted sudden cardiac death, had more defibrillator implantations, had higher the need of epicardial ablation, and had more major criteria according to the task force criteria. Significant higher incidence of induced ventricular fibrillation and shorter tachycardia cycle length of induced ventricular tachycardia were found during procedure. The recurrence rate of ventricular arrhythmias did not differ between patients with and without ER after catheter ablation. CONCLUSIONS: A high prevalence of electrocardiographic ER was found among symptomatic ARVD/C patients undergoing catheter ablation. ER in 12-lead ECG is associated with an increased risk of clinical fatal ventricular arrhythmias. PMID- 26148771 TI - Feasibility of using real-time CMR imaging to evaluate acute thoracic aortic response to exercise. PMID- 26148772 TI - Inconsistency in hemodynamic characterization of severe aortic stenosis. PMID- 26148774 TI - Degree of terrestrial activity of the elusive sun-tailed monkey (Cercopithecus solatus) in Gabon: Comparative study of behavior and postcranial morphometric data. AB - We carried out a multidisciplinary study linking behavioral and morphological data from a little-known guenon species, Cercopithecus solatus, endemic to Gabon. Over a period of 9 months, we documented the pattern of stratum use associated with postural and locomotor behavior by direct observation (650 hrs) of a semi free-ranging breeding colony. We also conducted a morphometric analysis of the humerus and limb proportions of 90 adult specimens from 16 guenon species, including C. solatus. Field observations indicated that C. solatus monkeys spent a third of their time on the ground, similar to semi-terrestrial guenon species. We detected two patterns of stratum use: at ground level, and in trees, at a height of 3-10 m. The monkeys spent more time on the ground during the dry season than the wet season, feeding mainly at ground level, while resting, and social behaviors occurred more frequently in the tree strata. Our study of humerus size and shape, together with the analysis of limb proportions, indicated morphofunctional adaptation of C. solatus to greater terrestriality than previously thought. We therefore characterize C. solatus as a semi-terrestrial guenon, and propose a new hypothesis for the ancestral condition. By combining behavioral and morphological results, we provide new information about the adaptive strategies of the species, and the evolutionary history of guenons, thus contributing to the conservation of the sun-tailed monkey in the wild. PMID- 26148773 TI - Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma. AB - PURPOSE: The major hurdle of current drug carrier against hepatocellular carcinoma (HCC) is the lack of specific and selective drug delivery to HCC. In this study, a novel glycyrrhetinic acid (GA) and poly(L-Histidine) (PHIS) mediated polymeric drug delivery system was developed to target HCC that have GA binding receptors and release its encapsulated anticancer drug in the acidic microenvironment of HCC. METHODS: Firstly, GA and PHIS were conjugated to form poly (ethylene glycol)-poly(lactic-co-glycolic acid) (GA-PEG-PHIS-PLGA, GA-PPP) micelles by grafting reaction between active terminal groups. Secondly, andrographolide (AGP) was encapsulated to GA-PPP to make AGP/GA-PPP using the solvent evaporation method. The pH-responsive property of AGP/GA-PPP micelles was validated by monitoring its stability and drug release behavior in different pH conditions. Furthermore, selective hepatocellular uptake of GA-PPP micelles in vitro, liver specific drug accumulation in vivo, as well as the enhanced antitumor effects of AGP/GA-PPP micelles confirmed the HCC targeting property of our novel drug delivery system. RESULTS: Average size of AGP/GA-PPP micelles increased significantly and the encapsulated AGP released faster in vitro at pH 5.0, while micelles keeping stable in pH 7.4. AGP/GA-PPP micelles were uptaken more efficiently by human Hep3B liver cells than that by human MDA-MB-231 breast cancer cells. GA-PPP micelles accumulated specifically in the liver and possessed long retention time in vivo. AGP/GA-PPP micelles significantly inhibited tumor growth and provided better therapeutic outcomes compared to free AGP and AGP/PEG PLGA(AGP/PP) micelles without GA and PHIS decoration. CONCLUSIONS: This novel GA PPP polymeric carrier is promising for targeted treatment of HCC. PMID- 26148775 TI - Identifying the determinants of use of the G&G interventions for older adults in health and social care: protocol of a multilevel approach. AB - BACKGROUND: Despite aging-related losses, many older adults are able to maintain high levels of subjective well-being. However, not all older adults are able to self-manage and adapt. The GRIP&GLEAM [Dutch: GRIP&GLANS] (G&G) interventions have shown to significantly improve self-management ability, well-being and loneliness in older adults. Actual use of the evidence-based G&G interventions, however, remains limited as long as the interplay between implementation factors at different hierarchical stakeholder levels is poorly understood. The aim of the study is to identify the determinants of successful implementation of the G&G interventions. METHODS/DESIGN: The study is performed in health and social care organizations in the northern part of the Netherlands. The degree of implementation success is operationalized by four parameters: use (yes/no), pace (time to initial use), performance (extent of use) and prolongation (intention to continue use). Based on the Fleuren model, factors at four hierarchical stakeholder levels (i.e. target group, professionals, organizations and financial political context) are assessed at three measurement points in 2 years. The nested data are analyzed applying multilevel modeling techniques. DISCUSSION: In this study, health and social care organizations are considered to be part of multilevel functional systems, in which factors at different hierarchical stakeholder levels impede or facilitate use of the G&G interventions. Strengths of the study are the multifaceted measurement of use, and the multilevel approach in identifying the determinants. The study will contribute to the development of ecologically valid implementation strategies of the G&G interventions and comparable evidence-based practices. PMID- 26148776 TI - Advances in cobalt complexes as anticancer agents. AB - The evolution of resistance to traditional platinum-based anticancer drugs has compelled researchers to investigate the cytostatic properties of alternative transition metal-based compounds. The anticancer potential of cobalt complexes has been extensively studied over the last three decades, and much time has been devoted to understanding their mechanisms of action. This perspective catalogues the development of antiproliferative cobalt complexes, and provides an in depth analysis of their mode of action. Early studies on simple cobalt coordination complexes, Schiff base complexes, and cobalt-carbonyl clusters will be documented. The physiologically relevant redox properties of cobalt will be highlighted and the role this plays in the preparation of hypoxia selective prodrugs and imaging agents will be discussed. The use of cobalt-containing cobalamin as a cancer specific delivery agent for cytotoxins will also be described. The work summarised in this perspective shows that the biochemical and biophysical properties of cobalt-containing compounds can be fine-tuned to produce new generations of anticancer agents with clinically relevant efficacies. PMID- 26148777 TI - Rapid prototyping and patient-specific pre-contoured reconstruction plate for comminuted fractures of the mandible. AB - The clinical use of rapid prototype, 3-dimensional models and pre-bent reconstruction plates is recognised for mandibular reconstruction after resection of cancer. We describe a new approach using similar techniques in the management of complicated mandibular fractures. PMID- 26148778 TI - Trabecular bone score in healthy ageing. AB - OBJECTIVE: The main aim of this work was to report on trabecular bone score (TBS) by dual-energy X-ray absorptiometry (DXA) of healthy Italian subjects to be used as a reference standard for future study in clinical and research settings. The secondary aim was to investigate the link between TBS and conventional parameters of bone and body composition by DXA. METHODS: 250 individuals of 5 age bands (spanning from 18 to 70 years of age, equally distributed for both age and sex) were prospectively recruited. A lumbar spine (LS) DXA scan (Lunar iDXATM; GE Healthcare, Madison, WI) was acquired for each subject and then analysed with the latest version of TBS iNsight v. 2.1 (Med-Imaps, Pessac, France) software. LS bone mineral density (LS BMD), Z-score, T-score and TBS values were collected. Pearson's test was used to investigate the correlations between TBS and LS BMD and the influence of age, body mass index (BMI) and body composition on these parameters. RESULTS: A significant decrease of TBS and LS BMD was observed with ageing in both males (TBS mean values from 1.486 to 1.374; LS BMD mean values from 1.219 to 1.187) and females (TBS mean values from 1.464 to 1.306; LS BMD mean values from 1.154 to 1.116). No statistically significant difference was achieved among males and females of the same age group for both TBS and LS BMD, with the exception of the fifth age group. A significant correlation was found between LS BMD and TBS values in both sexes (r = 0.555-0.655, p < 0.0001). BMI influenced LS BMD but not TBS. TBS values were inversely correlated with some fat mass parameters, in particular with visceral adipose tissue (in males: r = 0.332, p < 0.001; in females: r = -0.348, p < 0.0001). No significant correlation was found between TBS and total lean mass, opposite to LS BMD (in males: r = 0.418; p < 0.0001; in females: r = -0.235; p < 0.001). CONCLUSION: This report is an attempt to start building a database for healthy Italian people providing age- and sex-specific reference curves for TBS. This could help clinicians to improve patient management in the detection of impaired bone mineral status and to monitor bone changes. ADVANCES IN KNOWLEDGE: The study reports TBS values of a selectively enrolled Italian healthy population, ranging from younger to older ages and including males as a reference standard. Moreover, links between body composition and TBS are explored. PMID- 26148779 TI - DNA methylation and gene expression in Mimulus guttatus. AB - BACKGROUND: The presence of methyl groups on cytosine nucleotides across an organism's genome (methylation) is a major regulator of genome stability, crossing over, and gene regulation. The capacity for DNA methylation to be altered by environmental conditions, and potentially passed between generations, makes it a prime candidate for transgenerational epigenetic inheritance. Here we conduct the first analysis of the Mimulus guttatus methylome, with a focus on the relationship between DNA methylation and gene expression. RESULTS: We present a whole genome methylome for the inbred line Iron Mountain 62 (IM62). DNA methylation varies across chromosomes, genomic regions, and genes. We develop a model that predicts gene expression based on DNA methylation (R(2) = 0.2). Post hoc analysis of this model confirms prior relationships, and identifies novel relationships between methylation and gene expression. Additionally, we find that DNA methylation is significantly depleted near gene transcriptional start sites, which may explain the recently discovered elevated rate of recombination in these same regions. CONCLUSIONS: The establishment here of a reference methylome will be a useful resource for the continued advancement of M. guttatus as a model system. Using a model-based approach, we demonstrate that methylation patterns are an important predictor of variation in gene expression. This model provides a novel approach for differential methylation analysis that generates distinct and testable hypotheses regarding gene expression. PMID- 26148780 TI - STD and Abortion Prevalence in Adolescent Mothers With Histories of Childhood Protection Involvement. AB - CONTEXT: Early sexual debut and unprotected sexual activity place adolescents at risk of adverse sexual health outcomes. Adolescents involved with child protective services (CPS) may be a particularly vulnerable population. METHODS: California birth records for 86,946 adolescents who became first-time mothers in 2008-2010 were probabilistically linked to statewide CPS records from 1998 and later. The prevalence of STDs at birth and of abortion history were explored by preconception CPS involvement. Generalized linear models, adjusted for health, socioeconomic and demographic characteristics, were used to assess correlates of current STDs and history of abortion. RESULTS: At the time they gave birth, 1% of adolescents had a documented STD, and 5% reported a previous abortion. After adjustment for other characteristics, CPS involvement was associated with a significantly elevated prevalence both of STDs (relative risk, 1.2) and of previous abortion (1.4). Other characteristics also were associated with both outcomes, but not always in the same direction. For example, delaying prenatal care until after the first trimester or getting none at all was associated with an increased prevalence of STDs (1.3), but a reduced prevalence of abortion (0.8 0.9); having public insurance coverage for the birth was associated with a reduced STD prevalence (0.9) and an elevated abortion history prevalence (1.2). CONCLUSIONS: To assess whether adolescents with a history of CPS involvement need targeted sexual health interventions, further research is needed on the mechanisms that underlie associations between CPS involvement and adverse sexual health outcomes. PMID- 26148781 TI - Laparoscopic colonic resection for splenic flexure cancer: our experience. AB - BACKGROUND: The treatment of colon cancer located in splenic flexure is not standardized. Laparoscopic approach is still considered a challenging procedure. This study reviews two Institutions experience in laparoscopic treatment of left colonic flexure cancer. Intraoperative, pathologic and postoperative data from patients undergoing laparoscopic splenic flexure resection were analyzed to assess oncological safety as well as early and medium-term outcomes. METHODS: From October 2005 to May 2014 laparoscopic splenic flexure resection was performed in 23 patients. RESULTS: Conversion rate was nihil. In 7 cases the anastomosis was performed intracorporeally. Specimen mean length was 21.2 cm, while the distance of distal and proximal resection margin from tumor site was 6.5 and 11.5 respectively. The mean number of harvested lymph nodes was 20.8. Mean operative time was 190 min and mean estimated blood loss was equal to 55 ml. As regard major postoperative complications, one case of postoperative acute pancreatitis and one case of postoperative bleeding from the anastomotic suture line were reported. CONCLUSIONS: Although our experience is limited and appropriate indications must be set by future randomized studies, we believe that laparoscopic resection with intracorporeal anastomosis appears feasible and safe for patients affected by splenic flexure cancer. PMID- 26148782 TI - Ovarian Cyst Aspiration in the Neonate: Minimally Invasive Surgery. AB - STUDY OBJECTIVE: To review our experience with laparoscopic aspirations and minimally invasive surgeries for neonatal ovarian cysts and report the outcome of their follow-up. DESIGN: Twenty-one neonates diagnosed as having ovarian cysts were retrospectively reviewed at our hospital from 2006 through 2013. RESULTS: Of 21 neonates, 8 showed simple cysts and 13 showed complex cysts in their ultrasound scan. Laparoscopic aspiration was performed for all neonates with simple cysts. Torsion was found in 7 of 13 neonates with complex cysts. Three neonates underwent detorsion, while 2 neonates underwent oophorectomy. Two neonates already showed autoligation, showing a cystic mass, which was removed. The remaining 6 neonates with a complex cyst underwent only aspiration because no torsion was found. Of 14 neonates who underwent only aspiration, 11 showed no cyst, while 3 neonates, having a cyst with a size of less than 2 cm, underwent follow-up. Of 3 neonates who underwent detorsion, 1 showed an ovary without cyst, while 2 showed neither cyst nor ovary. CONCLUSION: Laparoscopically, neonatal ovarian cysts may be diagnosed and aspirated simultaneously, simply, and safely. PMID- 26148783 TI - Risk of Malignancy and Need for Surgery in Pediatric Patients with Morris or Y chromosome Turner Syndrome: A Multicenter Survey. AB - STUDY OBJECTIVE: The management of intersex patients with Y-chromosome Turner or Morris syndrome remains a challenge. We report our experience with a multicenter European survey. DESIGN: We collected the data on 18 patients (mean age 10.2 years, range 2-17 years) with Morris (10 patients) or Turner (8 patients) syndrome harboring the Y chromosome who were treated in 1 of 6 European centers of pediatric surgery between 1997 and 2013. All patients were evaluated by use of a multidisciplinary diagnostic protocol. All patients received a bilateral gonadectomy via laparoscopy; only 1 center performed ovarian cryopreservation. Seven patients received a concomitant genitoplasty. Operative notes and histology were reviewed for details. RESULTS: No conversions to laparotomy and no complications were recorded. For the patients receiving only the gonadectomy, the length of hospital stay was 24-48 hours, whereas for the patients receiving an associated genitoplasty, it was 6-10 days. Specimens were negative for tumors in 83.3% of cases, whereas in 3 patients (16.6%), benign abnormalities (Sertoli cell hyperplasia in 1 patient and ovotestis in 2 patients) were recorded. A malignant tumor was not recorded in our series. CONCLUSION: If the risk of malignancy is considered as the main indication for surgery in case of Turner or Morris syndrome, on the basis of our study, this indication should be reevaluated. However, based on the non-negligible rate of benign abnormalities reported in our series (16.6%), the performance of cryopreservation to preserve fertility and the possibility of performing genitoplasty during the same anesthetic procedure represent additional valid indications for surgery. PMID- 26148784 TI - Emergency Contraception Pill Awareness and Knowledge in Uninsured Adolescents: High Rates of Misconceptions Concerning Indications for Use, Side Effects, and Access. AB - STUDY OBJECTIVE: To determine the awareness of, access to, and knowledge of the proper use of emergency contraception pills (ECPs) among uninsured adolescents. DESIGN: Anonymous surveys were used to assess awareness of, knowledge of, and access to ECPs. SETTING: From 2010 to 2012 at mobile primary care clinic in the San Francisco Bay Area. PARTICIPANTS: Patients were uninsured adolescents aged 13 to 25; 40% of the participants were currently or had been homeless in the past year. Ethnicity was 50% Asian, 22% Hispanic, 17% Pacific Islanders, 5.5% white, and 5.5% other/mixed ethnicity. INTERVENTIONS: Post survey completion, patients received one-on-one 15-minute dedicated ECP education. MAIN OUTCOME MEASURES: Awareness of, knowledge of, and access to ECPs. RESULTS: Of the study population of 439, 30% of the participants were 13-16 years old and 70% were 17-25 years old (mean age 17.8 years); 66% were women. Young women (86%) reported higher rates of "hearing about emergency contraception" than did young men (70%) (P < .0001). Many incorrectly identified or were uncertain if ECPs were an abortion pill (40%) or could be used as regular birth control (40%) or to prevent sexually transmitted infections (19%). Only 40% of women and 43% of men aged 17 and older correctly answered that they could obtain EC over the counter; 72% did not know that males could receive EC for use by their partner; 12% incorrectly selected that infertility was a side effect; 44% were under the false impression that EC had to be taken within 1 day of unprotected sex. CONCLUSIONS: Uninsured adolescents have high rates of ECP awareness but low ECP knowledge. These adolescents need more ECP education to alleviate misconceptions and increase practical knowledge, specifically, education about male access, side effects, over-the-counter availability for young men and women, and the 120-hour window of use. PMID- 26148785 TI - Typical and Atypical Associated Findings in a Group of 346 Patients with Mayer Rokitansky-Kuester-Hauser Syndrome. AB - STUDY OBJECTIVE: The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is characterized by vaginal and uterine aplasia in a 46,XX individual. Multiple abnormalities may be associated with MRKH syndrome, and it appears to overlap other syndromes. The aim of this study was to describe the spectrum of associated malformations and syndromes as well as abnormal karyotypic findings in a large cohort of 346 patients. DESIGN, SETTING, AND PARTICIPANTS: The study is a retrospective analysis of 346 MRKH patients treated in the University Hospital in Tuebingen between 1998 and 2013. MAIN OUTCOME MEASURES: The dataset was screened for typical associated malformations as well as atypical malformations and abnormal karyotypes. A complete review of the literature was included. RESULTS: Among our cohort of 346 patients, we found that 53.2% had MRKH type 1, 41.3% had MRKH type 2, and 5.5% had MURCS syndrome. The group with associated malformations included 57.6% renal, 44.4% skeletal, and 30.8% other malformations. Additionally, we found 2 cases of absent radius syndrome, 3 cases of anal atresia, and 1 patient with oculodentodigital dysplasia, and other atypical malformations. Abnormal karyotypes were found in 5 cases, and 39 siblings and 11 parents had known malformations. CONCLUSIONS: This study supports the hypothesis that the syndrome has a multifactorial pathogenesis. With the high numbers of associated malformations reported in this study, patients with MRKH syndrome should be regarded as having a complex syndrome. Molecular-genetic analyses in larger numbers of children after surrogacy, twin pregnancies, and familial cases may make it possible to obtain further information about the etiology of the syndrome. PMID- 26148786 TI - Do State-Based Policies Have an Impact on Teen Birth Rates and Teen Abortion Rates in the United States? AB - OBJECTIVES: The United States has one of the highest teen birth rates among developed countries. Interstate birth rates and abortion rates vary widely, as do policies on abortion and sex education. The objective of our study is to assess whether US state-level policies regarding abortion and sexual education are associated with different teen birth and teen abortion rates. METHODS: We carried out a state-level (N = 51 [50 states plus the District of Columbia]) retrospective observational cross-sectional study, using data imported from the National Vital Statistics System. State policies were obtained from the Guttmacher Institute. We used descriptive statistics and regression analysis to study the association of different state policies with teen birth and teen abortion rates. RESULTS: The state-level mean birth rates, when stratifying between policies protective and nonprotective of teen births, were not statistically different-for sex education policies, 39.8 of 1000 vs 45.1 of 1000 (P = .2187); for mandatory parents' consent to abortion 45 of 1000, vs 38 of 1000 when the minor could consent (P = .0721); and for deterrents to abortion, 45.4 of 1000 vs 37.4 of 1000 (P = .0448). Political affiliation (35.1 of 1000 vs 49.6 of 1000, P < .0001) and ethnic distribution of the population were the only variables associated with a difference between mean teen births. Lower teen abortion rates were, however, associated with restrictive abortion policies, specifically lower in states with financial barriers, deterrents to abortion, and requirement for parental consent. CONCLUSION: While teen birth rates do not appear to be influenced by state-level sex education policies, state-level policies that restrict abortion appear to be associated with lower state teen abortion rates. PMID- 26148787 TI - Surgical Approach to Ovarian Torsion in Children. AB - STUDY OBJECTIVE: Ovarian torsion in children is a relatively rare cause of acute abdominal pain. This study evaluates the diagnosis and treatment of ovarian torsion with an emphasis on conservative treatment approaches including the long term follow-up results. DESIGN AND PARTICIPANTS: Patients with surgically treated ovarian torsions between December 2006 and February 2014 were included in this retrospective study. The patient population consisted of 41 patients with 42 ovaries involved. The mean age was 11 +/- 3.9 (range, 1-17) years. The most common presenting symptom was abdominal pain. INTERVENTION: All patients underwent preoperative pelvic color Doppler ultrasonography that identified torsion in 34 (81%) ovaries. RESULTS: During surgery, a right-sided torsion was detected in 25 (59.5%), and a left-sided one was detected in 17 (40.5%) ovaries. An excisional surgery was used for 16 (38%) ovaries, and detorsion with conservation of the ovary was used for 26 (62%). A trend toward conservative management was seen over the years. Regular follow-up for those patients who underwent conservative surgery was done in 22 patients for a mean of 25 months (range, 1.5-83 months). Control color Doppler ultrasonographic results were within normal limits in terms of ovarian size and blood supply in 17 (77%) patients. Despite normal parenchymal echogenicity, an involved ovary was smaller in size compared to the other ovary in five patients. Ovarian follicles were present in three of them. CONCLUSION: The ovary-sparing, conservative surgery is found to be highly successful in the presented series. Although malignancies are rarely encountered in torsed ovaries with associated masses, biopsy samples should be obtained in suspicious cases. PMID- 26148788 TI - Laparoscopic Nerve-Preserving Colposacropexy for Surgical Management of Neovaginal Prolapse. AB - BACKGROUND: Neovaginal prolapse occurs rarely, and a standard treatment has not yet been defined. CASE: We report 2 cases of patients with vaginal agenesis with a symptomatic neovaginal prolapse; one occurring 25 years after self-dilation and another occurring 24 years after sigmoid vaginoplasty. At 48 and 18 months after surgical treatment with laparoscopic nerve-preserving colposacropexy using 2 types of mesh and 2 kinds of sutures to anchor the mesh at the neovaginal wall, both women are asymptomatic and highly satisfied with the result, without prolapse recurrence or mesh/suture erosion. SUMMARY AND CONCLUSION: For the surgical management of neovaginal prolapse after sigmoid vaginoplasty and vagina creation after self-dilation, we recommend the nerve-preserving sacrocolpopexy as a safe method to achieve durable functional outcomes and good anatomic vaginal level I and II support. PMID- 26148789 TI - Multivariate classification of autism spectrum disorder using frequency-specific resting-state functional connectivity--A multi-center study. AB - BACKGROUND: Resting-state functional magnetic resonance imaging studies examining low frequency fluctuations (0.01-0.08 Hz) have revealed atypical whole brain functional connectivity patterns in adolescents with autism spectrum disorder (ASD), and these atypical patterns can be used to discriminate individuals with ASD from controls. However, at present it is unknown whether functional connectivity at specific frequency bands can be used to discriminate individuals with ASD from controls, and whether relationships with symptom severity are stronger in specific frequency bands. METHODS: We selected 240 adolescent subjects (12-18 years old, 112 with autism spectrum disorder (101/11, males/females) and 128 healthy controls (104/24, males/females)) from 6 separate international sites in the Autism Brain Imaging Data Exchange database. Whole brain functional connectivity networks were constructed in the Slow-5 (0.01-0.027 Hz) and Slow-4 (0.027-0.073 Hz) frequency bands, which were then used as classification features. RESULTS: An accuracy of 79.17% (p<0.001) was obtained using support vector machine. Most of the discriminative features were concentrated on the Slow-4 band. In the Slow-4 band, atypical connections between the default mode network, fronto-parietal network and cingulo-opercular network were detected. A significant correlation was found between social and communication deficits as measured by the ADOS in individuals with ASD and the classification scores based on connectivity between the default mode network and the cingulo-opercular network. Connections of the thalamus were of the highest classification weight in the Slow-4 band. CONCLUSIONS: Our findings provide preliminary evidence for frequency-specific whole brain functional connectivity indices that may eventually be used to aid detection of ASD. PMID- 26148790 TI - Enhancing adherence in trials promoting change in diet and physical activity in individuals with a diagnosis of colorectal adenoma; a systematic review of behavioural intervention approaches. AB - BACKGROUND: Little is known about colorectal adenoma patients' ability to adhere to behavioural interventions promoting a change in diet and physical activity. This review aimed to examine health behaviour intervention programmes promoting change in diet and/or physical activity in adenoma patients and characterise interventions to which this patient group are most likely to adhere. METHODS: Searches of eight databases were restricted to English language publications 2000 2014. Reference lists of relevant articles were also reviewed. All randomised controlled trials (RCTs) of diet and physical activity interventions in colorectal adenoma patients were included. Eligibility and quality were assessed and data were extracted by two reviewers. Data extraction comprised type, intensity, provider, mode and location of delivery of the intervention and data to enable calculation of four adherence outcomes. Data were subject to narrative analysis. RESULTS: Five RCTs with a total of 1932 participants met the inclusion criteria. Adherence to the goals of the intervention ranged from 18 to 86 % for diet and 13 to 47 % for physical activity. Diet interventions achieving >= 50 % adherence to the goals of the intervention were clinic based, grounded in cognitive theory, delivered one to one and encouraged social support. CONCLUSIONS: The findings of this review indicate that behavioural interventions can encourage colorectal adenoma patients to improve their diet. This review was not however able to clearly characterise effective interventions promoting increased physical activity in this patient group. Further research is required to establish effective interventions to promote adherence to physical activity in this population. PMID- 26148791 TI - Association between volume of severely injured patients and mortality in German trauma hospitals. AB - BACKGROUND: The issue of patient volume related to trauma outcomes is still under debate. This study aimed to investigate the relationship between number of severely injured patients treated and mortality in German trauma hospitals. METHODS: This was a retrospective analysis of the TraumaRegister DGU(r) (2009 2013). The inclusion criteria were patients in Germany with a severe trauma injury (defined as Injury Severity Score (ISS) of at least 16), and with data available for calculation of Revised Injury Severity Classification (RISC) II score. Patients transferred early were excluded. Outcome analysis (observed versus expected mortality obtained by RISC-II score) was performed by logistic regression. RESULTS: A total of 39,289 patients were included. Mean(s.d.) age was 49.9(21.8) years, 27,824 (71.3 per cent) were male, mean(s.d.) ISS was 27.2(11.6) and 10,826 (29.2 per cent) had a Glasgow Coma Scale score below 8. Of 587 hospitals, 98 were level I, 235 level II and 254 level III trauma centres. There was no significant difference between observed and expected mortality in volume subgroups with 40-59, 60-79 or 80-99 patients treated per year. In the subgroups with 1-19 and 20-39 patients per year, the observed mortality was significantly greater than the predicted mortality (P < 0.050). High-volume hospitals had an absolute difference between observed and predicted mortality, suggesting a survival benefit of about 1 per cent compared with low-volume hospitals. Adjusted logistic regression analysis (including hospital level) identified patient volume as an independent positive predictor of survival (odds ratio 1.001 per patient per year; P = 0.038). CONCLUSION: The hospital volume of severely injured patients was identified as an independent predictor of survival. A clear cut-off value for volume could not be established, but at least 40 patients per year per hospital appeared beneficial for survival. PMID- 26148792 TI - In situ microscopic observation of chitin and fungal cells with chitinous cell walls in hydrothermal conditions. AB - Recent findings of intact chitin in fossil records suggest surprisingly high recalcitrance of this biopolymer during hydrothermal treatments. We also know in the experience of everyday life that mushroom, cells of which have chitinous cell walls, do not fall apart however long they are simmered. We used in situ optical microscopy to examine chitin and fungal cells with chitinous cell walls during hydrothermal treatments, and obtained direct evidence that they remained undegraded at temperatures well over 200 degrees C. The results show very hot and compressed water is needed to make mushrooms mushy. PMID- 26148793 TI - Synthesis of Carfentanil Amide Opioids Using the Ugi Multicomponent Reaction. AB - We report a novel approach to synthesize carfentanil amide analogues utilizing the isocyanide-based four-component Ugi multicomponent reaction. A small library of bis-amide analogues of carfentanil was created using N-alkylpiperidones, aniline, propionic acid, and various aliphatic isocyanides. Our lead compound showed high affinity for mu (MOR) and delta opioid receptors (DOR) with no appreciable affinity for kappa (KOR) receptors in radioligand binding assays. The compound was found to be a mixed MOR agonist/partial DOR agonist in [(35)S]GTPgammaS functional assays, and it showed moderate analgesic potency in vivo. The compound showed no visible signs of physical dependence or constipation in mice. In addition, it produced less respiratory depression than morphine. Most mixed MOR/DOR opioids reported in the literature are peptides and thereby systemically inactive. Our approach utilizing a multicomponent reaction has the promise to deliver potent and efficacious small-molecule analgesics with potential clinical utility. PMID- 26148795 TI - Concept analysis of recovery in mental illness in young adulthood. AB - Recovery, as a concept, emerged as a core philosophy of the service user movement that began in the late 1960s and 1970s. Previous reviews on recovery in mental health have presented definitions or a conceptual framework; however, over time it has been open to disparate interpretations. The aim of this paper was to conduct the first concept analysis of mental health recovery in young adulthood within various multidisciplinary contexts. Rodgers's (2000) six-stepped evolutionary method enabled the analysis of recovery's conceptual characteristics, the identification of an exemplar and the proposition of a hypothesis with implications for practice. This analysis has revealed the derivation of the term recovery does not convey its identified conceptual characteristics. Identified attributes include the reawakening of hope, reclaiming a positive self and meaning through personal growth. Antecedents include the disruption of illness, stigmatization, internal inventory and contemplative recovery. Identified consequences include the return to normality, reconstruction of self and active social connection. The new conceptual definition is the reawakening of hope and rediscovery of a positive sense of self through finding meaning and purpose within personal growth and connection using creative self-care coping strategies. This paper reveals an apparent disparity between professional and personal interpretations of recovery. Therefore, the implication for mental health nursing is the congruence of recovery-orientated practice with the process of recovery experienced by young adult service users. PMID- 26148794 TI - Evaluation of S100B in the diagnosis of suspected intracranial hemorrhage after minor head injury in patients who are receiving platelet aggregation inhibitors and in patients 65 years of age and older. AB - OBJECT: Cranial CT (CCT) scans and hospital admission are increasingly performed to rule out intracranial hemorrhage in patients after minor head injury (MHI), particularly in older patients and in those receiving antiplatelet therapy. This leads to high radiation exposure and a growing financial burden. The aim of this study was to determine whether the astroglial-derived protein S100B that is released into blood can be used as a reliable negative predictive tool for intracranial bleeding in patients after MHI, when they are older than 65 years or being treated with antiplatelet drugs (low-dose aspirin, clopidogrel). METHODS: The authors conducted a prospective observational study in 2 trauma hospitals. A total of 782 patients with MHI (Glasgow Coma Scale Score 13-15) who were on medication with platelet aggregation inhibitors (PAIs) or were age 65 years and older, independent of antiplatelet therapy, were included. Clinical examination, bloodwork, observation, and CCT were performed in the traumatology emergency departments. When necessary, patients were admitted and observation took place on the ward; in these patients, CCT was performed during their hospital stay. Patients with severe trauma, focal neurological deficits, posttraumatic seizures, anticoagulant therapy, alcohol intoxication, coagulation disorder, blood sampling more than 3 hours after trauma, and unknown time of the trauma were excluded from the study. The median age of the patients was 83 years, and 69% were female. Sensitivity, specificity, and positive and negative predictive values of S100B with reference to CCT findings were calculated. The cutoff of S100B was set at 0.105 MUg/L. RESULTS: Of the 782 patients, 50 (6.4%) had intracranial bleeding. One patient with positive results on CCT scan showed an S100B level below 0.105 MUg/L. Of all patients, 33.1% were below the cutoff. S100B showed a sensitivity of 98.0% (CI 89.5%-99.7%), a negative predictive value of 99.6% (CI 97.9%-99.9%), a specificity of 35.3% (CI 31.9%- 38.8%), and a positive predictive value of 9.4% (CI 7.2%-12.2%). CONCLUSIONS: Levels of S100B below 0.105 MUg/L can accurately predict normal CCT findings after MHI in older patients and in those treated with PAIs. Combining conventional decision criteria with measurement of S100B can reduce the CCT scan and hospital admission rates by approximately 30%. PMID- 26148796 TI - Distinct Protein Expression Profiles of Solid-Pseudopapillary Neoplasms of the Pancreas. AB - Solid-pseudopapillary neoplasm (SPN) is an uncommon pancreatic tumor with mutation in CTNNB1 and distinct clinical and pathological features. We compared the proteomic profiles of SPN to mRNA expression. Pooled SPNs and pooled non neoplastic pancreatic tissues were examined with high-resolution mass spectrometry. We identified 329 (150 up-regulated and 179 down-regulated) differentially expressed proteins in SPN. We identified 191 proteins (58.1% of the 329 dysregulated proteins) with the same expression tendencies in SPN based on mRNA data. Many overexpressed proteins were related to signaling pathways known to be activated in SPNs. We found that several proteins involved in Wnt signaling, including DKK4 and beta-catenin, and proteins that bind beta-catenin, such as FUS and NONO, were up-regulated in SPNs. Molecules involved in glycolysis, including PKM2, ENO2, and HK1, were overexpressed in accordance to their mRNA levels. In summary, SPN showed (1) distinct protein expression changes that correlated with mRNA expression, (2) overexpression of Wnt signaling proteins and proteins that bind directly to beta-catenin, and (3) overexpression of proteins involved in metabolism. These findings may help develop early diagnostic biomarkers and molecular targets. PMID- 26148797 TI - Blood lipid levels associate with childhood asthma, airway obstruction, bronchial hyperresponsiveness, and aeroallergen sensitization. AB - BACKGROUND: Studies of children's blood lipid profiles in relation to asthma are few, and the results are ambiguous. OBJECTIVE: We sought to examine whether the lipid profile is associated with concurrent asthma, altered lung function, and allergic sensitization in children. METHODS: High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were measured at ages 5 to 7 years in the Copenhagen Prospective Studies on Asthma in Childhood2000 at-risk birth cohort. Asthma and allergic rhinitis were diagnosed based on predefined algorithms at age 7 years along with assessments of lung function, bronchial responsiveness, fraction of exhaled nitric oxide (Feno), and allergic sensitization. Associations between lipid levels and clinical outcomes were adjusted for sex, passive smoking, and body mass index. RESULTS: High levels of low-density lipoprotein cholesterol were associated with concurrent asthma (adjusted odds ratio [aOR], 1.93; 95% CI, 1.06-3.55; P = .03) and airway obstruction: 50% of forced expiratory flow (abeta coefficient, -0.13 L/s; 95% CI, -0.24 to -0.03 L/s; P = .01) and specific airway resistance (abeta coefficient, 0.06 kPa/s; 95% CI, 0.00-0.11 kPa/s; P = .05). High levels of high-density lipoprotein cholesterol were associated with improved specific airway resistance (abeta coefficient, -0.11 kPa/s; 95% CI, -0.21 to -0.02; P = .02), decreased bronchial responsiveness (abeta coefficient, 0.53 log-MUmol; 95% CI, 0.00-1.60 log-MUmol; P = .05), decreased risk of aeroallergen sensitization (aOR, 0.27; 95% CI, 0.01-0.70; P = .01), and a trend of reduced Feno levels (abeta coefficient, 0.22 log-ppb; 95% CI, -0.50 to 0.01 log-ppb; P = .06). High triglyceride levels were associated with aeroallergen sensitization (aOR, 2.01; 95% CI, 1.14-3.56; P = .02) and a trend of increased Feno levels (abeta coefficient, 0.14 log-ppb; 95% CI, -0.02 to 0.30 log-ppb; P = .08). CONCLUSION: The blood lipid profile is associated with asthma, airway obstruction, bronchial responsiveness, and aeroallergen sensitization in 7-year-old children. These findings suggest that asthma and allergy are systemic disorders with commonalities with other chronic inflammatory disorders. PMID- 26148798 TI - Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle cells from asthmatic patients. AB - BACKGROUND: Aberrant expression of small noncoding RNAs (sncRNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) in particular, define several pathologic processes. Asthma is characterized by airway hyperreactivity, chronic inflammation, and airway wall remodeling. Asthma-specific miRNA profiles were reported for bronchial epithelial cells, whereas sncRNA expression in asthmatic bronchial smooth muscle (BSM) cells is almost completely unexplored. OBJECTIVE: We sought to determine whether the primary BSM sncRNA expression profile is altered in asthmatic patients and identify targets of differentially expressed sncRNAs. METHODS: Small RNA sequencing was used for sncRNA profiling in BSM cells (from 8 asthmatic and 6 nonasthmatic subjects). sncRNA identification and differential expression analysis was performed with iMir software. Experimentally validated miRNA targets were identified by using Ingenuity Pathway Analysis, and putative piRNA targets were identified by using miRanda software. RESULTS: BSM cells from asthmatic patients showed abnormal expression of 32 sncRNAs (26 miRNAs, 5 piRNAs, and 1 small nucleolar RNA). Target prediction for deregulated miRNAs and piRNAs revealed experimentally validated and predicted mRNA targets expressed in the BSM cells. Thirty-eight of these mRNAs represent major targets for deregulated miRNAs and might play important roles in the pathophysiology of asthma. Interestingly, 6 of these mRNAs were previously associated with asthma, considered as novel therapeutic targets for treatment of this disease, or both. Signaling pathway analysis revealed involvement of 38 miRNA-targeted mRNAs in increased cell proliferation through phosphatase and tensin homolog and phosphoinositide 3-kinase/Akt signaling pathways. CONCLUSIONS: BSM cells of asthmatic patients are characterized by aberrant sncRNA expression that recapitulates multiple pathologic phenotypes of these cells. PMID- 26148799 TI - Mode of delivery--impact on risk of noncommunicable diseases. PMID- 26148800 TI - Effects on the metabolism, growth, digestive capacity and osmoregulation of juvenile of Sub-Antarctic Notothenioid fish Eleginops maclovinus acclimated at different salinities. AB - In this study we assessed the influence of three different environmental salinities (5, 15 and 31 psu during 90 days) on growth, osmoregulation, energy metabolism and digestive capacity in juveniles of the Notothenioid fish Eleginops maclovinus. At the end of experimental time samples of plasma, liver, gill, intestine, kidney, skeletal muscle, stomach and pyloric caeca were obtained. Growth, weight gain, hepatosomatic index and specific growth rate increased at 15 and 31 psu and were lower at 5 psu salinity. Gill Na(+), K(+)-ATPase (NKA) activity presented a "U-shaped" relationship respect to salinity, with its minimum rates at 15 psu, while this activity correlated negatively with salinity at both anterior and posterior intestinal portions. No significant changes in NKA activity were observed in kidney or mid intestine. Large changes in plasma, metabolite levels and enzymatic activities related to energy metabolism in liver, gill, intestine, kidney and muscle were generally found in the groups exposed to 5 and 31 psu compared to the 15 psu group. Only the pepsin activity (digestive enzymes) assessed enhanced with environmental salinity, while pyloric caeca trypsin/chymotrypsin ratio decreased. This study suggests that juvenile of E. maclovinus presents greater growth near its iso-osmotic point (15 psu) and hyperosmotic environment (31 psu). Acclimation to low salinity increased the osmoregulatory expenditure as seen by the gill and anterior intestine results, while at high salinity, branchial osmoregulatory activity was also enhanced. This requires the mobilization of lipid stores and amino acids, thereby holding the growth of fish back. The subsequent reallocation of energy sources was not sufficient to maintain the growth rate of fish exposed to 5 psu. Thus, E. maclovinus juveniles present better growth efficiencies in salinities above the iso-osmotic point and hyperosmotic environment of this species, showing their best performance at 15 psu as seen by the main osmoregulatory and energy metabolism enzymatic activities. PMID- 26148801 TI - Abundance of infiltrating CD163+ cells in the retina of postmortem eyes with dry and neovascular age-related macular degeneration. AB - PURPOSE: Prior research in animal models has suggested that retinal macrophages play an important role in age-related macular degeneration (AMD), but studies have insufficiently characterized the distribution of retinal macrophages in various stages of human AMD. METHODS: In this case series, we analyzed H&E, periodic acid-Schiff, and CD163 and CD68 immunostained slides from 56 formaldehyde-fixed, paraffin-embedded autopsy eyes of patients over age 75: 11 age-matched, normal eyes, and 45 AMD eyes. RESULTS: Qualitative analysis of the macula and retinal periphery revealed that all eyes contained a significant number of CD163+ cells but a negligible number of CD68+ cells. In normal eyes and eyes with thin or infrequent basal laminar deposits, CD163+ cells were restricted to the inner retina. In contrast, in AMD eyes with thick basal deposits, choroidal neovascular membranes, and geographic atrophy, qualitatively there was a marked increase in the number and size of the CD163+ cells in the outer retina, sub-retinal, and sub-retinal pigment epithelium space in the macula. CONCLUSIONS: The changes in number and localization of retinal CD163+ cells in eyes with intermediate-severe AMD support a key role for macrophages in the pathogenesis and progression of the disease. A larger, quantitative study evaluating the distribution of macrophage subpopulations in postmortem AMD eyes is warranted. PMID- 26148802 TI - Anti-VEGF therapy in symptomatic peripheral exudative hemorrhagic chorioretinopathy (PEHCR) involving the macula. AB - INTRODUCTION: The purpose of this study was to describe the anatomical and functional outcome of vascular endothelial growth factor inhibitor (anti-VEGF) treatment in symptomatic peripheral exudative hemorrhagic chorioretinopathy (PEHCR) involving the macula. METHODS: Clinical records from patients seen between 2012 and 2013 at a single academic center were reviewed to identify PEHCR patients receiving anti-VEGF therapy due to disease-associated changes involving the macula. Affected eyes were either treated with consecutive intravitreal injections of anti-VEGF or vitrectomy combined with anti-VEGF followed by pro re nata injections. RESULTS: The mean age of the patients was 76 years (range 70-89 years). In all nine eyes, visual acuity was reduced due to central subretinal fluid. On average, three anti-VEGF injections (range 2-5 injections) were required initially to achieve complete resolution of macular subretinal fluid. In three eyes, subretinal fluid reappeared after an average of 10 months (range 5-16 months), and an average of 2.5 anti-VEGF injections (range 2-3 injections) were necessary to attain complete resolution of macular subretinal fluid a second time. Median visual acuity at the visit before the first injection was 1.0 logMAR (range 2.1-0.4 logMAR) and increased to 0.8 logMAR (range 2-0.1 logMAR) at the last visit. CONCLUSION: Results of this study show that for cases in which PEHCR becomes symptomatic due to macular involvement, anti-VEGF treatment may have drying potential. Although vision was improved in some patients, it remained limited in cases with long-term macular involvement, precluding any definitive functional conclusion. However, we believe that the use of anti-VEGF agents should be recommended in PEHCR that threatens the macula. Due to its often self limiting course, peripheral lesions should be closely observed. Larger studies are needed in order to provide clear evidence of the efficacy of anti-VEGF therapy in PEHCR. PMID- 26148803 TI - New avenues for ligand-mediated processes--expanding metal reactivity by the use of redox-active catechol, o-aminophenol and o-phenylenediamine ligands. AB - Redox-active ligands have evolved from being considered spectroscopic curiosities - creating ambiguity about formal oxidation states in metal complexes - to versatile and useful tools to expand on the reactivity of (transition) metals or to even go beyond what is generally perceived possible. This review focusses on metal complexes containing either catechol, o-aminophenol or o-phenylenediamine type ligands. These ligands have opened up a new area of chemistry for metals across the periodic table. The portfolio of ligand-based reactivity invoked by these redox-active entities will be discussed. This ranges from facilitating oxidative additions upon d(0) metals or cross coupling reactions with cobalt(iii) without metal oxidation state changes - by functioning as an electron reservoir - to intramolecular ligand-to-substrate single-electron transfer to create a reactive substrate-centered radical on a Pd(ii) platform. Although the current state-of-art research primarily consists of stoichiometric and exploratory reactions, several notable reports of catalysis facilitated by the redox-activity of the ligand will also be discussed. In conclusion, redox-active ligands containing catechol, o-aminophenol or o-phenylenediamine moieties show great potential to be exploited as reversible electron reservoirs, donating or accepting electrons to activate substrates and metal centers and to enable new reactivity with both early and late transition as well as main group metals. PMID- 26148805 TI - Frailty and Dialysis Initiation. PMID- 26148807 TI - Real-time Imaging of Rabies Virus Entry into Living Vero cells. AB - Understanding the mechanism of rabies virus (RABV) infection is vital for prevention and therapy of virulent rabies. However, the infection mechanism remains largely uncharacterized due to the limited methods and viral models. Herein, we utilized a powerful single-virus tracking technique to dynamically and globally visualize the infection process of the live attenuated rabies vaccine strain-SRV9 in living Vero cells. Firstly, it was found that the actin-enriched filopodia is in favor of virus reaching to the cell body. Furthermore, by carrying out drug perturbation experiments, we confirmed that RABV internalization into Vero cells proceeds via classical dynamin-dependent clathrin mediated endocytosis with requirement for intact actin, but caveolae-dependent endocytosis is not involved. Then, our real-time imaging results unambiguously uncover the characteristics of viral internalization and cellular transport dynamics. In addition, our results directly and quantitatively reveal that the intracellular motility of internalized RABV particles is largely microtubule dependent. Collectively, our work is crucial for understanding the initial steps of RABV infection, and elucidating the mechanisms of post-infection. Significantly, the results provide profound insight into development of novel and effective antiviral targets. PMID- 26148808 TI - [Osteochondral fractures at the knee joint]. AB - Osteochondral fractures are traumatic shearing injuries to the cartilage and the subchondral bone which lead to defects in the articular surface and potentially lead to further degeneration and arthritis. Early diagnosis and therapy are therefore very important. As the resolving power of conventional X-rays is limited for this situation, magnetic resonance imaging (MRI) is regarded as the gold standard for diagnostics. Concomitant injuries often occur, such as tearing of the anterior cruciate ligament (ACL) or patellar dislocation resulting in instability of the patella. Concerning treatment options for osteochondral fractures, there are two potential strategies that can be applied: the first is removal of small osteochondral fragments with subsequent formation of regeneration tissue and the second is refixation of the dislocated fragment and therefore a 1-stage reconstruction of the joint surface. It is important to also address concomitant injuries. Even though there is no consensus for a standardized or evidence-based therapy in literature, this article gives an overview of the diagnostics and available therapeutic options. PMID- 26148810 TI - Synchronization to a bouncing ball with a realistic motion trajectory. AB - Daily music experience involves synchronizing movements in time with a perceived periodic beat. It has been established for over a century that beat synchronization is less stable for the visual than for the auditory modality. This auditory advantage of beat synchronization gives rise to the hypotheses that the neural and evolutionary mechanisms underlying beat synchronization are modality-specific. Here, however, we found that synchronization to a periodically bouncing ball with a realistic motion trajectory was not less stable than synchronization to an auditory metronome. This finding challenges the auditory advantage of beat synchronization, and has important implications for the understanding of the biological substrates of beat synchronization. PMID- 26148809 TI - Pancreatic regeneration: basic research and gene regulation. AB - Pancreatic regeneration (PR) is an interesting phenomenon that could provide clues as to how the control of diabetes mellitus might be achieved. Due to the different regenerative abilities of the pancreas and liver, the molecular mechanism responsible for PR is largely unknown. In this review, we describe five representative murine models of PR and thirteen humoral mitogens that stimulate beta-cell proliferation. We also describe pancreatic ontogenesis, including the molecular transcriptional differences between alpha-cells and beta-cells. Furthermore, we review 14 murine models which carry defects in genes related to key transcription factors for pancreatic ontogenesis to gain further insight into pancreatic development. PMID- 26148811 TI - Acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis. AB - We report a case of acute hemorrhagic leukoencephalomyelitis in a man with viral myocarditis. A 48-year-old previously healthy male was found dead in his locked apartment. At autopsy he was found to be malnourished, and his lungs showed gross evidence of bilateral pneumonia with abscess formation and bullous emphysema. Multiple petechial hemorrhages were observed in the brain and mainly involved white matter in the cerebral hemispheres including the corpus callosum and internal capsule, as well as the cerebellum, brainstem, and spinal cord. Microscopy of the brain and spinal cord revealed perivenular hemorrhages, central microthrombi in venules with fibrin exudation into the subcortical white matter, and early perivenular demyelination associated with scanty mixed cellular infiltrates. Other microscopic features included widespread diffuse viral myocarditis, extensive suppurative bronchopneumonia, and chronic bronchitis. This case illustrates the death of a man with a rare fatal disease associated with two other potentially lethal diseases. The case also illustrates the importance of a holistic approach when determining the cause of death, especially when there are competing causes of death. PMID- 26148812 TI - Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. AB - Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments--especially for treatment-resistant depression (TRD)--are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research. PMID- 26148814 TI - Soft landing of bare PtRu nanoparticles for electrochemical reduction of oxygen. AB - Magnetron sputtering of two independent Pt and Ru targets coupled with inert gas aggregation in a modified commercial source has been combined with soft landing of mass-selected ions to prepare bare 4.5 nm diameter PtRu nanoparticles on glassy carbon electrodes with controlled size and morphology for electrochemical reduction of oxygen in solution. Employing atomic force microscopy (AFM) it is shown that the nanoparticles bind randomly to the glassy carbon electrode at a relatively low coverage of 7 * 10(4) ions MUm(-2) and that their average height is centered at 4.5 nm. Scanning transmission electron microscopy images obtained in the high-angle annular dark field mode (HAADF-STEM) further confirm that the soft-landed PtRu nanoparticles are uniform in size. Wide-area scans of the electrodes using X-ray photoelectron spectroscopy (XPS) reveal the presence of both Pt and Ru in atomic concentrations of ~9% and ~33%, respectively. Deconvolution of the high energy resolution XPS spectra in the Pt 4f and Ru 3d regions indicates the presence of both oxidized Pt and Ru. The substantially higher loading of Ru compared to Pt and enrichment of Pt at the surface of the nanoparticles is confirmed by wide-area analysis of the electrodes using time-of flight medium energy ion scattering (TOF-MEIS) employing both 80 keV He(+) and O(+) ions. The activity of electrodes containing 7 * 10(4) ions MUm(-2) of bare 4.5 nm PtRu nanoparticles toward the electrochemical reduction of oxygen was evaluated employing cyclic voltammetry (CV) in 0.1 M HClO4 and 0.5 M H2SO4 solutions. In both electrolytes a pronounced reduction peak was observed during O2 purging of the solution that was not evident during purging with Ar. Repeated electrochemical cycling of the electrodes revealed little evolution in the shape or position of the voltammograms indicating high stability of the nanoparticles supported on glassy carbon. The reproducibility of the nanoparticle synthesis and deposition was evaluated by employing the same experimental parameters to prepare nanoparticles on glassy carbon electrodes on three occasions separated by several days. Surfaces with almost identical electrochemical behavior were observed with CV, demonstrating the highly reproducible preparation of bare nanoparticles using physical synthesis in the gas-phase combined with soft landing of mass-selected ions. PMID- 26148813 TI - MAOA expression predicts vulnerability for alcohol use. AB - The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse. PMID- 26148815 TI - In vitro activity of synthetic tetrahydroindeno[2,1-c]quinolines on Leishmania mexicana. AB - New synthetic compounds based on tetrahydroindenoquinoline structure were evaluated for their in vitro antileishmanial activities. The seven compounds assayed have antiproliferative activities against promastigotes of Leishmania mexicana. Compound 1 and 3 were the most active (IC50 1.0 MUg/ml) and showed high selectivity towards the parasite. These compounds were selected to evaluate their effect on promastigote morphology and mitochondrial transmembrane potential as well as on the amastigote capability to survive into macrophages J774 cell line. Whereas compound 1 affected the promastigote cell cycle, compound 3 induced morphological changes and the total collapse of the mitochondrial transmembrane potential, a hallmark of apoptosis. Both compounds also affected the amastigote form of the parasite, decreasing their survival rate in J774 macrophages. Due to the greatest selectivity index, the apparent effect as apoptotic inducer and its sustained inhibition on intracellular amastigote replication, compound 3 is the best candidate to be tested in vivo. This compound is worth considering for the development of new antileishmanial drugs. PMID- 26148816 TI - Tandem repeat recombinant proteins as potential antigens for the sero-diagnosis of Schistosoma mansoni infection. AB - The diagnosis of schistosome infection, followed by effective treatment and/or mass drug administration, is crucial to reduce the disease burden. Suitable diagnostic tests and field-applicable tools are required to sustain schistosomiasis control programs. We therefore assessed the potential of tandem repeat (TR) proteins for sero-diagnosis of Schistosoma mansoni infection using an experimental mouse model. TR genes in the genome of S. mansoni were searched in silico and 7 candidates, named SmTR1, 3, 8, 9, 10, 11 and 15, were selected. Total RNA was extracted from S. mansoni adult worms and eggs. Target TR genes were amplified, cloned, and the proteins were expressed in Escherichia coli competent cells. Female BALB/c mice were infected with 100 S. mansoni cercariae and sera were collected each week post-infection for 18 weeks. The levels of IgG antibodies to SmTR antigens were compared to those to soluble egg antigen (SEA) and to soluble worm antigen preparation (SWAP). Sera of infected mice reacted to all the antigens whereas those of naive mice did not. IgG responses to SmTR1, 3, 9 and 10 were detected at the early stage of infection. Interestingly, antibodies reacting to SmTR3, 9, 10 and 15 dramatically decreased 4 weeks after treatment with praziquantel, while those against SEA and SWAP remained elevated. Our study suggests that TR proteins, especially SmTR10, may be suitable antigens for sero diagnosis of infection by S. mansoni and are potential markers for monitoring and surveillance of schistosomiasis, including re-infection after treatment with praziquantel. PMID- 26148817 TI - The Cell-CT 3-dimensional cell imaging technology platform enables the detection of lung cancer using the noninvasive LuCED sputum test. AB - The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5-year survival rate for lung cancer has changed little over the past 40 years. Early detection through emerging lung cancer screening programs promise the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Screening Trial reported that screening using 3 consecutive low-dose x-ray computed tomography scans provides a 20% reduction in lung cancer mortality compared with chest x-ray. However, this reduction in mortality comes with an unacceptable false-positive rate that increases patient risks and the overall cost of lung cancer screening. The LuCED test for detection of early lung cancer is reviewed in the current article. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell-CT, which images cells in 3 dimensions with submicron resolution. Algorithms are applied to the 3-dimensional cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification that could enable the cost-effective detection of lung cancer. PMID- 26148818 TI - Amoxicillin diminishes the thickness of the enamel matrix that is deposited during the secretory stage in rats. AB - BACKGROUND: The use of amoxicillin during early childhood has been associated with molar incisor hypomineralization. AIM: The objective of this study was to determine whether the use of amoxicillin interferes with enamel development, during secretion and early mineralization stages. DESIGN: Fifteen pregnant rats were randomly assigned to three groups that received physiological solution (sham group), 100 mg/kg/day amoxicillin (A100G), and 500 mg/kg/day amoxicillin (A500G). After birth, the pups in each group received the same treatment until post-natal day 7 or 12. The upper first molars were analyzed histomorphometrical and immunostaining with amelogenin on day 7, and MMP-20 on day 12 was performed using a semiquantitative method (H-score). RESULTS: At 7 days, several vacuolar structures were observed in the ameloblasts in the A100G and A500G groups. A significant reduction of the enamel thickness (P < 0.001) was found in amoxicillin-treated rats compared with the sham group. Significant differences were not observed in enamel thickness (P > 0.05) between the groups of 12-day-old rats. Moreover, significant differences were not observed in the number of amelogenin- and MMP-20-immunolabeled ameloblasts (P > 0.05) between groups. CONCLUSION: The present results suggest that amoxicillin interferes with the initial stages of amelogenesis by causing structural changes in the ameloblasts and a reduction of the enamel matrix. PMID- 26148819 TI - Longevity of the Subcutaneous Implantable Defibrillator: Long-Term Follow-Up of the European Regulatory Trial Cohort. AB - BACKGROUND: The recent advent of subcutaneous implantable cardioverter defibrillators (S-ICDs) has provided investigators with a safe and effective new therapy in patients at risk of sudden cardiac death. At present, no data are available with regard to the longevity of these new devices. This study evaluated the longevity of the S-ICD system. METHODS AND RESULTS: All patients enrolled in the European Regulatory Trial were included in the analysis. During follow-up, time and causes of device replacement or explantation were assessed and categorized. Device longevity was estimated using Kaplan-Meier analysis. Fifty five patients were followed for a median of 5.8 years. During follow-up, 26 (47%) patients underwent device replacement and 5 (9%) underwent device explantation. Median time to replacement was 5.0 years (Q1-Q3, 4.4-5.6 years). Replacement was caused by battery depletion in 25 patients (92%), of which 5 within 1.5 years because of premature battery depletion, and by infection in 1 patient (2%). Replacement for a transvenous ICD system was required in 4 patients (7%) because of ineffective defibrillation in 1 (0.003 per patient-year), need for resynchronization therapy in 2 (0.01 per patient-year), and for antibradycardia pacing in 1 (0.003 per patient-year). At 5 years follow-up, 71% of devices were still in service. CONCLUSIONS: This study provides the first estimate of S-ICD system longevity since its introduction in clinical practice. Median longevity of the first generation S-ICD system was 5.0 years. The majority of devices were replaced because of battery depletion. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01117792. PMID- 26148820 TI - Pulmonary alveolar proteinosis and clear cell renal cell carcinoma. PMID- 26148821 TI - Lifetime and 12-month prevalence, severity and unmet need for treatment of common mental disorders in Japan: results from the final dataset of World Mental Health Japan Survey. AB - BACKGROUND: The aim of this study is to estimate the lifetime and 12-month prevalence, severity and treatment of Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) mental disorders in Japan based on the final data set of the World Mental Health Japan Survey conducted in 2002-2006. METHODS: Face-to-face household interviews of 4130 respondents who were randomly selected from Japanese-speaking residents aged 20 years or older were conducted from 2002 to 2006 in 11 community populations in Japan (overall response rate, 56%). The World Mental Health version of the World Health Organization Composite International Diagnostic Interview (WMH-CIDI), a fully structured, lay administered psychiatric diagnostic interview, was used for diagnostic assessment. RESULTS: Lifetime/12-month prevalence of any DSM-IV common mental disorders in Japan was estimated to be 20.3/7.6%. Rank-order of four classes of mental disorders was anxiety disorders (8.1/4.9%), substance disorders (7.4/1.0%), mood disorders (6.5/2.3%) and impulse control disorders (2.0/0.7%). The most common individual disorders were alcohol abuse/dependence (7.3/0.9%), major depressive disorder (6.1/2.2%), specific phobia (3.4/2.3%) and generalized anxiety disorder (2.6/1.3%). While the lifetime prevalence of any mental disorder was greater for males and the middle-aged, the persistence (proportion of 12 month cases among lifetime cases) of any mental disorder was greater for females and younger respondents. Among those with any 12-month disorder, 15.3% were classified as severe, 44.1% moderate and 40.6% mild. Although a strong association between severity and service use was found, only 21.9% of respondents with any 12-month disorder sought treatment within the last 12 months; only 37.0% of severe cases received medical care. The mental health specialty sector was the most common resource used in Japan. Although the prevalence of mental disorders were quite low, mental disorders were the second most prevalent cause of severe role impairment among chronic physical and mental disorders. CONCLUSIONS: These results suggest lower prevalence of mental disorders in Japan than that in Western countries, although the general pattern of disorders, risk factors and unmet need for treatment were similar to those in other countries. Greater lifetime prevalence for males and greater persistence for females seems a unique feature of Japan, suggesting a cultural difference in gender-related etiology and course of disorders. The treatment rate in Japan was lower than that in most other high-income countries in WMH surveys. PMID- 26148822 TI - How to quantify the evidence for the absence of a correlation. AB - We present a suite of Bayes factor hypothesis tests that allow researchers to grade the decisiveness of the evidence that the data provide for the presence versus the absence of a correlation between two variables. For concreteness, we apply our methods to the recent work of Donnellan et al. (in press) who conducted nine replication studies with over 3,000 participants and failed to replicate the phenomenon that lonely people compensate for a lack of social warmth by taking warmer baths or showers. We show how the Bayes factor hypothesis test can quantify evidence in favor of the null hypothesis, and how the prior specification for the correlation coefficient can be used to define a broad range of tests that address complementary questions. Specifically, we show how the prior specification can be adjusted to create a two-sided test, a one-sided test, a sensitivity analysis, and a replication test. PMID- 26148823 TI - Validation of Italian rebus puzzles and compound remote associate problems. AB - Rebus puzzles and compound remote associate problems have been successfully used to study problem solving. These problems are physically compact, often can be solved within short time limits, and have unambiguous solutions, and English versions have been normed for solving rates and levels of difficulty. Many studies on problem solving with sudden insight have taken advantage of these features in paradigms that require many quick solutions (e.g., solution priming, visual hemifield presentations, electroencephalography, fMRI, and eyetracking). In order to promote this vein of research in Italy, as well, we created and tested Italian versions of both of these tests. The data collected across three studies yielded a pool of 88 rebus puzzles and 122 compound remote associate problems within a moderate range of difficulty. This article provides both sets of problems with their normative data, for use in future research. PMID- 26148824 TI - Mean centering helps alleviate "micro" but not "macro" multicollinearity. AB - There seems to be confusion among researchers regarding whether it is good practice to center variables at their means prior to calculating a product term to estimate an interaction in a multiple regression model. Many researchers use mean centered variables because they believe it's the thing to do or because reviewers ask them to, without quite understanding why. Adding to the confusion is the fact that there is also a perspective in the literature that mean centering does not reduce multicollinearity. In this article, we clarify the issues and reconcile the discrepancy. We distinguish between "micro" and "macro" definitions of multicollinearity and show how both sides of such a debate can be correct. To do so, we use proofs, an illustrative dataset, and a Monte Carlo simulation to show the precise effects of mean centering on both individual correlation coefficients as well as overall model indices. We hope to contribute to the literature by clarifying the issues, reconciling the two perspectives, and quelling the current confusion regarding whether and how mean centering can be a useful practice. PMID- 26148826 TI - Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms. AB - Alzheimer's disease (AD) is one of the prevalent neurological disorders of the central nervous system hallmarked by increased beta-amyloid (Abeta) deposition and ensuing learning and memory deficit. In the present study, the beneficial effect of naringenin on improvement of learning and memory was evaluated in an Alzheimer's disease rat model. The Abeta-injected rats showed a lower alternation score in Y-maze task, impairment of retention and recall capability in passive avoidance test, and lower correct choices and higher errors in radial arm maze (RAM) task as compared to sham group in addition to enhanced oxidative stress and apoptosis. Naringenin, but not a combination of naringenin and fulvestrant (an estrogenic receptor antagonist) significantly improved the performance of Abeta injected rats in passive avoidance and RAM tasks. Naringenin pretreatment of Abeta-injected rats also lowered hippocampal malondialdehyde (MDA) with no significant effect on nitrite and superoxide dismutase (SOD) activity in addition to lowering apoptosis. These results suggest naringenin pretreatment attenuates Abeta-induced impairment of learning and memory through mitigation of lipid peroxidation and apoptosis and its beneficial effect is somewhat mediated via estrogenic pathway. PMID- 26148825 TI - Genetic deletion and pharmacological inhibition of Akt1 isoform attenuates bladder cancer cell proliferation, motility and invasion. AB - Isoform specific expression, intracellular localization and function of Akt in bladder cancer are not known. In the current study, we identified Akt1, followed by Akt2 and Akt3 as the predominant Akt isoform in human T24 and UM-UC-3 metastatic bladder cancer cells. Whereas Akt1 is localized at the membrane, cytoplasm and nucleus, Akt2 is solely cytoplasmic and Akt3 is mostly localized in the nucleus in T24 cells. ShRNA-mediated Akt1 knockdown resulted in impaired T24 cell survival, proliferation, colony formation, migration and microinvasion. Whereas pharmacological inhibition of Akt1 resulted in impaired T24 and UM-UC-3 cell motility, viability and proliferation, effect of pharmacological inhibition by Akt2 inhibitor was limited to proliferation in T24, but not UM-UC-3 cells. Our data provide important clues on the therapeutic benefits of targeting Akt1 for bladder cancer therapy. PMID- 26148827 TI - Improvement in acute care surgery medical student education and clerkships: use of feedback and loop closure. AB - BACKGROUND: The unpredictable and sometimes chaotic environment present in acute care surgery services (trauma, burn, surgical critical care, and nontrauma emergency surgery) can cause high levels of anxiety and stress that could impact a medical students' experience during their third year of medical school surgical clerkship. This negative perception perhaps is a determinant influence in diverting talented students into other medical subspecialties. We sought out to objectively identify potential areas of improvement through direct feedback and implement programmatic changes to address these areas. We hypothesized that as the changes were made, students' perception of the rotation would improve. MATERIALS AND METHODS: Review of end of clerkship third year of medical school trauma burn surgery rotation evaluations and comments was performed for the 2010 2011 academic year. Trends in negative feedback were identified and categorized into five areas for improvement as follows: logistics, student expectations, communication, team integration, and feedback. A plan was designed and implemented for each category. Feedback on improvements to the rotation was monitored via surveys and during monthly end of rotation face-to-face student feedback sessions with the rotation faculty facilitator and surgery clerkship director. Data were compiled and reviewed. RESULTS: Perceptions of the rotation markedly improved within the first month of the changes and continued to improve over the study time frame (2011-2013) in all five categories. We also observed an increase in the number of students selecting a surgical residency in the National Resident Matching Program match from a low of 8% in 2009-2010 before any interventions to 25% after full implementation of the improvement measures in 2011-2012. CONCLUSIONS: A systematic approach using direct feedback from students to address service-specific issues improves perceptions of students on the educational value of a busy trauma-burn acute care surgery service and may have a positive influence on students considering surgical careers to pursue a surgical specialty. PMID- 26148828 TI - A novel pure component contribution algorithm (PCCA) for extracting components' contribution from severely overlapped signals; an application to UV spectrophotometric data. AB - A novel, simple and accurate algorithm capable of extracting the contribution of each component from a mixture signal where the components are completely overlapped was developed. It is based on the development of a coded function which eliminates the signal of interfering components using mean centering as a processing tool; finally the pure contribution of each component is extracted. The algorithm allows the determination of each component as a single one. It was validated by the use of simulated data set of three overlapped signals and tested against simulated random noise. Two fit values were developed and calculated for optimization, one to test that that the absorptivity values of the extracted spectra are within the confidence limits of the slope and the other is the correlation between the pure and extracted spectra. It has been successfully applied to real UV data of binary mixture of Ibuprofen and Paracetamol and ternary mixture of Amiloride hydrochloride, Atenolol and Hydrochlorothiazide in tablets and capsules, respectively. The results were compared to previously reported separation method and no significant difference was found regarding both accuracy and precision. PMID- 26148829 TI - Nephelauxetic effect and 4f radial integrals of Tm3+ in crystals. AB - Bonding and covalency parameters have been evaluated from the nephelauxetic ratios betak=Fk (crystal)/Fk (free ion), with k=2, 4, 6, for 24 halide and chalcogenide crystals containing Tm(3+) ions. The radial expectation values for 4f electrons 4f of Tm(3+) ion in certain complex oxides, fluorides, and a sulfide have been determined by means of experimental Slater parameter shifts DeltaFk relative to the Fk values for the free ion Tm IV. The 1f values derived in the dielectric screening model have been compared with those computed by different types of 4f wave functions as well as with other estimates. PMID- 26148830 TI - Assessment on third order non linearity and other optical analyses of L Asparagine Monohydrate single crystal: An efficient candidate for harmonic conversions. AB - Single crystal of l-Asparagine Monohydrate, an organic material has been successfully grown by slow evaporation solution growth technique at ambient condition. The lattice parameters and its strain of the grown crystal have been evaluated from powder X-ray diffraction and found that it belongs to orthorhombic crystal system. The polarizability has been measured by using the Clausius Mossotti relation. The crystalline perfection of grown single crystal has been examined by high resolution X-ray diffraction and its imperfection in the diffraction plane was clearly visible by recording topographical image of the plane. From the high resolution XRD, it confirms that the crystal contained high crystalline perfection. The optical behavior was analyzed by photoluminescence and birefringence methods. In the photoluminescence, a broad peak has been observed at 475 nm which suggest that it emits blue light. The decay tendency of the material has also been observed by calculating decay constant. The optical homogeneity has been determined by the dispersion pattern of the material. The two photon absorption coefficient was further calculated by Z-scan, which gives the information about the third order non linear optical behavior of the material. The value of two-photon absorption coefficient is 4.25 * 10(-12)m/W. The thermal parameters like thermal effusivity, thermal diffusivity, specific heat and thermal conductivity was obtained by using photopyroelectric technique. The ferroelectric behavior of the grown specimen was analyzed from PE (polarization VS electric field) loop. The loop suggests that the material was a nearly equivalent to ideal capacitor. PMID- 26148831 TI - Synthesis of new colori/fluorimetric chemosensor for selective sensing of biologically important Fe3+, Cu2+ and Zn2+ metal ions. AB - New Schiff base chemosensors (1 and 2) based on aryl ether amine were synthesized and demonstrated positional isomer and functional group dependent colori/fluorimetric sensing of Fe(3+), Cu(2+) and Zn(2+) at ppm level. Methoxy salicylaldehyde based chemosensor 1 exhibited selective colorimetric sensing of Fe(3+) whereas 2-hydroxy naphthaldehyde based chemosensor 2 showed selective disappearance of yellow color for Cu(2+) ions. Interestingly, both 1 and 2 exhibited a highly selective strong turn-on fluorescence for Zn(2+). The significance of COOH group in 1 and 2 for Zn(2+) turn-on fluorescence sensing has been confirmed by structure-property studies. Concentration dependent studies of 1 and 2 indicate that Fe(3+), Cu(2+) and Zn(2+) can be detected up to 10 MUM. The formation of 1:1 Zn(2+) and chemosensor (1 and 2) confirmed by NMR studies. High selectivity of 1 and 2 was demonstrated by interference studies in presence of different metal ions. PMID- 26148832 TI - Concurrent and prospective associations between bullying victimization and substance use among Australian adolescents. AB - BACKGROUND: Adolescence is a vulnerable time for both substance use and bullying involvement; however, there is limited research on substance use among adolescent victims of bullying. This study aimed to examine concurrent and prospective associations between bullying and substance use, differentiating between passive victims, bully-victims and 'pure' bullies. METHOD: Associations between bullying involvement and substance use at baseline and 24 months post-baseline were examined in a cohort of adolescents in Australia. Bullying victims were divided into passive-victims (those who get bullied and do not bully others) and bully victims (those who both get bullied and bully others). Perpetrators of bullying were divided into 'pure' bullies (those who bully others but do not get bullied), and bully-victims (as above). Outcomes examined were past six month use of alcohol (any drinking; risky drinking), tobacco, and cannabis. RESULTS: While there was no evidence of an association between bullying victimization and/or perpetration and substance use at baseline, there was evidence of an association between bullying and substance use 24 months post-baseline. Specifically, there was evidence of increased odds of risky drinking and cannabis use for the bully victim group. CONCLUSIONS: Bully-victim status at age 13 was associated with substance use at age 15, controlling for concurrent bullying involvement at age 15. Bully-victims are a particularly high-risk group that could benefit from targeted substance use preventive interventions. Reducing bullying is of great importance in reducing substance use and other harms among adolescents. PMID- 26148833 TI - Fixing flaws in science must be professionalized. PMID- 26148834 TI - Using a matrix-analytical approach to synthesizing evidence solved incompatibility problem in the hierarchy of evidence. AB - OBJECTIVES: The hierarchy of evidence presupposes linearity and additivity of effects, as well as commutativity of knowledge structures. It thereby implicitly assumes a classical theoretical model. STUDY DESIGN AND SETTING: This is an argumentative article that uses theoretical analysis based on pertinent literature and known facts to examine the standard view of methodology. RESULTS: We show that the assumptions of the hierarchical model are wrong. The knowledge structures gained by various types of studies are not sequentially indifferent, that is, do not commute. External validity and internal validity are at least partially incompatible concepts. Therefore, one needs a different theoretical structure, typical of quantum-type theories, to model this situation. The consequence of this situation is that the implicit assumptions of the hierarchical model are wrong, if generalized to the concept of evidence in total. CONCLUSION: The problem can be solved by using a matrix-analytical approach to synthesizing evidence. Here, research methods that produce different types of evidence that complement each other are synthesized to yield the full knowledge. We show by an example how this might work. We conclude that the hierarchical model should be complemented by a broader reasoning in methodology. PMID- 26148835 TI - Patella Fractures Prior to Total Knee Arthroplasty: Worse Outcomes but Equivalent Survivorship. AB - Distal femur and/or tibial plateau fractures adversely affect outcomes of TKA; however it is unknown if a previous patella fracture affects outcome. We reviewed 113 patients undergoing TKA with a previous patella fracture from 1990 to 2012. Component survival was compared to 19,641 patients undergoing TKA for osteoarthritis during the same period. The 15-year implant survivals following a previous patella fracture was 86%. There was no difference in implant survival compared to patients undergoing TKA for OA (P=0.31). Knee society scores significantly improved following TKA; however patients with a fracture had complications related to knee flexion. Patients undergoing primary TKA following a patella fracture have similar overall revision free survival compared to those undergoing TKA for OA at 15-years. PMID- 26148836 TI - Morphology of the Proximal Tibia at Different Levels of Bone Resection in Japanese Knees. AB - The purpose was to measure the morphology of the proximal tibia at different levels for consideration of tibial tray design and placement. The morphology was analysed in 51 knees at 10, 15, 20, and 25 mm below the centre of the lateral tibial plateau. Surface rotation was measured by fitting an ellipse on the resection surface. The anteroposterior (AP), mediolateral (ML), medial AP (MAP) and lateral AP (LAP) dimensions were also measured. The resection surface showed internal rotation of 22.9 degrees from the 10 mm level to the 25 mm level. More distally, the ML/AP and MAP/LAP ratios showed significant changes. Surgeons should pay attention to morphological changes for patients with gross tibial bone defects in primary and revision total knee arthroplasty. PMID- 26148837 TI - Hypoalbuminemia More Than Morbid Obesity is an Independent Predictor of Complications After Total Hip Arthroplasty. AB - Health care reform is directing clinical practice towards improving outcomes and minimizing complications. Preoperative identification of high-risk patients and modifiable risk factors present opportunity for clinical research. A total of 49,475 total hip arthroplasty patients were identified from National Surgical Quality Improvement Program between 2006 and 2013. We compared morbidly obese patients (BMI>=40 kg/m(2)) and non-morbidly obese patients (BMI 18.5-40 kg/m(2)). We also compared patients with hypoalbuminemia (serum albumin <3.5 g/dL) against those with normal albumin. Our study demonstrates that hypoalbuminemia is a significant risk factor for mortality and major morbidity among total hip arthroplasty patients, while morbid obesity was only associated with an increased risk of superficial surgical site infection. Impressively, hypoalbuminemia patients carried a 5.94-fold risk of 30-day mortality. PMID- 26148839 TI - Feeding habits of the speckled guitarfish Rhinobatos glaucostigma (Elasmobranchii: Rhinobatidae). AB - The stomachs of 464 speckled guitarfish Rhinobatos glaucostigma were sampled from the south-eastern Gulf of California (GC) to determine diet composition. Numerical indices and prey-specific index of relative importance ((%I)PSIR ) were used to determine the feeding strategy of the species. An analysis of similarity (ANOSIM) was used to determine differences in diet with respect to sex, season (dry or rainy) and maturity stages (immature or mature). The diversity and niche breadth (by sex, season and maturity) and a general trophic level were determined. The overall diet was dominated by shrimps ((%I)PSIR = 43.47), amphipods ((%I)PSIR = 18.89) and crabs ((%I)PSIR = 18.07). ANOSIM demonstrated differences in the diet by maturity and season, but not by sex. Rainy and dry season diets were dominated by shrimps and amphipods, respectively. Immature specimens fed mainly on amphipods, whereas mature fish preferred shrimps and crabs. Rhinobatos glaucostigma showed a narrow niche breadth with an intermediary trophic level (TL = 3.72) and can be considered as a secondary consumer in the soft-bottom demersal community of the south-east GC. Understanding the feeding habits and trophic level of R. glaucostigma is vital to help identify the segments of the population vulnerable to overfishing by artisanal and industrial fisheries, and to aid in conservation and management of this elasmobranch. PMID- 26148838 TI - Metal-Free Decarboxylative Cyclization/Ring Expansion: Construction of Five-, Six , and Seven-Membered Heterocycles from 2-Alkynyl Benzaldehydes and Cyclic Amino Acids. AB - A one pot synthesis of 1H-benzo[g]indoles, tetrahydrobenzo[h]quinolines, and naphtho[1,2-b]azepines from 2-alkynyl benzaldehydes and cyclic amino acids is reported. The salient feature of the strategy involves formation of three new bonds (one C-N and two C-C bonds) by a metal-free decarboxylation/cyclization/one carbon ring expansion sequence in one pot. PMID- 26148840 TI - Hyperbranched poly(glycidol)/poly(ethylene oxide) crosslinked hydrogel for tissue engineering scaffold using e-beams. AB - A microporous hydrogel scaffold was developed from hyperbranched poly(glycidol) (HPG) and poly(ethylene oxide) (PEO) using electron beam (e-beam) induced cross linking for tissue engineering applications. In this study, HPG was synthesized from glycidol using trimethylol propane as a core initiator and cross-linked hydrogels were made using 0, 10, 20, and 30% HPG with respect to PEO. The effects of %-HPG on the swelling ratio, cross-linking density, mechanical properties, morphology, degradation, and cytotoxicity of the hydrogel scaffolds were then investigated. Increasing the HPG content increased the pore size of the hydrogel scaffold, as well as the porosity, elongation at break, degree of degradation and swelling ratio. In contrast, the presence of HPG decreased the cross-linking density of the hydrogel. There was no significant difference in compressive modulus and tensile strength of all compositions. The pore size of hydrogel scaffolds could be easily tailored by controlling the content of HPG in the polymer blend. Evaluation of the cytotoxicity demonstrated that HPG/PEO hydrogel scaffold has potential for use as a matrix for cellular attachment and proliferation. These results indicate that cross-linked HPG/PEO hydrogel can function as a potential material for tissue engineering scaffolds. Moreover, a facile method to prepare hydrogel microporous scaffolds for tissue engineering by e-beam irradiation was developed. PMID- 26148841 TI - Excess Integrins Cause Lung Entrapment of Mesenchymal Stem Cells. AB - Mesenchymal stem cells (MSCs) are largely entrapped in the lungs after intravenous delivery. The underlying mechanisms have been poorly understood. Flow cytometry and Western blot analysis showed that the expression levels of many integrins such as beta1, alpha5, and alphaVbeta3 in MSCs increased markedly upon cultured expansion in 2D monolayers, whose ligands fibronectin and vitronectin were detected on the surface of vascular endothelial cells in the lungs by immunostaining and flow cytometry. Blockade of integrin beta1, integrin alpha5, or integrins alphaVbeta3 with functional blocking antibodies significantly decreased the amount of MSCs entrapped in the lungs following intravenous infusion as determined by real-time PCR and histological analysis; meanwhile, corresponding increases in the levels of circulating MSCs in the blood and MSCs homed to the ischemic myocardium and inflamed ear were found. Intriguingly, a short period of 3D spheroid culture of MSCs, which had been expanded for several passages in monolayers, substantially reduced the expression levels of many integrins and the number of MSCs entrapped in the lungs. Our results indicate that the excess expression and activation of integrins is a significant cause of lung entrapment of MSCs. PMID- 26148842 TI - Strong and Selective Anion Binding within the Central Cavity of Molecular Knots and Links. AB - A molecular pentafoil knot and doubly and triply entwined [2]catenanes based on circular Fe(II) double helicate scaffolds bind halide anions in their central cavities through electrostatic and CH...X(-) hydrogen-bonding interactions. The binding is up to (3.6 +/- 0.2) * 10(10) M(-1) in acetonitrile (for pentafoil knot [2.Cl](PF6)9), making these topologically complex host molecules some of the strongest synthetic noncovalent binders of halide anions measured to date, comparable in chloride ion affinity to silver salts. PMID- 26148843 TI - Marginal genetic effects estimation in family and twin studies using random effects models. AB - Random-effects models are often used in family-based genetic association studies to properly capture the within families relationships. In such models, the regression parameters have a conditional on the random effects interpretation and they measure, e.g., genetic effects for each family. Estimating parameters that can be used to make inferences at the population level is often more relevant than the family-specific effects, but not straightforward. This is mainly for two reasons: First the analysis of family data often requires high-dimensional random effects vectors to properly model the familial relationships, for instance when members with a different degree of relationship are considered, such as trios, mix of monozygotic and dizygotic twins, etc. The second complication is the biased sampling design, such as the multiple cases families design, which is often employed to enrich the sample with genetic information. For these reasons deriving parameters with the desired marginal interpretation can be challenging. In this work we consider the marginalized mixed-effects models, we discuss challenges in applying them in ascertained family data and propose penalized maximum likelihood methodology to stabilize the parameter estimation by using external information on the disease prevalence or heritability. The performance of our methodology is evaluated via simulation and is illustrated on data from Rheumatoid Arthritis patients, where we estimate the marginal effect of HLA DRB1*13 and shared epitope alleles across three different study designs and combine them using meta-analysis. PMID- 26148845 TI - [Huge lipomatous tumor in the adductor muscle]. AB - Deep-seated lipomatous tumors of the peripheral soft tissue of the extremities are uncommon. The majority represent atypical lipomatous tumors or well differentiated liposarcomas. On rare occasions benign adipocytic tumors, such as hibernoma may present as huge, deep-lying subfascial masses. As a consequence of the deep location and usually heterogeneous signal intensities in imaging, they are particularly at risk to be misinterpreted as liposarcomas on clinical grounds. Furthermore, the rarity and thus limited familiarity with the morphological appearance and spectrum still represent a pitfall for the histopathological assessment. PMID- 26148844 TI - Impact of particulate matter and ammonia on average daily weight gain, mortality and lung lesions in pigs. AB - The present study investigated the simultaneous influence of particulate matter (PM10) and ammonia (NH3) on performance, lung lesions and the presence of Mycoplasma hyopneumoniae (M. hyopneumoniae) in finishing pigs. A pig herd experiencing clinical problems of M. hyopneumoniae infections was selected. In total, 1095 finishing pigs of two replicates in eight compartments each were investigated during the entire finishing period (FP). Indoor PM10 and NH3 were measured at regular intervals during the FP with two Grimm spectrometers and two Graywolf Particle Counters (PM10) and an Innova photoacoustic gas monitor (NH3). Average daily weight gain (ADG) and mortality were calculated and associated with PM10 and NH3 during the FP. Nasal swabs (10 pigs/compartment) were collected one week prior to slaughter to detect DNA of M. hyopneumoniae with nested PCR (nPCR). The prevalence and extent of pneumonia lesions, and prevalence of fissures and pleurisy were examined at slaughter (29 weeks). The results from the nasal swabs and lung lesions were associated with PM10 and NH3 during the FP and the second half of the FP. In the univariable model, increasing PM10 concentrations resulted in a higher odds of pneumonia lesions (second half of the FP: OR=8.72; P=0.015), more severe pneumonia lesions (FP: P=0.04, second half of the FP: P=0.009), a higher odds of pleurisy lesions (FP: OR=20.91; P<0.001 and second half of the FP: OR=40.85; P<0.001) and a higher number of nPCR positive nasal samples (FP: OR=328.00; P=0.01 and second half of the FP: OR=185.49; P=0.02). Increasing NH3 concentrations in the univariable model resulted in a higher odds of pleurisy lesions (FP: OR=21.54; P=0.003) and a higher number of nPCR positive nasal samples (FP: OR=70.39; P=0.049; second half of the FP: OR=8275.05; P=0.01). In the multivariable model, an increasing PM10 concentration resulted in a higher odds of pleurisy lesions (FP: OR=8.85; P=0.049). These findings indicate that the respiratory health of finishing pigs was significantly affected by PM10. PMID- 26148846 TI - Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells. AB - BACKGROUND: Bergapten (5-methoxypsoralen), a natural psoralen derivative present in many fruits and vegetables, has shown antitumoral effects in a variety of cell types. In this study, it has been addressed how Bergapten in breast cancer cells induces autophagic process. RESULTS: In MCF7 and ZR-75 breast cancer cells Bergapten exhibited anti-survival response by inducing the autophagic process increasing Beclin1, PI3KIII, UVRAG, AMBRA expression and conversion of LC3-I to LC3-II. LC3-GFP, Acridine orange assay and transmission electron microscopy even confirmed the increased autophagosome formations in treated cells. Bergapten induced autophagy is dependent by PTEN up-regulation, since silencing this gene, the induction of Beclin1 and the p-AKT/p-mTOR signal down-regulation were reversed. PTEN is transcriptionally regulated by Bergapten through the involvement of p38MAPK/NF-Y, as evidenced by the use of p38MAPK inhibitor SB203580, site-direct mutagenesis of NF-Y element and NF-Y siRNA. Furthermore NF Y knockdown prevented Bergapten-induced acid vesicular organelle accumulations (AVOs), strengthening the role of this element in mediating autophagy. CONCLUSIONS: Our data indicate PTEN as a key target of Bergapten action in breast cancer cells for the induction of autophagy. These findings add further details on the mechanism of action of Bergapten, therefore suggesting that phytochemical compounds may be implemented in the novel strategies for breast cancer treatment. PMID- 26148847 TI - Dynamic transcriptome analysis and volatile profiling of Gossypium hirsutum in response to the cotton bollworm Helicoverpa armigera. AB - In response to insect herbivory, plants emit elevated levels of volatile organic compounds for direct and indirect resistance. However, little is known about the molecular and genomic basis of defense response that insect herbivory trigger in cotton plants and how defense mechanisms are orchestrated in the context of other biological processes. Here we monitored the transcriptome changes and volatile characteristics of cotton plants in response to cotton bollworm (CBW; Helicoverpa armigera) larvae infestation. Analysis of samples revealed that 1,969 transcripts were differentially expressed (log2|Ratio| >= 2; q <= 0.05) after CBW infestation. Cluster analysis identified several distinct temporal patterns of transcriptome changes. Among CBW-induced genes, those associated with indirect defense and jasmonic acid pathway were clearly over-represented, indicating that these genes play important roles in CBW-induced defenses. The gas chromatography mass spectrometry (GC-MS) analyses revealed that CBW infestation could induce cotton plants to release volatile compounds comprised lipoxygenase-derived green leaf volatiles and a number of terpenoid volatiles. Responding to CBW larvae infestation, cotton plants undergo drastic reprogramming of the transcriptome and the volatile profile. The present results increase our knowledge about insect herbivory-induced metabolic and biochemical processes in plants, which may help improve future studies on genes governing processes. PMID- 26148849 TI - The epidemiological changes of HCV and HBV infections in the era of new antiviral therapies and the anti-HBV vaccine. AB - The World Health Organization (WHO) resolution adopted in 2010 recognized viral hepatitis as a global health problem. In April 2014, for the first time, the WHO produced guidelines for the screening, care and treatment of persons with hepatitis C infections. In May 2014, a follow-up resolution urged WHO Member States to develop and implement a national strategy for the prevention, diagnosis and treatment of viral hepatitis based on the local epidemiological context. Although blood donor screening, which began in the early 1990s, has reduced the spread of the virus in the population, the WHO estimates that 150 million people are chronically infected with hepatitis C virus (HCV) and are at an increased risk of developing liver cirrhosis and hepatocellular carcinoma. In addition, 3-4 million people are infected each year. HCV treatment is currently evolving rapidly, and several drugs are in various stages of development. With regard to the hepatitis B virus (HBV), in March 2015, the WHO published the first guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection, which were designed to complement the recent guidelines on HCV. Although the introduction of an effective vaccine against the hepatitis B virus has reduced the prevalence and health and economic impact of hepatitis in industrialized countries, the WHO estimates that more than 2 billion people are HBV-infected and 350 million people are chronic carriers. PMID- 26148848 TI - Epigenetic Modulation of Microglial Inflammatory Gene Loci in Helminth-Induced Immune Suppression: Implications for Immune Regulation in Neurocysticercosis. AB - In neurocysticercosis, parasite-induced immune suppressive effects are thought to play an important role in enabling site-specific inhibition of inflammatory responses to infections. It is axiomatic that microglia-mediated (M1 proinflammatory) response causes central nervous system inflammation; however, the mechanisms by which helminth parasites modulate microglia activation remain poorly understood. Here, we show that microglia display a diminished expression of M1-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide synthase 2 (NOS2) in murine neurocysticercosis. Microglia also exhibited a lack of myeloid cell maturation marker major histocompatibility complex (MHC)-II in these parasite-infected brains. Treatment of microglia with helminth soluble/secreted factors (HSFs) in vitro did not induce expression of M1-inflammatory signature molecule NOS2 as well as MHC-II in primary microglia. However, HSF treatment completely inhibited lipopolysaccharide-induced increase in expression of MHC-II, NOS2 and nitric oxide production in these cells. As epigenetic modulation of chromatin states that regulates recruitment of RNA polymerase II (Pol-II) is a key regulatory step in determining gene expression and functional outcome, we next evaluated whether HSF induced modulation of these phenomenon in microglia in vitro. Indeed, HSF downregulated Pol-II recruitment to the promoter region of TNF-alpha, IL-6, NOS2, MHC-II, and transcription factor CIITA (a regulator of MHC-II expression), by itself. Moreover, HSF suppressed the lipopolysaccharide-induced increase in Pol II recruitment as well. In addition, HSF exposure reduced the positive histone marks H3K4Me3 and H3K9/14Ac at the promoter of TNF-alpha, IL-6, NOS2, MHC-II, and CIITA. These studies provide a novel mechanistic insight into helminth-mediated immune suppression in microglia via modulation of epigenetic processes. PMID- 26148851 TI - Breast abscess and sepsis arising from oral infection. PMID- 26148850 TI - Structural Barriers to Antiretroviral Therapy Among Sex Workers Living with HIV: Findings of a Longitudinal Study in Vancouver, Canada. AB - In light of limited data on structural determinants of access and retention in antiretroviral therapy (ART) among sex workers, we examined structural correlates of ART use among sex workers living with HIV over time. Longitudinal data were drawn from a cohort of 646 female sex workers in Vancouver, Canada (2010-2012) and linked pharmacy records on ART dispensation. We used logistic regression with generalized estimating equations (GEE) to examine correlates of gaps in ART use (i.e., treatment interruptions or delayed ART initiation), among HIV seropositive participants (n = 74). Over a 2.5-year period, 37.8 % of participants experienced gaps in ART use (i.e., no ART dispensed in a 6-month period). In a multivariable GEE model, younger age, migration/mobility, incarceration, and non-injection drug use independently correlated with gaps in ART use. In spite of successes scaling up ART in British Columbia, younger, mobile, or incarcerated sex workers face persistent gaps in access and retention irrespective of drug use. Community based, tailored interventions to scale-up entry and retention in ART for sex workers should be further explored in this setting. PMID- 26148852 TI - Parasite management extension - challenging traditional practice through adoption of a systems approach. AB - The drivers for anthelmintic use today are substantial and anthelmintic use has become an embedded normalised behaviour. The cheapness and easy availability of anthelmintic products has meant that New Zealand farmers have had access to easy "solutions" for dealing with parasites and minimal forward planning or system redesign has been required. Despite 30 years of messaging about the emerging issue of anthelmintic resistance, management to reduce parasitism and the need to change behaviour, farmer practice has largely remained unchanged. Traditional approaches to extension, particularly around parasite management, appear to have been quite ineffective, apart from encouraging change in anthelmintic products and a switch to use of anthelmintics in combination. More effective approaches are required. The evolving nature of anthelmintic resistance and sustainable management of parasitism require attitudes, knowledge and behaviour to change. This is a challenge for all players in the industry; researchers, manufacturers and sellers, advisors and farmers. Looking beyond agriculture to the health sector provides some insight into models of decision making and behaviour change that can inform future strategies. Features in the health belief model including concepts of self-efficacy and cues to action appear to align with the issues, challenges and culture prevailing in farming, and parasite management in particular. Programmes through which farmers have made substantial beneficial behaviour change and the lessons learnt are discussed. Effecting consistent behaviour change around parasite management will involve new approaches by all participants in the process. And the process itself also needs to change. It requires an understanding of whole-farm systems, and the consideration of all the sources of influence on the farmer and the other participants in the process. The process of knowledge sharing involving the farmer should be based on equality; each person in the process brings their own expertise and knowledge and that needs to be valued and integrated into new practices. In effect, a multi disciplinary team approach is required through which knowledge is shared and developed, confidence and understanding is developed, practice and behaviour is reflected on and positive behaviours are given affirmation. PMID- 26148854 TI - Neurological damage arising from intrapartum hypoxia/acidosis. AB - Complications occurring at any level of foetal oxygen supply will result in hypoxaemia, and this may ultimately lead to hypoxia/acidosis and neurological damage. Hypoxic-ischaemic encephalopathy (HIE) is the short-term neurological dysfunction caused by intrapartum hypoxia/acidosis, and this diagnosis requires the presence of a number of findings, including the confirmation of newborn metabolic acidosis, low Apgar scores, early imaging evidence of cerebral oedema and the appearance of clinical signs of neurological dysfunction in the first 48 h of life. Cerebral palsy (CP) consists of a heterogeneous group of nonprogressive movement and posture disorders, frequently accompanied by cognitive and sensory impairments, epilepsy, nutritional deficiencies and secondary musculoskeletal lesions. Although CP is the most common long-term neurological complication associated with intrapartum hypoxia/acidosis, >80% of cases are caused by other phenomena. Data on minor long-term neurological deficits are scarce, but they suggest that less serious intellectual and motor impairments may result from intrapartum hypoxia/acidosis. This chapter focuses on the existing evidence of neurological damage associated with poor foetal oxygenation during labour. PMID- 26148853 TI - Sodium hyaluronate and chondroitin sulfate replenishment therapy can improve nocturia in men with post-radiation cystitis: results of a prospective pilot study. AB - BACKGROUND: Radiotherapy is one of the treatment options for prostate cancer (PCa) but up to 25% of men report about severe nocturia (nocturnal voiding). The combination of hyaluronic acid (HA) and chondroitin sulfate (CS) resembles glycosaminoglycan (GAG) replenishment therapy. The aim of our study was to evaluate the impact of HA and CS on nocturia, in men with nocturia after PCa radiotherapy. METHODS: Twenty-three consecutive patients with symptomatic cystitis after external radiotherapy for PCa were enrolled. Patients underwent bladder instillation therapy with HA and CS weekly for the first month and, afterwards, on week 6, 8 and 12. Nocturnal voiding frequency was assessed by item 3 (Q3) of the Interstitial Cystitis Symptoms Index (ICSI) and item 2 (Q2) of the Interstitial Cystitis Problem Index (ICPI). Data were analyzed with paired samples T-test and adjusted for age. RESULTS: Eighteen patients (78%) reported about nocturia. Pre- and post-treatment ICSI-Q3 was 2.13 +/- 0.28 and 1.61 +/- 0.21 (-24.4%, p = 0.001). With logistic regression analysis, both age and baseline ICSI-Q3 had a significant impact on nocturnal voiding frequency (r = 0.293, p = 0.011 and r = 0.970, p < 0.001). Pre- and post-treatment ICPI-Q2 was 1.87 +/- 0.26 and 1.30 +/- 0.25 (-30.5%, p = 0.016); logistic regression analysis was without significant findings. CONCLUSION: Bladder instillation treatment with a combination of HA and CS was effective in reducing nocturnal voiding frequency in men with post-radiation bladder pain for PCa. Randomized, controlled trials with sham treatment are needed to confirm our result. PMID- 26148855 TI - Complement factor I from flatfish half-smooth tongue (Cynoglossus semilaevis) exhibited anti-microbial activities. AB - Complement factor I (Cfi) is a soluble serine protease which plays a crucial role in the modulation of complement cascades. In the presence of substrate modulating cofactors (such as complement factor H, C4bp, CR1, etc), Cfi cleaves and inactivates C3b and C4b, thereby controlling the complement-mediated processes. In this study, we sequenced and characterized Cfi gene from Cynoglossus Semilaevis (designated as CsCfi) for the first time. The full-length cDNA of CsCfi was 2230 bp in length, including a 98 bp 5'-untranslated region (UTR), a 164 bp 3'-UTR and a 1968 bp open reading frame (ORF). It encoded a polypeptide of 656 amino acids, with a molecular mass of 72.28 kDa and an isoelectric point of 7.71. A signal peptide was defined at N-terminus, resulting in a 626-residue mature protein. Multiple sequence alignment revealed that Cfi proteins were well conserved with the typical modular architecture and identical active sites throughout the vertebrates, which suggested the conserved function of Cfi. Phylogenetic analysis indicated that CsCfi and the homologous Cfi sequences from teleosts clustered into a clade, separating from another clade from the cartilaginous fish and other vertebrates. Tissue expression profile analysis by quantitative real-time PCR (qRT-PCR) showed that CsCfi mRNA constitutively expressed in all tested tissues, with the predominant expression in liver and the lowest in stomach. Temporal expression levels of CsCfi after challenging with Vibrio anguillarum showed different expression patterns in intestine, spleen, skin, blood, head kidney and liver. The recombinant CsCfi (rCsCfi) protein showed broad-spectrum antimicrobial activities against the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and Shewanella putrefaciens. The research revealed that CsCfi plays an important role in C. Semilaevis immunity. PMID- 26148856 TI - The Pharmacological and Physiological Role of Multidrug-Resistant Protein 4. AB - Multidrug-resistant protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is distributed in a variety of tissues and a number of cancers. As a drug transporter, MRP4 is responsible for the pharmacokinetics and pharmacodynamics of numerous drugs, especially antiviral drugs, antitumor drugs, and diuretics. In this regard, the functional role of MRP4 is affected by a number of factors, such as genetic mutations; tissue-specific transcriptional regulations; post-transcriptional regulations, including miRNAs and membrane internalization; and substrate competition. Unlike other C family members, MRP4 is in a pivotal position to transport cellular signaling molecules, through which it is tightly connected to the living activity and physiologic processes of cells and bodies. In the context of several cancers in which MRP4 is overexpressed, MRP4 inhibition shows striking effects against cancer progression and drug resistance. In this review, we describe the role of MRP4 more specifically in both healthy conditions and disease states, with an emphasis on its potential as a drug target. PMID- 26148857 TI - The Inhibitor Ko143 Is Not Specific for ABCG2. AB - Imaging ATP-binding cassette (ABC) transporter activity in vivo with positron emission tomography requires both a substrate and a transporter inhibitor. However, for ABCG2, there is no inhibitor proven to be specific to that transporter alone at the blood-brain barrier. Ko143 [[(3S,6S,12aS) 1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4 dioxopyrazino[1',2':1,6]pyrido[3,4- b]indole-3-propanoic acid 1,1-dimethylethyl ester], a nontoxic analog of fungal toxin fumitremorgin C, is a potent inhibitor of ABCG2, although its specificity in mouse and human systems is unclear. This study examined the selectivity of Ko143 using human embryonic kidney cell lines transfected with ABCG2, ABCB1, or ABCC1 in several in vitro assays. The stability of Ko143 in rat plasma was measured using high performance liquid chromatography. Our results show that, in addition to being a potent inhibitor of ABCG2, at higher concentrations (>=1 MUM) Ko143 also has an effect on the transport activity of both ABCB1 and ABCC1. Furthermore, Ko143 was found to be unstable in rat plasma. These findings indicate that Ko143 lacks specificity for ABCG2 and this should be taken into consideration when using Ko143 for both in vitro and in vivo experiments. PMID- 26148858 TI - Nanosecond pulsed electric field inhibits proliferation and induces apoptosis in human osteosarcoma. AB - OBJECTIVE: Recent studies suggest that nanosecond pulsed electric field (nsPEF) is a novel minimal invasive and non-thermal ablation method that can induce apoptosis in different solid tumors. But the efficacy of nsPEF on bone-related tumors or bone metastasis is kept unknown. The current study investigates antitumor effect of nsPEF on osteosarcoma MG-63 cells in vitro. METHOD: MG-63 cells were treated with nsPEF with different electric field strengths (0, 10, 20, 30, 40, and 50 kV/cm) and different pulse numbers (0, 6, 12, 18, 24, and 30 pulses). The inhibitory effect of nsPEF on the growth of MG-63 cells was measured by Cell Counting Kit-8 (CCK-8) assay at different time points (0, 3, 12, 24, and 48 h post nsPEF treatment). The apoptosis was analyzed by Hoechst stain, in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and flow cytometric analysis. The expression of osteoprotegerin (OPG), receptor activator of NF-kappaB ligand (RANKL), and tumor necrosis factor alpha (TNF-alpha) was examined by reverse-transcription polymerase chain reaction (RT PCR) and western blot. RESULTS: The CCK-8 assay showed that nsPEF induced a distinct electric field strength- and pulse number-dependent reduction of cell proliferation. For treatment parameter optimizing, the condition 40 kV/cm and 30 pulses at 24 h post nsPEF achieved the most significant apoptotic induction rate. Hoechst, TUNEL, and flow cytometric analysis showed that the cell apoptosis was induced and cells were arrested in the G0/G1 phase. PCR and western blot analysis demonstrated that nsPEF up-regulated OPG expression had no effect on RANKL, increased OPG/RANKL ratio. CONCLUSION: NsPEF inhibits osteosarcoma growth, induces apoptosis, and affects bone metabolism by up-regulating OPG, indicating nsPEF-induced apoptosis in osteosarcoma MG-63 cells. NsPEF has potential to treat osteosarcoma or bone metastasis. When nsPEF is applied on metastatic bone tumors, it might be beneficial by inducing osteoblastic differentiation without cancer proliferation. In the future, nsPEF might be one of the treatments of metastatic bone tumor. PMID- 26148859 TI - Illicit Internet availability of drugs subject to recall and patient safety consequences. AB - BACKGROUND: Permanently recalled drugs are a public health concern if they remain accessible in violation of applicable regulation. Illicit online pharmacies act as an alternative form of access and have been associated with the sale to patients of counterfeit/falsified/fraudulent/substandard drugs. We wished to determine if permanently recalled and significantly restricted drugs were illegally marketed for sale online. OBJECTIVE: The study was conducted in two phases with two objectives. The first phase attempted to identify drugs subject to permanent recall in certain major pharmaceutical markets as well as those listed as recalled or significantly restricted by the United Nations. We also examined the market authorization status of identified drugs in China and India. The second phase used structured searches on the Internet to determine if identified drugs were marketed for sale online. SETTING: The World Wide Web. METHOD: After identification of permanently recalled and restricted drugs we conducted Internet searches for illegal "no prescription" marketing events. We assessed the form of marketing, whether a site offered direct-to-patient sale, use of social media marketing, and the site's compliance status with external monitoring bodies. MAIN OUTCOME: Number of recalled drugs marketed as available for purchase on the Internet. RESULTS: We identified 16 class I equivalent permanently recalled or restricted drugs, 56.3 % (n = 9) of which maintained market authorization in either China or India. Half (n = 8) were marketed for sale online without a prescription direct-to-patient. Use of social media marketing was mixed, with only 18.8 % (n = 3) of recalled drugs having a presence on Facebook, though 50.0 % (n = 8) had content on Twitter. We also found the majority (68.8 %, n = 11) were available and marketed for sale by vendors on the wholesale/business-to-business website alibaba.com primarily as active pharmaceutical ingredient. CONCLUSION: Despite efforts in several countries to restrict access to these drugs or permanently remove them from the market, our study indicates that various sources actively market recalled drugs for sale online. Drug regulators, public health agencies, and law enforcement officials should act with urgency to appropriately restrict and regulate these sales to protect global patients and consumers. PMID- 26148860 TI - Pharmacists performing quality spirometry testing: an evidence based review. AB - BACKGROUND: The scope of pharmacist services for patients with pulmonary disease has primarily focused on drug related outcomes; however pharmacists have the ability to broaden the scope of clinical services by performing diagnostic testing including quality spirometry testing. Studies have demonstrated that pharmacists can perform quality spirometry testing based upon international guidelines. AIM OF THE REVIEW: The primary aim of this review was to assess the published evidence of pharmacists performing quality spirometry testing based upon American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. In order to accomplish this, the description of evidence and type of outcome from these services were reviewed. METHODS: A literature search was conducted using five databases [PubMed (1946-January 2015), International Pharmaceutical Abstracts (1970 to January 2015), Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews] with search terms including pharmacy, spirometry, pulmonary function, asthma or COPD was conducted. Searches were limited to publications in English and reported in humans. In addition, Uniform Resource Locators and Google Scholar searches were implemented to include any additional supplemental information. RESULTS: Eight studies (six prospective multi-center trials, two retrospective single center studies) were included. Pharmacists in all studies received specialized training in performing spirometry testing. Of the eight studies meeting inclusion and exclusion criteria, 8 (100%) demonstrated acceptable repeatability of spirometry testing based upon standards set by the ATS/ERS guidelines. Acceptable repeatability of seven studies ranged from 70 to 99% consistent with published data. CONCLUSION: Available evidence suggests that quality spirometry testing can be performed by pharmacists. More prospective studies are needed to add to the current evidence of quality spirometry testing performed by pharmacists and to measure health outcomes of the pulmonary patient. PMID- 26148861 TI - PD-L1 expression in small cell lung cancer. PMID- 26148862 TI - Ionothermal synthesis, crystal structure, topology and catalytic properties of heterometallic coordination polymers constructed from N-(phosphonomethyl) iminodiacetic acid. AB - Reactions of rare earth chlorides, N-(phosphonomethyl)iminodiacetic acid (H(4)pmida) and ferrous oxalate dihydrate under ionothermal conditions result in four new isostructural 3d-4f heterometal coordination polymers, [LnFe(III)Fe(6)(Hpmida)(6)].2H(2)O {Ln = Eu (1), Dy (2), Ho (3) and Y (4)}. All compounds were characterized by infrared spectroscopy, elemental analysis, thermogravimetric analysis, and X-ray diffraction. The compounds feature a very interesting three dimensional (3-D) structure built up from a secondary building unit, [Fe(2)(Hpmida)(2)](2-) and possess a new topology type and complicated unique tilings. The catalytic properties of compounds 1-4 were investigated showing that these types of compounds are heterogeneous catalysts in the Knoevenagel condensation with high selectivity. PMID- 26148863 TI - Corrigendum. PMID- 26148864 TI - The phenomenon of co-morbid physical and mental illness in acute medical care: the lived experience of Australian health professionals. AB - BACKGROUND: An estimated 30-50% of patients admitted to acute medical care settings experience co-morbid physical and mental illness. Research suggests that health professionals in these settings find managing this patient group challenging. A number of studies have investigated health professional's attitudes and perceptions however there is limited research that investigates the lived experience in a current Australian healthcare context. The aim of this study was to explicate an in-depth description of the health professional's experience when caring for patients experiencing co-morbid physical and mental illness in Australian acute medical care settings. METHODS: A phenomenological design was undertaken with six participants representing nursing and medical disciplines. In 2013-2014 one-on-one semi-structured interviews were used and the data collected underwent thematic analysis using an extended version of Colaizzi's phenomenological inquiry. RESULTS: Six themes emerged including challenging behaviours, environmental and organisational factors, lack of skills, knowledge and experience, hyper-vigilance and anxiety, duty of care and negative attitudes with an overarching theme of fear of the unknown. CONCLUSIONS: Staff in acute medical care settings were unsure of patients with mental illness and described them as unpredictable, identifying that they lacked requisite mental health literacy. Regular training is advocated. PMID- 26148865 TI - Imaging dose from cone beam computed tomography in radiation therapy. AB - Imaging dose in radiation therapy has traditionally been ignored due to its low magnitude and frequency in comparison to therapeutic dose used to treat patients. The advent of modern, volumetric, imaging modalities, often as an integral part of linear accelerators, has facilitated the implementation of image-guided radiation therapy (IGRT), which is often accomplished by daily imaging of patients. Daily imaging results in additional dose delivered to patient that warrants new attention be given to imaging dose. This review summarizes the imaging dose delivered to patients as the result of cone beam computed tomography (CBCT) imaging performed in radiation therapy using current methods and equipment. This review also summarizes methods to calculate the imaging dose, including the use of Monte Carlo (MC) and treatment planning systems (TPS). Peripheral dose from CBCT imaging, dose reduction methods, the use of effective dose in describing imaging dose, and the measurement of CT dose index (CTDI) in CBCT systems are also reviewed. PMID- 26148866 TI - Quality and dose optimization in hand computed radiography. AB - The objective of the present study was to optimize a radiographic technique for hand examinations using a computed radiography (CR) system and demonstrate the potential for dose reductions compared with clinically established technique. An exposure index was generated from the optimized technique to guide operators when imaging hands. Homogeneous and anthropomorphic phantoms that simulated a patient's hand were imaged using a CR system at various tube voltages and current settings (40-55 kVp, 1.25-2.8 mAs), including those used in clinical routines (50 kVp, 2.0 mAs) to obtain an optimized chart. The homogeneous phantom was used to assess objective parameters that are associated with image quality, including the signal difference-to-noise ratio (SdNR), which is used to define a figure of merit (FOM) in the optimization process. The anthropomorphic phantom was used to subjectively evaluate image quality using Visual Grading Analysis (VGA) that was performed by three experienced radiologists. The technique that had the best VGA score and highest FOM was considered the gold standard (GS) in the present study. Image quality, dose and the exposure index that are currently used in the clinical routine for hand examinations in our institution were compared with the GS technique. The effective dose reduction was 67.0%. Good image quality was obtained for both techniques, although the exposure indices were 1.60 and 2.39 for the GS and clinical routine, respectively. PMID- 26148867 TI - Reporting on the temporal properties of visual events masked with continuous flash suppression. AB - To what extent can individuals introspect on dynamic properties of masked stimuli? Specifically, can observers report about the order in which a visual stimulus occurs, relative to a behavior, even when that stimulus is dramatically reduced in visibility via masking? Masking stimuli using continuous flash suppression, we asked participants to report on whether the stimulus appeared before or after a button-press. Data collected across three studies are consistent with the notion that information on the temporal order of events is preserved even when the visibility of the event in question is impoverished. These data may suggest that dynamic properties of masked stimuli are a promising set of features for understanding questions regarding an observer's perceptual experience and limitations of high-level information processing. PMID- 26148868 TI - Distinguishing nuclei-specific benzo[a]pyrene-induced effects from whole-cell alterations in MCF-7 cells using Fourier-transform infrared spectroscopy. AB - Exposure to chemicals such as benzo[a]pyrene (B[a]P) can generate intracellular toxic mechanisms. Fourier-transform infrared (FTIR) spectroscopy is a novel approach that allows the non-destructive analysis of underlying chemical bond alterations in patho-physiological processes. This study set out to examine whether B[a]P-induced whole cell alterations could be distinguished from effects on nuclei of exposed cells. Using attenuated total reflection FTIR (ATR-FTIR) spectroscopy, alterations in nuclei isolated from B[a]P-treated MCF-7 cells concentrated either in G0/G1- or S-phase were observed. B[a]P-induced effects in whole-cells included alterations to lipids, DNA and protein spectral regions. Absorbance areas for protein and DNA/RNA regions in B[a]P-treated whole cells differed significantly (P<0.0001) from vehicle controls and these observations correlated with alterations noted in isolated nuclei. Our findings provide evidence that FTIR spectroscopy has the ability to identify specific chemical induced alterations. PMID- 26148869 TI - Tumor characterization and stratification by integrated molecular profiles reveals essential pan-cancer features. AB - BACKGROUND: Identification of tumor heterogeneity and genomic similarities across different cancer types is essential to the design of effective stratified treatments and for the discovery of treatments that can be extended to different types of tumors. However, systematic investigations on comprehensive molecular profiles have not been fully explored to achieve this goal. RESULTS: Here, we performed a network-based integrative pan-cancer genomic analysis on >3000 samples from 12 cancer types to uncover novel stratifications among tumors. Our study not only revealed recurrently reported cross-cancer similarities, but also identified novel ones. The macro-scale stratification demonstrates strong clinical relevance and reveals consistent risk tendency among cancer types. The micro-scale stratification shows essential pan-cancer heterogeneity with subgroup specific gene network characteristics and biological functions. CONCLUSIONS: In summary, our comprehensive network-based pan-cancer stratification provides valuable information about inter- and intra- cancer stratification for patient clinical assessments and therapeutic strategies. PMID- 26148870 TI - Axillary conservation in early breast cancer. PMID- 26148871 TI - miR-125a-3p and miR-483-5p promote adipogenesis via suppressing the RhoA/ROCK1/ERK1/2 pathway in multiple symmetric lipomatosis. AB - Multiple symmetric lipomatosis (MSL) is a rare disease characterized by symmetric and abnormal distribution of subcutaneous adipose tissue (SAT); however, the etiology is largely unknown. We report here that miR-125a-3p and miR-483-5p are upregulated in the SAT of MSL patients, promoting adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway. TaqMan microRNA (miR) array analysis revealed that 18 miRs were upregulated in the SAT of MSL patients. Transfection of human adipose-derived mesenchymal stem cells (hADSCs) with the individual agomirs of these 18 miRs showed that miR-125a-3p and miR-483-5p significantly promoted adipogenesis. A dual-luciferase assay showed that RhoA and ERK1 were the targets of miR-125a-3p and miR-483-5p, respectively. Moreover, transfection of hADSCs with mimics of miR-125a-3p and miR-483-5p resulted in a pronounced decrease of ERK1/2 phosphorylation in the nucleus; conversely, transfection of hADSCs with inhibitors of miR-125a-3p and miR-483-5p led to a significant increase of ERK1/2 phosphorylation in the nucleus. Most importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice. These results demonstrated that miR-125a-3p and miR-483-5p coordinately promoted adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway. Our findings may provide novel strategies for the management and treatment of MSL or obesity. PMID- 26148873 TI - Staff nurse perceptions of the impact of mentalization-based therapy skills training when working with borderline personality disorder in acute mental health: a qualitative study. AB - People diagnosed with borderline personality disorder (BPD) are highly prevalent in acute mental health wards, with staff nurses identifying a challenge in working with people who can be significantly distressed. This has contributed to a negative stereotype verging on stigmatization. Mentalization-based therapy (MBT) is a psychological therapy which has been shown to be of benefit to people with a diagnosis of BPD, yet it has been utilized and evaluated only in partial hospitalization and outpatient settings. Despite this, most people diagnosed with BPD will continue to be treated in generic inpatient settings such as acute mental health. Mentalization-based therapy skills training (MBT-S) is a new and cost-effective 2-day workshop aiming to provide generalist practitioners with MBT skills for use in generic settings. This study aimed to capture staff perceptions of the impact of MBT-S on their practice when working with people with a diagnosis of BPD in acute mental health. Through two focus groups, this study assessed the perceptions of nine staff nurses. An interpretive phenomenological approach was utilized in data analysis. Participants found the approach easy to grasp, improving of consistency between staff and flexible in its use in planned or 'off the cuff' discussions. MBT-S promoted empathy and humane responses to self-harm, impacted on participants ability to tolerate risk and went some way to turning the negative perception of BPD through changing the notion of patients as 'deliberately difficult'. Staff felt empowered and more confident in working with people with a diagnosis of BPD. The positive implication for practice was the ease in which the approach was adopted and participants perception of MBT-S as an empowering skill set which also contributed to attitudinal change. In acute mental health environments, which may not have the resources to provide long-term structured treatments to patients, MBT-S could be viewed as ideal as participants applauded its flexibility. The promotion of empathy also sees a move away from iatrogenic damage caused by unhelpful responses to self-harm. In the context of wider research, this study shows that staff nurses find the MBT-S skill set valuable in the generic inpatient setting of acute mental health. PMID- 26148872 TI - Kingella kingae infections in children. AB - BACKGROUND: Improvements in culture techniques and molecular detection methods have led to findings indicating that, particularly in infants and young children, Kingella kingae is a significantly more important pathogen than previously thought. However, despite this, the pediatric community is still largely unaware of the existence of this organism. The aim of this review is therefore to summarise current knowledge of the epidemiology, transmission, clinical presentation, diagnosis and treatment of K. kingae infections in children. DISCUSSION: K. kingae is a common coloniser of the oropharynx, can be transmitted from child to child, and can cause outbreaks of infection. Invasive infections almost exclusively occur in children aged between six months and four years of age, and involve mainly joints and bone, less frequently the endocardium, and very rarely other localisations. With the exception of bacteremia and endocarditis, which can be followed by severe complications, the diseases due to K. kingae are usually accompanied by mild to moderate clinical signs and symptoms, and only slightly altered laboratory data. Moreover, they generally respond to widely used antibiotics, although resistant strains are reported. However, the mild symptoms and limited increase in the levels of acute phase reactants create problems because K. kingae disease may be confused with other clinical conditions that have a similar clinical picture. CONCLUSIONS: Although K. kingae was identified more than 50 years ago, it is poorly known by pediatricians and is not systematically sought in laboratories. Education is therefore necessary in order to reduce the risk of outbreaks, permit the early identification of K. kingae infections, and allow the prompt prescription of adequate therapeutic regimens capable of avoiding the risk of a negative evolution in those cases in which this elusive pathogen can cause significant clinical problems. PMID- 26148874 TI - Overexpression of musashi2 is possibly associated with chemoresistance in T-cell acute lymphoblastic leukemia. PMID- 26148875 TI - Regression of diffuse large B-cell lymphoma in sphenoid and ethmoid sinuses following treatment with loxoprofen. PMID- 26148876 TI - Use of temozolomide instead of cyclophosphamide in diffuse large B-cell lymphoma. PMID- 26148878 TI - Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction. AB - Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980s. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990s, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork producers and biologics companies. PMID- 26148879 TI - What is the responsibility of national government with respect to vaccination? PMID- 26148877 TI - Strengthening the influenza vaccine virus selection and development process: Report of the 3rd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at WHO headquarters, Geneva, Switzerland, 1-3 April 2014. AB - Despite long-recognized challenges and constraints associated with their updating and manufacture, influenza vaccines remain at the heart of public health preparedness and response efforts against both seasonal and potentially pandemic influenza viruses. Globally coordinated virological and epidemiological surveillance is the foundation of the influenza vaccine virus selection and development process. Although national influenza surveillance and reporting capabilities are being strengthened and expanded, sustaining and building upon recent gains has become a major challenge. Strengthening the vaccine virus selection process additionally requires the continuation of initiatives to improve the timeliness and representativeness of influenza viruses shared by countries for detailed analysis by the WHO Global Influenza Surveillance and Response System (GISRS). Efforts are also continuing at the national, regional, and global levels to better understand the dynamics of influenza transmission in both temperate and tropical regions. Improved understanding of the degree of influenza seasonality in tropical countries of the world should allow for the strengthening of national vaccination policies and use of the most appropriate available vaccines. There remain a number of limitations and difficulties associated with the use of HAI assays for the antigenic characterization and selection of influenza vaccine viruses by WHOCCs. Current approaches to improving the situation include the more-optimal use of HAI and other assays; improved understanding of the data produced by neutralization assays; and increased standardization of serological testing methods. A number of new technologies and associated tools have the potential to revolutionize influenza surveillance and response activities. These include the increasingly routine use of whole genome next-generation sequencing and other high-throughput approaches. Such approaches could not only become key elements in outbreak investigations but could drive a new surveillance paradigm. However, despite the advances made, significant challenges will need to be addressed before next-generation technologies become routine, particularly in low-resource settings. Emerging approaches and techniques such as synthetic genomics, systems genetics, systems biology and mathematical modelling are capable of generating potentially huge volumes of highly complex and diverse datasets. Harnessing the currently theoretical benefits of such bioinformatics ("big data") concepts for the influenza vaccine virus selection and development process will depend upon further advances in data generation, integration, analysis and dissemination. Over the last decade, growing awareness of influenza as an important global public health issue has been coupled to ever-increasing demands from the global community for more equitable access to effective and affordable influenza vaccines. The current influenza vaccine landscape continues to be dominated by egg-based inactivated and live attenuated vaccines, with a small number of cell-based and recombinant vaccines. Successfully completing each step in the annual influenza vaccine manufacturing cycle will continue to rely upon timely and regular communication between the WHO GISRS, manufacturers and regulatory authorities. While the pipeline of influenza vaccines appears to be moving towards a variety of niche products in the near term, it is apparent that the ultimate aim remains the development of effective "universal" influenza vaccines that offer longer-lasting immunity against a broad range of influenza A subtypes. PMID- 26148881 TI - The expression of aldehyde dehydrogenase 1 (ALDH1) in ovarian carcinomas and its clinicopathological associations: a retrospective study. AB - BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) is widely used as a specific cancer stem cell marker in a variety of cancers, and may become a promising target for cancer therapy. However, the role of its expression in tumor cells and the microenvironment in different cancers is still controversial. METHODS: To clarify the clinicopathological effect of ALDH1 expression in ovarian carcinoma, a series of 248 cases of paraffin-embedded formalin fixed ovarian carcinoma tissues with long term follow-up information were studied by immunohistochemistry. RESULTS: The immunostaining of ALDH1was variably detected in both tumor cells and the stromal cells, although the staining in tumor cells was not as strong as that in stromal cells. Statistical analyses showed that high ALDH1 expression in tumor cells was significantly associated with histological subtypes, early FIGO stage, well differentiation grade and better survival probability (p < 0.05). The expression of ALDH1 in the stromal cells had no clinicopathological associations in the present study (p > 0.05). CONCLUSIOMS: High expression of cancer stem cell marker ALDH1 in ovarian carcinoma cells may thus portend a favorable prognosis, but its expression in tumor microenvironment may have no role in tumor behavior of ovarian carcinomas. More studies are warranted to find out the mechanisms for this. PMID- 26148880 TI - In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. AB - Targeting immune checkpoint receptors has emerged as an effective strategy to induce immune-mediated cancer regression in the subset of patients who have significant pre-existing anti-tumor immunity. For the remainder, effective anti tumor responses may require vaccination. Radiotherapy, traditionally used to achieve local tumor control, has acquired a new role, that of a partner for immunotherapy. Ionizing radiation has pro-inflammatory effects that facilitate tumor rejection. Radiation alters the tumor to enhance the concentration of effector T cells via induction of chemokines, cytokines and adhesion molecules. In parallel, radiation can induce an immunogenic death of cancer cells, promoting cross-presentation of tumor-derived antigens by dendritic cells to T cells. Newly generated anti-tumor immune responses have been demonstrated post-radiation in both murine models and occasional patients, supporting the hypothesis that the irradiated tumor can become an in situ vaccine. It is in this role, that radiation can be applied to induce anti-tumor T cells in lymphocyte-poor tumors, and possibly benefit patients who would otherwise fail to respond to immune checkpoint inhibitors. This review summarizes preclinical and clinical data demonstrating that radiation acts in concert with antibodies targeting the immune checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4), to induce therapeutically effective anti-tumor T cell responses in tumors otherwise non responsive to anti CTLA-4 therapy. PMID- 26148882 TI - The effect of transcranial direct current stimulation of the motor cortex on exercise-induced pain. AB - PURPOSE: Transcranial direct current stimulation (tDCS) provides a new exciting means to investigate the role of the brain during exercise. However, this technique is not widely used in exercise science, with little known regarding effective electrode montages. This study investigated whether tDCS of the motor cortex (M1) would elicit an analgesic response to exercise-induced pain (EIP). METHODS: Nine participants completed a VO2max test and three time to exhaustion (TTE) tasks on separate days following either 10 min 2 mA tDCS of the M1, a sham or a control. Additionally, seven participants completed 3 cold pressor tests (CPT) following the same experimental conditions (tDCS, SHAM, CON). Using a well established tDCS protocol, tDCS was delivered by placing the anodal electrode above the left M1 with the cathodal electrode above dorsolateral right prefrontal cortex. Gas exchange, blood lactate, EIP and ratings of perceived exertion (RPE) were monitored during the TTE test. Perceived pain was recorded during the CPT. RESULTS: During the TTE, no significant differences in time to exhaustion, RPE or EIP were found between conditions. However, during the CPT, perceived pain was significantly (P < 0.05) reduced in the tDCS condition (7.4 +/- 1.2) compared with both the CON (8.6 +/- 1.0) and SHAM (8.4 +/- 1.3) conditions. CONCLUSION: These findings demonstrate that stimulation of the M1 using tDCS does not induce analgesia during exercise, suggesting that the processing of pain produced via classic measures of experimental pain (i.e., a CPT) is different to that of EIP. These results provide important methodological advancement in developing the use of tDCS in exercise. PMID- 26148883 TI - Induction of human umbilical Wharton's jelly-derived mesenchymal stem cells toward motor neuron-like cells. AB - The most important property of stem cells from different sources is the capacity to differentiate into various cells and tissue types. However, problems including contamination, normal karyotype, and ethical issues cause many limitations in obtaining and using these cells from different sources. The cells in Wharton's jelly region of umbilical cord represent a pool source of primitive cells with properties of mesenchymal stem cells (MSCs). The aim of this study was to determine the potential of human Wharton's jelly-derived mesenchymal stem cells (WJMSCs) for differentiation to motor neuron cells. WJMSCs were induced to differentiate into motor neuron-like cells by using different signaling molecules and neurotrophic factors in vitro. Differentiated neurons were then characterized for expression of motor neuron markers including nestin, PAX6, NF-H, Islet 1, HB9, and choline acetyl transferase (ChAT) by quantitative reverse transcription PCR and immunocytochemistry. Our results showed that differentiated WJMSCs could significantly express motor neuron biomarkers in RNA and protein levels 15 d post induction. These results suggested that WJMSCs can differentiate to motor neuron like cells and might provide a potential source in cell therapy for neurodegenerative disease. PMID- 26148884 TI - Expression of developmental genes in brown fat cells grown in vitro is linked with lipid accumulation. AB - En1, Nr2f1, Gpc4, Sfrp2, Shox2, Tbx15 and Thbd are among the genes involved in development process of an organism in a number of tissues, in particular adipose tissue. Considering the involvement of isobutyl-methyl-xanthine (IBMX), indomethacin, dexamethasone (DEX), triiodothyronine (T3), and insulin in adipocyte differentiation, we propose that these differentiation-inducing agents may regulate differentiation in brown adipose tissue through a developmental process. Stromavascular cells isolated from interscapular brown fat of mice were cultured in DMEM-LG medium. Proliferating brown preadipocytes were differentiated in the presence of IBMX, indomethacin, DEX, T3 and insulin. Pref1 (marker of proliferation stage) and uncoupling protein 1 (UCP1, marker for differentiation stage) were upregulated during proliferation and differentiation, respectively. Relative expression of Pref1, UCP1 and developmental genes was determined in different stages of adipogenesis. En1, Gpc4, Nr2f1, Sfrp2 and Shox2 were upregulated during differentiation. Differentiation of preadipocytes in the absence of IBMX, indomethacin, and DEX resulted in drastic reduction in fat accumulation in differentiated adipocytes with simultaneous decrease in En1, Gpc4, Nr2f1, Sfrp2, Shox2 and Tbx15 gene expression. T3 upregulated the expression of En1, Gpc4, Sfrp2 and Tbx15 genes during differentiation and downregulated Shox2 expression as compared to proliferated state. Insulin upregulated the expression of Shox2. PMID- 26148886 TI - Self test HIV kit goes on sale in UK. PMID- 26148885 TI - Greatest happiness of the greatest number and health inequalities. PMID- 26148887 TI - Diary. New foam filter providers safe drinking water in remote communities. PMID- 26148888 TI - Response to griffiths paper - public health specialist workforce training. PMID- 26148889 TI - Policy. PMID- 26148890 TI - Creating Healthy Places: a whole system approach to food and active living. PMID- 26148891 TI - CoppaFeel!: on a mission to educate young people about breast cancer. PMID- 26148892 TI - Food fraud and allergen management. PMID- 26148893 TI - How storytelling can bias sensory perceptions among young students. PMID- 26148894 TI - Oral health among UK prisoners. PMID- 26148895 TI - Shift in disease burden from communicable to non-communicable diseases: aiming to achieve Universal Health Coverage in Nepal. PMID- 26148896 TI - Plants and green spaces provide more than just aesthetic benefits. PMID- 26148898 TI - Emerging role of CEBP-alpha mutations in acute myeloid leukemia. PMID- 26148899 TI - Green to red photoconversion of GFP for protein tracking in vivo. AB - A variety of fluorescent proteins have been identified that undergo shifts in spectral emission properties over time or once they are irradiated by ultraviolet or blue light. Such proteins are finding application in following the dynamics of particular proteins or labelled organelles within the cell. However, before genes encoding these fluorescent proteins were available, many proteins have already been labelled with GFP in transgenic cells; a number of model organisms feature collections of GFP-tagged lines and organisms. Here we describe a fast, localized and non-invasive method for GFP photoconversion from green to red. We demonstrate its use in transgenic plant, Drosophila and mammalian cells in vivo. While genes encoding fluorescent proteins specifically designed for photoconversion will usually be advantageous when creating new transgenic lines, our method for photoconversion of GFP allows the use of existing GFP-tagged transgenic lines for studies of dynamic processes in living cells. PMID- 26148900 TI - Adhesion of dry and wet electrostatic capture silk of uloborid spider. AB - We demonstrate the impressive adhesive qualities of uloborid spider orb-web capture when dry, which are lost when the nano-filament threads are wetted. A force sensor with a 50 nN-1 mN detection sensitively allowed us to measure quantitatively the stress-strain characteristics of native silk threads in both the original dry state and after wetting by controlled application of water mist with droplet sizes ranging between 3 and 5 MUm and densities ranging between 10(4) and 10(5) per mm(3). Stress forces of between 1 and 5 MUN/MUm(2) in the native, dry multifilament thread puffs were reduced to between 0.1 and 0.5 MUN/MUm(2) in the wetted collapsed state, with strain displacements reducing from between 2 and 5 mm in the dry to 0.10-0.12 mm in the wetted states. We conclude that wetting cribellate threads reduce their van der Waals adhesion with implications on the thread's adhesive strength under tension. This should be considered when discussing the evolutionary transitions of capture silks from the ancestral dry-state nano-filaments of the cribellate spider taxa to the wet-state glue-droplets of the ecribellate taxa. PMID- 26148901 TI - Retrospective analysis of second-line chemotherapy outcomes with paclitaxel or docetaxel in correlation with STMN1 polymorphism in advanced non-small cell lung cancer patients. AB - PURPOSE: Second-line chemotherapy of advanced non-small cell lung cancer (NSCLC) with docetaxel or pemetrexed allows to achieve objective response rate only in 5 10 % of patients. Recent studies have shown that single nucleotide polymorphisms (SNPs) in genes encoding proteins which regulate dynamics of microtubules may be considered as predictive factors of response to taxane-based chemotherapy. STMN1 gene encodes stathmin 1, which plays role in cell division by regulation of microtubules depolarisation, and this process may be associated with taxanes' effectiveness. MATERIALS AND METHODS: Using HRM-PCR technique, we evaluated the 2166C>T SNP of STMN1 gene in DNA from peripheral blood leucocytes of 54 advanced NSCLC patients treated in second-line monotherapy with docetaxel or paclitaxel. RESULTS: Patients with TT genotype of STMN1 gene demonstrated significantly longer progression-free survival (PFS) and the lower risk of early disease progression after second-line treatment compared to patients with other STMN1 genotypes (median PFS: 7 and 2 months; p = 0.0154; HR = 0.371; 95 % CI 0.184 0.743). Early disease progression during second-line chemotherapy was significantly more frequently observed in patients with CC genotype of STMN1 in contrast to patients with presence of T allele (median PFS: 2 and 4 months; p = 0.0385; HR = 1.776; 95 % CI 0.905-3.445). CONCLUSION: Only selected NSCLC patients could benefit from second-line chemotherapy. Therefore, investigations of novel predictive molecular factors for proper qualification of patients to second-line taxane-based chemotherapy are justified. Studied SNP of STMN1 gene may have potential predictive role in such therapy. PMID- 26148902 TI - Synthesis of nitrogen-doped carbon nanostructures from polyurethane sponge for bioimaging and catalysis. AB - A facile and environmentally friendly method was developed for the fabrication of N-doped carbon nanomaterials by hydrothermal treatment using polyurethane (PU) sponge as a carbon source. We have demonstrated that the hydrothermal decomposition of PU sponge involves top-down hydrolysis and bottom-up polymerization processes for the synthesis of N-doped carbon dots (N-CDs). Fluorescence spectroscopy and cytotoxicity studies indicated that these highly soluble N-CDs show excellent photoluminescence properties and low cytotoxicity, and can be used as good probes for cellular imaging. Additionally, the N-doped hollow carbon nanostructures can be designed using a simple template method. The prepared N-doped double-shelled hollow carbon nanotubes exhibited excellent ORR electrocatalytic activity and superior durability. Indeed, our method described here can provide an efficient way to synthesize N-doped carbon-based materials for a broad range of applications. PMID- 26148903 TI - Anti-C1q autoantibodies from systemic lupus erythematosus patients activate the complement system via both the classical and lectin pathways. AB - Autoantibodies against complement C1q (anti-C1q) strongly correlate with the occurrence of lupus nephritis and hypocomplementemia in systemic lupus erythematosus (SLE). Although a direct pathogenic role of anti-C1q has been suggested, the assumed complement-activating capacity remains to be elucidated. Using an ELISA-based assay, we found that anti-C1q activate the classical (CP) and lectin pathways (LP) depending on the anti-C1q immunoglobulin-class repertoire present in the patient's serum. IgG anti-C1q resulted in the activation of the CP as reflected by C4b deposition in the presence of purified C1 and C4 in a dose-dependent manner. The extent of C4b deposition correlated with anti-C1q levels in SLE patients but not in healthy controls. Our data indicate that SLE patient-derived anti-C1q can activate the CP and the LP but not the alternative pathway of complement. These findings are of importance for the understanding of the role of anti-C1q in SLE suggesting a direct link to hypocomplementemia. PMID- 26148904 TI - Global optimization and oxygen dissociation on polyicosahedral Ag32Cu6 core-shell cluster for alkaline fuel cells. AB - The structure of 38 atoms Ag-Cu cluster is studied by using a combination of a genetic algorithm global optimization technique and density functional theory (DFT) calculations. It is demonstrated that the truncated octahedral (TO) Ag32Cu6 core-shell cluster is less stable than the polyicosahedral (pIh) Ag32Cu6 core shell cluster from the atomistic models and the DFT calculation shows an agreeable result, so the newfound pIh Ag32Cu6 core-shell cluster is further investigated for potential application for O2 dissociation in oxygen reduction reaction (ORR). The activation energy barrier for the O2 dissociation on pIh Ag32Cu6 core-shell cluster is 0.715 eV, where the d-band center is -3.395 eV and the density of states at the Fermi energy level is maximal for the favorable absorption site, indicating that the catalytic activity is attributed to a maximal charge transfer between an oxygen molecule and the pIh Ag32Cu6 core-shell cluster. This work revises the earlier idea that Ag32Cu6 core-shell nanoparticles are not suitable as ORR catalysts and confirms that Ag-Cu nanoalloy is a potential candidate to substitute noble Pt-based catalyst in alkaline fuel cells. PMID- 26148905 TI - The use of Brainsuite iCT for frame-based stereotactic procedures. AB - BACKGROUND: Frame-based stereotactic procedures are the gold standard because of their superior stereotactic accuracy. The procedure used to be in multiple steps and was especially cumbersome and hazardous in intubated patients. A single-step procedure using intraoperative CT was created to optimize the procedures. METHODS: A combined fixation and low profile frame holder was designed for the operating table, allowing positioning for the scanning procedure immediately followed by the surgical biopsy procedure with the same positioning and head fixation. For placement of depth electrodes immediate CT control of positioning was feasible. RESULTS: In the first 8 months the procedure was successfully used 65 times including 8 times in pediatric cases. The procedure duration in awake patients was on average 81 min (range 33 to 202) and in intubated patients (children) on average 89 min (median 89, 78-100). DISCUSSION: This study demonstrates that frame-based stereotactic procedures in all brain locations are a feasible and practical technique with improved workflow and added patient safety and comfort. PMID- 26148906 TI - Development of a new high-resolution intraoperative imaging system (dual-image videoangiography, DIVA) to simultaneously visualize light and near-infrared fluorescence images of indocyanine green angiography. AB - BACKGROUND: Intraoperative indocyanine green videoangiography (ICG-VA) has been widely used in vascular surgery, where vessels are clearly shown as white on a black background. However, other structures cannot be observed during ICG-VA. We have developed a new, high-resolution intraoperative imaging system (dual-image VA [DIVA]) to simultaneously visualize both light and near-infrared (NIR) fluorescence images from ICG-VA, allowing observation of other structures. METHODS: The operative field was illuminated via an operating microscope by halogen and xenon lamps with a filter to eliminate wavelengths over 780 nm. In the camera unit, visible light was filtered to 400-700 nm and NIR fluorescence emission light was filtered to 800-900 nm using a special sensor unit with an optical filter. Light and NIR fluorescence images were simultaneously visualized on a single monitor. RESULTS: Our system clearly visualized the operative field together with fluorescence-enhanced blood flow. In aneurysm surgeries, we could confirm incomplete clipping with the neck remnant or with remnant flow into the aneurysm. In cases of arteriovenous malformation or arteriovenous fistula, feeding arteries and draining veins were easily distinguished. CONCLUSIONS: This system allows observation of the operative field and enhanced blood flow by ICG together in real time and may facilitate various types of neurovascular surgery. PMID- 26148907 TI - Cerebral venous thrombosis associated with tuberculous meningitis: a rare complication of a common disease. PMID- 26148908 TI - A Prospective Ultrasound Study of Prenatal Growth in Infant Siblings of Children With Autism. AB - Numerous studies have observed that a proportion of infants later diagnosed with autism spectrum disorder (ASD) experience accelerated head growth during the first years of life. An emerging methodology for examining the developmental trajectory prior to a diagnosis of ASD is to investigate siblings of affected individuals. The current study is the first prospective investigation of fetal growth in siblings of children with ASD. Two groups of pregnant women were recruited as part of the PRegnancy Investigation of Siblings and Mothers of children with autism cohort in Perth, Western Australia. The "high risk" group (n = 23) comprised pregnant women who have an existing child with a diagnosis of ASD and the "low risk" group (n = 36) comprised pregnant mothers who have an existing child who has developed typically. Prenatal ultrasounds were procured at multiple time-points throughout the second- and third-trimesters, enabling an examination of growth trajectories. Growth measurements were then compared for the high- and low-risk fetuses. Mixed linear regression models identified no significant differences between the high- and low-risk fetuses in the rate of prenatal head and body growth throughout the second- and third-trimester (all P-values >0.05). Similarly, there were no significant differences observed when comparing high and low risk groups on a ratio of head circumference relative to body size (beta = 0.019, P = 0.75). Future studies may consider looking beyond the macro architecture of the prenatal brain and examine the growth of brain subregions that have been implicated in the presentation of ASD symptoms. PMID- 26148909 TI - General practitioners' 'lived experience' of assessing psychological distress in cancer patients: an exploratory qualitative study. AB - While psychological distress in cancer patients is common, little is known about how general practitioners (GPs) assess distress. Using semi-structured interviews, a phenomenological study of seven GPs was conducted to explore GPs' experiences of assessing distress. Findings revealed five themes: (1) Being in the Relay Team - receiving and passing the baton: where the assessment of distress was conceptualised as a relay baton passed between a team of health care professionals, with GPs most involved at diagnosis and in the palliative phase. (2) Being in a Relationship: where the doctor-patient relationship was described as a powerful facilitator to assessment. (3) Being Skilled: where GPs perceive they are skilled at assessment adopting a patient-centred approach. (4) Being Challenged - encountering barriers: challenges with assessment were identified regarding the GPs' own emotions, patient related factors and time; the duality of family as both barrier and facilitator was voiced. (5) The Intruder in the Room: where GPs did not use validated screening tools which were viewed as an intruder in the doctor-patient relationship. Further research to objectively assess GPs' skills in distress assessment and attitudes towards the use of screening tools within the cancer care context are merited. PMID- 26148910 TI - The role of latex agglutination test for the etiological diagnosis of pleural effusion in children and adolescents. AB - INTRODUCTION: The etiological diagnosis of pleural effusion is a difficult task because the diagnostic tools can only establish a definitive etiological diagnosis in at most 76% of cases. OBJECTIVES: To verify the diagnostic accuracy of the latex agglutination test (LAT) for the etiological diagnosis of pleural effusions caused by Streptococcus pneumoniae and Haemophilus influenzae type b. METHODS: After thoracocentesis, paired fresh samples of pleural fluid from 418 children and adolescents were included in this investigation. They were tested blindly and simultaneously through counterimmunoelectrophoresis (CIE) and LAT for both bacteria. Sensitivity, specificity, predictive values and likelihood ratios (LR) were calculated taking CIE as a reference standard. RESULTS: The sensitivity and specificity of LAT was 100% (95% confidence interval, 94.4%-100%) and 83.3% (95% confidence interval, 79.0%-87.0%), respectively, whereas the positive (calculated from Bayes' theorem) and negative predictive values were, respectively, lower than 1% and 100% (95% confidence interval, 98.8%-100%). Positive and negative LR were 6.0 (95% confidence interval, 4.7-7.6) and zero, respectively. CONCLUSIONS: Our results suggest that LAT is a useful tool for the etiological diagnosis of pleural effusion. It is a reliable, rapid, simple to perform and shows an excellent yield in our studied population, helping to prescribe appropriate antibiotics for this clinical condition. PMID- 26148911 TI - The Mediterranean diet: culture, health and science. PMID- 26148912 TI - Fruit and vegetables and cancer risk: a review of southern European studies. AB - High intakes of fruit and vegetables may reduce the risk of cancer at several sites. Evidence has been derived mainly from case-control studies. We reviewed the relationship between consumption of vegetables and fruit and the risk of several common cancers in a network of Italian and Swiss case-control studies including over 10,000 cases of fourteen different cancers and about 17,000 controls. Data were suggestive of a protective role of vegetable intake on the risk of several common epithelial cancers. OR for the highest compared with the lowest levels of consumption ranged from 0.2 (larynx, oral cavity and pharynx) to 0.9 (prostate). Inverse associations were found for both raw and cooked vegetables, although for upper digestive tract cancers the former were somewhat stronger. Similar inverse associations were found for cruciferous vegetables. Frequent consumption of allium vegetables was also associated with reduced risk of several cancers. Fruit was a favourable correlate of the risk of several cancers, particularly of the upper digestive tract, with associations generally weaker than those reported for vegetables. A reduced risk of cancers of the digestive tract and larynx was found for high consumption of citrus fruit. Suggestive protections against several forms of cancer, mainly digestive tract cancers, were found for high consumption of apples and tomatoes. High intakes of fibres, flavonoids and proanthocyanidins were inversely related to various forms of cancer. In conclusion, data from our series of case-control studies suggested a favourable role of high intakes of fruit and vegetables in the risk of many common cancers, particularly of the digestive tract. This adds evidence to the indication that aspects of the Mediterranean diet may have a favourable impact not only on CVD, but also on several common (epithelial) cancers, particularly of the digestive tract. PMID- 26148913 TI - Diets and morbid tissues--history counts, present counts. AB - Body fat distribution, especially visceral fat accumulation, may contribute more than total fat mass per se to the development of metabolic and cardiovascular disorders. Early prevention highly improves health outcomes later in life, especially when considering such cumulative conditions as atherosclerosis. However, as these processes emerge to be partly reversible, dietary and lifestyle interventions at any age and health condition are greatly beneficial. Given the worldwide abundance of metabolic and cardiovascular disorders, the identification and implementation of strategies for preventing or reducing the accumulation of morbid fat tissues is of great importance for preventing and regressing atherosclerosis. This review focuses on dietary strategies and specific food components that were demonstrated to alter body fat distribution and regression of atherosclerosis. Different properties of various adipose depots (superficial subcutaneous, deep subcutaneous and visceral fat depots) and their contribution to metabolic and cardiovascular disorders are briefly discussed. Visceral obesity and atherosclerosis should be approached as modifiable rather than ineluctable conditions. PMID- 26148914 TI - Nuts and CVD. AB - Nuts are nutrient-dense foods with complex matrices rich in unsaturated fatty acids and other bioactive compounds, such as l-arginine, fibre, healthful minerals, vitamin E, phytosterols and polyphenols. By virtue of their unique composition, nuts are likely to beneficially affect cardiovascular health. Epidemiological studies have associated nut consumption with a reduced incidence of CHD in both sexes and of diabetes in women, but not in men. Feeding trials have clearly demonstrated that consumption of all kinds of nuts has a cholesterol lowering effect, even in the context of healthy diets. There is increasing evidence that nut consumption has a beneficial effect on oxidative stress, inflammation and vascular reactivity. Blood pressure, visceral adiposity and the metabolic syndrome also appear to be positively influenced by nut consumption. Contrary to expectations, epidemiological studies and clinical trials suggest that regular nut consumption is not associated with undue weight gain. Recently, the PREvencion con DIeta MEDiterranea randomised clinical trial of long-term nutrition intervention in subjects at high cardiovascular risk provided first class evidence that regular nut consumption is associated with a 50 % reduction in incident diabetes and, more importantly, a 30 % reduction in CVD. Of note, incident stroke was reduced by nearly 50 % in participants allocated to a Mediterranean diet enriched with a daily serving of mixed nuts (15 g walnuts, 7.5 g almonds and 7.5 g hazelnuts). Thus, it is clear that frequent nut consumption has a beneficial effect on CVD risk that is likely to be mediated by salutary effects on intermediate risk factors. PMID- 26148915 TI - Moderate red wine consumption is associated with a lower prevalence of the metabolic syndrome in the PREDIMED population. AB - Previous studies on the association between alcohol intake and the development of the metabolic syndrome (MetS) have yielded inconsistent results. Besides, few studies have analysed the effects of red wine (RW) consumption on the prevalence of the MetS and its components. As moderate RW drinkers have a better lipid profile and lower incidence rates of diabetes, hypertension and abdominal obesity, all components of the MetS, it was hypothesised that moderate RW consumption could be associated with a lower prevalence of the MetS. In the present cross-sectional study of 5801 elderly participants at a high cardiovascular risk included in the PREDIMED (Prevencion con Dieta Mediterranea) study, 3897 fulfilled the criteria of the MetS at baseline. RW intake was recorded using a validated 137-item FFQ. Multiple logistic regression analysis was carried out to estimate the association between RW intake and the prevalence of the MetS. Compared with non-drinkers, moderate RW drinkers (>= 1 drink/d) were found to have a reduced risk of prevalent MetS (OR 0.56, 95 % CI 0.45, 0.68; P < 0.001), a lower risk of having an abnormal waist circumference (OR 0.59, 95 % CI 0.46, 0.77; P < 0.001), low HDL-cholesterol concentrations (OR 0.42, 95 % CI 0.32, 0.53; P < 0.001), high blood pressure (OR 0.28, 95 % CI 0.17, 0.45; P < 0.001) and high fasting plasma glucose concentrations (OR 0.67, 95 % CI 0.54, 0.82; P < 0.001) after adjusting for several confounders. This association was found to be stronger in female participants, in participants aged < 70 years and in participants who were former or current smokers. No significant association was found between RW intake (>= 1 drink/d) and TAG concentrations. In conclusion, moderate RW consumption is associated with a lower prevalence of the MetS in an elderly Mediterranean population at a high cardiovascular risk. PMID- 26148916 TI - Fermented dairy food and CVD risk. AB - Fermented dairy foods such as yoghurt and cheese are commonly found in the Mediterranean diet. Recent landmark research has confirmed the effect of the Mediterranean diet on reducing the CVD risk, but the relative contributions of fermented dairy foods have not been fully articulated. The present study provides a review of the relationship between fermented dairy foods consumption and CVD risk in the context of the whole diet. Studies show that people who eat healthier diets may be more likely to consume yoghurt, so there is a challenge in attributing separate effects to yoghurt. Analyses from large population studies list yoghurt as the food most negatively associated with the risk of weight gain (a problem that may lead to CVD). There is some suggestion that fermented dairy foods consumption (yoghurt or cheese) may be associated with reduced inflammatory biomarkers associated with the development of CVD. Dietary trials suggest that cheese may not have the same effect on raising LDL-cholesterol levels as butter with the same saturated fat content. The same might be stated for yoghurt. The use of different probiotic cultures and other aspects of study design remain a problem for research. Nevertheless, population studies from a range of countries have shown that a reduced risk of CVD occurs with the consumption of fermented dairy foods. A combination of evidence is necessary, and more research is always valuable, but indications remain that fermented dairy foods such as cheese and yoghurt are integral to diets that are protective against CVD. PMID- 26148917 TI - A perspective on vegetarian dietary patterns and risk of metabolic syndrome. AB - The vegetarian dietary pattern is traditionally a plant-based diet that includes fruits, vegetables, cereals, legumes, nuts, vegetable oils, soya, and possibly dairy products and/or eggs. Vegetarians and other populations who follow a plant based dietary pattern enjoy longevity. Specifically, vegetarian dietary patterns have been associated with a lower risk for developing IHD, type 2 diabetes, hypertension, specific cancers, lower all-cause mortality and reduction in cause specific mortality. The prevalence of the metabolic syndrome (MetS) in the USA is approximately 20 % and is currently increasing in developing countries in line with the obesity epidemic. The health care costs associated with the MetS are on a magnitude of 1.6 overall compared with healthy individuals, which makes it an important public health problem. Current evidence from several cross-sectional and case-control studies shows an association between consumption of a vegetarian dietary pattern and a reduced prevalence or risk of developing the MetS. There is a need for further research to be conducted, particularly prospective cohort studies to evaluate the effect of vegetarian dietary patterns on reducing the incidence of the MetS and, clinical trials should be designed to explore vegetarian dietary patterns for the reversal of the MetS in high-risk populations. This research could contribute to reduce the societal and economic burdens associated with the disorder. PMID- 26148918 TI - Virgin olive oil: a key food for cardiovascular risk protection. AB - Olive oil is considered to be one of the most healthy dietary fats. However, several types of olive oils are present in the market. A key question for the consumer is: What of the olive oils is the best when concerning nutritional purposes? With the data available at present, the answer is: the Virgin Olive Oil (VOO), rich in phenolic compounds. On November 2011, the European Food Safety Authority released a claim concerning the benefits of daily ingestion of olive oil rich in phenolic compounds, such as VOO. In this review, we summarised the key work that has provided the evidence of the benefits of VOO consumption on other types of edible oils, even olive oils. We focused on data from randomised, controlled human studies, which are capable of providing the evidence of Level I that is required for performing nutritional recommendations at population level. PMID- 26148919 TI - Relationship between bread and obesity. AB - Some studies have indicated that promoting the Mediterranean diet pattern as a model of healthy eating may help to prevent weight gain and the development of overweight/obesity. Bread consumption, which has been part of the traditional Mediterranean diet, has continued to decline in Spain and in the rest of the world, because the opinion of the general public is that bread fattens. The present study was conducted to assess whether or not eating patterns that include bread are associated with obesity and excess abdominal adiposity, both in the population at large or in subjects undergoing obesity management. The results of the present review indicate that reducing white bread, but not whole-grain bread, consumption within a Mediterranean-style food pattern setting is associated with lower gains in weight and abdominal fat. It appears that the different composition between whole-grain bread and white bread varies in its effect on body weight and abdominal fat. However, the term 'whole-grain bread' needs to be defined for use in epidemiological studies. Finally, additional studies employing traditional ways of bread production should analyse this effect on body-weight and metabolic regulation. PMID- 26148920 TI - Does cooking with vegetable oils increase the risk of chronic diseases?: a systematic review. AB - Overweight/obesity, CVD and type 2 diabetes are strongly associated with nutritional habits. High consumption of fried foods might increase the risk of these disorders. However, it is not clear whether the use of vegetables oils for cooking increases the risk of chronic diseases. We systematically searched for published studies that assessed the association between vegetable oil consumption including fried food consumption and the risk of overweight/obesity or weight gain, T2DM or the metabolic syndrome, and CVD or hypertension in the following databases: PubMed; Web of Science; Google Scholar. Keywords such as 'fried food' or 'vegetable oil' or 'frying' or 'frying oils' or 'dietary fats' and 'weight gain' or 'overweight' or 'obesity' or 'CHD' or 'CVD' or 'type 2 diabetes' or 'metabolic syndrome' were used in the primary search. Additional published reports were obtained through other sources. A total of twenty-three publications were included based on specific selection criteria. Based on the results of the studies included in the present systematic review, we conclude that (1) the myth that frying foods is generally associated with a higher risk of CVD is not supported by the available evidence; (2) virgin olive oil significantly reduces the risk of CVD clinical events, based on the results of a large randomised trial that included as part of the intervention the recommendation to use high amounts of virgin olive oil, also for frying foods; and (3) high consumption of fried foods is probably related to a higher risk of weight gain, though the type of oil may perhaps modify this association. PMID- 26148921 TI - The Mediterranean diet: health, science and society. AB - The Mediterranean diet (MD) emerged as a healthy food regimen long before it could be recognised which nutrients or foods were responsible for its observed benefits, and it was only in the middle of the last century that the first scientific approach 'The Seven Countries Study' appeared. Epidemiological and anthropological studies of the MD converged, first by investigating at single nutrients or foods, then by adopting the more holistic approach of dietary patterns (DP), and now with a molecular approach. These studies resulted in convincing evidence that a MD decreases the risk of all-cause mortality and cardiovascular mortality and incidence. A risk reduction of developing type 2 diabetes is probable. Evidence is less stringent for other metabolic diseases and all cancers but from possible to probable for some cancer sites. Although DP showed that the MD has to be considered in its totality, olive oil could have a specific role. Lifestyle factors such as physical activity for energy balance, outdoor life for vitamin D synthesis and conviviality are also probably partly responsible for the health benefits. The MD is a lifestyle well suited for coping not only with personal health but also with wider societal concerns in relation to environment, public health and economy. PMID- 26148922 TI - Possible adverse effects of frying with vegetable oils. AB - The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases. PMID- 26148923 TI - Fish, a Mediterranean source of n-3 PUFA: benefits do not justify limiting consumption. AB - Fish is an important source of energy, high-quality proteins, fat, vitamins and minerals. Within lipids, n-3 long-chain PUFA (n-3 LC PUFA), mainly EPA and DHA, play an important role in health promotion and disease prevention. In contrast to the potential health benefits of dietary fish intake, certain chemical pollutants, namely heavy metals and some organic compounds, contained in seafood have emerged as an issue of concern, particularly for frequent fish consumers and sensitive groups of populations. The present review summarises the health benefits and risks of fish consumption. n-3 LC-PUFA are key compounds of cell membranes and play an important role in human health from conception through every stage of human development, maturation and ageing. DHA has a major role in the development of brain and retina during fetal development and the first 2 years of life and positively influences neurodevelopment, mainly visual acuity and cognitive functions. n-3 LC-PUFA are also effective in preventing cardiovascular events (mainly stroke and acute myocardial infarction) especially in persons with high cardiovascular risk. By contrast, there is convincing evidence of adverse neurological/neurodevelopmental outcomes in infants and young children associated with methylmercury exposure during fetal development due to maternal fish consumption during pregnancy. Dioxins and polychlorinated biphenyls present in contaminated fish may also develop a risk for both infants and adults. However, for major health outcomes among adults, the vast majority of epidemiological studies have proven that the benefits of fish intake exceed the potential risks with the exception of a few selected species in sensitive populations. PMID- 26148924 TI - Review of nut phytochemicals, fat-soluble bioactives, antioxidant components and health effects. AB - The levels of phytochemicals (total phenols, proanthocyanidins, gallic acid + gallotannins, ellagic acid + ellagitannins, flavonoids, phenolic acids, stilbenes and phytates), fat-soluble bioactives (lipid, tocols, phytosterols, sphingolipids, carotenoids, chlorophylls and alkyl phenols) as well as natural antioxidants (nutrient and non-nutrient) present in commonly consumed twelve nuts (almond, Brazil nut, cashew, chestnut, hazelnut, heartnut, macadamia, peanut, pecan, pine nut, pistachio and walnut) are compared and reported. Recent studies adding new evidence for the health benefits of nuts are also discussed. Research findings from over 112 references, many of which have been published within last 10 years, have been compiled and reported. PMID- 26148925 TI - Nutrition attributes and health effects of pistachio nuts. AB - Epidemiological and/or clinical trials have suggested that nut consumption has a beneficial impact on health outcomes such as hypertension, diabetes, CVD, cancer, other inflammatory conditions and total mortality. Nuts are nutrient-dense foods with a healthy fatty acid profile, as well as provide other bioactive compounds with recognised health benefits. Among nuts, pistachios have a lower fat and energy content and the highest levels of K, gamma-tocopherol, vitamin K, phytosterols, xanthophyll carotenoids, certain minerals (Cu, Fe and Mg), vitamin B6 and thiamin. Pistachios have a high antioxidant and anti-inflammatory potential. The aforementioned characteristics and nutrient mix probably contribute to the growing body of evidence that consumption of pistachios improves health. The present review examines the potential health effects of nutrients and phytochemicals in pistachios, as well as epidemiological and clinical evidence supporting these health benefits. PMID- 26148926 TI - The role of olive oil in disease prevention: a focus on the recent epidemiological evidence from cohort studies and dietary intervention trials. AB - Consumption of olive oil within the Mediterranean diet has been long known to have many health benefits. However, only over the last decade has epidemiological research confirmed its protective role against developing several chronic diseases. The objective of this review was to give an overview of the state of art epidemiological evidence concerning the relationship between olive oil and key public health outcomes including mortality, CVD, diabetes, metabolic syndrome (MetS), obesity and cancer, with a particular focus on recent results from cohort studies and dietary intervention trials. Recent epidemiological research has shown that regular consumption of olive oil is associated with increased longevity. This benefit is partly due to the olive oil's unequivocal cardio protective role. There is converging evidence on the benefits of olive oil for preventing several CVD risk factors, including diabetes, MetS and obesity. Olive oil is also implicated in preventing certain cancers, with the most promising findings for breast and digestive tract cancers, although the data are still not entirely consistent and mainly from case-control studies. These health benefits are supported by strong mechanistic evidence from experimental studies, demonstrating that specific components of olive oil have antihypertensive, antithrombotic, antioxidant, antiinflammatory and anticarcinogenic action. Despite the accumulating epidemiological research, there is still a lack of consistent results from high-quality studies for many health outcomes (i.e. certain cancers and metabolism-related disorders). Further research is mandatory, above all from prospective studies and randomised dietary intervention trials when feasible, to confirm some of the still potential health benefits. PMID- 26148927 TI - Obesity not associated with severity among hospitalized adults with seasonal influenza virus infection. AB - We examined seasonal influenza severity [artificial ventilation, intensive care unit (ICU) admission, and radiographic-confirmed pneumonia] by weight category among adults hospitalized with laboratory-confirmed influenza. Using multivariate logistic regression models, we found no association between obesity or severe obesity and artificial ventilation or ICU admission; however, overweight and obese patients had decreased risk of pneumonia. Underweight was associated with pneumonia (adjusted odds ratio 1.31; 95 % confidence interval 1.04, 1.64). PMID- 26148928 TI - Mycobacterium abscessus ventriculoperitoneal shunt infection and review of the literature. AB - A 30-year-old man with history of neonatal hydrocephalus requiring ventriculoperitoneal shunt placement presented with Mycobacterium abscessus shunt infection despite no shunt manipulation over 10 years prior to presentation. Cure was not achieved until complete removal of all CNS shunt foreign body was performed despite initial adequate antimicrobial therapy. PMID- 26148929 TI - Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection. AB - BACKGROUND: Overproduction of pro-inflammatory cytokines and chemokines is frequently associated with severe clinical manifestations in patients infected with influenza A/H1N1 virus. Micro-RNAs (miRNAs) are highly conserved small non coding RNA molecules that post-transcriptionally regulate gene expression and are potential biomarkers and therapeutic targets in different inflammatory conditions. METHODS: We studied the circulating and miRNA profiles in critically ill A/H1N1 patients, A/H1N1 patients with milder disease, asymptomatic housemates and healthy controls. Cytokine, chemokine and growth factors that were potential targets of differentially expressed miRNAs were assessed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and interactome analysis of these miRNAs were also performed. RESULTS: Critically ill patients exhibited a significant over-expression of circulating miR-150 (p<0.005) when compared to patients with milder disease. miR-29c, miR-145 and miR-22 were differentially expressed in patients with severe A/H1N1 disease whereas miR-210, miR-126 and miR 222 were downregulated in individuals exposed to the A/H1N1 virus. Significant correlations (p<0.05) between circulating levels of miR-150 with IL-1ra, IL-2, IL 6, CXCL8, IFN-gamma, CXCL10 and G-CSF were detected, particularly in critically ill patients. CONCLUSION: The up-regulation of miR-150 is associated with poorer outcomes of A/H1N1 infection. The differential expression of miRNAs related with immune processes in severe A/H1N1 disease supports the potential role of these miRNAs as biomarkers of disease progression. PMID- 26148930 TI - A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in Patients With Ischemic or Nonischemic Heart Failure. AB - RATIONALE: Allogeneic mesenchymal precursor cells (MPCs) have been effective in large animal models of ischemic and nonischemic heart failure (HF). OBJECTIVE: To evaluate the feasibility and safety of 3 doses (25, 75, or 150 million cells) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial. METHODS AND RESULTS: We sequentially allocated 60 patients to a dosing cohort (20 per dose group) and randomized them to transendocardial MPC injections (n=15) or mock procedures (n=5). The primary objective was safety, including antibody testing. Secondary efficacy end points included major adverse cardiac events (MACE; cardiac death, myocardial infarction, or revascularization), left ventricular imaging, and other clinical-event surrogates. Safety and MACE were evaluated for up to 3 years. MPC injections were feasible and safe. Adverse events were similar across groups. No clinically symptomatic immune responses were noted. MACE was seen in 15 patients: 10 of 45 (22%) MPC-treated and 5 of 15 (33%) control patients. We found no differences between MPC-treated and control patients in survival probability, MACE-free probability, and all-cause mortality. We conducted a post hoc analysis of HF-related MACE (HF hospitalization, successfully resuscitated cardiac death, or cardiac death) and events were significantly reduced in the 150 million MPC group (0/15) versus control (5/15; 33%), 25 million MPC group (3/15; 20%), and 75 million MPC group (6/15; 40%); the 150 million MPC group differed significantly from all groups according to Kaplan Meier statistics >3 years (P=0.025 for 150 million MPC group versus control). CONCLUSIONS: Transendocardial injections of allogeneic MPCs were feasible and safe in chronic HF patients. High-dose allogeneic MPCs may provide benefits in this population. PMID- 26148931 TI - Clinical features, diagnostic findings, and treatment of Susac syndrome: a case series. AB - BACKGROUND: Susac syndrome (SS) is a rare, presumed autoimmune condition characterized by the clinical triad of branch retinal artery occlusions (BRAOs), encephalopathy, and sensorineural hearing loss. The aim of this study was to evaluate clinical features, diagnostic results, treatment, and outcomes in SS. METHODS: Five patients with SS were referred to three tertiary care centers in Boston. The observation period across these patients was 7-57months. RESULTS: At initial presentation, none of the patients demonstrated the complete triad of BRAO, sensorineural hearing loss, and encephalopathy. The interval between symptom onset and diagnosis of SS was 4-30weeks. Brain MRI findings thought to be characteristic of SS (including callosal fluid-attenuated inversion recovery (FLAIR) hyperintense and T1 hypointense lesions) were frequently absent. Microinfarcts noted on diffusion-weighted imaging (DWI), BRAOs and vessel wall hyperfluorescence on fluorescein angiography (FA) were present in all cases in the acute encephalopathic phase. All patients treated with glucocorticoids and intravenous immunoglobulins (IVIg) alone experienced further clinical progression until additional immunosuppressive therapy was instituted. CONCLUSIONS: The rarity of SS, its incomplete and variable presentation, and the nonspecific imaging findings invariably led to delayed diagnosis. DWI and FA should be used to identify the acute microvascular injury and monitor treatment response. Immunomodulatory agents more potent than glucocorticoids and IVIg might be required to control the disease. PMID- 26148933 TI - Olfactory and gustatory dysfunction in Myasthenia gravis: A study in Turkish patients. AB - OBJECTIVE: Myasthenia gravis (MG) is commonly viewed as a muscle disorder. Less is known about neurosensory function and dysfunction in MG. We aim to evaluate olfactory and gustatory behavior in Turkish patients with MG, and compare these results with age and sex-matched healthy controls. MATERIAL/METHODS: 30 individuals with MG, and 30 healthy volunteers were studied. Olfactory function was studied with the Sniffin' sticks test. Taste strip test was used for studying taste function. The t-test was used for analyzing continuous variables, and the chi-square test for categorical data. Clinical staging and medication status were included in a model analyzed using analysis of variances. RESULTS: MG patients showed significantly lower olfactory (p<0.001) and gustatory scores (p<0.001) than the healthy controls. In addition, olfactory loss correlated with the severity of the disease. Medications for MG did not influence these results. CONCLUSION: This study replicates the olfactory dysfunction found elsewhere in MG. Further, gustatory dysfunction, an activity unrelated to muscle strength, was also unveiled. Medications used for treating MG must not be blamed for the chemosensory dysfunction found in this neurological disorder. PMID- 26148932 TI - Temporal profile of M1 and M2 responses in the hippocampus following early 24h of neurotrauma. AB - Traumatic brain injury (TBI) elicits complex inflammatory assets (M1 and M2 responses) in the brain that include the expression of various cytokines/chemokines and the recruitment of blood cells, contributing secondary injury cascades (SIC), and also recovery processes. The modulation of such inflammatory assets might be a therapeutic option following TBI. The present study assesses a temporal profile of various molecular markers of M1 and M2 response in the hippocampus after TBI. Following a unilateral controlled cortical impact (CCI) on young rats, hippocampal tissues of each brain were harvested at 2, 4, 6, 10, and 24h post trauma. Including shams (craniotomy only), half of the rats were assessed for gene expression and half for the protein of various markers for M1 [interferon-gamma (IFNgamma), tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-1-beta (IL-1beta), and IL-6] and M2 [IL-4, IL-10, IL 13, arginase 1 (Arg1), YM1, FIZZ1, and mannose receptor C-1 (MRC1)] responses. Analysis revealed that molecular markers of M1 and M2 responses have heterogeneous injury effects in the hippocampus and that "time-post-injury" is an important factor in determining inflammation status. With the heterogeneous gene expression of pro-inflammatory cytokines, M1 response was significantly elevated at 2h and declined at 24h after TBI, however, their levels remained higher than the sham rats. Except IFNgamma, proteins of M1 cytokines were significantly elevated in the first 24h, and peaked between 2-6h [TNFalpha (2h), IL-1beta (6h), and IL-6 (4-6h)]. With the heterogeneous relative gene expression of Arg1, YM1, FIZZ1, and MRC1, levels of M2 cytokines were peaked at 24h post TBI. IL-10 and IL 13 expression appeared biphasic in the first 24h. Protein values of IL-4 and IL 13 peaked at 24h and IL-10 at 6h post injury. Results suggest that the M1 response rises rapidly after injury and overpowers the initial, comparatively smaller, or transient M2 response. A treatment that can modulate inflammation, reduce SIC, and improve recovery should be initiated early (within 10h) after TBI. PMID- 26148934 TI - Inverse association between yerba mate consumption and idiopathic Parkinson's disease. A case-control study. AB - Yerba mate tea is a very common beverage in some countries of South America. We conducted a case-control study on an individual basis using hospital records to investigate the association between Parkinson's disease (PD) and yerba mate intake. A case was defined as an age of >= 40 years with >= 1 year of PD. Each case was individually matched by two controls. Exposure was measured by yerba mate consumption, coffee, tea, and alcohol intake and smoking status. The sample consisted of 223 PD patients (mean age 68 years and mean disease duration 7.3 years) and 406 controls. There was an inverse association between yerba mate "bombilla" consumption and PD (OR 0.64, 95% CI: 0.54-0.76, p=0.00001). A multivariate analysis with a logistic regression adjusted by sex, alcohol intake and smoking provided the following results: yerba mate (OR 0.63, 95% CI: 0.53 0.76), tea (OR 0.60, 95% CI: 0.42-0.86), coffee (OR 0.51, 95% CI: 0.35-0.73). We found an inverse association between yerba mate consumption and PD. These results led us to hypothesize that yerba mate may have a potential protective role in the development of PD. PMID- 26148935 TI - Claudin-3 is required for modulation of paracellular permeability by TNF-alpha through ERK1/2/slug signaling axis in submandibular gland. AB - TNF-alpha plays an important role in the pathogenesis of salivary inflammatory diseases. Salivary dysfunction, which leads to impaired saliva secretion, can be caused by TNF-alpha-induced disrupted epithelial barrier. However, the signaling mechanism involved in TNF-alpha-modulated tight junction barrier in salivary gland remains unclear. Here, we found that TNF-alpha reduced transepithelial resistance (TER) and increased FITC-dextran flux in a rat submandibular cell line SMG-C6. Claudin (Cln)-3 was selectively downregulated and disrupted by TNF-alpha, whereas Cln-1, Cln-4, and beta-catenin were not affected. Overexpression of Cln-3 retained and Cln-3 knockdown abolished the TNF-alpha-induced alterations. Moreover, TNF-alpha increased extracellular signal-regulated kinase (ERK1/2) phosphorylation and the expression of transcriptional factor slug. ERK1/2 kinase inhibitor PD98059 abrogated TNF-alpha-induced increase in paracellular permeability, alterations of Cln-3, and elevation of slug. Overexpression of slug decreased and slug knockdown increased Cln-3 expression. In addition, slug bind to the E-box elements of Cln-3 promoter in TNF-alpha-treated cells, and this response was blocked by PD98059. Furthermore, TNF-alpha decreased Cln-3 expression and increased slug content in cultured human submandibular gland. Taken together, our data suggest that Cln-3 plays a vital role in TNF-alpha modulated paracellular permeability in submandibular epithelium and ERK1/2/slug signaling axis is involved in alteration of Cln-3 redistribution and downregulation. PMID- 26148936 TI - Aldosterone-induced cardiomyocyte growth, and fibroblast migration and proliferation are mediated by TRAF3IP2. AB - Sustained activation of the Renin-Angiotensin-Aldosterone System (RAAS) contributes to the pathogenesis of heart failure. Aldosterone (Aldo) is known to induce both myocardial hypertrophy and fibrosis through oxidative stress and proinflammatory pathways. Here we have investigated whether Aldo-mediated cardiomycocyte hypertrophy is dependent on TRAF3IP2, an upstream regulator of IKK and JNK. We also investigated whether the pro-mitogenic and pro-migratory effects of Aldo on cardiac fibroblasts are also mediated by TRAF3IP2. Aldo induced both superoxide and hydrogen peroxide in isolated adult mouse cardiomyocytes (CM), and upregulated TRAF3IP2 expression in part via the mineralocorticoid receptor and oxidative stress. Silencing TRAF3IP2 blunted Aldo-induced IKKbeta, p65, JNK, and c-Jun activation, IL-18, IL-6 and CT-1 upregulation, and cardiomyocyte hypertrophy. In isolated adult mouse cardiac fibroblasts (CF), Aldo stimulated TRAF3IP2-dependent IL-18 and IL-6 production, CTGF, collagen I and III expression, MMP2 activation, and proliferation and migration. These in vitro results suggest that TRAF3IP2 may play a causal role in Aldo-induced adverse cardiac remodeling in vivo, and identify TRAF3IP2 as a potential therapeutic target in hypertensive heart disease. PMID- 26148937 TI - Proteomics profiling of cholangiocarcinoma exosomes: A potential role of oncogenic protein transferring in cancer progression. AB - Cholangiocarcinoma (CCA), a common primary malignant tumor of bile duct epithelia, is highly prevalent in Asian countries and unresponsive to chemotherapeutic drugs. Thus, a newly recognized biological entity for early diagnosis and treatment is highly needed. Exosomes are small membrane bound vesicles found in body fluids and released by most cell types including cancer cells. The vesicles contain specific subset of proteins and nucleic acids corresponding to cell types and play essential roles in pathophysiological processes. The present study aimed to assess the protein profiles of CCA-derived exosomes and their potential roles. We have isolated exosomes from CCA cells namely KKU-M213 and KKU-100 derived from Thai patients and their roles were investigated by incubation with normal human cholangiocyte (H69) cells. Exosomes were internalized into H69 cells and had no effects on viability or proliferation of the host cells. Interestingly, the exosomes from KKU-M213 cells only induced migration and invasion of H69 cells. Proteomic analysis of the exosomes from KKU M213 cells disclosed multiple cancer related proteins that are not present in H69 exosomes. Consistent with the protein profile, treatment with KKU-M213 exosomes induced beta-catenin and reduced E-cadherin expressions in H69 cells. Collectively, our results suggest that a direct cell-to-cell transfer of oncogenic proteins via exosomal pathway may be a novel mechanism for CCA progression and metastasis. PMID- 26148938 TI - From Silylone to an Isolable Monomeric Silicon Disulfide Complex. AB - The synthesis and characterization of the first bis-N-heterocyclic carbene stabilized monomeric silicon disulfide (bis-NHC)SiS2 2 (bis-NHC=H2 C[{NC(H)C(H)N(Dipp)}C:]2 , Dipp=2,6-iPr2 C6 H3 ) is reported. Compound 2 is prepared in 89 % yield from the reaction of the zero-valent silicon complex ('silylone') 1 [(bis-NHC)Si] with elemental sulfur. Compound 2 can react with GaCl3 in acetonitrile to give the corresponding (bis-NHC)Si(S)S->GaCl3 Lewis acid base adduct 3 in 91 % yield. Compound 3 is also accessible through the reaction of the unprecedented silylone-GaCl3 adduct [(bis-NHC)Si->GaCl3 ] 4 with elemental sulfur. Compounds 2, 3, and 4 could be isolated and characterized by elemental analyses, HR-MS, IR, (13) C- and (29) Si-NMR spectroscopy. The structures of 3 and 4 could be determined by single-crystal X-ray diffraction analyses. DFT derived bonding analyses of 2 and 3 exhibited highly polar Si-S bonds with moderate ppi -ppi bonding character. PMID- 26148939 TI - Feasibility, safety, and outcome of very early enteral nutrition in critically ill patients: Results of an observational study. PMID- 26148940 TI - Marital Status as a Moderating Factor in the Process of Disablement. AB - OBJECTIVE: To test current marital status as a moderator on the influence of depressive symptoms and chronic conditions on subsequent functional limitations. METHOD: Data come from the Health and Retirement Study (HRS; 1998-2010). Hierarchal linear modeling models tested differences in functional limitations among a sample of 20,215 people. RESULTS: At baseline, married people suffered from fewer subsequent functional limitations than the unmarried. Moreover, limited evidence suggests the influence of depressive symptoms was greater for the married than the unmarried; however, the influence of chronic conditions was consistently attenuated for married people. Accounting for differences in prior health, work, socioeconomic status, and health behaviors did not explain the moderating influence of marital status on the associations between symptoms of depression and chronic conditions with functional limitations. DISCUSSION: This research highlights the need to identify potential modifiers that may help disrupt the process of disablement among both the married and the unmarried alike. PMID- 26148942 TI - Childhood Circumstances and Mid-Life Functional Mobility. AB - OBJECTIVES: We examine the cumulative long-term role of childhood health and socioeconomic status in affecting functional health at ages 50 to 59. METHOD: Data on 2,233 respondents to The Irish Longitudinal Study of Aging (TILDA) are used to examine functional health measured by the timed-up-and-go (TUG) test of lower-body mobility. We examine the association of father's education, childhood rural residence, and childhood self-evaluated health with TUG and examine respondent's education, adult health behaviors, measured health, and cognition as mediators of the association of childhood characteristics and TUG. RESULTS: Father's education, rural residence, childhood health, and education are associated with TUG times at ages 50 to 59. While health behaviors mediate most of the rural residence and education associations, the association with childhood self-evaluated health is direct. DISCUSSION: Early life circumstances play substantial direct and indirect roles in molding functional level in late mid life. PMID- 26148941 TI - Aging Prisoners in Switzerland: An analysis of Their Health Care Utilization. AB - OBJECTIVE: This study assessed health care utilization of aging prisoners and compared it with that of younger prisoners. METHOD: Health care utilization comprised visits to general practitioners (GPs), nurses, and mental health professionals (MHPs) for a period of 6 months. Using retrospective study design, data were extracted from medical records of 190 older prisoners (50 years and older) and 190 younger inmates (18-49 years). Age group was a dichotomous predictor variable with type of sentencing and time spent in prison as covariates. Descriptive statistics and generalized linear mixed models (GLMMs) were performed. RESULTS: For each of the three outcome variables, two GLMMs were constructed. The first model only included age group as the predictor variable (3 * Unadjusted models). The second included the two covariates in addition to the predictor variable (3 * Adjusted model). Results from the adjusted model indicate that visits to GPs significantly differed between the two age groups (p = .022). Older prisoners visited GPs 1.43 times more often than younger prisoners over the 6-month period (adjusted risk ratio [RR] = 1.43, 95% confidence interval [CI] = [1.05, 1.94]). The finding for visits to nurses was not statistically significant (p = .080). However, older prisoners visited nurses 1.36 times more frequently (adjusted RR = 1.36, 95% CI = [0.96, 1.91]). Finally, older prisoners visited MHPs 1.24 times more often than younger prisoners (adjusted RR = 1.24, 95% CI = [.95, 1.61]) and this finding was also not statistically significant (p = .11). DISCUSSION: Study findings underline that older prisoners utilized health care more often than younger prisoners although in most models the finding did not reach statistical significance. The prison system must develop solutions to address the needs of an aging population, particularly those with physical and mental health problems. PMID- 26148943 TI - Predictors of Long-Term Care Facility Residents' Self-Reported Quality of Life With Individual and Facility Characteristics in Canada. AB - OBJECTIVE: Identify predictors of long-term care (LTC) facility residents' self reported quality of life (QoL). METHOD: QoL of a convenience sample of 928 residents from 48 volunteer LTC facilities across six Canadian provinces was assessed using the inter-Resident Assessment Instrument (interRAI) Self-Report Nursing Home Quality of Life Survey. Multivariate regression models were used to identify predictors. RESULTS: In logistic regression modeling, residents who were religious and socially engaged, had a positive global disposition, or resided in rural, private, or municipal facilities were less likely to report low QoL. Those with post-secondary education and who were dependent on activities of daily living were more likely to report low QoL. These factors, except for religiosity and residence in municipal facilities, were significant in generalized estimating equation (GEE) modeling. DISCUSSION: QoL is significantly associated with select resident and LTC facility characteristics with implications for improving residents' QoL and LTC facility programming, and guiding future research and social policy development. PMID- 26148944 TI - Is Intelligence in Early Adulthood Associated With Midlife Physical Performance Among Danish Males? AB - OBJECTIVE: Insights into the causes of variances in physical performance are important to prevent mobility limitations in old age. We examined associations between intelligence in early adulthood and midlife physical performance. METHOD: Data from the Copenhagen Aging and Midlife Biobank were analyzed using linear regression. In total, 2,848 male cohort members had intelligence scores from conscription and physical performance measures from midlife. RESULTS: In adjusted models, a 1 SD increase in intelligence resulted in 1.10 more chair-rises (p < .001), a 1.03 cm higher jump (p < .001), a 3.69% smaller balance area (p < .001), a 0.71 kg increase in handgrip strength (p < .001), and a 5.03 N increase in back force (p < .001). Results for flexibility and abdominal force were not significant. DISCUSSION: Public health interventions should focus on addressing people with different cognitive abilities and bear in mind that prevention of mobility limitations might need to start early in life. PMID- 26148945 TI - Scaffolds and tissue regeneration: An overview of the functional properties of selected organic tissues. AB - Tissue engineering plays a significant role both in the re-establishment of functions and regeneration of organic tissues. Success in manufacturing projects for biological scaffolds, for the purpose of tissue regeneration, is conditioned by the selection of parameters such as the biomaterial, the device architecture, and the specificities of the cells making up the organic tissue to create, in vivo, a microenvironment that preserves and further enhances the proliferation of a specific cell phenotype. To support this approach, we have screened scientific publications that show biomedical applications of scaffolds, biomechanical, morphological, biochemical, and hemodynamic characteristics of the target organic tissues, and the possible interactions between different cell matrices and biological scaffolds. This review article provides an overview on the biomedical application of scaffolds and on the characteristics of the (bio)materials commonly used for manufacturing these biological devices used in tissue engineering, taking into consideration the cellular specificity of the target tissue. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1483-1494, 2016. PMID- 26148947 TI - Integrating a Parenting Intervention With Routine Primary Health Care: A Cluster Randomized Trial. AB - OBJECTIVE: More than 200 million children globally do not attain their developmental potential. We hypothesized that a parent training program could be integrated into primary health center visits and benefit child development. METHODS: We conducted a cluster randomized trial in the Caribbean (Jamaica, Antigua, and St Lucia). Fifteen centers were randomly assigned to the control (n = 250 mother-child pairs) and 14 to the intervention (n = 251 mother-child pairs) groups. Participants were recruited at the 6- to 8-week child health visit. The intervention used group delivery at 5 routine visits from age 3 to 18 months and comprised short films of child development messages, which were shown in the waiting area; discussion and demonstration led by community health workers; and mothers' practice of activities. Nurses distributed message cards and a few play materials. Primary outcomes were child cognition, language, and hand-eye coordination and secondary outcomes were caregiver knowledge, practices, maternal depression, and child growth, measured after the 18-month visit. RESULTS: Eight five percent of enrolled children were tested (control = 210, intervention = 216). Loss did not differ by group. Multilevel analyses showed significant benefits for cognitive development (3.09 points; 95% confidence interval: 1.31 to 4.87 points; effect size: 0.3 SDs). There were no other child benefits. There was a significant benefit to parenting knowledge (treatment effect: 1.59; 95% confidence interval: 1.01 to 2.17; effect size: 0.4). CONCLUSIONS: An innovative parenting intervention, requiring no additional clinic staff or mothers' time, was integrated into health services, with benefits to child cognitive development and parent knowledge. This is a promising strategy that merits further evaluation at scale. PMID- 26148948 TI - Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus. AB - Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a recently described glucose transporter 1-negative multifocal vascular disorder with significant morbidity and mortality. However, data are lacking on the clinical spectrum, long-term prognosis, and treatment of MLT. It is often confused with multifocal infantile hemangioma, but the conditions must be differentiated for appropriate assessment and therapeutic management. Treatments for MLT have been disappointing, and the treatments classically used for infantile hemangioma are often ineffective. We report 3 newborn cases featuring various clinical and biological phenotypes of MLT: 1 patient had severe brain involvement and died early; another had no thrombocytopenia; and the third had nearly no skin involvement. Histologically, all were negative for glucose transporter 1 and positive for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 or D2-40 (~38-kDa O-linked transmembrane sialoglycoprotein podoplanin). Two cases with severe gastrointestinal bleeding were treated with sirolimus 0.1 mg/k per day, which was efficient after the first month of treatment. MLT clinically presents in various forms, and when complicated by widespread or severe extracutaneous involvement, initial aggressive therapeutic intervention is justified. The pathogenesis of MLT remains unclear, but lymphatic differentiation is widely acknowledged. Because of its antiangiogenic properties, including anti-lymphangiogenesis, sirolimus offers an adequate and targeted therapeutic approach for MLT. PMID- 26148949 TI - Balancing the Tension Between Hyperoxia Prevention and Alarm Fatigue in the NICU. AB - BACKGROUND: After the implementation of narrowed oxygen saturation alarms, alarm frequency increased in the C.S. Mott Children's Hospital NICU which could have a negative impact on patient safety. The Joint Commission on the Accreditation of Healthcare Organizations issued a Sentinel Event Alert for hospitals in 2013 to improve alarm safety, resulting in a 2014 National Patient Safety Goal requiring institutional policies and procedures to be in place to manage alarms. METHODS: A multidisciplinary improvement team developed an alarm management bundle applying strategies to decrease alarm frequency, which included evaluating existing strategies and developing patient care-based and systems-based interventions. The total number of delivered and detected saturation alarms and high saturation alarms and the total time spent within a targeted saturation range were quantitatively tracked. Nursing morale was assessed qualitatively. RESULTS: SpO2 alarms per monitored patient-day increased from 78 to 105 after the narrowing of alarm limits. Modification of the high saturation alarm algorithm substantially decreased the delivery and escalation of high pulse oxygen saturation (SpO2) alarms. During a pilot period, using histogram technology to individually customize alarm limits resulted in increased time spent within the targeted saturation range and fewer alarms per day. Qualitatively, nurses reported improved satisfaction when not assigned >1 infant with frequent alarms, as identified by an alarm frequency tool. CONCLUSIONS: Alarm fatigue may detrimentally affect patient care and safety. Alarm management strategies should coincide with oxygen management within a NICU, especially in single-patient-bed units. PMID- 26148950 TI - Pediatric Psychopharmacology for Treatment of ADHD, Depression, and Anxiety. AB - The pediatric practitioner is often the first point-of-contact for children and adolescents suffering from mental illness. Part of the treatment planning for psychiatric diagnoses includes consideration of medication. Attention deficit/hyperactivity disorder, one of the most common diagnoses, is very responsive to stimulant medications; for children who are unable to tolerate stimulants or who do not achieve satisfactory symptom management, central alpha agonists and atomoxetine are effective and generally well-tolerated alternative or augmentative agents. Depression and anxiety disorders are also frequently encountered in the pediatric office setting. The use of selective serotonin reuptake inhibitors is considered first-line psychopharmacology for depression and anxiety symptoms. Despite concerns for suicidal ideation related to this medication class, the benefits typically outweigh the risks. This review provides basic clinical pharmacology of stimulant and nonstimulant attention deficit/hyperactivity disorder medications and selective serotonin reuptake inhibitors intended to serve as a primer for the general pediatrician. PMID- 26148951 TI - The Dying Child in Seventeenth-Century England. PMID- 26148952 TI - Children and Armed Conflict. PMID- 26148953 TI - Hospitalizations of Children With Pulmonary Hypertension: Implications for Improving Care. PMID- 26148954 TI - Identifying Priorities for Mental Health Interventions in War-Affected Youth: A Longitudinal Study. AB - BACKGROUND: War-affected youth often suffer from multiple co-occurring mental health problems. These youth often live in low-resource settings where it may be infeasible to provide mental health services that simultaneously address all of these co-occurring mental health issues. It is therefore important to identify the areas where targeted interventions would do the most good. METHODS: This analysis uses observational data from 3 waves of a longitudinal study on mental health in a sample of 529 war-affected youth (24.2% female; ages 10-17 at T1, 2002) in Sierra Leone. We regressed 4 mental health outcomes at T3 (2008) on internalizing (depression/anxiety) and externalizing (hostility/aggression) problems and prosocial attitudes/behaviors and community variables at T2 (2004) controlling for demographics, war exposures, and previous mental health scores at T1, allowing us to assess the relative impact of potential mental health intervention targets in shaping mental health outcomes over time. RESULTS: Controlling for baseline covariates at T1 and all other exposures/potential intervention targets at T2, we observed a significant association between internalizing problems at T2 and 3 of the 4 outcomes at T3: internalizing (beta = 0.27, 95% confidence interval [CI]: 0.11-0.42), prosocial attitudes (beta = 0.20, 95% CI: -0.33 to -0.07) and posttraumatic stress symptoms (beta = 0.22, 95% CI: 0.02-0.43). No other potential intervention target had similar substantial effects. CONCLUSIONS: Reductions in internalizing may have multiple benefits for other mental health outcomes at a later point in time, even after controlling for confounding variables. PMID- 26148955 TI - Statewide Medicaid Enhanced Prenatal Care Programs and Infant Mortality. AB - OBJECTIVE: To evaluate whether participation in a statewide enhanced prenatal and postnatal care program, the Maternal Infant Health Program (MIHP), reduced infant mortality risk. METHODS: Data included birth and death records, Medicaid claims, and program participation. The study population consisted of Medicaid-insured singleton infants born between January 1, 2009, and December 31, 2012, in Michigan (n = 248 059). The MIHP participants were propensity score-matched with nonparticipants based on demographics, previous pregnancies, socioeconomic status, and chronic disease. Infant mortality, neonatal mortality, and postneonatal mortality analyses were presented by race. RESULTS: Infants with any MIHP participation had reduced odds of death in the first year of life compared with matched nonparticipants (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.63-0.84). Infant death odds were reduced both among black infants (OR 0.71, 95% CI 0.58-0.87) and infants of other races (OR 0.74, 95% CI 0.61-0.91). Neonatal death (OR 0.70, 95% CI 0.57-0.86) and postneonatal death odds (OR 0.78, 95% CI 0.63-0.96) were also reduced. Enrollment and screening in MIHP by the end of the second pregnancy trimester and at least 3 additional prenatal MIHP contacts reduced infant mortality odds further (OR 0.70, 95% CI 0.58-0.85; neonatal: OR 0.67, 95% CI 0.51-0.89; postneonatal: OR 0.74, 95% CI 0.56-0.98). CONCLUSIONS: A state Medicaid-sponsored population-based home-visitation program can be a successful approach to reduce mortality risk in a diverse, disadvantaged population. A likely mechanism is the reduction in the risk of adverse birth outcomes, consistent with previous findings on the effects of the program. PMID- 26148956 TI - Trends in Hospitalization for Pediatric Pulmonary Hypertension. AB - BACKGROUND AND OBJECTIVES: Pulmonary hypertension (PH) has been associated with substantial morbidity and mortality in children, but existing analyses of inpatient care are limited to small single-institution series or focused registries representative of selected patient subgroups. We examined US national data on pediatric PH hospitalizations to determine trends in volume, demographics, procedures performed during admission, and resource utilization. METHODS: Retrospective cohort study using a national administrative database of pediatric hospital discharges: the Kids' Inpatient Database. RESULTS: Children with PH accounted for 0.13% of the 43 million pediatric hospitalizations in the United States between 1997 and 2012, and discharges demonstrated an increasing trend over the study period (P < .0001). Cumulative, inflation-adjusted national hospital charges for PH hospitalizations rose (P = .0003) from $926 million in 1997 to $3.12 billion in 2012. Patients with PH without associated congenital heart disease (CHD) comprised an increasing and majority (56.4%) proportion over the study period (P < .0001), children without associated CHD admitted at urban teaching hospitals comprised the fastest-growing subgroup. In-hospital, all-cause mortality was high (5.9%) in children with PH, but demonstrated a decreasing trend (P < .0001). CONCLUSIONS: Morbidity and mortality of pediatric PH continue to represent substantial and growing health care burdens. Shifts in case mix toward PH not associated with CHD, toward noncardiac procedures, and toward care in urban teaching hospitals will increase pressure to manage resource utilization in this small but growing patient group and to improve expertise and define excellence in PH care across a wide range of clinical settings. PMID- 26148957 TI - Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report. AB - Management of patients with complex vascular anomalies (VAs) is often associated with significant morbidity and mortality because of the lack of effective treatment modalities that may lead to significant improvement of the disease and/or healing. Recently, reports of treatment of patients with complex VAs with sirolimus revealed encouraging results. Sirolimus inhibits the mammalian target of rapamycin, which acts as a master switch of numerous cellular processes. We report a successful use of sirolimus for the treatment of a patient with a complex CLVM of the trunk and the right lower extremity believed to be untreatable. Our patient had 44 hospitalizations during the 10-year period, with various unsuccessful treatments and continuous deterioration of his clinical condition, ending up in a wheelchair. His condition reversed to normal everyday activities 9 months after initiation of sirolimus therapy. We conclude that sirolimus is a very promising therapeutic option for children with complex VAs of capillary-lymphatico-venous type. PMID- 26148958 TI - HC-HA/PTX3 Purified From Amniotic Membrane Promotes BMP Signaling in Limbal Niche Cells to Maintain Quiescence of Limbal Epithelial Progenitor/Stem Cells. AB - To explore how limbal niche cells (LNCs) may control quiescence, self-renewal, and corneal epithelial lineage commitment/differentiation of limbal epithelial progenitor/stem cells (LEPCs), we have established an in vitro sphere assay by reunion between the two cell types in three-dimensional Matrigel. The resultant sphere exhibits inhibition of corneal epithelial lineage commitment/differentiation and marked clonal growth of LEPCs, of which the latter is correlated with activation of canonical Wnt signaling. Herein, we have created a similar reunion assay in immobilized heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3), which is purified from amniotic membrane (AM) and consists of a complex formed by hyaluronic covalently linked to heavy chain 1 of inter-alpha inhibitor and noncovalently linked to pentraxin 3. The resultant spheres exhibited similar suppression of corneal epithelial lineage commitment/differentiation but upregulation of quiescence markers including nuclear translocation of Bmi-1, and negligible clonal growth of LEPCs. This outcome was correlated with the suppression of canonical Wnt but activation of noncanonical (Planar cell polarity) Wnt signaling as well as BMP signaling in both LEPCs and LNCs. The activation of BMP signaling in LNCs was pivotal because nuclear translocation of pSmad1/5/8 was prohibited in hLEPCs when reunioned with mLNCs of conditionally deleted Bmpr1a;Acvr1(DCKO) mice. Furthermore, ablation of BMP signaling in LEPCs led to upregulation of cell cycle genes, downregulation of Bmi-1, nuclear exclusion of phosphorylated Bmi-1, and marked promotion of the clonal growth of LEPCs. Hence, HC-HA/PTX3 uniquely upregulates BMP signaling in LNCs which leads to BMP signaling in LEPCs to achieve quiescence, helping explain how AM transplantation is clinically useful to be used as a matrix for ex vivo expansion of LEPCs and to treat corneal blindness caused by limbal stem cells deficiency. PMID- 26148959 TI - Negishi Cross-Coupling Is Compatible with a Reactive B-Cl Bond: Development of a Versatile Late-Stage Functionalization of 1,2-Azaborines and Its Application to the Synthesis of New BN Isosteres of Naphthalene and Indenyl. AB - The compatibility of the Negishi cross-coupling reaction with the versatile B-Cl functionality has been demonstrated in the context of late-stage functionalization of 1,2-azaborines. Alkyl-, aryl-, and alkenylzinc reagents have been utilized for the functionalization of the triply orthogonal precursor 3 bromo-1-(tert-butyldimethylsilyl)-2-chloro-1,2-dihydro-1,2-azaborine (2) to furnish new 2,3-substituted monocyclic 1,2-azaborines. This methodology has enabled the synthesis of previously elusive BN-naphthalene and BN-indenyl structures from a common intermediate. PMID- 26148960 TI - Occupational exposure to nanoparticles at commercial photocopy centers. AB - Photocopiers emit high levels of nanoparticles (PM0.1). To-date little is known of physicochemical composition of PM0.1 in real workplace settings. Here we perform a comprehensive physicochemical and morphological characterization of PM0.1 and raw materials (toners and paper) at eight commercial photocopy centers that use color and monochrome photocopiers over the course of a full week. We document high PM0.1 exposures with complex composition and several ENM in toners and PM0.1. Daily geometric mean PM0.1 concentrations ranged from 3700 to 34000 particles/cubic-centimeter (particles/cm(3)) (GSD 1.4-3.3), up to 12 times greater than background, with transient peaks >1.4 million particles/cm(3). PM0.1 contained 6-63% organic carbon, <1% elemental carbon, and 2-8% metals, including iron, zinc, titania, chromium, nickel and manganese, typically in the <0.01-1% range, and in agreement with toner composition. These findings document widespread ENM in toner formulations and high nanoparticle exposures are an industry-wide phenomenon. It further calls attention to the need to substantially redesign the interface of this technology with workers and consumers. PMID- 26148961 TI - Soil retention of hexavalent chromium released from construction and demolition waste in a road-base-application scenario. AB - We investigated the retention of Cr(VI) in three subsoils with low organic matter content in laboratory experiments at concentration levels relevant to represent leachates from construction and demolition waste (C&DW) reused as unbound material in road construction. The retention mechanism appeared to be reduction and subsequent precipitation as Cr(III) on the soil. The reduction process was slow and in several experiments it was still proceeding at the end of the six month experimental period. The overall retention reaction fit well with a second order reaction governed by actual Cr(VI) concentration and reduction capacity of the soil. The experimentally determined reduction capacities and second-order kinetic parameters were used to model, for a 100-year period, the one-dimensional migration of Cr(VI) in the subsoil under a layer of C&DW. The resulting Cr(VI) concentration would be negligible below 7-70 cm depth. However, in rigid climates and with high water infiltration through the road pavement, the reduction reaction could be so slow that Cr(VI) might migrate as deep as 200 cm under the road. The reaction parameters and the model can form the basis for systematically assessing under which scenarios Cr(VI) from C&DW could lead to an environmental issue for ground- and receiving surface waters. PMID- 26148962 TI - Collision cross section calibrants for negative ion mode traveling wave ion mobility-mass spectrometry. AB - Unlike traditional drift-tube ion mobility-mass spectrometry, traveling-wave ion mobility-mass spectrometry typically requires calibration in order to generate collision cross section (CCS) values. Although this has received a significant amount of attention for positive-ion mode analysis, little attention has been paid for CCS calibration in negative ion mode. Here, we provide drift-tube CCS values for [M - H](-) ions of two calibrant series, polyalanine and polymalic acid, and evaluate both types of calibrants in terms of the accuracy and precision of the traveling-wave ion mobility CCS values that they produce. PMID- 26148964 TI - ? PMID- 26148963 TI - Likelihood-based inference for discretely observed birth-death-shift processes, with applications to evolution of mobile genetic elements. AB - Continuous-time birth-death-shift (BDS) processes are frequently used in stochastic modeling, with many applications in ecology and epidemiology. In particular, such processes can model evolutionary dynamics of transposable elements-important genetic markers in molecular epidemiology. Estimation of the effects of individual covariates on the birth, death, and shift rates of the process can be accomplished by analyzing patient data, but inferring these rates in a discretely and unevenly observed setting presents computational challenges. We propose a multi-type branching process approximation to BDS processes and develop a corresponding expectation maximization algorithm, where we use spectral techniques to reduce calculation of expected sufficient statistics to low dimensional integration. These techniques yield an efficient and robust optimization routine for inferring the rates of the BDS process, and apply broadly to multi-type branching processes whose rates can depend on many covariates. After rigorously testing our methodology in simulation studies, we apply our method to study intrapatient time evolution of IS6110 transposable element, a genetic marker frequently used during estimation of epidemiological clusters of Mycobacterium tuberculosis infections. PMID- 26148965 TI - Virulence and antimicrobial resistance determinants of verotoxigenic Escherichia coli (VTEC) and of multidrug-resistant E. coli from foods of animal origin illegally imported to the EU by flight passengers. AB - The aim of this study was to reveal phenotype/genotype characteristics of verotoxigenic Escherichia coli (VTEC) and multidrug resistant E. coli in food products of animal origin confiscated as illegal import at Austrian, German and Slovenian airports. VTEC isolates were obtained by using ISO guidelines 16654:2001 for O157 VTEC or ISO/ TS13136:2012 for non-O157 VTEC, with additional use of the RIDASCREEN(r) Verotoxin immunoassay. The testing of 1526 samples resulted in 15 VTEC isolates (1.0%) primarily isolated from hard cheese from Turkey and Balkan countries. Genotyping for virulence by using a miniaturized microarray identified a wide range of virulence determinants. One VTEC isolate (O26:H46) possessing intimin (eae) and all other essential genes of Locus of Enterocyte Effacement (LEE) was designated as enterohemorrhagic E. coli (EHEC). None of the other VTEC strains belonged to serogroups O157, O145, O111, O104 or O103. VTEC strains harbored either stx(1) (variants stx1(a) or stx(1c)) or st(x2) (variants stx(2a), stx(2b), stx(2a/d) or stx(2c/d)) genes. Pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) demonstrated high genetic diversity and identified three new sequence types (STs): 4505, 4506 and 4507. Food samples collected from the Vienna airport were also tested for E. coli quantities using the ISO 16649:2001, and for detection of multidrug resistant phenotypes and genotypes. The resulting 113 commensal E. coli isolates were first tested in a pre-screening against 6 selected antimicrobials to demonstrate multidrug resistance. The resulting 14 multidrug resistant (MDR) E. coli isolates, representing 0.9% of the samples, were subjected to further resistance phenotyping and to microarray analyses targeting genetic markers of antimicrobial resistance and virulence. Genotyping revealed various combinations of resistance determinants as well as the presence of class 1, class 2 integrons. The isolates harbored 6 to 11 antibiotic resistance genes as well as 1 to 14 virulence genes. In this panel of 14 MDR E. coli two strains proved to carry CTX-M type ESBLs, and one single isolate was identified as enteropathogenic E. coli (EPEC). In general, isolates carrying a high number of resistance determinants had lower number of virulence genes and vice versa. In conclusion, this first pilot study on the prevalence of VTEC and of MDR/ESBL E. coli in illegally imported food products of animal origin suggests that these strains could represent reservoirs for dissemination of potentially new types of pathogenic and MDR E. coli in Europe. PMID- 26148966 TI - Liver Volume Restoration and Hepatic Microarchitecture in Small-for-Size Syndrome. AB - BACKGROUND: We investigated preoperative parameters that could work as markers of liver regeneration (LR), and tried to create an algorithm for therapeutic decision-making, looking at the clinical setting of post-hepatectomy liver failure (PHLF) after major liver resection for malignancies (LRM) and of the small-for-size syndrome (SFSS) after adult-to-adult living related liver transplantation (LRLT), considering PHLF and SFSS a single clinical entity. MATERIAL AND METHODS: The clinical data of 2 series of 10 consecutive patients who experienced liver-specific complications after LRLT or LRM between 2008 and 2013 were analyzed. LR was evaluated by multidetector computed tomography (MDCT) and hepatic parenchymal findings with specific re-examinations of liver biopsies. The analysis was done according to demographics, tumor characteristics, and postoperative complications occurring within 90 days of surgery and codified within the Clavien classification. RESULTS: A total of 13 cases of SFSS occurred in 8 LRLT recipients (61.5%) and in 5 patients after LRM (38.5%). The incidence of SFSS was significantly associated with a greater spleen volume/future remnant liver volume ratio (1.08+/-0.5; P=0.02) and a reduced number of hepatic tumors (0.58+/-0.6; P=0.04). A greater degree of LR was not associated with a lesser likelihood of developing SFSS (P=0.31). SFSS incidence and re-examination of post operative liver biopsies differed according to the evidence of focal endothelial denudation in the portal vein and centrilobular hepatocanalicular cholestasis. We found an association between SFSS incidence and the immunohistochemical overexpression of cytological proliferation marker Ki-67 (29.3+/-29.8%; P=0.007), which was a significant predictor of poor post-operative survival (OR=1.12, C.I.: 1.013; 1.242). CONCLUSIONS: SFSS is a rare but dangerous clinical entity characterized by anarchic hepatic regeneration. We suggest focusing on early diagnosis in order to establish non-surgical modulation of the portal inflow, in conjunction with optimization of medical management. PMID- 26148967 TI - Computed tomography evaluation of hip geometry restoration after total hip resurfacing. AB - BACKGROUND: Anatomic reconstruction of the hip is among the main requirements for hip arthroplasty to be successful. Resurfacing arthroplasty may improve replication of the native joint geometry but has been evaluated only using standard radiographs. We therefore performed a computed tomography (CT) study to assess restoration of hip geometry after total hip resurfacing (HR), comparatively with the non-operated side. HYPOTHESIS: HR does not change native extra-medullary hip geometry by more than 5mm and/or 5 degrees . PATIENTS AND METHODS: CT was used to evaluate unilateral HR in 75 patients with a mean age of 52.2years (range, 22-67years). The normal non-operated side served as the control in each patient. Mean follow-up was 2.5years (range, 1.9-3.1years). The primary evaluation criteria were femoral offset (FO) and femoral neck anteversion (FNA) and the secondary criteria were cup inclination angle, cup anteversion angle, and lower-limb length. RESULTS: FO showed a non-significant decrease (mean, -2.2mm; range, -4.5 to +3.7mm). FNA was preserved, with a difference of less than 2 degrees at last follow-up versus the preoperative value. Cup measurements showed a mean anteversion angle of 24.8 degrees (0.9-48.6) and mean inclination angle of 44.1 degrees (32.1-56.3); corresponding values for the native acetabulum were 38.9 degrees (20.5-54.8) and 24.8 degrees (4.8-33.6). The residual lower-limb length discrepancy was less than 1mm (mean, -0.04mm [-1.2 to +1.6mm]). The mean angle between the femoral implant and the femoral neck axis was 5.4 degrees of valgus. DISCUSSION: Our results show that HR accurately restored the native extra medullary hip geometry. LEVEL OF EVIDENCE: III, prospective diagnostic case control study. PMID- 26148968 TI - Revealing Three Stages of DNA-Cisplatin Reaction by a Solid-State Nanopore. AB - The dynamic structural behavior in DNA due to interaction with cisplatin is essential for the functionality of platinum-based anti-cancer drugs. Here we report a novel method to monitor the interaction progress in DNA-cisplatin reaction in real time with a solid-state nanopore. The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time. In the first stage, the capture rate decreases rapidly due to DNA discharging as the positive-charged hydrated cisplatin molecules initially bond to the negative-charged DNA and form mono-adducts. In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts. In the third stage, the capture rate decreases again as a result of DNA aggregation. Our study demonstrates a new single-molecule tool in exploring dynamic behaviors during drug-DNA reactions and may have future application in fast drug screening. PMID- 26148969 TI - Human alpha-defensins are immune-related Kv1.3 channel inhibitors: new support for their roles in adaptive immunity. AB - Defensins form a major family of antimicrobial peptides. Recently, human beta defensin 2 and fungal plectasin were shown to be immune-related potassium voltage gated channel subfamily A member 3 (Kv1.3) channel inhibitors. This work continued to show that the human alpha-defensins human neutrophil peptide (HNP) 1 and human defensin (HD) 5 are selective Kv1.3 channel inhibitors with 50% inhibition concentration values of 102.0 +/- 30.3 nM and 2.2 +/- 0.2 MUM, respectively. Furthermore, HNP1 was found to inhibit Kv1.3 currents and IL-2 secretion in human CD3(+) T cells. Despite the structural similarity between HNP1 and HD5, HNP1 could simultaneously bind to the S1-S2 linker and the pore region of the Kv1.3 channel as both a toxinlike blocker and a novel modifier, whereas HD5 could only bind to the channel pore region as a toxinlike blocker. As a channel modifier, HNP1 could shift the conductance-voltage relationship curve of the Kv1.3 channel by ~9.5 mV in the positive direction and could increase the time constant for channel activation through the electrostatic repulsion between the cationic HNP1 anchored in the S1-S2 linker and the positively charged S4 domain of the Kv1.3 channel. Together, these findings reveal that human alpha defensins are novel endogenous inhibitors of Kv1.3 channels with distinct interaction mechanisms, which facilitates future research into their adaptive immune functions. PMID- 26148971 TI - Bone morphogenetic protein signaling promotes morphogenesis of blood vessels, wound epidermis, and actinotrichia during fin regeneration in zebrafish. AB - Zebrafish fin regeneration involves initial formation of the wound epidermis and the blastema, followed by tissue morphogenesis. The mechanisms coordinating differentiation of distinct tissues of the regenerate are poorly understood. Here, we applied pharmacologic and transgenic approaches to address the role of bone morphogenetic protein (BMP) signaling during fin restoration. To map the BMP transcriptional activity, we analyzed the expression of the evolutionarily conserved direct phospho-Smad1 target gene, id1, and its homologs id2a and id3. This analysis revealed the BMP activity in the distal blastema, wound epidermis, osteoblasts, and blood vessels of the regenerate. Blocking the BMP function with a selective chemical inhibitor of BMP type I receptors, DMH1, suppressed id1 and id3 expression and arrested regeneration after blastema formation. We identified several previously uncharacterized functions of BMP during fin regeneration. Specifically, BMP signaling is required for remodeling of plexus into structured blood vessels in the rapidly growing regenerate. It organizes the wound epithelium by triggering wnt5b expression and promoting Collagen XIV-A deposition into the basement membrane. BMP represents the first known signaling that induces actinotrichia formation in the regenerate. Our data reveal a multifaceted role of BMP for coordinated morphogenesis of distinct tissues during regeneration of a complex vertebrate appendage. PMID- 26148970 TI - Lhx6 and Lhx8: cell fate regulators and beyond. AB - As transcription factors of the lines (LIN)-11/Islet (Isl)-1/mitosis entry checkpoint (MEC)-3 (LIM)-homeobox subfamily, LIM homeobox (Lhx)6 and -8 are remarkably conserved and involved in the morphogenesis of multiple organ systems. Lhx6 and -8 play overlapping and distinctive roles, but in general act as cell fate mediators and in turn are regulated by several transcriptional factors, such as sonic hedgehog, fibroblast growth factors, and wingless-int (Wnt)/beta catenin. In this review, we first summarize Lhx6 and -8 distributions in development and then explore how Lhx6 and -8 act as transcription factors and coregulators of cell lineage specification. Known Lhx6 and -8 functions and targets are outlined in neurogenesis, craniofacial development, and germ cell differentiation. The underlying mechanisms of Lhx6 and -8 in regulating cell fate remain elusive. Whether Lhx6 and -8 affect functions in tissues and organs other than neural, craniofacial, oocytes, and germ cells is largely unexplored. Taken together, Lhx6 and -8 are important regulators of cell lineage specification and may act as one of the pivotal mediators of stem cell fate. Undoubtedly, future investigations of Lhx6 and -8 biology will continue to yield fascinating insights into tissue development and homeostasis, in addition to their putative roles in tissue regeneration and ageing. PMID- 26148972 TI - Multiple microRNAs within the 14q32 cluster target the mRNAs of major type 1 diabetes autoantigens IA-2, IA-2beta, and GAD65. AB - Islet antigen (IA)-2, IA-2beta, and glutamate decarboxylase (GAD65) are major autoantigens in type 1 diabetes (T1D). Autoantibodies to these autoantigens appear years before disease onset and are widely used as predictive markers. Little is known, however, about what regulates the expression of these autoantigens. The present experiments were initiated to test the hypothesis that microRNAs (miRNAs) can target and affect the levels of these autoantigens. Bioinformatics was used to identify miRNAs predicted to target the mRNAs coding IA-2, IA-2beta, and GAD65. RNA interference for the miRNA processing enzyme Dicer1 and individual miRNA mimics and inhibitors were used to confirm the effect in mouse islets and MIN6 cells. We show that the imprinted 14q32 miRNA cluster contains 56 miRNAs, 32 of which are predicted to target the mRNAs of T1D autoantigens and 12 of which are glucose-sensitive. Using miRNA mimics and inhibitors, we confirmed that at least 7 of these miRNAs modulate the mRNA levels of the T1D autoantigens. Dicer1 knockdown significantly reduced the mRNA levels of all 3 autoantigens, further confirming the importance of miRNAs in this regulation. We conclude that miRNAs are involved in regulating the expression of the major T1D autoantigens. PMID- 26148974 TI - Continental-scale variation in seaweed host-associated bacterial communities is a function of host condition, not geography. AB - Interactions between hosts and associated microbial communities can fundamentally shape the development and ecology of 'holobionts', from humans to marine habitat forming organisms such as seaweeds. In marine systems, planktonic microbial community structure is mainly driven by geography and related environmental factors, but the large-scale drivers of host-associated microbial communities are largely unknown. Using 16S-rRNA gene sequencing, we characterized 260 seaweed associated bacterial and archaeal communities on the kelp Ecklonia radiata from three biogeographical provinces spanning 10 degrees of latitude and 35 degrees of longitude across the Australian continent. These phylogenetically and taxonomically diverse communities were more strongly and consistently associated with host condition than geographical location or environmental variables, and a 'core' microbial community characteristic of healthy kelps appears to be lost when hosts become stressed. Microbial communities on stressed individuals were more similar to each other among locations than those on healthy hosts. In contrast to biogeographical patterns of planktonic marine microbial communities, host traits emerge as critical determinants of associated microbial community structure of these holobionts, even at a continental scale. PMID- 26148973 TI - Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer specific bioluminescence resonance energy transfer-based sensors. AB - Retinoid X receptors (RXRs) play a role as master regulators because of their capacity to form heterodimers with other nuclear receptors (NRs). Accordingly, retinoid signaling is involved in multiple biologic processes, including development, cell differentiation, metabolism, and cell death. However, the role and function of RXRs in different heterodimer complexes remain unidentified, mainly because most RXR drugs (called rexinoids) are not selective of specific heterodimer complexes. The lack of selectivity strongly limits the use of rexinoids for specific therapeutic approaches. To better characterize rexinoids at specific NR complexes, we have developed and optimized luciferase (Luc) protein complementation(PCA)-based bioluminescence resonance energy transfer (BRET) assays that can directly measure recruitment of a coactivator (CoA) motif fused to yellow fluorescent protein (YFP) by specific NR dimers. To validate the assays, we compared rexinoid modulation of CoA recruitment by the RXR homodimer and by the heterodimers Nur77/RXR and Nurr1/RXR. Results revealed that some rexinoids display selective CoA recruitment activities with homo- or heterodimer complexes. In particular, SR11237 (BMS649) has stronger potency for recruitment of CoA motif and transcriptional activity with the heterodimer Nur77/RXR than other complexes. This technology should be useful in identifying new compounds with specificity for individual dimeric species formed by NRs. PMID- 26148976 TI - Macrophage-derived osteopontin induces reactive astrocyte polarization and promotes re-establishment of the blood brain barrier after ischemic stroke. AB - Infarcted regions of the brain after stroke are segregated from the intact brain by scar tissue comprising both fibrous and glial components. The extent and quality of scarring is influenced by inflammation. The matricellular glycoprotein osteopontin (OPN) is strongly induced in myeloid cells after stroke and may contribute to repair of ischemic brain lesions. To elucidate the role of OPN in scar formation, we induced photothrombotic brain infarction, characterized by circumscribed cortical infarctions with a well-defined border zone toward the intact brain parenchyma. The cellular source and functional role of OPN was addressed by studies in OPN null (OPN(-/-) ) mice, wild-type mice depleted of hematogenous monocytes/macrophages by clodronate-filled liposome treatment, and CCR2(-/-) bone marrow chimeric mice characterized by impaired hematogenous macrophage influx into the infarctions. OPN was mainly produced by hematogenous macrophages infiltrating into the inner border zone of the infarcts whereas astrocyte activation occurred in the outer border zone. In OPN(-/-) as well as macrophage-depleted mice, reactive astrocytes failed to properly extend processes from the periphery toward the center of the infarctions. This was associated with incomplete coverage of neovessels by astrocytic endfeet and persistent leakiness of the damaged blood brain barrier. In conclusion, OPN produced by hematogenous macrophages induces astrocyte process extension toward the infarct border zone, which may contribute to repair of the ischemic neurovascular unit. PMID- 26148975 TI - Excretion of cytoplasmic proteins in Staphylococcus is most likely not due to cell lysis. AB - The excretion of cytoplasmic proteins (ECP) is a long-known phenomenon in bacteria and eukaryotes. So far, it was not possible to associate either a signal peptide-dependent or a signal peptide-independent pathway to ECP. Nevertheless 25% of the proteins found in Staphylococcus aureus supernatants were cytoplasmic proteins. Because the excreted proteins do not possess a common motive, the most widespread opinion is that ECP is due to cell lysis. This explanation seems to be too easy since several indications imply that there exists a yet unknown mechanism for ECP. Certainly, the up-regulation of autolysins as well as decreased peptidoglycan cross-linking increased ECP. However, in recent years, several evidences arose that cell lysis is not the only reason for ECP. It seems that ECP is a part of the normal cell cycle of S. aureus as it turned out that ECP with several model proteins occurs mainly during cell growth. It has common features as proteins secreted via the Sec translocon and finally the excretion site is the cross wall of dividing cells. PMID- 26148977 TI - The Role of Natural Support Systems in the Post-deployment Adjustment of Active Duty Military Personnel. AB - This study examined the relations among three different types of naturally occurring social support (from romantic partners, friends and neighbors, and unit leaders) and three indices of service member well-being (self reports of depressive symptoms, satisfaction with military life, and perceptions of unit readiness) for service members who did and did not report negative experiences associated with military deployment. Data were drawn from the 2011 Community Assessment completed anonymously by more than 63,000 USAF personnel. Regression analyses revealed that higher levels of social support was associated with better outcomes regardless of negative deployment experiences. Evidence of moderation was also noted, with all forms of social support moderating the impact of negative deployment experiences on depressive symptoms and support from unit leaders moderating the impact of negative deployment experience on satisfaction with military life. No moderation was found for perceptions of unit readiness. Subgroup analyses revealed slightly different patterns for male and female service members, with support providing fewer moderation effects for women. These findings may have value for military leaders and mental health professionals working to harness the power of naturally occurring relationships to maximize the positive adjustment of service members and their families. Implications for practices related to re-integration of post-deployment military personnel are discussed. PMID- 26148979 TI - Identifying Perceived Neighborhood Stressors Across Diverse Communities in New York City. AB - There is growing interest in the role of psychosocial stress in health disparities. Identifying which social stressors are most important to community residents is critical for accurately incorporating stressor exposures into health research. Using a community-academic partnered approach, we designed a multi community study across the five boroughs of New York City to characterize resident perceptions of key neighborhood stressors. We conducted 14 community focus groups; two to three in each borough, with one adolescent group and one Spanish-speaking group per borough. We then used systematic content analysis and participant ranking data to describe prominent neighborhood stressors and identify dominant themes. Three inter-related themes regarding the social and structural sources of stressful experiences were most commonly identified across neighborhoods: (1) physical disorder and perceived neglect, (2) harassment by police and perceived safety and (3) gentrification and racial discrimination. Our findings suggest that multiple sources of distress, including social, political, physical and economic factors, should be considered when investigating health effects of community stressor exposures and psychological distress. Community expertise is essential for comprehensively characterizing the range of neighborhood stressors that may be implicated in psychosocial exposure pathways. PMID- 26148978 TI - The Long-Term Economic Benefits of Natural Mentoring Relationships for Youth. AB - Natural mentors have been shown to help improve psychological and educational outcomes of youth, and may serve an important role for youth experiencing risk in the home. Using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we investigated the associations between natural mentors during youth and income during early adulthood, including how these relations were moderated by the absence of a father figure and race. We also estimated the lifetime economic benefits to having a natural mentor. The presence of a natural mentor alone did not have a significant impact on annual earnings during adulthood. However, youth without a father but who had a male mentor earned significantly more, on average, than those without a male mentor. These effects were more pronounced in a subsample of African American youth. The net present value of total lifetime benefits to having a male natural mentor was approximately $190,000 for all fatherless youth and $458,000 for African American fatherless youth. These results suggest that natural mentors play a crucial role in economic outcomes for youth, which may vary by sociodemographic factors. PMID- 26148980 TI - Planning for Sustainability of an Evidence-Based Mental Health Promotion Program in Canadian Elementary Schools. AB - Substantial research illuminates many factors effecting the implementation of evidence-based mental health promotion programs in schools; however, research on how schools plan for sustaining their investments in these programs is limited. In this qualitative study, we elicited descriptions of opportunities and challenges for sustainability. We interviewed 24 individuals from schools involved in a longitudinal, qualitative research project that followed uptake and implementation of the evidence-based WITS Programs across 2 years (Leadbeater et al. 2012). WITS stands for Walk away, Ignore, Talk it out and Seek help and the online WITS Programs focus on preventing peer victimization ( www.witsprograms.ca ). Our findings suggest that sustainability planning in schools is not merely a next step following high quality implementation, but rather involves multiple ongoing processes that need to be anticipated and supported by school leadership and program champions and developers in order to realize investments in evidence based programs. PMID- 26148981 TI - [Urinary protein detection by iTRAQ(r) associated with renal transplant complications and its modification with therapy]. AB - BACKGROUND: After renal transplant, surgical, infection complications, as well as graft rejection may occur; early detection through non-invasive markers is the key to change therapy and avoid biopsy. OBJECTIVE: The aime of the study is to determine urine protein profiles in patients undergoing renal transplant with complications and detect its variation when therapy is modified. MATERIAL AND METHODS: Urine samples were collected from patients prior the transplant and various postoperative stages. Urinary protein profiles were obtained by peptide labeling using isobaric isotopes for relative quantification (iTRAQ((r))). RESULTS: A total of 22 patients were included, of whom 12 developed post transplant complication: 2 with graft rejection (one male and one female) and 10 (6 males and 4 females) in the group of post-transplant infections. Using iTRAQ((r)) 15/345 and 28/113 proteins were identified and fulfilled the acceptance criteria, in graft rejection and post-transplant infections group, respectively. CONCLUSIONS: Albumin was the only protein found in both groups, the remaining proteins were different. The 5 proteins with higher scores in graft rejection were: alpha-1-microglobulin, 5'-nucleotidase cytosolic III, retinol binding protein 4, membrane protein palmitoylated 4, and serine carboxypeptidase, while post-transplant infections were: mitochondrial acetyl-coenzyme A synthetase, putative adenosyl homocysteinase 2, zinc finger protein GLIS1, putative protein FAM157B, and zinc finger protein 615. It remains to elucidate the involvement of each of these in patients with renal transplantation. PMID- 26148982 TI - [Evaluation of 2 inanimate models to improve percutaneous fluoroscopy-guided renal access time]. AB - BACKGROUND: Training devices for percutaneous renal access are expensive, have hazardous biological materials, or radiation. Two devices were designed that eliminate some or all of these characteristics (ManiPERC and iPERC). OBJECTIVE: To compare the improvement in access time to the posterior lower calix with 2 inanimate models in a group of Urology residents. MATERIAL AND METHODS: Quasi experimental clinical trial with 16 Urology residents to compare the improvement over time of percutaneous renal access by training in 2 inanimate models (iPERC: simulated fluoroscopy and ManiPERC: real fluoroscopy). RESULTS: Subjects were assigned to one of 2 groups (iPERC and ManiPERC) and a video analysis of all of them was performed before and after 20 training sessions. Both groups improved their access time; with iPERC from 133.88+/-41.40 to 76+/-12.62s (p=0.006) and from 176.5+/-85.81 to 68.75 to 18.40s (p=0.007) with ManiPERC. Comparing iPERC versus ManiPERC there was no difference between them in improving access time (ANCOVA: Model F (1.13)=1.598, p=0.228). CONCLUSIONS: Both models are equivalent in improving skills; however, even though none of them generated bio-waste, the absence of radioactive emissions makes iPERC the more advantageous model. PMID- 26148983 TI - Joint attention revisited: Finding strengths among children with autism. AB - Differences in joint attention are prominent for some children with autism and are often used as an indicator of the disorder. This study examined the joint attention competencies of young children with autism who demonstrated joint attention ability and compared them to children with developmental delays. A total of 40 children with autism and developmental delays were matched pairwise based on mental and chronological age. Videos of children engaging in play were coded for the frequency and forms (eye contact, gestures, affect, etc.) of joint attention. Additionally, concurrent language was compared among children with autism (N = 32) by their joint attention ability. Children with autism spectrum disorder entered into joint attention significantly less often than children with developmental delays, but once engaged used the forms of joint attention similarly. For the matched pairs, there were no differences in language, but the children with autism who used joint attention had significantly better language than children with autism who did not (even after controlling for mental age). There is a group of young children with autism who can use joint attention but do so at lower frequencies than children with developmental delays. Possible reasons include difficulty disengaging attention and limited intrinsic social motivation to share. Adult persistence is recommended to encourage joint attention. PMID- 26148984 TI - Audiogenic kindling and secondary subcortico-cortical epileptogenesis: Behavioral correlates and electrographic features. AB - Human epilepsy is usually considered to result from cortical pathology, but animal studies show that the cortex may be secondarily involved in epileptogenesis, and cortical seizures may be triggered by extracortical mechanisms. In the audiogenic kindling model, recurrent subcortical (brainstem driven) seizures induce secondary epileptic activation of the cortex. The present review focuses on behavioral and electrographic features of the subcortico cortical epileptogenesis: (1) behavioral expressions of traditional and mild paradigms of audiogenic kindling produced by full-blown (generalized) and minimal (focal) audiogenic seizures, respectively; (2) electrographic manifestations of secondary epileptic activation of the cortex - cortical epileptic discharge and cortical spreading depression; and (3) persistent individual asymmetry of minimal audiogenic seizures and secondary cortical events produced by their repetition. The characteristics of audiogenic kindling suggest that this model represents a unique experimental approach to studying cortical epileptogenesis and network aspects of epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". PMID- 26148985 TI - Which EEG patterns in coma are nonconvulsive status epilepticus? AB - Nonconvulsive status epilepticus (NCSE) is common in patients with coma with a prevalence between 5% and 48%. Patients in deep coma may exhibit epileptiform EEG patterns, such as generalized periodic spikes, and there is an ongoing debate about the relationship of these patterns and NCSE. The purposes of this review are (i) to discuss the various EEG patterns found in coma, its fluctuations, and transitions and (ii) to propose modified criteria for NCSE in coma. Classical coma patterns such as diffuse polymorphic delta activity, spindle coma, alpha/theta coma, low output voltage, or burst suppression do not reflect NCSE. Any ictal patterns with a typical spatiotemporal evolution or epileptiform discharges faster than 2.5 Hz in a comatose patient reflect nonconvulsive seizures or NCSE and should be treated. Generalized periodic diacharges or lateralized periodic discharges (GPDs/LPDs) with a frequency of less than 2.5 Hz or rhythmic discharges (RDs) faster than 0.5 Hz are the borderland of NCSE in coma. In these cases, at least one of the additional criteria is needed to diagnose NCSE (a) subtle clinical ictal phenomena, (b) typical spatiotemporal evolution, or (c) response to antiepileptic drug treatment. There is currently no consensus about how long these patterns must be present to qualify for NCSE, and the distinction from nonconvulsive seizures in patients with critical illness or in comatose patients seems arbitrary. The Salzburg Consensus Criteria for NCSE [1] have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society [2] and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. Their diagnostic utility in different cohorts with patients in deep coma has to be studied in the future. This article is part of a Special Issue entitled "Status Epilepticus". PMID- 26148986 TI - Stress habituation, body shape and cardiovascular mortality. AB - High cardiovascular mortality is well documented in lean phenotypes exhibiting visceral fat accumulation. In contrast, corpulent phenotypes with predominantly subcutaneous fat accumulation display a surprisingly low mortality. The term 'obesity paradox' reflects the difficulty in understanding the biological mechanisms underlying these clinical observations. The allostatic load model of chronic stress focuses on glucocorticoid dysregulation as part of a 'network of allostasis' involving autonomic, endocrine, metabolic, and immune mediators. Here, we expand upon the energetic demands of the brain and show that 'habituators' and 'non-habituators' develop divergent patterns of fat distribution. Central to this process is the recurrent rise in the cerebral energy need (arousal) that non-habituators experience during chronic stress. These neuroenergetic alterations promote visceral fat accumulation, subcutaneous fat loss, and atherogenesis with subsequent cardiovascular events. Habituators are more or less protected against such cardiovascular complications, but there is a metabolic trade-off that we shall discuss in the present paper. PMID- 26148987 TI - Meta-analysis of female stress urinary incontinence treatments with adjustable single-incision mini-slings and transobturator tension-free vaginal tape surgeries. AB - BACKGROUND: The study on SIMS and SMUS as a whole by Alyaa Mostafa et al showed that after excluding the TVT-S sling, there is no significant difference in patient-reported cure rate and objective cure rate between these two methods. In this paper, we systematically evaluate the relevant data on SIMS-Ajust and TVT O/TOT and further confirm their safety and effectiveness, providing reliable clinical evidence. METHODS: By searching the Medline, Embase, Scopus, and Web of Science databases and the Cochrane Database of Systematic Reviews combined with manual searches, all reports on randomized controlled trials (RCTs) of single incision mini-sling (SIMS-Ajust) and transobturator tension-free vaginal tape (TVT-O/TOT) surgeries were collected. Using RevMan 5.2 statistical software, the patient-reported cure rate, objective cure rate, operative time, postoperative pain, lower urinary tract injuries, groin pain, postoperative voiding difficulties, de novo urgency and/or worsening of preexisting surgery, vaginal tape erosion, repeated continence surgery, and other related data on both surgical methods were evaluated. RESULTS: A total of 154 relevant research reports were retrieved, and five randomized controlled trials were included in this study, involving a total of 678 patients. The meta-analysis results show no significant difference in the patient-reported cure rate and objective cure rate between SIMS-Ajust and TVT-O/TOT [RR = 0.95, 95% CI (0.87 to 1.04), P > 0.05; RR = 0.97, 95% CI (0.90-1.05), P > 0.05]. With respect to operation time and groin pain, SIMS-Ajust outperforms TVT-O/TOT [MD = -1.61, 95% CI (-2.48 to 0.74), P < 0.05; RR = 0.30, 95% CI (0.11 to 0.85), P < 0.05]. In terms of postoperative pain, lower urinary tract injuries, postoperative voiding difficulties, de novo urgency and/or worsening of preexisting surgery, vaginal tape erosion, and repetition of continence surgery, there is no significant difference between SIMS Ajust and TVT-O/TOT [RR = 0.50, 95% CI(0.18-1.43), P > 0.05; RR = 2.82, 95% CI(0.14-57.76), P > 0.05; RR = 0.64, 95% CI(0.28-1.45), P > 0.05; RR = 1.06, 95% CI(0.66-1.71), P > 0.05; RR = 1.04, 95% CI(0.24-4.45), P > 0.05; RR = 1.64, 95% CI(0.41-6.61), P > 0.05]. CONCLUSIONS: SIMS-Ajust is safe and effective in the treatment of female stress urinary incontinence. Compared with TVT-O/TOT surgery, SIMS-Ajust surgery has the same high objective cure rate and patient-reported cure rate and low incidence of perioperative complications, in addition to its short operative time and low incidence of groin pain. Its long-term efficacy needs further observation. PMID- 26148988 TI - Matching Chelators to Radiometals for Positron Emission Tomography Imaging- Guided Targeted Drug Delivery. AB - Positron emission tomography (PET) is a functional imaging modality that measures pathophysiology status of disease noninvasively, and has become a key component for innovative drug delivery system (DDS) studies recently. The development of multifunctional chelating agents is critical for developing PET radiopharmaceuticals and therefore has become a hot and demanding research topic recently. The optimal chelators should be readily attached to biomolecules covalently, able to form stable complexes with radiometals, and demonstrate good bio-distribution pattern in vivo. Indeed, the selection of suitable chelators can facilitate the development of an effective PET imaging probe by improving targeting properties and providing favorable in vivo pharmacokinetics of radiolabeled probes. This review focuses on the recent developments of multifunctional chelators that are suitable for both imaging and radiation therapy. PMID- 26148990 TI - A mutation in the Gardos channel is associated with hereditary xerocytosis. AB - The Gardos channel is a Ca(2+)-sensitive, intermediate conductance, potassium selective channel expressed in several tissues including erythrocytes and pancreas. In normal erythrocytes, it is involved in cell volume modification. Here, we report the identification of a dominantly inherited mutation in the Gardos channel in 2 unrelated families and its association with chronic hemolysis and dehydrated cells, also referred to as hereditary xerocytosis (HX). The affected individuals present chronic anemia that varies in severity. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. The missense mutation concerns a highly conserved residue among species, located in the region interacting with Calmodulin and responsible for the channel opening and the K(+) efflux. Using 2-microelectrode experiments on Xenopus oocytes and patch-clamp electrophysiology on HEK293 cells, we demonstrated that the mutated channel exhibits a higher activity and a higher Ca(2+) sensitivity compared with the wild type (WT) channel. The mutated channel remains sensitive to inhibition suggesting that treatment of this type of HX by a specific inhibitor of the Gardos channel could be considered. The identification of a KCNN4 mutation associated with chronic hemolysis constitutes the first report of a human disease caused by a defect of the Gardos channel. PMID- 26148991 TI - Automatic process control in anaerobic digestion technology: A critical review. AB - Anaerobic digestion (AD) is a mature technology that relies upon a synergistic effort of a diverse group of microbial communities for metabolizing diverse organic substrates. However, AD is highly sensitive to process disturbances, and thus it is advantageous to use online monitoring and process control techniques to efficiently operate AD process. A range of electrochemical, chromatographic and spectroscopic devices can be deployed for on-line monitoring and control of the AD process. While complexity of the control strategy ranges from a feedback control to advanced control systems, there are some debates on implementation of advanced instrumentations or advanced control strategies. Centralized AD plants could be the answer for the applications of progressive automatic control field. This article provides a critical overview of the available automatic control technologies that can be implemented in AD processes at different scales. PMID- 26148989 TI - Opportunities for Photoacoustic-Guided Drug Delivery. AB - Photoacoustic imaging (PAI) is rapidly becoming established as a viable imaging modality for small animal research, with promise of near-future human clinical translation. In this review, we discuss emerging prospects for photoacoustic guided drug delivery. PAI presents opportunities for applications related to drug delivery, mainly with respect to either monitoring drug effects or monitoring drugs themselves. PAI is well-suited for imaging disease pathology and treatment response. Alternatively, PAI can be used to directly monitor the accumulation of various light-absorbing contrast agents or carriers with theranostic properties. PMID- 26148993 TI - Analysis of interval-censored recurrent event processes subject to resolution. AB - Interval-censored recurrent event data arise when the event of interest is not readily observed but the cumulative event count can be recorded at periodic assessment times. In some settings, chronic disease processes may resolve, and individuals will cease to be at risk of events at the time of disease resolution. We develop an expectation-maximization algorithm for fitting a dynamic mover stayer model to interval-censored recurrent event data under a Markov model with a piecewise-constant baseline rate function given a latent process. The model is motivated by settings in which the event times and the resolution time of the disease process are unobserved. The likelihood and algorithm are shown to yield estimators with small empirical bias in simulation studies. Data are analyzed on the cumulative number of damaged joints in patients with psoriatic arthritis where individuals experience disease remission. PMID- 26148992 TI - Similar activation state of neutrophils in sputum of asthma patients irrespective of sputum eosinophilia. AB - Inflammatory phenotypes of asthma are associated with differences in disease characteristics. It is unknown whether these inflammatory phenotypes are reflected by the activation status of neutrophils in blood and sputum. We obtained peripheral blood and induced sputum from 21 asthma patients and stratified our samples based on sputum eosinophilia resulting in two groups (>3% eosinophils: n = 13, <3%: n = 8). Eosinophils and neutrophils from blood and sputum were analysed for expression of activation and degranulation markers by flow cytometry. Data were analysed by both classical, non-parametric statistics and a multi-dimensional approach, using principal component analysis (PCA). Patients with sputum eosinophilia were characterized by increased asthma control questionnaire (ACQ) scores and blood eosinophil counts. Both sputum neutrophils and eosinophils displayed an activated and degranulated phenotype compared to cells obtained from blood. Specifically, degranulation of all granule types was detected in sputum cells, combined with an increased expression of the activation markers (activated) Mac-1 (CD11b), programmed death ligand 1 (PD-L1) (CD274) and a decreased expression of CD62L. CD69 expression was only increased on sputum eosinophils. Surface marker expression of neutrophils was similar in the presence or absence of eosinophilia, either by single or multi-dimensional analysis. Sputum neutrophils were highly activated and degranulated irrespective of sputum eosinophilia. Therefore, we conclude that differences in granulocyte activation in sputum and/or blood are not associated with clinical differences in the two groups of asthma patients. The finding of PD-L1 expression on sputum granulocytes suggests an immunomodulatory role of these cells in the tissue. PMID- 26148994 TI - Relationship between Ulcerative Colitis and Lung Injuries. AB - OBJECTIVE: To explore the relationship between ulcerative colitis (UC) and lung injuries by assessing their clinical manifestations and characteristics. METHODS: From July 2009 to April 2012, 91 UC patients presenting to Longhua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study. According to the scores of disease activity index, the patients were divided into the mild, moderate, and severe groups. Meanwhile, the records of pulmonary symptoms, chest X-ray image, and pulmonary function were reviewed. RESULTS: Sixty-eight (74.7%) patients had at least 1 pulmonary symptom, such as cough (38.5%), shortness of breath (27.5%), and expectoration (17.6%). And 77 (84.6%) had at least 1 ventilation abnormality. Vital capacity value was significantly lower in the severe group than that in the mild group (91.82%+/ 10.38% vs. 98.92%+/-12.12%, P<0.05). CONCLUSIONS: Lung injury is a common extraintestinal complication of UC. According to the theory in Traditional Chinese Medicine that the lung and large intestine are related, both the lungs and large intestine should be treated simultaneously. PMID- 26148995 TI - Evaluation of Tubal Patency with Transvaginal Three-dimensional Hysterosalpingo contrast Sonography. AB - OBJECTIVE: To investigate diagnostic efficacy of transvaginal three-dimensional hysterosalpingo-contrast sonography (3D-HyCoSy) in assessing tubal patency with chromolaporoscopy. METHODS: A total of 157 infertile women underwent 3D-HyCoSy to evaluate tubal patency. Among these patients, 39 patients were also examined by chromolaporoscopy. The concordance of the two clinical assessment methods was analyzed by the Kappa coefficient test. RESULTS: Among the 306 oviducts examined by 3D-HyCoSy, 99 (32.4%) were patent, 126 (41.2%) partially obstructed, and 81 (26.5%) completely obstructed. Diagnostic results with 3D-HyCoSy were not statistically different from those obtained in the 39 women (78 oviducts) who also underwent chromolaporoscopy, and the two methods showed a high concordance (k=0.747, P=0.000). The 3D-HyCoSy procedure had a sensitivity of 84.8% (28/33), a specificity of 96.2% (25/26), and positive and negative predictive values of 93.3% (28/30) and 86.2% (25/29) respectively. CONCLUSION: Transvaginal 3D-HyCoSy can accurately reveal the spatial path and morphology of the oviduct and is a safe and effective method to evaluate tubal patency. PMID- 26148996 TI - Perinipple Broken Line Incision: a Novel Approach for Breast Augmentation. AB - OBJECTIVE: To investigate reliability of the infra-nipple broken line incision for breast augmentation. METHODS: From January 2012 to January 2013, 15 patients underwent primary bilateral retromuscular breast augmentation with round textured silicone-gel implants and a novel infra-nipple broken line incision. Preoperatively, a semicircular incision was marked along the inferior base of the nipple. It was then extended bilaterally using two transverse right-angled geometric broken lines within the pigmented areolar skin. Follow-up was performed to evaluate the sensation of nipple-areolar complex, the scar, and the shape and texture of the breasts. RESULTS: The average follow-up was 6.7 months. Most of the patients complained of paresthesia of the nipple or breast skin, but transient decreased sensation improved within 3 months. No patients showed permanent sensory changes of the nipple areolar complex at a minimum follow-up of 4 months. The scars were imperceptible in all patients. CONCLUSION: We believe that for selected patients, the infra-nipple broken line incision is a practical and reliable method to achieve aesthetic result. PMID- 26148997 TI - Impact of Laparoscopic Versus Open Hepatectomy on Perioperative Clinical Outcomes of Patients with Primary Hepatic Carcinoma. AB - OBJECTIVE: To compare the perioperative outcomes of patients with primary hepatic carcinoma treated with laparoscopic hepatectomy (LH) with those treated with open hepatectomy (OH). METHODS: From January 2010 to August 2014, 100 patients with primary hepatic carcinoma were randomly divided into the LH group and OH group respectively, 50 patients in each group. And the incision length, blood loss, operative time, postoperative liver function, anus exhaust time, complications, length of postoperative hospital stay, and cost measures were compared. RESULTS: LH could achieve shorter incision length, less blood loss, more rapid recovery in liver function and gastrointestinal function, and shorter postoperative hospital stay length compared with OH for primary hepatic carcinoma patients (all P<0.05). However, LH could not significantly shorten operative time, and reduce postoperative complications and hospitalization cost (all P>0.05). CONCLUSION: Compared with OH, LH could improve perioperative outcomes of primary hepatic carcinoma patients. PMID- 26148998 TI - Effect of Neoadjuvant Chemotherapy Treatment on Prognosis of Patients with Advanced Gastric Cancer: a Retrospective Study. AB - OBJECTIVE: To evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer. METHODS: We retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups. RESULTS: According to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025). CONCLUSION: In patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications. PMID- 26148999 TI - Clinical Characteristics and Outcome of Gleason Score 10 Prostate Cancer on Core Biopsy Treated by External Radiotherapy and Hormone Therapy. AB - OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with Gleason score 10 prostate cancer treated by external radiotherapy and hormone therapy. METHODS: From January 2003 to March 2014, 1832 patients with prostate cancer were treated, among which 9 patients (represented 0.49%) were identified as Gleason score 10 disease on prostate core biopsy without distant metastases when first diagnosed. All 9 patients were treated by whole pelvic external radiotherapy (The whole pelvic dose was 50.0 Gy and the boost dose ranged from 76.2 to 78.0 Gy) and long-term hormone therapy. We assessed the clinical characteristics, treatment outcomes and treatment toxicities. Survival curves were calculated using the Kaplan-Meier method. RESULTS: The median follow-up was 4.8 years. Six patients' pre-treatment prostate-specific antigen (PSA) levels were lower than 20.0 MUg/L and three patients' pre-treatment PSA levels were higher than 70.0 MUg/L. The median percentage of positive biopsy cores was 91%. Three, four and two cases were classified as T2c, T3a and T3b stage, respectively. Three cases were assessed as N1 stage. The 5-year biochemical failure-free survival, distant metastasis-free survival, cancer specific survival and overall survival rates were 28.6%, 57.1%, 66.7% and 57.1%, respectively. Five patients experienced grade 1-2 acute gastrointestinal toxicities and six patients complained of grade 1-2 acute genitourinary toxicities. No bone fracture or cardiovascular disease was detected. CONCLUSIONS: Gleason score 10 prostate cancer on core biopsy is usually combined with other high risk factors. The pre treatment PSA levels lie in two extremes. Timely and active treatments are urgent needed because unfavourable oncological outcomes are often presented. PMID- 26149000 TI - Assessment of Stroke Volume Variation Perioperatively by Using Arterial Pressure with Cardiac Output. AB - OBJECTIVE: To observe the sensitivity of stroke volume variation (SVV) for assessing volume change during induction period of general anesthesia. METHODS: Patients who underwent orthopaedic surgery under general anesthesia and mechanical ventilation were divided into two groups randomly. Patients in the group Iwere subjected to progressive central hypovolemia and correction of hypovolemia sequentially; patients in the Group II were exposed to hypervolemia alone. Each step was implemented after 5 minutes when the hemodynamics was stable. SVV and cardiac index (CI) were recorded, and Pearson's product-moment correlation was used to analyze correlation between SVV and CI. RESULTS: Forty patients were included in this study, 20 cases in each group. For group I patients, SVV was increased significantly along with blood volume reduction, and changes in CI were negatively correlated with changes in SVV (r=-0.605, P<0.01); SVV decreased significantly along with correction of blood volume; changes in CI were negatively correlated with changes in SVV (r=-0.651, P<0.01). For group II patients, along with blood volume increase, SVV did not change significantly; changes in CI revealed no significant correlation with changes in SVV (r=0.067, P>0.05). CONCLUSION: SVV is a useful indicator for hypovolemia, but not for hypervolemia. PMID- 26149001 TI - Propofol can Protect Against the Impairment of Learning-memory Induced by Electroconvulsive Shock via Tau Protein Hyperphosphorylation in Depressed Rats. AB - OBJECTIVE: To explore the possible neurophysiologic mechanisms of propofol and N methyl-D- aspartate (NMDA) receptor antagonist against learning-memory impairment of depressed rats without olfactory bulbs. METHODS: Models of depressed rats without olfactory bulbs were established. For the factorial design in analysis of variance, two intervention factors were included: electroconvulsive shock groups (with and without a course of electroconvulsive shock) and drug intervention groups [intraperotoneal (ip) injection of saline, NMDA receptor antagonist MK-801 and propofol. A total of 60 adult depressed rats without olfactory bulbs were randomly divided into 6 experimental groups (n=10 per group): ip injection of 5 ml saline; ip injection of 5 ml of 10 mg/kg MK-801; ip injection of 5 ml of 10 mg/kg MK-801 and a course of electroconvulsive shock; ip injection of 5 ml of 200 mg/kg propofol; ip injection of 5 ml of 200 mg/kg propofol and a course of electroconvulsive shock; and ip injection of 5 ml saline and a course of electroconvulsive shock. The learning-memory abilities of the rats was evaluated by the Morris water maze test. The content of glutamic acid in the hippocampus was detected by high-performance liquid chromatography. The expressions of p AT8Ser202 in the hippocampus were determined by Western blot analysis. RESULTS: Propofol, MK-801 or electroconvulsive shock alone induced learning-memory impairment in depressed rats, as proven by extended evasive latency time and shortened space probe time. Glutamic acid content in the hippocampus of depressed rats was significantly up-regulated by electroconvulsive shock and down-regulated by propofol, but MK-801 had no significant effect on glutamic acid content. Levels of phosphorylated Tau protein p-AT8Ser202 in the hippocampus was up regulated by electroconvulsive shock but was reduced by propofol and MK-801 alone. Propofol prevented learning-memory impairment and reduced glutamic acid content and p-AT8Ser202 levels induced by electroconvulsive shock. CONCLUSION: Electroconvulsive shock might reduce learning-memory impairment caused by protein Tau hyperphosphorylation in depressed rats by down-regulating glutamate content. PMID- 26149002 TI - Dynamic Expression Profiles of Marker Genes in Osteogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells. AB - OBJECTIVE: To observe the expression profiles of osteoblast-related genes in human mesenchymal stem cells (MSCs) derived from bone marrow during osteogenic differentiation. METHODS: MSCs were induced to differentiate with MSC osteogenic differentiation medium for 7, 14, 21 and 28 days respectively. Alizarin Red staining was used to detect matrix mineralization. Expression of osteoblast related genes, including osteocalcin, osteopontin, Runt-related transcription factor 2 (Runx2), alkaline phosphatase and collagen type 1, was assessed with quantitative reverse transcription-polymerase chain reaction. RESULTS: On day 14 after induction of differentiation, cells were stained positively with Alizarin Red. The expression levels of these genes exhibited an upward trend as induction time was prolonged. Exposure to osteogenic differentiation medium less than 21 days did not significantly induce osteocalcin expression; osteocalcin expression levels in the differentiated cells induced for 21 and 28 days were 1.63 and 2.46 times as high as the undifferentiated cells respectively (all P<0.05). Stimulation with MSC osteogenic differentiation medium over 14 days significantly enhanced bone marrow-derived MSCs to express osteopontin and Runx2 genes (all P<0.05). Osteogenic differentiation medium could significantly induce the expressions of alkaline phosphatase and collagen type1 genes (all P<0.05). Their expressions reached the peak levels on day 21, which were increased more than 4- and 3-fold respectively. CONCLUSION: Human bone marrow-derived MSCs could exhibit the sequential expression pattern of osteoblast marker genes during osteogenic differentiation in vitro. PMID- 26149003 TI - Impact of 1, 25-(OH)2D3 on Left Ventricular Hypertrophy in Type 2 Diabetic Rats. AB - OBJECTIVE: To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy (LVH) in type 2 diabetic rats. METHODS: Type 2 diabetic mellitus (DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy (LVH) by ultrasound examination, and randomly assigned into three groups: untreated (DM-LVH, n=7), treated with insulin (DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3 (DM-LVH+VD, n=6). Healthy male rats were used as the controls group (n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later. RESULTS: In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group (P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased (all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group (P<0.05), whereas the other parameters were significantly decreased (all P<0.05). CONCLUSION: 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression. PMID- 26149004 TI - Confounding Effect in Clinical Research of Otolaryngology and Its Control. AB - Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect. PMID- 26149005 TI - Postoperative Early Standard and Sequential Nutritional Support in the Treatment of Gastroesophageal Anastomotic Fistula: a Case Report. PMID- 26149006 TI - Correction: Study of the one-photon and two-photon properties of two water soluble terpyridines and their zinc complexes. AB - Correction for 'Study of the one-photon and two-photon properties of two water soluble terpyridines and their zinc complexes' by Pengfei Shi et al., Dalton Trans., 2015, 44, 8041-8048. PMID- 26149007 TI - The effect of changing plantarflexion resistive moment of an articulated ankle foot orthosis on ankle and knee joint angles and moments while walking in patients post stroke. AB - BACKGROUND: The adjustment of plantarflexion resistive moment of an articulated ankle-foot orthosis is considered important in patients post stroke, but the evidence is still limited. Therefore, the aim of this study was to investigate the effect of changing the plantarflexion resistive moment of an articulated ankle-foot orthosis on ankle and knee joint angles and moments in patients post stroke. METHODS: Gait analysis was performed on 10 subjects post stroke under four different plantarflexion resistive moment conditions using a newly designed articulated ankle-foot orthosis. Data were recorded using a Bertec split-belt instrumented treadmill in a 3-dimensional motion analysis laboratory. FINDINGS: The ankle and knee sagittal joint angles and moments were significantly affected by the amount of plantarflexion resistive moment of the ankle-foot orthosis. Increasing the plantarflexion resistive moment of the ankle-foot orthosis induced significant decreases both in the peak ankle plantarflexion angle (P<0.01) and the peak knee extension angle (P<0.05). Also, the increase induced significant increases in the internal dorsiflexion moment of the ankle joint (P<0.01) and significantly decreased the internal flexion moment of the knee joint (P<0.01). INTERPRETATION: These results suggest an important link between the kinematic/kinetic parameters of the lower-limb joints and the plantarflexion resistive moment of an articulated ankle-foot orthosis. A future study should be performed to clarify their relationship further so that the practitioners may be able to use these parameters as objective data to determine an optimal plantarflexion resistive moment of an articulated ankle-foot orthosis for improved orthotic care in individual patients. PMID- 26149009 TI - Journal of Thrombosis and Haemostasis. Special Issue: State of the Art 2015. Preface. PMID- 26149008 TI - Low femoral antetorsion as a risk factor for bony impingement after bipolar hemiarthroplasty. AB - INTRODUCTION: Reports of dislocation after bipolar hemiarthroplasty (BHA) abound in literature, and several studies have mentioned the factors that are associated with an increased risk of dislocation. However, there is no report detailing the pattern of impingement in BHA and how femoral antetorsion can affect the range of motion (ROM) after BHA. PURPOSE: The purpose of this study was to evaluate the pattern of impingement in BHA and whether femoral antetorsion affects the ROM after BHA using three-dimensional (3D) dynamic motion analysis. METHODS: Using the computed tomography (CT) data of 60 patients (60 hips), including 31 men and 29 women who underwent BHA for the treatment of idiopathic osteonecrosis (ION) of the femoral head, we calculated the antetorsion of the femoral neck, ROM of flexion (Flex), internal rotation (Int-R), and external rotation (Ext-R) using a CT-based 3D simulation software. We evaluated the pattern of impingement and the relationship between femoral antetorsion and ROM in BHA. As for the implant position in the 3D simulation software, the anteversion of the femoral implant was set to be the same as the natural antetorsion of the femoral neck and neck length was set to be the standard neck in all cases. RESULTS: This study revealed the mechanism of impingement in BHA: (1) bone to bone impingement and (2) implant to bone impingement. We found a significant decrease in the ROM of Flex and Int-R inversely proportional to the femoral antetorsion. In patients with lower femoral antetorsion, the ROM of Flex and Int-R decreased due to bony impingement (the anterior great trochanteric region of the femur impinges on the anteroinferior edge of the anteroinferior iliac spine). Whereas, high anteversion of the femoral implant may decrease the ROM of Ext-R; however, our results also showed that even the lowest ROM of Ext-R with 10 degrees hip extension was over 40 degrees . CONCLUSIONS: We demonstrated that lower femoral antetorsion substantially affects the ROM of Flex and Int-R due to bony impingement. For these patients, there should be consideration given to retaining femoral "anterior offset" in BHA. PMID- 26149010 TI - P2Y12 receptors: structure and function. AB - The platelet P2Y12 receptor (P2Y12R) for adenosine 5'diphosphate (ADP) plays a central role in platelet function, hemostasis, and thrombosis. Patients with inherited P2Y12R defects display mild-to-moderate bleeding diatheses. Defects of P2Y12R should be suspected when ADP, even at high concentrations (>= 10 MUm), is unable to induce full, irreversible platelet aggregation. P2Y12R also plays a role in inflammation: its role in the pathogenesis of allergic asthma has been well characterized. In addition, inhibition or genetic deficiency of P2Y12R has antitumor effects. Drugs inhibiting P2Y12R are potent antithrombotic drugs. Clopidogrel is the P2Y12R antagonist that is most widely used in the clinical setting. Its most important drawback is its inability to inhibit adequately P2Y12R-dependent platelet function in about one-third of patients. New drugs, such as prasugrel and ticagrelor, which effectively inhibit P2Y12R in the vast majority of patients, have proved to be more efficacious than clopdidogrel in preventing major adverse cardiovascular events. PMID- 26149012 TI - Fibrinolytic and procoagulant activities of Yersinia pestis and Salmonella enterica. AB - Pla of the plague bacterium Yersinia pestis and PgtE of the enteropathogen Salmonella enterica are surface-exposed, transmembrane beta-barrel proteases of the omptin family that exhibit a complex array of interactions with the hemostatic systems in vitro, and both proteases are established virulence factors. Pla favors fibrinolysis by direct activation of plasminogen, inactivation of the serpins plasminogen activator inhibitor-1 and alpha2 antiplasmin, inactivation of the thrombin-activable fibrinolysis inhibitor, and activation of single-chain urokinase. PgtE is structurally very similar but exhibits partially different functions and differ in expression control. PgtE proteolysis targets control aspects of fibrinolysis, and mimicry of matrix metalloproteinases enhances cell migration that should favor the intracellular spread of the bacterium. Enzymatic activity of both proteases is strongly influenced by the environment-induced variations in lipopolysaccharide that binds to the beta-barrel. Both proteases cleave the tissue factor pathway inhibitor and thus also express procoagulant activity. PMID- 26149011 TI - Pathogen activators of plasminogen. AB - Group A streptococci (GAS) express soluble and surface-bound virulence factors. Secreted streptokinase (SK) allelic variants exhibit varying abilities to activate host plasminogen (Pg), and GAS pathogenicity is associated with Pg activation and localization of the resulting plasmin (Pm) on the bacterial surface to promote dissemination. The various mechanisms by which GAS usurp the host proteolytic system are discussed, including the molecular sexuality mechanism of conformational activation of the Pg zymogen (Pg*) and subsequent proteolytic activation of substrate Pg by the S*KPg* and SK*Pm catalytic complexes. Substantial progress has been made to delineate both processes in a unified mechanism. Pm coats the bacteria by direct and indirect binding pathways involving plasminogen-binding group A streptococcal M-like (PAM) protein and host fibrin(ogen). Transgenic mouse models using human Pg are being optimized to mimic infections by SK variants in humans and to define in vivo combined mechanisms of these variants and PAM. PMID- 26149013 TI - Reincarnation of ancient links between coagulation and complement. AB - Throughout evolution, organisms have developed means to contain wounds by simultaneously limiting bleeding and eliminating pathogens and damaged host cells via the recruitment of innate defense mechanisms. Disease emerges when there is unchecked activation of innate immune and/or coagulation responses. A key component of innate immunity is the complement system. Concurrent excess activation of coagulation and complement - two major blood-borne proteolytic pathways - is evident in numerous diseases, including atherosclerosis, diabetes, venous thromboembolic disease, thrombotic microangiopathies, arthritis, cancer, and infectious diseases. Delineating the cross-talk between these two cascades will uncover novel therapeutic insights. PMID- 26149014 TI - New approaches to gene and cell therapy for hemophilia. AB - Hemophilia is considered suitable for gene therapy because it is caused by a single gene abnormality, and therapeutic coagulation factor levels may vary across a broad range. Recent success of hemophilia B gene therapy with an adeno associated virus (AAV) vector in a clinical trial showed the real prospect that, through gene therapy, a cure for hemophilia may become a reality. However, AAV mediated gene therapy is not applicable to patients with hemophilia A at present, and neutralizing antibodies against AAV reduce the efficacy of AAV-mediated strategies. Because patients that benefit from AAV treatment (hemophilia B without neutralizing antibodies) are estimated to represent only 15% of total patients with hemophilia, the development of basic technologies for hemophilia A and those that result in higher therapeutic effects are critical. In this review, we present an outline of gene therapy methods for hemophilia, including the transition of technical developments thus far and our novel techniques. PMID- 26149015 TI - Platelet-delivered therapeutics. AB - We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within alpha-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches. PMID- 26149017 TI - Mesenchymal stem cell treatment for hemophilia: a review of current knowledge. AB - Hemophilia remains a non-curative disease, and patients are constrained to undergo repeated injections of clotting factors. In contrast, the sustained production of endogenous factors VIII (FVIII) or IX (FIX) by the patient's own cells could represent a curative treatment. Gene therapy has thus provided new hope for these patients. However, the issues surrounding the durability of expression and immune responses against gene transfer vectors remain. Cell therapy, involving stem cells expanded in vitro, can provide de novo protein synthesis and, if implanted successfully, could induce a steady-state production of low quantities of factors, which may keep the patient above the level required to prevent spontaneous bleeding. Liver-derived stem cells are already being assessed in clinical trials for inborn errors of metabolism and, in view of their capacity to produce FVIII and FIX in cell culture, they are now also being considered for clinical application in hemophilia patients. PMID- 26149016 TI - Gene therapy in an era of emerging treatment options for hemophilia B. AB - Factor IX deficiency (hemophilia B) is less common than factor VIII deficiency (hemophilia A), and innovations in therapy for hemophilia B have generally lagged behind those for hemophilia A. Recently, the first sustained correction of the hemophilia bleeding phenotype by clotting factor gene therapy has been described using recombinant adeno-associated virus (AAV) to deliver factor IX. Despite this success, many individuals with hemophilia B, including children, men with active hepatitis, and individuals who have pre-existing natural immunity to AAV, are not eligible for the current iteration of hemophilia B gene therapy. In addition, recent advances in recombinant factor IX protein engineering have led some hemophilia treaters to reconsider the urgency of genetic cure. Current clinical and preclinical approaches to advancing AAV-based and alternative approaches to factor IX gene therapy are considered in the context of current demographics and treatment of the hemophilia B population. PMID- 26149018 TI - Longer-acting clotting factor concentrates for hemophilia. AB - Hemophilia, when severe, leads to spontaneous life-threatening bleeding episodes. Current therapy requires frequent intravenous infusions. Most patients must limit their physical activities to avoid bleeding when the factor activity levels are below normal. In 2014, new therapeutic factor VIII and IX products were approved in Canada and the U.S. Over the next couple of years, other new factor products will likely be approved. These new factors have been engineered to have improved pharmacokinetic properties, including extended half-life in circulation, thus providing major therapeutic advances for patients with hemophilia. In the completed clinical trials, over 700 patients have successfully used these longer acting products regularly for more than one year. These promising new therapies should allow patients with hemophilia to use fewer infusions to prevent spontaneous bleeding or to treat bleeding episodes, and to provide appropriate clotting factor levels for different physical activities. PMID- 26149020 TI - Half-life extended factor VIII for the treatment of hemophilia A. AB - Prophylactic infusion of factor VIII (FVIII) prevents joint bleeding and other hemorrhages in patients with hemophilia A. Conventional FVIII concentrates have a short half-life, with an average of about 12 h in adults, ranging in individual patients between 6 and 24 h, and even shorter in younger children. Therefore, effective prophylaxis requires frequent intravenous injection, usually three times per week or every other day. Several technologies are currently under investigation to extend the half-life of FVIII, including Fc fusion (Eloctate, Elocta, efmoroctocog alfa), addition of polyethylene glycol (turoctocog alfa pegol [N8-GP], BAY 94-9027, BAX 855), and a single-chain construct (CSL627). This review summarizes characteristics of products in clinical development and discusses their potential benefits. PMID- 26149019 TI - alphaIIbbeta3: structure and function. AB - During the past decade, advanced techniques in structural biology have provided atomic level information on the platelet integrin alphaIIbbeta3 activation mechanism that results in it adopting a high-affinity ligand-binding conformation(s). This review focuses on advances in imaging intact alphaIIbbeta3 in a lipid bilayer in the absence of detergent and new structural insights into the changes in the ligand-binding pocket with receptor activation and ligand binding. It concludes with descriptions of novel therapeutic alphaIIbbeta3 antagonists being developed based on an advanced knowledge of the receptor's structure. PMID- 26149021 TI - New strategies for effective treatment of vitamin K antagonist-associated bleeding. AB - Vitamin K antagonists have been used as oral anticoagulants in the treatment and prevention of thromboembolic events for over half a century. Although vitamin K antagonists are effective in the management of thromboembolic events, the need for routine monitoring and the associated risk of bleeding has resulted in the development and licensing of direct oral anticoagulants for specific clinical indications. Despite these developments, vitamin K antagonists remain the oral anticoagulants of choice in many clinical conditions. Severe bleeding associated with oral anticoagulation requires urgent reversal. Several options for the reversal of vitamin K antagonist exist, including vitamin K, prothrombin complex concentrates and plasma. In this manuscript, we review current evidence and provide physicians with treatment strategies for more effective management of vitamin K antagonist-associated bleeding. PMID- 26149022 TI - Reversal of oral factor Xa inhibitors by prothrombin complex concentrates: a re appraisal. AB - Oral factor Xa inhibitors are an attractive class of anticoagulants expected to have broad application. Rapid and reliable reversal of the anticoagulant effect is important for patients with bleeding complications or those in need of urgent reversal for procedures. While no specific reversal agent is yet available, multiple published clinical guidelines suggest that four-factor prothrombin complex concentrates (PCC) should be considered when urgent reversal is desired. This presentation updates prior reviews on this topic (Crit Care, 17, 2013, 230; Thromb Haemost, 111, 2014, 189; J Thromb Thrombolysis, 2015, 39, 395); and summarizes more recent evidence in human studies indicating that four-factor PCCs available in North America do not reverse oral factor Xa-inhibitor anticoagulants. New agents on the horizon appear to be far more promising as therapies for reversal or oral factor Xa inhibitors. PMID- 26149023 TI - Tranexamic acid in trauma: how should we use it? AB - Tranexamic acid (TXA) reduces blood loss by inhibiting the enzymatic breakdown of fibrin. It is often used in surgery to decrease bleeding and the need for blood transfusion. In 2011, results from a multi-center, randomized, and placebo controlled trial (CRASH-2 trial) showed that TXA (1 g loading dose over 10 min followed by an infusion of 1 g over 8 h) safely reduces mortality in bleeding trauma patients. Initiation of TXA treatment within 3 h of injury reduces the risk of hemorrhage death by about one-third, regardless of baseline risk. Because it does not have any serious adverse effects, TXA can be administered to a wide spectrum of bleeding trauma patients. Limiting its use to the most severely injured or those with a diagnosis of 'hyperfibrinolysis' would result in thousands of avoidable deaths. A clinical trial (CRASH-3 trial) of TXA in patients with traumatic brain injury is now in progress. PMID- 26149024 TI - Inherited disorders of platelet function: selected updates. AB - The gene variants responsible for the primary genotype of many platelet disorders have now been identified. Next-generation sequencing technology (NGST), mainly exome sequencing, has highlighted genes responsible for defects in platelet secretion (NBEAL2, gray platelet syndrome), procoagulant activity (STIM1, Stormorken syndrome), and activation pathways (RASGRP2, CalDAG-GEFI deficiency and integrin dysfunction; PRKACG, cyclic adenosine monophosphate-dependent protein kinase deficiency). Often disorders of platelet function are associated with a modified platelet production with changes in platelet number and size and can accompany malfunction of other organs or tissues. Most families have private mutations, and gene variants may prevent protein synthesis, abrogate function, or result in aberrant activated proteins. Nevertheless, bleeding severity is difficult to predict by genotype alone suggesting other factors. A major new challenge of NGST is to identify these factors and help improve patient care. This review concentrates on recent developments and is illustrated from personal observations. PMID- 26149025 TI - New insights into the biology of tissue factor pathway inhibitor. AB - Tissue factor pathway inhibitor (TFPI) dampens the initiation of blood coagulation by inhibiting two potent procoagulant complexes, tissue factor-factor VIIa (TF-FVIIa) and early forms of prothrombinase. TFPI isoforms, TFPIalpha and TFPIbeta, result from alternative splicing of mRNA, producing distinct C-terminal ends of the two proteins. Both isoforms inhibit TF-FVIIa, but only TFPIalpha can inhibit early forms of prothrombinase by binding of its positively charged C terminus with high affinity to the acidic B-domain exosite of FVa, which is generated upon activation by FXa. TFPIalpha and TFPIbeta are produced in cultured human endothelial cells, while platelets contain only TFPIalpha. Knowledge of the anticoagulant mechanisms and tissue expression patterns of TFPIalpha and TFPIbeta have improved our understanding of the phenotypes observed in different mouse models of TFPI deficiency, the east Texas bleeding disorder, and the development of pharmaceutical agents that block TFPI function to treat hemophilia. PMID- 26149028 TI - Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use. AB - Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. PMID- 26149027 TI - Life after acquired thrombotic thrombocytopenic purpura: morbidity, mortality, and risks during pregnancy. AB - Patients who have recovered from their acute episode of acquired ADAMTS13 deficient thrombotic thrombocytopenic purpura (TTP) were once thought to have complete recovery except for risk of relapse. Data from previous publications from the Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry are summarized. Patients have decreased cognitive function and increased prevalence of hypertension, systemic lupus erythematosus, major depression, and albuminuria as compared to the expected values from the US population. The proportion of patients that died during the follow-up period was greater than expected based on the US population reference population. Among women who had a pregnancy following recovery from TTP, relapse during pregnancy or postpartum is uncommon, but the occurrence of preeclampsia may be increased. Thirteen of 16 pregnancies in these women resulted in healthy children. Increased morbidity and mortality in TTP patients following recovery suggest that TTP may be more of a chronic disorder than a disorder with acute episodes and complete recovery. PMID- 26149026 TI - Fibrinogen, red blood cells, and factor XIII in venous thrombosis. AB - Cardiovascular disease is the leading cause of death and disability worldwide. Among cardiovascular causes of death, venous thrombosis (VT) is ranked third most common in the world. Venous thrombi have high red blood cell and fibrin content; however, the pathophysiologic mechanisms that contribute to venous thrombus composition and stability are still poorly understood. This article reviews biological, biochemical, and biophysical contributions of fibrinogen, factor XIII, and red blood cells to VT, and new evidence suggesting interactions between these components mediate venous thrombus composition and size. PMID- 26149029 TI - Spontaneous acute superficial vein thrombosis of the legs: do we really need to treat? AB - Spontaneous acute superficial vein thrombosis (SVT) of the leg is now generally recognized as an integral component of venous thromboembolic disease with potentially severe consequences. However, the relatively low grades of some current international recommendations and uncertainty regarding the cost effectiveness of available therapies may prompt questioning of the real need to treat patients with SVT and explain the persisting heterogeneity of their management in practise. Yet several studies have consistently shown high rates of thromboembolic complications associated with SVT, whether at first presentation or during follow-up. The CALISTO trial established for the first time the clinical benefit of a well-defined anticoagulant regimen for the prevention of serious thromboembolic complications in SVT patients, and we believe that patients such as those included in this trial should receive this regimen as tested. However, several areas of uncertainty remain for categories of SVT patients not evaluated in CALISTO. PMID- 26149030 TI - Cerebral venous thrombosis. AB - Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults and children. In contrast to venous thromboembolism, women are affected three times more often than men. Baseline symptoms can vary considerably between patients, but most present with headache, seizures, or focal neurological deficits. Patients can be diagnosed with magnetic resonance imaging, computerized tomography-venography, or catheter angiography, although the latter is rarely required anymore. Approximately 30-50% of patients have an intracerebral hemorrhage, which can range from a small juxtacortical hemorrhage to large space-occupying lesions. Based on limited evidence from clinical trials, the primary therapy for CVT is anticoagulation with heparin. Uncontrolled studies have shown promising results for the use of endovascular treatment in severely affected patients, but these studies require confirmation in prospective clinical trials. In patients who develop clinical and radiological signs of impending herniation decompressive surgery can be both life saving and result in a good functional outcome. PMID- 26149031 TI - Interventional therapy for venous thromboembolism. AB - Advances in image-guided, catheter-based interventions have shown great potential to improve outcomes in patients with venous thromboembolism. Catheter-directed thrombolysis has been shown in one randomized controlled trial to reduce the risk of post-thrombotic syndrome in patients with acute lower extremity deep vein thrombosis; data from a larger national institute of health trial are expected in early 2017. The use of catheter-directed thrombolysis is also being increasingly considered for patients with submassive or massive pulmonary embolism. Preliminary studies suggest that endovascular stent placement and ablative therapies may be used to reduce symptoms and improve quality of life in severely affected patients with established post-thrombotic syndrome. In this article, we summarize the risks and benefits of endovascular venous thromboembolism therapies as currently understood, highlight clinical situations where their benefit may outweigh risks, and describe ongoing and upcoming pivotal research initiatives with multidisciplinary participation. PMID- 26149032 TI - Pulmonary embolism: whom to discharge and whom to thrombolyze? AB - Patients with pulmonary embolism can be divided in two groups according to their risk of death or major complication: a small group of high-risk patients defined by the presence of systemic hypotension or cardiogenic shock and a large group of normotensive patients. Among normotensive patients, further risk stratification, based on clinical grounds alone or on the combination of clinical data, biomarkers, and imaging tests, allows selection of low-risk patients and intermediate-risk patients. The safety of outpatient treatment for low-risk patients has been established mainly on the basis of retrospective and prospective cohorts using different selection tools. In most studies, about 50% of the patients have been safely treated at home. Although thrombolytic therapy has a favorable benefit to risk profile in patients with high-risk pulmonary embolism, the risk of major and especially intracranial bleeding outweighs the benefits in terms of hemodynamic decompensation in patients with intermediate risk pulmonary embolism. PMID- 26149033 TI - Controversies in the diagnosis of venous thromboembolism. AB - Over the last decades, important advances have been made in the diagnosis of venous thromboembolism (VTE). Current diagnostic strategies rely on the sequential use of non-invasive diagnostic tests, based on the pretest clinical probability of disease. Diagnostic tests include D-dimer measurement, leg vein compression ultrasonography, chest computed tomography pulmonary angiography, or ventilation perfusion (V/Q) lung scan. The safety and cost-effectiveness of these strategies have been extensively validated. They have been widely implemented in clinical practice and have replaced the historical gold standard diagnostic tests (venography and pulmonary angiography). However, new challenges arise, including a lower clinical suspicion threshold and concerns on potential over-diagnosis of VTE. Moreover, the diagnostic management remains suboptimal in many subgroups of patients with suspected VTE: patients with prior VTE, pregnant women, or elderly patients. PMID- 26149035 TI - Warfarin pharmacogenomics: current best evidence. AB - The utility of using genetic information to guide warfarin dosing has remained unclear based on prior observational studies and small clinical trials. Two larger trials of warfarin and one of the acenocoumarol and phenprocoumon have recently been published. The COAG trial addressed the incremental benefit of adding genetic information to clinical information and demonstrated no benefit from the pharmacogenetic-based dosing strategy on the primary outcome. The EU PACT UK trial compared an algorithm approach using genetic and clinical information to one that used a relatively fixed starting dose. The pharmacogenetic-based algorithms improved the primary outcome. The study of acenocoumarol and phenprocoumon compared a pharmacogenetic with a clinical algorithm and demonstrated no benefit on the primary outcome. The evidence to date does not support an incremental benefit of adding genetic information to clinical information on anticoagulation control. However, compared with fixed dosing, a pharmacogenetic algorithm can improve anticoagulation control. PMID- 26149034 TI - Regulation of the genetic code in megakaryocytes and platelets. AB - Platelets are generated from nucleated precursors referred to as megakaryocytes. The formation of platelets is one of the most elegant and unique developmental processes in eukaryotes. Because they enter the circulation without nuclei, platelets are often considered simple, non-complex cells that have limited functions beyond halting blood flow. However, emerging evidence over the past decade demonstrates that platelets are more sophisticated than previously considered. Platelets carry a rich repertoire of messenger RNAs (mRNAs), microRNAs (miRNAs), and proteins that contribute to primary (adhesion, aggregation, secretion) and alternative (immune regulation, RNA transfer, translation) functions. It is also becoming increasingly clear that the 'genetic code' of platelets changes with race, genetic disorders, or disease. Changes in the 'genetic code' can occur at multiple points including megakaryocyte development, platelet formation, or in circulating platelets. This review focuses on regulation of the 'genetic code' in megakaryocytes and platelets and its potential contribution to health and disease. PMID- 26149036 TI - Acute and persistent platelet and coagulant activities in atherothrombosis. AB - The potential relevance of murine atherothrombosis models for understanding human disease has been debated in the past. Despite this, in the last decade, many thrombosis studies with atherogenic Apoe(-/-) mice have been performed, which provide novel insight into the molecular mechanisms by which platelet and coagulation processes accomplish acute thrombus formation after plaque disruption in vivo. Support for these mechanisms has come from whole blood flow perfusion studies over plaque material in vitro, which are also reviewed in this study. The main plaque-derived triggers for thrombus formation appear to be collagen and tissue factor, next to bioactive mediators such as prostaglandin E2. The atherothrombotic process relies on collagen- and ADP-receptor-induced platelet activation as well as on thrombin/fibrin generation via the extrinsic and intrinsic coagulation pathways. Less is known of the persistent effects of a thrombus on atherosclerosis progression, but evidence suggests roles herein of activated platelets and ongoing thrombin generation. PMID- 26149037 TI - Use of genetic data to guide therapy in arterial disease. AB - There is considerable interindividual variation in the response to antiplatelet and anticoagulant therapies. It has been proposed that this variability in drug response may be attributable to genetic variants. Thus, pharmacogenetics may help to accurately predict response to cardiovascular disease (CVD) therapies in order to maximize drug efficacy, minimize drug toxicity, and to tailor personalized care for these patients. Although the clinical utility of pharmacogenetics is promising, its adoption in clinical practice has been slow. This resistance may stem from sometimes conflicting findings among pharmacogenetic studies. Thus, this review focuses on the genetic determinants of commonly used platelet antagonists and anticoagulants including aspirin, clopidogrel, dabigatran, and warfarin. We also explore the clinical translation of pharmacogenetics in the management of patients with CVD. PMID- 26149038 TI - Treatment of acute ischemic stroke: from fibrinolysis to neurointervention. AB - Thrombolytic therapy with intravenous recombinant tissue plasminogen activator is well established as a beneficial treatment for patients presenting with acute ischemic stroke (AIS). The odds of a favorable clinical outcome (living independently) increase as the time between stroke onset and treatment with IV thrombolysis decreases. However, many patients present with a large clot burden that seldom responds to systemic fibrinolysis. Alternative options include new and emerging endovascular therapies that have recently proven effectiveness at restoring cerebral blood flow to the ischemic brain parenchyma. This review article will briefly outline some of the key evidence for intravenous thrombolysis as well as endovascular therapy for AIS. PMID- 26149039 TI - Role of aspirin for prevention and treatment of perioperative cardiovascular events. AB - Among adults undergoing non-cardiac surgery who are at risk of a myocardial infarction, a long-standing question has been whether these patients should receive aspirin throughout the perioperative period. A large (n = 10,010 patients) international trial (POISE-2) demonstrated that perioperative aspirin did not prevent myocardial infarction, and the result was consistent both for patients who had been taking aspirin before the trial (continuation stratum, 4382 patients) and for patients who had not been taking aspirin before the trial (initiation stratum, 5628 patients). Aspirin did, however, increase the risk of major bleeding. Therefore, the best evidence does not support the use of aspirin for the prevention of myocardial infarction in patients undergoing non-cardiac surgery. In patients who have an indication for long-term aspirin usage and have their aspirin held during the perioperative period, it is important to ensure aspirin is restarted after the high-risk period for bleeding has passed (i.e., 8 10 days after surgery). PMID- 26149040 TI - Postoperative atrial fibrillation in non-cardiac and cardiac surgery: an overview. AB - Postoperative atrial fibrillation (POAF) is the most common perioperative cardiac arrhythmia. A major risk factor for POAF is advanced age, both in non-cardiac and cardiac surgery. Following non-cardiac surgery, it is important to correct reversible conditions such as electrolytes imbalances to prevent the occurrence of POAF. Management of POAF consists of rate control and therapeutic anticoagulation if POAF persists for > 48 h and CHADS2 score > 2. After cardiac surgery, POAF affects a larger amount of patients. In addition to age, valve surgery carries the greatest risk for new AF. Rate control is the mainstay therapy in these patients. Prediction, prevention, and management of POAF should be further studied. PMID- 26149041 TI - Antiplatelet drugs: which targets for which treatments? AB - The current standard care for acute coronary syndromes is dual antiplatelet therapy combining the COX1 inhibitor aspirin with a drug targeting the P2Y12 receptor, together with anticoagulation during and after early revascularization by percutaneous intervention. In very high-risk patients, glycoprotein (GP) IIb/IIIa antagonists may also be used. Secondary prevention of ischemic events requires dual antiplatelet therapy for several months followed by lifelong low dose aspirin. The duration of treatment and the drugs to combine nevertheless remain matters of debate and the focus of ongoing research. Despite great progress, there is still room for improved efficacy and this could involve new targets for both antiplatelet drugs (like the thrombin receptor PAR1) and anticoagulants. However, improved efficacy is offset by an increased risk of bleeding. Stroke patients are still waiting for better treatment, their bleeding risk being particularly high. New targets including the collagen receptor, glycoprotein VI (GPVI), and the GPIb-von Willebrand factor axis, governing platelet interaction with the diseased vessel wall, should enable us to complete the armamentarium of antiplatelet drugs. PMID- 26149042 TI - Proteomic signatures of antiplatelet drugs: new approaches to exploring drug effects. AB - Antiplatelet agents represent the mainstay of acute coronary syndrome (ACS) therapy to prevent ischemic events and to improve safety in patients undergoing percutaneous coronary intervention. However, despite the availability of several drugs and the use of dual antiplatelet therapy, the pharmacological response is highly variable with a subset of patients continuing to experience recurrent thrombotic events, revealing a wide variability in platelet response to antiplatelet drugs. Several factors may explain this, including genetic variation and environmental factors. Here we look at the application of proteomic analysis, an approach that provides an integrated readout of these diverse influences. PMID- 26149043 TI - The role of circulating platelet transcripts. AB - Our understanding of platelets, anucleate cells with a traditional role in hemostasis and inflammation, has developed greatly over the last decade. Platelets' role in the systemic response of the body to vascular injury, inflammation, and infection has expanded as has our understanding of their importance to the body's regulation of these processes. One recently explored mechanism by which platelets regulate the body's inflammatory and immune response is through its endogenous RNA. Platelets' messenger RNA (mRNAs) and microRNA (miRNAs) profiles have been shown to reflect disease and disease risk factors and have been correlated with select human clinical phenotypes. Developing an understanding of platelet transcripts in the circulation elucidates how platelets function in both their traditional thrombotic role and non-traditional functions and may have widespread implications in several fields including thrombosis, infection, cancer, and systemic inflammation. PMID- 26149044 TI - Triple therapy for percutaneous coronary intervention in atrial fibrillation: standard of care, or a nightmare soon to end? AB - The need to combine anticoagulant and antiplatelet therapy ('triple therapy') in patients with atrial fibrillation and coronary artery disease increases the risk of bleeding. As percutaneous intervention is now the dominant therapy for coronary disease, clinicians question how to manage the risk of stroke in patients with atrial fibrillation and a coronary stent that require dual antiplatelet therapy. In this review, the risk of stroke and coronary thrombosis in this difficult group of patients will be summarized using current recommendations and guidelines. The scarce randomized data on triple therapy are reviewed, and there will be a focus on currently running trials on this topic. PMID- 26149045 TI - Extracorporeal life support: the precarious balance of hemostasis. AB - Extracorporeal life support is by far the most extraordinary and complex form of extracorporeal technology used in the practice of critical care medicine. It is used to support critically ill patient who suffer acute respiratory or cardiac failure unresponsive to conventional support. As extracorporeal technologies have refined the pathophysiologic reaction that occurs at the blood/biomaterial interface has not been conquered; a new set of physiologic responses/derangements occur with the patient's exposure to the artificial circuit. Without this support mortality is near certain and with support if management is not precise and judicious the complications can be catastrophic. The management of a patient on ECLS is the same as for any critically ill patient with the added need for anticoagulation to maintain patency of the extracorporeal circuit without causing bleeding within the patient and thrombosis within the circuitry or the patient. This is the precarious balance of hemostasis during ECLS. PMID- 26149046 TI - Antithrombotic therapy for ventricular assist devices in children: do we really know what to do? AB - The use of ventricular assist devices (VADs) in children is increasing. Stroke and device-related thromboembolism remain the most feared complications associated with VAD therapy in children. The presence of a VAD causes dysregulation of hemostasis due to the presence of foreign materials and sheer forces intrinsic to the device resulting in hypercoagulability and potentially life-threatening thrombosis. The use of antithrombotic therapy in adults with VADs modulates this disruption in hemostasis, decreasing the risk of thrombosis. Yet, differences in hemostasis in children (developmental hemostasis) may result in variances in dysregulation by these devices and preclude the use of adult guidelines. Consequently, pediatric device studies must include safety and efficacy estimates of device-specific antithrombotic therapy guidelines. This review will discuss mechanisms of hemostatic dysregulation as it pertains to VADs, goals of VAD antithrombotic therapy for children and adults, and emerging antithrombotic strategies for VAD use in children. PMID- 26149047 TI - Pediatric transplantation: preventing thrombosis. AB - Due to progressive advances in surgical techniques, immunosuppressive therapies, and supportive care, outcomes from both solid organ transplantation and hematopoietic stem cell transplantation continue to improve. Thrombosis remains a challenging management issue in this context, with implications for both graft survival and long-term quality of life. Unfortunately, there remains a general paucity of pediatric-specific data regarding thrombosis incidence, risk stratification, and the safety or efficacy of preventative strategies with which to guide treatment algorithms. This review summarizes the available evidence and rationale underlying the spectrum of current practices aimed at preventing thrombosis in the transplant recipient, with a particular focus on risk factors, pathophysiology, and described antithrombotic regimens. PMID- 26149048 TI - Pediatric transplantation: managing bleeding. AB - There has been extraordinary progress over the last half-century in the field of medical transplantation in which tissue, organs, or body parts from one human are placed into another. Solid organ transplants have allowed thousands of children with otherwise devastating inherited or acquired disorders to survive. Depending upon the clinical situation, there are many specific peri-transplant issues that must be carefully addressed to optimize outcomes. Although surgical, immunologic, and infectious concerns are usually in the forefront, important aspects regarding hemostasis frequently arise. The number of solid organs that can be successfully transplanted in children has expanded over the last decades and includes kidney, liver, heart, lung, intestine, pancreas, and thymus. Bleeding complications may occur in the setting of organ failure prior to transplantation, during the surgical procedure, or in the post-transplant setting, and can results in significant morbidity. This report will focus on preventing and managing non surgical-related bleeding complications in children undergoing liver, heart, kidney transplantation, in whom there are often unique aspects of coagulation to be considered. PMID- 26149049 TI - Platelets and their microparticles as key players in pathophysiological responses. AB - Platelets are known to play a central role in primary hemostasis as well as in the pathophysiology of thrombotic disorders. However, in addition to hemostasis, platelets are involved in a variety of pathophysiological responses including immune responses, inflammation, angiogenesis, tissue regeneration, and cancer metastasis. Recent studies revealed a significant role for platelet-derived microparticles (PMP), in these responses. PMP communicate with, and deliver signals to, other cells, induce signals, and change their phenotype during inflammation, angiogenesis, and tumor metastasis. The current report describes the recent development in this field with a focus on the role of platelets and PMP in all of the above responses. PMID- 26149050 TI - Manipulating megakaryocytes to manufacture platelets ex vivo. AB - Historically, platelet transfusion has proven a reliable way to treat patients suffering from thrombocytopenia or similar ailments. An undersupply of donors, however, has demanded alternative platelet sources. Scientists have therefore sought to recapitulate the biological events that convert hematopoietic stem cells into platelets in the laboratory. Such platelets have shown good function and potential for treatment. Yet the number manufactured ex vivo falls well short of clinical application. Part of the reason is the remarkable gaps in our understanding of the molecular mechanisms driving platelet formation. Using several stem cell sources, scientists have progressively clarified the chemical signaling and physical microenvironment that optimize ex vivo platelets and reconstituted them in synthetic environments. Key advances in cell reprogramming and the ability to propagate self-renewal have extended the lifetime of megakaryocytes to increase the pool of platelet progenitors. PMID- 26149051 TI - Road blocks in making platelets for transfusion. AB - The production of laboratory-generated human platelets is necessary to meet present and future transfusion needs. This manuscript will identify and define the major roadblocks that must be overcome to make human platelet production possible for clinical use, and propose solutions necessary to accelerate development of laboratory-generated human platelets to market. PMID- 26149053 TI - Medical device-induced thrombosis: what causes it and how can we prevent it? AB - Blood-contacting medical devices, such as vascular grafts, stents, heart valves, and catheters, are often used to treat cardiovascular diseases. Thrombus formation is a common cause of failure of these devices. This study (i) examines the interface between devices and blood, (ii) reviews the pathogenesis of clotting on blood-contacting medical devices, (iii) describes contemporary methods to prevent thrombosis on blood-contacting medical devices, (iv) explains why some anticoagulants are better than others for prevention of thrombosis on medical devices, and (v) identifies future directions in biomaterial research for prevention of thrombosis on blood-contacting medical devices. PMID- 26149052 TI - TACTIC: Trans-Agency Consortium for Trauma-Induced Coagulopathy. AB - Trauma-induced coagulopathy (TIC) includes heterogeneous coagulopathic syndromes with different underlying causes, and treatment is challenged by limited diagnostic tests to discriminate between these entities in the acute setting. We provide an overview of progress in understanding the mechanisms of TIC and the context for several of the hypotheses that will be tested in 'TACTIC'. Although connected to ongoing clinical trials in trauma, TACTIC itself has no intent to conduct clinical trials. We do anticipate that 'early translation' of promising results will occur. Functions anticipated at this early translational level include: (i) basic science groundwork for future therapeutic candidates; (ii) development of acute coagulopathy scoring systems; (iii) coagulation factor composition-based computational analysis; (iv) characterization of novel analytes including tissue factor, polyphosphates, histones, meizothrombin and alpha thrombin-antithrombin complexes, factor XIa, platelet and endothelial markers of activation, signatures of protein C activation and fibrinolysis markers; and (v) assessment of viscoelastic tests and new point-of-care methods. PMID- 26149054 TI - Extracellular DNA and histones: double-edged swords in immunothrombosis. AB - The existence of extracellular DNA in human plasma, also known as cell-free DNA (cfDNA), was first described in the 1940s. In recent years, there has been a resurgence of interest in the functional significance of cfDNA, particularly in the context of neutrophil extracellular traps (NETs). cfDNA and histones are key components of NETs that aid in the host response to infection and inflammation. However, cfDNA and histones may also exert harmful effects by triggering coagulation, inflammation, and cell death and by impairing fibrinolysis. In this article, we will review the pathologic nature of cfDNA and histones in macrovascular and microvascular thrombosis, including venous thromboembolism, cancer, sepsis, and trauma. We will also discuss the prognostic value of cfDNA and histones in these disease states. Understanding the molecular and cellular pathways regulated by cfDNA and histones may provide novel insights to prevent pathological thrombus formation and vascular occlusion. PMID- 26149056 TI - Basic mechanisms and regulation of fibrinolysis. AB - Fibrinolysis appears in many diverse physiological situations, and the components of the system are well established, along with mechanistic details for the individual reactions and some high-resolution structures. Key questions in understanding the regulation of fibrinolysis surround mechanisms of initiation and propagation, the localization of fibrinolysis reactions to the fibrin clot, and the influence of fibrin structure and clot composition on thrombolysis. This review covers these key areas with a focus on recent developments on fibrin structure and binding, the effects of a variety of cell types, the consequences of histones and DNA released by neutrophils, and the influence of flow. A complete understanding of the regulation of fibrinolysis will come from the building of detailed mathematical models. Suitable models are at an early stage of development, but may improve as model clots increase in complexity to incorporate the components and interactions listed above. PMID- 26149055 TI - Polyphosphate as modulator of hemostasis, thrombosis, and inflammation. AB - Inorganic polyphosphate (polyP), a linear polymer of phosphates, is present in many infectious microorganisms and is secreted by mast cells and platelets. PolyP has recently been shown to accelerate blood clotting and slow fibrinolysis, in a manner that is highly dependent on polymer length. Very long-chain polyP (of the type present in microorganisms) is an especially potent trigger of the contact pathway, enhances the proinflammatory activity of histones, and may participate in host responses to pathogens. PolyP also inhibits complement, providing another link between polyP and inflammation/innate immunity. Platelet-size polyP (which is considerably shorter) accelerates factor V activation, opposes the anticoagulant action of tissue factor pathway inhibitor, modulates fibrin clot structure, and promotes factor XI activation. PolyP may have utility in treating bleeding. It is also a potential target for the development of antithrombotic drugs with a novel mechanism of action and potentially fewer bleeding side effects compared with conventional anticoagulants. PMID- 26149057 TI - [Optimal duration of dual antiplatelet therapy]. PMID- 26149058 TI - [Anamnesis and their relevance, a case report: Popliteal fossa mass]. PMID- 26149059 TI - [Is the antibiotic prophylaxis necessary for the prevention of infective endocarditis?]. PMID- 26149060 TI - [Community acquired Pseudomonas aeruginosa respiratory infection in a patient with Steinert's disease and hypogammaglobulinemia]. PMID- 26149061 TI - [Erythema nodosum of atypical location]. PMID- 26149062 TI - Band-sensitive seizure onset detection via CSP-enhanced EEG features. AB - This paper presents two novel epileptic seizure onset detectors. The detectors rely on a common spatial pattern (CSP)-based feature enhancement stage that increases the variance between seizure and nonseizure scalp electroencephalography (EEG). The proposed feature enhancement stage enables better discrimination between seizure and nonseizure features. The first detector adopts a conventional classification stage using a support vector machine (SVM) that feeds the energy features extracted from different subbands to an SVM for seizure onset detection. The second detector uses logical operators to pool SVM seizure onset detections made independently across different EEG spectral bands. The proposed detectors exhibit an improved performance, with respect to sensitivity and detection latency, compared with the state-of-the-art detectors. Experimental results have demonstrated that the first detector achieves a sensitivity of 95.2%, detection latency of 6.43s, and false alarm rate of 0.59perhour. The second detector achieves a sensitivity of 100%, detection latency of 7.28s, and false alarm rate of 1.2per hour for the MAJORITY fusion method. PMID- 26149063 TI - Breaking bad news on the possible occurrence of sudden death in children with epilepsy sleeping on sofas. PMID- 26149064 TI - Dentine scattering, absorption, transmittance and light reflectivity in human incisors, canines and molars. AB - OBJECTIVES: To evaluate, using Kubelka-Munk reflectance theory, the scattering (S), absorption (K), transmittance (T) and light reflectivity (RI) of incisors, canines and molars human dentine. METHODS: Eighty-one human teeth (incisors, canines and molars) were used in this study. All teeth crowns were sectioned using a water-cooled diamond saw at low speed. The obtained dentine samples were polished to a final thickness of 2mm. The relative spectral radiance was measured against black and white backgrounds, using a spectroradiometer in a viewing cabinet with D65 illuminant. Kubelka-Munk equations were used to calculate the scattering and absorption coefficients, transmittance and light reflectivity. Kruskal-Wallis rank sum test was performed to compare the mean values of Kubelka Munk coefficients of human incisors, canines and molars dentine samples followed by Kruskal-Wallis multiple comparison tests for pairwise comparisons. RESULTS: The spectral behavior of S, T and RI exhibited similar trends for all three types of dentine samples. However, highly significant differences (p<0.001) were found between their magnitudes in the three types of dentine samples (p<0.001). Only the magnitudes of the K coefficients were found to be similar (p=0.235) between incisors, canines and molars. Canine's dentine samples showed highest S and RI values, while human molars dentine samples exhibited highest K and T values. CONCLUSIONS: Within the limitations of this study, the optical properties of human dentine are strongly influenced by the type of tooth. The results of the present study can be used as reference in the development of aesthetic dental restorative materials. CLINICAL IMPLICATIONS: The significant differences identified in the optical behavior of the dentine from the three types of teeth have to be taken into consideration by the dentist and the dental technician when pursuing biomimetics with any restorative material in esthetic dentistry. PMID- 26149065 TI - The effect of a fiber reinforced cavity configuration on load bearing capacity and failure mode of endodontically treated molars restored with CAD/CAM resin composite overlay restorations. AB - OBJECTIVES: To evaluate the fracture strength and the mode of failure of endodontically treated molars restored with CAD/CAM overlays with fiber reinforced composite build-up of the pulp chamber. METHODS: 40 Devitalized molars were cut over the CEJ and divided into five groups (n=8). The pulp chamber area was filled with: group 0 (control), no resin build-up; group 1, hybrid composite build-up (G-aenial posterior, GC); group 2, as in group 1 but covered with 3 nets of bi-directional E-glass fibers (EverStickNET, Stick Tech Ltd.); group 3, a FRC resin (EverX posterior, GC); group 4, as in group 3 but covered by the bi directional fibers. The crowns were restored with CAD-CAM composite restorations (Lava Ultimate, 3M ESPE). Maximum fracture loads were recorded in Newton and data were analyzed using Kruskal-Wallis test (p<0.05). Fragments were analyzed using SEM. RESULTS: The mean static loads in Newton were: group 0: 2448 (546); group 1: 2817 (873); group 2: 2128 (952); group 3: 2429 (1091); group 4: 2577 (833). No significant differences were found between the groups (p>0.05). All specimens fractured in a catastrophic way, under the CEJ. The main crack evolved in the corono-apical direction. In groups 2 and 4 secondary fracture paths with apico coronal direction were detected close to the bi-directional fibers' layer. CONCLUSIONS: For the restoration of endodontically treated molars, the incorporation of FRCs did not influence the load-bearing capacity of the tooth restoration complex. The SEM analysis showed a low ability of the bi-directional fibers net in deviating the fracture but this effect was not sufficient to lead more favorable fracture patterns, over the CEJ. CLINICAL SIGNIFICANCE: The use of FRCs to reinforce the "core" of devitalized molars against vertical fractures under static loads seems useless when the thickness of the CAD/CAM composite overlay restoration is high. PMID- 26149066 TI - Applying precision medicine to the active surveillance of prostate cancer. AB - The recent introduction of a variety of molecular tests will potentially reshape the care of patients with prostate cancer. These tests may make more accurate management decisions possible for those patients who have been "overdiagnosed" with biologically indolent disease, which represents an exceptionally small mortality risk. There is a wide range of possible applications of these tests to different clinical scenarios in patient populations managed with active surveillance. Cancer 2015;121:3435-43. (c) 2015 American Cancer Society. PMID- 26149067 TI - Single Nanoparticle Detection Using Far-field Emission of Photonic Molecule around the Exceptional Point. AB - Highly sensitive, label-free detection methods have important applications in fundamental research and healthcare diagnostics. To date, the detection of single nanoparticles has remained largely dependent on extremely precise spectral measurement, which relies on high-cost equipment. Here, we demonstrate a simple but very nontrivial mechanism for the label-free sizing of nanoparticles using the far-field emission of a photonic molecule (PM) around an exceptional point (EP). By attaching a nanoparticle to a PM around an EP, the main resonant behaviors are strongly disturbed. In addition to typical mode splitting, we find that the far-field pattern of the PM is significantly changed. Taking a heteronuclear diatomic PM as an example, we demonstrate that a single nanoparticle, whose radius is as small as 1 nm to 7 nm, can be simply monitored through the variation of the far-field pattern. Compared with conventional methods, our approach is much easier and does not rely on high-cost equipment. In addition, this research will illuminate new advances in single nanoparticle detection. PMID- 26149069 TI - Stability of Polymer Ultrathin Films (<7 nm) Made by a Top-Down Approach. AB - In polymer physics, the dewetting of spin-coated polystyrene ultrathin films on silicon remains mysterious. By adopting a simple top-down method based on good solvent rinsing, we are able to prepare flat polystyrene films with a controlled thickness ranging from 1.3 to 7.0 nm. Their stability was scrutinized after a classical annealing procedure above the glass transition temperature. Films were found to be stable on oxide-free silicon irrespective of film thickness, while they were unstable (<2.9 nm) and metastable (>2.9 nm) on 2 nm oxide-covered silicon substrates. The Lifshitz-van der Waals intermolecular theory that predicts the domains of stability as a function of the film thickness and of the substrate nature is now fully reconciled with our experimental observations. We surmise that this reconciliation is due to the good solvent rinsing procedure that removes the residual stress and/or the density variation of the polystyrene films inhibiting thermodynamically the dewetting on oxide-free silicon. PMID- 26149068 TI - Biological behavior of mesenchymal stem cells on poly-epsilon-caprolactone filaments and a strategy for tissue engineering of segments of the peripheral nerves. AB - INTRODUCTION: Peripheral nerves may fail to regenerate across tube implants because these lack the microarchitecture of native nerves. Bone marrow mesenchymal stem cells (MSC) secrete soluble factors that improve the regeneration of the peripheral nerves. Also, microstructured poly-caprolactone (PCL) filaments are capable of inducing bands of Bungner and promote regeneration in the peripheral nervous system (PNS). We describe here the interaction between PCL filaments and MSC, aiming to optimize PNS tubular implants. METHODS: MSC were plated on PCL filaments for 48 h and the adhesion profile, viability, proliferation and paracrine capacity were evaluated. Also, Schwann cells were plated on PCL filaments covered with MSC for 24 h to analyze the feasibility of the co-culture system. Moreover, E16 dorsal root ganglia were plated in contact with PCL filaments for 4 days to analyze neurite extension. Right sciatic nerves were exposed and a 10 mm nerve segment was removed. Distal and proximal stumps were reconnected inside a 14-mm polyethylene tube, leaving a gap of approximately 13 mm between the two stumps. Animals then received phosphate-buffered saline 1*, PCL filaments or PCL filaments previously incubated with MSC and, after 12 weeks, functional gait performance and histological analyses were made. Statistical analyses were made using Student's unpaired t-test, one-way analysis of variance (ANOVA) or two-way ANOVA followed by Bonferroni post-test. RESULTS: MSC were confined to lateral areas and ridges of PCL filaments, aligning along the longitudinal. MSC showed high viability (90 %), and their proliferation and secretion capabilities were not completely inhibited by the filaments. Schwann cells adhered to filaments plated with MSC, maintaining high viability (90 %). Neurites grew and extended over the surface of PCL filaments, reaching greater distances when over MSC-plated filaments. Axons showed more organized and myelinized fibers and reinnervated significantly more muscle fibers when they were previously implanted with MSC-covered PLC filaments. Moreover, animals with MSC-covered filaments showed increased functional recovery after 12 weeks. CONCLUSIONS: We provide evidence for the interaction among MSC, Schwann cells and PCL filaments, and we also demonstrate that this system can constitute a stable and permissive support for regeneration of segments of the peripheral nerves. PMID- 26149070 TI - The prevalence and related factors of depressive symptoms among junior college nursing students: a cross-sectional study. AB - Nursing students have particularly experienced stressful lives during nursing education. This cross-sectional study aimed to investigate depressive symptoms and related factors in junior college nursing students. A total of 625 nursing students from a junior college in Taiwan were assessed by Pittsburgh Sleep Quality Index, Adolescent Depression Inventory, Situational Anxiety Scale and the Taiwanese-Chinese version of Stress in Nursing Students Scale. The results showed that (1) the prevalence of depressive symptoms among junior college nursing students was 32.6%; (2) depressive symptoms are significantly related to grade point average, interest in nursing, interest in their clinical placement, career planning after graduation, overeating as a stress-relief strategy, sleep problems, stress, and anxiety; and (3) anxiety, sleep quality, and stress are three major variables that can significantly predict depressive symptoms. Psychological factors may influence young nursing students' willingness to seek assistance from teachers. These factors should be considered when designing strategies to promote their emotional health and well-being. Nursing educators can plan appropriate strategies tailored to junior college nursing students' problems and needs, which thereby may facilitate learning experience and prevent depressive symptoms. PMID- 26149071 TI - Staying on the job: The relationship between work performance and cognition in individuals diagnosed with multiple sclerosis. AB - People with multiple sclerosis (MS) are apt to become unemployed as the disease progresses, and most research implies that this is due to diminishing mobility. Some studies have shown that presence of cognitive impairment also predicts employment status. Yet, no studies have examined how neuropsychological factors predict vocational performance among individuals with MS who remain employed. We assessed employer- and self-rated work performance, mobility status, and neuropsychological function in a sample of 44 individuals diagnosed with MS. Results suggest that cognitive impairment is common in these employed individuals, despite largely intact mobility status. Moreover, a significant interaction emerged, such that cognitively impaired individuals' work performance was rated more poorly by supervisors. In contrast, self-ratings of work performance were higher in cognitively impaired than in unimpaired participants. These novel findings suggest that cognitive impairment may influence work performance, even in patients whose physical disability status is relatively intact. PMID- 26149072 TI - Differential gene expression between hygienic and non-hygienic honeybee (Apis mellifera L.) hives. AB - BACKGROUND: Hygienic behavior is a complex, genetically-based quantitative trait that serves as a key defense mechanism against parasites and diseases in Apis mellifera. Yet, the genomic basis and functional pathways involved in the initiation of this behavior are still unclear. Deciphering the genomic basis of hygienic behavior is a prerequisite to developing an extensive repertoire of genetic markers associated to the performance level of this quantitative trait. To fill this knowledge gap, we performed an RNA-seq on brain samples of 25 honeybees per hives from five hygienic and three non-hygienic hives. RESULTS: This analysis revealed that a limited number of functional genes are involved in honeybee hygienic behavior. The genes identified, and especially their location in the honeybee genome, are consistent with previous findings. Indeed, the genomic sequences of most differentially expressed genes were found on the majority of the QTL regions associated to the hygienic behavior described in previous studies. According to the Gene Ontology annotation, 15 genes are linked to the GO-terms DNA or nucleotide binding, indicating a possible role of these genes in transcription regulation. Furthermore, GO-category enrichment analysis revealed that electron carrier activity is over-represented, involving only genes belonging to the cytochrome P450. Cytochrome P450 enzymes' overexpression can be explained by a disturbance in the regulation of expression induced by changes in transcription regulation or sensitivity to xenobiotics. Over-expressed cytochrome P450 enzymes could potentially degrade the odorant pheromones or chemicals that normally signal the presence of a diseased brood before activation of the removal process thereby inhibit hygienic behavior. CONCLUSIONS: These findings improve our understanding on the genetics basis of the hygienic behavior. Our results show that hygienic behavior relies on a limited set of genes linked to different regulation patterns (expression level and biological processes) associated with an over-expression of cytochrome P450 genes. PMID- 26149073 TI - Sequence analysis of genes mediating extended-spectrum beta-lactamase (ESBL) production in isolates of Enterobacteriaceae in a Lagos Teaching Hospital, Nigeria. AB - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) in Gram-negative organisms is now a major concern in Enterobacteriaceae worldwide. This study determined a point-prevalence and genetic profiles of ESBL-producing isolates among members of the family Enterobacteriaceae in Lagos State University Teaching Hospital Ikeja, Nigeria. METHODS: Consecutive non-repetitive invasive multidrug-resistant isolates of the family Enterobacteriaceae obtained over a period of 1 month (October 2011) were studied. The isolates were identified using VITEK-2/VITEK MS Systems. Susceptibility testing was performed using E test technique; results were interpreted according to the criteria recommended by the Clinical and Laboratory Standards Institute (CLSI, 2012). ESBL production was detected by E test ESBL method and confirmed by polymerase chain reaction (PCR). RESULTS: During the one-month study period, 38 isolates with ESBL phenotypic characteristics were identified and confirmed by PCR. Of these, 21 (55.3 %) were E. coli, 12 (31.6 %) K. pneumoniae, 3 (7.9 %) Proteus spp., 1 (2.6 %) each M. morganii and C. freundii. Thirty (79 %) harbored bla CTX-M genes. Sequence analysis revealed that they were all bla CTX-M-15 genes. Twenty-nine (96.7 %) of these, also harbored bla TEM genes simultaneously. All the CTX-M-15-producing isolates carried insertion sequence bla ISEcP1 upstream of bla CTX-M-15 genes. The E. coli isolates were genetically heterogeneous, while the K. pneumoniae had 98 % homology. CONCLUSIONS: Our point-prevalence surveillance study revealed a high prevalence of Enterobacteriaceae isolates harboring bla CTX-M-15 in the Hospital. Urgent implementation of antibiotic stewardship and other preventive strategies are necessary at this time in our hospital. PMID- 26149074 TI - Heterologous murine and bovine IVF using bottlenose dolphin (Tursiops truncatus) spermatozoa. AB - Assisted reproductive technologies are of great importance for increasing the genetic diversity in captive animals. The use of bovine or murine oocytes in heterologous IVF provides advantages compared to homologous IVF in nondomestic animals, such as the accessibility to oocytes and the availability of well developed in vitro maturation systems. The aim of this study was to determine the heterologous IVF parameters using cryopreserved dolphin spermatozoa and zona intact bovine or murine oocytes and to examine the nuclear chromatin status of the dolphin spermatozoa. All the processes involved in the fertilization including embryo cleavage were observed by confocal microscopy and hybrid embryo formation was confirmed by polymerase chain reaction. Heterologous bovine IVF showed no polyspermy, lower percentages of pronuclear formation, and a lower cleavage rate compared to homologous IVF group (34.8% vs. 89.3%). Heterologous murine IVF showed a lower cleavage rate than homologous IVF (9.6% vs. 77.1%). With respect to dolphin sperm chromatin, it was more stable, i.e. more resistant to EDTA-SDS decondensation than the bovine sperm chromatin. This study revealed the stability of the dolphin sperm chromatin and the ability of the dolphin spermatozoa to penetrate zona-intact bovine and murine oocytes, leading to hybrid embryo formation. PMID- 26149075 TI - A field study on artificial insemination of swamp and crossbred buffaloes with sexed semen from river buffaloes. AB - Sex preselection by flow sorting of X- and Y-sperm has been proven to be an efficient and economically feasible strategy for use in Holstein dairy cow breeding, and previous reports have demonstrated the feasibility of altering the sex ratio in buffalo species by using sexed semen in either artificial insemination or IVF. However, because buffalo reproductive physiology and farm management are different from Holsteins, factors involved in artificial insemination by sexed semen need to be further addressed before being applied in buffalo breeding at village-level husbandry. In this study, a total of 4521 swamp or crossbred (F1 or F2) buffaloes with natural estrus were inseminated with X sorted sperm from river buffaloes, resulting in a 48.5% (2194 of 4521) pregnancy rate and 87.6% (1895 of 2163) sex accuracy in the derived calves. The pregnancy rate obtained with sexed semen from Murrah bulls was higher than that of Nili Ravi, 52.5% (895 of 1706) versus 46.1% (1299 of 2815; P < 0.01), respectively. Also, significant variations were seen in pregnancy rates from inseminations performed in different seasons (P < 0.01) and by different technicians (P < 0.01). In contrast to Holsteins, no difference was seen in the pregnancy rate between heifers and parous buffalo cows, and buffalo cows with different genetic backgrounds (swamp type, crossbred F1 and F2) showed similar fertility after insemination with sexed semen. The findings in the present study under field conditions pave the way for application of sexing technology to buffalo breeding under village-level husbandry and diverse genetic backgrounds. PMID- 26149076 TI - Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions. AB - PURPOSE: The purpose of this study was to determine the association of AZFc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of DAZ and CDY1 gene copies with male infertility METHODS: Three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to AZFc subdeletion typing by STS PCR. Deletion of DAZ and CDY1 gene copies was done using sequence family variant analysis. Sperm concentration and motility were compared between men with and without AZFc subdeletions. Effect of the AZFc subdeletions on ICSI outcome was evaluated. RESULTS: Amongst the three AZFc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 %) and azoospermic (11.6 %) men as compared to controls (5.1 %). In men with AZFc subdeltions, loss of two DAZ and one CDY1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with OR of 29.7 and 26, respectively. These subdeletions had no effect on ICSI outcome, albeit there were an increased number of poor quality embryos in AZFc subdeleted group. CONCLUSION: AZFc subdeletions are a major risk factor for male infertility in the Indian population. In the subjects with AZFc subdeletions, the deletion of DAZ and CDY1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. Since these deletions can be vertically transmitted to the future male offspring by ICSI, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation. PMID- 26149079 TI - Correction: Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications. AB - Correction for 'Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications' by Xiangkui Ren et al., Chem. Soc. Rev., 2015, DOI: . PMID- 26149077 TI - Enhanced efficacy of photodynamic therapy by inhibiting ABCG2 in colon cancers. AB - BACKGROUND: Photodynamic therapy (PDT) contains a photosensitizing process, which includes cellular uptake of photosensitizer and delivery of light to the target. ATP-binding cassette subfamily G2 (ABCG2) regulates endogenous protoporphyrin levels. In human colon cancers, it is not fully examined the role of ABCG2 in porphyrin-based photodynamic therapy. METHODS: SW480 and HT29 cells were selected because they showed low and high ABCG2 expression levels, respectively. Pyropheophorbid-a (PPa) was used as a photosensitizer. Cells were exposed to a 670 nm diod laser. Cell viability and necrosi apoptosis was examined. Production level of singlet oxygen was detected with the photomultiplier-tube s/ -based singlet oxygen detection system. RESULTS: SW480 cells, which expressed lower level of ABCG2, showed the higher uptake of PPa than HT-29 cells. The uptake level of PPa was significantly correlated with the decreased cell viability after PDT. Pretreatment with a ABCG2 inhibitor, Ko-143, significantly enhanced the PDT efficacy in HT29 cells compared to vehicle-pretreated cells. To confirm the ABCG2 effect on PDT, we established ABCG2 over-expressing stable cells in SW480 cells (SW480/ABCG2). Furthermore, SW480/ABCG2 cells showed significantly decreased PDT effect compared to the control cells. The increased or decreased cell survival was significantly correlated with the production level of singlet oxygen after PDT. CONCLUSION: ABCG2 plays an important role in determining the PDT efficacy by controlling the photosensitizer efflux rate. This implies the control of ABCG2 expression may be a potential solution to enhance photosensitivity. PMID- 26149078 TI - Emergency pancreatic surgery--demanding and dangerous. AB - BACKGROUND: Elective pancreatic surgery can be carried out with mortality rates below 5% in specialized centers today. Only few data exist on pancreatic resections in emergency situations. The aim of the study was to characterize indications, procedures, and outcome of emergency pancreatic surgery in a tertiary center. METHODS: Prospectively collected data of all patients undergoing pancreatic operations at the authors' institution between October 2001 and December 2012 were analyzed regarding primary emergency operations in terms of indications, procedures, perioperative complications, and outcome. Emergency operations after preceding resections were excluded from the analysis. RESULTS: Twenty-three emergency operations were performed during the observation period. Indications were duodenal perforation (n = 8), upper GI bleeding (n = 6), complicated pseudocysts (n = 3), bile duct perforation (n = 2), pancreatic bleeding after blunt abdominal trauma (n = 1), pancreatic stent perforation (n = 1), necrotizing cholecystitis (n = 1), and ileus (n = 1). Procedures included partial and total duodeno-pancreatectomy (n = 15), cystojejunostomy (n = 2), distal pancreatectomy (n = 4), reconstruction of the ampulla Vateri (n = 1), and duodenectomy (n = 1). Median intraoperative blood loss was 750 (200-2500) ml and OP time 4.25 (1.75-9.25) h. Mean ICU stay was 21.3 (1-80) days with an overall surgical morbidity of 52.2%. Overall in-hospital mortality was 34.8% (8/23 pat.). CONCLUSIONS: Emergency pancreatic operations are infrequent and mainly performed due to duodenal perforation or bleeding; blunt abdominal trauma is rarely leading to emergency pancreas resections. They are associated with an increased morbidity and mortality and require a high level of surgical as well as interdisciplinary experience. Perioperative anesthesiological care and interventional radiological complication management are essential to improve outcome in this selective patient collective. PMID- 26149080 TI - Corrigendum: Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease. PMID- 26149081 TI - Removal of Anthracene and Fluoranthene by Waxy Corn, Long Bean and Okra in Lead Contaminated Soil. AB - The ability of waxy corn, long bean and okra to remove two polycyclic aromatic hydrocarbons (PAHs) from soil containing 0.63 mg Pb kg(-1) dry soil was assessed. The presence of Pb did not reduce the ability of these plants to remove the PAHs from soil. About 49 % of anthracene and 77 % of fluoranthene were removed from Pb spiked or non-spiked soil, respectively, after 30 days. Among the plants, okra was the most efficient at removing anthracene and fluoranthene in the presence or absence of Pb in soil after 30 days. Pb did not affect fluoranthene removal, but stimulated the removal of anthracene, by long bean, waxy corn and okra. However, growth of long bean and waxy corn was poor in Pb-spiked soil and waxy corn plants died around 22 days after transplantation. The results show some promise in using plants to remove PAHs from soil which is also co-contaminated with Pb. PMID- 26149082 TI - Plasmon enhanced visible light photocatalysis for TiO2 supported Pd nanoparticles. AB - A photocatalyst consisting of nanostructured Pd photochemically deposited on 20 nm TiO2 displays a reaction half-life for rhodamine b decolourisation of 0.5 minute compared to the 9.4 minutes for unmodified P25 under identical reaction conditions. We associate this increased decolourisation rate to the increase in solar light harvesting which we have measured at 8% due to a significant red shift in the absorption profile of the catalyst. We relate the increased absorption of light with a visible active plasmon effect that is associated with the Pd nanostructures on the TiO2. This overall red-shift in the light harvesting for the catalyst leads to photocatalytic activity for excitations up to 600 nm. PMID- 26149083 TI - Comparative effect of propolis of honey bee and some herbal extracts on Candida albicans. AB - OBJECTIVES: To determine the effect of propolis on Candida albicans and to compare it with the effects of some other herbal extracts and antibiotics on this pathogenic fungi. METHODS: The extracts of propolis, Thymus vulgaris, Caryophillium aromaticus, Echinophora platyloba, Allium cepa and Cinnamomum zeylanicum were prepared and the antifungi effects of the extracts were examined on Candida albicans ATCC10231 using disc-diffusion assay and micro-broth dilution. The minimum fungicidal concentration (MFC) and minimum inhibitory concentrations (MIC) as well as inhibition zone were evaluated and the anti fungi effects of herbal extracts were compared with amphotricin B and nystatin at the times of 24, 48 and 72 h. Data analysis was performed using t test. RESULTS: Obtained results showed that propolis extract with MIC90 and MFC equal to 39 and 65 MUg/mL, respectively, possess the highest antifungal activity when compared with other studied extracts. The extracts of Allium cepa and Thymus vulgaris, with MFC of 169 and 137 MUg/mL, respectively, showed the lowest effects on the fungi. Also nystatin and amphotricin B yielded better effects on the tested fungi compared with the effects of all studied extracts on Candida albicans. CONCLUSION: Propolis extract is effective in controlling Candida albicans. However, the issue requires further investigation on samples in animals and performing toxicological examinations. PMID- 26149084 TI - Borders and Modal Articulations. Semiotic Constructs of Sensemaking Processes Enabling a Fecund Dialogue Between Cultural Psychology and Clinical Psychology. AB - The notion of the border is an interesting advancement in research on the processes of meaning making within the cultural psychology. The development of this notion in semiotic key allows to handle with adequate complexity construction, transformation, stability and the breakup of the relationship between person/world/otherness. These semiotic implications have already been widely discussed and exposed by authors such Valsiner (2007, 2014), Neuman (2003, 2008), Simao (Culture & Psychology, 9, 449-459, 2003, Theory & Psychology, 15, 549-574, 2005, 2015), with respect to issues of identity/relatedness, inside/outside, stability/change in the irreversible flow of the time. In this work, after showing some of the basics of such semiotic notion of border, we discuss the processes of construction and transformation of borders through the modal articulation, defined as the contextual positioning that the person assumes with respect to the establishment of a boundary in terms of necessity, obligation, willingness, possibility, permission, ability. This modal subjective positioning acquires considerable interest from the clinical point of view since its degree of plasticity vs that of rigidity is the basis of processes of development or stiffening of relations between person/world/otherness. PMID- 26149085 TI - The Assessment of Distortion in Neurosurgical Image Overlay Projection. AB - BACKGROUND: Numerous studies have demonstrated the superiority of neuronavigation during neurosurgical procedures compared to non-neuronavigation-based procedures. Limitations to neuronavigation systems include the need for the surgeons to avert their gaze from the surgical field and the cost of the systems, especially for hospitals in developing countries. Overlay projection of imaging directly onto the patient allows localization of intracranial structures. A previous study using overlay projection demonstrated the accuracy of image coregistration for a lesion in the temporal region but did not assess image distortion when projecting onto other anatomical locations. Our aim is to quantify this distortion and establish which regions of the skull would be most suitable for overlay projection. METHODS: Using the difference in size of a square grid when projected onto an anatomically accurate model skull and a flat surface, from the same distance, we were able to calculate the degree of image distortion when projecting onto the skull from the anterior, posterior, superior, and lateral aspects. Measuring the size of a square when projected onto a flat surface from different distances allowed us to model change in lesion size when projecting a deep structure onto the skull surface. RESULTS: Using 2 mm as the upper limit for distortion, our results show that images can be accurately projected onto the majority (81.4%) of the surface of the skull. CONCLUSION: Our results support the use of image overlay projection in regions with <=2 mm distortion to assist with localization of intracranial lesions at a fraction of the cost of existing methods. PMID- 26149086 TI - DNA Methylation Analysis of HTR2A Regulatory Region in Leukocytes of Autistic Subjects. AB - Disturbed brain and peripheral serotonin homeostasis is often found in subjects with autism spectrum disorder (ASD). The role of the serotonin receptor 2A (HTR2A) in the regulation of central and peripheral serotonin homeostasis, as well as its altered expression in autistic subjects, have implicated the HTR2A gene as a major candidate for the serotonin disturbance seen in autism. Several studies, yielding so far inconclusive results, have attempted to associate autism with a functional SNP -1438 G/A (rs6311) in the HTR2A promoter region, while possible contribution of epigenetic mechanisms, such as DNA methylation, to HTR2A dysregulation in autism has not yet been investigated. In this study, we compared the mean DNA methylation within the regulatory region of the HTR2A gene between autistic and control subjects. DNA methylation was analysed in peripheral blood leukocytes using bisulfite conversion and sequencing of the HTR2A region containing rs6311 polymorphism. Autistic subjects of rs6311 AG genotype displayed higher mean methylation levels within the analysed region than the corresponding controls (P < 0.05), while there was no statistically significant difference for AA and GG carriers. Our study provides preliminary evidence for increased HTR2A promoter methylation in leukocytes of a portion of adult autistic subjects, indicating that epigenetic mechanisms might contribute to HTR2A dysregulation observed in individuals with ASD. PMID- 26149087 TI - Primary microRNA processing is functionally coupled to RNAP II transcription in vitro. AB - Previous studies in vivo reported that processing of primary microRNA (pri-miRNA) is coupled to transcription by RNA polymerase II (RNAP II) and can occur co transcriptionally. Here we have established a robust in vivo system in which pri miRNA is transcribed by RNAP II and processed to pre-miRNA in HeLa cell nuclear extracts. We show that both the kinetics and efficiency of pri-miRNA processing are dramatically enhanced in this system compared to that of the corresponding naked pri-miRNA. Moreover, this enhancement is general as it occurs with multiple pri-miRNAs. We also show that nascent pri-miRNA is efficiently processed before it is released from the DNA template. Together, our work directly demonstrates that transcription and pri-miRNA processing are functionally coupled and establishes the first in vivo model systems for this functional coupling and for co-transcriptional processing. PMID- 26149088 TI - Public knowledge and factors associated with inappropriate analgesic use: a survey in Thailand. AB - OBJECTIVE: This study aims to evaluate knowledge of analgesics and factors associated with inappropriate analgesic use among the public. METHODS: The cross sectional study was carried out in one large city in the south of Thailand. The survey was conducted using interview of people of age 16 or older. The questionnaire elicited information regarding knowledge, attitudes and behaviours on analgesic use including prevalence of taking paracetamol >4 g/day (overdosage) and not taking non-steroidal anti-inflammatory drugs (NSAIDs) with meals (inappropriate taking). KEY FINDINGS: Of 1982 participants, paracetamol overdose (n = 595) and inappropriate NSAID users (n = 751) were less likely to give correct answers about analgesics compared with appropriate users. The overdose use was inversely associated with knowledge on paracetamol (odds ratio (OR) 0.90; 95% confidence interval (CI), 0.83, 0.98) but directly associated with positive attitudes towards high dose taking (OR 2.15; 95% CI, 1.49, 3.11), and high frequency of analgesic use (OR 1.78; 95% CI, 1.24, 2.54). Inappropriate NSAID ingestion was inversely associated with knowledge on NSAIDs and directly associated with more commonly obtaining analgesics from community pharmacies (OR 0.87; 95% CI, 0.82, 0.92 and OR 1.27; 95% CI, 1.01, 1.61, respectively). CONCLUSIONS: Poor knowledge, positive attitudes towards high dose or high frequency of analgesic consumption and the patterns of using drugs were associated with inappropriate analgesic use especially that of paracetamol. PMID- 26149089 TI - Evaluation of the visit frequency and the use of questionnaires and indices for COPD: a national survey from the On-Sint study. AB - INTRODUCTION: Despite widespread recommendations to use standardized questionnaires and multidimensional indices for the assessment of patients with chronic obstructive pulmonary disease (COPD), few data are available on the application of these tools in clinical practice. This study evaluates the attitude of physicians participating in the On-Sint cohort toward the use of health status questionnaires and multidimensional indices, as well as toward the frequency of visits and spirometry in primary care and specialized care. METHODS: During the constitution of the On-Sint cohort, the participating physicians were surveyed about their clinical practice. They were questioned on the frequency of spirometry and visits and on the use of various questionnaires and indices. The health status questionnaires assessed were St. George's respiratory questionnaire, chronic respiratory questionnaire, airways questionnaire 20 and COPD assessment test (CAT). Physicians were also asked about the use of the medical research council (MRC) dyspnea scale and multidimensional indices such as body mass index, airflow obstruction, dyspnea, exercise capacity (BODE). RESULTS: Of the 356 physicians who participated in the study, 258 (72.5 %) completed the investigator's questionnaire (185 primary care, 73 specialized care). Nonscheduled visits were inversely proportional to the severity of COPD. Overall, 34.1% reported using health status questionnaires, mainly CAT (20.9%). We found differences between primary and specialized care in the use of multidimensional indices (84.9% vs 47.6%; P < 0.001). Of all the participants, 33.3% reported using the MRC scale and 28.7% the BODE index. CONCLUSIONS: Multidimensional indices and questionnaires are not commonly used with some differences between primary care and specialized care physicians. There is a considerable variability in the frequency of follow-up visits and spirometry. PMID- 26149090 TI - Short and long-term effects of hydraulic dredging on benthic communities and ocean quahog (Arctica islandica) populations. AB - The short and long-term effects of hydraulic dredging on ocean quahog (Arctica islandica) populations and on non-target organisms were examined in Pistilfjordur Bay, NE Iceland over a five-year period. The overall species richness was low and the fauna was composed of species typical of sandy seabeds characterised by frequent wave-induced disturbances. The initial effects of dredging on the overall benthic community were large. Most taxa were significantly affected by dredging, with abundances sometimes decreasing or increasing by more than 50% immediately after dredging. However, with the exception of the ocean quahog, their recovery was rapid, and most taxa attained similar abundances as in the undisturbed control sediments after three months, and all did so after about a year. The effects of dredging on ocean quahogs were drastic and long-lasting. Of the original ocean quahog biomass before fishing took place, the dredge captured 82%, while a further 11% was lost as a result of mortality due to shell damage and predation. The total direct and indirect loss of ocean quahog biomass within dredged tracks due to fishing was thus 93%. The recovery of ocean quahogs in fished areas was extremely slow. Five years after dredging, the total ocean quahog biomass in tracks had increased from 7% to 26% relative to that in the controls. The proportional increase among ocean quahogs of targeted sizes (>70 mm) was from 2% to 14% over the same period. This study shows that while the longer-term effects of hydraulic dredging on non-target benthic organisms were small, the effects of dredging on ocean quahog densities were drastic, with full recovery expected to take place on decadal time-scales. The impacts of dredging on ocean quahog populations at the scale of the fishery are discussed. PMID- 26149091 TI - Treating Psoriasis During Pregnancy: Safety and Efficacy of Treatments. AB - Psoriasis is a chronic inflammatory disease with a well-documented negative effect on the quality of life of affected patients. Psoriasis often occurs in the reproductive years, during which the issue of pregnancy needs to be addressed. The course of psoriasis during pregnancy is unpredictable, and many patients face the challenge of needing treatment during pregnancy. In this review we provide an overview of the key considerations for managing psoriasis in pregnant women, covering the potential effects of active psoriasis and co-morbid conditions on the health of the mother and fetus, as well as the effects of psoriasis treatment options on the developing fetus. Although there are no robust data on the safety of systemic treatment of pregnant women, increasing evidence regarding the safety of cyclosporine (ciclosporin) treatment as well as anti-tumor necrosis factor alpha is available and should be considered in pregnant women with moderate to severe psoriasis unresponsive to local corticosteroids and UVB light treatment. PMID- 26149092 TI - 23rd World Congress of Dermatology: Vancouver, Canada, June 8-13, 2015. PMID- 26149095 TI - Erratum to: Elucidating the neurophysiological underpinnings of autism spectrum disorder: new developments. PMID- 26149093 TI - Deficiency of CC chemokine ligand 2 and decay-accelerating factor causes retinal degeneration in mice. AB - CC chemokine ligand 2 (CCL2) recruits macrophages to reduce inflammatory responses. Decay-accelerating factor (DAF) is a membrane regulator of the classical and alternative pathways of complement activation. In view of the link between complement genes and retinal diseases, we evaluated the retinal phenotype of C57BL/6J mice and mice lacking Ccl2 and/or Daf1 at 12 months of age, using scanning laser ophthalmoscopic imaging, electroretinography (ERG), histology, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. In comparison to C57BL/6J mice, mutant mice had an increased number of autofluorescent foci, with the greatest number in the Ccl2(-/ )/Daf1(-/-) retina. ERG amplitudes in Ccl2(-/-)/Daf1(-/-), Ccl2(-/-) and Daf1(-/ ) mice were reduced, with the greatest reduction in Ccl2(-/-)/Daf1(-/-) mice. TUNEL-positive cells were not seen in C57BL/6J retina, but were prevalent in the outer and inner nuclear layers of Ccl2(-/-)Daf1(-/-) mice and were present at reduced density in Ccl2(-/-) or Daf1(-/-) mice. Cell loss was most pronounced in the outer and inner nuclear layers of Ccl2(-/-)/Daf1(-/-) mice. The levels of the endoplasmic reticulum chaperone GPR78 and transcription factor ATF4 were significantly increased in the Ccl2(-/-)/Daf1(-/-) retina. In comparison to the C57BL/6J retina, the phosphorylation of NF-kappaB p65, p38, ERK and JNK was significantly upregulated while SIRT1 was significantly downregulated in the Ccl2(-/-)/Daf1(-/-) retina. Our results suggest that loss of Ccl2 and Daf1 causes retinal neuronal death and degeneration which is related to increased endoplasmic reticulum stress, oxidative stress and inflammation. PMID- 26149094 TI - A conserved role of alphaA-crystallin in the development of the zebrafish embryonic lens. AB - alphaA- and alphaB-crystallins are small heat shock proteins that bind thermodynamically destabilized proteins thereby inhibiting their aggregation. Highly expressed in the mammalian lens, the alpha-crystallins have been postulated to play a critical role in the maintenance of lens optical properties by sequestering age-damaged proteins prone to aggregation as well as through a multitude of roles in lens epithelial cells. Here, we have examined the role of alpha-crystallins in the development of the vertebrate zebrafish lens. For this purpose, we have carried out morpholino-mediated knockdown of alphaA-, alphaBa- and alphaBb-crystallin and characterized the gross morphology of the lens. We observed lens abnormalities, including increased reflectance intensity, as a consequence of the interference with expression of these proteins. These abnormalities were less frequent in transgenic zebrafish embryos expressing rat alphaA-crystallin suggesting a specific role of alpha-crystallins in embryonic lens development. To extend and confirm these findings, we generated an alphaA crystallin knockout zebrafish line. A more consistent and severe lens phenotype was evident in maternal/zygotic alphaA-crystallin mutants compared to those observed by morpholino knockdown. The penetrance of the lens phenotype was reduced by transgenic expression of rat alphaA-crystallin and its severity was attenuated by maternal alphaA-crystallin expression. These findings demonstrate that the role of alpha-crystallins in lens development is conserved from mammals to zebrafish and set the stage for using the embryonic lens as a model system to test mechanistic aspects of alpha-crystallin chaperone activity and to develop strategies to fine-tune protein-protein interactions in aging and cataracts. PMID- 26149096 TI - Who left the PETs out?--Who?--Who? PMID- 26149097 TI - Pushing the limits or the new normal? Transcatheter aortic valve replacement in nonagenarians. PMID- 26149098 TI - Left upper lobectomy after coronary artery bypass grafting. AB - OBJECTIVE: Left upper pulmonary lobectomy or segmentectomy after coronary artery bypass grafting (CABG) risks injury to the grafts. We reviewed our experience. METHODS: This is a retrospective review of a prospective database from 1 surgeon, of patients who underwent left upper lobectomy after having previous CABG. RESULTS: Between June 1998 and June 2014, a total of 2207 patients underwent lobectomy by 1 surgeon; 458 (21%) had a left upper lobectomy, and 28 (6.1%) had had a previous CABG. Twenty-seven patients (96.4%) had a left internal mammary artery (LIMA) used for the bypass. Twenty-six patients (96.2%) had significant adhesions between their lung and the bypass grafts. Of patients who had a LIMA graft, 25 (92.6%) had the left upper lobe completely dissected free from their grafts, whereas 2 patients (7.1%) had a sliver of their lung left on the grafts. No patient had a postoperative myocardial infarction, and 30-day and 90-day survival rates were both 100%. All patients had a curative resection, and all had complete thoracic lymphadenectomy. CONCLUSIONS: Left upper lobectomy after CABG, in patients with previous CABG and LIMA grafting, is safe. Usually the entire lung can be safely mobilized off the bypass grafts; if needed, a small sliver of lung can be left on the grafts. A curative resection is possible with minimal perioperative cardiac morbidity, and excellent 30- and 90-day mortality. PMID- 26149099 TI - Measuring postoperative patient outcomes: Who knows best? PMID- 26149100 TI - Piggyback proximal anastomoses provide independent flow to target myocardium. PMID- 26149101 TI - Computational fluid dynamics: Solidifying fluid concepts in left ventricular assist device therapy. PMID- 26149102 TI - The aged and the ill: A decade of surgical aortic valve replacement outcomes. PMID- 26149103 TI - Comparison of two genetically distant type 2 porcine reproductive and respiratory syndrome virus (PRRSV) modified live vaccines against Vietnamese highly pathogenic PRRSV. AB - Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) known as pig high fever disease was first reported in China and has spread rapidly in neighboring southeastern Asian countries. The objective of this study was to evaluate the efficacy of a new type 2 PRRSV modified live vaccine (vaccine A) against a challenge with a HP-PRRSV and to compare the efficacy of two genetically distant type 2 PRRSV modified vaccines (vaccine A for lineage 8 and vaccine B for lineage 5) against HP-PRRSV (lineage 8) challenge. Pigs were divided into 4 groups (n=12/group); vaccinated challenged (2 groups), unvaccinated challenged, and unvaccinated unchallenged groups. Regardless of vaccines, vaccinated challenged pigs showed significantly lower (P<0.05) mean rectal temperatures and respiratory scores, levels of HP-PRRSV viremia, and lung lesions and HP-PRRSV antigens within lung lesions compared to unvaccinated challenged pigs. Vaccinated challenged pigs had significantly higher (P<0.05) numbers of interferon-gamma secreting cells (IFN-gamma-SC) compared to unvaccinated challenged pigs. Significant differences were also found when comparing two type 2 PRRSV vaccines after HP-PRRSV challenge. The use of type 2 PRRSV vaccine A was able to significantly reduce fever when compared to type 2 PRRSV vaccine B in vaccinated challenged pigs. Vaccination of pigs with vaccine A reduced viral loads in their blood and induced higher numbers of HP-PRRSV specific IFN-gamma-SC than vaccination of pigs with vaccine B. This study demonstrates partial protection of two genetically distant type 2 PRRSV vaccines against HP-PRRSV challenge in growing pigs. PMID- 26149104 TI - Decarboxylative alkynylation and carbonylative alkynylation of carboxylic acids enabled by visible-light photoredox catalysis. AB - Visible-light-induced photocatalytic decarboxylative alkynylations of carboxylic acids have been developed for the first time. The reaction features extremely mild conditions, broad substrate scope, and avoids additional oxidants. Importantly, a decarboxylative carbonylative alkynylation has also been carried out in the presence of carbon monoxide (CO) under photocatalytic conditions, which affords valuable ynones in high yields at room temperature. PMID- 26149105 TI - Hospitalist intervention for appropriate use of telemetry reduces length of stay and cost. AB - BACKGROUND: Telemetry monitoring is a widely used, labor-intensive, and often limited resource. Little is known of the effectiveness of methods to guide appropriate use. OBJECTIVE: Our intervention for appropriate use included: (1) a hospitalist-led, daily review of bed utilization, (2) hospitalist-driven education module for trainees, (3) quarterly feedback of telemetry usage, and (4) financial incentives. DESIGN/METHODS: Hospitalists were encouraged to discuss daily telemetry utilization on rounds. A module on appropriate telemetry usage was taught by hospitalists during the intervention period (January 2013-August 2013) on medicine wards. Pre- and post-evaluations measured changes regarding telemetry use. We compared hospital bed-use data between the baseline period (January 2012-December 2012), intervention period, and extension period (September 2014-March 2015). During the intervention period, hospital bed-use data were sent to the hospitalist group quarterly. Financial incentives were provided after a decrease in hospitalist telemetry utilization. SETTING: Stanford Hospital, a 444-bed, academic medical center in Stanford, California. RESULTS: Hospitalists saw reductions for both length of stay (LOS) (2.75 vs 2.13 days, P = 0.005) and total cost (22.5% reduction) for telemetry bed utilization in the intervention period. Nonhospitalists telemetry bed utilization remained unchanged. We saw significant improvements in trainee knowledge of the most cost saving action (P = 0.002) and the least cost-saving action (P = 0.003) in the pre and post-evaluation analyses. Results were sustained in the hospitalist group, with telemetry LOS of 1.93 days in the extension period. CONCLUSIONS: A multipronged, hospitalist-driven intervention to improve appropriate use of telemetry reduces LOS and cost, and increases knowledge of cost-saving actions among trainees. PMID- 26149106 TI - Unintended Consequences: The Story of PERF. PMID- 26149107 TI - The Role of Sleep in the Modulation of Gastroesophageal Reflux and Symptoms in NICU Neonates. AB - BACKGROUND: Newborns sleep about 80% of the time. Gastroesophageal reflux disease is prevalent in about 10% of neonatal intensive care unit infants. Concurrent polysomnography and pH-impedance studies clarify the relationship of gastroesophageal reflux with sleep. AIMS: To characterize spatiotemporal and chemical characteristics of impedance-positive gastroesophageal reflux and define symptom associations in sleep and wake states in symptomatic neonates. We hypothesized that frequency of impedance-positive gastroesophageal reflux events and their association with cardiorespiratory symptoms is greater during sleep. METHODS: Eighteen neonates underwent concurrent polysomnography with a pH impedance study. Impedance-positive gastroesophageal reflux events (weakly acidic or acidic) were categorized between sleep versus wake states: Symptom Index = number of symptoms with gastroesophageal reflux/total symptoms*100; Symptom Sensitivity Index = number of gastroesophageal reflux with symptoms/total gastroesophageal reflux*100; Symptom Association Probability = [(1 - probability of observed association between reflux and symptoms)*100]). RESULTS: We analyzed 317 gastroesophageal reflux events during 116 hours of polysomnography. During wake versus sleep, respectively, the median (interquartile range) frequency of impedance-positive gastroesophageal reflux was 4.9 (3.1-5.8) versus 1.4 (0.7-1.7) events/hour (P < 0.001) and the proximal migration was 2.6 (0.8-3.3) versus 0.2 (0.0-0.9) events/hour (P < 0.001). The Symptom Index for cardiorespiratory symptoms for impedance-positive events was 22.5 (0-55.3) versus 6.1 (0-13), P = 0.04, whereas the Symptom Sensitivity Index was 9.1 (0-23.1) versus 18.4 (0-50), P = 0.04, although Symptom Association Probability was similar (P = 0.68). CONCLUSIONS: Contrary to our hypothesis, frequency of gastroesophageal reflux in sleep is lower; however, spatiotemporal and chemical characteristics of gastroesophageal reflux and symptom-generation mechanisms are distinct. For cardiorespiratory symptoms during sleep, a lower Symptom Index entails evaluation for etiologies other than gastroesophageal reflux disease, a higher Symptom Sensitivity Index implies heightened esophageal sensitivity, and similar Symptom Association Probability indicates other mechanistic possibilities. PMID- 26149108 TI - Aggregation of Individual Sensing Units for Signal Accumulation: Conversion of Liquid-Phase Colorimetric Assay into Enhanced Surface-Tethered Electrochemical Analysis. AB - A novel concept is proposed for converting liquid-phase colorimetric assay into enhanced surface-tethered electrochemical analysis, which is based on the analyte induced formation of a network architecture of metal nanoparticles (MNs). In a proof-of-concept trial, thymine-functionalized silver nanoparticle (Ag-T) is designed as the sensing unit for Hg(2+) determination. Through a specific T Hg(2+)-T coordination, the validation system based on functionalized sensing units not only can perform well in a colorimetric Hg(2+) assay, but also can be developed into a more sensitive and stable electrochemical Hg(2+) sensor. In electrochemical analysis, the simple principle of analyte-induced aggregation of MNs can be used as a dual signal amplification strategy for significantly improving the detection sensitivity. More importantly, those numerous and diverse colorimetric assays that rely on the target-induced aggregation of MNs can be augmented to satisfy the ambitious demands of sensitive analysis by converting them into electrochemical assays via this approach. PMID- 26149109 TI - Atmospheric pressure chemical ionization of explosives using alternating current corona discharge ion source. AB - The high-sensitive detection of explosives is of great importance for social security and safety. In this work, the ion source for atmospheric pressure chemical ionization/mass spectrometry using alternating current corona discharge was newly designed for the analysis of explosives. An electromolded fine capillary with 115 um inner diameter and 12 mm long was used for the inlet of the mass spectrometer. The flow rate of air through this capillary was 41 ml/min. Stable corona discharge could be maintained with the position of the discharge needle tip as close as 1 mm to the inlet capillary without causing the arc discharge. Explosives dissolved in 0.5 ul methanol were injected to the ion source. The limits of detection for five explosives with 50 pg or lower were achieved. In the ion/molecule reactions of trinitrotoluene (TNT), the discharge products of NOx (-) (x = 2,3), O3 and HNO3 originating from plasma-excited air were suggested to contribute to the formation of [TNT - H](-) (m/z 226), [TNT - NO](-) (m/z 197) and [TNT - NO + HNO3 ](-) (m/z 260), respectively. Formation processes of these ions were traced by density functional theory calculations. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26149110 TI - Characterization of ice-nucleating bacteria using on-line electron impact ionization aerosol mass spectrometry. AB - The mass spectral signatures of airborne bacteria were measured and analyzed in cloud simulation experiments at the AIDA (Aerosol Interaction and Dynamics in the Atmosphere) facility. Suspensions of cultured cells in pure water were sprayed into the aerosol and cloud chambers forming an aerosol which consisted of intact cells, cell fragments and residual particles from the agar medium in which the bacteria were cultured. The aerosol particles were analyzed with a high resolution time-of-flight aerosol mass spectrometer equipped with a newly developed PM2.5 aerodynamic lens. Positive matrix factorization (PMF) using the multilinear engine (ME-2) source apportionment was applied to deconvolve the bacteria and agar mass spectral signatures. The bacteria mass fraction contributed between 75 and 95% depending on the aerosol generation, with the remaining mass attributed to agar. We present mass spectra of Pseudomonas syringae and Pseudomonas fluorescens bacteria typical for ice-nucleation active bacteria in the atmosphere to facilitate the distinction of airborne bacteria from other constituents in ambient aerosol, e.g. by PMF/ME-2 source apportionment analyses. Nitrogen-containing ions were the most salient feature of the bacteria mass spectra, and a combination of C4 H8 N(+) (m/z 70) and C5 H12 N(+) (m/z 86) may be used as marker ions. PMID- 26149111 TI - Isoflavones present in soybean seeds can be glycosylated at 4'-O position as indicated by the ratio of [Y0 -H](-) and [Y0 ](-) fragment ions. PMID- 26149112 TI - In situ analysis of soybeans and nuts by probe electrospray ionization mass spectrometry. AB - The probe electrospray ionization (PESI) is an ESI-based ionization technique that generates electrospray from the tip of a solid metal needle. In the present work, we describe the PESI mass spectra obtained by in situ measurement of soybeans and several nuts (peanuts, walnuts, cashew nuts, macadamia nuts and almonds) using different solid needles as sampling probes. It was found that PESI MS is a valuable approach for in situ lipid analysis of these seeds. The phospholipid and triacylglycerol PESI spectra of different nuts and soybean were compared by principal component analysis (PCA). PCA shows significant differences among the data of each family of seeds. Methanolic extracts of nuts and soybean were exposed to air and sunlight for several days. PESI mass spectra were recorded before and after the treatment. Along the aging of the oil (rancidification), the formation of oxidated species with variable number of hydroperoxide groups could be observed in the PESI spectra. The relative intensity of oxidated triacylglycerols signals increased with days of exposition. Monitoring sensitivity of PESI-MS was high. This method provides a fast, simple and sensitive technique for the analysis (detection and characterization) of lipids in seed tissue and degree of oxidation of the oil samples. PMID- 26149113 TI - Quantitation of ortho-cresyl phosphate adducts to butyrylcholinesterase in human serum by immunomagnetic-UHPLC-MS/MS. AB - Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2 benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to form the aged adduct ortho-cresyl phosphoserine (oCP-BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic-UHPLC-MS/MS method for the quantitation of unadducted BChE and the long-term CBDP biomarker, oCP-BChE, in human serum. The method has a reportable range from 2.0 ng/ml to 150 ng/ml, which is consistent with the sensitivity of methods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (>=85%) and precision (RSD <= 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP-BChE adduct was stable for at least 72 h at 4, 22 and 37 degrees C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20 and demonstrates a threefold improvement in sensitivity. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26149114 TI - Evaluation of the alpha-phenylvinyl cation as a chemical ionization reagent for the differentiation of isomeric substituted phenols in an ITMS. AB - Ion-molecule reactions between the alpha-phenylvinyl cation and isomeric naturally occurring phenols were investigated using a quadruple ion trap mass spectrometer. The alpha-phenylvinyl cation m/z 103, generated by chemical ionization from phenylacetylene, reacts with neutral aromatic compounds to form the characteristic species: [M + 103](+) adduct ions and the trans-vinylating product ions [M + 25](+) , which correspond to [M + 103](+) adduct after the loss of benzene. Isomeric differentiation of several ring-substituted phenols was achieved by using collision-induced dissociation of the [M + 103](+) adduct ions. This method also showed to be effective in the differentiation of 4-ethylguaiacol from one of its structural isomers that displays identical EI and EI/MS/MS spectra. The effects of gas-phase alkylation with phenylvinyl cation on the dissociation behavior were examined using mass spectrometry(n) and labeled derivatives. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26149118 TI - Sensitive electrochemical detection of vaccinia virus in a solution containing a high concentration of L-ascorbic acid. AB - Washing processes cannot fully remove interfering species that remain on biosensing surfaces when a sample solution contains a high concentration of interfering species. This study reports an immunosensing scheme employing electroreduction-based electrochemical-chemical (EC) redox cycling that allows sensitive detection of vaccinia virus (VV) in a solution containing a high concentration of L-ascorbic acid (AA). To obtain high signal amplification, an enzymatic reaction by beta-D-galactosidase (Gal) is combined with electroreduction-based EC redox cycling by an oxidant. Among the four possible oxidants (KIO3, NaClO, Ag2O, and H2O2), KIO3 shows the highest signal-to background ratio and is chosen. During an incubation period of 10 min, Gal converts beta-D-galactopyranoside into p-aminophenol (AP), which is oxidized to p quinone imine (QI) by KIO3. When -0.05 V vs. Ag/AgCl is applied to an immunosensing electrode, QI is reduced to AP, and the regenerated AP is then reoxidized by KIO3. The electroreduction-based EC redox cycling is induced. An indium-tin oxide electrode modified with reduced graphene oxide and an applied potential of -0.05 V are used to achieve low and reproducible background currents, slow O2 reduction, and fast electroreduction of QI. KIO3 favorably converts AA into noninterfering species during the incubation period. The detection limit for VV in commercial 50% mandarin juice (AA concentration = 0.7 mM) is 4 * 10(3) plaque-forming unit (PFU) per mL. The new EC redox cycling scheme is promising for sensitive detection of proteins, viruses, and bacteria in solutions containing high concentrations of AA. PMID- 26149115 TI - High-speed MALDI MS/MS imaging mass spectrometry using continuous raster sampling. AB - A matrix-assisted laser desorption/ionization time of flight/time of flight tandem mass spectrometer (MALDI TOF/TOF) has been used for high-speed precursor/fragment ion transition image acquisition. High-throughput analysis is facilitated by an Nd:YLF solid state laser capable of pulse repetition rates up to 5 kHz, a high digitizer acquisition rate (up to 50 pixels/s), and continuous laser raster sampling. MS/MS experiments are enabled through the use of a precision timed ion selector, second source acceleration, and a dedicated collision cell. Continuous raster sampling is shown here to facilitate rapid MS/MS ion image acquisition from thin tissue sections for the drug rifampicin and for a common kidney lipid, SM4s(d18:1/24:1). The ability to confirm the structural identity of an analyte as part of the MS/MS imaging experiment is an essential part of the analysis. Additionally, the increase in sensitivity and specificity afforded by an MS/MS approach is highly advantageous, especially when interrogating complex chemical environments such as those in biological tissues. Herein, we report continuous laser raster sampling TOF/TOF imaging methodologies which demonstrate 8 to 14-fold increases in throughput compared with existing MS/MS instrumentation, an important advantage when imaging large areas on tissues. PMID- 26149119 TI - Pattern mixture models for the analysis of repeated attempt designs. AB - It is not uncommon in follow-up studies to make multiple attempts to collect a measurement after baseline. Recording whether these attempts are successful or not provides useful information for the purposes of assessing the missing at random (MAR) assumption and facilitating missing not at random (MNAR) modeling. This is because measurements from subjects who provide this data after multiple failed attempts may differ from those who provide the measurement after fewer attempts. This type of "continuum of resistance" to providing a measurement has hitherto been modeled in a selection model framework, where the outcome data is modeled jointly with the success or failure of the attempts given these outcomes. Here, we present a pattern mixture approach to model this type of data. We re analyze the repeated attempt data from a trial that was previously analyzed using a selection model approach. Our pattern mixture model is more flexible and is more transparent in terms of parameter identifiability than the models that have previously been used to model repeated attempt data and allows for sensitivity analysis. We conclude that our approach to modeling this type of data provides a fully viable alternative to the more established selection model. PMID- 26149120 TI - Vitamin D Deficiency in Uygurs and Kazaks Is Associated with Polymorphisms in CYP2R1 and DHCR7/NADSYN1 Genes. AB - BACKGROUND: Our study is aimed to 1) clarify the vitamin D status in Uygur and Kazak ethnic populations and 2) elucidate the relationship between 14 SNPs (in 5 vitamin D-related genes) and vitamin D deficiency in these 2 ethnic populations. MATERIAL AND METHODS: A multistage-cluster sampling survey was carried out for residents with Uygur or Kazak ethnicity in Xinjiang, China. Anthropometric measurements were taken and the concentrations of 25OHD were measured. Fourteen common variants in VDR, GC, CYP2R1, CYP27B1, and DHCR7/NADSYN1 were genotyped by using multiple SNaPshot assay. Logistic regression analysis was performed to identify the possible risk factors for vitamin D deficiency, after adjusting for several environmental and biological factors. The pattern of SNP associations was distinct between Uygurs and Kazaks. RESULTS: Anthropometric measurements and the concentrations of 25OHD were obtained from 1873 participants (945 Uygur ethnic and 928 Kazak ethnic). The genotypes of 14 SNPs were measured for 300 Uygurs and 300 Kazaks. The median 25OHD concentration was as low as 10.4 ng/ml in Uygurs and 16.2 ng/ml in Kazaks. In Uygurs, the prevalence of vitamin D deficiency, in sufficiency, and sufficiency was 91.2%, 5.8%, and 3.0%, respectively. CYP2R1 rs10766197 was significantly associated with the presence of vitamin D deficiency in the Uygur ethnic population (P=0.019, OR=6.533, 95%C.I.: 361-31.357), while DHCR7/NADSYN1-rs12785878 was significantly associated with the presence of vitamin D deficiency in the Kazak ethnic population (P=0.011, OR=2.442, 95%C.I.: 1.224-4.873). Of 10 SNPs in VDR and GC genes, none was associated with vitamin D status in these 2 ethnic populations. CONCLUSIONS: Vitamin D insufficiency is highly prevalent in Uygurs and Kazaks living in Xinjiang, China. Polymorphisms in CYP2R1-rs10766197 and DHCR7/NADSYN1-rs12785878 are associated with vitamin D deficiency in Uygur and Kazak ethnic populations. PMID- 26149121 TI - Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. AB - Ergothioneine is a histidine thio-derivative isolated in 1909. In ergothioneine biosynthesis, the combination of a mononuclear non-heme iron enzyme catalyzed oxidative C-S bond formation reaction and a PLP-mediated C-S lyase (EgtE) reaction results in a net sulfur transfer from cysteine to histidine side-chain. This demonstrates a new sulfur transfer strategy in the biosynthesis of sulfur containing natural products. Due to difficulties associated with the overexpression of Mycobacterium smegmatis EgtE protein, the proposed EgtE functionality remained to be verified biochemically. In this study, we have successfully overexpressed and purified M. smegmatis EgtE enzyme and evaluated its activities under different in vitro conditions: C-S lyase reaction using either thioether or sulfoxide as a substrate in the presence or absence of reductants. Results from our biochemical characterizations support the assignment of sulfoxide 4 as the native EgtE substrate and the involvement of a sulfenic acid intermediate in the ergothioneine C-S lyase reaction. PMID- 26149123 TI - Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. AB - Our understanding of the key phosphorylation-dependent signalling pathways in the human malaria parasite, Plasmodium falciparum, remains rudimentary. Here we address this issue for the essential cGMP-dependent protein kinase, PfPKG. By employing chemical and genetic tools in combination with quantitative global phosphoproteomics, we identify the phosphorylation sites on 69 proteins that are direct or indirect cellular targets for PfPKG. These PfPKG targets include proteins involved in cell signalling, proteolysis, gene regulation, protein export and ion and protein transport, indicating that cGMP/PfPKG acts as a signalling hub that plays a central role in a number of core parasite processes. We also show that PfPKG activity is required for parasite invasion. This correlates with the finding that the calcium-dependent protein kinase, PfCDPK1, is phosphorylated by PfPKG, as are components of the actomyosin complex, providing mechanistic insight into the essential role of PfPKG in parasite egress and invasion. PMID- 26149124 TI - Prevalence of metabolic syndrome in a cohort of systemic lupus erythematosus patients from Northeastern Brazil: association with disease activity, nephritis, smoking, and age. AB - Systemic lupus erythematosus (SLE), an autoimmune inflammatory disease, is associated with an increased prevalence of accelerated atherosclerosis and cardiovascular events. Metabolic syndrome (MetS) is a set of cardiovascular risk factors in SLE patients, which may lead to a proinflammatory condition and increased morbidity and mortality. The objective of this study was to evaluate the prevalence of MetS in a cohort of SLE patients versus healthy controls, and to analyze the association of clinical and demographic factors. SLE patients (n = 146) treated at a Northeast Brazilian university hospital were evaluated with regard to demographic, clinical, laboratory, and anthropometric parameters and compared to controls (n = 101). MetS was diagnosed according to the definition of 2005 NCEP/ATP III. The average age of SLE patients was 41.7 +/- 12.5 years, and 91.8 % were female. MetS was significantly more prevalent in SLE patients (45.2 %) than in controls (32.7 %; p = 0.04). The MetS components such as hypertension, diabetes, and hypertriglyceridemia were significantly more prevalent in SLE. In the univariate analysis, MetS in SLE patients was associated with age, disease duration, Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index, smoking, menopause, nephritis, cyclophosphamide use, prednisone dose, and chloroquine use, which appeared to have a protective effect. In the logistic regression analysis, age, disease activity, nephritis, and smoking were statistically significant. The prevalence of MetS observed in our cohort of SLE patients from Northeastern Brazil is higher than controls. MetS components should be routinely investigated to minimize the occurrence of MetS and associated cardiovascular morbidity and mortality. PMID- 26149122 TI - Hepatitis B and C virus infection and risk of lymphoid malignancies: A population based cohort study (JPHC Study). AB - BACKGROUND: Several studies have assessed the association between hepatitis B virus (HBV) and hepatitis C virus (HCV) and non-Hodgkin's lymphoma. However, few studies are cohort by design, conducted within the Asian context and even fewer studies consider other lymphoid malignancies. The aim of this study was to assess the association between HBV and HCV and the risk of lymphoid malignancies among Japanese adults. MATERIALS AND METHODS: The Japan Public Health Center prospective-based Study Cohort II was initiated in 1993/1994. 20,360 subjects with available data on HBV and HCV infection status from blood samples were followed up until the end of 2010 for an average of 16 years. During 324,139 person-years, 120 newly diagnosed cases of lymphoid malignancies were identified. Cox proportional hazards models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95%CIs). RESULTS: Of 20,360 subjects, 508 were HBsAg positive, 11,035 were anti-HBc positive, and 1,129 subjects were anti-HCV positive at baseline. The presence of HBsAg was positively associated with malignant lymphoma, especially with non-Hodgkin's lymphoma (HR=3.56, 95%CI=1.37 9.18) and diffuse large B-cell lymphoma (HR=7.22, 95%CI=2.34-22.29). In contrast, no clear association was observed between the presence of anti-HBc and anti-HCV. CONCLUSION: In conclusion, HBsAg but not anti-HBc or anti-HCV was positively associated with malignant lymphoma, particularly non-Hodgkin's lymphoma and diffuse large B-cell lymphoma in Japanese adults. PMID- 26149125 TI - Meniscal extrusion or subchondral damage characterize incident accelerated osteoarthritis: Data from the Osteoarthritis Initiative. AB - Knee osteoarthritis (KOA) is typically a slowly progressive disorder; however, a subset of knees progress with dramatic rapidity. We aimed to describe magnetic resonance imaging (MRI) findings that are associated with accelerated KOA. We conducted a longitudinal descriptive study in the Osteoarthritis Initiative cohort. We selected participants who had no radiographic KOA at baseline with one of the following in the most severe knee: (1) accelerated KOA (progressed to end stage KOA within 48 months), (2) common KOA, and (3) no KOA at all visits. We enriched the sample by selecting knees with a self-reported or suspected knee injury. A musculoskeletal radiologist blinded to group assignments but not to time sequence performed MRI readings for the visit before and after an injury. We assessed 38 participants (knees), 66% were female, mean age 61 (9) years, and mean body mass index 28.5 (4.9) kg/m(2). Fifteen of 20 knees with no or common KOA, had no incident findings consistent with acute damage. Among the 18 knees with accelerated KOA most had incident findings: 13 (72%) had incident medial meniscal pathology with extrusion and 5 (28%) knees had subchondral damage. Incident MRI findings that are associated with incident accelerated KOA are characterized by structural damage that compromises subchondral bone or the function of the meniscus. Recognizing meniscal extrusion and/or change in shape, lateral meniscal tear, or acute subchondral damage may be vital for identifying individuals at risk for accelerated KOA. PMID- 26149126 TI - Characterization of the arsenite oxidizer Aliihoeflea sp. strain 2WW and its potential application in the removal of arsenic from groundwater in combination with Pf-ferritin. AB - A heterotrophic arsenite-oxidizing bacterium, strain 2WW, was isolated from a biofilter treating arsenic-rich groundwater. Comparative analysis of 16S rRNA gene sequences showed that it was closely related (98.7 %) to the alphaproteobacterium Aliihoeflea aesturari strain N8(T). However, it was physiologically different by its ability to grow at relatively low substrate concentrations, low temperatures and by its ability to oxidize arsenite. Here we describe the physiological features of strain 2WW and compare these to its most closely related relative, A. aestuari strain N8(T). In addition, we tested its efficiency to remove arsenic from groundwater in combination with Pf-ferritin. Strain 2WW oxidized arsenite to arsenate between pH 5.0 and 8.0, and from 4 to 30 degrees C. When the strain was used in combination with a Pf-ferritin-based material for arsenic removal from natural groundwater, the removal efficiency was significantly higher (73 %) than for Pf-ferritin alone (64 %). These results showed that arsenite oxidation by strain 2WW combined with Pf-ferritin-based material has a potential in arsenic removal from contaminated groundwater. PMID- 26149127 TI - Bacterial reference genes for gene expression studies by RT-qPCR: survey and analysis. AB - The appropriate choice of reference genes is essential for accurate normalization of gene expression data obtained by the method of reverse transcription quantitative real-time PCR (RT-qPCR). In 2009, a guideline called the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) highlighted the importance of the selection and validation of more than one suitable reference gene for obtaining reliable RT-qPCR results. Herein, we searched the recent literature in order to identify the bacterial reference genes that have been most commonly validated in gene expression studies by RT-qPCR (in the first 5 years following publication of the MIQE guidelines). Through a combination of different search parameters with the text mining tool MedlineRanker, we identified 145 unique bacterial genes that were recently tested as candidate reference genes. Of these, 45 genes were experimentally validated and, in most of the cases, their expression stabilities were verified using the software tools geNorm and NormFinder. It is noteworthy that only 10 of these reference genes had been validated in two or more of the studies evaluated. An enrichment analysis using Gene Ontology classifications demonstrated that genes belonging to the functional categories of DNA Replication (GO: 0006260) and Transcription (GO: 0006351) rendered a proportionally higher number of validated reference genes. Three genes in the former functional class were also among the top five most stable genes identified through an analysis of gene expression data obtained from the Pathosystems Resource Integration Center. These results may provide a guideline for the initial selection of candidate reference genes for RT qPCR studies in several different bacterial species. PMID- 26149128 TI - Neisseria meningitidis causes cell cycle arrest of human brain microvascular endothelial cells at S phase via p21 and cyclin G2. AB - Microbial pathogens have developed several mechanisms to modulate and interfere with host cell cycle progression. In this study, we analysed the effect of the human pathogen Neisseria meningitidis on cell cycle in a brain endothelial cell line as well as in primary brain endothelial cells. We found that N. Meningitidis causes an accumulation of cells in the S phase early at 3 and at 24 h post-infection that was paralleled by a decrease of cells in G2/M phase. Importantly, the outer membrane proteins of the colony opacity-associated (Opa) protein family as well as the Opc protein proved to trigger the accumulation of cells in the S phase. A focused cell cycle reverse transcription quantitative polymerase chain reaction-based array and integrated network analysis revealed changes in the abundance of several cell cycle regulatory mRNAs, including the cell cycle inhibitors p21(WAF1/CIP1) and cyclin G2. These alterations were reflected in changes in protein expression levels and/or relocalization in N. meningitidis-infected cells. Moreover, an increase in p21(WAF1/CIP1) expression was found to be p53 independent. Genetic ablation of p21(WAF1/CIP1) and cyclin G2 abrogated N. meningitidis-induced S phase accumulation. Finally, by measuring the levels of the biomarker 8-hydroxydeoxyguanosine and phosphorylation of the histone variant H2AX, we provide evidence that N. meningitidis induces oxidative DNA damage in infected cells. PMID- 26149129 TI - Statin treatment alters serum n-3 to n-6 polyunsaturated fatty acids ratio in patients with dyslipidemia. AB - BACKGROUND: The effects of statins on serum n-3 to n-6 polyunsaturated fatty acids (PUFAs) levels have not been fully evaluated. We examined the effects of two types of statins (rosuvastatin and pitavastatin) on serum PUFAs levels and their ratios in patients with dyslipidemia. FINDINGS: A total of 46 patients who were not receiving lipid-lowering therapy were randomly assigned to receive either 2.5 mg/day of rosuvastatin or 2 mg/day of pitavastatin. Serum PUFAs levels were measured at baseline, at 4 weeks, and at 12 weeks. Rosuvastatin was used to treat 23 patients, and the remaining 23 patients were treated using pitavastatin. Serum docosahexaenoic acid (DHA) levels decreased significantly at 12 weeks in both groups (rosuvastatin: from 169.6 to 136.3 MUg/mL, p = 0.006; pitavastatin: from 188.6 to 153.9 MUg/mL, p = 0.03). However, serum levels of eicosapentaenoic acid (EPA) and arachidonic acid (AA) did not change. In addition, the EPA/AA ratio did not change, whereas the DHA/AA ratio decreased significantly at 12 weeks in both groups (rosuvastatin: from 0.99 to 0.80, p = 0.01; pitavastatin: from 1.14 to 0.91, p = 0.003). No adverse events were observed during the study period. CONCLUSIONS: In this small, open-label, pilot study, rosuvastatin and pitavastatin decreased serum DHA levels and the DHA/AA ratio in patients with dyslipidemia. PMID- 26149130 TI - Differential replication properties among H9N2 avian influenza viruses of Eurasian origin. AB - Avian influenza H9N2 viruses have become panzootic in Eurasia causing respiratory manifestations, great economic losses and occasionally being transmitted to humans. To evaluate the replication properties and compare the different virus quantification methods, four Eurasian H9N2 viruses from different geographical origins were propagated in embryonated chicken egg (ECE) and Madin-Darby canine kidney epithelial cell systems. The ECE-grown and cell culture-grown viruses were monitored for replication kinetics based on tissue culture infectious dose (TCID50), Hemagglutination (HA) test and quantitative real time RT-PCR (qRT-PCR). The cellular morphology was analyzed using immunofluorescence (IF) and cellular ELISA was used to screen the sensitivity of the viruses to amantadine. The Eurasian wild type-H9N2 virus produced lower titers compared to the three G1-H9N2 viruses at respective time points. Detectable titers were observed earliest at 16 h post inoculation (hpi), significant morphological changes on cells were first observed at 32 hpi. Few nucleotide and amino acid substitutions were noticed in the HA, NA and NS gene sequences but none of them are related to the known conserved region that can alter pathogenesis or virulence following a single passage in cell culture. All studied H9N2 viruses were sensitive to amantadine. The G1-H9N2 viruses have higher replication capabilities compared to the European wild bird-H9N2 probably due to their specific genetic constitutions which is prerequisite for a successful vaccine candidate. Both the ECE and MDCK cell system allowed efficient replication but the ECE system is considered as the better cultivation system for H9N2 viruses in order to get maximum amounts of virus within a short time period. PMID- 26149131 TI - Dynamics of autochthonous soil viral communities parallels dynamics of host communities under nutrient stimulation. AB - Viruses are highly abundant in soils with their numbers exceeding those of cooccurring bacterial cells by 10- to over 1000-fold. Water and organic matter content influence the magnitude of the viral-to-bacterial ratio in soils; thus, ecosystem type and land use shape interactions between viral and host microbial communities in soils. Less understood are the shorter term interactions between viral and host communities that ultimately maintain the large viral standing stock within soils. This study examined short-term dynamics of viral and bacterial communities in soils to determine whether the growth of soil bacterial communities results in the production of soil viruses, and if viral community responses occur within specific populations. In microcosms amended with different carbon sources, increases in viral abundance (VA) accompanied increases in bacterial abundance (BA) and bacterial respiration rate (BRR). The timing and intensity of increases in BA, VA and BRR were different across C sources suggesting differences in the predominant mode of viral replication within growth stimulated bacterial populations. Moreover, compositional changes occurred in soil bacterial and viral communities indicating that new viral production arose from a subset of host populations. To our knowledge, these are the first observations of soil viral populations responding to short-term changes in soil bacterial communities. PMID- 26149132 TI - Functions of miR-9 and miR-9* during Aging in SAMP8 Mice and Their Possible Mechanisms. AB - OBJECTIVE: To explore the functions of miR-9 and miR-9(*) in SAMP8 mice during the aging and their possible mechanisms. METHODS: SAMP8 mice(4-,8-,12-month old,respectively)were selected,three age-matched SAMR1 mice were used as the control group with three mice in each group. The brains were collected and then sectioned for in situ hybridization of miR-9 and miR-9(*). Mimics or inhibitors of miR-9 and miR-9(*) were transfected into N2a cells,and the effects of overexpression or knockdown of the microRNAs on the cell cycle were detected by flow cytometry. Target genes were predicted by bioinformatic analysis and confirmed by dual luciferase assay. RESULTS: Expressions of miR-9 and miR-9(*) in hippocampus of SAMP8 mice were lower than those of SAMR1 mice. Knockdown of miR-9 and miR-9(*) induced a prolonged G1 phase and a shortened S phase in N2a cells;in contrast,miR-9 and miR-9(*) overexpression showed opposite effects. The predicted target genes of miR-9 were PSEN1,SCN2B,MAP3K3,and BACE1,and that of miR-9(*) was CDKn1c. Dual luciferase reporter gene assay showed that miR-9 targeted MAP3K3 while miR-9(*) targeted CDKn1c. CONCLUSION: miR-9 and miR-9(*) play an important role during aging via the target genes MAP3K3 and CDKn1c in the SAMP8 mice. PMID- 26149133 TI - Changes in the Expression of Glucose-regulated Protein 78 in the Occurrence and Progression of Pancreatic Cancer in Mouse Models. AB - OBJECTIVE: To investigate the changes in the expression of glucose-regulated protein 78 (GRP78) in the occurrence and progression of pancreatic cancer in mouse models. METHODS: The mouse models of chronic pancreatitis,pancreatic intraepithelial neoplasia (PanIN), and pancreatic cancer were successfully established by dimethyl benzene and anthracene (DMBA) embedding in situ. GRP78 expression was detected in various stages by immunohistochemistry. RESULTS: Of these 60 mouse models, 18 mice (30%) died during the observation period. Two months after the embedding,the survived mice were sacrificed,and HE staining and IHC staining were performed. Among these mice, 9 (15%) developed chronic pancreatitis; 18 (30%) had PanIN [PanIN1,5 (8.3%);P anIN2,9 (15%); and PanIN 3,4 (6.7%)];15 (25%) developed pancreatic cancer. Immunohistochemistry showed that the expression of GRP78 in pancreatic cancer tissue was significantly higher than that in adjacent noncancerous duct cells (chi(2)=13.39,P =0.000). Also, GRP78 expression in pancreatic cancer tissue and high grade PanIN was significantly higher than that in low grade PanIN and chronic pancreatitis (chi(2)=17.84,P=0.000). CONCLUSION: The expression of GRP78 remarkably differs in different stages of pancreatic cancer and therefore is associated with the occurrence and progression of this disease. PMID- 26149134 TI - In Vivo and In Vitro Inhibitory Effects of Icariin on Angiogenesis. AB - OBJECTIVE: To investigate the inhibitory effects of icariin(ICA),an active ingredient of Herb Epimedii,on angiogenesis. METHODS: The chick chorioallantoic membrane(CAM)assay was adopted to evaluate the effects of various doses of the ICA on the angiogenesis. The cell growth inhibitory effect of ICA on human umbilical vein endothelial cells(HUVEC)was measured by MTT assay. Cell cycle arrest and the induction of apoptosis were evaluated by flow cytometry. The effect of ICA on the migration of HUVEC cells was measured on Transwell model. RESULTS: ICA remarkably inhibited angiogenesis in CAM in a concentration dependent manner. The proliferation of HUVEC cells was inhibited by ICA, and the effect was time-and concentration-dependent. ICA-treated HUVEC cells showed cell cycle arrest;180 MUg/ml of ICA decreased the percentage of migrating HUVEC cells by 78.0%. CONCLUSION: ICA can effectively suppress angiogenesis;however,its in vivo inhibitory effect on angiogenesis warrants further investigations. PMID- 26149135 TI - Effects of Estrogen on Insulin Sensitivity and Adipokines in Mice. AB - OBJECTIVE: To study the potential mechanisms via which estrogen exerts its effects on the insulin sensitivity in mice. METHODS: Totally 36 female C57BL/6J mice aged 6 weeks were randomly divided into six groups:normal diet (NOR) group, normal diet with ovariectomy (NOR+OVX) group, normal diet with ovariectomy and estrogen replacement (NOR+OVX+E2) group,high-fat diet (HF) group, high-fat diet with ovariectomy (HF+OVX) group, and high-fat diet with ovariectomy and estrogen replacement (HF+OVX+E2) group. There were six mice in each group. After the ovariectomy based on the grouping, the mice were given normal diet or high-fat diet for 20 weeks. The intervention groups were given estrogen (5 MUg/d,subcutaneous injection) for 20 days. Then,the body weight,visceral fat weight,oral glucose tolerance and insulin sensitivity (by euglycemic hyperinsulinemic clamp test), and serum leptin, adiponectin,and resistin levels were compared among these six groups. RESULTS: Compared with HF group, the HF+OVX group had significantly higher body weight and visceral fat weight and lower glucose tolerance, which were significantly improved after estrogen replacement therapy (all P<0.05). However, these indicators showed no significant differences among groups with normal diets (all P>0.05). The insulin sensitivity of ovariectomized mice was significantly decreased in both high-fat and normal diet groups and was also improved significantly after estrogen replacement (P<0.05). The serum leptin was increased and adiponectin was decreased significantly in ovariectomized mice, and the improvements of these two adipokines were also statistically significant after estrogen therapy (P<0.05): however,the serum resistin level was not significantly different among these 6 groups (P>0.05). CONCLUSIONS: Estrogen replacement therapy can improve insulin resistance by lowering body weight. In addition, it can exert its effect directly on adipose tissue,improve the levels of adipokines,reduce the amount of visceral fat, and improve insulin sensitivity in mice. PMID- 26149136 TI - Association between KLKB1 Polymorphisms and Pulmonary Thromboembolism. AB - OBJECTIVE: To investigate the potential correlation between the single nucleotide polymorphisms (SNPs) in the KLKB1 region and pulmonary thromboembolism(PTE) in a Chinese Han population. METHODS: In this case-control study, 95 patients with confirmed PTE were enrolled as the PTE group and 90 healthy subjects as the control group. The genotypes, alleles, and haplotypes of the SNPs were analyzed with PLINK 1.07 and Haploview 4.2 software using chi-square test and Logistic regression analysis. SNPs were further analyzed under three genetic models (additive, dominant, and recessive). RESULTS: The distribution of rs3733402 in KLKB1 gene showed significant difference between PTE group and control group (P=0.041). The distributions of GTG haplotypes consisted of rs2292423, rs4253325,and rs3733402 in KLKB1 gene were also significantly different between PTE group and control group(P=0.040). CONCLUSION: The rs3733402 locus variation in KLKB1 gene is associated with PTE in Chinese Han people. PMID- 26149137 TI - Expressions of Tumor Necrosis Factor alpha-induced Protein 3 and Mammary Serine Protease Inhibitor in Radiotherapy of Nasopharyngeal Carcinoma. AB - OBJECTIVE: To study the expressions of tumor necrosis factor alpha-induced protein 3(TNFAIP3) and mammary serine protease inhibitor (Maspin) in the radiotherapy of nasopharyngeal carcinoma and explore the differences in radiosensitivity and radioresistance,the relation with the occurrence and development of radioresistance. METHODS: The TNFAIP3 and Maspin mRNA expressions were detected by using TNFAIP3 and Maspin multi-point labeled DIG probes in situ hybridization. RESULTS: In radiosensitivity and radioresistance of nasopharyngeal carcinoma,the moderately and strongly positive TNFAIP3 mRNA expression rates were 27.50% and 48.33% (P=0.037), and the moderately and strongly positive Maspin mRNA expression rates were 67.50% and 46.67% (P=0.040). In the radioresistance of nasopharyngeal carcinoma,TNFAIP3 mRNA moderately and strongly positive expressions were positively correlated with TNM stage (P=0.005). In distant metastasis and no distant metastasis (70.00% and 37.50%, P=0.018), the expression rates had statistical significance. The Maspin mRNA moderately and strongly positive expressions were positively correlated with TNM stage (P=0.039) and T stage (P=0.021). In distant metastasis and no distant metastasis (65.00% and 37.50%, P=0.044), the expression rates had statistical significance. CONCLUSION: TNFAIP3 may be involved in the development of radioresistant nasopharyngeal carcinoma,and Maspin may be related with the invasion and metastasis of radioresistant nasopharyngeal carcinoma. PMID- 26149138 TI - Effect of Crosslinks on the Stability of the Spine and the Pedicle Screw Fixation. AB - OBJECTIVE: To evaluate the effect of crosslinks on the stability of the spine and pedicle screws. METHODS: Compression fracture of the L1 vertebra was produced in 30 fresh thoracic and lumbar vertebrae samples obtained from adult sheep, which were divided into 3 groups (n=10)with lot-drawing method. Four screws were fixed onto the superior and inferior pedicles of vertebral arch close to the fractured vertebrae, with different number of crosslinks (0 in Group A,1 in Group B, and 2 in Group C) on the rods. After fixation, the samples were subject to 10 000 times of fatigue test with 1.5 Hz load on the HY-3080 computer-control electronic universal test machine and HY-1000NM computer-control torsion test machine. The axial compressive stiffness, maximum pullout strength,and range of motion (ROM) of 6 directions, i.e., flexion, extension, left and right lateral bending, and left and right axial rotation of the 3 groups were measured and compared. RESULTS: There were no statistically significant differences in axial compressive stiffness as well as the ROM of flexion, extension, and left and right lateral bending (all P>0.05). The maximum pullout strength was significantly smaller in Group A and Group B than in Group C [(129.56+/-29.63)N vs.(294.67+/-23.25) N,P=0.000;(254.02+/-36.29)vs.(294.67+/-23.25)N, P=0.006]. The ROM of left axial rotation was the highest in Group A(13.35 degrees +/-1.06 degrees ), followed by Group B(12.23 degrees +/-1.06 degrees )and Group C (11.04 degrees +/-0.74 degrees )(F=13.44, P=0.000; Group B vs. Group A, P=0.000; Group B vs. Group C, P=0.001; Group C vs. Group A,P=0.000). The ROM of right axial rotation was also the highest in Group A(13.56 degrees +/-1.15 degrees ), lower in Group B (12.39 degrees +/-1.01 degrees ) and the lowest in Group C (10.81 degrees +/-0.51 degrees ) (F=21.91, P=0.000; Group B vs. Group A,P=0.002; Group B vs. Group C, P=0.001; Group C vs. Group A, P=0.000). CONCLUSION: Crosslinks may reinforce the pullout strength of the screws and improve the axial stability of the spine. PMID- 26149139 TI - Clinical Value of Ultrasonography in Diagnosing Diffuse Thyroid Diseases Accompanied with Suspicious Nodules. AB - OBJECTIVE: To investigate the diagnostic value of ultrasonography for diffuse thyroid disease accompanied with suspicious nodules. METHODS: A total of 148 patients with diffuse thyroid diseases accompanied with suspicious nodules underwent both ultrasonography and ultrasound-guided biopsy, and the results were analyzed and compared. RESULTS: Among these 148 patients, 44 had Hashimoto's thyroiditis and 104 had Graves'disease. Totally 151 suspicious lesions were detected by ultrasonography, among which 48 lesions were pathologically confirmed to be benign and 103 malignant. Thirteen malignant lesions were diagnosed as benign by pre-operative ultrasonography, which were confirmed to be malignant after the surgical resection due to other suspected or confirmed malignant lesions. The detection rate of diffuse thyroid disease accompanied with thyroid cancer by per-operative ultrasound was 68.21%, and the misdiagnosis rate was 31.79%. The gender of patients(P=0.36), number of nodules(P=0.08), and blood flow types in lesions(P=0.080) had no significant difference between the benign and malignant groups, whereas internal echo(P=0.040), margin(P=0.000), shape(P=0.001), and calcification features(P=0.000)showed significant differences. Up to 80.74% of the lesions with hyperechoic calcification were malignant. CONCLUSIONS: Gray-scale sonographic features are helpful for the differential diagnosis of nodules in patients with diffuse thyroid diseases. Nodules in the isthmus and those accompanied with multiple nodules should be noticed. PMID- 26149140 TI - Performance of Ultrasonic Shear Wave Elastography in Assessing Benign and Malignant Breast Lesions. AB - OBJECTIVE: To determine the best shear wave elastography (SWE) quantitative parameters including the maximum elasticity (Emax), mean elasticity(Emean), minimum elasticity, standard deviation and ratio of Emean (Eratio) in assessing benign and malignant breast lesions. METHODS: Totally 302 breast lesions underwent conventional ultrasound and SWE. Each lesion was classified according to ultrasound Breast Imaging Reporting and Data System (BI-RADS). The receiver operating characteristic(ROC) curves were used to determine the cut-off values of SWE quantitative parameters and to suggest breast lesions as benign or malignant. The sensitivity,specificity and the Youden index (sum of sensitivity and specificity minus 1) of SWE quantitative parameters were compared,and then the sensitivity,specificity and the Youden index of the combinations of each SWE parameters in assessing breast lesions were compared. RESULTS: The sensitivity,specificity and the Youden index of the Emax were 0.87,0.97 and 0.84,which were higher than other SWE parameters (all P<0.01). The sensitivity, specificity and the Youden index of Emax combined with ultrasound BI-RADS were 0.86,0.97 and 0.83, which were higher than other combinations (all P<0.01). CONCLUSIONS: Compared with other parameters, Emax has the best performance in assessing breast lesions. It can be used as an important quantitative indicator for the evaluation of benign and malignant breast lesions. PMID- 26149141 TI - Value of Quantitative Three-dimensional Doppler Ultrasound in the Differentiation of Benign and Malignant Thyroid Nodules. AB - OBJECTIVE: To investigate the role of quantitative three-dimensional (3D) power Doppler ultrasound in differentiating malignant and benign thyroid nodule. METHODS: A total of 92 lesions in 86 patients were preoperatively examined using 3D power Doppler ultrasound. The Virtual Organ Computer-aided Analysis(VOCAL) imaging program was used to analyze the stored volume ultrasound. The differences in the mean gray value (MG), vascularization index (VI), flow index(FI), and vascularization flow index (VFI) were compared between benign and malignant lesions. RESULTS: The MG of the malignant thyroid nodules was significantly lower than that of the benign ones (28.27+/-7.21 vs. 32.89+/-8.73,P=0.007). The benign nodules had significantly higher VI,FI,and VFI than the malignant nodules [VI:(40.43+/-26.55)% vs. (26.87+/-23.06)%,P=0.011;FI:41.03+/-7.19 vs. 37.51+/ 7.17,P=0.022;VFI:18.23+/-14.60 vs. 11.47+/-12.47, P=0.009]. Also,76.5% (39/51) of the malignant nodules and 92.7% (38/41) of the benign nodules had higher VIs in the shell of the lesion than that of the whole lesion,and 80.4%(41/51) of the malignant nodules and 95.1% (39/41) of the benign nodules had higher FIs in the shell of the lesion than that of the whole lesion. CONCLUSIONS: Quantitative 3D power Doppler ultrasound provides a useful tool in distinguishing benign and malignant thyroid nodules. The malignant thyroid nodules have lower echoes than the benign nodules, wherese the benign nodules have larger blood flow than the malignant nodules. PMID- 26149142 TI - Discrepancy of Papillary Thyroid Carcinoma Sizes Measured by Ultrasonography and Pathology. AB - OBJECTIVE: To compare the size of papillary thyroid carcinoma on ultrasonography(US)and the actual size measured during histological examination and to discuss the potential causes of such discrepancy. METHODS: A total of 148 patients with histologically confirmed papillary thyroid carcinoma underwent thyroid surgery in our center from December 2012 to May 2013. Patients were stratified based on the size,morphology,margin,cystic component,and presence of Hashimoto's disease to compare the discrepancy of the US and pathalogical measurements. RESULTS: The mean sizes of the nodules measured by US and pathology were(1.58+/-0.94)cm and(1.33+/-0.84)cm,respectively(P=0.000). In 70.9%(105/148)of the nodules,the sizes measured by US were larger than those measured by pathology. In 17.6%(26/148)of the nodules,the sizes measured by US were smaller than those measured by pathology. In 1.1-1.4 cm size subgroup,the difference between mean ultrasound diameter and pathologic diameter was not significant [(1.21+/-0.11)cm vs.(1.11+/-0.32)cm,P=0.062]. In 0.1-1.0 cm size subgroup,the mean sizes of the nodules measured by US and pathology were(0.75+/-0.19)cm and(0.62+/-0.23)cm,respectively(P=0.000). In >=1.5 cm size subgroup,the mean sizes of the nodules measured by US and pathology were(2.48+/-0.70)cm and(2.03+/ 0.81)cm(P=0.000). CONCLUSIONS: There is a significant discrepancy between US and pathologic size measurements for papillary thyroid carcinoma. However,for nodules sized 1.1-1.4 cm,the ultrasound and pathologic measurements are more likely to be consistent. PMID- 26149143 TI - Sonographic and Pathologic Features of Struma Ovarii. AB - OBJECTIVE: To investigate the sonographic features of struma ovarii and its corresponding histopathologic findings. METHODS: The sonographic and histopathological features of 72 patients with histopathologically comfirmed struma ovarii who were treated in Peking Union Medical College Hospital from January 2005 to December 2014 were retrospectively reviewed. RESULTS: Of these 72 patients,71 had benign struma ovarii(73 lesions)and one patient had malignant struma ovarii(1 lesion). On ultrasonography,all the 73 benign lesions had distinct margin,45(61.6%)had multilocular cystic or cystic-solid mass,49(67.1%)had irregular shape,and 28(38.4%)had nodular solid protrusions in the cystic areas. On the color Doppler flow imaging,36(49.3%)lesions had blood flow signals. The ultrasonographic features of the malignant struma ovarii lesion were multilocular cystic-solid mass with several nodular solid protrusions in the cysic areas;on the color Doppler flow imaging,blood flow signals were visible within septa and solid areas. CONCLUSIONS: The sonographic features of struma ovarii are diverse. If ultrasonography reveals multilocular cystic or cystic solid mass with distinct margin and isoechoic or hyperechoic nodular solid protrusions in the cystic areas with visible blood flow signals,the diagnosis of struma ovarii should be considered. PMID- 26149144 TI - Relationship between Variation of Pre-ablation Stimulated Thyroglobulin and Distant Metastasis in Patients with Differentiated Thyroid Cancer. AB - OBJECTIVE: To investigate the relationship between the dynamic variation of pre ablation stimulated thyroglobulin(sTg)and distant metastasis in patietns with differentiated thyroid cancer(DTC). METHODS: DTC patients after total or near total thyroidectomy were divided into two groups as M1 group(n=38)and M0 group(n=130)according to the presence of distant metastases or not. Clinical data including pre-ablation sTg and the corresponding thyrotropin(TSH)values were dynamically measured. The pre-ablation sTg and corresponding TSH collected at the first time were defined as Tg1 and TSH1,while as Tg2 and TSH2 at the last time. chi(2) test was used to compare the variation tendency of sTg between these two groups. Tg1,Tg2,pre-ablation sTg variation(?Tg),and ?Tg/?TSH ratio between M0 and M1 were compared by Mann-Whitney rank-sum test. The receiver operating characteristic(ROC)curves and diagnostic critical point(DCP)were employed to evaluate the predictive values of the above indicators. RESULTS: Both Tg1 and Tg2 of M1 were significantly higher than those of M0(the Mann-Whitney rank-sum test:Tg1 P<0.001,Tg2 P<0.001). The corresponding areas under the ROC curve(AUC)to differentiate the two groups were 0.921 and 0.942,respectively. The cut-off value of Tg2,which was more accurate in predicting distant metastasis,was 24.3 ng/ml with a sensitivity of 92.11% and a specificity of 83.85%. Both ?Tg and ?Tg/?TSH between these two groups were significantly different(the Mann-Whitney rank-sum test:?Tg P=0.002,?Tg/?TSH P<0.001). ?Tg/?TSH worked better than Tg2 in predicting distant metastasis with both higher accuracy(87.50%)and higher specificity(86.92%). CONCLUSIONS: Dynamically tracing pre-ablation sTg may improve the accuracy and specificity of distant metastases prediction in DTC patients. ?Tg/?TSH,which means the ratio of sTg variation to TSH variation,may be a useful diagnostic marker for predicting distant metastases in DTC. PMID- 26149145 TI - Imaging Potential and Biodistribution in vivo of 2-[18F]Fluoropropionic Acid in Breast Cancer-bearing Mice. AB - OBJECTIVE: To investigate the imaging potential and biodistribution in vivo of a novel positron imaging agent,2-[(18)F]fluoropropionic,in breast cancer-bearing mice. Methods: 2-[(18)F]fluoropropionic acid (7.4-11.1 MBq)was injected into the breast cancer-bearing mice via tail vein,followed by micro positron emission tomography at 60 min and 120 min.The radioactivity per volume (Bq/ml) in organs was transferred to percentage injected dose per gram(% ID/g)by Inveon Research software and the biodistribution of 2-[(18)F]fluoropropionic acid in organs was deduce.The same operations were done with (18)F-FDG. RESULTS: 2 [(18)F]fluoropropionic acid was mainly distributed in the urinary bladder,intestine,and liver between 60 min to 120 min.The breast cancer at right flank was visualized clearly,and the radioactivity uptake was (13.74+/-1.97)% ID/g and (14.84+/-1.06)% ID/g,respectively,at these two time points (P=0.454).The radioactivity uptakes in muscle and brown tissue were relatively low.The radioactivity uptake of (18)F-FDG was (10.27+/-2.34)% ID/g at the breast cancer 60 min after injection,and radioactivity uptake of the brown fat on the back was obvious. CONCLUSIONS: Positron imaging agent 2-[(18)F]fluoropropionic acid can be used to image breast cancer.It may be applied in the noninvasive imaging of breast cancer in clinical settings. PMID- 26149146 TI - Comparison of Pain Thresholds and Analgesic Effects of Parecoxib Sodium in Surgical Patients of Different Racial and Religious Backgrounds. AB - OBJECTIVE: To explore the differences of the thresholds of pain and analgesic effects of parecoxib sodium among patients with different racial and religious backgrounds. METHODS: A total of 48 male patients aged 18 to 38 years who had undergone elective laparoscopic appendectomy under general anesthesia in our centers were enrolled in our study and then divided into 6 groups(n=8 in each group)based on their racial backgrounds(three levels:Mongoloid,Negroid,and Europoid)and religious backgrounds(two levels:without religion background,with religion background).All subjects received the same anesthesia,surgical procedure,and postoperative analgesia with parecoxib sodium. The temperature pain threshold and electrical pain threshold were detected 1h before and after analgesia. RESULTS: The threshold of pain was higher in Europoids than in Negroids and Mongoloids before and after treatment. The temperature pain threshold and electrical pain threshold were not significantly different between subjects with or without religious background(before analgesic therapy:F=251.119,P=0.130,F=275.861,P=0.059;after analgesic therapy:F=308.531,P=0.086,F=180.062,P=0.078). Also,there was no interaction between the racial and religious backgrous in terms of temperature pain threshold and electrical pain threshold(F=13.553,P=0.091,F=22.001,P= 0.089;after analgesic therapy:F=4.624,P=0.089,F=15.935,P=0.094). CONCLUSIONS: The threshold of pain differs among individuals with different racial background:it is highest in Europoids,followed by Negroids and Mongoloids. It shows no obvious difference in people with different religious backgrounds. PMID- 26149147 TI - Hemodynamic Changes in Patients Undergoing Pericardiectomy. AB - OBJECTIVE: To observe the hemodynamic changes in patients undergoing pericardiectomy at different operational stages. METHODS: Totally 16 consecutive patients receiving radical pericardiectomy were enrolled in this observational study. Hemodynamic variables were monitored continuously by pulse-indicated continuous cardiac output(PiCCO)system. Totally,three sets of intraoperative hemodynamic parameters were obtained at three different stages of pericardiectomy. RESULTS: During the pericardiectomy,the cardiac index[CI,(1.9+/ 0.6),(2.7+/-0.6),(3.0+/-0.5)L.min(-1).m(-2);P<0.05]and stroke volume index[SI,(22.5+/-8.7),(29.9+/-8.5),(30.1+/-8.5)dyn.s.cm(-5).m(2);P<0.05]showed significant improvement,whereas central venous pressure[CVP,(17.1+/-5.0),(13.3+/ 3.9),(12.3+/-3.0)mmHg;P<0.05]decreased significantly. Global end-diastolic volume index[GEDVi,(533+/-156),(580+/-153),(559+/-144)ml.m(-2);P<0.05]increased and stroke volume variation[SVV,(15.6+/-6.1)%,(10.8+/-4.2)%,(9.4+/ 5.4)%;P<0.05]decreased intra-operatively. The majority of the above-mentioned hemodynamic improvements occurred after the resection of pericardium over the left ventricular outflow tract(LVOT). CONCLUSIONS: PiCCO system can serve as a reliable,less invasive hemodynamic monitoring method during pericardiectomy. Resection of the pericardium over the LVOT is the most important step of the pericardiectomy. PMID- 26149148 TI - Influence of Sex on Remifentanil's Cough-prevention Effect during Anesthetic Emergence. AB - OBJECTIVE: To investigate the influence of sex on the cough-preventing effect of target-controlled infusion(TCI)of remifentanil during anesthetic emergence. METHODS: A total of 25 female(group F)and 25 male(group M)patients undergoing thyroidectomy were recruited in the current study. Anesthesia was maintained with sevoflurane and remifentanil TCI.At the end of the surgery,inhalational anesthetics were discontinued,and remifentanil TCI at an effect-site concentration(Ce)of 2.0 ng/ml was maintained during emergence until extubation. The cough score,blood pressure,and heart rate(HR)during peri-extubation period as well as the respiratory rate,calm score,and sore throat score after extubation were evaluated. RESULTS: During extubation,the proportion of patients with no cough or just a single cough was significantly higher in group F than in group M(88% vs. 64%,P=0.047). Mean arterial pressure(P=0.025,P=0.037)and HR(P=0.035)were significantly increased during extubation compared with preoperative levels in group M. CONCLUSIONS: Sex may influence the cough preventing effect of remifentanil TCI during anesthetic emergence. At a Ce of 2.0 ng/ml,remifentanil has better cough-preventing effect and more stable hemodynamic status in females than in males. PMID- 26149149 TI - Effectiveness of Two Training Methods for Avoiding Excessive Inflation of Laryngeal Mask Airway Supreme. AB - OBJECTIVE: To evaluate the effectiveness of two training methods for avoiding excessive inflation of laryngeal mask airway(LMA)Supreme. METHODS: Totally 41 anesthesiologists were randomly divided into hand touch group(H group,n=20)and short-term pressure gauge training group(G group,n=21). Before training,subjects were asked to inflate the cuff of LMA Supreme to two target pressures,30 cmH(2)O and 60 cmH(2)O, according to their own experiences. The actual cuff pressures were recorded as baseline pressures. Subjects in H group then received the training of hand touch:touch the vermilion of the lip and apex nasi with the left ring finger and feel the hardness. A cuff pressure with hardness similar to the vermilion of the lip was defined as 30 cmH(2)O, and similar to the apex nasi as 60 cmH(2)O. Subjects in G group were asked to inflate the cuff with a pressure gauge and feel the hardness of the cuff when the pressure reached 30 cmH(2)O and 60 cmH(2)O. After one-week training,two groups of subjects repeated the cuff inflation test. Actual cuff pressures after training were also recorded and compared with the baseline pressures. Results Actual cuff pressures after training[Group H:(39.7+/-15.7) cmH(2)O(P=0.00);Group G:(26.2+/-13.2) cmH(2)O(P=0.03)]were significantly lower than baseline pressures in both groups when the target cuff pressure was 30 cmH(2)O, and the differences were not statistically significant between these two groups(P=0.06). When the target pressure was 60 cmH(2)O,the actual cuff pressure of H group [(91.1+/ 24.3)cmH(2)O] was significantly higher than that of G group [(58.1+/-15.4) cmH(2)O (P=0.01)]. However,the actual cuff pressure of G group was similar to the target pressure. CONCLUSION: The two training methods are equally effective when the target pressure is 30 cmH(2)O, while short-term pressure gauge training method is superior when the target pressure is 60 cmH(2)O. PMID- 26149150 TI - Identification and Treatment of the Early Form of Neurogenic Pulmonary Edema in Emergency Room. AB - OBJECTIVE: To improve the management of the early neurogenic pulmonary edema(NPE)in patients with non-traumatic cerebral hemorrhage. METHODS: Totally 140 eligible patients with non-traumatic cerebral hemorrhage who were treated in the emergency department of our hospital from October 2008 to October 2014 were divided into two groups:NPE group(n=25)and non-NPE group(n=115). The clinical data were analyzed and compared. RESULTS: Although the mean arterial pressure was similar between these two groups,the median pH and the bicarbonate ion(HCO(3)( ))were significantly lower in the NPE group than in the non-NPE group(pH:7.32 vs.7.39,P=0.002;HCO(3)(-),20.6 mmol/L vs.22.7 mmol/L,P=0.01). Multivariate regression analysis indicated that younger age and higher glucose level were significantly correlated with the early onset of NPE in the NPE group than in the non-NPE group(age:50.1 years vs.65.1 years,P=0.0008;glucose,15.4 mmol/L vs.10.78 mmol/L,P=0.001).There were only 3 patients in all with non-traumatic cerebral hemorrhage happened the fulminant NPE in 1 hour. Within 24 hours after patients visited the emergency room,the condition was improved in 20 of 25 patients in the NPE group. However,5 patients died,among whom 3 patients with fulminant NPE(onset within 1 hour)died due to acute respiratory distress syndrome and complicated with multiple organ failure,and 2 died of cerebral hernia. CONCLUSIONS: NPE is a rare and severe complication in patients with non traumatic cerebral hemorrhage. The possibility of NPE should be considered in relatively young patients with higher glucose and lower blood pH value. Timely prevention and treatment can improve the outcomes. PMID- 26149151 TI - Clinical Etiologies of Fever of Unknown Origin in 500 Cases. AB - OBJECTIVE: To investigate the distribution and change of the causes of fever of unknown origin(FUO). METHODS: The clinical data of 500 inpatients with FUO in our center between December 2003 and June 2014 were retrospectively analyzed. The diagnostic methods,etiologies,and their possible relationship with age,sex,fever duration,and period. RESULTS: Of these 500 FUO patients,452(90.4%)were confirmed to be with fever caused by conditions including infectious diseases [(n=231,46.2%;e.g.tuberculosis(32.9%,76/231)],connective tissue diseases(CTD)(n=99,19.8%),neoplasms(n=58,11.6%),miscellaneous causes(n=64,12.8%). The causes were not identified in 48 cases(9.6%).The proportion of CTD in female patients was significantly higher than that in male patients(26.3% vs. 14.5%,P=0.025),whereas the proportion of neoplasms in male patients was significantly higher than that in female patients(14.5% vs. 8.0%,P=0.001). Infectious diseases was the most common cause in all age groups,CTD ranked the second in the 21-39-year group and 40-59-year group,and neoplasm was the second most coomon cause in the over 60 year group. Thus,the distribution of FUO etiologies significantly differed in different age groups(chi(2)=43.10,P=0.000). The duration of fever in patients with neoplasms [60(28,90)d] was longer than that in patients with infectious diseases [28(21,42)d,Z=-4.168,P=0.000] or CTD [30(21,60)d,Z=-2.406,P=0.016)]. Compared with the level in 2003-2008,the proportion of CTD significantly increased in 2009-2014(13.7% vs. 23.8%,chi(2)=8.598,P=0.003),along with the dicrease of the proportions of infectious diseases,neoplasms and miscellaneous diseases were decreased(all P>0.05). CONCLUSIONS: Infectious diseases(in particular,tuberculosis)remains the major cause of FUO. CTD and neoplasms also play important roles in the development of FUO. The distributions of the FUO etiologies have certain differences in terms of age,sex,duration of fever,and period. PMID- 26149152 TI - Correlation between Plasma Level of Monocyte Chemotactic Protein 1 and Acute Aortic Dissection. AB - OBJECTIVE: To investigate the potential association between monocyte chemotactic protein 1(MCP-1)in plasma and acute aortic dissection(AAD). METHODS: A total of 110 patients with Stanford type A AAD who had received emergent surgical treatment in Xiangya hospital from September 2011 to September 2014 were enrolled in as the study group;meanwhile,110 patients with simple hypertension who had received treatment in department of cardiology were chosen as the control group. The plasma level of MCP-1 was measured and then compared between these two groups. RESULTS: The plasma level of MCP-1 in the study group was(257.79+/ 86.52)pg/ml,which was significantly higher than that in control group [(136.57+/ 48.84)pg/ml](P<0.001). CONCLUSION: There may be a correlation between plasma MCP 1 level and AAD. PMID- 26149153 TI - Risk Factors and Perinatal Outcomes of Velamentous Umbilical Cord Insertion. AB - OBJECTIVE: To explore the risk factors of velamentous umbilical cord insertion(VCI)and the impact of VCI on perinatal outcomes. METHODS: The clinical data of 588 VCI patients who were treated in Beijing Gynecology and Obstetrics Hospital from January 2006 to January 2011 were retrospectively analyzed. In addition,61,143 non-VCI subjects were enrolled as the control group. The possible risk factors of VCI and the impact of VCI on perinatal outcomes were analyzed. In addition,the causes of perinatal deaths were analyzed. RESULTS: The gemellary pregnancy,multiple pregnancy,in vitro fitilization(IVF),placenta praevia,and placenta succenturiata/placenta bipartite were found to be the risk factors of VCI. The incidences of low birth weight,intrauterine growth restriction,asphyxia of newborns,deaths of fetuses or neonates,and single umbilical artery in the VCI group were significantly higher than those in the control group(all P<0.05). In 678 perineonates with VCI,the total death toll of perineonates was 7(1.0%),among whom the death causes included angiorrhexis of placenta praevia(n=1),preterm birth and low birth weight(n=3),torsion of cord(n=1),prolapse of cord(n=1),and placental abruption(n=1). CONCLUSIONS: The risk factors of VCI should be carefully monitored. A diagnosis of VCI,if any,should be correctly made by using modern ultrasound techniques before delivery,so as to lower the mortality of perineonates. PMID- 26149154 TI - Regulatory Effects of Long Non-coding RNA on Tumorigenesis. AB - Long non-coding RNAs(LncRNA)may play a key role in tumorigenesis by regulating gene expression and intervening transcription. Recent studies have demonstrated that a series of patterns including protein modification,chromosomal reconstruction,regulation of target gene expression,transcription intervention,epigenetic modification,and natural antisense transcript are involved in this process. This article reviews recent research advances in this aspect with an attempt to better understand the role of LncRNA in tumorigenesis. PMID- 26149155 TI - Research Advances in the Role of RAS-GTPase-activating Proteins in Tumors. AB - A variety of molecules are involved in tumorigenesis,during which the RAS pathway related molecules play key roles. RAS gene mutations exist in about 30% of human tumors;in some tumors(e.g. pancreatic adenocarcinomas),the mutation rates may rise to 75%-95%. Even in tumors without RAS mutations,the RAS pathway-related molecules can also be highly activated. RAS-GTPase-activating proteins(RASGAPs)are a group of tumor suppressors. They normally turn off RAS pathway by catalyzing the hydrolysis of RAS-GTP. However,the mutation or hypermethylation of their promoters will inactivate their roles and thus provide an alternative mechanism of activating Ras. This article reviews the research advances in the role of RASGAPs in the development of tumors. PMID- 26149156 TI - Improving Risk Communication About Sexually Transmitted Infections: Introduction to the Thematic Issue. PMID- 26149157 TI - The Role of Objective Numeracy and Fluid Intelligence in Sex-Related Protective Behaviors. AB - A wealth of studies has indicated that greater cognitive ability is related to healthier behaviors and outcomes throughout the lifespan. In the present paper, we focus on objective numeracy (ability with numbers) and present findings from a study conducted in the Peruvian Highlands that examines the relations among formal education, numeracy, other more general cognitive skills, and a sex related protective behavior (condom use). Our results show a potential unique protective effect of numeracy on this healthprotective behavior even after accounting for measures of fluid intelligence and potential confounding factors. These results add to a growing literature highlighting the robust protective effect on health behaviors of greater cognitive skills that are enhanced through schooling. Challenges for future research will be identifying the causal mechanisms that underlie these effects and translating this knowledge into effective interventions for improving health. PMID- 26149158 TI - The Views of Young Women on HPV Vaccine Communication in Four European Countries. AB - The Human Papilloma Virus (HPV) is the most common sexually transmitted infection (STI) and can cause cervical cancer. Two vaccines are available to protect against the most common strands of the virus. Vaccination programs differ across Europe but most neglect young adults, who are the group with the highest risk of contracting STIs. Our aim was to explore the views of young women from four European countries-Scotland, Spain, Serbia, and Bulgaria - about the HPV vaccine communication strategy. These countries are characterized by different cervical cancer prevalence and vaccine implementation policies. We conducted focus group discussions with young women (aged 18-26) with various vaccination histories in a purposive sample. We subjected the data to thematic analysis with the purpose of identifying themes related to communication about the HPV vaccine. We recorded the information sources mentioned by participants. Participants discussed numerous sources of vaccine-related information. They approached information critically rather than naively and questioned the sources' trustworthiness and motives. Participants desired transparent information about the risks of the virus and the risks and benefits of the vaccine. These risks and benefits were individualized in view of personal and external factors. Particular aspects of the vaccine and the way information was communicated resulted in feelings of uncertainty. There were notable cross-cultural differences in experiences with HPV vaccine communication. Our results suggest that transparent risk communication about the HPV vaccine is valued by young women. In addition, both individual and culturally-dependent factors influenced experiences with, and preference for information. PMID- 26149159 TI - What Counselors Tell Low-Risk Clients About HIV Test Performance. AB - In 1998, Gigerenzer et al. studied how heterosexual men with low-risk behavior were counseled about the accuracy of HIV test results. Most professional counselors conveyed the illusions that false positives do not occur and that a positive HIV test result means that the client is certainly infected. To help improve counseling quality, the authors provided feedback to all counseling centers in Germany. Sixteen years later we assessed whether HIV counseling in Germany has improved by replicating the original study with an expanded sample of 32 randomly selected counseling centers across the country. Since the original research, the positive predictive value (PPV) of HIV testing for a low-risk client has improved from about 50% to 96%. Hence, among every 26 low-risk clients who test positive, we can expect that one is actually not infected. Whereas test performance has improved over the last 16 years, counseling has not. About half of professional counselors communicated the illusion of certainty for sensitivity (15 of 30), specificity (16 of 30), and the PPV (18 of 30). Only one of the 30 counselors could correctly state the PPV. In what follows, we explain how to improve counselors' and clients' understanding of the PPV by representing the information in terms of natural frequencies rather than conditional probabilities. Doing so has been shown to improve the quality of counseling in different medical settings and may enhance future HIV counseling as well. PMID- 26149160 TI - Communicating HIV Results to Low-Risk Individuals: Still Hazy After All These Years. AB - Revised Centers for Disease Control and Prevention recommendations on HIV testing now promote testing of most risk groups. However, positive results for low-risk individuals are more likely to be false positives than for high-risk individuals, making clear communication of test results even more imperative. In a study, we evaluated current counseling of low-risk test recipients via a sample of 29 HIV hotline counselors from U.S. state and national hotlines. 100% of counselors interviewed failed to provide an accurate conditional HIV risk for low-risk women, but were more likely than a 1998 German sample to report that false positives could occur. In a second study, undergraduates read idealized transcripts of interviews with HIV counselors and computed conditional risk for a low-risk individual. The natural frequency format offered a small but significant improvement in conditional reasoning, comparable to the effect of numerical literacy. Applications for ecologically valid numerical presentations of risk and implications for numeracy are discussed. PMID- 26149161 TI - Gist Representations and Communication of Risks about HIV-AIDS: A Fuzzy-Trace Theory Approach. AB - As predicted by fuzzy-trace theory, people with a range of training-from untrained adolescents to expert physicians-are susceptible to biases and errors in judgment and perception of HIV-AIDS risk. To explain why this occurs, we introduce fuzzy-trace theory as a theoretical perspective that describes these errors to be a function of knowledge deficits, gist-based representation of risk categories, retrieval failure for risk knowledge, and processing interference (e.g., base-rate neglect) in combining risk estimates. These principles explain how people perceive HIV-AIDS risk and why they take risks with potentially lethal outcomes, often despite rote (verbatim) knowledge.For example, people inappropriately generalize the wrong gist about condoms' effectiveness against fluid-borne disease to diseases that are transferred skin-to-skin, such as HPV. We also describe how variation in processing in adolescence (e.g., more verbatim processing compared to adults) can be a route to risk-taking that explains key aspects of why many people are infected with HIV in youth, as well as how interventions that emphasize bottom-line gists communicate risks effectively. PMID- 26149162 TI - Brief Messages to Promote Prevention and Detection of Sexually Transmitted Infections. AB - We review the results of our research program investigating the effects of brief risk awareness interventions for sexually active young adults-the age group most at-risk for sexually transmitted infections (STIs). Our review examines the influence of framed messages, individual differences, and visual aids on key attitudes, behavioral intentions, and health outcomes in three extensive longitudinal studies. Our first study showed that health messages can promote self-reported condom use (screening for STIs) when the messages were framed in positive (negative) terms. This study also showed that adding visual aids to the positive and negative framed messages made them equally and highly effective for promoting self-reported behavior. Visual aids increased self-reported behavior by eliminating the effect of framing on attitudes and behavioral intentions, which in turn influenced self-reported behavior. Our second study showed that visual aids were especially helpful for reducing the effect of message framing among young adults with low numeracy and high graph literacy. Our third study showed that visual aids influenced key attitudes, behavioral intentions, and self reported behavior as much as a validated 8-hour educational program. Overall, our research suggests that well-constructed visual aids provide simple, effective ways of communicating quantitative information about STIs to at-risk young adults. Theoretical mechanisms, public policy implications, and open questions are discussed. PMID- 26149163 TI - Ethical Information Transparency and Sexually Transmitted Infections. AB - Shared decision making is intended to help protect patient autonomy while satisfying the demands of beneficence. In shared decision making, information is shared between health care professional and patient. The sharing of information presents new and practical problems about how much information to share and how transparent that information should be. Sharing information also allows for subtle paternalistic strategies to be employed to "nudge" the patient in a desired direction. These problems are illustrated in two experiments. Experiment 1 (N = 146) suggested that positively framed messages increased the strength of judgments about whether a patient with HIV should designate a surrogate compared to a negatively framed message. A simple decision aid did not reliably reduce this effect. Experiment 2 (N = 492) replicated these effects. In addition, Experiment 2 suggested that providing some additional information (e.g., about surrogate decision making accuracy) can reduce tendencies to think that one with AIDS should designate a surrogate. These results indicate that in some circumstances, nudges (e.g., framing) influence judgments in ways that non nudging interventions (e.g., simple graphs) do not. While non-nudging interventions are generally preferable, careful thought is required for determining the relative benefits and costs associated with information transparency and persuasion. PMID- 26149164 TI - Effective Evidence-Based Programs For Preventing Sexually-Transmitted Infections: A Meta-Analysis. AB - Educational programs for preventing sexually transmitted infections (STIs) have often been implemented in different settings and populations. Mathematica Policy Research and Child Trends conducted a systematic review of 289 evidence-based interventions aiming to reduce STIs and sexual risk behavior in adolescents in the United States. These interventions were published between 1989 and 2012. We conducted a meta-analysis of the interventions that assessed incidence of STIs at follow up, and we identified key characteristics of successful interventions. Results showed that on average interventions reduced incidence roughly from 7 to 6 out of 100 people (17% relative risk reduction (RRR)). Interventions focused on abstinence had no effect, while comprehensive education programs aiming to improve skills and promote safe sexual practices reduced risk by 4 percent (23% RRR). In particular, interventions teaching condom use skills or communication and negotiation skills reduced incidence of STIs by 3 to 4 percent (30% RRR). Finally, interventions decreasing frequency of intercourse or number of sexual partners and interventions increasing condom use also reduced incidence of STIs by 5 to 7 percent (28-36% RRR). Overall properly designed interventions with the above-mentioned characteristics can achieve a 30% reduction of STI incidence. Implications for designing successful interventions to prevent STIs in adolescents are discussed. PMID- 26149166 TI - TBI-the most complex disease in the most complex organ: the CENTER-TBI trial-a commentary. AB - Each year, approximately 2.5 million people experience some form of traumatic brain injury (TBI) in Europe. One million of these are admitted to hospital and 75 000 will die. TBI represents a major cause of death and disability, particularly among those of working age. Substantial investments have been made in an effort to improve diagnosis, management and survival in TBI, but with little success. The Collaborative European Neuro-Trauma Effectiveness Research in TBI (CENTER-TBI) study promises to use the natural variability seen in the management of TBI across Europe with the application of Comparative Effectiveness Research (CER). It will generate repositories of baseline and comprehensive TBI patient data, neuroimaging, neurogenetics and biomarkers, which aim to improve the diagnosis, stratification, management and prognostication of patients with TBI. PMID- 26149165 TI - Behavioral Decision Research Intervention Reduces Risky Sexual Behavior. AB - Although adolescents are at disproportionate risk for sexually transmitted infections, most sex education programs have shown little effect on sexual behavior. An interactive video intervention developed by our team has been identified as one of a few programs that have been documented to reduce sexually transmitted infections in this population. Building on behavioral decision research, we used a mental models approach to interview young women about their sexual decisions, finding, among other things, the strong role of perceived social norms. We based our intervention on these results, aiming to help young women identify and implement personally and socially acceptable decision strategies. A randomized controlled trial found that the video reduced risky sexual behavior and the acquisition of chlamydia infection. We recently revised the video to suit more diverse audiences, and upgraded it to modern standards of cinematography and interactivity. It is now in field trial. PMID- 26149167 TI - SNP array and FISH analysis of a proband with a 22q13.2- 22qter duplication shed light on the molecular origin of the rearrangement. AB - BACKGROUND: In about one third of healthy subjects, the microscopic analysis of chromosomes reveals heteromorphisms with no clinical implications: for example changes in size of the short arm of acrocentric chromosomes. In patients with a pathological phenotype, however, a large acrocentric short arm can mask a genomic imbalance and should be investigated in more detail. We report the first case of a chromosome 22 with a large acrocentric short arm masking a partial trisomy of the distal long arm, characterized by SNP array. We suggest a possible molecular mechanism underlying the rearrangement. CASE PRESENTATION: We report the case of a 15-year-old dysmorphic girl with low grade psychomotor retardation characterized by a karyotype with a large acrocentric short arm of one chromosome 22. Cytogenetic analysis revealed a normal karyotype with a very intense Q fluorescent and large satellite on the chromosome 22 short arm. Fluorescence in situ hybridisation analysis showed a de novo partial trisomy of the 22q13.2-qter chromosome region attached to the short arm of chromosome 22. SNP-array analysis showed that the duplication was 8.5 Mb long and originated from the paternal chromosome. Haplotype analysis revealed that the two paternal copies of the distal part of chromosome 22 have the same haplotype and, therefore, both originated from the same paternal chromosome 22. A possible molecular mechanism that could explain this scenario is a break-induced replication (BIR) which is involved in non-reciprocal translocation events. CONCLUSION: The combined use of FISH and SNP arrays was crucial for a better understanding of the molecular mechanism underlying this rearrangement. This strategy could be applied for a better understanding of the molecular mechanisms underlying cryptic chromosomal rearrangements. PMID- 26149168 TI - Nocturnal Melatonin Profiles in Patients with Delayed Sleep-Wake Phase Disorder and Control Sleepers. AB - A significant delay in the timing of endogenous circadian rhythms has been associated with delayed sleep phase disorder (DSPD). More recently, other mechanisms have also been proposed to account for this disorder. To further explore the etiology of DSPD, the present study compared nocturnal melatonin profiles of 26 DSPD patients (18 males, 8 females; age, 21.73 +/- 4.98 years) and 17 normally timed good sleepers (10 males, 7 females; age, 23.82 +/- 5.23 years) in a time-free, dim-light (<10 lux) laboratory environment. A 30-h modified constant routine with alternating 20-min sleep opportunities and 40 min of enforced wakefulness was used to measure the endogenous melatonin circadian rhythm. Salivary melatonin was sampled half-hourly from 1820 h to 0020 h and then hourly from 0120 h to 1620 h. DSPD patients had significantly later timed melatonin profiles that were delayed by approximately 3 h compared to normal sleepers, and there were no notable differences in the relative duration of secretion between groups. However, melatonin secretion between dim-light melatonin onset (DLMO) and acrophase was less prominent in DSPD patients compared to good sleepers, who showed a more acute initial surge of melatonin following the DLMO. Although the regulatory role of melatonin is unknown, abnormal melatonin profiles have been linked to psychiatric and neurological disorders (e.g., major depression, obsessive compulsive disorder, Parkinson disease). These results therefore suggest that in addition to a delayed endogenous circadian rhythm, a diminished initial surge of melatonin secretion following DLMO may contribute to the etiology of DSPD. PMID- 26149169 TI - The Medicago sativa gene index 1.2: a web-accessible gene expression atlas for investigating expression differences between Medicago sativa subspecies. AB - BACKGROUND: Alfalfa (Medicago sativa L.) is the primary forage legume crop species in the United States and plays essential economic and ecological roles in agricultural systems across the country. Modern alfalfa is the result of hybridization between tetraploid M. sativa ssp. sativa and M. sativa ssp. falcata. Due to its large and complex genome, there are few genomic resources available for alfalfa improvement. RESULTS: A de novo transcriptome assembly from two alfalfa subspecies, M. sativa ssp. sativa (B47) and M. sativa ssp. falcata (F56) was developed using Illumina RNA-seq technology. Transcripts from roots, nitrogen-fixing root nodules, leaves, flowers, elongating stem internodes, and post-elongation stem internodes were assembled into the Medicago sativa Gene Index 1.2 (MSGI 1.2) representing 112,626 unique transcript sequences. Nodule specific and transcripts involved in cell wall biosynthesis were identified. Statistical analyses identified 20,447 transcripts differentially expressed between the two subspecies. Pair-wise comparisons of each tissue combination identified 58,932 sequences differentially expressed in B47 and 69,143 sequences differentially expressed in F56. Comparing transcript abundance in floral tissues of B47 and F56 identified expression differences in sequences involved in anthocyanin and carotenoid synthesis, which determine flower pigmentation. Single nucleotide polymorphisms (SNPs) unique to each M. sativa subspecies (110,241) were identified. CONCLUSIONS: The Medicago sativa Gene Index 1.2 increases the expressed sequence data available for alfalfa by ninefold and can be expanded as additional experiments are performed. The MSGI 1.2 transcriptome sequences, annotations, expression profiles, and SNPs were assembled into the Alfalfa Gene Index and Expression Database (AGED) at http://plantgrn.noble.org/AGED/ , a publicly available genomic resource for alfalfa improvement and legume research. PMID- 26149170 TI - Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: a randomized clinical trial (the BRDME study). AB - BACKGROUND: The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost effectiveness study has been designed to substantiate this hypothesis. AIM: To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness. DESIGN: This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands. OUTCOMES: The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments. PMID- 26149171 TI - Prevalence, risk factors and severity of symptoms of pelvic organ prolapse among Emirati women. AB - BACKGROUND: Similar to other Gulf countries, the society in United Arab Emirates is pro-natal with high parity and high prevalence of macrosomic babies. Therefore, it is possible to have a high prevalence of pelvic organ prolapse (POP). Thus, the aim of this study was to determine the prevalence of POP symptoms in one of the UAE cities. METHODS: A cross-sectional study of all women who attended the three family development centres was conducted in Al-Ain from January 2010 to January 2011. Non-Emirati, pregnant and nulliparous women younger than 30 years were excluded. RESULTS: Out of 482 women who met the inclusion criteria, 429 (89.0%) agreed to fully participate in the study. 127 women (29.6%) reported symptoms of POP (mean age: 38.2 years, range: 18-71). Out of the 127 affected women, a dragging lump was felt occasionally in 68%, sometimes in 19%, most of times in 9% and all the times in 4%. 73% of affected women experienced soreness in the vagina. Around one third had to insert their fingers in the vagina to either start or complete emptying of the bladder or to empty the bowel. Using multivariate analysis, the independent risk factors were history of constipation, level of education, chronic chest disease, nature of occupation, birth weight and body mass index (Odds ratio; 95% Confidence interval): (4.1; 2.3 7.3), (1.7; 1.2-2.3), (2.9; 1.6-5.5), (0.5; 0.4-0.8), (1.7; 1.1-2.5), (1.1; 1.0 1.1), respectively (P < 0.05 for all). CONCLUSION: Symptoms of POP are prevalent among Emirati women. Independent risk factors included history of chronic constipation and chest disease, level of education, job type, birth weight and body mass index. Additional healthcare campaigns are required to educate the public regarding these risk factors. PMID- 26149172 TI - Enter exitrons. AB - Exitrons are exon-like introns located within protein-coding exons. Removal or retention of exitrons through alternative splicing increases proteome complexity and thus adds to phenotypic diversity. PMID- 26149174 TI - Patients will be told cost of missed appointments and may be charged. PMID- 26149173 TI - In vitro and in vivo identification of ABCB1 as an efflux transporter of bosutinib. AB - BACKGROUND: Bosutinib is a recently approved ABL inhibitor. In spite of the well documented effectiveness of BCR-ABL inhibitors in treating chronic myeloid leukemia, development of resistance is a continuous clinical challenge. Transporters that facilitate drug uptake and efflux have been proposed as one potential source of resistance to tyrosine kinase inhibitor treatment. Our aim was to determine which carriers are responsible for bosutinib transport. METHODS: K562S cells overexpressing the drug transporters ABCB1, ABCG2, and SLC22A1 were generated, characterized and used in proliferation assay and intracellular uptake and retention assay (IUR). In vivo experiments were performed in nude mice injected with K562S, K562DOX cells (overexpressing ABCB1), and K562DOX silenced for ABCB1 (K562DOX/sh P-GP). RESULTS: The IUR assay using C-14 bosutinib showed that only ABCB1 was responsible for active bosutinib transport. K562DOX cells showed the lowest intracellular level of bosutinib, while K562DOX cells treated with the ABCB1 inhibitor verapamil showed intracellular bosutinib levels comparable with parental K562S. Proliferation assays demonstrated that K562DOX are resistant to bosutinib treatment while verapamil is able to restore the sensitivity to the drug. Nude mice injected with K562DOX and treated with bosutinib showed very limited response and quickly relapsed after stopping treatment while K562S as well as K562DOX/sh P-GP remained tumor-free. CONCLUSIONS: Our data suggest that the analysis of ABCB1 expression levels might help determine treatment options for patients exhibiting resistance to bosutinib. PMID- 26149175 TI - Usefulness of non-contrast-enhanced MRI with two-dimensional balanced steady state free precession for the acquisition of the pulmonary venous and left atrial anatomy pre catheter ablation of atrial fibrillation: Comparison with contrast enhanced CT in clinical cases. AB - BACKGROUND: To investigate the feasibility of substituting non-contrast-enhanced MR (non-CE-MR) imaging with a two-dimensional (2D) balanced steady-state free precession (b-SSFP) sequence for contrast-enhanced computed tomography (CE-CT) for atrial fibrillation (AF) ablation. METHODS: Fifty-four patients that underwent AF ablation under the guidance of a 3D electro-anatomical mapping system with CE-CT (n = 27) or non-CE-MR images (n = 27) were studied. Procedural results were compared between the two groups. Furthermore, in 22 patients who underwent both CE-CT and non-CE-MRI, two cardiologists independently scored the multiplanar reformatted images on a scale of 1 to 4 (from 1, poor, to 4, excellent). RESULTS: The image score was nearly 0.5 point higher with the CE-CT method. However, the procedural results such as the surface registration error (1.0 [0.8-1.6] mm versus 1.0 [0.8-1.35] mm, P = 0.88) and procedure time (185 [159-199] min versus 185 [142-221] min, P = 0.86) did not significantly differ between the CE-CT and non-CE-MR groups. CONCLUSION: The non-CE-MR method with a 2D-b-SSFP sequence can give us adequate information on AF ablation without any radiation exposure or contrast medium usage PMID- 26149176 TI - [Outpatient suburethral sling in women: Review of the literature]. AB - INTRODUCTION: The aim of this study was to assess efficacy, complication and feasibility of outpatient suburethral slings for stress urinary incontinence in women. MATERIAL AND METHODS: A systematic review of the literature was done from the Pubmed data-base by searching following keywords: suburethral sling, midurethral sling, TVT, TOT, outpatient surgery, day surgery. RESULTS: Seventy eight percent to 88% of patients were continent postoperatively, and 6.8 to 12% of patients were significantly improved. No major complication occurred and minor complications were observed in 7.2 to 19.8% of patients. Eighty to 86.6% of patients experienced no complication. Seventy percent to 100% of patients were discharged on post operative day 0. The satisfaction rate was 89.4 to 95%. CONCLUSION: Outpatient suburethral sling for stress urinary incontinence is suitable, effective, with a low complication rate, and with a high rate of satisfaction. PMID- 26149177 TI - Utilization of light by fucoxanthin-chlorophyll-binding protein in a marine centric diatom, Chaetoceros gracilis. AB - The major light-harvesting pigment protein complex (fucoxanthin-chlorophyll binding protein complex; FCP) was purified from a marine centric diatom, Chaetoceros gracilis, by mild solubilization followed by sucrose density gradient centrifugation, and then characterized. The dynamic light scattering measurement showed unimodality, indicating that the complex was highly purified. The amount of chlorophyll a (Chl a) bound to the purified FCP accounted for more than 60 % of total cellular Chl a. The complex was composed of three abundant polypeptides, although there are nearly 30 FCP-related genes. The two major components were identified as Fcp3 (Lhcf3)- and Fcp4 (Lhcf4)-equivalent proteins based on their internal amino acid sequences and a two-dimensional isoelectric focusing electrophoresis analysis developed in this work. Compared with the thylakoids, the FCP complex showed higher contents of fucoxanthin and chlorophyll c but lower contents of the xanthophyll cycle pigments diadinoxanthin and diatoxanthin. Fluorescence excitation spectra analyses indicated that light harvesting, rather than photosystem protection, is the major function of the purified FCP complex, which is associated with more than 60 % of total cellular Chl a. These findings suggest that the huge amount of Chl bound to the FCP complex composed of Lhcf3, Lhcf4, and an unidentified minor protein has a light-harvesting function to allow efficient photosynthesis under the dim-light conditions in the ocean. PMID- 26149178 TI - New dimeric carbazole-benzimidazole mixed ligands for the stabilization of human telomeric G-quadruplex DNA and as telomerase inhibitors. A remarkable influence of the spacer. AB - The development of G-quadruplex (G4) DNA binding small molecules has become an important strategy for selectively targeting cancer cells. Herein, we report the design and evolution of a new kind of carbazole-based benzimidazole dimers for their efficient telomerase inhibition activity. Spectroscopic titrations reveal the ligands high affinity toward the G4 DNA with significantly higher selectivity over duplex-DNA. The electrophoretic mobility shift assay shows that the ligands efficiently promote the formation of G4 DNA even at a lower concentration of the stabilizing K(+) ions. The TRAP-LIG assay demonstrates the ligand's potential telomerase inhibition activity and also establishes that the activity proceeds via G4 DNA stabilization. An efficient nuclear internalization of the ligands in several common cancer cells (HeLa, HT1080, and A549) also enabled differentiation between normal HFF cells in co-cultures of cancer and normal ones. The ligands induce significant apoptotic response and antiproliferative activity toward cancer cells selectively when compared to the normal cells. PMID- 26149179 TI - Modeling of long range transport pathways for radionuclides to Korea during the Fukushima Dai-ichi nuclear accident and their association with meteorological circulations. AB - The Lagrangian FLEXible PARTicle (FLEXPART) dispersion model and National Centers for Environmental Prediction/Global Forecast System (NCEP/GFS) meteorological data were used to simulate the long range transport pathways of three artificial radionuclides: (131)I, (137)Cs, and (133)Xe, coming into Korean Peninsula during the Fukushima Dai-ichi nuclear accident. Using emission rates of these radionuclides estimated from previous studies, three distinctive transport routes of these radionuclides toward the Korean Peninsula for a period from 10 March to 20 April 2011 were exploited by three spatial scales: 1) intercontinental scale - plume released since mid-March 2011 and transported to the North to arrive Korea on 23 March 2011, 2) global (hemispherical) scale - plume traveling over the whole northern hemisphere passing through the Pacific Ocean/Europe to reach the Korean Peninsula with relatively low concentrations in late March 2011 and, 3) regional scale - plume released on early April 2011 arrived at the Korean Peninsula via southwest sea of Japan influenced directly by veering mesoscale wind circulations. Our identification of these transport routes at three different scales of meteorological circulations suggests the feasibility of a multi-scale approach for more accurate prediction of radionuclide transport in the study area. In light of the fact that the observed arrival/duration time of peaks were explained well by the FLEXPART model coupled with NCEP/GFS input data, our approach can be used meaningfully as a decision support model for radiation emergency situations. PMID- 26149180 TI - Thyroid function abnormalities and cognitive decline. PMID- 26149182 TI - Synthesis of novel cationic spermine-conjugated phosphotriester oligonucleotide for improvement of cell membrane permeability. AB - A spermine-conjugated ethyl phosphotriester oligonucleotide was obtained by solid phase synthesis based on phosphoramidite chemistry. The ethyl phosphotriester linkage was robust to exonuclease digestion and stable in fetal bovine serum. Cell membrane permeability of the spermine-conjugated ethyl phosphotriester oligonucleotide was studied by fluorescence experiments. The effective cell penetrating potency of the spermine-conjugated ethyl phosphotriester oligonucleotide was determined by confocal laser scanning microscopy and measurement of intracellular fluorescence intensity. PMID- 26149183 TI - Design and biological evaluation of novel quinolone-based metronidazole derivatives as potent Cu(2+) mediated DNA-targeting antibacterial agents. AB - A series of novel quinolone-based metronidazole derivatives as new type of antimicrobial agents were developed and characterized. Most of them gave good antibacterial activity towards the Gram-positive and negative bacteria. Noticeably, quinolone derivative 3i exhibited low MIC value of 0.25 MUg/mL against Pseudomonas aeruginosa, which was even superior to reference drugs Norfloxacin, Ciprofloxacin and Clinafloxacin. The further research revealed that compound 3i could intercalate into P. aeruginosa DNA through copper ion bridge to form a steady 3i-Cu(2+)-DNA ternary complex which might further block DNA replication to exert the powerful bioactivities. PMID- 26149184 TI - Clearance Pathways and Tumor Targeting of Imaging Nanoparticles. AB - A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies. PMID- 26149185 TI - Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid arthritis: associations with cytokine profiles, clinical and genetic features. AB - Antibodies against cyclic citrullinated peptides (anti-CCP) are widely used for diagnosis of rheumatoid arthritis (RA). We performed a comparative analysis of antibodies targeting the citrullinating enzyme peptidylarginine deiminase type 4 (anti-PAD4) and mutated citrullinated vimentin (anti-MCV) with anti-CCP autoantibodies in RA patients and examined their relationships with clinical parameters, cytokine profiles and the PADI4 gene. Autoantibodies were examined by enzyme-linked immunosorbent assay (ELISA) in sera of 170 RA patients and 103 controls. Cytokine profiles were measured using a multiplex system. PADI4 polymorphisms (89 G > A, 90 T > C and 92 G > C) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Anti-PAD4, anti-MCV and anti-CCP autoantibodies were detected in 24, 61 and 74% of RA patients, respectively. Positive correlations were observed between anti-PAD4 and disease duration; anti-CCP and erythrocyte sedimentation rate (ESR); anti-MCV and ESR and C-reactive protein. Anti-MCV antibodies were associated with high disease activity score 28 (DAS-28) in early RA. Concentrations of T helper type 1 (Th1) [tumour necrosis factor (TNF)-alpha, interleukin (IL)-12, IL-2, IL-1beta], Th2 (IL-4, IL-6, IL-10, IL-13) and Th17 (IL-17) cytokines were higher in RA than in controls. Th2 and, to a lesser extent, Th1-related cytokines, showed positive correlations with anti-MCV and anti-CCP. The GTG haplotype in PADI4 was associated with anti-CCP and anti-MCV, but not anti-PAD4 antibodies. In conclusion, anti-PAD4 antibodies are detected mainly in established RA, which is in contrast to the early detection of antibodies against citrullinated peptide/proteins (ACPAs). Among autoantibodies, anti-MCV appear to perform better as markers of disease activity. Furthermore, anti-CCP and anti-MCV are associated genetically with the citrullinating enzyme PAD4 and are related strongly to Th1 and Th2 cytokines, suggesting a feed-forward loop between cytokines and ACPA production. PMID- 26149186 TI - Nasopharyngeal bacterial burden and antibiotics: Influence on inflammatory markers and disease severity in infants with respiratory syncytial virus bronchiolitis. AB - OBJECTIVES: Animal studies suggest that RSV increases nasopharyngeal (NP) bacterial colonization facilitating bacterial infections. We investigated the influence of antibiotic treatment and colonization with potentially pathogenic bacteria on inflammatory markers and disease severity in RSV-infected in infants. METHODS: Healthy young infants hospitalized with RSV bronchiolitis (n = 136) and age-matched healthy controls (n = 23) were enrolled and NP samples cultured for potentially pathogenic bacteria including: Gram-positive bacteria (GPB): Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic Streptococcus; and Gram-negative bacteria (GNB): Moraxella catarrhalis and Haemophilus influenzae. Clinical parameters and plasma IL-8, IL-6 and TNF-alpha concentrations were compared according to the bacterial class and antibiotic treatment. RESULTS: Antibiotic treatment decreased by 10-fold NP bacterial recovery. Eighty-one percent of RSV infants who did not receive antibiotics before sample collection were colonized with pathogenic bacteria. Overall, GNB were identified in 21% of patients versus 4% of controls who were mostly colonized with GPB. Additionally, in RSV patients NP white blood cell counts (p = 0.026), and blood neutrophils (p = 0.02) were higher in those colonized with potentially pathogenic bacteria versus respiratory flora. RSV patients colonized with GNB had higher plasma IL-8 (p = 0.01) and IL-6 (p < 0.01) concentrations than controls, and required longer duration of oxygen (p = 0.049). CONCLUSIONS: Infants with RSV bronchiolitis colonized with potentially pathogenic bacteria had increased numbers of mucosal and systemic inflammatory cells. Specifically, colonization with GNB was associated with higher concentrations of proinflammatory cytokines and a trend towards increased disease severity. PMID- 26149187 TI - The role of live poultry movement and live bird market biosecurity in the epidemiology of influenza A (H7N9): A cross-sectional observational study in four eastern China provinces. AB - BACKGROUND: A new reassortant influenza A (H7N9) virus emerged early 2013 in eastern China. Exposure to H7N9 infected poultry at live bird markets (LBM) was implicated as the main risk factor for human infection. We aimed to identify the role of LBM biosecurity indicators and poultry movement in the affected areas. METHODS: A cross-sectional survey was carried out in 24 LBMs at the beginning of H7N9 outbreak in all affected provinces. We used univariable analysis to identify the biosecurity factors associated with the H7N9 presence in LBMs and social network and spatial analysis to quantify the connectivity and geographic variation in the connectivity of poultry movements. RESULTS: Chickens were the predominant poultry species traded by affected LBMs. The presence of H7N9 in LBMs was significantly associated with the type of LBM and with LBMs that sold chicken to other markets. The chicken movements were significantly spatially clustered and was highest in counties from Jiangsu and Anhui provinces. CONCLUSION: LBM biosecurity and chicken movement played an important role in the emergence of H7N9. This study identified highly connected areas in eastern China which continue to report human infections highlighting candidate areas for more detailed epidemiological investigations. PMID- 26149188 TI - Corrigendum: Archaeal amoA and ureC genes and their transcriptional activity in the Arctic Ocean. PMID- 26149189 TI - L-Carnitine supplementation improved clinical status without changing oxidative stress and lipid profile in women with knee osteoarthritis. AB - Considering the pathologic importance of oxidative stress and altered lipid metabolism in osteoarthritis (OA), this study aimed to investigate the effect of l-carnitine supplementation on oxidative stress, lipid profile, and clinical status in women with knee OA. We hypothesized that l-carnitine would improve clinical status by modulating serum oxidative stress and lipid profile. In this randomized double-blind, placebo-controlled trial, 72 overweight or obese women with mild to moderate knee OA were randomly allocated into 2 groups to receive 750 mg/d l-carnitine or placebo for 8 weeks. Dietary intake was evaluated using 24-hour recall for 3 days. Serum malondialdehyde (MDA), total antioxidant capacity (TAC) and lipid profile, visual analog scale for pain intensity, and patient global assessment of severity of disease were assessed before and after supplementation. Only 69 patients (33 in the l-carnitine group and 36 in the placebo group) completed the study. l-Carnitine supplementation resulted in significant reductions in serum MDA (2.46 +/- 1.13 vs 2.16 +/- 0.94 nmol/mL), total cholesterol (216.09 +/- 34.54 vs 206.12 +/- 39.74 mg/dL), and low-density lipoprotein cholesterol (129.45 +/- 28.69 vs 122.05 +/- 32.76 mg/dL) levels compared with baseline (P < .05), whereas these parameters increased in the placebo group. Serum triglyceride, high-density lipoprotein cholesterol, and TAC levels did not change significantly in both groups (P > .05). No significant differences were observed in dietary intake, serum lipid profile, MDA, and TAC levels between groups after adjusting for baseline values and covariates (P > .05). There were significant intragroup and intergroup differences in pain intensity and patient global assessment of disease status after supplementation (P < .05). Collectively, l-carnitine improved clinical status without changing oxidative stress and lipid profile significantly in women with knee OA. PMID- 26149190 TI - Vitamin D deficiency is common among adults in Wallonia (Belgium, 51 degrees 30' North): findings from the Nutrition, Environment and Cardio-Vascular Health study. AB - Data on the vitamin D status of the population of Wallonia (Belgium, 51 degrees 30' North) are scarce. This study was carried out to estimate vitamin D deficiency, identify potential determinants, and analyze their relationship with vitamin D supplementation. We tested the hypothesis that vitamin D deficiency is common in the general population, particularly among subjects without supplementation. Vitamin D deficiency was defined as a serum level of 25 hydroxyvitamin D (25(OH)D) concentration less than 50nmol/L. Data were analyzed from 915 participants of the Nutrition, Environment and Cardio-Vascular Health cross-sectional survey. The median (interquartile range) 25(OH)D level was 53.1 (37.8-69.9) nmol/L, and 44.7% of the subjects were vitamin D deficient. Subjects without vitamin D supplementation were more concerned by vitamin D deficiency than those with supplementation (odds ratio [OR], 3.35; P < .0001). From a multivariate standpoint, the potential determinants of vitamin D deficiency among subjects without vitamin D supplementation were season, specifically spring and winter (OR, 7.36 and 6.44, respectively), obesity (OR, 2.19), low household income (OR, 1.73), and lack of solarium use (OR, 1.79). For subjects with supplementation, the only determinant observed for vitamin D deficiency was obesity (OR, 5.00). This work evidenced the high prevalence of 25(OH)D deficiency in the general population, especially among nonsupplemented subjects with obesity, low household income, and/or lack of light. Vitamin D supplementation looks effective in our population, especially via a stabilization of vitamin D coverage throughout the seasons. The best dietary strategy to achieve optimal 25(OH)D concentrations all year round in the general population requires more research. PMID- 26149191 TI - Mixed exposure to bacterial lipopolysaccharide and seafood proteases augments inflammatory signalling in an airway epithelial cell model (A549). AB - Seafood industry workers exhibit increased prevalence of respiratory symptoms due to exposure to bioaerosols containing a mixture of bioactive agents. In this study, a human pulmonary epithelial cell model (A549) was exposed to mixtures of bacterial lipopolysaccharide (LPS) and protease-activated receptor-2 (PAR-2) agonists H-Ser-Leu-Ile-Gly-Lys-Val-NH2 (SLIGKV-NH2), purified salmon ( Salmo salar) trypsin or purified king crab ( Paralithodes camtschaticus) trypsin. The inflammatory response was measured based on nuclear factor-kappa B (NF-kappaB) activation of transcription in a luciferase reporter gene assay and interleukin 8 (IL-8) secretion in an enzyme-linked immunosorbent assay. We observed that mixtures of SLIGKV-NH2 or trypsins with LPS augmented the activation of NF-kappaB and secretion of IL-8. The effect on IL-8 secretion was synergistic when both trypsins and LPS were used in the lower concentration range. The results demonstrate that exposure to mixtures of agents that are relevant to seafood industry workplaces may lead to increased inflammatory signalling compared with exposure to the individual agents alone. Furthermore, the results indicate that synergism may occur with the combined exposure to seafood trypsins and LPS and is most likely to occur when exposure to either agent is low. PMID- 26149192 TI - Evaluation of DNA damage and DNA repair capacity in occupationally lead-exposed workers. AB - Occupational lead (Pb) exposure remains a significant concern for workers in Turkey. Health hazards of Pb exposure have been investigated in various test systems, but results regarding its potential genotoxic effects on exposed populations are contradictory. In this study, a control group and an exposed group were studied, each consisting of 25 male subjects. Blood lead levels (BLLs) were estimated by graphite furnace atomic absorption spectrometry. Genotoxic effects of Pb exposure were studied in leukocytes by comet and challenge assays. The effect of Pb exposure to DNA repair capacity was evaluated following in vitro hydrogen peroxide exposure. Pb-exposed workers had significantly higher BLLs than the control group ( p < 0.01). DNA damage in exposed workers had a significantly higher percentage of DNA in tail than the control group ( p < 0.05). In the challenge assay, it was found that the mean DNA% repair capacity was significantly decreased in Pb-exposed workers ( p < 0.01). The results indicated that occupational Pb exposure is associated with DNA damage and causes decrease in DNA% repair capacity, indicating a potential health concern for occupationally Pb-exposed populations. PMID- 26149193 TI - Crystal structure of a COG4313 outer membrane channel. AB - COG4313 proteins form a large and widespread family of outer membrane channels and have been implicated in the uptake of a variety of hydrophobic molecules. Structure-function studies of this protein family have so far been hampered by a lack of structural information. Here we present the X-ray crystal structure of Pput2725 from the biodegrader Pseudomonas putida F1, a COG4313 channel of unknown function, using data to 2.3 A resolution. The structure shows a 12-stranded barrel with an N-terminal segment preceding the first beta-strand occluding the lumen of the barrel. Single channel electrophysiology and liposome swelling experiments suggest that while the narrow channel visible in the crystal structure does allow passage of ions and certain small molecules in vitro, Pput2725 is unlikely to function as a channel for hydrophilic molecules. Instead, the presence of bound detergent molecules inside the barrel suggests that Pput2725 mediates uptake of hydrophobic molecules. Sequence alignments and the locations of highly conserved residues suggest the presence of a dynamic lateral opening through which hydrophobic molecules might gain entry into the cell. Our results provide the basis for structure-function studies of COG4313 family members with known function, such as the SphA sphingosine uptake channel of Pseudomonas aeruginosa. PMID- 26149194 TI - Determination of pKa and Hydration Constants for a Series of alpha-Keto Carboxylic Acids Using Nuclear Magnetic Resonance Spectrometry. AB - The determination of the acid-base dissociation constants, and thus the pKa values, of alpha-keto acids such as pyruvic acid is complex because of the existence of these acids in their hydrated and nonhydrated or oxo state. Equilibria involved in the hydration and dehydration of the alpha-keto group of pyruvic acid and three other alpha-keto acids, 3-methyl-2-oxobutanoic acid, 4 methyl-2-oxopentanoic acid, and 2-oxo-2-phenylacetic acid, were investigated by proton and carbon nuclear magnetic resonance spectrometry, at constant ionic strength, 0.15, and 25 degrees C. Dissociation constants for the oxo (pKa(oxo)) and hydrated (pKa(hyd)) acids of each compound were estimated from the change in the degree of hydration with changes in pH and directly from the changes in chemical shifts of various hydrogen and carbons nuclei with pH. alpha-Keto acids showed greater hydration in their acidic forms than their carboxylate forms. The degree of hydration was sensitive to steric and electronic/resonance factors. As expected, the oxo forms of the acids were stronger acids compared with their hydrated analogs, and their dissociation constants were also sensitive to steric and electronic factors. PMID- 26149195 TI - Identifying racial differences in nodular lymphocyte-predominant Hodgkin lymphoma. PMID- 26149203 TI - ? PMID- 26149196 TI - Effects of dexamphetamine-induced dopamine release on resting-state network connectivity in recreational amphetamine users and healthy controls. AB - Dexamphetamine (dAMPH) is not only used for the treatment of attention deficit hyperactivity disorder (ADHD), but also as a recreational drug. Acutely, dAMPH induces release of predominantly dopamine (DA) in the striatum, and in the cortex both DA and noradrenaline. Recent animal studies have shown that chronic dAMPH administration can induce changes in the DA system following long-term exposure, as evidenced by reductions in DA transporters, D2/3 receptors and endogenous DA levels. However, only a limited number of studies have investigated the effects of dAMPH in the human brain. We used a combination of resting-state functional magnetic resonance imaging (rs-fMRI) and [(123)I]IBZM single-photon emission computed tomography (SPECT) (to assess baseline D2/3 receptor binding and DA release) in 15 recreational AMPH users and 20 matched healthy controls to investigate the short-, and long-term effects of AMPH before and after an acute intravenous challenge with dAMPH. We found that acute dAMPH administration reduced functional connectivity in the cortico-striatal-thalamic network. dAMPH induced DA release, but not DA D2/3 receptor binding, was positively associated with connectivity changes in this network. In addition, acute dAMPH reduced connectivity in default mode networks and salience-executive-networks networks in both groups. In contrast to our hypothesis, no significant group differences were found in any of the rs-fMRI networks investigated, possibly due to lack of sensitivity or compensatory mechanisms. Our findings thus support the use of ICA based resting-state functional connectivity as a tool to investigate acute, but not chronic, alterations induced by dAMPH on dopaminergic processing in the striatum. PMID- 26149202 TI - Loss and rebuilding: A qualitative study of late diagnosis of cleft palate. AB - PURPOSE: To explore the experiences of parents whose child received a late diagnosis of cleft palate (>24 hr after birth). DESIGN AND METHODS: Parents of 17 children and three nurses specialised in cleft care (specialist nurses) took part in a qualitative, semi-structured interview. Framework analysis was applied to data. RESULTS: Loss and rebuilding was an overarching concept-from the crescendo leading up to the bombshell of diagnosis, followed by the aftermath of dealing with the child's long-term condition. PRACTICE IMPLICATIONS: Specialist nurses can help parents to trust healthcare professionals and to feel confident in their ability to nurture by listening, informing, and supporting. PMID- 26149204 TI - What should be taken into account during study on immunoregulatory effects of helminths: a critical analyzing on "Downregulation of immune responses in asthmatic patients by ES products of Marshallagia marshalli". PMID- 26149205 TI - Endometrial Ablation in Women With Abnormal Uterine Bleeding Related to Ovulatory Dysfunction: A Cohort Study. AB - STUDY OBJECTIVE: To evaluate the efficacy and safety of endometrial ablation (EA) for the treatment of abnormal uterine bleeding (AUB) associated with ovulatory dysfunction. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic medical center. PATIENTS: Women with AUB who underwent EA during an 8-year period. INTERVENTIONS: EA by radiofrequency or thermal balloon ablation techniques. MEASUREMENTS AND MAIN RESULTS: Women with AUB were divided into 2 groups: irregular bleeding with ovulatory dysfunction (AUB-O) or regular heavy bleeding related to a primary endometrial disorder (AUB E). Outcome measures included rates of amenorrhea and treatment failure (ie, need for reablation or hysterectomy). Outcomes were compared between groups using survival analyses and chi-square tests. Known confounders were adjusted for using Cox and logistic regression models. Five-year cumulative treatment failure rates were 11.7% (95% confidence interval [CI], 6.5%-16.9%) for AUB-O and 12.3% (95% CI, 8.4%-16.2%) for AUB-E (p = .62). The unadjusted hazard ratio for treatment failure was 0.87 (95% CI, 0.72-1.05, p = .16). After adjusting for known risk factors for failure, the hazard ratio was 1.48 (95% CI, 0.82-2.65, p = .19). The rates of amenorrhea were 11.8% for AUB-O and 13.8% for AUB-E with an unadjusted odds ratio of 0.84 (95% CI, 0.48-1.48, p = .55). After adjusting for factors for amenorrhea after EA, the odds ratio was 1.08 (95% CI, 0.62-1.84, p =.78). No pregnancies or endometrial cancers occurred after EA. CONCLUSION: EA is effective in women with AUB-O and can be used as an alternative to hysterectomy or in patients with contraindications to medical management of AUB-O. PMID- 26149206 TI - Graphical modeling for gene set analysis: A critical appraisal. AB - Current demand for understanding the behavior of groups of related genes, combined with the greater availability of data, has led to an increased focus on statistical methods in gene set analysis. In this paper, we aim to perform a critical appraisal of the methodology based on graphical models developed in Massa et al. (2010) that uses pathway signaling networks as a starting point to develop statistically sound procedures for gene set analysis. We pay attention to the potential of the methodology with respect to the organizational aspects of dealing with such complex but highly informative starting structures, that is pathways. We focus on three themes: the translation of a biological pathway into a graph suitable for modeling, the role of shrinkage when more genes than samples are obtained, the evaluation of respondence of the statistical models to the biological expectations. To study the impact of shrinkage, two simulation studies will be run. To evaluate the biological expectation we will use data from a network with known behavior that offer the possibility of carrying out a realistic check of respondence of the model to changes in the experimental conditions. PMID- 26149207 TI - Near-Roadway Air Pollution and Coronary Heart Disease: Burden of Disease and Potential Impact of a Greenhouse Gas Reduction Strategy in Southern California. AB - BACKGROUND: Several studies have estimated the burden of coronary heart disease (CHD) mortality from ambient regional particulate matter <= 2.5 MUm (PM2.5). The burden of near-roadway air pollution (NRAP) generally has not been examined, despite evidence of a causal link with CHD. OBJECTIVE: We investigated the CHD burden from NRAP and compared it with the PM2.5 burden in the California South Coast Air Basin for 2008 and under a compact urban growth greenhouse gas reduction scenario for 2035. METHODS: We estimated the population attributable fraction and number of CHD events attributable to residential traffic density, proximity to a major road, elemental carbon (EC), and PM2.5 compared with the expected disease burden if the population were exposed to background levels of air pollution. RESULTS: In 2008, an estimated 1,300 CHD deaths (6.8% of the total) were attributable to traffic density, 430 deaths (2.4%) to residential proximity to a major road, and 690 (3.7%) to EC. There were 1,900 deaths (10.4%) attributable to PM2.5. Although reduced exposures in 2035 should result in smaller fractions of CHD attributable to traffic density, EC, and PM2.5, the numbers of estimated deaths attributable to each of these exposures are anticipated to increase to 2,500, 900, and 2,900, respectively, due to population aging. A similar pattern of increasing NRAP-attributable CHD hospitalizations was estimated to occur between 2008 and 2035. CONCLUSION: These results suggest that a large burden of preventable CHD mortality is attributable to NRAP and is likely to increase even with decreasing exposure by 2035 due to vulnerability of an aging population. Greenhouse gas reduction strategies developed to mitigate climate change offer unexploited opportunities for air pollution health co benefits. PMID- 26149208 TI - Spatial distribution and risk assessment of heavy metals in sediments of Shuangtaizi estuary, China. AB - In order to evaluate the spatial distribution and potential ecological risk of Pb, Cu, Zn, Cd, and Hg, the surface sediments were collected from 18 sites in the Shuangtaizi estuary. The concentrations of Pb, Cu, Zn, Cd, and Hg were analyzed by atomic absorption spectrophotometry and atomic fluorescence spectrometry after digestion. The particle sizes of the sediments were analyzed using a laser diffraction particle size analyzer. The results show that the heavy metal contents in the sediments are observed in the following order: Zn (18.25 126.75mg/kg)>Pb (4.38-9.65mg/kg)>Cu (1.80-17.68mg/kg)>Cd (0.241-0.764mg/kg)>Hg (0.007-0.021mg/kg). In comparison with the concentrations of heavy metals in other regions, the concentrations of Pb, Cu, and Zn in the Shuangtaizi estuary are generally low, and the Cd concentrations are close to those reported in other regions. Both the potential ecological risk index and the geoaccumulation index reveal that the heavy metal pollution in Shuangtaizi estuary is mainly dominated by Cd. PMID- 26149210 TI - A Comparison of Different Volumes of Articaine for Inferior Alveolar Nerve Block for Molar Teeth with Symptomatic Irreversible Pulpitis. AB - INTRODUCTION: Achieving anesthesia in mandibular molar teeth with irreversible pulpitis is very difficult. The aim of this study was to compare the efficacy of 1.8 mL and 3.6 mL articaine for an inferior alveolar nerve block (IANB) when treating molars with symptomatic irreversible pulpitis. METHODS: In a randomized, double-blind clinical trial, 82 first mandibular molar teeth with symptomatic irreversible pulpitis randomly received conventional IANB injection either with 1 (1.8 mL) or 2 cartridges (3.6 mL) of 4% articaine with 1:100,000 epinephrine. The patients recorded their pain before and during access cavity preparation as well as during root canal instrumentation using a Heft-Parker visual analog scale. No or mild pain was considered as successful anesthesia. Data were analyzed by t and chi-square tests. RESULTS: Eighty patients were eligible to participate in this study, which showed that 3.6 mL articaine provided a significantly higher success rate (77.5%) of IANBs compared with 1.8 mL of the same anesthetic solution (27.5%) although neither group had 100% successful anesthesia (P < .001). CONCLUSIONS: Increasing the volume of articaine provided a significantly higher success rate of IANBs in mandibular first molar teeth with symptomatic irreversible pulpitis, but it did not result in 100% anesthetic success. PMID- 26149211 TI - An electrogenic nitric oxide reductase. AB - Nitric oxide reductases (Nors) are members of the heme-copper oxidase superfamily that reduce nitric oxide (NO) to nitrous oxide (N2O). In contrast to the proton pumping cytochrome oxidases, Nors studied so far have neither been implicated in proton pumping nor have they been experimentally established as electrogenic. The copper-A-dependent Nor from Bacillus azotoformans uses cytochrome c551 as electron donor but lacks menaquinol activity, in contrast to our earlier report (Suharti et al., 2001). Employing reduced phenazine ethosulfate (PESH) as electron donor, the main NO reduction pathway catalyzed by Cu(A)Nor reconstituted in liposomes involves transmembrane cycling of the PES radical. We show that Cu(A)Nor reconstituted in liposomes generates a proton electrochemical gradient across the membrane similar in magnitude to cytochrome aa3, highlighting that bacilli using Cu(A)Nor can exploit NO reduction for increased cellular ATP production compared to organisms using cNor. PMID- 26149212 TI - miR-216a may inhibit pancreatic tumor growth by targeting JAK2. AB - This study was aimed to investigate miR-216a expression in pancreatic cancer and determine its effects on proliferation. miR-216a was found downregulated in pancreatic cancer tissues as compared to benign pancreatic lesions. JAK2 was identified as a miR-216a gene target. Further, in vivo treatment of PANC-1 tumors with miR-216a reduced JAK2 protein levels in the tumor and reduced tumor volume. In conclusion, miR-216a may function as a tumor suppressor regulating pancreatic cancer cells by targeting the JAK/STAT pathway. Further studies with a larger number of patient samples are necessary to fully explore the diagnostic and therapeutic potential of miR-216a for pancreatic cancer. PMID- 26149213 TI - MicroRNA-410 promotes cell proliferation by targeting BRD7 in non-small cell lung cancer. AB - miR-410 acts as an oncogene or tumor suppressor gene in some malignancies. However, its role in NSCLC is still unknown. In this study, we showed that the expression of miR-410 was up-regulated in both human NSCLC tissues and cells. Overexpression of miR-410 promoted cell proliferation, migration, and invasion of NSCLC. In addition, bromodomain-containing protein 7 (BRD7) was a direct target of miR-410. MiR-410-mediated downregulation of BRD7 led to increase Akt phosphorylation. Inhibition of Akt phosphorylation can rescue the effect of miR 410 on NSCLC cell. The expression of BRD7 was downregulated in NSCLC and was inversely expressed with miR-410 in NSCLC. Our data provided new knowledge regarding the role of miR-410 in the lung cancer progression. PMID- 26149214 TI - The human ATF1 rs11169571 polymorphism increases essential hypertension risk through modifying miRNA binding. AB - Activating transcription factor 1 (ATF1) may be involved in essential hypertension (EH) by induction of NADPH oxidase 1 (NOX1) and radical oxygen species (ROSs) production. Abnormal expression of ATF1 was found in EH in previous microarray analysis. Here we tested whether a single nucleotide polymorphism (SNP) located in the 3'-untranslated region (3'UTR) of ATF1 was associated with EH susceptibility by affecting microRNA (miRNA) binding. In silico analysis indicated that rs11169571 (T>C) was a candidate SNP to modulate miRNA: ATF1 mRNA complex, with the greatest changed energy for hsa-miR-1283, and the luciferase reporter analysis showed that miR-1283 inhibited the activity of the reporter vector carrying -T allele, but not the -C allele. In addition, inhibition of miR-1283 in HA-VSMCs enhanced the expression of ATF1 mRNA as well as the ROS levels. Further case-control study showed that rs11169571 was significantly associated with increased risk of EH. Finally, we observed an increased ATF1 protein level in peripheral blood of EH patients with CC carriers compared to TT carriers of rs11169571, with an intermediate ATF1 level in TC carriers. These results suggested that rs11169571 of ATF1 gene may be associated with EH, and the SNP-modified posttranscriptional gene regulation by miRNAs could be a potentially pathogenetic mechanism of EH. PMID- 26149215 TI - Residues in the acetyl CoA binding site of pyruvate carboxylase involved in allosteric regulation. AB - We have examined the roles of Asp1018, Glu1027, Arg469 and Asp471 in the allosteric domain of Rhizobium etli pyruvate carboxylase. Arg469 and Asp471 interact directly with the allosteric activator acetyl coenzyme A (acetyl CoA) and the R469S and R469K mutants showed increased enzymic activity in the presence and absence of acetyl CoA, whilst the D471A mutant exhibited no acetyl CoA activation. E1027A, E1027R and D1018A mutants had increased activity in the absence of acetyl CoA, but not in its presence. These results suggest that most of these residues impose restrictions on the structure and/or dynamics of the enzyme to affect activity. PMID- 26149216 TI - ILT4 drives B7-H3 expression via PI3K/AKT/mTOR signalling and ILT4/B7-H3 co expression correlates with poor prognosis in non-small cell lung cancer. AB - Immunoglobulin-like transcript (ILT) 4 is critical for the inhibitory function of certain immune cells. We previously demonstrated that ILT4 is over-expressed in human non-small cell lung cancer (NSCLC) cells and is involved in tumour evasion via an unknown mechanism. In this report, we demonstrate that ILT4 increases the expression of the co-inhibitory molecule B7-H3 through PI3K/AKT/mTOR signalling. In primary human NSCLC tissues, a significant positive relationship is observed between ILT4 and B7-H3 expression. ILT4/B7-H3 co-expression is significantly associated with a reduction in T infiltrating lymphoid cells and lower overall survival. In summary, ILT4 increases B7-H3 expression and ILT4/B7-H3 co expression may be involved in NSCLC progression. PMID- 26149217 TI - Wide Carbon Nanopores as Efficient Sites for the Separation of SF6 from N2. AB - SF6 and SF6-N2 mixed gases are used widely as insulators, but such gases have high greenhouse gas potential. The separation of SF6 from SF6-N2 mixed gases is an inevitable result of their use. Single-walled carbon nanohorns (CNHs) were used here for a fundamental study of the separation of SF6 and N2. The diameters of the interstitial and internal nanopores of the CNHs were 0.7 and 2.9 nm, respectively. The high selectivity of SF6 over N2 was observed only in the low pressure regime in the interstitial 0.7 nm nanopores; the selectively was significantly decreased at higher pressures. In contrast, the high selectivity was maintained over the entire pressure range in the internal 2.9-nm nanopores. These results showed that the wide carbon nanopores were efficient for the separation of SF6 from the mixed gas. PMID- 26149218 TI - Cross-national perspectives about weight-based bullying in youth: nature, extent and remedies. AB - BACKGROUND: No cross-national studies have examined public perceptions about weight-based bullying in youth. OBJECTIVES: To conduct a multinational examination of public views about (i) the prevalence/seriousness of weight-based bullying in youth; (ii) the role of parents, educators, health providers and government in addressing this problem and (iii) implementing policy actions to reduce weight-based bullying. METHODS: A cross-sectional survey of adults in the United States, Canada, Iceland and Australia (N = 2866). RESULTS: Across all countries, weight-based bullying was identified as the most prevalent reason for youth bullying, by a substantial margin over other forms of bullying (race/ethnicity, sexual orientation and religion). Participants viewed parents and teachers as playing major roles in efforts to reduce weight-based bullying. Most participants across countries (77-94%) viewed healthcare providers to be important intervention agents. Participants (65-87%) supported government augmentation of anti-bullying laws to include prohibiting weight-based bullying. Women expressed higher agreement for policy actions than men, with no associations found for participants' race/ethnicity or weight. Causal beliefs about obesity were associated with policy support across countries. CONCLUSIONS: Across countries, strong recognition exists of weight-based bullying and the need to address it. These findings may inform policy-level actions and clinical practices concerning youth vulnerable to weight-based bullying. PMID- 26149219 TI - Sperm storage in Hemidactylus mabouia: Morphological and ultrastructural aspects of a reproductive strategy. AB - Sperm storage is a common phenomenon in most female reptiles. Evidence of sperm storage is based on the observation that female fertilization occurs even when females are separated from males, as well as the presence of agglomerates of spermatozoa in specific regions of the oviducts. Lizards are capable of storing sperm in the uterine tube, vagina, or in both regions. However, representatives of the Gekkonidae family commonly store spermatozoa in the uterine tube, which is considered an ancestral character state for Squamates. Using comparative techniques of light, transmission and scanning electron microscopy, we observed stored sperm organized in compact bundles with their heads facing the bottom of the crypts of the uterine tube, indicating chemotactic attraction. The alignment and packing of spermatozoa in Hemidactylus mabouia indicates that the process of evacuation of the crypts for fertilization may be related to the passage of the egg that exerts mechanical pressure against the walls of the uterine tube, causing its distension and the release of spermatozoa. We conclude that the sperm storage region and the morphological organization of the crypts in the uterine tube of H. mabouia is similar to other previously studied species of lizards, supporting the notion that sperm storage is a common reproductive strategy among female reptiles. PMID- 26149220 TI - The effect of selected staining techniques on bull sperm morphometry. AB - Sperm morphometry has some value as an indicator of reproductive capacity in males. In laboratory practice a variety of slide-staining methods are used during morphological evaluation of semen to predict male fertility. The aim of this study was to determine the effect of staining of semen using four different techniques on the morphometry of the bull sperm cell. The material for the study consisted of semen collected from test bulls of the Black-and-White variety of Holstein-Friesians. The results obtained in the study indicate differences in the dimensions of bull sperm heads when different slide staining techniques were used. The most similar results for sperm head dimensions were obtained in the case of SpermBlue((r)) and eosin+gentian violet complex, although statistically significant differences were found between all the staining techniques. Extreme values were noted for the other staining techniques - lowest for the Papanicolaou and highest for silver nitrate, which may indicate more interference in the cell by the reagents used in the staining process. However, silver nitrate staining was best at identifying the structures of the sperm cell. Hence it is difficult to determine which of the staining methods most faithfully reveals the dimensions and shape of the bull sperm. PMID- 26149221 TI - Extended spectrum beta-lactamase producing Escherichia coli in broiler breeding roosters: Presence in the reproductive tract and effect on sperm motility. AB - Extended spectrum beta-lactamases (ESBL)-producing Escherichia coli have emerged worldwide in animal husbandry and they were reported from different ecosystems. The purpose of this study was firstly, to investigate the presence of ESBL producing E. coli in the gastrointestinal (GIT) and reproductive (RT) tracts of broiler breeding roosters, and secondly to study the impact of an ESBL-producing E. coli on artificially infected semen. A total of seventeen ESBL-producing E. coli strains were isolated from the gastrointestinal and reproductive tracts of nine broiler breeding roosters. All isolates were identified to the species level by API 20E system and MALDI-TOF, serotyped, and genetically characterized for ESBL production. Semen was artificially infected with E. coli ATCC25922 or with an ESBL-producing E. coli strain recovered from the reproductive tract. A computer aided semen analyzer (CASA) was used to compare different spermatozoa motility parameters in each sample. All ESBL-producing E. coli isolates could not be typed with the currently used sera and they were harboring a blaCTX-M gene alone or in combination with a blaTEM gene. The semen quality was notably less affected in samples infected with ESBL-producing E. coli strain compared to the control and sample infected with E. coli ATCC25922. The present study revealed that ESBL-producing E. coli can be isolated from both reproductive and digestive tracts of broiler breeding roosters. Contamination of the reproductive tract with ESBL-producing E. coli could lead to contamination of semen and could be an important factor in the dissemination of ESBL-producing E. coli in poultry. PMID- 26149222 TI - Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field magnetic resonance imaging. AB - BACKGROUND: In patients with a glioblastoma (GBM), few unselected data exists using actual standard adjuvant treatment and contemporary surgical techniques like iMRI. Aim of study is to assess impact of EoR and recurrent surgery on survival and outcome. METHODS: We assessed a consecutive unselected series of 170 surgeries for GBM (2008-2014) applying intraoperative MRI (iMRI). All patients received adjuvant radio-chemo-therapy. Overall-survival (OS), progression free survival (PFS), complications and new permanent neurological deficits (nPND) were assessed. Uni- and multivariate-cox-regression-models were calculated. RESULTS: Mean follow-up was 40mo. GTR was intended in 82% and achieved in 77% of these cases. A nPND was found in 7% of patients. In multivariate cox-regression, GTR (HR:0.6, P<0.024) and absence of MGMT methylation (HR:1.6, P<0.042) was significantly associated with PFS. We found no difference in PFS after primary surgery and recurrent surgery. Concerning OS, in multivariate assessment an un methylated MGMT-promotor (HR2.0, P<0.01) and presence of a complication (HR1.7, P<0.06) were negative prognosticators. Only GTR was significantly beneficial for OS (HR0.4, P<0.028) compared to a failed GTR and a STR. Repeated surgery for recurrent disease was positively associated with OS (HR0.6, P<0.06). CONCLUSIONS: Surgery in a contemporary setup using iMRI, brain mapping and modern adjuvant treatment, has a higher OS and lower complication rates as previously published. A maximum but safe resection should be the goal of surgery since a perioperative complication significantly decreases OS. Recurrent surgery has a beneficial effect on OS without an increase of complications. PMID- 26149223 TI - The role of single-stage posterior debridement, interbody fusion with titanium mesh cages and short-segment instrumentation in thoracic and lumbar spinal tuberculosis. AB - BACKGROUND: The aim of this paper was to retrospectively analyze the clinical efficacy and feasibility of thoracic and lumbar spinal tuberculosis treated by single-stage posterior debridement, interbody fusion with titanium mesh cages (TMC), and combined short-segment instrumentation. METHODS: Fifteen patients with no more than two vertebral bodies involving thoracic and lumbar tuberculosis were collected from January 2006 to January 2010, performed by single-stage posterior debridement, interbody fusion with TMC and posterior short-segment fixation. The clinical efficacy was evaluated based on the data of the 10-point Visual Analogue Scale (VAS), neurological status, kyphosis angle, erythrocyte sedimentation rate, and C-reactive protein, which were collected at a certain time. RESULTS: The average duration of surgery was 135 minutes. All the patients were followed up for a period ranging from 18 to 48 months (mean 28.9+/-6.44 months). The VAS score was improved from 8.47+/-1.13 (range 7-10) before surgery to 2.1+/-1.7 (range 0-2) after surgery. Correction of segmental kyphotic deformity was 24.2+/ 6.59 degrees . Neither the postoperative change of the position of titanium mesh cage nor any posterior instrumentation failure was recorded. The situation of 13 patients with incomplete neurologic lesions before surgery was improved after surgery. CONCLUSIONS: Patients with thoracic and lumbar spinal tuberculosis can be successfully treated by posterior debridement, interbody fusion with TMC combining short-segment instrumentation. The presence of the TMC anteriorly at the site of tubercular spondylitis has no negative influence on the course of infection healing, and additionally they stabilize the affected segment maintaining sufficient sagittal profile. PMID- 26149226 TI - Bringing delirium into the 21st century: will physicians get the app out? AB - Invited commentary for International Psychogeriatrics on Tieges Z, Stiobhairt A, Scott K, Suchorab K, Weir A, Parks S, Shenkin S and MacLullich A. Development of a smartphone application for the objective detection of attentional deficits in delirium. International Psychogeriatrics. 2015 Mar 6:1-12. PMID- 26149224 TI - Intravitreal TSG-6 suppresses laser-induced choroidal neovascularization by inhibiting CCR2+ monocyte recruitment. AB - Choroidal neovascularization (CNV) is the hallmark of wet age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly. Although the pathogenesis of CNV is not clear, a number of studies show that ocular-infiltrating macrophages and inflammation play a critical role in the development of CNV. TNFalpha-stimulated gene/protein (TSG)-6 is a multifunctional endogenous protein that has anti-inflammatory activities partly by regulating macrophage activation. Therefore, we here investigated the therapeutic potential of TSG-6 in a rat model of CNV induced by laser photocoagulation. Time course analysis showed that the expression of VEGF and pro-inflammatory cytokines in the choroid was up-regulated early after laser injury, and gradually decreased to baseline over 14 days. An intravitreal injection of TSG-6 suppressed the expression of VEGF and pro-inflammatory cytokines including CCL2, and reduced the size of CNV. Also, the number of Iba(+) and CCR2(+) cells including infiltrating macrophages was markedly lower in the CNV lesion of TSG-6-treated eyes. Further analysis identified CCR2(+) CD11b(+) CD11c(+) cells and CCR2(+) CD11b(-)CD11c(+) cells as the cell populations that were increased by laser injury and reduced by TSG-6 treatment. Together, the results demonstrate that TSG-6 inhibits inflammation and CCR2(+) monocyte recruitment into the choroid, and suppresses the development of CNV. PMID- 26149225 TI - Development and Validation of an Algorithm to Identify Planned Readmissions From Claims Data. AB - BACKGROUND: It is desirable not to include planned readmissions in readmission measures because they represent deliberate, scheduled care. OBJECTIVES: To develop an algorithm to identify planned readmissions, describe its performance characteristics, and identify improvements. DESIGN: Consensus-driven algorithm development and chart review validation study at 7 acute-care hospitals in 2 health systems. PATIENTS: For development, all discharges qualifying for the publicly reported hospital-wide readmission measure. For validation, all qualifying same-hospital readmissions that were characterized by the algorithm as planned, and a random sampling of same-hospital readmissions that were characterized as unplanned. MEASUREMENTS: We calculated weighted sensitivity and specificity, and positive and negative predictive values of the algorithm (version 2.1), compared to gold standard chart review. RESULTS: In consultation with 27 experts, we developed an algorithm that characterizes 7.8% of readmissions as planned. For validation we reviewed 634 readmissions. The weighted sensitivity of the algorithm was 45.1% overall, 50.9% in large teaching centers and 40.2% in smaller community hospitals. The weighted specificity was 95.9%, positive predictive value was 51.6%, and negative predictive value was 94.7%. We identified 4 minor changes to improve algorithm performance. The revised algorithm had a weighted sensitivity 49.8% (57.1% at large hospitals), weighted specificity 96.5%, positive predictive value 58.7%, and negative predictive value 94.5%. Positive predictive value was poor for the 2 most common potentially planned procedures: diagnostic cardiac catheterization (25%) and procedures involving cardiac devices (33%). CONCLUSIONS: An administrative claims based algorithm to identify planned readmissions is feasible and can facilitate public reporting of primarily unplanned readmissions. PMID- 26149227 TI - Percutaneous Fluoroscopic-Guided Endomyocardial Delivery in an Experimental Model of Left Ventricular Assist Device Support. AB - Endomyocardial delivery in the setting of active left ventricular assist device (LVAD) support has rarely been studied. The objective was to establish a protocol for endomyocardial injections during LVAD support without compromising mechanical circulation. LVAD implantation was performed in four pigs. A curved needle catheter was percutaneously inserted into the right carotid artery and positioned into the left ventricle under fluoroscopic guidance. In the setting of increasing LVAD flows (2.3-3.1 l/min), percutaneous methylene blue dye administration into the myocardium proceeded without complications in all pigs. Transection of excised hearts revealed an anterior, lateral, inferior, and septal wall distribution of methylene blue documenting injections in all four regions of the left ventricle. Ex vivo, the catheter could be maneuvered close to the LVAD inflow cannula despite augmentation of LVAD flow up to 5 l/min. Endomyocardial injections during LVAD support was found to be feasible and safe with the curved needle catheter. PMID- 26149228 TI - Bile acid-conjugated chondroitin sulfate A-based nanoparticles for tumor-targeted anticancer drug delivery. AB - Chondroitin sulfate A-deoxycholic acid (CSA-DOCA)-based nanoparticles (NPs) were produced for tumor-targeted delivery of doxorubicin (DOX). The hydrophobic deoxycholic acid (DOCA) derivative was conjugated to the hydrophilic chondroitin sulfate A (CSA) backbone via amide bond formation, and the structure was confirmed by (1)H-nuclear magnetic resonance (NMR) analysis. Loading the DOX to the CSA-DOCA NPs resulted in NPs with an approximately 230nm mean diameter, narrow size distribution, negative zeta potential, and relatively high drug encapsulation efficiency (up to 85%). The release of DOX from the NPs exhibited sustained and pH-dependent release profiles. The cellular uptake of DOX from the CSA-DOCA NPs in CD44 receptor-positive human breast adenocarcinoma MDA-MB-231 cells was reduced when co-treated with free CSA, indicating the interaction between CSA and the CD44 receptor. The lower IC50 value of DOX from the CSA-DOCA NPs compared to the DOX solution was also probably due to this interaction. Moreover, the ability of the developed NPs to target tumors could be inferred from the in vivo and ex vivo near-infrared fluorescence (NIRF) imaging results in the MDA-MB-231 tumor-xenografted mouse model. Both passive and active strategies appear to have contributed to the in vivo tumor targetability of the CSA-DOCA NPs. Therefore, these CSA-DOCA NPs could further be developed into a theranostic nanoplatform for CD44 receptor-positive cancers. PMID- 26149229 TI - Low dose tPA plus annexin A2 combination attenuates tPA delayed treatment associated hemorrhage and improves recovery in rat embolic focal stroke. AB - We previously have shown that tissue type plasminogen activator (tPA) in combination with its receptor annexin A2 (rA2) protein significantly improved tPA thrombolytic efficacy. In this study we aimed to examine the therapeutic effects of the combination when treated at delayed 4-hour window after stroke compared to standard conventional tPA alone in an embolic focal stroke rat model. We compared effects of intravenous tPA alone (10 mg/kg) versus a combination of low-dose tPA (5 mg/kg) plus 10 mg/kg rA2. Totally 152 rats were used. Our results showed that: (1) at 24 h after stroke, the combination slightly reduced brain infarction compared to saline (9.2% reduction), and tPA (7.4% reduction), although the reductions did not reach statistical significance; while the combination significantly reduced (22.2% reduction) the conventional tPA-elevated intracerebral hemorrhagic (ICH) transformation; (2) at 7 days after stroke, the combination significantly attenuated conventional tPA alone-elevated iron deposition at peri-lesion area (68.2% reduction); (3) at 28 days after stroke, the combination significantly improved performance of adhesive tape-removal test, which was accompanied by a significantly higher micro vessel density at peri- infarct areas compared to conventional tPA alone group.In conclusion, compared to conventional tPA alone, when treated at delayed 4-hour after stroke, the combination of low-dose tPA plus rA2 therapy provides a safer profile by lowering risk of ICH transformation and improves neurological function recovery after stroke. PMID- 26149230 TI - Age effect in generating mental images of buildings but not common objects. AB - Imagining a familiar environment is different from imagining an environmental map and clinical evidence demonstrated the existence of double dissociations in brain damaged patients due to the contents of mental images. Here, we assessed a large sample of young and old participants by considering their ability to generate different kinds of mental images, namely, buildings or common objects. As buildings are environmental stimuli that have an important role in human navigation, we expected that elderly participants would have greater difficulty in generating images of buildings than common objects. We found that young and older participants differed in generating both buildings and common objects. For young participants there were no differences between buildings and common objects, but older participants found easier to generate common objects than buildings. Buildings are a special type of visual stimuli because in urban environments they are commonly used as landmarks for navigational purposes. Considering that topographical orientation is one of the abilities mostly affected in normal and pathological aging, the present data throw some light on the impaired processes underlying human navigation. PMID- 26149231 TI - Sensitivity of frontal beta oscillations to reward valence but not probability. AB - Reward feedback elicits a brief increase in power in the high-beta frequency range of the human electroencephalogram (EEG) over frontal areas of the scalp, but the functional role of this oscillatory activity remains unclear. An observed sensitivity to reward expectation (HajiHosseini, Rodriguez-Fornells, and Marco Pallares, 2012; [2]) suggests that reward-related beta may index a reward prediction error (RPE) signal for reinforcement learning. To investigate this possibility we reanalyzed EEG data from two prior experiments that revealed RPEs in the human event-related brain potential (Holroyd and Krigolson, 2007 [12]; Holroydet al., 2008 [13]). We found that feedback stimuli that indicated reward, when compared to feedback stimuli that indicated no-reward, elicited relatively more beta power (20-30 Hz) over a frontal area of the scalp. However, beta power was not sensitive to feedback probability. These results indicate that reward related beta does not index an RPE but rather relates to a different reward processing function. PMID- 26149232 TI - Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents. AB - Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation. PMID- 26149233 TI - The effects of intracerebroventricular infusion of apelin-13 on reproductive function in male rats. AB - Apelin is a novel bioactive peptide as the endogenous ligand for APJ. Apelin and APJ have also been identified in the testis, hypothalamic nuclei such as arcuate, supraoptic and paraventricular nuclei, implicating roles in the control of reproduction. Therefore, the present study was designed to investigate the effects of chronic central infusion of apelin-13 on LH, FSH and testosterone levels and testis morphology. 21 Wistar-Albino male rats received continuous intracerebroventricular infusion via Alzet osmotic mini pumps filled artificial cerebrospinal fluid (vehicle) or apelin-13 at concentrations of 1 or 10 nmol (10 MUl/h) for seven days. At the last 90 min of the infusion period, the blood samples were collected at 15 min intervals (0-90 min) for LH and FSH analyses. At the last sampling point, the blood samples were analyzed for testosterone levels. Infusion of high dose apelin-13 significantly suppressed LH release compared with the vehicle values at 30, 60 and 75 min (p<0.05). However, FSH levels did not significantly differ among the groups. Serum testosterone levels in high dose apelin-13 group were statistically lower than the control group (p<0.05). In addition, histological examination showed that infusion of high dose apelin-13 significantly decreased the number of Leydig cells compared with the control and lower dose apelin-13 groups (p<0.05, p<0.01). Our results suggest that apelin-13 may play a role in the central regulation and decreases testosterone release by suppressing LH secretion. Thus, antagonists of the apelin receptor may, therefore, be useful for pharmaceuticals in the treatment of infertility. PMID- 26149234 TI - Electronic Transport via Homopeptides: The Role of Side Chains and Secondary Structure. AB - Many novel applications in bioelectronics rely on the interaction between biomolecules and electronically conducting substrates. However, crucial knowledge about the relation between electronic transport via peptides and their amino-acid composition is still absent. Here, we report results of electronic transport measurements via several homopeptides as a function of their structural properties and temperature. We demonstrate that the conduction through the peptide depends on its length and secondary structure as well as on the nature of the constituent amino acid and charge of its residue. We support our experimental observations with high-level electronic structure calculations and suggest off resonance tunneling as the dominant conduction mechanism via extended peptides. Our findings indicate that both peptide composition and structure can affect the efficiency of electronic transport across peptides. PMID- 26149235 TI - FunRich proteomics software analysis, let the fun begin! AB - Protein MS analysis is the preferred method for unbiased protein identification. It is normally applied to a large number of both small-scale and high-throughput studies. However, user-friendly computational tools for protein analysis are still needed. In this issue, Mathivanan and colleagues (Proteomics 2015, 15, 2597 2601) report the development of FunRich software, an open-access software that facilitates the analysis of proteomics data, providing tools for functional enrichment and interaction network analysis of genes and proteins. FunRich is a reinterpretation of proteomic software, a standalone tool combining ease of use with customizable databases, free access, and graphical representations. PMID- 26149236 TI - Water transport inside carbon nanotubes mediated by phonon-induced oscillating friction. AB - The emergence of the field of nanofluidics in the last decade has led to the development of important applications including water desalination, ultrafiltration and osmotic energy conversion. Most applications make use of carbon nanotubes, boron nitride nanotubes, graphene and graphene oxide. In particular, understanding water transport in carbon nanotubes is key for designing ultrafiltration devices and energy-efficient water filters. However, although theoretical studies based on molecular dynamics simulations have revealed many mechanistic features of water transport at the molecular level, further advances in this direction are limited by the fact that the lowest flow velocities accessible by simulations are orders of magnitude higher than those measured experimentally. Here, we extend molecular dynamics studies of water transport through carbon nanotubes to flow velocities comparable with experimental ones using massive crowd-sourced computing power. We observe previously undetected oscillations in the friction force between water and carbon nanotubes and show that these oscillations result from the coupling between confined water molecules and the longitudinal phonon modes of the nanotube. This coupling can enhance the diffusion of confined water by more than 300%. Our results may serve as a theoretical framework for the design of new devices for more efficient water filtration and osmotic energy conversion devices. PMID- 26149237 TI - Controlled steering of Cherenkov surface plasmon wakes with a one-dimensional metamaterial. AB - In the Cherenkov effect a charged particle moving with a velocity faster than the phase velocity of light in the medium radiates light that forms a cone with a half angle determined by the ratio of the two speeds. Here, we show that by creating a running wave of polarization along a one-dimensional metallic nanostructure consisting of subwavelength-spaced rotated apertures that propagates faster than the surface plasmon polariton phase velocity, we can generate surface plasmon wakes, a two-dimensional analogue of Cherenkov radiation. The running wave of polarization travels with a speed determined by the angle of incidence and the photon spin angular momentum of the incident radiation. By changing either one of these properties we demonstrate controlled steering of the Cherenkov surface plasmon wakes. PMID- 26149238 TI - Metamaterials: Steering surface plasmon wakes. PMID- 26149239 TI - Nanofluidics: Phonon modes for faster flow. PMID- 26149241 TI - Retroperitoneal course of iliohypogastric, ilioinguinal, and genitofemoral nerves: A study to improve identification and excision during triple neurectomy. AB - Triple neurectomy of the iliohypogastric (IHN), ilioinguinal (IIN), and genitofemoral (GFN) nerves is an available treatment option for chronic groin pain when conservative measures are ineffective. This research study attempted to define the variability of IHN, IIN, and GFN by categorizing variation and establishing a relationship to clinically significant landmarks. 22 cadavers (43 specimens) were dissected. Age, gender, ethnicity, BMI, and pertinent medical history were recorded for each specimen. Nerve emergence, insertion, and split points were measured in relation to clinically significant landmarks. Retroperitoneal trajectories of IHN, IIN, and GFN were analyzed and categorized based on nerve branching patterns. IIN and IHN had three branching patterns - type A (47%) in which the IIH and IIN exit as separate branches; type B (26%) in which the IIH and IIN exit as a single bundle and split; and type C (28%) in which the IIH and IIN exit and do not split. The GFN had three branching patterns -type 1 (50%) in which the GFN exited from the psoas major and then split into the genital and femoral branches; type 2 (30%) in which the GFN exited and did not split; and type 3 (20%) in which the GFN exited the psoas major already split into the genital and femoral branches. Variations in the IHN, IIN, and GFN nerves outlined in this study will provide surgeons with clinically useful information aiding in successful and efficient localization of these nerves during retroperitoneal procedures, including laparoscopic triple neurectomy. PMID- 26149240 TI - Mechanical coordination in motor ensembles revealed using engineered artificial myosin filaments. AB - The sarcomere of muscle is composed of tens of thousands of myosin motors that self-assemble into thick filaments and interact with surrounding actin-based thin filaments in a dense, near-crystalline hexagonal lattice. Together, these actin myosin interactions enable large-scale movement and force generation, two primary attributes of muscle. Research on isolated fibres has provided considerable insight into the collective properties of muscle, but how actin-myosin interactions are coordinated in an ensemble remains poorly understood. Here, we show that artificial myosin filaments, engineered using a DNA nanotube scaffold, provide precise control over motor number, type and spacing. Using both dimeric myosin V- and myosin VI-labelled nanotubes, we find that neither myosin density nor spacing has a significant effect on the gliding speed of actin filaments. This observation supports a simple model of myosin ensembles as energy reservoirs that buffer individual stochastic events to bring about smooth, continuous motion. Furthermore, gliding speed increases with cross-bridge compliance, but is limited by Brownian effects. As a first step to reconstituting muscle motility, we demonstrate human beta-cardiac myosin-driven gliding of actin filaments on DNA nanotubes. PMID- 26149242 TI - Metabolomic Responses of Human Hepatocytes to Emodin, Aristolochic Acid, and Triptolide: Chemicals Purified from Traditional Chinese Medicines. AB - The present study was undertaken to investigate the metabolic responses of human liver cells HL-7702 on chemicals purified from traditional Chinese medicine: emodin, triptolide, and aristolochic acid. Cytotoxicity tests demonstrated a dose dependent toxic effect of emodin, triptolide, and aristolochic acid on HL7702 cells for 48 h. Emodin (14 MUM), aristolochic acid (12 MUg/mL), or triptolide (18 nM) was individually administrated to HL7702 and cell samples were collected after 48 h for metabolites extraction and analysis. Pattern recognition analysis reflected the significant difference in metabolic profiles between chemical treated groups and the control group. Finally, eight metabolites including N1 acetylspermidine, Glu Gly, N-undecanoylglycine, C16 sphinganine, sphinganine, glutathione, l-palmitoylcarnitine, and elaidic carnitine were detected as potential common biomarkers. Three pathways including sphinganine metabolism, fatty acid oxidation, and oxidative stress were identified. Our findings indicated that metabolomics would be an efficient approach to understand the molecular mechanism of hepatotoxicity induced by chemicals. PMID- 26149243 TI - An Economic Evaluation of a Weight Loss Intervention Program for People with Serious Mental Illnesses Taking Antipsychotic Medications. AB - Individuals with serious mental illnesses suffer from obesity and cardiometabolic diseases at high rates, and antipsychotic medications exacerbate these conditions. While studies have shown weight loss and lifestyle interventions can be effective in this population, few have assessed intervention cost effectiveness. We present results from a 12-month randomized controlled trial that reduced weight, fasting glucose, and medical hospitalizations in intervention participants. Costs per participant ranged from $4365 to $5687. Costs to reduce weight by one kilogram ranged from $1623 to $2114; costs to reduce fasting glucose by 1 mg/dL ranged from $467 to $608. Medical hospitalization costs were reduced by $137,500. PMID- 26149244 TI - Population Pharmacokinetic Model of Cabozantinib in Patients with Medullary Thyroid Carcinoma and Its Application to an Exposure-Response Analysis. AB - BACKGROUND AND OBJECTIVES: Cabozantinib is a tyrosine kinase inhibitor approved in the USA and EU for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC). The indicated cabozantinib dose is 140 mg/day, with dose modifications allowed for patients who develop adverse events (AEs). The analysis objective was to develop a population pharmacokinetic (PopPK) model in MTC patients and to use the model for exposure-response (ER) analysis of dose modifications. METHODS: A PopPK model for cabozantinib was developed using data from three clinical trials (2079 evaluations from 289 patients), including a randomized, double-blind, placebo-controlled phase III study of patients with progressive, metastatic MTC. The PopPK model predictions [model-predicted steady state area under the plasma concentration-time curve (AUCss,pred)] were used for an ER analysis of the time to first dose modification. RESULTS: The final PopPK model was a one-compartment model with first-order absorption and first-order elimination. Estimated cabozantinib apparent oral clearance (CL/F) and apparent volume of distribution (V c/F) were 106 L/day [+/-2.98 % relative standard error (RSE)] (males) and 349 L (+/-2.73 % RSE), respectively. CL/F was reduced by 22 % (to 83 L/day) in females. Sex and body mass index (BMI) were significant covariates that combined contributed 15 % to the variability in cabozantinib CL/F, but did not warrant dose adjustment. Higher cabozantinib AUCss,pred was correlated to an increased risk of early dose modification and a lower average dose through to Day 85. Early cabozantinib dose modification was not associated with a reduction in progression-free survival (PFS). CONCLUSION: A PopPK model was developed for cabozantinib pharmacokinetics in MTC patients. Higher cabozantinib exposure was associated with earlier first dose modification and a lower average administered dose through to Day 85. Early first dose modification did not appear to impact PFS. PMID- 26149245 TI - Simultaneous determination of carboprost methylate and its active metabolite carboprost in dog plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application to a pharmacokinetic study. AB - A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using positive/negative electrospray ionization (ESI) switching for the simultaneous quantitation of carboprost methylate and carboprost in dog plasma has been developed and validated. After screening, the esterase inhibitor, dichlorvos was added to the whole blood at a ratio of 1:99 (v/v) to stabilize carboprost methylate during blood collection, sample storage and LLE. Indomethacin was added to plasma to inhibit prostaglandins synthesis after sampling. After liquid-liquid extraction of 500MUL plasma with ethyl ether-dichloromethane (75:25, v/v), analytes and internal standard (IS), alprostadil-d4, were chromatographed on a CAPCELL PAK Phenyl column (150*2.0mm, 5MUm) using acetonitrile-5mM ammonium acetate as mobile phase. Carboprost methylate was detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 400.5->329.3; the carboprost and IS were detected by negative ion electrospray ionization followed by MRM of the transitions at m/z 367.2 >323.2, and 357.1->321.2, respectively. The method was linear for both analytes in the concentration range 0.05-30ng/mL with intra- and inter-day precisions (as relative standard deviation) of <=6.75% and accuracy (as relative error) of <=7.21% and limit of detection (LOD) values were 10 and 20pg/mL, respectively. The method was successfully applied to a pharmacokinetic study of the analytes in beagle dogs after intravaginal administration of a suppository containing 0.5mg carboprost methylate. PMID- 26149246 TI - Organic solvent-free air-assisted liquid-liquid microextraction for optimized extraction of illegal azo-based dyes and their main metabolite from spices, cosmetics and human bio-fluid samples in one step. AB - Air-assisted liquid-liquid microextraction (AALLME) has unique capabilities to develop as an organic solvent-free and one-step microextraction method, applying ionic-liquids as extraction solvent and avoiding centrifugation step. Herein, a novel and simple eco-friendly method, termed one-step air-assisted liquid-liquid microextraction (OS-AALLME), was developed to extract some illegal azo-based dyes (including Sudan I to IV, and Orange G) from food and cosmetic products. A series of experiments were investigated to achieve the most favorable conditions (including extraction solvent: 77MUL of 1-Hexyl-3-methylimidazolium hexafluorophosphate; sample pH 6.3, without salt addition; and extraction cycles: 25 during 100s of sonication) using a central composite design strategy. Under these conditions, limits of detection, linear dynamic ranges, enrichment factors and consumptive indices were in the range of 3.9-84.8ngmL(-1), 0.013-3.1MUgmL( 1), 33-39, and 0.13-0.15, respectively. The results showed that -as well as its simplicity, fastness, and use of no hazardous disperser and extraction solvents- OS-AALLME is an enough sensitive and efficient method for the extraction of these dyes from complex matrices. After optimization and validation, OS-AALLME was applied to estimate the concentration of 1-amino-2-naphthol in human bio-fluids as a main reductive metabolite of selected dyes. Levels of 1-amino-2-naphthol in plasma and urinary excretion suggested that this compound may be used as a new potential biomarker of these dyes in human body. PMID- 26149247 TI - Determination of galangin in rat plasma by UPLC and pharmacokinetic study. AB - In this study, a simple, sensitive, and robust analytical method based on ultra performance liquid chromatography (UPLC) has been developed for the determination of galangin in rat plasma using diazepam as internal standard (IS). After sample preparation by a simple liquid-liquid extraction, chromatography was performed on an Acquity UPLC BEH C18 column (2.1mm*50mm, 1.7MUm particle size) and ultraviolet detection set at a wavelength of 360nm. The method was linear over the concentration range 10-1000ng/mL with a lower limit of quantification (LLOQ) of 10ng/mL. Inter- and intra-day precision (RSD %) were all within 9.5% and the accuracy (RE %) was equal or lower than 8.9%. Recoveries of galangin and IS were more than 78.3%. Stability studies showed that galangin was stable under a variety of storage conditions. The method was successfully applied to a pharmacokinetic study involving oral administration of galangin to rats. PMID- 26149248 TI - Validation of a UPLC-MS/MS method for the simultaneous determination of E6005, a phosphodiesterase 4 inhibitor, and its metabolite in human plasma. AB - E6005, a novel phosphodiesterase 4 inhibitor, is currently under clinical development for the treatment of atopic dermatitis. As ER-392710 (M11), a hydrolyzed metabolite, is a main metabolite, a simultaneous assay method for quantification of E6005 and M11 in human plasma has been developed and validated using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC MS/MS). E6005, M11, and each deuterium-labeled compound used as internal standard were extracted from 100MUL human plasma by solid phase extraction then chromatographed on an Acquity UPLC BEH C18 column (100mm*2.1mm i.d., 1.7MUm) under gradient elution. The analytes were detected by selected reaction monitoring in the positive ion mode with the mass transition of m/z 473.1/163.0 and m/z 459.1/149.0 for E6005 and M11, respectively. E6005 and M11 were quantifiable ranging from 1 to 200ng/mL with no carryover. Accuracy and precision in intra- and inter-batch reproducibility assays were within the acceptance criteria recommended by the regulatory bioanalytical guidelines. Various stability assessments including possible conversion of E6005 to M11 were thoroughly performed to demonstrate the stability of E6005 and M11 in human blood and plasma. The method was successfully applied to support clinical trials. PMID- 26149249 TI - Pelarspovirus, a proposed new genus in the family Tombusviridae. AB - Currently, the family Tombusviridae encompasses thirteen viral genera that contain single-stranded, positive-sense RNA genomes and isometric virions; the exception being the genus Umbravirus, whose members do not encode a coat protein (CP). A new genus, tentatively named Pelarspovirus, is proposed to be added to this family and would include five members, with Pelargonium line pattern virus recommended as the type species. Viruses assigned to this proposed genus have monopartite genomes encoding five open reading frames (ORFs) that include two 5' proximal replication proteins, two centrally located movement proteins (MP1 and MP2) and a 3'-proximal CP that, at least for pelargonium line pattern virus (PLPV), has been shown to act also as suppressor of RNA silencing. Distinguishing characteristics of these viruses include i) production of a single, tricistronic subgenomic RNA for expression of MP and CP genes, ii) presence of a non-AUG start codon (CUG or GUG) initiating the MP2 ORF, iii) absence of AUG codons in any frame between the AUG initiation codons of MP1 and CP genes, and iv) sequence based phylogenetic clustering of all encoded proteins in separate clades from those of other family members. PMID- 26149251 TI - Analysis of deficiencies in care following cholecystectomy. AB - INTRODUCTION: Failure To Rescue was first defined in patients who died due to a complication following (open) cholecystectomy but research into the relevant factors has been scarce. This study was designed to determine a chronological sequence of deficiencies in care. METHODS: Adult patients who died under the care of a surgeon following cholecystectomy in Queensland were identified from the Australian and New Zealand Audit of Surgical Mortality (ANZASM) database. RESULTS: Not unexpectedly, this is a high-risk patient population: median age of the 48 patients was 74.5 years and the median number of comorbidities and American Society of Anesthesiologists class was 4. Death occurred on postoperative day 6. Most deaths occurred at the end of the week. Over 80% of deaths followed emergency cholecystectomy. In almost half the patients, there were no deficiencies in care. Most common deficiency was during postoperative management (i.e. Failure To Rescue), however, significant deficiencies also arose prior to surgical admission; choice and timing of intervention as well as intraoperative decision-making. CONCLUSION: Surgeons who perform cholecystectomy need to be aware of the levels at which deficiencies arise given that many may be preventable. PMID- 26149252 TI - New international review supports community water fluoridation as an effective and safe dental health promotion measure. PMID- 26149253 TI - Employee factors associated with interest in improving sun protection in an Australian mining workforce. AB - BACKGROUND: As Australia experiences moderate to extreme levels of ultraviolet radiation from the sun, high participation in sun protection behaviour is required to minimise the risk of developing skin cancer. Understanding factors associated with interest in improving sun protection will enable employers to increase enrolment in sun protection programs. METHOD: A cross-sectional survey was conducted at mining sites in rural Australia. The survey assessed employee demographics, stages of change and health-belief model variables, sun protection behaviour, and preferences for improving sun protection. RESULTS: Overall, 897 employees participated: 73% were male and 47% were classed as being at high risk of ultraviolet-related illnesses. Although 24% of high-risk participants wanted to increase their sun protection practices, only 6% wanted employer-provided sun protection assistance. Marital status and recent experience of sunburn were associated with desire to improve sun protection. Over 50% of the high-risk participants who did not want to increase their sun protection and did not want assistance were in the pre-contemplative stage of change. Self-efficacy was associated with desire to improve sun protection while susceptibility was associated with desire for assistance. CONCLUSION: The use of sun protection behaviours among this sample was low. Many employees at high risk of ultraviolet radiation exposure do not believe their approach to sun protection needs changing. SO WHAT?: Workplace health promotion programs need to educate employees about susceptibility to ultraviolet radiation exposure and develop employees' self-efficacy for sun protection behaviours. These findings can inform the content development of sun protection communication strategies targeting employees. PMID- 26149254 TI - Challenges to establishing successful partnerships in community health promotion programs: local experiences from the national implementation of healthy eating activity and lifestyle (HEALTM) program. AB - ISSUE ADDRESSED: Community-based programs to address physical activity and diet are seen as a valuable strategy to reduce risk factors for chronic disease. Community partnerships are important for successful local implementation of these programs but little is published to describe the challenges of developing partnerships to implement health promotion programs. The aim of this study was to explore the experiences and opinions of key stakeholders on the development and maintenance of partnerships during their implementation of the HEALTM program. METHOD: Semi-structured interviews with key stakeholders involved in implementation of HEALTM in four local government areas. The interviews were transcribed verbatim and analysed thematically. RESULTS: Partnerships were vital to the success of the local implementation. Successful partnerships occurred where the program met the needs of the partnering organisation, or could be adapted to do so. Partnerships took time to develop and were often dependent on key people. Partnering with organisations that had a strong influence in the community could strengthen existing relationships and success. In remote areas partnerships took longer to develop because of fewer opportunities to meet face to face and workforce shortages and this has implications for program funding in these areas. CONCLUSION: Partnerships are important for the successful implementation of community preventive health programs. They take time to develop, are dependent on the needs of the stakeholders and are facilitated by stable leadership. SO WHAT?: An understanding of the role of partnerships in the implementation of community health programs is important to inform several aspects of program delivery, including flexibility in funding arrangements to allow effective and mutually beneficial partnerships to develop before the implementation phase of the program. It is important that policy makers have an understanding of the time it takes for partnerships to develop and to take this into consideration when programs are funded and implemented in the community. PMID- 26149255 TI - Unhealthy product sponsorship of Australian national and state sports organisations. AB - ISSUE ADDRESSED: Marketing of products harmful to the health of children has been found to be prolific, and occurs across multiple media platforms and in several settings, including organised sport, thus potentially undermining the health benefits inherent in sports participation. Through website audits, this study investigated the nature and extent of unhealthy food, beverage, alcohol and gambling sponsorship across peak Australian sporting organisations. METHODS: A structured survey tool identified and assessed sponsoring companies and products displayed on the websites of the 53 national and state/territory sport governing bodies in Australia receiving government funding. Identified products were categorised as healthy or unhealthy, based on criteria developed by health experts. RESULTS: There was a total of 413 websites operated by the 53 sports, with 1975 company or product sponsors identified. Overall, 39 sports had at least one unhealthy sponsor, and 10% of all sponsors were rated as unhealthy. Cricket had the highest percent of unhealthy sponsors (27%) and the highest number of unhealthy food and beverage sponsors (n=19). Rugby Union (n=16) and Australian Football (n=4) had the highest numbers of alcohol and gambling sponsors respectively. CONCLUSIONS: Sponsorship of Australian sport governing bodies by companies promoting unhealthy food and beverage, alcohol and gambling products is prevalent at the state/territory and national level. SO WHAT?: Regulatory guidelines should be established to limit such sponsorship and ensure that it is not translated into promotions that may reach and influence children. PMID- 26149256 TI - Key beliefs of hospital nurses' hand-hygiene behaviour: protecting your peers and needing effective reminders. AB - ISSUES ADDRESSED: Hand hygiene in hospitals is vital to limit the spread of infections. This study aimed to identify key beliefs underlying hospital nurses' hand-hygiene decisions to consolidate strategies that encourage compliance. METHODS: Informed by a theory of planned behaviour belief framework, nurses from 50 Australian hospitals (n=797) responded to how likely behavioural beliefs (advantages and disadvantages), normative beliefs (important referents) and control beliefs (barriers) impacted on their hand-hygiene decisions following the introduction of a national '5 moments for hand hygiene' initiative. Two weeks after completing the survey, they reported their hand-hygiene adherence. Stepwise regression analyses identified key beliefs that determined nurses' hand-hygiene behaviour. RESULTS: Reducing the chance of infection for co-workers influenced nurses' hygiene behaviour, with lack of time and forgetfulness identified as barriers. CONCLUSIONS: Future efforts to improve hand hygiene should highlight the potential impact on colleagues and consider strategies to combat time constraints, as well as implementing workplace reminders to prompt greater hand hygiene compliance. SO WHAT?: Rather than emphasising the health of self and patients in efforts to encourage hand-hygiene practices, a focus on peer protection should be adopted and more effective workplace reminders should be implemented to combat forgetting. PMID- 26149258 TI - Diffusion-weighted MRI of kidneys in healthy volunteers and living kidney donors. AB - AIM: To establish the normal apparent diffusion coefficient (ADC) values in healthy kidneys, comparing them with the literature, and assessing the correlation between ADC values, creatinine blood level, and glomerular filtration rate (GFR). MATERIALS AND METHODS: Twenty-four healthy volunteers and 26 living kidney donors were examined on a 1.5 T magnetic resonance imaging (MRI) unit. Two diffusion-weighted imaging (DWI) sequences were included in the study protocol (protocol 1 with 16 b-values, protocol 2 with 10 b-values) before the examination blood and urine samples were collected. The GFR was calculated using Cockcroft & Gault and MDRD (Modification of Diet In Renal Disease) formulas and the ADC values were measured separately for the cortex and medulla of each kidney by two independent observers. All statistical analyses were performed using the STATISTICA (version 10.0) software package. Data were analysed using an unpaired t-test; p < 0.05 indicated a statistically significant difference. RESULTS: The average ADC value for protocol 1 for the cortex was 2.26 * 10(-3) mm(2)/s, for the medulla 2.21 * 10(-3) mm(2)/s. In protocol 2, the respective values were 2.13 * 10(-3) mm(2)/s and 2.06 * 10(-3) mm(2)/s. Neither statistically significant interobserver differences nor correlation between ADC values, GFR, and creatinine serum level were observed. CONCLUSION: The reference ADC values were established. The measurements show high interobserver consistency. The differences in ADC values reported in the literature suggest dependence on the equipment and methodology and point to the necessity of obtaining ADC norms for each MRI unit. PMID- 26149259 TI - Negative results: negative perceptions limit their potential for increasing reproducibility. AB - Negative results are an important building block in the development of scientific thought, primarily because most likely the vast majority of data is negative, i.e., there is not a favorable outcome. Only very limited data is positive, and that is what tends to get published, albeit alongside a sub-set of negative results to emphasize the positive nature of the positive results. Yet, not all negative results get published. Part of the problem lies with a traditional mind set and rigid publishing frame-work that tends to view negative results in a negative light, or that only tends to reward scientists primarily for presenting positive findings. This opinion piece indicates that in addition to a deficient mind-set, there are also severe limitations in the availability of publishing channels where negative results could get published. PMID- 26149261 TI - AVCC 1990-2015--A journal to combine antiviral biology and antiviral chemistry enters the third era. PMID- 26149260 TI - A large-scale genomic approach affords unprecedented resolution for the molecular epidemiology and evolutionary history of contagious caprine pleuropneumonia. AB - Contagious caprine pleuropneumonia (CCPP), caused by Mycoplasma capricolum subsp. capripneumoniae (Mccp), is a devastating disease of domestic goats and of some wild ungulate species. The disease is currently spreading in Africa and Asia and poses a serious threat to disease-free areas. A comprehensive view of the evolutionary history and dynamics of Mccp is essential to understand the epidemiology of CCPP. Yet, analysing the diversity of genetically monomorphic pathogens, such as Mccp, is complicated due to their low variability. In this study, the molecular epidemiology and evolution of CCPP was investigated using a large-scale genomic approach based on next-generation sequencing technologies, applied to a sample of strains representing the global distribution of this disease. A highly discriminatory multigene typing system was developed, allowing the differentiation of 24 haplotypes among 25 Mccp strains distributed in six genotyping groups, which showed some correlation with geographic origin. A Bayesian approach was used to infer the first robust phylogeny of the species and to date the principal events of its evolutionary history. The emergence of Mccp was estimated only at about 270 years ago, which explains the low genetic diversity of this species despite its high mutation rate, evaluated at 1.3 * 10( 6) substitutions per site per year. Finally, plausible scenarios were proposed to elucidate the evolution and dynamics of CCPP in Asia and Africa, though limited by the paucity of Mccp strains, particularly in Asia. This study shows how combining large-scale genomic data with spatial and temporal data makes it possible to obtain a comprehensive view of the epidemiology of CCPP, a precondition for the development of improved disease surveillance and control measures. PMID- 26149262 TI - Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3 (3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives. AB - BACKGROUND: A new series of 1-aromatic methyl-substituted 3-(3,5 dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. METHODS: A series of new 6-azido and 6-amino derivatives of 1 substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicities of the compounds were evaluated using the viability of mock-infected cells. RESULTS: Some of these compounds showed good-to-moderate activities against HIV-1 with half maximal effective concentration (EC50) values in the submicromolar or subnanomolar range. Compared with emivirine, compound 6-amino-3-(3,5 dimethylbenzyl)-1-(4-aminobenzyl)uracil showed significant anti-HIV-1 activity with an EC50 value of 10 nM and a high selectivity index of 1923. Preliminary structure-activity relationship studies and molecular modeling analyses were carried out to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil; these results may be important for further development of this class of compounds as anti-HIV-1 agents. CONCLUSION: The excellent activity of 6-amino-3-(3,5 dimethylbenzyl)-1-(4-aminobenzyl)uracil (EC50: 0.010 +/- 0.006 uM, SI: >1923) may serve as the basis for conducting further investigations on the behavior of this class of compounds against drug-resistant mutants. PMID- 26149263 TI - Efficacy of N-methanocarbathymidine against genital herpes simplex virus type 2 shedding and infection in guinea pigs. AB - BACKGROUND: Current approved nucleoside therapies for genital herpes simplex virus (HSV) infections are effective but improved therapies are needed for treatment of both acute and recurrent diseases. METHODS: The effects of N methanocarbathymidine were evaluated and compared to acyclovir using guinea pig models of acute and recurrent infection. For acute disease following intravaginal inoculation of 10(6 )pfu HSV-2 (MS strain), animals were treated intraperitoneally beginning 24 h post-infection, and the effects on disease severity, vaginal virus replication, subsequent recurrences, and latent virus loads were evaluated. For evaluation of recurrent infection, animals were treated for 21 days beginning 14 days after infection and disease recurrence and recurrent shedding were evaluated. RESULTS: Treatment of the acute disease with N methanocarbathymidine significantly reduced the severity of acute disease and decreased acute vaginal virus shedding more effectively than acyclovir. Significantly, none of the animals developed visible disease in the high-dose N methanocarbathymidine group and this was the only group in which the number of days with recurrent virus shedding was reduced. Treatment of recurrent disease was equivalent to acyclovir when acyclovir was continuously supplied in the drinking water. CONCLUSION: N-methanocarbathymidine was effective as therapy for acute and recurrent genital HSV-2 disease in the guinea pig models. PMID- 26149264 TI - Identification of a dibenzocyclooctadiene lignan as a HIV-1 non-nucleoside reverse transcriptase inhibitor. AB - BACKGROUND: Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs. METHODS: HIV-1 inhibitors were identified and biologically characterized for mechanism of action. RESULTS: We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 uM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays. CONCLUSIONS: This compound provides a new scaffold for further optimization of activity through structure-guided design. PMID- 26149265 TI - Influence of L-lysine amino acid on the HIV-1 RNA replication in vitro. AB - BACKGROUND: Virus replication strongly depends on host metabolic machinery and essential cellular factors, in particular, on amino acid profiles. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in many metabolic pathways, including gene expression. The inhibitory effects of deficiency or excess of these essential elements on virus replication are widely appreciated. Although the same interrelationship between host cellular factors and HIV have been recognized for a long time, the effects of amino acids on HIV-1 RNA replication dynamic is not yet well documented. Our aim was to determine in this pilot study the direct effect of L-lysine amino acid on HIV-1 RNA replication in vitro in HIV-infected patients. METHODS: A total of 100 HIV-1-infected males without highly active antiretroviral therapy (HAART) were monitored in our center. The patients were in stage A of the disease according to the 1993 Centers for Disease Control (CDC) classification system for HIV-infection. Patients with HIV were enrolled in one stage (A) of the disease with the average amount CD4 lymphocytes in the range of 200-300 cells/uL at the time of sample acquisition. For evaluation of the effects of essential L-lysine amino acid on HIV-1 RNA replication level, we used a model of amino acid-excess system in vitro following incubation of plasma samples for 24 h at 25 degrees C. Quantitative HIV-1 RNA assay was performed using (RT-PCR) reverse-transcriptase polymerase chain reaction (Rotor-Gene Q, QIAGEN, Germany). RESULTS: The mean HIV-1 RNA levels were significantly higher in the enriched peripheral blood mononuclear cells plasma samples HIV-infected subjects after 24 h incubation at 25 degrees C temperature than in the plasma samples the same patients studied on the date of blood tests (p < 0.0001). The number of HIV-1 RNA copies increased in 1.5 times. We observed that in plasma of the same HIV-infected patients after adding L-lysine and following incubation in vitro, viral load increased significantly in comparison with standard samples (p < 0.0001). The increased viral load was found in 100/92 (92%) of HIV-infected subjects. The average number of HIV-1 RNA copies in samples had increased by 4.0 times. However, we found no difference in HIV-1 RNA levels after replacement of L-lysine for L-arginine in comparison samples in the same HIV-infected patients. It is obvious that the addition of L-arginine does not increase viral replication in vitro as L-lysine amino acid supplement does. Additionally, no increase in viral load was determined after adding L-lysine and non toxic doses of its inhibitor (L-lysine alpha-oxidase) in plasma samples. CONCLUSIONS: The results show that L-lysine amino acid excess is characterized by significant increased of HIV-1 RNA copies in enriched peripheral blood mononuclear cells plasma samples of HIV-infected patients. There was evidence for an association between L-lysine supplementation and HIV-1 RNA replication and the level changes of this host essential nutritional element play a key role in the synthesis of the virus proteins and in transcription initiation of the retrovirus life cycle. High intake of L-lysine amino acid may increase the risk of high viral load, subsequent acceleration of immunosuppression and HIV progression. Overall results demonstrate that the simple L-lysine-related model in vitro can be widely used for practical purposes to evaluate HIV-1 RNA replication dynamic, disease prognosis and new approaches in treatment of the patients with human immunodeficiency virus. Although the impact mechanism of L-lysine amino acid on the viral load in the pathogenesis of HIV-infection is at present conjectural and requires further development, the results highlight an interesting target in antiviral therapy, and this statement remains to be proved in further research and clinical trials. PMID- 26149266 TI - Cyclodepsipeptides produced by actinomycetes inhibit cyclic-peptide-mediated quorum sensing in Gram-positive bacteria. AB - Cyclic peptides are commonly used as quorum-sensing autoinducers in Gram-positive Firmicutes bacteria. Well-studied examples of such molecules are thiolactone and lactone, used to regulate the expression of a series of virulence genes in the agr system of Staphylococcus aureus and the fsr system of Enterococcus faecalis, respectively. Three cyclodepsipeptides WS9326A, WS9326B and cochinmicin II/III were identified as a result of screening actinomycetes culture extracts for activity against the agr/fsr system. These molecules are already known as receptor antagonists, the first two for tachykinin and the last one for endothelin. WS9326A also inhibited the transcription of pfoA regulated by the VirSR two-component system in Clostridium perfringens. Receptor-binding assays using a fluorescence-labeled autoinducer (FITC-GBAP) showed that WS9326A and WS9326B act as receptor antagonists in this system. In addition, an ex vivo assay showed that WS9326B substantially attenuated the toxicity of S. aureus for human corneal epithelial cells. These results suggest that these three natural cyclodepsipeptides have therapeutic potential for targeting the cyclic peptide mediated quorum sensing of Gram-positive pathogens. PMID- 26149267 TI - Feasibility of magnetic resonance elastography for the pancreas at 3T. AB - PURPOSE: 1) To assess the usefulness of an elastic belt bracing the upper abdomen for reducing the miscalculated areas of the pancreas on 3.0T magnetic resonance elastography (MRE); 2) to test whether MRE can detect difference of stiffness between normal pancreas and the focal pancreatic diseases. MATERIALS AND METHODS: Using an initial eight normal volunteers, miscalculated areas were compared between MRE with the elastic belt and without the belt on 3.0T MRI. Then, using the belt, MRE of the normal pancreas was measured using 14 volunteers and 11 patients with focal pancreatic lesions. RESULTS: The median (95% confidence interval [CI]) percentages of correctly calculated areas were 57.4% (32.9-63.0) with the elastic belt and 35.3% (11.4-60.4) without the belt (P = 0.0078). The stiffness of each pancreatic segment of the normal volunteers (mean +/- SE) was 2.37 +/- 0.16 kPa for the head, 2.46 +/- 0.17 kPa for the body, and 2.58 +/- 0.26 kPa for the tail. The stiffness of seven pancreatic cancers was 6.06 +/- 0.49 kPa, which was higher than the overall pancreatic stiffness of the normal volunteers (2.47 +/- 0.11 kPa, P < 0.0001). Stiffness of the pancreatic lesions in the head of 6.03 +/- 0.42 kPa, body of 5.57 +/- 0.82 kPa, and tail of 5.9 +/- 1.9 kPa were also higher than those of corresponding segments of the normal volunteers (P = 0.0011, 0.0029, and 0.029, respectively). CONCLUSION: With the elastic belt, miscalculation of the pancreatic stiffness was reduced. MRE showed differences of stiffness between normal pancreas and pancreatic lesions. PMID- 26149268 TI - A [3 + 2]-annulation approach to tetrasubstituted furans from MBH-carbonates of acetylenic aldehydes via sequential substitution/cycloisomerization. AB - A novel metal-free approach to construct the tetrasubstituted furans from Morita Baylis-Hillman (MBH)-carbonates of acetylenic aldehydes has been developed. This strategy involves the cascade nucleophilic substitution/5-exo-dig cycloisomerization of MBH-carbonates with 1,3-dicarbonyl compounds to give uniquely substituted 2-furan-3-yl acrylates. Additionally, the obtained furan adducts open a new entry to naphthofurans through palladium-catalyzed decarboxylative benzannulation. PMID- 26149269 TI - The Association Between Psychopathic Personality Traits and Victimization and Exposure to Violence in a Sample of Saudi Arabian Youth. AB - Psychopathic personality traits have been shown to increase the odds of a wide range of antisocial outcomes. Very little research, however, has examined the association between psychopathy and the risk of personal victimization. The current study address this gap in the literature by examining the association between scores on the Levenson Self-Report Psychopathy scale and a self-reported measure of victimization by using cross-sectional data drawn from a sample of youth residing in Jeddah, Saudi Arabia (N = 311). The results revealed a positive and statistically significant association between LSPR scores and the odds of being victimized. Additional analyses revealed that two mediators-arrest history and exposure to delinquent peers-were related to personal victimization, but neither of these measures mediated the effects of LSPR scores on victimization. Whether these findings would generalize to other nations remains an issue awaiting future research. PMID- 26149270 TI - Molecular Damage in Glaucoma: from Anterior to Posterior Eye Segment. The MicroRNA Role. AB - Glaucoma targets a variety of different tissues located in both anterior (e.g., trabecular meshwork) and posterior (e.g., optic nerve head) ocular segments. The transmission of damage between these structures cannot be simply ascribed to intraocular pressure increase. Recent experimental findings provide evidence for the involvement of molecular mediators including proteins and microRNAs. Aqueous humor protein composition is characteristically altered during glaucoma progression. Immunohistochemistry analyses indicate that proteins characterizing glaucomatous aqueous humor are released by damaged trabecular meshwork. This feature incudes (a) Nestin, involved in stem cell recruitment and glial cell activation; (b) A Kinase anchor protein, released as consequence of mitochondrial damage and Rho activation establishing cell shape and motility; (c) Actin related protein 2/3 complex, involved in actin polymerization and cell shape maintenance. As established both in vitro and in glaucomatous aqueous humor, trabecular meshwork cells damaged by oxidative stress release extracellular microRNAs inducing glial cell activation, an established pathogenic mechanism in neurodegenerative diseases. Released microRNAs include miR-21 (apoptosis), miR 450 (cell aging, maintenance of contractile tone), miR-107 (Nestin expression, apoptosis), miR-149 (endothelia and extracellular matrix homeostasis). Experimental evidences indicate that the uveoscleral pathway, via suprachoroidal space, can provide a potential route of access from the anterior region to the posterior segment of the eye and could represent the path followed by biologic mediators to reach the inner layer of the peripapillary retina and transmit damage signals from the anterior to posterior segment during glaucoma course. PMID- 26149271 TI - Prenatal diagnosis using genetic sequencing and identification of a novel mutation in MMACHC. AB - BACKGROUND: Combined methylmalonic aciduria and homocystinuria, cobalamin(cbl)C deficiency, is a rare disorder of intracellular vitamin B12(cbl) metabolism caused by mutations in the MMACHC gene. Both genetic and biochemical approach have been established to diagnose children and fetuses with cblC deficiency, while in China there is no report of prenatal genetic diagnosis of cblC deficiency. The aim of the present study was to characterize the mutational spectrum of cblC deficiency and investigate the feasibility of genetic-sequencing based prenatal diagnosis for cblC deficiency. METHODS: 10 pedigrees were recruited in this study with the probands clinically and biochemically confirmed combined methymalonic aciduria and homocystinuria. Peripheral blood samples were collected for MMACHC genetic test from the probands and their parents (4 probands had already dead) and 50 control subjects. The entire coding region and adjacent splice sites of MMACHC were sequenced. After the genotypes of the pedigrees were identified, chorionic villi sampling were performed for 3 high-risk pregnant women for prenatal genetic diagnosis. RESULTS: A total of 7 mutations were identified: c.217C > T (R73X), c.394C > T (R132X), c.463G > C (G155R), c.609G > A (W203X), c.616C > T (R206W), c.658-660delAAG (220delK), and c.567dupT (I190YfsX13), as well as 2 polymophsims: c.321G > A(V107V), c.-302G > T. And G155R is a novel mutation that haven't been reported in the literatures. All the 6 probands identified with compound heterozygous mutations or homozygous mutations of MMACHC gene, and all the parents of the probands were found to have one MMACHC mutation at a heterozygous level. Prenatal diagnosis of fetuses from 3 families with a child affected cblC deficiency showed that one fetus had the same compound heterozygous mutations as the proband, one did not have MMACHC mutation, and the third fetus had a mutation at a heterozygous level of MMACHC gene. Results from the follow-ups were consistent with the prenatal diagnosis. CONCLUSION: A novel mutation p.G155R of the MMACHC gene is identified. Genetic diagonsis is an accurate and convenient method for prenatal diagnosis and early intervention of combined methylmalonic aciduria and homocystinuria. PMID- 26149272 TI - Daytime soybean transcriptome fluctuations during water deficit stress. AB - BACKGROUND: Since drought can seriously affect plant growth and development and little is known about how the oscillations of gene expression during the drought stress-acclimation response in soybean is affected, we applied Illumina technology to sequence 36 cDNA libraries synthesized from control and drought stressed soybean plants to verify the dynamic changes in gene expression during a 24-h time course. Cycling variables were measured from the expression data to determine the putative circadian rhythm regulation of gene expression. RESULTS: We identified 4866 genes differentially expressed in soybean plants in response to water deficit. Of these genes, 3715 were differentially expressed during the light period, from which approximately 9.55% were observed in both light and darkness. We found 887 genes that were either up- or down-regulated in different periods of the day. Of 54,175 predicted soybean genes, 35.52% exhibited expression oscillations in a 24 h period. This number increased to 39.23% when plants were submitted to water deficit. Major differences in gene expression were observed in the control plants from late day (ZT16) until predawn (ZT20) periods, indicating that gene expression oscillates during the course of 24 h in normal development. Under water deficit, dissimilarity increased in all time-periods, indicating that the applied stress influenced gene expression. Such differences in plants under stress were primarily observed in ZT0 (early morning) to ZT8 (late day) and also from ZT4 to ZT12. Stress-related pathways were triggered in response to water deficit primarily during midday, when more genes were up regulated compared to early morning. Additionally, genes known to be involved in secondary metabolism and hormone signaling were also expressed in the dark period. CONCLUSIONS: Gene expression networks can be dynamically shaped to acclimate plant metabolism under environmental stressful conditions. We have identified putative cycling genes that are expressed in soybean leaves under normal developmental conditions and genes whose expression oscillates under conditions of water deficit. These results suggest that time of day, as well as light and temperature oscillations that occur considerably affect the regulation of water deficit stress response in soybean plants. PMID- 26149273 TI - Interactome analysis brings splicing into focus. AB - The spliceosome is a huge molecular machine that assembles dynamically onto its pre-mRNA substrates. A new study based on interactome analysis provides clues about how splicing-regulatory proteins modulate assembly of the spliceosome to either activate or repress splicing.Please see related Research article: http://www.genomebiology.com/2015/16/1/119/abstract. PMID- 26149274 TI - The importance of reliable information exchange in emergency practices: a misunderstanding that was uncovered before it was too late. AB - BACKGROUND: Many medical emergency practices are regulated by written procedures that normally provide reliable guidelines for action. In some cases, however, the consequences of following rule-based instructions can have unintended negative consequences. The article discusses a case - described on a type level - where the consequences of following a rule formulation could have been fatal. CASE PRESENTATION: A weak and elderly patient has cardiac arrest, and a Do Not Resuscitate (DNR) clause is written in the patient's medical record. Paramedics at the scene cannot see that the patient's general appearance match conditions which would indicate the DNR clause, so they start cardiopulmonary resuscitation (CPR), and the patient survives. This turns out to be a crucial decision. The DNR clause is from an earlier bout with serious disease from which the patient has recovered, against all odds, and someone has forgotten to remove the clause from the medical record. ANALYSIS: In order to be able to interpret the validity of written guidelines, paramedics and other health workers need to develop personal skills that transcend the ability simply to follow written instructions. Within traditional virtue ethics, personal judgment is conceived of as crucial for being able to make 'good' autonomous decisions. Virtue ethical analyses, decision making abilities and non-technical communication skills are important as conceptual tools when health workers need to make difficult clinical decisions. CONCLUSION: The case study accentuates the significance of prudent judgment in medical practice. In the case described, the consequence of trusting the written advance directive could have been fatal, but the point is general: for the purpose of achieving excellent organizational performance, it is insufficient for health workers to rely uncritically on rules and procedures. Even the clearest rule formulations must be interpreted contextually in order to determine ethically correct behavior and avoid potential negative consequences that are not in the patient's best interests. PMID- 26149275 TI - The clinical and cost effectiveness of group art therapy for people with non psychotic mental health disorders: a systematic review and cost-effectiveness analysis. AB - BACKGROUND: The majority of mental health problems are non-psychotic (e.g., depression, anxiety, and phobias). For some people, art therapy may be a more acceptable alternative form of psychological therapy than standard forms of treatment, such as talking therapies. This study was part of a health technology assessment commissioned by the National Institute for Health Research, UK and aimed to systematically appraise the clinical and cost-effective evidence for art therapy for people with non-psychotic mental health disorders. METHODS: Comprehensive literature searches for studies examining art therapy in populations with non-psychotic mental health disorders were performed in May 2013. A quantitative systematic review of clinical effectiveness and a systematic review of studies evaluating the cost-effectiveness of group art therapy were conducted. RESULTS: Eleven randomised controlled trials were included (533 patients). Meta-analysis was not possible due to clinical heterogeneity and insufficient comparable data on outcome measures across studies. The control groups varied between studies but included: no treatment/wait-list, attention placebo controls and psychological therapy comparators. Art therapy was associated with significant positive changes relative to the control group in mental health symptoms in 7 of the 11 studies. A de novo model was constructed and populated with data identified from the clinical review. Scenario analyses were conducted allowing comparisons of group art therapy with wait-list control and group art therapy with group verbal therapy. Group art-therapy appeared cost effective compared with wait-list control with high certainty although generalisability to the target population was unclear; group verbal therapy appeared more cost-effective than art therapy but there was considerable uncertainty and a sizeable probability that art therapy was more cost effective. CONCLUSIONS: From the limited available evidence art therapy was associated with positive effects compared with control in a number of studies in patients with different clinical profiles. The included trials were generally of poor quality and are therefore likely to be at high risk of bias. Art therapy appeared to be cost-effective versus wait-list but further studies are needed to confirm this finding in the target population. There was insufficient evidence to make an informed comparison of the cost-effectiveness of group art therapy with group verbal therapy. TRIAL REGISTRATION: HTA project no. 12/27/16; PROSPERO registration no. CRD42013003957. PMID- 26149276 TI - Much ado about omics: welcome to 'the permutome'. PMID- 26149277 TI - Cold acclimation affects immune composition in skeletal muscle of healthy lean subjects. AB - Low environmental temperatures have a profound effect on biological processes in the body, including the immune system. Cold exposure coincides with hormonal changes, which may directly or indirectly alter the immune system, even in the skeletal muscle. The aim of the present study was to investigate the effect of cold acclimation on immune composition in skeletal muscle. Skeletal muscle biopsies were obtained from 17 healthy lean subjects before and after 10 days of mild cold exposure (15 degrees : C, 6 h/day). Nonshivering thermogenesis was calculated by indirect calorimetry. We found that cold acclimation increased nonshivering thermogenesis from 10.8 +/- 7.5 before to 17.8 +/- 11.1% after cold acclimation (P < 0.01), but did not affect plasma catecholamine nor cytokine levels. In contrast, cold acclimation affected mRNA expression of several immune cell markers in skeletal muscle. It downregulated expression of the Th17 markers RORC (-28%, P < 0.01) and NEDD4L (-15%, P < 0.05), as well as the regulatory T cell marker FOXP3 (-13%, P < 0.05). Furthermore, cold acclimation downregulated expression of the M2 macrophage markers CCL22 (-50%, P < 0.05), CXCL13 (-17%, P < 0.05) and CD209 (-15%, P < 0.05), while the M1 macrophage marker IL12B was upregulated (+141%, P < 0.05). Cold acclimation also enhanced several markers related to interferon (IFN) signaling, including TAP1 (+12%, P < 0.01), IFITM1/3 (+11%, P < 0.05), CD274 (+36%, P < 0.05) and STAT 2 (+10%, P < 0.05). In conclusion, 10 days of intermittent cold exposure induces marked changes in the expression of immune cell markers in skeletal muscle of healthy lean subjects. The physiological consequences and therapeutic relevance of these changes remain to be determined. PMID- 26149278 TI - Internal comparison between deuterium oxide (D2O) and L-[ring-13C6] phenylalanine for acute measurement of muscle protein synthesis in humans. AB - Stable isotope tracer methodologies are becoming increasingly widespread in metabolic research; yet a number of factors restrict their implementation, such as, i.v infusions, multiple cannulae, tissue samples, and significant cost. We recently validated the sensitivity of the orally administered stable isotope tracer deuterium oxide (D2O) for quantifying day-to-day changes in muscle protein synthesis (MPS). This method is less invasive, restrictive, and more cost effective than traditional amino acid (AA) tracer techniques. In the present study, we hypothesized the sensitivity of our analytical techniques (GC-Pyrolysis IRMS) would permit D2O-derived measurements of MPS over much shorter periods (i.e., hours) usually only possible using AA-tracer techniques. We recruited nine males (24 +/- 3 year, BMI: 25 +/- 3 kg.m(-)2) into an internally controlled comparison of D2O versus (13)C AA-tracers. The day before the acute study subjects consumed 400 mL D2O, and on the study day, received a primed (0.3 mg.kg( 1)) continuous (0.6 mg.kg.h(-1)) i.v infusion of L-[ring-(13)C6]-phenylalanine to quantify MPS under both: (1) basal [postabsorptive] and; (2) stimulated [postprandial] that is, consumption of 20 g EAA, conditions. Measures of MPS yielded indistinguishable technique differences with respect to EAA, (13)C: 0.065 +/- 0.004 to 0.089 +/- 0.006%.h(-1) (P < 0.05) and D2O: 0.050 +/- 0.007 to 0.088 +/- 0.008%.h(-1) (P < 0.05) with qualitatively similar increases. Our findings reveal that acute measurement of MPS, usually only possible using AA-tracers, are feasible over shorter periods with orally administered D2O when used in tandem with GC-Pyrolysis-IRMS. We conclude that this D2O approach provides a less invasive, cost-effective, and flexible means by which to quantify MPS acutely over several hours. PMID- 26149279 TI - Gender differences in response to acute and chronic angiotensin II infusion: a translational approach. AB - Women with renal disease progress at a slower rate to end stage renal disease than men. As angiotensin II has both hemodynamic and direct renal effects, we hypothesized that the female protection may result from gender differences in responses to angiotensin II. Therefore, we studied gender differences in response to angiotensin II, during acute (human) and chronic (rats) angiotensin II administration. In young healthy men (n = 18) and women (n = 18) we studied the responses of renal hemodynamics ((125)I-iothalamate and (131)I-Hippuran) and blood pressure to graded angiotensin II infusion (0.3, 1.0, and 3.0 ng/kg/min for 1 h). Men had increased responses of diastolic blood pressure (P = 0.01), mean arterial pressure (P = 0.05), and a more pronounced decrease in effective renal plasma flow (P = 0.009) than women. We measured the changes in proteinuria and blood pressure in response to chronic administration (200 ng/kg/min for 3 weeks) of angiotensin II in rats. Male rats had an increased response of proteinuria compared with females (GEE analysis, P = 0.001). Male, but not female, angiotensin II-treated rats had increased numbers of renal interstitial macrophages compared to sham-treated rats (P < 0.001). In conclusion, gender differences are present in the response to acute and chronic infusion of angiotensin II. Difference in angiotensin II sensitivity could play a role in gender differences in progression of renal disease. PMID- 26149280 TI - Adaptive shut-down of EEG activity predicts critical acidemia in the near-term ovine fetus. AB - In fetal sheep, the electrocorticogram (ECOG) recorded directly from the cortex during repetitive heart rate (FHR) decelerations induced by umbilical cord occlusions (UCO) predictably correlates with worsening hypoxic-acidemia. In human fetal monitoring during labor, the equivalent electroencephalogram (EEG) can be recorded noninvasively from the scalp. We tested the hypothesis that combined fetal EEG - FHR monitoring allows for early detection of worsening hypoxic acidemia similar to that shown for ECOG-FHR monitoring. Near-term fetal sheep (n = 9) were chronically instrumented with arterial and venous catheters, ECG, ECOG, and EEG electrodes and umbilical cord occluder, followed by 4 days of recovery. Repetitive UCOs of 1 min duration and increasing strength (with regard to the degree of reduction in umbilical blood flow) were induced each 2.5 min until pH dropped to <7.00. Repetitive UCOs led to marked acidosis (arterial pH 7.35 +/- 0.01 to 7.00 +/- 0.03). At pH of 7.22 +/- 0.03 (range 7.32-7.07), and 45 +/- 9 min (range 1 h 33 min-20 min) prior to attaining pH < 7.00, both ECOG and EEG amplitudes began to decrease ~fourfold during each FHR deceleration in a synchronized manner. Confirming our hypothesis, these findings support fetal EEG as a useful adjunct to FHR monitoring during human labor for early detection of incipient fetal acidemia. PMID- 26149281 TI - Blood flow restriction prevents muscle damage but not protein synthesis signaling following eccentric contractions. AB - There is a growing body of evidence to suggest that resistance training exercise combined with blood flow restriction (BFR) increases muscle size and strength in humans. Eccentric contraction (ECC) frequently induces severe muscle damage. However, it is not known whether and to what extent muscle damage occurs following ECC + BFR due to the difficulty of conducting definitive invasive studies. The purpose of this study was to examine muscle fiber damage following ECC + BFR at the cellular level. High-intensity ECC was purposefully selected to maximize the opportunity for muscle damage and hypertrophic signaling in our novel in vivo animal model. Male Wistar rats were assigned randomly to the following groups: ECC and ECC + BFR at varying levels of occlusion pressure (140, 160, and 200 Torr). In all conditions, electrical stimulation was applied to the dorsiflexor muscles simultaneously with electromotor-induced plantar flexion. We observed severe histochemical muscle fiber damage (area of damaged fibers/total fiber area analyzed) following ECC (26.4 +/- 4.0%). Surprisingly, however, muscle damage was negligible following ECC + BFR140 (2.6 +/- 1.2%), ECC+BFR160 (3.0 +/- 0.5%), and ECC + BFR200 (0.2 +/- 0.1%). Ribosomal S6 kinase 1 (S6K1) phosphorylation, a downstream target of rapamycin (mTOR)-phosphorylation kinase, increased following ECC + BFR200 as well as ECC. In contrast, S6K1 phosphorylation was not altered by BFR alone. The present findings suggest that ECC combined with BFR, even at high exercise intensities, may enhance muscle protein synthesis without appreciable muscle fiber damage. PMID- 26149282 TI - Cerebrovascular regulation in men and women: stimulus-specific role of cyclooxygenase. AB - Greater cerebral artery vasodilation mediated by cyclooxygenase (COX) in female animals is unexplored in humans. We hypothesized that young, healthy women would exhibit greater basal cerebral blood flow (CBF) and greater vasodilation during hypoxia or hypercapnia compared to men, mediated by a larger contribution of COX. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 42 adults (24 women, 18 men; 24 +/- 1 years) during two visits, in a double-blind, placebo-controlled design (COX inhibition, 100 mg oral indomethacin, Indo). Women were studied early in the follicular phase of the menstrual cycle (days 1-5). Two levels of isocapnic hypoxia (SPO2 = 90% and 80%) were induced for 5-min each. Separately, hypercapnia was induced by increasing end-tidal carbon dioxide (PETCO 2) 10 mmHg above baseline. A positive change in MCAv (DeltaMCAv) reflected vasodilation. Basal MCAv was greater in women compared to men (P < 0.01) across all conditions. Indo decreased baseline MCAv (P < 0.01) similarly between sexes. Hypoxia increased MCAv (P < 0.01), but DeltaMCAv was not different between sexes. Indo did not alter hypoxic vasodilation in either sex. Hypercapnia increased MCAv (P < 0.01), but DeltaMCAv was not different between sexes. Indo elicited a large decrease in hypercapnic vasodilation (P < 0.01) that was similar between sexes. During the early follicular phase, women exhibit greater basal CBF than men, but similar vasodilatory responses to hypoxia and hypercapnia. Moreover, COX is not obligatory for hypoxic vasodilation, but plays a vital and similar role in the regulation of basal CBF (~30%) and hypercapnic response (~55%) between sexes. PMID- 26149283 TI - Standing balance in individuals with Parkinson's disease during single and dual task conditions. AB - This study aimed to examine the differences in standing balance between individuals with Parkinson's disease (PD) and subjects without PD (control group), under single and dual-task conditions. A cross-sectional study was designed using a non-probabilistic sample of 110 individuals (50 participants with PD and 60 controls) aged 50 years old and over. The individuals with PD were in the early or middle stages of the disease (characterized by Hoehn and Yahr as stages 1-3). The standing balance was assessed by measuring the centre of pressure (CoP) displacement in single-task (eyes-open/eyes-closed) and dual-task (while performing two different verbal fluency tasks). No significant differences were found between the groups regarding sociodemographic variables. In general, the standing balance of the individuals with PD was worse than the controls, as the CoP displacement across tasks was significantly higher for the individuals with PD (p<0.01), both in anteroposterior and mediolateral directions. Moreover, there were significant differences in the CoP displacement based parameters between the conditions, mainly between the eyes-open condition and the remaining conditions. However, there was no significant interaction found between group and condition, which suggests that changes in the CoP displacement between tasks were not influenced by having PD. In conclusion, this study shows that, although individuals with PD had a worse overall standing balance than individuals without the disease, the impact of performing an additional task on the CoP displacement is similar for both groups. PMID- 26149284 TI - Advances in salivary gland gene therapy - oral and systemic implications. AB - INTRODUCTION: Much research demonstrates the feasibility and efficacy of gene transfer to salivary glands. Recently, the first clinical trial targeting a salivary gland was completed, yielding positive safety and efficacy results. AREAS COVERED: There are two major disorders affecting salivary glands: radiation damage following treatment for head and neck cancers and Sjogren's syndrome (SS). Salivary gland gene transfer has also been employed in preclinical studies using transgenic secretory proteins for exocrine (upper gastrointestinal tract) and endocrine (systemic) applications. EXPERT OPINION: Salivary gland gene transfer is safe and can be beneficial in humans. Applications to treat and prevent radiation damage show considerable promise. A first-in-human clinical trial for the former was recently successfully completed. Studies on SS suffer from an inadequate understanding of its etiology. Proof of concept in animal models has been shown for exocrine and endocrine disorders. Currently, the most promising exocrine application is for the management of obesity. Endocrine applications are limited, as it is currently impossible to predict if systemically required transgenic proteins will be efficiently secreted into the bloodstream. This results from not understanding how secretory proteins are sorted. Future studies will likely employ ultrasound-assisted and pseudotyped adeno-associated viral vector-mediated gene transfer. PMID- 26149286 TI - The Role of Micelle Size in Tumor Accumulation, Penetration, and Treatment. AB - The specific sizes that determine optimal nanoparticle tumor accumulation, penetration, and treatment remain inconclusive because many studies compared nanoparticles with multiple physicochemical variables (e.g., chemical structures, shapes, and other physical properties) in addition to the size. In this study, we synthesized amphiphilic block copolymers of 7-ethyl-10-hydroxylcamptothecin (SN38) prodrug and fabricated micelles with sizes ranging from 20 to 300 nm from a single copolymer. The as-prepared micelles had exactly the same chemical structures and similar physical properties except for size, which provided an ideal platform for a systematic investigation of the size effects in cancer drug delivery. We found that the micelle's blood circulation time and tumor accumulation increased with the increase in their diameters, with optimal diameter range of 100 to 160 nm. However, the much higher tumor accumulation of the large micelles (100 nm) did not result in significantly improved therapeutic efficacy, because the large micelles had poorer tumor penetration than the small ones (30 nm). An optimal size that balances drug accumulation and penetration in tumors is critical for improving the therapeutic efficacy of nanoparticulate drugs. PMID- 26149287 TI - Woman with learning difficulties is awarded L65,000 after "appalling" treatment by hospital. PMID- 26149285 TI - Redox-sensitive transient receptor potential channels in oxygen sensing and adaptation. AB - Regulation of ion channels is central to the mechanisms that underlie immediate acute physiological responses to changes in the availability of molecular oxygen (O2). A group of cation-permeable channels that are formed by transient receptor potential (TRP) proteins have been characterized as exquisite sensors of redox reactive species and as efficient actuators of electric/ionic signals in vivo. In this review, we first discuss how redox-sensitive TRP channels such as TRPA1 have recently emerged as sensors of the relatively inert oxidant O2. With regard to the physiological significance of O2 sensor TRP channels, vagal TRPA1 channels are mainly discussed with respect to their role in respiratory regulation in comparison with canonical pathways in glomus cells of the carotid body, which is a well-established O2-sensing organ. TRPM7 channels are discussed regarding hypoxia-sensing function in ischemic cell death. Also, ubiquitous expression of TRPA1 and TRPM7 together with their physiological relevance in the body is examined. Finally, based upon these studies on TRP channels, we propose a hypothesis of "O2 remodeling." The hypothesis is that cells detect deviation of O2 availability from appropriate levels via sensors and adjust local O2 environments in vivo by controlling supply and consumption of O2 via pathways comprising cellular signals and transcription factors downstream of sensors, which consequently optimize physiological functions. This new insight into O2 adaptation through ion channels, particularly TRPs, may foster a paradigm shift in our understanding in the biological significance of O2. PMID- 26149288 TI - Study of laser uncaging induced morphological alteration of rat cortical neurites using atomic force microscopy. AB - Activity-dependent structural remodeling is an important aspect of neuronal plasticity. In the previous researches, neuronal structure variations resulting from external interventions were detected by the imaging instruments such as the fluorescence microscopy, the scanning/transmission electron microscopy (SEM/TEM) and the laser confocal microscopy. In this article, a new platform which combined the photochemical stimulation with atomic force microscopy (AFM) was set up to detect the activity-dependent structural remodeling. In the experiments, the cortical neurites on the glass coverslips were stimulated by locally uncaged glutamate under the ultraviolet (UV) laser pulses, and a calcium-related structural collapse of neurites (about 250 nm height decrease) was observed by an AFM. This was the first attempt to combine the laser uncaging with AFM in living cell researches. With the advantages of highly localized stimulation (<5 MUm), super resolution imaging (<3.8 nm), and convenient platform building, this system was suitable for the quantitative observation of the neuron mechanical property variations and morphological alterations modified by neural activities under different photochemical stimulations, which would be helpful for studying physiological and pathological mechanisms of structural and functional changes induced by the biomolecule acting. PMID- 26149289 TI - The use of a cerebral perfusion and immersion-fixation process for subsequent white matter dissection. AB - BACKGROUND: The Klingler's method for white matter dissection revolutionized the study of deep cerebral anatomy. Although this technique made white matter dissection more feasible and widely used, it still presents some intrinsic limitations. NEW METHOD: We evaluated the quality of different methods for specimen preparation based on an intra-carotidal formalin perfusion fixation process. Ten post-mortem human hemispheres were prepared with this method and dissected in a stepwise manner. RESULTS: The homogeneous and rapid fixation of the brain allowed documentation of several fine additional anatomical details. Intra-cortical white matter terminations were described during the first stage of dissection on each specimen. No limitations were encountered during dissection of the major associative bundles. On the contrary, the quality of the fixation of the specimens made it possible to isolate them en bloc. One of the most complex and deep bundles (accumbo-frontal fasciculus) was dissected without technical limitations. Deep vascular structures were very well preserved and dissected within the white matter until their sub-millimetric terminations. COMPARISON WITH EXISTING METHOD: Short time for preparation, a more homogeneous fixation, no technical limitation for a detailed description of superficial and deep white matter anatomy, the possibility to dissect with a single technique the fibre organization and the white matter vascular architecture are the advantages reported with the perfusion fixation. CONCLUSION: These results provide encouraging data about the possibility to use a perfusion fixation process, which may help in improving the quality of white matter dissection for research, didactic purposes and surgical training. PMID- 26149290 TI - Interconnecting Carbon Fibers with the In-situ Electrochemically Exfoliated Graphene as Advanced Binder-free Electrode Materials for Flexible Supercapacitor. AB - Flexible energy storage devices are highly demanded for various applications. Carbon cloth (CC) woven by carbon fibers (CFs) is typically used as electrode or current collector for flexible devices. The low surface area of CC and the presence of big gaps (ca. micro-size) between individual CFs lead to poor performance. Herein, we interconnect individual CFs through the in-situ exfoliated graphene with high surface area by the electrochemical intercalation method. The interconnected CFs are used as both current collector and electrode materials for flexible supercapacitors, in which the in-situ exfoliated graphene act as active materials and conductive "binders". The in-situ electrochemical intercalation technique ensures the low contact resistance between electrode (graphene) and current collector (carbon cloth) with enhanced conductivity. The as-prepared electrode materials show significantly improved performance for flexible supercapacitors. PMID- 26149292 TI - An optimization solution of a laser plane in vision measurement with the distance object between global origin and calibration points. AB - Equation construction of a laser plane demonstrates a remarkable importance for vision measurement systems based on the structured light. Here we create a simple 1D target with a cone at the bottom and a checkered pattern on the top to calibrate the equation of the laser plane in the view field of a camera. A group of 2D coordinates of the intersection points are extracted from the images with the 1D target at different positions. The objective function is constructed to optimize the coefficients of the laser plane by minimizing the difference between the distance from the feature point to the the origin point and the length of the 1D target. The projective lines of the optimized laser plane on the 3D calibration board overlap the real intersection lines in the experimental images. Finally, the comparison work about the influences of the non-Gaussian noise and point number is investigated experimentally. The experiments show that the method of the distance optimal object from the feature point to the origin point provides an accurate and robust calibration for the laser plane in structured light measurement. PMID- 26149291 TI - Multimodal data and machine learning for surgery outcome prediction in complicated cases of mesial temporal lobe epilepsy. AB - BACKGROUND: This study sought to predict postsurgical seizure freedom from pre operative diagnostic test results and clinical information using a rapid automated approach, based on supervised learning methods in patients with drug resistant focal seizures suspected to begin in temporal lobe. METHOD: We applied machine learning, specifically a combination of mutual information-based feature selection and supervised learning classifiers on multimodal data, to predict surgery outcome retrospectively in 20 presurgical patients (13 female; mean age+/ SD, in years 33+/-9.7 for females, and 35.3+/-9.4 for males) who were diagnosed with mesial temporal lobe epilepsy (MTLE) and subsequently underwent standard anteromesial temporal lobectomy. The main advantage of the present work over previous studies is the inclusion of the extent of ipsilateral neocortical gray matter atrophy and spatiotemporal properties of depth electrode-recorded seizures as training features for individual patient surgery planning. RESULTS: A maximum relevance minimum redundancy (mRMR) feature selector identified the following features as the most informative predictors of postsurgical seizure freedom in this study's sample of patients: family history of epilepsy, ictal EEG onset pattern (positive correlation with seizure freedom), MRI-based gray matter thickness reduction in the hemisphere ipsilateral to seizure onset, proportion of seizures that first appeared in ipsilateral amygdala to total seizures, age, epilepsy duration, delay in the spread of ipsilateral ictal discharges from site of onset, gender, and number of electrode contacts at seizure onset (negative correlation with seizure freedom). Using these features in combination with a least square support vector machine (LS-SVM) classifier compared to other commonly used classifiers resulted in very high surgical outcome prediction accuracy (95%). CONCLUSIONS: Supervised machine learning using multimodal compared to unimodal data accurately predicted postsurgical outcome in patients with atypical MTLE. PMID- 26149294 TI - Race-specific features and outcomes of nodular lymphocyte-predominant Hodgkin lymphoma: Analysis of the National Cancer Data Base. AB - BACKGROUND: The incidence of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is higher among African Americans than among other races, but to the authors' knowledge, the characteristics of NLPHL in this population have not been evaluated. The authors compared clinical features, treatments, and survival of black and white patients with NLPHL using the National Cancer Data Base. METHODS: The authors extracted the records of 602 black and 1950 white patients with NLPHL who were diagnosed between 1998 and 2011. Overall survival (OS) was compared using the log-rank test. RESULTS: Black patients were on average younger than white patients (median age, 42 years vs 45 years; P =.0001), more often female (49% vs 29%; P<.0001), and more likely to have the axillary lymph nodes as the primary disease site (25% vs 17%; P =.0002). They also had unfavorable socioeconomic characteristics, a higher rate of no treatment in patients with early-stage disease, and a longer time to therapy initiation (median, 53.5 days vs 47 days; P<.0001). Despite this, the authors found no significant difference between the races with regard to stage distribution or survival (P =.39). OS at 7 years was 90.1% in patients with early-stage (American Joint Committee on Cancer stage IA/B, IIA) and 79.4% in patients with advanced stage (American Joint Committee on Cancer stage IIB, III/IV) NLPHL. Survival in the early stage of disease was not found to be significantly different after various treatment strategies (stratified log-rank P = .18), except that the administration of chemotherapy was associated with a better outcome in black patients (log-rank P =.011 vs P =.81 for white patients). CONCLUSIONS: Differences in clinical presentation suggest the interaction of race-specific and sex-specific susceptibility factors for NLPHL. Further research is needed to elucidate these factors, and to investigate possible heterogeneous effects of treatments by race. Clinical trials comparing standard treatment strategies are unlikely to detect differences in OS among patients with early-stage NLPHL. PMID- 26149293 TI - An Intravaginal Ring for the Simultaneous Delivery of an HIV-1 Maturation Inhibitor and Reverse-Transcriptase Inhibitor for Prophylaxis of HIV Transmission. AB - Nucleocapsid 7 (NCp7) inhibitors have been investigated extensively for their role in impeding the function of HIV-1 replication machinery and their ability to directly inactivate the virus. A class of NCp7 zinc finger inhibitors, S-acyl-2 mercaptobenzamide thioesters (SAMTs), was investigated for topical drug delivery. SAMTs are inherently unstable because of their hydrolytically labile thioester bond, thus requiring formulation approaches that can lend stability. We describe the delivery of N-[2-(3,4,5-trimethoxybenzoylthio)benzoyl]-beta-alaninamide (SAMT 10), as a single agent antiretroviral (ARV) therapeutic and in combination with the HIV-1 reverse-transcriptase inhibitor pyrimidinedione IQP-0528, from a hydrophobic polyether urethane (PEU) intravaginal ring (IVR) for a month. The physicochemical stability of the ARV-loaded IVRs was confirmed after 3 months at 40 degrees C/75% relative humidity. In vitro, 25 +/- 3 mg/IVR of SAMT-10 and 86 +/- 13 mg/IVR of IQP-0528 were released. No degradation of the hydrolytically labile SAMT-10 was observed within the matrix. The combination of ARVs had synergistic antiviral activity when tested in in vitro cell-based assays. Toxicological evaluations performed on an organotypic EpiVaginal(TM) tissue model demonstrated a lack of formulation toxicity. Overall, SAMT-10 and IQP-0528 were formulated in a stable PEU IVR for sustained release. Our findings support the need for further preclinical evaluation. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3426-3439, 2015. PMID- 26149295 TI - Field-assisted self-assembly process: general discussion. PMID- 26149297 TI - Post-operative steroid treatment for eosinophilic-type sinonasal polyposis. AB - CONCLUSIONS: The preliminary finding of significantly lower eosinophilic-type CRSwNP recurrence rates in patients with associated asthma or ASA intolerance treated post-operatively with local nasal and oral steroids warrants further investigation in larger, prospective series. OBJECTIVE: A high recurrence rate after functional endoscopic sinus surgery (FESS) has been widely reported in patients with eosinophilic-type chronic rhinosinusitis with nasal polyps (CRSwNP). This study compared the influence of two post-operative medical treatments - local nasal steroids alone vs local nasal and oral steroids - on the recurrence of eosinophilic-type CRSwNP. METHOD: Between January 2009-December 2010, 32 patients with eosinophilic-type CRSwNP received local steroid nasal therapy after FESS (Group A); from January 2011 onwards, another 28 patients were treated post-operatively with the same nasal treatment plus two cycles a year of oral steroids (Group B). All patients in both groups had a follow-up of at least 36 months. RESULTS: Groups A and B did not differ significantly in recurrence rate (31.25% vs 32.14%, p = 1) or disease-free interval (p = 0.91), but Group B patients who were asthmatic or ASA-intolerant had a significantly lower recurrence rate than Group A patients with asthma or ASA intolerance (p = 0.04 and p = 0.004, respectively). PMID- 26149296 TI - Potential application of miRNAs as diagnostic and therapeutic tools in chronic pancreatitis. AB - Chronic pancreatitis (CP) is a progressive inflammatory disease typified by end stage fibrosis. This disease can also increase the risk of pancreatic cancer. The associated diagnosis, pain and other complications further add to the burden of disease management. In recent years, significant progress has been achieved in identifying miRNAs and their physiological functions, including mRNA repression and protein expression control. Given the extensive effort made on miRNA research, a close correlation has been discovered between certain types of miRNAs and disease progression, particularly for tissue fibrosis. Designing miRNA related tools for disease diagnosis and therapeutic treatments presents a novel and potential research frontier. In the current review, we discuss various miRNAs closely interacting with CP, as well as the possible development of targeted miRNA therapies in managing this disease. PMID- 26149298 TI - Is sedation safe and beneficial in patients receiving NIV? No. PMID- 26149299 TI - Early goal-directed therapy in the treatment of sepsis: the times have changed but not the therapy and benefit to patients. PMID- 26149300 TI - Is sedation safe and beneficial in patients receiving NIV? Yes. PMID- 26149301 TI - Early goal-directed therapy in the treatment of sepsis: response to comments by Jaehne et al. PMID- 26149303 TI - Should red blood cell transfusion be individualized? No. PMID- 26149302 TI - Respective impact of no escalation of treatment, withholding and withdrawal of life-sustaining treatment on ICU patients' prognosis: a multicenter study of the Outcomerea Research Group. AB - PURPOSE: To assess the prevalence of decisions to forgo life-sustaining treatment (DFLST), the patients characteristics, and to estimate the impact of DFLST stages on mortality. METHODS: Observational study of a prospective database between 2005 and 2012 from 13 ICUs. DFLST were defined as follows: no escalation of treatment (stage 1), not to start or escalate treatment even if such treatment is considered in the future; withholding (stage 2), not to start or escalate necessary treatment; withdrawal (stage 3), to stop necessary treatment. The impact of daily DFLST stage on day-30 hospital mortality was tested with a discrete-time Cox's model and adjusted for admission severity and daily SOFA score. RESULTS: Of 10,080 patients, 1290 (13%) made DFLST. The highest DFLST stage during the ICU stay was no escalation of treatment in 339 (26%) patients, withholding in 502 (39%) patients, and withdrawal in 449 (35%) patients. Older patients, patients with at least one chronic disease, and patients with greater ICU severity were significantly more numerous in the DFLST group. Day-30 mortality was 13% for non-DFLST patients, 35% for no escalation of treatment, 75% for withholding, 93% for withdrawal. After adjustment, an increase in day-30 mortality was associated with withholding and withdrawal (hazard ratio 95% CI 5.93 [4.95-7.12] and 20.05 [15.58-25.79], P < 0.0001), but not with no escalation of treatment (HR 1.14 [0.91-1.44], P = 0.25). CONCLUSIONS: DFLST were made in 13% of ICU patients. Withholding, withdrawal, older age, more comorbidities, and higher severity of illness were associated with higher mortality. No escalation of treatment was not associated with increased mortality. PMID- 26149304 TI - Should red cell transfusion be individualized? Yes. PMID- 26149306 TI - School Gardens Enhance Academic Performance and Dietary Outcomes in Children. AB - BACKGROUND: Schools face increasing demands to provide education on healthy living and improve core academic performance. Although these appear to be competing concerns, they may interact beneficially. This article focuses on school garden programs and their effects on students' academic and dietary outcomes. METHODS: Database searches in CABI, Web of Science, Web of Knowledge, PubMed, Education Full Text, Education Resources Information Center (ERIC), and PsychINFO were conducted through May 2013 for peer-reviewed literature related to school-day garden interventions with measures of dietary and/or academic outcomes. RESULTS: Among 12 identified garden studies with dietary measures, all showed increases/improvements in predictors of fruit and vegetable (FV) consumption. Seven of these also included self-reported FV intake with 5 showing an increase and 2 showing no change. Four additional interventions that included a garden component measured academic outcomes; of these, 2 showed improvements in science achievement and 1 measured and showed improvements in math scores. CONCLUSIONS: This small set of studies offers evidence that garden-based learning does not negatively impact academic performance or FV consumption and may favorably impact both. Additional studies with more robust experimental designs and outcome measures are necessary to understand the effects of experiential garden-based learning on children's academic and dietary outcomes. PMID- 26149305 TI - Examination of Substance Use, Risk Factors, and Protective Factors on Student Academic Test Score Performance. AB - BACKGROUND: School administrators and teachers face difficult decisions about how best to use school resources to meet academic achievement goals. Many are hesitant to adopt prevention curricula that are not focused directly on academic achievement. Yet, some have hypothesized that prevention curricula can remove barriers to learning and, thus, promote achievement. We examined relationships among school levels of student substance use and risk and protective factors that predict adolescent problem behaviors and achievement test performance. METHODS: Hierarchical generalized linear models were used to predict associations involving school-averaged levels of substance use and risk and protective factors and students' likelihood of meeting achievement test standards on the Washington Assessment of Student Learning, statistically controlling for demographic and economic factors known to be associated with achievement. RESULTS: Levels of substance use and risk/protective factors predicted the academic test score performance of students. Many of these effects remained significant even after controlling for model covariates. CONCLUSIONS: Implementing prevention programs that target empirically identified risk and protective factors has the potential to have a favorable effect on students' academic achievement. PMID- 26149307 TI - The Association Between Asthma and Sleep in Urban Adolescents With Undiagnosed Asthma. AB - BACKGROUND: We examined associations between asthma and sleep in a sample of inner-city adolescents with asthma-like symptoms who are undiagnosed, and to assess the extent to which youth's report of perceived stress moderates this association. METHODS: A total of 349 adolescents (83% girls), with a mean age of 15.8 years, and their primary caregivers participated. Large segments of the sample were Latinos (46%) or African Americans (37%). Adolescents reported on asthma-namely, rate of waking up at night due to asthma-like symptoms and perceived severity of breathing problems-and sleep, specifically sleep-wake behavior problems and daytime sleepiness during activities. Caregivers provided demographic information by telephone. RESULTS: Night awakenings and perceived severity of breathing problems were each independently associated with sleep-wake behavior problems and daytime sleepiness during activities. Youth report of perceived stress moderated the association between perceived severity of breathing problems and sleep-wake behavior problems, and perceived severity of breathing problems and daytime sleepiness during activities. CONCLUSIONS: Results suggest the importance of interventions that consider undiagnosed asthma and its effects on sleep indicators related to daytime functioning in this high risk group of youth. This study highlights the need for interventions that consider asthma severity, nocturnal asthma, and sleep problems among urban adolescents with no asthma diagnosis. PMID- 26149308 TI - Correlates to Human Papillomavirus Vaccination Status and Willingness to Vaccinate in Low-Income Philadelphia High School Students. AB - BACKGROUND: Little is known about the correlates of human papillomavirus (HPV) vaccination or willingness to be vaccinated in urban, minority adolescents. METHODS: Using responses to the 2013 Youth Risk Behavior Survey in Philadelphia, a random sample of high schools provided weighted data representing 20,941 9th to 12th graders. Stratified by either having had or willingness to have the vaccine, bivariate analysis with sexual behavior, preventive health behaviors, mental health, substance use, and demographic characteristics were examined and then multivariable regression models were developed to estimate significant correlates. RESULTS: Respondents were 52.3% female, 84.4% non-White, and 65.9% >=16 years; 43% reported having had the HPV vaccine, and of those not vaccinated, 66% reported willingness to be vaccinated. Logistic regression models indicate that females (odds ratio [OR] = 3.12, p < .01) and those reporting human immunodeficiency virus (HIV) testing (OR = 2.10, p < .01) were more likely to be vaccinated. Those reporting condom use during last intercourse (OR = 0.40; p = .05) and current marijuana use (OR = 0.37; p = .03) were less likely to indicate willingness to be vaccinated. CONCLUSIONS: Important areas for intervention include addressing misconceptions or feelings of "immunity," especially for those using condoms. Understanding the correlation between HIV testing and HPV vaccination is also an important intervention opportunity for schools hoping to increase adolescent vaccination rates. PMID- 26149309 TI - Implementing a School-Located Vaccination Program in Denver Public Schools. AB - BACKGROUND: School-located vaccination (SLV) offers an opportunity to deliver vaccines to students, particularly those without a primary care provider. METHODS: This SLV program offered 2 clinics at each of 20 elementary schools (influenza vaccine) and 3 clinics at each of 7 middle/preschool-eighth-grade schools (adolescent platform plus catch-up vaccines) during the 2009-2010 and 2010-2011 school years. Established programmatic processes for immunization delivery in an outreach setting were used. Billing and vaccine inventory management processes were developed. Vaccines from the federal Vaccines for Children program were used for eligible students. Third-party payers were billed for insured students; parents were not billed for services. RESULTS: The proportion of enrolled students who received at least 1 dose of vaccine increased from year 1 to year 2 (elementary: 28% to 31%; middle: 12% to 19%). Issues identified and addressed included program planning with partners, development and implementation of billing processes, development of a solution to adhere to the Family Educational Rights and Privacy Act requirements, development and utilization of an easy-to-comprehend consent form, and implementation of standard work procedures. CONCLUSIONS: This SLV program offered an alternative approach for providing vaccinations to students outside of the primary care setting. To be successful, ongoing partnerships are needed. PMID- 26149310 TI - Extracurricular Activities and Bullying Perpetration: Results From a Nationally Representative Sample. AB - BACKGROUND: Bullying is a widespread problem for school-aged children and adolescents. Interventions to reduce bullying are not well disseminated. Extracurricular involvement is, however, common. This study aims to examine the relationship between parent-reported participation in extracurricular activities and bullying perpetration. METHODS: Using the 2011 National Survey of Children's Health, 62,215 interviews with parents of children 6 to 17 were analyzed. Extracurricular categories of sports only, sports + nonsport, nonsport only, and no activities were based on parental response to questions regarding sport teams/lessons, clubs, and organizations. Bullying was derived from report of the child "bullying or being cruel/mean to others." Weighted bivariate analyses, logistic regression, and sex/race/ethnicity/age stratified analyses were conducted. RESULTS: Eighty percent of children participated in extracurricular activities: 8% sports, 48% sports + nonsports, and 24% nonsports. Bullying perpetration was reported in 15% of the sample. Compared with those not participating in extracurricular activities, the odds of bullying were significantly lower for children who participated in sports + nonsports (Adjusted odds ratio (AOR) 0.67, 95% confidence interval [CI] 0.57-0.79) and nonsport only (AOR 0.82, 95% CI 0.70-0.97). Stratified analyses showed attenuated effects of extracurricular activities for boys and for Hispanics. CONCLUSIONS: Children who participate in a variety of extracurricular activities exhibit the least frequent bullying perpetration. PMID- 26149311 TI - Homelessness and Sexual Identity Among Middle School Students. AB - BACKGROUND: Lesbian, gay, bisexual, or questioning (LGBQ) high school students experience higher rates of homelessness than their heterosexual peers. Moreover, LGBQ high school students are more likely to stay in riskier locations (eg, with a stranger) and less likely to stay in a shelter. This study tested whether these trends also apply to middle school students. METHODS: Using representative data, we examined sexual identity and homelessness among Los Angeles Unified School District middle school students. RESULTS: Nearly 10% of middle school students identified as LGBQ and 23.5% experienced at least 1 night of homelessness during the previous year. Contrary to high school data, LGBQ students did not experience higher rates of homelessness overall. However, when limiting the sample to students who had experienced homelessness, LGBQ students were more than 5 times as likely as heterosexual students to have stayed in a public place and 63% as likely to have stayed in a shelter. CONCLUSIONS: Lesbian, gay, bisexual, or questioning students are more likely to experience public homelessness. Schools must implement homelessness surveillance systems to assist in identifying early episodes of homelessness, thereby reducing the likelihood of poor physical and mental health outcomes associated with chronic homelessness. PMID- 26149312 TI - Adoption of Safe Routes to School in Canadian and the United States Contexts: Best Practices and Recommendations. AB - BACKGROUND: Declines in physical activity (PA) in children and youth have contributed to increases in childhood overweight and obesity. The Safe Routes to School (SRTS) program was developed to promote school active transportation (AT) and reverse the trend. METHODS: Adopting concepts of a realist approach, this article seeks to understand strategies of adoption that worked in the Canadian and United States context. Inclusion criteria consisted of adoption of SRTS program, identification and definition of SRTS, implementation in Canada /United States, and partnership identified. RESULTS: Partnerships focused on increasing the number of children using AT to school. With unique political and funding atmospheres, a common strategy was developing multilevel comprehensive partnerships to mobilize knowledge and resources, as well as to align intervention planning. Key successes, tools used to measure success, as well as benefits, challenges and lessons learned from partnerships were identified. CONCLUSION: This article is the first attempt to examine SRTS at the state/provincial/city level to understand key adoption strategies using a realist approach. It found collaborative community-research partnerships that initiated SRTS and created cultural shifts in communities from the individual to policy level. Researchers, schools and communities interested in increasing school AT should consider SRTS as a valuable approach. PMID- 26149313 TI - School-Based Sex Education and Neuroscience: What We Know About Sex, Romance, Marriage, and Adolescent Brain Development. AB - BACKGROUND: Many school-based abstinence-only sex education curricula state that sexual activity outside of marriage is likely to have harmful psychological effects. Recent advances in neuroscience have expanded our understanding of the neural underpinnings of romantic love, marriage, sexual desire, and sexual behavior and improved our understanding of adolescent brain development. METHODS: In this article, we review recent advances in neuroscience and clarify what is known about the link between neural development and adolescent romantic and sexual behavior and what opportunities exist for future research. RESULTS: Whereas the evidence from neuroscience does not yet allow for clear conclusions about the cost or benefits of early romantic relationships and sexual behavior, it does indicate that providing developmentally appropriate education contributes to lifelong sexual health. CONCLUSIONS: Developing policies and practices for school-based sex education that reflect current research will best support the sexual and reproductive health of adolescents throughout their lives. PMID- 26149315 TI - ? PMID- 26149314 TI - Multi-Wavelength Photoacoustic Visualization of High Intensity Focused Ultrasound Lesions. AB - High intensity focused ultrasound (HIFU) thermal therapies are limited by deficiencies in existing image-guidance techniques. Previous studies using single wavelength photoacoustic (PA) imaging have demonstrated that HIFU lesions generate contrast with respect to native tissues but have not sufficiently assessed lesion extent. The purpose of this study is to demonstrate feasibility of characterization of in vitro HIFU ablation lesion dimensions using 3D multi wavelength PA imaging. Fresh porcine cardiac and liver tissue samples were embedded in agar phantoms and ablated using a 2.5 MHz small-animal HIFU system. Both 2D and 3D multi-wavelength photoacoustic-ultrasonic (PAUS) scans were performed in the near-infrared (NIR) range to characterize the change in the absorption spectrum of tissues following ablation and were compared to stained gross pathology to assess treatment margins and lesion extent. Comprehensive 2D multi-wavelength PA imaging yielded a spectrum in ablated tissue that did not display the characteristic local maximum in the optical absorption spectrum of deoxy-hemoglobin (Hb) near 760 nm. Two-dimensional tissue characterization map (TCM) images reconstructed from 3D TCM volumes reliably characterized lesion area and showed >70% area agreement with stained gross pathology. In addition, tissue samples were heated via water bath and concurrently interrogated with 2D PAUS imaging. PA signal exhibited an initial amplitude increase across all wavelengths, corresponding to an initial temperature increase, before then exhibiting a spectral change. This study suggests that multi-wavelength PA imaging has potential to obtain accurate characterization of HIFU lesion extent and may be better suited to guide HIFU ablation therapies during clinical treatments than single-wavelength methods. PMID- 26149318 TI - Letter to the Editor, "Osterix Regulates Tooth Root Formation in a Site-specific Manner". PMID- 26149319 TI - Response to Letter to the Editor, "Osterix Regulates Tooth Root Formation in a Site-specific Manner". PMID- 26149320 TI - Axonal Degeneration in Dental Pulp Precedes Human Primary Teeth Exfoliation. AB - The dental pulp in human primary teeth is densely innervated by a plethora of nerve endings at the coronal pulp-dentin interface. This study analyzed how the physiological root resorption (PRR) process affects dental pulp innervation before exfoliation of primary teeth. Forty-four primary canine teeth, classified into 3 defined PRR stages (early, middle, and advanced) were fixed and demineralized. Longitudinal cryosections of each tooth were stained for immunohistochemical and quantitative analysis of dental pulp nerve fibers and associated components with confocal and electron microscopy. During PRR, axonal degeneration was prominent and progressive in a Wallerian-like scheme, comprising nerve fiber bundles and nerve endings within the coronal and root pulp. Neurofilament fragmentation increased significantly during PRR progression and was accompanied by myelin degradation and a progressive loss of myelinated axons. Myelin sheath degradation involved activation of autophagic activity by Schwann cells to remove myelin debris. These cells expressed a sequence of responses comprising dedifferentiation, proliferative activity, GAP-43 overexpression, and Bungner band formation. During the advanced PRR stage, increased immune cell recruitment within the dental pulp and major histocompatibility complex (MHC) class II upregulation by Schwann cells characterized an inflammatory condition associated with the denervation process in preexfoliative primary teeth. The ensuing loss of dental pulp axons is likely to be responsible for the progressive reduction of sensory function of the dental pulp during preexfoliative stages. PMID- 26149321 TI - Optimizing Value From Cardiac Rehabilitation: A Cost-Utility Analysis Comparing Age, Sex, and Clinical Subgroups. AB - OBJECTIVE: To assess the cost utility of a center-based outpatient cardiac rehabilitation program compared with no program within patient subgroups on the basis of age, sex, and clinical presentation (acute coronary syndrome [ACS] or non-ACS). METHODS: We performed a cost-utility analysis from a health system payer perspective to compare cardiac rehabilitation with no cardiac rehabilitation for patients who had a cardiac catheterization. The Markov model was stratified by clinical presentation, age, and sex. Clinical, quality-of-life, and cost data were provided by the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology. RESULTS: The incremental cost per quality-adjusted life-year (QALY) gained for cardiac rehabilitation varies by subgroup, from $18,101 per QALY gained to $104,518 per QALY gained. There is uncertainty in the estimates due to uncertainty in the clinical effectiveness of cardiac rehabilitation. Overall, the probabilistic sensitivity analysis found that 75% of the time participation in cardiac rehabilitation is more expensive but more effective than not participating in cardiac rehabilitation. CONCLUSION: The cost-effectiveness of cardiac rehabilitation varies depending on patient characteristics. The current analysis indicates that cardiac rehabilitation is most cost effective for those with an ACS and those who are at higher risk for subsequent cardiac events. The findings of the current study provide insight into who may benefit most from cardiac rehabilitation, with important implications for patient referral patterns. PMID- 26149322 TI - Strategic purchasing reform in Estonia: Reducing inequalities in access while improving care concentration and quality. AB - As of 2014, the Estonian Health Insurance Fund has adopted new purchasing procedures and criteria, which it now has started to implement in specialist care. Main changes include (1) redefined access criteria based on population need rather than historical supply, which aim to achieve more equal access of providers and specialties; (2) stricter definition and use of optimal workload criteria to increase the concentration of specialist care (3) better consideration of patient movement; and (4) an increased emphasis on quality to foster quality improvement. The new criteria were first used in the contract cycle that started in 2014 and resulted in fewer contracted providers for a similar volume of care compared to the previous contract cycle. This implies that provision of specialized care has become concentrated at fewer providers. It is too early to draw firm conclusions on the impact on care quality or on actors, but the process has sparked debate on the role of selective contracting and the role of public and private providers in Estonian health care. Lastly, the Estonian experience may hold important lessons for other countries looking to overcome inequalities in access while concentrating care and improving care quality. PMID- 26149323 TI - Prevalence and Frequency of mHealth and eHealth Use Among US and UK Smokers and Differences by Motivation to Quit. AB - BACKGROUND: Both mHealth and eHealth interventions for smoking cessation are rapidly being developed and tested. There are no data on use of mHealth and eHealth technologies by smokers in general or by smokers who are not motivated to quit smoking. OBJECTIVE: The aims of our study were to (1) assess technology use (eg, texting, social media, Internet) among smokers in the United States and United Kingdom, (2) examine whether technology use differs between smokers who are motivated to quit and smokers who are not motivated to quit, (3) examine previous use of technology to assist with smoking cessation, and (4) examine future intentions to use technology to assist with smoking cessation. METHODS: Participants were 1000 adult smokers (54.90%, 549/1000 female; mean age 43.9, SD 15.5 years; US: n=500, UK: n=500) who were recruited via online representative sampling strategies. Data were collected online and included demographics, smoking history, and frequency and patterns of technology use. RESULTS: Among smokers in general, there was a high prevalence of mobile and smartphone ownership, sending and receiving texts, downloading and using apps, using Facebook, and visiting health-related websites. Smokers who were unmotivated to quit were significantly less likely to own a smartphone or handheld device that connects to the Internet than smokers motivated to quit. There was a significantly lower prevalence of sending text messages among US smokers unmotivated to quit (78.2%, 179/229) versus smokers motivated to quit (95.0%, 229/241), but no significant differences between the UK groups (motivated: 96.4%, 239/248; unmotivated: 94.9%, 223/235). Smokers unmotivated to quit in both countries were significantly less likely to use a handheld device to read email, play games, browse the Web, or visit health-related websites versus smokers motivated to quit. US smokers had a high prevalence of app downloads regardless of motivation to quit, but UK smokers who were motivated to quit had greater prevalence of app downloads than smokers unmotivated to quit. US smokers were significantly more likely to have a Facebook account (87.0%, 435/500) than UK smokers (76.4%, 382/500), but smokers unmotivated to quit in both countries used Facebook less frequently than smokers motivated to quit. Smokers who were unmotivated to quit were less likely to have used eHealth or mHealth platforms to help them quit smoking in the past and less likely to say that they would use them for smoking cessation in the future. CONCLUSIONS: Although smokers unmotivated to quit make less use of technology than smokers motivated to quit, there is sufficient prevalence to make it worthwhile to develop eHealth and mHealth interventions to encourage cessation. Short and low-effort communications, such as text messaging, might be better for smokers who are less motivated to quit. Multiple channels may be required to reach unmotivated smokers. PMID- 26149324 TI - Mitochondrial population genomic analyses reveal population structure and demography of Indian Plasmodium falciparum. AB - Inference on the genetic diversity of Plasmodium falciparum populations could help in better management of malaria. A very recent study with mitochondrial (mt) genomes in global P. falciparum had revealed interesting evolutionary genetic patterns of Indian isolates in comparison to global ones. However, no population genetic study using the whole mt genome sequences of P. falciparum isolates collected in the entire distribution range in India has yet been performed. We herewith have analyzed 85 whole mt genomes (48 already published and 37 entirely new) sampled from eight differentially endemic Indian locations to estimate genetic diversity and infer population structure and historical demography of Indian P. falciparum. We found 19 novel Indian-specific Single Nucleotide Polymorphisms (SNPs) and 22 novel haplotypes segregating in Indian P. falciparum. Accordingly, high haplotype and nucleotide diversities were detected in Indian P. falciparum in comparison to many other global isolates. Indian P. falciparum populations were found to be moderately sub-structured with four different genetic clusters. Interestingly, group of local populations aggregate to form each cluster; while samples from Jharkhand and Odisha formed a single cluster, P. falciparum isolates from Asom formed an independent one. Similarly, Surat, Bilaspur and Betul formed a single cluster and Goa and Mangalore formed another. Interestingly, P. falciparum isolates from the two later populations were significantly genetically differentiated from isolates collected in other six Indian locations. Signature of historical population expansion was evident in five population samples, and the onset of expansion event was found to be very similar to African P. falciparum. In agreement with the previous finding, the estimated Time to Most Recent Common Ancestor (TMRCA) and the effective population size were high in Indian P. falciparum. All these genetic features of Indian P. falciparum with high mt genome diversity are somehow similar to Africa, but quite different from other Asian population samples. PMID- 26149326 TI - Clean Photothermal Heating and Controlled Release from Near-Infrared Dye Doped Nanoparticles without Oxygen Photosensitization. AB - The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser induced heating (no production of (1)O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive (1)O2, leading to bleaching of the dye and also decomposition of coencapsulated payload such as the drug doxorubicin. Croc dye was especially useful as a photothermal agent for laser-controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water-soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications. PMID- 26149327 TI - Influence of copper oxide nanoparticle shape on bioaccumulation, cellular internalization and effects in the estuarine sediment-dwelling polychaete, Nereis diversicolor. AB - CuO nanoparticles (NPs) released into the aquatic environment will likely accumulate in the sediment. Here we synthesized and characterized CuO NPs with different shapes and thus sizes: spheres, rods and spindles. Nereis diversicolor were exposed for 10 days to control sediment or sediment spiked with CuO NPs or aqueous Cu (Cu-Aq, CuCl2) at 7, 70 and 140 MUg Cu g(-1) dw sediment. Cu from all Cu treatments accumulated in worms in a concentration-dependent manner. Only Cu Aq decreased burrowing, suggesting that worms avoid Cu when added to sediment as Cu-Aq, but not CuO NPs. Transmission Electron Microscopy of gut sections indicated limited presence of CuO NP-like objects in the gut lumen, but evidence on whether accumulated Cu from CuO NP exposure was internalized as particles was not conclusive. Overall, bioavailability and avoidance was not influenced by particle shape or size, whereas Cu form (Cu-Aq vs particulate) and exposure concentration had significant impact. PMID- 26149328 TI - The power of next-generation sequencing as illustrated by the neuropeptidome of the crayfish Procambarus clarkii. AB - Transcriptomes of the crayfish Procambarus clarkii were analyzed for the presence of transcripts encoding neurohormones, neuropeptides and their receptors. A total of 58 different transcripts were found to encode such ligands and another 82 for their receptors. A very large number of the neuropeptide transcripts appeared to be complete and for those that were not only small parts seemed to be lacking. Transcripts for the neuropeptide GPCRs as well as for the putative receptors for insulin, neuroparsin and eclosion hormone were often also complete or almost so. Of particular interest is the presence of three different neuroparsin genes and two putative neuroparsin receptors. There are also three pigment dispersing hormones as well three likely receptors for these neuropeptides. CNMamide, calcitonin, CCRFamide, natalisin, trissin and relaxin appear to be new crustacean neuropeptides. The recently identified crustacean female sex hormone was also found and in the crayfish appears to be not only expressed in the eyestalk, but in the ovary as well (though not in the testis). Interestingly, there are two other proteins in the crayfish with a structure similar to crustacean female sex hormone, that could be precursors of neurohormones, but these are not expressed by the ovary. The ovary also appears to contain significant numbers of transcripts encoding pigment dispersing hormones, CNMamide as well as glycoprotein B5, but not glycoprotein A2. PMID- 26149329 TI - Inappropriate shock in a subcutaneous ICD due to interference with a street lantern. PMID- 26149330 TI - Supracristal ventricular septal defect in adults: Is it time for a paradigm shift? AB - BACKGROUND: To determine the risk and predictors of progression of aortic regurgitation (AR) and other adverse events (AE) in adults with supracristal ventricular septal defect (VSD). METHODS: Retrospective observational study of 62 adults with supracristal VSD followed at the Mayo Clinic from 1994 to 2013. Freedom from AR progression was compared by age and racial groups (Asian vs non Asian). Predictors of AR progression were determined using Cox proportional hazard model. Composite AE endpoint was defined as AR progression, endocarditis, aneurysm of sinus of Valsalva (aSOV), and rupture of aSOV. Risk of AE was compared between group 1 (no surgical intervention) and group 2 (surgical intervention). RESULTS: Sixty-two patients aged 47(SD 12) years were followed for 13 (SD 5) years. Group 1=42/62 and group=20/62. Endpoint of AR progression and aSOV occurred in 13% and 20% respectively. Freedom from AR progression for the entire cohort was 88%, 86% and 86% at 5, 10 and 15 years respectively. Risk of AR progression was significantly lower in patients (aged <=40 years, p=0.008) but similar between Asians and non-Asians (p=0.57). Age <=40 years was an independent predictor of AR progression (hazard ratio [HR] 3.5, 95% CI 2.3-5.4, p=0.001). Composite AE endpoint occurred in 33% and 40% of group1 and 2 cohorts respectively, p=0.69. CONCLUSION: Adults with supracristal VSD are at lower risk for AR progression but higher risk for aSOV formation compared to historical pediatric cohorts. Younger age was a predictor of AR progression. Surgical intervention had no protective effect on complication rate. PMID- 26149331 TI - Real-time three-dimensional echocardiography: never before clinical efficacy looked so picturesque. AB - Over the years echocardiography has served the clinical cardiologist in a variety of clinical scenarios, assisting in patient diagnostic and therapeutic managements. With the advent of novel imaging modalities we now experience the renascence of imaging. As a result, the field of cardiovascular medicine is strongly connected to imaging, which in turn requires thorough knowledge of each modality's distinct advantages and limitations. In this concise review we present up-to-date knowledge with regard to real-time three-dimensional echocardiography and its implementation in clinical practice. PMID- 26149332 TI - Left atrial thrombosis due to heparin-induced thrombocytopenia. PMID- 26149333 TI - Campylobacter jejuni-related cardiomyopathy: Unknown entity or yet underreported? PMID- 26149334 TI - Addition of copeptin improves diagnostic performance of point-of-care testing (POCT) for cardiac troponin T in early rule-out of myocardial infarction - A pilot study. AB - BACKGROUND: Point of care testing (POCT) assays for cardiac troponin (cTn) are hampered by lower analytical sensitivity and thus suboptimal rule-out of myocardial infarction (MI). We investigated, whether additional measurement of copeptin using an ultrasensitive assay improves diagnostic performance of POCT for cTn T compared to a high sensitivity troponin T (hsTnT) assay. METHODS: 131 patients with suspected acute coronary syndrome were prospectively enrolled in our center 08/2010 to 11/2011. In blood samples obtained at presentation, ultrasensitive copeptin (Kryptor, BRAHMS) and two commercially available POCT assays, AQT90 Flex Radiometer (Radiometer) and Cobas h232 POC-System (Cobas), were tested. HsTnT (Cobas E411, Roche) at baseline and after 3 and 6h in the central laboratory served as reference. RESULTS: Copeptin improved rule-out of non-STEMI combined with all tested troponin assays. Addition of copeptin increased sensitivity of Cobas from 67.9% (95% CI: 0.506; 0.852) to 89.3% (95% CI: 0.778; 1.007) and Radiometer from 71.4% (95% CI: 0.547; 0.882) to 85.7% (95% CI: 0.728; 0.987), achieving the sensitivity of hsTnT alone at admission of 85.7% (95% CI: 0.728; 0.987). The area under the curve (AUC) of Radiometer (0.822) was numerically but insignificantly (p=0.17) higher than AUC of Cobas (0.725). Addition of copeptin increased AUC of Radiometer to 0.826 (p=0.96) and AUC of Cobas to 0.814 (p=0.20). CONCLUSIONS: Additional use of ultrasensitive copeptin improves diagnostic performance of conventional sensitive POCT assays overcoming lower sensitivities at the cost of a drop of clinical specificity. When hsTn is temporarily unavailable, copeptin and POCT for cTn may allow initial evaluation at a comparable performance as hsTnT at admission. PMID- 26149335 TI - Gastroesophageal reflux disease and atrial fibrillation. PMID- 26149336 TI - Thyrotoxic pericarditis: An underappreciated phenomenon. PMID- 26149337 TI - An extremely rare complication due to percutaneous coronary intervention: Aortic perforation. PMID- 26149338 TI - Scaffolding of a bacterial genome using MinION nanopore sequencing. AB - Second generation sequencing has revolutionized genomic studies. However, most genomes contain repeated DNA elements that are longer than the read lengths achievable with typical sequencers, so the genomic order of several generated contigs cannot be easily resolved. A new generation of sequencers offering substantially longer reads is emerging, notably the Pacific Biosciences (PacBio) RS II system and the MinION system, released in early 2014 by Oxford Nanopore Technologies through an early access program. The latter has highly advantageous portability and sequences samples by measuring changes in ionic current when single-stranded DNA molecules are translocated through nanopores. We show that the MinION system produces long reads with high mapability that can be used for scaffolding bacterial genomes, despite currently producing substantially higher error rates than PacBio reads. With further development we anticipate that MinION will be useful not only for assembling genomes, but also for rapid detection of organisms, potentially in the field. PMID- 26149339 TI - Biocompatible films with tailored spectral response for prevention of DNA damage in skin cells. AB - A hybrid nanostructured organic-in-organic biocompatible film capable of efficiently blocking a preselected range of ultraviolet light is designed to match the genotoxic action spectrum of human epithelial cells. This stack protects cultured human skin cells from UV-induced DNA lesions. As the shielding mechanism relies exclusively on reflection, the secondary effects due to absorption harmful radiation are prevented. PMID- 26149340 TI - Does quitting smoking decrease the risk of midlife hot flashes? A longitudinal analysis. AB - Epidemiological studies have shown that cigarette smoking is associated with an increased risk of midlife hot flashes; however, the effect of quitting smoking on this risk is unclear. The purpose of this study was to examine the effect of quitting smoking on hot flashes using data from 761 women aged 45 to 54 years of age at baseline followed for 1 to 7 years. Results showed that women who quit smoking were less likely to suffer from hot flashes, less likely to have severe hot flashes, and less likely to have frequent hot flashes than women who continued to smoke (OR=0.55, 0.80, 0.76), but were more likely to suffer from any hot flashes, more severe hot flashes, and more frequent hot flashes than women who never smoked (OR=2.55, 1.68, 1.46). Subset analysis of the 353 women who had ever smoked found that women who had quit smoking for longer than 5 years had significantly lower odds, severity, and frequency of hot flashes than women who had continued smoking (OR=0.36, 0.62, 0.63) or women who had quit in the previous 5 years (OR=0.66, 0.77, 0.69). These findings suggest that that early smoking cessation programs may improve women's well-being during the menopausal transition. PMID- 26149341 TI - Preclinical development of small-molecular-weight folate-based radioconjugates: a pharmacological perspective. AB - The folate receptor (FR) has attracted attention as a target structure because of its frequent expression in cancer cells (FR-alpha) and activated macrophages (FR beta). The vitamin folic acid has served as a promising targeting ligand allowing selective delivery of attached radionuclides suitable for imaging of the diseased sites and for therapeutic application. A large number of folate radioconjugates with variable chemical structures have been developed over the last 25 years. Accumulation of radioactivity in healthy organs and tissues was always seen in the kidneys due to the expression of the FR in the proximal tubule cells. In some cases unspecific uptake of radiofolates was also seen in the liver and the intestinal tract. To address this situation and improve the target-to-off-target ratios of accumulated radioactivity several strategies were undertaken, including chemical modifications of the folate conjugates, selection of appropriate radionuclides and application of drug combinations. Depending on the radionuclide which was employed various chelators and linker entities were investigated and additional functionalities with albumin-binding properties were tested with the aim to increase the serum half-life of the radioconjugates. A number of diagnostic radionuclides ((99m)Tc, (111)In, (67)Ga, (155)Tb, (125)I) emitting gamma-radiation were employed for single photon emission computed tomography (SPECT) and, beta(+)-emitting radionuclides ((68)Ga, 44Sc, (152)Tb, (18)F) were used for positron emission tomography (PET). Moreover, therapeutic radionuclides emitting beta(-)-particles ((177)Lu, (161)Tb, (47)Sc, (131)I) and alpha-particles ((149)Tb) were also used with folate conjugates. The present review focuses on the development of radiofolates and their in vivo properties and on strategies which were employed to modify their pharmacokinetic and pharmacodynamic properties. PMID- 26149343 TI - The state of the future is solid. PMID- 26149342 TI - Function of a p24 Heterodimer in Morphogenesis and Protein Transport in Penicillium oxalicum. AB - The lignocellulose degradation capacity of filamentous fungi has been widely studied because of their cellulase hypersecretion. The p24 proteins in eukaryotes serve important functions in this secretory pathway. However, little is known about the functions of the p24 proteins in filamentous fungi. In this study, four p24 proteins were identified in Penicillium oxalicum. Six p24 double-deletion strains were constructed, and further studies were carried out with the DeltaerpDeltapdelta strain. The experimental results suggested that Erp and Pdelta form a p24 heterodimer in vivo. This p24 heterodimer participates in important morphogenetic events, including sporulation, hyphal growth, and lateral branching. The results suggested that the p24 heterodimer mediates protein transport, particularly that of cellobiohydrolase. Analysis of the intracellular proteome revealed that the DeltaerpDeltapdelta double mutant is under secretion stress due to attempts to remove proteins that are jammed in the endomembrane system. These results suggest that the p24 heterodimer participates in morphogenesis and protein transport. Compared with P. oxalicum Deltaerp, a greater number of cellular physiological pathways were impaired in DeltaerpDeltapdelta. This finding may provide new insights into the secretory pathways of filamentous fungi. PMID- 26149344 TI - A Shear Strain Route Dependency of Martensite Formation in 316L Stainless Steel. AB - In this study, the effect of simple shearing on microstructure evolution and mechanical properties of 316L austenitic stainless steel were investigated. Two different shear strain routes were obtained by twisting cylindrical specimens in the forward and backward directions. The strain-induced martensite phase was effectively obtained by alteration of the routes. Formation of the martensite phase clearly resulted in significant hardening of the steel. Grain-size reduction and strain-induced martensitic transformation within the deformed structures of the strained specimens were characterized by scanning electron microscopy - electron back-scattered diffraction, X-ray diffraction, and the TEM ASTAR (transmission electron microscopy - analytical scanning transmission atomic resolution, automatic crystal orientation/phase mapping for TEM) system. Significant numbers of twin networks were formed by alteration of the shear strain routes, and the martensite phases were nucleated at the twin interfaces. PMID- 26149345 TI - Microscopy and Microanalysis of an Extreme Case of Salt and Biodegradation in 17th Century Wall Paintings. AB - The present study characterizes the main deterioration mechanisms affecting the early 17th frescoes of Casa de Fresco, the only known example in Portugal of a semi-underground leisure room richly decorated with a balcony over a water well. Frescoes from the vault are at risk due to salt weathering and biodeterioration. The aim of the research was identification of the deterioration materials, determination of their origin, and their effect on the frescoes before future intervention. Scanning electron microscopy with an energy-dispersive X-ray detector (SEM-EDS) was used to determine salt morphology and microanalysis. The mineralogical characterization was performed by X-ray powder diffraction, complemented with u-Raman and u-Fourier transform infrared spectroscopy. Biological assessment was evaluated with optical microscopy and SEM-EDS. Bacterial and fungal isolation and identification were performed using standard culture media and methods according to Bergey's Manual of Systematic Bacteriology and from the Compendium of Soil Fungi. The results show that Ca and Ca-Mg carbonates from the paint renderings are the predominant salt species affecting the site. Bacterial strains from the genera Bacillus and Pseudomonas and fungal strains from the Cladosporium spp. and Penicillium spp. were isolated in the salt formations, within and between the mortar layers. Azurite, malachite, and smalt paint layers are the most affected by the weathering conditions. PMID- 26149346 TI - When will Low-Contrast Features be Visible in a STEM X-Ray Spectrum Image? AB - When will a small or low-contrast feature, such as an embedded second-phase particle, be visible in a scanning transmission electron microscopy (STEM) X-ray map? This work illustrates a computationally inexpensive method to simulate X-ray maps and spectrum images (SIs), based upon the equations of X-ray generation and detection. To particularize the general procedure, an example of nanostructured ferritic alloy (NFA) containing nm-sized Y2Ti2O7 embedded precipitates in ferritic stainless steel matrix is chosen. The proposed model produces physically appearing simulated SI data sets, which can either be reduced to X-ray dot maps or analyzed via multivariate statistical analysis. Comparison to NFA X-ray maps acquired using three different STEM instruments match the generated simulations quite well, despite the large number of simplifying assumptions used. A figure of merit of electron dose multiplied by X-ray collection solid angle is proposed to compare feature detectability from one data set (simulated or experimental) to another. The proposed method can scope experiments that are feasible under specific analysis conditions on a given microscope. Future applications, such as spallation proton-neutron irradiations, core-shell nanoparticles, or dopants in polycrystalline photovoltaic solar cells, are proposed. PMID- 26149347 TI - Three-dimensional reference interaction site model self-consistent field analysis of solvent and substituent effects on the absorption spectra of Brooker's merocyanine. AB - Solvent and substituent effects on the absorption spectra of Brooker's merocyanine (BM) are investigated using the three-dimensional reference interaction site model self-consistent field method and time-dependent density functional theory. The pi-pi* excitation energies are computed for BM and its derivative 2,6-di-tert-butyl (di-t-Bu) BM. The behaviors of the computed excitation energies with increasing solvent polarity are in good agreement with those of the corresponding experimental measurements. In addition, analysis of the solute-solvent interaction energies and spatial distribution functions reveals that the effects of the solvent on the absorption spectra are reduced by the steric hindrance of the t-Bu groups. Furthermore, from the difference in the solute-solvent interaction energies of BM and di-t-Bu BM, it is shown that the effect of the t-Bu substituents on the absorption spectrum is greater in high polarity solvents. PMID- 26149348 TI - Assessment of neurovascular dynamics during transient ischemic attack by the novel integration of micro-electrocorticography electrode array with functional photoacoustic microscopy. AB - This study developed a novel system combining a 16-channel micro electrocorticography (MUECoG) electrode array and functional photoacoustic microscopy (fPAM) to examine changes in neurovascular functions following transient ischemic attack (TIA) in rats. To mimic the pathophysiology of TIA, a modified photothrombotic ischemic model was developed by using 3 min illumination of 5 mW continuous-wave (CW) green laser light focusing on a distal branch of the middle cerebral artery (MCA). Cerebral blood volume (CBV), hemoglobin oxygen saturation (SO2), somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were measured pre- and post-ischemia over a focal cortical region (i.e., 1.5*1.5 mm(2)). Unexpectedly, the SO2, peak-to-peak amplitude (PPA) of SSEPs and ADR recovered and achieved levels greater than the baseline values at the 4th hour post-ischemia induction without any intervention, whereas the CBV value only partially recovered. In other words, transient ischemia led to increased neural activity when the relative CBV was reduced, which may further compromise neural integrity or lead to subsequent vascular disease. This novel MUECoG-fPAM system complements currently available imaging techniques and represents a promising technology for studying neurovascular coupling in animal models. PMID- 26149350 TI - Preconception paternal stress in rats alters dendritic morphology and connectivity in the brain of developing male and female offspring. AB - The goal of this research was to examine the effect of preconception paternal stress (PPS) on the subsequent neurodevelopment and behavior of male and female offspring. Prenatal (gestational) stress has been shown to alter brain morphology in the developing brain, and is presumed to be a factor in the development of some adult psychopathologies. Our hypothesis was that paternal stress in the preconception period could impact brain development in the offspring, leading to behavioral abnormalities later in life. The purpose of this study was to examine the effect of preconception paternal stress on developing male and female offspring brain morphology in five brain areas; medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), parietal cortex (Par1), hippocampus (CA1) and nucleus accumbens (NAc). Alterations in dendritic measures and spine density were observed in each brain area examined in paternal stress offspring. Our two main findings reveal; (1) PPS alters brain morphology and organization and these effects are different than the effects of stress observed at other ages; and, (2) the observed dendritic changes were sexually dimorphic. This study provides direct evidence that PPS modifies brain architecture in developing offspring, including dendritic length, cell complexity, and spine density. Alterations observed may contribute to the later development of psychopathologies and maladaptive behaviors in the offspring. PMID- 26149349 TI - Micelle-Encapsulated Quantum Dot-Porphyrin Assemblies as in Vivo Two-Photon Oxygen Sensors. AB - Micelles have been employed to encapsulate the supramolecular assembly of quantum dots with palladium(II) porphyrins for the quantification of O2 levels in aqueous media and in vivo. Forster resonance energy transfer from the quantum dot (QD) to the palladium porphyrin provides a means for signal transduction under both one- and two-photon excitation. The palladium porphyrins are sensitive to O2 concentrations in the range of 0-160 Torr. The micelle-encapsulated QD-porphyrin assemblies have been employed for in vivo multiphoton imaging and lifetime-based oxygen measurements in mice with chronic dorsal skinfold chambers or cranial windows. Our results establish the utility of the QD-micelle approach for in vivo biological sensing applications. PMID- 26149351 TI - Activation of the insulin-signaling pathway in sciatic nerve and hippocampus of type 1 diabetic rats. AB - Peripheral neuropathy is a major complication associated with diabetes and central neuropathy characterized by Alzheimer's disease-like features in the brain is associated with increased dementia risk for patients with diabetes. Although glucose uptake into the cells of the nervous system is insulin independent, contribution of impaired insulin support is clearly recognized to play a role, however not yet fully understood, in the development of neuropathy. In this study, we assessed the direct role of insulin on the peripheral nervous system (PNS) and central nervous system (CNS) of insulin-dependent type 1 diabetic rats. Fresh sciatic nerve and hippocampus from control and diabetic rats were incubated with varied ex vivo concentrations of insulin and phosphorylation levels of insulin receptor and glycogen synthase kinase-3 (GSK3beta) were assessed by Western blot analysis. Both the sciatic nerve and hippocampus from type 1 diabetic rats were highly responsive to exogenous insulin with a significantly increased phosphorylation of insulin receptor and GSK3 compared to tissues from control rats. Further, sustained in vivo insulin delivery, not sufficient to restore normal blood glucose, normalized the activation of both insulin receptor and GSK3 in both PNS and CNS tissues. These results suggest that the insulin-signaling pathway is responsive to exogenous insulin in the nervous system of insulin-deficient type 1 diabetic rats and that constant insulin delivery restore normal nerve function and may protect PNS and CNS from damage. PMID- 26149353 TI - Biotic resistance limits the invasiveness of the western flower thrips, Frankliniella occidentalis (Thysanoptera: Thripidae), in Florida. AB - The spread of the western flower thrips, Frankliniella occidentalis (Pergande), has resulted in the world-wide destabilization of established integrated pest management programs for many crops. It is hypothesized that frequent exposure to insecticides in intensive agriculture selected for resistant populations, which allowed invasive populations in the eastern USA to overcome biotic resistance from the native community of species. Research conducted in Florida to understand the role of biotic factors in limiting the abundance of the western flower thrips is reviewed. Orius spp. (Hemiptera: Anthocoridae) are effective predators that suppress populations of thrips on crop and non-crop hosts in southern and northern Florida. Orius are more effective predators of the western flower thrips than the native flower thrips, F. tritici (Fitch) and F. bispinosa (Morgan). The native species are competitors of the western flower thrips. Excessive fertilization and the use of broad-spectrum insecticides in crop fields further enhances populations of the western flower thrips. Interactions with native species clearly limit the abundance of western flower thrips in Florida, but populations are abundant in fertilized crop fields where application of insecticides excludes predators and competitor species. PMID- 26149352 TI - The subclassification of papillary renal cell carcinoma does not affect oncological outcomes after nephron sparing surgery. AB - OBJECTIVES: To evaluate the oncological outcomes of papillary renal cell carcinoma (pRCC) following nephron sparing surgery (NSS) and to determine whether the subclassification type of pRCC could be a prognostic factor for recurrence, progression, and specific death. MATERIALS AND METHODS: An international multicentre retrospective study involving 19 institutions and the French network for research on kidney cancer was conducted after IRB approval. We analyzed data of all patients with pRCC who were treated by NSS between 2004 and 2014. RESULTS: We included 486 patients. Tumors were type 1 pRCC in 369 (76 %) cases and type 2 pRCC in 117 (24 %) cases. After a mean follow-up of 35 (1-120) months, 8 (1.6 %) patients experienced a local recurrence, 12 (1.5 %) had a metastatic progression, 24 (4.9 %) died, and 7 (1.4 %) died from cancer. Patients with type I pRCC had more grade II (66.3 vs. 46.1 %; p < 0.001) and less grade III (20 vs. 41 %; p < 0.001) tumors. Three-year estimated cancer-free survival (CFS) rate for type 1 pRCC was 96.5 % and for type 2 pRCC was 95.1 % (p = 0.894), respectively. Three year estimated cancer-specific survival rate for type 1 pRCC was 98.4 % and for type 2 pRCC was 97.3 % (p = 0.947), respectively. Tumor stage superior to pT1 was the only prognostic factor for CFS (HR 3.5; p = 0.03). CONCLUSION: Histological subtyping of pRCC has no impact on oncologic outcomes after nephron sparing surgery. In this selected population of pRCC tumors, we found that tumor stage is the only prognostic factor for cancer-free survival. PMID- 26149354 TI - Long-term follow-up of patients with an isolated ovarian recurrence after conservative treatment of epithelial ovarian cancer: review of the results of an international multicenter study comprising 545 patients. AB - OBJECTIVE: To determine the long-term outcomes of patients with an isolated ovarian recurrence after fertility sparing surgery (FSS) for epithelial ovarian cancer (EOC) and to evaluate the recurrence rates (and location) according to the new 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. DESIGN: Retrospective multicenter study. SETTING: Teams having reported recurrence after FSS for EOC. PATIENT(S): Four series comprising 545 patients undergoing FSS and 63 (12%) recurrences. INTERVENTION(S): FSS (salpingo oophorectomy for a majority of cases) for EOC. MAIN OUTCOMES MEASURE(S): Recurrences rates and characteristics of recurrent disease. RESULT(S): Among 63 recurrent patients, 24 (38%) recurrences were isolated on the spared ovary, and 39 (62%) arose at an extraovarian site. Among the patients with an isolated ovarian recurrence, three patients died after a median follow-up period of 186 months (range: 28-294 months). Among the patients with recurrent extraovarian disease, 24 died and 7 were alive with persistent disease after a median follow up period of 34 months (range: 3-231 months). The overall rate of isolated ovarian and extrapelvic recurrences was higher for grade 3 tumors (compared with grades 1/2). CONCLUSION(S): The long-term survival of patients with an isolated ovarian recurrence after FSS for EOC remains favorable. The prognosis of patients with an extraovarian recurrence is poor compared with those who have an isolated recurrent ovarian tumor. Grade 3 tumors (compared to grades 1/2) give rise to a higher rate of extraovarian recurrences. PMID- 26149355 TI - Risk factors for a suboptimal response to gonadotropin-releasing hormone agonist trigger during in vitro fertilization cycles. AB - OBJECTIVE: To identify risk factors for a suboptimal response to gonadotropin releasing hormone (GnRH) agonist trigger in in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): All 424 patients undergoing fresh IVF cycles (n = 500) between August 2007 and June 2013 in whom a GnRH agonist was used as all or part of the ovulation trigger. INTERVENTION(S): GnRH-antagonist-based IVF cycles triggered with leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin. MAIN OUTCOME MEASURE(S): Suboptimal response to GnRH-agonist trigger, as defined by a serum luteinizing hormone (LH) level <15 mIU/mL on the morning after trigger. RESULT(S): The rate of suboptimal response to the GnRH agonist trigger was 5.2%. Patients with a suboptimal hormone response had lower follicle-stimulating hormone (<0.1 vs. 3.48) and LH (<0.1 vs. 2.51) levels on day 2 of the cycle start, lower LH (0.109 vs. 0.596) on the day of trigger, and required longer stimulation and more gonadotropins than those with an adequate response. Suboptimal responders were also more likely to have irregular menses and be on long-term oral contraception. Patients with an undetectable LH on the day of trigger had a 25% chance of a suboptimal LH surge. In our study cohort, limiting the use of the GnRH-agonist trigger alone to patients with a trigger day LH >=0.5 would have reduced the rate of suboptimal response from 5.2% to 0.2%. CONCLUSION(S): Long-term hormonal contraception use is an independent risk factor for suboptimal response to GnRH-agonist trigger. Patients with very low endogenous serum LH levels on the day of LH trigger are at increased risk for a suboptimal GnRH-agonist trigger response. Understanding the at-risk phenotype and using trigger day LH as a marker for increased risk of suboptimal GnRH-agonist trigger response can be helpful for individualizing treatment and selecting a safe and efficacious trigger medication for patients undergoing IVF. PMID- 26149356 TI - A sweet view of reproduction. PMID- 26149357 TI - Metabotropic Glutamate Receptor Subtype 7 in the Bed Nucleus of the Stria Terminalis is Essential for Intermale Aggression. AB - Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of group III mGluRs, which localize to the presynaptic active zones of the mammalian central nervous system. Although histological, genetic, and electrophysiological studies ensure the importance of mGluR7, its roles in behavior and physiology remain largely unknown. Using a resident-intruder paradigm, we found a severe reduction in intermale aggressive behavior in mGluR7 knockout (KO) mice. We also found alterations in other social behaviors in male mGluR7 KO mice, including sexual behavior toward male intruders. Because olfaction is critical for rodent social behavior, including aggression, we performed an olfaction test, finding that mGluR7 KO mice failed to show interest in the smell of male urine. To clarify the olfactory deficit, we then exposed mice to urine and analyzed c-Fos immunoreactivity, discovering a remarkable reduction in neural activity in the bed nucleus of the stria terminalis (BNST) of mGluR7 KO mice. Finally, intra-BNST administration of the mGluR7-selective antagonist 6-(4-methoxyphenyl)-5-methyl-3 pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP) also reproduced the phenotype of mGluR7 KO mice, including reduced aggression and altered social interaction. Thus mGluR7 may work as an 'enhancer of neural activity' in the BNST and is important for intermale aggression. Our findings demonstrate that mGluR7 is essential for social behavior and innate behavior. Our study on mGluR7 in the BNST will shed light on future therapies for emotional disorders in humans. PMID- 26149362 TI - 25th Anniversary Article: Colloidal Quantum Dot Materials and Devices: A Quarter Century of Advances. PMID- 26149367 TI - Is sexual racism really racism? Distinguishing attitudes toward sexual racism and generic racism among gay and bisexual men. AB - Sexual racism is a specific form of racial prejudice enacted in the context of sex or romance. Online, people use sex and dating profiles to describe racialized attraction through language such as "Not attracted to Asians." Among gay and bisexual men, sexual racism is a highly contentious issue. Although some characterize discrimination among partners on the basis of race as a form of racism, others present it as a matter of preference. In May 2011, 2177 gay and bisexual men in Australia participated in an online survey that assessed how acceptably they viewed online sexual racism. Although the men sampled displayed diverse attitudes, many were remarkably tolerant of sexual racism. We conducted two multiple linear regression analyses to compare factors related to men's attitudes toward sexual racism online and their racist attitudes more broadly. Almost every identified factor associated with men's racist attitudes was also related to their attitudes toward sexual racism. The only differences were between men who identified as Asian or Indian. Sexual racism, therefore, is closely associated with generic racist attitudes, which challenges the idea of racial attraction as solely a matter of personal preference. PMID- 26149358 TI - A Critical Role for the GluA1 Accessory Protein, SAP97, in Cocaine Seeking. AB - A growing body of evidence indicates that the transport of GluA1 subunit containing calcium-permeable AMPA receptors (CP-AMPARs) to synapses in subregions of the nucleus accumbens promotes cocaine seeking. Consistent with these findings, the present results show that administration of the CP-AMPAR antagonist, Naspm, into the caudal lateral core or caudal medial shell of the nucleus accumbens attenuated cocaine priming-induced reinstatement of drug seeking. Moreover, viral-mediated overexpression of 'pore dead' GluA1 subunits (via herpes simplex virus (HSV) GluA1-Q582E) in the lateral core or medial shell attenuated the reinstatement of cocaine seeking. The overexpression of wild-type GluA1 subunits (via HSV GluA1-WT) in the medial shell, but not the lateral core, enhanced the reinstatement of cocaine seeking. These results indicate that activation of GluA1-containing AMPARs in subregions of the nucleus accumbens reinstates cocaine seeking. SAP97 and 4.1N are proteins involved in GluA1 trafficking to and stabilization in synapses; SAP97-GluA1 interactions also influence dendritic growth. We next examined potential roles of SAP97 and 4.1N in cocaine seeking. Viral-mediated expression of a microRNA that reduces SAP97 protein expression (HSV miSAP97) in the medial accumbens shell attenuated cocaine seeking. In contrast, a virus that overexpressed a dominant-negative form of a 4.1N C-terminal domain (HSV 4.1N-CTD), which prevents endogenous 4.1N binding to GluA1 subunits, had no effect on cocaine seeking. These results indicate that the GluA1 subunit accessory protein SAP97 may represent a novel target for pharmacotherapeutic intervention in the treatment of cocaine craving. PMID- 26149368 TI - Meta-analysis of anthropogenic habitat disturbance effects on animal-mediated seed dispersal. AB - Anthropogenic habitat disturbance is a strong biodiversity change driver that compromises not only the species persistence but also the ecological interactions in which they are involved. Even though seed dispersal is a key interaction involved in the recruitment of many tree species and in consequence critical for biodiversity maintenance, studies assessing the effect of different anthropogenic disturbance drivers on this interaction have not been performed under a meta analytical framework. We assessed the way habitat fragmentation and degradation processes affect species diversity (abundance and species richness) and interaction rates (i.e., fruit removal and visitation rates) of different groups of seed-disperser species at a global scale. We obtained 163 case studies from 37 articles. Results indicate that habitat degradation had a negative effect on seed disperser animal diversity, whereas habitat fragmentation had a negative effect on interaction rates. Birds and insects were more sensitive in terms of their diversity, whereas mammals showed a negative effect on interaction rates. Regarding habitat, both fragmentation and degradation had a negative effect on seed-disperser animal diversity only in temperate habitats, and negative effects on interaction rates in tropical and temperate habitats. Our results indicate that the impact of human disturbance on seed-disperser species and interactions is not homogeneous. On the contrary, the magnitude of effects seems to be dependent on the type of disturbance, taxonomic group under assessment, and geographical region where the human impact occurs. PMID- 26149369 TI - Eluxadoline: First Global Approval. AB - Eluxadoline (Viberzi(TM)), developed by Actavis (now Allergan), is an orally administered, first-in-class compound that functions as both a u-opioid receptor agonist and a delta-opioid receptor antagonist, and is indicated for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D) in adults. The agent was originally developed by Janssen Pharmaceutica. Eluxadoline has been approved in the US, and submissions to other global authorities are being contemplated or planned. This article summarizes the milestones in the development of eluxadoline leading to this first approval for IBS-D. PMID- 26149370 TI - Molecular cytogenetic analysis of monoecious hemp (Cannabis sativa L.) cultivars reveals its karyotype variations and sex chromosomes constitution. AB - Hemp (Cannabis sativa L., 2n = 20) is a dioecious plant. Sex expression is controlled by an X-to-autosome balance system consisting of the heteromorphic sex chromosomes XY for males and XX for females. Genetically monoecious hemp offers several agronomic advantages compared to the dioecious cultivars that are widely used in hemp cultivation. The male or female origin of monoecious maternal plants is unknown. Additionally, the sex chromosome composition of monoecious hemp forms remains unknown. In this study, we examine the sex chromosome makeup in monoecious hemp using a cytogenetic approach. Eight monoecious and two dioecious cultivars were used. The DNA of 210 monoecious plants was used for PCR analysis with the male-associated markers MADC2 and SCAR323. All monoecious plants showed female amplification patterns. Fluorescence in situ hybridization (FISH) with the subtelomeric CS-1 probe to chromosomes plates and karyotyping revealed a lack of Y chromosome and presence of XX sex chromosomes in monoecious cultivars with the chromosome number 2n = 20. There was a high level of intra- and intercultivar karyotype variation detected. The results of this study can be used for further analysis of the genetic basis of sex expression in plants. PMID- 26149371 TI - Effects of Cosolvents on the Folding and Catalytic Activities of the Hammerhead Ribozyme. AB - The RNA cleavage activity of the hammerhead ribozyme has been compared in various mixed aqueous solutions containing cosolvents. Kinetic analysis revealed that the tested cosolvents enhanced the ribozyme activity, particularly at low MgCl2 concentrations. These enhancements, in some cases of more than tenfold, resulted from a reduction in the Mg(2+) concentration required for substrate cleavage. An inverse correlation was found between the MgCl2 concentration essential for efficient catalysis and the dielectric constant values. In contrast, FRET measurements showed no substantial influence of cosolvents on the Mg(2+) -induced structural transitions. The results suggest that the solution environment has various effects on the Mg(2+) interactions involved in the catalysis and global folding of the ribozyme. PMID- 26149372 TI - A systematic review of the role of community pharmacies in improving the transition from secondary to primary care. AB - AIM: We set out to determine the potential contribution of community pharmacists to improve the transfer of care of patients from secondary to primary care settings. METHOD: We systematically reviewed the literature on interventions that involved community pharmacy post-discharge. We considered all relevant studies, including both randomized and non-randomized controlled trials, irrespective of patient population. Our primary outcome was any impact on patient and medication outcomes, while the secondary outcome was to identify intervention characteristics that influenced all reported outcomes. RESULTS: We retrieved 14 studies that met our inclusion criteria. There were four studies reporting outcomes relating to the identification and rectification of medication errors that were significantly improved with community pharmacy involvement. Other patient outcomes such as medication adherence and clinical control were not unanimously positively or negatively influenced via the inclusion of community pharmacy in a transfer of care post-discharge intervention. Some inconsistencies in implementation and process evaluation of interventions were found across the reviewed studies. This limited the accuracy with which true impact could be considered. CONCLUSIONS: There is evidence that interventions including a community pharmacist can improve drug related problems after discharge. However, impact on other outcomes is not consistent. Further studies are required which include process evaluations to describe fully the context of the intervention so as to determine better any influencing factors. Also applying more stringent controls and closer adherence to protocols in both intervention and control groups would allow clearer correlations to be made between the intervention and the outcomes. PMID- 26149373 TI - Double-site recognition of pathogenic bacterial whole cells based on an antibiotic-affinity strategy. AB - An antibiotic-affinity strategy was designed to detect pathogenic bacterial whole cells based on the strong affinity of the antibiotic agent to bind to the cell wall of the bacterium. Vancocin, a powerful glycopeptide antibiotic, was used as a molecular recognition agent for Staphylococcus aureus. To improve its specificity, IgG was utilized as the second recognition agent based on the binding between the Fc region of IgG and protein A in the cell wall. PMID- 26149374 TI - Modeling left and right atrial contributions to the ECG: A dipole-current source approach. AB - This paper presents the mathematical formulation, the numerical validation and several illustrations of a forward-modeling approach based on dipole-current sources to compute the contribution of a part of the heart to the electrocardiogram (ECG). Clinically relevant applications include identifying in the ECG the contributions from the right and the left atrium. In a Courtemanche based monodomain computer model of the atria and torso, 1000 dipoles distributed throughout the atrial mid-myocardium are found to be sufficient to reproduce body surface potential maps with a relative error <1% during both sinus rhythm and atrial fibrillation. When the boundary element method is applied to solve the forward problem, this approach enables fast offline computation of the ECG contribution of any anatomical part of the atria by applying the principle of superposition to the dipole sources. In the presence of a right-left activation delay (sinus rhythm), pulmonary vein isolation (sinus rhythm) or left-right differences in refractory period (atrial fibrillation), the decomposition of the ECG is shown to help interpret ECG morphology in relation to the atrial substrate. These tools provide a theoretical basis for a deeper understanding of the genesis of the P wave or fibrillatory waves in normal and pathological cases. PMID- 26149375 TI - Fracture Risk and Risk Factors for Osteoporosis. AB - BACKGROUND: As the population ages, diseases of the elderly are becoming more common, including osteoporosis. Ways to assess the risk of fracture and the distribution and effects of known risk factors for osteoporosis will be important in planning for future healthcare needs, as well as in the development of preventive strategies. METHODS: The study population included 6029 men and women aged 20-90 who underwent examination in the second follow-up wave of the Study of Health in Pomerania (SHIP-2) or in the basal SHIP-Trend Study. The risk of fracture was estimated on the basis of quantitative ultrasonography of the calcaneus. Prior fractures and risk factors for osteoporosis were ascertained in standardized interviews. RESULTS: 4.6% of the male subjects and 10.6% of the female subjects were judged to have an elevated risk of fracture. The corresponding percentages among subjects over age 65 were 8.8% for men and 28.2% for women. Even among subjects under age 55, risk factors for osteoporosis were associated with lower bone stiffness: the mean stiffness index was 103/98 (men/women) without risk factors, 99/96 with one risk factor, and 93/95 with more than one risk factor. Logistic regression analysis yielded an odds ratio of 1.89 (95% confidence interval: 1.44-2.50; p<0.01) for prevalent fractures among subjects aged 75 and older compared to subjects under age 55. CONCLUSION: The data indicate a high prevalence of osteoporosis from age 65 onward. These findings are consistent with those of other studies from Germany and across Europe. Younger men and women should already begin taking steps to counteract modifiable risk factors. PMID- 26149376 TI - Isocitrate Dehydrogenase Genes. PMID- 26149377 TI - Radioembolization as a Treatment Option. PMID- 26149378 TI - More Reliance on PET-CT Findings. PMID- 26149379 TI - Skeletal Scintigraphy Underrated. PMID- 26149380 TI - Mental Disorders in Early Childhood. AB - BACKGROUND: About 17% of all children suffer from a mental disorder in early childhood, defined as the period up to the age of 6 years. METHODS: This review is based on publications retrieved by a selective search in PubMed and the Web of Science, as well as on the authors' clinical and scientific experience. RESULTS: In children up to age 2, disorders of emotional and motor regulation are common (ca. 7%), as are feeding problems (25%), which persist in 2% of children to meet the diagnostic criteria for a feeding disorder. Reactive attachment disorder, a serious mental illness, has a prevalence of about 1%: it is more common among children in situations of increased risk, e.g., orphanages and foster homes. Preschool children can develop anxiety disorder and depressive disorder, as well as hyperactivity and behavioral disorders (the latter two mainly in boys). Parent training and parent-child psychotherapy have been found to be effective treatments. There is no evidence that psychotropic drugs are effective in early childhood. CONCLUSION: The diagnostician should act cautiously when assigning psychopathological significance to symptoms arising in early childhood but should still be able to recognize mental disorders early from the way they are embedded in the child's interactive relationships with parents or significant others, and then to initiate the appropriate treatment. Psychotherapy in this age group is still in need of validation by efficacy studies and longitudinal studies of adequate quality. PMID- 26149381 TI - stg fimbrial operon from S. Typhi STH2370 contributes to association and cell disruption of epithelial and macrophage-like cells. AB - BACKGROUND: Salmonella enterica serovar Typhi (S. Typhi) stg operon, encoding a chaperone/usher fimbria (CU), contributes to an increased adherence to human epithelial cells. However, one report suggests that the presence of the Stg fimbria impairs the monocyte--bacteria association, as deduced by the lower level of invasion to macrophage-like cells observed when the stg fimbrial cluster was overexpressed. Nevertheless, since other CU fimbrial structures increase the entry of S. Typhi into macrophages, and considering that transcriptomic analyses revealed that stg operon is indeed expressed in macrophages, we reassessed the role of the stg operon in the interaction between S. Typhi strain STH2370 and human cells, including macrophage-like cells and mononuclear cells directly taken from human peripheral blood. RESULTS: We compared S. Typhi STH2370 WT, a Chilean clinical strain, and the S. Typhi STH2370 Deltastg mutant with respect to association and invasion using epithelial and macrophage-like cells. We observed that deletion of stg operon reduced the association and invasion of S. Typhi, in both cellular types. The presence of the cloned stg operon restored the WT phenotype in all the cases. Moreover, we compared Salmonella enterica sv. Typhimurium 14028s (S. Typhimurium, a serovar lacking stg operon) and S. Typhimurium heterologously expressing S. Typhi stg. We found that the latter presents an increased cell disruption of polarized epithelial cells and an increased association in both epithelial and macrophage-like cells. CONCLUSIONS: S. Typhi stg operon encodes a functional adhesin that participates in the interaction bacteria-eukaryotic cells, including epithelial cells and macrophages like cells. The phenotypes associated to stg operon include increased association and consequent invasion in bacteria-eukaryotic cells, and cell disruption. PMID- 26149382 TI - Mixed behavior of p-phenylenediaminium guest binding with the inverted cucurbit[6]uril host. AB - The binding interaction between inverted cucurbit[6]uril (iQ[6]) and p phenylenediaminium both in the solid state and in aqueous solution has been investigated by X-ray crystallography, (1)H NMR spectroscopy and isothermal titration calorimetry (ITC). The experimental results suggest that the binding interaction between iQ[6] and p-phenylenediaminium may generate two different types of complexes in the solid state: one is an inclusion structure and the other is a sandwich structure. In aqueous solution, the iQ[6] host has an ability to accommodate the p-phenylenediaminium guest and in-out guest exchange is fast on the NMR time scale. ITC data indicate that the complexation of iQ[6] with p phenylenediaminium is entropy driven. PMID- 26149383 TI - Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project. AB - PURPOSE: Studies on drug utilization usually do not allow direct cross-national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases. METHODS: Crude and standardized prevalence rates of drug prescribing from 2001-2009 were calculated in databases from Spain, United Kingdon (UK), The Netherlands, Germany and Denmark. Prevalence was stratified by age, sex, BZD type [(using ATC codes), i.e. BZD-anxiolytics BZD-hypnotics, BZD-related drugs and clomethiazole], indication and number of prescription. RESULTS: Crude prevalence rates of BZDs prescribing ranged from 570 to 1700 per 10,000 person-years over the study period. Standardization by age and sex did not substantially change the differences. Standardized prevalence rates increased in the Spanish (+13%) and UK databases (+2% and +8%) over the study period, while they decreased in the Dutch databases (-4% and -22%), the German (-12%) and Danish (-26%) database. Prevalence of anxiolytics outweighed that of hypnotics in the Spanish, Dutch and Bavarian databases, but the reverse was shown in the UK and Danish databases. Prevalence rates consistently increased with age and were two-fold higher in women than in men in all databases. A median of 18% of users received 10 or more prescriptions in 2008. CONCLUSION: Although similar methods were applied, the prevalence of BZD prescribing varied considerably across different populations. Clinical factors related to BZDs and characteristics of the databases may explain these differences. PMID- 26149385 TI - Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins. AB - A special group of mitochondrial outer membrane (MOM) proteins spans the membrane several times via multiple helical segments. Such multispan proteins are synthesized on cytosolic ribosomes before their targeting to mitochondria and insertion into the MOM. Previous work recognized the import receptor Tom70 and the mitochondrial import (MIM) complex, both residents of the MOM, as required for optimal biogenesis of these proteins. However, their involvement is not sufficient to explain either the entire import pathway or its regulation. To identify additional factors that are involved in the biogenesis of MOM multispan proteins, we performed complementary high-throughput visual and growth screens in Saccharomyces cerevisiae. Cardiolipin (CL) synthase (Crd1) appeared as a candidate in both screens. Our results indeed demonstrate lower steady-state levels of the multispan proteins Ugo1, Scm4, and Om14 in mitochondria from crd1Delta cells. Importantly, MOM single-span proteins were not affected by this mutation. Furthermore, organelles lacking Crd1 had a lower in vitro capacity to import newly synthesized Ugo1 and Scm4 molecules. Crd1, which is located in the mitochondrial inner membrane, condenses phosphatidylglycerol together with CDP diacylglycerol to obtain de novo synthesized CL molecules. Hence, our findings suggest that CL is an important component in the biogenesis of MOM multispan proteins. PMID- 26149384 TI - Ezrin Binds to DEAD-Box RNA Helicase DDX3 and Regulates Its Function and Protein Level. AB - Ezrin is a key regulator of cancer metastasis that links the extracellular matrix to the actin cytoskeleton and regulates cell morphology and motility. We discovered a small-molecule inhibitor, NSC305787, that directly binds to ezrin and inhibits its function. In this study, we used a nano-liquid chromatography tandem mass spectrometry (nano-LC-MS-MS)-based proteomic approach to identify ezrin-interacting proteins that are competed away by NSC305787. A large number of the proteins that interact with ezrin were implicated in protein translation and stress granule dynamics. We validated direct interaction between ezrin and the RNA helicase DDX3, and NSC305787 blocked this interaction. Downregulation or long term pharmacological inhibition of ezrin led to reduced DDX3 protein levels without changes in DDX3 mRNA. Ectopic overexpression of ezrin in low-ezrin expressing osteosarcoma cells caused a notable increase in DDX3 protein levels. Ezrin inhibited the RNA helicase activity of DDX3 but increased its ATPase activity. Our data suggest that ezrin controls the translation of mRNAs preferentially with a structured 5' untranslated region, at least in part, by sustaining the protein level of DDX3 and/or regulating its function. Therefore, our findings suggest a novel function for ezrin in regulation of gene translation that is distinct from its canonical role as a cytoskeletal scaffold at the cell membrane. PMID- 26149386 TI - Regulation of Transcription Elongation by the XPG-TFIIH Complex Is Implicated in Cockayne Syndrome. AB - XPG is a causative gene underlying the photosensitive disorder xeroderma pigmentosum group G (XP-G) and is involved in nucleotide excision repair. Here, we show that XPG knockdown represses epidermal growth factor (EGF)-induced FOS transcription at the level of transcription elongation with little effect on EGF signal transduction. XPG interacted with transcription elongation factors in concert with TFIIH, suggesting that the XPG-TFIIH complex serves as a transcription elongation factor. The XPG-TFIIH complex was recruited to promoter and coding regions of both EGF-induced (FOS) and housekeeping (EEF1A1) genes. Further, EGF-induced recruitment of RNA polymerase II and TFIIH to FOS was reduced by XPG knockdown. Importantly, EGF-induced FOS transcription was markedly lower in XP-G/Cockayne syndrome (CS) cells expressing truncated XPG than in control cells expressing wild-type (WT) XPG, with less significant decreases in XP-G cells with XPG nuclease domain mutations. In corroboration of this finding, both WT XPG and a missense XPG mutant from an XP-G patient were recruited to FOS upon EGF stimulation, but an XPG mutant mimicking a C-terminal truncation from an XP-G/CS patient was not. These results suggest that the XPG-TFIIH complex is involved in transcription elongation and that defects in this association may partly account for Cockayne syndrome in XP-G/CS patients. PMID- 26149387 TI - LIN28A Modulates Splicing and Gene Expression Programs in Breast Cancer Cells. AB - LIN28 is an evolutionarily conserved RNA-binding protein with critical functions in developmental timing and cancer. However, the molecular mechanisms underlying LIN28's oncogenic properties are yet to be described. RNA-protein immunoprecipitation coupled with genome-wide sequencing (RIP-Seq) analysis revealed significant LIN28 binding within 843 mRNAs in breast cancer cells. Many of the LIN28-bound mRNAs are implicated in the regulation of RNA and cell metabolism. We identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a protein with multiple roles in mRNA metabolism, as a LIN28-interacting partner. Subsequently, we used a custom computational method to identify differentially spliced gene isoforms in LIN28 and hnRNP A1 small interfering RNA (siRNA)-treated cells. The results reveal that these proteins regulate alternative splicing and steady-state mRNA expression of genes implicated in aspects of breast cancer biology. Notably, cells lacking LIN28 undergo significant isoform switching of the ENAH gene, resulting in a decrease in the expression of the ENAH exon 11a isoform. The expression of ENAH isoform 11a has been shown to be elevated in breast cancers that express HER2. Intriguingly, analysis of publicly available array data from the Cancer Genome Atlas (TCGA) reveals that LIN28 expression in the HER2 subtype is significantly different from that in other breast cancer subtypes. Collectively, our data suggest that LIN28 may regulate splicing and gene expression programs that drive breast cancer subtype phenotypes. PMID- 26149388 TI - Dynamic Regulation of AP-1 Transcriptional Complexes Directs Trophoblast Differentiation. AB - Placentation is a process that establishes the maternal-fetal interface and is required for successful pregnancy. The epithelial component of the placenta consists of trophoblast cells, which possess the capacity for multilineage differentiation and are responsible for placenta-specific functions. FOS-like antigen 1 (FOSL1), a component of AP-1 transcription factor complexes, contributes to the regulation of placental development. FOSL1 expression is restricted to trophoblast giant cells and invasive trophoblast cells. In the present study, we characterized the FOSL1 regulatory pathway in rat trophoblast cells. Transcriptome profiling in control and FOSL1 knockdown cells identified FOSL1-dependent gene sets linked to endocrine and invasive functions. FOSL1 was shown to occupy AP-1 binding sites within these gene loci, as determined by chromatin immunoprecipitation (ChIP). Complementary in vivo experiments using trophoblast-specific lentiviral delivery of FOSL1 short hairpin RNAs (shRNAs) provided in vivo validation of FOSL1 targets. FOSL1 actions require a dimerization partner. Coimmunoprecipitation, coimmunolocalization, and ChIP analyses showed that FOSL1 interacts with JUNB and, to a lesser extent, JUN in differentiating trophoblast cells. Knockdown of FOSL1 and JUNB expression inhibited both endocrine and invasive properties of trophoblast cells. In summary, FOSL1 recruits JUNB to form AP-1 transcriptional complexes that specifically regulate the endocrine and invasive trophoblast phenotypes. PMID- 26149389 TI - PU.1-Regulated Long Noncoding RNA lnc-MC Controls Human Monocyte/Macrophage Differentiation through Interaction with MicroRNA 199a-5p. AB - Long noncoding RNAs (lncRNAs) are emerging as important regulators in mammalian development, but little is known about their roles in monocyte/macrophage differentiation. Here we identified a long noncoding monocytic RNA (lnc-MC) that exhibits increased expression during monocyte/macrophage differentiation of THP-1 and HL-60 cells as well as CD34(+) hematopoietic stem/progenitor cells (HSPCs) and is transcriptionally activated by PU.1. Gain- and loss-of-function assays demonstrate that lnc-MC promotes monocyte/macrophage differentiation of THP-1 cells and CD34(+) HSPCs. Mechanistic investigation reveals that lnc-MC acts as a competing endogenous RNA to sequester microRNA 199a-5p (miR-199a-5p) and alleviate repression on the expression of activin A receptor type 1B (ACVR1B), an important regulator of monocyte/macrophage differentiation. We also noted a repressive effect of miR-199a-5p on lnc-MC expression and function, but PU.1 dominant downregulation of miR-199a-5p weakens the role of miR-199a-5p in the reciprocal regulation between miR-199a-5p and lnc-MC. Altogether, our work demonstrates that two PU.1-regulated noncoding RNAs, lnc-MC and miR-199a-5p, have opposing roles in monocyte/macrophage differentiation and that lnc-MC facilitates the differentiation process, enhancing the effect of PU.1, by soaking up miR-199a 5p and releasing ACVR1B expression. Thus, we reveal a novel regulatory mechanism, comprising PU.1, lnc-MC, miR-199a-5p, and ACVR1B, in monocyte/macrophage differentiation. PMID- 26149391 TI - Influence of proximal drug eluting stent (DES) on distal bare metal stent (BMS) in multi-stent implantation strategies in coronary arteries. AB - The aim of this study was to investigate the drug distribution in arteries treated with DES-BMS stenting strategy and to analyze the influence of proximal DES on distal segments of BMS. A straight artery model (Straight Model) and a branching artery model (Branching Model) were constructed in this study. In each model, the DES was implanted at the proximal position and the BMS was implanted distally. Hemodynamic environments, drug delivery and distribution features were simulated and analyzed in each model. The results showed that blood flow would contribute to non-uniform drug distribution in arteries. In the Straight Model the proximal DES would cause drug concentration in BMS segments. While in the Branching Model the DES in the main artery has slight influence on the BMS segments in the branch artery. In conclusion, due to the blood flow washing effect the uniformly released drug from DES would distribute focally and distally. The proximal DES would have greater influence on the distal BMS in straight artery than that in branching artery. This preliminary study would provide good reference for atherosclerosis treatment, especially for some complex cases, like coronary branching stenting. PMID- 26149390 TI - ARTD1 Suppresses Interleukin 6 Expression by Repressing MLL1-Dependent Histone H3 Trimethylation. AB - ADP-ribosyltransferase diphtheria-toxin like 1/poly(ADP-ribose) polymerase 1 (ARTD1/PARP1) is a chromatin-associated protein in the nucleus and plays an important role in different cellular processes such as regulation of gene transcription. ARTD1 has been shown to coregulate the inflammatory response by modulating the activity of the transcription factor nuclear factor kappaB (NF kappaB), the principal regulator of interleukin 6 (IL-6), an important inflammatory cytokine implicated in a variety of diseases such as cancer. However, to what extent and how ARTD1 regulates IL-6 transcription has not been clear. Here, we show that ARTD1 suppresses lipopolysaccharide (LPS)-induced IL-6 expression in macrophages, without affecting the recruitment of the NF-kappaB subunit RelA to the IL-6 promoter and independent of its enzymatic activity. Interestingly, knockdown of ARTD1 did not alter H3 occupancy but increased LPS induced trimethylation of histone 3 at lysine 4 (H3K4me3), a hallmark of transcriptionally active genes. We found that ARTD1 mediates its effect through the methyltransferase MLL1, by catalyzing H3K4me3 at the IL-6 promoter and forming a complex with NF-kappaB. These results demonstrate that ARTD1 modulates IL-6 expression by regulating the function of an NF-kappaB enhanceosome complex, which involves MLL1 and does not require ADP-ribosylation. PMID- 26149392 TI - Prostate Cancer in the Arab World: A View From the Inside. AB - The rates of prostate cancer vary by more than 50-fold across different international populations. The aim of this review was to explore the differences in epidemiology and risk factors between the Middle Eastern Arab countries and some of the developed countries in Europe and North America. The age-standardized incidence rate of prostate cancer in the Arab countries is still lower than that in the Western countries, but is steadily increasing with time. Several factors come into play to explain this difference. There are health care systems-related factors such as the lack of good population-based registries, and population related factors. The latter include the relatively young age structure in the Arab countries, lower reported androgen and prostate-specific antigen levels in Arab men, the effect of genetic differences on prostate cancer risk, the metabolic syndrome paradox, and the protective effect of the Mediterranean diet on a subset of the Arab population. In conclusion, the study of prostate cancer in the Arab world represents a challenge with the currently available cancer care systems and the increase in the burden of the disease. A multinational prospective study to investigate the epidemiology of prostate cancer in the Middle East, with specific attention to country/geographic variability along with a comparative analysis to that of the Western hemisphere is needed. PMID- 26149393 TI - Relationship between optimism and quality of life in patients with two chronic rheumatic diseases: axial spondyloarthritis and chronic low back pain: a cross sectional study of 288 patients. AB - BACKGROUND: Axial Spondyloarthritis (AxSpA) and chronic low back pain are rheumatic diseases that impact patients' health-related quality of life (HRQoL). In other chronic conditions, HRQoL was positively associated with dispositional optimism, a personality trait. The objective was to explore the relationship between optimism and HRQoL in these two diseases. METHOD: A cross-sectional study was performed in 2 tertiary care hospitals and 2 private practices in France. Patients had definite AxSpA or chronic low back pain according to the rheumatologist. A generic HRQoL questionnaire (Short Form, SF-12) with physical and mental composite scores (PCS and MCS respectively) and an optimism questionnaire (the Life Orientation Test-revised, LOT-R) were collected. Analyses included non-parametric correlations and multiple regression analyses to study the effect of optimism on PCS and MCS. RESULTS: In all, 288 (199 AxSpA and 89 low back pain) patients were included: mean age, 47.3 +/- 11.9 years, 48.6 % were males. Pain levels (0-10) were 4.5 +/- 2.4 and 4.3 +/- 2.4 in AxSpA and LOW BACK PAIN patients, respectively. HRQoL was similarly altered in both diseases, for both physical and mental composite scores (mean PCS: 43.7 +/- 8.2 vs. 41.9 +/- 7.1; mean MCS: 45.9 +/- 7.8 vs. 46.7 +/- 8.1 for AxSpA and low back pain respectively). Optimism was moderate and similar in both populations. Optimism was positively correlated to MCS in both diseases (rho = 0.54 and 0.58, respectively, both p <0.01) and these relations persisted in multivariate analyses (beta = 1.03 and 1.40, both p <0.0001). CONCLUSIONS: Optimism was similar in these 2 chronic diseases and was an explanatory factor of the mental component of HRQoL, but not physical HRQoL. Physical HRQoL may reflect more the disease process than character traits. PMID- 26149395 TI - Probability and Visual Aids for Assessing Intervention Effectiveness in Single Case Designs: A Field Test. AB - Single-case data analysis still relies heavily on visual inspection, and, at the same time, it is not clear to what extent the results of different quantitative procedures converge in identifying an intervention effect and its magnitude when applied to the same data; this is the type of evidence provided here for two procedures. One of the procedures, included due to the importance of providing objective criteria to visual analysts, is a visual aid fitting and projecting split-middle trend while taking into account data variability. The other procedure converts several different metrics into probabilities making their results comparable. In the present study, we expore to what extend these two procedures coincide in the magnitude of intervention effect taking place in a set of studies stemming from a recent meta-analysis. The procedures concur to a greater extent with the values of the indices computed and with each other and, to a lesser extent, with our own visual analysis. For distinguishing smaller from larger effects, the probability-based approach seems somewhat better suited. Moreover, the results of the field test suggest that the latter is a reasonably good mechanism for translating different metrics into similar labels. User friendly R code is provided for promoting the use of the visual aid, together with a quantification based on nonoverlap and the label provided by the probability approach. PMID- 26149394 TI - Long-term health-related quality of life of living kidney donors: a single-center experience. AB - PURPOSE: Over the last few years, the evaluation of the health-related quality of life (HRQoL) of living kidney donors (LKD) has become of particular interest. The present study sought to evaluate the physical and mental HRQoL after kidney removal. The clinical and paraclinical course of these patients was examined, and the impact of preoperative donor evaluation, donor nephrectomy, and surgical recovery was evaluated. These data were compared with reference data of the general population. METHODS: Between 1998 and 2010, 72 living kidney donations were performed at our institution. To assess the HRQoL, two questionnaires-the Short Form 36 (SF-36) and a special LKD questionnaire-were sent to all 72 living donors. The records of the follow-up examinations of all 72 donors were retrospectively analyzed in order to assess the clinical and paraclinical data after kidney donation. RESULTS: Out of 72 donors, 55 (76.4 %) responded to the questionnaires. There was no change in systolic and diastolic blood pressure during the 7-year follow-up (p > 0.05). Mild proteinuria (>150 mg/l) was observed in six cases. Kidney donors had a higher HRQoL compared to the general population with mean values of the physical and mental summation scale (PCS and MCS, respectively) being 51.3 (SD = 7.6) and 50.6 (SD = 8.1). Peri- or postoperative complications were associated with lower values for physical function and physical component summary (PCS) (p < 0.05). DISCUSSION: Living donor kidney transplantation appears to be safe for donors. The HRQoL is excellent. To ensure a positive outcome for donors, a good clinical evaluation of potential donors is essential. PMID- 26149397 TI - Spectroscopic insights into the Photoreduction of Cytochrome c with UVA-Vis Light Irradiation. AB - With the particular conjugation structure in the heme prosthetic group, Cyt c shows unusual functions similar to chlorophyll while irradiated by specific wavelength of UV-Vis lights. To further reveal mechanism of the photo-irradiation of Cyt c, we then studied various external factors that may influence the photo induced process. The absorbance intensity increase of band (317 nm) and Q band (520 nm and 549 nm)indicated Cyt c in phosphate-buffered saline within N2 atmosphere was photoreduced to Fe(II) Cyt c. Irradiated by 410 nm, the photoreduction process was facilitated by Met. But Trp, Tyr and Phe impeded the process due to their light absorbance abilities. In addition, the results of fluorescence and CD spectra indicated that the microenvironment polarity of Trp residue varied during the photoreduction process. And the secondary structure of Cyt c changed with lower alpha-helix/betasheet ratio. The photoreduction mechanism of Cyt c was intramolecular electron transfer and porphyrin cation radicals were generated. The protein structure of Cyt c changed as well as part of the photoreduction. PMID- 26149396 TI - Assessing protein energy wasting in a Malaysian haemodialysis population using self-reported appetite rating: a cross-sectional study. AB - BACKGROUND: Poor appetite could be indicative of protein energy wasting (PEW) and experts recommend assessing appetite in dialysis patients. Our study aims to determine the relationship between PEW and appetite in haemodialysis (HD) patients. METHODS: HD patients (n=205) self-rated their appetite on a scale of 1 to 5 as very good (1), good (2), fair (3), poor (4) or very poor (5). Nutritional markers were compared against appetite ratings. Using logistic regression analysis associations between dichotomized appetite with PEW diagnosis were determined as per the International Society of Renal Nutrition and Metabolism (ISRNM) criteria and alternate objective measures. Data was adjusted for socioeconomic and demographic characteristics. RESULTS: Poorer appetite ratings were significantly associated with lower income (P = 0.021), lower measurements (P < 0.05) for mid-arm muscle circumference, mid-arm muscle area and lean tissue mass (LTM), serum urea (P = 0.007) and creatinine (P = 0.005). The highest hsCRP (P = 0.016) levels occurred in patients reporting the poorest appetite. Serum albumin did not differ significantly across appetite ratings. Poor oral intake represented by underreporting (EI/BMR < 1.2) was evident for all appetite ratings. PEW was prevalent irrespective of appetite ratings (very good: 17.6 %, good: 40.2 %, fair: 42.3 % and poor: 83.3 %). After dichotomizing appetite ratings into normal and diminished categories, there was a marginal positive association between diminished appetite and overall PEW diagnosis (OR adj: 1.71; 95 % CI: 0.94-3.10, P = 0.079). Amongst individual ISRNM criteria, only BMI < 23 kg/m2 was positively associated with diminished appetite (OR adj: 2.17; 95 % CI: 1.18-3.99). However, patients reporting diminished appetite were more likely to have lower LTM (OR adj: 2.86; 95 % CI: 1.31-6.24) and fat mass (OR adj: 1.91; 95 % CI: 1.03-3.53), lower levels of serum urea (OR adj: 2.74; 95 % CI: 1.49-5.06) and creatinine (OR adj: 1.99; 95 % CI: 1.01-3.92), higher Dialysis Malnutrition Score (OR adj: 2.75; 95 % CI: 1.50-5.03), Malnutrition Inflammation Score (OR adj: 2.15; 95 % CI: 1.17-3.94), and poorer physical (OR adj: 3.49; 95 % CI: 1.89 6.47) and mental (OR adj: 5.75; 95 % CI: 3.02-10.95) scores. CONCLUSIONS: A graded but non-significant increase in the proportion of PEW patients occurred as appetite became poorer. However, after dichotomization, a positive but marginally significant association was observed between diminished appetite and PEW diagnosis. PMID- 26149399 TI - Purification and Characterization of a Thermostable Caseinolytic Serine Protease from the Latex of Euphorbia heterophylla L. AB - A new thermostable caseinolytic serine protease was purified from the latex of Euphorbia heterophylla L. to electrophoretic homogeneity by a procedure involving successive steps of pretreatment of the latex, PEG fractionation, CM-cellulose chromatography and DEAE-cellulose chromatography. The purified protease was found to be a monomeric protein of molecular weight 77.2 kDa. It exhibited caseinolytic activity with hyperbolic azocasein saturation with Vmax and Km values of 0.11 units.mL(-1) and 0.55 mg.mL(-1) respectively. Specific inhibitory studies revealed the enzyme to be a serine protease. The protease was characterized by pH optimum of 8.0 and high thermostability with T1/2 of 75 degrees C. Based on the results of peptide mass fingerprinting analysis, the protease was shown to be a new protein not characterized earlier. PMID- 26149400 TI - Thioredoxin from Escherichia coli as a Role Model of Molecular Recognition, Folding, Dynamics and Function. AB - Thioredoxin (TRX) catalyzes redox reactions via the reversible oxidation of the conserved active center CGPC and it is involved in multiple biological processes, some of them linked to redox activity while others not. TRX is a globular, thermodynamically stable and monomeric alpha/beta protein with a structure characterized by a central beta-sheet surrounded by alpha-helices. In this review we discuss central aspects of folding, dynamics and function of Escherichia coli TRX (EcTRX), pointing to the characterization of the full-length protein and of relevant fragments. In addition, we focus on the critical role that the C terminal alpha-helical element plays in a late event in the consolidation of the overall EcTRX fold. Furthermore, we address the characterization of internal molecular motions by NMR and molecular dynamics simulation techniques. Finally, we review important aspects of the relationship among structure, dynamics and enzymatic function of this key redox protein. PMID- 26149401 TI - The adequacy of Hepato-Pancreato-Biliary training: how closely do perceptions of fellows and programme directors align? AB - BACKGROUND: Hepatopancreatobiliary fellowship programmes have recently undergone significant changes with regards to training standards, case-volume thresholds and multimodality educational platforms. The goals of this study were to compare the perspectives of fellows and programme directors (PDs) on perceptions of readiness to enter practice and identify core Hepato-Pancreato-Biliary (HPB) procedures that require increased emphasis during training. METHODS: This survey targeted PDs and trainees participating in the Fellowship Council/AHPBA pathway. Data related to demographics, education and career plans were collected. Analysis of PD and fellow opinions regarding their confidence to perform core HPB procedures was completed. RESULTS: The response rate was 88% for both fellows (21/24) and PDs (23/26). There was good agreement between PDs and fellows in the perception of case volumes. Select differences where PDs ranked higher perceptions included major hepatectomies (PDs: 87% versus fellows: 57%, P = 0.04), pancreaticoduodenectomies (100% versus 81%, P = 0.04) and laparoscopic distal pancreatectomies (78% versus 43%, P = 0.03). 'Good or excellent' case volumes translated into increased fellow readiness, except for some pancreatitis procedures, laparoscopic distal pancreatectomies and potentially major hepatectomies. CONCLUSIONS: This study provides insight into content domains that may require additional attention to achieve an appropriate level of proficiency and confidence upon completion of training. PMID- 26149402 TI - Brain functional plasticity at rest and during action in multiple sclerosis patients. AB - We aimed to demonstrate that basal functional connectivity reorganization observed in a specific network at rest using resting state functional MRI (rs fMRI) could be associated with functional cortical reorganization in such network during action (ta-fMRI) in a population of early multiple sclerosis (MS) patients. Altered basal functional connectivity has been previously reported in patients with MS but relationships with cortical reorganization during action have not been explored. Thirteen patients with early relapsing-remitting MS and 14 matched healthy controls were explored on a 3T MRI scanner at rest and during a motor task (conjugate finger flexion and extension movements of each hand). Hand motor networks were extracted from rs-fMRI data using group spatial independent component analysis. For the non-dominant motor network, patients presented a higher basal functional connectivity at rest and recruited a supplementary prefrontal cortical area during action compared to the controls. The levels of hyperconnectivity at rest and of activation in the recruited area during action were significantly correlated. No differences were demonstrated for the dominant motor network at rest and during action. The present study, combining rs-fMRI and ta-fMRI in non-disabled patients with early MS, revealed for the first time a direct association between functional reorganization depicted at rest and during action within the same system. PMID- 26149403 TI - Elevated relative risk of aneurysmal subarachnoid hemorrhage with colder weather in the mid-Atlantic region. AB - We have previously reported an increase of 0.6% in the relative risk of aneurysmal subarachnoid hemorrhage (aSAH) in response to every 1 degrees F decrease in the maximum daily temperature (Tmax) in colder seasons from patients presenting to our regional tertiary care center. We hypothesized that this relationship would also be observed in the warmer summer months with ambient temperatures greater than 70 degrees F. From prospectively collected incidence data for aSAH patients, we investigated absolute Tmax, average daily temperatures, intraday temperature ranges, and the variation of daily Tmax relative to 70 degrees F to assess associations with aSAH incidence for patients admitted to our institution between 1991 and 2009 during the hottest months and days on which Tmax>70 degrees F. For all days treated as a group, the mean Tmax (+/- standard deviation) was lower when aSAH occurred than when it did not (64.4+/-18.2 degrees F versus 65.8+/-18.3 degrees F; p=0.016). During summer months, the odds ratio (OR) of aSAH incidence increased with lower mean Tmax (OR 1.019; 95% confidence interval 1.001-1.037; p=0.043). The proportion of days with aSAH admissions was lower on hotter days than the proportion of days with no aSAH (96% versus 98%; p=0.006). aSAH were more likely to occur during the summer and on days with a temperature fluctuation less than 10 degrees F (8% versus 4%; p=0.002). During the hottest months of the year in the mid-Atlantic region, colder maximum daily temperatures, a smaller heat burden above 70 degrees F, and smaller intraday temperature fluctuations are associated with increased aSAH admissions in a similar manner to colder months. These findings support the hypothesis that aSAH incidence is more likely with drops in temperature, even in the warmer months. PMID- 26149404 TI - Treatment with escitalopram improves the attentional bias toward negative facial expressions in patients with major depressive disorders. AB - We hypothesized that treatment with escitalopram would improve cognitive bias and contribute to the recovery process for patients with major depressive disorder (MDD). Many previous studies have established that patients with MDD tend to pay selective attention to negative stimuli. The assessment of the level of cognitive bias is regarded as a crucial dimension of treatment outcomes for MDD. To our knowledge, no prior studies have been reported on the effects of treatment with escitalopram on attentional bias in MDD, employing a dot probe task of facial expression. We studied 25 patients with MDD and 25 controls, and used a dot probe task of facial expression to measure cognitive bias. The patients' psychopathologies were rated using the Hamilton Depression Scale (HAMD) at baseline and after 8 weeks of treatment with escitalopram. All participants performed the facial expression dot probe task. The results revealed that the 8 week escitalopram treatment decreased the HAMD scores. The patients with MDD at baseline exhibited an attentional bias towards negative faces, however, no significant bias toward either negative or happy faces were observed in the controls. After the 8 week escitalopram treatment, no significant bias toward negative faces was observed in the patient group. In conclusion, patients with MDD pay more attention to negative facial expressions, and treatment with escitalopram improves this attentional bias toward negative facial expressions. This is the first study, to our knowledge, on the effects of treatment with escitalopram on attentional bias in patients with MDD that has employed a dot probe task of facial expression. PMID- 26149405 TI - Stand-alone anterior lumbar interbody fusion for treatment of degenerative spondylolisthesis. AB - We sought to evaluate the clinical and radiologic efficacy of stand-alone anterior lumbar interbody fusion (ALIF) for low grade degenerative spondylolisthesis, the favoured surgical management approach at our institution. The optimal approach for surgical management of spondylolisthesis remains contentious. We performed a prospective analysis of all consecutive patients with low grade lumbar spondylolisthesis who underwent ALIF between 2009 and 2013 by a single surgeon (n=27). The mean age was 64.9 years with a male to female ratio of 14:13. There were 32 levels operated and the average preoperative spondylolisthesis was 14.8%, which reduced to 6.4% postoperatively and 9.4% at the latest follow-up (p=0001). Postoperative disc height was increased to 175% of preoperative values and was statistically significant (p<0.001) and remained improved with an overall change of 139% at the latest follow-up. The radiological fusion rate was 91%. The 12-Item Short Form Health Survey (SF-12) mental and physical component summary improved from 31.7 to 43.0 (p=0.007) and from 35.4 to 51.7 (p=0.0026), respectively. The mean visual analogue scale pain score improved from 7.6 to 2.2 (p<0.001), and the mean Oswestry disability index improved from 56.9 to 17.8% (p<0.0001). The overall clinical success rate was 93%. The posterior disc height correlated with spondylolisthesis reduction (p=0.04) and the only clinical factor affecting reduction was body mass index (p=0.04). The present study provides encouraging short term results for stand-alone ALIF as a procedure for low grade lumbar degenerative spondylolisthesis. Future studies should include adequately powered, prospective, multicentre registry studies with long term follow-up to allow a better assessment of the relative benefits and risks. PMID- 26149406 TI - Olfactory abnormalities in temporal lobe epilepsy. AB - We studied olfactory function in a cohort of 25 temporal lobe epilepsy (TLE) patients and 25 healthy controls. Our objectives were to measure olfactory acuity in patients with right, left or bilateral TLE and compare them with age and sex matched controls, and to correlate olfactory acuity with duration of seizure, baseline seizure control and the number of drugs used. Olfactory impairment is common in neurological disorders and dysfunction of the temporo-limbic neural substrates involved in olfactory perception is noted in TLE. We measured olfactory acuity in 25 patients with TLE, nine with right, 10 with left and six with bilateral temporal lobe seizure activity, and compared them to the controls. Odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) which is a 40 item olfactory test used to diagnose olfactory deficits. Our results showed that patients with TLE exhibited significant impairment in UPSIT performance compared to the controls. There was no significant difference in scores between the right and left TLE patients. The severity of olfactory impairment did not correlate with the duration of seizures, baseline seizure control and number of drugs used. We concluded that significant olfactory impairment is seen in both right and left TLE patients, unrelated to the duration and baseline frequency of seizures or drugs used. PMID- 26149407 TI - Use of the de novo transcriptome analysis of silver-leaf nightshade (Solanum elaeagnifolium) to identify gene expression changes associated with wounding and terpene biosynthesis. AB - BACKGROUND: Solanum elaeagnifolium, an invasive weed of the Solanaceae family, is poorly studied although it poses a significant threat to crops. Here the analysis of the transcriptome of S. elaeagnifolium is presented, as a means to explore the biology of this species and to identify genes related to its adaptation to environmental stress. One of the basic mechanisms by which plants respond to environmental stress is through the synthesis of specific secondary metabolites that protect the plant from herbivores and microorganisms, or serve as signaling molecules. One important such group of secondary metabolites are terpenes. RESULTS: By next-generation sequencing, the flower/leaf transcriptome of S. elaeagnifolium was sequenced and de novo assembled into 75,618 unigenes. Among the unigenes identified, several corresponded to genes involved in terpene biosynthesis; these included terpene synthases (TPSs) and genes of the mevalonate (MVA) and the methylerythritol phosphate (MEP) pathways. Functional characterization of two of the TPSs showed that one produced the sesquiterpene (E)-caryophyllene and the second produced the monoterpene camphene. Analysis of wounded S. elaeagnifolium leaves has shown significant increase of the concentration of (E)-caryophyllene and geranyl linalool, two terpenes implicated in stress responses. The increased production of (E)-caryophyllene was matched to the induced expression of the corresponding TPS gene. Wounding also led to the increased expression of the putative 1-deoxy-D-xylulose-5-phosphate synthase 2 (DXS2) gene, a key enzyme of the MEP pathway, corroborating the overall increased output of terpene biosynthesis. CONCLUSIONS: The reported S. elaeagnifolium de novo transcriptome provides a valuable sequence database that could facilitate study of this invasive weed and contribute to our understanding of the highly diverse Solanaceae family. Analysis of genes and pathways involved in the plant's interaction with the environment will help to elucidate the mechanisms that underly the intricate features of this unique Solanum species. PMID- 26149408 TI - Herbal hepatotoxicity: current status, examples, and challenges. AB - INTRODUCTION: Herbal medicines have commonly been considered safe by the general public due to their natural origin and long history of traditional uses. In contrast to this belief, many plants produce toxic substances as secondary metabolites that are sometimes not easily distinguishable from the pharmacological active compounds. Some herbal medicines have been associated with adverse effects and toxic effects, including hepatotoxicity, which have been reversed upon discontinuation of the herbal medicine by the patient. AREAS COVERED: This review reflects on selected herbal medicines that are associated with hepatotoxic effects including a description of the phytochemicals that have been linked to liver injury where available. Although case studies are discussed where patients presented with hepatotoxicity due to use of herbal medicines, results from both in vitro and in vivo studies that have been undertaken to confirm liver injury are also included. EXPERT OPINION: Increasing evidence of herbal hepatotoxicity has become available through case reports; however, several factors contribute to challenges associated with causality assessment and pre emptive testing as well as diagnosis of herb-induced liver injury. PMID- 26149409 TI - BCR-ABL1 e6a2 transcript in chronic myeloid leukemia: biological features and molecular monitoring by droplet digital PCR. AB - The BCR-ABL1 fusion on the Philadelphia (Ph) chromosome is a hallmark of chronic myeloid leukemia (CML). More than 95 % of BCR-ABL1 transcripts in CML are either e13a2 or e14a2 (major breakpoint cluster region or M-bcr), whereas rare BCR-ABL1 transcripts are occasionally observed, accounting for less than 1 % of CML cases. Among these, a very rare fusion transcript joining the first 6 exons of BCR to exon 2 of ABL1 (e6a2) has been reported in various hematological malignancies characterized by an aggressive clinical course. We report a new case of blast crisis (BC) CML with an e6a2 fusion transcript characterized by many eosinophil precursors with abnormal granules. Moreover, fluorescence in situ hybridization analysis revealed genomic deletions of 1.3 megabases and 342 kilobases on der(9) of chromosome 9 and 22 sequences, respectively. The fusion transcript was quantified at diagnosis and during follow-up using digital droplet polymerase chain reaction (ddPCR) technology. The patient was treated with Dasatinib (140 mg/day), resulting in a 3-log reduction of the e6a2 transcript molecular burden from the third month after treatment. In this twentieth e6a2 case, characterized by marked eosinophilic dysplasia, deletions on der(9), and responsive to tyrosine kinase inhibitors therapy, we demonstrate that for molecular response monitoring of rare fusion transcripts associated with CML, ddPCR is a very useful technology. PMID- 26149410 TI - A risk screening tool for ethical appraisal of evidence-generating initiatives. AB - BACKGROUND: The boundaries between health-related research and practice have become blurred as initiatives traditionally considered to be practice (e.g., quality improvement, program evaluation) increasingly use the same methodology as research. Further, the application of different ethical requirements based on this distinction raises concerns because many initiatives commonly labelled as "non-research" are associated with risks to patients, participants, and other stakeholders, yet may not be subject to any ethical oversight. Accordingly, we sought to develop a tool to facilitate the systematic identification of risks to human participants and determination of risk level across a broad range of projects (e.g., clinical research, laboratory-based projects, population-based surveillance, and program evaluation) and health-related contexts. This paper describes the development of the Public Health Ontario (PHO) Risk Screening Tool. METHOD: Development of the PHO Risk Screening Tool included: (1) preparation of a draft risk tool (n = 47 items); (2) expert appraisal; (3) internal stakeholder validation; (4) external validation; (5) pilot testing and evalution of the draft tool; and (6) revision after 1 year of testing. RESULTS: A risk screening tool was generated consisting of 20 items organized into five risk domains: Sensitivity; Participant Selection, Recruitment and Consent; Data/Sample Collection; Identifiability and Privacy Risk; and Commercial Interests. The PHO Risk Screening Tool is an electronic tool, designed to identify potential project associated risks to participants and communities and to determine what level of ethics review is required, if any. The tool features an easy to use checklist format that generates a risk score (0-3) associated with a suggested level of ethics review once all items have been completed. The final score is based on a threshold approach to ensure that the final score represents the highest level of risk identified in any of the domains of the tool. CONCLUSIONS: The PHO Risk Screening Tool offers a practical solution to the problem of how to maintain accountability and appropriate risk oversight that transcends the boundaries of research and practice. We hope that the PHO Risk Screening Tool will prove useful in minimizing the problems of over and under protection across a wide range of disciplines and jurisdictions. PMID- 26149411 TI - Substance-use disorder in high-functioning autism: clinical and neurocognitive insights from two case reports. AB - BACKGROUND: Low prevalence of substance-use disorder has been reported in adults with autism. However, on a superficial level, adults with high-functioning autism (HFA) display a 'normal' facade when they drink alcohol, which may explain why their alcohol dependency is not better diagnosed. CASE PRESENTATION: Here, we report two cases of HFA adults who use alcohol and psychostimulants to cope with their anxiety and improve their cognitive abilities and social skills. We analyze how neurocognitive traits associated with HFA may be potential triggers for substance-use disorder. CONCLUSION: Better identification of autism and its cognitive impairments, which may be vulnerability traits for developing substance use disorders, could help improve the diagnosis and treatment of substance-use disorders among this population. PMID- 26149413 TI - Synthesis of diamond-like phase from graphite by ultrafast laser driven dynamical compression. AB - Rapid variations of the environmental energy caused by ultrashort laser pulses have induced phase transitions in carbon allotropes, therefore bringing the promise of revealing new carbon phases. Here, by exposing polycrystalline graphite to 25 fs laser pulses at 4 J/cm(2) fluence under standard air atmosphere, we demonstrated the synthesis of translucent micrometer-sized structures carrying diamond-like and onion-like carbon phases. Texturized domains of the diamond phase were also identified. Concerning different synthesized carbon forms, pulse superposition and singularities of the thermodynamical process, we pinpoint the synthesis mechanism by the laser-induced subsequent products energetically evolving to attain the diamond-like phase. PMID- 26149412 TI - Electron Microscopic Visualization of Protein Assemblies on Flattened DNA Origami. AB - DNA provides an ideal substrate for the engineering of versatile nanostructures due to its reliable Watson-Crick base pairing and well-characterized conformation. One of the most promising applications of DNA nanostructures arises from the site-directed spatial arrangement with nanometer precision of guest components such as proteins, metal nanoparticles, and small molecules. Two dimensional DNA origami architectures, in particular, offer a simple design, high yield of assembly, and large surface area for use as a nanoplatform. However, such single-layer DNA origami were recently found to be structurally polymorphous due to their high flexibility, leading to the development of conformationally restrained multilayered origami that lack some of the advantages of the single layer designs. Here we monitored single-layer DNA origami by transmission electron microscopy (EM) and discovered that their conformational heterogeneity is dramatically reduced in the presence of a low concentration of dimethyl sulfoxide, allowing for an efficient flattening onto the carbon support of an EM grid. We further demonstrated that streptavidin and a biotinylated target protein (cocaine esterase, CocE) can be captured at predesignated sites on these flattened origami while maintaining their functional integrity. Our demonstration that protein assemblies can be constructed with high spatial precision (within ~2 nm of their predicted position on the platforms) by using strategically flattened single-layer origami paves the way for exploiting well-defined guest molecule assemblies for biochemistry and nanotechnology applications. PMID- 26149414 TI - Do the effects of prenatal exposure and acute treatment of methamphetamine on anxiety vary depending on the animal model used? AB - The aim of the present study was an evaluation of prenatal exposure to acute methamphetamine (MA) treatment on manifestations of anxiety. Anxiety was evaluated in adult animals in three different experimental models: the Elevated plus-maze (EPM), Social interaction test (SIT) and Ultrasound vocalization (USV). Female rats were administered saline (S) or MA (5 mg/kg) daily throughout their entire gestation period. The male progeny, in adulthood, were administered with challenge dose of S or MA (1 mg/kg) prior to evaluation of anxiety. The study demonstrated that prenatal MA exposure increased the anxiogenic effect on evaluated behaviour patterns in the USV model and to a lesser degree in the EPM model. In addition, the acute MA challenge in adulthood decreased the time spent during social interaction suggesting an anxiogenic effect in the SIT model as well. On the other hand, some of the evaluated parameters (e.g. the number of head-dipping in the EPM and number of dropped boluses in the SIT) also suggest MA induced anxiolytic effects. Sensitization to a MA challenge was apparent in several parameters of the EPM (e.g. increased number of entries to the closed arms, increased stretched attend postures and increased approach-avoid conflicts) and SIT (total social interaction and following). The present data demonstrate that prenatal MA exposure and adult challenge of the same drug have diverse effects on animal behaviour that depends on the type of anxiety model used. PMID- 26149415 TI - Acute stress affects free recall and recognition of pictures differently depending on age and sex. AB - Little is known about age differences in the effects of stress on memory retrieval. Our aim was to perform an in-depth examination of acute psychosocial stress effects on memory retrieval, depending on age and sex. For this purpose, data from 52 older subjects (27 men and 25 women) were reanalyzed along with data from a novel group of 50 young subjects (26 men and 24 women). Participants were exposed to an acute psychosocial stress task (Trier Social Stress Test) or a control task. After the experimental manipulation, the retrieval of positive, negative and neutral pictures learned the previous day was tested. As expected, there was a significant response to the exposure to the stress task, but the older participants had a lower cortisol response to TSST than the younger ones. Stress impaired free recall of emotional (positive and negative) and neutral pictures only in the group of young men. Also in this group, correlation analyses showed a marginally significant association between cortisol and free recall. However, exploratory analyses revealed only a negative relationship between the stress-induced cortisol response and free recall of negative pictures. Moreover, stress impaired recognition memory of positive pictures in all participants, although this effect was not related to the cortisol or alpha-amylase response. These results indicate that both age and sex are critical factors in acute stress effects on specific aspects of long-term memory retrieval of emotional and neutral material. They also point out that more research is needed to better understand their specific role. PMID- 26149416 TI - Hybrid core/shell microparticles and their use for understanding biological processes. AB - Hybrid micro and nanoparticles have become a topic of intense research in recent years. This is due to the special properties of these materials that open new avenues in advanced applications. Herein, we report a novel method for the generation of hybrid particles utilising plasma polymerization. Poly (methyl methacrylate) (PMMA) beads were first coated with a thin allylamine based plasma polymer layer. Gold nanoparticles of engineered size and surface structure were then attached in a controlled manner to the plasma polymer coated beads. To generate uniform chemistry on the outermost surface and to preserve the nanotopography, we deposited a 5-10 nm thin layer of Acpp. We demonstrated that these particles can be utilized in in vivo models to interrogate important biological phenomena. Specifically, we used them in mice to study the inflammatory and foreign body responses to surface nanotopography. The data strongly indicates that surface nanotopography and chemistry can modulate collagen production and the number of adhering immune cells. The method for generating hybrid particles reported here is solvent free and can open new opportunities in fields such as tissue engineering, drug delivery, biosensors, and regenerative medicine. PMID- 26149417 TI - Fabrication of alpha-Fe2O3/In2O3 composite hollow microspheres: A novel hybrid photocatalyst for toluene degradation under visible light. AB - The alpha-Fe2O3/In2O3 composite hollow microspheres were first synthesized through a well-designed two-step hydrothermal approach with an aim to promote the photocatalytic activity of the pure In2O3. The morphologies, phase structures, and optical properties of the resultant samples were systematically characterized by field-emission scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance, and photoluminescence spectroscopy. The alpha-Fe2O3 nanoparticles acted as visible-light sensitizer, which were well-decorated on the surface of the In2O3 hollow microspheres. Meanwhile, the investigation of photocatalytic performance confirmed that the visible-light induced photocatalytic degradation rate of gaseous toluene was improved after the introduction of alpha-Fe2O3 component, which was about 1.6 times higher than that of pure In2O3 sample under identical conditions. Furthermore, some intermediates formed during the photocatalytic oxidation process were also indentified by in situ FTIR spectroscopy. The enhanced photocatalytic performance of the alpha-Fe2O3/In2O3 composites mainly stemmed from the strong visible-light-harvesting ability and the efficient spatial separation of photo-generated electron-hole pairs. PMID- 26149418 TI - Trace element fingerprinting of cockle (Cerastoderma edule) shells can reveal harvesting location in adjacent areas. AB - Determining seafood geographic origin is critical for controlling its quality and safeguarding the interest of consumers. Here, we use trace element fingerprinting (TEF) of bivalve shells to discriminate the geographic origin of specimens. Barium (Ba), manganese (Mn), magnesium (Mg), strontium (Sr) and lead (Pb) were quantified in cockle shells (Cerastoderma edule) captured with two fishing methods (by hand and by hand-raking) and from five adjacent fishing locations within an estuarine system (Ria de Aveiro, Portugal). Results suggest no differences in TEF of cockle shells captured by hand or by hand-raking, thus confirming that metal rakes do not act as a potential source of metal contamination that could somehow bias TEF results. In contrast, significant differences were recorded among locations for all trace elements analysed. A Canonical Analysis of Principal Coordinates (CAP) revealed that 92% of the samples could be successfully classified according to their fishing location using TEF. We show that TEF can be an accurate, fast and reliable method to determine the geographic origin of bivalves, even among locations separated less than 1 km apart within the same estuarine system. Nonetheless, follow up studies are needed to determine if TEF can reliably discriminate between bivalves originating from different ecosystems. PMID- 26149419 TI - Development and Characterization of a Biocompatible Soybean Oil-Based Microemulsion for the Delivery of Poorly Water-Soluble Drugs. AB - The aim of this work was the development and characterization of a biocompatible microemulsion (ME) containing soybean oil (O), phosphatidylcholine/sodium oleate/Eumulgin(r)HRE40 as the surfactant mixture (S) and water or buffer solution as the aqueous phase (W), for oral delivery of the poorly water-soluble drugs sulfamerazine (SMR) and indomethacin (INM). A wide range of combinations to obtain clear oil-in-water (o/w) ME was observed from pseudo-ternary phase diagrams, which was greater after the incorporation of both drugs, suggesting that they acted as stabilizers. Drug partition studies indicated a lower affinity of the drugs for the oil domain when they were ionized and with increased temperature, explained by the fact that both drugs were introduced inside the oil domain, determined by nuclear magnetic resonance. High concentrations of SMR and INM were able to be incorporated (22.0 and 62.3 mg/mL, respectively). The ME obtained presented an average droplet size of 100 nm and a negative surface charge. A significant increase in the release of SMR was observed with the ME with the highest percentage of O, because of the solubilizing properties of the ME. Also, a small retention effect was observed for INM, which may be explained by the differences in the partitioning properties of the drugs. PMID- 26149420 TI - Margaret McCartney: The zombie statistic behind the push for seven day working. PMID- 26149421 TI - Divergence patterns of genic copy number variation in natural populations of the house mouse (Mus musculus domesticus) reveal three conserved genes with major population-specific expansions. AB - Copy number variation represents a major source of genetic divergence, yet the evolutionary dynamics of genic copy number variation in natural populations during differentiation and adaptation remain unclear. We applied a read depth approach to genome resequencing data to detect copy number variants (CNVs) >=1 kb in wild-caught mice belonging to four populations of Mus musculus domesticus. We complemented the bioinformatics analyses with experimental validation using droplet digital PCR. The specific focus of our analysis is CNVs that include complete genes, as these CNVs could be expected to contribute most directly to evolutionary divergence. In total, 1863 transcription units appear to be completely encompassed within CNVs in at least one individual when compared to the reference assembly. Further, 179 of these CNVs show population-specific copy number differences, and 325 are subject to complete deletion in multiple individuals. Among the most copy-number variable genes are three highly conserved genes that encode the splicing factor CWC22, the spindle protein SFI1, and the Holliday junction recognition protein HJURP. These genes exhibit population specific expansion patterns that suggest involvement in local adaptations. We found that genes that overlap with large segmental duplications are generally more copy-number variable. These genes encode proteins that are relevant for environmental and behavioral interactions, such as vomeronasal and olfactory receptors, as well as major urinary proteins and several proteins of unknown function. The overall analysis shows that genic CNVs contribute more to population differentiation in mice than in humans and may promote and speed up population divergence. PMID- 26149423 TI - Properties of self-assembled nanostructures: general discussion. PMID- 26149422 TI - A comparison of salvage infusional chemotherapy regimens for recurrent/refractory multiple myeloma. AB - BACKGROUND: Despite the impact of proteasome inhibitors and immunomodulatory agents, infusional chemotherapy regimens continue to be used for patients with multiple myeloma. To the authors' knowledge, contemporary data regarding salvage chemotherapy regimens are sparse, with no direct comparisons. METHODS: The authors performed a single-institution study comparing 3 salvage chemotherapy regimens in 107 patients with recurrent/refractory multiple myeloma: dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in 52 patients; bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide (VTD-PACE) in 22 patients; and cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) in 33 patients. RESULTS: Differences between treatment groups existed, including higher baseline creatinine for patients treated with CVAD (P<.001) and greater prior use of infusional chemotherapy for those receiving VTD-PACE (P<.001). There was no significant difference in response noted among the 3 regimens: 55% overall (P = .18). For the intent-to-transplant population, a similar percentage were successfully bridged to transplant without further therapy (62%; P = .9). There was no difference in survival observed across the 3 regimens, with an overall median progression-free survival of 4.5 months (95% confidence interval, 3.6-5.5 months [P = .8]) and a median overall survival of 8.5 months (95% confidence interval, 6.1-11 months [P = .8]). Furthermore, there was no statistically significant difference noted among clinically relevant adverse events, although there was a suggestion of fewer adverse events with DCEP. Patients treated with the intent to transplant had superior outcomes for response (odds ratio, 3.40; P = .01), progression-free survival (hazard ratio, 0.28; P<.001), and overall survival (hazard ratio, 0.19; P<.001). CONCLUSIONS: The 3 salvage regimens demonstrated similar responses, survival, and adverse events. Given the short response durations observed in the recurrent/refractory disease setting, infusional chemotherapy is best suited for cytoreduction before more definitive therapy is administered. PMID- 26149424 TI - Results of the Pavlik harness when treating Ortolani-positive hips: predictors of failure and arthrographic findings. AB - BACKGROUND: Predictors of failure of the Pavlik harness in reducing and stabilizing an Ortolani-positive hip remain 'unclear'. The purpose of this study is to investigate the success of the Pavlik harness when treating Ortolani positive hips, to look for predictors of failure of the harness and to analyze the arthrographic findings among these failures. MATERIALS AND METHODS: The medical records of 39 consecutive patients with an Ortolani-positive hip treated initially with a Pavlik harness were reviewed. Data regarding birth order, problems during pregnancy, presentation at birth, delivery, family history of DDH, gender, side involved, bilaterality, onset of treatment, problems related to use of the harness, and time until the harness reduced and stabilized the hip or was abandoned because of a failure were recorded. The presence of plagiocephaly, torticollis or foot deformity was also noted. We looked for predictors of failure among these aspects and report the arthrographic findings of the failures. RESULTS: The mean age when the harness was started was 16.7 days. The mean time until success or failure of the harness in reducing and stabilize the hip was 18.5 days. There were 8 (20.5 %) failures. Multigravida (p = 0.026) and foot deformity (p = 0.023) were associated with failure of the harness. On the other hand, problems during pregnancy (p = 1), presentation at birth (p = 0.078), c section (p = 0.394), family history of DDH (p = 1), gender (0.313), torticollis (p = 1), bilaterality (p = 1) and onset of treatment (p = 0.485) were not associated. Arthrographic abnormalities were found in all failures. CONCLUSION: The Pavlik harness failed to reduce and stabilize the hip in 20.5 % of the newborns with an Ortolani-positive hip. Multigravida and foot deformity were statistically associated with failure of the harness. An anatomical obstacle for reduction was found in all hips with a harness failure. A more teratological than mechanical hip dislocation could be the reason for failure of the Pavlik harness. LEVEL OF EVIDENCE: IV, Retrospective case series. PMID- 26149427 TI - Progressive Onset of Extracardiac and Myocardial Symptoms: Right Heart Failure and Cor Pulmonale in a Young Man With Debilitating Polyneuropathy and Monoclonal Gammopathy. PMID- 26149425 TI - (2S,4E)-2-Hydroxy-4-octen-3-one, a Male-Produced Attractant Pheromone of the Cerambycid Beetle Tylonotus bimaculatus. AB - We report the identification of a novel pheromone structure from males of the cerambycid beetle Tylonotus bimaculatus Haldeman (Cerambycinae: Hesperophanini), a species native to eastern North America. Volatiles collected from adult males contained (2S,4E)-2-hydroxyoct-4-en-3-one (71%), (3R,4E)-3-hydroxyoct-4-en-2-one (15%), (E)-4-octen-2,3-dione (13%), and 2,3-octanedione (1.5%). Four independent field bioassays with synthetic compounds confirmed that adults of both sexes were attracted by the racemate of the major component, (E)-2-hydroxyoct-4-en-3-one. No other cerambycid species were attracted in significant numbers. Attraction of both sexes is consistent with the male-produced pheromones of many other species in the subfamily Cerambycinae, but T. bimaculatus is unusual in having a pheromone chemistry that is so far unique among species in that subfamily. PMID- 26149428 TI - ECG Response: July 7, 2015. PMID- 26149429 TI - Coronary Subclavian Steal Syndrome and Acute Anterior Myocardial Infarction: A New Treatment Dilemma in the Era of Primary Percutaneous Coronary Intervention. PMID- 26149430 TI - Multimodality Imaging of Giant Right Coronary Aneurysm and Postsurgical Coronary Artery Inflammation. PMID- 26149431 TI - Letter by Al-Atassi et al Regarding Article, "Cost-Effectiveness of Percutaneous Coronary Intervention With Drug-Eluting Stents Versus Bypass Surgery for Patients With 3-Vessel or Left Main Coronary Artery Disease: Final Results From the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial". PMID- 26149432 TI - Letter by Weiss and Gotsman Regarding Article, "Evolution From Fibrinolytic Therapy to a Fibrinolytic Strategy for Patients With ST-Segment-Elevation Myocardial Infarction". PMID- 26149433 TI - Response to Letter Regarding Article, "Evolution From Fibrinolytic Therapy to a Fibrinolytic Strategy for Patients With ST-Segment-Elevation Myocardial Infarction". PMID- 26149434 TI - Correction. PMID- 26149435 TI - Homocysteine and MTHFR Mutations. PMID- 26149436 TI - Programmable shunts and headphones: Are they safe together? AB - OBJECT: Programmable shunts have a valuable role in the treatment of patients with hydrocephalus, but because a magnet is used to change valve settings, interactions with external magnets may reprogram these shunts. Previous studies have demonstrated the ability of magnetic toys and iPads to erroneously reprogram shunts. Headphones are even more ubiquitous, and they contain an electromagnet for sound projection that sits on the head very close to the shunt valve. This study is the first to look at the magnetic field emissions of headphones and their effect on reprogrammable shunt valves to ascertain whether headphones are safe for patients with these shunts to wear. METHODS: In this in vitro study of the magnetic properties of headphones and their interactions with 3 different programmable shunts, the authors evaluated Apple earbuds, Beats by Dr. Dre, and Bose QuietComfort Acoustic Noise Cancelling headphones. Each headphone was tested for electromagnetic field emissions using a direct current gaussmeter. The following valves were evaluated: Codman Hakim programmable valve, Medtronic Strata II valve, and Aesculap proGAV. Each valve was tested at distances of 0 to 50 mm (in 5-mm increments) from each headphone. The exposure time at each distance was 1 minute, and 3 trials were performed to confirm results at each valve setting and distance. RESULTS: All 3 headphones generated magnetic fields greater than the respective shunt manufacturer's recommended strength of exposure, but these fields did not persist beyond 5 mm. By 2 cm, the fields levels were below 20 G, well below the Medtronic recommendation of 90 G and the Codman recommendation of 80 G. Because the mechanism for the proGAV is different, there is no recommended gauss level. There was no change in gauss-level emissions by the headphones with changes in frequency and amplitude. Both the Strata and Codman-Hakim valves were reprogrammed by direct contact (distance 0 mm) with the Bose headphones. When a rotation component was added, all 3 headphones reprogrammed the Strata and Codman-Hakim valves at 0 mm. At all distances above 0 mm, the headphones did not affect the shunts. The proGAV valve was not affected by headphones at any distance. CONCLUSIONS: Although all the headphones studied generated significant gauss fields at distances less than 5 mm, the programmable valve settings only changed at a distance of 0 mm (i.e., with direct contact). Given the subcutaneous location of the valve, the authors conclude that is highly unlikely that commercially available or customary headphones can contribute to the reprogramming of shunts. PMID- 26149437 TI - Work-Related Intimate Partner Violence, Acculturation, and Socioeconomic Status Among Employed Mexican Men Enrolled in Batterer Intervention Programs. AB - Intimate partner violence (IPV) has been shown to have considerable effects on women's employment and health. The purpose of this study was to examine work related IPV, acculturation, and socioeconomic status (SES) among Latinos enrolled in batterer intervention programs. Findings indicate that 55% of men interfered with their partner's ability to get to their work, to do their work, and to maintain their job. Positive relationships between acculturation and work-related IPV were observed, and some support was found for a moderating role of SES. Implications for employers and for the conceptualization of violence against women in an employment context are discussed. PMID- 26149438 TI - Violence Against Women in Hong Kong: Results of the International Violence Against Women Survey. AB - In Hong Kong, nearly 1,300 women participated by telephone in the International Violence Against Women Survey in 2006. One in five respondents had experienced violence since age 16. Sexual violence (13.4%) was more frequent than physical violence (11.7%). Women were more likely to be abused by men they knew (13.5%) than by strangers (8%). Compared with other surveyed countries, Hong Kong recorded among the lowest rates of violence by both intimate partners and non partners. These results suggest that cultural influences linked to the interaction of modernization and some protective factors found in the adherence to traditional Chinese values are relevant. PMID- 26149439 TI - Impact of dental health on children's oral health-related quality of life: a cross-sectional study. AB - BACKGROUND: To assess the impact of children's dental health status (DHS) on their oral health-related quality of life (OHRQoL). METHODS: Participants were 11 and 12-year-old children attending public schools in the Kuwait Capital Region. Children's DHS was evaluated by clinical examinations and presented using decayed, missed, filled teeth/surface (DMFT/dmft, DMFS/dmfs); restorative (RI), plaque (PI); and pulp, ulcers, fistula, abscess (PUFA) indices. Children's OHRQoL was assessed using Child's Perception Questionnaire 11-14 (CPQ11-14). Means (SD) and frequencies were used for data description. Different factors were analyzed as predictors of OHRQoL by logistic regression analysis. RESULTS: A total of 440 children aged 11-12 years (50.7 % females) participated in this cross-sectional study. Mean (SD) DMFT/dmft, RI, PI, and PUFA scores were 2.91(2.75), 0.21 (0.34), 3.59 (1.63), 0.31 (0.85), respectively. The mean total CPQ11-14 was 20.72 (16.81). Mean scores of oral-symptoms, functional-limitations, emotional and social well-being were 4.26 (3.32), 5.40 (4.92), 5.48 (6.15), and 5.33 (6.05), respectively. Children with more than four fillings were 95 % less likely to have had oral symptoms than those with no fillings. Children with a DMFT/dmft of 2-3 were 2.8 times more likely to have functional limitation than those with a DMFT/dmft of 0, while children with a DMFT/dmft of more than 4 were 4.4 times more likely to experience limitations. Having two or three non-cavitated lesions reduced the odds of having functional-limitation by 58 %. Children with more than four missing teeth were 45 % more likely to experience emotional stress. Having more than four fissure sealants reduced the odds of having emotional stress by 46 %. CONCLUSIONS: The increase in the number of carious teeth was associated with a limitation in oral functions. Preventive treatment had a positive impact on children's emotional well-being and restorative treatments improved their oral function. PMID- 26149440 TI - Orekhov's Method: Reassessment of In vitro Lipid Uptake Assays. AB - The large research series has become known to the international scientific community 1986 after a publication in The Lancet (2:595). In short, cultures of smooth muscle cells from the human aortic intima or blood-derived monocytes/macrophages were used for measurements of ability of drugs and plant substances to induce or prevent cholesterol deposition in the cells, cultured with the sera from atherosclerosis patients, which was interpreted as pro- or anti-atherogenic effects. However, as discussed previously, the relationship between the uptake of lipids by cultured cells and atherogenesis in vivo must be inverse rather than direct. The up-regulation of lipoprotein receptors is one of the action mechanisms of some cholesterol-lowering drugs. Accordingly, if a drug lowers the uptake of lipids by cultured smooth muscle cells or macrophages, it should be expected to elevate the blood cholesterol level in vivo. Nevertheless, following their concept of blood atherogenicity, the same researchers started to apply apheresis (extracorporeal perfusion of patients' blood for 2 hours through a column with immobilized LDL) aimed at a removal of non-lipid atherogenicity factors. In conclusion, validity of the cell culture method of serum atherogenicity measurement, and testing of pro- or antiatherogenic effects of drugs and dietary supplements is questionable. It would be useful to reproduce some of the cell culture experiments discussed in this letter in an independent laboratory. Verification is necessary prior to preclinical studies in animals and then humans of reportedly anti-atherogenic substances, detected by the cell culture method. PMID- 26149441 TI - Adding smartphone-based cognitive-behavior therapy to pharmacotherapy for major depression (FLATT project): study protocol for a randomized controlled trial. AB - BACKGROUND: Major depression is one of the most debilitating diseases in terms of quality of life. Less than half of patients suffering from depression can achieve remission after adequate antidepressant treatment. Another promising treatment option is cognitive-behavior therapy (CBT). However, the need for experienced therapists and substantive dedicated time prevent CBT from being widely disseminated. In the present study, we aim to examine the effectiveness of switching antidepressants and starting a smartphone-based CBT program at the same time, in comparison to switching antidepressants only, among patients still suffering from depression after adequate antidepressant treatment. METHODS/DESIGN: A multi-center randomized trial is currently being conducted since September 2014. The smartphone-based CBT program, named the "Kokoro-App," for major depression has been developed and its feasibility has been confirmed in a previous open study. The program consists of an introduction, 6 sessions and an epilogue, and is expected to be completed within 9 weeks by patients. In the present trial, 164 patients with DSM-5 major depressive disorder and still suffering from depressive symptoms after adequate antidepressant treatment for more than 4 weeks will be allocated to the Kokoro-App plus switching antidepressant group or the switching antidepressant alone group. The participants allocated to the latter group will receive full components of the Kokoro-App after 9 weeks. The primary outcome is the change in the total score on the Patient Health Questionnaire through the 9 weeks of the program, as assessed at week 0, 1, 5 and 9 via telephone by blinded raters. The secondary outcomes include the change in the total score of the Beck Depression Inventory-II, change in side effects as assessed by the Frequency, Intensity and Burden of Side Effects Rating, and treatment satisfaction. DISCUSSION: An effective and reachable intervention may not only lead to healthier mental status among depressed patients, but also to reduced social burden from this illness. This paper outlines the background and methods of a trial that evaluates the possible additive value of a smartphone-based CBT program for treatment-resistant depression. TRIAL REGISTRATION: UMIN-CTR: UMIN000013693 (registered on 1 June 2014). PMID- 26149442 TI - Quantification of HER2 by Targeted Mass Spectrometry in Formalin-Fixed Paraffin Embedded (FFPE) Breast Cancer Tissues. AB - The ability to accurately quantify proteins in formalin-fixed paraffin-embedded tissues using targeted mass spectrometry opens exciting perspectives for biomarker discovery. We have developed and evaluated a selectedreaction monitoring assay for the human receptor tyrosine-protein kinase erbB-2 (HER2) in formalin-fixed paraffin-embedded breast tumors. Peptide candidates were identified using an untargeted mass spectrometry approach in relevant cell lines. A multiplexed assay was developed for the six best candidate peptides and evaluated for linearity, precision and lower limit of quantification. Results showed a linear response over a calibration range of 0.012 to 100 fmol on column (R(2): 0.99-1.00).The lower limit of quantification was 0.155 fmol on column for all peptides evaluated. The six HER2 peptides were quantified by selected reaction monitoring in a cohort of 40 archival formalin-fixed paraffin-embedded tumor tissues from women with invasive breast carcinomas, which showed different levels of HER2 gene amplification as assessed by standard methods used in clinical pathology. The amounts of the six HER2 peptides were highly and significantly correlated with each other, indicating that peptide levels can be used as surrogates of protein amounts in formalin-fixed paraffin-embedded tissues. After normalization for sample size, selected reaction monitoring peptide measurements were able to correctly predict 90% of cases based on HER2 amplification as defined by the American Society of Clinical Oncology and College of American Pathologists. In conclusion, the developed assay showed good analytical performance and a high agreement with immunohistochemistry and fluorescence in situ hybridization data. This study demonstrated that selected reaction monitoring allows to accurately quantify protein expression in formalin fixed paraffin-embedded tissues and represents therefore a powerful approach for biomarker discovery studies. The untargeted mass spectrometry data is available via ProteomeXchange whereas the quantification data by selected reaction monitoring is available on the Panorama Public website. PMID- 26149444 TI - A cluster randomized clinical trial of a stepped care intervention for depression in primary care (STEPCARE)--study protocol. AB - BACKGROUND: Depression constitutes a significant public health burden and is associated is with high level of individual suffering. Insufficient human and material resources impede the provision of adequate care for persons with the condition in low- and middle-income countries. It is commonly recognized that, to bridge this treatment gap, it is essential to integrate the treatment of depression into primary health care system. METHODS/DESIGN: STEPCARE is a two-arm parallel cluster randomized controlled trial to compare a stepped-care intervention package for depression in primary health care with care as usual in Nigeria. Randomization was conducted at the level of the participating primary health care clinics, while interventions are delivered to consenting individual participants who screen positive on the 9-item patient health questionnaire (PHQ 9 score >= 11) and fulfil the DSM-IV criteria for major depression. Intervention delivered by trained primary health care workers (PHCW) supported by general physicians and psychiatrists as needed is in 3 steps determined by response to treatment. Each step consists of psychological interventions (including psychoeducation, activity scheduling, social network reactivation and problem solving treatment) offered to all participants and, depending on severity and response, medication. Primary outcome, assessed at 12 months following recruitment into the trial, is recovery from depression as shown by a PHQ-9 score of less than 6. Secondary outcomes include changes in disability, quality of life and service utilization assessed at 6 and 12 months. DISCUSSION: The stepped care model examines the effectiveness of an intervention package for depression in which the intensity of treatment is determined by the clinical need of the patients. This approach is designed to make the most efficient use of available resources. TRIAL REGISTRATION: ISRCTN46754188 (ISRTCN registry at isrtcn.com; registered 23 September 2013). PMID- 26149443 TI - Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis. AB - Despite its efficacy, the use of morphine for the treatment of chronic pain remains limited because of the rapid development of tolerance, dependence and ultimately addiction. These undesired effects are thought to be because of alterations in synaptic transmission and neuroplasticity within the reward circuitry including the striatum. In this study we used subcellular fractionation and quantitative proteomics combined with computational approaches to investigate the morphine-induced protein profile changes at the striatal postsynaptic density. Over 2,600 proteins were identified by mass spectrometry analysis of subcellular fractions enriched in postsynaptic density associated proteins from saline or morphine-treated striata. Among these, the levels of 34 proteins were differentially altered in response to morphine. These include proteins involved in G-protein coupled receptor signaling, regulation of transcription and translation, chaperones, and protein degradation pathways. The altered expression levels of several of these proteins was validated by Western blotting analysis. Using Genes2Fans software suite we connected the differentially expressed proteins with proteins identified within the known background protein-protein interaction network. This led to the generation of a network consisting of 116 proteins with 40 significant intermediates. To validate this, we confirmed the presence of three proteins predicted to be significant intermediates: caspase-3, receptor-interacting serine/threonine protein kinase 3 and NEDD4 (an E3-ubiquitin ligase identified as a neural precursor cell expressed developmentally down regulated protein 4). Because this morphine-regulated network predicted alterations in proteasomal degradation, we examined the global ubiquitination state of postsynaptic density proteins and found it to be substantially altered. Together, these findings suggest a role for protein degradation and for the ubiquitin/proteasomal system in the etiology of opiate dependence and addiction. PMID- 26149445 TI - Does physician experience influence the interpretability of focused echocardiography images performed by a pocket device? AB - INTRODUCTION: The use of focused cardiac ultrasound (FoCUS) in a prehospital setting is recommended. Pocket ultrasound devices (PUDs) appear to be well suited to prehospital FoCUS. The main aim of our study was to evaluate the interpretability of echocardiography performed in a prehospital setting using a PUD based on the experience of the emergency physician (EP). METHODS: This was a monocentric prospective observational study. We defined experienced emergency physicians (EEPs) and novice emergency physicians (NEPs) as echocardiographers if they had performed 50 echocardiographies since their initial university training (theoretical training and at least 25 echocardiographies performed with a mentor). Each patient undergoing prehospital echocardiography with a PUD was included. Four diagnostic items based on FoCUS were analyzed: pericardial effusions (PE), right ventricular dilation (RVD), qualitative left ventricular function assessment (LVEF), and inferior vena cava compliance (IVCC). Two independent experts blindly evaluated the interpretability of each item by examining recorded video loops. If their opinions were divided, then a third expert concluded. RESULTS: Fourteen EPs participated: eight (57 %) EEPs and six (43 %) NEPs. Eighty-five patients were included: 34 (40 %) had an echocardiography by an NEP and 51 (60 %) by an EEP. The mean number of interpretable items by echocardiography was three [1; 4]; one [0; 2.25] in the NEP group, four [3; 4] in EEP (p < .01). The patient position was also associated with interpretable items: supine three [2; 4], "45 degrees " three [1; 4], sitting two [1; 4] (p = .02). In multivariate analysis, only EP experience was associated with the number of interpretable items (p = .02). Interpretability by NEPs and EEPs was: 56 % vs. 96 % for LVF, 29 % vs. 98 % for PE, 26 % vs. 92 % for RVD, and 21 % vs. 67 % for IVCC (p < .01 for all). CONCLUSION: FoCUS with PUD in prehospital conditions was possible for EEPs, It is difficult and the diagnostic yield is poor for NEPs. PMID- 26149446 TI - Identification of Obesity and Cardiovascular Risk in Ethnically and Racially Diverse Populations: A Scientific Statement From the American Heart Association. PMID- 26149447 TI - The impact of physician-nurse task shifting in primary care on the course of disease: a systematic review. AB - BACKGROUND: Physician-nurse task shifting in primary care appeals greatly to health policymakers. It promises to address workforce shortages and demands of high-quality, affordable care in the healthcare systems of many countries. This systematic review was conducted to assess the evidence about physician-nurse task shifting in primary care in relation to the course of disease and nurses' roles. METHODS: We searched MEDLINE, Embase, The Cochrane Library and CINAHL, up to August 2012, and the reference list of included studies and relevant reviews. All searches were updated in February 2014. We selected and critically appraised published randomized controlled trials (RCTs). RESULTS: Twelve RCTs comprising 22,617 randomized patients conducted mainly in Europe met the inclusion criteria. Nurse-led care was delivered mainly by nurse practitioners following structured protocols and validated instruments in most studies. Twenty-five unique disease specific measures of the course of disease were reported in the 12 RCTs. While most (84 %) study estimates showed no significant differences between nurse-led care and physician-led care, nurses achieved better outcomes in the secondary prevention of heart disease and a greater positive effect in managing dyspepsia and at lowering cardiovascular risk in diabetic patients. The studies were generally small, of varying follow-up episodes and were at risk of biases. Descriptive details about roles, qualifications or interventions were also incomplete or not reported. CONCLUSION: Trained nurses may have the ability to achieve outcome results that are at least similar to physicians' for managing the course of disease, when following structured protocols and validated instruments. The evidence, however, is limited by a small number of studies reporting a broad range of disease-specific outcomes; low reporting standards of interventions, roles and clinicians' characteristics, skills and qualifications; and the quality of studies. More rigorous studies using validated tools could clarify these findings. PMID- 26149448 TI - Chinese herbal medicine granules (PTQX) for children with moderate to severe atopic eczema: study protocol for a randomised controlled trial. AB - BACKGROUND: Atopic eczema or atopic dermatitis is a chronic inflammatory skin disease. Current conventional medical treatment for moderate and severe atopic eczema is not satisfactory. There is promising evidence derived from randomised clinical trials to support the clinical use of Chinese herbal medicine in the management of atopic eczema. However, the available evidence is compromised by the high risk of bias associated with most of the included trials. Therefore, well-designed and adequately powered randomised clinical trials are needed. The primary aim of this trial is to evaluate the efficacy and safety of oral ingestion of an oral Chinese herbal formula (Pei Tu Qing Xin granules; PTQX) in children aged between 6 and 16 years with moderate to severe atopic eczema. METHODS/DESIGN: We have designed a randomised, double-blind, placebo-controlled, two-arm, parallel clinical trial with 12 weeks of treatment and a 4-week follow up period. A pilot study with 30 participants will be conducted at the RMIT University in Australia to determine the feasibility of the full-scale randomised clinical trial (N = 124). Eczema Area and Severity Index score will be the primary outcome. Secondary outcome measures include change in symptoms using the Patient-Oriented Eczema Measure, the Children's Dermatology Life Quality Index and the use of concomitant medicines. Safety parameters include report of adverse events and pathology tests during the trial period. DISCUSSION: Key elements for conducting a high-quality randomised clinical trial have been addressed in this protocol. Findings from the proposed trial will provide critical evidence regarding Chinese herbal medicine treatment for atopic eczema. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614001172695. Date of Registration: 7 November 2014. PMID- 26149449 TI - Fluctuation of the renal function after discharge from hospital and its effects on drug dosing in elderly patients--study protocol. AB - BACKGROUND: Chronic kidney disease (CKD) is associated with an increased mortality rate, risk of cardiovascular events and morbidity. Impaired renal function is common in elderly patients, and their glomerular filtration rate (GFR) should be taken into account when prescribing renally excreted drugs. In a hospital care setting the GFR may fluctuate substantially, so that the renal function group and therefore the recommended dose, can change within a few days. The magnitude and prevalence of the fluctuation of renal function in daily clinical practice and its potential effects on appropriateness of drug prescriptions after discharge from the hospital is unknown. METHODS/DESIGN: This is a prospective observational study. Patients >= 70 years with renal impairment (eGFR < 60 ml/min/1.73 m(2)) admitted to a geriatric ward are eligible to participate. Participants undergo blood sample collection to measure serum creatinine level at three time points: at discharge from hospital, 14 days, and 2 months after discharge. At these time points the actual medication of the participants is assessed and the number of incorrect prescriptions according to the Dutch guidelines in relation to their estimated renal function is measured. In addition, for a hypothetical selection of drugs, the need for drug dose adaptation in relation to renal function is measured. The outcome of interest is the percentage of patients that changes from renal function group after discharge from hospital compared to the renal function at discharge. In addition, the percentages of patients whose actual medications are incorrectly prescribed and for the hypothetical selection of drugs that would have required dose adaptation will be determined at discharge, 14 days and 2 months after discharge. For each outcome, risk factors which may lead to increased risk for fluctuation of renal function and/or incorrect drug prescribing will also be identified and analysed. DISCUSSION: This study will provide data on changes in renal function in elderly patients after discharge from the hospital with a focus on the medications used. The benefits for healthcare professionals comprise of the creation, adjustment or confirmation of recommendations for the monitoring of the renal function after discharge from hospital of elderly patients. PMID- 26149450 TI - Autonomic nervous system and hypothalamic-pituitary-adrenal axis response to experimentally induced cold pain in adolescent non-suicidal self-injury--study protocol. AB - BACKGROUND: Adolescent non-suicidal self-injury (NSSI) is associated with altered sensitivity to experimentally induced pain. Adolescents engaging in NSSI report greater pain threshold and pain tolerance, as well as lower pain intensity and pain unpleasantness compared to healthy controls. The experience of pain is associated with reactivity of both the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. However, previous research has not yet systematically addressed differences in the physiological response to experimentally induced pain comparing adolescents with NSSI and age- and sex matched healthy controls. METHODS/DESIGN: Adolescents with NSSI and healthy controls undergo repeated painful stimulation with the cold pressor task. ANS activity is continuously recorded throughout the procedure to assess changes in heart rate and heart rate variability. Blood pressure is monitored and saliva is collected prior to and after nociceptive stimulation to assess levels of saliva cortisol. DISCUSSION: The study will provide evidence whether lower pain sensitivity in adolescents with NSSI is associated with blunted physiological and endocrinological responses to experimentally induced pain compared to healthy controls. Extending on the existing evidence on altered pain sensitivity in NSSI, measured by self-reports and behavioural assessments, this is the first study to take a systematic approach in evaluating the physiological response to experimentally induced pain in adolescent NSSI. TRIAL REGISTRATION: Deutsche Register Klinischer Studien, Study ID: DRKS00007807; Trial Registration Date: 13.02.2015. PMID- 26149451 TI - Level walking in adults with and without Developmental Coordination Disorder: An analysis of movement variability. AB - Several studies have shown that Developmental Coordination Disorder (DCD) is a condition that continues beyond childhood. Although adults with DCD report difficulties with dynamic balance, as well as frequent tripping and bumping into objects, there have been no specific studies on walking in this population. Some previous work has focused on walking in children with DCD but variation in the tasks and measures used has led to inconsistent findings. The aim of the current study therefore was to examine the characteristics of level walking in adults with and without DCD. Fifteen adults with DCD and 15 typically developing (TD) controls walked barefoot at a natural pace up and down an 11 m walkway for one minute. Foot placement measures and velocity and acceleration of the body were recorded, as well as measures of movement variability. The adults with DCD showed similar gait patterns to the TD group in terms of step length, step width, double support time and stride time. The DCD group also showed similar velocity and acceleration to the TD group in the medio-lateral, anterior-posterior and vertical direction. However, the DCD group exhibited greater variability in all foot placement and some body movement measures. The finding that adults with DCD have a reduced ability to produce consistent movement patterns is discussed in relation to postural control limitations and compared to variability of walking measures found in elderly populations. PMID- 26149452 TI - Tartrate-Resistant Acid Phosphatase 5b in Young Patients With Sickle Cell Disease and Trait Siblings: Relation to Vasculopathy and Bone Mineral Density. AB - Bone involvement is a frequent cause of acute morbidity in sickle cell disease (SCD). Tartrate-resistant acid phosphatase 5b (TRACP 5b), a bone resorption marker, is produced specifically by activated osteoclasts. We assessed bone mineral density (BMD) in 30 young patients with SCD and 17 asymptomatic patients with sickle cell trait (SCT) compared with 32 healthy controls and determined TRACP 5b levels in relation to vascular complications. Serum ferritin, alkaline phosphatase (ALP), and TRACP 5b were measured. Echocardiography was performed with assessment of BMD using dual energy X-ray absorptiometry (DXA). The BMD was decreased in patients with SCD compared with SCT and controls (P = .005), with no significant difference between the latter 2 groups. Patients with SCD had higher incidence of bone complications than SCT group and controls (P = .03). The SCD group with abnormal DXA scan had higher ferritin and ALP than normal BMD. Serum TRACP 5b was significantly higher in patients with SCD than SCT and controls (P = .003). The TRACP 5b levels were associated with severe vaso-occlusive crisis (P = .022). Patients treated with hydroxyurea and those on chelation therapy had lower TRACP 5b levels than untreated patients. The TRACP 5b level was positively correlated with lactate dehydrogenase, while there was no relation with ferritin, ALP, or BMD. We suggest that bone complications frequently occur in SCD as reflected by low BMD and high ALP and TRACP 5b. Hemolysis and iron overload may be involved in the occurrence of these complications. The lack of correlation between abnormal DXA scan and high TRACP 5b suggests that bone disease in SCD is multifactorial. PMID- 26149453 TI - Ageing effect on flicker-induced diameter changes in retinal microvessels of healthy individuals. AB - PURPOSE: To compare flicker-induced retinal vessel diameter changes in varying age groups with low cardiovascular risk. METHODS: Retinal vascular reactivity to flicker light was assessed by means of dynamic retinal vessel analysis in 57 participants aged 19-30 years, 75 participants aged 31-50 years and 62 participants aged 51-70 years participants. Other assessments included carotid intima-media thickness (c-IMT), augmentation index (AIx), blood pressure profiles, blood lipid metabolism markers and Framingham risk scores (FRS). RESULTS: Retinal arterial dilation amplitude (DA) and postflicker percentage constriction (MC%) were significantly decreased in the oldest group compared to the middle-aged (p = 0.028; p = 0.021) and youngest group (p = 0.003; p = 0.026). The arterial constriction slope (SlopeAC ) was also decreased in the oldest group compared to the youngest group (p = 0.027). On the venous side, MC% was decreased in the middle-aged and oldest groups in comparison with the youngest group (p = 0.015; p = 0.010, respectively). Additionally, men exhibited increased arterial DA (p = 0.007), and percentage dilation (MD%, p < 0.001) in comparison with women, but only in the youngest age group. Both AIx and c-IMT scores increased with age (both p < 0.001); however, no correlations were found between the observed differences in the measured retinal vascular function and systemic parameters. CONCLUSION: In individuals with low cardiovascular risk, there are age-related differences in flicker-induced retinal vessel diameter changes throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the arterial dilatory phase and are only present in young individuals. PMID- 26149454 TI - Physicians using ultrasound in Danish emergency departments are mostly summoned specialists. AB - BACKGROUND: Emergency ultrasound is a relatively new diagnostic discipline. It is used as an extension of the clinical examination and is ideal in the setting of acute illness. The objective of this study was to investigate how many Emergency Departments (EDs) in Denmark have implemented emergency ultrasound. We also wanted to give an idea of how many and which physicians have adopted ultrasound as a diagnostic tool so far. METHODS: The study was a cross-sectional, descriptive, multicenter survey that included all physician staffed EDs in Denmark. An Internet based questionnaire was distributed by e-mail to all heads of department. Those departments who responded that ultrasound was available in their department were included in the second part of the study where all physicians working in the ED were contacted and asked to complete a second questionnaire. RESULTS: All 28 eligible EDs participated in the first part of the study (Response rate: 100 %). 25 EDs (89 %, 95 % CI: 85-93) had ultrasound equipment available. Questionnaires were distributed to 1,872 physicians in these departments and 561 responded (Response rate: 30 %, 95 % CI: 28-32). Overall 257 (46 %, 95 % CI: 42-50) were users of emergency ultrasound and 304 were non-users (54 %, 95 % CI: 50-58). The largest group with 146 respondents (25 %, 95 % CI: 21 29) were anaesthetists with merely consult duty in the ED. When looking exclusively on physicians with on-call duty in the ED, thus excluding anaesthetists, only 146 (35 %, 95 % CI: 30-40) were users of ultrasound while 269 (65 %, 95 % CI: 60-70) were non-users. There was a considerable difference regarding age, level of training, and medical specialty between users and non users. Users were mainly anaesthetists and attending physicians from other departments. The majority of non-users were young physicians with on call duty in the ED. CONCLUSIONS: We have found that although almost all Danish EDs have ultrasound equipment available, few physicians working in the ED seem to have adopted the tool. Emergency Ultrasound is mainly performed by specialists who are summoned to the ED in case of severe acute illness and not by those physicians who comprise the backbone of the ED around the clock. PMID- 26149455 TI - Waterpipe industry products and marketing strategies: analysis of an industry trade exhibition. AB - INTRODUCTION: Understanding product development and marketing strategies of transnational tobacco companies (TTCs) has been of vital importance in developing an effective tobacco control policy. However, comparatively little is known of the waterpipe tobacco industry, which TTCs have recently entered. This study aimed to gain an understanding of waterpipe tobacco products and marketing strategies by visiting a waterpipe trade exhibition. METHODS: In April 2014, the first author attended an international waterpipe trade exhibition, recording descriptions of products and collecting all available marketing items. We described the purpose and function of all products, and performed a thematic analysis of messages in marketing material. RESULTS: We classified waterpipe products into four categories and noted product variation within categories. Electronic waterpipe products (which mimic electronic cigarettes) rarely appeared on waterpipe tobacco marketing material, but were displayed just as widely. Claims of reduced harm, safety and quality were paramount on marketing materials, regardless of whether they were promoting consumption products (tobacco, tobacco substitutes), electronic waterpipes or accessories. CONCLUSIONS: Waterpipe products are diverse in nature and are marketed as healthy and safe products. Furthermore, the development of electronic waterpipe products appears to be closely connected with the electronic cigarette industry, rather than the waterpipe tobacco manufacturers. Tobacco control policy must evolve to take account of the vast and expanding array of waterpipe products, and potentially also charcoal products developed for waterpipe smokers. We recommend that tobacco substitutes be classified as tobacco products. Continued surveillance of the waterpipe industry is warranted. PMID- 26149456 TI - Copper-mediated cyanation of indoles and electron-rich arenes using DMF as a single surrogate. AB - The copper-mediated cyanation of indoles with DMF as a single surrogate has been realized. This approach could be applied for the cyanation of some electron-rich arenes and aryl aldehydes as well. Aryl aldehydes were demonstrated to be the key intermediates in the cascade process of cyanation of indoles and electron-rich arenes. PMID- 26149457 TI - Why sharing matters for electrophysiological data analysis. AB - We present the case for the sharing of electrophysiological datasets and tools for their analysis. Some of the problems, both sociological and technical, associated with improving the sharing of data and analysis tools are discussed. The work that has been done to try to improve data and code sharing in the electrophysiology area is reviewed. The sharing aspects of the current large projects in brain research are considered. PMID- 26149459 TI - Manipulating the in vivo immune response by targeted gene knockdown. AB - Aptamers, nucleic acids selected for high affinity binding to proteins, can be used to activate or antagonize immune mediators or receptors in a location and cell-type specific manner and to enhance antigen presentation. They can also be linked to other molecules (other aptamers, siRNAs or miRNAs, proteins, toxins) to produce multifunctional compounds for targeted immune modulation in vivo. Aptamer siRNA chimeras (AsiCs) that induce efficient cell-specific knockdown in immune cells in vitro and in vivo can be used as an immunological research tool or potentially as an immunomodulating therapeutic. PMID- 26149458 TI - Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer. AB - The treatment of cancer is becoming more precise, targeting specific oncogenic drivers with targeted molecular therapies. The epidermal growth factor receptor has been found to be over-expressed in a multitude of solid tumours. Immunohistochemistry is widely used in the fields of diagnostic and personalised medicine to localise and visualise disease specific proteins. To date the clinical utility of epidermal growth factor receptor immunohistochemistry in determining monoclonal antibody efficacy has remained somewhat inconclusive. The lack of an agreed reproducible scoring criteria for epidermal growth factor receptor immunohistochemistry has, in various clinical trials yielded conflicting results as to the use of epidermal growth factor receptor immunohistochemistry assay as a companion diagnostic. This has resulted in this test being removed from the licence for the drug panitumumab and not performed in clinical practice for cetuximab. In this review we explore the reasons behind this with a particular emphasis on colorectal cancer, and to suggest a way of resolving the situation through improving the precision of epidermal growth factor receptor immunohistochemistry with quantitative image analysis of digitised images complemented with companion molecular morphological techniques such as in situ hybridisation and section based gene mutation analysis. PMID- 26149461 TI - Women worldwide are subjected to abuse in labour, study finds. PMID- 26149460 TI - TERT Polymorphism rs2736100-C Is Associated with EGFR Mutation-Positive Non-Small Cell Lung Cancer. AB - PURPOSE: EGF receptor (EGFR) mutation-positive (EGFRmut(+)) non-small cell lung cancer (NSCLC) may be a unique orphan disease. Previous studies suggested that the telomerase reverse transcriptase (TERT) gene polymorphism is associated with demographic and clinical features strongly associated with EGFR mutations, for example, adenocarcinoma histology, never-smoking history, and female gender. We aim to test the association between TERT polymorphism and EGFRmut(+) NSCLC. EXPERIMENTAL DESIGN: We conducted a genetic association study in Chinese patients with NSCLC (n = 714) and healthy controls (n = 2,520), between the rs2736100 polymorphism and EGFRmut(+) NSCLC. We further tested the association between the EGFR mutation status and mean leukocyte telomere length (LTL). The potential function of rs2736100 in lung epithelial cells was also explored. RESULTS: The rs2736100-C allele was significantly associated with EGFRmut(+) NSCLC [OR, 1.52; 95% confidence interval (CI), 1.28-1.80; P = 1.6 * 10(-6)] but not EGFRmut(-) NSCLC (OR = 1.07, 95% CI, 0.92-1.24, P = 0.4). While patients with NSCLC as a whole have significantly longer LTL than healthy controls (P <= 10(-13)), the EGFRmut(+) patients have even longer LTL than EGFRmut(-) patients (P = 0.008). Meanwhile, rs2736100 was significantly associated with TERT mRNA expression in both normal and tumor lung tissues. All results remained significant after controlling for age, gender, smoking status, and histology (P < 0.05 for all tests). Moreover, the rs2736100 DNA sequence has an allele-specific affinity to nuclear proteins extracted from lung epithelial cells, which led to an altered enhancer activity of the sequence in vitro. CONCLUSIONS: Our study suggests that telomerase and telomere function may be essential for carcinogenesis of EGFRmut(+) NSCLC. Further investigation for the underlying mechanism is warranted. PMID- 26149462 TI - Sex-related differences in joint-angle-specific functional hamstring-to quadriceps strength ratios. AB - PURPOSE: To examine and compare sex-related differences in the functioning of the hamstrings and quadriceps muscles and the isokinetic hamstrings eccentric-to quadriceps concentric functional ratio (H/Q FUNC). METHODS: Fifty male and 46 female young adults completed this study. Each participant carried out an isokinetic assessment to determine isokinetic concentric and eccentric torques during knee extension and flexion actions at 3 different angular velocities (60, 180 and 300 degrees /s) adopting a lying position. The H/Q FUNC was calculated using peak torque (PT) values and 3 different joint-angle-specific torque values (15 degrees , 30 degrees and 45 degrees of knee extension). A repeated measures analysis of variance was used to compare the results, and post hoc analyses using Friedman correction were employed. RESULTS: There were statistically significant effects of angular velocity, joint angle and sex on the H/Q FUNC (p < 0.01). Thus, the H/Q FUNC ratio in both males and females decreases closer to full knee extension and with increasing movement velocity. The H/Q FUNC was also significantly lower in females compared to males, irrespective of moment velocity and joint angle. CONCLUSIONS: The findings of the current study reinforce the need to examine the H/Q FUNC ratio closer to full knee extension (where knee injury is most likely to occur) rather than using PT values which may not be as informative, as well as to focus preventive and rehabilitation training programmes on reducing quadriceps dominance by enhancing eccentric hamstring strength (especially in females who are at higher risk of injury). LEVEL OF EVIDENCE: III. PMID- 26149463 TI - Misfolding caused by the pathogenic mutation G47R on the minor allele of alanine:glyoxylate aminotransferase and chaperoning activity of pyridoxine. AB - Liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5' phosphate (PLP) enzyme, exists as two polymorphic forms, the major (AGT-Ma) and the minor (AGT-Mi) haplotype. Deficit of AGT causes Primary Hyperoxaluria Type 1 (PH1), an autosomal recessive rare disease. Although ~one-third of the 79 disease causing missense mutations segregates on AGT-Mi, only few of them are well characterized. Here for the first time the molecular and cellular defects of G47R Mi are reported. When expressed in Escherichia coli, the recombinant purified G47R-Mi variant exhibits only a 2.5-fold reduction of its kcat, and its apo form displays a remarkably decreased PLP binding affinity, increased dimer-monomer equilibrium dissociation constant value, susceptibility to thermal denaturation and to N-terminal region proteolytic cleavage, and aggregation propensity. When stably expressed in a mammalian cell line, we found ~95% of the intact form of the variant in the insoluble fraction, and proteolyzed (within the N-terminal region) and aggregated forms both in the soluble and insoluble fractions. Moreover, the intact and nicked forms have a peroxisomal and a mitochondrial localization, respectively. Unlike what already seen for G41R-Mi, exposure of G47R-Mi expressing cells to pyridoxine (PN) remarkably increases the expression level and the specific activity in a dose-dependent manner, reroutes all the protein to peroxisomes, and rescues its functionality. Although the mechanism of the different effect of PN on the variants G47R-Mi and G41R-Mi remains elusive, the chaperoning activity of PN may be of value in the therapy of patients bearing the G47R mutation. PMID- 26149464 TI - Biotunable acoustic node assembly of organoids. AB - Bioengineering of 3D microtissues from cell spheroids is demonstrated by employing the vibration of acoustic standing waves and its hydrodynamic effect at the bottom of a liquid-carrier chamber. A large number of cell spheroids (>10(4) ) are assembled in seconds into a closely packed structure in a scaffold-free fashion under nodal pattern of the standing waves in a fluidic environment. PMID- 26149465 TI - A randomized comparison of once weekly epoetin alfa to extended schedule epoetin or darbepoetin in chemotherapy-associated anemia. AB - Erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients with cancer chemotherapy-associated anemia (CAA). Extended-interval ESA dosing (administration less than once weekly) is common with DA, but previous studies suggested that EA might also be administered less often than weekly. In this multicenter prospective trial, 239 CAA patients with Hb <10.5 g/dL were randomized to receive EA 40,000 U subcutaneously once weekly ("40K" arm), EA 80,000 U every 3 weeks ("80K"), EA 120,000 U every 3 weeks ("120K" arm), or DA 500 mcg every 3 weeks ("DA"), for 15 weeks. The primary endpoint was the proportion of patients achieving Hb >= 11.5 g/dL or increment of Hb > 2.0 g/dL from baseline without transfusion. Secondary endpoints included transfusion requirements, adverse events (AEs), and patient-reported outcomes (PROs). There were no significant differences between treatment arms in the proportion of patients achieving Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; P > 0.41 for all comparisons) or requiring RBC transfusion, but the median Hb increment from baseline was higher in the 40K and DA arms compared to the two extended dosing EA arms, and Hb response was achieved soonest in the weekly EA arm. There were no differences in PROs or AEs. The FDA approved schedules tested-weekly EA 40,000 U, and every 3 week DA 500 mcg-are reasonable standards for CAA therapy. PMID- 26149466 TI - Suicide in pediatrics: epidemiology, risk factors, warning signs and the role of the pediatrician in detecting them. AB - Epidemiological data suggests suicide is uncommon in childhood but becomes an extremely serious issue among adolescents.Several risk factors have been identified and include the presence of psychiatric illness, a previous suicide attempt, family factors, substance abuse, sexual and physical abuse, disorders in gender identity or bullying. Pediatricians have a primary role in searching for these risk factors, recognizing them and acting synergistically with other specialists to prevent and treat suicidal behavior.Pediatricians should also be able to identify the "warning signs" for suicide since their presence implies a need for immediate action, as attempted suicide may occur in a few hours or days.The use of antidepressant drugs and its association with suicidal risk in pediatric age is another topic of ongoing debate. Food and Drug Administration has recently introduced the so-called "black box" on antidepressants' packages with the aim of gaining attention to the possible risk of suicide among adolescents who are treated with antidepressants, with a warning that the risk of suicide is higher when starting a therapy or while adjusting its dosage. PMID- 26149468 TI - Left main non culprit ruptured plaque: to treat or no to treat? PMID- 26149467 TI - Quantitative constraint-based computational model of tumor-to-stroma coupling via lactate shuttle. AB - Cancer cells utilize large amounts of ATP to sustain growth, relying primarily on non-oxidative, fermentative pathways for its production. In many types of cancers this leads, even in the presence of oxygen, to the secretion of carbon equivalents (usually in the form of lactate) in the cell's surroundings, a feature known as the Warburg effect. While the molecular basis of this phenomenon are still to be elucidated, it is clear that the spilling of energy resources contributes to creating a peculiar microenvironment for tumors, possibly characterized by a degree of toxicity. This suggests that mechanisms for recycling the fermentation products (e.g. a lactate shuttle) may be active, effectively inducing a mutually beneficial metabolic coupling between aberrant and non-aberrant cells. Here we analyze this scenario through a large-scale in silico metabolic model of interacting human cells. By going beyond the cell autonomous description, we show that elementary physico-chemical constraints indeed favor the establishment of such a coupling under very broad conditions. The characterization we obtained by tuning the aberrant cell's demand for ATP, amino-acids and fatty acids and/or the imbalance in nutrient partitioning provides quantitative support to the idea that synergistic multi-cell effects play a central role in cancer sustainment. PMID- 26149469 TI - Could zoledronic acid prevent root resorption in replanted rat molar? AB - BACKGROUND/AIM: In this study, we evaluated whether zoledronate could suppress the progression of external root resorption in rat due to delayed replantation by inhibiting osteoclastic activity. Also, we estimated the optimal dosage of zoledronate in root treatment of the rat model for a maximum effect of zoledronate. MATERIAL AND METHODS: Maxillary first molars in Sprague Dawley rats (N = 84) were extracted, dried for 60 min, and then replanted. The rats were divided into 6 groups (1 mM alendronate, and 1, 5, 10, 20, 40 MUM zoledronate). At 4 and 8 weeks postreplantation, the animals were sacrificed and evaluated by radiographic and histological analysis. RESULTS AND CONCLUSION: There were no significant differences at 4 weeks. However, at 8 weeks, 10, 20, and 40 MUM ZOL showed more increased radiopaque and smaller periapical lesion in radiographic analysis. In histological analysis, all groups showed similar inflammatory root resorption rate at 4 weeks. However, at 8 weeks, 20 and 40 MUM ZOL showed lower rate than those of other groups (P < 0.05). In concerning of replacement resorption, there were no significant differences statistically. In this animal experiment, zoledronate was capable of limiting the occurrence of root resorption in delayed replantation model. In particular, 20 MUM dosage of zoledronate solution showed the most effective dose in long-term follow up and might be suitable for inhibition of root resorption in delayed tooth replantation. PMID- 26149470 TI - Imiquimod-induced psoriasis-like skin inflammation is suppressed by BET bromodomain inhibitor in mice through RORC/IL-17A pathway modulation. AB - Psoriasis is one of the most common skin disorders characterized by erythematous plaques that result from hyperproliferative keratinocytes and infiltration of inflammatory leukocytes into dermis and epidermis. Recent studies suggest that IL 23/IL-17A/IL-22 cytokine axis plays an important role in the pathogenesis of psoriasis. The small molecule bromodomain and extraterminal domain (BET) inhibitors, that disrupt interaction of BET proteins with acetylated histones have recently demonstrated efficacy in various models of inflammation through suppression of several pathways, one of them being synthesis of IL-17A/IL-22 which primarily depends on transcription factor, retinoic acid receptor-related orphan receptor C (RORC). However, the efficacy and mechanistic aspect of a BET inhibitor in mouse model of skin inflammation has not been explored previously. Therefore, this study investigated the role of BET inhibitor, JQ-1 in mouse model of psoriasis-like inflammation. Mice were topically applied imiquimod (IMQ) to develop psoriasis-like inflammation on the shaved back and ear followed by assessment of skin inflammation (myeloperoxidase activity, ear thickness, and histopathology), RORC and its signature cytokines (IL-17A/IL-22). JQ-1 suppressed IMQ-induced skin inflammation as reflected by a decrease in ear thickness/myeloperoxidase activity, and RORC/IL-17A/IL-22 expression. Additionally, a RORalpha/gamma agonist SR1078 was utilized to investigate the role of RORC in BET-mediated skin inflammation. SR1078 reversed the protective effect of JQ-1 on skin inflammation at both histological and molecular levels in the IMQ model. The current study suggests that BET bromodomains are involved in psoriasis-like inflammation through induction of RORC/IL-17A pathway. Therefore, inhibition of BET bromodomains may provide a new therapy against skin inflammation. PMID- 26149472 TI - High-Curie-Temperature Ferromagnetism in (Sc,Fe)F3 Fluorides and its Dependence on Chemical Valence. AB - A magnetic metal-fluoride system is shown for the first time to have a high Curie temperature (~545 K). The magnetism correlates intimately with the Fe(2+)/Fe(3+) ratio. As the ratio increases, the weak magnetism displayed by unordered magnetic moments intensifies, and these magnetic moments align in parallel. Simultaneously, a magneto-volume effect is also shown to increase the lattice volume. PMID- 26149471 TI - Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens. AB - BACKGROUND: Malaria is a major global cause of deaths and a vaccine is urgently needed. RESULTS: We have employed the P. falciparum merozoite antigens MSP2 3D7/FC27 and AMA1, used them in ELISA, and coupled them in different ways using surface plasmon resonance (SPR) and estimated affinity (measured as kd) of monoclonal as well as naturally-acquired polyclonal antibodies in human plasma. There were major differences in kd depending on how the antigens were immobilized and where the His-tag was placed. For AMA1 we could see correlations with invasion inhibition. Using different immobilizations of proteins in SPR, we could see only moderate correlations with levels of antibodies in ELISA, indicating that in ELISA the proteins were not uniformly bound and that antibodies with many specificities exist in natural immunisation. The correlations between ELISA and SPR were enhanced when only parasite positive samples were included, which may indicate that high affinity antibodies are difficult to maintain over long periods of time. We found higher kd values for MSP2 (indicating lower affinity) compared to AMA1, which might be partly explained by MSP2 being an intrinsically disordered protein, while AMA1 is globular. CONCLUSIONS: For future vaccine studies and for understanding immunity, it is important to consider how to present proteins to the immune system to achieve highest antibody affinities. PMID- 26149473 TI - Influences of extreme weather, climate and pesticide use on invertebrates in cereal fields over 42 years. AB - Cereal fields are central to balancing food production and environmental health in the face of climate change. Within them, invertebrates provide key ecosystem services. Using 42 years of monitoring data collected in southern England, we investigated the sensitivity and resilience of invertebrates in cereal fields to extreme weather events and examined the effect of long-term changes in temperature, rainfall and pesticide use on invertebrate abundance. Of the 26 invertebrate groups examined, eleven proved sensitive to extreme weather events. Average abundance increased in hot/dry years and decreased in cold/wet years for Araneae, Cicadellidae, adult Heteroptera, Thysanoptera, Braconidae, Enicmus and Lathridiidae. The average abundance of Delphacidae, Cryptophagidae and Mycetophilidae increased in both hot/dry and cold/wet years relative to other years. The abundance of all 10 groups usually returned to their long-term trend within a year after the extreme event. For five of them, sensitivity to cold/wet events was lowest (translating into higher abundances) at locations with a westerly aspect. Some long-term trends in invertebrate abundance correlated with temperature and rainfall, indicating that climate change may affect them. However, pesticide use was more important in explaining the trends, suggesting that reduced pesticide use would mitigate the effects of climate change. PMID- 26149474 TI - Transcriptome analysis of the biofilm formed by methicillin-susceptible Staphylococcus aureus. AB - Biofilm formation is regarded as one of the major determinants in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) as pathogens of medical device-related infection. However, methicillin-susceptible S. aureus (MSSA) can also form biofilm in vitro and such biofilms are resistant to vancomycin. Hence, researching the possible mechanisms of MSSA biofilm formation is urgent and necessary. Here, we used S. aureus ATCC25923 as the model strain, and studied gene expression profiles in biofilms after the treatment of ursolic acid and resveratrol using RNA-seq technology. The results showed that only ursolic acid could inhibit biofilm formation, which differed from their applied on the multiple clinical drugs resistant MRSA biofilm. RNA-seq data was validated by examining the expression of six genes involved in biofilm formation by qRT-PCR. These data analysis indicated that the mechanism of the MSSA biofilm formation was different from that of the MRSA, due to absence of accessory gene regulator (agr) function. These findings suggest that biofilms of S. aureus with agr dysfunction may be more resistant than those with agr function. Therefore, the infection from clinical MSSA may be recalcitrant once forming biofilm. Further study is necessary to uncover the mechanisms of biofilm formation in other clinical S. aureus. PMID- 26149475 TI - Frequent aerogenous spread with decreased E-cadherin expression of ROS1 rearranged lung cancer predicts poor disease-free survival. AB - OBJECTIVES: ROS1 rearrangement has been found in a subset of lung cancer and ROS1 rearranged tumors are sensitive to ALK kinase inhibitors. This study sought to evaluate the clinicopathological implications and histomorphological characteristics of ROS1-rearranged tumors, especially micropapillary and aerogenous spread growth and to investigate the usefulness of ROS1 immunohistochemistry as a diagnostic test for ROS1 rearrangement. MATERIALS AND METHODS: ROS1 rearrangement characterizations by fluorescence in situ hybridization and ROS1 protein and E-cadherin expression by immunohistochemistry were performed using 754 non-small cell lung cancer surgical specimens. RESULTS: ROS1 rearrangement was identified in 10 samples. Histologically, all 10 ROS1 rearranged tumors harbored an adenocarcinoma component. Significantly, we noted a high association between ROS1 rearrangement with a micropapillary component (p<0.001), aerogenous spread (p=0.002), and E-cadherin loss (p=0.049). Survival analysis showed that ROS1 rearrangement was significantly associated with a higher risk of tumor recurrence (p=0.024). The best criterion to detect ROS1 rearrangement by immunohistochemistry was an H-score of >=100, with a sensitivity and specificity of 90% and 93.5%, respectively. CONCLUSIONS: ROS1-rearranged adenocarcinoma exhibited distinct morphological and clinicopathological features. Decreased membranous E-cadherin expression and aerogenous spread may be associated with worse disease-free survival. ROS1 immunohistochemistry correlated well with ROS1 gene rearrangement. PMID- 26149477 TI - Immediate postpartum ultrasound evaluation for suspected retained placental tissue in patients undergoing manual removal of placenta. AB - OBJECTIVES: Approximately 1% of term deliveries are complicated by retained products of conception. Untreated, this condition may cause bleeding, infection and intrauterine adhesions. This study assessed whether performing routine bedside uterine ultrasound immediately after manual removal of the placenta reduced the occurrence of undiagnosed, retained products of conception and its associated complications. STUDY DESIGN: A retrospective study was conducted using the records of patients who delivered and underwent manual removal of placenta at a single obstetrics center over a 6-year period. The outcomes of patients who were assessed using immediate bedside ultrasound were compared to a similar group who were treated based on clinical evaluation alone. All patients underwent ultrasound examination prior to discharge. Outcome variables included the rate of additional interventions (medical or surgical), abnormal pre-discharge uterine ultrasound findings, postpartum hemorrhage rate, puerperal fever and length of hospital stay. RESULTS: A total of 399 charts were reviewed. Immediate post procedural ultrasound was performed in 235 patients. The remaining 164 women did not undergo immediate post-procedural ultrasound. All patients underwent an ultrasound examination prior to discharge. Among the patients who had an immediate post-procedural ultrasound, 12 (5.1%) received immediate re intervention (2 methergine, 6 curettage and 4 manual uterine revision) vs. no intervention in the second group (p<0.001). No statistically significant difference was found between the group of patients who had immediate post procedural ultrasound and those who did not, in the rates of postpartum hemorrhage (3.1% vs. 0.7%, p=0.13), abnormal ultrasound findings prior to discharge (14.9% vs. 14.8%, p=0.96) or additional late intervention (7.2% vs. 7.9%, p=0.79), respectively. CONCLUSIONS: Our findings suggest that immediate, bedside uterine ultrasound examination after manual removal of placenta might not change patient outcomes. Furthermore, it might increase unnecessary interventions. Further studies are needed to prospectively assess the benefit of routine uterine ultrasound examination after manual removal of placenta. PMID- 26149476 TI - Dovitinib and erlotinib in patients with metastatic non-small cell lung cancer: A drug-drug interaction. AB - INTRODUCTION: Erlotinib is a FDA approved small molecule inhibitor of epidermal growth factor receptor and dovitinib is a novel small molecule inhibitor of fibroblast growth factor and vascular endothelial growth factor receptor. This phase 1 trial was conducted to characterize the safety and determine the maximum tolerated dose of erlotinib plus dovitinib in patients with previously treated metastatic non-small cell lung cancer. METHODS: Escalating dose cohorts of daily erlotinib and dovitinib dosed 5 days on/2 days off, starting after a 2-week lead in of erlotinib alone, were planned. A potential pharmacokinetic interaction was hypothesized as dovitinib induces CYP1A1/1A2. Only cohort 1 (150 mg erlotinib+300 mg dovitinib) and cohort -1 (150 mg erlotinib+200mg dovitinib) enrolled. Plasma concentrations of erlotinib were measured pre- and post-dovitinib exposure. RESULTS: Two of three patients in cohort 1 had a DLT (grade 3 transaminitis and grade 3 syncope). Two of 6 patients in cohort -1 had a DLT (grade 3 pulmonary embolism and grade 3 fatigue); thus, the study was terminated. Erlotinib exposure (average Cmax 2308+/-698 ng/ml and AUC 0-24 41,030+/-15,577 ng*h/ml) approximated previous reports in the six patients with pharmacokinetic analysis. However, erlotinib Cmax and AUC0-24 decreased significantly by 93% (p=0.02) and 97% (p<0.01), respectively, during dovitinib co-administration. CONCLUSIONS: This small study demonstrated considerable toxicity and a significant pharmacokinetic interaction with a marked decrease in erlotinib exposure in the presence of dovitinib, likely mediated through CYP1A1/1A2 induction. Given the toxicity and the pharmacokinetic interaction, further investigation with this drug combination will not be pursued. PMID- 26149478 TI - Estimating cumulative live-birth rates after IVF treatment with Kaplan-Meier and competing risk methods. AB - OBJECTIVE(S): To explore the use of competing risk (CR) as compared to the commonly used Kaplan-Meier (KM) methodology in estimating the cumulative live birth rate (CLBR) after IVF Treatment in a context of high dropout rates and informative censoring. STUDY DESIGN: We compare the KM and CR methodologies for estimating 2-year CLBR in a retrospective cohort of 2779 patients undergoing 5002 embryo transfers over a period of 9 years, from 2000 to 2008, at KKIVF Centre. RESULTS: We observed a total of 1105 LB (39.8%), and a dropout rate of 44.2% (1228 patients). The overall CLBR is lower with CR compared with KM method (39% vs 52%) after up to nine embryo-transfer cycles over a period of two years. The highest CLBR was achieved for ovulation disorders (57% vs 49%, KM vs CR) followed by male factors (54% vs 43%, KM vs CR), with poorer outcomes from patients with decreased ovarian reserve (37% vs 16%, KM vs CR) and endometriosis (36% vs 25%, KM vs CR). As dropouts in our cohort are generally older and more likely to have poorer ovarian reserves, the CR method, which accounted for these dropouts, is likely to give more meaningful estimation of IVF success rates. CONCLUSION(S): The CR method should be considered as a useful alternative in deriving CLBR for IVF treatment where dropout rates are high and when informative censoring is involved. PMID- 26149479 TI - Prescribing patterns of antenatal corticosteroids in women with threatened preterm labor. AB - OBJECTIVE: To assess the impact of cervical length (CL) measurement and fetal fibronectin testing (fFN) on the clinicians' decision to prescribe antenatal corticosteroids (ACS) to women with symptoms of preterm labor. STUDY DESIGN: This is a secondary analysis of a prospective cohort study including women with symptoms of preterm labor and intact membranes between 24 and 34 weeks' gestation. We compared the proportion prescribed and completed ACS courses, preterm delivery within seven days and median intervals from ACS to delivery in four groups: group 1 CL<10 mm, group 2 CL 10-30 mm and positive fFN, group 3 CL 10-30 mm and negative fFN, group 4 CL>30 mm. RESULTS: ACS were prescribed to 63/65 (97%) women in group 1, 176/192 (91%) in group 2, 111/172 women (65%) in group 3 and 55/242 (23%) in group 4. In group 1, 42 (65%) women delivered within seven days, compared to 34 (18%) in group 2, 6 (3%) in group 3 and 3 (1%) in group 4. Median intervals between ACS and delivery were 6 days (IQR 3-61 days), 44 days (IQR 17-69 days), 53 days (IQR 37-77 days) and 66 days (IQR 43-78 days) in group 1, 2, 3 and 4 respectively. CONCLUSION: ACS were prescribed frequently to women with a CL of 10-30 mm and a negative fFN test or a CL>30 mm. There is room for improvement in the prescription of ACS in these low risk women. PMID- 26149480 TI - A comparative study for adsorption of lysozyme from aqueous samples onto Fe3O4 magnetic nanoparticles using different ionic liquids as modifier. AB - In this paper, nanoparticles of Fe3O4 as well as their modified forms with different ionic liquids (IL-Fe3O4) were prepared and used for adsorption of lysozyme. The mean size and the surface morphology of the nanoparticles were characterized by TEM, XRD and FTIR techniques. Adsorption studies of lysozyme were performed under different experimental conditions in batch system on different modified magnetic nanoparticles such as, lysozyme concentration, pH of the solution, and contact time. Experimental results were obtained under the optimum operational conditions of pH 9.0 and a contact time of 10 min when initial protein concentrations of 0.05-2.0 mg mL(-1) were used. The isotherm evaluations revealed that the Langmuir model attained better fits to the equilibrium data than the Freundlich model. The maximum obtained adsorption capacities were 370.4, 400.0 500.0 and 526.3 mg of lysozyme for adsorption onto Fe3O4 and modified magnetic nanoparticles by [C4MIM][Br], [C6MIM][Br] and [C8MIM][Br] per gram of adsorbent, respectively. The Langmuir adsorption constants were 0.004, 0.019, 0.024 and 0.012 L mg(-1) for adsorptions of lysozyme onto Fe3O4 and modified magnetic nanoparticles by [C4MIM][Br], [C6MIM][Br] and [C8MIM][Br], respectively. The adsorption capacity of lysozyme was found to be dependent on its chemical structure, pH of the solution, temperature and type of ionic liquid as modifier. The applicability of two kinetic models including pseudo-first order and pseudo-second order model was estimated. Furthermore, the thermodynamic parameters were calculated. Protein could desorb from IL-Fe3O4 nanoparticles by using NaCl solution at pH 9.5 and was reused. PMID- 26149481 TI - Prehypertension or masked hypertension-which is responsible for target-organ damage? PMID- 26149482 TI - The importance of masked hypertension in adults with prehypertension. PMID- 26149484 TI - Anticoagulation therapy: Preliminary results for the dabigatran-reversal agent idarucizumab. PMID- 26149483 TI - MicroRNAs in platelet function and cardiovascular disease. AB - Cardiovascular disease--a leading cause of morbidity and mortality among adults is strongly influenced by platelet function through acute thrombotic and atherogenic mechanisms. Pathways that regulate platelet activity and lead to coronary occlusion are central to the pathogenesis of acute coronary syndromes. Platelet activation contributes to other thrombotic disorders and cardiovascular diseases, including stroke. Anucleate platelets are now understood to contain transcripts that might relate to other physiological or pathophysiological conditions, be released into the circulation, participate in protein formation, and engage in horizontal RNA transfer to other vascular cells. These platelet transcripts include microRNAs (miRNAs), which are small noncoding RNAs involved in many molecular processes, most notably regulation of gene expression. In platelets, these noncoding RNAs seem to participate in vascular homeostasis, inflammation, and platelet function. In addition, levels of platelet miRNAs in the circulation are associated with the presence or extent of cardiovascular diseases, such as atrial fibrillation and peripheral vascular disease. Accumulating data suggest mechanistic roles for platelet-derived miRNAs in haemostasis, thrombosis, and unstable coronary syndromes. In addition, evidence suggests that platelet-derived miRNAs might have important roles as biomarkers of cardiovascular disease susceptibility, prognosis, or treatment. PMID- 26149485 TI - Carotid baroreflex activation therapy for resistant hypertension. AB - Arterial baroreceptors are mechanosensitive sensory nerve endings in the walls of the carotid sinuses and aortic arch that buffer the increases and decreases in arterial blood pressure. Electrical field stimulation of the carotid sinus, known as carotid baroreflex activation therapy, holds promise as a novel device-based intervention to supplement, but not replace, drug therapy for patients with resistant hypertension. Acute electrical field stimulation of even one carotid sinus can cause a sufficiently large reflex decrease in blood pressure to overcome offsetting reflexes from the contralateral carotid baroreceptors and aortic baroreceptors that are not paced. However, the initial phase III Rheos Pivotal Trial on continuous carotid baroreceptor pacing for resistant hypertension with the first-generation baroreceptor pacemaker yielded equivocal data on efficacy and adverse effects due to facial nerve injury during surgical implantation. A miniaturized second-generation pacing electrode has seemingly overcome the safety issue, and early results with the new device suggest efficacy of unilateral carotid sinus stimulation in heart failure. A phase III trial of this new device for resistant hypertension has been registered. PMID- 26149487 TI - Venous thromboembolism: The Wells rule is not accurate in hospitalized patients. PMID- 26149486 TI - Cardiovascular biomarkers and sex: the case for women. AB - Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women. PMID- 26149488 TI - Heart failure: Alginate-hydrogel in chronic HF. PMID- 26149489 TI - Mortality and complications after hip fracture among elderly patients undergoing hemodialysis. AB - BACKGROUND: Osteoporotic hip fractures cause high mortality and morbidity in elderly adults. Compared to the general population, subjects with end-stage renal disease and hemodialysis often develop mineral bone disorders and have a higher risk for hip fractures. METHODS: We conducted a matched cohort study design and used competing risk analysis to estimate the cumulative incidence of the complication rate. Subjects aged greater than 60 years with hip fracture were selected from Taiwan's National Health Insurance Research Database covering a period from 1997 to 2007, and these subjects were followed up until 2009. We used the Kaplan-Meier method to estimate the overall survival and used the log-rank test and multiple Cox proportional hazards model to explore the risk factors for survival. The cumulative incidence of the first complication was estimated using competing risk analysis. RESULTS: Among hemodialysis subjects, the three-month, one-year, two-year and five-year mortality rates were 17.3 %, 37.2 %, 51.5 %, and 80.5 %, respectively; the one-year and five-year cumulative incidences of the first surgical complication were 14.2 % and 20.6 %, respectively; and the three month cumulative incidence of the first medical complication was 24.1 %. Hemodialysis subjects presented a 2.32 times (95 % CI: 2.16-2.49) higher hazard ratio of overall death, 1.15 times (95 % CI: 1.01-1.30) higher sub-hazard ratio (sub-HR) of surgical complications, and 1.35 times (95 % CI: 1.21-1.52) higher sub-HR of the first medical complication than non-hemodialysis controls. CONCLUSIONS: The overall mortality and complication rates of hemodialysis subjects after surgery for hip fracture were significantly higher than those of non-hemodialysis subjects. Further prospective studies which include important risk factors are necessary to more precisely quantify the adjusted effect of hemodialysis. PMID- 26149490 TI - Reduced cortical thickness in right Heschl's gyrus associated with auditory verbal hallucinations severity in first-episode schizophrenia. AB - BACKGROUND: Auditory verbal hallucinations (AVHs) represent one of the most intriguing phenomena in schizophrenia, however, brain abnormalities underlying AVHs remain unclear. The present study examined the association between cortical thickness and AVHs in first-episode schizophrenia. METHOD: High-resolution MR images were obtained in 49 first-episode schizophrenia (FES) patients and 50 well matched healthy controls (HCs). Among the FES patients, 18 suffered persistent AVHs ("auditory hallucination" AH group), and 31 never experienced AVHs ("no hallucination" NH group). The severity of AVHs was rated by the Auditory Hallucinations Rating Scale (AHRS). Cortical thickness differences among the three groups and their association with AVHs severity were examined. RESULTS: Compared to both HCs and NH patients, AH patients showed lower cortical thickness in the right Heschl's gyrus. The degree of reduction in the cortical thickness was correlated with AVH severity in the AH patients. CONCLUSIONS: Abnormalities of cortical thickness in the Heschl's gyrus may be a physiological factor underlying auditory verbal hallucinations in schizophrenia. PMID- 26149492 TI - [The diseased vitreous body: Malformations, developmental disorders and opacities]. AB - Remnants of a persistent hyaloid artery can occasionally cause cataracts and traction on the retina at the posterior pole of the eye.It is the task of the ophthalmologist to weigh up the risk of amblyopia against the risks of vitrectomy and lensectomy. The retina is primarily intact. This is different from the group of hereditary vitreoretinal dystrophies where defects in the retina and vitreous body contribute equally to the overall clinical manifestations. Familial exudative vitreoretinopathy (FEVR) of childhood is sometimes misdiagnosed as uveitis. Retinal exudates leak from enormously permeable retinal vessels and it is necessary to completely remove such abnormal vessels to stop progression. The peculiar vitreous opacities consist of paper-like veils which are stacked like onion skins. The FEVR simulates retinopathy of prematurity and other exudative vitreoretinopathies. Stickler and Wagner syndromes are associated with a high risk of rhegmatogenous retinal detachment, similar to giant retinal tears. Occasionally, extraocular manifestations, such as hyperextensive joints are indicative of a systemic connective tissue disease.The peripheral retina is mechanically weak and susceptible to tears and giant or multiple tears can occur. The prognosis is further aggravated by an elevated risk of proliferative vitreoretinopathy (PVR). It is, therefore, essential to identify the risk profile in this constellation and bear the risk of PVR in mind when selecting a treatment regimen, similar to that for giant tear retinal detachment. PMID- 26149491 TI - Characterisation of liver pathogenesis, human immune responses and drug testing in a humanised mouse model of HCV infection. AB - OBJECTIVE: HCV infection affects millions of people worldwide, and many patients develop chronic infection leading to liver cancers. For decades, the lack of a small animal model that can recapitulate HCV infection, its immunopathogenesis and disease progression has impeded the development of an effective vaccine and therapeutics. We aim to provide a humanised mouse model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies. DESIGN: Recently, we have established human liver cells with a matched human immune system in NOD-scid Il2rg(-/-) (NSG) mice (HIL mice). These mice are infected with HCV by intravenous injection, and the pathologies are investigated. RESULTS: In this study, we demonstrate that HIL mouse is capable of supporting HCV infection and can present some of the clinical symptoms found in HCV-infected patients including hepatitis, robust virus-specific human immune cell and cytokine responses as well as liver fibrosis and cirrhosis. Similar to results obtained from the analysis of patient samples, the human immune cells, particularly T cells and macrophages, play critical roles during the HCV associated liver disease development in the HIL mice. Furthermore, our model is demonstrated to be able to reproduce the therapeutic effects of human interferon alpha 2a antiviral treatment. CONCLUSIONS: The HIL mouse provides a model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies. It could also serve as a platform for antifibrosis and immune modulatory drug testing. PMID- 26149493 TI - The influence of patient beliefs and treatment satisfaction on the discontinuation of current first-line antiretroviral regimens. AB - OBJECTIVES: Large cohort studies have shown a high rate of first-line combination antiretroviral therapy (cART) regimen discontinuation in HIV-infected patients, attributed to characteristics of the cART regimen or toxicity. METHODS: A cohort study of 274 patients receiving a first-line regimen was carried out. Patients' perceptions and beliefs prior to initiation were assessed using an attitude towards medication scale (0-15 points), and their satisfaction during therapy was assessed using an HIV treatment satisfaction questionnaire (HIVTSQ). Treatment discontinuation was defined as any switch in the cART regimen. RESULTS: During 474.8 person-years of follow-up, 63 (23%) patients changed their cART regimen, mainly because of toxicity/intolerance (42; 67%). The overall rate of change was 13.2 per 100 patient-years [95% confidence interval (CI) 11.1-16.4 per 100 patient-years]. An efavirenz (EFV)-based single tablet regimen showed the highest rate of adverse events (27%), but the lowest rate of change (16%; 7.44 per 100 patient-years). Cox regression revealed a decreased hazard of first regimen termination with better initial attitude towards drugs [hazard ratio (HR) 0.76; 95% CI 0.62-0.93; P < 0.01] and higher satisfaction (HR 0.94; 95% CI 0.89-0.99; P = 0.01), and an increased hazard of termination with the presence of adverse events (HR 7.7; 95% CI 2.4-11.6; P < 0.01). One-third of patients (18 of 59; 31%) with mild/moderate adverse events (which were mainly central nervous system symptoms) continued the regimen; these patients, compared with those discontinuing therapy, showed better perception of therapy (mean score 14.4 versus 12.1, respectively; P = 0.05) and greater satisfaction during therapy (mean score 50.6 versus 44.6, respectively; P = 0.04). CONCLUSIONS: Patients' beliefs and satisfaction with therapy influence the durability of the first antiretroviral regimen. These patient-related factors modulate the impact of mild adverse events, and could explain differences in the rate of discontinuation. PMID- 26149496 TI - B-1 phagocytes: the myeloid face of B-1 cells. AB - The relationship between malignant B cells and macrophages has long been established. Furthermore, evolutionary studies have demonstrated that B cells from early vertebrates have both phagocytic and antibody production capabilities. In addition to their lymphoid nature, B-1 cells retain several myeloid characteristics. Various reports have demonstrated that B-1 cells can differentiate into phagocytes. However, descriptions of B-1 cells as a novel phagocyte cell member are rarely found in the literature. This review aims to present the available data regarding B-1 cell-derived phagocytes and also discusses how their existence might be relevant to hematopoiesis and immune responses. PMID- 26149494 TI - Microglia and astrocytes attenuate the replication of the oncolytic vaccinia virus LIVP 1.1.1 in murine GL261 gliomas by acting as vaccinia virus traps. AB - BACKGROUND: Oncolytic virotherapy is a novel approach for the treatment of glioblastoma multiforme (GBM) which is still a fatal disease. Pathologic features of GBM are characterized by the infiltration with microglia/macrophages and a strong interaction between immune- and glioma cells. The aim of this study was to determine the role of microglia and astrocytes for oncolytic vaccinia virus (VACV) therapy of GBM. METHODS: VACV LIVP 1.1.1 replication in C57BL/6 and Foxn1(nu/nu) mice with and without GL261 gliomas was analyzed. Furthermore, immunohistochemical analysis of microglia and astrocytes was investigated in non , mock-, and LIVP 1.1.1-infected orthotopic GL261 gliomas in C57BL/6 mice. In cell culture studies virus replication and virus-mediated cell death of GL261 glioma cells was examined, as well as in BV-2 microglia and IMA2.1 astrocytes with M1 or M2 phenotypes. Co-culture experiments between BV-2 and GL261 cells and apoptosis/necrosis studies were performed. Organotypic slice cultures with implanted GL261 tumor spheres were used as additional cell culture system. RESULTS: We discovered that orthotopic GL261 gliomas upon intracranial virus delivery did not support replication of LIVP 1.1.1, similar to VACV-infected brains without gliomas. In addition, recruitment of Iba1(+) microglia and GFAP(+) astrocytes to orthotopically implanted GL261 glioma sites occurred already without virus injection. GL261 cells in culture showed high virus replication, while replication in BV-2 and IMA2.1 cells was barely detectable. The reduced viral replication in BV-2 cells might be due to rapid VACV-induced apoptotic cell death. In BV-2 and IMA 2.1 cells with M1 phenotype a further reduction of virus progeny and virus-mediated cell death was detected. Application of BV-2 microglial cells with M1 phenotype onto organotypic slice cultures with implanted GL261 gliomas resulted in reduced infection of BV-2 cells, whereas GL261 cells were well infected. CONCLUSION: Our results indicate that microglia and astrocytes, dependent on their activation state, may preferentially clear viral particles by immediate uptake after delivery. By acting as VACV traps they further reduce efficient virus infection of the tumor cells. These findings demonstrate that glia cells need to be taken into account for successful GBM therapy development. PMID- 26149495 TI - Glutathione Depletion Accelerates Cigarette Smoke-Induced Inflammation and Airspace Enlargement. AB - The study objective was to assess age-related changes in glutathione (GSH) adaptive response to cigarette smoke (CS) exposure. Older cigarette smokers show a decline (67%) in lung epithelial lining fluid (ELF) GSH and a 1.8-fold decreased GSH adaptive response to cigarette smoking with a concomitant elevation (47%) of exhaled nitric oxide compared with younger smokers. In order to isolate the changes in tissue GSH from other age-related effects, pharmacological inhibition of the rate limiting step in GSH synthesis was employed to examine the lung's response to CS exposure in young mice. The gamma-glutamylcysteine ligase inhibitor L-buthionine-sulfoximine (BSO) was administered in the drinking water (20 mM) to decrease by half the in vivo GSH levels to those found in aged mice and humans. Mice were then exposed to CS (3 h/day) for 5 or 15 days. Biochemical analysis of the ELF and lung tissue revealed an inhibition of the CS-induced GSH adaptive response by BSO with a concurrent increase in mixed protein-GSH disulfides indicating increased cysteine oxidation. The prevention of the GSH adaptive response led to an increase in pro-inflammatory cytokines present in the lung. Airspace enlargement is a hallmark of lung emphysema and was observed in mice treated with BSO and exposed to CS for as little as 15 days, whereas these types of changes normally take up to 6 months in this model. BSO treatment potentiated both lung elastase and matrix metalloproteinase activity in the CS group. These data suggest that age-related decline in the GSH adaptive response can markedly accelerate many of the factors thought to drive CS-induced emphysema. PMID- 26149497 TI - Well-Defined Protein/Peptide-Polymer Conjugates by Aqueous Cu-LRP: Synthesis and Controlled Self-Assembly. AB - The synthesis of well-defined protein/peptide-polymer conjugates with interesting self-assembly behavior via single electron transfer living radical polymerization in water is described. A range of protein/peptides with different physical and chemical properties have been modified to macroinitiators and optimized polymerization conditions ensure successful polymerization from soluble, insoluble, and dispersed protein/peptide molecules or protein aggregates. This powerful strategy tolerates a range of functional monomers and mediates efficient homo or block copolymerization to generate hydrophilic polymers with controlled molecular weight (MW) and narrow MW distribution. The polymerizations from bovine insulin macroinitiators follow surface-initiated "grafting from" polymerization mechanism and may involve a series of self-assembly and disassembly processes. Synthesized insulin-polymer conjugates form spheres in water, and the self assembly behavior could be controlled via thermal control, carbohydrate-protein interaction, and protein denaturation. PMID- 26149499 TI - Novel Spectrofluorimetric Method for the Determination of Perindopril Erbumine Based on Charge Transfer Reaction with 7-Hydroxycoumarin. AB - A novel, simple, selective and sensitive spectrofluorimetric method was developed and validated for the determination of perindopril erbumine using 7 hydroxycoumarin. Perindopril erbumine was found to react with 7-hydroxycoumarin in acetonitrile resulting in a new fluorescent product with about 58 nm blue shifted emission. The fluorescence of the complex was measured at 440 nm after excitation at 350 nm in acetonitrile. Under the optimum conditions, the fluorescence intensity was linear over a concentration range of 2.0-16.0 MUg/mL (R(2) = 1) with a detection limit of 0.054 MUg/mL. The proposed method was fully validated and successfully applied to the analysis of perindopril erbumine in pure form and tablets. Statistical comparison of the results obtained by the proposed and reference method revealed no significant differences in the performance of the two methods regarding the accuracy and precision respectively. The method was shown to be highly specific in the presence of indapamide, a diuretic that is commonly combined with perindopril erbumine. A proposal for the reaction pathway with 7-hydroxycoumarin was postulated. PMID- 26149498 TI - Tumour necrosis factor-alpha inhibition can stabilize disease in progressive vitiligo. AB - Tumour necrosis factor (TNF)-alpha, a proinflammatory cytokine central to many autoimmune diseases, has been implicated in the depigmentation process in vitiligo. We review its role in vitiligo by exploring its pro- and anti inflammatory properties and examine the effects of blocking its actions with TNF alpha antagonist therapeutics in reports available in the literature. We found that TNF-alpha inhibition halts disease progression in patients with progressive vitiligo but that, paradoxically, treatment can be associated with de novo vitiligo development in some patients when used for other autoimmune conditions, particularly when using adalimumab and infliximab. These studies reinforce the importance of stating appropriate outcomes measures, as most pilot trials propose to measure repigmentation, whereas halting depigmentation is commonly overlooked as a measure of success. We conclude that TNF-alpha inhibition has proven useful for patients with progressive vitiligo, where TNF-alpha inhibition is able to quash cytotoxic T-cell-mediated melanocyte destruction. However, a lingering concern for initiating de novo disease will likely prevent more widespread application of TNF inhibitors to treat vitiligo. PMID- 26149500 TI - Fluorescence Titrations of Bio-relevant Complexes with DNA: Synthesis, Structural Investigation, DNA Binding/Cleavage, Antimicrobial and Molecular Docking Studies. AB - In the present work, we attempted to develop new metal complexes (Cu(II), Co(II), Ni(II) and Zn(II)) of the imine ligand which was synthesized from 9,10 phenanthrenequinone and para-anisidine. With an intention to make the complexes most stable, very special chelating amino acid has been coordinated to the metal centre. The resultant metal complexes have been characterized by variety of techniques including FT-IR, UV-Vis., (1)H NMR, (13)C NMR, powder XRD, EPR and mass spectral studies. The interaction of the complexes with DNA has been effectively examined and explored by fluorescence titration, UV-Vis absorption, viscometer titration, cyclic voltammetry (CV) and differential pulse voltammetry. Moreover, molecular docking analysis has been performed to understand the nature of binding of the complexes with DNA. These studies prove that CT DNA interaction of the complexes follows intercalation mode. The metal complexes exhibit effective cleavage of pUC19 DNA by an oxidative cleavage mechanism. The antimicrobial screening indicates that these complexes are good antimicrobial agents against various organisms. PMID- 26149501 TI - Phosphorylation of phosphatidylinositol 4-phosphate 5-kinase gamma by Akt regulates its interaction with talin and focal adhesion dynamics. AB - The type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family members and their lipid product, phosphatidylinositol 4,5-bisphosphate (PIP2) are important regulators of actin cytoskeleton. PIP5Kgamma 90kDa (PIP5Kgamma90), an isoform of PIP5K, localizes to focal adhesions (FAs) and is activated via its interaction with the cytoskeletal protein, talin. Currently, regulatory signaling pathways of talin-PIP5Kgamma90 interaction related to FA dynamics and cell motility are not well understood. Considering the presence of Akt consensus motifs in PIP5Kgamma90, we examined a potential link of Akt activation to talin PIP5Kgamma90 interaction. We found that Akt phosphorylated PIP5Kgamma90 specifically at serine 555 (S555) in vitro and in epidermal growth factor (EGF) treated cells phosphoinositide 3-kinase-dependently. EGF treatment suppressed talin-PIP5Kgamma90 interaction and PIP2 levels. Similarly, a phosphomimetic mutant (S555D), but not non-phosphorylatable mutant (S555A), of PIP5Kgamma90 had reduced talin binding affinity, lowered PIP2 levels, and was dislocated from FAs. The S555D mutant also caused decreases in actin stress fibers and vinculin positive FAs. Moreover, assembly and disassembly of FAs were enhanced by S555D expression and EGF-induced cell migration was relatively low in S555A-expressing cells compared to wild-type-expressing cells. PIP5Kgamma87, a PIP5Kgamma splice variant lacking the talin binding motif, was phosphorylated by Akt, which, however, hardly affected PIP2 levels. Taken together, our results suggested that Akt-mediated PIP5Kgamma90 S555 phosphorylation is a novel regulatory point for talin binding to control PIP2 level at the FAs, thereby modulating FA dynamics and cell motility. PMID- 26149502 TI - Stabilization of microtubular cytoskeleton protects neurons from toxicity of N terminal fragment of cytosolic prion protein. AB - Prion protein (PrP) mislocalized in the cytosol has been presumed to be the toxic entity responsible for the neurodegenerative process in transmissible spongiform encephalopathies (TSE), also called prion diseases. The mechanism underlying the neurotoxicity of cytosolic PrP (cytoPrP) remains, however, unresolved. In this study we analyze toxic effects of the cell-penetrating PrP fragment, PrP1-30- encompassing residues responsible for binding and aggregation of tubulin. We have found that intracellularly localized PrP1-30 disassembles microtubular cytoskeleton of primary neurons, which leads to the loss of neurites and, eventually, necrotic cell death. Accordingly, stabilization of microtubules by taxol reduced deleterious effects of cytosolic PrP1-30. Furthermore, we have demonstrated that decreased phosphorylation level of microtubule-associated proteins (MAPs), which also increases stability of microtubular cytoskeleton, protects neurons from the toxic effects of PrP1-30. CHIR98014 and LiCl- inhibitors of glycogen synthase kinase 3 (GSK-3), a major kinase responsible for phosphorylation of MAPs, inhibited PrP1-30-induced disruption of microtubular cytoskeleton and increased viability of peptide-treated neurons. We have also shown that the N-terminal fragment of cytoPrP may cause the loss of dendritic spines. PrP1-30-induced changes at the level of spines have also been prevented by stabilization of microtubules by taxol as well as LiCl. These observations indicate that the neurotoxicity of cytoPrP is tightly linked to the disruption of microtubular cytoskeleton. Importantly, this study implies that lithium, the commonly used mood stabilizer, may be a promising therapeutic agent in TSE, particularly in case of the disease forms associated with accumulation of cytoPrP. PMID- 26149503 TI - [Oxidative stress and atherosclerosis]. AB - Atherosclerosis is a leading cause of death in developed countries. Genetic susceptibility and environmental factors play a role in the pathogenesis. Most of these factors lead to endothelial dysfunction and other pro-atherogenic processes by causing oxidative stress. Atherosclerosis typically develops at the curved and branched regions of the arterial tree, where the laminar blood flow is disturbed. This leads to increased permeability of the endothelium to low density lipoprotein molecules, which accumulate in the intima and are oxidised by vascular cells. Oxidised low density lipoprotein takes part in many phases of atherogenesis: stimulates the binding of monocytes to the endothelium, foam cell formation, the development of plaques, plaque destabilization and thrombotic complications. Since oxidative stress plays an important role in atherogenesis, it has been suggested that antioxidant molecules might have anti-atherogenic function. Many clinical investigations have shown that antioxidants such as N acetylcystein, vitamin E and C, folic acid, and estrogens can prevent atherosclerosis, however, randomized studies failed to confirm this effect. PMID- 26149504 TI - [Revaluation of the concept of developmental abnormality: the importance of faulty perinatal imprinting]. AB - The classic definition of developmental abnormalities referred to malformations observed at birth. Later the functional teratogenicity was also recognized and accepted, which can be revealed in functional abnormalities caused by harms during the intrauterine development and can be manifested at any time of life. However, the ontogeny is not closed with the birth, because some systems or organs are developing for a long time after it, and can be influenced by different factors. From this aspect the perinatal period is especially important when the mutual adjustment of the receptor-hormone system is taking place and the hormonal imprinting develops. If this is faulty, it influences the hormone binding capacity of receptors that has consequences for life. The faulty hormonal imprinting is functionally teratogen; it provokes a fault up to the level of a malformation and aggravated with its heredity to the progenies. False imprinting is provoked (in animal experiments, proportioning to human doses) by drugs acting at receptor level, as oxytocin, steroid hormone analogues (pregnancy protectors, oral contraceptives, surfactants), vitamin A and D, environmental pollutant endocrine disruptors (benzpyrene, bisphenol A, pesticides, herbicides) and certain soybean components, etc. From this aspect these are functional teratogens, and their evasion in prevention as well as therapy seems to be vital. This means that the concept of developmental abnormality must be broadened, as developmental abnormalities: 1.) can originate not only in the intrauterine period, but also perinatally or even later, 2.) it can be manifested at any time of life, 3.) it can be present in a latent form which can be activated by inner or outer environmental factors, 4.) the faulty hormonal imprinting is a teratogen factor. PMID- 26149505 TI - [Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease]. AB - It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction. PMID- 26149506 TI - [Alternative and complementary medicine from the primary care physician's viewpoint]. AB - INTRODUCTION: The patients initiate the use of complementary and alternative medicine and this often remains hidden from their primary care physician. AIM: To explore general practitioners' knowledge and attitude towards complementary and alternative medicine, and study the need and appropriate forms of education, as well as ask their opinion on integration of alternative medicine into mainstream medicine. METHOD: A voluntary anonymous questionnaire was used on two conferences for general practitioners organized by the Family Medicine Department of Semmelweis University. Complementary and alternative medicine was defined by the definition of the Hungarian Academy of Sciences and certified modalities were all listed. RESULTS: 194 general practitioners answered the questionnaire (39.8% response rate). 14% of the responders had licence in at least one of the complementary and alternative therapies, 45% used complementary and alternative therapy in their family in case of illness. It was the opinion of the majority (91.8%) that it was necessary to be familiar with every method used by their patients, however, 82.5% claimed not to have enough knowledge in complementary medicine. Graduate and postgraduate education in the field was thought to be necessary by 86% of the responders; increased odds for commitment in personal education was found among female general practitioners, less than 20 years professional experience and personal experience of alternative medicine. CONCLUSIONS: These data suggest that general practitioners would like to know more about complementary and alternative medicine modalities used by their patients. They consider education of medical professionals necessary and a special group is willing to undergo further education in the field. PMID- 26149507 TI - [Successful surgical management of aortico-left ventricular tunnel using modern noninvasive diagnostic imaging methods]. AB - Aortico-left ventricular tunnel is a rare congenital cardiac defect, which bypasses the aortic valve via the paravalvar connection from the aorta to the left ventricle. The authors present the case of a 14-year-old boy with aortico left ventricular tunnel in whom the aortic orifice arose from the right aortic sinus and was closed by a pericardial patch. The diagnosis was confirmed by combined two-dimensional and real time three-dimensional echocardiogram and magnetic resonance imaging. This is the first case, in which these complex diagnostic imaging methods have been used in the pre- and postoperative management of this defect. Optimally the new transthoratic three-dimensional echocardiography would be needed to define the anatomy and functional consequences of the aortico-left ventricular tunnel and in the postoperative follow-up. PMID- 26149508 TI - [Diagnosis at first glance]. PMID- 26149509 TI - [Memorial celebrations for the 200th anniversary of the birth of Lajos Markusovszky in Csorba (Strba)]. PMID- 26149511 TI - Dynamical bridge between brain and mind. AB - The bridge between brain structures as computational devices and the content of mental processes hinges on the solution of several problems: (i) inference of the cognitive brain networks from neurophysiological and imaging data; (ii) inference of cognitive mind networks - interactions between mental processes such as attention and working memory - based on cognitive and behavioral experiments; and (iii) the discovery of general dynamical principles for cognition based on dynamical models. In this opinion article, we focus on the third problem and discuss how it provides the bridge between the solutions to the first two problems. We consider the possibility of creating low-dimensional dynamical models from multidimensional spatiotemporal data and its application to robust sequential cognitive processes in the context of finite processing capacity of the mind. PMID- 26149510 TI - Long-QT Syndrome and Therapy for Attention Deficit/Hyperactivity Disorder. AB - INTRODUCTION: Stimulants are the mainstay therapy for attention deficit/hyperactivity disorder (ADHD) and are associated with adrenergic side effects. There are limited data on the clinical course of patients treated for ADHD who have long-QT syndrome (LQTS), for which beta-blockade is the goal of therapy. METHODS: LQTS patients from the Rochester-based LQTS Registry (open enrollment between 1979 and 2003; follow-up from 1979 to present) treated with stimulant or nonstimulant ADHD medications (n = 48) were compared to a 2:1 age-, gender-, and QTc-duration matched LQTS control group not exposed to ADHD medications (n = 96). Kaplan-Meier and Cox proportional hazards regression analyses were used to evaluate risk of cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) in LQTS patients treated with ADHD medications. RESULTS: During a mean follow-up of 7.9 +/- 5.4 years after initiation of ADHD medication at a mean age 10.7 +/-7.3 years, there was a 62% cumulative probability of cardiac events in the ADHD treatment group compared to 28% in the matched LQTS control group (P < 0.001). Time-dependent use of ADHD medication was associated with an increased risk for cardiac events (HR = 3.07; P = 0.03) in the multivariate Cox model adjusted for time-dependent beta-blocker use and prior cardiac events. Subgroup gender analyses showed that time-dependent ADHD medication was associated with an increased risk in male LQTS patients (HR = 6.80, P = 0.04). CONCLUSIONS: LQTS patients treated with ADHD medications have increased risk for cardiac events, particularly syncope, and this risk is augmented in males. The findings highlight the importance of heightened surveillance for LQTS patients on ADHD medications. PMID- 26149512 TI - Conventional induction and maintenance treatment of Antineutrophil cytoplasmic antibodies-associated vasculitis - still of value for our patients? AB - INTRODUCTION: Antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) is a group of autoimmune diseases characterized by the necrotizing inflammation of small vessels and associated with the antineutrophil cytoplasmic antibodies. Treatment of AAV can be divided into the induction phase aimed at achieving remission of the disease and the maintenance phase aimed at prevention of relapses. Long-term outcome of AAV dramatically improved with the introduction of cyclophosphamide. Recent clinical studies resulted in the reduction of the cumulative dose of cyclophosphamide and introduction of new treatment options, namely B-cell-depleting antibody rituximab, into both induction and maintenance treatment. This paper aims to evaluate the current role of the conventional induction and maintenance treatment in view of the gradually increasing use of rituximab. AREAS COVERED: This paper provides an overview of the main clinical studies in induction and maintenance treatment of adult patients with AAV, treatment of relapses of AAV and shortly comments also on the treatment of refractory AAV, treatment of different subgroups of AAV (based on the age, renal function, clinical presentation and type of autoantibody), long-term outcome of patients with AAV, adverse events of treatment and treatment of end-stage renal disease in AAV. EXPERT OPINION: Our analysis demonstrates that although the introduction of rituximab modified the approach to both the induction and maintenance treatment of AAV, more conventional induction and maintenance treatment with standard immunosuppressive drugs still retains its importance as we need more data on long-term efficacy and safety of biologic treatment, and also its cost-effectiveness still remains an open issue. PMID- 26149513 TI - Indian paediatricians ask government to add mumps vaccine to immunisation programme. PMID- 26149515 TI - [Rosenbaum's syndrome]. PMID- 26149516 TI - How do I best manage the care of older patients with cancer with multimorbidity? AB - The typical older patient with cancer presents with several other chronic conditions. The coexistence of multiple chronic conditions in one patient is best termed multimorbidity, and it affects a growing percentage of the population each year. In cancer care, as in much sub-specialty care, "other diseases" have been approached from a research and clinical standpoint as "comorbidities"--other age associated diseases that are of secondary importance to cancer care. This is not the same as the newer concept of "multimorbidity", a situation in which several overlapping chronic conditions are managed as equally-important to patient quality of life and outcomes. In the absence of a substantial evidence base or clinical practice guidelines that are tailored for multimorbid patients, clinicians need practical guidance for a rational approach to care for these complex patients. We adapt the American Geriatrics Society's Guiding Principles as an excellent starting point for clinical decision-making and management. These Guiding Principles include: 1) assessing patient preferences, 2) interpreting the available evidence, 3) estimating prognosis, 4) considering treatment feasibility, and 5) optimizing therapies and care plans. We apply them to older patients with cancer. As the population of older adults with cancer and multimorbidity grows, understanding the impact of multimorbidity on the care of patients with cancer and developing a management approach for these vulnerable patients will be vital for oncology care. PMID- 26149517 TI - Further evidence for very virulent infectious bursal disease virus in vaccinated chickens in Nigeria. AB - Reverse transcription polymerase chain reaction (RT-PCR) and partial sequencing of the VP2 hypervariable region was performed on clinical samples from two infectious bursal disease (IBD) outbreaks in Plateau state, Nigeria. IBD virus RNA was detected in all four bursa of Fabricius samples. Nucleotide sequencing and analysis of the four samples revealed high similarity to previous IBDV sequences from northern and southern Nigeria. The deduced amino acid sequences were compared to reference IBDV strains retrieved from the GenBank; virulence markers A222, I256, and I294 were conserved in both outbreak and reference sequences. Amino acid residue S254 was conserved in the outbreak viruses and previous viruses from northern Nigeria. Phylogenetic analysis revealed that all four viruses were very virulent IBDVs. These viruses clustered with vv2-1 variant viruses from Oyo and Ogun states and less closely with vv2-2 isolates from Tanzania. The nucleotide identity of the sequences in this study ranged from 99.6 to 100 % with each other. These findings are further evidence of IBD outbreaks in vaccinated chicken flocks in Nigeria. PMID- 26149518 TI - Placental elasticity evaluation using virtual touch tissue quantification during pregnancy. AB - INTRODUCTION: Virtual touch tissue quantification (VTTQ) has been developed to evaluate tissue elasticity. Our previous study using delivered placentas showed increased elasticity in fetal growth restriction (FGR). Therefore, we investigated changes in placental elasticity during pregnancy, including complicated pregnancies. METHODS: Based on complications, 199 women were divided into 5 groups (normal, FGR, pregnancy induced hypertension (PIH), diabetes mellitus and collagen disease), and shear wave velocity (SWV) of the placenta, measured using VTTQ, was compared. A cross-sectional study was performed with the 143 normal cases to construct the reference range. The association between placental SWV and the expression ratio of collagen fibers in the placenta stained with Masson's trichrome was determined. RESULTS: The SWV was safely measured for all participants. The correlation between SWV and gestational weeks was not significant. The mean +/- SD SWVs in the normal, FGR, and PIH groups were 0.98 +/ 0.21, 1.28 +/- 0.39, and 1.60 +/- 0.45 m/sec, respectively. The FGR and PIH groups had significantly higher SWVs than that of the normal group. SWV and the expression ratio of collagen fibers were significantly correlated. DISCUSSION: Based on the present findings, changes in SWV during pregnancy were associated with placental fibrosis, and increased SWV in PIH and/or FGR cases might be influenced by infarction, ischemic changes, and inflammation, as well as fibrosis. In conclusion, the measurement of placental SWV is potentially useful to evaluate the condition of the placenta during pregnancy. PMID- 26149519 TI - Efficacy of acupuncture in children with asthma: a systematic review. AB - BACKGROUND: We performed a systematic review of the efficacy of various types of acupuncture in the treatment of asthma in children. METHODS: We searched the MEDLINE, Embase, and Cochrane Library databases up to October 20, 2014. Randomized controlled trials (RCTs) of children and adolescents (<18 years of age) with asthma were included. Data extraction was applied, and methodologic quality was assessed. RESULTS: A total of 32 articles were assessed for eligibility, and seven studies comprising 410 patients were included in the systematic review. Two RCTs showed significant improvement in peak expiratory flow (PEF) variability for acupuncture (traditional and laser) vs. control, with one showing significant improvement in asthma-specific anxiety level, but no significant differences in other lung function parameters or quality of life. Another RCT reported significant benefits of laser acupuncture on lung function parameters but did not describe or report statistical analyses. One crossover RCT showed significant improvements in response to both acupuncture and placebo acupuncture, with better improvements with acupuncture compared to placebo acupuncture (forced exhaled volume in 1 s [FEV1], PEF). Two additional crossover RCTs showed no significant differences between single sessions of laser acupuncture and placebo acupuncture on baseline, postacupuncture, and postinduced bronchoconstriction values (% predicted FEV1, maximum expiratory flow). A recent study showed a significant effect of acupuncture paired with acupressure on medication use and symptoms in preschool-age children. Methodologic and reporting variability remains an issue. However, the results suggest that acupuncture may have a beneficial effect on PEF or PEF variability in children with asthma. CONCLUSIONS: The efficacy of acupuncture on other outcome measures is unclear. Large-scale RCTs are needed to further assess the efficacy of acupuncture in the treatment of asthma in children. PMID- 26149520 TI - Prognostic factors and clinical outcome in patients with surgically resected peripheral N0 adenocarcinoma <3 cm. AB - BACKGROUND: Many reports emphasize the role of sub-lobar resections in the treatment of small peripheral lung cancer. The aim of this study was to investigate a range of prognostic factors, including the extension of resection, which may affect the prognosis in a homogeneous group of patients. METHODS: We retrospectively reviewed the clinical records of 279 patients affected by N0 small peripheral adenocarcinoma (ADK) <3 cm that underwent surgery between 2000 and 2010. Eleven patients were excluded due to non-tumour-related death. RESULTS: There were 176 (66%) males and 92 (34%) females with a median age of 74 years (range 47-93). In the series, 229 (85%) patients received a lobar resection and only 39 (15%) a sub-lobar resection. One hundred ninety-five patients (72%) resulted stage IA while 73 (28%) stage IB. No differences in 5-year survival were observed according to: age (P=0.32), sex (P=0.42), T1a vs. T1b (P=0.31), stage IA vs. IB (P=0.51) and type of resection (P=0.29). Patients affected by ADK with a predominant lepidic growth showed a better 5-year survival (91.3% vs. 81.5%; P=0.044). The multivariate analysis confirmed the growth pattern as an independent risk factor (P=0.048). In patients with visceral pleura infiltration, the sub-lobar resection was associated with a significantly lower 5-year survival compared to lobectomy (63% vs. 90%; P=0.033). The visceral pleural infiltration was independent from ADK growth pattern, predominant lepidic vs. non-lepidic (P=0.51), but it was significantly more frequent in the ADK>2 cm (P=0.012). CONCLUSIONS: Small peripheral (<3 cm) N0 lung ADK can be easily resected by wedge or anatomical segmentectomy. The lepidic growth pattern is the main prognostic factor independently from the extension of resection however, in case of visceral pleural involvement, lobectomy reduces significantly the risk of recurrence. PMID- 26149521 TI - Minimally invasive colorectal surgery: status and technical specifications. AB - Laparoscopy was the most significant technologic advance in colorectal surgery in the last quarter century. The safety, feasibility and oncologic equivalence have been proven, and undisputed clinical benefits have also been demonstrated over open approaches. Despite proven benefits, laparoscopic has not dominated the market, especially for colon and rectal cancer cases. Adaptations in laparoscopic technique were developed to increase use of minimally invasive surgery. Concurrently, there has been a paradigm shift toward less invasive technologies to further optimize patient outcomes. From these needs, hand assisted laparoscopic surgery (HALS), single incision laparoscopic surgery (SILS), and robotic assisted laparoscopic surgery (RALS) were applied to colorectal surgery. Each platform has unique costs and benefits, and similar outcomes when likened to each other in comparative studies. However, conventional laparoscopy, HALS, SILS, and RALS actually serve a complementary role as tools to increase the use of minimally invasive colorectal surgery. The goal of this paper is to review the history, current status, technical specifications, and evolution of the major minimally invasive platforms for colorectal surgery. PMID- 26149522 TI - Updates in abdominal wall management. AB - The field of abdominal wall hernia surgery continues to evolve at a rapid pace. Surgeons dealing with abdominal wall hernias must constantly stay abreast as new biomaterials and surgical techniques evolve. Increasing knowledge related to hernia formation and factors affecting outcomes will help surgeons prevent hernias and individualize hernia repair techniques and biomaterials based on specific clinical situations and patient characteristics. This review outlines some new advances in abdominal wall hernia management focusing on hernia prevention, preoperative strategies to improve outcomes, available biomaterials and mesh products used in hernia repair, new surgical techniques, and improving ways to evaluate outcomes and perform continuous quality improvement in hernia repair. PMID- 26149523 TI - Robotic surgery for thyroid disease. AB - While conventional open thyroidectomy techniques are the most widely performed thyroid operation, they produce an anterior neck scar that may be difficult to conceal. The endoscopic thyroidectomy was developed to decrease the cosmetic impact on the patient and has the advantage of reducing the incidence of anterior neck hypoesthesia and paresthesia. However, this procedure has some drawbacks, which motivated surgeons to develop a new operation method. Robotic thyroidectomy is a relatively new approach for treating differentiated thyroid cancer. Over the last few years, robotic thyroidectomies have become more common. Robotic thyroidectomies are a feasible, safe alternative for managing thyroid disease that has remarkable functional benefits beyond those of conventional open methods. The applications for robotic thyroidectomy have expanded to include increasingly advanced cases, which will consequently change the thyroid surgery paradigm in the future. PMID- 26149524 TI - Psychosurgery (1974-2014). Withdrawals and revivals. New movements and old inspirations. AB - At the Paris Colloquium held forty years ago, and which this paper celebrates, the issue of psychosurgery had not been tackled yet. At that time psychosurgery was tainted by the controversial history of lobotomy and leucotomy. Supporters of psychosurgery at the time of the Colloquium were preparing their fourth International Conference, which was held in Madrid the following year. This represented a key characteristic of the collective, institutional and symbolic action of psychosurgery practitioners. At the end of the seventies, their strategy changed as noted below. Furthermore, we focus on the special importance of the results presented and commented on by psychosurgery supporters, including its conception and classification throughout the rhetoric historically involved (its supposed ventriloquism, its persuasive strength). Based on this view, we suggest a critical reflection encompassing old and new psychosurgery, while questioning the value of new rhetorical devices for the assessment and presentation of psychosurgery results after the surge of Deep Brain Stimulation. PMID- 26149526 TI - Summary and Conclusions. PMID- 26149527 TI - Atomic-resolution dissection of the energetics and mechanism of isomerization of hydrated ATP-Mg(2+) through the SOMA string method. AB - The atomic mechanisms of isomerization of ATP-Mg(2+) in solution are characterized using the recently developed String Method with Optimal Molecular Alignment (SOMA) and molecular-dynamics simulations. Bias-Exchange Metadynamics simulations are first performed to identify the primary conformers of the ATP Mg(2+) complex and their connectivity. SOMA is then used to elucidate the minimum free-energy path (MFEP) for each transition, in a 48-dimensional space. Analysis of the per-atom contributions to the global free-energy profiles reveals that the mechanism of these transitions is controlled by the Mg(2+) ion and its coordinating oxygen atoms in the triphosphate moiety, as well as by the ion hydration shell. Metadynamics simulations in path collective variables based on the MFEP demonstrate these isomerizations proceed across a narrow channel of configurational space, thus validating the premise underlying SOMA. This study provides a roadmap for the examination of conformational changes in biomolecules, based on complementary enhanced-sampling techniques with different strengths. (c) 2015 Wiley Periodicals, Inc. PMID- 26149525 TI - Estrogens and cognition: Friends or foes?: An evaluation of the opposing effects of estrogens on learning and memory. AB - This article is part of a Special Issue "Estradiol and cognition". Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings showing that the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions. PMID- 26149528 TI - Papillary renal cell carcinoma and clear cell renal cell carcinoma: Differentiation of distinct histological types with contrast - enhanced ultrasonography. AB - PURPOSE: Papillary renal cell carcinoma (pRCC) and clear cell renal cell carcinoma (ccRCC) have different biological behaviours and imaging features. The role of contrast-enhanced ultrasound (CEUS) in differentiating these two carcinoma subtypes has not been comprehensively studied. MATERIALS AND METHODS: Forty-eight patients with 49 pRCC lesions and 153 patients with 156 ccRCC lesions underwent preoperative conventional ultrasound (US) and CEUS. Among them, 91 patients (25 pRCCs and 66 ccRCCs) also underwent preoperative contrast-enhanced computed tomography (CECT) in our hospital. The characteristics of CEUS and CECT images for each patient imaged were analysed by each of two blinded observers. RESULTS: Images for five (5/25, 20%) pRCC patients demonstrated equivocal or no enhancement using CECT, while all lesions were enhanced using CEUS. From CEUS, images of pRCCs, when compared with ccRCC images, demonstrated significantly higher frequencies of slow wash-in (59.2% vs. 5.8%), fast wash-out (87.7% vs. 46.1%), and hypo-enhancement (57.1% vs. 7.1%) patterns, p<0.001, as well as the presence of pseudocapsule (42.9% vs. 23.1%), p=0.007. For lesions with large diameters (> 3 cm), a higher percentage of pRCC images demonstrated homogeneous enhancement compared with ccRCC images. Using the combination of slow wash-in, fast wash-out, and hypoenhancement patterns at peak as criteria to differentiate pRCC from ccRCC, positive and negative predictive value, and sensitivity and specificity were found to be 86.7%, 86.9%, 53.1%, and 97.4%, respectively. CONCLUSIONS: CEUS imaging features of slow-in, fast-out, and hypo-enhancement patterns may be useful for differentiating pRCC and ccRCC. In addition, CEUS may be helpful for diagnosing hypovascular renal lesions that demonstrate equivocal or no enhancement by CECT and, thus, for improving diagnostic confidence. PMID- 26149530 TI - A light-up probe with aggregation-induced emission characteristics (AIE) for selective imaging, naked-eye detection and photodynamic killing of Gram-positive bacteria. AB - We report the design and synthesis of a red fluorescent AIE light-up probe for selective recognition, naked-eye detection, and image-guided photodynamic killing of Gram-positive bacteria, including vancomycin-resistant Enterococcus strains. PMID- 26149529 TI - Viable tumor volume: Volume of interest within segmented metastatic lesions, a pilot study of proposed computed tomography response criteria for urothelial cancer. AB - OBJECTIVES: To evaluate the ability of new computed tomography (CT) response criteria for solid tumors such as urothelial cancer (VTV; viable tumor volume) to predict overall survival (OS) in patients with metastatic bladder cancer treated with cabozantinib. MATERIALS AND METHODS: We compared the relative capabilities of VTV, RECIST, MASS (morphology, attenuation, size, and structure), and Choi criteria, as well as volume measurements, to predict OS using serial follow-up contrast-enhanced CT exams in patients with metastatic urothelial carcinoma. Kaplan-Meier curves and 2-tailed log-rank tests compared OS based on early RECIST 1.1 response against each of the other criteria. A Cox proportional hazards model assessed response at follow-up exams as a time-varying covariate for OS. RESULTS: We assessed 141 lesions in 55CT scans from 17 patients with urothelial metastasis, comparing VTV, RECIST, MASS, and Choi criteria, and volumetric measurements, for response assessment. Median follow-up was 4.5 months, range was 2-14 months. Only the VTV criteria demonstrated a statistical association with OS (p=0.019; median OS 9.7 vs. 3.5 months). CONCLUSION: This pilot study suggests that VTV is a promising tool for assessing tumor response and predicting OS, using criteria that incorporate tumor volume and density in patients receiving antiangiogenic therapy for urothelial cancer. Larger studies are warranted to further validate these findings. PMID- 26149531 TI - B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells. AB - A distinct subset of B cells, also known as regulatory B cells, can negatively regulate T cell immune responses, but the role of these cells in schistosomiasis has not been clarified. Soluble egg antigen (SEA) and soluble adult worm antigen preparation (SWAP), which are two important antigen sources during Schistosoma japonicum infection, both can induce Th1, Th2, Th17, and Treg cells and the corresponding cytokines. However, whether they can induce the production of regulatory B cells and the regulatory function of schistosome-induced regulatory B cells remains unclear. In our studies, we first analyzed the production of regulatory B cells stimulated by SEA or SWAP using flow cytometry and enzyme linked immunosorbent assay, and observed these cells in mice immunized by SEA or SWAP. Then, B10 cells sorted by MicroBeads were co-cultured with CD4(+) T cells, and the proportion of Treg cells were detected. At the same time, the IFN-gamma, IL-4, and IL-17 levels in the culture supernatant were measured. The results showed that B10 cells were preferentially induced by SEA in vitro, and B10 could also be induced in mice immunized by SEA. SEA-induced B10 cells promoted the expansion of regulatory T cells and induced IL-4 secretion, but inhibited IL-17 production. These findings reveal that the generation of B10 cells is determined by parasitic antigen, and suggest the function of B10 cell induced by SEA. This study significantly contributes to the understanding of the immune regulatory role in schistosomiasis and may help protect hosts from infection. PMID- 26149532 TI - Acute toxicity and synergistic and antagonistic effects of the aromatic compounds of some essential oils against Culex quinquefasciatus Say larvae. AB - The efficacy of 30 aromatic compounds and their mutual binary combinations was assessed for acute toxicity against the larvae Culex quinquefasciatus. Based on comparison of the lethal doses, thymol and p-cymene were selected as the most effective (LD50 = 18 and 21 mg L(-1), respectively, and LD90 = 25 and 30 mg L( 1), respectively). Although the LD50 for terpinolene and trans-anethole was also estimated at 21 mg L(-1), their LD90 was significantly higher compared to the substances above (245 and 34 mg L(-1), respectively). In total, 435 binary combinations were tested, of which 249 combinations showed a significant synergistic effect, while 74 combinations showed a significant antagonistic effect on mortality. Only nine substances were identified as being able to create a synergistic effect with more than 20 substances: limonene, trans-anethole, 4 allylanisole, carvacrol, isoeugenol, menthone, carvone, borneol, and camphor. The highest synergistic effect on larval mortality was achieved for the combinations: eugenol and isoeugenol, carvone and carvacrol, carvone and 4-allylanisole, carvone and alpha-terpineol, carvone and menthone, limonene and trans-anethole, limonene and menthone, alpha-pinene and menthone, beta-citronellol and menthone, carvacrol and 4-allylanisole, carvacrol and terpineol, alpha-terpinene and trans anethole, camphor and menthone, camphene and menthone, and 4-allylanisole and menthone. Significant differences between achieved mortality and the mutual mixing ratio were found for the five selected binary mixtures that had shown the most significant synergistic effect in the previous tests. The mixture of limonene and trans-anethole showed the highest mortality, with the mixing ratio 1:1; the mixture of eugenol and isoeugenol caused 90.2% mortality, with the mixing ratio 1:3. One hundred percent mortality was achieved if carvacrol was contained in a mixture with carvone in a ratio >2. After a comparison of all our results, based on our experiments, we can choose two pairs that caused mortality higher than 90% in concentrations lower than 20 mg L(-1): limonene and trans anethole (with the mixing ratio 1:1), and carvone and carvacrol (with the mixing ratio 1:2-3). The information gained can thus be used in the development of new botanical insecticides based on essential oils (EOs) and particularly in the creation of formulations. PMID- 26149533 TI - Stachybisbins A and B, the first cases of seco-bisabosquals from Stachybotrys bisbyi. AB - Stachybisbins A (1) and B (2), two new meroterpenoids with unprecedented seco bisabosqual skeleton, together with three biogenetically related metabolites (3 5), were isolated from a wetland fungal strain of Stachybotrys bisbyi. The structures of the new compounds were determined by spectroscopic analyses, modified Mosher's method, and quantum chemical CD method. The cytotoxic activities of all compounds were tested against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines. PMID- 26149535 TI - Insights into the mechanism of extraction of uranium (VI) from nitric acid solution into an ionic liquid by using tri-n-butyl phosphate. AB - We present new results on the liquid-liquid extraction of uranium (VI) from a nitric acid aqueous phase into a tri-n-butyl phosphate/1-butyl-3 methylimidazolium bis(trifluoromethylsulfonyl)imide (TBP/[C4 mim][Tf2 N]) phase. The individual solubilities of the ionic-liquid ions in the upper part of the biphasic system are measured over the whole acidic range and as a function of the TBP concentration. New insights into the extraction mechanism are obtained through the in situ characterization of the extracted uranyl complexes by coupling UV/Vis and extended X-ray absorption fine structure (EXAFS) spectroscopy. We propose a chemical model to explain uranium (VI) extraction that describes the data through a fit of the uranyl distribution ratio DU . In this model, at low acid concentrations uranium (VI) is extracted as the cationic complex [UO2 (TBP)2 ](2+) , by an exchange with one proton and one C4 mim(+) . At high acid concentrations, the extraction proceeds through a cationic exchange between [UO2 (NO3 )(HNO3 )(TBP)2 ](+) and one C4 mim(+) . As a consequence of this mechanism, the variation of DU as a function of TBP concentration depends on the C4 mim(+) concentration in the aqueous phase. This explains why noninteger values are often derived by analysis of DU versus [TBP] plots to determine the number of TBP molecules involved in the extraction of uranyl in an ionic-liquid phase. PMID- 26149534 TI - Second allogeneic hematopoietic cell transplantation for graft failure: poor outcomes for neutropenic graft failure. AB - Graft failure (GF) after hematopoietic cell transplant (HCT) occurs in 5-30% of patients. GF can be accompanied by neutropenia (NGF) or can result with adequate neutrophils, but loss of donor chimerism (non-neutropenic graft failure, NNGF). In this report, we describe the outcomes of 95 patients treated with a second HCT for GF at the University of Minnesota; 62 with NGF and 33 with NNGF. The cumulative incidence of neutrophil recovery at 42 days after second HCT was 45% for NGF and 88% for NNGF. A second GF occurred in 34 NGF (55%) and in 9 NNGF (27%) patients. The incidence of Grade III-IV acute graft versus host disease (GVHD) was 8% (95% confidence interval (CI), 1-16%) and 12% (95% CI, 1-23%) for NGF and NNGF, respectively. From the 2nd HCT, 1-year overall survival (OS) was 44% (95% CI, 34-54%), [NNGF: 76% (95% CI, 57-87%) and NGF: 27% (95% CI, 17-39%)]. The most common cause of death after second HCT was infection (52%). In summary, the outcomes of second HCT after NGF and NNGF are different with much worse outcomes for NGF necessitating new approaches for this complication. PMID- 26149537 TI - Interactions between the intestinal microbiota and bile acids in gallstones patients. AB - Cholecystectomy, surgical removal of the gallbladder, changes bile flow to the intestine and can therefore alter the bidirectional interactions between bile acids (BAs) and the intestinal microbiota. We quantified and correlated BAs and bacterial community composition in gallstone patients scheduled for cholecystectomy before and after the procedure, using gas-liquid chromatography and 16S rRNA amplicon sequencing, followed by quantitative real-time polymerase chain reaction of the phylum Bacteroidetes. Gallstone patients had higher overall concentrations of faecal BAs and a decreased microbial diversity, accompanied by a reduction in the beneficial genus Roseburia and an enrichment of the uncultivated genus Oscillospira, compared with controls. These two genera may thus serve as biomarkers for symptomatic gallstone formation. Oscillospira was correlated positively with secondary BAs and negatively with primary BAs, while the phylum Bacteroidetes showed an opposite trend. Cholecystectomy resulted in no substantial change in patients' faecal BAs. However, bacterial composition was significantly altered, with a significant increase in the phylum Bacteroidetes. Given that cholecystectomy has been associated with a higher risk of colorectal cancer and that members of the Bacteroidetes are increased in that disease, microbial consequences of cholecystectomy should be further explored. PMID- 26149536 TI - Antimicrobial activity of synthetic cationic peptides and lipopeptides derived from human lactoferricin against Pseudomonas aeruginosa planktonic cultures and biofilms. AB - BACKGROUND: Infections by Pseudomonas aeruginosa constitute a serious health threat because this pathogen -particularly when it forms biofilms - can acquire resistance to the majority of conventional antibiotics. This study evaluated the antimicrobial activity of synthetic peptides based on LF11, an 11-mer peptide derived from human lactoferricin against P. aeruginosa planktonic and biofilm forming cells. We included in this analysis selected N-acylated derivatives of the peptides to analyze the effect of acylation in antimicrobial activity. To assess the efficacy of compounds against planktonic bacteria, microdilution assays to determine the minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill studies were conducted. The anti biofilm activity of the agents was assessed on biofilms grown under static (on microplates) and dynamic (in a CDC-reactor) flow regimes. RESULTS: The antimicrobial activity of lipopeptides differed from that of non-acylated peptides in their killing mechanisms on planktonic and biofilm-forming cells. Thus, acylation enhanced the bactericidal activity of the parental peptides and resulted in lipopeptides that were uniformly bactericidal at their MIC. In contrast, acylation of the most potent anti-biofilm peptides resulted in compounds with lower anti-biofilm activity. Both peptides and lipopeptides displayed very rapid killing kinetics and all of them required less than 21 min to reduce 1,000 times the viability of planktonic cells when tested at 2 times their MBC. The peptides, LF11-215 (FWRIRIRR) and LF11-227 (FWRRFWRR), displayed the most potent anti-biofilm activity causing a 10,000 fold reduction in cell viability after 1 h of treatment at 10 times their MIC. At that concentration, these two compounds exhibited low citotoxicity on human cells. In addition to its bactericidal activity, LF11-227 removed more that 50 % of the biofilm mass in independent assays. Peptide LF11-215 and two of the shortest and least hydrophobic lipopeptides, DI-MB-LF11-322 (2,2-dimethylbutanoyl-PFWRIRIRR) and DI MB-LF11-215, penetrated deep into the biofilm structure and homogenously killed biofilm-forming bacteria. CONCLUSION: We identified peptides derived from human lactoferricin with potent antimicrobial activity against P. aeruginosa growing either in planktonic or in biofilm mode. Although further structure-activity relationship analyses are necessary to optimize the anti-biofilm activity of these compounds, the results indicate that lactoferricin derived peptides are promising anti-biofilm agents. PMID- 26149539 TI - Experimental Dermatology launches a new type of manuscript: 'BEDSIDE-TO-BENCH LETTER'. PMID- 26149538 TI - Patterns of acetaminophen medication use associated with exceeding the recommended maximum daily dose. AB - BACKGROUND: Acetaminophen overuse has been linked to liver injury. PURPOSE: To identify patterns of medication use associated with exceeding the recommended daily maximum dose of 4 g acetaminophen. METHODS: Respondents from a national panel completed a detailed daily medication diary online for 7 days (n = 5649), identifying medications taken from a comprehensive list of over-the-counter (OTC) and prescription (Rx) acetaminophen medications. Respondents were not told the study concerned acetaminophen. Total daily intake was calculated from diary data. Generalized estimating equations assessed the association of medication patterns with exceeding 4 g per day among 3618 respondents who used acetaminophen medications (on 13,852 days) during the diary period. RESULTS: Acetaminophen intake exceeded 4 g on 3.1% of usage days; median intake on those days was 5.5 g. As expected, days when intake exceeded 4 g were almost always (92%) marked by deviations from label directions-exceeding the one-time dose, re-dosing too soon, and concomitant use of multiple acetaminophen medications. Re-dosing too soon was the most frequent deviation, and concomitant use was most strongly tied to exceeding the daily limit. Use of both an Rx and an OTC medication on the same day also increased the odds of exceeding 4 g on days when concomitant use occurred. CONCLUSIONS: Excess dosing of acetaminophen is associated with deviations from label directions and by use of both OTC and Rx medications containing acetaminophen within a single concomitant use day. PMID- 26149540 TI - Pituitary volume and clinical trajectory in young relatives at risk for schizophrenia. AB - BACKGROUND: Stress and vulnerability likely interact to play a major role in psychosis. While much has been written about the neural diathesis-stress model in psychosis and its clinical risk states, little is known about HPA axis biomarkers in non-help-seeking individuals at familial high risk (FHR). We sought to prospectively measure pituitary volume (PV) in adolescents and young adults at FHR for schizophrenia and to follow their emerging sub-clinical psychotic symptoms and clinical trajectories. METHOD: Forty healthy controls and 38 relatives of patients with schizophrenia or schizoaffective disorder were identified in Pittsburgh, USA. PV was derived from baseline 1.5 T magnetic resonance imaging. Chapman's schizotypy scales were acquired at baseline, and structured clinical interviews for DSM-IV-TR Axis I diagnoses were attempted annually for up to 3 years. RESULTS: Seven individuals converted to psychosis. PV did not differ between FHR and control groups overall. Within the FHR group, PV was positively correlated with Chapman's positive schizotypy (Magical Ideation and Perceptual Aberration) scores, and there was a significant group * PV interaction with schizotypy. PV was significantly higher in FHR subjects carrying any baseline Axis I diagnosis (p = 0.004), and higher still in individuals who went on to convert to psychosis (p = 0.0007). CONCLUSIONS: Increased PV is a correlate of early positive schizotypy, and may predict trait vulnerability to subsequent psychosis in FHR relatives. These preliminary findings support a model of stress-vulnerability and HPA axis activation in the early phases of psychosis. PMID- 26149541 TI - Correlation of serum and dried blood spot results for quantitation of Schistosoma circulating anodic antigen: a proof of principle. AB - Circulating anodic antigen (CAA) testing is a powerful, increasingly-used tool for diagnosis of active schistosome infection. We sought to determine the feasibility and reliability of measuring CAA in blood spots collected on Whatman 903 protein saver cards, which are the predominant filter papers used worldwide for dried blood spot (DBS) research and clinical care. CAA was eluted from blood spots collected from 19 individuals onto Whatman 903 cards in Mwanza, Tanzania, and the assay was optimized to achieve CAA ratios comparable to those obtained from the spots' corresponding serum samples. The optimized assay was then used to determine the correlation of serum samples (n=16) with DBS from cards that had been stored for 8 years at ambient temperature. Using a DBS volume equivalent to approximately four times the quantity of serum, CAA testing in DBS had a sensitivity of 76% and a specificity of 79% compared to CAA testing in serum. CAA testing was reliable in samples eluted from Whatman 903 cards that had been stored for 8 years at ambient temperature. The overall kappa coefficient was 0.53 (standard error 0.17, p<0.001). We conclude that CAA can be reliably and accurately measured in DBS collected onto the filter paper that is most commonly used for clinical care and research, and that can be stored from prolonged periods of time. This finding opens new avenues for future work among more than 700million individuals living in areas worldwide in which schistosomes are endemic. PMID- 26149543 TI - Subungual Congenital Nevus with Recurrent Nevus Phenomenon. AB - Melanonychia is uncommon. We report the first case of histopathologic recurrence of a completely excised subungual congenital nevus that presented as congenital melanonychia. PMID- 26149542 TI - Disruption of the Arabidopsis Defense Regulator Genes SAG101, EDS1, and PAD4 Confers Enhanced Freezing Tolerance. AB - In Arabidopsis, three lipase-like regulators, SAG101, EDS1, and PAD4, act downstream of resistance protein-associated defense signaling. Although the roles of SAG101, EDS1, and PAD4 in biotic stress have been extensively studied, little is known about their functions in plant responses to abiotic stresses. Here, we show that SAG101, EDS1, and PAD4 are involved in the regulation of freezing tolerance in Arabidopsis. With or without cold acclimation, the sag101, eds1, and pad4 single mutants, as well as their double mutants, exhibited similarly enhanced tolerance to freezing temperatures. Upon cold exposure, the sag101, eds1, and pad4 mutants showed increased transcript levels of C-REPEAT/DRE BINDING FACTORs and their regulons compared with the wild type. Moreover, freezing induced cell death and accumulation of hydrogen peroxide were ameliorated in sag101, eds1, and pad4 mutants. The sag101, eds1, and pad4 mutants had much lower salicylic acid (SA) and diacylglycerol (DAG) contents than the wild type, and exogenous application of SA and DAG compromised the freezing tolerance of the mutants. Furthermore, SA suppressed the cold-induced expression of DGATs and DGKs in the wild-type leaves. These findings indicate that SAG101, EDS1, and PAD4 are involved in the freezing response in Arabidopsis, at least in part, by modulating the homeostasis of SA and DAG. PMID- 26149545 TI - There Is No Such Thing as a "Positive" Antibody Test: Diagnosing Heparin-Induced Thrombocytopenia in 2015. PMID- 26149544 TI - Trapped lipopolysaccharide and LptD intermediates reveal lipopolysaccharide translocation steps across the Escherichia coli outer membrane. AB - Lipopolysaccharide (LPS) is a main component of the outer membrane of Gram negative bacteria, which is essential for the vitality of most Gram-negative bacteria and plays a critical role for drug resistance. LptD/E complex forms a N terminal LPS transport slide, a hydrophobic intramembrane hole and the hydrophilic channel of the barrel, for LPS transport, lipid A insertion and core oligosaccharide and O-antigen polysaccharide translocation, respectively. However, there is no direct evidence to confirm that LptD/E transports LPS from the periplasm to the external leaflet of the outer membrane. By replacing LptD residues with an unnatural amino acid p-benzoyl-L-phenyalanine (pBPA) and UV photo-cross-linking in E.coli, the translocon and LPS intermediates were obtained at the N-terminal domain, the intramembrane hole, the lumenal gate, the lumen of LptD channel, and the extracellular loop 1 and 4, providing the first direct evidence and "snapshots" to reveal LPS translocation steps across the outer membrane. PMID- 26149546 TI - Size and How You Measure It Matters. PMID- 26149547 TI - Admitting What We Do Not Know About Pneumonia Readmissions. PMID- 26149548 TI - The Civil Liberty of Smoking Cigarettes. PMID- 26149549 TI - POINT: Should Small-Bore Pleural Catheter Placement Be the Preferred Initial Management for Malignant Pleural Effusions? Yes. PMID- 26149550 TI - COUNTERPOINT: Should Small-Bore Pleural Catheter Placement Be the Preferred Initial Management for Malignant Pleural Effusions? No. PMID- 26149551 TI - Rebuttal From Drs Lee and Feller-Kopman. PMID- 26149552 TI - Rebuttal From Drs Gillespie and DeCamp. PMID- 26149553 TI - Management of Idiopathic Pulmonary Fibrosis in the Elderly Patient: Addressing Key Questions. AB - Idiopathic pulmonary fibrosis (IPF) is strongly associated with advanced age. Making an accurate diagnosis of IPF is critical, as it remains only one of many potential diagnoses for an elderly patient with newly recognized interstitial lung disease. Optimal management of IPF, especially in older-aged patients, hinges on such factors as balancing the application of standard-of-care measures with the patient's overall health status (robustness vs frailty) and considering the patient's wishes, desires, and expectations. IPF is known to be associated with certain comorbidities that tend to be more prevalent in the elderly population. Until recently, options for the pharmacologic management of IPF were limited and included therapies such as immunosuppressive agents, which may pose substantial risk to the elderly patient. However, the antifibrotic agents pirfenidone and nintedanib have now become commercially available in the United States for the treatment of IPF. The monitoring and treatment of patients with IPF, especially elderly patients with comorbid medical conditions, require consideration of adverse side effects, the avoidance of potential drug-drug interactions, treatment of comorbidities, and the timely implementation of supportive and palliative measures. Individualized counseling to guide decision making and enhance quality of life is also integral to optimal management of the elderly patient with IPF. PMID- 26149555 TI - Necrotic Tuberculin Skin (Mantoux) Test Reaction: A Case Report and an Estimation of Frequency. AB - Tuberculin skin testing was performed on a 5-year-old girl in Phnom Penh, Cambodia. She had been immunized by Bacille de Calmette et Guerin. She was tested because of a palpable cervical node and a slightly elevated temperature. Within 48 h, a deep necrotic lesion appeared on the volar aspect of the left arm. The lesion was treated locally, and the child was not treated for suspected TB. To our knowledge, this is the first instance of necrosis in 11,392 people who received Tubersol doses since 1996 to date at our International Vaccination Center, for an estimated incidence of 0.18 per 1,000 (95% Poisson 0.04-0.70 per 1,000 doses used). At a follow-up consultation after 77 days, the lesion had scarred and the child showed no signs suggestive of active TB. Although latent TB infection remains the most likely diagnosis, other types of mycobacterial infection may be considered in the tropical setting and in the absence of signs suggestive of active TB. PMID- 26149556 TI - A 50-Year-Old Man Presenting With Cough and an Endobronchial Lesion After Initiation of Highly Active Antiretroviral Therapy. PMID- 26149554 TI - Central Disorders of Hypersomnolence: Focus on the Narcolepsies and Idiopathic Hypersomnia. AB - The central disorders of hypersomnolence are characterized by severe daytime sleepiness, which is present despite normal quality and timing of nocturnal sleep. Recent reclassification distinguishes three main subtypes: narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia (IH), which are the focus of this review. Narcolepsy type 1 results from loss of hypothalamic hypocretin neurons, while the pathophysiology underlying narcolepsy type 2 and IH remains to be fully elucidated. Treatment of all three disorders focuses on the management of sleepiness, with additional treatment of cataplexy in those patients with narcolepsy type 1. Sleepiness can be treated with modafinil/armodafinil or sympathomimetic CNS stimulants, which have been shown to be beneficial in randomized controlled trials of narcolepsy and, quite recently, IH. In those patients with narcolepsy type 1, sodium oxybate is effective for the treatment of both sleepiness and cataplexy. Despite these treatments, there remains a subset of hypersomnolent patients with persistent sleepiness, in whom alternate therapies are needed. Emerging treatments for sleepiness include histamine H3 antagonists (eg, pitolisant) and possibly negative allosteric modulators of the gamma-aminobutyric acid-A receptor (eg, clarithromycin and flumazenil). PMID- 26149557 TI - A 22-Year-Old Nonsmoker With Diffuse Cystic Lung Disease. AB - A 22-year-old previously healthy woman was evaluated in pulmonary clinic for shortness of breath and cough that had been slowly progressive over 3 months. She otherwise reported being fully functional and attended her college graduation a week prior to evaluation. She had no history of smoking, illicit drug use, connective tissue disease, or noxious exposures. PMID- 26149558 TI - A 38-Year-Old Man With Obesity, Intermittent Tachycardia, and One Episode of Syncope. AB - A 38-year-old man with history of diabetes, hypertension, hyperlipidemia, and obesity was referred to the electrophysiology clinic for evaluation of infrequent palpitations and remote history of syncope. The patient described a sensation of racing of the heart, which lasted about 30 min to 1 h and occurred several times over the past year. This was associated with a sense of anxiety and shortness of breath and appeared to resolve spontaneously. The patient also experienced one episode of syncope in the past while enjoying a barbecue on a hot summer day. He did not recall if this episode was accompanied by palpitations, however, the previously mentioned symptoms prompted the consultation. Upon further questioning the patient also reported experiencing fatigue. He stated that he noted decreased energy and frequent daytime sleepiness. PMID- 26149559 TI - Assessment of Ventilation During the Performance of Elective Endoscopic-Guided Percutaneous Tracheostomy: What's New 10 Years Later? PMID- 26149560 TI - Response. PMID- 26149561 TI - Electronic Cigarettes: The Resistance Value of the Heating Filament Could Be the Key to Lung Toxicity. PMID- 26149562 TI - Response. PMID- 26149563 TI - Roflumilast in COPD. PMID- 26149564 TI - Response. PMID- 26149565 TI - CT Scan Segmental Airway Lumen Area. PMID- 26149566 TI - Response. PMID- 26149567 TI - A Man in His 60s With Cirrhosis, Encephalopathy, and Shock. PMID- 26149568 TI - A 70-Year-Old Man With Large Cervical and Mediastinal Lymphadenopathies. AB - We present a case of a 70-year-old man with enlarged mediastinal and cervical lymph nodes that provided interesting radiologic and pathologic observations. The 70-year-old black man was found to have enlarged mediastinal lymph nodes. He had symptoms of atypical chest pain and generalized weakness for 2 weeks prior to the diagnosis. He denied shortness of breath, fever, chills, or night sweats. He was treated for hypertension and onychomycosis. Basic laboratory findings were within normal limits. Pulmonary function tests at the time of presentation showed FEV1, FVC, and FEV1/FVC ratio of 123% predicted, 133% predicted, and 0.7, respectively. Meanwhile, total lung capacity and carbon monoxide diffusing capacity were 103% and 107% predicted, respectively. Two weeks before he presented to our institution, the patient underwent bronchoscopy with transbronchial biopsies of the right lower lobe and endobronchial ultrasound-guided transbronchial needle aspiration of the right hilar lymph nodes. PMID- 26149569 TI - Sequence Motifs in Transit Peptides Act as Independent Functional Units and Can Be Transferred to New Sequence Contexts. AB - A large number of nuclear-encoded proteins are imported into chloroplasts after they are translated in the cytosol. Import is mediated by transit peptides (TPs) at the N termini of these proteins. TPs contain many small motifs, each of which is critical for a specific step in the process of chloroplast protein import; however, it remains unknown how these motifs are organized to give rise to TPs with diverse sequences. In this study, we generated various hybrid TPs by swapping domains between Rubisco small subunit (RbcS) and chlorophyll a/b-binding protein, which have highly divergent sequences, and examined the abilities of the resultant TPs to deliver proteins into chloroplasts. Subsequently, we compared the functionality of sequence motifs in the hybrid TPs with those of wild-type TPs. The sequence motifs in the hybrid TPs exhibited three different modes of functionality, depending on their domain composition, as follows: active in both wild-type and hybrid TPs, active in wild-type TPs but inactive in hybrid TPs, and inactive in wild-type TPs but active in hybrid TPs. Moreover, synthetic TPs, in which only three critical motifs from RbcS or chlorophyll a/b-binding protein TPs were incorporated into an unrelated sequence, were able to deliver clients to chloroplasts with a comparable efficiency to RbcS TP. Based on these results, we propose that diverse sequence motifs in TPs are independent functional units that interact with specific translocon components at various steps during protein import and can be transferred to new sequence contexts. PMID- 26149570 TI - Transcription Factor Arabidopsis Activating Factor1 Integrates Carbon Starvation Responses with Trehalose Metabolism. AB - Plants respond to low carbon supply by massive reprogramming of the transcriptome and metabolome. We show here that the carbon starvation-induced NAC (for NO APICAL MERISTEM/ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR/CUP-SHAPED COTYLEDON) transcription factor Arabidopsis (Arabidopsis thaliana) Transcription Activation Factor1 (ATAF1) plays an important role in this physiological process. We identified TREHALASE1, the only trehalase-encoding gene in Arabidopsis, as a direct downstream target of ATAF1. Overexpression of ATAF1 activates TREHALASE1 expression and leads to reduced trehalose-6-phosphate levels and a sugar starvation metabolome. In accordance with changes in expression of starch biosynthesis- and breakdown-related genes, starch levels are generally reduced in ATAF1 overexpressors but elevated in ataf1 knockout plants. At the global transcriptome level, genes affected by ATAF1 are broadly associated with energy and carbon starvation responses. Furthermore, transcriptional responses triggered by ATAF1 largely overlap with expression patterns observed in plants starved for carbon or energy supply. Collectively, our data highlight the existence of a positively acting feedforward loop between ATAF1 expression, which is induced by carbon starvation, and the depletion of cellular carbon/energy pools that is triggered by the transcriptional regulation of downstream gene regulatory networks by ATAF1. PMID- 26149571 TI - Flowering Locus C's Lessons: Conserved Chromatin Switches Underpinning Developmental Timing and Adaptation. AB - Analysis of how seasonal cues influence the timing of the floral transition has revealed many important principles for how epigenetic regulation can integrate a variety of environmental cues with developmental signals. The study of the pathways that necessitate overwintering in plants and their ability to respond to prolonged cold (the vernalization requirement and response pathways) has elaborated different chromatin regulatory pathways and the involvement of noncoding RNAs. The major target of these vernalization pathways in Arabidopsis (Arabidopsis thaliana) is Flowering Locus C (FLC). A relatively simple picture of FLC regulation is emerging of a few core complexes and mechanisms that antagonize each other's actions. This balance provides a fine degree of control that has nevertheless permitted evolution of a wide range of natural variation in vernalization in Arabidopsis. Similar simple routes of adaptation may underlie life history variation between species. PMID- 26149572 TI - Trans-Homolog Interactions Facilitating Paramutation in Maize. AB - Paramutations represent locus-specific trans-homolog interactions affecting the heritable silencing properties of endogenous alleles. Although examples of paramutation are well studied in maize (Zea mays), the responsible mechanisms remain unclear. Genetic analyses indicate roles for plant-specific DNA-dependent RNA polymerases that generate small RNAs, and current working models hypothesize that these small RNAs direct heritable changes at sequences often acting as transcriptional enhancers. Several studies have defined specific sequences that mediate paramutation behaviors, and recent results identify a diversity of DNA dependent RNA polymerase complexes operating in maize. Other reports ascribe broader roles for some of these complexes in normal genome function. This review highlights recent research to understand the molecular mechanisms of paramutation and examines evidence relevant to small RNA-based modes of transgenerational epigenetic inheritance. PMID- 26149573 TI - A Comparative Epigenomic Analysis of Polyploidy-Derived Genes in Soybean and Common Bean. AB - Soybean (Glycine max) and common bean (Phaseolus vulgaris) share a paleopolyploidy (whole-genome duplication [WGD]) event, approximately 56.5 million years ago, followed by a genus Glycine-specific polyploidy, approximately 10 million years ago. Cytosine methylation is an epigenetic mark that plays an important role in the regulation of genes and transposable elements (TEs); however, the role of DNA methylation in the fate/evolution of genes following polyploidy and speciation has not been fully explored. Whole-genome bisulfite sequencing was used to produce nucleotide resolution methylomes for soybean and common bean. We found that, in soybean, CG body-methylated genes were abundant in WGD genes, which were, on average, more highly expressed than single-copy genes and had slower evolutionary rates than unmethylated genes, suggesting that WGD genes evolve more slowly than single-copy genes. CG body-methylated genes were also enriched in shared single-copy genes (single copy in both species) that may be responsible for the broad and high expression patterns of this class of genes. In addition, diverged methylation patterns in non-CG contexts between paralogs were due mostly to TEs in or near genes, suggesting a role for TEs and non-CG methylation in regulating gene expression post polyploidy. Reference methylomes for both soybean and common bean were constructed, providing resources for investigating epigenetic variation in legume crops. Also, the analysis of methylation patterns of duplicated and single-copy genes has provided insights into the functional consequences of polyploidy and epigenetic regulation in plant genomes. PMID- 26149574 TI - Ethylene Inhibits Cell Proliferation of the Arabidopsis Root Meristem. AB - The root system of plants plays a critical role in plant growth and survival, with root growth being dependent on both cell proliferation and cell elongation. Multiple phytohormones interact to control root growth, including ethylene, which is primarily known for its role in controlling root cell elongation. We find that ethylene also negatively regulates cell proliferation at the root meristem of Arabidopsis (Arabidopsis thaliana). Genetic analysis indicates that the inhibition of cell proliferation involves two pathways operating downstream of the ethylene receptors. The major pathway is the canonical ethylene signal transduction pathway that incorporates CONSTITUTIVE TRIPLE RESPONSE1, ETHYLENE INSENSITIVE2, and the ETHYLENE INSENSITIVE3 family of transcription factors. The secondary pathway is a phosphorelay based on genetic analysis of receptor histidine kinase activity and mutants involving the type B response regulators. Analysis of ethylene-dependent gene expression and genetic analysis supports SHORT HYPOCOTYL2, a repressor of auxin signaling, as one mediator of the ethylene response and furthermore, indicates that SHORT HYPOCOTYL2 is a point of convergence for both ethylene and cytokinin in negatively regulating cell proliferation. Additional analysis indicates that ethylene signaling contributes but is not required for cytokinin to inhibit activity of the root meristem. These results identify key elements, along with points of cross talk with cytokinin and auxin, by which ethylene negatively regulates cell proliferation at the root apical meristem. PMID- 26149575 TI - Rate Motifs Tune Auxin/Indole-3-Acetic Acid Degradation Dynamics. AB - Ubiquitin-mediated protein degradation is a common feature in diverse plant cell signaling pathways; however, the factors that control the dynamics of regulated protein turnover are largely unknown. One of the best-characterized families of E3 ubiquitin ligases facilitates ubiquitination of auxin (aux)/indole-3-acetic acid (IAA) repressor proteins in the presence of auxin. Rates of auxin-induced degradation vary widely within the Aux/IAA family, and sequences outside of the characterized degron (the minimum region required for auxin-induced degradation) can accelerate or decelerate degradation. We have used synthetic auxin degradation assays in yeast (Saccharomyces cerevisiae) and in plants to characterize motifs flanking the degron that contribute to tuning the dynamics of Aux/IAA degradation. The presence of these rate motifs is conserved in phylogenetically distant members of the Arabidopsis (Arabidopsis thaliana) Aux/IAA family, as well as in their putative Brassica rapa orthologs. We found that rate motifs can act by enhancing interaction between repressors and the E3, but that this is not the only mechanism of action. Phenotypes of transgenic plants expressing a deletion in a rate motif in IAA28 resembled plants expressing degron mutations, underscoring the functional relevance of Aux/IAA degradation dynamics in regulating auxin responses. PMID- 26149576 TI - Abscisic Acid Is a General Negative Regulator of Arabidopsis Axillary Bud Growth. AB - Branching is an important process controlled by intrinsic programs and by environmental signals transduced by a variety of plant hormones. Abscisic acid (ABA) was previously shown to mediate Arabidopsis (Arabidopsis thaliana) branching responses to the ratio of red light (R) to far-red light (FR; an indicator of competition) by suppressing bud outgrowth from lower rosette positions under low R:FR. However, the role of ABA in regulating branching more generally was not investigated. This study shows that ABA restricts lower bud outgrowth and promotes correlative inhibition under both high and low R:FR. ABA was elevated in buds exhibiting delayed outgrowth resulting from bud position and low R:FR and decreased in elongating buds. ABA was reduced in lower buds of hyperbranching mutants deficient in auxin signaling (AUXIN RESISTANT1), MORE AXILLARY BRANCHING (MAX) signaling (MAX2), and BRANCHED1 (BRC1) function, and partial suppression of branch elongation in these mutants by exogenous ABA suggested that ABA may act downstream of these components. Bud BRC1 expression was not altered by exogenous ABA, consistent with a downstream function for ABA. However, the expression of genes encoding the indole-3-acetic acid (IAA) biosynthesis enzyme TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS1, the auxin transporter PIN-FORMED1, and the cell cycle genes CYCLIN A2;1 and PROLIFERATING CELL NUCLEAR ANTIGEN1 in buds was suppressed by ABA, suggesting that it may inhibit bud growth in part by suppressing elements of the cell cycle machinery and bud-autonomous IAA biosynthesis and transport. ABA was found to suppress bud IAA accumulation, thus confirming this aspect of its action. PMID- 26149578 TI - Culture temperature modulates monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures. AB - OBJECTIVE: To investigate the effect of lowering culture temperature on monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures. RESULTS: In both batch and fed-batch cultures, lowering the culture temperature decreased the antibody acidic variant levels. The acidic variant levels (defined as variants eluting earlier than the main peak of an antibody during HPLC) at 32 degrees C were about 10 % lower than those at 37 degrees C at the end of both batch and fed-batch cultures. Additionally, lowering the culture temperature increased the lysine variant level, which further increased basic variant level. The lysine variant levels at 32 degrees C were about 8 % (batch culture) and 3 % (fed-batch culture) higher than those at 37 degrees C at the end of cultures. Real-time PCR results suggests that the decrease in carboxypeptidase B transcription level might be partially responsible for the increased lysine variant level at sub-physiological temperatures. CONCLUSION: Culture temperature exhibits noticeable impact on antibody charge variation distribution, especially the acidic variants and lysine variants. PMID- 26149577 TI - Cross-sectional examination of metabolites and metabolic phenotypes in uremia. AB - BACKGROUND: Although metabolomic approaches have begun to document numerous changes that arise in end stage renal disease (ESRD), how these alterations relate to established metabolic phenotypes in uremia is unknown. METHODS: In 200 incident hemodialysis patients we used partial least squares discriminant analysis to identify which among 166 metabolites could best discriminate individuals with or without diabetes, and across tertiles of body mass index, serum albumin, total cholesterol, and systolic blood pressure. RESULTS: Our data do not recapitulate metabolomic signatures of diabetes and obesity identified among individuals with normal renal function (e.g. elevations in branched chain and aromatic amino acids) and highlight several potential markers of diabetes status specific to ESRD, including xanthosine-5-phosphate and vanillylmandelic acid. Further, our data identify significant associations between elevated tryptophan and long-chain acylcarnitine levels and both decreased total cholesterol and systolic blood pressure in ESRD. Higher tryptophan levels were also associated with higher serum albumin levels, but this may reflect tryptophan's significant albumin binding. Finally, an examination of the uremic retention solutes captured by our platform in relation to 24 clinical phenotypes provides a framework for investigating mechanisms of uremic toxicity. CONCLUSIONS: In sum, these studies leveraging metabolomic and metabolic phenotype data acquired in a well-characterized ESRD cohort demonstrate striking differences from metabolomics studies in the general population, and may provide clues to novel functional pathways in the ESRD population. PMID- 26149579 TI - Novel properties of gamma-glutamyltransferase from Pseudomonas syringae with beta aspartyltransferase activity. AB - OBJECTIVES: Gene cloning, purification, and characterization of gamma glutamyltransferase from Pseudomonas syringae (PsGGT) were performed in Escherichia coli. RESULTS: PsGGT was partially purified to 13-fold, with a specific activity of 0.92 U/mg. The molecule is presumed to be a heterodimeric consisting of large (37 kDa) and small (21 kDa) subunits. The optimal pH and temperature for hydrolytic activity were 8 and 37 degrees C, and those for transfer activity were 9 and 50 degrees C, respectively. PsGGT could transfer beta-aspartyl moiety from asparagine to hydroxylamine and the gamma-glutamyl moiety from glutamine to hydroxylamine. CONCLUSION: PsGGT demonstrated novel functionality on both gamma-glutamyltransferase and beta-aspartyltransferase. PMID- 26149580 TI - Molecular pharming's foot in the FDA's door: Protalix's trailblazing story. AB - OBJECTIVES: This short commentary examines the factors that led to Food and Drug Administration's approval of the first plant-derived biologic. RESULTS: In 2012, the first plant-derived protein pharmaceutical (biologic) was approved for commercial use in humans. The product, a recombinant form of human beta glucocerebrosidase marketed as ELELYSO, was developed by Protalix Biotherapeutics (Carmiel, Israel). The foresight to select this particular therapeutic product for development, flawless production pipeline, and serendipity seem to provide the key in explaining how ELELYSO became the first plant-derived biologic to achieve approval by Food and Drug Administration. CONCLUSIONS: While the circumstances that enabled Protalix and its scientists to become the first to arrive at this historic milestone are perhaps unique, it is anticipated that more biologics will follow suit in winning regulatory endorsement. PMID- 26149581 TI - HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe. AB - Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection. PMID- 26149582 TI - Relationship between single and multiple perpetrator rape perpetration in South Africa: A comparison of risk factors in a population-based sample. AB - BACKGROUND: Studies of rape of women seldom distinguish between men's participation in acts of single and multiple perpetrator rape. Multiple perpetrator rape (MPR) occurs globally with serious consequences for women. In South Africa it is a cultural practice with defined circumstances in which it commonly occurs. Prevention requires an understanding of whether it is a context specific intensification of single perpetrator rape, or a distinctly different practice of different men. This paper aims to address this question. METHODS: We conducted a cross-sectional household study with a multi-stage, randomly selected sample of 1686 men aged 18-49 who completed a questionnaire administered using an Audio-enhanced Personal Digital Assistant. We attempted to fit an ordered logistic regression model for factors associated with rape perpetration. RESULTS: 27.6 % of men had raped and 8.8 % had perpetrated multiple perpetrator rape (MPR). Thus 31.9 % of men who had ever raped had done so with other perpetrators. An ordered regression model was fitted, showing that the same associated factors, albeit at higher prevalence, are associated with SPR and MPR. CONCLUSIONS: Multiple perpetrator rape appears as an intensified form of single perpetrator rape, rather than a different form of rape. Prevention approaches need to be mainstreamed among young men. PMID- 26149583 TI - Structural Evolution of Chemically-Driven RuO2 Nanowires and 3-Dimensional Design for Photo-Catalytic Applications. AB - Growth mechanism of chemically-driven RuO2 nanowires is explored and used to fabricate three-dimensional RuO2 branched Au-TiO2 nanowire electrodes for the photostable solar water oxidation. For the real time structural evolution during the nanowire growth, the amorphous RuO2 precursors (Ru(OH)3 . H2O) are heated at 180 ( degrees )C, producing the RuO2 nanoparticles with the tetragonal crystallographic structure and Ru enriched amorphous phases, observed through the in-situ synchrotron x-ray diffraction and the high-resolution transmission electron microscope images. Growth then proceeds by Ru diffusion to the nanoparticles, followed by the diffusion to the growing surface of the nanowire in oxygen ambient, supported by the nucleation theory. The RuO2 branched Au-TiO2 nanowire arrays shows a remarkable enhancement in the photocurrent density by approximately 60% and 200%, in the UV-visible and Visible region, respectively, compared with pristine TiO2 nanowires. Furthermore, there is no significant decrease in the device's photoconductance with UV-visible illumination during 1 day, making it possible to produce oxygen gas without the loss of the photoactvity. PMID- 26149584 TI - Injection scheme for intravitreal bevacizumab therapy for macular oedema due to central retinal vein occlusion: results of a multicenter study. PMID- 26149585 TI - The Future of Sublingual Immunotherapy in the United States. AB - Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC). The Food and Drug Administration (FDA) in the USA has approved three SLIT tablets for the treatment of AR and ARC in relation to pollen. Specifically, Grastek(r) and Oralair(r) are two formulations approved to treat patients suffering with AR/ARC to grass pollen, and RagwitekTM is a formulation approved to treat patients suffering with AR/ARC to ragweed pollen. Although these approvals provide support for physicians to prescribe SLIT, barriers to prescribing SLIT still remain such as FDA approval for additional formulations, a standard dose and dosing schedule, and cost/insurance coverage. In order to further support the use of SLIT, research is currently being conducted to expand the indication for SLIT to other common comorbidities to AR/ARC. For example, allergic asthma, food allergies, and atopic dermatitis are other diseases which are being explored. The future of SLIT in the USA is unknown; however, education will be necessary for both providers and patients. PMID- 26149586 TI - Humoral Primary Immunodeficiencies in Chronic Rhinosinusitis. AB - Chronic rhinosinusitis (CRS) may be the primary presenting symptom for primary immunodeficiencies (PID). PID can affect the humoral or the cellular immune system. This paper provides an overview of PID which affect the humoral immune system, with details around the diagnostic criteria, the epidemiology, the subtypes, the clinical manifestations, underlying molecular mechanisms, methods to screen for PID and the management of CRS in the context of PID. A high clinical suspicion of PID is required when assessing patients with CRS who are refractory to maximal medical therapy. PMID- 26149588 TI - Hymenoptera Anaphylaxis and C-kit Mutations: An Unexpected Association. AB - Clinical manifestations of mastocytosis in adults comprise signs and symptoms linked to mast cell (MC) activation, including anaphylaxis. Depending on MC burden, adults can be diagnosed with systemic mastocytosis, when the WHO criteria are fulfilled, or with other clonal MC disorders, characterized by MC mediator symptoms and demonstration of activating KIT mutations and/or expression of CD25 on MCs. There is a specific link between mastocytosis and hymenoptera venom allergy (HVA): the reported frequency of HVA in mastocytosis is 20-50 % and raises to 60-80 % in patients affected by indolent systemic mastocytosis without skin lesions. The presentation of HVA characterized by severe hypotension in the absence of urticarial or angioedema is typical in patient with an underlying MC disorder, even in the presence of normal baseline serum tryptase levels. PMID- 26149587 TI - Regulation of Adaptive Immunity in Health and Disease by Cholesterol Metabolism. AB - Four decades ago, it was observed that stimulation of T cells induces rapid changes in cellular cholesterol that are required before proliferation can commence. Investigators returning to this phenomenon have finally revealed its molecular underpinnings. Cholesterol trafficking and its dysregulation are now also recognized to strongly influence dendritic cell function, T cell polarization, and antibody responses. In this review, the state of the literature is reviewed on how cholesterol and its trafficking regulate the cells of the adaptive immune response and in vivo disease phenotypes of dysregulated adaptive immunity, including allergy, asthma, and autoimmune disease. Emerging evidence supporting a potential role for statins and other lipid-targeted therapies in the treatment of these diseases is presented. Just as vascular biologists have embraced immunity in the pathogenesis and treatment of atherosclerosis, so should basic and clinical immunologists in allergy, pulmonology, and other disciplines seek to encompass a basic understanding of lipid science. PMID- 26149589 TI - Role of Rhinopharyngoscopy in Diagnosis of Rhinopathies. AB - Rhinopathies, or diseases of the sinonasal cavity, are a heterogeneous group of disorders ranging from benign entities to malignant processes. Proper evaluation and treatment of rhinopathies are dependent on accurate visualization and characterization of the disease processes. Prior methods of evaluation of the sinonasal cavity were dependent largely on anterior rhinoscopy, which unfortunately provides poor visualization of the superior, posterior, and lateral extent of the sinonasal cavity. With the advent of high-definition flexible and rigid endoscopes, rhinopharyngoscopy has proven to be a critical component in the evaluation of the sinonasal cavity. Here, we discuss rhinopharyngoscopy with emphasis on technique and evaluation of common rhinopathies and future developments. PMID- 26149591 TI - Design, synthesis and preliminary bioactivity evaluations of substituted quinoline hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors. AB - Inhibition of HDACs activity has become a promising therapeutic strategy in clinical practice to reverse the abnormal epigenetic states of cancer and other diseases. Therefore, HDAC inhibitors become a relatively new class of anti-cancer agent. In the present study, we reported the design and synthesis of a series of novel HDAC inhibitors using various substituted quinoline rings as the cap group. In vitro studies showed that some compounds have good inhibitory activities against HDACs and potent antiproliferative activities in some tumor cell lines. Especially, compound 9w (IC50=85 nM), exhibited better inhibitory effect compared with SAHA (IC50=161 nM). PMID- 26149590 TI - Hypersensitivity to Aspirin and other NSAIDs: Diagnostic Approach in Patients with Chronic Rhinosinusitis. AB - Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) associated with chronic rhinosinusitis (CRS) and/or asthma comprises a distinct clinical syndrome referred to as NSAIDs exacerbated respiratory disease (NERD). Patients with NERD tend to have more severe course of both upper (CRS and nasal polyps) and lower airway (asthma) diseases and are usually recalcitrant to conventional treatment modalities. Diagnosing and phenotyping of patients with NERD are critical for prevention of drug-induced adverse reactions and open novel options for management of underlying chronic airway inflammatory diseases. Diagnosis of NERD is based on detailed clinical history confirmed by challenge with aspirin, but new diagnostic approaches are currently being developed. This review article focuses on the diagnostic approach to a patient with CRS and hypersensitivity to NSAIDs, emphasizing the importance of diagnosis for proper patient's management. PMID- 26149592 TI - Self-assembly processes: general discussion. PMID- 26149593 TI - Trends in the incidence rate of device-associated infections in intensive care units after the establishment of the Korean Nosocomial Infections Surveillance System. AB - BACKGROUND: The effectiveness of continuous nationwide surveillance on healthcare associated infections should be investigated in each country. AIM: To assess the rate of device-associated infections (DAIs) in intensive care units (ICUs) since the establishment of the Korean Nosocomial Infections Surveillance System (KONIS). METHODS: Nationwide data were obtained on the incidence rate of DAI in ICUs reported to KONIS by all participating hospitals. The three major DAIs were studied: ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CABSI), and catheter-associated urinary tract infection (CAUTI). The pooled and year-wise incidence rates (cases per 1000 device-days) of these DAIs were determined for the period 2006 and 2012. In addition, data from institutions that had participated in KONIS for at least three consecutive years were analysed separately. FINDINGS: The number of ICUs participating in KONIS gradually increased from 76 in 2006 to 162 in 2012. Between 2006 and 2012, the incidence rate per 1000 device-days for VAP decreased significantly from 3.48 to 1.64 (F = 11, P < 0.01), for CAUTI the rate decreased non-significantly from 1.85 to 1.26 (F = 2.02, P = 0.07), and for CABSI the rate also decreased non significantly from 3.4 to 2.57 (F = 1.73, P = 0.12). In the 132 ICUs that had participated in KONIS for at least three consecutive years, the VAP rate significantly decreased from the first year to third year (F = 20.57, P < 0.01), but the rates of CAUTI (F = 1.06, P = 0.35) and CABSI (F = 1.39, P = 0.25) did not change significantly. CONCLUSION: The decreased incidence rate of VAP in ICUs in Korea might be associated with the continuous prospective surveillance provided by KONIS. PMID- 26149594 TI - Burden of gastroenteritis outbreaks: specific epidemiology in a cohort of institutions caring for dependent people. AB - BACKGROUND: In institutions caring for dependent people, viral gastroenteritis occurs frequently and is highly contagious. In elderly persons, these episodes can lead to hospitalization and occasionally death. AIM: To study the impact of gastroenteritis outbreaks (GOs) in institutions caring for dependent people. METHODS: This study was conducted on 18 sites consisting of 35 units from four different disciplines (geriatric medicine and rehabilitation, psychogeriatrics, geriatric nursing homes, and specialized care homes for adults with physical and mental disabilities). Spatio-temporal analysis of GOs was performed during six winter seasons, and clinical and viral data were analysed with regard to structural parameters (size of the sites and dining-room organization), virus epidemiology and chronology of the outbreaks and type of activities. RESULTS: A total of 98 outbreaks were recorded in the 35 units. The risk of GO was high even outside national epidemic periods. Viruses were searched for in 86 outbreaks and were identified in 96.5% (83/86) of these outbreaks: norovirus genotype GII.4 (59.0%, 49/83), other viruses (41.0%, 34/83). There were variations between surveillance periods in terms of GO frequencies and attack rates and types of viruses. Dining-room organization could be a factor in cross-infection at a site. CONCLUSION: Specific surveillance that takes into account the precise epidemiology needs to be developed in institutions caring for dependent people in order to improve infectious disease control and information for healthcare workers. PMID- 26149596 TI - An Amorphous Carbon Nitride Photocatalyst with Greatly Extended Visible-Light Responsive Range for Photocatalytic Hydrogen Generation. AB - Amorphous carbon nitride (ACN) with a bandgap of 1.90 eV shows an order of magnitude higher photocatalytic activity in hydrogen evolution under visible light than partially crystalline graphitic carbon nitride with a bandgap of 2.82 eV. ACN is photocatalytically active under visible light at a wavelength beyond 600 nm. PMID- 26149595 TI - Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-kappaB activities. AB - This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-alpha and IL-1beta in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-kappaB p65, IkappaBalpha and IKKbeta stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-kappaB activation through restraining the expression and phosphorylation of the relevant proteins in NF kappaB signal pathway, hindering transcription of NF-kappaB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury. PMID- 26149597 TI - Perspectives on Canadian core fellowship training in pediatric anesthesia: a survey of graduate fellows. AB - BACKGROUND: Educators in anesthesia have an obligation to ensure that fellowship programs are training anesthesiologists to meet the highest standards of performance in clinical and academic practice. The objective of this survey was to characterize the perspectives of graduates of Canadian core fellowship programs in pediatric anesthesia (during a ten-year period starting in 2003) on the adequacies and inadequacies of fellowship training. METHODS: We conducted an electronic survey of graduates from eight departments of pediatric anesthesia in Canada who completed one-year core fellowship training in pediatric anesthesia from 2003 to 2013. A novel survey design was implemented, and the content and structure of the design were tested before distribution. Data were collected on respondents' demographics, details of training and practice settings, perceived self-efficacy in subspecialty practices, research experience, and perspectives on one-year core fellowship training in pediatric anesthesia. Descriptive statistics and 95% confidence intervals were determined. RESULTS: The survey was sent to 132 anesthesiologists who completed core fellowship training in pediatric anesthesia in Canada. Sixty-five (49%) completed and eligible surveys were received. Most of the anesthesiologists surveyed perceived that 12 months of core fellowship training are sufficient to acquire the knowledge and critical skills needed to practice pediatric anesthesia. Subspecialty areas most frequently perceived to require improved training included pediatric cardiac anesthesia, chronic pain medicine, and regional anesthesia. CONCLUSIONS: This survey reports perceived deficiencies in domains of pediatric anesthesia fellowship training. These findings should help guide the future development of core and advanced fellowship training programs in pediatric anesthesia. PMID- 26149598 TI - A prospective observational study comparing a physiological scoring system with time-based discharge criteria in pediatric ambulatory surgical patients. AB - PURPOSE: Discharge criteria based on physiological scoring systems can be used in the postanesthesia care unit (PACU) to fast-track patients after ambulatory surgery; however, studies comparing physiological scoring systems with traditional time-based discharge criteria are lacking. The purpose of this study was to compare PACU discharge readiness times using physiological vs time-based discharge criteria in pediatric ambulatory surgical patients. METHODS: We recorded physiological observations from consecutive American Society of Anesthesiologists physical status I-III patients aged 1-18 yr who were admitted to the PACU after undergoing ambulatory surgery in a tertiary academic pediatric hospital. The physiological score was a combination of the Aldrete and Chung systems. Scores were recorded every 15 min starting upon arrival in the PACU. Patients were considered fit for discharge once they attained a score >=12 (maximum score, 14), provided no score was zero, with the time to achieve a score >=12 defining the criteria-based discharge (CBD) time. Patients were discharged from the PACU when both the CBD and the existing time-based discharge (TBD) criteria were met. The CBD and TBD data were compared using Kaplan-Meier and log rank analysis. RESULTS: Observations from 506 children are presented. Median (interquartile range [IQR]) age was 5.5 [2.8-9.9] yr. Median [IQR] CBD and TBD PACU discharge readiness times were 30 [15-45] min and 60 [45-60] min, respectively. Analysis of Kaplan-Meier curves indicated a significant difference in discharge times using the different criteria (hazard ratio, 5.43; 95% confidence interval, 4.51 to 6.53; P < 0.001). All patients were discharged home without incident. CONCLUSIONS: This prospective study suggests that discharge decisions based on physiological criteria have the potential for significantly speeding the transit of children through the PACU, thereby enhancing PACU efficiency and resource utilization. PMID- 26149599 TI - Epiglottic melanosis. PMID- 26149600 TI - Thoracolumbar interfascial plane (TLIP) block: a pilot study in volunteers. AB - PURPOSE: Regional anesthesia has been shown to improve outcomes in several recent studies. The transversus abdominis plane (TAP) block provides anesthesia to the abdominal wall by introducing local anesthetic to the ventral rami of the thoracolumbar nerves. This work quantifies the area of anesthesia obtained after performing the novel thoracolumbar interfascial plane block (analogous to the TAP block but intended for the back) which targets the sensory component of the dorsal rami of the thoracolumbar nerves. METHODS: Ten participants underwent bilateral ultrasound-guided injections of 0.2% ropivacaine 20 mL into the fascial plane between the multifidus and longissimus muscles. After five and 20 min, respectively, the area of anesthesia was plotted on the participant's back. Anesthesia was defined as loss of point discrimination to pinprick. RESULTS: Participants reported a mean (SD) area of anesthesia surrounding the needle injection site of 137.4 (71.0) cm(2) and 217.0 (84.7) cm(2) at five and 20 min after injection, respectively. The mean (SD) cephalad and caudal spread of local anesthetic from the site of injection was 6.5 (1.8) cm and 3.9 (1.2) cm, respectively. There were no complications or adverse events reported. CONCLUSION: This report shows that a reproducible area of anesthesia can be obtained by ultrasound-guided injection of local anesthetic in the fascial plane between the multifidus and longissimus muscles of the thoracolumbar spine. The area of anesthesia consistently covered the midline and had a predictable spread. This project was registered with clinicaltrials.gov (NCT02297191). PMID- 26149601 TI - Effect of prophylactic benzydamine hydrochloride on postoperative sore throat and hoarseness after tracheal intubation using a double-lumen endobronchial tube: a randomized controlled trial. AB - PURPOSE: We evaluated the prophylactic effect of benzydamine hydrochloride (BH) spray on postoperative sore throat and hoarseness secondary to intubation with a double-lumen endobronchial tube (DLT). METHODS: Ninety-two adult patients undergoing thoracic surgery using DLT intubation were studied. The DLT cuff and oropharyngeal cavity were sprayed with normal saline (Group S; n = 46) or BH (Group BH; n = 46) prior to intubation. Postoperative sore throat and hoarseness were evaluated at one, six, and 24 hr after surgery. Sore throat was evaluated using a 0-100 mm visual analogue scale (VAS). Hoarseness was defined as a change in voice quality. RESULTS: Compared with Group S, postoperative sore throat occurred less frequently in Group BH at one hour (mean difference, 28.3%; 95% confidence interval [CI], 8.7 to 45.1; P = 0.01), at six hours (mean difference, 32.6%; 95% CI, 12.6 to 49.2; P < 0.01), and at 24 hr (mean difference, 28.3%; 95% CI, 9.3 to 44.7; P = 0.01) after surgery. Group BH had lower VAS scores for postoperative sore throat at one hour (mean difference, 12.8; 95% CI, 4.9 to 20.7), at six hours (mean difference, 11.9; 95% CI, 4.8 to 19.1; P < 0.01), and at 24 hr (mean difference, 5.3; 95% CI, 0.9 to 9.7; P = 0.01) after surgery. Hoarseness also occurred less frequently in Group BH at one hour (mean difference, 23.9%; 95% CI, 6.8 to 39.6; P = 0.01), at six hours (mean difference, 23.9%; 95% CI, 7.4 to 39.3; P = 0.01), and at 24 hr (mean difference, 21.7%; 95% CI, 5.5 to 37.0; P = 0.02) after surgery (P < 0.01). CONCLUSIONS: Prophylactic application of BH to the DLT cuff and oropharyngeal cavity reduces the incidence and severity of postoperative sore throat and the incidence of hoarseness associated with DLT intubation. The trial was registered at the Clinical Research Information Service (KCT0001068). PMID- 26149602 TI - Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis. AB - BACKGROUND: Reports have demonstrated the superior activity of combining both irinotecan and oxaliplatin (FOLFOXIRI) therapy. An option for gaining similar benefits with less toxicity would be the administration of irinotecan through a hepatic artery approach. The aim of this study was to assess the response and adverse event rates for irinotecan drug-eluting beads (DEBIRI) with folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab as a first-line treatment for unresectable colorectal liver metastasis. METHODS: Patients with colorectal liver metastases were randomly assigned to modified FOLFOX (mFOLFOX) and bevacizumab or mFOLFOX6, bevacizumab, and DEBIRI (FOLFOX-DEBIRI). The primary endpoint was the response rate. The secondary endpoints were adverse events, the rate of conversion to resection, and progression-free survival. RESULTS: The intention-to-treat population comprised 70 patients: 10 patients in the pilot and then 30 patients randomly assigned to the FOLFOX-DEBIRI arm and 30 patients randomly assigned to the FOLFOX/bevacizumab arm. The 2 groups were similar with respect to the extent of liver involvement (30% vs 30%), but a greater percentage of patients in the FOLFOX-DEBIRI arm had an Eastern Cooperative Oncology Group performance status of 1 or 2 (57% vs 31%) and extrahepatic disease (56% vs 32%, P = .02). The median numbers of chemotherapy cycles were similar (10 vs 9), and there were similar rates of grade 3/4 adverse events (54% for the FOLFOX-DEBIRI group vs 46% for the FOLFOX/bevacizumab group). The overall response rate was significantly greater in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm at 2 (78% vs 54%, P = .02), 4 (95% vs 70%, P = .03), and 6 months (76% vs 60%, P = .05). There was significantly more downsizing to resection in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm (35% vs 16%, P = .05), and there was improved median progression-free survival (15.3 vs 7.6 months). CONCLUSIONS: The simultaneous administration of mFOLFOX6 (with or without bevacizumab) and DEBIRI through the hepatic artery (FOLFOX-DEBIRI) is safe and does not cause treatment delays or increase the systemic toxicity of chemotherapy. This strategy leads to improved overall response rates, improved hepatic progression-free survival, and more durable overall progression-free survival in patients downsized to resection. PMID- 26149603 TI - Metabonomic analysis of potential biomarkers and drug targets involved in diabetic nephropathy mice. AB - Diabetic nephropathy (DN) is one of the lethal manifestations of diabetic systemic microvascular disease. Elucidation of characteristic metabolic alterations during diabetic progression is critical to understand its pathogenesis and identify potential biomarkers and drug targets involved in the disease. In this study, (1)H nuclear magnetic resonance ((1)H NMR)-based metabonomics with correlative analysis was performed to study the characteristic metabolites, as well as the related pathways in urine and kidney samples of db/db diabetic mice, compared with age-matched wildtype mice. The time trajectory plot of db/db mice revealed alterations, in an age-dependent manner, in urinary metabolic profiles along with progression of renal damage and dysfunction. Age dependent and correlated metabolite analysis identified that cis-aconitate and allantoin could serve as biomarkers for the diagnosis of DN. Further correlative analysis revealed that the enzymes dimethylarginine dimethylaminohydrolase (DDAH), guanosine triphosphate cyclohydrolase I (GTPCH I), and 3-hydroxy-3 methylglutaryl-CoA lyase (HMG-CoA lyase) were involved in dimethylamine metabolism, ketogenesis and GTP metabolism pathways, respectively, and could be potential therapeutic targets for DN. Our results highlight that metabonomic analysis can be used as a tool to identify potential biomarkers and novel therapeutic targets to gain a better understanding of the mechanisms underlying the initiation and progression of diseases. PMID- 26149604 TI - Variation in psychosocial influences according to the dimensions and content of children's unusual experiences: potential routes for the development of targeted interventions. AB - The psychosocial processes implicated in the development and maintenance of psychosis differ according to both the dimensional attributes (conviction, frequency, associated distress, adverse life impact) and the content or type (e.g. grandiosity, hallucinations, paranoia) of the psychotic symptoms experienced. This has informed the development of 'targeted' cognitive behavioural therapy for psychosis (CBTp): interventions focusing on specific psychological processes in the context of particular symptom presentations. In adults, larger effect sizes for change in primary outcomes are typically reported in trials of targeted interventions, compared to those for trials of generic CBTp approaches with multiple therapeutic foci. We set out to test the theoretical basis for developing targeted CBTp interventions for young people with distressing psychotic-like, or unusual, experiences (UEs). We investigated variations in the psychosocial processes previously associated with self-reported UE severity (reasoning, negative life events, emotional problems) according to UE dimensional attributes and content/type (using an established five-factor model) in a clinically referred sample of 72 young people aged 8-14 years. Regression analyses revealed associations of conviction and grandiosity with reasoning; of frequency, and hallucinations and paranoia, with negative life events; and of distress/adverse life impact, and paranoia and hallucinations, with emotional problems. We conclude that psychological targets for intervention differ according to particular characteristics of childhood UEs in much the same way as for psychotic symptoms in adults. The development of targeted interventions is therefore indicated, and tailoring therapy according to presentation should further improve clinical outcomes for these young people. PMID- 26149606 TI - Cues indicating location in pigeon navigation. AB - Domesticated Rock Pigeons (Columba livia f. domestica) have been selected for returning home after being displaced. They appear to use many of the physical cue sources available in the natural environment for Map-and-Compass navigation. Two compass mechanisms that have been well documented in pigeons are a time compensated sun compass and a magnetic inclination compass. Location-finding, or map, mechanisms have been more elusive. Visual landmarks, magnetic fields, odors, gravity and now also infrasound have been proposed as sources of information on location. Even in highly familiar locations, pigeons appear to neither use nor need landmarks and can even return to the loft while wearing frosted lenses. Direct and indirect evidence indicates magnetic field information influences pigeon navigation in ways that are consistent with magnetic map components. The role of odors is unclear; it might be motivational in nature rather than navigational. The influence of gravity must be further analyzed. Experiments with infrasound have been interpreted in the sense that they provide information on the home direction, but this hypothesis is inconsistent with the Map-and-Compass Model. All these factors appear to be components of a multifactorial system, with the pigeons being opportunistic, preferring those cues that prove most suitable in their home region. This has made understanding the roles of individual cues challenging. PMID- 26149607 TI - Back to the future: using historical climate variation to project near-term shifts in habitat suitable for coast redwood. AB - Studies that model the effect of climate change on terrestrial ecosystems often use climate projections from downscaled global climate models (GCMs). These simulations are generally too coarse to capture patterns of fine-scale climate variation, such as the sharp coastal energy and moisture gradients associated with wind-driven upwelling of cold water. Coastal upwelling may limit future increases in coastal temperatures, compromising GCMs' ability to provide realistic scenarios of future climate in these coastal ecosystems. Taking advantage of naturally occurring variability in the high-resolution historic climatic record, we developed multiple fine-scale scenarios of California climate that maintain coherent relationships between regional climate and coastal upwelling. We compared these scenarios against coarse resolution GCM projections at a regional scale to evaluate their temporal equivalency. We used these historically based scenarios to estimate potential suitable habitat for coast redwood (Sequoia sempervirens D. Don) under 'normal' combinations of temperature and precipitation, and under anomalous combinations representative of potential future climates. We found that a scenario of warmer temperature with historically normal precipitation is equivalent to climate projected by GCMs for California by 2020-2030 and that under these conditions, climatically suitable habitat for coast redwood significantly contracts at the southern end of its current range. Our results suggest that historical climate data provide a high-resolution alternative to downscaled GCM outputs for near-term ecological forecasts. This method may be particularly useful in other regions where local climate is strongly influenced by ocean-atmosphere dynamics that are not represented by coarse-scale GCMs. PMID- 26149605 TI - Facial emotion perception by intensity in children and adolescents with 22q11.2 deletion syndrome. AB - Difficulties in the recognition of emotions in expressive faces have been reported in people with 22q11.2 deletion syndrome (22q11.2DS). However, while low intensity expressive faces are frequent in everyday life, nothing is known about their ability to perceive facial emotions depending on the intensity of expression. Through a visual matching task, children and adolescents with 22q11.2DS as well as gender- and age-matched healthy participants were asked to categorise the emotion of a target face among six possible expressions. Static pictures of morphs between neutrality and expressions were used to parametrically manipulate the intensity of the target face. In comparison to healthy controls, results showed higher perception thresholds (i.e. a more intense expression is needed to perceive the emotion) and lower accuracy for the most expressive faces indicating reduced categorisation abilities in the 22q11.2DS group. The number of intrusions (i.e. each time an emotion is perceived as another one) and a more gradual perception performance indicated smooth boundaries between emotional categories. Correlational analyses with neuropsychological and clinical measures suggested that reduced visual skills may be associated with impaired categorisation of facial emotions. Overall, the present study indicates greater difficulties for children and adolescents with 22q11.2DS to perceive an emotion in low-intensity expressive faces. This disability is subtended by emotional categories that are not sharply organised. It also suggests that these difficulties may be associated with impaired visual cognition, a hallmark of the cognitive deficits observed in the syndrome. These data yield promising tracks for future experimental and clinical investigations. PMID- 26149608 TI - Patterns of mandible fracture in children under 12 years in a district trauma center in India. AB - AIM: This study aims to present the data of mandibular fracture among children in the age group of 0-12 years treated in a district trauma center in India. STUDY DESIGN: Sixty-two children younger than 12 years treated for mandibular fractures over two-and-a-half-year period were studied by age, gender, anatomic site, etiology, socioeconomic status, residing area, interval from trauma to reporting, and treatment performed. The cases were divided into three age groups, and the records of the patients were analyzed. RESULTS: The male to female ratio was 1.58:1. Common fall and fall from bike together was a cause for injury in 50% (31 patients), of total patients. Condylar fractures occurred in 25 patients (40.3%). Multiple fractures were seen in 13% of the patients. In 47 (75.8%) patients, associated injuries other than the mandibular fractures were also present. Most patients with mandibular fractures were treated by closed reduction (36 patients, 58%). Conservative treatment and open reduction were done in 18 (29%) and 8 (13%) patients, respectively. CONCLUSION: In addition to factors such as age, gender, etiology, anatomic site, and treatment of mandibular fracture, this study also reported statistics regarding other factors such as residing area, socioeconomic status, and interval from trauma to reporting in Indian patients. It is hoped that the data presented here will be valuable to the government agencies and healthcare professionals for planning treatment, recommending preventive measures and encouraging research in this area. PMID- 26149609 TI - Functional MRI of visual responses in the awake, behaving marmoset. AB - The visual brain is composed of interconnected subcortical and cortical structures that receive and process image information originating in the retina. The visual system of nonhuman primates, in particular macaques, has been studied in great detail in order to elucidate principles of human sensation and perception. The common marmoset (Callithrix jacchus) is a small New World monkey of growing interest as a primate model for neuroscience. Marmosets have advantages over macaques because of their small size, lissencephalic cortex, and growing potential for viral and genetic manipulations. Previous anatomical studies and electrophysiological recordings in anesthetized marmosets have shown that this species' cortical visual hierarchy closely resembles that of other primates, including humans. Until now, however, there have been no attempts to systematically study visual responses throughout the marmoset brain using fMRI. Here we show that awake marmosets readily learn to carry out a simple visual task inside the bore of an MRI scanner during functional mapping experiments. Functional scanning at 500 MUm in-plane resolution in a 30 cm horizontal bore at 7 T revealed robust positive blood oxygenation level-dependent (BOLD) fMRI responses to visual stimuli throughout visual cortex and associated subcortical areas. Nonvisual sensory areas showed negative contrasts to visual stimuli compared to the fixation dot only baseline. Structured images of objects and faces led to stronger responses than scrambled control images at stages beyond early visual cortex. Our study establishes fMRI mapping of visual responses in awake, behaving marmosets as a straightforward and valuable tool for assessing the functional organization of the primate brain at high resolution. PMID- 26149612 TI - Diabetes: DNA methylation affects T2DM risk. PMID- 26149610 TI - Controllability modulates the neural response to predictable but not unpredictable threat in humans. AB - Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress. PMID- 26149611 TI - Differential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on nicotine versus cocaine self-administration and relapse in squirrel monkeys. AB - RATIONALE: Group II metabotropic glutamate receptors (mGluR2 and mGluR3) have been suggested to play an important role in mediation of drug-reinforced behaviors, as well as in the mechanisms underlying relapse in abstinent subjects. The prototypical mGluR2/3 agonist, LY379268, has been shown to attenuate nicotine reinforcement and cue-induced reinstatement of drug seeking in rats, as well as reinstatement induced by drug-associated stimuli and contexts across different drugs of abuse (i.e., cocaine, heroin, and methamphetamine). However, in primates, LY379268 has been shown to produce conflicting results on abuse-related effects of cocaine, and there are no data available for nicotine. OBJECTIVES: To explore the therapeutic potential of mGluR2/3 agonists, we compared the effects of LY379268 (0.03-1.0 mg/kg) on nicotine, cocaine, and food self-administration under a fixed-ratio (FR10) schedule in three separate groups of squirrel monkeys. Moreover, we studied the effects of LY379268 on nicotine/cocaine priming-induced and cue-induced reinstatement of drug-seeking behavior in nicotine- and cocaine experienced groups of animals. RESULTS: LY379268 blocked nicotine, but not cocaine, self-administration in monkeys. There was a partial overlap between doses that affected nicotine and food self-administration. In abstinent monkeys, LY379268 dose-dependently blocked nicotine, but not cocaine, priming-induced reinstatement of drug seeking. In both cocaine-experienced and nicotine experienced groups of animals, LY379268 potently reduced cue-induced reinstatement of drug-seeking behavior. CONCLUSIONS: The present findings provide strong support for the potential utility of mGlu2/3 receptor agonists for the treatment of nicotine dependence and suggest their utility for prevention of relapse induced by environmental cues associated with drug taking. PMID- 26149613 TI - Reproductive endocrinology: Are intramuscular testosterone injections harmful? PMID- 26149614 TI - Lipids: Xenograft model of lipid metabolism. PMID- 26149615 TI - Thyroid hormone transporters--functions and clinical implications. PMID- 26149616 TI - Pregnancy: Fetal signalling initiates parturition. PMID- 26149617 TI - Development and Validation of a Pain Behavior Assessment in Patients with Chronic Low Back Pain. AB - PURPOSE: High levels of pain behavior adversely affect the success of multidisciplinary rehabilitation of patients with chronic nonspecific low back pain (CNSLBP). Functional capacity evaluation (FCE) assessment should detect high levels of pain behavior to prevent the inclusion of unsuitable patients to functional rehabilitation programs. The aim of this study was to develop a Pain Behavior Assessment (PBA) and to evaluate its construct validity. METHODS: The PBA was developed by experts in the field and is literature-based. Inclusion criteria for participants of the validation study were: CNSLBP, age 20-60 years, referral for fitness-for-work evaluation. The PBA was applied by physiotherapists during FCE. Rasch analysis was performed to evaluate the construct validity of the PBA. Internal consistency was indicated by the person separation index (PSI), which corresponds to Cronbach's alpha. RESULTS: 145 male (72.5%) and 55 female patients were included. Rasch analysis removed 11 items due to misfit and redundancy, resulting in a final PBA of 41 items. Item mean fit residual was 0.33 (SD 1.06) and total item Chi square 100.39 (df = 82, p = 0.08). The PSI value was 0.83. DIF analysis for age and gender revealed no bias. CONCLUSIONS: The PBA is a valid assessment tool to describe pain behavior in CNSLBP patients. The high PSI-value justifies the use of the PBA in individuals. The PBA may help to screen patients for high levels of pain behavior. PMID- 26149618 TI - Using Cartoons to Transfer Knowledge Concerning the Principles of Work Disability Prevention Among Stakeholders. AB - Purpose This study assesses how well two cartoons transfer knowledge of principles of work disability prevention among stakeholders, according to their level of experience. We also document stakeholders' perceptions of the usefulness of the cartoons. Method We performed a descriptive study. Two groups of stakeholders were recruited: (1) experienced (working for more than 2 years in work disability), (2) non-experienced (in training). A self-administered questionnaire with open-ended questions documented stakeholders' understanding of each cartoon box and their perception of the possible usefulness of the cartoons. We transformed qualitative responses into quantitative responses for descriptive purposes. We performed independent t tests to compare the groups' level of understanding, and content analysis for the perception of usefulness. Results Overall, 149 stakeholders (50 experienced and 99 non-experienced) participated and identified 79.4 and 61.4 % of all principles presented in each of the two cartoons respectively. Experienced stakeholders identified more principles compared to non-experienced stakeholders (p = 0.007). Both cartoons were perceived to be useful for knowledge transfer. Conclusions Principles were generally well identified in the cartoons by all participants. Cartoons can be used as an effective tool among stakeholders to achieve a common understanding in order to coordinate their actions. PMID- 26149619 TI - Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine. AB - Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissolution characteristics of the API. Therefore, a BCS biowaiver-based approval of nifedipine containing IR oral dosage forms cannot be recommended for reformulated/new multisource drug products or for major scale-up and postapproval changes to the existing drug products. PMID- 26149620 TI - Temporally tunable, enzymatically responsive delivery of proangiogenic peptides from poly(ethylene glycol) hydrogels. AB - Proangiogenic drugs hold great potential to promote reperfusion of ischemic tissues and in tissue engineering applications, but efficacy is limited by poor targeting and short half-lives. Methods to control release duration or provide enzymatically responsive drug delivery have independently improved drug efficacy. However, no material has been developed to temporally control the rate of enzymatically responsive drug release. To address this void, hydrogels are developed to provide sustained, tunable release of Qk, a proangiogenic peptide mimic of vascular endothelial growth factor, via tissue-specific enzymatic activity. After confirmation that sustained delivery of Qk is necessary for proangiogenic effects, a variety of previously identified matrix metalloproteinase (MMP)-degradable linkers are used to tether Qk to hydrogels. Of these, three (IPES?LRAG, GPQG?IWGQ, and VPLS?LYSG) show MMP-responsive peptide release. These linkers provide tunable Qk release kinetics, with rates ranging from 1.64 to 19.9 * 10(-3) h(-1) in vitro and 4.82 to 8.94 * 10(-3) h(-1) in vivo. While Qk is confirmed to be bioactive as released, hydrogels releasing Qk fail to induce significant vascularization in vivo after one week, likely due to the use of nonenzymatically degradable hydrogels. While Qk is the focus of this study, the approach could easily be adapted to control the delivery of a variety of therapeutic molecules. PMID- 26149621 TI - Frequency and prognostic value of cutaneous molecular residual disease in mycosis fungoides: a prospective multicentre trial of the Cutaneous Lymphoma French Study Group. AB - BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-gamma gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61.8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46.6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50.5%) still being followed up were in CR and 44 of 109 (40.4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1.0; positive predictive value 36.4%; negative predictive value 67.6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years. PMID- 26149622 TI - Surface Grafting via Photo-Induced Copper-Mediated Radical Polymerization at Extremely Low Catalyst Concentrations. AB - Surface-initiated photo-induced copper-mediated radical polymerization is employed to graft a wide range of polyacrylate brushes from silicon substrates at extremely low catalyst concentrations. This is the first time that the controlled nature of the reported process is demonstrated via block copolymer formation and re-initiation experiments. In addition to unmatched copper catalyst concentrations in the range of few ppb, film thicknesses up to almost 1 MUm are achieved within only 1 h. PMID- 26149624 TI - A global network-based protocol for functional inference of hypothetical proteins in Synechocystis sp. PCC 6803. AB - Functional inference of hypothetical proteins (HPs) is a significant task in the post-genomic era. We described here a network-based protocol for functional inference of HPs using experimental transcriptomic, proteomic, and protein protein interaction (PPI) datasets. The protocol includes two steps: i) co expression networks were constructed using large proteomic or transcriptomic datasets of Synechocystis sp. PCC 6803 under various stress conditions, and then combined with a Synechocystis PPI network to generate bi-colored networks that include both annotated proteins and HPs; ii) a global algorithm was adapted to the bi-colored networks for functional inference of HPs. The algorithm ranked the associations between genes/proteins with known GO functional categories, and assumed that the top one ranked HP for each GO functional category might have a function related to the GO functional category. We applied the protocol to all HPs of the model cyanobacterium Synechocystis, and were able to assign putative functions to 122 HPs that have never been functionally characterized previously. Finally, the functional inference was validated by the known biological information of operon, and results showed that more than 70% HPs could be correctly validated. The study provided a new protocol to integrate different types of OMICS datasets for functional inference of HPs, and could be useful in achieving new insights into the Synechocystis metabolism. PMID- 26149623 TI - Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Approach for Discovering Natural Products from Cyanobacteria. AB - An innovative approach was developed for the discovery of new natural products by combining mass spectrometric metabolic profiling with genomic analysis and resulted in the discovery of the columbamides, a new class of di- and trichlorinated acyl amides with cannabinomimetic activity. Three species of cultured marine cyanobacteria, Moorea producens 3L, Moorea producens JHB, and Moorea bouillonii PNG, were subjected to genome sequencing and analysis for their recognizable biosynthetic pathways, and this information was then compared with their respective metabolomes as detected by MS profiling. By genome analysis, a presumed regulatory domain was identified upstream of several previously described biosynthetic gene clusters in two of these cyanobacteria, M. producens 3L and M. producens JHB. A similar regulatory domain was identified in the M. bouillonii PNG genome, and a corresponding downstream biosynthetic gene cluster was located and carefully analyzed. Subsequently, MS-based molecular networking identified a series of candidate products, and these were isolated and their structures rigorously established. On the basis of their distinctive acyl amide structure, the most prevalent metabolite was evaluated for cannabinomimetic properties and found to be moderate affinity ligands for CB1. PMID- 26149625 TI - A selective medium for the isolation of Microbacterium species in oral cavities. AB - The genus Microbacterium has been isolated from the environment, dairy goods, and human clinical specimens. Although, in our previous studies, some Microbacterium species were infrequently detected in oral samples collected from humans, there is currently no report that these organisms, which are capable of causing serious systemic infections, were isolated from the human oral cavity. The aim of the present study was to develop a selective medium to isolate the representative Microbacterium species most frequently detected in human clinical specimens, and reveal the distribution of individual Microbacterium species in the oral cavity. The growth recoveries of representative Microbacterium species on the selective medium, designated as MSM, were sufficient. Moreover, the growth of other representative oral bacteria was markedly inhibited on the selective medium. The proportion of Microbacterium species in the saliva samples of 60 subjects, 20 of whom were removable denture wearers, was then examined. The proportion of these organisms was also examined in environmental samples obtained by swabbing 20 washstands. PCR primers were designed for representative Microbacterium species. The genus Microbacterium was detected in 45% of the saliva and denture plaque samples collected from the twenty removable denture wearers, but was absent in the saliva of the forty non-denture wearers. On the other hand, these organisms were detected in all environmental samples. The genus Microbacterium accounted for 0.00003%, 0.0001%, and 12.6% of the total cultivable bacteria number on the BHI medium in the saliva and denture plaque samples of removable denture wearers and in the environmental samples, respectively. The most predominant Microbacterium species in all positive samples was Microbacterium oxydans. These results indicated that the genus Microbacterium was not a part of the normal flora in the human oral cavity, except for subjects wearing dentures that were contaminated by the environment, and the selective medium, designated as MSM, was useful for isolating Microbacterium species, which are frequently encountered in human clinical specimens, from the various samples. PMID- 26149626 TI - Expeditious screening of candidate proteins for microbial vaccines. AB - Advancements in high-throughput "omics" technologies have revolutionized the way vaccine candidates are identified. Now every surface expressed protein that an organism produces can be identified in silico and possibly made available for the rapid development of recombinant/subunit vaccines. However, evaluating the antigenicity of a large number of candidate proteins is an immense challenge, typically requiring cloning of several hundred candidates followed by immunogenicity screening. Here we report the development of a rapid, high throughput method for screening candidate proteins for vaccines. This method involves utilizing a coupled, cell-free transcription-translation system to screen tagged proteins that are captured at the C-termini using appropriate ligand coated wells in 96 well ELISA plates. The template DNA for the cell-free expression is generated by two sequential PCRs and includes gene coding sequences, promoter, terminator, other necessary cis-acting elements and appropriate tag sequences. The process generates expressible candidate proteins containing two different peptide tags at the N- and the C-termini of the protein molecules. Proteins are screened in parallel for their quantity and immunoreactivity with N-terminal tag antibodies and antisera raised against the pathogen of interest, respectively. Normalization against the total detectable bound protein in the control wells allows for the identification of highly immunoreactive candidates. For this study we selected 30 representatives of >300 potential candidate proteins from Mannheimia haemolytica, a bacterial agent of pneumonia in feedlot cattle for expression with N-terminal Strep-II and C terminal His(x6)-tag and evaluated their relative immunoreactivities using Strep tactin-HRP and rabbit antisera generated against M. haemolytica. Using this system we were able to swiftly and quantitatively analyze and rank the suitability of proteins to identify potentially viable vaccine candidates, with the majority of the high ranking candidates being associated with virulence and pathogenicity. The system is adaptable to any bacterial target and presents an alternative to conventional laborious cloning, expression and screening procedures. PMID- 26149627 TI - Atrial flutter and thromboembolic risk: a systematic review. AB - Atrial flutter confers a thromboembolic risk, but contrary to atrial fibrillation the relationship has only been addressed in few studies. This study performs an up to date systematic review of the literature to investigate the association between atrial flutter and thromboembolic events. Articles were found by MEDLINE, EMBASE search and a manual search of references list in included articles. International guidelines, meta-analyses, reviews, case reports, studies reporting thromboembolic events in relation to ablation, or cardioversion procedures, echocardiography, and observational studies were found eligible in this review. A total of 52 articles were included in this review. During cardioversion, thromboembolic event rates varied from 0% to 6% with a follow-up from 1 week to 6 years. Echocardiographic studies reported prevalence of thrombus material from 0% to 38% and a prevalence of spontaneous echo contrast (SEC) from 21% to 28%. One ablation study in non-anticoagulated patients reported thromboembolic events at 13.9%. Observational studies reported an overall elevated stroke risk (risk ratio 1.4, 95% CI 1.35 to 1.46) and mortality risk (HR 1.9, 95% CI 1.2 to 3.1) with long time follow-up compared with a control group in both studies. Given the limitations and heterogeneity of the data, a meta-analysis was not a part of this systematic review. Notwithstanding the limitations of observational studies and indirect data from echocardiographic studies, this systematic review confirms that clinical thromboembolic events, left atrial thrombus and SEC are highly prevalent in atrial flutter. PMID- 26149628 TI - Positive contrast high-resolution 3D-cine imaging of the cardiovascular system in small animals using a UTE sequence and iron nanoparticles at 4.7, 7 and 9.4 T. AB - BACKGROUND: To show that 3D sequences with ultra-short echo times (UTEs) can generate a positive contrast whatever the magnetic field (4.7, 7 or 9.4 T) and whatever Ultra Small Particles of Iron Oxide (USPIO) concentration injected and to use it for 3D time-resolved imaging of the murine cardiovascular system with high spatial and temporal resolutions. METHODS: Three different concentrations (50, 200 and 500 MUmol Fe/kg) of USPIO were injected in mice and static images of the middle part of the animals were acquired at 4.7, 7 and 9.4 T pre and post contrast with UTE (TE/TR = 0.05/4.5 ms) sequences. Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR) of blood and static tissus were evaluated before and after contrast agent injection. 3D-cine images (TE/TR = 0.05/3.5 ms, scan time < 12 min) at 156 MUm isotropic resolution of the mouse cardiopulmonary system were acquired prospectively with the UTE sequence for the three magnetic fields and with an USPIO dose of 200 MUmol Fe/kg. SNR, CNR and signal homogeneity of blood were measured. High spatial (104 MUm) or temporal (3.5 ms) resolution 3D cine imaging (scan time < 35 min) isotropic resolution were also performed at 7 T with a new sequence encoding scheme. RESULTS: UTE imaging generated positive contrast and higher SNR and CNR whatever the magnetic field and the USPIO concentration used compared to pre-contrast images. Time-resolved 3D acquisition enables high blood SNR (66.6 +/- 4.5 at 7 T) and CNR (33.2 +/- 4.2 at 7 T) without flow or motion artefact. Coronary arteries and aortic valve were visible on images acquired at 104 MUm resolution. CONCLUSIONS: We have demonstrated that by combining the injection of iron nanoparticles with 3D-cine UTE sequences, it was possible to generate a strong positive contrast between blood and surrounding tissues. These properties were exploited to produce images of the cardiovascular system in small animals at high magnetic fields with a high spatial and temporal resolution. This approach might be useful to measure the functional cardiac parameters or to assess anatomical modifications to the blood vessels in cardio vascular disease models. PMID- 26149629 TI - Pharmacotherapy options for labor induction. AB - INTRODUCTION: Induction of labor remains one of the most commonly performed procedures in the US and in other developed countries around the world. Various agents for cervical ripening are used prior to induction; the most commonly used are prostaglandins and oxytocin. The ideal agent is one that decreases time to vaginal delivery without compromising maternal and/or fetal safety. AREAS COVERED: This article reviews the current pharmacologic methods available for induction of labor. Although these agents have been extensively studied and their safety and efficacy profile are well accepted, there is still ongoing research to determine the safest and most effective method. The article discusses the impact of pharmacogenomics as it relates to the most common induction agents. The dosing, route of administration, and side effects of these agents are reviewed. EXPERT OPINION: Prostaglandins and oxytocin have been proven to be safe and effective methods of induction. However, the optimal medication for induction is yet to be determined. Although there are currently no pharmacogenomic findings that affect dosing of either prostaglandins or oxytocin, this is a growing area of research. In the near future, it may become clear that there is no 'one regimen for all' when selecting an induction or cervical ripening agent, or any other pharmaceutical altogether. PMID- 26149630 TI - Future of clinical EEG in psychiatric disorders: Shifting the focus from diagnosis to the choice of optimal treatment. PMID- 26149631 TI - High frequency repetitive sensory stimulation improves temporal discrimination in healthy subjects. AB - OBJECTIVE: High frequency electrical stimulation of an area of skin on a finger improves two-point spatial discrimination in the stimulated area, likely depending on plastic changes in the somatosensory cortex. However, it is unknown whether improvement also applies to temporal discrimination. METHODS: Twelve young and ten elderly volunteers underwent the stimulation protocol onto the palmar skin of the right index finger. Somatosensory temporal discrimination threshold (STDT) was evaluated before and immediately after stimulation as well as 2.5h and 24h later. RESULTS: There was a significant reduction in somatosensory temporal threshold only on the stimulated finger. The effect was reversible, with STDT returning to the baseline values within 24h, and was smaller in the elderly than in the young participants. CONCLUSIONS: High frequency stimulation of the skin focally improves temporal discrimination in the area of stimulation. Given previous suggestions that the perceptual effects rely on plastic changes in the somatosensory cortex, our results are consistent with the idea that the timing of sensory stimuli is, at least partially, encoded in the primary somatosensory cortex. SIGNIFICANCE: Such a protocol could potentially be used as a therapeutic intervention to ameliorate physiological decline in the elderly or in other disorders of sensorimotor integration. PMID- 26149633 TI - Mechanism of immobilized protein A binding to immunoglobulin G on nanosensor array surfaces. AB - Protein A is often used for the purification and detection of antibodies such as immunoglobulin G (IgG) because of its quadrivalent domains that bind to the Fc region of these macromolecules. However, the kinetics and thermodynamics of the binding to many sensor surfaces have eluded mechanistic description due to complexities associated with multivalent interactions. In this work, we use a near-infrared (nIR) fluorescent single-walled carbon nanotube sensor array to obtain the kinetics of IgG binding to protein A, immobilized using a chelated Cu(2+)/His-tag chemistry to hydrogel dispersed sensors. A bivalent binding mechanism is able to describe the concentration dependence of the effective dissociation constant, KD,eff, which varies from 100 pM to 1 MUM for IgG concentrations from 1 ng mL(-1) to 100 MUg mL(-1), respectively. The mechanism is shown to describe the unusual concentration-dependent scaling demonstrated by other sensor platforms in the literature as well, and a comparison is made between resulting parameters. For comparison, we contrast IgG binding with that of human growth hormone (hGH) to its receptor (hGH-R) which displays an invariant dissociation constant at KD = 9 MUM. These results should aid in the use of protein A and other recognition elements in a variety of sensor types. PMID- 26149634 TI - [Comparative clinical study of 2 surgical techniques for trapeziometacarpal osteoarthritis]. AB - OBJECTIVE: In trapeziometacarpal osteoarthritis (or rhizarthrosis), there is great controversy over the surgical technique to choose: simple trapeziectomy, resection-interposition arthroplasty, interposition arthroplasty suspension-or arthroplasty with implant or prosthesis. These latter 2 are the most used without consensus in the literature on the technique to choose and without sufficient comparative studies. The objective is to compare the 2 techniques most used today: suspension-interposition arthroplasty and arthroplasty with prosthesis. MATERIAL AND METHOD: A prospective study was conducted on 15 patients diagnosed with grade 2-3 rhizarthrosis treated with interposition arthroplasty-suspension (group 1) and 15 with prosthesis (group 2) showing clinical outcomes, advantages and disadvantages of each. The study variables were the visual analogue scale (VAS), the DASH questionnaire, the grip strength, the strength of end to end and end-lateral clamp, the joint balance adduction-abduction and preemption retropositioning, and the opposition. The 2 groups are from 2 different hospitals operated on by a hand surgeon from the Hand Unit. The follow-up time for all patients included in the study was 12 months. RESULTS: The VAS, DASH and grip strength at 12 months did not show significant differences. As regards the strength of end to end and end-lateral clamp, group 2 showed the highest values in all follow-up periods with statistically significant differences. CONCLUSIONS: Patient selection and surgical experience is essential, given the satisfactory results of both techniques. Arthroplasty prosthesis is reserved for grades 2 and 3, middle-aged patients, good trapezium architecture, and experienced surgeons. PMID- 26149635 TI - Visceral adiposity index, hypertriglyceridemic waist phenotype and chronic kidney disease in a southern Chinese population: a cross-sectional study. AB - OBJECTIVE: To explore the relationships between visceral adiposity index (VAI), hypertriglyceridemic waist phenotype (HW phenotype) and chronic kidney disease (CKD). METHODS: A cross-sectional study was conducted in Zhuhai City June-October 2012. A total of 2142 participants were recruited. Logistic regression was used to evaluate the associations between VAI, HW phenotype and CKD. RESULTS: After adjustment for age, VAI was significantly associated with CKD (OR 2.16, 95 % CI 1.25-3.74, P = 0.006) in women. Further adjusted for potential confounders, the association was still significant in women (OR 2.07, 95 % CI 1.17-3.64, P = 0.01). However, the association was abolished when adding diabetes and hypertension to the model (OR 1.68, 95 % CI 0.92-3.06, P = 0.09). The age adjusted OR (95 % CI, P) of CKD associated with HW phenotype was 2.21 (1.29-3.76, 0.004) and 2.54 (1.53-4.22, <0.001) for men and women, respectively. Further adjusted for potential confounders, the associations were still significant in both subgroups. The OR for CKD was 2.41 (95 % CI 1.42-4.12, P = 0.001) and 2.32 (95 % CI 1.31-4.11, P = 0.004) for women and men, respectively. When further adjusted for diabetes and hypertension, the association of HW phenotype and CKD was significant (OR 1.88, 95 % CI 1.05-3.36, P = 0.033) in women. However, the model is abolished in men (OR 1.50, 95 % CI 0.81-2.78, P = 0.19). CONCLUSION: Our results suggest that both VAI and the HW phenotype might be useful clinical indicators of CKD in China for females but not for males. The HW phenotype associated more strongly with CKD, compared with VAI. PMID- 26149636 TI - Nocturnal enuresis with spina bifida occulta: Does it interfere behavioral management success? AB - PURPOSE: We aimed to investigate the incidence of spina bifida occulta (SBO) in patients with nocturnal enuresis (NE) and its effect on the success of behavioral interventions. We also aimed to identify predictive factors related to success of behavioral interventions. METHODS: A total of 163 patients with NE and 160 patients without NE were enrolled to study. Urinalysis, urine culture, biochemical evaluation, plain radiography and urinary system ultrasonography were performed before treatment. Patients with NE received behavioral interventions for 3 months. Response to behavioral interventions was analyzed according to the presence and absence of SBO. Possible predictive factors for treatment success were also evaluated. RESULTS: Spina bifida occulta was detected in 47 (28.8 %) children at NE group and 24 (15.0 %) at control group (p = 0.138). Non monosymptomatic NE was more prevalent in patients with SBO (p < 0.001), and response to the treatment was significantly lower (p = 0.037). Presence of SBO (OR 8.8, 95 % CI 3.1-25.6), NE severity (OR 7.2, 95 % CI 2.4-21.7) and NE frequency on 3-day voiding diary (OR 9.4, 95 % CI 3.7-24.3) were significantly related to the success. CONCLUSIONS: The presence of SBO, severe NE and higher frequency of NE in voiding diary affect the response to behavioral interventions. Other treatment options such as medical treatment or enuresis alarm may be recommended for those patients. PMID- 26149637 TI - Oncological outcomes of a single but extensive transurethral resection followed by appropriate intra-vesical instillation therapy for newly diagnosed non-muscle invasive bladder cancer. AB - PURPOSE: A second transurethral resection (TUR) has been recommended by guidelines for high-grade non-muscle-invasive bladder cancer (NMIBC). However, the impact of surgical quality and post-TUR intra-vesical instillation therapy on oncologic outcome still remains unclear for newly diagnosed NMIBC. We conducted a retrospective cohort study for the patients who underwent extensive TUR followed by appropriate intra-vesical therapy for newly diagnosed NMIBC to assess their oncological outcomes. METHODS: We treated a cohort of 150 patients with NMIBC by our single but extensive TUR protocol at Hirosaki University Hospital between January 2005 and May 2012. The extensive TUR procedure comprised complete resection of all visible tumors including the muscle layer with a separate cold cup-biopsy of the marginal bottom. After visible tumors resection, additional resection for 5 mm wider area around the first surgical margin was performed. TUR was conducted by three expert urologists who had common agreement with the extensive TUR. All patients received 50 mg of epirubicin instillation immediately after TUR. Out of 150 patients, 74 patients who had multiple tumors or high-grade T1 disease received 40 mg of bacillus Calmette-Guerin Tokyo 172 strain once a week for six consecutive weeks. Patients who received second TUR were not included. The endpoints in this study were the recurrence-, progression-free, cancer-specific, and overall survivals. RESULTS: The 5-year recurrence- and progression-free survival rates were 77.2 and 98.0 %, respectively. The 5-year cancer-specific and overall survival rates were 98.0 and 92.6 %, respectively. The 5-year recurrence- and progression-free survival rates in high-grade T1 disease were 77.1 and 97.6 %, respectively, which were not significantly different from those in the cohort with Ta or low-grade BC. Cystoscopy revealed that 93 % of the patients were tumor-free, at the first cystoscopy, and four patients (3 %) showed progression to stage T2 or higher disease during the first year. CONCLUSION: While the present study has several limitations, including single-arm and retrospective nature, a single but extensive TUR combined with adjuvant intravesical treatment may have acceptable oncological outcomes in NMIBC patients. PMID- 26149638 TI - Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease. AB - Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Abeta) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Abeta directed therapeutics and their relevance. PMID- 26149639 TI - Study of serum paraoxonase & phospholipase activities in pregnant women in relation to birth weight. AB - AIMS: Low birth weight is an important issue due to its dreadful consequences in future. Well prevailing over the world, this is important in view of developing countries. Low birth weight is associated with high neonatal and infant mortality, lower trajectory of growth during childhood and adolescence, increases risk of non-communicable diseases during adult life. Oxidative stress is a major player among the various etiologies. Paraoxonase1 is an important antioxidant defense. Phospholipase is required to release free fatty acids from phosphoglycerides utilized for fetal growth. We conducted the study to look for the predictive value of serum paraoxonase and phospholipase. METHODS: With binding to Helsinki declaration and approval from Institutional Ethical Committee, we have selected 100 pregnant ladies. Serum PON1 arylesterase (ARE), lactonase (LACT) and serum phospholipase (PL) activities are measured. STATISTICAL ANALYSIS: We used SPSS 20.0 for linear and logistic regression models to assess the predictability of the ARE, LACT and PL for predicting the IUGR. RESULTS: R value increases in the order of maternal age, maternal weight, phospholipase, arylesterase, lactonase. Logistic regression analysis with different models and with birth weight as dependent factor, maternal age is flagged out as not significant. PL, LACT, ARE emerge out to be good predictors of IUGR. CONCLUSION: From this study we have concluded that PON1 LACT, ARE and serum PL, could be the newer markers IUGR in maternal serum. IUGR can be predicted beforehand by using PON1 LACT, PON1 ARE and serum phospholipase. This surely will help in timely diagnosis and treatment accordingly of possible adverse pregnancy outcome. PMID- 26149641 TI - Two thirds of NHS trusts forecast a deficit this year, up from a quarter last year. PMID- 26149640 TI - Elevation of miR-21, through targeting MKK3, may be involved in ischemia pretreatment protection from ischemia-reperfusion induced kidney injury. AB - BACKGROUND: Ischemia-reperfusion (IR) causes acute kidney injury (AKI), and ischemia pretreatment may exert protection. Mitogen-activated protein kinase kinase 3 (MKK3), which is involved in the signal transduction pathway in IR induced injury, is a potential target of miR-21. We aimed to verify the targeting regulation of miR-21 on MKK3 and to explore the effects of miR-21-mediated MKK3 expression changes in AKI. METHODS: Vectors containing the MKK3 3'UTR and mutated MKK3-3U-M were constructed and co-transfected with nonsense miR, miR-21-5p mimics or inhibitor in HEK293 cells. Gene expressions were detected by dual luciferase reporter assay. The effects of miR-21 on mRNA and protein of MKK3 were investigated in HK-2 cells. Male C57BL/6J mice were treated with ischemic preconditioning (IPC) and IR. Kidney functions were assessed through monitoring serum creatinine (Scr) and blood urea nitrogen (BUN). Pathological changes were observed and scored with histological samples of kidney. Expression levels of miR 21, MKK3, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha before and after IPC and IR were examined by real-time polymerase chain reaction and/or immunohistochemistry. RESULTS: miR-21 regulated the expression of MKK3 via 3'UTR. Following IR, MKK3, IL-6 and TNF-alpha levels were increased. Scr, BUN and pathological injuries were aggravated, and miR-21 expression was increased. IPC increased miR-21 levels ahead of IR and inhibited the increases in MKK3, IL-6 and TNF-alpha levels and the aggravation of Scr, BUN and pathological injuries. CONCLUSIONS: miR-21 targets MKK3 in vivo and in vitro, inhibiting the downstream factors IL-6 and TNF-alpha. Therefore, miR-21 might be involved in protection of IPC against IR of the kidney. PMID- 26149642 TI - RNA interference in adult Ascaris suum--an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite. AB - The sustainable control of animal parasitic nematodes requires the development of efficient functional genomics platforms to facilitate target validation and enhance anthelmintic discovery. Unfortunately, the utility of RNA interference (RNAi) for the validation of novel drug targets in nematode parasites remains problematic. Ascaris suum is an important veterinary parasite and a zoonotic pathogen. Here we show that adult A. suum is RNAi competent, and highlight the induction, spread and consistency of RNAi across multiple tissue types. This platform provides a new opportunity to undertake whole organism-, tissue- and cell-level gene function studies to enhance target validation processes for nematode parasites of veterinary/medical significance. PMID- 26149643 TI - Metastrongyloid infection by Aelurostrongylus abstrusus, Troglostrongylus brevior and Angiostrongylus chabaudi in a domestic cat. AB - The "cat lungworm", Aelurostrongylus abstrusus, affects cats worldwide. Recently, other cardio-pulmonary parasites, e.g. Troglostrongylus brevior and Angiostrongylus chabaudi, have been isolated from cats either for the first time or a long time after they were first described. This paper describes the first known mixed infection by A. abstrusus, T. brevior and A. chabaudi in a domestic cat. Biological and epidemiological implications of old and "new" metastrongyloid caused infections in cats are discussed. PMID- 26149644 TI - Anticytoplasm neutrophil antibodies-positive vasculitis with diffuse alveolar hemorrhage related to a spider bite. PMID- 26149646 TI - Selective growth of MFU-4l single crystals on microstructured plasma polymer coatings. AB - Single crystals of the metal-organic framework Ulm-4l(arge) (MFU-4l) can be grown site selectively on microtextured plasma polymer coatings comprising a pattern of alternating hydrophilic and hydrophobic domains. The crystals grow preferentially on the hydrophilic parts of the film surface. X-ray diffraction (XRD) shows that the cubic crystals have a high propensity to adhere with <1 0 0> orientation to the coating. PMID- 26149645 TI - Large-scale asynchronous and distributed multidimensional replica exchange molecular simulations and efficiency analysis. AB - We describe methods to perform replica exchange molecular dynamics (REMD) simulations asynchronously (ASyncRE). The methods are designed to facilitate large scale REMD simulations on grid computing networks consisting of heterogeneous and distributed computing environments as well as on homogeneous high-performance clusters. We have implemented these methods on NSF (National Science Foundation) XSEDE (Extreme Science and Engineering Discovery Environment) clusters and BOINC (Berkeley Open Infrastructure for Network Computing) distributed computing networks at Temple University and Brooklyn College at CUNY (the City University of New York). They are also being implemented on the IBM World Community Grid. To illustrate the methods, we have performed extensive (more than 60 ms in aggregate) simulations for the beta-cyclodextrin-heptanoate host-guest system in the context of one- and two-dimensional ASyncRE, and we used the results to estimate absolute binding free energies using the binding energy distribution analysis method. We propose ways to improve the efficiency of REMD simulations: these include increasing the number of exchanges attempted after a specified molecular dynamics (MD) period up to the fast exchange limit and/or adjusting the MD period to allow sufficient internal relaxation within each thermodynamic state. Although ASyncRE simulations generally require long MD periods (>picoseconds) per replica exchange cycle to minimize the overhead imposed by heterogeneous computing networks, we found that it is possible to reach an efficiency similar to conventional synchronous REMD, by optimizing the combination of the MD period and the number of exchanges attempted per cycle. PMID- 26149647 TI - Word production inconsistency of Singaporean-English-speaking adolescents with Down Syndrome. AB - BACKGROUND: The nature of speech disorders in individuals with Down Syndrome (DS) remains controversial despite various explanations put forth in the literature to account for the observed speech profiles. A high level of word production inconsistency in children with DS has led researchers to query whether the inconsistency continues into adolescence, and if the inconsistency stems from inconsistent phonological disorder (IPD) or childhood apraxia of speech (CAS). Of the studies that have been published, most suggest that the speech profile of individuals with DS is delayed, while a few recent studies suggest a combination of delayed and disordered patterns. However, no studies have explored the nature of word production inconsistency in this population, and the relationship between word production inconsistency, receptive vocabulary and severity of speech disorder. AIMS: To investigate in a pilot study the extent of word production inconsistency in adolescents with DS and to examine the correlations between word production inconsistency, measures of receptive vocabulary, severity of speech disorder and oromotor skills in adolescents with DS. METHODS & PROCEDURES: The participants were 32 native speakers of Singaporean-English adolescents, comprising 16 participants with DS and 16 typically developing (TD) participants. The participants completed a battery of standardized speech and language assessments, including The Diagnostic Evaluation of Articulation and Phonology (DEAP) assessment. Results from each test were correlated to determine relationships. Qualitative analyses were also carried out on all the data collected. OUTCOMES & RESULTS: In this study, seven out of 16 participants with DS scored above 40% on word production inconsistency, a diagnostic criterion for IPD. In addition, all participants with DS performed poorly on the oromotor assessment of DEAP. The overall speech profile observed did not exactly correspond with the cluster symptoms observed in children with IPD or CAS. CONCLUSIONS & IMPLICATIONS: Word production inconsistency is a noticeable feature in the speech of individuals with DS. In addition, the speech profiles of individuals with DS consist of atypical and unusual errors alongside developmental errors. Significant correlations were found between the measures investigated, suggesting that speech disorder in DS is multifactorial. The results from this study will help to improve differential diagnosis of speech disorders and individualized treatment plans in the population with DS. PMID- 26149648 TI - Regulation of OPG and RANKL expressed by human dental follicle cells in osteoclastogenesis. AB - We investigate whether the expression of the receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) in human dental follicle cells (HDFCs) regulated by colony stimulating factor 1 (CSF-1), parathyroid hormone related protein (PTHrP) and bone morphogenetic protein-2 (BMP-2) contributes to osteoclastogenesis. Adolescent human impacted third mandibular molars were used to separate HDFCs. These cells were incubated with PTHrP (10 ng/ml), CSF-1 (25 ng/ml), or BMP-2 (100 ng/ml) for 0.5, 1, 3, 6 and 12 h. The expression of OPG and RANKL was investigated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Two co-culture systems and tartrate-resistant acid phosphatase (TRAP) staining were used to examine osteoclast formation. Scanning electron microscopy was utilized for the resorption pit assay. RANKL and OPG were expressed innately in HDFCs. Exogenous PTHrP, CSF-1 and BMP-2 chronologically regulated the expression of RANKL and OPG in HDFCs. PTHrP and CSF 1 had similar regulative patterns leading to the up-regulated expression of RANKL and the down-regulated expression of OPG and opposite for BMP-2. The number of TRAP-positive peripheral blood mononuclear cells (PBMCs) slightly increased in contacted co-culture of HDFCs and PBMCs, whereas secreted OPG from HDFCs inhibited osteoclastogenesis in the transwell co-culture system. Contacted co culture of HDFCs and PBMCs exhibited small and shallow resorption pits, whereas in the transwell co-culture system, secreted OPG from HDFCs reduced the resorption pits, reflecting the difference in osteoclast production. Collectively, we found a dual action of HDFCs in osteoclastogenesis; moreover, PTHrP, CSF-1 and BMP-2 might influence osteoclastogenesis by regulating the expression of RANKL and OPG in HDFCs. PMID- 26149649 TI - Single amino acid changes in naked mole rat may reveal new anti-cancer mechanisms in mammals. AB - BACKGROUND: The naked mole rat (NMR, Heterocephalus glaber) is a long-lived rodent model with multiple extraordinary traits. They live underground and have been known to live for up to thirty years, much longer than similar-sized mice. Moreover, congenital cancer or experimentally induced cancer genesis could not been observed in this rodent so far. Such unique biochemical and physiological characteristics lead them to become a popular model for cancer research. RESULTS: In this paper, a genome-wide comparative analysis was conducted based on the genomes of NMR and several other mammals. First, all the annotated proteins of NMR were searched against 11 selected mammalian genomes to verify their occurrence in these organisms. Among them, 66 NMR genes were not detected in other 11 mammals, almost all of which present alkalinity isoelectric points. In contrast, a total of 89 genes that are present in all of the 11 organisms could not be found in NMR genome. Among them, 3 genes are known to be related to cancer development. Finally, we identified NMR-specific single amino acid change (SAAC) events for the proteins that are present in both NMR and other mammals. KEGG pathway database was also used to investigate the metabolic processes in which these SAAC proteins may be involved. These genes were significantly enriched in two known cancer pathways, "Pathways in cancer" and "Pancreatic cancer". In the "Pancreatic cancer" pathway, 3 out of 6 paths leading to DNA duplication appeared to be affected by direct connection to the SAAC genes in NMR. In addition, a significant number of other SAAC genes enriched in several cancer-related pathways have been known to be associated with a variety of cancers, implying that many of them may be also related to tumor genesis in mammals. CONCLUSIONS: Overall, our results not only can be used to find possible genes involved in physiological mechanism of NMR but also provide new clues for the anti-cancer mechanism of NMR. PMID- 26149650 TI - Conservation of the coding regions of the glycine N-acyltransferase gene further suggests that glycine conjugation is an essential detoxification pathway. AB - Thorough investigation of the glycine conjugation pathway has been neglected. No defect of the glycine conjugation pathway has been reported and this could reflect the essential role of glycine conjugation in hepatic metabolism. Therefore, we hypothesised that genetic variation in the open reading frame (ORF) of the GLYAT gene should be low and that deleterious alleles would be found at low frequencies. This hypothesis was investigated by analysing the genetic variation of the human GLYAT ORF using data available in public databases. We also sequenced the GLYAT ORF of a small cohort of South African Afrikaner Caucasian individuals. In total, data from 1537 individuals was analysed. The two most prominent GLYAT haplotypes in all populations analysed, were S156 (70%) and T17S156 (20%). The S156C199 and S156H131 haplotypes, which have a negative effect on the enzyme activity of a recombinant human GLYAT, were detected at very low frequencies. In the Afrikaner Caucasian cohort a novel Q61L SNP occurring at a high frequency (12%) was detected. The results of this study indicated that the GLYAT ORF is highly conserved and supported the hypothesis that the glycine conjugation pathway is an essential detoxification pathway. These findings emphasise the importance of future investigations to determine the in vivo capacity of the glycine conjugation pathway for the detoxification of benzoate and other xenobiotics. PMID- 26149651 TI - Two novel UBR1 gene mutations in a patient with Johanson Blizzard Syndrome: A mild phenotype without mental retardation. AB - Johanson-Blizzard Syndrome (JBS) (MIM #243800) is a rare autosomal recessive genetic disorder characterized by exocrine pancreatic insufficiency, abnormal facial appearance and varying degrees of mental retardation. Mutations in UBR1 gene (MIM *605981) are considered to be responsible for the syndrome. Here, we report a 3 year-old mentally normal JBS girl. The patient presented with exocrine pancreatic insufficiency as well as failure-to-thrive. On dysmorphological examination, she was noted to have an abnormal hair pattern with frontal upsweep and alae nasi hypoplasia. With these findings, JBS diagnosis was established clinically. Molecular analysis of the UBR1 gene revealed two inherited novel mutations; one coming from each parent. These novel mutations were c. 1280T>G and c. 2432+5G>C, and they were found to be disease causing via in-silico analysis. In conclusion, for patients with longstanding exocrine pancreatic insufficiency, it should be considered as being symptomatic of a far broader picture. To omit connection with rare genetic diseases, such as Johanson-Blizzard Syndrome, a detailed dysmorphological examination ought to be performed. PMID- 26149652 TI - Whole-genome expression analysis of Rice black-streaked dwarf virus in different plant hosts and small brown planthopper. AB - Rice black-streaked dwarf virus (RBSDV) can infect a number of gramineous plants and cause severe crop yield losses in southeast Asian countries. The virus is transmitted by small brown planthopper (SBPH) in a persistent circulative manner. The interactions between RBSDV and its different hosts remain unknown. Besides, how the virus adjusts itself to infect different hosts is unclear. In the present study, the relative RNA levels of the thirteen RBSDV genes in rice, maize, wheat, and SBPH were measured by real-time quantitative PCR. P7-1 and P10 genes were predominantly expressed whereas P8 and P7-2 genes were expressed at low levels in plant hosts. Similar to the expression in rice, P7-1 was the most abundantly expressed gene and P8 was expressed at the lowest level in SBPH, indicating that RBSDV adopts the same strategy to infect distinct hosts. The high expression levels of the P7-1 gene in both plants and insect suggest that it can be used as the target gene for disease diagnostics. However, the expression levels of some genes varied from host to host. P5-1, P6 and P9-1, the components of the RBSDV viroplasm, are differentially expressed in different hosts. Moreover, western blot analysis showed that the quantity of the P9-1 protein was more abundant in SBPH than in plant hosts. These data indicate that the virus may adjust its own gene expression to replicate in different hosts. Analysis of time course of gene expression revealed that P7-1 stands out as the only gene highly expressed at the earliest time point and its expression precedes all others throughout infection from 8 to 24days post-inoculation. The high expression levels of the P7-1 gene suggest that it plays a significant role in RBSDV-host interactions. PMID- 26149653 TI - Role of gelsolin in cell proliferation and invasion of human hepatocellular carcinoma cells. AB - OBJECTIVE: Gelsolin (GSN), one of the most important actin structure regulating proteins, has been implicated in the oncogenesis of some cancers. In this study, we investigated the expression of GSN in hepatocellular carcinoma (HCC) and revealed its potential mechanisms. The mRNA and protein levels of GSN were overexpressed in HCC cells and HCC tissues compared to adjacent noncancerous tissues. GSN expression was correlated with venous invasion (P=0.0199) and Edmonson grading (P=0.0344) expression in HCC. Overexpression of GSN in Huh7 and SMMC-7721 cells significantly promoted cell proliferation and the number of MatrigelTM-invading cells compared with control cells, with increased expression of matrix metalloproteinase MCL-1, MMP-2 and MMP-9, a key regulator of growth and invasion. In contrast, knockdown of GSN expression with small interfering RNA (siRNA) in MHCC-97L and MHCC-97H cell lines resulted in decreased cell viability and cell invasion. Our findings indicated that GSN expression promoted tumor associated phenotypes by facilitating proliferative and invasive capacities of HCC cells, which might serve as a potential therapeutic target for HCC treatment. PMID- 26149654 TI - Fast fish face fewer mitochondrial mutations: Patterns of dN/dS across fish mitogenomes. AB - Mitochondrial DNA is routinely used to answer a variety of biological questions; and there is growing evidence suggesting that its accumulation of mutations is influenced by life history, effective population size and cellular energy requirements. This study examines the influence of phylogenetic patterns of metabolic activity on the evolution of mitochondrial DNA in fishes, given energy requirements associated with high performance versus sedentary life histories. It was determined that all 13 protein coding genes of the mitogenome experience a relaxation of purifying selection in sedentary fishes. This phenomenon was not detected in nuclear housekeeping genes, suggesting that it can be explained by the energy requirements of these groups, and possibly their effective population sizes. This study also examined the subunit binding sites of two subunits of cytochrome c oxidase (COXI and COXIII), and did not detect any differences in selection between these groups of fishes. These cytochrome c oxidase subunits interact with subunits that are encoded by the nuclear genome and it has been suggested that a unique form of coevolution occurs between these genomes in order to maintain function, and may have implications for speciation. Although this was not a main focus of this study, our preliminary results suggest that substitutions in subunit binding site regions are rare. The results from this study add to the growing literature on the complex relationship between mitochondrial DNA and the evolution of life histories across the tree of life. PMID- 26149655 TI - Association of KEAP1 and NFE2L2 polymorphisms with temporal lobe epilepsy and drug resistant epilepsy. AB - BACKGROUND AND AIMS: Temporal lobe epilepsy (TLE) is a prevalent form of epilepsy. TLE contributes to the majority of drug resistant epilepsy (DRE) cases and is associated with genetic factors. Kelch-like ECH-associated protein 1 (KEAP1)/Nuclear erythroid 2-related factor 2 (known as NFE2L2 or Nrf2) association has been implicated in neuroprotection due to induction of antioxidant enzymes. The association of one single KEAP1 gene nucleotide polymorphism (SNP) and nine NFE2L2 gene SNPs with TLE and DRE were examined to determine whether these SNPs influenced the risk of TLE and DRE in a Han population. SUBJECTS AND METHODS: A total of 184 TLE patients (including 72 DRE patients) and 183 controls were included in this analysis. The SNaPshot Multiplex kit was used to assess the genotypes. RESULTS: A NFE2L2 gene haplotype was identified as a risk factor for TLE (OR=7.11, 95% CI 1.53-32.98). Additionally, rs2706110 G>A in the NFE2L2 gene and rs1048290 C>G in the KEAP1 gene showed a significant risk for and a protective effect against DRE, respectively. CONCLUSION: Our findings suggest that variations in NFE2L2 gene increase the risk of TLE and DRE but that variations in KEAP1 gene play a protective role for DRE. PMID- 26149656 TI - Role of long purine stretches in controlling the expression of genes associated with neurological disorders. AB - Purine repeat sequences present in the human genome are known to act as hotspots for mutations leading to chromosomal imbalances. It is established that large purine repeats (PRs) form stable DNA triplex structure which can inhibit gene expression. Friedreich's ataxia (FRDA), the autosomal neurodegenerative disorder is the only human disease known so far, where a large purine (GAA) repeat in the FXN gene is known to inhibit the expression of frataxin protein. We explored the hidden purine repeats (PRn with n >= 200) if any, in the human genome to find out how they are associated with neurological disorders. The results showed 28 PRs, which are mostly restricted to the intronic regions. Interestingly, the transcriptome expression analysis of PR-carrying genes (PR-genes) revealed that most of them are down-regulated in neurological disorders (autism, Alzheimer's disease, schizophrenia, epilepsy, mental retardation, Parkinson's disease, brain tumor) as compared to that in healthy controls. The altered gene expression in brain disorders can be interpreted in terms of a possible expansion of purine repeats leading to formation of very stable DNA-triplex and/or alleviation of the repair enzymes and/or other unknown cellular factors. Interactome analysis identified four PR-genes in signaling pathways whose dysregulation is correlated directly with pathogenesis: GRK5 and KLK6 in Alzheimer's disease; FGF14 in craniosynostosis, mental retardation and FLT1 in neuroferritinopathy. By virtue of being mutational hotspots and their ability to form DNA-triplex, purine repeats in genome disturb the genome integrity and interfere with the transcriptional regulation. However, validation of the disease linkage of PR genes can be validated using knock-out techniques. PMID- 26149657 TI - RPS24 knockdown inhibits colorectal cancer cell migration and proliferation in vitro. AB - Besides new proteins synthesis, ribosomal protein has a role in extra-ribosomal functions, which are related to many diseases, such as Diamond-Blackfan anemia, hypoplasia, and cell apoptosis. However, the importance of RPS24 in human colon cancer is largely unknown. In this study, RPS24 gene expression was significantly inhibited in human colon cancer HCT116 and HT-29 cells using a lentivirus shRNA approach. Knockdown of RPS24 expression significantly inhibited cell proliferation, colony formation, cell migration and arrested cell in S phase. The results demonstrated for the first time that RPS24 gene had a critical role in human colon cancer. Therefore, our findings indicated that RPS24 gene may be a promising biomarker for therapy in human colon cancer and may have a potential application in the diagnosis or treatment of human colon cancer. PMID- 26149658 TI - Segregation of a novel MLH1 mutation in an Iranian Lynch syndrome family. AB - Lynch syndrome is an autosomal dominant disorder caused by germline mutations in mismatch repair (MMR) genes. The main feature of this disorder is an early onset of hereditary colorectal cancer in addition to other cancers arising from different tissues. Here, we report an Iranian family with several members affected with Lynch syndrome related cancers. Exome sequencing with focus on 14 genes related with hereditary colorectal cancer has shown a novel mutation in exon 19 of MLH1 gene (c.2133delC, p.Trp712Gly fs*71). This mutation is located in a region coding for the functional domain for the interaction with MLH3/PMS1/PMS2. As some clinical aspects of the disorder have been shown to be associated with certain mutations, identification of causative mutation in each family has implications for surveillance protocols. PMID- 26149659 TI - Impact of the source of hematopoietic stem cell in unrelated transplants: comparison between 10/10, 9/10-HLA matched donors and cord blood. AB - In absence of available matched-related or unrelated donor (MUD), mismatched unrelated donors (MMUD) and unrelated cord blood (UCB) are both considered to be suitable donors, with similar post-transplant overall survival. In most of these retrospective comparisons, HLA typing of adult donors was performed at eight loci. The aim of this study was to compare the outcome of patients transplanted from UCB (N = 64) with those transplanted from 9/10-HLA MMUD (N = 84) or 10/10 HLA MUD (N = 196). In multivariate analysis, UCB was associated with less Grade II-IV acute GVHD in comparison with MUD (aHR 1.97, 95% CI 1.19-3.27, P = 0.009) and MMUD transplants (aHR 1.79, 95% CI 1.02-3.15, P = 0.042), while the cumulative incidence of chronic GVHD was not significantly different between the three groups. Overall survival (OS), non-relapse mortality, and relapse were not different between MMUD and UCB transplantation, whereas OS was impaired after UCB in comparison with MUD (aHR 0.65, 95% CI 0.43-0.99, P = 0.043). Factors also impacting OS were the donor/recipient CMV serostatus (Donor-/Recipient+ aHR 1.76, 95% CI 1.23-2.52, P = 0.002 compared with D-/R-), the donor/recipient gender combination (Female/Male versus other combinations aHR 1.57, 95% CI 1.11-2.22, P = 0.012) and disease risk (aHR 1.58, 95% CI 1.05-2.38, P = 0.027 for high vs. low risk disease). Our data confirm that UCB and 9/10-HLA MMUD are both relevant alternative options when no 10/10-HLA donor is available. Donor/recipient gender combination and CMV serostatus had a significant impact on survival and may be taken into account, along with donor type, in the setting of MMUD and UCB transplants. PMID- 26149660 TI - A Hyaluronic Acid-Rich Node and Duct System in Which Pluripotent Adult Stem Cells Circulate. AB - Regenerative medicine is in demand of adult pluripotent stem cells (PSCs). The "Bonghan System (BHS)" was discovered and suggested to contain cells with regenerative capacity in the early 1960s. It had been ignored for a long time due to the lack of sufficient details of experiments, but about 37 years after the initial report, the BHS was rediscovered and named as the "primo vascular system." Recently, we have discovered a similar structure, which contained a high level of hyaluronic acid, and hence, named the structure as hyaluronic acid-rich node and duct system (HAR-NDS). Here we discuss the HAR-NDS concept starting from the discovery of BHS, and findings pointing to its importance in regenerative medicine. This HAR-NDS contained adult PSCs, called node and duct stem cells (NDSCs), which appeared to circulate in it. We describe the evidence that NDSCs can differentiate into hemangioblasts that further produced differentiated blood cells. The NDSCs had a potential to differentiate into neuronal cells and hepatocytes; thus, NDSCs had a capability to become cells from all three germ layers. This system appears to be a promising alternative source of adult stem cells that can be easily delivered to their target tissues and participate in tissue regeneration. PMID- 26149661 TI - Self-assembly mechanism of nanoparticles of Ni-based Prussian Blue analogues at the air/liquid interface: a synchrotron X-ray reflectivity study. AB - Prussian Blue analogue (PBA) nanoparticles can be self-assembled at air/liquid interfaces to build novel materials with interesting magnetic features. Herein, we study the influence of the size of PBA Cs0.4 Ni[Cr(CN)6 ]0.9 and K0.25 Ni[Fe(CN)6 ]0.75 nanoparticles on the self-assembly behavior by synchrotron X-ray reflectivity. Both nanoparticles show similar Z-potential values. The phospholipid dipalmitoylphosphatidylcholine and the amino surfactant dimethyldioctadecylammonium have been used as Langmuir monolayers to anchor the PBA nanoparticles and study the interplay of forces directing the self-assembly of the nanoparticles at the surfactant/liquid interface. Whereas Cs0.4 Ni[Cr(CN)6 ]0.9 nanoparticles with a diameter of 8 nm form an incomplete layer at the surfactant/water interface, the larger K0.25 Ni[Fe(CN)6 ]0.75 nanoparticles with a diameter of 20 nm generate complete layers that can be stacked to one another. The size of the PBA nanoparticles is the main parameter determining the final arrangement at the air/liquid interface, due to the different extent of interparticle interaction. This study aims at the rationale design of PBA nanoparticles for an effective interfacial self-assembly, ultimately leading to functional materials. PMID- 26149662 TI - A Preliminary Quantitative Comparison of Vibratory Amplitude Using Rigid and Flexible Stroboscopic Assessment. AB - STUDY OBJECTIVE: The purpose of this study was to establish preliminary, quantitative data on amplitude of vibration during stroboscopic assessment in healthy speakers with normal voice characteristics. Amplitude of vocal fold vibration is a core physiological parameter used in diagnosing voice disorders, yet quantitative data are lacking to guide the determination of what constitutes normal vibratory amplitude. METHODS/STUDY DESIGN: Eleven participants were assessed during sustained vowel production using rigid and flexible endoscopy with stroboscopy. Still images were extracted from digital recordings of a sustained /i/ produced at a comfortable pitch and loudness, with F0 controlled so that levels were within +/-15% of each participant's comfortable mean level as determined from connected speech. Glottal width (GW), true vocal fold (TVF) length, and TVF width were measured from still frames representing the maximum open phase of the vibratory cycle. To control for anatomic and magnification differences across participants, GW was normalized to TVF length. GW as a ratio of TVF width was also computed for comparison with prior studies. RESULTS: Mean values and standard deviations were computed for the normalized measures. Paired t tests showed no significant differences between rigid and flexible endoscopy methods. Interrater and intrarater reliability values for raw measurements were found to be high (0.89-0.99). CONCLUSIONS: These preliminary quantitative data may be helpful in determining normality or abnormality of vocal fold vibration. Results indicate that quantified amplitude of vibration is similar between endoscopic methods, a clinically relevant finding for individuals performing and interpreting stroboscopic assessments. PMID- 26149663 TI - Everyday life as a bridge over troubled water. PMID- 26149664 TI - Influence of the Multivalency of Ultrashort Arg-Trp-Based Antimicrobial Peptides (AMP) on Their Antibacterial Activity. AB - Peptide dendrimers are a class of molecules of high interest in the search for new antibiotics. We used microwave-assisted, copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC; "click" chemistry) for the simple and versatile synthesis of a new class of multivalent antimicrobial peptides (AMPs) containing solely arginine and tryptophan residues. To investigate the influence of multivalency on antibacterial activity, short solid-phase- synthesized azide-modified Arg-Trp containing peptides were "clicked" to three different alkyne-modified benzene scaffolds to access scaffolds with one, two, or three peptides. The antibacterial activity of 15 new AMPs was investigated by minimal inhibitory concentration (MIC) assays on five different bacterial strains, including a multidrug-resistant Staphylococcus aureus (MRSA) strain. With ultrashort (2-3 residues) peptides, a clear synergistic effect of the trivalent display was observed, whereas this effect was not apparent with longer peptides. The best candidates showed activities in the low-micromolar range against Gram-positive MRSA. Surprisingly, the best activity against Gram-negative Acinetobacter baumannii was observed with an ultrashort dipeptide on the trivalent scaffold (MIC: 7.5 MUM). The hemolytic activity was explored for the three most active peptides. At concentrations ten times the MIC values, <1 % hemolysis of red blood cells was observed. PMID- 26149665 TI - Latent classes of childhood trauma exposure predict the development of behavioral health outcomes in adolescence and young adulthood. AB - BACKGROUND: To develop latent classes of exposure to traumatic experiences before the age of 13 years in an urban community sample and to use these latent classes to predict the development of negative behavioral outcomes in adolescence and young adulthood. METHOD: A total of 1815 participants in an epidemiologically based, randomized field trial as children completed comprehensive psychiatric assessments as young adults. Reported experiences of nine traumatic experiences before age 13 years were used in a latent class analysis to create latent profiles of traumatic experiences. Latent classes were used to predict psychiatric outcomes at age ?13 years, criminal convictions, physical health problems and traumatic experiences reported in young adulthood. RESULTS: Three latent classes of childhood traumatic experiences were supported by the data. One class (8% of sample), primarily female, was characterized by experiences of sexual assault and reported significantly higher rates of a range of psychiatric outcomes by young adulthood. Another class (8%), primarily male, was characterized by experiences of violence exposure and reported higher levels of antisocial personality disorder and post-traumatic stress. The final class (84%) reported low levels of childhood traumatic experiences. Parental psychopathology was related to membership in the sexual assault group. CONCLUSIONS: Classes of childhood traumatic experiences predict specific psychiatric and behavioral outcomes in adolescence and young adulthood. The long-term adverse effects of childhood traumas are primarily concentrated in victims of sexual and non-sexual violence. Gender emerged as a key covariate in the classes of trauma exposure and outcomes. PMID- 26149666 TI - CD14(hi)CD16+ monocytes phagocytose antibody-opsonised Plasmodium falciparum infected erythrocytes more efficiently than other monocyte subsets, and require CD16 and complement to do so. AB - BACKGROUND: With more than 600,000 deaths from malaria, mainly of children under five years old and caused by infection with Plasmodium falciparum, comes an urgent need for an effective anti-malaria vaccine. Limited details on the mechanisms of protective immunity are a barrier to vaccine development. Antibodies play an important role in immunity to malaria and monocytes are key effectors in antibody-mediated protection by phagocytosing antibody-opsonised infected erythrocytes (IE). Eliciting antibodies that enhance phagocytosis of IE is therefore an important potential component of an effective vaccine, requiring robust assays to determine the ability of elicited antibodies to stimulate this in vivo. The mechanisms by which monocytes ingest IE and the nature of the monocytes which do so are unknown. METHODS: Purified trophozoite-stage P. falciparum IE were stained with ethidium bromide, opsonised with anti-erythrocyte antibodies and incubated with fresh whole blood. Phagocytosis of IE and TNF production by individual monocyte subsets was measured by flow cytometry. Ingestion of IE was confirmed by imaging flow cytometry. RESULTS: CD14(hi)CD16+ monocytes phagocytosed antibody-opsonised IE and produced TNF more efficiently than CD14(hi)CD16- and CD14(lo)CD16+ monocytes. Blocking experiments showed that Fcgamma receptor IIIa (CD16) but not Fcgamma receptor IIa (CD32a) or Fcgamma receptor I (CD64) was necessary for phagocytosis. CD14(hi)CD16+ monocytes ingested antibody-opsonised IE when peripheral blood mononuclear cells were reconstituted with autologous serum but not heat-inactivated autologous serum. Antibody-opsonised IE were rapidly opsonised with complement component C3 in serum (t1/2 = 2-3 minutes) and phagocytosis of antibody-opsonised IE was inhibited in a dose-dependent manner by an inhibitor of C3 activation, compstatin. Compared to other monocyte subsets, CD14(hi)CD16+ monocytes expressed the highest levels of complement receptor 4 (CD11c) and activated complement receptor 3 (CD11b) subunits. CONCLUSIONS: We show a special role for CD14(hi)CD16+ monocytes in phagocytosing opsonised P. falciparum IE and production of TNF. While ingestion was mediated by Fcgamma receptor IIIa, this receptor was not sufficient to allow phagocytosis; despite opsonisation with antibody, phagocytosis of IE also required complement opsonisation. Assays which measure the ability of vaccines to elicit a protective antibody response to P. falciparum should consider their ability to promote phagocytosis and fix complement. PMID- 26149667 TI - Bioactive peptides identified in thornback ray skin's gelatin hydrolysates by proteases from Bacillus subtilis and Bacillus amyloliquefaciens. AB - Thornback ray skin gelatin has been hydrolyzed with two different proteases in order to obtain peptides with ACE inhibitory and antioxidant activity. Hydrolysates with protease from Bacillus subtilis A26 (TRGH-A26) displayed ACE inhibitory activity with an IC50 value of 0.94 MUg/MUL whereas Neutrase(r) hydrolysate from Bacillus amyloliquefaciens (TRGH-Neutrase) showed an IC50 value of 2.07 MUg/MUL. Regarding antioxidant activity, IC50 values of 1.98 and 21.2 MUg/MUL in TRGH-A26 and TRGH-Neutrase, respectively, were obtained using the DPPH radical-scavenging assay. The most active fractions identified by size-exclusion chromatography were further purified by RP-HPLC and analysed using nanoESI-LC MS/MS to identify the sequence of the peptides. APGAP was the most active peptide inTRGH-A26 for ACE inhibitory activity with an IC50 value of 170 MUM, whereas GIPGAP showed the best ACE inhibitory activity in TRGH-Neutrase sample with an IC50 value of 27.9 MUM. The highest antioxidant activity was identified in peptide AVGAT, showing a 33% of activity at 3mg/mL using the DPPH radical scavenging assay. The obtained results proved the potential of thornback ray skin gelatin hydrolysates as a source of bioactive peptides. STATEMENT OF SIGNIFICANCE: This study describes a peptidomic approach for the identification of ACE-inhibitory and antioxidant peptides generated from thornback ray gelatin (Raja clavata) hydrolysates from Bacillus subtilis A26 and Bacillus amyloliquefaciens Neutrase(r) enzymes and expose the potential of thornback ray gelatin hydrolysate as a source of bioactive peptides. In this sense, the decrease of systolic blood pressure is one of the main measurements considered in public health for the treatment of cardiovascular diseases, stroke and even end stage renal disease. Traditionally, synthetic drugs such as captopril and enalapril have been used as ACE inhibitors despite their secondary effects, but the finding of new sources for the generation of natural bioactive peptides such as thornback ray muscle results is very important in the knowledge of less hostile but highly effective antihypertensive peptides as well as the development of new uses for waste and by-products generated from marine products, helping to solve the already existing environmental problem affecting this industry. PMID- 26149669 TI - The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. AB - CONTEXT: Tobacco smoke includes a mix of carcinogens implicated in the etiology of bladder cancer (BC) and renal cell cancer (RCC). OBJECTIVE: We reviewed the impact of tobacco exposure on BCC and RCC incidence and mortality, and whether smoking cessation decreases the risk. EVIDENCE ACQUISITION: A systematic review of original articles in English was performed in August 2013. Meta-analysis of risks was performed using adjusted risk ratios where available. Publication bias was assessed using Begg and Egger tests. EVIDENCE SYNTHESIS: We identified 2683 papers, of which 107 fulfilled our inclusion criteria, of which 83 studies investigated BC and 24 investigated RCC. The pooled relative risk (RR) of BC incidence was 2.58 (95% confidence interval [CI] 2.37-2.80) for all smokers, 3.47 (3.07-3.91) for current smokers, and 2.04 (1.85-2.25) for former smokers. The corresponding pooled RR of BC disease-specific mortality (DSM) was 1.47 (1.24 1.75), 1.53 (1.12-2.09) and 1.44 (0.99-2.11). The pooled RR of RCC incidence was 1.31 (1.22-1.40) for all smokers, 1.36 (1.19-1.56) for current smokers, and 1.16 (1.08-1.25) for former smokers. The corresponding RCC DSM risk was 1.23 (1.08 1.40), 1.37 (1.19-1.59), and 1.02 (0.90-1.15). CONCLUSIONS: We present an up-to date review of tobacco smoking and BC and RCC incidence and mortality. Tobacco smoking significantly increases the risk of BC and RCC incidence. BC incidence and DSM risk are greatest in current smokers and lowest in former smokers, indicating that smoking cessation confers benefit. We found that secondhand smoke exposure is associated with a significant increase in BC risk. PATIENT SUMMARY: Tobacco smoking affects the development and progression of bladder cancer and renal cell cancer. Smoking cessation reduces the risks of developing and dying from these common cancers. We quantify these risks using the most up-to-date results published in the literature. PMID- 26149668 TI - Characterization of Clinical Cases of Collecting Duct Carcinoma of the Kidney Assessed by Comprehensive Genomic Profiling. AB - BACKGROUND: Collecting duct carcinoma (CDC) is a rare type of renal cell carcinoma (RCC) originating from the renal medulla. Clinical outcomes are poor, and there are no consensus guidelines to guide therapy. OBJECTIVE: To determine genomic alterations (GAs) in a series of patients with locally advanced or metastatic CDC for whom genomic profiling was performed during the course of clinical care. DESIGN, SETTING, AND PARTICIPANTS: Formalin-fixed, paraffin embedded blocks or slides were obtained for 17 patients with CDC. DNA was extracted and comprehensive genomic profiling was performed in a laboratory certified under the Clinical Laboratory Improvement Amendments. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bayesian algorithms and local alignment algorithms were used to detect substitutions and insertions/deletions, respectively. A comparison to normal control samples was used to detect copy number alterations. Clinically relevant GAs (CRGAs) were defined as those linked to approved or investigational targeted therapies. RESULTS AND LIMITATIONS: The median age in the cohort was 53 yr (range 26-73), and 14 primary tumors and three metastatic sites assessed. A total of 36 GAs were detected in this series of patients, with an average of 2.1 GAs per case. The most common GAs were in NF2 (5/17, 29%), SETD2 (4/17, 24%), SMARCB1 (3/17, 18%), and CDKN2A (2/17, 12%). Of nine cases assessed for FH GAs, two patients had FH homozygous loss. A limitation is that targeted interrogation of genes known to be implicated in other cancers was performed, so mutations outside of these cannot be excluded. CONCLUSIONS: Recurrent CRGAs were detected in this series of CDC cases and suggest a possible benefit from targeted therapy. In particular, mTOR inhibitors may be of interest in patients with NF2 alterations. Alterations in FH and SMARCB1 also occurred in a mutually exclusive manner to NF2 alterations. PATIENT SUMMARY: This report provides important genomic insights into collecting duct carcinoma, a rare type of renal cell carcinoma with a very aggressive course. These insights could further rationalize the use of targeted therapies for rare tumors according to the individual genomic alterations harbored. PMID- 26149670 TI - Cobalamin deficiency causing severe hemolytic anemia: a pernicious presentation. PMID- 26149671 TI - Good Advice from Anthony Bourdain. PMID- 26149672 TI - Disseminated mycobacterial infection and scabies infestation. PMID- 26149673 TI - Incidental cerebral toxocarosis as confirmed by cerebrospinal fluid cytology. PMID- 26149674 TI - Thrombotic thrombocytopenia purpura: a potentially reversible cause of complete heart block. PMID- 26149675 TI - Food Addiction: Clinical Reality or Mythology. PMID- 26149676 TI - Sleep Disturbance Partially Mediates the Relationship Between Intimate Partner Violence and Physical/Mental Health in Women and Men. AB - Intimate partner violence (IPV) is a worldwide health concern and an important risk factor for poor mental/physical health in both women and men. Little is known about whether IPV leads to sleep disturbance. However, sleep problems may be common in the context of IPV and may mediate relationships with mental/physical health. Data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS) were used ( N = 34,975). IPV was assessed in female and male participants for any history of being threatened by, physically hurt by, or forced to have sex with an intimate partner (THREAT, HURT, and SEX, respectively), and, further, as being forced to have sex with or physically injured by an intimate partner within the past year (SEXyr and HURTyr, respectively). These survey items were coded yes/no. Sleep disturbance was assessed as difficulty falling asleep, staying asleep, or sleeping too much at least 6 of the last 14 days. Logistic regression analyses, adjusted for age, sex, race, income, education, and physical/mental health, assessed whether IPV predicted sleep disturbance. Sobel-Goodman tests assessed whether relationships between IPV and physical/mental health were partially mediated by sleep disturbance. All IPV variables were associated with sleep disturbance, even after adjusting for the effects of age, sex, race/ethnicity, income, education, employment, marital status, physical health and mental health. THREAT was associated with sleep disturbance (odds ratio [OR] = 2.798, p < .0001), as was HURT (OR = 2.683, p < .0001), SEX (OR = 3.237, p < .0001), SEXyr (OR = 7.741, p < .0001), and HURTyr (OR = 7.497, p < .0001). In mediation analyses, all IPV variables were associated with mental health ( p < .0001), and all were associated with physical health ( p < .007) except SEXyr. Sleep disturbance partially mediated all relationships (Sobel p < .0005 for all tests). Mediation was around 30%, ranging from 18% (HURTyr and mental health) to 41% (HURT and physical health). IPV was strongly associated with current sleep disturbance above the effect of demographics and overall mental/physical health, even if the IPV happened in the past. Furthermore, sleep disturbance partially mediates the relationship between IPV and mental/physical health. Sleep interventions may potentially mitigate negative effects of IPV. PMID- 26149677 TI - Impact of Meditation on Mental Health Outcomes of Female Trauma Survivors of Interpersonal Violence With Co-Occurring Disorders: A Randomized Controlled Trial. AB - This study was a randomized controlled trial that examined the impact of meditation practice on the mental health outcomes of female trauma survivors of interpersonal violence who have co-occurring disorders. Sixty-three female trauma survivors were randomly assigned to the meditation condition and the control condition. Treatment conditions consisted of a 6-week meditation curriculum that was influenced by Tibetan meditation tradition and focused on breathing, loving kindness, and compassion meditation. Clients in the meditation condition made significant changes in mental health symptoms ( t = 5.252, df = 31, p = .000) and trauma symptoms ( t = 6.009, df = 31, p = .000) from pre-treatment to post treatment, whereas non-significant changes were observed among the control condition clients. There were significant group differences between clients in the meditation condition and in the control condition on their mental health symptoms, F(1, 54) = 13.438, p = .001, and trauma symptoms, F(1, 54) = 13.395, p = .001, with a generally large effect size of eta squared .127 and .146, respectively. In addition, significantly more clients in the meditation condition achieved reliable change in mental health symptoms (35.5% vs. 8.3%) and trauma symptoms (42.3% vs. 4.8%) than clients in the control condition. Significance of the study is discussed with respect to the empirical evidence of meditation practice as a complementary behavioral intervention for treating female trauma survivors of interpersonal violence who have co-occurring disorders. PMID- 26149678 TI - Health Care Professionals as Victims of Stalking: Characteristics of the Stalking Campaign, Consequences, and Motivation in Italy. AB - Stalking is a phenomenon characterized by a set of repetitive behaviors, intrusive surveillance, control, communication, and search of contact with a victim who is afraid and/or worried and/or annoyed by such unwanted attention. Literature analysis shows that Health Care Professionals (HCPs) are at greater risk of being stalked than the general population. As described by Mullen, Pathe, Purcell, and Stuart, stalkers may have different motives: relational rejection, an infatuation, an inability to express their own emotions and recognize those of others, or a desire for revenge. The aim of this study was to explore stalkers' motivation as perceived by their victims, characteristics of stalking campaigns, and consequences. A copy of the Italian modified version of The Network for Surviving Stalking (NSS) Questionnaire on Stalking, the Beck Depression Inventory (BDI) and the State Trait Inventory (STAI) Y1-Y2 scales were distributed in six Italian state hospitals. Participants included 1,842 HCPs, 256 (13.9%) of which had been victims. The majority of victims reported that stalkers were Rejected (96, 37.5%), Intimacy seekers (41, 16%), Incompetent suitors (60, 23.4%), and/or Resentful (43, 16.8%; chi2 = 163.3, p = .001). Stalking campaigns were characterized by several behaviors, principally contact (by telephone calls, text message) and following. The stalking campaign caused in victims both physical and emotional consequences, the most frequent being weight changes, sleep disorders, weakness, apprehension, anger, and fear. The most used coping strategies were moving away and moving toward, the less used was moving inward. Intervention programs and preventive measures (both individual and organizational) for HCP victims and those who could be considered at risk are also discussed. PMID- 26149679 TI - Measuring Bystander Behavior in the Context of Sexual Violence Prevention: Lessons Learned and New Directions. AB - Bystander intervention is receiving increased attention as a potential sexual violence prevention strategy, especially to address campus sexual assault. Rather than focusing on potential perpetrators or victims, the bystander approach engages all members of a community to take action. A growing body of evaluative work demonstrates that bystander intervention education programs yield increased positive attitudes and behaviors related to sexual violence and greater willingness to intervene in pro-social ways. Future program outcome studies, however, would benefit from more refined measures of bystander action as it is a key variable that prevention education programs attempt to influence. The purpose of the current article is to present key issues, identified by four different research teams, on the measurement of bystander behavior related to sexual violence in the context of college campuses. Comparisons among the methods are made to suggest both lessons learned and new directions for bystander behavior measurement using self-report surveys in program evaluation. PMID- 26149680 TI - Periodontal disease, chronic kidney disease and mortality: results from the third National Health and Nutrition Examination Survey. AB - BACKGROUND: Periodontal disease is associated with increased mortality in the general population, however its prognostic significance in chronic kidney disease (CKD) is not known. We evaluated the joint effect of periodontal disease and CKD on all-cause and cardiovascular mortality. METHODS: Prospective observational study of 10,755 adult participants in the National Health and Nutrition Examination Survey, 1988-1994 (NHANES III). CKD was defined as estimated glomerular filtration rate < 60 ml/minute/1.73 m(2) or albumin-to-creatinine ratio >= 30 mg/g. Periodontal disease was defined as moderate (> 4 mm attachment loss in >= 2 mesial sites or 5 mm pocket depth in >= 2 mesial sites), or severe (> 6 mm attachment loss in >= 2 mesial sites and > 5 mm pocket depth in >= 1 mesial site). All-cause and cardiovascular mortality were evaluated using Cox proportional hazards models. RESULTS: There were 1,813 deaths over a median follow-up of 14 years. In multivariate analyses, as compared to participants with neither periodontal disease nor CKD, those with periodontal disease only or CKD only had increased all-cause mortality (HR 1.39; 95 % CI, 1.06-1.81 and 1.55; 1.30-1.84, respectively). The presence of both periodontal disease and CKD was associated with HR (95 % CI) 2.07 (1.65-2.59) for all-cause mortality, and 2.11 (1.52-2.94) for cardiovascular mortality. We found no evidence of multiplicativity or additivity between periodontal disease and CKD. In stratified analyses limited to individuals with CKD, periodontal disease (vs. not) was associated with adjusted HR (95 % CI) 1.35 (1.04-1.76) for all-cause, and 1.36 (0.95-1.95) for cardiovascular mortality. CONCLUSIONS: These findings confirm the well-established association between periodontal disease and increased mortality in the general population, and provide new evidence of this association among individuals with CKD. PMID- 26149681 TI - Can opportunities be enhanced for vaccinating children in home visiting programs? A population-based cohort study. AB - BACKGROUND: Home visiting programs focused on improving early childhood environments are commonplace in North America. A goal of many of these programs is to improve the overall health of children, including promotion of age appropriate vaccination. In this study, population-based data are used to examine the effect of a home visiting program on vaccination rates in children. METHODS: Home visiting program data from Manitoba, Canada were linked to several databases, including a provincial vaccination registry to examine vaccination rates in a cohort of children born between 2003 and 2009. Propensity score weights were used to balance potential confounders between a group of children enrolled in the program (n = 4,562) and those who were eligible but not enrolled (n = 5,184). Complete and partial vaccination rates for one and two year old children were compared between groups, including stratification into area-level income quintiles. RESULTS: Complete vaccination rates from birth to age 1 and 2 were higher for those enrolled in the Families First program [Average Treatment Effect Risk Ratio (ATE RR) 1.06 (95 % CI 1.03-1.08) and 1.10 (95 % CI 1.05-1.15) respectively]. No significant differences were found between groups having at least one vaccination at age 1 or 2 [ATE RR 1.01 (95 % CI 1.00-1.02) and 1.00 (95 % CI 1.00-1.01) respectively). The interaction between program and income quintiles was not statistically significant suggesting that the program effect did not differ by income quintile. CONCLUSIONS: Home visiting programs have the potential to increase vaccination rates for children enrolled, despite limited program content directed towards this end. Evidence-based program enhancements have the potential to increase these rates further, however more research is needed to inform policy makers of optimal approaches in this regard, especially with respect to cost-effectiveness. PMID- 26149682 TI - Association of relative telomere length with progression of chronic kidney disease in two cohorts: effect modification by smoking and diabetes. AB - Chronic kidney disease (CKD) is a highly progressive disease. We studied the association between relative telomere length (RTL) and CKD progression and tested whether this association is modified by smoking and diabetes mellitus. RTL was measured by qPCR in two prospective cohort studies, the MMKD-Study (n = 166) and the CRISIS-Study (n = 889) with a median follow-up of 4.5 and 2.8 years, respectively. Progression was defined as doubling of baseline serum creatinine (MMKD-Study) and/or end stage renal disease (both studies). 59 and 105 of the patients from MMKD and CRISIS experienced a progression of CKD. Mean standardized pooled RTL was 0.74 +/- 0.29. In the meta-analysis shorter RTL at baseline showed a borderline association with CKD progression (HR = 1.07 [95%CI 1.00-1.15]; p = 0.06). We observed an effect modification of RTL and CKD progression by smoking and diabetes (p-values of interaction p = 0.02 and p = 0.09, respectively). Each 0.1 unit shorter RTL was significantly associated with an increased hazard for CKD progression in active-smokers by 44% (HR = 1.44 [1.16-1.81]; p = 0.001) and in patients with diabetes mellitus by 16% (HR = 1.16 [1.01-1.34]; p = 0.03). Estimates were adjusted for baseline age, sex, proteinuria and GFR. This study in two independent cohorts reinforces that RTL is a marker and potentially a pathogenetic factor for CKD progression. PMID- 26149683 TI - Dimethylated H3K27 Is a Repressive Epigenetic Histone Mark in the Protist Entamoeba histolytica and Is Significantly Enriched in Genes Silenced via the RNAi Pathway. AB - RNA interference (RNAi) is a fundamental biological process that plays a crucial role in regulation of gene expression in many organisms. Transcriptional gene silencing (TGS) is one of the important nuclear roles of RNAi. Our previous data show that Entamoeba histolytica has a robust RNAi pathway that links to TGS via Argonaute 2-2 (Ago2-2) associated 27-nucleotide small RNAs with 5'-polyphosphate termini. Here, we report the first repressive histone mark to be identified in E. histolytica, dimethylation of H3K27 (H3K27Me2), and demonstrate that it is enriched at genes that are silenced by RNAi-mediated TGS. An RNAi-silencing trigger can induce H3K27Me2 deposits at both episomal and chromosomal loci, mediating gene silencing. Our data support two phases of RNAi-mediated TGS: an active silencing phase where the RNAi trigger is present and both H3K27Me2 and Ago2-2 concurrently enrich at chromosomal loci; and an established silencing phase in which the RNAi trigger is removed, but gene silencing with H3K27Me2 enrichment persist independently of Ago2-2 deposition. Importantly, some genes display resistance to chromosomal silencing despite induction of functional small RNAs. In those situations, the RNAi-triggering plasmid that is maintained episomally gets partially silenced and has H3K27Me2 enrichment, but the chromosomal copy displays no repressive histone enrichment. Our data are consistent with a model in which H3K27Me2 is a repressive histone modification, which is strongly associated with transcriptional repression. This is the first example of an epigenetic histone modification that functions to mediate RNAi mediated TGS in the deep-branching eukaryote E. histolytica. PMID- 26149684 TI - Interaction of Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 with Band 3 on Human Erythrocyte Surface Facilitates Parasite Growth. AB - Plasmodium tryptophan-rich proteins are involved in host-parasite interaction and thus potential drug/vaccine targets. Recently, we have described several P. vivax tryptophan-rich antigens (PvTRAgs), including merozoite expressed PvTRAg38, from this noncultivable human malaria parasite. PvTRAg38 is highly immunogenic in humans and binds to host erythrocytes, and this binding is inhibited by the patient sera. This binding is also affected if host erythrocytes were pretreated with chymotrypsin. Here, Band 3 has been identified as the chymotrypsin-sensitive erythrocyte receptor for this parasite protein. Interaction of PvTRAg38 with Band 3 has been mapped to its three different ectodomains (loops 1, 3, and 6) exposed at the surface of the erythrocyte. The binding region of PvTRAg38 to Band3 has been mapped to its sequence, KWVQWKNDKIRSWLSSEW, present at amino acid positions 197-214. The recombinant PvTRAg38 was able to inhibit the parasite growth in in vitro Plasmodium falciparum culture probably by competing with the ligand(s) of this heterologous parasite for the erythrocyte Band 3 receptor. In conclusion, the host-parasite interaction at the molecular level is much more complicated than known so far and should be considered during the development of anti malarial therapeutics. PMID- 26149685 TI - Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus. AB - Genome-wide association studies of inflammatory bowel diseases identified susceptible loci containing an autophagy-related gene. However, the role of autophagy in the colon, a major affected area in inflammatory bowel diseases, is not clear. Here, we show that colonic epithelial cell-specific autophagy-related gene 7 (Atg7) conditional knock-out (cKO) mice showed exacerbation of experimental colitis with more abundant bacterial invasion into the colonic epithelium. Quantitative PCR analysis revealed that cKO mice had abnormal microflora with an increase of some genera. Consistently, expression of antimicrobial or antiparasitic peptides such as angiogenin-4, Relmbeta, intelectin-1, and intelectin-2 as well as that of their inducer cytokines was significantly reduced in the cKO mice. Furthermore, secretion of colonic mucins that function as a mucosal barrier against bacterial invasion was also significantly diminished in cKO mice. Taken together, our results indicate that autophagy in colonic epithelial cells protects against colitis by the maintenance of normal gut microflora and secretion of mucus. PMID- 26149686 TI - The Solution Structure and Dynamics of Full-length Human Cerebral Dopamine Neurotrophic Factor and Its Neuroprotective Role against alpha-Synuclein Oligomers. AB - Cerebral dopamine neurotrophic factor (CDNF) is a promising therapeutic agent for Parkinson disease. As such, there has been great interest in studying its mode of action, which remains unknown. The three-dimensional crystal structure of the N terminus (residues 9-107) of CDNF has been determined, but there have been no published structural studies on the full-length protein due to proteolysis of its C-terminal domain, which is considered intrinsically disordered. An improved purification protocol enabled us to obtain active full-length CDNF and to determine its three-dimensional structure in solution. CDNF contains two well folded domains (residues 10-100 and 111-157) that are linked by a loop of intermediate flexibility. We identified two surface patches on the N-terminal domain that were characterized by increased conformational dynamics that should allow them to embrace active sites. One of these patches is formed by residues Ser-33, Leu-34, Ala-66, Lys-68, Ile-69, Leu-70, Ser-71, and Glu-72. The other includes a flexibly disordered N-terminal tail (residues 1-9), followed by the N terminal portion of alpha-helix 1 (residues Cys-11, Glu-12, Val-13, Lys-15, and Glu-16) and residue Glu-88. The surface of the C-terminal domain contains two conserved active sites, which have previously been identified in mesencephalic astrocyte-derived neurotrophic factor, a CDNF paralog, which corresponds to its intracellular mode of action. We also showed that CDNF was able to protect dopaminergic neurons against injury caused by alpha-synuclein oligomers. This advises its use against physiological damages caused by alpha-synuclein oligomers, as observed in Parkinson disease and several other neurodegenerative diseases. PMID- 26149687 TI - A Conserved Deubiquitinating Enzyme Uses Intrinsically Disordered Regions to Scaffold Multiple Protein Interaction Sites. AB - In the canonical view of protein function, it is generally accepted that the three-dimensional structure of a protein determines its function. However, the past decade has seen a dramatic growth in the identification of proteins with extensive intrinsically disordered regions (IDRs), which are conformationally plastic and do not appear to adopt single three-dimensional structures. One current paradigm for IDR function is that disorder enables IDRs to adopt multiple conformations, expanding the ability of a protein to interact with a wide variety of disparate proteins. The capacity for many interactions is an important feature of proteins that occupy the hubs of protein networks, in particular protein modifying enzymes that usually have a broad spectrum of substrates. One such protein modification is ubiquitination, where ubiquitin is attached to proteins through ubiquitin ligases (E3s) and removed through deubiquitinating enzymes. Numerous proteomic studies have found that thousands of proteins are dynamically regulated by cycles of ubiquitination and deubiquitination. Thus, how these enzymes target their wide array of substrates is of considerable importance for understanding the function of the cell's diverse ubiquitination networks. Here, we characterize a yeast deubiquitinating enzyme, Ubp10, that possesses IDRs flanking its catalytic protease domain. We show that Ubp10 possesses multiple, distinct binding modules within its IDRs that are necessary and sufficient for directing protein interactions important for Ubp10's known roles in gene silencing and ribosome biogenesis. The human homolog of Ubp10, USP36, also has IDRs flanking its catalytic domain, and these IDRs similarly contain binding modules important for protein interactions. This work highlights the significant protein interaction scaffolding abilities of IDRs in the regulation of dynamic protein ubiquitination. PMID- 26149688 TI - Loading of PAX3 to Mitotic Chromosomes Is Mediated by Arginine Methylation and Associated with Waardenburg Syndrome. AB - PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain. PAX3 WS mutants with mutations in homeodomain lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6. Mutant PAX3 proteins that lose mitotic chromosome localization block cell proliferation and normal development of zebrafish. These results reveal the molecular mechanism of PAX3s loading on mitotic chromosomes and the importance of this localization pattern in normal development. Our findings suggest that PAX3 WS mutants interfere with the normal functions of PAX3 in a dominant negative manner, which is important to the understanding of the pathogenesis of Waardenburg syndrome. PMID- 26149690 TI - Di-Ras2 Protein Forms a Complex with SmgGDS Protein in Brain Cytosol in Order to Be in a Low Affinity State for Guanine Nucleotides. AB - The Ras family of small GTPases function in a wide variety of biological processes as "molecular switches" by cycling between inactive GDP-bound and active GTP-bound forms. Di-Ras1 and Di-Ras2 were originally identified as small GTPases forming a distinct subgroup of the Ras family. Di-Ras1/Di-Ras2 mRNAs are detected predominantly in brain and heart tissues. Biochemical analysis of Di Ras1/Di-Ras2 has revealed that they have little GTPase activity and that their intrinsic guanine-nucleotide exchange rates are much faster than that of H-Ras. Yet little is known about the biological role(s) of Di-Ras1/Di-Ras2 or of how their activities are regulated. In the present study we found that endogenous Di Ras2 co-purifies with SmgGDS from rat brain cytosol. Size-exclusion chromatography of purified recombinant proteins showed that Di-Ras2 forms a high affinity complex with SmgGDS. SmgGDS is a guanine nucleotide exchange factor with multiple armadillo repeats and has recently been shown to specifically activate RhoA and RhoC. In contrast to the effect on RhoA, SmgGDS does not act as a guanine nucleotide exchange factor for Di-Ras2 but instead tightly associates with Di-Ras2 to reduce its binding affinity for guanine nucleotides. Finally, pulse-chase analysis revealed that Di-Ras2 binds, in a C-terminal CAAX motif dependent manner, to SmgGDS immediately after its synthesis. This leads to increased Di-Ras2 stability. We thus propose that isoprenylated Di-Ras2 forms a tight complex with SmgGDS in cytosol immediately after its synthesis, which lowers its affinity for guanine nucleotides. PMID- 26149689 TI - The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL. AB - The Fanconi Anemia (FA) DNA repair pathway is essential for the recognition and repair of DNA interstrand crosslinks (ICL). Inefficient repair of these ICL can lead to leukemia and bone marrow failure. A critical step in the pathway is the monoubiquitination of FANCD2 by the RING E3 ligase FANCL. FANCL comprises 3 domains, a RING domain that interacts with E2 conjugating enzymes, a central domain required for substrate interaction, and an N-terminal E2-like fold (ELF) domain. The ELF domain is found in all FANCL homologues, yet the function of the domain remains unknown. We report here that the ELF domain of FANCL is required to mediate a non-covalent interaction between FANCL and ubiquitin. The interaction involves the canonical Ile44 patch on ubiquitin, and a functionally conserved patch on FANCL. We show that the interaction is not necessary for the recognition of the core complex, it does not enhance the interaction between FANCL and Ube2T, and is not required for FANCD2 monoubiquitination in vitro. However, we demonstrate that the ELF domain is required to promote efficient DNA damage-induced FANCD2 monoubiquitination in vertebrate cells, suggesting an important function of ubiquitin binding by FANCL in vivo. PMID- 26149691 TI - Inhibition of Neisseria gonorrhoeae Type II Topoisomerases by the Novel Spiropyrimidinetrione AZD0914. AB - We characterized the inhibition of Neisseria gonorrhoeae type II topoisomerases gyrase and topoisomerase IV by AZD0914 (AZD0914 will be henceforth known as ETX0914 (Entasis Therapeutics)), a novel spiropyrimidinetrione antibacterial compound that is currently in clinical trials for treatment of drug-resistant gonorrhea. AZD0914 has potent bactericidal activity against N. gonorrhoeae, including multidrug-resistant strains and key Gram-positive, fastidious Gram negative, atypical, and anaerobic bacterial species (Huband, M. D., Bradford, P. A., Otterson, L. G., Basrab, G. S., Giacobe, R. A., Patey, S. A., Kutschke, A. C., Johnstone, M. R., Potter, M. E., Miller, P. F., and Mueller, J. P. (2014) In Vitro Antibacterial Activity of AZD0914: A New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-positive, Fastidious Gram-negative, and Atypical Bacteria. Antimicrob. Agents Chemother. 59, 467-474). AZD0914 inhibited DNA biosynthesis preferentially to other macromolecules in Escherichia coli and induced the SOS response to DNA damage in E. coli. AZD0914 stabilized the enzyme-DNA cleaved complex for N. gonorrhoeae gyrase and topoisomerase IV. The potency of AZD0914 for inhibition of supercoiling and the stabilization of cleaved complex by N. gonorrhoeae gyrase increased in a fluoroquinolone-resistant mutant enzyme. When a mutation, conferring mild resistance to AZD0914, was present in the fluoroquinolone resistant mutant, the potency of ciprofloxacin for inhibition of supercoiling and stabilization of cleaved complex was increased greater than 20-fold. In contrast to ciprofloxacin, religation of the cleaved DNA did not occur in the presence of AZD0914 upon removal of magnesium from the DNA-gyrase-inhibitor complex. AZD0914 had relatively low potency for inhibition of human type II topoisomerases alpha and beta. PMID- 26149693 TI - Folate receptor expression on murine and human adipose tissue macrophages. AB - OBJECTIVE AND DESIGN: Adipose tissue macrophages (ATMs) have been implicated in a number of obesity-related diseases. Because the activated macrophages associated with many types of autoimmune and inflammatory diseases express a folate receptor (FR) that can be exploited for FR-targeted drug delivery, we examined the visceral adipose tissue of obese mice and humans to determine whether ATMs also express FR that are accessible by folate conjugates. MATERIAL OR SUBJECTS: C57BL/6 or FATSO mice fed on either a low- or high-fat diet were used in murine studies. Human adipose tissue were obtained from healthy volunteers during adipose reduction surgery. METHODS: Visceral adipose tissue was collected from both obese mice and humans, collagenase digested, and stained with folate-Oregon Green and antibodies for macrophage markers including F4/80, mannose receptor (CD206), CD11b, and CD11c. Cells were then examined for expression of the above markers by flow cytometry. Furthermore, the ability of folate conjugates to target the FR-expressing ATMs in obese mice was evaluated in vivo. RESULTS: A subset of the ATMs harvested from obese mice were found to express FR. Subpopulations of ATMs also simultaneously express both pro- and anti inflammatory markers, and FR is expressed on both subsets. We then demonstrate that FR-expressing ATMs can be targeted with folate-linked fluorescent dyes in vivo. CONCLUSIONS: FR are expressed on multiple subsets of ATMs and these subsets can be targeted with folate-linked drugs, allowing for the possible development of FR-targeted therapies for obesity-related inflammatory diseases. PMID- 26149692 TI - Understanding the major risk factors in the beginning and the progression of rheumatoid arthritis: current scenario and future prospects. AB - Rheumatoid arthritis (RA), a chronic progressive inflammatory autoimmune disorder characterized by chronic pain and swelling primarily, affects the peripheral joints. RA had attained global concern in the last few decades, affecting more than 1.5 % of the world's population with higher female percentage than male. In the advanced stage, the disease is associated with the destruction of cartilage and bone along with a variety of systemic manifestations leading to functional disability. Inadequate early/preliminary diagnosis and non-specific therapeutics are the major challenges in the management of RA. Till date, the exact cause(s) of the disease remain(s) obscure, and several genetic, hormonal, and environmental factors are associated with the beginning and the progression of the disease. Rheumatoid factor is the only clinically approved bio-marker for the diagnosis, and RA is not restricted to bones, but also affects several vital organs in the advanced stages. Genome-wide association studies have explored novel genetic loci underlying common autoimmune diseases including RA. Recent discoveries of risk alleles have made it possible to define genetic risk profiles of patients with RA. The conventional non-steroidal anti-inflammatory drugs and steroidal drugs are still the choice for the treatment of RA under acute and chronic pathological conditions respectively. However, disease-modifying anti rheumatic drugs have shown remarkable success in the last decade. The present review provides a comprehensive understanding of the major risk factors and the molecular biology involved in the initiation and the progression of RA with a note on the recent trends in RA therapy. PMID- 26149695 TI - Eyeglasses-powered, contact lens-like platform with high power transfer efficiency. AB - We present a contact lens-like platform that is wirelessly powered by an external coil embedded in eyeglasses via magnetic resonance coupling at 13.56 MHz. The platform is composed of a transparent parylene film as a host substrate, an embedded spiral inductor as a power receiving coil, and metal interconnects for additional electronics. A multilayer thin-film parylene packaging process is used to meet the form factor of a contact lens. A 36 MUm-thick metal plating technique is employed on a parylene film to enhance the quality factor (Q) of the receiving coil (Q = 27.3 at 13.56 MHz). The power transfer method and techniques to compensate for coil misalignment are demonstrated on a pig eye, achieving a power transfer efficiency of 17.5 % at a 20-mm powering distance. The effect of tissue on the coil and the power transfer efficiency is examined. The high power transfer efficiency along with the wearable prototype demonstrated herein make promising progress toward smart contact lens in ocular diagnostics. PMID- 26149694 TI - Combined impacts of global changes on biodiversity across the USA. AB - Most studies of the effects of global changes on biodiversity focus on a single threat, but multiple threats lead to species extinction. We lack spatially explicit assessments of the intensity of multiple threats and their impacts on biodiversity. Here, we used a novel metric of cumulative threats and impacts to assess the consequences of multiple threats on 196 endemic species across the USA. We predict that large areas with high cumulative impact scores for amphibians, birds, mammals, and reptiles will be concentrated in the eastern part of the USA by the 2050 s and 2080 . These high cumulative impact values are due mainly to the presence of invasive species, climate change, cropland and pasture areas; additionally, a significant proportion of endemic species are vulnerable to some of these threats where they occur. This analysis provides a useful means of identifying where conservation measures and monitoring programs that should consider multiple threats should be implemented in the future. PMID- 26149696 TI - Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors. AB - We present a fully integrated implantable electrolysis-based micropump with incorporated EI dosing sensors. Wireless powering and data telemetry (through amplitude and frequency modulation) were utilized to achieve variable flow control and a bi-directional data link with the sensors. Wireless infusion rate control (0.14-1.04 MUL/min) and dose sensing (bolus resolution of 0.55-2 MUL) were each calibrated separately with the final circuit architecture and then simultaneous wireless flow control and dose sensing were demonstrated. Recombination detection using the dosing system, as well as, effects of coil separation distance and misalignment in wireless power and data transfer were studied. A custom-made normally closed spring-loaded ball check valve was designed and incorporated at the reservoir outlet to prevent backflow of fluids as a result of the reverse pressure gradient caused by recombination of electrolysis gases. Successful delivery, infusion rate control, and dose sensing were achieved in simulated brain tissue. PMID- 26149697 TI - Effect of TiO2 nanotubes arrays on osseointegration of orthodontic miniscrew. AB - To increase the stability of orthodontic miniscrews, TiO2 nanotube arrays were fabricated on the surface of Ti miniscrews and the effect of those arrays on the osseointegration of miniscrews was evaluated. Highly ordered TiO2 nanotube arrays were grown on the surface of orthodontic miniscrews. Ethylene glycol based electrolyte was used in the anodic oxidation process. Two-step anodic oxidation was conducted to obtain clean and open windows in TiO2 nanotube arrays. The diameter and length of the TiO2 nanotube arrays were ~ 70 nm and ~ 5 MUm, respectively. The miniscrews with TiO2 nanotube arrays were implanted in the legs of New Zealand white rabbits for 8 weeks. Histological osseointegration was assessed by bone-to-implant contact ratio, and three-dimensional bone volume ratio was measured by micro-computed tomography analysis. The miniscrews with TiO2 nanotube arrays had a greater mean bone-to-implant contact ratio of 52.8 % than the control, 29.3 %. Mean bone volume ratio (BV/TV) was also higher in the miniscrews with TiO2 nanotube arrays, at 81.2 % than those in the control via micro-CT analysis. Our findings support that TiO2 nanotube arrays on the surface of miniscrews enhance osseointegration and improve the stability of the miniscrew. PMID- 26149698 TI - Strongyloidiasis in immigrants and refugees in Canada. PMID- 26149699 TI - CMAJ Humanities adopts a second critical lens. PMID- 26149700 TI - A man with cardiac Lyme borreliosis. PMID- 26149701 TI - Doctors take lead in preparing for assisted dying law. PMID- 26149702 TI - Effect of older age on treatment decisions and outcomes among patients with traumatic spinal cord injury. AB - BACKGROUND: Older people are at increased risk of traumatic spinal cord injury from falls. We evaluated the impact of older age (>= 70 yr) on treatment decisions and outcomes. METHODS: We identified patients with traumatic spinal cord injury for whom consent and detailed data were available from among patients recruited (2004-2013) at any of the 31 acute care and rehabilitation hospitals participating in the Rick Hansen Spinal Cord Injury Registry. Patients were assessed by age group (< 70 v. >= 70 yr). The primary outcome was the rate of acute surgical treatment. We used bivariate and multivariate regression models to assess patient and injury-related factors associated with receiving surgical treatment and with the timing of surgery after arrival to a participating centre. RESULTS: Of the 1440 patients included in our study cohort, 167 (11.6%) were 70 years or older at the time of injury. Older patients were more likely than younger patients to be injured by falling (83.1% v. 37.4%; p < 0.001), to have a cervical injury (78.0% v. 61.6%; p = 0.001), to have less severe injuries on admission (American Spinal Injury Association Impairment Scale grade C or D: 70.5% v. 46.9%; p < 0.001), to have a longer stay in an acute care hospital (median 35 v. 28 d; p < 0.005) and to have a higher in-hospital mortality (4.2% v. 0.6%; p < 0.001). Multivariate analysis did not show that age of 70 years or more at injury was associated with a decreased likelihood of surgical treatment (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.22-1.07). An unplanned sensitivity analysis with different age thresholds showed that a threshold of 65 years was associated with a decreased chance of surgical treatment (OR 0.39, 95% CI 0.19-0.80). Older patients who underwent surgical treatment had a significantly longer wait time from admission to surgery than younger patients (37 v. 19 h; p < 0.001). INTERPRETATION: We found chronological age to be a factor influencing treatment decisions but not at the 70-year age threshold that we had hypothesized. Older patients waited longer for surgery and had a substantially higher in-hospital mortality despite having less severe injuries than younger patients. Further research into the link between treatment delays and outcomes among older patients could inform surgical guideline development. PMID- 26149703 TI - How to make opinion leaders and influence people. PMID- 26149705 TI - Should HPV vaccination be gender neutral? PMID- 26149706 TI - Fluorinated chemicals need stricter control. PMID- 26149708 TI - Trial registration 10 years on. PMID- 26149707 TI - A High Throughput Micro-Chamber Array Device for Single Cell Clonal Cultivation and Tumor Heterogeneity Analysis. AB - Recently, single cell cloning techniques have been gradually developed benefited from their important roles in monoclonal antibody screening, tumor heterogeneity research fields, etc. In this study, we developed a high throughput device containing 1400 lateral chambers to efficiently isolate single cells and carry out long-term single cell clonal cultivation as well as tumor heterogeneity studies. Most of the isolated single cells could proliferate normally nearly as long as three weeks and hundreds of clones could be formed once with one device, which made it possible to study tumor heterogeneity at single cell level. The device was further used to examine tumor heterogeneity such as morphology, growth rate, anti-cancer drug tolerance as well as adenosine triphosphate-binding cassette (ABC) transporter ABCG2 protein expression level. Except for the single cell isolation and tumor heterogeneity studies, the device is expected to be used as an excellent platform for drug screening, tumor biomarker discovering and tumor metastasis assay. PMID- 26149709 TI - Incidental diagnosis of cardiac myxoma by EUS. PMID- 26149710 TI - Severe spruelike enteropathy associated with olmesartan observed by double balloon enteroscopy. PMID- 26149711 TI - Microcirculatory dysfunction and tissue oxygenation in critical illness. AB - Severe sepsis is defined by organ failure, often of the kidneys, heart, and brain. It has been proposed that inadequate delivery of oxygen, or insufficient extraction of oxygen in tissue, may explain organ failure. Despite adequate maintenance of systemic oxygen delivery in septic patients, their morbidity and mortality remain high. The assumption that tissue oxygenation can be preserved by maintaining its blood supply follows from physiological models that only apply to tissue with uniformly perfused capillaries. In sepsis, the microcirculation is profoundly disturbed, and the blood supply of individual organs may therefore no longer reflect their access to oxygen. We review how capillary flow patterns affect oxygen extraction efficacy in tissue, and how the regulation of tissue blood flow must be adjusted to meet the metabolic needs of the tissue as capillary flows become disturbed as observed in critical illness. Using the brain, heart, and kidney as examples, we discuss whether disturbed capillary flow patterns might explain the apparent mismatch between organ blood flow and organ function in sepsis. Finally, we discuss diagnostic means of detecting capillary flow disturbance in animal models and in critically ill patients, and address therapeutic strategies that might improve tissue oxygenation by modifying capillary flow patterns. PMID- 26149712 TI - Pomalidomide and Low-Dose Dexamethasone Improves Health-Related Quality of Life and Prolongs Time to Worsening in Relapsed/Refractory Patients With Multiple Myeloma Enrolled in the MM-003 Randomized Phase III Trial. AB - BACKGROUND: Health-related quality of life (HRQoL) is an important element for consideration in treatment decisions in patients with relapsed/refractory multiple myeloma (RRMM). The pivotal MM-003 (A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone vs. High-Dose Dexamethasone in Patients With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study [NIMBUS]) randomized, open-label, multicenter, phase III trial demonstrated improved progression-free survival (PFS) and prolonged overall survival (OS) with pomalidomide (POM) plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in patients with RRMM in whom lenalidomide (LEN) and bortezomib (BORT) had failed. MM-003 also investigated HRQoL as a predefined secondary end point. PATIENTS AND METHODS: Recruited patients (n = 455) were refractory to their last treatment and had failed LEN and BORT after >= 2 consecutive cycles of each (alone or in combination). Eight clinically relevant and validated HRQoL domains from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-MY20, and EQ-5D questionnaires were selected for analysis. Time to symptom worsening based on minimally important differences (MIDs) was calculated. RESULTS: Clinically meaningful improvements in HRQoL as determined by MIDs, regression analyses, and best response analyses were observed more frequently in patients receiving POM + LoDEX than in those receiving HiDEX. POM + LoDEX significantly extended median time to clinically meaningful worsening in HRQoL versus HiDEX in 4 HRQoL domains and demonstrated a trend in an additional 3 domains. Patients in the HiDEX arm experienced earlier HRQoL deterioration compared with those in the POM + LoDEX arm in each domain analyzed. CONCLUSION: POM + LoDEX offer good clinical outcomes that lead to improved and prolonged HRQoL compared with HiDEX in patients with RRMM and end-stage disease. PMID- 26149715 TI - Chromatin: Histone influences on chromosomal translocations. PMID- 26149716 TI - Molecular evolution: Warm and wild lizard sex changes. PMID- 26149714 TI - Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms. AB - Drug therapy has a crucial role in the treatment of viral, bacterial, fungal and protozoan infections, as well as the control of human cancer. The success of therapy is being threatened by the increasing prevalence of resistance. We examine and compare mechanisms of drug resistance in these diverse biological systems (using HIV and Plasmodium falciparum as examples of viral and protozoan pathogens, respectively) and discuss how factors - such as mutation rates, fitness effects of resistance, epistasis and clonal interference - influence the evolutionary trajectories of drug-resistant clones. We describe commonalities and differences related to resistance development that could guide strategies to improve therapeutic effectiveness and the development of a new generation of drugs. PMID- 26149713 TI - Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders. AB - Genetic and genomic approaches have implicated hundreds of genetic loci in neurodevelopmental disorders and neurodegeneration, but mechanistic understanding continues to lag behind the pace of gene discovery. Understanding the role of specific genetic variants in the brain involves dissecting a functional hierarchy that encompasses molecular pathways, diverse cell types, neural circuits and, ultimately, cognition and behaviour. With a focus on transcriptomics, this Review discusses how high-throughput molecular, integrative and network approaches inform disease biology by placing human genetics in a molecular systems and neurobiological context. We provide a framework for interpreting network biology studies and leveraging big genomics data sets in neurobiology. PMID- 26149718 TI - Comparisons of cell culture medium using distribution of morphological features in microdevice. AB - As the number of available cell types grows, it becomes necessary to develop more effective ways to optimize the cell-culture medium for each cell line and culture condition. However, because of the vast number of parameters that must be decided, such as the combination of components, optimization is both laborious and costly. Microdevices are a cost-effective way to perform such evaluations because they use only a small volume of media and enable high-throughput analyses. However, assays performed in microdevices are themselves minimized, and each assay unit (well/chamber) commonly contains an insufficient number of cells for comprehensive evaluations such as gene-expression or flow-cytometry analyses. To address this issue, we introduced image-based analysis in conjunction with microdevice assays; this approach allows quantification of every cell in each assay unit. To quantitatively profile differences in cellular behaviors in a microdevice under different culture media conditions, we developed a non-staining image-based analysis method that utilizes cellular morphology. Our approach combines the structural advantages of microdevices, which can increase the stability of images, and the quantitative advantages of an image-based cell evaluation technique that utilizes time-course population change in several morphological features. Our results demonstrate that cellular changes due to small alterations in the concentration of serum in medium or differences in the basal medium can be profiled using only microscopic images. PMID- 26149719 TI - Impact of zinc supplementation on the improved fructose/xylose utilization and butanol production during acetone-butanol-ethanol fermentation. AB - Lignocellulosic biomass and dedicated energy crops such as Jerusalem artichoke are promising alternatives for biobutanol production by solventogenic clostridia. However, fermentable sugars such as fructose or xylose released from the hydrolysis of these feedstocks were subjected to the incomplete utilization by the strains, leading to relatively low butanol production and productivity. When 0.001 g/L ZnSO4.7H2O was supplemented into the medium containing fructose as sole carbon source, 12.8 g/L of butanol was achieved with butanol productivity of 0.089 g/L/h compared to only 4.5 g/L of butanol produced with butanol productivity of 0.028 g/L/h in the control without zinc supplementation. Micronutrient zinc also led to the improved butanol production up to 8.3 g/L derived from 45.2 g/L xylose as sole carbon source with increasing butanol productivity by 31.7%. Moreover, the decreased acids production was observed under the zinc supplementation condition, resulting in the increased butanol yields of 0.202 g/g-fructose and 0.184 g/g-xylose, respectively. Similar improvements were also observed with increasing butanol production by 130.2 % and 8.5 %, butanol productivity by 203.4% and 18.4%, respectively, in acetone-butanol ethanol fermentations from sugar mixtures of fructose/glucose (4:1) and xylose/glucose (1:2) simulating the hydrolysates of Jerusalem artichoke tubers and corn stover. The results obtained from transcriptional analysis revealed that zinc may have regulatory mechanisms for the sugar transport and metabolism of Clostridium acetobutylicum L7. Therefore, micronutrient zinc supplementation could be an effective way for economic development of butanol production derived from these low-cost agricultural feedstocks. PMID- 26149720 TI - Comparative metabolic responses and adaptive strategies of wheat (Triticum aestivum) to salt and alkali stress. AB - BACKGROUND: It is well known that salinization (high-pH) has been considered as a major environmental threat to agricultural systems. The aim of this study was to investigate the differences between salt stress and alkali stress in metabolic profiles and nutrient accumulation of wheat; these parameters were also evaluated to determine the physiological adaptive mechanisms by which wheat tolerates alkali stress. RESULTS: The harmful effect of alkali stress on the growth and photosynthesis of wheat were stronger than those of salt stress. High-pH of alkali stress induced the most of phosphate and metal ions to precipitate; as a result, the availability of nutrients significantly declined. Under alkali stress, Ca sharply increased in roots, however, it decreased under salt stress. In addition, we detected the 75 metabolites that were different among the treatments according to GC-MS analysis, including organic acids, amino acids, sugars/polyols and others. The metabolic data showed salt stress and alkali stress caused different metabolic shifts; alkali stress has a stronger injurious effect on the distribution and accumulation of metabolites than salt stress. These outcomes correspond to specific detrimental effects of a highly pH environment. CONCLUSIONS: Ca had a significant positive correlation with alkali tolerates, and increasing Ca concentration can immediately trigger SOS Na exclusion system and reduce the Na injury. Salt stress caused metabolic shifts toward gluconeogenesis with increased sugars to avoid osmotic stress; energy in roots and active synthesis in leaves were needed by wheat to develop salt tolerance. Alkali stress (at high pH) significantly inhibited photosynthetic rate; thus, sugar production was reduced, N metabolism was limited, amino acid production was reduced, and glycolysis was inhibited. PMID- 26149717 TI - Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials. AB - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. OBJECTIVES: To determine the 16-week efficacy and safety of two oral tofacitinib doses vs. placebo in patients with moderate-to-severe chronic plaque psoriasis. METHODS: Patients in two similarly designed phase III studies (OPT Pivotal 1, NCT01276639, n = 901; OPT Pivotal 2, NCT01309737, n = 960) were initially randomized 2 : 2 : 1 to tofacitinib 10 or 5 mg or placebo, twice daily. Coprimary efficacy end points (week 16) included the proportion of patients achieving Physician's Global Assessment (PGA) of 'clear' or 'almost clear' (PGA response) and the proportion achieving >= 75% reduction in Psoriasis Area and Severity Index (PASI 75). RESULTS: Across OPT Pivotal 1 and OPT Pivotal 2, 745 patients received tofacitinib 5 mg, 741 received tofacitinib 10 mg and 373 received placebo. At week 16, a greater proportion of patients achieved PGA responses with tofacitinib 5 and 10 mg twice daily vs. placebo (OPT Pivotal 1, 41.9% and 59.2% vs. 9.0%; OPT Pivotal 2, 46.0% and 59.1% vs. 10.9%; all P < 0.001). Higher PASI 75 rates were observed with tofacitinib vs. placebo (OPT Pivotal 1, 39.9%, 59.2% and 6.2%, respectively, for tofacitinib 5 and 10 mg twice daily and placebo; OPT Pivotal 2, 46.0%, 59.6% and 11.4%; all P < 0.001 vs. placebo). Adverse event (AE) rates appeared generally similar across groups; rates of serious AEs, infections, malignancies and discontinuations due to AEs were low. Twelve patients reported herpes zoster across the tofacitinib treatment groups in both studies vs. none in the respective placebo groups. The most common AE across groups was nasopharyngitis. CONCLUSIONS: Oral tofacitinib demonstrated significant efficacy vs. placebo during the initial 16 weeks of treatment in patients with moderate-to-severe psoriasis. Safety findings were consistent with prior studies. PMID- 26149721 TI - A G-quadruplex-binding macrodomain within the "SARS-unique domain" is essential for the activity of the SARS-coronavirus replication-transcription complex. AB - The multi-domain non-structural protein 3 of SARS-coronavirus is a component of the viral replication/transcription complex (RTC). Among other domains, it contains three sequentially arranged macrodomains: the X domain and subdomains SUD-N as well as SUD-M within the "SARS-unique domain". The X domain was proposed to be an ADP-ribose-1"-phosphatase or a poly(ADP-ribose)-binding protein, whereas SUD-NM binds oligo(G)-nucleotides capable of forming G-quadruplexes. Here, we describe the application of a reverse genetic approach to assess the importance of these macrodomains for the activity of the SARS-CoV RTC. To this end, Renilla luciferase-encoding SARS-CoV replicons with selectively deleted macrodomains were constructed and their ability to modulate the RTC activity was examined. While the SUD-N and the X domains were found to be dispensable, the SUD-M domain was crucial for viral genome replication/transcription. Moreover, alanine replacement of charged amino-acid residues of the SUD-M domain, which are likely involved in G-quadruplex-binding, caused abrogation of RTC activity. PMID- 26149723 TI - Net effects of multiple stressors in freshwater ecosystems: a meta-analysis. AB - The accelerating rate of global change has focused attention on the cumulative impacts of novel and extreme environmental changes (i.e. stressors), especially in marine ecosystems. As integrators of local catchment and regional processes, freshwater ecosystems are also ranked highly sensitive to the net effects of multiple stressors, yet there has not been a large-scale quantitative synthesis. We analysed data from 88 papers including 286 responses of freshwater ecosystems to paired stressors and discovered that overall, their cumulative mean effect size was less than the sum of their single effects (i.e. an antagonistic interaction). Net effects of dual stressors on diversity and functional performance response metrics were additive and antagonistic, respectively. Across individual studies, a simple vote-counting method revealed that the net effects of stressor pairs were frequently more antagonistic (41%) than synergistic (28%), additive (16%) or reversed (15%). Here, we define a reversal as occurring when the net impact of two stressors is in the opposite direction (negative or positive) from that of the sum of their single effects. While warming paired with nutrification resulted in additive net effects, the overall mean net effect of warming combined with a second stressor was antagonistic. Most importantly, the mean net effects across all stressor pairs and response metrics were consistently antagonistic or additive, contrasting the greater prevalence of reported synergies in marine systems. Here, a possible explanation for more antagonistic responses by freshwater biota to stressors is that the inherent greater environmental variability of smaller aquatic ecosystems fosters greater potential for acclimation and co-adaptation to multiple stressors. PMID- 26149722 TI - A combination SMS and transportation reimbursement intervention to improve HIV care following abnormal CD4 test results in rural Uganda: a prospective observational cohort study. AB - BACKGROUND: Up to 50 % of HIV-infected persons in sub-Saharan Africa are lost from care between HIV diagnosis and antiretroviral therapy (ART) initiation. Structural barriers, including cost of transportation to clinic and poor communication systems, are major contributors. METHODS: We conducted a prospective, pragmatic, before-and-after clinical trial to evaluate a combination mobile health and transportation reimbursement intervention to improve care at a publicly operated HIV clinic in Uganda. Patients undergoing CD4 count testing were enrolled, and clinicians selected a result threshold that would prompt early return for ART initiation or further care. Participants enrolled in the pre intervention period (January - August 2012) served as a control group. Participants in the intervention period (September 2012 - November 2013) were randomized to receive daily short message service (SMS) messages for up to seven days in one of three formats: 1) messages reporting an abnormal result directly, 2) personal identification number-protected messages reporting an abnormal result, or 3) messages reading "ABCDEFG" to confidentially convey an abnormal result. Participants returning within seven days of their first message received transportation reimbursements (about $6USD). Our primary outcomes of interest were time to return to clinic and time to ART initiation. RESULTS: There were 45 participants in the pre-intervention period and 138 participants in the intervention period (46, 49, and 43 in the direct, PIN, and coded groups, respectively) with low CD4 count results. Median time to clinic return was 33 days (IQR 11-49) in the pre-intervention period and 6 days (IQR 3-16) in the intervention period (P < 0.001); and median time to ART initiation was 47 days (IQR 11-75) versus 12 days (IQR 5-19), (P < 0.001). In multivariable models, participants in the intervention period had earlier return to clinic (AHR 2.32, 95 %CI 1.53 to 3.51) and earlier time to ART initiation (AHR 2.27, 95 %CI 1.38 to 3.72). All three randomized message formats improved time to return to clinic and time to ART initiation (P < 0.01 for all comparisons versus the pre-intervention period). CONCLUSIONS: A combination of an SMS laboratory result communication system and transportation reimbursements significantly decreased time to clinic return and time to ART initiation after abnormal CD4 test results. TRIAL REGISTRATIONS: Clinicaltrials.gov NCT01579214 , approved 13 April 2012. PMID- 26149724 TI - Near Infrared Imaging of Indocyanine Green Distribution in Pregnant Mice and Effects of Concomitant Medications. AB - The transfer of indocyanine green (ICG) across the placenta is considered to be very low based on measurements in fetal blood. The goal of this study was to evaluate in mice ICG's distribution within fetuses themselves and effects of concomitant medications on fetal exposure. Mid-gestational (day 12.5) and late gestational (day 17.5) age mice were imaged after administration of ICG (0.167 mg), in the presence and the absence of the organic anion transporting polypeptide (OATP) inhibitor rifampin (10 mg/kg, n = 11, or 20 mg/kg, n = 1) or the P-glycoprotein inhibitor valspodar (12.5 mg/kg). In vivo ICG emission intensity was followed by ex vivo analysis of blood and tissue emission. Both valspodar and rifampin increased ICG's emission intensity within maternal tissues. In addition, valspodar enhanced the ex vivo signal in mid-pregnancy placentae (2.1-fold; p < 0.01) and fetuses (2.4-fold; p < 0.01), and reduced late pregnancy placenta:blood and fetus:blood ratios. Rifampin increased placental (1.4-fold, p < 0.05, and 2.3-fold, p < 0.01, in mid- and late-pregnancy, respectively) and fetal (2.2-fold, p < 0.01, and 3.2-fold, p < 0.01, in mid- and late-pregnancy) ICG signal. Similarly to valspodar, late-pregnancy placenta:blood and fetus:blood ratios were reduced by rifampin. Both inhibitors enhanced ICG's emission in fetal leg, liver, and brain. In conclusion, ICG distribution into the mouse fetus can be enhanced when used concomitantly with OATP or P-glycoprotein inhibitors. The greater distribution within individual fetal tissues is likely related to ICG's greater transplacental transfer. Until further data are available on ICG's safety when combined with medications that affect its maternal handling, such combinations should be used with caution. PMID- 26149725 TI - Re: Regional Geographic Variations in Kidney Cancer Incidence Rates in European Countries. PMID- 26149726 TI - Re: Phase 2 Trial of Neoadjuvant Axitinib in Patients with Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma. PMID- 26149727 TI - Re: Genomic Classifier Identifies Men with Adverse Pathology After Radical Prostatectomy Who Benefit from Adjuvant Radiation Therapy. PMID- 26149728 TI - Re: Clinical Outcome of Cloacal Exstrophy, Current Status, and a Change in Surgical Management. PMID- 26149729 TI - Re: Drug Adherence and Clinical Outcomes for Patients Under Pharmacological Therapy for Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia: Population-based Cohort Study. PMID- 26149730 TI - Re: Disease Control Outcomes from Analysis of Pooled Individual Patient Data from Five Comparative Randomized Clinical Trials of Degarelix Versus Luteinising Hormone-releasing Hormone Agonists. PMID- 26149731 TI - Corrigendum to "Incidence of Prostate Cancer After Termination of Screening in a Population-based Randomised Screening Trial" [Eur Urol 2013;64:703-9]. PMID- 26149733 TI - The association of intrafamilial violence against children with symptoms of atopic and non-atopic asthma: A cross-sectional study in Salvador, Brazil. AB - This study aims to describe the types of intrafamilial violence perpetrated against children according to living conditions, family factors, and child characteristics, and to identify the association between types of intrafamilial violence and asthma symptoms in atopic and non-atopic children. A cross-sectional study was carried out with 1,370 caregivers as part of the Social Changes, Asthma and Allergy in Latin America (SCAALA) study, conducted in 2006 in Brazil. The study population was selected by random sampling. The main outcome measures were atopic and non-atopic asthma. We investigate the association between intrafamilial violence and asthma symptoms in atopic and non-atopic children. A backward multivariate logistic polytomous regression was performed to verify the main association. Nonviolent discipline (NVD) and maltreatment nonviolent discipline (MNVD) were positively associated with non-atopic asthma symptoms (NVD: odds ratio (OR)=1.95/95% confidence interval (CI)=1.17-3.25; MNVD: OR=1.95/95% CI=1.19-3.20). However, for the most severe intrafamilial violence, this association was not found after control of potential confounders. This study demonstrates the effect of types of intrafamilial violence on non-atopic asthma. Intrafamilial violence against children represents one more component in the determination of non-atopic asthma in Latin America. PMID- 26149734 TI - Behavioral and central correlates of contextual fear learning and contextual modulation of cued fear in posttraumatic stress disorder. AB - Patients with posttraumatic stress disorder (PTSD) show persistent fear responses to trauma cues in contexts in which these cues no longer predict danger. This might be related to deficient context and enhanced cue conditioning. To test this hypothesis, we examined context conditioning directly followed by a cue conditioning phase against the background of the previously conditioned context in 12 patients with PTSD, 14 traumatized control subjects without PTSD and 11 matched never-traumatized controls. We used differential context and cue conditioning paradigms, with rooms as contexts and geometric figures as cues, and assessed valence, arousal and contingency ratings as well as brain responses using functional magnetic resonance imaging. The PTSD patients showed more hippocampal activation and differentiated the threat and safe contexts less in their contingency ratings than the healthy controls during context acquisition. In the subsequent cue acquisition against the background of the conditioned context, they displayed similar threat versus safe cue differentiation in contingency ratings as the two control groups. Moreover, PTSD patients failed to extinguish the differential conditioned context and cued fear responses and showed increased fear to both the dangerous and the safe conditioned contexts and cues in some ratings. This study provides evidence for a dissociation of brain responses and contingency awareness in PTSD which represents impaired context learning and a deficient contextual modulation of cue-related associations. In addition, extinction and extinction recall were impaired in PTSD. These changes were related to PTSD symptoms and suggest that contextual learning deficits may contribute to PTSD. PMID- 26149735 TI - Genetic screening reveals a link between Wnt signaling and antitubulin drugs. AB - The antitubulin drugs, paclitaxel (PX) and colchicine (COL), inhibit cell growth and are therapeutically valuable. PX stabilizes microtubules, while COL promotes their depolymerization. But, the drug concentrations that alter tubulin polymerization are hundreds of times higher than their clinically useful levels. To map genetic targets for drug action at single-gene resolution, we used a human radiation hybrid panel. We identified loci that affected cell survival in the presence of five compounds of medical relevance. For PX and COL, the zinc and ring finger 3 (ZNRF3) gene dominated the genetic landscape at therapeutic concentrations. ZNRF3 encodes an R-spondin regulated receptor that inhibits Wingless/Int (Wnt) signaling. Overexpression of the ZNRF3 gene shielded cells from antitubulin drug action, while small interfering RNA knockdowns resulted in sensitization. Further a potent pharmacological inhibitor of Wnt signaling, Wnt C59, protected cells from PX and COL. Our results suggest that the antitubulin drugs perturb microtubule dynamics, thereby influencing Wnt signaling. PMID- 26149736 TI - The -308 TNFalpha and the -174 IL-6 promoter polymorphisms associate with effective anti-TNFalpha treatment in seronegative spondyloarthritis. AB - The genetic predisposition to a long-term efficacy of anti-tumor necrosis factor (TNF)alpha treatment in seronegative spondyloarthritis (SpA) was investigated by analysing the possible correlation between several single nucleotide gene polymorphisms and the retention rate of anti-TNFalpha therapies. We compared patients needing to switch the first anti-TNFalpha (Sw, No. 64) within at least 12 months of follow-up with patients not needing to switch (NSw, No. 123), observing at least 6 months of treatment to establish anti-TNFalpha failure, leading to treatment change. Response to treatment was evaluated by standardised criteria (BASDAI for axial involvement, DAS28-EULAR for peripheral involvement). The TNFalpha -308 A allele and the interleukin (IL)-6 -174GG homozygosis resulted as independent biomarkers predicting survival of the first anti-TNFalpha therapy in SpA patients (P=0.007, odds ratio (OR): 4.4, 95% confidence interval (CI)=1.5 13.1 and P=0.035, OR: 2.1, 95% CI=1.1-4.4). Also, the male gender (P=0.001, OR: 3.4, 95% CI=1.6-7.1) associated with the NSw phenotype, whereas no association was found either with the specific diagnosis or the predominant joint involvement. PMID- 26149737 TI - Meta-analysis reveals significant association of 3'-UTR VNTR in SLC6A3 with smoking cessation in Caucasian populations. AB - Many studies have examined the association between SLC6A3 3'-untranslated region (UTR) variable number tandem repeat (VNTR) polymorphism and smoking cessation; however, the results are inconclusive, primarily because of the small-to-moderate size samples. The primary goal of this study was to determine whether this polymorphism has any effect on smoking cessation by a meta-analysis of all reported studies. We adopted a 9-repeat dominant model that considers 9-repeat and non-9-repeat as two genotypes and compared their frequencies in former vs current smokers. Eleven studies with 5480 participants were included. Considering the presence of study heterogeneity and differences in the availability of information from each study, three separate meta-analyses were performed with the Comprehensive Meta-Analysis statistical software (version 2.0). The first meta analysis provided evidence of association between the 9-repeat genotype and smoking cessation under the fixed-effects model (pooled odds ratio (OR)=1.13; 95% confidence interval (CI)=1.01, 1.27; P=0.037) but not in the random-effects model (pooled OR=1.11; 95% CI=0.96, 1.29; P=0.159). Given the marginal evidence of heterogeneity among studies (P=0.10; I2=35.9%), which likely was caused by inclusion of an Asian population treatment study with an opposite effect of the polymorphism on smoking cessation, we excluded the data of this study, revealing a significant association between the 9-repeat genotype and smoking cessation under both the fixed- and random-effects models (pooled OR=1.15; 95% CI=1.02, 1.29; P=0.02 for both models). By analyzing adjusted and unadjusted results, we performed the third meta-analysis, which showed consistently that the 9-repeat genotype was significantly associated with smoking cessation under both the fixed and random-effects models (pooled OR=1.17; 95% CI=1.04, 1.31; P=0.009 for both models). We conclude that the 3'-UTR VNTR polymorphism is significantly associated with smoking cessation, and smokers with one or more 9-repeat alleles have a 17% higher probability of smoking cessation than smokers carrying no such allele. PMID- 26149738 TI - Pharmacogenomic variants have larger effect sizes than genetic variants associated with other dichotomous complex traits. AB - It has been suggested that pharmacogenomic phenotypes are influenced by genetic variants with larger effect sizes than other phenotypes, such as complex disease risk. This is presumed to reflect the fact that relevant environmental factors (drug exposure) are appropriately measured and taken into account. To test this hypothesis, we performed a systematic comparison of effect sizes between pharmacogenomic and non-pharmacogenomic phenotypes across all genome-wide association studies (GWAS) reported in the NHGRI GWAS catalog. We found significantly larger effect sizes for studies focused on pharmacogenomic phenotypes, as compared with complex disease risk, morphological phenotypes and endophenotypes. We found no significant differences in effect sizes between pharmacogenomic studies focused on adverse events versus those focused on drug efficacy. Furthermore, we found that this pattern persists among sample size matched studies, suggesting that this pattern does not reflect overestimation of effect sizes due to smaller sample sizes in pharmacogenomic studies.The Pharmacogenomics Journal advance online publication, 7 July 2015; doi:10.1038/tpj.2015.47. PMID- 26149745 TI - Multiple Approaches for Increasing the Immunogenicity of an Epitope-Based Anti HIV Vaccine. AB - The development of a highly effective vaccine against the human immunodeficiency virus (HIV) will likely be based on rational vaccine design, since traditional vaccine approaches have failed so far. In recent years, an understanding of what type of immune response is protective against infection and/or disease facilitated vaccine design. T cell-based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. In this context, CD4(+) T cells play a direct cytotoxic role and are also important for the generation and maintenance of functional CD8(+) T and B cell responses. The use of MHC-binding algorithms has allowed the identification of novel CD4(+) T cell epitopes that could be used in vaccine design, the so-called epitope-driven vaccine design. Epitope-based vaccines have the ability to focus the immune response on highly antigenic, conserved epitopes that are fully recognized by the target population. We have recently mapped a set of conserved multiple HLA-DR-binding HIV-1 CD4 epitopes and observed interferon (IFN)-gamma-producing CD4(+) T cells when we tested these peptides in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals. We then designed multiepitopic DNA vaccines that induced broad and polyfunctional T cell responses in immunized mice. In this review we will focus on alternative strategies to increase the immunogenicity of an epitope-based vaccine against HIV infection. PMID- 26149746 TI - Experimental fertilization increases amino acid content in floral nectar, fruit set and degree of selfing in the orchid Gymnadenia conopsea. AB - Floral traits have evolved to maximize reproductive success by attracting pollinators and facilitating pollination. Highly attractive floral traits may, however, also increase the degree of self-pollination, which could become detrimental for plant fitness through inbreeding depression. Floral nectar is a trait that is known to strongly mediate pollinator attraction and plant reproductive success, but the particular role of the nectar amino acid (AA) composition is poorly understood. Therefore, we experimentally manipulated the nectar AA composition and abundance of the Lepidoptera-pollinated orchid Gymnadenia conopsea through soil fertilization, and we quantified AA content and AA composition through high performance anion exchange chromatography with pulsed amperometric detection. Mixed models were then used to evaluate differences in pollinia removal, fruit set, seed set and degree of selfing between fertilized and control individuals. Selfing rates were estimated using microsatellite markers. We found that fertilized individuals had a significantly higher nectar AA content and an altered AA composition, whereas plant height, number of flowers, nectar volume and sugar concentration remained unchanged. Fertilized individuals also had significantly more pollinia removed and a higher fruit set, whereas control plants that did not receive the fertilization treatment had significantly fewer selfed seeds, and more viable seeds. Although we cannot exclude a role of changes in floral scent following the fertilization treatment, our results strongly suggest a relation among nectar AA composition, fruiting success and selfing rates. Our results also indicate potential consequences of nutrient pollution for plant reproductive success, through the induced changes in nectar AA composition. PMID- 26149747 TI - Towards self-assembled hybrid artificial cells: novel bottom-up approaches to functional synthetic membranes. AB - There has been increasing interest in utilizing bottom-up approaches to develop synthetic cells. A popular methodology is the integration of functionalized synthetic membranes with biological systems, producing "hybrid" artificial cells. This Concept article covers recent advances and the current state-of-the-art of such hybrid systems. Specifically, we describe minimal supramolecular constructs that faithfully mimic the structure and/or function of living cells, often by controlling the assembly of highly ordered membrane architectures with defined functionality. These studies give us a deeper understanding of the nature of living systems, bring new insights into the origin of cellular life, and provide novel synthetic chassis for advancing synthetic biology. PMID- 26149748 TI - Sterile Filtration of Highly Concentrated Protein Formulations: Impact of Protein Concentration, Formulation Composition, and Filter Material. AB - Differences in filtration behavior of concentrated protein formulations were observed during aseptic drug product manufacturing of biologics dependent on formulation composition. The present study investigates filtration forces of monoclonal antibody formulations in a small-scale set-up using polyvinylidene difluoride (PVDF) or polyethersulfone (PES) filters. Different factors like formulation composition and protein concentration related to differences in viscosity, as well as different filtration rates were evaluated. The present study showed that filtration behavior was influenced by the presence or absence of a surfactant in the formulation, which defines the interaction between filter membrane and surface active formulation components. This can lead to a change in filter resistance (PES filter) independent on the buffer system used. Filtration behavior was additionally defined by rheological non-Newtonian flow behavior. The data showed that high shear rates resulting from small pore sizes and filtration pressure up to 1.0 bar led to shear-thinning behavior for highly concentrated protein formulations. Differences in non-Newtonian behavior were attributed to ionic strength related to differences in repulsive and attractive interactions. The present study showed that the interplay of formulation composition, filter material, and filtration rate can explain differences in filtration behavior/filtration flux observed for highly concentrated protein formulations thus guiding filter selection. PMID- 26149749 TI - Outbreak of colonization by carbapenemase-producing Klebsiella pneumoniae in a neonatal intensive care unit: Investigation, control measures and assessment. AB - We describe an outbreak of carbapenemase-producing Klebsiella pneumoniae in a neonatal intensive care unit and assess the effect of infection control measures. Our assessment indicates that active surveillance culture is very useful in identifying multidrug-resistant organisms and its prevention from transmission. Besides contact precaution, environment disinfection, good compliance of hand hygiene, and single-room isolation is very important for preventing transmission of carbapenemase-producing K pneumoniae isolates. PMID- 26149750 TI - Use of copper-silver ionization for the control of legionellae in alkaline environments at health care facilities. AB - BACKGROUND: There are multiple treatment options for the control of legionellae in premise hot water systems. Water chemistry plays a role in the efficacy of these treatments and should be considered when selecting a treatment. This study demonstrated the efficacy of copper-silver ionization (CSI) under alkaline water conditions in 2 health care facilities. METHODS: Monitoring for copper (Cu) and silver (Ag) ions was performed, and the corresponding percentage of positive Legionella cultures was monitored. Low Legionella colony forming units (CFU), with a mean <10 CFU/100 mL, and <=30% positive culture for each sampling period, along with no recurrent disease, were considered indicative of control. RESULTS: CSI treatment was shown to reduce both the number of CFU found and the percentage of samples found to be culture positive. After treatment was established, culture positivity was, for example, reduced from 70% (>10(3) CFU/100 mL) to consistently <30% (38 CFU/100 mL). CONCLUSION: Control of legionellae in premise water systems may be a complex process requiring long-term assessments for adequate control. This work found that CSI could be successful in controlling Legionella under alkaline water conditions, and the evidence suggests that Ag ions are responsible for the control of Legionella pneumophila 1, L pneumophila 6, and L anisa. PMID- 26149751 TI - Cognitive Predictors of Reasoning through Treatment Decisions in Patients with Newly Diagnosed Brain Metastases. AB - To examine the association between reasoning through medical treatment decisions and cognition in a sample of patients with brain metastasis. The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (i.e., intact or impaired). Results indicate that measures of episodic memory and processing speed were associated with reasoning. Using these two predictors, actuarial equations were constructed that can be used to help screen for impaired reasoning ability in patients' with brain metastasis. The equations presented in this study have clinical significance as they can be used to help identify patients at risk for possessing a diminished ability to reason through medical treatment decisions and, thus, are in need of a more comprehensive evaluation of their medical decision-making capacity. PMID- 26149752 TI - Prostate cancer, comorbidity, and the risk of venous thromboembolism: A cohort study of 44,035 Danish prostate cancer patients, 1995-2011. AB - BACKGROUND: Venous thromboembolism (VTE) is a serious complication of cancer. It is unknown whether comorbidity interacts clinically with prostate cancer (PC) to increase the VTE rate beyond that explained by PC and comorbidity alone, for example, by delaying diagnosis or precluding treatment. METHODS: A nationwide, registry-based cohort study of all 44,035 Danish patients diagnosed with PC from 1995 to 2011 and 213,810 men from the general population matched 5:1 on age, calendar time, and comorbidities. The authors calculated VTE rate ratios and the interaction contrast as a measure on the additive scale of the excess VTE rate explained by synergy between PC and comorbidity. RESULTS: In total, 849 patients in the PC cohort and 2360 men from the general population had VTE during 5 years of follow-up, and their risk of VTE was 2.2% and 1.3%, respectively. The 1-year VTE standardized rate among PC patients who had high comorbidity levels was 15 per 1000 person-years (PYs) (95% confidence interval, 6.8-24 per 1000 PYs), and 29% of that rate was explained by an interaction between PC and comorbidity. The VTE risk was increased among older patients, those with metastases, those with high Gleason scores, those in the D'Amico high-risk group, and those who underwent surgery. CONCLUSIONS: PC interacted clinically with high comorbidity levels and increased the VTE rate. Because of the large PC burden, reducing VTEs associated with comorbidities may have an impact on VTE risk and the potential to improve prognosis. Clinical interactions between high levels of comorbidity and PC on the risk of VTE were observed. Almost 30% of all episodes of VTE occurred among patients who had high levels of comorbidity. PMID- 26149753 TI - Solvent effects on the structures and vibrational features of zwitterionic dipeptides: L-diglycine and L-dialanine. AB - Calculations were done by applying the B3LYP/6-31++G(d) method on the zwitterionic L-diglycine and L-dialanine to study the solvent effects on their structures and vibrational features. Three models of solvation (implicit, explicit, and explicit in implicit) were used and the subsequent resulting values compared. Even though both dipeptides surrounded by 12 water molecules seem sufficient to stabilize their zwitterionic characters, notably to avoid the proton transfer between the backbone (N t H[Formula: see text], COO (-)) groups, the hybrid model of solvation (explicit in implicit noted 12W/Continuum) appears to be in better agreement with available IR and Raman experiments than explicit and implicit models. The harmonic vibrational modes derived from geometry optimization of L-diglycine and L-dialanine in 12W/Continuum, agree with the available IR and Raman experimental values within 1 % for L-diglycine and 2 % for L-dialanine, and they appear more accurate than those found using the explicit model (12W). Graphical Abstract DFT/6-31++G* Optimized structures of L-diglycine (top) and L-dialanine (bottom) surrounded by 12 water molecules all embedded in a continuum. PMID- 26149754 TI - Molecular model and ReaxFF molecular dynamics simulation of coal vitrinite pyrolysis. AB - Vitrinite in coal, the mainly generating methane maceral, plays an important role in hydrocarbon generation of coal. This study aims at obtaining products formation mechanism of vitrinite pyrolysis, and hence determining the chemical bond, molecular liquefaction activity, and reactions mechanism of methane and C2 4 during pyrolysis. The ReaxFF molecular dynamics (MD) simulation was carried out at temperature of 1500 K in order to investigate the mechanism of vitrinite pyrolysis. Initially, a minimum energy conformational structure model was constrained by a combination of elemental and carbon-13 nuclear magnetic resonance ((13)C NMR) literature data. The model analysis shows the chemical and physical parameters of vitrinite pyrolysis are broadly consistent with the experimental data. Based on the molecular model, ReaxFF MD simulations further provide information of unimolecule such as bond length, and chemical shift, and hence the total population and energy of main products. Molecules bond and pyrolysis fragments, based on active bond analyzed, revealed pyrolysis products of single vitrinite molecule with aliphatic C-C bond, especially ring and chain aliphatic as liquefaction activity. The molecular cell whose density is 0.9 g/cm(3) with lowest energy accords with the experimental density 1.33 g/cm(3). The content of main products after pyrolysis, classifying as CH4, H2O, and H2, was changed along with the increasing temperature. The gas molecule, fragments and generation pathways of CO2, H2, CH4, and C2H6 were also elucidated. These results show agreement with experimental observations, implying that MD simulation can provide reasonable explanation for the reaction processes involved in coal vitrinite pyrolysis. Thus the mechanism of coal hydrocarbon generation was revealed at the molecular level. PMID- 26149755 TI - The impact of ligands on the structure and flexibility of sulfotransferases: a molecular dynamics simulation study. AB - Sulfotransferases catalyze transfer of the sulfuryl-group (-SO3) from 3' phosphoadenosine 5'-phosphosulfate (PAPS) to a large number of substrates. They play an important role in phase II metabolic process. The impact of the cofactor (PAPS) on the structure and flexibility of the enzyme has been studied extensively, and the response of the active-cap region to cofactor binding was proposed as the molecular basis for substrate selectivity. In this study, individual and cooperative effects of the cofactor and substrate on the structure and flexibility of the enzyme were investigated. Molecular dynamics simulations were performed for four systems, including free enzyme, binary complexes (cofactor or substrate bound enzyme) and ternary complex (both cofactor and substrate bound enzyme). The influence of ligands (the cofactor and the substrate) on the structure and flexibility of the enzyme, especially that of the active-site cap region, was analyzed. Moreover, mutual structural impact of the ligands was examined as well. The results show that the impact of both the cofactor and the substrate was significant. Our study indicated that the substrate, such as lithocholic acid (LCA), participated in regulating the structure and flexibility of the enzyme actively rather than merely being selected passively. Additionally, the observed synergistic effects of the cofactor and the substrate demonstrated the importance of examining both ligands in understanding enzymes. PMID- 26149756 TI - Unfolded protein response in plants: one master, many questions. AB - To overcome endoplasmic reticulum (ER) stress, ER-localized stress sensors actuate distinct downstream organelle-nucleus signaling pathways to invoke a cytoprotective response, known as the unfolded protein response (UPR). Compared to yeast and metazoans, plant UPR studies are more recent but nevertheless fascinating. Here we discuss recent discoveries in plant UPR, highlight conserved and unique features of the plant UPR as well as critical yet-open questions whose answers will likely make significant contributions to the understanding plant ER stress management. PMID- 26149757 TI - Tyrosyl-DNA Phosphodiesterase I Inhibitors from the Australian Plant Macropteranthes leichhardtii. AB - Mass-directed isolation of the CH2Cl2/MeOH extract from the bark of an Australian plant, Macropteranthes leichhardtii, resulted in the purification of a new phenylpropanoid glucoside, macropteranthol (1), together with four known analogues (2-5). The structure of compound 1 was elucidated by NMR and MS data analyses and quantum chemical calculations. Compounds 3 and 5 showed inhibitory activity against tyrosyl-DNA phosphodiesterase I with IC50 values of ~1.0 MUM. PMID- 26149758 TI - Phylogeny and species delimitations in European Dicranum (Dicranaceae, Bryophyta) inferred from nuclear and plastid DNA. AB - DNA sequences have been widely used for taxonomy, inferring phylogenetic relationships and identifying species boundaries. Several specific methods to define species delimitations based on molecular phylogenies have appeared recently, with the generalized mixed Yule coalescent (GMYC) method being most popular. However, only few studies on land plants have been published so far and GMYC analyses of bryophytes are missing. Dicranum is a large genus of mosses whose (morpho-)species are partly ill-defined and frequently confused. To infer molecular species delimitations, we reconstructed phylogenetic trees based on five chloroplast markers and nuclear ribosomal ITS sequences from 27 out of 30 species occurring in Europe. We applied the species delimitation methods GMYC and Poisson tree processes (PTP) in order to compare their discriminatory power with species boundaries inferred from the molecular phylogenetic reconstructions and with the morphological species concept. Phylogenetic circumscriptions were congruent with the morphological concept for 19 species, while eight species were molecularly not well delimited, mostly forming closely related species pairs. The automated species delimitation methods achieved similar results but tended to overestimate the number of potential species and exposed several incongruences between the morphological concept and inference from molecular phylogenetic reconstructions. It is concluded that GMYC and PTP methods potentially provide a useful and objective way of delimiting bryophyte species, but studies on further bryophyte data sets are necessary to infer whether incongruences might ensue from evolutionary processes and to test the suitability of these approaches. PMID- 26149759 TI - Odanacatib for the treatment of osteoporosis. AB - INTRODUCTION: Osteoporosis and fragility fractures are important public health concerns. Cathepsin K inhibitors, including odanacatib , are a novel class of medications for osteoporosis whose mechanism of action is to directly inhibit bone resorption without killing osteoclasts, thereby permitting the complex coupling between bone resorption and formation to continue. AREAS COVERED: The physiological basis for the mechanism of action of cathepsin K inhibitors is covered in addition to a review of the preclinical, Phase I, Phase II and preliminary Phase III trial data of odanacatib. EXPERT OPINION: Evidence suggests that odanacatib has similar efficacy to bisphosphonates at increasing bone mineral density and decreasing risk of fragility fractures. Although odanacatib may preferentially inhibit bone resorption more than formation, the clinical significance of this difference in mechanism of action is not yet known. A careful analysis of the Phase III trial data is needed with specific attention to adverse events. PMID- 26149761 TI - Silver nanoparticles-induced cytotoxicity requires ERK activation in human bladder carcinoma cells. AB - Silver nanoparticles are toxic both in vitro and in vivo. We have investigated the possibility to exploit the cytotoxic potential of silver nanoparticles in T24 bladder carcinoma cells using both bare and PolyVinylPyrrolidone-coated silver nanoparticles. We show that the two types of silver nanoparticles promote morphological changes and cytoskeletal disorganization, are cytotoxic and induce cell death. These effects are due to the increased production of reactive oxygen species which are responsible, at least in part, for the sustained activation of ERK1/2. Indeed, both cytotoxicity and ERK1/2 activation are prevented by exposing the cells to the anti-oxidant N-acetylcysteine. Also blocking the ERK1/2 pathway with the MEK inhibitor PD98059 protects the cells from nanoparticles' cytotoxicity. Our findings suggest that ERK activation plays a role in silver nanoparticle-mediated cytotoxicity in T24 cells. PMID- 26149760 TI - Deregulation of NR2E3, an orphan nuclear receptor, by benzo(a)pyrene-induced oxidative stress is associated with histone modification status change of the estrogen receptor gene promoter. AB - We previously reported that NR2E3, an orphan nuclear receptor, plays an important role in maintaining the basal expression of estrogen receptor alpha (ER) and that the NR2E3 level is highly correlated with the relapse-free survival of breast cancer patients. Here, we investigated the role of NR2E3 in benzo(a)pyrene (BaP) mediated cell injury. BaP treatment reduced NR2E3 homo-dimer formation and expression and subsequently decreased ER expression. The chromatin immunoprecipitation assay results showed that the treatment of MCF-7 breast cancer cells and the mouse liver with BaP released NR2E3 from the ER promoter to transform the transcriptionally active histone modification status into a repressive state. NR2E3 depletion in MCF-7 cells also induced a similar inactive epigenetic status in the ER promoter region, indicating that NR2E3 is an essential epigenetic player that maintains basal ER expression. Interestingly, these negative effects of BaP on the expression levels of NR2E3 and ER were rescued by antioxidant treatment. Collectively, our study provides novel evidence to show that BaP-induced oxidative stress decreases ER expression, in part by regulating NR2E3 function, which modulates the epigenetic status of the ER promoter. NR2E3 is likely an essential epigenetic player that maintains basal ER expression to protect cells from BaP-induced oxidative injury. PMID- 26149762 TI - Flail arm syndrome with cytoplasmic vacuoles in remaining anterior horn motor neurons: A peculiar variant of amyotrophic lateral sclerosis. AB - Flail arm (FA) syndrome, a minor subtype of amyotrophic lateral sclerosis (ALS), is characterized by progressive weakness and upper girdle wasting, but the associated pathological changes remain unclear. A 59-year-old man was admitted to our hospital with a 3-year history of upper girdle weakness. Bulbar symptom and gait disturbance gradually developed, and he was clinically diagnosed with FA syndrome. After a 10-year disease course, he died of pulmonary adenocarcinoma. Neuropathological examination revealed severe motor neuronal loss in the brain stem and anterior horn of the cervical spinal cord with bilateral pyramidal tract degeneration. The histological findings were consistent with typical ALS, including Bunina bodies and Lewy body-like and skein-like inclusions. Cytoplasmic vacuoles were found in the remaining anterior horn motor neurons of the lumbar spinal cord. This is a unique autopsy case with a long-standing clinical course that suggests that FA syndrome is an atypical form of ALS. PMID- 26149763 TI - Health and educational success in adolescents: a longitudinal study. AB - BACKGROUND: Health in childhood and adolescence is a matter of contention. This article examines how infant and adolescent health act together with parental SES, health-related behaviour and academic factors to generate differences in the early life course with regard to later enrolment in higher education. METHODS: We used a questionnaire on health, The Oslo Health Study, which was linked to register data that provided detailed information on educational outcomes over time; and the Medical Birth Registry of Norway, which provided information on health at birth. RESULTS: It was found in the unadjusted results that infant health measures had a positive association with enrolment in higher education. After adjustment for adolescent health, there was still evidence that infant health are associated with enrolment in higher education. However, this association disappeared when parental socio-economic status (SES) was included in the model. Health in adolescents remains a significant and strong predictor of enrolment in higher education after adjusting for parental SES. However, the relationship between adolescent health and enrolment in higher education was reduced and became nonsignificant when adjustments were made to the health behaviour of the adolescents and their relationship with their families. Future educational expectations and good grades in grade 10 are strong predictors of enrolment in higher education. CONCLUSIONS: There are lower odds of enrolment in higher education for infants of low birthweight. However, this result seems to reflect the fact that parental SES correlate with both infant health and enrolment in higher education. Adolescent health are associated with enrolment in higher education, even after adjusting for parental SES. However, a considerable proportion of this association seems to be attributable to health-related behaviour and the relationship of the adolescent with his or her family. PMID- 26149765 TI - Fitness costs of intrinsic competition in two egg parasitoids of a true bug. AB - Intrinsic competition in insect parasitoids occurs when supernumerary larvae develop in the same host as consequence of multiple ovipositions by females of the same species (intra-specific competition) or by females of different species (inter-specific competition). Studies on intrinsic competition have mainly focused on understanding the factors that play a role in the outcome of competition, while fitness-related effects for the parasitoid surviving the competition have been poorly investigated, especially in egg parasitoids. Interestingly, even the winning parasitoid can experience fitness costs due to larval development in a host in which multiple factors have been injected by the ovipositing females or released by their larvae. In this paper we studied fitness related traits associated with intra- and inter-specific competition between Trissolcus basalis (Wollaston) and Ooencyrtus telenomicida (Vassiliev), the main egg parasitoids associated with the southern green stink bug Nezara viridula (L.) in Italy. We investigated the impact of intrinsic competition for the surviving parasitoid in terms of body size, developmental time, number and size of oocytes. Our results indicated that T. basalis adults did not experience fitness-related costs when surviving intra-specific competition; however, adults were smaller, took longer to develop and females produced fewer oocytes after surviving inter specific competition. A different outcome was found for O. telenomicida where the emerging females were smaller, produced fewer and smaller oocytes when suffering intra-specific competition whereas no fitness costs were found when adults survived inter-specific competition. These results support the hypothesis that the impact of intrinsic competition in egg parasitoids depends on the severity of the competitive interaction, as fitness costs were more pronounced when the surviving parasitoid interacted with the most detrimental competitor. PMID- 26149764 TI - Prevalence and risk factors of chronic kidney disease in urban adult Cameroonians according to three common estimators of the glomerular filtration rate: a cross sectional study. AB - BACKGROUND: Chronic kidney disease (CKD) is a major threat to the health of people of African ancestry. We assessed the prevalence and risk factors of CKD among adults in urban Cameroon. METHODS: This was a cross-sectional study of two months duration (March to April 2013) conducted at the Cite des Palmiers health district in the Littoral region of Cameroon. A multistage cluster sampling approach was applied. Estimated glomerular filtration rate (eGFR) was based on the Cockcroft-Gault (CG), the four-variable Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Logistic regression models were used to investigate the predictors of CKD. RESULTS: In the 500 participants with a mean age of 45.3 +/- 13.2 years included, we observed a high prevalence of overweight and obesity (60.4 %), hypertension (38.6 %) and diabetes (2.8 %). The mean eGFR was 93.7 +/- 24.9, 97.8 +/- 24.9 and 99.2 +/- 31.4 ml/min respectively with the MDRD, CG and CKD-EPI equations. The prevalence of albuminuria was 7.2 % while the prevalence of decreased GFR (eGFR < 60 ml/min) and CKD (any albuminuria and/or eGFR < 60 ml/min) was 4.4 and 11 % with MDRD, 5.4 and 14.2 % with CG, and 8.8 and 10 % with CKD-EPI. In age and sex adjusted logistic regression models, advanced age, known hypertension and diabetes mellitus, increasing body mass index and overweight/obesity were the predictors of albuminuria, decreased GFR and CKD according to various estimators. CONCLUSION: There is a high prevalence of CKD in urban adults Cameroonian, driven essentially by the commonest risk factors for CKD. PMID- 26149766 TI - Drosophila melanogaster larvae make nutritional choices that minimize developmental time. AB - Organisms from slime moulds to humans carefully regulate their macronutrient intake to optimize a wide range of life history characters including survival, stress resistance, and reproductive success. However, life history characters often differ in their response to nutrition, forcing organisms to make foraging decisions while balancing the trade-offs between these effects. To date, we have a limited understanding of how the nutritional environment shapes the relationship between life history characters and foraging decisions. To gain insight into the problem, we used a geometric framework for nutrition to assess how the protein and carbohydrate content of the larval diet affected key life history traits in the fruit fly, Drosophila melanogaster. In no-choice assays, survival from egg to pupae, female and male body size, and ovariole number - a proxy for female fecundity - were maximized at the highest protein to carbohydrate (P:C) ratio (1.5:1). In contrast, development time was minimized at intermediate P:C ratios, around 1:2. Next, we subjected larvae to two-choice tests to determine how they regulated their protein and carbohydrate intake in relation to these life history traits. Our results show that larvae targeted their consumption to P:C ratios that minimized development time. Finally, we examined whether adult females also chose to lay their eggs in the P:C ratios that minimized developmental time. Using a three-choice assay, we found that adult females preferentially laid their eggs in food P:C ratios that were suboptimal for all larval life history traits. Our results demonstrate that D. melanogaster larvae make foraging decisions that trade-off developmental time with body size, ovariole number, and survival. In addition, adult females make oviposition decisions that do not appear to benefit the larvae. We propose that these decisions may reflect the living nature of the larval nutritional environment in rotting fruit. These studies illustrate the interaction between the nutritional environment, life history traits, and foraging choices in D. melanogaster, and lend insight into the ecology of their foraging decisions. PMID- 26149767 TI - Mitochondrial DNA mutations in single human blood cells. AB - Determination mitochondrial DNA (mtDNA) sequences from extremely small amounts of DNA extracted from tissue of limited amounts and/or degraded samples is frequently employed in medical, forensic, and anthropologic studies. Polymerase chain reaction (PCR) amplification followed by DNA cloning is a routine method, especially to examine heteroplasmy of mtDNA mutations. In this review, we compare the mtDNA mutation patterns detected by three different sequencing strategies. Cloning and sequencing methods that are based on PCR amplification of DNA extracted from either single cells or pooled cells yield a high frequency of mutations, partly due to the artifacts introduced by PCR and/or the DNA cloning process. Direct sequencing of PCR product which has been amplified from DNA in individual cells is able to detect the low levels of mtDNA mutations present within a cell. We further summarize the findings in our recent studies that utilized this single cell method to assay mtDNA mutation patterns in different human blood cells. Our data show that many somatic mutations observed in the end stage differentiated cells are found in hematopoietic stem cells (HSCs) and progenitors within the CD34(+) cell compartment. Accumulation of mtDNA variations in the individual CD34+ cells is affected by both aging and family genetic background. Granulocytes harbor higher numbers of mutations compared with the other cells, such as CD34(+) cells and lymphocytes. Serial assessment of mtDNA mutations in a population of single CD34(+) cells obtained from the same donor over time suggests stability of some somatic mutations. CD34(+) cell clones from a donor marked by specific mtDNA somatic mutations can be found in the recipient after transplantation. The significance of these findings is discussed in terms of the lineage tracing of HSCs, aging effect on accumulation of mtDNA mutations and the usage of mtDNA sequence in forensic identification. PMID- 26149769 TI - Let them drink! PMID- 26149771 TI - Fiberoptic intubation with intraoral digital manipulation may be superior to C Mac videolaryngoscope in minimizing hypertensive response in cervical paraganlioma of the parapharyngeal area. PMID- 26149770 TI - Are nocturnal hypoxemia and hypercapnia associated with desaturation immediately after adenotonsillectomy? AB - BACKGROUND: Children who undergo adenotonsillectomy for sleep-disordered breathing frequently have postoperative oxygen desaturations. Nocturnal hypoxia has been shown to predict postoperative respiratory complications; however, other gas exchange abnormalities detected on polysomnography (PSG) have not been evaluated. AIM: We sought to determine whether hypercapnia seen on preoperative nocturnal PSG can predict postoperative hypoxemia. METHODS: We conducted a retrospective review of 319 children who underwent polysomnography before adenotonsillectomy. Saturation levels were recorded for at least 2 h postoperatively, and the primary outcome was desaturation (<90%). RESULTS: The median patient age was 5 years (range, 5 months-17 years). Patients who desaturated postoperatively had higher median peak endtidal CO2 (EtCO2 ) levels (55.5 vs 52 mmHg; P = 0.02), lower saturation nadirs (80.5% vs 88%; P = 0.048), and were younger (2 vs 6 years; P < 0.001) than those without desaturation. Age was significantly correlated with peak EtCO2 (r = -0.16), respiratory disturbance index (RDI; r = -0.23), and oxygen saturation nadir (r = 0.25; all P < 0.01). In unadjusted analysis, age <3 years compared to >=9 years (odds ratio [OR] = 10.09; 95% confidence interval [CI] = 2.13-96.26), peak EtCO2 > 55 mmHg (OR = 3.38; 95% CI = 1.21-9.47), and RDI >= 10 (OR = 2.89; 95% CI = 1.05-8.42) were associated with increased odds of desaturation. Multivariable logistic regression on age, race, sex, peak EtCO2 , RDI, opioid use, and saturation nadir showed that only age was significantly associated with postoperative desaturation. Patients 0-2 years old were 10.43 (95% CI = 1.89-110.9) times more likely to have desaturation than patients 9-17 years old. CONCLUSION: Patients <3 years of age are most likely to have postoperative hypoxemia after adenotonsillectomy. Gas exchange abnormalities did not correlate with postoperative desaturations, although age and peak EtCO2 did strongly correlate. PMID- 26149772 TI - Kikuchi-Fujimoto disease and life-threatening upper airway obstruction. PMID- 26149773 TI - lncRNAs and microRNAs with a role in cancer development. AB - Most diseases, including human cancer, are frequently associated with an altered transcription pattern. The alteration of the transcriptome is not restricted to the production of aberrant levels of protein-coding RNAs, but also refers to the dysregulation of the expression of the multiple noncoding members that comprise the human genome. Unexpectedly, recent RNA-seq data of the human transcriptome have revealed that less than 2% of the genome encodes protein-coding transcripts, even though the vast majority of the genome is actively transcribed into non coding RNAs (ncRNAs) under different conditions. In this review, we present an updated version of the mechanistic aspects of some long non-coding RNAs (lncRNAs) that play critical roles in human cancer. Most importantly, we focus on the interplay between lncRNAs and microRNAs, and the importance of such interactions during the tumorigenic process, providing new insight into the regulatory mechanisms underlying several ncRNA classes of importance in cancer, particularly transcribed ultraconserved regions (T-UCRs). This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26149775 TI - In pursuit of a science of agriculture: the role of statistics in field experiments. AB - Since the beginning of the twentieth century statistics has reshaped the experimental cultures of agricultural research taking part in the subtle dialectic between the epistemic and the material that is proper to experimental systems. This transformation has become especially relevant in field trials and the paper will examine the British agricultural institution, Rothamsted Experimental Station, where statistical methods nowadays popular in the planning and analysis of field experiments were developed in the 1920s. At Rothamsted statistics promoted randomisation over systematic arrangements, factorisation over one-question trials, and emphasised the importance of the experimental error in assessing field trials. These changes in methodology transformed also the material culture of agricultural science, and a new body, the Field Plots Committee, was created to manage the field research of the agricultural institution. Although successful, the vision of field experimentation proposed by the Rothamsted statisticians was not unproblematic. Experimental scientists closely linked to the farming community questioned it in favour of a field research that could be more easily understood by farmers. The clash between the two agendas reveals how the role attributed to statistics in field experimentation defined different pursuits of agricultural research, alternately conceived of as a scientists' science or as a farmers' science. PMID- 26149774 TI - Jmjd2C increases MyoD transcriptional activity through inhibiting G9a-dependent MyoD degradation. AB - Skeletal muscle cell differentiation requires a family of proteins called myogenic regulatory factors (MRFs) to which MyoD belongs. The activity of MyoD is under epigenetic regulation, however, the molecular mechanism by which histone KMTs and KDMs regulate MyoD transcriptional activity through methylation remains to be determined. Here we provide evidence for a unique regulatory mechanism of MyoD transcriptional activity through demethylation by Jmjd2C demethylase whose level increases during muscle differentiation. G9a decreases MyoD stability via methylation-dependent MyoD ubiquitination. Jmjd2C directly associates with MyoD in vitro and in vivo to demethylate and stabilize MyoD. The hypo-methylated MyoD due to Jmjd2C is significantly more stable than hyper-methylated MyoD by G9a. Cul4/Ddb1/Dcaf1 pathway is essential for the G9a-mediated MyoD degradation in myoblasts. By the stabilization of MyoD, Jmjd2C increases myogenic conversion of mouse embryonic fibroblasts and MyoD transcriptional activity with erasing repressive H3K9me3 level at the promoter of MyoD target genes. Collectively, Jmjd2C increases MyoD transcriptional activity to facilitate skeletal muscle differentiation by increasing MyoD stability through inhibiting G9a-dependent MyoD degradation. PMID- 26149776 TI - Foxp3 lacking exons 2 and 7 is unable to confer suppressive ability to regulatory T cells in vivo. AB - The forkhead/winged-helix transcription factor FOXP3 confers suppressive ability to CD4(+)FOXP3(+) regulatory T (Treg) cells. Human Treg cells express several different isoforms of FOXP3 that differ in function. However, the regulation and functional consequences of FOXP3 isoform expression remains poorly understood. In order to study the function of the FOXP3Delta2Delta7 isoform in vivo we generated mice that exclusively expressed a Foxp3 isoform lacking exon 2 and 7. These mice exhibited multi-organ inflammation, increased cytokine production, global T cell activation, activation of antigen-presenting cells and B cell developmental defects, all features that are shared with mice completely deficient in FOXP3. Our results demonstrate that the mouse counterpart of human FOXP3Delta2Delta7 is unable to confer suppressive ability to Treg cells. PMID- 26149777 TI - Is seroprevalence of hepatitis B and hepatitis C in Northeast India really high? PMID- 26149778 TI - Study of Human Biochemical Parameters During and After Ramadan. AB - Ramadan fasting is obligatory for Muslims each year. They abstain from drinking, eating and intimate relationship between dawn and dusk during this month. Dietary restriction during Ramadan has various biochemical and physiological effects. It is shown to decrease the body weight, glucose and lipid profile. This study aims to analyze the changes in body weight, glucose and lipid profile during Ramadan in physiotherapy students in Pakistan. The study was conducted during June-July 2013 (Hijri year 1434). There were 80 students (50 males and 30 females) recruited in the experiment. They all were healthy adults between the age group of 18-24 (mean age 20.5) years. All subjects underwent a general physical examination and interview, and non-healthy subjects were excluded. On statistical analysis, quantitative data were expressed in terms of mean +/- SD and a p value of <=0.05 was believed statically significant. Paired t test was used to compare the variables. There was a little reduction in body weight (62.7 +/- 8.8 vs. 62.3 +/- 9.0; p value = 0.009) but a significant decline in glucose level (72.6 +/- 12.5 vs. 57.9 +/- 10.7; p value = 0.000), low-density lipoprotein level (2.9 +/- 0.3 vs. 2.5 +/- 0.3; p value = 0.000), total cholesterol (4.6 +/- 0.4 vs. 4.2 +/- 0.5; p value = 0.000) and triglycerides (1.4 +/- 0.5 vs. 1.2 +/- 0.5; p value = 0.000) was observed. Moreover, there was some reduction in high-density lipoprotein cholesterol level (1.2 +/- 0.3 vs. 1.1 +/- 0.3; p value = 0.045). This study shows that Ramadan fasting, a religious obligation for purification of body and soul, resulted in reduced body weight and a positive effect on glucose level and lipid profile. PMID- 26149780 TI - Transdermal patches: past, present and future. PMID- 26149779 TI - In Silico Analysis of the Endonuclease III Protein Family Identifies Key Residues and Processes During Evolution. AB - DNA repair refers to a collection of processes by which a cell identifies and corrects damage to genomic DNA molecules. DNA repair processes significantly overcome DNA damage and restore the normal nucleotide sequence and DNA structure. This study focuses on the evolution of the endonuclease III gene/protein family, which plays a key role in the base excision repair pathway. We analyzed 463 homologs of the endonuclease III protein and compared them with the corresponding gene and 16S/18S rRNA sequences to understand the evolutionary processes of this protein family. The sequence analysis and comparison reveal consensus sequence motifs within the ENDO3c and iron-sulfur cluster loop domains that are functionally and structurally important. On the basis of phylogenetic analysis, we propose an evolutionary model of the endonuclease III protein family. Horizontal gene transfer was identified as the key event among bacteria, archaea, and eukaryotic organisms that occurred during the evolution of the endonuclease III gene family among bacteria, archaea, and eukaryotic organisms. This analysis may be exploited to achieve a better prediction of the endonuclease III family gene/protein in unannotated organisms or families of organisms that are completely sequenced as well as in those for which sequencing is ongoing. PMID- 26149781 TI - Exploring the potential of engineered coiled-coil protein microfibers in drug delivery. PMID- 26149783 TI - Transdermal iron replenishment therapy. AB - Iron deficiency anemia is one of the major nutritional deficiency disorders. Iron deficiency anemia occurs due to decreased absorption of iron from diet, chronic blood loss and other associated diseases. The importance of iron and deleterious effects of iron deficiency anemia are discussed briefly in this review followed by the transdermal approaches to deliver iron. Transdermal delivery of iron would be able to overcome the side effects associated with conventional oral and parenteral iron therapy and improves the patient compliance. During preliminary investigations, ferric pyrophosphate and iron dextran were selected as iron sources for transdermal delivery. Different biophysical techniques were explored to assess their efficiency in delivering iron across the skin, and in vivo studies were carried out using anemic rat model. Transdermal iron delivery is a promising approach that could make a huge positive impact on patients suffering with iron deficiency. PMID- 26149784 TI - The use of solid lipid nanoparticles for sustained drug release. AB - Novel solid lipid drug delivery systems such as solid lipid nanoparticles (SLN) have attracted wide and increasing attention in recent years. It has been sought as an interesting alternative drug delivery carrier system for bioactives for a variety of delivery routes. They show major advantages such as sustained release, improved bioavailability, improved drug incorporation and very wide application. This paper presents a discussion on the production protocols of SLN, lyophilization of SLN and delivery of SLN across the blood-brain barrier. Special attention was also paid to entrapment and release of drugs from SLN and strategies to enhance drug entrapment in SLN for sustained release. Analytical methods for the characterization of SLN were also discussed. Various routes of administration of SLN were presented as well as a consideration of the ethical issues and future prospects in the production and use of SLN for sustained release of bioactives. PMID- 26149785 TI - Trends in the development of oral anticoagulants. AB - Anticoagulation remains the therapy of choice for the prevention and treatment of venous and arterial thromboembolic disorders which can cause major organ damage or death. Heparins represent the antithrombotic drugs of choice in short and medium-term prophylaxis and therapy of thromboembolic diseases. Fondaparinux, a synthetic and structural analog of the antithrombin-binding pentasaccharide domain of heparin, has selective anti-Xa activity and longer half-life. However, anticoagulants are poorly absorbed by oral route because of their high molecular weight, hydrophilicity and negative charges. Long-term anticoagulation therapy is problematic because of side effects and frequent monitoring. Formulation approaches are particularly promising. PMID- 26149786 TI - Controlling drug delivery from coronary stents: are we aiming for the right targets? AB - In this review article, the currently employed or explored delivery concepts for local intravascular drug delivery with drug-eluting stents (DES) are discussed with a special emphasis on clinical evidence regarding the desired release profiles. Traditional concepts to control drug release from DES include diffusion through polymers, polymer degradation and erosion as well as dissolution of particulate drug. Published clinical studies do not always reveal fine mechanistic details. The long duration of release favored for DES and the short duration of release favored for drug-eluting balloons require further investigation in experimental studies and clinical trials. PMID- 26149787 TI - Understanding pharmaceutical polymorphic transformations II: crystallization variables and influence on dosage forms. AB - Excipients or formulation variables have often been exploited to improve stability, modify release, or improve physicochemical properties of dosage forms. In pharmaceutical field, it is generally expected that excipients work at macromolecular level where they might influence the crystal structure of a solid. These polymers/colloidal particles may modify the rate and direction of crystal growth. It has also been observed, that different polymorphic crystals exhibit different colors on exposure to same colorant, predominantly due to difference in surface pH of different crystal lattices. Apart from physicochemical affect, crystal habit also influences pharmacokinetic parameters of the dosage form. Crystals with smaller size or lower lattice energy have shown to exhibit higher bioavailability with faster rate of release. PMID- 26149788 TI - Modification of drug delivery to improve antibiotic targeting to the stomach. AB - The obstacles to the successful eradication of Helicobacter pylori infections include the presence of antibiotic-resistant bacteria and therapy requiring multiple drugs with complicated dosing schedules. Other obstacles include bacterial residence in an environment where high antibiotic concentrations are difficult to achieve. Biofilm production by the bacteria is an additional challenge to the effective treatment of this infection. Conventional oral formulations used in the treatment of this infection have a short gastric residence time, thus limiting the duration of exposure of drug to the bacteria. This review summarizes the current research in the development of gastroretentive formulations and the prospective future applications of this approach in the targeted delivery of drugs such as antibiotics to the stomach. PMID- 26149789 TI - Marking of verb tense in the English of preschool English-Mandarin bilingual children: evidence from language development profiles within subgroups on the Singapore English Action Picture Test. AB - BACKGROUND: The phonological and morphosyntactic structures of English and Mandarin contrast maximally and an increasing number of bilinguals speak these two languages. Speech and language therapists need to understand bilingual development for children speaking these languages in order reliably to assess and provide intervention for this population. AIMS: To examine the marking of verb tense in the English of two groups of bilingual pre-schoolers learning these languages in a multilingual setting where the main educational language is English. The main research question addressed was: are there differences in the rate and pattern of acquisition of verb-tense marking for English-language 1 children compared with Mandarin-language 1 children? METHODS & PROCEDURES: Spoken language samples in English from 481 English-Mandarin bilingual children were elicited using a 10-item action picture test and analysed for each child's use of verb tense markers: present progressive '-ing', regular past tense '-ed', third person singular '-s', and irregular past tense and irregular past-participle forms. For 4-6 year olds the use of inflectional markers by the different language dominance groups was compared statistically using non-parametric tests. OUTCOMES & RESULTS: This study provides further evidence that bilingual language development is not the same as monolingual language development. The results show that there are very different rates and patterns of verb-tense marking in English for English-language 1 and Mandarin-language 1 children. Furthermore, they show that bilingual language development in English in Singapore is not the same as monolingual language development in English, and that there are differences in development depending on language dominance. CONCLUSIONS: Valid and reliable assessment of bilingual children's language skills needs to consider the characteristics of all languages spoken, obtaining accurate information on language use over time and accurately establishing language dominance is essential in order to make a differential diagnosis between language difference and impairment. PMID- 26149790 TI - Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1beta secretion in response to anti-MPO antibodies. AB - ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1beta, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1beta in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells. PMID- 26149791 TI - Genomic deletions and mutations resulting in the loss of eight genes reduce the in vivo replication capacity of Meleagrid herpesvirus 1. AB - Meleagrid herpesvirus 1 (MeHV-1 or turkey herpesvirus) has been widely used as a vaccine in commercial poultry. Initially, these vaccine applications were for the prevention of Marek's disease resulting from Gallid herpesvirus 2 infections, while more recently MeHV-1 has been used as recombinant vector for other poultry infections. The construction of herpesvirus infectious clones that permit propagation and manipulation of the viral genome in bacterial hosts has advanced the studies of herpesviral genetics. The current study reports the construction of five MeHV-1 infectious clones. The in vitro properties of viruses recovered from these clones were indistinguishable from the parental MeHV-1. In contrast, the rescued MeHV-1 viruses were significantly attenuated when used in vivo. Complete sequencing of the infectious clones identified the absence of two regions of the MeHV-1 genome compared to the MeHV-1 reference sequence. These analyses determined the rescued viruses have seven genes, UL43, UL44, UL45, UL56, HVT071, sorf3 and US2 either partially or completely deleted. In addition, single nucleotide polymorphisms were identified in all clones compared with the MeHV-1 reference sequence. As a consequence of one of the polymorphisms identified in the UL13 gene, four of the rescued viruses were predicted to encode a serine/threonine protein kinase lacking two of three domains required for activity. Thus four of the recovered viruses have a total of eight missing or defective genes. The implications of these findings in the context of herpesvirus biology and infectious clone construction are discussed. PMID- 26149792 TI - A theoretical study of imine hydrocyanation catalyzed by halogen-bonding. AB - A detailed theoretical study of the mechanism and energetics of an organocatalysis based on C=N activation by halogen-bonding is presented for the hydrocyanation of N-benzylidenemethylamine. The calculations at the level of scalar-relativistic gradient-corrected density functional theory give an insight in this catalytic concept and provide information on the characteristics of four different monodentate catalyst candidates acting as halogen-bond donors during the reaction. PMID- 26149793 TI - IL-1beta associations with posttraumatic epilepsy development: A genetics and biomarker cohort study. AB - OBJECTIVE: Posttraumatic epilepsy (PTE) is a significant complication following traumatic brain injury (TBI), yet the role of genetic variation in modulating PTE onset is unclear. We hypothesized that TBI-induced inflammation likely contributes to seizure development. We assessed whether genetic variation in the interleukin-1beta (IL-1beta) gene, Il-1beta levels in cerebral spinal fluid (CSF) and serum, and CSF/serum IL-1beta ratios would predict PTE development post-TBI. METHODS: We investigated PTE development in 256 Caucasian adults with moderate-to severe TBI. IL-1beta tagging and functional single nucleotide polymorphisms (SNPs) were genotyped. Genetic variance and PTE development were assessed. Serum and CSF IL-1beta levels were collected from a subset of subjects (n = 59) during the first week postinjury and evaluated for their associations with IL-1beta gene variants, and also PTE. Temporally matched CSF/serum IL-1beta ratios were also generated to reflect the relative contribution of serum IL-1beta to CSF IL-1beta. RESULTS: Multivariate analysis showed that higher CSF/serum IL-1beta ratios were associated with increased risk for PTE over time (p = 0.008). Multivariate analysis for rs1143634 revealed an association between the CT genotype and increased PTE risk over time (p = 0.005). The CT genotype group also had lower serum IL-1beta levels (p = 0.014) and higher IL-1beta CSF/serum ratios (p = 0.093). SIGNIFICANCE: This is the first report implicating IL-1beta gene variability in PTE risk and linking (1) IL-1beta gene variation with serum IL 1beta levels observed after TBI and (2) IL-1beta ratios with PTE risk. Given these findings, we propose that genetic and IL-1beta ratio associations with PTE may be attributable to biologic variability with blood-brain barrier integrity during TBI recovery. These results provide a rationale for further studies (1) validating the impact of genetic variability on IL-1beta production after TBI, (2) assessing genetically mediated signaling mechanisms that contribute to IL 1beta CSF/serum associations with PTE, and (3) evaluating targeted IL-1beta therapies that reduce PTE. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. PMID- 26149794 TI - Valproate still has a place in women with epilepsy. PMID- 26149795 TI - Commentary on Long-term seizure outcome in 211 patients with focal cortical dysplasia. PMID- 26149796 TI - In response: Long-term seizure outcome in 211 patients with focal cortical dysplasia. PMID- 26149797 TI - Why should we change the term psychogenic nonepileptic seizures? PMID- 26149798 TI - In Response: Terminology of psychogenic nonepileptic seizures-a Babel of different names? PMID- 26149799 TI - Ca(v)2.3 R-type Ca(2+) channels in anticonvulsive treatment. PMID- 26149800 TI - Sertraline-carbamazepine neurotoxic interaction: Fiction or fact? PMID- 26149801 TI - In response: Cav2.3 (R-type) calcium channels are critical for mediating anticonvulsive and neuroprotective properties of lamotrigine in vivo. PMID- 26149802 TI - Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo-HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: a retrospective, multicenter Polish Adult Leukemia Group study. AB - The importance of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999-2008. The Mantel-Byar approach was used to assess allo-HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41-60. The CIR demonstrated that allo-HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo-HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41-60. The allo-HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis. PMID- 26149803 TI - Trends and Characteristics of Emergency Department Patients Prescribed Novel Oral Anticoagulants. AB - BACKGROUND: Since 2010, several novel oral anticoagulants (NOACs) have been approved by the United States Food and Drug Administration for the use in the prevention of cerebrovascular accidents (CVAs) in nonvalvular atrial fibrillation. OBJECTIVE: Our aim was to describe the trends and characteristics of NOAC-related emergency department (ED) visits. METHODS: Retrospective review of data from an ED tracking system of all visits that had a medication reconciliation with an NOAC or warfarin to a tertiary care ED between October 2010 and August 2014. Basic demographics, admission rate, admission diagnoses, and trends were analyzed. RESULTS: The rate of warfarin visits was stable at 50 60 patients per month (PPM) per 1000 ED visits, however, the rate of dabigatran visits rose to 3-5 PPM/1000 until 2012 and has stayed stable, while rivaroxaban and apixaban have been gradually increasing to 2-4 and 1-2 PPM/1000, respectively. The admission rate for warfarin was 63.7% and for NOACs was 58.1%, compared to baseline admission rate of 35.5%. The hemorrhagic diagnosis rate was similar for warfarin and the NOACs (8.8% and 8.0%, respectively). There were three significantly different admission diagnoses: there were more admission for atrial fibrillation (5.4% vs. 1.9%) and CVA/transient ischemic attack (5.3% vs. 3.0%) in the NOAC group, while there were more admissions for intracranial hemorrhage (2.7% vs. 0.8%) in the warfarin group. CONCLUSIONS: There has been a steady increase of ED patients who are taking an NOAC. There is a nearly double admission rate for an anticoagulated patient regardless of reason for ED visit. There appears to be no difference between rates of bleeding between warfarin and NOACs, although patients taking NOACs are admitted less often for intracranial hemorrhage. PMID- 26149804 TI - A Curious Case of Cold Ludwig's Angina. PMID- 26149805 TI - Memoriam to Richard Edlich, MD. PMID- 26149806 TI - Malignant Pericardial Effusion in Ovarian Malignancy: A Treatable Oncologic Emergency. AB - BACKGROUND: Pericardial tamponade is a life-threatening condition that can occur, albeit rarely, in patients with ovarian cancer. Whether or not prolonged survival is possible after such an event is debatable. Our aim was to describe our experience with seven ovarian cancer patients who experienced malignant cardiac tamponade at tumor diagnosis or at recurrence. CASE REPORT: Six patients were treated with pericardiocentesis and one with pericardial fenestration. Survival after tamponade ranged from 3 to 72 weeks. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We suggest that when pericardial effusion occurs in patients with recurrent ovarian cancer, timely diagnosis and proper management might allow palliation and prolongation of life. PMID- 26149807 TI - From the laboratory to the clinic: How translational studies in animals have lead to clinical advances in boron neutron capture therapy. AB - In this report five examples have been selected to illustrate how studies in experimental animals have lead directly to clinical implementation. These include (1) the use of BSH as a boron delivery agent for BNCT of patients with brain tumors, and more specifically gliomas; (2) the use of BPA as a delivery agent for BNCT for patients with melanomas and (3) its subsequent use for BNCT of patients with gliomas; (4) optimization of the delivery of BPA in patients with gliomas; and finally (5) the combination of BSH and BPA with BNCT alone or together with X irradiation to treat patients with gliomas. PMID- 26149809 TI - Hyperkeratotic lesions and pruritus in an immunosuppressed patient. PMID- 26149808 TI - Deletion of Phenylalanine 508 in the First Nucleotide-binding Domain of the Cystic Fibrosis Transmembrane Conductance Regulator Increases Conformational Exchange and Inhibits Dimerization. AB - Deletion of Phe-508 (F508del) in the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) results in destabilization of the domain, intramolecular interactions involving the domain, and the entire channel. The destabilization caused by F508del manifests itself in defective channel processing and channel gating defects. Here, we present NMR studies of the effect of F508del and the I539T stabilizing mutation on NBD1 dynamics, with a view to understanding these changes in stability. Qualitatively, F508del NMR spectra exhibit significantly more peak broadening than WT spectra due to the enhanced intermediate time scale (millisecond to microsecond) motions in the mutant. Unexpectedly, studies of fast (nanosecond to picosecond) motions revealed that F508del NBD1 tumbles more rapidly in solution than WT NBD1. Whereas F508del tumbles at a rate nearly consistent with the monomeric state, the WT protein tumbles significantly more slowly. Paramagnetic relaxation enhancement experiments confirm that NBD1 homodimerizes in solution in the expected head-to tail orientation. NMR spectra of WT NBD1 reveal significant concentration dependent chemical shift perturbations consistent with NBD1 dimerization. Chemical shift analysis suggests that the more rapid tumbling of F508del is the result of an impaired ability to dimerize. Based on previously published crystal structures and NMR spectra of various NBD1 mutants, we propose that deletion of Phe-508 affects Q-loop conformational sampling in a manner that inhibits dimerization. These results provide a potential mechanism for inhibition of channel opening by F508del and support the dimer interface as a target for cystic fibrosis therapeutics. PMID- 26149810 TI - Pulmonary cysts associated with primary Sjogren's syndrome. PMID- 26149811 TI - Risk factors for development of isthmocele following cesarean section. AB - AIM: The aim of this paper was to analyze the risk factors contributing to the development of isthmocele following cesarean section (CS). METHODS: We retrospectively analyzed a cohort of patients presenting to our outpatient clinic for hysteroscopy. Only premenopausal patients with a history of CS were included. The risk factors investigated were: occurrence of previous vaginal delivery antecedent to CS, patient's age at CS, weeks of gestation at CS, phase of labor, type of suture (single/double layer) employed, and uterine flexion (anteversion/retroversion). RESULTS: The association between the identified risk factors and the occurrence of isthmocele was found statistical significant concerning indication for hysteroscopy (c2), stage of labor (c2), age at CS (Mann Withney U test), according to the univariate analysis. This association was then confirmed in the multivariate logistic regression model pooling all the variables together. CONCLUSION: The significance of stage of labor to the development of isthmocele confirms previous observations and may be part of the information needed to the clinical decision of the CS time setting decision for the clinicians. Nevertheless, further prospective studies employing larger cohorts are warranted to further clarify the aforementioned risk factors before suggesting any modifications of clinical practice. PMID- 26149812 TI - Study of serum paraoxonase and phospholipase activities in pregnant women in relation to birth weight. AB - AIM: Low birth weight is an important issue due to its dreadful consequences in future. Well prevailing over the world, this is important in view of developing countries. Low birth weight is associated with high neonatal and infant mortality, lower trajectory of growth during childhood and adolescence, increases risk of non-communicable diseases during adult life. Oxidative stress is a major player among the various etiologies. Paraoxonase1 is an important antioxidant defense. Phospholipase is required to release free fatty acids from phosphoglycerides utilized for fetal growth. We conducted the study to look for the predictive value of serum paraoxonase and phospholipase. METHODS: With binding to Helsinki declaration and approval from Institutional Ethical Committee, we have selected 100 pregnant ladies. Serum PON1 arylesterase (ARE), lactonase (LACT) and serum phospholipase (PL) activities are measured. We used SPSS 20.0 for linear and logistic regression models to assess the predictability of the ARE, LACT and PL for predicting the IUGR. RESULTS: R value increases in the order of maternal age, maternal weight, phospholipase, arylesterase, lactonase. Logistic regression analysis with different models and with birth weight as dependent factor, maternal age is flagged out as not significant. PL, LACT, ARE emerge out to be good predictors of IUGR. CONCLUSION: From this study we have concluded that PON1 LACT, ARE and serum PL, could be the newer markers IUGR in maternal serum. IUGR can be predicted beforehand by using PON1 LACT, PON1 ARE and serum phospholipase. This surely will help in timely diagnosis and treatment accordingly of possible adverse pregnancy outcome. PMID- 26149813 TI - Diagnosis, antenatal surveillance and management of prolonged pregnancy: current perspectives. AB - Prolonged pregnancy is defined as a pregnancy that extends beyond 42 weeks of gestation (294 days) from the first day of the last normal menstrual period. An accurate estimation of the 'natural' incidence of prolonged pregnancy would require meticulous early pregnancy dating. The use of ultrasound to establish gestational age reduces the number of pregnancies that are classified as prolonged. Prolonged pregnancy is associated with an increased perinatal mortality and morbidity in pregnancies which appear to be otherwise low risk. Postterm births are easily preventable by intervening to deliver with the use of induction of labor. Thus, this potentially problematic condition deserves further attention and careful consideration. The focus of this article is to review and challenge some current concepts surrounding the diagnosis and management of prolonged pregnancy. We outline how to identify those women with prolonged pregnancy and which is the appropriate moment to start monitoring the fetal wellbeing. Finally we address the question of benefits and hazards of induction of labor strategies. PMID- 26149815 TI - Preface. PMID- 26149814 TI - Pleural metastasis of ovarian cancer. A price to pay for debulking the upper abdomen. PMID- 26149816 TI - Reflex Testing Rules for Cell Count and Differentiation of Nucleated Elements in Pleural and Ascitic Fluids on Sysmex XE-5000. AB - Flow cytometry is widely used in many laboratories for automated nucleated cell counts and their differentiation in body fluids. The implementation of new reflex testing rules on these automated instruments could open new frontiers in laboratory workflow, improving characterization of body fluids and clinical diagnosis and decreasing costs. Ascitic (150) and pleural (33) fluids were collected and assessed by XE-5000 and optical microscopy. Cell counts performed with the methods showed a Pearson's correlation of 0.98 (p < 0.0001), Passing Bablok regression y = 0.99x + 2.44, and bias of 32.3. In ascitic fluids, the best diagnostic performance was found for polymorphonuclear and neutrophil counts on XE-5000, which exhibited areas under the curve (AUCs) 0.98 (p < 0.0001) and 0.99 (p < 0.0001), respectively. In pleural fluids the best diagnostic performance was found for polymorphonuclear percent parameter, which displayed 0.97 (p < 0.0001). Specific reflex test rules based on these parameters were characterized by 92% diagnostic concordance, 1.00 sensitivity, and 0.84 specificity with optical microscopy. The application of a set of reflex testing rules may improve the diagnostic performance of XE-5000, increasing its reliability for routine automated cell count in body fluids. We acknowledge that further studies should be planned to validate our findings according to clinical data. PMID- 26149817 TI - Identifying cancer patients who alter care or lifestyle due to treatment-related financial distress. AB - BACKGROUND: Cancer patients may experience financial distress as a side effect of their care. Little is known about which patients are at greatest risk for altering their care or lifestyle due to treatment-related financial distress. METHODS: We conducted a cross-sectional survey study to determine which patients are at greatest risk for altering their care or lifestyle due to treatment related financial distress. Eligible patients were adults receiving cancer treatment enrolled between June 2010 and May 2011. We grouped coping strategies as lifestyle altering or care altering. We assessed coping strategies and relationships between covariates using descriptive statistics and analysis of variance. RESULTS: Among 174 participants, 89% used at least one lifestyle altering coping strategy, while 39% used a care-altering strategy. Care-altering coping strategies adopted by patients included the following: not filling a prescription (28%) and taking less medication than prescribed (23%). Lifestyle altering strategies included the following: spending less on leisure activities (77%), spending less on basics like food and clothing (57%), borrowing money (54%), and spending savings (50%). Younger patients were more likely than older patients to use coping strategies (p < 0.001). Lower-income patients adopted care altering strategies more than higher-income patients (p = 0.03). Participants with more education and shorter duration of chemotherapy used lifestyle-altering strategies more than their counterparts (both p < 0.05). CONCLUSIONS: As a means of coping with treatment-related financial distress, patients were more likely to use lifestyle-altering approaches, but more than one-third adopted potentially harmful care-altering strategies. Younger age, lower income, higher education, and shorter duration of chemotherapy were characteristics associated with greater use of coping strategies. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26149818 TI - Synthesis of magnetic metal-organic framework (MOF) for efficient removal of organic dyes from water. AB - A novel, simple and efficient strategy for fabricating a magnetic metal-organic framework (MOF) as sorbent to remove organic compounds from simulated water samples is presented and tested for removal of methylene blue (MB) as an example. The novel adsorbents combine advantages of MOFs and magnetic nanoparticles and possess large capacity, low cost, rapid removal and easy separation of the solid phase, which makes it an excellent sorbent for treatment of wastewaters. The resulting magnetic MOFs composites (also known as MFCs) have large surface areas (79.52 m(2) g(-1)), excellent magnetic response (14.89 emu g(-1)), and large mesopore volume (0.09 cm(3) g(-1)), as well as good chemical inertness and mechanical stability. Adsorption was not drastically affected by pH, suggesting pi-pi stacking interaction and/or hydrophobic interactions between MB and MFCs. Kinetic parameters followed pseudo-second-order kinetics and adsorption was described by the Freundlich isotherm. Adsorption capacity was 84 mg MB g(-1) at an initial MB concentration of 30 mg L(-1), which increased to 245 mg g(-1) when the initial MB concentration was 300 mg L(-1). This capacity was much greater than most other adsorbents reported in the literature. In addition, MFC adsorbents possess excellent reusability, being effective after at least five consecutive cycles. PMID- 26149819 TI - A novel approach to biocontrol: Release of live insect hosts pre-infected with entomopathogenic nematodes. AB - As a new application approach, we tested the efficacy of releasing live insect hosts that were pre-infected with entomopathogenic nematodes against insect pests living in cryptic habitats. We hypothesized that the pre-infected hosts could carry the next generation of emerging nematode infective juveniles to hard-to reach target sites, and thereby facilitate enhanced control in cryptic habitats. Thus, the infected hosts act as "living insect bombs" against the target pest. We tested this approach using two model insect pests: a chestnut tree pest, the goat moth Cossus cossus (Lepidiptera: Cossidae), and a lawn caterpillar, Spodoptera cilium (Lepidoptera: Noctuidae). One pest is considered hard-to-reach via aqueous spray (C. cossus) and the other is more openly exposed in the environment (S. cilium). C. cossus and S. cilium studies were conducted in chestnut logs and Bermudagrass arenas, respectively. The living bomb approach was compared with standard nematode application in aqueous spray and controls (without nematode application); Steinernema carpocapsae (Rize isolate) was used in all experiments. The percentage larval mortality of C. cossus was 86% in the living insect bomb treatment, whereas, all other treatments and controls exhibited less than 4% mortality. The new approach (living bomb) was equally successful as standard aqueous application for the control of S. cilium larvae. Both methods exhibited more than 90% mortality in the turfgrass arena. Our new approach showed an immense potential to control insect pests living in hard-to-reach cryptic habitats. PMID- 26149820 TI - Detection of Marteilia refringens infecting the European flat oyster Ostrea edulis and the dwarf oyster Ostrea stentina in southern Portugal and Spain. AB - In the present study, Marteilia sp. was detected by histological examination and in situ hybridisation in Ostrea edulis and Ostrea stentina collected in southern Iberian Peninsula. Marteilia refringens DNA was detected by PCR in O. edulis (collected in southern Portugal) and O. stentina (collected in southern Spain and Portugal). Sequencing analysis revealed the presence of M. refringens type O in O. edulis, and type O and M in O. stentina. This is the first confirmed detection of M. refringens in Portugal and the first report on the occurrence of M. refringens infecting O. stentina in Europe. PMID- 26149821 TI - Benomyl treatment decreases fecundity of ant queens. AB - Methyl benzimidazole carbamate fungicides, including benomyl, are widely used in agriculture, and to eliminate entomopathogenic infections. We treated queens of Myrmica rubra (Hymenoptera:Formicidae) infected or not by Rickia wasmannii (Laboulbeniales:Laboulbeniaceae) with benomyl, 1mg/ml p.o. for six weeks. Benomyl did not treat the infection, and the treatment alone caused strong decrease in the fecundity of control healthy queens from 18.0+/-8.4 to 3.7+/-5.2eggs per healthy queen. This is the first evidence on severe adverse effects of methyl benzimidazole carbamate fungicide on the fecundity of insects, which might be responsible for altered species composition of ant assemblages in the cultural landscape. PMID- 26149822 TI - Early transcriptional response to the parasitic dinoflagellate Hematodinium in hepatopancreas of Portunus trituberculatus. AB - The swimming crab Portunus trituberculatus supports a large proportion of crab aquaculture in China. In the last decade, the sustainable culture of this crab was threatened by the parasitic dinoflagellate Hematodinuim, resulting in massive mortality (up to 95%) in severely impacted culture ponds. Previous studies of Hematodinium were mainly focused on histology, molecular characterization, epizootiology, etc., with limited studies conducted to explore this specific host parasite interaction. Thus, to give a primary insight into the anti-parasitic immune response at the critical stage of infection, the expression levels of 8 immune-related genes together with enzyme activities of phenoloxidase (PO), alkaline phosphatase (AKP), and acid phosphatase (ACP), were evaluated in hepatopancreas during 3-192h (h) post inoculation. Hematoxylin-eosin (H&E) staining showed noticeable pathological changes in hepatopancreas. The enzyme activities of PO, AKP, and ACP were significantly induced after inoculation. The changes of the prophenoloxidase (proPO) transcripts and the constantly enhanced PO activity reflected the critical function of the proPO system in resisting against the parasites. The decreased expression levels of LGBP and PPAF implied an immunosuppressive mechanism of the parasites against the host proPO system. And the significant variations in transcriptional levels of two important proteinase inhibitors (serpin, alpha2m) and three P. trituberculatus clip-domain serine proteinases (PTcSPs) suggested that the parasites could affect proteinase cascade reactions associated with immune response by destroying the balance between serine proteinases and the inhibitors. Moreover, the results indicated that the hepatopancreas of P. trituberculatus was significantly affected by invasion of the parasite, and hepatopancreas played important roles in the crustacean innate immunity against the parasitic infection. PMID- 26149823 TI - Short-term heat shock affects the course of immune response in Galleria mellonella naturally infected with the entomopathogenic fungus Beauveria bassiana. AB - We aimed to investigate how exposition of infected insects to short-term heat shock affects the biochemical and molecular aspects of their immune response. Galleria mellonella larvae were exposed to 43 degrees C for 15min, at the seventy second hour after natural infection with entomopathogenic fungus Beauveria bassiana. As a result, both qualitative and quantitative changes in hemolymph protein profiles, and among them infection-induced changes in the amount of apolipophorin III (apoLp-III), were observed. Heat shock differently affects the expression of the tested immune-related genes. It transiently inhibits expression of antifungal peptides gallerimycin and galiomicin in both the fat body and hemocytes of infected larvae. The same, although to a lesser extent, concerned apoLp-III gene expression and was observed directly after heat shock. Nevertheless, in larvae that had recovered from heat shock, apoLp-III expression was higher in comparison to unshocked larvae in the fat body but not in hemocytes, which was consistent with the higher amount of this protein detected in the hemolymph of the infected, shocked larvae. Furthermore, lysozyme-type activity was higher directly after heat shock, while antifungal activity was significantly higher also in larvae that had recovered from heat shock, in comparison to the respective values in their non-shocked, infected counterparts. These results show how changes in the external temperature modulate the immune response of G. mellonella suffering from infection with its natural pathogen B. bassiana. PMID- 26149824 TI - Parasitized honey bees are less likely to forage and carry less pollen. AB - Research into loss of pollination capacity has focused primarily on documenting pollinator declines and their causes with comparatively little attention paid to how stressors may affect pollinating behavior of surviving pollinators. The European honey bee, Apis mellifera is one of the world's most important generalist pollinators, and Nosema apis is a widespread microsporidian gut parasite of adult A. mellifera. We individually fed 960 newly eclosed A. mellifera workers either a sucrose solution or 400 N. apis spores in a sucrose solution and tagged them with a unique radio frequency identification (RFID) tag to monitor their foraging behavior. We found spore-fed bees were less likely to forage than those fed sugar only. Those that did forage started foraging when they were older and stopped foraging when they were younger than bees fed sugar only. However, inoculated and non-inoculated bees did not significantly differ in the number of foraging trips taken per day, the total hours foraged over their lifetime, or homing ability. Inoculated returning foragers were 4.3 times less likely to be carrying available pollen than non-inoculated returning foragers and the number of pollen grains carried was negatively correlated with the number of N. apis spores. In an arena of artificial flowers, inoculated bees had a tendency (p=0.061) to choose sugar flowers over pollen flowers, compared to non-inoculated bees which visited pollen and sugar flowers equally. These results demonstrate that even a relatively low dose of a widespread disease of A. mellifera may adversely affect bees' ability to pollinate. PMID- 26149825 TI - Modified obstetric early warning systems. PMID- 26149826 TI - Reply: To PMID 25797235. PMID- 26149827 TI - The risk of stillbirth and infant death by each additional week of expectant management in twin pregnancies. PMID- 26149829 TI - Cost and effects of risk factor guided screening strategies for retinopathy of prematurity for different treatment strategies. AB - PURPOSE: To investigate the cost and effects of risk factor guided screening strategies for retinopathy of prematurity. METHODS: Clinical data from the Netherlands Retinopathy of Prematurity study (NEDROP study) that included all infants screened for ROP and born in 2009 were used to assess the cost and effects of several screening strategies for ROP using different criteria: (1) gestational age (GA), (2) birthweight (BW), (3) combined GA-BW and (4) combined GA-BW and presence of risk factors. Two treatment strategies were evaluated: the infants actually treated in the NEDROP study (n = 17) and all infants detected with severe ROP (n = 29). RESULTS: The most efficient screening strategy to include all infants treated for both treatment strategies is to screen all infants with a GA of 30 weeks or less and a BW of 1250 g or lower together with infants with a GA of 30-32 weeks and a BW of 1250-1500 g with at least one risk factor. The marginal cost ranged from ?43 848 to ? 226 914 per additional infant with improved vision. CONCLUSION: The current Dutch guideline may be improved: the same effectiveness can be obtained for lower costs. Releasing the precondition that no infants with severe ROP might be missed will lead to lower costs, but this will also lead to a lower number of infants with improved visual acuity. The costs of detecting all infants with severe ROP seem acceptable for society when the QALY gain and savings from a societal perspective resulting from improved vision are taken into account. PMID- 26149828 TI - Cervical phosphorylated insulin-like growth factor binding protein-1 test for the prediction of preterm birth: a systematic review and metaanalysis. AB - OBJECTIVE: To assess the accuracy of the cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) test to predict preterm birth in women with and without symptoms of preterm labor through the use of formal methods for systematic reviews and metaanalytic techniques. DATA SOURCES: PubMed, Embase, Cinahl, Lilacs, and Medion (all from inception to June 30, 2015), reference lists, conference proceedings, and Google scholar. STUDY ELIGIBILITY CRITERIA: Cohort or cross-sectional studies that reported on the predictive accuracy of the cervical phIGFBP-1 test for preterm birth. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently selected studies, assessed the risk of bias, and extracted the data. Summary receiver-operating characteristic curves, pooled sensitivities and specificities, and summary likelihood ratios were generated. RESULTS: Forty-three studies met the inclusion criteria, of which 15 provided data on asymptomatic women (n = 6583) and 34 on women with an episode of preterm labor (n = 3620). Among asymptomatic women, the predictive accuracy of the cervical phIGFBP-1 test for preterm birth at <37, <34, and <32 weeks of gestation was minimal, with pooled sensitivities and specificities and summary positive and negative likelihood ratios ranging from 14% to 47%, 76% to 93%, 1.5 to 4.4, and 0.6 to 1.0, respectively. Among women with an episode of preterm labor, the test had a low predictive performance for delivery within 7 and 14 days of testing, and preterm birth at <34 and <37 weeks of gestation with pooled sensitivities and specificities and summary positive and negative likelihood ratios that varied between 60% and 68%, 77% and 81%, 2.7 and 3.5, and 0.4 and 0.5, respectively. A negative test result in women with an episode of preterm labor had a low to moderate accuracy to identify women who are not at risk for delivering within the next 48 hours (summary negative likelihood ratio of 0.28 in all women and 0.23 in women with singleton gestations). CONCLUSION: Cervical phIGFBP-1 has the potential utility to identify patients with an episode of preterm labor who will not deliver within 48 hours. However, its overall predictive ability for the identification of symptomatic and asymptomatic women at risk for preterm birth is limited. PMID- 26149830 TI - Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft. AB - Effective treatments for primary brain tumors and brain metastases represent a major unmet medical need. Targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4 and CDK6 kinase inhibitor has potential for treating primary central nervous system tumors such as glioblastoma and some peripheral tumors with high incidence of brain metastases. We compared central nervous system exposures of two orally bioavailable CDK4 and CDK6 inhibitors: abemaciclib, which is currently in advanced clinical development, and palbociclib (IBRANCE; Pfizer), which was recently approved by the U.S. Food and Drug Administration. Abemaciclib antitumor activity was assessed in subcutaneous and orthotopic glioma models alone and in combination with standard of care temozolomide (TMZ). Both inhibitors were substrates for xenobiotic efflux transporters P-glycoprotein and breast cancer resistant protein expressed at the blood-brain barrier. Brain Kp,uu values were less than 0.2 after an equimolar intravenous dose indicative of active efflux but were approximately 10-fold greater for abemaciclib than palbociclib. Kp,uu increased 2.8- and 21-fold, respectively, when similarly dosed in P-gp-deficient mice. Abemaciclib had brain area under the curve (0-24 hours) Kp,uu values of 0.03 in mice and 0.11 in rats after a 30 mg/kg p.o. dose. Orally dosed abemaciclib significantly increased survival in a rat orthotopic U87MG xenograft model compared with vehicle-treated animals, and efficacy coincided with a dose-dependent increase in unbound plasma and brain exposures in excess of the CDK4 and CDK6 Ki values. Abemaciclib increased survival time of intracranial U87MG tumor-bearing rats similar to TMZ, and the combination of abemaciclib and TMZ was additive or greater than additive. These data show that abemaciclib crosses the blood-brain barrier and confirm that both CDK4 and CDK6 inhibitors reach unbound brain levels in rodents that are expected to produce enzyme inhibition; however, abemaciclib brain levels are reached more efficiently at presumably lower doses than palbociclib and are potentially on target for a longer period of time. PMID- 26149831 TI - Public knowledge about dementia in Germany--results of a population survey. AB - OBJECTIVES: The following research questions are addressed: (1) What does the German public know about dementia? (2) Are social factors, care experience and contact with dementia patients associated with knowledge about dementia? (3) Is knowledge associated with attitudes/beliefs about dementia? METHODS: Analyses are based on a German mail survey conducted in 2012. Sample consists of persons aged 18-79 years. 1795 persons filled out the questionnaire (response rate 78 %). Respondents were asked about their knowledge of and attitudes about dementia. RESULTS: Knowledge about cause, prevention, diagnosis, treatment and life impact of dementia is characterized by a relatively high uncertainty. People with care experiences and people from higher status groups know more about dementia. People with more knowledge are less likely to believe that dementia patients have a high quality of life, but tend to be less skeptical about early detection of dementia. CONCLUSIONS: To increase knowledge, reduce uncertainty and modify attitudes towards dementia and those who are afflicted, educational programs and contact based approaches should be considered. PMID- 26149832 TI - Augmented reality visualization of deformable tubular structures for surgical simulation. AB - BACKGROUND: Surgical simulation based on augmented reality (AR), mixing the benefits of physical and virtual simulation, represents a step forward in surgical training. However, available systems are unable to update the virtual anatomy following deformations impressed on actual anatomy. METHODS: A proof-of concept solution is described providing AR visualization of hidden deformable tubular structures using nitinol tubes sensorized with electromagnetic sensors. This system was tested in vitro on a setup comprised of sensorized cystic, left and right hepatic, and proper hepatic arteries. In the trial session, the surgeon deformed the tubular structures with surgical forceps in 10 positions. RESULTS: The mean, standard deviation, and maximum misalignment between virtual and real arteries were 0.35, 0.22, and 0.99 mm, respectively. CONCLUSION: The alignment accuracy obtained demonstrates the feasibility of the approach, which can be adopted in advanced AR simulations, in particular as an aid to the identification and isolation of tubular structures. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26149833 TI - Contrasting impacts of continuous moderate drought and episodic severe droughts on the aboveground-biomass increment and litterfall of three coexisting Mediterranean woody species. AB - Climate change is predicted to increase the aridity in the Mediterranean Basin and severely affect forest productivity and composition. The responses of forests to different timescales of drought, however, are still poorly understood because extreme and persistent moderate droughts can produce nonlinear responses in plants. We conducted a rainfall-manipulation experiment in a Mediterranean forest dominated by Quercus ilex, Phillyrea latifolia, and Arbutus unedo in the Prades Mountains in southern Catalonia from 1999 to 2014. The experimental drought significantly decreased forest aboveground-biomass increment (ABI), tended to increase the litterfall, and decreased aboveground net primary production throughout the 15 years of the study. The responses to the experimental drought were highly species-specific. A. unedo suffered a significant reduction in ABI, Q. ilex experienced a decrease during the early experiment (1999-2003) and in the extreme droughts of 2005-2006 and 2011-2012, and P. latifolia was unaffected by the treatment. The drought treatment significantly increased branch litterfall, especially in the extremely dry year of 2011, and also increased overall leaf litterfall. The drought treatment reduced the fruit production of Q. ilex, which affected seedling recruitment. The ABIs of all species were highly correlated with SPEI in early spring, whereas the branch litterfalls were better correlated with summer SPEIs and the leaf and fruit litterfalls were better correlated with autumn SPEIs. These species-specific responses indicated that the dominant species (Q. ilex) could be partially replaced by the drought-resistant species (P. latifolia). However, the results of this long-term study also suggest that the effect of drought treatment has been dampened over time, probably due to a combination of demographic compensation, morphological and physiological acclimation, and epigenetic changes. However, the structure of community (e.g., species composition, dominance, and stand density) may be reordered when a certain drought threshold is reached. PMID- 26149834 TI - Identification of translational dermatology research priorities in the U.K.: results of an electronic Delphi exercise. AB - BACKGROUND: Translational research is the direct application of basic and applied research to patient care. It is estimated that there are at least 2000 different skin diseases; thus, there are considerable challenges in seeking to undertake research on each of these disorders. OBJECTIVES: This electronic Delphi (e Delphi) exercise was conducted in order to generate a list of translational dermatology research questions that are regarded as a priority for further investigations. METHODS: During the first phase of the e-Delphi exercise, 228 research questions were generated by an expert panel that included clinical academic dermatologists, clinical dermatologists, nonclinical scientists, dermatology trainees and representatives from patient support groups. RESULTS: Following completion of the second and third phases, 40 questions on inflammatory skin disease, 20 questions on structural skin disorders/genodermatoses, 37 questions on skin cancer and eight miscellaneous questions were designated as priority translational dermatology research questions (PRQs). In addition to PRQs on a variety of disease areas (including multiple PRQs on psoriasis, eczema, squamous cell carcinoma and melanoma), there were a number of cross-cutting themes that identified a need to investigate mechanisms/pathogenesis of disease and the necessity to improve treatments for patients with skin disease. CONCLUSIONS: It is predicted that this list of PRQs will help to provide a strategic direction for translational dermatology research in the U.K. and that addressing this list of questions will ultimately provide clinical benefit for substantial numbers of patients with skin disorders. PMID- 26149836 TI - Chronic kidney disease: Metformin increases risk of mortality in patients with advanced chronic kidney disease. PMID- 26149837 TI - Risk factors: The kidneys find a voice in cardiovascular risk prediction. PMID- 26149835 TI - Amplifying renal immunity: the role of antimicrobial peptides in pyelonephritis. AB - Urinary tract infections (UTIs), including pyelonephritis, are among the most common and serious infections encountered in nephrology practice. UTI risk is increased in selected patient populations with renal and urinary tract disorders. As the prevalence of antibiotic-resistant uropathogens increases, novel and alternative treatment options will be needed to reduce UTI-associated morbidity. Discoveries over the past decade demonstrate a fundamental role for the innate immune system in protecting the urothelium from bacterial challenge. Antimicrobial peptides, an integral component of this urothelial innate immune system, demonstrate potent bactericidal activity toward uropathogens and might represent a novel class of UTI therapeutics. The urothelium of the bladder and the renal epithelium secrete antimicrobial peptides into the urinary stream. In the kidney, intercalated cells--a cell-type involved in acid-base homeostasis- have been shown to be an important source of antimicrobial peptides. Intercalated cells have therefore become the focus of new investigations to explore their function during pyelonephritis and their role in maintaining urinary tract sterility. This Review provides an overview of UTI pathogenesis in the upper and lower urinary tract. We describe the role of intercalated cells and the innate immune response in preventing UTI, specifically highlighting the role of antimicrobial peptides in maintaining urinary tract sterility. PMID- 26149838 TI - Chronic kidney disease: Serious adverse effects associated with IV iron in CKD. PMID- 26149839 TI - Reply: Warfarin in patients on haemodialysis with atrial fibrillation-friend or foe? PMID- 26149840 TI - Challenging the use of warfarin in patients on dialysis with atrial fibrillation. PMID- 26149842 TI - The Association Between Bathing Habits and Severity of Atopic Dermatitis in Children. AB - BACKGROUND: Atopic dermatitis is an inflammatory skin disease that frequently affects children. The current recommendations on management using lifestyle modification are highly variable, leading to confusion and uncertainty among patients. AIM: To determine current bathing behaviors and the subsequent impact on disease severity. METHODS: This was an observational cross-sectional study conducted at an urban pediatric emergency department. Parents were asked to fill out a questionnaire concerning the patient's bathing habits. The results were correlated with the atopic dermatitis severity determined by the SCORAD (SCORing Atopic Dermatitis) tool. RESULTS: No difference between variables was found to be significant for bathing frequency, time spent bathing, or use of moisturizers. Multivariate analysis showed that atopic dermatitis severity increased with age greater than 2 years (P = .0004) and with greater bathing duration (P = .001). CONCLUSION: Atopic dermatitis severity may be associated with a longer duration of bathing. The frequency of bathing does not appear to affect atopic dermatitis severity. PMID- 26149843 TI - Outpatient Management of Febrile Children With Sickle Cell Disease. AB - The electronic medical records at 2 children's hospitals were reviewed from June 1, 2011 to May 31, 2013 for all patients with sickle cell disease who presented with fever. Of a total of 390 blood cultures drawn, 11 cultures (2.8%) turned positive with only 1 (0.3%) growing a true pathogen. This culture turned positive in 13 hours. There were 154 patients who received exclusive outpatient management of fever. Fourteen patients (9.1%) completed 1 acute care visit, 16 patients (10.4%) completed 2 acute care visits, and 124 patients (80.5%) completed 3 acute care visits. Of those treated exclusively as outpatients, there was 1 positive culture that was considered a contaminant. Although the overall rate of positivity was low, this study confirms previous findings that pediatric blood cultures become positive with pathogens within 48 hours. Given the high rate of compliance and early time to positivity of true pathogens, we suggest that follow up for the febrile sickle cell disease patients can be treated on an outpatient basis. PMID- 26149841 TI - Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial. AB - BACKGROUND: Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. METHODS: We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged >=12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs >=70%), age (<18 vs >=18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. FINDINGS: Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment attributable adverse events between groups. INTERPRETATION: Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials. FUNDING: Medical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Programme. PMID- 26149844 TI - Risk Factors for Attention and Behavioral Issues in Pediatric Sickle Cell Disease. AB - BACKGROUND: Children with sickle cell disease have an increased risk of neurodevelopmental disorders such as attention deficit hyperactivity disorder, intellectual disability, and specific learning disabilities. Little research has been done to characterize the sickle cell disease-related characteristics associated with neurodevelopmental disorders in the sickle cell disease population. METHODS: This study was a retrospective chart review involving the outpatient records of 2 medical centers, Kennedy Krieger Institute and Johns Hopkins Hospital. Participants in the study included 59 children with sickle cell disease with a documented neurodevelopmental diagnosis, specifically attention deficit hyperactivity disorder, attention issues, behavioral issues, executive dysfunction, specific learning disabilities in math, reading, and reading comprehension, intellectual disabilities, developmental delay, fine motor disorders, language disorders, or autism spectrum disorders. RESULTS: Children with sickle cell disease type hemoglobin S-beta thalassemia plus had significantly higher odds of attention issues than children with sickle cell disease type hemoglobin SS (OR = 17.0, 95% CI = 1.99-145.00, P < .02). Children with sickle cell disease and a reported history of asthma had significantly higher odds of behavioral issues than children with sickle cell disease without a history of asthma, after adjustment for gender and sickle cell disease type (exact OR = 19.53, 95% CI = 1.16-1369.72, P < .04). CONCLUSION: Children with sickle cell disease may have increased risk for certain neurodevelopmental diagnoses based on their disease characteristics and associated comorbidities. These preliminary study results should be explored in a larger database. PMID- 26149845 TI - Fever, Genital Pain, and Genital Ulcers. PMID- 26149846 TI - Screening for Celiac Disease in a Pediatric Primary Care Setting. AB - Celiac disease (CD) is an autoimmune enteropathy in genetically predisposed individuals triggered by the ingestion of gluten. The prevalence in adults in the United States is increasing. Despite recognition of asymptomatic patients that benefit from screening and improved diagnostics, the majority of patients remain undiagnosed. The purpose of this study is to determine the prevalence of CD in at risk and not-at-risk pediatric patients in a primary care practice routinely screening for CD. The records of 2325 pediatric patients who underwent serological testing with immunoglobulin A tissue transglutaminase (tTG) during a 5-year period were reviewed. Patients were categorized as at-risk or not-at-risk for CD. The prevalence of CD in at-risk patients was 1:26, the prevalence of CD in not-at-risk patients was 1:111. Our results suggest that the prevalence of CD in children approximates that of US adults and that the true prevalence in children without known risk factors may be increasing. PMID- 26149847 TI - Recurrent Cyclic Vomiting in Adolescents: Can It Be Cannabinoid Hyperemesis Syndrome? PMID- 26149848 TI - Autism Speaks Toolkits: Resources for Busy Physicians. AB - Given the increased prevalence of autism spectrum disorders (ASD), it is likely that busy primary care providers (PCP) are providing care to individuals with ASD in their practice. Autism Speaks provides a wealth of educational, medical, and treatment/intervention information resources for PCPs and families, including at least 32 toolkits. This article serves to familiarize PCPs and families on the different toolkits that are available on the Autism Speaks website. This article is intended to increase physicians' knowledge on the issues that families with children with ASD frequently encounter, to increase their ability to share evidence-based information to guide treatment and care for affected families in their practice. PMID- 26149849 TI - Types of Infant Formulas Consumed in the United States. AB - We examined consumption of different types of infant formula (eg, cow's milk, soy, gentle/lactose-reduced, and specialty) and regular milk among a nationally representative sample of 1864 infants, 0 to 12 months old, from the National Health and Nutrition Examination Survey, 2003-2010. Among the 81% of infants who were fed formula or regular milk, 69% consumed cow's milk formula, 12% consumed soy formula, 5% consumed gentle/ lactose-reduced formulas, 6% consumed specialty formulas, and 13% consumed regular milk products. There were differences by household education and income in the percentage of infants consuming cow's milk formula and regular milk products. The majority of infants in the United States who were fed formula or regular milk consumed cow's milk formula (69%), with lower percentages receiving soy, specialty, gentle/sensitive, or lactose free/reduced formulas. Contrary to national recommendations, 13% of infants younger than 1 year consumed regular milk, and the percentage varied by household education and income levels. PMID- 26149850 TI - Report of Sugar-Sweetened Beverages Offered in Pennsylvania Childcare Centers. AB - The study objective was to quantify sugar-sweetened beverage (SSB) offerings to children in Pennsylvania (PA) childcare centers and determine whether this information is communicated to parents. In October 2014, a SurveyMonkey link was sent to 4461 PA childcare centers. The 518 respondents represented 88% of PA counties. 279 centers (54%) serve SSBs. 330 (65%) of childcare centers provide parents a report of their child's daily intake. Of 185 centers serving SSBs and providing a daily intake report, 91% include SSB consumption. In total, 38% of centers (103/272) offer but do not report SSB consumption. In 96% of centers, parents may request their child not receive SSBs. In conclusion, though more than half of PA childcare centers surveyed offer SSBs, those providing daily intake reports usually include SSB consumption. Requiring daily intake reports may be a strategy to increase parental awareness of items consumed outside the home. PMID- 26149851 TI - Short-Term Efficacy and Correlates of Change in Health Weight Management Program for Chinese American Children. AB - A pretest and posttest study design was used to test a healthy weight management intervention with overweight and/or obese Chinese American children. Children attended 8-weekly small group sessions while parents attended a single 2-hour parent workshop. Children had their weight, height, blood pressure, waist and hip circumference, and fast lipids data assessed and completed several questions questionnaires regarding food choices, self-efficacy, and knowledge at baseline, 2 months, and 6 months. Parents completed questionnaires regarding demographic, acculturation level and family environment. We found significant reduction of body mass index, waist/hip ratio, systolic blood pressure and improvement of child's eating style, physical activity knowledge, self-efficacy, and children's quality of life at 6-month follow-up. In addition, significant improvement of high-density lipoprotein cholesterol and decrease in triglyceride were found at 6 month follow-up. Improvement of nutrition self-efficacy and decreased stimulus environment were associated with decreased body mass index in overweight and obese Chinese American children. PMID- 26149853 TI - Twenty top papers to mark The BMJ's two digital decades. PMID- 26149852 TI - Developmental profiling of gene expression in soybean trifoliate leaves and cotyledons. AB - BACKGROUND: Immediately following germination, the developing soybean seedling relies on the nutrient reserves stored in the cotyledons to sustain heterotrophic growth. During the seed filling period, developing seeds rely on the transport of nutrients from the trifoliate leaves. In soybean, both cotyledons and leaves develop the capacity for photosynthesis, and subsequently senesce and abscise once their function has ended. Before this occurs, the nutrients they contain are mobilized and transported to other parts of the plant. These processes are carefully orchestrated by genetic regulation throughout the development of the leaf or cotyledon. RESULTS: To identify genes involved in the processes of leaf or cotyledon development and senescence in soybean, we used RNA-seq to profile multiple stages of cotyledon and leaf tissues. Differentially expressed genes between stages of leaf or cotyledon development were determined, major patterns of gene expression were defined, and shared genes were identified. Over 38,000 transcripts were expressed during the course of leaf and cotyledon development. Of those transcripts, 5,000 were expressed in a tissue specific pattern. Of the genes that were differentially expressed between both later stage tissues, 90 % had the same direction of change, suggesting that the mechanisms of senescence are conserved between tissues. Analysis of the enrichment of biological functions within genes sharing common expression profiles highlights the main processes occurring within these defined temporal windows of leaf and cotyledon development. Over 1,000 genes were identified with predicted regulatory functions that may have a role in control of leaf or cotyledon senescence. CONCLUSIONS: The process of leaf and cotyledon development can be divided into distinct stages characterized by the expression of specific gene sets. The importance of the WRKY, NAC, and GRAS family transcription factors as major regulators of plant senescence is confirmed for both soybean leaf and cotyledon tissues. These results help validate functional annotation for soybean genes and promoters. PMID- 26149854 TI - Rice_Phospho 1.0: a new rice-specific SVM predictor for protein phosphorylation sites. AB - Experimentally-determined or computationally-predicted protein phosphorylation sites for distinctive species are becoming increasingly common. In this paper, we compare the predictive performance of a novel classification algorithm with different encoding schemes to develop a rice-specific protein phosphorylation site predictor. Our results imply that the combination of Amino acid occurrence Frequency with Composition of K-Spaced Amino Acid Pairs (AF-CKSAAP) provides the best description of relevant sequence features that surround a phosphorylation site. A support vector machine (SVM) using AF-CKSAAP achieves the best performance in classifying rice protein phophorylation sites when compared to the other algorithms. We have used SVM with AF-CKSAAP to construct a rice-specific protein phosphorylation sites predictor, Rice_Phospho 1.0 (http://bioinformatics.fafu.edu.cn/rice_phospho1.0). We measure the Accuracy (ACC) and Matthews Correlation Coefficient (MCC) of Rice_Phospho 1.0 to be 82.0% and 0.64, significantly higher than those measures for other predictors such as Scansite, Musite, PlantPhos and PhosphoRice. Rice_Phospho 1.0 also successfully predicted the experimentally identified phosphorylation sites in LOC_Os03g51600.1, a protein sequence which did not appear in the training dataset. In summary, Rice_phospho 1.0 outputs reliable predictions of protein phosphorylation sites in rice, and will serve as a useful tool to the community. PMID- 26149855 TI - Transformation of external sulphate and its effect on phosphorus mobilization in Lake Moshui, Wuhan, China. AB - Average concentrations of sulphate in lakes continue to increase sharply. The response of phosphorus to sulphate input is of great importance due to the relationship between eutrophication and ecological health. A four-week experiment was conducted under simulated conditions using samples from a heavily polluted lake, Lake Moshui, in Wuhan, China, to examine the influence of external sulphate on phosphorus release and the transformation of sulphate. The results showed that the diffusion of sulphate into the sediments promoted the proliferation of sulphate-reducing bacteria (SRB) and the reduction of sulphate. Acetic acid was consumed due to sulphate reduction. The soluble reactive phosphorus (SRP) and soluble Fe measured with diffusive equilibration in thin-films (DET) probes increased significantly after the input of sulphate. The content of SRP was consistent with the variation in both the SRB number and the S(0) content in the sediments. The maximum SRP concentration of 100.43 mg L(-1) was recorded 3 cm below the sediment-water interface on the 29th d, which was more than twice the value of the control. There was a positive correlation between concentrations of Fe and SRP in the overlying water and the pore water of the sediments. PMID- 26149856 TI - Influence of Typha domingensis in the removal of high P concentrations from water. AB - A greenhouse experiment was conducted to evaluate the removal of high P concentration from water by vegetated and unvegetated wetlands. Reactors containing 4 kg of sediment and two plants of Typha domingensis (vegetated treatments) and reactors containing only sediment (unvegetated treatments) were arranged. Reactors were dosed with 100 and 500 mg L(-1) of P-PO4. The studied concentrations tried to simulate an accidental dump. Controls without P addition were also disposed. Water samples were collected periodically and analyzed for phosphorus. Sediment (0-3 (surface), 3-7 (medium) and 7-10 cm (deep)) and plant samples (roots, rhizomes, submerged leaves and aerial leaves) were collected at the beginning and at end of the experiment and were analyzed for total phosphorus. P fractionation was performed in the surface sediment layer. Relative growth rate (RGR) was calculated in each treatment considering initial and final plant height. P was efficiently removed from water in both, vegetated and unvegetated treatments. However, the major P removal was achieved in vegetated treatments. T. domingensis has a high capacity to tolerate and accumulate high P concentrations, especially in leaves, causing P accumulation in sediment to be significantly low in vegetated treatments. P accumulation was produced in the surface sediment layer (0-3 cm) in all treatments, mainly retained as iron-bound P. Present results point the large removal capacity of phosphate of systems planted with T. domingensis. Therefore T. domingensis is suitable for phytoremediation practice, being capable to tolerate high P concentration. PMID- 26149857 TI - Molecular dynamic simulation of asphaltene co-aggregation with humic acid during oil spill. AB - Humic acid in water and sediment plays a key role in the fate and transport of the spilled oil, but little is known about its influence on the aggregation of heavy oil asphaltenes which is adverse for remediation. Molecular dynamic simulation was performed to characterize the co-aggregation of asphaltenes (continental model and Violanthrone-79 model) with Leonardite humic acid (LHA) at the toluene-water interface and in bulk water, respectively, to simulate the transport of asphaltenes from oil to water. At the toluene-water interface, a LHA layer tended to form and bind to the water by hydrogen bonding which provided a surface for the accumulation of asphaltenes by parallel or T-shape stacking. After entering the bulk water, asphaltene aggregates stacked in parallel were tightly sequestrated inside the inner cavity of LHA aggregates following surface adsorption and structure deformation. Asphaltene aggregation in water was 2-fold higher than at the toluene-water interface. The presence of LHA increased the intensity of asphaltene aggregation by up to 83% in bulk water while relatively less influence was observed at the toluene-water interface. Overall results suggested that the co-aggregation of asphaltene with humic acid should be incorporated to the current oil spill models for better interpreting the overall environmental risks of oil spill. PMID- 26149858 TI - Genetic susceptibility factors for alcohol-induced chronic pancreatitis. AB - Chronic pancreatitis is a progressive inflammatory disease of the pancreas and frequently associated with immoderate alcohol consumption. Since only a small proportion of alcoholics eventually develop chronic pancreatitis genetic susceptibility factors have long been suspected to contribute to the pathogenesis of the disease. Smaller studies in ethnically defined populations have found that not only polymorphism in proteins involved in the metabolism of ethanol, such as Alcohol Dehydrogenase and Aldehyde Dehydrogenase, can confer a risk for developing chronic pancreatitis but also mutations that had previously been reported in association with idiopathic pancreatitis, such as SPINK1 mutations. In a much broader approach employing genome wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-induced pancreatitis. These results from North America have now been confirmed by a European consortium. In another genome wide approach polymorphisms in the genes encoding Fucosyltransferase 2 (FUT2) non-secretor status and blood group B were not only found in association with higher serum lipase levels in healthy volunteers but also to more than double the risk for developing alcohol-associated chronic pancreatitis. These novel genetic associations will allow to investigate the pathophysiological and biochemical basis of alcohol-induced chronic pancreatitis on a cellular level and in much more detail than previously possible. PMID- 26149859 TI - Causes of Fever in Rural Southern Laos. AB - The etiology of fever in rural Lao People's Democratic Republic (Laos) has remained obscure until recently owing to the lack of laboratory facilities. We conducted a study to determine the causes of fever among 229 patients without malaria in Savannakhet Province, southern Laos; 52% had evidence of at least one diagnosis (45% with single and 7% with apparent multiple infections). Among patients with only one diagnosis, dengue (30.1%) was the most common, followed by leptospirosis (7.0%), Japanese encephalitis virus infection (3.5%), scrub typhus (2.6%), spotted fever group infection (0.9%), unspecified flavivirus infection (0.9%), and murine typhus (0.4%). We discuss the empirical treatment of fever in relation to these findings. PMID- 26149860 TI - Genome-Scale Protein Microarray Comparison of Human Antibody Responses in Plasmodium vivax Relapse and Reinfection. AB - Large scale antibody responses in Plasmodium vivax malaria remains unexplored in the endemic setting. Protein microarray analysis of asexual-stage P. vivax was used to identify antigens recognized in sera from residents of hypoendemic Peruvian Amazon. Over 24 months, of 106 participants, 91 had two symptomatic P. vivax malaria episodes, 11 had three episodes, 3 had four episodes, and 1 had five episodes. Plasmodium vivax relapse was distinguished from reinfection by a merozoite surface protein-3alpha restriction fragment length polymorphism polymerase chain reaction (MSP3alpha PCR-RFLP) assay. Notably, P. vivax reinfection subjects did not have higher reactivity to the entire set of recognized P. vivax blood-stage antigens than relapse subjects, regardless of the number of malaria episodes. The most highly recognized P. vivax proteins were MSP 4, 7, 8, and 10 (PVX_003775, PVX_082650, PVX_097625, and PVX_114145); sexual stage antigen s16 (PVX_000930); early transcribed membrane protein (PVX_090230); tryptophan-rich antigen (Pv-fam-a) (PVX_092995); apical merozoite antigen 1 (PVX_092275); and proteins of unknown function (PVX_081830, PVX_117680, PVX_118705, PVX_121935, PVX_097730, PVX_110935, PVX_115450, and PVX_082475). Genes encoding reactive proteins exhibited a significant enrichment of non synonymous nucleotide variation, an observation suggesting immune selection. These data identify candidates for seroepidemiological tools to support malaria elimination efforts in P. vivax-endemic regions. PMID- 26149861 TI - Quantification of Human Norovirus GII on Hands of Mothers with Children Under the Age of Five Years in Bagamoyo, Tanzania. AB - Human noroviruses are the most common cause of viral gastroenteritis worldwide and one of the leading causes of viral diarrhea in children under the age of 5 years. Hands have been shown to play an important role in norovirus transmission. Norovirus outbreaks tend to exhibit strong seasonality, most often occurring during cold, dry months, but recently have also been documented during hot, dry winter months in the southern hemisphere. Other research suggests that rainfall is an important factor in norovirus outbreaks. This study examines the prevalence and concentration of human norovirus GII on the hands of mothers in Bagamoyo, Tanzania, during the rainy and dry seasons. Norovirus GII was detected in approximately 5% of hand rinse samples during both the rainy and dry seasons. Fecal indicator bacteria levels, Escherichia coli and enterococci, in hand rinse samples were not associated with norovirus hand contamination. Turbidity of the hand rinses was found to be associated with norovirus presence on mothers' hands; however, this relationship was only observed during the rainy season. The results suggest mothers' hands serve as a source of norovirus exposure for young children in Tanzanian households, and further work is needed to determine better indicators of norovirus contamination in these environments. PMID- 26149862 TI - Safety and Immunogenicity of a Dengue Virus Serotype-1 Purified-Inactivated Vaccine: Results of a Phase 1 Clinical Trial. AB - We describe the results from a human clinical trial of a dengue virus serotype-1, purified-inactivated vaccine (DENV-1 PIV) adjuvanted with aluminum hydroxide. This first-in-man, Phase 1, open-label clinical trial consisted of two groups of flavivirus-naive healthy adult volunteers that received two intramuscular vaccine doses of either 2.5 MUg or 5 MUg of DENV-1 PIV administered on days 0 and 28. Following vaccination, both vaccine doses exhibited an acceptable safety profile with minimal injection site and systemic reactions. By study day 42, 2 weeks following the second vaccine dose, all volunteers in both vaccine groups developed serum-neutralizing antibodies against DENV-1. Additional testing using an enzyme-linked immunosorbent assay demonstrated induction of a humoral immune response following both vaccine doses. The DENV-1 PIV was safe and immunogenic in a small number of volunteers supporting development and further testing of a tetravalent DENV PIV formulation. PMID- 26149863 TI - Concurrent Pneumonia in Children Under 5 Years of Age Presenting to a Diarrheal Hospital in Dhaka, Bangladesh. AB - Respiratory and gastrointestinal infections are the top killers of children worldwide, and their co-occurrence is reported but not well understood. Our aim was to determine the risk factors for concurrent presentation of diarrhea and pneumonia (DP) in a resource-limited setting in Bangladesh. We used data from the Diarrheal Disease Surveillance System of the icddr,b Dhaka Hospital to identify children < 60 months of age with diarrhea and concurrent pneumonia, defined as a history of cough, an abnormal lung examination, and tachypnea. For the years 1996 2007, out of total 14,628 diarrheal patients surveyed, there were 607 (4%) patients who satisfied criteria for pneumonia. Those with DP had a higher mortality rate (4% versus 0.05%, odds ratio [OR] = 86, 95% confidence interval [CI] = 26-286) and a longer hospital stay (mean 84 versus 26 hours, difference 58 hours, 95% CI = 52-64 hours) than those with diarrhea (D) only. In multivariable logistic regression comparing cases (N = 607) with controls matched for month and year of admission at a ratio of 1:3 (N = 1,808), we found that DP was associated with younger age, male gender, severe acute malnutrition (SAM), less maternal education, lower family income, and lack of current breast-feeding history. PMID- 26149864 TI - Characterization of Leishmania (Leishmania) waltoni n.sp. (Kinetoplastida: Trypanosomatidae), the Parasite Responsible for Diffuse Cutaneous Leishmaniasis in the Dominican Republic. AB - Leishmania parasites isolated, between 1979 and 1988 by the late Bryce Walton, from Dominican Republic (DR) patients with diffuse cutaneous leishmaniasis, were characterized using a panel of 12 isoenzymes, 23 monoclonal antibodies, small subunit ribosomal DNA (SSu rDNA), and multilocus sequence analysis (MLSA). The isoenzyme and monoclonal antibody profiles and the MLSA results showed that the Dominican Republic parasites were distinct from other described Leishmania species. This new species belongs to the mexicana complex, which is distributed in central and parts of northern South America. It is suggested that the parasites uniqueness from other members of the mexicana complex is related to it being isolated on an island for millions of years. If Leishmania (Leishmania) waltoni fails to adapt to some imported mammal, such as the house rat, it will be the only Leishmania to be classified as an endangered species. The excessive destruction of habitats on Hispaniola threatens the survival of its vectors and presumed natural reservoirs, such as the rodent hutias and the small insectivorous mammal solenodon. The concept of Leishmania species is discussed in the light of recent evaluations on criteria for defining bacterial species. PMID- 26149865 TI - Two Generations of "Gold Standards": The Impact of a Decade in Hepatitis E Virus Testing Innovation on Population Seroprevalence. AB - Hepatitis E virus (HEV) is a global pathogen responsible for approximately 20 million infections every year in developing countries, yet remains under recognized. In this population-based cohort study, 1,025 randomly selected participants were enrolled from Matlab, Bangladesh (2004-2005). All participants were tested for HEV antibodies and total immunoglobulin (Ig), using an in-house enzyme immunoassay developed by Walter Reed Army Institute of Research (WRAIR). In 2014, we retested the banked sera of 1,009 of those participants using the Wantai anti-HEV IgG enzyme-linked immunosorbent assay (ELISA). The WRAIR assay estimated the overall population seroprevalence as 26.6% (95% confidence interval [CI]: 24.0, 29.5), whereas the Wantai assay produced significantly higher estimated seroprevalence, 46.7% (95% CI: 43.5-49.8) (P < 0.001). However, the two tests give nearly identical findings in those 5 years and under (N = 94) with a 98% agreement between the tests. Retesting populations with modern assays is necessary to establish better population-level estimates of disease burden. PMID- 26149867 TI - Mosquitoes of Anopheles hyrcanus (Diptera, Culicidae) Group: Species Diagnostic and Phylogenetic Relationships. AB - Herein, we report the results of study of Anopheles species in Primorsk and Khabarovsk regions of Russia. Three species of the Anopheles hyrcanus group: An. kleini, An. pullus, and An. lesteri were identified by molecular taxonomic diagnostics for the first time in Russia. Surprisingly, An. sinensis, which earlier was considered the only species of Anopheles in Russian Far East, was not observed. We analyzed nucleotide variation in the 610-bp fragment of the 5' end of the cytochrome c oxidase subunit I (COI) region. All species possessed a distinctive set of COI sequences. A maximum likelihood phylogenetic tree was constructed for members of the hyrcanus group. The examined Anopheles hyrcanus group members could be divided into two major subgroups: subgroup 1 (An. hyrcanus and An. pullus) and subgroup 2 (An. sinensis, An. kleini, and An. lesteri), which were found to be monophyletic. PMID- 26149866 TI - A Familial Cluster of Human Brucellosis Attributable to Contact with Imported Infected Goats in Shuyang, Jiangsu Province, China, 2013. AB - Brucellosis remains a serious public health issue in developing countries, including China. On August 8, 2013, four cases of brucellosis from one extended family were reported at Shuyang County, Jiangsu Province, China. Active case finding was performed to identify the source and the risk factors of the infection and to prevent additional cases. Multiple-locus variable number tandem repeat analysis (MLVA) was used for molecular subtyping analysis. Six people from two extended families met the case definition for brucellosis infection; four were blood culture positive for Brucella melitensis biotype 3. Four additional family members were found seropositive by using a serological test. Isolates from the four patients were indistinguishable by MLVA profiling, displaying a unique type for Jiangsu Province. Field epidemiological data combined with MLVA genotyping supported a common source of the isolates from the different patients. We recommend stronger reinforcement measures for animal quarantine practices, enhanced cooperation with veterinary service organizations, and implementation of measures that strengthen public education on brucellosis to prevent further human outbreaks in Jiangsu Province. PMID- 26149868 TI - Human and Animal Fecal Contamination of Community Water Sources, Stored Drinking Water and Hands in Rural India Measured with Validated Microbial Source Tracking Assays. AB - We examined pathways of exposure to fecal contamination of human and animal origin in 24 villages in Odisha, India. In a cross-sectional study during the monsoon season, fecal exposure via community water sources (N = 123) and in the home (N = 137) was assessed using human- and nonhuman-associated Bacteroidales microbial source tracking (MST) markers and fecal coliforms (FCs). Detection rates and marker concentrations were examined to pinpoint pathways of human fecal exposure in the public and domestic domains of disease transmission in study communities. Human fecal markers were detected much more frequently in the domestic domain (45% of households) than in public domain sources (8% of ponds; 4% of groundwater drinking sources). Animal fecal markers were widely detected in both domains (74% of ponds, 96% of households, 10% of groundwater drinking sources), indicating ubiquitous risks of exposure to animal feces and zoonotic pathogens. This study confirms an often suggested contamination link from hands to stored water in the home in developing countries separately for mothers' and children's hands and both human and animal fecal contamination. In contrast to MST markers, FCs provided a poor metric to assess risks of exposure to fecal contamination of human origin in this rural setting. PMID- 26149870 TI - The importance of nurses in cancer care. PMID- 26149869 TI - Hydrogen sulfide protects spinal cord and induces autophagy via miR-30c in a rat model of spinal cord ischemia-reperfusion injury. AB - BACKGROUND: Hydrogen sulfide (H2S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the nervous system. The present study was undertaken to study the effects of exogenous H2S on ischemia/reperfusion (I/R) injury of spinal cord and the underlying mechanisms. METHODS: The effects of exogenous H2S on I/R injury were examined by using assessment of hind motor function, spinal cord infarct zone by Triphenyltetrazolium chloride (TTC) staining. Autophagy was evaluated by expressions of Microtubule associated protein 1 light chain 3 (LC3) and Beclin-1 which were determined by using Quantitative Real-Time PCR and Western blotting, respectively. RESULTS: Compared to I/R injury groups, H2S pretreatment had reduced spinal cord infarct zone, improved hind motor function in rats. Quantitative Real-Time PCR or Western blotting results showed that H2S pretreatment also downregulated miR-30c expression and upregulated Beclin-1 and LC3II expression in spinal cord. In vitro, miR-30c was showed to exert negative effect on Beclin-1 expression by targeting its 3'UTR in SY-SH-5Y cells treated with Oxygen, Glucose Deprivation (OGD). In rat model of I/R injury, pretreatment of pre-miR-30c or 3-MA (an inhibitor for autophagy) can abrogated spinal cord protective effect of H2S. CONCLUSION: H2S protects spinal cord and induces autophagy via miR-30c in a rat model of spinal cord hemia-reperfusion injury. PMID- 26149871 TI - The erosion of research integrity: the need for culture change. PMID- 26149872 TI - Artemisia: a divine dart against cancer? PMID- 26149875 TI - Transformation from NSCLC to SCLC: when did it happen? - Authors' reply. PMID- 26149876 TI - Transformation from NSCLC to SCLC: when did it happen? PMID- 26149877 TI - Taxane-related nail toxicity. PMID- 26149878 TI - Nilotinib versus imatinib for GIST - Authors' reply. PMID- 26149879 TI - Nilotinib versus imatinib for GIST. PMID- 26149880 TI - Correction to Lancet Oncol 2015; 16: e316. New scale assesses benefits of cancer medicines. PMID- 26149881 TI - Correction to Lancet Oncol 2015; 16: 738. Anti-EGFR monoclonal antibodies in lung cancer treatment. PMID- 26149882 TI - Correction to Lancet Oncol 2015; 16: 747. EGFR mutations and EGFR tyrosine kinase inhibitors. PMID- 26149883 TI - Correction to Lancet Oncol 2015; 16: e227. Primary endpoints for future prophylactic human papillomavirus vaccine trials: towards infection and immunobridging. PMID- 26149884 TI - Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. AB - The management of primary CNS lymphoma is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the very few controlled studies available. In 2013, the European Association of Neuro-Oncology created a multidisciplinary task force to establish evidence-based guidelines for immunocompetent adults with primary CNS lymphoma. In this Review, we present these guidelines, which provide consensus considerations and recommendations for diagnosis, assessment, staging, and treatment of primary CNS lymphoma. Specifically, we address aspects of care related to surgery, systemic and intrathecal chemotherapy, intensive chemotherapy with autologous stem-cell transplantation, radiotherapy, intraocular manifestations, and management of elderly patients. The guidelines should aid clinicians in their daily practice and decision making, and serve as a basis for future investigations in neuro oncology. PMID- 26149885 TI - Polypharmacy in patients with advanced cancer and the role of medication discontinuation. AB - Polypharmacy is a well known problem in elderly patients in general, but its prevalence and effects in patients with cancer are less clear, particularly in end-of-life settings. This Review examines the existing literature on polypharmacy in advanced cancer and end-of-life settings by reviewing evidence based approaches to reduce polypharmacy, and outlining the potential benefits of decreasing the number of drugs that patients with cancer can take, with emphasis on the need for thoughtful discontinuation initiatives in the context of life limiting malignant disease. In view of the apparent burden of polypharmacy in patients with advanced cancer, we expect that greater attention to polypharmacy could lead to improvements in adverse drug events, cost, and possibly quality of life. However, few data for specific interventions in the advanced cancer population are available, and thus more research is warranted. PMID- 26149886 TI - Genomic alterations in lung adenocarcinoma. AB - Treatment for non-small-cell lung cancer is evolving from the use of cytotoxic chemotherapy to personalised treatment based on molecular alterations. This past decade has witnessed substantial progress in the treatment of patients with EGFR mutations and ALK rearrangements, and it is now possible to study complex genomic alterations in cancer using next-generation sequencing. Sequencing data from large-scale consortia, such as The Cancer Genome Atlas, as well as several independent groups, have helped identify novel drivers and potentially targetable alterations in lung adenocarcinomas. These data clearly suggest that lung adenocarcinoma is associated with distinct genomic alterations compared with other lung cancer subtypes, and highlight the widespread molecular heterogeneity that underlies the disease. In this Review, we discuss some of the key findings from genomic studies of lung adenocarcinoma. PMID- 26149887 TI - Recommendations for screening and early detection of common cancers in India. AB - Cancers of the breast, uterine cervix, and lip or oral cavity are three of the most common malignancies in India. Together, they account for about 34% of more than 1 million individuals diagnosed with cancer in India each year. At each of these cancer sites, tumours are detectable at early stages when they are most likely to be cured with standard treatment protocols. Recognising the key role that effective early detection and screening programmes could have in reducing the cancer burden, the Indian Institute for Cytology and Preventive Oncology, in collaboration with the US National Cancer Institute Center for Global Health, held a workshop to summarise feasible options and relevant evidence for screening and early detection of common cancers in India. The evidence-based recommendations provided in this Review are intended to act as a guide for policy makers, clinicians, and public health practitioners who are developing and implementing strategies in cancer control for the three most common cancers in India. PMID- 26149888 TI - Continued value of adjuvant anthracyclines as treatment for early breast cancer. AB - Anthracyclines are frequently used in the adjuvant treatment of early-stage breast cancer. However, with the increasing use of other active drugs--mainly taxanes and trastuzumab in HER2-positive disease--coupled with concerns about anthracycline-associated toxic effects, there is debate about whether anthracyclines are still needed. Three major factors should be taken into consideration with the investigation of the role of anthracyclines in management of early breast cancer; specifically, the proven efficacy of anthracyclines in breast cancer, the absence of superiority of non-anthracycline-based chemotherapy over anthracycline-taxane regimens, and the low risk of toxic effects associated with the cumulative doses of anthracyclines used in contemporary regimens. The risks remain substantially outweighed by the benefits of treatment with anthracyclines, and thus, they maintain an important role in adjuvant treatment of breast cancer, particularly in women with high-risk disease. PMID- 26149889 TI - Enhancing Glioblastoma-Specific Penetration by Functionalization of Nanoparticles with an Iron-Mimic Peptide Targeting Transferrin/Transferrin Receptor Complex. AB - Treatment of glioblastoma (GBM) remains to be the most formidable challenge because of the hindrance of the blood-brain barrier (BBB) along with the poor drug penetration into the glioma parenchyma. Nanoparticulate drug delivery systems (DDS) utilizing transferrin (Tf) as the targeting ligand to target the glioma-associated transferrin receptor (TfR) had met the problem of loss of specificity in biological environment due to the high level of endogenous Tf. Here we conjugated CRT peptide, an iron-mimicry moiety targeting the whole complex of Tf/TfR, to poly(ethylene glycol)-poly(l-lactic-co-glycolic acid) nanoparticles (CRT-NP), to open a new route to overcome such obstacle. High cellular associations, advanced transport ability through the BBB model, and penetration in 3-dimensional C6 glioma spheroids in vitro had preliminarily proved the advantages of CRT-NP over Tf-nanoparticle conjugates (Tf-NP). Compared with Tf-NP, NP, and Taxol, paclitaxel-loaded CRT-NP (CRT-NP-PTX) displayed a superior antiproliferation effect on C6 glioma cells and stronger inhibitory effect on glioma spheroids. Favored pharmacokinetics behavior and enhanced accumulation in glioma foci was observed, together with a much deeper distribution pattern in glioma parenchyma compared with unmodified nanoparticles and Tf-NP. Eventually, mice treated with CRT-NP-PTX showed a remarkably prolonged median survival compared to those treated with Taxol, NP, or Tf-NP. In conclusion, the modification of CRT to nanoparticles holds great promise for enhancement of antiglioma therapy. PMID- 26149890 TI - Comorbidity and the risk of venous thromboembolism in prostate cancer. PMID- 26149891 TI - A Simple Synthesis of Triangular All-Metal Aromatics Allowing Access to Isolobal All-Metal Heteroaromatics. AB - A simple synthetic method allows the one-pot assembly of C3 -symmetric, 44-core valence-electron, triangular Pd or Pt clusters and their heterobimetallic mixed Pd/Pt analogues. These mixed metal complexes are the first examples of stable triangular all-metal heteroaromatics. In contrast to traditional heteroaromatic molecules formed combining main-group elements, they actually retain structural and electronic features of their homonuclear analogues. PMID- 26149892 TI - Phase coherence of auditory steady-state response reflects the amount of cognitive workload in a modified N-back task. AB - The auditory steady-state response (ASSR) is an oscillatory brain activity evoked by repetitive auditory stimuli. Previous studies have reported that the power and phase locking index (PLI) of ASSR could be modulated by the degree of workload. However, those studies used different physical stimuli for tasks of differing difficulty, and the effect of the internal workload itself has not been clearly understood. In this study, we employed the modified N-back task as a visual working memory task in order to vary the degree of difficulty while keeping the physical stimulus constant. The experiment consisted of four types of tasks: No Load (NL), 1-back, 2-back, and 3-back tasks. The auditory stimulus was a 40 Hz click sound to induce ASSR. Sixteen healthy subjects participated in the present study and magnetoencephalogram responses were recorded using a 148-channel magnetometer system. The hit rate decreased and the reaction time increased according to the task difficulty. Grand averaged phase coherence activities showed the 40 Hz ASSR reductions accompanying an increase in the task difficulty even with the identical external stimuli. In particular, the phase coherence activities in 3-back task were significantly lower than that in the NL and 1-back tasks. Our results suggest that the ASSR can be a useful indicator for the amount of workload in the brain. PMID- 26149893 TI - Mnemonic discrimination relates to perforant path integrity: An ultra-high resolution diffusion tensor imaging study. AB - Pattern separation describes the orthogonalization of similar inputs into unique, non-overlapping representations. This computational process is thought to serve memory by reducing interference and to be mediated by the dentate gyrus of the hippocampus. Using ultra-high in-plane resolution diffusion tensor imaging (hrDTI) in older adults, we previously demonstrated that integrity of the perforant path, which provides input to the dentate gyrus from entorhinal cortex, was associated with mnemonic discrimination, a behavioral outcome designed to load on pattern separation. The current hrDTI study assessed the specificity of this perforant path integrity-mnemonic discrimination relationship relative to other cognitive constructs (identified using a factor analysis) and white matter tracts (hippocampal cingulum, fornix, corpus callosum) in 112 healthy adults (20 87 years). Results revealed age-related declines in integrity of the perforant path and other medial temporal lobe (MTL) tracts (hippocampal cingulum, fornix). Controlling for global effects of brain aging, perforant path integrity related only to the factor that captured mnemonic discrimination performance. Comparable integrity-mnemonic discrimination relationships were also observed for the hippocampal cingulum and fornix. Thus, whereas perforant path integrity specifically relates to mnemonic discrimination, mnemonic discrimination may be mediated by a broader MTL network. PMID- 26149895 TI - Hybrid organic-inorganic chlorozincate and a molecular zinc complex involving the in situ formed imidazo[1,5-a]pyridinium cation: serendipitous oxidative cyclization, structures and photophysical properties. AB - Two novel compounds, the organic-inorganic hybrid [L](2)[ZnCl(4)] (1) and the coordination complex LZnCl(3) (2), where L is the 2-methyl-3-(pyridin-2 yl)imidazo[1,5-a]pyridinium cation, were prepared using the oxidative condensation-cyclization of 2-pyridinecarbaldehyde and CH(3)NH(2).HCl in methanol in the presence of Zn(2+) cations. The metal-free interaction of the organic components afforded the salt [L][Cl].1.5H(2)O (3). The use of methylamine hydrochloride instead of its aqueous solution is believed to be responsible for the cyclocondensation with the formation of L instead of the expected Schiff base ligand. Compounds 1-3 have been obtained as single crystals and characterized by elemental analysis, IR, NMR spectroscopy, and single-crystal X-ray diffraction techniques. The structure of 1 is described as layers of cations and anions stacked along the c-axis, with the minimum ZnZn distance being 8.435 A inside a layer. In the crystal lattice of 3, the cations are arranged in stacks propagating along the a-axis; the 1D H-bonding polymer built of chloride ions and water molecules runs parallel to a column of stacked cations. The organic cations in salts 1 and 3 show various patterns of pi-pi stacking. The discrete molecular structure of 2 shows coordination of a Zn atom to the N(pyridyl) atom, which enables one of the chloride atoms attached to the metal centre to interact with a pi-system of the positively charged imidazolium ring. Numerous C-HCl contacts in a 1-3 are seen as space-filling van der Waals interactions of minor importance in determining crystal packing. The (1)H NMR studies suggest that the Zn-N coordination found in the solid-state structure of 2 is not retained in dmso, and 1, 2 and 3 are completely dissociated in solution. The emission spectra of 1 and 2 (lambda(max) = 455 and 445 nm, respectively) exhibit red-shifts of fluorescence wavelength when compared to 3 and differ in the shapes and maxima of the emission as well as in relative fluorescence intensity. PMID- 26149894 TI - Glycan-Dependent Neutralizing Antibodies Are Frequently Elicited in Individuals Chronically Infected with HIV-1 Clade B or C. AB - A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines. PMID- 26149896 TI - Development of a Synthetic Malonyl-CoA Sensor in Saccharomyces cerevisiae for Intracellular Metabolite Monitoring and Genetic Screening. AB - Genetic sensors capable of converting key metabolite levels to fluorescence signals enable the monitoring of intracellular compound concentrations in living cells, and emerge as an efficient tool in high-throughput genetic screening. However, the development of genetic sensors in yeasts lags far behind their development in bacteria. Here we report the design of a malonyl-CoA sensor in Saccharomyces cerevisiae using an adapted bacterial transcription factor FapR and its corresponding operator fapO to gauge intracellular malonyl-CoA levels. By combining this sensor with a genome-wide overexpression library, we identified two novel gene targets that improved intracellular malonyl-CoA concentration. We further utilized the resulting recombinant yeast strain to produce a valuable compound, 3-hydroxypropionic acid, from malonyl-CoA and enhanced its titer by 120%. Such a genetic sensor provides a powerful approach for genome-wide screening and could further improve the synthesis of a large range of chemicals derived from malonyl-CoA in yeast. PMID- 26149897 TI - Childhood obesity in New Zealand. AB - New Zealand has an unacceptably high rate of childhood obesity at 11 percent of children. The cause is due to an over consumption of food particularly in the form of junk food. To reverse this serious problem an all-of-society approach with leadership from the government is going to be required. The consequence of ignoring the problem will threaten the future viability of the health service. PMID- 26149898 TI - Effectiveness of current interventions in obese New Zealand children and adolescents. AB - AIMS: To determine the effectiveness of current interventions in New Zealand in obese children and adolescents accessing either a standard model of care (medical input alone or with the addition of dietitian and physical activity input), or one of the country's long-standing multi-disciplinary intervention programmes. METHODS: Data were recorded over approximately 2.1 years of intervention from 290 patients across four centres in New Zealand, who manage obese and overweight children and adolescents aged 3-16 years in paediatric clinics. RESULTS: There was a small but significant annual reduction in BMI SDS irrespective of the nature of intervention (-0.15 overall). There was no significant difference in BMI SDS between interventions. The extent of BMI SDS reduction decreased with increasing age at first outpatient attendance (p=0.0006). BMI SDS reduction was unaffected by ethnicity or gender. CONCLUSIONS: Mild reductions in BMI SDS are achievable in children being referred to and managed for obesity by a range of models. It is important that paediatricians are proactive in identifying and addressing obesity with families. Further research is required to evaluate multi disciplinary intervention programmes, and how their effectiveness can be increased, given their recognised benefits in improving cardiovascular and metabolic profile, as well as BMI SDS. PMID- 26149899 TI - Socioeconomic factors correlating with community antimicrobial prescribing. AB - BACKGROUND: Increasing antimicrobial resistance is a serious concern in New Zealand and worldwide. Antimicrobial resistance is tied to increased community antimicrobial consumption. Investigation of the drivers of antimicrobial prescribing in different locales is needed so that targeted interventions can be devised. Counties Manukau District Health Board (CMDHB) serves a diverse, relatively socio-economically deprived population that has the highest rate of community antimicrobial prescribing in New Zealand. We hypothesise that socio economic factors are important in determining much of the prescribing of antimicrobials in the CMDHB population. METHODS: We collected data on the number of antibacterial prescriptions per person in each pre-defined geographical Area Unit in the CMDHB community in 2013, and compared these with demographic and socioeconomic parameters collected in the 2013 New Zealand census. Simple and multiple linear regression analyses were used to identify factors that correlated with antimicrobial prescribing. RESULTS: Multiple regression analysis showed that antimicrobial prescribing was strongly associated with a higher ratio of number of people to bedrooms in a dwelling (an index of crowding), with some added association with Maori ethnicity. When these factors were accounted for, there was no significant added influence from a range of other factors such as income, smoking or educational qualifications. CONCLUSIONS: Antimicrobial prescribing may be influenced by different factors within different communities. It is important to target the determinants of antimicrobial prescribing when addressing the issue of high community antimicrobial consumption. In the CMDHB community, crowding in homes is associated with higher rates of antimicrobial prescribing. This association may be because crowding directly increases infection rates, or that crowding serves as a proxy for other factors yet to be identified. Further investigation of the determinants of antimicrobial prescribing is needed. PMID- 26149900 TI - An audit on the appropriate use of faecal calprotectin testing within the Taranaki DHB: a case for a more discerning approach. AB - AIMS: Faecal calprotectin (FC) is a recognised marker for excluding inflammatory bowel disease (IBD). However, it is often not used appropriately. This audit aimed to identify the rate of its use of in Taranaki, along with attempting to assess how appropriately it is used and overall utility. METHODS: A list of FCs performed in Taranaki from July 2013 to December 2013 was obtained. Notes were examined, identifying the indication, its outcome, and a decision made whether or not the test added any benefit. RESULTS: 206 patients were identified. A large number (n=75) were excluded due to inadequate clinical information. Of the remaining 131 patients, 37% (n=49) did not benefit. 22% (n=29) avoided further investigation with a negative result. 91% of patients with previously known IBD avoided invasive investigation with a negative result. There was a strong correlation between very high levels (>500 mg/g) and a diagnosis of IBD (88%), as well as a strong correlation between lower levels (<200mg/g) and excluding IBD (86%). CONCLUSIONS: FC remains useful to exclude IBD, and can assist in patients with established disease. However, in a significant percentage, the test adds no value. The absolute level of FC may also assist diagnosis. More research is needed, and more education is recommended. PMID- 26149901 TI - Inequities in provision of seizure care across the Wellington Region. AB - AIM: We wanted to determine whether adult patients presenting with a seizure to the emergency department (ED) of Wellington Hospital and Hutt Hospital, in the Wellington region, were equally likely to be referred for neurology input. METHODS: A retrospective review was conducted of 250 consecutive patients presenting with a seizure to the ED of each hospital. Patient electronic records were examined to determine the proportion of patients discussed with the inpatient neurology team and referred to neurology outpatient clinic. RESULTS: Fifty-two per cent of the patients presenting to Wellington Hospital ED with a seizure were referred to neurology, compared to 13.4% of those presenting to Hutt Hospital ED. The proportion of 'first seizure' patients referred to neurology was 63.1% for Wellington Hospital and 9.8% for Hutt Hospital. The difference in referral rates was primarily attributable to the difference in inpatient referrals. Maori were over-represented in the patients presenting to ED with a seizure, compared to their population composition. CONCLUSIONS: This study demonstrated unequal referral practices and therefore provision of neurology care for adult seizure patients across the Wellington region, for patients with established epilepsy and those with a first seizure. There were a disproportionately high number of Maori accessing acute seizure care. PMID- 26149902 TI - Getting serious about protecting New Zealand children against unhealthy food marketing. AB - Reducing childhood obesity is now a high priority for Government and New Zealand society, and foremost in these efforts should be getting serious about protecting children from being targeted by sophisticated marketing for the very foods and beverages that are making them fat. The marketing of unhealthy food products to children is powerful, pervasive and predatory. Previous studies in New Zealand found that food marketing targeted at children through various media is predominantly for unhealthy food products. Statutory comprehensive regulations providing full protections for children against unhealthy food marketing are recommended, but strengthening voluntary codes into a more quasi-regulatory system would allow food companies to clearly demonstrate their commitments to becoming part of the solution for New Zealand's unacceptably high rate of childhood obesity. PMID- 26149903 TI - Clinical governance and point-of-care testing at health provider level. AB - Clinical governance provides a quality assurance and safety framework. A large proportion of point-of-care testing (POCT) activities in New Zealand are not subject to the same levels of regulation and accreditation that must be met by conventional medical laboratory testing. Providers who use POCT for diagnosis, monitoring and treatment need to develop programmes that are subject to effective clinical governance to ensure that POCT devices are suitable and safe for the clinical setting in which they are being used, and test results are consistently accurate and precise, ie reliable, at all times. POCT needs to be integrated with clinical management protocols and test results need to be accessible to healthcare personnel. Effective clinical governance of POCT by providers requires recognition by top management that the scale and scope of testing within New Zealand is large and expanding, and that there are associated risks and costs. Systematic input from laboratory, clinical and managerial stakeholders, and compliance with guidelines and standards is required to ensure that POCT is safe, clinically justified and cost effective. PMID- 26149904 TI - Standardised (plain) packaging: the time for implementation has come. AB - Although a growing number of countries have passed legislation to introduce standardised (or 'plain') packaging, New Zealand's legislation is currently stalled. The research evidence supporting standardised packaging is strong. Furthermore, evaluations from Australia, the first country to introduce this measure, show standardised packaging is reducing the appeal of smoking. Tobacco consumption in Australia has also fallen since the introduction of standardised packaging. The government should reassert its commitment to New Zealand's Smokefree 2025 goal by recognising the Australian evidence and passing and implementing standardised packaging as soon as possible. PMID- 26149905 TI - Reversible diabetes insipidus in a patient with multiple myeloma. PMID- 26149906 TI - Oculosympathetic paresis. PMID- 26149907 TI - Re: Physician-assisted dying--a survey of Waikato general practitioners. PMID- 26149908 TI - Electronic cigarettes appealing quit aids for young adult smokers. PMID- 26149909 TI - Seasonal variability in sepsis hospitalisations. PMID- 26149910 TI - Trends in medical student research and publishing. PMID- 26149911 TI - The incidence of acute rheumatic fever in New Zealand, 2010-2013. PMID- 26149912 TI - Modeling and estimation of production rate for the production phase of non-growth associated high cell density processes. AB - This paper addresses the estimation of the specific production rate of intracellular products and the modeling of the bioreactor volume dynamics in high cell density fed-batch reactors. In particular, a new model for the bioreactor volume is proposed, suitable to be used in high cell density cultures where large amounts of intracellular products are stored. Based on the proposed volume model, two forms of a high-order sliding mode observer are proposed. Each form corresponds to the cases with residual biomass concentration or volume measurement, respectively. The observers achieve finite time convergence and robustness to process uncertainties as the kinetic model is not required. Stability proofs for the proposed observer are given. The observer algorithm is assessed numerically and experimentally. PMID- 26149913 TI - TNF-alpha-induced programmed cell death in the pathogenesis of acquired aplastic anemia. AB - The mechanism of acquired aplastic anemia (AA), a bone marrow hematopoiesis failure disease, has not been fully understood. TNF-alpha is a pleiotropic cytokine involved in cell proliferation, differentiation and death, and inflammation through binding to specific receptors on cell membranes. Aberrant secretion of TNF-alpha contributes to a number of human diseases, including tumor development and inflammation. TNF-alpha is also an important negative regulator of hematopoiesis. Over-expression of TNF-alpha not only directly inhibits the proliferation and differentiation of hematopoietic cells, but also initiates the intracellular death pathway to induce hematopoietic cell death, leading to bone marrow hematopoiesis failure. In this review, we summarize the mechanisms underlying extrinsic apoptosis and necroptosis of hematopoietic cells induced by TNF-alpha, and discuss the role of TNF-alpha-induced programmed cell death in the pathogenesis of acquired AA. PMID- 26149914 TI - Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed Dose Combination of Cardiovascular Drugs. AB - Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 +/- 18.1 MUg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 +/- 101.3 MUg of lisinopril and 3924 +/- 1011 MUg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds. PMID- 26149915 TI - Anemia in Intensive Cardiac Care Unit patients - An underestimated problem. AB - The heterogeneous group of patients admitted to Intensive Cardiac Care Unit (ICCU) as well as nonspecific complaints associated with anemia might be the reason for underdiagnosing or minimization of this problem. Because of this heterogeneity, there are no clear guidelines to follow. It is known that anemia is impairing the outcome. Thus, it is crucial to keep alert in the diagnosis and treatment of anemia, especially in critically ill cardiac patients. The greatest groups of patients admitted to ICCU are those with acute coronary syndromes (ACS), acute decompensated heart failure (ADHF), severe arrhythmias as well as individuals after cardiac operations. However, patients suffering other critical cardiac illnesses quite often become anemic during hospitalization in ICCU. It is because anemia is typed in the clinical features of heavy diseases or may be the consequence of treatment. The current review focuses on the incidence, complex etiology and predictive role of anemia in a diverse group of ICCU patients. It discusses clinical aspects of anemia treatment in particular groups of critically ill cardiac patients because proper treatment increases chances for recovery and improves the outcome in this severe group of patients. PMID- 26149916 TI - An evaluation model of surgery capability of tertiary hospital in disasters: a cross-sectional survey in China. PMID- 26149917 TI - [A new auto-inflammatory genetic disease associated with cold urticaria: Plaid involving PLCG2 mutation]. PMID- 26149918 TI - Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer's disease brains. AB - We previously identified the cell adhesion molecule (CAM) pathway as a consistent signal in 2 Alzheimer's disease (AD) genome-wide association studies (GWAS). However, the genetic mechanisms of the CAM pathway in AD are unclear. Here, we conducted pathway analysis using (1) Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways; (2) 4 brain expression GWAS datasets; and (3) 2 whole genome AD case-control expression datasets. Using the 4 brain expression GWAS datasets, we identified that genes regulated by cis-regulatory single-nucleotide polymorphisms (SNPs) were significantly enriched in the CAM pathway (p = 2.05E 06, p = 6.10E-07, p = 2.05E-06, and p = 1.47E-07 for each dataset). Interestingly, CAM is a significantly enriched pathway using down-regulated genes (raw p = 0.0235 and adjusted p = 0.0305) and all differentially expressed genes (raw p = 0.0105 and adjusted p = 0.0156) in dataset 5, and all differentially expressed genes (raw p = 0.0041 and adjusted p = 0.0062) in dataset 6. Collectively, our results show that CAM pathway genes are regulated by cis regulatory SNPs and show significantly altered expression in AD. We believe that our results advance the understanding of AD mechanisms and will be useful for future genetic studies of AD. PMID- 26149919 TI - Mitochondrial decline precedes phenotype development in the complement factor H mouse model of retinal degeneration but can be corrected by near infrared light. AB - Mitochondria produce adenosine triphosphate (ATP), critical for cellular metabolism. ATP declines with age, which is associated with inflammation. Here, we measure retinal and brain ATP in normal C57BL/6 and complement factor H knockout mice (Cfh(-/-)), which are proposed as a model of age-related macular degeneration. We show a significant premature 30% decline in retinal ATP in Cfh( /-) mice and a subsequent shift in expression of a heat shock protein that is predominantly mitochondrial (Hsp60). Changes in Hsp60 are associated with stress and neuroprotection. We find no differences in brain ATP between C57BL/6 and Cfh( /-) mice. Near infrared (NIR) increases ATP and reduces inflammation. ATP decline in Cfh(-/-) mice was corrected with NIR which also shifted Hsp60 labeling patterns. ATP decline in Cfh(-/-) mice occurs before inflammation becomes established and photoreceptor loss occurs and may relate to disease etiology. However, ATP levels were corrected with NIR. In summary, we provide evidence for a mitochondrial basis for this disease in mice and correct this with simple light exposure known to improve mitochondrial function. PMID- 26149920 TI - Mutational analysis of SYNJ1 gene (PARK20) in Parkinson's disease in a Taiwanese population. AB - Whole-exome sequencing recently identified a homozygous truncating mutation in Synaptojanin 1 (SYNJ1, PARK20), p.Arg258Gln, in 2 independent families with autosomal recessive young-onset parkinsonism with seizures and cognitive decline. This mutation's role in typical Parkinson's disease (PD) is unclear. We sequenced all coding exons and exon-intron boundaries of SYNJ1 gene in a total of 700 participants: 250 early-onset PD patients, 100 familial PD patients with family history, and 350 age/sex-matched controls from Taiwan. No patients harbored homozygous or compound heterozygous mutations of SYNJ1 gene in our study population. We observed 1 novel missense substitution, p.Ala551Val, in a single heterozygous state in 1 early-onset PD patient. This variant was not observed in controls with total 700 normal alleles. The clinical phenotype of this genetic variant carrier is similar to that seen in idiopathic PD, with motor fluctuation after 11 years of PD diagnosis and comorbidity with dementia after 13 years of motor symptoms. Our results suggest that mutations in SYNJ1 gene do not play a major role in early-onset or familial PD in our population. PMID- 26149921 TI - Increased oligomerization and phosphorylation of alpha-synuclein are associated with decreased activity of glucocerebrosidase and protein phosphatase 2A in aging monkey brains. AB - Aging is associated with an increased risk for Parkinson's disease and dementia with Lewy bodies, in which alpha-synuclein (alpha-syn) oligomerization plays key pathogenic roles. Here, we show that oligomeric alpha-syn levels increase with age in the brain of cynomolgus monkeys and are accompanied by a decrease in the expression and activity of glucocerebrosidase (GCase), a lysosomal enzyme whose dysfunction is linked to accumulation of oligomeric alpha-syn. Besides, levels of alpha-syn phosphorylated at serine 129 (pS129 alpha-syn), a modification that promotes alpha-syn oligomerization also increase with age in the brain and is associated with a reduction in the activity of protein phosphatase 2A (PP2A), an enzyme that facilitates alpha-syn dephosphorylation. The inverse relationship between levels of oligomeric alpha-syn and pS129 alpha-syn and activity of GCase and PP2A was more evident in brain regions susceptible to neurodegeneration (i.e., the striatum and hippocampus) than those that are less vulnerable (i.e., cerebellum and occipital cortex). In vitro experiments showed that GCase activity was more potently inhibited by oligomeric than by monomeric alpha-syn in the lysosome-enriched fractions isolated from brain tissues and cultured neuronal cells. Inhibition of GCase activity induced an elevation of oligomeric alpha-syn levels, which was shown to increase pS129 alpha-syn levels and reduce PP2A activity in cultured neuronal cells. The alterations in oligomeric and pS129 alpha-syns and their association with GCase and PP2A in aging brains may explain the vulnerability of certain brain regions to neurodegeneration in Parkinson's disease and dementia with Lewy bodies. PMID- 26149922 TI - Secondary Metabolites Isolated from the Amazonian Endophytic Fungus Diaporthe sp. SNB-GSS10. AB - We describe a Sabicea cinerea endophytic fungus closely related to Diaporthe pseudomangiferae that produces two known metabolites, mycoepoxydiene (1) and altiloxin A (2), as well as enamidin (3) and eremofortin F (4), two compounds not previously described in the literature. The structure of these four metabolites was elucidated using spectroscopic analysis, and their cytotoxic activities were measured against the human cell lines KB, MRC-5, and MDA-MB-435. PMID- 26149923 TI - Clinical and serological features of patients with dermatomyositis complicated by spontaneous pneumomediastinum. AB - The purpose of this study was to explore the clinical and serological features of patients with pneumomediastinum (PNM) and dermatomyositis-associated interstitial lung disease (DM-ILD). A total of 93 patients (68 with classic DM and 25 with clinically amyopathic DM [CADM]) were recruited. Clinical and laboratory data were collected retrospectively. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies were detected using enzyme-linked immunosorbent assay (ELISA). Variables were compared between patients with and those without PNM. Multivariate analysis was performed using a multivariate logistic regression model. A total of 11 patients developed spontaneous PNM. During the follow-up period, 6 patients died of respiratory failure. No differences in sex, age at the onset of DM, serum ferritin levels, and C-reactive protein (CRP) levels were observed between DM patients with and without PNM. Compared with DM patients without PNM, those with PNM had significantly higher frequencies of rapidly progressive ILD (RP-ILD) (63.6 vs 24.4 %, P = 0.01), anti-MDA5 antibodies (90.9 vs 52.4 %, P = 0.02), CADM diagnoses (63.6 vs 22.0 %, P = 0.007) and cutaneous ulcers (36.4 vs 11 %, P = 0.04), but significantly lower creatine kinase (CK) levels (58.5 vs 284 U/l, P = 0.04). The multivariate analysis indicated that cutaneous ulcer was the only independent risk factor for the occurrence of PNM in DM (OR = 5.98, 95 % confidence interval [CI] 1.12-31.98, P = 0.037). PNM is a refractory complication and tends to occur in DM patients with RP-ILD, anti-MDA5 antibody, CADM diagnosis, and low CK level, and especially in patients with cutaneous ulcers. PMID- 26149924 TI - Role of Lipids in Folding, Misfolding and Function of Integral Membrane Proteins. AB - The lipid bilayer that constitutes cell membranes imposes environmental constraints on the structure, folding and function of integral membrane proteins. The cell membrane is an enormously heterogeneous and dynamic system in its chemical composition and associated physical forces. The lipid compositions of cell membranes not only vary over the tree of life but also differ by subcellular compartments within the same organism. Even in the same subcellular compartment, the membrane composition shows strong temporal and spatial dependence on the environmental or biological cues. Hence, one may expect that the membrane protein conformations and their equilibria strongly depend on the physicochemical variables of the lipid bilayer. Contrary to this expectation, the structures of homologous membrane proteins belonging to the same family but from evolutionary distant organisms exhibit a striking similarity. Furthermore, the atomic structures of the same protein in different lipid environments are also very similar. This suggests that certain stable folds optimized for a specific function have been selected by evolution. On the other hand, there is growing evidence that, despite the overall stability of the protein folds, functions of certain membrane proteins require a particular lipid composition in the bulk bilayer or binding of specific lipid species. Here I discuss the specific and nonspecific modulation of folding, misfolding and function of membrane proteins by lipids and introduce several diseases that are caused by misfolding of membrane proteins. PMID- 26149925 TI - Protein Misfolding in Lipid-Mimetic Environments. AB - Among various cellular factors contributing to protein misfolding and subsequent aggregation, membranes occupy a special position due to the two-way relations between the aggregating proteins and cell membranes. On one hand, the unstable, toxic pre-fibrillar aggregates may interact with cell membranes, impairing their functions, altering ion distribution across the membranes, and possibly forming non-specific membrane pores. On the other hand, membranes, too, can modify structures of many proteins and affect the misfolding and aggregation of amyloidogenic proteins. The effects of membranes on protein structure and aggregation can be described in terms of the "membrane field" that takes into account both the negative electrostatic potential of the membrane surface and the local decrease in the dielectric constant. Water-alcohol (or other organic solvent) mixtures at moderately low pH are used as model systems to study the joint action of the local decrease of pH and dielectric constant near the membrane surface on the structure and aggregation of proteins. This chapter describes general mechanisms of structural changes of proteins in such model environments and provides examples of various proteins aggregating in the "membrane field" or in lipid-mimetic environments. PMID- 26149926 TI - Lipids in Amyloid-beta Processing, Aggregation, and Toxicity. AB - Aggregation of amyloid-beta (Abeta) peptide is the major event underlying neuronal damage in Alzheimer's disease (AD). Specific lipids and their homeostasis play important roles in this and other neurodegenerative disorders. The complex interplay between the lipids and the generation, clearance or deposition of Abeta has been intensively investigated and is reviewed in this chapter. Membrane lipids can have an important influence on the biogenesis of Abeta from its precursor protein. In particular, increased cholesterol in the plasma membrane augments Abeta generation and shows a strong positive correlation with AD progression. Furthermore, apolipoprotein E, which transports cholesterol in the cerebrospinal fluid and is known to interact with Abeta or compete with it for the lipoprotein receptor binding, significantly influences Abeta clearance in an isoform-specific manner and is the major genetic risk factor for AD. Abeta is an amphiphilic peptide that interacts with various lipids, proteins and their assemblies, which can lead to variation in Abeta aggregation in vitro and in vivo. Upon interaction with the lipid raft components, such as cholesterol, gangliosides and phospholipids, Abeta can aggregate on the cell membrane and thereby disrupt it, perhaps by forming channel-like pores. This leads to perturbed cellular calcium homeostasis, suggesting that Abeta-lipid interactions at the cell membrane probably trigger the neurotoxic cascade in AD. Here, we overview the roles of specific lipids, lipid assemblies and apolipoprotein E in Abeta processing, clearance and aggregation, and discuss the contribution of these factors to the neurotoxicity in AD. PMID- 26149928 TI - Intrinsic Stability, Oligomerization, and Amyloidogenicity of HDL-Free Serum Amyloid A. AB - Serum amyloid A (SAA) is an acute-phase reactant protein predominantly bound to high-density lipoprotein in serum and presumed to play various biological and pathological roles. Upon tissue trauma or infection, hepatic expression of SAA increases up to 1,000 times the basal levels. Prolonged increased levels of SAA may lead to amyloid A (AA) amyloidosis, a usually fatal systemic disease in which the amyloid deposits are mostly comprised of the N-terminal 1-76 fragment of SAA. SAA isoforms may differ across species in their ability to cause AA amyloidosis, and the mechanism of pathogenicity remains poorly understood. In vitro studies have shown that SAA is a marginally stable protein that folds into various oligomeric species at 4 degrees C. However, SAA is largely disordered at 37 degrees C, reminiscent of intrinsically disordered proteins. Non-pathogenic murine (m)SAA2.2 spontaneously forms amyloid fibrils in vitro at 37 degrees C whereas pathogenic mSAA1.1 has a long lag (nucleation) phase, and eventually forms fibrils of different morphology than mSAA2.2. Remarkably, human SAA1.1 does not form mature fibrils in vitro. Thus, it appears that the intrinsic amyloidogenicity of SAA is not a key determinant of pathogenicity, and that other factors, including fibrillation kinetics, ligand binding effects, fibril stability, nucleation efficiency, and SAA degradation may play key roles. This chapter will focus on the known structural and biophysical properties of SAA and discuss how these properties may help better understand the molecular mechanism of AA amyloidosis. PMID- 26149929 TI - Interactions of Lipid Membranes with Fibrillar Protein Aggregates. AB - Amyloid fibrils are an intriguing class of protein aggregates with distinct physicochemical, structural and morphological properties. They display peculiar membrane-binding behavior, thus adding complexity to the problem of protein-lipid interactions. The consensus that emerged during the past decade is that amyloid cytotoxicity arises from a continuum of cross-beta-sheet assemblies including mature fibrils. Based on literature survey and our own data, in this chapter we address several aspects of fibril-lipid interactions, including (i) the effects of amyloid assemblies on molecular organization of lipid bilayer; (ii) competition between fibrillar and monomeric membrane-associating proteins for binding to the lipid surface; and (iii) the effects of lipids on the structural morphology of fibrillar aggregates. To illustrate some of the processes occurring in fibril-lipid systems, we present and analyze fluorescence data reporting on lipid bilayer interactions with fibrillar lysozyme and with the N-terminal 83 residue fragment of amyloidogenic mutant apolipoprotein A-I, 1-83/G26R/W@8. The results help understand possible mechanisms of interaction and mutual remodeling of amyloid fibers and lipid membranes, which may contribute to amyloid cytotoxicity. PMID- 26149927 TI - Role of Cholesterol and Phospholipids in Amylin Misfolding, Aggregation and Etiology of Islet Amyloidosis. AB - Amyloidosis is a biological event in which proteins undergo structural transitions from soluble monomers and oligomers to insoluble fibrillar aggregates that are often toxic to cells. Exactly how amyloid proteins, such as the pancreatic hormone amylin, aggregate and kill cells is still unclear. Islet amyloid polypeptide, or amylin, is a recently discovered hormone that is stored and co-released with insulin from pancreatic islet beta-cells. The pathology of type 2 diabetes mellitus (T2DM) is characterized by an excessive extracellular and intracellular accumulation of toxic amylin species, soluble oligomers and insoluble fibrils, in islets, eventually leading to beta-cell loss. Obesity and elevated serum cholesterol levels are additional risk factors implicated in the development of T2DM. Because the homeostatic balance between cholesterol synthesis and uptake is lost in diabetics, and amylin aggregation is a hallmark of T2DM, this chapter focuses on the biophysical and cell biology studies exploring molecular mechanisms by which cholesterol and phospholipids modulate secondary structure, folding and aggregation of human amylin and other amyloid proteins on membranes and in cells. Amylin turnover and toxicity in pancreatic cells and the regulatory role of cholesterol in these processes are also discussed. PMID- 26149930 TI - The Role of Lipid in Misfolding and Amyloid Fibril Formation by Apolipoprotein C II. AB - Apolipoproteins are a key component of lipid transport in the circulatory system and share a number of structural features that facilitate this role. When bound to lipoprotein particles, these proteins are relatively stable. However, in the absence of lipids they display conformational instability and a propensity to aggregate into amyloid fibrils. Apolipoprotein C-II (apoC-II) is a member of the apolipoprotein family that has been well characterised in terms of its misfolding and aggregation. In the absence of lipid, and at physiological ionic strength and pH, apoC-II readily forms amyloid fibrils with a twisted ribbon-like morphology that are amenable to a range of biophysical and structural analyses. Consistent with its lipid binding function, the misfolding and aggregation of apoC-II are substantially affected by the presence of lipid. Short-chain phospholipids at submicellar concentrations significantly accelerate amyloid formation by inducing a tetrameric form of apoC-II that can nucleate fibril aggregation. Conversely, phospholipid micelles and bilayers inhibit the formation of apoC-II ribbon-type fibrils, but induce slow formation of amyloid with a distinct straight fibril morphology. Our studies of the effects of lipid at each stage of amyloid formation, detailed in this chapter, have revealed complex behaviour dependent on the chemical nature of the lipid molecule, its association state, and the protein:lipid ratio. PMID- 26149932 TI - Computational Approaches to Identification of Aggregation Sites and the Mechanism of Amyloid Growth. AB - This chapter describes computational approaches to study amyloid formation. The first part addresses identification of potential amyloidogenic regions in the amino acid sequences of proteins and peptides. Next, we discuss nucleation and aggregation sites in protein folding and misfolding. The last part describes up to-date kinetic models of amyloid fibrils formation. Numerous studies show that protein misfolding is initiated by specific amino acid segments with high amyloid forming propensity. The ability to identify and, ultimately, block such segments is very important. To this end, many prediction algorithms have been developed which vary greatly in their effectiveness. We compared the predictions for 30 proteins by using different methods and found that, at best, only 50% of residues in amyloidogenic segments were predicted correctly. The best results were obtained by using the meta-servers that combine several independent approaches, and by the method PASTA2. Thus, correct prediction of amyloidogenic segments remains a difficult task. Additional data and new algorithms that are becoming available are expected to improve the accuracy of the prediction methods, particularly if they use 3D structural information on the target proteins. At the same time, our understanding of the kinetics of fibril formation is more advanced. The current kinetic models outlined in this chapter adequately describe the key features of amyloid nucleation and growth. However, the underlying structural details are less clear, not least because of the apparently different mechanisms of amyloid fibril formation which are discussed. Ultimately, the detailed understanding of the structural basis for amyloidogenesis should help develop rational therapies to block this pathogenic process. PMID- 26149933 TI - Role of Syndecans in Lipid Metabolism and Human Diseases. AB - Syndecans are transmembrane heparan sulfate proteoglycans involved in the regulation of cell growth, differentiation, adhesion, neuronal development, and lipid metabolism. Syndecans are expressed in a tissue-specific manner to facilitate diverse cellular processes. As receptors and co-receptors, syndecans provide promising therapeutic targets that bind to a variety of physiologically important ligands. Negatively charged glycosaminoglycan chains of syndecans, located in the extracellular compartment, are critical for such binding. Functions of syndecans are as diverse as their ligands. For example, hepatic syndecan-1 mediates clearance of triglyceride-rich lipoproteins. Syndecan-2 promotes localization of Alzheimer's amyloid Abeta peptide to the cell surface, which is proposed to contribute to amyloid plaque formation. Syndecan-3 helps co localize the appetite-regulating melanocortin-4 receptor with its agonist, leading to an increased appetite. Finally, syndecan-4 initiates the capture of modified low-density lipoproteins by macrophages and thereby promotes the atheroma formation. We hypothesize that syndecan modifications such as desulfation of glycosaminoglycan chains may contribute to a wide range of diseases, from atherosclerosis to type 2 diabetes. At the same time, desulfated syndecans may have beneficial effects, as they can inhibit amyloid plaque formation or decrease the appetite. Despite considerable progress in understanding diverse functions of syndecans, the complex physiological roles of this intriguing family of proteoglycans are far from clear. Additional studies of syndecans may potentially help develop novel therapeutic approaches and diagnostic tools to alleviate complex human diseases such as cardiovascular and Alzheimer's diseases. PMID- 26149934 TI - HPLC-UV method development and validation for the quantification of ropinirole in new PLGA multiparticulate systems: Microspheres and nanoparticles. AB - A simple HPLC-UV method was developed and validated for the quantitation of RP free base encapsulated into two new multiparticulate systems (microparticles and nanoparticles), as well as for the quantification of RP hydrochloride when given as a loading dose together with the new delivery system developed. HPLC separation was achieved using a C18 Kromasil column (250 mm * 4 mm) with a mobile phase composed of acetonitrile-phosphate buffer solution (55:45, v/v) adjusted at pH 6.0 and containing 0.3% triethanolamine. Flow rate was set at 1.0 mL min(-1). The UV detector was operated at 245 nm. The method allowed for the simultaneous determination of both RP and RP-HCl. The method was linear within the range 2.5 50 MUg mL(-1) for both RP and RP-HCl. The limits of detection (LOD) and quantitation (LOQ) found were 0.8 MUg mL(-1) and 2.4 MUg mL(-1) for RP, and 0.3 MUg mL(-1) and 0.9 MUg mL(-1) for RP-HCl. The method was found to be simple, rapid, specific, precise, accurate, and reproducible. The method was successfully applied to the determination of the encapsulation efficiency of RP in the multiparticulate systems developed, being 85.03 +/- 3.77% and 51.12 +/- 3.50%, for RP-loaded PLGA microspheres and RP-loaded PLGA nanoparticles, respectively. PMID- 26149935 TI - Development of DH-I-180-3 loaded lipid nanoparticle for photodynamic therapy. AB - Photodynamic therapy (PDT) is a promising noninvasive treatment modality for cancer. Photosensitizer and specific wave length of light are the key component of PDT. DH-I-180-3, a second generation photosensitizer, was incorporated into lipid nanoparticle for simultaneous fluorescent imaging and targeting therapy. Solid lipid nanoparticle (SLN) and nanostructured lipid carriers (NLC) based on poloxamer 188 as surfactant and lecithin as co-surfactant were prepared using solvent evaporation and hot homogenization technique. Stearic acid and Capmul((r)) MCM C8 were utilized as solid lipid and liquid lipid, respectively. The particle size of SLN and NLCs was around 200 nm and decreased when a part of stearic acid was replaced with Capmul((r)) MCM C8. Drug loading efficacy was significantly enhanced when the percentage amount of liquid lipid increased. All the polydispersity indices of the SLN/NLCs were below 0.3, and displayed a narrow particle size distribution. Zeta potentials of all the lipid nanoparticles were below -30 mV, maintaining sufficient repulsive force and achieving enhanced physical stability. No significant change in the particle size and polydispersity index was observed from lyophilized SLN/NLCs. When the photocytotoxic effects of the formulations were evaluated in MCF-7 cells, GI 50 of SLN was less than half of DH-I-180-3 solution, and NLCs containing either 5 or 15%w/w of Capmul((r)) MCM C8 exerted higher cytotoxicity than SLN. The fluorescence microscope images displayed enhanced cellular accumulation of DH-I-180-3 loaded in SLN and NLCs, which was closely correlated with the photocytotoxicity results. It was concluded that the incorporation of DH-I-180-3 into the nanoparticles enhanced their targeting efficacy and improved photocytotoxicity. PMID- 26149931 TI - Amyloid-Forming Properties of Human Apolipoproteins: Sequence Analyses and Structural Insights. AB - Apolipoproteins are protein constituents of lipoproteins that transport cholesterol and fat in circulation and are central to cardiovascular health and disease. Soluble apolipoproteins can transiently dissociate from the lipoprotein surface in a labile free form that can misfold, potentially leading to amyloid disease. Misfolding of apoA-I, apoA-II, and serum amyloid A (SAA) causes systemic amyloidoses, apoE4 is a critical risk factor in Alzheimer's disease, and apolipoprotein misfolding is also implicated in cardiovascular disease. To explain why apolipoproteins are over-represented in amyloidoses, it was proposed that the amphipathic alpha-helices, which form the lipid surface-binding motif in this protein family, have high amyloid-forming propensity. Here, we use 12 sequence-based bioinformatics approaches to assess amyloid-forming potential of human apolipoproteins and to identify segments that are likely to initiate beta aggregation. Mapping such segments on the available atomic structures of apolipoproteins helps explain why some of them readily form amyloid while others do not. Our analysis shows that nearly all amyloidogenic segments: (i) are largely hydrophobic, (ii) are located in the lipid-binding amphipathic alpha helices in the native structures of soluble apolipoproteins, (iii) are predicted in both native alpha-helices and beta-sheets in the insoluble apoB, and (iv) are predicted to form parallel in-register beta-sheet in amyloid. Most of these predictions have been verified experimentally for apoC-II, apoA-I, apoA-II and SAA. Surprisingly, the rank order of the amino acid sequence propensity to form amyloid (apoB>apoA-II>apoC-II>=apoA-I, apoC-III, SAA, apoC-I>apoA-IV, apoA-V, apoE) does not correlate with the proteins' involvement in amyloidosis. Rather, it correlates directly with the strength of the protein-lipid association, which increases with increasing protein hydrophobicity. Therefore, the lipid surface binding function and the amyloid-forming propensity are both rooted in apolipoproteins' hydrophobicity, suggesting that functional constraints make it difficult to completely eliminate pathogenic apolipoprotein misfolding. We propose that apolipoproteins have evolved protective mechanisms against misfolding, such as the sequestration of the amyloidogenic segments via the native protein-lipid and protein-protein interactions involving amphipathic alpha helices and, in case of apoB, beta-sheets. PMID- 26149936 TI - The potential of adjuvants to improve immune responses against TdaP vaccines: A preclinical evaluation of MF59 and monophosphoryl lipid A. AB - The successful approach of combining diphtheria, tetanus and pertussis antigens into a single vaccine has become a cornerstone of immunization programs. Yet, even if vaccination coverage is high, a resurgence of pertussis has been reported in many countries suggesting current vaccines may not provide adequate protection. To induce better tailored and more durable immune responses against pertussis vaccines different approaches have been proposed, including the use of novel adjuvants. Licensed aP vaccines contain aluminum salts, which mainly stimulate humoral immune responses and might not be ideal for protecting against Bordetella pertussis infection. Adjuvants inducing more balanced T-helper profiles or even Th1-prone responses might be more adequate. In this study, two adjuvants already approved for human use have been tested: MF59 emulsion and the combination of aluminum hydroxide with the Toll-Like Receptor 4 agonist MPLA. Adjuvanticity was evaluated in a mouse model using a TdaP vaccine containing three B. pertussis antigens: genetically detoxified pertussis toxin (PT-9K/129G), filamentous hemagglutinin (FHA) and pertactin (PRN) The physico-chemical compatibility of TdaP antigens with the proposed adjuvants, together with a quicker onset and changed quality of the antibody responses, fully supports the replacement of aluminum salts with a new adjuvant to enhance aP vaccines immunogenicity. PMID- 26149937 TI - Simultaneous ureteroscopic lithotripsy and contralateral percutaneous nephrolithotomy for ureteral calculi combined with renal staghorn calculi. AB - OBJECTIVES: To investigate the efficacy, safety, and cost-effectiveness of simultaneous ureteroscopic lithotripsy and contralateral percutaneous nephrolithotomy for ureteral calculi combined with contralateral renal staghorn calculi. METHODS: The present prospective controlled trial had been registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR-ONRC 13004146). Patients with ureteral calculi and contralateral renal staghorn calculi were enrolled into the staged (ureteroscopic lithotripsy first followed by a staged percutaneous nephrolithotomy) or the simultaneous (synchronous ureteroscopic lithotripsy and contralateral percutaneous nephrolithotomy) treatment group according to the odd or even number of the last hospitalization number. All patients signed informed consent. The primary outcomes were the stone free rate and total hospital costs. The second outcomes were the operative and anesthesia times, the complication rate, and hospital stay. RESULTS: A total of 51 patients were enrolled into the staged group and 52 patients were enrolled into the simultaneous group. There were no statistically significant differences in patients' characteristics. The overall stone-free rate was 94.1% in the staged group and 92.3% in the simultaneous group. No severe complication was observed. The total hospital stay of the staged group was longer, and it was negatively correlated to different procedures. The cost in the staged group was higher, and it was correlated with total operation time and postoperative hospital stay. CONCLUSIONS: Simultaneous ureteroscopic lithotripsy and contralateral percutaneous nephrolithotomy represent safe and effective procedures, and they can be considered as a first-line treatment for selected patients presenting with ureteral calculi combined with contralateral renal calculi. PMID- 26149938 TI - Salvage of a free osteocutaneous fibula flap by creating a distal arteriovenous fistula in facial reconstruction. AB - The case of a 25-year-old male with a facial gunshot wound is reported. A free fibula flap was performed for facial reconstruction. At 48 h after the operation, a thrombotic event was observed in the anastomosis. A distal arteriovenous (AV) fistula was performed to regulate the blood flow in the flap, and a combination of flaps (forehead flap and internal mammary artery perforator (IMAP) flap) was used for the skin defects. After creating the distal AV fistula, the blood flow was regulated and the free flap salvaged. No bone healing problem was observed in the free fibula flap and there were no complications related to the forehead and IMAP flaps. The fistula was patent at 2 years postoperative. Although all high resistance flap conditions cannot be corrected with a distal AV fistula, the method presented in this case could be used as a last resort procedure for free flap salvage. PMID- 26149939 TI - The role of XRCC6/Ku70 in nasopharyngeal carcinoma. AB - The association between XRCC6/Ku70, an upstream player in the DNA double-strand break repair system, and the risk of nasopharyngeal carcinoma (NPC) was examined. In this case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of XRCC6 promoter T-991C (rs5751129), promoter G 57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with NPC risk were evaluated. NPC tissue samples were also assessed for their XRCC6 mRNA and protein expression by real-time quantitative reverse transcription PCR and Western blotting, respectively. With regard to the XRCC6 promoter T-991C, the TC and CC genotypes were associated with a significantly increased risk of NPC compared with wild-type TT genotype (adjusted odds ratio 2.02 and 3.42, 95% confidence interval 1.21-3.32 and 1.28-8.94, P=0.0072 and 0.0165, respectively). The mRNA and protein expression levels for NPC tissues revealed significantly lower XRCC6 mRNA and protein expression in the NPC samples with TC/CC genotypes compared to those with the TT genotype (P=0.0210 and 0.0164, respectively). These findings suggest that XRCC6 may play an important role in the carcinogenesis of NPC and could serve as a chemotherapeutic target for personalized medicine and therapy. PMID- 26149940 TI - Topical combined application of dexamethasone, vitamin C, and beta-sodium glycerophosphate for healing the extraction socket in rabbits. AB - An osteogenic inducer (OI) consisting of dexamethasone, vitamin C, and beta sodium glycerophosphate has the capacity to induce bone formation in vitro. The aim of this study was to assess the efficacy of the application of this OI on extraction socket healing. The bilateral first mandibular premolars were extracted from 75 New Zealand rabbits. Gelatin sponges carrying OI were implanted into the sockets. Sockets undergoing implantation of gelatin sponges alone were also evaluated, as well as non-implantation sockets. Specimens from each group were evaluated radiographically, histologically, and histomorphometrically using haematoxylin-eosin staining. Results showed earlier new bone formation and higher bone quality and quantity in the OI group compared to the other groups, and the differences were significant at 2, 4, 8, and 12 weeks postoperative. The OI significantly reduced the absorption of alveolar bone in terms of height; however, changes in the width were not significantly different between the three groups (P>0.05). The OI was shown to have a positive effect on healing of the tooth extraction sockets, was inexpensive, and was convenient to use during the operational procedure; therefore this could represent a promising implant material for human clinical application. PMID- 26149941 TI - Sexual and urinary functions after robot-assisted versus pure laparoscopic total mesorectal excision for rectal cancer. PMID- 26149942 TI - Complications from the primary tumour are not related with survival in patients with synchronous stage IV colorectal cancer receiving chemotherapy without primary tumour resection. AB - BACKGROUND: The aim of this study was to evaluate the rate of complications from the primary tumour (CPT) requiring surgical or endoscopic intervention during chemotherapy treatment in patients with incurable synchronous stage IV colorectal cancer, the possibility of predicting such complications and their influence on survival. METHODS: One hundred and twenty-five patients were initially treated with chemotherapy. Patients were grouped on the basis of appearance or not of CPT. We assessed the relation between age, gender, carcinoembryonic antigen (CEA) level, primary tumour location, alkaline phosphatase level, unilobar or bilobar liver involvement, presence of peritoneal carcinomatosis, the number of sites of metastatic disease, the addition of target therapies to chemotherapy, the ability to traverse the tumour with an endoscope and the appearance of complications due to the primary tumour and overall survival. RESULTS: Mean age was 64.9 years, and 89 patients were men. Over a mean of 234 days, 25 patients (20 %) developed a CPT. Eighteen patients required surgery, and seven were treated exclusively by an endoscopic procedure. Mean survival was 15.8 months. We found a statistically relevant correlation between the inability to traverse the tumour with an endoscope and the occurrence of a CPT. There was no statistical differences in survival between both groups, but patients receiving target therapies had better survival. CONCLUSION: Twenty percent of patients will suffer a CPT during chemotherapy treatment. The inability to pass the tumour with an endoscope can predict the CPT. Survival was only related to the addition of target therapies to chemotherapy. PMID- 26149943 TI - Rectal stump suspension: a novel technique to facilitate and shorten totally laparoscopic Hartmann reversal. PMID- 26149944 TI - Infliximab-induced thrombocytopenia in a patient with ulcerative colitis. PMID- 26149945 TI - The role of heparin in a warfarinized patient with mesenteric venous thrombosis. PMID- 26149946 TI - Protein covalent immobilization via its scarce thiol versus abundant amine groups: Effect on orientation, cell binding domain exposure and conformational lability. AB - Quantity, orientation, conformation and covalent linkage of naturally cell adhesive proteins adsorbed or covalently linked to a surface, are known to influence the preservation of their subsequent long term cell adhesion properties and bioactivity. In the present work, we explore two different strategies for the covalent linking of plasma fibronectin (pFN) - used as a cell adhesive model protein, onto a polystyrene (PS) surface. One is aimed at tethering the protein to the surface in a semi-oriented fashion (via one of the 4 free thiol reactive groups on the protein) with a heterofunctional coupling agent (SSMPB method). The other aims to immobilize the protein in a more random fashion by reaction between the abundant pendant primary amine bearing amino acids of the pFN and activated carboxylic surface functions obtained after glutaric anhydride surface treatment (GA method). The overall goal will be to verify the hypothesis of a correlation between covalent immobilization of a model cell adhesive protein to a PS surface in a semi-oriented configuration (versus randomly oriented) with promotion of enhanced exposure of the protein's cell binding domain. This in turn would lead to enhanced cell adhesion. Ideally the goal is to elaborate substrates exhibiting a long term stable protein monolayer with preserved cell adhesive properties and bioactivity for biomaterial and/or cell adhesion commercial plate applications. However, the initial restrictive objective of this paper is to first quantitatively and qualitatively investigate the reversibly (merely adsorbed) versus covalently irreversibly bound protein to the surface after the immobilization procedure. Although immobilized surface amounts were similar (close to the monolayer range) for all immobilization approaches, covalent grafting showed improved retention and stronger "tethering" of the pFN protein to the surface (roughly 40%) after SDS rinsing compared to that for mere adsorption (0%) suggesting an added value to the covalent grafting immobilization methods. However no differences in exposure of the cell binding domains were observed (ELISA results) before SDS rinsing, suggesting that pFN protein grafting to the surface is initially kinetically driven be a stochastic random adsorption phenomenon. Covalent grafting acts in the final stage as a process that simply tethers and stabilizes (or freezes) the initial conformation/orientation of the adsorbed protein on the surface. In addition covalent linkage via the SSMPB approach is likely favored by surface-induce exposure of one of the normally hidden free thiol group pair, thus optimizing covalent linkage to the surface. However after SDS rinsing, this "tethering"/"freezing" effect was significantly more prominent for the GA grafting approach (due to greater number of potential covalent links between the protein and the surface) compared to that for the SSMPB approach. This hypothesis was buttressed by the improved resistance to denaturation (smaller conformational lability) for the GA compared to the SMPB approach and improved exposure of the cell binding domain for the former (>50%) even after SDS rinsing. These results are promising in that they suggest covalent tethering of fibronectin to PS substrate in a monolayer range, with significantly improved irreversible protein surface bonding via both approaches (compared to that for mere adsorption). The latter are likely applicable to a wide range of proteins. PMID- 26149947 TI - Hyaluronic acid and polyethylenimine self-assembled polyion complexes as pH sensitive drug carrier for cancer therapy. AB - In this study, a series of polyion complexes (PICs) were prepared via electrostatic interaction between hyaluronic acid-histidine conjugate (HH) and polyethylenimine-histidine conjugate (PH). These PICs with the average size ranging from 410.5 nm to 98.5 nm at different weight ratios of HH/PH were able to encapsulate doxorubicin (DOX) as the model antitumor drug. The PICs at the weight ratio of 4:1 had negative surface charge and were of good dispersity and stability in the solution containing serum. In vitro drug release assay demonstrated that the DOX release rate were higher at acidic pH showing a controllable property. These HA coated PICs could targetedly deliver DOX to B16F10 tumor cells, showing improved antitumor activity. PMID- 26149948 TI - Rectal puncture complicating caudal blockade in a child with severe rectal distension. AB - We describe a case of unrecognized rectal puncture following unsuccessful caudal blockade in a patient later found to have marked rectal distension on MRI. This may have contributed to the rectal injury. PMID- 26149950 TI - Evaluating Hair as a Predictor of Blood Mercury: The Influence of Ontogenetic Phase and Life History in Pinnipeds. AB - Mercury (Hg) biomonitoring of pinnipeds increasingly utilizes nonlethally collected tissues such as hair and blood. The relationship between total Hg concentrations ([THg]) in these tissues is not well understood for marine mammals, but it can be important for interpretation of tissue concentrations with respect to ecotoxicology and biomonitoring. We examined [THg] in blood and hair in multiple age classes of four pinniped species. For each species, we used paired blood and hair samples to quantify the ability of [THg] in hair to predict [THg] in blood at the time of sampling and examined the influence of varying ontogenetic phases and life history of the sampled animals. Overall, we found that the relationship between [THg] in hair and blood was affected by factors including age class, weaning status, growth, and the time difference between hair growth and sample collection. Hair [THg] was moderately to strongly predictive of current blood [THg] for adult female Steller sea lions (Eumetopias jubatus), adult female California sea lions (Zalophus californianus), and adult harbor seals (Phoca vitulina), whereas hair [THg] was poorly predictive or not predictive (different times of year) of blood [THg] for adult northern elephant seals (Mirounga angustirostris). Within species, except for very young pups, hair [THg] was a weaker predictor of blood [THg] for prereproductive animals than for adults likely due to growth, variability in foraging behavior, and transitions between ontogenetic phases. Our results indicate that the relationship between hair [THg] and blood [THg] in pinnipeds is variable and that ontogenetic phase and life history should be considered when interpreting [THg] in these tissues. PMID- 26149949 TI - Youth Withdrawal Moderates the Relationhips Between Neighborhood Factors and Internalizing Symptoms in Adolescence. AB - Adolescents higher in temperamental withdrawal are at risk for anxiety and depressive symptoms; however, not all youth higher in withdrawal exhibit internalizing symptoms, suggesting that contextual factors may influence these relationships. We examined whether youth withdrawal moderates the relationships between neighborhood processes (crime, social cohesion) and internalizing symptoms and whether findings were consistent with the diathesis-stress or differential susceptibility hypotheses. Participants were 775 adolescents (M = 15.50 +/- 0.56 years, 72 % male, 76 % White). Adolescents higher in withdrawal manifested higher internalizing symptoms in the context of lower neighborhood crime and lower neighborhood social cohesion than youth lower in withdrawal, supporting diathesis-stress. These findings elucidate neighborhood processes associated with internalizing symptoms, which can inform models of risk and resilience for these symptoms among children who differ in temperamental withdrawal. PMID- 26149951 TI - Simultaneous column preconcentration of ultra trace amounts of heavy metals with nano-adsorbent in some environmental and biological samples. AB - In the present investigation, multi-walled carbon nanotubes impregnated by 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane were prepared and applied as adsorbent for the simultaneous separation of Bi(III), Cu(II), Cd(II) and Pb(II) ions prior to their determination by electrothermal atomic absorption spectrometry. The following analytical figures of merit were determined for bismuth, copper, cadmium and lead, respectively: enrichment factors of 168, 134, 111 and 146, assay precisions of +/-4.6%, +/-4.8%, +/-5.3% and +/-5.0% and detection limits of 11.3, 3.7, 0.5 and 0.3 ng L(-1). The method was successfully applied for the determination of heavy metals in environmental, biological and certified reference materials. PMID- 26149952 TI - Dielectric Optical-Controllable Magnifying Lens by Nonlinear Negative Refraction. AB - A simple optical lens plays an important role for exploring the microscopic world in science and technology by refracting light with tailored spatially varying refractive indices. Recent advancements in nanotechnology enable novel lenses, such as, superlens and hyperlens, with sub-wavelength resolution capabilities by specially designed materials' refractive indices with meta-materials and transformation optics. However, these artificially nano- or micro-engineered lenses usually suffer high losses from metals and are highly demanding in fabrication. Here, we experimentally demonstrate, for the first time, a nonlinear dielectric magnifying lens using negative refraction by degenerate four-wave mixing in a plano-concave glass slide, obtaining magnified images. Moreover, we transform a nonlinear flat lens into a magnifying lens by introducing transformation optics into the nonlinear regime, achieving an all-optical controllable lensing effect through nonlinear wave mixing, which may have many potential applications in microscopy and imaging science. PMID- 26149953 TI - Pneumocystis pneumonia in HIV patients: a diagnostic challenge till date. AB - HIV has become a major health problem in India, patients commonly succumb to opportunistic infections (OIs), respiratory infections being an important cause of morbidity and their accurate diagnosis is still a challenge. Our aim was to study the occurrence of Pneumocystis pneumonia (PCP) in HIV/AIDS patients with respiratory complaints attending ART clinic and to compare various diagnostic methodologies. One hundred and twenty five HIV/AIDS patients presenting with respiratory symptoms like cough, fever, breathlessness etc, were enrolled, and induced sputum samples were collected. Samples were homogenized using glass beads and Dithiothretol. Smears were prepared and examined by Immunoflourescent staining (IFAT), Gomori methanamine silver staining (GMSS), Toludine blue O staining (TBO) and Giemsa staining for Pneumocystis jiroveci. Among the 125 patients who presented with respiratory complaints, 34 cases (27.2%) were diagnosed as having PCP. All 34 cases were detected by IFAT followed by GMSS, Giemsa and Toludine blue O staining in decreasing order. The mean CD4 count was 67.27cells/MUl. PCP has become an important health problem in HIV/AIDS patients with low CD4 counts in India. IFAT remains the most sensitive method for the detection of this uncultivable organism. In resource poor settings where an immunoflourecent microscope is not available, diagnosis of PCP still remains problematic. PMID- 26149954 TI - Corrigendum. AB - Xiaorong Lin*, Nadia Chacko, Linqi Wang and Yashwant Pavuluri. Generation of stable mutants and targeted gene deletion strains in Cryptococcus neoformans through electroporation. Medical Mycology 53(3). 2015: 225-234.DOI: 10.1093/mmy/myu083.The authors wish to make the following corrections in this manuscript. [...] PMID- 26149955 TI - Is non-alcoholic fatty liver disease a systemic disease that promotes extrahepatic cancer development? PMID- 26149956 TI - Emergence of KPC-2-producing Escherichia coli isolates in an urban river in Harbin, China. AB - Three KPC-2-producing Escherichia coli (E1, E2, and E3) were recovered from water samples of an urban river in the city of Harbin, China. Antimicrobial susceptibility was determined by broth microdilution. Molecular characterization and genetic relatedness of the isolates were determined by polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and PCR-directed phylotyping. Plasmids were analyzed by conjugation, S1-PFGE, Southern blotting and PCR-based replicon typing (PBRT). The genetic environment of the bla KPC-2 gene was determined using PCR and sequencing. PCR analyses revealed that the E1 isolate carried the bla KPC-2, bla CMY-2, bla TEM-1, bla CTX-M-14, and qnrB2 genes and belonged to sequence type ST410, phylogenetic type A; the E2 isolate was assigned to ST131-B2 and carried the bla KPC-2, bla TEM-1, bla CTX-M-3, bla DHA-1, aac(6')-Ib-cr, and qnrS1 genes; while the E3 isolate was of ST648-D and possessed bla KPC-2, bla TEM-1, bla OXA 1, bla CTX-M-15, armA, and aac(6')-Ib-cr genes. PFGE demonstrated that each of the three KPC-2-producing E. coli isolates exhibited an individual XbaI patterns. The bla KPC-2 gene was located on plasmids of 60-140 kb with IncA/C, IncN, or non typeable replicon types. The genetic environment of bla KPC-2 of the three strains was consistent with the genetic structure of bla KPC-2 on the plasmid pKP048. PMID- 26149957 TI - Phylogenetic diversity on housekeeping and symbiotic genes of rhizobial from Sphaerophysa in China. AB - This study explored the diversity and phylogeny of rhizobia collected from nodules of Sphaerophysa salsula in different geographical regions of Northwest China. The 16S rRNA gene sequences divided the strains into the following distinct groups: Mesorhizobium, Rhizobium and Shinella. The phylogenies of recA and atpD genes showed low correlation with nifH and nodA gene in most species, which indicated that, the gene recombination between species and genera might have been exist. To our knowledge, this is the first study using the multilocus sequencing analysis Sphaerophysa rhizobia in order to understand the relation between genetic diversity and ecology. PMID- 26149958 TI - Evaluating hypertrophic thyroidectomy scar outcomes after treatment with triamcinolone injections and copper bromide laser therapy. AB - BACKGROUND AND OBJECTIVES: Postoperative hypertrophic scar following thyroidectomy can be a major concern due to its disfiguring appearance. Recently, copper bromide laser (CBL) and intralesional triamcinolone injection (TA ILI) have been used to treat hypertrophic thyroidectomy scars. Data regarding the number of treatment sessions needed to reach a certain endpoint and the prognostic factors that affect treatment duration are unknown. The aim of this study was to evaluate the number of treatment sessions required to reduce VSS score by 50%, which was regarded as the treatment endpoint, and to investigate the factors that influence treatment duration when using CBL and TA ILI. MATERIALS AND METHODS: A total of 67 patients were enrolled in this study. Baseline characteristics of the patients including age, sex, body mass index (BMI), distance of the scar from the sternal notch, time of development of the hypertrophic scar, sternocleidomastoid (SCM) muscle prominence, and date of operation were collected on the first visit. They were treated with CBL and TA. The concentration of triamcinolone used was 2.5 mg/ml or 5 mg/ml according to the pliability score of each scar. RESULTS: The mean number of treatment sessions required to achieve the endpoint was 3.85 +/- 1.25. Among the variables assessed, location of the scar near the sternal notch (P = 0.020) and patient BMI (P = 0.001) were associated with the increasing number of treatment sessions. CONCLUSION: In our study cohort, four treatments were required to reduce the VSS of thyroidectomy scars by 50% when using a combination treatment of CBL and low concentration TA ILI. Also, scar location and patient BMI are factors that affect treatment outcome. PMID- 26149959 TI - Recent and rapid population growth and range expansion of the Lyme disease tick vector, Ixodes scapularis, in North America. AB - Migration is a primary force of biological evolution that alters allele frequencies and introduces novel genetic variants into populations. Recent migration has been proposed as the cause of the emergence of many infectious diseases, including those carried by blacklegged ticks in North America. Populations of blacklegged ticks have established and flourished in areas of North America previously thought to be devoid of this species. The recent discovery of these populations of blacklegged ticks may have resulted from either in situ growth of long-established populations that were maintained at very low densities or by migration and colonization from established populations. These alternative evolutionary hypotheses were investigated using Bayesian phylogeographic approaches to infer the origin and migratory history of recently detected blacklegged tick populations in the Northeastern United States. The data and results indicate that newly detected tick populations are not the product of in situ population growth from a previously established population but from recent colonization resulting in a geographic range expansion. This expansion in the geographic range proceeded primarily through progressive and local migration events from southern populations to proximate northern locations although long distance migration events were also detected. PMID- 26149960 TI - Synthesis and application of isotopically labeled flavin nucleotides. AB - Flavin nucleotides, i.e. flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are utilized as prosthetic groups and/or substrates by a myriad of proteins, ranging from metabolic enzymes to light receptors. Isotopically labeled flavins have served as invaluable tools in probing the structure and function of these flavoproteins. Here we present an enzymatic synthesis of several radio- and stable-isotope labeled flavin nucleotides from commercially available labeled riboflavin and ATP. The synthetic procedure employs a bifunctional enzyme, Corynebacterium ammoniagenes FAD synthetase, that sequentially converts riboflavin to FMN and then to FAD. The final flavin product (FMN or FAD) is controlled by the concentration of ATP in the reaction. Utility of the synthesized labeled FAD cofactors is demonstrated in flavin-dependent thymidylate synthase. The described synthetic approach can be easily applied to the production of flavin nucleotide analogues from riboflavin precursors. PMID- 26149961 TI - Effects of Kinesio taping on scapular kinematics of overhead athletes following muscle fatigue. AB - Scapular kinematics alterations have been found following muscle fatigue. Considering the importance of the lower trapezius in coordinated scapular movement, this study aimed to investigate the effects of elastic taping (Kinesio taping, KT) for muscle facilitation on scapular kinematics of healthy overhead athletes following muscle fatigue. Twenty-eight athletes were evaluated in a crossover, single-blind, randomized design, in three sessions: control (no taping), KT (KT with tension) and sham (KT without tension). Scapular tridimensional kinematics and EMG of clavicular and acromial portions of upper trapezius, lower trapezius and serratus anterior were evaluated during arm elevation and lowering, before and after a fatigue protocol involving repetitive throwing. Median power frequency decline of serratus anterior was significantly lower in KT session compared to sham, possibly indicating lower muscle fatigue. However, the effects of muscle fatigue on scapular kinematics were not altered by taping conditions. Although significant changes were found in scapular kinematics following muscle fatigue, they were small and not considered relevant. It was concluded that healthy overhead athletes seem to present an adaptive mechanism that avoids the disruption of scapular movement pattern following muscle fatigue. Therefore, these athletes do not benefit from the use of KT to assist scapular movement under the conditions tested. PMID- 26149962 TI - Ultrasonography for meniscal injuries in knee joint: a systematic review and meta analysis. AB - INTRODUCTION: The aim of the paper is to systematically review the diagnostic accuracy of ultrasonography for meniscal injuries in knee joint. EVIDENCE ACQUISITION: A search of PubMed and Web of Science was performed up to January 2015. Only studies for diagnosis meniscal injuries by ultrasonography were included. The results were meta-analyzed by pooling estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and constructing the summary receiver operating characteristic (SROC) curves. EVIDENCE SYNTHESIS: Twenty-one studies met the selection criteria for inclusion in the analysis. The pooled estimates for sensitivity, specificity, and area under curve (AUC) of ultrasonography diagnosis were 0.775 (95% CI: 0.747-0.801), 0.838 (95% CI: 0.818-0.857), and 0.9107 (95% CI: 0.8625-0.9589), respectively. For lateral meniscus diagnosis and medial meniscus diagnosis, the AUC was 0.9812 (95% CI: 0.9592-1.000) and 0.8997 (95% CI: 0.7313-1.000), respectively. However, in diagnosis by magnetic resonance imaging (MRI), the AUC was 0.9421 (95% CI: 0.8760-1.000). The ultrasonography inter-observer agreement resulted in a moderate reliability, with the kappa value ranged from 0.381 to 0.482. CONCLUSIONS: We found the diagnostic accuracy of ultrasonography for meniscal injuries was good. No evidence showed MRI had better accuracy than ultrasonography diagnosis. We recommend ultrasonography should be routinely used for evaluation of meniscal injuries in knee joint. PMID- 26149963 TI - A comparison of antioxidative and anti-inflammatory activities of sword beans and soybeans fermented with Bacillus subtilis. AB - This study was conducted to determine the antioxidative and anti-inflammatory activities of non-fermented or Bacillus subtilis-fermented soybeans and sword beans (red and white). The total flavonoid content in both sword bean types was higher (1.9-2.5-fold) than that in soybeans. The total phenolic content in fermented red sword beans was 2.5-fold greater than that in non-fermented red sword beans. HPLC profiles revealed that gallic acid, methyl gallate, and ellagic acid were major phenolic components of non-fermented/fermented red sword beans. DPPH radical scavenging activity and ferric-reducing antioxidant power were higher in fermented red sword beans than in other beans. Non-fermented/fermented red sword beans had higher nitrite scavenging activity than butylated hydroxytoluene and non-fermented/fermented soybeans. The hyaluronidase inhibitory activity of non-fermented/fermented red sword beans was higher (1.5-2.6-fold) than that of non-fermented/fermented soybeans. These results suggest that B. subtilis-fermented sword beans are potential natural antioxidant sources and anti inflammatory agents for the food industry. PMID- 26149964 TI - Imaging early stages of the female reproductive structure of Arabidopsis by confocal laser scanning microscopy. AB - BACKGROUND: The gynoecium is the female reproductive structure and probably the most complex plant structure. During its development, different internal tissues and structures are formed. Insights in gene expression or hormone localization patterns are key to understanding gynoecium development from a molecular biology point of view. RESULTS: Imaging with a confocal laser scanning microscope (CLSM) is a widely used strategy; however, visualization of internal developmental expression patterns in the Arabidopsis gynoecium can be technically challenging. Here, we present a detailed protocol that allows the visualization of internal expression patterns at high resolution during gynoecium development. We demonstrate the applicability using a cytokinin response marker (TCS::GFP), an auxin response marker (DR5::VENUS), and a SEPALLATA3 marker (SEP3::SEP3:GFP). CONCLUSIONS: The detailed protocol presented here allows the visualization of fluorescence signals in internal structures during Arabidopsis gynoecium development. This protocol may also be adapted for imaging other challenging plant structures or organs. PMID- 26149965 TI - Tolterodine in the Treatment of Male LUTS. AB - Storage lower urinary tract symptoms (LUTS) in men are usually chronic, with a high prevalence and a substantial impact on quality of life; therefore, adequate therapies are desirable and crucial for these men. First line treatment for all patients with storage LUTS should always be behavioral. The gold standard for pharmacological treatment of overactive bladder/storage symptoms is a muscarinic receptor antagonist such as tolterodine. First-marketed antimuscarinics were limited by several adverse events such as dry mouth, constipation, tachycardia, accommodation disorder, and cognitive dysfunction, resulting in poor compliance and early treatment discontinuation in a large number of patients. In order to improve compliance with oral drug treatment, tolterodine was developed, providing a better efficacy/adverse event profile. Tolterodine is available in the following two formulations: the intermediate release (IR) and extended release form (ER). Tolterodine ER 4 mg administered once daily is pharmacokinetically equivalent to tolterodine IR 2 mg twice daily but has a lower incidence of adverse events and increased efficacy. Combination therapy of tolterodine and an alpha-blocker is significantly more efficacious than either monotherapy. Even when compared and added to tamsulosin, tolterodine shows a good safety profile. The incidence of acute urinary retention requiring catheterization and treatment withdrawals due to adverse events are low in all the studies included in the present review. PMID- 26149966 TI - Reliability and validity of OSCE checklists used to assess the communication skills of undergraduate medical students: A systematic review. AB - OBJECTIVES: To explore inter-rater agreement between reviewers comparing reliability and validity of checklist forms that claim to assess the communication skills of undergraduate medical students in Objective Structured Clinical Examinations (OSCEs). METHODS: Papers explaining rubrics of OSCE checklist forms were identified from Pubmed, Embase, PsycINFO, and the ProQuest Education Databases up to 2013. Included were those studies that report empirical validity or reliability values for the communication skills assessment checklists used. Excluded were those papers that did not report reliability or validity. RESULTS: Papers focusing on generic communication skills, history taking, physician-patient communication, interviewing, negotiating treatment, information giving, empathy and 18 other domains (ICC -0.12-1) were identified. Regarding the validity and reliability of the communication skills checklists, agreement between reviewers was 0.45. CONCLUSIONS: Heterogeneity in the rubrics used in the assessment of communication skills and a lack of agreement between reviewers makes comparison of student competences within and across institutions difficult. PRACTICE IMPLICATIONS: Consideration should be afforded to the adoption of a standardized measurement instrument to assess communication skills in undergraduate medical education. Future research will focus upon evaluating the potential impact of adoption of a standardized measurement instrument. PMID- 26149967 TI - Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-beta cyclodextrin: Involvement of p53 and Fas receptor ligand complex. AB - Doxorubicin (DOX) is one of the preferred drugs for treating breast and liver cancers. However, its clinical application is limited due to severe side effects and the accompanying drug resistance. In this context, we investigated the effect on therapeutic efficacy of DOX by cholesterol depleting agent methyl-beta cyclodextrin (MCD), and explored the involvement of p53. MCD sensitizes MCF-7 and Hepa1-6 cells to DOX, Combination of MCD and marginal dose of DOX reduces the cell viability, and promoted apoptosis through induction of pro-apoptotic protein, Bax, activation of caspase-8 and caspase-7, down regulation of anti apoptotic protein Bcl-2 and finally promoting PARP cleavage. Mechanistically, sensitization to DOX by MCD was due to the induction of FasR/FasL pathway through p53 activation. Furthermore, inhibition of p53 by pharmacological inhibitor pifithrin-alpha (PFT-alpha) or its specific siRNA attenuated p53 function and down-regulated FasR/FasL, thereby preventing cell death. Animal experiments were performed using C57BL/6J mouse isografted with Hepa1-6 cells. Tumor growth was retarded and survival increased in mice administered MCD together with DOX to as compared to either agent alone. Collectively, these results suggest that MCD enhances the sensitivity to DOX for which wild type p53 is an important determinant. PMID- 26149968 TI - Limbal Basal Cell Density Decreases in Limbal Stem Cell Deficiency. AB - PURPOSE: To investigate changes in limbal basal epithelial cell density in eyes with limbal stem cell deficiency (LSCD) using in vivo confocal laser scanning microscopy. DESIGN: Retrospective observational comparative study. METHODS: A total of 43 eyes of 30 patients diagnosed with LSCD were included in the study. Ten eyes from normal subjects were included as control. Confocal imaging of the central cornea, and the superior, nasal, inferior and temporal limbus were collected using the Heidelberg Retina Tomograph III Rostock Corneal Module. Basal cell density in all locations was measured by 2 independent observers. RESULTS: The mean basal cell density of the normal group was 9264 +/- 598 cells/mm(2) in the cornea and 7120 +/- 362 cells/mm(2) in the limbus. In the LSCD group, the mean basal cell density in the cornea decreased 31.0% (6389 +/- 1820 cells/mm(2), P < .001) and in the limbus decreased 23.6% (5440 +/- 1123 cells/mm(2), P < .001) compared to that in the control. There was a trend of basal cell density decline in more advanced stages of LSCD. The basal cell density declined in the unaffected regions at a similar degree as that in the affected region in sectoral LSCD (P > .05). The basal cell diameter increased by 24.6% in the cornea (14.7 MUm) and by 15.7% in the limbus (15.5 MUm) compared to the control. CONCLUSIONS: Basal cell density in both central cornea and limbus decreases in LSCD. Limbal stem cells (LSCs) are affected globally and basal cell density could be used as a parameter to measure LSC function at the early stages of the disease process. PMID- 26149969 TI - Corneal Collagen Cross-linking for the Treatment of Progressive Corneal Ectasia: 6-Year Prospective Outcome in a French Population. AB - PURPOSE: To evaluate 6-year results of standardized epithelium-off corneal collagen cross-linking (CXL) for treatment of progressive corneal ectasia. DESIGN: Prospective, consecutive, interventional case series. METHODS: Thirty-six eyes of 25 consecutive patients with documented progressive primary or iatrogenic corneal ectasia underwent CXL following the Siena protocol. The main outcome measures included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, biomicroscopy and fundus appearance, topography-derived steep and flat keratometry (Kmax, Kmin), central corneal thickness (CCT), intraocular pressure with Goldmann applanation tonometer (GAT-IOP), and endothelial cell density (ECD), recorded at baseline and months 1, 3, 6, 12, 24, 36, and 72. Bilateral macular optical coherence tomography was performed at the endpoint visit. The mean follow-up was 66 +/- 6 months (range, 60-78 months). RESULTS: At 6 years, CXL stabilized primary and iatrogenic corneal ectasia in 89% of the patients. In bilateral CXL, the progression of the first eye was highly predictive of the fellow eye's outcome. At the endpoint follow-up, the mean outcome variations were: UDVA: -0.08 +/- 0.36 logMAR (P = .2); CDVA: -0.14 +/- 0.28 logMAR (P = .004); Kmax: +0.11 +/- 1.70 diopters (D) (P = .7); Kmin: -0.25 +/- 1.25 D (P = .2); CCT: -16.38 +/- 37 MUm (P = .01); GAT-IOP: +1.0 +/- 2.3 mm Hg (P = .01); ECD: +31 +/- 400 cells/mm(2) (P = .6); no cases of macular toxicity or severe adverse events were reported. CONCLUSIONS: At 6 years, CXL maintains long-term results in halting the progression of corneal ectasia, with significant improvement in CDVA and long-term stability of keratometry. Further clinical studies with longer follow-up and larger series would be necessary to definitely confirm these results. PMID- 26149970 TI - Physical properties of different orthodontic cements. AB - INTRODUCTION: We evaluated the water absorption, solubility, and compressive strength of different cements and resin-modified glass ionomer cements (RMGICs), namely Adhesor(r), Ketac(TM) Cem, Ortho Band Paste LC(TM), Glass Ionomer Band Cement, and Transbond(TM) Plus. Our aims were to compare the mechanical and physical properties of the cements widely used in orthodontics and to define the most suitable cements in an oral environment in terms of those characteristics. MATERIALS AND METHODS: To assess compressive strength, the cements were subjected to compression tests done on a universal testing machine. To test water absorption and solubility, the weight changes in cement specimens were determined after immersion in distilled water for 1, 7, and 30 days. RESULTS: Adhesor(r) and Ketac(TM) Cem presented significantly higher solubility values than other cements after water immersion for 1, 7, and 30 days (p < 0.001). CONCLUSION: Our results revealed that the traditional orthodontic cements have higher water solubility and water absorption values as well as lower compressive strength values than the RMGICs used in this study. Furthermore, Transbond(TM) Plus revealed the highest compressive strength, whereas Adhesor(r) showed the lowest. PMID- 26149971 TI - Effectiveness of two different splints to treat temporomandibular disorders. AB - Nearly 5% of the the world's population has temporomandibular disorder (TMD) severe enough to make them seek treatment. A third of the total population has at least one TMD symptom. There are different types of splints to treat TMD. In our study, we compared the success of two different appliances [stabilization splint (ss), nociceptive trigeminal inhibition splint (NTI)] by using Fonseca's questionnaire, the OHQoL-UK and visual analog scale (VAS). A total of 40 patients suffering from TMD were included in this study and answered questionnaires twice, at the beginning of the treatment and 3 months later. Regarding TMD alone, 39 patients (97.5%) had some degree of the disorder, 7 of of these cases being mild (17.5%), 15 moderate (37.5%), and 17 severe (42.5%). We analyzed posttreatment changes compared to baseline. Pain complaints decreased in both groups, and the OHQoL-UK revealed better quality of life after treatment. Based on the posttreatment Fonseca's questionnaires, significant changes in the patients' complaints in the group SS (p < 0.01) were observed. The group NTI also displayed changes but these were not statistically significant after treatment (p > 0.05). Patients in both groups had fewer TMD complaints after TMJ treatment. According to the Fonseca's questionnaire, the patients' major TMD complaint was clenching grinding, followed by pain in the craniomandibular joint, or earache. PMID- 26149972 TI - Experimental drought and heat can delay phenological development and reduce foliar and shoot growth in semiarid trees. AB - Higher temperatures associated with climate change are anticipated to trigger an earlier start to the growing season, which could increase the terrestrial C sink strength. Greater variability in the amount and timing of precipitation is also expected with higher temperatures, bringing increased drought stress to many ecosystems. We experimentally assessed the effects of higher temperature and drought on the foliar phenology and shoot growth of mature trees of two semiarid conifer species. We exposed field-grown trees to a ~45% reduction in precipitation with a rain-out structure ('drought'), a ~4.8 degrees C temperature increase with open-top chambers ('heat'), and a combination of both simultaneously ('drought + heat'). Over the 2013 growing season, drought, heat, and drought + heat treatments reduced shoot and needle growth in pinon pine (Pinus edulis) by >=39%, while juniper (Juniperus monosperma) had low growth and little response to these treatments. Needle emergence on primary axis branches of pinon pine was delayed in heat, drought, and drought + heat treatments by 19-57 days, while secondary axis branches were less likely to produce needles in the heat treatment, and produced no needles at all in the drought + heat treatment. Growth of shoots and needles, and the timing of needle emergence correlated inversely with xylem water tension and positively with nonstructural carbohydrate concentrations. Our findings demonstrate the potential for delayed phenological development and reduced growth with higher temperatures and drought in tree species that are vulnerable to drought and reveal potential mechanistic links to physiological stress responses. Climate change projections of an earlier and longer growing season with higher temperatures, and consequent increases in terrestrial C sink strength, may be incorrect for regions where plants will face increased drought stress with climate change. PMID- 26149973 TI - Assessing the Representativeness of Medical Expenditure Panel Survey Inpatient Utilization Data for Individuals With Psychiatric and Nonpsychiatric Conditions. AB - Sampling and reporting biases in the Medical Expenditure Panel Survey (MEPS) survey could render data on inpatient utilization that are not representative for individuals with severe psychiatric conditions. The authors assessed the representativeness of MEPS data on psychiatric inpatient utilization, by comparing MEPS estimates of total annual psychiatric and nonpsychiatric inpatient admissions and bed days, and mean length of stay, for nonelderly U.S. adults in calendar years 2005 to 2010 (N = 9,288) to estimates from the Nationwide Inpatient Sample (NIS), a nationally representative inpatient care database derived from hospitals' administrative records (N = 21,934,378). Compared with the NIS, the MEPS indicated 34% as many psychiatric admissions and 86% as many nonpsychiatric admissions, while mean psychiatric length of stay was greater in MEPS than in NIS. In MEPS data, underrepresentation of psychiatric inpatient utilization at community hospitals may result in measurement distortions for commonly used statistics on psychiatric inpatient utilization and costs. PMID- 26149974 TI - Recent Progress on Flexible Triboelectric Nanogenerators for SelfPowered Electronics. AB - Recently, smart systems have met with large success. At the origin of the internet of things, they are a key driving force for the development of wireless, sustainable, and independent autonomous smart systems. In this context, autonomy is critical, and despite all the progress that has been made in low-power electronics and batteries, energy harvesters are becoming increasingly important. Thus, harvesting mechanical energy is essential, as it is widespread and abundant in our daily life environment. Among harvesters, flexible triboelectric nanogenerators (TENGs) exhibit good performance, and they are easy to integrate, which makes them perfect candidates for many applications and, therefore, crucial to develop. In this review paper, we first introduce the fundamentals of TENGs, including their four basic operation modes. Then, we discuss the different improvement parameters. We review some progress made in terms of performance and integration that have been possible through the understanding of each operation mode and the development of innovative structures. Finally, we present the latest trends, structures, and materials in view of future improvements and applications. PMID- 26149975 TI - Genetics of human isolated hereditary nail disorders. AB - Human hereditary nail disorders constitute a rare and heterogeneous group of ectodermal dysplasias. They occur as isolated and/or syndromic ectodermal conditions where other ectodermal appendages are also involved, and can occur associated with skeletal dysplasia. 'Nail disorder, nonsyndromic congenital' (OMIM; Online Mendelian Inheritance in Man) is subclassified into 10 different types. The underlying genes identified thus far are expressed in the nail bed and play important roles in nail development and morphogenesis. Here, we review the current literature on nail disorders and present a coherent review on the genetics of nail disorders. This review will pave the way to identifying putative genes and pathways involved in nail development and morphogenesis. PMID- 26149976 TI - Spectroscopic and second-order nonlinear optical properties of Ruthenium(ii) complexes: a DFT/MRCI and ADC(2) study. AB - In this communication we use the density functional theory-based multi-reference configuration interaction (DFT/MRCI) and the second-order algebraic diagrammatic construction (ADC(2)) methods to compute the spectroscopic and second-order nonlinear optical (NLO) properties of Ru(ii)-based NLO-phores. For some of the complexes, an appropriate treatment of doubly excited states is essential to correctly describe their spectroscopic and photochemical properties. Geometrical and solvent relaxation effects are also assessed. An adequate treatment of solvent effects seems critical for an accurate description of the NLO properties of these complexes. PMID- 26149977 TI - Response and inbreeding from a genomic selection experiment in layer chickens. AB - BACKGROUND: Genomic selection (GS) using estimated breeding values (GS-EBV) based on dense marker data is a promising approach for genetic improvement. A simulation study was undertaken to illustrate the opportunities offered by GS for designing breeding programs. It consisted of a selection program for a sex limited trait in layer chickens, which was developed by deterministic predictions under different scenarios. Later, one of the possible schemes was implemented in a real population of layer chicken. METHODS: In the simulation, the aim was to double the response to selection per year by reducing the generation interval by 50 %, while maintaining the same rate of inbreeding per year. We found that GS with retraining could achieve the set objectives while requiring 75 % fewer reared birds and 82 % fewer phenotyped birds per year. A multi-trait GS scenario was subsequently implemented in a real population of brown egg laying hens. The population was split into two sub-lines, one was submitted to conventional phenotypic selection, and one was selected based on genomic prediction. At the end of the 3-year experiment, the two sub-lines were compared for multiple performance traits that are relevant for commercial egg production. RESULTS: Birds that were selected based on genomic prediction outperformed those that were submitted to conventional selection for most of the 16 traits that were included in the index used for selection. However, although the two programs were designed to achieve the same rate of inbreeding per year, the realized inbreeding per year assessed from pedigree was higher in the genomic selected line than in the conventionally selected line. CONCLUSIONS: The results demonstrate that GS is a promising alternative to conventional breeding for genetic improvement of layer chickens. PMID- 26149979 TI - Parkinson disease: Disease-linked morphometric variants of alpha-synuclein. PMID- 26149980 TI - Improved diagnostic sensitivity can aid the correct choice of treatment for patients with myasthenia gravis. PMID- 26149978 TI - Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process. AB - The clinical use of MRI in patients with multiple sclerosis (MS) has advanced markedly over the past few years. Technical improvements and continuously emerging data from clinical trials and observational studies have contributed to the enhanced performance of this tool for achieving a prompt diagnosis in patients with MS. The aim of this article is to provide guidelines for the implementation of MRI of the brain and spinal cord in the diagnosis of patients who are suspected of having MS. These guidelines are based on an extensive review of the recent literature, as well as on the personal experience of the members of the MAGNIMS (Magnetic Resonance Imaging in MS) network. We address the indications, timing, coverage, reporting and interpretation of MRI studies in patients with suspected MS. Our recommendations are intended to help radiologists and neurologists standardize and optimize the use of MRI in clinical practice for the diagnosis of MS. PMID- 26149981 TI - Kallistatin ameliorates influenza virus pathogenesis by inhibition of kallikrein related peptidase 1-mediated cleavage of viral hemagglutinin. AB - Proteolytic cleavage of the hemagglutinin (HA) of influenza virus by host trypsin like proteases is required for viral infectivity. Some serine proteases are capable of cleaving influenza virus HA, whereas some serine protease inhibitors (serpins) inhibit the HA cleavage in various cell types. Kallikrein-related peptidase 1 (KLK1, also known as tissue kallikrein) is a widely distributed serine protease. Kallistatin, a serpin synthesized mainly in the liver and rapidly secreted into the circulation, forms complexes with KLK1 and inhibits its activity. Here, we investigated the roles of KLK1 and kallistatin in influenza virus infection. We show that the levels of KLK1 increased, whereas those of kallistatin decreased, in the lungs of mice during influenza virus infection. KLK1 cleaved H1, H2, and H3 HA molecules and consequently enhanced viral production. In contrast, kallistatin inhibited KLK1-mediated HA cleavage and reduced viral production. Cells transduced with the kallistatin gene secreted kallistatin extracellularly, which rendered them more resistant to influenza virus infection. Furthermore, lentivirus-mediated kallistatin gene delivery protected mice against lethal influenza virus challenge by reducing the viral load, inflammation, and injury in the lung. Taking the data together, we determined that KLK1 and kallistatin contribute to the pathogenesis of influenza virus by affecting the cleavage of the HA peptide and inflammatory responses. This study provides a proof of principle for the potential therapeutic application of kallistatin or other KLK1 inhibitors for influenza. Since proteolytic activation also enhances the infectivity of some other viruses, kallistatin and other kallikrein inhibitors may be explored as antiviral agents against these viruses. PMID- 26149982 TI - Identification and characterization of a novel family of selective antifungal compounds (CANBEFs) that interfere with fungal protein synthesis. AB - Invasive mycotic infections have become more common during recent decades, posing an increasing threat to public health. However, despite the growing needs, treatments for invasive fungal infections remain unsatisfactory and are limited to a small number of antifungals. The aim of this study was to identify novel fungal cell wall inhibitors from a library of small chemical compounds using a conditional protein kinase C (PKC)-expressing strain of Aspergillus nidulans sensitive to cell wall-active agents. Eight "hit" compounds affecting cell wall integrity were identified from a screen of 35,000 small chemical compounds. Five shared a common basic molecular structure of 4-chloro-6-arylamino-7-nitro benzofurazane (CANBEF). The most potent compound, CANBEF-24, was characterized further and was shown to inhibit the growth of pathogenic Aspergillus, Candida, Fusarium, and Rhizopus isolates at micromolar concentrations but not to affect the growth of mammalian cell lines. CANBEF-24 demonstrated strong synergy in combination with caspofungin, an antifungal that inhibits cell wall biosynthesis. Genetic and biochemical analyses with Aspergillus nidulans and Saccharomyces cerevisiae indicated that CANBEFs selectively inhibit fungal rRNA maturation and protein synthesis, suggesting that their effect on the cell wall is indirect. CANBEFs were nontoxic in insect (Galleria mellonella, Drosophila melanogaster) and mouse models of fungal infection. Preliminary evidence showing no therapeutic benefit in these models suggests that further cycles of optimization are needed for the development of this novel class of compounds for systemic use. PMID- 26149983 TI - Characterization of HIV-1 Resistance to Tenofovir Alafenamide In Vitro. AB - Tenofovir alafenamide (TAF) is an investigational prodrug of the HIV-1 nucleotide reverse transcriptase (RT) inhibitor (NtRTI) tenofovir (TFV), with improved potency and drug delivery properties over the current prodrug, tenofovir disoproxil fumarate (TDF). TAF is currently in phase 3 clinical studies for the treatment of HIV-1 infection, in combination with other antiretroviral agents. Phase 1 and 2 studies have shown that TAF was associated with increased peripheral blood mononuclear cell (PBMC) drug loading and increased suppression of HIV-1 replication compared to treatment with TDF. In this study, selection of in vitro resistance to both TAF and the parent compound, TFV, led to the emergence of HIV-1 with the K65R amino acid substitution in RT with 6.5-fold reduced susceptibility to TAF. Although TAF is more potent than TFV in vitro, the antiviral susceptibilities to TAF and TFV of a large panel of nucleoside/nucleotide RT inhibitor (NRTI)-resistant mutants were highly correlated (R(2) = 0.97), indicating that the two compounds have virtually the same resistance profile when assessed as fold change from the wild type. TAF showed full antiviral activity in PBMCs against primary HIV-1 isolates with protease inhibitor, nonnucleoside RT inhibitor (NNRTI), or integrase strand transfer inhibitor resistance but reduced activity against isolates with extensive NRTI resistance amino acid substitutions. However, the increased cell loading of TFV with TAF versus TDF observed in vivo suggests that TAF may retain activity against TDF-resistant mutant viruses. PMID- 26149984 TI - Contrasting ex vivo efficacies of "reversed chloroquine" compounds in chloroquine resistant Plasmodium falciparum and P. vivax isolates. AB - Chloroquine (CQ) has been the mainstay of malaria treatment for more than 60 years. However, the emergence and spread of CQ resistance now restrict its use to only a few areas where malaria is endemic. The aim of the present study was to investigate whether a novel combination of a CQ-like moiety and an imipramine like pharmacophore can reverse CQ resistance ex vivo. Between March to October 2011 and January to September 2013, two "reversed chloroquine" (RCQ) compounds (PL69 and PL106) were tested against multidrug-resistant field isolates of Plasmodium falciparum (n = 41) and Plasmodium vivax (n = 45) in Papua, Indonesia, using a modified ex vivo schizont maturation assay. The RCQ compounds showed high efficacy against both CQ-resistant P. falciparum and P. vivax field isolates. For P. falciparum, the median 50% inhibitory concentrations (IC50s) were 23.2 nM for PL69 and 26.6 nM for PL106, compared to 79.4 nM for unmodified CQ (P < 0.001 and P = 0.036, respectively). The corresponding values for P. vivax were 19.0, 60.0, and 60.9 nM (P < 0.001 and P = 0.018, respectively). There was a significant correlation between IC50s of CQ and PL69 (Spearman's rank correlation coefficient [r s] = 0.727, P < 0.001) and PL106 (rs = 0.830, P < 0.001) in P. vivax but not in P. falciparum. Both RCQs were equally active against the ring and trophozoite stages of P. falciparum, but in P. vivax, PL69 and PL106 showed less potent activity against trophozoite stages (median IC50s, 130.2 and 172.5 nM) compared to ring stages (median IC50s, 17.6 and 91.3 nM). RCQ compounds have enhanced ex vivo activity against CQ-resistant clinical isolates of P. falciparum and P. vivax, suggesting the potential use of reversal agents in antimalarial drug development. Interspecies differences in RCQ compound activity may indicate differences in CQ pharmacokinetics between the two Plasmodium species. PMID- 26149985 TI - Leishmanicidal activities of novel methylseleno-imidocarbamates. AB - The generation of new antileishmanial drugs has become a priority. Selenium and its derivatives stand out as having promising leishmanicidal activity. In fact, some parasites express selenoproteins and metabolize selenium. Recently, selenium derivatives have shown the potential to reduce parasitemia, clinical manifestations, and mortality in parasite-infected mice. In this paper, after selecting four candidates according to drug similarity parameters, we observed that two of them, called compounds 2b [methyl-N,N'-di(thien-2-ylcarbonyl) imidoselenocarbamate] and 4b [methyl-N,N'-di(5-nitrothien-3-ylcarbonyl) imidoselenocarbamate], exhibit low 50% inhibitory concentrations (IC50s) (<3 MUM) and good selectivity indexes (SIs) (>5) in Leishmania major promastigotes and lack toxicity on macrophages. In addition, in analysis of their therapeutic potential against L. major in vitro infection, both compounds display a dramatic reduction of amastigote burden (~80%) with sublethal concentrations. Furthermore, in macrophages, these selenocompounds induce nitric oxide production, which has been described to be critical for defense against intracellular pathogens. Compounds 2b and 4b were demonstrated to cause cell cycle arrest in G1. Interestingly, evaluation of expression of genes related to proliferation (PCNA), treatment resistance (ABC transporter and alpha-tubulin), and virulence (quinonoid dihydropteridine reductase [QDPR]) showed several alterations in gene expression profiling. All these results prompt us to propose both compounds as candidates to treat leishmanial infections. PMID- 26149986 TI - Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum. AB - Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID- 26149987 TI - Population pharmacokinetic modeling of itraconazole and hydroxyitraconazole for oral SUBA-itraconazole and sporanox capsule formulations in healthy subjects in fed and fasted states. AB - Itraconazole is an orally active antifungal agent that has complex and highly variable absorption kinetics that is highly affected by food. This study aimed to develop a population pharmacokinetic model for itraconazole and the active metabolite hydroxyitraconazole, in particular, quantifying the effects of food and formulation on oral absorption. Plasma pharmacokinetic data were collected from seven phase I crossover trials comparing the SUBA-itraconazole and Sporanox formulations of itraconazole. First, a model of single-dose itraconazole data was developed, which was then extended to the multidose data. Covariate effects on itraconazole were then examined before extending the model to describe hydroxyitraconazole. The final itraconazole model was a 2-compartment model with oral absorption described by 4-transit compartments. Multidose kinetics was described by total effective daily dose- and time-dependent changes in clearance and bioavailability. Hydroxyitraconazole was best described by a 1-compartment model with mixed first-order and Michaelis-Menten elimination for the single-dose data and a time-dependent clearance for the multidose data. The relative bioavailability of SUBA-itraconazole compared to that of Sporanox was 173% and was 21% less variable between subjects. Food resulted in a 27% reduction in bioavailability and 58% reduction in the transit absorption rate constant compared to that with the fasted state, irrespective of the formulation. This analysis presents the most extensive population pharmacokinetic model of itraconazole and hydroxyitraconazole in the literature performed in healthy subjects. The presented model can be used for simulating food effects on itraconazole exposure and for performing prestudy power analysis and sample size estimation, which are important aspects of clinical trial design of bioequivalence studies. PMID- 26149988 TI - Effective Sequestration of Clostridium difficile Protein Toxins by Calcium Aluminosilicate. AB - Clostridium difficile is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for C. difficile infection. Toxin A (TcdA) and toxin B (TcdB) are nearly indispensable virulence factors for Clostridium difficile pathogenesis. Given the toxin-centric mechanism by which C. difficile pathogenesis occurs, the selective sequestration with neutralization of TcdA and TcdB by nonantibiotic agents represents a novel mode of action to prevent or treat C. difficile-associated disease. In this preclinical study, we used quantitative enzyme immunoassays to determine the extent by which a novel drug, calcium aluminosilicate uniform particle size nonswelling M-1 (CAS UPSN M-1), is capable of sequestering TcdA and TcdB in vitro. The following major findings were derived from the present study. First, we show that CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Second, we show that CAS UPSN M-1's affinity for TcdA is greater than its affinity for TcdB. Last, we show that CAS UPSN M-1 exhibited limited binding affinity for nontarget proteins. Taken together, these results suggest that ingestion of calcium aluminosilicate might protect gastrointestinal tissues from antibiotic- or chemotherapy-induced C. difficile infection by neutralizing the cytotoxic and proinflammatory effects of luminal TcdA and TcdB. PMID- 26149989 TI - SR-2P vaginal microbicide gel provides protection against herpes simplex virus 2 when administered as a combined prophylactic and postexposure therapeutic. AB - Previously, we demonstrated that a single prophylactic dose of SR-2P, a novel dual-component microbicide gel comprising acyclovir and tenofovir, led to a modest increase in mouse survival following a lethal challenge of herpes simplex virus 2 (HSV-2). Here, we show that a dose of SR-2P administered 24 h prior to infection provides some protection against the virus, but to a lesser degree than SR-2P administered either once a day for 2 days or 1 h prior to infection. None of the prophylactic doses blocked infection by the virus, and all resulted in 80 to 100% lethality. However, given that a prophylactic dose still provided a significant reduction in overall clinical score, reduced rate of body weight loss, and increased median survival of the mice, we examined whether a repetitive dose regimen (postinfection) in addition to the prophylactic dose could prevent death and reduce the levels of virus in mice. Nearly all (9 of 10 in each group) of the mice that received SR-2P for 2 days prior to infection or that received SR 2P 1 h prior to infection and were administered SR-2P once a day for 10 days after infection showed no clinical symptoms of infection and no viral loads in vaginal swabs and survived for 28 days postinfection. Conversely, mice receiving no treatment or an identical vehicle treatment demonstrated advanced clinical signs and did not survive past day 9 postinfection. We conclude that SR-2P is an effective anti-HSV-2 agent in mice. PMID- 26149990 TI - Protective effect of ginsenosides Rg1 and Re on lipopolysaccharide-induced sepsis by competitive binding to Toll-like receptor 4. AB - We previously demonstrated that ginsenosides Rg1 and Re enhanced the immune response in C3H/HeB mice but not in C3H/HeJ mice carrying a mutation in the Tlr4 gene. The results of the present study showed that both Rg1 and Re inhibited mRNA expression and production of proinflammatory mediators that included tumor necrosis factor alpha, interleukin-1beta, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase from lipopolysaccharide (LPS)-stimulated macrophages. Rg1 was found to be distributed both extracellularly and intracellularly but Re was located only extracellularly to compete with LPS for binding to Toll-like receptor 4. Preinjection of Rg1 and Re into rats suppressed LPS-induced increases in body temperature, white blood cell counts, and levels of serum proinflammatory mediators. Preinjection of Rg1 and Re into mice prevented the LPS-induced decreases in total white blood cell counts and neutrophil counts, inhibited excessive expression of multiple proinflammatory mediators, and successfully rescued 100% of the mice from sepsis-associated death. More significantly, when administered after lethal LPS inoculation, Rg1, but not Re, still showed a potent antisepsis effect and protected 90% of the mice from death. The better protection efficacy of Rg1 could result from its intracellular distribution, suggesting that Rg1 may be an ideal antisepsis agent. PMID- 26149991 TI - A cfr-like gene from Clostridium difficile confers multiple antibiotic resistance by the same mechanism as the cfr gene. AB - The Cfr RNA methyltransferase causes multiple resistances to peptidyl transferase inhibitors by methylation of A2503 23S rRNA. Many cfr-like gene sequences in the databases code for unknown functions. This study confirms that a Cfr-like protein from a Peptoclostridium difficile (formerly Clostridium difficile) strain does function as a Cfr protein. The enzyme is expressed in Escherichia coli and shows elevated MICs for five classes of antibiotics. A primer extension stop indicates a modification at A2503 in 23S rRNA. PMID- 26149992 TI - In Vitro Virology Profile of Tenofovir Alafenamide, a Novel Oral Prodrug of Tenofovir with Improved Antiviral Activity Compared to That of Tenofovir Disoproxil Fumarate. AB - Tenofovir alafenamide (TAF) is an investigational oral prodrug of the HIV-1 nucleotide reverse transcriptase inhibitor tenofovir (TFV). Tenofovir disoproxil fumarate (TDF) is another TFV prodrug, widely used for the treatment of HIV-1 infection. TAF is converted mostly intracellularly to TFV and, in comparison to TDF, achieves higher tenofovir diphosphate (TFV-DP) levels in peripheral blood mononuclear cells. As a result, TAF has demonstrated potent anti-HIV-1 activity at lower doses than TDF in monotherapy studies. Here, the in vitro virology profile of TAF was evaluated and compared to that of TDF. TAF displayed potent antiviral activity against all HIV-1 groups/subtypes, as well as HIV-2. TAF exhibited minimal changes in the drug concentration needed to inhibit 50% of viral spread (EC50) upon removal of the prodrug, similar to TDF, demonstrating intracellular antiviral persistence. While TAF and TDF exhibited comparable potencies in the absence of serum pretreatment, TAF maintained activity in the presence of human serum, whereas TDF activity was significantly reduced. This result demonstrates TAF's improved plasma stability over TDF, which is driven by the different metabolic pathways of the two prodrugs and is key to TAF's improved in vivo antiviral activity. The activity of TAF is specific for HIV, as TAF lacked activity against a large panel of human viruses, with the exception of herpes simplex virus 2, where weak TAF antiviral activity was observed, as previously observed with TFV. Finally, in vitro combination studies with antiretroviral drugs from different classes showed additive to synergistic interactions with TAF, consistent with ongoing clinical studies with TAF in fixed dose combinations with multiple other antiretroviral drugs for the treatment of HIV. PMID- 26149993 TI - Determination of bedaquiline in human serum using liquid chromatography-tandem mass spectrometry. AB - Bedaquiline, a diarylquinoline for the treatment of multidrug-resistant tuberculosis (TB), relies on exposure-dependent killing. As data on drug exposure in specific populations are scarce, pharmacokinetic studies may be of interest. No simple and robust validated liquid chromatography-tandem mass spectrometry (LC MS/MS) method has been reported to date. Therefore, a new method using a quadrupole mass spectrometer was developed for analysis of bedaquiline and N monodesmethyl bedaquiline (M2) in human serum, using deuterated bedaquiline as the internal standard. The calibration curve was linear over a range of 0.05 (lower limit of quantification [LLOQ]) to 6.00 mg/liter for both bedaquiline and M2, with correlation coefficient values of 0.997 and 0.999, respectively. The calculated accuracy ranged from 1.9% to 13.6% for bedaquiline and 2.9% to 8.5% for M2. Within-run precision ranged from 3.0% to 7.2% for bedaquiline and 3.1% to 5.2% for M2, and between-run precision ranged from 0.0% to 4.3% for bedaquiline and 0.0% to 4.6% for M2. Evaluation of serum concentrations in a patient receiving bedaquiline showed high levels at the end of treatment, reflecting accumulation of the drug. More observational pharmacokinetic data are needed to relate altered drug concentrations to clinical outcome or adverse drug effects. A simple LC-MS/MS method to quantify bedaquiline and M2 levels in human serum using a deuterated internal standard has been validated. This method can be used in clinical studies and daily practice. PMID- 26149994 TI - AAC(3)-XI, a new aminoglycoside 3-N-acetyltransferase from Corynebacterium striatum. AB - Corynebacterium striatum BM4687 was resistant to gentamicin and tobramycin but susceptible to kanamycin A and amikacin, a phenotype distinct among Gram-positive bacteria. Analysis of the entire genome of this strain did not detect any genes for known aminoglycoside resistance enzymes. Yet, annotation of the coding sequences identified 12 putative acetyltransferases or GCN5-related N acetyltransferases. A total of 11 of these coding sequences were also present in the genomes of other Corynebacterium spp. The 12th coding sequence had 55 to 60% amino acid identity with acetyltransferases in Actinomycetales. The gene was cloned in Escherichia coli, where it conferred resistance to aminoglycosides by acetylation. The protein was purified to homogeneity, and its steady-state kinetic parameters were determined for dibekacin and kanamycin B. The product of the turnover of dibekacin was purified, and its structure was elucidated by high field nuclear magnetic resonance (NMR), indicating transfer of the acetyl group to the amine at the C-3 position. Due to the unique profile of the reaction, it was designated aminoglycoside 3-N-acetyltransferase type XI. PMID- 26149995 TI - In silico-based high-throughput screen for discovery of novel combinations for tuberculosis treatment. AB - There are currently 18 drug classes for the treatment of tuberculosis, including those in the development pipeline. An in silico simulation enabled combing the innumerably large search space to derive multidrug combinations. Through the use of ordinary differential equations (ODE), we constructed an in silico kinetic platform in which the major metabolic pathways in Mycobacterium tuberculosis and the mechanisms of the antituberculosis drugs were integrated into a virtual proteome. The optimized model was used to evaluate 816 triplets from the set of 18 drugs. The experimentally derived cumulative fractional inhibitory concentration (?FIC) value was within twofold of the model prediction. Bacterial enumeration revealed that a significant number of combinations that were synergistic for growth inhibition were also synergistic for bactericidal effect. The in silico-based screen provided new starting points for testing in a mouse model of tuberculosis, in which two novel triplets and five novel quartets were significantly superior to the reference drug triplet of isoniazid, rifampin, and ethambutol (HRE) or the quartet of HRE plus pyrazinamide (HREZ). PMID- 26149996 TI - Population approach to analyze the pharmacokinetics of free and total lopinavir in HIV-infected pregnant women and consequences for dose adjustment. AB - The aims of this study were to describe the unbound and total lopinavir (LPV) pharmacokinetics in pregnant women in order to evaluate if a dosing adjustment is necessary during pregnancy. Lopinavir placental transfer is described, and several genetic covariates were tested to explain its variability. A total of 400 maternal, 79 cord blood, and 48 amniotic fluid samples were collected from 208 women for LPV concentration determinations and pharmacokinetics analysis. Among the maternal LPV concentrations, 79 samples were also used to measure the unbound LPV concentrations. Population pharmacokinetics models were developed by using NONMEM software. Two models were developed to describe (i) unbound and total LPV pharmacokinetics and (ii) LPV placental transfer. The pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. A pregnancy effect was found on maternal clearance (39% increase), whereas the treatment group (monotherapy versus triple therapy) or the genetic polymorphisms did not explain the pharmacokinetics or placental transfer of LPV. Efficient unbound LPV concentrations in nonpregnant women were similar to those measured during the third trimester of pregnancy. Our study showed a 39% increase of maternal total LPV clearance during pregnancy, whereas unbound LPV concentrations were similar to those simulated in nonpregnant women. The genetic polymorphisms selected did not influence the LPV pharmacokinetics or placental transfer. Thus, we suggest that the LPV dosage should not be increased during pregnancy. PMID- 26149997 TI - Hydrolysis of clavulanate by Mycobacterium tuberculosis beta-lactamase BlaC harboring a canonical SDN motif. AB - Combinations of beta-lactams with clavulanate are currently being investigated for tuberculosis treatment. Since Mycobacterium tuberculosis produces a broad spectrum beta-lactamase, BlaC, the success of this approach could be compromised by the emergence of clavulanate-resistant variants, as observed for inhibitor resistant TEM variants in enterobacteria. Previous analyses based on site directed mutagenesis of BlaC have led to the conclusion that this risk was limited. Here, we used a different approach based on determination of the crystal structure of beta-lactamase BlaMAb of Mycobacterium abscessus, which efficiently hydrolyzes clavulanate. Comparison of BlaMAb and BlaC allowed for structure assisted site-directed mutagenesis of BlaC and identification of the G(132)N substitution that was sufficient to switch the interaction of BlaC with clavulanate from irreversible inactivation to efficient hydrolysis. The substitution, which restored the canonical SDN motif (SDG->SDN), allowed for efficient hydrolysis of clavulanate, with a more than 10(4)-fold increase in k cat (0.41 s(-1)), without affecting the hydrolysis of other beta-lactams. Mass spectrometry revealed that acylation of BlaC and of its G(132)N variant by clavulanate follows similar paths, involving sequential formation of two acylenzymes. Decarboxylation of the first acylenzyme results in a stable secondary acylenzyme in BlaC, whereas hydrolysis occurs in the G(132)N variant. The SDN/SDG polymorphism defines two mycobacterial lineages comprising rapidly and slowly growing species, respectively. Together, these results suggest that the efficacy of beta-lactam-clavulanate combinations may be limited by the emergence of resistance. beta-Lactams active without clavulanate, such as faropenem, should be prioritized for the development of new therapies. PMID- 26149999 TI - Productive hours by direct-care providers is the best measure of nurse staffing in relation to patient outcomes. PMID- 26149998 TI - In Vitro Efficacy of Antiviral Compounds against Enterovirus D68. AB - In 2014, the United States experienced a large outbreak of severe respiratory illness associated with enterovirus D68 (EV-D68). We used a homogeneous, cell based assay to assess the antiviral activity of compounds developed for EV/rhinovirus infection or other indications. Three of 15 compounds were highly active against all four strains tested (the prototype and three 2014 strains), with 50% effective concentrations of 0.0012 to 0.027 MUM. Additional studies are needed to assess their in vivo efficacy against EV-D68. PMID- 26150000 TI - Anthropogenically enhanced chemical weathering and carbon evasion in the Yangtze Basin. AB - Chemical weathering is a fundamental geochemical process regulating the atmosphere-land-ocean fluxes and earth's climate. It is under natural conditions driven primarily by weak carbonic acid that originates from atmosphere CO2 or soil respiration. Chemical weathering is therefore assumed as positively coupled with its CO2 consumption in contemporary geochemistry. Strong acids (i.e. sulfuric- and nitric acid) from anthropogenic sources have been found to influence the weathering rate and CO2 consumption, but their integrated effects remain absent in the world largest river basins. By interpreting the water chemistry and overall proton budget in the Yangtze Basin, we found that anthropogenic acidification had enhanced the chemical weathering by 40% during the past three decades, leading to an increase of 30% in solute discharged to the ocean. Moreover, substitution of carbonic acid by strong acids increased inorganic carbon evasion, offsetting 30% of the CO2 consumption by carbonic weathering. Our assessments show that anthropogenic loadings of sulfuric and nitrogen compounds accelerate chemical weathering but lower its CO2 sequestration. These findings have significant relevance to improving our contemporary global biogeochemical budgets. PMID- 26150001 TI - Retrograde guidewire fracture complicated with pericardial tamponade in chronic total occlusive coronary lesion. AB - Along with various coronary devices progress, there is a now growing trend to percutaneous coronary intervention for chronic total occlusion (CTO). However, the risk of guidewire fracture rate might be increased in complex lesion such as tortuous, calcific lesion or retrograde route. We report a case of successful surgical removal of fractured and entrapped guidewire in a septal channel during retrograde CTO intervention in a patient complicated with pericardial tamponade by delayed penetration of broken guidewire into pericardium. PMID- 26150002 TI - A Review of Carbon Dioxide Monitoring During Adult Cardiopulmonary Resuscitation. AB - Although high quality cardiopulmonary resuscitation is one of the most significant factors related to favourable outcome, its quality depends on many components, such as airway management, compression depth and chest recoil, hands off time, and early defibrillation. The most common way of controlling the resuscitation efforts is monitoring of end-tidal carbon dioxide. The International Liaison Committee on Resuscitation suggests this method both for in hospital and out-of-hospital cardiac arrest. However, despite the abundant human and animal studies supporting the usefulness of end-tidal carbon dioxide, its optimal values during cardiopulmonary resuscitation remain controversial. In this review, the advantages and effectiveness of end-tidal carbon dioxide during cardiopulmonary resuscitation are discussed and specific target values are suggested based on the available literature. PMID- 26150003 TI - Forgotten Predictors of Prosthetic Valve Endocarditis. PMID- 26150004 TI - Twisted Leads: The Footprints of Malpositioned Electrocardiographic Leads. AB - BACKGROUND: Malposition of electrocardiograph (ECG) leads is poorly recognised even by cardiologists who report tracings. When ECG tracings are regularly performed by doctors, nurses or technicians, lead malposition is very uncommon particularly if the operator can also interpret the findings. However, a significant proportion of 12-lead ECG tracings are today performed in a doctor's surgery or by private pathology services, often in haste without sufficient attention to correct lead positioning. As a result, a variety of malposition combinations occur, which in turn may confuse the interpreter of the ECG tracing, leading to incorrect diagnoses. OBJECTIVES: To investigate various combinations of ECG lead malposition and determine if characteristic findings can be summarised into identifiable footprints. METHODS: In 10 normal subjects, 12-lead ECGs were performed with normal lead positioning as well as six limb lead malpositions and reversal of chest leads. RESULTS: In all subjects, there was consistency in the ECGs performed allowing the creation of five characteristic and easily identifiable footprints. CONCLUSIONS: A summary of the footprints of ECG lead malposition should be readily available for those who perform ECGs, those who interpret the tracings and those responsible for clinical care. PMID- 26150005 TI - Effects of the Pulmonary Hypertension Manual (PulHMan) on Awareness of Exercise in Patients with Pulmonary Hypertension. AB - BACKGROUND: Patient education is an important part of holistic care for patients with chronic diseases. With the success of the Heart Manual, it was felt there is a strong need to develop such a manual for those with pulmonary hypertension (PH) - the Pulmonary Hypertension Manual (PulHMan). This was developed through a qualitative methodology in order to ensure the needs of the patients were being met. The impact of the PulHMan on awareness about exercise-related benefits and PH are not known. Therefore the aim of this study was to assess the effects of the PulHMan on improving awareness among individuals with PH. METHODS: A repeat cross sectional study was carried out on 30 patients with PH to assess the effects of using the PulHMan on awareness of exercise-related benefits in PH. Awareness was assessed from a self-developed and validated questionnaire that included components of PH and exercise related components. RESULTS: Thirty patients with PH (mean right ventricular systolic pressure and six minute walk distance of 89.2+/-4.1mm Hg and 322.8+/-102m respectively) were included in the study. At baseline, it was seen that there was a low awareness regarding the benefits of exercise for PH. However, they were aware of the general health benefits of walking. After three months, it was seen that the PulHMan improved awareness on the benefits of exercising. Despite a low number willing to exercise (2/30) and participate in a home-based program (2/30), after using the PulHMan for three months, there was an improvement in those willing to exercise and participate in a home-based program (22/30 and 25/30 respectively). CONCLUSIONS: The PulHMan was seen to improve awareness regarding the exercise-related benefits among patients with PH. More studies are needed to determine if this change in awareness translates into a behavioural change for those with PH. PMID- 26150006 TI - Recurrent Balloon Rupture During Transcatheter Aortic Valve Replacement (TAVR) - Implication for Access Site Choice. PMID- 26150007 TI - Effects of amycenone on serum levels of tumor necrosis factor-alpha, interleukin 10, and depression-like behavior in mice after lipopolysaccharide administration. AB - Accumulating evidence suggests that inflammation plays a role in the pathophysiology of depression and that anti-inflammatory substances have antidepressant effects. Amycenone is obtained from extracts of the Yamabushitake (Hericium erinaceum). The purpose of this study is to examine whether amycenone shows anti-inflammatory and antidepressant effects in an inflammation-induced mouse model of depression. First, we examined the effects of amycenone on the serum levels of the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF alpha), and the anti-inflammatory cytokine, interleukin-10 (IL-10), after intraperitoneal administration of the bacterial endotoxin lipopolysaccharide (LPS). Oral administration of amycenone (50, 100, or 200mg/kg) markedly blocked an increase in the serum TNF-alpha levels after a single administration of LPS (0.5mg/kg). Furthermore, amycenone (200mg/kg) markedly increased the serum IL-10 levels by a single administration of LPS (0.5mg/kg). Next, we examined the effects of amycenone on depression-like behaviors in the tail-suspension test (TST) and forced swimming test (FST). Pretreatment with amycenone (200mg/kg) significantly attenuated LPS (0.5mg/kg)-induced increase of the immobility time by the TST and FST, indicating antidepressant effects of amycenone. In addition, oral administration of paroxetine (30mg/kg) showed anti-inflammatory and antidepressant effects in the same model. These findings suggest that amycenone has antidepressant effects in LPS-induced inflammation model of depression. Therefore, amycenone could represent a potential supplement to prevent inflammation-related depression. PMID- 26150009 TI - Countries should raise taxes on tobacco, says WHO. PMID- 26150008 TI - Ectopic shoot meristem generation in monocotyledonous rpk1 mutants is linked to SAM loss and altered seedling morphology. AB - BACKGROUND: In dicot Arabidopsis thaliana embryos two cotyledons develop largely autonomously from the shoot apical meristem (SAM). Recessive mutations in the Arabidopsis receptor-like kinase RPK1 lead to monocotyledonous seedlings, with low (10 %) penetrance due to complex functional redundancy. In strong rpk1 alleles, about 10 % of these (i. e. 1 % of all homozygotes) did not develop a SAM. We wondered whether RPK1 might also control SAM gene expression and SAM generation in addition to its known stochastic impact on cell division and PINFORMED1 (PIN1) polarity in the epidermis. RESULTS: SAM-less seedlings developed a simple morphology with a straight and continuous hypocotyl-cotyledon structure lacking a recognizable epicotyl. According to rpk1's auxin-related PIN1 defect, the seedlings displayed defects in the vascular tissue. Surprisingly, SAM less seedlings variably expressed essential SAM specific genes along the hypocotyl-cotyledon structure up into the cotyledon lamina. Few were even capable of developing an ectopic shoot meristem (eSM) on top of the cotyledon. CONCLUSIONS: The results highlight the developmental autonomy of the SAM vs. cotyledons and suggest that the primary rpk1 defect does not lie in the seedling's ability to express SAM genes or to develop a shoot meristem. Rather, rpk1's known defects in cell division and auxin homeostasis, by disturbed PIN1 polarity, impact on SAM and organ generation. In early embryo stages this failure generates a simplified monocotyledonous morphology. Once generated, this likely entails a loss of positional information that in turn affects the spatiotemporal development of the SAM. SAM-bearing and SAM-less monocotyledonous phenotypes show morphological similarities either to real monocots or to dicot species, which only develop one cotyledon. The specific cotyledon defect in rpk1 mutants thus sheds light upon the developmental implications of the transition from two cotyledons to one. PMID- 26150010 TI - Mapping the field of military nursing research 1990-2013: A bibliometric review. AB - BACKGROUND: Over the past 20 years, military forces worldwide have been engaged in a number of conflicts and humanitarian operations and the impact of this on the field of military nursing research is unknown. The aim of this bibliometric review was to investigate the research field of military nursing in the main databases with the purpose to describe trends in military nursing research since 1990. OBJECTIVES: To identify military nursing papers in the main databases and to describe the field of military nursing research for the period 1990-2013 in terms of research productivity, trends in topic focus, trends in authorship and country of publication. METHOD: Bibliometric review of published military nursing research papers was undertaken in March 2014 and data was extracted and coded and trends were analyzed using SPSSv21. RESULTS: In total 237 articles were included in the review. The majority of publications emanating from America (n=175, 73.8%) and the quantity of papers has increased significantly since the commencement of the second Gulf War in Iraq from 2003 onwards (n=156, 65.8%). This has been accompanied by a shift in topic focus from professional (n=16, 20.3%) and occupational issues (n=17, 21.5%) pre 2003, to clinical (n=48, 30.4%) and an increase in multidisciplinary research from 4% in 1990-94 to 29% in 2010-13. The mean citations were 10.6 (sd 17.0) and the mean references per paper post 2003 showed a marked increase from 23.5 to 25.4. CONCLUSION: The military nursing research field appears stronger than it has been in the past twenty years and has demonstrated increased transferability to other fields. To maintain this momentum and further develop the field of military nursing research, military forces worldwide need to devise focused nursing research strategies that involve international and multidisciplinary collaboration. PMID- 26150011 TI - Highly Sensitive and Stretchable Multidimensional Strain Sensor with Prestrained Anisotropic Metal Nanowire Percolation Networks. AB - To overcome the limitation of the conventional single axis-strain sensor, we demonstrate a multidimensional strain sensor composed of two layers of prestrained silver nanowire percolation network with decoupled and polarized electrical response in principal and perpendicular directional strain. The information on strain vector is successfully measured up to 35% maximum strain with large gauge factor (>20). The potential of the proposed sensor as a versatile wearable device has been further confirmed. PMID- 26150012 TI - An automated RNA-Seq analysis pipeline to identify and visualize differentially expressed genes and pathways in CHO cells. AB - Recent advances in RNA-Seq based comparative transcriptomics have opened up a unique opportunity to understand the mechanisms of different phenotypes in bioprocessing-related cell lines including Chinese hamster ovary (CHO) cells. However, simple and powerful tools are needed to translate large data sets into biologically relevant information that can be leveraged for genetic engineering and cell culture medium and process development. While tools exist to perform specific tasks associated with transcriptomics analysis, integrated end to end solutions that span the entire spectrum of raw data processing to visualization of gene expression changes on canonical pathways are rare. Additionally, these are not automated and require substantial user intervention. To address this gap, we have developed an automated RNA-Seq analysis pipeline in R which leverages the latest public domain statistical advances in transcriptomics data analysis. This pipeline reads RNA-Seq gene count data, identifies differentially expressed genes and differentially expressed pathways, and provides multiple intuitive visualizations as outputs. By using two publicly available CHO RNA-Seq datasets, we have demonstrated the utility of this pipeline. Subsequently, this pipeline was used to demonstrate transcriptomic similarity between laboratory- and pilot scale bioreactors, helping make a case for the suitability of the lab-scale bioreactor as a scaled-down model. Automated end to end RNA-Seq data analysis approaches such as the one presented in this study will shorten the time required from acquiring sequencing data to biological interpretation of the results and can help accelerate the adoption of RNA-Seq analysis and thus mechanism-driven approaches for cell line and bioprocess optimization. PMID- 26150013 TI - beta-Octamethoxy-Substituted 22pi and 26pi Stretched Porphycenes: Synthesis, Characterization, Photodynamics, and Nonlinear Optical Studies. AB - Three meso-expanded tetrapyrrolic aromatic macrocycles, including 22pi and 26pi acetylene-cumulene bridged stretched octamethoxyporphycenes and octamethoxy[22]porphyrin-(2.2.2.2), are reported, for the first time, by modification of previously reported synthetic methods. This strategy led to an enhancement in the overall yield of their corresponding octaethyl analogues. The methoxy-substituted expanded porphycenes display slightly blueshifted absorption relative to their ethyl analogues, along with very weak fluorescence, probably due to efficient intramolecular charge transfer (ICT). Additionally, the two photon absorption (TPA) cross sections of these macrocycles were evaluated; these are strongly related to core expansion of the porphyrin aromaticity through increased meso-bridging carbon atoms as well as conformational flexibility and substitution effects at the macrocyclic periphery. In particular, the octamethoxy stretched porphycenes display strong TPA compared with the octaethyl analogues due to the dominant ICT character of methoxy groups with a maximum TPA cross section of 830 GM at 1700 nm observed for 26pi-octamethoxyacetylene cumuleneporphycene. PMID- 26150015 TI - Ultrathin Two-Dimensional Pd-Based Nanorings as Catalysts for Hydrogenation with High Activity and Stability. AB - Despite a few reports on the synthesis of ultrathin 2D nanosheets made of noble metals, it still remains a tremendous challenge to generate their ultrathin hollowed nanostructures, which are of particular interest in highly active catalysis due to their unique structural features. Here, the synthesis of ultrathin 2D Pd nanorings is reported with a hollow interior by selective epitaxial growth of Pd atoms on the periphery of the as-preformed Pd nanosheets in combination with oxidative etching. This approach can be extended to fabricate Pd-based bimetallic ultrathin nanorings such as Pd-Pt. The Pd nanorings exhibit substantially enhanced activity toward the hydrogenation of p-nitrophenol, which is 2.2 and 33.4 times higher than that of the Pd nanosheets and commercial Pd black, respectively. Significantly, the Pd nanorings are highly stable with only less than 11% loss in activity compared to 45.7% loss of the Pd nanosheets and 72.2% loss of the Pd black after ten cycles. PMID- 26150014 TI - State disparities in colorectal cancer rates: Contributions of risk factors, screening, and survival differences. AB - BACKGROUND: Northeastern states of the United States have shown more progress in reducing colorectal cancer (CRC) incidence and mortality rates than Southern states, and this has resulted in considerable disparities. This study quantified how the disparities in CRC rates between Louisiana (a Southern state) and New Jersey (a Northeastern state) would be affected if differences in risk factors, screening, and stage-specific CRC relative survival between the states were eliminated. METHODS: This study used the Microsimulation Screening Analysis Colon microsimulation model to estimate age-adjusted CRC incidence and mortality rates in Louisiana from 1995 to 2009 under the assumption that 1) Louisiana had the same smoking and obesity prevalence observed in New Jersey, 2) Louisiana had the same CRC screening uptake observed in New Jersey, 3) Louisiana had the same stage specific CRC relative survival observed in New Jersey, or 4) all the preceding were true. RESULTS: In 2009, the observed CRC incidence and mortality rates in Louisiana were 141.4 cases and 61.9 deaths per 100,000 individuals, respectively. With the same risk factors and screening observed in New Jersey, the CRC incidence rate in Louisiana was reduced by 3.5% and 15.2%, respectively. New Jersey's risk factors, screening, and survival reduced the CRC mortality rate in Louisiana by 3.0%, 10.8%, and 17.4%, respectively. With all trends combined, the modeled rates per 100,000 individuals in Louisiana became lower than the observed rates in New Jersey for both incidence (116.4 vs 130.0) and mortality (44.7 vs 55.8). CONCLUSIONS: The disparities in CRC incidence and mortality rates between Louisiana and New Jersey could be eliminated if Louisiana could attain New Jersey's levels of risk factors, screening, and survival. Priority should be given to enabling Southern states to improve screening and survival rates. PMID- 26150016 TI - The structure of the Cyberlindnera jadinii genome and its relation to Candida utilis analyzed by the occurrence of single nucleotide polymorphisms. AB - The yeast Cyberlindnera jadinii is a close relative of Candida utilis that is being used in the food and feed industries. Here, we present the 12.7Mb genome sequence of C. jadinii strain CBS 1600 generated by next generation sequencing. The deduced draft genome sequence consists of seven large scaffolds analogous to the seven largest chromosomes of C. utilis. An automated annotation of the C. jadinii genome identified 6147 protein-coding sequences. The level of ploidy for both genomes was analyzed by calling single nucleotide polymorphisms (SNPs) and was verified measuring nuclear DNA contents by florescence activated cell sorting (FACS). Both analyses determined the level of ploidy to diploid for C. jadinii and to triploid for C. utilis. However, SNP calling for C. jadinii also identified scaffold regions that seem to be haploid, triploid or tetraploid. PMID- 26150017 TI - Complete genome sequence of Burkholderia pyrrocinia 2327(T), the first industrial bacterium which produced antifungal antibiotic pyrrolnitrin. AB - Burkholderia pyrrocinia 2327(T) (=DSM 10685(T), having an origin history as a strain Fujisawa Pharm 2327(T) from Fujisawa Pharmaceutical Co., Ltd.) is the first industrial bacterium for the isolation of antifungal antibiotic pyrrolnitrin. Herein, we present the first complete genome sequence of strain 2327(T), which consists of three circular chromosomes with one plasmid for the total 7,961,346bp sized genome with a GC content of 66.5%. This information will provide better understanding of molecular mechanisms in strain 2327(T), leading the insight of whole-cell system for the practical application of strain with the virtue of antibiotic capacity. PMID- 26150018 TI - Optimization of high solids fed-batch saccharification of sugarcane bagasse based on system viscosity changes. AB - Viscosity trends in alkali-pretreated sugarcane bagasse (SCB) slurries undergoing high solids fed-batch enzymatic hydrolysis were measured for a range of solids loading from 15% to 36%. Solids liquefaction times were related to system viscosity changes. The viscosity decreased quickly for low solids loading, and increased with increasing solids content. Fed-batch hydrolysis was initiated with 15% solids loading, and an additional 8%, 7% and 6% were successively added after the system viscosity decreased to stable values to achieve a final solids content of 36%. Two enzyme-adding modes with 8.5FPU/g solid were investigated. The batch mode with all enzyme being added at the beginning of the reaction produced the highest yields, with approximately 231.7g/L total sugars and 134.9g/L glucose being obtained after 96h with nearly 60% of the final glucan conversion rate. This finding indicates that under the right conditions, the fed-batch strategy might be a plausible way to produce high sugars under high solids. PMID- 26150019 TI - Do low step count goals inhibit walking behavior: a randomized controlled study. AB - OBJECTIVE: Confirmation and quantification of observed differences in goal directed walking behavior. DESIGN: Single-blind, split-half randomized trial. SETTING: Small rural university, Pennsylvania, United States. SUBJECTS: A total of 94 able-bodied subjects (self-selected volunteer students, faculty and staff of a small university) were randomly assigned walking goals, and 53 completed the study. INTERVENTIONS: Incentivized pedometer-monitored program requiring recording the step-count for 56-days into a custom-made website providing daily feedback. MAIN OUTCOME MEASURES: Steps logged per day. RESULTS: During the first half of the study, the 5000 and 10,000 step group logged significantly different steps 7500 and 9000, respectively (P > 0.05). During the second half of the study, the 5000 and 10,000 step groups logged 7000 and 8600 steps, respectively (significance P > 0.05). The group switched from 5000 to ->10,000 steps logged, 7900 steps for the first half and 9500 steps for the second half (significance P > 0.05). The group switched from 10,000 to 5000 steps logged 9700 steps for the first half and 9000 steps for the second half, which was significant (p > 0.05). CONCLUSIONS: Levels of walking behavior are influenced by the goals assigned. Subjects with high goals walk more than those with low goals, even if they do not meet the assigned goal. Reducing goals from a high to low level can reduce walking behavior. PMID- 26150020 TI - The efficacy of Botulinum Toxin A for limb spasticity on improving activity restriction and quality of life: a systematic review and meta-analysis using the GRADE approach. AB - OBJECTIVES: A systematic review and meta analysis using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. The aim was to evaluate the efficacy of Botulinum Toxin type A for limb spasticity on improving activity restriction and quality of life outcomes. DATA SOURCES: Pubmed, Cinahl, Amed, Embase and Cochrane databases. English Language. Search to January 2015. REVIEW METHODS: All randomized, placebo controlled trials on adults with active function or quality of life measures for the arm and leg relating to spasticity of any origin and treated with a single dose of Botulinum Toxin A. Evidence quality was assessed by GRADE. RESULTS: Twenty-five studies were reviewed. Meta analysis was carried out on six upper limb and six lower limb studies. Evidence quality for the upper limb was low/very low. A significant result for Botulinum Toxin A was found at four to twelve weeks for the upper limb for active function (SMD 0.32 CI 0.01, 0.62, P=0.04) These effects were maintained for up to six months for Active Research Arm Test (ARAT) only (MD 1.87 CI 0.53, 3.21, P=0.006).Evidence quality was very low for the lower limb. No significant effect was found. Meta analysis was not possible for quality of life measures. CONCLUSION: Botulinum Toxin A may improve active outcomes in the upper limb but further evidence is needed. No conclusion can be drawn about the effect on active outcomes for the lower limb or for quality of life measures in either limb. PMID- 26150021 TI - Low-frequency electroacupuncture suppresses focal epilepsy and improves epilepsy induced sleep disruptions. AB - BACKGROUND: The positive effects of acupuncture at Feng-Chi acupoints on treating epilepsy and insomnia have been well-documented in ancient Chinese literature. However, there is a lack of scientific evidence to elucidate the underlying mechanisms behind these effects. Our previous study demonstrated that high frequency (100 Hz) electroacupuncture (EA) at Feng-Chi acupoints deteriorates both pilocarpine-induced focal epilepsy and sleep disruptions. This study investigated the effects of low-frequency (10 Hz) EA on epileptic activities and epilepsy-induced sleep disruptions. RESULTS: In rats, the Feng-Chi acupoint is located 3 mm away from the center of a line between the two ears. Rats received 30 min of 10 Hz EA stimuli per day before each day's dark period for three consecutive days. Our results indicated that administration of pilocarpine into the left CeA at the beginning of the dark period induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep during the consequent light period. Low-frequency (10 Hz) EA at Feng-Chi acupoints suppressed pilocarpine-induced epileptiform EEGs, and this effect was in turn blocked by naloxone (a broad-spectrum opioid receptor antagonist), but not by naloxonazine (a MU-receptor antagonist), naltrindole (a delta-receptor antagonist) and nor-binaltorphimine (a kappa-receptor antagonist). Ten Hz EA enhanced NREM sleep during the dark period, and this enhancement was blocked by all of the opioid receptor antagonists. On the other hand, 10 Hz EA reversed pilocarpine-induced NREM suppression during the light period, and the EA's effect on the sleep disruption was only blocked by naloxonazine. CONCLUSIONS: These results indicate that low-frequency EA stimulation of Feng-Chi acupoints is beneficial in improving epilepsy and epilepsy-induced sleep disruptions, and that opioid receptors in the CeA mediate EA's therapeutic effects. PMID- 26150022 TI - Impact of Prophylactic Levofloxacin on Rates of Bloodstream Infection and Fever in Neutropenic Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation. AB - Few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (HSCT). At our center, levofloxacin prophylaxis was initiated in June 2006 in patients with myeloma who were undergoing autologous HSCT. We compared the incidence of bloodstream infection (BSI) and fever and neutropenia (FN) within 30 days of transplantation before (January 2003 to May 2006) and after (June 2006 to April 2010) the initiation of levofloxacin prophylaxis in patients undergoing autologous HSCT for myeloma. We also compared rates of BSI and FN during the same time periods in autologous HSCT recipients with lymphoma who did not receive antibacterial prophylaxis during either time period. After the initiation of levofloxacin prophylaxis, the BSI rate decreased from 41.2% (49 of 119) to 14.7% (23 of 156) and the rate of FN decreased from 91.6% to 60.9% in patients with myeloma (P < .001, for each). In contrast, rates of BSI (43.1% versus 47.3%; P = .50) and FN (98.8% versus 97.1%; P = .63) did not change in patients with lymphoma. Levofloxacin prophylaxis was independently associated with decreased odds of BSI (odds ratio, .27; 95% confidence interval, .14 to .51; P < .001) and FN (odds ratio, .18; 95% confidence interval, .09 to .36; P < .001) in multivariate analysis. Patients with myeloma had a nonsignificant increase in the risk of BSI due to levofloxacin-resistant Enterobacteriaceae (5% versus 1%, P = .08) and Clostridium difficile infection (7% versus 3%, P = .12) after the initiation of levofloxacin prophylaxis but did not have higher rates of BSI due to other resistant bacteria. Levofloxacin prophylaxis is associated with decreased risk of BSI and FN in patients with myeloma undergoing autologous HSCT. PMID- 26150023 TI - Histologic Features of Intestinal Thrombotic Microangiopathy in Pediatric and Young Adult Patients after Hematopoietic Stem Cell Transplantation. AB - High-risk transplantation-associated thrombotic microangiopathy (TMA) can present with multisystem involvement and is associated with a poor outcome after hematopoietic stem cell transplantation (HSCT), with < 20% 1-year survival. TMA may involve the intestinal vasculature and can present with bleeding and ischemic colitis. There are no established pathologic criteria for the diagnosis of intestinal TMA (iTMA). The goal of our study was to identify histologic features of iTMA and describe associated clinical features. We evaluated endoscopic samples from 50 consecutive HSCT patients for 8 histopathologic signs of iTMA and compared findings in 3 clinical groups based on the presence or absence of systemic high-risk TMA (hrTMA) and the presence or absence of clinically staged intestinal graft-versus-host disease (iGVHD): TMA/iGVHD, no TMA/iGVHD, and no TMA/no iGVHD. Thirty percent of the study subjects had a clinical diagnosis of systemic hrTMA. On histology, loss of glands, intraluminal schistocytes, intraluminal fibrin, intraluminal microthrombi, endothelial cell separation, and total denudation of mucosa were significantly more common in the hrTMA group (P < .05). Intravascular thrombi were seen exclusively in patients with hrTMA. Mucosal hemorrhages and endothelial cell swelling were more common in hrTMA patients but this difference did not reach statistical significance. Patients with hrTMA were more likely to experience significant abdominal pain and gastrointestinal bleeding requiring multiple blood transfusions (P < .05). Our study shows that HSCT patients with systemic hrTMA can have significant bowel vascular injury that can be identified using defined histologic criteria. Recognition of these histologic signs in post-transplantation patients with significant gastrointestinal symptoms may guide clinical decisions. PMID- 26150025 TI - A limited TB intervention in remote Taiwan: observations 10 years later. AB - BACKGROUND: A brief but comprehensive TB elimination program began in a remote region of Taiwan in 1997 involving five contiguous villages (n=2308). METHODS: An aggressive intervention included tuberculin skin testing and treatment of latent TB infection. Normal program data was collected and later analyzed forming the basis of an operational research study. RESULTS: An initial 31% reduction in active TB cases (81 to 56 over 4 years) (p=0.033) was observed and persisted until the end of the 10-year follow-up period despite no further intervention. In the control population, no sustained reduction of TB was noted for the same period. CONCLUSIONS: Although encouraging, a more robust study is needed to reasonably attribute the persistence of this significantly lower TB rate to this brief intensive intervention. PMID- 26150024 TI - Short Communication: Comparative Evaluation of Coformulated Injectable Combination Antiretroviral Therapy Regimens in Simian Immunodeficiency Virus Infected Rhesus Macaques. AB - The use of nonhuman primate (NHP) models to study persistent residual virus and viral eradication strategies in combination antiretroviral therapy (cART)-treated individuals requires regimens that effectively suppress SIV replication to clinically relevant levels in macaques. We developed and evaluated two novel cART regimens in SIVmac239-infected rhesus macaques: (1) a "triple regimen" containing the nucleo(s/t)ide reverse transcriptase inhibitors emtricitabine (FTC) and tenofovir disoproxil fumarate [TDF, prodrug of tenofovir (TFV, PMPA)] with the integrase strand transfer inhibitor dolutegravir (DTG) (n = 3), or (2) a "quad regimen" containing the same three drugs plus the protease inhibitor darunavir (DRV) (n = 3), with each regimen coformulated for convenient administration by a single daily subcutaneous injection. Plasma drug concentrations were consistent across animals within the triple and quad regimen-treated groups, although DTG levels were lower in the quad regimen animals. Time to achieve plasma viral loads stably <30 viral RNA copies/ml ranged from 12 to 20 weeks of treatment between animals, and viral loads <30 viral RNA copies/ml plasma were maintained through 40 weeks of follow-up on cART. Notably, although we show virologic suppression and development of viral resistance in a separate cohort of SIV-infected animals treated with oral DRV monotherapy, the addition of DRV in the quad regimen did not confer an apparent virologic benefit during early treatment, hence the quad regimen-treated animals were switched to the triple regimen after 4 weeks. This coformulated triple cART regimen can be safely, conveniently, and sustainably administered to durably suppress SIV replication to clinically relevant levels in rhesus macaques. PMID- 26150026 TI - Designing ancillary ligands for heteroleptic/homoleptic zinc complex formation: synthesis, structures and application in ROP of lactides. AB - Synthesis and characterization of a series of new amino-phenol/naphthol ligands (L(1,2)-H) have been developed and their respective zinc complexes ( 1 and 2-Zn ) have been synthesized. The molecular structures of L(1)-H and 1, 2-Zn were explored in detail by NMR, single-crystal X-ray studies and DFT calculations, which confirmed the existence of complexes as stabile dimers both in a solution and in the solid state. All complexes mediate the ring-opening polymerization (ROP) of lactide highly efficiently, at room temperature, in a controlled fashion. The influence of the architecture of the ligand on the desired homo/heteroleptic complex formation, as well as the relationship between the initiator design and the catalytic activity have been investigated. PMID- 26150027 TI - Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group. AB - OBJECTIVE: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. MATERIALS AND METHODS: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. RESULTS: Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. CONCLUSIONS: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content >= 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. CHILDREN: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved. PMID- 26150028 TI - Efficacy and safety of second-line agents for treatment of metastatic castration resistant prostate cancer progressing after docetaxel. A systematic review and meta-analysis. AB - OBJECTIVE: We performed a systematic review of the literature to assess the efficacy and the safety of second-line agents targeting metastatic castration resistant prostate cancer (mCRPC) that has progressed after docetaxel. Pooled analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel). MATERIALS AND METHODS: We included phase III randomized controlled trials that enrolled patients with mCRPC progressing during or after first-line docetaxel treatment. Trials were identified by electronic database searching. The primary outcome of the review was overall survival. Secondary outcomes were radiographic progression-free survival (rPFS) and severe adverse effects (grade 3 or higher). RESULTS: Ten articles met the inclusion criteria for the review. These articles reported the results of five clinical trials, enrolling in total 5047 patients. The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. Compared to control cohorts (active drug-treated or placebo-treated), the significant overall survival advantages achieved were 4.8 months for enzalutamide (hazard ratio for death vs. placebo: 0.63; 95% CI 0.53 to 0.75, P < 0.0001), 4.6 months for abiraterone (hazard ratio for death vs. placebo: 0.66, 95% CI 0.58 to 0.75, P < 0.0001) and 2.4 months for cabazitaxel (hazard ratio for death vs. mitoxantrone-prednisone: 0.70, 95% CI 0.59 to 0.83, p < 0.0001). Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P < 0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P < 0.00001). Androgen synthesis inhibitors induced significant increases in risk ratios for adverse effects linked to elevated mineralocorticoid secretion, compared to placebo (risk ratio for hypokalemia: 5.75, 95% CI 2.08 to 15.90; P = 0.0008; risk-ratio for hypertension: 2.29, 95% CI 1.02 to 5.17; P = 0.05). CONCLUSIONS: In docetaxel-pretreated patients enzalutamide, abiraterone prednisone and cabazitaxel-prednisone can improve overall survival of patients, compared to placebo or to best of care at the time of study (mitoxantrone prednisone). Agents targeting the androgen axis (enzalutamide, abiraterone, orteronel) significantly prolonged rPFS, compared to placebo. Further investigation is warranted to evaluate the benefit of combination or sequential administration of these agents. Large-scale studies are also necessary to evaluate the impact of relevant toxic effects observed in a limited number of patients (e.g., enzalutamide-induced seizures, orteronel-induced pancreatitis, and others). PMID- 26150029 TI - What is the correct staging and treatment strategy for locally advanced prostate cancer extending to the bladder? AB - In locally advanced prostate cancer with bladder invasion, frequently encountered problems such as bleeding, urinary retention, hydronephrosis, and pain create distress for the patients. Therefore patients' quality of life is disrupted and duration of hospitalization is prolonged. Relevant literature about accurate staging and treatment of locally advanced prostate cancer with bladder invasion was investigated. Locally advanced prostate cancer can present as a large-volume aggressive tumor extending beyond boundaries of prostate gland, and involving neighboring structures which can be involved as recurrence(s) following initial local therapy. Survival times of these patients can range between 5 and 8 years. Their common characteristics are adverse and severe local symptoms unfavorably affecting quality of life Control of local symptoms and their effective palliation are independent clinical targets influencing survival outcomes of these patients. The treatment outcomes of locally advanced prostate cancer into the bladder are currently debatable. Although in the current TNM classification, it is defined in T4a, we think that this may be categorized as a subgroup of T3 and thus encourage surgeons for the indication of radical surgeries (radical prostatectomy, radical cystoprostatectomy) in selected patient populations after discussing issues concerning consequences of the treatment alternatives, and expectations with the patients. Cystoprostatectomy followed by immediate androgen deprivation therapy may be a feasible option for selected patients with previously untreated prostate cancer involving the bladder neck because of excellent local control and long term survival. PMID- 26150030 TI - Influence of antiplatelet-anticoagulant drugs on the need of blood components transfusion after vesical transurethral resection. AB - AIMS: The effect of the antithrombotic preventive therapy on haemorrhage keeps uncertain. We investigate the influence of the antiplatelet and anticoagulant drugs (AP/AC drugs) on the transfusion requirement after vesical transurethral resection (VTUR). We also describe the epidemiology of the blood components transfusion in our department. MATERIALS AND METHODS: Retrospective observational study of a series of patients needing blood transfusion at the Urology Department between June 2010 and June 2013. Selection of 100 consecutive patients who were transfused after VTUR due to bladder transitional cell carcinoma (BTCC) (group A = GA). CONTROL GROUP: 100 consecutive patients who underwent VTUR due to BTCC and were not transfused (group B = GB). Transfusion criteria: Haemoglobin < 8 g/dl + anaemia symptoms. Age, gender, associated AP/AC treatment, secondary diagnoses, toxics, tumour stage and grade were analysed. RESULTS: 212 patients required transfusion of a blood component. 169 were men (79%) and 43 women (21%). Median age 77.59 years (SD 9.42, range 50-92). Secondary diagnoses: Diabetes Mellitus 64%, high blood pressure 77%, dyslipidemia 52%. 60% of patients were previously treated with AP/AC drugs. Average Haemoglobin pre-transfusion values: 7.4 g/dl (DE +/- 0.7). Average Haemoglobin post-transfusion values: 8.9 g/Dl (DE +/- 0.72). Most frequent transfusion indications were bladder cancer (37%), kidney cancer (11%), prostate cancer (8%), benign prostatic hyperplasia (BHP) (8%), other urological diagnoses (36%). Intraoperative transfusions indicated by the anaesthesiologist: kidney cancer (33%), BPH (28%). Patients who underwent VTUR due to BTCC were older in GA (77.59 years SD 9.42) than in GB (68.98 years SD 11.78) (p = 0.0001). Similar gender distribution (15 women in GA and 24 in GB). Less patients were asked to keep their treatment with ASA 100mg (AcetylSalicylicAcid) in GA (25.64%) than in GB (50%) (p = 0.0330). More aggressive tumour grade in GA (p = 0.0003) and higher stage in GA (p = 0.0018) regardless of concomitant treatment with AP/AC drugs. CONCLUSIONS: The pathologies which most needed blood components' transfusions in the Urology Department were (in order of frequency): bladder cancer, kidney cancer, prostate cancer, prostate adenoma. ASA100mg did not influence the transfusion's requirements in VTUR due to BTCC. Tumour stage and higher grade have a greater influence in transfusion's requirements than concomitant AP/AC treatment. The heterogeneity of AP/AC protocols does not allow to establish the benefit of stopping those drugs before surgery in terms of avoiding blood transfusions when performing a VTUR. PMID- 26150031 TI - Safety of greenlight photoselective vaporisation of prostate in lower urinary tract symptoms due to benign prostatic hyperplasia in patients using anticoagulants due to cardiovascular comorbidities. AB - Lasers have been used in the management of benign prostatic hyperplasia for the last two decades. To be comparable, they should reduce or avoid the immediate and long-term complications of transurethral resection of the prostate (TURP) or open prostatectomy (OP), especially bleeding and need for blood transfusion. Although Holmium laser treatment of the prostate was compared frequently in terms of cardiovascular safety with TURP or OP, photoselective vaporisation of the prostate (PVP) was not largely evaluated. In this article we analyzed the current literature to see if there is convincing data to support the observation of some authors that use of PVP is associated with increased safety in patients on anticoagulants with cardiovascular comorbidities. With this purpose a Medline search between January 2004 to March 2013 was performed using evidence obtained from randomised trials, well-designed controlled studies without randomisation, individual cohort studies, individual case control studies and case reports RESULTS: In the last 10 years, several case-control and cohort studies have demonstrated the efficacy of PVP as well as its safety in patients with cardiovascular comorbidities using anticoagulants. The results confirmed the overall lower perioperative and postoperative morbidity of PVP, whereas the efficacy was comparable to TURP in the short term, despite a higher reoperation rate. CONCLUSION: Although it is still developing, PVP with KTP or LBO seems to be a promising alternative to both TURP and OP in terms of cardiovascular safety and in patients using anticoagulants. PMID- 26150032 TI - Our percutaneous nephrolitotomy experience in patients with horseshoe kidney. AB - OBJECTIVES: Horseshoe kidney is the most common renal congenital fusion anomaly. Kidney stone formation is more common in horseshoe kidneys and some of them requires surgical procedure. So we want to evaluate the results of PNL in patients with horseshoe kidney anomaly. MATERIAL AND METHOD: Between January 2009 January 2014 PNL operation was performed in 6 patients with horseshoe kidney anomaly in our clinic. Success of surgery and postoperative/peroperative complications were evaluated retrospectively. RESULTS: No severe complications occurred in any patient caused by surgery. Three patients became stonefree. One patient had less than 4 mm. residual stone, two patients had more than 4 mm. residual stone. CONCLUSION: PNL is safe surgical method and it can be performed successfully in patients with horseshoe kidney anomaly. PMID- 26150033 TI - Evaluation of Tl-201 SPECT imaging findings in prostate cancer. AB - OBJECTIVES: To compare with histopathological findings the findings of prostate cancer imaging by SPECT method using Tl-201 as a tumor seeking agent. METHODS: The study comprised 59 patients (age range 51-79 years, mean age 65.3 +/- 6.8 years) who were planned to have transrectal ultrasonography (TRUS)-guided biopsies due to suspicion of prostate cancer between April 2011 and September 2011. Early planar, late planar and SPECT images were obtained for all patients. Scintigraphic evaluation was made in relation to uptake presence and patterns in the visual assessment and to Tumor/Background (T/Bg) ratios for both planar and SPECT images in the quantitative assessment. Histopathological findings were compatible with benign etiology in 36 (61%) patients and malign etiology in 23 (39%) patients. Additionally, comparisons were made to evaluate the relationships between uptake patterns,total PSA values and Gleason scores. RESULTS: A statistically significant difference was found between the benign and malignant groups in terms of uptake in planar and SPECT images and T/Bg ratios and PSA values. No statistically significant difference was found between uptake patterns of planar and SPECT images and Gleason scores in the malignant group. CONCLUSIONS: SPECT images were superior to planar images in the comparative assessment. Tl-201 SPECT imaging can provide an additional contribution to clinical practice in the diagnosis of prostate cancer and it can be used in selected patients. PMID- 26150034 TI - Different presentation types of primary Brucella epididimo-orchitis. AB - Brucellosis is a zoonotic disease that involved genitourinary system in 2-20% and most commonly cause single sided epididymo-orchitis. In our country Brucella is an endemic disease and causes serious and different diagnosis of acute scrotum and epididymo-orchitis. In this paper six cases of epididymo-orchitis cases which were resistant to classical treatment were discussed according to clinical and laboratory findings. We describe different types of presentation of Brucella epididymo-orchitis with diagnosis and treatment modalities. PMID- 26150035 TI - Lower urinary tract symptoms associated with neurological conditions: Observations on a clinical sample of outpatients neurorehabilitation service. AB - OBJECTIVES: The overall aims of this study were to investigate the lower urinary tract symptoms (LUTS) associated with neurological conditions and their prevalence and impact on a clinical sample of outpatients of a neurorehabilitation service. MATERIALS AND METHODS: We reviewed the files of 132 patients treated in our neurorehabilitation service from December 2012 to December 2013. Patients were divided into several subgroups based on the neurological diagnosis: Multiple Sclerosis (MS), other demyelinating diseases, Peripheral Neuropathy, neurovascular disorders (ND), neoplastic disease, traumatic brain injury (TBI), Parkinson and Parkinsonism, spinal cord injuries (SCI). Urinary status was based on medical evaluations of history of LUTS, type, degree, onset and duration of symptoms. We tried to analyze prevalence, kind of disorder, timing of presentation (if before or after the neurological onset) and eventual persistence of urological disorders (in the main group and in all subgroups). RESULTS: At the time of admission to our rehabilitation service, LUTS were observed in 14 out of 132 cases (11%). A high proportion of these outpatients (64.2%) presented bothersome urinary symptoms such as incontinence, frequency and urgency (storage LUTS). The most frequent symptom was urinary urge incontinence (42.8%). This symptom was found to be prevalent in the multiple sclerosis and neurovascular disorders. In 93% the urinary symptoms arose as a result of neurologic conditions and 78.5% did not present a complete recovery of urological symptoms in spite of improved self-reported functional activity limitations. None of these patients performed urological rehabilitation. CONCLUSIONS: Neurological disorders are a significant issue in rehabilitation services and it can lead to lower tract dysfunction, which causes LUTS. Storage symptoms are more common, especially urge incontinence. Current literature reports that a further optimization of the rehabilitation potential of neurologically ill patients is possible through an implementation of urological basic measures into the neurological treatment routine. PMID- 26150036 TI - Use of transvaginal ultrasound in females with primary bladder neck obstruction. A preliminary study. AB - INTRODUCTION AND AIM: The video-urodynamics study is the principal exam to establish a possible primary bladder neck obstruction (PBNO) condition. While trans-rectal ultrasonography plays an important role in the evaluation of the low urinary tract symptoms (LUTS) and the severity of bladder outlet obstruction (BOO) in men, the use of the transvaginal ultrasound (TVUS) in women with symptoms suggesting BOO remains unclear. We tried to check the utility of the TVUS in women with PBNO condition. MATERIAL AND METHODS: We selected female patients which presented BOO without pelvic organ prolapse (POP). According to the data of the video-urodynamic exam we selected the patients with the suspicion of PBNO. A TVUS in basal and during micturition was performed before and after surgery. RESULTS: TVUS showed a closed bladder neck bladder in basal condition and during micturition similarly to the fluoroscopic image during video urodynamics. The mean distance from bladder neck to the vaginal mucosa resulted 1.3 cm in this patients. CONCLUSIONS: TVUS results worthy in the evaluation of patients with PBNO before and after surgery. PMID- 26150037 TI - Internal urethrotomy versus plasmakinetic energy for surgical treatment of urethral stricture. AB - PURPOSE: we aimed to compare the longterm outcome of surgical treatment of urethral stricture with the internal urethrotomy and plasmakinetic energy. MATERIAL AND METHODS: 60 patients, who have been operated due to urethral stricture were enrolled in our clinic. None of the patients had a medical history of urethral stricture. The urethral strictures were diagnosed by clinical history, uroflowmetry, ultrasonography and urethrography. The patients were divided two groups. Group 1 consisted of 30 patients treated with plasmakinetic urethrotomy and group 2 comprised 30 men treated with cold knife urethrotomy. RESULTS: There were no statistically significant differences between two groups in terms of patient age, maximum flow rate (Qmax) and quality of life score (Qol) value. A statistical difference between the two groups was observed when we compared the 3rd-month uroflowmetry results. Group 1 patients had a mean postoperative Qmax value of 16,1 +/- 2,3 ml/s, whereas group 2 had a mean postoperative Qmax value of 15,1 +/- 2,2 ml/s (p < 0.05). In the cold knife group, 3 of 11 (27,7%) recurrences appeared within the first 3 months, whereas in the plasmakinetic group zero recurrences appeared within the first 3 months in our study. The urethral stricture recurrence rate up to the 12 month period was statistically significant for group 1 (n = 7, 23%) compared with group 2 (n = 11, 37%) (p < 0.05). CONCLUSION: We believe that plasmakinetic surgery is better method than the cold knife technique for the treatment of urethral stricture. PMID- 26150038 TI - Correcting and sharing our complications. Misplacement of pigtail catheter, during a Robot Assisted Pyeloplasty. Clinical findings, diagnosis, possible causes and endoscopic treatment. AB - OBJECTIVE: Robotic assisted pyeloplasty (RAP) is rapidly adopted by surgeons around the world. We present a unique complication of the technique, consisting of pigtail misplacement, which was endoscopically resolved. We discuss the clinical findings, differential diagnosis and principles of endoscopic treatment. MATERIALS AND METHODS: A 41 years old female patients underwent transperitoneal right side RAP with the Hynes-Anderson technique for ureteropelvic junction obstruction. Pigtail was placed intraoperatively in an antegrade fashion. Post operative course appeared normal but Kidney-Ureterer-Bladder(KUB) X-ray, revealed a misplaced pigtail. Patient underwent a semirigid ureterorenoscopy demonstrating that the pigtail was exiting the collecting system in the rear line of suturing between continuous sutures. Pigtail was retrieved with a stone retrieval forceps with short upward motions in the renal pelvis under fluoroscopy and then removed from patient, in order to avoid stressing the anastomosis. No leakage was noted in fluoroscopy, a pigtail was correctly placed and patient recovery was uneventful. RESULTS: Retrograde pyelography was the key to accurate diagnosis and endoscopic treatment, because the exact point of exit and anastomosis integrity were established. Retrieval of the pigtail was the most challenging part. Lack of proper visualization and mobilization of the rear part of the anastomosis during surgery, combined with lack of tactile feedback, because of robotic instrumentation, were of critical importance in the manifestation of such a mishap. Endoscopy facilitated case resolve, but proper handling is required to protect the anastomosis. CONCLUSIONS: The introduction of novel techniques can carry the burden of novel complications. A surgeon must always keep in mind the complications inherent to the technique and at the same time the limitations of the equipment used, especially the lack of tactile feedback in robotic instrumentation. PMID- 26150039 TI - Recurrence of sigmoid colon carcinoma in the retained urethra after cystectomy: A case report and review of the literature. AB - Urethral recurrence arising from a primary colorectal adenocarcinoma is rare. Here, we report a case of urethral recurrence of sigmoid colon cancer, which developed after cysto-prostato-sigmoidectomy for sigmoid colon cancer invading the bladder. The patient underwent urethrectomy successfully and is currently tumor-free. Surgeons who follow patients with colorectal cancer invading the bladder should be aware of this case. The early detection of recurrence improves the chances for disease-free survival. PMID- 26150041 TI - Penile plaque as predictor of an advanced anorectal carcinoma: A case report. AB - The secondary involvement of the penis by tumors from others organs is a rare event representing only 0.8% of overall metastasis in the genitourinary tract. The most frequent clinical findings is priapism, but occasionally, solitary metastases to the penile skin, mucosa of the glans, corpus spongiosum or lesions of the albuginea mimicking an induratio penis have been reported. We report a case of penile plaque predicting the relapse of an anorectal carcinoma. The precise etiology of this particular manifestation is not well understood and the prognosis is poor. There are no individual treatments with curative intent. PMID- 26150040 TI - Giant renal artery aneurysm: A case report. AB - A case of a 12 cm giant renal artery aneurysm (RAA) in an 59-year-old woman is reported. The patient was referred to our hospital for flank pain and spot hematuria. Ultrasonography (US) revealed some wide lacunar areas in her right kidney and a thin cortex. Three-dimensional computed tomography (3D-CT) revealed a giant right renal arteriovenous malformation (AVM). AngioCT scan showed a pervious right renal artery. The cavities of the right kidney were dilated and the parenchyma was markedly reduced. Two months later the patient underwent an open resection of the aneurysm and a right nephrectomy. She had an uneventful recovery and a healthy status (last follow-up: 9 month). In this particular case, a safe approach is the transabdominal approach since the aneurysm was very large, friable, and located on the right side. This report confirms the opportunity of a planned nephrectomy once there is adequate renal reserve in the opposite kidney using a midline approach. PMID- 26150042 TI - Patch bulging after plaque incision and grafting procedure for Peyronie's disease. Surgical repair with a collagen fleece. AB - The incision/excision and grafting techniques (PIG) for surgical therapy of Peyronie's disease (PD) have gained popularity in recent years. Several different graft materials have been used but the ideal graft has yet to be established. The use of grafting materials could cause complications. In the daily clinical practice it will always be more frequent to manage complications arising from their use. We present herein the case of a patch bulging repaired with a ready-to use collagen fleece (Tachosil(r), Takeda, Linz, Austria, Europe) in a 61 years old man subjected to intervention of geometric corporoplasty with Paulo Egydio technique using an acellular collagen material (Xenform(r) patch, Boston Scientific, Natick, MA, USA) as graft. We also discuss the possible implications of PIG procedure. PMID- 26150043 TI - A rare complication after renal transplantation: Forgotten stent. AB - In renal transplantation surgery, double J stents (DJS) are often used to reduce complications, protect the anastomosis between ureter and bladder, provide drainage in ureteral obstructions and enhance healing if there is an ureter injury. Urinary tract infections, hematuria and irritative voiding symptoms are the early complications of DJS. Migration, fragmentation, encrustation and rarely sepsis are among the late complications of DJS. In this report we describe a renal transplantation case whose DJS stent was forgotten because the patient did not attend the regular follow-up and noticed 5 years after surgery. PMID- 26150044 TI - Extraintestinal gastrointestinal stromal tumor of undetermined origin: Is the mass resection a wrong approach? A case report and review of the literature. AB - Gastrointestinal stromal tumor (GIST) was first defined by Mazur et al. in 1983. GIST is evaluated among tumoral lesions that can be acquired or congenital. Those not associated with gastrointestinal system are termed as extragastrointestinal stromal tumor (EGIST). EGISTs can develop on intraperitoneal spaces as omentum, mesenterium and gallbladder and they can occur on retroperitoneum, extraperitoneal (prostate) and intrapelvic organs. Herein, we present a case with EGIST in a 65-year-old male patient located in intrapelvic and retroprostatic area which had no connection with gastrointestinal system as assessed by radiological methods and we discuss its treatment. We reviewed the literature and observed that ours is the first case report on a patient in which the mass was only extirpated rather than performing radical surgery. He is still at the 2. year of his follow-up period without any disease recurrence. PMID- 26150045 TI - Lower pole renal cut injury due to the iliac wing fracture: A rare case report. AB - The most frequent causes of blunt genitourinary injuries are falls from heights, motor vehicle accidents and sports injuries. Firearm injuries and penetrating stab wounds are also frequently encountered. Skeletal system traumas in the vicinity of the urogenital system can cause urological organ injuries. Though rarely, renal traumas can be dependent on the kinetic energy of the trauma and the retroperitoneal movement capacity of the kidneys and cannot be explained with the proximity of the kidney to the skeletal system. In cases with high-energy decelerations, renal pedicle and ureteropelvic junction traumas are more frequently observed. Herein, we presented a grade 3 left kidney lower pole injury developed secondary to A2 type pelvic fracture following a high energy deceleration trauma. It should not be forgotten that especially in this type of fractures, injuries of the lower renal pole can occur. PMID- 26150046 TI - Rare case of intra-testicular adenomatoid tumour. PMID- 26150047 TI - Evolutionary consequences of climate-induced range shifts in insects. AB - Range shifts can rapidly create new areas of geographic overlap between formerly allopatric taxa and evidence is accumulating that this can affect species persistence. We review the emerging literature on the short- and long-term consequences of these geographic range shifts. Specifically, we focus on the evolutionary consequences of novel species interactions in newly created sympatric areas by describing the potential (i) short-term processes acting on reproductive barriers between species and (ii) long-term consequences of range shifts on the stability of hybrid zones, introgression and ultimately speciation and extinction rates. Subsequently, we (iii) review the empirical literature on insects to evaluate which processes have been studied, and (iv) outline some areas that deserve increased attention in the future, namely the genomics of hybridisation and introgression, our ability to forecast range shifts and the impending threat from insect vectors and pests on biodiversity, human health and crop production. Our review shows that species interactions in de novo sympatric areas can be manifold, sometimes increasing and sometimes decreasing species diversity. A key issue that emerges is that climate-induced hybridisations in insects are much more widespread than anticipated and that rising temperatures and increased anthropogenic disturbances are accelerating the process of species mixing. The existing evidence only shows the tip of the iceberg and we are likely to see many more cases of species mixing following range shifts in the near future. PMID- 26150048 TI - Dysphagia Caused by Chronic Laryngeal Edema. AB - A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office. PMID- 26150049 TI - Transdermal delivery of therapeutic agents using dendrimers (US20140018435A1): a patent evaluation. AB - Transdermal drug delivery offers a number of advantages over systematic administrations such as oral administration and intravenous injection. However, most therapeutic agents are limited in transdermal delivery due to the presence of a stratum corneum barrier. A number of chemical penetration enhancers were used to facilitate the penetration of drugs with poor skin permeability across the barrier, but these enhancers are usually associated with safety concerns such as skin irritation and immune response. The current patent application by Hong et al. provides the potential use of surface-engineered dendrimers for transdermal delivery of therapeutic agents. It systemically demonstrates the effect of dendrimer generation, surface chemistry and hydrophobicity on the skin permeability of dendrimers. The most efficient dendrimer shows nearly 30% skin permeation when its surface was conjugated with endoxifen, a drug widely used for the treatment of breast cancers. The described technique provides an efficient and safe method for the delivery of therapeutic agents, especially chemopreventive compounds and anticancer drugs. PMID- 26150050 TI - Evaluation of 6beta-Hydroxycortisol and 6beta-Hydroxycortisone as Biomarkers for Cytochrome P450 3A Activity: Insight into Their Predictive Value for Estimating Oral Immunosuppressant Metabolism. AB - The combined clearance of endogenous 6beta-hydroxycortisol and 6beta hydroxycortisone is suggested biomarker for in vivo cytochrome P450 3A (CYP3A) activity. We aimed to determine whether the combined clearance of these two markers together with information of biopharmaceutics classification system (BCS) of drugs could be used to predict CYP3A-mediated metabolism of immunosuppressants. The BCS of drug formulations were determined based on the solubility and permeability. Sixty-seven healthy subjects were divided into three groups and group 1 (n = 23), 2 (n = 22), and 3 (n = 22) received oral single dose of cyclosporine, tacrolimus, and sirolimus, respectively. Blood and urine samples were gathered at various times. The combined clearance of 6beta-hydroxycortisol and 6beta-hydroxycortisone correlated significantly with cyclosporine pharmacokinetics (p < 0.001) after oral dose of a BCS 1 formulation, whereas no relationships were seen after administration of tacrolimus and sirolimus formulations, both of which belonged to BCS 2. Regarding the biopharmaceutical characteristics, the endogenous CYP3A biomarker explains 74.5% of variability in oral cyclosporine clearance between individuals. PMID- 26150051 TI - Endovascular stenting in malignant obstruction of superior vena cava. AB - INTRODUCTION: Superior vena cava syndrome (SVCS) is obstruction of blood flow through the SVC. It is a medical emergency and most often manifests in patients with a malignant disease process within the thorax. A patient with SVCS requires immediate diagnostic evaluation and therapy. PRESENTATION OF CASE: A 33-years-old woman presented with complaints of dyspnoea and chest pain. Computer tomography revealed a large mass in the anterior mediastinum. This mass compressed surrounding structures. Stenting was indicated for early symptoms of SVCS. The diagnosis of Hodgkin's lymphoma (HL) was confirmed with biopsy. The patient's stage II HL has been subsequently treated with six cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), followed by radiotherapy. Presently she is doing well. DISCUSSION: Although lymphomas are a common cause of SVCS but almost always SVCS is caused by non-Hodgkin's lymphoma (NHL). HL despite its common presentation with mediastinal lymphadenopathy rarely causes SVCS. CONCLUSION: Lymphomas are a common cause of SVCS in young age. HL may present as SVCS. Pathological confirmation of diagnosis should be done before initiating therapy while dealing with a case of SVCS. SVC stenting is effective and has few complications in patients with SVCS. PMID- 26150052 TI - Ranibizumab 0.5 mg for Diabetic Macular Edema with Bimonthly Monitoring after a Phase of Initial Treatment: 18-Month, Multicenter, Phase IIIB RELIGHT Study. AB - PURPOSE: To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema (DME). DESIGN: A phase IIIb, 18 month, prospective, open-label, multicenter, single-arm study in the United Kingdom. PARTICIPANTS: Participants (N = 109) with visual impairment due to DME. METHODS: Participants received 3 initial monthly ranibizumab 0.5 mg injections (day 0 to month 2), followed by individualized best-corrected visual acuity (BCVA) and optical coherence tomography-guided re-treatment with monthly (months 3-5) and subsequent bimonthly follow-up (months 6-18). Laser was allowed after month 6. MAIN OUTCOME MEASURES: Mean change in BCVA from baseline to month 12 (primary end point), mean change in BCVA and central retinal thickness (CRT) from baseline to month 18, gain of >=10 and >=15 letters, treatment exposure, and incidence of adverse events over 18 months. RESULTS: Of 109 participants, 100 (91.7%) and 99 (90.8%) completed the 12 and 18 months of the study, respectively. The mean age was 63.7 years, the mean duration of DME was 40 months, and 77.1% of the participants had received prior laser treatment (study eye). At baseline, mean BCVA was 62.9 letters, 20% of patients had a baseline BCVA of >73 letters, and mean baseline CRT was 418.1 MUm, with 32% of patients having a baseline CRT <300 MUm. The mean change in BCVA from baseline to month 6 was +6.6 letters (95% confidence interval [CI], 4.9-8.3), and after institution of bimonthly treatment the mean change in BCVA at month 12 was +4.8 letters (95% CI, 2.9-6.7; P < 0.001) and +6.5 letters (95% CI, 4.2-8.8) at month 18. The proportion of participants gaining >=10 and >=15 letters was 24.8% and 13.8% at month 12 and 34.9% and 19.3% at month 18, respectively. Participants received a mean of 6.8 and 8.5 injections over 12 and 18 months, respectively. No new ocular or nonocular safety findings were observed during the study. CONCLUSIONS: The BCVA gain achieved in the initial 6-month treatment period was maintained with an additional 12 months of bimonthly ranibizumab PRN treatment. PMID- 26150053 TI - Dyslipidemia and Diabetic Macular Edema: A Systematic Review and Meta-Analysis. AB - TOPIC: A systematic review and meta-analysis of dyslipidemia and diabetic macular edema (DME). CLINICAL RELEVANCE: Diabetic macular edema causes impairment of vision in patients with diabetes, and dyslipidemia has been reported as a risk factor for its development. A systematic review with a meta-analysis was undertaken to examine the evidence of an association between dyslipidemia and DME. METHODS: We defined eligibility criteria as randomized controlled trials (RCTs) and cohort, case-control, and cross-sectional studies reporting on the relationship between blood lipid levels and DME. We performed a literature search in MEDLINE, PubMed, and Embase from inception to September 2014. We used the Newcastle-Ottawa scale to assess the quality of case-control, cross-sectional, and cohort studies, and the Cochrane risk of bias tool for RCTs. RESULTS: The search strategy identified 4959 publications. After screening, we selected 21 articles for review (5 cross-sectional, 5 cohort, 7 case-control, and 4 RCTs). Meta-analysis of case-control studies revealed that mean levels of total serum cholesterol (TC), low-density lipoproteins (LDLs), and serum triglycerides (TGs) were significantly higher in patients with DME compared with those without DME (TC: 30.08; 95% confidence interval [CI], 21.14-39.02; P < 0.001; LDL: 18.62; 95% CI, 5.80-31.43; P < 0.05; TG: 24.82; 95% CI, 9.21-40.42; P < 0.05). Meta-analysis of RCTs did not show significant risk in worsening of hard exudates and severity of DME in the lipid-lowering group compared with placebo (hard exudates: relative risk, 1.00; 95% CI, 0.47-2.11; P = 1.00; DME: relative risk, 1.18; 95% CI, 0.75 1.86; P = 0.48). CONCLUSIONS: Despite evidence from the cohort studies and meta analysis of the case-control studies suggesting a strong relationship between lipid levels and DME, this was not confirmed by the meta-analysis that included only prospective RCTs. Therefore, given the significant public health relevance of the topic, the relationship between lipid levels and DME deserves further investigation. PMID- 26150054 TI - Conditional discrimination and response chains by worker bumblebees (Bombus impatiens Cresson, Hymenoptera: Apidae). AB - We trained worker bumblebees to discriminate arrays of artificial nectaries (one, two, and three microcentrifuge tubes inserted into artificial flowers) from which they could forage in association with their location in a three-compartmental maze. Additionally, we challenged bees to learn to accomplish three different tasks in a fixed sequence during foraging. To enter the main three-compartmented foraging arena, they had first to slide open doors in an entry box to be able to proceed to an artificial flower patch in the main arena where they had to lift covers to the artificial nectaries from which they then fed. Then, the bees had to return to the entrance way to their hive, but to actually enter, were challenged to rotate a vertically oriented disc to expose the entry hole. The bees were adept at associating the array of nectaries with their position in the compartmental maze (one nectary in compartment one, two in two, and three in three), taking about six trials to arrive at almost error-free foraging. Over all it took the bees three days of shaping to become more or less error free at the multi-step suite of sequential task performances. Thus, they had learned where they were in the chain sequence, which array and in which compartment was rewarding, how to get to the rewarding array in the appropriate compartment, and finally how to return as directly as possible to their hive entrance, open the entrance, and re-enter the hive. Our experiments were not designed to determine the specific nature of the cues the bees used, but our results strongly suggest that the tested bees developed a sense of subgoals that needed to be achieved by recognizing the array of elements in a pattern and possibly chain learning in order to achieve the ultimate goal of successfully foraging and returning to their colony. Our results also indicate that the bees had organized their learning by a hierarchy as evidenced by their proceeding to completion of the ultimate goal without reversing their foraging paths so as to return to the colony without food. PMID- 26150055 TI - The role of action prediction and inhibitory control for joint action coordination in toddlers. AB - From early in life, young children eagerly engage in social interactions. Yet, they still have difficulties in performing well-coordinated joint actions with others. Adult literature suggests that two processes are important for smooth joint action coordination: action prediction and inhibitory control. The aim of the current study was to disentangle the potential role of these processes in the early development of joint action coordination. Using a simple turn-taking game, we assessed 21/2-year-old toddlers' joint action coordination, focusing on timing variability and turn-taking accuracy. In two additional tasks, we examined their action prediction capabilities with an eye-tracking paradigm and examined their inhibitory control capabilities with a classic executive functioning task (gift delay task). We found that individual differences in action prediction and inhibitory action control were distinctly related to the two aspects of joint action coordination. Toddlers who showed more precision in their action predictions were less variable in their action timing during the joint play. Furthermore, toddlers who showed more inhibitory control in an individual context were more accurate in their turn-taking performance during the joint action. On the other hand, no relation between timing variability and inhibitory control or between turn-taking accuracy and action prediction was found. The current results highlight the distinct role of action prediction and inhibitory action control for the quality of joint action coordination in toddlers. Underlying neurocognitive mechanisms and implications for processes involved in joint action coordination in general are discussed. PMID- 26150056 TI - Psychometric properties of a shortened version of the Physical Self-Concept Questionnaire (PSQ-S). AB - INTRODUCTION: The four-dimensional model of physical self-concept which differentiates the physical self-perceptions of ability, condition, attractiveness and strength is widely accepted. In the last two decades much research has been done on the physical self-concept and its relations with the psychological well-being/distress, anxiety disorders or Eating Behavior Disorders (EBD). OBJECTIVE: To validate a shortened version of the Physical Self-Concept Questionnaire (PSQ-S) and verify its ability to discriminate between people with different levels of EBD. METHOD: Responses of 1478 subjects between 13 and 21 years old to the shortened version of the PSQ were analyzed in order to check indexes of reliability and validity. Furthermore, the scores of 96 women aged 14 to 23 years old diagnosed of EBD were compared to 96 others without clinical diagnosis. RESULTS: The results indicate a reliability of 0.93 and confirm the tetrafactorial structure of the physical selfconcept. The highest physical self concept is that of those without a clinical diagnosis of EBD. CONCLUSIONS: The Shortened-PSQ is a simple, reliable and suitable screening tool both for educational and clinical settings. It also provides a sufficient measure of physical self-concept for research purposes. PMID- 26150057 TI - The combined use of virtual reality exposure in the treatment of agoraphobia. AB - INTRODUCTION: This study compares the differential efficacy of three groups of treatments for agoraphobia: paroxetine combined with cognitive-behavioral therapy, paroxetine combined with cognitive-behavioral therapy and virtual reality exposure, and a group with only paroxetine. METHODOLOGY: 99 patients with agoraphobia were finally selected. Both combined treatment groups received 11 sessions of cognitive-behavioral therapy, and one of the groups was also exposed to 4 sessions of virtual reality treatment. Treatments were applied in individual sessions once a week for 3 months. RESULTS: The three treatment groups showed statistically significant improvements. In some measures, combined treatment groups showed greater improvements. The virtual reality exposure group showed greater improvement confronting phobic stimuli. CONCLUSIONS: Treatments combining psychopharmacological and psychological therapy showed greater efficacy. Although the use of new technologies led to greater improvement, treatment adherence problems still remain. PMID- 26150058 TI - Code 100: a study on suicidal behavior in public places. AB - Every day, the emergency departments in our country receive a large number of patients that have thought about or attempted suicide. Unfortunately, these patients are very often reluctant to maintain a regular follow-up in mental health services. In this study we describe an original program to encourage assessment and treatment of suicidal patients, particularly when they receive medical treatment in public places. We summarize the application of the program and compare the results of a specific follow-up between two groups of patients: suicidal patients assessed by emergency services in public places and all other suicidal patients assessed in the emergency department of a tertiary hospital. PMID- 26150059 TI - Systematic review of the prevalence of suicidal ideation and behavior in minors who have been sexually abused. AB - The experience of sexual abuse in childhood is a serious public health problem that is associated with suicidal behavior in numerous cases. Awareness of the relation between the experience of sexual abuse in childhood with suicidal ideation and behavior in adolescence is relevant in academic and professional terms. METHOD: A systematic review was made of published studies on the prevalence of suicide among childhood victims of sexual abuse in the European Union. Studies cited in the PsycINFO, Scopus and MEDLINE Web of Science databases were retrieved using the terms: “sexual abuse” AND “child” AND “suicide” AND “prevalence” OR “incidence”. RESULTS: The results obtained from the 16 studies reviewed show a high frequency of suicidal ideation and behavior in these victims and highlight a serious consequence of sexual abuse that seems to affect a significant number of minors. The victims of childhood sexual abuse have a 2- to 3-fold higher risk of suicidal ideation and 3- to 4-fold higher risk of attempted suicide than nonvictims. CONCLUSIONS: In the health care field, it is important to understand the specific short-term and long-term effects of childhood sexual abuse, which could improve the effectiveness of intervention in victims and treatment for those at increased risk of suicide. PMID- 26150060 TI - Clinical and evolutionary characteristics of alcoholic hallucinosis. Study of six cases. PMID- 26150061 TI - Understanding the link between sexual selection, sexual conflict and aging using crickets as a model. AB - Aging evolved because the strength of natural selection declines over the lifetime of most organisms. Weak natural selection late in life allows the accumulation of deleterious mutations and may favor alleles that have positive effects on fitness early in life, but costly pleiotropic effects expressed later on. While this decline in natural selection is central to longstanding evolutionary explanations for aging, a role for sexual selection and sexual conflict in the evolution of lifespan and aging has only been identified recently. Testing how sexual selection and sexual conflict affect lifespan and aging is challenging as it requires quantifying male age-dependent reproductive success. This is difficult in the invertebrate model organisms traditionally used in aging research. Research using crickets (Orthoptera: Gryllidae), where reproductive investment can be easily measured in both sexes, has offered exciting and novel insights into how sexual selection and sexual conflict affect the evolution of aging, both in the laboratory and in the wild. Here we discuss how sexual selection and sexual conflict can be integrated alongside evolutionary and mechanistic theories of aging using crickets as a model. We then highlight the potential for research using crickets to further advance our understanding of lifespan and aging. PMID- 26150062 TI - A review of nutritional and toxicological implications of castor bean (Ricinus communis L.) meal in animal feeding systems. AB - The nutrient-rich defatted castor meal has been tested as a potential source of protein in diets of many livestock species but has limitation due to challenges of toxins. This review was conducted to compile the relevant research information on advances in the use of raw and differently processed castor seed meal in animal feed. In this article, distribution and uses of castor and its products were identified. Research findings on the nutrients profile, principal toxins, various detoxification strategies, nutritional value and toxicity on common livestock species were compiled and reviewed. The defatted seed meal had crude protein range of 32-48%, gross energy of about 3200 kcal/kg. Ricin content was 9.3 mg/g seed, and the average RCA content was 9.9 mg/g. The meal had high activity of lectin, which produced agglutination at about 4.70 mg/ml minimum assays. Reports of detoxification strategies showed varying degrees of success but high pH, moist heating and microbial techniques appeared to exert greater effect on deactivating ricin. Detoxification strategy for the allergen component is inconclusive. Tannins and the phenolic contents were present at trace level and did not constitute notable threat. It was concluded that castor seed holds great potential as feedstuff when upgraded but such upgrading must be safe, cost effective and labour efficient for commercial acceptability. PMID- 26150064 TI - 'Healthy anorexia': The complexity of care in disordered eating. AB - This paper examines how contemporary understandings of 'health' and 'care' are engaged with and practiced by women with disordered eating. Based on findings from an Australian study investigating why people with disordered eating are reluctant to engage with treatment services (March 2012 to March 2015), we demonstrate how young women use elements of a 'health habitus' and 'care' to rationalise and justify their practices. Moving beyond Foucauldian theories of self-discipline and individual responsibility we argue that Bourdieu's concept of habitus and ethnographic concepts of care provide a deeper understanding of the ways in which people with disordered eating embody health practices as a form of care and distinction. We demonstrate how eating and bodily practices that entail 'natural', medical and ethical concerns (in particular, the new food regime known as orthorexia) are successfully incorporated into participants' eating disorder repertoires and embodied as a logic of care. Understanding how categories of health and care are tinkered with and practiced by people with disordered eating has important implications for health professionals, family members and peers engaging with and identifying people at all stages of help-seeking. PMID- 26150063 TI - When Too Much ATP Is Bad for Protein Synthesis. AB - Adenosine triphosphate (ATP) is the energy currency of living cells. Even though ATP powers virtually all energy-dependent activities, most cellular ATP is utilized in protein synthesis via tRNA aminoacylation and guanosine triphosphate regeneration. Magnesium (Mg(2+)), the most common divalent cation in living cells, plays crucial roles in protein synthesis by maintaining the structure of ribosomes, participating in the biochemistry of translation initiation and functioning as a counterion for ATP. A non-physiological increase in ATP levels hinders growth in cells experiencing Mg(2+) limitation because ATP is the most abundant nucleotide triphosphate in the cell, and Mg(2+) is also required for the stabilization of the cytoplasmic membrane and as a cofactor for essential enzymes. We propose that organisms cope with Mg(2+) limitation by decreasing ATP levels and ribosome production, thereby reallocating Mg(2+) to indispensable cellular processes. PMID- 26150066 TI - Motivations of women with sickle cell disease for asking their partners to undergo genetic testing. AB - Women with sickle cell disease (SCD) now survive well into adulthood, thus knowledge about their reproductive decision-making is becoming increasingly important to both social and medical audiences. Through in-depth interviews with 28 adult women with SCD, I explored their motivations for asking their partners to undergo prospective genetic testing. The analysis revealed several sources of motivation including participants' concerns about the potential physical suffering of future children; potential feelings of guilt and stigma; determining whether to enter or remain in an intimate relationship; and finally, their mother's lack of insisting on their father's undergo testing. These findings offer insight into the pre-conception reproductive decision-making behavior of women with SCD. PMID- 26150065 TI - Syndemics of psychosocial problems and HIV risk: A systematic review of empirical tests of the disease interaction concept. AB - In the theory of syndemics, diseases co-occur in particular temporal or geographical contexts due to harmful social conditions (disease concentration) and interact at the level of populations and individuals, with mutually enhancing deleterious consequences for health (disease interaction). This theory has widespread adherents in the field, but the extent to which there is empirical support for the concept of disease interaction remains unclear. In January 2015 we systematically searched 7 bibliographic databases and tracked citations to highly cited publications associated with the theory of syndemics. Of the 783 records, we ultimately included 34 published journal articles, 5 dissertations, and 1 conference abstract. Most studies were based on a cross-sectional design (32 [80%]), were conducted in the U.S. (32 [80%]), and focused on men who have sex with men (21 [53%]). The most frequently studied psychosocial problems were related to mental health (33 [83%]), substance abuse (36 [90%]), and violence (27 [68%]); while the most frequently studied outcome variables were HIV transmission risk behaviors (29 [73%]) or HIV infection (9 [23%]). To test the disease interaction concept, 11 (28%) studies used some variation of a product term, with less than half of these (5/11 [45%]) providing sufficient information to interpret interaction both on an additive and on a multiplicative scale. The most frequently used specification (31 [78%]) to test the disease interaction concept was the sum score corresponding to the total count of psychosocial problems. Although the count variable approach does not test hypotheses about interactions between psychosocial problems, these studies were much more likely than others (14/31 [45%] vs. 0/9 [0%]; chi2 = 6.25, P = 0.01) to incorporate language about "synergy" or "interaction" that was inconsistent with the statistical models used. Therefore, more evidence is needed to assess the extent to which diseases interact, either at the level of populations or individuals, to amplify HIV risk. PMID- 26150067 TI - Hydraulic continuity and biological effects of low strength very low frequency electromagnetic waves: Case of microbial biofilm growth in water treatment. AB - This study aims to elucidate the interactions between water, subjected to electromagnetic waves of very low frequency (VLF) (kHz) with low strength electromagnetic fields (3.5 mT inside the coils), and the development of microbial biofilms in this exposed water. Experimental results demonstrate that in water exposed to VLF electromagnetic waves, the biomass of biofilm is limited if hydraulic continuity is achieved between the electromagnetic generator and the biofilm media. The measured amount of the biofilm's biomass is approximately a factor two lower for exposed biofilm than the non-exposed biofilm. Measurements of electromagnetic fields in the air and simulations exhibit very low intensities of fields (<10 nT and 2 V/m) in the biofilm-exposed region at a distance of 1 m from the electromagnetic generator. Exposure to electric and magnetic fields of the quoted intensities cannot explain thermal and ionizing effects on the biofilm. A variable electrical potential with a magnitude close to 20 mV was detected in the tank in hydraulic continuity with the electromagnetic generator. The application of quantum field theory may help to explain the observed effects in this case. PMID- 26150068 TI - Salt tolerant plants increase nitrogen removal from biofiltration systems affected by saline stormwater. AB - Biofiltration systems are used in urban areas to reduce the concentration and load of nutrient pollutants and heavy metals entering waterways through stormwater runoff. Biofilters can, however be exposed to salt water, through intrusion of seawater in coastal areas which could decrease their ability to intercept and retain pollutants. We measured the effect of adding saline stormwater on pollutant removal by six monocotyledonous species with different levels of salt-tolerance. Carex appressa, Carex bichenoviana, Ficinia nodosa, Gahnia filum, Juncus kraussii and Juncus usitatus were exposed to six concentrations of saline stormwater, equivalent to electrical conductivity readings of: 0.09, 2.3, 5.5, 10.4, 20.0 and 37.6 mS cm(-1). Salt-sensitive species: C. appressa, C. bichenoviana and J. usitatus did not survive >=10.4 mS cm(-1), removing their ability to take up nitrogen (N). Salt-tolerant species, such as F. nodosa and J. kraussii, maintained N-removal even at the highest salt concentration. However, their levels of water stress and stomatal conductance suggest that N-removal would not be sustained at concentrations >=10.4 mS cm(-1). Increasing salt concentration indirectly increased phosphorus (P) removal, by converting dissolved forms of P to particulate forms which were retained by filter media. Salt concentrations >=10 mS cm(-1) also reduced removal efficiency of zinc, manganese and cadmium, but increased removal of iron and lead, regardless of plant species. Our results suggest that biofiltration systems exposed to saline stormwater <=10 mS cm(-1) can only maintain N-removal when planted with salt-tolerant species, while P removal and immobilisation of heavy metals is less affected by species selection. PMID- 26150069 TI - Impact of non-idealities in gas-tracer tests on the estimation of reaeration, respiration, and photosynthesis rates in streams. AB - Estimating respiration and photosynthesis rates in streams usually requires good knowledge of reaeration at the given locations. For this purpose, gas-tracer tests can be conducted, and reaeration rate coefficients are determined from the decrease in gas concentration along the river stretch. The typical procedure for analysis of such tests is based on simplifying assumptions, as it neglects dispersion altogether and does not consider possible fluctuations and trends in the input signal. We mathematically derive the influence of these non-idealities on estimated reaeration rates and how they are propagated onto the evaluation of aerobic respiration and photosynthesis rates from oxygen monitoring. We apply the approach to field data obtained from a gas-tracer test using propane in a second order stream in Southwest Germany. We calculate the reaeration rate coefficients accounting for dispersion as well as trends and uncertainty in the input signals and compare them to the standard approach. We show that neglecting dispersion significantly underestimates reaeration, and results between sections cannot be compared if trends in the input signal of the gas tracer are disregarded. Using time series of dissolved oxygen and the various estimates of reaeration, we infer respiration and photosynthesis rates for the same stream section, demonstrating that the bias and uncertainty of reaeration using the different approaches significantly affects the calculation of metabolic rates. PMID- 26150070 TI - A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia. AB - Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. PMID- 26150071 TI - [Presentation of age(ing) and elderly people in TV commercials]. AB - BACKGROUND: From the results of different studies it is known that stereotyped images about ageing and elderly people frame and influence the attitudes, beliefs and activities of elderly people and also influence the interaction of others with elderly people. OBJECTIVE: The purpose of this study was to assess the currently portrayed images of elderly people, age and ageing in television (TV) advertisements. MATERIAL AND METHODS: The study was based on a qualitative and quantitative content analysis of commercials presented on four major TV networks, two private and two public TV broadcasting networks in Germany. The sample covered 114 different commercials which included 131 elderly actors (approximately 50 + years). RESULTS: The results show that the products most often portrayed in commercials with elderly people are related to food, followed by prescription drugs and health, insurance and hygiene products. Elderly people are still underrepresented in TV commercials. Their characters are portrayed with overwhelmingly positive attributes and traits. CONCLUSION: The findings suggest that TV advertisements create an ideal image of active and healthy ageing. Further research might explore to what extent elderly people take this ideal image of ageing as their own interpretive frame of orientation. PMID- 26150072 TI - High glucose recovery from direct enzymatic hydrolysis of bisulfite-pretreatment on non-detoxified furfural residues. AB - This study reports four schemes to pretreat wet furfural residues (FRs) with sodium bisulfite for production of fermentable sugar. The results showed that non detoxified FRs (pH 2-3) had great potential to lower the cost of bioconversion. The optimal process was that unwashed FRs were first pretreated with bisulfite, and the whole slurry was then directly used for enzymatic hydrolysis. A maximum glucose yield of 99.4% was achieved from substrates pretreated with 0.1 g NaHSO3/g dry substrate (DS), at a relatively low temperature of 100 degrees C for 3 h. Compared with raw material, enzymatic hydrolysis at a high-solid of 16.5% (w/w) specifically showed more excellent performance with bisulfite treated FRs. Direct bisulfite pretreatment improved the accessibility of substrates and the total glucose recovery. Lignosulfonate in the non-detoxified slurry decreased the non-productive adsorption of cellulase on the substrate, thus improving enzymatic hydrolysis. PMID- 26150073 TI - Combined benign Brenner tumor and clear cell adenocarcinoma of the ovary. PMID- 26150075 TI - Switching among Equivalents in Chronic Cardiovascular Therapies: 'Real World' Data from Italy. AB - Since August 2012, Italian general practitioners are required to prescribe the generic name of medicines, except for refill of chronic therapy. We evaluated the extent of switching among equivalents in chronic cardiovascular therapies, the influence of the 2012 regulatory intervention and of patient-related or drug related factors. Prescriptions of off-patent anti-arrhythmics, oral antidiabetics and ACE inhibitors dispensed from August 2011 to August 2013 within the Bologna Local Health Authority (870,000 inhabitants) was collected. The rate of actual switching among equivalents was evaluated monthly. The effect of the regulatory intervention was estimated by interrupted-time-series analysis. Adjusted odds ratios (aORs) of switching were calculated for the following: age, gender, number of different equivalents available for each drug and change in dispensing pharmacy between subsequent refills. The average monthly rates of switches were 9.6%, 16.3% and 16.3% for anti-arrhythmics, antidiabetics and ACE inhibitors, respectively. Values significantly increased soon after the regulatory intervention for ACE inhibitors (+1.81%, p < 0.01), anti-arrhythmics (+1.46%, p = 0.01) and antidiabetics (+1.09%, p = 0.01), and no significant decreasing trends were observed in the following 12 months. For all drug classes, odd of switching was higher in case of change in dispensing pharmacy (up to aOR = 4.31, 95 CI = 4.26-4.35 for ACE inhibitors) and availability of >=5 different equivalents (up to aOR = 7.82, 95 CI = 7.39-8.28 for antidiabetics). Switching was lower for age >=65 for antidiabetics and ACE inhibitors (aOR = 0.92, 95 CI = 0.90-0.93; 0.87, 0.86-0.88, respectively). The Italian regulatory intervention generated an immediate increase, not sustained in time, in switching among equivalents of cardiovascular therapies. Young age, high number of available equivalents and changes in dispensing pharmacy between subsequent refills were associated with switching. PMID- 26150076 TI - A Life with Boundless Energy: a Tribute to Former AACE President, John L. Currie (1942-2015). PMID- 26150074 TI - A role for the Ca(2+)-dependent tyrosine kinase Pyk2 in tonic depolarization induced vascular smooth muscle contraction. AB - Depolarization of the plasma membrane is a key mechanism of activation of contraction of vascular smooth muscle. This is commonly achieved in isolated, de endothelialized vascular smooth muscle strips by increasing extracellular [K(+)] (replacing Na(+) by K(+)) and leads to a rapid phasic contraction followed by a sustained tonic contraction. The initial phasic contractile response is due to opening of voltage-gated Ca(2+) channels and entry of extracellular Ca(2+), which binds to calmodulin, leading to activation of myosin light chain kinase, phosphorylation of the regulatory light chains of myosin II at Ser19 and cross bridge cycling. The subsequent tonic contractile response involves, in addition to myosin light chain kinase activation, Ca(2+)-induced Ca(2+) sensitization whereby Ca(2+) entry activates the RhoA/Rho-associated kinase pathway leading to phosphorylation of MYPT1 (the myosin targeting subunit of myosin light chain phosphatase) and inhibition of the phosphatase. Investigations into the mechanism of activation of RhoA by Ca(2+) have implicated a genistein-sensitive tyrosine kinase, and recent evidence indicates this to be the Ca(2+)-dependent tyrosine kinase, Pyk2. PMID- 26150077 TI - "A Word can become a Seed": A Lesson Learned about Cultural Humility. AB - Culturally competent cancer care approaches are necessary to effectively engage ethnic and racial minorities. This reflection shares personal insights on this subject gained throughout my journey from a young immigrant to a medical and public health student in the USA. The death of a friend prompted me to explore what I had deemed as my family's taboo subjects: discussing illness, cancer, and death in the family. However, I eventually realized that it was I who perceived it as taboo subjects. When I inquired earnestly about their health beliefs and values and asked questions in a way that respected those beliefs and values, my family was quite willing to talk about these uncomfortable topics. Subsequent encounters with minority patients and the process of synthesizing this reflection helped me recognize that the way I successfully addressed what I had erroneously assumed to be taboo subjects embodied the idea of cultural humility and can also be applied to issues with other minority patients and families. This recognition will not only make me a better physician but also allow me to become a strong advocate of cultural humility, especially in cancer care and education. PMID- 26150078 TI - Venous injury in abusive head trauma. AB - BACKGROUND: Abusive head trauma (AHT) is an important cause of serious brain injury in infants and young children who have characteristic clinical and imaging findings that are discordant with the clinical history provided. Recent attention has focused on abnormalities of the cranial venous sinuses and cortical veins, both on MRI and at autopsy. Although many have interpreted these to be secondary to the AHT, some have recently argued that these venous abnormalities represent primary cortical sinus and venous thrombosis that leads secondarily to subdural hemorrhage and secondary brain injury. Direct trauma to the veins and sinuses has been reported at autopsy in AHT, but there has been no systematic study of venous abnormalities in cases of AHT. OBJECTIVE: The purpose of this study was to define the incidence and characteristics of venous and sinus abnormalities in AHT. MATERIALS AND METHODS: We included all children <36 months of age who were diagnosed with abusive head trauma between 2001 and 2012 and who had MRI and magnetic resonance (MR) venography as part of their diagnostic workup. We analyzed age, gender and clinical findings. MRI and MR venography were analyzed independently by two neuroradiologists with a focus on abnormalities involving the intracranial veins and venous sinuses. RESULTS: A total of 45 children were included. The median age was 3 months (range 15 days to 31 months) and 28 were boys (62%). Clinical findings included retinal hemorrhage in 71% and extracranial fractures in 55%. CT or MRI demonstrated subdural hemorrhage in 41 (91%); none had subdural effusions. In 31 cases (69%) MR venography demonstrated mass effect on the venous sinuses or cortical draining veins, with either displacement or partial or complete effacement of the venous structures from an adjacent subdural hematoma or brain swelling. We also describe the lollipop sign, which represents direct trauma to the cortical bridging veins and was present in 20/45 (44%) children. CONCLUSION: Evidence of displacement or compression of cortical veins and sinuses from subdural hemorrhage or edema on MR venography was present in the majority of children with abusive head trauma. Evidence of direct trauma to the veins (lollipop sign) was identified in nearly half of cases. It is important to understand the superimposed effects of subdural hematoma and brain swelling on the veins and sinuses to differentiate it from cortical sinus and venous thrombosis. PMID- 26150079 TI - Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children. AB - BACKGROUND: Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. OBJECTIVE: To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. MATERIALS AND METHODS: We retrospectively reviewed the electronic medical record to identify pediatric patients (<=18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. RESULTS: We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 +/- 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 +/- 2.2 years; range 5 weeks to 5 years) had hand administration of IV contrast agent and 30 (65%; 10.2 +/- 4.2 years; range 4-18 years) had mechanical administration of IV contrast agent. All 46 abdominal CT angiography studies were of diagnostic quality based on qualitative evaluation (all >=3). All abdominal CT angiography studies from both groups showed diagnostic quality of contrast enhancement (>150 HU) at both the celiac axis and the inferior mesenteric artery (IMA) levels. The contrast enhancement of the abdominal aorta was not significantly different between the IV contrast administration methods at either the celiac axis level (360 +/- 158 vs. 353 +/- 116, P = 0.24) or the IMA level (340 +/- 140 vs. 351 +/- 90, P = 0.27), adjusting for age. CONCLUSION: Diagnostic quality abdominal CT angiography can be achieved using hand administration of IV contrast agent in infants and young children (<=5 years). PMID- 26150081 TI - Pyrolysis of low density polyethylene waste in subcritical water optimized by response surface methodology. AB - Pyrolysis of low density polyethylene (LDPE) waste from local waste separation company in subcritical water was conducted to investigate the effect of reaction time, temperature, as well as the mass ratio of water to polymer on the liquid yield. The data obtained from the study were used to optimize the liquid yield using response surface methodology. The range of reaction temperature used was 162-338 degrees C, while the reaction time ranged from 37 min to 143 min, and the ratio of water to polymer ranged from 1.9 to 7.1. It was found that pyrolysis of LDPE waste in subcritical water produced hydrogen, methane, carbon monoxide and carbon dioxide, while the liquid product contained alkanes and alkenes with 10-50 carbons atoms, as well as heptadecanone, dichloroacetic acid and heptadecyl ester. The optimized conditions were 152.3 degrees C, reaction time of 1.2 min and ratio of water solution to polymer of 32.7, with the optimum liquid yield of 13.6 wt% and gases yield of 2.6 wt%. PMID- 26150080 TI - Functional characterization of the principal sigma factor RpoD of phytoplasmas via an in vitro transcription assay. AB - Phytoplasmas (class, Mollicutes) are insect-transmissible and plant-pathogenic bacteria that multiply intracellularly in both plants and insects through host switching. Our previous study revealed that phytoplasmal sigma factor rpoD of OY M strain (rpoDOY) could be a key regulator of host switching, because the expression level of rpoDOY was higher in insect hosts than in plant hosts. In this study, we developed an in vitro transcription assay system to identify RpoDOY-dependent genes and the consensus promoter elements. The assay revealed that RpoDOY regulated some housekeeping, virulence, and host-phytoplasma interaction genes of OY-M strain. The upstream region of the transcription start sites of these genes contained conserved -35 and -10 promoter sequences, which were similar to the typical bacterial RpoD-dependent promoter elements, while the -35 promoter elements were variable. In addition, we searched putative RpoD dependent genes based on these promoter elements on the whole genome sequence of phytoplasmas using in silico tools. The phytoplasmal RpoD seems to mediate the transcription of not only many housekeeping genes as the principal sigma factor, but also the virulence- and host-phytoplasma interaction-related genes exhibiting host-specific expression patterns. These results indicate that more complex mechanisms exist than previously thought regarding gene regulation enabling phytoplasmas to switch hosts. PMID- 26150082 TI - The effect of low-level laser therapy (LLLT) applied prior to muscle injury. AB - AIM: To evaluate the effect of LLLT (780 nm; 10 J/cm2 , 40 mW, 3.2 J) prior to injury on the morphological analysis, collagen deposition, and activity of matrix metalloproteinase-2 (MMP-2). METHODS: Wistar rats were divided into groups: control; sham; only LLLT; only muscle injury and LLLT + injury. The rats were euthanized at 1, 3, and 7 days following cryoinjury to muscle that was removed for analysis. RESULTS: LLLT applied prior to muscle injury led to a reduction in myonecrosis and inflammatory cells, an increase of blood vessels and immature muscle fibers. An increase in MMP-2 activity and a decrease in collagen deposition were also found, with a better collagen organization and distribution. CONCLUSION: LLLT applied immediately prior to injury had positive effects during the muscle regeneration process. Therefore, this resource may have considerable therapeutic value, especially for athletes who practice sports in which there is a constant risk of muscle injury. Lasers Surg. Med. 47:571-578, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26150083 TI - Twenty-Year Follow-up of Chronic Encapsulated Intracerebral Hematoma. AB - This is the first case report of a patient with chronic encapsulated intracerebral hematoma who developed excessive perifocal edema and symptoms 20 years after his initial diagnosis. PMID- 26150084 TI - Endovascular Treatment of Dissecting Aneurysms of the Posterior Inferior Cerebellar Artery and Predictors of Outcome. AB - BACKGROUND: Isolated dissecting aneurysms of the posterior inferior cerebellar artery (PICA) are rare lesions, which carry high risk of rebleeding and mortality. However, the existing literature concerning predictors of outcome after endovascular treatment is limited and controversial. Our present study retrospectively reviewed and analyzed the clinical outcome of endovascular treatment-ruptured PICA-dissecting aneurysms and explored the predictors of outcome. METHODS: We retrospectively reviewed 17 consecutive patients with ruptured PICA dissecting aneurysms that underwent endovascular treatment from January 2003 to January 2014. Nine patients underwent selective coiling, whereas 7 patients underwent parent artery occlusion and 1 patient underwent stent assisted coiling. Follow-up outcomes were evaluated using the modified Rankin Scale. The clinical outcomes of patients were categorized as favorable (modified Rankin Scale [mRS] score 0-1) or unfavorable (mRS score 2-6). RESULTS: Favorable outcomes (mRS score 0-1) were obtained in 13 of 17 patients. Post-treatment recurrence occurred in 1 patient with selective coiling in the 15-month follow up, and the patient received stent-assisted coiling. The only patients with stent assisted coiling developed PICA occlusion during follow-up. Aneurysm located in distal segment usually presented with intraventricular hemorrhage (P = .015). Hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks) were associated with unfavorable outcome. CONCLUSIONS: Endovascular treatment of isolated dissecting aneurysm of PICA had excellent clinical outcomes, hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks), which were associated with unfavorable outcome. Long-term follow ups are necessary to provide stronger conclusions. PMID- 26150085 TI - Association of Leptin Receptor Gene Polymorphisms with Genetic Susceptibility to Ischemic Stroke. AB - BACKGROUND: Ischemic stroke is a multifactorial disease that is influenced by both genetic and environmental factors. Identification of the genetic factors that are underlining this disease is important. Leptin receptor (LEPR) mediates the leptin-regulated human energy homeostasis, and mutations of LEPR can increase cardiovascular risks and may predispose an individual to ischemic stroke. METHODS: We analyzed distribution of 3 single nucleotide polymorphisms (SNPs) of LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) in 101 patients with ischemic stroke and 105 controls by polymerase chain reaction-restriction fragment length polymorphism strategy. RESULTS: Our results showed that there were significant differences in the genotype and allele distribution of Lys109Arg and Gln223Arg polymorphisms of the LEPR gene between case and control. The 109GG and 223GG genotype were associated with a significantly increased risk of ischemic stroke (odds ratio [OR], 3.23; P = .001 and OR, 2.87; P = .008, respectively). The 109G and 223G alleles carriers were correlated with an increased incidence of ischemic stroke (OR, 2.72; P = .001; OR, 2.94; P = .004). By haplotype analyses, we found that 109A/223G/656G haplotype was associated with an increased risk of ischemic stroke although this was not observed in the control group (OR, 3.86; P = .029). CONCLUSIONS: LEPR 109GG and 223GG genotypes and the 109G and 223G alleles are associated with the risk of ischemic stroke. Our data suggest that LEPR Lys109Arg and Gln223Arg polymorphisms could be used as genetic predictive factor for ischemic stroke. PMID- 26150086 TI - Direct reciprocity stabilizes simultaneous hermaphroditism at high mating rates: A model of sex allocation with egg trading. AB - Simultaneous hermaphroditism is predicted to be unstable at high mating rates given an associated increase in sperm competition. The existence of reciprocal egg trading, which requires both hermaphroditism and high mating rates to evolve, is consequently hard to explain. We show using mathematical models that the presence of a trading economy creates an additional fitness benefit to egg production, which selects for traders to bias their sex allocation toward the female function. This female-biased sex allocation prevents pure females from invading a trading population, thereby allowing simultaneous hermaphroditism to persist stably at much higher levels of sperm competition than would otherwise be expected. More generally, our model highlights that simultaneous hermaphroditism can persist stably when mating opportunities are abundant, as long as sperm competition remains low. It also predicts that reciprocity will select for heavier investment in the traded resource. PMID- 26150088 TI - Synthesis and biology of 1,4-benzodioxane lignan natural products. AB - Lignan-derived 1,4-benzodioxane natural products have been shown to exhibit a diverse array of biological activities, which has lent them to be the focus of a wealth of synthetic attention. Herein we review the background, bioactivities, biosynthesis and synthetic approaches to the 1,4-benzodioxane lignan scaffold, with an emphasis on 1,4-benzodioxane oxyneolignans. PMID- 26150087 TI - Prevalence of abnormal liver function tests in celiac disease and the effect of a gluten-free diet in the US population. AB - OBJECTIVES: Guidelines recommend routine screening of liver function tests (LFTs) in patients diagnosed with celiac disease (CD). However, little is known about the prevalence of liver disorders in CD outside of Europe. Our aims were to estimate the prevalence of LFT abnormalities in CD and to evaluate the effect of a gluten-free diet (GFD) on LFTs. METHODS: Adult patients with biopsy-proven CD were identified from a prospectively maintained database and matched with healthy controls. LFT levels for women and men were defined as abnormal based on the Third National Health and Nutrition Examination Survey (NHANES III) criteria. Data on demographics, coexisting liver diseases, and laboratory work-ups including aspartate transaminase (AST) and alanine transaminase (ALT) values at the time of diagnosis and on a GFD were recorded. Subsequently, data from this cohort were compared with data from 7,789 individuals participating in the National Health and Nutrition Examination Survey, 2009-2010. Univariate logistic regression, Wilcoxon signed-ranks, Student's t-test, chi(2), and Fischer's exact test were used for statistical analysis. RESULTS: In 463 CD patients with ALT or AST levels at the time of CD diagnosis, 40.6% had elevated LFTs compared with 24.2% of treated CD patients (P<0.001) and 16.6% of matched controls (P<0.001). Similarly, 36.7% of CD patients on the NHANES database had abnormal ALT values compared with 19.3% of non-celiac patients (P=0.03). Approximately, 78.6% of CD patients with elevated LFTs at diagnosis normalized LFTs on a GFD after a mean duration of 1.5+/-1.5 years. CONCLUSIONS: Forty percent of individuals will have elevated LFTs at CD diagnosis; however, the majority will normalize with standard CD therapy. LFTs should be checked in all patients with CD and coexisting liver disorder should be considered in patients whose LFTs have not improved within a year on a GFD. PMID- 26150089 TI - Bones in motion: Ontogeny of craniofacial development in sympatric arctic charr morphs. AB - BACKGROUND: The impressive diversity in the feeding apparatus often seen among related fish species clearly reflects differences in feeding modes and habitat utilization. Such variation can also be found within species. One example of such intraspecific diversity is the Arctic charr in Lake Thingvallavatn, where four distinct morphs coexist: two limnetic, with evenly protruding jaws, and two benthic, with subterminal lower jaws. We used these recently evolved morphs to study the role of ontogenetic variation in shaping craniofacial diversity. RESULTS: The segmental development of the pharyngeal arches and the order of events in craniofacial development is the same as has been described for teleosts, emphasizing the conserved nature of this process. However, our morphometric analyses reveal differences between morphs. Hatching is accompanied by increase in size and allometric shape changes in Arctic charr. Ontogenetic trajectories of craniofacial shape also differ significantly between morphs. CONCLUSIONS: The results point to hatching as a significant developmental event in Arctic charr and possibly other fishes. Also, the developmental origins of limnetic and benthic specializations in the craniofacial elements of Arctic charr may stem from events around hatching. This calls for investigations of the mechanisms and consequences of hatching, in the context of development and evolution. Developmental Dynamics 244:1168-1178, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26150090 TI - Confusing placebo effect with natural history in epilepsy: A big data approach. AB - For unknown reasons, placebos reduce seizures in clinical trials in many patients. It is also unclear why some drugs showing statistical superiority to placebo in one trial may fail to do so in another. Using Seizuretracker.com, a patient-centered database of 684,825 seizures, we simulated "placebo" and "drug" trials. These simulations were employed to clarify the sources of placebo effects in epilepsy, and to identify methods of diminishing placebo effects. Simulation 1 included 9 trials with a 6-week baseline and 6-week test period, starting at time 0, 3, 6...24 months. Here, "placebo" reduced seizures regardless of study start time. Regression-to-the-mean persisted only for 3 to 6 months. Simulation 2 comprised a 6-week baseline and then 2 years of follow-up. Seizure frequencies continued to improve throughout follow-up. Although the group improved, individuals switched from improvement to worsening and back. Simulation 3 involved a placebo-controlled "drug" trial, to explore methods of placebo response reduction. An efficacious "drug" failed to demonstrate a significant effect compared with "placebo" (p = 0.12), although modifications either in study start time (p = 0.025) or baseline population reduction (p = 0.0028) allowed the drug to achieve a statistically significant effect compared with placebo. In epilepsy clinical trials, some seizure reduction traditionally attributed to placebo effect may reflect the natural course of the disease itself. Understanding these dynamics will allow future investigations into optimal clinical trial design and may lead to identification of more effective therapies. Ann Neurol 2015;78:329-336. PMID- 26150091 TI - Cost-Effective Hierarchical Catalysts for Promoting Hydrogen Release from Complex Hydrides. AB - Fe nanoparticles (~10 nm), used to grow carbon nanotubes (CNTs), have an outstanding ability to catalyze the dehydrogenation of LiAlH4 . The CNTs help connect Fe and LiAlH4 and create microchannels among the composite, thus promoting the release of hydrogen. Inspired by these results, a supercritical-CO2 -fluid-assisted deposition technique is employed to decorate the Fe/CNTs with highly dispersed nanosized Ni (~2 nm in diameter) for better performance. With the incorporation of 10 wt % of this hierarchical catalyst (Ni/Fe/CNTs), the initial dehydrogenation temperature of LiAlH4 is decreased from ~135 to ~40 degrees C. At 100 degrees C, this catalyzed LiAlH4 takes only ~0.1 h to release 4.5 wt % hydrogen, which is more than 100 times faster than the time needed with pristine LiAlH4 . The dehydrogenation mechanism of the complex hydride is examined using in situ synchrotron X-ray diffraction. PMID- 26150092 TI - Perpetuation of Retracted Publications Using the Example of the Scott S. Reuben Case: Incidences, Reasons and Possible Improvements. AB - In 2009, Scott S. Reuben was convicted of fabricating data, which lead to 25 of his publications being retracted. Although it is clear that the perpetuation of retracted articles negatively effects the appraisal of evidence, the extent to which retracted literature is cited had not previously been investigated. In this study, to better understand the perpetuation of discredited research, we examine the number of citations of Reuben's articles within 5 years of their retraction. Citations of Reuben's retracted articles were assessed using the Web of Science Core Collection (Thomson Reuters, NY). All citing articles were screened to discriminate between articles in which Reuben's work was quoted as retracted, and articles in which his data was wrongly cited without any note of the retraction status. Twenty of Reuben's publications had been cited 274 times between 2009 and 1024. In 2014, 45 % of the retracted articles had been cited at least once. In only 25.8 % of citing articles was it clearly stated that Reuben's work had been retracted. Annual citations decreased from 108 in 2009 to 18 in 2014; however, the percentage of publications correctly indicating the retraction status also declined. The percentage of citations in top-25 %-journals, as well as the percentage of citations in journals from Reuben's research area, declined sharply after 2009. Our data show that even 5 years after their retraction, nearly half of Reuben's articles are still being quoted and the retraction status is correctly mentioned in only one quarter of the citations. PMID- 26150093 TI - Beyond the Ask and Advise: Implementation of a Computer Tablet Intervention to Enhance Provider Adherence to the 5As for Smoking Cessation. AB - BACKGROUND: The 5As for smoking cessation is an evidence-based intervention to aid providers in counseling patients to quit smoking. While most providers "ask" patients about their tobacco use patterns and "advise" them to quit, fewer patients report being "assessed" for their interest in quitting, and even fewer report subsequent "assistance" in a quit attempt and having follow-up "arranged". PURPOSE: This article describes the design of an implementation study testing a computer tablet intervention to improve provider adherence to the 5As for smoking cessation. Findings will contribute to the existing literature on technology acceptance for addressing addictive behaviors, and how digital tools may facilitate the broader implementation of evidence-based behavioral counseling practices without adversely affecting clinical flow or patient care. METHODS: This project develops and tests a computer-facilitated 5As (CF-5As) model that administers the 5As intervention to patients with a computer tablet, then prompts providers to reinforce next steps. During the development phase, 5As' content will be programmed onto computer tablets, alpha and beta-testing of the service delivery model will be done, and pre-intervention interview and questionnaire data will be collected from patients, providers, and clinic staff about 5As fidelity and technology adoption. During the program evaluation phase, a randomized controlled trial comparing a group who receives the CF-5As intervention to one that does not will be conducted to assess 5As fidelity. Using the technology acceptance model, a mixed methods study of contextual and human factors influencing both 5As and technology adoption will also be conducted. CONCLUSIONS: Technology is increasingly being used in clinical settings. A technological tool that connects patients, providers, and clinic staff to facilitate the promotion of behavioral interventions such as smoking cessation may provide an innovative platform through which to efficiently and effectively implement evidence-based practices. PMID- 26150094 TI - A precise spectrophotometric method for measuring sodium dodecyl sulfate concentration. AB - Sodium dodecyl sulfate (SDS) is used to denature and solubilize proteins, especially membrane and other hydrophobic proteins. A quantitative method to determine the concentration of SDS using the dye Stains-All is known. However, this method lacks the accuracy and reproducibility necessary for use with protein solutions where SDS concentration is a critical factor, so we modified this method after examining multiple parameters (solvent, pH, buffers, and light exposure). The improved method is simple to implement, robust, accurate, and (most important) precise. PMID- 26150095 TI - The UniFrac significance test is sensitive to tree topology. AB - Long et al. (BMC Bioinformatics 2014, 15(1):278) describe a "discrepancy" in using UniFrac to assess statistical significance of community differences. Specifically, they find that weighted UniFrac results differ between input trees where (a) replicate sequences each have their own tip, or (b) all replicates are assigned to one tip with an associated count. We argue that these are two distinct cases that differ in the probability distribution on which the statistical test is based, because of the differences in tree topology. Further study is needed to understand which randomization procedure best detects different aspects of community dissimilarities. PMID- 26150097 TI - Here, there, and everywhere: From PCRs to next-generation sequencing technologies and sequence databases, DNA contaminants creep in from the most unlikely places. PMID- 26150096 TI - Measuring microscale strain fields in articular cartilage during rapid impact reveals thresholds for chondrocyte death and a protective role for the superficial layer. AB - Articular cartilage is a heterogeneous soft tissue that dissipates and distributes loads in mammalian joints. Though robust, cartilage is susceptible to damage from loading at high rates or magnitudes. Such injurious loads have been implicated in degenerative changes, including chronic osteoarthritis (OA), which remains a leading cause of disability in developed nations. Despite decades of research, mechanisms of OA initiation after trauma remain poorly understood. Indeed, although bulk cartilage mechanics are measurable during impact, current techniques cannot access microscale mechanics at those rapid time scales. We aimed to address this knowledge gap by imaging the microscale mechanics and corresponding acute biological changes of cartilage in response to rapid loading. In this study, we utilized fast-camera and confocal microscopy to achieve roughly 85 um spatial resolution of both the cartilage deformation during a rapid (~3 ms), localized impact and the chondrocyte death following impact. Our results showed that, at these high rates, strain and chondrocyte death were highly correlated (p<0.001) with a threshold of 8% microscale strain norm before any cell death occurred. Additionally, chondrocyte death had developed by two hours after impact, suggesting a time frame for clinical therapeutics. Moreover, when the superficial layer was removed, strain - and subsequently chondrocyte death - penetrated deeper into the samples (p<0.001), suggesting a protective role for the superficial layer of articular cartilage. Combined, these results provide insight regarding the detailed biomechanics that drive early chondrocyte damage after trauma and emphasize the importance of understanding cartilage and its mechanics on the microscale. PMID- 26150099 TI - Management of chronic recurrent osteitis pubis/pubic bone stress in a Premier League footballer: Evaluating the evidence base and application of a nine-point management strategy. AB - BACKGROUND/AIM: The aim of this paper was to use a clinical example to describe a treatment strategy for the management of recurrent chronic groin pain and evaluate the evidence of the interventions. METHODS: A professional footballer presented with chronic recurrent OP/PBS. The injury was managed successfully with a nine-point programme - 1. Acute pharmacological management. 2. Tone reduction of over-active structures. 3. Improved ROM at hips, pelvis and thorax. 4. Adductor strength. 5. Functional movement assessment. 6. Core stability. 7. Lumbo pelvic control. 8. Gym-based strengthening. 9. Field-based conditioning/rehabilitation. The evidence for these interventions is reviewed. RESULTS: The player returned to full training and match play within 41 and 50 days, respectively, and experienced no recurrence of his symptoms in follow up at 13 months. CONCLUSION: This case report displays a nine-point conservative management strategy for OP/PBS, with non-time dependent clinical objective markers as the progression criteria in a Premier League football player. PMID- 26150100 TI - Adenosine as an Adjunct Therapy in ST Elevation Myocardial Infarction Patients: Myth or Truth? AB - Early reperfusion represents the key strategy in ST elevation myocardial infarction. However, reperfusion may induce myocardial damage due to the reperfusion myocardial injury, compromising the full potential of reperfusion therapy and accounting for unfavourable results in high risk patients. Adenosine seems to attenuate ischemia reperfusion injury, and thus represents a promising therapeutic option for treating such patients. However, previous randomized clinical trials have collectively failed to demonstrate whether adenosine can effectively reduce measures of myocardial injury and improve clinical outcome, despite its good basic evidence. The failure of such trials to show a real beneficial action may be in part related to specific factors other than adenosine's clinical efficacy. The purpose of this review is to explain the rationale for the use of adenosine as an adjunctive pharmacological cardio protective agent following reperfusion of the ischemic myocardium, to address the weakness of previous trials and to summarize the current state of knowledge regarding the effect of adenosine administration on reperfusion myocardial injury in patients with myocardial infarction. Although some preclinical and clinical studies point towards the beneficial role of adenosine in the prevention and treatment of no-reflow phenomenon in myocardial infarction, many unanswered questions still remain, including the optimal clinical indication, mode, dosage, duration and timing of application, and the exact mechanisms leading to potential benefits. Clarifying these issues will depend on further properly designed, adequately powered and well conducted clinical trials, which will probably provide us with the definite answers. PMID- 26150098 TI - G4-associated human diseases. AB - Recent research has established clear connections between G-quadruplexes and human disease. Features of quadruplex structures that promote genomic instability have been determined. Quadruplexes have been identified as transcriptional, translational and epigenetic regulatory targets of factors associated with human genetic disease. An expandable GGGGCC motif that can adopt a G4 structure, located in the previously obscure C9ORF72 locus, has been shown to contribute to two well-recognized neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This review focuses on these advances, which further dispel the view that genomic biology is limited to the confines of the canonical B-form DNA duplex, and show how quadruplexes contribute spatial and temporal dimensionalities to linear sequence information. This recent progress also has clear practical ramifications, as prevention, diagnosis, and treatment of disease depend on understanding the underlying mechanisms. PMID- 26150101 TI - Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension. AB - Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease. PMID- 26150103 TI - Amphotericin B but not itraconazole is able to prevent grain formation in experimental Madurella mycetomatis mycetoma in mice. PMID- 26150102 TI - BBS4 and BBS5 show functional redundancy in the BBSome to regulate the degradative sorting of ciliary sensory receptors. AB - Cilia harbor sensory receptors for various signaling cascades critical for vertebrate development. However, the mechanisms underlying the ciliary homeostasis of sensory receptors remain elusive. Here, we demonstrate that BBS-4 and BBS-5, two distinct BBSome components, show unexpected functional redundancy in the context of cilia in C. elegans. BBS-4 directly interacts with BBS-5 and the interaction can be disrupted by a conserved mutation identified in human BBS4. Surprisingly, we found that BBS-4 and BBS-5 act redundantly in the BBSome to regulate the ciliary removal, rather than the ciliary entry or retrograde IFT transport, of various sensory receptors. Further analyses indicate that co depletion of BBS-4 and BBS-5 disrupts the lysosome-targeted degradative sorting of ciliary sensory receptors. Moreover, mammalian BBS4 and BBS5 also interact directly and coordinate the ciliary removal of polycystin 2. Hence, we reveal a novel and highly conserved role for the BBSome in fine-tuning ciliary signaling by regulating the ciliary removal of sensory receptors for lysosomal degradation. PMID- 26150104 TI - Hydration Strategy for Endurance Running in an Athlete Requiring Home Parenteral Nutrition. AB - PURPOSE: The purpose of this report is to share our experience with optimizing home parenteral nutrition (HPN) and hydration therapy for an HPN consumer who desired to run a marathon. METHODS: A 34-year-old woman with idiopathic gastroparesis necessitating HPN and intravenous (IV) hydration desired to train for a marathon. For short runs, prerun and/or postrun hydration were adequate, but a marathon (26.2 miles) would be too long to run without IV hydration. During training, we instructed our consumer to record weights (pre/post run), ambient temperature, running distance, and duration of time. These data were used to calculate her sweat rate and estimate hydration volume during the marathon. RESULTS: Ambient temperature was a significant factor influencing sweat rate. The estimate temperature for the marathon was 65 degrees F; therefore, our consumer would have an estimated sweat rate of approximately 720 mL/h. This exceeded the amount of fluid that could be infused during the marathon; therefore, we advised our consumer to overhydrate prior to the race. Initial postrace urine output was low and concentrated but returned to baseline after postrace hydration. Our consumer did not experience any symptoms of dehydration and had only minor muscle soreness. CONCLUSIONS: Our consumer was able to complete a marathon with IV hydration. We have shown that with careful preparation, calculation, and planning, our HPN consumer was able to adequately maintain her state of hydration and accomplish her goal of running a marathon. PMID- 26150105 TI - Blenderized Tube Feeding Use in Adult Home Enteral Nutrition Patients: A Cross Sectional Study. AB - BACKGROUND: Use of long-term enteral nutrition (EN) has increased dramatically in the United States. It has been the authors' experience that most home EN (HEN) patients use blenderized tube feeding (BTF) in addition to commercial EN. There are limited resources available for patients interested in BTF, and studies evaluating safety and effectiveness are limited. METHODS: The authors conducted a prospective cross-sectional study (n = 54). INCLUSION CRITERIA: age >18 years, follow-up in HEN clinic, prescribed commercial EN. Participants were provided the survey at HEN follow-up appointments after receiving HEN for at least 3 weeks. RESULTS: Median age (range) was 60.5 (22-87) years with 42.6% females (n = 23). BTF was used by 55.5% of patients (n = 30). Most (57%; n = 31) received HEN for >6 months. BTF use was a median of 4 (1-7) days per week. Most common reasons for using BTF were as follows: it is more natural (43%), like eating what their family does (33%), and tolerate BTF better (30%). In patients who use BTF, 80% reported maintaining goal body weight. BTF resulted in significantly less reported nausea, vomiting, bloating, diarrhea, and constipation compared with commercial EN. CONCLUSIONS: This is the first study to evaluate BTF use in an adult HEN population. More than 50% of our patients used and approximately 80% expressed a desire to use BTF if provided with adequate information. With new connection tube changes coming in the near future, adequate adapters for BTF need to be developed. PMID- 26150106 TI - Parenteral Nutrition L-Cysteine Product Shortage Considerations. PMID- 26150108 TI - Climate and landscape influence on indicators of lake carbon cycling through spatial patterns in dissolved organic carbon. AB - Freshwater ecosystems are strongly influenced by both climate and the surrounding landscape, yet the specific pathways connecting climatic and landscape drivers to the functioning of lake ecosystems are poorly understood. Here, we hypothesize that the links that exist between spatial patterns in climate and landscape properties and the spatial variation in lake carbon (C) cycling at regional scales are at least partly mediated by the movement of terrestrial dissolved organic carbon (DOC) in the aquatic component of the landscape. We assembled a set of indicators of lake C cycling (bacterial respiration and production, chlorophyll a, production to respiration ratio, and partial pressure of CO2 ), DOC concentration and composition, and landscape and climate characteristics for 239 temperate and boreal lakes spanning large environmental and geographic gradients across seven regions. There were various degrees of spatial structure in climate and landscape features that were coherent with the regionally structured patterns observed in lake DOC and indicators of C cycling. These different regions aligned well, albeit nonlinearly along a mean annual temperature gradient; whereas there was a considerable statistical effect of climate and landscape properties on lake C cycling, the direct effect was small and the overall effect was almost entirely overlapping with that of DOC concentration and composition. Our results suggest that key climatic and landscape signals are conveyed to lakes in part via the movement of terrestrial DOC to lakes and that DOC acts both as a driver of lake C cycling and as a proxy for other external signals. PMID- 26150107 TI - Two short sequences in OsNAR2.1 promoter are necessary for fully activating the nitrate induced gene expression in rice roots. AB - Nitrate is an essential nitrogen source and serves as a signal to control growth and gene expression in plants. In rice, OsNAR2.1 is an essential partner of multiple OsNRT2 nitrate transporters for nitrate uptake over low and high concentration range. Previously, we have reported that -311 bp upstream fragment from the translational start site in the promoter of OsNAR2.1 gene is the nitrate responsive region. To identify the cis-acting DNA elements necessary for nitrate induced gene expression, we detected the expression of beta-glucuronidase (GUS) reporter in the transgenic rice driven by the OsNAR2.1 promoter with different lengths and site mutations of the 311 bp region. We found that -129 to -1 bp region is necessary for the nitrate-induced full activation of OsNAR2.1. Besides, the site mutations showed that the 20 bp fragment between -191 and -172 bp contains an enhancer binding site necessary to fully drive the OsNAR2.1 expression. Part of the 20 bp fragment is commonly presented in the sequences of different promoters of both the nitrate induced NAR2 genes and nitrite reductase NIR1 genes from various higher plants. These findings thus reveal the presence of conserved cis-acting element for mediating nitrate responses in plants. PMID- 26150109 TI - Role of SPECT-CT in sentinel lymph node biopsy in patients diagnosed with head and neck melanoma. AB - OBJECTIVE: Assess the role of SPECT-CT in sentinel lymph node (SLN) biopsy in the accurate anatomical location of the SNL in patients with cutaneous head and neck melanoma. MATERIAL AND METHODS: A retrospective study was conducted from February 2010 to June 2013 on 22 consecutive patients with a diagnosis of cutaneous head and neck melanoma (9 female, 13 male), with a mean age of 55 years old and who met the inclusion criteria for SLN biopsy. Patients underwent preoperative scanning after peri-scar injection of (99m)Tc-labeled-nanocolloid. Planar images of the injection-site, whole-body, and SPECT-CT scanning were acquired. RESULTS: Detection rate of SLN reached up to 91% (20/22 patients) by planar lymphoscintigraphy and 95.4% (21/22 patients) by SPECT-CT. SPECT-CT provided an accurate location of SLN in 14/22 patients, enabling to improve the surgical approach (clinical impact: 63.6%). SLN was positive for metastatic cells in 9.1% patients. CONCLUSION: SPECT-CT provides detailed anatomical SLN location and allows detecting a higher number of SLN than planar lymphoscintigraphy. Routine use of SPECT-CT is recommended in order to optimise the SLN detection and location in patients with head and neck melanoma. PMID- 26150111 TI - Call for Papers: Attention Prevention Specialists. PMID- 26150110 TI - An Examination of the Situational Factors Associated With the Misuse of Prescription Analgesics Among College Students. AB - The current study examined the effect that students' educational environment has on the prevalence and motivations associated with the misuse of prescription analgesics (MPA). A sample of 893 undergraduate students was recruited from one religiously affiliated private university and one public university in the Southern United States. Participants completed an in-class survey assessing MPA related behavior and their associated motivations. Results indicated that students attending the religiously affiliated university displayed lower rates of MPA. Multivariate analyses revealed that a positive drug abuse screening, prescription status, and grade point average are the strongest predictors of past year MPA for both schools. Some motivations for medical misuse differed significantly between campuses. Implications as to how these differences can inform programs aimed at the reduction of prescription analgesic abuse are discussed. PMID- 26150112 TI - A transparent flexible z-axis sensitive multi-touch panel based on colloidal ITO nanocrystals. AB - Bottom-up fabrication of a flexible multi-touch panel prototype based on transparent colloidal indium tin oxide (ITO) nanocrystal (NC) films is presented. A series of 7% Sn(4+) doped ITO NCs protected by oleate, octanoate and butanoate ligands are synthesized and characterized by a battery of techniques including, high resolution transmission electron microscopy, X-ray diffraction, (1)H, (13)C and (119)Sn nuclear magnetic resonance spectroscopy, and the related diffusion ordered spectroscopy. Electrical resistivities of transparent films of these NCs assembled on flexible polyethylene terephthalate substrates by convective self assembly from their suspension in toluene decrease with the ligand length, from 220 * 10(3) for oleate ITO to 13 * 10(3)Omega cm for butanoate ITO NC films. A highly transparent, flexible touch panel based on a matrix of strain gauges derived from the least resistive film of 17 nm butanoate ITO NCs sensitively detects the lateral position (x, y) of the touch as well as its intensity over the z-axis. Being compatible with a stylus or bare/gloved finger, a larger version of this module may be readily implemented in upcoming flexible screens, enabling navigation capabilities over all three axes, a feature highly desired by the display industry. PMID- 26150113 TI - Limitations in S-ICD therapy: reasons for system explantation. PMID- 26150115 TI - Three suturing techniques for closing fusiform excisions. A randomised controlled study. AB - BACKGROUND/OBJECTIVES: Australian doctors perform over one million skin excisions yearly. There are few randomised trials studying wound repair. The objective was to compare two suture techniques with controls for simple elliptical excisions in a prospective, randomised, single-blinded study. MATERIALS: One half of each wound was randomised to either one-layer closure with percutaneous nylon or modified two-layer closure where superficial closure was effected with adhesive tape. The control was the standard two-layer closure. Primary outcome measure was wound width at 6 months, with cosmesis as the secondary outcome. RESULTS: A total of 161 participants with 214 excisions were recruited from general practice. There was no significant difference in the primary outcome of wound width at 6 months between the groups. One-layer closure showed slight inferiority for cosmesis at 6 months versus the control. There was significant superiority for the modified two-layer closure versus the control for cosmesis at 6 months, and early wound erythema. Multivariate regression models adjusted for suture technique showed that younger age, wound infection and truncal location were predictors of increased scar width. Older age, wound erythema, and male gender were predictors of poorer patient-rated outcome. CONCLUSION: One-layer closure is an acceptable choice for elliptical excision wound closure. Modified two-layer closure may be preferable to standard two-layer closure for elliptical wounds. PMID- 26150114 TI - Criteria of the German Society of Cardiology for the establishment of chest pain units: update 2014. AB - Since 2008, the German Cardiac Society (DGK) has been establishing a network of certified chest pain units (CPUs). The goal of CPUs was and is to carry out differential diagnostics of acute or newly occurring chest pain of undetermined origin in a rapid and goal-oriented manner and to take immediate therapeutic measures. The basis for the previous certification process was criteria that have been established and published by the task force on CPUs. These criteria regulate the spatial and technical requirements and determine diagnostic and therapeutic strategies in patients with chest pain. Furthermore, the requirements for the organization of CPUs and the training requirements for the staff of a CPU are defined. The certification process is carried out by the DGK; currently, 225 CPUs are certified and 139 CPUs have been recertified after running for a period of 3 years. The certification criteria have now been revised and updated according to new guidelines. PMID- 26150116 TI - Does PLGA microparticle swelling control drug release? New insight based on single particle swelling studies. AB - The aim of this study was to better understand the mass transport mechanisms controlling drug release from PLGA microparticles. New insight was gained based on the experimental monitoring of single microparticle swelling. An oil-in-water (O/W) solvent extraction/evaporation method was used to prepare ketoprofen-loaded microparticles, varying the initial drug loading from 0.6 to 45.2%. Importantly, the microparticle size was kept about constant. At low ketoprofen loadings, the release patterns were clearly tri-phasic: an initial burst release was followed by a period with an about constant release rate and a final (again rapid) drug release phase. With increasing initial drug content the onset of the third release period was shifted to earlier time points. At even higher drug loadings, the release patterns became more or less bi- or mono-phasic. Interestingly, all types of microparticles showed substantial swelling after a lag-time, which coincided with the onset of the third (and again rapid) drug release phase at low loadings and proceeded it by 1 or 2d at higher drug loadings. The substantial microparticle swelling set on as soon as a critical PLGA molecular weight was reached (around 20 kDa). Thus, the onset of the third drug release phase from the PLGA microparticles might be explained as follows: once the macromolecules are sufficiently short, substantial amounts of water penetrate into the system, significantly increasing the mobility of the drug within the microparticles and resulting in increased drug release rates. PMID- 26150117 TI - VISA--Vector Integration Site Analysis server: a web-based server to rapidly identify retroviral integration sites from next-generation sequencing. AB - BACKGROUND: Analyzing the integration profile of retroviral vectors is a vital step in determining their potential genotoxic effects and developing safer vectors for therapeutic use. Identifying retroviral vector integration sites is also important for retroviral mutagenesis screens. RESULTS: We developed VISA, a vector integration site analysis server, to analyze next-generation sequencing data for retroviral vector integration sites. Sequence reads that contain a provirus are mapped to the human genome, sequence reads that cannot be localized to a unique location in the genome are filtered out, and then unique retroviral vector integration sites are determined based on the alignment scores of the remaining sequence reads. CONCLUSIONS: VISA offers a simple web interface to upload sequence files and results are returned in a concise tabular format to allow rapid analysis of retroviral vector integration sites. PMID- 26150118 TI - Statewide Hospital Discharge Data: Collection, Use, Limitations, and Improvements. AB - OBJECTIVES: To provide an overview of statewide hospital discharge databases (HDD), including their uses in health services research and limitations, and to describe Agency for Healthcare Research and Quality (AHRQ) Enhanced State Data grants to address clinical and race-ethnicity data limitations. PRINCIPAL FINDINGS: Almost all states have statewide HDD collected by public or private data organizations. Statewide HDD, based on the hospital claim with state variations, contain useful core variables and require minimal collection burden. AHRQ's Healthcare Cost and Utilization Project builds uniform state and national research files using statewide HDD. States, hospitals, and researchers use statewide HDD for many purposes. Illustrating researchers' use, during 2012-2014, HSR published 26 HDD-based articles on health policy, access, quality, clinical aspects of care, race-ethnicity and insurance impacts, economics, financing, and research methods. HDD have limitations affecting their use. Five AHRQ grants focused on enhancing clinical data and three grants aimed at improving race ethnicity data. CONCLUSION: ICD-10 implementation will significantly affect the HDD. The AHRQ grants, information technology advances, payment policy changes, and the need for outpatient information may stimulate other statewide HDD changes. To remain a mainstay of health services research, statewide HDD need to keep pace with changing user needs while minimizing collection burdens. PMID- 26150119 TI - Probability bounds analysis for nonlinear population ecology models. AB - Mathematical models in population ecology often involve parameters that are empirically determined and inherently uncertain, with probability distributions for the uncertainties not known precisely. Propagating such imprecise uncertainties rigorously through a model to determine their effect on model outputs can be a challenging problem. We illustrate here a method for the direct propagation of uncertainties represented by probability bounds though nonlinear, continuous-time, dynamic models in population ecology. This makes it possible to determine rigorous bounds on the probability that some specified outcome for a population is achieved, which can be a core problem in ecosystem modeling for risk assessment and management. Results can be obtained at a computational cost that is considerably less than that required by statistical sampling methods such as Monte Carlo analysis. The method is demonstrated using three example systems, with focus on a model of an experimental aquatic food web subject to the effects of contamination by ionic liquids, a new class of potentially important industrial chemicals. PMID- 26150120 TI - Inhibition of pathogenic and spoilage bacteria by a novel biofilm-forming Lactobacillus isolate: a potential host for the expression of heterologous proteins. AB - BACKGROUND: Bacterial biofilms are a preferred mode of growth for many types of microorganisms in their natural environments. The ability of pathogens to integrate within a biofilm is pivotal to their survival. The possibility of biofilm formation in Lactobacillus communities is also important in various industrial and medical settings. Lactobacilli can eliminate the colonization of different pathogenic microorganisms. Alternatively, new opportunities are now arising with the rapidly expanding potential of lactic acid bacteria biofilms as bio-control agents against food-borne pathogens. RESULTS: A new isolate Lactobacillus plantarum PA21 could form a strong biofilm in pure culture and in combination with several pathogenic and food-spoilage bacteria such as Salmonella enterica, Bacillus cereus, Pseudomonas fluorescens, and Aeromonas hydrophila. Exposure to Lb. plantarum PA21 significantly reduced the number of P. fluorescens, A. hydrophila and B. cereus cells in the biofilm over 2-, 4- and 6 day time periods. However, despite the reduction in S. enterica cells, this pathogen showed greater resistance in the presence of PA21 developed biofilm, either in the planktonic or biofilm phase. Lb. plantarum PA21 was also found to be able to constitutively express GFP when transformed with the expression vector pMG36e which harbors the gfp gene as a reporter demonstrating that the newly isolated strain can be used as host for genetic engineering. CONCLUSION: In this study, we evaluate the ability of a new Lactobacillus isolate to form strong biofilm, which would provide the inhibitory effect against several spoilage and pathogenic bacteria. This new isolate has the potential to serve as a safe and effective cell factory for recombinant proteins. PMID- 26150121 TI - The development and evaluation of an evidence-based guideline programme to improve care in a paediatric emergency department. AB - INTRODUCTION: Care guidelines can improve the quality of care by making current evidence available in a concise format. Emergency departments (EDs) are an ideal site for guidelines given the wide variety of presenting conditions and treating providers, and the need for timely decision making. We designed a programme for guideline development and implementation and evaluated its impact in an ED. METHODS: The setting was an urban paediatric ED with an annual volume of 60 000. Common and/or high-risk conditions were identified for guideline development. Following implementation of the guidelines, their impact on effectiveness of care, patient outcomes, efficiency and equitability of care was assessed using a web-based provider survey and performance on identified metrics. Variation in clinical care between providers was assessed using funnel plots. RESULTS: Eleven (11) guidelines were developed and implemented. 3 years after the initiation of the programme, self-reported adherence to recommendations was high (95% for physicians and 89% for nurses). 97% of physicians and 92% of nurses stated that the programme improved the quality of care in the ED. For some guidelines, provider-to-provider care practice variation was reduced significantly. We found reduced disparity in imaging when assessing one guideline. There were also reductions in utilisation of diagnostic tests or therapies. As a balancing measure, the percentage of patients with any of the guideline conditions who returned to the ED within 72 h of discharge did not change from before to after guideline initiation. Overall, 80% of physician and 56% of nurse respondents rated the guideline programme at the highest value. CONCLUSIONS: A programme for guideline development and implementation helped to improve efficiency, and standardise and eliminate disparities in emergency care without jeopardising patient outcomes. PMID- 26150123 TI - Connective tissue diseases: Neutrophil extracellular traps--a mechanism of thrombosis in patients with antiphospholipid syndrome? PMID- 26150124 TI - Rheumatoid arthritis: Debunking the obesity-mortality paradox in RA. PMID- 26150125 TI - Epidemiology research in rheumatology-progress and pitfalls. AB - Epidemiology research is a vital component of clinical studies in all medical fields. This Review provides a brief introduction to the methodology and interpretation of population and clinical epidemiology studies of musculoskeletal disorders. Data sources (including 'big data' and the issue of missing data), study design (cross-sectional, case-control and cohort studies, including clinical trial design) and the interpretation of study results are discussed with examples from the field of rheumatology, particularly using findings in patients with rheumatoid arthritis. Two or more treatments can be compared in clinical trials using a variety of study designs including superiority, noninferiority or equivalence. The different types of risk in epidemiological studies-absolute, attributable, background and relative-are important concepts in epidemiological research and their relative usefulness to clinicians and patients should be considered carefully. The potential pitfalls and challenges of generalizing the results of epidemiological studies to understanding disease aetiology and to clinical practice are also emphasized. The aim of the Review is to help readers to critically appraise published articles that use epidemiological designs or methods. PMID- 26150126 TI - Gout: Why compare the effectiveness of suboptimal gout management? AB - Comparative effectiveness research could help inform the choice of agent for urate-lowering therapy, the central component of successful gout management. However, if such studies reflect current clinical practice, are they comparing poor management with inadequate management? PMID- 26150128 TI - Erratum to: hCLP46 increases Smad3 protein stability via inhibiting its ubiquitin proteasomal degradation. PMID- 26150129 TI - Interactive effects of pesticide exposure and pathogen infection on bee health - a critical analysis. AB - Bees are fundamentally important for pollination services and declines in populations could have significant economic and environmental implications. Pesticide exposure and pathogen infection are recognised as potential stressors impacting upon bee populations and recently there has been a surge in research on pesticide-disease interactions to reflect environmentally realistic scenarios better. We critically analyse the findings on pesticide-disease interactions, including effects on the survival, pathogen loads and immunity of bees, and assess the suitability of various endpoints to inform our mechanistic understanding of these interactions. We show that pesticide exposure and pathogen infection have not yet been found to interact to affect worker survival under field-realistic scenarios. Colony-level implications of pesticide effects on Nosema infections, viral loads and honey bee immunity remain unclear as these effects have been observed in a laboratory setting only using a small range of pesticide exposures, generally exceeding those likely to occur in the natural environment, and assessing a highly selected series of immune-related endpoints. Future research priorities include the need for a better understanding of pesticide effects on the antimicrobial peptide (AMP) component of an individual's immune response and on social defence behaviours. Interactions between pesticide exposure and bacterial and fungal infections have yet to be addressed. The paucity of studies in non-Apis bee species is a further major knowledge gap. PMID- 26150130 TI - Transparent carbon nanotube network for efficient electrochemiluminescence devices. AB - A carbon nanotube-based electrode that combines transparency and good conductivity was used for the first time to develop an electrochemiluminescence (ECL) device. It resulted in an excellent material for ECL applications thanks to the very favorable overpotential of amine oxidation that represents the rate determining step for the signal generation in both research systems and commercial instrumentation. The use of carbon nanotubes resulted in a ten times higher emission efficiency compared with commercial transparent indium tin oxide (ITO) electrodes. Moreover, application of this material for proof-of-principle ECL imaging was demonstrated, in which micro-beads were used to mimic a real biological sample in order to prove the possibility of obtaining single cell visualization. PMID- 26150127 TI - Global epidemiology of gout: prevalence, incidence and risk factors. AB - Gout is a crystal-deposition disease that results from chronic elevation of uric acid levels above the saturation point for monosodium urate (MSU) crystal formation. Initial presentation is mainly severely painful episodes of peripheral joint synovitis (acute self-limiting 'attacks') but joint damage and deformity, chronic usage-related pain and subcutaneous tophus deposition can eventually develop. The global burden of gout is substantial and seems to be increasing in many parts of the world over the past 50 years. However, methodological differences impair the comparison of gout epidemiology between countries. In this comprehensive Review, data from epidemiological studies from diverse regions of the world are synthesized to depict the geographic variation in gout prevalence and incidence. Key advances in the understanding of factors associated with increased risk of gout are also summarized. The collected data indicate that the distribution of gout is uneven across the globe, with prevalence being highest in Pacific countries. Developed countries tend to have a higher burden of gout than developing countries, and seem to have increasing prevalence and incidence of the disease. Some ethnic groups are particularly susceptible to gout, supporting the importance of genetic predisposition. Socioeconomic and dietary factors, as well as comorbidities and medications that can influence uric acid levels and/or facilitate MSU crystal formation, are also important in determining the risk of developing clinically evident gout. PMID- 26150133 TI - Primary leiomyosarcoma of the breast with prominent osteoclastic giant cells: A case expressing receptor activator of NF-kappaB ligand (RANKL). AB - Primary sarcomas of the breast are rare, accounting for less than 1% of all breast neoplasms. Leiomyosarcoma is one of the least common breast sarcoma subtypes, and less than 50 cases of primary breast leiomyosarcomas have been reported in the English literature. In other types of leiomyosarcoma, osteoclastic giant cells (OGCs) are occasionally admixed with tumor cells; however, this is rarely seen in primary breast leiomyosarcoma. We herein present the case of a 50-year-old woman with OGC-containing primary breast leiomyosarcoma whose tumor cells showed positive immunostaining for receptor activator of NF kappaB ligand (RANKL). The presence of OGCs in tumors generally indicates tumor aggressiveness. This is true for leiomyosarcoma of the soft tissue and might be true for leiomyosarcoma of primary breast origin. Regarding RANKL expression, in giant cell tumor of bone (GCTB) in which OGCs expressing RANK were abundant, tumor cells are known for expressing RANKL. Therapy targeting RANKL decreases the number of tumor cells of GCTB. Our findings are clinically relevant as they indicate that RANKL expression should be investigated in various tumors containing OGCs. This might lead to the development of future molecule-targeted therapy. PMID- 26150131 TI - Effectiveness of an interdisciplinary palliative care intervention for family caregivers in lung cancer. AB - BACKGROUND: Family caregivers (FCGs) experience significant deteriorations in quality of life while caring for patients with lung cancer. In this study, the authors tested the effectiveness of an interdisciplinary palliative care intervention for FCGs of patients diagnosed with stage I through IV nonsmall cell lung cancer. METHODS: FCGs who were identified by patients as their primary caregivers were enrolled in a prospective, quasi-experimental study in which the usual care group was accrued first followed by the intervention group. FCGs in the intervention group were presented at interdisciplinary care meetings, and they also received 4 educational sessions organized in the physical, psychological, social, and spiritual domains. The sessions included self-care plans to support the FCG's own needs. Caregiver burden, caregiving skills preparedness, psychological distress, and FCG quality of life were assessed at baseline and after 12 weeks using validated measures. RESULTS: In total, 366 FCGs were included in the primary analysis. FCGs who received the interdisciplinary palliative care intervention had significantly better scores for social well being (5.84 vs 6.86; P < .001) and had lower psychological distress scores (4.61 vs 4.20; P = .010) at 12 weeks compared with FCGs in the usual care group. FCGs in the intervention group also had significantly less caregiver burden compared with FCGs in the usual care group (P = .008). CONCLUSIONS: An interdisciplinary approach to palliative care in lung cancer resulted in statistically significant improvements in FCG's social well being and psychological distress and in less caregiver burden. PMID- 26150132 TI - The key role of coligands in novel ruthenium(II)-cyclopentadienyl bipyridine derivatives: Ranging from non-cytotoxic to highly cytotoxic compounds. AB - A new family of eight ruthenium(II)-cyclopentadienyl bipyridine derivatives, bearing nitrogen, sulfur, phosphorous and carbonyl sigma bonded coligands, has been synthesized. Compounds bearing nitrogen bonded coligands were found to be unstable in aqueous solution, while the others presented appropriate stabilities for the biologic assays and pursued for determination of IC50 values in ovarian (A2780) and breast (MCF7 and MDAMB231) human cancer cell lines. These studies were also carried out for the [5: HSA] and [6: HSA] adducts (HSA=human serum albumin) and a better performance was found for the first case. Spectroscopic, electrochemical studies by cyclic voltammetry and density functional theory calculations allowed us to get some understanding on the electronic flow directions within the molecules and to find a possible clue concerning the structural features of coligands that can activate bipyridyl ligands toward an increased cytotoxic effect. X-ray structure analysis of compound [Ru(eta(5) C5H5)(bipy)(PPh3)][PF6] (7; bipy=bipyridine) showed crystallization on C2/c space group with two enantiomers of the [Ru(eta(5)-C5H5)(bipy)(PPh3)](+) cation complex in the racemic crystal packing. PMID- 26150134 TI - Cross-sensitization between testosterone and cocaine in adolescent and adult rats. AB - Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats. PMID- 26150135 TI - Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders. AB - Autism spectrum disorder (ASD) is a neurological disorder that presents a spectrum of qualitative impairments in social interaction, communication, as well as restricted and stereotyped behavioral patterns, interests, and activities. Several studies have suggested that the etiology of ASD can be partly explained by oxidative stress. However, the implications of abnormal transsulfuration metabolism and oxidative stress, and their relation with ASD are still unclear. The purpose of this study was to evaluate several transsulfuration pathway metabolites in Chinese participants diagnosed with ASD, to better understand their role in the etiology of this disorder. Fifty children (39 male, 11 female) diagnosed with ASD and 50 age- and gender-matched non-ASD children (i.e., control group) were included in this study. This prospective blinded study was undertaken to assess transsulfuration and oxidative metabolites, including levels of homocysteine (Hcy), cysteine (Cys), total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), and glutathione ratio (GSH/GSSG). The clinical severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS), and the autistic children's present behavior was measured by the Autism Behavior Checklist (ABC). The results indicated that Hcy and GSSG levels were significantly higher in children diagnosed with ASD, Cys, tGSH and GSH levels as well as the GSH/GSSG ratio showed remarkably lower values in ASD children compared to control subjects. Hcy levels correlated significantly with increasing CARS scores and GSSG levels in children with ASD. Our results suggest that an abnormal transsulfuration metabolism and reduced antioxidant capacity (i.e., hyperhomocysteinemia and increased oxidative stress), and Hcy level appears to have a potentially negative impact on clinical severity of autistic disorder. PMID- 26150136 TI - Genetic instability in plants associated with vehicular traffic and climatic variables. AB - To characterize the effect of vehicular traffic on air quality, the micronuclei of Tradescantia pallida tetrads were counted. Young inflorescences of T. pallida (Rose) D.R. Hunt var. purpurea were collected in 2010, 2011, and 2012, from three sites subjected to different intensities of vehicular traffic. The sites were located in the municipality of Dourados, in the State of Mato Grosso do Sul, Brazil. A standardized methodology was used to analyze the Tradescantia micronuclei, in order to evaluate the mutagenic potential of the local air pollutants. Statistical analyses using the Pearson's linear correlation were employed to determine the relationship between relative humidity and temperature, and the average number of micronuclei. In this study, an increase in the average number of passing vehicles was correlated with an increase in the frequency of micronucleus formation. Climatic factors also influenced micronucleus formation, although vehicular traffic remained the most important factor. Thus, the Tradescantia micronuclei assay may be a useful method of assessing air quality. PMID- 26150137 TI - Transgenic cry1C(*) gene rough rice line T1C-19 does not change the host preferences of the non-target stored product pest, Rhyzopertha dominica (Fabricius) (Coleoptera: Bostrichidae), and its parasitoid wasp, Anisopteromalus calandrae (Howard) (Hymenoptera: Pteromalidae). AB - Rough rice grains are often stored for extended periods before they are used or consumed. However, during storage, the rough rice is vulnerable to insect infestation, resulting in significant economic loss. Previous studies have shown that volatiles cues, physical characteristics, and taste chemicals on the grains could be the important key behavior factors for storage insect pests to locate the hosts and select oviposition sites. It is also well known that the transgenic Bt rough rice line T1C-19, which expresses a cry1C(*) gene has a high resistance to Lepidoptera pests. However, there were no evidences to show the consequences of host preference for non-target insect pests after growing Bt transgenic rice. In this study, the potential key factors of Bt rough rice were investigated for their impacts on the behaviors of non-target pest lesser grain borer Rhyzopertha dominica, the main weevil pest of grain and its parasitic wasps Anisopteromalus calandrae, the natural enemy of the beetle. Both electronic nose and electronic tongue analyses showed that the parameters of Bt rough rice were analogous to those of the non-Bt rough rice. The volatile profiles of Bt and non-Bt rough rice examined by gas chromatographic mass spectrometry (GC-MS) were similar. For most volatile compounds, there were no significantly quantitative differences in compound quantities between Bt and non-Bt rough rice. The densities of sclereids and trichomes on the rough rice husk surface were statistically equal in Bt and non-Bt rough rice. The non-target pest, R. dominica, and its parasitoid wasp, A. calandrae, were attracted to both rough rice and could not distinguish the transgenic T1C-19 from the isogenic rough rice. These results demonstrated that Bt rough rice has no negative impacts on the host preference behaviors of non target stored product pest R. dominica and its parasitoid A. calandrae. PMID- 26150138 TI - Developmental role of plk4 in Xenopus laevis and Danio rerio: implications for Seckel Syndrome. AB - The polo-like kinases are a family of conserved serine/threonine kinases that play multiple roles in regulation of the cell cycle. Unlike its four other family members, the role of Plk4 in embryonic development has not been well characterized. In mice, Plk4(-)(/)(-) embryos arrest at E7.5, just prior to the initiation of somitogenesis. This has led to the hypothesis that Plk4 expression may be essential to somitogenesis. Recently characterized human mutations lead to Seckel Syndrome. Riboprobe in situ hybridization revealed that plk4 is ubiquitously expressed during early stages of development of Xenopus and Danio; in later stages, expression in frogs restricts to somites as well as eye, otic vesicle, and branchial arch, and brain. Expression patterns in fish remain ubiquitous. Both somite and eye development require planar cell polarity, and disruption of plk4 function in frog by means of morpholino-mediated translational knockdown yields orientational disorganization of both these structures. These results provide the first steps in defining a new role for plk4 in organogenesis and implies a role in planar cell polarity, segmentation, and in recently described PLK4 mutations in human. PMID- 26150139 TI - Antioxidant potential of indigenous cyanobacterial strains in relation with their phenolic and flavonoid contents. AB - Antioxidant activities of eight indigenous cyanobacterial strains belonging to the genera Oscillatoria, Chroococcidiopsis, Leptolyngbya, Calothrix, Nostoc and Phormidium were studied in relation with their phenolic and flavonoid contents, ranging 3.9-12.6 mg GAE g(-1) and 1.7-3.44 mg RE g(-1). The highest activities were shown by Leptolyngbya sp. SI-SM (EC50 = 63.45 and 67.49 MUg mL(-1)) and Calothrix sp. SI-SV (EC50 = 65.79 and 69.38 MUg mL(-1)) calculated with ABTS and DPPH assays. Significant negative correlations were seen between total phenolic and flavonoid contents and the antioxidant activities in terms of EC50 values. Furthermore, HPLC detected 15 phenolic compounds with total concentrations ranging from 277.3 to 829.7 MUg g(-1). The prevalent compounds in most of the strains were rutin, tannic acid, orcinol, phloroglucinol and protocatechuic acid. Cyanobacterial strains showed high potential as a good source of phenolic compounds with potent antioxidative potential which could be beneficial for food, cosmetic and pharmaceutical industries. PMID- 26150140 TI - The growth of alpha-sexithiophene films on Ag(111) studied by means of PEEM with linearly polarized light. AB - In this study, we used photo electron emission microscopy (PEEM) to investigate the growth of alpha-sexithiophene (alpha-6 T) on Ag(111) surfaces. The experiments were carried out with linearly polarized ultraviolet-light (Hg lamp with hnu=4.9 eV) in order to probe the alignment of the molecules on the surface. In particular, we acquired images before, during, and after growth while changing the polarization in a stepwise manner. For the stationary states of the clean and the alpha-6 T covered surfaces, we monitored the local electron yield and the intensity of the ultraviolet C-light (100-280 nm) reflected from the whole sample using PEEM and a photodiode, respectively. Due to the high ionization potential (IP>5 eV), there is no direct photoelectron emission from the organic crystallites. However, the photoelectron emission of the metal/organic interface is influenced by anisotropic absorption of the incident light beam, since the adsorbed molecules act as dichroic filters with distinct orientations. PMID- 26150141 TI - Development of a computerised decisions support system for renal risk drugs targeting primary healthcare. AB - OBJECTIVES: To assess general practitioners (GPs) experience from the implementation and use of a renal computerised decision support system (CDSS) for drug dosing, developed for primary healthcare, integrated into the patient's electronic health record (EHR), and building on estimation of the patient's creatinine clearance (ClCG). DESIGN: Qualitative research design by a questionnaire and a focus group discussion. SETTING AND PARTICIPANTS: Eight GPs at two primary healthcare centres (PHCs). INTERVENTIONS: The GP at PHC 1, and the project group, developed and tested the technical solution of the CDSS. Proof-of concept was tested by seven GPs at PHC 2. They also participated in a group discussion and answered a questionnaire. A web window in the EHR gave drug and dosage in relation to ClCG. Each advice was according to three principles: If? Why? Because. OUTCOME MEASURES: (1) The GPs' experience of 'easiness to use' and 'perceived usefulness' at PHC 2, based on loggings of use, answers from a questionnaire using a 5-point Likert scale, and answers from a focus group discussion. (2) The number of patients aged 65 years and older with an estimation of ClCG before and after the implementation of the CDSS. RESULTS: The GPs found the CDSS fast, simple and easy to use. They appreciated the automatic presentation of the CICG status on opening the medication list, and the ability to actively look up specific drug recommendations in two steps. The CDSS scored high on the Likert scale. All GPs wanted to continue the use of the CDSS and to recommend it to others. The number of patients with an estimated ClCG increased 1.6-fold. CONCLUSIONS: Acceptance of the simple graphical interface of this push and pull renal CDSS was high among the primary care physicians evaluating this proof of concept. The graphical model should be useful for further development of renal decision support systems. PMID- 26150142 TI - A systematic review of the predictors of health service utilisation by adults with mental disorders in the UK. AB - OBJECTIVES: To identify variables that predict health service utilisation (HSU) by adults with mental disorders in the UK, and to determine the evidence level for these predictors. DESIGN: A narrative synthesis of peer-reviewed studies published after the year 2000. The search was conducted using four databases (ie, PsycINFO, CINAHL Plus with full text, MEDLINE and EMBASE) and completed on 25 March 2014. SETTING: The majority of included studies were set in health services across primary, secondary, specialist and inpatient care. Some studies used data from household and postal surveys. PARTICIPANTS: Included were UK-based studies that predicted HSU by adults with mental disorders. Participants had a range of mental disorders including psychotic disorders, personality disorders, depression, anxiety disorders, eating disorders and dementia. PRIMARY OUTCOME: A wide range of HSU outcomes were examined, including general practitioner (GP) contacts, medication usage, psychiatrist contacts, psychotherapy attendances, inpatient days, accident and emergency admissions and 'total HSU'. RESULTS: Taking into account study quality, 28 studies identified a range of variables with good preliminary evidence supporting their ability to predict HSU. Of these variables, comorbidity, personality disorder, age (heterogeneous age ranges), neurotic symptoms, female gender, a marital status of divorced, separated or widowed, non-white ethnicity, high previous HSU and activities of daily living, were associated with increased HSU. Moreover, good preliminary evidence was found for associations of accessing a primary care psychological treatment service and medication use with decreased HSU. CONCLUSIONS: The findings can inform decisions about which variables might be used to derive mental health clusters in 'payment by results' systems in the UK. The findings also support the need to investigate whether combining broad diagnoses with care pathways is an effective method for mental health clustering, and the need for research to further examine the association between mental health clusters and HSU. PMID- 26150143 TI - How family carers engage with technical health procedures in the home: a grounded theory study. AB - OBJECTIVES: To explore the experiences of family carers who manage technical health procedures at home and describe their learning process. DESIGN: A qualitative study using grounded theory. PARTICIPANTS: New Zealand family carers (21 women, 5 men) who managed technical health procedures such as enteral feeding, peritoneal dialysis, tracheostomy care, a central venous line or urinary catheter. In addition, 15 health professionals involved in teaching carers were interviewed. METHODS: Semistructured interviews were coded soon after completion and preliminary analysis influenced subsequent interviews. Additional data were compared with existing material and as analysis proceeded, initial codes were grouped into higher order concepts until a core concept was described. Interviewing continued until no new ideas emerged and concepts were well defined. RESULTS: The response of carers to the role of managing technical health procedures in the home is presented in terms of five dispositions: (1) Embracing care, (2) Resisting, (3) Reluctant acceptance, (4) Relinquishing and (5) Being overwhelmed. These dispositions were not static and carers commonly changed between them. Embracing care included cognitive understanding of the purpose and benefits of a procedure; accepting a 'technical' solution; practical management; and an emotional response. Accepting embrace is primarily motivated by perceived benefits for the recipient. It may also be driven by a lack of alternatives. Resisting or reluctant acceptance results from a lack of understanding about the procedure or willingness to manage it. Carers need adequate support to avoid becoming overwhelmed, and there are times when it is appropriate to encourage them to relinquish care for the sake of their own needs. CONCLUSIONS: The concept of embracing care encourages health professionals to extend their attention beyond simply the practical aspects of technical procedures to assessing and addressing carers' emotional and behavioural responses to health technology during the training process. PMID- 26150145 TI - Women's interpretation of and responses to potential gynaecological cancer symptoms: a qualitative interview study. AB - OBJECTIVE: To explore women's experiences of symptoms potentially indicative of gynaecological cancer in a community-based sample without imposing a cancer perspective. DESIGN: A qualitative interview study with thematic analysis of transcripts. PARTICIPANTS: 26 women aged >=30 years, who had experienced a symptom that might indicate gynaecological cancer in the past 3 months, were recruited using a screening questionnaire distributed online and in community settings. SETTING: London, UK. RESULTS: Women attributed gynaecological symptoms to existing illnesses/conditions or considered themselves to be predisposed to them, either through their 'genes' or previous personal experience. Normalising symptoms by attributing them to demographic characteristics (eg, age, sex) was common, as was considering them a side effect of hormonal contraception. When women raised cancer as a possible cause, they often dismissed it as unlikely. Responses to symptoms included self-management (eg, self-medicating, making lifestyle changes), adopting a 'lay system of care', or consulting a healthcare professional. Triggers to help-seeking included persistent, painful or debilitating symptoms, concern about symptom seriousness, and feeling that help seeking was legitimised. Barriers to help-seeking included lack of concern, vague symptoms, unusual symptom location, competing time demands, previous negative experiences with the healthcare system, and not wanting to be perceived as a time waster. CONCLUSIONS: Attributions of symptoms potentially indicative of a gynaecological cancer were varied, but most often involved women fitting symptoms into their expectations of what was 'normal'. Normalising acted as a barrier to seeking help from a healthcare professional, alongside competing time demands and negative attitudes towards help-seeking. These barriers may lead to later diagnosis and poorer cancer survival. Our findings could be used to inform the development of interventions to encourage appropriate help-seeking. PMID- 26150144 TI - A cross-sectional study of the prevalence and associations of iron deficiency in a cohort of patients with chronic obstructive pulmonary disease. AB - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Iron deficiency, with or without anaemia, is associated with other chronic conditions, such as congestive heart failure, where it predicts a worse outcome. However, the prevalence of iron deficiency in COPD is unknown. This observational study aimed to determine the prevalence of iron deficiency in COPD and associations with differences in clinical phenotype. SETTING: University hospital outpatient clinic. PARTICIPANTS: 113 adult patients (65% male) with COPD diagnosed according to GOLD criteria (forced expiratory volume in 1 s (FEV1): forced vital capacity (FVC) ratio <0.70 and FEV1 <80% predicted); with age-matched and sex-matched control group consisting of 57 healthy individuals. MAIN OUTCOME MEASURES: Prevalence of iron deficiency, defined as: any one or more of (1) soluble transferrin receptor >28.1 nmol/L; (2) transferrin saturation <16% and (3) ferritin <12 ug/L. Severity of hypoxaemia, including resting peripheral arterial oxygen saturation (SpO2) and nocturnal oximetry; C reactive protein (CRP); FEV1; self-reported exacerbation rate and Shuttle Walk Test performance. RESULTS: Iron deficiency was more common in patients with COPD (18%) compared with controls (5%). In the COPD cohort, CRP was higher in patients with iron deficiency (median 10.5 vs 4.0 mg/L, p<0.001), who were also more hypoxaemic than their iron-replete counterparts (median resting SpO2 92% vs 95%, p<0.001), but haemoglobin concentration did not differ. Patients with iron deficiency had more self-reported exacerbations and a trend towards worse exercise tolerance. CONCLUSIONS: Non-anaemic iron deficiency is common in COPD and appears to be driven by inflammation. Iron deficiency associates with hypoxaemia, an excess of exacerbations and, possibly, worse exercise tolerance, all markers of poor prognosis. Given that it has been shown to be beneficial in other chronic diseases, intravenous iron therapy should be explored as a novel therapeutic option in COPD. PMID- 26150146 TI - Exploring the Evolution of Cortical Excitability Following Acute Stroke. AB - BACKGROUND: Evolution of changes in intracortical excitability following stroke, particularly in the contralesional hemisphere, is being increasingly recognized in relation to maximizing the potential for functional recovery. OBJECTIVE: The present study utilized a prospective longitudinal design over a 12-month period from stroke onset, to investigate the evolution of intracortical excitability involving both motor cortices and their relationship to recovery, and whether such changes were influenced by baseline stroke characteristics. METHODS: Thirty one patients with acute unilateral ischemic stroke were recruited from a tertiary hospital stroke unit. Comprehensive clinical assessments and cortical excitability were undertaken at stroke onset using a novel threshold-tracking paired-pulse transcranial magnetic stimulation technique, and repeated at 3-, 6-, and 12-month follow-up in 17 patients who completed the longitudinal assessment. RESULTS: Shortly following stroke, short-interval intracortical inhibition (SICI) was significantly reduced in both lesioned and contralesional hemispheres that correlated with degree of recovery over the subsequent 3 months. Over the follow up period, ipsilesional SICI remained reduced in all patient groups, while SICI over the contralesional hemisphere remained reduced only in the groups with cortical stroke or more baseline functional impairment. CONCLUSIONS: The current study has demonstrated that evolution of intracortical excitability, particularly over the contralesional hemisphere, may vary between patients with differing baseline stroke and clinical characteristics, suggesting that ongoing contralesional network recruitment may be necessary for those patients who have significant disruptions to the integrity of ipsilesional motor pathways. Results from the present series have implications for the development of neuromodulatory brain stimulation protocols to harness and thereby facilitate stroke recovery. PMID- 26150149 TI - [Hemiparesis and reduced strength in a racing cyclist: Result of an unusual incident]. PMID- 26150147 TI - Success of Anomia Treatment in Aphasia Is Associated With Preserved Architecture of Global and Left Temporal Lobe Structural Networks. AB - BACKGROUND AND OBJECTIVE: Targeted speech therapy can lead to substantial naming improvement in some subjects with anomia following dominant-hemisphere stroke. We investigated whether treatment-induced improvement in naming is associated with poststroke preservation of structural neural network architecture. METHODS: Twenty-four patients with poststroke chronic aphasia underwent 30 hours of speech therapy over a 2-week period and were assessed at baseline and after therapy. Whole brain maps of neural architecture were constructed from pretreatment diffusion tensor magnetic resonance imaging to derive measures of global brain network architecture (network small-worldness) and regional network influence (nodal betweenness centrality). Their relationship with naming recovery was evaluated with multiple linear regressions. RESULTS: Treatment-induced improvement in correct naming was associated with poststroke preservation of global network small worldness and of betweenness centrality in temporal lobe cortical regions. Together with baseline aphasia severity, these measures explained 78% of the variability in treatment response. CONCLUSIONS: Preservation of global and left temporal structural connectivity broadly explains the variability in treatment-related naming improvement in aphasia. These findings corroborate and expand on previous classical lesion-symptom mapping studies by elucidating some of the mechanisms by which brain damage may relate to treated aphasia recovery. Favorable naming outcomes may result from the intact connections between spared cortical areas that are functionally responsive to treatment. PMID- 26150150 TI - Interferon lambda 3 and 4 Genotyping Using High-Resolution Melt Curve Analysis Suitable for Multiple Clinical Sample Types. AB - Many people living with hepatitis C virus (HCV) infection will continue to rely on interferon-based regimens until effective strategies to minimize the cost of directly acting antivirals (DAAs) and to improve treatment access are implemented. Host single-nucleotide polymorphisms related to IFNL3 and IFNL4 are associated with spontaneous clearance of HCV, and pegylated interferon- and DAA based treatment outcomes. We describe a simple and rapid genotyping method for IFNL rs12979860, rs8099917, and rs368234815 using high-resolution melting analysis for DNA extracted from whole blood, buffy coat, plasma, serum, and dried blood spots. This assay successfully detected all three polymorphisms on DNA extracted by the automated platform easyMAG from all samples when compared to sequenced amplicons. Analysis of 126 participants with recent HCV infection from the Australian Trial in Acute Hepatitis C study demonstrated the prevalence of favorable single-nucleotide polymorphisms were 62%, 51%, and 45% for rs8099917 TT, rs12979860 CC, and rs368234815 TT/TT, respectively. The genotyping assay described here provides a rapid and affordable IFNL3 and IFNL4 genotyping method for a range of clinical sample types. Until global access to DAAs is achieved, IFNL3 and IFNL4 genotyping could identify those likely to clear naturally and in whom treatment could be delayed, or help prioritize DAA treatment to those less likely to respond to interferon-containing regimens. PMID- 26150151 TI - Quantitative evaluation of CART-containing cells in urinary bladder of rats with renovascular hypertension. AB - Recent biological advances make it possible to discover new peptides associated with hypertension. The cocaine- and amphetamine-regulated transcript (CART) is a known factor in appetite and feeding behaviour. Various lines of evidence suggest that this peptide participates not only in control of feeding behaviour but also in the regulation of the cardiovascular and sympathetic systems and blood pressure. The role of CART in blood pressure regulation led us to undertake a study aimed at analysing quantitative changes in CART-containing cells in urinary bladders (UB) of rats with renovascular hypertension. We used the Goldblatt model of arterial hypertension (two-kidney, one clip) to evaluate quantitative changes. This model provides researchers with a commonly used tool to analyse the renin angiotensin system of blood pressure control and, eventually, to develop drugs for the treatment of chronic hypertension. The study was performed on sections of urinary bladders of rats after 3-, 14-, 28-, 42 and 91 days from hypertension induction. Immunohistochemical identification of CART cells was performed on paraffin for the UBs of all the study animals. CART was detected in the endocrine cells, especially numerous in the submucosa and muscularis layers, with a few found in the transitional epithelium and only occasionally in serosa. Hypertension significantly increased the number of CART-positive cells in the rat UBs. After 3 and 42 days following the procedure, statistically significantly higher numbers of CART-positive cells were identified in comparison with the control animals. The differences between the hypertensive rats and the control animals concerned not only the number density of CART-immunoreactive cells but also their localization. After a 6-week period, each of the rats subjected to the renal artery clipping procedure developed stable hypertension. CART appeared in numerous transitional epithelium cells. As this study provides novel findings, the question appears about the type of connection between hypertension and the functioning and activity of CART in the urinary tract (UT). The study gives rise to the assumption that high blood pressure can be a factor that intensifies CART secretion. In conclusion, the endocrine system of the urinary tract is modified by renovascular hypertension. This may affect the production of hormones and biologically active substances and contribute to the development of possible hypertension complications. In order to fully comprehend the role of the CART peptide in blood pressure regulation, further analyses are necessary. PMID- 26150152 TI - ECRG4 expression in normal rat tissues: expression study and literature review. AB - The Esophageal Cancer Related Gene 4 (ECRG4) is a highly conserved tumour suppressor gene encoding various peptides (augurin, CDelta16 augurin, ecilin, argilin, CDelta16 argilin) which can be processed and secreted. In the present work, we examined ECRG4 expression and location in a wide range of rat organs and reviewed the available literature. ECRG4 mRNA was identified in all examined tissues by quantitative PCR (qPCR). ECRG4 immunoreaction was mainly cytoplasmic, and was detected in heart and skeletal muscles, smooth muscle cells showing only weak reactions. In the digestive system, ECRG4 immunostaining was stronger in the esophageal epithelium, bases of gastric glands, hepatocytes and pancreatic acinar epithelium. In the lymphatic system, immunoreactive cells were detectable in the thymus cortex, lymph node medulla and splenic red pulp. In the central and peripheral nervous systems, different neuronal groups showed different reaction intensities. In the endocrine system, ECRG4 immunoreaction was detected in the hypothalamic paraventricular and supraoptic nuclei, hypophysis, thyroid and parathyroid glands, adrenal zona glomerularis and medulla and Leydig cells, as well as in follicular and luteal cells of the ovary. In the literature, ECRG4 has been reported to inhibit cell proliferation and increase apoptosis in various cell types. It is down-regulated, frequently due to hypermethylation, in esophageal, prostate, breast and colon cancers, together with glioma (oncosuppressor function), although it is up-regulated in papillary thyroid cancer (oncogenic role). ECRG4 expression is also higher in non-proliferating cells of the lymphatic system. In conclusion, our identification of ECRG4 in many structures suggests the involvement of ECRG4 in the tumorigenesis of other organs and also the need for further research. In addition, on the basis of the location of ECRG4 in neurons and endocrine cells and the fact that it can be secreted, its role as a neurotransmitter/neuromodulator and endocrine factor must be examined in depth in the future. PMID- 26150153 TI - Apigenin induces dermal collagen synthesis via smad2/3 signaling pathway. AB - Decrease in fibroblast-produced collagen has been proven to be the pivotal cause of skin aging, but there is no satisfactory drug which directly increases dermal thickness and collage density. Here we found that a flavonoid natural product, apigenin, could significantly increase collagen synthesis. NIH/3T3 and primary human dermal fibroblasts (HDFs) were incubated with various concentrations of apigenin, with dimethyl sulfoxide (DMSO) serving as the negative control. Real time reverse-transcription polymerase chain reaction (PCR), Western Blot, and Toluidine blue staining demonstrated that apigenin stimulated type-I and type-III collagen synthesis of fibroblasts on the mRNA and protein levels. Meanwhile, apigenin did not induce expression of alpha smooth muscle actin (alpha-SMA) in vitro and in vivo, a fibrotic marker in living tissues. Then the production of collagen was confirmed by Masson's trichrome stain, Picrosirius red stain and immunohistochemistry in mouse models. We also clarified that this compound induced collagen synthesis by activating smad2/3 signaling pathway. Taken together, without obvious influence on fibroblasts' apoptosis and viability, apigenin could promote the type-I and type-III collagen synthesis of dermal fibroblasts in vitro and in vivo, thus suggesting that apigenin may serve as a potential agent for esthetic and reconstructive skin rejuvenation. PMID- 26150154 TI - Histological and histochemical analysis of the gastrointestinal tract of the common pipistrelle bat (Pipistrellus pipistrellus). AB - Bats have a very high mass-specific energy demand due to small size and active flight. European bat species are mostly insectivorous and the morphology of the gastrointestinal tract should be adapted accordingly. This study investigated the general anatomy by histology and the function by analysing carbohydrate distribution in particular of the mucus of the GI tract of the insectivorous bat Pipistrellus pipistrellus. The GI tracts of three individuals were dissected, fixed in formaldehyde, and embedded in paraffin wax. The tissues and cells of the GI tract of P. pipistrellus were analysed by classical (Acid Alizarin Blue, Haematoxylin-Eosin, and Masson Goldner Trichrome), histochemical (periodic acid Schiff, Alcian blue at pH 2.5) and lectin histochemical (lectins WGA and HPA) staining procedures. The GI tract of P. pipistrellus was organised into the typical mammalian layers. The short, narrow, and thin-walled esophagus was simple with a folded stratified squamous epithelium without glands but mucous surface cells secreting neutral mucus. The stomach was globular shaped without specialisation. Mucous surface cells produced neutral mucus whereas neck and parietal cells secreted a mixture of neutral and acid mucus. Chief cell surface was positive for N-acetylglucosamine and the cytoplasm for N-acetylgalactosamine residues. The intestine lacked a caecum and appendix. The small intestine was divided into duodenum, jejunum-ileum and ileum-colon. The epithelium consisted of columnar enterocytes and goblet cells. The large intestine was short, only represented by the descending colon-rectum. It lacked villi and the mucosa had only crypts of Lieberkuhn. Towards the colon-rectum, goblet cells produced mucus with N-acetylglucosamine residues increasing in acidity except in colon-rectum where acidity was highest in the base of crypts. Along the tube the surface of enterocytes was positive for N-acetylglucosamine and N-acetylgalactosamine. All over the mucus filling the lumen of the GI tract was positive for N acetylglucosamine and increased in acidity in all parts except of the stomach. In conclusion, the simple GI tract showed an anatomical reduction of tissue enabling for a short retention time and a reduction of the load carried during flight: short GI tract, lack of lymphoid tissue, missing of glands in certain regions, and a distinct pattern of mucus distribution, indicating different physiological functions of these areas. The GI tract of P. pipistrellus was typical for an insectivorous species probably representing the ancestral condition. PMID- 26150155 TI - Reliable LC3 and p62 autophagy marker detection in formalin fixed paraffin embedded human tissue by immunohistochemistry. AB - Autophagy assures cellular homeostasis, and gains increasing importance in cancer, where it impacts on carcinogenesis, propagation of the malignant phenotype and development of resistance. To date, its tissue-based analysis by immunohistochemistry remains poorly standardized. Here we show the feasibility of specifically and reliably assessing the autophagy markers LC3B and p62 (SQSTM1) in formalin fixed and paraffin embedded human tissue by immunohistochemistry. Preceding functional experiments consisted of depleting LC3B and p62 in H1299 lung cancer cells with subsequent induction of autophagy. Western blot and immunofluorescence validated antibody specificity, knockdown efficiency and autophagy induction prior to fixation in formalin and embedding in paraffin. LC3B and p62 antibodies were validated on formalin fixed and paraffin embedded cell pellets of treated and control cells and finally applied on a tissue microarray with 80 human malignant and non-neoplastic lung and stomach formalin fixed and paraffin embedded tissue samples. Dot-like staining of various degrees was observed in cell pellets and 18/40 (LC3B) and 22/40 (p62) tumors, respectively. Seventeen tumors were double positive for LC3B and p62. P62 displayed additional significant cytoplasmic and nuclear staining of unknown significance. Interobserver-agreement for grading of staining intensities and patterns was substantial to excellent (kappa values 0.60 - 0.83). In summary, we present a specific and reliable IHC staining of LC3B and p62 on formalin fixed and paraffin embedded human tissue. Our presented protocol is designed to aid reliable investigation of dysregulated autophagy in solid tumors and may be used on large tissue collectives. PMID- 26150156 TI - Receptor-mediated endocytosis of lysozyme in renal proximal tubules of the frog Rana temporaria. AB - The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endosomes), and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intracellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals. PMID- 26150157 TI - Developmental expression of inositol 1, 4, 5-trisphosphate receptor in the post natal rat cochlea. AB - Inositol 1, 4, 5-trisphosphate receptor (IP3R) has been established to be essential for hearing. However, the expression of IP3R in the cochlea in the period of auditory development remains unknown. We investigated the expression of IP3R in the developing rat cochlea using immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). We observed its presence in the developing rat cochlea, and changes in IP3R protein expressions from the early post-natal period to adult. At birth (post-natal day 0, P0), IP3R expression was only found in Hensen's cell. IP3R immunoreactivity first appeared in the sensory hair cells in the organ of Corti at P2. This localization was confirmed by means of double-labeling experiments with Myosin VIIA, a marker for cochlear hair cells. Colocalization of IP3R and Myosin VIIA from P2 to the second post-natal week suggested early expression of IP3R in developing inner and outer hair cells. Claudius' cells near the spiral ligament were labelled for IP3R from P8 onwards. Transient IP3R expression was observed in the stria vascularis in early post-natal rat from P4 to P8. Spiral ganglion neurons also exhibited weaker IP3R fluorescence signals during post-natal development. The results of RT-PCR demonstrated that all three IP3R isoforms (IP3R1, IP3R2, and IP3R3) were present in rat cochlea during four different developmental stages of cochlea, from P0 to P28. Present immunohistochemical evidence for both change and maintenance of expression of IP3R during post-natal development of the rat cochlea indicated the possible involvement of IP3R-mediated calcium signaling in cochlear development. PMID- 26150158 TI - Infection with CagA-positive Helicobacter pylori strain containing three EPIYA C phosphorylation sites is associated with more severe gastric lesions in experimentally infected Mongolian gerbils (Meriones unguiculatus). AB - Infection with Helicobacter pylori strains containing high number of EPIYA-C phosphorylation sites in the CagA is associated with significant gastritis and increased risk of developing pre-malignant gastric lesions and gastric carcinoma. However, these findings have not been reproduced in animal models yet. Therefore, we investigated the effect on the gastric mucosa of Mongolian gerbil (Meriones unguiculatus) infected with CagA-positive H. pylori strains exhibiting one or three EPIYA-C phosphorilation sites. Mongolian gerbils were inoculated with H. pylori clonal isolates containing one or three EPIYA-C phosphorylation sites. Control group was composed by uninfected animals challenged with Brucella broth alone. Gastric fragments were evaluated by the modified Sydney System and digital morphometry. Clonal relatedness between the isolates was considered by the identical RAPD-PCR profiles and sequencing of five housekeeping genes, vacA i/d region and of oipA. The other virulence markers were present in both isolates (vacA s1i1d1m1, iceA2, and intact dupA). CagA of both isolates was translocated and phosphorylated in AGS cells. After 45 days of infection, there was a significant increase in the number of inflammatory cells and in the area of the lamina propria in the infected animals, notably in those infected by the CagA positive strain with three EPIYA-C phosphorylation sites. After six months of infection, a high number of EPIYA-C phosphorylation sites was associated with progressive increase in the intensity of gastritis and in the area of the lamina propria. Atrophy, intestinal metaplasia, and dysplasia were also observed more frequently in animals infected with the CagA-positive isolate with three EPIYA-C sites. We conclude that infection with H. pylori strain carrying a high number of CagA EPIYA-C phosphorylation sites is associated with more severe gastric lesions in an animal model of H. pylori infection. PMID- 26150159 TI - WT1 expression in the human fetus during development. AB - Wilms' Tumor 1 (WT1) is a transcription factor involved in the development of the urogenital system. The purpose of this study was to analyze the immunoreactivity for WT1 protein in different tissues and organs in human fetuses in early phases of gestation. To this end, samples from multiple organs were obtained from 4 human fetuses, ranging from 7 up to 12 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained for WT1. Our data show that WT1 is involved in development of multiple human organs in a more vast series of cells types than previously reported. Immunostaining for WT1 was characterized by a predominant cytoplasmic reactivity in the vast majority of cell types. Mesenchimal progenitors in the fetal lung, ductal plate progenitors in fetal liver, cap mesenchimal cells in the developing kidney, fetal zone cells in adrenal glands, atrial and ventricular cardiomyocytes in the fetal heart, radial glial cells in the fetal cerebral cortex and skeletal muscle cell precursors showed the highest levels of WT1 immunoreactivity. Future studies will be needed to detect differences in the expression of WT1 in various organs at different gestational ages, in order to better evaluate the role of WT1 in cell proliferation and differentiation during intrauterine human development. PMID- 26150160 TI - Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns. AB - Unlike its application for atherosclerotic plaque analysis, Raman microspectroscopy was sporadically used to check the sole nature of bioapatite deposits in stenotic aortic valves, neglecting the involvement of accumulated lipids/lipoproteins in the calcific process. Here, Raman microspectroscopy was employed for examination of stenotic aortic valve leaflets to add information on nature and distribution of accumulated lipids and their correlation with mineralization in the light of its potential precocious diagnostic use. Cryosections from surgically explanted stenotic aortic valves (n=4) were studied matching Raman maps against specific histological patterns. Raman maps revealed the presence of phospholipids/triglycerides and cholesterol, which showed spatial overlapping with one another and Raman-identified hydroxyapatite. Moreover, the Raman patterns correlated with those displayed by both von-Kossa-calcium- and Nile-blue-stained serial cryosections. Raman analysis also provided the first identification of carotenoids, which co-localized with the identified lipid moieties. Additional fit concerned the distribution of collagen and elastin. The good correlation of Raman maps with high-affinity staining patterns proved that Raman microspectroscopy is a reliable tool in evaluating calcification degree, alteration/displacement of extracellular matrix components, and accumulation rate of different lipid forms in calcified heart valves. In addition, the novel identification of carotenoids supports the concept that valve stenosis is an atherosclerosis-like valve lesion, consistently with their previous Raman microspectroscopical identification inside atherosclerotic plaques. PMID- 26150161 TI - Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study. AB - The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status. PMID- 26150162 TI - Low ozone concentrations stimulate cytoskeletal organization, mitochondrial activity and nuclear transcription. AB - Ozone therapy is a modestly invasive procedure based on the regeneration capabilities of low ozone concentrations and used in medicine as an alternative/adjuvant treatment for different diseases. However, the cellular mechanisms accounting for the positive effects of mild ozonization are still largely unexplored. To this aim, in the present study the effects of low ozone concentrations (1 to 20 ug O3/mL O2) on structural and functional cell features have been investigated in vitro by using morphological, morphometrical, cytochemical and immunocytochemical techniques at bright field, fluorescence and transmission electron microscopy. Cells exposed to pure O2 or air served as controls. The results demonstrated that the effects of ozoneadministration are dependent on gas concentration, and the cytoskeletal organization, mitochondrial activity and nuclear transcription may be differently affected. This suggests that, to ensure effective and permanent metabolic cell activation, ozone treatments should take into account the cytological and cytokinetic features of the different tissues. PMID- 26150163 TI - Incorporation of a GPI-anchored engineered cytokine as a molecular adjuvant enhances the immunogenicity of HIV VLPs. AB - HIV vaccines should elicit immune responses at both the mucosal portals of entry to block transmission and systemic compartments to clear disseminated viruses. Co delivery of mucosal adjuvants has been shown to be essential to induce effective mucosal immunity by non-replicating vaccines. A novel cytokine, GIFT4, engineered by fusing GM-CSF and interleukin-4, was previously found to simulate B cell proliferation and effector function. Herein a membrane-anchored form of GIFT4 was constructed by fusing a glycolipid (GPI)-anchoring sequence and incorporated into Env-enriched HIV virus-like particles (VLPs) as a molecular adjuvant. Guinea pigs were immunized with the resulting HIV VLPs through an intramuscular priming intranasal boosting immunization route. The GIFT4-containing VLPs induced higher levels of systemic antibody responses with significantly increased binding avidity and improved neutralizing breadth and potency to a panel of selected strains, as well as higher levels of IgG and IgA at several mucosal sites. Thus, the novel GPI-GIFT4-containging VLPs have the potential to be developed into a prophylactic HIV vaccine. Incorporation of GPI-anchored GIFT4 into VLPs as a molecular adjuvant represents a novel approach to increase their immunogenicity. PMID- 26150164 TI - Polyclonal neural cell adhesion molecule antibody prolongs the effective duration time of botulinum toxin in decreasing muscle strength. AB - This study aimed to investigate if the effective duration time of botulinum toxin A (Btx-A) could be prolonged by polyclonal neural cell adhesion molecule antibody (P-NCAM-Ab). 175 male SD rats were randomly divided into three major groups: control group (n = 25), Btx-A group (n = 25), and P-NCAM-Ab groups. P-NCAM-Ab groups were composed of five sub-groups, with 25 rats each in the dose-response study. Muscle strength of rat lower limbs was determined using a survey system. The expressions of muscle-specific receptor tyrosine kinase (MuSK) and neural cell adhesion molecule (NCAM) were determined by real-time polymerase chain reactions (RT-PCR) and western blotting (WB). The muscle strength was significantly decreased by Btx-A in Btx-A/P-NCAM-Ab groups compared with normal control group. Besides, the muscle strength of P-NCAM-Ab group was significantly decreased compared with the Btx-A group. The recovery time of muscle strength in P-NCAM-Ab group was significantly longer compared with Btx-A group. RT-PCR and WB assay showed that PNCAM-Ab delayed the increase of MuSK and NCAM after Btx-A injection. P-NCAM-Ab prolongs the effective duration time of Btx-A in decreasing muscle strength, which could provide a novel enhancement in clinical application. PMID- 26150165 TI - Erratum to: The Italian Registry of Endovascular Treatment in Acute Stroke: rationale, design and baseline features of patients. PMID- 26150166 TI - Meta-analysis of associations between MTHFR and GST polymorphisms and susceptibility to multiple sclerosis. AB - We examined whether methylenetetrahydrofolate reductase (MTHFR) and glutathione S transferase (GST) polymorphisms are associated with susceptibility to multiple sclerosis (MS). We performed a meta-analysis on the association between MS and the following genotypes: MTHFR C677T, A1298C, and GSTP1 A313G polymorphisms, and GSTM1 and GSTT1 null alleles. Fifteen comparisons involving 2,486 patients and 2,861 controls were considered. Meta-analysis of all study subjects considered together showed no association between MS and the MTHFR 677 T allele (OR = 1.014, 95 % CI 0.803-1.280, p = 0.909). Stratification by ethnicity showed no similar association in Caucasian and Arab populations. Likewise, no link was found between MS and the MTHFR 1298 C allele in the total data (OR = 2.477, 95 % CI 0.507-12.10, p = 0.263), nor when it was stratified by ethnicity. No association with MS was observed in relation to the GSTM1 null genotype in Caucasian populations (OR = 1.229, 95 % CI 0.693-2.181, p = 0.481), nor with the GSTP1 A313G polymorphism (OR for G allele = 1.133, 95 % CI 0.903-1.421, p = 0.281). However, there was an association between MS and the GSTT1 null genotype in data obtained from Caucasian populations (OR = 1.945, 95 % CI 1.452-2.605, p = 8.6 * 10(-7)). GSTT1 null genotype is associated with MS in Caucasian populations; however, no association was found between MS and polymorphisms of MTHFR, GSTM1, and GSTP1. PMID- 26150167 TI - Promoting Physical Activity Through a Manual Wheelchair Propulsion Intervention in Persons With Multiple Sclerosis. AB - OBJECTIVE: To examine the efficacy and feasibility of a multifactorial intervention to increase lifestyle physical activity in nonambulatory persons with multiple sclerosis (MS) based on wheelchair optimization, propulsion skill/technique training, and behavioral strategies based on social cognitive theory. DESIGN: Randomized controlled trial, 3-month postintervention follow-up. SETTING: Home and general community, and university research laboratory. PARTICIPANTS: Nonambulatory individuals with MS (N=14; mean age +/- SD, 53.6+/ 8.7y) were randomly assigned to an intervention group (IG) or a control group (CG). INTERVENTIONS: After baseline testing, the IG participants received custom fit, ultralightweight manual wheelchairs with propulsion/skills training, followed by 3 months of at-home use with the custom ultralightweight wheelchair and weekly phone calls to deliver support through a multifactorial intervention. The CG participants received no training and used their own wheelchairs at home during this time. MAIN OUTCOME MEASURES: All subjects were assessed at baseline and 3 months later for fatigue (Fatigue Severity Scale), upper extremity strength (digital handheld dynamometer), and propulsion technique (on a treadmill [0.5m/s] with instrumented wheels). Two 1-week bouts of physical activity were measured in both groups from home with wrist-worn accelerometry at the beginning (IG and CG in own wheelchairs) and end (IG in study wheelchair, CG in own) of the 3-month period of home use. RESULTS: The intervention was well tolerated, and no adverse events were reported. The IG demonstrated increased strength (P=.008) and a trend toward less fatigue (P=.068), both with large effect sizes (d>0.8), as well as reduced application of braking torque during propulsion (P=.003) with a moderate/large effect size (d=.73), compared with the CG. CONCLUSIONS: Findings suggest a 3-month physical activity intervention based on manual wheelchair propulsion and training is safe and feasible for some wheelchair users living with MS and may produce secondary benefits in strength, fatigue, and propulsion technique. PMID- 26150168 TI - Genetic control of the environmental variance for birth weight in seven generations of a divergent selection experiment in mice. AB - Data from seven generations of a divergent selection experiment designed for environmental variability of birth weight were analysed to estimate genetic parameters and to explore signs of selection response. A total of 10 783 birth weight records from 638 females and 1127 litters in combination with 10 007 pedigree records were used. Each record of birth weight was assigned to the mother of the pup in a heteroscedastic model, and after seven generations of selection, evidence of success in the selection process was shown. A Bayesian analysis showed that success of the selection process started from the first generation for birth weight and from the second generation for its environmental variability. Genetic parameters were estimated across generations. However, only from the third generation onwards were the records useful to consider the results to be reliable. The results showed a consistent positive and low genetic correlation between the birth weight trait and its environmental variability, which could allow an independent selection process. This study has demonstrated that the genetic control of the birth weight environmental variability is possible in mice. Nevertheless, before the results are applied directly in farm animals, it would be worth confirming any other implications on other important traits, such as robustness, longevity and welfare. PMID- 26150169 TI - Carpal tunnel syndrome and prediabetes: is there a true association? AB - BACKGROUND: Carpal tunnel syndrome (CTS) is probably associated with diabetes mellitus, but its link to prediabetes (PD) is unknown. OBJECTIVE: To determine prevalence of PD and others risk factors in CTS. METHODS: A cross-sectional study including 115 idiopathic CTS patients and 115 age-, gender-and body mass index (BMI)-matched controls was performed. Clinical, laboratory and neurophysiological evaluations were conducted in all subjects to confirm CTS diagnosis. CTS severity was graded on a standardized neurophysiological scale. PD was defined using strict criteria. RESULTS: The prevalence of PD was similar in CTS and control groups (27% vs. 21.7%, respectively P=0.44). Nocturnal symptoms (91.3%) and moderate CTS (58.3%) were most frequently observed in CTS patients. In logistic regression analysis, PD was significantly correlated with age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.09; P=0.006) and BMI (OR 1.08. 95% CI 1.01-1.16; P=0.026), but not with CTS (OR 0.82, 95% CI 0.43-1.53; P=0.537). CTS patients with PD had a significantly higher mean age compared to those without PD (53.8+/-10.2 vs. 49.5+/-8.6 years, respectively P=0.027). The frequency of age >60 years was significantly higher in CTS with PD than in CTS without PD (29.0% vs. 8.3%, respectively P=0.04) as was BMI >30kg/m(2) (64.5% vs. 33.3%, respectively P=0.03). No significant differences were observed between the two CTS groups with respect to gender, BMI, symptoms, and neurophysiological severity of CTS. CONCLUSIONS: Our findings indicated that CTS is not associated with PD, but that PD is closely linked to age and overweight. PMID- 26150170 TI - The role of epigenetic mediation and the future of food allergy research. AB - IgE-mediated food allergy is a developing global health problem with prevalence rising at alarmingly fast rates. In this review, we discuss the interplay between genetics, epigenetics, and environmental exposures in the pathogenesis of food allergies. We aim to highlight the most recent evidence that suggests how epigenetic control may mediate genetic susceptibility of food allergies. We also examine how epigenetic modifications may be the key in explaining how environmental factors modulate and modify gene expression, leading to the dysregulation of immune tolerance and consequently, the development of food allergies. The emerging epigenetic paradigm in food allergies is likely to provide new mechanistic insight into food allergy risk and development as well as shape our therapeutic and preventive strategies. PMID- 26150171 TI - An unprecedented up-field shift in the 13C NMR spectrum of the carboxyl carbons of the lantern-type dinuclear complex TBA[Ru2(O2CCH3)4Cl2] (TBA+ = tetra(n butyl)ammonium cation). AB - A large up-field shift (-763 ppm) has been observed for the carboxyl carbons of the dichlorido complex TBA[Ru(2)(O(2)CCH(3))(4)Cl(2)] (TBA(+) = tetra(n butyl)ammonium cation) in the (13)C NMR spectrum (CD(2)Cl(2) at 25 degrees C). The DFT calculations showed spin delocalization from the paramagnetic Ru(2)(5+) core to the ligands, in agreement with the large up-field shift. PMID- 26150172 TI - [Statins in the secondary prevention of stroke: New evidence from the SPARCL Study]. AB - Until recently there was little evidence that statin therapy reduced the risk of stroke recurrence. The SPARCL trial, published in 2006, was the first trial to show the benefits of statin therapy in preventing recurrent stroke. The SPARCL trial showed that treatment with atorvastatin 80mg/day reduced recurrent stroke in patients with a recent stroke or transient ischemic attack (TIA). Several post hoc analyses of different subgroups followed the SPARCL trial. They have not revealed any significant differences when patients were grouped by age, sex or type of stroke. The SPARCL trial has also helped to identify patients who may have a greater benefit from statins: Patients with carotid stenosis, with more intense lipid lowering, and those who achieve optimal levels of LDL-C, HDL-C, triglycerides, and blood pressure. The trial has also helped to identify individuals at high risk of new vascular events. Clearly there is a before and after in stroke prevention since the SPARCL trial was published. PMID- 26150173 TI - Are Changes in Serum Potassium Levels During Admissions for Acute Decompensated Heart Failure Irrelevant for Prognosis: The End of the Story? PMID- 26150174 TI - Comparison of Brachial Vein Versus Internal Jugular Vein Approach for Access to the Right Side of the Heart With or Without Myocardial Biopsy. AB - Right heart catheterization (RHC) and endomyocardial biopsy are mainstay procedures for patients with heart failure and heart transplantation. Approaches are predominantly neck (internal jugular) or leg (femoral vein). We describe a novel arm (brachial/basilica vein) approach. Over 5.5 years, 1,130 right-sided cardiac procedures in 276 patients were analyzed retrospectively and divided into either neck or arm approach. Comparative analyses of procedural success, time, safety, efficacy, and cost were performed. Patient preference was assessed for those who had both neck and arm approaches. In patients receiving RHC (174 neck and 121 arm cases) and in those receiving RHC + biopsy (594 neck and 141 arm cases), mean elapsed and fluoroscopic times (minutes), respectively, were 60 +/- 20 versus 62 +/- 19 and 3.43 +/- 3.8 versus 4.99 +/- 5.2 (RHC neck vs arm, respectively), and 55 +/- 19 versus 63 +/- 17 and 4.14 +/- 3.4 versus 5.22 +/- 2.6 (RHC + biopsy neck vs arm, respectively). Procedural complications were low (n = 7, 0.6%) and restricted to the neck approach. Patients surveyed preferred the arm approach. In conclusion, RHC and endomyocardial biopsy through the brachial vein can be performed safely, timely, effectively, and at equivalent cost compared with a neck approach. We advocate that an arm approach be the preferred method for these procedures. PMID- 26150175 TI - Factors Associated With and Outcomes After Ventricular Fibrillation Before and During Primary Angioplasty in Patients With ST-Segment Elevation Myocardial Infarction. AB - We aimed to assess the risk factors and outcome of ventricular fibrillation (VF) before and during primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction. From 1999 to 2012, we consecutively enrolled 5,373 patients with ST-segment elevation myocardial infarction. In total, 410 of the patients had VF before and 88 had VF during PPCI. During a mean follow-up of 4.2 years, 1,196 subjects died. A logistic regression model identified younger age, anterior infarct, Killip class >I at admission, and a preprocedural Thrombolysis In Myocardial Infarction flow grade of 0 to I to be significantly associated with VF before PPCI, whereas inferior infarct, a preprocedural Thrombolysis In Myocardial Infarction flow grade of 0 to I, and Killip class >I at admission were significantly associated with VF during PPCI. All-cause mortality was evaluated using the Cox regression model. Compared with the patients without VF, those with VF before or during PPCI had a significantly increased 30-day mortality, with an adjusted hazard ratio = 3.40 (95% confidence interval 1.70 to 6.70) and 4.20 (95% confidence interval 1.30 to 13.30), respectively. Importantly, there was no tendency of 30-day mortality difference between VF before and during PPCI (p = 0.170). In patients with VF before or during PPCI who survived for at least 30 days, there was no increase in the long-term mortality. In conclusion, our data suggest that 30-day mortality is the same for patients with VF before PPCI compared with VF during PPCI, and the occurrence of VF before or during PPCI was associated with increased 30-day mortality but not with long-term mortality. PMID- 26150176 TI - How forgiveness promotes offender pro-relational intentions: The mediating role of offender gratitude. AB - Although relationship restoration is an important outcome of forgiveness, little is known about how forgiveness facilitates such an outcome. In addition, in forgiveness research, little attention is paid to the perspective of the offender. We address these two shortcomings simultaneously, testing the idea that forgiveness promotes offender gratitude, which in turn encourages offender pro relational intentions. Across three experimental studies, participants were induced to believe they had transgressed; recalled a time when they had transgressed; and imagined transgressing. In studies 1 and 2, forgiveness was manipulated; in Study 3, victim motivation for forgiving was manipulated. State gratitude--in comparison with guilt, indebtedness, and positive affect--was consistently found to play the primary mediating role between forgiveness and pro relational intentions. PMID- 26150178 TI - Organotrifluoroborates: Another Branch of the Mighty Oak. AB - Over the past two decades, organotrifluoroborates have evolved from being chemical curiosities to important reagents for the elaboration of organic molecules. Aside from their often-unique reactivity patterns, favorable features of these reagents include their ease of preparation/isolation, reliable crystallinity, enhanced stability, and monomeric structure. Currently >600 structurally diverse reagents of this class are commercially available, and >850 such compounds have been reported from the author's laboratory. The organotrifluoroborates can be utilized as shelf-stable precursors to a variety of end products through simple functional group transformations and have also been employed as partners in cross-coupling reactions between aromatic, alkenyl, alkynyl, and alkyl substrates in library or individual formats. Within the realm of cross-coupling reactions, organotrifluoroborates provide a practical entry to substructural entities not readily accessed using other organometallic reagents, and most recently, the development of a novel mechanistic paradigm for cross coupling promises to expand the range of accessible cross-coupling partners even further to include both single- and two-electron processes. PMID- 26150177 TI - Low expression of dendritic cell-specific intercellular adhesion molecule grabbing nonintegrin-related protein in lung cancer and significant correlations with brain metastasis and natural killer cells. AB - Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin related protein (DC-SIGNR) is a type II transmembrane protein which has been reported to bind a variety of pathogens as well as participate in immunoregulation. But the association between the level of DC-SIGNR and lung cancer is unknown. To investigate the clinical diagnostic significance of DC SIGNR in lung cancer, we investigated serum DC-SIGNR levels in 173 lung cancer patients and 134 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Results showed that serum DC-SIGNR levels in lung cancer patients were lower than that in healthy controls (P = 0.0003). A cut-off value of 3.8998 ng/L for DC-SIGNR predicted the presence of lung cancer with 78.03% sensitivity and 49.25% specificity (area under the curve = 0.6212, P = 0.0003). Strikingly, serum DC-SIGNR levels were significantly higher in lung cancer patients with brain metastasis compared to those without metastasis (P = 0.0283). Moreover, the serum concentrations of DC-SIGNR in lung cancer patients also correlated significantly with serum natural killer cells percentage (P = 0.0017). In addition, immunohistochemistry assay demonstrated that the expression of DC-SIGNR in lung tissues of 31 lung cancer patients and 13 tuberculosis patients was significantly lower than that in 18 normal lung tissues (P = 0.0418, 0.0289), and there is no significant difference between tuberculosis tissues and lung cancer tissues (P = 0.2696). These results suggest that DC-SIGNR maybe a promising biological molecule that has the potential for clinical research of lung cancer, whereas its underlying roles are needed to be investigated in further studies. PMID- 26150179 TI - Sternal Segment Dislocation in a Child Treated by Conservative Observation. AB - Sternal segment dislocation is rare in children, with only eight cases appearing in the literature. Four of the six reports recommended surgical treatment such as excision or open reduction and fixation [1-4], while the remaining two reports recommended conservative observation. Therefore, it remains unclear whether surgical treatment is necessary. We report a case of sternal segment dislocation in a child. Although the segment had rotated 90 degrees , it was remodeled. We now believe that surgical treatment is not necessary for this condition. PMID- 26150180 TI - Cytological Study of Grade 3 Endometrioid Adenocarcinoma of Endometrial Origin: Cytoarchitecture and Features of Cell Clusters Assessed With Endometrial Brushing Cytology--Focusing on a comparison with endometrioid adenocarcinoma Grade 1, 2. AB - OBJECTIVES: Aim of study was to clarify the cytological characteristics of grade 3 endometrioid adenocarcinoma of endometrial origin (G3 EA) by endometrial brushing cytology. METHODS: The subjects were 11 patients in whom G3 EA was diagnosed by review of preoperative cytological specimens obtained at our hospital and related institutions between 2000 and 2010. These patients were investigated with respect to the preoperative cytological diagnosis, background changes, cell cluster patterns, and individual cellular findings. Background changes were classified as inflammatory or tumorous, while cell clusters were classified as overlapping cell cluster, sheet-like cell cluster, clump of high dense gland, papillary, or other cell cluster. Cellular findings were investigated by comparing the incidence of squamous and clear cell metaplasia, the nuclear rounding rate, and the nuclear area with the findings in a control group (35 patients with G1-2 EA). RESULTS: Background changes were classified as inflammatory in 63.6% and necrotic in 36.4%. The cell clusters were classified as overlapping cell cluster in 44.8%, cell cluster in 21.7%, clump of high dense gland in 10.0%, papillary in 4.0%, and other cell cluster in 19.5%. The incidence of squamous and clear cell metaplasia was 27.2% and 18.1%, respectively. The mean nuclear rounding rate was 0.97, and the mean nuclear area was 55.98 um2. CONCLUSION: Investigation of the cytoarchitecture of G3 EA with endometrial brushing cytology revealed overlapping cell cluster and tumor cells of a relatively uniform size. These findings suggest that it is necessary to recognize that there are differences between the cytological findings of G3 EA and the usual features of G1-2 EA. PMID- 26150181 TI - Small Cell Type of Esophageal Neuroendocrine Carcinoma Resembling a Submucosal Tumor. AB - We report a rare case of primary small cell type esophageal neuroendocrine carcinoma with a unusual endoscopic form similar to a submucosal tumor with the results of the histological and immunohistochemical analyses. A 57-year-old woman with dysphagia was referred to our hospital for further examination and treatment, and was diagnosed as type 1s esophageal carcinoma in the middle thoracic esophagus. Endoscopy revealed a protruding esophageal carcinoma resembling a submucosal tumor with an irregular and nodular surface covered by non-neoplastic epithelium stained with iodine. Analysis of the esophageal biopsy specimen revealed poorly differentiated squamous cell carcinoma. Based on a diagnosis of type 1s carcinoma in the middle thoracic esophagus that was 5 cm in size longitudinally, a radical esophagectomy with three-field lymph node dissection was performed. The pathological examination with histological and immunohistochemical analysis of the resected specimen revealed a small cell type neuroendocrine carcinoma overlaid by a non-neoplastic epithelium, extending into the adventitia without lymph node metastasis (T3, N0, M0, Stage II). However, multiple metastases in the brain and lung developed 3 months postoperatively, and the patient died of the cancer 7 months after the operation. This was a rare case of a highly malignant primary small cell type esophageal neuroendocrine carcinoma showing extremely rare form. PMID- 26150182 TI - Duodenal Emphysema Complicated with Superior Mesenteric Artery Syndrome in a Patient with Cerebral Paralysis: A Case Report. AB - Superior mesenteric artery syndrome (SMAS) is characterized by an arteriomesenteric duodenal compression commonly resulting from significant weight loss. Vomiting is the most frequent symptom. SMAS can be complicated by massive gastric dilatation. Patients with cerebral palsy have various factors that can predispose them to SMAS. In this paper, we report a rare case of SMAS complicated by duodenal, peritoneal and retroperitoneal emphysema in a patient with cerebral paralysis, referring to the relevant literature. In this case, severe vomiting associated with epilepsy and weight loss may have contributed to the development of duodenal emphysema. PMID- 26150183 TI - A Case of a TSH-secreting Pituitary Adenoma Associated with Evans' Syndrome. AB - We present a case of a TSH-secreting pituitary adenoma (TSHoma) associated with Evans' syndrome. A 30-year-old woman was referred to our hospital due to purpura and ecchymoses on her limb and body and epistaxis. Evans' syndrome was diagnosed based on idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. She had a history of malocclusion and thyroid gland enlargement 4 years prior to admission. Endocrinological tests and magnetic resonance imaging also revealed that this patient had hyperthyroidism due to the TSHoma and that this adenoma concomitantly secreted GH. Recently, several cases of Evans' syndrome were associated with hyperthyroidism caused by autoimmune thyroid disease, such as Graves' disease, suggesting that these 2 conditions may have a common immunological basis. To the best of our knowledge, there is no case report of Evans' syndrome associated with hyperthyroidism due to TSHoma. Our report suggests that the excess of thyroid hormone itself promotes autoimmunity in Evans' syndrome. Thus, early treatment for hyperthyroidism is necessary in TSHomas because of the possibility that thyroid hormone normalization may prevent the development of Evans' syndrome. PMID- 26150184 TI - Lopinavir/Ritonavir, an Antiretroviral Drug, Lowers Sperm Quality and Induces Testicular Oxidative Damage in Rats. AB - BACKGROUND: Lopinavir/Ritonavir (Kaletra(r)) is a protease inhibitor used in the management of HIV infection. The increased incidence of toxicity of antiretroviral therapy (ART) has necessitated proper evaluation of their effects on reproductive health. PURPOSE: Therefore, this study was designed to investigate the effects of Kaletra(r) on male reproductive system in Wistar rat. METHODS: Eighteen rats were assigned into three groups. The first group served as control while the second and third groups received Kaletra(r) at therapeutic dose (8.3 mg/kg) (Kaletra-T) and twice therapeutic dose (16.6 mg/kg) (Kaletra-2T). Kaletra(r) was given orally for 21 days. RESULTS: Administration of Kaletra(r) caused a significant (p = 0.023) decrease in body weight-gain of rats. Precisely, Kaletra-T and Kaletra-2T decreased body weight-gain by 43% and 48%, respectively. Kaletra-T and kaletra-2T significantly (p = 0.016-0.036) decreased sperm motility and sperm count while kaletra-2T increased total sperm abnormalities in the rats. Also, Kaletra(r) (at the two doses) caused a significant (p = 0.02-0.04) increase in the levels of testicular lipid peroxidation with a concomitant decrease in antioxidant indices. Specifically, Kaletra-T and Kaletra-2T decreased the activities of glutathione peroxidase by 38% and 57%, catalase by 40% and 48%, glutathione-s-transferase by 32% and 35% and superoxide dismutase by 47% and 52%, respectively while Kaletra-2T decreased reduced glutathione by 49%. Photomicrographs of testis from control and Kaletra-T groups showed normal seminiferous tubules with abundant spermatogenic cells while Kaletra-2T group had few and abnormal shape spermatogenic cells. CONCLUSION: Kaletra(r) induces oxidative damage in testis of rats leading to changes in sperm characteristics and antioxidant status of the animals. PMID- 26150185 TI - Lip Repair Surgery for Bilateral Cleft Lip and Palate in a Patient Diagnosed with Trisomy 13 and Holoprosencephaly. AB - We report a case of lip repair surgery performed for bilateral cleft lip and palate in a patient diagnosed with trisomy 13 and holoprosencephaly. At the age of 2 years and 7 months, the surgery was performed using a modified De Hann design under general anesthesia. The operation was completed in 1 h and 21 min without large fluctuations in the child's general condition. The precise measurement of the intraoperative design was omitted, and the operation was completed using minimal skin sutures. It is possible to perform less-invasive and short surgical procedures after careful consideration during the preoperative planning. Considering the recent improvements in the life expectancy of patients with trisomy 13, we conclude that surgical treatments for non-life threatening malformations such as cleft lip and palate should be performed for such patients. PMID- 26150186 TI - Small Intestinal Metastasis from Esophageal Squamous Cell Carcinoma Presenting with Perforated Peritonitis. AB - Metastatic tumors of the small intestinal tract from extra-abdominal sites are rare. We report herein a rare case of small intestinal metastasis from esophageal carcinoma that presented with perforated peritonitis. A 71-year-old man with dysphagia was referred to our hospital for further examination and treatment, and was diagnosed with type 3 advanced esophageal squamous cell carcinoma of the lower thoracic esophagus. Based on a diagnosis of Stage II cancer, a radical esophagectomy with three-field lymph node dissection was performed after neoadjuvant chemotherapy composed of 5-fluorouracil plus cisplatin. Pathological examination of the resected specimen revealed a moderately differentiated squamous cell carcinoma, extending into the adventitia with lymph node metastasis (T3, N2, M0, Stage III). During postoperative adjuvant chemotherapy, the patient complained of abdominal pain and was found to have perforated peritonitis. Emergency laparotomy was performed. A jejunal perforation with a submucosal nodule approximately 80 cm distal from the ligament of Treitz was detected, and completely resected by jejunal partial resection. Histopathology of the specimen showed a perforation of the small intestine due to metastasis of esophageal squamous cell carcinoma with mesenteric lymph node metastasis. The patient died of cancer 9 months after surgery. An extremely rare case of small intestinal metastasis from esophageal carcinoma presenting with perforated peritonitis was described. PMID- 26150187 TI - The Diagnosis of Sick House Syndrome: the Contribution of Diagnostic Criteria and Determination of Chemicals in an Indoor Environment. AB - OBJECTIVE: The study group for sick house syndrome (SHS) in Japan has proposed the classifications, definition and diagnostic criteria for chemical-associated SHS. We compared the physicians' diagnoses to the diagnoses based on the patients' interview sheets including diagnostic criteria only. METHODS: We examined 287 patients with complaints of SHS-like symptoms. We also checked determinations of chemical substances in the patients' homes. RESULTS: A total of 76.0% of the patients were diagnosed as having SHS. Physicians diagnosed 87.6% of those patients as having chemical-associated SHS based on SHS classifications, definition and diagnostic criteria. Based on the patients' interview sheets, 50.3% of the patients who were diagnosed as chemical-associated SHS corresponded to the diagnostic criteria. The 51 of those chemical-associated SHS patients had answered that the chemical substance levels in their homes had been checked, and 20 of those patients answered that at least one of the chemical substance levels was above that set in the guideline by the Japanese Ministry of Health, Labour and Welfare. CONCLUSIONS: Physicians should use all of the classifications, definition and diagnostic criteria. Even if the chemical levels in the home are under the guideline levels, the diagnosis of chemical-associated SHS should not be excluded. PMID- 26150188 TI - Cranial Reconstruction in a Pediatric Patient Using a Tissue Expander and Custom made Hydroxyapatite Implant. AB - A tissue expansion technique in conjunction with a custom-made artificial bone implant was effective for a large cranial reconstruction in a pediatric patient. The patient was an eight-year-old boy with cranial bone fracture, acute subdural hematoma in the left lobe, and acute epidural hematoma in the right lobe due to an accident. Wound dehiscence and artificial dura infection were observed as postoperative complications. Because of insufficiency of the skin flap caused by scar contracture, a scalp skin expansion using a tissue expander was necessary before reconstruction with the artificial bone implant. This combined procedure provided safe coverage of the implant and resulted in good wound healing. There are relatively few reports involving the use of tissue expanders for cranioplasty; furthermore, our search of the literature did not reveal any reports involving children. We believe that this procedure is safe and effective for early rehabilitation in pediatric patients. PMID- 26150189 TI - Chondrogenic capability of osteoarthritic chondrocytes from the trapeziometacarpal and hip joints. AB - Osteoarthritis is the most common degenerative disease of joints like the hip and the trapeziometacarpal joint (rhizarthrosis). In this in vitro study, we compared the chondrogenesis of chondrocytes derived from the trapezium and the femoral head cartilage of osteoarthritic patients to have a deeper insight on trapezium chondrocyte behavior as autologous cell source for the repair of cartilage lesions in rhizarthrosis. Chondrocytes collected from trapezium and femoral head articular cartilage were cultured in pellets and analyzed for chondrogenic differentiation, cell proliferation, glycosaminoglycan production, gene expression of chondrogenic and fibrous markers, histological and immunohistochemical analyses. Our results showed a higher cartilaginous matrix deposition and a lower fibrocartilaginous phenotype of the femoral chondrocytes with respect to the trapezium chondrocytes assessed by a higher absolute glycosaminoglycan and type II collagen production, thus demonstrating a superior chondrogenic potential of the femoral with respect to the trapezium chondrocytes. The differences in chondrogenic potential between trapezium and femoral head chondrocytes confirmed a lower regenerative capability in the trapezium than in the femoral head cartilage due to the different environment and loading acting on these joints that affects the metabolism of the resident cells. This could represent a limitation to apply the cell therapy for rhizoarthrosis. PMID- 26150190 TI - Comparison between cryopreserved and glycerol-preserved allografts in a partial thickness porcine wound model. AB - Human skin allografts are one of the best temporary biological coverings for severely burned patients. Cryopreserved (CPA) and glycerol-preserved (GPA) allografts are the most widely used types. This study compared the allograft efficiency of both preservation methods under the same conditions. To simulate actual clinical conditions, we used a porcine wound model. In addition, we evaluated the macroscopic and microscopic scoring of graft performance for each method. Porcine cadaver skin 1 mm thick was obtained from one pig. Cryopreserved skin cell viability was 20.8 %, glycerol-preserved skin was 9.08 %, and fresh skin was 58.6 %. We made ten partial-thickness wounds each in two pigs. The take rates on day 2 were 96.23 and 82.65 % in the GPA and CPA group (both n = 9), respectively. After 1 week, the take rates of both groups were nearly equal. The removal rate at week 5 was 98.87 and 94.41 % in the GPA and CPA group, respectively. On microscopic findings at week 2, inflammation was greater in the CPA group. Other findings such as fibroblast hyperplasia and neovascularization were not significantly different between both groups. At week 5, the score of collagen fiber synthesis was 2.67 +/- 0.47 and 2.33 +/- 0.47 in the GPA and CPA group, respectively. The epidermal-dermal junction was 2.22 +/- 0.79 and 2.00 +/- 0.47 in the GPA and CPA group, respectively. These findings suggest that wound healing takes longer in the CPA group. The preservation method of allografts is not a absolute factor in the wound healing process in this wound model. PMID- 26150191 TI - Different flavors of Toll guide olfaction. AB - Toll-like receptors are historically linked to immunity across animal phyla, but accumulating evidence suggests they play additional roles in neuronal networks and in cell-cell interactions. Ward and colleagues now identify Toll-6 and Toll-7 as instructive guidance cues during Drosophila olfactory development. PMID- 26150192 TI - The relationship between vitamin D status and cardiac autonomic neuropathy in patients with type 2 diabetes mellitus. AB - OBJECTIVE: This study evaluates cardiac autonomic neuropathy and heart rate variability according to the vitamin D status in type 2 diabetes mellitus. METHODS: A total of 163 patients were recruited. Cardiac autonomic neuropathy was assessed using five tests according to Ewing's protocol. The time and frequency domains of the heart rate variability were also evaluated. Patients were separated into three groups: vitamin D sufficient [25(OH)D ? 20 ng/mL], vitamin D insufficient [10 ? 25(OH)D < 20] and vitamin D deficiency [25(OH)D < 10] groups. RESULTS: Both standard deviation of normal-to-normal RR intervals and square root of the average of the sum of the squares of the differences between adjacent NN intervals in the supine position were significantly lower in vitamin D deficient group. Low frequency/high frequency ratio in the upright position was significantly higher in the vitamin D deficient group. 25(OH)D levels are positively correlated with standard deviation of normal-to-normal RR intervals in the supine position. In multivariate logistic analysis, patients with vitamin D levels of 10 < 25(OH)D < 20 ng/mL showed borderline significantly lower cardiac autonomic neuropathy risk than those with 25(OH)D levels <10 ng/mL (odds ratio = 0.45 (0.23-1.01), p = 0.051). CONCLUSION: Vitamin D deficiency was significantly correlated with heart rate variability parameters. However, there was only borderline significant association between vitamin D concentration and presence of cardiac autonomic neuropathy. Therefore, future studies are required to establish a relationship between vitamin D levels and cardiac autonomic neuropathy. PMID- 26150193 TI - Impact of diabetes on the benefits from everolimus-eluting stent as compared to first-generation drug-eluting stent in patients with ST elevation myocardial infarction. AB - BACKGROUND: Drug-eluting stent has been shown to reduce the risk of repeated revascularization. However, as shown for first-generation drug-eluting stent, they may be counterbalanced by a potential higher risk of stent thrombosis, especially among ST-segment elevation myocardial infarction patients. In addition, diabetes has been shown to be an independent predictor of poor survival and repeated target vessel revascularization. No data have been reported so far on the long-term benefits and safety of new-generation drug-eluting stent in ST segment elevation myocardial infarction according to diabetes. Therefore, the aim of this study was to evaluate whether diabetes may impact on the benefits from everolimus-eluting stent versus first-generation drug-eluting stent in patients undergoing primary angioplasty. METHODS: We combined data from two randomized trials (PaclitAxel or Sirolimus-Eluting Stent vs Bare-Metal Stent in Primary Angioplasty and randomized comparison of everolimus-eluting stents and sirolimus eluting stents in patients with ST elevation myocardial infarction) including consecutive ST-segment elevation myocardial infarction patients admitted within 12 h of symptom onset undergoing primary angioplasty and stent implantation at a tertiary centre with 24-h primary percutaneous coronary intervention capability. Primary endpoint of this study was major adverse cardiac events at 3-year follow up. Secondary endpoints were as follows: (1) death, (2) reinfarction, (3) definite or probable ST and (4) target vessel revascularization at 3-year follow up. No patient was lost to follow-up. RESULTS: Our population is represented by 680 ST-segment elevation myocardial infarction patients treated with drug-eluting stent (180 enrolled in the PaclitAxel or Sirolimus-Eluting Stent vs Bare-Metal Stent in Primary Angioplasty trial, treated with first-generation drug-eluting stent, and 500 patients in the randomized comparison of everolimus-eluting stents and sirolimus-eluting stents in patients with ST elevation myocardial infarction, randomized to everolimus-eluting stent or sirolimus-eluting stent). Diabetes was observed in a total of 178 patients (26.1%) and associated with higher major adverse cardiac events, mortality, reinfarction, stent thrombosis and target vessel revascularization. Similar outcome was observed in terms of overall major adverse cardiac events, mortality, recurrent myocardial infarction, target vessel revascularization, with everolimus-eluting stent as compared to first-generation drug-eluting stent in both diabetic and non-diabetic patients, whereas everolimus eluting stent was associated with a significantly lower rate of stent thrombosis only in diabetic patients (1.6% vs 9.6%, hazard ratio (95% confidence interval) = 0.15 (0.02-0.98), p = 0.04) whereas no difference was observed in non-diabetic patients. CONCLUSION: This study shows that among ST-segment elevation myocardial infarction patients undergoing primary angioplasty, diabetes is associated with a significantly worse outcome at 3-year follow-up. A similar outcome was observed between everolimus-eluting stent and first-generation drug-eluting stent in non diabetic patients, whereas among diabetic patients everolimus-eluting stent was associated with a significant reduction in stent thrombosis. PMID- 26150195 TI - A novel cyclophilin gene from the dinoflagellate Prorocentrum minimum and its possible role in the environmental stress response. AB - Cyclophilins (CYPs) are a family of proteins that bind to cyclosporine and are thought to be involved in the stress response. In dinoflagellate algae, CYPs may function as a survival strategy in cells exposed to environmental stressors. Here, we identified a novel cyclophilin gene (referred to as PmCYP, comprising a 516-bp open reading frame, encoding a 171-aa protein with a molecular mass of 17.5kDa) from the dinoflagellate Prorocentrum minimum, and evaluated the role of dinoflagellate CYP in cells exposed to environmental pollutants copper and polychlorinated biphenyl. In addition, we assessed the cytoprotective role of nitric oxide in relation to the expression of PmCYP. These stressors strongly affected the physiology of the cells, as judged by cell counting, reactive oxygen species (ROS) imaging, and photosynthetic parameters (Fv/Fm and PIABS). PmCYP expression was significantly (P<0.05) induced upon exposure of the cells to all the test pollutants used in this study. These clearly indicate that PmCYP plays a vital role in the oxidative stress response in dinoflagellate survival, although the gene was initially known only for its housekeeping function. PMID- 26150196 TI - Screening procedure for airborne pollutants emitted from a high-tech industrial complex in Taiwan. AB - Despite the modernization of computational techniques, atmospheric dispersion modeling remains a complicated task as it involves the use of large amounts of interrelated data with wide variability. The continuously growing list of regulated air pollutants also increases the difficulty of this task. To address these challenges, this study aimed to develop a screening procedure for a long term exposure scenario by generating a site-specific lookup table of hourly averaged dispersion factors (chi/Q), which could be evaluated by downwind distance, direction, and effective plume height only. To allow for such simplification, the average plume rise was weighted with the frequency distribution of meteorological data so that the prediction of chi/Q could be decoupled from the meteorological data. To illustrate this procedure, 20 receptors around a high-tech complex in Taiwan were selected. Five consecutive years of hourly meteorological data were acquired to generate a lookup table of chi/Q, as well as two regression formulas of plume rise as functions of downwind distance, buoyancy flux, and stack height. To calculate the concentrations for the selected receptors, a six-step Excel algorithm was programmed with four years of emission records and 10 most critical toxics were screened out. A validation check using Industrial Source Complex (ISC3) model with the same meteorological and emission data showed an acceptable overestimate of 6.7% in the average concentration of 10 nearby receptors. The procedure proposed in this study allows practical and focused emission management for a large industrial complex and can therefore be integrated into an air quality decision-making system. PMID- 26150194 TI - MRI of High-Glucose Metabolism Tumors: a Study in Cells and Mice with 2-DG Modified Superparamagnetic Iron Oxide Nanoparticles. AB - PURPOSE: This study aims to evaluate the effect of dimercaptosuccinic acid (DMSA) coated superparamagnetic iron oxide (gamma-Fe(2)O(3)@DMSA) bearing the 2-deoxy-D glucose (2-DG) ligand on targeting tumors with high-glucose metabolism. PROCEDURES: gamma-Fe(2)O(3)@DMSA and 2-DG-conjugated gamma-Fe(2)O(3)@DMSA (gamma Fe(2)O(3)@DMSA-DG) were prepared. The glucose consumption of MDA-MB-231 and MCF-7 breast cancer cells and human mammary epithelial cells (HMEpiCs) was assessed. Cells were incubated with gamma-Fe(2)O(3)@DMSA or gamma-Fe(2)O(3)@DMSA-DG, and MDA-MB-231 cells which exhibited the highest glucose consumption were used in breast cancer xenografts. Tumor targeting was studied by magnetic resonance imaging and Prussian blue staining in vivo. RESULTS: Glucose consumption was highest in MDA-MB-231 and lowest in HMEpiCs. In vitro, there was significant uptake of gamma-Fe(2)O(3)@DMSA-DG by MDA-MB-231 and MCF-7 cells within 2 h and this was inhibited by glucose. Uptake of gamma-Fe(2)O(3)@DMSA-DG was significantly higher in MDA-MB-231 compared with MCF-7 cells, and there was no obvious uptake of gamma-Fe(2)O(3)@DMSA in either cell line. In vivo, gamma Fe(2)O(3)@DMSA-DG could be detected in the liver and in tumors post-injection, while gamma-Fe(2)O(3)@DMSA was nearly undetectable in tumors. CONCLUSIONS: 2-DG coated gamma-Fe(2)O(3)@DMSA improved tumor targeting of gamma-Fe(2)O(3)@DMSA which can be assessed by magnetic resonance imaging. PMID- 26150197 TI - Scented traces--Dermal exposure of synthetic musk fragrances in personal care products and environmental input assessment. AB - Synthetic musks are organic compounds used as fragrance and fixative additives in several personal care products. Until now, little is known about their occurrence and distribution in these household commodities. However, this information is essential to perform a human dermal exposure assessment. Therefore, this study gives an overview on the levels of 12 synthetic musks in 140 personal care products from 7 different categories (body and hair wash, toilet soaps, shaving products, dentifrice products, deodorants/antiperspirants, moisturizers and perfumes). They were analysed by QuEChERS extraction followed by gas chromatography-mass spectrometry. Detection limits were found between 0.01ngg(-1) (galaxolide) and 5.00ngg(-1) (musk xylene). Higher average concentrations of total synthetic musks were detected in perfumes (5245.05MUgg(-1)) and shampoos (487.67MUgg(-1)) for adults. Galaxolide, exaltolide and cashmeran were the most detected compounds. Combining these results with the daily usage amounts, an average daily dermal exposure of 75.69MUgkgbw(-1)day(-1) for adults and 15.54MUgkgbw(-1)day(-1) for babies/children was achieved. The main contributors for adult and babies/children dermal exposure were perfumes and lotions, respectively. About 40% of the adult daily dermal exposure is related to exaltolide, 30% galaxolide, and 15% tonalide, while for babies/children 96% occurs due to exaltolide. An estimate of the amount of musks discharged "down-the drain" into the wastewater treatment systems through the use of toiletries was also performed. An average emission per capita of 6.7mgday(-1) was determined and galaxolide and exaltolide were the predominant musks in the effluents. PMID- 26150198 TI - Exposure to, and searching for, information about suicide and self-harm on the Internet: Prevalence and predictors in a population based cohort of young adults. AB - BACKGROUND: There is concern over the potential impact of the Internet on self harm and suicidal behaviour, particularly in young people. However, little is known about the prevalence and patterns of suicide/self-harm related Internet use in the general population. METHODS: Cross sectional study of 3946 of the 8525 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) who were sent a self-report questionnaire including questions on suicide/self-harm related Internet use and self-harm history at age 21 years. RESULTS: Suicide/self harm related Internet use was reported by 22.5% (886/3946) of participants; 11.9% (470/3946) had come across sites/chatrooms discussing self-harm or suicide, 8.2% (323/3946) had searched for information about self-harm, 7.5% (296/3946) had searched for information about suicide and 9.1% (357/3946) had used the Internet to discuss self-harm or suicidal feelings. Suicide/self-harm related Internet use was particularly prevalent amongst those who had harmed with suicidal intent (70%, 174/248), and was strongly associated with the presence of suicidal thoughts, suicidal plans, and history of self-harm. Sites offering help, advice, or support were accessed by a larger proportion of the sample (8.2%, 323/3946) than sites offering information on how to hurt or kill yourself (3.1%, 123/3946). Most individuals (81%) who had accessed these potentially harmful sites had also accessed help sites. LIMITATIONS: (i) There were differences between questionnaire responders and non-responders which could lead to selection bias and (ii) the data were cross-sectional, and we cannot conclude that associations are causal. CONCLUSIONS: Suicide/self-harm related Internet use is common amongst young adults, particularly amongst those with suicidal thoughts and behaviour. Both harmful and helpful sites were accessed, highlighting that the Internet presents potential risks but also offers opportunities for suicide prevention. PMID- 26150199 TI - Change of function of the wheat stress-responsive transcriptional repressor TaRAP2.1L by repressor motif modification. AB - Plants respond to abiotic stresses by changes in gene regulation, including stress-inducible expression of transcriptional activators and repressors. One of the best characterized families of drought-related transcription factors are dehydration-responsive element binding (DREB) proteins, known as C-repeat binding factors (CBF). The wheat DREB/CBF gene TaRAP2.1L was isolated from drought affected tissues using a dehydration-responsive element (DRE) as bait in a yeast one-hybrid screen. TaRAP2.1L is induced by elevated abscisic acid, drought and cold. A C-terminal ethylene responsive factor-associated amphiphilic repression (EAR) motif, known to be responsible for active repression of target genes, was identified in the TaRAP2.1L protein. It was found that TaRAP2.1L has a unique selectivity of DNA-binding, which differs from that of DREB activators. This binding selectivity remains unchanged in a TaRAP2.1L variant with an inactivated EAR motif (TaRAP2.1Lmut). To study the role of the TaRAP2.1L repressor activity associated with the EAR motif in planta, transgenic wheat overexpressing native or mutated TaRAP2.1L was generated. Overexpression of TaRAP2.1L under constitutive and stress-inducible promoters in transgenic wheat and barley led to dwarfism and decreased frost tolerance. By contrast, constitutive overexpression of the TaRAP2.1Lmut gene had little or no negative influence on wheat development or grain yield. Transgenic lines with the TaRAP2.1Lmut transgene had an enhanced ability to survive frost and drought. The improved stress tolerance is attributed to up-regulation of several stress-related genes known to be downstream genes of DREB/CBF activators. PMID- 26150201 TI - Insight into photofragment vector correlation by a multi-center impulsive model. AB - A multi-center impulsive model has been recently developed to characterize the dynamic feature of product energy distribution in photodissociation of formaldehyde, H2CO -> CO + H2. (J. Phys. Chem. A, 2015, 119, 29) The model is extended to predict the vector correlations among transition dipole moment MU of the parent molecule, recoil velocity v and rotational angular momentum j of the fragments produced via the transition state (TS) and roaming path. The correlation results of MU-j, j-j and MU-v vectors of the fragments are consistent with those reported using quasi-classical trajectory simulation on the global potential energy surface. In contrast to the TS route, the vector properties via the roaming path are loosely correlated. This work offers an alternative method to study stereodynamics of the photodissociation process, and is conducive to clarifying the origin of photofragment vector correlation especially for the roaming pathway. PMID- 26150200 TI - Out-of-pocket expenses incurred by patients obtaining free breast cancer care in Haiti: A pilot study. AB - BACKGROUND: Women in low- and middle-income countries account for 51% of breast cancer cases globally. These patients often delay seeking care and, therefore, present with advanced disease, partly because of fear of catastrophic health care expenses. Although there have been efforts to make health care affordable in low- and middle-income countries, the financial burden of out-of-pocket (OOP) expenses for nonmedical costs, such as transportation and lost wages, often is overlooked. METHODS: An institutional review board exemption was granted from Boston Children's Hospital and Partners in Health/Zanmi Lasante for this cross-sectional study. In total, 61 patients receiving breast cancer care free of charge at Hopital Universitaire de Mirebalais (HUM) in Haiti were selected via convenience sampling. They were interviewed between March and May 2014 to quantify the expenses they incurred during the course of diagnosis and treatment. These expenses included medical costs at outside facilities, as well as nonmedical costs (eg, transportation, meals, etc). RESULTS: The median, nonmedical OOP expenses incurred by breast cancer patients at HUM were $233 (95% confidence interval [95% CI] $170-304) for diagnostic visits, $259 (95% CI $200-533) for chemotherapy visits, and $38 (95% CI $23-140) for surgery visits. The median total OOP expense (including medical costs) was $717 (95% CI $619-1,171). To pay for these expenses, 52% of participants stated that they went into debt; however, the amount of debt was not quantified. The median income of these patients was $1,333 (95% CI $778-2,640), and the median sum of OOP expenses and lost wages was $2,996 (95% CI $1,676-5,179). CONCLUSION: Despite receiving free care: at HUM, more than two-thirds of participants met conservative criteria for catastrophic medical expenses (defined as spending more than 40% of their potential household income on OOP payments). Further studies are needed to understand the magnitude of OOP health care expenses for the poor worldwide, how to aid them during their treatment program, and its impact on their health outcomes. PMID- 26150202 TI - Maskless Lithography and in situ Visualization of Conductivity of Graphene using Helium Ion Microscopy. AB - The remarkable mechanical and electronic properties of graphene make it an ideal candidate for next generation nanoelectronics. With the recent development of commercial-level single-crystal graphene layers, the potential for manufacturing household graphene-based devices has improved, but significant challenges still remain with regards to patterning the graphene into devices. In the case of graphene supported on a substrate, traditional nanofabrication techniques such as e-beam lithography (EBL) are often used in fabricating graphene nanoribbons but the multi-step processes they require can result in contamination of the graphene with resists and solvents. In this letter, we report the utility of scanning helium ion lithography for fabricating functional graphene nanoconductors that are supported directly on a silicon dioxide layer, and we measure the minimum feature size achievable due to limitations imposed by thermal fluctuations and ion scattering during the milling process. Further we demonstrate that ion beams, due to their positive charging nature, may be used to observe and test the conductivity of graphene-based nanoelectronic devices in situ. PMID- 26150204 TI - Individual differences in verbal creative thinking are reflected in the precuneus. AB - There have been many structural and functional imaging studies of creative thinking, but combining structural and functional magnetic resonance imaging (MRI) investigations with respect to creative thinking is still lacking. Thus, the aim of the present study was to explore the associations among inter individual verbal creative thinking and both regional homogeneity and cortical morphology of the brain surface. We related the local functional homogeneity of spontaneous brain activity to verbal creative thinking and its dimensions- fluency, originality, and flexibility--by examining these inter-individual differences in a large sample of 268 healthy college students. Results revealed that people with high verbal creative ability and high scores for the three dimensions of creativity exhibited lower regional functional homogeneity in the right precuneus. Both cortical volume and thickness of the right precuneus were positively associated with individual verbal creativity and its dimensions. Moreover, originality was negatively correlated with functional homogeneity in the left superior frontal gyrus and positively correlated with functional homogeneity in the right occipito-temporal gyrus. In contrast, flexibility was positively correlated with functional homogeneity in the left superior and middle occipital gyrus. These findings provide additional evidence of a link between verbal creative thinking and brain structure in the right precuneus--a region involved in internally--focused attention and effective semantic retrieval-and further suggest that local functional homogeneity of verbal creative thinking has neurobiological relevance that is likely based on anatomical substrates. PMID- 26150203 TI - Tolerance to ischaemic injury in remodelled mouse hearts: less ischaemic glycogenolysis and preserved metabolic efficiency. AB - AIMS: Post-infarction remodelled failing hearts have reduced metabolic efficiency. Paradoxically, they have increased tolerance to further ischaemic injury. This study was designed to investigate the metabolic mechanisms that may contribute to this phenomenon and to examine the relationship between ischaemic tolerance and metabolic efficiency during post-ischaemic reperfusion. METHODS AND RESULTS: Male C57BL/6 mice were subjected to coronary artery ligation (CAL) or SHAM surgery. After 4 weeks, in vivo mechanical function was assessed by echocardiography, and then isolated working hearts were perfused in this sequence: 45 min aerobic, 15 min global no-flow ischaemia, and 30 min aerobic reperfusion. Left ventricular (LV) function, metabolic rates, and metabolic efficiency were measured. Relative to SHAM, both in vivo and in vitro CAL hearts had depressed cardiac function under aerobic conditions (45 and 36%, respectively), but they had a greater recovery of LV function during post ischaemic reperfusion (67 vs. 49%, P < 0.05). While metabolic efficiency (LV work per ATP produced) was 50% lower during reperfusion of SHAM hearts, metabolic efficiency in CAL hearts did not decrease. During ischaemia, glycogenolysis was 28% lower in CAL hearts, indicative of lower ischaemic proton production. There were no differences in mitochondrial abundance, calcium handling proteins, or key metabolic enzymes. CONCLUSION: Compared with SHAM, remodelled CAL hearts are more tolerant to ischaemic injury and undergo no further deterioration of metabolic efficiency during reperfusion. Less glycogen utilization in CAL hearts during ischaemia may contribute to increased ischaemic tolerance by limiting ischaemic proton production that may improve ion homeostasis during early reperfusion. PMID- 26150205 TI - Beyond words: Pragmatic inference in behavioral variant of frontotemporal degeneration. AB - When the message of a speaker goes beyond the literal or logical meaning of the sentences used, a pragmatic inference is required to understand the complete meaning of an utterance. Here we study one example of pragmatic inference, called scalar implicature. Such an inference is required when a weaker term "some" is used in a sentence like "Some of the students passed the exam" because the speaker presumably had a reason not to use a stronger term like "all". We investigated the comprehension of scalar implicatures in a group of 17 non aphasic patients with behavioral variant frontotemporal degeneration (bvFTD) in order to test the contribution of non-linguistic decision-making ability and the role of prefrontal cortex in supporting the computation of pragmatic inferences. The results of two experiments point to a deficit in producing alternative interpretations beyond a logical reading. bvFTD patients thus prefer the narrowly literal or logical interpretation of a scalar term when they must generate a possible alternative interpretation by themselves, but patients prefer a pragmatic reading when offered a choice between the logical and the pragmatic interpretation of the same sentence. An imaging analysis links bvFTD patients' spontaneous tendency toward a narrowly logical interpretation with atrophy in ventromedial prefrontal cortex. Our findings are consistent with the pragmatic tolerance hypothesis, which proposes that difficulty generating alternative interpretations of an utterance, rather than a frank inability to compute an inference, affects the comprehension of a scalar term. PMID- 26150207 TI - Tertiary syphilis and Kaposi sarcoma mistaken for systemic sarcoidosis in an HIV negative patient. AB - We describe a case of an HIV-negative man who was mistakenly diagnosed as having systemic sarcoidosis, which led to a delay in diagnosing tertiary syphilis and Kaposi sarcoma (KS). The patient presented initially with scrotal swelling and leg oedema. Initial blood tests were unremarkable and HIV testing was negative. The patient then developed unilateral limb weakness. Computed tomography showed lung lesions and hilar lymphadenopathy, while magnetic resonance imaging showed an increased signal in the cervical cord. Serum angiotensin-converting enzyme was raised, and a diagnosis of sarcoidosis was made and the patient started on steroids. Subsequently, his clinical symptoms and radiological abnormalities improved. However, he then developed progressive neurological deficits over several weeks, together with uveitis and cutaneous lesions. A uveitis screen showed a raised venereal disease research laboratory test titre and the cause of his multisystemic symptoms was revisited. He was diagnosed with tertiary syphilis and treated with antibiotics. Dermatologists reviewed the skin lesions and diagnosed KS, which was confirmed with biopsies. The patient's neurological deficit remains. Syphilis should be considered in the differential diagnosis of any patient presenting with neurological problems, skin lesions or symptoms affecting multiple systems. Co-existing KS presented an extra therapeutic challenge in this case. PMID- 26150206 TI - Progressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate. AB - Progressive multifocal leukoencephalopathy (PML) has recently been described in psoriasis or multiple sclerosis patients treated with fumaric acid esters (fumarates), who had developed severe and long-standing lymphocytopenia (<500/mm(3) ). We report a psoriasis patient who presented with progressive neurologic dysfunction and seizures after 2.5 years of fumarate therapy. Despite absolute lymphocyte counts remaining between 500-1000/mm(3) , his CD4(+) and CD8(+) T-cell counts were markedly low. MRI showed right hemispheric and brainstem lesions and JC virus DNA was undetectable in his cerebrospinal fluid. Brain biopsy revealed typical features of PML as well as JC virus-infected neurons. Clinicians should consider PML in the differential diagnosis of fumarate treated patients presenting with brain lesions or seizures even in the absence of severe lymphocytopenia. PMID- 26150208 TI - Sceptridium ternatum attenuates allergic contact dermatitis-like skin lesions by inhibiting T helper 2-type immune responses and inflammatory responses in a mouse model. AB - BACKGROUND: Sceptridium ternatum (ST) is a medicinal herb used in folk remedies for the treatment of various disorders such as pertussis, allergic asthma, abdominalgia, diarrhea, and external use for wound healing. However, the biological and pharmacological activities of ST are not fully clarified besides anti-asthmatic effect. OBJECTIVE: We studied a Sceptridium ternatum ethanol extract (ST) with respect to its anti-inflammatory and immune regulatory activities in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, concanavalin A (conA)-stimulated BALB/c mice splenocytes, and a 2,4-dinitrochlorobenzene (DNCB) induced allergic contact dermatitis (ACD) mouse model. METHODS: RAW 264.7 cells were pretreated with ST for 1h and then stimulated with LPS. To determine the anti-inflammatory effects of ST, the production of nitric oxide (NO), interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured using an enzyme-linked immunosorbent assay (ELISA). To determine its anti-allergic effects, splenocytes from BALB/c mice were incubated and stimulated with conA in the absence or presence of ST for 48h. The production of IL-4 and interferon (IFN)-gamma in culture supernatants were evaluated by ELISA. To test the effects of ST on ACD, 100MUL of 1% DNCB was applied to the dorsal skin of BALB/c mice for 2 weeks, and ST was administered 2 h before DNCB application. The thicknesses of the epidermis and dermis were determined by skin histological analysis. Serum immunoglobulin (Ig) E levels, the production of IL-1beta, IL-4, and IL-6 in dorsal skin tissue, and T helper (Th) 2 cytokines production of CD4(+) T cells were analyzed by ELISA. The expression of nuclear transcription factor-kappaB (NF kappaB) both in vitro and in vivo was determined via immunoblotting. RESULTS: In RAW 264.7 cells, ST inhibited LPS-induced inflammation mediator production and NF kappaB expression. ST upregulated IFN-gamma production and downregulated IL-4 production in conA-stimulated splenocytes. ST application reduced the thicknesses of the epidermis and dermis by decreasing serum IgE level and the expressions of IL-1beta, IL-4, IL-6, and NF-kappaB in the dorsal skin of the DNCB-induced ACD model mice. Furthermore, ST treated group showed reduction of the Th2 cytokines production in activated CD4(+) T cells. CONCLUSION: These findings not only indicate that application of ST reduced skin thickening by regulating Th 2-type allergic responses and inhibiting expression of inflammatory mediators in a DNCB induced ACD mouse model, but also suggest that Sceptridium ternatum is a natural option for the treatment of skin inflammation. PMID- 26150209 TI - Treatment technologies and mechanisms for three odorants at trace level: IPMP, IBMP, and TCA. AB - Odour episodes caused by algal metabolites are gaining more and more attention in recent years. Besides geosmin and 2-methylisoborneol (MIB), 2-isopropyl-3 methoxypyrazine (IPMP), 2-isobutyl-3-methoxypyrazine (IBMP), and 2,4,6 trichloroanisole (TCA) have emerged to be important off-flavour sources. Their low odour threshold concentrations (several ng .L(-1)), which are even lower than those of MIB and geosmin, pose challenges for treatment strategies. Hence, a practical and efficient mitigation technology is needed. The possible practical technologies, including powdered activated carbon (PAC) adsorption and oxidation by chlorine and potassium permanganate, were investigated. The results indicated that chlorine and potassium permanganate oxidation of the three odorants were unfeasible while PAC adsorption was effective. As for adsorption, TCA, followed by IBMP and IPMP, was most easily removed by PAC. The Freundlich model could well describe the adsorption isotherm data. The adsorption capacities for IPMP, IBMP, and TCA were described as follows: [Formula: see text], [Formula: see text], and [Formula: see text]. For five earthy/musty odorants including geosmin and MIB, octanol/water partition coefficient, molecular weight, and polarizability all promoted adsorption while aqueous solubility showed a negative influence. The hydrophobic interaction was believed to be the dominant force in the adsorption mechanism while the pi-electron interaction enhanced adsorption when a benzene ring was present. This result could be used to predict the adsorption performance of emerging odorants. PMID- 26150210 TI - Protein profiles in mucosal and systemic compartments in response to Vibrio cholerae in a mouse pulmonary infection model. AB - We have recently shown that a mouse lung infection model resulting in acute pneumonia could be used for evaluating the protective immunity induced by mucosal vaccines against Vibrio cholerae. In order to gain insight and better understanding of the pathogenicity of V. cholerae infection, we identified and compared proteins induced by V. cholerae in nasal washes, bronchoalveolar lavages (BAL), and sera. Intranasal administration of V. cholerae increased the concentration of total proteins in nasal washes and BAL fluids, but not in sera. LTQ-Orbitrap hybrid Fourier transform mass spectrometry showed that cytoskeletal proteins, protease inhibitors and anti-inflammatory mediators were present in nasal washes from uninfected mice. The distinctly expressed proteins in nasal washes in response to V. cholerae mainly consisted of protease inhibitors, anti inflammatory proteins, and anti-microbial proteins. A number of protease inhibitors and anti-inflammatory proteins were selectively expressed in BAL fluids from V. cholerae-infected mice, while cytoskeletal proteins and heat shock proteins were mainly observed in BAL fluids from uninfected mice. A large number of serum complements, protease inhibitors, and acute phase proteins were expressed in V. cholerae-infected mice. Collectively, these results suggest that intranasal administration of V. cholerae leading to acute pneumonia elicited alterations of protein profiles associated with immune homeostasis and host protection in both the mucosal and systemic compartments. PMID- 26150211 TI - Xenbase: Core features, data acquisition, and data processing. AB - Xenbase, the Xenopus model organism database (www.xenbase.org), is a cloud-based, web-accessible resource that integrates the diverse genomic and biological data from Xenopus research. Xenopus frogs are one of the major vertebrate animal models used for biomedical research, and Xenbase is the central repository for the enormous amount of data generated using this model tetrapod. The goal of Xenbase is to accelerate discovery by enabling investigators to make novel connections between molecular pathways in Xenopus and human disease. Our relational database and user-friendly interface make these data easy to query and allows investigators to quickly interrogate and link different data types in ways that would otherwise be difficult, time consuming, or impossible. Xenbase also enhances the value of these data through high-quality gene expression curation and data integration, by providing bioinformatics tools optimized for Xenopus experiments, and by linking Xenopus data to other model organisms and to human data. Xenbase draws in data via pipelines that download data, parse the content, and save them into appropriate files and database tables. Furthermore, Xenbase makes these data accessible to the broader biomedical community by continually providing annotated data updates to organizations such as NCBI, UniProtKB, and Ensembl. Here, we describe our bioinformatics, genome-browsing tools, data acquisition and sharing, our community submitted and literature curation pipelines, text-mining support, gene page features, and the curation of gene nomenclature and gene models. PMID- 26150217 TI - Impact versus Significance in scientific publishing. PMID- 26150215 TI - 4(th) European Congress of Immunology - ECI 2015: Vienna, September 6-9, 2015. PMID- 26150212 TI - Protein alterations in women with chronic widespread pain--An explorative proteomic study of the trapezius muscle. AB - Chronic widespread pain (CWP) has a high prevalence in the population and is associated with prominent negative individual and societal consequences. There is no clear consensus concerning the etiology behind CWP although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Here, we use proteomics to study protein changes in trapezius muscle from 18 female patients diagnosed with CWP compared to 19 healthy female subjects. The 2-dimensional gel electrophoresis (2-DE) in combination with multivariate statistical analyses revealed 17 proteins to be differently expressed between the two groups. Proteins were identified by mass spectrometry. Many of the proteins are important enzymes in metabolic pathways like the glycolysis and gluconeogenesis. Other proteins are associated with muscle damage, muscle recovery, stress and inflammation. The altered expressed levels of these proteins suggest abnormalities and metabolic changes in the myalgic trapezius muscle in CWP. Taken together, this study gives further support that peripheral factors may be of importance in maintaining CWP. PMID- 26150220 TI - Clinical analysis of 33 flow-through latissimus dorsi flaps. AB - INTRODUCTION: Indications for flow-through latissimus dorsi (LD) flaps have been limited for reconstructing distal extremities. In addition, there has been little discussion in regard to the question of which branch is most suitable as a distal runoff of the flow-through anastomosis. The aims of this study were to investigate the feasibility of flow-through LD flaps in various areas in the body and the rationale for branch selection for the distal runoff vessel. METHODS: This retrospective study included 33 patients who underwent reconstruction of an oncology-related defect with a free flow-through LD flap. Defect locations, branches used for the distal runoff, and postoperative complications were investigated. RESULTS: The defect location was in the lower extremity in 13 patients, the scalp in seven, the upper extremity in six, the pelvis in six, and the chest in one. In 19 of the 33 patients, the defects were located in areas other than the distal extremities. The circumflex scapular artery (CSA) was most frequently used as the distal runoff vessel (24 patients) followed by the serratus anterior branch (SAB) (five patients). All flaps were transferred successfully without anastomotic failure. CONCLUSIONS: The flow-through LD flap is a reliable option for reconstruction in many areas of the body. It can provide high success rates not only for extremity reconstruction but also for scalp and pelvic reconstruction. The CSA matches well with the workhorse recipient vessels. The SAB is suitable when there is a vascular defect of the recipient artery. PMID- 26150221 TI - Laboratory animal research published in plastic surgery journals in 2014 has extensive waste: A systematic review. AB - Laboratory animal research must be designed in a manner that minimizes bias if it is to yield valid and reproducible results. In 2009, a survey that examined 271 animal studies found that 87% did not use randomization and 86% did not use blinding. This has been called "research waste" because it wasted time and resources. This systematic review measured the quantity of research waste in plastic surgery journals in 2014. METHOD: The PRISMA-P protocol was used. SCOPUS and PubMed searches were done for all animal studies published in 2014 in Aesthetic Plast Surg, Aesthet Surg J, Ann Plast Surg, JPRAS, J Plast Surg Hand Surg and Plast Reconstr Surg. These were supplemented by manual searches of the 2014 issues not indexed. Articles were analyzed for descriptions of randomization, randomization methodology, allocation concealment, and blinding of the primary outcome assessment. Corresponding authors who mentioned randomization without elaborating were emailed for details. RESULTS: 112 of 154 articles met the inclusion criteria. Only 24/112 (21.4%) had blinding of the primary outcome measure, 28/110 (25.5%) of articles that required randomization mentioned it. While 12/28 articles clearly described randomizing the intervention, only 4/28 described the method of randomization, and 2/28 mentioned allocation concealment. Only two authors responded and described the randomization methodology. CONCLUSION: The quality of plastic surgery laboratory animal research published in 2014 was poor. Use of the National Centre for the Replacement Refinement & Reduction of Animals in Research's "Animal Research: Reporting In Vivo Experiments" (ARRIVE) Guidelines by authors, and enforcement of them by editors and reviewers could improve research quality and reduce waste. PMID- 26150222 TI - Long-term results of a randomized controlled trial of T2 versus T2-T3 ablation in endoscopic thoracic sympathectomy for palmar hyperhidrosis. AB - BACKGROUND: Despite good short-term results and patient satisfaction with endoscopic thoracic sympathectomy (ETS), there has been much debate on the level of sympathectomy for treatment of palmar hyperhidrosis (PH) in terms of long-term clinical outcomes. OBJECTIVE: The aim of the study was to analyze the long-term recurrence and compensatory hyperhidrosis (CH) rates of ETS, comparing single level T2 against multi-level T2-T3 ablation in single patients. METHODS: Patients who had undergone treatment for PH with unilateral T2 and contralateral T2-T3 ablation in ETS were retrospectively reviewed. They were subjected to telephone interview using standardized set of interview script and questionnaire with a scoring system similar to hyperhidrosis disease severity scale. All patients were evaluated for comparison of symptom resolution, site and severity of CH, and satisfaction rates. To compare between T2 and T2-T3, the level of sympathectomy on one side is matched to the ipsilateral recurrence of PH and CH occurrence. RESULTS: Twenty-two patients with a mean age of 36.5 years could be reached. The mean follow-up was 8 years (range 38-153 months). The global recurrence rate for PH is 18%. CH was observed in 20 (91%) patients, and trunk compensation was the most common (18/22-82%), followed by lower limb (14/22-64%) and axilla (10/22 45%). Overall, 72.8% (16) of the patients were satisfied with the operation. Among the six patients who were not satisfied, two patients reported recurrence of symptoms, while four patients experienced some form of compensation. There was no absolute difference in the severity of sweating bilaterally for patients who reported recurrence of PH. The site and severity of CH were also bilaterally symmetrical for all patients. CONCLUSION: There was no difference in recurrence rates and CH between single-level (T2) and multi-level (T2-T3) ETSs in the long term. PMID- 26150224 TI - Laparoscopic parastomal hernia repair: No different than a laparoscopic ventral hernia repair? AB - BACKGROUND: Parastomal hernia (PH) is a common complication when a stoma is used. The high incidence (35-50%) and patient longevity have created a situation where patients are being referred for consideration of repair with more frequency. Due to the presence of an ostomy and the increased bacterial contamination of the area, the insertion of a prosthetic material is concerning for complications. Laparoscopic repair of parastomal hernias utilizing a modified Sugarbaker technique has been demonstrated to have excellent outcomes. The purpose of this study is to demonstrate that laparoscopic PH repair has outcomes similar to laparoscopic ventral hernia (LVH) repair without the presence of a stoma. METHODS: After obtaining institutional review board approval, patients with parastomal hernia who underwent laparoscopic repair using Sugarbaker technique between 2009 and 2012 were compared to patients with ventral hernias who underwent LVH repair in a retrospective review, with a match of 1:3. Data collected included demographics, comorbidities, operative time, defect size, and mesh size. Outcomes and complications were compared between the two groups. RESULTS: Twenty patients underwent Sugarbaker repair, and these cases were compared to 60 patients with ventral hernia that received LVH repair. There was no statistically significant difference in age, BMI, smoking status, ASA score, defect size, or mesh size between groups. Operative time was significantly longer in the PH group: 172 +/- 35 versus the LVH group: 94 +/- 32 min (p < 0.1). Length of stay was longer, 3 days (3-5.5) for PH versus 1 day (1-2.8) for LVH, p < 0.1. The two groups did not differ in terms of wound complications or recurrence, with a median follow-up of 37 days (IQ range 27-518). CONCLUSION: The Sugarbaker technique is as safe as LVH repair with no more complications given the presence of a stoma. PMID- 26150223 TI - A multicenter study of using carbon nanoparticles to show sentinel lymph nodes in early gastric cancer. AB - BACKGROUND: Lymph node metastasis occurs in approximately 10% of early gastric cancer. Preoperative or intra-operative identification of lymph node metastasis in early gastric cancer is crucial for surgical planning. The purpose of this study was to evaluate the feasibility of using carbon nanoparticles to show sentinel lymph nodes (SLNs) in early gastric cancer. METHODS: A multicenter study was performed between July 2012 and November 2014. Ninety-one patients with early gastric cancer identified by preoperative endoscopic ultrasonography were recruited. One milliliter carbon nanoparticles suspension, which is approved by Chinese Food and Drug Administration, was endoscopically injected into the submucosal layer at four points around the site of the primary tumor 6-12 h before surgery. Laparoscopic radical resection with D2 lymphadenectomy was performed. SLNs were defined as nodes that were black-dyed by carbon nanoparticles in greater omentum and lesser omentum near gastric cancer. Lymph node status and SLNs accuracy were confirmed by pathological analysis. RESULTS: All patients had black-dyed SLNs lying in greater omentum and/or lesser omentum. SLNs were easily found under laparoscopy. The mean number of SLNs was 4 (range 1 9). Carbon nanoparticles were around cancer in specimen. After pathological analysis, 10 patients (10.99%) had lymph node metastasis in 91 patients with early gastric cancer. SLNs were positive in 9 cases and negative in 82 cases. In pathology, carbon nanoparticles were seen in lymphatic vessels, lymphoid sinus, and macrophages in SLNs. When SLNs were positive, cancer cells were seen in lymph nodes. The sensitivity, specificity, and accuracy of black-dyed SLNs in early gastric cancers were 90, 100, and 98.9 %, respectively. No patient had any side effects of carbon nanoparticles in this study. CONCLUSIONS: It is feasible to use carbon nanoparticles to show SLNs in early gastric cancer. Carbon nanoparticles suspension is safe for submucosal injection. PMID- 26150225 TI - Novel method for hybrid endo-laparoscopic full-thickness gastric resection using laparoscopic transgastric suture passer device. AB - BACKGROUND: Current surgical methods for partial gastric full-thickness resections (FTRs) are limited by long operative times and risk of gastric content spillage, especially for lesions located at the posterior wall. We propose a simplified hybrid approach to FTR with reduced risk of spillage. METHODS: Resection margins were marked by endoscopic electrocautery to simulate a gastric lesion in the upper third of the posterior wall in eight pigs. A custom-made laparoscopic "suture passer" was made of a sharpened bendable dissecting forceps. Full-thickness sutures were alternatively passed from the serosa side with the suture passer through the gastric wall and grabbed endoluminally using an endoscopic grasper and vice versa. These transgastric sutures formed either a purse string (PS; n = 4) or a continuous horizontal mattress (HM; n = 4). Sutures were then fastened from the laparoscopic side, resulting in external outpouching of the lesion. The pouch was transected using 45-mm linear staplers. Operative time, resection margins, and number of staplers were evaluated. RESULTS: The combined approach allowed one to precisely place the sutures around the pseudo lesions, despite the inflated stomach, and it included all target markings. PS and HM methods were similar regarding time for transgastric suture (780 s +/- 219.1 s vs. 765 s +/- 179.2 s, p = .885), resection margins (1.3 +/- 1.0 cm vs. 0.8 +/- 0.6 cm, p = .248), and number of staplers (3.8 +/- 1.0 vs 3.3 +/- 0.5, p = .405). Stapling time (600 s +/- 189.7 s vs. 330 s +/- 24.5 s, p = .028) was significantly shorter in the HM technique. CONCLUSION: FTR with laparo-endoscopic transgastric suture application was feasible in the animal model. This technique allows one to achieve accurate resection margins with minimal risk of spillage. PMID- 26150227 TI - The effect of fasting on surgical performance. AB - BACKGROUND: It is unknown whether fasting has any impact on surgical performance. This simulator-based study investigates whether fasting affects surgical performance. METHODS: Twelve healthy medical students [seven women, mean age 26.5 years (range 23-34)] with no prior experience with surgical simulators underwent a short course introduction to the LapSim((r)) simulator. After having reached a predefined level, the participants performed five simulated salpingectomies on the LapSim((r)) simulator 5-30 days after the initial introduction. The procedures took place at 9 a.m. and 2 p.m. after fasting from 9 p.m. the previous day. Time used to complete the procedure, instrument movements and "blood loss" were registered. RESULTS: The participants performed significantly better at 2 p.m. compared with 9 a.m. with regard to time, "blood loss" and instrument movements except from instrument movements in the longitudinal axis with the left hand. CONCLUSION: The simulator-based study suggests that 17 h of fasting does not deteriorate surgical performance. Further studies on the effect of fasting on surgical performance are needed. PMID- 26150226 TI - Relationship between gastric pouch and weight loss after laparoscopic sleeve gastrectomy. AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is considered safe and effective even as conversion procedure after primary bariatric operations. The correlation between gastric pouch volumes and patients weight loss remains unclear. METHODS: To assess a correlation between the gastric remnant size and the weight loss, we reviewed 49 consecutive barium swallow UGS performed at our institute from August 2012 through May 2014 in LSG patients with symptoms and/or unsatisfactory weight loss. The anteroposterior (AP), laterolateral (LL) and vertical (CC) diameters of the gastric pouch were measured to calculate the volume by the formula of the ellipsoid (AP * LL * CC * 0.5). Patients were divided in two groups: group 1 without gastric pouch (n = 36) and group 2 with gastric pouch (n = 13). Correlation between pouch volume and weight loss data was calculated with t Student's and Fisher tests to compare the percent excess body mass index (BMI) and percent excess body mass loss (EBL) between two groups, and P < 0.05 was considered statistically significant. RESULTS: The mean percent EBL was 26.54 +/- 11.02 and 27.12 +/- 12.35 kg/m(2) in groups with and without pouch, respectively. The mean volume of the pouch after LSG was 17.13 +/- 21.56 mm(3). Pouch volume, when present, was not significantly correlated to weight loss (P = 0.88 95% CI, CL 19.88-33.20 group 2; CL 22.94-31.30 group 1). CONCLUSIONS: No statistical correlation was found between the volume of the gastric pouch and weight loss (percent EBL) after LSG in symptomatic or with unsatisfactory weight loss patients. PMID- 26150228 TI - Condiment-Derived 3D Architecture Porous Carbon for Electrochemical Supercapacitors. AB - The one-step synthesis of porous carbon nanoflakes possessing a 3D texture is achieved by cooking (carbonization) a mixture containing two condiments, sodium glutamate (SG) and sodium chloride, which are commonly used in kitchens. The prepared 3D porous carbons are composed of interconnected carbon nanoflakes and possess instinct heteroatom doping such as nitrogen and oxygen, which furnishes the electrochemical activity. The combination of micropores and mesopores with 3D configurations facilitates persistent and fast ion transport and shorten diffusion pathways for high-performance supercapacitor applications. Sodium glutamate carbonized at 800 degrees C exhibits high charge storage capacity with a specific capacitance of 320 F g(-1) in 6 m KOH at a current density of 1 A g( 1) and good stability over 10,000 cycles. PMID- 26150229 TI - Infraocclusion: Dental development and associated dental variations in singletons and twins. AB - OBJECTIVE: The aim of this study was to investigate the prevalence of selected dental variations in association with infraocclusion, as well as determining the effects of infraocclusion on dental development and tooth size, in singletons and twins. DESIGN: Two samples were analysed. The first sample comprised 1454 panoramic radiographs of singleton boys and girls aged 8-11 years. The second sample comprised dental models of 202 pairs of monozygotic and dizygotic twins aged 8-11 years. Adobe Photoshop CS5 was used to construct reference lines and measure the extent of infraocclusion (in mm) of primary molars on the panoramic radiographs and on 2D images obtained from the dental models. The panoramic radiographs were examined for the presence of selected dental variations and to assess dental development following the Demirjian and Willems systems. The twins' dental models were measured to assess mesiodistal crown widths. RESULTS: In the singleton sample there was a significant association of canines in an altered position during eruption and the lateral incisor complex (agenesis and/or small tooth size) with infraocclusion (P<0.001), but there was no significant association between infraocclusion and agenesis of premolars. Dental age assessment revealed that dental development was delayed in individuals with infraocclusion compared to controls. The primary mandibular canines were significantly smaller in size in the infraoccluded group (P<0.05). CONCLUSION: The presence of other dental variations in association with infraocclusion, as well as delayed dental development and reduced tooth size, suggests the presence of a pleiotropic effect. The underlying aetiological factors may be genetic and/or epigenetic. PMID- 26150230 TI - Vitamin E protects salivary glands dysfunction induced by ionizing radiation in rats. AB - The purpose of this study is to investigate the radioprotective effect of vitamin E as a natural product. Vitamin E protects the salivary glands dysfunction that is induced by ionizing radiation. It was analysed with radioisotope scintigraphy and then salivary gland to background counts ratio was calculated. Histopathological evaluation was performed. The rats were treated with vitamin E at dose of 400IU/kg 48, 24, and 1h before 15Gy gamma rays irradiation. The rats were evaluated for the salivary gland function through nuclear medicine protocol. Radiation causes significant salivary glands dysfunction at the 3rd and the 70th days with a reduction in radioactivity uptake in the salivary glands. Ratios of salivary gland to background radioactivities were 1.99+/-0.11, 1.58+/-0.08 and 1.92+/-0.04 for control, radiation, and vitamin E plus radiation groups, respectively. Vitamin E significantly improved salivary gland dysfunction induced by ionizing radiation in the rats. In conclusion, our results indicate protective effects of vitamin E against salivary gland dysfunction induced by gamma radiation. Thus, vitamin E is a promising radioprotective agent for patients who receive radiation in head and neck cancer therapy. PMID- 26150231 TI - Efficacy of walking aids on self-paced outdoor walking in individuals with COPD: A randomized cross-over trial. AB - BACKGROUND AND OBJECTIVE: Walking aids, such as rollator or draisine, improve mobility and functional exercise performance in individuals with chronic obstructive pulmonary disease (COPD) during an indoor 6-min walk test. However, this test does not reflect everyday walking, which is the most frequently reported problematic activity of daily life in individuals with COPD. To date, efficacy of walking aids during self-paced outdoor walking remains unknown. Therefore, we aimed to determine the efficacy of a rollator and draisine on self paced outdoor walking in individuals with COPD. METHODS: Fifteen individuals with COPD (68% men; age: 63 +/- 8 years; forced expiratory volume in 1 s: 40 +/- 14% predicted) performed three self-paced outdoor walking tests on two consecutive days: test 1 unaided, and tests 2 and 3 with rollator or draisine in random order. Participants had to walk as long as possible at their own pace. The test ended when participants needed to stop, with a maximum duration of 30 min. RESULTS: The use of rollator resulted in the highest walk distance and time (P < 0.05 vs unaided and draisine). Furthermore, individuals with COPD walked significantly further and longer during an unaided test compared with a draisine aided test (P < 0.05). Moreover, use of draisine resulted in a significantly higher walking speed, fewer strides, greater stride length, and higher step and stride variability (P < 0.05 vs unaided and rollator). CONCLUSION: To conclude, a rollator improves the self-paced outdoor walk distance and time in individuals with moderate and advanced COPD and a poor functional exercise capacity, whereas the use of a draisine had a detrimental effect compared with unaided walking. PMID- 26150232 TI - Pom1 gradient buffering through intermolecular auto-phosphorylation. AB - Concentration gradients provide spatial information for tissue patterning and cell organization, and their robustness under natural fluctuations is an evolutionary advantage. In rod-shaped Schizosaccharomyces pombe cells, the DYRK family kinase Pom1 gradients control cell division timing and placement. Upon dephosphorylation by a Tea4-phosphatase complex, Pom1 associates with the plasma membrane at cell poles, where it diffuses and detaches upon auto-phosphorylation. Here, we demonstrate that Pom1 auto-phosphorylates intermolecularly, both in vitro and in vivo, which confers robustness to the gradient. Quantitative imaging reveals this robustness through two system's properties: The Pom1 gradient amplitude is inversely correlated with its decay length and is buffered against fluctuations in Tea4 levels. A theoretical model of Pom1 gradient formation through intermolecular auto-phosphorylation predicts both properties qualitatively and quantitatively. This provides a telling example where gradient robustness through super-linear decay, a principle hypothesized a decade ago, is achieved through autocatalysis. Concentration-dependent autocatalysis may be a widely used simple feedback to buffer biological activities. PMID- 26150233 TI - Persistent left superior vena cava and cardiac transplantation: Anterior rerouting with anastomosis to the right atrium. PMID- 26150234 TI - Kidney cancer: BCOR mutations that might help in diagnosis of CCSK. PMID- 26150235 TI - Kidney cancer: Mice with Flcn knockout in proximal tubules-an in vivo model for multiple RCC subtypes. PMID- 26150237 TI - Paediatrics: Towards evidence-based management of paediatric RCC. PMID- 26150241 TI - Prostate cancer: miRNA-mRNA pairs are differently expressed in African American men. PMID- 26150242 TI - Who started first? Bird species visiting novel birdfeeders. AB - Adapting to exploit new food sources may be essential, particularly in winter, when the impact of food limitation on survival of individuals is critical. One of the most important additional sources of food for birds in human settlements is birdfeeders. At a large spatial scale, we experimentally provided birdfeeders with four different kinds of food to analyze exploitation and use of a novel food supply provided by humans. Nine species started foraging at the new birdfeeders. The species that exploited the new feeders the fastest was the great tit. Use of novel food sources was faster in urban habitats and the presence of other feeders reduced the time until a new feeder was located. Urbanization may be associated with behavioural skills, technical innovations and neophilia resulting in faster discovery of new food sources. This process is accelerated by the experience of feeder use in the vicinity, with a strong modifying effect of the number of domestic cats. PMID- 26150243 TI - Increased riboflavin production by manipulation of inosine 5'-monophosphate dehydrogenase in Ashbya gossypii. AB - Guanine nucleotides are the precursors of essential biomolecules including nucleic acids and vitamins such as riboflavin. The enzyme inosine-5' monophosphate dehydrogenase (IMPDH) catalyzes the ratelimiting step in the guanine nucleotide de novo biosynthetic pathway and plays a key role in controlling the cellular nucleotide pools. Thus, IMPDH is an important metabolic bottleneck in the guanine nucleotide synthesis, susceptible of manipulation by means of metabolic engineering approaches. Herein, we report the functional and structural characterization of the IMPDH enzyme from the industrial fungus Ashbya gossypii. Our data show that the overexpression of the IMPDH gene increases the metabolic flux through the guanine pathway and ultimately enhances 40 % riboflavin production with respect to the wild type. Also, IMPDH disruption results in a 100-fold increase of inosine excretion to the culture media. Our results contribute to the developing metabolic engineering toolbox aiming at improving the production of metabolites with biotechnological interest in A. gossypii. PMID- 26150244 TI - PEG-salt aqueous two-phase systems: an attractive and versatile liquid-liquid extraction technology for the downstream processing of proteins and enzymes. AB - Nowadays, there is an increasing demand to establish new feasible, efficient downstream processing (DSP) techniques in biotechnology and related fields. Although several conventional DSP technologies have been widely employed, they are usually expensive and time-consuming and often provide only low recovery yields. Hence, the DSP is one major bottleneck for the commercialization of biological products. In this context, polyethylene glycol (PEG)-salt aqueous two phase systems (ATPS) represent a promising, efficient liquid-liquid extraction technology for the DSP of various biomolecules, such as proteins and enzymes. Furthermore, ATPS can overcome the limitations of traditional DSP techniques and have gained importance for applications in several fields of biotechnology due to versatile advantages over conventional DSP methods, such as biocompatibility, technical simplicity, and easy scale-up potential. In the present review, various practical applications of PEG-salt ATPS are presented to highlight their feasibility to operate as an attractive and versatile liquid-liquid extraction technology for the DSP of proteins and enzymes, thus facilitating the approach of new researchers to this technique. Thereby, single- and multi-stage extraction, several process integration methods, as well as large-scale extraction and purification of proteins regarding technical aspects, scale-up, recycling of process chemicals, and economic aspects are discussed. PMID- 26150245 TI - Archaeal DNA polymerases in biotechnology. AB - DNA polymerase (pol) is a ubiquitous enzyme that synthesizes DNA strands in all living cells. In vitro, DNA pol is used for DNA manipulation, including cloning, PCR, site-directed mutagenesis, sequencing, and several other applications. Family B archaeal DNA pols have been widely used for molecular biological methods. Biochemical and structural studies reveal that each archaeal DNA pol has different characteristics with respect to fidelity, processivity and thermostability. Due to their high fidelity and strong thermostability, family B archaeal DNA pols have the extensive application on high-fidelity PCR, DNA sequencing, and site-directed mutagenesis while family Y archaeal DNA pols have the potential for error-prone PCR and random mutagenesis because of their low fidelity and strong thermostability. This information combined with mutational analysis has been used to construct novel DNA pols with altered properties that enhance their use as biotechnological reagents. In this review, we focus on the development and use of family B archaeal DNA pols. PMID- 26150246 TI - Prediction of T cell epitopes of Brucella abortus and evaluation of their protective role in mice. AB - Brucellae are Gram-negative intracellular bacteria that cause an important zoonotic disease called brucellosis. The animal vaccines are available but have disadvantage of causing abortions in a proportion of pregnant animals. The animal vaccines are also pathogenic to humans. Recent trend in vaccine design has shifted to epitope-based vaccines that are safe and specific. In this study, efforts were made to identify MHC-I- and MHC-II-restricted T cell epitopes of Brucella abortus and evaluate their vaccine potential in mice. The peptides were designed using online available immunoinformatics tools, and five MHC-I- and one MHC-II-restricted T cell peptides were selected on the basis of their ability to produce interferon gamma (IFN-gamma) in in vivo studies. The selected peptides were co-administered with poly DL-lactide-co-glycolide (PLG) microparticles and evaluated for immunogenicity and protection in BALB/c mice. Mice immunized with peptides either entrapped in PLG microparticles (EPLG-Pep) or adsorbed on PLG particles (APLG-Pep) showed significantly higher splenocyte proliferation and IFN gamma generation to all selected peptides than the mice immunized with corresponding irrelevant peptides formulated PLG microparticles or phosphate buffered saline (PBS). A significant protection compared to PBS control was also observed in EPLG-Pep and APLG-Pep groups. A plasmid DNA vaccine construct (pVaxPep) for peptides encoding DNA sequences was generated and injected to mice by in vivo electroporation. Significant protection was observed (1.66 protection units) when compared with PBS and empty vector control group animals. Overall, the MHC-I and MHC-II peptides identified in this study are immunogenic and protective in mouse model and support the feasibility of peptide-based vaccine for brucellosis. PMID- 26150247 TI - Isomerases for biotransformation of D-hexoses. AB - Monosaccharides are polyhydroxyl compounds containing several chiral carbons, giving rise to tens of isomeric forms. Only minority of them are natural carbohydrates existing in nature abundantly, and most of them are rarely in nature, called rare sugars. These rare sugars attract increasing attention because of their low-calorie property and promising beneficial effects. Izumoring strategy has been established for linking all monosaccharides by three types of enzymes including ketose 3-epimerases, polyol dehydrogenases, and aldose isomerases. Recently, more attention has been paid on the Izumoring of hexoses, especially the D-zone hexoses. So far, at least ten isomerases have been used for the isomerization reactions between D-aldohexoses and D-ketohexoses. In this article, the interconnections and potential physiological effects of D ketohexoses and D-aldohexoses are summarized, the D-zone hexose Izumoring is shown by giving the exact biocatalysts, and importantly, the isomerases for D hexose biotransformation are reviewed in detail. PMID- 26150248 TI - Announcing our finalists. AB - Each year, Bioanalysis and Bioanalysis Zone run the Young Investigator Award to identify and reward promising early-career researchers in our community. This year, 12 young scientists were nominated for the award and their profiles have been featured on our sister website, Bioanalysis Zone. Our Advisory Panel helped us narrow down the nominees to the five most exceptional candidates. PMID- 26150249 TI - Primary fallopian tube carcinoma: review of MR imaging findings. AB - OBJECTIVES: To review the epidemiological and clinical features of primary fallopian tube carcinoma (PFTC), and to illustrate the spectrum of MRI findings, with pathological confirmation. METHODS: This article reviews the relevant literature on the epidemiological, clinical, and imaging features of primary fallopian tube carcinoma, with pathological confirmation, using illustrations from the authors' teaching files. RESULTS: Primary fallopian tube carcinoma came under focus over the last few years due to its possible role on the pathogenesis of high-grade serous epithelial ovarian and peritoneal cancers. Typical symptoms, together with the presence of some of the most characteristic MRI signs, such as a "sausage-shaped" pelvic mass, hydrosalpinx, and hydrometra, may signal the presence of primary fallopian cancer, and allow the radiologist to report it as a differential diagnosis. CONCLUSIONS: Primary fallopian tube carcinoma has a constellation of clinical symptoms and magnetic resonance imaging features, which may be diagnostic. Although these findings are not present together in the majority of cases, radiologists who are aware of them may include the diagnosis of primary fallopian tube cancer in their report more frequently and with more confidence. TEACHING POINTS: * PFTC may be more frequent than previously thought * PFTC has specific clinical and MRI characteristics * Knowledge of typical PFTC signs enables its inclusion in the differential diagnosis * PFTC is currently staged under the 2013 FIGO system * PFTC is staged collectively with ovarian and peritoneal neoplasms. PMID- 26150250 TI - Effect of the stop-flow technique on cardiac retention of c-kit positive human cardiac stem cells after intracoronary infusion in a porcine model of chronic ischemic cardiomyopathy. AB - It is commonly thought that the optimal method for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/vascular wall contact, enhance adhesion, and promote extravasation of cells into the interstitial space. However, occlusion of a coronary artery with a balloon involves serious risks of vascular damage and/or dissection, particularly in non-stented segments such as those commonly found in patients with heart failure. It remains unknown whether the use of the stop-flow technique results in improved donor cell retention. Acute myocardial infarction was produced in 14 pigs. One to two months later, pigs received 10 million indium-111 oxyquinoline (oxine)-labeled c-kit(pos) human cardiac stem cells (hCSCs) via intracoronary infusion with (n = 7) or without (n = 7) balloon inflation. Pigs received cyclosporine to prevent acute graft rejection. Animals were euthanized 24 h later and hearts harvested for radioactivity measurements. With the stop-flow technique, the retention of hCSCs at 24 h was 5.41 +/- 0.80 % of the injected dose (n = 7), compared with 4.87 +/- 0.62 % without coronary occlusion (n = 7), (P = 0.60). When cells are delivered intracoronarily in a clinically relevant porcine model of chronic ischemic cardiomyopathy, the use of the stop-flow technique does not result in greater myocardial cell retention at 24 h compared with non-occlusive infusion. These results have practical implications for the design of cell therapy trials. Our observations suggest that the increased risk of complications secondary to coronary manipulation and occlusion is not warranted. PMID- 26150251 TI - Quantification of volatile-alkylated selenium and sulfur in complex aqueous media using solid-phase microextraction. AB - Biologically produced volatile-alkylated Se and S compounds play an important role in the global biogeochemical Se and S cycles, are important constituents of odorous industrial emissions, and contribute to (off-)flavors in food and beverages. This study presents a fully automated direct-immersion solid-phase microextraction (DI-SPME) method coupled with capillary gas chromatography-mass spectrometry (GC/MS) for the simultaneous quantification of 10 volatile-alkylated Se and S compounds in complex aqueous media. Instrumental parameters of the SPME procedure were optimized to yield extraction efficiencies of up to 96% from complex aqueous matrices. The effects of sample matrix composition and analyte transformation during sample storage were critically assessed. With the use of internal standards and procedural calibrations, the DI-SPME-GC/MS method allows for trace-level quantification of volatile Se and S compounds in the ng/L range (e.g. down to 30 ng/L dimethyl sulfide and 75 ng/L dimethyl selenide). The applicability and robustness of the presented method demonstrate that the method may be used to quantify volatile Se and S compounds in complex aqueous samples, such as industrial effluents or food and beverage samples. PMID- 26150252 TI - Application of polymeric macroporous supports for temperature-responsive chromatography of pharmaceuticals. AB - A macroporous particulate support prepared previously by reactive gelation under shear and functionalized with poly(N-isopropylacrylamide), PNIPAM, brushes of variable length is applied for temperature-responsive chromatography, whereby temperature modulates hydrophobic interactions. Several different analytes, including small pharmaceuticals, peptides, proteins and monoclonal antibodies are employed. Contrary to the most commonly observed behavior in conventional chromatography, increasing retention is observed at elevated temperatures. Peak broadening is quantified using the peak standard deviation, which depends on both the polymer chain conformation and analyte adsorptivity. The favorable effect of grafted polymer thickness on retention becomes progressively less pronounced for thicker grafted PNIPAM layers. The effect of eluent composition on solute-sorbent interactions was investigated by introducing NaCl, methanol, dioxane and by varying the pH. Salt or organic solvent addition affects apart from the analytes solution properties, the hydrophobicity of the stationary phase itself. Frontal analyses performed at different temperatures to determine dynamic binding capacities, indicate small mass transfer resistances imposed by this novel packing material. PMID- 26150253 TI - Model-based description of peptide retention on doped reversed-phase media. AB - Reversed-phase (RP) chromatography is one of the main tools for the preparative purification of therapeutic peptides. In previous works [1,2], a new type of RP chromatography, doped reversed-phase chromatography (DRP) was presented. By adding small amounts (up to 15% of the surface ligands) of repulsive ion exchange ligands to a traditional RP material, significant improvements in peptide purification performance were observed, at the same or in similar operating conditions. These improvements included increases in selectivity in diluted conditions (up to twice as high), increases in yield in preparative conditions (up to 20% higher) and in productivity in preparative conditions (up to twice as high), when compared to RP materials [2]. A proper physical model is developed in this work to quantitatively explain and rationalize this behavior. The developed model is then used to correctly fit the retention data of several peptides in different buffering conditions. The increase in selectivity is related to a controlled decrease in free surface area available for adsorption due to the ionic ligands creating a repulsive sphere the analytes cannot enter. This decrease in adsorption surface is calculated using Debye-Huckel theory, and in combination with linear solvent strength theory, allows for the quantitative description of peptide retention on DRP media. PMID- 26150254 TI - Nanocatalysis in Flow. AB - Nanocatalysis in flow is catalysis by metallic nanoparticles (NPs; 1-50 nm) performed in microstructured reactors. These catalytic processes make use of the enhanced catalytic activity and selectivity of NPs and fulfill the requirements of green chemistry. Anchoring catalytically active metal NPs within a microfluidic reactor enhances the reagent/catalyst interaction, while avoiding diffusion limitations experienced in classical approaches. Different strategies for supporting NPs are reviewed herein, namely, packed-bed reactors, monolithic flow-through reactors, wall catalysts, and a selection of novel approaches (NPs embedded on nanotubes, nanowires, catalytic membranes, and magnetic NPs). Through a number of catalytic reactions, such as hydrogenations, oxidations, and cross coupling reactions, the advantages and possible drawbacks of each approach are illustrated. PMID- 26150255 TI - Individualized care for portal hypertension: Not quite yet. PMID- 26150256 TI - Optimal management of hepatitis B virus infection - EASL Special Conference. AB - There have been great strides in the management of chronic hepatitis B virus (HBV) infection, but considerable challenges remain. The European Association for the Study of the Liver (EASL) convened a special conference focusing on all clinical aspects of the management of this disease. Immigration patterns are having a huge effect on the incidence, prevalence and genotype predominance of HBV in many European countries. In recent years there has been significant progress in our understanding of the virology and immunopathology of HBV, particularly the identification of the entry receptor for HBV conferring its hepatotropism, sodium taurocholate co-transporting polypeptide, and a better understanding of the regulation of the covalently closed circular DNA form of HBV - the major barrier to cure. However, more fundamental scientific research is needed. Serum biomarkers and transient elastography offer equivalent performance in the grading of disease stage and progression and monitoring of treatment. Occult HBV infection is often overlooked, but has many important implications for e.g., immuno-suppression, liver transplantation and the progression and severity of liver diseases from other causes. Hepatitis B e antigen positive immunotolerant patients, who are a significant source of horizontal and vertical transmission, are at risk for developing active chronic hepatitis B, but current treatment options are ineffective. Pegylated interferon therapy, given for a finite duration, offers sustained off-treatment responses in a minority of patients. Nucleos(t)ide analogues suppress the virus, improve liver histological lesions, reverse cirrhosis in the majority of cases, and improve survival, but 'cure' cannot be achieved. There is also a pressing need for novel HBV/hepatitis D virus co-infection therapies. Novel therapeutic strategies, e.g. immunomodulation, RNA interference and viral entry inhibition have demonstrated promising early results. PMID- 26150257 TI - The concept and evolution of involved site radiation therapy for lymphoma. AB - We describe the development of radiation therapy for lymphoma from extended field radiotherapy of the past to modern conformal treatment with involved site radiation therapy based on advanced imaging, three-dimensional treatment planning and advanced treatment delivery techniques. Today, radiation therapy is part of the multimodality treatment of lymphoma, and the irradiated tissue volume is much smaller than before, leading to highly significant reductions in the risks of long-term complications. PMID- 26150258 TI - Gender differences in colorectal cancer survival in Japan. AB - BACKGROUND: A gender difference in survival has been documented in colorectal cancer (CRC) patients, although the underlying mechanism remains undefined. This study aimed to gain improved insight into this difference, with a special focus on improved cancer-specific survival. METHODS: The study population consisted of 82,402 patients with invasive CRC who had undergone surgery in Japan between 1985 and 2004. To estimate improved survival, multivariate adjustment using patient demographics and tumor characteristics was performed. RESULTS: Patient characteristics changed over time. The 5-year survival rates increased from 66.5 to 76.3 % during the study period. Higher survival rates persisted in women over time (multivariate-adjustment model-hazard ratio [HR] 0.87, 95 % confidence interval [CI] 0.85-0.90). Patients who received surgery during the period 2000 2004 had significantly longer survival than those during the period 1985-1989 (men: HR 0.70, 95 % CI 0.67-0.74; women: HR 0.72, 95 % CI 0.67-0.76). However, there was no gender difference regarding improved survival. CONCLUSIONS: A reduced risk of cancer-specific death for women relative to men persisted over time; however, enhancement of survival was equally observed in both genders. Identification of factors associated with gender differences and changes over time in CRC survival may serve as targets for further improvement. PMID- 26150259 TI - Comparison of clinical and functional outcome between surgical treatment and carbon ion radiotherapy for pelvic chondrosarcoma. AB - BACKGROUND: As there are no reports of studies in patients with pelvic chondrosarcoma treated with carbon ion radiotherapy (CIRT), the aim of this study was to evaluate the applicability of CIRT for patients with chondrosarcoma of the pelvis. METHODS: The medical records of 31 patients with chondrosarcoma of the pelvis treated either by surgical resection or by CIRT between 1983 and 2014 were reviewed. There were 22 males and 9 females with a median age of 43 years (range 16-77 years). The median duration of follow-up was 66 months (range 5-289 months). Twenty-four patients underwent surgery, and 7 patients received CIRT (70.4 GyE in 16 fractions over 4 weeks). RESULTS: The overall local recurrence rate was 32 %, and the estimated overall 5- and 10-year survival rates were 72 and 57 %, respectively. The mean Musculoskeletal Tumor Society functional score was 59 %. The treatment procedures (surgery or CIRT) did not affect overall survival (P = 0.347). However, the patients who underwent surgery had impaired function compared with those who received CIRT (P = 0.03). CONCLUSION: Although more patients need to be monitored to assess the clinical and functional outcomes of CIRT for patients with chondrosarcoma of the pelvis, this treatment might offer an acceptable alternative. PMID- 26150260 TI - Effect of hyperinsulinaemia-hyperaminoacidaemia on leg muscle protein synthesis and breakdown: reassessment of the two-pool arterio-venous balance model. AB - Accurate measurement of muscle protein turnover is critical for understanding the physiological processes underlying muscle atrophy and hypertrophy. Several mathematical approaches, used in conjunction with a tracer amino acid infusion, have been described to derive protein synthesis and breakdown rates from a two pool (artery-vein) model. Despite apparently common underlying principles, these approaches differ significantly (some seem to not take into account arterio venous shunting of amino acids, which comprises ~80-90% of amino acids appearing in the vein) and most do not specify how tracer enrichment (i.e. mole percent excess (MPE) or tracer-to-tracee ratio (TTR)) and amino acid concentration (i.e. unlabelled only or total labelled plus unlabelled) should be expressed, which could have a significant impact on the outcome when using stable isotope labelled tracers. We developed equations that avoid these uncertainties and used them to calculate leg phenylalanine (Phe) kinetics in subjects who received a [(2) H5 ]Phe tracer infusion during postabsorptive conditions and during a hyperinsulinaemic-euglycaemic clamp with concomitant protein ingestion. These results were compared with those obtained by analysing the same data with previously reported equations. Only some of them computed the results correctly when used with MPE as the enrichment measure and total (tracer+tracee) Phe concentrations; errors up to several-fold in magnitude were noted when the same approaches were used in conjunction with TTR and/or unlabelled concentration only, or when using the other approaches (irrespective of how concentration and enrichment are expressed). Our newly developed equations should facilitate accurate calculation of protein synthesis and breakdown rates. PMID- 26150262 TI - Corrigendum. PMID- 26150261 TI - Antidiarrhoeic effect of Eugenia dysenterica DC (Myrtaceae) leaf essential oil. AB - Essential oil from Eugenia dysenterica leaves was able to inhibit both the diarrhoea and enteropooling induced by castor oil; however, the distance travelled by charcoal meal in the intestine was not change. These data suggest that the antidiarrhoeic effect of the essential oil from E. dysenterica leaves is related to its ability to inhibit intestinal secretion and/or to increase intestinal absorption. PMID- 26150263 TI - Environmental determinants of the spatial distribution of Mesocestoides spp. and sensitivity of flotation method for the diagnosis of mesocestoidosis. AB - Mesocestoides spp. are zoonotic cestodes of wild and domesticated carnivores. Although the adult stages are relatively harmless intestinal parasites, the metacestode stages (tetrathyridia) can be responsible for life-threatening peritonitis and pleuritis in several species including dogs, cats, non-human primates and probably man. The aim of the present study was to reveal the spatial distribution pattern of Mesocestoides spp. in the most important final hosts, red foxes (Vulpes vulpes), to analyse the relationship of these patterns with landscape and climate by geographical information systems and to evaluate faecal flotation method for the detection of infection in the final host. Fox carcasses, representing 0.5% of the total fox population were randomly selected out of all the foxes of Hungary. The intestinal tract was examined by sedimentation and counting technique. The sensitivity of the flotation method was evaluated by the testing of the faecal samples of 180 foxes infected with Mesocestoides spp. The prevalence of infection was high in foxes (45.8%; 95% CI=41.0-50.6%), and the parasite was detected in all areas of Hungary. The high prevalence of the parasite in foxes suggests that the infection might also be common in outdoor dogs and cats. Mesocestoides infection could not be detected in any of the foxes by flotation method indicating that the sensitivity of the method is less than 0.6%. Therefore, almost all canine and feline infections remain undetected in the veterinary practice. Based on the statistical analysis, the altitude was the only determinant of the spatial distribution of Mesocestoides spp. indicating that infections in carnivores including dogs and cats can be expected mainly in midland regions (150-750 m above sea level). It might be attributed to the altitude-dependent species richness and abundance of the intermediate and final hosts of the parasite. PMID- 26150264 TI - What Safe Zone? The Vast Majority of Dislocated THAs Are Within the Lewinnek Safe Zone for Acetabular Component Position. AB - BACKGROUND: Numerous factors influence total hip arthroplasty (THA) stability including surgical approach and soft tissue tension, patient compliance, and component position. One long-held tenet regarding component position is that cup inclination and anteversion of 40 degrees +/- 10 degrees and 15 degrees +/- 10 degrees , respectively, represent a "safe zone" as defined by Lewinnek that minimizes dislocation after primary THA; however, it is clear that components positioned in this zone can and do dislocate. QUESTIONS/PURPOSES: We sought to determine if these classic radiographic targets for cup inclination and anteversion accurately predicted a safe zone limiting dislocation in a contemporary THA practice. METHODS: From a cohort of 9784 primary THAs performed between 2003 and 2012 at one institution, we retrospectively identified 206 THAs (2%) that subsequently dislocated. Radiographic parameters including inclination, anteversion, center of rotation, and limb length discrepancy were analyzed. Mean followup was 27 months (range, 0-133 months). RESULTS: The majority (58% [120 of 206]) of dislocated THAs had a socket within the Lewinnek safe zone. Mean cup inclination was 44 degrees +/- 8 degrees with 84% within the safe zone for inclination. Mean anteversion was 15 degrees +/- 9 degrees with 69% within the safe zone for anteversion. Sixty-five percent of dislocated THAs that were performed through a posterior approach had an acetabular component within the combined acetabular safe zones, whereas this was true for only 33% performed through an anterolateral approach. An acetabular component performed through a posterior approach was three times as likely to be within the combined acetabular safe zones (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.6) than after an anterolateral approach (OR, 0.4; 95% CI, 0.2-0.7; p < 0.0001). In contrast, acetabular components performed through a posterior approach (OR, 1.6; 95% CI, 1.2-1.9) had an increased risk of dislocation compared with those performed through an anterolateral approach (OR, 0.8; 95% CI, 0.7-0.9; p < 0.0001). CONCLUSIONS: The historical target values for cup inclination and anteversion may be useful but should not be considered a safe zone given that the majority of these contemporary THAs that dislocated were within those target values. Stability is likely multifactorial; the ideal cup position for some patients may lie outside the Lewinnek safe zone and more advanced analysis is required to identify the right target in that subgroup. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26150265 TI - Editorial: Is It Time to End Surgeon-Industry Consulting? PMID- 26150266 TI - Medicolegal Sidebar: Informed Consent in the Information Age. PMID- 26150267 TI - Typing TREX1 gene in patients with systemic lupus erythematosus. AB - An impaired expression of interferon-alpha regulated genes has been reported in patients with either systemic lupus erythematosus (SLE) or Aicardi-Goutieres syndrome (AGS), a rare monogenic encephalopathy with onset in infancy. One of mutations causing AGS is located in the TREX1 gene on chromosome 3. Heterozygous mutations in TREX1 were reported in SLE patients. TREX1 is a DNA exonuclease with specificity for ssDNA. An impairment of its activity may result in the accumulation of nucleid acid. A recent study described a significant association between a haplotype including several common single nucleotide polymorphisms (SNPs) of TREX1 and neurological manifestations in European SLE patients. Fifty one SLE patients were screened for TREX1 gene, and the corresponding data were collected from clinical charts. A novel heterozygous variant (p.Asp130Asn) was identified in one patient and in none of 150 controls. A missense variation was located in one of the three active sites of the gene and was classified as probably damaging. Variations of SNP rs11797 were detected in 33 SLE patients and a variation of rs3135944 in one. A significantly higher rate of the minor allele (T nucleotide) of SNP rs11797 was found in SLE patients with neuropsychiatric manifestations [12/16 (75%) vs 28/86 (32.5%) O=0.002, odds ratio=6.42 95% confidence interval (1.7-26.2)]. Only 1 out of 8 patients (12.5%) with neuropsychiatric SLE carried the wild-type form in homozygosity. Although we analyzed a small number of patients, we found a novel variation of TREX1, which may be pathogenic. The polymorphism of rs11797 was more frequent in SLE patients with neurological manifestations. PMID- 26150268 TI - Evolution in the use of musculoskeletal ultrasonography in a Rheumatology Unit over 14 years. AB - The aim of this article is to evaluate the use of musculoskeletal ultrasound in the daily clinical practice of a rheumatology unit. We conducted a descriptive retrospective analysis of the ultrasound examinations performed during 2011 and a comparison of these examinations with those performed between 1998 and 2003 and between 2007 and 2008. A total of 712 ultrasound examinations performed in 2011 were reviewed. Out of the total, examinations of individual areas of the body represented 11.6% versus 45.9% of the examinations made between 2007 and 2008 and 100% of those performed before 2003. The remaining 88.4% of ultrasound examinations performed in 2011 were intended to investigate inflammation in 25.8%, differential diagnosis of arthralgia in 17.1%, enthesis in 12.6% and temporal arteries in 17.3%, and to conduct ultrasound-guided procedures in 10.6% and study microcrystalline pathologies in 4.7%. In our unit, ultrasonography is evolving from being a mere investigation of individual areas of the body to becoming a clinical information tool, which contributes to the diagnosis and monitoring of the disease activity in the patient as a whole. PMID- 26150269 TI - Cytomegalovirus ileocolitis in a rheumatoid arthritis patient: case report and literature review. AB - Rheumatoid arthritis (RA) is an autoimmune, systemic, chronic, inflammatory disease generally treated with various immunosuppressive drugs. Cytomegalovirus (CMV) is an opportunistic, viral infection that is commonly seen in immunosuppressed patients. A sixty-four-year old female diagnosed with RA and treated with immunosuppressive agents was admitted to our rheumatology outpatient service with complaints of diarrhea and abdominal pain, which had lasted longer than four weeks. The patient's colonoscopy revealed inflamed and ulcerated areas in the colon and in the terminal ileum. A biopsy showed intra-nuclear inclusion particles consistent with CMV. We started an oral valganciclovir therapy in this serum-CMV-polymerase chain reaction-positive patient. The concomitant use of immunosuppressive agents and anti-viral drugs eased the patient's complaints, and the endoscopic picture improved. Consequently, cytomegalovirus ileocolitis in immunosuppressed patients admitted with severe diarrhea must be considered in the differential diagnosis. PMID- 26150270 TI - Coexistence of axial spondyloarthritis and thromboangiitis obliterans in a young woman. AB - A peculiar coexistence of axial spondyloarthritis and ischemia of the feet and the fourth finger of the left hand in a young woman, who was a heavy smoker, is discussed in this report. This picture was considered within the context of thromboangiitis obliterans. Positivity of anti-nuclear antibodies and mild elevation of inflammatory parameters were noted. Computed tomography angiograms of upper and lower limbs showed luminal narrowing and occlusion of the left humeral, left anterior/posterior tibial and right anterior tibial arteries. Daily iloprost perfusions were started, and smoking cessation was strongly recommended. Coldness and rest pain in the distal extremities improved within a few weeks. The possibility that spondyloarthritis might precede the clinical picture of thromboangiitis obliterans should be considered in heavy smokers. PMID- 26150271 TI - Systemic sclerosis sine scleroderma: a case report of anterior uveitis. AB - Systemic sclerosis (SSc) sine scleroderma (ssSSc) is characterized by the absence of skin involvement, despite other manifestations of systemic sclerosis are present. It is not known whether sSSc represents a forme fruste of limited cutaneous SSc or a distinct entity, but the 2013 American College of Rheumatology/European League Against Rheumatism criteria for the classification of SSc have considered SSc without skin involvement to be a distinct subset. The authors present the case of a 70-year old female that was referred for a consultation for Raynaud's phenomenon and a chronic anterior uveitis (CAU). She had a history of dysphagia, diffuse pulmonary emphysema and a biopsy-documented fibrosis of the upper lobes, and an idiopathic non-ischemic dilated cardiomyopathy with severe left ventricle systolic dysfunction and left bundle branch block. Anti-nuclear and anti-centromere antibodies were positive, while manometry revealed distal esophageal hypomotility. After establishing the diagnosis of ssSSc and starting immunosuppression, the ocular disease improved, while the lung and heart diseases remained stable. This case underlines that it is very important to suspect SSc when CAU is present and/or skin thickening is absent. To our knowledge, this is the first report of CAU in a patient with ssSSc. PMID- 26150272 TI - Octogenarian with an untreated femoral neck fracture: upright position during the postoperative course after aortic valve replacement. AB - We describe a patient with a femoral neck fracture undergoing an aortic valve replacement. The study design was a case report. An 82-year-old female with an untreated right femoral neck fracture, and a severe aortic valve stenosis was admitted to a cardiac surgery department for surgical treatment of the valve disease. She underwent aortic valve replacement with a sutureless biological valve prosthesis through a partial sternotomy. At an early stage, the patient was instructed to make postural changes in the standing position. As a result, she was able to perform body movements associated with either a sitting or standing position. This case shows that appropriate early mobilization of a patient with a femoral neck fracture is feasible after aortic valve replacement, even though this does not necessarily mean that the patient needs to walk. PMID- 26150273 TI - A method for counting monosodium urate crystals in synovial fluid. AB - This study was aimed to standardize the technique for counting monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with gout. A total of 52 SF specimens were examined under a polarized light microscope. The amount of SF ranged between 0.1 and 45 mL (median 3 mL). MSU crystals were counted in four areas with the same size at 400x magnification. Cytological examination of the same specimens was also performed. Median leukocyte count was 400 cells/mm3 (range 50-14,000 cells/mm3), with a median percentage of polymorphonuclear leukocytes of 9% (range 0%-98%). Median crystal count was 179.5 (range 3-1600). Inter- reader and intra-reader agreement in crystal counting were good with a weighed k of 0.89 [95% confidence interval (CI) 0.85-0.94] and 0.89 (95% CI 0.84 0.93), respectively. Our data indicate that the SF MSU crystal count is a feasible and highly reliable technique. PMID- 26150274 TI - Sjogren's syndrome and mean platelet volume. PMID- 26150275 TI - Artificial biomembrane based on DPPC--Investigation into phase transition and thermal behavior through ellipsometric techniques. AB - Organic thin film deposition presents a multiplicity of challenges. Most notably, layer thickness control, homogeneity and subsequent characterization have been not cleared yet. Phospholipid bilayers are frequently used to model cell membranes. Bilayers can be disrupted by changes in mechanical stress, pH and temperature. The strategy presented in this article is based on thermal study of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) through analysis of slight changes in material thickness. The sample was prepared by depositing X- or Y-type DPPC bilayers using Langmuir-Blodgett technique over silicon wafer. Thus, molecular inclination degree, mobility and stability of phases and their respective phase transitions were observed and analyzed through ellipsometric techniques during heating cycles and corroborated by Grazing Incidence X-ray Diffraction and Atomic Force Microcopy measurements. DPPC functional group vibrations were detected by Raman spectra analysis. Scanning Electron Microscope with Field Emission gun (FE-SEM) and conventional SEM micrographs were also used to characterize sample morphology, demonstrating that homogenous bilayer formations coexist with some vesicles or micelles at surface level. Contact angle measurements corroborate DPPC surface wettability, which is mainly related to surface treatment methods of silicon wafer used to create either hydrophilic or hydrophobic nature regarding the substrate surface. Also, shifting and intensity changes of certain functional groups into Raman spectra confirm water presence between DPPC layers. Signal analysis detects certain interdigitation between aliphatic chains. These studies correspond to the base of future biosensors based on proteins or antimicrobial peptides stabilized into phospholipid bilayers over thin hydrogel films as moist scaffold. PMID- 26150276 TI - [Peritoneal tumor pathology: case n(o) 2: a "sticky" peritoneal tumor]. PMID- 26150278 TI - Broadband Light-Harvesting Molecular Triads with High FRET Efficiency Based on the Coumarin-Rhodamine-BODIPY Platform. AB - Broadband capturing and FRET-based light-harvesting molecular triads, CRBs, based on the coumarin-rhodamine-BODIPY platform were rationally designed and synthesized. The absorption band of CRBs starts from blue-green to yellow-orange regions (330-610 nm), covering the strong radiation scope of sunlight. The peripheral coumarin and BODIPY chromophore energy could transfer to the central acceptor rhodamine by a one-step direct way. The energy of the coumarin moiety could also transfer to the BODIPY unit, subsequently transferring to the rhodamine core by two-step sequential ways. Both the efficiencies of the coumarin moiety and the BODIPY unit to the rhodamine core in CRBs, determined by two different ways, are very high. PMID- 26150277 TI - Decadal warming causes a consistent and persistent shift from heterotrophic to autotrophic respiration in contrasting permafrost ecosystems. AB - Soil carbon in permafrost ecosystems has the potential to become a major positive feedback to climate change if permafrost thaw increases heterotrophic decomposition. However, warming can also stimulate autotrophic production leading to increased ecosystem carbon storage-a negative climate change feedback. Few studies partitioning ecosystem respiration examine decadal warming effects or compare responses among ecosystems. Here, we first examined how 11 years of warming during different seasons affected autotrophic and heterotrophic respiration in a bryophyte-dominated peatland in Abisko, Sweden. We used natural abundance radiocarbon to partition ecosystem respiration into autotrophic respiration, associated with production, and heterotrophic decomposition. Summertime warming decreased the age of carbon respired by the ecosystem due to increased proportional contributions from autotrophic and young soil respiration and decreased proportional contributions from old soil. Summertime warming's large effect was due to not only warmer air temperatures during the growing season, but also to warmer deep soils year-round. Second, we compared ecosystem respiration responses between two contrasting ecosystems, the Abisko peatland and a tussock-dominated tundra in Healy, Alaska. Each ecosystem had two different timescales of warming (<5 years and over a decade). Despite the Abisko peatland having greater ecosystem respiration and larger contributions from heterotrophic respiration than the Healy tundra, both systems responded consistently to short- and long-term warming with increased respiration, increased autotrophic contributions to ecosystem respiration, and increased ratios of autotrophic to heterotrophic respiration. We did not detect an increase in old soil carbon losses with warming at either site. If increased autotrophic respiration is balanced by increased primary production, as is the case in the Healy tundra, warming will not cause these ecosystems to become growing season carbon sources. Warming instead causes a persistent shift from heterotrophic to more autotrophic control of the growing season carbon cycle in these carbon-rich permafrost ecosystems. PMID- 26150279 TI - Enhanced photocatalytic activities of the heterostructured upconversion photocatalysts with cotton mediated on TiO2/ZnWO4:Yb3+,Tm3. AB - To improve the photocatalytic efficiency and make full use of solar energy, ZnWO(4):Yb(3+),Tm(3+) (ZYT) was introduced as the upconversion luminescence agent on TiO(2) with a cotton template, and novel upconversion photocatalysts of TiO(2)/ZnWO(4):Yb(3+),Tm(3+) (TZYT-C) were synthesized and optimized with 5%-30% of ZYT. The heterostructure between ZYT and TiO(2) was formed in the TZYT-C composites with the presence of tube-like morphologies due to the addition of the cotton template. UV (364 nm) and blue (484 nm) light was emitted from ZYT upon 980 nm NIR irradiation. The BET specific surface areas of all the TZYT-C composites increased from 37 m(2) g(-1) (TiO(2)-C) to the maximum value of 75 m(2) g(-1) on 5%TZYT-C. The photocatalytic activities of the TZYT-C composites were tested using the degradation process of methyl orange (MO). 5%TZYT-C showed the highest degradation efficiency, with a value of 55.6% under sun-like irradiation for 210 min. The same performance was observed on 5%TZYT-C under NIR (lambda >= 780 nm) irradiation, with a maximum removal rate of 9.02%, since 5%TZYT-C showed the most efficient electron-hole (e(-)/h(+)) pair separation, compared to ZYT and other TZYT-C composites. PMID- 26150280 TI - High efficient multifunctional Ag3PO4 loaded hydroxyapatite nanowires for water treatment. AB - Organic, inorganic, and biological pollutants are typical water contaminants and they seriously affect water quality. In this study, we suggested that a novel multifunctional Ag3PO4 loaded hydroxyapatite (HAP) material can remove the typical pollutants from water. The Ag3PO4/HAP composites were synthesized facilely via in-situ precipitation of Ag3PO4 on the pre-existing HAP nanowires. By optimizing the composition of Ag3PO4 and HAP, the material could achieve an optimal photocatalytic activity to decompose rhodamine B (RhB), methyl orange (MO) and methylene blue (MB) under visible light irradiations with enhanced pH stability. Besides, the adsorption of Pb(II) on the Ag3PO4/HAP reached a maximum capacity of 250 mg/g and this value was approximately three times as that of pure HAP. Furthermore, the composite material exhibited excellent antibacterial activities towards gram-negative bacterium (Escherichia coli) and gram-positive bacterium (Stphylococcus aureus). The results highlighted the cooperative effect between Ag3PO4 and hydroxyapatite (HAP). The simultaneous removals of dyes, toxic metal ions, and bacteria with a high efficiency followed an easy approach for the purification of contaminated water via the rationally designed material, in which the Ag3PO4/HAP composite might be developed as a general water treatment material with multiple functions. PMID- 26150281 TI - Novel recycle technology for recovering rare metals (Ga, In) from waste light emitting diodes. AB - This work develops a novel process of recycling rare metals (Ga, In) from waste light-emitting diodes using the combination of pyrolysis, physical disaggregation methods and vacuum metallurgy separation. Firstly, the pure chips containing InGaN/GaN are adopted to study the vacuum separation behavior of rare metals, which aims to provide the theoretical foundation for recycling gallium and indium from waste light-emitting diodes. In order to extract the rare-metal-rich particles from waste light-emitting diodes, pyrolysis and physical disaggregation methods (crushing, screening, grinding and secondly screening) are studied respectively, and the operating parameters are optimized. With low boiling points and high saturation vapor pressures under vacuum, gallium and indium are separated from rare-metal-rich particles by the process of evaporation and condensation. By reference to the separating parameters of pure chips, gallium and indium in waste light-emitting diodes are recycled with the recovery efficiencies of 93.48% and 95.67% under the conditions as follows: heating temperature of 1373 K, vacuum pressure of 0.01-0.1 Pa, and holding time of 60 min. There are no secondary hazardous materials generated in the whole processes. This work provides an efficient and environmentally friendly process for recycling rare metals from waste light-emitting diodes. PMID- 26150282 TI - Chemical stabilisation of lead in shooting range soils with phosphate and magnesium oxide: Synchrotron investigation. AB - Three Australian shooting range soils were treated with phosphate and magnesium oxide, or a combination of both to chemically stabilize Pb. Lead speciation was determined after 1 month ageing by X-ray absorption spectroscopy combined with linear combination fitting in control and treated soils. The predominant Pb species in untreated soils were iron oxide bound Pb, humic acid bound Pb and the mineral litharge. Treatment with phosphate resulted in substantial pyromorphite formation in two of the soils (TV and PE), accounting for up to 38% of Pb species present, despite the addition of excess phosphate. In MgO treated soils only, up to 43% of Pb was associated with MgO. Litharge and Pb hydroxide also formed as a result of MgO addition in the soils. Application of MgO after P treatment increased hydroxypyromorphite/pyromorphite formation relative to soils teated with phosphate only. X-ray diffraction and Scanning electron microscopy revealed PbO precipitate on the surface of MgO. Soil pH, (5.3-9.3) was an important parameter, as was the solubility of existing Pb species. The use of direct means of determination of the stabilisation of metals such as by X-ray absorption spectroscopy is desirable, particularly in relation to understanding long term stability of the immobilised contaminants. PMID- 26150283 TI - Effect of neutralized solid waste generated in lime neutralization on the ferrous ion bio-oxidation process during acid mine drainage treatment. AB - Bio-oxidation of ferrous ions prior to lime neutralization exhibits great potential for acid mine drainage (AMD) treatment, while slow ferrous ion bio oxidation or total iron precipitation is a bottleneck in this process. In this study, neutralized solid waste (NSW) harvested in an AMD lime neutralization procedure was added as a crystal seed in AMD for iron oxyhydroxysulfate bio synthesis. The effect of this waste on ferrous ion oxidation efficiency, total iron precipitation efficiency, and iron oxyhydroxysulfate minerals yield during ferrous ion bio-oxidation by Acidithiobacillus ferrooxidans was investigated. Ferrous ion oxidation efficiency was greatly improved by adding NSW. After 72 h incubation, total iron precipitation efficiency in treatment with 24 g/L of NSW was 1.74-1.03 times higher than in treatment with 0-12 g/L of NSW. Compared with the conventional treatment system without added NSW, the iron oxyhydroxysulfate minerals yield was increased by approximately 21.2-80.9% when 3-24 g/L of NSW were added. Aside from NSW, jarosite and schwertmannite were the main precipitates during ferrous ion bio-oxidation with NSW addition. NSW can thus serve as the crystal seed for iron oxyhydroxysulfate mineral bio-synthesis in AMD, and improve ferrous ion oxidation and total iron precipitation efficiency significantly. PMID- 26150284 TI - [Occupational stress and myocardial infarction]. AB - Besides the best-known role of depressed mood, occupational stress deserves to be taken as a coronary risk factor. There are two basic models to define occupational stress: Karasek's model (high job psychological demands associated with low decision latitude, or even low social support at work) and Siegrist's model (imbalance between efforts and rewards received). The combination of the two models better reflects the coronary risk than each model alone. Occupational stress appears both as a risk factor and a prognostic factor after the occurrence of myocardial infarction. The relevance of the models is best in men or in younger age subjects. In women, role conflicts (occupational/domestic), the existence of excessive "intrinsic" efforts (job over investment) and association with marital stress provide more specific information. Burnout, particularly among health professionals, and bullying at work are also linked to cardiovascular risk. Occupational stress is a collective indicator of health at work, valuable to the employer. At an individual level, it can lead to therapeutic preventive approaches. PMID- 26150285 TI - The role of periostin in neoplastic processes. AB - Periostin, also called osteoblast-specific factor 2 (OSF-2), is a multifunctional glycoprotein that belongs to the group of matricellular proteins. Due to its characteristic molecular structure containing integrin-binding domains, periostin is capable of binding to multiple integrin receptors (alphavbeta3, alphavbeta5, alpha6beta4), thus affecting the regulation of the intracellular signaling pathways associated with protein kinases PI3K/AKT and focal adhesion kinase (FAK). This protein thus plays a role in the adhesion process, in the migration of many cells, and importantly, epithelial-mesenchymal transition of cancer cells. Periostin also participates in the processes of angiogenesis and lymphangiogenesis, metastases of cancer cells, and remodeling of the extracellular matrix. Increased expression of periostin has been observed in various tumor types, including breast, NSCLC, colorectal, pancreatic, prostate, and ovarian cancers, as well as tumors of the head and neck, and glioblastomas. Many groups have recently reported on periostin's key role in tumor progression, which suggests that periostin can be considered a potential therapeutic target. PMID- 26150286 TI - Increased skeletal muscle expression of VEGF induced by massage and exercise. AB - INTRODUCTION: Numerous investigations have been carried out to describe the role of massage in preparing for and restoring efficiency after physical exercise. Furthermore, vascular endothelial growth factor (VEGF) enhances blood vessel growth, and in effect contributes to the regeneration of tissues. Since its expression in active skeletal muscles has not been yet determined, the aim of this study was to investigate whether muscle massage performed before and during running exercise affects the expression of VEGF-A in muscles. MATERIAL AND METHODS: The study was carried out on 75 adult Buffalo rats subjected to running exercise training for 10 weeks. Rats were massaged prior (group PM) or during exercise (group M) or were not massaged (group C). The massage consisted of spiral movements along the plantar surface of flexor digitorum brevis muscle. After 1, 3, 5, 7 and 10 week of training, five rats from every group were anesthetized and immunohistochemistry, Western blot, and PCR analyses were performed on obtained muscle tissue to determine VEGF-A expression. RESULTS: After the first week of training, a significant increase of VEGF-A gene expression analyzed by qPCR in muscle tissue was observed in the PM group, whereas in the third week, the predominant growth of studied marker was seen in the M group. Increased VEGF-A expression on the protein level was observed in both massaged groups following the first week. A moderate positive correlation was found between the expression of the VEGF-A gene and protein in all experimental groups (r = 0.389). CONCLUSION: Short-term repeated massage may contribute to processes of creation of new and development of already existing vascular networks in the skeletal muscle tissue during increased exercise. PMID- 26150287 TI - Live imaging of beta-1,3-glucan synthase FKS-1 in Neurospora crassa hyphae. AB - The subcellular localization and dynamics of FKS-1, the putative catalytic subunit of the beta-1,3-glucan synthase complex, was analyzed in growing hyphae of Neurospora crassa by live confocal microscopy. GFP-tagged FKS-1 accumulated at the outer layer of the Spitzenkorper (Spk), and at the apical plasma membrane (PM). Fluorescence recovery after photobleaching analysis revealed arrival of FKS 1-containing carriers first at the immediate surroundings of the core region of the Spk, and thereafter to the Spk most outer region. The results obtained here and previous data suggest that FKS-1 is transported to the Spk in macrovesicles. PMID- 26150288 TI - Persistent homology and many-body atomic structure for medium-range order in the glass. AB - The characterization of the medium-range (MRO) order in amorphous materials and its relation to the short-range order is discussed. A new topological approach to extract a hierarchical structure of amorphous materials is presented, which is robust against small perturbations and allows us to distinguish it from periodic or random configurations. This method is called the persistence diagram (PD) and introduces scales to many-body atomic structures to facilitate size and shape characterization. We first illustrate the representation of perfect crystalline and random structures in PDs. Then, the MRO in amorphous silica is characterized using the appropriate PD. The PD approach compresses the size of the data set significantly, to much smaller geometrical summaries, and has considerable potential for application to a wide range of materials, including complex molecular liquids, granular materials, and metallic glasses. PMID- 26150289 TI - Discovery of N-aryl-naphthylamines as in vitro inhibitors of the interaction between HIV integrase and the cofactor LEDGF/p75. AB - A series of N-aryl-naphthylamines, exemplified by the structures 11-16, were chosen for an in-house library screening to assay their ability to disrupt the interaction between the LEDGF cofactor and the HIV integrase. Structure modification led also to design and synthesize new compounds 17a-f. Compounds 11e,h,k,n, 13b, and 14 showed good activity in AlphaScreen assay. The most active compound 11e (IC50 = 2.5 MUM) was selected for molecular modeling studies and showed a binding mode similar to the one of the known LEDGIN 8. PMID- 26150290 TI - Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review. AB - Hindered phenols find a wide variety of applications across many different industry sectors. Butylated hydroxytoluene (BHT) is a most commonly used antioxidant recognized as safe for use in foods containing fats, pharmaceuticals, petroleum products, rubber and oil industries. In the past two decades, there has been growing interest in finding novel antioxidants to meet the requirements of these industries. To accelerate the antioxidant discovery process, researchers have designed and synthesized a series of BHT derivatives targeting to improve its antioxidant properties to be having a wide range of antioxidant activities markedly enhanced radical scavenging ability and other physical properties. Accordingly, some structure-activity relationships and rational design strategies for antioxidants based on BHT structure have been suggested and applied in practice. We have identified 14 very sensitive parameters, which may play a major role on the antioxidant performance of BHT. In this review, we attempt to summarize the current knowledge on this topic, which is of significance in selecting and designing novel antioxidants using a well-known antioxidant BHT as a building-block molecule. Our strategy involved investigation on understanding the chemistry behind the antioxidant activities of BHT, whether through hydrogen or electron transfer mechanism to enable promising anti-oxidant candidates to be synthesized. PMID- 26150291 TI - Harnessing dark fermentative hydrogen from pretreated mixture of food waste and sewage sludge under sequencing batch mode. AB - Food waste and sewage sludge are the most abundant and problematic organic wastes in any society. Mixture of these two wastes may provide appropriate substrate condition for dark fermentative biohydrogen production based on synergistic mutual benefits. This work evaluates continuous hydrogen production from the cosubstrate of food waste and sewage sludge to verify mechanisms of performance improvement in anaerobic sequencing batch reactors. Volatile solid concentration and mixing ratio of food waste and sludge were adjusted to 5 % and 80:20, respectively. Five different hydraulic retention times (HRT) of 36, 42, 48, 72, and 108 h were tested using anaerobic sequencing batch reactors to find out optimal operating condition. Results show that the best performance was achieved at HRT 72 h, where the hydrogen yield, the hydrogen production rate, and hydrogen content were 62.0 mL H2/g VS, 1.0 L H2/L/day, and ~50 %, respectively. Sufficient solid retention time (143 h) and proper loading rate (8.2 g COD/L/day as carbohydrate) at HRT 72h led to the enhanced performance with better hydrogen production showing appropriate n-butyrate/acetate (B/A) ratio of 2.6. Analytical result of terminal-restriction fragment length polymorphism revealed that specific peaks associated with Clostridium sp. and Bacillus sp. were strongly related to enhanced hydrogen production from the cosubstrate of food waste and sewage sludge. PMID- 26150292 TI - Effects of liquid layers and distribution patterns on three-phase saturation and relative permeability relationships: a micromodel study. AB - In the current study, we used micromodel experiments to study three-phase fluid flow in porous media. In contrast to previous studies, we simultaneously observed and measured pore-scale fluid behavior and three-phase constitutive relationships with digital image acquisition/analysis, fluid pressure control, and permeability assays. Our results showed that the fluid layers significantly influenced pore scale, three-phase fluid displacement as well as water relative permeability. At low water saturation, water relative permeability not only depended on water saturation but also on the distributions of air and diesel. The results also indicate that the relative permeability-saturation model proposed by Parker et al. (1987) could not completely describe the experimental data from our three phase flow experiments because these models ignore the effects of phase distribution. A simple bundle-of-tubes model shows that the water relative permeability was proportional to the number of apparently continuous water paths before the critical stage in which no apparently continuous water flow path could be found. Our findings constitute additional information about the essential constitutive relationships involved in both the understanding and the modeling of three-phase flows in porous media. PMID- 26150293 TI - Do antibiotics have environmental side-effects? Impact of synthetic antibiotics on biogeochemical processes. AB - Antibiotic use in the early 1900 vastly improved human health but at the same time started an arms race of antibiotic resistance. The widespread use of antibiotics has resulted in ubiquitous trace concentrations of many antibiotics in most environments. Little is known about the impact of these antibiotics on microbial processes or "non-target" organisms. This mini-review summarizes our knowledge of the effect of synthetically produced antibiotics on microorganisms involved in biogeochemical cycling. We found only 31 articles that dealt with the effects of antibiotics on such processes in soil, sediment, or freshwater. We compare the processes, antibiotics, concentration range, source, environment, and experimental approach of these studies. Examining the effects of antibiotics on biogeochemical processes should involve environmentally relevant concentrations (instead of therapeutic), chronic exposure (versus acute), and monitoring of the administered antibiotics. Furthermore, the lack of standardized tests hinders generalizations regarding the effects of antibiotics on biogeochemical processes. We investigated the effects of antibiotics on biogeochemical N cycling, specifically nitrification, denitrification, and anammox. We found that environmentally relevant concentrations of fluoroquinolones and sulfonamides could partially inhibit denitrification. So far, the only documented effects of antibiotic inhibitions were at therapeutic doses on anammox activities. The most studied and inhibited was nitrification (25-100 %) mainly at therapeutic doses and rarely environmentally relevant. We recommend that firm conclusions regarding inhibition of antibiotics at environmentally relevant concentrations remain difficult due to the lack of studies testing low concentrations at chronic exposure. There is thus a need to test the effects of these environmental concentrations on biogeochemical processes to further establish the possible effects on ecosystem functioning. PMID- 26150294 TI - Synergetic effects of Sr-doped CuBi2O4 catalyst with enhanced photoactivity under UVA- light irradiation. AB - Sr-doped CuBi2O4 micro-particles were successively synthesized via a solid-state technique and were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and UV-vis diffuse reflectance spectroscopy (UV-vis-DRS) techniques. Results show that Sr-doped CuBi2O4 was crystallized with a spinel-type structure and tetragonal crystal system, and the band gap energy was about 1.35 eV. The as-prepared Sr-doped CuBi2O4 treated at 573 degrees C for 12 h exhibited the highest efficiency, as a result of 97.22 % of CR degradation within 220 min, which is approximately 31 times greater than CR photodegradation when catalyzed by CuBi2O4 (3.13 %) and about 2.3 times superior than that catalyzed by the untreated Sr-doped CuBi2O4 sample (42.08 %). Pseudo-first-order kinetic model gave the best fit, with highest correlation coefficients (R (2) = 0.94-0.97). The Sr-doping and extending reaction time up to 12 h could be effective in producing Sr-doped CuBi2O4 materials that delay electron-hole recombination, thereby increasing the lifetime of the electron electron-hole separation and support the charge carrier transfer to the catalyst surface. On the basis of the calculated energy band positions, superoxide radical anions (O2 (*-)) were the main oxidative species responsible for the photocatalytic degradation of CR dye solution. PMID- 26150295 TI - Use of food waste as fish feeds: effects of prebiotic fibers (inulin and mannanoligosaccharide) on growth and non-specific immunity of grass carp (Ctenopharyngodon idella). AB - The effects of inulin and mannanoligosaccharide (MOS) on the growth performance and non-specific immunity of grass carp were studied. Two doses of prebiotic fiber with 0.2 or 2% of the fibers are being mixed into fish feed pellets. Fish growth as well as selected non-specific immune parameters of grass carp were tested in a feeding trial, which lasted for 8 weeks. Fish was fed at 2.5% body mass per day. INU02, INU2, and MOS2 significantly improved relative weight gain, specific growth rate, protein efficiency ratio, and food conversion ratio of grass carp fed with food waste-based diet. In terms of non-specific immune response, grass carp showed significant improvement in all three tested parameters (total serum immunoglobin, bactericidal activity, and anti-protease activity). Adding 2% of inulin (INU2) into food waste diets seemed to be more preferable than other supplemented experimental diets (INU02, MOS02, MOS2), as it could promote growth of grass carp as well as improving the non-specific immune systems of grass carp. PMID- 26150297 TI - Microcystin accumulation in bighead carp (Aristichthys nobilis) during a Microcystis-dominated bloom and risk assessment of the dietary intake in a fish pond in China. AB - Microcystins (MCs) produced by cyanobacteria can accumulate in freshwater fish tissues and pose potential risk to human health. In this study, variations in MC content were examined in water samples and fish tissues during a Microcystis aeruginosa-dominated bloom in a fish pond in China, from June 2009 to August 2009. A total of ten microcystin variants were detected in water samples in the fish pond, including MCLR, MCRR, MCYR, MCLF, MCLY, MCLA, and MCLW, and other three undefined MC variants. MCLR was the dominant variant in the water samples, followed by MCLF and MCLY. The highest MC concentration in the common carp (Aristichthys nobilis) was found in the order intestine > spleen > muscle; however, the order with the most MC variants detected was muscle > spleen = kidney = gallbladder > liver = intestine. The highest overall MC concentration detected in the water samples was 12.24 MUg L-1, and the estimated daily intake for humans from the consumption of fish was about 0.48 MUg MCLR eq kg-1 body weight (BW), 12-fold the tolerable daily intake (TDI) proposed by the World Health Organization. Therefore, the combined risks from skin exposure and food intake in this fish pond should not be overlooked. PMID- 26150296 TI - Effects of bisphenol A, an environmental endocrine disruptor, on the endogenous hormones of plants. AB - Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical in the environment that exerts potential harm to plants. Phytohormones play important roles both in regulating multiple aspects of plant growth and in plants' responses to environmental stresses. But how BPA affects plant growth by regulating endogenous hormones remains poorly understood. Here, we found that treatment with 1.5 mg L(-1) BPA improved the growth of soybean seedlings, companied by increases in the contents of indole-3-acetic acid (IAA) and zeatin (ZT), and decreases in the ratios of abscisic acid (ABA)/IAA, ABA/gibberellic acid (GA), ABA/ZT, ethylene (ETH)/GA, ETH/IAA, and ETH/ZT. Treatment with higher concentrations of BPA (from 3 to 96 mg L(-1)) inhibited the growth of soybean seedlings, meanwhile, decreased the contents of IAA, GA, ZT, and ETH, and increased the content of ABA and the ratios of ABA/IAA, ABA/GA, ABA/ZT, ETH/GA, ETH/IAA, and ETH/ZT. The increases in the ratios of growth and stress hormones were correlated with the increase in the BPA content of the roots. Thus, BPA could affect plant growth through changing the levels of single endogenous hormone and the ratios of growth and stress hormones in the roots because of BPA absorption by the roots. PMID- 26150298 TI - Occurrence and distribution of endocrine-disrupting compounds in the Honghu Lake and East Dongting Lake along the Central Yangtze River, China. AB - Lakes along the Yangzte River are very important for inhabitants due to their ecosystem service values. In this study, the level of eight endocrine-disrupting compounds (EDCs) was studied in the Honghu Lake and East Dongting Lake. In each lake, 21 water samples and 21 sediment samples were collected. The total concentrations of eight EDCs in surface water (47.60-419.82 ng L(-1), mean value: 225.65 ng L(-1)) and sediments (202.71-635.36 ng g(-1) dry weight (dw), mean value 371.90 ng g(-1) dw) of Honghu Lake were significantly higher than those in surface water (43.52-394.21 ng L(-1), mean value 153.03 ng L(-1)) and sediment (70.01-464.63 ng g(-1) dw, mean value 238.42 ng g(-1) dw) in East Dongting Lake. 4-Nonylphenol (NP), 4-octylphenol (OP), and bisphenol A (BPA) in surface water and sediments were main EDCs in two lakes. No correlation relationships were found between concentrations of EDCs in water and sediment from two lakes. The concentrations of OP and 17alpha-ethinylestradiol (EE2) in sediments of Honghu Lake had significant positive correlation with the content of total organic carbon (TOC). The concentrations of EDCs in outlet of Honghu Lake were comparable to those in the main lake, whereas the EDCs in outlet of East Dongting Lake were lower than those in the main lake. The EDCs in Honghu Lake and East Dongting Lake may have a significant potential biological effect on fish based on the estimation of EDC estrogenicity. PMID- 26150299 TI - Quantitative Collection and Enzymatic Activity of Glucose Oxidase Nanotubes Fabricated by Templated Layer-by-Layer Assembly. AB - We report on the fabrication of enzyme nanotubes in nanoporous polycarbonate membranes via the layer-by-layer (LbL) alternate assembly of polyethylenimine (PEI) and glucose oxidase (GOX), followed by dissolution of the sacrificial template in CH2Cl2, collection, and final dispersion in water. An adjuvant assisted filtration methodology is exploited to extract quantitatively the nanotubes without loss of activity and morphology. Different water-soluble CH2Cl2 insoluble adjuvants are tested for maximal enzyme activity and nanotube stability; whereas NaCl disrupts the tubes by screening electrostatic interactions, the high osmotic pressure created by fructose also contributes to loosening the nanotubular structures. These issues are solved when using neutral, high molar mass dextran. The enzymatic activity of intact free nanotubes in water is then quantitatively compared to membrane-embedded nanotubes, showing that the liberated nanotubes have a higher catalytic activity in proportion to their larger exposed surface. Our study thus discloses a robust and general methodology for the fabrication and quantitative collection of enzymatic nanotubes and shows that LbL assembly provides access to efficient enzyme carriers for use as catalytic swarming agents. PMID- 26150300 TI - Activity cliffs and activity cliff generators based on chemotype-related activity landscapes. AB - Activity cliffs have large impact in drug discovery; therefore, their detection and quantification are of major importance. This work introduces the metric activity cliff enrichment factor and expands the previously reported activity cliff generator concept by adding chemotype information to representations of the activity landscape. To exemplify these concepts, three molecular databases with multiple biological activities were characterized. Compounds in each database were grouped into chemotype classes. Then, pairwise comparisons of structure similarities and activity differences were calculated for each compound and used to construct chemotype-based structure-activity similarity (SAS) maps. Different landscape distributions among four major regions of the SAS maps were observed for different subsets of molecules grouped in chemotypes. Based on this observation, the activity cliff enrichment factor was calculated to numerically detect chemotypes enriched in activity cliffs. Several chemotype classes were detected having major proportion of activity cliffs than the entire database. In addition, some chemotype classes comprising compounds with smooth structure activity relationships (SAR) were detected. Finally, the activity cliff generator concept was applied to compounds grouped in chemotypes to extract valuable SAR information. PMID- 26150301 TI - Phosphoinositide signaling in cancer: INPP4B Akt(s) out. AB - INPP4B acts as a tumor suppressor in various epithelial cancers by inhibiting PI3K/Akt signaling. Unexpectedly, tumor-promoting features of INPP4B in leukemia and breast cancer have been recently uncovered. In this spotlight, we discuss the seemingly paradoxical nature of INPP4B-mediated signaling in cancer. PMID- 26150302 TI - The effect of ego-motion on environmental monitoring. AB - Air pollution has a proven impact on public health. Currently, pollutant levels are obtained by high-priced, sizeable, stationary Air Quality Monitoring (AQM) stations. Recent developments in sensory and communication technologies have made relatively low-cost, micro-sensing units (MSUs) feasible. Their lower power consumption and small size enable mobile sensing, deploying single or multiple units simultaneously. Recent studies have reported on measurements acquired by mobile MSUs, mounted on cars, bicycles and pedestrians. While these modes of transportation inherently present different velocity and acceleration regimes, the effect of the sensors' varying movement characteristics have not been previously accounted for. This research assesses the impact of sensor's motion on its functionality through laboratory measurements and a field campaign. The laboratory setup consists of a wind tunnel to assess the effect of air flow on the measurements of nitrogen dioxide and ozone at different velocities in a controlled environment, while the field campaign is based on three cars mounted with MSUs, measuring pollutants and environmental variables at different traveling speeds. In both experimental designs we can regard the MSUs as a moving object in the environment, i.e. having a distinct ego-motion. The results show that MSU's behavior is highly affected by variation in speed and sensor placement with respect to direction of movement, mainly due to the physical properties of installed sensors. This strongly suggests that any future design of MSU must account for the speed effect from the design stage all the way through deployment and results analysis. This is the first report examining the influence of airflow variations on MSU's ability to accurately measure pollutant levels. PMID- 26150303 TI - Using stable isotopes in tracing contaminant sources in an industrial area: A case study on the hydrological basin of the Olt River, Romania. AB - Tracing pollution sources and transformation of nitrogen compounds in surface- and groundwater is an issue of great significance worldwide due to the increased human activity, translated in high demand of water resources and pollution. In this work, the hydrological basin of an important chemical industrial platform in Romania (Ramnicu Valcea industrial area) was characterized in terms of the physico-chemical and isotope composition of delta(18)O and delta(2)H in water samples and delta(15)N of the inorganic nitrogen species. Throughout a period of one year, water samples from the Olt River and its more important tributaries were collected monthly in the industrial area, when the seasonal and spatial isotope patterns of the surface waters and the main sources of pollution were determined. Higher inorganic nitrogen concentrations (up to 10.2 mg N L(-1)) were measured between November 2012 and April 2013, which were designated as anthropogenic additions using the mixing calculations. The main sources of pollution with inorganic nitrogen were agriculture and residential release. The inorganic nitrogen from the industrial waste water duct had a distinct delta(15)N fingerprint (mean of -8.60/00). Also, one industrial release into the environment was identified for Olt River, at Ionesti site, in November 2012. The mean precipitation samples had the lowest inorganic nitrogen concentrations (less than 5.5 mg N L(-1)) with a distinct delta(15)N fingerprint compared to the surface and industrial waters. PMID- 26150304 TI - The drinking water treatment process as a potential source of affecting the bacterial antibiotic resistance. AB - Two waterworks, with source water derived from the Huangpu or Yangtze River in Shanghai, were investigated, and the effluents were plate-screened for antibiotic resistant bacteria (ARB) using five antibiotics: ampicillin (AMP), kanamycin (KAN), rifampicin (RFP), chloramphenicol (CM) and streptomycin (STR). The influence of water treatment procedures on the bacterial antibiotic resistance rate and the changes that bacteria underwent when exposed to the five antibiotics at concentration levels ranging from 1 to 100 MUg/mL were studied. Multi-drug resistance was also analyzed using drug sensitivity tests. The results indicated that bacteria derived from water treatment plant effluent that used the Huangpu River rather than the Yangtze River as source water exhibited higher antibiotic resistance rates against AMP, STR, RFP and CM but lower antibiotic resistance rates against KAN. When the antibiotic concentration levels ranged from 1 to 10 MUg/mL, the antibiotic resistance rates of the bacteria in the water increased as water treatment progressed. Biological activated carbon (BAC) filtration played a key role in increasing the antibiotic resistance rate of bacteria. Chloramine disinfection can enhance antibiotic resistance. Among the isolated ARB, 75% were resistant to multiple antibiotics. Ozone oxidation, BAC filtration and chloramine disinfection can greatly affect the relative abundance of bacteria in the community. PMID- 26150305 TI - Preparation of a specific bamboo based activated carbon and its application for ciprofloxacin removal. AB - The studied bamboo based activated carbon (BbAC) with high specific surface area (SSA) and high micro pore volume was prepared from bamboo scraps by the combined activation of H3PO4 and K2CO3. The BbAC was characterized based on the N2 adsorption isotherm at 77K. The results showed that the SSA and pore volume of BbAC increased with increasing impregnation ratio and reached maxima at the impregnation ratio of 3:1 at 750 degrees C. Under these optimal conditions, the BbAC obtained could have a maximum SSA of 2237 m(2)/g and a maximum total pore volume of 1.23 cm(3)/g with the micro pore ratio of more than 90%. The adsorption performance of ciprofloxacin (CIP) on the BbAC was determined at 298 K. The Langmuir and Freundlich models were employed to describe the adsorption equilibrium and the kinetic data were fitted by pseudo first-order and pseudo second-order kinetic models. The results showed that the Langmuir model and the pseudo second-order kinetic model presented better fittings for the adsorption equilibrium and kinetics data, respectively. The maximum adsorption amount of CIP (613 mg/g) on the BbAC was much higher than the report in the literature. Conclusively, the BbAC could be a promising adsorption material for CIP removal from water. PMID- 26150306 TI - Effects of fungicides on decomposer communities and litter decomposition in vineyard streams. AB - Large amounts of fungicides are applied globally and partly enter freshwater ecosystems. A few laboratory studies examined their effects on decomposer communities and the ecosystem process of litter decomposition (LD), whereas the field situation remains largely unknown. We conducted a field study with 17 stream sites in a German vineyard area where fungicides represent the dominant pest control agent. Passive samplers were used to monitor 15 fungicides and 4 insecticides in streams and their toxicity was described using the toxic unit approach, whereas sediment samples were taken to characterise total copper concentrations. Microbial and leaf-shredding invertebrate community composition and related LD rates were assessed at each site. The structure of microbial and shredder communities as well as fungal biomass changed along the fungicide toxicity gradient. The changes in microbial endpoints were associated with a reduction of microbial LD rate of up to 40% in polluted streams. By contrast, neither the invertebrate LD rate nor in-situ measured gammarid feeding rates correlated with fungicide toxicity, but both were negatively associated with sediment copper concentrations. A subsequent laboratory experiment employing field fungicide concentrations suggested that the microbial community changes are causal. Overall, our results suggest that fungicides can affect LD under field conditions. PMID- 26150307 TI - Contrasting controls on the phosphorus concentration of suspended particulate matter under baseflow and storm event conditions in agricultural headwater streams. AB - Whilst the processes involved in the cycling of dissolved phosphorus (P) in rivers have been extensively studied, less is known about the mechanisms controlling particulate P concentrations during small and large flows. This deficiency is addressed through an analysis of large numbers of suspended particulate matter (SPM) samples collected under baseflow (n=222) and storm event (n=721) conditions over a 23-month period across three agricultural headwater catchments of the River Wensum, UK. Relationships between clay mineral and metal oxyhydroxide associated elements were assessed and multiple linear regression models for the prediction of SPM P concentration under baseflow and storm event conditions were formulated. These models, which explained 71-96% of the variation in SPM P concentration, revealed a pronounced shift in P association from iron (Fe) dominated during baseflow conditions to particulate organic carbon (POC) dominated during storm events. It is hypothesised this pronounced transition in P control mechanism, which is consistent across the three study catchments, is driven by changes in SPM source area under differing hydrological conditions. In particular, changes in SPM Fe-P ratios between small and large flows suggest there are three distinct sources of SPM Fe; surface soils, subsurface sediments and streambed iron sulphide. Further examination of weekly baseflow data also revealed seasonality in the Fe-P and aluminium oxalate-dithionate (Alox-Aldi) ratios of SPM, indicating temporal variability in sediment P sorption capacity. The results presented here significantly enhance our understanding of SPM P associations with soil derived organic and inorganic fractions under different flow regimes and has implications for the mitigation of P originating from different sources in agricultural catchments. PMID- 26150308 TI - Ecotoxicological assessment of soil microbial community tolerance to glyphosate. AB - Glyphosate is the most used herbicide worldwide. While contrasting results have been observed related with its impact on soil microbial communities, more studies are necessary to elucidate the potential effects of the herbicide. Differences in tolerance detected by Pollution Induced Community Tolerance (PICT) approach could reflect these effects. The objective of the present study was to assess the tolerance to glyphosate (the active ingredient and a commercial formulation) of contrasting soils with (H) and without (NH) history of exposure. The hypothesis of a higher tolerance in H soils due to a sustained selection pressure on community structure was tested through the PICT approach. Results indicated that tolerance to glyphosate is not consistent with previous history of exposure to the herbicide either for the active ingredient or for a commercial formulation. Soils of H and NH sites were also characterized in order to determine to what extent they differ in their functional diversity and structure of microbial communities. Denaturant Gradient Gel Electrophoresis (DGGE) and Quantitative Real Time PCR (Q-PCR) indicated high similarity of Eubacteria profiles as well as no significant differences in abundance, respectively, between H and NH sites. Community level physiological profiling (CLPP) indicated some differences in respiration of specific sources but functional diversity was very similar as reflected by catabolic evenness (E). These results support PICT assay, which ideally requires soils with differences in their exposure to the contaminant but minor differences in other characteristics. This is, to our knowledge, the first report of PICT approach with glyphosate examining tolerance at soil microbial community level. PMID- 26150309 TI - Obsessive-compulsive symptoms among alcoholics in outpatient treatment: Prevalence, severity and correlates. AB - The literature on symptoms of obsessive-compulsive disorder (OCD) in alcoholic patients is scarce and such symptoms can go unnoticed, worsening the prognosis of alcoholism. The objectives were to estimate the prevalence and severity of obsessive-compulsive symptoms in alcoholics undergoing outpatient treatment and to assess sociodemographic and clinical correlates, including suicidal behaviors. The instruments used in this cross-sectional study were the Obsessive-Compulsive Inventory - Revised (OCI-R), the Short Alcohol Dependence Data and the Beck Depression Inventory. After descriptive analyses, bivariate analyses between the categorical ("probable OCD": OCI-R>=27) and dimensional (OCI-R total and subscales scores) outcomes and all explanatory variables were conducted. Eleven (20.4%) of the 54 alcoholic patients (37 men and 17 women) presented "probable OCD", which was associated with lower income, more severe dependence, depression, lifetime suicidal thoughts and plans and suicide attempts. OCI-R severity (mean 16.0) was associated with the same predictors and with psychiatric hospitalization. Suicidal behaviors were mainly associated with the Obsession, Hoarding and Washing subscales. It is essential to investigate and treat OCD symptoms in alcoholics, as they are associated with greater severity of dependence, depression and suicidal behaviors. Longitudinal studies are required to assess the impact of OCD treatment on the clinical course of alcoholism. PMID- 26150311 TI - ImageJ analysis of dentin tubule distribution in human teeth. AB - Mapping the distribution of dentin tubules is vital to understanding the structure-function relationship of dentin, an important indicator of tooth stability. This study compared the distances between and density of tubules in the external dentin located in the crown region of an adult human incisor and molar to determine if analysis could be conducted using light-level microscopy. Teeth were processed for routine histology, cut in cross-section, images captured using Advanced SPOT Program, and microstructure was analyzed using ImageJ (NIH). Intratubular (peritubular) dentin with or without odontoblast processes were observed and although incisor and molar images appeared visually similar, plot profile graphs differed. Distance-intervals between tubules in the incisor (5.45 7.67 MUm) had an overall range of 2.22 MUm and in the molar (7.43-8.42 MUm) an overall range of 0.99 MUm. While molar tubule distribution displayed a tighter overall range, there was a smaller distance between most incisor tubules. The average densities observed in incisors were 15,500 tubules/mm(2), compared with 20,100 tubules/mm(2) in molars. ImageJ analysis of prepared histology microscopic slides provides researchers with a rapid, inexpensive assessment tool when compared with advanced/ultrastructural methodologies. By combining routine histological processing and light microscopic observations followed by ImageJ analysis, tooth structure can be converted into numerical data and easily mastered by laboratory personnel. PMID- 26150310 TI - Automated identification of keratinization and keratin pearl area from in situ oral histological images. AB - Oral squamous cell carcinoma (OSCC) has contributed 90% of oral cancer worldwide. In situ histological evaluation of tissue sections is the gold standard for oral cancer detection. Formation of keratinization and keratin pearl is one of the most important histological features for OSCC grading. This paper aims at developing a computer assisted quantitative microscopic methodology for automated identification of keratinization and keratin pearl area from in situ oral histological images. The proposed methodology includes colour space transform in YDbDr channel, enhancement of keratinized area in most significant bit (MSB) plane of Db component, segmentation of keratinized area using Chan-Vese model. The proposed methodology achieves 95.08% segmentation accuracy in comparison with (manually) experts-based ground truths. In addition, a grading index describing keratinization area is explored for grading OSCC cases (poorly, moderately and well differentiated). PMID- 26150312 TI - The low frequency modes of solvated ions and ion pairs in aqueous electrolyte solutions: iron(ii) and iron(iii) chloride. AB - We have investigated the hydration dynamics of solvated iron(ii) and iron(iii) chloride. For this, THz/FIR absorption spectra of acidified aqueous FeCl2 and FeCl3 solutions have been measured in a frequency range of 30-350 cm(-1) (~1-10 THz). We observe a nonlinear concentration dependence of the absorption, which is attributed to the progressive formation of chloro-complexes of Fe(ii) and Fe(iii), respectively. By principal component analysis of the concentration dependent absorption spectra, we deduced the molar extinction spectra of the solvated species Fe(2+) + 2Cl(-) and FeCl(+) + Cl(-), as well as FeCl(2+) + 2Cl( ) and FeCl2(+) + Cl(-). In addition, we obtain ion association constants log KFeCl2 = -0.88(5) and log KFeCl3 = -0.32(16) for the association of Fe(2+) and Cl(-) to FeCl(+) and the association of FeCl(2+) and Cl(-) to FeCl2(+), respectively. We performed a simultaneous fit of all the effective extinction spectra and their differences, including our previous results of solvated manganese(ii) and nickel(ii) chlorides and bromides. Thereby we were able to assign absorption peaks to vibrational modes of ion-water complexes. Furthermore, we were able to estimate a minimum number of affected water molecules, ranging from ca. 7 in the case of FeCl(+) + Cl(-) to ca. 21 in the case of FeCl(2+) + Cl( ). PMID- 26150314 TI - Public health promotion of "local food": Constituting the self-governing citizen consumer. AB - This article explores how the recent and growing promotion of local foods by public health units in Ontario, Canada, rhetorically interpellates the "good" health citizen as someone who not only takes responsibility for personal health but, through the consumption and support of "local food," also accepts and fulfills her responsibilities to care for the local economy, the community's well being, and the natural environment. Drawing on Charland's concept of constitutive rhetoric, we analyze a selection of public health unit documents about local food to develop a textured account of the complex, multifaceted forms of health citizenship they constitute. Our analysis reveals that, despite their appeals to environmental sustainability and community well-being, these materials primarily characterize the ideal health citizen as an informed consumer who supports the interests of the neoliberal state through individualized lifestyle behaviors, consuming goods produced and distributed through private enterprise. By exhorting individuals to "buy local," public health discourse therefore frames responsible health citizenship principally in consumerist terms that constrain the range of available options for citizens to engage in meaningful action vis-a-vis their food systems. PMID- 26150313 TI - Transcriptome analysis of mRNA and miRNA in skeletal muscle indicates an important network for differential Residual Feed Intake in pigs. AB - Feed efficiency (FE) can be measured by feed conversion ratio (FCR) or residual feed intake (RFI). In this study, we measured the FE related phenotypes of 236 castrated purebred Yorkshire boars, and selected 10 extreme individuals with high and low RFI for transcriptome analysis. We used RNA-seq analyses to determine the differential expression of genes and miRNAs in skeletal muscle. There were 99 differentially expressed genes identified (q <= 0.05). The down-regulated genes were mainly involved in mitochondrial energy metabolism, including FABP3, RCAN, PPARGC1 (PGC-1A), HK2 and PRKAG2. The up-regulated genes were mainly involved in skeletal muscle differentiation and proliferation, including IGF2, PDE7A, CEBPD, PIK3R1 and MYH6. Moreover, 15 differentially expressed miRNAs (|log2FC| >= 1, total reads count >= 20, p <= 0.05) were identified. Among them, miR-136, miR-30e 5p, miR-1, miR-208b, miR-199a, miR-101 and miR-29c were up-regulated, while miR 215, miR-365-5p, miR-486, miR-1271, miR-145, miR-99b, miR-191 and miR-10b were down-regulated in low RFI pigs. We conclude that decreasing mitochondrial energy metabolism, possibly through AMPK - PGC-1A pathways, and increasing muscle growth, through IGF-1/2 and TGF-beta signaling pathways, are potential strategies for the improvement of FE in pigs (and possibly other livestock). This study provides new insights into the molecular mechanisms that determine RFI and FE in pigs. PMID- 26150315 TI - Targeting Neuronal Networks with Combined Drug and Stimulation Paradigms Guided by Neuroimaging to Treat Brain Disorders. AB - Improved therapy of brain disorders can be achieved by focusing on neuronal networks, utilizing combined pharmacological and stimulation paradigms guided by neuroimaging. Neuronal networks that mediate normal brain functions, such as hearing, interact with other networks, which is important but commonly neglected. Network interaction changes often underlie brain disorders, including epilepsy. "Conditional multireceptive" (CMR) brain areas (e.g., brainstem reticular formation and amygdala) are critical in mediating neuroplastic changes that facilitate network interactions. CMR neurons receive multiple inputs but exhibit extensive response variability due to milieu and behavioral state changes and are exquisitely sensitive to agents that increase or inhibit GABA-mediated inhibition. Enhanced CMR neuronal responsiveness leads to expression of emergent properties--nonlinear events--resulting from network self-organization. Determining brain disorder mechanisms requires animals that model behaviors and neuroanatomical substrates of human disorders identified by neuroimaging. However, not all sites activated during network operation are requisite for that operation. Other active sites are ancillary, because their blockade does not alter network function. Requisite network sites exhibit emergent properties that are critical targets for pharmacological and stimulation therapies. Improved treatment of brain disorders should involve combined pharmacological and stimulation therapies, guided by neuroimaging, to correct network malfunctions by targeting specific network neurons. PMID- 26150316 TI - Deep Brain Stimulation: More Complex than the Inhibition of Cells and Excitation of Fibers. AB - High-frequency deep brain stimulation (DBS) is an effective treatment for some movement disorders. Though mechanisms underlying DBS are still unclear, commonly accepted theories include a "functional inhibition" of neuronal cell bodies and the excitation of axonal projections near the electrodes. It is becoming clear, however, that the paradoxical dissociation "local inhibition" and "distant excitation" is far more complex than initially thought. Despite an initial increase in neuronal activity following stimulation, cells are often unable to maintain normal ionic concentrations, particularly those of sodium and potassium. Based on currently available evidence, we proposed an alternative hypothesis. Increased extracellular concentrations of potassium during DBS may change the dynamics of both cells and axons, contributing not only to the intermittent excitation and inhibition of these elements but also to interrupt abnormal pathological activity. In this article, we review mechanisms through which high extracellular potassium may mediate some of the effects of DBS. PMID- 26150317 TI - Enhanced flavor-nutrient conditioning in obese rats on a high-fat, high carbohydrate choice diet. AB - Through flavor-nutrient conditioning rats learn to prefer and increase their intake of flavors paired with rewarding, postingestive nutritional consequences. Since obesity is linked to altered experience of food reward and to perturbations of nutrient sensing, we investigated flavor-nutrient learning in rats made obese using a high fat/high carbohydrate (HFHC) choice model of diet-induced obesity (ad libitum lard and maltodextrin solution plus standard rodent chow). Forty rats were maintained on HFHC to induce substantial weight gain, and 20 were maintained on chow only (CON). Among HFHC rats, individual differences in propensity to weight gain were studied by comparing those with the highest proportional weight gain (obesity prone, OP) to those with the lowest (obesity resistant, OR). Sensitivity to postingestive food reward was tested in a flavor-nutrient conditioning protocol. To measure initial, within-meal stimulation of flavor acceptance by post-oral nutrient sensing, first, in sessions 1-3, baseline licking was measured while rats consumed grape- or cherry-flavored saccharin accompanied by intragastric (IG) water infusion. Then, in the next three test sessions they received the opposite flavor paired with 5 ml of IG 12% glucose. Finally, after additional sessions alternating between the two flavor-infusion contingencies, preference was measured in a two-bottle choice between the flavors without IG infusions. HFHC-OP rats showed stronger initial enhancement of intake in the first glucose infusion sessions than CON or HFHC-OR rats. OP rats also most strongly preferred the glucose-paired flavor in the two-bottle choice. These differences between OP versus OR and CON rats suggest that obesity is linked to responsiveness to postoral nutrient reward, consistent with the view that flavor nutrient learning perpetuates overeating in obesity. PMID- 26150318 TI - Proportional recovery after stroke depends on corticomotor integrity. AB - OBJECTIVE: For most patients, resolution of upper limb impairment during the first 6 months poststroke is 70% of the maximum possible. We sought to identify candidate mechanisms of this proportional recovery. We hypothesized that proportional resolution of upper limb impairment depends on ipsilesional corticomotor pathway function, is mirrored by proportional recovery of excitability in this pathway, and is unaffected by upper limb therapy dose. METHODS: Upper limb impairment was measured in 93 patients at 2, 6, 12, and 26 weeks after first-ever ischemic stroke. Motor evoked potentials (MEPs) and motor threshold were recorded from extensor carpi radialis using transcranial magnetic stimulation, and fractional anisotropy (FA) in the posterior limbs of the internal capsules was determined with diffusion-weighted magnetic resonance imaging. RESULTS: Initial impairment score, presence of MEPs and FA asymmetry were the only predictors of impairment resolution, indicating a key role for corticomotor tract function. By 12 weeks, upper limb impairment resolved by 70% in patients with MEPs regardless of their initial impairment, and ipsilesional rest motor threshold also resolved by 70%. Resolution of impairment was insensitive to upper limb therapy dose. INTERPRETATION: These findings indicate that upper limb impairment resolves by 70% of the maximum possible, regardless of initial impairment, but only for patients with intact corticomotor function. Impairment resolution seems to reflect spontaneous neurobiological processes that involve the ipsilesional corticomotor pathway. A better understanding of these mechanisms could lead to interventions that increase resolution of impairment above 70%. PMID- 26150319 TI - Transcription regulates HIF-1alpha expression in CD4(+) T cells. AB - The transcription factor hypoxia inducible factor-1alpha (HIF-1alpha) mediates the metabolic adaptation of cells to hypoxia and T-helper cell fate. However, HIF 1alpha regulation in CD4(+) T cells (T cells) remains elusive. Here we observed that depletion of oxygen (O2?2%) alone was not sufficient to induce HIF-1alpha expression in T cells. However, when hypoxic T cells were stimulated, HIF-1alpha was expressed and this was dependent on nuclear factor-kappaB- and nuclear factor of activated T cell (NFAT)-mediated transcriptional upregulation of Hif-1alpha mRNA. HIF-1alpha upregulation could be blocked by drugs inhibiting NF-kappaB, NFAT or mammalian target of rapamycin precluding CD4(+) T-cell stimulation or translation in T cells, as well as by blocking transcription. CD3, CD28, phorbol 12-myristat-13-acetat (PMA) or ionomycin-stimulated T cells did not express HIF 1alpha under normoxic conditions. In conclusion, regulation of HIF-1alpha expression in CD4(+) T cells in hypoxia gravely relies on its transcriptional upregulation and subsequent enhanced protein stabilization. PMID- 26150320 TI - Understanding filamentary growth in electrochemical metallization memory cells using kinetic Monte Carlo simulations. AB - We report on a 2D kinetic Monte Carlo model that describes the resistive switching in electrochemical metallization cells. To simulate the switching process, we consider several different processes on the atomic scale: electron transfer reactions at the boundaries, ion migration, adsorption/desorption from/to interfaces, surface diffusion and nucleation. These processes result in a growth/dissolution of a metallic filament within an insulating matrix. In addition, the model includes electron tunneling between the growing filament and the counter electrode, which allows for simulating multilevel switching. It is shown that the simulation model can reproduce the reported switching kinetics, switching variability and multilevel capabilities of ECM devices. As a major result, the influence of mechanical stress working on the host matrix due to the filamentary growth is investigated. It is demonstrated that the size and shape of the filament depend on the Young's modulus of the insulating matrix. For high values a wire-like structure evolves, whereas the shape is dendritic if the Young's modulus is negligible. PMID- 26150322 TI - Erratum. PMID- 26150321 TI - Predictors of root resorption associated with maxillary canine impaction in panoramic images. AB - OBJECTIVES: The aim was to identify a prediction model for root resorption (RR) caused by impacted canines based on radiographic variables assessed on 2D panoramic radiographs with the intention to reduce the need for additional cone beam computed tomography (CBCT) imaging. MATERIALS AND METHODS: Three hundred and six patients (188 female, 118 male; mean age, 14.7 years; standard deviation, 5.6; range, 8.4-47.2 years) were included in the study. In total, 406 impacted maxillary canines were studied, from 206 patients with unilateral impaction and from 100 patients with bilateral impaction. Initial 2D panoramic radiography was available, and 3D CBCT imaging was obtained upon clinical indication. The generated radiographic variables and specific features investigated were collected on 2D panoramic imaging and were correlated to the presence/absence of RR detected on CBCT. A validation sample consisting of 55 canines from 45 patients with maxillary canine impactions was collected to validate the outcome of the present study. RESULTS: The incidence of RR of the adjacent teeth was 33.8%. A prediction model using panoramic images for the possible presence of RR was established [area under the curve (AUC) = 0.74, 95% confidence interval (CI): 0.69-0.79] and validated by applying leave-one-out cross-validation (AUC = 0.71, 95% CI: 0.66-0.77). For the subgroup of presence of severe RR the discriminative ability increased to 0.80. In this prediction model, patient gender, canine apex, vertical canine crown position, and canine magnification were the strongest predictors for RR. CONCLUSIONS: The final prediction model for RR based on available panoramic radiographs could be a helpful tool in justifying the need of additional CBCT examination. PMID- 26150325 TI - Nursing Home Staff Palliative Care Knowledge and Practices: Results of a Large Survey of Frontline Workers. AB - CONTEXT: Deficits in quality end-of-life care for nursing home (NH) residents are well known. Palliative care is promoted as an approach to improve quality. The Palliative Care Survey (PCS) is designed to measure NH staff palliative care knowledge and practice. OBJECTIVES: To comparing palliative care knowledge and practices across NH staff roles using the PCS, and to examine relationships between facility characteristics and PCS scores. METHODS: The PCS was administered to frontline NH staff-certified nursing assistants (CNAs), licensed practical nurses (LPNs), registered nurses (RNs), and social workers (SWs)-in 51 facilities in 2012. Descriptive statistics were calculated by job role. Linear mixed effects models were used to identify facility and individual factors associated with palliative care practice and knowledge. RESULTS: The analytic sample included 1200 surveys. CNAs had significantly lower practice and knowledge scores compared to LPNs, RNs, and SWs (P < 0.05). LPNs had significantly lower psychological, end-of-life, and total knowledge scores than RNs (P < 0.05 for all). Although knowledge about physical symptoms was uniformly high, end-of-life knowledge was notably low for all staff. A one-point higher facility star rating was significantly associated with a 0.06 increase in family communication score (P = 0.003; 95% CI: 0.02-0.09; SE = 0.02). Higher penetration of hospice in the NH was associated with higher end-of-life knowledge (P = 0.003; parameter estimate = 0.006; 95% CI: 0.002-0.010; SE = 0.002). Sixty-two percent of respondents stated that, with additional training, they would be interested in being leaders in palliative care. CONCLUSION: Given observed differences in palliative care practice and knowledge scores by staff training, it appears the PCS is a useful tool to assess NH staff. Low end-of-life knowledge scores represent an important target for quality improvement. PMID- 26150326 TI - Mouse Genome Database: From sequence to phenotypes and disease models. AB - The Mouse Genome Database (MGD, www.informatics.jax.org) is the international scientific database for genetic, genomic, and biological data on the laboratory mouse to support the research requirements of the biomedical community. To accomplish this goal, MGD provides broad data coverage, serves as the authoritative standard for mouse nomenclature for genes, mutants, and strains, and curates and integrates many types of data from literature and electronic sources. Among the key data sets MGD supports are: the complete catalog of mouse genes and genome features, comparative homology data for mouse and vertebrate genes, the authoritative set of Gene Ontology (GO) annotations for mouse gene functions, a comprehensive catalog of mouse mutations and their phenotypes, and a curated compendium of mouse models of human diseases. Here, we describe the data acquisition process, specifics about MGD's key data areas, methods to access and query MGD data, and outreach and user help facilities. PMID- 26150327 TI - Explaining psychological insulin resistance in adults with non-insulin-treated type 2 diabetes: The roles of diabetes distress and current medication concerns. Results from Diabetes MILES--Australia. AB - AIMS: To investigate the contribution of general and diabetes-specific emotional wellbeing and beliefs about medicines in the prediction of insulin therapy appraisals in adults with non-insulin-treated type 2 diabetes. METHODS: The sample included Diabetes MILES-Australia cross-sectional survey participants whose primary diabetes treatment was oral hypoglycaemic agents (N=313; 49% women; mean+/-SD age: 57+/-9 years; diabetes duration: 7+/-6 years). They completed validated measures of beliefs about the 'harm' and 'overuse' of medications in general (BMQ General); 'concerns' about and 'necessity' of current diabetes medications (BMQ Specific); negative insulin therapy appraisals (ITAS); depression (PHQ-9); anxiety (GAD-7), and diabetes distress (DDS-17). Factors associated with ITAS Negative scores were examined using hierarchical multiple regressions. RESULTS: Twenty-two percent of the variance in ITAS Negative scores (52+/-10), was explained by: number of complications (beta=-.15, p=.005), DDS-17 subscale 'emotional burden' (beta=.23, p<.001), and 'concerns' about current diabetes treatment (beta=.29, p<.001). General beliefs about medications and general emotional wellbeing did not contribute significantly to the model. CONCLUSIONS: Psychological insulin resistance may reflect broader distress about diabetes and concerns about its treatment but not general beliefs about medicines, depression or anxiety. Reducing diabetes distress and current treatment concerns may improve attitudes towards insulin as a potential therapeutic option. PMID- 26150328 TI - Use of a basal-plus insulin regimen in persons with type 2 diabetes stratified by age and body mass index: A pooled analysis of four clinical trials. AB - AIMS: To evaluate the efficacy and safety of adding a single bolus dose of insulin glulisine to basal insulin ('basal-plus') in persons with type 2 diabetes. METHODS: Data from patients with poor glycemic control on oral antihyperglycemic drugs who were initiated on a 'basal-plus' regimen for up to 6 months were pooled from four randomized, multicenter studies. Glycated hemoglobin (HbA1c), fasting blood glucose, postprandial glucose (PPG), insulin dose and demographics were measured at baseline and end of study. RESULTS: 711 patients with a mean age of 59.9 years and a mean duration of diabetes of 11.0 years were included in the analysis population. A 'basal-plus' regimen was associated with significant decreases in HbA1c and PPG at 6 months, an increase in glargine and glulisine doses and small, but statistically significant, changes in body weight and BMI in all patient subsets. The proportion of patients with HbA1c<7% also increased in all populations studied, while the prevalence of severe hypoglycemia was low and did not significantly differ across patient groups. CONCLUSIONS: These results suggest that the use of 'basal-plus' can achieve a good therapeutic response with a low risk of hypoglycemia and weight gain, regardless of a patient's age or BMI. PMID- 26150329 TI - Effect of sweating set rate on clothing real evaporative resistance determined on a sweating thermal manikin in a so-called isothermal condition (T manikin = T a = T r). AB - The ASTM F2370 (2010) is the only standard with regard to measurement of clothing real evaporative resistance by means of a sweating manikin. However, the sweating set-point is not recommended in the standard. In this study, the effect of sweating rate on clothing real evaporative resistance was investigated on a 34 zone "Newton" sweating thermal manikin in a so-called isothermal condition (T manikin = T a = T r). Four different sweating set rates (i.e., all segments had a sweating rate of 400, 800, 1200 ml/hr ? m(2), respectively, and different sweating rates were assigned to different segments) were applied to determine the clothing real evaporative resistance of five clothing ensembles and the boundary air layer. The results indicated that the sweating rate did not affect the real evaporative resistance of clothing ensembles with the absence of strong moisture absorbent layers. For the clothing ensemble with tight cotton underwear, a sweating rate of lower than 400 ml/hr ? m(2) is not recommended. This is mainly because the wet fabric "skin" might not be fully saturated and thus led to a lower evaporative heat loss and thereby a higher real evaporative resistance. For vapor permeable clothing, the real evaporative resistance determined in the so called isothermal condition should be corrected before being used in thermal comfort or heat strain models. However, the reduction of wet thermal insulation due to moisture absorption in different test scenarios had a limited contribution to the effect of sweating rate on the real evaporative resistance. PMID- 26150330 TI - Magnetic Force Microscopy in Liquids. AB - In this work, the use of magnetic force microscopy (MFM) to acquire images of magnetic nanostructures in liquid environments is presented. Optimization of the MFM signal acquisition in liquid media is performed and it is applied to characterize the magnetic signal of magnetite nanoparticles. The ability for detecting magnetic nanostructures along with the well-known capabilities of atomic force microscopy in liquids suggests potential applications in fields such as nanomedicine, nanobiotechnology, or nanocatalysis. PMID- 26150331 TI - Synaptic-vesicle fusion: a need for speed. PMID- 26150332 TI - Results of deformity correction in children with X-linked hereditary hypophosphatemic rickets by external fixation or combined technique. AB - BACKGROUND: The operative procedures to correct multiplanar bone deformities may be indicated for prevention of secondary orthopaedic complications in children with X-linked hereditary hypophosphatemic rickets (XHPR). Different problems related to surgical correction were reported: increased rate of non-union, delayed union, recurrent deformity, deep intramedullary infection, refracture, nerve palsy, and pin tract infection. The aim of this retrospective study was comparison of results of correction in children with XHPR who underwent the treatment with either the Ilizarov device alone or a combined technique: the Ilizarov fixator with flexible intramedullary nailing (FIN) with hydroxyapatite bioactive coating and FIN. MATERIAL AND METHODS: We retrospectively analysed 47 cases (children of age under 14 years) affected by XHPR. Simultaneous deformity correction in femur and tibia was performed with the Ilizarov device (group I) or the combined method (group II). This article is based on the results of a historical comparative retrospective study from the same institution. RESULTS: The duration of external fixation is noted to be shorter applying the combined technique: 124.7 days (group I) vs 87.4 days (group II). In both groups deformity correction was achieved with a proper alignment. Nevertheless, while a child continues to grow during long-term follow-up, deviations of the mechanic axis from the centre of the knee joint have been developing again and values of mLDFA, mMPTA have become pathologic in the most of the cases. In group I location of a newly developed deformity resembled a pre-operative one, whereby both diaphyseal and metaphyseal parts were deformed. In group II in all the cases an apex of deformity was located in distal metadiaphyseal zone of the femur and proximal metadiaphyseal zone of the tibia. It is important to note that all of those in group II were out of the zone of the intramedullary nail. CONCLUSION: Simultaneous correction of femoral and tibial deformities by means of circular external fixators is preferable. Application of a combined osteosynthesis allows to considerably reduce the duration of external fixation and decrease the number of complications. There were no recurrent deformities in parts of bone reinforced by intramedullary nails. PMID- 26150333 TI - Haemodynamic assessment in simulated operative positions before knee arthroplasty can be useful in deep vein thrombosis prediction. AB - PURPOSE: During knee arthroplasty, the leg is placed in several forced positions, which are mainly uncomfortable for all tissue structures in the region, including the vascular structures. Veins have a weaker quality of the wall structure than arteries, so during the forced position morphological and haemodynamic consequences are expected mainly in the venous system. Conditions of safe aseptic environment for the arthroplasty are in collision with routine intra-operative analysis of local haemodynamics in real time. This is the reason why we have no insight into the haemodynamic and morphological changes at the time in which the initiation of deep vein thrombosis (DVT) occurs. For this reason we created the hypothesis that the monitoring of the occurrence and detection of potential DVT risks can be achieved pre-operatively using echosonograms in simulated operative positions, and then compare them with the cases of postoperative DVT. METHODS: This research was conducted as a prospective, analytical, minimally manipulative and observational clinical study in the period January 2011 to October 2013. In the preoperative period we made ultrasound and colour-Doppler examinations of deep veins in simulated operative position (full extension 0 degrees , semiflexion 30-60 degrees , flexion 90 degrees and maximal flexion 90 degrees +). The target vein was the posterior tibial vein in the distal third of calf. During the operation we took a note of anaesthesia duration and forced positions duration. After the operation we were looking for ultrasound signs of DVT in a follow-up period of six weeks. The sample was made from 91 patients selected for knee arthroplasty: 56 women and 35 men patients of average age 67.46 years. The oldest patient was 81, and the youngest 48. Average body mass index was 26.98 (+/ 2.20) kg/m(2). After initial ultrasound, the sample was divided into two groups according to vein flow velocity. Patients who had a flow velocity lower than 10 cm/s in any of the forced positions were in the investigated group (N-b, n = 38), and patients who had more favourable haemodynamics in forced positions were in the control group (N-a, n = 53). Patients underwent arthroplasty without tourniquet, and the operative, postoperative and anaesthesiological protocol was the same for all the patients. RESULTS: Friedman's test results point out significant differences of posterior tibial vein flow velocity in four simulated positions (0 degrees , 30-60 degrees , 90 degrees , 90 degrees +). Overview of the median value of the posterior tibial vein flow velocity points out reduction of the posterior tibial vein flow velocity in the third and fourth simulated positions. Average range values were lowest in simulated position 90 degrees +. Relative risk for the DVT occurrence was 21.6% higher in the group of patients with flow velocity lower than 10 cm/s with statistical significance. The incidence of DVT was higher in women (22.85%) than in men (14.28%). There was one (1.09%) case of pulmonary embolism (PE) presented as segmental PE. CONCLUSIONS: We believe that preoperative ultrasound analysis performed during the simulation of operative positions is a useful pre-operative test that can identify patients at risk of developing postoperative DVT. We would recommend that during surgery procedure to minimise forced position of knee flexion. PMID- 26150334 TI - Age-dependent variation of glenohumeral anatomy: a radiological study. AB - PURPOSE: Profound knowledge of variations in shoulder anatomy is gaining relevance in daily clinical work. In our study, we examine age-dependent variations of glenohumeral parameters in healthy individuals. METHODS: In this analysis, 774 severely injured patients who received a whole-body computed tomography (CT) scan were included. Patients with shoulder fractures were excluded. The resulting scans were split into two groups: patients younger than 25 (group 1) and older than 60 years (group 2). These groups were divided into four subgroups according to gender. Shoulder scans with advanced osteoarthritis were then removed. In order to maintain equal group size, redundant patients were randomly removed. RESULTS: A total of 210 measurements from 106 patients were included. The humeral head diameter (group 1: 41.6 +/- 3.7 mm, group 2: 44.5 +/- 3.7 mm, p < 0.001) and glenoid surface (group 1: 627.0 +/- 110.8 mm(2), group 2: 763.9 +/- 148.5 mm(2), p < 0.001) showed higher values in the group of older patients. Older patients also had a higher glenoid inclination (group 1: 50.9 +/- 6.9 degrees , group 2: 55.7 +/- 8.8 degrees , p < 0.001) as well as an increased glenoid to head ratio (group 1: 0.61 +/- 0.04, group 2: 0.64 +/- 0.05, p < 0.001). CONCLUSIONS: Increased sizes of humeral head and glenoid surface are present in older patients without signs of osteoarthritis. Moreover, in patients with increased age more glenoid inclination as well as an increased glenoid to head ratio was revealed. These age-dependent anatomical parameters should be considered during planning of operative procedures of the shoulder joint. PMID- 26150335 TI - Oblique femoral shortening osteotomy in total hip arthroplasty for high dislocation in patients with hip dysplasia. AB - PURPOSE: The aim of this study was to evaluate outcomes after implantation of total hip arthroplasty for developmental dysplasia with high dislocation of the hip using conical stems combined with oblique subtrochanteric shortening osteotomy. METHODS: We retrospectively reviewed the functional scores, radiographic results, and complications in a consecutive series of 16 hips (12 patients) with Crowe IV developmental dysplasia of the hip. The average age at surgery was 53.2 years and the patients were operated on between 1999 and 2008. RESULTS: The average Harris Hip Score improved from 37.2 to 83.7 at a mean follow up of 8.7 years. All acetabular cups were inserted into the true acetabulum and all prosthetic components were stable at the last follow-up visit. No neurovascular damage was recorded. Complications arose in six hips (37.5%): intra operative fracture of proximal femur requiring fixation (n = 2); dislocation (n = 3); and asymptomatic non-union of the osteotomy (n = 1). The osteotomy healed within less than six months in all the remaining cases. CONCLUSIONS: With the numbers given the oblique femur shortening osteotomy led to an increased rotational stability and proved to be a simple and effective method. Compared with transverse osteotomy and as related to our experience, this technique may be a method of choice in selected cases. PMID- 26150336 TI - Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells. AB - Glioblastoma stem cells (GSCs) are the initiating cells in glioblastoma multiforme (GBM) and contribute to the resistance of GBM to chemotherapy and radiation. In the present study, we investigated the effects of cardamonin (3,4,2,4-tetrahydroxychalcone) on the self-renewal and apoptosis of GSCs, and if its action is associated with signal transducer and activator of transcription 3 (STAT3) pathway. CD133(+) GSCs, a kind of GSCs line, was established from human glioblastoma tissues. Cardamonin inhibited the proliferation and induced apoptosis in CD133+ GSCs. The proapoptotic effects of temozolomide (TMZ) were further enhanced by cardamonin in CD133+ GSCs and U87 cells in vitro. For in vivo study, injection of 5 * 10(5) cells of CD133+ GSCs subcutaneously (s.c.) into nude mice, 100 % of large tumors were developed within 8 weeks in all mice; in contrast, only one out of five mice developed a small tumor when 5 * 10(5) cells of CD133(-) GMBs cells were injected. Cardamonin also inhibited STAT3 activation by luciferase assay and suppressed the expression of the downstream genes of STAT3, such as Bcl-XL, Bcl-2, Mcl-1, survivin, and VEGF. Furthermore, cardamonin locked nuclear translocation and dimerization of STAT3 in CD133(+) GSCs. Docking analysis confirmed that cardamonin molecule was successfully docked into the active sites of STAT3 with a highly favorable binding energy of -10.78 kcal/mol. The study provides evidence that cardamonin is a novel inhibitor of STAT3 and has the potential to be developed as a new anticancer agent targeting GSCs. This study also reveals that targeting STAT3 signal pathway is an important strategy for the treatment of human GBM. PMID- 26150337 TI - Extracellular vesicles from women with breast cancer promote an epithelial mesenchymal transition-like process in mammary epithelial cells MCF10A. AB - Extracellular vesicles (EVs) mediate many stages of tumor progression including angiogenesis, escape from immune surveillance, and extracellular matrix degradation. We studied whether EVs from plasma of women with breast cancer are able to induce an epithelial-mesenchymal transition (EMT) process in mammary epithelial cells MCF10A. Our findings demonstrate that EVs from plasma of breast cancer patients induce a downregulation of E-cadherin expression and an increase of vimentin and N-cadherin expression. Moreover, EVs induce migration and invasion, as well as an increase of NFkappaB-DNA binding activity and MMP-2 and MMP-9 secretions. In summary, our findings demonstrate, for the first time, that EVs from breast cancer patients induce an EMT-like process in human mammary non tumorigenic epithelial cells MCF10A. PMID- 26150338 TI - miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer. AB - MicroRNA-9 upregulation was reported in several tumors. However, its function and mechanism in human bladder cancer remains obscure. The present study aims to identify the expression pattern, biological roles and potential mechanism of miR 9 in human bladder cancers. We found that expression level of miR-9 in bladder cancer tissues was higher than normal tissues. miR-9 mimic transfection was performed in T24 and 5637 cells with low miR-9 expression, and miR-9 inhibitor was employed in BIU-87 cell line with high endogenous expression. miR-9 increased cell proliferation, cell cycle progression, invasion and chemoresistance, with upregulation of cyclin D1, MMP9, Bcl-2, and survivin and downregulation of E cadherin. Using luciferase reporter assay, we confirmed that LASS2 was a direct target of miR-9 in bladder cancer cells. Transfection of miR-9 mimic downregulated LASS2 expression. LASS2 transfection downregulated Bcl-2 and survivin expression, which were induced by miR-9 mimic in both cell lines. In conclusion, these results indicate that miR-9 upregulation might be associated with malignant phenotype of bladder cancer. miR-9 promotes chemoresistance of bladder cancer cells by target LASS2. PMID- 26150339 TI - Is second-line systemic chemotherapy beneficial in patients with non-small cell lung cancer (NSCLC)? A multicenter data evaluation by the Anatolian Society of Medical Oncology. AB - Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate. PMID- 26150340 TI - Histone deacetylase 6 promotes growth of glioblastoma through inhibition of SMAD2 signaling. AB - Histone deacetylases (HDACs) play a role in the tumorigenesis of glioblastoma multiforme (GBM), whereas the underlying mechanism has not been elucidated. Here, we reported significantly higher HDAC6 levels in GBM from the patients. GBM cell growth was significantly inhibited by ACY-1215, a specific HDAC6 inhibitor. Further analyses show that HDAC6 may promote growth of GBM cells through inhibition of SMAD2 phosphorylation to downregulate p21. Thus, our data demonstrate a previously unrecognized regulation pathway in that HDAC6 increases GBM growth through attenuating transforming growth factor beta (TGFbeta) receptor signaling. PMID- 26150342 TI - Laparoscopic versus open distal pancreatectomy: is a randomized trial necessary? PMID- 26150341 TI - Tau pathology spread in PS19 tau transgenic mice following locus coeruleus (LC) injections of synthetic tau fibrils is determined by the LC's afferent and efferent connections. AB - Filamentous tau inclusions are hallmarks of Alzheimer's disease (AD) and other neurodegenerative tauopathies. An increasing number of studies implicate the cell to-cell propagation of tau pathology in the progression of tauopathies. We recently showed (Iba et al., J Neurosci 33:1024-1037, 2013) that inoculation of preformed synthetic tau fibrils (tau PFFs) into the hippocampus of young transgenic (Tg) mice (PS19) overexpressing human P301S mutant tau induced robust tau pathology in anatomically connected brain regions including the locus coeruleus (LC). Since Braak and colleagues hypothesized that the LC is the first brain structure to develop tau lesions and since LC has widespread connections throughout the CNS, LC neurons could be the critical initiators of the stereotypical spreading of tau pathology through connectome-dependent transmission of pathological tau in AD. Here, we report that injections of tau PFFs into the LC of PS19 mice induced propagation of tau pathology to major afferents and efferents of the LC. Notably, tau pathology propagated along LC efferent projections was localized not only to axon terminals but also to neuronal perikarya, suggesting transneuronal transfer of templated tau pathology to neurons receiving LC projections. Further, brainstem neurons giving rise to major LC afferents also developed perikaryal tau pathology. Surprisingly, while tangle-bearing neurons degenerated in the LC ipsilateral to the injection site starting 6 months post-injection, no neuron loss was seen in the contralateral LC wherein tangle-bearing neurons gradually cleared tau pathology by 6-12 months post-injection. However, the spreading pattern of tau pathology observed in our LC-injected mice is different from that in AD brains since hippocampus and entorhinal cortex, which are affected in early stages of AD, were largely spared of tau inclusions in our model. Thus, while our study tested critical aspects of the Braak hypothesis of tau pathology spread, this novel mouse model provides unique opportunities to elucidate mechanisms underlying the selective vulnerability of neurons to acquire tau pathology and succumb to or resist tau mediated neurodegeneration. PMID- 26150343 TI - Regulatory aspects of small molecule drugs for heart regeneration. AB - Even though recent discoveries prove the existence of cardiac progenitor cells, internal regenerative capacity of the heart is minimal. As cardiovascular disease is the leading cause of deaths in the United States, a number of approaches are being used to develop treatments for heart repair and regeneration. Small molecule drugs are of particular interest as they are suited for oral administration and can be chemically synthesized. However, the regulatory process for the development of new treatment modalities is protracted, complex and expensive. One of the hurdles to development of appropriate therapies is the need for predictive preclinical models. The use of patient-derived cardiomyocytes from iPSC cells represents a novel tool for this purpose. Among other concepts for induction of heart regeneration, the most advanced is the combination of DPP-IV inhibitors with stem cell mobilizers. This review will focus on regulatory aspects as well as preclinical hurdles of development of new treatments for heart regeneration. PMID- 26150345 TI - The 4th S-ECCO IBD Masterclass, Barcelona, February 19, 2015. PMID- 26150346 TI - Rectovaginal fistula secondary to an erosive pessary. PMID- 26150344 TI - Bioengineering methods for myocardial regeneration. AB - The challenging task of heart regeneration is being pursued in three related directions: derivation of cardiomyocytes from human stem cells, in vitro engineering and maturation of cardiac tissues, and development of methods for controllable cell delivery into the heart. In this review, we focus on tissue engineering methods that recapitulate biophysical signaling found during normal heart development and maturation. We discuss the use of scaffold-bioreactor systems for engineering functional human cardiac tissues, and the methods for delivering stem cells, cardiomyocytes and engineered tissues into the heart. PMID- 26150347 TI - Drainoscopy: a doorway to the abdomen in the post-surgical patient. AB - The ability to optically visualize the abdominal cavity in the post-surgical patient can prove to be invaluable, particularly when imaging studies and exam findings can be difficult to interpret. Post-surgical drains are often used and provide a window into the abdominal cavity. In this proof-of-concept study, it is demonstrated that an ordinary drain can be used as a point of access and hence a doorway into the abdominal cavity. This technique has been termed drainoscopy, and the approach is demonstrated with video supplement. PMID- 26150348 TI - The effects of listener training on discriminative control by elements of compound stimuli in children with disabilities. AB - The purpose of the current study was to assess whether the establishment of listener relations with compound stimuli as samples and comparisons would lead to the emergence of: (1) speaker behavior in the form of tacts of the compound stimuli; (2) listener and tact responses for untaught compounds; and (3) listener and tact responses for the isolated properties of compounds. Participants were four boys diagnosed with autism and one diagnosed with intellectual disability. We taught participants to select among three compound comparisons consisting of combinations of shapes and patterns in the presence of the corresponding dictated word. Subsequently, we tested for the emergence of tacts for the trained compounds, as well as tact and listener relations for six untaught compounds and their properties. In general, results showed that the acquisition of listener relations led to the emergence of the corresponding tacts, as well as the emergence of listener and tact responses for untaught combinations for three out of five participants. By contrast, the other two participants showed responding characteristic of restricted stimulus control. These results suggest that the establishment of bidirectional relations between listener and speaker behaviors may facilitate the emergence of control by properties of compound stimuli. PMID- 26150349 TI - Revisiting conjugate schedules. AB - The effects of conjugate reinforcement on the responding of 13 college students were examined in three experiments. Conjugate reinforcement was provided via key presses that changed the clarity of pictures displayed on a computer monitor in a manner proportional to the rate of responding. Experiment 1, which included seven parameters of clarity change per response, revealed that responding decreased as the percentage clarity per response increased for all five participants. These results indicate that each participant's responding was sensitive to intensity change, which is a parameter of conjugate reinforcement schedules. Experiment 2 showed that responding increased during conjugate reinforcement phases and decreased during extinction phases for all four participants. Experiment 3 also showed that responding increased during conjugate reinforcement and further showed that responding decreased during a conjugate negative punishment condition for another four participants. Directions for future research with conjugate schedules are briefly discussed. PMID- 26150350 TI - Risk factors for, and the effect of MRSA colonization on the clinical outcomes of severely burnt patients. AB - BACKGROUND: MRSA is an on-going problem for burn patients. AIM: To analyze risk factors for, and the effect of MRSA colonization on burn patients' outcome. METHODS: During 21 months burn patients' details and MRSA isolates were analyzed, and a case-control study performed. RESULTS: Of 357 burn patients, 57 (16%) tested positive for MRSA. Compared to the MRSA negative group, MRSA positive patients had a higher median total burn surface area (15%[IQR 5-17%] vs. 5%[IQR 2 8%]; p<0.001), more admissions to ICU (54% vs. 26%; p<0.001), longer ICU length of stay (4.3 vs. 1.0 days; p<0.001), required more operations (1.6 vs. 0.8; p<0.001), and had longer total hospital length of stay (25.5 vs. 8.0 days; p<0.001). MRSA positivity was a significant independent predictor of increased length of stay (6.0 days, 95%CI 2.39-9.6 days; p=0.001) in a multivariable regression model correcting for patients TBSA and co-morbidities. Cardiac comorbidities (OR 5.14, 95%CI 1.76-15.62; p<0.001) and a longer exposure to the hospital environment (OR 1.05, 95%CI 1.02-1.09, p=0.005) increased the likelihood for MRSA positivity. CONCLUSION: The negative impact of MRSA positivity on burn patients outcome indicates the need for improved screening procedures for early identification and further efforts toward MRSA infection control to prevent cross infection as this may significantly impair patients' outcome. PMID- 26150351 TI - [Langerhans cell histiocytosis in adults]. AB - Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells, most often organized in granulomas. The disease has been initially described in children. The clinical picture of LCH is highly variable. Bone, skin, pituitary gland, lung, central nervous system, lymphoid organs are the main organs involved whereas liver and intestinal tract localizations are less frequently encountered. LCH course ranges from a fulminant multisystem disease to spontaneous resolution. Several randomized controlled trials have enable pediatricians to refine the management of children with LCH. Adult LCH has some specific features and poses distinct therapeutic challenges, knowing that data on these patients are limited. Herein, we will provide an overview of current knowledge regarding adult LCH and its management. We will also discuss recent advances in the understanding of the disease, (i.e. the role of BRAF oncogene) that opens the way toward targeted therapies. PMID- 26150352 TI - Multiply Confined Nickel Nanocatalysts Produced by Atomic Layer Deposition for Hydrogenation Reactions. AB - To design highly efficient catalysts, new concepts for optimizing the metal support interactions are desirable. Here we introduce a facile and general template approach assisted by atomic layer deposition (ALD), to fabricate a multiply confined Ni-based nanocatalyst. The Ni nanoparticles are not only confined in Al2 O3 nanotubes, but also embedded in the cavities of Al2 O3 interior wall. The cavities create more Ni-Al2 O3 interfacial sites, which facilitate hydrogenation reactions. The nanotubes inhibit the leaching and detachment of Ni nanoparticles. Compared with the Ni-based catalyst supported on the outer surface of Al2 O3 nanotubes, the multiply confined catalyst shows a striking improvement of catalytic activity and stability in hydrogenation reactions. Our ALD-assisted template method is general and can be extended for other multiply confined nanoreactors, which may have potential applications in many heterogeneous reactions. PMID- 26150353 TI - The role of Pin1 protein in aging of human tendon stem/progenitor cells. AB - Aging of tendon stem/progenitor cells (TSPCs) can lead to tissue degeneration and subsequent injury. However, the molecular mechanisms controlling TSPC aging are not completely understood. In the present study, we investigated the role of Pin1 in aging of human TSPCs. Pin1 mRNA and protein expression levels were significantly decreased during prolonged in vitro culture of human TSPCs. Furthermore, overexpression of Pin1 delayed the progression of cellular senescence, as confirmed by downregulation of senescence-associated beta galactosidase, increased telomerase activity and decreased levels of the senescence marker, p16(INK4A). Conversely, Pin1 siRNA transfection promoted senescence in TSPCs. In addition, miR-140-5p regulated Pin1 expression at the translational level via directly targeting its 3'UTR. Our results collectively demonstrate that Pin1 acts as an important regulator of TSPC aging. PMID- 26150354 TI - Effects of hypergravity on adipose-derived stem cell morphology, mechanical property and proliferation. AB - Alteration in specific inertial conditions can lead to changes in morphology, proliferation, mechanical properties and cytoskeleton of cells. In this report, the effects of hypergravity on morphology of Adipose-Derived Stem Cells (ADSCs) are indicated. ADSCs were repeatedly exposed to discontinuous hypergravity conditions of 10 g, 20 g, 40 g and 60 g by utilizing centrifuge (three times of 20 min exposure, with an interval of 40 min at 1 g). Cell morphology in terms of length, width and cell elongation index and cytoskeleton of actin filaments and microtubules were analyzed by image processing. Consistent changes observed in cell elongation index as morphological change. Moreover, cell proliferation was assessed and mechanical properties of cells in case of elastic modulus of cells were evaluated by Atomic Force Microscopy. Increase in proliferation and decrease in elastic modulus of cells are further results of this study. Staining ADSC was done to show changes in cytoskeleton of the cells associated to hypergravity condition specifically in microfilament and microtubule components. After exposing to hypergravity, significant changes were observed in microfilaments and microtubule density as components of cytoskeleton. It was concluded that there could be a relationship between changes in morphology and MFs as the main component of the cells. PMID- 26150356 TI - A Step-by-Step Assembly of a 3D Coordination Polymer in the Solid-State by Desolvation and [2+2] Cycloaddition Reactions. AB - Two solid-state structural transformations that occur in a stepwise and a controlled manner are described. A combination of desolvation and cycloaddition reactions has been employed to synthesise a 3D coordination polymer (CP) from 1D CP [Cd(bdc)(4-spy)2 (H2 O)]?2 H2 O?2 DMF (bdc=1,4-benzenedicarboxylate, 4-spy=4 styrylpyridine) presumably via a 2D layered structure, [Cd2 (bdc)2 (4-spy)4 ]. In the absence of single crystals to follow the course of the photocycloaddition reaction, thermogravimetry, XAFS and NOESY NMR experiments were used to propose the formation of layered and pillared layered structures. Further, the present strategy enables us to synthesise new multidimensional architectures that are otherwise inaccessible by the self-assembly process. PMID- 26150357 TI - Phase transition characteristics and associated piezoelectricity of potassium sodium niobate lead-free ceramics. AB - To achieve high piezoelectric activity and a wide sintering temperature range, the ceramic system concerning (1 - x)(K(0.48)Na(0.52))(Nb(0.96)Sb(0.04))O(3) x[Bi(0.5)(Na(0.7)Ag(0.3))(0.5)](0.90) Zn(0.10)ZrO(3) was designed, and the rhombohedral-tetragonal (R-T) phase boundary can drive a high d(33). Phase transition characteristics as well as their effects on the electrical properties were investigated systematically. The R-T coexistence phase boundary (0.04 <= x <= 0.05) can be driven via modification with BNAZZ, and has been confirmed by XRD and temperature-dependent dielectric constants as well as Raman analysis, and the ceramics possess enhanced piezoelectric properties (d(33) ~ 425 pC N(-1) and k(p) ~ 0.43) and a high unipolar strain (~0.3%). In addition, a wide sintering temperature range of 1050-1080 degrees C can warrant a large d(33) of 400-430 pC N(-1), which can benefit practical applications. As a result, the addition of BNAZZ is an effective method to improve the electrical properties (piezoelectricity and strain) and sintering behavior of potassium-sodium niobate ceramics. PMID- 26150355 TI - LMAN1 (ERGIC-53) is a potential carrier protein for matrix metalloproteinase-9 glycoprotein secretion. AB - Matrix metalloproteinase-9 (MMP-9) is a secreted glycoprotein with a major role in shaping the extracellular matrix and a detailed understanding of the secretory mechanism could help identify methods to correct diseases resulting from dysregulation of secretion. MMP-9 appears to follow a canonical secretory pathway through a quality control cycle in the endoplasmic reticulum (ER) before transport of the properly folded protein to the Golgi apparatus and beyond for secretion. Through a complementation assay, we determined that LMAN1, a well studied lectin-carrier protein, interacts with a secretion-competent N glycosylated MMP-9 in the ER while N-glycosylation-deficient secretion compromised MMP-9 does not. In contrast, co-immunoprecipitation demonstrated protein interaction between LMAN1 and secretion-compromised N-glycosylation deficient MMP-9. MMP-9 secretion was reduced in the LMAN1 knockout cell line compared to control cells confirming the functional role of LMAN1. These observations support the role of LMAN1 as a lectin-carrier protein mediating efficient MMP-9 secretion. PMID- 26150358 TI - Symptoms of prenatal depression are associated with raised salivary alpha-amylase levels. AB - PURPOSE: Prenatal depression increases risk for a number of adverse offspring outcomes, however the biological mechanisms underlying this association remain unclear. It has been suggested that maternal glucocorticoids may mediate this link, though supporting evidence has been mixed. An alternative mechanism of effect may be via depression-induced changes in maternal sympathetic nervous system (SNS) function. We examined this hypothesis by determining the relationship between symptoms of maternal prenatal depression and diurnal salivary alpha-amylase (sAA) levels. METHODS: 76 pregnant women were recruited during either the second or third trimester of pregnancy. Participants self reported depressive symptoms using the Edinburgh postnatal depression scale. Saliva samples, to be assayed for alpha-amylase activity, were collected at home over two working days. RESULTS: Participants with depressive symptoms in later pregnancy had elevated awakening sAA levels compared with non-depressed controls (t(73) = -2.737, p = 0.008), and continued to have raised sAA throughout the day (F(1) = 10.924, p = 0.002). CONCLUSIONS: Our findings highlight that symptoms of depression during late pregnancy are associated with increased maternal SNS activity. Thus, changes in maternal SNS function, which may include increased vasoconstriction and reduced foetal blood flow, could, in part, mediate associations between prenatal depression and adverse offspring outcomes. PMID- 26150360 TI - [Is smoking a chronic disease? Yes]. PMID- 26150359 TI - Anesthesia with sevoflurane in neonatal rats: Developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(-) importer antagonists. AB - BACKGROUND: 1.5 million children under 12 months of age are exposed to general anesthesia annually in the United States alone. Human and especially animal studies provide evidence that exposure to general anesthesia during the early postnatal period may lead to long-term neurocognitive abnormalities via poorly understood mechanisms. We investigated whether an immature stress response system and gamma-aminobutyric acid (GABA) type A receptor activities are involved in mediating these abnormalities. METHODS: Sprague-Dawley rats at postnatal days 4, 5 or 6 were anesthetized with 2.1% sevoflurane for 6h; maternally separated and house reared rats served as controls. RESULTS: Sevoflurane anesthesia markedly increased corticosterone levels in rat pups of both genders. In adulthood, these rats responded to stress with heightened secretion of corticosterone and a greater increase in corticosterone levels in males versus females. Only male rats, previously exposed to neonatal sevoflurane, had a higher frequency of miniature inhibitory postsynaptic currents in CA1 neurons, spent a shorter time in open arms of the elevated plus maze (EPM) and exhibited impaired prepulse inhibition (PPI) of startle. Pretreatment of male rats prior to sevoflurane with the Na(+)-K(+)-2Cl(-) cotransporter inhibitor, bumetanide, or the mineralocorticoid receptor antagonist, RU28318, normalized endocrine responses to stress and the EPM behavior in adulthood, while only those pretreated with bumetanide exhibited normalized PPI of startle responses. Neither bumetanide nor RU28318 altered the effect of sevoflurane on synaptic activity. CONCLUSIONS: Sevoflurane-enhanced neuronal excitation and elevated corticosteroid levels at the time of anesthesia contribute to the mechanisms initiating neonatal sevoflurane-induced long-term endocrine and neurobehavioral abnormalities. PMID- 26150361 TI - Role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived prostaglandin E2 in colon carcinogenesis. AB - Nonsteroidal anti-inflammatory drugs, especially selective cyclooxygenase-2 (COX 2) inhibitors, are among the most promising chemopreventive agents for colorectal cancer. However, recent clinical trials have indicated that these inhibitors pose a significantly increased cardiovascular risk. Microsomal prostaglandin E (PGE) synthase-1 (mPGES-1) and mPGES-1-derived PGE2 have gained attention recently as alternative targets to COX-2 for colorectal cancer chemoprevention and chemotherapy. In this review, we summarize the current understanding of the roles of mPGES-1, a PGE2-inactivating enzyme (15-hydroxyprostagladin dehydrogenase), and PGE2 specific receptors (EPs) in colon carcinogenesis. PMID- 26150362 TI - Strengthening community resilience efforts in disasters: Exploring the roles of public libraries. PMID- 26150363 TI - Disaster response and people experiencing homelessness: Addressing challenges of a population with limited resources. AB - In this article the authors provide an overview of some issues that inhibit disaster planning and response for people experiencing homelessness and discuss the planning process conducted for this population in Worcester, MA. People experiencing homelessness face numerous challenges in preparing for disasters both natural and human caused. Similarly, providers attempting to aid these individuals must recognize and overcome various factors that hamper efforts to provide assistance. People experiencing homelessness lack the general resources many in the United States take for granted, including food, shelter, communication methods, and transportation. The population also has an increased prevalence of medical and psychiatric conditions. These factors amplify the typical difficulties in preparedness, communication, sheltering, and training for disasters. With these principles in mind, the authors reviewed the literature for best practices, identified potential stakeholders, and developed an annex to help address organization and delivery of care to those experiencing homelessness during a disaster. PMID- 26150364 TI - Mitigating active shooter impact: Analysis for policy options based on agent/computer-based modeling. AB - Active shooting violence at confined settings, such as educational institutions, poses serious security concerns to public safety. In studying the effects of active shooter scenarios, the common denominator associated with all events, regardless of reason/intent for shooter motives, or type of weapons used, was the location chosen and time expended between the beginning of the event and its culmination. This in turn directly correlates to number of casualties incurred in any given event. The longer the event protracts, the more casualties are incurred until law enforcement or another barrier can react and culminate the situation. OBJECTIVE: Using AnyLogic technology, devise modeling scenarios to test multiple hypotheses against free-agent modeling simulation to determine the best method to reduce casualties associated with active shooter scenarios. DESIGN, SETTING, SUBJECTS: Test four possible scenarios of responding to active shooter in a public school setting using agent-based computer modeling techniques-scenario 1: basic scenario where no access control or any type of security is used within the school; scenario 2, scenario assumes that concealed carry individual(s) (5-10 percent of the work force) are present in the school; scenario 3, scenario assumes that the school has assigned resource officer; scenario 4, scenario assumes that the school has assigned resource officer and concealed carry individual(s) (5-10 percent) present in the school. MAIN OUTCOMES MEASURED: Statistical data from modeling scenarios indicating which tested hypothesis resulted in fewer casualties and quicker culmination of event. RESULTS: The use of AnyLogic proved the initial hypothesis that a decrease on response time to an active shooter scenario directly reduced victim casualties. CONCLUSIONS: Modeling tests show statistically significant fewer casualties in scenarios where on scene armed responders such as resource officers and concealed carry personnel were present. PMID- 26150365 TI - Do social media have a place in public health emergency response? AB - OBJECTIVES: To ascertain whether analyses of social media trends for various Twitter responses following a major disaster produce implications for improving the focus on public health resources and messaging to disaster victims. METHODS: Radian6 and trend analyses were used to analyze 12-hour counts of Twitter data before, during, and after the March 2011 Japanese earthquake and tsunami. Radian6 was used to organize tweets into categories of preparedness, emergency response, and public health. RESULTS: Radian6 revealed that 49 percent of tweets were either positive or somewhat positive in sentiment about preparedness and only 7 percent were negative or somewhat negative. Trend analyses revealed a rapid onset of tweet activity associated with all keywords followed by mostly fast exponential decline. Analyses indicate that opportunities for improving public health awareness by leveraging social media communications exist for as much as 5 days after a disaster. CONCLUSIONS: Analyses suggest key times for public health social media communication to promote emergency response. PMID- 26150366 TI - Conceptual framework and quantification of population vulnerability for effective emergency response planning. AB - OBJECTIVE: The study focused on the methodological advancement and analytical approach of using multilevel data to define population vulnerability and risk in bioemergency disaster planning. METHODS: The authors considered two types of vulnerabilities, transportation vulnerability that stems from lack of access to transportation (public or private) and communication vulnerability that stems from unavailability of needed language-specific communication resources. The authors used Transit Authority general transit feed data and the American Community Survey 5-year estimate data (2006-2010 summary files) to quantify these vulnerabilities. These data were integrated with Topologically Integrated Geographic Encoding and Referencing (TIGER) data for spatial analysis. A response plan was generated for Tarrant County, TX, and deemed feasible before consideration of vulnerable populations. RESULTS: The results point to the importance of integrating geographical and population demographic features that represent potential barriers to the optimum distribution and utilization of resources into the analysis of response plans. An examination of transportation vulnerabilities indicate that, of those vulnerable in Tarrant County, nearly 23,000 individuals will be at-risk of not being able to reach the Point Of Dispensing (POD) to obtain services as they are beyond walking distance to the POD and lack access to transportation resources. The analysis of language vulnerability depicts an uneven distribution resulting in nonuniform demand at PODs for translation resources. There are more than 11,000 at-risk households in the South East region of Tarrant County alone that are truly in need of translation services. CONCLUSIONS: The authors demonstrated that multiple vulnerabilities at each POD can be quantified by aggregating the vulnerability at the available granularity (ie, all blocks or block groups) in a given service area. The quantification of vulnerability at each service area facilitates a POD based at-risk analysis for the response plan. Disparities stemming from social, behavioral, cultural, economic, and health characteristics of diverse subpopulations could induce the need for additional targeted resources to support emergency response efforts. PMID- 26150367 TI - Meaning reconstruction in the face of terror: An examination of recovery and posttraumatic growth among victims of the 9/11 World Trade Center attacks. AB - This study examines the relationship between meaning reconstruction with posttraumatic growth and depreciation in the aftermath of terrorist trauma and loss. A group of individuals (n=118) who were personally affected by the September 11, 2001 terrorist attacks were surveyed about their experiences and administered the Posttraumatic Growth Inventory and Impact of Event scales. Subjects were volunteer docents at the Tribute World Trade Center Visitor Center. Results revealed that ability to make sense of one's 9/11 experience was related to recovery but not to posttraumatic growth, whereas ability to find some benefit in the experience was related to growth. In addition, location in downtown Manhattan on September 11, 2001 was related to higher levels of posttraumatic depreciation. Findings suggest that two aspects of meaning reconstruction are differentially related to recovery and posttraumatic growth. PMID- 26150368 TI - Crisis behavior: An exploration of theories in concert. AB - OBJECTIVE: How might prominent existing communication theory better explain behavior in a crisis context, when considered in concert with one another? DESIGN: This theoretical work highlights the insight to be gained using Situational Crisis Communication Theory and Bandura's notions of self-efficacy to heighten the explanatory power of the Theory of Planned Behavior as applied to communication during times of crisis. CONCLUSION: Situational Crisis Communication Theory better explains how past experience with crisis influences the attitudes and social norms of crisis behavior, while Bandura's notion of self efficacy speaks more directly to the availability of resources as contributing factors to perceived behavioral control in a crisis situation. As such, the incorporation of these well-developed notions into the broader framework of the Theory of Planned Behavior affords greater understanding of the relationship between communication and behavior during a crisis. Further exploration of this theoretical relationship is warranted. PMID- 26150369 TI - Redesigning healthcare systems to meet the health challenges associated with climate change in the twenty-first century. AB - In the twenty-first century, climate change is emerging as a significant threat to the health and well-being of the public through links to the following: extreme weather events, sea level rise, temperature-related illnesses, air pollution patterns, water security, food security, vector-borne infectious diseases, and mental health effects (as a result of extreme weather events and climate change-induced population displacement). This article discusses how national healthcare systems can be redesigned through changes in its components such as human resources, facilities and technology, health information system, and health policy to meet these challenges. PMID- 26150370 TI - The Department of Defense and Homeland Security relationship: Hurricane Katrina through Hurricane Irene. AB - This research explored federal intervention with the particular emphasis on examining how a collaborative relationship between Department of Defense (DOD) and Homeland Security (DHS) led to greater effectiveness between these two federal departments and their subordinates (United States Northern Command and Federal Emergency Management Agency, respectively) during the preparation and response phases of the disaster cycle regarding US continental-based hurricanes. Through the application of a two-phased, sequential mixed methods approach, this study determined how their relationship has led to longitudinal improvements in the years following Hurricane Katrina, focusing on hurricanes as the primary unit of analysis. PMID- 26150371 TI - Hierarchical Cu2O/CuO/Co3O4 core-shell nanowires: synthesis and electrochemical properties. AB - We prepared hierarchical Cu2O/CuO/Co3O4 core-shell nanowires (NWs) via a facile chemical deposition method followed by calcination for use as the electrode of supercapacitors. The Cu2O/CuO/Co3O4 electrode showed a specific capacitance of 318 F g(-1) at a current density of 0.5 A g(-1). 80% of the original specific capacitance was retained after 3000 cycles at a current density of 5 A g(-1). An asymmetric supercapacitor cell using Cu2O/CuO/Co3O4 NWs as the positive electrode and activated graphene as the negative electrode exhibited a maximum energy density of 12 Wh kg(-1). The electrochemical properties of the electrode were strongly related to the hierarchical nanostructure, which not only provided rich active sites but also shortened ion transport pathways. PMID- 26150372 TI - Inactivation of Geobacillus stearothermophilus spores by alkaline hydrolysis applied to medical waste treatment. AB - Although alkaline hydrolysis treatment emerges as an alternative disinfection/sterilization method for medical waste, information on its effects on the inactivation of biological indicators is scarce. The effects of alkaline treatment on the resistance of Geobacillus stearothermophilus spores were investigated and the influence of temperature (80 degrees C, 100 degrees C and 110 degrees C) and NaOH concentration was evaluated. In addition, spore inactivation in the presence of animal tissues and discarded medical components, used as surrogate of medical waste, was also assessed. The effectiveness of the alkaline treatment was carried out by determination of survival curves and D values. No significant differences were seen in D-values obtained at 80 degrees C and 100 degrees C for NaOH concentrations of 0.5 M and 0.75 M. The D-values obtained at 110 degrees C (2.3-0.5 min) were approximately 3 times lower than those at 100 degrees C (8.8-1.6 min). Independent of the presence of animal tissues and discarded medical components, 6 log10 reduction times varied between 66 and 5 min at 100 degrees C-0.1 M NaOH and 110 degrees C-1 M NaOH, respectively. The alkaline treatment may be used in future as a disinfection or sterilization alternative method for contaminated waste. PMID- 26150373 TI - Application of fly ash as an adsorbent for Estradiol in animal waste. AB - The contamination of agricultural ground with estrogen compounds through application of animal wastes is a present concern. At the same time, current uses for waste fly ash having high carbon content are limited. To help mitigate these problems, we examine using waste fly ash as a useful adsorbent for Estradiol in pig waste digests. In this study, Estradiol was added to vials containing water and fly ash from several different power plants. After an extraction process, the amount of Estradiol in the water was measured. Commercial activated carbon was also used for comparison purposes. Vials containing varying concentrations of Estradiol and no trapping material were used as a control. The results from this study indicate that fly ash can be used as a trapping material for Estradiol in water, but that commercially available activated carbon can trap about an order of magnitude more Estradiol than the fly ash and that the effects of the fly ash matrix can both inhibit and promote the solvation of Estradiol into water depending possibly upon pH and cation concentration effects. In addition, preliminary extraction studies using pig waste digest indicate that fly ash can be used as adsorbent for Estradiol present in pig waste. PMID- 26150374 TI - Use of simulation in acute neurology training: Point and counterpoint. PMID- 26150375 TI - The Impact of Colleague Peer Review on the Radiotherapy Treatment Planning Process in the Radical Treatment of Lung Cancer. AB - AIMS: Modern radiotherapy uses techniques to reliably identify tumour and reduce target volume margins. However, this can potentially lead to an increased risk of geographic miss. One source of error is the accuracy of target volume delineation (TVD). Colleague peer review (CPR) of all curative-intent lung cancer plans has been mandatory in our institution since May 2013. At least two clinical oncologists review plans, checking treatment paradigm, TVD, prescription dose tumour and critical organ tolerances. We report the impact of CPR in our institution. MATERIALS AND METHODS: Radiotherapy treatment plans of all patients receiving radical radiotherapy were presented at weekly CPR meetings after their target volumes were reviewed and signed off by the treating consultant. All cases and any resultant change to TVD (including organs at risk) or treatment intent were recorded in our prospective CPR database. The impact of CPR over a 13 month period from May 2013 to June 2014 is reported. RESULTS: One hundred and twenty two patients (63% non-small cell lung carcinoma, 17% small cell lung carcinoma and 20% 'clinical diagnosis') were analysed. On average, 3.2 cases were discussed per meeting (range 1-8). CPR resulted in a change in treatment paradigm in 3% (one patient proceeded to induction chemotherapy, two patients had high-dose palliative radiotherapy). Twenty-one (17%) had a change in TVD and one (1%) patient had a change in dose prescription. In total, 6% of patients had plan adjustment after review of dose volume histogram. CONCLUSION: The introduction of CPR in our centre has resulted in a change in a component of the treatment plan for 27% of patients receiving curative-intent lung radiotherapy. We recommend CPR as a mandatory quality assurance step in the planning process of all radical lung plans. PMID- 26150376 TI - Susceptibility cancellation of a microcoil wound with a paramagnetic-liquid filled copper capillary. AB - Even though microcoils improve the sensitivity of NMR measurement of tiny samples, magnetic-field inhomogeneity due to the bulk susceptibility effect of the coil material can cause serious resonance-line broadening. Here, we propose to fabricate the microcoil using a thin, hollow copper capillary instead of a wire and fill paramagnetic liquid inside the capillary, so as to cancel the diamagnetic contribution of the copper. Susceptibility cancellation is demonstrated using aqueous solution of NiSO4. In addition, the paramagnetic liquid serves as coolant when it is circulated through the copper capillary, effectively transferring the heat generated by radiofrequency pulses. PMID- 26150377 TI - Double and zero quantum filtered (2)H NMR analysis of D2O in intervertebral disc tissue. AB - The analysis of double and zero quantum filtered (2)H NMR spectra obtained from D2O perfused in the nucleus pulposus of human intervertebral disc tissue samples is reported. Fitting the spectra with a three-site model allows for residual quadrupolar couplings and T2 relaxation times to be measured. The analysis reveals changes in both the couplings and relaxation times as the tissue begins to show signs of degradation. The full analysis demonstrates that information about tissue hydration, water collagen interactions, and sample heterogeneity can be obtained and used to better understand the biochemical differences between healthy and degraded tissue. PMID- 26150378 TI - Accurate DOSY measure for out-of-equilibrium systems using permutated DOSY (p DOSY). AB - NMR spectroscopy is a excellent tool for monitoring in-situ chemical reactions. In particular, DOSY measurement is well suited to characterize transient species by the determination of their sizes. However, here we bring to light a difficulty in the DOSY experiments performed in out-of-equilibrium systems. On such a system, the evolution of the concentration of species interferes with the measurement process, and creates a bias on the diffusion coefficient determination that may lead to erroneous interpretations. We show that a random permutation of the series of gradient strengths used during the DOSY experiment allows to average out this bias. This approach, that we name p-DOSY does not require changes in the pulse sequences nor in the processing software, and restores completely the full accuracy of the measure. This technique is demonstrated on the monitoring of the anomerization reaction of alpha- to beta glucose. PMID- 26150379 TI - Three-Dimensional Printed Prosthesis for Repair of Superior Canal Dehiscence. AB - Outcomes following repair of superior canal dehiscence (SCD) are variable, and surgery carries a risk of persistent or recurrent SCD symptoms, as well as a risk of hearing loss and vestibulopathy. Poor outcomes may occur from inadequate repair of the SCD or mechanical insult to the membranous labyrinth. Repair of SCD using a customized, fixed-length prosthesis may address current operative limitations and improve surgical outcomes. We aim to 3-dimensionally print customized prostheses to resurface or occlude bony SCD defects. Dehiscences were created along the arcuate eminence of superior semicircular canals in cadaveric temporal bones. Prostheses were designed and created using computed tomography and a 3-dimensional printer. The prostheses occupied the superior semicircular canal defect, reflected in postrepair computed tomography scans. This novel approach to SCD repair could have advantages over current techniques. Refinement of prosthesis design and materials will be important if this approach is translated into clinical use. PMID- 26150380 TI - Relapse after localized rhabdomyosarcoma: Evaluation of the efficacy of second line chemotherapy. AB - PURPOSE: About one-third of patients with rhabdomyosarcoma relapse despite appropriate treatment and experience a poor outcome. Little meaningful improvement in the outcome of this disease has been observed over the last 30 years. There is no clear international recommendation concerning the use of salvage chemotherapy at relapse. A retrospective multicenter analysis was therefore conducted to analyze the efficacy of various second-line chemotherapy regimens in this setting. METHODS: Forty-nine patients under the age of 18, with initially localized rhabdomyosarcoma, who relapsed after first complete remission, treated in three SFCE centers (Societe Francaise des Cancers de l'Enfant) between 1995 and 2013, were analyzed. RESULTS: First relapse occurred after a median interval of 22 months and remained localized in 71.4% of cases. All patients received second-line chemotherapy with an overall response to this salvage therapy of 39.1%. Best specific response rates were 73.3 and 42.9% for carboplatin/epirubicin/vincristine-ifosfamide/vincristine/etoposide (CEV/IVE) (15 patients) and vincristine/irinotecan +/- temozolomide (VI[T]) (seven patients), respectively. Overall, 40 patients (81.6%) were then eligible for delayed local treatment (surgery and/or radiotherapy) and 30 of them (61.2%) achieved second complete remission. After a median follow-up of 5.4 years since the diagnosis of first relapse, 5-year overall survival is 49.4% (95% CI: 34.2-64.6). CONCLUSION: Salvage chemotherapy plays a central role in the management of patients with relapsed rhabdomyosarcoma. CEV/IVE and VI(T) regimens can be recommended as neoadjuvant chemotherapy before local treatment for patients with relapsed rhabdomyosarcoma. PMID- 26150381 TI - Characterization and In Vitro Evaluation of Cytotoxicity, Antimicrobial and Antioxidant Activities of Chitosans Extracted from Three Different Marine Sources. AB - Chitins in the alpha and beta isomorphs were extracted from three Tunisian marine sources shrimp (Penaeus kerathurus) waste, crab (Carcinus mediterraneus) shells and cuttlefish (Sepia officinalis) bones. The obtained chitins were transformed into chitosans, the acid-soluble form of chitin. Chitosans were characterized and their biological activities were compared. Chitosan samples were then characterized by Fourier transform infrared spectroscopy (FTIR). The results showed that all chitosans presented identical spectra. Antimicrobial, antioxidant, and antitumor activities of the extracted chitosans were investigated. In fact, cuttlefish chitosan showed the highest DPPH radical scavenging activity (83 %, 5 mg/ml), whereas it was 79 % and 76 % for shrimp and crab chitosans, respectively. However, in linoleate-beta-carotene system, cuttlefish and crab chitosans exerted higher antioxidant activity (82 % and 70 %, respectively), than shrimp chitosan (49 %). Chitosans were tested for their antimicrobial activities against three Gram-negative and four Gram-positive bacteria and five fungi. Chitosans markedly inhibited growth of most bacteria and fungi tested, although the antimicrobial activity depends on the type of microorganism and on the source of chitin. In addition, chitosans showed high antitumor activity which seemed to be dependent on the chitosan characteristics such as acetylation degree and especially the molecular weight. PMID- 26150382 TI - IL17a and IL21 combined with surgical status predict the outcome of ovarian cancer patients. AB - Aside from tumor cells, ovarian cancer-related ascites contains the immune components. The aim of this study was to evaluate whether a combination of clinical and immunological parameters can predict survival in patients with ovarian cancer. Ascites specimens and medical records from 144 ovarian cancer patients at our hospital were used as the derivation group to select target clinical and immunological factors to generate a risk-scoring system to predict patient survival. Eighty-two cases from another hospital were used as the validation group to evaluate this system. The surgical status and expression levels of interleukin 17a (IL17a) and IL21 in ascites were selected for the risk scoring system in the derivation group. The areas under the receiver operating characteristic (AUROC) curves of the overall score for disease-free survival (DFS) of the ovarian cancer patients were 0.84 in the derivation group, 0.85 in the validation group, and 0.84 for all the patients. The AUROC curves of the overall score for overall survival (OS) of cases were 0.78 in the derivation group, 0.76 in the validation group, and 0.76 for all the studied patients. Good correlations between overall risk score and survival of the ovarian cancer patients were demonstrated by sub-grouping all participants into four groups (P for trend <0.001 for DFS and OS). Therefore, acombination of clinical and immunological parameters can provide a practical scoring system to predict the survival of patients with ovarian carcinoma. IL17a and IL21 can potentially be used as prognostic and therapeutic biomarkers. PMID- 26150383 TI - Self-Stacked Reduced Graphene Oxide Nanosheets Coated with Cobalt-Nickel Hydroxide by One-Step Electrochemical Deposition toward Flexible Electrochromic Supercapacitors. AB - The implementation of an optical function into supercapacitors is an innovative approach to make energy storage devices smarter and to meet the requirements of smart electronics. Here, it is reported for the first time that nickel-cobalt hydroxide on reduced graphene oxide can be utilized for flexible electrochromic supercapacitors. A new and straightforward one-step electrochemical deposition process is introduced that is capable of simultaneously reducing GO and depositing amorphous Co(1-x)Ni(x)(OH)2 on the rGO. It is shown that the rGO nanosheets are homogeneously coated with metal hydroxide and are vertically stacked. No high temperature processes are used so that flexible polymer-based substrates can be coated. The synthesized self-stacked rGO-Co(1-x)Ni(x)(OH)2 nanosheet material exhibits pseudocapacitive charge storage behavior with excellent rate capability, high Columbic efficiency, and nondiffusion limited behavior. It is shown that the electrochemical behavior of the Ni(OH)2 can be modulated, by simultaneously depositing nickel and cobalt hydroxide, into broad oxidization and reduction bands. Further, the material exhibits electrochromic property and can switch between a bleached and transparent state. Literature comparison reveals that the performance characteristics of the rGO-Co(1 x)Ni(x)(OH)2 nanosheet material, in terms of gravimetric capacitance, areal capacitance, and long-term cycling stability, are among the highest reported values of supercapacitors with electrochromic property. PMID- 26150384 TI - Microvessel permeability correlates with diabetic peripheral neuropathy in early stage of streptozotocin-induced diabetes rats. AB - AIMS: This study aims to explore the alterations in microvessel permeability in the sciatic nerve and whether they are associated with the development of diabetic peripheral neuropathy (DPN) during the early stage of diabetes in rats. METHODS: Sprague-Dawley rats were injected with streptozotocin and assessed at 0, 2, 4, and 8 weeks. Rats in the control group received the vehicle. Changes in sciatic nerve pathology, nerve conductive velocity (NCV), permeability of microvessel, and levels of vascular endothelial growth factor (VEGF) were examined. RESULTS: The morphology and NCV of sciatic nerves showed signs of abnormality as early as 2 weeks after streptozotocin injection. The microvessel permeability as monitored by water and Evans blue content of sciatic nerve had increased dramatically at 4 and 8 weeks. The water and Evans blue content both negatively correlated with NCV. VEGF was found in axons as well as the myelin sheaths in diabetic rats but not in control rats. CONCLUSIONS: The permeability of sciatic nerves was associated with the development of DPN in the early stage of diabetes in rats. Increased expression of VEGF may have a crucial role in changes in microvessel permeability and DPN. PMID- 26150385 TI - Sally Horne-Badovinac: Taking a spin around morphogenesis. PMID- 26150386 TI - From cell biology to the microbiome: An intentional infinite loop. AB - Cell biology is the study of the structure and function of the unit or units of living organisms. Enabled by current and evolving technologies, cell biologists today are embracing new scientific challenges that span many disciplines. The eclectic nature of cell biology is core to its future and remains its enduring legacy. PMID- 26150387 TI - Myelinophagy: Schwann cells dine in. AB - When nerve injury occurs, the axon and myelin fragments distal to the injury site have to be cleared away before repair. In this issue, Gomez-Sanchez et al. (2015; J. Cell Biol. http://dx.doi.org/10.1083/jcb.201503019) find that clearance of the damaged myelin within Schwann cells occurs not by phagocytosis but rather via selective autophagy, in a process they term "myelinophagy." PMID- 26150388 TI - Control of the pericentrosomal H2O2 level by peroxiredoxin I is critical for mitotic progression. AB - Proteins associated with the centrosome play key roles in mitotic progression in mammalian cells. The activity of Cdk1-opposing phosphatases at the centrosome must be inhibited during early mitosis to prevent premature dephosphorylation of Cdh1-an activator of the ubiquitin ligase anaphase-promoting complex/cyclosome and the consequent premature degradation of mitotic activators. In this paper, we show that reversible oxidative inactivation of centrosome-bound protein phosphatases such as Cdc14B by H2O2 is likely responsible for this inhibition. The intracellular concentration of H2O2 increases as the cell cycle progresses. Whereas the centrosome is shielded from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (PrxI) during interphase, the centrosome associated PrxI is selectively inactivated through phosphorylation by Cdk1 during early mitosis, thereby exposing the centrosome to H2O2 and facilitating inactivation of centrosome-bound phosphatases. Dephosphorylation of PrxI by okadaic acid-sensitive phosphatases during late mitosis again shields the centrosome from H2O2 and thereby allows the reactivation of Cdk1-opposing phosphatases at the organelle. PMID- 26150389 TI - p53 protects against genome instability following centriole duplication failure. AB - Centriole function has been difficult to study because of a lack of specific tools that allow persistent and reversible centriole depletion. Here we combined gene targeting with an auxin-inducible degradation system to achieve rapid, titratable, and reversible control of Polo-like kinase 4 (Plk4), a master regulator of centriole biogenesis. Depletion of Plk4 led to a failure of centriole duplication that produced an irreversible cell cycle arrest within a few divisions. This arrest was not a result of a prolonged mitosis, chromosome segregation errors, or cytokinesis failure. Depleting p53 allowed cells that fail centriole duplication to proliferate indefinitely. Washout of auxin and restoration of endogenous Plk4 levels in cells that lack centrioles led to the penetrant formation of de novo centrioles that gained the ability to organize microtubules and duplicate. In summary, we uncover a p53-dependent surveillance mechanism that protects against genome instability by preventing cell growth after centriole duplication failure. PMID- 26150390 TI - Interphase centrosome organization by the PLP-Cnn scaffold is required for centrosome function. AB - Pericentriolar material (PCM) mediates the microtubule (MT) nucleation and anchoring activity of centrosomes. A scaffold organized by Centrosomin (Cnn) serves to ensure proper PCM architecture and functional changes in centrosome activity with each cell cycle. Here, we investigate the mechanisms that spatially restrict and temporally coordinate centrosome scaffold formation. Focusing on the mitotic-to-interphase transition in Drosophila melanogaster embryos, we show that the elaboration of the interphase Cnn scaffold defines a major structural rearrangement of the centrosome. We identify an unprecedented role for Pericentrin-like protein (PLP), which localizes to the tips of extended Cnn flares, to maintain robust interphase centrosome activity and promote the formation of interphase MT asters required for normal nuclear spacing, centrosome segregation, and compartmentalization of the syncytial embryo. Our data reveal that Cnn and PLP directly interact at two defined sites to coordinate the cell cycle-dependent rearrangement and scaffolding activity of the centrosome to permit normal centrosome organization, cell division, and embryonic viability. PMID- 26150391 TI - The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium. AB - Mutations in RPGRIP1L result in severe human diseases called ciliopathies. To unravel the molecular function of RPGRIP1L, we analyzed Rpgrip1l(-/-) mouse embryos, which display a ciliopathy phenotype and die, at the latest, around birth. In these embryos, cilia-mediated signaling was severely disturbed. Defects in Shh signaling suggested that the Rpgrip1l deficiency causes an impairment of protein degradation and protein processing. Indeed, we detected a cilia-dependent decreased proteasomal activity in the absence of Rpgrip1l. We found different proteasomal components localized to cilia and identified Psmd2, a component of the regulatory proteasomal 19S subunit, as an interaction partner for Rpgrip1l. Quantifications of proteasomal substrates demonstrated that Rpgrip1l regulates proteasomal activity specifically at the basal body. Our study suggests that Rpgrip1l controls ciliary signaling by regulating the activity of the ciliary proteasome via Psmd2. PMID- 26150392 TI - Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves. AB - Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease. PMID- 26150393 TI - A network of assembly factors is involved in remodeling rRNA elements during preribosome maturation. PMID- 26150394 TI - Social networks and social norms are associated with obesity treatment outcomes. AB - OBJECTIVE: To examine whether overweight social network members and normative influence for obesity are associated with weight loss outcomes during obesity treatment. METHODS: Participants (N = 214) in a behavioral weight loss trial reported (a) the weight status of various members of their social network and (b) the level of obesogenic normative influence within their social network. Weight was objectively assessed before and after treatment. RESULTS: At baseline, participants with partners and best friends who were overweight and those with more children and relatives who were overweight had higher BMIs (P's < 0.03). However, social norms for obesity were not associated with baseline BMI. During treatment, participants lost an average of 4.4% of initial body weight, and social influence factors were adversely associated with weight loss outcomes. Having more casual friends who were overweight at baseline and being part of a social network with stronger social norms for unhealthy eating predicted poorer weight losses (P's < 0.023). Remaining social influence factors and changes in social influence were not associated with treatment outcomes. CONCLUSIONS: Whereas weight status may "cluster" in social networks, only weight status of casual friends and normative influence for unhealthy eating were associated with obesity treatment outcomes. PMID- 26150395 TI - Hereditary diffuse gastric cancer--An overview. AB - The incidence of gastric cancer varies by up to ten fold throughout the world, and the geographic distribution of hereditary cases is not well explored. Familial clustering is seen in 10% of cases, and approximately 3% of all gastric cancers develop due to hereditary diffuse gastric cancer (HDGC). In this review, the characteristics of HDGC are presented according to molecular particularities, geographic distribution, and other parameters. Based on our experience and the data from the literature, we discuss the possibility of applying a mutation signature (spectrum) study and adductomic approaches to a comparative carcinogenesis of HDGC. We also provide a comprehensive, up-to-date review of genetic counseling and criteria for screening and surveillance of eligible families. PMID- 26150396 TI - Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass. AB - We report a case of a 62-year-old man with concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma. Computed tomography revealed a 5.5-cm anterior mediastinal mass, and surgical resection was performed. Histologically, the mass showed concurrent thymoma (type AB), thymic carcinoma, and T lymphoblastic leukemia/lymphoma. Lymphoma cells infiltrated in the left lung, pulmonary hilar lymph nodes, and involved bone marrow. The patient underwent chemotherapy for T lymphoblastic leukemia/lymphoma and achieved remission. One year after surgery, he remains free of both thymoma and thymic carcinoma, and T lymphoblastic leukemia/lymphoma remains complete remission under maintenance therapy. Thymoma and T lymphoblastic leukemia/lymphoma can combine in the same mass, although this is quite rare. At the time of the diagnosis of thymoma, additional attention should be directed toward lymphocytes in the background. PMID- 26150397 TI - Boron-Catalyzed N-Alkylation of Amines using Carboxylic Acids. AB - A boron-based catalyst was found to catalyze the straightforward alkylation of amines with readily available carboxylic acids in the presence of silane as the reducing agent. Various types of primary and secondary amines can be smoothly alkylated with good selectivity and good functional-group compatibility. This metal-free amine alkylation was successfully applied to the synthesis of three commercial medicinal compounds, Butenafine, Cinacalcet. and Piribedil, in a one pot manner without using any metal catalysts. PMID- 26150398 TI - The photosensitivity of carbon quantum dots/CuAlO2 films composites. AB - Carbon quantum dots/CuAlO2 films were prepared by a simple route through which CuAlO2 films prepared by sol-gel on crystal quartz substrates were composited with carbon quantum dots on their surface. The characterization results indicated that CuAlO2 films were well combined with carbon quantum dots. The photoconductivity of carbon quantum dots/CuAlO2 films was investigated under illumination and darkness switching, and was demonstrated to be significantly enhanced compared with CuAlO2 films. Through analysis, this enhancement of photoconductivity was attributed to the carbon quantum dots with unique up converted photoluminescence behavior. PMID- 26150400 TI - Suckling behavior in goitered gazelle: do females invest more in twins or singletons? AB - The mother-offspring social unit is a universal feature in the social life of all mammals and nursing is the most direct and vital component of maternal investment in young. Living in diverse environments, various ungulate species have different strategies for rearing offspring, from bearing a single, relatively large newborn and supplying only limited amounts of milk, to bearing several relatively small newborns with intensive post-partum lactation. In this paper, we consider the rearing strategy of goitered gazelle with a focus on suckling behavior, which, until now, has never been a subject of special investigation. Adult females of this species in their reproductive prime typically bear twins when environmental conditions are favorable, but the proportion of singletons increases when conditions are unfavorable. We expected that in goitered gazelles suckling intensity would be maximal during the first weeks after birth, and then decrease with the growth of the young; we also expected that twins would demand more energy, but receive significantly less maternal investment per young than singletons. We found that, indeed, suckling behavior had similar dynamics as typical of all bovid species, but our expectation for less maternal investment in twins vs. singletons was wrong. In reality, female goitered gazelles suckled twins significantly more intensively and terminated suckling less often compared to singletons. We concluded that in favorable situations females of high quality have the ability to show significantly more maternal investment in each twin, while singletons are typically born to weaker females. This ability of females to produce mostly twins allows goitered gazelles to take advantage of any favorable opportunity to quickly increase their population in an environment with unpredictable and abrupt yearly changes typical of the arid regions of Central Asia. PMID- 26150399 TI - Prevalence and factors associated with smoking tobacco among men recently released from prison in California: A cross-sectional study. AB - BACKGROUND: Over 1.5 million people are incarcerated in state and federal correctional facilities in the United States. Formerly incarcerated men have significantly higher rates of mortality and morbidity than the general population, disparities that have been partially attributed to higher rates of tobacco smoking-related illnesses such as cardiovascular disease, pulmonary disease and cancer. METHODS: We compared the prevalence of smoking tobacco in a sample of 172 men who were released from California state prisons to Oakland and San Francisco between 2009 and 2011 to sub-populations of respondents to the 2009 California Health Interview Survey (CHIS). Using logistic regression, we analyzed the association between lifetime history of incarceration and self-reported smoking status. RESULTS: Seventy-four percent of men recently released from prison reported being current tobacco smokers. The prevalence of smoking in a demographically similar group of men in the CHIS was 24%. We found in bivariate analysis that each additional five years of history of incarceration was associated with 1.32 times greater odds of smoking (95% CI 1.02 to 1.71). Illicit substance use was associated with a 2.47 higher adjusted odds of smoking (95% CI 1.29 to 5.39). In the multivariate model adjusting for age, income, substance use and mental health, every five years of incarceration was associated with 1.23 greater odds of smoking (95% CI 0.94 to 1.63) which was not statistically significant. CONCLUSIONS: Given the high prevalence of smoking tobacco among former prisoners and the underlying high tobacco-related mortality rates, these findings suggest that a history of incarceration may be an important determinant of smoking. Prison and parole systems may be important potential settings for smoking-cessation interventions. PMID- 26150402 TI - Anisotropic diffraction of bulk acoustic wave beams in lithium niobate. AB - The formalism of planar diffraction tensor was applied to the analysis of anisotropy of bulk acoustic wave diffraction and to build a full map of anisotropic diffractional coefficients for three bulk acoustic wave modes propagating in lithium niobate. For arbitrary propagation direction the diffractional coefficients derived allow estimation of ultrasonic beam divergence in far-field. Analysis of obtained data revealed that the maxima of acousto-optic figure of merit for anisotropic diffraction in the YZ plane correspond to moderate diffractional spreading of the beams exceeding isotropic diffraction 2-3 times. PMID- 26150401 TI - Acoustic tweezers for studying intracellular calcium signaling in SKBR-3 human breast cancer cells. AB - Extracellular matrix proteins such as fibronectin (FNT) play crucial roles in cell proliferation, adhesion, and migration. For better understanding of these associated cellular activities, various microscopic manipulation tools have been used to study their intracellular signaling pathways. Recently, it has appeared that acoustic tweezers may possess similar capabilities in the study. Therefore, we here demonstrate that our newly developed acoustic tweezers with a high frequency lithium niobate ultrasonic transducer have potentials to study intracellular calcium signaling by FNT-binding to human breast cancer cells (SKBR 3). It is found that intracellular calcium elevations in SKBR-3 cells, initially occurring on the microbead-contacted spot and then eventually spreading over the entire cell, are elicited by attaching an acoustically trapped FNT-coated microbead. Interestingly, they are suppressed by either extracellular calcium elimination or phospholipase C (PLC) inhibition. Hence, this suggests that our acoustic tweezers may serve as an alternative tool in the study of intracellular signaling by FNT-binding activities. PMID- 26150403 TI - Improvement of Heart Redox States Contributes to the Beneficial Effects of Selenium Against Penconazole-Induced Cardiotoxicity in Adult Rats. AB - The present study was performed to evaluate the protective effect of selenium (Se) against penconazole (PEN)-induced oxidative stress in the cardiac tissue of adult rats. Male Wistar rats were divided into four groups of six each. The first group represented the controls. For the second group (PEN), no treatment was performed during the first 6 days, and then, the rats received intraperitoneally 67 mg/kg body weight (bw) of PEN every 2 days from day 7 until day 15, the sacrifice day. For the third group (Se + PEN), Se was administered daily through the diet at a dose of 0.5 mg/kg of diet for 15 days. Rats of this group received also every 2 days PEN (67 mg/kg bw) from day 7 until day 15. The fourth group (Se) received daily, through the diet, Se (0.5 mg/Kg of diet) during 15 days. Our results showed that Se reduced significantly the elevated cardiac levels of malondialdehyde and protein carbonyl following PEN treatment, and attenuated DNA fragmentation induced by this fungicide. In addition, Se modulated the alterations of antioxidant status: enzymatic (superoxide dismutase, glutathione peroxidase, and catalase) and nonenzymatic (glutathione and vitamin C) antioxidants in the heart of PEN-treated rats. This trace element was also able to alleviate perturbations of lipid profile. The protective effect of selenium was further evident through the histopathological changes produced by PEN in the heart tissue. Taken together, our results indicated that Se might be beneficial against PEN-induced cardiac oxidative damage in rats. PMID- 26150404 TI - Effect of Selenium Deficiency on Phosphorylation of the AMPK Pathway in Rats. AB - Selenium is an important trace element for human health. Previous studies have raised concern that dietary selenium intake may change energy metabolism. AMP activated protein kinase (AMPK) is a sensor of energy status that controls cellular energy homeostasis. We aimed to determine the effect of selenium on the phosphorylation of AMPK pathway between Se-deficient and normal Sprague-Dawley rats. Twenty-four weaning rats were fed either a Se-deficient diet (0.02 mg Se/kg) or a standard diet (0.18 mg Se/kg). After 109 days, total serum levels of non-esterified fatty acid and total amino acids were significantly higher and the serum insulin concentration was significantly lower in Se-deficient rats than in healthy controls. Selenium concentration and the activity of glutathione peroxidase (GPx) in myocardial tissue were significantly lower in Se-deficient rats. Importantly, mRNA levels of acetyl-CoA carboxylase beta (ACACB), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha), and protein levels of p-AMPKalpha were increased in the Se-deficient group compared to normal controls (p < 0.05). In conclusion, our results suggest that selenium deficiency induces changes in metabolic and molecular parameters involved in energy metabolism in the AMPK pathway. PMID- 26150405 TI - Zinc-Dithizone Complex Engineered Upconverting Nanosensors for the Detection of Hypochlorite in Living Cells. AB - Current chemo/biosensors for hypochlorous acid or hypochlorite detections are usually limited to the submicromolar level because of their insufficient sensitivity, which is a problem because the concentrations in biological matrices is generally on the nanomolar scale or even lower. Developing a probe with a high enough sensitivity remains a challenge. Using the minimal background fluorescence of upconversion nanocrystals to our advantage, we herein report on an energy transfer mechanism-based upconversion luminescent nanosensor for the sensitive and selective detection of hypochlorite in aqueous solution. In this nanosensor water-dispersible upconversion nanoparticles act as the energy donor and a novel hypochlorite-responsive coordination complex Zn(DZ)3 is employed as the energy acceptor. The quenched upconversion luminescence, induced by the Zn(DZ)3 complex, can be efficiently recovered after addition of hypochlorite through the selective oxidative breakage of the Zn-S-C bonds in the Zn(DZ)3 complex, which was verified by mass spectrometry. The detection limit for hypochlorite of this sensing system is as low as 3 nM. Furthermore, this newly coordination-complex engineered upconversion nanosensor is successfully applied to image different amounts of exogenous hypochlorite in living HeLa cells. PMID- 26150406 TI - Effect of epitaxial strain on tunneling electroresistance in ferroelectric tunnel junctions. AB - We report the effect of compressive strain on the tunneling electroresistance (TER) effect in BaTiO3/SrRuO3 (BTO/SRO) heterostructures. We find that epitaxial strain imposed by the mismatch of NdGaO3 and SrTiO3 lattice parameters with the BTO and SRO layers improves ferroelectric polarization of BTO and concurrently promotes the metallicity of the SRO films. While the enhanced polarization is beneficial for the TER magnitude, the reduced asymmetry in the tunneling barrier due to the shortened screening length of SRO is detrimental for the effect. Thus, a combined effect of strain on the polarization of the ferroelectric barrier and the screening properties of the electrodes needs to be taken into account when considering and predicting the TER effect in ferroelectric tunnel junctions. PMID- 26150407 TI - Decreased faux addenda following standardisation of pathologist practice. AB - AIMS: We wanted to improve the quality of histopathology addenda and amendments by introducing standardised nomenclature and procedures. METHODS: We standardised amendment and addenda definitions, implemented a pathologist visual work tool, and evaluated and quantitated all amendments and addenda for 3 months prior to implementation and 17 months after. RESULTS: In the 3-month pre-intervention period, 32 of 979 addenda (3.3%) were misused and 18 of 98 amendments (18.4%) were incorrectly classified. In the 17-month post-intervention period, 57 of 5906 addenda (1.0%) were misused and 54 of 752 amendments (7.2%) were incorrectly classified. These differences were statistically significant (p<0.0001). CONCLUSIONS: The introduction of standardised nomenclature and a visual work tool significantly improved the quality of histopathology addenda and amendments. PMID- 26150409 TI - Tuning the polarized quantum phonon transmission in graphene nanoribbons. AB - We propose systems that allow a tuning of the phonon transmission function T(omega) in graphene nanoribbons by using C(13) isotope barriers, antidot structures, and distinct boundary conditions. Phonon modes are obtained by an interatomic fifth-nearest neighbor force-constant model (5NNFCM) and T(omega) is calculated using the non-equilibrium Green's function formalism. We show that by imposing partial fixed boundary conditions it is possible to restrict contributions of the in-plane phonon modes to T(omega) at low energy. On the contrary, the transmission functions of out-of-plane phonon modes can be diminished by proper antidot or isotope arrangements. In particular, we show that a periodic array of them leads to sharp dips in the transmission function at certain frequencies [Formula: see text] which can be pre-defined as desired by controlling their relative distance and size. With this, we demonstrated that by adequate engineering it is possible to govern the magnitude of the ballistic transmission functions [Formula: see text] in graphene nanoribbons. We discuss the implications of these results in the design of controlled thermal transport at the nanoscale as well as in the enhancement of thermo-electric features of graphene-based materials. PMID- 26150408 TI - Reduction of multiple pregnancies in the advanced maternal age population after implementation of an elective single embryo transfer policy coupled with enhanced embryo selection: pre- and post-intervention study. AB - STUDY QUESTION: Is an elective single-embryo transfer (eSET) policy an efficient approach for women aged >35 years when embryo selection is enhanced via blastocyst culture and preimplantation genetic screening (PGS)? SUMMARY ANSWER: Elective SET coupled with enhanced embryo selection using PGS in women older than 35 years reduced the multiple pregnancy rates while maintaining the cumulative success rate of the IVF programme. WHAT IS KNOWN ALREADY: Multiple pregnancies mean an increased risk of premature birth and perinatal death and occur mainly in older patients when multiple embryos are transferred to increase the chance of pregnancy. A SET policy is usually recommended in cases of good prognosis patients, but no general consensus has been reached for SET application in the advanced maternal age (AMA) population, defined as women older than 35 years. Our objective was to evaluate the results in terms of efficacy, efficiency and safety of an eSET policy coupled with increased application of blastocyst culture and PGS for this population of patients in our IVF programme. STUDY DESIGN, SIZE, DURATION: In January 2013, a multidisciplinary intervention involving optimization of embryo selection procedure and introduction of an eSET policy in an AMA population of women was implemented. This is a retrospective 4-year (January 2010-December 2013) pre- and post-intervention analysis, including 1161 and 499 patients in the pre- and post-intervention period, respectively. The primary outcome measures were the cumulative delivery rate (DR) per oocyte retrieval cycle and multiple DR. PARTICIPANTS/MATERIALS, SETTING, METHODS: Surplus oocytes and/or embryos were vitrified during the entire study period. In the post-intervention period, all couples with good quality embryos and less than two previous implantation failures were offered eSET. Embryo selection was enhanced by blastocyst culture and PGS (blastocyst stage biopsy and 24 chromosomal screening). Elective SET was also applied in cryopreservation cycles. MAIN RESULTS AND THE ROLE OF CHANCE: Patient and cycle characteristics were similar in the pre- and post-intervention groups [mean (SD) female age: 39.6 +/- 2.1 and 39.4 +/- 2.2 years; range 36-44] as assessed by logistic regression. A total of 1609 versus 574 oocyte retrievals, 937 versus 350 embryo warming and 138 versus 27 oocyte warming cycles were performed in the pre- and post-intervention periods, respectively, resulting in 1854 and 508 embryo transfers, respectively. In the post-intervention period, 289 cycles were blastocyst stage with (n = 182) or without PGS (n = 107). A mean (SD) number of 2.9 +/- 1.1 (range 1-4) and 1.4 +/- 0.8 (range 1-3) embryos were transferred pre- and post-intervention, respectively (P < 0.01) and similar cumulative clinical pregnancy rates per transfer and per cycle were obtained: 26.8, 30.9% and 29.7, 26.3%, respectively. The total DR per oocyte retrieval cycle (21.0 and 20.4% pre- and post intervention, respectively) defined as efficacy was not affected by the intervention [odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.7-1.1; P = 0.23]. However, a significantly increased live birth rate per transferred embryo (defined as efficiency) was observed in the post-intervention group 17.0 versus 10.6% (P < 0.01). Multiple DRs decreased from 21.0 in the preintervention to 6.8% in the post-intervention group (OR = 0.3. 95% CI = 0.1-0.7; P < 0.01). LIMITATIONS, REASONS FOR CAUTION: In this study, the suitability of SET was assessed in individual women on the basis of both clinical and embryological prognostic factors and was not standardized. For the described eSET strategy coupled with an enhanced embryo selection policy, an optimized culture system, cryopreservation and aneuploidy screening programme is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Owing to the increased maternal morbidity and perinatal complications related to multiple pregnancies, it is recommended to extend the eSET policy to the AMA population. As shown in this study, enhanced embryo selection procedures might allow a reduction in the number of embryos transferred and the number of transfers to be performed without affecting the total efficacy of the treatment but increasing efficiency and safety. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: None. PMID- 26150410 TI - Malassezia Pneumonia: A Rare Complication of Parenteral Nutrition Therapy. AB - Malassezia species (formerly known as Pityrosporum) are part of normal human skin flora and have been associated with benign dermatologic conditions, such as seborrheic dermatitis and tinea versicolor. In rare cases, however, Malassezia has been associated with systemic disease in immunocompromised patients and infants in the neonatal intensive care unit. Malassezia species require long chain fatty acids for growth and therefore have a known predilection for individuals receiving lipid containing intravenous parenteral nutrition (PN). Systemic infections are characterized by prolonged fevers and illness but can include nonspecific signs and symptoms. We present the diagnosis and management of a rare case of an immunocompetent, nonneonatal, PN-dependent child with Malassezia furfur pneumonia. PMID- 26150411 TI - Should We PERMIT Systematic Underfeeding in All Intensive Care Unit Patients? Integrating the Results of the PERMIT Study in Our Clinical Practice Guidelines. PMID- 26150412 TI - High Protein Intake Does Not Prevent Low Plasma Levels of Conditionally Essential Amino Acids in Very Preterm Infants Receiving Parenteral Nutrition. AB - BACKGROUND: We have shown that increasing protein intake using a standardized, concentrated, added macronutrients parenteral (SCAMP) nutrition regimen improves head growth in very preterm infants (VPIs) compared with a control parenteral nutrition (PN) regimen. VPIs are at risk of conditionally essential amino acid (CEAA) deficiencies because of current neonatal PN amino acid (AA) formulations. We hypothesized that the SCAMP regimen would prevent low plasma levels of CEAAs. AIM: To compare the plasma AA profiles at approximately day 9 of life in VPIs receiving SCAMP vs a control PN regimen. METHODS: VPIs (<29 weeks' gestation) were randomized to receive SCAMP (30% more PN AA) or a control regimen. Data were collected to measure parenteral and enteral protein, energy, and individual AA intake and the first plasma AA profile. Plasma profiles of the 20 individual protogenic AA levels were measured using ion exchange chromatography. RESULTS: Plasma AA profiles were obtained at median (interquartile range [IQR]) age of 9 (8-10) days in both SCAMP (n = 59) and control (n = 67) groups after randomizing 150 VPIs. Median (IQR) plasma levels of individual essential AAs were higher than the reference population mean (RPM) in both groups, especially for threonine. SCAMP infants had higher plasma levels of essential AAs than did the controls. Median (IQR) plasma levels of glutamine, arginine, and cysteine (CEAAs) were lower than the RPM in both groups. CONCLUSION: Plasma AA levels in PN-dependent VPIs indicate there is an imbalance in essential and CEAA provision in neonatal PN AA formulations that is not improved by increasing protein intake. PMID- 26150413 TI - Interplay between Gliotoxin Resistance, Secretion, and the Methyl/Methionine Cycle in Aspergillus fumigatus. AB - Mechanistic studies on gliotoxin biosynthesis and self-protection in Aspergillus fumigatus, both of which require the gliotoxin oxidoreductase GliT, have revealed a rich landscape of highly novel biochemistries, yet key aspects of this complex molecular architecture remain obscure. Here we show that an A. fumigatus DeltagliA strain is completely deficient in gliotoxin secretion but still retains the ability to efflux bisdethiobis(methylthio)gliotoxin (BmGT). This correlates with a significant increase in sensitivity to exogenous gliotoxin because gliotoxin trapped inside the cell leads to (i) activation of the gli cluster, as disabling gli cluster activation, via gliZ deletion, attenuates the sensitivity of an A. fumigatus DeltagliT strain to gliotoxin, thus implicating cluster activation as a factor in gliotoxin sensitivity, and (ii) increased methylation activity due to excess substrate (dithiol gliotoxin) for the gliotoxin bis thiomethyltransferase GtmA. Intracellular dithiol gliotoxin is oxidized by GliT and subsequently effluxed by GliA. In the absence of GliA, gliotoxin persists in the cell and is converted to BmGT, with levels significantly higher than those in the wild type. Similarly, in the DeltagliT strain, gliotoxin oxidation is impeded, and methylation occurs unchecked, leading to significant S adenosylmethionine (SAM) depletion and S-adenosylhomocysteine (SAH) overproduction. This in turn significantly contributes to the observed hypersensitivity of gliT-deficient A. fumigatus to gliotoxin. Our observations reveal a key role for GliT in preventing dysregulation of the methyl/methionine cycle to control intracellular SAM and SAH homeostasis during gliotoxin biosynthesis and exposure. Moreover, we reveal attenuated GliT abundance in the A. fumigatus DeltagliK strain, but not the DeltagliG strain, following exposure to gliotoxin, correlating with relative sensitivities. Overall, we illuminate new systems interactions that have evolved in gliotoxin-producing, compared to gliotoxin-naive, fungi to facilitate their cellular presence. PMID- 26150414 TI - Ineffective Phosphorylation of Mitogen-Activated Protein Kinase Hog1p in Response to High Osmotic Stress in the Yeast Kluyveromyces lactis. AB - When treated with a hyperosmotic stimulus, Kluyveromyces lactis cells respond by activating the mitogen-activated protein kinase (MAPK) K. lactis Hog1 (KlHog1) protein via two conserved branches, SLN1 and SHO1. Mutants affected in only one branch can cope with external hyperosmolarity by activating KlHog1p by phosphorylation, except for single DeltaKlste11 and DeltaKlste50 mutants, which showed high sensitivity to osmotic stress, even though the other branch (SLN1) was intact. Inactivation of both branches by deletion of KlSHO1 and KlSSK2 also produced sensitivity to high salt. Interestingly, we have observed that in DeltaKlste11 and DeltaKlsho1 DeltaKlssk2 mutants, which exhibit sensitivity to hyperosmotic stress, and contrary to what would be expected, KlHog1p becomes phosphorylated. Additionally, in mutants lacking both MAPK kinase kinases (MAPKKKs) present in K. lactis (KlSte11p and KlSsk2p), the hyperosmotic stress induced the phosphorylation and nuclear internalization of KlHog1p, but it failed to induce the transcriptional expression of KlSTL1 and the cell was unable to grow in high-osmolarity medium. KlHog1p phosphorylation via the canonical HOG pathway or in mutants where the SHO1 and SLN1 branches have been inactivated requires not only the presence of KlPbs2p but also its kinase activity. This indicates that when the SHO1 and SLN1 branches are inactivated, high-osmotic stress conditions activate an independent input that yields active KlPbs2p, which, in turn, renders KlHog1p phosphorylation ineffective. Finally, we found that KlSte11p can alleviate the sensitivity to hyperosmotic stress displayed by a DeltaKlsho1 DeltaKlssk2 mutant when it is anchored to the plasma membrane by adding the KlSho1p transmembrane segments, indicating that this chimeric protein can substitute for KlSho1p and KlSsk2p. PMID- 26150415 TI - Conserved Mode of Interaction between Yeast Bro1 Family V Domains and YP(X)nL Motif-Containing Target Proteins. AB - Yeast Bro1 and Rim20 belong to a family of proteins which possess a common architecture of Bro1 and V domains. Alix and His domain protein tyrosine phosphatase (HD-PTP), mammalian Bro1 family proteins, bind YP(X)nL (n = 1 to 3) motifs in their target proteins through their V domains. In Alix, the Phe residue, which is located in the hydrophobic groove of the V domain, is critical for binding to the YP(X)nL motif. Although the overall sequences are not highly conserved between mammalian and yeast V domains, we show that the conserved Phe residue in the yeast Bro1 V domain is important for binding to its YP(X)nL containing target protein, Rfu1. Furthermore, we show that Rim20 binds to its target protein Rim101 through the interaction between the V domain of Rim20 and the YPIKL motif of Rim101. The mutation of either the critical Phe residue in the Rim20 V domain or the YPIKL motif of Rim101 affected the Rim20-mediated processing of Rim101. These results suggest that the interactions between V domains and YP(X)nL motif-containing proteins are conserved from yeast to mammalian cells. Moreover, the specificities of each V domain to their target protein suggest that unidentified elements determine the binding specificity. PMID- 26150416 TI - A Cyclic GMP-Dependent K+ Channel in the Blastocladiomycete Fungus Blastocladiella emersonii. AB - Phototaxis in flagellated zoospores of the aquatic fungus Blastocladiella emersonii depends on a novel photosensor, Blastocladiella emersonii GC1 (BeGC1), comprising a type I (microbial) rhodopsin fused to a guanylyl cyclase catalytic domain, that produces the conserved second messenger cyclic GMP (cGMP). The rapid and transient increase in cGMP levels during the exposure of zoospores to green light was shown to be necessary for phototaxis and dependent on both rhodopsin function and guanylyl cyclase activity. It is noteworthy that BeGC1 was localized to the zoospore eyespot apparatus, in agreement with its role in the phototactic response. A putative cyclic nucleotide-gated channel (BeCNG1) was also identified in the genome of the fungus and was implicated in flagellar beating via the action of a specific inhibitor (l-cis-diltiazem) that compromised zoospore motility. Here we show that B. emersonii expresses a K(+) channel that is activated by cGMP. The use of specific channel inhibitors confirmed the activation of the channel by cGMP and its K(+) selectivity. These characteristics are consistent with the function of an ion channel encoded by the BeCNG1 gene. Other blastocladiomycete fungi, such as Allomyces macrogynus and Catenaria anguillulae, possess genes encoding a similar K(+) channel and the rhodopsin guanylyl cyclase fusion protein, while the genes encoding both these proteins are absent in nonflagellated fungi. The presence of these genes as a pair seems to be an exclusive feature of blastocladiomycete fungi. Taken together, these data demonstrate that the B. emersonii cGMP-activated K(+) channel is involved in the control of zoospore motility, most probably participating in the cGMP-signaling pathway for the phototactic response of the fungus. PMID- 26150417 TI - Characterization of Virulence-Related Phenotypes in Candida Species of the CUG Clade. AB - Candida species cause a variety of mucosal and invasive infections and are, collectively, the most important human fungal pathogens in the developed world. The majority of these infections result from a few related species within the "CUG clade," so named because they use a nonstandard translation for that codon. Some members of the CUG clade, such as Candida albicans, present significant clinical problems, whereas others, such as Candida (Meyerozyma) guilliermondii, are uncommon in patients. The differences in incidence rates are imperfectly correlated with virulence in animal models of infection, but comparative analyses that might provide an explanation for why some species are effective pathogens and others are not have been rare or incomplete. To better understand the phenotypic basis for these differences, we characterized eight CUG clade species- C. albicans, C. dubliniensis, C. tropicalis, C. parapsilosis, Clavispora lusitaniae, M. guilliermondii, Debaryomyces hansenii, and Lodderomyces elongisporus--for host-relevant phenotypes, including nutrient utilization, stress tolerance, morphogenesis, interactions with phagocytes, and biofilm formation. Two species deviated from expectations based on animal studies and human incidence. C. dubliniensis was quite robust, grouping in nearly all assays with the most virulent species, C. albicans and C. tropicalis, whereas C. parapsilosis was substantially less fit than might be expected from its clinical importance. These findings confirm the utility of in vitro measures of virulence and provide insight into the evolution of virulence in the CUG clade. PMID- 26150418 TI - UV induced ubiquitination of the yeast Rad4-Rad23 complex promotes survival by regulating cellular dNTP pools. AB - Regulating gene expression programmes is a central facet of the DNA damage response. The Dun1 kinase protein controls expression of many DNA damage induced genes, including the ribonucleotide reductase genes, which regulate cellular dNTP pools. Using a combination of gene expression profiling and chromatin immunoprecipitation, we demonstrate that in the absence of DNA damage the yeast Rad4-Rad23 nucleotide excision repair complex binds to the promoters of certain DNA damage response genes including DUN1, inhibiting their expression. UV radiation promotes the loss of occupancy of the Rad4-Rad23 complex from the regulatory regions of these genes, enabling their induction and thereby controlling the production of dNTPs. We demonstrate that this regulatory mechanism, which is dependent on the ubiquitination of Rad4 by the GG-NER E3 ligase, promotes UV survival in yeast cells. These results support an unanticipated regulatory mechanism that integrates ubiquitination of NER DNA repair factors with the regulation of the transcriptional response controlling dNTP production and cellular survival after UV damage. PMID- 26150420 TI - Microbial species delineation using whole genome sequences. AB - Increased sequencing of microbial genomes has revealed that prevailing prokaryotic species assignments can be inconsistent with whole genome information for a significant number of species. The long-standing need for a systematic and scalable species assignment technique can be met by the genome-wide Average Nucleotide Identity (gANI) metric, which is widely acknowledged as a robust measure of genomic relatedness. In this work, we demonstrate that the combination of gANI and the alignment fraction (AF) between two genomes accurately reflects their genomic relatedness. We introduce an efficient implementation of AF,gANI and discuss its successful application to 86.5M genome pairs between 13,151 prokaryotic genomes assigned to 3032 species. Subsequently, by comparing the genome clusters obtained from complete linkage clustering of these pairs to existing taxonomy, we observed that nearly 18% of all prokaryotic species suffer from anomalies in species definition. Our results can be used to explore central questions such as whether microorganisms form a continuum of genetic diversity or distinct species represented by distinct genetic signatures. We propose that this precise and objective AF,gANI-based species definition: the MiSI (Microbial Species Identifier) method, be used to address previous inconsistencies in species classification and as the primary guide for new taxonomic species assignment, supplemented by the traditional polyphasic approach, as required. PMID- 26150419 TI - Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation. AB - Protozoan parasites of the genus Leishmania are the etiological agents of leishmaniasis, a group of diseases with a worldwide incidence of 0.9-1.6 million cases per year. We used RNA-seq to conduct a high-resolution transcriptomic analysis of the global changes in gene expression and RNA processing events that occur as L. major transforms from non-infective procyclic promastigotes to infective metacyclic promastigotes. Careful statistical analysis across multiple biological replicates and the removal of batch effects provided a high quality framework for comprehensively analyzing differential gene expression and transcriptome remodeling in this pathogen as it acquires its infectivity. We also identified precise 5' and 3' UTR boundaries for a majority of Leishmania genes and detected widespread alternative trans-splicing and polyadenylation. An investigation of possible correlations between stage-specific preferential trans splicing or polyadenylation sites and differentially expressed genes revealed a lack of systematic association, establishing that differences in expression levels cannot be attributed to stage-regulated alternative RNA processing. Our findings build on and improve existing expression datasets and provide a substantially more detailed view of L. major biology that will inform the field and potentially provide a stronger basis for drug discovery and vaccine development efforts. PMID- 26150421 TI - Recovery of the poisoned topoisomerase II for DNA religation: coordinated motion of the cleavage core revealed with the microsecond atomistic simulation. AB - Type II topoisomerases resolve topological problems of DNA double helices by passing one duplex through the reversible double-stranded break they generated on another duplex. Despite the wealth of information in the cleaving operation, molecular understanding of the enzymatic DNA ligation remains elusive. Topoisomerase poisons are widely used in anti-cancer and anti-bacterial therapy and have been employed to entrap the intermediates of topoisomerase IIbeta with religatable DNA substrate. We removed drug molecules from the structure and conducted molecular dynamics simulations to investigate the enzyme-mediated DNA religation. The drug-unbound intermediate displayed transitions toward the resealing-compliant configuration: closing distance between the cleaved DNA termini, B-to-A transformation of the double helix, and restoration of the metal binding motif. By mapping the contact configurations and the correlated motions between enzyme and DNA, we identified the indispensable role of the linker preceding winged helix domain (WHD) in coordinating the movements of TOPRIM, the nucleotide-binding motifs, and the bound DNA substrate during gate closure. We observed a nearly vectorial transition in the recovery of the enzyme and identified the previously uncharacterized roles of Asn508 and Arg677 in DNA rejoining. Our findings delineate the dynamic mechanism of the DNA religation conducted by type II topoisomerases. PMID- 26150422 TI - Structural and functional studies of the Mycobacterium tuberculosis VapBC30 toxin antitoxin system: implications for the design of novel antimicrobial peptides. AB - Toxin-antitoxin (TA) systems play important roles in bacterial physiology, such as multidrug tolerance, biofilm formation, and arrest of cellular growth under stress conditions. To develop novel antimicrobial agents against tuberculosis, we focused on VapBC systems, which encompass more than half of TA systems in Mycobacterium tuberculosis. Here, we report that theMycobacterium tuberculosis VapC30 toxin regulates cellular growth through both magnesium and manganese ion dependent ribonuclease activity and is inhibited by the cognate VapB30 antitoxin. We also determined the 2.7-A resolution crystal structure of the M. tuberculosis VapBC30 complex, which revealed a novel process of inactivation of the VapC30 toxin via swapped blocking by the VapB30 antitoxin. Our study on M. tuberculosis VapBC30 leads us to design two kinds of VapB30 and VapC30-based novel peptides which successfully disrupt the toxin-antitoxin complex and thus activate the ribonuclease activity of the VapC30 toxin. Our discovery herein possibly paves the way to treat tuberculosis for next generation. PMID- 26150423 TI - Structural basis of the mercury(II)-mediated conformational switching of the dual function transcriptional regulator MerR. AB - The mer operon confers bacterial resistance to inorganic mercury (Hg(2+)) and organomercurials by encoding proteins involved in sensing, transport and detoxification of these cytotoxic agents. Expression of the mer operon is under tight control by the dual-function transcriptional regulator MerR. The metal free, apo MerR binds to the mer operator/promoter region as a repressor to block transcription initiation, but is converted into an activator upon Hg(2+)-binding. To understand how MerR interacts with Hg(2+) and how Hg(2+)-binding modulates MerR function, we report here the crystal structures of apo and Hg(2+)-bound MerR from Bacillus megaterium, corresponding respectively to the repressor and activator conformation of MerR. To our knowledge, the apo-MerR structure represents the first visualization of a MerR family member in its intact and inducer-free form. And the Hg(2+)-MerR structure offers the first view of a triligated Hg(2+)-thiolate center in a metalloprotein, confirming that MerR binds Hg(2+) via trigonal planar coordination geometry. Structural comparison revealed the conformational transition of MerR is coupled to the assembly/disassembly of a buried Hg(2+) binding site, thereby providing a structural basis for the Hg(2+) mediated functional switching of MerR. The pronounced Hg(2+)-induced repositioning of the MerR DNA-binding domains suggests a plausible mechanism for the transcriptional regulation of the mer operon. PMID- 26150424 TI - Generation of supercoils in nicked and gapped DNA drives DNA unknotting and postreplicative decatenation. AB - Due to the helical structure of DNA the process of DNA replication is topologically complex. Freshly replicated DNA molecules are catenated with each other and are frequently knotted. For proper functioning of DNA it is necessary to remove all of these entanglements. This is done by DNA topoisomerases that pass DNA segments through each other. However, it has been a riddle how DNA topoisomerases select the sites of their action. In highly crowded DNA in living cells random passages between contacting segments would only increase the extent of entanglement. Using molecular dynamics simulations we observed that in actively supercoiled DNA molecules the entanglements resulting from DNA knotting or catenation spontaneously approach sites of nicks and gaps in the DNA. Type I topoisomerases, that preferentially act at sites of nick and gaps, are thus naturally provided with DNA-DNA juxtapositions where a passage results in an error-free DNA unknotting or DNA decatenation. PMID- 26150425 TI - Structural heterogeneity and functional diversity of topologically associating domains in mammalian genomes. AB - Recent chromosome conformation capture (3C) derived techniques have revealed that topologically associating domain (TAD) is a pervasive element in chromatin three dimensional (3D) organization. However, there is currently no parameter to quantitatively measure the structural characteristics of TADs, thus obscuring our understanding on the structural and functional differences among TADs. Based on our finding that there exist intrinsic chromatin interaction patterns in TADs, we define a theoretical parameter, called aggregation preference (AP), to characterize TAD structures by capturing the interaction aggregation degree. Applying this defined parameter to 11 Hi-C data sets generated by both traditional and in situ Hi-C experimental pipelines, our analyses reveal that heterogeneous structures exist among TADs, and this structural heterogeneity is significantly correlated to DNA sequences, epigenomic signals and gene expressions. Although TADs can be stable in genomic positions across cell lines, structural comparisons show that a considerable number of stable TADs undergo significantly structural rearrangements during cell changes. Moreover, the structural change of TAD is tightly associated with its transcription remodeling. Altogether, the theoretical parameter defined in this work provides a quantitative method to link structural characteristics and biological functions of TADs, and this linkage implies that chromatin interaction pattern has the potential to mark transcription activity in TADs. PMID- 26150426 TI - The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super enhancers to drive chondrogenesis. AB - SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We use here genome-wide approaches to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio. Using the RCS cell line as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes, we uncover that SOX6 and SOX9 bind thousands of genomic sites, frequently and most efficiently near each other. SOX9 recognizes pairs of inverted SOX motifs, whereas SOX6 favors pairs of tandem SOX motifs. The SOX proteins primarily target enhancers. While binding to a small fraction of typical enhancers, they bind multiple sites on almost all super-enhancers (SEs) present in RCS cells. These SEs are predominantly linked to cartilage-specific genes. The SOX proteins effectively work together to activate these SEs and are required for in vivo expression of their associated genes. These genes encode key regulatory factors, including the SOX trio proteins, and all essential cartilage extracellular matrix components. Chst11, Fgfr3, Runx2 and Runx3 are among many other newly identified SOX trio targets. SOX9 and SOX5/SOX6 thus cooperate genome wide, primarily through SEs, to implement the growth plate chondrocyte differentiation program. PMID- 26150427 TI - Nucleic acid-binding specificity of human FUS protein. AB - FUS, a nuclear RNA-binding protein, plays multiple roles in RNA processing. Five specific FUS-binding RNA sequence/structure motifs have been proposed, but their affinities for FUS have not been directly compared. Here we find that human FUS binds all these sequences with Kd (app) values spanning a 10-fold range. Furthermore, some RNAs that do not contain any of these motifs bind FUS with similar affinity. FUS binds RNA in a length-dependent manner, consistent with a substantial non-specific component to binding. Finally, investigation of FUS binding to different nucleic acids shows that it binds single-stranded DNA with three-fold lower affinity than ssRNA of the same length and sequence, while binding to double-stranded nucleic acids is weaker. We conclude that FUS has quite general nucleic acid-binding activity, with the various proposed RNA motifs being neither necessary for FUS binding nor sufficient to explain its diverse binding partners. PMID- 26150429 TI - The roles of resilience and nonmotor symptoms in adjustment to Parkinson's disease. AB - Resilience contributes to better chronic disease adjustment but is understudied in Parkinson's disease. Although nonmotor symptoms affect quality of life, their effect on other aspects of Parkinson's disease adjustment is less understood. Hierarchical regression analyses from a cross-sectional survey of 138 community dwelling adults with Parkinson's disease (mean (standard deviation) age = 64.15(10.09) years) investigated relationships between nonmotor symptoms and resilience on depression, apathy, life satisfaction, and quality of life. After controlling for demographic variables, functional status, and nonmotor symptoms, resilience was associated with all adjustment variables. Nonmotor symptoms were associated with depression and worse quality of life. Nonmotor symptoms and resilience appear to play critical roles in Parkinson's disease adjustment. PMID- 26150428 TI - Smoking is associated with aggravated kidney injury in Puumala hantavirus-induced haemorrhagic fever with renal syndrome. AB - BACKGROUND: Previous studies indicate that smoking affects the outcome of some infections and is a risk factor for Puumala virus (PUUV) infection. The aim of this study was to assess the effect of smoking on the clinical severity of PUUV infection and the prevalence of smoking in patients with PUUV infection. METHODS: A questionnaire on smoking habits was sent to 494 patients in 2012, who had been treated in Tampere University Hospital, Finland, for serologically confirmed PUUV infection during years 1982-2012. RESULTS: Of all patients, 357 (72%) participated. Maximum plasma creatinine level measured during acute illness was significantly higher in current smokers than in non-smokers (median: 273 versus 184 umol/L, P < 0.001). Current smokers had a higher maximum blood leucocyte count than non-smokers (median: 10.8 versus 8.9 * 10(9)/L, P < 0.001) and they were younger than non-smokers (38 versus 45 years, P < 0.001). There were no differences between current smokers and non-smokers in the other variables reflecting the severity of PUUV infection. Altogether 51% were current smokers at the time of onset of the illness, 57% of males and 36% of females. During these years in Finland, smoking among males in the same aged population has decreased from 33 to 22% and among females, smoking has varied between 14 and 20%. CONCLUSIONS: Smoking is common in patients with PUUV infection. Current smokers suffer from more severe acute kidney injury (AKI) and they have higher leucocyte count than non-smokers in PUUV infection. Smoking cessation decreases the risk of severe AKI to the same level as observed in never-smokers. PMID- 26150430 TI - Concealment, communication and stigma: The perspectives of HIV-positive immigrant Black African men and their partners living in the United Kingdom. AB - This study explored the perspectives of Black men, originally from East Africa, living in the United Kingdom and their partners on what it means to live with diagnosed HIV. This article reports on concealment of HIV-positive status as a strategy adopted by the affected participants to manage the flow of information about their HIV-positive status. Analysis of the data, collected using in-depth interviews involving 23 participants, found widespread selective concealment of HIV-positive status. However, a few respondents had 'come out' publicly about their condition. HIV prevention initiatives should recognise concealment as a vital strategy in managing communication about one's HIV-positive status. PMID- 26150431 TI - The effects of stress inoculation training on perceived stress in pregnant women. AB - A total of 64 pregnant women were assigned into two groups of cases and controls. Both groups filled out the Perceived Stress Scale at pre-test. Cognitive behavioral coping skill training was delivered to the case group. After the end of the intervention, both groups completed the same scale again. The results showed that the mean perceived stress of the cases and controls was 27.77 +/- 6.033 and 18.97 +/- 3.268, respectively (p = 0.001). Therefore, midwives are recommended to plan educational interventions to decrease perceived stress in pregnant women. PMID- 26150432 TI - Adolescents' experiences and perceived (dis)advantages of the three main outlet types for alcohol purchases. AB - Based on the existing literature, relevant determinants of availability for on premises locations, off-premises locations, and the Internet were qualitatively explored and categorized by "experts" consisting of underage alcohol purchasers. In total, 14 focus group discussions were conducted with 94 Dutch adolescents. For on-premises locations, the high prices were perceived as the biggest disadvantage, and the ease to circumvent legal age limits as the biggest advantage. For off-premises locations, the cheap pricing was perceived as the most positive aspect, and the legal age limit as the biggest disadvantage. For online purchases, the waiting time was perceived as the most negative aspect, and the proximity of online stores as the biggest advantage. PMID- 26150433 TI - Trash Talk by Fat: Chemerin as a Reactive Oxygen Species Provocateur in the Vasculature. PMID- 26150434 TI - Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney Disease: Long-Term Cohort Study. AB - In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline >=40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6+/-13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2+/-19.6 mL/min per 1.73 m(2), and clinic BP was 145+/ 18/80+/-11 mm Hg. Baseline ABP (daytime, 131+/-16/75+/-10 and nighttime, 122+/ 18/66+/-10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04-1.21 and 1.18, 1.08-1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005-0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29-3.59 and 1.71, 1.07-2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline. PMID- 26150435 TI - Chemerin Regulates Crosstalk Between Adipocytes and Vascular Cells Through Nox. AB - Adipocytes produce adipokines, including chemerin, a chemoattractant that mediates effects through its ChemR23 receptor. Chemerin has been linked to endothelial dysfunction and vascular injury in pathological conditions, such as obesity, diabetes mellitus, and hypertension. Molecular mechanisms underlying this are elusive. Here we assessed whether chemerin through redox-sensitive signaling influences molecular processes associated with vascular growth, apoptosis, and inflammation. Human microvascular endothelial cells and vascular smooth muscle cells were stimulated with chemerin (50 ng/mL). Chemerin increased generation of reactive oxygen species and phosphorylation of mitogen-activated protein kinases, effects that were inhibited by ML171, GKT137831 (Nox inhibitors), and N-acetylcysteine (reactive oxygen species scavenger). Chemerin increased mRNA expression of proinflammatory mediators in vascular cells and increased monocyte-to-endothelial cell attachment. In human vascular smooth muscle cells, chemerin induced phosphorylation of mitogen-activated protein kinases and stimulated proliferation (increased proliferating cell nuclear antigen expression [proliferation marker] and BrdU incorporation [proliferation assay]). Chemerin decreased phosphatidylinositol 3-kinase/protein kinase B activation and increased TUNEL-positive human vascular smooth muscle cells. In human microvascular endothelial cells, chemerin reduced endothelial nitric oxide synthase activity and nitric oxide production. Adipocyte-conditioned medium from obese/diabetic mice (db/db), which have elevated chemerin levels, increased reactive oxygen species generation in vascular smooth muscle cells, whereas adipocyte-conditioned medium from control mice had no effect. Chemerin actions were blocked by CCX 832, a ChemR23 inhibitor. Our data demonstrate that chemerin, through Nox activation and redox-sensitive mitogen-activated protein kinases signaling, exerts proapoptotic, proinflammatory, and proliferative effects in human vascular cells. These findings elucidate some molecular mechanisms through chemerin, which is increased in obesity, whereby adipocytes may influence vascular function. We identify chemerin as a novel vasoactive adipokine, which may be important in obesity-related vascular injury. PMID- 26150436 TI - Intradialysis Hypertension in End-Stage Renal Disease Patients: Clinical Epidemiology, Pathogenesis, and Treatment. PMID- 26150437 TI - Amino-Terminal Pro-B-Type Natriuretic Peptide Improves Discrimination for Incident Atherosclerotic Cardiovascular Disease Beyond Ambulatory Blood Pressure in Elderly Men. AB - Improvement of risk prediction for atherosclerotic cardiovascular disease (ASCVD) is needed. Both ambulatory blood pressure (ABP) and biomarkers amino-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein and cystatin C improve risk prediction but they have not been evaluated in relation to each other. We analyzed whether NT-proBNP, high-sensitivity C-reactive protein, or cystatin C improved risk prediction beyond traditional ASCVD risk factors combined with 24-hour systolic BP (SBP). Secondary aim was to evaluate whether ABP improved risk prediction when compared with models with the biomarkers. We followed up 907 70-year-old men, free of baseline disease, for incident ASCVD defined as fatal or nonfatal myocardial infarction or fatal or nonfatal stroke for a median of 10 years. Cox regression was used to estimate the association between variables in the models and incident ASCVD. Biomarkers were added to a model containing both traditional risk factors and ABP and the models were compared on C-statistics and net reclassification improvement. Twenty-four hour SBP improved discrimination for incident ASCVD when compared with office SBP in a traditional risk factor model (area under the receiver-operating characteristic curve, +2.4%). NT-proBNP further improved reclassification (+18.7% 19.9%; P<0.01) when added to ABP models, whereas high-sensitivity C-reactive protein and cystatin C did not. Twenty-four hour SBP significantly improved net reclassification when added to a traditional risk factor model that included NT proBNP. The combination of 24-hour SBP and NT-proBNP improved discrimination and net reclassification for incident ASCVD when compared with office SBP in elderly men. NT-proBNP, but not high-sensitivity C-reactive protein or cystatin C, improved risk prediction and discrimination when added to a model that included ABP. PMID- 26150438 TI - Implications of the Eighth Joint National Committee Guidelines for the Management of High Blood Pressure for Aging Adults: Atherosclerosis Risk in Communities Study. AB - The recent 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Eight Joint National Committee Panel may significantly affect the aging US population. We performed a cross-sectional analysis of black and white participants in Atherosclerosis Risk in Communities who participated in the fifth study visit (2011-2013). Sitting blood pressure was calculated from the average of 3 successive readings taken after a 5-minute rest. Currently, prescribed antihypertensive medications were recorded by reviewing medication containers brought to the visit. Blood pressure control was defined using both the Seventh and Eighth Joint National Committee thresholds. Of 6088 participants (mean age, 75.6 [range, 66-90] years, 58.4% women; 23.2% black), 54.9% had either diabetes mellitus or chronic kidney disease. The prevalence of hypertension according to Seventh Joint National Committee thresholds was 81.9%, and 62.8% of the entire sample were at blood pressure goal. Using the Eighth Joint National Committee thresholds, 79.4% were at blood pressure goal (16.6% were reclassified as at-goal). Reclassification was higher for individuals with diabetes mellitus or chronic kidney disease (20.6%) when compared with individuals without either condition (11.6%). The use of antihypertensive medications in our cohort was high, with 75.0% prescribed at least 1 antihypertensive medication and 46.7% on >=2 antihypertensive agents. In conclusion, in a US cohort of aging white and black individuals, ~1 in 6 individuals were reclassified as having blood pressure at goal by Eighth Joint National Committee guidelines. Despite these less aggressive goals, >20% remain uncontrolled by the new criteria. PMID- 26150439 TI - Salt Sensitivity in Response to Renal Injury Requires Renal Angiotensin Converting Enzyme. AB - Recent evidence indicates that salt-sensitive hypertension can result from a subclinical injury that impairs the kidneys' capacity to properly respond to a high-salt diet. However, how this occurs is not well understood. Here, we showed that although previously salt-resistant wild-type mice became salt sensitive after the induction of renal injury with the nitric oxide synthase inhibitor Nomega-nitro-l-arginine methyl ester hydrochloride; mice lacking renal angiotensin-converting enzyme, exposed to the same insult, did not become hypertensive when faced with a sodium load. This is because the activity of renal angiotensin-converting enzyme plays a critical role in (1) augmenting the local pool of angiotensin II and (2) the establishment of the antinatriuretic state via modulation of glomerular filtration rate and sodium tubular transport. Thus, this study demonstrates that the presence of renal angiotensin-converting enzyme plays a pivotal role in the development of salt sensitivity in response to renal injury. PMID- 26150440 TI - Final Results of a Prospective Evaluation of the Predictive Value of Interim Positron Emission Tomography in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP-14 (SAKK 38/07). AB - PURPOSE: Our main objective was to prospectively determine the prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 14 days (R-CHOP-14) under standardized treatment and PET evaluation criteria. PATIENTS AND METHODS: Patients with any stage of diffuse large B-cell lymphoma were treated with six cycles of R-CHOP-14 followed by two cycles of rituximab. PET/CT examinations were performed at baseline, after two cycles (and after four cycles if the patient was PET-positive after two cycles), and at the end of treatment. PET/CT examinations were evaluated locally and by central review. The primary end point was event-free survival at 2 years (2-year EFS). RESULTS: Median age of the 138 evaluable patients was 58.5 years with a WHO performance status of 0, 1, or 2 in 56%, 36%, or 8% of the patients, respectively. By local assessment, 83 PET/CT scans (60%) were reported as positive and 55 (40%) as negative after two cycles of R-CHOP-14. Two-year EFS was significantly shorter for PET-positive compared with PET negative patients (48% v 74%; P = .004). Overall survival at 2 years was not significantly different, with 88% for PET-positive versus 91% for PET-negative patients (P = .46). By using central review and the Deauville criteria, 2-year EFS was 41% versus 76% (P < .001) for patients who had interim PET/CT scans after two cycles of R-CHOP-14 and 24% versus 72% (P < .001) for patients who had PET/CT scans at the end of treatment. CONCLUSION: Our results confirmed that an interim PET/CT scan has limited prognostic value in patients with diffuse large B-cell lymphoma homogeneously treated with six cycles of R-CHOP-14 in a large prospective trial. At this point, interim PET/CT scanning is not ready for clinical use to guide treatment decisions in individual patients. PMID- 26150441 TI - Psychosocial and Neurocognitive Outcomes in Adult Survivors of Adolescent and Early Young Adult Cancer: A Report From the Childhood Cancer Survivor Study. AB - PURPOSE: To characterize psychological and neurocognitive function in long-term cancer survivors diagnosed during adolescence and early young adulthood (AeYA). METHODS: Six thousand one hundred ninety-two survivors and 390 siblings in the Childhood Cancer Survivor Study completed the Brief Symptom Inventory-18 and a Neurocognitive Questionnaire. Treatment and demographic predictors were examined, and associations with social attainment (employment, education, and living independently) were evaluated. Logistic regression models were used to compute odds ratios (ORs) and corresponding 95% CIs. RESULTS: Among survivors, 2,589 were diagnosed when AeYA (11 to 21 years old). Adjusted for current age and sex, these survivors, compared with siblings, self-reported higher rates of depression (11.7% v 8.0%, respectively; OR, 1.55; 95% CI, 1.04 to 2.30) and anxiety (7.4% v 4.4%, respectively; OR, 2.00; 95% CI, 1.17 to 3.43) and more problems with task efficiency (17.2% v 10.8%, respectively; OR, 1.72; 95% CI, 1.21 to 2.43), emotional regulation (19.1% v 14.1%, respectively; OR, 1.74; 95% CI, 1.26 to 2.40), and memory (25.9% v 19.0%, respectively; OR, 1.44; 95% CI, 1.09 to 1.89). Few differences were noted between survivors diagnosed with leukemia or CNS tumor before 11 years old versus during later adolescence, although those diagnosed with lymphoma or sarcoma during AeYA were at reduced risk for self-reported psychosocial and neurocognitive problems. Unemployment was associated with self reports of impaired task efficiency (OR, 2.93; 95% CI, 2.28 to 3.77), somatization (OR, 2.29; 95% CI, 1.77 to 2.98), and depression (OR, 1.94; 95% CI, 1.43 to 2.63). CONCLUSION: We demonstrated that risk for poor functional outcome is not limited to survivors' diagnoses in early childhood. AeYA is a critical period of development, and cancer during this period can impact neurocognitive and emotional function and disrupt vocational attainment. PMID- 26150442 TI - Postoperative Radiation Therapy for Endometrial Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline. AB - PURPOSE: To provide guidance on the role of adjuvant radiation therapy in the treatment of endometrial cancer. METHODS: "The Role of Postoperative Radiation Therapy for Endometrial Cancer: An ASTRO Evidence-Based Guideline" by Klopp et al, published in 2014 in Practical Radiation Oncology, was reviewed for developmental rigor by methodologists. The American Society for Radiation Oncology (ASTRO) guideline content and recommendations were further reviewed by the American Society of Clinical Oncology (ASCO) Endorsement Panel. RESULTS: The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the ASTRO guideline with several qualifying statements. RECOMMENDATIONS: Surveillance without adjuvant radiation therapy is a reasonable option for women without residual disease in the hysterectomy specimen and for women with grade 1 or 2 cancer and < 50% myometrial invasion, especially when no other high-risk features are present. For women with grade 1 or 2 cancer and >= 50% myometrial invasion or grade 3 cancer and < 50% myometrial invasion, vaginal brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence and is preferred. Patients with grade 3 cancer and >= 50% myometrial invasion or cervical stroma invasion may benefit from pelvic radiation to prevent pelvic recurrence. For women with high-risk early-stage disease and advanced disease, the ASCO Endorsement Panel added qualifying statements to the ASTRO recommendations to provide stronger statements in favor of chemotherapy (with or without radiation therapy). PMID- 26150443 TI - Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma. AB - PURPOSE: Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. PATIENTS AND METHODS: Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. RESULTS: ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). CONCLUSION: The addition of cell adhesion-linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis. PMID- 26150444 TI - Multinational Randomized Phase III Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After Concurrent Chemoradiation in Inoperable Stage III Non-Small-Cell Lung Cancer: KCSG-LU05-04. AB - PURPOSE: To determine the efficacy of consolidation chemotherapy (CC) with docetaxel and cisplatin (DP) after concurrent chemoradiotherapy (CCRT) with the same agents in locally advanced non-small-cell lung cancer (LA-NSCLC). PATIENT AND METHODS: Patients were randomly assigned to either CCRT alone (observation arm) or CCRT followed by CC (consolidation arm). CCRT with docetaxel (20 mg/m(2)) and cisplatin (20 mg/m(2)) was administered every week for 6 weeks with a total dose of 66 Gy of thoracic radiotherapy in 33 fractions. In the consolidation arm, patients were further treated with three cycles of DP (35 mg/m(2) each on days 1 and 8, every 3 weeks). The primary end point was 40% improvement in progression free survival (PFS) compared with observation. RESULTS: From October 2005 to April 2011, 437 patients were randomly assigned. Seventeen patients did not start CCRT as a result of consent withdrawal or ineligibility reasons after random assignment, leaving 420 patients for this analysis (n = 211 for observation; n = 209 for consolidation). Patient characteristics were similar in both arms. In the consolidation arm, 143 patients (68%) received CC, of whom 88 (62%) completed three planned cycles. The median PFS was 8.1 months in the observation arm and 9.1 months in the consolidation arm (hazard ratio, 0.91; 95% CI, 0.73 to 1.12; P = .36). Median overall survival times were 20.6 and 21.8 months in the observation and consolidation arms, respectively (HR, 0.91; 95% CI, 0.72 to 1.25; P = .44). CONCLUSION: CC with DP after CCRT with weekly DP in LA-NSCLC failed to further prolong PFS. CCRT alone should remain the standard of care. PMID- 26150445 TI - Race and Insurance Differences in the Receipt of Adjuvant Chemotherapy Among Patients With Stage III Colon Cancer. AB - PURPOSE: Although the incidence and mortality of colon cancer in the United States has declined over the past two decades, blacks have worse outcomes than whites. Variations in treatment may contribute to mortality differentials. METHODS: Patients diagnosed with stage III colon cancer were randomly sampled from the SEER program from the years 1990, 1991, 1995, 2000, 2005, and 2010. Patients were categorized as non-Hispanic white (n = 835) or black (n = 384). Treatment data were obtained from a review of the medical records, and these data were verified through contact with the original treating physicians. Log-binomial regression models were used to estimate the association between race and receipt of adjuvant chemotherapy. Effect modification by insurance was assessed with use of single referent models. RESULTS: Receipt of adjuvant chemotherapy among both white and black patients increased from the period encompassing the years 1990 and 1991 (white, 58%; black, 45%) to the year 2005 (white, 72%; black, 71%) and then decreased in the year 2010 (white, 66%; black, 57%). There were marked racial disparities in the time period of 1990 to 1991 and again in 2010, with black patients less likely to receive adjuvant chemotherapy as compared with white patients (risk ratio [RR], .82; 95% CI, .72 to .93). For black patients, receipt of adjuvant chemotherapy did not differ across insurance categories (RR for private insurance, .80; 95% CI, .69 to .93; RR for Medicare, .84; 95% CI, .69 to 1.02; and RR for Medicaid, .84; 95% CI, .69 to 1.02), although a larger proportion had Medicaid in all years of the study as compared with white patients. CONCLUSION: The chemotherapy differential narrowed after the time period of 1990 to 1991, but our findings suggest that the disparity reemerged in 2010. Recent decreases in chemotherapy use may be due, in part, to the economic downturn and an increase in Medicaid coverage. PMID- 26150446 TI - Bias Correction Methods Explain Much of the Variation Seen in Breast Cancer Risks of BRCA1/2 Mutation Carriers. AB - PURPOSE: Recommendations for treating patients who carry a BRCA1/2 gene are mainly based on cumulative lifetime risks (CLTRs) of breast cancer determined from retrospective cohorts. These risks vary widely (27% to 88%), and it is important to understand why. We analyzed the effects of methods of risk estimation and bias correction and of population factors on CLTRs in this retrospective clinical cohort of BRCA1/2 carriers. PATIENTS AND METHODS: The following methods to estimate the breast cancer risk of BRCA1/2 carriers were identified from the literature: Kaplan-Meier, frailty, and modified segregation analyses with bias correction consisting of including or excluding index patients combined with including or excluding first-degree relatives (FDRs) or different conditional likelihoods. These were applied to clinical data of BRCA1/2 families derived from our family cancer clinic for whom a simulation was also performed to evaluate the methods. CLTRs and 95% CIs were estimated and compared with the reference CLTRs. RESULTS: CLTRs ranged from 35% to 83% for BRCA1 and 41% to 86% for BRCA2 carriers at age 70 years width of 95% CIs: 10% to 35% and 13% to 46%, respectively). Relative bias varied from -38% to +16%. Bias correction with inclusion of index patients and untested FDRs gave the smallest bias: +2% (SD, 2%) in BRCA1 and +0.9% (SD, 3.6%) in BRCA2. CONCLUSION: Much of the variation in breast cancer CLTRs in retrospective clinical BRCA1/2 cohorts is due to the bias correction method, whereas a smaller part is due to population differences. Kaplan-Meier analyses with bias correction that includes index patients and a proportion of untested FDRs provide suitable CLTRs for carriers counseled in the clinic. PMID- 26150447 TI - Detection of Low-Level Cardinium and Wolbachia Infections in Culicoides. AB - Bacterial endosymbionts have been identified as potentially useful biological control agents for a range of invertebrate vectors of disease. Previous studies of Culicoides (Diptera: Ceratopogonidae) species using conventional PCR assays have provided evidence of Wolbachia (1/33) and Cardinium (8/33) infections. Here, we screened 20 species of Culicoides for Wolbachia and Cardinium, utilizing a combination of conventional PCR and more sensitive quantitative PCR (qPCR) assays. Low levels of Cardinium DNA were detected in females of all but one of the Culicoides species screened, and low levels of Wolbachia were detected in females of 9 of the 20 Culicoides species. Sequence analysis based on partial 16S rRNA gene and gyrB sequences identified "Candidatus Cardinium hertigii" from group C, which has previously been identified in Culicoides from Japan, Israel, and the United Kingdom. Wolbachia strains detected in this study showed 98 to 99% sequence identity to Wolbachia previously detected from Culicoides based on the 16S rRNA gene, whereas a strain with a novel wsp sequence was identified in Culicoides narrabeenensis. Cardinium isolates grouped to geographical regions independent of the host Culicoides species, suggesting possible geographical barriers to Cardinium movement. Screening also identified Asaia bacteria in Culicoides. These findings point to a diversity of low-level endosymbiont infections in Culicoides, providing candidates for further characterization and highlighting the widespread occurrence of these endosymbionts in this insect group. PMID- 26150448 TI - Arsenophonus and Sodalis Symbionts in Louse Flies: an Analogy to the Wigglesworthia and Sodalis System in Tsetse Flies. AB - Symbiosis between insects and bacteria result in a variety of arrangements, genomic modifications, and metabolic interconnections. Here, we present genomic, phylogenetic, and morphological characteristics of a symbiotic system associated with Melophagus ovinus, a member of the blood-feeding family Hippoboscidae. The system comprises four unrelated bacteria representing different stages in symbiosis evolution, from typical obligate mutualists inhabiting bacteriomes to freely associated commensals and parasites. Interestingly, the whole system provides a remarkable analogy to the association between Glossina and its symbiotic bacteria. In both, the symbiotic systems are composed of an obligate symbiont and two facultative intracellular associates, Sodalis and Wolbachia. In addition, extracellular Bartonella resides in the gut of Melophagus. However, the phylogenetic origins of the two obligate mutualist symbionts differ. In Glossina, the mutualistic Wigglesworthia appears to be a relatively isolated symbiotic lineage, whereas in Melophagus, the obligate symbiont originated within the widely distributed Arsenophonus cluster. Although phylogenetically distant, the two obligate symbionts display several remarkably similar traits (e.g., transmission via the host's "milk glands" or similar pattern of genome reduction). To obtain better insight into the biology and possible role of the M. ovinus obligate symbiont, "Candidatus Arsenophonus melophagi," we performed several comparisons of its gene content based on assignments of the Cluster of Orthologous Genes (COG). Using this criterion, we show that within a set of 44 primary and secondary symbionts, "Ca. Arsenophonus melophagi" is most similar to Wigglesworthia. On the other hand, these two bacteria also display interesting differences, such as absence of flagellar genes in Arsenophonus and their presence in Wigglesworthia. This finding implies that a flagellum is not essential for bacterial transmission via milk glands. PMID- 26150449 TI - Variation in the Microbiota of Ixodes Ticks with Regard to Geography, Species, and Sex. AB - Ixodes scapularis is the principal vector of Lyme disease on the East Coast and in the upper Midwest regions of the United States, yet the tick is also present in the Southeast, where Lyme disease is absent or rare. A closely related species, I. affinis, also carries the pathogen in the South but does not seem to transmit it to humans. In order to better understand the geographic diversity of the tick, we analyzed the microbiota of 104 adult I. scapularis and 13 adult I. affinis ticks captured in 19 locations in South Carolina, North Carolina, Virginia, Connecticut, and New York. Initially, ticks from 4 sites were analyzed by 454 pyrosequencing. Subsequently, ticks from these sites plus 15 others were analyzed by sequencing with an Illumina MiSeq machine. By both analyses, the microbiomes of female ticks were significantly less diverse than those of male ticks. The dissimilarity between tick microbiomes increased with distance between sites, and the state in which a tick was collected could be inferred from its microbiota. The genus Rickettsia was prominent in all locations. Borrelia was also present in most locations and was present at especially high levels in one site in western Virginia. In contrast, members of the family Enterobacteriaceae were very common in North Carolina I. scapularis ticks but uncommon in I. scapularis ticks from other sites and in North Carolina I. affinis ticks. These data suggest substantial variations in the Ixodes microbiota in association with geography, species, and sex. PMID- 26150450 TI - Dynamics of Photosynthesis in a Glycogen-Deficient glgC Mutant of Synechococcus sp. Strain PCC 7002. AB - Cyanobacterial glycogen-deficient mutants display impaired degradation of light harvesting phycobilisomes under nitrogen-limiting growth conditions and secrete a suite of organic acids as a putative reductant-spilling mechanism. This genetic background, therefore, represents an important platform to better understand the complex relationships between light harvesting, photosynthetic electron transport, carbon fixation, and carbon/nitrogen metabolisms. In this study, we conducted a comprehensive analysis of the dynamics of photosynthesis as a function of reductant sink manipulation in a glycogen-deficient glgC mutant of Synechococcus sp. strain PCC 7002. The glgC mutant showed increased susceptibility to photoinhibition during the initial phase of nitrogen deprivation. However, after extended periods of nitrogen deprivation, glgC mutant cells maintained higher levels of photosynthetic activity than the wild type, supporting continuous organic acid secretion in the absence of biomass accumulation. In contrast to the wild type, the glgC mutant maintained efficient energy transfer from phycobilisomes to photosystem II (PSII) reaction centers, had an elevated PSII/PSI ratio as a result of reduced PSII degradation, and retained a nitrogen-replete-type ultrastructure, including an extensive thylakoid membrane network, after prolonged nitrogen deprivation. Together, these results suggest that multiple global signals for nitrogen deprivation are not activated in the glgC mutant, allowing the maintenance of active photosynthetic complexes under conditions where photosynthesis would normally be abolished. PMID- 26150451 TI - Diversity, Structures, and Collagen-Degrading Mechanisms of Bacterial Collagenolytic Proteases. AB - Bacterial collagenolytic proteases are important because of their essential role in global collagen degradation and because of their virulence in some human bacterial infections. Bacterial collagenolytic proteases include some metalloproteases of the M9 family from Clostridium or Vibrio strains, some serine proteases distributed in the S1, S8, and S53 families, and members of the U32 family. In recent years, there has been remarkable progress in discovering new bacterial collagenolytic proteases and in investigating the collagen-degrading mechanisms of bacterial collagenolytic proteases. This review provides comprehensive insight into bacterial collagenolytic proteases, especially focusing on the structures and collagen-degrading mechanisms of representative bacterial collagenolytic proteases in each family. The roles of bacterial collagenolytic proteases in human diseases and global nitrogen cycling, together with the biotechnological and medical applications for these proteases, are also briefly discussed. PMID- 26150452 TI - Public Health Risks of Multiple-Drug-Resistant Enterococcus spp. in Southeast Asia. AB - Enterococci rank as one of the leading causes of nosocomial infections, such as urinary tract infections, surgical wound infections, and endocarditis, in humans. These infections can be hard to treat because of the rising incidence of antibiotic resistance. Enterococci inhabiting nonhuman reservoirs appear to play a critical role in the acquisition and dissemination of antibiotic resistance determinants. The spread of antibiotic resistance has become a major concern in both human and veterinary medicine, especially in Southeast Asia, where many developing countries have poor legislation and regulations to control the supply and excessive use of antimicrobials. This review addresses the occurrence of antibiotic-resistant enterococci in Association of Southeast Asian Nations countries and proposes infection control measures that should be applied to limit the spread of multiple-drug-resistant enterococci. PMID- 26150453 TI - Uterine Microbiota Progression from Calving until Establishment of Metritis in Dairy Cows. AB - The objective of this study was to evaluate the progression of the uterine microbiota from calving until establishment of metritis. Uterine swabs (n = 72) collected at 0, 2, and 6 +/- 2 days postpartum (dpp) from 12 metritic and 12 healthy cows were used for metagenomic sequencing of the 16S rRNA gene on the Illumina MiSeq platform. A heat map showed that uterine microbiota was established at calving. The microbiota changed rapidly from 0 to 6 +/- 2 dpp, with a decrease in the abundance of Proteobacteria and an increase in the abundance of Bacteroidetes and Fusobacteria, which were dominant in metritic cows. Uterine microbiota composition was shared; however, metritic and healthy cows could be discriminated using relative abundance of bacterial genera at 0, 2, and 6 +/- 2 dpp. Bacteroides was the main genus associated with metritis because it was the only genus that showed significantly greater abundance in cows with metritis. As the abundance of Bacteroides organisms increased, the uterine discharge score, a measure of uterine health, worsened. Fusobacterium was also an important genus associated with metritis because Fusobacterium abundance increased as Bacteroides abundance increased and the uterine discharge score worsened as the abundance increased. The correlation with uterine discharge score and the correlation with Bacteroides or Fusobacterium showed that other bacteria, such as Helcoccocus, Filifactor, and Porphyromonas, were also associated with metritis. There were also bacteria associated with uterine health, such as "Candidatus Blochmannia," Escherichia, Sneathia, and Pedobacter. PMID- 26150454 TI - Chromosomal Copy Number Variation in Saccharomyces pastorianus Is Evidence for Extensive Genome Dynamics in Industrial Lager Brewing Strains. AB - Lager brewing strains of Saccharomyces pastorianus are natural interspecific hybrids originating from the spontaneous hybridization of Saccharomyces cerevisiae and Saccharomyces eubayanus. Over the past 500 years, S. pastorianus has been domesticated to become one of the most important industrial microorganisms. Production of lager-type beers requires a set of essential phenotypes, including the ability to ferment maltose and maltotriose at low temperature, the production of flavors and aromas, and the ability to flocculate. Understanding of the molecular basis of complex brewing-related phenotypic traits is a prerequisite for rational strain improvement. While genome sequences have been reported, the variability and dynamics of S. pastorianus genomes have not been investigated in detail. Here, using deep sequencing and chromosome copy number analysis, we showed that S. pastorianus strain CBS1483 exhibited extensive aneuploidy. This was confirmed by quantitative PCR and by flow cytometry. As a direct consequence of this aneuploidy, a massive number of sequence variants was identified, leading to at least 1,800 additional protein variants in S. pastorianus CBS1483. Analysis of eight additional S. pastorianus strains revealed that the previously defined group I strains showed comparable karyotypes, while group II strains showed large interstrain karyotypic variability. Comparison of three strains with nearly identical genome sequences revealed substantial chromosome copy number variation, which may contribute to strain-specific phenotypic traits. The observed variability of lager yeast genomes demonstrates that systematic linking of genotype to phenotype requires a three-dimensional genome analysis encompassing physical chromosomal structures, the copy number of individual chromosomes or chromosomal regions, and the allelic variation of copies of individual genes. PMID- 26150455 TI - Reconstitution of the In Vitro Activity of the Cyclosporine-Specific P450 Hydroxylase from Sebekia benihana and Development of a Heterologous Whole-Cell Biotransformation System. AB - The cytochrome P450 enzyme CYP-sb21 from Sebekia benihana is capable of catalyzing the site-specific hydroxylation of the immunosuppressant cyclosporine (CsA), leading to the single product gamma-hydroxy-N-methyl-l-Leu4-CsA (CsA-4 OH). Unlike authentic CsA, this hydroxylated CsA shows significantly reduced immunosuppressive activity while it retains a side effect of CsA, the hair growth stimulation effect. Although CYP-sb21 was previously identified to be responsible for CsA-specific hydroxylation in vivo, the in vitro activity of CYP-sb21 has yet to be established for a deeper understanding of this P450 enzyme and further reaction optimization. In this study, we reconstituted the in vitro activity of CYP-sb21 by using surrogate redox partner proteins of bacterial and cyanobacterial origins. The highest CsA site-specific hydroxylation activity by CYP-sb21 was observed when it was partnered with the cyanobacterial redox system composed of seFdx and seFdR from Synechococcus elongatus PCC 7942. The best bioconversion yields were obtained in the presence of 10% methanol as a cosolvent and an NADPH regeneration system. A heterologous whole-cell biocatalyst using Escherichia coli was also constructed, and the permeability problem was solved by using N-cetyl-N,N,N-trimethylammonium bromide (CTAB). This work provides a useful example for reconstituting a hybrid P450 system and developing it into a promising biocatalyst for industrial application. PMID- 26150456 TI - Development of a Recombinant Escherichia coli Strain for Overproduction of the Plant Pigment Anthocyanin. AB - Anthocyanins are water-soluble colored pigments found in terrestrial plants and are responsible for the red, blue, and purple coloration of many flowers and fruits. In addition to the plethora of health benefits associated with anthocyanins (cardioprotective, anti-inflammatory, antioxidant, and antiaging properties), these compounds have attracted widespread attention due to their promising potential as natural food colorants. Previously, we reported the biotransformation of anthocyanin, specifically cyanidin 3-O-glucoside (C3G), from the substrate (+)-catechin in Escherichia coli. In the present work, we set out to systematically improve C3G titers by enhancing substrate and precursor availability, balancing gene expression level, and optimizing cultivation and induction parameters. We first identified E. coli transporter proteins that are responsible for the uptake of catechin and secretion of C3G. We then improved the expression of the heterologous pathway enzymes anthocyanidin synthase (ANS) and 3 O-glycosyltransferase (3GT) using a bicistronic expression cassette. Next, we augmented the intracellular availability of the critical precursor UDP-glucose, which has been known as the rate-limiting precursor to produce glucoside compounds. Further optimization of culture and induction conditions led to a final titer of 350 mg/liter of C3G. We also developed a convenient colorimetric assay for easy screening of C3G overproducers. The work reported here constitutes a promising foundation to develop a cost-effective process for large-scale production of plant-derived anthocyanin from recombinant microorganisms. PMID- 26150457 TI - Breeding Strategy To Generate Robust Yeast Starter Cultures for Cocoa Pulp Fermentations. AB - Cocoa pulp fermentation is a spontaneous process during which the natural microbiota present at cocoa farms is allowed to ferment the pulp surrounding cocoa beans. Because such spontaneous fermentations are inconsistent and contribute to product variability, there is growing interest in a microbial starter culture that could be used to inoculate cocoa pulp fermentations. Previous studies have revealed that many different fungi are recovered from different batches of spontaneous cocoa pulp fermentations, whereas the variation in the prokaryotic microbiome is much more limited. In this study, therefore, we aimed to develop a suitable yeast starter culture that is able to outcompete wild contaminants and consistently produce high-quality chocolate. Starting from specifically selected Saccharomyces cerevisiae strains, we developed robust hybrids with characteristics that allow them to efficiently ferment cocoa pulp, including improved temperature tolerance and fermentation capacity. We conducted several laboratory and field trials to show that these new hybrids often outperform their parental strains and are able to dominate spontaneous pilot scale fermentations, which results in much more consistent microbial profiles. Moreover, analysis of the resulting chocolate showed that some of the cocoa batches that were fermented with specific starter cultures yielded superior chocolate. Taken together, these results describe the development of robust yeast starter cultures for cocoa pulp fermentations that can contribute to improving the consistency and quality of commercial chocolate production. PMID- 26150459 TI - Differences in Physical and Biochemical Properties of Thermus scotoductus SA-01 Cultured with Dielectric or Convection Heating. AB - A thermophile, Thermus scotoductus SA-01, was cultured within a constant temperature (65 degrees C) microwave (MW) digester to determine if MW-specific effects influenced the growth and physiology of the organism. As a control, T. scotoductus cells were also cultured using convection heating at the same temperature as the MW studies. Cell growth was analyzed by optical density (OD) measurements, and cell morphologies were characterized using electron microscopy imaging (scanning electron microscopy [SEM] and transmission electron microscopy [TEM]), dynamic light scattering (DLS), and atomic force microscopy (AFM). Biophysical properties (i.e., turgor pressure) were also calculated with AFM, and biochemical compositions (i.e., proteins, nucleic acids, fatty acids) were analyzed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the fatty acid methyl esters extracted from cell membranes. Here we report successful cultivation of a thermophile with only dielectric heating. Under the MW conditions for growth, cell walls remained intact and there were no indications of membrane damage or cell leakage. Results from these studies also demonstrated that T. scotoductus cells grown with MW heating exhibited accelerated growth rates in addition to altered cell morphologies and biochemical compositions compared with oven-grown cells. PMID- 26150458 TI - Microbial Toluene Removal in Hypoxic Model Constructed Wetlands Occurs Predominantly via the Ring Monooxygenation Pathway. AB - In the present study, microbial toluene degradation in controlled constructed wetland model systems, planted fixed-bed reactors (PFRs), was queried with DNA based methods in combination with stable isotope fractionation analysis and characterization of toluene-degrading microbial isolates. Two PFR replicates were operated with toluene as the sole external carbon and electron source for 2 years. The bulk redox conditions in these systems were hypoxic to anoxic. The autochthonous bacterial communities, as analyzed by Illumina sequencing of 16S rRNA gene amplicons, were mainly comprised of the families Xanthomonadaceae, Comamonadaceae, and Burkholderiaceae, plus Rhodospirillaceae in one of the PFR replicates. DNA microarray analyses of the catabolic potentials for aromatic compound degradation suggested the presence of the ring monooxygenation pathway in both systems, as well as the anaerobic toluene pathway in the PFR replicate with a high abundance of Rhodospirillaceae. The presence of catabolic genes encoding the ring monooxygenation pathway was verified by quantitative PCR analysis, utilizing the obtained toluene-degrading isolates as references. Stable isotope fractionation analysis showed low-level of carbon fractionation and only minimal hydrogen fractionation in both PFRs, which matches the fractionation signatures of monooxygenation and dioxygenation. In combination with the results of the DNA-based analyses, this suggests that toluene degradation occurs predominantly via ring monooxygenation in the PFRs. PMID- 26150460 TI - The Host as the Driver of the Microbiota in the Gut and External Environment of Drosophila melanogaster. AB - Most associations between animals and their gut microbiota are dynamic, involving sustained transfer of food-associated microbial cells into the gut and shedding of microorganisms into the external environment with feces, but the interacting effects of host and microbial factors on the composition of the internal and external microbial communities are poorly understood. This study on laboratory cultures of the fruit fly Drosophila melanogaster reared in continuous contact with their food revealed time-dependent changes of the microbial communities in the food that were strongly influenced by the presence and abundance of Drosophila. When germfree Drosophila eggs were aseptically added to nonsterile food, the microbiota in the food and flies converged to a composition dramatically different from that in fly-free food, showing that Drosophila has microbiota-independent effects on the food microbiota. The microbiota in both the flies that developed from unmanipulated eggs (bearing microorganisms) and the associated food was dominated by the bacteria most abundant on the eggs, demonstrating effective vertical transmission via surface contamination of eggs. Food coinoculated with a four-species defined bacterial community of Acetobacter and Lactobacillus species revealed the progressive elimination of Lactobacillus from the food bearing few or no Drosophila, indicating the presence of antagonistic interactions between Acetobacter and Lactobacillus. Drosophila at high densities ameliorated the Acetobacter/Lactobacillus antagonism, enabling Lactobacillus to persist. This study with Drosophila demonstrates how animals can have major, coordinated effects on the composition of microbial communities in the gut and immediate environment. PMID- 26150461 TI - NADP+-Preferring D-Lactate Dehydrogenase from Sporolactobacillus inulinus. AB - Hydroxy acid dehydrogenases, including l- and d-lactate dehydrogenases (L-LDH and D-LDH), are responsible for the stereospecific conversion of 2-keto acids to 2 hydroxyacids and extensively used in a wide range of biotechnological applications. A common feature of LDHs is their high specificity for NAD(+) as a cofactor. An LDH that could effectively use NADPH as a coenzyme could be an alternative enzymatic system for regeneration of the oxidized, phosphorylated cofactor. In this study, a d-lactate dehydrogenase from a Sporolactobacillus inulinus strain was found to use both NADH and NADPH with high efficiencies and with a preference for NADPH as its coenzyme, which is different from the coenzyme utilization of all previously reported LDHs. The biochemical properties of the D LDH enzyme were determined by X-ray crystal structural characterization and in vivo and in vitro enzymatic activity analyses. The residue Asn(174) was demonstrated to be critical for NADPH utilization. Characterization of the biochemical properties of this enzyme will contribute to understanding of the catalytic mechanism and provide referential information for shifting the coenzyme utilization specificity of 2-hydroxyacid dehydrogenases. PMID- 26150462 TI - Novel Strategies for Genomic Manipulation of Trichoderma reesei with the Purpose of Strain Engineering. AB - The state-of-the-art procedure for gene insertions into Trichoderma reesei is a cotransformation of two plasmids, one bearing the gene of interest and the other a marker gene. This procedure yields up to 80% transformation efficiency, but both the number of integrated copies and the loci of insertion are unpredictable. This can lead to tremendous pleiotropic effects. This study describes the development of a novel transformation system for site-directed gene insertion based on auxotrophic markers. For this purpose, we tested the applicability of the genes asl1 (encoding an enzyme of the l-arginine biosynthesis pathway), the hah1 (encoding an enzyme of the l-lysine biosynthesis pathway), and the pyr4 (encoding an enzyme of the uridine biosynthesis pathway). The developed transformation system yields strains with an additional gene at a defined locus that are prototrophic and ostensibly isogenic compared to their parental strain. A positive transformation rate of 100% was achieved due to the developed split marker system. Additionally, a double-auxotrophic strain that allows multiple genomic manipulations was constructed, which facilitates metabolic engineering purposes in T. reesei. By employing goxA of Aspergillus niger as a reporter system, the influence on the expression of an inserted gene caused by the orientation of the insertion and the transformation strategy used could be demonstrated. Both are important aspects to be considered during strain engineering. PMID- 26150463 TI - Effects of Trichothecene Production on the Plant Defense Response and Fungal Physiology: Overexpression of the Trichoderma arundinaceum tri4 Gene in T. harzianum. AB - Trichothecenes are fungal sesquiterpenoid compounds, the majority of which have phytotoxic activity. They contaminate food and feed stocks, resulting in potential harm to animals and human beings. Trichoderma brevicompactum and T. arundinaceum produce trichodermin and harzianum A (HA), respectively, two trichothecenes that show different bioactive properties. Both compounds have remarkable antibiotic and cytotoxic activities, but in addition, trichodermin is highly phytotoxic, while HA lacks this activity when analyzed in vivo. Analysis of Fusarium trichothecene intermediates led to the conclusion that most of them, with the exception of the hydrocarbon precursor trichodiene (TD), have a detectable phytotoxic activity which is not directly related to the structural complexity of the intermediate. In the present work, the HA intermediate 12,13 epoxytrichothec-9-ene (EPT) was produced by expression of the T. arundinaceum tri4 gene in a transgenic T. harzianum strain that already produces TD after transformation with the T. arundinaceum tri5 gene. Purified EPT did not show antifungal or phytotoxic activity, while purified HA showed both antifungal and phytotoxic activities. However, the use of the transgenic T. harzianum tri4 strain induced a downregulation of defense-related genes in tomato plants and also downregulated plant genes involved in fungal root colonization. The production of EPT by the transgenic tri4 strain raised levels of erg1 expression and reduced squalene accumulation while not affecting levels of ergosterol. Together, these results indicate the complex interactions among trichothecene intermediates, fungal antagonists, and host plants. PMID- 26150464 TI - Improving the Thermostability and Activity of a Thermophilic Subtilase by Incorporating Structural Elements of Its Psychrophilic Counterpart. AB - The incorporation of the structural elements of thermostable enzymes into their less stable counterparts is generally used to improve enzyme thermostability. However, the process of engineering enzymes with both high thermostability and high activity remains an important challenge. Here, we report that the thermostability and activity of a thermophilic subtilase were simultaneously improved by incorporating structural elements of a psychrophilic subtilase. There were 64 variable regions/residues (VRs) in the alignment of the thermophilic WF146 protease, mesophilic sphericase, and psychrophilic S41. The WF146 protease was subjected to systematic mutagenesis, in which each of its VRs was replaced with those from S41 and sphericase. After successive rounds of combination and screening, we constructed the variant PBL5X with eight amino acid residues from S41. The half-life of PBL5X at 85 degrees C (57.1 min) was approximately 9-fold longer than that of the wild-type (WT) WF146 protease (6.3 min). The substitutions also led to an increase in the apparent thermal denaturation midpoint temperature (Tm) of the enzyme by 5.5 degrees C, as determined by differential scanning calorimetry. Compared to the WT, PBL5X exhibited high caseinolytic activity (25 to 95 degrees C) and high values of Km and kcat (25 to 80 degrees C). Our study may provide a rational basis for developing highly stable and active enzymes, which are highly desired in industrial applications. PMID- 26150465 TI - Abundant Trimethylornithine Lipids and Specific Gene Sequences Are Indicative of Planctomycete Importance at the Oxic/Anoxic Interface in Sphagnum-Dominated Northern Wetlands. AB - Northern wetlands make up a substantial terrestrial carbon sink and are often dominated by decay-resistant Sphagnum mosses. Recent studies have shown that planctomycetes appear to be involved in degradation of Sphagnum-derived debris. Novel trimethylornithine (TMO) lipids have recently been characterized as abundant lipids in various Sphagnum wetland planctomycete isolates, but their occurrence in the environment has not yet been confirmed. We applied a combined intact polar lipid (IPL) and molecular analysis of peat cores collected from two northern wetlands (Saxnas Mosse [Sweden] and Obukhovskoye [Russia]) in order to investigate the preferred niche and abundance of TMO-producing planctomycetes. TMOs were present throughout the profiles of Sphagnum bogs, but their concentration peaked at the oxic/anoxic interface, which coincided with a maximum abundance of planctomycete-specific 16S rRNA gene sequences. The sequences detected at the oxic/anoxic interface were affiliated with the Isosphaera group, while sequences present in the anoxic peat layers were related to an uncultured planctomycete group. Pyrosequencing-based analysis identified Planctomycetes as the major bacterial group at the oxic/anoxic interface at the Obukhovskoye peat (54% of total 16S rRNA gene sequence reads), followed by Acidobacteria (19% reads), while in the Saxnas Mosse peat, Acidobacteria were dominant (46%), and Planctomycetes contributed to 6% of the total reads. The detection of abundant TMO lipids in planctomycetes isolated from peat bogs and the lack of TMO production by cultures of acidobacteria suggest that planctomycetes are the producers of TMOs in peat bogs. The higher accumulation of TMOs at the oxic/anoxic interface and the change in the planctomycete community with depth suggest that these IPLs could be synthesized as a response to changing redox conditions at the oxic/anoxic interface. PMID- 26150466 TI - Host and Environmental Factors Modulate the Exposure of Free-Ranging and Farmed Red Deer (Cervus elaphus) to Coxiella burnetii. AB - The control of multihost pathogens, such as Coxiella burnetii, should rely on accurate information about the roles played by the main hosts. We aimed to determine the involvement of the red deer (Cervus elaphus) in the ecology of C. burnetii. We predicted that red deer populations from broad geographic areas within a European context would be exposed to C. burnetii, and therefore, we hypothesized that a series of factors would modulate the exposure of red deer to C. burnetii. To test this hypothesis, we designed a retrospective survey of 47 Iberian red deer populations from which 1,751 serum samples and 489 spleen samples were collected. Sera were analyzed by enzyme-linked immunosorbent assays (ELISA) in order to estimate exposure to C. burnetii, and spleen samples were analyzed by PCR in order to estimate the prevalence of systemic infections. Thereafter, we gathered 23 variables-within environmental, host, and management factors-potentially modulating the risk of exposure of deer to C. burnetii, and we performed multivariate statistical analyses to identify the main risk factors. Twenty-three populations were seropositive (48.9%), and C. burnetii DNA in the spleen was detected in 50% of the populations analyzed. The statistical analyses reflect the complexity of C. burnetii ecology and suggest that although red deer may maintain the circulation of C. burnetii without third species, the most frequent scenario probably includes other wild and domestic host species. These findings, taken together with previous evidence of C. burnetii shedding by naturally infected red deer, point at this wild ungulate as a true reservoir for C. burnetii and an important node in the life cycle of C. burnetii, at least in the Iberian Peninsula. PMID- 26150467 TI - Seasonal Changes Drive Short-Term Selection for Fitness Traits in the Wheat Pathogen Zymoseptoria tritici. AB - In a cross-infection experiment, we investigated how seasonal changes can affect adaptation patterns in a Zymoseptoria tritici population. The fitness of isolates sampled on wheat leaves at the beginning and at the end of a field epidemic was assessed under environmental conditions (temperature and host stage) to which the local pathogen population was successively exposed. Isolates of the final population were more aggressive, and showed greater sporulation intensity under winter conditions and a shorter latency period (earlier sporulation) under spring conditions, than isolates of the initial population. These differences, complemented by lower between-genotype variability in the final population, exhibited an adaptation pattern with three striking features: (i) the pathogen responded synchronously to temperature and host stage conditions; (ii) the adaptation concerned two key fitness traits; (iii) adaptation to one trait (greater sporulation intensity) was expressed under winter conditions while, subsequently, adaptation to the other trait (shorter latency period) was expressed under spring conditions. This can be interpreted as the result of short term selection, driven by abiotic and biotic factors. This case study cannot yet be generalized but suggests that seasonality may play an important role in shaping the variability of fitness traits. These results further raise the question of possible counterselection during the interepidemic period. While we did not find any trade-off between clonal multiplication on leaves during the epidemic period and clonal spore production on debris, we suggest that final populations could be counterselected by an Allee effect, mitigating the potential impact of seasonal selection on long-term dynamics. PMID- 26150468 TI - Influence of prgH on the Persistence of Ingested Salmonella enterica in the Leafhopper Macrosteles quadrilineatus. AB - Phytophagous insects can encounter Salmonella enterica on contaminated plant surfaces and transmit externally adhered and internalized bacteria on and among leaves. Excretion of ingested S. enterica by the leafhopper Macrosteles quadrilineatus has been previously reported; however, the sites of persistence of ingested bacteria remain undetermined. Fluorescence microscopy revealed the presence and persistence of S. enterica in various organs of M. quadrilineatus fed an inoculated diet for 12 h and then moved to two consecutive noninoculated diets for a total of 48 h. Ingested S. enterica was predominantly observed in the filter chamber, midgut, and Malpighian tubules of M. quadrilineatus dissected immediately after acquisition and at 24- and 48-h post-acquisition access periods (post-AAPs). Additionally, we examined the potential roles of the Salmonella pathogenicity island 1 (SPI-1) and SPI-2 type III secretion systems (T3SSs) in the persistence and excretion of ingested S. enterica. In competition assays, a prgH mutant lacking a functional SPI-1 T3SS was recovered at significantly lower levels than the WT in insect homogenates at 24 h post-AAP, and complementation with prgH restored S. enterica persistence in M. quadrilineatus. Moreover, expression of prgH inside M. quadrilineatus was observed up to 48 post-AAP. No differences were observed between the WT and an ssaK mutant lacking a functional SPI-2 T3SS in insect homogenates or between the WT and either mutant in insect excretions. This study provides novel insight into the presence and persistence of S. enterica inside M. quadrilineatus and demonstrates that the SPI-1 T3SS influences the persistence of the pathogen in the gut of a potential vector. PMID- 26150469 TI - Novel pH-Stable Glycoside Hydrolase Family 3 beta-Xylosidase from Talaromyces amestolkiae: an Enzyme Displaying Regioselective Transxylosylation. AB - This paper reports on a novel beta-xylosidase from the hemicellulolytic fungus Talaromyces amestolkiae. The expression of this enzyme, called BxTW1, could be induced by beechwood xylan and was purified as a glycoprotein from culture supernatants. We characterized the gene encoding this enzyme as an intronless gene belonging to the glycoside hydrolase gene family 3 (GH3). BxTW1 exhibited transxylosylation activity in a regioselective way. This feature would allow the synthesis of oligosaccharides or other compounds not available from natural sources, such as alkyl glycosides displaying antimicrobial or surfactant properties. Regioselective transxylosylation, an uncommon combination, makes the synthesis reproducible, which is desirable for its potential industrial application. BxTW1 showed high pH stability and Cu(2+) tolerance. The enzyme displayed a pI of 7.6, a molecular mass around 200 kDa in its active dimeric form, and Km and Vmax values of 0.17 mM and 52.0 U/mg, respectively, using commercial p-nitrophenyl-beta-d-xylopyranoside as the substrate. The catalytic efficiencies for the hydrolysis of xylooligosaccharides were remarkably high, making it suitable for different applications in food and bioenergy industries. PMID- 26150470 TI - Copper Reduction and Contact Killing of Bacteria by Iron Surfaces. AB - The well-established killing of bacteria by copper surfaces, also called contact killing, is currently believed to be a combined effect of bacterial contact with the copper surface and the dissolution of copper, resulting in lethal bacterial damage. Iron can similarly be released in ionic form from iron surfaces and would thus be expected to also exhibit contact killing, although essentially no contact killing is observed by iron surfaces. However, we show here that the exposure of bacteria to iron surfaces in the presence of copper ions results in efficient contact killing. The process involves reduction of Cu(2+) to Cu(+) by iron; Cu(+) has been shown to be considerably more toxic to cells than Cu(2+). The specific Cu(+) chelator, bicinchoninic acid, suppresses contact killing by chelating the Cu(+) ions. These findings underline the importance of Cu(+) ions in the contact killing process and infer that iron-based alloys containing copper could provide novel antimicrobial materials. PMID- 26150471 TI - Catalase Expression Is Modulated by Vancomycin and Ciprofloxacin and Influences the Formation of Free Radicals in Staphylococcus aureus Cultures. AB - Detection of free radicals in biological systems is challenging due to their short half-lives. We have applied electron spin resonance (ESR) spectroscopy combined with spin traps using the probes PBN (N-tert-butyl-alpha-phenylnitrone) and DMPO (5,5-dimethyl-1-pyrroline N-oxide) to assess free radical formation in the human pathogen Staphylococcus aureus treated with a bactericidal antibiotic, vancomycin or ciprofloxacin. While we were unable to detect ESR signals in bacterial cells, hydroxyl radicals were observed in the supernatant of bacterial cell cultures. Surprisingly, the strongest signal was detected in broth medium without bacterial cells present and it was mitigated by iron chelation or by addition of catalase, which catalyzes the decomposition of hydrogen peroxide to water and oxygen. This suggests that the signal originates from hydroxyl radicals formed by the Fenton reaction, in which iron is oxidized by hydrogen peroxide. Previously, hydroxyl radicals have been proposed to be generated within bacterial cells in response to bactericidal antibiotics. We found that when S. aureus was exposed to vancomycin or ciprofloxacin, hydroxyl radical formation in the broth was indeed increased compared to the level seen with untreated bacterial cells. However, S. aureus cells express catalase, and the antibiotic-mediated increase in hydroxyl radical formation was correlated with reduced katA expression and catalase activity in the presence of either antibiotic. Therefore, our results show that in S. aureus, bactericidal antibiotics modulate catalase expression, which in turn influences the formation of free radicals in the surrounding broth medium. If similar regulation is found in other bacterial species, it might explain why bactericidal antibiotics are perceived as inducing formation of free radicals. PMID- 26150472 TI - CCND1-CDK4-mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo. AB - Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1-CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1-CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1-CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis. PMID- 26150474 TI - Electronic Monitoring in the Criminal Justice System: Less Recidivism? PMID- 26150473 TI - Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. AB - Adenylate kinases (AKs) are phosphotransferases that regulate the cellular adenine nucleotide composition and play a critical role in the energy homeostasis of all tissues. The AK2 isoenzyme is expressed in the mitochondrial intermembrane space and is mutated in reticular dysgenesis (RD), a rare form of severe combined immunodeficiency (SCID) in humans. RD is characterized by a maturation arrest in the myeloid and lymphoid lineages, leading to early onset, recurrent, and overwhelming infections. To gain insight into the pathophysiology of RD, we studied the effects of AK2 deficiency using the zebrafish model and induced pluripotent stem cells (iPSCs) derived from fibroblasts of an RD patient. In zebrafish, Ak2 deficiency affected hematopoietic stem and progenitor cell (HSPC) development with increased oxidative stress and apoptosis. AK2-deficient iPSCs recapitulated the characteristic myeloid maturation arrest at the promyelocyte stage and demonstrated an increased AMP/ADP ratio, indicative of an energy depleted adenine nucleotide profile. Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish and restored differentiation of AK2-deficient iPSCs into mature granulocytes. Our results link hematopoietic cell fate in AK2 deficiency to cellular energy depletion and increased oxidative stress. This points to the potential use of antioxidants as a supportive therapeutic modality for patients with RD. PMID- 26150475 TI - Expression and clinicopathological significance of microRNA-21 and programmed cell death 4 in malignant melanoma. AB - OBJECTIVE: To measure levels of microRNA (miR)-21 and its target gene, programmed cell death 4 (PDCD4), in samples of human cutaneous malignant melanoma and normal non-malignant control skin. METHODS: Relative levels of miR-21 and PDCD4 mRNA were measured using a quantitative real-time reverse transcription-polymerase chain reaction. Correlations between the levels of the two molecules and the clinicopathological characteristics of malignant melanoma were analysed. RESULTS: A total of 67 cases of human cutaneous malignant melanoma were analysed and compared with 67 samples of normal nonmalignant control skin. Compared with normal skin samples, the relative level of miR-21 was significantly higher and the relative level of PDCD4 mRNA was significantly lower in the melanoma specimens. A significant negative correlation between PDCD4 mRNA and miR-21 was demonstrated in malignant melanoma (r = -0.602). Elevated miR-21 and reduced PDCD4 mRNA levels were both significantly correlated with increased tumour size, a higher Clark classification level and the presence of lymph node metastases in malignant melanoma. CONCLUSIONS: These findings suggest that miR-21 and PDCD4 might be potential biomarkers for malignant melanoma and might provide treatment targets in the future. PMID- 26150476 TI - Traditional Risk Factors Versus Biomarkers for Prediction of Secondary Events in Patients With Stable Coronary Heart Disease: From the Heart and Soul Study. AB - BACKGROUND: Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD. METHODS AND RESULTS: We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin:creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort. CONCLUSIONS: Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD. PMID- 26150477 TI - Relationship Between Cancer and Cardiovascular Outcomes Following Percutaneous Coronary Intervention. AB - BACKGROUND: Cardiovascular disease and cancer increasingly coexist, yet relationships between cancer and long-term cardiovascular outcomes post percutaneous coronary intervention (PCI) are not well studied. METHODS AND RESULTS: We examined stented PCI patients at Duke (1996-2010) using linked data from the Duke Information Systems for Cardiovascular Care and the Duke Tumor Registry (a cancer treatment registry). Our primary outcome was cardiovascular mortality. Secondary outcomes included composite cardiovascular mortality, myocardial infarction, or repeat revascularization and all-cause mortality. We used adjusted cause-specific hazard models to examine outcomes among cancer patients (cancer treatment pre-PCI) versus controls (no cancer treatment pre PCI). Cardiovascular mortality was explored in a cancer subgroup with recent (within 1 year pre-PCI) cancer and in post-PCI cancer patients using post-PCI cancer as a time-dependent variable. Among 15 008 patients, 3.3% (n=496) were cancer patients. Observed rates of 14-year cardiovascular mortality (31.4% versus 27.7%, P=0.31) and composite cardiovascular death, myocardial infarction, or revascularization (51.1% versus 55.8%, P=0.37) were similar for cancer versus control groups; all-cause mortality rates were higher (79.7% versus 49.3%, P<0.01). Adjusted risk of cardiovascular mortality was similar for cancer patients versus controls (hazard ratio 0.95; 95% CI 0.76 to 1.20) and for patients with versus without recent cancer (hazard ratio 1.46; 95% CI 0.92 to 2.33). Post-PCI cancer, present in 4.3% (n=647) of patients, was associated with cardiovascular mortality (adjusted hazard ratio 1.51; 95% CI 1.11 to 2.03). CONCLUSIONS: Cancer history was present in a minority of PCI patients but was not associated with worse long-term cardiovascular outcomes. Further investigation into PCI outcomes in this population is warranted. PMID- 26150478 TI - Mass Media Campaigns' Influence on Prehospital Behavior for Acute Coronary Syndromes: An Evaluation of the Australian Heart Foundation's Warning Signs Campaign. AB - BACKGROUND: The aim of this study was to examine the awareness of a recent mass media campaign, and its influence on knowledge and prehospital times, in a cohort of acute coronary syndrome (ACS) patients admitted to an Australian hospital. METHODS AND RESULTS: We conducted 199 semistructured interviews with consecutive ACS patients who were aged 35 to 75 years, competent to provide consent, and English speaking. Questions addressed the factors known to predict prehospital delay, awareness of the campaign, and whether it increased knowledge and influenced actions. Multivariable logistic regression was used to examine the association between campaign awareness and a 1-hour delay in deciding to seek medical attention (patient delay) and a 2-hour delay in presenting to hospital (prehospital delay). The median age was 62 years (IQR=53 to 68 years), and 68% (n=136) were male. Awareness of the campaign was reported by 127 (64%) patients, with most of these patients stating the campaign (1) increased their understanding of what is a heart attack (63%), (2) increased their awareness of the signs and symptoms of heart attack (68%), and (3) influenced their actions in response to symptoms (43%). After adjustment for other predictors, awareness of the campaign was significantly associated with patient delay time of <=1 hour (adjusted odds ratio [AOR]=2.25, 95% CI: 1.03 to 4.91, P=0.04) and prehospital delay time <=2 hours (AOR=3.11, 95% CI: 1.36 to 7.08, P=0.007). CONCLUSIONS: Our study showed reasonably high awareness of the warning signs campaign, which was significantly associated with shorter prehospital decision-making and faster presentation to hospital. PMID- 26150479 TI - Sex Disparities in Stroke: Women Have More Severe Strokes but Better Survival Than Men. AB - BACKGROUND: Uncertainty remains about whether stroke affects men and women similarly. We studied differences between men and women with regard to stroke severity and survival. METHODS AND RESULTS: We used the Danish Stroke Registry, with information on all hospital admissions for stroke in Denmark between 2003 and 2012 (N=79 617), and the Danish Register of Causes of Death. Information was available on age, sex, marital status, stroke severity, stroke subtype, socioeconomic status, and cardiovascular risk profile. We studied only deaths due to the index stroke, with the assumption that death reported on death certificates as due to stroke was related to the index stroke if death occurred within the first week or month after stroke. Multivariate Cox regression analysis and multiple imputation were applied. Stroke was the cause of death for 4373 and 5512 of the 79 617 patients within 1 week (5.5%) or 1 month (6.9%), respectively. After the age of 60 years, women had more severe strokes than men. Up to ages in the mid-60s, no difference in the risk of death from stroke was seen between the 2 sexes. For people aged >65 years, however, the risk gradually became greater in men than in women and significantly so (>15%) from the mid-70s (adjusted for age, marital status, stroke severity, stroke subtype, socioeconomic status, and cardiovascular risk factors). Results were essentially the same when analyzing deaths within 1 week, 1 month and ischemic and hemorrhagic stroke separately. CONCLUSIONS: Stroke affects women and men differently. Elderly women were affected more severely than elderly men but were more likely to survive. PMID- 26150480 TI - Intergenerational neural mediators of early-life anxious temperament. AB - Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolism-not brain structure-that is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology. PMID- 26150482 TI - Anomalous scaling law of strength and toughness of cellulose nanopaper. AB - The quest for both strength and toughness is perpetual in advanced material design; unfortunately, these two mechanical properties are generally mutually exclusive. So far there exists only limited success of attaining both strength and toughness, which often needs material-specific, complicated, or expensive synthesis processes and thus can hardly be applicable to other materials. A general mechanism to address the conflict between strength and toughness still remains elusive. Here we report a first-of-its-kind study of the dependence of strength and toughness of cellulose nanopaper on the size of the constituent cellulose fibers. Surprisingly, we find that both the strength and toughness of cellulose nanopaper increase simultaneously (40 and 130 times, respectively) as the size of the constituent cellulose fibers decreases (from a mean diameter of 27 MUm to 11 nm), revealing an anomalous but highly desirable scaling law of the mechanical properties of cellulose nanopaper: the smaller, the stronger and the tougher. Further fundamental mechanistic studies reveal that reduced intrinsic defect size and facile (re)formation of strong hydrogen bonding among cellulose molecular chains is the underlying key to this new scaling law of mechanical properties. These mechanistic findings are generally applicable to other material building blocks, and therefore open up abundant opportunities to use the fundamental bottom-up strategy to design a new class of functional materials that are both strong and tough. PMID- 26150481 TI - Vacuolar ATPase depletion affects mitochondrial ATPase function, kinetoplast dependency, and drug sensitivity in trypanosomes. AB - Kinetoplastid parasites cause lethal diseases in humans and animals. The kinetoplast itself contains the mitochondrial genome, comprising a huge, complex DNA network that is also an important drug target. Isometamidium, for example, is a key veterinary drug that accumulates in the kinetoplast in African trypanosomes. Kinetoplast independence and isometamidium resistance are observed where certain mutations in the F1-gamma-subunit of the two-sector F1Fo-ATP synthase allow for Fo-independent generation of a mitochondrial membrane potential. To further explore kinetoplast biology and drug resistance, we screened a genome-scale RNA interference library in African trypanosomes for isometamidium resistance mechanisms. Our screen identified 14 V-ATPase subunits and all 4 adaptin-3 subunits, implicating acidic compartment defects in resistance; V-ATPase acidifies lysosomes and related organelles, whereas adaptin 3 is responsible for trafficking among these organelles. Independent strains with depleted V-ATPase or adaptin-3 subunits were isometamidium resistant, and chemical inhibition of the V-ATPase phenocopied this effect. While drug accumulation in the kinetoplast continued after V-ATPase subunit depletion, acriflavine-induced kinetoplast loss was specifically tolerated in these cells and in cells depleted for adaptin-3 or endoplasmic reticulum membrane complex subunits, also identified in our screen. Consistent with kinetoplast dispensability, V-ATPase defective cells were oligomycin resistant, suggesting ATP synthase uncoupling and bypass of the normal Fo-A6-subunit requirement; this subunit is the only kinetoplast-encoded product ultimately required for viability in bloodstream-form trypanosomes. Thus, we describe 30 genes and 3 protein complexes associated with kinetoplast-dependent growth. Mutations affecting these genes could explain natural cases of dyskinetoplasty and multidrug resistance. Our results also reveal potentially conserved communication between the compartmentalized two-sector rotary ATPases. PMID- 26150483 TI - Graphene electrostatic microphone and ultrasonic radio. AB - We present a graphene-based wideband microphone and a related ultrasonic radio that can be used for wireless communication. It is shown that graphene-based acoustic transmitters and receivers have a wide bandwidth, from the audible region (20~20 kHz) to the ultrasonic region (20 kHz to at least 0.5 MHz). Using the graphene-based components, we demonstrate efficient high-fidelity information transmission using an ultrasonic band centered at 0.3 MHz. The graphene-based microphone is also shown to be capable of directly receiving ultrasound signals generated by bats in the field, and the ultrasonic radio, coupled to electromagnetic (EM) radio, is shown to function as a high-accuracy rangefinder. The ultrasonic radio could serve as a useful addition to wireless communication technology where the propagation of EM waves is difficult. PMID- 26150485 TI - Reanalysis of parabiosis of obesity mutants in the age of leptin. AB - In this study we set out to explain the differing effects of parabiosis with genetically diabetic (db) mice versus administration of recombinant leptin. Parabiosis of db mutant, which overexpress leptin, to wildtype (WT) or genetically obese (ob) mice has been reported to cause death by starvation, whereas leptin infusions do not produce lethality at any dose or mode of delivery tested. Leptin is not posttranslationally modified other than a single disulphide bond, raising the possibility that it might require additional factor(s) to exert the maximal appetite-suppressing effect. We reconfirmed the lethal effect of parabiosis of db mutant on WT mice and further showed that this lethality could not be rescued by administration of ghrelin or growth hormone. We then initiated a biochemical fractionation of a high-molecular-weight leptin complex from human plasma and identified clusterin as a major component of this leptin-containing complex. However, in contrast to previous reports, we failed to observe a leptin potentiating effect of either exogenous or endogenous clusterin, and parabiosis of db clusterin(-/-) double-mutant to WT mice still caused lethality. Intriguingly, in parabiotic pairs of two WT mice, leptin infusion into one of the mice led to an enhanced starvation response during calorie restriction as evidenced by increased plasma ghrelin and growth-hormone levels. Moreover, leptin treatment resulted in death of the parabiotic pairs. These data suggest that the appetite suppression in WT mice after parabiosis to db mutants is the result of induced hyperleptinemia combined with the stress or other aspect(s) of the parabiosis procedure. PMID- 26150484 TI - In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells. AB - "Cafe-au-lait" macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases. PMID- 26150486 TI - Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters. AB - Large-scale sequencing of prokaryotic (meta)genomic DNA suggests that most bacterial natural product gene clusters are not expressed under common laboratory culture conditions. Silent gene clusters represent a promising resource for natural product discovery and the development of a new generation of therapeutics. Unfortunately, the characterization of molecules encoded by these clusters is hampered owing to our inability to express these gene clusters in the laboratory. To address this bottleneck, we have developed a promoter-engineering platform to transcriptionally activate silent gene clusters in a model heterologous host. Our approach uses yeast homologous recombination, an auxotrophy complementation-based yeast selection system and sequence orthogonal promoter cassettes to exchange all native promoters in silent gene clusters with constitutively active promoters. As part of this platform, we constructed and validated a set of bidirectional promoter cassettes consisting of orthogonal promoter sequences, Streptomyces ribosome binding sites, and yeast selectable marker genes. Using these tools we demonstrate the ability to simultaneously insert multiple promoter cassettes into a gene cluster, thereby expediting the reengineering process. We apply this method to model active and silent gene clusters (rebeccamycin and tetarimycin) and to the silent, cryptic pseudogene containing, environmental DNA-derived Lzr gene cluster. Complete promoter refactoring and targeted gene exchange in this "dead" cluster led to the discovery of potent indolotryptoline antiproliferative agents, lazarimides A and B. This potentially scalable and cost-effective promoter reengineering platform should streamline the discovery of natural products from silent natural product biosynthetic gene clusters. PMID- 26150487 TI - Photodrive of magnetic bubbles via magnetoelastic waves. AB - Precise control of magnetic domain walls continues to be a central topic in the field of spintronics to boost infotech, logic, and memory applications. One way is to drive the domain wall by current in metals. In insulators, the incoherent flow of phonons and magnons induced by the temperature gradient can carry the spins, i.e., spin Seebeck effect, but the spatial and time dependence is difficult to control. Here, we report that coherent phonons hybridized with spin waves, magnetoelastic waves, can drive magnetic bubble domains, or curved domain walls, in an iron garnet, which are excited by ultrafast laser pulses at a nonabsorbing photon energy. These magnetoelastic waves were imaged by time resolved Faraday microscopy, and the resultant spin transfer force was evaluated to be larger for domain walls with steeper curvature. This will pave a path for the rapid spatiotemporal control of magnetic textures in insulating magnets. PMID- 26150488 TI - The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche. AB - The maintenance of stem or progenitor cell fate relies on intrinsic factors as well as local cues from the cellular microenvironment and systemic signaling. In the lymph gland, an hematopoietic organ in Drosophila larva, a group of cells called the Posterior Signaling Centre (PSC), whose specification depends on the EBF transcription factor Collier (Col) and the HOX factor Antennapedia (Antp), has been proposed to form a niche required to maintain the pool of hematopoietic progenitors (prohemocytes). In contrast with this model, we show here that genetic ablation of the PSC does not cause an increase in blood cell differentiation or a loss of blood cell progenitors. Furthermore, although both col and Antp mutant larvae are devoid of PSC, the massive prohemocyte differentiation observed in col mutant is not phenocopied in Antp mutant. Interestingly, beside its expression in the PSC, Col is also expressed at low levels in prohemocytes and we show that this expression persists in PSC-ablated and Antp mutant larvae. Moreover, targeted knockdown and rescue experiments indicate that Col expression is required in the prohemocytes to prevent their differentiation. Together, our findings show that the PSC is dispensable for blood cell progenitor maintenance and reveal the key role of the conserved transcription factor Col as an intrinsic regulator of hematopoietic progenitor fate. PMID- 26150489 TI - Sequential ubiquitination and deubiquitination enzymes synchronize the dual sensor and effector functions of TRIM21. AB - Tripartite motif (TRIM) 21 is a cytosolic antibody receptor that neutralizes antibody-coated viruses that penetrate the cell and simultaneously activates innate immunity. Here we show that the conjugation of TRIM21 with K63-linked ubiquitin (Ub-(63)Ub) catalyzed by the sequential activity of nonredundant E2 Ub enzymes is required for its dual antiviral functions. TRIM21 is first labeled with monoubiquitin (monoUb) by the E2 Ube2W. The monoUb is a substrate for the heterodimeric E2 Ube2N/Ube2V2, resulting in TRIM21-anchored Ub-(63)Ub. Depletion of either E2 abolishes Ub-(63)Ub and Ub-(48)Ub conjugation of TRIM21, NF-kappaB signaling, and virus neutralization. The formation of TRIM21-Ub-(63)Ub precedes proteasome recruitment, and we identify an essential role for the 19S-resident and degradation-coupled deubiquitinase Poh1 in TRIM21 neutralization, signaling, and cytokine induction. This study elucidates a complex mechanism of step-wise ubiquitination and deubiquitination activities that allows contemporaneous innate immune signaling and neutralization by TRIM21. PMID- 26150491 TI - Drivers for the renaissance of coal. AB - Coal was central to the industrial revolution, but in the 20th century it increasingly was superseded by oil and gas. However, in recent years coal again has become the predominant source of global carbon emissions. We show that this trend of rapidly increasing coal-based emissions is not restricted to a few individual countries such as China. Rather, we are witnessing a global renaissance of coal majorly driven by poor, fast-growing countries that increasingly rely on coal to satisfy their growing energy demand. The low price of coal relative to gas and oil has played an important role in accelerating coal consumption since the end of the 1990s. In this article, we show that in the increasingly integrated global coal market the availability of a domestic coal resource does not have a statistically significant impact on the use of coal and related emissions. These findings have important implications for climate change mitigation: If future economic growth of poor countries is fueled mainly by coal, ambitious mitigation targets very likely will become infeasible. Building new coal power plant capacities will lead to lock-in effects for the next few decades. If that lock-in is to be avoided, international climate policy must find ways to offer viable alternatives to coal for developing countries. PMID- 26150490 TI - Chloroplasts extend stromules independently and in response to internal redox signals. AB - A fundamental mystery of plant cell biology is the occurrence of "stromules," stroma-filled tubular extensions from plastids (such as chloroplasts) that are universally observed in plants but whose functions are, in effect, completely unknown. One prevalent hypothesis is that stromules exchange signals or metabolites between plastids and other subcellular compartments, and that stromules are induced during stress. Until now, no signaling mechanisms originating within the plastid have been identified that regulate stromule activity, a critical missing link in this hypothesis. Using confocal and superresolution 3D microscopy, we have shown that stromules form in response to light-sensitive redox signals within the chloroplast. Stromule frequency increased during the day or after treatment with chemicals that produce reactive oxygen species specifically in the chloroplast. Silencing expression of the chloroplast NADPH-dependent thioredoxin reductase, a central hub in chloroplast redox signaling pathways, increased chloroplast stromule frequency, whereas silencing expression of nuclear genes related to plastid genome expression and tetrapyrrole biosynthesis had no impact on stromules. Leucoplasts, which are not photosynthetic, also made more stromules in the daytime. Leucoplasts did not respond to the same redox signaling pathway but instead increased stromule formation when exposed to sucrose, a major product of photosynthesis, although sucrose has no impact on chloroplast stromule frequency. Thus, different types of plastids make stromules in response to distinct signals. Finally, isolated chloroplasts could make stromules independently after extraction from the cytoplasm, suggesting that chloroplast-associated factors are sufficient to generate stromules. These discoveries demonstrate that chloroplasts are remarkably autonomous organelles that alter their stromule frequency in reaction to internal signal transduction pathways. PMID- 26150492 TI - What the fly's nose tells the fly's brain. AB - The fly olfactory system has a three-layer architecture: The fly's olfactory receptor neurons send odor information to the first layer (the encoder) where this information is formatted as combinatorial odor code, one which is maximally informative, with the most informative neurons firing fastest. This first layer then sends the encoded odor information to the second layer (decoder), which consists of about 2,000 neurons that receive the odor information and "break" the code. For each odor, the amplitude of the synaptic odor input to the 2,000 second layer neurons is approximately normally distributed across the population, which means that only a very small fraction of neurons receive a large input. Each odor, however, activates its own population of large-input neurons and so a small subset of the 2,000 neurons serves as a unique tag for the odor. Strong inhibition prevents most of the second-stage neurons from firing spikes, and therefore spikes from only the small population of large-input neurons is relayed to the third stage. This selected population provides the third stage (the user) with an odor label that can be used to direct behavior based on what odor is present. PMID- 26150493 TI - How fish power suction feeding. PMID- 26150495 TI - Three-ring circus without a ringmaster: Self-organization of supracellular actin ring patterns during epithelial morphogenesis. PMID- 26150494 TI - Optimized deep-targeted proteotranscriptomic profiling reveals unexplored Conus toxin diversity and novel cysteine frameworks. AB - Cone snails are predatory marine gastropods characterized by a sophisticated venom apparatus responsible for the biosynthesis and delivery of complex mixtures of cysteine-rich toxin peptides. These conotoxins fold into small highly structured frameworks, allowing them to potently and selectively interact with heterologous ion channels and receptors. Approximately 2,000 toxins from an estimated number of >70,000 bioactive peptides have been identified in the genus Conus to date. Here, we describe a high-resolution interrogation of the transcriptomes (available at www.ddbj.nig.ac.jp) and proteomes of the diverse compartments of the Conus episcopatus venom apparatus. Using biochemical and bioinformatic tools, we found the highest number of conopeptides yet discovered in a single Conus specimen, with 3,305 novel precursor toxin sequences classified into 9 known superfamilies (A, I1, I2, M, O1, O2, S, T, Z), and identified 16 new superfamilies showing unique signal peptide signatures. We were also able to depict the largest population of venom peptides containing the pharmacologically active C-C-CC-C-C inhibitor cystine knot and CC-C-C motifs (168 and 44 toxins, respectively), as well as 208 new conotoxins displaying odd numbers of cysteine residues derived from known conotoxin motifs. Importantly, six novel cysteine rich frameworks were revealed which may have novel pharmacology. Finally, analyses of codon usage bias and RNA-editing processes of the conotoxin transcripts demonstrate a specific conservation of the cysteine skeleton at the nucleic acid level and provide new insights about the origin of sequence hypervariablity in mature toxin regions. PMID- 26150496 TI - Insular neural system controls decision-making in healthy and methamphetamine treated rats. AB - Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making. PMID- 26150498 TI - Rapid and widespread de novo evolution of kin discrimination. AB - Diverse forms of kin discrimination, broadly defined as alteration of social behavior as a function of genetic relatedness among interactants, are common among social organisms from microbes to humans. However, the evolutionary origins and causes of kin-discriminatory behavior remain largely obscure. One form of kin discrimination observed in microbes is the failure of genetically distinct colonies to merge freely upon encounter. Here, we first use natural isolates of the highly social bacterium Myxococcus xanthus to show that colony-merger incompatibilities can be strong barriers to social interaction, particularly by reducing chimerism in multicellular fruiting bodies that develop near colony territory borders. We then use experimental laboratory populations to test hypotheses regarding the evolutionary origins of kin discrimination. We show that the generic process of adaptation, irrespective of selective environment, is sufficient to repeatedly generate kin-discriminatory behaviors between evolved populations and their common ancestor. Further, we find that kin discrimination pervasively evolves indirectly between allopatric replicate populations that adapt to the same ecological habitat and that this occurs generically in many distinct habitats. Patterns of interpopulation discrimination imply that kin discrimination phenotypes evolved via many diverse genetic mechanisms and mutation-accumulation patterns support this inference. Strong incompatibility phenotypes emerged abruptly in some populations but strengthened gradually in others. The indirect evolution of kin discrimination in an asexual microbe is analogous to the indirect evolution of reproductive incompatibility in sexual eukaryotes and linguistic incompatibility among human cultures, the commonality being indirect, noncoordinated divergence of complex systems evolving in isolation. PMID- 26150497 TI - Quantification of biological aging in young adults. AB - Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their "biological aging" (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies. PMID- 26150499 TI - Measuring selective constraint on fertility in human life histories. AB - Human life histories combine late age at first reproduction, long reproductive span, relatively high fertility, and substantial postreproductive survival. However, even among the most fecund populations, human fertility falls far below its theoretical maximum. The extent of parental care required for successful offspring recruitment and widespread fertility decline under proper economic conditions suggest that selection on fertility is constrained by trade-offs with recruitment. Here we measure the trade-offs between life history traits under selection by approximating the slope of the selective constraint curve on two traits at the observed values. Using a selection of populations that span human demographic space, we find that the substitution elasticity of fertility for infant survival shows age-related patterns, with minimum substitution elasticities ranging from 14 to 22 for the four populations. The age of this minimum occurs earlier in the high-mortality populations relative to generation time than it does in the low-mortality populations. The human curves are qualitatively similar to one of two comparable nonhuman primate age-specific substitution elasticity curves. The curve for rhesus macaques has a similar shape but is shifted down, meaning that the threshold for switching from investing in survival to fertility is lower at all ages. The magnitude of the substitution elasticities is similar between chimpanzees and humans but the shape is quite different, rising more slowly for a longer fraction of the chimpanzee life cycle. The steeply rising substitution elasticities with age in humans has clear implications for the evolution of reproductive senescence. PMID- 26150500 TI - Identification of divergent type VI secretion effectors using a conserved chaperone domain. AB - The type VI secretion system (T6SS) is a lethal weapon used by many bacteria to kill eukaryotic predators or prokaryotic competitors. Killing by the T6SS results from repetitive delivery of toxic effectors. Despite their importance in dictating bacterial fitness, systematic prediction of T6SS effectors remains challenging due to high effector diversity and the absence of a conserved signature sequence. Here, we report a class of T6SS effector chaperone (TEC) proteins that are required for effector delivery through binding to VgrG and effector proteins. The TEC proteins share a highly conserved domain (DUF4123) and are genetically encoded upstream of their cognate effector genes. Using the conserved TEC domain sequence, we identified a large family of TEC genes coupled to putative T6SS effectors in Gram-negative bacteria. We validated this approach by verifying a predicted effector TseC in Aeromonas hydrophila. We show that TseC is a T6SS-secreted antibacterial effector and that the downstream gene tsiC encodes the cognate immunity protein. Further, we demonstrate that TseC secretion requires its cognate TEC protein and an associated VgrG protein. Distinct from previous effector-dependent bioinformatic analyses, our approach using the conserved TEC domain will facilitate the discovery and functional characterization of new T6SS effectors in Gram-negative bacteria. PMID- 26150501 TI - Biased Brownian motion as a mechanism to facilitate nanometer-scale exploration of the microtubule plus end by a kinesin-8. AB - Kinesin-8s are plus-end-directed motors that negatively regulate microtubule (MT) length. Well-characterized members of this subfamily (Kip3, Kif18A) exhibit two important properties: (i) They are "ultraprocessive," a feature enabled by a second MT-binding site that tethers the motors to a MT track, and (ii) they dissociate infrequently from the plus end. Together, these characteristics combined with their plus-end motility cause Kip3 and Kif18A to enrich preferentially at the plus ends of long MTs, promoting MT catastrophes or pausing. Kif18B, an understudied human kinesin-8, also limits MT growth during mitosis. In contrast to Kif18A and Kip3, localization of Kif18B to plus ends relies on binding to the plus-end tracking protein EB1, making the relationship between its potential plus-end-directed motility and plus-end accumulation unclear. Using single-molecule assays, we show that Kif18B is only modestly processive and that the motor switches frequently between directed and diffusive modes of motility. Diffusion is promoted by the tail domain, which also contains a second MT-binding site that decreases the off rate of the motor from the MT lattice. In cells, Kif18B concentrates at the extreme tip of a subset of MTs, superseding EB1. Our data demonstrate that kinesin-8 motors use diverse design principles to target MT plus ends, which likely target them to the plus ends of distinct MT subpopulations in the mitotic spindle. PMID- 26150502 TI - Inferring influenza dynamics and control in households. AB - Household-based interventions are the mainstay of public health policy against epidemic respiratory pathogens when vaccination is not available. Although the efficacy of these interventions has traditionally been measured by their ability to reduce the proportion of household contacts who exhibit symptoms [household secondary attack rate (hSAR)], this metric is difficult to interpret and makes only partial use of data collected by modern field studies. Here, we use Bayesian transmission model inference to analyze jointly both symptom reporting and viral shedding data from a three-armed study of influenza interventions. The reduction in hazard of infection in the increased hand hygiene intervention arm was 37.0% [8.3%, 57.8%], whereas the equivalent reduction in the other intervention arm was 27.2% [-0.46%, 52.3%] (increased hand hygiene and face masks). By imputing the presence and timing of unobserved infection, we estimated that only 61.7% [43.1%, 76.9%] of infections met the case criteria and were thus detected by the study design. An assessment of interventions using inferred infections produced more intuitively consistent attack rates when households were stratified by the speed of intervention, compared with the crude hSAR. Compared with adults, children were 2.29 [1.66, 3.23] times as infectious and 3.36 [2.31, 4.82] times as susceptible. The mean generation time was 3.39 d [3.06, 3.70]. Laboratory confirmation of infections by RT-PCR was only able to detect 79.6% [76.5%, 83.0%] of symptomatic infections, even at the peak of shedding. Our results highlight the potential use of robust inference with well-designed mechanistic transmission models to improve the design of intervention studies. PMID- 26150503 TI - PDGFB-based stem cell gene therapy increases bone strength in the mouse. AB - Substantial advances have been made in the past two decades in the management of osteoporosis. However, none of the current medications can eliminate the risk of fracture and rejuvenate the skeleton. To this end, we recently reported that transplantation of hematopoietic stem/progenitor cells (HSCs) or Sca1(+) cells engineered to overexpress FGF2 results in a significant increase in lamellar bone matrix formation at the endosteum; but this increase was attended by the development of secondary hyperparathyroidism and severe osteomalacia. Here we switch the therapeutic gene to PDGFB, another potent mitogen for mesenchymal stem cells (MSCs) but potentially safer than FGF2. We found that modest overexpression of PDGFB using a relatively weak phosphoglycerate kinase (PGK) promoter completely avoided osteomalacia and secondary hyperparathyroidism, and simultaneously increased trabecular bone formation and trabecular connectivity, and decreased cortical porosity. These effects led to a 45% increase in the bone strength. Transplantation of PGK-PDGFB-transduced Sca1(+) cells increased MSC proliferation, raising the possibility that PDGF-BB enhances expansion of MSC in the vicinity of the hematopoietic niche where the osteogenic milieu propels the differentiation of MSCs toward an osteogenic destination. Our therapy should have potential clinical applications for patients undergoing HSC transplantation, who are at high risk for osteoporosis and bone fractures after total body irradiation preconditioning. It could eventually have wider application once the therapy can be applied without the preconditioning. PMID- 26150504 TI - Long noncoding RNA derived from CD244 signaling epigenetically controls CD8+ T cell immune responses in tuberculosis infection. AB - Molecular mechanisms for T-cell immune responses modulated by T cell-inhibitory molecules during tuberculosis (TB) infection remain unclear. Here, we show that active human TB infection up-regulates CD244 and CD244 signaling-associated molecules in CD8(+) T cells and that blockade of CD244 signaling enhances production of IFN-gamma and TNF-alpha. CD244 expression/signaling in TB correlates with high levels of a long noncoding RNA (lncRNA)-BC050410 [named as lncRNA-AS-GSTT1(1-72) or lncRNA-CD244] in the CD244(+)CD8(+) T-cell subpopulation. CD244 signaling drives lncRNA-CD244 expression via sustaining a permissive chromatin state in the lncRNA-CD244 locus. By recruiting polycomb protein enhancer of zeste homolog 2 (EZH2) to infg/tnfa promoters, lncRNA-CD244 mediates H3K27 trimethylation at infg/tnfa loci toward repressive chromatin states and inhibits IFN-gamma/TNF-alpha expression in CD8(+) T cells. Such inhibition can be reversed by knock down of lncRNA-CD244. Interestingly, adoptive transfer of lncRNA-CD244-depressed CD8(+) T cells to Mycobacterium tuberculosis (MTB)-infected mice reduced MTB infection and TB pathology compared with lncRNA CD244-expressed controls. Thus, this work uncovers previously unidentified mechanisms in which T cell-inhibitory signaling and lncRNAs regulate T-cell responses and host defense against TB infection. PMID- 26150505 TI - Limits and patterns of cytomegalovirus genomic diversity in humans. AB - Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congenitally infected infants. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with ~ 25% of the genome being devoid of polymorphisms. These low diversity regions were distributed across 26 loci that were preferentially located in DNA-processing genes. Furthermore, by developing, to our knowledge, the first genome-wide mutation and recombination rate maps for HCMV, we show that genomic diversity is positively correlated with these two rates. In contrast, median levels of viral genomic diversity did not vary between putatively single or mixed strain infections. We also provide evidence that HCMV populations isolated from vascular compartments of hosts from different continents are genetically similar and that polymorphisms in glycoproteins and regulatory proteins are enriched in these viral populations. This analysis provides the most highly detailed map of HCMV genomic diversity in human hosts to date and informs our understanding of the distribution of HCMV genomic diversity within human hosts. PMID- 26150506 TI - Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain. AB - Despite intensive effort and resulting gains in understanding the mechanisms underlying neuropathic pain, limited success in therapeutic approaches have been attained. A recently identified, nonchannel, nonneurotransmitter therapeutic target for pain is the enzyme soluble epoxide hydrolase (sEH). The sEH degrades natural analgesic lipid mediators, epoxy fatty acids (EpFAs), therefore its inhibition stabilizes these bioactive mediators. Here we demonstrate the effects of EpFAs on diabetes induced neuropathic pain and define a previously unknown mechanism of pain, regulated by endoplasmic reticulum (ER) stress. The activation of ER stress is first quantified in the peripheral nervous system of type I diabetic rats. We demonstrate that both pain and markers of ER stress are reversed by a chemical chaperone. Next, we identify the EpFAs as upstream modulators of ER stress pathways. Chemical inducers of ER stress invariably lead to pain behavior that is reversed by a chemical chaperone and an inhibitor of sEH. The rapid occurrence of pain behavior with inducers, equally rapid reversal by blockers and natural incidence of ER stress in diabetic peripheral nervous system (PNS) argue for a major role of the ER stress pathways in regulating the excitability of the nociceptive system. Understanding the role of ER stress in generation and maintenance of pain opens routes to exploit this system for therapeutic purposes. PMID- 26150507 TI - Twentieth century surge of excess adult male mortality. AB - Using historical data from 1,763 birth cohorts from 1800 to 1935 in 13 developed countries, we show that what is now seen as normal-a large excess of female life expectancy in adulthood-is a demographic phenomenon that emerged among people born in the late 1800s. We show that excess adult male mortality is clearly rooted in specific age groups, 50-70, and that the sex asymmetry emerged in cohorts born after 1880 when male:female mortality ratios increased by as much as 50% from a baseline of about 1.1. Heart disease is the main condition associated with increased excess male mortality for those born after 1900. We further show that smoking-attributable deaths account for about 30% of excess male mortality at ages 50-70 for cohorts born in 1900-1935. However, after accounting for smoking, substantial excess male mortality at ages 50-70 remained, particularly from cardiovascular disease. The greater male vulnerability to cardiovascular conditions emerged with the reduction in infectious mortality and changes in health-related behaviors. PMID- 26150508 TI - Measuring dynamic cell-material interactions and remodeling during 3D human mesenchymal stem cell migration in hydrogels. AB - Biomaterials that mimic aspects of the extracellular matrix by presenting a 3D microenvironment that cells can locally degrade and remodel are finding increased applications as wound-healing matrices, tissue engineering scaffolds, and even substrates for stem cell expansion. In vivo, cells do not simply reside in a static microenvironment, but instead, they dynamically reengineer their surroundings. For example, cells secrete proteases that degrade extracellular components, attach to the matrix through adhesive sites, and can exert traction forces on the local matrix, causing its spatial reorganization. Although biomaterials scaffolds provide initially well-defined microenvironments for 3D culture of cells, less is known about the changes that occur over time, especially local matrix remodeling that can play an integral role in directing cell behavior. Here, we use microrheology as a quantitative tool to characterize dynamic cellular remodeling of peptide-functionalized poly(ethylene glycol) (PEG) hydrogels that degrade in response to cell-secreted matrix metalloproteinases (MMPs). This technique allows measurement of spatial changes in material properties during migration of encapsulated cells and has a sensitivity that identifies regions where cells simply adhere to the matrix, as well as the extent of local cell remodeling of the material through MMP-mediated degradation. Collectively, these microrheological measurements provide insight into microscopic, cellular manipulation of the pericellular region that gives rise to macroscopic tracks created in scaffolds by migrating cells. This quantitative and predictable information should benefit the design of improved biomaterial scaffolds for medically relevant applications. PMID- 26150509 TI - Conserved regulatory mechanism controls the development of cells with rooting functions in land plants. AB - Land plants develop filamentous cells-root hairs, rhizoids, and caulonemata-at the interface with the soil. Members of the group XI basic helix-loop-helix (bHLH) transcription factors encoded by LOTUS JAPONICUS ROOTHAIRLESS1-LIKE (LRL) genes positively regulate the development of root hairs in the angiosperms Lotus japonicus, Arabidopsis thaliana, and rice (Oryza sativa). Here we show that auxin promotes rhizoid and caulonema development by positively regulating the expression of PpLRL1 and PpLRL2, the two LRL genes in the Physcomitrella patens genome. Although the group VIII bHLH proteins, AtROOT HAIR DEFECTIVE6 and AtROOT HAIR DEFECTIVE SIX-LIKE1, promote root-hair development by positively regulating the expression of AtLRL3 in A. thaliana, LRL genes promote rhizoid development independently of PpROOT HAIR DEFECTIVE SIX-LIKE1 and PpROOT HAIR DEFECITVE SIX LIKE2 (PpRSL1 and PpRSL2) gene function in P. patens. Together, these data demonstrate that both LRL and RSL genes are components of an ancient auxin regulated gene network that controls the development of tip-growing cells with rooting functions among most extant land plants. Although this network has diverged in the moss and the angiosperm lineages, our data demonstrate that the core network acted in the last common ancestor of the mosses and angiosperms that existed sometime before 420 million years ago. PMID- 26150510 TI - Statistical energy conservation principle for inhomogeneous turbulent dynamical systems. AB - Understanding the complexity of anisotropic turbulent processes over a wide range of spatiotemporal scales in engineering shear turbulence as well as climate atmosphere ocean science is a grand challenge of contemporary science with important societal impact. In such inhomogeneous turbulent dynamical systems there is a large dimensional phase space with a large dimension of unstable directions where a large-scale ensemble mean and the turbulent fluctuations exchange energy and strongly influence each other. These complex features strongly impact practical prediction and uncertainty quantification. A systematic energy conservation principle is developed here in a Theorem that precisely accounts for the statistical energy exchange between the mean flow and the related turbulent fluctuations. This statistical energy is a sum of the energy in the mean and the trace of the covariance of the fluctuating turbulence. This result applies to general inhomogeneous turbulent dynamical systems including the above applications. The Theorem involves an assessment of statistical symmetries for the nonlinear interactions and a self-contained treatment is presented below. Corollary 1 and Corollary 2 illustrate the power of the method with general closed differential equalities for the statistical energy in time either exactly or with upper and lower bounds, provided that the negative symmetric dissipation matrix is diagonal in a suitable basis. Implications of the energy principle for low-order closure modeling and automatic estimates for the single point variance are discussed below. PMID- 26150512 TI - Correction for Zhou et al., NPAS3 is a trachealess homolog critical for lung development and homeostasis. PMID- 26150513 TI - Multiple accounts of adolescent impulsivity. PMID- 26150511 TI - Molecular basis for the specific recognition of the metazoan cyclic GMP-AMP by the innate immune adaptor protein STING. AB - Cyclic GMP-AMP containing a unique combination of mixed phosphodiester linkages (2'3'-cGAMP) is an endogenous second messenger molecule that activates the type-I IFN pathway upon binding to the homodimer of the adaptor protein STING on the surface of endoplasmic reticulum membrane. However, the preferential binding of the asymmetric ligand 2'3'-cGAMP to the symmetric dimer of STING represents a physicochemical enigma. Here we show that 2'3'-cGAMP, but not its linkage isomers, adopts an organized free-ligand conformation that resembles the STING bound conformation and pays low entropy and enthalpy costs in converting into the active conformation. Our results demonstrate that analyses of free-ligand conformations can be as important as analyses of protein conformations in understanding protein-ligand interactions. PMID- 26150514 TI - Spectrum of power laws for curved hand movements. AB - In a planar free-hand drawing of an ellipse, the speed of movement is proportional to the -1/3 power of the local curvature, which is widely thought to hold for general curved shapes. We investigated this phenomenon for general curved hand movements by analyzing an optimal control model that maximizes a smoothness cost and exhibits the -1/3 power for ellipses. For the analysis, we introduced a new representation for curved movements based on a moving reference frame and a dimensionless angle coordinate that revealed scale-invariant features of curved movements. The analysis confirmed the power law for drawing ellipses but also predicted a spectrum of power laws with exponents ranging between 0 and 2/3 for simple movements that can be characterized by a single angular frequency. Moreover, it predicted mixtures of power laws for more complex, multifrequency movements that were confirmed with human drawing experiments. The speed profiles of arbitrary doodling movements that exhibit broadband curvature profiles were accurately predicted as well. These findings have implications for motor planning and predict that movements only depend on one radian of angle coordinate in the past and only need to be planned one radian ahead. PMID- 26150515 TI - New method to compute Rcomplete enables maximum likelihood refinement for small datasets. AB - The crystallographic reliability index [Formula: see text] is based on a method proposed more than two decades ago. Because its calculation is computationally expensive its use did not spread into the crystallographic community in favor of the cross-validation method known as [Formula: see text]. The importance of [Formula: see text] has grown beyond a pure validation tool. However, its application requires a sufficiently large dataset. In this work we assess the reliability of [Formula: see text] and we compare it with k-fold cross validation, bootstrapping, and jackknifing. As opposed to proper cross-validation as realized with [Formula: see text], [Formula: see text] relies on a method of reducing bias from the structural model. We compare two different methods reducing model bias and question the widely spread notion that random parameter shifts are required for this purpose. We show that [Formula: see text] has as little statistical bias as [Formula: see text] with the benefit of a much smaller variance. Because the calculation of [Formula: see text] is based on the entire dataset instead of a small subset, it allows the estimation of maximum likelihood parameters even for small datasets. [Formula: see text] enables maximum likelihood-based refinement to be extended to virtually all areas of crystallographic structure determination including high-pressure studies, neutron diffraction studies, and datasets from free electron lasers. PMID- 26150516 TI - Superresolution fluorescence mapping of single-nanoparticle catalysts reveals spatiotemporal variations in surface reactivity. AB - For the practical application of nanocatalysts, it is desirable to understand the spatiotemporal fluctuations of nanocatalytic activity at the single-nanoparticle level. Here we use time-lapsed superresolution mapping of single-molecule catalysis events on individual nanoparticles to observe time-varying changes in the spatial distribution of catalysis events on Sb-doped TiO2 nanorods and Au triangle nanoplates. Compared with the active sites on well-defined surface facets, the defects of the nanoparticle catalysts possess higher intrinsic reactivity but lower stability. Corners and ends are more reactive but also less stable than flat surfaces. Averaged over time, the most stable sites dominate the total apparent activity of single nanocatalysts. However, the active sites with higher intrinsic activity but lower stability show activity at earlier time points before deactivating. Unexpectedly, some active sites are found to recover their activity ("self-healing") after deactivation, which is probably due to desorption of the adsorbate. Our superresolution measurement of different types of active catalytic sites, over both space and time, leads to a more comprehensive understanding of reactivity patterns and may enable the design of new and more productive heterogeneous catalysts. PMID- 26150518 TI - Stochastic game dynamics under demographic fluctuations. AB - Frequency-dependent selection and demographic fluctuations play important roles in evolutionary and ecological processes. Under frequency-dependent selection, the average fitness of the population may increase or decrease based on interactions between individuals within the population. This should be reflected in fluctuations of the population size even in constant environments. Here, we propose a stochastic model that naturally combines these two evolutionary ingredients by assuming frequency-dependent competition between different types in an individual-based model. In contrast to previous game theoretic models, the carrying capacity of the population, and thus the population size, is determined by pairwise competition of individuals mediated by evolutionary games and demographic stochasticity. In the limit of infinite population size, the averaged stochastic dynamics is captured by deterministic competitive Lotka-Volterra equations. In small populations, demographic stochasticity may instead lead to the extinction of the entire population. Because the population size is driven by fitness in evolutionary games, a population of cooperators is less prone to go extinct than a population of defectors, whereas in the usual systems of fixed size the population would thrive regardless of its average payoff. PMID- 26150517 TI - ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis. AB - Mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the liver removes toxic aldehydes including acetaldehyde, an intermediate of ethanol metabolism. Nearly 40% of East Asians inherit an inactive ALDH2*2 variant, which has a lysine-for glutamate substitution at position 487 (E487K), and show a characteristic alcohol flush reaction after drinking and a higher risk for gastrointestinal cancers. Here we report the characterization of knockin mice in which the ALDH2(E487K) mutation is inserted into the endogenous murine Aldh2 locus. These mutants recapitulate essentially all human phenotypes including impaired clearance of acetaldehyde, increased sensitivity to acute or chronic alcohol-induced toxicity, and reduced ALDH2 expression due to a dominant-negative effect of the mutation. When treated with a chemical carcinogen, these mutants exhibit increased DNA damage response in hepatocytes, pronounced liver injury, and accelerated development of hepatocellular carcinoma (HCC). Importantly, ALDH2 protein levels are also significantly lower in patient HCC than in peritumor or normal liver tissues. Our results reveal that ALDH2 functions as a tumor suppressor by maintaining genomic stability in the liver, and the common human ALDH2 variant would present a significant risk factor for hepatocarcinogenesis. Our study suggests that the ALDH2*2 allele-alcohol interaction may be an even greater human public health hazard than previously appreciated. PMID- 26150519 TI - Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia. AB - Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population. PMID- 26150521 TI - Climatic controls on ecosystem resilience: Postfire regeneration in the Cape Floristic Region of South Africa. AB - Conservation of biodiversity and natural resources in a changing climate requires understanding what controls ecosystem resilience to disturbance. This understanding is especially important in the fire-prone Mediterranean systems of the world. The fire frequency in these systems is sensitive to climate, and recent climate change has resulted in more frequent fires over the last few decades. However, the sensitivity of postfire recovery and biomass/fuel load accumulation to climate is less well understood than fire frequency despite its importance in driving the fire regime. In this study, we develop a hierarchical statistical framework to model postfire ecosystem recovery using satellite derived observations of vegetation as a function of stand age, topography, and climate. In the Cape Floristic Region (CFR) of South Africa, a fire-prone biodiversity hotspot, we found strong postfire recovery gradients associated with climate resulting in faster recovery in regions with higher soil fertility, minimum July (winter) temperature, and mean January (summer) precipitation. Projections using an ensemble of 11 downscaled Coupled Model Intercomparison Project Phase 5 (CMIP5) general circulation models (GCMs) suggest that warmer winter temperatures in 2080-2100 will encourage faster postfire recovery across the region, which could further increase fire frequency due to faster fuel accumulation. However, some models project decreasing precipitation in the western CFR, which would slow recovery rates there, likely reducing fire frequency through lack of fuel and potentially driving local biome shifts from fynbos shrubland to nonburning semidesert vegetation. This simple yet powerful approach to making inferences from large, remotely sensed datasets has potential for wide application to modeling ecosystem resilience in disturbance-prone ecosystems globally. PMID- 26150520 TI - Structure of a herpesvirus nuclear egress complex subunit reveals an interaction groove that is essential for viral replication. AB - Herpesviruses require a nuclear egress complex (NEC) for efficient transit of nucleocapsids from the nucleus to the cytoplasm. The NEC orchestrates multiple steps during herpesvirus nuclear egress, including disruption of nuclear lamina and particle budding through the inner nuclear membrane. In the important human pathogen human cytomegalovirus (HCMV), this complex consists of nuclear membrane protein UL50, and nucleoplasmic protein UL53, which is recruited to the nuclear membrane through its interaction with UL50. Here, we present an NMR-determined solution-state structure of the murine CMV homolog of UL50 (M50; residues 1-168) with a strikingly intricate protein fold that is matched by no other known protein folds in its entirety. Using NMR methods, we mapped the interaction of M50 with a highly conserved UL53-derived peptide, corresponding to a segment that is required for heterodimerization. The UL53 peptide binding site mapped onto an M50 surface groove, which harbors a large cavity. Point mutations of UL50 residues corresponding to surface residues in the characterized M50 heterodimerization interface substantially decreased UL50-UL53 binding in vitro, eliminated UL50-UL53 colocalization, prevented disruption of nuclear lamina, and halted productive virus replication in HCMV-infected cells. Our results provide detailed structural information on a key protein-protein interaction involved in nuclear egress and suggest that NEC subunit interactions can be an attractive drug target. PMID- 26150522 TI - Behavioral consequences of selective damage to frontal pole and posterior cingulate cortices. AB - Frontal pole cortex (FPC) and posterior cingulate cortex (PCC) have close neuroanatomical connections, and imaging studies have shown coactivation or codeactivation of these brain regions during performance of certain tasks. However, they are among the least well-understood regions of the primate brain. One reason for this is that the consequences of selective bilateral lesions to either structure have not previously been studied in any primate species. We studied the effects of circumscribed bilateral lesions to FPC or PCC on monkeys' ability to perform an analog of Wisconsin Card Sorting Test (WCST) and related tasks. In contrast to lesions in other prefrontal regions, neither posttraining FPC nor PCC lesions impaired animals' abilities to follow the rule switches that frequently occurred within the WCST task. However, FPC lesions were not without effect, because they augmented the ability of animals to adjust cognitive control after experiencing high levels of conflict (whereas PCC lesions did not have any effect). In addition, FPC-lesioned monkeys were more successful than controls or PCC-lesioned animals at remembering the relevant rule across experimentally imposed distractions involving either an intervening secondary task or a surprising delivery of free reward. Although prefrontal cortex posterior to FPC is specialized for mediating efficient goal-directed behavior to maximally exploit reward opportunities from ongoing tasks, our data led us to suggest that FPC is, instead, specialized for disengaging executive control from the current task and redistributing it to novel sources of reward to explore new opportunities/goals. PMID- 26150524 TI - QnAs with Venki Ramakrishnan. PMID- 26150523 TI - Structure and mechanism of the ATPase that powers viral genome packaging. AB - Many viruses package their genomes into procapsids using an ATPase machine that is among the most powerful known biological motors. However, how this motor couples ATP hydrolysis to DNA translocation is still unknown. Here, we introduce a model system with unique properties for studying motor structure and mechanism. We describe crystal structures of the packaging motor ATPase domain that exhibit nucleotide-dependent conformational changes involving a large rotation of an entire subdomain. We also identify the arginine finger residue that catalyzes ATP hydrolysis in a neighboring motor subunit, illustrating that previous models for motor structure need revision. Our findings allow us to derive a structural model for the motor ring, which we validate using small-angle X-ray scattering and comparisons with previously published data. We illustrate the model's predictive power by identifying the motor's DNA-binding and assembly motifs. Finally, we integrate our results to propose a mechanistic model for DNA translocation by this molecular machine. PMID- 26150525 TI - Dynamics of change in multiethnic societies. PMID- 26150527 TI - Tracing the ingredients for a habitable earth from interstellar space through planet formation. AB - We use the C/N ratio as a monitor of the delivery of key ingredients of life to nascent terrestrial worlds. Total elemental C and N contents, and their ratio, are examined for the interstellar medium, comets, chondritic meteorites, and terrestrial planets; we include an updated estimate for the bulk silicate Earth (C/N = 49.0 +/- 9.3). Using a kinetic model of disk chemistry, and the sublimation/condensation temperatures of primitive molecules, we suggest that organic ices and macromolecular (refractory or carbonaceous dust) organic material are the likely initial C and N carriers. Chemical reactions in the disk can produce nebular C/N ratios of ~1-12, comparable to those of comets and the low end estimated for planetesimals. An increase of the C/N ratio is traced between volatile-rich pristine bodies and larger volatile-depleted objects subjected to thermal/accretional metamorphism. The C/N ratios of the dominant materials accreted to terrestrial planets should therefore be higher than those seen in carbonaceous chondrites or comets. During planetary formation, we explore scenarios leading to further volatile loss and associated C/N variations owing to core formation and atmospheric escape. Key processes include relative enrichment of nitrogen in the atmosphere and preferential sequestration of carbon by the core. The high C/N bulk silicate Earth ratio therefore is best satisfied by accretion of thermally processed objects followed by large-scale atmospheric loss. These two effects must be more profound if volatile sequestration in the core is effective. The stochastic nature of these processes hints that the surface/atmospheric abundances of biosphere-essential materials will likely be variable. PMID- 26150526 TI - EGFR inhibition evokes innate drug resistance in lung cancer cells by preventing Akt activity and thus inactivating Ets-1 function. AB - Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. About 14% of NSCLCs harbor mutations in epidermal growth factor receptor (EGFR). Despite remarkable progress in treatment with tyrosine kinase inhibitors (TKIs), only 5% of patients achieve tumor reduction >90%. The limited primary responses are attributed partly to drug resistance inherent in the tumor cells before therapy begins. Recent reports showed that activation of receptor tyrosine kinases (RTKs) is an important determinant of this innate drug resistance. In contrast, we demonstrate that EGFR inhibition promotes innate drug resistance despite blockade of RTK activity in NSCLC cells. EGFR TKIs decrease both the mitogen-activated protein kinase (MAPK) and Akt protein kinase pathways for a short time, after which the Ras/MAPK pathway becomes reactivated. Akt inhibition selectively blocks the transcriptional activation of Ets-1, which inhibits its target gene, dual specificity phosphatase 6 (DUSP6), a negative regulator specific for ERK1/2. As a result, ERK1/2 is activated. Furthermore, elevated c Src stimulates Ras GTP-loading and activates Raf and MEK kinases. These observations suggest that not only ERK1/2 but also Akt activity is essential to maintain Ets-1 in an active state. Therefore, despite high levels of ERK1/2, Ets 1 target genes including DUSP6 and cyclins D1, D3, and E2 remain suppressed by Akt inhibition. Reduction of DUSP6 in combination with elevated c-Src renews activation of the Ras/MAPK pathway, which enhances cell survival by accelerating Bim protein turnover. Thus, EGFR TKIs evoke innate drug resistance by preventing Akt activity and inactivating Ets-1 function in NSCLC cells. PMID- 26150528 TI - Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly. AB - The rod of sarcomeric myosins directs thick filament assembly and is characterized by the insertion of four skip residues that introduce discontinuities in the coiled-coil heptad repeats. We report here that the regions surrounding the first three skip residues share high structural similarity despite their low sequence homology. Near each of these skip residues, the coiled-coil transitions to a nonclose-packed structure inducing local relaxation of the superhelical pitch. Moreover, molecular dynamics suggest that these distorted regions can assume different conformationally stable states. In contrast, the last skip residue region constitutes a true molecular hinge, providing C-terminal rod flexibility. Assembly of myosin with mutated skip residues in cardiomyocytes shows that the functional importance of each skip residue is associated with rod position and reveals the unique role of the molecular hinge in promoting myosin antiparallel packing. By defining the biophysical properties of the rod, the structures and molecular dynamic calculations presented here provide insight into thick filament formation, and highlight the structural differences occurring between the coiled-coils of myosin and the stereotypical tropomyosin. In addition to extending our knowledge into the conformational and biological properties of coiled-coil discontinuities, the molecular characterization of the four myosin skip residues also provides a guide to modeling the effects of rod mutations causing cardiac and skeletal myopathies. PMID- 26150530 TI - Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells. AB - Adenosine receptor-mediated regulation of monocyte/macrophage inflammatory responses is critical in the maintenance of tissue homeostasis. In this study, we reveal that adenosine potently modulates the expression of NR4A1, 2, and 3 orphan nuclear receptors in myeloid cells, and this modulation is primarily through the adenosine A2a receptor subtype. We demonstrate that A2a receptor activation of NR4A1-3 receptor synthesis is further enhanced in TLR4-stimulated monocytes. After TLR4 stimulation, NR4A receptor-depleted monocyte/macrophage cells display significantly altered expression of cell-surface markers and produce increased inflammatory cytokine and chemokine secretion rendering the cells an enhanced proinflammatory phenotype. Exposure of TLR4 or TNF-alpha-stimulated monocytes to adenosine analogs directs changes in the expression of MIP-3alpha and IL-23p19, with NR4A2 depletion leading to significantly enhanced expression of these factors. Furthermore, we establish that nuclear levels of NF-kappaB/p65 are increased in TLR/adenosine-stimulated NR4A2-depleted cells. We show that, after TLR/adenosine receptor stimulation, NR4A2 depletion promotes significant binding of NF-kappaB/p65 to a kappaB consensus binding motif within the MIP-3alpha proximal promoter leading to increased protein secretion, confirming a pivotal role for NF-kappaB activity in controlling cellular responses and gene expression outcomes in response to these mediators. Thus, these data demonstrate that during an inflammatory response, adenosine modulation of NR4A receptor activity acts to limit NF-kappaB-mediated effects and that loss of NR4A2 expression leads to enhanced NF-kappaB activity and hyperinflammatory responses in myeloid cells. PMID- 26150529 TI - Antigenic Stimulation of Kv1.3-Deficient Th Cells Gives Rise to a Population of Foxp3-Independent T Cells with Suppressive Properties. AB - Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS that has been linked with defects in regulatory T cell function. Therefore, strategies to selectively target pathogenic cells via enhanced regulatory T cell activity may provide therapeutic benefit. Kv1.3 is a voltage-gated potassium channel expressed on myelin-reactive T cells from MS patients. Kv1.3-knockout (KO) mice are protected from experimental autoimmune encephalomyelitis, an animal model of MS, and Kv1.3-KO Th cells display suppressive capacity associated with increased IL-10. In this article, we demonstrate that myelin oligodendrocyte glycoprotein-specific Kv1.3-KO Th cells exhibit a unique regulatory phenotype characterized by high CD25, CTLA4, pSTAT5, FoxO1, and GATA1 expression without a corresponding increase in Foxp3. These phenotypic changes result from increased signaling through IL-2R. Moreover, myelin oligodendrocyte glycoprotein-specific Kv1.3-KO Th cells can ameliorate experimental autoimmune encephalomyelitis following transfer to wild-type recipients in a manner that is partially dependent on IL-2R and STAT5 signaling. The present study identifies a population of Foxp3(-) T cells with suppressive properties that arises in the absence of Kv1.3 and enhances the understanding of the molecular mechanism by which these cells are generated. This increased understanding could contribute to the development of novel therapies for MS patients that promote heightened immune regulation. PMID- 26150531 TI - VprBP Is Required for Efficient Editing and Selection of Igkappa+ B Cells, but Is Dispensable for Iglambda+ and Marginal Zone B Cell Maturation and Selection. AB - B cell development past the pro-B cell stage in mice requires the Cul4-Roc1-DDB1 E3 ubiquitin ligase substrate recognition subunit VprBP. Enforced Bcl2 expression overcomes defects in distal VH-DJH and secondary Vkappa-Jkappa rearrangement associated with VprBP insufficiency in B cells and substantially rescues maturation of marginal zone and Iglambda(+) B cells, but not Igkappa(+) B cells. In this background, expression of a site-directed Igkappa L chain transgene increases Igkappa(+) B cell frequency, suggesting VprBP does not regulate L chain expression from a productively rearranged Igk allele. In site-directed anti-dsDNA H chain transgenic mice, loss of VprBP function in B cells impairs selection of Igkappa editor L chains typically arising through secondary Igk rearrangement, but not selection of Iglambda editor L chains. Both H and L chain site-directed transgenic mice show increased B cell anergy when VprBP is inactivated in B cells. Taken together, these data argue that VprBP is required for the efficient receptor editing and selection of Igkappa(+) B cells, but is largely dispensable for Iglambda(+) B cell development and selection, and that VprBP is necessary to rescue autoreactive B cells from anergy induction. PMID- 26150532 TI - The B Cell-Stimulatory Cytokines BLyS and APRIL Are Elevated in Human Periodontitis and Are Required for B Cell-Dependent Bone Loss in Experimental Murine Periodontitis. AB - B-lineage cells (B lymphocytes and plasma cells) predominate in the inflammatory infiltrate of human chronic periodontitis. However, their role in disease pathogenesis and the factors responsible for their persistence in chronic lesions are poorly understood. In this regard, two cytokines of the TNF ligand superfamily, a proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), are important for the survival, proliferation, and maturation of B cells. Thus, we hypothesized that APRIL and/or BLyS are upregulated in periodontitis and contribute to induction of periodontal bone loss. This hypothesis was addressed in both human and mouse experimental systems. We show that, relative to healthy controls, the expression of APRIL and BLyS mRNA and protein was upregulated in natural and experimental periodontitis in humans and mice, respectively. The elevated expression of these cytokines correlated with increased numbers of B cells/plasma cells in both species. Moreover, APRIL and BLyS partially colocalized with kappa L chain-expressing B-lineage cells at the epithelial connective tissue interface. Ligature-induced periodontitis resulted in significantly less bone loss in B cell-deficient mice compared with wild-type controls. Ab-mediated neutralization of APRIL or BLyS diminished the number of B cells in the gingival tissue and inhibited bone loss in wild-type, but not in B cell-deficient, mice. In conclusion, B cells and specific cytokines involved in their growth and differentiation contribute to periodontal bone loss. Moreover, APRIL and BLyS have been identified as potential therapeutic targets in periodontitis. PMID- 26150533 TI - Circulating Human CD27-IgA+ Memory B Cells Recognize Bacteria with Polyreactive Igs. AB - The vast majority of IgA production occurs in mucosal tissue following T cell dependent and T cell-independent Ag responses. To study the nature of each of these responses, we analyzed the gene-expression and Ig-reactivity profiles of T cell-dependent CD27(+)IgA(+) and T cell-independent CD27(-)IgA(+) circulating memory B cells. Gene-expression profiles of IgA(+) subsets were highly similar to each other and to IgG(+) memory B cell subsets, with typical upregulation of activation markers and downregulation of inhibitory receptors. However, we identified the mucosa-associated CCR9 and RUNX2 genes to be specifically upregulated in CD27(-)IgA(+) B cells. We also found that CD27(-)IgA(+) B cells expressed Abs with distinct Ig repertoire and reactivity compared with those from CD27(+)IgA(+) B cells. Indeed, Abs from CD27(-)IgA(+) B cells were weakly mutated, often used Iglambda chain, and were enriched in polyreactive clones recognizing various bacterial species. Hence, T cell-independent IgA responses are likely involved in the maintenance of gut homeostasis through the production of polyreactive mutated IgA Abs with cross-reactive anti-commensal reactivity. PMID- 26150535 TI - Ecto-5'-Nucleotidase (CD73) Deficiency in Mycobacterium tuberculosis-Infected Mice Enhances Neutrophil Recruitment. AB - The immune system needs safeguards that prevent collateral tissue damage mediated by the immune system while enabling an effective response against a pathogen. The purinergic pathway is one such mechanism and finely modulates inflammation by sensing nucleotides in the environment. Extracellular ATP is considered to be a danger signal leading to a proinflammatory response, whereas adenosine is immunosuppressive. CD73, also called ecto-5'-nucleotidase, occupies a strategic position in this pathway, as it is the main enzyme responsible for the generation of adenosine from ATP. Here, we explore the role of CD73 during tuberculosis, a disease characterized by an immune response that is harmful to the host and unable to eradicate Mycobacterium tuberculosis. Using CD73 knockout (KO) mice, we found that CD73 regulates the response to M. tuberculosis infection in vitro and in vivo. Mycobacterium-infected murine macrophages derived from CD73 KO mice secrete more keratinocyte chemoattractant (KC), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) and release less vascular endothelial growth factor (VEGF) upon ATP stimulation than do those derived from wild-type (WT) mice. In vivo, CD73 limits the early influx of neutrophils to the lungs without affecting bacterial growth and dissemination. Collectively, our results support the view that CD73 fine-tunes antimycobacterial immune responses. PMID- 26150534 TI - BB0744 Affects Tissue Tropism and Spatial Distribution of Borrelia burgdorferi. AB - Borrelia burgdorferi, the etiologic agent of Lyme disease, produces a variety of proteins that promote survival and colonization in both the Ixodes species vector and various mammalian hosts. We initially identified BB0744 (also known as p83/100) by screening for B. burgdorferi strain B31 proteins that bind to alpha1beta1 integrin and hypothesized that, given the presence of a signal peptide, BB0744 may be a surface-exposed protein. In contrast to this expectation, localization studies suggested that BB0744 resides in the periplasm. Despite its subsurface location, we were interested in testing whether BB0744 is required for borrelial pathogenesis. To this end, a bb0744 deletion was isolated in a B. burgdorferi strain B31 infectious background, complemented, and queried for the role of BB0744 following experimental infection. A combination of bioluminescent imaging, cultivation of infected tissues, and quantitative PCR (qPCR) demonstrated that Deltabb0744 mutant B. burgdorferi bacteria were attenuated in the ability to colonize heart tissue, as well as skin locations distal to the site of infection. Furthermore, qPCR indicated a significantly reduced spirochetal load in distal skin and joint tissue infected with Deltabb0744 mutant B. burgdorferi. Complementation with bb0744 restored infectivity, indicating that the defect seen in Deltabb0744 mutant B. burgdorferi was due to the loss of BB0744. Taken together, these results suggest that BB0744 is necessary for tissue tropism, particularly in heart tissue, alters the ability of B. burgdorferi to disseminate efficiently, or both. Additional studies are warranted to address the mechanism employed by BB0744 that alters the pathogenic potential of B. burgdorferi. PMID- 26150536 TI - Borrelia burgdorferi RevA Significantly Affects Pathogenicity and Host Response in the Mouse Model of Lyme Disease. AB - The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, with increased fibrotic collagen deposition in tibiotarsal joints. The mutants also induced increased levels of the chemokine CCL2, a monocyte chemoattractant, in serum, and this increase was abolished in the complemented strain. Therefore, while revA is not absolutely essential for infection, deletion of revA had distinct effects on dissemination, arthritis severity, and host response. PMID- 26150537 TI - A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection. AB - Candida albicans is normally a commensal fungus of the human mucosae and skin, but it causes life-threatening systemic infections in hospital settings in the face of predisposing conditions, such as indwelling catheters, abdominal surgery, or antibiotic use. Immunity to C. albicans involves various immune parameters, but the cytokine interleukin-17A (IL-17A) (also known as IL-17) has emerged as a centrally important mediator of immune defense against both mucosal and systemic candidiasis. Conversely, IL-17A has been suggested to enhance the virulence of C. albicans, indicating that it may exert detrimental effects on pathogenesis. In this study, we hypothesized that a C. albicans strain expressing IL-17A would exhibit reduced virulence in vivo. To that end, we created a Candida-optimized expression cassette encoding murine IL-17A, which was transformed into the DAY286 strain of C. albicans. Candida-derived IL-17A was indistinguishable from murine IL-17A in terms of biological activity and detection in standard enzyme-linked immunosorbent assays (ELISAs). Expression of IL-17A did not negatively impact the growth of these strains in vitro. Moreover, the IL-17A-expressing C. albicans strains showed significantly reduced pathogenicity in a systemic model of Candida infection, mainly evident during the early stages of disease. Collectively, these findings suggest that IL-17A mitigates the virulence of C. albicans. PMID- 26150538 TI - Parasite Proximity Drives the Expansion of Regulatory T Cells in Peyer's Patches following Intestinal Helminth Infection. AB - Helminth infections are typically chronic in nature; however, the exact molecular mechanisms by which these parasites promote or thwart host immunity remain unclear. Worm expulsion requires the differentiation of CD4(+) T cells into Th2 cells, while regulatory T cells (Tregs) act to dampen the extent of the Th2 response. Priming of T cells requires drainage or capture of antigens within lymphoid tissues, and in the case of intestinal helminths, such sites include the mucosa-associated Peyer's patches (PPs) and the draining mesenteric lymph nodes (MLN). To gain insight into when and where the activation of the adaptive T cell response takes place following intestinal helminth infection, we analyzed Th2 and Treg responses in the PPs and MLN following infection with the murine intestinal helminth Heligmosomoides polygyrus bakeri. Protective Th2 responses were observed to be largely restricted to the MLN, while a greater expansion of Tregs occurred within the PPs. Interestingly, those PPs that formed a contact with the parasite showed the greatest degree of Treg expansion and no evidence of type 2 cytokine production, indicating that the parasite may secrete products that act in a local manner to selectively promote Treg expansion. This view was supported by the finding that H. polygyrus bakeri larvae could promote Treg proliferation in vitro. Taken together, these data indicate that different degrees of Treg expansion and type 2 cytokine production occur within the PPs and MLN following infection with the intestinal helminth H. polygyrus bakeri and indicate that these organs exhibit differential responses following infection with intestinal helminths. PMID- 26150539 TI - Evaluation of the Role of the opgGH Operon in Yersinia pseudotuberculosis and Its Deletion during the Emergence of Yersinia pestis. AB - The opgGH operon encodes glucosyltransferases that synthesize osmoregulated periplasmic glucans (OPGs) from UDP-glucose, using acyl carrier protein (ACP) as a cofactor. OPGs are required for motility, biofilm formation, and virulence in various bacteria. OpgH also sequesters FtsZ in order to regulate cell size according to nutrient availability. Yersinia pestis (the agent of flea-borne plague) lost the opgGH operon during its emergence from the enteropathogen Yersinia pseudotuberculosis. When expressed in OPG-negative strains of Escherichia coli and Dickeya dadantii, opgGH from Y. pseudotuberculosis restored OPGs synthesis, motility, and virulence. However, Y. pseudotuberculosis did not produce OPGs (i) under various growth conditions or (ii) when overexpressing its opgGH operon, its galUF operon (governing UDP-glucose), or the opgGH operon or Acp from E. coli. A DeltaopgGH Y. pseudotuberculosis strain showed normal motility, biofilm formation, resistance to polymyxin and macrophages, and virulence but was smaller. Consistently, Y. pestis was smaller than Y. pseudotuberculosis when cultured at >= 37 degrees C, except when the plague bacillus expressed opgGH. Y. pestis expressing opgGH grew normally in serum and within macrophages and was fully virulent in mice, suggesting that small cell size was not advantageous in the mammalian host. Lastly, Y. pestis expressing opgGH was able to infect Xenopsylla cheopis fleas normally. Our results suggest an evolutionary scenario whereby an ancestral Yersinia strain lost a factor required for OPG biosynthesis but kept opgGH (to regulate cell size). The opgGH operon was presumably then lost because OpgH-dependent cell size control became unnecessary. PMID- 26150540 TI - The Genotoxin Colibactin Is a Determinant of Virulence in Escherichia coli K1 Experimental Neonatal Systemic Infection. AB - Escherichia coli strains expressing the K1 capsule are a major cause of sepsis and meningitis in human neonates. The development of these diseases is dependent on the expression of a range of virulence factors, many of which remain uncharacterized. Here, we show that all but 1 of 34 E. coli K1 neonatal isolates carried clbA and clbP, genes contained within the pks pathogenicity island and required for the synthesis of colibactin, a polyketide-peptide genotoxin that causes genomic instability in eukaryotic cells by induction of double-strand breaks in DNA. Inactivation of clbA and clbP in E. coli A192PP, a virulent strain of serotype O18:K1 that colonizes the gastrointestinal tract and translocates to the blood compartment with very high frequency in experimental infection of the neonatal rat, significantly reduced the capacity of A192PP to colonize the gut, engender double-strand breaks in DNA, and cause invasive, lethal disease. Mutation of clbA, which encodes a pleiotropic enzyme also involved in siderophore synthesis, impacted virulence to a greater extent than mutation of clbP, encoding an enzyme specific to colibactin synthesis. Restoration of colibactin gene function by complementation reestablished the fully virulent phenotype. We conclude that colibactin contributes to the capacity of E. coli K1 to colonize the neonatal gastrointestinal tract and to cause invasive disease in the susceptible neonate. PMID- 26150541 TI - Heparan Sulfate Modulates Neutrophil and Endothelial Function in Antibacterial Innate Immunity. AB - Recently, we showed that endothelial heparan sulfate facilitates entry of a bacterial pathogen into the central nervous system. Here, we show that normal bactericidal activity of neutrophils is influenced by the sulfation pattern of heparan sulfate. Inactivation of heparan sulfate uronyl 2-O-sulfotransferase (Hs2st) in neutrophils substantially reduced their bactericidal activity, and Hs2st deficiency rendered mice more susceptible to systemic infection with the pathogenic bacterium group B Streptococcus. Specifically, altered sulfation of heparan sulfate in mutant neutrophils affected formation of neutrophil extracellular traps while not influencing phagocytosis, production of reactive oxygen species, or secretion of granular proteases. Heparan sulfate proteoglycan(s) is present in neutrophil extracellular traps, modulates histone affinity, and modulates their microbial activity. Hs2st-deficient brain endothelial cells show enhanced binding to group B Streptococcus and are more susceptible to apoptosis, likely contributing to the observed increase in dissemination of group B Streptococcus into the brain of Hs2st-deficient mice following intravenous challenge. Taken together, our data provide strong evidence that heparan sulfate from both neutrophils and the endothelium plays important roles in modulating innate immunity. PMID- 26150542 TI - Fetal Endothelial Remodeling in Late-Onset Gestational Hypertension. AB - BACKGROUND: Recent studies reveal that offspring of pregnancies complicated by hypertensive disorders may have an increased cardiovascular risk. Genetic and nongenetic factors seem to play an important role in premature arterial disease. Endothelium may be significant for long-term remodeling of the arterial wall. The aim of the study was to assess fetal endothelial and renal function in late-onset gestational hypertension. MATERIALS AND METHODS: This was a case-controlled study. Singleton pregnancies affected by late-onset gestational hypertension (after 34 weeks' gestation) and controls were included. Ultrasound examinations (fetal biometry, fetal Doppler, fetal aorta intima media thickness (aIMT), fetal kidney volumes, maternal Doppler, presence of uterine arteries protodiastolic notching from anomaly scan) and clinical data were collected. A sample of amniotic fluid was taken at delivery. RESULTS: Fifty patients with late-onset hypertension and 50 controls were included. At growth scan (weeks 29-32) we found in the study group significantly higher fetal aIMT, umbilical artery pulsatility index (PI), fetal aorta PI, and mean uterine arteries PI with persistent bilateral notch. In the case group microalbuminuria levels were significantly higher than controls (1.32+/-0.11 vs. 1.10+/-0.13g/l, P < 0.0001), and there was a negative correlation between renal fetal volume at growth scan and amniotic microalbuminuria (r: -0.95, 95% C -0.97 to -0.90, P < 0.0001). CONCLUSIONS: Gestational hypertension should be considered as one of the adverse early risk factors that might predispose to impaired fetal cardiovascular development during intrauterine life; therefore, this study provides further evidence to better understand the origins of cardiovascular diseases. PMID- 26150543 TI - Persistence of Masked Hypertension in Chinese Patients. AB - BACKGROUND: Masked hypertension (MH) has 10-15% prevalence and carries risk similar to that of sustained hypertension, but its short-term persistence remains uncertain. METHODS: Forty-five patients with MH (mean age 52.2 years; 37.8% women) were enrolled in the placebo arm of a randomized clinical trial of Chinese medicine (NCT02156024) and followed up for 4 weeks. MH was office normotension (<140/90mm Hg) and daytime (8:00-18:00) hypertension (>=135/85mm Hg). RESULTS: At enrolment, office and daytime systolic/diastolic blood pressure (BP) averaged 129.0/80.6mm Hg and 132.9/88.9mm Hg, respectively. Daytime BP thresholds for MH were met in 5 patients (11.1%) for systolic BP, in 25 (55.6%) for diastolic BP and in 15 (33.3%) for both. At follow-up, systolic and diastolic BP had not changed compared with baseline (P >= 0.12), except for a 2.1mm Hg decrease in office systolic BP (P = 0.049). MH remained present in 28 patients (62.2%; 95% CI, 48.1-76.3%), whereas 13 (28.9%; 15.7-42.1%) and 4 (8.9%; 0.6-17.2%) converted to normotension (daytime BP <135/85mm Hg) or sustained hypertension (office BP >=140/90mm Hg), respectively. Substituting daytime by 24-hour BP, using 130/80mm Hg as threshold, produced consistent results. Systolic office BP at baseline independently predicted persistence of MH or progression to sustained hypertension at 4 weeks (odds ratio per 1 - SD increase, 3.49; 95% CI, 1.06-11.2; P = 0.04). CONCLUSIONS: The information that MH persists over 4 weeks in over two thirds of this sample of patients should inform future clinical trials and guidelines. PMID- 26150544 TI - Metabolic Dysregulation Induced in Plasmodium falciparum by Dihydroartemisinin and Other Front-Line Antimalarial Drugs. AB - Detailed information on the mode of action of antimalarial drugs can be used to improve existing drugs, identify new drug targets, and understand the basis of drug resistance. In this study we describe the use of a time-resolved, mass spectrometry (MS)-based metabolite profiling approach to map the metabolic perturbations induced by a panel of clinical antimalarial drugs and inhibitors on Plasmodium falciparum asexual blood stages. Drug-induced changes in metabolite levels in P. falciparum-infected erythrocytes were monitored over time using gas chromatography-MS and liquid chromatography-MS and changes in specific metabolic fluxes confirmed by nonstationary [(13)C]-glucose labeling. Dihydroartemisinin (DHA) was found to disrupt hemoglobin catabolism within 1 hour of exposure, resulting in a transient decrease in hemoglobin-derived peptides. Unexpectedly, it also disrupted pyrimidine biosynthesis, resulting in increased [(13)C]-glucose flux toward malate production, potentially explaining the susceptibility of P. falciparum to DHA during early blood-stage development. Unique metabolic signatures were also found for atovaquone, chloroquine, proguanil, cycloguanil and methylene blue. We also show that this approach can be used to identify the mode of action of novel antimalarials, such as the compound Torin 2, which inhibits hemoglobin catabolism. PMID- 26150545 TI - Antibody Signatures Reflect Different Disease Pathologies in Patients With Schistosomiasis Due to Schistosoma japonicum. AB - Infection with Schistosoma japonicum causes high levels of pathology that is predominantly determined by the cellular and humoral response of the host. However, the specific antibody response that arises during the development of disease is largely undescribed in Asian schistosomiasis-endemic populations. A schistosome protein microarray was used to compare the antibody profiles of subjects with acute infection, with early or advanced disease associated with severe pathology, with chronic infection, and subjects exposed but stool negative for S. japonicum eggs to the antibody profiles of nonexposed controls. Twenty five immunodominant antigens were identified, including vaccine candidates, tetraspanin-related proteins, transporter molecules, and unannotated proteins. Additionally, individuals with severe pathology had a limited specific antibody response, suggesting that individuals with mild disease may use a broad and strong antibody response, particularly against surface-exposed proteins, to control pathology and/or infection. Our study has identified specific antigens that can discriminate between S. japonicum-exposed groups with different pathologies and may also allow the host to control disease pathology and provide resistance to parasite infection. PMID- 26150547 TI - Safety in healthcare is a moving target. PMID- 26150546 TI - Mitochondrial Dysfunction, Depleted Purinergic Signaling, and Defective T Cell Vigilance and Immune Defense. AB - T cell suppression in sepsis is a well-known phenomenon; however, the underlying mechanisms are not fully understood. Previous studies have shown that T cell stimulation up-regulates mitochondrial adenosine triphosphate (ATP) production to fuel purinergic signaling mechanisms necessary for adequate T cell responses. Here we show that basal mitochondrial ATP production, ATP release, and stimulation of P2X1 receptors represent a standby purinergic signaling mechanism that is necessary for antigen recognition. Inhibition of this process impairs T cell vigilance and the ability of T cells to trigger T cell activation, up regulate mitochondrial ATP production, and stimulate P2X4 and P2X7 receptors that elicit interleukin 2 production and T cell proliferation. T cells of patients with sepsis lack this standby purinergic signaling system owing to defects in mitochondrial function, ATP release, and calcium signaling. These defects impair antigen recognition and T cell function and are correlated with sepsis severity. Pharmacological targeting of these defects may improve T cell function and reduce the risk of sepsis. PMID- 26150548 TI - How effective are patient safety initiatives? A retrospective patient record review study of changes to patient safety over time. AB - OBJECTIVES: To assess whether, compared with previous years, hospital care became safer in 2011/2012, expressing itself in a fall in preventable adverse event (AE) rates alongside patient safety initiatives. DESIGN: Retrospective patient record review at three points in time. SETTING: In three national AE studies, patient records of 2004, 2008 and 2011/2012 were reviewed in, respectively, 21 hospitals in 2004, 20 hospitals in 2008 and 20 hospitals in 2011/2012. In each hospital, 400, 200 and 200 patient records were sampled, respectively. PARTICIPANTS: In total, 15 997 patient admissions were included in the study, 7926 patient admissions from 2004, 4023 from 2008 and 4048 from 2011/2012. INTERVENTIONS: The main patient safety initiatives in hospital care at a national level between 2004 and 2012 have been small as well as large-scale multifaceted programmes. MAIN OUTCOME MEASURES: Rates of both AEs and preventable AEs. RESULTS: Uncorrected crude overall AE rates showed no change in 2011/2012 in comparison with 2008, whereas preventable AE rates showed a reduction of 45%. After multilevel corrections, the decrease in preventable AE rate in 2011/2012 was still clearly visible with a decrease of 30% in comparison to 2008 (p=0.10). In 2011/2012, fewer preventable AEs were found in older age groups, or related to the surgical process, in comparison with 2008. CONCLUSIONS: Our study shows some improvements in preventable AEs in the areas that were addressed during the comprehensive national safety programme. There are signs that such a programme has a positive impact on patient safety. PMID- 26150549 TI - Temporal trends in patient safety in the Netherlands: reductions in preventable adverse events or the end of adverse events as a useful metric? PMID- 26150551 TI - Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines. AB - An increasing body of evidence shows that the innate immune system has adaptive characteristics that involve a heterologous memory of past insults. Both experimental models and proof-of-principle clinical trials show that innate immune cells, such as monocytes, macrophages, and NK cells, can provide protection against certain infections in vaccination models independently of lymphocytes. This process is regulated through epigenetic reprogramming of innate immune cells and has been termed "trained immunity." It has been hypothesized that induction of trained immunity is responsible for the protective, nonspecific effects induced by vaccines, such as BCG, measles vaccination, and other whole microorganism vaccines. In this review, we will present the mechanisms of trained immunity responsible for the long-lasting effects of vaccines on the innate immune system. PMID- 26150550 TI - The Global Comparators project: international comparison of 30-day in-hospital mortality by day of the week. AB - OBJECTIVE: To examine the association of mortality by day of the week for emergency and elective patients. DESIGN: Retrospective observational study using the international dataset from the Global Comparators (GC) project consisting of hospital administrative data. SETTING: 28 hospitals from England, Australia, USA and the Netherlands during 2009-2012. PARTICIPANTS: Emergency and surgical elective patients. MAIN OUTCOME MEASURES: In-hospital deaths within 30 days of emergency admission or of elective surgery. RESULTS: We examined 2 982 570 hospital records; adjusted odds of 30-day death were higher for weekend emergency admissions to 11 hospitals in England (OR 1.08, 95% CI 1.04 to 1.13 on Sunday), 5 hospitals in USA (OR 1.13, 95% CI 1.04 to 1.24 on Sunday) and 6 hospitals in the Netherlands (OR 1.20, 95% CI 1.09 to 1.33 on Saturday). Emergency admissions to the six Australian hospitals showed no daily variation in adjusted 30-day mortality, but showed a weekend effect at 7 days post emergency admission (OR 1.12, 95% CI 1.04 to 1.22 on Saturday). All weekend elective patients showed higher adjusted odds of 30-day postoperative death; we observed a 'Friday effect' for elective patients in the six Dutch hospitals. CONCLUSIONS: We show that mortality outcomes for our sample vary within each country and per day of the week in agreement with previous studies of the 'weekend effect'. Due to limitations of administrative datasets, we cannot determine the reasons for these findings; however, the international nature of our database suggests that this is a systematic phenomenon affecting healthcare providers across borders. Further investigation is needed to understand the factors that give rise to the weekend effect. The participating hospitals represent varied models of service delivery, and there is a potential to learn from best practice in different healthcare systems. PMID- 26150552 TI - Physiological roles of connexins in labour and lactation. AB - The connexin family of proteins are best known as oligomerizing to form intercellular membrane channels (gap junctions) that metabolically and ionically couple cells to allow for coordinated cellular function. Nowhere in the body is this role better illustrated than in the uterine smooth muscle during parturition, where gap junctions conduct the contraction wave throughout the tissue to deliver the baby. Parturition is followed by the onset of lactation with connexins contributing to both the dramatic reorganization of mammary gland tissue leading up to lactation and the smooth muscle contraction of the myoepithelial cells which extrudes the milk. This review summarizes what is known about the expression and roles of individual connexin family members in the uterus during labour and in the mammary glands during development and lactation. Connexin loss or malfunction in mammary glands and the uterus can have serious implications for the health of both the mother and the newborn baby. PMID- 26150553 TI - Gene expression changes in subcutaneous adipose tissue due to Cushing's disease. AB - Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on the subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with nonfunctioning pituitary adenomas (n=11). We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids. PMID- 26150555 TI - Extracting transmission networks from phylogeographic data for epidemic and endemic diseases: Ebola virus in Sierra Leone, 2009 H1N1 pandemic influenza and polio in Nigeria. PMID- 26150558 TI - White House forum spotlights collaboration on antimicrobial stewardship. PMID- 26150554 TI - Cytoplasmic LSM-1 protein regulates stress responses through the insulin/IGF-1 signaling pathway in Caenorhabditis elegans. AB - Genes coding for members of the Sm-like (LSm) protein family are conserved through evolution from prokaryotes to humans. These proteins have been described as forming homo- or heterocomplexes implicated in a broad range of RNA-related functions. To date, the nuclear LSm2-8 and the cytoplasmic LSm1-7 heteroheptamers are the best characterized complexes in eukaryotes. Through a comprehensive functional study of the LSm family members, we found that lsm-1 and lsm-3 are not essential for C. elegans viability, but their perturbation, by RNAi or mutations, produces defects in development, reproduction, and motility. We further investigated the function of lsm-1, which encodes the distinctive protein of the cytoplasmic complex. RNA-seq analysis of lsm-1 mutants suggests that they have impaired Insulin/IGF-1 signaling (IIS), which is conserved in metazoans and involved in the response to various types of stress through the action of the FOXO transcription factor DAF-16. Further analysis using a DAF-16::GFP reporter indicated that heat stress-induced translocation of DAF-16 to the nuclei is dependent on lsm-1. Consistent with this, we observed that lsm-1 mutants display heightened sensitivity to thermal stress and starvation, while overexpression of lsm-1 has the opposite effect. We also observed that under stress, cytoplasmic LSm proteins aggregate into granules in an LSM-1-dependent manner. Moreover, we found that lsm-1 and lsm-3 are required for other processes regulated by the IIS pathway, such as aging and pathogen resistance. PMID- 26150556 TI - Association of hypertension and hyperglycaemia with socioeconomic contexts in resource-poor settings: the Bangladesh Demographic and Health Survey. AB - BACKGROUND: Cardiovascular diseases and risk factors are disproportionally concentrated among the socioeconomically disadvantaged in high-income countries; however, this relationship is not well-understood or documented in resource limited countries. METHODS: We analysed data from the 2011 Bangladesh Demographic and Health Survey to estimate age-, sex- and location-adjusted differences in blood pressure and blood glucose outcomes by categories of a standardized wealth index and education levels. Body mass index (BMI) was examined as a secondary outcome and also assessed as a potential confounder. RESULTS: There was strong evidence that the prevalence of hypertension was higher among Bangladeshi women than among men (33.6% vs 19.6%, P < 0.001), whereas the overall prevalence of hyperglycaemia was 7.1% with no evidence of sex differences. The likelihood of having hypertension was more than double for individuals in the highest vs lowest wealth quintile [odds ratio (OR) for men: 2.82, 95% confidence interval (CI): 2.32-3.44; OR for women: 2.25, 95% CI: 1.90-2.67], and for individuals with the highest level of education attained vs those with no education (OR for men: 2.55, 95% CI: 2.06-3.16; OR for women: 1.42, 95% CI: 0.99-2.03). Likewise, the likelihood of having hyperglycaemia was more than four times higher in the wealthiest compared with the poorest individuals (OR for men: 6.48, 95% CI: 5.11 8.22; OR for women: 4.77, 95% CI: 3.72-6.12), and in individuals with the highest level of education attained vs those with no education (OR for men: 4.68, 95% CI: 3.56-6.15; OR for women: 5.02, 95% CI: 3.30-7.64). There were no appreciable differences in these trends when stratified by geographical location. BMI did not attenuate these associations and exhibited similarly positive associations with education and wealth. CONCLUSIONS: Increasing levels of wealth and educational attainment were associated with an increased likelihood of having hypertension and hyperglycaemia in Bangladesh. PMID- 26150557 TI - Cohort Profile: The International Nuclear Workers Study (INWORKS). PMID- 26150559 TI - Pharmacists mull high-dose flu vaccine for seniors. PMID- 26150560 TI - Pharmacists respond to inflight medical event, perhaps prevent flight diversion. PMID- 26150561 TI - Drug information boot camp for pharmacy residents. PMID- 26150562 TI - Development of an administrative pharmacy residency in ambulatory care. PMID- 26150563 TI - Impact of the presidential executive order on decreasing antimicrobial resistance. PMID- 26150564 TI - Group medical visits as a tool for interprofessional team practice and implementation of the Pharmacy Practice Model Initiative. PMID- 26150565 TI - Skills and competencies for the new sterile-products manager. PMID- 26150566 TI - Maximizing your potential to promote the Pharmacy Practice Model Initiative as a student. PMID- 26150567 TI - A second-generation inhaled insulin for diabetes mellitus. AB - PURPOSE: The pharmacologic properties of a recently approved inhaled insulin product, its unique delivery system, and the results of clinical safety and efficacy trials are reviewed. SUMMARY: Afrezza (also called Technosphere Insulin, MannKind Corporation, Valencia, CA) is a novel ultrarapid-acting insulin formulation indicated for use in improving glycemic control in selected patients with type 1 or type 2 diabetes mellitus. Afrezza is not intended as a substitute for traditional basal therapy with injectable long-acting insulin but may be used to provide prandial insulin coverage; it must be used in combination with long acting insulin in patients with type 1 diabetes. Administered before meals using a dry-powder inhalation device, Afrezza is formulated with a novel excipient (fumaryl diketopiperazine) that dissolves instantly in lung fluid and releases recombinant human insulin for absorption. In clinical trials, rates of hypoglycemia in Afrezza-treated patients were significantly lower than rates reported in comparator groups receiving injectable insulin products. The most commonly reported adverse effect of Afrezza is coughing, which tends to occur shortly after inhalation and is typically mild. Afrezza is not recommended for use in patients who smoke (or have recently stopped smoking) and those with a chronic lung disease such as asthma or chronic obstructive pulmonary disease. Afrezza is not recommended for the treatment of diabetic ketoacidosis. CONCLUSION: Afrezza is a safe and effective treatment for selected adults with type 1 or type 2 diabetes, potentially providing an alternative to injectable insulin for prandial blood glucose control. PMID- 26150568 TI - Relationship between time spent at extreme International Normalized Ratios and time in therapeutic range with bleeding and thrombosis in warfarin-treated patients. AB - PURPOSE: The relationship between the time spent at extreme International Normalized Ratios (INRs) and the time in the therapeutic range (TTR) with bleeding and thrombosis in warfarin-treated patients was examined. METHODS: Consecutive patients treated with warfarin for atrial fibrillation or for venous thrombosis who were managed by the anticoagulation management service or adult internal medicine clinic of a large, tertiary care, integrated health system between June 1, 2011, and October 9, 2012, were eligible for study inclusion. Data collected for the outcomes analysis included INRs and dates; current use of aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, or nonsteroidal antiinflammatory drugs; and any clinically significant bleeding or thrombosis events identified. RESULTS: In the 837 patients who met the inclusion criteria, 636.5 patient-years of therapy were provided, of which 14.4 patient-years (2.26% of time) were spent at INRs of <1.5; 2.9 patient-years of therapy (0.45% of time) were spent at INRs of >4.5. The patient population had a mean individual TTR of 65%. The percentage of time at an INR of >4.5 was positively associated with an increased risk of major bleeding (p = 0.0085). The percentage of time spent with an INR of <1.5 was not associated with a significant increase in the risk of thrombosis. CONCLUSION: The percentage of time spent with an INR of >4.5 was associated with an increased risk of major bleeding in patients receiving warfarin for atrial fibrillation or for venous thrombosis at two outpatient clinics. The relationships between thrombosis risk and the TTR or the time spent at an INR of <1.5 were not significant, but the thromboembolic event rate was unusually low, as was the time spent at an INR of <1.5. PMID- 26150569 TI - Failure mode and effects analysis to reduce risk of anticoagulation levels above the target range during concurrent antimicrobial therapy. AB - PURPOSE: A failure mode and effects analysis (FMEA) was conducted to analyze the clinical and operational processes leading to above-target International Normalized Ratios (INRs) in warfarin-treated patients receiving concurrent antimicrobial therapy. METHODS: The INRs of patients on long-term warfarin therapy who received a course of trimethoprim-sulfamethoxazole, metronidazole, fluconazole, miconazole, or voriconazole (highly potentiating antimicrobials, or HPAs) between September 1 and December 31, 2011, were compared with patients on long-term warfarin therapy who did not receive any antimicrobial during the same period. A multidisciplinary team of physicians, pharmacists, and a systems analyst was then formed to complete a step-by-step outline of the processes involved in warfarin management and concomitant HPA therapy, followed by an FMEA. RESULTS: Patients taking trimethoprim-sulfamethoxazole, metronidazole, or fluconazole demonstrated a significantly increased risk of having an INR of >4.5. The FMEA identified 134 failure modes. The most common failure modes were as follows: (1) electronic medical records did not identify all patients receiving warfarin, (2) HPA prescribers were unaware of recommended warfarin therapy when HPAs were prescribed, (3) HPA prescribers were unaware that a patient was taking warfarin and that the drug interaction is significant, and (4) warfarin managers were unaware that an HPA had been prescribed for a patient. CONCLUSION: An FMEA determined that the risk of adverse events caused by concomitantly administering warfarin and HPAs can be decreased by preemptively identifying patients receiving warfarin, having a care process in place, alerting providers about the patient's risk status, and notifying providers at the anticoagulation clinic. PMID- 26150570 TI - Dispensing inhalers to patients with chronic obstructive pulmonary disease on hospital discharge: Effects on prescription filling and readmission. AB - PURPOSE: The effects of dispensing inhalers to patients with chronic obstructive pulmonary disease (COPD) on hospital discharge were evaluated. METHODS: Data were collected in 2011-12 for patients with COPD who had hospital orders for the study inhalers (preintervention group) and after implementation of the multidose medication dispensing on discharge (MMDD) service (2013-14) (postintervention group). The primary objective of this study was to assess inhaler adherence and readmission rates before and after MMDD implementation. Adherence was defined as filling the discharge prescription for the multidose inhaler at a Harris Health pharmacy within three days of discharge or having at least seven days of medication left in an inhaler from a previous prescription that was filled or refilled before hospital admission. All patients in the postintervention group were considered adherent, since every patient was given the remainder of his or her multidose inhaler when discharged. RESULTS: Data from 620 patients (412 in the preintervention group, 208 in the postintervention group) were collected. During the preintervention time period, 88 of 412 patients were readmitted within 30 days compared with 18 of 208 patients during the postintervention period (p < 0.001). The intervention was associated with a significant reduction in 30-day readmissions (p = 0.0016) and 60-day readmissions (p = 0.0056). CONCLUSION: A targeted pharmacy program to provide COPD patients being discharged from the hospital with the multidose inhalers they had used during hospitalization was associated with improved medication adherence, as measured by prescription filling behavior, and reduced rates of 30- and 60-day hospital readmissions. PMID- 26150571 TI - Pancreatic enzymes prepared in bicarbonate solution for administration through enteral feeding tubes. AB - PURPOSE: The dissolution and physicochemical effects of preparing delayed-release pancrelipase in a sodium bicarbonate solution before administration via an enteral feeding tube were studied. METHODS: Several doses of four delayed-release pancrelipase products (Creon, Pancreaze, Ultresa, Zenpep) were studied. The intact contents of pancrelipase capsules was added to 20 mL of 8.4% sodium bicarbonate solution to dissolve the enteric coating and liberate the enzymes into solution. In addition to visual observation, the pH, relative particle count, and osmolality of each admixture were assessed immediately and 5, 10, 20, and 30 minutes after admixture preparation. RESULTS: The only dose of Creon that was completely dissolved at 30 minutes was the 24,000 lipase unit dose. None of the doses of Pancreaze and only the lowest dose (23,000 lipase units) of Ultresa were completely dissolved at 30 minutes. However, Zenpep doses of 20,000 and 40,000 lipase units were completely dissolved 30 minutes after preparation. Higher doses of each pancrelipase product did not completely dissolve. The baseline pH of the solvent decreased slightly at the first few time points after pancrelipase was added. The relative particle count increased over time and with increasing doses. The osmolality of the mixtures varied by pancrelipase product. CONCLUSION: The dissolution of enteric coated granules in sodium bicarbonate varied with the pancrelipase product and dose. Zenpep 40,000 lipase units was found to most efficiently dissolve in sodium bicarbonate, possibly due to the consistent size of the product's granules and visibly thinner and uniform enteric coating. PMID- 26150572 TI - Evaluation of pharmacy resident alertness in an overnight on-call program. AB - PURPOSE: Results of a study to determine the impact of overnight on-call duty on pharmacy residents' alertness are presented. METHODS: A prospective single-site observational study was conducted to evaluate sleep patterns and alertness levels among pharmacy residents serving 24-hour on-call duty assignments at a large hospital. The study participants (n = 10) wore a wrist actigraph to allow continuous tracking of rest-activity patterns; in addition, study participants completed a validated three-minute psychomotor vigilance test (PVT) during designated time periods around the beginning and the end of each duty shift and several hours after the shift ended. Study participants also documented sleep quality and quantity in a sleep log and self-rated their level of alertness using the Karolinska sleepiness scale (KSS). RESULTS: Assessments were conducted for a total of 31 on-call duty shifts over one month. Paired comparisons of PVT data obtained at the three assessment periods indicated that on-call duty was not associated with significant changes in PVT performance measures (mean response speed and number of attention lapses). On average, on-call residents rated the quality of sleep during duty assignments as 5 on a 10-point Likert scale. CONCLUSION: On-call residents slept for a mean of six hours during overnight duty shifts, with half of the residents reporting sleep interruptions (a mean of 1.73 per shift). PVT results and KSS values indicated no overall decline in resident alertness during the study period. PMID- 26150573 TI - ASHP guidelines: Minimum standard for ambulatory care pharmacy practice. PMID- 26150574 TI - Heat training increases exercise capacity in hot but not in temperate conditions: a mechanistic counter-balanced cross-over study. AB - The aim was to determine the mechanisms facilitating exercise performance in hot conditions following heat training. In a counter-balanced order, seven males (Vo2max 61.2 +/- 4.4 ml.min(-1).kg(-1)) were assigned to either 10 days of 90-min exercise training in 18 or 38 degrees C ambient temperature (30% relative humidity) applying a cross-over design. Participants were tested for Vo2max and 30-min time trial performance in 18 (T18) and 38 degrees C (T38) before and after training. Blood volume parameters, sweat output, cardiac output (Q), cerebral perfusion (i.e., middle cerebral artery velocity [MCAvmean]), and other variables were determined. Before one set of exercise tests in T38, blood volume was acutely expanded by 538 +/- 16 ml with an albumin solution (T38A) to determine the role of acclimatization induced hypervolemia on exercise performance. We furthermore hypothesized that heat training would restore MCAvmean and thereby limit centrally mediated fatigue. Vo2max and time trial performance were equally reduced in T38 and T38A (7.2 +/- 1.6 and 9.3 +/- 2.5% for Vo2max; 12.8 +/- 2.8 and 12.9 +/- 2.8% for time trial). Following heat training both were increased in T38 (9.6 +/- 2.1 and 10.4 +/- 3.1%, respectively), whereas both Vo2max and time trial performance remained unchanged in T18. As expected, heat training augmented plasma volume (6 +/- 2%) and mean sweat output (26 +/- 6%), whereas sweat [Na(+)] became reduced by 19 +/- 7%. In T38 Qmax remained unchanged before (21.3 +/- 0.6 l/min) to after (21.7 +/- 0.5 l/min) training, whereas MCAvmean was increased by 13 +/- 10%. However, none of the observed adaptations correlated with the concomitant observed changes in exercise performance. PMID- 26150575 TI - Express Scripts? Really? PMID- 26150576 TI - Synergistic Interactions of Molecular and Clinical Advances for Characterizing the Myelodysplastic Syndromes. PMID- 26150577 TI - NCCN Evolving Through the Decades: A Continuum of Commitment and Mission. PMID- 26150578 TI - Clinical Sequencing Contributes to a BRCA-Associated Cancer Rediagnosis That Guides an Effective Therapeutic Course. AB - Cancer is currently classified and treated using an approach based on tissue of origin. Ambiguous or incorrect diagnoses, however, are common and often go unnoticed. Clinical cancer sequencing can provide diagnostic precision, therapeutic direction, and hereditary cancer risk assessment. This report presents a patient with an initial diagnosis of metastatic pancreatic adenocarcinoma (PDA), a disease with a dismal prognosis. Tumor sequencing revealed genomic abnormalities inconsistent with PDA, instead suggesting serous ovarian cancer. This molecular rediagnosis was further refined by the identification of a BRCA2 truncating mutation in the tumor, subsequently confirmed to be a germline event. These findings prompted the initiation of platinum-based chemotherapy, which produced a life-altering response, and referral to genetic counseling for her offspring. These results suggest that clinical tumor sequencing can simultaneously clarify diagnoses, guide therapy, and inform familial risk, even in patients with end-stage metastatic disease, making the case for the development of specific strategies to deploy sequencing coupled with big data in oncology to improve clinical cancer management. PMID- 26150580 TI - A Prospective Six Sigma Quality Improvement Trial to Optimize Universal Screening for Genetic Syndrome Among Patients With Young-Onset Colorectal Cancer. AB - BACKGROUND: Improving the quality of health care is a national priority, and providing patient-centered care is one of the 6 key areas for quality improvement. In the setting of patients with young-onset colorectal cancer (CRC), appropriate genetic workup and testing for potential underlying inherited CRC syndromes is fundamental to patient-centered care. Lynch syndrome (LS) is the most common of these inherited syndromes, and current recommendations from the NCCN and other professional societies advocate universal screening for LS among young patients with CRC. However, practical implementation of these guidelines often falls short. METHODS: We conducted a prospective quality improvement intervention trial to optimize universal screening for LS in young (age <50 years) patients, involving 356 eligible patients during the 12-month preintervention period and 299 patients during the postintervention. RESULTS: Applying the Six Sigma conceptual framework, we demonstrated a significant increase in use of tumor-based molecular testing and subsequent confirmatory germline mutation testing for LS. This led to identification of more patients to be managed as having LS and of more first- and second-degree relatives to benefit from the testing results. CONCLUSIONS: This study demonstrated the successful application of a quality improvement conceptual framework for the universal adoption of molecular biomarker testing in patients with cancer, and for improving adherence to NCCN Clinical Practice Guidelines in Oncology for CRC Screening. As molecular and genetic testing is becoming increasingly common, we present a prototype study for improving the adoption of molecular studies and the provision of guideline-based patient-centered care. PMID- 26150579 TI - Head and Neck Cancers, Version 1.2015. AB - These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages. PMID- 26150581 TI - A Prospective Analysis of Plasma Adiponectin and Risk of Incident Cancer: The Dallas Heart Study. AB - BACKGROUND: Adiponectin dysregulation is postulated to affect cancer risk via modulation of insulin resistance and inflammation. Epidemiologic studies evaluating this relationship have conflicting results and data from non-white cohorts are lacking. We examined the association between adiponectin and risk of cancer incidence in the multiethnic Dallas Heart Study (DHS). METHODS: Participants enrolled in the DHS and known adiponectin values were included. Incident cancer cases were identified through a systematic linkage of the DHS and the Texas Cancer Registry. Univariate/multivariate analysis were performed to test the association between adiponectin and incident cancer after adjusting for age, diabetes status, gender, ethnicity, C-reactive protein level, smoking status, and body mass index. Adiponectin level was evaluated both as a continuous variable and in race/ethnicity specific quartiles. RESULTS: Of 3444 individuals, there were 152 incident cancers. The study population was comprised of 44.4% men, and 51.05% were black. Baseline median adiponectin levels were 6.43 mcg/mL (interquartile range [IQR], 4.37-9.45 mcg/mL) in the incident cancer group versus 6.33 mcg/mL (IQR, 4.57-9.97 mcg/mL) in those without cancer. In multivariable analysis, adiponectin level was not associated with cancer incidence after adjusting for covariates. In analyses stratified by race/ethnic group, no association was observed in white, Hispanic, or African American subgroups. CONCLUSIONS: In this study of a predominant ethnic minority population, no association between adiponectin and cancer incidence was demonstrated. Despite preclinical rationale and confirmatory findings in other studies, this association may not replicate across all ethnic populations. Additional studies with strong minority representation are warranted to further examine this association. PMID- 26150582 TI - Breast Cancer Risk Reduction, Version 2.2015. AB - Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction. PMID- 26150583 TI - Menopausal Hormone Therapy Influence on Breast Cancer Outcomes in the Women's Health Initiative. AB - The Woman's Health Initiative has conducted 2 full-scale, placebo-controlled clinical trials to determine the influence of menopausal therapy on breast cancer incidence and outcome. Estrogen plus progestin use in postmenopausal women with a uterus increases breast cancer incidence and deaths from breast cancer. Despite a short-term reduction in risk after stopping estrogen plus progestin use, an increase in breast cancer risk persists postintervention. Estrogen-alone use in postmenopausal women with prior hysterectomy reduces breast cancer incidence and reduces deaths from breast cancer. The reduced breast cancer risk persists for several years after stopping estrogen-alone use but is lost in late postintervention. These findings suggest recalibration of breast cancer risk and benefit consideration for both regimens, with estrogen plus progestin use associated with greater risk and estrogen-alone use associated with greater benefit. Use of either regimen in clinical practice requires careful consideration of all clinical risks and benefits. PMID- 26150585 TI - Theorist's Toy: Equipoise. PMID- 26150584 TI - Barriers to the Use of Breast Cancer Risk Reduction Therapies. AB - Evidence from randomized clinical trials supports the use of tamoxifen, raloxifene, exemestane, and anastrozole for the reduction of risk of invasive breast cancer, predominately estrogen receptor-positive tumors. Revised clinical guidelines now strongly recommend that physicians offer high-risk women medication for breast cancer risk reduction. Although only a small portion of eligible women receive risk reduction medication, evidence suggests higher acceptance among women with atypical hyperplasia or lobular carcinoma in situ. Among physicians, barriers for prescribing risk reduction medications include inadequate training in risk assessment, lack of reimbursement for prevention counseling, and the unavailability of easily accessible and user-friendly prediction tools for estimating risk/benefit profiles. Strategies to improve uptake among women have focused on providing education about breast cancer risk and information that accurately conveys the risks and benefits of risk reduction medications. Priority areas of research that have been identified to improve the use of risk reduction medications are the (1) development of risk assessment tools that more accurately identify women most likely to benefit, (2) identification of circulating or tissue biomarkers that can predict and monitor responsiveness of treatment, and (3) better understanding of patient-related barriers, including patients' subjective beliefs and experiences. PMID- 26150586 TI - Strategies to Circumvent Testosterone Surge and Disease Flare in Advanced Prostate Cancer: Emerging Treatment Paradigms. AB - The testosterone surge and disease flare is a feared complication from initiation of gonadotropin-releasing hormone (GnRH) agonist treatment in advanced prostate adenocarcinoma. It is a common practice to start an average 7-day pretreatment regimen with an antiandrogen agent before initiating GnRH agonist therapy, to circumvent disease flare from testosterone surge. However, this might not be the best strategy and can be harmful, especially in patients at high risk of imminent organ damage from minimal testosterone surge. Surgical castration is a simple and cost-effective method that should be considered in these scenarios. But most patients refuse this procedure because of the permanent and psychologic impact of surgery. Novel GnRH antagonists, such as degarelix, and cytochrome P450 17 (CYP17) enzyme inhibitors, such as ketoconazole, achieve castrate-equivalent serum testosterone levels much faster than traditional GnRH agonists without the need for coadministration of antiandrogens. This article reports on 3 cases of impending oncologic emergencies in advanced prostate adenocarcinoma treated promptly with degarelix and ketoconazole without any disease flare related to testosterone surge. In the setting of symptomatic hormone-naive metastatic prostate cancer, the authors suggest clinical trials using abiraterone, orteronel, and other newer agents that target the CYP17 axis (eg, ketoconazole) for fine-tuning the emergent medical castration methods and avoiding the dangers from the flare phenomenon. PMID- 26150588 TI - Relative strain in the anterior cruciate ligament and medial collateral ligament during simulated jump landing and sidestep cutting tasks: implications for injury risk. AB - BACKGROUND: The medial collateral (MCL) and anterior cruciate ligaments (ACL) are, respectively, the primary and secondary ligamentous restraints against knee abduction, which is a component of the valgus collapse often associated with ACL rupture during athletic tasks. Despite this correlation in function, MCL ruptures occur concomitantly in only 20% to 40% of ACL injuries. HYPOTHESIS/PURPOSE: The purpose of this investigation was to determine how athletic tasks load the knee joint in a manner that could lead to ACL failure without concomitant MCL failure. It was hypothesized that (1) the ACL would provide greater overall contribution to intact knee forces than the MCL during simulated motion tasks and (2) the ACL would show greater relative peak strain compared with the MCL during simulated motion tasks. STUDY DESIGN: Controlled laboratory study. METHODS: A 6-degrees-of freedom robotic manipulator articulated 18 cadaveric knees through simulations of kinematics recorded from in vivo drop vertical jump and sidestep cutting tasks. Specimens were articulated in the intact-knee and isolated-ligament conditions. After simulation, each ACL and MCL was failed in uniaxial tension along its fiber orientations. RESULTS: During a drop vertical jump simulation, the ACL experienced greater peak strain than the MCL (6.1% vs 0.4%; P < .01). The isolated ACL expressed greater peak anterior force (4.8% vs 0.3% body weight; P < .01), medial force (1.6% vs 0.4% body weight; P < .01), flexion torque (8.4 vs 0.4 N.m; P < .01), abduction torque (2.6 vs 0.3 N.m; P < .01), and adduction torque (0.5 vs 0.0 N.m; P = .03) than the isolated MCL. During failure testing, ACL specimens preferentially loaded in the anteromedial bundle failed at 637 N, while MCL failure occurred at 776 N. CONCLUSION: During controlled physiologic athletic tasks, the ACL provides greater contributions to knee restraint than the MCL, which is generally unstrained and minimally loaded. CLINICAL RELEVANCE: Current findings support that multiplanar loading during athletic tasks preferentially loads the ACL over the MCL, leaving the ACL more susceptible to injury. An enhanced understanding of joint loading during in vivo tasks may provide insight that enhances the efficacy of injury prevention protocols. PMID- 26150589 TI - The optimum tension for bridging sutures in transosseous-equivalent rotator cuff repair: a cadaveric biomechanical study. AB - BACKGROUND: Transosseous-equivalent (TOE) rotator cuff repair can increase contact area and contact pressure between the repaired cuff tendon and bony footprint and can show higher ultimate loads to failure and smaller gap formation compared with other repair techniques. However, it has been suggested that medial rotator cuff failure after TOE repair may result from increased bridging suture tension. PURPOSE: To determine optimum bridging suture tension in TOE repair by evaluating footprint contact and construct failure characteristics at different tensions. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 18 fresh frozen cadaveric shoulders, randomly divided into 3 groups, were constructed with a TOE configuration using the same medial suture anchor and placing a Tekscan sensing pad between the repaired rotator cuff tendon and footprint. Nine of the 18 shoulders were used to measure footprint contact characteristics. With use of the Tekscan measurement system, the contact pressure and area between the rotator cuff tendon and greater tuberosity were quantified for bridging suture tensions of 60, 90, and 120 N with glenohumeral abduction angles of 0 degrees and 30 degrees and humeral rotation angles of 30 degrees (internal), 0 degrees , and 30 degrees (external). TOE constructs of all 18 shoulders then underwent construct failure testing (cyclic loading and load to failure) to determine the yield load, ultimate load, stiffness, hysteresis, strain, and failure mode at 60 and 120 N of tension. RESULTS: As bridging suture tension increased, contact force, contact pressure, and peak pressure increased significantly at all positions (P < .05 for all). Regarding contact area, no significant differences were found between 90 and 120 N at all positions, although there were significant differences between 60 and 90 N. The construct failure test demonstrated no significant differences in any parameters according to various tensions (P > .05 for all). CONCLUSION: Increasing bridging suture tension to over 90 N did not improve contact area but did increase contact force and pressure. Bridging suture tension did not significantly affect ultimate failure loads. CLINICAL RELEVANCE: Considering the risks of overtensioning bridging sutures, it may be clinically more beneficial to keep bridging suture tension below 90 N. PMID- 26150590 TI - M-Trap: Exosome-Based Capture of Tumor Cells as a New Technology in Peritoneal Metastasis. AB - BACKGROUND: Remodeling targeted tissues for reception of tumor cells metastasizing from primary lesions is a consequence of communication between the tumor and the environment that governs metastasis. This study describes a novel approach that aims to disrupt the process of metastasis by interfering with this intense dialogue. METHODS: Proteomics and adhesion assays identified exosomes purified from the ascitic fluid of ovarian cancer patients (n = 9) as intermediaries of tumor cell attachment. A novel tumor cell capture device was fabricated by embedding exosomes onto a 3D scaffold (metastatic trap [M-Trap]). Murine models of ovarian metastasis (n = 3 to 34 mice per group) were used to demonstrate the efficacy of M-Trap to capture metastatic cells disseminating in the peritoneal cavity. Kaplan-Meier survival curves were used to estimate cumulative survival probabilities. All statistical tests were two-sided. RESULTS: The exosome-based M-Trap device promoted tumor cell adhesion with a nonpharmacological mode of action. M-Trap served as a preferential site for metastasis formation and completely remodeled the pattern of peritoneal metastasis in clinically relevant models of ovarian cancer. Most importantly, M Trap demonstrated a statistically significant benefit in survival outcomes, with mean survival increasing from 117.5 to 198.8 days in the presence of M-Trap; removal of the device upon tumor cell capture further improved survival to a mean of 309.4 days (P < .001). CONCLUSIONS: A potent artificial premetastatic niche based on exosomes is an effective approach to impair the crosstalk between metastatic cells and their environment. In the clinical setting, the capacity to modulate the pattern of dissemination represents an opportunity to control the process of metastasis. In summary, M-Trap transforms a systemic, fatal disease into a focalized disease where proven therapeutic approaches such as surgery can extend survival. PMID- 26150591 TI - Style, spin, and science. PMID- 26150592 TI - Retinal and intracranial hemorrhage in acute leukemic disseminated intravascular coagulation. PMID- 26150593 TI - Pulse-synchronous pendular nystagmus following cholesteatoma surgery. PMID- 26150594 TI - Early symptom burden predicts recovery after sport-related concussion. PMID- 26150598 TI - Teaching NeuroImages: Isolated peripheral facial palsy due to ipsilateral pontine infarction. PMID- 26150599 TI - Teaching NeuroImages: Superior divisional oculomotor nerve palsy due to orbital lymphoma. PMID- 26150600 TI - Teaching NeuroImages: Fetal deep medullary vein thrombosis presenting as progressive intracerebral hemorrhage. PMID- 26150601 TI - A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. AB - OBJECTIVES: To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. METHODS: This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24 week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured. RESULTS: 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was -9.41% to 4.98%, which is completely contained within the predefined equivalence margin of -15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%). CONCLUSIONS: SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN. TRIAL REGISTRATION NUMBERS: NCT01895309, EudraCT 2012-005026-30. PMID- 26150605 TI - The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease. AB - The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score <=3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD. PMID- 26150606 TI - Regulation of Mg2+ Reabsorption and Transient Receptor Potential Melastatin Type 6 Activity by cAMP Signaling. AB - The transient receptor potential melastatin type 6 (TRPM6) epithelial Mg(2+) channels participate in transcellular Mg(2+) transport in the kidney and intestine. Previous reports suggested a hormonal cAMP-dependent regulation of Mg(2+) reabsorption in the kidney. The molecular details of this process are, however, unknown. Adenylate cyclase 3 (Adcy3) has been shown to colocalize with the Na(+)/Cl(-) cotransporter, a marker of the distal convoluted segment of the kidney, the principal site of TRPM6 expression. Given the critical role of TRPM6 in Mg(2+) reabsorption, an inducible kidney-specific Adcy3 deletion mouse model was characterized for blood and urinary electrolyte disturbances under a normal- and low--Mg(2+) diet. Increased urinary Mg(2+) wasting and Trpm6 mRNA levels were observed in the urine and kidney of Adcy3-deleted animals compared with wild-type controls. Serum Mg(2+) concentration was significantly lower in Adcy3-deleted animals at day 7 on the low Mg(2+) diet. Using patch clamp electrophysiology, cell surface biotinylation, and total internal reflection fluorescence live cell imaging of transfected HEK293 cells, we demonstrated that cAMP signaling rapidly potentiates TRPM6 activity by promoting TRPM6 accumulation at the plasma membrane and increasing its single-channel conductance. Comparison of electrophysiological data from cells expressing the phosphorylation-deficient S1252A or phosphomimetic S1252D TRPM6 mutants suggests that phosphorylation at this intracellular residue participates in the observed stimulation of channel activity. Altogether, these data support a physiologically relevant magnesiotropic role of cAMP signaling in the kidney by a direct stimulatory action of protein kinase A on the plasma membrane trafficking and function of TRPM6 ion channels. PMID- 26150608 TI - Double frenum weds fusion: a rare wedlock? AB - Morphological variation of normal oral structures such as double frenum and fusion together in a patient is rare. Sometimes such scenarios may mislead the diagnosis, affecting treatment planning and prognosis. Hence a thorough evaluation of patients with such morphological defects is necessary. This case report describes a case of double frenum and fusion, and the multiple challenges the clinician faces. PMID- 26150607 TI - Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects. AB - APOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOL1-associated kidney injury, we analyzed clinical and genomic datasets derived from 90 black subjects in the Nephrotic Syndrome Study Network (NEPTUNE), stratified by APOL1 risk genotype. Ninety subjects with proteinuria >=0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome and followed. Clinical outcomes were determined, and renal histomorphometry and sequencing of Mendelian nephrotic syndrome genes were performed. APOL1 variants were genotyped, and glomerular and tubulointerstitial transcriptomes from protocol renal biopsy cores were analyzed for differential and correlative gene expression. Analyses were performed under the recessive model (high-risk genotype defined by two risk alleles). APOL1 high-risk genotype was significantly associated with a 17 ml/min per 1.73 m(2) lower eGFR and a 69% reduction in the probability of complete remission at any time, independent of histologic diagnosis. Neither APOL1 risk group was enriched for Mendelian mutations. On renal biopsy, high-risk genotype was associated with increased fractional interstitial area, interstitial fibrosis, and tubular atrophy. Risk genotype was not associated with intrarenal APOL1 mRNA expression levels. Differential expression analysis demonstrated an increased steady-state level of five genes associated with the high-risk genotype (CXCL9, CXCL11, and UBD in glomerulus; SNOR14B and MUC13 in tubulointerstitium). APOL1 tubulointerstitial coexpression analysis showed coexpression of APOL1 mRNA levels with a group of intrarenal transcripts that together were associated with increased interstitial fibrosis and tubular atrophy. These data indicate the high-risk APOL1 genotype confers renal risk across histopathologic diagnoses. PMID- 26150609 TI - Optical coherence tomography imaging of the optic nerve head pre optic and post optic nerve sheath fenestration. AB - Idiopathic intracranial hypertension (IIH) is a disorder of unknown aetiology, and causes elevated intracranial pressures. This is often associated with papilloedema with subsequent degrees of optic atrophy if the intracranial pressures are not controlled in a timely manner. Optical coherence tomography imaging is widely recognised for its use in the monitoring of optic nerves in glaucoma, and this report is the first to describe its use to monitor the optic nerve head pre optic and post optic nerve sheath fenestration. PMID- 26150610 TI - Individualised dual antiplatelet therapy in a patient with short bowel syndrome after acute myocardial infarction with coronary artery stenting. AB - Short bowel syndrome after extensive surgical resection of the intestine is characterised by inadequate digestion and absorption of nutrients. Additional clinical problems include impaired absorption and metabolism of diverse drugs requiring individualised medical therapy or alternative treatments. We report a case of individualised dual antiplatelet therapy in a patient who underwent an extensive intestinal resection complicated by acute myocardial infarction requiring percutaneous coronary intervention and stent implantation. Genetic testing of CYP2C19 gene polymorphisms and platelet aggregation testing were used to assess responses to aspirin, clopidogrel, prasugrel and ticagrelor. Given its unique pharmacokinetics with good absorption and without need of metabolism to an active substance, ticagrelor appears to be the best for patients with short bowel syndrome who require dual antiplatelet therapy after coronary stent implantation. PMID- 26150611 TI - Gastritis as a manifestation of primary CMV infection in an immunocompetent host. AB - The cytomegalovirus (CMV) disease spectrum is very wide, with symptomatic infections being rare in immunocompetent hosts. We present the case of a 31-year old immunocompetent man diagnosed with CMV gastritis in the context of primary infection. The most important laboratory abnormalities leading to diagnosis were: elevation of liver enzymes (3-4* the upper limit of normal), thrombocytopenia (133 G/L), lymphocytosis (55%-4.2 G/L) with activated lymphocytes, CMV IgM positive (negative IgG), CMV viral load of 5700 copies/mL (real-time PCR); autoimmunity study showed antiparietal cell antibodies; abdominal ultrasonography detected homogenous splenomegaly (14.6*13.4 cm) and endoscopy unveiled superficial erosions of the gastric antrum that were biopsied. Anatomopathology and immunohistochemistry of the samples identified cytomegalic inclusions in endothelial cells. Cellular and humoral immunity deficits were excluded. As the patient developed severe asthaenia, adynamia and epigastric pain, he was administered gancyclovir 5 mg/kg intravenously twice daily for 7 days, with resolution of symptoms and gastric lesions confirmed by re-evaluation through endoscopy. PMID- 26150612 TI - Postpartum vertebral artery dissection with posterior reversible encephalopathy syndrome. AB - We diagnosed postpartum eclampsia with posterior reversible encephalopathy syndrome (PRES) in a 35-year-old woman who began experiencing headaches after delivery. Cervical MR angiography (MRA) suggested concomitant vertebral artery (VA) dissection. Antiplatelet therapy was not indicated. Each episode resolved spontaneously. The patient subsequently developed sudden onset of thunderclap headache. She experienced a tonicoclonic seizure in the outpatient clinic. On the basis of clinical course and MRI, we diagnosed postpartum eclampsia with PRES. Antiplatelet therapy was not indicated, as there were no signs of stroke. Antiepileptic and antihypertensive medicines were used for a short term to control seizure and blood pressure. Subsequent MRI 17 days after discharge showed resolution of the abnormal signals, but the intramural heme signals became apparent on the dissecting segment of VA. Subsequent MRI after 3 months indicated resolution of arterial dissection. To the best of our knowledge, this represents the third report of postpartum cervicocephalic artery dissection with PRES in the literature. PMID- 26150613 TI - Eosinophilic pneumonia presenting as life-threatening ARDS. AB - We present a case of a 25-year-old woman with sudden onset of shortness of breath, cough and malaise, 24 h after discharge from a psychiatric hospital. She had been there for 2 weeks after a suicide attempt with lye, and started treatment with paroxetin, alprazolam and valproic acid. She also started smoking 20 cigarettes/day during that hospital admission. Brought to the emergency department, she evolved in the first 24 h with respiratory failure and shock needing intensive care unit (ICU) admission, with mechanical ventilation and vasopressor support. Empiric antibiotic therapy was started (piperacillin tazobactam and azithromycin) suspecting healthcare-associated pneumonia. The patient's chest radiography progressed with bilateral infiltrates. Peripheral blood eosinophilia was seen on the second day. A bronchoalveolar lavage was performed and had 50% of eosinophils. She was started on treatment with steroids and the next day no longer needed vasopressors; 4 days later she was extubated. PMID- 26150614 TI - Juvenile allergic urethritis with urethro-ejaculatory reflux presenting as acute intermittent bilateral testicular torsion. AB - We report a case of juvenile allergic urethritis secondary to double concentrate orange squash of a famous brand in a 3-year-old boy who developed bilateral urethro-ejaculatory reflux (UER) and severe urethral, perineal and scrotal pain referred to both lower limbs intermittently predominantly during and after micturition-simulating features of bilateral intermittent testicular torsion. Accurate history, urinalysis, ultrasound, colour Doppler and food challenge were helpful in diagnosis. Topical steroids, antihistaminic, analgesic and anti inflammatory medications together with withdrawal of the allergen produced complete recovery. Allergic urethritis in association with bilateral UER causing secondary seminal vesiculitis and epididymitis is rare. It presented as acute scrotum and responded to innovative treatment. Allergic disease can have a dramatic effect on a child's quality of life. This is the first documented case of allergic urethritis and associated UER presenting as juvenile acute scrotum. Steroids, antihistamines and anti-inflammatory agents together with avoidance of the allergen helped achieve recovery. PMID- 26150615 TI - Wireless capsule endoscopy as a tool in diagnosing autoimmune enteropathy. AB - Autoimmune enteropathy (AE) is an immune mediated illness of the intestinal mucosa. The cause is unknown, and the diagnosis is based on typical characteristics displayed. There is no gold standard for treatment. We present two adult cases of AE and demonstrate the challenges in establishing the diagnosis. The extensive diagnostic work up excluded other more common causes of protracted diarrhoea. Wireless capsule endoscopy (WCE) displayed universal small intestinal mucosal damage with shortened villi that led to the suspicion of AE in both patients. The diagnosis was confirmed with microscopy, showing shortened villi, villous blunting and hyperplasia of crypts in both patients. In one patient, deep crypt lymphocytosis with minimal intraepithelial lymphocytosis was found as well. Both patients were successfully treated with high-dose immunosuppressant therapy to induce and maintain remission. Use of WCE as a diagnostic tool was invaluable in establishing the diagnosis of AE. PMID- 26150616 TI - A case of neurosarcoidosis secondary to treatment of etanercept and review of the literature. AB - There are only three cases in the literature that describe development of neurosarcoidosis in a patient who is on tumour necrosis factor alpha inhibitors. We describe a case of a 33-year-old woman with a history of juvenile rheumatoid arthritis and refractory uveitis (with previous treatment trials of adalimumab, infliximab, mycophenolate, methotrexate) who had been stable for 2 years on etanercept. She was diagnosed with biopsy-proven systemic sarcoidosis with meningeal and parenchymal neurosarcoidosis. She was switched to infliximab and methotrexate, with clinical and imaging improvements. This is a case that demonstrates the difficulty of choosing tumour necrosis factor alpha (TNF-alpha) inhibitors when treating patients with multiple clinical autoimmune entities. It is also a case where a change in the mechanism of TNF-alpha inhibition pathway can still be used to treat refractory sarcoidoisis and rheumatoid arthritis. It is still unclear what the exact difference between the TNF-alpha blockers and their neurological complications is, and who the patients at risk of developing neurological complications are. PMID- 26150617 TI - A 79-year-old-man with a 'niveau' on a chest radiograph. AB - A 79-year-old man was referred to the emergency room following a sudden episode of 'spitting blood', with a blood pressure of 128 (systolic) and 75 mm Hg (diastolic) and a heart rate of 60 bpm. His medical history included the treatment of gastric cancer and untreated hypertension. At that time, his symptoms were limited without any chest, back or abdominal pain. After a presentation of haemoptysis was confirmed, a chest radiograph revealed an air fluid level (a 'niveau') that was continuous towards the enlarged thoracic aorta and the thoracic cavity. Contrast-enhanced CT was subsequently performed, and revealed an aortic dissection and a pneumothorax adjacent to the dissection, accompanied by blood pooling in the thoracic cavity. The patient died 40 min after the admission to the emergency room due to an additional haemoptysis. The autopsy confirmed the diagnosis of a ruptured aortic dissection with pneumothorax. PMID- 26150618 TI - Co-occurrence of rheumatoid arthritis and sarcoidosis. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by erosive arthritis. Sarcoidosis is a chronic disease characterised by formation of non-calcified granulomas. Our case, a 35-year-old woman, presented with metacarpophalangeal, proximal interphalangeal (PIP) joints and arthritis of both ankles, of 6-month duration. She had morning stiffness lasting 1 h, restriction of range of motion and erythaema nodosum. Laboratory tests showed elevated acute phase responses and serum ACE levels, and anti-cyclic citrullinated peptide antibody positivity. There was periarticular osteoporosis on her hand and wrist on direct X-rays and hilar lymphadenopathy on her thorax CT. The pathological result of endobronchial ultrasound biopsy showed non-calcified granuloma congruent with sarcoidosis. According to clinical, laboratory and histopathological evaluation, the patient was diagnosed with RA and sarcoidosis. Corticosteroids and methotrexate were started, and on her sixth month of follow up, her clinical and laboratory findings and lymphadenopathies on CT had regressed. The clinical follow-up continues; the patient appears to be in clinical remission. PMID- 26150619 TI - BRCA 1/2 gene mutation and gastrointestinal stromal tumours: a potential association. AB - Mutations of the BRCA1/2 genes have been described in association with a number of malignancies including cancers of the breast, ovary, prostate and stomach, but have never been described in relation to gastrointestinal stromal tumours (GIST). We describe a patient with a BRCA2 8642del3insC mutation who developed prostate cancer, breast cancer and GIST. GIST has been shown to be associated with a number of malignancies, including some of the common BRCA1/2-related cancers, but it has never been associated with BRCA1/2 gene mutations. This report highlights the potential association between BRCA1/2 mutations and GIST, and aims to raise awareness for further genetic screening in GIST patients. PMID- 26150620 TI - Femoral-facial syndrome in an infant of a diabetic mother. AB - Femoral-facial syndrome (FFS) is a very rare multiple congenital anomaly syndrome. The authors describe a case of FFS in a 2-day-old infant of a diabetic mother. The phenotypic features include bilateral symmetrical femoral involvement with completely aplastic right-sided femur, severely hypoplastic left femur and unusual facial dysmorphic features without other skeleton/spinal and genitourinary anomalies. Cases of FFS need to be carefully evaluated because of the similarity between FFS and caudal dysgenesis, a condition frequently related to maternal diabetes and with other syndromes characterised by femoral hypoplasia and associated anomalies, which can pose a diagnostic challenge. PMID- 26150621 TI - Transverse myelitis caused by hepatitis E: previously undescribed in adults. AB - We report the case of a 62-year-old Caucasian woman who was admitted with urinary retention and lower limb paraesthesia following a week's prodromal illness of headache and malaise. Liver function tests showed a picture of acute hepatocellular dysfunction. She developed reduced lower limb power, brisk reflexes, extensor plantars, a sensory level at T8 and reduced anal sphincter tone, establishing a clinical diagnosis of transverse myelitis. A spinal MRI showed no evidence of cauda equina or spinal cord compression. Cerebrospinal fluid (CSF) analysis showed raised protein and raised white cell count. Hepatitis E IgM and IgG were positive and hepatitis E virus was found in her CSF. She was treated with methylprednisolone and is slowly recovering with physiotherapy. PMID- 26150622 TI - Chyluria: a scourge of our region. AB - Chyluria is endemic in the Gangetic belt of India with an average of 90 cases treated annually at our institute. It is almost exclusively caused by Wuchereria bancrofti in tropical areas. Chylomicrons and triglycerides are lost in the urine from an abnormal lymphourinary fistula due to obstructive lymphatic stasis, most commonly at the renal pelvis. It is a distressingly recurrent condition with multiple exacerbations and remissions over years. Severe weakness, weight loss and haematuria occur in some patients. Diagnosis can be made by visual examination of milky urine along with the ether test of urine for chylomicrons. Intravenous urography is used to locate the site of the fistula, although the detection rate is poor. Treatment starts with conservative measures such as a high-protein low-fat diet and diethylcarbamazine therapy. In cases where conservative measures fail, endoscopic sclerotherapy (renal pelvic instillation of silver nitrate, povidone iodine or others) and surgical therapy are used. PMID- 26150623 TI - A novel surgical approach for treatment of sigmoid gallstone ileus. AB - We report a rare case of large bowel obstruction secondary to a gallstone impacted within the sigmoid colon, in the presence of sigmoid diverticular disease. An 89-year-old woman presented with an 8-day history of increasing abdominal distension, pain and associated nausea. Abdominal X-ray demonstrated large bowel dilation. CT scan revealed a fistula between an inflamed gallbladder and the hepatic flexure of the colon, with a large gallstone in the sigmoid colon. Proximal dilated large bowel was evident to the caecum. Flexible sigmoidoscopy was performed as the least invasive potential treatment method with a view to basket retrieval or fragmentation of the stone. Owing to poor views and risk of diverticular perforation, the procedure was abandoned, hence laparotomy was performed. Antegrade manipulation and per-rectal evacuation were attempted but failed due to a thickened, angulated sigmoid colon. Retrograde milking of the stone to the caecum and retrieval via modified appendicectomy was successful. PMID- 26150624 TI - Molten metal ocular burn: long-term outcome using simple limbal epithelial transplantation. AB - One day after molten aluminium had fallen into his right eye, a young man presented to our clinic with a vision of counting fingers at 1 m, conjunctival and corneal epithelial defects, and limbal involvement. He was diagnosed with grade 4 thermal burn and managed medically. Subsequently, the inflammation resolved, however, he developed pannus with conjunctivalisation and scarring of cornea suggestive of partial unilateral limbal stem cell deficiency. He was treated surgically with autologous simple limbal epithelial transplantation (SLET). Postoperatively, his vision improved along with corneal clarity. He achieved a best corrected vision of 20/50 at the last follow-up 27 months postsurgery, with maintenance of a healthy corneal epithelium. This case describes the different management strategies employed in two different stages of an ocular burn. It highlights the long-term success of SLET in a case of ocular surface thermal burn. PMID- 26150625 TI - Vertebral-venous fistula: an unusual cause for ocular symptoms mimicking a carotid cavernous fistula. AB - Vertebral-venous fistulas (VVF), or vertebral-vertebral arteriovenous fistulas, are an uncommon clinical entity. Typically, they present as a result of a direct vascular connection between an extracranial branch of the vertebral artery or its radicular components and the epidural venous plexus. These may manifest with signs and symptoms referable to cervical myelopathy secondary to compression or steal phenomenon. To our knowledge, this is the first case to identify a patient who presented with classic ocular symptoms attributable to a carotid cavernous fistula but secondary to a VVF. We present its treatment and clinical outcome. In addition, we present a brief literature review surrounding this uncommon disease. PMID- 26150626 TI - Acute ischemic stroke in a child due to basilar artery occlusion treated successfully with a stent retriever. AB - Ischemic strokes in childhood are rare. Thrombolytic therapy with intravenous (IV) tissue plasminogen activator (tPA) has been the main intervention for the management of pediatric stroke patients, but safety data are lacking and efficacy has been questioned. Recently, successful endovascular treatments for acute ischemic stroke in children have been reported with increasing frequency, suggesting that mechanical thrombectomy can be a safe and effective treatment. We present the case of a 22-month-old child with acute ischemic stroke due to basilar artery occlusion that was successfully treated with a stent retriever. PMID- 26150627 TI - Spontaneous thrombosis of a basilar tip aneurysm after ventriculoperitoneal shunting. AB - We present a case of a large unruptured basilar tip aneurysm with concomitant hydrocephalus. Complete thrombosis of the aneurysm was observed after ventriculoperitoneal shunting. Analyzing preoperative and postoperative MRI and DSA images, we identified reduced intracranial pressure and widening of the aneurysm-artery inclination angle as possible factors influencing spontaneous thrombosis. To the best of our knowledge, this is the first report of aneurysm thrombosis occurring after CSF diversion. PMID- 26150628 TI - Acute necrotising pancreatitis derived from low-dose corticosteroid use: an important reminder of clinical management. AB - Although the exact mechanism is unknown, incidence of drug-induced pancreatitis from corticosteroids is well established in the medical literature. Commonly reported in chronic steroid-dependent individuals who require large doses for a wide array of pathologies, the incidence of damage to the pancreas from low-doses have not been well described. We report a case of a 68-year-old woman who presented with severe abdominal pain, nausea and vomiting, 3 days after the initiation of low-dose methylprednisolone for osteoarthritis. Inpatient laboratory analysis revealed an elevated lipase of 1770 U/L and CT scan showing extensive necrotising pancreatitis involving the head, body and tail. Cessation of the causative medication and conservative treatment successfully led to resolution of symptoms. We present this case to inform clinicians of the precipitance of pancreatitis from modest strength corticosteroid management, so that more accurate and improved performance in pharmacological decisions can be made for patient care. PMID- 26150629 TI - Oesophageal lesions as first manifestation of necrotising sarcoid granulomatosis. AB - Necrotising sarcoid granulomatosis is a rare disease associating sarcoid-like granulomas, vasculitis and necrosis in the lungs and seldom in extrapulmonary locations. We report the case of a 23-year-old woman with an initial symptom consisting of epigastric pain. Oesophagoscopy demonstrated oesophagitis. Evolution was marked by fever, dyspnoea and pulmonary lesions. The first presumptive diagnosis was Wegener disease but biopsies (of the lungs and the oesophagus) demonstrated the diagnosis of necrotising sarcoid granulomatosis. Evolution was favourable under corticoid therapy. Necrotising sarcoid granulomatosis may present as an extrapulmonary disease and is an important differential diagnosis of other disease such as Wegener disease. PMID- 26150630 TI - Novel surgical management of a laryngeal granular cell tumour. AB - Granular cell tumour (GCT) is a rare benign tumour occurring, most commonly, in the head and neck. Multiple tumours occur in 5-16% of patients. These tumours are chemo-radio-resistant and have high recurrence rates despite their benign histopathological features. Traditional management, depending on access, involves total tumour resection with wide margins due to the high rates of recurrence with incomplete resection. We present a patient with two synchronous GCTs of their upper airway: in the larynx and the trachea. Complete excision of the supraglottic lesion would have rendered the patient's larynx incompetent. Therefore, after multidisciplinary team (MDT) discussion, and following a discussion with the patient regarding the risks and benefits, a novel surgical management approach was agreed. Subtotal CO2 laser excision of the upper GCT was performed enabling functional organ preservation. A subsequent procedure was required when the patient became symptomatic due to tumour recurrence. PMID- 26150631 TI - A multidisciplinary approach to an unusual cause of hyperamylasaemia. AB - Clinical features together with elevation of pancreatic enzymes are the key diagnostic indicators of acute pancreatitis. We report a case of a woman in her 50s who presented with abdominal distension and serum amylase raised to more than 30 times the upper limit of normal. She was initially treated for acute pancreatitis, however, she was not symptomatic of this and the pancreas appeared to be normal on CT scan. Further investigations revealed the patient had a high grade serous ovarian carcinoma with nodal metastatic spread. An amylase-secreting ovarian tumour was suspected, which was supported by elevated salivary-amylase isoenzymes, consistent with previous reports in the literature. The patient was treated with chemotherapy and surgery, during which her serum amylase and CA-125 initially fell significantly, but eventually both increased, reflecting disease progression. This case serves as an important reminder to consider non-pancreatic causes of raised serum amylase, to avoid misdiagnosis. PMID- 26150632 TI - Dramatic change in a young woman's perception of her diabetes and remarkable reduction in HbA1c after an individual course of Guided Self-Determination. AB - A 24-year-old woman with type 1 diabetes participated in a randomised controlled trial proving effectiveness of a flexible Guided Self-Determination (GSD) intervention. She had for 10 years been living with a complex situation of eating disorder, poor glycaemic control, non-attendance and psychosocial distress. She managed to change her perception of diabetes dramatically and improved her glycaemic control. Considering the complexity of her case, we explored how she achieved these changes. A GSD-trained nurse delivered the intervention, which involves reflection sheets and advanced professional communication. Glycated hemoglobin was reported in the patient's record and an interview conducted by external interviewers was analysed thematically, indicating that a four-stage process of empowerment had taken place: 'focusing on life prior to numbers', 'unpacking a heavy burden', 'breaking out of isolation through communication' and 'finding strength within oneself'. The article emphasises that GSD works by breaking isolation through communication as an appropriate way to achieve good diabetes control. PMID- 26150633 TI - Diagnosis of button battery ingestion by 'halo' radiographic sign: an exception to the rule. PMID- 26150634 TI - An atypical presentation of a typical pulmonary pathogen in an immunosuppressed patient. AB - We describe a case of a 38-year-old, HIV-positive asthmatic man with a history of intravenous methamphetamine substance misuse who presented with worsening dyspnoea, wheeze, productive cough without haemoptysis and deteriorating exercise tolerance. His chest X-ray was clear and subsequent CT scanning demonstrated multilobar, patchy consolidation and ground glass change in the lung parenchyma. His CD4 count was 864 cells/mm(3) (n=500-1500 cells/mm(3)) and viral load 863 IU/mL. Our primary diagnosis was an atypical pneumonia with associated bronchospasm. The differential diagnosis also included a methamphetamine-induced pulmonary haemorrhage, given the multiple small foci of ground glass change. The patient's sputum cultured Haemophilus influenzae, which was somewhat surprising, given his unusual CT findings. He recovered with antibiotic therapy and a follow up CT scan at 6 weeks revealed complete resolution of the radiological findings. PMID- 26150635 TI - Thrombotic popliteal block following simultaneous bi-cruciate single-stage arthroscopic reconstruction in a neglected multiligamentous knee injury in a smoker. AB - We report a case of neglected multiligamentous injury that developed a complete thrombotic popliteal artery block following arthroscopic surgery. A 56-year-old man, a farmer, presented with an 8-month history of instability of the right knee. Examination revealed ipsilateral anterior (ACL)/posterior cruciate ligament (PCL) injuries. MRI and diagnostic arthroscopy confirmed complete ACL/PCL tear. Single-stage arthroscopic ACL/PCL reconstruction was performed. Postsurgery, the operated limb appeared swollen, firm and cold, without sensation or toe movement. Angiogram revealed complete thrombotic block of left popliteal artery. Fogarty's catheterism was performed and distal vascularity re-established. At 28 months, the patient was back at work with good functional outcome. We failed to examine the patient preoperatively in spite of his advanced age, history of beedi smoking and tobacco use, and presence of feeble vascular pulsations with thickened skin over leg and foot. Thus, in multiligamentous injuries, patient selection and thorough detailed clinical examination are the keys to successful arthroscopic procedures. PMID- 26150636 TI - Pilonidal sinus involving the nasal bridge: a rare manifestation. AB - Pilonidal sinus is very commonly associated with the sacrococcygeal area, but its presence within the head and neck is still unknown to many. Once diagnosed, it is easy to treat and should, therefore, be kept in mind as a possibility when coming across a discharging sinus swelling. We share our experience of two cases of pilonidal sinus presenting over the nasal bridge and their management. PMID- 26150637 TI - Primary colonic adenocarcinoma diagnosed with cutaneous shave biopsy. AB - A 67-year-old man presented to the emergency department with chronic weakness, fatigue and failure to thrive. On physical examination, he was found to have multifocal exophytic cutaneous masses in the pubic and scrotal regions. We obtained a shave biopsy, and subsequent histopathology demonstrated non-native tissue consistent with metastasis from a primary adenocarcinoma. We report this novel case of anogenital cutaneous metastases of colorectal adenocarcinoma. PMID- 26150638 TI - Dysphagia, dysphonia and sore throat following cerebral infarction: an unexpected cause. AB - A 75-year-old woman presented with left-sided weakness. There was no speech disturbance or reported swallowing difficulties. CT of the head revealed infarction in the territory of the right middle cerebral artery. The patient was transferred to the acute stroke unit and a nasogastric tube was placed following a failed swallow screening test. The following day, on assessment, there was considerable pain on swallowing. The tone and quality of the patient's voice had deteriorated and there was significant dysphagia. Seven days later a plastic item, later identified as the patient's denture, was expectorated. Following this, the dysphagia, dysphonia and sore throat rapidly resolved. The case highlights the importance of considering foreign body in the differential, and oral cavity examination in the assessment of a patient with dysphagia and sore throat is essential. PMID- 26150639 TI - Clostridium difficile infection after ileostomy closure mimicking anastomotic leak. AB - Clostridium difficile infection is linked to antibiotic exposure, with elderly and immunocompromised hospitalised patients being particularly at risk. The symptoms range from mild diarrhoea to life-threatening fulminant colitis. We describe an unusual presentation of C. difficile infection after closure of ileostomy in a healthy 60-year-old man with a history of low anterior resection and defunctioning ileostomy for rectal tumour. On the third day postoperatively, the patient developed left lower abdominal pain and profuse diarrhoea. With worsening symptoms and steadily increasing inflammatory markers over the following few days, concerns were raised about an anastomotic leak with pelvic abscess. CT of the abdomen/pelvis on day 7 surprisingly showed colitis in the neorectum/sigmoid colon. A stool test confirmed C. difficile infection. PMID- 26150640 TI - An intracardial mass in a young Syrian refugee. AB - A 35-year-old previously healthy man presented with orogenital ulcerations, high fever, weight loss and leg thrombosis. Antibiotics were ineffective. His symptoms persisted and 3 years later he suffered from exertional dyspnoea. Inflammatory markers were elevated and all cultures were negative. CT of the thorax showed bilateral pulmonary embolism and a mass attached to the septum of the right ventricle, as well as an occluded vena cava inferior. Histology of the cardiac mass revealed a thrombus. The pulmonary embolisation progressed despite treatment with full-dose dalteparin. After being diagnosed with Behcet's disease, a multisystemic large-vessel vasculitis, and treated with high-dose prednisolone and cyclophosphamide, his ulcerations and his symptoms of dyspnoea disappeared. PMID- 26150641 TI - Maxillary fungal sinusitis secondary to extrusion of endodontic gutta percha points. PMID- 26150642 TI - A severe case of vasoplegic shock following metformin overdose successfully treated with methylene blue as a last line therapy. AB - A 44-year-old man presented to hospital 24 h after an intentional overdose of metformin and gliclazide. He had a critical metabolic acidosis on presentation with a pH of 6.88, and very rapidly deteriorated into distributive shock refractory to large volume fluid resuscitation and massive doses of vasopressors. We introduced a methylene blue infusion as a rescue therapy in an attempt to improve the patient's haemodynamics, which was successful. The patient made a full recovery with no long-term sequelae. PMID- 26150643 TI - A mimic's imitator: a cavitary pneumonia in a myasthenic patient with history of tuberculosis. AB - A 77-year-old man with myasthenia gravis receiving prednisone and plasmapheresis was found to have right upper lobe cavitary pneumonia on radiological imaging studies after thymectomy. He had a remote history of treated pulmonary tuberculosis (TB) at the age of 19. On the basis of history of TB and current prednisone therapy, reactivation of pulmonary TB was highly suspected. Branching Gram-positive bacilli were identified on bronchoalveolar lavage (BAL). BAL Ziehl Neelsen Acid-fast bacilli stain was negative, but a modified Kinyoun stain revealed branching, beaded, filamentous bacilli, suggestive of Nocardia spp. Nocardia cyriacigeorgica grew from the BAL culture. Cerebral MRI demonstrated a right frontal lobe lesion, clinically correlated to be nocardial brain abscess. The patient was treated with three-drug antimicrobial therapy (trimethoprim sulfamethoxazole, meropenem, linezolid) for 2 months, followed by an additional 10 months of trimethoprim-sulfamethoxazole. Amikacin would have been included in the initial three-drug regimen, but its use was contraindicated in our myasthenic patient because aminoglycoside would trigger fatal myasthenic crisis by neuromuscular blockage. Follow-up imaging studies revealed resolution of the lung and brain lesions. PMID- 26150644 TI - Old complication, new presentation: a case of the spleen taking the bullet. AB - We report a case of a 43-year-old man who presented to the accident and emergency department with acute abdominal pain. Ultrasound investigation showed non specific splenic pathology and treatment for a splenic abscess was started. The patient later described a history of episodic, cardiac-sounding chest pain occurring at rest, the most recent case of which (6 days prior to admission) had been unusually severe. ECG showed anterior Q waves and aneurysm-type ST-T segment changes. Echocardiography, coupled with a CT scan of the abdomen, revealed the aetiology. The patient had sustained an anterolateral myocardial infarction, which had led to mural thrombus formation and secondary embolisation to the spleen, with no other end organ damage detected. The patient responded well to conservative management of the splenic infarct and initiation on the acute coronary syndrome pathway. Coronary angiography showed mild disease of the proximal left anterior descending artery. Cardiac MRI at 1 month confirmed an ischaemic aetiology. PMID- 26150645 TI - Isolated scaphoid fracture with palmar dislocation of the proximal fragment. PMID- 26150646 TI - Adult-onset Still's disease in a Nigerian woman. AB - Adult-onset Still's disease (AOSD) is an uncommon systemic inflammatory disorder of unknown aetiology. Although there have been reports and series elsewhere, there have been very few such reports on black Africans. The rarity of the reporting of this disease has been associated with a low index of suspicion and hence delayed diagnosis in patients suffering from it. We report a case of a 28 year-old woman, a teacher, who had been repeatedly treated for malarial fever over a 2-month period. She was also briefly managed elsewhere for systemic lupus erythematosus due to a persistent fever with associated polyarthralgia, sore throat, rash and high erythrocyte sedimentation rate. On presentation to our facility, she fulfilled the Yamaguchi criteria for AOSD and had a markedly elevated serum ferritin level. She was successfully managed with etanercept and methotrexate. This is the first report of AOSD from Nigeria. PMID- 26150647 TI - Peeling skin syndrome. PMID- 26150648 TI - Thyroglossal duct cyst carcinoma: diagnostic and management considerations in a 15-year-old with a large submental mass. AB - A 15-year old boy presented with a 2-year history of a painless slowly enlarging submental neck mass. Head and neck imaging showed a multicystic mass with a central solid component that was closely applied to the hyoid bone. Core needle biopsy under general anaesthesia revealed a papillary thyroid neoplasm. The mass was resected and frozen section histology confirmed papillary carcinoma. Intraoperatively, enlarged cervical lymph nodes were palpable. Bilateral neck dissections and total thyroidectomy with parathyroid reimplantation were performed. On histological examination, the thyroid gland was not involved. The patient recovered uneventfully from the surgery and is planned for radioactive iodine therapy and thyroxine suppression, with subsequent follow-up with serum thyroid-stimulating hormone and thyroglobulin for surveillance. We review the literature and discuss challenges in the diagnosis and surgical management of this rare entity in the paediatric age group. PMID- 26150649 TI - Chronic subclinical perforation of a duodenal ulcer presenting with an abdominal abscess in a patient with seronegative rheumatoid arthritis. AB - Peptic ulcer disease has been a major problem since the turn of this century with high morbidity and mortality. Perforation is less common, with an estimated incidence of 7-10 per 100 000. We present a young woman with rheumatoid arthritis presenting with anaemia. On work up, she was found to have a chronic abdominal abscess secondary to subclinical perforation of a duodenal ulcer. After undergoing percutaneous drainage, she became haemodynamically unstable and was taken for surgical washout and jejunostomy tube placement. A week later she had a decrease in the size of the abscess and was discharged home with drain and tube feeds. At her follow-up a few weeks later, she was tolerating goal tube feeds. PMID- 26150650 TI - Single colonic metastasis from breast cancer 11 years after mastectomy. PMID- 26150651 TI - Facial asymmetry in crying newborn. PMID- 26150652 TI - Spontaneous right-sided ureterocolic fistula: a rare complication of colonic diverticular disease. PMID- 26150653 TI - Benign renal schwannoma: a rare entity. PMID- 26150654 TI - The within-host dynamics of African trypanosome infections. AB - African trypanosomes are single-celled protozoan parasites that are capable of long-term survival while living extracellularly in the bloodstream and tissues of mammalian hosts. Prolonged infections are possible because trypanosomes undergo antigenic variation-the expression of a large repertoire of antigenically distinct surface coats, which allows the parasite population to evade antibody mediated elimination. The mechanisms by which antigen genes become activated influence their order of expression, most likely by influencing the frequency of productive antigen switching, which in turn is likely to contribute to infection chronicity. Superimposed upon antigen switching as a contributor to trypanosome infection dynamics is the density-dependent production of cell-cycle arrested parasite transmission stages, which limit the infection while ensuring parasite spread to new hosts via the bite of blood-feeding tsetse flies. Neither antigen switching nor developmental progression to transmission stages is driven by the host. However, the host can contribute to the infection dynamic through the selection of distinct antigen types, the influence of genetic susceptibility or trypanotolerance and the potential influence of host-dependent effects on parasite virulence, development of transmission stages and pathogenicity. In a zoonotic infection cycle where trypanosomes circulate within a range of host animal populations, and in some cases humans, there is considerable scope for a complex interplay between parasite immune evasion, transmission potential and host factors to govern the profile and outcome of infection. PMID- 26150655 TI - How is the effectiveness of immune surveillance impacted by the spatial distribution of spreading infections? AB - What effect does the spatial distribution of infected cells have on the efficiency of their removal by immune cells, such as cytotoxic T lymphocytes (CTL)? If infected cells spread in clusters, CTL may initially be slow to locate them but subsequently kill more rapidly than in diffuse infections. We address this question using stochastic, spatially explicit models of CTL interacting with different patterns of infection. Rather than the effector : target ratio, we show that the relevant quantity is the ratio of a CTL's expected time to locate its next target (search time) to the average time it spends conjugated with a target that it is killing (handling time). For inefficient (slow) CTL, when the search time is always limiting, the critical density of CTL (that required to control 50% of infections, C(*)) is independent of the spatial distribution and derives from simple mass-action kinetics. For more efficient CTL such that handling time becomes limiting, mass-action underestimates C(*), and the more clustered an infection the greater is C(*). If CTL migrate chemotactically towards targets the converse holds-C(*) falls, and clustered infections are controlled most efficiently. Real infections are likely to spread patchily; this combined with even weak chemotaxis means that sterilizing immunity may be achieved with substantially lower numbers of CTL than standard models predict. PMID- 26150656 TI - Effects of neutralizing antibodies on escape from CD8+ T-cell responses in HIV-1 infection. AB - Despite substantial advances in our knowledge of immune responses against HIV-1 and of its evolution within the host, it remains unclear why control of the virus eventually breaks down. Here, we present a new theoretical framework for the infection dynamics of HIV-1 that combines antibody and CD8(+) T-cell responses, notably taking into account their different lifespans. Several apparent paradoxes in HIV pathogenesis and genetics of host susceptibility can be reconciled within this framework by assigning a crucial role to antibody responses in the control of viraemia. We argue that, although escape from or progressive loss of quality of CD8(+) T-cell responses can accelerate disease progression, the underlying cause of the breakdown of virus control is the loss of antibody induction due to depletion of CD4(+) T cells. Furthermore, strong antibody responses can prevent CD8(+) T-cell escape from occurring for an extended period, even in the presence of highly efficacious CD8(+) T-cell responses. PMID- 26150657 TI - Estimating T-cell repertoire diversity: limitations of classical estimators and a new approach. AB - A highly diverse T-cell receptor (TCR) repertoire is a fundamental property of an effective immune system, and is associated with efficient control of viral infections and other pathogens. However, direct measurement of total TCR diversity is impossible. The diversity is high and the frequency distribution of individual TCRs is heavily skewed; the diversity therefore cannot be captured in a blood sample. Consequently, estimators of the total number of TCR clonotypes that are present in the individual, in addition to those observed, are essential. This is analogous to the 'unseen species problem' in ecology. We review the diversity (species richness) estimators that have been applied to T-cell repertoires and the methods used to validate these estimators. We show that existing approaches have significant shortcomings, and frequently underestimate true TCR diversity. We highlight our recently developed estimator, DivE, which can accurately estimate diversity across a range of immunological and biological systems. PMID- 26150658 TI - Evaluating the within-host fitness effects of mutations fixed during virus adaptation to different ecotypes of a new host. AB - The existence of genetic variation for resistance in host populations is assumed to be essential to the spread of an emerging virus. Models predict that the rate of spread slows down with the increasing frequency and higher diversity of resistance alleles in the host population. We have been using the experimental pathosystem Arabidopsis thaliana-tobacco etch potyvirus (TEV) to explore the interplay between genetic variation in host's susceptibility and virus diversity. We have recently shown that TEV populations evolving in A. thaliana ecotypes that differ in susceptibility to infection gained within-host fitness, virulence and infectivity in a manner compatible with a gene-for-gene model of host-parasite interactions: hard-to-infect ecotypes were infected by generalist viruses, whereas easy-to-infect ecotypes were infected by every virus. We characterized the genomes of the evolved viruses and found cases of host-driven convergent mutations. To gain further insights in the mechanistic basis of this gene-for gene model, we have generated all viral mutations individually as well as in specific combinations and tested their within-host fitness effects across ecotypes. Most of these mutations were deleterious or neutral in their local ecotype and only a very reduced number had a host-specific beneficial effect. We conclude that most of the mutations fixed during the evolution experiment were so by drift or by selective sweeps along with the selected driver mutation. In addition, we evaluated the ruggedness of the underlying adaptive fitness landscape and found that mutational effects were mostly multiplicative, with few cases of significant epistasis. PMID- 26150659 TI - Within-host competition between Borrelia afzelii ospC strains in wild hosts as revealed by massively parallel amplicon sequencing. AB - Infections frequently consist of more than one strain of a given pathogen. Experiments have shown that co-infecting strains often compete, so that the infection intensity of each strain in mixed infections is lower than in single strain infections. Such within-host competition can have important epidemiological and evolutionary consequences. However, the extent of competition has rarely been investigated in wild, naturally infected hosts, where there is noise in the form of varying inoculation doses, asynchronous infections and host heterogeneity, which can potentially alleviate or eliminate competition. Here, we investigated the extent of competition between Borrelia afzelii strains (as determined by ospC genotype) in three host species sampled in the wild. For this purpose, we developed a protocol for 454 amplicon sequencing of ospC, which allows both detection and quantification of each individual strain in an infection. Each host individual was infected with one to six ospC strains. The infection intensity of each strain was lower in mixed infections than in single ones, showing that there was competition. Rank-abundance plots revealed that there was typically one dominant strain, but that the evenness of the relative infection intensity of the different strains in an infection increased with the multiplicity of infection. We conclude that within-host competition can play an important role under natural conditions despite many potential sources of noise, and that quantification by next-generation amplicon sequencing offers new possibilities to dissect within-host interactions in naturally infected hosts. PMID- 26150661 TI - Interactions between multiple helminths and the gut microbiota in wild rodents. AB - The gut microbiota is vital to host health and, as such, it is important to elucidate the mechanisms altering its composition and diversity. Intestinal helminths are host immunomodulators and have evolved both temporally and spatially in close association with the gut microbiota, resulting in potential mechanistic interplay. Host-helminth and host-microbiota interactions are comparatively well-examined, unlike microbiota-helminth relationships, which typically focus on experimental infection with a single helminth species in laboratory animals. Here, in addition to a review of the literature on helminth microbiota interactions, we examined empirically the association between microbiota diversity and composition and natural infection of multiple helminth species in wild mice (Apodemus flavicollis), using 16S rRNA gene catalogues (metataxonomics). In general, helminth presence is linked with high microbiota diversity, which may confer health benefits to the host. Within our wild rodent system variation in the composition and abundance of gut microbial taxa associated with helminths was specific to each helminth species and occurred both up- and downstream of a given helminth's niche (gut position). The most pronounced helminth-microbiota association was between the presence of tapeworms in the small intestine and increased S24-7 (Bacteroidetes) family in the stomach. Helminths clearly have the potential to alter gut homeostasis. Free-living rodents with a diverse helminth community offer a useful model system that enables both correlative (this study) and manipulative inference to elucidate helminth-microbiota interactions. PMID- 26150660 TI - The role of the local microbial ecosystem in respiratory health and disease. AB - Respiratory tract infections are a major global health concern, accounting for high morbidity and mortality, especially in young children and elderly individuals. Traditionally, highly common bacterial respiratory tract infections, including otitis media and pneumonia, were thought to be caused by a limited number of pathogens including Streptococcus pneumoniae and Haemophilus influenzae. However, these pathogens are also frequently observed commensal residents of the upper respiratory tract (URT) and form-together with harmless commensal bacteria, viruses and fungi-intricate ecological networks, collectively known as the 'microbiome'. Analogous to the gut microbiome, the respiratory microbiome at equilibrium is thought to be beneficial to the host by priming the immune system and providing colonization resistance, while an imbalanced ecosystem might predispose to bacterial overgrowth and development of respiratory infections. We postulate that specific ecological perturbations of the bacterial communities in the URT can occur in response to various lifestyle or environmental effectors, leading to diminished colonization resistance, loss of containment of newly acquired or resident pathogens, preluding bacterial overgrowth, ultimately resulting in local or systemic bacterial infections. Here, we review the current body of literature regarding niche-specific upper respiratory microbiota profiles within human hosts and the changes occurring within these profiles that are associated with respiratory infections. PMID- 26150662 TI - Suppression of inflammation by helminths: a role for the gut microbiota? AB - Multiple recent investigations have highlighted the promise of helminth-based therapies for the treatment of inflammatory disorders of the intestinal tract of humans, including inflammatory bowel disease and coeliac disease. However, the mechanisms by which helminths regulate immune responses, leading to the amelioration of symptoms of chronic inflammation are unknown. Given the pivotal roles of the intestinal microbiota in the pathogenesis of these disorders, it has been hypothesized that helminth-induced modifications of the gut commensal flora may be responsible for the therapeutic properties of gastrointestinal parasites. In this article, we review recent progress in the elucidation of host-parasite microbiota interactions in both animal models of chronic inflammation and humans, and provide a working hypothesis of the role of the gut microbiota in helminth induced suppression of inflammation. PMID- 26150663 TI - The evolution of bacterial resistance against bacteriophages in the horse chestnut phyllosphere is general across both space and time. AB - Insight to the spatial and temporal scales of coevolution is key to predicting the outcome of host-parasite interactions and spread of disease. For bacteria infecting long-lived hosts, selection to overcome host defences is just one factor shaping the course of evolution; populations will also be competing with other microbial species and will themselves be facing infection by bacteriophage viruses. Here, we examine the temporal and spatial patterns of bacterial adaptation against natural phage populations from within leaves of horse chestnut trees. Using a time-shift experiment with both sympatric and allopatric phages from either contemporary or earlier points in the season, we demonstrate that bacterial resistance is higher against phages from the past, regardless of spatial sympatry or how much earlier in the season phages were collected. Similarly, we show that future bacterial hosts are more resistant to both sympatric and allopatric phages than contemporary bacterial hosts. Together, our results suggest the evolution of relatively general bacterial resistance against phages in nature and are contrasting to previously observed patterns of phage adaptation to bacteria from the same tree hosts over the same time frame, indicating a potential asymmetry in coevolutionary dynamics. PMID- 26150664 TI - Building the microbiome in health and disease: niche construction and social conflict in bacteria. AB - Microbes collectively shape their environment in remarkable ways via the products of their metabolism. The diverse environmental impacts of macro-organisms have been collated and reviewed under the banner of 'niche construction'. Here, we identify and review a series of broad and overlapping classes of bacterial niche construction, ranging from biofilm production to detoxification or release of toxins, enzymes, metabolites and viruses, and review their role in shaping microbiome composition, human health and disease. Some bacterial niche constructing traits can be seen as extended phenotypes, where individuals actively tailor their environment to their benefit (and potentially to the benefit of others, generating social dilemmas). Other modifications can be viewed as non-adaptive by-products from a producer perspective, yet they may lead to remarkable within-host environmental changes. We illustrate how social evolution and niche construction perspectives offer complementary insights into the dynamics and consequences of these traits across distinct timescales. This review highlights that by understanding the coupled bacterial and biochemical dynamics in human health and disease we can better manage host health. PMID- 26150665 TI - The tortoise or the hare? Impacts of within-host dynamics on transmission success of arthropod-borne viruses. AB - Arthropod-borne viruses (arboviruses) are maintained in a cycle of alternating transmission between vertebrate hosts and arthropod vectors. Arboviruses possess RNA genomes capable of rapid diversification and adaptation, and the between-host trade-offs inherent to host alternation impose well-documented constraints on arbovirus evolution. Here, we investigate the less well-studied within-host trade offs that shape arbovirus replication dynamics and transmission. Arboviruses generally establish lifelong infection in vectors but transient infection of variable magnitude (i.e. peak virus concentration) and duration in vertebrate hosts. In the majority of experimental infections of vertebrate hosts, both the magnitude and duration of arbovirus replication depended upon the dose of virus administered, with increasing dose resulting in greater magnitude but shorter duration of viraemia. This pattern suggests that the vertebrate immune response imposes a trade-off between the height and breadth of the virus replication curve. To investigate the impact of this trade-off on transmission, we used a simple modelling approach to contrast the effect of 'tortoise' (low magnitude, long duration viraemia) and 'hare' (high magnitude, short duration viraemia) arbovirus replication strategies on transmission. This model revealed that, counter to previous theory, arboviruses that adopt a tortoise strategy have higher rates of persistence in both host and vector populations. PMID- 26150666 TI - Avian malaria: a new lease of life for an old experimental model to study the evolutionary ecology of Plasmodium. AB - Avian malaria has historically played an important role as a model in the study of human malaria, being a stimulus for the development of medical parasitology. Avian malaria has recently come back to the research scene as a unique animal model to understand the ecology and evolution of the disease, both in the field and in the laboratory. Avian malaria is highly prevalent in birds and mosquitoes around the world and is amenable to laboratory experimentation at each stage of the parasite's life cycle. Here, we take stock of 5 years of experimental laboratory research carried out using Plasmodium relictum SGS1, the most prevalent avian malaria lineage in Europe, and its natural vector, the mosquito Culex pipiens. For this purpose, we compile and analyse data obtained in our laboratory in 14 different experiments. We provide statistical relationships between different infection-related parameters, including parasitaemia, gametocytaemia, host morbidity (anaemia) and transmission rates to mosquitoes. This analysis provides a wide-ranging picture of the within-host and between-host parameters that may bear on malaria transmission and epidemiology. PMID- 26150667 TI - Within-host competitive interactions as a mechanism for the maintenance of parasite diversity. AB - Variation among parasite strains can affect the progression of disease or the effectiveness of treatment. What maintains parasite diversity? Here I argue that competition among parasites within the host is a major cause of variation among parasites. The competitive environment within the host can vary depending on the parasite genotypes present. For example, parasite strategies that target specific competitors, such as bacteriocins, are dependent on the presence and susceptibility of those competitors for success. Accordingly, which parasite traits are favoured by within-host selection can vary from host to host. Given the fluctuating fitness landscape across hosts, genotype by genotype (G*G) interactions among parasites should be prevalent. Moreover, selection should vary in a frequency-dependent manner, as attacking genotypes select for resistance and genotypes producing public goods select for cheaters. I review competitive coexistence theory with regard to parasites and highlight a few key examples where within-host competition promotes diversity. Finally, I discuss how within host competition affects host health and our ability to successfully treat infectious diseases. PMID- 26150669 TI - From within-host interactions to epidemiological competition: a general model for multiple infections. AB - Many hosts are infected by several parasite genotypes at a time. In these co infected hosts, parasites can interact in various ways thus creating diverse within-host dynamics, making it difficult to predict the expression and the evolution of virulence. Moreover, multiple infections generate a combinatorial diversity of cotransmission routes at the host population level, which complicates the epidemiology and may lead to non-trivial outcomes. We introduce a new model for multiple infections, which allows any number of parasite genotypes to infect hosts and potentially coexist in the population. In our model, parasites affect one another's within-host growth through density-dependent interactions and by means of public goods and spite. These within-host interactions determine virulence, recovery and transmission rates, which are then integrated in a transmission network. We use analytical solutions and numerical simulations to investigate epidemiological feedbacks in host populations infected by several parasite genotypes. Finally, we discuss general perspectives on multiple infections. PMID- 26150668 TI - Crossing the scale from within-host infection dynamics to between-host transmission fitness: a discussion of current assumptions and knowledge. AB - The progression of an infection within a host determines the ability of a pathogen to transmit to new hosts and to maintain itself in the population. While the general connection between the infection dynamics within a host and the population-level transmission dynamics of pathogens is widely acknowledged, a comprehensive and quantitative understanding that would allow full integration of the two scales is still lacking. Here, we provide a brief discussion of both models and data that have attempted to provide quantitative mappings from within host infection dynamics to transmission fitness. We present a conceptual framework and provide examples of studies that have taken first steps towards development of a quantitative framework that scales from within-host infections to population-level fitness of different pathogens. We hope to illustrate some general themes, summarize some of the recent advances and-maybe most importantly discuss gaps in our ability to bridge these scales, and to stimulate future research on this important topic. PMID- 26150670 TI - Within-host dynamics of infection: from ecological insights to evolutionary predictions. PMID- 26150672 TI - A look inside the arteries: moving from event rates to subclinical measures of disease. PMID- 26150671 TI - Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study. AB - OBJECTIVES: Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. METHODS: At enrolment (1993-1997), spouses provided information about ever use of specific pesticides, including 10 OPs, demographic information, reproductive health history and other potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% CIs for all cancers diagnosed through 2010 for North Carolina and through 2011 for Iowa. RESULTS: Among 30,003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43). CONCLUSIONS: We observed increased risk with OP use for several hormonally related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation. PMID- 26150673 TI - The effectiveness of using the workplace to identify and address modifiable health risk factors in deprived populations. AB - OBJECTIVES: To establish whether a programme of targeted health screening, with referral to appropriate interventions, offered to an employed but socioeconomically deprived group was effective in overcoming barriers to uptake of such services and improving a range of surrogate health markers for participants. METHODS: Low-paid local government employees from socially and economically deprived areas in North-East England were invited to attend a free health check. Health checks were conducted within working hours and close to their worksite, and included assessment of a range of lifestyle and health related risk factors, including those associated with cardiovascular disease (CVD). A range of additional interventions were offered where indicated. Participants were invited to repeat screening approximately 9 months later. RESULTS: 635 (20% response rate) employees in the target age group (>=40 years) attended the first check. Most health risk markers improved in those (N=427) attending both health checks, as did the mean CVD risk score (t=2.86, p=0.004). 269 referrals were made to the intervention programmes. CONCLUSIONS: This workplace programme had a positive impact on cardiovascular health, but attendance rates were low. These findings suggest that workplace health screening activities may have the potential to improve health in a group often considered hard to reach by other routes, but do not offer a straightforward solution in overcoming barriers to access for such subgroups within the working population. PMID- 26150675 TI - Quality control review: implementing a scientifically based quality control system. AB - This review focuses on statistical quality control in the context of a quality management system. It describes the use of a 'Sigma-metric' for validating the performance of a new examination procedure, developing a total quality control strategy, selecting a statistical quality control procedure and monitoring ongoing quality on the sigma scale. Acceptable method performance is a prerequisite to the design and implementation of statistical quality control procedures. Statistical quality control can only monitor performance, and when properly designed, alert analysts to the presence of additional errors that occur because of unstable performance. A new statistical quality control planning tool, called 'Westgard Sigma Rules,' provides a simple and quick way for selecting control rules and the number of control measurements needed to detect medically important errors. The concept of a quality control plan is described, along with alternative adaptations of a total quality control plan and a risk-based individualized quality control plan. Finally, the ongoing monitoring of analytic performance and test quality are discussed, including determination of measurement uncertainty from statistical quality control data collected under intermediate precision conditions and bias determined from proficiency testing/external quality assessment surveys. A new graphical tool, called the Sigma Quality Assessment Chart, is recommended for demonstrating the quality of current examination procedures on the sigma scale. PMID- 26150674 TI - Psychometric Properties of "Community Assessment of Psychic Experiences": Review and Meta-analyses. AB - The Community Assessment of Psychic Experiences (CAPE) has been used extensively as a measurement for psychosis proneness in clinical and research settings. However, no prior review and meta-analysis have comprehensively examined psychometric properties (reliability and validity) of CAPE scores across different studies. To study CAPE's internal reliability--ie, how well scale items correlate with one another--111 studies were reviewed. Of these, 18 reported unique internal reliability coefficients using data at hand, which were aggregated in a meta-analysis. Furthermore, to confirm the number and nature of factors tapped by CAPE, 17 factor analytic studies were reviewed and subjected to meta-analysis in cases of discrepancy. Results suggested that CAPE scores were psychometrically reliable--ie, scores obtained could be attributed to true score variance. Our review of factor analytic studies supported a 3-factor model for CAPE consisting of "Positive", "Negative", and "Depressive" subscales; and a tripartite structure for the Negative dimension consisting of "Social withdrawal", "Affective flattening", and "Avolition" subdimensions. Meta-analysis of factor analytic studies of the Positive dimension revealed a tridimensional structure consisting of "Bizarre experiences", "Delusional ideations", and "Perceptual anomalies". Information on reliability and validity of CAPE scores is important for ensuring accurate measurement of the psychosis proneness phenotype, which in turn facilitates early detection and intervention for psychotic disorders. Apart from enhancing the understanding of psychometric properties of CAPE scores, our review revealed questionable reporting practices possibly reflecting insufficient understanding regarding the significance of psychometric properties. We recommend increased focus on psychometrics in psychology programmes and clinical journals. PMID- 26150676 TI - Clinical implications of pleural effusion in patients with acute type B aortic dissection. AB - BACKGROUND: Pleural effusion may complicate acute Stanford type B aortic dissection (ABAD). AIMS: To identify the relationships between the quantity and side of the pleural effusion, biomarkers and outcomes in patients with ABAD. METHODS: We undertook a retrospective review of 105 patients with ABAD. Their demographics, the data on admission and during hospital stay, the volume of pleural effusion calculated from the area on computed tomography images and clinical outcomes were analysed. RESULTS: The median estimated peak volume (median 6.7 days after onset) was 129 ml (63-192, range 26-514 ml) on the left and 11 ml (6-43, range 2-300 ml) on the right. On univariate analysis, the volume of bilateral effusions was associated with anaemia, hypoalbuminaemia and inflammatory markers, whereas the volume of left-sided effusions was associated with older age, low diastolic blood pressure and maximum aortic diameter. Multivariate analysis revealed that hypoalbuminaemia was independently associated with bilateral effusion volume ( P<0.001), while maximum aortic diameter was associated with left-sided effusion volume ( P=0.019). A greater volume of bilateral plural effusion was associated with longer intensive care unit stay. CONCLUSIONS: Larger bilateral pleural effusions in patients with ABAD were associated with hypoalbuminaemia and potentially with anaemia and inflammation, and may increase the length of intensive care unit stay. Left-sided effusion volume appears to be influenced by the nature of the aortic dilatation. Multiple mechanisms may underpin the development of pleural effusion in ABAD, and are likely to influence clinical outcomes. PMID- 26150677 TI - Predictors of Intention to Refer to Pediatric Palliative or Hospice Care. AB - The purpose of this descriptive correlational study was to determine whether nurse characteristics, level of comfort with care of the dying, and spirituality predict intention to refer and timing of referral to pediatric palliative/hospice care. The Behavioral Model of Health Services Use served as the framework for this study. Data were collected from 105 pediatric nurses recruited from 7 patient units of one pediatric hospital. Regression analysis revealed several nurse factors (practice unit, years of experience, age, race/ethnicity) that predicted intent to refer and timing of referral to pediatric palliative/hospice care. The relationship between nurse characteristics and intent to refer was specific to certain medical conditions (HIV, extreme prematurity, brain injuries). Healthcare providers can use these findings to improve care for children with life-limiting illnesses. PMID- 26150678 TI - Naloxegol: A Novel Therapy in the Management of Opioid-Induced Constipation. AB - Opioid-related bowel dysfunction is a common and potentially severe adverse effect from treatment with opioid analgesics. Its development is not dose related, nor do patients develop tolerance. Opioid-induced constipation (OIC) can lead to fecal impaction, bowel obstruction, and bowel perforation as well as noncompliance with opioid analgesics and poor quality of life. Routine administration of laxatives is necessary to maintain bowel function, and, in refractory cases, other modalities must be pursued. Available options are limited but include peripherally acting MU-opioid receptor antagonists (PAMORAs), including methylnaltrexone. Naloxegol is a newly developed PAMORA that is available through the oral route. At the therapeutic dose of 25 mg daily, naloxegol is effective and safe, with a limited side effect profile and is associated with preservation of centrally mediated analgesia. In this article, we discuss the pharmacokinetics, pharmacodynamics, adverse effects, clinical trials, and cost considerations of naloxegol. Finally, we discuss its potential role as a novel key treatment for OIC in palliative medicine patients. PMID- 26150679 TI - A Method of Speech Periodicity Enhancement Using Transform-domain Signal Decomposition. AB - Periodicity is an important property of speech signals. It is the basis of the signal's fundamental frequency and the pitch of voice, which is crucial to speech communication. This paper presents a novel framework of periodicity enhancement for noisy speech. The enhancement is applied to the linear prediction residual of speech. The residual signal goes through a constant-pitch time warping process and two sequential lapped-frequency transforms, by which the periodic component is concentrated in certain transform coefficients. By emphasizing the respective transform coefficients, periodicity enhancement of noisy residual signal is achieved. The enhanced residual signal and estimated linear prediction filter parameters are used to synthesize the output speech. An adaptive algorithm is proposed for adjusting the weights for the periodic and aperiodic components. Effectiveness of the proposed approach is demonstrated via experimental evaluation. It is observed that harmonic structure of the original speech could be properly restored to improve the perceptual quality of enhanced speech. PMID- 26150680 TI - IMRT, IGRT, and other high technology becomes standard in external beam radiotherapy: But is image-guided brachytherapy for cervical cancer too expensive? PMID- 26150681 TI - A method to improve fluence resolution derived from two-dimensional detector array measurements for patient-specific IMRT verification using the information collected in dynalog files. AB - This paper proposes a method for improving the resolution of the fluence derived from detector array measurement using the information collected in dynalog files. From dynalog information, a file is generated with the actual multileaf collimator (MLC) positions and used as input to the treatment planning system (TPS) to obtain the dynalog-derived fluence and the theoretical response over the detector array. In contrast with the measured response, this theoretical response allows for correction of the dynalog-derived fluence and translation into the reconstructed fluence. This fluence is again introduced into the planning system to verify the treatment using clinical tools. Initially, more than 98% of the points passed the two-dimensional (2D) phantom gamma test (3% local dose - 3 mm) for all of the treatment verifications, but in some dose-volume histogram (DVH) comparisons, we note sensitive differences for the planning target volume (PTV) coverage and for the maximum doses in at-risk organs (up to 3.5%). In dose distribution evaluations, we found differences of up to 5% in the PTV edges in certain cases due to detector array measurement errors. This work improves the resolution of the fluence derived from detector array measurements based on the treatment information, in contrast with the current commercial proposals based on planned data. PMID- 26150682 TI - Monte Carlo-based dose calculation for (32)P patch source for superficial brachytherapy applications. AB - Skin cancer treatment involving (32)P source is an easy, less expensive method of treatment limited to small and superficial lesions of approximately 1 mm deep. Bhabha Atomic Research Centre (BARC) has indigenously developed (32)P nafion based patch source (1 cm * 1 cm) for treating skin cancer. For this source, the values of dose per unit activity at different depths including dose profiles in water are calculated using the EGSnrc-based Monte Carlo code system. For an initial activity of 1 Bq distributed in 1 cm(2) surface area of the source, the calculated central axis depth dose values are 3.62 * 10(-10) GyBq(-1) and 8.41 * 10(-11) GyBq(-1)at 0.0125 and 1 mm depths in water, respectively. Hence, the treatment time calculated for delivering therapeutic dose of 30 Gy at 1 mm depth along the central axis of the source involving 37 MBq activity is about 2.7 hrs. PMID- 26150683 TI - What benefit could be derived from on-line adaptive prostate radiotherapy using rectal diameter as a predictor of motion? AB - This study investigated a relationship between rectum diameter and prostate motion during treatment with a view to reducing planning target volume (PTV) margins for an adaptive protocol. One hundred and ninety-four cone-beam computed tomography (CBCT) images of 10 patients were used to relate rectum diameter on CBCT to prostate intrafraction displacement. A threshold rectum diameter was used to model the impact of an adaptive PTV margin on rectum and bladder dose. Potential dose escalation with a 6 mm uniform margin adaptive protocol was compared to a PTV margin of 10 mm expansion of the clinical target volume (CTV) except 6 mm posterior. Of 194 fractions, 104 had a maximum rectal diameter of <=3.5 cm. The prostate displaced <=4 mm in 102 of those fractions. Changing from a standard to an adaptive PTV margin reduced the volume of rectum receiving 25, 50, 60, and 70 Gy by around 12, 9, 10, and 16%, respectively and bladder by approximately 21, 27, 29, and 35%, respectively. An average dose escalation of 4.2 Gy may be possible with an adaptive prostate radiotherapy protocol. In conclusion, a relationship between the prostate motion and the diameter of the rectum on CBCT potentially could enable daily adaptive radiotherapy which can be implemented from the first fraction. PMID- 26150684 TI - Transition from image intensifier to flat panel detector in interventional cardiology: Impact of radiation dose. AB - Flat panel detector (FPD) technology in interventional cardiology is on the increase due to its varied advantages compared to the conventional image intensifier (II) systems. It is not clear whether FPD imparts lower radiation doses compared to II systems though a few studies support this finding. This study intends to compare radiation doses from II and FPD systems for coronaryangiography (CAG) and Percutaneous Transluminal Coronary Angioplasty (PTCA) performed in a tertiary referral center. Radiation doses were measured using dose area product (DAP) meter from patients who underwent CAG (n = 222) and PTCA (n = 75) performed using FPD angiography system. The DAP values from FPD were compared with earlier reported data using II systems from the same referral center where the study was conducted. The mean DAP values from FPD system for CAG and PTCA were 24.35 and 63.64 Gycm(2) and those from II system were 27.71 and 65.44 Gycm(2). Transition from II to FPD system requires stringent dose optimization strategies right from the initial period of installation. PMID- 26150685 TI - Radiation dose to patients from X-ray radiographic examinations using computed radiography imaging system. AB - The screen-film system is replaced by computed radiography system for recording the images of the patients during X-ray radiography examinations. The change in imaging system requires the re-establishment of the institutional diagnostic reference levels (DRLs) for different types of X-ray examinations conducted at the hospital. For this purpose, patient specific parameters [age, height, weight, body mass index (BMI), object to image distance (OID)] and machine specific parameters (kVp, mAs, distance and field sizes) of 1875 patients during 21 different types of X-ray examinations were recorded for estimating the entrance skin dose (ESD). The ESD for each of these patients were estimated using measured X-ray beam output and the standard value of the back scatter factor. Five number summary was calculated for all the data for their presentation in the Box-Whisker plot, which provides the statistical distribution of the data. The data collected indicates that majorly performed examinations are cervical spine AP, Chest PA and Knee Lat with percentage contributions of 16.05, 16 and 8.27% respectively. The lowest contribution comes from Hip Lat which is about 1.01%. The ratio of measured ESD (maximum to minimum) for these examinations is found to be highest for the cervical spine AP with a value of 50 followed by Thoracic spine AP of 32.36. The ESD ratio for Chest PA, Knee Lat and Lumbar Spine AP are 30.75, 30.4 and 30.2 respectively. The lowest ESD ratio is for Hip Lat which is 2.68. The third quartile values of ESDs are established as the institutional DRLs. The ESD values obtained for 21 different X-ray projections are either comparable or lesser than the reported national/international values. PMID- 26150686 TI - Up-regulation of Bcl-2 expression in cultured human lymphocytes after exposure to low doses of gamma radiation. AB - Lymphocytes have demonstrated complex molecular responses to induced stress by ionizing radiation. Many of these reactions are mediated through modifications in gene expressions, including the genes involved in apoptosis. The primary aim of this study was to assess the effects of low doses of ionizing radiation on the apoptotic genes, expression levels. The secondary goal was to estimate the time effect on the modified gene expression caused by low doses of ionizing radiation. Mononuclear cells in culture were exposed to various dose values ranged from 20 to 100 mGy by gamma rays from a Cobalt-60 source. Samples were taken for gene expression analysis at hours 4, 24, 48, 72, and 168 following to exposure. Expression level of two apoptotic genes; BAX (pro-apoptotic) and Bcl-2 (anti apoptotic) were examined by relative quantitative real-time polymerase chain reaction (PCR), at different time intervals. Radio-sensitivity of peripheral blood mononucleated cells (PBMCs) was measured by the Bcl-2/BAX ratio (as a predictive marker for radio-sensitivity). The non-parametric two independent samples Mann-Whitney U-test were performed to compare means of gene expression. The results of this study revealed that low doses of gamma radiation can induce early down-regulation of the BAX gene of freshly isolated human PBMCs; however, these changes were restored to near normal levels after 168 hours. In most cases, expression of the Bcl-2 anti-apoptotic gene was up-regulated. Four hours following to exposure to low doses of gamma radiation, apoptotic gene expression is modified, this is manifested as adaptive response. Modification of these gene expressions seems to be a principle pathway in the early radioresistance response. In our study, we found that these changes were temporary and faded completely within a week. PMID- 26150687 TI - Effect of anode/filter combination on average glandular dose in mammography. AB - A comparative analysis of the mean glandular doses was conducted in 100 female patients who underwent screening mammography in 2011 and 2013. Siemens Mammomat Novation with the application of the W/Rh anode/filter combination was used in 2011, whereas in 2013 anode/filter combination was Mo/Mo or Mo/Rh. The functioning of mammography was checked and the effectiveness of the automatic exposure control (AEC) system was verified by measuring compensation of changes in the phantom thickness and measuring tube voltage. On the base of exposure parameters, an average glandular dose for each of 100 female patients was estimated. The images obtained by using AEC system had the acceptable threshold contrast visibility irrespective of the applied anode/filter combination. Mean glandular doses in the females, examined with the application of the W/Rh anode/filter combination, were on average 23.6% lower than that of the Mo/Mo or Mo/Rh anode/filter combinations. It is recommended to use a combination of the W/Rh anode /filter which exhibited lower mean glandular doses. PMID- 26150688 TI - Radiological health assessment of natural radioactivity in the vicinity of Obajana cement factory, North Central Nigeria. AB - Measurements of activity concentrations of natural radionuclides in and around Obajana cement factory, North Central Nigeria have been carried out in this study to determine the activity levels of natural radionuclides in different environmental matrices in order to assess the radiological health hazards associated with the use of these matrices by the local population. A low background Pb-shielded gamma spectroscopic counting assembly utilizing NaI (Tl) detector was employed for the measurements. The results show that sediment samples have the highest activity concentrations of all the radionuclides relative to soil, farmland soil, and rock samples. The radium equivalent activity and indoor gamma dose rates together with the corresponding annual effective indoor doses evaluated were found to be lower than their permissible limits. It suffices to say, that contrary to age-long fear of radiation risks to the population in the vicinity of the cement factory, no excessive radiological health hazards either indoors and/or outdoors is envisaged. Therefore, the environmental matrices around the factory could be used without any restrictions. PMID- 26150689 TI - Efficacy and tolerability of bilateral sustained-release dexamethasone intravitreal implants for the treatment of noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion. AB - PURPOSE: To report our experience with bilateral placement of dexamethasone 0.7 mg (DEX) sustained-release intravitreal implant in the management of noninfectious posterior uveitis or macular edema secondary to retinal vein occlusion. METHODS: A retrospective chart review of patients with bilateral noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion who were treated with DEX intravitreal implant was performed. Ocular side effects such as intraocular pressure (IOP), cataract, and tolerability of bilateral injections was reviewed. RESULTS: Twenty-two eyes of eleven patients treated with a total of 32 DEX implants were included. Ten of eleven patients received bilateral implants due to active noninfectious uveitis while the other demonstrated macular edema in both eyes following separate central retinal vein occlusions. Among the patients with bilateral uveitis, the mean interval between DEX implant in the initial eye and the subsequent DEX in the fellow eye was 15.6 days (range 2-71 days). Seven of the ten patients received the second implant in the fellow eye within 8 days of the initial implantation. None of the patients had bilateral implantations on the same day. Seven eyes required reimplantation for recurrence of inflammation (mean interval between first and repeat implantation was 6.00+/-2.39 months). Following single or, in the case of the aforementioned seven eyes, repeat DEX implantation, all 20 uveitic eyes demonstrated clinical and/or angiographic evidence of decreased inflammation in the form of reduction in vitreous cells on slit lamp ophthalmoscopy, macular edema on ophthalmoscopy, or optical coherence tomography and/or disc and vascular leakage on fluorescein angiography. The mean follow-up for all eyes after initial implantation was 23.57 months (range 1-48 months). IOP was significantly higher (P=0.028) at 6 months (16.62 mmHg +/-5.97) but not (P=0.82) at most recent follow up (14.9+/-3.37 mmHg) when compared with baseline (14.68+/-3.02 mmHg). Four eyes (18.2%) required initiation of IOP-lowering medications. During the follow-up period, no eyes underwent filtration or cataract extraction. No serious ocular adverse effects were noted during the follow-up period. CONCLUSION: In patients with bilateral noninfectious posterior uveitis and macular edema secondary to vein occlusion, bilateral injection of DEX intravitreal implant was well tolerated and had an acceptable safety profile. PMID- 26150690 TI - An outbreak of Ralstonia pickettii endophthalmitis following intravitreal methotrexate injection. AB - PURPOSE: To report an outbreak of endophthalmitis in three eyes of two patients following intravitreal methotrexate, caused by Ralstonia pickettii. DESIGN: Retrospective, noncomparative, consecutive case series. METHODS: Medical records and microbiology results of two patients who presented with acute endophthalmitis following intravitreal methotrexate injection in November 2013 were reviewed. RESULTS: Following intravitreal injections, the patients experienced pain and decrease in vision in the affected eye within 24 hours of receiving intravitreal methotrexate injection. The presenting visual acuity in case 1 was 20/50 in the left eye. The presenting visual acuity in case 2 was hand motions in the right eye and counting fingers at 1 m in the left eye. Both the patients received methotrexate prepared in the same manufacturing facility. Both the patients underwent vitreous biopsy and intravitreal injection of vancomycin 1 mg/0.1 mL, amikacin 400 ug/0.1 mL, and dexamethasone 400 ug/0.1 mL. Microbiology cultures from vitreous, and used and unused vials of methotrexate from the same batch grew R. pickettii. After 8 months of follow-up, both the patients had visual acuity 20/60 or better. CONCLUSION: R. pickettii can be rarely associated with outbreak of endophthalmitis. Timely intervention can be associated with good visual outcome in such patients. PMID- 26150691 TI - Causes of uveitis in children without juvenile idiopathic arthritis. AB - BACKGROUND: The purpose of this study was to report the demographics, disease characteristics, treatments, and visual outcomes of pediatric uveitis patients without juvenile idiopathic arthritis managed in a tertiary medical center. METHODS: A retrospective, observational study was performed in pediatric uveitis patients without juvenile idiopathic arthritis and aged 0-18 years, who were seen at the University of Virginia from 1984 to 2014. RESULTS: Thirty-nine pediatric uveitis patients (57 eyes) were identified. The patient population was 51.28% female, 51.28% Caucasian, and 33.33% African American. The mean age at diagnosis was 11.9 years. The mean duration of follow-up was 3.11 years. The mean number of visits to the clinic was 10.41. Of 57 eyes, 31 (54.39%) had anterior uveitis, 12 (21.05%) had intermediate uveitis, nine (15.79%) had posterior uveitis, and five (8.77%) had panuveitis. The leading diagnoses were traumatic uveitis (25.64%), undifferentiated anterior uveitis (17.95%), undifferentiated intermediate uveitis (15.38%), HLA-B27-associated anterior uveitis (7.69%), and herpetic anterior uveitis (7.69%). Systemic associations included sarcoidosis, ulcerative colitis, and psoriatic arthritis (n=3). The most common treatment modalities included local steroids (66.67%), systemic steroids (23.08%), and antimetabolites (20.51%). Ocular hypertension was found in five (12.82%) patients. Ocular surgery was performed in six (15.38%) patients. Mean best-corrected visual acuity (BCVA) at baseline across all anatomical locations was 0.458 logMAR, and was 0.411 logMAR at final follow-up. Mean BCVA improved during follow-up in all but the anterior uveitis group. The mean baseline intraocular pressure was 14.27 mmHg, and was 14.22 mmHg at final follow-up. CONCLUSION: Uveitis in childhood is a vision-threatening group of inflammatory disorders arising from numerous etiologies that vary geographically and historically. Because of the high burden of disease, the difficulty of making precise etiologic diagnoses, and the complicated management, it is imperative that affected children be referred to and closely monitored by uveitis specialists to prevent devastating ocular damage. This study found that BCVA and intraocular pressure did not vary significantly during follow-up, suggesting that close management by an ophthalmologist may prevent adverse visual outcomes, and highlighted the high prevalence of traumatic uveitis in children, which tends to have good visual outcomes. PMID- 26150692 TI - Incidence of retinal detachment associated with atopic dermatitis in Japan: review of cases from 1992 to 2011. AB - PURPOSE: The present study aims to investigate the number and characteristics of retinal detachment with atopic dermatitis (AD) in these 20 years, and the number of the first visit AD outpatients in almost the same period. METHODS: A retrospective review of 101 consecutive surgically treated retinal detachments with AD patients from 1992 to 2011 was conducted. Retinal detachments were divided into two groups: eyes operated on from 1992 to 2001 (former AD group, n=63) and eyes operated on from 2002 to 2011 (recent AD group, n=38). We also reviewed the records of the first visit AD outpatients from 1993 to 2011 except 1998. RESULTS: The percentage of bilateral detachment was significantly higher in the former AD group (14/63) than that in the recent AD group (0/38) (P=0.0002). In addition, patients in the recent AD group were significantly older than those in the former AD group (P=0.0084). The annual cases with non-AD retinal detachment remained invariant for 20 years. The ratio of the retinal detachment with AD for the total retinal detachment was significantly lower in the recent (38/847) AD group than that in the former (63/796) AD group (P=0.0038). The number of the first visit AD outpatients linearly decreased in these 19 years (153 cases in 1993 and 65 cases in 2011). CONCLUSION: Our study indicates an apparent decrease in retinal detachment with AD in the recent 10 years, and might suggest the importance of dermatitis control for prevention of retinal detachment with AD. PMID- 26150693 TI - Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems--enhancement of oral bioavailability. AB - Poor water solubility of a drug is a major challenge in drug delivery research and a main cause for limited bioavailability and pharmacokinetic parameters. This work aims to utilize custom fractional factorial design to assess the development of self-nanoemulsifying drug delivery systems (SNEDDS) and solid nanosuspensions (NS) in order to enhance the oral delivery of atorvastatin (ATR). According to the design, 14 experimental runs of ATR SNEDDS were formulated utilizing the highly ATR solubilizing SNEDDS components: oleic acid, Tween 80, and propylene glycol. In addition, 12 runs of NS were formulated by the antisolvent precipitation-ultrasonication method. Optimized formulations of SNEDDS and solid NS, deduced from the design, were characterized. Optimized SNEDDS formula exhibited mean globule size of 73.5 nm, zeta potential magnitude of -24.1 mV, and 13.5 MUs/cm of electrical conductivity. Optimized solid NS formula exhibited mean particle size of 260.3 nm, 7.4 mV of zeta potential, and 93.2% of yield percentage. Transmission electron microscopy showed SNEDDS droplets formula as discrete spheres. The solid NS morphology showed flaky nanoparticles with irregular shapes using scanning electron microscopy. The release behavior of the optimized SNEDDS formula showed 56.78% of cumulative ATR release after 10 minutes. Solid NS formula showed lower rate of release in the first 30 minutes. Bioavailability estimation in Wistar albino rats revealed an augmentation in ATR bioavailability, relative to ATR suspension and the commercial tablets, from optimized ATR SNEDDS and NS formulations by 193.81% and 155.31%, respectively. The findings of this work showed that the optimized nanocarriers enhance the oral delivery and pharmacokinetic profile of ATR. PMID- 26150694 TI - Disposition and metabolism of [14C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats. AB - Levomilnacipran is approved in the US for the treatment of major depressive disorder in adults. We characterized the metabolic profile of levomilnacipran in humans, monkeys, and rats after oral administration of [(14)C]-levomilnacipran. In vitro binding of levomilnacipran to human plasma proteins was also studied. Unchanged levomilnacipran was the major circulating compound after dosing in all species. Within 12 hours of dosing in humans, levomilnacipran accounted for 52.9% of total plasma radioactivity; the circulating metabolites N-desethyl levomilnacipran N-carbamoyl glucuronide, N-desethyl levomilnacipran, and levomilnacipran N-carbamoyl glucuronide accounted for 11.3%, 7.5%, and 5.6%, respectively. Similar results were seen in monkeys. N-Desethyl levomilnacipran and p-hydroxy levomilnacipran were the main circulating metabolites in rats. Mass balance results indicated that renal excretion was the major route of elimination with 58.4%, 35.5%, and 40.2% of total radioactivity being excreted as unchanged levomilnacipran in humans, monkeys, and rats, respectively. N-Desethyl levomilnacipran was detected in human, monkey, and rat urine (18.2%, 12.4%, and 7.9% of administered dose, respectively). Human and monkey urine contained measurable quantities of levomilnacipran glucuronide (3.8% and 4.1% of administered dose, respectively) and N-desethyl levomilnacipran glucuronide (3.2% and 2.3% of administered dose, respectively); these metabolites were not detected in rat urine. The metabolites p-hydroxy levomilnacipran and p-hydroxy levomilnacipran glucuronide were detected in human urine (<= 1.2% of administered dose), and p-hydroxy levomilnacipran glucuronide was found in rat urine (4% of administered dose). None of the metabolites were pharmacologically active. Levomilnacipran was widely distributed with low plasma protein binding (22%). PMID- 26150696 TI - Design of a gelatin microparticle-containing self-microemulsifying formulation for enhanced oral bioavailability of dutasteride. AB - In this study, a gelatin microparticle-containing self-microemulsifying formulation (SMF) was developed using a spray-drying method to enhance the oral delivery of the poorly water-soluble therapeutic dutasteride. The effect of the amount of gelatin and the type and amount of hydrophilic additives, namely, Gelucire((r)) 44/14, poloxamer 407, sodium lauryl sulfate, Soluplus((r)), SolutolTM HS15, and D-alpha-tocopheryl polyethylene glycol 1000 succinate, on the droplet size, dissolution, and oral absorption of dutasteride from the SMF was investigated. Upon dispersion of the gelatin microparticle-containing SMF in water after spray-drying, the mean droplet size of the aqueous dispersion was in the range of 110-137 nm. The in vitro dissolution and recrystallization results showed that gelatin could be used as a solid carrier and recrystallization inhibitor for the SMF of dutasteride. Furthermore, combination of the gelatin microparticle-containing SMF and Soluplus enhanced the dissolution properties and oral absorption of dutasteride. The results of our study suggest that the gelatin microparticle-containing SMF in combination with Soluplus could be useful to enhance the oral absorption of dutasteride. PMID- 26150695 TI - Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway. AB - Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to investigate the effect of pretreatment with SIM on isoproterenol (ISO)-induced cardiac hypertrophy in rats. Twenty-four male albino Wistar rats weighing 180-200 g were divided into four groups. Groups I and III received normal saline while groups II and IV received SIM (10 mg/kg body weight) for 30 days per gavage. In the last 7 days, rats of groups III and IV were administered ISO (5 mg/kg) intraperitoneally to induce cardiac hypertrophy. Administration of ISO induced an increase in heart-to-body weight (HW/BW) ratio, an increase in serum interleukin-6, and elevated systolic and diastolic blood pressure. Serum levels of lipids, cardiovascular risk indices, and cardiac troponin I and creatine phosphokinase-MB showed significant increase in ISO induced hypertrophic rats. Histopathological examination of heart tissue revealed focal areas of subendocardium degeneration, mononuclear cellular infiltrations, fibrous tissue deposition, and increased thickness of the myocardium of left ventricle. In addition, ISO-administered rats exhibited significant upregulation of cardiac Janus kinase, phosphorylated signal transducer and activator of transcription, and nuclear factor-kappa B. Pretreatment with SIM significantly prevented ISO-induced cardiac hypertrophy, alleviated the altered biochemical parameters, and improved the heart architecture. In conclusion, our study provides evidence that SIM prevented the development of cardiac hypertrophy via modulation of the Janus kinase/signal transducer and activator of transcription signaling pathway in the heart of ISO-administered animals. PMID- 26150697 TI - Sphingosine kinase 1 as an anticancer therapeutic target. AB - The development of chemotherapeutic resistance is a major challenge in oncology. Elevated sphingosine kinase 1 (SK1) levels is predictive of a poor prognosis, and SK1 overexpression may confer resistance to chemotherapeutics. The SK/sphingosine 1-phosphate (S1P)/sphingosine-1-phosphate receptor (S1PR) signaling pathway has been implicated in the progression of various cancers and in chemotherapeutic drug resistance. Therefore, SK1 may represent an important target for cancer therapy. Targeting the SK/S1P/S1PR signaling pathway may be an effective anticancer therapeutic strategy, particularly in the context of overcoming drug resistance. This review summarizes our current understanding of the role of SK/S1P/S1PR signaling in cancer and development of SK1 inhibitors. PMID- 26150698 TI - Development of biosimilars in an era of oncologic drug shortages. AB - Acute and chronic shortages of various pharmaceuticals and particularly of sterile injectable products are being reported on a global scale, prompting evaluation of more effective strategies to manage current shortages and development of new, high-quality pharmaceutical products to mitigate the risk of potential future shortages. Oncology drugs such as liposomal doxorubicin and 5 fluorouracil represent examples of first-choice drugs critically affected by shortages. Survey results indicate that the majority of hospitals and practicing oncologists have experienced drug shortages, which may have compromised patient safety and clinical outcomes, and increased health care costs, due to delays or changes in treatment regimens. Clinical trials evaluating novel agents in combination with standard-of-care drugs are also being affected by drug shortages. Clinical and ethical considerations on treatment objectives, drug indication, and availability of alternative options may help in prioritizing cancer patients involved in active drug shortages. The United States Food and Drug Administration and the European Medicines Agency have identified manufacturing problems, delays in supply, and lack of available active ingredients as the most frequent causes of recent or ongoing drug shortages, and have released specific guidance to monitor, manage, and reduce the risk of shortages. The upcoming loss of exclusivity for a number of anticancer biologics, together with the introduction of an abbreviated approval pathway for biosimilars, raises the question of whether these products will be vulnerable to shortages. Future supply by reliable manufacturers of well characterized biosimilar monoclonal antibodies, developed in compliance with regulatory and manufacturing guidelines and with substantial investments, may contribute to prevent future biologics shortages and ensure access to effective and safe treatment options for patients with cancer. Preclinical and clinical characterization is ongoing for potential biosimilars of trastuzumab, rituximab, and bevacizumab, with promising results. PMID- 26150699 TI - Improving dissolution and oral bioavailability of pranlukast hemihydrate by particle surface modification with surfactants and homogenization. AB - The present study was carried out to develop an oral formulation of pranlukast hemihydrate with improved dissolution and oral bioavailability using a surface modified microparticle. Based on solubility measurements, surface-modified pranlukast hemihydrate microparticles were manufactured using the spray-drying method with hydroxypropylmethyl cellulose, sucrose laurate, and water and without the use of an organic solvent. The hydrophilicity of the surface-modified pranlukast hemihydrate microparticle increased, leading to enhanced dissolution and oral bioavailability of pranlukast hemihydrate without a change in crystallinity. The surface-modified microparticles with an hydroxypropylmethyl cellulose/sucrose laurate ratio of 1:2 showed rapid dissolution of up to 85% within 30 minutes in dissolution medium (pH 6.8) and oral bioavailability higher than that of the commercial product, with approximately 2.5-fold and 3.9-fold increases in area under the curve (AUC 0 -> 12 h) and peak plasma concentration, respectively. Therefore, the surface-modified microparticle is an effective oral drug delivery system for the poorly water-soluble therapeutic pranlukast hemihydrate. PMID- 26150700 TI - A meta-analysis for CXCR4 as a prognostic marker and potential drug target in non small cell lung cancer. AB - BACKGROUND: Recent reports have shown that C-X-C chemokine receptor type 4 (CXCR4) is a candidate oncogene in several types of human tumors, including non small cell lung cancer (NSCLC). However, the correlation between CXCR4 expression and clinicopathological characteristics of NSCLC remains controversial and has not been emphasized. The aim of this study is to quantitatively evaluate the association of CXCR4 expression with the incidence of NSCLC and clinicopathological characteristics by performing a meta-analysis. METHODS: A detailed literature search was carried out for related research publications. Only articles in which CXCR4 expression was detected by immunohistochemical staining were included. Odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were calculated and summarized. RESULTS: Final analysis of 1,872 NSCLC patients from 19 eligible studies was performed. We observed that CXCR4 expression was significantly higher in NSCLC than in normal lung tissue, based on the pooled OR from ten studies, including 678 NSCLCs and 189 normal lung tissues (OR =16.66, 95% CI =6.94-40.02, P<0.00001). CXCR4 expression was also significantly associated with clinical stages, metastatic status, and overall survival (OS) in NSCLC patients. In addition, CXCR4 mRNA high expression was found to correlate with worse OS of all NSCLC patients followed for 20 years, HR =1.24, P=0.0047. CONCLUSION: The present meta-analysis indicated that CXCR4 protein expression is associated with an increased risk and worse survival in NSCLC patients. The aberrant CXCR4 protein and mRNA expression play an important role in the carcinogenesis and metastasis of NSCLC. PMID- 26150701 TI - Effect of renal impairment on the pharmacokinetics of levomilnacipran following a single oral dose of levomilnacipran extended-release capsule in humans. AB - PURPOSE: Levomilnacipran extended-release (ER) is indicated for treatment of major depressive disorder in adults. We evaluated the pharmacokinetic and safety profile of levomilnacipran ER in individuals with impaired renal function. METHODS: A total of 32 individuals participated in four groups (eight in each group) with normal, mild, moderately, or severely impaired renal function. Each participant received one dose of levomilnacipran ER 40 mg. Blood and urine were assayed using liquid chromatography/tandem mass spectrometry. Results between normal and renally impaired groups were compared using analysis of variance. Safety measures included adverse events, laboratory evaluations, vital signs, suicidality, and electrocardiograms. RESULTS: Following administration of levomilnacipran, mean (standard deviation) maximum plasma concentration in participants with normal renal function, and mild, moderate, or severe renal impairment was 83.9 (21.0), 81.8 (23.4), 98.7 (18.1), and 122.1 (35.1) (ng/mL), respectively; area under the curve from time zero to infinity was 2,101.0 (516.9), 2,587.8 (649.9), 4,016.4 (995.4), and 5,900.8 (1,799.3) (h . ng/mL), respectively; terminal elimination half-life was 13.5 (2.8), 17.3 (3.5), 19.1 (4.6), and 27.7 (7.4) (hours), respectively; and renal clearance was 175.9 mL/min, 114.7 mL/min, 69.9 mL/min, and 28.6 mL/min, respectively. Levomilnacipran ER was generally well tolerated with no safety issues of concern identified. CONCLUSION: Renal impairment was associated with increased plasma levels of levomilnacipran and prolonged half-life. No dose adjustment is required for individuals with mild renal impairment; the recommended maximum daily maintenance dose of levomilnacipran ER should not exceed 80 mg for individuals with moderate renal impairment and 40 mg for individuals with severe renal impairment. PMID- 26150702 TI - Reasons for not initiating osteoporosis therapy among a managed care population. AB - BACKGROUND: Many women with osteoporosis do not initiate osteoporosis treatment. OBJECTIVE: To examine patients' reasons for not initiating osteoporosis treatment among women with osteoporosis. METHODS: Survey recipients were identified from a national US claims database and included women >=55 years with an osteoporosis diagnosis from January 1, 2010 to March 31, 2012 as defined by: 1) osteoporosis diagnosis coupled with bone mineral density test within 183 days of diagnosis and/or 2) osteoporosis-related fracture. Eligibility required no claims for osteoporosis medication 1) at least 12 months and up to 5 years prior to osteoporosis diagnosis and 2) at least 6 months after osteoporosis diagnosis. Continuous enrollment for 18 months (6 months pre-osteoporosis and 12 months post osteoporosis diagnosis) was also required. A total of 2,000 patients with the most recent osteoporosis diagnosis were mailed a survey. Respondents reporting that they did not initiate physician-recommended osteoporosis medication, after either their physician told them they had osteoporosis or they experienced a fracture since age 45 years, were asked for reasons why they did not initiate treatment. RESULTS: There were 430 patients who returned a complete survey; mean age was 61% and 21.6% had a fracture. A total of 197 (45.8%) patients reported their physician diagnosed osteoporosis and 117 (59.3%) of those were recommended osteoporosis medication; 44 of the 117 patients (37.6%) did not initiate recommended osteoporosis medication by the time of survey. The primary reasons for not initiating osteoporosis medication were concern over side effects (77.3%), medication costs (34.1%), and pre-existing gastrointestinal concerns (25.0%). CONCLUSION: Among respondents, 41% of patients whose physician diagnosed osteoporosis were not recommended osteoporosis treatment and 38% of patients who were recommended osteoporosis treatment did not initiate treatment within approximately 2 years of diagnosis. Concerns with side effects of osteoporosis treatment, medication costs, and pre-existing gastrointestinal concerns were the most common reasons for not initiating recommended treatment. PMID- 26150703 TI - Measuring the quality of patient-centered care: why patient-reported measures are critical to reliable assessment. AB - PURPOSE: The Institute of Medicine (IOM) identified patient-centeredness as crucial to quality health care. The IOM endorsed six patient-centeredness dimensions that stipulated that care must be: respectful to patients' values, preferences, and expressed needs; coordinated and integrated; provide information, communication, and education; ensure physical comfort; provide emotional support; and involve family and friends. Patient-reported measures examine the patient's perspective and are essential to the accurate assessment of patient-centered care. This article's objectives are to: 1) use the six IOM endorsed patient-centeredness dimensions as a framework to outline why patient reported measures are crucial to the reliable measurement of patient-centered care; and 2) to identify existing patient-reported measures that assess each patient-centered care dimension. METHODS: For each IOM-endorsed patient centeredness dimension, the published literature was searched to highlight the essential role of patients in assessing patient-centered care and informing quality improvement efforts. Existing literature was also searched to identify examples of patient-reported measures that assess each patient-centeredness dimension. CONCLUSION: Patient-reported measures are arguably the best way to measure patient-centeredness. For instance, patients are best positioned to determine whether care aligns with patient values, preferences, and needs and the Measure of Patient Preferences is an example of a patient-reported measure that does so. Furthermore, only the patient knows whether they received the level of information desired, and if information was understood and can be recalled. Patient-reported measures that examine information provision include the Lung Information Needs Questionnaire and the EORTC QLQ-INFO25. In relation to physical comfort, only patients can report the severity of physical symptoms and whether medications provide adequate relief. Patient-reported measures that investigate physical comfort include the Pain Care Quality Survey and the Brief Pain Inventory. Using patient-reported measures to regularly measure patient-centered care is critical to identifying areas of health care where improvements are needed. PMID- 26150704 TI - Randomized comparative study of left versus right radial approach in the setting of primary percutaneous coronary intervention for ST-elevation myocardial infarction. AB - BACKGROUND: Growing evidence suggests that the left radial approach (LRA) is related to decreased coronary procedure duration and fewer cerebrovascular complications as compared to the right radial approach (RRA) in elective percutaneous coronary intervention (PCI). However, the feasibility of LRA in primary PCI has yet to be studied further. Therefore, the aim of this study was to investigate the efficacy of LRA compared with RRA for primary PCI in ST elevation myocardial infarction (STEMI) patients. MATERIALS AND METHODS: A total of 200 consecutive patients with STEMI who received primary PCI were randomized to LRA (number [n]=100) or RRA (n=100). The study endpoint was needle-to-balloon time, defined as the time from local anesthesia infiltration to the first balloon inflation. Radiation dose by measuring cumulative air kerma (CAK) and CAK dose area product, as well as fluoroscopy time and contrast volume were also investigated. RESULTS: There were no significant differences in the baseline characteristics between the two groups. The coronary procedural success rate was similar between both radial approaches (98% for left versus 94% for right; P=0.28). Compared with RRA, LRA had significantly shorter needle-to-balloon time (16.0+/-4.8 minutes versus 18.0+/-6.5 minutes, respectively; P=0.02). Additionally, fluoroscopy time (7.4+/-3.4 minutes versus 8.8+/-3.5 minutes, respectively; P=0.01) and CAK dose area product (51.9+/-30.4 Gy cm(2) versus 65.3+/-49.1 Gy cm(2), respectively; P=0.04) were significantly lower with LRA than with RRA. CONCLUSION: Primary PCI can be performed via LRA with earlier blood flow restoration in the infarct-related artery and lower radiation exposure when compared with RRA; therefore, the LRA may become a feasible and attractive alternative to perform primary PCI for STEMI patients. PMID- 26150705 TI - Outcomes of vaginal hysterectomy and constricting colporrhaphy with concurrent levator myorrhaphy and high perineorrhaphy in women older than 75 years of age. AB - OBJECTIVES: We performed constricting anterior and posterior colporrhaphy, levator myorrhaphy, and high perineorrhaphy with concurrent hysterectomy, and investigated the intraoperative complications, and short-term outcomes of these constricting procedures in patients aged 75 years or older. METHODS: We searched our hospital database for cases, between January 2011 and January 2014, of women aged over 75 years who underwent surgery for pelvic organ prolapse of stage 2 or higher, via vaginal hysterectomy, constricting anterior and posterior colporrhaphy, levator myorrhaphy, and high perineorrhaphy, with or without treatment of urinary incontinence. All volunteers were evaluated via pelvic examination using the pelvic organ prolapse quantification system, the modified Decision Regret Scale-Pelvic Floor Disorders form, the Satisfaction Decision Scale-Pelvic Floor Disorders form, and the Pelvic Floor Distress Inventory form. RESULTS: Fifty-four patients were included in the study. The mean follow-up time was 24.4 months after constricting surgery (range: 8-44 months). There were four cases (7%) of de novo urge incontinence (the symptoms resolved upon prescription of anticholinergic medication). Two patients developed de novo stress urinary incontinence after the procedure and were treated via transobturator sling surgery using Safyre T((r)) polypropylene monofilament slings. No anatomical or subjective recurrence of prolapse was noted during the follow-up period. No patient required additional surgery for recurrence of prolapse. CONCLUSION: Constricting anterior and posterior colporrhaphy, levator myorrhaphy, and high perineorrhaphy with concurrent hysterectomy is a feasible, safe, and effective surgical option in elderly patients at low anesthesiological risk. The decision to perform an incontinence procedure should be individualized based on preoperative findings after prolapse reduction. PMID- 26150707 TI - Fracture prevention service to bridge the osteoporosis care gap. AB - BACKGROUND: A care gap exists between the health care needs of older persons with fragility fractures and the therapeutic answers they receive. The Fracture Prevention Service (FPS), a tailored in-hospital model of care, may effectively bridge the osteoporosis care gap for hip-fractured older persons. The purpose of this study was to evaluate the efficacy of the FPS in targeting persons at high risk of future fracture and to improve their adherence to treatment. METHODS: This was a prospective observational study conducted in a teaching hospital with traumatology and geriatric units, and had a pre-intervention and post intervention phase. The records of 172 participants were evaluated in the pre intervention phase, while data from 210 participants were gathered in the post intervention phase. All participants underwent telephone follow-up at 12 months after hospital discharge. The participants were patients aged >=65 years admitted to the orthopedic acute ward who underwent surgical repair of a proximal femoral fracture. A multidisciplinary integrated model of care was established. Dedicated pathways were implemented in clinical practice to optimize the identification of high-risk persons, improve their evaluation through bone mineral density testing and blood examinations, and initiate an appropriate treatment for secondary prevention of falls and fragility fractures. RESULTS: Compared with the pre intervention phase, more hip-fractured persons received bone mineral density testing (47.62% versus 14.53%, P<0.0001), specific pharmacological treatments (48.51% versus 17.16%, P<0.0001), and an appointment for evaluation at a fall and fracture clinic (52.48% versus 2.37%, P<0.0001) in the post-intervention phase. Independent of some confounders, implementation of the FPS was positively associated with recommendations for secondary fracture prevention at discharge (P<0.0001) and with 1-year adherence to pharmacological treatment (P<0.0001). CONCLUSION: The FPS is an effective multidisciplinary integrated model of care to optimize identification of older persons at highest risk for fragility fracture, to improve their clinical management, and to increase adherence to prescriptions. PMID- 26150708 TI - Geriatrician interventions on medication prescribing for frail older people in residential aged care facilities. AB - OBJECTIVE: In Australian residential aged care facilities (RACFs), the use of certain classes of high-risk medication such as antipsychotics, potent analgesics, and sedatives is high. Here, we examined the prescribed medications and subsequent changes recommended by geriatricians during comprehensive geriatric consultations provided to residents of RACFs via videoconference. DESIGN: This is a prospective observational study. SETTING: Four RACFs in Queensland, Australia, are included. PARTICIPANTS: A total of 153 residents referred by general practitioners for comprehensive assessment by geriatricians delivered by video-consultation. RESULTS: Residents' mean (standard deviation, SD) age was 83.0 (8.1) years and 64.1% were female. They had multiple comorbidities (mean 6), high levels of dependency, and were prescribed a mean (SD) of 9.6 (4.2) regular medications. Ninety-one percent of patients were taking five or more medications daily. Of total medications prescribed (n=1,469), geriatricians recommended withdrawal of 9.8% (n=145) and dose alteration of 3.5% (n=51). New medications were initiated in 47.7% (n=73) patients. Of the 10.3% (n=151) medications considered as high risk, 17.2% were stopped and dose altered in 2.6%. CONCLUSION: There was a moderate prevalence of potentially inappropriate high-risk medications. However, geriatricians made relatively few changes, suggesting either that, on balance, prescription of these medications was appropriate or, because of other factors, there was a reluctance to adjust medications. A structured medication review using an algorithm for withdrawing medications of high disutility might help optimize medications in frail patients. Further research, including a broader survey, is required to understand these dynamics. PMID- 26150706 TI - Epidemiology and management of osteoporosis in the People's Republic of China: current perspectives. AB - With the progressive aging of the population, osteoporosis has gradually grown into a global health problem for men and women aged 50 years and older because of its consequences in terms of disabilities and fragility fractures. This is especially true in the People's Republic of China, which has the largest population and an increasing proportion of elderly people, as osteoporosis has become a serious challenge to the Chinese government, society, and family. Apart from the fact that all osteoporotic fractures can increase the patient's morbidity, they can also result in fractures of the hip and vertebrae, which are associated with a significantly higher mortality. The cost of osteoporotic fractures, moreover, is a heavy burden on families, society, and even the country, which is likely to increase in the future due, in part, to the improvement in average life expectancy. Therefore, understanding the epidemiology of osteoporosis is essential and is significant for developing strategies to help reduce this problem. In this review, we will summarize the epidemiology of osteoporosis in the People's Republic of China, including the epidemiology of osteoporotic fractures, focusing on preventive methods and the management of osteoporosis, which consist of basic measures and pharmacological treatments. PMID- 26150709 TI - Impact of direct substitution of arm span length for current standing height in elderly COPD. AB - BACKGROUND: Arm span length is related to standing height and has been studied as a substitute for current standing height for predicting lung function parameters. However, it has never been studied in elderly COPD patients. PURPOSE: To evaluate the accuracy of substituting arm span length for current standing height in the evaluation of pulmonary function parameters and severity classification in elderly Thai COPD patients. MATERIALS AND METHODS: Current standing height and arm span length were measured in COPD patients aged >60 years. Postbronchodilator spirometric parameters, forced vital capacity (FVC), forced expiratory volume in first second (FEV1), and ratio of FEV1/FVC (FEV1%), were used to classify disease severity according to global initiative for chronic obstructive lung disease criteria. Predicted values for each parameter were also calculated separately utilizing current standing height or arm span length measurements. Student's t tests and chi-squared tests were used to compare differences between the groups. Statistical significance was set at P<0.05. RESULTS: A total of 106 COPD patients with a mean age of 72.1+/-7.8 years, mean body mass index of 20.6+/-3.8 kg/m(2), and mean standing height of 156.4+/-8.3 cm were enrolled. The mean arm span length exceeded mean standing height by 7.7+/-4.6 cm (164.0+/-9.0 vs 156.4+/-8.3 cm, P<0.001), at a ratio of 1.05+/-0.03. Percentages of both predicted FVC and FEV1 values based on arm span length were significantly lower than those using current standing height (76.6+/-25.4 vs 61.6+/-16.8, P<0.001 and 50.8+/-25.4 vs 41.1+/-15.3, P<0.001). Disease severity increased in 39.6% (42/106) of subjects using arm span length over current standing height for predicted lung function. CONCLUSION: Direct substitution of arm span length for current standing height in elderly Thai COPD patients should not be recommended in cases where arm span length exceeds standing height by more than 4 cm. PMID- 26150710 TI - Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: We investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD). METHODS: We studied 100 (20 female; mean age: 68+/-10 years) patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred +/-21%; FEV1/forced vital capacity [FVC]: 53%+/-10%) by impulse oscillometry system. Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa.s.L(-1)) and the fall in resistance from 5 Hz to 20 Hz (R5 - R20) were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa.s.L(-1)) was also measured. Significant response to bronchodilator (salbutamol 400 MUg) was expressed as absolute (>=0.2 L) and percentage (>=12%) change relative to the prebronchodilator value of FEV1 (flow responders, FRs) and FVC (volume responders, VRs). RESULTS: Eighty out of 100 participants had R5 - R20 >0.03 kPa.s.L(-1) (> upper normal limit) and, compared to patients with R5 - R20 <=0.030 kPa.s.L(-1), showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons). Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 - R20 values (P<0.05), lower X5 values (P<0.05), and greater airflow obstruction and lung hyperinflation. CONCLUSION: This study shows that peripheral airway resistance is increased in the vast majority of patients with COPD, who showed worse respiratory reactance, worse spirometry results, more severe lung hyperinflation, and poorer health status. Small airway dysfunction was also associated with the bronchodilator responsiveness in terms of FVC, but not in terms of FEV1. PMID- 26150711 TI - Influence of pulmonary emphysema on COPD assessment test-oriented categorization in GOLD document. AB - BACKGROUND: The COPD assessment test (CAT) score is a key component of the multifactorial assessment of COPD in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines of 2014. Nevertheless, little is known regarding the differences among COPD categories in terms of clinical parameters such as pulmonary function or radiological findings. Thus, our aims in this study were to evaluate the associations between CAT scores and pulmonary clinical parameters, and to investigate factors that could discriminate between a "less symptomatic group" (categories A and C) and a "more symptomatic group" (categories B and D) among stable COPD patients. METHODS: We enrolled 200 outpatients at Chiba University Hospital. Study subjects were assessed by CAT, pulmonary function testing, and multidetector computed tomography (MDCT). We assessed possible correlations between these indices. RESULTS: CAT scores were negatively correlated with percentage of the forced expiratory volume in 1 second predicted value (FEV1 %predicted) and percentage of the diffusing capacity for carbon monoxide per liter of lung volume predicted value (DLCO/VA [%predicted]) results and positively correlated with low attenuation volume percentage (LAV%) and residual volume to total lung capacity ratios (RV/TLC). In the "more symptomatic group" (category B or D), the mean DLCO/VA (%predicted) was significantly lower and the mean LAV% and RV/TLC was significantly higher than those in the "less symptomatic group" (category A or C), respectively. Interestingly, those in category B had higher mean LAV% compared to those in category C. CONCLUSION: CAT scores were significantly correlated with pulmonary function parameters and emphysematous changes on MDCT. The new GOLD classification system would be a step toward a phenotypic approach, especially taking into account the degree of emphysema and hyperinflation. PMID- 26150712 TI - Relationship between nutritional risk and exercise capacity in severe chronic obstructive pulmonary disease in male patients. AB - OBJECTIVE: The nutritional status of chronic obstructive pulmonary disease (COPD) patients is associated with their exercise capacity. In the present study, we have explored the relationship between nutritional risk and exercise capacity in severe male COPD patients. METHODS: A total of 58 severe COPD male patients were enrolled in this study. The patients were assigned to no nutritional risk group (n=33) and nutritional risk group (n=25) according to the Nutritional Risk Screening (NRS, 2002) criteria. Blood gas analysis, conventional pulmonary function testing, and cardiopulmonary exercise testing were performed on all the patients. RESULTS: Results showed that the weight and BMI of the patients in the nutritional risk group were significantly lower than in the no nutritional risk group (P<0.05). The pulmonary diffusing capacity for carbon monoxide of the no nutritional risk group was significantly higher than that of the nutritional risk group (P<0.05). Besides, the peak VO2 (peak oxygen uptake), peak O2 pulse (peak oxygen pulse), and peak load of the nutritional risk group were significantly lower than those of the no nutritional risk group (P<0.05) and there were significantly negative correlations between the NRS score and peak VO2, peak O2 pulse, or peak load (r<0, P<0.05). CONCLUSION: The association between exercise capacity and nutritional risk based on NRS 2002 in severe COPD male patients is supported by these results of this study. PMID- 26150713 TI - Peak expiratory flow rate as a surrogate for forced expiratory volume in 1 second in COPD severity classification in Thailand. AB - BACKGROUND: There are limited studies directly comparing correlation and agreement between peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1) for severity classification of COPD. However, clarifying the role of PEFR as a surrogate of COPD severity classification instead of FEV1 is essential in situations and areas where spirometry is not routinely available. PURPOSE: To evaluate the agreement between FEV1 and PEFR using Global initiative for chronic Obstructive Lung Disease (GOLD) severity classification criteria. MATERIALS AND METHODS: This cross-sectional study included stable COPD patients. Both absolute values and % predicted FEV1 and % predicted PEFR were obtained from the same patients at a single visit. The severity of COPD was classified according to GOLD criteria. Pearson's correlation coefficient was used to examine the relationship between FEV1 and PEFR. The agreement of % predicted FEV1 and % predicted PEFR in assigning severity categories was calculated using Kappa statistic, and identification of the limits of agreement was by Bland-Altman analysis. Statistical significance was set at P-value <0.05. RESULTS: Three hundred stable COPD patients were enrolled; 195 (65.0%) male, mean age 70.4+/-9.4 years, and mean % predicted FEV1 51.4+/-20.1. Both correlations between the % predicted FEV1 and PEFR as well as the absolute values were strongly significant (r=0.76, P<0.001 and r=0.87, P<0.001, respectively). However, severity categories of airflow limitation based on % predicted FEV1 or PEFR intervals were concordant in only 179 patients (59.7%). The Kappa statistic for agreement was 0.41 (95% confidence interval, 0.34-0.48), suggesting unsatisfied agreement. The calculated limits of agreement were wide (+27.1% to -28.9%). CONCLUSION: Although the correlation between FEV1 and PEFR measurements were strongly significant, the agreement between the two tests was unsatisfied and may influence inappropriate clinical decision making in diagnosis, severity classification, and management of COPD. PMID- 26150714 TI - Influence of nanotopography on periodontal ligament stem cell functions and cell sheet based periodontal regeneration. AB - Periodontal regeneration is an important part of regenerative medicine, with great clinical significance; however, the effects of nanotopography on the functions of periodontal ligament (PDL) stem cells (PDLSCs) and on PDLSC sheet based periodontal regeneration have never been explored. Titania nanotubes (NTs) layered on titanium (Ti) provide a good platform to study this. In the current study, the influence of NTs of different tube size on the functions of PDLSCs was observed. Afterward, an ectopic implantation model using a Ti/cell sheets/hydroxyapatite (HA) complex was applied to study the effect of the NTs on cell sheet based periodontal regeneration. The NTs were able to enhance the initial PDLSC adhesion and spread, as well as collagen secretion. With the Ti/cell sheets/HA complex model, it was demonstrated that the PDLSC sheets were capable of regenerating the PDL tissue, when combined with bone marrow mesenchymal stem cell (BMSC) sheets and HA, without the need for extra soluble chemical cues. Simultaneously, the NTs improved the periodontal regeneration result of the ectopically implanted Ti/cell sheets/HA complex, giving rise to functionally aligned collagen fiber bundles. Specifically, much denser collagen fibers, with abundant blood vessels as well as cementum-like tissue on the Ti surface, which well-resembled the structure of natural PDL, were observed in the NT5 and NT10 sample groups. Our study provides the first evidence that the nanotopographical cues obviously influence the functions of PDLSCs and improve the PDLSC sheet based periodontal regeneration size dependently, which provides new insight to the periodontal regeneration. The Ti/cell sheets/HA complex may constitute a good model to predict the effect of biomaterials on periodontal regeneration. PMID- 26150715 TI - The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment. AB - The therapeutic effect of methotrexate (MTX)-conjugated Pluronic-based polymeric mixed micelles (F127/P105-MTX) on the folate receptor-overexpressing tumors treatment was investigated in this study. Due to its high structural similarity to folic acid and the high expression of folate receptor in most solid tumors, MTX serves as not only a cytotoxic agent but also a homing ligand. Cellular uptake and the endocytic mechanism studies of MTX-conjugated mixed micelles were performed in folate receptor-rich KBv and folate receptor-deficient A-549 cancer cells. Additionally, the efficacy and safety studies of F127/P105-MTX in KBv tumor-bearing mice were evaluated. Results indicate that F127/P105-MTX significantly enhanced the cellular uptake in KBv cells as compared to that of conventional non-MTX-conjugated mixed micelles. Moreover, the results showed that F127/P105-MTX can be internalized by both caveolae- and clathrin-mediated endocytosis in energy-dependent and folate receptor-dependent manners. The in vitro and in vivo antitumor efficacies of F127/P105-MTX were significantly enhanced in comparison with MTX-entrapped mixed micelles. Furthermore, no acute toxicities to hematological system and major organs have been observed after intravenous administration during the regimen. Therefore, our results suggest that F127/P105-MTX could be an effective and safe nano-drug delivery system for cancer therapy, especially for the folate receptor-rich cancer treatment. PMID- 26150716 TI - Optimized zein nanospheres for improved oral bioavailability of atorvastatin. AB - BACKGROUND: This work focuses on the development of atorvastatin utilizing zein, a natural, safe, and biocompatible polymer, as a nanosized formulation in order to overcome the poor oral bioavailability (12%) of the drug. METHODS: Twelve experimental runs of atorvastatin-zein nanosphere formula were formulated by a liquid-liquid phase separation method according to custom fractional factorial design to optimize the formulation variables. The factors studied were: weight % of zein to atorvastatin (X1), pH (X2), and stirring time (X3). Levels for each formulation variable were designed. The selected dependent variables were: mean particle size (Y1), zeta potential (Y2), drug loading efficiency (Y3), drug encapsulation efficiency (Y4), and yield (Y5). The optimized formulation was assayed for compatibility using an X-ray diffraction assay. In vitro diffusion of the optimized formulation was carried out. A pharmacokinetic study was also done to compare the plasma profile of the atorvastatin-zein nanosphere formulation versus atorvastatin oral suspension and the commercially available tablet. RESULTS: The optimized atorvastatin-zein formulation had a mean particle size of 183 nm, a loading efficiency of 14.86%, and an encapsulation efficiency of 29.71%. The in vitro dissolution assay displayed an initial burst effect, with a cumulative amount of atorvastatin released of 41.76% and 82.3% after 12 and 48 hours, respectively. In Wistar albino rats, the bioavailability of atorvastatin from the optimized atorvastatin-zein formulation was 3-fold greater than that from the atorvastatin suspension and the commercially available tablet. CONCLUSION: The atorvastatin-zein nanosphere formulation improved the oral delivery and pharmacokinetic profile of atorvastatin by enhancing its oral bioavailability. PMID- 26150717 TI - Enzyme-responsive nanocomposites for wound infection prophylaxis in burn management: in vitro evaluation of their compatibility with healing processes. AB - Responsive, theranostic nanosystems, capable of both signaling and treating wound infections, is a sophisticated approach to reduce the most common and potentially traumatizing side effects of burn wound treatment: slowed wound healing due to prophylactic anti-infective drug exposure as well as frequent painful dressing changes. Antimicrobials as well as dye molecules have been incorporated into biodegradable nanosystems that release their content only in the presence of pathogens. Following nanocarrier degradation by bacterial enzymes, any infection will thus emit a visible signal and be effectively treated at its source. In this study, we investigated the effect of fluorescent-labeled hyaluronan nanocapsules containing polyhexanide biguanide and poly-L-lactic acid nanoparticles loaded with octenidine on primary human dermal microvascular endothelial cells, which play a major role in cutaneous wound healing. Microscopic and flow cytometric analysis indicated a time-dependent uptake of both the nanocapsules and the nanoparticles. However, enzyme immunoassays showed no significant influence on the expression of pro-inflammatory cell adhesion molecules and cytokines by the endothelial cells. Under angiogenic-stimulating conditions, the potential to form capillary-like structures in co-culture with dermal fibroblasts was not inhibited. Furthermore, cytotoxicity studies (the MTS and crystal violet assay) after short- and long-term exposure to the materials demonstrated that both systems exhibited less toxicity than solutions of the antiseptic agents alone in comparable concentrations. The results indicate that responsive antimicrobial nanocomposites could be used as an advanced drug delivery system and a promising addition to current best practice wound infection prophylaxis with few side effects. PMID- 26150718 TI - Degradability, bioactivity, and osteogenesis of biocomposite scaffolds of lithium containing mesoporous bioglass and mPEG-PLGA-b-PLL copolymer. AB - Biocomposite scaffolds of lithium (Li)-containing mesoporous bioglass and monomethoxy poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine) (mPEG-PLGA-b-PLL) copolymer were fabricated in this study. The results showed that the water absorption and degradability of Li-containing mesoporous bioglass/mPEG-PLGA-b-PLL composite (l-MBPC) scaffolds were obviously higher than Li-containing bioglass/mPEG-PLGA-b-PLL composite (l-BPC) scaffolds. Moreover, the apatite-formation ability of l-MBPC scaffolds was markedly enhanced as compared with l-BPC scaffolds, indicating that l-MBPC scaffolds containing mesoporous bioglass exhibited good bioactivity. The cell experimental results showed that cell attachment, proliferation, and alkaline phosphatase activity of MC3T3-E1 cells on l-MBPC scaffolds were remarkably improved as compared to l-BPC scaffolds. In animal experiments, the histological elevation results revealed that l-MBPC scaffolds significantly promoted new bone formation, indicating good osteogenesis. l-MBPC scaffolds with improved properties would be an excellent candidate for bone tissue repair. PMID- 26150719 TI - Efficacy and safety of flexibly dosed paliperidone palmitate in Chinese patients with acute schizophrenia: an open-label, single-arm, prospective, interventional study. AB - This open-label, single-arm, multicenter, 13-week, prospective study explored the efficacy, safety, and tolerability of paliperidone palmitate (150 milligram equivalents [mg eq] [day 1], 100 mg eq [day 8], both deltoid injections; 75-150 mg eq, deltoid/gluteal injection) in Chinese patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score >=70), who previously had unsatisfactory therapeutic effect following oral antipsychotic treatment (without washout period). Primary efficacy endpoint was percentage of patients with >=30% improvement in the PANSS total score at the end of 13 weeks. Secondary efficacy endpoints included change from baseline to end of week 13 in PANSS total score, PANSS subscale scores, Marder factor scores, Clinical Global Impressions Severity score, and Personal and Social Performance Scale scores. Overall, 477/610 enrolled patients (full analysis set, 78.2%) completed the study (men: 55.1%; women: 44.9%; mean age: 31.5 years). Total, 443/610 (72.6%, full analysis set) patients achieved primary endpoint (mean [standard deviation] change from baseline: -30.9 [19.51]). All secondary endpoints demonstrated significant improvement at the end of 13 weeks. One death occurred during this acute phase. The most common (>5%) treatment-emergent adverse events were extrapyramidal disorders (8.4%). The efficacy and safety data are consistent with other short term, placebo-controlled studies of paliperidone palmitate conducted in similar populations. PMID- 26150721 TI - Validity and reliability of the Turkish version of CRAFFT Substance Abuse Screening Test among adolescents. AB - AIM: This study aimed to validate the CRAFFT diagnostic test, against the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition, Axis 1 based diagnostic inventory in a Turkish population of adolescents. METHOD: The 124 adolescents who were 15-18 years old were enrolled to this study. CRAFFT was self-administered. Interviews took approximately 30 minutes, including the DSM-IV diagnostic interview for alcohol/drug dependence. RESULTS: The mean age of subjects was 16.653 years (minimum: 15 years, maximum: 18 years). A score of 2 or higher in part B was found to be optimal for detecting youths with substance dependence problems (sensitivity: 0.82; specificity: 0.88) and it was sufficiently discriminative. CONCLUSION: The CRAFFT is a valid and reliable instrument for identifying Turkish-speaking youths at risk for substance use disorders. PMID- 26150720 TI - Telomere length in blood cells is related to the chronicity, severity, and recurrence rate of schizophrenia. AB - INTRODUCTION: Telomere shortening is strongly associated with higher mortality rates and has been shown in a number of age-related diseases, such as cardiovascular disorders, diabetes mellitus, Alzheimer's disease, and psychiatric disorders. Oxidative stress is known to induce DNA breaks and genome instability. Telomeric DNA rich in guanosine is particularly sensitive to such oxidative damages. Psychosis is associated with a disequilibrium between free radical production and antioxidative defense. Although telomere attrition has been demonstrated in schizophrenia, no relationship has been reported between telomere length and severity of schizophrenia. AIM: The aim of the present study was to identify differences in telomere length in peripheral blood cells between patients with chronic schizophrenia (C-SCZ) and early schizophrenia (E-SCZ) and to identify any relationship between telomere length and disease chronicity and severity. METHODS: Relative average telomere lengths were determined using qPCR assay in patients with E-SCZ (n=42) and C-SCZ (n=44) hospitalized due to schizophrenia exacerbation. E-SCZ was diagnosed when less than 2 years had passed since the beginning of psychotic symptoms. The severity of symptoms was assessed using appropriate scales. RESULTS: The severity of schizophrenia symptoms, as well as the number of psychotic episodes and hospital admissions, correlated significantly with telomere length in univariate analyses. Regression analysis revealed that a model incorporating study group (E-SCZ or C-ECZ), sex, and age, as well as the combined number of documented psychotic episodes and hospital admissions, can significantly predict the length of telomeres in patients with schizophrenia, with over 50% of variance in telomere length explained by the model (adjusted R (2)=0.512). CONCLUSION: The results of the current study indicate that the recurrence of psychotic symptoms as well as their intensity and chronicity may be correlated with telomere attrition, which is well known to contribute to the development of premature senescence and age-related diseases. PMID- 26150722 TI - The social functional outcome of being naturalistically treated with paliperidone extended-release in patients with schizophrenia. AB - BACKGROUND: Social functioning is an important outcome for patients with schizophrenia. To evaluate the effects of paliperidone extended-release (PAL-ER) on social function, symptomatology, and safety in the routine clinical practice, we conducted a 1-year post-marketing surveillance study of PAL-ER. We also explored relationships between symptomatic improvement and socially functional outcome in patients with schizophrenia. PATIENTS AND METHODS: Patients with an established diagnosis of schizophrenia were allowed flexible 3-12 mg/day dosing during the surveillance. Patients were assessed on social functioning using the Social and Occupational Functioning Assessment Scale (SOFAS) and on symptomatology using the Clinical Global Impression-Schizophrenia scale. All adverse events (AEs) were also collected. RESULTS: A total of 1,429 patients were enrolled in the surveillance study, of whom 1,405 were evaluable for safety and 1,142 were evaluable for efficacy. The treatment discontinuation rate for any reason during the observation period was 34.66%. Significant improvements were observed on both Social and Occupational Functioning Assessment Scale and Clinical Global Impression-Schizophrenia scale during the observation period. The percentage of patients with socially functional remission (SOFAS >=61) also increased significantly. A significant association between early improvements in positive symptoms, sex, severity of negative symptoms at baseline, and socially functional remission was observed. A total of 33.52% of patients had AEs and 8.75% of patients had serious AEs. Despite the recommendation of monotherapy with PAL-ER, 65.84% of patients were given additional antipsychotics (polypharmacy). Post hoc comparisons of monotherapy versus polypharmacy revealed that the monotherapy group had better outcomes and fewer AEs than the polypharmacy treated group. The improvement in social functioning and the rate of socially functional remission did not differ between groups. CONCLUSION: PAL-ER treatment showed effective symptom control and improvement in social functioning. The data suggest that early response to antipsychotic treatment should be important for functional outcomes. PMID- 26150723 TI - New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. AB - Despite the discovery and application of many parenteral (unfractionated and low molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs. PMID- 26150724 TI - A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia. AB - Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in class, oral inhibitor of Bruton's tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. PMID- 26150725 TI - A multidisciplinary approach to therapeutic risk management of the suicidal patient. AB - As health care trends toward a system of care approach, providers from various disciplines strive to collaborate to provide optimal care for their patients. While a multidisciplinary approach to suicide risk assessment and management has been identified as important for reducing suicidality, standardized clinical guidelines for such an approach do not yet exist. In this article, the authors propose the adoption of the therapeutic risk management of the suicidal patient (TRMSP) to improve suicide risk assessment and management within multidisciplinary systems of care. The TRMSP, which has been fully articulated in previous articles, involves augmenting clinical risk assessment with structured instruments, stratifying risk in terms of both severity and temporality, and developing and documenting a safety plan. Augmenting clinical risk assessments with reliable and valid structured instruments serves several functions, including ensuring important aspects of suicide are addressed, establishing a baseline for suicidal thoughts and behaviors, facilitating interprofessional communication, and mitigating risk. Similarly, a two-dimensional risk stratification qualifying suicide risk in terms of both severity and temporality can enhance communication across providers and settings and improve understanding of acute crises in the context of chronic risk. Finally, safety planning interventions allow providers and patients to collaboratively create a personally meaningful plan for managing a suicidal crisis that can be continually modified across time with multiple providers in different care settings. In a busy care environment, the TRMSP can provide concrete guidance on conducting clinically and medicolegally sound suicide risk assessment and management. This collaborative and comprehensive process would potentially improve care of patients with suicidality, optimize clinical resources, decrease unnecessary and costly admissions, and mitigate medicolegal risk. The TRMSP may serve as a foundation for building a standardized, collaborative, stepped-care approach that patients, individual providers, and the health care system can all benefit from. PMID- 26150726 TI - Could erlotinib treatment lead to acute cardiovascular events in patients with lung adenocarcinoma after chemotherapy failure? AB - Erlotinib, an epidermal growth factor receptor and tyrosine kinase inhibitor, is a targeted drug that was approved for the treatment of non-small-cell lung cancers and pancreatic cancers. Targeted tyrosine kinase inhibitors are known to have cardiotoxic effects. However, erlotinib does not have a statistically proven effect of increasing acute cardiovascular event (ACE) risk. Preclinical studies showed that beta agonist stimulation among rats that were administered erlotinib led to cardiovascular damage. Thus, there would be an aggregate effect of erlotinib on ACE, although it is not thought to be a cardiotoxic drug itself. In this paper, we present two non-small-cell lung cancer cases that developed ACE under erlotinib treatment. PMID- 26150727 TI - Prognostic role of urokinase plasminogen activator receptor in gastric and colorectal cancer: A systematic review and meta-analysis. AB - PURPOSE: Although the urokinase plasminogen activator receptor (uPAR) is expressed in gastric cancer (GC) and colorectal cancer (CRC), its evaluation as a prognostic biomarker remains controversial. In this study, we performed a literature review and meta-analysis to evaluate the association of uPAR expression with the prognosis of patients with GC and CRC. METHOD: The PubMed database was searched for material published in English, and data were then extracted and assessed by two reviewers independently. Correlations between uPAR expression and clinicopathological features and overall survival (OS) of patients with GC or CRC were analyzed. RESULTS: A total of 2,082 patients with GC and CRC from ten studies were included. The results of the meta-analysis showed that the uPAR expression rate in GC and CRC tissues was higher than that in normal tissues (odds ratio [OR] =3.385; 95% confidence interval [CI] 2.605-4.400; P=0.000). Our meta-analysis also revealed a significant association between uPAR expression and lymph node metastasis (OR =1.366; 95% CI =1.086-1.718; P=0.008) and tumor stage (OR =3.076; 95% CI =2.330-4.061; P=0.000). Furthermore, we found that high uPAR expression correlated with poor OS (OR =1.937; 95% CI =1.570-2.930; P=0.000). CONCLUSION: The uPAR expression may serve as a novel disease marker in GC and CRC, as well as a therapeutic target. PMID- 26150728 TI - Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer. AB - BACKGROUND: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer. METHODS: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG) and Residual Disease in Breast and Nodes (RDBN). RESULTS: Ten patients (11.4%) achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03). MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival. CONCLUSION: MPG and RDBN were similarly related to the patient's prognosis. MPG was more suitable for evaluation of distant disease-free survival, and RDBN was more suitable for evaluation of local recurrence-free survival. Survival following neoadjuvant chemotherapy correlated with the pathological reaction rather than the molecular subtype of breast cancer. The molecular subtype of breast cancer was not correlated with pathological response in patients who did not achieve a pathological complete response. PMID- 26150729 TI - Role of integrin-linked kinase in drug resistance of lung cancer. AB - OBJECTIVE: The objective of the present investigation was to investigate the role of integrin-linked kinase (ILK) in the gemcitabine-resistant lung cancer cell line A549 and explore the underlying mechanism. MATERIALS AND METHODS: Gemcitabine-resistant A549 (A549/GemR) cell line was established by pulse-exposed to moderate concentration of gemcitabine (Gem), and the drug resistant index was measured by MTT assay. Expression of ILK in A549/GemR cell line was detected by Western blot and real-time PCR. An ILK gene-silencing cell line was constructed using lentivirus-coated ILK shRNA. MTT assay was used to detect the drug sensitivity of the A549/GemR cell line to Gem after the ILK gene silencing. Western blot was used to measure the expression of E-cadherin, fibronectin, and MRP1 (multidrug resistance-associated protein 1) after silencing the ILK gene. RESULT: The drug resistance index of A549/GemR was 13.5, and the messenger RNA and protein level of ILK was increased in A549/GemR. IC50 (half maximal inhibitory concentration) decreased from 14.69 to 4.13 mg/L when ILK was knocked down in A549/GemR. The expression of fibronectin and MRP1 was upregulated and E cadherin expression was downregulated in A549/GemR, and these changes were reversed after ILK was knocked down. CONCLUSION: ILK was involved in drug resistance to Gem in lung cancer, and this function may be mediated by epithelial mesenchymal transition and the MRP1 pathway. PMID- 26150730 TI - Association of persistent and transient worsening renal function with mortality risk, readmissions risk, length of stay, and costs in patients hospitalized with acute heart failure. AB - BACKGROUND: Data comparing effects of transient worsening renal function (WRFt) and persistent WRF (WRFp) on outcomes in patients hospitalized with acute heart failure (AHF) are lacking. We determined the characteristics of hospitalized AHF patients who experienced no worsening renal function (non-WRF), WRFt, or WRFp, and the relationship between cohorts and AHF-related outcomes. METHODS AND RESULTS: A patient's first AHF hospitalization (index) was identified in the Cerner Health Facts((r)) database (January 2008-March 2011). Patients had WRF if serum creatinine (SCr) was >=0.3 mg/dL and increased >=25% from baseline, and they were designated as WRFp if present at discharge or WRFt if not present at discharge. A total of 55,436 patients were selected (non-WRF =77%, WRFp =10%, WRFt =13%). WRFp had greater comorbidity burden than WRFt. At index hospitalization, WRFp patients had the highest mortality, whereas WRFt patients had the longest length of stay (LOS) and highest costs. These trends were observed at 30, 180, and 365 days postdischarge and confirmed by multivariable analyses. WRF patients had more AHF-related readmissions than non-WRF patients. In sensitivity analyses of the patient subset with live index hospitalization discharges, postdischarge LOS and costs were highest in WRFt patients, whereas mortality associated with a HF hospitalization was significantly higher for WRF patients vs non-WRF patients, with no difference between WRFp and WRFt. CONCLUSION: In patients hospitalized for AHF, WRFp was associated with the highest mortality, whereas WRFt was associated with the highest LOS and costs. WRF patients had higher readmissions than non-WRF patients. Transient increases in SCr appear to be associated with detrimental outcomes, especially longer LOS and higher costs. PMID- 26150733 TI - Fixed-dose combinations in type 2 diabetes - role of the canagliflozin metformin combination. AB - Canagliflozin-metformin is one of the newest combination therapies available for the treatment of type 2 diabetes mellitus (T2DM). Canagliflozin is an inhibitor of the sodium-glucose co-transporter 2 which causes an increase in the urinary excretion of glucose. In the present article, we review the safety and efficacy of canagliflozin and metformin from data obtained from Phase III metformin add-on therapy clinical trials as there are no studies to date that specifically evaluate the combination of metformin and canagliflozin. Trials included in this review were dual-therapy trials of subjects who were already taking background metformin and were assigned to receive canagliflozin, glimepiride, or sitagliptin. The addition of canagliflozin to metformin resulted in a decrease in HbA1c of 0.73%-0.93%. Canagliflozin 100 mg was considered to be non-inferior to glimepiride and sitagliptin 100 mg with the canagliflozin 300 mg dose being statistically superior to sitagliptin and glimepiride. Other advantages of the use of canagliflozin are reduction in weight (3.3-4.0 kg) and systolic blood pressure (3.3-4.7 mmHg). The primary disadvantages are potential genital mycotic infections, hypotension, and gastrointestinal side effects from metformin. All things considered, this combination appears to be safe and effective in clinical trials and represents a promising option for the treatment of T2DM. PMID- 26150731 TI - Interventions to improve long-term weight loss in patients following bariatric surgery: challenges and solutions. AB - Bariatric surgery aims to provide long-term weight loss and improvement in weight related comorbidities. Unfortunately, some patients do not achieve predicted weight loss targets and many regain a portion of their lost weight within 2-10 years postsurgery. A review of the literature found that behavioral, dietary, psychological, physical, and medical considerations can all play a role in suboptimal long-term weight loss. Recommendations to optimize long-term weight loss include ensuring that the patient understands how the procedure works, preoperative and postoperative education sessions, tailored nutritional supplements, restraint with liquid kilojoules, pureed foods, grazing and eating out of the home, an average of 60 minutes of physical activity per day, and lifelong annual medical, psychological, and dietary assessments. PMID- 26150732 TI - Randomized, double-blind, placebo-controlled, clinical study on the effect of Diabetinol((r)) on glycemic control of subjects with impaired fasting glucose. AB - BACKGROUND: This study investigated the efficacy of Diabetinol((r)) in people with diabetes on medication but not meeting the American Association of Clinical Endocrinologists and American Diabetes Association glycemic, blood pressure, and lipid targets. SUBJECTS AND METHODS: Fifty subjects, aged 18-75 years, with fasting blood glucose <=15.4 mmol/L, hemoglobin A1c levels <=12%, and a body mass index between 25 and 40 kg/m(2), were enrolled in a 24-week, randomized, double blind, placebo-controlled, parallel study. Diabetinol((r)) or placebo was administered as 2*525 mg capsules/day. RESULTS: In the Diabetinol((r)) group, 14.3% versus 0% in the placebo group, 33.3% versus 15.4% in placebo, 20.0% versus 12.5% in placebo, and 83.3% versus 60% in placebo achieved the American Association of Clinical Endocrinologists and American Diabetes Association targets for hemoglobin A1c, low-density lipoprotein, total cholesterol, and systolic blood pressure, respectively. There was no difference in the maximum concentration (Cmax) of serum glucose or area under the curve (AUC)0-240 minutes. The time to Cmax was longer for participants on Diabetinol((r)) than placebo group at week 12 (P=0.01). Fasting blood glucose increased from baseline to week 24 in both groups; however, this increase was 14.3 mg/dL lower in the Diabetinol((r)) group versus placebo. The Diabetinol((r)) group showed an increase of 5.53 mg/dL in fasting insulin at week 12 (P=0.09) and 3.2 mg/dL at week 24 (P=0.41) over and above the placebo group. A decrease of 1.5% in total cholesterol, 5.8% in low-density lipoprotein, and a 1.6% increase in high-density lipoprotein concentrations were seen in the Diabetinol((r)) group. Diabetinol((r)) improved 6-month oral glucose tolerance test and 2-hour postprandial glucose profiles in participants between 40 and 60 years of age. CONCLUSION: The current study suggests a role for Diabetinol((r)) as an adjunctive therapy for glycemic maintenance and for decreasing the risk of diabetes-associated comorbidities in type 2 diabetic patients on conventional therapies. PMID- 26150734 TI - Successful creation of an anemia management algorithm for hemodialysis patients. AB - INTRODUCTION: Several anemia guidelines for hemodialysis patients have recommended a target hemoglobin (Hb) range of 10-12 g/dL. However, maintaining Hb values continuously within a narrow target has been difficult, and there has been no generally accepted anemia management algorithm for hemodialysis patients. METHODS: In our study, we created an anemia management algorithm that considers the length of erythrocyte lifetimes, focuses on the combination of erythropoiesis stimulating agent management and iron administration, and prevents iron deficiency and overload. Our algorithm established a target Hb range of 10-12 g/dL. RESULTS: We evaluated our algorithm in 49 patients for 6 months. The mean Hb values were approximately 11 g/dL during our study period. The percentage of patients in the target Hb range of 10-12 g/dL increased from 77.6% (38 of 49) at baseline to 85.7% (42 of 49) at 4-6 months. Throughout monthly regular blood tests during 1-6 months after we introduced our algorithm, Hb values remained within the target range in 55.1% (27 of 49) of patients. The standard deviation of Hb values significantly decreased at 5 and 6 months (P=0.013 and P=0.047, respectively; 1 g/dL at 0 month, 0.7 g/dL at 5 months, and 0.7 g/dL at 6 months). Our algorithm also succeeded in suppressing cumulative doses of iron (<=800 mg) and decreasing the ferritin values significantly (P=0.011). There were no significant differences in erythropoiesis-stimulating agent doses between 0 and 6 months (P=0.357). CONCLUSION: Our anemia management algorithm successfully increased the number of patients in the target Hb range, significantly decreased the Hb standard deviation, suppressed cumulative doses of iron, and decreased ferritin values. These results suggest a better prognosis for hemodialysis patients. Further studies are required to evaluate our algorithm. PMID- 26150735 TI - Treatment of metastatic colorectal cancer: focus on panitumumab. AB - Targeted agents are an important therapeutic option in the treatment of metastatic colorectal cancer (mCRC). Panitumumab is a recombinant, fully humanized, immunoglobulin G2 monoclonal antibody that targets the epidermal growth factor receptor (EGFR) with efficacy in mCRC as monotherapy and in combination with chemotherapy. Kirsten rat sarcoma (KRAS) mutation status has emerged as an important biomarker to predict response to anti-EGFR therapy. Optimal timing for panitumumab use in the mCRC treatment algorithm has not been established. This review discusses the mechanism of action, predictive biomarkers, and role of panitumumab in the treatment of mCRC. PMID- 26150736 TI - Reliability and validity of a dual-task test for skill proficiency in roundhouse kicks in elite taekwondo athletes. AB - The dual-task methodology, conducting two tasks simultaneously, may provide better validity than the traditional single-task tests in the environment that is closely related to real sport competitions. The purpose of this study is to determine the reliability and validity of a dual-task test that aims to measure the reaction time and skill proficiency in roundhouse kicks in elite and sub elite taekwondo athletes. The dual-task results were compared to those in the single-task movements with various levels of complexity. The single-task movements A, B, and C were composed of one, three, and five roundhouse kicks, respectively. The dual-task movement D was composed of movement C and a push of a button in response to a light stimulus as the secondary task. The subjects were 12 elite and 12 sub-elite male taekwondo athletes. The test included four movements with five repeats of each movement in a randomized order. Each subject conducted the same test on two consecutive days. The intraclass correlation coefficient (ICC) showed moderate-to-high correlation in the premotor time (ICC =0.439-0.634 in elite and ICC =0.681-0.824 in sub-elite), motor time (ICC =0.861 0.956 in elite and ICC =0.721-0.931 in sub-elite), and reaction time (ICC =0.692 in elite and ICC =0.676 in sub-elite) in the secondary task in both groups. The elite athletes had significantly faster premotor time than their sub-elite counterparts in all the four movements (all P<0.05). The largest difference lies in the reaction time in the secondary task, in which the elite group (0.248+/ 0.026 seconds) was 33.0% faster than the sub-elite group (0.370+/-0.081 seconds) (P<0.001). This study shows that the test developed in this study has reasonable reliability and validity in both single- and dual-task methods. In addition, the dual-task method may be a more appropriate way to assess the reaction time and skill proficiency in taekwondo athletes. PMID- 26150737 TI - Relationship between performance test and body composition/physical strength characteristic in sprint canoe and kayak paddlers. AB - OBJECTIVE: Canoe sprint is divided into canoe and kayak. The difference between the two competitions is in physical performance. The aim of the present study was to compare and investigate the relationship between physical characteristics and fitness between the two canoe sprint competitors. METHODS: Subjects were 11 canoe paddlers (C) and 12 kayak paddlers (K). They underwent anthropometric characteristics, body composition and fitness tests, and 120 s all-out tests using a canoe and kayak ergometer. The unpaired t-test was used to test for significant differences between disciplines, while Pearson's correlation coefficient was used to examine the association between each measurement item and the performance test. RESULTS: The age, height, body mass, body mass index, and total body fat were, C: 20.6+/-0.9 yr, 172.8+/-5.2 cm, 70.8+/-7.8 kg, 23.7+/-1.9, 14.4%+/-3.5%; and K: 19.7+/-1.2 yr, 172.8+/-5.3 cm, 69.5+/-7.8 kg, 23.2+/-2.1, 12.1%+/-3.6%, respectively. No significant differences were seen in any of the items for physical characteristics or fitness between C and K. A correlation analysis of performance tests and each measurement item revealed a positive correlation with low-speed isokinetic knee extension and flexion strength for C only (extension: r=0.761; flexion: r=0.784; P<0.01). In addition, performance tests were positively correlated with the circumference of arm (upper arm: r=0.876; forearm: r=0.820; P<0.01) and lower limb (thigh: r=0.781; calf: r=0.753; P<0.01) in C and with height (r=0.549, P<0.05), arm span (r=0.639, P<0.05), and leg length (r=0.621, P<0.01) in K. CONCLUSION: We suggest that the factors correlating with the performance test differ depending on the competitions. PMID- 26150738 TI - Toward a more professional and practical medical education: a novel Central European approach. AB - We here present an innovative curriculum for a complete medical education that conforms to the current European Bologna system of academic training. The curriculum aims at raising doctors who are excellently prepared for clinical work over as short a time as 5 years; it provides a comprehensive, yet shorter than usual, education that strongly pronounces the importance of increasing the students' practical clinical competences and rigorously excludes superfluous contents. The curriculum encompasses 52 modules, 32 at the bachelor's and 20 at the master's level. Already at the level of the bachelor degree, full employability is given; the students finish the master's course as medical doctors optimally prepared to manage patients at the level of postgraduate medical education. The structure of the curriculum is modular; each modular component is essential for medical education and contains an average of five European Credit Transfer System credits, amounting to 150 hours of education. Depending on the subspecialty, the courses include lectures, seminars, practical laboratory training, and clinical training at varying quantities. In addition to attendance times, sufficient time slots are prepared for self-study in lectures, seminars, and practical work. With our curriculum, we provide an easily applicable backbone for a modern course of medicine that can be installed also at smaller academic institutions. PMID- 26150739 TI - How can undergraduate ophthalmology teaching be improved? PMID- 26150741 TI - Prediction and characterization of microRNAs from eleven fish species by computational methods. AB - MicroRNAs (miRNAs) are a family of single-stranded RNA molecules about 22 nt in length, which can regulate protein-coding gene expression in various organisms by post-transcriptional repression of messenger. In this research, the potential miRNAs and their target genes were analyzed and predicted by computational methods from the EST and GSS databases of eleven fish species, 43 potential miRNAs were identified, they belong to 38 miRNA families, some miRNAs are highly conserved in animal kingdom, the predicted target genes are involved in development, signal transduction, response to environmental stress and pathogen invasion. Taken together, our data suggest that there are a plentiful of miRNAs in these eleven fish species, these miRNAs may play some important roles by regulating their target genes, and the data provide important information for further functional studies. PMID- 26150742 TI - Morphological and molecular profiling of Spirogyra from northeastern and northern Thailand using inter simple sequence repeat (ISSR) markers. AB - Green algae, Spirogyra (Chlorophyta), are found in a wide range of habitats including small stagnant water bodies, rivers, and streams. Species identification of Spirogyra based on morphological characteristics has proven to be a difficult process. An accurate identification method is required to evaluate genetic variations. This study is aimed at investigating the molecular profiling of 19 samples of Spirogyra from northern and northeastern Thailand. The morphological characteristics of each sample were recorded, viz. cell dimensions (width and length), along with the number and arrangement of chloroplast spirals/pyrenoids. With regard to a correlation of the biological and ecological parameters, conductivity was clearly significantly related to the number of pyrenoids. While DO is negatively related to the number of chloroplast spirals. Molecular studies with 10 ISSR primers were amplified to examine the DNA fingerprints. Morphological characters were determined to be significantly different by revealing 5 traits (P < 0.05) for all specimens. In addition, the DNA markers of all specimens were investigated using 10 ISSR primers. The results show that the PCR technique amplified 108 fragments. An analysis of the DNA fragments grouped all samples by ISRR-PCR, which were then separated into two groups according to their distribution. PMID- 26150740 TI - BRAF gene: From human cancers to developmental syndromes. AB - The BRAF gene encodes for a serine/threonine protein kinase that participates in the MAPK/ERK signalling pathway and plays a vital role in cancers and developmental syndromes (RASopathies). The current review discusses the clinical significance of the BRAF gene and other members of RAS/RAF cascade in human cancers and RAS/MAPK syndromes, and focuses the molecular basis and clinical genetics of BRAF to better understand its parallel involvement in both tumourigenesis and RAS/MAPK syndromes-Noonan syndrome, cardio-facio-cutaneous syndrome and LEOPARD syndrome. PMID- 26150743 TI - Biological activities of two macroalgae from Adriatic coast of Montenegro. AB - In the present investigation the acetone extracts of macroalgae Ulva lactuca and Enteromorpha intestinalis were tested for antioxidant, antimicrobial and cytotoxic potential. Antioxidant activity was evaluated by measuring the scavenging capacity of tested samples on DPPH and superoxide anion radicals, reducing the power of samples and determination of total phenolic and flavonoid compounds in extracts. As a result of the study, U. lactuca extract was found to have a better free radical scavenging activity (IC50 = 623.58 MUg/ml) than E. intestinalis extract (IC50 = 732.12 MUg/ml). Moreover, the tested extracts had effective ferric reducing power and superoxide anion radical scavenging. The total content of phenol in extracts of U. lactuca and E. intestinalis was 58.15 and 40.68 MUg PE/mg, while concentrations of flavonoids were 39.58 and 21.74 MUg RE/mg, respectively. Furthermore, among the tested species, extracts of U. lactuca showed a better antimicrobial activity with minimum inhibitory concentration values ranging from 0.156 to 5 mg/ml, but it was relatively weak in comparison with standard antibiotics. Bacillus mycoides and Bacillus subtilis were the most susceptible to the tested extracts. Contrary to this Aspergillus flavus, Aspergillus fumigatus and Penicillium purpurescens were the most resistant. Finally, cytotoxic activity of tested extracts was evaluated on four human cancer cell lines. Extract of E. intestinalis expressed the stronger cytotoxic activity towards all tested cell lines with IC50 values ranging from 74.73 to 155.39 MUg/ml. PMID- 26150744 TI - Effect of different exposed lights on quercetin and quercetin glucoside content in onion (Allium cepa L.). AB - Quercetin and quercetin glucosides are the major flavonols present in onion (Allium cepa L.) and are predominantly present as quercetin, quercetin-3,4' diglucoside and quercetin-4'-glucoside. Effect of different light wavelengths on onion after harvest and storage, with fluorescent, blue, red and ultra violet light influenced the quercetin and quercetin glucosides profile. In a peeled onion, all the light treatments elevated quercetin content in bulb. Among them, particularly fluorescent light effect was more eminent which stimulates the maximum synthesis of quercetin in onion. In case of whole onion bulb, skin and pulp showed different responses to light treatment, respectively. The pulp had the highest quercetin glucosides under blue light, whereas the lowest under fluorescent light. Onion skin showed nearly opposite pattern as compared to the pulp. In particular, light treatment proved to be a better way to increase the level of quercetin content in onions which might be utilized for industrial production of bioactive compounds from onion and onion waste products. PMID- 26150745 TI - Antibiotic resistance modulation by natural products obtained from Nasutitermes corniger (Motschulsky, 1855) and its nest. AB - Insects and their products are included in the traditional pharmacopoeia of various ethnic groups worldwide. In the Brazilian semiarid region can be highlighted the use of the termite Nasutitermes corniger for the treatment of various diseases. This study evaluated the ethanol extract of N. corniger and its nest as an antimicrobial agent and as a modulator of bacterial resistance against multidrug strains. The Minimum Inhibitory Concentration (MIC) of the extract on Staphylococcus aureus and Escherichia coli by microdilution was determined, as well as MIC of antibiotics in the presence and absence of extract. Despite having no significant antimicrobial activity (MIC ? 1000 MUg mL(-1)), the extract showed additive activity to the antibiotic efficacy, significantly reducing its MIC. These results suggest that N. corniger and its nest are promising natural products for use in antimicrobial therapy. PMID- 26150746 TI - Elicitation with abiotic stresses improves pro-health constituents, antioxidant potential and nutritional quality of lentil sprouts. AB - Phenolic content and antioxidant potential of lentil sprouts may be enhanced by treatment of seedlings in abiotic stress conditions without any negative influence on nutritional quality. The health-relevant and nutritional quality of sprouts was improved by elicitation of 2-day-old sprouts with oxidative, osmotic, ion-osmotic and temperature stresses. Among the sprouts studied, those obtained by elicitation with osmotic (600 mM mannitol) and ion-osmotic (300 mM NaCl) shocks had the highest total phenolic content levels: 6.52 and 6.56 mg/g flour, respectively. Oxidative stress significantly enhanced the levels of (+)-catechin and p-coumaric acid. A marked elevation of the chlorogenic and gallic acid contents was also determined for sprouts induced at 4 degrees C and 40 degrees C. The elevated phenolic content was translated into the antioxidant potential of sprouts, especially the ability to reduce lipid oxidation. A marked elevation of this ability was determined for seedlings treated with 20 mM, 200 mM H2O2 (oxidative stress) and 600 mM mannitol (osmotic stress); about a 12-fold, 8-fold and 9.5-fold increase in respect to control sprouts. The highest ability to quench free radicals was observed in sprouts induced by osmotic stress (IC50- 4.91 and 5.12 mg/ml for 200 mM and 600 mM mannitol, respectively). The highest total antioxidant activity indexes were determined for sprouts elicited with 20 mM H2O2 and 600 mM mannitol: 4.0 and 3.4, respectively. All studied growth conditions, except induction at 40 degrees C, caused a significant elevation of resistant starch levels which was also affected in a subsequent reduction of starch digestibility. Improvement of sprout quality by elicitation with abiotic stresses is a cheap and easy biotechnology and it seems to be an alternative to conventional techniques applied to improve the health promoting phytochemical levels and bioactivity of low-processed food. PMID- 26150747 TI - Molecular cloning and expression analysis of RrNHX1 and RrVHA-c genes related to salt tolerance in wild Rosa rugosa. AB - Salt stress is one important factor influencing the growth and development of plants, and salt tolerance of plants is a result of combined action of multiple genes and mechanisms. Rosa rugosa is not only an important ornamental plant, but also the natural aromatic plant of high value. Wild R. rugosa which is naturally distributed on the coast and islands of China has a good salt tolerance due to the special living environment. Here, the vacuolar Na(+)/H(+) reverse transporter gene (NHX1) and the vacuolar H(+)-ATPase subunit C gene (VHA-c) closely related to plant salt tolerance were isolated from wild R. rugosa, and the expression patterns in R. rugosa leaves of the two genes under NaCl stress were determined by real-time quantitative fluorescence PCR. The results showed that the RrNHX1 protein is a constitutive Na(+)/H(+) reverse transporter, the expression of the RrNHX1 gene first increased and then decreased with the increasing salt concentration, and had a time-controlled effect. The RrVHA-c gene is suggestive of the housekeeping feature, its expression pattern showed a similar variation trend with the RrNHX1 gene under the stress of different concentrations of NaCl, and its temporal expression level under 200 mM NaCl stress presented bimodal change. These findings indicated that RrNHX1 and RrVHA-c genes are closely associated with the salt tolerance trait of wild R. rugosa. PMID- 26150748 TI - Prevalence of ESBL and MBL encoding genes in Acinetobacter baumannii strains isolated from patients of intensive care units (ICU). AB - The aim of this study was to investigate the prevalence of ESBL and MBL encoding genes among A. baumannii isolates. In this cross sectional study, 100 A. baumannii strains were isolated from ICU wards of 3 educational hospitals of Hamadan City, Iran in 2011. Phenotypic identification of the production of ESBLs and MBLs has been carried out by using E-test and DDST methods, respectively. PCR technique was used for amplification of the ESBL and MBL encoding genes, namely: CTX-M, SHV, TEM, OXA-51, VIM-Family, IMP-Family, SPM-1, SIM-1, and GIM-1. Eighty seven (87%), 95 (95%), 98 (98%) and 95 (95%) out of 100 A. baumannii isolates were resistant to imipenem, meropenem, ceftazidime and cefotaxime, respectively. Also, 99% and 7% of the isolates were MBLs and ESBLs produced phenotypically. Thirty (30%), 20 (20%) and 58 (58%) out of 100 A. baumannii isolates have been confirmed to harbor the bla VIM-family, TEM and SHV genes, respectively. Our results show no significant relationship between the detected gens with production of MBLs and ESBLs in spite of high prevalence of MBL encoding and drug resistant A. baumannii. Probably some other genes rather than what we studied are involved in phenotypic production of MBLs and ESBLs and subsequent drug resistance in Hamadan area, Iran. PMID- 26150749 TI - Effects of open grazing and livestock exclusion on floristic composition and diversity in natural ecosystem of Western Saudi Arabia. AB - Livestock grazing is one of the main causes of rangeland degradation in Saudi Arabia. Fencing to exclude grazers is one of the main management practices used to restore vegetation and conserve biodiversity. The main objectives of this study were to investigate the changes in plant diversity and abundance, floristic composition and plant groups of the major life forms in response to thirty-five years of grazing exclosure in western Saudi Arabia. These vegetation attributes and palatability were compared in 30 sampling stands located in the excluded and grazed sites. Our results showed that livestock exclusion significantly increased covers, density and species richness of annuals, grasses, perennial forbs, shrubs and trees. Exclosure enhanced the abundance and richness of palatable species and depressed the development of weedy species. About 66.7% of the recorded species at the excluded site were highly palatable compared to 34.5% at the grazed site. In contrary, about 55.2% unpalatable species were found in the grazed site compared to 25.8% in the protected site. Jaccard's similarity index between the excluded and grazed sites showed lower values of 0.39%, 0.40% and 0.31% at levels of families, genus and species, respectively. The results suggest that establishing livestock exclusion may be a useful sustainable management tool for vegetation restoration and conservation of plant diversity in degraded rangelands of arid regions. PMID- 26150750 TI - Molecular and serotyping characterization of shiga toxogenic Escherichia coli associated with food collected from Saudi Arabia. AB - Shiga toxin-producing Escherichia coli (STEC) strains are considered as one of the major food-borne disease agents in humans worldwide. STEC strains, also called verotoxin-producing E. coli strains. The objectives of the present study were serotyping and molecular characterization of shiga toxigenic E. coli associated with raw meat and milk samples collected from Riyadh, Saudi Arabia. A total of 540 milk samples were collected from 5 dairy farms and 150 raw meat samples were collected from different abattoirs located in Riyadh, Saudi Arabia. E. coli were recovered from 86 milk samples (15.93%), serotyping of E. coli isolates revealed, 26 (4.81%) strains O157: H7, 23 (4.26%) strains O111, 20 (3.70%) strains O113: H21, 10 (1.85%) strains O22: H8 and 7 (1.3%) strains O172: H21. Meanwhile, 17 (11.33%) strains of E. coli were recovered from raw meat samples, serotyping of E. coli isolates revealed, 6 (4%) strains O157: H7, 5 (3.33%) strains O111 and 4 (2.67%) strains O174: H2 and only two (1.33%) strains were identified as O22: H8. Shiga toxin2 was detected in 58 (67.44%) serotypes of E. coli recovered from milk samples and 16 (94.12%) serotypes of E. coli recovered from meat samples, while intimin gene was detected in 38 (44.186%) serotypes of E. coli recovered from milk samples and in 10 (58.82%) serotypes of E. coli recovered from meat samples. The results of this study revealed the efficiency of combination between serotyping and molecular typing of E. coli isolates recovered from food of animal origin for rapid detection and characterization of STEC. PMID- 26150751 TI - Seasonal variations in the body composition and bioaccumulation of heavy metals in Nile tilapia collected from drainage canals in Al-Ahsa, Saudi Arabia. AB - The body composition of Nile tilapia (Oreochromis niloticus) collected from drainage canals in Al-Ahsa, Saudi Arabia and the concentration of four heavy metals; zinc (Zn), cadmium (Cd), cobalt (Co) and lead (Pb) in both fish muscles and the water collected from this environment were assessed across the four seasons. The body composition was found to change with the seasons, with the best body composition being recorded in autumn and winter, where higher levels of protein (17.24, 17.65%), and fat (0.58, 0.71%) and lower water content (80.15, 79.86%) respectively were noted. The concentration of heavy metals in both fish muscles and the water body also varied significantly with the seasons. In the fish muscles, the highest content of Zn (0.409 mg/kg dry weight) and Cd (4.140 mg/kg dry weight) was recorded in winter, however, the highest concentration of Co (0.318 mg/kg dry weight) and Pb (1.96 mg/kg dry weight) was observed in spring and summer respectively. On the other hand, the water samples collected in autumn showed the maximum concentration of Cd (1.385 mg/L), Co (0.762 mg/L) and Pb (0.18 mg/L) however, the maximum concentration of Zn (0.0041 mg/L) was recorded in winter. With the exception of Cd, the accumulation of the studied heavy metals in fish muscles was within the safe limits for seafood recommended by various organizations. PMID- 26150752 TI - Chemokine receptors expression on peripheral CD4-lymphocytes in rheumatoid arthritis: Coexpression of CCR7 and CD95 is associated with disease activity. AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation triggered by infiltrating CD4 lymphocytes. The positioning and activation of lymphocyte in inflamed synovial tissues are dependent on a number of factors including their chemokine receptor expression profile. We aimed to investigate which chemokine receptors pattern correlate with serum cytokine levels and with disease activity. Forty patients with RA (34 female and 6 male) with age range from 21 to 68 years were included. Twenty healthy volunteers (16 female and 4 male) with matched age (range 21-48 years) were served as healthy controls (HCs). Expression of chemokine receptors (CCR5, CX3CR1 and CCR7) together with the apoptosis-related marker (CD95) was analyzed using three-color flow cytometry analysis after gating on CD4(+) peripheral blood lymphocytes. Plasma levels of IL-6, IL-10, IL-12 and TNF-alpha cytokines were measured in all participants using ELISA. Disease activity score (DAS28-CRP) system was assessed and active disease was defined as DAS28 ?3.2. Twenty-five (62.4%) patients were classified as active RA (ARA) and 15 (37.5%) patients with inactive RA (IRA). Percentages of CD4(+) lymphocytes expressing CD95 with either of CCR7 or CCR5 were significantly higher in ARA compared to IRA and HCs groups, while the expression of CX3CR1 on T-cells was found significantly lower in both CD95(-) and CD95(+) T-cells in RA groups than HC. Percentages of CD4(+)CD95(+)CCR7(+) cells correlated positively with IL-6 (r = 0.390). Whereas CD4(+)CD95(+)CX3CR1(+) were negatively correlated with TNF-alpha (r = -0.261). Correlation of CD4(+)CD95(+)CCR7(+) T cell subset with disease activity and inflammatory cytokines suggests a role for this cell subset in the pathogenesis of RA. Further investigation will be required to fully characterize this cell subset and its role in disease progression. PMID- 26150753 TI - Population fluctuation and vertical distribution of meiofauna in the Red Sea interstitial environment. AB - The composition and distribution of the benthic meiofauna assemblages of the Egyptian coasts along the Red Sea are described in relation to abiotic variables. Sediment samples were collected seasonally from three stations chosen along the Red Sea to observe the meiofaunal community structure, its temporal distribution and vertical fluctuation in relation to environmental conditions of the Red Sea marine ecosystem. The temperature, salinity, pH, dissolved oxygen, and redox potential were measured at the time of collection. The water content of the sediments, total organic matters and chlorophyll a values were determined, and sediment samples were subjected to granulometric analysis. A total of 10 meiofauna taxa were identified, with the meiofauna being primarily represented by nematodes (on annual average from 42% to 84%), harpacticoids, polycheates and ostracodes; and the meiofauna abundances ranging from 41 to 167 ind./10 cm(2). The meiofaunal population density fluctuated seasonally with a peak of 192.52 ind./10 cm(2) during summer at station II. The vertical zonation in the distribution of meiofaunal community was significantly correlated with interstitial water, chlorophyll a and total organic matter values. The present study indicates the existence of the well diversified meiofaunal group which can serve as food for higher trophic levels in the Red Sea interstitial environment. PMID- 26150754 TI - Isolation and characterization of biosurfactant production under extreme environmental conditions by alkali-halo-thermophilic bacteria from Saudi Arabia. AB - Twenty three morphologically distinct microbial colonies were isolated from soil and sea water samples, which were collected from Jeddah region, Saudi Arabia for screening of the most potent biosurfactant strains. The isolated bacteria were selected by using different methods as drop collapse test, oil displacement test, blue agar test, blood hemolysis test, emulsification activity and surface tension. The results showed that the ability of Virgibacillus salarius to grow and reduce surface tension under a wide range of pH, salinities and temperatures gives bacteria isolate an advantage in many applications such as pharmaceutical, cosmetics, food industries and bioremediation in marine environment. The biosurfactant production by V. salarius decreased surface tension and emulsifying activity (30 mN/m and 80%, respectively). In addition to reducing the production cost of biosurfactants by tested several plant-derived oils such as jatropha oil, castor oils, jojoba oil, canola oil and cottonseed oil. In this respect the feasibility to reusing old frying oil of sunflower for production rhamnolipids and sophorolipids, their use that lead to solve many ecological and industrial problems. PMID- 26150755 TI - Improvement of halophilic cellulase production from locally isolated fungal strain. AB - Halophilic cellulases from the newly isolated fungus, Aspergillus terreus UniMAP AA-6 were found to be useful for in situ saccharification of ionic liquids treated lignocelluloses. Efforts have been taken to improve the enzyme production through statistical optimization approach namely Plackett-Burman design and the Face Centered Central Composite Design (FCCCD). Plackett-Burman experimental design was used to screen the medium components and process conditions. It was found that carboxymethylcellulose (CMC), FeSO4.7H2O, NaCl, MgSO4.7H2O, peptone, agitation speed and inoculum size significantly influence the production of halophilic cellulase. On the other hand, KH2PO4, KOH, yeast extract and temperature had a negative effect on enzyme production. Further optimization through FCCCD revealed that the optimization approach improved halophilic cellulase production from 0.029 U/ml to 0.0625 U/ml, which was approximately 2.2 times greater than before optimization. PMID- 26150756 TI - Apoptotic properties of polysaccharide isolated from fruiting bodies of medicinal mushroom Fomes fomentarius in human lung carcinoma cell line. AB - Mushrooms are known to complement chemotherapy and radiation therapy by countering the side effects of cancer. Recently, there has been great interest in isolation of novel bioactive compounds from mushrooms due to their numerous health beneficial effects. Chemically water-extractable polysaccharide (MFKF AP1beta), with a molecular weight of 12 kDa, was isolated from fruiting bodies of mushroom Fomes fomentarius. In this research, we investigated the anti-tumor effects of MFKF-AP1beta on human lung carcinoma A549 cells. Results showed that MFKF-AP1beta markedly inhibited A549 cell growth in a dose-dependent manner based on the amount of lactate dehydrogenase (LDH) released and morphological alterations. In addition, MFKF-AP1beta induced cellular apoptosis by causing single-stranded DNA breakage, as evidenced by apoptosis assay. Furthermore, MFKF AP1beta (25-100 MUg/ml) significantly induced single-stranded DNA breakage in A549 cells, as shown by comet assay. Taken together, our results demonstrate that MFKF-AP1beta has strong anti-tumor effects mediated through induction of apoptosis. Therefore, MFKF-AP1beta could be useful in lung chemotherapy. PMID- 26150757 TI - Trapping of Saker Falcon Falco cherrug and Peregrine Falcon Falco peregrinus in Saudi Arabia: Implications for biodiversity conservation. AB - The numbers of Falco cherrug and Falco peregrinus trapped during their migration over the Kingdom of Saudi Arabia (KSA) were investigated from published reports and through interviews with well-known trappers and dealers over several years (1989-2013). The number of trapped individuals increased for both species over a 23 year period, which is probably related to an enhanced trapping effort. Time series analysis suggests that the number of Saker Falcons being trapped is likely to be stable with annual fluctuations in the coming ten-year period, whereas the number of trapped Peregrine Falcons will probably decline with a small fluctuation initially. Using the population viability analysis suggests a high extinction rate for the Saker Falcon population migrating through KSA during the coming 10 and 20 years; whereas Peregrine Falcons probably take more than 100 years to reach the extinction threshold. However, the increase in the trapping period, especially in the spring, that has been observed during the last five years could increase the number of falcons trapped in the future. As both falcon species are migratory, implementing conservation actions across all range states is important to ensure a favourable conservation status for the Saker and Peregrine Falcons. Both species will benefit through the implementation of the Global Action Plan (GAP), developed by the Saker Falcon Task Force. PMID- 26150758 TI - Conocarpus biochar as a soil amendment for reducing heavy metal availability and uptake by maize plants. AB - The objective of this study was to assess the use of Concarpus biochar as a soil amendment for reducing heavy metal accessibility and uptake by maize plants (Zea mays L.). The impacts of biochar rates (0.0, 1.0, 3.0, and 5.0% w/w) and two soil moisture levels (75% and 100% of field capacity, FC) on immobilization and availability of Fe, Mn, Zn, Cd, Cu and Pb to maize plants as well as its application effects on soil pH, EC, bulk density, and moisture content were evaluated using heavy metal-contaminated soil collected from mining area. The biochar addition significantly decreased the bulk density and increased moisture content of soil. Applying biochar significantly reduced NH4OAc- or AB-DTPA extractable heavy metal concentrations of soils, indicating metal immobilization. Conocarpus biochar increased shoot dry biomass of maize plants by 54.5-102% at 75% FC and 133-266% at 100% FC. Moreover, applying biochar significantly reduced shoot heavy metal concentrations in maize plants (except for Fe at 75% FC) in response to increasing application rates, with a highest decrease of 51.3% and 60.5% for Mn, 28% and 21.2% for Zn, 60% and 29.5% for Cu, 53.2% and 47.2% for Cd at soil moisture levels of 75% FC and 100% FC, respectively. The results suggest that biochar may be effectively used as a soil amendment for heavy metal immobilization and in reducing its phytotoxicity. PMID- 26150759 TI - The role of soluble fibrin during anticoagulant therapy: a case report. AB - Warfarin, dabigatran, and apixaban are used for preventing ischemic stroke due to non-valvular atrial fibrillation (NVAF). However, it is often challenging to select the appropriate anticoagulant. We present the case of a 70-year-old male patient with persistent NVAF who developed pulmonary thromboembolism (PTE), deep vein thrombosis (DVT), and left atrial thrombus during anticoagulant therapy with warfarin. Intravenous recombinant tissue plasminogen activator was administered during his acute PTE. Heparin and apixaban were administered over 28 days; heparin was discontinued after the DVT resolved, while apixaban was administered to prevent ischemic stroke. Two days after heparin was discontinued, the patient experienced an ischemic stroke. Dabigatran was administered for secondary ischemic stroke prevention. Soluble fibrin (SF) levels remained elevated during treatment with heparin and apixaban and returned to normal after apixaban was replaced with dabigatran. Monitoring of SF may be useful as an index for selection of anticoagulants. PMID- 26150760 TI - Does it matter who organises your health care? AB - BACKGROUND: As the prevalence of long-term and multimorbid conditions is increasing, patients increasingly require consultations with multiple health care professionals and coordination of their care needs. METHODS: This study is based on a 2011 survey of older Australians which draws on sub-populations of people with diabetes aged 50 years or over, people with chronic obstructive pulmonary disease, and members of Nationals Seniors Australia. We develop a composite coordination measure and examine differences in the measure with different care coordination indicators using both descriptive and regression methods. Three categories of respondent-perceived care organisers are used: health care professionals; "no one"; and patients, their partner, relative or friend. RESULTS: Of the 2,540 survey respondents (an overall response rate of 24%), 1,865 provided information on who organised their health care, and composite coordination measures were calculated for 1,614. Multivariate analysis showed the composite score was highest where a health care professional coordinated care, followed by care organised by self or a carer, and then the group reporting no organiser. CONCLUSION: In moving towards care coordination there are opportunities to improve the care coordination process itself, and the key enablers to improving care coordination appear to be the availability and communication of clinical information and the role of the clinical team. PMID- 26150762 TI - Health economics and integrated care: a growing and challenging relationship. PMID- 26150761 TI - Do patients with long-term side effects of cancer treatment benefit from general practitioner support? A literature review. AB - BACKGROUND: Alongside specialist cancer clinics, general practitioners have an important role in cancer patients' follow-up care, yet no literature summarises the nature, extent and impact of their involvement. This paper addresses this issue through a review of the literature. METHODS: Studies were sourced from six academic databases - AustHealth (n = 202), CINAHL (n = 500), the Cochrane Library (reviews and trials; n = 200), Embase (n = 368), PHCRIS (n = 132) and PubMed/Medline (n = 410). Studies that focused on interventions designed for patients receiving follow-up care and reported cancer care provided by a general practitioner delivered alongside specialist care were reviewed. RESULTS: A total of 19 papers were identified as relevant for this review (3 randomised control trials; 4 cross-sectional, 5 cohort and 3 qualitative studies, and 3 systematic reviews). The reviewed studies indicated that providing general practitioner-led supportive interventions for post-treatment care of cancer patients is feasible and acceptable to patients. General practitioner involvement resulted in improved physical and psychosocial well-being of patients and continuity of care, especially for patients with concomitant health conditions. CONCLUSION: Involving general practitioners in post-treatment cancer care is beneficial to patients. However, proactive initiatives that encourage and facilitate patients to consult their general practitioner about their needs or symptoms of recurrence should be considered. PMID- 26150763 TI - Chronic and integrated care in Catalonia. AB - INTRODUCTION: The Chronicity Prevention and Care Programme set up by the Health Plan for Catalonia 2011-2015 has been an outstanding and excellent opportunity to create a new integrated care model in Catalonia. People with chronic conditions require major changes and transformation within the current health and social system. The new and gradual context of ageing, increase in the number of chronic diseases and the current fragmented system requires this transformation to be implemented. METHOD: The Chronicity Prevention and Care Programme aims to implement actions which drive the current system towards a new scenario where organisations and professionals must work collaboratively. New tools should facilitate this new context- or work-like integrated health information systems, an integrative financing and commissioning scheme and provide a new approach to virtual care by substituting traditional face-to-face care with transfer and shared responsibilities between patients, citizens and health care professionals. RESULTS: It has been observed some impact reducing the rate of emergency admissions and readmission related to chronic conditions and better outcome related to better chronic disease control. Some initiative like the Catalan Expert Patient Program has obtained good results and an appropriate service utilization. DISCUSSION: The implementation of a Chronic Care Program show good results but it is expected that the new integrated health and social care agenda could provoke a real change and transformation. Some of the results related to better health outcomes and a decrease in avoidable hospital admissions related to chronic conditions confirm we are on the right track to make our health and social system more sustainable for the decades to come. PMID- 26150764 TI - Building integrated care systems: a case study of Bidasoa Integrated Health Organisation. AB - INTRODUCTION: This paper analyses the implementation of integrated care policies in the Basque Country through the deployment of an Integrated Health Organisation in Bidasoa area during the period 2011-2014. Structural, functional and clinical integration policies have been employed with the aim to deliver integrated and person-centred care for patients, especially for those living with chronic conditions. METHODS: This organisational case study used multiple data sources and methods in a pragmatic and reflexive manner to build a picture of the organisational development over a 4-year period. In order to measure the progress of integration three concepts have been measured: (i) readiness for chronicity measured with Assessment of Readiness for Chronicity in Healthcare Organisations tool; (ii) collaboration between clinicians from different care levels measured with the D'Amour Questionnaire, and (iii) overall impact of integration through several indicators based on the Triple Aim Framework. RESULTS: The measurement of organisational readiness for chronicity showed improvements in five of the six areas under evaluation. Similarly the collaboration between professionals of different care levels showed a steady improvement in each of the 10 items. Furthermore, the Triple Aim-based indicators showed a better experience of care in terms of patients' perceptions of care coordination; a reduction in hospital utilisation, particularly for patients with complex chronic conditions; and cost containment in terms of per capita expenditure. CONCLUSION: There is a significant amount of data that shows that Bidasoa Integrated Health Organisation has progressed in terms of delivering integrated care for chronic conditions with a positive impact on several Triple Aim outcomes. PMID- 26150765 TI - The common characteristics and outcomes of multidisciplinary collaboration in primary health care: a systematic literature review. AB - INTRODUCTION: Research on collaboration in primary care focuses on specific diseases or types of collaboration. We investigate the effects of such collaboration by bringing together the results of scientific studies. THEORY AND METHODS: We conducted a systematic literature review of PubMed, CINAHL, Cochrane and EMBASE. The review was restricted to publications that test outcomes of multidisciplinary collaboration in primary care in high-income countries. A conceptual model is used to structure the analysis. RESULTS: Fifty-one studies comply with the selection criteria about collaboration in primary care. Approximately half of the 139 outcomes in these studies is non-significant. Studies among older patients, in particular, report non-significant outcomes (p < .05). By contrast, a higher proportion of significant results were found in studies that report on clinical outcomes. CONCLUSIONS AND DISCUSSION: This review shows a large diversity in the types of collaboration in primary care; and also thus a large proportion of outcomes do not seem to be positively affected by collaboration. Both the characteristics of the structure of the collaboration and the collaboration processes themselves affect the outcomes. More research is necessary to understand the mechanism behind the success of collaboration, especially on the exact nature of collaboration and the context in which collaboration takes place. PMID- 26150766 TI - Better experiences with quality of care predict well-being of patients with chronic obstructive pulmonary disease in the Netherlands. AB - OBJECTIVE: This study was conducted to (1) identify improvements in care quality and well-being of patients with chronic obstructive pulmonary disease in the Netherlands and (2) investigate the longitudinal relationship between these factors. METHODS: This longitudinal study was conducted among patients diagnosed with chronic obstructive pulmonary disease enrolled in the Kennemer Lucht care programme in the Netherlands. Biomarker data (lung capacity) were collected at patients' health care practices in 2012. Complete case analysis was conducted, and the multiple imputation technique allowed us to report pooled results from imputed datasets. RESULTS: Surveys were filled out by 548/1303 (42%) patients at T0 (2012) and 569/996 (57%) remaining participants at T1. Quality of care improved significantly (p < 0.05). Analyses adjusted for well-being at T0, age, educational level, marital status, gender, lung function and health behaviours showed that patients' assessments of the quality of chronic care delivery at T0 (p < 0.01) and changes therein (p < 0.001) predicted patients' well-being at T1. CONCLUSION: These results clearly show that the quality of care and changes therein are important for the well-being of patients with chronic obstructive pulmonary disease in the primary care setting. PRACTICE IMPLICATIONS: To improve quality of care for chronically ill patients, multicomponent interventions may be needed. PMID- 26150768 TI - Case study: auditory brain responses in a minimally verbal child with autism and cerebral palsy. AB - An estimated 30% of individuals with autism spectrum disorders (ASD) remain minimally verbal into late childhood, but research on cognition and brain function in ASD focuses almost exclusively on those with good or only moderately impaired language. Here we present a case study investigating auditory processing of GM, a nonverbal child with ASD and cerebral palsy. At the age of 8 years, GM was tested using magnetoencephalography (MEG) whilst passively listening to speech sounds and complex tones. Where typically developing children and verbal autistic children all demonstrated similar brain responses to speech and nonspeech sounds, GM produced much stronger responses to nonspeech than speech, particularly in the 65-165 ms (M50/M100) time window post-stimulus onset. GM was retested aged 10 years using electroencephalography (EEG) whilst passively listening to pure tone stimuli. Consistent with her MEG response to complex tones, GM showed an unusually early and strong response to pure tones in her EEG responses. The consistency of the MEG and EEG data in this single case study demonstrate both the potential and the feasibility of these methods in the study of minimally verbal children with ASD. Further research is required to determine whether GM's atypical auditory responses are characteristic of other minimally verbal children with ASD or of other individuals with cerebral palsy. PMID- 26150767 TI - The role of maternal obesity in the risk of neuropsychiatric disorders. AB - Recent evidence indicates that perinatal exposure to maternal obesity, metabolic disease, including diabetes and hypertension, and unhealthy maternal diet has a long-term impact on offspring behavior and physiology. During the past three decades, the prevalence of both obesity and neuropsychiatric disorders has rapidly increased. Epidemiologic studies provide evidence that maternal obesity and metabolic complications increase the risk of attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, anxiety, depression, schizophrenia, eating disorders (food addiction, anorexia nervosa, and bulimia nervosa), and impairments in cognition in offspring. Animal models of maternal high-fat diet (HFD) induced obesity also document persistent changes in offspring behavior and impairments in critical neural circuitry. Animals exposed to maternal obesity and HFD consumption display hyperactivity, impairments in social behavior, increased anxiety-like and depressive-like behaviors, substance addiction, food addiction, and diminished cognition. During development, these offspring are exposed to elevated levels of nutrients (fatty acids, glucose), hormones (leptin, insulin), and inflammatory factors (C-reactive protein, interleukin, and tumor necrosis factor). Such factors appear to permanently change neuroendocrine regulation and brain development in offspring. In addition, inflammation of the offspring brain during gestation impairs the development of neural pathways critical in the regulation of behavior, such as serotoninergic, dopaminergic, and melanocortinergic systems. Dysregulation of these circuits increases the risk of mental health disorders. Given the high rates of obesity in most developed nations, it is critical that the mechanisms by which maternal obesity programs offspring behavior are thoroughly characterized. Such knowledge will be critical in the development of preventative strategies and therapeutic interventions. PMID- 26150769 TI - Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration. AB - Elevation of intracellular cyclic AMP (cAMP) levels has proven to be one of the most effective means of overcoming inhibition of axonal regeneration by myelin associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein. Pharmacological manipulation of cAMP through the administration of dibutyryl cAMP or rolipram leads to enhanced axonal growth both in vivo and in vitro, and importantly, upregulation of cAMP within dorsal root ganglion neurons is responsible for the conditioning lesion effect, which indicates that cAMP plays a significant role in the endogenous mechanisms that promote axonal regeneration. The effects of cAMP are transcription-dependent and are mediated through the activation of protein kinase A (PKA) and the transcription factor cyclic AMP response element binding protein (CREB). This leads to the induction of a variety of genes, several of which have been shown to overcome myelin-mediated inhibition in their own right. In this review, we will highlight the pro-regenerative effects of arginase I (ArgI), interleukin (IL)-6, secretory leukocyte protease inhibitor (SLPI), and metallothionein (MT)-I/II, and discuss their potential for therapeutic use in spinal cord injury. PMID- 26150771 TI - Corrigendum: TGF-beta1 promotes cerebral cortex radial glia-astrocyte differentiation in vivo. AB - [This corrects the article on p. 393 in vol. 8, PMID: 25484855.]. PMID- 26150770 TI - Recurrent seizure-like events are associated with coupled astroglial synchronization. AB - Increasing evidence suggest that astrocytes significantly modulate neuronal function at the level of the tripartite synapse both in physiological and pathophysiological conditions. The global control of the astrocytic syncytium over neuronal networks, however, is still less recognized. Here we examined astrocytic signaling during epileptiform activity which is generally attributed to large-scale neuronal synchronization. We show that seizure-like events in the low-[Mg(2+)] in vitro epilepsy model initiate massive, long-range astrocytic synchronization which is spatiotemporally coupled to the synchronized neuronal activity reaching its maximum at the electrographic tonic/clonic transition. Cross-correlation analysis of neuronal and astrocytic Ca(2+) signaling demonstrates that high degree of synchronization arises not only among astrocytes, but also between neuronal and astrocyte populations, manifesting in astrocytic seizure-like events. We further show that astrocytic gap junction proteins contribute to astrocytic synchronization since their inhibition by carbenoxolone (CBX) or Cx43 antibody increased the interictal interval and in 41% of slices completely prevented recurrent seizure-like activity. In addition, CBX also induced unsynchronized Ca(2+) transients associated with decreasing incidence of epileptiform discharges afterwards. We propose therefore that local, unsynchronized astrocytic Ca(2+) transients inhibit, while long-range, synchronized Ca(2+) signaling contributes to the propagation of recurrent seizure like events. PMID- 26150772 TI - Social preferences and cognitive reflection: evidence from a dictator game experiment. AB - This paper provides experimental evidence on the relationship between social preferences and cognitive abilities, which we measure using the Cognitive Reflection Test (CRT). We elicit social preferences by way of 24 dictatorial situations, in which the Dictator's choice sets include (i) standard Dictator games, where increasing the Dictator's payoff yields a loss for the Recipient, (ii) efficient Dictator games, where increasing the Dictator's payoff also increases that the Recipient's; as well as other situations in which (iii) either the Dictator's or (iv) the Recipient's monetary payoff is held constant. We partition our subject pool into three groups: reflective (scoring 2 or more in the CRT), impulsive (opting twice or more for the "intuitive" but wrong answers in the CRT) and the remainder. We find that impulsive Dictators show a marked inequity aversion attitude, especially in standard Dictator Games. By contrast, reflective Dictators show lower distributional concerns, except for the situations in which the Dictators' payoff is held constant. In this case, reflective Dictators give significantly more. PMID- 26150773 TI - Generalization of socially transmitted and instructed avoidance. AB - Excessive avoidance behavior, in which an instrumental action prevents an upcoming aversive event, is a defining feature of anxiety disorders. Left unchecked, both fear and avoidance of potentially threatening stimuli may generalize to perceptually related stimuli and situations. The behavioral consequences of generalization mean that aversive learning experiences with specific threats may lead to the inference that classes of related stimuli are threatening, potentially dangerous, and need to be avoided, despite differences in physical form. Little is known however about avoidance generalization in humans and the learning pathways by which it may be transmitted. In the present study, we compared two pathways to avoidance-instructions and social observation on subsequent generalization of avoidance behavior, fear expectancy and physiological arousal. Participants first learned that one cue was a danger cue (conditioned stimulus, CS+) and another was a safety cue (CS-). Groups were then either instructed that a simple avoidance response in the presence of the CS+ cancelled upcoming shock (instructed-learning group) or observed a short movie showing a demonstrator performing the avoidance response to prevent shock (observational-learning group). During generalization testing, danger and safety cues were presented along with generalization stimuli that parametrically varied in perceptual similarity to the CS+. Reinstatement of fear and avoidance was also tested. Findings demonstrate, for the first time, generalization of socially transmitted and instructed avoidance: both groups showed comparable generalization gradients in fear expectancy, avoidance behavior and arousal. Return of fear was evident, suggesting that generalized avoidance remains persistent following extinction testing. The utility of the present paradigm for research on avoidance generalization is discussed. PMID- 26150774 TI - No strings attached: physiological monitoring of rhesus monkeys (Macaca mulatta) with thermal imaging. AB - Methodological challenges make physiological affective observations very restrictive as in many cases they take place in a laboratory setting rather than the animals' natural habitat. In the current study using Infrared Thermal Imaging we examine the physiological thermal imprints of five macaques. The monkeys were exposed in three different experimental scenarios. Playing with a toy, food teasing as well as feeding. It was observed that during teasing the temperature of the region surrounding the eyes was higher than play as a result of rapid saccades directed at the food. Compared to play and teasing, a lower temperature accompanied feeding on the upper lip, nose and orbital region suggesting elevated levels of distress. These findings prove that thermal imaging is a reliable method of physiological monitoring the subject at a distance while preserving a semi-experimental setting. PMID- 26150775 TI - AMPA Receptor-mTOR Activation is Required for the Antidepressant-Like Effects of Sarcosine during the Forced Swim Test in Rats: Insertion of AMPA Receptor may Play a Role. AB - Sarcosine, an endogenous amino acid, is a competitive inhibitor of the type I glycine transporter and an N-methyl-d-aspartate receptor (NMDAR) coagonist. Recently, we found that sarcosine, an NMDAR enhancer, can improve depression related behaviors in rodents and humans. This result differs from previous studies, which have reported antidepressant effects of NMDAR antagonists. The mechanisms underlying the therapeutic response of sarcosine remain unknown. This study examines the role of mammalian target of rapamycin (mTOR) signaling and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) activation, which are involved in the antidepressant-like effects of several glutamatergic system modulators. The effects of sarcosine in a forced swim test (FST) and the expression levels of phosphorylated mTOR signaling proteins were examined in the absence or presence of mTOR and AMPAR inhibitors. In addition, the influence of sarcosine on AMPAR trafficking was determined by analyzing the phosphorylation of AMPAR subunit GluR1 at the PKA site (often considered an indicator for GluR1 membrane insertion in neurons). A single injection of sarcosine exhibited antidepressant-like effects in rats in the FST and rapidly activated the mTOR signaling pathway, which were significantly blocked by mTOR inhibitor rapamycin or the AMPAR inhibitor 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) pretreatment. Moreover, NBQX pretreatment eliminated the ability of sarcosine to stimulate the phosphorylated mTOR signaling proteins. Furthermore, GluR1 phosphorylation at its PKA site was significantly increased after an acute in vivo sarcosine treatment. The results demonstrated that sarcosine exerts antidepressant-like effects by enhancing AMPAR-mTOR signaling pathway activity and facilitating AMPAR membrane insertion. Highlights-A single injection of sarcosine rapidly exerted antidepressant-like effects with a concomitant increase in the activation of the mammalian target of rapamycin mTOR signaling pathway. The antidepressant-like effects of sarcosine occur through the activated AMPAR mTOR signaling pathway.-Sarcosine could enhance AMPAR membrane insertion via an AMPAR throughput. PMID- 26150776 TI - Fronto-temporal white matter connectivity predicts reversal learning errors. AB - Each day, we make hundreds of decisions. In some instances, these decisions are guided by our innate needs; in other instances they are guided by memory. Probabilistic reversal learning tasks exemplify the close relationship between decision making and memory, as subjects are exposed to repeated pairings of a stimulus choice with a reward or punishment outcome. After stimulus-outcome associations have been learned, the associated reward contingencies are reversed, and participants are not immediately aware of this reversal. Individual differences in the tendency to choose the previously rewarded stimulus reveal differences in the tendency to make poorly considered, inflexible choices. Lesion studies have strongly linked reversal learning performance to the functioning of the orbitofrontal cortex, the hippocampus, and in some instances, the amygdala. Here, we asked whether individual differences in the microstructure of the uncinate fasciculus, a white matter tract that connects anterior and medial temporal lobe regions to the orbitofrontal cortex, predict reversal learning performance. Diffusion tensor imaging and behavioral paradigms were used to examine this relationship in 33 healthy young adults. The results of tractography revealed a significant negative relationship between reversal learning performance and uncinate axial diffusivity, but no such relationship was demonstrated in a control tract, the inferior longitudinal fasciculus. Our findings suggest that the uncinate might serve to integrate associations stored in the anterior and medial temporal lobes with expectations about expected value based on feedback history, computed in the orbitofrontal cortex. PMID- 26150777 TI - Influence of sleep disorders on the behavior of individuals with autism spectrum disorder. AB - The aim of this study was to investigate the correlation between sleep disorders and the behavior of subjects with autism spectrum disorder (ASD) and control subjects using specific questionnaires. A small percentage (1.8%) of the control subjects had symptoms indicative of sleep-breathing disorders (SBD) and nocturnal sweating. Fifty-nine percent of the subjects with ASD had symptoms indicative of at least one sleep disorder, with SBD the most commonly reported (38%). In the control group, the symptoms of SBD were correlated with social, thought, attentional, aggression, externalizing and behavioral problems. In the ASD group, disorders of arousal (DA) were correlated with thinking problems, and disorders of excessive somnolence were correlated with thinking and behavioral problems. These results suggest that children and adolescents with ASD have a high frequency of sleep disorders, which in turn correlate with some of the behavioral traits that they already exhibit. Furthermore, sleep disturbances, when present in the typically developing children, also correlated with behavioral problems. PMID- 26150779 TI - Alexithymia modulates the experience of the rubber hand illusion. AB - Alexithymia is associated with lower awareness of emotional and non-emotional internal bodily signals. However, evidence suggesting that alexithymia modulates body awareness at an external level is scarce. This study aimed to investigate whether alexithymia is associated with disrupted multisensory integration by using the rubber hand illusion task. Fifty healthy individuals completed the Toronto Alexithymia Scale and underwent the rubber hand illusion measure. In this measure, one watches a rubber hand being stroked synchronously or asynchronously with one's own hand, which is hidden from view. Compared to the asynchronous stimulation, the synchronous stimulation results in the illusion that the rubber hand and the participant's hand are closer together than they really are and that the rubber hand belongs to them. Results revealed that higher levels of alexithymia are associated with a lower ownership illusion over the rubber hand. In conclusion, our findings demonstrate that high alexithymia scorers integrate two simultaneous sensory and proprioceptive events into a single experience (lower multisensory integration) to a lesser extent than low alexithymia scorers. Higher susceptibility to the illusion in high alexithymia scorers may indicate that alexithymia is associated with an abnormal focus of one's own body. PMID- 26150778 TI - Stable and variable affordances are both automatic and flexible. AB - The mere observation of pictures or words referring to manipulable objects is sufficient to evoke their affordances since objects and their nouns elicit components of appropriate motor programs associated with object interaction. While nobody doubts that objects actually evoke motor information, the degree of automaticity of this activation has been recently disputed. Recent evidence has indeed revealed that affordances activation is flexibly modulated by the task and by the physical and social context. It is therefore crucial to understand whether these results challenge previous evidence showing that motor information is activated independently from the task. The context and the task can indeed act as an early or late filter. We will review recent data consistent with the notion that objects automatically elicit multiple affordances and that top-down processes select among them probably inhibiting motor information that is not consistent with behavior goals. We will therefore argue that automaticity and flexibility of affordances are not in conflict. We will also discuss how language can incorporate affordances showing similarities, but also differences, between the motor information elicited by vision and language. Finally we will show how the distinction between stable and variable affordances can accommodate all these effects. PMID- 26150780 TI - Decoding covert shifts of attention induced by ambiguous visuospatial cues. AB - Simple and unambiguous visual cues (e.g., an arrow) can be used to trigger covert shifts of visual attention away from the center of gaze. The processing of visual stimuli is enhanced at the attended location. Covert shifts of attention modulate the power of cerebral oscillations in the alpha band over parietal and occipital regions. These modulations are sufficiently robust to be decoded on a single trial basis from electroencephalography (EEG) signals. It is often assumed that covert attention shifts are under voluntary control, and that they also occur in more natural and complex environments, but there is no direct evidence to support this assumption. We address this important issue by using random-dot stimuli to cue one of two opposite locations, where a visual target is presented. We contrast two conditions, one in which the random-dot motion is predictive of the target location, and the other, in which it provides ambiguous information. Behavioral results show attention shifts in anticipation of the visual target, in both conditions. In addition, using the common spatial patterns (CSPs) algorithm, we extract EEG power features in the alpha-band (around 10 Hz) that best discriminate the attended location in single trials. We obtain a significant decoding accuracy in 7/10 subjects using a cross-validation procedure applied in the predictive condition. Interestingly, similar accuracy (significant in 5/10 subjects) is obtained when the CSPs trained in the predictive condition are tested in the ambiguous condition. In agreement with this result, we find that the CSPs show very similar topographies in both conditions. These results shed a new light on the behavioral and EEG correlates of visuospatial attention in complex visual environments. This study demonstrates that alpha-power features could be used in brain-computer interfaces to decode covert attention shifts in an environment containing ambiguous spatial information. PMID- 26150781 TI - Depression of corticomotor excitability after muscle fatigue induced by electrical stimulation and voluntary contraction. AB - In this study, we examined the effect of muscle fatigue induced by tetanic electrical stimulation (ES) and submaximal isometric contraction on corticomotor excitability. Experiments were performed in a cross-over design. Motor-evoked potentials (MEPs) were elicited by transcranial magnetic stimulation (TMS). Corticomotor excitability was recorded before and after thumb opposition muscle fatigue tasks, in which 10% of the maximal tension intensity was induced by tetanic ES or voluntary contraction (VC). The participants were 10 healthy individuals who performed each task for 10 min. Surface electrodes placed over the abductor pollicis brevis (APB) muscle recorded MEPs. F- and M-waves were elicited from APB by supramaximal ES of the median nerve. After the tetanic ES- and VC tasks, MEP amplitudes were significantly lower than before the task. However, F- and M-wave amplitudes remained unchanged. These findings suggest that corticospinal excitability is reduced by muscle fatigue as a result of intracortical inhibitory mechanisms. Our results also suggest that corticomotor excitability is reduced by muscle fatigue caused by both VC and tetanic ES. PMID- 26150783 TI - The time between intention and action affects the experience of action. AB - We present a study investigating how the delay between the intention to act and the following action, influenced the experience of action. In experiments investigating sense of agency and experience of action, the contrast is most often between voluntary and involuntary actions. It is rarely asked whether different types of intentions influence the experience of action differently. To investigate this we distinguished between proximal intentions (i.e., intentions for immediate actions) and delayed intentions (i.e., intentions with a temporal delay between intention and action). The distinction was implemented in an intentional binding paradigm, by varying the delay between the time where participants formed the intention to act and the time at which they performed the action. The results showed that delayed intentions were followed by a stronger binding effect for the tone following the action compared to proximal intentions. The actions were reported to have occurred earlier for delayed intentions than for proximal intentions. This effect was independent of the binding effect usually found in intentional binding experiments. This suggests that two perceptual shifts occurred in the contrast between delayed intentions and proximal intentions: The first being the binding effect, the second a general shift in the perceived time of action. Neither the stronger binding effect for tone, nor the earlier reports of action, differed across delays for delayed intentions. The results imply that delayed intentions and proximal intentions have a different impact on the experience of action. PMID- 26150782 TI - Observation and imitation of actions performed by humans, androids, and robots: an EMG study. AB - Understanding others' actions is essential for functioning in the physical and social world. In the past two decades research has shown that action perception involves the motor system, supporting theories that we understand others' behavior via embodied motor simulation. Recently, empirical approach to action perception has been facilitated by using well-controlled artificial stimuli, such as robots. One broad question this approach can address is what aspects of similarity between the observer and the observed agent facilitate motor simulation. Since humans have evolved among other humans and animals, using artificial stimuli such as robots allows us to probe whether our social perceptual systems are specifically tuned to process other biological entities. In this study, we used humanoid robots with different degrees of human-likeness in appearance and motion along with electromyography (EMG) to measure muscle activity in participants' arms while they either observed or imitated videos of three agents produce actions with their right arm. The agents were a Human (biological appearance and motion), a Robot (mechanical appearance and motion), and an Android (biological appearance and mechanical motion). Right arm muscle activity increased when participants imitated all agents. Increased muscle activation was found also in the stationary arm both during imitation and observation. Furthermore, muscle activity was sensitive to motion dynamics: activity was significantly stronger for imitation of the human than both mechanical agents. There was also a relationship between the dynamics of the muscle activity and motion dynamics in stimuli. Overall our data indicate that motor simulation is not limited to observation and imitation of agents with a biological appearance, but is also found for robots. However we also found sensitivity to human motion in the EMG responses. Combining data from multiple methods allows us to obtain a more complete picture of action understanding and the underlying neural computations. PMID- 26150784 TI - Effects of homeostatic constraints on associative memory storage and synaptic connectivity of cortical circuits. AB - The impact of learning and long-term memory storage on synaptic connectivity is not completely understood. In this study, we examine the effects of associative learning on synaptic connectivity in adult cortical circuits by hypothesizing that these circuits function in a steady-state, in which the memory capacity of a circuit is maximal and learning must be accompanied by forgetting. Steady-state circuits should be characterized by unique connectivity features. To uncover such features we developed a biologically constrained, exactly solvable model of associative memory storage. The model is applicable to networks of multiple excitatory and inhibitory neuron classes and can account for homeostatic constraints on the number and the overall weight of functional connections received by each neuron. The results show that in spite of a large number of neuron classes, functional connections between potentially connected cells are realized with less than 50% probability if the presynaptic cell is excitatory and generally a much greater probability if it is inhibitory. We also find that constraining the overall weight of presynaptic connections leads to Gaussian connection weight distributions that are truncated at zero. In contrast, constraining the total number of functional presynaptic connections leads to non Gaussian distributions, in which weak connections are absent. These theoretical predictions are compared with a large dataset of published experimental studies reporting amplitudes of unitary postsynaptic potentials and probabilities of connections between various classes of excitatory and inhibitory neurons in the cerebellum, neocortex, and hippocampus. PMID- 26150785 TI - The PREP pipeline: standardized preprocessing for large-scale EEG analysis. AB - The technology to collect brain imaging and physiological measures has become portable and ubiquitous, opening the possibility of large-scale analysis of real world human imaging. By its nature, such data is large and complex, making automated processing essential. This paper shows how lack of attention to the very early stages of an EEG preprocessing pipeline can reduce the signal-to-noise ratio and introduce unwanted artifacts into the data, particularly for computations done in single precision. We demonstrate that ordinary average referencing improves the signal-to-noise ratio, but that noisy channels can contaminate the results. We also show that identification of noisy channels depends on the reference and examine the complex interaction of filtering, noisy channel identification, and referencing. We introduce a multi-stage robust referencing scheme to deal with the noisy channel-reference interaction. We propose a standardized early-stage EEG processing pipeline (PREP) and discuss the application of the pipeline to more than 600 EEG datasets. The pipeline includes an automatically generated report for each dataset processed. Users can download the PREP pipeline as a freely available MATLAB library from http://eegstudy.org/prepcode. PMID- 26150786 TI - Distribution and effects of the muscarinic receptor subtypes in the primary visual cortex. AB - Muscarinic cholinergic receptors modulate the activity and plasticity of the visual cortex. Muscarinic receptors are divided into five subtypes that are not homogeneously distributed throughout the cortical layers and cells types. This distribution results in complex action of the muscarinic receptors in the integration of visual stimuli. Selective activation of the different subtypes can either strengthen or weaken cortical connectivity (e.g., thalamocortical vs. corticocortical), i.e., it can influence the processing of certain stimuli over others. Moreover, muscarinic receptors differentially modulate some functional properties of neurons during experience-dependent activity and cognitive processes and they contribute to the fine-tuning of visual processing. These functions are involved in the mechanisms of attention, maturation and learning in the visual cortex. This minireview describes the anatomo-functional aspects of muscarinic modulation of the primary visual cortex's (V1) microcircuitry. PMID- 26150788 TI - Aging and wisdom: age-related changes in economic and social decision making. AB - World life expectancy is increasing and many populations will begin to age rapidly. The impeding prevalence of a greater number of older people living longer lives will have significant social and economic implications. It is important to understand how older people make economic and social decisions. Aging can be associated with a "phenomenon of decline" and also greater wisdom. This paper seeks to examine the relationship between wisdom and aging. It reviews and connects the behavioral sciences and neuroscience literature on age differences in the following social and economic decision making domains that represent subcomponents of wisdom: (1) prosocial behavior in experimental economic games and competitive situations; (2) resolving social conflicts; (3) emotional homeostasis; (4) self-reflection; (5) dealing effectively with uncertainty in the domains of risk, ambiguity and intertemporal choice. Overall, we find a lack of research into how older people make economic and social decisions. There is, however, some evidence that older adults outperform young adults on certain subcomponents of wisdom, but the exact relationship between old age and each subcomponent remains unclear. A better understanding of these relationships holds the potential to alleviate a wide range of mental health problems, and has broad implications for social policies aimed at the elderly. PMID- 26150789 TI - MTSET modification of D4S6 cysteines stabilize the fast inactivated state of Nav1.5 sodium channels. AB - The transmembrane S6 segments of Na(+) sodium channels form the cytoplasmic entrance of the channel and line the internal aspects of the aqueous pore. This region of the channel has been implicated in Na(+) channel permeation, gating, and pharmacology. In this study we utilized cysteine substitutions and methanethiosulfonate reagent (MTSET) to investigate the role of the S6 segment of homologous domain 4 (D4S6) in the gating of the cardiac (Nav1.5) channel. D4S6 cysteine mutants were heterologously expressed in tsA201 cells and currents recorded using whole-cell patch clamp. Internal MTSET reduced the peak Na(+) currents, induced hyperpolarizing shifts in steady-state inactivation and slowed the recovery of mutant channels with cysteines inserted near the middle (F1760C, V1763C) and C-terminus (Y1767C) of the D4S6. These findings suggested a link between the MTSET inhibition and fast inactivation. This was confirmed by expressing the V1763C and Y1767C mutations in non-inactivating Nav1.5 channels. Removing inactivation abolished the MTSET inhibition of the V1763C and Y1767C mutants. The data indicate that the MTSET-induced reduction in current primarily results from slower recovery from inactivation that produces hyperpolarizing shifts in fast inactivation and decreases the steady-state availability of the channels. This contrasted with a cysteine inserted near the C-terminus of the D4S6 (I1770C) where MTSET increased the persistent Na(+) current at depolarized voltages consistent with impaired fast inactivation. Covalent modification of D4S6 cysteines with MTSET adduct appears to reduce the mobility of the D4S6 segment and stabilize the channels in the fast inactivated state. These findings indicate that residues located near the middle and C-terminus of the D4S6 play an important role in fast inactivation. PMID- 26150790 TI - Personalized medicine for pathological circadian dysfunctions. AB - The recent approval of a therapeutic for a circadian disorder has increased interest in developing additional medicines for disorders characterized by circadian disruption. However, previous experience demonstrates that drug development for central nervous system (CNS) disorders has a high failure rate. Personalized medicine, or the approach to identifying the right treatment for the right patient, has recently become the standard for drug development in the oncology field. In addition to utilizing Companion Diagnostics (CDx) that identify specific genetic biomarkers to prescribe certain targeted therapies, patient profiling is regularly used to enrich for a responsive patient population during clinical trials, resulting in fewer patients required for statistical significance and a higher rate of success for demonstrating efficacy and hence receiving approval for the drug. This personalized medicine approach may be one mechanism that could reduce the high clinical trial failure rate in the development of CNS drugs. This review will discuss current circadian trials, the history of personalized medicine in oncology, lessons learned from a recently approved circadian therapeutic, and how personalized medicine can be tailored for use in future clinical trials for circadian disorders to ultimately lead to the approval of more therapeutics for patients suffering from circadian abnormalities. PMID- 26150792 TI - The management of turn transition in signed interaction through the lens of overlaps. AB - There have been relatively few studies on sign language interaction carried out within the framework of conversation analysis (CA). Therefore, questions remain open about how the basic building blocks of social interaction such as turn, turn construction unit (TCU) and turn transition relevance place (TRP) can be understood and analyzed in sign language interaction. Recent studies have shown that signers regularly fine-tune their turn-beginnings to potential completion points of turns (Groeber, 2014; Groeber and Pochon-Berger, 2014; De Vos et al., 2015). Moreover, signers deploy practices for overlap resolution as in spoken interaction (McCleary and Leite, 2013). While these studies have highlighted the signers' orientation to the "one-at-a-time" principle described by Sacks et al. (1974), the present article adds to this line of research by investigating in more detail those sequential environments where overlaps occur. The contribution provides an overview of different types of overlap with a focus of the overlap's onset with regard to a current signer's turn. On the basis of a 33-min video recording of a multi-party interaction between 4 female signers in Swiss German Sign Language (DSGS), the paper provides evidence for the orderliness of overlapping signing. Furthermore, the contribution demonstrates how participants collaborate in the situated construction of turns as a dynamic and emergent gestalt and how they interactionally achieve turn transition. Thereby the study adds to recent research in spoken and in signed interaction that proposes to rethink turn boundaries and turn transition as flexible and interactionally achieved. PMID- 26150791 TI - Ion channel regulation by phosphoinositides analyzed with VSPs-PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility. AB - The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K(+) channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs. PMID- 26150787 TI - Oxidized cholesterol as the driving force behind the development of Alzheimer's disease. AB - Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid Abeta peptides and neurofibrillary tangles (NFT) within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism. The brain's high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes. The chronic inflammatory events observed in the AD brain include activation of microglia and astrocytes, together with enhancement of inflammatory molecule and free radical release. Along with glial cells, neurons themselves have been found to contribute to neuroinflammation in the AD brain, by serving as sources of inflammatory mediators. Oxidative stress is intimately associated with neuroinflammation, and a vicious circle has been found to connect oxidative stress and inflammation in AD. Alongside oxidative stress and inflammation, altered cholesterol metabolism and hypercholesterolemia also significantly contribute to neuronal damage and to progression of AD. Increasing evidence is now consolidating the hypothesis that oxidized cholesterol is the driving force behind the development of AD, and that oxysterols are the link connecting the disease to altered cholesterol metabolism in the brain and hypercholesterolemia; this is because of the ability of oxysterols, unlike cholesterol, to cross the blood brain barrier (BBB). The key role of oxysterols in AD pathogenesis has been strongly supported by research pointing to their involvement in modulating neuroinflammation, Abeta accumulation, and cell death. This review highlights the key role played by cholesterol and oxysterols in the brain in AD pathogenesis. PMID- 26150793 TI - Differential effects of bilingualism and culture on early attention: a longitudinal study in the U.S., Argentina, and Vietnam. AB - A large body of literature suggests that bilingualism strongly influences attentional processes among a variety of age groups. Increasing studies, however, indicate that culture may also have measurable effects on attentional processes. Bilinguals are often exposed to multiple cultural backgrounds, therefore, it is unclear if being exposed to multiple languages and culture together influence attentional processes, or if the effect themselves are uniquely linked to different attentional processes. The present study explores the relevancy of different attentional processes-alerting, orienting, and executive control-to language and to culture. In the present study, 97 3-years-old (Mean age = 38.78 months) monolingual and bilingual children from three countries (the U.S., Argentina, and Vietnam) were longitudinally tested for a total of five time points on a commonly used non-linguistic attentional paradigm-the Attention Network Test. Results demonstrate that when other factors are controlled (e.g., socio-economic status, vocabulary knowledge, age), culture plays an important role on the development of the alerting and executive control attentional network, while language status was only significant on the executive control attentional network. The present study indicates that culture may interact with bilingualism to further explain previous reported advantages, as well as elucidate the increasing disparity surrounding cognitive advantages in bilingual literature. PMID- 26150794 TI - Emotional intelligence and recovering from induced negative emotional state. AB - The aim of the present study was to examine the relationship between emotional intelligence (EI) and recovering from negative emotions induction, using a performance test to measure EI. Sixty seven undergraduates participated in the procedure, which lasted 75 min and was divided into three stages. At Time 1, subjects answered the State-Trait Anxiety Inventory (STAI)-S, Profile of Mood States (POMS)-A, and EI was assessed by Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). At Time 2, negative emotions were induced by nine pictures taken from the International Affective Picture System and participants were asked to complete a second STAI-S and POMS-B questionnaires. At Time 3 participants were allowed to rest doing a distracting task and participants were asked to complete a third STAI-S and POMS-A questionnaires. Results showed that the branches of the MSCEIT emotional facilitation and emotional understanding are related to previous mood states and mood recovery, but not to mood reactivity. This finding contrasts nicely with studies on which emotional recovery was assessed in relation to EI self-reported measures, highlighting the perception and emotional regulation. PMID- 26150795 TI - Who does Red Bull give wings to? Sensation seeking moderates sensitivity to subliminal advertisement. AB - This study assessed whether subliminal priming of a brand name of a drink can affect people's choices for the primed brand, and whether this effect is moderated by personality traits. Participants with different levels of sensation seeking were presented subliminally with the words Red Bull or Lde Ublr. Results revealed that being exposed to Red Bull lead on average to small increases in participants' preferences for the primed brand. However, this effect was twice as strong for participants high in sensation seeking and did not occur for participants low in sensation seeking. Going beyond previous research showing that situational factors (e.g., thirst, fatigue...) can increase people's sensitivity to subliminal advertisement, our results suggest that some dispositional factors could have the same potentiating effect. These findings highlight the necessity of taking personality into account in non-conscious persuasion research. PMID- 26150796 TI - Cognitive penetrability and emotion recognition in human facial expressions. AB - Do our background beliefs, desires, and mental images influence our perceptual experience of the emotions of others? In this paper, we will address the possibility of cognitive penetration (CP) of perceptual experience in the domain of social cognition. In particular, we focus on emotion recognition based on the visual experience of facial expressions. After introducing the current debate on CP, we review examples of perceptual adaptation for facial expressions of emotion. This evidence supports the idea that facial expressions are perceptually processed as wholes. That is, the perceptual system integrates lower-level facial features, such as eyebrow orientation, mouth angle etc., into facial compounds. We then present additional experimental evidence showing that in some cases, emotion recognition on the basis of facial expression is sensitive to and modified by the background knowledge of the subject. We argue that such sensitivity is best explained as a difference in the visual experience of the facial expression, not just as a modification of the judgment based on this experience. The difference in experience is characterized as the result of the interference of background knowledge with the perceptual integration process for faces. Thus, according to the best explanation, we have to accept CP in some cases of emotion recognition. Finally, we discuss a recently proposed mechanism for CP in the face-based recognition of emotion. PMID- 26150797 TI - Comparing personal insight gains due to consideration of a recent dream and consideration of a recent event using the Ullman and Schredl dream group methods. AB - There have been reports and claims in the psychotherapeutic literature that the consideration of recent dreams can result in personal realizations and insight. There is theoretical support for these claims from work on rapid eye movement (REM) sleep having a function of the consolidation of emotional memories and the creative formation of connections between new and older memories. To investigate these claims, 11 participants (10 females, one male) reported and considered a recent home dream in a dream discussion group that following the "Appreciating dreams" method of Montague Ullman. The group ran 11 times, each participant attending and participating once. A further nine participants (seven females, two males) reported and considered a recent home dream in a group that followed the "Listening to the dreamer" method of Michael Schredl. The two studies each had a control condition where the participant also reported a recent event, the consideration of which followed the same technique as was followed for the dream report. Outcomes of the discussions were assessed by the participants on the Gains from Dream Interpretation (GDI) scale, and on its counterpart, the Gains from Event Interpretation scale. High ratings on the GDI experiential-insight subscale were reported for both methods, when applied to dreams, and for the Ullman method Exploration-Insight ratings for the dream condition were significantly higher than for the control event condition. In the Ullman method, self-assessment of personal insight due to consideration of dream content was also significantly higher than for the event consideration condition. The findings support the view that benefits can be obtained from the consideration of dream content, in terms of identifying the waking life sources of dream content, and because personal insight may also occur. To investigate the mechanisms for the findings, the studies should be repeated with REM and non-REM dream reports, hypothesizing greater insight from the former. PMID- 26150798 TI - The relationship between alcohol consumption, perceived stress, and CRHR1 genotype on the hypothalamic-pituitary-adrenal axis in rural African Americans. AB - OBJECTIVE: Rurally situated African Americans suffer from stress and drug-related health disparities. Unfortunately, research on potential mechanisms that underlie this public health problem have received limited focus in the scientific literature. This study investigated the effects of perceived stress, alcohol consumption, and genotype on the hypothalamic-pituitary-adrenal (HPA) Axis. METHODS: A rural sample of African American emerging adults (n = 84) completed a battery of assessments and provided six samples of salivary cortisol at wakeup, 30 min post wakeup, 90 min post wakeup, 3:00 PM, 3:30 PM, and 4:30 PM. RESULTS: Participants with a TT genotype of the CRHR1 (rs4792887) gene tended to produce the most basal cortisol throughout the day while participants with a CC genotype produced the least amount. Increased levels of perceived stress or alcohol consumption were associated with a blunted cortisol awakening response (CAR). Moreover, the CAR was obliterated for participants who reported both higher stress and alcohol consumption. CONCLUSION: Perceived stress and alcohol consumption had a deleterious effect on the HPA-Axis. Furthermore, genotype predicted level of cortisol production throughout the day. These findings support the need to further investigate the relationship between stress dysregulation, drug-use vulnerability, and associated health disparities that affect this community. PMID- 26150799 TI - The image of mind in the language of children with autism. PMID- 26150800 TI - Commentary "The sexualized-body-inversion hypothesis revisited: Valid indicator of sexual objectification or methodological artifact?". PMID- 26150801 TI - Effect Size as the Essential Statistic in Developing Methods for mTBI Diagnosis. AB - The descriptive statistic known as "effect size" measures the distinguishability of two sets of data. Distingishability is at the core of diagnosis. This article is intended to point out the importance of effect size in the development of effective diagnostics for mild traumatic brain injury and to point out the applicability of the effect size statistic in comparing diagnostic efficiency across the main proposed TBI diagnostic methods: psychological, physiological, biochemical, and radiologic. Comparing diagnostic approaches is difficult because different researcher in different fields have different approaches to measuring efficacy. Converting diverse measures to effect sizes, as is done in meta analysis, is a relatively easy way to make studies comparable. PMID- 26150802 TI - High rate copper and energy recovery in microbial fuel cells. AB - Bioelectrochemical systems (BESs) are a novel, promising technology for the recovery of metals. The prerequisite for upscaling from laboratory to industrial size is that high current and high power densities can be produced. In this study we report the recovery of copper from a copper sulfate stream (2 g L(-1) Cu(2+)) using a laboratory scale BES at high rate. To achieve this, we used a novel cell configuration to reduce the internal voltage losses of the system. At the anode, electroactive microorganisms produce electrons at the surface of an electrode, which generates a stable cell voltage of 485 mV when combined with a cathode where copper is reduced. In this system, a maximum current density of 23 A m(-2) in combination with a power density of 5.5 W m(-2) was produced. XRD analysis confirmed 99% purity in copper of copper deposited onto cathode surface. Analysis of voltage losses showed that at the highest current, most voltage losses occurred at the cathode, and membrane, while anode losses had the lowest contribution to the total voltage loss. These results encourage further development of BESs for bioelectrochemical metal recovery. PMID- 26150803 TI - Intra-ventral tegmental area HIV-1 Tat1-86 attenuates nicotine-mediated locomotor sensitization and alters mesocorticolimbic ERK and CREB signaling in rats. AB - Cigarette smoking prevalence in the HIV-positive individuals is profoundly higher than that in the HIV-negative individuals. We have demonstrated that HIV-1 transgenic rats exhibit attenuated nicotine-mediated locomotor activity, altered cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the mesocorticolimbic regions. This study investigated the role of HIV-1 transactivator of transcription (Tat) protein in the alterations of nicotine-mediated behavior and the signaling pathway observed in the HIV-1 transgenic rats. Rats received bilateral microinjection of recombinant Tat1-86 (25 MUg/side) or vehicle directed at ventral tegmental area (VTA) followed by locomotor testing in response to 13 daily intravenous injections of nicotine (0.05 mg/kg, freebase, once/day) or saline. Further, we examined the phosphorylated levels of CREB (pCREB) and ERK1/2 (pERK1/2) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and VTA. Tat diminished baseline activity in saline control rats, and attenuated nicotine-induced behavioral sensitization. Following repeated saline injection, the basal levels of pERK1 in the NAc and VTA and pERK2 in VTA were lower in the vehicle control group, relative to the Tat group. After repeated nicotine injection, pERK1 in NAc and VTA and pERK2 in VTA were increased in the vehicle group, but not in the Tat group. Moreover, repeated nicotine injections decreased pCREB in the PFC and VTA in the Tat group but not in the vehicle group. Thus, these findings indicate that the direct injection of Tat at the VTA may mediate CREB and ERK activity in response to nicotine-induced locomotor activity. PMID- 26150804 TI - High iron requirement for growth, photosynthesis, and low-light acclimation in the coastal cyanobacterium Synechococcus bacillaris. AB - Iron limits carbon fixation in much of the modern ocean due to the very low solubility of ferric iron in oxygenated ocean waters. We examined iron-limitation of growth rate under varying light intensities in the coastal cyanobacterium Synechococcus bacillaris, a descendent of the oxygenic phototrophs that evolved ca. 3 billion years ago when the ocean was reducing and iron was present at much higher concentrations as soluble Fe(II). Decreasing light intensity increased the cellular iron:carbon (Fe:C) ratio needed to support a given growth rate, indicating that iron and light may co-limit the growth of Synechococcus in the ocean, as shown previously for eukaryotic phytoplankton. The cellular Fe:C ratios needed to support a given growth rate were 5- to 8-fold higher than ratios for coastal eukaryotic algae growing under the same light conditions. The higher iron requirements for growth in the coastal cyanobacterium may be largely caused by the high demand for iron in photosynthesis, and to higher ratios of iron-rich photosystem I to iron-poor photosystem II in Synechococcus than in eukaryotic algae. This high iron requirement may also be vestigial and represent an adaptation to the much higher iron levels in the ancient reducing ocean. Due to the high cellular iron requirement for photosynthesis and growth, and for low light acclimation, Synechococcus may be excluded from many low-iron and low-light environments. Indeed, it decreases rapidly with depth within the ocean's deep chlorophyll maximum (DCM) where iron and light levels are low, and lower-iron requiring picoeukaryotes typically dominate the biomass of phytoplankton community within the mid to lower DCM. PMID- 26150806 TI - Proteome profiling of heat, oxidative, and salt stress responses in Thermococcus kodakarensis KOD1. AB - The thermophilic species, Thermococcus kodakarensis KOD1, a model microorganism for studying hyperthermophiles, has adapted to optimal growth under conditions of high temperature and salinity. However, the environmental conditions for the strain are not always stable, and this strain might face different stresses. In the present study, we compared the proteome response of T. kodakarensis to heat, oxidative, and salt stresses using two-dimensional electrophoresis, and protein spots were identified through MALDI-TOF/MS. Fifty-nine, forty-two, and twenty nine spots were induced under heat, oxidative, and salt stresses, respectively. Among the up-regulated proteins, four proteins (a hypothetical protein, pyridoxal biosynthesis lyase, peroxiredoxin, and protein disulphide oxidoreductase) were associated with all three stresses. Gene ontology analysis showed that these proteins were primarily involved metabolic and cellular processes. The KEGG pathway analysis suggested that the main metabolic pathways involving these enzymes were related to carbohydrate metabolism, secondary metabolite synthesis, and amino acid biosynthesis. These data might enhance our understanding of the functions and molecular mechanisms of thermophilic Archaea for survival and adaptation in extreme environments. PMID- 26150807 TI - Bottom-up modeling approach for the quantitative estimation of parameters in pathogen-host interactions. AB - Opportunistic fungal pathogens can cause bloodstream infection and severe sepsis upon entering the blood stream of the host. The early immune response in human blood comprises the elimination of pathogens by antimicrobial peptides and innate immune cells, such as neutrophils or monocytes. Mathematical modeling is a predictive method to examine these complex processes and to quantify the dynamics of pathogen-host interactions. Since model parameters are often not directly accessible from experiment, their estimation is required by calibrating model predictions with experimental data. Depending on the complexity of the mathematical model, parameter estimation can be associated with excessively high computational costs in terms of run time and memory. We apply a strategy for reliable parameter estimation where different modeling approaches with increasing complexity are used that build on one another. This bottom-up modeling approach is applied to an experimental human whole-blood infection assay for Candida albicans. Aiming for the quantification of the relative impact of different routes of the immune response against this human-pathogenic fungus, we start from a non-spatial state-based model (SBM), because this level of model complexity allows estimating a priori unknown transition rates between various system states by the global optimization method simulated annealing. Building on the non spatial SBM, an agent-based model (ABM) is implemented that incorporates the migration of interacting cells in three-dimensional space. The ABM takes advantage of estimated parameters from the non-spatial SBM, leading to a decreased dimensionality of the parameter space. This space can be scanned using a local optimization approach, i.e., least-squares error estimation based on an adaptive regular grid search, to predict cell migration parameters that are not accessible in experiment. In the future, spatio-temporal simulations of whole blood samples may enable timely stratification of sepsis patients by distinguishing hyper-inflammatory from paralytic phases in immune dysregulation. PMID- 26150808 TI - Proteomic profile response of Paracoccidioides lutzii to the antifungal argentilactone. AB - The dimorphic fungi Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis (PCM), a mycosis of high incidence in Brazil. The toxicity of drug treatment and the emergence of resistant organisms have led to research for new candidates for drugs. In this study, we demonstrate that the natural product argentilactone was not cytotoxic or genotoxic to MRC5 cells at the IC50 concentration to the fungus. We also verified the proteomic profile of Paracoccidioides lutzii after incubation with argentilactone using a label free quantitative proteome nanoUPLC-MS(E). The results of this study indicated that the fungus has a global metabolic adaptation in the presence of argentilactone. Enzymes of important pathways, such as glycolysis, the Krebs cycle and the glyoxylate cycle, were repressed, which drove the metabolism to the methylcytrate cycle and beta-oxidation. Proteins involved in cell rescue, defense and stress response were induced. In this study, alternative metabolic pathways adopted by the fungi were elucidated, helping to elucidate the course of action of the compound studied. PMID- 26150805 TI - Picornaviruses and nuclear functions: targeting a cellular compartment distinct from the replication site of a positive-strand RNA virus. AB - The compartmentalization of DNA replication and gene transcription in the nucleus and protein production in the cytoplasm is a defining feature of eukaryotic cells. The nucleus functions to maintain the integrity of the nuclear genome of the cell and to control gene expression based on intracellular and environmental signals received through the cytoplasm. The spatial separation of the major processes that lead to the expression of protein-coding genes establishes the necessity of a transport network to allow biomolecules to translocate between these two regions of the cell. The nucleocytoplasmic transport network is therefore essential for regulating normal cellular functioning. The Picornaviridae virus family is one of many viral families that disrupt the nucleocytoplasmic trafficking of cells to promote viral replication. Picornaviruses contain positive-sense, single-stranded RNA genomes and replicate in the cytoplasm of infected cells. As a result of the limited coding capacity of these viruses, cellular proteins are required by these intracellular parasites for both translation and genomic RNA replication. Being of messenger RNA polarity, a picornavirus genome can immediately be translated upon entering the cell cytoplasm. However, the replication of viral RNA requires the activity of RNA-binding proteins, many of which function in host gene expression, and are consequently localized to the nucleus. As a result, picornaviruses disrupt nucleocytoplasmic trafficking to exploit protein functions normally localized to a different cellular compartment from which they translate their genome to facilitate efficient replication. Furthermore, picornavirus proteins are also known to enter the nucleus of infected cells to limit host-cell transcription and down-regulate innate antiviral responses. The interactions of picornavirus proteins and host-cell nuclei are extensive, required for a productive infection, and are the focus of this review. PMID- 26150809 TI - Antimicrobial nisin acts against saliva derived multi-species biofilms without cytotoxicity to human oral cells. AB - OBJECTIVES: Nisin is a lantibiotic widely used for the preservation of food and beverages. Recently, investigators have reported that nisin may have clinical applications for treating bacterial infections. The aim of this study was to investigate the effects of ultra pure food grade Nisin ZP (>95% purity) on taxonomically diverse bacteria common to the human oral cavity and saliva derived multi-species oral biofilms, and to discern the toxicity of nisin against human cells relevant to the oral cavity. METHODS: The minimum inhibitory concentrations and minimum bactericidal concentrations of taxonomically distinct oral bacteria were determined using agar and broth dilution methods. To assess the effects of nisin on biofilms, two model systems were utilized: a static and a controlled flow microfluidic system. Biofilms were inoculated with pooled human saliva and fed filter-sterilized saliva for 20-22 h at 37 degrees C. Nisin effects on cellular apoptosis and proliferation were evaluated using acridine orange/ethidium bromide fluorescent nuclear staining and lactate dehydrogenase activity assays. RESULTS: Nisin inhibited planktonic growth of oral bacteria at low concentrations (2.5-50 MUg/ml). Nisin also retarded development of multi species biofilms at concentrations >=1 MUg/ml. Specifically, under biofilm model conditions, nisin interfered with biofilm development and reduced biofilm biomass and thickness in a dose-dependent manner. The treatment of pre-formed biofilms with nisin resulted in dose- and time-dependent disruption of the biofilm architecture along with decreased bacterial viability. Human cells relevant to the oral cavity were unaffected by the treatment of nisin at anti-biofilm concentrations and showed no signs of apoptotic changes unless treated with much higher concentrations (>200 MUg/ml). CONCLUSION: This work highlights the potential therapeutic value of high purity food grade nisin to inhibit the growth of oral bacteria and the development of biofilms relevant to oral diseases. PMID- 26150810 TI - Antimicrobial active herbal compounds against Acinetobacter baumannii and other pathogens. AB - Bacterial pathogens cause a number of lethal diseases. Opportunistic bacterial pathogens grouped into ESKAPE pathogens that are linked to the high degree of morbidity, mortality and increased costs as described by Infectious Disease Society of America. Acinetobacter baumannii is one of the ESKAPE pathogens which cause respiratory infection, pneumonia and urinary tract infections. The prevalence of this pathogen increases gradually in the clinical setup where it can grow on artificial surfaces, utilize ethanol as a carbon source and resists desiccation. Carbapenems, a beta-lactam, are the most commonly prescribed drugs against A. baumannii. The high level of acquired and intrinsic carbapenem resistance mechanisms acquired by these bacteria makes their eradication difficult. The pharmaceutical industry has no solution to this problem. Hence, it is an urgent requirement to find a suitable alternative to carbapenem, a commonly prescribed drug for Acinetobacter infection. In order to do this, here we have made an effort to review the active compounds of plants that have potent antibacterial activity against many bacteria including carbapenem resistant strain of A. baumannii. We have also briefly highlighted the separation and identification methods used for these active compounds. This review will help researchers involved in the screening of herbal active compounds that might act as a replacement for carbapenem. PMID- 26150811 TI - Hepatitis C virus and host cell nuclear transport machinery: a clandestine affair. AB - There is growing evidence that factors encoded by cytoplasmic replicating viruses functionally interact with components of the nucleocytoplasmic transport apparatus. They do so either to access the cell nucleus, thus affecting genes expression, or to interfere with nuclear transport functionality, hindering host immune response. Recent studies revealed that the hepatitis C virus (HCV) makes no exception, interacting with the host cell nuclear transport machinery at two different levels. On the one hand, small amounts of both core and NS5A localize within the host cell nucleus during productive infection, modulating gene expression and signaling functions to promote persistent infection. On the other hand, HCV infection causes a profound redistribution of certain nucleoproteins to the close proximity of endoplasmic reticulum membrane-derived viral replication factories, where viral RNA amplification occurs. These nucleoporins are believed to form nuclear pore complex-like structures, as suggested by their ability to recruit nuclear localization sequence-bearing proteins. Thus, both processes are linked to virus-induced persistence and pathogenesis, representing possible targets for the development of novel anti-HCV therapeutics. PMID- 26150812 TI - Zonation of bacterioplankton communities along aging upwelled water in the northern Benguela upwelling. AB - Upwelling areas are shaped by enhanced primary production in surface waters, accompanied by a well-investigated planktonic succession. Although bacteria play an important role in biogeochemical cycles of upwelling systems, little is known about bacterial community composition and its development during upwelling events. The aim of this study was to investigate the succession of bacterial assemblages in aging upwelled water of the Benguela upwelling from coastal to offshore sites. Water from the upper mixed layer at 12 stations was sampled along two transects from the origin of the upwelling to a distance of 220 km. 16S rRNA gene amplicon sequencing was then used in a bacterial diversity analysis and major bacterial taxa were quantified by catalyzed reporter deposition fluorescence in situ hybridization. Additionally, bacterial cell numbers and bacterial production were assessed. Community statistical analysis revealed a reproducible zonation along the two transects, with four clusters of significantly different microbial assemblages. Clustering was mainly driven by phytoplankton composition and abundance. Similar to the temporal succession that occurs during phytoplankton blooms in temperate coastal waters, operational taxonomic units (OTUs) affiliated with Bacteroidetes and Gammaproteobacteria were dominant during algal blooming whereas "Pelagibacterales" were highly abundant in regions with low algal abundance. The most dominant heterotrophic OTU (9% of all reads) was affiliated with "Pelagibacterales" and showed a strong negative correlation with phytoplankton. By contrast, the second most abundant heterotrophic OTU (6% of all reads) was affiliated with the phylum Verrucomicrobia and correlated positively with phytoplankton. Together with the close relation of bacterial production and phytoplankton abundance, our results showed that bacterial community dynamics is strongly driven by the development and composition of the phytoplankton community. PMID- 26150813 TI - Influence of Co and B 12 on the growth and nitrogen fixation of Trichodesmium. AB - We investigated the influence of varying cobalt (Co) and B12 concentrations to growth and nitrogen fixation of Trichodesmium, a major diazotroph in the tropical and subtropical oligotrophic ocean. Here we show that sufficient inorganic Co, 20 pmol L(-1), sustains the growth of Trichodesmium either with or without an additional B12 supply. We also found that in these culture conditions, nitrogen levels fixed by Trichodesmium were higher in treatments with insufficient B12 than in treatments with higher B12 availability. Under limited inorganic Co availability, ranging from 0.2 to 2 pmol L(-1), Trichodesmium growth was significantly compromised in cultures without B12. In these low Co concentrations, addition of 400 pmol L(-1) of B12 supported phytoplankton growth indicating that B12 supply augmented for the low Co concentrations. Our study demonstrates that Trichodesmium has an absolute Co requirement, which is not replaceable with Zn, and that B12 supply alleviates stress in cases where Co is limiting. These results show that the interlocking availabilities of Co and B12 may influence the growth and nitrogen fixation of Trichodesmium in the ocean. PMID- 26150814 TI - The regulatory function of LexA is temperature-dependent in the deep-sea bacterium Shewanella piezotolerans WP3. AB - The SOS response addresses DNA lesions and is conserved in the bacterial domain. The response is governed by the DNA binding protein LexA, which has been characterized in model microorganisms such as Escherichia coli. However, our understanding of its roles in deep-sea bacteria is limited. Here, the influence of LexA on the phenotype and gene transcription of Shewanella piezotolerans WP3 (WP3) was investigated by constructing a lexA deletion strain (WP3DeltalexA), which was compared with the wild-type strain. No growth defect was observed for WP3DeltalexA. A total of 481 and 108 genes were differentially expressed at 20 and 4 degrees C, respectively, as demonstrated by comparative whole genome microarray analysis. Furthermore, the swarming motility and dimethylsulfoxide reduction assay demonstrated that the function of LexA was related to temperature. The transcription of the lexA gene was up-regulated during cold acclimatization and after cold shock, indicating that the higher expression level of LexA at low temperatures may be responsible for its temperature-dependent functions. The deep-sea microorganism S. piezotolerans WP3 is the only bacterial species whose SOS regulator has been demonstrated to be significantly influenced by environmental temperatures to date. Our data support the hypothesis that SOS is a formidable strategy used by bacteria against various environmental stresses. PMID- 26150815 TI - Is lactate an undervalued functional component of fermented food products? AB - Although it has been traditionally regarded as an intermediate of carbon metabolism and major component of fermented dairy products contributing to organoleptic and antimicrobial properties of food, there is evidence gathered in recent years that lactate has bioactive properties that may be responsible of broader properties of functional foods. Lactate can regulate critical functions of several key players of the immune system such as macrophages and dendritic cells, being able to modulate inflammatory activation of epithelial cells as well. Intraluminal levels of lactate derived from fermentative metabolism of lactobacilli have been shown to modulate inflammatory environment in intestinal mucosa. The molecular mechanisms responsible to these functions, including histone deacetylase dependent-modulation of gene expression and signaling through G-protein coupled receptors have started to be described. Since lactate is a major fermentation product of several bacterial families with probiotic properties, we here propose that it may contribute to some of the properties attributed to these microorganisms and in a larger view, to the properties of food products fermented by lactic acid bacteria. PMID- 26150817 TI - Inflammation, Innate Immunity, and the Intestinal Stromal Cell Niche: Opportunities and Challenges. AB - Stromal cells of multiple tissues contribute to immune-mediated protective responses and, conversely, the pathological tissue changes associated with chronic inflammatory disease. However, unlike hematopoietic immune cells, tissue stromal cell populations remain poorly characterized with respect to specific surface marker expression, their ontogeny, self-renewal, and proliferative capacity within tissues and the extent to which they undergo phenotypic immunological changes during the course of an infectious or inflammatory insult. Extending our knowledge of the immunological features of stromal cells provides an exciting opportunity to further dissect the underlying biology of many important immune-mediated diseases, although several challenges remain in bringing the emerging field of stromal immunology to equivalence with the study of the hematopoietic immune cell compartment. This review highlights recent studies that have begun unraveling the complexity of tissue stromal cell function in immune responses, with a focus on the intestine, and proposes strategies for the development of the field to uncover the great potential for stromal immunology to contribute to our understanding of the fundamental pathophysiology of disease, and the opening of new therapeutic avenues in multiple chronic inflammatory conditions. PMID- 26150818 TI - The Spectrum and Clinical Significance of Autoantibodies in Rheumatoid Arthritis. PMID- 26150816 TI - Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm Blooded Vertebrates Through Comparative Transcriptomics. AB - Mononuclear phagocytes are organized in a complex system of ontogenetically and functionally distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic, and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections. We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover, we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey. PMID- 26150819 TI - Nano-Synthetic Devices in Leishmaniasis: A Bioinformatics Approach. AB - Synthetic biology is an investigative and constructive means of understanding the complexities of biology. Substantial progress in the fields has resulted in the creation of synthetic gene circuits, which when uploaded into the appropriate nanoliposomal vehicle, can be used for a tunable response in a cell. These tunable elements can be applied to treat diseased condition for a transition to a healthy state. Though in its nascent stage of development synthetic biology is beginning to use its constructs to bring engineering approaches into biomedicine for treatment of infectious disease leishmaniasis. PMID- 26150821 TI - Effect of ovary induction on bread wheat anther culture: ovary genotype and developmental stage, and candidate gene association. AB - Ovary pre-conditioned medium and ovary co-culture increased the efficiency of green doubled haploid plant production in bread wheat anther culture. The positive effect of this medium led to a 6- and 11-fold increase in the numbers of embryos and green plants, respectively, having a greater effect on a medium-low responding cultivar. Ovary genotype and developmental stage significantly affected microspore embryogenesis. By the use of Caramba ovaries it was possible to reach a 2-fold increase in the number of embryos and green plants, and to decrease the rate of albinism. Mature ovaries from flowers containing microspores at a late binucleate stage raised the number of embryos and green plants by 25 46% as compared to immature ovaries (excised from flowers with microspores at a mid-late uninucleate stage). The highest numbers of embryos and green plants were produced when using mature Caramba ovaries. Ovaries from Galeon, Tigre, and Kilopondio cultivars successfully induced microspore embryogenesis at the same rate as Caramba ovaries. Moreover, Tigre ovaries raised the percentage of spontaneous chromosome doubling up to 71%. Attempts were made to identify molecular mechanisms associated to the inductive effect of the ovaries on microspore embryogenesis. The genes TAA1b, FLA26, and WALI6 associated to wheat microspore embryogenesis, the CGL1 gene involved in glycan biosynthesis or degradation, and the FER gene involved in the ovary signaling process were expressed and/or induced at different rates during ovary culture. The expression pattern of FLA26 and FER could be related to the differences between genotypes and developmental stages in the inductive effect of the ovary. Our results open opportunities for new approaches to increase bread wheat doubled haploid production by anther culture, and to identify the functional components of the ovary inductive effect on microspore embryogenesis. PMID- 26150820 TI - Resistance to bio-insecticides or how to enhance their sustainability: a review. AB - After more than 70 years of chemical pesticide use, modern agriculture is increasingly using biological control products. Resistances to conventional insecticides are wide spread, while those to bio-insecticides have raised less attention, and resistance management is frequently neglected. However, a good knowledge of the limitations of a new technique often provides greater sustainability. In this review, we compile cases of resistance to widely used bio insecticides and describe the associated resistance mechanisms. This overview shows that all widely used bio-insecticides ultimately select resistant individuals. For example, at least 27 species of insects have been described as resistant to Bacillus thuringiensis toxins. The resistance mechanisms are at least as diverse as those that are involved in resistance to chemical insecticides, some of them being common to bio-insecticides and chemical insecticides. This analysis highlights the specific properties of bio insecticides that the scientific community should use to provide a better sustainability of these products. PMID- 26150822 TI - Correlation between differential drought tolerability of two contrasting drought responsive chickpea cultivars and differential expression of a subset of CaNAC genes under normal and dehydration conditions. AB - Drought causes detrimental effect to growth and productivity of many plants, including crops. NAC transcription factors have been reported to play important role in drought tolerance. In this study, we assessed the expression profiles of 19 dehydration-responsive CaNAC genes in roots and leaves of two contrasting drought-responsive chickpea varieties treated with water (control) and dehydration to examine the correlation between the differential expression levels of the CaNAC genes and the differential drought tolerability of these two cultivars. Results of real-time quantitative PCR indicated a positive relationship between the number of dehydration-inducible and -repressible CaNAC genes and drought tolerability. The higher drought-tolerant capacity of ILC482 cultivar vs. Hashem cultivar might be, at least partly, attributed to the higher number of dehydration-inducible and lower number of dehydration-repressible CaNAC genes identified in both root and leaf tissues of ILC482 than in those of Hashem. In addition, our comparative expression analysis of the selected CaNAC genes in roots and leaves of ILC482 and Hashem cultivars revealed different dehydration responsive expression patterns, indicating that CaNAC gene expression is tissue- and genotype-specific. Furthermore, the analysis suggested that the enhanced drought tolerance of ILC482 vs. Hashem might be associated with five genes, namely CaNAC02, 04, 05, 16, and 24. CaNAC16 could be a potential candidate gene, contributing to the better drought tolerance of ILC482 vs. Hashem as a positive regulator. Conversely, CaNAC02 could be a potential negative regulator, contributing to the differential drought tolerability of these two cultivars. Thus, our results have also provided a solid foundation for selection of promising tissue-specific and/or dehydration-responsive CaNAC candidates for detailed in planta functional analyses, leading to development of transgenic chickpea varieties with improved productivity under drought. PMID- 26150823 TI - Genome-wide identification of CAMTA gene family members in Medicago truncatula and their expression during root nodule symbiosis and hormone treatments. AB - Calmodulin-binding transcription activators (CAMTAs) are well-characterized calmodulin-binding transcription factors in the plant kingdom. Previous work shows that CAMTAs play important roles in various biological processes including disease resistance, herbivore attack response, and abiotic stress tolerance. However, studies that address the function of CAMTAs during the establishment of symbiosis between legumes and rhizobia are still lacking. This study undertook comprehensive identification and analysis of CAMTA genes using the latest updated M. truncatula genome. All the MtCAMTA genes were expressed in a tissues-specific manner and were responsive to environmental stress-related hormones. The expression profiling of MtCAMTA genes during the early phase of Sinorhizobium meliloti infection was also analyzed. Our data showed that the expression of most MtCAMTA genes was suppressed in roots by S. meliloti infection. The responsiveness of MtCAMTAs to S. meliloti infection indicated that they may function as calcium-regulated transcription factors in the early nodulation signaling pathway. In addition, bioinformatics analysis showed that CAMTA binding sites existed in the promoter regions of various early rhizobial infection response genes, suggesting possible MtCAMTAs-regulated downstream candidate genes during the early phase of S. meliloti infection. Taken together, these results provide basic information about MtCAMTAs in the model legume M. truncatula, and the involvement of MtCAMTAs in nodule organogenesis. This information furthers our understanding of MtCAMTA protein functions in M. truncatula and opens new avenues for continued research. PMID- 26150824 TI - An Arabidopsis neutral ceramidase mutant ncer1 accumulates hydroxyceramides and is sensitive to oxidative stress. AB - Ceramidases hydrolyze ceramide into sphingosine and fatty acids and, although ceramidases function as key regulators of sphingolipid homeostasis in mammals, their roles in plants remain largely unknown. Here, we characterized the Arabidopsis thaliana ceramidase AtNCER1, a homolog of human neutral ceramidase. AtNCER1 localizes predominantly on the endoplasmic reticulum. The ncer1 T-DNA insertion mutants had no visible phenotype, but accumulated hydroxyceramides, and showed increased sensitivity to oxidative stress induced by methyl viologen. Plants over-expressing AtNCER1 showed increased tolerance to oxidative stress. These data indicate that the Arabidopsis neutral ceramidase affects sphingolipid homeostasis and oxidative stress responses. PMID- 26150825 TI - It is time to classify biological aging as a disease. PMID- 26150826 TI - Why study moonlighting proteins? PMID- 26150827 TI - DNA/RNA transverse current sequencing: intrinsic structural noise from neighboring bases. AB - Nanopore DNA sequencing via transverse current has emerged as a promising candidate for third-generation sequencing technology. It produces long read lengths which could alleviate problems with assembly errors inherent in current technologies. However, the high error rates of nanopore sequencing have to be addressed. A very important source of the error is the intrinsic noise in the current arising from carrier dispersion along the chain of the molecule, i.e., from the influence of neighboring bases. In this work we perform calculations of the transverse current within an effective multi-orbital tight-binding model derived from first-principles calculations of the DNA/RNA molecules, to study the effect of this structural noise on the error rates in DNA/RNA sequencing via transverse current in nanopores. We demonstrate that a statistical technique, utilizing not only the currents through the nucleotides but also the correlations in the currents, can in principle reduce the error rate below any desired precision. PMID- 26150828 TI - Two different evolutionary lines of filamentous phages in Ralstonia solanacearum: their effects on bacterial virulence. AB - The integration and excision of various filamentous phage genomes into and out of their host chromosomes occurs by site-specific recombination. The mechanisms proposed for these events include reactions mediated by phage-encoded recombinases and host recombination systems. Site-specific integration of filamentous phages plays a vital role in a variety of biological functions of the host, such as phase variation of certain pathogenic bacterial virulence factors. The importance of these filamentous phages in bacterial evolution is rapidly increasing with the discovery of new phages that are involved in pathogenicity. Studies of the diversity of two different filamentous phages infecting the phytopathogen Ralstonia solanacearum provide us with novel insights into the dynamics of phage genomes, biological roles of prophages, and the regulation and importance of phage-host interactions. PMID- 26150829 TI - Using linkage maps to correct and scaffold de novo genome assemblies: methods, challenges, and computational tools. AB - Modern high-throughput DNA sequencing has made it possible to inexpensively produce genome sequences, but in practice many of these draft genomes are fragmented and incomplete. Genetic linkage maps based on recombination rates between physical markers have been used in biology for over 100 years and a linkage map, when paired with a de novo sequencing project, can resolve mis assemblies and anchor chromosome-scale sequences. Here, I summarize the methodology behind integrating de novo assemblies and genetic linkage maps, outline the current challenges, review the available software tools, and discuss new mapping technologies. PMID- 26150830 TI - Genomic basis of evolutionary change: evolving immunity. AB - Complex traits are manifestations of intricate gene interaction networks. Evolution of complex traits revolves around the genetic variation in such networks. Genomics has increased our ability to investigate the complex gene interaction networks, and characterize the extent of genetic variation in these networks. Immunity is a complex trait, for which the ecological drivers and molecular networks are fairly well understood in Drosophila. By characterizing the natural variation in immunity, and mapping how the genome changes during the evolution of immunity in Drosophila, we can integrate our knowledge on the complex genetic architecture of traits and the molecular basis of evolutionary processes. PMID- 26150831 TI - Cervical cancer screening and HPV genotype distribution among asymptomatic patients of Karachi Pakistan. AB - BACKGROUND: Cervical cancer is the second most prevalent cancer in females worldwide. Human papillomavirus (HPV) infection is a sexually transmitted infection. However, in addition to HPV infection, other factors exist that influence the risk of developing cervical cancer. In Pakistan most women who developed cervical cancer have been infrequently or never screened. OBJECTIVE: To determine the prevalence of HPV infection and its subtype profile among asymptomatic patients with pre cancerous cervical intraepithelial lesion. METHODS: In this hospital-based descriptive study, 160 asymptomatic females attending gynecology clinics were subjected to HPV screening after obtaining informed consent. Cervical Scrapings were examined by cytopathology and colposcopic directed biopsies taken. High-grade intraepithelial lesion (HSIL) CIN 2, and Low-grade intraepithelial lesion (LSIL) CIN-1 were selected. Samples were analyzed for the presence of HPV-DNA general and type specific genotype 16 and 18. HPV- DNA was extracted by QIA amp DNA kit protocol and amplification was done by polymerase chain reaction (PCR) and genotyped by type specific primers. RESULTS: Out of 160, 17 Pap smear tests were positive, 6 (35.3%) with abnormal results (HSIL) CIN-2 were HPV-DNA positive. Among them, 5 (83.3%) had subtype 16 and in 1 (16.7%) case the genotype was undetectable. The remaining 11(6.9%) with pre cancer minimal abnormal (LSIL) CIN-1 presented. Out of them 3 (27.3%) were HPV-DNA positive with subtype 16. Five (45.4%) were followed by repeated pap smear every six months for two years, and the rest of 3 (27.3%) patients refused for the test. CONCLUSION: A high incidence of Human papillomavirus (HPV) infection is found in women with pre cancerous lesion of cervix in Pakistani women. PMID- 26150832 TI - Undergraduate Medical Education Research in Malaysia: Time for a Change. AB - OBJECTIVE: Special Study Module (SSM) is a mandatory research module implemented in Universiti Kebangsaan Malaysia (UKM). The objective of this paper is to provide a brief overview on the student research activities and to find out the outcome measures in terms of publication. METHODS: It was a retrospective study done on SSM research projects at UKM. The SSM research is conducted from beginning of year-4 until 1(st) seven weeks of year-5. In year-4, students are assigned to a faculty-supervisor in small groups and spend every Thursday afternoon to plan and carry the research. Whole first seven weeks of year-5, students are placed with their supervisor continuously to collect data, do analysis, write report and present in the scientific conference. Outcomes of 5 years SSM research-projects starting from 2008/2009 to 2012/2013 academic session were analyzed. RESULTS: Total 257 projects were completed and presented in annual scientific meetings from which 57 (22.2%) articles were published in peer reviewed journals. CONCLUSION: Mandatory undergraduate student research project brings an opportunity to develop students' capacity building from conception to final report writing and thereby narrowing the gap between education and practice. Medical schools should implement research module to bring changes in research and publication culture of undergraduate medical education. PMID- 26150833 TI - Stress-coping strategies among medical residents in Saudi Arabia: A cross sectional national study. AB - OBJECTIVES: Maladaptive stress-coping strategies have been linked to reduced quality of life, psychiatric disorders, and reduced work performance among residents or physicians. This study aimed to examine stress-coping strategies among medical residents in Saudi Arabia and their association with stress levels and important personal characteristics. METHODS: This cross-sectional study was conducted between May and October 2012. Residents of different specialties were recruited from a national database. Stress-coping strategies were assessed using the 28-item brief coping scale (BCS), while stress was assessed using the perceived stress scale (PSS). RESULTS: Nine hundred seventeen residents completed both BCS and PSS assessments. Almost 55% of participants were males, 88% were Saudi, 58% were married, and 15% had positive history of psychiatric disorders. The adaptive stress-coping strategy with the highest score was religion, followed by planning, acceptance, and active coping. The maladaptive stress-coping strategy with the highest score was self-blame, followed by self-distraction, and venting. Maladaptive stress-coping strategies were associated with high stress level, female gender, and history of psychiatric disorders. Stress-coping strategies were not correlated/associated with age, presence of major medical illnesses, or stress management education/training. CONCLUSION: Adaptive stress coping strategies were more frequently used among a sample of residents in Saudi Arabia than maladaptive stress-coping strategies, with higher use of religion in coping than previously reported. To avoid potential negative impact on resident well-being, future studies among residents should aim to identify the type of stress management program that most positively impacts stress-coping skills. PMID- 26150834 TI - Efficacy and safety of Pro Re Nata regimen without loading dose ranibizumab injections in retinal vein occlusion. AB - OBJECTIVES: To evaluate the effects and safety of intravitreal ranibizumab on visual acuity and anatomic results in the treatment of macular edema due to retinal vein occlusion (RVO). METHODS: Forty Six eyes of 45 patients who were administered intravitreal ranibizumab because of macular edema due to Retinal Vein Occlusion (RVO) were included in this retrospective clinical study. During monthly follow-up, the best corrected visual acuity values in terms of LogMAR with The Early Treatment Diabetic Retinopathy Study (ETDRS) chart, central macular thickness (CMT), and complications were examined. Cases were classified as central retinal vein occlusion (CRVO), superotemporal branch retinal vein occlusion (BRVO), and inferotemporal BRVO. We only included RVO patients but using ETDRS chart for the vision measurement. RESULTS: In all follow-up months, there was a significant increase in BCVA in all RVO cases and in superotemporal BRVO cases after the first injection of ranibizumab. Although there was no significant increase in the 1(st) month of follow-up period compared to pre treatment, there was significant increase in 2-6 months in inferotemporal BRVO patients. There was no statistically significant increase in 1(st) and 2(nd) month follow-up periods compared to pre-treatment; however there was a significant increase in 3-6 months in the CRVO patients. There was a significant decrease in average CMT measurements in all follow-up months compared to pre treatment in all RVO cases, in superotemporal and inferotemporal BRVO cases. There was no significant decrease in average CMT measurements in the 1(st), 2nd, and 3(rd) months compared to pre-treatment although there was a significant decrease in 4-6 months in cases included in the CRVO patients. CONCLUSIONS: Intraocular ranibizumab injections provided rapid, effective treatment for macular edema due to RVO with low rates of ocular and nonocular safety events. However, repeated injections and frequent follow-up intervals may be required. PMID- 26150835 TI - Predictive value of brachial-ankle artery pulse wave velocity to heart failure with preserved ejection fraction in hospitalised patients with acute dyspnoea. AB - OBJECTIVE: To explore the predictive value of the brachial-ankle artery pulse wave velocity (baPWV) for heart failure with preserved ejection fraction (HFpEF). METHODS: Echocardiographic data, B-type natriuretic peptide (BNP) level, and baPWV were assessed in 111 consecutive patients admitted for acute dyspnea. The patients were divided into the HFpEF group (n=71) and the control group (n=40). RESULTS: Multivariate logistic regression analyses revealed that the ratio of the early mitral inflow velocity to the tissue Doppler velocity (E/e') at the lateral mitral annulus, BNP, and baPWV were independently predictive of HFpEF. Adding the baPWV to E/e' at the lateral annulus and to the BNP resulted in an increase in the area under the curve (AUC) to 0.855 (vs. lateral E/e' alone, P=0.02) or 0.880 (vs. BNP alone, P=0.02), respectively. The AUC of the three combining indicators including the lateral E/e', BNP, and baPWV was 0.910 (vs. E/e' lateral alone, P<0.001; vs. BNP alone, P=0.001). The diagnostic accuracy was improved significantly after adding the baPWV to the diagnostic criteria of the 2007 ESC consensus statement (net reclassification improvement 0.127, P=0.02). CONCLUSIONS: Adding the baPWV to the current diagnostic indicators of the 2007 ESC consensus statement could increase the accuracy of predicting HFpEF. PMID- 26150836 TI - Morbidity and impact on quality of life in patients with indwelling ureteral stents: A 10-year clinical experience. AB - OBJECTIVE: Prospective analysis of the prevalence of symptoms, tolerability and complications associated with ureteral stents and their impact on quality of life based on the Flanagan Quality of Life Scale and a not-validated questionnaire from our clinic. METHODS: A total of 2200 adult patient participated to this study in a period of 10 years (2003-2012). Those patients were asked to complete the QOLS and a not-validated questionnaire from our clinic, before ureteral indwelling, 7 day after ureteral indwelling and 14 days after removal of the stent. RESULTS: Total 1520 patient aged between 18 and 84 years completed the study. The analysis of data showed that the unpleasant symptoms caused by stent were encountered more frequently at 7 days after stent insertion, in terms of urinary frequency, dysuria, urgency and macroscopic haematuria, this difference being statistically significant (p<0.05). After analysis the responses to QOLS questionnaire, at 7 days after stent placement, mean scores show a clear reduction in the QoL of those patients, in all cases the standard deviation being at a great value, indicating a high variability of responses, but at 14 days after its suppression of stent the average scores are somewhat closer to the baseline. CONCLUSIONS: Our study brings many elements that shows a statistically significant increase in the incidence of numerous side effects and impaired quality of life. It contributes to existing data from the literature as regards the knowledge of the pathology determined by the presence of foreign body in the urinary tract and in providing patient counseling. PMID- 26150837 TI - Validity of C-reactive protein (CRP) for diagnosis of neonatal sepsis. AB - OBJECTIVE: To determine the validity of C-reactive protein levels for diagnosis of neonatal sepsis. METHODS: A cross sectional (Validation) study was conducted at Neonatology unit in KRL general hospital (emergency/OPD) of 7 months duration from February 2012 to August 2012. By using purposive sampling technique, 147, sample size was calculated by using WHO sample size calculator taking sensitivity 75%, specificity 95%, expected prevalence 50%, desired precision 10% and confidence level 95%. RESULTS: Mean age of the neonates was 5.72 days + 3.86. Male patients were 81(55.1%) while 66(44.9%) were female. Neonatal sepsis was observed in 43(29.25%) and were confirmed through blood culture while 104(70.75%) were not confirmed on blood culture as neonatal sepsis. The sensitivity and specificity of CRP in diagnosis of acute neonatal sepsis was 76.92% and 53.49% respectively while it had a positive predictive value of 80% and negative predictive value of 48.94%. Over all the diagnostic accuracy of CRP in diagnosis of neonatal sepsis was 70.07%. CONCLUSION: CRP estimation does have a role in the diagnosis of neonatal sepsis but the test is not specific enough to be relied upon as the only indicator. PMID- 26150838 TI - Factors determining poor prognostic outcomes following diabetic hand infections. AB - BACKGROUND AND OBJECTIVE: Hand ulcers are seen in a small percentage of patients with diabetes. The predisposing factors of diabetic hand varies between different countries. However, the effects of predisposing factors on prognosis are not clear in diabetic hand infections. In this study, our aim was to determine the effects of predisposing factors on poor prognostic outcomes in patients with diabetes mellitus. METHODS: Thirty-four patients with diabetes mellitus who were treated and followed up for a hand infection in between 2008 and 2014 were investigated retrospectively. Patients were evaluated according to predisposing factors defined in the literature that included disease period, age, gender, admission time, presence of neuropathy, smoking habits, HbA1c levels at admission time, peripheral vascular disease, end-stage renal disease (ESRD), and trauma. Death and minor/major amputation cases during treatment were defined as poor prognosis. RESULTS: Patients who had ESRD, peripheral neuropathy, or an HbA1c level greater than 10% had significantly higher amputation rates. CONCLUSIONS: Peripheral neuropathy, ESRD, and HbA1c levels greater than 10% at the time of admission were determined as poor prognosis criteria for diabetic hand treatment. PMID- 26150839 TI - Vascular endothelial function of patients with stable coronary artery disease. AB - OBJECTIVES: To evaluate vascular endothelial function and contributing factors in coronary heart disease (CHD) patients. METHODS: One hundred twenty six CHD outpatients were randomly recruited. Reactive hyperemia index (RHI) <1.67 indicates endothelial dysfunction. Correlation between RHI and different biochemical parameters was evaluated. RESULTS: RHI in patients receiving statins treatment was significantly higher than patients without statins treatment (P<0.05). RHI in patients with more than 3 risk factors for CHD was also markedly lower than that in patients with <=2 risk factors (P<0.05). Patients with lesions at several branches of coronary artery had a markedly lower RHI when compared with those with coronary lesions at a single branch (P<0.05). For patients without statins treatment, RHI increased significantly after statins treatment for 1 month (P=0.01). In patients with endothelial dysfunction, FBG, HbA1C, hs CRP and Hcy were significantly higher than those in patients with normal endothelial function (P<0.05 for all). Smokers with CHD had a remarkably lower RHI when compared with non-smokers (P<0.05). CONCLUSIONS: Smoking, FBG, HbA1C, Hcy and hs-CRP are significantly associated with endothelial dysfunction. Endothelial dysfunction is also related to the numbers of risk factors for CHD, degree of coronary lesions and statins. Statins treatment may significantly improve the endothelial function of CHD patients. PMID- 26150840 TI - The job satisfaction and burnout levels of primary care health workers in the province of Malatya in Turkey. AB - OBJECTIVE: The objective was to determine the job satisfaction and burnout levels of primary care health workers in Malatya in Turkey. METHODS: The sample of the study included 186 physicians, 126 midwives and 106 nurses working in primary health care. The Minnesota Job Satisfaction Scale and the Maslach Burnout Scale were used in the study. RESULTS: The general, internal and external job satisfaction score medians of the study group were 3.35, 3.50 and 3.12 respectively, while the median of the Maslach Personal accomplishment score was 23.00, the Emotional Burnout score median was 15.00, and the Depersonalisation score median was found to be 3.00. CONCLUSIONS: The manner of their employment in the departments where they work, their perception of their economic circumstances and their satisfaction of the department where they work have an impact on the job satisfaction and burnout levels of workers. PMID- 26150841 TI - Mycoplasma pneumonia infection and asthma: A clinical study. AB - OBJECTIVES: To evaluate the correlation between mycoplasma pneumonia infection and the severity of asthma as well as asthma control, to help physicians in respiratory department better make treatment strategies. METHODS: Since January 2012 to May 2014, we consecutively recruited 149 out-patients diagnosed with asthma in acute or convalescent phase from the department of respiratory medicine of our hospital. The pulmonary function tests, sputum induction examination, measurement of IgM, IgG and IgE in serum, evaluation of asthma control were carried out for all the included patients. RESULTS: In 78 cases with asthma in acute phase, mycoplasma pneumonia infection was confirmed in 38 cases (48.71%), and in 71 cases in stable state, mycoplasma pneumonia infection was confirmed in 22 cases (30.98%). There was significant difference in the rate of mycoplasma pneumonia infection between the two groups (p<0.05). The FEV1% Pred and ACT scores were significantly lower in mycoplasma pneumonia infection cases than those in no mycoplasma pneumonia infection cases (p<0.05), while the eosinophil count and IgE in serum were significantly higher in mycoplasma pneumonia infection cases (p<0.05). CONCLUSIONS: Mycoplasma pneumonia infection may play more important role in the occurrence of acute asthma, and it can lead to decreased pulmonary function, difficulty in controlling asthma and more severe airway inflammation. PMID- 26150842 TI - Surgical management of axillosubclavian vascular injuries. AB - OBJECTIVE: Complex surgical exposures to upper extremity injuries required for conventional surgery correlate with a high morbidity and mortality. We present our results with conventional surgery following injuries of the subclavian and axillary vessels. METHODS: Between November 2007 and March 2012, 29 cases with subclavian-axillary vascular injury were operated. Diagnostic and treatment methods, associated organ injury, morbidity and mortality rates in these cases were respectively reviewed. RESULTS: The causes of injuries were stab wounds in 11 cases (37.9%), gunshot wounds in 9 cases (31%), iatrogenic injuries in 5 cases (17.2%) and blunt trauma 4 cases (13.7%). Eight patients (27.5%) had isolated arterial injury while 21 patients (72.4%) had coexisting organ injury (vein, bone, soft tissue, nerve). Primary repair and usage of saphenous vein were the most common surgical methods. One patient died due to myocardial infarction. (Mortality 3.4%). CONCLUSIONS: Vascular injuries of axillosubclavian are frequently associated with neurogenic, osseous and soft tissue injuries and should have early intervention. Conventional surgery remains the choice of treatment in patients with poor status and urgency. PMID- 26150843 TI - Bone mineral density in university aged Saudi females. AB - OBJECTIVE: The aim of the study was to investigate bone mineral density (BMD) in young Saudi females (20-25 years) using Dual-energy x-ray absorptiometry (DXA), as it is a widely utilized modality for the measurement of BMD, used for the diagnosis of osteoporosis and osteopenia. METHODS: BMD measurements were performed in the spine and the neck of the femur in 101 young females. RESULTS: 37% and 34% patients had osteopenia in the spine and the neck of the femur respectively, BMD values = 0.98 and 0.81 gm/cm(2) respectively). Whereas 5% had osteoporosis in the spine area, BMD values = 0.82 gm/cm(2)). Of the 101 subjects, 53 (52.5%) young females did not suffer from osteopenia in either both site, whereas 23 (22.7%) females had osteopenia in both sites, the remaining 25 subjects (25% of the subject included) had either osteopenia or osteoporosis in one of the sites. A strong association between BMD values with weight was found. CONCLUSIONS: We found that one third of the young Saudi females sampled suffer from osteopenia. Additionally, body weight has a positive relationship with bone mineral density. PMID- 26150844 TI - Imipenem Resistant Pseudomonas aeruginosa: The fall of the final quarterback. AB - OBJECTIVE: To isolate, determine the frequency, and study the demographic trends of MBL positive Pseudomonas aeruginosa from imipenem resistant isolates collected from clinical samples in a tertiary care hospital of Pakistan. METHODS: In this cross sectional study a total of 230 strains of Pseudomonas were isolated from various clinical specimens on the basis of culture and biochemical tests. Imipenem resistant isolates were selected by Kirby Bauer Diffusion technique, followed by screening for MBL production by Imipenem EDTA Combined Disk Test. Demographic details of each patient were recorded on a separate questionnaire. Chi-Square goodness-of-fit test was computed to review the isolation of MBL positive isolates (P-value <= 0.05) in different specimen. RESULTS: Out of 230 strains of P. aeruginosa 49.5% were imipenem resistant; MBL production was confirmed in 64.9% of the resistant isolates. Resistance to polymyxin B (12.5%) was notable. Majority of the MBL positive strains were isolated from patients aged between 20-39 years (45.9%) and the predominant source was pus (43.24%) which was found to be statistically significant (P-value=0.04). Outpatient departments (24.3%) and burn unit (21.6%) were the major places for resistant isolates. CONCLUSION: MBL production is one of the major causes of IRPA. Increasing resistance to polymyxin B is grave. Due to acquisition of MBL strains MDR P. aeruginosa has become endemic in tertiary setups. PMID- 26150845 TI - Do Hypertension, diabetes mellitus and obesity increase the risk of severity of nephrolithiasis? AB - OBJECTIVE: In this study we planned to investigate the relationship between presence of kidney stones and stone burden with hypertension (HT), diabetes mellitus (DM) and body mass index (BMI). METHODS: A total of 574 patients were included in the study. None of the patients had a history of stones. The 121 patients with kidney stone identified on ultrasound evaluation and the 453 patients with no stones were compared in terms of HT, BMI and DM. The stone burden of 121 patients with diagnosed stones was compared in terms of the same variables. RESULTS: Of the 121 patients with kidney stones 30 (24.7%) had HT, while 66 (14.5%) of the 453 patients without stones had HT (p=0.007). BMI values of those with and without stones were 27.2 +/- 4.93 kg/m(2) and 25.29 +/- 4.12 kg/m(2), respectively (p<0.001). Twenty-five (20.6%) of the patients with stones diagnosed by ultrasound had DM, while 49 (10.8%) of those without stones had DM (p=0.004). When comparing patients with and without kidney stones, logistic regression analysis revealed that DM (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.17 to 3.63, p=0.013) and BMI (OR 1.08, CI 1.03 to 1.13, p=0.003) were independently associated with presence of stones. No significant relationship was found between the same variables and cumulative stone diameter (CSD) and stone surface area (SA) evaluated for stone burden. CONCLUSIONS: While diabetes mellitus, Hypertension and increased Body Mass Index may add to the possibility of stone formation, they did not affect stone burden. PMID- 26150846 TI - Therapeutic effects of laparotomy and laparoscopic surgery on patients with gastric cancer. AB - OBJECTIVE: To compare the therapeutic effects of laparotomy and laparoscopic surgery on patients with gastric cancer. METHODS: Sixty-six patients with gastric cancer who were treated in our hospital from January 2012 to December 2013 were selected and divided into a control group and an observation group by the random number method (n=33). The control group was treated by traditional laparotomy, and the observation group was treated by laparoscopic surgery. CD4/CD8 ratios and IgG expressions in the patients were detected on preoperative and postoperative fourth days. Intraoperative blood loss, surgical time, time of anal gas evacuation and time of postoperative independent ambulation of the two groups were observed. RESULTS: The intraoperative blood loss, surgical time, time of anal gas evacuation, time of postoperative independent ambulation, time of urinary catheter indwelling and average hospitalization stay length of the observation group were significantly different from those of the control group (P<0.05). The postoperative rates of fever and complications in the observation group were significantly lower than those of the control group, and the two groups had significantly different CD4/CD8 ratios and IgG levels on the postoperative 4th day (P<0.05). CONCLUSION: Compared with traditional laparotomy, laparoscopic surgery can well treat patients with gastric cancer minimally invasively. Meanwhile, their postoperative recovery was facilitated due to slightly affected humoral immunity and cellular immune function. PMID- 26150847 TI - Simple clinical risk score for no-reflow prediction in patients undergoing primary Percutaneous Coronary Intervention with acute STEMI. AB - OBJECTIVES: To identify the STEMI patients at high risk in terms of no-reflow during percutaneous coronary intervention (PCI) with a simple risk score system that can be used before reperfusion. METHODS: Total 173 patients who had undergone primary or rescue percutaneous coronary intervention following the diagnosis of STEMI, were classified as "no-reflow" developers and "no-reflow" non developers, during the procedure. The pre-procedural ECGs, laboratory parameters, demographic data, time for the treatment, and the treatment methods were evaluated with univariate analysis. The independent predictors were identified by multivariate logistic regression analysis among the no-reflow risk factors. Using the independent predictors, we developed a simple risk score system proportional to area under the ROC (AUROC) curves. RESULTS: The independent predictors of "no reflow" phenomenon were identified as follows: high values of blood glucose at reference; long symptom-onset-to-balloon-time; and low lymphocyte count. The incidence rates of "no-reflow" in patients with low (0-1), moderate (2-3) and high (4-6) risk factors were 13.3%, 40.0%, and 46.7%, respectively. The risk score system demonstrated a good risk prediction between patients with various risk levels of the development of "no-reflow" with a c-statistics of 0.734 (95% CI 0.654-0.814). CONCLUSION: The development of "no-reflow" which is an adverse event in STEMI treatment can be predicted efficiently by simple clinical risk scoring method. PMID- 26150848 TI - Vaginitis in pregnancy is related to adverse perinatal outcome. AB - OBJECTIVE: To determine whether education level and occupation are risk factors of vaginitis in pregnant women and to investigate relationship between vaginitis occurrence during pregnancy and perinatal mortality rates. METHODS: A total of 319 women of early pregnancy or mid-pregnancy were enrolled. Six specimens were collected from posterior fornix of each pregnant woman and then cultured for identification of Neisseria gonorrhoeae, intestinal bacteria, general bacteria, fungi, mycoplasma, and chlamydia, respectively. RESULTS: The pregnant women in the "elementary school or below" group and the "middle school" group had significantly higher incidences of vaginitis compared with the pregnant women in the groups of "high school", "skill education", and "college or above". The pregnant women in the groups of "Worker", "Government employee", "Company employee", and "Professionals" had significantly lower vaginitis incidences. The women with infections of Neisseria gonorrhoeae, intestinal bacteria, and general bacteria had higher perinatal mortalities (0.063 +/- 0.011, 0.052 +/- 0.012, and 0.017 +/- 0.008, respectively) than women with infections of fungi, mycoplasma, and Chlamydia (0.002 +/- 0.007, 0.003 +/- 0.004, and 0.001 +/- 0.001, respectively). CONCLUSIONS: Education level and occupation are risk factors related to incidences of vaginitis in pregnant women. The bacteria-related vaginitis is a major reason of perinatal mortality. PMID- 26150849 TI - Evaluation of dry eye findings in patients with vitiligo. AB - OBJECTIVE: To evaluate the association of dry eye and vitiligo diseases with objective parameters and a questionnaire. METHODS: The study was conducted in 30 vitiligo patients and 31 patients with non-complicated refractory complaints. All the patients underwent complete ophthalmologic examinations including fluorescein break-up time (FBU), corneal fluorescein staining (CFS) and Schirmer test-I. The dry eye status was evaluated by means of Ocular Surface Disease Index (OSDI). RESULTS: The groups were similar regarding the age and gender distribution. The vitiligo group had higher OSDI scores (26.1+/-15.9 vs 14.7+/-5.4, t-test, p<0.001), shorter FBU (7.8+/-2.9 vs 9.8+/-2.2, Mann Whitney U test, p=0.005) and higher CFS positivity (18/30 vs 3/31, chi-square test, p<0.001) than control group. The groups were similar regarding the Meibomian Gland Dysfunction (MGD) and Schirmer test results. Fourteen (46.7%) of vitiligo patients had periocular involvement. The analysis within vitiligo patients revealed that FBU and Schirmer test were shorter in patients with periocular involvement, the OSDI scores and MGD status were similar. CONCLUSION: Our study suggest a possible association of dry eye and vitiligo diseases. The diagnostic tools for dry eye disease are in good correlation with each other. The OSDI questionnaire seems practical for both diagnostic purposes and follow-up. PMID- 26150850 TI - Low dose albumin for the prevention of renal impairment following large volume paracentesis in cirrhosis. AB - OBJECTIVES: To evaluate the effect of low dose Albumin i.e. 4 grams per litre of ascitic fluid after large volume paracentesis (LVP) for the prevention of paracentesis induced circulatory dysfunction (PICD) related renal impairment in cirrhosis. METHODS: Case records of all patients with cirrhosis who underwent LVP from January 12(th), 2011 till December 29(th), 2013 were reviewed. Patients were excluded if they had spontaneous bacterial peritonitis, creatinine >1.5 mg/dl, hepatoma or if volume of ascitic fluid removed was <5 litres. Data including age, gender, cause of cirrhosis, CTP score and volume of ascitic fluid drained were noted. In addition serum creatinine and serum sodium at baseline and one week post paracentesis were recorded. RESULTS: Two hundred and fourteen patients with cirrhosis underwent LVP during the study period. One hundred and thirty nine patients met the inclusion criteria and were analyzed. Patients were divided into two groups based on the amount of albumin given. The amount of albumin given was 25 grams and 50 grams while the volume of ascitic fluid removed were 6.2+/-1 litres and 10.4+/-1.5 litres in groups A and B respectively. One hundred and eight patients were in group A while thirty one patients were in group B respectively. Both groups received albumin at a dose of 4 grams per litre of ascitic fluid removed. Mean age in both groups were 53 years. Hepatitis C was the commonest etiology in both the groups, followed by Hepatitis B. More than 70% patients in both the groups were in child class C. Serum creatinine at baseline and one week post LVP was 1.04+/-0.24 mg/dl and 1.07+/-0.35 mg/dl in GROUP A while 1.11+/-0.23 mg/dl and 1.41+/-0.94 mg/dl in GROUP B. (P value 0.35). Similarly, serum sodium at baseline and one week post LVP was 130 +/-5.6 meq/lit and 129.6+/-5.9 meq/lit in GROUP A while 127.6+/-5.8 meq/lit and 128+/-6.2 meq/lit in GROUP B respectively. (P value 0.14). CONCLUSION: This study suggests that 4 grams of albumin per litre of ascitic fluid drained is effective in preventing the PICD related renal impairment following large volume paracentesis in cirrhosis. PMID- 26150851 TI - Determination of the patient safety culture among nurses working at intensive care units. AB - OBJECTIVE: To determine the patient safety culture among nurses working at intensive care units. METHODS: This descriptive study was conducted at intensive care units of Health Practice and Research Center of Erciyes University and Kayseri Education and Research Hospital in the city center of Kayseri in Turkey. Three hundred sixteen nurses working at intensive care units at these hospitals were included in the study. Data were collected by using Hospital Survey on Patient Safety Culture (HSOPSC), developed by Agency for Healthcare Research and Quality. Percentage distribution and Mann Whitney U Test were used to analyze the data. RESULTS: About 13.6% of the nurses working at intensive care units stated that they faced incidents of potential threat to the patient safety and that 48.8% of these cases were falls. Although a great majority of the nurses (88%) indicated that they never documented a case report, they assessed the patient safety in their institution as acceptable (43%). Out of the 12 dimensions of Hospital Survey on Patient Safety Culture, the percentage of positive responses was the highest for "teamwork within units" dimension and lowest for the "non punitive response to error" dimension. CONCLUSION: Awareness of the nurses regarding patient safety should be raised and their related knowledge should be kept up-to-date through more frequent in-service trainings. PMID- 26150852 TI - Declined plasma sfrp5 concentration in patients with type 2 diabetes and latent autoimmune diabetes in adults. AB - OBJECTIVE: Secreted frizzled-related protein 5 (sfrp5), like adiponectin, has been identified as a novel insulin-sensitising and anti-inflammatory adipokine. Our objective was to determine whether differences of circulating plasma sfrp5 concentration exist among type 2 diabetes (T2D), latent autoimmune diabetes in adults (LADA) and healthy population. METHODS: Enzyme-linked immuno sorbent assay was employed to detect the circulating sfrp5 level in plasma, and other lab tests such as fasting glucose and creatinine were also examined. Correlation analysis between sfrp5 and characteristics of subjects was conducted IBM SPSS Statistics and GraphPad Prism. RESULTS: Circulating sfrp5 level was significantly decreased in T2D and LADA patients plasma compared with that in healthy control (14.14+/ 11.91ng/mL, 14.82+/-11.27ng/mL, 22.98+/-12.36ng/mL, respectively), although no differences was observed between LADA and T2D groups. Furthermore, we found sfrp5 was correlated with homeostasis model assessment of insulin resistance (HOMA-IR), diabetes duration and BMI. Finally we found sfrp5 was still negatively correlated with HOMA-IR after being adjusted for disease duration and BMI(r= -0.315, P< 0.05). CONCLUSIONS: Our results support a role for SFRP5 as a protective factor in the pathogenesis of autoimmune diabetes and facilitate a novel aspect for diabetes research. PMID- 26150853 TI - Presence and distribution of dental enamel defects, recurrent aphthous lesions and dental caries in children with celiac disease. AB - OBJECTIVE: To determine presence and distribution of enamel defects, recurrent oral aphthous lesions (RAS) and dental caries in children with Celiac Disease (CD) and compare the results with a healthy control group. METHODS: Twenty- five CD patients age between 4- 16 years with no other systemic disease, were examined in Pediatric Gastroenterology Clinic of Erciyes University, Faculty of Medicine (Kayseri, Turkey) and then referred to Department of Pediatric Dentistry, Faculty of Dentistry for dental examination and treatment. The control group (25 patients) consisted healthy patients referred to the Department of Pediatric Dentistry, Faculty of Dentistry, Erciyes University for restorative treatment. Both the CD group and control group was examined by the same investigator for the following; (1) enamel defects, (2) recurrent aphthous stomatitis, (3) dental caries. RESULTS: The mean dmft values for the CD group and control group were 3.25+/-3.25 and 4.56+/-2.87 respectively. The difference was not statistically significant.(P>0.05). The mean DMFT values for the CD and the control group were 3.75+/-2.62 and 1.83+/-1.7, respectively. There was a significant difference between the two groups (P<0.01). The prevalence of enamel defects and recurrent apthous stomatitis (RAS) was greater in celiac patients than in the control group. Enamel defects (in at least one permanent tooth) were observed in 12 out of 25 (48%) children in the CD group and four out of 25 children (16%).(P =0.01). Recurrent apthous stomatitis was found in 11/25 (44%) CD group, while no RAS was detected in the control group. CONCLUSION: Celiac Disease (CD) has adverse effects on oral health in term of enamel defect, recurrent aphthous stomatitis and caries score. Pediatricians and dentists especially pediatric dentists should be knowledgeable about oral symptoms of CD. Increased awareness can provide an early diagnosis and prevent long- term complications of this disease. On the other hand, further comprehensive investigations of CD patients can add to our understanding of the efficacy of CD on oral health in children. PMID- 26150854 TI - Job satisfaction among doctors, a multi-faceted subject studied at a tertiary care hospital in Lahore. AB - OBJECTIVE: To study the level of job satisfaction among doctors serving in a tertiary care hospital in Lahore and ascertain its co-relation with multiple demographic variables which had a profound impact. METHODS: This cross sectional study with non-probability purposive sampling was conducted at Combined Military Hospital, Lahore, from February 2014 to November 2014. Subjects were doctors serving in that hospital for minimum six months duration. Pre-formed questionnaires were distributed to volunteers (average filling time was 3 1/2 to 7 minutes). Multiple demographic features were independent variables. Outcome variable was job satisfaction. Statistical analysis was done via descriptive statistics (SPSS 20), data expressed as mean +/- standard deviation (SD). RESULTS: Out of 263 doctors serving in hospital, 203 (77.91%) volunteered to participate; response rate by depositing the filled forms was 47.78% (97 doctors). Amongst the respondents, 10 (10.3%) doctors had below average job satisfaction, 32(33.0%), 21(21.6%), 21(21.6%) and 13(13.3%) had average, above average, well above average and outstanding job satisfaction respectively. There was significant relation between job satisfaction and age group of the doctors (p 0.025), education (p 0.015), service years (p 0.013) income per month (p<0.001). There was no significant impact of gender (p 0.540), marital status (p 0.087), number of children (p 0.153), current employment (p 0.71), nature of job (p 0.204), working hours (p 0.089), additional duties p 0.421) and socioeconomic class (p 0.104) on outcome variable. CONCLUSION: A significant number of doctors was found discontented with their job, which may consequently impact their yield/performance. The job satisfaction can be substantially improved if these contributory factors are aptly addressed at all tiers. PMID- 26150855 TI - Molecular epidemiology and phylogenetic analysis of Dengue virus type-1 and 2 isolated in Malaysia. AB - OBJECTIVE: Detection of different serotypes of dengue virus and provide information on origin, distribution and genotype of the virus. METHODS: Dengue virus serotypes identified as DEN-1 and DEN-2 were amplified and sequenced with E gene. The consensus sequences were aligned with references E gene sequences of globally available GenBank. Phylogenetic analysis was performed using Neighbor joining and Kimura 2-parameter model to construct phylogenetic tree. RESULTS: A total of 53 dengue virus isolates were positive, of which 38 (71.7%) were DENV-1 and 15 (28.3%) were DENV-2. Phylogenetic tree of DENV-1 and DENV-2 showed that the isolates were clustered in genotype I and cosmopolitan genotype, respectively considered the predominant genotypes in Southeast Asian countries. The molecular epidemiology genotype I DENV-1 and cosmopolitan genotype DENV-2 have been co circulating in Klang Valley areas, Malaysia without shifting of genotype. CONCLUSION: The study reveals that DENV-1 and DENV-2 have been circulating in Malaysia. The isolates are clustered in genotype 1 and cosmopolitian genotype, respectively. The study results would help in planning for prevention and control of dengue virus in Malaysia. PMID- 26150856 TI - Efficacy and adverse effects of oral chelating therapy (deferasirox) in multi transfused Pakistani children with beta-thalassemia major. AB - OBJECTIVE: To determine the efficacy and adverse effects of oral chelation therapy (deferasirox) in multi-transfused beta-thalassemia major patients visiting pediatric thalassemia clinic in Civil Hospital Karachi. METHODS: This prospective study was conducted at pediatric thalassemia clinic of Civil Hospital Karachi. Hundred multi-transfused beta-thalassemia patients registered in the clinic for oral iron chelation therapy were included in the study. Information regarding clinical and laboratory parameters including abdominal pain, jaundice, serum ferritin, creatinine and serum transaminase levels were recorded on a Performa and data was analyzed through SPSS 16. RESULTS: Hundred patients were stratified into two age groups, 54% were below and 46% were above nine year. Majority were males, 62% and 38% were females. Abdominal pain 41%, nausea 31%, vomiting 15%, jaundice 15% and elevated serum creatinine 11.5% were frequently observed clinical adverse effects in this study. Serum glutamic pyruvic transaminase (SGPT) level was statistically significant compared with initial visit and six months after optimal chelation therapy (p=0.030). Although Serum ferritin was decreased but it was not statistically significant (p=0.929). CONCLUSION: Deferasirox is an effective oral chelation agent for beta-thalassemia major patients. Most common adverse effects of the drug are abdominal pain, nausea, vomiting, and elevation of liver enzymes. PMID- 26150857 TI - Dry eye disease and depression-anxiety-stress: A hospital-based case control study in Turkey. AB - OBJECTIVE: The aim of the present study was to investigate the association between dry eye disease (DED) and psychosomatic conditions, such as depression, stress, and anxiety, and the distribution of associated risk factors. METHODS: In this case control study, the sample consisted of 121 DED subjects and 242 control subjects. Each subjects was diagnosed as having DED or not by an ophthalmologist. Ocular Surface Disease Index and Depression Anxiety Stress Scales were administered to all subjects. Data were analysed using chi-square and Mann Whitney U tests as a univariate analysis and multiple logistic regression as a multivariate analysis. RESULTS: Of 1,458 consecutive outpatients, clinically diagnosed DED was present in 121 individuals (8.3%). There was a significant relationship of family history of DED (OR, 1.43; 95% CI, 0.84-2.41), chronic disease history (OR, 2.84; 95% CI, 1.66-4.87), OSDI score (OR, 1.07; 95% CI, 1.97 4.06), depression (OR, 2.06; 95% CI, 1.30-3.27), anxiety (OR, 2.66; 95% CI, 1.67 4.23), and stress (OR, 2.33; 95% CI, 1.48-3.67) with DED. CONCLUSION: Individuals with depression, anxiety and stress are more likely to experience DED. In addition to confirming some well-known risk factors, this study has found new associations between DED and a family history of DED and the presence of stress. PMID- 26150858 TI - Construction of finite element model and stress analysis of anterior cruciate ligament tibial insertion. AB - OBJECTIVE: The aim of the present study was to develop a more realistic finite element (FE) model of the human anterior cruciate ligament (ACL) tibial insertion and to analyze the stress distribution in the ACL internal fibers under load. METHODS: The ACL tibial insertions were processed histologically. With Photoshop software, digital images taken from the histological slides were collaged, contour lines were drawn, and different gray values were filled based on the structure. The data were exported to Amira software and saved as ".hmascii" file. This document was imported into HyperMesh software. The solid mesh model generated using HyperMesh software was imported into Abaqus software. The material properties were introduced, boundary conditions were set, and load was added to carry out the FE analysis. RESULTS: The stress distribution of the ACL internal fibers was uneven. The lowest stress could be observed in the ACL lateral fibers under tensile and shear load. CONCLUSION: The establishment of ACL tibial insertion FE model and mechanical analysis could reveal the stress distribution in the ACL internal fibers under load. There was greater load carrying capacity in the ACL lateral fibers which could sustain greater tensile and shear forces. PMID- 26150859 TI - Postgraduate education needs of Nurses' who are caregivers for patients with diabetes. AB - OBJECTIVE: Diabetic management process requires nurses with expert knowledge and patient care skills. This study was carried out to identify nurses' diabetic care approaches and their post graduate education needs in order to develop a "Basic Diabetes Patient Care Education Program" in a university hospital in Turkey. METHODS: The descriptive study, using the survey technique, was carried out in a university hospital with 87 bedside nurses who were caring for diabetic patients. Investigators developed data collection tool consisting of closed ended questions and opportunities for open-ended responses. RESULTS: Among the 87 nurses, 88.5% were staff nurses, and 11.5% were nurse managers. The mean age was 27.41 +/- 4.82 and years of professional experience was 6.86 +/- 4.23. The 41.4% of nurses stated that they were caring for 1-2 patients with diabetes per week and 72.4% of nurses stated that they had attended an educational session about diabetes after graduation. The 95.4% of nurses reported a need for a continuous education program for diabetes patient care. Medication regimen (69.0%) and special care applications such as wound care (54.0%) were the most needed educational requirements. There were no difference in educational needs based on basic education or years of professional experience (p>0.05). CONCLUSIONS: Nurses caring for patients with diabetes should be supported by orientation, in-service education and continuing education programs. Additionally, the placement of patient care courses for chronic diseases, like diabetes, into the core curriculum of nursing schools would be useful in responding to actual patient care and family needs. PMID- 26150860 TI - Fetomaternal outcome of pregnancy with Mitral stenosis. AB - OBJECTIVE: To evaluate the frequency of fetomaternal outcome of pregnancy with Mitral stenosis admitted in Civil Hospital Karachi. METHODS: It was a two years descriptive study done in the Department of Obstetrics and Gynaecology Civil Hospital Karachi. All pregnant women with a known or newly diagnosed Mitral stenosis on echocardiography were included in the study. History was taken regarding age, parity, gestational age (calculated by ultrasound) and complaints. Mode of delivery and Maternal mortality noted. Foetal outcome was analyzed by birth weight and Apgar score. RESULTS: A total of 101 patients meeting the inclusion criteria were enrolled in the study. The ages of the women ranged between 20-29 years (69%) and 81% were multigravidas. Vaginal delivery occurred in 67 (66.3%) women and 78.3% were term pregnancies. Preterm deliveries were 21.8% and 27.7% newborns were low birth weight. APGAR score <7 was found in 14.9% of neonates and 9 babies had intrauterine death. Low ejection fraction<55% was diagnosed in 20(13.9%) women and Maternal mortality was found in two cases. CONCLUSION: Heart disease in pregnancy is associated with significant morbidity, it should be carefully managed in a tertiary care hospital to obtain optimum maternal and foetal outcome. PMID- 26150861 TI - Correlation between genetic polymorphism of matrix metalloproteinase-9 in patients with coronary artery disease and cardiac remodeling. AB - OBJECTIVE: To explore the correlation between genetic polymorphism of matrix metalloproteinase-9 (MMP-9) in patients with coronary artery disease (CAD) and cardiac remodeling. METHODS: A total of 272 subjects who received coronary angiography in our hospital from July 2008 to September 2013 were selected, including 172 CAD patients (CAD group) and another 100 ones (control group). Both groups were subjected to MMP-9 and ultrasonic detections to determine vascular remodeling and atherosclerotic plaques. C1562G polymorphism of MMP-9 gene was detected, and correlation with vascular remodeling and atherosclerotic plaque was analyzed. RESULTS: Serum MMP-9 level of CAD group (330.87+/-50.39 ng/ml) was significantly higher than that of control group (134.87+/-34.02 ng/ml) (P<0.05). Compared with control group, CAD group had significantly higher intima-media thickness, and significantly lower systolic peak velocity, mean systolic velocity and end-diastolic velocity (P<0.05). Total area of stenotic blood vessels was 67.34+/-22.98 mm(2), while that of control blood vessels was 64.00+/-20.83 mm(2). G/G, G/C and C/C genotype frequencies of MMP-9 differed significantly in the two groups (P<0.05). G and C allele frequencies of CAD group (70.9% and 29.1%) were significantly different from those of control group (50.0% and 50.0%) (P<0.05). G/G, G/C and C/C genotypes were manifested as lipid-rich, fibrous and calcified or ulcerated plaques respectively. Total area of stenotic blood vessels of G/G genotype significantly exceeded those of G/C and C/C genotypes (P<0.05), whereas the latter two had no significant differences. CONCLUSION: CAD promoted 1562C-G transformation of MMP-9 gene into genetic polymorphism, thus facilitating arterial remodeling and increasing unstable atherosclerotic plaques. PMID- 26150862 TI - Comparison of frequency of asymptomatic microhematuria in patients with stage 2-4 versus stage 0-1 pelvic organ prolapse. AB - OBJECTIVE: To compare the frequency of asymptomatic microhematuria (AMH) in patients with stage 2-4 and stage 0-1 pelvic organ prolapse (POP). METHODS: The hospital database was searched for women diagnosed with pelvic floor disorders and all medical records were reviewed retrospectively for the presence of AMH. An additional search was conducted for women with other benign gynecological conditions such as myoma uteri, endometrial hyperplasia or adnexal masses without evidence of pelvic organ prolapse (control group). The control group was created using 1:1 matching for age and menopausal status. The frequency of AMH in these patients were compared. The degree of hematuria was categorized as reported by the laboratory as 3 to 25 (low grade hematuria), 26 to 50 (intermediate grade hematuria) and 51 or more (high grade hematuria) red blood cell/high powered field. RESULTS: AMH is statistically significant more often seen in study group than in control group (p:0.016). In the prolapse group 20 women (13.7%) had AMH compared with 9 (6.2%) in the control group. All of 29 patients with AMH had low grade hematuria defined as < 25 red blood cell/high powered field. Patients were followed up for 22 +/- 7 (12 to 33) months. No bladder cancer and no cancer of the upper urinary tract has been detected in these 29 patients with AMH during follow-up. CONCLUSIONS: Women with stage 2-4 POP are more likely to be diagnosed with AMH than those with stage 0-1 prolapse. PMID- 26150863 TI - Candida isolates from pregnant women and their antifungal susceptibility in a Malaysian tertiary-care hospital. AB - OBJECTIVE: Pregnant women are susceptible to vaginal colonization and infection by yeast. The purpose of the study was to determine the prevalence of Candida spp in high vaginal swabs of pregnant women and their antifungal susceptibility. METHODS: High vaginal swab samples received from Serdang Hospital, Selangor, Malaysia during 2011 initially had microscopic examination, Gram-staining and fungal culture. These were finally confirmed by growth in chromogenic medium (CHROMagarCandida; Difco BBL, USA) and commercial biochemical identification kit (API 20C AUX; bioMerieux, Lyon, France). Antifungal susceptibility was performed by E-test method. RESULTS: Out of 1163 specimens 200 (17.2%) candida spp were confirmed from high vaginal swabs of pregnant women. Candida albicans (83.5%) is the most common species detected followed by Candida glabrata (16%) and Candida famata (0.05%). All C. albicans and C.famata isolates were susceptible to fluconazole while C.glabrata isolates were dose dependent susceptibility. First and second trimester, and diabetes were considered significant factors in patients for the vaginal candidiasis (p < 0.001). CONCLUSIONS: In pregnant women, C. albicans was the frequently isolated yeast from high vaginal swabs. Routine screening and treatment are important of pregnant women regardless of symptoms. PMID- 26150864 TI - Cognitive failure, teacher's rejection and interpersonal relationship anxiety in children with dyslexia. AB - OBJECTIVES: Present research aimed to explore relationship between cognitive failure, teacher's rejection (TR), interpersonal relationship anxiety (IRA) and Signs of Dyslexia (SD) in children with dyslexia. Another aim was to explore TR, SD and IRA as predictors of cognitive failure and final aim was to see TR, SD and cognitive failure as predictors of IRA. METHOD: Sample included140 students (70 girls & 70 boys) with dyslexia. Their age was ranged between 7-14 years (mean age: M=10.50, SD= 1.89). Cognitive Failure Questionnaire, Teacher's Acceptance Rejection Questionnaire and Interpersonal Relationship Anxiety Questionnaire were used for assessment. RESULTS: Results revealed significant positive relationship between cognitive failure, TR, SD and IRA. TR, SD, IRA emerged as significant predictors of cognitive failure while TR, SD and cognitive failure emerged as significant predictors of IRA. CONCLUSION: Findings from the present research have practical implications for parents, teachers, trainers and health physicians while dealing children with dyslexia. PMID- 26150865 TI - Complete blood count parameters may have a role in diagnosis of gestational trophoblastic disease. AB - OBJECTIVE: The goal of this study was to investigate whether gestational trophoblastic disease (GTD) and healthy pregnancy differ with respect to complete blood count parameters and these parameters can be used both to explain the pathophysiologic mechanisms and differentiate the two conditions from each other. METHODS: The data obtained from 37 women with GTD and 61 healthy pregnancies (control group) regarding platelet (PLT), mean PLT volume (MPV) and PLT distribution width (PDW), and white blood cell (WBC) levels were evaluated. Patients with GTD were further subdivided into two groups composed of 20 partial mole (PM) and 17 complete mole (CM) cases. RESULTS: PDW and WBC were lower in the GTD than the control. There were no differences for PLT and MPV. WBC was lower in PM and both WBC and PDW were lower in CM compared with control. ROC curve analysis revealed an area under curve (AUC) 75.5% for WBC and AUC 69.3% for PDW. A cut-off value was determined 8.19 for WBC with 81.0% sensitivity and 54.1% specificity. While, 15.85 were accepted for PDW, with 87.9% sensitivity and 44.4% specificity. CONCLUSION: Lower WBC in GTD may suggest that molar pregnancy requires a lower inflammatory reaction facilitating trophoblastic invasion. Lower PDW as an indicator of platelet activation in CM may suggest that CM requires less PLT activation than healthy pregnancy that needs stronger trophoblast invasion for normal placental development. Decreased PDW levels especially < 15.85 and WBC levels < 8.19 may alert clinicians for risk of GTD. PMID- 26150866 TI - Effects of Ringer's sodium pyruvate solution on serum tumor necrosis factor-alpha and interleukin-6 upon septic shock. AB - OBJECTIVE: To study the effects of Ringer's sodium pyruvate solution on tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) upon septic shock. METHODS: Ninety emergency patients with septic shock were divided into a treatment group and a control group by random draw. The control group was resuscitated with 50 ml of compound sodium chloride (Ringer's solution), and the treatment group was given 50 ml of Ringer's sodium pyruvate solution. Both groups were basically treated. RESULTS: All patients were successfully resuscitated. After treatment, extravascular lung water index, intrathoracic blood volume index, systemic vascular resistance index and cardiac index of the two groups were significantly improved compared with those before treatment (P<0.05). However, there were no significant inter-group differences at different time points (P>0.05). Blood lactic acid level, central venous oxygen saturation index and urine output were also improved after treatment, with significant inter-group differences (P<0.05). Serum TNF-alpha and IL-6 levels of both groups significantly decreased after treatment (P<0.05), and the levels of the treatment group were significantly lower than those of the control group (P<0.05). During 28 days of follow-up, the mortality rate of the treatment group (4.4%) was significantly lower than that of the control group (20.0%) (P<0.05). CONCLUSION: Patients with septic shock are complicated with disordered expressions of inflammatory factors. During resuscitation, Ringer's sodium pyruvate solution can effectively promote blood circulation, mitigate inflammation and maintain acid base equilibrium, thus decreasing the prognostic mortality rate. PMID- 26150867 TI - Expediting support for the pregnant mothers to obtain antenatal care at public health facilities in rural areas of Balochistan province, Pakistan. AB - OBJECTIVES: To identify, and compare relative importance of, factors associated with antenatal care (ANC) utilization in rural Balochistan, toward framing a policy to increase such utilization. METHODS: This cross sectional study was conducted among 513 pregnant women in Jhal Magsi District, Balochistan, in 2011. A standardized interviewer-administered questionnaire was used. Predisposing, enabling, and reinforcing factors were evaluated with generalized linear models (Poisson distribution and log link). RESULTS: Prevalence of any ANC was only 14.4%. Predisposing, enabling, and reinforcing factors were all important determinants of ANC utilization. Reinforcing factors were clearly most important, husband's support for ANC was more important than support from other community members. Among predisposing factors, higher income, education, occupation, and better knowledge regarding benefits of ANC were positively and statistically significantly associated with ANC However increased number of children showed negative association. Complications free pregnancy showed positive significant association with ANC at public health facility among enabling factors. CONCLUSION: It is very important to increase antenatal care utilization in the study area and similar areas. Policy to achieve this should focus on enhancing support from the husband. PMID- 26150868 TI - Comparing effects of low and high-flow anesthesia on hemorheology and coagulation factors. AB - OBJECTIVES: In the current study, we compared the effects of low- and high-flow anesthesia techniques on hemorheology and coagulation parameters in patients who received sevofluran. METHODS: Forty patients classified as Risk Group I-II according to American Society of Anesthesiologists' (ASA) guidelines who were scheduled to undergo general anesthesia were randomly assigned to one of two groups. Low-flow anesthesia was administered to the first group, and high-flow anesthesia was used in the second group. Blood samples were obtained in the preoperative and peroperative periods (at 60 and 120 min) for determination of blood and plasma viscosity, plasma oncotic pressure, international normalized ratio (INR), phorotrombin time (PT), activated partial phorotrombin time (aPTT) and fibrinogen. Blood was also drawn for analysis of factor VIII (FVIII) activity, which was measured in the preoperative period and at postoperative six hour. RESULTS: The peroperative plasma viscosity was significantly low in Group 1 relative to Group 2. aPTT was significantly elevated at 60 minutes in Group 1 relative to Group 2, but the increase at 120 minutes was not significant. CONCLUSION: The effects of low-flow anesthesia on hemorheology were greater than those of high-flow anesthesia. PMID- 26150869 TI - Electrodiagnostic approach in entrapment neuropathies of the median and ulnar nerves. AB - OBJECTIVE: The present study's aim was to analyze the late responses' parameters in order to determine the utility of each one. METHODS: The study, conducted on a total of 325 patients with entrapment neuropathy of the median nerve and 36 with entrapment neuropathy of the ulnar nerve, included the bilateral evaluation of the median and the ulnar nerve and analysis of 20 F-wave and 4 A-wave parameters. RESULTS: The authors emphasize the necessity of bilateral examination and that of examining the ipsilateral ulnar/median nerve, such as to calculate the difference in F-wave average latency of the median/ulnar and the ipsilateral ulnar/median nerve. This was the most sensitive parameter studied, altered in more than 70% of cases, significantly in more cases than when using only the M-wave distal latency. Also there was a statistically significant correlation between patient age and F-wave latency. CONCLUSIONS: The completed research yielded the recommendation for F-wave parameter studies to include the difference in F-wave average latency of the median/ulnar and the ipsilateral ulnar/median nerve. This parameter was also included in the composite score, along with the recommendations of the American Academy of Emergency Medicine (AAEM). PMID- 26150870 TI - Frequency and outcome of treatment in polycystic ovaries related infertility. AB - BACKGROUND: Infertility is defined as inability of couple to conceive after one year of unprotected intercourse. The prevalence of infertility in Pakistan is 21.9%. The most common cause of medically treatable infertility is polycystic ovarian syndrome (PCO). This study was conducted to see the frequency and outcome of treatment in PCOs related infertility in infertile couples coming to Mohammad Medical College Hospital, Mirpurkhas, Sindh. METHODS: This prospective observational study was conducted at Muhammad Medical College for three years from 2005 to 2008. Total 1289 infertile couples were included in this study. RESULT: The frequency of PCOs in female related infertility was 38.5%. Other causes of female infertility were in the frequency of 44% pelvic inflammatory disease, 12.3% endometriosis, 2.9% hyperprolactenemia, and 1.35% hypothyroidism. Patients with PCOS were given different treatment modalities. One hundred fifty patients with PCO were given ovulation induction with clomephene citrate and out of them 109 (72%) conceived. Sixty three women were given combination of clomephene citrate and Metformin. Out of them 50 (79%) conceived. Five patients were given gonadotrophins, Out of them 2 (40%) patients conceived. Five patients had laparoscopic drilling out of them 3 (60%) conceived. CONCLUSION: In contrast to the literature review Polycystic Ovarian Syndrome turned out to be the second most common cause of female related infertility. But as the international literature shows it had very good out come after medical and /or surgical treatment. PMID- 26150871 TI - The effect of total hysterectomy on sexual function and depression. AB - BACKGROUND & OBJECTIVES: To investigate whether the operations of Type 1 hysterectomy and bilateral salpingo-oophorectomy performed for benign reasons have any effect on sexual life and levels of depression. METHOD: This is a multi center, comparative, prospective study. Healthy, sexual active patients aged between 40 and 60 were included into the study. Data was collected with the technique of face-to-face meeting held three months before and after the operation by using the demographic data form developed by the researchers i.e. the Female Sexual Function Index (FSFI) and the Beck Depression Scale (BDS). RESULTS: In the post-operative third month, there was an improvement in dysuria in terms of symptomatology (34% and 17%, P<0.001), while in FSFI (41.47+/-25.46 to 34.20+/-26.67, P<0.001) and BDS (12.87+/-11.19 to 14.27+/-10.95, P=0.015) there was a deterioration. For FSFI, 50-60 age range, extended family structure; and for BDS, educational status, not working and extended family structure were statistically important confounding factors for increased risk in the post operative period. CONCLUSION: While hysterectomy and bilateral salpingo oophorectomy performed for benign reasons brought about short-term improvement in urinary problems after the operation for sexually active and healthy women, they resulted in sexual dysfunction and increase in depression. The age, educational status, working condition and family structure is also important. PMID- 26150872 TI - Comparative analysis of serum iron, serum ferritin and red cell folate levels among breast fed, fortified milk and cow's milk fed infants. AB - OBJECTIVE: Iron and folic acid are essential nutrients needed for hematopoiesis. Infants' diet is commonly deficient in these micronutrients that lead to nutritional anemia. Aim of this study was to determine serum iron, serum ferritin and red cell folate levels among healthy breast fed, fortified milk and cow's milk fed infants. METHODS: A total of 120 infants of 4-9 months of age were enrolled in this study. It included 40 normal breast fed controls, 40 fortified milk fed (FM) and 40 cow's milk fed (CM) infants. Serum iron, serum ferritin and red cell folate concentrations were determined using colorimetric and enzyme immunoassay techniques. RESULTS: Mean serum iron, serum ferritin and red cell folate concentrations of breast fed control group were 120.9+/-68.4ug/dl, 109+/ 71.7ng/ml and 1044.1+/-409.2ng/ml respectively. Fortified milk (FM) group showed significantly decreased serum iron (p<0.003) as compared with controls whereas serum ferritin and red cell folate values showed insignificant change (p=0.25 and p=0.85 respectively). However serum iron, serum ferritin and red cell folate were significantly decreased in cow's milk fed (CM) group as compared with control subjects (p<0.04, p<0.006, p<0.02 respectively). Comparison of these biochemical parameters between FM and CM groups showed statistically significant difference of serum ferritin and red cell folate among cow's milk group (p<0.0001 and p<0.02) whereas serum iron level showed no significant difference, a p-value being 0.38. CONCLUSION: Healthy breast fed infants do not need any supplementation and fortification of iron and folic acid. Fortified milk appears to be an acceptable alternative in the absence of breast milk whereas cow's milk is a poor source of iron and folic acid in infants. PMID- 26150873 TI - Role of Surgery in locally advanced prostate cancer. AB - A significant proportion of patients present with locally advanced prostate cancer with inherent higher risk of local recurrence and systemic relapse after initial treatment. Recent literature favors combination of radiation therapy and extended hormonal therapy for this subset of patients. The effectiveness of Radical prostatectomy (RP) alone for locally advanced prostate cancer is controversial and is a focus of debate. However, it can decrease the tumor burden and allows the accurate and precise pathological staging with the need for subsequent treatment. Comparison of RP and other treatment modalities is difficult and incorrect because of inherent selection bias. RP as a part of multi modality treatment (with neo-adjuvant hormonal therapy (HT) and with adjuvant or salvage radiation therapy (RT)/HT) can provide long term overall and cancer specific survival. Surgical treatment (such as transurethral resection (TUR), JJ stenting and percutaneous nephrostomy (PCN) placement etc.) can also provide symptomatic improvement and palliative care to improve quality of life of patients with advanced prostate cancer. SOURCES OF DATA/STUDY SELECTION: The articles published between years 1998-2014 were searched on electronic databases Pubmed, Science direct, Google scholar and Embase and used for preparation of this review. PMID- 26150874 TI - Performance improvement indicators of the Medical Records Department and Information Technology (IT) in hospitals. AB - Medical Record Department (MRD) has a vital role in making short and long term plans to improve health system services. The aim of this study was to describe performance improvement indicators of hospital MRD and information technology (IT). COLLECTION OF DATA: A search was conducted in various databases, through related keywords in articles, books, and abstracts of conferences from 2001 to 2009. About 58 articles and books were available which were evaluated and finally 15 of them were selected based on their relevance to the study. MRD must be capable of supporting tasks such as patient care and continuity, institute management processes, medical education programs, medical research, communication between different wards of a hospital and administrative and medical staff. The use of IT in MRD can facilitate access to department, expedite communication within and outside department, reduce space with electronic medical records, reduce costs, accelerate activities such as coding by use of coding guide software and facilitate retrieval of records that will ultimately improve the performance of MRD. PMID- 26150875 TI - Thoracoscopic excision of two bronchogenic cysts located in highest upper mediastinum: Report of two cases. AB - Bronchogenic cysts are rare congenital malformation that need surgical removal. To date, bronchogenic cysts located in highest upper mediastinum excised by thoracoscopy have not been reported, though complete thoracoscopic extirpation of a bronchogenic cyst has been reported before. We excised two highest upper bronchogenic cysts by thoracoscopy successfully without any postoperative complication, demonstrating thoracoscopy could be a first-line therapeutic option even for highest upper mediastinum brochogenic cysts. PMID- 26150877 TI - Proceedings of EMMJ6 Medical Journals Conference held at Shiraz Iran (February 18 20, 2015). PMID- 26150876 TI - Retroperitoneal Ganglioneuroma: Mimicking an ovarian mass in a child. AB - Ganglioneuroma are rare, benign neural tumor of sympathetic nervous system originating from neural crest sympathogonia. Pelvic ganglioneuromas may mimic ovarian masses. We present a patient operated with the diagnosis of ovarian tumor which had a pelvic gangliuoneuroma. CASE: An eleven-year old female patient complaining of abdominal pain and a mass was seen at our hospital. On examination a 10*10 cm mass was palpable in the pelvis. Laboratory parameters were all normal and the tumor markers such as beta-HCG, AFP, CEA, serum catecholamines were negative. Abdominal ultrasonography and computed tomography showed an 11*6*9 cm solid mass containing calcification. The preoperative diagnosis was an adnexal mass of ovary. The patient was operated under general anesthesia and we found a retroperitoneal mass attached to the spine at L5. The tumoral mass was completely excised. Histopathological examination of tumor was reported as ganglioneuroma. The patient was discharged on seventh day of hospitalization with no neurological deficit. Retroperitoneal ganglioneuromas are usually present with local mass a benign tumoral course. The preoperative diagnosis may be difficult in pelvic ganglioneuromas due to close similarity with the ovarian masses. The treatment of the ganglioneuroma is total surgical excision and histology provides a confirmatory diagnosis. PMID- 26150878 TI - Proceedings of Second International conference on Medical Writing held at Ajman, UAE (March 5-7, 2015). PMID- 26150879 TI - The efficacy of platelet activation indicators for the diagnosis of tubal ectopic pregnancy. PMID- 26150880 TI - Pharmacy students are vital to the future of the profession / Les etudiants en pharmacie moteur du changement. PMID- 26150881 TI - The value of laboratory values: A community pharmacy perspective. PMID- 26150882 TI - AntiC: A practice tool for the safe use of oral chemotherapeutics by community and hospital pharmacists. PMID- 26150883 TI - Interprofessional student-run primary health care clinics: Educational experiences for pharmacy students. PMID- 26150884 TI - Ontario pharmacists' perceptions of the Pharmaceutical Opinion Program. PMID- 26150886 TI - Advocacy in pharmacy: Changing "what is" into "what should be". PMID- 26150885 TI - Do wearable activity trackers have a place in pharmacies? PMID- 26150887 TI - Practice recommendations for Parkinson's disease: Assessment and management by community pharmacists. PMID- 26150888 TI - Statins and their effect on cognition: Let's clear up the confusion. PMID- 26150889 TI - Interprofessional student-run primary health care clinics: Implications for pharmacy education in Scotland. AB - INTRODUCTION: Interprofessional student-run primary health care clinics have been a flagship model of health professional education in Canada for many years. The purpose of this study was to determine if there is support for implementing this educational model in the United Kingdom and to highlight the implications for pharmacy education in Scotland. METHOD: A cross-sectional postal survey of 3000 randomly selected citizens of Aberdeen city and shire, Scotland, aged 18 years and older. RESULTS: Of the 824 questionnaires that were returned (response rate 27.5%), more than half of the respondents (62.4%; n = 514) would consider accessing health care from a student-led, walk-in service. The range of services they expect to see includes general health checks (60%; n = 494), help for sexually transmitted diseases (57.5%; n = 474), weight management (56.8%; n = 468), smoking cessation (54.4%; n = 448) and drug misuse services (47.2%; n = 387). Concerns raised pertained to student ability, suitability for children and accessibility. Many comments pertained to the improvement of the current system by offering after-hours care. DISCUSSION: The positive response from the general public towards an interprofessional student-run primary health care clinic in Aberdeen suggests that this Canadian model of interdisciplinary health professional education would likely be a successful addition to the pharmacy curriculum in Scotland. PMID- 26150890 TI - CPhA National Survey: Canadians trust pharmacists and support their enhanced role in the delivery of quality care and services. PMID- 26150891 TI - Canadian Pharmacists Conference 2015. PMID- 26150892 TI - Pareto optimization in algebraic dynamic programming. AB - Pareto optimization combines independent objectives by computing the Pareto front of its search space, defined as the set of all solutions for which no other candidate solution scores better under all objectives. This gives, in a precise sense, better information than an artificial amalgamation of different scores into a single objective, but is more costly to compute. Pareto optimization naturally occurs with genetic algorithms, albeit in a heuristic fashion. Non heuristic Pareto optimization so far has been used only with a few applications in bioinformatics. We study exact Pareto optimization for two objectives in a dynamic programming framework. We define a binary Pareto product operator [Formula: see text] on arbitrary scoring schemes. Independent of a particular algorithm, we prove that for two scoring schemes A and B used in dynamic programming, the scoring scheme [Formula: see text] correctly performs Pareto optimization over the same search space. We study different implementations of the Pareto operator with respect to their asymptotic and empirical efficiency. Without artificial amalgamation of objectives, and with no heuristics involved, Pareto optimization is faster than computing the same number of answers separately for each objective. For RNA structure prediction under the minimum free energy versus the maximum expected accuracy model, we show that the empirical size of the Pareto front remains within reasonable bounds. Pareto optimization lends itself to the comparative investigation of the behavior of two alternative scoring schemes for the same purpose. For the above scoring schemes, we observe that the Pareto front can be seen as a composition of a few macrostates, each consisting of several microstates that differ in the same limited way. We also study the relationship between abstract shape analysis and the Pareto front, and find that they extract information of a different nature from the folding space and can be meaningfully combined. PMID- 26150893 TI - Production and characterization of absorbent heat from the bark of residual Brazil nut bark (Bertholletia Excelsa l.). AB - BACKGROUND: The increasing efforts to reduce the environmental impact on the Amazon's natural resources are focusing on watercourses that pass through effluents with high concentrations of heavy metals. The adsorption by absorbent is one of the methods used to remove metallic ions. In this assignment, the preparation of activated carbon from Brazil nut bark (Bertholletia excelsa l.), which is a waste material produced from the use of seeds in foodstuffs and cosmetics, is shown. RESULTS: The absorbent was carbonized at 400 degrees C in 3 h and activated at 800 degrees C in 2 h, having received the name of AC2, and, the specific area, pore size, real and apparent densities, porosity, scanning electron microscopy (SEM) coupled to energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), pH, moisture, fixed carbon and surface functional groups by Boehm method and Fourier transformed infrared spectroscopy (FTIR) were characterized. According to the results, the carbon presented alkaline characteristic, mesoporosity, average pore diameters of 2.203 nm and specific surface area by BET of 464.835 m(2) g(-1). The efficiency of removal was performed in synthetic solutions of copper sulphate (II) pentahydrate (CuSO4.5H2O), evaluating the influence of pH, initial concentration of copper solution (II), particle diameter and time contact of the adsorbent in solution. The results of higher removal percentages were to pH 5.09, initial concentration of 50, 100 and 150 mg(-1) diameter 0.595 < D < 1.19 mm and time contact of 5 min. CONCLUSIONS: The Brazil nut bark is shown to be an important bio-waste, being an excellent alternative material for the low-cost production of activated carbon for use in processes involving iterations of adsorption. PMID- 26150896 TI - RETRACTION. AB - [This retracts the article DOI: 10.3892/etm.2014.1532.]. PMID- 26150895 TI - PubChem structure-activity relationship (SAR) clusters. AB - BACKGROUND: Developing structure-activity relationships (SARs) of molecules is an important approach in facilitating hit exploration in the early stage of drug discovery. Although information on millions of compounds and their bioactivities is freely available to the public, it is very challenging to infer a meaningful and novel SAR from that information. RESULTS: Research discussed in the present paper employed a bioactivity-centered clustering approach to group 843,845 non inactive compounds stored in PubChem according to both structural similarity and bioactivity similarity, with the aim of mining bioactivity data in PubChem for useful SAR information. The compounds were clustered in three bioactivity similarity contexts: (1) non-inactive in a given bioassay, (2) non-inactive against a given protein, and (3) non-inactive against proteins involved in a given pathway. In each context, these small molecules were clustered according to their two-dimensional (2-D) and three-dimensional (3-D) structural similarities. The resulting 18 million clusters, named "PubChem SAR clusters", were delivered in such a way that each cluster contains a group of small molecules similar to each other in both structure and bioactivity. CONCLUSIONS: The PubChem SAR clusters, pre-computed using publicly available bioactivity information, make it possible to quickly navigate and narrow down the compounds of interest. Each SAR cluster can be a useful resource in developing a meaningful SAR or enable one to design or expand compound libraries from the cluster. It can also help to predict the potential therapeutic effects and pharmacological actions of less-known compounds from those of well-known compounds (i.e., drugs) in the same cluster. PMID- 26150894 TI - Restoration of mesenchymal retinal pigmented epithelial cells by TGFbeta pathway inhibitors: implications for age-related macular degeneration. AB - BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness. Most vision loss occurs following the transition from a disease of deposit formation and inflammation to a disease of neovascular fibrosis and/or cell death. Here, we investigate how repeated wound stimulus leads to seminal changes in gene expression and the onset of a perpetual state of stimulus independent wound response in retinal pigmented epithelial (RPE) cells, a cell type central to the etiology of AMD. METHODS: Transcriptome wide expression profiles of human fetal RPE cell cultures as a function of passage and time post plating were determined using Agilent 44 K whole genome microarrays and RNA-Seq. Using a systems level analysis, differentially expressed genes and pathways of interest were identified and their role in the establishment of a persistent mesenchymal state was assessed using pharmacological-based experiments. RESULTS: Using a human fetal RPE cell culture model that considers monolayer disruption and subconfluent culture as a proxy for wound stimulus, we show that prolonged wound stimulus leads to terminal acquisition of a mesenchymal phenotype post confluence and altered expression of more than 40 % of the transcriptome. In contrast, at subconfluence fewer than 5 % of expressed transcripts have two-fold or greater expression differences after repeated passage. Protein-protein and pathway interaction analysis of the genes with passage-dependent expression levels in subconfluent cultures reveals a 158-node interactome comprised of two interconnected modules with functions pertaining to wound response and cell division. Among the wound response genes are the TGFbeta pathway activators: TGFB1, TGFB2, INHBA, INHBB, GDF6, CTGF, and THBS1. Significantly, inhibition of TGFBR1/ACVR1B mediated signaling using receptor kinase inhibitors both forestalls and largely reverses the passage-dependent loss of epithelial potential; thus extending the effective lifespan by at least four passages. Moreover, a disproportionate number of RPE wound response genes have altered expression in neovascular and geographic AMD, including key members of the TGFbeta pathway. CONCLUSIONS: In RPE cells the switch to a persistent mesenchymal state following prolonged wound stimulus is driven by lasting activation of the TGFbeta pathway. Targeted inhibition of TGFbeta signaling may be an effective approach towards retarding AMD progression and producing RPE cells in quantity for research and cell-based therapies. PMID- 26150897 TI - Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel-Crafts alkylations. AB - The first immobilization of a MacMillan's first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper catalyzed alkyne-azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a-c was tested in the asymmetric Friedel-Crafts alkylation of N methylpyrrole with alpha,beta-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles. PMID- 26150898 TI - Adsorption mechanism and valency of catechol-functionalized hyperbranched polyglycerols. AB - Nature often serves as a model system for developing new adhesives. In aqueous environments, mussel-inspired adhesives are promising candidates. Understanding the mechanism of the extraordinarily strong adhesive bonds of the catechol group will likely aid in the development of adhesives. With this aim, we study the adhesion of catechol-based adhesives to metal oxides on the molecular level using atomic force microscopy (AFM). The comparison of single catechols (dopamine) with multiple catechols on hyperbranched polyglycerols (hPG) at various pH and dwell times allowed us to further increase our understanding. In particular, we were able to elucidate how to achieve strong bonds of different valency. It was concluded that hyperbranched polyglycerols with added catechol end groups are promising candidates for durable surface coatings. PMID- 26150900 TI - 6(th) Asian PAD Workshop. PMID- 26150901 TI - The 9th Japan-Korea Joint Meeting for Vascular Surgery. PMID- 26150899 TI - DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis. AB - BACKGROUND: Although the etiology of primary biliary cirrhosis (PBC) remains enigmatic, there are several pieces of data supporting the thesis that a strong genetic predisposition and environmental factors interact to produce a selective loss of tolerance. The striking female predominance of PBC has suggested that this sex predisposition may be secondary to epigenetic alterations on the X chromosome. In the present study, we rigorously defined the X chromosome methylation profile of CD4, CD8, and CD14 cells from 30 PBC patients and 30 controls. Genomic DNA from sorted CD4, CD8, and CD14 subpopulations was isolated, sonicated, and immunoprecipitated for analysis of methylation. All products were hybridized to a custom-tiled four-plex array containing 27,728 CpG islands annotated by UCSC and 22,532 well-characterized RefSeq promoter regions. Furthermore, bisulfite sequencing was then used for validation on a subsequent group of independent samples from PBC patients and controls. Thence, expression levels of selected X-linked genes were evaluated by quantitative real-time PCR with cDNA samples from all subjects. RESULTS: We report herein that a total of 20, 15, and 19 distinct gene promoters reflected a significant difference in DNA methylation in CD4+ T, CD8+ T, and CD14+ cells in patients with PBC. Interestingly, there was hypermethylation of FUNDC2 in CD8+ T cells and a striking demethylation of CXCR3 in CD4+ T cells, which inversely correlated with CXCR3 expression levels in CD4+ T cells from early-stage PBC patients. CONCLUSIONS: Our data provides a set of genes with epigenetic alteration likely to be indicators of autoimmunity and emphasizes the role of CXCR3 in the natural history of PBC. PMID- 26150902 TI - Percutaneous Endovascular Treatment for Hepatic Artery Stenosis after Liver Transplantation: The Role of Percutaneous Endovascular Treatment. AB - BACKGROUND: To retrospectively analyze the outcomes of interventional radiology treatment of patients with hepatic artery stenosis (HAS) after liver transplantation at our Institution. MATERIAL/METHODS: Hepatic artery stenosis was diagnosed and treated by endovascular technique in 8 (2.8%) patients, who underwent liver transplantation between July 2007 and July 2011. Patients entered the follow-up period, during which we analyzed hepatic artery patency with Doppler ultrasound at 1, 3, 6, and 12 months after percutaneous endovascular treatment (PTA), and every six months thereafter. RESULTS: During the 12-month follow-up period, 6 out of 8 patients (75%) were asymptomatic with patent hepatic artery, which was confirmed by multislice computed tomography (MSCT) angiography, or color Doppler (CD) ultrasound. One patient had a fatal outcome of unknown cause, and one patient underwent orthotopic liver retransplantation (re-OLT) procedure due to graft failure. CONCLUSIONS: Our results suggest that HAS angioplasty and stenting are minimally invasive and safe endovascular procedures that represent a good alternative to open surgery, with good 12-month follow-up patency results comparable to surgery. PMID- 26150903 TI - Complementory Value of Sonography in Early Evaluation of Necrotizing Enterocolitis. AB - BACKGROUND: Despite the widespread use of plain films to detect necrotizing enterocolitis (NEC), it is considered a time-consuming method, which exposes patients to radiation. We aimed to assess changes in ultrasonographic variables and to compare sonograhy and chest radiography in detecting early stages of NEC in suspected premature infants. MATERIAL/METHODS: This case-control study was carried out in the years 2012-2013. We enrolled 67 premature neonates using a simple sampling method and divided them into the study and control groups. All patients underwent plain abdominal radiography, gray-scale and color Doppler sonography. RESULTS: 34 and 33 neonates were assigned to the study and control groups. No significant gender differences were found between the two groups (P=0.549). The mean bowel wall thickness ranged from 1.2 to 3.2 mm in the control group (132 abdominal quadrants) and 1-3.3 mm in the study group (136 abdominal quadrants, P=0.502). Intra-mural echogenic dots were seen in one neonate in the study group in favour of pneumatosis intestinalis. The mean +/-SD bowel wall perfusion in the study and control groups were 3.117+/-0.975 and 2.878+/-0.538 dots or lines/cm(2), respectively (P=0.218). One neonate in the study group showed internal echoes within the mild amount of free fluid. Twelve neonates in the control group had minimal amounts of intra-abdominal free fluid. CONCLUSIONS: The two groups differed regarding bowel wall thickness, echogenicity, and perfusion in sonograhy and color Doppler evaluation. Although those differences were not statistically significant, considering the time-consuming nature of abdominal X-ray, the use of sonograhy and color Doppler can improve diagnosis and treatment of NEC as a triage method. PMID- 26150904 TI - Spontaneous Rupture of the Middle Fossa Arachnoid Cyst into the Subdural Space: Case Report. AB - BACKGROUND: Arachnoid cysts are congenital, benign and intra-arachnoidal lesions. A great majority of arachnoid cysts are congenital. However, to a lesser extent, they are known to develop after head trauma and brain inflammatory diseases. Arachnoid cysts are mostly asymptomatic and they can develop anywhere in the brain along the arachnoid membrane. CASE REPORT: Arachnoid cysts form 1% of the non-traumatic lesions which occupy a place and it is thought to be a congenital lesion developed as a result of meningeal development abnormalities or a lesion acquired after trauma and infection. There is a male dominance at a rate of 3/1 in arachnoid cysts which locate mostly in the middle fossa. Our patient was a 2 years-old boy. CONCLUSIONS: As a conclusion, spontaneous subdural hygroma is a rare complication of the arachnoid cysts. Surgical intervention could be required in acute cases. PMID- 26150905 TI - Information structure: linguistic, cognitive, and processing approaches. AB - Language form varies as a result of the information being communicated. Some of the ways in which it varies include word order, referential form, morphological marking, and prosody. The relevant categories of information include the way a word or its referent have been used in context, for example, whether a particular referent has been previously mentioned, and whether it plays a topical role in the current utterance or discourse. We first provide a broad review of linguistic phenomena that are sensitive to information structure. We then discuss several theoretical approaches to explaining information structure: information status as a part of the grammar; information status as a representation of the speaker's and listener's knowledge of common ground and/or the knowledge state of other discourse participants; and the optimal systems approach. These disparate approaches reflect the fact that there is little consensus in the field about precisely which information status categories are relevant, or how they should be represented. We consider possibilities for future work to bring these lines of work together in explicit psycholinguistic models of how people encode information status and use it for language production and comprehension. WIREs Cogn Sci 2013, 4:403-413. doi: 10.1002/wcs.1234 This article is categorized under: Linguistics > Language in Mind and Brain Psychology > Language. PMID- 26150906 TI - Discovering relations between indirectly connected biomedical concepts. AB - BACKGROUND: The complexity and scale of the knowledge in the biomedical domain has motivated research work towards mining heterogeneous data from both structured and unstructured knowledge bases. Towards this direction, it is necessary to combine facts in order to formulate hypotheses or draw conclusions about the domain concepts. This work addresses this problem by using indirect knowledge connecting two concepts in a knowledge graph to discover hidden relations between them. The graph represents concepts as vertices and relations as edges, stemming from structured (ontologies) and unstructured (textual) data. In this graph, path patterns, i.e. sequences of relations, are mined using distant supervision that potentially characterize a biomedical relation. RESULTS: It is possible to identify characteristic path patterns of biomedical relations from this representation using machine learning. For experimental evaluation two frequent biomedical relations, namely "has target", and "may treat", are chosen. Results suggest that relation discovery using indirect knowledge is possible, with an AUC that can reach up to 0.8, a result which is a great improvement compared to the random classification, and which shows that good predictions can be prioritized by following the suggested approach. CONCLUSIONS: Analysis of the results indicates that the models can successfully learn expressive path patterns for the examined relations. Furthermore, this work demonstrates that the constructed graph allows for the easy integration of heterogeneous information and discovery of indirect connections between biomedical concepts. PMID- 26150908 TI - Encapsulating peritoneal sclerosis as a late complication of peritoneal dialysis. AB - INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a rare cause of intestinal obstruction which is characterized by fibrotic encapsulation of the bowel. Although its pathogenesis is still not clear, many etiological factors have been stated. PRESENTATION OF CASE: In this report, we present a 26-year old woman with peritoneal dialysis related EPS. Because of the unresolving intestinal obstructive symptoms, she underwent surgical intervention in which the thick dense whitish membranous sac was excised from the surrounding intestine along with adhesiolysis. She recovered uneventfully. She is symptom-free on the eight months of follow-up. DISCUSSION: EPS should be born in mind as a complication of the long term peritoneal dialysis in patients with progressive obstructive ileus and recurrent peritonitis. Its treatment either medically or surgically varies depending on the stage of this entity. CONCLUSION: Early identification of EPS is important in order to achieve better prognosis. PMID- 26150907 TI - Innate lymphocyte cells in asthma phenotypes. AB - T helper type 2 (TH2) cells were previously thought to be the main initiating effector cell type in asthma; however, exaggerated TH2 cell activities alone were insufficient to explain all aspects of asthma. Asthma is a heterogeneous syndrome comprising different phenotypes that are characterized by their different clinical features, treatment responses, and inflammation patterns. The most studied subgroups of asthma include TH2-associated early-onset allergic asthma, late-onset persistent eosinophilic asthma, virus-induced asthma, obesity-related asthma, and neutrophilic asthma. The recent discovery of human innate lymphoid cells capable of rapidly producing large amounts of cytokines upon activation and the mouse data pointing to an essential role for these cells in asthma models have emphasized the important role of the innate immune system in asthma and have provided a new means of better understanding asthma mechanisms and differentiating its phenotypes. PMID- 26150909 TI - Advances and controversies in pleural diseases. PMID- 26150911 TI - Tuberculous pleural effusions: advances and controversies. AB - On a global scale, tuberculosis (TB) remains one of the most frequent causes of pleural effusions. Our understanding of the pathogenesis of the disease has evolved and what was once thought to be an effusion as a result of a pure delayed hypersensitivity reaction is now believed to be the consequence of direct infection of the pleural space with a cascade of events including an immunological response. Pulmonary involvement is more common than previously believed and induced sputum, which is grossly underutilised, can be diagnostic in approximately 50%. The gold standard for the diagnosis of tuberculous pleuritis remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli (AFB). In high burden settings, however, the diagnosis is frequently inferred in patients who present with a lymphocytic predominant exudate and a high adenosine deaminase (ADA) level, which is a valuable adjunct in the diagnostic evaluation. ADA is generally readily accessible, and together with lymphocyte predominance justifies treatment initiation in patients with a high pre-test probability. Still, false-negative and false-positive results remain an issue. When adding closed pleural biopsy to ADA and lymphocyte count, diagnostic accuracy approaches that of thoracoscopy. The role of other biomarkers is less well described. Early pleural drainage may have a role in selected cases, but more research is required to validate its use and to define the subpopulation that may benefit from such interventions. PMID- 26150912 TI - Pneumonia and empyema: causal, casual or unknown. AB - Parapneumonic effusions complicating pneumonia are associated with increased morbidity and mortality. Along with increased mortality, complicated parapneumonic effusion and empyema often necessitate prolonged treatment, longer hospital stay and interventions. Parapneumonic effusions arise from inflammation in the lungs and pleural space from direct invasion of bacteria, cascade of inflammatory events and bacteriologic virulence features. Patient factors and comorbidities also contribute to the pathophysiology of parapneumonic effusion development. The evolution of parapneumonic effusion can be divided into three progressive stages: (I) exudative stage; (II) fibrinopurulent stage; and (III) organizing stage with pleural peel formation. These stages can help categorize effusions into groups in order to evaluate the risk of a complicated course requiring intervention. We recommend that clinical data be evaluated and a stepwise approach be taken in management of these patients. This review article discusses current understanding of the development and relationship of parapneumonic effusions with pneumonia. PMID- 26150910 TI - Pleural mesothelial cells in pleural and lung diseases. AB - During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and beta-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-beta, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need further exploration. PMID- 26150913 TI - Intrapleural tissue plasminogen activator and deoxyribonuclease therapy for pleural infection. AB - Pleural infection remains a global health burden associated with significant morbidity. Drainage of the infected pleural fluid is important but can often be hindered by septations and loculations. Intrapleural fibrinolytic therapy alone, to break pleural adhesions, has shown no convincing advantages over placebo in improving clinical outcome. Deoxyribonucleoprotein from degradation of leukocytes contributes significantly to high viscosity of infected pleural fluid. Recombinant deoxyribonuclease (DNase) is effective in reducing pleural fluid viscosity in pre-clinical studies. The combination of tissue plasminogen activator (tPA) and DNase was effective in animal model experiments of empyema. The benefits were established in a randomized clinical trial: those (n=48) treated with tPA/DNase had significantly improved radiological outcomes and reduced need of surgery and duration of hospital stay. A longitudinal observational series of 107 patients further confirmed the effectiveness and safety of tPA/DNase therapy, including its use as 'rescue therapy' when patients failed to respond to antibiotics and chest tube drainage. Overall, a short course of intrapleural tPA (10 mg) and DNase (5 mg) therapy provides a cure in over 90% of patients without requiring surgery. The treatment stimulates pleural fluid formation, enhances radiographic clearance and resolution of systemic inflammation. Serious complications are uncommon; pleural bleeding requiring transfusion occurred in ~2% of cases. Pain can occur, especially with the first dose. Treatment is contraindicated in those with significant bleeding diathesis or a bronchopleural fistula. Future research is required to optimize dosing regimens and in refining patient selection. PMID- 26150915 TI - Pleural involvement in lung cancer. AB - The pleural space, a sterile secluded environment in the thoracic cavity, represents an attractive metastatic site for various cancers of lung, breast and gastrointestinal origins. Whereas lung and breast adenocarcinomas could invade the pleural space because of their anatomic proximity, "distant" cancers like ovarian or gastrointestinal tract adenocarcinomas may employ more active mechanisms to the same end. A pleural metastasis is often accompanied by a malignant pleural effusion (MPE), an unfavorable complication that severely restricts the quality of life and expectancy of the cancer patient. MPE is the net "product" of three different processes, namely inflammation, enhanced angiogenesis and vascular leakage. Current efforts are focusing on the identification of cancer cell autocrine (specific mutation spectra and biochemical pathways) and paracrine (cytokine and chemokine signals) characteristics as well as host features (immunological or other) that underlie the MPE phenotype. Herein we examine the pleural histology, cytology and molecular characteristics that make the pleural cavity an attractive metastasis destination for lung adenocarcinoma. Mesothelial and tumor features that may account for the tumor's ability to invade the pleural space are highlighted. Finally, possible therapeutic interventions specifically targeting MPE are discussed. PMID- 26150914 TI - Switching off malignant pleural effusion formation-fantasy or future? AB - Malignant pleural effusion (MPE) is common and difficult to treat. In the vast majority of patients the presence of MPE heralds incurable disease, associated with poor quality of life, morbidity and mortality. Current therapeutic approaches are inefficient and merely offer palliation of associated symptoms. Recent scientific progress has shed light in the biologic processes governing the mechanisms behind the pathobiology of MPE. Pleural based tumors interfere with pleural fluid drainage, as well as the host vasculature and immune system, resulting in decreased fluid absorption and increased pleural fluid production via enhanced plasma extravasation into the pleural space. In order to achieve this feat, pleural based tumors must elicit critical vasoactive events in the pleura, thus forming a favorable microenvironment for tumor dissemination and MPE development. Such properties involve specific transcriptional signaling cascades in addition to secretion of important mediators which attract and activate host cell populations which, in turn, impact tumor cell functions. The dissection of the biologic steps leading to MPE formation provides novel therapeutic targets and recent research findings provide encouraging results towards future therapeutic innovations in MPE management. PMID- 26150916 TI - MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets. AB - Malignant mesothelioma remains a difficult proposition in the clinic, with few accurate molecular markers available to guide diagnosis and patient management, and a dearth of effective treatments. Recent evidence implicates microRNAs-short non-coding RNAs involved in post-transcriptional regulation of gene expression-in mesothelioma biology. Emerging evidence suggests that exploring aberrant microRNA expression will not only improve our understanding of the disease, but will also lead to the identification of new molecular biomarkers and therapeutic targets. PMID- 26150917 TI - Pleural controversies: image guided biopsy vs. thoracoscopy for undiagnosed pleural effusions? AB - Undiagnosed pleural effusions present an increasing diagnostic burden upon healthcare providers internationally. The investigation of pleural effusions often requires the acquisition of tissue for histological analysis and diagnosis. Historically there were two options for tissue biopsy: a 'gold standard' surgical biopsy or a "blind" closed pleural biopsy. Over the last decade however, image guided Tru-cut biopsies and local anaesthetic thoracoscopic (local anaesthetic thoracoscopy) biopsies have become more widespread. Image-guided techniques acquire samples under ultrasound (US) or computed tomography (CT) guidance whereas LAT involves the direct visualisation and biopsy of the pleura with pleuroscopy. Both techniques have been shown to be superior to 'blind' closed pleural biopsy for the diagnosis of pleural or metastatic malignancy. However, closed biopsy remains a viable method of investigation in areas of high incidence of tuberculosis (TB). Beyond this, each investigative technique has its own advantages and disadvantages. Image-guided biopsy is less invasive, usually carried out as an outpatient procedure, and enables tissue biopsy in frail patients and those with pleural thickening but no pleural fluid. Local anaesthetic thoracoscopy (LAT) provides diagnostic and therapeutic capabilities in one procedure. Large volume thoracentesis, multiple pleural biopsies and talc poudrage can be carried out in a single procedure. The overall diagnostic yield is similar for both techniques, although there are no large-scale direct comparisons. Both techniques share low complication rates. PMID- 26150918 TI - Pleural controversies: indwelling pleural catheter vs. pleurodesis for malignant pleural effusions. AB - Malignant pleural effusions (MPE) are frequent consequences of malignant disease and significantly impair the quality of life (QoL) of patients. There are two main options for the palliation of MPE-related symptoms: obliterating the pleural space by pleurodesis to prevent further fluid reaccumulation, or chronically draining the pleural fluid with an indwelling pleural catheter (IPC). There is controversy as to which approach is superior each having advantages and drawbacks. Pleurodesis offers a higher chance of rapid resolution of the pleural effusion with an intervention that is time limited but at the expense of a more invasive procedure, the need for a hospital stay and a higher need for repeat procedures. IPC offers an outpatient solution which is less invasive but at the cost of prolonged catheter drainages and care in a significant portion of patients who will not achieve pleurodesis. Impact on QoL, symptom relief and costs do not appear to be significantly different between the two options. Treatment of MPE should be tailored to the patient's functional status, comorbidities, prognosis and personal preferences as well as local expertise. Hybrid approaches using pleurodesis techniques and IPC concomitantly may come into play in the near future to further improve patient care. PMID- 26150920 TI - A master of masters in cardiac surgery: Lawrence H. Cohn. PMID- 26150919 TI - Pleural procedural complications: prevention and management. AB - Pleural disease is common with a rising case frequency. Many of these patients will be symptomatic and require diagnostic and/or therapeutic procedures. Patients with pleural disease present to a number of different medical specialties, and an equally broad range of clinicians are therefore required to have practical knowledge of these procedures. There is often underestimation of the morbidity and mortality associated with pleural interventions, even those regarded as being relatively straightforward, with potentially significant implications for processes relating to patient safety and informed consent. The advent of thoracic ultrasound (TUS) has had a major influence on patient safety and the number of physicians with the necessary skill set to perform pleural procedures. As the variety and complexity of pleural interventions increases, there is increasing recognition that early specialist input can reduce the risk of complications and number of procedures a patient requires. This review looks at the means by which complications of pleural procedures arise, along with how they can be managed or ideally prevented. PMID- 26150921 TI - Reduced Disparity in Vegetable Consumption in 16 Disadvantaged Black Communities: A Successful 5-Year Community-Based Participatory Intervention. AB - BACKGROUND: Data on large scale community-level interventions on fruit and vegetable consumption targeting minority communities are lacking. This study examined whether a multicommunity intervention decreased disparities in fruit and vegetable consumption. MATERIALS AND METHODS: The Racial and Ethnic Approaches to Community Health (REACH) 2010 program was conducted among 16 black communities. Five-year trends (2001-2006) in self-reported fruit and vegetable consumption among the target population were compared with trends among white and black populations in 14 states where communities were located. RESULTS: The geometric mean of combined fruit and vegetable consumption in the REACH communities increased 7.4 % (P0.001) but did not change among white and black populations in comparison states (P0.05). Increased consumption in REACH communities was higher in the lower quintiles of consumptions. The disparity in fruits and vegetables consumption between comparison white population and blacks in REACH communities decreased by 33 %-from 0.66 to 0.44 times per day. The target population of 1.2 million people consumed fruits and vegetables about 21.9 million additional times per year as a result of the REACH program. CONCLUSION: This large community-based participatory intervention successfully reduced isparities in fruit and vegetable consumption between comparison white population and 16 disadvantaged black communities. PMID- 26150923 TI - Identification of beta-hematin inhibitors in the MMV Malaria Box. AB - The Malaria Box, assembled by the Medicines for Malaria Venture, is a set of 400 structurally diverse, commercially available compounds with demonstrated activity against blood-stage Plasmodium falciparum. The compounds are a representative subset of the 20,000 in vitro antimalarials identified from the high-throughput screening efforts of St. Jude Children's Research Hospital (TN, USA), Novartis and GlaxoSmithKline. In addition, a small set of active compounds from commercially available libraries was added to this group, but it has not previously been published. Elucidation of the biochemical pathways on which these compounds act is a major challenge; therefore, access to these compounds has been made available free of charge to the investigator community. Here, the Malaria Box compounds were tested for activity against the formation of beta-hematin, a synthetic form of the heme detoxification biomineral, hemozoin. Further, the mechanism of action of these compounds within the malaria parasite was explored. Ten of the Malaria Box compounds demonstrated significant inhibition of beta hematin formation. In this assay, dose-response data revealed IC50 values ranging from 8.7 to 22.7 MUM for these hits, each of which is more potent than chloroquine (a known inhibitor of hemozoin formation). The in vitro antimalarial activity of these ten hits was confirmed in cultures of the chloroquine sensitive D6 strain of the parasite resulting in IC50 values of 135-2165 nM, followed by testing in the multidrug resistant strain, C235. Cultures of P. falciparum (D6) were then examined for their heme distribution following treatment with nine of the commercially available confirmed compounds, seven of which disrupted the hemozoin pathway. PMID- 26150922 TI - Leishmania is not prone to develop resistance to tamoxifen. AB - Tamoxifen, an antineoplastic agent, is active in vitro and in vivo against the parasitic protozoa Leishmania. As part of our efforts to unravel this drug's mechanisms of action against the parasite and understand how resistance could arise, we tried to select tamoxifen-resistant Leishmania amazonensis. Three different strategies to generate tamoxifen resistant mutants were used: stepwise increase in drug concentration applied to promastigote cultures, chemical mutagenesis followed by drug selection and treatment of infected mice followed by selection of amastigotes. For amastigote selection, we employed a method with direct plating of parasites recovered from lesions into semi-solid media. Tamoxifen resistant parasites were not rescued by any of these methods. Miltefosine was used as a control in selection experiments and both stepwise selection and chemical mutagenesis allowed successful isolation of miltefosine resistant mutants. These findings are consistent with a multi-target mode of action to explain tamoxifen's leishmanicidal properties. Considering that drug resistance is a major concern in anti-parasitic chemotherapy, these findings support the proposition of using tamoxifen as a partner in drug combination schemes for the treatment of leishmaniasis. PMID- 26150925 TI - A unique case of nontraumatic femoral neck fracture following epilepsia partialis continua. AB - People with epilepsy are more accident prone than the non-epilepsy population. Bone fractures are most often due to seizure-related falls. However, seizures themselves, in particular generalized tonic-clonic seizures, may also cause fractures, e.g. of the thoracic spine. Here, I present a man who developed focal epilepsy following a subarachnoidal hemorrhage. During a focal motor seizure with left-sided convulsions and preserved consciousness that lasted 2 hrs, he sustained a femoral neck fracture. In persons with low mineral density, as in this case, contractions associated with simple focal motor seizures may be sufficient to give rise to such a severe complication. PMID- 26150924 TI - EEG-EMG polygraphic study of dystonia and myoclonus in a case of Creutzfeldt Jakob disease. AB - We report on a patient with sporadic Creutzfeldt-Jakob disease (CJD) who showed dystonia, periodic myoclonus, and periodic sharp wave complexes (PSWCs) on EEG. The EEG-EMG polygraphic study revealed that dystonia appeared without relation to periodic myoclonus and PSWCs and that dystonia EMGs were strongly suppressed after periodic myoclonus EMGs. These findings suggest that dystonia has a pathogenesis different from that of periodic myoclonus and PSWCs, but dystonia and periodic myoclonus may be generated through the sensorimotor cortex in CJD. PMID- 26150926 TI - Determination of arginine catabolism by salivary pellet. AB - To determine the formation of ammonium from arginine by oral bacteria residing in saliva and dental plaque, an arginolytic activity assay based on the work described by Nascimento et al. [2] was developed. Following the original methodology, insufficient ammonium production could be determined. To improve the method for our research goal, the following modifications were made to the original protocols:*The following changes were made to the arginine catabolism assay resulting in a 1000-fold increase in sensitivity: (i) the salivary pellet was washed and concentrated five times resulting in the removal of low density compounds interfering with the assay, (ii) the pH of the Tris-maleate buffer was increased from 6.0 to 7.5 resulting in a better conversion of arginine to ammonium and (iii) the incubation time was increased to 3 h to ensure that non responders and salivary pellets low in cell numbers could yield detectable levels of ammonium.*Removal of a centrifuge step from the protein determination resulted in a higher protein yield improving the accuracy of the assay.*Changing from the use of the toxic, environmentally hazardous, mercury containing Nessler's reagent to a colorimetric enzyme assay achieved a safer and greener determination of ammonium concentration. PMID- 26150927 TI - The Nav channel bench series: Plasmid preparation. AB - Research involving recombinant voltage-gated sodium (Nav) channels has unique challenges. Multiple factors contribute, but undoubtedly at the top of the list is these channels' DNA instability. Once introduced into bacterial hosts, Nav channel plasmid DNA will almost invariably emerge mutagenized and unusable, unless special conditions are adopted. This is particularly true for Nav1.1 (gene name SCN1A), Nav1.2 (SCN2A), and Nav1.6 (SCN8A), but less so for Nav1.4 (SCN4A) and Nav1.5 (SCN5A) while other Nav channel isoforms such as Nav1.7 (SCN9A) lie in between. The following recommendations for Nav plasmid DNA amplification and preparation address this problem. Three points are essential:*Bacterial propagation using Stbl2 cells at or below 30 degrees C.*Bias toward slow growing, small bacterial colonies.*Comprehensive sequencing of the entire Nav channel coding region. PMID- 26150928 TI - Point-by-point compositional analysis for atom probe tomography. AB - This new alternate approach to data processing for analyses that traditionally employed grid-based counting methods is necessary because it removes a user imposed coordinate system that not only limits an analysis but also may introduce errors. We have modified the widely used "binomial" analysis for APT data by replacing grid-based counting with coordinate-independent nearest neighbour identification, improving the measurements and the statistics obtained, allowing quantitative analysis of smaller datasets, and datasets from non-dilute solid solutions. It also allows better visualisation of compositional fluctuations in the data. Our modifications include:.*using spherical k-atom blocks identified by each detected atom's first k nearest neighbours.*3D data visualisation of block composition and nearest neighbour anisotropy.*using z-statistics to directly compare experimental and expected composition curves. Similar modifications may be made to other grid-based counting analyses (contingency table, Langer-Bar-on Miller, sinusoidal model) and could be instrumental in developing novel data visualisation options. PMID- 26150929 TI - Conservation of the mycelia of the medicinal mushroom Humphreya coffeata (Berk.) Stey. in sterile distilled water. AB - Currently, there is a growing interest in obtaining and studying the biologically active compounds from higher basidiomycetes, such as Ganoderma lucidum, Lentinus edodes and Inonotus obliquus[1], but the techniques for safe long-term storage are time-consuming, susceptible to contamination, and do not prevent genetic and physiological changes during long-term maintenance [2]. A recent strategy for obtaining biologically active compounds is using mycelia submerged cultures of these mushrooms, cultured under controlled laboratory conditions [1]. However, obtaining spores of these fungi under these conditions is difficult, and in most cases the way to obtain the spores is unknown [1]. Therefore, the strategy for mycelium storage seems to be more appropriated and simple.*A modification of Castellani's method [3-7] is proposed for higher basidiomycetes, by using the mycelium of Humphreya coffeata (Berk.) Stey., whose culture filtrates demonstrated bioactivity against lymphoma cells [8].*H. coffeata (Berk.) Stey. was grown on malt extract agar with filter paper disks that were removed after 4 days, placed in tubes with sterile distilled water, and stored at 4 degrees C.*Filter paper disks with H. coffeata (Berk.) Stey. stored at 4 degrees C were confirmed to be viable for up to 18 months, with no visible morphological alterations. PMID- 26150930 TI - Recombination-assisted megaprimer (RAM) cloning. AB - No molecular cloning technique is considered universally reliable, and many suffer from being too laborious, complex, or expensive. Restriction-free cloning is among the simplest, most rapid, and cost-effective methods, but does not always provide successful results. We modified this method to enhance its success rate through the use of exponential amplification coupled with homologous end joining. This new method, recombination-assisted megaprimer (RAM) cloning, significantly extends the application of restriction-free cloning, and allows efficient vector construction with much less time and effort when restriction free cloning fails to provide satisfactory results. The following modifications were made to the protocol:*Limited number of PCR cycles for both megaprimer synthesis and the cloning reaction to reduce error propagation.*Elimination of phosphorylation and ligation steps previously reported for cloning methods that used exponential amplification, through the inclusion of a reverse primer in the cloning reaction with a 20 base pair region of homology to the forward primer.*The inclusion of 1 M betaine to enhance both reaction specificity and yield. PMID- 26150931 TI - Three dimensional dual labelled DNA fluorescent in situ hybridization analysis in fixed tissue sections. AB - Emerging studies demonstrate that three-dimensional organization of chromatin in the nucleus plays a vital role in regulating the genome. DNA fluorescent in situ hybridization (FISH) is a common molecular technique used to visualize the location of DNA sequences. The vast majority of DNA FISH studies are conducted on cultured cells due to the technical difficulties encountered using fixed tissue sections. However, the use of cultured cells poses important limitations that could yield misleading results, making in vivo analysis a far superior approach. Here we present a protocol for multiplexed three dimensional DNA FISH in mouse brain sections, which is also applicable to other tissues. Paraffin-embedded tissues could be used but the embedding and preparation of the samples is time consuming and often associated with poor antigenicity. To overcome this problem we:*developed a FISH technique using fixed, frozen cryosections;*provide specific instructions for tissue processing for proper fixation and freezing, including equilibration in sucrose gradients to maintain proper cellular structure;*include optimized permeabilization and washing steps to achieve specific signal and to limit background fluorescence in tissue sections. PMID- 26150932 TI - Macropinosome quantitation assay. AB - In contrast to phagocytosis, macropinocytosis is not directly initiated by interactions between cell surface receptors and cargo ligands, but is a result of constitutive membrane ruffling driven by dynamic remodelling of cortical actin cytoskeleton in response to stimulation of growth factor receptors. Wang et al. (2010) [13] developed a reliable assay that allows quantitative assessment of the efficiency and kinetics of macropinosome biogenesis and/or maturation in cells where the function of a targeted protein has been perturbed by pharmacological inhibitors or by knock-down or knock-out approaches. In this manuscript we describe a modified quantitative protocol to measure the rate and volume of fluid phase uptake in adherent cells. This assay:*uses fluorescent dextran, microscopy and semi-automated image analysis;*allows quantitation of macropinosomes within large numbers of individual cells;*can be applied also to non-homogenous cell populations including transiently transfected cell monolayers. We present the background necessary to consider when customising this protocol for application to new cell types or experimental variations. PMID- 26150933 TI - Determining methylation status of methylguanine DNA methyl transferase (MGMT) from formalin-fixed, paraffin embedded tumor tissue. AB - O-6-methylguanine-DNA methyltransferase (MGMT) has been associated with resistance to alkylating agent cancer therapy in Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults. Lower expression or silencing of the MGMT protein by promoter methylation has been reported to improve survival in patients with GBM [1]. This protocol describes bisulfite conversion, methylation sensitive PCR amplification and data analysis/interpretation. This protocol differs from published protocols in that it:*Describes a detailed method to measure MGMT using DNA extracted from solid tumor tissue. We have optimized the DNA extraction by using FFPE tissue blocks that contain greater than 50% tumor tissue, when non-tumor tissue was also present. Performance of this assay is compromised when lower quantities of tumor cells are used as the methylation status of tumor cells is diluted out by methylation status of normal cells.*The measurement of MGMT could be further (enhanced) optimized using a percentage of methylation ration cutoff of 2 as methylated.*The machine specifications detailed here are specific to measuring MGMT from PPFE tumor tissue. PMID- 26150934 TI - A simple high performance liquid chromatography method for determination of rebamipide in rat urine. AB - Rebamipide is a mucoprotective agent commonly used to prevent nonsteriodal anti inflammatory drug-induced gastrointenstinal side effects [1]. Human plasma and urine analysis of rebamipide utilizing high performance liquid chromatography (HPLC) have been reported [2]. Recently, we reported on the plasma levels of rebamipide in presense or absence of celecoxib or diclofenac in rats [3] using a modified HPLC method of detection developed by Jeoung et al. [4]. To tailor the method towards use in urinary rebamipide extraction and analysis, the following modifications were made:*To compensate for high concentrations of rebamipide found in urine, a new rebamipide stock solution was prepared with a final concentration of 50,000 ng/mL.*Rat urine calibration standards were obtained within the range of 50-1000 ng/mL and 1000-50,000 ng/mL.*Plasma samples were replaced with urine samples. PMID- 26150935 TI - Step-by-step quantitative analysis of focal adhesions. AB - Focal adhesions (FAs) are specialized adhesive structures which serve as cellular communication units between cells and the surrounding extracellular matrix. FAs are involved in signal transduction and actin cytoskeleton organization. FAs mediate cell adhesion, which is a critical phenomenon in cancer research. Since cells can form many and micrometer scale FAs, their quantitative analysis demands well-optimized image analysis approaches [1-3]. Here, we have optimized the analysis of FAs of MDA-MB-231 breast cancer cells. The optimization is based on proper processing of immunofluorescence images of vinculin, which is one of the markers of FAs. All image processing steps are carried out using the ImageJ software, which is freely available and in the public domain. The advantages of our method are:*The analysis steps are simplified by combining different plugins of the ImageJ program.*FAs are better detected with minimal false negatives due to optimized processing of fluorescent images.*This approach can be applied to quantify a variety of fluorescent images comprising focal and/or localized signals within a high background such as FAs, one of the many complex signaling structures in a cell. PMID- 26150936 TI - Fabrication of 3D Controlled in vitro Microenvironments. AB - Microfluidics-based lab-on-a-chips have many advantages, one of which is to provide physiologically relevant settings for cell biology experiments. Thus there is an ever increasing interest in their fabrication. Our goal is to construct three dimensional (3D) Controlled in vitro Microenvironments (CivMs) that mimic the in vivo microenvironments. Here, we present our optimized fabrication method that works for various lab-on-a-chip designs with a wide range of dimensions. The most crucial points are:*While using one type of SU-8 photoresist (SU-2075), fine tuning of ramp, dwell time, spin speed, durations of soft bake, UV exposure and development allows fabrication of SU-8 masters with various heights from 40 to 600 MUm.*Molding PDMS (polydimethylsiloxane) at room temperature for at least two days instead of baking at higher temperatures prevents not only tears and bubbles in PDMS stamps but also cracks in the SU-8 master.*3D nature of the CivMs is ensured by keeping the devices inverted during gel polymerization. PMID- 26150937 TI - Standardized chemical synthesis of Pseudomonas aeruginosa pyocyanin. AB - Preparation of the toxin pyocyanin from the bacterium Pseudomonas aeruginosa is an exacting procedure. Pyocyanin is expensive to commercially purchase. The sellers do not give out the extraction procedure. Classically, pyocyanin preparation involves complicated multi-step P. aeruginosa culturing and solvent transfer extractions. The chemical synthesis first used (1979) has not been adequately described. We devised an easily reproducible protocol which consistently decreases the time taken for synthesis, extraction and purification of pyocyanin, and increases the pure pyocyanin proportion produced. Our procedure:*Involves more purification steps (chloroform/methanol/acidification/alkalinization).*Starts with a different pH (7.4 instead of 7), and lesser concentration of phenazine methosulfate; and retrenches a rotary evaporation step.*Removes 2 lyophilization steps, and entails different solvent proportions for thin layer chromatography. As we have extracted pyocyanin both from P. aeruginosa cultures, and via chemical synthesis; we know the procedural and product-quality differences. We endorse the relative ease, safety, and convenience of using the chemical synthesis described here. Crucially, our "naturally endotoxin-free" pyocyanin can be extracted easily without using infectious bacteria. PMID- 26150938 TI - Simultaneous extraction of proteins and metabolites from cells in culture. AB - Proper sample preparation is an integral part of all omics approaches, and can drastically impact the results of a wide number of analyses. As metabolomics and proteomics research approaches often yield complementary information, it is desirable to have a sample preparation procedure which can yield information for both types of analyses from the same cell population. This protocol explains a method for the separation and isolation of metabolites and proteins from the same biological sample, in order for downstream use in metabolomics and proteomics analyses simultaneously. In this way, two different levels of biological regulation can be studied in a single sample, minimizing the variance that would result from multiple experiments. This protocol can be used with both adherent and suspension cell cultures, and the extraction of metabolites from cellular medium is also detailed, so that cellular uptake and secretion of metabolites can be quantified. Advantages of this technique includes:1.Inexpensive and quick to perform; this method does not require any kits.2.Can be used on any cells in culture, including cell lines and primary cells extracted from living organisms.3.A wide variety of different analysis techniques can be used, adding additional value to metabolomics data analyzed from a sample; this is of high value in experimental systems biology. PMID- 26150939 TI - Continuous damage parameter calculation under thermo-mechanical random loading. AB - The paper presents a method on how the mean stress effect on fatigue damage can be taken into account under an arbitrary low cycle thermo-mechanical loading. From known stress, elastoplastic strain and temperature histories the cycle amplitudes and cycle mean values are extracted and the damage parameter is computed. In contrast to the existing methods the proposed method enables continuous damage parameter computation without the need of waiting for the cycles to close. The limitations of the standardized damage parameters are thus surpassed. The damage parameters derived initially for closed and isothermal cycles assuming that the elastoplastic stress-strain response follows the Masing and memory rules can now be used to take the mean stress effect into account under an arbitrary low cycle thermo-mechanical loading. The method includes:*stress and elastoplastic strain history transformation into the corresponding amplitude and mean values;*stress and elastoplastic strain amplitude and mean value transformation into the damage parameter amplitude history;*damage parameter amplitude history transformation into the damage parameter history. PMID- 26150940 TI - A novel xylene-free deparaffinization method for the extraction of proteins from human derived formalin-fixed paraffin embedded (FFPE) archival tissue blocks. AB - Protein detection methods in formalin-fixed paraffin embedded (FFPE) tissue blocks are widely used in research and clinical setting in order to diagnose or to confirm a diagnosis of various types of diseases. Therefore, multiple protein extraction methods from FFPE tissue sections have been developed in this regard. However, the yield and the quality of proteins extracted from FFPE tissues are significantly reduced in blocks stored for longer periods of time. Regardless the protein extraction method used, tissue sections must be first deparaffinized with xylene, and then washed in serial dilutions of ethanol in order to remove the toxic organic solvent "xylene" and rehydrate the tissue. The objective of this study was first to develop a method to deparaffinize FFPE blocks that excludes the use of toxic solvent "xylene". Second minimize the time required to perform the extraction. Here we describe a method where:*The entire paraffin embedded blocks are deparaffinized and rehydrated using only hot distilled water as a substitute for both xylene and ethanol*The entire procedure takes about 15 min*Deparaffinized blocks are immediately homogenized in lysis buffer, and the obtained lysate analyzed by Western blot. With this new modified technique, we were able to successfully detect actin and AKT proteins in lysates from blocks embedded in paraffin for up to 9 years. PMID- 26150941 TI - Novel detection method for chemiluminescence derived from the Kinase-Glo luminescent kinase assay platform: Advantages over traditional microplate luminometers. AB - The efficacy of cellular signal transduction is of paramount importance for the proper functioning of a cell and an organism as a whole. Protein kinases are responsible for much of this transmission and thus have been the focal point of extensive research. While there are numerous commercially available protein kinase assays, the Kinase-Glo luminescent kinase assay (Promega) provides an easy to-use and high throughput platform for determining protein kinase activity. This assay is said to require the use of a microplate spectrophotometer capable of detecting a luminescent signal. This study shows that:*The ChemiGenius Bioimaging system (Syngene), typically used for visualizing chemiluminescence from Western blots, provides an alternative detection system for Kinase-Glo luminescence.*The novel detection system confers an advantage over traditional luminometers, in that it allows visualization of the luminescent wells, which allows for the real time analysis and correction of experimental errors (i.e. bubble formation).*Determining kinase kinetics using this detection system produced comparable results to previous studies on the same enzyme (i.e. glycogen synthase kinase 3). PMID- 26150942 TI - Alternative preparation of inclusion bodies excludes interfering non-protein contaminants and improves the yield of recombinant proinsulin. AB - The goal of simple, high-yield expression and purification of recombinant human proinsulin has proven to be a considerable challenge. First, proinsulin forms inclusion bodies during bacterial expression. While this phenomenon can be exploited as a capture step, conventionally prepared inclusion bodies contain significant amounts of non-protein contaminants that interfere with subsequent chromatographic purification. Second, the proinsulin molecules within the inclusion bodies are incorrectly folded, and likely cross-linked to one another, making it difficult to quantify the amount of expressed proinsulin. Third, proinsulin is an intermediate between the initial product of ribosomal translation (preproinsulin) and the final product secreted by pancreatic beta cells (insulin). Therefore, to be efficiently produced in bacteria, it must be produced as an N-terminally extended fusion protein, which has to be converted to authentic proinsulin during the purification scheme. To address all three of these problems, while simultaneously streamlining the procedure and increasing the yield of recombinant proinsulin, we have made three substantive modifications to our previous method for producing proinsulin:.*Conditions for the preparation of inclusion bodies have been altered so contaminants that interfere with semi preparative reversed-phase chromatography are excluded while the proinsulin fusion protein is retained at high yield.*Aliquots are taken following important steps in the procedure and the quantity of proinsulin-related polypeptide in the sample is compared to the amount present prior to that step.*Final purification is performed using a silica-based reversed-phase matrix in place of a polystyrene divinylbenzene-based matrix. PMID- 26150943 TI - Isolation and identification of membrane vesicle-associated proteins in Gram positive bacteria and mycobacteria. AB - Many intracellular bacterial pathogens naturally release membrane vesicles (MVs) under a variety of growth environments. For pathogenic bacteria there are strong evidences that released MVs are a delivery mechanism for the release of immunologically active molecules that contribute to virulence. Identification of membrane vesicle-associated proteins that can act as immunological modulators is crucial for opening up new horizons for understanding the pathogenesis of certain bacteria and for developing novel vaccines. In this protocol, we provide all the details for isolating MVs secreted by either mycobacteria or Gram-positive bacteria and for the subsequent identification of the protein content of the MVs by mass spectrometry. The protocol is adapted from Gram-negative bacteria and involves four main steps: (1) isolation of MVs from the culture media; (2) purification of MVs by density gradient ultrucentrifugation; (3) acetone precipitation of the MVs protein content and in-solution trypsin digestion and (4) mass spectrometry analysis of the generated peptides and protein identification. Our modifications are:*Growing Mycobacteria in a chemically defined media to reduce the number of unrelated bacterial components in the supernatant.*The use of an ultrafiltration system, which allows concentrating larger volumes.*In solution digestion of proteins followed by peptides purification by ziptip. PMID- 26150944 TI - Elimination of the formation of biofilm in industrial pipes using enzyme cleaning technique. AB - Currently, there is a growing demand in how to eliminate the biofilm formed in industrial pipelines, especially in food, fermentation, and water treatment industry. However, the traditional techniques for CIP (cleaning in place) are usually ineffective, superficial, halfway, and do not clean or sterilize microbes located in the inner layers of the biofilm. A recent strategy for removing the biofilm in pipes is employing enzymes to clean it in the circulating water system under an optimal condition. However, how to operate and control the whole cleaning process is difficult. Here, we will introduce the strategy of enzyme cleaning to make it more appropriated and effective.*A modification of CIP method is proposed for higher efficiency by using N-acetylmuramide glycanohydrolase as catalysts whose optimal pH and temperature is 10 +/- 1 and 45 +/- 2 degrees C, respectively.*The initial efficiency of enzyme cleaning was evaluated by testing the content of ATP in water sample using Clean-TraceTM (3M Corporation).*Lastly, the terminal water was tested with SLYM-BARTTM (HACH Corporation) to find out whether there were biofilm-forming bacteria, such as Pseudomonas aeruginosa (Lakretz et al. (2011) [1]), Pseudomonas fluorescens (O'Toole and Kolter (1998) [2]), iron bacterium, etc. PMID- 26150945 TI - New closed tube loop mediated isothermal amplification assay for prevention of product cross-contamination. AB - Loop mediated isothermal amplification (LAMP) assay, a promising diagnostic test, has been developed for detection of different pathogens of human as well as animals. Various positive points support its use as a field level test but the major problem is product cross contamination leading to false positive results. Different methods were adopted by various researchers to control this false positive amplification due to cross contamination but all have their own advantages and disadvantages. A new closed tube LAMP assay based on agar dye capsule was developed in the present study and this technique has some advantages over the other closed tube technique.*Agar at the concentration of 1.5% was used to sandwich SYBR green dye I with the aid of intradermal syringe. This agar dye capsule was placed over the LAMP reaction mixture before it was amplified.*To eliminate the hazardous nature of Ultra Violet (UV) light during result visualization of LAMP products, the present study demonstrates the use of Light Emitting Diode (LED) lights for result visualization.*LAMP was carried out for Brucella species detection using this modified techniques yielding good results without any cross contamination and LED showed similar fluorescence compared to UV. PMID- 26150946 TI - Refined separation of combined Fe-Hf from rock matrices for isotope analyses using AG-MP-1M and Ln-Spec chromatographic extraction resins. AB - A combined procedure for separating Fe and Hf from a single rock digestion is presented. In a two-stage chromatographic extraction process, a purified Fe fraction is first quantitatively separated from the rock matrix using AG-MP-1M resin in HCl. Hafnium is subsequently isolated using a modified version of a commonly applied method using Eichrom LN-Spec resin. Our combined method includes:*Purification of Fe from the rock matrix using HCl, ready for mass spectrometric analysis.*Direct loading of the matrix onto the resin that is used for Hf purification.*Collection of a Fe-free Hf fraction. PMID- 26150947 TI - The GCaMP3 - A GFP-based calcium sensor for imaging calcium dynamics in the human malaria parasite Plasmodium falciparum. AB - Calcium (Ca(2+)) signaling pathways are vital for all eukaryotic cells. It is well established that changes in Ca(2+) concentration can modulate several physiological processes such as muscle contraction, neurotransmitter secretion and metabolic regulation (Giacomello et al. (2007) [1], Rizzuto and Pozzan (2003) [2]). In the complex life cycle of Plasmodium falciparum, the causative agent of human malaria, Ca(2+) is involved in the processes of protein secretion, motility, cell invasion, cell progression and parasite egress from red blood cells (RBCs) (Koyama et al. (2009) [3]). The generation of P. falciparum expressing genetically encoded calcium indicators (GECIs) represents an innovation in the study of calcium signaling. This development will provide new insight on calcium homeostasis and signaling in P. falciparum. In addition, these novel transgenic parasites, PfGCaMP3, is a useful tool for screening and identifying new classes of compounds with anti-malarial activity. This represents a possibility of interfering with signaling pathways controlling parasite growth and development. Our new method differs from previous loading protocols (Garcia et al. (1996) [4]; Beraldo et al. (2007) [5]) since:*It provides a novel method for imaging calcium fluctuations in the cytosol of P. falciparum, without signal interference from the host cell and invasive loading protocols.*This technique could also be expanded for imaging calcium in different subcellular compartments.*It will be helpful in the development of novel antimalarials capable of disrupting calcium homeostasis during the intraerythrocytic cycle of P. falciparum. PMID- 26150948 TI - Insect cell culture in reagent bottles. AB - Growing insect cells with high air space in culture vessel is common from the early development of suspension cell culture. We believed and followed it with the hope that it allows sufficient air for optimal cell growth. However, we missed to identify how much air exactly cells need for its growth and multiplication. Here we present the innovative method that changed the way we run insect cell culture. The method is easy to adapt, cost-effective and useful for both academic and industrial research labs. We believe this method will revolutionize the way we run insect cell culture by increasing throughput in a cost-effective way. In our study we identified:*Insect cells need to be in suspension; air space in culture vessel and type of culture vessel is of less importance. Shaking condition that introduces small air bubbles and maintains it in suspension for longer time provides better oxygen transfer in liquid. For this, high-fill volume in combination with speed and shaking diameter are important.*Commercially available insect cells are not fragile as original isolates. These cells can easily withstand higher shaking speed.*Growth condition in particular lab set-up needs to be optimized. The condition used in one lab may not be optimum for another lab due to different incubators from different vendors. PMID- 26150949 TI - Modification of comet-FISH technique by using temperature instead of chemical denaturation. AB - Comet-FISH technique is an extension of commonly used comet assay. Its purpose is to determine whether primary DNA damage which comet assay detects occurred within a sequence of interest that is visualized by hybridization of fluorescent probe. Presence of the signal in comet tail indicates impaired structural integrity of sequence. Our modifications to the original comet-FISH technique described by Rapp et al. (2000) [1] include:*increase in probe binding specificity,*increased rate of successful hybridization,*simultaneous temperature denaturation of both, slide and probe. PMID- 26150950 TI - Thiol-free reducing agents in electrophoretic separations and FASP proteolytic digestions for the analysis of metal-binding proteins. AB - The analysis of the complexes between metal-based chemotherapeutic drugs and proteins in biological samples, such as cisplatin or oxaliplatin, can be a challenge due to metal strong reactivity towards S-donor molecules such as dithiothreitol (DTT) or beta-mercaptoethanol (BME), usually employed as reducing agents in electrophoretic separations and proteolytic digestions for LC-MS/MS analysis.*This protocol describes the use of the thiol-free reducing trialkylphosphines, such as tributylphosphine (TBP) and tris(2 carboxyethyl)phosphine (TCEP) as suitable reagents for the preservation of the metal-protein complexes during OFFGEL-IEF and SDS-PAGE separations, respectively.*Moreover, the filter-aided sample preparation (FASP) method is presented as an advantageous option to perform tryptic in-solution digestions of metal-protein complexes in combination with OFFGEL-IEF separations.*The FASP procedure allows including previous reduction and alkylation steps in addition to proteolysis, ensuring the preservation of the metal-protein complexes. The limited time that proteins remain in contact with the reducing agent, either TBP or even DTT, during FASP could be a key factor for its extraordinary performance on the digestion of metal-protein complexes. PMID- 26150951 TI - Use of large pieces of printed circuit boards for bioleaching to avoid 'precipitate contamination problem' and to simplify overall metal recovery. AB - Very recently bioleaching has been used for removing metals from electronic waste. Most of the research has been targeted to using pulverized PCBs for bioleaching where precipitate formed during bioleaching contaminates the pulverized PCB sample and making the overall metal recovery process more complicated. In addition to that, such mixing of pulverized sample with precipitate also creates problems for the final separation of non metallic fraction of PCB sample. In the present investigation we attempted the use of large pieces of printed circuit boards instead of pulverized sample for removal of metals. Use of large pieces of PCBs for bioleaching was restricted due to the chemical coating present on PCBs, the problem has been solved by chemical treatment of PCBs prior to bioleaching. In short,*Large pieces of PCB can be used for bioleaching instead of pulverized PCB sample.*Metallic portion on PCBs can be made accessible to bacteria with prior chemical treatment of PCBs.*Complete metal removal obtained on PCB pieces of size 4 cm * 2.5 cm with the exception of solder traces. The final metal free PCBs (non metallic) can be easily recycled and in this way the overall recycling process (metallic and non metallic part) of PCBs becomes simple. PMID- 26150952 TI - Comparative analysis and validation of the malachite green assay for the high throughput biochemical characterization of terpene synthases. AB - Terpenes are the largest group of natural products with important and diverse biological roles, while of tremendous economic value as fragrances, flavours and pharmaceutical agents. Class-I terpene synthases (TPSs), the dominant type of TPS enzymes, catalyze the conversion of prenyl diphosphates to often structurally diverse bioactive terpene hydrocarbons, and inorganic pyrophosphate (PPi). To measure their kinetic properties, current bio-analytical methods typically rely on the direct detection of hydrocarbon products by radioactivity measurements or gas chromatography-mass spectrometry (GC-MS). In this study we employed an established, rapid colorimetric assay, the pyrophosphate/malachite green assay (MG), as an alternative means for the biochemical characterization of class I TPSs activity.*We describe the adaptation of the MG assay for turnover and catalytic efficiency measurements of TPSs.*We validate the method by direct comparison with established assays. The agreement of k cat/K M among methods makes this adaptation optimal for rapid evaluation of TPSs.*We demonstrate the application of the MG assay for the high-throughput screening of TPS gene libraries. PMID- 26150953 TI - Efficient purification and concentration of viruses from a large body of high turbidity seawater. AB - Marine viruses are the most abundant entities in the ocean and play crucial roles in the marine ecological system. However, understanding of viral diversity on large scale depends on efficient and reliable viral purification and concentration techniques. Here, we report on developing an efficient method to purify and concentrate viruses from large body of high turbidity seawater. The developed method characterizes with high viral recovery efficiency, high concentration factor, high viral particle densities and high-throughput, and is reliable for viral concentration from high turbidity seawater. Recovered viral particles were used directly for subsequent analysis by epifluorescence microscopy, transmission electron microscopy and metagenomic sequencing. Three points are essential for this method:*The sampled seawater (>150 L) was initially divided into two parts, water fraction and settled matter fraction, after natural sedimentation.*Both viruses in the water fraction concentrated by tangential flow filtration (TFF) and viruses isolated from the settled matter fraction were considered as the whole viral community in high turbidity seawater.*The viral concentrates were re-concentrated by using centrifugal filter device in order to obtain high density of viral particles. PMID- 26150954 TI - Analysis of methanol and ethanol in virgin olive oil. AB - This work provides a short and easy protocol that allows the analysis of both methanol and ethanol in the static headspace of olive oil. The procedure avoids any kind of sample pre-treatment beyond that of heating the oil to allow a maximum volatile concentration in the headspace of the vials. The method's LOD is 0.55 mg kg(-1) and its LOQ is 0.59 mg kg(-1). Advantages of this method are:*Simultaneous determination of methanol and ethanol (the pre-existing Spanish specification UNE-EN 14110 only analyses methanol).*No need of equipment modifications (standard split injectors work perfectly). Use of a highly polar capillary GC column, leading in most cases to chromatograms in which only three dominant peaks are present - methanol, ethanol, and propanol (that is extremely positive for easy interpretation of results).*Use of an internal standard (1 propanol) to determine the concentration of the analytes, reducing the presence of error sources. PMID- 26150955 TI - An improved method to prepare an injectable microemulsion of the galanin-receptor 3 selective antagonist, SNAP 37889, using Kolliphor((r)) HS 15. AB - Research into the galanin-3 (GAL3) receptor has many challenges, including the lack of commercially available selective ligands. While the identification of non peptidergic GAL3 receptor-selective antagonists, 1-phenyl-3-[3 (trifluoromethyl)phenyl]iminoindol-2-one (SNAP 37889) and 1-[3-(2-pyrrolidin-1 ylethoxy)phenyl]-3-[3-(trifluoromethyl)phenyl]iminoindol-2-one (SNAP 398299) have implicated a role for GAL3 receptors in anxiety, depression and drug-seeking behaviour, a major limitation of their use is poor aqueous solubility. Previously we have used 5% dimethylsulfoxide (DMSO) with 1% hydroxypropylmethyl cellulose in saline to dissolve SNAP 37889 for intraperitoneal (i.p.) injections of rats; however this produced a micro-suspension that was not ideal. The injectable formulation of SNAP 37889 was improved as follows:*30% (w/v) Kolliphor((r)) HS 15 (Solutol HS((r)) 15) and sodium phosphate buffer (0.01 M, pH 7.4) were used as vehicles.*A smooth glass mortar and pestle was used to triturate the Kolliphor((r)) HS 15 and SNAP 37889 into a paste before addition to the sodium phosphate buffer at room temperature (RT).*The resulting mixture was vortexed until the paste was fully dissolved and the microemulsion was allowed to sit for 20 min to allow air bubbles to coalesce. PMID- 26150956 TI - Plant and metagenomic DNA extraction of mucilaginous seeds. AB - The pulp surrounding the seeds of some fruits is rich in mucilage, carbohydrates, etc. Some seeds are rich in proteins and polyphenols. Fruit seeds, like cacao (Theobroma cacao) and cupuassu (Theobroma grandiflorum), are subjected to fermentation to develop flavor. During fermentation, ethanol is produced [2-6]. All of these compounds are considered as interfering substances that hinder the DNA extraction [4-8]. Protocols commonly used in the DNA extraction in samples of plant origin were used, but without success. Thus, a protocol for DNA samples under different conditions that can be used for similar samples was developed and applied with success. The protocol initially described for RNA samples by Zeng et al. [9] and with changes proposed by Provost et al. [5] was adapted for extracting DNA samples from those described. However, several modifications have been proposed:*Samples were initially washed with petroleum ether for fat phase removal.*RNAse was added to the extraction buffer, while spermidin was removed.*Additional steps of extraction with 5 M NaCl, saturated NaCl and CTAB (10%) were included and precipitation was carried out with isopropanol, followed by washing with ethanol. PMID- 26150957 TI - Colorimetric quantification of sucrose in presence of thermo-sensitive polymers present in aqueous two-phase systems. AB - The use of biodegradable material such as simple carbohydrates and recyclable material such as thermo-sensitive polymers is in need to develop a sustainable aqueous two-phase system (ATPS) for the purification of biomolecules. Accurate determination of sucrose concentration is important in liquid-liquid equilibrium (LLE) study of carbohydrate-based ATPS. The well-established phenol-sulfuric acid method has been widely employed in the measurement of carbohydrate concentration. However, the presence of thermo-sensitive polymers, which has a lower critical solution temperature (LCST) below room temperature, in carbohydrate samples could hamper the precision of spectrophotometric analysis due to the formation of two phases or cloudiness in the sample. Thus, the following modifications were made in an attempt to eliminate the interference occurred during conventional phenol sulfuric acid assay.*The modified assay for sucrose quantification was performed at an ice-cold temperature throughout the reaction in order to avoid the interference from thermo-sensitive polymers.*This method required a sample volume of 3 MUL and hence the volume of other reagents employed was also considerably reduced.*The absorbance was measured at 520 nm which allowed a longer linearity range (0.05-7.5%, w/v). PMID- 26150958 TI - Rapid preparation of rodent testicular cell suspensions and spermatogenic stages purification by flow cytometry using a novel blue-laser-excitable vital dye. AB - Availability of purified or highly enriched fractions representing the various spermatogenic stages is a usual requirement to study mammalian spermatogenesis at the molecular level. Fast preparation of high quality testicular cell suspensions is crucial when flow cytometry (FCM) is chosen to accomplish the stage/s purification. Formerly, we reported a method to rapidly obtain good quality rodent testicular cell suspensions for FCM analysis and sorting. Using that method we could distinguish and purify early meiocytes (leptotene/zygotene stages, L/Z) from more advanced ones (pachytene, P) in guinea pig, which presents an unusually high content of early stages. Here we present an upgrade of that method with improvements that enabled the obtainment of high-purity meiotic substages also from mouse testis, namely:*Shortening of the mechanical disaggregation time to optimize the integrity of the suspension.*Elimination of the 25 MUm-filtration step to ensure the presence of large P cells.*Inclusion of a non-cytotoxic, DNA-specific, 488 nm-excitable vital fluorochrome (Vybrant DyeCycle Green [VDG], Invitrogen) instead of Hoechst 33342 (requires UV laser, which can damage nucleic acids) or propidium iodide (usually related to dead/damaged cells). As far as we know, this is the first report on the use of this fluorochrome for the discrimination and purification of meiotic prophase I substages. PMID- 26150959 TI - Glycan-specific whole cell affinity chromatography: A versatile microbial adhesion platform. AB - We have sought a universal platform for elucidating and exploiting specificity of glycan-mediated adhesion by potentially uncharacterized microorganisms. Several techniques exist to explore microbial interactions with carbohydrate structures. Many are unsuitable for investigating specific mechanisms or uncharacterized organisms, requiring pure cultures, labeling techniques, expensive equipment, or other limitations such as questionable stability, stereospecificity, or scalability. We have adapted an affinity chromatography resin as a model to overcome these drawbacks, among others. It readily allows for the quantification, selection, and manipulation of target organisms based on interactions with glycan ligands. To maximize its utility as a selective screening method, we have constructed the tool such that it:*Promotes whole-cell interactions using viable, unaltered cells.*Provides robust spatial interactions with target glycans, presented with controlled stereo-specificity, for high affinity/avidity interactions that reflect a complex in vivo matrix.*Has the ability to utilize any reducing glycan, is quick, efficient, safe, and affordable to construct, and is scalable and reusable for multiple applications. PMID- 26150960 TI - Reducing background cytokine expression in epithelial cells without serum starvation. AB - Cellular excretion of inflammatory cytokines is an important experimental read out in a wide range of molecular biology fields. The addition of serum to growth media provides the optimal growing conditions for most cell types. When studying the effect of bacteria and bacterial products on these cells serum starvation is often performed as a standard procedure [1] to avoid unwanted stimulation by the serum components. The full effect of serum starvation on cell behaviour and inflammatory responses is unknown, though it has been suggested to induce various responses that can interfere with experimental results and conclusions [2]. Serum starvation has been shown to cause cells to undergo apoptosis and autophagy [3,4] as well as superoxide production and increasing cell susceptible to inflammatory stimuli [5]. In order to study stimulation of healthy epithelial cells, a new approach was required that limited unwanted stimulation but supported normal cell growth. Analysis of different serum preparations on the background cytokine expression of renal epithelial cells demonstrated conditions in which the background cytokine expression can be reduced without the need to serum starve the cells. Endotoxin content was not found to be the most relevant factor in inducing an inflammatory response in epithelial cells. Charcoal stripped preparations of foetal bovine serum (FBS) produced the lowest background expression of IL-6 and IL-8 without the need for serum starvation.*Selection of the serum source allows for cytokine expression experiments to be performed without serum starvation.*Charcoal stripped preparations of FBS produces the lowest background cytokine expression without serum starvation.*Serum factors other than endotoxin content influence cytokine secretion. PMID- 26150961 TI - High throughput automated colorimetric method for the screening of l-lactic acid producing microorganisms. AB - Lactic acid is a valuable and fully degradable organic acid with promising applications in poly-lactic acid production (Taskila S and Ojamo, 2013 [1]). Despite their efficiency, the cost of the current lactic acid bio-processes is still an obstacle to this application (Miller et al., 2011 [2]). To ameliorate lactic acid producing strains, researchers are using mutations and metabolic engineering techniques, as well as medium optimization. All these studies necessitate a good and high throughput screening method. Currently, researchers mostly use HPLC methods which often necessitate sample preparation, are not stereospecific and do not allow high throughput. To help optimizing l-lactic acid production, we developed a high throughput colorimetric method inspired by the blood l-lactic acid detection method used for diagnosis (Lin et al., 1999 [3]).*Two sequential enzymatic reactions using l-lactate oxidase, peroxidase and ABTS (2,2'-azino-di-[3-ethylbenzthiazoine-sulfonate]), a chromogenic peroxidase substrate, are used to quantify l-lactate between 13.8 and 90 mg/l.*The accuracy of the method was ascertained before automation.*The method was successfully applied for the direct determination of l-lactate content in fungal culture supernatants. PMID- 26150962 TI - Cholinesterase assay by an efficient fixed time endpoint method. AB - Many cholinesterase assays are performed to study the inhibition of cholinesterase (ChE) activity. Frequently a large number of samples are processed and Ellman's method [1] is the most commonly used [2,3]. Activity is estimated from the increment in absorbance between two reaction times when the reaction is not stopped. Bellino et al. [4] described a method based on Ellman's method whereby the reaction was stopped with SDS and then the absorbance was measured. In these methods, the chromogen reagent 5,5'dithiobis nitro benzoic acid (DTNB) is added with the substrate and colour is monitored. Some authors pointed that the chromogen can alter cholinesterase activity [5].*A modification of Bellino's method is proposed for acetylcholine-hydrolyzing activity determinations that is based on stopping the reaction after a fixed substrate reaction time using a mixture of detergent SDS and DTNB.*The method may be adapted to the user needs by modifying the enzyme concentration and applied for simultaneously testing many samples in parallel; i.e. for complex experiments of kinetics assays with organophosphate inhibitors in different tissues. PMID- 26150963 TI - Head movement compensation in real-time magnetoencephalographic recordings. AB - Neurofeedback- and brain-computer interface (BCI)-based interventions can be implemented using real-time analysis of magnetoencephalographic (MEG) recordings. Head movement during MEG recordings, however, can lead to inaccurate estimates of brain activity, reducing the efficacy of the intervention. Most real-time applications in MEG have utilized analyses that do not correct for head movement. Effective means of correcting for head movement are needed to optimize the use of MEG in such applications. Here we provide preliminary validation of a novel analysis technique, real-time source estimation (rtSE), that measures head movement and generates corrected current source time course estimates in real time. rtSE was applied while recording a calibrated phantom to determine phantom position localization accuracy and source amplitude estimation accuracy under stationary and moving conditions. Results were compared to off-line analysis methods to assess validity of the rtSE technique. The rtSE method allowed for accurate estimation of current source activity at the source-level in real-time, and accounted for movement of the source due to changes in phantom position. The rtSE technique requires modifications and specialized analysis of the following MEG work flow steps.*Data acquisition*Head position estimation*Source localization*Real-time source estimation This work explains the technical details and validates each of these steps. PMID- 26150964 TI - Game controller modification for fMRI hyperscanning experiments in a cooperative virtual reality environment. AB - Hyperscanning, an emerging technique in which data from multiple interacting subjects' brains are simultaneously recorded, has become an increasingly popular way to address complex topics, such as "theory of mind." However, most previous fMRI hyperscanning experiments have been limited to abstract social interactions (e.g. phone conversations). Our new method utilizes a virtual reality (VR) environment used for military training, Virtual Battlespace 2 (VBS2), to create realistic avatar-avatar interactions and cooperative tasks. To control the virtual avatar, subjects use a MRI compatible Playstation 3 game controller, modified by removing all extraneous metal components and replacing any necessary ones with 3D printed plastic models. Control of both scanners' operation is initiated by a VBS2 plugin to sync scanner time to the known time within the VR environment. Our modifications include:*Modification of game controller to be MRI compatible.*Design of VBS2 virtual environment for cooperative interactions.*Syncing two MRI machines for simultaneous recording. PMID- 26150965 TI - Improved method for extraction and detection of Helicobacter pylori DNA in formalin-fixed paraffin embedded gastric biopsies using laser micro-dissection. AB - To assess the molecular events exerted by Helicobacter pylori interacting directly with gastric epithelial cells, an improved procedure for microbial DNA isolation from stained hematoxilin-eosin gastric biopsies was developed based on laser micro-dissection (LM) [1]. Few articles have described the use of LM to select and detect H. pylori genome from formalin-fixed paraffin embedded gastric tissue [2]. To improve the yield and quality of DNA isolated from H. pylori contacting intestinal epithelial cells, the following conditions were established after modification of the QIAamp DNA Micro kit. *Use of at least 25 cut sections of 10-20 MUm of diameter and 3 MUm thick with more than 10 bacteria in each cut.*Lysis with 30 MUL of tissue lysis buffer and 20 MUL of proteinase K (PK) with the tube in an upside-down position.*The use of thin purification columns with 35 MUL of elution buffer. The mean of DNA concentration obtained from 25 LM cut sections was 1.94+/- 0 .16 ng/MUL, and it was efficiently amplified with qPCR in a Bio Rad iCycler instrument. The LM can improve the sample selection and DNA extraction for molecular analysis of H. pylori associated with human gastric epithelium. PMID- 26150966 TI - Non-invasive and non-destructive measurements of confluence in cultured adherent cell lines. AB - Many protocols used for measuring the growth of adherent monolayer cells in vitro are invasive, destructive and do not allow for the continued, undisturbed growth of cells within flasks. Protocols often use indirect methods for measuring proliferation. Microscopy techniques can analyse cell proliferation in a non invasive or non-destructive manner but often use expensive equipment and software algorithms. In this method images of cells within flasks are captured by photographing under a standard inverted phase contract light microscope using a digital camera with a camera lens adaptor. Images are analysed for confluence using ImageJ freeware resulting in a measure of confluence known as an Area Fraction (AF) output. An example of the AF method in use on OVCAR8 and UPN251 cell lines is included. *Measurements of confluence from growing adherent cell lines in cell culture flasks is obtained in a non-invasive, non-destructive, label-free manner.*The technique is quick, affordable and eliminates sample manipulation.*The technique provides an objective, consistent measure of when cells reach confluence and is highly correlated to manual counting with a haemocytometer. The average correlation co-efficient from a Spearman correlation (n = 3) was 0.99 +/- 0.008 for OVCAR8 (p = 0.01) and 0.99 +/- 0.01 for UPN251 (p = 0.01) cell lines. PMID- 26150967 TI - Methodology to study polymers interaction by surface plasmon resonance imaging. AB - The surface plasmon resonance (SPR) technique has been primarily used in the field of biology, in particular for the study of antibody-antigen interactions. Recently, polymers were introduced to form inclusion complexes. We describe here, a methodology based on surface plasmon resonance imaging to study water-resistant and reversible inclusion complexes using systems which are compatible with a cosmetic use. The purpose of this study is to follow in real time the interaction between two polymers. To carry out this study: *A biochip based on a covalent binding of one "host polymer" on a gold-activated surface was developed.*The binding of the host polymer to a guest polymer was monitored.*The presence of interactions between the beta-cyclodextrins groups of the host polymer and the adamantyl functional groups of the guest polymer and the possibility of dissociating the complex were established. This technique allowed carrying out parallel assays for optimizing the amount of complexes formed, the host polymer being spotted at five concentrations. It was then possible to study the influence of the concentration in host system for two concentrations of the guest polymer. The concentration in the host polymer yielding the highest immobilization of the guest system was further determined. PMID- 26150968 TI - A simple and effective method to encapsulate tobacco mesophyll protoplasts to maintain cell viability. AB - Protoplasts have been widely used for genetic transformation, cell fusion, and somatic mutation due to the absence of a cell wall. However, without the protection of a cell wall, protoplasts are easy to rupture and aggregate during washing, collecting, and gene transfection. In this work, we propose a simple and effective silica/alginate two-step method to immobilize protoplasts with advantages in experimental manipulation and microscopic imaging, as well as in potentially studying cell biological processes such as secretion and metabolism. The proposed two-step immobilization method adopts Transwell with clear tissue culture-treated membrane to support protoplasts in the form of uniform thin layer, which has three unique properties. *The tissue culture-treated membrane has a good affinity for the plant cell; thus, protoplasts can spread evenly and form a very thin layer.*There are more choices for membrane pore size, depending on the application.*It is very convenient to change or collect the solution without mechanically disturbing the protoplasts. This simple and effective silica sol-gel/alginate two-step immobilization of protoplasts in Transwell has great potential for applications in genetic transformation, metabolite production, and migration assays. PMID- 26150969 TI - A simple and versatile method for frequent 24 h blood sample collection in healthy older adults. AB - Repeated 24 h blood sampling, which is required for time series analyses of metabolites and/or hormones that show strong fluctuations in blood concentration over time, has a higher failure rate in older adults. We tailored existing venipuncture protocols toward use for 24 h blood sampling (sampling frequency of 10 min) in older adults. The following modifications were made: *Pre-sampling: evidence based risk assessment of older adults.*During sampling:*Ultrasound guided identification and characterisation of veins.*Use of 20-gauge arterial catheter with guide wire for venous access.*Measures to prevent and/or reduce unidirectional blood flow (fluid flow into but not out of the vein) included:*Use of hot water bottles to dilate veins.*Use of small gauge syringes, shortening of the extension line, and slowing of the blood withdrawal rate to reduce pressure on veins.*Stimulation of movement of the arm or retraction of the IV cannula to relieve mechanical flow obstruction.*Post-sampling: prevention of bruising and prolonged bleeding. PMID- 26150970 TI - Quick and reliable method for retina dissociation and separation of rod photoreceptor perikarya from adult mice. AB - A pure and abundant population of adult rod perikarya can be exploited in different studies concerning nuclear functions such as gene expression analyses which aim at elucidating the relationship between cell type and disease [1]. Sorting is based either on specific cell-surface markers or fluorescently labeled reporter proteins. Here, we describe a simple and reliable method for separation of rod photoreceptor perikarya without the use of staining procedures or transgenic mice. This method is limited, however, to sorting rod photoreceptors from adult mouse retina. Mature rods possess an inverted nuclear architecture which is determined by the optical functions of these nuclei [2]. The high backscatter of heterochromatin in the core of the nucleus can be used as a selection criterion for FAC-sorting by forward and sideward scatter. *The procedure for retina dissociation using the Papain Dissociation System (Wothington Biochemical Corporation) was optimized.*An easy to follow step-by step protocol for retina dissociation was devised.*Rod perikarya were FAC-sorted by forward and sideward scatter based solely on the high backscatter of heterochromatin in their nuclei. PMID- 26150971 TI - Development of a pyrosequencing assay for the typing of alphaherpesviruses. AB - Identification of herpesvirus in biological material is usually carried out by real-time PCR. With the aim to classify the strain of virus identified, real-time PCR must be often supported by time-consuming capillary electrophoresis sequencing analysis. Here we provide a protocol for the rapid and reliable identification of 5 closely related herpesviruses by PyroMark Q24 sequencing system. PyroMark performs DNA sequencing analysis using pyrosequencing, a technology based on the detection of released pyrophosphate during DNA elongation [1]. PyroMark is designed to detect changes in specified variable positions of the DNA. It can efficiently detect single nucleotide differences in sequences [2]. In the present paper we describe a protocol to pyrosequence a small polymorphic segment of the US8 gene. On the basis of the differences identified in the nucleotide sequence we could readily classify the herpesvirus as Bovine herpesvirus 1.1, Bovine herpesvirus 1.2, Bovine herpesvirus 5, Bubaline herpesvirus 1 or Caprine herpesvirus. The protocol set up offers several advantages with respect to the techniques commonly used: *it requires less than one working day to be carried;*it gives the possibility to analyze, at reasonable costs, up to 24 samples at a time; and*it allows to detect with great reliability and specificity strongly genetically correlated organisms like the herpesviruses named above. The procedure can be easily applied to other families of viruses, with opportune modifications. PMID- 26150972 TI - Rapid RNA analysis of individual Caenorhabditis elegans. AB - Traditional RNA extraction methods rely on the use of hazardous chemicals such as phenol, chloroform, guanidinium thiocyanate to disrupt cells and inactivate RNAse simultaneously. RNA isolation from Caenorhabditis elegans presents another challenge due to its tough cuticle, therefore several repeated freeze-thaw cycles may be needed to disrupt the cuticle before the cell contents are released. In addition, a large number of animals are required for successful RNA isolation. To overcome these issues, we have developed a simple and efficient method using proteinase K and a brief heat treatment to release RNA of quality suitable for quantitative PCR analysis.The benefits of the method are: *Faster and safer compared to conventional RNA extraction methods*Released RNA can be used directly for cDNA synthesis without purification*As little as a single worm is sufficient. PMID- 26150973 TI - Isolation of novel sequences targeting highly variable viral protein hemagglutinin. AB - Rapid evolution is a hallmark of the viral kingdom and a major concern for developing universal vaccines. The isolation of substantial numbers of viral sequence variants at highly variable viral protein domains remains a major challenge. We previously developed a combinatorial method for the isolation of novel sequences to cope with rapid viral variations at the G-H loop of Foot and Mouth Disease virus VP1 protein [1]. Here we present a modification of that method in its application in the randomization of the hemagglutinin gene from a H5N2 virus, namely: *removal of potentially stressful region which harbored a stretch of basic amino acids to increase the success rates of gene cloning, and to streamline the process of future engineering of novel viral variants.*clustered randomization in a full-length gene, as the positive rate for partial gene fragment libraries was extremely low before enrichment in the previous FMDV studies.*the use of fusion partner was avoided, which was used previously for protein expression, stabilization of clones and reduction of stresses on host cells.*the use of Poisson distribution is proposed to approximate sequencing output to achieve cost effectiveness. PMID- 26150974 TI - Indole-3-acetic acid (IAA) production trait, a useful screening to select endophytic and rhizosphere competent bacteria for rice growth promoting agents. AB - Plants select plant growth promoting rhizobacteria (PGPR) that are competitively fit to occupy compatible niches without causing pathological stress on them. However, when screening bacteria for plant growth promoting (PGP) agents, it is better to select bacteria for achieving the most promising isolates having suitable colonization and PGP traits. In most researches, it has been seen that following incubation, bacterial flora are taken at random from petri dishes for further study. However, this type of selection may remove some superior bacteria in terms of PGP traits and high colonization ability. Therefore, it is essential to study all the isolated bacteria in an economic way and select the best bacteria in terms of PGP traits and high colonization rate. A simple screening method to detect endophytic and rhizosphere bacteria, isolated from the plants in rotation with rice, for rice PGP agents based on a root colonization bioassay and a PGP trait is characterized. *Selected bacterial isolates based on their IAA producing trait have the potential for more PGP and colonization of rice plant.*IAA may be the first PGP trait for screening bacteria isolated from plant rotated with rice for rice PGP agents.*The screening procedure appears to be very effective and less time consuming. PMID- 26150975 TI - Efficient Voronoi volume estimation for DEM simulations of granular materials under confined conditions. AB - When the discrete element method (DEM) is used to simulate confined compression of granular materials, the need arises to estimate the void space surrounding each particle with Voronoi polyhedra. This entails recurring Voronoi tessellation with small changes in the geometry, resulting in a considerable computational overhead. To overcome this limitation, we propose a method with the following features:*A local determination of the polyhedron volume is used, which considerably simplifies implementation of the method.*A linear approximation of the polyhedron volume is utilised, with intermittent exact volume calculations when needed.*The method allows highly accurate volume estimates to be obtained at a considerably reduced computational cost. PMID- 26150976 TI - A method based on light scattering to estimate the concentration of virus particles without the need for virus particle standards. AB - Most often the determination of the concentration of virus particles is rendered difficult by the availability of proper standards. We have adapted a static light scattering based method for the quantification of virus particles (shown for poliovirus) without the need of virus particle standards. Instead, as standards, well-characterized polymeric nanoparticle solutions are used. The method is applicable for virus particles acting as Rayleigh scatterers, i.e., virus particles with equivalent diameters up to ca. 1/10th of the wavelength of the scattered monochromatic light (~70 nm diameter). Further limitations may arise if the refractive index of the virus is unavailable or cannot be calculated based on its composition, such as in case of enveloped viruses. The method is especially relevant for preparation of virus particle concentration standards and to vaccine formulations based on attenuated or inactivated virus particles where the classical plaque forming assays cannot be applied. The method consists of: *Measuring the intensity of the light scattered by viruses suspended in an aqueous solution.*Measuring the intensity of the light scattered by polymeric nanoparticles of known concentration and comparable size with the investigated virus particle.*The concentration of virus nanoparticles can be calculated based on the two measured scattered light intensities by knowing the refractive index of the dispersing solution, of the polymer and virus nanoparticles as well as their relative sphere equivalent diameters. PMID- 26150977 TI - Novel waste printed circuit board recycling process with molten salt. AB - The objective of the method was to prove the concept of a novel waste PCBs recycling process which uses inert, stable molten salts as the direct heat transfer fluid and, simultaneously, uses this molten salt to separate the metal products in either liquid (solder, zinc, tin, lead, etc.) or solid (copper, gold, steel, palladium, etc.) form at the operating temperatures of 450-470 degrees C. The PCB recovery reactor is essentially a U-shaped reactor with the molten salt providing a continuous fluid, allowing molten salt access from different depths for metal recovery. A laboratory scale batch reactor was constructed using 316L as suitable construction material. For safety reasons, the inert, stable LiCl-KCl molten salts were used as direct heat transfer fluid. Recovered materials were washed with hot water to remove residual salt before metal recovery assessment. The impact of this work was to show metal separation using molten salts in one single unit, by using this novel reactor methodology. *The reactor is a U-shaped reactor filled with a continuous liquid with a sloped bottom representing a novel reactor concept.*This method uses large PCB pieces instead of shredded PCBs as the reactor volume is 2.2 L.*The treated PCBs can be removed via leg B while the process is on-going. PMID- 26150978 TI - Improvement of isometric dorsiflexion protocol for assessment of tibialis anterior muscle strength. AB - It is important to accurately estimate the electromyogram (EMG)/force relationship of triceps surae (TS) muscle for detecting strength deficit of tibalis anterior (TA) muscle. In literature, the protocol for recording EMG and force of dorsiflexion have been described, and the necessity for immobilizing the ankle has been explained. However, there is a significant variability of the results among researchers even though they report the fixation of the ankle. We have determined that toe extension can cause significant variation in the dorsiflexion force and EMG of TS and this can occur despite following the current guidelines which require immobilizing the ankle. The results also show that there was a large increase in the variability of the force and the RMS of EMG of TS when the toes were not strapped compared with when they were strapped. Thus, with the current guidelines, where there are no instructions regarding the necessity of strapping the toes, the EMG/force relationship of TS could be incorrect and give an inaccurate assessment of the dorsiflexor TA strength. In summary, *Current methodology to estimate the dorsiflexor TA strength with respect to the TS activity, emphasizing on ankle immobilization is insufficient to prevent large variability in the measurements.*Toe extension during dorsiflexion was found to be one source of variability in estimating the TA strength.*It is recommended that guidelines for recording force and EMG from TA and TS muscles should require the strapping of the toes along with the need for immobilizing the ankle. PMID- 26150979 TI - Signal loss due to oligomerization in ELISA analysis of amyloid-beta can be recovered by a novel sample pre-treatment method. AB - According to the predominant theories, soluble amyloid-beta (Abeta) aggregates are the principal neurotoxic agents in Alzheimer's disease pathology, making them a popular target for the development of therapeutics and diagnostic markers. One of the most commonly used methods for determining the concentration of Abeta is ELISA. However, ELISA was developed for monomeric proteins and may be ill-suited for detecting aggregates. Therefore, we investigated the effect of aggregation on the ELISA measurement and developed a novel chemical pre-treatment method, designed to disaggregate Abeta peptides, to improve the ELISA measurement of the total Abeta concentration. Synthetic Abeta40 monomers, Abeta42 oligomers and biological samples from mice and humans were subjected to a chemical pre treatment protocol with: trifluoroacetic acid (TFA), formic acid (FA) or hexafluoroisopropanol (HFIP) prior to ELISA analysis. In our study we have shown that: *Abeta oligomerization leads to epitope masking and steric hindrance and results in an underestimation of the total Abeta content with ELISA.*Chemically pre-treating samples to disaggregate oligomers can (partially) recover the signal loss.*This novel sample pre-treatment method could provide a more accurate ELISA measurement of the total Abeta concentration in samples with a high oligomer content. PMID- 26150980 TI - Determination of collagen content within picrosirius red stained paraffin embedded tissue sections using fluorescence microscopy. AB - Picrosirius red (PSR) staining is a commonly used histological technique to visualize collagen in paraffin-embedded tissue sections. PSR stained collagen appears red in light microscopy. However it is largely unknown that PSR stained collagen also shows a red fluorescence, whereas live cells have a distinct green autofluorescence. Both emission patterns can be detected using standard filter sets as found in conventional fluorescence microscopes. Here we used digital image addition and subtraction to determine the relative area of the pure collagen and live cell content in heart tissue in a semi-automated process using standard software. This procedure, which considers empty spaces (holes) within the section, can be easily adapted to quantify the collagen and live cell areas in healthy or fibrotic tissues as aorta, lung, kidney or liver by semi-automated planimetry exemplified herein for infarcted heart tissue obtained from the mouse myocardial infarction model. *Use of conventional PSR stained paraffin-embedded tissue sections for fluorescence analysis.*PSR and autofluorescence images are used to calculate area of collagen and area of live cells in the tissue; empty spaces (holes) in tissue are considered.*High throughput analysis of collagen and live cell content in tissue for statistical purposes. PMID- 26150981 TI - 4S Peak Filling - baseline estimation by iterative mean suppression. AB - A novel baseline estimation procedure building on previously published works is presented. *The core of the estimation is an iterative spectrum suppression consisting of a moving window minimum replacement (adapted from Friedrichs [1]).*Four, easily understandable, parameters control placement of the baseline relative to the noise band around the signal (adapted from Eilers [2]) and the flexibility in different situations.*The method is especially suited for non linear baselines with local variations and for resolving peak clusters in qualitative analyses. PMID- 26150982 TI - Label-free method for anti-glucopeptide antibody detection in Multiple Sclerosis. AB - Surface plasmon resonance technique is particularly interesting in immunology because it has the potential to visualize label-free antigen-antibody interactions in real-time, thus enabling antibody detection and monitoring. Herein we release the guidelines for the correct use of a method to detect specific antibodies directly in Multiple Sclerosis patients' sera using a glucopeptide-based label-free biosensor. The protocol describes the strategy employed for the immobilization of glucopeptide antigen onto a gold sensor chip and the evaluation of the specific binding of serum antibodies to the immobilized antigen. *Label-free method for the real time screening of disease-specific antibodies within a few minutes;*The described protocol employs small quantities of glucopeptide antigen and blood serum samples saving method-cost;*Stability of the immobilized glucopeptide antigen guarantees the regeneration of the surface allowing re-use the immunosensor with high automated throughput. The antibodies detected using the described methodology can be evaluated as biomarkers of Multiple Sclerosis. The SPR detection system is able to characterize antibodies significantly different from those evaluated in the classical enzyme-linked immunosorbent assays (ELISA). PMID- 26150983 TI - Novel scripts for improved annotation and selection of variants from whole exome sequencing in cancer research. AB - Sequencing the exome is quickly becoming the preferred method for discovering disease-inducing mutations. While obtaining data sets is a straightforward procedure, the subsequent analysis and interpretation of the data is a limiting step for clinical applications. Thus, while the initial mutation and variant calling can be performed by a bioinformatician or trained researcher, the output from robust packages such as MuTect and GATK is not directly informative for the general life scientists. In attempt to obviate this problem we have created complementary Wolfram scripts, which enable easy downstream annotation and selection, presented here in the perspective of hematological relevance. It also provides the researcher with the opportunity to extend the analysis by having a full-fledged programming and analysis environment of Mathematica at hand. In brief, post-processing is performed by: *Mapping of germ line and somatic variants to coding regions, and defining variant sets within Mathematica.*Processing of variants in variant effect predictor.*Extended annotation, relevance scoring and defining focus areas through the provided functions. PMID- 26150984 TI - Development and optimization of a new culture media using extruded bean as nitrogen source. AB - The composition of a culture medium is one of the most important parameters to be analyzed in biotechnological processes with industrial purposes, because around 30-40% of the production costs were estimated to be accounted for the cost of the growth medium [1]. Since medium optimization using a one-factor-at-a-time approach is time-consuming, expensive, and often leads to misinterpretation of results, statistical experimental design has been applied to medium optimization for growth and metabolite production [2-5]. In this scenario, the use of mixture design to develop a culture medium containing a cheaper nitrogen source seems to be more appropriate and simple. In this sense, the focus of this work is to present a detailed description of the steps involved in the development of a optimized culture medium containing extruded bean as nitrogen source. *In a previous work we tested a development of new culture media based on the composition of YPD medium, aiming to reduce bioprocess costs as well as to improve the biomass production and heterologous expression.*The developed medium was tested for growth of Saccharomyces cerevisiae and Pichia pastoris (GS 115).*The use of culture media containing extruded bean as sole nitrogen source showed better biomass production and protein expression than those observed in the standard YPD medium. PMID- 26150985 TI - Improved internal control for molecular diagnosis assays. AB - The two principal determining steps in molecular diagnosis are the amplification and the identification steps. Accuracy of DNA amplification is primarily determined by the annealing sequence of the PCR primer to the analyte DNA. Accuracy for identification is determined either by the annealing region of a labelled probe for the real time PCR analysis, or the annealing of a sequencing primer for DNA sequencing analysis, that binds to the respective analyte (amplicon). Presently, housekeeping genes (Beta globin, GAPDH) are used in molecular diagnosis to verify that the PCR conditions are optimum, and are thus known as amplification controls [1-4]. Although these genes have been useful as amplification controls, they lack the true definition of an internal control because the primers and annealing conditions are not identical to the analyte being assayed. This may result in a false negative report [5]. The IC-Code platform technology described here provides a true internal control where the internal control and analyte share identical PCR primers annealing sequences for the amplification step and identical sequencing primer annealing sequence for the identification step. *The analyte and internal control have the same PCR and sequencing annealing sequences.*This method assures for little or no false negatives and false positives due to the method's design of using identical annealing conditions for the internal control and analyte, and by using DNA sequencing analysis for the identification step of the analyte, respectively.*This method also allows for a set lower limit of detection to be used by varying the amount of internal control used in the assay. PMID- 26150986 TI - A perfusion protocol for lizards, including a method for brain removal. AB - The goal of fixation is to rapidly and uniformly preserve tissue in a life-like state. Perfusion achieves optimal fixation by pumping fixative directly through an animal's circulatory system. Standard perfusion techniques were developed primarily for application in mammals, which are traditional neuroscience research models. Increasingly, other vertebrate groups are also being used in neuroscience. Following mammalian perfusion protocols for non-mammalian vertebrates often results in failed perfusions. Here, I present a modified perfusion protocol suitable for lizards. Though geared towards standard brain perfusion, this protocol is easily modified for the perfusion of other tissues and for various specialized histological techniques. *The two aortas of the lizard heart, emerging from a single ventricle, mean that care must be taken to place the perfusion needle in the correct aorta, unlike in mammals.*Only the head and neck perfuse - the visceral organs will not decolour, and the body may not twitch.*I also include a method for removing a lizard brain, which differs from mammals due to the incomplete and thicker skull of the lizard. PMID- 26150987 TI - Modification of a commercial DNA extraction kit for safe and rapid recovery of DNA and RNA simultaneously from soil, without the use of harmful solvents. AB - An optimized method, based on the coupling of two commercial kits, is described for the extraction of soil nucleic acids, with simultaneous extraction and purification of DNA and RNA following a cascade scheme and avoiding the use of harmful solvents. The protocol canmonitor the variations in the recovery yield of DNA and RNA from soils of various types.The quantitative version of the protocol was obtained by testing the starting soil quantity, the grinding parameters and the final elution volumes, in order to avoid saturation of both kits. *A first soil-crushing step in liquid nitrogen could be added for the assessment of fungal parameters.*The protocol was efficienton different tropical soils, including Andosol, while their high contents of clays, including poorly crystalline clays, and Fe and Al oxides usually make the nucleic acid extraction more difficult.*The RNA recovery yield from the previous tropical soils appeared to correlate better to soil respiration than DNA, which is positively influenced by soil clay content. PMID- 26150988 TI - Building a symbolic computer algebra toolbox to compute 2D Fourier transforms in polar coordinates. AB - The development of a symbolic computer algebra toolbox for the computation of two dimensional (2D) Fourier transforms in polar coordinates is presented. Multidimensional Fourier transforms are widely used in image processing, tomographic reconstructions and in fact any application that requires a multidimensional convolution. By examining a function in the frequency domain, additional information and insights may be obtained. The advantages of our method include: *The implementation of the 2D Fourier transform in polar coordinates within the toolbox via the combination of two significantly simpler transforms.*The modular approach along with the idea of lookup tables implemented help avoid the issue of indeterminate results which may occur when attempting to directly evaluate the transform.*The concept also helps prevent unnecessary computation of already known transforms thereby saving memory and processing time. PMID- 26150989 TI - Baking sunflower hulls within an aluminum envelope in a common laboratory oven yields charcoal. AB - Charcoals have been widely used by scientist to research the removal of contaminants from water and air. One key feature of charcoal is that it keeps macropores from the parent material - though anisotropically contracted - and can even develop meso- and micropores. However, the controlled thermochemical conversion of biomass into charcoal at laboratory scale normally requires special setups which involve either vacuum or inert gas. Those setups may not be affordable in research groups or educational institutions where the research of charcoals would be highly welcome. In this work, I propose a simple and effective method to steer the thermochemical process that converts sunflower hulls (SFH) into charcoal with basic laboratory resources. The carbonization method: *Place SFH in an airtight aluminum envelope.*Thermally treat SFH within the envelope in a common laboratory oven.*Open the envelope to obtain the carbonized sunflower hulls. PMID- 26150990 TI - Multielectrode Teflon electrochemical nanocatalyst investigation system. AB - The most common approach in the search for the optimal low temperature fuel cell catalyst remains "trial and error". Therefore, large numbers of different potential catalytic materials need to be screened. The well-established and most commonly used method for testing catalytic electrochemical activity under well defined hydrodynamics is still thin film rotating disc electrode (TF-RDE). Typically this method is very time consuming and is subjected to impurity problems. In order to avoid these issues a new multielectrode electrochemical cell design is presented, where 8 different electrocatalysts can be measured simultaneously at identical conditions. The major advantages over TF-RDE method are: *Faster catalyst screening times.*Greater impurity tolerance.*The option of internal standard. PMID- 26150991 TI - Determination of phosphate in soil extracts in the field: A green chemistry enzymatic method. AB - Measurement of ortho-phosphate in soil extracts usually involves sending dried samples of soil to a laboratory for analysis and waiting several weeks for the results. Phosphate determination methods often involve use of strong acids, heavy metals, and organic dyes. To overcome limitations of this approach, we have developed a phosphate determination method which can be carried out in the field to obtain results on the spot. This new method uses: *Small volumes.*An enzymatic reaction.*Green chemistry. First, the soil sample is extracted with deionized water and filtered. Next, an aliquot of the soil extract (0.5 mL) is transferred to a disposable cuvette, containing 0.5 mL of reaction mixture [200 mM HEPES, pH 7.6, 20 mM MgCl2, with 80 nmol 2-amino-6-mercapto-7-methylpurine ribonucleoside (MESG) and 1 unit of recombinant purine nucleoside phosphorylase (PNP; EC 2.4.2.1)], mixed, and incubated for 10 min at field temperature. Absorbance of the completed reaction is measured at 360 nm in open-source, portable photometer linked by bluetooth to a smartphone. The phosphate and phosphorus content of the soil is determined by comparison of its absorbance at 360 nm to a previously prepared standard phosphate curve, which is stored in the smartphone app. PMID- 26150992 TI - A methodology for identification and control of electro-mechanical actuators. AB - Mechatronic systems are fully-integrated engineering systems that are composed of mechanical, electronic, and computer control sub-systems. These integrated systems use electro-mechanical actuators to cause the required motion. Therefore, the design of appropriate controllers for these actuators are an essential step in mechatronic system design. In this paper, a three-stage methodology for real time identification and control of electro-mechanical actuator plants is presented, tested, and validated. First, identification models are constructed from experimental data to approximate the plants' response. Second, the identified model is used in a simulation environment for the purpose of designing a suitable controller. Finally, the designed controller is applied and tested on the real plant through Hardware-in-the-Loop (HIL) environment. The described three-stage methodology provides the following practical contributions: *Establishes an easy-to-follow methodology for controller design of electro mechanical actuators.*Combines off-line and on-line controller design for practical performance.*Modifies the HIL concept by using physical plants with computer control (rather than virtual plants with physical controllers). Simulated and experimental results for two case studies, induction motor and vehicle drive system, are presented in order to validate the proposed methodology. These results showed that electromechanical actuators can be identified and controlled using an easy-to-duplicate and flexible procedure. PMID- 26150993 TI - Sleep scoring made easy-Semi-automated sleep analysis software and manual rescoring tools for basic sleep research in mice. AB - Studying sleep behavior in animal models demands clear separation of vigilance states. Pure manual scoring is time-consuming and commercial scoring software is costly. We present a LabVIEW-based, semi-automated scoring routine using recorded EEG and EMG signals. This scoring routine is *designed to reliably assign the vigilance/sleep states wakefulness (WAKE), non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) to defined EEG/EMG episodes.*straightforward to use even for beginners in the field of sleep research.*freely available upon request. Chronic recordings from mice were used to design and evaluate the scoring routine consisting of an artifact-removal, a scoring- and a rescoring routine. The scoring routine processes EMG and different EEG frequency bands. Amplitude-based thresholds for EEG and EMG parameters trigger a decision tree assigning each EEG episode to a defined vigilance/sleep state automatically. Using the rescoring routine individual episodes or particular state transitions can be re-evaluated manually. High agreements between auto-scored and manual sleep scoring could be shown for experienced scorers and for beginners quickly and reliably. With small modifications to the software, it can be easily adapted for sleep analysis in other animal models. PMID- 26150994 TI - Simultaneous detection and quantification of six equine cytokines in plasma using a fluorescent microsphere immunoassay (FMIA). AB - Cytokines are cell signalling proteins that mediate a number of different physiological responses. They are also biomarkers for inflammatory conditions and potential diagnostic references for diseases. Until recently, simultaneous quantification of cytokine profiles had not been possible. Now however, fluorescent microsphere immunoassays (FMIA) are able to measure multiple cytokines in a single sample. The following pro-inflammatory and anti inflammatory cytokines were quantified in equine plasma and serum samples: interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha. *The objective of this study was to quantify six equine cytokines simultaneously using the BioPlex((r)) 200 system in equine EDTA-plasma and serum.*It demonstrates an increased number of detectable cytokines over published studies.*This technology has the advantage of reduced sample volume and assay time compared to traditional sandwich ELISAs. PMID- 26150995 TI - Improved method for enumerating sulfate-reducing bacteria using optical density. AB - The photometric determination of bacterial concentration can be affected by secondary scattering and other interferences. The conventional growth medium for sulfate-reducing bacteria (SRB) has iron that precipitates as iron sulfides, a dark precipitate which is useful to indicate bacterial activity. However, iron hydroxides also precipitate at high pH values and the presence of these precipitates interferes considerably in the optical density of the solution affecting estimates of the cell population thus seriously limiting the use of the conventional method. In this method a modification of the current method improves the measurement of the optical density of a solution with SRB cells. *The method consists of an acidification with hydrochloric acid of a sample of a mixed culture of SRB enriched from the produced water from oil fields to pH below 2.*The results show that the relationship between the bacterial dry mass and absorbance is exponential in the observed range. It was observed a large slope in the linearized fit equation, and the acidified solution does not change the integrity of the SRB cells after the treatment.*The results of the kinetic experiments, including the bacterial growth time evolution, demonstrate the applicability of the method. PMID- 26150996 TI - An improved 96-well turbidity assay for T4 lysozyme activity. AB - T4 lysozyme (T4L) is an important model system for investigating the relationship between protein structure and function. Despite being extensively studied, a reliable, quantitative activity assay for T4L has not been developed. Here, we present an improved T4L turbidity assay as well as an affinity-based T4L expression and purification protocol. This assay is designed for 96-well format and utilizes conditions amenable for both T4L and other lysozymes. This protocol enables easy, efficient, and quantitative characterization of T4L variants and allows comparison between different lysozymes. Our method: *Is applicable for all lysozymes, with enhanced sensitivity for T4 lysozyme compared to other 96-well plate turbidity assays;*Utilizes standardized conditions for comparing T4 lysozyme variants and other lysozymes; and*Incorporates a simplified expression and purification protocol for T4 lysozyme. PMID- 26150997 TI - Robust optical fiber patch-cords for in vivo optogenetic experiments in rats. AB - In vivo optogenetic experiments commonly employ long lengths of optical fiber to connect the light source (commonly a laser) to the optical fiber implants in the brain. Commercially available patch cords are expensive and break easily. Researchers have developed methods to build these cables in house for in vivo experiments with rodents [1-4]. However, the half-life of those patch cords is greatly reduced when they are used with behaving rats, which are strong enough to break the delicate cable tip and to bite through the optical fiber and furcation tubing. Based on [3] we have strengthened the patch-cord tip that connects to the optical implant, and we have incorporated multiple layers of shielding to produce more robust and resistant cladding. Here, we illustrate how to build these patch cords with FC or M3 connectors. However, the design can be adapted for use with other common optical-fiber connectors. We have saved time and money by using this design in our optical self-stimulation experiments with rats, which are commonly several months long and last four to eleven hours per session. The main advantages are: *Long half-life.*Resistant to moderate rodent bites.*Suitable for long in vivo optogenetic experiments with large rodents. PMID- 26150998 TI - AutoTag and AutoSnap: Standardized, semi-automatic capture of regions of interest from whole slide images. AB - Tumor angiogenesis is measured by counting microvessels in tissue sections at high power magnification as a potential prognostic or predictive biomarker. Until now, regions of interest (ROIs) were selected by manual operations within a tumor by using a systematic uniform random sampling (SURS) approach. Although SURS is the most reliable sampling method, it implies a high workload. However, SURS can be semi-automated and in this way contribute to the development of a validated quantification method for microvessel counting in the clinical setting. Here, we report a method to use semi-automated SURS for microvessel counting: *Whole slide imaging with Pannoramic SCAN (3DHISTECH)*Computer-assisted sampling in Pannoramic Viewer (3DHISTECH) extended by two self-written AutoHotkey applications (AutoTag and AutoSnap)*The use of digital grids in Photoshop((r)) and Bridge((r)) (Adobe Systems) This rapid procedure allows traceability essential for high throughput protein analysis of immunohistochemically stained tissue. PMID- 26150999 TI - A novel method for extraction of a proteinous coagulant from Plantago ovata seeds for water treatment purposes. AB - Several chemicals have been applied in the process of coagulant extraction from herbal seeds, and the best extraction has been obtained in the presence of KCl or NaNO3[1-3], and NaCl [4]. However, the main challenge posed to these methods of coagulant extraction is their relatively low efficiency for water treatment purposes and the formation of dissolved organic matter during the treatment process. In these methods the salts, which have a one-valance metal (Na(+) and K(+)), are deposited in the internal structure and the pore of the coagulant, and may be useful for the coagulation/flocculation process. In this research, we found that modified methods produced more dense protein. Therefore, the modified procedure was better than the older one for removal of turbidity and harness from the contaminated water. Here we describe a method where: *According to the Hardy Schulze rule, we applied the Fe(3+) ions instead of Na(+) and K(+) for the extraction of protein from Plantago ovata seeds.*The method was narrowed to extract protein by ethanol (defatting) and ammonium acetate and CM-Sepharose (protein extraction).*Two consecutive elutriations of crude extract was directly performed using 0.025-M FeCl3 and 0.05-M FeCl3 according to the basis of the ion exchange processes. PMID- 26151000 TI - Modeling mixed boundary conditions in a Hilbert space with the complex variable boundary element method (CVBEM). AB - The Laplace equation that results from specifying either the normal or tangential force equilibrium equation in terms of the warping functions or its conjugate can be modeled as a complex variable boundary element method or CVBEM mixed boundary problem. The CVBEM is a well-known numerical technique that can provide solutions to potential value problems in two or more dimensions by the use of an approximation function that is derived from the Cauchy Integral in complex analysis. This paper highlights three customizations to the technique.*A least squares approach to modeling the complex-valued approximation function will be compared and analyzed to determine if modeling error on the boundary can be reduced without the need to find and evaluated additional linearly independent complex functions.*The nodal point locations will be moved outside the problem domain.*Contour and streamline plots representing the warping function and its complementary conjugate are generated simultaneously from the complex-valued approximating function. PMID- 26151002 TI - Welcome readers. PMID- 26151001 TI - Cellular imaging of endosome entrapped small gold nanoparticles. AB - Small gold nanoparticles (sAuNPs, <10 nm in a core diameter) have been used for drug delivery and cancer therapy due to their high payload to carrier ratio. Information about the amount and location of sAuNPs in cells and tissues is critical to many applications. However, the current detection method (i.e., transmission electron microscopy) for such sAuNPs is limited due to the extensive sample preparation and the limited field of view. Here we use confocal laser scanning microscopy to provide endosome-entrapped sAuNP distributions and to quantify particle uptake into cells. The quantitative capabilities of the system were confirmed by inductively coupled plasma-mass spectrometry, with an observed linear relation between scattering intensity and the initial cellular uptake of sAuNPs using 4 nm and 6 nm core particles. The summary of the method is: *This non-invasive imaging strategy provides a tool for label-free real-time tracking and quantification of sAuNPs using a commercially available confocal laser scanning microscope.*Scattering intensity depends on particle size.*The linear relation established between scattering intensity and uptaken gold amount enables simultaneous quantitative assessment through simple image analysis. PMID- 26151003 TI - Nutraceuticals for geriatrics. AB - Geriatrics is a medical practice that addresses the complex needs of older patients and emphasizes maintaining functional independence even in the presence of chronic disease. Treatment of geriatric patients requires a different strategy and is very complex. Geriatric medicines aim to promote health by preventing and treating diseases and disabilities in older adults. Development of effective dietary interventions for promoting healthy aging is an active but challenging area of research because aging is associated with an increased risk of chronic disease, disability, and death. Aging populations are a global phenomenon. The most widespread conditions affecting older people are hypertension, congestive heart failure, dementia, osteoporosis, breathing problems, cataract, and diabetes to name a few. Decreased immunity is also partially responsible for the increased morbidity and mortality resulting from infectious agents in the elderly. Nutritional status is one of the chief variables that explains differences in both the incidence and pathology of infection. Elderly people are at increased risk for micronutrient deficiencies due to a variety of factors including social, physical, economic, and emotional obstacles to eating. Thus there is an urgent need to shift priorities to increase our attention on ways to prevent chronic illnesses associated with aging. Individually, people must put increased efforts into establishing healthy lifestyle practices, including consuming a more healthful diet. The present review thus focuses on the phytochemicals of nutraceutical importance for the geriatric population. PMID- 26151004 TI - Effects of green tea on Escherichia coli as a uropathogen. AB - Escherichia coli is the most common cause of urinary tract infections. The development of antibiotic resistance in E. coli is an important problem. Finding alternative antimicrobial agents from plant extracts has received growing interest. Camellia sinensis is a safe, nontoxic, cheap beverage that has been reported to have antimicrobial effects against various pathogenic bacteria including E. coli. Polyphenolic components of green tea ( lu cha) have antibacterial activity. Catechins also have synergistic effect with antibiotics such as chloramphenicol, amoxicillin, sulfamethoxazole, azithromycin, levofloxacin, gentamycin, methicillin, naldixic acid, and, especially ciprofloxacin. In this review, all experimental studies that evaluated the effect of green tea on E. coli were collected. Data from in vitro studies on the antimicrobial effects of green tea are promising, but human data are currently lacking. In vivo studies on antibacterial effects of green tea and evaluating the efficacy of its catechins in the treatment of urinary tract infection are needed. PMID- 26151005 TI - Evaluation of biological properties and clinical effectiveness of Aloe vera: A systematic review. AB - Aloe vera ( lu hui) is well known for its considerable medicinal properties. This plant is one of the richest natural sources of health for human beings coming. The chemistry of the plant has revealed the presence of more than 200 different biologically active substances. Many biological properties associated with Aloe species are contributed by inner gel of the leaves. Most research has been centralized on the biological activities of the various species of Aloe, which include antibacterial and antimicrobial activities of the nonvolatile constituents of the leaf gel. Aloe species are widely distributed in the African and the eastern European continents, and are spread almost throughout the world. The genus Aloe has more than 400 species but few, such as A. vera, Aloe ferox, and Aloe arborescens, are globally used for trade. A. vera has various medicinal properties such as antitumor, antiarthritic, antirheumatoid, anticancer, and antidiabetic properties. In addition, A. vera has also been promoted for constipation, gastrointestinal disorders, and for immune system deficiencies. However, not much convincing information is available on properties of the gel. The present review focuses on the detailed composition of Aloe gel, its various phytocomponents having various biological properties that help to improve health and prevent disease conditions. PMID- 26151006 TI - Evaluation of anxiolytic potency of essential oil and S-(+)-linalool from Cinnamomum osmophloeum ct. linalool leaves in mice. AB - Cinnamomum osmophloeum ct. linalool ( tu rou gui) is one chemotype of the indigenous cinnamons in Taiwan. This study examined the anxiolytic potency of leaf essential oil (LEO) from C. osmophloeum ct. linalool and its main constituent on 4-week ICR mice using an open field test (OFT), a light-dark test (LDT) and an elevated plus maze test (EPT). After oral administration of corn oil, LEO (250 mg/kg and 500 mg/kg), S-(+)-linalool (500 mg/kg), R-(-)-linalool (500 mg/kg), and trazodone hydrochloride (75 mg/kg) for 14 days, the anxiolytic effects on mice behavior were evaluated. The results showed that LEO from C. osmophloeum ct. linalool leaves and S-(+)-linalool can significantly increase the time mice remained in the center area of the OFT, the illuminated area of the LDT and the open arms of the EPT without any side effects affecting motor activity, indicating excellent anxiolytic responses. Furthermore, results from the measurements of monoamines in mice brain revealed decreases in serotonin, dopamine, and norepinephrine, which are consistent with their anxiolytic effects in animal models. The findings obtained suggest that LEO from C. osmophloeum ct. linalool and its major compound, S-(+)-linalool, possess anxiolytic properties without any side effects and thus support their potential use in treatment of anxiety disorders. PMID- 26151007 TI - Anticancer activity of Aristolochia ringens Vahl. (Aristolochiaceae). AB - Cancer is a leading cause of death worldwide and sustained focus is on the discovery and development of newer and better tolerated anticancer drugs especially from plants. The sulforhodamine B (SRB) in vitro cytotoxicity assay, sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used to investigate the anticancer activity of root extracts of Aristolochia ringens Vahl. (Aristolochiaceae; ma dou ling). AR-A001 (IC50 values of 20 MUg/mL, 22 MUg/mL, 3 MUg/mL, and 24 MUg/mL for A549, HCT-116, PC3, and THP 1 cell lines, respectively), and AR-A004 (IC50 values of 26 MUg/mL, 19.5 MUg/mL, 12 MUg/mL, 28 MUg/mL, 30 MUg/mL, and 22 MUg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1, respectively), were observed to be significantly active in vitro. Potency was highest with AR-A001 and AR-A004 for PC3 with IC50 values of 3 MUg/mL and 12 MUg/mL, respectively. AR-A001 and AR-A004 produced significant (p < 0.05-0.001) dose-dependent inhibition of tumor growth in the S-180 ascites model with peak effects produced at the highest dose of 120 mg/kg. Inhibition values were 79.51% and 89.98% for AR-A001 and AR-A004, respectively. In the S-180 solid tumor model, the inhibition of tumor growth was 29.45% and 50.50% for AR-A001 (120 mg/kg) and AR-A004 (110 mg/kg), respectively, compared to 50.18% for 5 fluorouracil (5-FU; 20 mg/kg). AR-A001 and AR-A004 were also significantly active in the leukemia model with 211.11% and 155.56% increase in mean survival time (MST) compared to a value of 211.11% for 5-FU. In conclusion, the ethanolic (AR A001) and dichloromethane:methanol (AR-A004) root extracts of AR possess significant anticancer activities in vitro and in vivo. PMID- 26151008 TI - Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata). AB - Andrographolide is a major bioactive secondary plant metabolite isolated Andrographis paniculata (Burm. F.) Wall. Ex. Nees. ( chuan xin lian), a well known traditionally used medicinal herb. The aim of the study was to pharmacologically evaluate the beneficial effect of andrographolide on stress induced thermoregulatory and other physiological responses in mice. A stress induced hyperthermia test was conducted in mice. The test agents were orally administered once daily for 11 consecutive days, and treatment effects on body weight changes, basal rectal temperature, and foot-shock-triggered hyperthermic responses were quantified on Day 1, Day 5, Day 7, and Day 10 of the experiments. Pentobarbital-induced hypnosis was quantified on the 11(th) day of treatment. Observations made during a pilot dose finding experiment revealed that, like A. paniculata extracts, pure andrographolide also possess adaptogenic properties. Observed dose-dependent efficacies of 3 mg/kg/d, 10 mg/kg/d, and 30 mg/kg/d andrographolide in the pilot experiment were reconfirmed by conducting two further analogous experiments using separate groups of either male or female mice. In these confirmatory experiments, efficacies of andrographolide were compared with that of 5 mg/kg/d oral doses of the standard anxiolytic diazepam. Significantly reduced body weights and elevated core temperatures of the three vehicle-treated control groups observed on the 5(th) day and subsequent observational days were completely absent even in the groups treated with the lowest andrographolide dose (3 mg/kg/d) or diazepam (5 mg/kg/d). Benzodiazepine like potentiation of pentobarbital hypnosis was observed in andrographolide treated animals. These observations reveal that andrographolide is functionally a diazepam-like desensitizer of biological mechanisms, and processes involved in stress trigger thermoregulatory and other physiological responses. PMID- 26151009 TI - Antioxidant effects of 14 Chinese traditional medicinal herbs against human low density lipoprotein oxidation. AB - The relationship between the antioxidant activities and inhibitory effect of 14 Chinese medicinal herbs against oxidized low-density lipoprotein (LDL) formation was evaluated. Prolongation of the lag phase of LDL oxidation depended on the concentration of the herbs. The concentration of each herb that was able to prolong the lag time by about two-fold was calculated and expressed as doubling time concentration. The lower the doubling-time concentration, the stronger the inhibitory effect exhibited toward LDL oxidation. Among them, Chrysanthemi Flos (Chrysanthemum morifolium ramat; gan ju hua), Crataegi Fructus (Crataegus pinnatifida Bge. var. major N.E.Br.; shan zha), and Roselle (Hibiscus sabdariffa Linn.; luo shen) showed significant inhibitory effects. Correlation coefficients between doubling-time concentration and radical-scavenging activities were high; the total phenolic content was also high. In conclusion, phenolic compounds contributed not only to antioxidant activities, but also to the inhibitory effect against LDL oxidation. Chrysanthemi Flos, Crataegi Fructus, and H. sabdariffa, with lower doubling-time concentrations, could be potent phytochemical agents to reduce LDL oxidation and prevent the progression of atherosclerosis. PMID- 26151010 TI - Polysaccharide gel coating of the leaves of Brasenia schreberi lowers plasma cholesterol in hamsters. AB - Brasenia schreberi ( chun cai) is an invasive aquatic weed found in the USA, but the plant has economic value in Asia where it is cultivated for food. The young leaves of B. schreberi are coated with gelatinous water-insoluble mucilage. This mucilage is a polysaccharide composed of galactose, mannose, fucose, and other monosaccharides. Because some carbohydrate gels are hypocholesterolemic, we evaluated their cholesterol-lowering properties in male hamsters fed hypercholesterolemic diets containing 2% gel coat from B. schreberi (GEL), or 1% cholestyramine (CA), or 5% hydroxypropyl methylcellulose (HPMC), and compared them to 5% microcrystalline cellulose (control) for 3 weeks. We found that very low-density lipoprotein-, low-density lipoprotein-, and total-cholesterol concentrations in plasma were significantly lowered by GEL, CA, and HPMC compared to control. High-density lipoprotein-cholesterol concentration was lowered by CA and HPMC. Body weights and abdominal adipose tissue weight of GEL and control group animals were greater than those of the CA and HPMC groups. Fecal lipid excretion was greater in the CA and HPMC groups than in the control group. Expression of hepatic CYP51 and CYP7A1 mRNA was upregulated by CA, HPMC, and GEL, indicating increased hepatic cholesterol and bile acid synthesis. Expression of low-density lipoprotein receptor mRNA was upregulated by all treatments. These results suggest that modulation of hepatic expression of cholesterol and bile acid metabolism-regulated genes contributes to the cholesterol-lowering effects of GEL. PMID- 26151011 TI - Opportunities for traditional Chinese medicine to address unmet challenges in modern healthcare. PMID- 26151012 TI - Can naturopathy provide answers to the escalating health care costs in India? AB - There are substantial areas of overlap between naturopathy and public health, which include a focus on health rather than disease, a preventive approach, and an emphasis on health promotion and health education. Public health can look to naturopathy for answers to the emergence of chronic disease through natural therapies, many of which can take the role of primordial and primary prevention of several diseases. Some selected naturopathic therapies include nutrition, hydrotherapy, fasting therapy, yoga, behavioral therapy, and health promotion. We must reorient our focus on prevention and wellness to make a true impact on escalating health care costs. With the National Health Policy in India emphasizing the need for integrating the Indian Systems of Medicines with modern medicine, now is the right time for naturopathy and public health to come together to provide a holistic health care system. PMID- 26151013 TI - Cinnamon from the selection of traditional applications to its novel effects on the inhibition of angiogenesis in cancer cells and prevention of Alzheimer's disease, and a series of functions such as antioxidant, anticholesterol, antidiabetes, antibacterial, antifungal, nematicidal, acaracidal, and repellent activities. AB - The purpose of this article is to use search engines such as PubMed and Scifinder to locate scholarly articles and reports pertaining to Cinnamon ( rou gui), its novel effects, preparation, analysis, and use in the prevention and treatment of serious illnesses, such as diabetes, cardiovascular diseases, Alzheimer's disease, and cancer. Cinnamon has been used traditionally in food preparations and as an herbal medicine to treat a variety of ailments and their symptoms. Cinnamon is known to have antioxidant, antibacterial, anti-inflammatory, and other therapeutic properties. New studies reaffirm the importance of cinnamon as a spice but also suggest that it may be a natural remedy to treat serious diseases such as type 2 diabetes, chronic digestion problems, cardiovascular diseases, and even cancer and Alzheimer's disease. This article presents a comprehensive analysis of the botanical, chemical, and pharmacological aspects of cinnamon. PMID- 26151014 TI - Pharmacological treatment of catarrh in Iranian traditional medicine. AB - Catarrh is a condition that is carefully explained in Iranian traditional medicine. Medieval Iranian physicians used some medicinal plants in the treatment of the catarrh. Some of these substances are used in treatment today, although still more of these materials can be used in modern medicine. In this study we searched known sources of Iranian traditional medicine and collected the ideas of former great scholars and physicians about medicinal plants that are used for treatment of catarrh. Then we searched PubMed, Google Scholar, Scopus, and Web of Science databases and found 10 medicinal herbs that have the ability to treat catarrh. Plants discussed in this study are consistent with new research and can be used in modern treatments. According to rising bacterial resistance to antibiotics and complications of antibiotic and anti-inflammatory drugs, it seems that the various components of the medicinal herbs can be beneficial in producing new drugs. Also it is hoped that more investigations on medicinal plants will be conducted in the future treatment of catarrh and other diseases related to it. PMID- 26151015 TI - Scorpion sting prevention and treatment in ancient Iran. AB - Due to the medical and therapeutic importance of scorpions in Iranian traditional medicine, this review was conducted on the treatment of scorpion sting as performed by traditional healers in order to realize complications, clinical manifestations, diversities, and deficiencies in the prevention, control, and treatment as mentioned in the pertained literatures. This study tried to make known and investigate attitudes of the Iranian national and traditional medicine towards controlling these venomous animals. Keywords and articles were searched through relevant sites on the Internet. We investigated different journals and references for the Iranian traditional medicine. Based on the articles and books found, we tried to find suitable solutions to problems from the viewpoint of traditional medicine. Scorpion sting dates back to ancient Iran and has been widely reflected in the resources of Iranian traditional medicine. The traditional medicine offers various guidelines that can be beneficial in this respect. New attitude towards scorpion sting with regard to traditional medicine resources can enhance control and prevention of scorpion stings. Consequently, this attitude leads authorities and researchers to a decreased level of scorpion stings or related consequences. PMID- 26151016 TI - Crocus sativus L. (saffron) for cancer chemoprevention: A mini review. AB - Cancer is one of the most feared diseases globally and there has been a sustained rise in its incidence in both developing and developed countries. Despite the growing therapeutic options for patients with cancer, their efficacy is time limited and non-curative. Hence to overcome these drawbacks, an incessant screening for superior and safer drugs has been ongoing for numerous decades, resulting in the detection of anti-cancer properties of several phytochemicals. Chemoprevention using readily available natural substances from vegetables, fruits, herbs and spices is one of the significantly important approaches for cancer prevention in the present era. Among the spices, Crocus sativus L. (saffron; fan hong hua) has generated interest because pharmacological experiments have established numerous beneficial properties including radical scavenging, anti-mutagenic and immuno-modulating effects. The more powerful components of saffron are crocin, crocetin and safranal. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities of saffron and its main ingredients. This review provides a brief insight into the anticancer properties of saffron and its components. PMID- 26151017 TI - Physical and physiological effectiveness of an overall health care program for middle-aged Japanese women with mild obesity: A pilot study. AB - This study aimed to verify the effectiveness of an overall health care program (OHCP) for middle-aged Japanese women through assessing physical and physiological changes. The OHCP consisted of diet modification with natural alternative foods, walking and stretching exercises, and body massage and cupping treatments. Sixty-seven participants were assigned to one of three groups during a 3-year study period (2011-2013). The OHCP was performed for 3 months in each year. After the OHCP, most participants had significant decreases in the blood levels of triglycerides, low-density lipoprotein cholesterol, total cholesterol, alkaline phosphatase, gamma-glutamyl transferase, and cholinesterase; body weight; body fat percentage; and body-mass index. The oxidative stress markers varied among the study years; however, a significant decrease in blood reactive oxygen-derived metabolites and a significant increase in the relative antioxidative potential were observed in 2013. In 2013, participants who were randomly selected for autonomic nervous activity measurements immediately before and after body massage and cupping treatments showed a significant predominance in parasympathetic nervous activity after the treatments. These results indicate that the OHCP in the present study is an effective and prompt method as a complementary treatment to improve the pre-obese or mild obese status without any noticeable physiological stress in most middle-aged women. However, because of the limitations of this study, the findings of this study need to be confirmed. PMID- 26151018 TI - In vitro and in vivo antileishmanial effects of aloe-emodin on Leishmania major. AB - Cutaneous leishmaniasis is a common parasitic disease that is endemic in some parts of Iran. The drugs of choice used for leishmaniasis therapy are associated with a risk of recurrence and serious adverse effects. Therefore, finding a safe and effective treatment is of great importance. In the present study, the effect of aloe-emodin on the growth of Leishmania major amastigotes was evaluated under in vitro conditions. In addition, the efficacy of a topical of aloe-emodin ointment was investigated in BALB/c mice with cutaneous leishmanial ulcers. Different concentrations (40 MUg/mL, 80 MUg/mL, 120 MUg/mL, and 160 MUg/mL) of aloe-emodin were tested on Leishmania amastigotes twice: 24 hours and 48 hours. The induced apoptosis and necrotic effects of two concentrations (40 MUg/mL and 120 MUg/mL) of aloe-emodin on promastigotes were investigated by flow cytometry. Under the in vivo condition, aloe-emodin ointment efficacy was evaluated at two concentrations (i.e., 0.1% and 1%). Serum indicator factors of the test and control groups were tested to evaluate the toxic effects of this compound on the liver and kidney. Results showed that aloe-emodin inhibited the growth of Leishmania amastigotes and induced apoptosis in promastigotes. Topical application of aloe-emodin ointment likewise reduced the ulcer size. No significant differences in biochemical analysis were observed between the control and treated groups. In conclusion, aloe-emodin showed antileishmanial effects under in vitro and in vivo conditions and may be used in clinical trials. PMID- 26151019 TI - The influence of cigarette smoking on blood and salivary super oxide dismutase enzyme levels among smokers and nonsmokers-A cross sectional study. AB - To determine the influence of smoking on blood and salivary superoxide dismutase enzyme levels among smokers, and to demonstrate the significant alterations in the levels of superoxide dismutase in association with patient age, periodontal disease status, smoking duration, and smoking frequency. This study also aimed to evaluate the use of saliva as a biological fluid for disease diagnosis. Ninety males aged 25-56 years were selected and included 30 smokers, 30 nonsmokers with chronic periodontitis, and 30 healthy controls. Clinical parameters such as the gingival index, pocket depth, and clinical attachment loss were recorded. Blood and saliva samples were collected and superoxide dismutase enzyme levels were analyzed using spectrophotometric assay. Superoxide dismutase enzyme levels in the blood and saliva were significantly higher in smokers than in nonsmokers and the controls (p < 0.05). A significant correlation existed between superoxide dismutase levels and clinical parameters. There was also a significant positive correlation between blood and salivary superoxide dismutase levels among the three groups. Systemic and local antioxidant status is affected by periodontal disease and by the impact of smoking. The increased blood and salivary superoxide dismutase enzyme levels in smokers may be an adaptive defense mechanism to counteract the increased reactive oxygen species production induced by smoking. This study emphasizes the importance of saliva as an easy noninvasive tool in diagnosing patients who are more prone to precancerous lesions and conditions, and its importance in patient education and motivation programs for smoking cessation. PMID- 26151020 TI - Modulatory potentials of the aqueous stem bark extract of Mangifera indica on carbon tetrachloride-induced hepatotoxicity in rats. AB - Among Yoruba herbalists (Southwest Nigeria), hot water infusion of Mangifera indica L. ( Mang Guo) stem bark is reputedly used for the treatment of fever, jaundice and liver disorders. The present study, therefore, investigates the protective effects and mechanism(s) of chemopreventive and curative effects of 125-500 mg/kg/day of Mangifera indica aqueous stem bark extract (MIASE) in acute CCl4-induced liver damage in rats. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day of MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 20% CCl4, i.p.). The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL c), total bilirubin (TB), conjugated bilirubin (CB) and fasting blood glucose (FBG) levels were estimated. In addition, hepatic tissue reduced glutathione (GSH) and the malondialdehyde (MDA) concentrations, catalase (CAT), superoxide (SOD) activities in the hepatic homogenate, and histopathological changes in the rat liver sections were determined. Preliminary qualitative phytochemical screening for bioactive compounds in MIASE was also conducted. Results showed that oral treatment with 125-500 mg/kg/day of MIASE significantly attenuated the increase in serum ALT, AST, ALP, FBG, TB, CB and LDL-c levels in acute liver injury induced by CCl4 treatment. Findings also revealed significant elevations in the serum TC, TG, HDL-c, TP and ALB levels. There was marked architectural remodeling in the hepatic lesions of hepatocyte vacuolation and centrilobular necrosis induced by CCl4 treatment, coupled with significant weight loss. MIASE also markedly enhanced SOD and CAT activities while reducing MAD formation; and increased GSH concentration in the hepatic homogenate compared with untreated CCl4-intoxicated group, with more protection offered in the curative than the chemopreventive models of CCl4 hepatotoxicity. Thus, these results indicate that MIASE has a profound protective effect against acute CCl4-induced hepatotoxicity in rats, which may be due to its free radicals scavenging effect, inhibition of lipid peroxidation, and its ability to increase antioxidant activity. PMID- 26151021 TI - Mainstreaming of Ayurveda, Yoga, Naturopathy, Unani, Siddha, and Homeopathy with the health care delivery system in India. AB - India has a population of 1.21 billion people and there is a high degree of socio cultural, linguistic, and demographic heterogeneity. There is a limited number of health care professionals, especially doctors, per head of population. The National Rural Health Mission has decided to mainstream the Ayurveda, Yoga, Naturopathy, Unani, Siddha, and Homeopathy (AYUSH) system of indigenous medicine to help meet the challenge of this shortage of health care professionals and to strengthen the delivery system of the health care service. Multiple interventions have been implemented to ensure a systematic merger; however, the anticipated results have not been achieved as a result of multiple challenges and barriers. To ensure the accessibility and availability of health care services to all, policy-makers need to implement strategies to facilitate the mainstreaming of the AYUSH system and to support this system with stringent monitoring mechanisms. PMID- 26151022 TI - Creosote bush lignans for human disease treatment and prevention: Perspectives on combination therapy. AB - The medicinal properties of the most successful plant in the deserts of the western hemisphere, the creosote bush (Larrea tridentata), are evidenced by the long traditional usage of the plants by the Native Americans Indian tribes in Southwestern North America and the Amerindians from South America. The plant is rich in simple bisphenyl lignans and tricyclic lignans known as cyclolignans. These compounds are responsible for many of the pharmacological activities of extracts of the plants. Some of these activities, namely antiherpes, antioxidant, antifungal, and anti-inflammatory, were known a century ago. Only recently have further studies revealed other crucial activities of the same plant molecules as powerful agents against human immunodeficiency virus, human papillomavirus, cancer, neurodegenerative diseases, and symptoms of aging. Molecular mechanisms underlying the antiviral and anticancer activities have been elucidated and involve the inhibition of SP1 dependent gene transcription. This review summarizes the recent findings on creosote bush lignans. We introduce the concept of a cocktail of safe well-characterized natural products from the creosote bush that would represent a bridge between oriental herbal medicines and Western drug based therapies. PMID- 26151024 TI - Some Chinese folk prescriptions for wind-cold type common cold. AB - Although self-limiting, the common cold (gan mao) is highly prevalent. There are no effective antivirals to cure the common cold and few effective measures to prevent it, However, for thousands years, Chinese people have treated the common cold with natural herbs, According to the traditional Chinese medicine (TCM) theory ( zhong yi li lun), the common cold is considered as an exterior syndrome, which can be further divided into the wind-cold type ( feng han xing), the wind heat type ( feng re xing), and the summer heat dampness type ( shu re xing). Since the most common type of common cold caught in winter and spring is the wind cold type, the article introduced some Chinese folk prescriptions for the wind cold type common cold with normal and weak physique, respectively. For thousands of years, Chinese folk prescriptions for the common cold, as complementary and alternative medicine (CAM; bu chong yu ti dai yi xue), have been proven to be effective, convenient, cheap, and most importantly, safe. The Chinese folk prescriptions ( zhong guo min jian chu fang) for the wind-cold type common cold are quite suitable for general practitioners or patients with the wind-cold type common cold, to treat the disease. Of course, their pharmacological features and mechanisms of action need to be further studied. PMID- 26151023 TI - Cupping therapy: A prudent remedy for a plethora of medical ailments. AB - Since ancient times, complementary and alternative medicine (CAM; bu chong yu ti dai yi xue) have played an important role in human health and welfare. Many therapeutic approaches in healthcare outside the realm of conventional medicine persist in various parts of the world. There is considerable scientific and commercial potential in CAM, which needs to be explored precisely. Cupping therapy ( ba guan liao fa), one of the CAM, is practiced across the world. This therapy is believed to act by correcting imbalances in the internal bio field, such as by restoring the flow of "Qi (qi)". Cupping involves applying a heated cup to generate a partial vacuum that mobilizes the blood flow and promotes effective healing. This review outlines various tools and techniques of cupping therapy. PMID- 26151025 TI - Re-discovering ancient wheat varieties as functional foods. AB - With the gluten-free food market worth almost $1.6 bn in 2011, there is every reason for renewed interest in ancient grains. This resurgent interest is expressed in re-discovering ancient varieties as functional foods. In particular, people affected by celiac disease have to avoid all gluten in their diet and several ancient grains may offer an important alternative. PMID- 26151026 TI - Annona reticulata Linn. (Bullock's heart): Plant profile, phytochemistry and pharmacological properties. AB - From the beginning of human civilization plants and plant based chemicals are the most important sources of medicines. Phytochemical and different products obtained from plant are used as medicines, pharmaceuticals, cosmetics and food supplements. Annona reticulata Linn. ( niu xin guo; Bullock's heart) is a versatile tree and its fruits are edible. Parts of A. reticulata are used as source of medicine and also for industrial products. It possesses several medicinal properties such as anthelmintic, analgesic, anti-inflammatory, antipyretic, wound healing and cytotoxic effects. It is widely distributed with phytochemicals like tannins, alkaloids, phenols, glycosides, flavonoids and steroids. Present article is an attempt to highlight over taxonomy, morphology, geographical distribution, phytoconstituents and pharmacological activities of A. reticulata reported so far. PMID- 26151027 TI - Efficacy of an Iranian herbal preparation (Lax-Asab) in treating functional constipation: A randomized, placebo-controlled clinical trial. AB - Functional constipation is a common clinical complaint of patients with unsatisfactory treatment outcome. We designed this study to evaluate the efficiency of a traditional herbal preparation (Lax-Asab) in treating chronic constipation. In this double-blind, randomized, placebo-controlled clinical trial, participants with chronic constipation (n = 48) were randomly selected to receive either the Lax-Asab powder (n = 24) or placebo (n = 24) on alternative days for 4 weeks. The Lax-Asab powder contains equal amounts of Cassia angustifolia Vahl. ( xia ye fan xie ye), Mentha piperita L. ( hu jiao bo he), Zingiber officinale Rosc. ( sheng jiang), Glycyrrhiza glabra L. ( gan cao). A total of 40 patients completed the study. We determined the severity of constipation based on defecation frequency (per week) and defecation difficulties. Of the total of 48 patients who participated, 40 completed the trial [24 men (60%), mean age, 21.0 +/- 4.2 years; 16 women (40%), mean age, 20.1 +/- 4.3 years]. The mean of weekly defecation frequency increased in both groups; from 1.8 +/- 0.41 to 4.8 +/- 1.12 times in patients who received Lax-Asab and from 1.7 +/- 0.44 to 2.2 +/- 0.61 times in patients who received placebo. A time treatment interaction showed that this increase was significantly higher in the intervention group. Defecation difficulties improved significantly more in patients who received Lax-Asab than patients who received placebo. There was no statistically significant difference between the two groups with regard to the side effects observed. This study confirms the efficacy and tolerability of an Iranian herbal preparation, Lax-Asab, in treating patients with chronic functional constipation. PMID- 26151028 TI - Pattern of complementary and alternative medicine use among Malaysian stroke survivors: A hospital-based prospective study. AB - Complementary and alternative medicine (CAM; bu chong yu ti dai yi xue) is widely practiced among stroke patients globally. We conducted a study to determine the pattern of CAM use and its associated factors in stroke survivors attending a tertiary hospital in Malaysia within 6 months after the stroke. This was a prospective cohort study that included all stroke patients who were admitted to a tertiary center in Malaysia from December 2009 to December 2010. Patients were interviewed and examined within 72 hours of admission. The sociodemographic data and medical history were collected. Clinical examinations were done to assess the stroke severity using the Scandinavian Stroke Scale and functional status based on modified Barthel index (MBI). Patients were reassessed at 6 months after the stroke on the CAM use and functional status (MBI). The response rate was 92%. The study population consisted of 52 men and 41 women with a mean age of 63.7 +/- 10.3 years. Sixty-seven percent practiced CAM. Massage was the most frequently used method (63.4%), followed by vitamins (7.5%). In multiple logistic regression analysis, functional status (MBI score) on discharge (p = 0.004, odds ratio 1.034, 95% confidence interval 1.01-1.06) and Scandinavian Stroke Scale score (p = 0.045, odds ratio 1.87, 95% confidence interval 1.01-3.43) were significant predictors for use of CAM. In conclusion, the use of CAM among stroke survivors is high. Patients who have better functional status on discharge and less severe stroke are more likely to use CAM. PMID- 26151029 TI - Effects of the extract from roasted chicory (Cichorium intybus L.) root containing inulin-type fructans on blood glucose, lipid metabolism, and fecal properties. AB - The extract from roasted chicory (Cichorium intybus L.; ju ju) root (chicory root extract), which contains inulin-type fructans, has favorable effects including antihyperglycemic and antidyslipidemic effects and the improvement of bowel movement. In this study, we examined the effects of chicory root extract on blood glucose, lipid metabolism, and fecal properties in 47 healthy adult participants in a randomized, double-blind, placebo-controlled study. The participants were divided into a test group that drank chicory root extract and a placebo group that drank nonchicory root extract (ingesting 300 mL daily for 4 weeks). We performed hematological examinations and body composition measurements, and administered a visual analog scale (VAS) questionnaire for fecal properties at the baseline (Week 0) and after the intervention (Week 4) for the two groups. Although no significant differences in fasting plasma glucose or insulin were observed, hemoglobin A1c was found to decrease by ingesting chicory root extract. No intergroup differences in the levels of lipid metabolism parameters were observed. However, the level of adiponectin was significantly improved in the chicory root extract group when the baseline and postintervention values were compared. In addition, chicory root extract tends to improve the VAS score for fecal properties. These results suggest that chicory root extract could delay or prevent the early onset of diabetes mellitus and improve bowel movements. PMID- 26151030 TI - In vivo antimalarial activity of the crude root and fruit extracts of Croton macrostachyus (Euphorbiaceae) against Plasmodium berghei in mice. AB - Euphorbiaceae (Croton macrostachyus H.; ba dou) is used in Ethiopian folklore medicine for the treatment of malaria, gonorrhea, diabetes, wounds, fungal infections, and helminths. No scientific investigations have been performed to substantiate these claims. This study aimed to investigate the in vivo antiplasmodial activity of 80% methanol extract of the fruit and the root of Croton macrostachyus H. in a rodent model of malaria. The rodent malaria parasite Plasmodium berghei was used to inoculate healthy 8-week-old male Swiss albino mice weighing 23-27 g. Each of the hydroalcoholic crude extracts (200 mg/kg, 400 mg/kg, and 600 mg/kg) were administered to different groups of mice. The parameters of parasitemia, survival time, body weight, temperature, and packed cell volume were determined using Peter's test and Rane's test. Both extracts significantly inhibited parasitemia and increased survival time in infected mice. Maximum suppression and prolongation were obtained at the highest doses used in the study. The crude extracts prevented loss of weight and temperature, but did not affect the packed cell volume. This study suggests that the root and fruit extracts of the plant both have promising antiplasmodial activity against Plasmodium berghei in a dose-dependent manner, which supports the folkloric use of the plant for treating malaria. PMID- 26151031 TI - Free radical scavenging ability of Aspalathus linearis in two in vitro models of diabetes and cancer. AB - The free radical scavenging activity of Aspalathus linearis (Rooibos tea) and its effect on reactive oxygen species (ROS), catalase (CAT), and superoxide dismutase (SOD) were investigated in two in vitro disease models of cancer and diabetes. Although the antioxidant activity of this tea has been reported in several studies, its effects in disease models of ROS-induced oxidative stress have not been systematically evaluated to date. The oxygen radical absorbance capacity (ORAC) assay was used in this study to quantify the antioxidant capacity of the extract, whereas the ROS scavenging ability in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs) and HeLa cells were investigated. The CAT and SOD assays were also carried out in the two disease models in order to evaluate the effect of the extract in the stimulation of these two enzyme activities. The extract was observed to have reduced ROS in a dose-dependent manner in both HUVECs and HeLa cells. The stimulation of the CAT and SOD enzyme activities were observed to be dose-dependent as well. The high ORAC value of the extract indicated the presence of antioxidant compounds which could directly quench ROS, whereby this mechanism of action could be hypothesized to have been further complemented through the stimulation of CAT and SOD. Overall, the Aspalathus linearis extract was observed to have increased the CAT and SOD activities in two in vitro disease models of cancer and hyperglycemia. Given the correlation between the ORAC values, the increases in CAT and SOD activities and the reduction in ROS in a dose-dependent manner, it could be hypothesized that the extract had a significant therapeutic potential for either the prevention of the onset of the two diseases or their progression because ROS has been identified as their root causes. PMID- 26151033 TI - Anatomical anterior cruciate ligament reconstruction: transtibial versus outside in technique: SIGASCOT Best Paper Award Finalist 2014. AB - PURPOSE: the aim of this study was to compare clinical results and location of the femoral tunnel with transtibial (TT) and outside-in (OI) techniques in anterior cruciate ligament (ACL) reconstruction using in vivo 3D CT analysis. METHODS: we prospectively followed up 40 ACL reconstructions in which femoral tunnel placement was performed using two different techniques: TT [20] and OI [20]. Clinical evaluation was based on IKDC and KOOS scores and radiographic analysis with specific 3D CT scans. Tunnel coordinates were calculated using the Bernard-Hertel quadrant method to define the insertion point of the ACL. RESULTS: excellent clinical results were achieved in both groups, which showed comparable IKDC and KOOS scores. Two failures were recorded, both in the TT group. In the high-to-low direction, the position of the femoral tunnel, as measured using the quadrant method, was too high in the TT group, compared to what was observed in the OI group: 10.5 +/- 6.9% (0-29%) and 30.2 +/- 5.4% (19-42%), (p=0.043). CONCLUSIONS: we found that with the TT technique, compared with the OI technique, the femoral tunnel was located higher in the high-to-low direction and was in a slightly shallower position in the deep-to-shallow direction. Using the OI technique the femoral tunnel was in a position closer to the anatomical ACL footprint than with the TT technique. A femoral tunnel position far from the anatomical footprint of the native ACL would result in a higher failure rate. LEVEL OF EVIDENCE: level II, prospective comparative study. PMID- 26151032 TI - Studies on synthetic LuxR solo hybrids. AB - A sub-group of LuxR family of proteins that plays important roles in quorum sensing, a process of cell-cell communication, is widespread in proteobacteria. These proteins have a typical modular structure consisting of N-ter autoinducer binding and C-ter helix-turn-helix (HTH) DNA binding domains. The autoinducer binding domain recognizes signaling molecules which are most often N-acyl homoserine lactones (AHLs) but could also be other novel and yet unidentified molecules. In this study we carried out a series of specific domain swapping and promoter activation experiments as a first step to engineer synthetic signaling modules, taking advantage of the modularity and the versatile/diverse signal specificities of LuxR proteins. In our experiments the N-ter domains from different LuxR homologs were either interchanged or placed in tandem followed by a C-ter domain. The rational design of the hybrid proteins was supported by a structure-based homology modeling studies of three members of the LuxR family (i.e., LasR, RhlR, and OryR being chosen for their unique ligand binding specificities) and of selected chimeras. Our results reveal that these LuxR homologs were able to activate promoter elements that were not their usual targets; we also show that hybrid LuxR proteins retained the ability to recognize the signal specific for their N- ter autoinducer binding domain. However, the activity of hybrid LuxR proteins containing two AHL binding domains in tandem appears to depend on the organization and nature of the introduced domains. This study represents advances in the understanding of the modularity of LuxR proteins and provides additional possibilities to use hybrid proteins in both basic and applied synthetic biology based research. PMID- 26151034 TI - The role of the popliteus tendon in total knee arthroplasty: a cadaveric study: SIGASCOT Best Paper Award Finalist 2014. AB - PURPOSE: this study was conducted to investigate the influence of the popliteus tendon (PT) on the static stability of total knee arthroplasty (TKA). METHODS: twenty knees were used. In 10 right knees, a cruciate-retaining (CR) TKA trial prosthesis was implanted; in the other ten knees (left knees), the posterior cruciate ligament was cut and a posterior substitution (PS) TKA trial prosthesis was implanted. Lamina spreaders were set at 100 N of tension, one on the medial and one on the lateral articular space. Gaps were then measured with a caliper before and after PT sectioning. RESULTS: the correlation between femoral dimensions and popliteus insertion distance from articular surfaces was measured with the Pearson correlation index and considered significant. In the CR-TKA group, medial and lateral gap measurements showed a significant increase after PT sectioning both in flexion and in extension. In the PS-TKA group, lateral gap measurements showed a significant increase after PT sectioning both in flexion and in extension, while the medial gap measurements increased significantly only in flexion. CONCLUSIONS: PT sectioning destabilized both the lateral and the medial aspects of the knee. A greater effect was observed in the lateral compartment. The most statistically reliable effect was observed with the knee in flexion. In addition, we observed that preserving the PCL does not prevent lateral gap opening after PT sectioning. CLINICAL RELEVANCE: PT should always be preserved when performing a TKA, because its resection can affect gap balancing, in flexion and in extension. TYPE OF STUDY: controlled laboratory study. PMID- 26151035 TI - Reliability of forced internal rotation and active internal rotation to assess lateral instability of the biceps pulley. AB - PURPOSE: the aim of this study was to investigate the relationship between positive painful forced internal rotation (FIR) and lateral pulley instability in the presence of a pre-diagnosed posterosuperior cuff tear. The same investigation was conducted for painful active internal rotation (AIR). METHODS: a multicenter prospective study was conducted in a series of patients scheduled to undergo arthroscopic posterosuperior cuff repair. Pain was assessed using a visual analog scale (VAS) and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) was administered. The VAS score at rest, DASH score, and presence/absence of pain on FIR and AIR were recorded and their relationships with lesions of the lateral pulley, cuff tear patterns and shape of lesions were analyzed. RESULTS: the study population consisted of 115 patients (mean age: 55.1 years) recruited from 12 centers. The dominant arm was affected in 72 cases (62.6%). The average anteroposterior extension of the lesion was 1.61 cm. The mean preoperative VAS and DASH scores were 6.1 and 41.8, respectively. FIR and AIR were positive in 94 (81.7%) and 85 (73.9%) cases, respectively. The lateral pulley was compromised in 50 cases (43.4%). Cuff tears were partial articular in 35 patients (30.4%), complete in 61 (53%), and partial bursal in 19 (16.5%). No statistical correlation between positive FIR or AIR and lateral pulley lesions was detected. Positive FIR and AIR were statistically associated with complete lesions. Negative FIR was associated with the presence of partial articular tears. CONCLUSIONS: painful FIR in the presence of a postero-superior cuff tear does not indicate lateral pulley instability. When a cuff tear is suspected, positive FIR and AIR are suggestive of full-thickness tear patterns while a negative FIR suggests a partial articular lesion. LEVEL OF EVIDENCE: level I, validating cohort study with good reference standards. PMID- 26151036 TI - Return to sport after ACL reconstruction: how, when and why? A narrative review of current evidence. AB - Allowing a patient to return to sport and unrestricted physical activity after ACL injury and reconstruction is one of the most challenging and difficult decisions an orthopaedic surgeon has to make. Indeed, many factors have to be taken into account before it can be considered safe for a patients to load a reconstructed knee. The current literature contains plenty of studies aimed at evaluating return to sport, and the factors that may affect or predict this outcome, e.g. intrinsic factors like genetics, biology, type of lesion, anatomical features, motivation and psychology, and extrinsic factors such as graft type, surgical technique, rehabilitation protocols, and biological support. It is possible that awareness of these issues could help the clinician to optimise outcomes, and possibly avoid failures too, although as yet no universal criteria for resuming sport have been produced. PMID- 26151037 TI - Revision reverse shoulder arthroplasty in failed shoulder arthroplasties for rotator cuff deficiency. AB - PURPOSE: the aim of this systematic literature review is to report clinical outcomes of reverse shoulder arthroplasty (RSA) used as a revision surgery following failure of the primary implant due to rotator cuff insufficiency. METHODS: a systematic review was performed using the following key words: revision, shoulder, rotator cuff deficiency, outcome assessment, treatment outcome, complications. Studies eligible for inclusion in the review were clinical trials investigating patients in whom a primary shoulder arthroplasty implant with an incompetent rotator cuff was replaced with a reverse shoulder prosthesis. RESULTS: nine articles were identified and further reviewed. The results refer to a total of 226 shoulders that were treated with RSA as revision surgery. The patients in the studies had a mean age ranging from 64 to 72 years and the longest follow-up was 3.8 years. Improvements in function and reduction of pain were shown by many studies, but the mean Constant score ranged from 44.2 to 56. High complication rates (of up to 62%) were recorded, and a mean reoperation rate of 27.5%. CONCLUSIONS: RSA as revision surgery for patients with rotator cuff deficiency is a valid option, and often the only solution available, but it should be limited to elderly patients with poor function and severe pain. LEVEL OF EVIDENCE: level IV, systematic review of level I-IV studies. PMID- 26151038 TI - Stemless shoulder arthroplasty: a literature review. AB - The design of humeral implants for shoulder arthroplasty has evolved over the years. The new-generation modular shoulder prostheses have an anatomical humeral stem that replicates the three-dimensional parameters of the proximal humerus. An anatomical reconstruction is the best way to restore stability and mobility of the prosthetic shoulder and improve implant durability. However, a perfect anatomical match is not always possible in, for example, patients with post traumatic osteoarthritis of the shoulder and deformities in the metaphyseal region. To avoid stem-related complications while retaining the advantages of the fourth generation of shoulder implants, different stemless implants have been developed. The stemless shoulder prosthesis is a new concept in shoulder arthroplasty. The authors review the indications, surgical technique, clinical and radiological midterm results, and complications of these humeral implants. PMID- 26151039 TI - Bi-unicompartmental and combined uni plus patellofemoral replacement: indications and surgical technique. AB - The anatomy and orientation of the condyles and the trochlea are not standard, but related to morphotype, gender and race. Consequently, the extreme variability in their dimension, and in the distance and angle between the axis of the condyles and of the trochlea, often necessitates a "custom-made" replacement. This may be achieved through the use of small implants. Bicompartmental osteoarthritis with intact ligaments should be addressed with bi-unicompartmental (bi-UKR) or UKR plus patellofemoral replacement (PFR). These options allow selective replacement of the worn compartments and a customised fit of the small implants to the native knee anatomy. Clinical consequences are restoration of the native knee kinematics and overall better function. PMID- 26151040 TI - Dual Inhibitors Against Topoisomerases and Histone Deacetylases. AB - Topoisomerases and histone deacetylases (HDACs) are considered as important therapeutic targets for a wide range of cancers, due to their association with the initiation, proliferation and survival of cancer cells. Topoisomerases are involved in the cleavage and religation processes of DNA, while HDACs regulate a dynamic epigenetic modification of the lysine amino acid on various proteins. Extensive studies have been undertaken to discover small molecule inhibitor of each protein and thereby, several drugs have been transpired from this effort and successfully approved for clinical use. However, the inherent heterogeneity and multiple genetic abnormalities of cancers challenge the clinical application of these single targeted drugs. In order to overcome the limitations of a single target approach, a novel approach, simultaneously targeting topoisomerases and HDACs with a single molecule has been recently employed and attracted much attention of medicinal chemists in drug discovery. This review highlights the current studies on the discovery of dual inhibitors against topoisomerases and HDACs, provides their pharmacological aspects and advantages, and discusses the challenges and promise of the dual inhibitors. PMID- 26151042 TI - Association of Dietary Vitamin D and Calcium With Genetic Polymorphisms in Colorectal Neoplasia. AB - The incidence trends of colorectal cancer have varied over time, and there is wide geographical variation across the world. Regarding colorectal cancer, diverse modifiable environmental or intrinsic risk factors have been investigated. This review summarizes the effects of both dietary intake of vitamin D and calcium in particular and diet-associated genetic factors on colorectal cancer risk. We searched the electronic database PubMed for articles published between January 2000 and March 2015. We reviewed case-control studies that included dietary factors, genetic polymorphisms, and gene-diet interactions in association with colorectal cancer risk. Overall, 21 studies were selected as eligible studies. These studies demonstrated that dietary consumption of vitamin D and calcium may decrease the risk of colorectal cancer or adenoma. Colorectal carcinogenesis was discussed in conjunction with dietary factors and mediating genetic factors. The epidemiological findings suggested that the gene-diet interactions may possibly alter the associations between dietary intake, genetic polymorphisms, and the risk of colorectal cancer. However, the reported effects of the same potential factors on colorectal cancer risk were inconsistent, depending on the study population and geographical location. This finding may imply the necessity of considering the environmental differences and genetic variations existing between individuals or specified populations. Therefore, further studies are required to investigate modifiable risk factors in diverse locations to derive useful implications for colorectal neoplasia. PMID- 26151041 TI - Anticancer Effect of Lycopene in Gastric Carcinogenesis. AB - Gastric cancer ranks as the most common cancer and the second leading cause of cancer-related death in the world. Risk factors of gastric carcinogenesis include oxidative stress, DNA damage, Helicobacter pylori infection, bad eating habits, and smoking. Since oxidative stress is related to DNA damage, smoking, and H. pylori infection, scavenging of reactive oxygen species may be beneficial for prevention of gastric carcinogenesis. Lycopene, one of the naturally occurring carotenoids, has unique structural and chemical features that contributes to a potent antioxidant activity. It shows a potential anticancer activity and reduces gastric cancer incidence. This review will summarize anticancer effect and mechanism of lycopene on gastric carcinogenesis based on the recent experimental and clinical studies. PMID- 26151043 TI - Esculetin, a Coumarin Derivative, Exhibits Anti-proliferative and Pro-apoptotic Activity in G361 Human Malignant Melanoma. AB - BACKGROUND: Although esculetin, a coumarin compound, is known to induce apoptosis in human cancer cells, the effects and molecular mechanisms on the apoptosis in human malignant melanoma (HMM) cells are not well understood yet. In this study, we investigated the anti-proliferative effects of esculetin on the G361 HMM cells. METHODS: We analyzed the anti-proliferative effects and molecular mechanisms of esculetin on G361 cells by a 3-(4,5-dimethylthiazol- 2-yl)-5-(3 carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, 4',6-diamidino-2 phenylindole staining and Western blotting. RESULTS: Esculetin exhibited significant anti-proliferative effects on the HMM cells in a dose-dependent manner. Interestingly, we found that esculetin induced nuclear shrinkage and fragmentation, typical apoptosis markers, by suppression of Sp1 transcription factor (Sp1). Notably, esculetin modulated Sp1 downstream target genes including p27, p21 and cyclin D1, resulted in activation of apoptosis signaling molecules such as caspase-3 and PARP in G361 HMM cells. CONCLUSIONS: Our results clearly demonstrated that esculetin induced apoptosis in the HMM cells by downregulating Sp1 protein levels. Thus, we suggest that esculetin may be a potential anti proliferative agent that induces apoptotic cell death in G361 HMM cells. PMID- 26151044 TI - Inhibition of Nuclear Receptor Binding SET Domain 2/Multiple Myeloma SET Domain by LEM-06 Implication for Epigenetic Cancer Therapies. AB - BACKGROUND: Multiple myeloma SET domain (MMSET)/nuclear receptor binding SET domain 2 (NSD2) is a lysine histone methyltransferase (HMTase) and bona fide oncoprotein found aberrantly expressed in several cancers, suggesting potential role for novel therapeutic strategies. In particular, MMSET/NSD2 is emerging as a target for therapeutic interventions against multiple myeloma, especially t(4;14) myeloma that is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma and remains an incurable malignancy. Thus, effective therapeutic strategies are greatly needed. HMTases inhibitors are scarce and no NSDs inhibitors have been isolated. METHODS: We used homology modeling, molecular modeling simulations, virtual ligand screening, computational chemistry software for structure-activity relationship and performed in vitro H3K36 histone lysine methylation inhibitory assay using recombinant human NSD2-SET and human H3.1 histone. RESULTS: Here, we report the discovery of LEM-06, a hit small molecule inhibitor of NSD2, with an IC50 of 0.8 mM against H3K36 methylation in vitro. CONCLUSIONS: We propose LEM-06 as a hit inhibitor that is useful to further optimize for exploring the biology of NSD2. LEM-06 derivatives may pave the way to specific NSD2 inhibitors suitable for therapeutic efforts against malignancies. PMID- 26151045 TI - Constitutive and Inducible Expression of Invasion-related Factors in PC-3 Prostate Cancer Cells. AB - BACKGROUND: Tumor growth and invasion are interconnected with the tumor microenvironment. Overexpression of genes that regulate cancer cell invasion by growth factors, cytokines, and lipid factors can affect cancer aggressiveness. A comparative gene expression analysis between highly invasive and low invasive cells revealed that various genes are differentially expressed in association with invasive potential. In this study, we selected variant PC-3 prostate cancer cell sublines and discovered critical molecules that contributed to their invasive potential. METHODS: The high invasive and low invasive variant PC-3 cell sublines were obtained by serial selection following Matrigel-coated Transwell invasion and were characterized by Transwell invasion, luciferase reporter assay, and Rhotekin pull-down assay. Lysophosphatidic acid (LPA) was added to the cultures to observe the response to this extracellular stimulus. The essential molecules related with cancer invasiveness were detected with Northern blotting, quantitative reverse transcription-polymerase chain reaction, and cDNA microarray. RESULTS: Highly invasive PC-3 cells showed higher nuclear factor kappa B (NF-kappaB), activator protein 1 (AP-1) and RhoA activities than of low invasive PC-3 cells. LPA promoted cancer invasion through NF-kappaB, AP-1, and RhoA activities. Thrombospondin-1, interleukin-8, kallikrein 6, matrix metalloproteinase-1, and tissue factor were overexpressed in the highly invasive PC-3 variant cells and further upregulated by LPA stimulation. CONCLUSIONS: The results suggest that the target molecules are involved in invasiveness of prostate cancer. These molecules may have clinical value for anti-invasion therapy by serving as biomarkers for the prediction of aggressive cancers and the detection of pharmacological inhibitors. PMID- 26151046 TI - Antiangiogenic Therapy Impedes Infiltration by CD4+ and CD8+ Cells Into an Early Colon Tumor. AB - BACKGROUND: While the majority of angiogenesis studies have focused on the late stages of cancer, the emergence of neovascularization in colon tumorigenesis has been observed an earlier stage than expected. Recent reports implied that early angiogenesis might be a defense mechanism to stimulate the natural clearance of microadenomas during colon tumorigenesis. However, little is known about how early angiogenesis affects the natural clearance of tumors. METHODS: Spontaneous colon tumors were developed in adenomatous polyposis coli conditional knockout mice with Cre recombinase adenovirus administration. Vascular endothelial growth factor (VEGF) antagonist, DC101, was administrated to determine the effect of early angiogenesis and then infiltration of immune cells into tumor and concentration of cytokines were evaluated. RESULTS: The continuous administration of the VEGF receptor 2 antagonist DC101 in the mouse models impeded the infiltration by CD4+ and CD8+ cells into the tumor region. Furthermore, the administration of the VEGF antagonist decreased the amounts of anti-tumoral cytokines such as interleukin (IL)-6 and IL-10. CONCLUSIONS: We revealed that newly formed vessels during tumorigenesis can be channels for particular anti tumoral immune cells. Our results may confer insight for the clinical development of an efficient antiangiogenic therapeutic manual and a timely chemoprevention to suppress tumor growth. PMID- 26151047 TI - The Sasa quelpaertensis Leaf Extract Inhibits the Dextran Sulfate Sodium-induced Mouse Colitis Through Modulation of Antioxidant Enzyme Expression. AB - BACKGROUND: Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease. The objective of this study is to investigate the protective effect of Sasa quelpaertensis leaf extract (SQE) against oxidative stress in mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: Mice were treated with SQE (100 mg/kg or 300 mg/kg body weight) by gavage in advance two weeks before inflammation was induced. Then, the mice were administered with 2.5% DSS in drinking water for 7 days and normal drinking water for 7 days between two DSS treatment. Disease activity index values, gut motility, and severity of the resulting oxidative DNA damage were analyzed. The antioxidant effect of SQE was evaluated by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) activity in plasma samples. Catalase activity and expressions levels of glutathione peroxidase 1 (Gpx1), SOD1, and SOD2 were also detected in colon tissues. RESULTS: Administration of SQE significantly reduced the severity of DSS-induced colitis compared to the control (Ctrl) group. Levels of 8-oxo-dG, an oxidative DNA damage marker, were significantly lower in the SQE group compared to the untreated DSS Ctrl group. In the SQE (300 mg/kg) group, MDA levels were significantly lower, while SOD and catalase activity levels in the plasma samples were significantly higher compared with the DSS Ctrl group. The expression levels of the antioxidant enzymes, SOD2 and Gpx1, were significantly higher, while the levels of SOD 1 expression were lower, in the colon tissues of the DSS Ctrl group compared with those of the Ctrl group. In contrast, administration of SQE significantly down-regulated SOD2 and Gpx1 expressions and up-regulated SOD1 expression. CONCLUSIONS: These results indicate that SQE efficiently suppresses oxidative stress in DSS-induced colitis in mice, and its action is associated with the regulation of antioxidant enzymes. PMID- 26151048 TI - Alcohol Drinking, Cigarette Smoking and Risk of Colorectal Cancer in the Korean Multi-center Cancer Cohort. AB - BACKGROUND: The present study aimed to examine the association between cigarette smoking, alcohol consumption and colorectal cancer risk among Korean adults. METHODS: Data from the Korean Multi-center Cancer Cohort between 1993 and 2005 were analyzed. The study population comprised 18,707 subjects aged older than 20 years old. The subjects were followed until December 31, 2011 (median follow-up of 11.2 years). The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence intervals of cigarette smoking and alcohol consumption for colorectal cancer risk. RESULTS: In men, longer duration and higher average amount of alcohol consumption were associated with elevated risk of colorectal cancer (HR 1.93 [1.17-3.18] for >= 30 years of consumption compared to non-drinkers; HR 2.24 [1.31-3.84] for >= 30 g/d). Former smokers showed a non significantly elevated risk of colorectal cancer in men. There was no apparent association between alcohol consumption or cigarette smoking and colorectal cancer risk among women. CONCLUSIONS: Alcohol consumption was associated with increased colorectal cancer risk among Korean men, and both a longer duration and a higher amount of consumption were associated with elevated risk. PMID- 26151049 TI - Total and Dietary Calcium Intake and Colorectal Adenoma in Korean Adults. AB - BACKGROUND: Colorectal cancer in Korea has become more prevalent over the few last decades, and calcium is considered a preventive factor for colorectal cancer development. We examined the associations between total and dietary calcium intake and the prevalence of colorectal adenoma in Korean adults. METHODS: This cross-sectional study included 112 colorectal adenoma cases and 252 adenoma-free non-cases, aged 45 to 71 years, who underwent colonoscopies at the Daegu Catholic University Medical Center from August 2011 to September 2012. Participants were asked about their diet using a validated food frequency questionnaire and about supplement use through interviews. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between total and dietary calcium intake and the prevalence of colorectal adenomas using multivariable logistic regression models. RESULTS: Increasing total calcium intake from foods and supplements was significantly associated with a decreased prevalence of colorectal adenoma in women; comparing the highest quartile with the lowest quartile, the OR (95% CI) was 0.35 (0.15-0.85; P for trend = 0.03). Likewise, high dietary calcium intake from foods was associated with a lower prevalence of colorectal adenoma in women; compared with the lowest quartile, the ORs (95% CIs) were 0.32 (0.13-0.82) for the 3rd quartile and 0.44 (0.19-1.03; P for trend = 0.13) for the 4th quartile. However, the association was not clear for either total or dietary calcium intake among men. CONCLUSIONS: A higher intake of calcium was associated with a reduction of colorectal adenoma prevalence in Korean women. PMID- 26151050 TI - Immunochromatographic Assessment of Salivary Cotinine and Its Correlation With Nicotine Dependence in Tobacco Chewers. AB - BACKGROUND: This study assessed the correlation between nicotine dependence and salivary cotinine levels in tobacco chewers and checked the reliability of Fagerstorm test in tobacco cessation programmes. METHODS: The study sample included 75 tobacco chewers aged between 20 to 50 years. Self-reported nicotine dependence was evaluated using Fagerstorm Test for Nicotine dependence-smokeless tobacco questionnaire. Patients were categorized into low, moderate and high dependent chewers based on their answers to the questionnaire. The unstimulated salivary cotinine levels were measured by immunochromatographic assay using the NicAlert saliva test. Data was analysed using the chi-square test for testing intra-group variation, analysis of variance for testing between-groups variation, and the Spearman coefficient for assessing the association between variables. RESULTS: No statistically significant association was seen between salivary cotinine levels and nicotine dependence. A weak positive correlation was noted between the above variables (r = 0.230). In the group studied, it was evident that the patients were under-reporting the nicotine dependence. CONCLUSIONS: The measurement of salivary cotinine by immunochromatographic assay using NicAlert saliva test is a useful and convenient method for studying the nicotine dependence in tobacco chewers. Immunochromatography-based cotinine test strips are an easy method of detecting salivary cotinine in a dental setup. From this study we are of the opinion that a simple questionnaire like Fagerstorm test can give a less adequate analysis of patient's dependence especially in countries like India, where patients tend to under-report their dependency. Immediate feedback from a chairside test can help both the dentists and patients during a tobacco cessation programme. PMID- 26151051 TI - Retraction: Ethanol Mediates Cell Cycle Arrest and Apoptosis in SK-N-SH Neuroblastoma Cells. PMID- 26151053 TI - 2D DIGE Does Not Reveal all: A Scotopic Report Suggests Differential Expression of a Single "Calponin Family Member" Protein for Tetany of Sphincters! AB - Using 2D differential gel electrophoresis (DIGE) and mass spectrometry (MS), a recent report by Rattan and Ali (2015) compared proteome expression between tonically contracted sphincteric smooth muscles of the internal anal sphincter (IAS), in comparison to the adjacent rectum [rectal smooth muscles (RSM)] that contracts in a phasic fashion. The study showed the differential expression of a single 23 kDa protein SM22, which was 1.87 fold, overexpressed in RSM in comparison to IAS. Earlier studies have shown differences in expression of different proteins like Rho-associated protein kinase II, myosin light chain kinase, myosin phosphatase, and protein kinase C between IAS and RSM. The currently employed methods, despite its high-throughput potential, failed to identify these well-characterized differences between phasic and tonic muscles. This calls into question the fidelity and validatory potential of the otherwise powerful technology of 2D DIGE/MS. These discrepancies, when redressed in future studies, will evolve this recent report as an important baseline study of "sphincter proteome." Proteomics techniques are currently underutilized in examining pathophysiology of hypertensive/hypotensive disorders involving gastrointestinal sphincters, including achalasia, gastroesophageal reflux disease (GERD), spastic pylorus, seen during diabetes or chronic chemotherapy, intestinal pseudo-obstruction, and recto-anal incontinence. Global proteome mapping may provide instant snapshot of the complete repertoire of differential proteins, thus expediting to identify the molecular pathology of gastrointestinal motility disorders currently labeled "idiopathic" and facilitating practice of precision medicine. PMID- 26151052 TI - Endocrine disrupters: the new players able to affect the epigenome. AB - Epigenetics represents the way by which the environment is able to program the genome; there are three main levels of epigenetic control on genome: DNA methylation, post-translational histone modification and microRNA expression. The term Epigenetics has been widened by NIH to include "both heritable changes in gene activity and expression but also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable." These changes might be produced mostly by the early life environment and might affect health influencing the susceptibility to develop diseases, from cancer to mental disorder, during the entire life span. The most studied environmental influences acting on epigenome are diet, infections, wasting, child care, smoking and environmental pollutants, in particular endocrine disrupters (EDs). These are environmental xenobiotics able to interfere with the normal development of the male and female reproductive systems of wildlife, of experimental animals and possibly of humans, disrupting the normal reproductive functions. Data from literature indicate that EDs can act at different levels of epigenetic control, in some cases transgenerationally, in particular when the exposure to these compounds occurs during the prenatal and earliest period of life. Some of the best characterized EDs will be considered in this review. Among the EDs, vinclozolin (VZ), and methoxychlor (MXC) promote epigenetic transgenerational effects. Polychlorinated biphenils (PCBs), the most widespread environmental EDs, affect histone post-translational modifications in a dimorphic way, possibly as the result of an alteration of gene expression of the enzymes involved in histone modification, as the demethylase Jarid1b, an enzyme also involved in regulating the interaction of androgens with their receptor. PMID- 26151054 TI - Effect of chronic alcohol consumption on the development and progression of non alcoholic fatty liver disease (NAFLD). AB - A number of epidemiologic studies show a protective effect of light to moderate daily alcohol consumption on the development of non-alcoholic fatty liver disease (NAFLD). Although these small amounts of ethanol may prevent fatty liver, they may also be a risk factor for other diseases such as breast and colon cancer. Those individuals who have underlying hepatic steatosis or non-alcoholic steatohepatitis (NASH) should not use ethanol chronically since the data available at present do not support a beneficial effect of alcohol in this situation. Especially overweight and obese individuals may be more susceptible towards alcohol even at moderate doses. Animal experiments show a negative effect of ethanol on liver histology in either dietary or genetic NASH models. In addition, patients with NASH reveal a significant increased risk for hepatocellular cancer (HCC) even with social alcohol consumption. Thus, subjects with underlying NASH should abstain from alcohol at any amounts. PMID- 26151055 TI - PNPLA3 genetic variation in alcoholic steatosis and liver disease progression. AB - Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3's function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients. PMID- 26151056 TI - Carotenoids and non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is a growing health problem around the world, especially in developed countries. NAFLD includes all cases of fatty liver disease from simple steatosis to cirrhosis, without excessive alcohol intake, use of steatogenic medication or hereditary disorders. Pathogenesis is associated with dietary high fat intake, decreased free fatty acid (FFA) oxidation, increased hepatic lipogenesis and lipolysis from the adipose tissue. These metabolic alterations contribute to the hepatic fat accumulation. Consequently, stimulated oxidative stress and inflammation play a major role in hepatocellular damage. Therefore, antioxidant and anti-inflammatory agents may have a role in the prevention of this disease. Carotenoids are potent antioxidant and anti inflammatory micronutrients, which have been investigated in the prevention and treatment of NAFLD. The main sources of the carotenoids are fruits and vegetables. In this article we review the potential role and possible molecular mechanism of carotenoids in NAFLD. PMID- 26151057 TI - Dietary saturated fatty acids reduce hepatic lipid accumulation but induce fibrotic change in alcohol-fed rats. AB - BACKGROUND: In this study, we evaluated the influence of an ethanol-containing diet with high saturated fatty acids (SFAs) on alcoholic liver disease (ALD) in rats. METHODS: Male Wistar rats weighing about 160 g were divided into four groups: an ethanol (E) group fed an ethanol-containing liquid diet with 36% total calories as fat (corn oil, olive oil and safflower oil); a control (C) group pair fed an isoenergetic diet without ethanol; an ethanol with saturated fat (EHS) group fed an ethanol-containing diet which contained 40% total calories as fat (90% lard); and a control with saturated fat (CHS) group fed an isoenergetic diet without ethanol, which contained 40% total calories as fat. RESULTS: After 8 weeks of treatment, the liver weight and plasma aspartate aminotransferase (AST) activities in E and EHS groups were significantly higher than those of C group. Significantly higher scores of inflammation, necrosis, and fatty changes were found in E group, whereas significantly higher scores of necrosis, bile duct hyperplasia, and fibrosis were found in EHS group. Although significantly lower plasma adiponectin concentrations were observed in both E and EHS groups, compared to C group, plasma adiponectin in EHS group was significantly higher than that in E group. There was no change in hepatic peroxisome proliferator activated receptor (PPAR)-alpha expression between E and C groups, and rats in EHS group showed a significantly elevated level compared to the other groups. A lower hepatic sirtuins (SIRT)-1 level was found in E group, but it did not reach statistical significance. Moreover, the highest plasma TGF-beta1 level was found in EHS group. Compared to C group, the hepatic reduced glutathione/oxidized glutathione ratio and thiobarbituric acid (TBA)-reactive substance level were significantly increased in E and EHS groups; however, there was no significant difference between E and EHS groups. Significantly increased hepatic CYP2E1 expression was observed in both E and EHS groups, while at the same time, hepatic CYP2E1 in EHS group was the highest among all groups. The hepatic tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 concentrations in the E group were significantly higher than those in C group, whereas the hepatic IL-6 and IL-10 concentrations in ES group were significantly lower than those of E group. CONCLUSIONS: These results suggested that dietary saturated fats may inhibit hepatic fat accumulation and induce hepatic fibrosis in rats under chronic alcohol intake. PMID- 26151058 TI - DGAT1-deficiency affects the cellular distribution of hepatic retinoid and attenuates the progression of CCl4-induced liver fibrosis. AB - BACKGROUND: Diacylglycerol O-acyltransferase 1 (DGAT1) catalyzes the final step of triglyceride synthesis, transferring an acyl group from acyl-CoA to diacylglycerol. DGAT1 also catalyzes the acyl-CoA-dependent formation of retinyl esters in vitro and in mouse intestine and skin. Although DGAT1 is expressed in both hepatocytes and hepatic stellate cells (HSCs), we reported genetic and nutritional studies that established that DGAT1 does not contribute to retinyl ester formation in the liver. METHODS: We now have explored in more depth the role(s) of DGAT1 in hepatic retinoid metabolism and storage. RESULTS: Our data show that DGAT1 affects the cellular distribution between hepatocytes and HSCs of stored and newly absorbed dietary retinol. For livers of Dgat1-deficient mice, a greater percentage of stored retinyl ester is present in HSCs at the expense of hepatocytes. This is also true for newly absorbed oral [(3)H]retinol. These differences are associated with significantly increased expression, by 2.8-fold, of cellular retinol-binding protein, type I (RBP1) in freshly isolated HSCs from Dgat1-deficient mice, raising the possibility that RBP1, which contributes to retinol uptake into cells and retinyl ester synthesis, accounts for the differences. We further show that the retinyl ester-containing lipid droplets in HSCs are affected in Dgat1-null mice, being fewer in number but, on average, larger than in wild type (WT) HSCs. Finally, we demonstrate that DGAT1 affects experimentally induced HSC activation in vivo but that this effect is independent of altered retinoic acid availability or effects on gene expression. CONCLUSIONS: Our studies establish that DGAT1 has a role in hepatic retinoid storage and metabolism, but this does not involve direct actions of DGAT1 in retinyl ester synthesis. PMID- 26151059 TI - Detectability and clinical significance of serum hepatitis B virus ribonucleic acid. AB - Serum hepatitis B virus (HBV) RNA is detected during treatment with nucleoside analogue as a consequence of interrupted reverse transcription (RT) and unaffected replicative intermediates. The presence of serum HBV RNA in chronic HBV patients is confirmed by using ribonuclease digestion. Serum HBV RNA is differentially inhibited by interferon, but not by nucleoside analogue. The inhibitory effect of interferon on HBV RNA replicative intermediates may potentiate the suppression of HBV replication. Clinical significance of serum HBV RNA includes: (I) reflect the antiviral potency of nucleoside analogue; (II) predictor of early emergence of viral mutation during lamivudine therapy; (III) independently predict initial virologic response or earlier HBV suppression during nucleoside analogue therapy; (IV) predict HBV reactivation after discontinuation of nucleoside analogue. Thus, serum HBV RNA might be useful to optimize treatment efficacy in patients with chronic HBV, including shifting of oral antivirals or conversion to immunomodulatory agent i.e., interferon. Furthermore, serum HBV RNA levels correlate better with serum quantitative HBsAg (qHBsAg) than with serum HBV DNA levels. The predictive role of serum HBV RNA in long-term treatment effects of nucleoside analogue needs further study. PMID- 26151060 TI - Prediction of postoperative liver failure in patients diagnosed with hepatocellular carcinoma using (99m)Tc-GSA SPECT/CT. PMID- 26151061 TI - Decoding multifocal hepatocellular carcinoma: an opportune pursuit. AB - Hepatocellular carcinoma (HCC) is a malignancy with major worldwide prevalence and a poor overall prognosis. About 75% of all HCC cases are initially diagnosed as multiple tumors, presenting a particular challenge for aggressive surgical therapy. Multiple HCC may result from multicentric occurrence (MO-HCC) or intrahepatic metastases (IM-HCC), corresponding to highly dissimilar clinical outcomes. Reliable distinction of these two mechanisms is therefore paramount in optimizing the management of multiple HCC. In a recent work, Miao et al. adopted a multi-omics approach to find key parameters of different clonality in MO-HCC vs. IM-HCC and link these data to tumor behavior and prognosis in a cohort of patients with HBV-related HCC. The mitotic checkpoint regulator TTK has emerged from this analysis as a novel biomarker that may predict aggressive behavior and early postoperative recurrence of HCC. PMID- 26151062 TI - Use of irreversible electroporation in unresectable pancreatic cancer. AB - Irreversible electroporation is a non-thermal injury ablative modality that has been in clinical use since 2008 in the treatment of locally advanced soft tissue tumors. It has been reported to be utilized intraoperatively, laparoscopically or percutaneously. The method of action of IRE relies on a high voltage (maximum 3,000 volts) small microsecond pulse lengths (70 to 90 microseconds) to induce cell membrane porosity which leads to slow/protracted cell death over time. One of the largest unmet needs in oncology that IRE has been utilized is in locally advanced (stage III) pancreatic cancer. Recent studies have demonstrated the safety and palliation with encouraging improvement in overall survival. Its inherent limitation still remains tissue heterogeneity and the unique settings based on tumor histology and prior induction therapy. There remains a high technical demand of the end-user and the more extensive knowledge transfer which makes the learning curve longer in order to achieve appropriate and safe utilization. PMID- 26151063 TI - Endoscopic extraction of biliary stones and a migrated endoclip for acute pancreatitis. PMID- 26151064 TI - Major hepatectomy for a symptomatic giant liver cavernous hemangioma. PMID- 26151065 TI - Large-scale production of lentiviral vector in a closed system hollow fiber bioreactor. AB - Lentiviral vectors are widely used in the field of gene therapy as an effective method for permanent gene delivery. While current methods of producing small scale vector batches for research purposes depend largely on culture flasks, the emergence and popularity of lentiviral vectors in translational, preclinical and clinical research has demanded their production on a much larger scale, a task that can be difficult to manage with the numbers of producer cell culture flasks required for large volumes of vector. To generate a large scale, partially closed system method for the manufacturing of clinical grade lentiviral vector suitable for the generation of induced pluripotent stem cells (iPSCs), we developed a method employing a hollow fiber bioreactor traditionally used for cell expansion. We have demonstrated the growth, transfection, and vector-producing capability of 293T producer cells in this system. Vector particle RNA titers after subsequent vector concentration yielded values comparable to lentiviral iPSC induction vector batches produced using traditional culture methods in 225 cm(2) flasks (T225s) and in 10-layer cell factories (CF10s), while yielding a volume nearly 145 times larger than the yield from a T225 flask and nearly three times larger than the yield from a CF10. Employing a closed system hollow fiber bioreactor for vector production offers the possibility of manufacturing large quantities of gene therapy vector while minimizing reagent usage, equipment footprint, and open system manipulation. PMID- 26151066 TI - Structure-based redesign of lysostaphin yields potent antistaphylococcal enzymes that evade immune cell surveillance. AB - Staphylococcus aureus infections exert a tremendous burden on the health-care system, and the threat of drug-resistant strains continues to grow. The bacteriolytic enzyme lysostaphin is a potent antistaphylococcal agent with proven efficacy against both drug-sensitive and drug-resistant strains; however, the enzyme's own bacterial origins cause undesirable immunogenicity and pose a barrier to clinical translation. Here, we deimmunized lysostaphin using a computationally guided process that optimizes sets of mutations to delete immunogenic T cell epitopes without disrupting protein function. In vitro analyses showed the methods to be both efficient and effective, producing seven different deimmunized designs exhibiting high function and reduced immunogenic potential. Two deimmunized candidates elicited greatly suppressed proliferative responses in splenocytes from humanized mice, while at the same time the variants maintained wild-type efficacy in a staphylococcal pneumonia model. Overall, the deimmunized enzymes represent promising leads in the battle against S. aureus. PMID- 26151068 TI - In memoriam: Professor Thomas (Tom) Trauer (1944-2013). PMID- 26151069 TI - In memoriam: Hector Lopez (1947-2014). PMID- 26151067 TI - Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization. AB - The polarization of tissue resident macrophages toward the alternatively activated, anti-inflammatory M2 phenotype is believed to positively impact obesity and insulin resistance. Here we show that the soluble form of the extracellular domain (ECD) of C-type lectin-like receptor 2, CLEC2, regulates Kupffer cell polarization in the liver and improves glucose and lipid parameters in diabetic animal models. Over-expression of Fc-CLEC2(ECD) in mice via in vivo gene delivery, or injection of recombinant Fc-CLEC2(ECD) protein, results in a reduction of blood glucose and liver triglyceride levels and improves glucose tolerance. Furthermore, Fc-CLEC2(ECD) treatment improves cytokine profiles and increases both the M2 macrophage population and the genes involved in the oxidation of lipid metabolism in the liver. These data reveal a previously unidentified role for CLEC2 as a regulator of macrophage polarity, and establish CLEC2 as a promising therapeutic target for treatment of diabetes and liver disease. PMID- 26151070 TI - Leisure activities: The power of a pastime. PMID- 26151071 TI - Dysplastic changes of peripheral eosinophils in acute myeloid leukemia with myelodysplastic syndrome-related features. PMID- 26151072 TI - Assessing foetal cardiac anomalies using echocardiography. PMID- 26151073 TI - Pregnancy hormones in cardiovascular disease. PMID- 26151074 TI - Marfan syndrome and pregnancy:monitoring and management. PMID- 26151075 TI - Underestimated risk for life-threatening ventricular arrhythmias in newly diagnosed peripartum cardiomyopathy? PMID- 26151076 TI - Unravelling the reactive oxygen and reactive nitrogen signalling networks in plants. PMID- 26151077 TI - Teleoncology for gynecologic cancers. AB - Teleoncology describes cancer care provided remotely to improve access to care in rural or underserved areas. In the United States, 14.8 million women live more than 50 miles away from the closest gynecologic oncologist; 4.3 million women live more than 100 miles distant. Teleoncology may therefore partially relieve the geographic barriers to high-quality gynecologic cancer care these women experience. Little has been published on the feasibility of remote provision of high-quality care for gynecologic cancers, perhaps owing to the particular difficulties inherent in remote management of patients who may require both medical and surgical intervention. In this article, we review the data supporting the use of telemedicine in the treatment of cancer patients with a specific focus on applicability to management of gynecologic malignancies. We further add our group's experience with the treatment of rural, underserved gynecologic cancer patients. We believe that development of teleoncologic systems is critical to ensure that all women have access to high-quality gynecologic cancer care, regardless of where they reside. PMID- 26151079 TI - Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development. AB - Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed. PMID- 26151080 TI - Reactive Molecular Dynamics Simulations on the Disintegration of PVDF, FP-POSS, and Their Composite during Atomic Oxygen Impact. AB - Poly(vinylidene fluoride) (PVDF) is a kind of important piezoelectric polymer used in spacecraft industry. But the atomic oxygen (AO) is the most abundant element in the low Earth orbit (LEO) environment. AO collision degradation is an important issue in the application of PVDF on spacecrafts. To investigate the erosion behaviors of PVDF during AO impacts and how to improve the stability of PVDF against AO impacts, the temperature evolution, mass loss, and erosion yields of neat PVDF, neat polyhedral oligomeric silsesquioxanes compound (3,3,3 trifluoropropyl)8Si8O12 (FP-POSS) and the PVDF/FP-POSS composite under AO impacts, as well as some key disintegrated structures and separated chemical compositions, were researched using the molecular dynamics (MD) simulations and the reactive ReaxFF force field. The simulation erosion yield result of PVDF is very close to the experiment results, which shows our simulations are reliable. The results of the temperature evolution, mass loss, and erosion yield of three materials show that the antierosion performance of PVDF is not outstanding. However, incorporating FP-POSS into PVDF matrix enhances the stability of PVDF against AO impact greatly and reduces the temperature rise, mass loss, and the erosion yield of PVDF rapidly. A detailed analysis on the flight chemical compositions and key snapshots of the structures reveals that the erosion process on PVDF and PVDF/FP-POSS is continuous and should be derived from the same PVDF matrix in two materials. In contrast, the erosion process on FP-POSS is stepped. The erosion will not take place until the number of AO reaches a specific value. There is a barrier for the erosion of high-energy AO because of the stable cagelike Si-O frame in FP-POSS molecules. This should be chiefly responsible for the high stability of FP-POSS and the reinforcement mechanism of FP-POSS on PVDF against AO impacts. This work is helpful for people to understand the erosion details of PVDF and POSS and provides valuable information to design effective protective structure for PVDF against AO impacts in LEO environment. PMID- 26151081 TI - COPD: Do Imaging Measurements of Emphysema and Airway Disease Explain Symptoms and Exercise Capacity? AB - PURPOSE: To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to moderate disease. MATERIALS AND METHODS: Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA compliant protocol and underwent spirometry and plethysmography, completed the St George's Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT). Emphysema was estimated by using the MR imaging apparent diffusion coefficient (ADC) and the relative area of the CT attenuation histogram with attenuation of -950 HU or less (RA950). Airway disease was measured by using the CT airway wall thickness of airways with an internal perimeter of 10 mm and total airway count. Ventilation defect percentage at (3)He MR imaging was used to measure ventilation. Multivariable regression models for the 6MWD and SGRQ symptom subscore were used to evaluate the relationships between physiologic and imaging measurements. RESULTS: Multivariate modeling for the 6MWD in 80 patients with GOLD grade U-II COPD showed that ADC (beta = 0.34, P = .04), diffusing capacity of the lung for carbon monoxide (beta = 0.60, P = .0008), and residual volume/total lung capacity (beta = -0.26, P = .02) were significant variables, while forced expiratory volume in 1 second (FEV1) and airway disease measurements were not. In 36 patients with GOLD grade III or IV disease, FEV1 (beta = 0.48, P = .01) was the only significant contributor in a multivariate model for 6MWD. MR imaging emphysema measurements also made the greatest relative contribution to symptoms in patients with milder (GOLD grade U-II) COPD (ADC: beta = 0.60, P = .005; RA950: beta = -0.52, P = .02; FEV1: beta = -0.45, P = .0002) and in grade III or IV disease (ADC: beta = 0.95, P = .01; RA950: beta = -0.62, P = .07; airway count: beta = -0.49, P = .01). CONCLUSION: In patients with mild-to-moderate COPD, MR imaging emphysema measurements played a dominant role in the expression of exercise limitation, while both CT and MR imaging measurements of emphysema explained symptoms. PMID- 26151082 TI - Optimization of the Sensitization Process and Stability of Octadentate Eu(III) 1,2-HOPO Complexes. AB - The synthesis of a series of octadentate ligands containing the 1-hydroxypyridin 2-one (1,2-HOPO) group in complex with europium(III) is reported. Within this series, the central bridge connecting two diethylenetriamine units linked to two 1,2-HOPO chromophores at the extremities (5-LIN-1,2-HOPO) is varied from a short ethylene chain (H(2,2)-1,2-HOPO) to a long pentaethylene oxide chain (H(17O5,2) 1,2-HOPO). The thermodynamic stability of the europium complexes has been studied and reveals these complexes may be effective for biological measurements. Extension of the central bridge results in exclusion of the inner-sphere water molecule observed for [Eu(H(2,2)-1,2-HOPO)](-) going from a nonacoordinated to an octacoordinated Eu(III) ion. With the longer chain length ligands, the complexes display increased luminescence properties in aqueous medium with an optimum of 20% luminescence quantum yield for the [Eu(H(17O5,2)-1,2-HOPO)](-) complex. The luminescence properties for [Eu(H(14O4,2)-1,2-HOPO)](-) and [Eu(H(17O5,2)-1,2 HOPO)](-) are better than that of the model bis-tetradentate [Eu(5LIN(Me)-1,2 HOPO)2](-) complex, suggesting a different geometry around the metal center despite the geometric freedom allowed by the longer central chain in the H(mOn,2) scaffold. These differences are also evidenced by examining the luminescence spectra at room temperature and at 77 K and by calculating the luminescence kinetic parameters of the europium complexes. PMID- 26151083 TI - Attenuation of hyperoxia-induced lung injury in neonatal rats by 1alpha,25 Dihydroxyvitamin D3. AB - BACKGROUND: Mounting evidence suggests that Toll-like receptor (TLRs) plays an important role in oxidative stress and is implicated in the pathogenesis of hyperoxic lung injury. 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonally active form of vitamin D, not only plays an essential role in mineral balance, but also possesses immunomodulatory and antioxidant properties. Besides, Vitamin D3 is involved in the regulation of TLRs signaling. The present study was designed to investigate whether 1,25(OH)2D3 attenuates hyperoxia-induced lung injury by regulating TLRs signaling in neonatal rats. METHODS: Pups were divided into four groups: normoxia control group (NC), normoxia plus 1,25(OH)2D3 treatment group (ND), hyperoxia control group (HC), and hyperoxia plus 1,25(OH)2D3 treatment group (HD). Lung tissues were collected for histological examination and detection of mRNA and protein expressions. RESULTS: Treatment of hyperoxia-exposed animals with 1,25(OH)2D3 resulted in significantly increased body weight and reduced hyperoxia-induced lung injury. Moreover, 1,25(OH)2D3 significantly downregulated the expression of TLR4, NF-kappaB, and the inflammatory cytokines TNF-alpha, IL-1beta, and IL-6. CONCLUSIONS: 1,25(OH)2D3 could attenuate hyperoxia-induced lung injury in neonatal rats, possibly by regulating TLR4/NF-kappaB signaling. PMID- 26151084 TI - When Good Intentions Go Awry: Modification of a Recombinant Monoclonal Antibody in Chemically Defined Cell Culture by Xylosone, an Oxidative Product of Ascorbic Acid. AB - With the advent of new initiatives to develop chemically defined media, cell culture scientists screen many additives to improve cell growth and productivity. However, the introduction or increase of supplements, typically considered beneficial or protective on their own, to the basal media or feed stream may cause unexpected detrimental consequences to product quality. For instance, because cultured cells are constantly under oxidative stress, ascorbic acid (vitamin C, a potent natural reducing agent) is a common additive to cell culture media. However, as reported herein, a recombinant monoclonal antibody (adalimumab) in cell culture was covalently modified by xylosone (molecular weight 148), an oxidative product of ascorbate. Containing reactive carbonyl groups, xylosone modifies various amines (e.g., the N-termini of the heavy and light chains and susceptible lysines), forming either hemiaminal (+148 Da) or Schiff base (imine, +130 Da) products. Our findings show, for the first time, that ascorbate-derived xylosone can contribute to an increase in molecular heterogeneity, such as acidic species. Our work serves as a reminder that additives to cell culture and their metabolites may become reactive and negatively impact the overall product quality and should be carefully monitored with any changes in cell culture conditions. PMID- 26151085 TI - Design Principles of DNA Enzyme-Based Walkers: Translocation Kinetics and Photoregulation. AB - Dynamic DNA enzyme-based walkers complete their stepwise movements along the prescribed track through a series of reactions, including hybridization, enzymatic cleavage, and strand displacement; however, their overall translocation kinetics is not well understood. Here, we perform mechanistic studies to elucidate several key parameters that govern the kinetics and processivity of DNA enzyme-based walkers. These parameters include DNA enzyme core type and structure, upper and lower recognition arm lengths, and divalent metal cation species and concentration. A theoretical model is developed within the framework of single-molecule kinetics to describe overall translocation kinetics as well as each reaction step. A better understanding of kinetics and design parameters enables us to demonstrate a walker movement near 5 MUm at an average speed of ~1 nm s(-1). We also show that the translocation kinetics of DNA walkers can be effectively controlled by external light stimuli using photoisomerizable azobenzene moieties. A 2-fold increase in the cleavage reaction is observed when the hairpin stems of enzyme catalytic cores are open under UV irradiation. This study provides general design guidelines to construct highly processive, autonomous DNA walker systems and to regulate their translocation kinetics, which would facilitate the development of functional DNA walkers. PMID- 26151087 TI - Typologies of Childhood Exposure to Violence: Associations With College Student Mental Health. AB - OBJECTIVE: This study examined typologies of childhood violence exposure (CVE) and the associations of profiles with current demographic characteristics and mental health in emerging adulthood. PARTICIPANTS: The study evaluated a sample of college students from 2 US geographic regions (Midwest, n = 195; Southeast, n = 200). METHODS: An online questionnaire (collected 2013-2014) assessed CVE and current mental health. Latent class analysis was used to identify typologies of CVE. Follow-up analyses were conducted to distinguish differences between typologies in demographic characteristics and mental health. RESULTS: Four distinct profiles emerged: High-Exposed, Domestic-Exposed, Community-Exposed, and Low-Exposed. High- and Domestic-Exposed groups were more likely to be first generation college students and to experience symptoms of psychopathology. CONCLUSIONS: This study offers a unique presentation of CVE profiles and a nuanced interpretation of their differential relationship to current demographic characteristics and mental health. It may befit university mental health initiatives to engage first-generation students and utilize comprehensive assessments of previous victimization. PMID- 26151088 TI - Molecular Catalysts for Water Oxidation. PMID- 26151086 TI - Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics. AB - Compensatory islet response is a distinct feature of the prediabetic insulin resistant state in humans and rodents. To identify alterations in the islet proteome that characterize the adaptive response, we analyzed islets from 5 month old male control, high-fat diet fed (HFD), or obese ob/ob mice by LC-MS/MS and quantified ~1100 islet proteins (at least two peptides) with a false discovery rate < 1%. Significant alterations in abundance were observed for ~350 proteins among groups. The majority of alterations were common to both models, and the changes of a subset of ~40 proteins and 12 proteins were verified by targeted quantification using selected reaction monitoring and western blots, respectively. The insulin-resistant islets in both groups exhibited reduced expression of proteins controlling energy metabolism, oxidative phosphorylation, hormone processing, and secretory pathways. Conversely, an increased expression of molecules involved in protein synthesis and folding suggested effects in endoplasmic reticulum stress response, cell survival, and proliferation in both insulin-resistant models. In summary, we report a unique comparison of the islet proteome that is focused on the compensatory response in two insulin-resistant rodent models that are not overtly diabetic. These data provide a valuable resource of candidate proteins to the scientific community to undertake further studies aimed at enhancing beta-cell mass in patients with diabetes. The data are available via the MassIVE repository, under accession no. MSV000079093. PMID- 26151089 TI - Concentration, size, and density of total suspended particulates at the air exhaust of concentrated animal feeding operations. AB - Total suspended particulate (TSP) samples were seasonally collected at the air exhaust of 15 commercial concentrated animal feeding operations (CAFOs; including swine finishing, swine farrowing, swine gestation, laying hen, and tom turkey) in the U.S. Midwest. The measured TSP concentrations ranged from 0.38 +/- 0.04 mg m 3 (swine gestation in summer) to 10.9 +/- 3.9 mg m-3 (tom turkey in winter) and were significantly affected by animal species, housing facility type, feeder type (dry or wet), and season. The average particle size of collected TSP samples in terms of mass median equivalent spherical diameter ranged from 14.8 +/- 0.5 um (swine finishing in winter) to 30.5 +/- 2.0 um (tom turkey in summer) and showed a significant seasonal effect. This finding affirmed that particulate matter (PM) released from CAFOs contains a significant portion of large particles. The measured particle size distribution (PSD) and the density of deposited particles (on average 1.65 +/- 0.13 g cm-3) were used to estimate the mass fractions of PM10 and PM2.5 (PM <= 10 and <= 2.5 MUm, respectively) in the collected TSP. The results showed that the PM10 fractions ranged from 12.7 +/- 5.1% (tom turkey) to 21.1 +/- 3.2% (swine finishing), whereas the PM2.5 fractions ranged from 3.4 +/- 1.9% (tom turkey) to 5.7 +/- 3.2% (swine finishing) and were smaller than 9.0% at all visited CAFOs. This study applied a filter-based method for PSD measurement and deposited particles as a surrogate to estimate the TSP's particle density. The limitations, along with the assumptions adopted during the calculation of PM mass fractions, must be recognized when comparing the findings to other studies. PMID- 26151091 TI - Enhancing the Thermoelectric Figure of Merit by Low-Dimensional Electrical Transport in Phonon-Glass Crystals. AB - Low-dimensional electronic and glassy phononic transport are two important ingredients of highly efficient thermoelectric materials, from which two branches of thermoelectric research have emerged. One focuses on controlling electronic transport in the low dimension, while the other focuses on multiscale phonon engineering in the bulk. Recent work has benefited much from combining these two approaches, e.g., phonon engineering in low-dimensional materials. Here we propose to employ the low-dimensional electronic structure in bulk phonon-glass crystals as an alternative way to increase the thermoelectric efficiency. Through first-principles electronic structure calculations and classical molecular dynamics simulations, we show that the pi-pi-stacking bis(dithienothiophene) molecular crystal is a natural candidate for such an approach. This is determined by the nature of its chemical bonding. Without any optimization of the material parameters, we obtained a maximum room-temperature figure of merit, ZT, of 1.48 at optimal doping, thus validating our idea. PMID- 26151092 TI - Assessment of Genetic Markers for Tracking the Sources of Human Wastewater Associated Escherichia coli in Environmental Waters. AB - In this study, we have evaluated the performance characteristics (host specificity and -sensitivity) of four human wastewater-associated Escherichia coli (E. coli) genetic markers (H8, H12, H14, and H24) in 10 target (human) and nontarget (cat, cattle, deer, dog, emu, goat, horse, kangaroo, and possum) host groups in Southeast Queensland, Australia. The overall host-sensitivity values of the tested markers in human wastewater samples were 1.0 (all human wastewater samples contained the E. coli genetic markers). The overall host-specificity values of these markers to differentiate between human and animal host groups were 0.94, 0.85, 0.72, and 0.57 for H8, H12, H24, and H14, respectively. Based on the higher host-specificity values, H8 and H12 markers were chosen for a validation environmental study. The prevalence of the H8 and H12 markers was determined among human wastewater E. coli isolates collected from a wastewater treatment plant (WWTP). Among the 97 isolates tested, 44 (45%) and 14 (14%) were positive for the H8 and H12 markers, respectively. A total of 307 E. coli isolates were tested from environmental water samples collected in Brisbane, of which 7% and 20% were also positive for the H8 and H12 markers, respectively. Based on our results, we recommend that these markers could be useful when it is important to identify the source(s) of E. coli (whether they originated from human wastewater or not) in environmental waters. PMID- 26151095 TI - Screening of Transforming Growth Factor Beta 3 and Jagged2 Genes in the Malay Population With Nonsyndromic Cleft Lip With or Without Cleft Palate. AB - OBJECTIVE: To determine the prevalence of mutations in transforming growth factor beta 3 (TGFbeta3) and Jagged2 genes and their association with nonsyndromic cleft lip with or without cleft palate (CL+/-P) patients. DESIGN: Cross-sectional study on nonsyndromic CL+/-P and noncleft patients. SETTING: Reconstructive clinic and outpatient dental clinic, Hospital Universiti Sains Malaysia. PATIENTS: Blood samples of 96 nonsyndromic CL+/-P and 96 noncleft subjects. MAIN OUTCOME MEASURE: Prevalence and association of mutations in TGFbeta3 and Jagged2 genes with nonsyndromic CL+/-P. RESULTS: Most of the nonsyndromic CL+/-P patients (53.1%) had left unilateral CLP. There were slightly more females (56.6%) compared with males. The prevalence of the mutations in the TGFbeta3 gene was 17.7% (95% confidence interval [CI]: 9.5, 24.5) and in the Jagged2 gene was 12.5% (95% CI: 5.5, 18.5), which was higher compared with the noncleft group. For the TGFbeta3 gene, there was no mutation in the coding region in either of the groups. All variants were single nucleotide polymorphisms located within the intronic flanking region. Two variants were identified (g.15812T>G and g.15966A>G) in both nonsyndromic CL+/-P and noncleft patients. However, the association was not significant (P > .05). Three variants (g.19779C>T, g.19547G>A, and g.19712C>T) were identified in the Jagged2 gene among nonsyndromic CL+/-P and noncleft patients. Only g.19712C>T showed a significant association with nonsyndromic CL+/ P patients (P = .039). CONCLUSION: g.19712C>T might play a crucial role in the development of cleft lip and palate. To the best of our knowledge, this is the first report of the mutation found within intron 13 of the Jagged2 gene among nonsyndromic CL+/-P Malay patients. PMID- 26151090 TI - A Randomized, Placebo-controlled Trial of Roflumilast. Effect on Proline-Glycine Proline and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Roflumilast is a therapeutic agent in the treatment of chronic obstructive pulmonary disease (COPD). It has antiinflammatory effects; however, it is not known whether it can affect a biologic pathway implicated in COPD pathogenesis and progression. The self-propagating acetyl-proline-glycine-proline (AcPGP) pathway is a novel means of neutrophilic inflammation that is pathologic in the development of COPD. AcPGP is produced by extracellular matrix collagen breakdown with prolyl endopeptidase and leukotriene A4 hydrolase serving as the enzymes responsible for its production and degradation, respectively. OBJECTIVES: We hypothesized that roflumilast would decrease AcPGP, halting the feed-forward cycle of inflammation. METHODS: We conducted a single-center, placebo-controlled, randomized study investigating 12 weeks of roflumilast treatment added to current therapy in moderate-to-severe COPD with chronic bronchitis. Subjects underwent sputum and blood analyses, pulmonary function testing, exercise tolerance, and quality-of-life assessment at 0, 4, and 12 weeks. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients were enrolled in the intention-to-treat analysis. Roflumilast treatment decreased sputum AcPGP by more than 50% (P < 0.01) and prolyl endopeptidase by 46% (P = 0.02), without significant improvement in leukotriene A4 hydrolase activity compared with placebo. Roflumilast also reduces other inflammatory markers. There were no significant changes in lung function, quality of life, or exercise tolerance between roflumilast- and placebo-treated groups. CONCLUSIONS: Roflumilast reduces pulmonary inflammation through decreasing prolyl endopeptidase activity and AcPGP. As expected for lower AcPGP levels, markers of neutrophilic inflammation are blunted. Inhibiting this self propagating pathway lessens the overall inflammatory burden, which may alter the natural history of COPD, including the risk of exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT 01572948). PMID- 26151096 TI - Computerized Clinical Decision Support to Prevent Venous Thromboembolism Among Hospitalized Patients: Proximal Outcomes from a Multiyear Quality Improvement Project. AB - Despite venous thromboembolism (VTE) policy initiatives, gaps exist between guidelines and practice. In response, hospitals implement clinical decision support (CDS) systems to improve VTE prophylaxis. To assess the impact of a VTE CDS on reducing incidence of VTE, this study used a pretest/posttest, longitudinal, cohort design incorporating electronic health record (EHR) data from one urban tertiary and level 1 trauma center, and one suburban hospital. VTE CDS was embedded into the EHR system. The study included 45,046 admissions; 171,753 patient days; and 110 VTE events. The VTE rate declined from 0.954 per 1,000 patient days to 0.434 comparing baseline to full VTE CDS. Compared to baseline, patients benefitting from VTE CDS were 35% less likely to have a VTE. VTE CDS utilization achieved 78.4% patients assessed within 24 hr from admission, 64.0% patients identified at risk, and 47.7% patients at risk for VTE with an initiated VTE interdisciplinary plan of care. CDS systems with embedded algorithms, alerts, and notification capabilities enable physicians at the point of care to utilize guidelines and make impactful decisions to prevent VTE. This study demonstrates a phased-in implementation of VTE CDS as an effective approach toward VTE prevention. Implications for future research and quality improvement are discussed as well. PMID- 26151097 TI - Designing Theranostic Agents Based on Pluronic Stabilized Gold Nanoaggregates Loaded with Methylene Blue for Multimodal Cell Imaging and Enhanced Photodynamic Therapy. AB - At present, multifunctional noble metal-based nanocomposites are extensively investigated for their potential in performing cellular imaging, diagnostics, and therapy by integration of unique plasmonic properties with the spectroscopic expression and therapeutic activity of appropriate drug. In this work, we report the fabrication of 3-dimensional (3-D) close-packed nanoassemblies of gold nanoparticles by controlling the aggregation of individual nanoparticles in solution and subsequent stabilization of formed aggregates by Pluronic block copolymer (F127) coating. Besides conferring high stability, Pluronic mediates the loading of Methylene Blue (MB) molecules which exhibit interesting spectroscopic and photochemical properties to be employed as both optical label and photosensitizing drug. Indeed, here we demonstrate the pertinence of the fabricated nanoassemblies to provide optical imaging of murine colon carcinoma cells (C-26) via both Raman and fluorescence signals collected from MB molecules, specifically by using scanning confocal surface-enhanced resonant raman spectroscopy (SERRS) and fluorescence lifetime imaging microscopy (FLIM) techniques. The specific configuration of as fabricated nanoassemblies allows a small population of MB molecules to be located in very small areas between the aggregated nanoparticles ("hot spots") to provide SERRS signal while the other population remains captured in Pluronic coating and preserves both its fluorescence signal and singlet-oxygen generation capability. Remarkably, we demonstrate an enhanced photodynamic therapeutic activity of MB-loaded gold nanoaggregates against murine colon carcinoma cells (C-26), as compared to the free photosensitizer. To our knowledge, this is the first report on plasmonic nanoplatforms conveying photosensitizing drug into cells to operate as optical label via both SER(R)S and FLIM and to perform enhanced photodynamic therapy. PMID- 26151098 TI - Characterization of running with compliant curved legs. AB - Running with compliant curved legs involves the progression of the center of pressure, the changes of both the leg's stiffness and effective rest length, and the shift of the location of the maximum stress point along the leg. These phenomena are product of the geometric and material properties of these legs, and the rolling motion produced during stance. We examine these aspects with several reduced-order dynamical models to relate the leg's design parameters (such as normalized foot radius, leg's effective stiffness, location of the maximum stress point and leg shape) to running performance (such as robustness and efficiency). By using these models, we show that running with compliant curved legs can be more efficient, robust with fast recovery behavior from perturbations than running with compliant straight legs. Moreover, the running performance can be further improved by tuning these design parameters in the context of running with rolling. The results shown in this work may serve as potential guidance for future compliant curved leg designs that may further improve the running performance. PMID- 26151099 TI - The induction of Per1 expression by the combined treatment with glutamate, 5 hydroxytriptamine and dopamine initiates a ripple effect on Bmal1 and Cry1 mRNA expression via the ERK signaling pathway in cultured rat spinal astrocytes. AB - Clock genes contribute to the regulation of spinal cord astrocytic function. Although it was previously found that noradrenaline has a pivotal role in the regulation of clock genes expression in cultured rat spinal astrocytes, it is still unknown whether other neurotransmitters might affect clock gene expression. Thus, the effect of spinal neurotransmitters glutamate (Glu), 5-hydroxytriptamine (5-HT) and dopamine (DA) on clock genes expression was examined in cultured rat spinal astrocytes. Simultaneous treatment with Glu (100 MUM), 5-HT (10 MUM) and DA (10 MUM) led to a transient induction of Per1 expression, and a delayed increase of Bmal1 expression and a decrease of Cry1 expression. By contrast, treatment with either Glu, 5-HT or DA alone increased only Per1 expression. The increase in Per1 mRNA by simultaneous treatment with Glu, 5-HT and DA was dependent on extracellular signal-regulated kinase (ERK) activation, since pretreatment with ERK inhibitor U0126 (3 MUM) blocked Per1 expression. Second messengers p38 and c-jun N-terminal kinase were not involved in the neurotransmitter effect on Per1 expression, since pretreatment with SB202190 (3 MUM) and SP600125 (10 MUM), a p38 inhibitor and c-jun N-terminal kinase inhibitor, respectively, had no effect. Blockade of ERK signaling also prevented changes in Bmal1 and Cry1 mRNA expression induced by co-treatment with Glu, 5-HT and DA. In addition to modulating clock gene expression, co-treatment with Glu, 5 HT and DA significantly increased ERK1/2 phosphorylation. Per1 expression itself modulates the expression of other clock gene as knockdown of Per1 expression by using short interference RNA significantly blocked the increase of Bmal1 mRNA expression and the decrease of Cry1 mRNA expression. Thus, neurotransmitters Glu, 5-HT and DA regulate spinal astrocytic clock genes mRNA expression through the ERK pathway and Per1 is a key clock gene that likely modulates the oscillation of clock genes thereby regulating astrocytic function. PMID- 26151101 TI - Neural correlates of fixation duration in natural reading: Evidence from fixation related fMRI. AB - A key assumption of current theories of natural reading is that fixation duration reflects underlying attentional, language, and cognitive processes associated with text comprehension. The neurocognitive correlates of this relationship are currently unknown. To investigate this relationship, we compared neural activation associated with fixation duration in passage reading and a pseudo reading control condition. The results showed that fixation duration was associated with activation in oculomotor and language areas during text reading. Fixation duration during pseudo-reading, on the other hand, showed greater involvement of frontal control regions, suggesting flexibility and task dependency of the eye movement network. Consistent with current models, these results provide support for the hypothesis that fixation duration in reading reflects attentional engagement and language processing. The results also demonstrate that fixation-related fMRI provides a method for investigating the neurocognitive bases of natural reading. PMID- 26151100 TI - Reference-free removal of EEG-fMRI ballistocardiogram artifacts with harmonic regression. AB - Combining electroencephalogram (EEG) recording and functional magnetic resonance imaging (fMRI) offers the potential for imaging brain activity with high spatial and temporal resolution. This potential remains limited by the significant ballistocardiogram (BCG) artifacts induced in the EEG by cardiac pulsation related head movement within the magnetic field. We model the BCG artifact using a harmonic basis, pose the artifact removal problem as a local harmonic regression analysis, and develop an efficient maximum likelihood algorithm to estimate and remove BCG artifacts. Our analysis paradigm accounts for time frequency overlap between the BCG artifacts and neurophysiologic EEG signals, and tracks the spatiotemporal variations in both the artifact and the signal. We evaluate performance on: simulated oscillatory and evoked responses constructed with realistic artifacts; actual anesthesia-induced oscillatory recordings; and actual visual evoked potential recordings. In each case, the local harmonic regression analysis effectively removes the BCG artifacts, and recovers the neurophysiologic EEG signals. We further show that our algorithm outperforms commonly used reference-based and component analysis techniques, particularly in low SNR conditions, the presence of significant time-frequency overlap between the artifact and the signal, and/or large spatiotemporal variations in the BCG. Because our algorithm does not require reference signals and has low computational complexity, it offers a practical tool for removing BCG artifacts from EEG data recorded in combination with fMRI. PMID- 26151102 TI - Verbal and nominal agreement: An fMRI study. AB - Agreement computation is one of the pillars of language comprehension. In this fMRI study, we investigated the neuro-cognitive processes of agreement associated with number feature covariance in subject-verb agreement and determiner-noun concord in Spanish by creating mismatches (ella/*ellas corre, she/*they dances vs. el/*los anillo, thesg/*thepl ring). The results evidenced the engagement of a common bilateral fronto-parietal monitoring system, not language specific, and a left fronto-temporal system that seems to be specifically related to different aspects of phrase and sentence processing. In particular, the major difference was found in the anterior portion of the left MTG-STG, which we relate to fine grained syntactic-combinatorial building mechanisms apparently controlled by the pars opercularis within the LIFG. These results suggest that general conflict monitoring processes operate in parallel with language-specific mechanisms that are sensitive to the specificity of agreement type for the detection of feature covariance among sentence constituents. Specifically, the coupling between these frontal and temporal regions seems to be flexible enough to show sensitivity to the fine-grained combinatorial mechanisms that underlie nominal and subject-verb agreement. PMID- 26151103 TI - Decomposition of brain diffusion imaging data uncovers latent schizophrenias with distinct patterns of white matter anisotropy. AB - Fractional anisotropy (FA) analysis of diffusion tensor-images (DTI) has yielded inconsistent abnormalities in schizophrenia (SZ). Inconsistencies may arise from averaging heterogeneous groups of patients. Here we investigate whether SZ is a heterogeneous group of disorders distinguished by distinct patterns of FA reductions. We developed a Generalized Factorization Method (GFM) to identify biclusters (i.e., subsets of subjects associated with a subset of particular characteristics, such as low FA in specific regions). GFM appropriately assembles a collection of unsupervised techniques with Non-negative Matrix Factorization to generate biclusters, rather than averaging across all subjects and all their characteristics. DTI tract-based spatial statistics images, which output is the locally maximal FA projected onto the group white matter skeleton, were analyzed in 47 SZ and 36 healthy subjects, identifying 8 biclusters. The mean FA of the voxels of each bicluster was significantly different from those of other SZ subjects or 36 healthy controls. The eight biclusters were organized into four more general patterns of low FA in specific regions: 1) genu of corpus callosum (GCC), 2) fornix (FX)+external capsule (EC), 3) splenium of CC (SCC)+retrolenticular limb (RLIC)+posterior limb (PLIC) of the internal capsule, and 4) anterior limb of the internal capsule. These patterns were significantly associated with particular clinical features: Pattern 1 (GCC) with bizarre behavior, pattern 2 (FX+EC) with prominent delusions, and pattern 3 (SCC+RLIC+PLIC) with negative symptoms including disorganized speech. The uncovered patterns suggest that SZ is a heterogeneous group of disorders that can be distinguished by different patterns of FA reductions associated with distinct clinical features. PMID- 26151104 TI - Auditory intensity processing: Categorization versus comparison. AB - Intensity is an important parameter for the perception of complex auditory stimuli like speech. The results of previous studies on the processing of intensity are diverse since left-lateralized, right-lateralized and non lateralized processing was suggested. A clear dependence of the lateralization on the kind of stimuli and/or task is not apparent. With the present functional magnetic resonance imaging (fMRI) study, we directly investigated the differences between a categorical and comparative task. To determine hemispheric involvement we used a method with contralateral noise presentation. Harmonic complexes were presented monaurally without and with contralateral noise. Both categorization and comparison of harmonic complexes according to their intensity more strongly involved the left than the right auditory cortex shown by a stronger effect of the additional noise on the activity in the left auditory cortex. Together with previous results, this suggests that left-lateralized processing of intensity in the auditory cortex can be observed independent of task and stimuli. The comparison task more strongly engaged the left auditory cortex than the categorization task probably due the additional need for sequential comparison and the right auditory cortex probably due to capacity reasons. Comparison also more strongly engaged areas associated with attentional processes and areas responsible for motor response selection. We suggest this to be caused by a more difficult response selection and by the need for continuous update of information in reference memory during the comparison task. PMID- 26151105 TI - Near-infrared spectroscopy for the detection and quantification of bacterial contaminations in pharmaceutical products. AB - Accurate detection and quantification of microbiological contaminations remains an issue mainly due the lack of rapid and precise analytical techniques. Standard methods are expensive and time-consuming being associated to high economic losses and public health threats. In the context of pharmaceutical industry, the development of fast analytical techniques able to overcome these limitations is crucial and spectroscopic techniques might constitute a reliable alternative. In this work we proved the ability of Fourier transform near infrared spectroscopy (FT-NIRS) to detect and quantify bacteria (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens, Salmonella enterica, Staphylococcus epidermidis) from 10 to 10(8) CFUs/mL in sterile saline solutions (NaCl 0.9%). Partial least squares discriminant analysis (PLSDA) models showed that FT-NIRS was able to discriminate between sterile and contaminated solutions for all bacteria as well as to identify the contaminant bacteria. Partial least squares (PLS) models allowed bacterial quantification with limits of detection ranging from 5.1 to 9 CFU/mL for E. coli and B. subtilis, respectively. This methodology was successfully validated in three pharmaceutical preparations (contact lens solution, cough syrup and topic anti-inflammatory solution) proving that this technique possess a high potential to be routinely used for the detection and quantification of bacterial contaminations. PMID- 26151106 TI - Tri/tetra-block co-polymeric nanocarriers as a potential ocular delivery system of lornoxicam: in-vitro characterization, and in-vivo estimation of corneal permeation. AB - Polymeric micelles that can deliver drug to intended sites of the eye have attracted much scientific attention recently. The aim of this study was to evaluate the aqueous-based formulation of drug-loaded polymeric micelles that hold significant promise for ophthalmic drug delivery. This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly(ethylene oxide)-poly(propylene oxide) for the more effective encapsulation of lornoxicam (LX) as a hydrophobic model drug. The co micellization process of 10% binary systems combining different weight ratios of the highly hydrophilic poloxamers; Synperonic((r)) PE/P84, and Synperonic((r)) PE/F127 and the hydrophobic poloxamine counterpart (Tetronic((r)) T701) was investigated by means of photon correlation spectroscopy and cloud point. The drug-loaded micelles were tested for their solubilizing capacity towards LX. Results showed a sharp solubility increase from 0.0318 mg/mL up to more than 2.34 mg/mL, representing about 73-fold increase. Optimized formulation was selected to achieve maximum drug solubilizing power and clarity with lowest possible particle size, and was characterized by (1)HNMR analysis which revealed complete encapsulation of the drug within the micelles. Further investigations by histopathological and confocal laser studies revealed the non-irritant nature and good corneal penetrating power of the proposed nano-formulation. PMID- 26151107 TI - Inhalable spray-dried formulation of D-LAK antimicrobial peptides targeting tuberculosis. AB - Tuberculosis (TB) is a global disease that is becoming more difficult to treat due to the emergence of multidrug resistant (MDR) Mycobacterium tuberculosis. Inhalable antimicrobial peptides (AMPs) are potentially useful alternative anti TB agents because they can overcome resistance against classical antibiotics, reduce systemic adverse effects, and achieve local targeting. The aims of the current study were to produce inhalable dry powders containing d-enantiomeric AMPs (D-LAK120-HP13 and D-LAK120-A) and evaluate their solid state properties, aerosol performance, and structural conformation. These two peptides were spray dried with mannitol as a bulking agent at three mass ratios (peptide:mannitol 1:99, 1:49, and 1:24) from aqueous solutions. The resultant particles were spherical, with those containing D-LAK120-HP13 being more corrugated than those with D-LAK120-A. The median volumetric diameter of the particles was approximately 3MUm. The residual water content of all powders were <3% w/w and crystalline, due to the low hygroscopicity and crystallinity of mannitol, respectively. The mannitol changed from a mixture of alpha- and beta-forms to delta form with an increasing proportion of AMP in the formulation. The emitted fraction and fine particle fraction of the powders when dispersed from an Osmohaler((r)) at 90L/min were about 80% and 50-60% of the loaded dose, respectively, indicating good aerosol performance. Circular dichroism data showed that D-LAK120-HP13 dissolved in Tris buffer at pH 7.15 was of a disordered conformation. In contrast, D-LAK120-A showed greater alpha-helical conformation. Since the conformations of the AMPs were comparable to the controls (unprocessed peptides), the spray drying process did not substantially affect their secondary structures. In conclusion, spray dried powders containing d-enantiomeric AMPs with preserved secondary molecular structures and good aerosol performance could be successfully produced. They may potentially be used for treating MDR-TB when delivered by inhalation. PMID- 26151108 TI - Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients. AB - BACKGROUND: Treatment with vitamin K antagonists is associated with increased morbidity and mortality. Reversal therapy with prothrombin complex concentrate (PCC) is used increasingly and is recommended in the treatment of patients with bleeding complications undertaking surgical interventions, as well as patients at high risk of bleeding. Evidence is lacking regarding indication, dosing, efficacy and safety. OBJECTIVES: We assessed the benefits and harms of PCC compared with fresh frozen plasma in the acute medical and surgical setting involving vitamin K antagonist-treated bleeding and non-bleeding patients. We investigated various outcomes and predefined subgroups and performed sensitivity analysis. We examined risks of bias and applied trial sequential analyses (TSA) to examine the level of evidence, and we prepared a 'Risk of bias' table to test the quality of the evidence. SEARCH METHODS: We searched the following databases from inception to 1 May 2013: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid SP); EMBASE (Ovid SP); International Web of Science; Latin American and Caribbean Health Sciences Literature (LILACS) (via BIREME); the Chinese Biomedical Literature Database; advanced Google and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We applied a systematic and sensitive search strategy to identify relevant randomized clinical trials and imposed no language or date restrictions. We adapted our MEDLINE search strategy for searches in all other databases. We reran the search in October 2014 and found one potential new study of interest. We added this study to a list of 'Studies awaiting classification', and we will incorporate this study into the formal review findings at the time of the review update. SELECTION CRITERIA: We included randomized controlled trials (RCTs), irrespective of publication status, date of publication, blinding status, outcomes published or language. We contacted investigators and study authors to request relevant data. DATA COLLECTION AND ANALYSIS: Three review authors independently abstracted data and resolved disagreements by discussion. Our primary outcome measures were 'overall mortality longest follow-up' and 'overall 28-day mortality'. We performed subgroup analyses to assess the effects of PCC in adults in terms of various clinical and physiological outcomes. We presented pooled estimates of the effects of interventions on dichotomous outcomes as risk ratios (RRs), and on continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We assessed risk of bias by assessing trial methodological components and risk of random error through TSA. MAIN RESULTS: We included four RCTs with a total of 453 participants and determined that none of these trials had overall low risk of bias. We found six ongoing trials from which we were unable to retrieve further data. Three trials provided data on mortality. Meta-analysis showed no statistical effect on overall mortality (RR 0.93, 95% CI 0.37 to 2.33; very low quality of evidence). We were unable to associate use of PCC with the number of complications probably related to the intervention (RR 0.92, 95% CI 0.78 to 1.09; very low quality of evidence). Lack of transfusion data and apparent differences in study design prevented review authors from finding a beneficial effect of PCC in reducing the volume of fresh frozen plasma (FFP) transfused to reverse the effect of vitamin K antagonist treatment. The number of new occurrences of transfusion of red blood cells (RBCs) did not seem to be associated with the use of PCC (RR 1.08, 95% CI 0.82 to 1.43; very low quality of evidence). Still, the included studies demonstrate the possibility of equally reversing vitamin K induced coagulopathy using PCC without the need for transfusion of FFP. No effect on other predefined outcomes was observed. AUTHORS' CONCLUSIONS: In the four included RCTs, use of prothrombin complex concentrate does not appear to reduce mortality or transfusion requirements but demonstrates the possibility of reversing vitamin K-induced coagulopathy without the need for transfusion of fresh frozen plasma. All included trials have high risk of bias and are underpowered to detect mortality, benefit or harm. Clinical and statistical heterogeneity is high, and definitions of clinically important outcomes such as adverse events are highly dissimilar between trials. Only weak observational evidence currently supports the use of PCC in vitamin K antagonist-treated bleeding and non-bleeding patients, and the current systematic review of RCTs does not support the routine use of PCC over FFP. Additional high-quality research is urgently needed. PMID- 26151109 TI - Unusual Gd-nitronyl nitroxide antiferromagnetic coupling and slow magnetic relaxation in the corresponding Tb analogue. AB - The lanthanide-radical approach has been applied to construct three isomorphous mononuclear lanthanide complexes [Ln(hfac)3(NIT2-PyOCH3)] (Ln(III) = Gd , Tb , Er ) in which the nitronyl nitroxide radical NIT2-PyOCH3 (NIT2-PyOCH3 = 2-(3' methoxy-2'-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) acts as a tridentate chelating ligand via the pyridyl nitrogen atom, the oxygen atom from the NO group and the oxygen atom from the methoxy group. The central lanthanide ions are nine-coordinated and their coordination geometry can be considered as an intermediate between muffin and spherical capped square antiprisms. Interestingly, an unusual antiferromagnetic interaction was observed between the Gd(iii) and the coordinated nitronyl nitroxide radical in complex . Moreover, ac magnetic susceptibilities display frequency-dependent out-of-phase signals in the case of the anisotropic Tb complex, indicating magnetic relaxation behavior. PMID- 26151110 TI - Nanometer-thick hyaluronic acid self-assemblies with strong adhesive properties. AB - The adhesive characteristics of poly(allylamine hydrochloride) (PAH)/hyaluronic acid (HA) self-assemblies were investigated using contact adhesion testing. Poly(dimethylsiloxane) spheres and silicon wafers were coated with layer-by-layer (LbL) assemblies of PAH/HA. No increase in adhesion was observed when surfaces covered with dried LbL films were placed in contact. However, bringing the coated surfaces in contact while wet and separating them after drying resulted in an increase by a factor of 100 in the work of adhesion (from one to three bilayers). Herein we discuss the adhesion in PAH/HA and PAH/poly(acrylic acid) assemblies. PAH/HA assemblies have potential application as strong biomedical adhesives. PMID- 26151111 TI - Combinational treatment with microRNA-133b and cetuximab has increased inhibitory effects on the growth and invasion of colorectal cancer cells by regulating EGFR. AB - Colorectal cancer (CRC) is the third most common cancer with a very poor prognosis predominantly due to its high rate of tumor invasion and migration, and its resistance to anti-epidermal growth factor receptor (EGFR) therapy. Although CRC has been widely studied, the underlying molecular mechanism remains to be elucidated. MicroRNA (miR)-133b has been demonstrated to act as a tumor suppressor in several human cancer types by regulating EGFR. However, the detailed involvement of miR-133b and EGFR in CRC cells remain to be elucidated. The present study used reverse transcription quantitative polymerase chain reaction and characterized the downregulation of the expression levels of miR 133b in CRC tissues and cell lines. Cell functional assays demonstrated that restored expression of miR-133b inhibited the growth and invasion of CRC cells. In addition, a luciferase reporter assay revealed that miR-133b directly targeted EGFR and repressed its expression levels in CRC cells. Additionally, combination treatment with miR-133b mimics and the monoclonal anti-EGFR antibody, cetuximab, which is approved and frequently used for treating patients with CRC, exhibited improved inhibitory effects on the growth and invasion of CRC cells compared with treatment with either alone. Taken together, the present study characterized the role of the miR-133b/EGFR interaction in CRC cells and this suggested the combinational therapy with cetuximab and miR-133b was positive and may be a potential novel treatment for patients with CRC in the future. PMID- 26151112 TI - Post-Synthetic Shaping of Porosity and Crystal Structure of Ln-Bipy-MOFs by Thermal Treatment. AB - The reaction of anhydrous lanthanide chlorides together with 4,4'-bipyridine yields the MOFs 2infinity[Ln2Cl6(bipy)3].2bipy, with Ln = Pr - Yb, bipy = 4,4' bipyridine, and 3infinity[La2Cl6(bipy)5].4bipy. Post-synthetic thermal treatment in combination with different vacuum conditions was successfully used to shape the porosity of the MOFs. In addition to the MOFs microporosity, a tuneable mesoporosity can be implemented depending on the treatment conditions as a surface morphological modification. Furthermore, thermal treatment without vacuum results in several identifiable crystalline high-temperature phases. Instead of collapse of the frameworks upon heating, further aggregation under release of bipy is observed. 3infinity[LaCl3(bipy)] and 2infinity[Ln3Cl9(bipy)3], with Ln = La, Pr, Sm, and 1infinity[Ho2Cl6(bipy)2] were identified and characterized, which can also exhibit luminescence. Besides being released upon heating, the linker 4,4'-bipyridine can undergo activation of C-C bonding in ortho-position leading to the in-situ formation of 4,4':2',2'':4'',4'''-quaterpyridine (qtpy). qtpy can thereby function as linker itself, as shown for the formation of the network 2infinity[Gd2Cl6(qtpy)2(bipy)2].bipy. Altogether, the manuscript elaborates the influence of thermal treatment beyond the usual activation procedures reported for MOFs. PMID- 26151113 TI - Antioxidative and Anticanceric Activities of Magnolia (Magnolia denudata) Flower Petal Extract Fermented by Pediococcus acidilactici KCCM 11614. AB - In this study, the effects of magnolia (Magnolia (M.) denudata) extract fermentation in increasing the extract's antioxidative and anticancer activities were investigated. Magnolia was fermented by Pediococcus acidilactici KCCM 11614. The total phenolic content was determined by the Folin-Ciocalteu's method and the antioxidative effects by 1,1-diphenyl-2-picrylhydrazy (DPPH) and ferric reducing ability of plasma (FRAP) assay. Anticancer activity against cancer and normal cells was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Total phenolic content during fermentation increased from 38.1 to 47.0 mg gallic acid equivalent (GAE)/g of solid matter. The radical scavenging activity was 91.4% after 72 h fermentation. Fermented magnolia's antioxidative effect was threefold higher than that of the (non-fermented) control. Fermentation (48 h) increased anticanceric activity against AGS, LoVo, and MCF-7 cancer cells 1.29- to 1.36-fold compared with that of the control, but did not affect MRC-5 (normal) cells, suggesting that fermented magnolia could be used as a natural antioxidative and anticancer agent. PMID- 26151114 TI - Biofunctional Constituents from Michelia compressa var. lanyuensis with Anti Melanogenic Properties. AB - Seven compounds were extracted and purified from the roots of Michelia compressa var. lanyuensis. These compounds are liriodenine, (-)-N-acetylanonaine, pressalanine A, p-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, (-) bornesitol and beta-sitostenone. These compounds were screened for anti proliferation and anti-tyrosinase activities in B16F10 cells. Liriodenine, pressalanine A, (-)-bornesitol and beta-sitostenone displayed cytotoxicity at high concentration (100 MUM), but liriodenine (5 MUM), (-)-N-acetylanonaine (10 MUM), and beta-sitostenone (5 MUM) inhibit tyrosinase activity and reduce the melanin content in B16F10 cells without cytotoxicity, suggesting that liriodenine and beta-sitostenone could be safe and potentially used in cosmetic skin whitening. PMID- 26151115 TI - Novel Fluorinated Phosphorus-Sulfur Heteroatom Compounds: Synthesis and Characterization of Ferrocenyl- and Aryl-Phosphonofluorodithioic Salts, Adducts, and Esters. AB - A series of novel ferrocenyl- and aryl-phosphonofluorodithioic salts, adducts, and esters has been prepared. The reaction of 2,4-diferrocenyl-1,3,2,4 diathiadiphosphetane 2,4-disulfide {[FcP(MU-S)S]2, FcLR} with dry KF or tetrabutylammonium fluoride (TBAF) led to the corresponding potassium and tetrabutylammonium salts of ferrocenyldithiofluorophosphinic acids. Treating potassium ferrocenyldithiofluorophosphinic acid with an equimolar amount of tetraphenylphosphonium chloride readily yielded the corresponding organic adducts, and with mono- and di-halogenated alkanes generated a series of the corresponding esters of ferrocenylphosphonofluoridodithioates. Similarly, using 1,3-epithionaphtho[1,8-cd][1,2,6] oxadiphosphinine 1,3-disulfide or Belleau's Reagent in place of FcLR resulted in the corresponding novel salts, adducts, and ester derivatives. All new compounds have been characterized by means of multi NMR (1H, 13C, 31P, 19F) spectroscopy and accurate mass measurement in conjunction with single crystal X-ray crystallography of four structures. PMID- 26151116 TI - Enzyme Inhibitory Radicinol Derivative from Endophytic fungus Bipolaris sorokiniana LK12, Associated with Rhazya stricta. AB - Endophytes, living inside plant tissues, play an essential role in plant growth and development, whilst producing unique bioactive secondary metabolites. In the current study, the endophytic fungus Bipolaris sorokiniana LK12 was isolated from the leaves of ethno-medicinal and alkaloidal rich Rhazya stricta. The bulk amount of ethyl acetate extract of fungus was subjected to advance column chromatographic techniques, which resulted in the isolation of a new radicinol derivative, bipolarisenol (1). It was found to be a derivative of radicinol. The structure elucidation was carried out by the combined use of 1D and 2D nuclear magnetic resonance, infrared spectroscopy, mass, and UV spectrometric analyses. The bipolarisenol was assessed for its potential role in enzyme inhibition of urease and acetyl cholinesterase (AChE). Results showed that bipolarisenol significantly inhibited the AChE activity with low IC50 (67.23 +/- 5.12 ug.mL-1). Bipolarisenol inhibited urease in a dose-dependent manner with high IC50 (81.62 +/- 4.61 ug.mL-1). The new compound also showed a moderate anti-lipid peroxidation potential (IC50 = 168.91 +/- 4.23 ug.mL-1). In conclusion, endophytes isolated from medicinal plants possess a unique potential to be considered for future drug discovery. PMID- 26151117 TI - Qualitative and Quantitative Analysis of Phenolic Acids, Flavonoids and Iridoid Glycosides in Yinhua Kanggan Tablet by UPLC-QqQ-MS/MS. AB - A simple, rapid and specific ultra-performance liquid chromatography-triple quadrupole mass spectrometry method was developed for the analysis of 29 bioactive components (10 phenolic acids, 16 flavonoids, and three iridoid glycosides) in Yinhua Kanggan tablet (YHKGT), a herbal prescription used for treating upper respiratory infections, fevers, coughs and pharyngalgia. The separation was successfully achieved using a Waters Cortecs UPLC C18 column (50 * 2.1 mm, 1.6 MUm) and gradient elution with water-0.1% formic acid and acetonitrile. Polarity switching mode was used in the optimization of multiple reaction monitoring conditions. The analytical method was validated for linearity, precision and accuracy. Calibration curves for the 29 marker compounds showed good linear regression (r > 0.9982). The limits of detection (LOD) and limits of quantification (LOQ) for the 29 analytes were in the range of 0.03-4.99 ng/mL and 0.16-14.87 ng/mL, respectively. The relative standard deviation (RSD) values of intra-day precision, inter-day precision, repeatability, and stability were less than 2.79%, 4.87%, 4.18% and 4.71%, respectively. The recoveries of the 29 marker compounds were in the range of 94.67%-104.78% (RSD <= 4.72%). These results have shown that this developed method was efficient for the quality evaluation of YHKGT. PMID- 26151118 TI - Light-Induced Infrared Difference Spectroscopy in the Investigation of Light Harvesting Complexes. AB - Light-induced infrared difference spectroscopy (IR-DS) has been used, especially in the last decade, to investigate early photophysics, energy transfer and photoprotection mechanisms in isolated and membrane-bound light harvesting complexes (LHCs). The technique has the definite advantage to give information on how the pigments and the other constituents of the biological system (proteins, membranes, etc.) evolve during a given photoreaction. Different static and time resolved approaches have been used. Compared to the application of IR-DS to photosynthetic Reaction Centers (RCs), however, IR-DS applied to LHCs is still in an almost pioneering age: very often sophisticated techniques (step-scan FTIR, ultrafast IR) or data analysis strategies (global analysis, target analysis, multivariate curve resolution) are needed. In addition, band assignment is usually more complicated than in RCs. The results obtained on the studied systems (chromatophores and RC-LHC supercomplexes from purple bacteria; Peridinin Chlorophyll-a-Proteins from dinoflagellates; isolated LHCII from plants; thylakoids; Orange Carotenoid Protein from cyanobacteria) are summarized. A description of the different IR-DS techniques used is also provided, and the most stimulating perspectives are also described. Especially if used synergically with other biophysical techniques, light-induced IR-DS represents an important tool in the investigation of photophysical/photochemical reactions in LHCs and LHC containing systems. PMID- 26151119 TI - Protective Effect of Procyanidin B2 against CCl4-Induced Acute Liver Injury in Mice. AB - Procyanidin B2 has demonstrated several health benefits and medical properties. However, its protective effects against CCl4-induced hepatotoxicity have not been clarified. The present study aimed to investigate the hepatoprotective effects of procyanidin B2 in CCl4-treated mice. Our data showed that procyanidin B2 significantly decreased the CCl4-induced elevation of serum alanine aminotransferase activities, as well as improved hepatic histopathological abnormalities. Procyanidin B2 also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD, CAT and GSH-Px. Further research demonstrated that procyanidin B2 decreased the expression of TNF-alpha, IL-1beta, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as inhibited the translocation of nuclear factor-kappa B (NF-kappaB) p65 from the cytosol to the nuclear fraction in mouse liver. Moreover, CCl4-induced apoptosis in mouse liver was measured by (terminal-deoxynucleotidyl transferase mediated nick end labeling) TUNEL assay and the cleaved caspase-3. Meanwhile, the expression of apoptosis-related proteins Bax and Bcl-xL was analyzed by Western blot. Results showed that procyanidin B2 significantly inhibited CCl4-induced hepatocyte apoptosis, markedly suppressed the upregulation of Bax expression and restored the downregulation of Bcl-xL expression. Overall, the findings indicated that procyanidin B2 exhibited a protective effect on CCl4-induced hepatic injury by elevating the antioxidative defense potential and consequently suppressing the inflammatory response and apoptosis of liver tissues. PMID- 26151120 TI - Objectively measured physical activity is associated with parameters of bone in 70-year-old men and women. AB - As the world's population ages, the occurrence of osteoporosis-related fractures is projected to increase. Low areal bone mineral density (aBMD), a well-known risk factor for fractures, may be influenced by physical activity (PA). In this cross-sectional study, we aimed to investigate potential associations between objective measures of PA and bone properties, in a population-based cohort of 1228 70-year-old men and women. We measured volumetric BMD (vBMD, mg/cm(3)) together with cross-sectional area (CSA, mm(2)) by peripheral quantitative computed tomography at sites located 4% and 66% in the distal-proximal trajectory at the tibia and radius. We also measured aBMD (g/cm(2)) by dual energy X-ray absorptiometry at the femoral neck, lumbar spine (L1-L4) and radius. Participants wore triaxial accelerometers for 7 consecutive days to obtain objective estimates of PA. The intensity of the objective PA was divided into light (100-1951 counts/min [CPM]), moderate (1952-5724 cpm) and vigorous (>= 5725 cpm). Maximal accelerations for the anterior-posterior (z), medio-lateral (x), and vertical (y) axes were also separately assessed. Associations were investigated using bivariate correlations and multiple linear regression, adjusted for height, weight and sex. Vigorous PA showed the strongest association with femoral neck aBMD (beta=0.09, p<0.001), while both moderate and vigorous PAs were associated with cortical area and trabecular vBMD in the weight-bearing tibia (all p<0.05). Peak vertical accelerations were associated significantly with cortical area (beta=0.09, p<0.001) and trabecular vBMD (beta=0.09, p=0.001) of the tibia, whereas peak anterior-posterior accelerations showed no correlation with these properties. No positive association was found between objectively measured PA and bone parameters of the radius. In conclusion, vertical accelerations and moderate to vigorous PA independently predict bone properties, especially in the weight bearing tibia, in 70-year-old men and women. PMID- 26151121 TI - Multiscale biomechanical responses of adapted bone-periodontal ligament-tooth fibrous joints. AB - Reduced functional loads cause adaptations in organs. In this study, temporal adaptations of bone-ligament-tooth fibrous joints to reduced functional loads were mapped using a holistic approach. Systematic studies were performed to evaluate organ-level and tissue-level adaptations in specimens harvested periodically from rats (N=60) given powder food for 6 months over 8,12,16,20, and 24 weeks. Bone-periodontal ligament (PDL)-tooth fibrous joint adaptation was evaluated by comparing changes in joint stiffness with changes in functional space between the tooth and alveolar bony socket. Adaptations in tissues included mapping changes in the PDL and bone architecture as observed from collagen birefringence, bone hardness and volume fraction in rats fed soft foods (soft diet, SD) compared to those fed hard pellets as a routine diet (hard diet, HD). In situ biomechanical testing on harvested fibrous joints revealed increased stiffness in SD groups (SD:239-605 N/mm) (p<0.05) at 8 and 12 weeks. Increased joint stiffness in early development phase was due to decreased functional space (at 8 weeks change in functional space was -33 MUm, at 12 weeks change in functional space was -30 MUm) and shifts in tissue quality as highlighted by birefringence, architecture and hardness. These physical changes were not observed in joints that were well into function, that is, in rodents older than 12 weeks of age. Significant adaptations in older groups were highlighted by shifts in bone growth (bone volume fraction 24 weeks: Delta-0.06) and bone hardness (8 weeks: Delta-0.04 GPa, 16 weeks: Delta-0.07 GPa, 24 weeks: Delta-0.06 GPa). The response rate (N/s) of joints to mechanical loads decreased in SD groups. Results from the study showed that joint adaptation depended on age. The initial form-related adaptation (observed change in functional space) can challenge strain-adaptive nature of tissues to meet functional demands with increasing age into adulthood. The coupled effect between functional space in the bone-PDL-tooth complex and strain-adaptive nature of tissues is necessary to accommodate functional demands, and is temporally sensitive despite joint malfunction. From an applied science perspective, we propose that adaptations are registered as functional history in tissues and joints. PMID- 26151122 TI - Parathyroid hormone regulation of hypoxia-inducible factor signaling in osteoblastic cells. AB - Osteoblasts perceive and respond to changes in their pericellular environment, including biophysical signals and oxygen availability, to elicit an anabolic or catabolic response. Parathyroid hormone (PTH) affects each arm of skeletal remodeling, with net anabolic or catabolic effects dependent upon duration of exposure. Similarly, the capacity of osteoblastic cells to perceive pericellular oxygen has a profound effect on skeletal mass and architecture, as mice expressing stable hypoxia-inducible factor (HIF)-1alpha and -2alpha demonstrate age-dependent increases in bone volume per tissue volume and osteoblast number. Further, HIF levels and signaling can be influenced in an oxygen-independent manner. Because the cellular mechanisms involved in PTH regulation of the skeleton remain vague, we sought whether PTH could influence HIF-1alpha expression and HIF-alpha-driven luciferase activity independently of altered oxygen availability. Using UMR106.01 mature osteoblasts, we observed that 100nM hPTH(1-34) decreased HIF-1alpha and HIF-responsive luciferase activity in a process involving heat shock protein 90 (Hsp90) and cyclic AMP but not intracellular calcium. Altering activity of the small GTPase RhoA and its effector kinase ROCK altered HIF-alpha-driven luciferase activity in the absence and presence of PTH. Taken together, these data introduce PTH as a regulator of oxygen-independent HIF-1alpha levels through a mechanism involving cyclic AMP, Hsp90, and the cytoskeleton. PMID- 26151123 TI - Correlation of hip fracture with other fracture types: Toward a rational composite hip fracture endpoint. AB - PURPOSE: With ethical requirements to the enrollment of lower risk subjects, osteoporosis trials are underpowered to detect reduction in hip fractures. Different skeletal sites have different levels of fracture risk and response to treatment. We sought to identify fracture sites which cluster with hip fracture at higher than expected frequency; if these sites respond to treatment similarly, then a composite fracture endpoint could provide a better estimate of hip fracture reduction. METHODS: Cohort study using Veterans Affairs and Medicare administrative data. Male Veterans (n=5,036,536) aged 50-99 years receiving VA primary care between 1999 and 2009 were included. Fractures were ascertained using ICD9 and CPT codes and classified by skeletal site. Pearson correlation coefficients, logistic regression and kappa statistics were used to describe the correlation between each fracture type and hip fracture within individuals, without regard to the timing of the events. RESULTS: 595,579 (11.8%) men suffered 1 or more fractures and 179,597 (3.6%) suffered 2 or more fractures during the time under study. Of those with one or more fractures, the rib was the most common site (29%), followed by spine (22%), hip (21%) and femur (20%). The fracture types most highly correlated with hip fracture were pelvic/acetabular (Pearson correlation coefficient 0.25, p<0.0001), femur (0.15, p<0.0001), and shoulder (0.11, p<0.0001). CONCLUSIONS: Pelvic, acetabular, femur, and shoulder fractures cluster with hip fractures within individuals at greater than expected frequency. If we observe similar treatment risk reductions within that cluster, subsequent trials could consider the use of a composite endpoint to better estimate hip fracture risk. PMID- 26151124 TI - Corrigendum: DNA methylation signatures link prenatal famine exposure to growth and metabolism. PMID- 26151125 TI - Applicability of the polynomial chaos expansion method for personalization of a cardiovascular pulse wave propagation model. PMID- 26151126 TI - A secretomic study on human hepatocellular carcinoma multiple drug-resistant cell lines. AB - The aim of this study was to identify pivotal dysregulated proteins that are biomarkers for multiple drug resistance (MDR) of human hepatocellular carcinoma (HCC). The secretome profiles of the human HCC MDR cell line BEL7402/5-FU and its parental cell line BEL7402 were comparatively analyzed using isobaric tags for the relative and absolute quantification (iTRAQ)-coupled 2D LC-MS/MS. In total, 279 differentially expressed proteins were identified, of which, with a consistent result in the duplex test, 131 proteins were overexpressed in BEL7402/5-FU compared to its parental cell line, and 56 proteins were underexpressed. Several differentially expressed proteins determined by western blot analysis were also validated. The association of MDR with one of the highly regulated proteins, alpha-2-HS-glycoprotein (AHSG) was determined. This study detailed the application of iTRAQ technology to MDR biomarkers in the HCC cell secretome. The results showed that differentially expressed proteins that may be associated with MDR of HCC provide valuable additional information with regard to understanding the role of MDR. PMID- 26151128 TI - Downregulation of microRNA-146a inhibits ovarian granulosa cell apoptosis by simultaneously targeting interleukin-1 receptor-associated kinase and tumor necrosis factor receptor-associated factor 6. AB - Premature ovarian failure (POF), an ovarian disorder of multifactorial origin, is defined as the occurrence of amenorrhea, hypergonadotropism and hypoestrogenism in females <40 years old. Apoptosis of ovarian granulosa cells is important in POF and understanding the regulatory mechanism underlying ovarian granulosa cell apoptosis may be beneficial for the management of POF. Increasing evidence suggests that microRNAs (miRs) have a regulatory function in oocyte maturation and ovarian follicular development. In the present study, the expression of miR 146a in plasma and ovarian granulosa cells obtained from patients with POF, its effect on the apoptosis of ovarian granulosa cells and the possible underlying mechanisms were examined. The present study demonstrated that compared with the control groups, the expression of miR-146a in the plasma and in ovarian granulosa cells of patients with POF was significantly upregulated. Furthermore, it was found that miR-146a simultaneously targeted interleukin-1 receptor-associated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), which regulated the activity of nuclear factor-kappaB and IkappaBalpha. In addition, the results demonstrated that inhibition of the caspase cascade by caspase inhibitors attenuated the effects of miR-146a on ovarian granulosa cell apoptosis. Taken together, these results suggest that miR-146a has an important promoting effect on the apoptosis of granulosa cells by targeting IRAK1 and TRAF6 via the caspase cascade pathway. These results may be useful for the management of POF. PMID- 26151127 TI - Probing the target search of DNA-binding proteins in mammalian cells using TetR as model searcher. AB - Many cellular functions rely on DNA-binding proteins finding and associating to specific sites in the genome. Yet the mechanisms underlying the target search remain poorly understood, especially in the case of the highly organized mammalian cell nucleus. Using as a model Tet repressors (TetRs) searching for a multi-array locus, we quantitatively analyse the search process in human cells with single-molecule tracking and single-cell protein-DNA association measurements. We find that TetRs explore the nucleus and reach their target by 3D diffusion interspersed with transient interactions with non-cognate sites, consistent with the facilitated diffusion model. Remarkably, nonspecific binding times are broadly distributed, underlining a lack of clear delimitation between specific and nonspecific interactions. However, the search kinetics is not determined by diffusive transport but by the low association rate to nonspecific sites. Altogether, our results provide a comprehensive view of the recruitment dynamics of proteins at specific loci in mammalian cells. PMID- 26151129 TI - Selective deuteration for molecular insights into the digestion of medium chain triglycerides. AB - Medium chain triglycerides (MCTs) are a unique form of dietary fat that have a wide range of health benefits. They are molecules with a glycerol backbone esterified with medium chain (6-12 carbon atoms) fatty acids on the two outer (sn 1 and sn-3) and the middle (sn-2) positions. During lipid digestion in the gastrointestinal tract, pancreatic lipase stereoselectively hydrolyses the ester bonds of these triglycerides on the sn-1 and sn-3 positions resulting in sn-2 monoglyceride and fatty acids as major products. However, the sn-2 monoglycerides are thermodynamically less stable than their sn-1/3 counterparts. Isomerization or fatty acid migration from the sn-2 monoglyceride to sn-1/3 monoglyceride may occur spontaneously and would lead to glycerol and fatty acid as final products. Here, tricaprin (C10) with selectively deuterated fatty acid chains was used for the first time to monitor chain migration and the stereoselectivity of the pancreatic lipase-catalyzed hydrolysis of ester bonds. The intermediate and final digestion products were studied using NMR and mass spectrometry under biologically relevant conditions. The hydrolysis of the sn-2 monocaprin to glycerol and capric acid did not occur within biologically relevant timescales and fatty acid migration occurs only in limited amounts as a result of the presence of undigested diglyceride species over long periods of time in the digestion medium. The slow kinetics for the exchange of the sn-2 fatty acid chain and the stereoselectivity of pancreatic lipase on MCTs is relevant for industrial processes that involve enzymatic interesterification and the production of high value products such as specific structured triacylglycerols, confectionery fats and nutritional products. PMID- 26151130 TI - Pectins esterification in the apoplast of aluminum-treated pea root nodules. AB - Aiming to elucidate the possible involvement of pectins in aluminum-mediated growth inhibition the distribution of pectins in the apoplast of root nodules was investigated. Experiments were performed on the pea (Pisum sativum L.) root nodules treated with aluminum (50 MUM AlCl3, for 2 or 24h). For histochemical acidic pectin localization we used ruthenium red staining. Immunolabeling techniques with monoclonal antibodies specific to high methyl-esterified pectin (JIM7), low methyl-esterified pectin (JIM5) and calcium cross-linked pectin (2F4) were used to re-examine the pattern of pectin esterification and distribution. After immunolabeling the samples were observed using a fluorescent and transmission electron microscope. Ruthenium red staining showed that acid pectin content increased in the apoplast of Al-treated nodules and immunolocalization of pectin epitopes revealed that the fraction of de-esterified pectins increased significantly under Al stress. JIM5 and 2F4 epitopes were located on the inner surface of the primary cell wall with higher intensity at cell corners lining the intercellular spaces and at infection threads (ITs) walls. By contrast, JIM 7 labels all walls uniformly throughout the nodule. In the presence of Al, the increase of JIM5 and 2F4 labeling in thick plant and IT walls, together with a decrease of JIM7 labeling was observed. These results indicate a specific role for pectin de-esterification in the process of wall thickening and growth inhibition. In particular, Al-dependent increase in pectin content and their low methyl esterification degree correlate with wall thickness and higher rigidity, and in this way, may affect IT and nodules growth. PMID- 26151131 TI - Professional liability insurance and medical error disclosure. AB - QUESTION UNDER STUDY: To examine medicolegal stakeholders' views about the impact of professional liability insurance in Switzerland on medical error disclosure. METHODS: Purposive sample of 23 key medicolegal stakeholders in Switzerland from a range of fields between October 2012 and February 2013. Data were collected via individual, face-to-face interviews using a researcher-developed semi-structured interview guide. Interviews were transcribed and analysed using conventional content analysis. RESULTS: Participants, particularly those with a legal or quality background, reported that concerns relating to professional liability insurance often inhibited communication with patients after a medical error. Healthcare providers were reported to be particularly concerned about losing their liability insurance cover for apologising to harmed patients. It was reported that the attempt to limit the exchange of information and communication could lead to a conflict with patient rights law. Participants reported that hospitals could, and in some case are, moving towards self-insurance approaches, which could increase flexibility regarding error communication CONCLUSION: The reported current practice of at least some liability insurance companies in Switzerland of inhibiting communication with harmed patients after an error is concerning and requires further investigation. With a new ethic of transparency regarding medical errors now prevailing internationally, this approach is increasingly being perceived to be misguided. A move away from hospitals relying solely on liability insurance may allow greater transparency after errors. Legalisation preventing the loss of liability insurance coverage for apologising to harmed patients should also be considered. PMID- 26151132 TI - Insight into the Spectrum of Coronary Atherosclerosis in Asymptomatic Urban Han Chinese Population by Coronary Computed Tomography Angiography. AB - OBJECTIVES: Highlighted the spectrum of coronary atherosclerosis in asymptomatic population by Computed Tomography Angiography (CTA) and developed a surrogation of expensive CTA to early detect coronary atherosclerosis. METHODS: Three hundred and seven self-referred urban Han Chinese asymptomatic individuals underwent coronary CTA were consecutively enrolled. Total plaque score (TPS), Segment stenosis score (SSS) and Coronary Artery Disease severity (CADS) were used to measure and illustrate the spectrum of atherosclerosis burden by mapping their incidence and proportion onto coronary artery tree. Logistic regression model was further used to explore the association between lipid biomarkers and TPS (SSS) for developing a surrogation of CTA to early detect coronary atherosclerosis. RESULTS: We found that the incidence of TPS, SSS and CADS were up to 71.34%, 68.08%, and 71.34%; and high-risk individuals reached up to 11.07%, 15.31% and 16.29% respectively. All TPS, SSS and CADS were much higher in male than female, and have trend of increasing with age. The most lesion segment emerged on proximal LAD, followed by proximal RCA, mid LAD, proximal LCX, and mid RCA with mixed plaque as dominant. HDL-C was a predictor to both TPS [OR: 0.12 (0.02 0.82)] and SSS [OR: 0.15 (0.03-0.76)], and could identify the serious atherosclerosis subjects of TPS or SSS score >5 (AUC 0.73 and 0.70). CONCLUSIONS: The atherosclerosis plaque burden was about one in ten as high-risk individuals in this specific urban Han Chinese population. As potential surrogation of CTA, HDL-C was recognized as a significant predictor to atherosclerosis burden and revealed a good performance for identifying high-risk individuals. PMID- 26151133 TI - Differential Responses to Food Price Changes by Personal Characteristic: A Systematic Review of Experimental Studies. AB - BACKGROUND: Fiscal interventions to improve population diet have been recommended for consideration by many organisations including the World Health Organisation and the United Nations and policies such as sugar-sweetened beverage taxes have been implemented at national and sub-national levels. However, concerns have been raised with respect to the differential impact of fiscal interventions on population sub-groups and this remains a barrier to implementation. OBJECTIVE: To examine how personal characteristics (such as socioeconomic status, sex, impulsivity, and income) moderate changes in purchases of targeted foods in response to food and beverage price changes in experimental settings. DESIGN: Systematic review. DATA SOURCES: Online databases (PubMed, EMBASE, Web of Science, EconLit and PsycInfo), reference lists of previous reviews, and additional data from study authors. STUDY SELECTION: We included randomised controlled trials where food and beverage prices were manipulated and reported differential effects of the intervention on participant sub-groups defined according to personal characteristics. DATA ANALYSIS: Where possible, we extracted data to enable the calculation of price elasticities for the target foods by personal characteristic. RESULTS: 8 studies were included in the review. Across studies, the difference in price elasticity varied from 0.02 to 2.43 between groups within the same study. 11 out of the total of 18 comparisons of own-price elasticity estimates by personal characteristic differed by more than 0.2 between groups. Income related factors were the most commonly considered and there was an indication that own-price elasticity estimates do vary by income but the direction of this effect was not clear. CONCLUSION: Experimental studies provide an opportunity to examine the differential effects of fiscal measures to improve population diets. Patterns in price sensitivity by personal characteristics are complex. General conclusions pertaining to the effects of personal characteristics on price sensitivity are not supported by the evidence, which shows heterogeneity between studies and populations. TRIAL REGISTRATION: PROSPERO CRD42014009705. PMID- 26151134 TI - Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis. AB - Aneuploidies are prevalent in the human embryo and impair proper development, leading to cell cycle arrest. Recent advances in imaging and molecular and genetic analyses are postulated as promising strategies to unveil the mechanisms involved in aneuploidy generation. Here we combine time-lapse, complete chromosomal assessment and single-cell RT-qPCR to simultaneously obtain information from all cells that compose a human embryo until the approximately eight-cell stage (n=85). Our data indicate that the chromosomal status of aneuploid embryos (n=26), including those that are mosaic (n=3), correlates with significant differences in the duration of the first mitotic phase when compared with euploid embryos (n=28). Moreover, gene expression profiling suggests that a subset of genes is differentially expressed in aneuploid embryos during the first 30 h of development. Thus, we propose that the chromosomal fate of an embryo is likely determined as early as the pronuclear stage and may be predicted by a 12 gene transcriptomic signature. PMID- 26151135 TI - Pharmacokinetics of Active Components of Yokukansan, a Traditional Japanese Herbal Medicine after a Single Oral Administration to Healthy Japanese Volunteers: A Cross-Over, Randomized Study. AB - CONTEXT: Yokukansan (YKS) is a traditional Japanese herbal medicine called kampo medicine in Japan. Its extract comprises seven crude drugs: Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix. YKS is used to treat neurosis, insomnia, as well as behavioral and psychological symptoms of dementia. OBJECTIVE: To confirm the exposure and pharmacokinetics of the active components of YKS in healthy volunteers. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, 3-arm, 3-period, crossover trial was conducted on 21 healthy Japanese volunteers at the Kochi Medical University between May 2012 and November 2012. INTERVENTIONS: Single oral administration of YKS (2.5 g, 5.0 g, or 7.5 g/day) during each period. MAIN OUTCOME MEASURE: Plasma concentrations of three active compounds in YKS, namely 18beta-glycyrrhetinic acid (GA), geissoschizine methyl ether (GM), and hirsuteine (HTE). RESULTS: The mean maximum plasma concentrations (Cmax) of GM and HTE increased dose-dependently (ranges: 0.650-1.98 ng/mL and 0.138-0.450 ng/mL, respectively). The times to maximum plasma concentration after drug administration (tmax) were 0.500 h for GM and 0.975-1.00 h for HTE. The apparent elimination half-lives (t1/2) were 1.72-1.95 h for GM and 2.47-3.03 h for HTE. These data indicate the rapid absorption and elimination of GM and HTE. On the other hand, the Cmax, tmax, and t1/2 of GA were 57.7-108 ng/mL, 8.00-8.01 h, and 9.39-12.3 h, respectively. CONCLUSION: We demonstrated that pharmacologically active components of YKS are detected in humans. Further, we determined the pharmacokinetics of GM, HTE, and GA. This information will be useful to elucidate the pharmacological effects of YKS. TRIAL REGISTRATION: Japan Pharmaceutical Information Center JAPIC CTI-121811. PMID- 26151136 TI - Spore-Forming Thermophilic Bacterium within Artificial Meteorite Survives Entry into the Earth's Atmosphere on FOTON-M4 Satellite Landing Module. AB - One of the key conditions of the lithopanspermia hypothesis is that microorganisms situated within meteorites could survive hypervelocity entry from space through the Earth's atmosphere. So far, all experimental proof of this possibility has been based on tests with sounding rockets which do not reach the transit velocities of natural meteorites. We explored the survival of the spore forming thermophilic anaerobic bacterium, Thermoanaerobacter siderophilus, placed within 1.4-cm thick basalt discs fixed on the exterior of a space capsule (the METEORITE experiment on the FOTON-M4 satellite). After 45 days of orbital flight, the landing module of the space vehicle returned to Earth. The temperature during the atmospheric transit was high enough to melt the surface of basalt. T. siderophilus survived the entry; viable cells were recovered from 4 of 24 wells loaded with this microorganism. The identity of the strain was confirmed by 16S rRNA gene sequence and physiological tests. This is the first report on the survival of a lifeform within an artificial meteorite after entry from space orbit through Earth's atmosphere at a velocity that closely approached the velocities of natural meteorites. The characteristics of the artificial meteorite and the living object applied in this study can serve as positive controls in further experiments on testing of different organisms and conditions of interplanetary transport. PMID- 26151137 TI - Big Data: Astronomical or Genomical? AB - Genomics is a Big Data science and is going to get much bigger, very soon, but it is not known whether the needs of genomics will exceed other Big Data domains. Projecting to the year 2025, we compared genomics with three other major generators of Big Data: astronomy, YouTube, and Twitter. Our estimates show that genomics is a "four-headed beast"--it is either on par with or the most demanding of the domains analyzed here in terms of data acquisition, storage, distribution, and analysis. We discuss aspects of new technologies that will need to be developed to rise up and meet the computational challenges that genomics poses for the near future. Now is the time for concerted, community-wide planning for the "genomical" challenges of the next decade. PMID- 26151140 TI - Reviews. PMID- 26151138 TI - Filtration Device for On-Site Collection, Storage and Shipment of Cells from Urine and Its Application to DNA-Based Detection of Bladder Cancer. AB - Molecular analysis of cells from urine provides a convenient approach to non invasive detection of bladder cancer. The practical use of urinary cell-based tests is often hampered by difficulties in handling and analyzing large sample volumes, the need for rapid sample processing to avoid degradation of cellular content, and low sensitivity due to a high background of normal cells. We present a filtration device, designed for home or point-of-care use, which enables collection, storage and shipment of urinary cells. A special feature of this device is a removable cartridge housing a membrane filter, which after filtration of urine can be transferred to a storage unit containing an appropriate preserving solution. In spiking experiments, the use of this device provided efficient recovery of bladder cancer cells with elimination of >99% of excess smaller-sized cells. The performance of the device was further evaluated by DNA based analysis of urinary cells collected from 57 patients subjected to transurethral resection following flexible cystoscopy indicating the presence of a tumor. All samples were tested for FGFR3 mutations and seven DNA methylation markers (BCL2, CCNA1, EOMES, HOXA9, POU4F2, SALL3 and VIM). In the group of patients where a transitional cell tumor was confirmed at histopathological evaluation, urine DNA was positive for one or more markers in 29 out of 31 cases (94%), including 19 with FGFR3 mutation (61%). In the group of patients with benign histopathology, urine DNA was positive for methylation markers in 13 out of 26 cases (50%). Only one patient in this group was positive for a FGFR3 mutation. This patient had a stage Ta tumor resected 6 months later. The ability to easily collect, store and ship diagnostic cells from urine using the presented device may facilitate non-invasive testing for bladder cancer. PMID- 26151141 TI - Reviews. PMID- 26151142 TI - Reviews. PMID- 26151143 TI - You're the Flight Surgeon. AB - Andrus DE. You're the flight surgeon: sarcoidosis. Aerosp Med Hum Perform. 2015; 86(1):67-69. PMID- 26151144 TI - You're the Flight Surgeon. AB - Govil N. You're the flight surgeon: aviator with brief psychotic episode. Aerosp Med Hum Perform. 2015; 86(1):69-72. PMID- 26151145 TI - This Month in Aerospace Medicine History. PMID- 26151146 TI - Class Size and Student Achievement. PMID- 26151147 TI - Making Lemonade Out of Life's Lemons: A View Into the World of Aging With Parkinson's Disease. AB - Pictures can aid in understanding individual perspectives of an experience. Photovoice, a visual elicitation research approach, was used to engage nine participants with Parkinson's disease in taking photographs that, for them, represented important aspects of living with the disease. Participants' descriptions of their photographs revealed perspectives that can be theoretically linked to two psychosocial stages of development: (a) generativity versus stagnation and (b) integrity versus despair. Clear examples of generativity and integrity were present in participants' responses, reflecting determination and optimism in living with the disease. Findings highlight the need to seek understanding of patients' individual experiences of living with an illness so it is not falsely assumed that they are not adjusting or managing their disease. PMID- 26151148 TI - Psychosocial Effects of Health Disparities of Lesbian, Gay, Bisexual, and Transgender Older Adults. AB - The 1.5 million older adults who self-identify as lesbian, gay, bisexual, and transgender (LGBT) are expected to double in number by 2030. Research suggests that health disparities are closely linked with societal stigma, discrimination, and denial of civil and human rights. More LGBT older adults struggle with depression, substance abuse, social isolation, and acceptance compared to their heterosexual counterparts. Despite individual preferences, most health care providers recognize the right of any individual to have access to basic medical services. The U.S. Department of Health and Human Services requires that all hospitals receiving funds from Medicare and Medicaid respect visitation and medical decision-making rights to all individuals identifying as LGBT. The Joint Commission also requires a non-discrimination statement for accreditation. The current literature review examines LGBT health disparities and the consequential psychosocial impact on LGBT older adults as well as brings awareness to the needs of this underserved and underrepresented population. PMID- 26151149 TI - Improving Employment Outcomes in Assertive Community Treatment (ACT): The Role of the ACT Nurse. AB - Assertive community treatment (ACT) for individuals with serious mental illness is a community-based mental health service model where nurses play a significant leadership role as health and wellness educators and consultants to consumers and fellow staff members. The ACT model was designed to include a vocational focus as an important aspect of community integration. Nevertheless, research suggests that ACT does not assist a significant number of consumers in achieving employment goals. Nurses can play a critical part in the recovery and wellness of individuals receiving ACT services. Individual placement and support principles provide a foundation for implementing employment into current services. PMID- 26151150 TI - Characterization of Adsorbed Alkali Metal Ions in 2:1 Type Clay Minerals from First-Principles Metadynamics. AB - Adsorption states of alkali metal ions in three kinds of 2:1 type clay minerals are systematically investigated via first-principles-based metadynamics. Our reconstructed free energy surfaces in a two-dimensional space of coordination numbers specifically employed as collective variables for describing the interlayer cations show that an inner-sphere (IS) complex is preferentially formed for Cs(+) in the 2:1 type trioctahedral clay minerals with saponite-like compositions, where lighter alkali metal ions show a tendency to form an outer sphere one instead. The strong preference for an IS complex observed for Cs(+) is found to result partially from the capability of recognizing selectively Cs(+) ions at the basal O atoms with the Lewis basicity significantly enhanced by the isomorphic substitution in tetrahedral sheets. PMID- 26151151 TI - A Novel Approach in Quantifying the Effect of Urban Design Features on Local Scale Air Pollution in Central Urban Areas. AB - Differences in urban design features may affect emission and dispersion patterns of air pollution at local-scales within cities. However, the complexity of urban forms, interdependence of variables, and temporal and spatial variability of processes make it difficult to quantify determinants of local-scale air pollution. This paper uses a combination of dense measurements and a novel approach to land-use regression (LUR) modeling to identify key controls on concentrations of ambient nitrogen dioxide (NO2) at a local-scale within a central business district (CBD). Sixty-two locations were measured over 44 days in Auckland, New Zealand at high density (study area 0.15 km(2)). A local-scale LUR model was developed, with seven variables identified as determinants based on standard model criteria. A novel method for improving standard LUR design was developed using two independent data sets (at local and "city" scales) to generate improved accuracy in predictions and greater confidence in results. This revised multiscale LUR model identified three urban design variables (intersection, proximity to a bus stop, and street width) as having the more significant determination on local-scale air quality, and had improved adaptability between data sets. PMID- 26151152 TI - UV-curable nanocomposite based on methacrylic-siloxane resin and surface-modified TiO2 nanocrystals. AB - A novel UV-light-curable nanocomposite material formed of a methacrylic-siloxane resin loaded with 1 wt % oleic acid and 3-(trimethoxysilyl)propyl methacrylate silane (OLEA/MEMO)-coated TiO2 nanorods (NRs) has been manufactured as a potential self-curing structural coating material for protection of monuments and artworks, optical elements, and dental components. OLEA-coated TiO2 NRs, presynthesized by a colloidal chemistry route, have been surface-modified by a treatment with the methacrylic-based silane coupling agent MEMO. The resulting OLEA/MEMO-capped TiO2 NRs have been dispersed in MEMO; that is a monomer precursor of the organic formulation, used as a "common solvent" for transferring the NRs in prepolymer components of the formulation. Differential scanning calorimetry and Fourier transform infrared spectroscopy have allowed investigation of the effects of the incorporation of the OLEA/MEMO-capped TiO2 NRs on reactivity and photopolymerization kinetics of the nanocomposite, demonstrating that the embedded NRs significantly increase curing reactivity of the neat organic formulation both in air and inert atmosphere. Such a result has been explained on the basis of the photoactivity of the nanocrystalline TiO2 which behaves as a free-radical donor photocatalyst in the curing reaction, finally turning out more effective than the commonly used commercial photoinitiator. Namely, the NRs have been found to accelerate the cure rate and increase cross-linking density, promoting multiple covalent bonds between the resin prepolymers and the NR ligand molecules, and, moreover, they limit inhibition effect of oxygen on photopolymerization. The NRs distribute uniformly in the photocurable matrix, as assessed by transmission electron microscopy analysis, and increase glass transition temperature and water contact angle of the nanocomposite with respect to the neat resin. PMID- 26151153 TI - Nitrogen Doping Enables Covalent-Like pi-pi Bonding between Graphenes. AB - The neighboring layers in bilayer (and few-layer) graphenes of both AA and AB stacking motifs are known to be separated at a distance corresponding to van der Waals (vdW) interactions. In this Letter, we present for the first time a new aspect of graphene chemistry in terms of a special chemical bonding between the giant graphene "molecules". Through rigorous theoretical calculations, we demonstrate that the N-doped graphenes (NGPs) with various doping levels can form an unusual two-dimensional (2D) pi-pi bonding in bilayer NGPs bringing the neighboring NGPs to significantly reduced interlayer separations. The interlayer binding energies can be enhanced by up to 50% compared to the pristine graphene bilayers that are characterized by only vdW interactions. Such an unusual chemical bonding arises from the pi-pi overlap across the vdW gap while the individual layers maintain their in-plane pi-conjugation and are accordingly planar. The existence of the resulting interlayer covalent-like bonding is corroborated by electronic structure calculations and crystal orbital overlap population (COOP) analyses. In NGP-based graphite with the optimal doping level, the NGP layers are uniformly stacked and the 3D bulk exhibits metallic characteristics both in the in-plane and along the stacking directions. PMID- 26151154 TI - Luminescent Ce(III) Complexes as Stoichiometric and Catalytic Photoreductants for Halogen Atom Abstraction Reactions. AB - Luminescent Ce(III) complexes, Ce[N(SiMe3)2]3 (1) and [(Me3Si)2NC(RN)2]Ce[N(SiMe3)2]2 (R = (i)Pr, 1-(i)Pr; R = Cy, 1-Cy), with C(3v) and C(2v) solution symmetries display absorptive 4f -> 5d electronic transitions in the visible region. Emission bands are observed at 553, 518, and 523 nm for 1, 1-(i)Pr, and 1-Cy with lifetimes of 24, 67, and 61 ns, respectively. Time dependent density functional theory (TD-DFT) studies on 1 and 1-(i)Pr revealed the (2)A1 excited states corresponded to singly occupied 5d(z(2)) orbitals. The strongly reducing metalloradical character of 1, 1-(i)Pr, and 1-Cy in their (2)A1 excited states afforded photochemical halogen atom abstraction reactions from sp(3) and sp(2) C-X (X = Cl, Br, I) bonds for the first time with a lanthanide cation. The dehalogenation reactions could be turned over with catalytic amounts of photosensitizers by coupling salt metathesis and reduction to the photopromoted atom abstraction reactions. PMID- 26151155 TI - Lanthanide Nanoparticles: From Design toward Bioimaging and Therapy. PMID- 26151156 TI - Controlled Fabrication of Polypyrrole Surfaces with Overhang Structures by Colloidal Templating. AB - Here we present the fabrication of polypyrrole (PPy) surfaces with a controlled overhang structure. Regularly structured PPy films were produced using interfacial polymerization around a sacrificial crystalline colloidal monolayer at the air/water interface. The morphology of the final inverse colloidal PPy film is controlled by the amount of monomer, the monomer: oxidant ratio and polymerization time. The PPy films exhibit an overhang structure due to depth of particle immersion in the water phase. As a result of the overhang structure, the PPy films are made hydrophobic, although the material itself is hydrophilic. The apparent contact angle of water on the structured surfaces is 109.5 degrees , which is in agreement with the predicted contact angle using the Cassie-Baxter equation for air-filled cavities. This fabrication technique is scalable and can be readily extended to other systems where controlled wettability is required. PMID- 26151157 TI - Linking the Biological and Synthetic Worlds. PMID- 26151158 TI - Quantitative Proteomic Verification of Membrane Proteins as Potential Therapeutic Targets Located in the 11q13 Amplicon in Cancers. AB - Tumor types can be defined cytologically by their regions of chromosomal amplification, which often results in the high expression of both mRNA and proteins of certain genes contained within the amplicon. An important strategy for defining therapeutically relevant targets in these situations is to ascertain which genes are amplified at the protein level and, concomitantly, are key drivers for tumor growth or maintenance. Furthermore, so-called passenger genes that are amplified with driver genes and a manifest on the cell surface can be attractive targets for an antibody-drug conjugate approach (ADC). We employed a tandem mass spectrometry proteomics approach using tumor cell lines to identify the cell surface proteins whose expression correlates with the 11q13 amplicon. The 11q13 amplicon is one of the most frequently amplified chromosomal regions in human cancer, being present in 45% of head and neck and oral squamous cell carcinoma (OSCC) and 13-21% of breast and liver carcinomas. Using a panel of tumor cell lines with defined 11q13 genomic amplification, we identified the membrane proteins that are differentially expressed in an 11q13 amplified cell line panel using membrane-enriched proteomic profiling. We found that DSG3, CD109, and CD14 were differentially overexpressed in head and neck and breast tumor cells with 11q13 amplification. The level of protein expression of each gene was confirmed by Western blot and FACS analysis. Because proteins with high cell surface expression on selected tumor cells could be potential antibody drug conjugate targets, we tested DSG3 and CD109 in antibody piggyback assays and validated that DSG3 and CD109 expression was sufficient to induce antibody internalization and cell killing in 11q13-amplified cell lines. Our results suggest that proteomic profiling using genetically stratified tumors can identify candidate antibody drug conjugate targets. Data are available via ProteomeXchange with the identifier PXD002486. PMID- 26151159 TI - Refraction corrected calibration for aquatic locomotion research: application of Snell's law improves spatial accuracy. AB - Images of underwater objects are distorted by refraction at the water-glass-air interfaces and these distortions can lead to substantial errors when reconstructing the objects' position and shape. So far, aquatic locomotion studies have minimized refraction in their experimental setups and used the direct linear transform algorithm (DLT) to reconstruct position information, which does not model refraction explicitly. Here we present a refraction corrected ray-tracing algorithm (RCRT) that reconstructs position information using Snell's law. We validated this reconstruction by calculating 3D reconstruction error-the difference between actual and reconstructed position of a marker. We found that reconstruction error is small (typically less than 1%). Compared with the DLT algorithm, the RCRT has overall lower reconstruction errors, especially outside the calibration volume, and errors are essentially insensitive to camera position and orientation and the number and position of the calibration points. To demonstrate the effectiveness of the RCRT, we tracked an anatomical marker on a seahorse recorded with four cameras to reconstruct the swimming trajectory for six different camera configurations. The RCRT algorithm is accurate and robust and it allows cameras to be oriented at large angles of incidence and facilitates the development of accurate tracking algorithms to quantify aquatic manoeuvers. PMID- 26151160 TI - PPAR-alpha activation reduced LPS-induced inflammation in alveolar epithelial cells. AB - PURPOSE OF THE STUDY: Acute respiratory distress syndrome (ARDS) represents a major cause of mortality in intensive care patients. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) by fibrates, such as WY-14643 (WY), has been described to beneficially influence inflammation and experimental lung injury. The impact of PPAR-alpha activation on alveolar epithelial cells (AEC) has not been studied yet. MATERIALS AND METHODS: To investigate the effect of PPAR-alpha activator WY in wild-type (WT) and in PPAR-alpha knockout (PPAR alpha(-/-)) animals, mice were treated in different regimes: mice received chow enriched with or without WY for 14 days prior AEC isolation (in-vivo treatment). Furthermore, isolated AEC from both groups were subsequently cultured with or without WY (in-vitro treatment). AEC were stimulated with lipopolysaccharide (LPS). Cell culture supernatant and cell lysate were used for analysis of pro inflammatory mediators. RESULTS: AEC challenged with LPS showed a significantly increased generation of pro-inflammatory mediators. After in-vivo WY-exposure, AEC displayed significantly reduced concentration of TNF-alpha, MIP-2, and TxB2 after LPS stimulation. This beneficial effect was abrogated in PPAR-alpha(-/-) animals. Interestingly, sole in-vitro application of WY-14643 failed to reduce levels of pro-inflammatory mediators whereas we found an additive effect of a combined in-vivo and in-vitro PPAR-alpha activation. PGE2 concentration remained high after LPS challenge and was unaffected by WY treatment. CONCLUSION: PPAR alpha activation by in-vivo exposure to fibrates reduced the inflammatory response in isolated AEC. These findings may facilitate further studies investigating the translation of pharmacological PPAR-alpha activation into clinical therapy of ARDS. PMID- 26151161 TI - Effect of electromagnetic field on cyclic adenosine monophosphate (cAMP) in a human mu-opioid receptor cell model. AB - During the cell communication process, endogenous and exogenous signaling affect normal as well as pathological developmental conditions. Exogenous influences such as extra-low-frequency electromagnetic field (EMF) have been shown to effect pain and inflammation by modulating G-protein receptors, down-regulating cyclooxygenase-2 activity, and affecting the calcium/calmodulin/nitric oxide pathway. Investigators have reported changes in opioid receptors and second messengers, such as cyclic adenosine monophosphate (cAMP), in opiate tolerance and dependence by showing how repeated exposure to morphine decreases adenylate cyclase activity causing cAMP to return to control levels in the tolerant state, and increase above control levels during withdrawal. Resonance responses to biological systems using exogenous EMF signals suggest that frequency response characteristics of the target can determine the EMF biological response. In our past research we found significant down regulation of inflammatory markers tumor necrosis factor alpha (TNF-alpha) and nuclear factor kappa B (NFkappaB) using 5 Hz EMF frequency. In this study cAMP was stimulated in Chinese Hamster Ovary (CHO) cells transfected with human mu-opioid receptors, then exposed to 5 Hz EMF, and outcomes were compared with morphine treatment. Results showed a 23% greater inhibition of cAMP-treating cells with EMF than with morphine. In order to test our results for frequency specific effects, we ran identical experiments using 13 Hz EMF, which produced results similar to controls. This study suggests the use of EMF as a complementary or alternative treatment to morphine that could both reduce pain and enhance patient quality of life without the side-effects of opiates. PMID- 26151162 TI - Novel Spiral-Like Electrode Structure Design for Realization of Two Modes of Energy Harvesting. AB - A planar spiral-like electrodes (PSE) based triboelectric generator has been designed for harvesting rotary mechanical energy to translate into electricity. The performance of the PSE-triboelectric generator with different cycles of spiral-like electrode strip at different rotating speeds is investigated, which demonstrates the open-circuit voltage and short-circuit current of 470 V and 9.0 MUA at rotating speed of 500 r/min with three cycles. In addition, a novel coaxially integrated multilayered PSE-triboelectric generator is built, which can enhance the output of the power effectively. The short-circuit current, the open circuit voltage, and output power reach to 41.55 MUA, 500 V, and 11.73 mW, respectively, at rotating speed of 700 r/min. The output power of the multilayered PSE-triboelectric generator can drive 200 LEDs connected in antiparallel and charge a 110 MUF commercial capacitor to 6 V in 23 s. Besides, due to the spiral-like electrode structure, the PSE-generator can work simultaneously in the modes of triboelectricity and electromagnetic induced electricity by sticking a small magnet on the rotating disk. The electromagnetic induced output power reaches to 21 MUW at a loading resistance of 2 Omega at a rotating rate of 200 r/min. The spiral-like electrode structure not only broadens the electrode structure design but also adds a new function to the electrode. PMID- 26151163 TI - Aerosol particulate matter in the Baltimore metropolitan area: Temporal variation over a six-year period. AB - This study investigates the sources of fine particulate matter (aerodynamic diameter <=2.5 MUm; PM(2.5)) composition for the Baltimore, Maryland, metropolitan area, covering a 6-year period (2008-2013). Data obtained from the U.S. Environmental Protection Agency (EPA) Air Quality System (AQS) were used for the identification of eight chemical speciation clusters (factors), which, as a percentage of the average concentration, were identified as secondary sulfate (31.9%), secondary nitrate (14.3%), gasoline (17.4%), diesel (10.1%), soil (4.0%), biomass burning (11%), marine aerosol (4.1%), and industrial processing (7.2%). The results show predominant influence from vehicle emissions transiting major highways I-695 and I-95 located in the vicinity of the sampling site. Strong influence on PM2.5 mass from biomass burning was found in the first 2 years (2008-2009) due to particulate matter remnants from forest fire events in North Carolina and a strong contribution in 2013 that was due mainly to wood burning during winter. Sulfate, nitrate, soil, and marine aerosol fractions registered very low variability over the 6-year period analyzed. In addition, this study shows a significant reduction in particulate matter from industrial origins after a major industrial source in Baltimore shut down. The results obtained from Baltimore were compared with those from the Beltsville, Maryland, sampling station located 25 miles south of Baltimore for 2011 and 2012, where good agreement was found for most of the factors. IMPLICATIONS: This paper presents the first long-term aerosol speciation analysis in a Mid-Atlantic United States metropolitan area, which is essential for the air quality management agencies in order to revise regulations and reduce human exposure to adverse air quality conditions. The results suggest that although a declining trend in the overall PM2.5 was observed, no significant tendency was observed in the identified sources besides exceptional events such as the impact of wildfires on local air quality and downward contribution from industrial fraction of PM(2.5) after the Steel Mill at Sparrows Point closure in 2012. PMID- 26151164 TI - Self-esteem, Self-focused Attention, and the Mediating Role of Fear of Negative Evaluation in College Students With and Without Asthma. AB - OBJECTIVE: The current study investigated the mediating role of fear of negative evaluation on the relationship between self-focused attention and self-esteem among college students with and without asthma. PARTICIPANTS: Young adults with (n = 148) and without (n = 530) childhood-onset asthma were recruited from a college student population. METHODS: Self-focused attention and fear of negative evaluation measures were completed. Participants also answered questions about inclusion in a social activity. RESULTS: Higher levels of self-focused attention and fear of negative evaluation were associated with lower self-esteem in both groups within the context of social activity participation. Fear of negative evaluation mediated the relationship between self-consciousness and self-esteem. No significant differences were found between groups. CONCLUSIONS: Findings indicate significant relationships among self-focused attention, fear of negative evaluation, and self-esteem in the context of social activity participation. Further examination of self-esteem regarding participation in social activities among college students appears warranted. PMID- 26151165 TI - Bringing the Psychology of Religion and Spirituality Into Community Psychology. PMID- 26151166 TI - Religious Beliefs About Mental Illness Influence Social Support Preferences. AB - Research demonstrates that social support facilitates recovery from a mental illness. Stigma negatively impacts the social support available to persons with mental illness (PWMIs). We investigated how religious beliefs about mental illness influenced the types of social support individuals would be willing to give PWMIs. Christian participants indicated their denominational affiliation and their religious beliefs about mental illness. We then asked participants to imagine a situation in which their friend had depression. Participants indicated their willingness to give secular and spiritual social support (e.g., secular: recommending medication; spiritual: recommending prayer). Christians' beliefs that mental illness results from immorality/sinfulness and that mental illnesses have spiritual causes/treatments both predicted preference for giving spiritual social support. Evangelical Christians endorsed more beliefs that mental illnesses have spiritual causes/treatments than Mainline Protestant and Roman Catholic Christians, and they endorsed more preference for giving spiritual social support than Roman Catholic Christians. PMID- 26151167 TI - Associations Among Religiousness and Community Volunteerism in National Random Samples of American Adults. AB - The connection between religiousness and volunteering for the community can be explained through two distinct features of religion. First, religious organizations are social groups that encourage members to help others through planned opportunities. Second, helping others is regarded as an important value for members in religious organizations to uphold. We examined the relationship between religiousness and self-reported community volunteering in two independent national random surveys of American adults (i.e., the 2005 and 2007 waves of the Baylor Religion Survey). In both waves, frequency of religious service attendance was associated with an increase in likelihood that individuals would volunteer, whether through their religious organization or not, whereas frequency of reading sacred texts outside of religious services was associated with an increase in likelihood of volunteering only for or through their religious organization. The role of religion in community volunteering is discussed in light of these findings. PMID- 26151168 TI - Religious Serpent Handling and Community Relations. AB - Christian serpent handling sects of Appalachia comprise a community that has long been mischaracterized and marginalized by the larger communities surrounding them. To explore this dynamic, this article traces the emergence of serpent handling in Appalachia and the emergence of anti-serpent-handling state laws, which eventually failed to curb the practice, as local communities gave serpent handling groups support. We present two studies to consider for improving community relations with serpent handling sects. In study 1, we present data relating the incidence of reported serpent-bite deaths with the rise of anti serpent-handling laws and their eventual abatement, based on increasing acceptance of serpent handlers by the larger community. Study 2 presents interview data on serpent bites and death that provide explanations for these events from the cultural and religious perspective. We conclude that first-hand knowledge about serpent handlers, and other marginalized groups, helps to lessen suspicion and allows them to be seen as not much different, which are tendencies that are important for promoting inter-community harmony. PMID- 26151169 TI - Links Between Workplace Spirituality, Job-Related Attitudes, and Value Fit in a Non-Profit Agency. AB - We examined perceptions of spirituality and meaning among 192 employees (77% female) from a non-profit organization in a mid-sized Midwestern city in the United States. We hypothesized that employees' values related to workplace spirituality would be positively related to various measures of job satisfaction and general meaning in life. We also examined employees' perceptions of the fit of their co-workers' values with the agency mission and predicted that these perceptions would act as a moderator of the relationship between employees' workplace spirituality and job satisfaction. Our hypotheses were generally supported. Spirituality predicted work contributing to the meaning of life and various facets of job satisfaction. Implications of the importance of employees' perceptions of organizational fit related to spirituality and the perceived fit of co-workers' values with the organizational mission are discussed. PMID- 26151170 TI - Lockdown Legacy: A Qualitative Investigation of Incarceration, Re-Integration, and Faith Communities. AB - Incarceration is often thought to be most relevant to the offender and the victim, yet the network of influence involves parents, children, significant others, and community members. Participants in this project viewed a pre-recorded play highlighting the ripple effects of incarceration, then engaged in a series of discussions sharing their own experiences and concerns. Content analysis of those discussions supported a variety of themes including a perceived lack of productive response from communities of faith. The themes are positioned in the framework of efficacy theory, demonstrating the ebb and flow of this sense of personal control in relation to encounters with incarceration. PMID- 26151171 TI - Stigma as a Barrier to HIV-Related Activities Among African-American Churches in South Carolina. AB - South Carolina has one of the highest HIV/AIDS prevalence rates in the United States. More than 70% of those infected are African American. Traditionally, Black churches have been one of the primary sources of health outreach programs in Southern African-American communities. In this research, we explored the role of HIV-related stigma as a barrier to the acceptance of HIV-related activities in Black churches. A survey of African-American adults in South Carolina found that the overall level of stigma associated with HIV/AIDS was comparable to what has been found in a national probability sample of people in the United States. Consistent with the stigma-as-barrier hypothesis, the degree to which survey respondents endorsed HIV-related stigma was related to less positive attitudes concerning the involvement of Black churches in HIV-related activities. PMID- 26151172 TI - Radiation Effects Investigations Based on Atmospheric Radiation Model (ATMORAD) Considering GEANT4 Simulations of Extensive Air Showers and Solar Modulation Potential. AB - The natural radiative atmospheric environment is composed of secondary cosmic rays produced when primary cosmic rays hit the atmosphere. Understanding atmospheric radiations and their dynamics is essential for evaluating single event effects, so that radiation risks in aviation and the space environment (space weather) can be assessed. In this article, we present an atmospheric radiation model, named ATMORAD (Atmospheric Radiation), which is based on GEANT4 simulations of extensive air showers according to primary spectra that depend only on the solar modulation potential (force-field approximation). Based on neutron spectrometry, solar modulation potential can be deduced using neutron spectrometer measurements and ATMORAD. Some comparisons between our methodology and standard approaches or measurements are also discussed. This work demonstrates the potential for using simulations of extensive air showers and neutron spectroscopy to monitor solar activity. PMID- 26151173 TI - A Case Report: Cytogenetic Dosimetry after Accidental Radiation Exposure during (192)Ir Industrial Radiography Testing. AB - The accidental gamma radiation exposure of an industrial radiography worker and the cytogenetic examination of the worker's blood lymphocytes are described here. The exposure of the worker was due to a malfunction at the entrance into the depleted uranium-shielding device of a (192)Ir source during operation. Because the source was sealed no additional beta radiation exposure was assumed. The worker's thermoluminescent dosimeter indicated an absorbed dose of 0.078 Sv, which presumably took place in December 2013. No clinical symptoms were reported in the case history after the potential exposure to radiation. Four months after the incident it was decided that biological dosimetry using dicentric chromosome and micronucleus analysis would be performed to follow radiation protection aspects and to clarify the radiation dose uncertainties for the exposed worker. Micronucleus frequency was not increased above the laboratory's control value of micronucleus background frequency of unexposed individuals. However, the observed dicentric frequency (0.003 dicentric/cell) differs significantly from the laboratory's background level of dicentric chromosomes in unexposed individuals (0.0007 dicentric/cell). Dicentric analysis in 2,048 metaphase cells resulted in an estimated dose of no more than 0.181 Gy (95% upper confidence level), not less than 0.014 Gy (95% lower confidence level) and a mean dose of 0.066 Gy (photon equivalent whole-body exposure) based on interpolation from the laboratory's calibration curve for (60)Co gamma radiation. Since overdispersion of dicentric chromosomes (u = 9.78) indicated a heterogeneous (partial-body) exposure, we applied the Dolphin method and estimated an exposure of 2.1 Sv affecting 21% of the body volume. Because the overdispersion of dicentric chromosomes was caused by only one heavily damaged cell containing two dicentrics, it is possible that this was an incidental finding. In summary, a radiation overexposure of the radiography worker must be assumed and this case considered as a potential partial-body exposure scenario. PMID- 26151174 TI - Impact of Prolonged Exacerbation Recovery in Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Exacerbations are important and heterogeneous events in the natural history of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To examine the consequences of prolonged exacerbation recovery in patients with COPD. METHODS: A cohort of 384 patients with COPD (FEV1 % predicted 45.8 [SD, 16.6] and a median exacerbation rate of 2.13 per year [interquartile range, 1.0-3.2]) were followed for 1,039 days (interquartile range, 660-1,814) between October 1995 and January 2013. Patients recorded daily worsening of respiratory symptoms and peak expiratory flow (PEF), and when stable underwent spirometry every 3 months, and completed the St. George's Respiratory Questionnaire annually. Exacerbations were diagnosed as 2 consecutive days with one major symptom plus another respiratory symptom. Exacerbation duration was defined as the time from onset to the day preceding 2 consecutive symptom-free days and recovery in PEF as return to preexacerbation levels. MEASUREMENTS AND MAIN RESULTS: A total of 351 patients had one or more exacerbations. Patients with a longer symptom duration (mean, 14.5 d) had a worse St. George's Respiratory Questionnaire total score (0.2 units per 1 day; P = 0.040). A longer symptomatic duration was associated with a shorter interval between exacerbation recovery and onset of the next exacerbation (hazard ratio, 1.004; P = 0.013). For 257 (7.3%) exacerbations, PEF did not recover within 99 days. These exacerbations were associated with symptoms of a viral infection (cold and sore throat). Patients with these nonrecovered exacerbations showed a 10.8 ml/yr (P < 0.001) faster decline in FEV1. CONCLUSIONS: Prolonged exacerbation symptomatic duration is associated with poorer health status and a greater risk of a new event. Exacerbations where lung function does not recover are associated with symptoms of viral infections and accelerated decline in FEV1. PMID- 26151175 TI - Intracellular glutathione production, but not protein glycation, underlies the protective effects of captopril against 2-deoxy-D-ribose-induced beta-cell damage. AB - Our previous study reported that both oxidative stress and protein glycation were the principal mechanisms underlying 2-deoxy-D-ribose (dRib)-induced pancreatic beta-cell damage. The aim of the present study was to investigate the effects of captopril on dRib-induced damage in pancreatic beta-cells, as well as to determine the mechanisms underlying these effects. Treatment with dRib increased the levels of cytotoxicity, apoptosis, and intracellular reactive oxygen species in Syrian hamster insulinoma HIT-T15 cells; however, pretreatment with captopril significantly inhibited the effects of dRib. The intracellular levels of reduced and oxidized glutathione were depleted following treatment with dRib; however, these levels were restored following HIT-T15 cell treatment with captopril. In rat islets, dRib stimulation suppressed the mRNA expression levels of insulin, and pancreatic and duodenal homeobox 1, as well as insulin content; however, these effects were dose-dependently reversed by treatment with captopril. Treatment with buthionine sulfoximine, an inhibitor of intracellular glutathione biosynthesis, inhibited the protective effects of captopril on dRib-mediated glutathione depletion and cytotoxicity in HIT-T15 cells. Following incubation with albumin, dRib increased the formation of dicarbonyl and advanced glycation end products. Treatment with captopril did not inhibit the dRib-induced increase in production of dicarbonyl and advanced glycation end products. In conclusion, treatment with captopril reversed dRib-induced oxidative damage and suppression of insulin expression in beta-cells. The mechanism underlying the protective effects of captopril may involve increased intracellular glutathione production, rather than protein glycation. PMID- 26151176 TI - A Novel Dietary Assessment Method to Measure a Healthy and Sustainable Diet Using the Mobile Food Record: Protocol and Methodology. AB - The world-wide rise in obesity parallels growing concerns of global warming and depleting natural resources. These issues are often considered separately but there may be considerable benefit to raising awareness of the impact of dietary behaviours and practices on the food supply. Australians have diets inconsistent with recommendations, typically low in fruit and vegetables and high in energy dense nutrient-poor foods and beverages (EDNP). These EDNP foods are often highly processed and packaged, negatively influencing both health and the environment. This paper describes a proposed dietary assessment method to measure healthy and sustainable dietary behaviours using 4-days of food and beverage images from the mobile food record (mFR) application. The mFR images will be assessed for serves of fruit and vegetables (including seasonality), dairy, eggs and red meat, poultry and fish, ultra-processed EDNP foods, individually packaged foods, and plate waste. A prediction model for a Healthy and Sustainable Diet Index will be developed and tested for validity and reliability. The use of the mFR to assess adherence to a healthy and sustainable diet is a novel and innovative approach to dietary assessment and will have application in population monitoring, guiding intervention development, educating consumers, health professionals and policy makers, and influencing dietary recommendations. PMID- 26151177 TI - The Cross-Sectional Association of Energy Intake and Dietary Energy Density with Body Composition of Children in Southwest China. AB - OBJECTIVE: We examined whether dietary energy intake (EI) and dietary energy density (ED) were cross-sectionally associated with body composition of children living in Southwest China. DESIGN AND METHODS: Multivariate regression analyses were performed on three day, 24 h dietary recall data and information on potential confounders from 1207 participants aged 8-14 years. EI was calculated from all foods and drinks and ED was classified into five categories. Body mass index (BMI) z-scores, percentage of body fat (%BF), fat mass index (FMI), fat free mass index (FFMI) and ratio of waist to hip circumference (WHR) were used to describe body composition. RESULTS: Boys with higher total EI had higher BMI z scores, %BF, and FMI than boys with lower total EI both before and after measurements were adjusted for confounders (age, fiber intake, physical activity, the timing of adding complementary foods, paternal education level and maternal BMI) (p <= 0.04). However, EI was not associated with body composition in girls. Dietary ED, in any category, was not associated with body composition in either gender. CONCLUSIONS: Dietary ED was not associated with body composition of children in Southwest China, while dietary EI in boys, not girls, was positively associated with body composition. Reducing dietary energy intake may help to prevent obesity and related diseases in later life among boys living in Southwest China. PMID- 26151178 TI - A Randomized, Double-Blind, Parallel Study to Evaluate the Dose-Response of Three Different Vitamin D Treatment Schemes on the 25-Hydroxyvitamin D Serum Concentration in Patients with Vitamin D Deficiency. AB - Many people worldwide are vitamin D (VTD) deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OH)D concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OH)D. One hundred and fifty (150) subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8. Whereas 25(OH)D baseline values were not different between groups (p = 0.42), a significant increase was observed at Week 12 (p < 0.0001) with a mean change from baseline of 7.72 +/- 5.08, 13.3 +/- 5.88 and 20.12 +/- 7.79 ng/mL. A plateau was reached after eight weeks. No related adverse event was recorded. This study demonstrated a linear dose-response relationship with an increase in 25(OH)D levels proportional to the dose administered. In conclusion, a loading dose of 200,000 IU VTD3 followed by a monthly dose of 100,000 IU is the best dosing schedule to quickly and safely correct the VTD status. PMID- 26151179 TI - Aquaporin 1 promotes the proliferation and migration of lung cancer cell in vitro. AB - To examine the potential role of aquaporin 1 (AQP1) in lung cancer progression, the effects of AQP1 expression and underlying mechanisms on cell proliferation and migration were investigated on LLC and LTEP-A2 cell lines in vitro. LLC and LTEP-A2 lung cancer cells with a discrepant AQP1 expression level were used to determine the role of AQP1 in cancer cell proliferation and migration potential. An immuno-fluorescence assay was used to detect AQP1 expression levels in the LLC and LTEP-A2 cell lines. The method targeting the knockdown of AQP1 on lung cancer cell lines by siRNA was established and validated by RT-PCR and western blot analysis. The proliferation and migration abilities of AQP1 knockdown cell lines were detected by MTT, invasion and wound-healing assays. Moreover, the alteration of MMP-2, MMP-9, TGF-beta and epidermal growth factor receptor (EGFR) expression, associated with the migration and metastasis potential of lung cancer cell lines, was identified by western blot analysis in transfected cells. In the tumor cell migration and invasion test, AQP1 knockdown significantly decreased the migration and invasion of AQP1-siRNA cells. Additionally, the expression levels of MMPs were markedly decreased after AQP1-siRNA treatment in the two cell lines. Moreover, the decrease of MMP-2/-9 expression on lung cancer cell lines was associated with AQP1-siRNA doses. However, AQP1 knockdown did not have a significant effect on TGF-beta and EGFR. The results suggest that AQP1 may facilitate lung cancer cell proliferation and migration in an MMP-2 and-9 dependent manner. PMID- 26151181 TI - Clarification of check-up recommendations in adults. PMID- 26151180 TI - Immunohistochemical analysis of phosphorylated mammalian target of rapamycin and its downstream signaling components in invasive breast cancer. AB - The present study aimed to investigate whether the mammalian target of rapamycin (mTOR) signaling pathway is activated in invasive breast cancer. The expression levels of phosphorylated (p)-mTOR at ser2448 were detected, as well as the expression levels of its downstream signaling molecules: Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and p70 ribosomal protein S6 kinase 1 (S6K1). The correlation between p-mTOR, p-4E-BP1, p-S6K1, and the clinicopathological parameters of breast cancer were also determined. p-mTOR, p 4E-BP1 and p-S6K1 expression was detected in 285 breast cancer tumor samples and adjacent normal tissue samples using immunohistochemistry. The expression levels and the location of the proteins were analyzed and compared in the various tissue samples. Multivariate Cox regression was used to analyze the clinicopathological factors and prognosis associated with the tissue samples. The disease-free survival rate was examined using survival analyses and Log-rank tests. The results of the present study indicated that the expression levels of p-mTOR, p-4E BP1, and p-S6K1 were significantly higher in breast cancer tissue, as compared with normal tissue (P<0.01). p-mTOR was predominantly expressed in the cytoplasm, whereas p-4E-BP1 and p-S6K1 were predominantly co-expressed in the cytoplasm and the nucleus. In addition, p-4E-BP1 and p-S6K1 were more likely to be expressed in the cytoplasm in breast cancer tissue samples, as compared with normal tissue samples (P<0.001). Positive p-mTOR was not significantly correlated with positive p-4E-BP1 and p-S6K1 expression. The survival analyses of the patients with positive p-mTOR, p-4E-BP1, and p-S6K1 tissue samples were not significantly different from those of the patients with negative tissue samples (P>0.05). Thus suggesting that these markers are not adequate risk factors for disease free survival (P>0.05). In conclusion, the results of the present study suggested that p-mTOR, p-4E-BP1, and p-S6K1 are activated in invasive breast cancer. In addition, the exclusive expression of p-4E-BP1 and p-S6K1 in the cytoplasm may be characteristic of progressive breast cancer. However, p-mTOR, p-4E-BP1, and p S6K1 are not prognostic factors for breast cancer. PMID- 26151182 TI - Editorial. PMID- 26151183 TI - Measured Gene-Environment Interactions in Psychopathology: Concepts, Research Strategies, and Implications for Research, Intervention, and Public Understanding of Genetics. AB - There is much curiosity about interactions between genes and environmental risk factors for psychopathology, but this interest is accompanied by uncertainty. This article aims to address this uncertainty. First, we explain what is and is not meant by gene-environment interaction. Second, we discuss reasons why such interactions were thought to be rare in psychopathology, and argue instead that they ought to be common. Third, we summarize emerging evidence about gene environment interactions in mental disorders. Fourth, we argue that research on gene-environment interactions should be hypothesis driven, and we put forward strategies to guide future studies. Fifth, we describe potential benefits of studying measured gene-environment interactions for basic neuroscience, gene hunting, intervention, and public understanding of genetics. We suggest that information about nurture might be harnessed to make new discoveries about the nature of psychopathology. PMID- 26151184 TI - Are Emotions Natural Kinds? AB - Laypeople and scientists alike believe that they know anger, or sadness, or fear, when they see it. These emotions and a few others are presumed to have specific causal mechanisms in the brain and properties that are observable (on the face, in the voice, in the body, or in experience)-that is, they are assumed to be natural kinds. If a given emotion is a natural kind and can be identified objectively, then it is possible to make discoveries about that emotion. Indeed, the scientific study of emotion is founded on this assumption. In this article, I review the accumulating empirical evidence that is inconsistent with the view that there are kinds of emotion with boundaries that are carved in nature. I then consider what moving beyond a natural-kind view might mean for the scientific understanding of emotion. PMID- 26151185 TI - Do Cognitive Changes Accompany Developments in the Adolescent Brain? AB - The news that the brain continues to develop through much of adolescence risks becoming an explanation for anything and everything about teenagers and suggests the need for closer analysis. Central to such analysis is clarifying what develops at a psychological level during these years. An examination of contemporary research data on adolescent cognitive development identifies increased executive control as a major dimension of cognitive development during the second decade of life. Such development is consistent with changes occurring in the brain during this period. PMID- 26151187 TI - Leon Festinger: Lunch With Leon. PMID- 26151186 TI - Mental Exercise and Mental Aging: Evaluating the Validity of the "Use It or Lose It" Hypothesis. AB - It is widely believed that keeping mentally active will prevent age-related mental decline. The primary prediction of this mental-exercise hypothesis is that the rate of age-related decline in measures of cognitive functioning will be less pronounced for people who are more mentally active, or, equivalently, that the cognitive differences among people who vary in level of mental activity will be greater with increased age. Although many training studies, and comparisons involving experts, people in specific occupations, and people whose mental activity levels are determined by their self-reports, have found a positive relation between level of activity and level of cognitive functioning, very few studies have found an interactive effect of age and mental activity on measures of cognitive functioning. Despite the current lack of empirical evidence for the idea that the rate of mental aging is moderated by amount of mental activity, there may be personal benefits to assuming that the mental-exercise hypothesis is true. PMID- 26151188 TI - Instructions to Contributors. PMID- 26151189 TI - Structure-Based Design of Macrocyclic Coagulation Factor VIIa Inhibitors. AB - On the basis of a crystal structure of a phenylpyrrolidine lead and subsequent molecular modeling results, we designed and synthesized a novel series of macrocyclic FVIIa inhibitors. The optimal 16-membered macrocycle was 60-fold more potent than an acyclic analog. Further potency optimization by incorporation of P1' alkyl sulfone and P2 methyl groups provided a macrocycle with TF/FVIIa Ki = 1.6 nM, excellent selectivity against a panel of seven serine proteases, and FVII deficient prothrombin time EC2x = 1.2 MUM. Discovery of this potent, selective macrocyclic scaffold opens new possibilities for the development of orally bioavailable FVIIa inhibitors. PMID- 26151190 TI - Cell response to viral infection: search for new therapeutric targets. PMID- 26151191 TI - Validation of a multi-analyte HPLC-DAD method for determination of uric acid, creatinine, homovanillic acid, niacinamide, hippuric acid, indole-3-acetic acid and 2-methylhippuric acid in human urine. AB - During the last decades exposure sciences and epidemiological studies attracts more attention to unravel the mechanisms for the development of chronic diseases. According to this an existing HPLC-DAD method for determination of creatinine in urine samples was expended for seven analytes and validated. Creatinine, uric acid, homovanillic acid, niacinamide, hippuric acid, indole-3-acetic acid, and 2 methylhippuric acid were separated by gradient elution (formate buffer/methanol) using an Eclipse Plus C18 Rapid Resolution column (4.6mm*100mm). No interfering signals were detected in mobile phase. After injection of blank urine samples signals for the endogenous compounds but no interferences were detected. All analytes were linear in the selected calibration range and a non weighted calibration model was chosen. Bias, intra-day and inter-day precision for all analytes were below 20% for quality control (QC) low and below 10% for QC medium and high. The limits of quantification in mobile phase were in line with reported reference values but had to be adjusted in urine for homovanillic acid (45mg/L), niacinamide 58.5(mg/L), and indole-3-acetic acid (63mg/L). Comparison of creatinine data obtained by the existing method with those of the developed method showing differences from -120mg/L to +110mg/L with a mean of differences of 29.0mg/L for 50 authentic urine samples. Analyzing 50 authentic urine samples, uric acid, creatinine, hippuric acid, and 2-methylhippuric acid were detected in (nearly) all samples. However, homovanillic acid was detected in 40%, niacinamide in 4% and indole-3-acetic acid was never detected within the selected samples. PMID- 26151192 TI - Fast filtration sampling protocol for mammalian suspension cells tailored for phosphometabolome profiling by capillary ion chromatography - tandem mass spectrometry. AB - Capillary ion chromatography (capIC) is the premium separation technology for low molecular phosphometabolites and nucleotides in biological extracts. Removal of excessive amounts of salt during sample preparation stages is a prerequisite to enable high quality capIC separation in combination with reproducible and sensitive MS detection. Existing sampling protocols for mammalian cells used for GC-MS and LC-MS metabolic profiling can therefore not be directly applied to capIC separations. Here, the development of a fast filtration sampling protocol for mammalian suspension cells tailored for quantitative profiling of the phosphometabolome on capIC-MS/MS is presented. The whole procedure from sampling the culture to transfer of filter to quenching and extraction solution takes less than 10s. To prevent leakage it is critical that a low vacuum pressure is applied, and satisfactorily reproducibility was only obtained by usage of a vacuum pressure controlling device. A vacuum of 60mbar was optimal for filtration of multiple myeloma Jjn-3 cell cultures through 5MUm polyvinylidene (PVDF) filters. A quick deionized water (DI-water) rinse step prior to extraction was tested, and significantly higher metabolite yields were obtained during capIC MS/MS analyses in this extract compared to extracts prepared by saline and reduced saline (25%) washing steps only. In addition, chromatographic performance was dramatically improved. Thus, it was verified that a quick DI-water rinse is tolerated by the cells and can be included as the final stage during filtration. Over 30 metabolites were quantitated in JJN-3 cell extracts by using the optimized sampling protocol with subsequent capIC-MS/MS analysis, and up to 2 million cells can be used in a single filtration step for the chosen filter and vacuum pressure. The technical set-up is also highly advantageous for microbial metabolome filtration protocols after optimization of vacuum pressure and washing solutions, and the reduced salt content of the extract will also improve the quality of LC-MS analysis due to lower salt adduct ion formation. PMID- 26151193 TI - Stereoselective Total Syntheses of Guanacastepenes N and O. AB - Total syntheses of (+/-)-guanacastepenes N and O were accomplished with 2 cycloheptenone as starting material. The six- and five-membered rings of the core [5, 7, 6] ring skeleton were constructed with an intramolecular Diels-Alder reaction and alpha-carbonyl radical cyclization. The quaternary centers and their stereochemistry were established with sequential Cu(I)-mediated conjugate additions. A sequence with dihydroxylation, conjugate addition, and beta elimination was devised to incorporate all oxygen functionalities at positions. The total synthesis is adaptable for the synthesis of enantiopure guanacastepenes N and O using chiral intermediate (R)-3-vinyl-2-cycloheptenol obtained from lipase-catalyzed kinetic resolution. PMID- 26151194 TI - The effects of methylmercury exposure on behavior and biomarkers of oxidative stress in adult mice. AB - Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies (in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5 mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3. PMID- 26151195 TI - Ultrahigh Aspect Ratio Copper-Nanowire-Based Hybrid Transparent Conductive Electrodes with PEDOT:PSS and Reduced Graphene Oxide Exhibiting Reduced Surface Roughness and Improved Stability. AB - Copper nanowires (CuNWs) with ultrahigh aspect ratio are synthesized with a solution process and spray-coated onto select substrates to fabricate transparent conductive electrodes (TCEs). Different annealing methods are investigated and compared for effectiveness and convenience. The CuNWs are subsequently combined with the conductive polymer poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) ( PEDOT: PSS) or with reduced graphene oxide (rGO) platelets in order to reduce the surface roughness and improve the durability of the fabricated TCEs. Our best-performing PEDOT: PSS/CuNW films have optical transmittance T550 = 84.2% (at lambda = 550 nm) and sheet resistance Rs = 25 Omega/sq, while our best CuNW/rGO films have T550 = 84% and Rs = 21.7 Omega/sq. PMID- 26151197 TI - Correction to "A Mononuclear Manganese(II) Complex Demonstrates a Strategy To Simultaneously Image and Treat Oxidative Stress". PMID- 26151196 TI - Histone deacetylase inhibitor restores surfactant protein-C expression in alveolar-epithelial type II cells and attenuates bleomycin-induced pulmonary fibrosis in vivo. AB - AIM: Surfactant protein-C (SP-C) of alveolar epithelial type II cells (ATII) plays a key role in maintaining alveolar integrity and repair. Mutations or decreased expression of SFTPC, the gene encoding SP-C, causes ATII injury and aberrant repair of the lung tissue to develop pulmonary fibrosis. Histone deacetylases (HDACs) epigenetically remove acetyl groups from acetylated histones and regulate transcription. HDAC inhibitors attenuated epithelial-to-mesenchymal transition (EMT) and fibrotic disorders. The aim of this study is to investigate whether Trichostatin A (TSA), a pan-HDAC inhibitor, epigenetically exerts a protective effect on ATII against fibrotic changes via the restoration of SFTPC expression. MATERIALS AND METHODS: We treated A549 cells with TGF-beta1 to induce EMT, followed by TSA treatment. We evaluated SFTPC mRNA, histone acetylation levels in the SFTPC gene promoter region, and pro-SP-C protein. C57BL6/J mice were treated with intratracheal bleomycin instillation followed by TSA administration. Histological changes and Sftpc mRNA expression in isolated ATII were evaluated. RESULTS: TGF-beta1 treatment decreased SFTPC mRNA in A549 cells. TSA restored SFTPC mRNA, and increased histone H4 acetylation in the SFTPC promoter region in vitro. The administration of TSA partially attenuated BLM induced pulmonary fibrosis and increased the Sftpc mRNA expression in isolated ATII from bleomycin-treated lungs in vivo. CONCLUSIONS: Decreased expression of SFTPC by TGF-beta1 treatment was restored by TSA via hyperacetylation of histone H4 in the promoter region. TSA partially attenuated pulmonary fibrosis and increased Sftpc mRNA in ATII. Our findings suggest that the epigenetic restoration of SP-C would be a therapeutic target for pulmonary fibrosis. PMID- 26151198 TI - Applying behavioral theories to invasive animal management: Towards an integrated framework. AB - Invasive species wreak an estimated $1.4 trillion in damages globally, each year. To have any hope of reducing this damage, best-practice control strategies must incorporate behavior change interventions. Traditional interventions, based on the knowledge-transfer model, assume that if land managers are properly educated about risks and strategies, they will develop supportive attitudes and implement appropriate control strategies. However, the social sciences have produced a large number of behavioral models and frameworks that demonstrate that knowledge transfer, by itself, fails to change behavior. The challenge then lies in knowing which behavioral model to choose, and when, from a potentially overwhelming 'universe'. In this paper, we review nine behavior theories relevant to invasive species management. We then introduce the Behavior Change Wheel as a tool for integrating these theories into a single practical framework. This framework links drivers of and barriers to behavior change with intervention strategies and policies, in what we consider, from an applied perspective, to be an important advance. PMID- 26151199 TI - Identification of genes associated with osteoarthritis by microarray analysis. AB - The aim of the present study was to investigate the mechanisms of osteoarthritis (OA). Raw microarray data (GSE51588) were downloaded from Gene Expression Omnibus, including samples from OA (n=20) and non-OA (n=5) knee lateral and medial tibial plateaus. Differentially expressed genes (DEGs) were identified using Student's t-test. Functional and pathway enrichment analyses were performed for the upregulated and downregulated DEGs. A protein-protein interaction network (PPI) was constructed according to the Search Tool for the Retrieval of Interacting Genes/Proteins database, and module analysis of the PPI network was performed using CFinder. The protein domain enrichment analysis for genes in modules was performed using the INTERPRO database. A total of 869 upregulated and 508 downregulated DEGs were identified. The enriched pathways of downregulated and upregulated DEGs were predominantly associated with the cell cycle (BUB1, BUB1B, CCNA2, CCNB1 and CCNE1), and extracellular matrix (ECM)-receptor interaction (CD36, COL11A2, COL1A1, COL2A1 and COL3A1). Functional enrichment analysis of the DEGs demonstrated that FGF19, KIF11 and KIF2C were involved in the response to stress and that ACAN, ADAMTS10 and BGN were associated with proteinaceous ECM. The top protein domain was IPR001752: Kinesin motor region involving three genes (KIF2C, KIF11 and KIF20A). The identified DEGs, including KIF2C, KIF11 and KIF20A, may be significant in the pathogenesis of OA. PMID- 26151200 TI - Prevalence of Staphylococcus aureus and methicillin resistant Staphylococcus aureus (MRSA) in the oral cavity. AB - OBJECTIVE: To assess the prevalence of Staphylococcus aureus and methicillin resistant Staphylococcus aureus (MRSA) in plaque and tongue samples from systemically healthy subjects with periodontal health, gingivitis or chronic periodontitis. METHODS: After screening 720 potentially eligible subjects, 154 systemically healthy participants were ultimately enrolled in the current study. Subgingival samples were taken from the first molars and the tongue and analyzed for the presence of S. aureus and MRSA by polymerase chain reaction (PCR), using primers and conditions previously described in the literature. In addition, samples were taken from deep periodontal pockets of chronic periodontitis patients. Statistical analysis was performed by applying non-parametric tests (Kruskal-Wallis for clinical parameters, and z-test with Bonferroni corrections for distributions of assessed parameters). All comparisons were set at the 0.05 significance level. RESULTS: S. aureus was detected in 18% of all participants and in 10% of the samples tested. No significant differences were found in its distribution among the three investigated groups (z-test for proportions with Bonferroni corrections, p>0.05). The mecA gene was not present in any of the S. aureus found. CONCLUSIONS: S. aureus can be found in the oral environment regardless of the periodontal conditions and therefore should be considered as a member of the transient flora not participating in periodontal pathology. Subgingival sites and tongue surfaces seem to be an unusual habitat of MRSA. PMID- 26151201 TI - Biomedical informatics in Switzerland: need for action. AB - Biomedical informatics (BMI) is an umbrella scientific field that covers many domains, as defined several years ago by the International Medical Informatics Association and the American Medical Informatics Association, two leading players in the field. For example, one of the domains of BMI is clinical informatics, which has been formally recognised as a medical subspecialty by the American Board of Medical Specialty since 2011. Most OECD (Organisation for Economic Co operation and Development) countries offer very strong curricula in the field of BMI, strong research and development funding with clear tracks and, for most of them, inclusion of BMI in the curricula of health professionals, but BMI remains only marginally recognised in Switzerland. Recent major changes, however, such as the future federal law on electronic patient records, the personalised health initiative or the growing empowerment of citizens towards their health data, are adding much weight to the need for BMI capacity-building in Switzerland. PMID- 26151202 TI - Augmented Robotics Dialog System for Enhancing Human-Robot Interaction. AB - Augmented reality, augmented television and second screen are cutting edge technologies that provide end users extra and enhanced information related to certain events in real time. This enriched information helps users better understand such events, at the same time providing a more satisfactory experience. In the present paper, we apply this main idea to human-robot interaction (HRI), to how users and robots interchange information. The ultimate goal of this paper is to improve the quality of HRI, developing a new dialog manager system that incorporates enriched information from the semantic web. This work presents the augmented robotic dialog system (ARDS), which uses natural language understanding mechanisms to provide two features: (i) a non-grammar multimodal input (verbal and/or written) text; and (ii) a contextualization of the information conveyed in the interaction. This contextualization is achieved by information enrichment techniques that link the extracted information from the dialog with extra information about the world available in semantic knowledge bases. This enriched or contextualized information (information enrichment, semantic enhancement or contextualized information are used interchangeably in the rest of this paper) offers many possibilities in terms of HRI. For instance, it can enhance the robot's pro-activeness during a human-robot dialog (the enriched information can be used to propose new topics during the dialog, while ensuring a coherent interaction). Another possibility is to display additional multimedia content related to the enriched information on a visual device. This paper describes the ARDS and shows a proof of concept of its applications. PMID- 26151203 TI - Graph Structure-Based Simultaneous Localization and Mapping Using a Hybrid Method of 2D Laser Scan and Monocular Camera Image in Environments with Laser Scan Ambiguity. AB - Localization is an essential issue for robot navigation, allowing the robot to perform tasks autonomously. However, in environments with laser scan ambiguity, such as long corridors, the conventional SLAM (simultaneous localization and mapping) algorithms exploiting a laser scanner may not estimate the robot pose robustly. To resolve this problem, we propose a novel localization approach based on a hybrid method incorporating a 2D laser scanner and a monocular camera in the framework of a graph structure-based SLAM. 3D coordinates of image feature points are acquired through the hybrid method, with the assumption that the wall is normal to the ground and vertically flat. However, this assumption can be relieved, because the subsequent feature matching process rejects the outliers on an inclined or non-flat wall. Through graph optimization with constraints generated by the hybrid method, the final robot pose is estimated. To verify the effectiveness of the proposed method, real experiments were conducted in an indoor environment with a long corridor. The experimental results were compared with those of the conventional GMappingapproach. The results demonstrate that it is possible to localize the robot in environments with laser scan ambiguity in real time, and the performance of the proposed method is superior to that of the conventional approach. PMID- 26151204 TI - Energy Harvesting from Upper-Limb Pulling Motions for Miniaturized Human-Powered Generators. AB - The human-powered self-generator provides the best solution for individuals who need an instantaneous power supply for travel, outdoor, and emergency use, since it is less dependent on weather conditions and occupies less space than other renewable power supplies. However, many commercial portable self-generators that employ hand-cranking are not used as much as expected in daily lives although they have enough output capacity due to their intensive workload. This study proposes a portable human-powered generator which is designed to obtain mechanical energy from an upper limb pulling motion for improved human motion economy as well as efficient human-mechanical power transfer. A coreless axial flux permanent magnet machine (APMM) and a flywheel magnet rotor were used in conjunction with a one-way clutched power transmission system in order to obtain effective power from the pulling motion. The developed prototype showed an average energy conversion efficiency of 30.98% and an average output power of 0.32 W with a maximum of 1.89 W. Its small form factor (50 mm * 32 mm * 43.5 mm, 0.05 kg) and the substantial electricity produced verify the effectiveness of the proposed method in the utilization of human power. It is expected that the developed generator could provide a mobile power supply. PMID- 26151205 TI - Foot Pose Estimation Using an Inertial Sensor Unit and Two Distance Sensors. AB - There are many inertial sensor-based foot pose estimation algorithms. In this paper, we present a methodology to improve the accuracy of foot pose estimation using two low-cost distance sensors (VL6180) in addition to an inertial sensor unit. The distance sensor is a time-of-flight range finder and can measure distance up to 20 cm. A Kalman filter with 21 states is proposed to estimate both the calibration parameter (relative pose of distance sensors with respect to the inertial sensor unit) and foot pose. Once the calibration parameter is obtained, a Kalman filter with nine states can be used to estimate foot pose. Through four activities (walking, dancing step, ball kicking, jumping), it is shown that the proposed algorithm significantly improves the vertical position estimation. PMID- 26151206 TI - An Electromagnetic Sensor with a Metamaterial Lens for Nondestructive Evaluation of Composite Materials. AB - This paper proposes the study and implementation of a sensor with a metamaterial (MM) lens in electromagnetic nondestructive evaluation (eNDE). Thus, the use of a new type of MM, named Conical Swiss Rolls (CSR) has been proposed. These structures can serve as electromagnetic flux concentrators in the radiofrequency range. As a direct application, plates of composite materials with carbon fibers woven as reinforcement and polyphenylene sulphide as matrix with delaminations due to low energy impacts were examined. The evaluation method is based on the appearance of evanescent modes in the space between carbon fibers when the sample is excited with a transversal magnetic along z axis (TMz) polarized electromagnetic field. The MM lens allows the transmission and intensification of evanescent waves. The characteristics of carbon fibers woven structure became visible and delaminations are clearly emphasized. The flaws can be localized with spatial resolution better than lambda/2000. PMID- 26151208 TI - Secure Data Aggregation with Fully Homomorphic Encryption in Large-Scale Wireless Sensor Networks. AB - With the rapid development of wireless communication technology, sensor technology, information acquisition and processing technology, sensor networks will finally have a deep influence on all aspects of people's lives. The battery resources of sensor nodes should be managed efficiently in order to prolong network lifetime in large-scale wireless sensor networks (LWSNs). Data aggregation represents an important method to remove redundancy as well as unnecessary data transmission and hence cut down the energy used in communication. As sensor nodes are deployed in hostile environments, the security of the sensitive information such as confidentiality and integrity should be considered. This paper proposes Fully homomorphic Encryption based Secure data Aggregation (FESA) in LWSNs which can protect end-to-end data confidentiality and support arbitrary aggregation operations over encrypted data. In addition, by utilizing message authentication codes (MACs), this scheme can also verify data integrity during data aggregation and forwarding processes so that false data can be detected as early as possible. Although the FHE increase the computation overhead due to its large public key size, simulation results show that it is implementable in LWSNs and performs well. Compared with other protocols, the transmitted data and network overhead are reduced in our scheme. PMID- 26151207 TI - H2RM: A Hybrid Rough Set Reasoning Model for Prediction and Management of Diabetes Mellitus. AB - Diabetes is a chronic disease characterized by high blood glucose level that results either from a deficiency of insulin produced by the body, or the body's resistance to the effects of insulin. Accurate and precise reasoning and prediction models greatly help physicians to improve diagnosis, prognosis and treatment procedures of different diseases. Though numerous models have been proposed to solve issues of diagnosis and management of diabetes, they have the following drawbacks: (1) restricted one type of diabetes; (2) lack understandability and explanatory power of the techniques and decision; (3) limited either to prediction purpose or management over the structured contents; and (4) lack competence for dimensionality and vagueness of patient's data. To overcome these issues, this paper proposes a novel hybrid rough set reasoning model (H2RM) that resolves problems of inaccurate prediction and management of type-1 diabetes mellitus (T1DM) and type-2 diabetes mellitus (T2DM). For verification of the proposed model, experimental data from fifty patients, acquired from a local hospital in semi-structured format, is used. First, the data is transformed into structured format and then used for mining prediction rules. Rough set theory (RST) based techniques and algorithms are used to mine the prediction rules. During the online execution phase of the model, these rules are used to predict T1DM and T2DM for new patients. Furthermore, the proposed model assists physicians to manage diabetes using knowledge extracted from online diabetes guidelines. Correlation-based trend analysis techniques are used to manage diabetic observations. Experimental results demonstrate that the proposed model outperforms the existing methods with 95.9% average and balanced accuracies. PMID- 26151209 TI - Smart City Mobility Application--Gradient Boosting Trees for Mobility Prediction and Analysis Based on Crowdsourced Data. AB - Mobility management represents one of the most important parts of the smart city concept. The way we travel, at what time of the day, for what purposes and with what transportation modes, have a pertinent impact on the overall quality of life in cities. To manage this process, detailed and comprehensive information on individuals' behaviour is needed as well as effective feedback/communication channels. In this article, we explore the applicability of crowdsourced data for this purpose. We apply a gradient boosting trees algorithm to model individuals' mobility decision making processes (particularly concerning what transportation mode they are likely to use). To accomplish this we rely on data collected from three sources: a dedicated smartphone application, a geographic information systems-based web interface and weather forecast data collected over a period of six months. The applicability of the developed model is seen as a potential platform for personalized mobility management in smart cities and a communication tool between the city (to steer the users towards more sustainable behaviour by additionally weighting preferred suggestions) and users (who can give feedback on the acceptability of the provided suggestions, by accepting or rejecting them, providing an additional input to the learning process). PMID- 26151210 TI - Evolution of RFID Applications in Construction: A Literature Review. AB - Radio frequency identification (RFID) technology has been widely used in the field of construction during the last two decades. Basically, RFID facilitates the control on a wide variety of processes in different stages of the lifecycle of a building, from its conception to its inhabitance. The main objective of this paper is to present a review of RFID applications in the construction industry, pointing out the existing developments, limitations and gaps. The paper presents the establishment of the RFID technology in four main stages of the lifecycle of a facility: planning and design, construction and commission and operation and maintenance. Concerning this last stage, an RFID application aiming to facilitate the identification of pieces of furniture in scanned inhabited environments is presented. Conclusions and future advances are presented at the end of the paper. PMID- 26151211 TI - Using Open Geographic Data to Generate Natural Language Descriptions for Hydrological Sensor Networks. AB - Providing descriptions of isolated sensors and sensor networks in natural language, understandable by the general public, is useful to help users find relevant sensors and analyze sensor data. In this paper, we discuss the feasibility of using geographic knowledge from public databases available on the Web (such as OpenStreetMap, Geonames, or DBpedia) to automatically construct such descriptions. We present a general method that uses such information to generate sensor descriptions in natural language. The results of the evaluation of our method in a hydrologic national sensor network showed that this approach is feasible and capable of generating adequate sensor descriptions with a lower development effort compared to other approaches. In the paper we also analyze certain problems that we found in public databases (e.g., heterogeneity, non standard use of labels, or rigid search methods) and their impact in the generation of sensor descriptions. PMID- 26151212 TI - Optimal Sensor Selection for Classifying a Set of Ginsengs Using Metal-Oxide Sensors. AB - The sensor selection problem was investigated for the application of classification of a set of ginsengs using a metal-oxide sensor-based homemade electronic nose with linear discriminant analysis. Samples (315) were measured for nine kinds of ginsengs using 12 sensors. We investigated the classification performances of combinations of 12 sensors for the overall discrimination of combinations of nine ginsengs. The minimum numbers of sensors for discriminating each sample set to obtain an optimal classification performance were defined. The relation of the minimum numbers of sensors with number of samples in the sample set was revealed. The results showed that as the number of samples increased, the average minimum number of sensors increased, while the increment decreased gradually and the average optimal classification rate decreased gradually. Moreover, a new approach of sensor selection was proposed to estimate and compare the effective information capacity of each sensor. PMID- 26151213 TI - Traffic Behavior Recognition Using the Pachinko Allocation Model. AB - CCTV-based behavior recognition systems have gained considerable attention in recent years in the transportation surveillance domain for identifying unusual patterns, such as traffic jams, accidents, dangerous driving and other abnormal behaviors. In this paper, a novel approach for traffic behavior modeling is presented for video-based road surveillance. The proposed system combines the pachinko allocation model (PAM) and support vector machine (SVM) for a hierarchical representation and identification of traffic behavior. A background subtraction technique using Gaussian mixture models (GMMs) and an object tracking mechanism based on Kalman filters are utilized to firstly construct the object trajectories. Then, the sparse features comprising the locations and directions of the moving objects are modeled by PAMinto traffic topics, namely activities and behaviors. As a key innovation, PAM captures not only the correlation among the activities, but also among the behaviors based on the arbitrary directed acyclic graph (DAG). The SVM classifier is then utilized on top to train and recognize the traffic activity and behavior. The proposed model shows more flexibility and greater expressive power than the commonly-used latent Dirichlet allocation (LDA) approach, leading to a higher recognition accuracy in the behavior classification. PMID- 26151214 TI - CoAP-Based Mobility Management for the Internet of Things. AB - Most of the current mobility management protocols such as Mobile IP and its variants standardized by the IETF may not be suitable to support mobility management for Web-based applications in an Internet of Things (IoT) environment. This is because the sensor nodes have limited power capacity, usually operating in sleep/wakeup mode in a constrained wireless network. In addition, sometimes the sensor nodes may act as the server using the CoAP protocol in an IoT environment. This makes it difficult for Web clients to properly retrieve the sensing data from the mobile sensor nodes in an IoT environment. In this article, we propose a mobility management protocol, named CoMP, which can effectively retrieve the sensing data of sensor nodes while they are moving. The salient feature of CoMP is that it makes use of the IETF CoAP protocol for mobility management, instead of using Mobile IP. Thus CoMP can eliminates the additional signaling overhead of Mobile IP, provides reliable mobility management, and prevents the packet loss. CoMP employs a separate location management server to keep track of the location of the mobile sensor nodes. In order to prevent the loss of important sensing data during movement, a holding mode of operation has been introduced. All the signaling procedures including discovery, registration, binding and holding have been designed by extending the IETF CoAP protocol. The numerical analysis and simulation have been done for performance evaluation in terms of the handover latency and packet loss. The results show that the proposed CoMP is superior to previous mobility management protocols, i.e., Mobile IPv4/v6 (MIPv4/v6), Hierarchical Mobile IPv4/v6 (HMIPv4/v6), in terms of the handover latency and packet loss. PMID- 26151215 TI - Providing IoT Services in Smart Cities through Dynamic Augmented Reality Markers. AB - Smart cities are expected to improve the quality of life of citizens by relying on new paradigms, such as the Internet of Things (IoT) and its capacity to manage and interconnect thousands of sensors and actuators scattered across the city. At the same time, mobile devices widely assist professional and personal everyday activities. A very good example of the potential of these devices for smart cities is their powerful support for intuitive service interfaces (such as those based on augmented reality (AR)) for non-expert users. In our work, we consider a scenario that combines IoT and AR within a smart city maintenance service to improve the accessibility of sensor and actuator devices in the field, where responsiveness is crucial. In it, depending on the location and needs of each service, data and commands will be transported by an urban communications network or consulted on the spot. Direct AR interaction with urban objects has already been described; it usually relies on 2D visual codes to deliver object identifiers (IDs) to the rendering device to identify object resources. These IDs allow information about the objects to be retrieved from a remote server. In this work, we present a novel solution that replaces static AR markers with dynamic markers based on LED communication, which can be decoded through cameras embedded in smartphones. These dynamic markers can directly deliver sensor information to the rendering device, on top of the object ID, without further network interaction. PMID- 26151216 TI - SNR Wall Effect Alleviation by Generalized Detector Employed in Cognitive Radio Networks. AB - The most commonly used spectrum sensing techniques in cognitive radio (CR) networks, such as the energy detector (ED), matched filter (MF), and others, suffer from the noise uncertainty and signal-to-noise ratio (SNR) wall phenomenon. These detectors cannot achieve the required signal detection performance regardless of the sensing time. In this paper, we explore a signal processing scheme, namely, the generalized detector (GD) constructed based on the generalized approach to signal processing (GASP) in noise, in spectrum sensing of CR network based on antenna array with the purpose to alleviate the SNR wall problem and improve the signal detection robustness under the low SNR. The simulation results confirm our theoretical issues and effectiveness of GD implementation in CR networks based on antenna array. PMID- 26151217 TI - A Novel Permanent Magnetic Angular Acceleration Sensor. AB - Angular acceleration is an important parameter for status monitoring and fault diagnosis of rotary machinery. Therefore, we developed a novel permanent magnetic angular acceleration sensor, which is without rotation angle limitations and could directly measure the instantaneous angular acceleration of the rotating system. The sensor rotor only needs to be coaxially connected with the rotating system, which enables convenient sensor installation. For the cup structure of the sensor rotor, it has a relatively small rotational inertia. Due to the unique mechanical structure of the sensor, the output signal of the sensor can be directed without a slip ring, which avoids signal weakening effect. In this paper, the operating principle of the sensor is described, and simulated using finite element method. The sensitivity of the sensor is calibrated by torsional pendulum and angle sensor, yielding an experimental result of about 0.88 mV/(rad.s(-2)). Finally, the angular acceleration of the actual rotating system has been tested, using both a single-phase asynchronous motor and a step motor. Experimental result confirms the operating principle of the sensor and indicates that the sensor has good practicability. PMID- 26151218 TI - Rapid adaptive radiation and host plant conservation in the Hawaiian picture wing Drosophila (Diptera: Drosophilidae). AB - The Hawaiian picture wing Drosophila are a striking example of adaptive radiation in specialist saprophages on an island system. We use DNA sequences from five nuclear genes with a total of 4260 nucleotides to provide a comprehensive phylogeny and biogeographic analysis of 90 species in the Hawaiian Drosophila picture wing clade. The current analysis indicates that the evolution of the picture wing clade took place more recently than previously suggested. The relationships of several morphologically anomalous taxa are resolved with strong support. Biogeography and host plant analyses show two periods of rapid divergence occurred when Kauai and Oahu were the main high islands, indicating that a combination of complex topographical features of islands and development of novel host plant associations was key to the rapid diversification of these lineages. For the past 2 million years, host associations within lineages have been largely stable, and speciation has occurred primarily due to the establishment of populations on newer islands as they arose followed by divergence by isolation. The existence of several apparently relictual taxa suggests that extinction has also played a major role in assembly of the present Hawaiian Drosophila fauna. PMID- 26151219 TI - Molecular phylogeography of canine distemper virus: Geographic origin and global spreading. AB - Canine distemper virus (CDV) (Paramyxoviridae-Morbillivirus) is a worldwide spread virus causing a fatal systemic disease in a broad range of carnivore hosts. In this study we performed Bayesian inferences using 208 full-length hemagglutinin gene nucleotide sequences isolated in 16 countries during 37 years (1975-2011). The estimated time to the most recent common ancestor suggested that current CDV strains emerged in the United States in the 1880s. This ancestor diversified through time into two ancestral clades, the current America 1 lineage that recently spread to Asia, and other ancestral clade that diversified and spread worldwide to originate the remaining eight lineages characterized to date. The spreading of CDV was characterized by several migratory events with posterior local differentiation, and expansion of the virus host range. A significant genetic flow between domestic and wildlife hosts is displayed; being domestic hosts the main viral reservoirs worldwide. This study is an extensive and integrative description of spatio/temporal population dynamics of CDV lineages that provides a novel evolutionary paradigm about the origin and dissemination of the current strains of the virus. PMID- 26151220 TI - Mountains and refuges: Genetic structure and evolutionary history in closely related, endemic Centaurea in continental Greece. AB - Mountains of continental Greece are one of the main Mediterranean biodiversity hotspots, very rich in endemic species. The speciation in this area might have resulted from two main factors: a complex orography and its role as a refugium during past glaciations. We have investigated genetic diversity and population structure for a group of narrow endemics of Centaurea subsect. Phalolepis, with three main goals: to investigate population structure of these narrow endemics, to check whether patterns of genetic variation are in agreement with recognized species boundaries, and to get insights into the process of diversification within this group. Fifteen populations belonging to seven species were genotyped using cpDNA (rpl32-trnL region) sequences and nuclear microsatellites (eight loci). SSR were used to assess genetic variability, to analyse molecular variance, to identify genetic barriers, to estimate recent and historical gene flow, and to carry out a model-based Bayesian clustering. Analysis of cpDNA was used to construct a haplotype network. Despite being narrow endemics, all the studied species show moderate to high SSR genetic diversity. Genetic isolation of populations is very high, with no current gene flow among them. Patterns of genetic structure indicate that there are more genetic clusters than there are currently recognized taxa. Genetic data suggest that isolation in mountain ranges and subsequent allopatric speciation would be the main driver of diversification in the group; the refugial nature of the mountains of continental Greece has allowed the maintenance of high within-population genetic diversity. PMID- 26151221 TI - Climate change-related migration and infectious disease. AB - Anthropogenic climate change will have significant impacts on both human migration and population health, including infectious disease. It will amplify and alter migration pathways, and will contribute to the changing ecology and transmission dynamics of infectious disease. However there has been limited consideration of the intersections between migration and health in the context of a changing climate. This article argues that climate-change related migration - in conjunction with other drivers of migration - will contribute to changing profiles of infectious disease. It considers infectious disease risks for different climate-related migration pathways, including: forced displacement, slow-onset migration particularly to urban-poor areas, planned resettlement, and labor migration associated with climate change adaptation initiatives. Migration can reduce vulnerability to climate change, but it is critical to better understand and respond to health impacts - including infectious diseases - for migrant populations and host communities. PMID- 26151222 TI - Isolation of Bioactive Compounds from Sunflower Leaves (Helianthus annuus L.) Extracted with Supercritical Carbon Dioxide. AB - The work described herein is a continuation of our initial studies on the supercritical fluid extraction (SFE) with CO2 of bioactive substances from Helianthus annuus L. var. Arianna. The selected SFE extract showed high activity in the wheat coleoptile bioassay, in Petri dish phytotoxicity bioassays, and in the hydroponic culture of tomato seeds. Chromatographic fractionations of the extracts and a spectroscopic analysis of the isolated compounds showed 52 substances belonging to 10 different chemical classes, which were mainly sesquiterpene lactones, diterpenes, and flavonoids. Heliannuol M (31), helivypolides K and L (36, 37), and helieudesmanolide B (38) are described for the first time in the literature. Metabolites have been tested in the etiolated wheat coleoptile bioassay with good results in a noteworthy effect on germination. The most active compounds were also tested on tomato seeds, heliannuol A (30) and leptocarpin (45) being the most active, with values similar to those of the commercial herbicide. PMID- 26151223 TI - Loss of marginal zone B-cells in SHIVSF162P4 challenged rhesus macaques despite control of viremia to low or undetectable levels in chronic infection. AB - Marginal zone (MZ) B cells generate T-independent antibody responses to pathogens before T-dependent antibodies arise in germinal centers. They have been identified in cynomolgus monkeys and monitored during acute SIV infection, yet have not been well-studied in rhesus macaques. Here we characterized rhesus macaque MZ B cells, present in secondary lymphoid tissue but not peripheral blood, as CD19(+), CD20(+), CD21(hi), IgM(+), CD22(+), CD38(+), BTLA(+), CD40(+), CCR6(+) and BCL-2(+). Compared to healthy macaques, SHIVSF162P4-infected animals showed decreased total B cells and MZ B cells and increased MZ B cell Ki-67 expression early in chronic infection. These changes persisted in late chronic infection, despite viremia reductions to low or undetectable levels. Expression levels of additional phenotypic markers and RNA PCR array analyses were in concert with continued low-level activation and diminished function of MZ B cells. We conclude that MZ B-cell dysregulation and dysfunction associated with SIV/HIV infection are not readily reversible. PMID- 26151224 TI - Genetics, diagnosis and management of colorectal cancer (Review). AB - Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. Surgery represents the mainstay of treatment in early cases but often patients are primarily diagnosed in an advanced stage of disease and sometimes also distant metastases are present. Neoadjuvant therapy is therefore needed but drug resistance may influence response and concur to recurrent disease. At molecular level, it is a very heterogeneous group of diseases with about 30% of hereditary or familial cases. During colorectal adenocarcinomas development, epithelial cells from gastrointestinal trait acquire sequential genetic and epigenetic mutations in specific oncogenes and/or tumour suppressor genes, causing CRC onset, progression and metastasis. Molecular characterization of cancer associated mutations gives valuable information about disease prognosis and response to the therapy. Very early diagnosis and personalised care, as well as a better knowledge of molecular basis of its onset and progression, are therefore crucial to obtain a cure of CRC. In this review, we describe updated genetics, current diagnosis and management of CRC pointing out the extreme need for a multidisciplinary approach to achieve the best results in patient outcomes. PMID- 26151225 TI - The novel function of JADE1S in cytokinesis of epithelial cells. AB - JADE1 belongs to a small family of PHD zinc finger proteins that interacts with histone acetyl transferase (HAT) HBO1 and is associated with chromatin. We recently reported JADE1 chromatin shuttling and phosphorylation during G2/M to G1 transition, which was sensitive to Aurora A inhibition. In the current study we examined mechanisms of the cell cycle regulation by the small isoform of JADE1 protein, JADE1S, and report data showing that JADE1S has a novel function in the regulation of cytokinesis. Using FACS assays, we show that, JADE1S depletion facilitated rates of G1-cells accumulation in synchronously dividing HeLa cell cultures. Depletion of JADE1S protein in asynchronously dividing cells decreased the proportion of cytokinetic cells, and increased the proportion of multi nuclear cells, indicative of premature and failed cytokinesis. In contrast, moderate overexpression of JADE1S increased the number of cytokinetic cells in time- and dose- dependent manner, indicating cytokinetic delay. Pharmacological inhibition of Aurora B kinase resulted in the release of JADE1S-mediated cytokinetic delay and allowed progression of abscission in cells over-expressing JADE1S. Finally, we show that JADE1S protein localized to centrosomes in interphase and mitotic cells, while during cytokinesis JADE1S localized to the midbody. Neither JADE1L nor partner of JADE1, HAT HBO1 was localized to the centrosomes or midbodies. Our study identifies the novel role for JADE1S in regulation of cytokinesis and suggests function in Aurora B kinase-mediated cytokinesis checkpoint. PMID- 26151227 TI - Impact of Enhanced Ozone Deposition and Halogen Chemistry on Tropospheric Ozone over the Northern Hemisphere. AB - Fate of ozone in marine environments has been receiving increased attention due to the tightening of ambient air quality standards. The role of deposition and halogen chemistry is examined through incorporation of an enhanced ozone deposition algorithm and inclusion of halogen chemistry in a comprehensive atmospheric modeling system. The enhanced ozone deposition treatment accounts for the interaction of iodide in seawater with ozone and increases deposition velocities by 1 order of magnitude. Halogen chemistry includes detailed chemical reactions of organic and inorganic bromine and iodine species. Two different simulations are completed with the halogen chemistry: without and with photochemical reactions of higher iodine oxides. Enhanced deposition reduces mean summer-time surface ozone by ~3% over marine regions in the Northern Hemisphere. Halogen chemistry without the photochemical reactions of higher iodine oxides reduces surface ozone by ~15% whereas simulations with the photochemical reactions of higher iodine oxides indicate ozone reductions of ~48%. The model without these processes overpredicts ozone compared to observations whereas the inclusion of these processes improves predictions. The inclusion of photochemical reactions for higher iodine oxides leads to ozone predictions that are lower than observations, underscoring the need for further refinement of the halogen emissions and chemistry scheme in the model. PMID- 26151228 TI - Analysis of the incidence fungi in a crypt cemetery. AB - The aim of this study was to analyze the incidence of fungi in the chapel crypt. The MAS 100 was used to monitor the air pollution. The lowest numbers of fungal colonies were isolated at the entrance to the cemetery (2400 CFU/m3). The outside temperature ranged from 24.5oC to 28.1oC, and relative humidity was between 35.3% and 46.4 %. The highest of fungal colonies from air samples at baseline were isolated inside the crypt when coffin was opened (4820 CFU/m3). The temperature in the crypt at baseline varied between 19.6 degrees C and 25.6 degrees C and humidity was between 50.8% and 60.1%. The number of fungal colonies increased significantly at the end of the study. Ten species of fungi were isolated from air samples inside and outside the chapel, and seven species of fungi were isolated on the surface of the exterior and interior of the chapel. Thirteen types/species of fungus were isolated from air samples collected in the crypt; 15 species of fungi were isolated on the walls, surface of the coffin, bones and other objects. Assessment of fungi in the air samples and different surfaces of the crypt, it revealed very high levels of molds in the air samples. IMPLICATIONS: Assessment of fungi in the air samples and different surfaces of the crypt revealed high levels of molds in the air samples. Fungal numbers within the crypt exceed recommended limits for occupational exposure. Employees working in the crypts should know about these hazards. PMID- 26151226 TI - Gut-liver axis, nutrition, and non-alcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called "gut-liver axis", play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host's metabolism contributing to NAFLD development. PMID- 26151229 TI - Correction to "An Investigation on the Fundamental Interaction Between Abeta Peptides and the AT-Rich DNA". PMID- 26151230 TI - Oxidative mechanisms of biological activity of low-intensity radiofrequency radiation. AB - This review aims to cover experimental data on oxidative effects of low-intensity radiofrequency radiation (RFR) in living cells. Analysis of the currently available peer-reviewed scientific literature reveals molecular effects induced by low-intensity RFR in living cells; this includes significant activation of key pathways generating reactive oxygen species (ROS), activation of peroxidation, oxidative damage of DNA and changes in the activity of antioxidant enzymes. It indicates that among 100 currently available peer-reviewed studies dealing with oxidative effects of low-intensity RFR, in general, 93 confirmed that RFR induces oxidative effects in biological systems. A wide pathogenic potential of the induced ROS and their involvement in cell signaling pathways explains a range of biological/health effects of low-intensity RFR, which include both cancer and non cancer pathologies. In conclusion, our analysis demonstrates that low-intensity RFR is an expressive oxidative agent for living cells with a high pathogenic potential and that the oxidative stress induced by RFR exposure should be recognized as one of the primary mechanisms of the biological activity of this kind of radiation. PMID- 26151231 TI - Development of Quinoline-2,4(1H,3H)-diones as Potent and Selective Ligands of the Cannabinoid Type 2 Receptor. AB - The cannabinoid type 2 receptors (CB2Rs) play crucial roles in inflammatory diseases. There has been considerable interest in developing potent and selective ligands for CB2R. In this study, quinoline-2,4(1H,3H)-dione analogs have been designed, synthesized, and evaluated for their potencies and binding properties toward the cannabinoid type 1 receptor (CB1R) and CB2R. C5- or C8-substituted quinoline-2,4(1H,3H)-diones demonstrate CB2R agonist activity, while the C6- or C7-substituted analogs are antagonists of CB2R. In addition, oral administration of 21 dose-dependently alleviates the clinical symptoms of experimental autoimmune encephalomyelitis in a mouse model of multiple sclerosis and protects the central nervous system from immune damage. Furthermore, the interaction modes predicted by docking simulations and the 3D-QSAR model generated with CoMFA may offer guidance for further design and modification of CB2R modulators. PMID- 26151232 TI - Impact of disability and other physical health issues on academic outcomes among American Indian and Alaskan Native college students: an exploratory analysis. AB - This study investigated whether self-identified disabilities among American Indian and Alaskan Native college students impact academic performance and persistence to graduation and explored the differences in health and academic grades between American Indian and Alaskan Native students and students of other racial and ethnic identities using the National College Health Assessment. Findings indicate that American Indian or Alaskan Native students have significantly lower grades than White and Asian students, and American Indian and Alaskan Native women report the highest incidence of health problems of any demographic group. Exploratory results point to future research to determine the full impact of disabilities and poor health on academic success. PMID- 26151234 TI - Erratum. PMID- 26151233 TI - Evaluation of Severe Combined Immunodeficiency and Combined Immunodeficiency Pediatric Patients on the Basis of Cellular Radiosensitivity. AB - Pediatric patients with severe or nonsevere combined immunodeficiency have increased susceptibility to severe, life-threatening infections and, without hematopoietic stem cell transplantation, may fail to thrive. A subset of these patients have the radiosensitive (RS) phenotype, which may necessitate conditioning before hematopoietic stem cell transplantation, and this conditioning includes radiomimetic drugs, which may significantly affect treatment response. To provide statistical criteria for classifying cellular response to ionizing radiation as the measure of functional RS screening, we analyzed the repair capacity and survival of ex vivo irradiated primary skin fibroblasts from five dysmorphic and/or developmentally delayed pediatric patients with severe combined immunodeficiency and combined immunodeficiency. We developed a mathematical framework for the analysis of gamma histone 2A isoform X foci kinetics to quantitate DNA-repair capacity, thus establishing crucial criteria for identifying RS. The results, presented in a diagram showing each patient as a point in a 2D RS map, were in agreement with findings from the assessment of cellular RS by clonogenic survival and from the genetic analysis of factors involved in the nonhomologous end-joining repair pathway. We provide recommendations for incorporating into clinical practice the functional assays and genetic analysis used for establishing RS status before conditioning. This knowledge would enable the selection of the most appropriate treatment regimen, reducing the risk for severe therapy-related adverse effects. PMID- 26151235 TI - College Students' Perceptions of Professor/Instructor Bullying: Questionnaire Development and Psychometric Properties. AB - OBJECTIVE: This study developed and examined the psychometric properties of a newly formed measure designed to assess professor/instructor bullying, as well as teacher bullying occurring prior to college. Additionally, prevalence of instructor bullying and characteristics related to victims of instructor bullying were examined. PARTICIPANTS: Participants were 337 college students recruited in 2012 from a northeastern university. METHODS: An online questionnaire was administered to college students. A split-half, cross-validation approach was employed for measurement development. RESULTS: The measure demonstrated strong criterion validity and internal consistency. Approximately half of students reported witnessing professor/instructor bullying and 18% reported being bullied by a professor/instructor. Report of teacher bullying occurring prior to college was related to professor/instructor bullying in college, and sex was a moderating variable. CONCLUSION: College students perceive instructor bullying as occurring but may not know how to properly address it. Prevention efforts should be made by university administrators, faculty, and staff. PMID- 26151236 TI - Age-related Changes of Posterior Tibial Slope and Its Roles in Anterior Cruciate Ligament Injury. AB - Nearly all previous studies in posterior tibial slope (PTS) and anterior cruciate ligament (ACL) injuries ignored age-related changes, and the published data are inconsistent. The objective of this study was to reveal age-related changes of PTS and its roles in ACL injury. Data for 2618 lower limbs were included initially based on the availability of lateral radiographs and a suitable femoro tibial angle. The final 1431 subjects were analyzed according to age, gender, side, and injury status. Student's t-tests, one-way analysis of variance, and curve fitting were used to analyze data. The PTS in males was greater than that in females in the 0-9 and 30-39-year-old groups, but this pattern reversed in the 40-49, 60-69, 70-79, and 80-89-year-old groups. The PTS was greater on the left side than on the right side in the 0-9, 10-19, 50-59, 60-69, and 80-89-year-old groups. The curve fitting for PTS demonstrated a trend of first decreasing and then increasing with aging. The PTS values differed significantly between knees with an ACL injury and those without in the 20-29, 30-39, and 40-49-year-old groups but not in the 50-59-year-old group. The PTS follows a trend of first decreasing and then increasing, and its role in ACL injury changes with advancing age. The higher PTS is only unrelated to the risk of ACL injury in age groups with a lower mean PTS value. PMID- 26151239 TI - Exploring routes to tailor the physical and chemical properties of oxides via doping: an STM study. AB - Doping opens fascinating possibilities for tailoring the electronic, optical, magnetic, and chemical properties of oxides. The dopants perturb the intrinsic behavior of the material by generating charge centers for electron transfer into adsorbates, by inducing new energy levels for electronic and optical excitations, and by altering the surface morphology and hence the adsorption and reactivity pattern. Despite a vivid scientific interest, knowledge on doped oxides is limited when compared to semiconductors, which reflects the higher complexity and the insulating nature of many oxides. In fact, atomic-scale studies, aiming at a mechanistic understanding of dopant-related processes, are still scarce.In this article, we review our scanning tunneling microscopy (STM) experiments on thin, crystalline oxide films with a defined doping level. We demonstrate how the impurities alter the surface morphology and produce cationic/anionic vacancies in order to keep the system charge neutral. We discuss how individual dopants can be visualized in the lattice, even if they reside in subsurface layers. By means of STM-conductance and x-ray photoelectron spectroscopy, we determine the electronic impact of dopants, including the energies of their eigen states and local band bending effects in the host oxide. Electronic transitions between dopant-induced gap states give rise to new optical modes, as detected with STM luminescence spectroscopy. From a chemical perspective, dopants are introduced to improve the redox potential of oxide materials. Electron transfer from Mo-donors, for example, alters the growth behavior of gold and activates O2 molecules on a wide gap CaO surface. Such results demonstrate the enormous potential of doped oxides in heterogeneous catalysis. Our experiments address the issue of doping from a fundamental viewpoint, posing questions on the lattice position, charge state, and electron-transfer potential of the impurity ions. Whether doped oxides are suitable to catalyze surface reactions needs to be explored in more applied studies in the future. PMID- 26151237 TI - Skin absorption and human exposure estimation of three widely discussed UV filters in sunscreens--In vitro study mimicking real-life consumer habits. AB - Due to health concerns about safety, three UV-filters (Benzophenone-3, BP3, 10%; Ethylhexyl Methoxycinnamate, EHMC, 10%; Butyl Methoxydibenzoylmethane, BMDBM; 5%) were examined in vitro for absorption on full-thickness pig-ear skin, mimicking human in-use conditions. Kinetic profiles confirmed the rapid permeation of BP3; after the first hour of skin (frozen-stored) exposure to 2 mg/cm(2) (W/O sunscreen; recommended but unrealistic amount), about 0.5% of the applied dose passed into the receptor fluid. The absorption rate of filters was higher from W/O than from O/W emulsions. The fresh/frozen-stored skin permeability coefficient (0.83-0.54) for each UV filter was taken into account. Systemic Exposure Dosage of BP3, EHMC, BMDBM for humans as a consequence of (i) whole-body and (ii) face treatment with 0.5 mg/cm(2) of W/O sunscreen for 6-h skin exposure followed by washing and subsequent 18-h permeation (a realistic scenario) were estimated to be (i) 4744, 1032 and 1036 MUg/kg-bw/day, and (ii) 153, 33 and 34 MUg/kg-bw/day, respectively. From Margin of Safety for BP3, EHMC and BMDBM (i) 42, 485 and 192 as well as (ii) 1307; 15,151 and 5882, respectively, only the value of 42 (<100) for BP3 indicated a possible health risk. Escalation of a phobia towards all organic UV filters is undesirable. PMID- 26151238 TI - Cellular Uptake and Ultrastructural Localization Underlie the Pro-apoptotic Activity of a Hydrocarbon-stapled BIM BH3 Peptide. AB - Hydrocarbon stapling has been applied to restore and stabilize the alpha-helical structure of bioactive peptides for biochemical, structural, cellular, and in vivo studies. The peptide sequence, in addition to the composition and location of the installed staple, can dramatically influence the properties of stapled peptides. As a result, constructs that appear similar can have distinct functions and utilities. Here, we perform a side-by-side comparison of stapled peptides modeled after the pro-apoptotic BIM BH3 helix to highlight these principles. We confirm that replacing a salt-bridge with an i, i + 4 hydrocarbon staple does not impair target binding affinity and instead can yield a biologically and pharmacologically enhanced alpha-helical peptide ligand. Importantly, we demonstrate by electron microscopy that the pro-apoptotic activity of a stapled BIM BH3 helix correlates with its capacity to achieve cellular uptake without membrane disruption and accumulate at the organellar site of mechanistic activity. PMID- 26151240 TI - Caesarean section at maternal request--the differing views of patients and healthcare professionals: a questionnaire based study. AB - OBJECTIVE: The number of caesarean sections at maternal request without medical indication is increasing. We aimed to explore the views of pregnant women, midwives and doctors using six hypothetical clinical scenarios and compare group views on: (a) perceived appropriateness of requests for caesarean section and (b) the reasons underlying these requests. STUDY DESIGN: A questionnaire was distributed to 166 pregnant women, 31 midwives and 52 doctors within maternity units at two hospitals in the North East region of England. Six hypothetical clinical scenarios for maternal requests were used: (1) uncomplicated first pregnancy, (2) one previous normal delivery, (3) one previous instrumental delivery, (4) one previous caesarean section, (5) one previous caesarean section with vaginal delivery since and (6) uncomplicated twin pregnancy. To highlight the differences in group responses, two main questions were asked for each scenario: 1. Should women be able to request a caesarean section? 2. What do you feel are the reasons for requesting a caesarean section? Data was analysed using Chi-squared or likelihood ratio as appropriate. RESULTS: In scenarios 1-3, professional groups were 'less likely' than pregnant women to always support a request (2.4% vs. 19.4%), (2.6% vs. 15.6%), (4.6% vs. 22%), (p<0.001). No significant differences were shown between doctors and midwives except for scenario 6 (twins), where midwives more often felt maternal requests should be declined (26.1% vs. 1.9%) (p=0.001). Multiparous women (n=95) were more likely to agree 'sometimes' to maternal requests in scenarios 1, compared to nulliparous women (n=71) (21.1% vs. 4.2%) (p=0.04). 'Safety of the baby' was ranked highly with pregnant women in scenarios 1-3 (mean 24.4%, range [15.8-38%]) compared with healthcare professionals (7.6% [3.4-12.8%]). However in scenario 3, healthcare professionals attributed 'fear of injury to self' (29.6%) as the most likely reason compared to 14.6% of pregnant women. CONCLUSION: Healthcare professionals and pregnant women's views differ significantly. Multiparous patients' views differ from those who have not had children before. We should provide clearer information on risks and benefits which encompass areas that concern women most. PMID- 26151241 TI - Overexpression of microRNA-125a-3p effectively inhibits the cell growth and invasion of lung cancer cells by regulating the mouse double minute 2 homolog/p53 signaling pathway. AB - MicroRNAs (miRs) are a family of small non-coding RNAs that are 21-24 nucleotides in length. Decreased expression of hsa-miR-125a-3p is observed in a number of patients with non-small cell lung cancer; however, it is not clear how this miRNA regulates the growth and invasion of lung tumor cells. The aim of the present study was to identify the function of hsa-miR-125a-3p in the growth and invasion of lung cancer cells. The expression of hsa-miR-125a-3p in the A549, NCI-H460 and SPCA-1 lung cancer cell lines was analyzed by reverse transcription-quantitative polymerase chain reaction and the human bronchiolar epithelium cell line (HBE) was used as a control. The results demonstrated that the expression of hsa-miR 125a-3p was significantly lower in NCI-H460, A549 and SPCA-1 cells, compared with that in HBE cells. Overexpression of sense miR-125a-3p in the A549 lung cancer cell line inhibited cell proliferation for 5-7 days (P<0.01), and transfection of antisense miR-125a-3p did not suppress the cell growth of the lung cancer cells. In addition, overexpression of miR-125a-3p in the NCI-H460 lung cancer cell line markedly induced cell apoptosis, which was detected by fluorescence-activated cell sorting with annexin V-fluorescein isothiocyanate/propidium iodide staining. The results of the Transwell migration assay also revealed that transfection of miR-125a-3p resulted in decreased migration of lung cancer tumor cells. The pro apoptotic gene p53 expression was detected by western blot analysis. The results revealed that the expression of mouse double minute (MDM)-2 homolog, the principal cellular antagonist of p53, was decreased and p53 expression was upregulated in sense has-miR-125a-3p transfected A549 cells. This was consistent with that observed in NCI-H460 cells, suggesting that hsa-miR-125a-3p may be involved in the regulation of the MDM2/p53 signaling pathway in lung cancer cells. In conclusion, overexpression of hsa-miR-125a-3p significantly inhibited the proliferation and invasion of lung cancer cells, which may aid in determining the mechanisms underlying the development of lung cancer. PMID- 26151242 TI - Evaluation of anti-asthmatic and antioxidant potential of Boerhavia procumbens in toluene diisocyanate (TDI) treated rats. AB - AIM OF THE STUDY: Asthma is an ailment of airways characterized by activation of the T helper (Th) 2 lymphocytes and subsequent movement of inflammatory cells. Boerhavia procumbens of family Nyctaginaceae is locally used for the treatment of asthma, cough, hemorrhoids, dropsy, cardiac, eyes and kidney problems. We have evaluated its methanol extract (BPM) as a therapeutic candidate for asthma against toluene diisocyanate (TDI) allergic model in rat. The BPM extract was obtained from the whole plant of B. procumbens in methanol. Sprague-Dawley male 36 rats (200-250 g) were categorized into 6 groups having six rats in each category. The animals were provoked (10%) and sensitized (5%) by TDI. Animals of groups I-III were vehicle control (ethyl acetate), diseased control (TDI) and reference control (TDI+dexamethasone {2.5mg/kg bw}), respectively. Animals of group IV (TDI+200mg/kg bw) and group V (TDI+400mg/kg bw) were administered with BPM whereas group VI was administered with 400mg/kg bw alone of BPM. Protective effects of BPM were determined by counting the number of leucocytes and estimation of interleukines in blood, bronchoalveolar lavage (BAL) and in in vitro culture of spleen cells. Estimation of antioxidant enzymes, lipid peroxides and H2O2 and histopathology of lungs were carried out for antioxidant potential of plant extract used. RESULTS: Methanol extract of B. procumbens suppressed the asthmatic symptoms and inhibited the infiltration of eosinophils and lymphocytes in lungs of TDI provoked rats. Administration of BPM to TDI provoked rats, dose dependently, inhibited the release of interleukins (IL)-2 in serum and IL-4, IL-6 interferon gamma (IFN-gamma) in bronchoalveolar lavage (BAL) and in in vitro culture of spleen cells, and ameliorated the oxidative stress in lung tissues. Quantitative scoring of the lung histopathology exhibited protective effects of BPM and the inflammation, mucus, thickening of peribronchial smooth muscle layer and subepithelial deposition of collagen induced with TDI were ameliorated. The BPM has the anti-inflammatory properties that may be used to treat the asthma and inflammatory related ailments. PMID- 26151243 TI - Polytrichum commune L.ex Hedw ethyl acetate extract-triggered perturbations in intracellular Ca2+ homeostasis regulates mitochondrial-dependent apoptosis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Polytrichum commune L.ex Hedw (PCLH), a moss of Bryopsida, has been used as a traditional Chinese medicine and shown to possess anticancer activities. Previous studies have indicated its anti-leukemia effect but the potential mechanisms have not been fully explained. AIM OF THE STUDY: The present study aimed to further investigate the efficacy of PCLH ethyl acetate fraction (PC-EEF) and the associated mechanisms in human leukemia cells. MATERIALS AND METHODS: Phytochemical analysis of PC-EEF was performed by spectrophotometry and HPLC. MTT analysis and trypan blue exclusion assay were adopted to examine its cytotoxicity on a panel of leukemia cells (K562, U937, HL 60 and K562/DOX cells) and non-cancerous cells (human PBMCs). Anti-proliferative effect was monitored by colony formation assay and EdU incorporation assay. Ultrastructural alterations on K562 cell membrane surface were observed by scanning electron microscopy. Changes on plasma membrane integrity, cell membrane potential, mitochondrial membrane potential and apoptosis were analyzed by flow cytometry. Fluorescence microscope was performed to assess [Ca(2+)]i level, mitochondrial injury and cytochrome c release. Apoptosis-associated protein expression was analyzed by western blot. The role of Ca(2+) in PC-EEF-induced cell death was investigated by Ca(2+) chelating reagent BAPTA-AM. RESULTS: PC-EEF possessed relatively high flavonoid content (about 88.84 +/- 0.89%) and showed significant cytotoxicity to human leukemia cells. PC-EEF could cause obvious cell morphological deformation, membrane integrity loss and membrane depolarization. Meanwhile, PC-EEF treatment could dramatically potentiate perturbations in cellular Ca(2+) homeostasis. Subsequently, mitochondrial membrane potential (MMP) collapse, cytochrome c release and Bcl-2/Bax down-regulation were all observed. Consistent with these results, PC-EEF treatment resulted in significant activation of caspase 3, poly (ADP-ribose) polymerase (PARP) degradation and apoptosis. Moreover, PC-EEF-caused cytotoxicity, membrane damage, mitochondrial injury and apoptosis were remarkably reversed by BAPTA-AM. CONCLUSIONS: PC-EEF damaged the membrane system and triggered Ca(2+)-dependent mitochondrial apoptosis, which may provide some new insights into its efficacy against human leukemia cells. PMID- 26151244 TI - The efficacy of whey associated with dodder seed extract on moderate-to-severe atopic dermatitis in adults: A randomized, double-blind, placebo-controlled clinical trial. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis is a common chronic inflammatory skin condition that is on the rise and adversely affects quality of life of the affected individual. Dry skin and pruritus, major characteristics of this disease, are associated with the dysfunction of the skin barrier. Though mild cases of the disease can be controlled with antihistamines and topical corticosteroids, moderate-to-severe cases often require treatment with immunomodulatory drugs, which have many side effects. It is now more common to use complementary and alternative medicines in the treatment of atopic dermatitis. In traditional Iranian medicine, the use of whey with the aqueous extract of field dodder (Cuscuta campestris Yunck.) seeds in severe and refractory cases of atopic dermatitis is common and has no side effects. The aim of this study was to assess the efficacy and safety of whey associated with dodder seed extract in the treatment of moderate-to-severe atopic dermatitis in adults. MATERIALS AND METHODS: The study was a randomized, double-blind placebo control trial that was conducted on 52 patients with moderate-to-severe atopic dermatitis for 30 days. In this study patients received freeze dried whey powder with spray dried water extract of field dodder or the placebo for 15 days. At baseline (week zero), after the end of the 15 day treatment period (week three) and 15 days after stopping the drug or placebo (follow-up/week five), patients were evaluated in terms of skin moisture, elasticity, pigmentation, surface pH and sebum content on the forearm with Multi Skin Test Center(r) MC1000 (Courage & Khazaka, Germany) and the degree of pruritus and sleep disturbance in patients were also recorded. RESULTS: 42 patients completed 30 days of treatment with the medicine and the follow-up period. At the end of the follow-up period a significant increase in skin moisture and elasticity in the group receiving whey with dodder was observed compared with the placebo group (p<0.001). There was a significant difference between the two groups regarding the pruritus after 15 days of receiving treatment or the placebo (p<0.05), and at the end of the 30-day study period the difference was clearly significant (p<0.001). Sleep disturbance showed significant changes at the end of follow-up period (p<0.05). There was no significant difference between the two groups concerning changes in skin pigmentation, however, a significant decrease was observed in the group receiving whey associated with dodder seed extract over time (p<0.001). There were no significant alterations in skin surface pH and the amount of sebum between the two groups. Temporary side effects were reported including anorexia and mild gastrointestinal problems in drug use. It is noteworthy that in this study despite the fact that patients received whey with dodder for just 15 days, moisture and elasticity of the skin continued to increase in the second half of the study (follow-up period). This shows that the effect of whey with dodder is not transient and this drug really helped skin barrier reconstruction and accelerated the healing process of skin. This positively influenced the skin parameters and consequently the improvement of pruritus and sleep disturbance. CONCLUSIONS: The results indicate that whey associated with dodder seed extract can serve as a promising alternative for the treatment of moderate-to-severe atopic dermatitis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT2013121415790N1. PMID- 26151245 TI - Medicinal plants and finished marketed herbal products used in the treatment of malaria in the Ashanti region, Ghana. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical survey was performed to document medicinal plants employed in the management of malaria in the Bosomtwe and Sekyere East Districts of the Ashanti Region (Ghana), in comparison with the plant ingredients in herbal antimalarial remedies registered by the Ghana Food and Drug Administration. MATERIALS AND METHODS: Two hundred and three (203) herbalists from 33 communities within the two districts were interviewed on medicinal plants they use to manage malaria. A literature search was made to determine already documented plants. In addition, 23 finished marketed herbal products indicated for the management of malaria were identified and their labels examined to find out which of the plants mentioned in our survey were listed as ingredients and whether these products are in anyway regulated. RESULTS: Ninety eight (98) species of plants were cited for the management of malaria. In comparison with literature citations, 12 (12.2%) species were reported for the management of malaria for the first time and 20 (20.4%) others for the first time in Ghana. Twenty-three (23) finished marketed herbal antimalarial products examined contained aerial or underground parts of 29 of the plants cited in our survey as ingredients. Twenty-two (22) of these products have been registered by the Ghana Food and Drugs Authority, four (4) of which were included in the recommended herbal medicine list for treating malaria in Ghana. CONCLUSION: This study provides new additions to the inventory of medicinal plants used for the management of malaria and reports the commercial availability and regulation of finished marketed labelled herbal products intended for the treatment of malaria in Ghana. PMID- 26151246 TI - Displaced Tibial Shaft Fractures With Intact Fibula in Children: Nonoperative Management Versus Operative Treatment With Elastic Stable Intramedullary Nailing. AB - BACKGROUND: The main objective of this study was to retrospectively evaluate the clinical and radiographic outcomes of displaced tibial shaft fractures with intact fibula in children after nonoperative management and operative treatment by elastic stable intramedullary nailing. METHODS: A study was performed on 80 consecutive children, 56 males, 24 females from 2 Institutions, with displaced and closed tibial shaft fracture with intact fibula. All patients underwent regular clinical and radiographic follow-up visits for at least 2 years after injury. RESULTS: In total, 26 patients (group A-Institution I) were treated surgically by elastic stable intramedullary nailing and 54 patients (18 patients from group B-Institution I and 36 patients from group C-Institution II) were treated nonoperatively with closed reduction and casting. groups A, B, and C did not significantly differ on sex (P=0.37), side (P=0.54), and fracture site (P=0.14).Valgus deformity was significantly controlled in group A patients only (P=0.001); during follow-up in group B patients (P=0.017), and showed no significant change between pretreatment images and last follow-up in group C patients (P=0.71). Procurvatum deformity was significantly controlled in group A patients only (P=0.001); it showed no significant improvement after conservative treatment in group B (P=0.73) and C patients (P=0.8). Recurvatum was significantly improved in group A (P<0.001) and C patients (P<0.001) but remained unchanged in group B patients (P=0.15). Varus deformity improved significantly in all patient groups.Immobilization time was significantly shorter in group A compared with group B and C patients (P<0.001).However, numerical differences, although statistically significant, were not clinically relevant for all variables but immobilization time. CONCLUSIONS: This study showed good functional and radiologic outcomes in the pediatric population who had sustained closed, traumatic, displaced fracture of tibial diaphysis without associated fibula fracture.On the basis of the findings reported here, it is not contraindicated to operate skeletally immature patients with displaced fracture of tibial diaphysis without associated fibula fracture. However, results were essentially the same and either method is a satisfactory choice for pediatric tibia shaft fractures with an intact fibula. In particular, we found that conservative treatment was as efficacious as surgical treatment apart from the length of time for immobilization. LEVEL OF EVIDENCE: Level III. PMID- 26151249 TI - Garden of the Generalife in Granada: Theo van Rysselberghe. PMID- 26151250 TI - Varmus Returns to His Roots in Cancer Genetics. PMID- 26151251 TI - A Same-Sex Infertility Health Insurance Mandate in Maryland? PMID- 26151260 TI - Direct Reprogramming: Bypassing Stem Cells for Therapeutics. PMID- 26151261 TI - The Role of Physicians in the Era of Predictive Analytics. PMID- 26151262 TI - A PIECE OF MY MIND. Stopping Time. PMID- 26151263 TI - Stroke and Cognitive Decline. PMID- 26151264 TI - Six Months vs Extended Oral Anticoagulation After a First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial. AB - IMPORTANCE: The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain. OBJECTIVES: To determine the benefits and harms of an additional 18-month treatment with warfarin vs placebo, after an initial 6-month nonrandomized treatment period on a vitamin K antagonist. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers. INTERVENTIONS: Warfarin or placebo for 18 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. RESULTS: After randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; P = .001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05 0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42 month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups. CONCLUSIONS AND RELEVANCE: Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00740883. PMID- 26151265 TI - Trajectory of Cognitive Decline After Incident Stroke. AB - IMPORTANCE: Cognitive decline is a major cause of disability in stroke survivors. The magnitude of survivors' cognitive changes after stroke is uncertain. OBJECTIVE: To measure changes in cognitive function among survivors of incident stroke, controlling for their prestroke cognitive trajectories. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 23,572 participants 45 years or older without baseline cognitive impairment from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, residing in the continental United States, enrolled 2003-2007 and followed up through March 31, 2013. Over a median follow-up of 6.1 years (interquartile range, 5.0-7.1 years), 515 participants survived expert-adjudicated incident stroke and 23,057 remained stroke free. EXPOSURE: Time-dependent incident stroke. MAIN OUTCOMES AND MEASURES: The primary outcome was change in global cognition (Six-Item Screener [SIS], range, 0-6). Secondary outcomes were change in new learning (Consortium to Establish a Registry for Alzheimer Disease Word-List Learning; range, 0-30), verbal memory (Word-List Delayed Recall; range, 0-10), and executive function (Animal Fluency Test; range, >=0), and cognitive impairment (SIS score <5 [impaired] vs >=5 [unimpaired]). For all tests, higher scores indicate better performance. RESULTS: Stroke was associated with acute decline in global cognition (0.10 points [95% CI, 0.04 to 0.17]), new learning (1.80 points [95% CI, 0.73 to 2.86]), and verbal memory (0.60 points [95% CI, 0.13 to 1.07]). Participants with stroke, compared with those without stroke, demonstrated faster declines in global cognition (0.06 points per year faster [95% CI, 0.03 to 0.08]) and executive function (0.63 points per year faster [95% CI, 0.12 to 1.15]), but not in new learning and verbal memory, compared with prestroke slopes. Among survivors, the difference in risk of cognitive impairment acutely after stroke, compared with immediately before stroke, was not statistically significant (odds ratio, 1.32 [95% CI, 0.95 to 1.83]; P = .10); however, there was a significantly faster poststroke rate of incident cognitive impairment compared with the prestroke rate (odds ratio, 1.23 per year [95% CI, 1.10 to 1.38]; P < .001). For a 70-year-old black woman with average values for all covariates at baseline, stroke at year 3 was associated with greater incident cognitive impairment: absolute difference of 4.0% (95% CI, 1.2% to 9.2%) at year 3 and 12.4% (95% CI, 7.7% to 17.1%) at year 6. CONCLUSIONS AND RELEVANCE: Incident stroke was associated with an acute decline in cognitive function and also accelerated and persistent cognitive decline over 6 years. PMID- 26151268 TI - Long-term vs Short-term Therapy With Vitamin K Antagonists for Symptomatic Venous Thromboembolism. AB - CLINICAL QUESTION: Is long-term (>=3 months) vs short-term therapy with vitamin K antagonists (VKAs) associated with differences in the incidence of recurrent venous thromboembolism (VTE), major bleeding, and mortality in patients with symptomatic VTE? BOTTOM LINE: Long-term treatment with VKAs is associated with a reduced risk for recurrent VTE and an increased risk for major bleeding compared with short-term treatment in patients with VTE, but is not associated with differences in mortality. PMID- 26151267 TI - Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome. AB - IMPORTANCE: Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome). OBJECTIVE: To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry. Data were analyzed with a weighted cohort approach. Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand. EXPOSURES: Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use. MAIN OUTCOMES AND MEASURES: Self-reported diagnosis of endometrial cancer. RESULTS: Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, 0.29; 95% CI, 0.24 to 0.34). Endometrial cancer was diagnosed in 11% (n = 70) of women with age at menarche greater than or equal to 13 years compared with 12.6% (n = 57) of women with age at menarche less than 13 years (incidence rate per 100 person-years, 0.27 vs 0.31; rate difference, -0.04 [95% CI, -0.15 to 0.05]; hazard ratio per year, 0.85 [95% CI, 0.73 to 0.99]; P = .04). Endometrial cancer was diagnosed in 10.8% (n = 88) of parous women compared with 14.4% (n = 40) of nulliparous women (incidence rate per 100 person-years, 0.25 vs 0.43; rate difference, -0.18 [95% CI, -0.32 to -0.04]; hazard ratio, 0.21 [95% CI, 0.10 to 0.42]; P < .001). Endometrial cancer was diagnosed in 8.7% (n = 70) of women who used hormonal contraceptives greater than or equal to 1 year compared with 19.2% (n = 57) of women who used contraceptives less than 1 year (incidence rate per 100 person-years, 0.22 vs 0.45; rate difference, -0.23 [95% CI, -0.36 to -0.11]; hazard ratio, 0.39 [95% CI, 0.23 to 0.64]; P < .001). There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use. CONCLUSIONS AND RELEVANCE: For women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk. PMID- 26151270 TI - Edoxaban (Savaysa)--The Fourth New Oral Anticoagulant. PMID- 26151266 TI - Association of Cardiometabolic Multimorbidity With Mortality. AB - IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity. PMID- 26151269 TI - Computed Tomographic Pulmonary Angiography for Pulmonary Embolism. PMID- 26151271 TI - Trends in Management for Patients With Localized Prostate Cancer, 1990-2013. PMID- 26151272 TI - Discordant Interpretations of Breast Biopsy Specimens by Pathologists. PMID- 26151273 TI - Discordant Interpretations of Breast Biopsy Specimens by Pathologists. PMID- 26151274 TI - Discordant Interpretations of Breast Biopsy Specimens by Pathologists--Reply. PMID- 26151275 TI - Suicide Among US Military Personnel. PMID- 26151276 TI - Suicide Among US Military Personnel--Reply. PMID- 26151277 TI - Redefining Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. PMID- 26151278 TI - Redefining Myalgic Encephalomyelitis/Chronic Fatigue Syndrome--Reply. PMID- 26151279 TI - Incorrect Data in Table 4. PMID- 26151280 TI - Data Errors in Table 2. PMID- 26151281 TI - Data Errors in Table 3 and in Text. PMID- 26151282 TI - Data Errors in Results Section. PMID- 26151284 TI - Modern English Usage. PMID- 26151285 TI - JAMA PATIENT PAGE. Treatment Duration for Pulmonary Embolism. PMID- 26151286 TI - A novel role for xenopsin: Stimulation of food intake. AB - Xenopsin (XPN), an extract from frog skin, is comprised of 80 amino acids and exerts effects on the mammalian digestive tract. The purpose of the study presented here was to determine if XPN would affect food intake using chicks as models. Chicks which had been fasted for 180 min did not change food or water intake after central injection of XPN. However, ab libitum fed chicks which received 1 and 3 nmol central XPN increased food intake while water intake was not affected. When the dose was increased to 9 nmol chicks did not increase food intake but their water intake was reduced suggesting malaise. Chicks injected with XPN had increased c-Fos immunoreactivity in the lateral hypothalamus, but other hypothalamic appetite-associated nuclei were not affected. When XPN was directly injected into the lateral hypothalamus food intake was increased, suggesting a primary site of action. When the expression of appetite-associated neuropeptide mRNA was quantified chicks injected with XPN had increased proopiomelanocortin mRNA. Lastly, a comprehensive behavior analysis was performed and while XPN injected chicks had an increase in the number of feeding pecks, jumping, preening, deep rest and sitting were all decreased. Thus, we conclude that exogenous XPN functions as an orexigenic factor in chicks and its effects are mediated by the lateral hypothalamus. PMID- 26151287 TI - 3D Scaffolds with Different Stiffness but the Same Microstructure for Bone Tissue Engineering. AB - A growing body of evidence has shown that extracellular matrix (ECM) stiffness can modulate stem cell adhesion, proliferation, migration, differentiation, and signaling. Stem cells can feel and respond sensitively to the mechanical microenvironment of the ECM. However, most studies have focused on classical two dimensional (2D) or quasi-three-dimensional environments, which cannot represent the real situation in vivo. Furthermore, most of the current methods used to generate different mechanical properties invariably change the fundamental structural properties of the scaffolds (such as morphology, porosity, pore size, and pore interconnectivity). In this study, we have developed novel three dimensional (3D) scaffolds with different degrees of stiffness but the same 3D microstructure that was maintained by using decellularized cancellous bone. Mixtures of collagen and hydroxyapatite [HA: Ca10(PO4)6(OH)2] with different proportions were coated on decellularized cancellous bone to vary the stiffness (local stiffness, 13.00 +/- 5.55 kPa, 13.87 +/- 1.51 kPa, and 37.7 +/- 19.6 kPa; bulk stiffness, 6.74 +/- 1.16 kPa, 8.82 +/- 2.12 kPa, and 23.61 +/- 8.06 kPa). Microcomputed tomography (MU-CT) assay proved that there was no statistically significant difference in the architecture of the scaffolds before or after coating. Cell viability, osteogenic differentiation, cell recruitment, and angiogenesis were determined to characterize the scaffolds and evaluate their biological responses in vitro and in vivo. The in vitro results indicate that the scaffolds developed in this study could sustain adhesion and growth of rat mesenchymal stem cells (MSCs) and promote their osteogenic differentiation. The in vivo results further demonstrated that these scaffolds could help to recruit MSCs from subcutaneous tissue, induce them to differentiate into osteoblasts, and provide the 3D environment for angiogenesis. These findings showed that the method we developed can build scaffolds with tunable mechanical properties almost without variation in 3D microstructure. These preparations not only can provide a cell-free scaffold with optimal matrix stiffness to enhance osteogenic differentiation, cell recruitment, and angiogenesis in bone tissue engineering but also have significant implications for studies on the effects of matrix stiffness on stem cell differentiation in 3D environments. PMID- 26151288 TI - Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery. AB - Delivering a drug into and through the skin is of interest as the skin can act as an alternative drug administration route for oral delivery. The development of new delivery methods, such as microneedles, makes it possible to not only deliver small molecules into the skin, which are able to pass the outer layer of the skin in therapeutic amounts, but also macromolecules. To provide insight into the administration of these molecules into the skin, the aim of this study was to assess the transport of macromolecules within and between its various layers. The diffusion coefficients in the epidermis and several locations in the papillary and reticular dermis were determined for fluorescein dextran of 40 and 500 kDa using a combination of fluorescent recovery after photobleaching experiments and finite element analysis. The diffusion coefficient was significantly higher for 40 kDa than 500 kDa dextran, with median values of 23 and 9 um(2)/s in the dermis, respectively. The values only marginally varied within and between papillary and reticular dermis. For the 40 kDa dextran, the diffusion coefficient in the epidermis was twice as low as in the dermis layers. The adopted method may be used for other macromolecules, which are of interest for dermal and transdermal drug delivery. The knowledge about diffusion in the skin is useful to optimize (trans)dermal drug delivery systems to target specific layers or cells in the human skin. PMID- 26151289 TI - Unconstrained testing of spine with bi-axial universal testing machine. AB - BACKGROUND: In-vitro biomechanical assessment of the spine reveals significant information on the mechanics of spinal disorders, treatment methods, and surgical implants. Specialized devices for the evaluation of spine biomechanics have thus become popular. However, these devices might not be affordable for all research groups. PURPOSE: The purpose of this study was to describe an apparatus to be attached to a standard bi-axial universal testing machine that would make unconstrained testing of the spine possible. STUDY DESIGN/SETTING: A technical note on the definition of a spinal testing fixture with validation. METHODS: Intact lumbosacral spines (T12-S1) were tested in sagittal and lateral bending and axial rotation. Three-dimensional interlevel rotations at each level (L1-4) were analyzed. RESULTS: By comparison with the literature, we found that the new fixture was able to successfully produce reasonable relative rotation values for the lumbar spine. CONCLUSIONS: We demonstrated that the low cost fixture allowed unconstrained (six degree of freedom, 6 DOF) testing of fresh-frozen cadaveric lumbar spine. PMID- 26151290 TI - Targeting skeletal muscle mitochondria to prevent type 2 diabetes in youth. AB - The prevalence of type 2 diabetes (T2D) has increased dramatically over the past two decades, not only among adults but also among adolescents. T2D is a systemic disorder affecting every organ system and is especially damaging to the cardiovascular system, predisposing individuals to severe cardiac and vascular complications. The precise mechanisms that cause T2D are an area of active research. Most current theories suggest that the process begins with peripheral insulin resistance that precedes failure of the pancreatic beta-cells to secrete sufficient insulin to maintain normoglycemia. A growing body of literature has highlighted multiple aspects of mitochondrial function, including oxidative phosphorylation, lipid homeostasis, and mitochondrial quality control in the regulation of peripheral insulin sensitivity. Whether the cellular mechanisms of insulin resistance in adults are comparable to that in adolescents remains unclear. This review will summarize both clinical and basic studies that shed light on how alterations in skeletal muscle mitochondrial function contribute to whole body insulin resistance and will discuss the evidence supporting high intensity exercise training as a therapy to circumvent skeletal muscle mitochondrial dysfunction to restore insulin sensitivity in both adults and adolescents. PMID- 26151291 TI - In Situ Formed Acetal-Facilitated Synthesis of Substituted Indene Derivatives from o-Alkenylbenzaldehydes. AB - A new protocol has been developed for the synthesis of indene derivatives in a diastereoselective manner from o-alkenylbenzaldehydes and enolizable ketones in the presence of trimethyl orthoformate and catalytic triflic acid. This method involves tandem in situ formed acetal-assisted Claisen-Schmidt condensation followed by 5-exo-trig cyclization/Michael addition in one-pot. It has also been shown that the chalcones derived from o-alkenylbenzaldehydes and ketones can effectively be transformed into indene derivatives in the presence of TfOH catalyst alone. PMID- 26151292 TI - Mechanism and Dynamics of Intramolecular C-H Insertion Reactions of 1-Aza-2 azoniaallene Salts. AB - The 1-aza-2-azoniaallene salts, generated from alpha-chloroazo compounds by treatment with halophilic Lewis acids, undergo intramolecular C-H amination reactions to form pyrazolines in good to excellent yields. This intramolecular amination occurs readily at both benzylic and tertiary aliphatic positions and proceeds at an enantioenriched chiral center with retention of stereochemistry. Competition experiments show that insertion occurs more readily at an electron rich benzylic position than it does at an electron-deficient one. The C-H amination reaction occurs only with certain tethers connecting the heteroallene cation and the pendant aryl groups. With a longer tether or when the reaction is intermolecular, electrophilic aromatic substitution occurs instead of C-H amination. The mechanism and origins of stereospecificity and chemoselectivity were explored with density functional theory (B3LYP and M06-2X). The 1-aza-2 azoniaallene cation undergoes C-H amination through a hydride transfer transition state to form the N-H bond, and the subsequent C-N bond formation occurs spontaneously to generate the heterocyclic product. This concerted two-stage mechanism was shown by IRC and quasi-classical molecular dynamics trajectory studies. PMID- 26151293 TI - MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses. AB - Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhanced with strong adjuvants such as TLR ligands. However, often these adjuvants have off-target effects, and would benefit from a DC-specific targeting strategy, similar to the tumour antigen. The goal of this study was to develop a strategy for specifically targeting DC with tumour antigen and adjuvant by using glycoliposomes. We have generated liposomes containing the glycan Lewis(Le)(X) which is highly specific for the C-type lectin receptor DC-SIGN expressed by DC. Le(X)-modified liposomes were taken up by human monocyte-derived DC in a DC-SIGN-specific manner. As adjuvants we incorporated the TLR ligands Pam3CySK4, Poly I:C, MPLA and R848 into liposomes and compared their adjuvant capacity on DC. Incorporation of the TLR4 ligand MPLA into glycoliposomes induced DC maturation and production of pro inflammatory cytokines, in a DC-SIGN-specific manner, and DC activation was comparable to administration of soluble MPLA. Incorporation of MPLA into glycoliposomes significantly enhanced antigen cross-presentation of the melanoma tumour antigen gp100280-288 peptide to CD8(+) T cells compared to non glycosylated MPLA liposomes. Importantly, antigen cross-presentation of the gp100280-288 peptide was significantly higher using MPLA glycoliposomes compared to the co-administration of soluble MPLA with glycoliposomes. Taken together, our data demonstrates that specific targeting of a gp100 tumour antigen and the adjuvant MPLA to DC-SIGN-expressing DC enhances the uptake of peptide-containing liposomes, the activation of DC, and induces tumour antigen-specific CD8(+) T cell responses. These data demonstrate that adjuvant-containing glycoliposome based vaccines targeting DC-SIGN(+) DC represent a powerful new approach for CD8(+) T cell activation. PMID- 26151294 TI - Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved. AB - PURPOSE/AIM: Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. As yet, no specific treatment is available for HALI. The present study aims to investigate the effects of edaravone on hyperoxia-induced oxidative injury and the underlying mechanism. MATERIALS AND METHODS: We treated rats and human pulmonary alveolar epithelial cells with hyperoxia and different concentration of edaravone, then examined the effects of edaravone on cell viability, cell injury and two oxidative products. The roles of heme oxygenase-1 (HO-1) and PI3K/Akt pathway were explored using Western blot and corresponding inhibitors. RESULTS: The results showed that edaravone reduced lung biochemical alterations induced by hyperoxia and mortality of rats, dose-dependently alleviated cell mortality, cell injury, and peroxidation of cellular lipid and DNA oxidative damage. It upregulated cellular HO-1 expression and activity, which was reversed by PI3K/Akt pathway inhibition. The administration of zinc protoporphyrin-IX, a HO-1 inhibitor, and LY249002, a PI3K/Akt pathway inhibitor, abolished the protective effects of edaravone in cells. CONCLUSIONS: This study indicates that edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia induced injury and the antioxidant effect may be related to upregulation of HO-1, which is regulated by PI3K/Akt pathway. PMID- 26151295 TI - Girdin regulates the migration and invasion of glioma cells via the PI3K-Akt signaling pathway. AB - Girdin, an actin-binding protein, is associated with cell migration and is expressed at high levels in glioma cells. However, the association between girdin and the development of glioma remains to be elucidated. In the present study, short-hairpin RNA technology was used to silence the gene expression of girdin. The effects of girdin silencing on glioma cell proliferation, migration and invasion were then assessed using a cell viability assay, wound-healing assay, transwell invasion assay, reverse transcription-quantitative polymerase chain reaction, western blot analysis and gelatin zymography. The results suggested that girdin silencing inhibited the proliferation, migration and invasion of glioma cells. In addition, the expression levels and activity of matrix metalloproteinase (MMP)-2 and MMP-9 were also affected by girdin silencing. Further mechanistic investigation indicated that girdin may regulate glioma cell migration and invasion through the phosphatidylinositol-3-kinase/protein kinase B (PI3K-Akt) signaling pathway. Therefore, the results of the present study provide a theoretical foundation for the development of anticancer drugs. PMID- 26151298 TI - Reviews. PMID- 26151299 TI - You're the Flight Surgeon. AB - Howard CT, Vu P. You're the flight surgeon: hand, foot, and mouth disease. Aerosp Med Hum Perform. 2015; 86(5):497-500. PMID- 26151300 TI - You're the Flight Surgeon. AB - Woolford JS. You're the flight surgeon: epilepsy. Aerosp Med Hum Perform. 2015; 86(4):500-503. PMID- 26151301 TI - Atmospheric plume progression as a function of time and distance from the release point for radioactive isotopes. AB - The radionuclide network of the International Monitoring System comprises up to 80 stations around the world that have aerosol and xenon monitoring systems designed to detect releases of radioactive materials to the atmosphere from nuclear explosions. A rule of thumb description of plume concentration and duration versus time and distance from the release point is useful when designing and deploying new sample collection systems. This paper uses plume development from atmospheric transport modeling to provide a power-law rule describing atmospheric dilution factors as a function of distance from the release point. Consider the plume center-line concentration seen by a ground-level sampler as a function of time based on a short-duration ground-level release of a nondepositing radioactive tracer. The concentration C (Bq m(-3)) near the ground varies with distance from the source with the relationship C=R*A(D,C) *e ( lambda(-1.552+0.0405*D)) * 5.37*10(-8) * D(-2.35) where R is the release magnitude (Bq), D is the separation distance (km) from the ground level release to the measurement location, lambda is the decay constant (h(-1)) for the radionuclide of interest and AD,C is an attenuation factor that depends on the length of the sample collection period. This relationship is based on the median concentration for 10 release locations with different geographic characteristics and 365 days of releases at each location, and it has an R(2) of 0.99 for 32 distances from 100 to 3000 km. In addition, 90 percent of the modeled plumes fall within approximately one order of magnitude of this curve for all distances. PMID- 26151302 TI - Author reply to letter. PMID- 26151303 TI - Stromal-Derived Factor-1alpha and Interleukin-7 Treatment Improves Homeostatic Proliferation of Naive CD4(+) T Cells after Allogeneic Stem Cell Transplantation. AB - Graft-versus-host disease (GVHD) impairs immune reconstitution after allogeneic stem cell transplantation (allo-SCT) and effective therapies aimed at restoring T cell counts in GVHD patients have yet to be developed. During GVHD, CD4(+) T cell reconstitution is particularly affected and current models hold that GVHD insult to the peripheral lymphoid niche is responsible for this effect. Here, we show that naive CD4(+) T cell homeostatic proliferation (HP) is lost during GVHD because of low systemic IL-7 and impaired dendritic cell (DC) regeneration. We assessed factors involved in DC differentiation and found that although fms-like tyrosine kinase 3 ligand (Flt3-L) levels were normal, stromal-derived factor 1alpha (SDF-1alpha) was diminished in the blood of GVHD mice. Unlike Flt3-L treatment, the administration of SDF-1alpha specifically increased CD8alpha(+) DC numbers and did not worsen GVHD. Importantly, CD4(+) T cell HP was enhanced only when IL-7 and SDF-1alpha or Flt3L were coadministered, confirming the crucial role of DCs and IL-7 in restoring CD4(+) T cell regeneration during GVHD. Altogether, our results indicate that CD8alpha(+) DCs are part of the peripheral niche that controls CD4(+) T cell HP and that their depletion, combined with low systemic IL-7, explains how GVHD constrains naive CD4(+) T cell reconstitution after allo-SCT. PMID- 26151304 TI - Sensitive Replicate Real-Time Quantitative PCR of BCR-ABL Shows Deep Molecular Responses in Long-Term Post-Allogeneic Stem Cell Transplantation Chronic Myeloid Leukemia Patients. AB - Real-time quantitative PCR (RT-qPCR) is commonly used for follow-up of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors, but its current sensitivity does not allow detection of very low BCR-ABL levels. Therefore RT-qPCR negativity is not synonymous with complete molecular response. Replicate RT-qPCR had shown increased sensitivity in tyrosine kinase inhibitor treated patients and was, therefore, used here to evaluate whether RT-qPCR negative post-allogeneic stem cell transplantation (SCT) patients harbor detectable disease. Samples from 12 patients were tested at 2 time points using 82 replicates of BCR-ABL RT-qPCR. One patient (38 months after SCT) had detectable transcripts at baseline and none at the follow-up test, done at a median of 107 months after SCT. This suggests cure from CML in the majority of allogeneic SCT patients who have no transcripts detectable by replicate RT-qPCR for BCR-ABL. PMID- 26151306 TI - Susceptibility of Soil Bound Mercury to Gaseous Emission As a Function of Source Depth: An Enriched Isotope Tracer Investigation. AB - Soil mercury (Hg) emissions are an important component of the global Hg cycle. Sunlight induced photoreduction of oxidized Hg to gaseous elemental Hg is an important mechanism controlling emissions from the soil surface, however we currently understand little about how subsurface Hg stores participate in gaseous Hg cycling. Our study objective was to investigate the ability of Hg at deeper soil depths to participate in emissions. Soil fluxes were measured under controlled laboratory conditions utilizing an enriched stable Hg isotope tracer buried at 0, 1, 2, and 5 cm below the surface. Under dry and low-light conditions, the Hg isotope tracer buried at the different depths participated similarly in surface emissions (median flux: 7.5 ng m(-2) h(-1)). When the soils were wetted, Hg isotope tracer emissions increased significantly (up to 285 ng m( 2) h(-1)), with the highest fluxes (76% of emissions) originating from the surface 1 cm amended soils and decreasing with depth. Mercury associated with sandy soil up to 6 cm below the surface can be emitted, clearly demonstrating that volatilization can occur via processes unrelated to sunlight. These results have important implications for considering how long older, legacy soil Hg contamination continues to cycle between soil and atmosphere. PMID- 26151305 TI - Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis. AB - Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology. PMID- 26151307 TI - Involvement of prostaglandin I(2) in nitric oxide-induced vasodilation of retinal arterioles in rats. AB - The soluble guanylyl cyclase/cGMP system plays an important role in the vasodilator response to nitric oxide (NO) in various vascular beds. However, in rat retinal arterioles, the cyclooxygenase-1/cAMP-mediated pathway contributes to the vasodilator effects of NO, although the specific prostanoid involved remains to be elucidated. In the present study, we investigated the role of prostaglandin I2 and its receptor (prostanoid IP receptor) system in NO-induced vasodilation of rat retinal arterioles in vivo. Fundus images were captured using a digital camera that was equipped with a special objective lens. Changes in diameter of retinal arterioles were assessed. The NO donor (+/-)-(E)-4-ethyl-2-[(E) hydroxyimino]-5-nitro-3-hexenamide (NOR3) increased the diameter of retinal arterioles but decreased systemic blood pressure in a dose-dependent manner. Treatment of rats with indomethacin, a non-selective cyclooxygenase inhibitor, markedly attenuated the retinal vasodilator, but not depressor responses to NOR3. The prostanoid IP receptor antagonist 4,5-dihydro-N-[4-[[4-(1 methylethoxy)phenyl]methyl]phenyl]-1H-imadazol-2-amine (CAY10441), and the prostaglandin I2 synthase inhibitor 9alpha,11alpha-azoprosta-5Z,13E-dien-1-oic acid (U-51605), both showed similar preventive effects against the NOR3-induced retinal vasodilator response. Neither CAY10441 nor U-51605 showed any significant effects on the depressor response to NOR3. NOR3 enhanced the release of prostaglandin I2 from cultured human retinal microvascular endothelial cells and the NOR3-induced prostaglandin I2 release was almost completely abolished by the cyclooxygenase-1 inhibitor SC-560, but not by the cyclooxygenase-2 inhibitor NS 398. However, NOR3 did not increase the release of prostaglandin I2 from human intestinal microvascular endothelial cells. These results suggest that NO exerts its dilatory effect via cyclooxygenase-1/prostaglandin I2/prostanoid IP receptor signaling mechanisms in the retinal vasculature. PMID- 26151308 TI - Hypertonicity contributes to seawater aspiration-induced lung injury: Role of hypoxia-inducible factor 1alpha. AB - Drowning is an important public health problem, but the mechanism of acute lung injury induced by near-drowning is rarely reported. The aim of this study is to investigate the role of hypertonicity and HIF-1alpha in seawater aspiration induced lung injury. Diverse solutions were used to study the effect of hypertonicity on hypoxia, inflammation, vascular leakage, edema, and HIF-1alpha expression in lungs of rats. The relationship between hypertonicity and hypoxia, when they induced HIF-1alpha, was studied and the roles of ATM, PI3K, and p38 in the course of hypertonicity inducing HIF-1alpha were investigated. At last, our conclusion was verified with HIF-1alpha inhibitor and inducer in seawater aspiration rats. The results showed that hypertonicity, but not isotonicity and hypotonicity, promoted hypoxia, inflammation, vascular leakage, edema, and HIF 1alpha expression in lungs. Hypertonicity not only induced HIF-1alpha in a time- and dose-dependent manner but also could increase HIF-1alpha synergistically with hypoxia in AEC. Furthermore, hypertonicity increased HIF-1alpha by promoting its mRNA expression through both ATM and PI3K activation and by suppressing its protein degradation through p38 activation. During hyperosmotic stress, the increased HIF-1alpha promoted the production of the inflammatory cytokines in NR8383 and elevated monolayer permeability through increasing VEGF in RLMVEC. In conclusion, hypertonicity induced by aspirated seawater aggravated lung injury through increasing HIF-1alpha which promoted inflammation and edema in lung tissues in rats. PMID- 26151310 TI - Umbilical cord-derived mesenchymal stem cells promote proliferation and migration in MCF-7 and MDA-MB-231 breast cancer cells through activation of the ERK pathway. AB - Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues and to play an important role in cancer progression. However, the effects of MSCs on tumor progression remain controversial. The purpose of the present study was to detect the effects of human umbilical cord-derived MSCs (hUC-MSCs) on the human breast cancer cell lines MDA-MB-231 and MCF-7 in vitro and the underlying mechanisms. MSCs were isolated and identified from umbilical cord tissues. MDA-MB-231 and MCF 7 cells were treated with conditioned medium (CM) from 10 and 20% umbilical cord MSCs (UC-MSCs), and the resulting changes in proliferation and migration were investigated. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and plate clone formation assays were used to assess the effect on proliferation, and the effects of CM on MDA-MB-231 and MCF-7 migration were assessed through scratch wound and Transwell migration assays. The expression of cell proliferation- and metastasis-related genes and proteins and activation of the ERK signaling pathway were analyzed by RT-PCR and western blot assays. UC MSCs are characteristically similar to bone marrow MSCs (BM-MSCs) and exhibit multipotential differentiation capability (i.e., osteoblasts and adipocytes). The MTT, plate clone formation, scratch wound and Transwell migration assay results revealed that 10 and 20% CM promoted the proliferation and migration to higher levels than those observed in the control group. Our findings showed that UC-MSC CM inhibited E-cadherin expression, increased the expression of N-cadherin and proliferating cell nuclear antigen (PCNA) and enhanced the expression of ZEB1, a transcription factor involved in epithelial-to-mesenchymal transition (EMT), through activation of the ERK pathway. U0126, an inhibitor of ERK, reversed the effects of UC-MSC-CM on breast cancer cell proliferation and migration. We conclude that UC-MSCs promote the proliferation and migration of breast cancer cell lines via activation of the ERK pathway. PMID- 26151309 TI - Tackling tuberculosis: Insights from an international TB Summit in London. AB - Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience. PMID- 26151311 TI - An ontology for Autism Spectrum Disorder (ASD) to infer ASD phenotypes from Autism Diagnostic Interview-Revised data. AB - OBJECTIVE: Our goal is to create an ontology that will allow data integration and reasoning with subject data to classify subjects, and based on this classification, to infer new knowledge on Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders (NDD). We take a first step toward this goal by extending an existing autism ontology to allow automatic inference of ASD phenotypes and Diagnostic & Statistical Manual of Mental Disorders (DSM) criteria based on subjects' Autism Diagnostic Interview-Revised (ADI-R) assessment data. MATERIALS AND METHODS: Knowledge regarding diagnostic instruments, ASD phenotypes and risk factors was added to augment an existing autism ontology via Ontology Web Language class definitions and semantic web rules. We developed a custom Protege plugin for enumerating combinatorial OWL axioms to support the many-to many relations of ADI-R items to diagnostic categories in the DSM. We utilized a reasoner to infer whether 2642 subjects, whose data was obtained from the Simons Foundation Autism Research Initiative, meet DSM-IV-TR (DSM-IV) and DSM-5 diagnostic criteria based on their ADI-R data. RESULTS: We extended the ontology by adding 443 classes and 632 rules that represent phenotypes, along with their synonyms, environmental risk factors, and frequency of comorbidities. Applying the rules on the data set showed that the method produced accurate results: the true positive and true negative rates for inferring autistic disorder diagnosis according to DSM-IV criteria were 1 and 0.065, respectively; the true positive rate for inferring ASD based on DSM-5 criteria was 0.94. DISCUSSION: The ontology allows automatic inference of subjects' disease phenotypes and diagnosis with high accuracy. CONCLUSION: The ontology may benefit future studies by serving as a knowledge base for ASD. In addition, by adding knowledge of related NDDs, commonalities and differences in manifestations and risk factors could be automatically inferred, contributing to the understanding of ASD pathophysiology. PMID- 26151312 TI - PhenoPredict: A disease phenome-wide drug repositioning approach towards schizophrenia drug discovery. AB - Schizophrenia (SCZ) is a common complex disorder with poorly understood mechanisms and no effective drug treatments. Despite the high prevalence and vast unmet medical need represented by the disease, many drug companies have moved away from the development of drugs for SCZ. Therefore, alternative strategies are needed for the discovery of truly innovative drug treatments for SCZ. Here, we present a disease phenome-driven computational drug repositioning approach for SCZ. We developed a novel drug repositioning system, PhenoPredict, by inferring drug treatments for SCZ from diseases that are phenotypically related to SCZ. The key to PhenoPredict is the availability of a comprehensive drug treatment knowledge base that we recently constructed. PhenoPredict retrieved all 18 FDA approved SCZ drugs and ranked them highly (recall=1.0, and average ranking of 8.49%). When compared to PREDICT, one of the most comprehensive drug repositioning systems currently available, in novel predictions, PhenoPredict represented clear improvements over PREDICT in Precision-Recall (PR) curves, with a significant 98.8% improvement in the area under curve (AUC) of the PR curves. In addition, we discovered many drug candidates with mechanisms of action fundamentally different from traditional antipsychotics, some of which had published literature evidence indicating their treatment benefits in SCZ patients. In summary, although the fundamental pathophysiological mechanisms of SCZ remain unknown, integrated systems approaches to studying phenotypic connections among diseases may facilitate the discovery of innovative SCZ drugs. PMID- 26151313 TI - Critical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma. AB - Little is known on the control of lymphomas by NK cells. Here, we study the role of the NK group 2D (NKG2D) receptor for the immunosurveillance of lymphoma. By using transplantable tumors as well as a lambda-myc-transgenic model of endogenously arising lymphoma and NKG2D-deficient mice, we show that NK cells eliminate tumor cells in vivo after receiving two signals. One step involved the activation of NK cells giving rise to IFN-gamma expression, which was effected by MHCI(low) tumor cells or DCs. However, this was necessary but not sufficient to mediate cytotoxicity. Triggering cytotoxicity additionally required a second step, which could be mediated by engagement of the NKG2D receptor. Thus, NKG2D deficient NK cells could become activated in vivo, but they were not able to reject transplanted lymphomas or to degranulate in animals bearing autochthonous lymphomas. Tumor growth in NKG2D-deficient lambda-myc-transgenic mice was significantly accelerated compared to NKG2D-competent animals. Whereas the latter developed tumors that lost expression of NKG2D ligands (NKG2D-L) in late disease stages, this did not occur in NKG2D-deficient mice. This indicates that NK cells and the NKG2D receptor play a role for control of lymphomas and that selection for NKG2D-L loss mutants provides a mechanism of tumor escape. PMID- 26151314 TI - Using soil properties to predict in vivo bioavailability of lead in soils. AB - Soil plays a significant role in controlling the potential bioavailability of contaminants in the environment. In this study, eleven soils were used to investigate the relationship between soil properties and relative bioavailability (RB) of lead (Pb). To minimise the effect of source of Pb on in vivo bioavailability, uncontaminated study soils were spiked with 1500 mg Pb/kg soil and aged for 10-12 months prior to investigating the relationships between soil properties and in vivo RB of Pb using swine model. The biological responses to oral administration of Pb in aqueous phase or as spiked soils were compared by applying a two-compartment pharmacokinetic model to blood Pb concentration. The study revealed that RB of Pb from aged soils ranged from 30+/-9% to 83+/-7%. The very different RB of Pb in these soils was attributed to variations in the soils' physico-chemical properties. This was established using sorption studies showing: firstly, Freundlich partition coefficients that ranged from 21 to 234; and secondly, a strongly significant (R(2)=0.94, P<0.001) exponential relationship between RB and Freundlich partition coefficient (Kd). This simple exponential model can be used to predict relative bioavailability of Pb in contaminated soils. To the best of our knowledge, this is the first such model derived using sorption partition coefficient to predict the relative bioavailability of Pb. PMID- 26151315 TI - An Evaluation of the My ParticipACTION Campaign to Increase Self-Efficacy for Being More Physically Active. AB - The objective of the My ParticipACTION campaign was to inspire Canadian adults to increase their physical activity through messaging that was relevant, engaging, and designed to build self-efficacy to be more active. This research examined the communication effects of the campaign according to the a priori Hierarchy of Effects Model (saliency -> cognitive engagement -> self-efficacy to become more active -> trial behavior) and investigated how these effects related to overall self-efficacy for physical activity, intention to be active, and current activity level. Participants (N = 1,110) were recruited from an existing panel of Canadian adults 18 years and older and completed a short online questionnaire about the potential communication effects. Logistic regression models were constructed to test the communication effects adjusting for age, gender, and education. The relations were consistent with those hypothesized in the model. In addition, some earlier outcomes in the sequence of effects were associated with other outcomes further down the progression. When intention to be active was included, the initial relation between ad-specific self-efficacy and current physical activity disappeared. This analysis suggested that the campaign was successful in increasing self-efficacy to be more active and that using the Hierarchy of Effects Model was useful in guiding the design of campaign messages and assessing communication effects. Given the limited amount of theoretical testing of the Hierarchy of Effects Model, future research employing longitudinal designs is required to further confirm the communication effects of such an intervention and further test the model. PMID- 26151316 TI - Construction of Cu3Mo2O9 nanoplates with excellent lithium storage properties based on a pH-dependent dimensional change. AB - One-, two- and three-dimensional nanostructures of copper molybdenum oxide hydroxide were successfully constructed by a simple approach through a pH dependent dimensional transformation of ammonium copper molybdate. Thin nanoplates of copper molybdate, which were obtained by sintering the two dimensional nanobelts of copper molybdenum oxide hydroxide, exhibited remarkably high reversible lithium storage capacity, good rate capability and excellent cycling stability. PMID- 26151318 TI - Giant anisotropic magnetoresistance in a quantum anomalous Hall insulator. AB - When a three-dimensional ferromagnetic topological insulator thin film is magnetized out-of-plane, conduction ideally occurs through dissipationless, one dimensional (1D) chiral states that are characterized by a quantized, zero-field Hall conductance. The recent realization of this phenomenon, the quantum anomalous Hall effect, provides a conceptually new platform for studies of 1D transport, distinct from the traditionally studied quantum Hall effects that arise from Landau level formation. An important question arises in this context: how do these 1D edge states evolve as the magnetization is changed from out-of plane to in-plane? We examine this question by studying the field-tilt-driven crossover from predominantly edge-state transport to diffusive transport in Crx(Bi,Sb)(2-x)Te3 thin films. This crossover manifests itself in a giant, electrically tunable anisotropic magnetoresistance that we explain by employing a Landauer-Buttiker formalism. Our methodology provides a powerful means of quantifying dissipative effects in temperature and chemical potential regimes far from perfect quantization. PMID- 26151317 TI - Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. AB - Up to 80% of human cancers, in particular solid tumors, contain cells with abnormal chromosomal numbers, or aneuploidy, which is often linked with marked chromosomal instability. Whereas in some tumors the aneuploidy occurs by missegregation of one or a few chromosomes, aneuploidy can also arise during proliferation of inherently unstable tetraploid cells generated by whole genome doubling from diploid cells. Recent findings from cancer genome sequencing projects suggest that nearly 40% of tumors underwent whole genome doubling at some point of tumorigenesis, yet its contribution to cancer phenotypes and benefits for malignant growth remain unclear. Here, we investigated the consequences of a whole genome doubling in both cancerous and non-transformed p53 positive human cells. SNP array analysis and multicolor karyotyping revealed that induced whole-genome doubling led to variable aneuploidy. We found that chromosomal instability (CIN) is a frequent, but not a default outcome of whole genome doubling. The CIN phenotypes were accompanied by increased tolerance to mitotic errors that was mediated by suppression of the p53 signaling. Additionally, the expression of pro-apoptotic factors, such as iASPP and cIAP2, was downregulated. Furthermore, we found that whole genome doubling promotes resistance to a broad spectrum of chemotherapeutic drugs and stimulates anchorage independent growth even in non-transformed p53-positive human cells. Taken together, whole genome doubling provides multifaceted benefits for malignant growth. Our findings provide new insight why genome-doubling promotes tumorigenesis and correlates with poor survival in cancer. PMID- 26151320 TI - All aboard: Will molecular tumor boards help cancer patients? PMID- 26151319 TI - Structure-Activity Relationship Studies of Substituted 2-(Isoxazol-3-yl)-2-oxo-N' phenyl-acetohydrazonoyl Cyanide Analogues: Identification of Potent Exchange Proteins Directly Activated by cAMP (EPAC) Antagonists. AB - Exchange proteins directly activated by cAMP (EPAC) as guanine nucleotide exchange factors mediate the effects of the pivotal second messenger cAMP, thereby regulating a wide variety of intracellular physiological and pathophysiological processes. A series of novel 2-(isoxazol-3-yl)-2-oxo-N'-phenyl acetohydrazonoyl cyanide EPAC antagonists was synthesized and evaluated in an effort to optimize properties of the previously identified high-throughput (HTS) hit 1 (ESI-09). Structure-activity relationship (SAR) analysis led to the discovery of several more active EPAC antagonists (e.g., 22 (HJC0726), 35 (NY0123), and 47 (NY0173)) with low micromolar inhibitory activity. These inhibitors may serve as valuable pharmacological probes to facilitate our efforts in elucidating the biological functions of EPAC and developing potential novel therapeutics against human diseases. Our SAR results have also revealed that further modification at the 3-, 4-, and 5-positions of the phenyl ring as well as the 5-position of the isoxazole moiety may allow for the development of more potent EPAC antagonists. PMID- 26151321 TI - Almighty antibodies? A new wave of antibody-based approaches aims to combat HIV. PMID- 26151323 TI - To build better tuberculosis diagnostics, look for 'biosignatures'. PMID- 26151324 TI - Liquid biopsies reveal the dynamic nature of resistance mechanisms in solid tumors. PMID- 26151325 TI - Shifts in macrophage cytokine production drive muscle fibrosis. PMID- 26151326 TI - Tracing human brown fat. PMID- 26151327 TI - Big data meets mechanism. AB - Inflammatory disease research is burgeoning. Large data sets are being generated to characterize the human immune response, while detailed mechanistic studies are defining the role of specific cell types and sensors in inflammatory disease. Future efforts are needed to integrate these approaches and guide precision medicine. PMID- 26151328 TI - Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. PMID- 26151329 TI - Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. PMID- 26151330 TI - Jordan's principle and Indigenous children with disabilities in Canada: jurisdiction, advocacy, and research. AB - This article discusses Indigenous (1) (1)In this article, the terms Indigenous, First Nations, Aboriginal, and Treaty Indian are used interchangeably, and as needed to describe the political reality of the First Peoples of Canada. children with disabilities in Canada and examines their experiences with federal and provincial jurisdictional and funding disputes. It explores Canada's adversarial legal and policy techniques to delay implementation and funding of Jordan's Principle, a Canadian Human Rights Tribunal action seeking to address the delays, and the recommendations of a recent independent Canadian research project. Finally, it suggests ways to advance Jordan's Principle in Canada and elsewhere. PMID- 26151331 TI - Growth Mechanism and Electrical and Magnetic Properties of Ag-Fe3O4 Core-Shell Nanowires. AB - One-dimensional Ag-Fe3O4 core-shell heteronanowires have been synthesized by a facile and effective coprecipitation method, in which silver nanowires (AgNWs) were used as the nucleation site for growth of Fe3O4 in aqueous solution. The size and morphology control of the core-shell nanowires were achieved by simple adjustments of reaction conditions including FeCl3/FeCl2 concentration, poly(vinylpyrrolidone) (PVP) concentration, reaction temperature, and time. It was found that the Fe3O4 shell thickness could be tuned from 6 to 76 nm with the morphology variation between nanopheres and nanorods. A possible growth mechanism of Ag-Fe3O4 core-shell nanowires was proposed. First, the C?O derived from PVP on the surface of AgNWs provided nucleation points and in situ oxidation reaction between AgNWs and FeCl3/FeCl2 solution promoted the accumulation of Fe(3+) and Fe(2+) on the AgNWs surface. Second, Fe3O4 nanoparticles nucleated on the AgNWs surface. Lastly, Fe3O4 nanoparticles grew on the AgNWs surface by using up the reagents. Higher FeCl3/FeCl2 concentration or higher temperature led to faster nucleation and growth, resulting in the formation of Fe3O4 nanorods, whereas lower concentration or lower temperature resulted in slower nucleation and growth, leading to the formation of Fe3O4 nanospheres. Furthermore, the Ag-Fe3O4 core-shell nanowires exhibited good electrical properties and ferromagnetic properties at room temperature. Particularly, the magnetic saturation values (Ms) increased from 5.7 to 26.4 emu g(-1) with increasing Fe3O4 shell thickness from 9 to 76 nm. This growth of magnetic nanoparticles on 1D metal nanowires is meaningful from both fundamental and applied perspectives. PMID- 26151332 TI - BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase. AB - Polycomb repressive complex 1 (PRC1) is required for ubiquitination of histone H2A lysine 119, an epigenetic mark associated with repression of genes important in developmental regulation. The E3 ligase activity of PRC1 resides in the RING1A/B subunit when paired with one of six PCGF partners. The best known of these is the oncogene BMI1/PCGF4. We find that canonical PRC1 E3 ligases such as PCGF4-RING1B have intrinsically very low enzymatic activity compared with non canonical PRC1 RING dimers. The structure of a high-activity variant in complex with E2 (PCGF5-RING1B-UbcH5c) reveals only subtle differences from an earlier PCGF4 complex structure. However, two charged residues present in the modelled interface with E2-conjugated ubiquitin prove critical: in BMI1/PCGF4, these residues form a salt bridge that may limit efficient ubiquitin transfer. The intrinsically low activity of the PCGF4-RING1B heterodimer is offset by a relatively favourable interaction with nucleosome substrates, resulting in an efficient site-specific monoubiquitination. PMID- 26151333 TI - eZinCh-2: A Versatile, Genetically Encoded FRET Sensor for Cytosolic and Intraorganelle Zn(2+) Imaging. AB - Zn(2+) plays essential and diverse roles in numerous cellular processes. To get a better understanding of intracellular Zn(2+) homeostasis and the putative signaling role of Zn(2+), various fluorescent sensors have been developed that allow monitoring of Zn(2+) concentrations in single living cells in real time. Thus far, two families of genetically encoded FRET-based Zn(2+) sensors have been most widely applied, the eCALWY sensors developed by our group and the ZapCY sensors developed by Palmer and co-workers. Both have been successfully used to measure cytosolic free Zn(2+), but distinctly different concentrations have been reported when using these sensors to measure Zn(2+) concentrations in the ER and mitochondria. Here, we report the development of a versatile alternative FRET sensor containing a de novo Cys2His2 binding pocket that was created on the surface of the donor and acceptor fluorescent domains. This eZinCh-2 sensor binds Zn(2+) with a high affinity that is similar to that of eCALWY-4 (Kd = 1 nM at pH 7.1), while displaying a substantially larger change in emission ratio. eZinCh-2 not only provides an attractive alternative for measuring Zn(2+) in the cytosol but was also successfully used for measuring Zn(2+) in the ER, mitochondria, and secretory vesicles. Moreover, organelle-targeted eZinCh-2 can also be used in combination with the previously reported redCALWY sensors to allow multicolor imaging of intracellular Zn(2+) simultaneously in the cytosol and the ER or mitochondria. PMID- 26151334 TI - Thyrospheres From Normal or Malignant Thyroid Tissue Have Different Biological, Functional, and Genetic Features. AB - CONTEXT: Cancer stem cells from several human malignancies, including poorly differentiated thyroid carcinoma and thyroid cancer cell lines, have been cultured in vitro as sphere-forming cells. These thyroid cancer stem cells were proven to be able to reproduce the original tumor in a xenograft orthotopic model. OBJECTIVES: The objective of the study was to characterize papillary thyroid carcinoma (PTC) spheres from well-differentiated thyroid cancer and normal thyroid (NT) spheres obtained from the contralateral thyroid tissue of the same patient. DESIGN: Thyrospheres from PTCs and NTs were isolated. MAIN OUTCOME MEASURES: Gene expression analysis by real-time PCR, immunofluorescence studies, and fluorescence-activated cell sorter analysis in thyrospheres from PTCs and NTs have been evaluated. CONCLUSIONS: Compared with NT spheres, PTC spheres are larger, more irregular, and more clonogenic and have a higher rate of symmetric division. Moreover, PTC spheres express higher levels of stem cell markers and lower levels of thyroid-specific genes compared with NT spheres. Under appropriate conditions, NT spheres differentiated into thyrocytes, whereas PTC spheres did not, displaying a defect in the differentiation potential. Immunofluorescence experiments indicated that, in NT spheres, progenitor cells are mainly present in the sphere core, and the sphere periphery contains thyroid precursor cells already committed to differentiation. PTC spheres are not polarized like NT spheres. Unlike cells differentiated from NT spheres, TSH did not significantly stimulate cAMP production in cells differentiated from PTC spheres. A microarray analysis performed in paired samples (NT and PTC spheres from the same patient) indicated that NT and PTC spheres display a gene expression pattern typical of stem/progenitor cells; however, compared with NT spheres, PTC spheres display a unique gene expression pattern that might be involved in PTC progression. PMID- 26151336 TI - Postprandial Endotoxemia Linked With Chylomicrons and Lipopolysaccharides Handling in Obese Versus Lean Men: A Lipid Dose-Effect Trial. AB - CONTEXT: Postprandial endotoxemia is a metabolic risk factor, which has been shown to originate from the intestinal absorption of gut lipopolysaccharides (LPS) using nonphysiological high-fat tests. OBJECTIVE: This study aimed to determine whether different realistic fat amounts can modulate postprandial dynamics and handling of LPS by varying postprandial lipidemia in humans of different body mass indices. DESIGN, SETTING, AND PARTICIPANTS: In a randomized, controlled, cross-over study in nutrition research center, eight normal-weight (NW) and eight obese age-matched men, without diabetes nor dyslipidemia, ingested breakfasts containing 10 vs 40 g fat. Blood samples, leukocytes, and chylomicron rich fractions were obtained during 8 h. Plasma and chylomicron-endotoxemia, plasma LPS transporters (LBP, sCD14) and IL-6, nuclear factor kappaB (NF-kappaB) translocation, and IL-6 gene expression of immune cells were measured. MAIN OUTCOME: The postprandial fatty acid handling after ingesting 40 g fat was previously published as primary outcome. The secondary outcomes were inflammatory ones including postprandial endotoxemia, LPS handling, and plasma markers of inflammation after ingesting 10 or 40 g fat. RESULTS: Chylomicronemia increased in all subjects according to ingested fat amount (P < .01), but only obese had higher postprandial endotoxemia after 40 g (P < .05). Obese subject chylomicrons were more enriched with LPS compared with NW (PBMI < .01). We observed neither NF kappaB translocation, nor variation of IL-6 expression in leukocytes. In both groups, fat amount did not modify postprandial response of plasma IL-6. However, the area under the curve (AUC) of IL-6 in obese was higher than in NW (P < .05) parallel to higher fasting LPS-binding protein (LBP; P < .05). AUC of IL-6 was correlated with LBP (P < .01). CONCLUSION: Postprandial endotoxemia is modulated by ingested fat amount in obese men. LPS handling in plasma through chylomicrons and LBP seems critical in driving the acute inflammatory response. The pathophysiological importance of repeated postprandial endotoxemia excursions and their contribution to a vicious cycle of LBP-driven low-grade inflammation deserve further investigation in the nutritional management of cardio-metabolic risk prevention. PMID- 26151335 TI - Subclinical Vascular Dysfunction Associated with Metabolic Syndrome in African Americans and Whites. AB - CONTEXT: The diagnosis of metabolic syndrome (MetS) identifies individuals at risk for developing diabetes and cardiovascular disease. African Americans (AAs) have high rates of cardiovascular disease and subclinical vascular disease including arterial stiffness and microvascular dysfunction but have relatively low rates of MetS. OBJECTIVE: The objective of the study was to evaluate the relationship between MetS and vascular function in a biracial cohort with the hypothesis that the diagnosis of MetS underestimates subclinical vascular disease in AAs. DESIGN: We measured components of MetS in a community-based cohort of 951 AAs and white subjects (aged 48.8 +/- 11 y, 47% AA, 55% female). MAIN OUTCOME MEASURES: Using digital pulse amplitude tonometry, we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function. Using applanation tonometry (Sphygmocor), central augmentation index (CAIx) and pulse wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively. RESULTS: MetS was present in 24.0% of subjects and was associated with increased PWV (P < .001) and CAIx (P < .001) and a trend to lower RHI (P = .068) in both races. However, in subjects without MetS, AAs had lower RHI (P < .001) and higher PWV (P = .003) and CAIx (P = .002) compared with white subjects. Addition of an extra MetS criterion point for AAs with hypertension eliminated the racial differences in PWV and CAIx but not RHI. CONCLUSION: Although MetS is associated with microvascular dysfunction and increased arterial stiffness in both racial groups, AAs without MetS have greater vascular dysfunction compared with whites. Additional weighting for hypertension in AAs attenuated the racial differences in subclinical disease associated with MetS. PMID- 26151337 TI - Relative Influence of Trans-Pacific and Regional Atmospheric Transport of PAHs in the Pacific Northwest, U.S. AB - The relative influences of trans-Pacific and regional atmospheric transport on measured concentrations of polycyclic aromatic hydrocarbons (PAHs), PAH derivatives (nitro- (NPAH) and oxy-(OPAH)), organic carbon (OC), and particulate matter (PM) less than 2.5 MUm in diameter (PM2.5) were investigated in the Pacific Northwest, U.S. in 2010-2011. Ambient high volume PM2.5 air samples were collected at two sites in the Pacific Northwest: (1.) Mount Bachelor Observatory (MBO) in the Oregon Cascade Range (2763 m above sea level (asl)) and 2.) Confederated Tribes of the Umatilla Indian Reservation (CTUIR) in the Columbia River Gorge (CRG) (954 m asl). At MBO, the 1,8-dinitropyrene concentration was significantly positively correlated with the time a sampled air mass spent over Asia, suggesting that this NPAH may be a good marker for trans-Pacific atmospheric transport. At CTUIR, NOx, CO2, and SO2 emissions from a 585 MW coal fired power plant, in Boardman OR, were found to be significantly positively correlated with PAH, OPAH, NPAH, OC, and PM2.5 concentrations. By comparing the Boardman Plant operational time frames when the plant was operating to when it was shut down, the plant was found to contribute a large percentage of the measured PAH (67%), NPAH (91%), OPAH (54%), PM2.5 (39%), and OC (38%) concentrations at CTUIR and the CRG prior to Spring 2011 and likely masked trans Pacific atmospheric transport events to the CRG. Upgrades installed to the Boardman Plant in the spring of 2011 dramatically reduced the plant's contribution to PAH and OPAH concentrations (by ~72% and ~40%, respectively) at CTUIR and the CRG, but not NPAH, PM2.5 or OC concentrations. PMID- 26151338 TI - Pathogenesis of glucocorticoid-induced avascular necrosis: A microarray analysis of gene expression in vitro. AB - Avascular necrosis of the femoral head (ANFH) occurs following exposure to corticosteroids, and the proliferative capacity of the mesenchymal stem cells (MSCs) belonging to ANFH was reduced. The previous studies indicate that microRNA (miRNA) has an important regulatory role during proliferation and osteogenic differentiation of MSCs. Therefore, MSCs were obtained from healthy adults, and were cultured and osteogenically-induced by different dexamethasone concentrations. The proliferation and osteogenic differentiation capacities were examined through observing cellular morphology, alkaline phosphatase and alizarin red; miRNA expression was investigated using an miRNA gene chip and miRNA of differential expressions were retrieved through a database to analyze its regulatory effect. Dexamethasone at a concentration of 10(-7) mol/l induced the proliferation and osteogenic differentiation of MSCs and resulted in evident miRNA expression profile changes. In total, 11 miRNAs were upregulated at 10(-7) mol/l while 6 were downregulated, and partial miRNA was identified to participate in the regulation of cell proliferation and cell apoptosis, MSC osteogenic differentiation, lipid metabolism and other processes. PMID- 26151339 TI - Differential expression, distinct localization and opposite effect on Golgi structure and cell differentiation by a novel splice variant of human PRMT5. AB - Alternative splicing contributes greatly to the proteomic diversity of metazoans. Protein arginine methyltransferase 5 (PRMT5) methylates arginines of Golgi components and other factors exerting diverse effects on cell growth/differentiation, but the underlying molecular basis for its subcellular distribution and diverse roles has not been fully understood. Here we show the detailed properties of an evolutionarily emerged splice variant of human PRMT5 (PRMT5S) that is distinct from the original isoform (PRMT5L). The isoforms are differentially expressed among mammalian cells and tissues. The PRMT5S is distributed all over the cell but PRMT5L mainly colocalizes with Giantin, a Golgi marker. PRMT5 knockdown led to an enlarged Giantin pattern, which was prevented by the expression of either isoform. Rescuing PRMT5S also increased the percentage of cells with an interphase Giantin pattern compacted at one end of the nucleus, consistent with its cell cycle-arresting effect, while rescuing PRMT5L increased that of the mitotic Giantin patterns of dynamically fragmented structures. Moreover, the isoforms are differentially expressed during neuronal or dendritic cell differentiation, and their ectopic expression showed an opposite effect on dendritic cell differentiation. Furthermore, besides their differential regulation of gene expression, both isoforms also similarly regulate over a thousand genes particularly those involved in apoptosis and differentiation. Taking these properties together, we propose that their differential expression and subcellular localization contribute to spatial and temporal regulation of arginine methylation and gene expression to exert different effects. The novel PRMT5S likely contributes to the observed diverse effects of PRMT5 in cells. PMID- 26151340 TI - Inelastic mechanics: A unifying principle in biomechanics. AB - Many soft materials are classified as viscoelastic. They behave mechanically neither quite fluid-like nor quite solid-like - rather a bit of both. Biomaterials are often said to fall into this class. Here, we argue that this misses a crucial aspect, and that biomechanics is essentially damage mechanics, at heart. When deforming an animal cell or tissue, one can hardly avoid inducing the unfolding of protein domains, the unbinding of cytoskeletal crosslinkers, the breaking of weak sacrificial bonds, and the disruption of transient adhesions. We classify these activated structural changes as inelastic. They are often to a large degree reversible and are therefore not plastic in the proper sense, but they dissipate substantial amounts of elastic energy by structural damping. We review recent experiments involving biological materials on all scales, from single biopolymers over cells to model tissues, to illustrate the unifying power of this paradigm. A deliberately minimalistic yet phenomenologically very rich mathematical modeling framework for inelastic biomechanics is proposed. It transcends the conventional viscoelastic paradigm and suggests itself as a promising candidate for a unified description and interpretation of a wide range of experimental data. This article is part of a Special Issue entitled: Mechanobiology. PMID- 26151341 TI - Graphene growth and properties on metal substrates. AB - Graphene-metal interface as one of the interesting graphene-based objects attracts much attention from both application and fundamental science points of view. This paper gives a timely review of the recent experimental works on the growth and the electronic properties of the graphene-metal interfaces. This work makes a link between huge amount of experimental and theoretical data allowing one to understand the influence of the metallic substrate on the electronic properties of a graphene overlayer and how its properties can be modified in a controllable way. The further directions of studies and applications of the graphene-metal interfaces are discussed. PMID- 26151342 TI - Melatonin membrane receptor (MT1R) expression and nitro-oxidative stress in testis of golden hamster, Mesocricetus auratus: An age-dependent study. AB - Age-dependent decline in melatonin level induces nitro-oxidative stress that compromises physiological homeostasis including reproduction. However, less information exist regarding the age-dependent variation in local melatonin (lMel) concentration and MT1R expression in testis and its interaction with testicular steroidogenesis and nitro-oxidative stress in golden hamster, Mesocricetus auratus. Therefore, we evaluated lMel level along with MT1R expression and its possible interaction with steroidogenesis and nitro-oxidative stress in testes of young (6weeks), adult (15weeks) and old (2years) aged hamsters. Further, we injected the old hamsters with melatonin to address whether age-related decline in lMel and MT1R is responsible for the reduction in testicular steroidogenesis and antioxidant status. Increased expression of steroidogenic markers suggests increased testicular steroidogenesis in adult hamsters that declined in old hamsters. An age-dependent elevation in the level of NOX, TBARS, corticosterone and the expression of iNOS and GR with a concomitant decrease in enzyme activities for SOD, CAT, GSH-PX indicate increased nitro-oxidative stress in testes. Data suggest that reproductive senescence in male hamsters might be a consequence of declined lMel concentration with MT1R expression inducing nitro oxidative stress resulting in diminished testicular steroidogenesis. However, administration of Mel in old-aged hamsters significantly increased steroidogenesis and antioxidant status without a significant variation in lMel concentration and MT1R expression in testes. Therefore, decreased lMel and MT1R might not be the causative factor underlying the age-associated decrease in antioxidant defence and steroidogenesis in testes. In conclusion, Mel induced amelioration of testicular oxidative insult and elevation of steroidogenic activity suggests a potential role of increased nitro-oxidative stress underlying the age-dependent decrease in steroidogenesis. PMID- 26151343 TI - Quadrigeminal perimesencephalic subarachnoid hemorrhage. AB - OBJECTIVE: A variant of perimesencephalic subarachnoid hemorrhage (PSAH) has been described characterized by blood centered in the quadrigeminal cistern and limited to the superior vermian and perimesencephalic cisterns. Herein, three cases of quadrigeminal PSAH are presented. MATERIALS AND METHODS: Medical records of all patients who underwent digital subtraction angiography for evaluation of non-traumatic SAH between July 2002 and April 2012 were reviewed. Patients with anterior circulation aneurysms were excluded. Two blinded reviewers identified admission noncontrast CT scans with pretruncal and quadrigeminal patterns of PSAH. RESULTS: The total cohort included 106 patients: 53% (56/106) with one or more negative digital subtraction angiograms and 47% (50/106) with posterior circulation or posterior communicating artery aneurysms. Three patients with quadrigeminal PSAH were identified, two with nonaneurysmal SAH and one with a posterior circulation aneurysm. Seventeen patients (16%; 17/106) with pretruncal PSAH were identified, none of whom were found to have an aneurysm. The quadrigeminal pattern comprised 11% (2/19) of cases of pretruncal or quadrigeminal nonaneurysmal PSAH. CONCLUSION: A small subset of patients with nonaneurysmal PSAH present with blood centered in the quadrigeminal cistern, and the etiology of this pattern may be similar to that of the classic pretruncal variant. However, patients with quadrigeminal PSAH must still undergo thorough vascular imaging, including at least two digital subtraction angiograms, to exclude a ruptured aneurysm. PMID- 26151344 TI - Shoulder 3D range of motion and humerus rotation in two volleyball spike techniques: injury prevention and performance. AB - Repetitive stresses and movements on the shoulder in the volleyball spike expose this joint to overuse injuries, bringing athletes to a career threatening injury. Assuming that specific spike techniques play an important role in injury risk, we compared the kinematic of the traditional (TT) and the alternative (AT) techniques in 21 elite athletes, evaluating their safety with respect to performance. Glenohumeral joint was set as the centre of an imaginary sphere, intersected by the distal end of the humerus at different angles. Shoulder range of motion and angular velocities were calculated and compared to the joint limits. Ball speed and jump height were also assessed. Results indicated the trajectory of the humerus to be different for the TT, with maximal flexion of the shoulder reduced by 10 degrees, and horizontal abduction 15 degrees higher. No difference was found for external rotation angles, while axial rotation velocities were significantly higher in AT, with a 5% higher ball speed. Results suggest AT as a potential preventive solution to shoulder chronic pathologies, reducing shoulder flexion during spiking. The proposed method allows visualisation of risks associated with different overhead manoeuvres, by depicting humerus angles and velocities with respect to joint limits in the same 3D space. PMID- 26151345 TI - Haloarchaeal virus morphotypes. AB - Hypersaline waters and salt crystals are known to contain high numbers of haloarchaeal cells and their viruses. Both culture-dependent and culture independent studies indicate that these viruses represent a world-wide distributed reservoir of orphan genes and possibly novel virion morphotypes. To date, 90 viruses have been described for halophilic archaeal hosts, all belonging to the Halobacteriaceae family. This number is higher than that described for the members of any other archaeal family, but still very low compared to the viruses of bacteria and eukaryotes. The known haloarchaeal viruses represent icosahedral tailed, icosahedral internal membrane-containing, pleomorphic, and spindle-shaped virion morphotypes. This morphotype distribution is low, especially when compared to the astronomical number (>10(31)) of viruses on Earth. This strongly suggests that only certain protein folds are capable of making a functional virion. Viruses infecting cells belonging to any of the three domains of life are known to share similar major capsid protein folds which can be used to classify viruses into structure-based lineages. The latest observation supporting this proposal comes from the studies of icosahedral tailed haloarchaeal viruses which are the most abundant virus isolates from hypersaline environments. These viruses were shown to have the same major capsid protein fold (HK97-fold) with tailed bacteriophages belonging to the order Caudovirales and with eukaryotic herpes viruses. This proposes that these viruses have a common origin dating back to ancient times. Here we summarize the current knowledge of haloarchaeal viruses from the perspective of virus morphotypes. PMID- 26151346 TI - Corn oil versus lard: Metabolic effects of omega-3 fatty acids in mice fed obesogenic diets with different fatty acid composition. AB - Mixed results have been obtained regarding the level of insulin resistance induced by high-fat diets rich in saturated fatty acids (SFA) when compared to those enriched by polyunsaturated fatty acids (PUFA), and how metabolic effects of marine PUFA of n-3 series, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), depend on dietary lipid background. Here we compared two high-fat diets, in which the major lipid constituent was based either on SFA in the form of pork lard (LHF diet) or PUFA of n-6 series (Omega-6) as corn oil (cHF diet). Both cHF and LHF parental diets were also supplemented with EPA+DHA (~30 g/kg diet) to produce cHF+F and LHF+F diet, respectively. Male C57BL/6N mice were fed the experimental diets for 8 weeks. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps in mice fed LHF and cHF diets, and then metabolic effects of cHF+F and LHF+F diets were assessed focusing on the liver and epididymal white adipose tissue (eWAT). Both LHF and cHF induced comparable weight gain and the level of insulin resistance, however LHF-fed mice showed increased hepatic steatosis associated with elevated activity of stearoyl-CoA desaturase-1 (SCD1), and lower plasma triacylglycerol levels when compared to cHF. Despite lowering hepatic SCD1 activity, which was concomitant with reduced hepatic steatosis reaching the level observed in cHF+F mice, LHF+F did not decrease adiposity and the weight of eWAT, and rather further impaired insulin sensitivity relative to cHF+F, that tended to improve it. In conclusion, high-fat diets containing as much as ~35 weight% as lipids induce similar weight gain and impairment of insulin sensitivity irrespective whether they are based on SFA or Omega-6. Although the SFA-rich diet containing EPA+DHA efficiently reduced hepatic steatosis, it did so without a corresponding improvement in insulin sensitivity and in the absence of effect on adiposity. PMID- 26151347 TI - 8-bromo-7-methoxychrysin induces apoptosis by regulating Akt/FOXO3a pathway in cisplatin-sensitive and resistant ovarian cancer cells. AB - 8-bromo-7-methoxychrysin (BrMC), a novel chrysin analog, was reported to have anti-cancer activities. The aim of the present study was to investigate the molecular mechanism of 8-bromo-7-methoxychrysin (BrMC)-induced apoptosis via the Akt/forkhead box O3a (FOXO3a) pathway in cisplatin (DDP)-sensitive and -resistant ovarian cancer cells. The human ovarian cancer cell lines A2780 and A2780/DDP were cultured in vitro. Various molecular techniques were used to assess the expression of FOXO3a and B cell lymphoma 2 (Bcl-2)-interacting mediator of cell death (Bim) in cisplatin-sensitive and -resistant ovarian cancer cells. Different concentrations of BrMC induced apoptosis in cisplatin-sensitive and -resistant ovarian cancer cells. BrMC-induced apoptotic cell death occurred mainly by the activation of Akt, which was accompanied by the overexpression of transcription factor FOXO3a, with a concomitant increase in the expression levels of Bim. Silencing Bim expression by using small interfering RNA, attenuated the induction of apoptosis by BrMC treatment. The results indicated that BrMC-induced apoptosis in cisplatin-sensitive and -resistant ovarian cancer cells may occur via the regulation of Akt/FOXO3a, leading to Bim transcription. PMID- 26151348 TI - Enantioselective Synthesis of Dialkylated alpha-Hydroxy Carboxylic Acids through Asymmetric Phase-Transfer Catalysis. AB - In the presence of an L-tert-leucine-derived urea-ammonium salt as phase-transfer catalyst, a highly enantioselective alkylation of 5H-oxazol-4-ones with various benzyl bromides and allylic bromides has been developed to furnish catalytic asymmetric synthesis of biologically important dialkylated alpha-hydroxy carboxylic acids with a broad scope. This is the first example of an L-amino acid derived urea-ammonium salt being used as a phase-transfer catalyst with excellent catalytic efficiency. PMID- 26151349 TI - Man Up Monday: An integrated public health approach to increase sexually transmitted infection awareness and testing among male students at a midwest university. AB - OBJECTIVE: This campaign sought to (a) increase awareness of sexual health and chlamydia testing; (b) motivate students, particularly sexually active men who do not pursue regular sexually transmitted infection (STI) testing, to get tested; and (c) improve the capacity of the student health center to provide free chlamydia testing and treatment for all students. PARTICIPANTS: Students enrolled at a 4-year public research university (N = 333). METHODS: Collaborative partnerships formed the foundation of a campus marketing and testing campaign, with treatment for students testing positive for chlamydia. RESULTS: A total of 333 students were tested over 5 consecutive Mondays, showing a chlamydia incidence of 9.6%. The incidence for females and males were 8.6% and 10.8%, respectively. CONCLUSIONS: The campaign was effective in reaching men, an at-risk population not traditionally emphasized in STI testing. PMID- 26151350 TI - Child Mental Health Services in the Emergency Department: Disparities in Access. AB - OBJECTIVE: Recent research suggests that increasing numbers of caregivers are bringing their children to the emergency department (ED) for mental health services and that a large proportion of these children have Medicaid as their insurance. The objective of this study was to examine the characteristics of children with Medicaid who present with psychiatric conditions in Florida hospital EDs. METHODS: A retrospective research design was used, and the insurance claims of children who went to the ED for mental health care were analyzed. A logistic regression model was constructed to determine whether age, race, ethnicity, sex, and residence in an area with mental health professional shortage increased the odds of a psychiatric ED visit for children with Medicaid. RESULTS: All 5 predictor variables were significantly associated with the likelihood of an ED visit for mental health reasons by children with Medicaid. CONCLUSIONS: The ED is an entry point into the child mental health system of care for children with Medicaid. PMID- 26151351 TI - Cerebral Abscess Presenting as a Complex Febrile Seizure. AB - Currently, there is no standardized approach to the management of complex febrile seizures in children and there are no published practice guidelines for the procurement of neuroimaging. Presented is a 2-year-old female patient who experienced a 3- to 5-minute episode of staring and unilateral mouth twitching associated with high fever. On initial presentation, the patient appeared well and had a normal neurological examination. No focus of infection was identified, and she was diagnosed with complex febrile seizure. The patient was discharged home with close neurology and primary care follow-up but returned the following day with altered mental status, toxic appearance, and right lower extremity weakness. Magnetic resonance imaging of the brain revealed left-sided cranial empyema and the patient was managed with antibiotics and surgical drainage. A literature review to answer the question "Do children with complex febrile seizures require emergent neuroimaging?" yielded a small number of retrospective reviews describing the utility of computed tomography, magnetic resonance imaging and lumbar puncture in the work-up of febrile seizures. Current evidence indicates that neuroimaging is not indicated in an otherwise healthy child who presents with complex febrile seizure if the patient is well appearing and has no evidence of focal neurological deficit on examination. As this case demonstrates, however, serious conditions such as meningitis and brain abscess (though rare) should be considered in the differential diagnosis of complex febrile seizure and physicians should remain aware that the need for neuroimaging and/or lumbar puncture may arise in the appropriate clinical setting. PMID- 26151352 TI - Evidence for quantum effects in the predissociation of methylamine isotopologues. AB - Non-adiabatic dynamics at conical intersections (CIs) extensively affects the photostability of biomolecules by efficiently photoinducing decay routes that dissipate harmful excess ultraviolet energy. Here the predissociation of the model test molecules, methylamine (CH3NH2) and its partially deuterated isotopologue (CD3NH2), excited to different specific vibrational modes in the electronically excited state has been experimentally investigated. The H(D) photofragments were detected by two-color reduced-Doppler ion imaging, which allows measurement of their entire velocity distributions in each laser pulse. The fast and slow H products, resulting from N-H bond cleavage, obtained via different dissociation pathways, showed anomalous distributions for some vibronic states, as indicated by dynamic resonances in the product branching ratio and in the anisotropy parameters of the fast H photofragments. This vibronic-specific control is attributed to the sensitivity of the non-adiabatic dynamics to the energy difference between the initially prepared vibrational states and the energy of the CIs and not only to the distinctive pre-excited nuclear motions. The observations in the two isotopologues reveal uniquely detailed insight into the dynamics of state-specific control. PMID- 26151353 TI - Palladium(II)-Catalyzed C-H Bond Activation/C-C Coupling/Intramolecular Tsuji Trost Reaction Cascade: Facile Access to 2H-Pyranonaphthoquinones. AB - An efficient one-pot synthesis of 2H-pyranonaphthoquinone was achieved via a palladium-catalyzed C-H bond activation/C-C bond formation/intramolecular Tsuji Trost reaction cascade. The unprecedented procedure exhibits excellent functional group tolerance, giving the target naphthoquinones in moderate to good isolated yields (40-88%) under mild reaction conditions. Scalable production of the product can make this reaction a method of choice for the synthesis of 2H pyranonaphthoquinones. PMID- 26151354 TI - Higher Hepatic miR-29 Expression in Undernourished Male Rats During the Postnatal Period Targets the Long-Term Repression of IGF-1. AB - A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepatic Igf1 expression, leading to impaired growth and metabolism. Previously, we have demonstrated that the timing of nutritional restoration in perinatal life can differentially program hepatic gene expression. Although microRNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3' untranslated region of Igf1, we examined how protein restoration in maternal protein restriction rat offspring influences hepatic miR-29 and Igf1 expression in adulthood. Pregnant Wistar rats were designated into 1 of 4 dietary regimes: 20% protein (control), 8% protein during lactation only (LP-Lact), 8% protein during gestation only (LP1) or both (LP2). The steady-state expression of hepatic miR-29 mRNA significantly increased in LP2 offspring at postnatal day 21 and 130, and this was inversely related to hepatic Igf1 mRNA and body weight. Interestingly, this reciprocal association was stronger in LP-Lact offspring at postnatal day 21. Functional relevance of this in vivo relationship was evaluated by transfection of miR-29 mimics in neonatal Clone 9 rat hepatoma cells. Transfection with miR-29 suppressed Igf1 expression by 12 hours. Collectively, these findings implicate that nutritional restoration after weaning (post liver differentiation) in maternal protein restriction rat offspring fails to prevent long-term impaired growth, in part, due to miR-29 suppression of hepatic Igf1 expression. PMID- 26151356 TI - Osteocalcin Effect on Human beta-Cells Mass and Function. AB - The osteoblast-specific hormone osteocalcin (OC) was found to regulate glucose metabolism, fat mass, and beta-cell proliferation in mice. Here, we investigate the effect of decarboxylated OC (D-OC) on human beta-cell function and mass in culture and in vivo using a Nonobese diabetic-severe combined immunodeficiency mouse model. We found that D-OC at dose ranges from 1.0 to 15 ng/mL significantly augmented insulin content and enhanced human beta-cell proliferation of cultured human islets. This was paralleled by increased expression of sulfonylurea receptor protein; a marker of beta-cell differentiation and a component of the insulin-secretory apparatus. Moreover, in a Nonobese diabetic-severe combined immunodeficiency mouse model, systemic administration of D-OC at 4.5-ng/h significantly augmented production of human insulin and C-peptide from the grafted human islets. Finally, histological staining of the human islet grafts showed that the improvement in the beta-cell function was attributable to an increase in beta-cell mass as a result of beta-cell proliferation indicated by MKI67 staining together with the increased beta-cell number and decreased alpha cell number data obtained using laser scanning cytometry. Our data for the first time show D-OC-enhanced beta-cell function in human islets and support future exploitation of D-OC-mediated beta-cell regulation for developing useful clinical treatments for patients with diabetes. PMID- 26151355 TI - Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice. AB - An inflammatory response is instrumental in the physiological process of parturition but the upstream signals initiating inflammation are undefined. Because endogenous ligands for Toll-like receptor 4 (TLR4) are released in late gestation, we hypothesized that on-time labor requires TLR4 signaling, to trigger a cytokine and leukocyte response and accelerate the parturition cascade. In pregnant TLR4-deficient (Tlr4-/-) mice, average gestation length was extended by 13 hours and increased perinatal mortality was seen compared with wild-type controls. Quantification of cytokine and uterine activation gene expression showed that late gestation induction of Il1b, Il6, Il12b, and Tnf expression seen in control placenta and fetal membranes was disrupted in Tlr4-/- mice, and accompanied by a transient delay in expression of uterine activation genes, including prostaglandin F receptor, oxytocin receptor, and connexin-43. Leukocyte populations were altered before birth in TLR4-deficient females, with fewer neutrophils and macrophages in the placenta, and fewer dendritic cells and more regulatory T cells in the myometrium. Administration of TLR4 ligand lipopolysaccharide to pregnant wild-type mice induced cytokine expression and fetal loss, whereas Tlr4-/- pregnancies were protected. The small molecule TLR4 antagonist (+)-naloxone increased mean duration of gestation by 16 hours in wild type mice. Collectively, these data demonstrate that TLR4 is a key upstream regulator of the inflammatory response acting to drive uterine activation and control the timing of labor. Because causal pathways for term and preterm labor converge with TLR4, interventions to manipulate TLR4 signaling may have therapeutic utility for women at risk of preterm labor, or in postterm pregnancy. PMID- 26151357 TI - Structural and ultrastructural evaluation of the aortic wall after transplantation of bone marrow-derived cells (BMCs) in a model for atherosclerosis. AB - Stem cells are characterized by their ability to differentiate into multiple cell lineages and display the paracrine effect. The aim of this work was to evaluate the effect of therapy with bone marrow-derived cells (BMCs) on glucose, lipid metabolism, and aortic wall remodeling in mice through the administration of a high-fat diet and subsequent BMCs transplantation. C57BL/6 mice were fed a control diet (CO group) or an atherogenic diet (AT group). After 16 weeks, the AT group was divided into 4 subgroups: an AT 14 days group and AT 21 days group that were given an injection of vehicle and sacrificed after 14 and 21 days, respectively, and an AT-BMC 14 days group and AT-BMC 21 days group that were given an injection of BMCs and sacrificed after 14 and 21 days, respectively. The BMCs transplant had reduced blood glucose, triglycerides, and total cholesterol. There was no significant difference in relation to body mass between the transplanted groups and non-transplanted groups, and all were different than CO. There was no significant difference in the glycemic curve among AT 14 days, AT BMC 14 days, and AT 21 days, and these were different than the CO and the AT-BMC 21 days groups. The increased thickness of the aortic wall was observed in all atherogenic groups, but was significantly smaller in group AT-BMC 21 days compared to AT 14 days and AT 21 days. Vacuoles in the media tunic, delamination and the thinning of the elastic lamellae were observed in AT 14 days and AT 21 days. The smallest number of these was displayed on the AT-BMC 14 days and AT-BMC 21 days. Marking to CD105, CD133, and CD68 were observed in AT 14 days and AT 21 days. These markings were not observed in AT-BMC 14 days or in AT-BMC 21 days. Electron micrographs show the beneficial remodeling in AT-BMC 14 days and AT-BMC 21 days, and the structural organization was similar to the CO group. Vesicles of pinocytosis, projection of smooth muscle cells, and delamination of the internal elastic lamina are seen in groups AT 14 days and AT 21 days. Endothelial cells were preserved, and regular and continuous contour in internal elastic lamelae were observed in the CO, the AT-BMC 14 days, and AT-BMC 21 days groups. In conclusion, in an atherosclerotic model using mice and atherogenic diet, the injection of BMCs improves glucose, lipid metabolism, and causes a beneficial remodeling of the aortic wall. PMID- 26151358 TI - B7-H3 promotes cell migration and invasion through the Jak2/Stat3/MMP9 signaling pathway in colorectal cancer. AB - B7-H3, a newly identified co-stimulatory molecule, has been reported to be highly expressed in a number of types of cancer and is associated with a poor prognosis. Transwell experiments and a wound-healing assay were used to detect the role of over-expressed B7-H3 on cell migration and invasion in colorectal cancer (CRC) cells. The expression level of matrix metallopeptidase 9 (MMP-9) was further investigated by zymography experiments and western blot analysis, and involvement of the Janus kinase 2 (Jak2) signal transducer and activator of transcription 3 (STAT3) signaling pathway was determined using AG490, a Jak2 selective inhibitor. Data showed that overexpression of B7-H3 promoted cell migration and invasion in CRC. Further investigation certified that enhanced expression of B7-H3 elevated MMP-9 through upregulation of the Jak2-Stat3 signaling pathway. Due to its pro migratory and pro-invasive function, B7-H3 may serve as a therapeutic target in the treatment of CRC. PMID- 26151359 TI - Correction to Real-Time Analysis of Cellular Response to Small-Molecule Drugs within a Microfluidic Dielectrophoresis Device. PMID- 26151360 TI - Searching for Public Health Law's Sweet Spot: The Regulation of Sugar-Sweetened Beverages. AB - David Studdert and colleagues explore how to balance public health, individual freedom, and good government when it comes to sugar-sweetened drinks. PMID- 26151361 TI - Changes in Cross-Sectional Area and Transverse Diameter of the Heart on Inspiratory and Expiratory Chest CT: Correlation with Changes in Lung Size and Influence on Cardiothoracic Ratio Measurement. AB - OBJECTIVE: The aim of this study was to investigate physiological changes in cardiac area and diameters between inspiratory and expiratory chest computed tomography (CT), and to assess their correlation with lung size change and influence on cardiothoracic ratio (CTR) measurements. MATERIALS AND METHODS: The institutional review board of our institution approved this study, and informed consent was waived. Forty-three subjects underwent inspiratory and expiratory chest CT as part of routine clinical care. On both inspiratory and expiratory scans, lung volumes and maximum lung diameters (transverse and vertical directions) were measured. The maximum cardiac cross-sectional area (CSA) and the maximum transverse cardiac diameter were measured on both scans, and the CT-based CTR was calculated. Changes in the lung and cardiac measurements were expressed as the expiratory/inspiratory (E/I) ratios. Comparisons between inspiratory and expiratory measurements were made by the Wilcoxon signed-rank test. Correlations between the E/I ratios of lung and heart measurements were evaluated by Spearman's rank correlation analysis. RESULTS: Cardiac CSA and transverse cardiac diameter was significantly larger on expiratory than on inspiratory CT (p < 0.0001). Significant negative correlations were found between the E/I ratios of these cardiac measurements and the E/I ratios of lung volume and vertical lung diameter (p < 0.01). CT-based CTR was significantly larger on expiration than on inspiration (p < 0.0001). CONCLUSIONS: Heart size on chest CT depends on the phase of ventilation, and is correlated with changes in lung volume and craniocaudal lung diameter. The CTR is also significantly influenced by ventilation. PMID- 26151362 TI - Evaluating the Psychometric Quality of Social Skills Measures: A Systematic Review. AB - INTRODUCTION: Impairments in social functioning are associated with an array of adverse outcomes. Social skills measures are commonly used by health professionals to assess and plan the treatment of social skills difficulties. There is a need to comprehensively evaluate the quality of psychometric properties reported across these measures to guide assessment and treatment planning. OBJECTIVE: To conduct a systematic review of the literature on the psychometric properties of social skills and behaviours measures for both children and adults. METHODS: A systematic search was performed using four electronic databases: CINAHL, PsycINFO, Embase and Pubmed; the Health and Psychosocial Instruments database; and grey literature using PsycExtra and Google Scholar. The psychometric properties of the social skills measures were evaluated against the COSMIN taxonomy of measurement properties using pre-set psychometric criteria. RESULTS: Thirty-Six studies and nine manuals were included to assess the psychometric properties of thirteen social skills measures that met the inclusion criteria. Most measures obtained excellent overall methodological quality scores for internal consistency and reliability. However, eight measures did not report measurement error, nine measures did not report cross-cultural validity and eleven measures did not report criterion validity. CONCLUSIONS: The overall quality of the psychometric properties of most measures was satisfactory. The SSBS-2, HCSBS and PKBS-2 were the three measures with the most robust evidence of sound psychometric quality in at least seven of the eight psychometric properties that were appraised. A universal working definition of social functioning as an overarching construct is recommended. There is a need for ongoing research in the area of the psychometric properties of social skills and behaviours instruments. PMID- 26151363 TI - Transcriptional Responses Associated with Virulence and Defence in the Interaction between Heterobasidion annosum s.s. and Norway Spruce. AB - Heterobasidion annosum sensu lato is a serious pathogen causing root and stem rot to conifers in the northern hemisphere and rendering the timber defective for sawing and pulping. In this study we applied next-generation sequencing to i) identify transcriptional responses unique to Heterobasidion-inoculated Norway spruce and ii) investigate the H. annosum transcripts to identify putative virulence factors. To address these objectives we wounded or inoculated 30-year old Norway spruce clones with H. annosum and 454-sequenced the transcriptome of the interaction at 0, 5 and 15 days post inoculation. The 491,860 high-quality reads were de novo assembled and the relative expression was analysed. Overall, very few H. annosum transcripts were represented in our dataset. Three delta-12 fatty acid desaturase transcripts and one Clavaminate synthase-like transcript, both associated with virulence in other pathosystems, were found among the significantly induced transcripts. The analysis of the Norway spruce transcriptional responses produced a handful of differentially expressed transcripts. Most of these transcripts originated from genes known to respond to H. annosum. However, three genes that had not previously been reported to respond to H. annosum showed specific induction to inoculation: an oxophytodienoic acid reductase (OPR), a beta-glucosidase and a germin-like protein (GLP2) gene. Even in a small data set like ours, five novel highly expressed Norway spruce transcripts without significant alignment to any previously annotated protein in Genbank but present in the P. abies (v1.0) gene catalogue were identified. Their expression pattern suggests a role in defence. Therefore a more complete survey of the transcriptional responses in the interactions between Norway spruce and its major pathogen H. annosum would probably provide a better understanding of gymnosperm defence than accumulated until now. PMID- 26151364 TI - Nitric Oxide Mediates 5-Aminolevulinic Acid-Induced Antioxidant Defense in Leaves of Elymus nutans Griseb. Exposed to Chilling Stress. AB - Nitric oxide (NO) and 5-aminolevulinic acid (ALA) are both extremely important signalling molecules employed by plants to control many aspects of physiology. In the present study, the role of NO in ALA-induced antioxidant defense in leaves of two sources of Elymus nutans Griseb. (Damxung, DX and Zhengdao, ZD) was investigated. Chilling stress enhanced electrolyte leakage, accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2) and superoxide radical in two E. nutans, which were substantially alleviated by exogenous ALA and NO application. Pretreatment with NO scavenger PTIO or NOS inhibitor L-NNA alone and in combination with ALA induced enhancements in electrolyte leakage and the accumulation of MDA, H2O2 and superoxide radical in leaves of DX and ZD exposed to chilling stress, indicating that the inhibition of NO biosynthesis reduced the chilling resistance of E. nutans and the ALA-enhanced chilling resistance. Further analyses showed that ALA and NO enhanced antioxidant defense and activated plasma membrane (PM) H+-ATPase and decreased the accumulation of ROS induced by chilling stress. A pronounced increase in nitric oxide synthase (NOS) activity and NO release by exogenous ALA treatment was found in chilling resistant DX plants exposed to chilling stress, while only a little increase was observed in chilling-sensitive ZD. Furthermore, inhibition of NO accumulation by PTIO or L-NNA blocked the protective effect of exogenous ALA, while both exogenous NO treatment and inhibition of endogenous NO accumulation did not induce ALA production. These results suggested that NO might be a downstream signal mediating ALA-induced chilling resistance in E. nutans. PMID- 26151365 TI - Investigating Factors Associated with Depression of Type 2 Diabetic Retinopathy Patients in China. AB - AIMS AND OBJECTIVES: To assess the depression status of type 2 diabetic retinopathy patients in Nantong China and to identify factors associated with depression. METHODS: Two hundred and ninety-four patients with type 2 diabetic retinopathy were recruited from the Affiliated Hospital of Nantong University. The severity of DR was measured in the worse eye. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D); the quality of life was measured with the Medical Outcomes Study Short Form 36 (SF 36). The logistic regression analyses were used to identify the independent factors of depression. RESULTS: The mean age of the study subjects was 57.77 years (SD: 9.64). Approximately 35.7% of subjects reported depressive symptoms (n = 105).Multiple logistic regression analyses showed that female gender (p = 0.014), low monthly income (p = 0.01), poor vision in the better eye (P = 0.002), laser treatment history (p = 0.01) were significant risk factors for depression. The quality of life of individuals with CES-D score<16 was significantly better compared with individuals with CES-D score>=16. CONCLUSION: The reported depressive symptoms among type 2 diabetic retinopathy population is higher in Nantong China. Gender, salary, vision acuity and treatment history were important risk factors linked to this disorder in the Chinese type 2 diabetic retinopathy population from Nantong. More attention by medical care personnel needs to be paid to the psychological health of this population. PMID- 26151366 TI - How Psychological Science Informs the Teaching of Reading. AB - This monograph discusses research, theory, and practice relevant to how children learn to read English. After an initial overview of writing systems, the discussion summarizes research from developmental psychology on children's language competency when they enter school and on the nature of early reading development. Subsequent sections review theories of learning to read, the characteristics of children who do not learn to read (i.e., who have developmental dyslexia), research from cognitive psychology and cognitive neuroscience on skilled reading, and connectionist models of learning to read. The implications of the research findings for learning to read and teaching reading are discussed. Next, the primary methods used to teach reading (phonics and whole language) are summarized. The final section reviews laboratory and classroom studies on teaching reading. From these different sources of evidence, two inescapable conclusions emerge: (a) Mastering the alphabetic principle (that written symbols are associated with phonemes) is essential to becoming proficient in the skill of reading, and (b) methods that teach this principle directly are more effective than those that do not (especially for children who are at risk in some way for having difficulty learning to read). Using whole-language activities to supplement phonics instruction does help make reading fun and meaningful for children, but ultimately, phonics instruction is critically important because it helps beginning readers understand the alphabetic principle and learn new words. Thus, elementary-school teachers who make the alphabetic principle explicit are most effective in helping their students become skilled, independent readers. PMID- 26151367 TI - AIDing cancer treatment: Reducing AID activity via HSP90 inhibition. AB - The activation induced deaminase (AID) catalyses the two key events underlying humoral adaptive immunity: class switch recombination and somatic hypermutation of antibody genes in B lymphocytes. AID accomplishes this task by directly deaminating cytosines within the genomic immunoglobulin locus, thereby triggering a complex mutagenic process eventually leading to improved effector function of antibodies. However, it has long been noticed that AID can be aberrantly expressed in cancer and that its activity is not absolutely restricted to antibody genes, as substantial genome-wide off-target mutations have been observed, which contribute to tumorigenesis and clonal evolution of AID expressing malignancies. In this issue of the European Journal of Immunology, Montamat-Sicotte et al. [Eur. J. Immunol. 2015. 45: 2365-2376] investigate the feasibility and efficacy of in vivo inhibition of AID with HSP90 inhibitors in a mouse model of B-cell leukemia and in vitro with a human breast cancer cell line, thereby demonstrating that cancer patients may benefit from preventing noncanonical AID functions. PMID- 26151368 TI - Systemic vasoconstriction modulates the responses of pulmonary vasculature and airway to vasoconstrictors in anesthetized rats. AB - PURPOSE: The physiological responses of the pulmonary vasculature and airway to various vasoconstrictors were studied using isolated perfused lungs and pulmonary arteries, but these responses were not systematically studied in in vivo rats. We determined these responses and modulating effects of systemic circulation in anesthetized rats. METHODS: We measured directly pulmonary arterial pressure (PAP), left atrial pressure (LAP), aortic blood flow, and airway pressure (AWP) to determine pulmonary vascular resistance (PVR), following injections of angiotensin II (ANG II), endothelin-1 (ET-1), vasopressin, phenylephrine and thromboxane A2 mimetic U46619 in anesthetized SD rats. RESULTS: ANG II, phenylephrine and vasopressin at high doses caused strong systemic vasoconstriction and left heart overload, resulting in a transient increase in LAP and pulmonary congestion, which consequently decreased PVR. Nonetheless, prior to LAP elevation, PVR was slightly but significantly increased by ANG II and phenylephrine. In contrast, ET-1 and U46619 substantially increased PVR in the absence of LAP elevation, while vasopressin did not increase PVR. In separate experiments, PAP and AWP increased when LAP was forcedly elevated. AWP was increased by U46619 through bronchoconstriction and by the other agents through increased LAP-induced pulmonary congestion. CONCLUSION: Airway constriction is induced by U46619, and pulmonary vasoconstriction is induced strongly by U46619 and ET-1, and weakly by ANG II and phenylephrine, but not by vasopressin in anesthetized rats. ANG II, vasopressin and phenylephrine exert indirectly a transient pulmonary vasodilatory action due to pulmonary congestion evoked by strong systemic vasoconstriction, which may account for weak pulmonary pressor responses to these agents. PMID- 26151369 TI - The Great Imitator: Ocular Syphilis Presenting as Posterior Uveitis. AB - BACKGROUND: Syphilis is often known as the "Great Imitator". The differential diagnosis of posterior uveitis is broad with ocular syphilis being particularly challenging to diagnose as it presents similarly to other ocular conditions such as acute retinal necrosis. CASE REPORT: A 34-year-old woman with multiple sexual partners over the past few years presented with painful and progressively worsening unilateral vision loss for 2 weeks. Several months prior, she had reported non-specific symptoms of headache and diffuse skin rash. Despite treatment with oral acyclovir for 3 weeks, her vision progressively declined, and she was referred to the university ophthalmology clinic for further evaluation. On examination, there was concern for acute retinal necrosis and she was empirically treated with parenteral acyclovir while awaiting further infectious disease study results. Workup ultimately revealed ocular syphilis, and neurosyphilis was additionally confirmed with cerebrospinal fluid studies. Treatment with intravenous penicillin was promptly initiated with complete visual recovery. CONCLUSIONS: Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis, especially with a history of headache and skin rashes. However, given that acute retinal necrosis is a more common cause of posterior uveitis and can rapidly result in permanent vision loss, it should be empirically treated whenever it is suspected while simultaneous workup is conducted to evaluate for alternative diagnoses. PMID- 26151370 TI - Finding the music of speech: Musical knowledge influences pitch processing in speech. AB - Few studies comparing music and language processing have adequately controlled for low-level acoustical differences, making it unclear whether differences in music and language processing arise from domain-specific knowledge, acoustic characteristics, or both. We controlled acoustic characteristics by using the speech-to-song illusion, which often results in a perceptual transformation to song after several repetitions of an utterance. Participants performed a same different pitch discrimination task for the initial repetition (heard as speech) and the final repetition (heard as song). Better detection was observed for pitch changes that violated rather than conformed to Western musical scale structure, but only when utterances transformed to song, indicating that music-specific pitch representations were activated and influenced perception. This shows that music-specific processes can be activated when an utterance is heard as song, suggesting that the high-level status of a stimulus as either language or music can be behaviorally dissociated from low-level acoustic factors. PMID- 26151371 TI - Mechano-induced reversible colour and luminescence switching of a gold(i) diphosphine complex. AB - A gold(i)-diphosphine simultaneously exhibits reversible mechanochromism and mechanochromic luminescence. The mechanical grinding can trigger a transformation from a neutral mononuclear structure exhibiting white colour and blue photoluminescence to an ionic dinuclear structure with intramolecular aurophilic interactions exhibiting yellow colour and red emission. PMID- 26151372 TI - Evidence of plasticity in the dengue virus: Host cell interaction. AB - Dengue virus (DENV) is the most important mosquito transmitted human viral pathogen. There are four different dengue viruses (DENV 1 to DENV 4) with multiple genotypes and strains. Whether there are significant differences in how these DENVs interact with and modulate the host cell proteome remains unclear. Using a panel of 12 DENVs representative of one isolate for each DENV from three different origins (lab adapted, low passage isolates from dengue fever patients, low passage isolates from dengue hemorrhagic fever patients) LLC-MK2 cells were equally infected and proteomic alterations compared by MALDI-TOF and principal component analysis and a sub-10 kDa peptidome analysis. There was no clear segregation of data with respect to either virus origin or serotype in either the MALDI-TOF or the peptidome analysis. The two isolates with the greatest variation from the other isolates in the MALDI-TOF analysis were a low passage DENV 3 dengue fever isolate and a low passage DENV 4 dengue hemorrhagic fever isolate. Analysis of the sub-10 kda protein fraction by LC-MS/MS identified 128 proteins of which only 28 (20%) were constantly expressed in all infections, while 80% showed variable expression, with no clear relationship with either serotype or virus origin. These results suggest that the interaction between DENV and the host cell is characterized by a degree of plasticity, whereby the end biological processes are not rigorously determined by specific proteome alterations, and that virus strain plays a role in determining the specific proteome changes. PMID- 26151373 TI - Elucidating the roles of gut neuropeptides on channel catfish feed intake, glycemia, and hypothalamic NPY and POMC expression. AB - Both intrinsic and extrinsic factors modulate food intake and glycemia in vertebrates, in part through interactions with hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons. The objective of this project was to elucidate the effects of ghrelin (GHRL), gastrin-releasing peptide (GRP), cholecystokinin (CCK), glucagon-like peptide (GLP), pancreatic polypeptide (PP), and peptide YY (PYY) on appetite, glycemia, and hypothalamic expression of NPY and POMC in channel catfish. Catfish were injected intraperitoneally with a single peptide at concentrations of either 0 (control), 50, 100, or 200 ng/g body weight (BW), respectively. Fish were allowed to recover for 30 min, and then fed to satiation over 1 h. Feed intake was determined 1h post-feeding. Catfish injected with GHRL at 50 and 100 ng/g BW and GRP at 200 ng/g BW consumed significantly (P<0.05) less feed compared to controls. A tendency (P<0.1) to suppress feed intake was also observed in the 200 ng/g BW GHRL and PP treatments. PYY, CCK, and GLP had no effects on feed intake. Glycemia was not affected by GHRL, GRP, PP, and PYY treatments, but was suppressed by CCK. A tendency toward lower plasma glucose concentrations was observed in fish administered GLP at 50 ng/g BW. Hypothalamic NPY expression was highly variable and not significantly affected by treatment. POMC expression was also variable, but tended to be reduced by the highest concentration of CCK. These results provide new insight into the roles and regulation of gut neuropeptides in catfish appetite and glycemia. PMID- 26151374 TI - Unphosphorylated HSP27 (HSPB1) regulates the translation initiation process via a direct association with eIF4E in osteoblasts. AB - Heat-shock protein 27 (HSP27/HSPB1) and its phosphorylation are implicated in multiple physiological and pathophysiological cell functions. Our previous study reported that unphosphorylated HSP27 has an inhibitory role in triiodothyronine (T(3))-induced osteocalcin (OC) synthesis in osteoblasts. However, the mechanisms behind the HSP27-mediated effects on osteoblasts remain to be clarified. In the present study, to investigate the exact mechanism of HSP27 and its phosphorylation in osteoblasts, the molecular targets of HSP27 were explored using osteoblast-like MC3T3-E1 cells. The levels of OC mRNA induced by T(3) in the HSP27-overexpressing cells did not show any significant differences compared with those in the control empty vector-transfected cells. Therefore, the interactions between HSP27 and translational molecules were focused on, including eukaryotic translation initiation factor 4E (eIF4E), eIF4G and 4E-binding protein 1 (4E-BP1). The HSP27 protein in the unstimulated cells co-immunoprecipitated with eIF4E, but not eIF4G or 4E-BP1. In addition, the association of eIF4E with 4E-BP1 was observed in the HSP27-overexpressing cells, as well as in the control cells. Under T(3) stimulation, the binding of eIF4E to eIF4G was markedly attenuated in the HSP27-overexpressing cells compared with the control cells. In addition, the binding of HSP27 to eIF4E in the unstimulated cells was diminished by the phosphorylation of HSP27. In response to T(3) stimulation, the association of eIF4E with eIF4G in the unphosphorylatable HSP27-overexpressing cells was markedly reduced compared with the phospho-mimic HSP27-overexpressing cells. Taken together, these findings strongly suggest that unphosphorylated HSP27 associates with eIF4E in osteoblasts and suppresses the translation initiation process. PMID- 26151375 TI - Impact of Sediment on Agrichemical Fate and Bioavailability to Adult Female Fathead Minnows: A Field Study. AB - Precipitation induced runoff is an important pathway for agrichemicals to enter surface water systems and expose aquatic organisms to endocrine-disrupting compounds such as pesticides and steroid hormones. The objectives of this study were to investigate the distribution of agrichemicals between dissolved and sediment-bound phases during spring pulses of agrichemicals and to evaluate the role of suspended sediment in agrichemical bioavailability to aquatic organisms. To accomplish these objectives, suspended sediment and water samples were collected every 3 days from a field site along the Elkhorn River, located at the downstream end of a heavily agricultural watershed, and were screened for 21 pesticides and 21 steroids. Adult female fathead minnows (Pimephales promelas) were exposed in field mesocosms to river water containing varying sediment loads. Changes in organism hepatic gene expression of two estrogen-responsive genes, vitellogenin (VTG) and estrogen receptor alpha (ERalpha), as well as the androgen receptor (AR) were analyzed during periods of both low and high river discharge. Trends in agrichemical concentrations of both the dissolved and sediment phases as a function of time show that, while sediment may act as both a source and a sink for agrichemicals following precipitation events, the overall driver for molecular defeminization in this system is direct exposure to the sediment associated compounds. This study suggests that endocrine disrupting effects observed in organisms in turbid water could be attributed to direct exposure of contaminated sediment. PMID- 26151376 TI - The aquatic impact of ionic liquids on freshwater organisms. AB - Ionic liquids (ILs), also known as liquid electrolytes, are powerful solvents with a wide variety of academic and industrial applications. Bioassays with aquatic organisms constitute an effective tool for the evaluation of ILs' toxicity, as well as for the prediction and identification of possible moieties that act as toxicophores. In this work, the acute toxicity of six ILs and two commonly used organic solvents was evaluated using freshwater organisms: Daphnia magna, Raphidocelis subcapitata and Hydra attenuata. The bioassays were performed by exposing the organisms to increasing concentrations of the ILs and observing D. magna immobilization, R. subcapitata growth inhibition, and the morphological or mortality effects in H. attenuata. The results demonstrate that the tested organisms are not equally susceptible to the ILs, e.g., bmpyr [BF4] was the least toxic compound for R. subcapitata, N1,1 [N1,1,1OOH] for D. magna and emim [Tf2N] for H. attenuata. This highlights the importance of applying a battery of assays in toxicological analysis. Additionally, Hydra proved to be the most tolerant species to the tested ILs. According to their hazard rankings, the tested ILs are considered practically harmless or moderately toxic, except (Hex)3(TDec)P [Cl], which was classified as highly toxic. The ILs were revealed to be more harmful to aquatic systems than the tested organic solvents, reaffirming the need to analyze carefully the (eco)toxicological impact of these compounds. The present study provides additional data in the evaluation of the potential hazard and the impact of ILs in the environment. PMID- 26151377 TI - Association of polycyclic aromatic hydrocarbons (PAHs) and lead co-exposure with child physical growth and development in an e-waste recycling town. AB - Informal e-waste recycling activities results in serious environmental pollution of PAHs. We evaluated the body burden of 16 PAH congeners and potential health risks for children. A total of 167 children from exposed and reference area entered this study. Child blood samples were collected; height, weight, head and chest circumferences were measured. Blood PAH and lead concentrations were determined. The blood median of total PAHs from the exposed group was significantly higher than the reference group (68.53MUg/L vs. 26.92MUg/L, P<0.01). The major sources of Sigma16-PAH and Sigma7 carcinogenic-PAH were residence adjacent to e-waste workshop, paternal occupation related to e-waste recycling and house as a workshop. Inverse correlations were observed in the age and milk consumption with these two PAH groups, while a positive association was found between BMI and Sigma7 carcinogenic-PAH, and between child height and blood lead. When divided into high and low exposure groups by Sigma16-PAH, a significant negative association was found between body height and blood PAHs (beta and 95%CI: -3.838, -6.469 to -1.206), while for weight and chest circumferences, negative associations were obtained only in the male subgroup before adjustment. After adjustment by sex, age, child milk products consumption per month and blood lead, child height was negatively associated with Sigma16-PAH (beta and 95%CI: -3.884, -6.736 to -1.033). Same trends were observed for child chest circumference (beta and 95%CI: -1.147, -2.229 to -0.065). We suggest a negative association of PAHs and child height and chest circumference, while the correlation is more obvious in boys. PMID- 26151379 TI - [Intraosseous Tophaceous Gout of the Hand: Case Report and Literature Review]. AB - We report on an intraosseous gout manifestation in the middle phalanx of the left index finger of a 54-year-old patient. PMID- 26151378 TI - Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography. AB - Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of (18)F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse (18)F NaF binding. We show that (18)F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. (18)F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of (18)F-NaF may foster new approaches to developing treatments for vascular calcification. PMID- 26151380 TI - Trace organic contaminants in biosolids: Impact of conventional wastewater and sludge processing technologies and emerging alternatives. AB - This paper critically reviews the fate of trace organic contaminants (TrOCs) in biosolids, with emphasis on identifying operation conditions that impact the accumulation of TrOCs in sludge during conventional wastewater and sludge treatment and assessing the technologies available for TrOC removal from biosolids. The fate of TrOCs during sludge thickening, stabilisation (e.g. aerobic digestion, anaerobic digestion, alkaline stabilisation, and composting), conditioning, and dewatering is elucidated. Operation pH, sludge retention time (SRT), and temperature have significant impact on the sorption and biodegradation of TrOCs in activated sludge that ends up in the sludge treatment line. Anaerobic digestion may exacerbate the estrogenicity of sludge due to bioconversion to more potent metabolites. Application of advanced oxidation or thermal pre-treatment may minimise TrOCs in biosolids by increasing the bioavailability of TrOCs, converting TrOCs into more biodegradable products, or inducing complete mineralisation of TrOCs. Treatment of sludge by bioaugmentation using various bacteria, yeast, or fungus has the potential to reduce TrOC levels in biosolids. PMID- 26151381 TI - Enhanced selective removal of Cu(II) from aqueous solution by novel polyethylenimine-functionalized ion imprinted hydrogel: Behaviors and mechanisms. AB - A novel polyethylenimine-functionalized ion-imprinted hydrogel (Cu(II) p(PEI/HEA)) was newly synthesized by (60)Co-gamma-induced polymerization for the selective removal of Cu(II) from aqueous solution. The adsorption performances including the adsorption capacity and selectivity of the novel hydrogel were much better than those of similar adsorbents reported. The hydrogel was characterized via scanning electron microscope, transmission electron microscopy, Fourier transform infrared spectra, thermal gravimetric analysis and X-ray photoelectron spectroscopy to determine the structure and mechanisms. The adsorption process was pH and temperature sensitive, better fitted to pseudo-second-order equation, and was Langmuir monolayer adsorption. The maximum adsorption capacity for Cu(II) was 40.00 mg/g. The selectivity coefficients of ion-imprinted hydrogel for Cu(II)/Pb(II), Cu(II)/Cd(II) and Cu(II)/Ni(II) were 55.09, 107.47 and 63.12, respectively, which were 3.93, 4.25 and 3.53 times greater than those of non imprinted hydrogel, respectively. Moreover, the adsorption capacity of Cu(II) p(PEI/HEA) could still keep more than 85% after four adsorption-desorption cycles. Because of such enhanced selective removal performance and excellent regeneration property, Cu(II)-p(PEI/HEA) is a promising adsorbent for the selective removal of copper ions from wastewater. PMID- 26151382 TI - Occurrence, fate and risk assessment of parabens and their chlorinated derivatives in an advanced wastewater treatment plant. AB - In the present study, parabens, p-hydroxybenzoic acid (PHBA) and chlorinated derivatives, were simultaneously determined in wastewater and sludge samples along the whole process in an advanced wastewater treatment plant (WWTP). Nine target compounds were detected in this WWTP, and methylparaben and PHBA were the dominant compounds in these samples. It is noteworthy that octylparaben with longer chain was firstly detected in this work. Mass balance results showed that 91.8% of the initial parabens mass loading was lost mainly due to degradation, while the contribution of sorption and output of primary and excess sludge was much less (7.5%), indicating that biodegradation played a significant role in the removal of parabens during the conventional treatment process. Specifically, parabens were mainly degraded in the anaerobic tank, and PHBA could be effectively removed at high rates after the advanced treatment. However, both biodegradation and adsorption accounted for minor contribution to the removal of chlorinated parabens during conventional treatment process, and they were only scantly removed by conventional treatment (33.9-40.7%) and partially removed by advanced treatment (59.2-82.8%). Risk assessment indicated that parabens and their chlorinated derivatives in second and tertiary effluent are not likely to produce biological effects on aquatic ecosystems. PMID- 26151383 TI - Kinetic and mechanistic investigations of the degradation of sulfamethazine in heat-activated persulfate oxidation process. AB - Sulfamethazine (SMZ) is widely used in livestock feeding and aquaculture as an antibiotic agent and growth promoter. Widespread occurrence of SMZ in surface water, groundwater, soil and sediment has been reported. In this study, degradation of SMZ by heat-activated persulfate (PS) oxidation was investigated in aqueous solution. Experimental results demonstrated that SMZ degradation followed pseudo-first-order reaction kinetics. The pseudo-first-order rate constant (kobs) was increased markedly with increasing concentration of PS and temperature. Radical scavenging tests revealed that the predominant oxidizing species was SO4.(-) with HO playing a less important role. Aniline moiety in SMZ molecule was confirmed to be the reactive site for SO4.(-) attack by comparison with substructural analogs. Nontarget natural water constituents affected SMZ removal significantly, e.g., Cl(-) and HCO3(-) improved the degradation while fulvic acid reduced it. Reaction products were enriched by solid phase extraction (SPE) and analyzed by liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (LC-ESI-MS/MS). 6 products derived from sulfonamide S--N bond cleavage, aniline moiety oxidation and Smiles-type rearrangement were identified, and transformation pathways of SMZ oxidation were proposed. Results reveal that heat-activated PS oxidation could be an efficient approach for remediation of water contaminated by SMZ and related sulfonamides. PMID- 26151385 TI - Hyper-branched polymer grafting graphene oxide as an effective flame retardant and smoke suppressant for polystyrene. AB - A well-defined functionalized graphene oxide (FGO) grafted by hyper-branched flame retardant based on N-aminoethyl piperazine and phosphonate derivative was synthesized to reduce flammability and toxicity of polystyrene (PS). The chemical structure, morphological and thermal properties were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy and thermogravimetric analysis, respectively. Micro combustion calorimeter and steady state tube furnace were employed to evaluate the heat and non-heat fire hazards of PS nanocomposites. The incorporation of FGO into PS matrix effectively improved the flame retardancy and restrained the toxicity of the volatiles escaped, which is attributed to that the homogeneous dispersion of FGO in the PS matrix enhanced barrier effect that reduced peak heat release rate, total heat release and toxic gas release during combustion. Furthermore, PS-FGO nanocompsites obviously decreased the amount of flammable and toxic volatiles evolved, such as the aromatic compounds, carbonyl compounds, carbon monoxide, indicating suppressed fire hazards of the PS composites. PMID- 26151384 TI - Exploiting the intrinsic microbial degradative potential for field-based in situ dechlorination of trichloroethene contaminated groundwater. AB - Bioremediation of trichloroethene (TCE) polluted groundwater is challenging, with limited next generation sequencing (NGS) derived information available on microbial community dynamics associated with dechlorination. Understanding these dynamics is important for designing and improving TCE bioremediation. In this study, biostimulation (BS), biostimulation-bioaugmentation (BS-BA) and monitored natural attenuation (MNA) approaches were applied to contaminated groundwater wells resulted in >= 95% dechlorination within 7 months. Vinyl chloride's final concentrations in stimulated wells were between 1.84 and 1.87 MUg L(-1), below the US EPA limit of 2.0 MUg L(-1), compared to MNA (4.3 MUg L(-1)). Assessment of the groundwater microbial community with qPCR showed up to ~ 50-fold increase in the classical dechlorinators' (Geobacter and Dehalococcoides sp.) population post treatment. Metagenomic assays revealed shifts from Gammaproteobacteria (pre treatment) to Epsilonproteobacteria and Deltaproteobacteria (post-treatment) only in stimulated wells. Although stimulated wells were functionally distinct from MNA wells post-treatment, substantial dechlorination in all the wells implied some measure of redundancy. This study, one of the few NGS-based field studies on TCE bioremediation, provides greater insights into dechlorinating microbial community dynamics which should be useful for future field-based studies. PMID- 26151386 TI - Effect of pH with different purified aluminum species on coagulation performance and membrane fouling in coagulation/ultrafiltration process. AB - The influences of solution pH on coagulation/ultrafiltration (C-UF) process were investigated by using three purified Al species of polyaluminium chloride (PACl). A series of online-simulation experiments were developed to assess the coagulation removal efficiencies (turbidity, UV254), floc properties and membrane fouling in this paper. The results showed that change of pH had a significant impact on coagulation efficiencies, floc properties, membrane flux as well as the whole process. Under acidic condition, the hydrolysis action of aluminum salts was restrained which is bad for charge neutralization. While under alkaline region, absorption was the dominant mechanism to combine HA-Kaolin. Meanwhile, HA is apt to soluble by deprotonating under alkaline region which is hard to remove. These common effects made the experiment results complex. HA removal efficiency of Ala and Alb were higher than that of Alc, but the turbidity removal by Alc was slightly higher under the same pH condition. Flocs generated by Ala at pH 6 had advantages such as larger size and the most loosely structure which contributed the most to alleviating membrane fouling. Membrane fouling with Alb and Alc in alkaline range was more serious than that in acidic range. PMID- 26151387 TI - Relationships between Chemical Characteristics and Phytotoxicity of Biochar from Poultry Litter Pyrolysis. AB - Three biochars were prepared by intermediate pyrolysis from poultry litter at different temperatures (400, 500, and 600 degrees C with decreasing residence times) and compared with biochars from corn stalk prepared under the same pyrolysis conditions. The phytotoxicity of these biochars was estimated by means of seed germination tests on cress (Lepidium sativum L.) conducted in water suspensions (at 2, 5, and 40 g/L) and on biochars wetted according to their water holding capacity. Whereas the seeds germinated after 72 h in water suspensions with corn stalk biochar were similar to the control (water only), significant inhibition was observed with poultry litter biochars. In comparison to corn stalk, poultry litter generated biochars with higher contents of ash, ammonium, nitrogen, and volatile fatty acids (VFAs) and a similar concentration of polycyclic aromatic hydrocarbons (PAHs). Results from analytical pyrolysis (Py-GC MS) indicated that nitrogen-containing organic compounds (NCCs) and aliphatic components were distinctive constituents of the thermally labile fraction of poultry litter biochar. The inhibition of germination due to poultry litter biochar produced at 400 degrees C (PL400) was suppressed after solvent extraction or treatment with active sludge. A novel method based on solid-phase microextraction (SPME) enabled the identification of mobile organic compounds in PL400 capable of being released in air and water, including VFAs and NCCs. The higher phytotoxicity of poultry litter than corn biochars was tentatively attributed to hydrophilic biodegradable substances derived from lipids or proteins removable by water leaching or microbial treatments. PMID- 26151388 TI - Enteric epithelial cells support growth of Hymenolepis diminuta in vitro and trigger TH2-promoting events in a species-specific manner. AB - Knowledge of the gut epithelium in modulating immune responses to cestode parasites is scant. Hymenolepis diminuta causes no damage to its rodent host and is expelled from mice. Hymenolepis diminuta (scolex+2cm strobila) was cultured with rat (IEC6), human (T84) or mouse (IEC4) epithelial cell lines: all promoted worm survival, but those cultured on IEC6 (rat is a permissive host) were the healthiest. In contrast, production of Th2 polarising cytokines, IL-17e, IL-33 and TSLP, was greatest in IEC4 cells, less in T84 epithelia and almost negligible in IEC6 cells. Thus, the enteric epithelium is a key determinant of the response to infection with H. diminuta and is predictive of host permissiveness. PMID- 26151389 TI - Planning parenthood: Health care providers' perspectives on pregnancy intention, readiness, and family planning. AB - A major health care goal in the United States is increasing the proportion of pregnancies that are planned. While many studies examine family planning from the perspective of individual women or couples, few investigate the perceptions and practices of health care providers, who are gatekeepers to medicalized fertility control. In this paper, I draw on 24 in-depth interviews with providers to investigate how they interpret and enact the objective to "plan parenthood" and analyze their perspectives in the context of broader discourses about reproduction, family planning, and motherhood. Interviews reveal two central discourses: one defines pregnancy planning as an individual choice, that is as patients setting their own pregnancy intentions; the second incorporates normative expectations about what it means to be ready to have a baby that exclude poor, single, and young women. In the latter discourse, planning is a broader process of achieving middle-class life markers like a long-term relationship, a good job, and financial stability, before having children. Especially illuminating are cases where a patient's pregnancy intention and the normative expectations of "readiness" do not align. With these, I demonstrate that providers may prioritize normative notions of readiness over a patient's own intentions. I argue that these negotiations of intention and readiness reflect broader tensions in family planning and demonstrate that at times the seemingly neutral notion of "planned parenthood" can mask a source of stratification in reproductive health care. PMID- 26151390 TI - Energy expenditure on recreational visits to different natural environments. AB - Physical inactivity poses a significant challenge to physical and mental health. Environmental approaches to tackle physical inactivity have identified natural environments as potentially important public health resources. Despite this, little is known about characteristics of the activity involved when individuals visit different types of natural environment. Using Natural England's Monitor of Engagement with the Natural Environment Survey, we examined 71,603 English respondents' recreational visits to natural environments in the past week. Specifically, we examined the intensity of the activities they undertook on the visits (METs), the duration of their visit, and the associated total energy expenditure (MET minutes). Visits to countryside and urban greenspace environments were associated with more intense activities than visits to coastal environments. However, visits to coastal environments were associated with the most energy expenditure overall due to their relatively long duration. Results differed by the urbanity or rurality of the respondent's residence and also how far respondents travelled to their destination. Knowledge of what types of natural environment afford the highest volumes and intensities of physical activity could inform landscape architecture and exercise prescriptions. Isolating activity-supporting characteristics of natural environments that can be translated into urban design is important in providing physical activity opportunities for those less able to access expansive environments. PMID- 26151392 TI - CD44 alternative splicing and hnRNP A1 expression are associated with the metastasis of breast cancer. AB - CD44 is a transmembrane receptor for hyaluronic acid. CD44 pre-mRNA contains 19 exons, 9 of which are alternatively spliced. Among the CD44 spliced variants, the v4-7 variant, one of the v6 exon-containing isoforms that contains variable exon 4, 5, 6 and 7, confers metastatic potential to non-metastatic cells. Splicing of CD44 and the function of CD44 isoforms are different in breast cancer cells. hnRNP A1 is a ubiquitously expressed protein with an inhibitory function in pre mRNA splicing. We showed that CD44v6 isoform, which includes all of the v6 containing mRNA isoforms, had the highest expression level in non-metatatic breast cancer cells (MCF7) when compared to the level in metastatic breast cancer cells (MDA-MB-231) and normal breast cells (MCF10A). Furthermore we showed that hnRNP A1 knockdown regulated splicing of CD44 differently in breast cancer cells. We showed here that CD44 isoform expression is completely different in MDA-MB-231 cells than that in MCF7 and MCF10A cells, whereas MCF7 and MCF10A cells had a similar expression pattern of CD44 isoforms. RT-PCR analysis of CD44v6 showed that MCF7 and MCF10A cells predominantly expressed the c5v6v7v8v9v10c6 isoform. However, in addition to this isoform, MDA-MB-231 cells also expressed the c5v6v8v9v10c6 and c5v6c6 isoforms. We also found that knockdown of hnRNP A1 significantly reduced the expression of c5v6v7v8v9v10c6 and c5v6v8v9v10c6, and promoted the expression of c5v6c6. hnRNP A1 knockdown significantly induced cell death. In addition, hnRNP A1 knockdown induced a decrease in cell invasion in the MDA-MB-231 cells. Our results indicate that the knockdown of hnRNP A1 has a specific function on the splicing of CD44 in breast cancer cells. PMID- 26151391 TI - Gender, stress in childhood and adulthood, and trajectories of change in body mass. AB - Despite substantial evidence of the linkage between stress and weight change, previous studies have not considered how stress trajectories that begin in childhood and fluctuate throughout adulthood may work together to have long-term consequences for weight change. Working from a stress and life course perspective, we investigate the linkages between childhood stress, adulthood stress and trajectories of change in body mass (i.e., Body Mass Index, BMI) over time, with attention to possible gender variation in these processes. Data are drawn from a national longitudinal survey of the Americans' Changing Lives (N = 3617). Results from growth curve analyses suggest that both women and men who experienced higher levels of childhood stress also report higher levels of stress in adulthood. At the beginning of the study period, higher levels of adulthood stress are related to greater BMI for women but not men. Moreover, women who experienced higher levels of childhood stress gained weight more rapidly throughout the 15-year study period than did women who experienced less childhood stress, but neither childhood nor adulthood stress significantly modified men's BMI trajectories. These findings add to our understanding of how childhood stress a more important driver of long-term BMI increase than adult stress-reverberates throughout the life course to foster cumulative disadvantage in body mass, and how such processes differ for men and women. Results highlight the importance of considering sex-specific social contexts of early childhood in order to design effective clinical programs that prevent or treat overweight and obesity later in life. PMID- 26151393 TI - Altered intensity coding in the salicylate-overdose animal model of tinnitus. AB - Tinnitus is one of the leading disorders of hearing with no effective cure as its pathophysiological mechanisms remain unclear. While the sensitivity to sound is well-known to be affected, exactly how intensity coding per se is altered remains unclear. To address this issue, we used a salicylate-overdose animal model of tinnitus to measure auditory cortical evoked potentials at various stimulus levels, and analyzed on single-trial basis the response strength and its variance for the computation of the lower bound of Fisher information. Based on Fisher information profiles, we compared the precision or efficiency of intensity coding before and after salicylate-treatment. We found that after salicylate treatment, intensity coding was unexpectedly improved, rather than impaired. Also, the improvement varied in a sound-dependent way. The observed changes are likely due to some central compensatory mechanisms that are activated during tinnitus to bring out the full capacity of intensity coding which is expressed only in part under normal conditions. PMID- 26151394 TI - Our changing world: impacts on health and infectious diseases. PMID- 26151395 TI - Development of group IV molecular catalysts for high temperature ethylene-alpha olefin copolymerization reactions. AB - This Account describes our research related to the development of molecular catalysts for solution phase olefin polymerization. Specifically, a series of constrained geometry and nonmetallocene (imino-amido-type) complexes were developed for high temperature olefin polymerization reactions. We have discovered many highly active catalysts that are capable of operating at temperatures above 120 degrees C and producing copolymers with a useful range of molecular weights (from medium to ultrahigh depending on precatalyst identity and polymerization conditions) and alpha-olefin incorporation capability. Constrained geometry catalysts (CGCs) exhibit very high activities and are capable of producing a variety of copolymers including ethylene-propylene and ethylene-1 octene copolymers at high reactor temperatures. Importantly, CGCs have much higher reactivity toward alpha-olefins than classical Ziegler-Natta catalysts, thus allowing for the production of copolymers with any desired level of comonomer. In search of catalysts with improved performance, we discovered 3 amino-substituted indenyl-based CGCs that exhibit the highest activity and produce copolymers with the highest molecular weight within this family of catalysts. Phenanthrenyl-based CGCs were found to be outstanding catalysts for the effective production of high styrene content ethylene-styrene copolymers under industrially relevant conditions. In contrast to CGC ligands, imino-amido type ligands are bidentate and monoionic, leading to the use of trialkyl group IV precatalysts. The thermal instability of imino-amido complexes was addressed by the development of imino-enamido and amidoquinoline complexes, which are not only thermally very robust, but also produce copolymers with higher molecular weights, and exhibit improved alpha-olefin incorporation. Imido-amido and imino-enamido catalysts undergo facile chain transfer reactions with metal alkyls, as evidenced by a sharp decrease in polymer molecular weight when the polymerization reactions were conducted in the presence of diethylzinc, an essential requirement for use in the production of olefin block copolymers via chain shuttling polymerization. Overall, the excellent characteristics of imino-amido-type catalysts, including high catalytic activities and ultrahigh molecular weight capabilities, make them good candidates for high temperature syntheses of block and random ethylene-alpha olefin copolymers. Additionally, trialkyl imino-enamido complexes react quickly with various protic and unsaturated organic fragments, leading to a library of dialkyl precatalysts that, in several instances, resulted in superior catalysts. In conjunction with the development of transition metal catalysts, we also synthesized and evaluated activators for olefin polymerization. We found, for example, that, when conducted in coordinating solvents, the reaction between aluminum alkyls and tris(pentafluorophenyl)borane leads to the exclusive formation of alumenium borates, which are excellent activators for CGC complexes. Additionally, we developed a series of highly effective new activators featuring a very weakly coordinating anion composed of two Lewis acids coordinated to an imidazole fragment. PMID- 26151398 TI - My, How Things Have Changed in Multiple Endocrine Neoplasia Type 2A! PMID- 26151399 TI - Surgical Treatment of Diabetes: Making a Case for a Pragmatic Approach. PMID- 26151400 TI - Corrigenda. PMID- 26151402 TI - Letter to the Editor: RE: Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body. PMID- 26151403 TI - Response to the Letter by Grace F. M., et al. PMID- 26151404 TI - Letter to the Editor: Positive Effect of Estrogen on Islet Cell Could Have Made a Contribution to Better Outcomes in Female Patients With Chronic Pancreatitis Undergoing TP-IAT. PMID- 26151405 TI - Author Response to Letter by Delibasi T., et al. PMID- 26151406 TI - Amplified centrosomes may underlie aggressive disease course in pancreatic ductal adenocarcinoma. AB - Centrosome amplification (CA), the presence of centrosomes that are abnormally numerous or enlarged, is a well-established driver of tumor initiation and progression associated with poor prognosis across a diversity of malignancies. Pancreatic ductal adenocarcinoma (PDAC) carries one of the most dismal prognoses of all cancer types. A majority of these tumors are characterized by numerical and structural centrosomal aberrations, but it is unknown how CA contributes to the disease and patient outcomes. In this study, we sought to determine whether CA was associated with worse clinical outcomes, poor prognostic indicators, markers of epithelial-mesenchymal transition (EMT), and ethnicity in PDAC. We also evaluated whether CA could precipitate more aggressive phenotypes in a panel of cultured PDAC cell lines. Using publicly available microarray data, we found that increased expression of genes whose dysregulation promotes CA was associated with worse overall survival and increased EMT marker expression in PDAC. Quantitative analysis of centrosomal profiles in PDAC cell lines and tissue sections uncovered varying levels of CA, and the expression of CA markers was associated with the expression of EMT markers. We induced CA in PDAC cells and found that CA empowered them with enhanced invasive and migratory capabilities. In addition, we discovered that PDACs from African American (AA) patients exhibited a greater extent of both numerical and structural CA than PDACs from European American (EA) patients. Taken together, these findings suggest that CA may fuel a more aggressive disease course in PDAC patients. PMID- 26151407 TI - In vitro method for prediction of plaque reduction by dentifrice. AB - An in vitro Particle Based Biofilm (PBB) model was developed to enable high throughput screening tests to predict clinical plaque reduction. Multi-species oral biofilms were cultured from pooled stimulated human saliva on continuously colliding hydroxyapatite particles. After three days PBBs were saline washed prior to use in screening tests. Testing involved dosing PBBs for 1min followed by neutralization of test materials and rinsing. PBBs were then assayed for intact biofilm activity measured as ATP. The ranking of commercial dentifrices from most to least reduction of intact biofilm activity was Crest ProHealth Clinical Gum Protection, Crest ProHealth, Colgate Total and Crest Cavity Protection. We demonstrated five advantages of the PBB model: 1) the ATP metric had a linear response over >=1000-fold dynamic range, 2) potential interference with the ATP assay by treatments was easily eliminated by rinsing PBBs with saline, 3) discriminating power was statistically excellent between all treatment comparisons with the negative controls, 4) screening test results were reproducible across four tests, and 5) the screening test produced the same rank order for dentifrices as clinical studies that measured plaque reduction. In addition, 454 pyrosequencing of the PBBs indicated an oral microbial consortium was present. The most prevalent genera were Neisseria, Rothia, Streptococcus, Porphyromonas, Prevotella, Actinomyces, Fusobacterium, Veillonella and Haemophilus. We conclude these in vitro methods offer an efficient, effective and relevant screening tool for reduction of intact biofilm activity by dentifrices. Moreover, dentifrice rankings by the in vitro test method are expected to predict clinical results for plaque reduction. PMID- 26151408 TI - Development of an SNP-based PCR assay for rapid differentiation of a Japanese live vaccine strain from field isolates of Erysipelothrix rhusiopathiae. AB - The differentiation of vaccine from non-vaccine isolates is important for disease control. Based on single nucleotide polymorphisms identified by comparison of the genomes of the Koganei 65-0.15 vaccine strain and a reference strain of Erysipelothrix rhusiopathiae, we developed a PCR assay that can differentiate the vaccine strain from field isolates. PMID- 26151410 TI - Toward a culturally informed rehabilitation treatment model for American Indian/Alaska Native veterans. AB - American Indians and Alaska Natives (AI/AN) have a long tradition of military service, allying with Western forces in North America since the 1700s. It is hardly surprising, therefore, that AI/AN veterans experience higher rates of overall disability and service-related disability than veterans of other races and ethnicities. It is not clear, however, that AI/AN veterans with disabilities are receiving effective, culturally informed rehabilitation services. This article examines the incidence of disability among contemporary AI/AN veterans, considers barriers to effective treatment, and points out model programs tailored to the particular needs of this population, with attention to the historical and cultural context of AI/AN military service. PMID- 26151411 TI - Coumarin heterocyclic derivatives: chemical synthesis and biological activity. AB - This review highlights the broad range of science that has arisen from the synthesis of coumarin-linked and fused heterocycle derivatives. Specific topics include their synthesis and biological activity. PMID- 26151409 TI - Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III. AB - A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy. PMID- 26151412 TI - Scanning Electrochemical Microscopy of Single Spherical Nanoparticles: Theory and Particle Size Evaluation. AB - Experiments at individual metal nanoparticles (NPs) can provide important information about their electrochemical and catalytic properties. The scanning electrochemical microscope (SECM) equipped with a nanometer-sized tip was recently used to image single 10 or 20 nm gold particles and quantitatively investigate electrochemical reactions occurring at their surfaces. In this Article, the theory is developed for SECM current vs distance curves obtained with a disk-shaped tip approaching a comparably sized, surface-bound conductive or insulating spherical NP. The possibility of evaluating the size of a surface bound particle by fitting the experimental current-distance curve to the theory is shown for NPs and tips of different radii. The effects of the NP being partially buried into an insulating layer and the imperfect positioning of the tip with respect to the NP center are considered. The collection efficiency is calculated for redox species generated at the nanoparticle surface and collected at the tip. PMID- 26151413 TI - Thermodynamic approach to the stability of multi-phase systems: application to the Y2O3-Fe system. AB - Oxide-metal systems are important in many practical applications, and they are undergoing extensive study using a wide range of techniques. The most accurate theoretical approaches are based on density functional theory (DFT), which is limited to ~10(2) atoms. Multi-scale approaches, e.g. DFT + Monte Carlo, are often used to model oxide metal systems at the atomic level. These approaches can qualitatively describe the kinetics of some processes but not the overall stability of individual phases. In this article, we propose a thermodynamic approach to study equilibrium in multi-phase systems, which can be sequentially enhanced by considering different defects and microstructures. We estimate the thermodynamic equilibrium by minimization of the free energy of the whole multi phase system using a limited set of defects and microstructural objects for which the properties are calculated by DFT. As an example, we consider Y2O3 + bcc Fe with vacancies in both the Y2O3 and bcc Fe phases, Y substitutions and O interstitials in Fe, Fe impurities, and antisite defects in Y2O3. The output of these calculations is the thermal equilibrium concentration of all the defects for a particular temperature and composition. The results obtained confirmed the high temperature stability of yttria in iron. Model development toward more accurate calculations is discussed. PMID- 26151414 TI - Nanoparticle Adhesion and Mobility in Thin Layers: Nanodiamonds As a Model. AB - Small size and enhanced properties of nanoparticles (NP) are great advantages toward device miniaturization. However, adhesion is essential for the reliability of such NP layer-based devices. In this work, we present some quick tests to investigate the adhesion behavior of the whole NP layer by mimicking several applicative environments: biological buffers and cells, corrosion, and microfabrication processes. This statistic approach evaluates both adhesion and mobility respectively through particle density and layer homogeneity. We chose nanodiamonds (ND) as reference particles because they are spherical and inert and exhibit either positive or negative zeta potential for the same diameter while surfactant-free. Several deposition methods were used to prepare a wide range of ND layers with various densities and size distribution. We found some unexpected results confirming that the deposition method has to be carefully selected according to the targeted application. A selection of the suitable method(s) to prepare ND layers which are resilient in their applicative environment can be done based on these results. However, ND adhesion still remains critical in some conditions and thus requires further improvement. Most important, this study points out that NP adhesion behavior is more complex than simple particle detachment-or not-from the surface. The particles could also reorganize themselves in clusters. We evidenced, in particular, a surprising mobility driven by air/water interfaces during evaporation of water microdroplets. Further comparison with other materials would indicate if the highlighted phenomena could be extended to any nanoparticles layer. PMID- 26151415 TI - A novel endoplasmic reticulum stress-induced apoptosis model using tunicamycin in primary cultured neonatal rat cardiomyocytes. AB - Endoplasmic reticulum (ER) stress is key in the development of cardiovascular diseases. However, there is a lack of a systemic ER stress-induced cardiomyocyte apoptosis model. In the present study, primary cultured neonatal rat cardiomyocytes were exposed to tunicamycin. Cell viability was determined by an MTT assay, and cell damage was detected by a lactose dehydrogenase assay. Flow cytometry was used and the activity of caspase-3 was analyzed in order to measure apoptosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to examine the expression of glucose-regulated protein 78-kDa (GRP78) and C/EBP homologous protein (CHOP). As a result, tunicamycin significantly increased cardiomyocyte injury, which occurred in a time- and concentration-dependent manner. In addition, tunicamycin treatment resulted in apoptosis of cardiomyocytes. Molecularly, tunicamycin (100 ng/ml) increased the levels of GRP78 and CHOP 6 h after administration. In addition, GRP78 and CHOP reached maximum mRNA and protein levels 24 h after administration. In conclusion, the results implicate that the tunicamycin-induced ER stress-induced apoptotic model was successfully constructed in cultured neonatal rat cardiomyocytes. A 100 ng/ml concentration of tunicamycin was selected, and MTT, LDH release and flow cytometry assay was at 72 h. In addition, GRP78 and GRP94 were detected 24 h following administration. The results of the present study indicate a novel experimental basis for the investigation of ERS-induced cardiac apoptosis. PMID- 26151417 TI - Domino Process Achieves Site-Selective Peptide Modification with High Optical Purity. Applications to Chain Diversification and Peptide Ligation. AB - The development of peptide libraries by site-selective modification of a few parent peptides would save valuable time and materials in discovery processes but still is a difficult synthetic challenge. Herein, we introduce natural hydroxyproline as a convertible unit for the production of a variety of optically pure amino acids, including expensive N-alkyl amino acids, homoserine lactones, and Agl lactams, and to achieve the mild, efficient, and site-selective modification of peptides. A domino process is used to cleave the customizable Hyp unit under mild, metal-free conditions. Both terminal and internal positions can be modified, and similar customizable units can be differentiated. The resulting products possess two reactive chains which can be manipulated independently. The versatility and scope of this process is highlighted by its application to the ligation of two peptide chains, and the generation of peptides with several chains and peptides with conformational restrictions. PMID- 26151416 TI - Cardiac fibroblasts as sentinel cells in cardiac tissue: Receptors, signaling pathways and cellular functions. AB - Cardiac fibroblasts (CF) not only modulate extracellular matrix (ECM) proteins homeostasis, but also respond to chemical and mechanical signals. CF express a variety of receptors through which they modulate the proliferation/cell death, autophagy, adhesion, migration, turnover of ECM, expression of cytokines, chemokines, growth factors and differentiation into cardiac myofibroblasts (CMF). Differentiation of CF to CMF involves changes in the expression levels of various receptors, as well as, changes in cell phenotype and their associated functions. CF and CMF express the beta2-adrenergic receptor, and its stimulation activates PKA and EPAC proteins, which differentially modulate the CF and CMF functions mentioned above. CF and CMF also express different levels of Angiotensin II receptors, in particular, AT1R activation increases collagen synthesis and cell proliferation, but its overexpression activates apoptosis. CF and CMF express different levels of B1 and B2 kinin receptors, whose stimulation by their respective agonists activates common signaling transduction pathways that decrease the synthesis and secretion of collagen through nitric oxide and prostacyclin I2 secretion. Besides these classical functions, CF can also participate in the inflammatory response of cardiac repair, through the expression of receptors commonly associated to immune cells such as Toll like receptor 4, NLRP3 and interferon receptor. The activation by their respective agonists modulates the cellular functions already described and the release of cytokines and chemokines. Thus, CF and CMF act as sentinel cells responding to a plethora of stimulus, modifying their own behavior, and that of neighboring cells. PMID- 26151418 TI - Addendum to "WSTF does it all: a multifunctional protein in transcription, repair, and replication". PMID- 26151419 TI - THE RELATIONSHIP BETWEEN SERUM 25-HYDROXYVITAMIN D AND GLUCOSE HOMEOSTASIS IN OBESE CHILDREN AND ADOLESCENTS IN ZHEJIANG, CHINA. AB - OBJECTIVE: Evidence of the association between vitamin D, insulin resistance, and oral disposition index (oDI) in obese children and adolescents is limited. To fill this research gap, we measured serum 25-hydroxyvitamin D (25[OH]D) levels in obese children and analyzed the relationship between serum 25(OH)D levels and glucose homeostasis. METHODS: Altogether, 348 obese and 445 nonobese children and adolescents (age, 6 to 16 years) were enrolled in this study. Obese children were divided into 4 subgroups: normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG and IGT (IFG+IGT) according to oral glucose tolerance test results. We measured serum 25(OH)D levels and calculated the homeostasis model assessment (HOMA) of insulin resistance (IR), the whole-body insulin sensitivity index (WBISI), and the disposition index. RESULTS: The levels of 25(OH)D in the obese group were significantly lower than in the nonobese group; serum 25(OH)D level in the NGT subgroup was higher than those of the other 3 subgroups, and it was significantly inversely correlated with logHOMA-IR (r = -0.090; P = .045) and positively correlated with logWBISI and logHOMA-oDI (r = 0.091, P = .049; and r = 0.108, P = .046, respectively). Obese patients with vitamin D deficiency thus have a significantly higher risk of disturbances in glucose metabolism. CONCLUSION: 25(OH)D deficiency or insufficiency is quite common in obese children and adolescents in Zhejiang, China. Obese patients with 25(OH)D deficiency (<30 nmol/L) are shown to be at higher risk for abnormal glucose metabolism. PMID- 26151420 TI - ZOLEDRONIC ACID THERAPY OF PATIENTS WITH PAGET DISEASE OF BONE RESISTANT TO OR WITH UNSUSTAINED REMISSION FOLLOWING PRIOR BISPHOSPHONATE THERAPY. AB - OBJECTIVE: To evaluate the effect of zoledronic acid (ZA) in patients with Paget disease (PD) who had not had a biochemical remission with prior bisphosphonate therapy or had a remission <=12 months. METHODS: The effects of ZA therapy were studied in 14 patients aged 54 to 90. Serum alkaline phosphatase (ALP) levels were elevated to at least 40% above the normal reference range, and glomerular filtration rates (GFRs) were >=40 mL/minute. ZA (5 mg) was infused over 15 minutes. ALP and urine N-telopeptide/creatinine (NTx/Cr) were obtained before therapy and at 3, 6, 9, and 12 months, and thereafter at 4-month intervals. RESULTS: At baseline, ALP ranged from 141 to 1,009 U/L. In 13 patients, ALP fell to normal following ZA administration. Remissions occurred in 9 patients who had not previously had a remission. Remissions varied from 12 to 60 months and were more prolonged in 4 patients with prior remissions <=12 months. ZA failed to induce a remission in 1 patient. Ten to 12 days after therapy in 3 asymptomatic patients, serum calcium levels fell to 7.9, 8, and 8.3 mg/dL. Other than flu-like symptoms in 3 patients after ZA infusion, there were no other adverse effects. CONCLUSION: Therapy with ZA induced remissions in 13/14 patients and induced more prolonged remissions in patients who previously had remissions <=12 months. The lack of remission in 1 patient despite 2 courses of therapy is evidence of a continuing therapeutic challenge for some patients with a more resistant form of PD. PMID- 26151421 TI - COMPARISON OF VITAMIN D REPLACEMENT STRATEGIES WITH HIGH-DOSE INTRAMUSCULAR OR ORAL CHOLECALCIFEROL: A PROSPECTIVE INTERVENTION STUDY. AB - OBJECTIVE: To ascertain the frequency of correction of vitamin D deficiency (VDD) with single or multiple doses of oral (p.o.) and intramuscular (i.m.) administration of 2 high-dose preparations of vitamin D3 (VD3). METHODS: This was a prospective intervention study conducted in an ambulatory care setting. One hundred participants with VDD (25-hydroxy vitamin D [25-OHD] <20 ng/mL) were randomized to receive a dose of 600,000 or 200,000 IU of VD3 via a p.o. or i.m. route. The main outcome measure was serum 25-OHD levels at 2, 4, and 6 months after the intervention. The same dose was repeated in participants if 25-OHD remained <30 ng/mL at 2 and 4 months. RESULTS: At 2 months, VDD was corrected in 93.8% of participants in Group 1 (600,000 IU i.m.); 83.3% in Group 2 (600,000 IU p.o.), 87.5% in Group 3 (200,000 IU i.m.), and 70.6% in Group 4 (200,000 IU p.o.). The mean changes from baseline in vitamin D levels at 2 months were 29.6 +/- 13.7, 19.8 +/- 12.3, 18.3 +/- 10.6, and 13.7 +/- 7.8 ng/mL in Groups 1, 2, 3, and 4, respectively. The mean levels remained significantly higher from baseline in all groups at all time points during the 6 months of observation. The mean 25 OHD level achieved in Group 1 was significantly higher than all other groups at 6 months. CONCLUSION: Two months after the intervention, VDD was corrected in more than 70% of participants with a single dose of either 600,000 or 200,000 IU given p.o. or i.m. PMID- 26151422 TI - POSITIVE TEST FOR ANTITHYROGLOBULIN ANTIBODIES DUE TO ADMINISTRATION OF IMMUNOGLOBULIN REPLACEMENT THERAPY IN A PATIENT WITH THYROID CANCER. AB - OBJECTIVE: Thyroglobulin (Tg) is used as a tumor marker to monitor differentiated thyroid cancer progression and recurrence. However, Tg measured by standard immunoassay (IMA) is not a reliable marker in the presence of anti-Tg antibodies (TgAbs) due to interference that may result in either false-positive or false negative results. TgAbs levels can be high due to thyroid cancer and also exogenous immunoglobulin (Ig) administration, thus making it difficult to identify differentiated thyroid cancer recurrence. METHODS: We present an example of elevated TgAbs due to subcutaneous Ig (SCIg) administration in a patient with thyroid cancer. RESULTS: A 57-year-old male was diagnosed with stage I papillary thyroid cancer (PTC). His TgAbs were negative prior to the diagnosis of thyroid cancer and became positive after thyroidectomy and radioactive iodine administration. A detailed work-up including a whole body scan did not reveal recurrent disease. He had been diagnosed with common variable immune deficiency (CVID) and dermatomyositis at the age of 50 and was started on immunoglobulin (Ig) replacement therapy shortly after diagnosis. His Tg was negative when assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Therefore, elevated TgAb titers were attributed to concomitant SCIg treatment. We also demonstrated that SCIg treatment had TgAb activity that was removed by protein A column treatment. Dilutions of SCIg medication also caused positive IgG serologies for cytomegalovirus and herpes simplex, measles, mumps, rubella, and varicella zoster viruses. CONCLUSION: An exogenous source of TgAbs from SCIg led to extensive imaging work-up to assess for PTC recurrence. LC-MS/MS is a conceptually attractive approach to overcome TgAb interference with Tg IMA measurement. PMID- 26151423 TI - RELATIONSHIP OF ADIPOKINES AND PROINFLAMMATORY CYTOKINES AMONG ASIAN INDIANS WITH OBESITY AND YOUTH ONSET TYPE 2 DIABETES. AB - OBJECTIVE: It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth onset type 2 diabetes mellitus (T2DM-Y). METHODS: We recruited individuals with T2DM-Y (age at onset <25 years) and age-matched normal glucose tolerance (NGT) subjects. Participants were further classified using Asia-Pacific body mass index cut-points for obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and monocyte chemotactic protein-1 [MCP-1]) across groups. RESULTS: Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 MUg/mL, P<.01), and higher leptin (3.6 vs. 5.4, 5.7, 7.9 MUg/mL, P<.001) and MCP 1 (186 vs. 272, 340, 473 pg/mL, P<.001) respectively. However, TNF-alpha levels were higher only among nonobese T2DM-Y (112 pg/mL) and obese T2DM-Y (141 pg/mL, P<.01 for each). After adjusting for age, sex, waist, hypertension, homeostatic model assessment of insulin resistance (HOMA-IR), serum cholesterol, triglycerides, and family history of diabetes, adiponectin was associated with 33% and 41% lower odds of being nonobese T2DM and obese T2DM, respectively. However, adjusted for same factors, leptin, TNF-alpha, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM. CONCLUSION: In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals. PMID- 26151424 TI - A SIMPLE INTERVENTION RAISED RESIDENT-PHYSICIAN WILLINGNESS TO ASSIST TRANSGENDER PATIENTS SEEKING HORMONE THERAPY. AB - OBJECTIVE: Lack of physician knowledge about transgender medicine is a barrier to care. An intervention with medical students changed attitudes about providing transgender medical care, but it is unknown whether at the level of postgraduate education an intervention could have a similar effect. We conducted such an intervention with resident-physicians. METHODS: An intervention on transgender medicine covering the durability of gender identity and hormonal treatment regimens was added to the curriculum for residents. An anonymous survey assessed the residents' knowledge and willingness to assist with hormonal therapy before and after the lecture. RESULTS: The percent of residents who agreed that they felt sufficiently knowledgeable to assist with hormonal therapy for a female-to male patient increased significantly, from 5% before to 76% following the lecture (chi(2), 24.7; degrees of freedom, 1; P<.001). The percent of residents who reported that they felt sufficiently knowledgeable to assist with hormonal therapy for a male-to-female patient increased significantly, from 5% before to 71% following the lecture (chi(2), 24.0; degrees of freedom, 1; P<.001). The intervention increased resident knowledge about hormonal therapy for hypogonadal men (chi(2), 11.4; degrees of freedom, 1; P<.001) and women (chi(2), 9.4; degrees of freedom, 1; P = .002). The intervention made more residents agree that gender identity has a biologic basis that remains constant (P<.001) and that hormonal and surgical therapies should be offered (P = .047). CONCLUSION: The lecture significantly increased residents' knowledge and willingness to assist with hormonal therapy for transgender patients. PMID- 26151425 TI - Hindered rotational physisorption states of H2 on Ag(111) surfaces. AB - We have investigated the physisorption states of H2 on Ag(111) surfaces. To clarify the accurate adsorption properties of H2 on Ag(111), we performed first principles calculations based on spin-polarized density functional theory (DFT) with the semiempirical DFT-D2 method and the newly-developed exchange functional with the non-local correlation functional vdW-DF2 (rev-vdW-DF2). We constructed exhaustive potential energy surfaces, and revealed that non-negligible out-of plane potential anisotropy with a perpendicular orientation preference exists even for H2 physisorption on planar Ag(111), as predicted by previous results of resonance-enhanced multiphoton ionization spectroscopy and temperature-programmed desorption experiments. Therefore, the molecular rotational ground states of ortho-H2 split into two energy levels in the anisotropic potential. The obtained adsorption energy and the number of bound states, including the zero-point energies and the rotational energy shift, agree with diffractive and rotationally mediated selective adsorption scattering resonance measurements. The origin of the potential anisotropy on Ag(111) is a combination of the London dispersion interaction and the virtual transition of the metal electron to the unoccupied molecular state. PMID- 26151426 TI - Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis. AB - An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct. PMID- 26151428 TI - Visible Light-Mediated Ullmann-Type C-N Coupling Reactions of Carbazole Derivatives and Aryl Iodides. AB - The combined use of an iridium-based photocatalyst and a copper salt under blue light emitting diode irradiation enables the Ullmann-type C-N cross-coupling reaction between carbazole derivatives and aryl iodides to proceed under mild conditions. PMID- 26151427 TI - MicroRNA-21 regulates the expression of BTG2 in HepG2 liver cancer cells. AB - B-cell translocation gene 2 (BTG2) is a tumor suppressor gene, which belongs to the anti-proliferation gene family. Our previous study demonstrated that microRNA (miR)-21 and the expression of BTG2 were negatively correlated during hepatocarcinogenesis. The aim of the present study was to investigate the effects of miR-21 on the growth and progression of liver cancer cells, and to determine the underlying mechanism. A luciferase reporter assay was used to demonstrate that the BTG2 gene was a direct target of miR-21. In addition, the effects of miR 21 on cell growth and gene expression in HepG2 human hepatocellular carcinoma (HCC) cells were analyzed using reverse transcription-quantitative polymerase chain reaction, western blotting, an MTT assay, flow cytometry, a Transwell invasion assay and a wound healing assay. The expression levels of miR-21 in the HepG2 cells were significantly higher, compared with those in L02 normal liver cells. The expression levels of BTG2 in liver cancer cell lines (HepG2 and Huh7) were significantly lower, compared with that in the L02 cells. These results suggested that BTG2 was the direct target gene of miR-21. The protein expression levels of BTG2 were inhibited by high expression levels of miR-21, and increased by inhibition of the expression of miR-21 in the HepG2 cells. Inhibition of miR 21 reduced cell proliferation and invasion, and increased the rate of apoptosis in the HepG2 cells. These results indicated that miR-21 regulates cell proliferation, invasion, migration and apoptosis in HepG2 cells, which may be associated with its effects on the expression of BTG2. The results of the present study may provide a basis for targeting the miR-21/BTG2 interaction for the treatment of HCC. PMID- 26151429 TI - Chromofungin, CgA47-66-derived peptide, produces basal cardiac effects and postconditioning cardioprotective action during ischemia/reperfusion injury. AB - Endogenous chromogranin A (CgA)-derived peptides are secreted by nervous, endocrine and immune cells. Chromofungin (Chr: CgA47-66) is one of these peptides that display antimicrobial activities and activate neutrophils, with important implications in inflammation and innate immunity. The aim of the present study is to examine the effects of Chr on isolated and Langendorff perfused rat hearts. The study was performed by using the isolated and Langendorff perfused rat hearts, Elisa assay and real-time PCR. We found that, under basal conditions, increasing doses (11-165nM) of Chr induced negative inotropic effects without changing coronary pressure. This action was mediated by the AKT/eNOS/cGMP/PKG pathway. We also found that Chr acted as a postconditioning (PostC) agent against ischemia/reperfusion (I/R) damages, reducing infarct size and LDH level. Cardioprotection involved PI3K, RISK pathway, MitoKATP and miRNA-21. We suggest that Chr directly affects heart performance, protects against I/R myocardial injuries through the activation of prosurvival kinases. Results may propose Chr as a new physiological neuroendocrine modulator able to prevent heart dysfunctions, also encouraging the clarification of its clinical potential. PMID- 26151431 TI - Crystal growth, spectral, optical, laser damage, photoconductivity and dielectric properties of semiorganic L-cystine hydrochloride single crystal. AB - The semiorganic single crystals of l-cystine hydrochloride have been grown by slow evaporation solution growth technique at 40 degrees C. The grown crystals were subjected to single crystal XRD, FTIR, optical absorbance, laser damage threshold, photoluminescence, photoconductivity and dielectric studies. Single crystal XRD studies reveal that the crystal belongs to monoclinic system with space group C2 and the lattice parameters are a=18.63 (A), b=5.28 (A), c=7.26 (A), alpha=90 degrees , beta=103.70 degrees , gamma=90 degrees and V=696 (A(3)). FTIR spectroscopy confirms that a band at 1731 cm(-1) represents characteristic of alpha-amino acid hydrochlorides. The UV-Vis-NIR absorption spectrum was analyzed and the optical band gap energy was found to be 3.8eV. The crystal exhibits sharp emission peak at 388 nm. The thermal characteristics of crystals were studied by TG-DTA, which indicate that there is no weight loss up to 201 degrees C. Surface laser damage threshold value of title compound was estimated using high power Q-switched Nd:YAG laser operating at 1064 nm. Dielectric and photoconductivity studies were also carried out for the grown crystals. PMID- 26151430 TI - Rapid kinetics of dehalogenation promoted by iodotyrosine deiodinase from human thyroid. AB - Reductive dehalogenation such as that catalyzed by iodotyrosine deiodinase (IYD) is highly unusual in aerobic organisms but necessary for iodide salvage from iodotyrosine generated during thyroxine biosynthesis. Equally unusual is the dependence of this process on flavin. Rapid kinetics have now been used to define the basic processes involved in IYD catalysis. Time-dependent quenching of flavin fluorescence was used to monitor halotyrosine association to IYD. The substrates chloro-, bromo-, and iodotyrosine bound with similar rate constants (kon) ranging from 1.3 * 10(6) to 1.9 * 10(6) M(-1) s(-1). Only the inert substrate analogue fluorotyrosine exhibited a significantly (5-fold) slower kon (0.3 * 10(6) M(-1) s(-1)). All data fit a standard two-state model and indicated that no intermediate complex accumulated during closure of the active site lid induced by substrate. Subsequent halide elimination does not appear to limit reactions of bromo- and iodotyrosine since both fully oxidized the reduced enzyme with nearly equivalent second-order rate constants (7.3 * 10(3) and 8.6 * 10(3) M(-1) s(-1), respectively) despite the differing strength of their carbon-halogen bonds. In contrast to these substrates, chlorotyrosine reacted with the reduced enzyme approximately 20-fold more slowly and revealed a spectral intermediate that formed at approximately the same rate as the bromo- and iodotyrosine reactions. PMID- 26151432 TI - Correlation between 195Pt chemical shifts and the electronic transitions among d orbitals in pincer NCN Pt(II) complexes: A theoretical study and application of Ramsey's equation. AB - The chemical potentials for two series of [PtCl(NCN-Z-4)] (NCN=2,6 bis[(dimethylamino)methyl]phenyl, Z=H, CHO, COOH, NH2, OH, NO2, SiMe3, I, t-Bu) and [PtCl(NCN-4-CHN-C6H4-Z'-4')] (Z'=NMe2, Me, H, Cl, CN) were calculated. The energies of platinum d orbitals were calculated by NBO analysis. Good correlations were obtained between (195)Pt chemical shifts and the spectral parameters obtained from the energies of electronic transitions between Pt d orbitals in these complexes. The correlations between (195)Pt chemical shifts and the chemical potentials were also good. The correlations were discussed based on Ramsey's equation. PMID- 26151433 TI - The structure and photophysics of di-iodo-zinc(II) complexes of long alkyl chain substituted imidazolyl motif of arylazoimidazoles and the DFT computation. AB - Distorted tetrahedral structure of [Zn(Haai-C10H21)2I2] (Haai-C10H21, 1-decayl-2 (arylazo)imidazole) has been supported by single crystal X-ray diffraction study. The structures of other complexes, [Zn(Raai-CnH2n+1)2I2] (n=10, 12, 14, 16, 18, 20, 22) have been determined by spectroscopic data (FT-IR, UV-vis, (1)H NMR). The complexes show light induced photoisomerisation, E-to-Z (trans-to-cis) of coordinated, Raai-CnH2n+1. The Z-to-E (cis-to-trans) isomerisation is also carried out by thermal activation route. The quantum yields of the E->Z progression (phiE->Z) of the complexes are less than that of free ligand, which could be due to increase in molar mass and molar volume of the complexes than that of free ligands. The activation energy (Ea) of Z->E isomerisation of the complexes is is less than that of free ligands. This observation is also consistent with femtosecond transient absorption results which suggests that the E(trans)->Z(cis) isomerization occurs through the motion of pendant NNAr of the molecule. The temporal profiles of free ligand shows three decay processes corresponds to 0.24ps (S2 state) and subsequent decay, 0.85ps of the S1 state and finally 5ps to the hot ground state at 500nm. The complexes also show three decay periods approximately at 0.25ps, 1.3ps and 13ps. The spectral property and photochromic efficiency have been explained by DFT computation of optimized geometry of the complexes. PMID- 26151434 TI - Speciation and site occupancy of uranium in strontium orthosilicate by photoluminescence and X-ray absorption spectroscopy: A combined experimental and theoretical approach. AB - Identifying the oxidation state and coordination geometry of radioactive element like uranium is important to fully understand its toxicology and other harmful effect in environment. Strontium orthosilicate is taken as a model compound for that. Strontium silicate doped with 1.0 mol% of U has been synthesized using sol gel method and characterized using X-ray diffraction (XRD), time resolved fluorescence spectroscopy (TRFS) and extended X-ray absorption fine structure (EXAFS). Uranium exhibits multiple oxidation state and each one of them is having characteristics luminescence is an interesting dopant from structural point of view. TRFS is used to investigate the oxidation state and coordination behavior of uranium in Sr2SiO4. From TRFS measurement it was observed that uranium stabilizes in +6 oxidation state in the form of uranyl ion. Based on luminescence lifetime and EXAFS studies it was inferred that uranyl is stabilized on both 9- and 10-coordinated strontium polyhedra but majority occupies relatively asymmetric 9-coordinated Sr sites. This is further confirmed using theoretical measurement. PMID- 26151435 TI - Raman spectroscopic study of the Chromobacterium violaceum pigment violacein using multiwavelength excitation and DFT calculations. AB - Violacein is a bisindole pigment occurring as a biosynthetic product of Chromobacterium violaceum and Janthinobacterium lividum. It has some structural similarities to the cyanobacterial UV-protective pigment scytonemin, which has been the subject of comprehensive spectroscopic and structural studies. A detailed experimental Raman spectroscopic study with visible and near-infrared excitation of violacein produced by C. violaceum has been undertaken and supported using theoretical DFT calculations. Raman spectra with 514 and 785 nm excitation of cultivated cells as well as extracts and Gaussian (B3LYP/6 311++G(d,p)) calculations with proposed molecular vibrational assignments are reported here. PMID- 26151436 TI - R0 Structural parameters, conformational, vibrational studies and ab initio calculations of cyanocyclopentane. AB - The infrared and Raman spectra (3100-50 cm(-1)) of the gas, liquid or solution, and solid have been recorded of cyanocyclopentane, c-C5H9CN. Variable temperature (-60 to -100 degrees C) studies of the infrared spectra (3100-400cm(-1)) of the sample dissolved in liquid xenon have been carried out. From these data, both the envelope-equatorial (Eq) and Ax conformers have been identified and their relative stabilities obtained. The enthalpy difference has been determined to be 55 +/- 12 cm(-1) (0.66 +/- 0.14 kJ/mol) with the Eq conformer the more stable form. The percentage of the Ax conformer is estimated to be 45+/-1% at ambient temperature. The conformational stabilities have been predicted from ab initio calculations by utilizing several different basis sets up to aug-cc-pVTZ from both MP2(full) and density functional theory calculations by the B3LYP method. Vibrational assignments have been made for the observed bands for both conformers with initial predictions by MP2(full)/6-31G(d) ab initio calculations to obtain harmonic force constants, wavenumbers, infrared intensities, Raman activities and depolarization ratios for both conformers. The r0 structural parameter values for the Eq[Ax] form are; for the heavy atom distances (A): CN=1.160 [1.160] (3); Calpha-C=1.463 [1.463] (3); Calpha-Cbeta, Cbeta'=1.543 [1.545] (3); Cbeta-Cgamma, Cgamma'=1.540 [1.541] (3); Cgamma-Cgamma'=1.552 [1.553] (3) and angles ( degrees ): ?Calpha-CN=179.0 [178.9] (5); ?CbetaCalpha-C=113.1 [110.1] (5); ?CbetaCalphaCbeta'=103.0 [102.1] (5); ?CalphaCbetaCgamma=104.1 [104.8] (5); ?CbetaCgammaCgamma'=106.3 [106.0] (5). The results are discussed and compared to the corresponding properties of some related molecules. PMID- 26151437 TI - Synthesis, computational and spectroscopic analysis on (E)-(4-(2-(benzo[d]thiazol 2-yl)hydrazono)-3-methyl-2,6-diphenylpiperidine-1-yl)(phenyl)methanone using DFT approach. AB - (E)-(4-(2-(benzo[d]thiazol-2-yl)hydrazono)-3-methyl-2,6-diphenylpiperidin-1 yl)(phenyl)methanone [EPHDPM] and its derivatives were synthesized and characterized by FT-IR, (1)H NMR, (13)C NMR and elemental analysis. The target compound [EPHDPM] was computed using density functional theory (DFT) method. The ground-state molecular geometry and vibrational frequencies were calculated by using B3LYP/6-31G (d,p) level of theory. The experimentally observed FT-IR and FT Raman bands were assigned to different normal modes of the molecule. The stability and charge delocalization of the molecule were also studied by natural bond orbital (NBO) analysis. The HOMO-LUMO energies describe the charge transfer takes place within the molecule. Molecular electrostatic potential has been analyzed. The reported EPHDPM molecule used as a potential NLO material since it has high MUbeta0 value. Thermodynamic parameter like entropy and enthalpy are calculated and these values are increased with increasing the temperature due to the enhancement of vibrational intensities. PMID- 26151438 TI - The influence of seat heights and foot placement positions on postural control in children with cerebral palsy during a sit-to-stand task. AB - This paper aimed to analyze, from both a kinetic and kinematic perspective, the postural control of children with cerebral palsy (CP) able to independently perform the sit-to-stand (STS) task (ICP) and children who needed support (SCP) typically developing children during the STS; and also investigate the influence of seats heights and foot placement positions on postural control of these children. Fourteen children with CP and fourteen typically developing controls were recruited. Based on the Gross Motor Function Classification System (GMFCS) the children with CP were divided into ICP (level I) and SCP (levels II and III). Balance was assessed using the Pediatric Balance Scale. Motor function was rated using the GMFCS. Kinematic and kinetic data were recorded and analyzed during the STS task at two different seat heights and foot placement positions. The SCP exhibited significantly less balance according to the PBS and smaller displacement of their center of pressure (COP) in anteroposterior (COPAP) and mediolateral (COPML) direction relative to the other two groups. ICP demonstrated significant greater in the COPML displacement than the other groups. Children with CP required more time to complete the STS than controls. Those in the SCP group had lower linear displacement of the shoulder and knee than others during the STS task. During the high bench condition, the linear displacements of the shoulder and knee were reduced also. We conclude that the SCP has less COPAP and COPML oscillation, what means the better postural control during STS than the other two groups, which may be related to the support provided. The ICP exhibited greater COPML oscillations than controls, suggesting that they utilized different strategies in the frontal plane during the STS task. The seat height and foot placement did not influence postural control in children with CP, at least in terms of kinetic parameters. Seat height influenced the kinematic variables, with a high bench reducing linear displacement of the shoulder (vertical and horizontal) and knee (vertical) both in children with CP and control children. PMID- 26151439 TI - Surveying parental experiences of receiving a diagnosis of developmental coordination disorder (DCD). AB - Receiving a diagnosis of a developmental disorder has a major impact on an individual and their family. However, little is known about parental experiences of having a child diagnosed with developmental coordination disorder (DCD). In this study, 228 parents completed an online survey about their experiences of obtaining a diagnosis of DCD for their child in the United Kingdom. Results demonstrated that, on average, a diagnosis was confirmed two and a half years after parents initially sought professional help in relation to their child's motor difficulties. Satisfaction with the overall diagnostic process was mixed: 45% of parents were dissatisfied (26%=very dissatisfied, 19%=quite dissatisfied) and 39% were satisfied (16%=very satisfied, 23%=quite satisfied). Four factors were predictive of parental satisfaction with the overall diagnostic process: the stress of the diagnostic process; the manner of the diagnosing professional; satisfaction with post-diagnostic support; and the time taken to get a diagnosis. Post-diagnostic provision was the area in which parents reported most dissatisfaction; an unsurprising finding given that 43% of parents were not offered any practical help or support during the diagnostic process or in follow up appointments (although there was an indication that this was improving). Based on these findings (as well as previous research), we propose three key areas in which improvements in the diagnostic process for DCD are needed: (1) greater awareness about DCD in order to facilitate earlier recognition; (2) implementation of clear referral pathways, to reduce the time taken to receive a diagnosis; and (3) increased post-diagnostic support within health and educational systems. PMID- 26151440 TI - A controlled trial of the SibworkS group program for siblings of children with special needs. AB - Siblings of children with a disability are an at risk group for emotional and behavioral problems. This study evaluated an intervention to promote the emotional and behavioral functioning of siblings of children with disabilities and chronic health conditions. SibworkS is a six-week manual-based, cognitive behavioral group support program focussed on strengthening siblings' perceived social support, self-esteem, problem-solving skills, adaptive coping behaviors and positive sibling relationships. Fifty-six children aged 7-12 were allocated to either the SibworkS program (n=30) or waitlist control (n=26) in alternating sequence. The primary outcome was siblings' emotional and behavioral functioning. Additional outcomes were self-esteem, perceived social support, the sibling relationship and coping behaviors. Siblings were followed-up immediately after the intervention and at 3-months. Siblings participating in the SibworkS intervention were reported to have fewer emotional and behavioral difficulties than siblings in the control group immediately following the intervention and at the 3-month follow-up. Participation in SibworkS was associated with fewer emotional and behavioral difficulties for siblings. Implications for practice and future research include recommendations for improving program participation. PMID- 26151441 TI - A general number-to-space mapping deficit in developmental dyscalculia. AB - Previous research on developmental dyscalculia (DD) suggested that deficits in the number line estimation task are related to a failure to represent number magnitude linearly. This conclusion was derived from the observation of logarithmically shaped estimation patterns. However, recent research questioned this idea of an isomorphic relationship between estimation patterns and number magnitude representation. In the present study, we evaluated an alternative hypothesis: impairments in the number line estimation task are due to a general deficit in mapping numbers onto space. Adults with DD and a matched control group had to learn linear and non-linear layouts of the number line via feedback. Afterwards, we assessed their performance how well they learnt the new number space mappings. We found irrespective of the layouts worse performance of adults with DD. Additionally, in case of the linear layout, we observed that their performance did not differ from controls near reference points, but that differences between groups increased as the distance to reference point increased. We conclude that worse performance of adults with DD in the number line task might be due a deficit in mapping numbers onto space which can be partly overcome relying on reference points. PMID- 26151442 TI - Three physiological responses in fathers and non-fathers' to vocalizations of typically developing infants and infants with Autism Spectrum Disorder. AB - Children with ASD, even before receiving a formal diagnosis, express atypical patterns of distress vocalizations (namely, episodes of crying). Their cries have higher fundamental frequencies, shorter inter-bout pauses, and fewer utterances. Cries of children with ASD are also perceived differently from other cries, and these perceptual differences may alter parent-infant interaction. This study assessed multiple physiological responses in fathers and non-fathers to atypical distress vocalizations (cries of children with ASD), acoustically matched typical distress vocalizations (cries of typically developing children), and positive vocalizations (laughter of typically developing children). The experimental procedures were designed to measure how components of the autonomic nervous system respond to typical and atypical infant vocalizations. Three convergent methodologies (Galvanic Skin Response-GSR; cardiac dynamics via Inter-Beat Interval-IBI; right hand temperature change-RHTC) were performed on two groups with contrasting caregiving experience: fathers of typically developing children (n=10) and non-fathers (n=10). Inferential statistical analysis compared the two groups (fathers, non-fathers) and three stimulus types (ASD cry, typical cry, laughter) for the three measures (GSR, IBI, RHTC). Both fathers and non-fathers showed greater negative responses (increased GSR) to ASD cries compared to typical cries and laughter. Fathers showed higher IBI and greater temperature increases (RHTC) than non-fathers while listening to typical and atypical cries. Fathers and non-fathers showed more emotional arousal mediated by sympathetic activation while listening to cries of children with ASD. Fathers were calmer and acted more promptly than non-fathers while listening to typical cries, perhaps because the fathers had more experience in caring for crying infants. These findings point to similarities and differences in fathers' and non-fathers' physiological responsiveness to cries of children with ASD and might guide specific intervention programs for parents of children at risk of ASD. PMID- 26151443 TI - Validity and reliability of the Medical Outcomes Study Short-Form Health Survey version 2 (SF-12v2) among adults with autism. AB - BACKGROUND: The purpose of the study was to assess the validity and reliability of the Medical Outcomes Study Short Form-12 version 2 (SF-12v2) instrument among adults with autism. METHODS: Study data was collected using a cross-sectional online survey of adults with autism enrolled with the Interactive Autism Network (N=291). Factorial validity was assessed using confirmatory factor analysis technique. Item-scale correlations were examined for convergent validity. Known groups validity was assessed by examining the variation in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores by autism severity. Cronbach's alpha was determined for internal consistency reliability. Floor and ceiling effects were also assessed. RESULTS: A two-factor model with correlated error terms was found to have a good fit. The PCS scale strongly correlated with the underlying items representing the scale. The MCS scale had strong to moderate correlation with its underlying items. For known-groups validity, the MCS score varied as expected with lower score observed among adults with high severity as compared to low severity; however, PCS score varied inversely. Internal consistent reliability of the SF-12v2 was good, and there were no floor and ceiling effects. CONCLUSIONS: Except for known-groups validity, all other psychometric indicators performed well for the SF-12v2. PMID- 26151444 TI - Effective delivery of a rationally designed intracellular peptide drug with gold nanoparticle-peptide hybrids. AB - A novel gold nanoparticle-peptide hybrid strategy was developed to intracellularly deliver a potent PKCdelta inhibitor peptide for the treatment of acute lung injury. The gold nanoparticle-peptide hybrids showed good stability with high uptake, and demonstrated in vitro and in vivo efficacy. Our formulation strategy shows great promise in intracellular delivery of peptides. PMID- 26151445 TI - Natural nitric oxide (NO) inhibitors from the rhizomes of Curcuma phaeocaulis. AB - An exploration we carried out for isolating nitric oxide (NO) inhibitors from the rhizomes of Curcuma phaeocaulis afforded one new salvialane-type sesquiterpene, phasalvione (1), two novel nor-sesquiterpenes, phaeocaudione (2) and phaeocauone (3), one aromatic acid 3-methyl-4-(3-oxo-butyl)-benzoic acid (4), two gamma elemene-type sesquiterpenes, 8beta(H)-elema-1,3,7(11)-trien-8,12-lactam (5) and 8beta-methoxy-isogermafurenolide (6), one eudesmane-type sesquiterpene, phaeusmane I (7), and one cyclic diarylheptanoid, phaeoheptanoxide (8). Their structures were established based on extensive spectroscopic analysis. The absolute configurations of compounds 1 and 2 were assigned using the circular dichroism data of the [Rh2(OCOCF3)4] complex, and the absolute configuration of 1 was further established by single crystal X-ray crystallography. It is noteworthy that compounds 5-7 were racemates analyzed by chiral HPLC. Furthermore, the inhibitory effects of the isolated compounds on nitric oxide production in LPS activated macrophages were evaluated. Compounds 1, 3 and 4 showed strong inhibitory activities on NO production with IC50 values of 7.46 +/- 0.69, 2.35 +/ 0.17 and 3.49 +/- 0.31 MUM, respectively. A plausible biosynthetic pathway for 1 4 in C. phaeocaulis was also discussed. PMID- 26151446 TI - Effect of C-Type Natriuretic Peptide on Maturation and Developmental Competence of Goat Oocytes Matured In Vitro. AB - The developmental competence of oocytes during in vitro maturation (IVM) is compromised due to asynchronous nuclear and cytoplasmic maturation. To improve IVM efficiency, a pre-maturation culture or two-step maturation strategy has been established, involving meiosis arrest induced by pharmacological agents to provide oocytes with sufficient time to synchronize the maturation of the nucleus and cytoplasm. C-type natriuretic peptide (CNP), which has been demonstrated to function as an oocyte maturation inhibitor (OMI) in many species, provides a new alternative to improve the developmental capacity of oocytes matured in vitro. However, the effect of CNP on meiosis arrest and the maturation of goat oocytes remains unclear. In the present study, CNP was shown to function as an OMI in goat oocytes. CNP could temporarily maintain the meiotic arrest of goat oocytes cultured in vitro for 4 hours. This transient effect was partly due to the reduction of natriuretic peptide receptor 2 (Npr2). Estradiol could delay the decrease in Npr2 expression and prolong the duration of meiosis arrest up to 6 hours. Based on the above results, a two-step method was established for goat oocyte maturation, in which the oocyte maturation rate was significantly increased. After parthenogenetic activation, the cleavage rate, blastocyst rate and total cell number of blastocysts were significantly improved. Our results suggested that CNP can be used to delay meiotic resumption and enhance the developmental competence of goat oocytes matured in vitro. PMID- 26151448 TI - Deletion of Plasmodium falciparum Histidine-Rich Protein 2 (pfhrp2) and Histidine Rich Protein 3 (pfhrp3) Genes in Colombian Parasites. AB - A number of studies have analyzed the performance of malaria rapid diagnostic tests (RDTs) in Colombia with discrepancies in performance being attributed to a combination of factors such as parasite levels, interpretation of RDT results and/or the handling and storage of RDT kits. However, some of the inconsistencies observed with results from Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-based RDTs could also be explained by the deletion of the gene that encodes the protein, pfhrp2, and its structural homolog, pfhrp3, in some parasite isolates. Given that pfhrp2- and pfhrp3-negative P. falciparum isolates have been detected in the neighboring Peruvian and Brazilian Amazon regions, we hypothesized that parasites with deletions of pfhrp2 and pfhrp3 may also be present in Colombia. In this study we tested 100 historical samples collected between 1999 and 2009 from six Departments in Colombia for the presence of pfhrp2, pfhrp3 and their flanking genes. Seven neutral microsatellites were also used to determine the genetic background of these parasites. In total 18 of 100 parasite isolates were found to have deleted pfhrp2, a majority of which (14 of 18) were collected from Amazonas Department, which borders Peru and Brazil. pfhrp3 deletions were found in 52 of the 100 samples collected from all regions of the country. pfhrp2 flanking genes PF3D7_0831900 and PF3D7_0831700 were deleted in 22 of 100 and in 1 of 100 samples, respectively. pfhrp3 flanking genes PF3D7_1372100 and PF3D7_1372400 were missing in 55 of 100 and in 57 of 100 samples. Structure analysis of microsatellite data indicated that Colombian samples tested in this study belonged to four clusters and they segregated mostly based on their geographic region. Most of the pfhrp2-deleted parasites were assigned to a single cluster and originated from Amazonas Department although a few pfhrp2-negative parasites originated from the other three clusters. The presence of a high proportion of pfhrp2-negative isolates in the Colombian Amazon may have implications for the use of PfHRP2-based RDTs in the region and may explain inconsistencies observed when PfHRP2-based tests and assays are performed. PMID- 26151447 TI - Risk of Adverse Pregnancy Outcomes among Women Practicing Poor Sanitation in Rural India: A Population-Based Prospective Cohort Study. AB - BACKGROUND: The importance of maternal sanitation behaviour during pregnancy for birth outcomes remains unclear. Poor sanitation practices can promote infection and induce stress during pregnancy and may contribute to adverse pregnancy outcomes (APOs). We aimed to assess whether poor sanitation practices were associated with increased risk of APOs such as preterm birth and low birth weight in a population-based study in rural India. METHODS AND FINDINGS: A prospective cohort of pregnant women (n = 670) in their first trimester of pregnancy was enrolled and followed until birth. Socio-demographic, clinical, and anthropometric factors, along with access to toilets and sanitation practices, were recorded at enrolment (12th week of gestation). A trained community health volunteer conducted home visits to ensure retention in the study and learn about study outcomes during the course of pregnancy. Unadjusted odds ratios (ORs) and adjusted odds ratios (AORs) and 95% confidence intervals for APOs were estimated by logistic regression models. Of the 667 women who were retained at the end of the study, 58.2% practiced open defecation and 25.7% experienced APOs, including 130 (19.4%) preterm births, 95 (14.2%) births with low birth weight, 11 (1.7%) spontaneous abortions, and six (0.9%) stillbirths. Unadjusted ORs for APOs (OR: 2.53; 95% CI: 1.72-3.71), preterm birth (OR: 2.36; 95% CI: 1.54-3.62), and low birth weight (OR: 2.00; 95% CI: 1.24-3.23) were found to be significantly associated with open defecation practices. After adjustment for potential confounders such as maternal socio-demographic and clinical factors, open defecation was still significantly associated with increased odds of APOs (AOR: 2.38; 95% CI: 1.49-3.80) and preterm birth (AOR: 2.22; 95% CI: 1.29-3.79) but not low birth weight (AOR: 1.61; 95% CI: 0.94-2.73). The association between APOs and open defecation was independent of poverty and caste. Even though we accounted for several key confounding factors in our estimates, the possibility of residual confounding should not be ruled out. We did not identify specific exposure pathways that led to the outcomes. CONCLUSIONS: This study provides the first evidence, to our knowledge, that poor sanitation is associated with a higher risk of APOs. Additional studies are required to elucidate the socio-behavioural and/or biological basis of this association so that appropriate targeted interventions might be designed to support improved birth outcomes in vulnerable populations. While it is intuitive to expect that caste and poverty are associated with poor sanitation practice driving APOs, and we cannot rule out additional confounders, our results demonstrate that the association of poor sanitation practices (open defecation) with these outcomes is independent of poverty. Our results support the need to assess the mechanisms, both biological and behavioural, by which limited access to improved sanitation leads to APOs. PMID- 26151449 TI - Genome Scan for Selection in Structured Layer Chicken Populations Exploiting Linkage Disequilibrium Information. AB - An increasing interest is being placed in the detection of genes, or genomic regions, that have been targeted by selection because identifying signatures of selection can lead to a better understanding of genotype-phenotype relationships. A common strategy for the detection of selection signatures is to compare samples from distinct populations and to search for genomic regions with outstanding genetic differentiation. The aim of this study was to detect selective signatures in layer chicken populations using a recently proposed approach, hapFLK, which exploits linkage disequilibrium information while accounting appropriately for the hierarchical structure of populations. We performed the analysis on 70 individuals from three commercial layer breeds (White Leghorn, White Rock and Rhode Island Red), genotyped for approximately 1 million SNPs. We found a total of 41 and 107 regions with outstanding differentiation or similarity using hapFLK and its single SNP counterpart FLK respectively. Annotation of selection signature regions revealed various genes and QTL corresponding to productions traits, for which layer breeds were selected. A number of the detected genes were associated with growth and carcass traits, including IGF-1R, AGRP and STAT5B. We also annotated an interesting gene associated with the dark brown feather color mutational phenotype in chickens (SOX10). We compared FST, FLK and hapFLK and demonstrated that exploiting linkage disequilibrium information and accounting for hierarchical population structure decreased the false detection rate. PMID- 26151450 TI - Next Generation Semiconductor Based Sequencing of the Donkey (Equus asinus) Genome Provided Comparative Sequence Data against the Horse Genome and a Few Millions of Single Nucleotide Polymorphisms. AB - Few studies investigated the donkey (Equus asinus) at the whole genome level so far. Here, we sequenced the genome of two male donkeys using a next generation semiconductor based sequencing platform (the Ion Proton sequencer) and compared obtained sequence information with the available donkey draft genome (and its Illumina reads from which it was originated) and with the EquCab2.0 assembly of the horse genome. Moreover, the Ion Torrent Personal Genome Analyzer was used to sequence reduced representation libraries (RRL) obtained from a DNA pool including donkeys of different breeds (Grigio Siciliano, Ragusano and Martina Franca). The number of next generation sequencing reads aligned with the EquCab2.0 horse genome was larger than those aligned with the draft donkey genome. This was due to the larger N50 for contigs and scaffolds of the horse genome. Nucleotide divergence between E. caballus and E. asinus was estimated to be ~ 0.52-0.57%. Regions with low nucleotide divergence were identified in several autosomal chromosomes and in the whole chromosome X. These regions might be evolutionally important in equids. Comparing Y-chromosome regions we identified variants that could be useful to track donkey paternal lineages. Moreover, about 4.8 million of single nucleotide polymorphisms (SNPs) in the donkey genome were identified and annotated combining sequencing data from Ion Proton (whole genome sequencing) and Ion Torrent (RRL) runs with Illumina reads. A higher density of SNPs was present in regions homologous to horse chromosome 12, in which several studies reported a high frequency of copy number variants. The SNPs we identified constitute a first resource useful to describe variability at the population genomic level in E. asinus and to establish monitoring systems for the conservation of donkey genetic resources. PMID- 26151451 TI - GntR Family of Bacterial Transcription Factors and Their DNA Binding Motifs: Structure, Positioning and Co-Evolution. AB - The GNTR family of transcription factors (TFs) is a large group of proteins present in diverse bacteria and regulating various biological processes. Here we use the comparative genomics approach to reconstruct regulons and identify binding motifs of regulators from three subfamilies of the GNTR family, FADR, HUTC, and YTRA. Using these data, we attempt to predict DNA-protein contacts by analyzing correlations between binding motifs in DNA and amino acid sequences of TFs. We identify pairs of positions with high correlation between amino acids and nucleotides for FADR, HUTC, and YTRA subfamilies and show that the most predicted DNA-protein interactions are quite similar in all subfamilies and conform well to the experimentally identified contacts formed by FadR from E. coli and AraR from B. subtilis. The most frequent predicted contacts in the analyzed subfamilies are Arg-G, Asn-A, Asp-C. We also analyze the divergon structure and preferred site positions relative to regulated genes in the FADR and HUTC subfamilies. A single site in a divergon usually regulates both operons and is approximately in the middle of the intergenic area. Double sites are either involved in the co operative regulation of both operons and then are in the center of the intergenic area, or each site in the pair independently regulates its own operon and tends to be near it. We also identify additional candidate TF-binding boxes near palindromic binding sites of TFs from the FADR, HUTC, and YTRA subfamilies, which may play role in the binding of additional TF-subunits. PMID- 26151453 TI - Quantum Chemical Studies on Detail Mechanism of Nitrosylation of NAMI-A-HSA Adduct. AB - Hydrolysis of NAMI-A in NAMI-A-HSA (HSA = human serum albumin) and nitrosylation of hydrolyzed NAMI-A-HSA adduct have been studied in detail using density functional theory method. It has been observed that the chloride exchange reaction with water in the NAMI-A-HSA adduct follows an interchange dissociative mechanism passing through an unstable heptacoordinated activated complex. The computed free energy of activation (DeltaG) and rate constant (k) for the hydrolysis process in aqueous medium are observed to be 24.85 kcal mol(-1) and 3.81 * 10(-6) s(-1), respectively. Nitrosylation of hydrolyzed NAMI-A-HSA adduct with nitric oxide is found to be thermodynamically more favorable with the incorporation of solvent effect and provides a detailed understanding related to the antimetastatic activity of the NAMI-A drug. This investigation shows that nitric oxide coordinates linearly to NAMI-A-HSA adduct leading to the reduction of ruthenium(III) to more active ruthenium(II), with the reduction potential of 2.32 V. Negative relative solvation and relative binding free energies suggest that the hydrolysis and nitrosylation reactions are found to be thermodynamically favorable and faster. Our computed results provide a detailed thermodynamics and kinetics which may be highly beneficial for understanding antimetastatic activity as well as the nitric oxide scavenging ability of NAMI-A. PMID- 26151452 TI - Corpus callosum area in patients with bipolar disorder with and without psychotic features: an international multicentre study. AB - BACKGROUND: Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre sample of patients with BD and healthy controls. METHODS: We analyzed anatomic T1 MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features. RESULTS: We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features. LIMITATIONS: We found small to medium effect sizes, and there was no calibration technique among the sites. CONCLUSION: Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD. PMID- 26151454 TI - Synthetic double-stranded RNA induces interleukin-32 in bronchial epithelial cells. AB - OBJECTIVE: Interleukin (IL)-32 is a novel cytokine and is involved in the pathogenesis of various inflammatory diseases, including asthma and COPD. However, the regulatory mechanisms of IL-32 expression and its precise pathogenic role remain to be defined. Given that viral infections are known to potentially cause and exacerbate airway inflammation, in this study, we investigated the expression of IL-32 induced by synthetic double-stranded (ds) RNA, and its signaling mechanisms involved. METHODS: Bronchial epithelial cells were stimulated with synthetic dsRNA poly I:C. The levels of IL-32 expression were analyzed using real-time PCR and ELISA. The involvement of transforming growth factor beta-activated kinase 1 (TAK1) and a subunit of nuclear factor-kappaB (NF kappaB), p65 was determined by western blot analyses. TAK1 inhibitor, 5Z-7 Oxozeaenol and NF-kappaB inhibitor, BAY 11-7082 were added to the culture to identify key signaling events leading to the expression of IL-32. Finally, the effect of short interfering RNAs (siRNAs) targeting TAK1 and p65 was investigated. RESULTS: dsRNA significantly induced IL-32 gene and protein expression, concomitant with activation of TAK1 and p65. Pretreatment of 5Z-7 Oxozeaenol diminished dsRNA-induced phosphorylation of NF-kappaB. Both 5Z-7 Oxozeaenol and BAY 11-7082 significantly abrogated dsRNA-induced IL-32 production. Moreover, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL-32. CONCLUSIONS: The expression of IL-32 is induced by dsRNA via the TAK1-NF-kappaB signaling pathway in bronchial epithelial cells. IL-32 is involved in the pathogenesis of airway inflammation, and may be a novel therapeutic target for airway inflammatory diseases. PMID- 26151455 TI - The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. AB - Aberrant activation of intracellular signalling pathways confers malignant properties on cancer cells. Targeting intracellular signalling pathways has been a productive strategy for drug development, with several drugs acting on signalling pathways already in use and more continually being developed. The JAK/STAT signalling pathway provides an example of this paradigm in haematological malignancies, with the identification of JAK2 mutations in myeloproliferative neoplasms leading to the development of specific clinically effective JAK2 inhibitors, such as ruxolitinib. It is now clear that many solid tumours also show activation of JAK/STAT signalling. In this review, we focus on the role of JAK/STAT signalling in solid tumours, examining the molecular mechanisms that cause inappropriate pathway activation and their cellular consequences. We also discuss the degree to which activated JAK/STAT signalling contributes to oncogenesis. Studies showing the effect of activation of JAK/STAT signalling upon prognosis in several tumour types are summarised. Finally, we discuss the prospects for treating solid tumours using strategies targeting JAK/STAT signalling, including what can be learned from haematological malignancies and the extent to which results in solid tumours might be expected to differ. PMID- 26151458 TI - Use of a Copper Band to Make Resin Cores in Endodontically Treated Teeth Lacking Coronal Structure. AB - This article describes the use of a copper band as a matrix to build up resin cores in endodontically treated teeth that have a partially subgingival margin. The copper band is adjusted to the contour of the remaining dental structure and extends beyond the margins to ensure complete isolation in order to provide a matrix to fabricate a core. PMID- 26151459 TI - Cervical Interfacial Bonding Effectiveness of Class II Bulk Versus Incremental Fill Resin Composite Restorations. AB - Cervical interfacial bonding quality has been a matter of deep concern. The purpose of this study was to analyze microtensile bond strength (MTBS) and cervical interfacial gap distance (IGD) of bulk-fill vs incremental-fill Class II composite restorations. Box-only Class II cavities were prepared in 91 maxillary premolars (n = 7) with gingival margin placement 1 mm above the cementoenamel junction at one side and 1 mm below it on the other side. Eighty-four maxillary premolars were divided into self-etch and total-etch groups and further subdivided into six restorative material subgroups used incrementally and with an open-sandwich technique: group 1, Tetric Ceram HB (TC) as a control; group 2, Tetric EvoFlow (EF); group 3, SDR Smart Dentin Replacement (SDR); group 4, SonicFill (SF); group 5, Tetric N-Ceram Bulk Fill (TN); and group 6, Tetric EvoCeram Bulk Fill (TE). Groups 2-6 were bulk-fill restoratives. Tetric N-Bond Self-Etch (se) and Tetric N-Bond total-etch (te) adhesive were used in subgroups 1-5, whereas AdheSE (se) and ExciTE F (te) were used in subgroup 6. In an additional group, Filtek P90 Low Shrink Restorative (P90) was used only with its corresponding self-etch bond. The materials were manipulated, light-cured (1600 mW/cm(2)), artificially aged (thermal and occlusal load-cycling), and sectioned. Two microrods/restoration (n = 14/group) were tested for MTBS at a crosshead speed of 0.5 mm/min (Instron testing machine). Fracture loads were recorded (Newtons), and MTSBs were calculated (Megapascals). Means were statistically analyzed by the Kruskal-Wallis test, Conover-Inman post hoc analysis for MTBS (multiple comparisons), and Mann-Whitney U test for IGD. The ends of the fractures were examined for failure mode. One microrod/restoration (n = 7/group) was investigated by scanning electron microscopy (*1200) for IGD. MTBS values for SF/te, P90 in enamel, and TC+SDR/te in enamel and cementum were significantly higher compared with those for the control TC/te and TC/se in cementum. Most of the failures were mixed. IGDs were generally smaller at enamel margins, and the smallest IGDs were found in P90 at both enamel and cementum margins. Bulk-fill and silorane-based composites might provide better cervical interfacial quality than incremental-fill restorations. PMID- 26151457 TI - A phase II and pharmacodynamic study of sunitinib in relapsed/refractory oesophageal and gastro-oesophageal cancers. AB - BACKGROUND: Blockade of the vascular endothelial growth factor (VEGF) pathway shows evidence of activity in gastro-oesophageal (GE) and oesophageal cancer. We investigated the efficacy of sunitinib, a multikinase VEGF inhibitor, in patients with relapsed/refractory GE/oesophageal cancer. METHODS: This was a single-stage Fleming phase II study. The primary end point was progression-free survival (PFS) at 24 weeks. If five or more patients out of a total of 25 were free of progressive disease at 24 weeks, sunitinib would be recommended for further study. Patients received sunitinib 37.5 mg orally daily and imaged every 6 weeks. Exploratory correlative analysis included serum growth factors, tumour gene expression and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Twenty-five evaluable patients participated in the study. Progression free survival at 24 weeks was 8% (n=2 patients; confidence interval (CI): 95% 1.4 22.5%), and the duration of best response for the patients was 23 and 72 weeks. Ten patients (42%) had stable disease (SD) for >10 weeks. Overall response rate is 13%. Median PFS is 7 weeks (95% CI: 5.6-11.4 weeks) and the median overall survival is 17 weeks (95% CI: 8.9-25.3 weeks). Most common grade 3/4 toxicities included fatigue (24%), anaemia (20%) thrombocytopenia (16%), and leucopenia (16%). No patients discontinued therapy due to toxicity. Serum VEGF-A and -C levels, tumour complement factor B (CFB) gene expression, and DCE-MRI correlated with clinical benefit, defined as SD or better as best response. CONCLUSION: Sunitinib is well tolerated but only a select subgroup of patients benefited. Serum VEGF-A and -C may be early predictors of benefit. On this study, patients with clinical benefit from sunitinib had higher tumour CFB expression, and thus has identified CFB as a potential predictor for efficacy of anti-angiogenic therapy. These findings need validation from future prospective trials. PMID- 26151460 TI - Can Silanization Increase the Retention of Glass-fiber posts? A Systematic Review and Meta-analysis of In Vitro Studies. AB - The role of silanes in the bonding of resin luting agents to glass-fiber posts (GFPs) is a controversial topic, and the question still remains whether post silanization is able to improve the retention of GFPs luted into root canals. Thus, this study was designed to determine whether evidence exists to justify silanization of GFPs before cementation to increase their retention into root canals. In vitro studies that evaluated the retention of GFPs cemented into root canals or artificial substrates and that used silane coupling agents for pretreatment of the post were selected. Searches were carried out in PubMed and Scopus databases with no publication year or language limits. The last search was carried out in August 2014. Two distinct data analyses were carried out: 1) control group (no post pretreatment) vs silane only and 2) post pretreatment + silane vs silane only. Pooled-effect estimates were obtained by comparing the difference between each bond strength mean value and were expressed as the weighted mean difference between groups (p<=0.05). A total of 178 articles were found, and 23 were included in the review. The results were affected by the substrate into which the GFPs were luted (teeth or artificial devices). The analysis between control group and silane only for studies that used artificial devices favored the use of silane (p<0.0001), but considering studies that used teeth as substrate, no significant difference was observed (p=0.35). The analysis between silane only and pretreatment + silane did not show a significant difference between groups when artificial devices were used (p=0.71), whereas the analysis favored the use of post pretreatment + silane over silane (p<0.00001) only when the GFPs were luted into teeth. In conclusion, this review indicates that silanization improves the retention of GFPs luted into root canals provided that selective surface pretreatments are applied to the post before silanization. PMID- 26151461 TI - Surface Treatments of Zirconia to Enhance Bonding Durability. AB - This article reviewed the surface treatments used most often to improve adhesion between zirconia and adhesive cements, focusing on their capacity to provide long term bonding. Traditional and new treatments for zirconia bonding were searched. Some new treatments were discussed along with topographical views of the modified zirconia. New methods, such as selective infiltration etching and the low-fusing glassy porcelain application are promising, but more research is needed. PMID- 26151462 TI - Effects of Temperature and Aging on Working/Setting Time of Dual-cured Resin Cements. AB - OBJECTIVES: To evaluate the effects of aging and temperature on working time (WT) and setting time (ST) of several dual-cured resin cements. METHODS: WT and ST were determined with a thermo-controlled stage oscillating rheometer. New cement kits were used for the study. Cements were mixed according to instructions and dispensed on the oscillating stage that was preset at 22 degrees C or 37 degrees C. Rheologic charts were generated from the beginning of mixing until no further oscillation was detected. After initial measurements, cement kits were aged at 37 degrees C for 12 weeks, and WT/ST was determined again at both temperatures. Five samples were read for each material and condition. Data were analyzed with repeated measures analysis of variance and a Tukey test at alpha=5% for each individual material. RESULTS: The WT and ST of all cements were significantly affected by temperature and aging (p<0.05). In general, higher temperature accelerated WT/ST, but aging effects were material dependent. Some materials presented reduced WT/ST, whereas others showed increased WT/ST, regardless of the temperature. CONCLUSIONS: The WT and ST were significantly affected by temperature variation and aging condition. Although temperature changes appeared to affect all materials similarly, aging effects were material dependent. PMID- 26151456 TI - Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium. AB - BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow up. A significant OS disadvantage was observed for women who were obese (BMI: 30 34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ?35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer. PMID- 26151463 TI - Mercapto functionalized silica entrapped polyacrylamide hydrogel: Arsenic adsorption behaviour from aqueous solution. AB - In this article, 3-mercaptopropyl functionalized silica entrapped polyacrylamide hydrogel (MPFS-PAA) was prepared and characterized by FT-IR, scanning electron microscopy (SEM) and energy dispersion X-ray spectroscopy (EDS). Synthesized hydrogel was evaluated for removal of arsenic(III) from aqueous solution. Adsorption studies were carried out by batch method as function of contact time, initial concentration of arsenic and pH. As(III) adsorption data fitted well with Langmuir and Freundlich isotherm models. Adsorption capacity of arsenic 92.5 MUg/g was obtained at initial concentration of 100 MUg/L by Langmuir isotherm. Adsorption kinetics was tested for pseudo-second order reaction at different contact time. The rate constants of pseudo second order reaction were calculated and good correlation coefficient R(2) 99.67 obtained. The results indicates that MPFS-PAA is an effective adsorbent for removal of As(III) from aqueous solution. PMID- 26151464 TI - The Mental Health Status of Single-Parent Community College Students in California. AB - Single-parenting students face unique challenges that may adversely affect their mental health, which have not been explored in community college settings. OBJECTIVE: The authors conducted secondary analysis of Spring 2013 data from the American College Health Association-National College Health Assessment to examine difficulties facing single-parent community college students and the association between single parenting and negative mental health (depression, self-injury, suicide attempt). PARTICIPANTS: Participants were 6,832 California community college students, of whom 309 were single parents. METHODS: Demographic and mental health data were characterized using univariate descriptive analyses. Bivariate analyses determined whether single parents differed from other students regarding negative mental health or traumatic/difficult events. RESULTS: Finances, family, and relationship difficulties disproportionally affected single parents, who reported nearly twice as many suicide attempts as their counterparts (5.3% vs. 2.7%; p < .0001). CONCLUSIONS: Single-parenting students face a higher prevalence of mental health stressors than other community college students. PMID- 26151465 TI - A Theory of Unconscious Thought. AB - We present a theory about human thought named the unconscious-thought theory (UTT). The theory is applicable to decision making, impression formation, attitude formation and change, problem solving, and creativity. It distinguishes between two modes of thought: unconscious and conscious. Unconscious thought and conscious thought have different characteristics, and these different characteristics make each mode preferable under different circumstances. For instance, contrary to popular belief, decisions about simple issues can be better tackled by conscious thought, whereas decisions about complex matters can be better approached with unconscious thought. The relations between the theory and decision strategies, and between the theory and intuition, are discussed. We end by discussing caveats and future directions. PMID- 26151466 TI - Embodied Perception and the Economy of Action. AB - Perception informs people about the opportunities for action and their associated costs. To this end, explicit awareness of spatial layout varies not only with relevant optical and ocular-motor variables, but also as a function of the costs associated with performing intended actions. Although explicit awareness is mutable in this respect, visually guided actions directed at the immediate environment are not. When the metabolic costs associated with walking an extent increase-perhaps because one is wearing a heavy backpack-hills appear steeper and distances to targets appear greater. When one is standing on a high balcony, the apparent distance to the ground is correlated with one's fear of falling. Perceiving spatial layout combines the geometry of the world with behavioral goals and the costs associated with achieving these goals. PMID- 26151467 TI - Enlarging the Societal Pie Through Wise Legislation: A Psychological Perspective. AB - We offer a psychological perspective to explain the failure of governments to create near-Pareto improvements. Our tools for analyzing these failures reflect the difficulties people have trading small losses for large gains: the fixed-pie approach to negotiations, the omission bias and status quo bias, parochialism and dysfunctional competition, and the neglect of secondary effects. We examine the role of human judgment in the failure to find wise trade-offs by discussing diverse applications of citizen and government decision making, including AIDS treatment, organ-donation systems, endangered-species protection, subsidies, and free trade. Our overall goal is to offer a psychological approach for understanding suboptimality in government decision making. PMID- 26151468 TI - Reciprocal Effects of Self-Concept and Performance From a Multidimensional Perspective: Beyond Seductive Pleasure and Unidimensional Perspectives. AB - We (Marsh & Craven, 1997) have claimed that academic self-concept and achievement are mutually reinforcing, each leading to gains in the other. Baumeister, Campbell, Krueger, and Vohs (2003) have claimed that self-esteem has no benefits beyond seductive pleasure and may even be detrimental to subsequent performance. Integrating these seemingly contradictory conclusions, we distinguish between (a) older, unidimensional perspectives that focus on global self-esteem and underpin the Baumeister et al. review and (b) more recent, multidimensional perspectives that focus on specific components of self-concept and are the basis of our claim. Supporting the construct validity of a multidimensional perspective, studies show that academic achievement is substantially related to academic self-concept, but nearly unrelated to self-esteem. Consistent with this distinction, research based on our reciprocal-effects model (REM) and a recent meta-analysis show that prior academic self-concept (as opposed to self-esteem) and achievement both have positive effects on subsequent self-concept and achievement. We provide an overview of new support for the generality of the REM for young children, cross cultural research in non-Western countries, health (physical activity), and nonelite (gymnastics) and elite (international swimming championships) sport. We conclude that future reviews elucidating the significant implications of self concept for theory, policy, and practice need to account for current research supporting the REM and a multidimensional perspective of self-concept. PMID- 26151469 TI - Toward a Psychology of Human Agency. AB - This article presents an agentic theory of human development, adaptation, and change. The evolutionary emergence of advanced symbolizing capacity enabled humans to transcend the dictates of their immediate environment and made them unique in their power to shape their life circumstances and the courses their lives take. In this conception, people are contributors to their life circumstances, not just products of them. Social cognitive theory rejects a duality between human agency and social structure. People create social systems, and these systems, in turn, organize and influence people's lives. This article discusses the core properties of human agency, the different forms it takes, its ontological and epistemological status, its development and role in causal structures, its growing primacy in the coevolution process, and its influential exercise at individual and collective levels across diverse spheres of life and cultural systems. PMID- 26151470 TI - MicroRNA-153 suppresses the osteogenic differentiation of human mesenchymal stem cells by targeting bone morphogenetic protein receptor type II. AB - Elucidation of the molecular mechanisms governing the osteogenic differentiation of human mesenchymal stem cells (hMSCs) is of great importance for improving the treatment of bone-related diseases. MicroRNAs (miRNAs or miRs), a class of small non-coding RNAs, are critical in a number of biological processes, including the proliferation, differentiation and survival of cells and organisms. Emerging evidence indicates that miRNAs are essential in regulating osteoblastogenesis and bone formation. However, the role of miRNAs in osteoblast mechanotransduction remains to be defined. The present study aimed to examine the role of miR-153 in the osteogenesis of hMSCs and to investigate the impact of miR-153 on bone morphogenetic protein receptor type II (BMPR2) expression. The overexpression of miR-153 inhibited the osteogenic differentiation of hMSCs, whereas downregulation of miR-153 enhanced the process. Furthermore, bioinformatic analysis predicted that miR-153 is a potential regulator of BMPR2. The direct binding of miR-153 to the BMPR2 3'-untranslated region (3'-UTR) was demonstrated by a luciferase reporter assay using a construct containing the BMPR2 3'-UTR. In addition, knockdown of BMPR2 by RNA interference inhibited the osteogenic differentiation of hMSCs, with a similar effect to the upregulation of miR-153. In conclusion, the results suggest that miR-153 is a mechano-sensitive miRNA that regulates osteoblast differentiation by directly targeting BMPR2, and that therapeutic inhibition of miR-153 may be an efficient anabolic strategy for skeletal disorders caused by pathological mechanical loading. PMID- 26151471 TI - Initial Experience with Percutaneous Angioplasty of the Common Femoral Artery in De Novo Stenotic Lesions. AB - BACKGROUND: The aim of this study was to report an initial experience with percutaneous transluminal angioplasty (PTA) in de novo stenotic lesions of the common femoral artery (CFA). METHODS: A retrospective analysis for 34 consecutive patients was conducted. The follow-up consisted of clinical evaluation and color duplex ultrasound scan (CDU) 1, 6, and 12 months after the procedure. RESULTS: The symptoms were claudication in 16 patients (47%), critical limb ischemia in 17 (50%), and preservation of an infrainguinal bypass in 1 (3%). PTA was performed in CFA alone in 45.7%, associated to iliac and/or profunda/superficial femoral artery PTA in 54.3%. Stenting was performed in 23 patients (65.7%). All procedures were successful. Two patients required surgery for a local complication. Median hospital stay was 2 days. Mean follow-up was 11 months (range 1-56). Primary and secondary sustained clinical improvement rates were 77% and 85%, and primary, CDU-controlled patency rate was 88%. Four reinterventions were required for symptomatic CFA restenosis. At the end of follow-up, no major amputation had been performed, all patients with claudication remained improved with no restenosis, and the secondary sustained improvement rate was 85%. CONCLUSIONS: PTA for primary CFA lesions is feasible and safe, with acceptable short-term results in claudicants. In patients with tissue loss, frequent reinterventions raise questions about PTA benefit. This approach needs to be compared with open surgery in a randomized trial. PMID- 26151472 TI - A 1D anionic lanthanide coordination polymer as an adsorbent material for the selective uptake of cationic dyes from aqueous solutions. AB - A 1D anionic lanthanide coordination polymer {[(CH(3))(2)NH(2)] [(H(2)abtc)(2)Ho(H(2)O)]}n () (H(4)abtc = 3,3',5,5'-azobenzene-tetracarboxylic acid) has been synthesized under hydrothermal reaction conditions. The protonated [(CH(3))(2)NH(2)](+) is generated from decomposed DMA during the reaction, and balances the negative charge of the framework. The as-obtained samples were characterized using single-crystal and powder X-ray diffraction and TGA. Interestingly, 1 can selectively capture cationic dye molecules from mixtures of dye molecules containing different charges in aqueous solutions. Furthermore, 1 exhibits a different adsorption efficiency toward different cationic dyes (crystal violet, rhodamine B, safranine T and methylene blue). Among the studied dyes, methylene blue has a higher adsorption efficiency in comparison to the others. Thus, complex 1 could serve as a good candidate material for the selective removal of cationic dyes during the treatment of wastewater. PMID- 26151473 TI - Editors' Foreword. PMID- 26151474 TI - Ginkgo biloba: A Cognitive Enhancer? AB - Ginkgo biloba is an herb often used as an alternative treatment to improve cognitive functions. Like most herbal treatments, the use of ginkgo is poorly regulated by government agencies, on the basis of either its efficacy or its health risks. This article reviews the experimental evidence available regarding efficacy, neurobiological actions, and health risks. Findings obtained in studies of humans often include demonstrations of rather mild cognitive enhancement. Interpretation of these findings is complicated by somewhat inconsistent findings, by experimental designs that do not permit identification of cognitive functions susceptible to the influence of ginkgo, and by the paucity of direct comparisons with other treatments. The number of peer-reviewed reports of studies in nonhuman animals is surprisingly small. In this small set, the findings reveal mild behavioral effects that might be attributable to actions on cognitive functions. However, these experiments in rodents, like those in humans, do not involve the use of designs to assess ginkgo's effects on particular cognitive attributes, and generally do not include direct comparisons with other treatments. Interpretation of the findings is further complicated by evidence, obtained in studies of both humans and rats, showing that a single administration of the treatment enhances performance on cognitive measures. If ginkgo has effects on cognition, there should be effects evident on biological processes as well. Neurobiological studies have largely examined the effects of chronic ginkgo administration, mirroring the most common design in behavioral studies. However, the addition of findings that single administration of ginkgo may influence behavior directs biological investigations to short-term actions of the treatment. Biological effects of ginkgo include vasodilation, protection of neurons from oxidative stress, and actions mediated by effects via neurotransmitters. Adverse reactions to ginkgo consumption have been observed but are relatively rare. Collectively, the behavioral literature reviewed cannot be used conclusively to document or to refute the efficacy of ginkgo in improving cognitive functions. At best, the effects seem quite modest. In particular, it is questionable whether effects of ginkgo, if present, are equal to those obtained by administration of acetylcholinesterase inhibitors, hearing an arousing story, or ingesting glucose. PMID- 26151475 TI - "Brain-Specific" Nutrients: A Memory Cure? AB - We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phos-phatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antiox idants (particularly vitamin E). In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. In sum, for most of the "brain-specific" nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se. PMID- 26151478 TI - Cesarean section increases the risk of respiratory adaptive disorders in healthy late preterm and two groups of mature newborns. AB - The rates of delivery by Cesarean section (CS) have been trending upwards in recent decades, perhaps leading to higher rates of dysfunction in respiratory adaptation in newborns. We present epidemiological data for pulmonary adaptation by mode of delivery for healthy late preterm and term infants born at a regional tertiary care center. The overall CS rate was 22% with the largest proportion of these in late preterms (39%). This drops to 30% in infants born after 37 weeks gestation and to 11% for those born after 40 weeks. Infants needing respiratory support decreased significantly as gestational age increased: 88% at 34 weeks, 67% at 35 weeks, 28% at 36 weeks, 17% at 37 weeks and 8% at 40 weeks. The risk of respiratory morbidity following CS as compared to vaginal delivery (VD) was substantially higher. 50% of infants born by CS needed respiratory support compared to only 12% following VD. 82% of all late preterm infants born by CS developed respiratory morbidity compared to 36% following VD. Comparable data for infants born after 37 and 40 weeks gestation were 33% compared to 9% and 26% compared to 6% respectively. Late preterm infants born after 36 weeks gestation showed the most marked difference by mode of birth with 66% needing respiratory support following CS as compared to only 9% following VD. Our data could be useful in counselling parents about risk associated with delivery by Cesarean section. A critical view should be taken of increasing CS rates worldwide because of a clear correlation in increased morbidity in infants, especially late preterm infants. PMID- 26151477 TI - SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair. AB - XPC recognizes UV-induced DNA lesions and initiates their removal by nucleotide excision repair (NER). Damage recognition in NER is tightly controlled by ubiquitin and SUMO modifications. Recent studies have shown that the SUMO targeted ubiquitin ligase RNF111 promotes K63-linked ubiquitylation of SUMOylated XPC after DNA damage. However, the exact regulatory function of these modifications in vivo remains elusive. Here we show that RNF111 is required for efficient repair of ultraviolet-induced DNA lesions. RNF111-mediated ubiquitylation promotes the release of XPC from damaged DNA after NER initiation, and is needed for stable incorporation of the NER endonucleases XPG and ERCC1/XPF. Our data suggest that RNF111, together with the CRL4(DDB2) ubiquitin ligase complex, is responsible for sequential XPC ubiquitylation, which regulates the recruitment and release of XPC and is crucial for efficient progression of the NER reaction, thereby providing an extra layer of quality control of NER. PMID- 26151479 TI - Clinical imaging in anti-atherosclerosis drug development. AB - The development of novel drugs for the treatment of atherosclerosis faces many challenges, particularly caused by the need for large and costly outcome trials. When predictive biochemical biomarkers are not available, clinical imaging data can serve as intermediate Phase II endpoints to demonstrate mechanistic and anti atherosclerotic activity of new compounds. These data can support risk mitigation before continuing development in large Phase III outcome trials. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound [intima-media thickness (IMT) and intravascular ultrasound (IVUS)] can provide detailed information on vascular plaque volume and morphology, whereas functional changes can potentially be captured by positron emission tomography (PET) techniques in the vessel wall. We will review the application and operational aspects of clinical imaging methods and endpoints used in interventional atherosclerosis trials. PMID- 26151480 TI - ERK/GSK3beta signaling is involved in atractylenolide I-induced apoptosis and cell cycle arrest in melanoma cells. AB - Novel agents need to be developed to overcome the limitations of the current melanoma therapeutics. Atractylenolide I (AT-I) is a sesquiterpene compound isolated from atractylodis macrocephalae rhizoma. Previous findings demonstrated that AT-I exhibited cytotoxic action in melanoma cells. However, the molecular mechanisms of AT-1's anti-melanoma properties remain to be elucidated. In the present study, the cell cycle-arrest and apoptosis-promoting effects as well as the ERK/GSK3beta signaling-related mechanism of action of AT-I were examined. B16 melanoma cells were treated with various concentrations of AT-1 (50, 75 and 100 uM) for 48 or 72 h. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression levels were detected by western blot analysis. AT-I treatment induced G1 phase arrest, which was accompanied by increased p21 and decreased CDK2 protein expression levels. Apoptosis was observed after AT-I treatment for 72 h, which was accompanied by activated caspase-3 and -8. AT-I treatment significantly decreased phospho-ERK, phospho-GSK3beta, c-Jun and increased p53 protein expression levels. Lithium chloride (LiCl, 5 mM), a GSK3beta inhibitor, treatment alone did not increase the apoptosis of B16 cells, while pretreatment with LiCl markedly reversed AT-I-induced apoptosis. Additionally, AT-I-induced G1 phase arrest was partially reversed by LiCl pretreatment. In conclusion, ERK/GSK3beta signaling was involved in the apoptotic and G1 phase arrest effects of AT-I in melanoma cells. PMID- 26151481 TI - Yellow Pigment Aurovertins Mediate Interactions between the Pathogenic Fungus Pochonia chlamydosporia and Its Nematode Host. AB - Nematophagous fungi are globally distributed soil fungi and well-known natural predators of soil-dwelling nematodes. Pochonia chlamydosporia can be found in diverse nematode-suppressive soils as a parasite of nematode eggs and is one of the most studied potential biological control agents of nematodes. However, little is known about the functions of small molecules in the process of infection of nematodes by this parasitic fungus or about small-molecule-mediated interactions between the pathogenic fungus and its host. Our recent study demonstrated that a P. chlamydosporia strain isolated from root knots of tobacco infected by the root-knot nematode Meloidogyne incognita produced a class of yellow pigment metabolite aurovertins, which induced the death of the free-living nematode Panagrellus redivevus. Here we report that nematicidal P. chlamydosporia strains obtained from the nematode worms tended to yield a total yellow pigment aurovertin production exceeding the inhibitory concentration shown in nematicidal bioassays. Aurovertin D was abundant in the pigment metabolites of P. chlamydosporia strains. Aurovertin D showed strong toxicity toward the root-knot nematode M. incognita and exerted profound and detrimental effects on the viability of Caenorhabditis elegans even at a subinhibitory concentration. Evaluation of the nematode mutation in the beta subunit of F1-ATPase, together with the application of RNA interference in screening each subunit of F1FO-ATPase in the nematode worms, demonstrated that the beta subunit of F1-ATPase might not be the specific target for aurovertins in nematodes. The resistance of C. elegans daf-2(e1370) and the hypersensitivity of C. elegans daf-16(mu86) to aurovertin D indicated that DAF-16/FOXO transcription factor in nematodes was triggered in response to the aurovertin attack. These findings advance our understanding of the roles of aurovertin production in the interactions between nematodes and the pathogen fungus P. chlamydosporia. PMID- 26151482 TI - Optimization of thiamethoxam adsorption parameters using multi-walled carbon nanotubes by means of fractional factorial design. AB - The aim of this work was to evaluate significant factors affecting the thiamethoxam adsorption efficiency using oxidized multi-walled carbon nanotubes (MWCNTs) as adsorbents. Five factors (initial solution concentration of thiamethoxam in water, temperature, solution pH, MWCNTs weight and contact time) were investigated using 2V(5-1) fractional factorial design. The obtained linear model was statistically tested using analysis of variance (ANOVA) and the analysis of residuals was used to investigate the model validity. It was observed that the factors and their second-order interactions affecting the thiamethoxam removal can be divided into three groups: very important, moderately important and insignificant ones. The initial solution concentration was found to be the most influencing parameter on thiamethoxam adsorption from water. Optimization of the factors levels was carried out by minimizing those parameters which are usually critical in real life: the temperature (energy), contact time (money) and weight of MWCNTs (potential health hazard), in order to maximize the adsorbed amount of the pollutant. The results of maximal adsorbed thiamethoxam amount in both real and optimized experiments indicate that among minimized parameters the adsorption time is one that makes the largest difference. The results of this study indicate that fractional factorial design is very useful tool for screening the higher number of parameters and reducing the number of adsorption experiments. PMID- 26151483 TI - Effect of humic substances on phosphorus removal by struvite precipitation. AB - Humic substances (HS) are a major fraction of dissolved organic matters in wastewater. The effect of HS on phosphorus removal by struvite precipitation was investigated using synthetic wastewater under different initial pH values, Mg/P molar ratios and HS concentrations. The composition, morphology and thermal properties of harvested precipitates were analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM) and thermo-gravimetric analysis (TGA), respectively. It showed that inhibition effect of HS reached its maximum value of 48.9% at pH 8.0, and decreased to below 10% at pH>9.0. The increase of Mg/P ratio enhanced phosphorus removal efficiency, and thus reduced the influence of HS on struvite precipitation. At pH 9.0, the inhibitory effect of initial HS concentration matched the modified Monod model with half maximum inhibition concentration of 356mgL(-1), and 29% HS was removed in conjunction with struvite crystallisation. XRD analysis revealed that the crystal form of struvite precipitates was changed in the presence of HS. The morphology of harvested struvite was transformed from prismatic to pyramid owing to the coprecipitation of HS on crystal surface. TGA results revealed that the presence of HS could compromise struvite purity. PMID- 26151484 TI - Hexavalent chromium removal in contaminated water using reticulated chitosan micro/nanoparticles from seafood processing wastes. AB - Chitosan particles (CH) were obtained from seafood processing wastes (shrimp shells) and physicochemically characterized; deacetylation degree of CH was measured by Infrared Spectroscopy (FTIR) and potentiometric titration; polymer molecular weight was determined by intrinsic viscosity measurements. Reticulated micro/nanoparticles of chitosan (MCH) with an average diameter close to 100nm were synthesized by ionic gelation of chitosan using tripolyphosphate (TPP), and characterized by SEM, size distribution and Zeta-potential. Detoxification capacities of CH and MCH were tested analyzing the removal of hexavalent chromium Cr(VI) from contaminated water, at different initial chromium concentrations. The effect of pH on adsorption capacity of CH and MCH was experimentally determined and analyzed considering the Cr(VI) stable complexes (anions) formed, the presence of protonated groups in chitosan particles and the addition of the reticulating agent (TPP). Chitosan crosslinking was necessary to adsorb Cr(VI) at pH<2 due to the instability of CH particles in acid media. Langmuir isotherm described better than Freundlich and Temkin equations the equilibrium adsorption data. Pseudo-second order rate provided the best fitting to the kinetic data in comparison to pseudo-first order and Elovich equations. Chemical analysis to determine the oxidation state of the adsorbed Cr, showed that Cr(VI) was adsorbed on CH particles without further reduction; in contrast Cr(VI) removed from the solution was reduced and bound to the MCH as Cr(III). The reduction of toxic Cr(VI) to the less or nontoxic Cr(III) by the reticulated chitosan micro/nanoparticles can be considered a very efficient detoxification technique for the treatment of Cr(VI) contaminated water. PMID- 26151485 TI - Charge Detection Mass Spectrometry Identifies Preferred Non-Icosahedral Polymorphs in the Self-Assembly of Woodchuck Hepatitis Virus Capsids. AB - Woodchuck hepatitis virus (WHV) is prone to aberrant assembly in vitro and can form a broad distribution of oversized particles. Characterizing aberrant assembly products is challenging because they are both large and heterogeneous. In this work, charge detection mass spectrometry (CDMS) is used to measure the distribution of WHV assembly products. CDMS is a single-particle technique where the masses of individual ions are determined from simultaneous measurement of each ion's charge and m/z (mass-to-charge) ratio. Under relatively aggressive, assembly promoting conditions, roughly half of the WHV assembly products are T=4 capsids composed of exactly 120 dimers while the other half are a broad distribution of larger species that extends to beyond 210 dimers. There are prominent peaks at around 132 dimers and at 150 dimers. In part, the 150 dimer complex can be attributed to elongating a T=4 capsid along its 5-fold axis by adding a ring of hexamers. However, most of the other features cannot be explained by existing models for hexameric defects. Cryo-electron microscopy provides evidence of elongated capsids. However, image analysis reveals that many of them are not closed but have "spiral-like" morphologies. The CDMS data indicate that oversized capsids have a preference for growth by addition of 3 or 4 dimers, probably by completion of hexameric vertices. PMID- 26151486 TI - Histone deacetylases: Targets for antifungal drug development. AB - The interaction of pathogens and its hosts causes a drastic change in the transcriptional landscape in both cells. Among the several mechanisms of gene regulation, transcriptional initiation is probably the main point. In such scenario, the access of transcriptional machinery to promoter is highly regulated by post-translational modification of histones, such as acetylation, phosphorylation and others. Inhibition of histone deacetylases is able to reduce fungal pathogens fitness during infection and, therefore, is currently being considered for the development of new antifungal therapy strategies. PMID- 26151487 TI - Phytochemical Investigation of the Constituents Derived from the Australian Plant Macropidia fuliginosa. AB - A phytochemical study of the flowers and bulbs derived from the Australian plant Macropidia fuliginosa, involving hyphenated spectroscopic methodologies (HPLC-NMR and HPLC-MS), together with conventional isolation strategies, resulted in the identification of 16 constituents (1, 2, 4-17) representative of six different structural classes. Six new compounds (12-17) were identified from the bulbs of the plant. The isolated compounds were assessed for antimicrobial activity, and compound 8 was found to be more potent against P. aeruginosa than ampicillin. PMID- 26151488 TI - Emerging opportunities for the treatment of metabolic diseases: Glucagon-like peptide-1 based multi-agonists. AB - Obesity is a pathogenic gateway to the metabolic syndrome and the complications thereof, thus interventions aimed at preventing or reversing the metabolic derangements underlying obesity hold great therapeutic promise. However, the complexity of energy balance regulation, combined with the heterologous pathophysiology of human obesity, renders effective medicinal intervention very difficult. Indeed, the search for the silver bullet in anti-obesity medicines has been laden with drugs of underwhelming efficacy and unacceptable side effects. This can partly be the consequence that many of these drug interventions have been historically directed at single molecular targets. New multi-molecular combination therapies have shown promising clinical outcomes in terms of weight loss, yet multi-functional single molecules may offer even more advantages than adjunctive co-treatments. Single molecules with integrated activities derived from multiple hormones involved in the physiological control of metabolism have emerged as one of the more promising candidates for reversing obesity. The inclusion of glucagon-like peptide-1 (GLP-1) as one of the constituents is a unifying factor amongst the majority of these unimolecular multi-agonists. The scope of this review is to summarize the current preclinical and clinical landscape of GLP-1-based therapies, focusing on combinatorial therapies with a particular emphasis on single molecule compounds displaying multi-agonist properties. PMID- 26151489 TI - Preparation and synthetic value of pi-bond-rich branched hydrocarbons. AB - The two simplest branched acyclic structures comprising only conjugated C?C units, namely, [3]dendralene (3-methylene-1,4-pentadiene) and [4]dendralene (3,4 dimethylene-1,5-hexadiene), were first reported in 1955 and 1962, respectively. No higher members of the series were described in the literature until 2000. This Account describes the modern phase of dendralene chemistry, driven to a large extent by research performed within the author's group. The first synthesis of the parent dendralene family allowed access to the hydrocarbons in batches of up to 5 mg. The synthetic approach took into account the prevailing dogma of the time, specifically that these compounds would be very reactive species and hence difficult to handle in the laboratory. As such, a route involving the cheleotropic elimination of SO2 from stable, and generally insoluble, 3-sulfolene masked precursors was devised. Our second-generation approach was of significantly higher value in preparative terms, allowing the syntheses of the first six members of the unsubstituted [n]dendralenes (i.e., n = 3-8) directly, on scales of hundreds of milligrams to decagrams, using commercially available precursors and standard laboratory equipment and methods. This work demonstrated that the assumed high reactivity and instability this family of compounds was erroneous and ultimately led to the development of syntheses of structurally related cross-conjugated systems including substituted dendralenes, tetravinylethylene, 1,1-divinylallene, and furan-containing analogues of the dendralenes. Cross-coupling reactions feature strongly in the syntheses of these compounds, and methods involving single- to multifold Stille, Kumada, and Negishi couplings are mainstays of this work. The even parity [n]dendralenes were shown to exhibit enhanced stability over the odd parity congeners, a result that can be attributed to conformational effects. pi-Bond-rich branched hydrocarbons are demonstrated to have significant value in the rapid generation of structural complexity. Pericyclic processes are particularly useful in this regard, with the dendralenes and their relatives serving as multidienes, participating in diene transmissive cycloaddition sequences, sometimes in combination with electrocyclizations, to generate fused and bridged multicyclic systems containing many new covalent bonds. The outcomes of exploratory investigations into pericyclic sequences involving dendralenes are presented, along with methods developed to control chemoselectivity, regioselectivity, and stereoselectivity. Distinct from their use in diene-transmissive sequences, the dendralenes also serve as multialkenes, for the direct synthesis of polyols and oligo cyclopropanes. Finally, the deployment of pi-bond-rich branched hydrocarbons in the shortest total synthesis of a pseudopterosin natural product is summarized, as a prelude to future prospects in the areas of hydrocarbon chemistry and target synthesis. PMID- 26151490 TI - Predicting pubertal development by infantile and childhood height, BMI, and adiposity rebound. AB - BACKGROUND: Despite substantial heritability in pubertal development, children differ in maturational tempo. HYPOTHESES: (i) puberty and its duration are influenced by early changes in height and adiposity. (ii) Adiposity rebound (AR) is a marker for pubertal tempo. METHODS: We utilized published prospective data from 659 girls and 706 boys of the Study of Early Child Care and Youth Development. We investigated the age of pubarche-thelarche-gonadarche-menarche as a function of early height, BMI, and AR. RESULTS: In girls, height standard deviation scores correlated negatively with thelarche and pubarche from 15 mo of age and with menarche from 54 mo. BMI correlated negatively with thelarche from 36 mo of age and menarche from 54 mo. In boys, age at gonadarche correlated negatively with height from 36 mo of age. An AR was detected in 47% of girls and 55% of boys, who became heavier and had earlier and faster puberty than those with no AR. CONCLUSION: The onset and tempo of puberty are influenced by a two hit program. The first is exerted during the infancy-childhood transition (ICT; 6 12 mo) and includes height, as an early predictor of maturational tempo. The second hit occurs at the childhood-juvenility transition (5-7 y) and is based on adiposity and its rebound. PMID- 26151491 TI - Mechanisms of cough provocation and cough resolution in neonates with bronchopulmonary dysplasia. AB - BACKGROUND: Cough and deglutition are protective mechanisms that defend against aspiration. We identified mechanisms associated with cough provocation as well as those associated with cough resolution in infants with bronchopulmonary dysplasia (BPD). METHODS: Manometry signatures of cough were recognized in 16 premature infants with BPD undergoing concurrent esophageal manometry, respiratory inductance plethysmography, and nasal air flow measurements. Pretussive and post tussive pharyngo-esophageal motility changes were analyzed. Mechanisms associated with cough and mechanisms that restored respiratory and esophageal normalcy were analyzed. RESULTS: We analyzed 312 cough events during 88 cough clusters; 97% were associated with recognizable manometric patterns. Initial mechanisms related with coughing included nonpropagating swallow (59%), upper esophageal sphincter (UES) reflex contraction (18%), and lower esophageal sphincter (LES) relaxation (14%). UES and LES dysfunction was present in 69% of nonpropagating swallow associated cough clusters. Mechanisms restoring post-tussive normalcy included primary peristalsis (84%), secondary peristalsis (8%), and none recognized (8%). UES contraction reflex was associated with cough clusters more frequently in infants on nasal continuous positive airway pressure (NCPAP) (OR = 9.13, 95% CI = 1.88-44.24). CONCLUSION: Cough clusters in infants with BPD had identifiable etiologies associated with esophageal events; common initial mechanisms were of upper aerodigestive origin, while common clearing mechanisms were peristaltic reflexes. PMID- 26151493 TI - Probiotic Lactobacillus rhamnosus GG therapy and microbiological programming in infantile colic: a randomized, controlled trial. AB - BACKGROUND: Probiotic Lactobacillus reuteri and reduced allergen load may lessen the daily crying of colic infants, but the role of Lactobacillus rhamnosus GG (LGG) has remained obscure. METHODS: Infants with colic (n = 30) were enrolled during the first 6 wk of life. All families received behavioral support and allergen avoidance diet: breastfeeding mothers followed cow's milk elimination diet and formula-fed infants received extensively hydrolyzed casein formula. The randomized, double-blind intervention employed of LGG 4.5 * 10(9) cfu/d or placebo for a 4-wk study period. Daily crying was recorded by diaries and parental interviews. Fecal calprotectin and gut microbiota composition by quantitative PCR were evaluated before and after the intervention. RESULTS: Daily crying time was comparable between the probiotic (173 min) and the placebo group (174 min; P = 0.99) at the end of the intervention according to the parental diary. However, parents reported a decrease of 68% (95% confidence interval (CI): 58-78) in daily crying in the probiotic and 49% (95% CI: 32-66) in the placebo group (P = 0.05). CONCLUSION: LGG in infants treated in tandem with behavioral support and a cow's milk elimination diet did not provide additional treatment effect for diary-verified colic crying although parental report of crying suggested the probiotic intervention effective. PMID- 26151492 TI - Decreased renal function in overweight and obese prepubertal children. AB - BACKGROUND: Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl). METHODS: Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference. RESULTS: Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to 1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values. CONCLUSION: Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity. PMID- 26151494 TI - Salivary and serum cortisol and relation to blood pressure in infancy and early childhood in very-low-birth-weight infants. AB - BACKGROUND: Programming of the hypothalamic-pituitary-adrenal (HPA) axis possibly explains the relation between intrauterine growth restriction (IUGR) and/or preterm birth and elevated blood pressure in later life. Very-low-birth-weight infants (birth weight <1,500 g) have high prevalence of raised blood pressure, already in early childhood. We investigated cortisol levels, relation to blood pressure and reliability of salivary cortisol in infancy and early childhood in very-low-birth-weight infants. METHODS: We included 41 children, participating in the randomized controlled Neonatal Insulin Replacement Therapy in Europe (NIRTURE) trial. Serum and salivary samples for cortisol measurement (immunoassay) were taken simultaneously at 6 mo and separately at 2 y corrected age. Blood pressure was measured at 2 y corrected age. RESULTS: Serum cortisol was significantly correlated to systolic and diastolic blood pressure in boys and in the early-insulin treated group. At 2 y corrected age serum cortisol was significantly higher in the early-insulin group compared to the standard care group. At 6 mo corrected age salivary cortisol was significantly correlated to serum cortisol. CONCLUSION: In very-low-birth-weight boys, the positive correlation between cortisol and blood pressure is present at 2 y corrected age. Early insulin therapy could affect programming of the HPA axis. Salivary cortisol mirrors serum levels at 6 mo corrected age. PMID- 26151495 TI - Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and catenin pathway after spinal cord injury. AB - Aberrant functionality of the cell cycle has been implicated in the pathology of traumatic SCI. Although it has been reported that the expressions of various cell cycle related proteins were altered significantly following SCI, detailed information on the subject remains largely unclear. The embryonic pyruvate kinase M2 (PKM2) is an important metabolic kinase in aerobic glycolysis or the warburg effect, however, its functions in central nervous system (CNS) injury remains elusive. Here we demonstrate that PKM2 was not only significantly upregulated by western blot and immunohistochemistry but certain traumatic stimuli also induced translocation of PKM2 into the nucleus in astrocytes following spinal cord injury (SCI). Furthermore, the expression levels and localization of p-beta-catenin, p27, cyclin D1 and PCNA were correlated with PKM2 after SCI. In vitro, we also found that PKM2 co-immunoprecipitation with p-beta-catenin and p27 respectively. Knockdown of PKM2 apparently decreased the level of PCNA, cyclinD1, p27 in primary astrocyte cells. Taken together, our findings indicate that nuclear translocation of PKM2 promotes astrocytes proliferation after SCI through modulating cell cycle signaling. These discoveries firstly uncovered the role of PKM2 in spinal cord injury and provided a potential therapeutic target for CNS injury and repair. PMID- 26151496 TI - Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. AB - Graves' disease is the leading cause of hyperthyroidism affecting 1.0-1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves' disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 * 10(-32)) and HLA-DRB1*08:03 (Pcombined=1.83 * 10(-9)) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13-41.48) and 6.13 (95% confidence interval=3.28-11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 * 10(-21), 95% confidence interval=21.66-108.22). Our results could be useful for antithyroid induced agranulocytosis and potentially for agranulocytosis caused by other chemicals. PMID- 26151499 TI - Correction to Recognition of Dual Targets by a Molecular Beacon-Based Sensor: Subtyping of Influenza A Virus. PMID- 26151498 TI - Demographic factors predict magnitude of conditioned fear. AB - There is substantial variability across individuals in the magnitudes of their skin conductance (SC) responses during the acquisition and extinction of conditioned fear. To manage this variability, subjects may be matched for demographic variables, such as age, gender and education. However, limited data exist addressing how much variability in conditioned SC responses is actually explained by these variables. The present study assessed the influence of age, gender and education on the SC responses of 222 subjects who underwent the same differential conditioning paradigm. The demographic variables were found to predict a small but significant amount of variability in conditioned responding during fear acquisition, but not fear extinction learning or extinction recall. A larger differential change in SC during acquisition was associated with more education. Older participants and women showed smaller differential SC during acquisition. Our findings support the need to consider age, gender and education when studying fear acquisition but not necessarily when examining fear extinction learning and recall. Variability in demographic factors across studies may partially explain the difficulty in reproducing some SC findings. PMID- 26151497 TI - Low voltage alpha EEG phenotype is associated with reduced amplitudes of alpha event-related oscillations, increased cortical phase synchrony, and a low level of response to alcohol. AB - Low voltage EEG (LVEEG) is a heritable phenotype that differs depending on ancestral heritage, yet its impact on brain networks and cognition remain relatively unexplored. In this study we assessed energy and task related phase locking of event-related oscillation (EROs), behavioral responses, measures of IQ and personality, and expected responses to alcohol in a large sample of individuals with LVEEG compared to those with higher voltage variants. Participants (n=762) were recruited from a Native American community and completed a diagnostic interview, the Quick Test, the Subjective High Assessment Scale Expectation Version (SHAS-E) and the Maudsley Personality Inventory. Clinical and spectral analyzed EEGs were collected for determination of the presence of a LVEEG variant. EROs were generated using a facial expression recognition task. Participants with LVEEG (n=451) were significantly more likely to be older, married and have higher degrees of Native American heritage but did not differ in gender, income or education. Individuals with LVEEG were also found to have decreased energy in their alpha EROs, increased phase locking between stimulus trials, and increased phase-locking between cortical brain areas. No significant differences in the cognitive tests, personality variables or alcohol dependence or anxiety diagnoses were found, however, individuals with LVEEG did report a larger number of drinks ever consumed in a 24-h period and a less intense expected response to alcohol. These data suggest that alpha power in the resting EEG is highly associated with energy and cortical connectivity measures generated by event-related stimuli, as well as potentially increased risk for alcohol use. PMID- 26151500 TI - American Indians' response to physical pain: functional limitations and help seeking behaviors. AB - Seventy-five American Indians, ages 25 to 84, representing 14 tribal nations, participated in this study. The historical, cultural, and behavioral responses to physical pain were examined. Data were collected over a 7-month period with a survey instrument that included the Universal Pain Scale, activities of daily living, causes of pain, cultural beliefs, and self-help-seeking behaviors. Also, recommendations for Western biomedical health care professionals are offered to improve services for the American Indian population. Findings demonstrate that culture plays a crucial role in wellness and significantly affects help-seeking behaviors, treatment regimens, responses to pain, and pain management. PMID- 26151501 TI - Phonon dispersion of silicene on ZrB2(0 0 0 1). AB - We measured the phonon dispersion of silicene (monolayer Si with a honeycomb lattice) on ZrB2(0 0 0 1) using high-resolution electron energy loss spectroscopy. The measured phonon dispersion was compared with ab initio density functional theory calculations for a silicene model with [Formula: see text] periodicity of the substrate. The most stable [Formula: see text] silicene structure, which is similar to the so-called 'planar-like' model (Lee C C et al 2013 Phys. Rev. B 88 165404) reproduced the observed phonon modes very well. The recently reported soft phonon around the [Formula: see text] point (Lee C C et al 2014 Phys. Rev. B 90 241402(R)) was not reproduced, either experimentally or theoretically. The calculated electronic structure revealed that the silicene was metallic on ZrB2(0 0 0 1) and semiconducting on ZrC(1 1 1). PMID- 26151502 TI - Polydopamine-Coated Magnetic Composite Particles with an Enhanced Photothermal Effect. AB - Recently, photothermal therapy (PTT) that utilizes photothermal conversion (PTC) agents to ablate cancer under near-infrared (NIR) irradiation has attracted a growing amount of attention because of its excellent therapeutic efficacy and improved target selectivity. Therefore, exploring novel PTC agents with an outstanding photothermal effect is a current research focus. Herein, we reported a polydopamine-coated magnetic composite particle with an enhanced PTC effect, which was synthesized simply through coating polydopamine (PDA) on the surface of magnetic Fe3O4 particles. Compared with magnetic Fe3O4 particles and PDA nanospheres, the core-shell nanomaterials exhibited an increased NIR absorption, and thus, an enhanced photothermal effect was obtained. We demonstrated the in vitro and in vivo effects of the photothermal therapy using our composite particles and their ability as a contrast agent in the T2-weighted magnetic resonance imaging. These results indicated that the multifunctional composite particles with enhanced photothermal effect are superior to magnetic Fe3O4 particles and PDA nanospheres alone. PMID- 26151504 TI - Palladium-Catalyzed Chelation-Assisted Regioselective Oxidative Dehydrogenative Homocoupling/Ortho-Hydroxylation in N-Phenylpyrazoles. AB - A palladium-catalyzed pyrazole-directed regioselective oxidative C(sp2)-H functionalization of the N-phenyl ring in N-phenylpyrazoles to afford either a biaryl bis-pyrazole (via dehydrogenative homocoupling) or N-(o hydroxyphenyl)pyrazole (via C-H oxygenation) or their mixture is described. The substitutions on the N-phenyl ring and the pyrazole ring and the dilution of the reaction medium with respect to the TFA/TFAA mixture (substrate concentration) have a remarkable influence on the outcome of the reaction. It was discovered that if the reactions were performed under highly dilute conditions (ca. 10 times) then N-(o-hydroxyphenyl)pyrazoles were the major or the sole products. PMID- 26151503 TI - Hepatitis C virus NS3 protein modulates the biological behaviors of malignant hepatocytes by altering the expression of host cell microRNA. AB - Chronic hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. The HCV non-structural protein 3 (NS3) protein is considered to affect normal cellular functions and to be involved in HCV carcinogenesis. The expression of microRNA (miRNA) is altered in human HCC, thus implicating its role in hepatocarcinogenesis. To investigate the mechanisms by which the HCV NS3 protein affects the expression of miRNA in malignant hepatocytes, if any, the present study constructed expression vectors encoding the HCV NS3 and NS3/4A proteins, which were stably transfected into HepG2 cells. The biological behaviors of the HepG2 transfectants and their differential expression levels of miRNA expression were investigated. Compared with the HepG2 vector cells, the HepG2-NS3 cells grew at a slower rate, were arrested in the G0/G1 cell cycle phase, formed more colonies and developed larger tumors at a faster rate. Co-expression of HCV NS4A resulted in the inhibition of HCV NS3 stimulated tumorigenicity. A total of 35 miRNAs were dysregulated, 26 of which were downregulated and nine of which were upregulated, in the HepG2-NS3 cells, and 75 miRNAs were altered in HepG2-NS3/4A cells, of which 20 were downregulated and 55 were upregulated). In addition, significant decreases in the mRNA levels of p53 and p21 were observed, which confirmed differential expression of miRNA. These results suggested that differential miRNA profiling in malignant hepatocytes may account for the variable pathophysiological manifestations associated with the HCV NS3 protein. These differentially expressed miRNAs may offer potential as candidates for the development of miRNA-based therapeutics. PMID- 26151505 TI - Lethal now or lethal later: The natural history of Grade 4 blunt cerebrovascular injury. AB - BACKGROUND: Grade 4 blunt cerebrovascular injury (BCVI4) has a known, significant rate of stroke. However, little is known about the natural history of BCVI4 and the pathophysiology of subsequent stroke formation. METHODS: A 4-year review of patients with BCVI4 at the R Adams Cowley Shock Trauma Center was performed. Rates of BCVI4-related stroke, stroke-related mortality, and overall mortality were calculated. The relationship of change in vessel characteristics and BCVI4 related stroke was examined, as was the mechanism of stroke formation. RESULTS: There were 82 BCVI4s identified, with 13 carotid artery (ICA) and 69 vertebral artery BCVI4s. BCVI4-related stroke rate was 2.9% in vertebral artery BCVI4 and 70% in ICA BCVI4 patients surviving to reimaging. Stroke mechanisms included embolic strokes, thrombotic strokes, and combined embolic and thrombotic strokes. Peristroke vessel recanalization and an embolic stroke mechanism were seen in 100% of ICA BCVI4-related strokes developing after admission. BCVI4-related stroke occurred within 10 hours of hospital admission in 67% of the patients with strokes. Contraindications to anticoagulation were present in most patients with BCVI4-related stroke developing after admission. CONCLUSION: Multiple etiologies of stroke formation exist in BCVI4. Early risk-benefit analysis for initiation of anticoagulation or antiplatelet agents should be performed in all patients with BCVI4, and the use of endovascular vessel occlusion should be considered in those with true contraindications to anticoagulation. However, more aggressive medical therapy may be needed to lessen BCVI4-related stroke development. LEVEL OF EVIDENCE: Prognostic study, level IV; therapeutic study, level V. PMID- 26151506 TI - Minimally invasive is maximally effective: Diagnostic and therapeutic laparoscopy for penetrating abdominal injuries. AB - BACKGROUND: Laparoscopic techniques have evolved, allowing increased capabilities within most subspecialties of general surgery, but have failed to gain traction managing injured patients. We hypothesized that laparoscopy is effective in the diagnosis and treatment of penetrating abdominal injuries. METHODS: We retrospectively reviewed patients undergoing abdominal exploration following penetrating trauma at our Level 1 trauma center during a 6-year period from January 1, 2008, to December 31, 2013. Demographic and resuscitation data were obtained from our trauma registry. Charts were reviewed for operative details, hospital course, and complications. Hospital length of stay (LOS) and complications were primary end points. Patients were classified as having nontherapeutic diagnostic laparoscopy (DL), nontherapeutic diagnostic celiotomy (DC), therapeutic laparoscopy (TL), or therapeutic celiotomy (TC). TL patients were case-matched 2:1 with TC patients having similar intra-abdominal injuries. RESULTS: A total of 518 patients, including 281 patients (55%) with stab wounds and 237 patients (45%) with gunshot wounds, were identified. Celiotomy was performed in 380 patients (73%), laparoscopy in 138 (27%), with 44 (32%) converted to celiotomy. Nontherapeutic explorations were compared including 70 DLs and 46 DCs with similar injury severity. LOS was shorter in DLs compared with DCs (1 day vs. 4 days, p < 0.001). There were no missed injuries. Therapeutic explorations were compared by matching all TL patients 2:1 to TC patients with similar type and severity of injuries. Twenty-four patients underwent TL compared with 48 TC patients in the case matched group. LOS was shorter in the TL group than in the TC group (4 days vs. 2 days, p < 0.001). Wound infections were more common with open exploration (10.4% vs. 0%, p = 0.002), and more patients developed ileus or small bowel obstruction after open exploration (9.4% vs. 1.1%, p = 0.018). CONCLUSION: Laparoscopy is safe and accurate in penetrating abdominal injuries. The use of laparoscopy resulted in shorter hospitalization, fewer postoperative wound infection and ileus complications, as well as no missed injuries. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 26151507 TI - The validity of abdominal examination in blunt trauma patients with distracting injuries. AB - BACKGROUND: Many trauma care providers often disregard the abdominal clinical examination in the presence of extra-abdominal distracting injuries and mandate abdominal computed tomographic scan in these patients. Ignoring the clinical examination may incur undue expense and radiation exposure. The purpose of this study was to assess the efficacy of abdominal clinical examination in patients with distracting injuries. METHODS: During a 1-year period, all awake and alert blunt trauma patients with Glasgow Coma Scale (GCS) score of 14 or 15 were entered into a prospective study. Abdominal clinical examination was performed and documented prospectively on all patients. Abdominal clinical examination included four-quadrant anterior abdominal palpation, flank palpation, lower thoracic palpation, pelvis examination, and palpation of the thoracolumbar spine. Following examination documentation, all patients underwent computed tomographic scan of the abdomen and pelvis with intravenous contrast. RESULTS: A total of 803 patients were enrolled: 451 patients had distracting injuries, and 352 patients did not. Of the 352 patients without distracting injuries, 19 (5.4%) had intra abdominal injuries, of whom 2 (10.5%) had negative clinical examination result. Of the 451 patients with distracting injuries, 48 (10.6%) were diagnosed with intra-abdominal injury, of whom 5 (10.4%) had negative clinical examination result. All five missed injuries in patients with distracting injuries were solid organ injuries, none of which required surgical intervention or blood transfusion. The sensitivity and negative predictive value of abdominal examination for patients with distracting injuries were 90.0% and 97.0%, respectively. The sensitivity and negative predictive value of abdominal examination for surgically significant and transfusion-requiring injuries were both 100%. CONCLUSION: Distracting injuries do not seem to diminish the efficacy of clinical abdominal examination for the diagnosis of clinically significant abdominal injury. These data suggest that clinical examination of the abdomen is valid in awake and alert blunt trauma patients, regardless of the presence of other injuries. LEVEL OF EVIDENCE: Diagnostic study, level III. PMID- 26151508 TI - A reassessment of the impact of trauma systems consultation on regional trauma system development. AB - BACKGROUND: Previous studies have shown that trauma systems decrease morbidity and mortality after injury, but progress in system development has been slow and inconsistent. This study evaluated the progress in 20 state or regional systems following a consultative visit conducted by the Trauma Systems Evaluation and Planning Committee (TSEPC) of the Committee on Trauma, expanding on a previous study published in 2008, which demonstrated significant progress in six systems following consultation. METHODS: Twenty trauma systems that underwent TSEPC consultation between 2004 and 2010 were studied. Status was assessed using a set of 16 objective indicators. Baseline scores for 14 regions were calculated during the consultation visit and taken from the 2008 study for the remaining six. Postconsultation status was assessed during facilitated teleconferences. Progress was assessed by comparing changes in indicator scores. RESULTS: There was significant improvement in approximately 80% of systems evaluated within 60 months following the consultation. There was no progress in five of six systems reevaluated over 80 months after consultation, and all four systems evaluated over 100 months after consultation showed erosion of progress. Significant improvements were seen in 10 of the 16 individual indicators, with the greatest gains related to system standards, data systems, performance improvement, prehospital triage criteria, and linkages with public health. Consistent with the 2008 study, the two indicators related to financing for the trauma system showed no improvement. CONCLUSION: The TSEPC consultation process continues to be associated with improvements in trauma system development in approximately 80% of cases, consistent with the 2008 study, but gains are not self-sustaining. There was a stagnation in progress and a deterioration in total score over time, suggesting that a repeat consultation may be beneficial. System funding remains a challenge and was the area most likely to suffer setbacks over during study period. LEVEL OF EVIDENCE: Care management study, level V. PMID- 26151509 TI - Pediatric trauma and the Pediatric Trauma Society: Our time has come. PMID- 26151510 TI - Implementation of pediatric cervical spine clearance guidelines at a combined trauma center: Twelve-month impact. AB - BACKGROUND: Pediatric cervical spine clearance guidelines should reduce computed tomography (CT) usage in combined pediatric and adult trauma centers biased by adult CT clearance. METHODS: Cervical spine clearance under age 15 years was compared 12 months before (128 patients) and after (105 patients) guideline implementation, emphasizing National Emergency X-Radiography Utilization Study (NEXUS) criteria when appropriate. RESULTS: CT scans in patients clearable by NEXUS criteria decreased 23% (p = 0.01) and decreased by 16% in cases where radiography other than CT was indicated by guidelines (p = 0.01). CONCLUSION: Guideline implementation can have an immediate effect in decreasing pediatric cervical spine CT usage and should improve across time. LEVEL OF EVIDENCE: Care management study, level IV. PMID- 26151511 TI - Utility of magnetic resonance imaging in diagnosing cervical spine injury in children with severe traumatic brain injury. AB - BACKGROUND: Evaluation of children for cervical spine injuries (CSIs) after blunt trauma is complicated, particularly if the patient is unresponsive because of severe traumatic brain injury. Plain radiography and computed tomography (CT) are commonly used, but CT combined with magnetic resonance imaging (MRI) is still considered the gold standard in CSI detection. However, MRI is expensive and can delay cervical clearance. The purpose of this study is to determine the added benefit of MRI as an adjunct to CT in the clearance of children with severe head trauma. METHODS: We performed a retrospective chart review of pediatric head trauma patients admitted to the pediatric intensive care unit at St. Louis Children's Hospital from 2002 to 2012. Patients who received both cervical spine CT and MRI and presented with a Glasgow Coma Scale score of 8 or lower were included in the study. Imaging was analyzed by two pediatric trauma subspecialists and classified as demonstrating "no injury," "stable injury," or "unstable injury." Results were compared, and discrepancies between CT and MRI findings were noted. RESULTS: A total of 1,196 head-injured children were admitted to the pediatric intensive care unit between January 2002 and December 2012. Sixty-three children underwent CT and MRI and met Glasgow Coma Scale criteria. Seven children were identified with negative CT and positive MRI findings, but none of these injuries were considered unstable by our criteria. Five children were determined to have unstable injuries, and all were detected on CT. CONCLUSION: The results of this study suggest that MRI does not detect unstable CSIs in the setting of negative CT imaging. Given the limited patient population for this study, further and more extensive studies investigating the utility of MRI in the head-injured pediatric patient are warranted. LEVEL OF EVIDENCE: Diagnostic and care management study, level IV. PMID- 26151512 TI - Morphometric analysis of abdominal organs and rib cage: Implication for risk of solid organ injuries in children. AB - BACKGROUND: Motor vehicle crashes are the leading cause of injury-related mortality in children, with a higher rate of multiorgan injuries than in adults. This may be related to increased solid organ volume relative to abdominal cavity and decreased protection of an underdeveloped cartilaginous rib cage in young children. To date, these anatomic relationships have not been fully described. Our study used analytic morphomics to obtain precise measures of the pediatric liver, spleen, kidneys, and ribs. METHODS: This pilot study included 215 trauma patients (aged 0-18 years) with anonymized computed tomography (CT) scans. Liver, spleen, and kidney volumes were modeled using semiautomatic algorithms (MATLAB 2013a, MathWorks Inc., Natick, MA). Thirty-one scans were adequate to model the rib cage. Pearson's r was used to correlate absolute organ volume, fractional organ volume, and organ exposure with age and weight. RESULTS: Spleen, right and left kidney, and liver volumes increased with age and weight (p < 0.01). Right/left kidney and liver fractional volumes decreased with age (p < 0.01), whereas spleen fractional volume remained relatively constant. Exposed surface area of the liver only significantly decreased with age in the anterior (p < 0.01), right (p < 0.01), and posterior views (p = 0.02). DISCUSSION: With this study, we have demonstrated the ability to model solid organ and rib cage anatomy of children using cross-sectional imaging. In younger children, there may be a decrease in fractional organ volume and increase in liver surface exposure, although analysis of a larger sample size is warranted. In the future, this information may be used to improve the design of safety restraints in motor vehicles. PMID- 26151513 TI - Computed tomography-related radiation exposure in children transferred to a Level I pediatric trauma center. AB - PURPOSE: Pediatric trauma patients presenting to referring facilities (RF) often undergo computed tomography (CT) scans to identify injuries before transfer to a Level I pediatric trauma center (PTC). The purpose of our study was to evaluate RF compliance with the American College of Radiology (ACR) guidelines to minimize ionizing radiation exposure in pediatric trauma patients and to determine the frequency of additional or repeat CT imaging after transfer to a PTC. METHODS: After institutional review board approval, a retrospective review of all pediatric trauma admissions from January 2010 to December 2011 at our American College of Surgeons Level I PTC was performed. Patient demographics, means of arrival, Injury Severity Score, and disposition were analyzed. Patients who underwent CT were grouped by means of arrival: those who were transferred from an RF versus those who presented primarily to the PTC. Compliance with ACR guidelines and need for additional or repeat CT scans were assessed for both groups. RESULTS: Six hundred ninety-seven children (aged <18 years) were identified, with a mean age of 10.6 years. Three hundred twenty-one (46%) patients presented primarily to the PTC. Three hundred seventy-six (54%) were transferred from an RF, of which 90 (24%) patients underwent CT imaging before transfer. CT radiation dosing information was available for 79 (88%) of 90 patients. After transfer, 8 (9%) of 90 of children imaged at an RF required additional CT scans. In comparison, 314 (98%) of 321 patients who presented primarily to the PTC and underwent CT received appropriate pediatric radiation dosing. Mean radiation dose at PTC was approximately half of that at RF for CT scans of the head, chest, and abdomen/pelvis (p < 0.01). CONCLUSION: Pediatric trauma patients transferred from RF often undergo CT scanning with higher than recommended radiation doses, potentially placing them at an increased carcinogenic risk. Fortunately, few RF patients required additional CT scans after PTC transfer. Finally, compliance with ACR radiation dose limit guidelines is better achieved at a PTC. LEVEL OF EVIDENCE: Care management study, level IV. PMID- 26151514 TI - Nonpowder firearms cause significant pediatric injuries. AB - BACKGROUND: We hypothesize that nonpowder firearms cause significant injuries in children, often requiring intervention. We have noted a difference in demographics of children presenting with injuries from nonpowder firearms compared with patients injured by powder firearms. We reviewed our institution's experience with patients with nonpowder firearm injuries to evaluate these aspects. METHODS: A retrospective chart review was completed for all patients with a firearm injury from 2003 through February 2013 to a pediatric urban Level I trauma center. Patients were excluded if they were 18 years of age or older or readmitted. Demographics, injury circumstances, interventions, and outcomes were reviewed for 303 patients. The chi test and analysis of variance were completed with a statistical significance of p < 0.05. RESULTS: There were 57 nonpowder firearm injuries and 246 injuries from other firearms. Injuries occurred from BB, pellet, and paintball guns. Treatment included computed tomography scan in 39 patients, three bedside procedures, one angiography, and operative intervention in 25 patients. The most common injury locations were the eye (n = 37), head (n = 7), and neck (n = 6). Children injured by nonpowder firearms were less likely to be female (p = 0.04), more likely to be white (p < 0.01), and less likely to be injured in a violence-related event (p < 0.01). CONCLUSION: Nonpowder firearms can cause severe pediatric injuries requiring operative intervention and significant radiographic exposure from computed tomography scans. Prevention and education are important in decreasing this risk in the pediatric population and should be targeted to a different population than powder firearm prevention. LEVEL OF EVIDENCE: Epidemiologic study, level V. PMID- 26151515 TI - Injury patterns associated with hypotension in pediatric trauma patients: A national trauma database review. AB - BACKGROUND: Hypotension after trauma is most commonly assumed to be hemorrhagic, or hypovolemic, in origin. However, hypotension may occur in pediatric patients with isolated head injury, challenging accepted tenets of trauma care. We sought to quantify the contribution of head injury to the development of hypotension after pediatric trauma. METHODS: This is a retrospective cohort analysis using the National Trauma Data Bank registry 2009. Children aged 0 to 15 years were classified by injury pattern sustained during trauma using discharge diagnosis International Classification of Diseases, Ninth Revision, codes into isolated head, hemorrhagic, spinal cord, or other injury type. The primary outcome was hypotension for age at arrival to the emergency department. Risk of hypotension was estimated and compared by injury pattern using absolute and relative risks (RRs) stratified by age group (0-4 years, 5-11 years, 12-15 years). RESULTS: Rates of hypotension ranged from 1.8% to 2.3% by age, with the highest incidence in the 12- to 15-year group. The RR of hypotension from isolated head injury (RR, 2.5; 95% confidence interval, 2.0-3.2 vs. other) was not significantly different from the RR for hemorrhagic injury (RR, 2.7; 95% confidence interval, 2.1-3.5 vs. other) in the 0- to 4-year-old group. For the older age groups, the RR of hypotension from isolated head injury was significantly lower than from hemorrhagic injury. CONCLUSION: Hypotension occurs after isolated head injury in children, and the risk of hypotension is as great as hemorrhagic injuries in children aged 0 to 4 years. This finding should now lead us to confirm whether a cause-effect relationship exists and, if so, isolate the responsible mechanism. In turn, this could reveal an opportunity to tailor treatments to address the underlying mechanism for hypotension in these children. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26151516 TI - Hospital-acquired pneumonia among pediatric trauma patients treated at national trauma centers. AB - BACKGROUND: Injury is the leading cause of hospitalization in children, and as many as 5% of hospitalized injured children require mechanical ventilation. Despite this, little is known about the complications associated with mechanical ventilation, including pneumonia. METHODS: This is a retrospective analysis of trauma patients younger than 19 years from the National Trauma Data Bank from 2009 to 2011. Descriptive statistics were used to examine the patient population. Baseline characteristics were compared between subgroups using t tests and chi tests. Generalized linear models were used to identify risk factors for hospital acquired pneumonia adjusting for clustering of patients by hospital. RESULTS: A total of 252,187 patients were eligible for analysis, and 1,915 patients were diagnosed with pneumonia. Most patients were male (66.3%), were white (54.2%), had no comorbidities (88.9%), and were not considered severely injured (85.5% with an Injury Severity Score [ISS] < 16). The mean (SD) length of stay was 2.9 (5.2) days. Patients who developed pneumonia were older (16-18 years, 61.7% vs. 31.1%, p < 0.0001), had an increased length of stay (20.9 days vs. 2.8 days, p < 0.0001), more intensive care days (13.9 days vs. 0.7 days, p < 0.0001), and more ventilation days (9.5 days vs. 0.3 days, p < 0.0001) compared with those who did not develop pneumonia. The rate of pneumonia nearly doubled in patients spending 2 days on a ventilator (odds ratio [OR], 5.52; 95% confidence interval [CI], 3.45 8.84), doubled again for patients spending 3 days (OR, 10.59; 95% CI, 6.38 17.61), and doubled again for patients spending 5 days (OR, 23.72; 95% CI, 13.36 42.15) mechanically ventilated. The presence of two comorbid conditions was associated with twice the odds of developing pneumonia (OR, 2.10; 95% CI, 1.47 1.78). CONCLUSION: Prolonged mechanical ventilation, increased injury severity, older age, and presence of multiple comorbid conditions all increase the risk of pneumonia in injured children. Preventive measures should be aggressively used in injured children at high risk for the development of pneumonia. LEVEL OF EVIDENCE: Epidemiologic study, level III. PMID- 26151517 TI - Basal skull fractures are associated with mortality in pediatric severe traumatic brain injury. AB - BACKGROUND: Basal skull fractures (BSFs) are caused by blunt force trauma, occurring in the temporal, occipital, sphenoid, and/or ethmoid bones. In pediatric severe traumatic brain injury (sTBI), there is a paucity of data on BSFs. Our goal was to investigate the BSF prevalence, anatomy, and association with short-term outcomes in pediatric sTBI. METHODS: We retrospectively reviewed all severely injured (Injury Severity Score >=12) pediatric patients (aged <18 years) admitted to our hospital after experiencing an sTBI (Glasgow Coma Scale score <=8 and head Abbreviated Injury Scale score >=4). Neuroimaging for all sTBI patients was reviewed for skull fractures. Data were analyzed with both univariate and multivariate techniques. RESULTS: Of the 180 patients with sTBI, 47 had BSFs for a prevalence of 26% (69 BSFs in total; 16 sTBI patients had >=2 BSFs). The squamous temporal bone was fractured most frequently (n=30/47 sTBI patients with BSFs). Patients with BSFs were heavier and had more facial injuries than those without (p < 0.05) but were similar in all other admission demographics, injury profiles, and clinical characteristics. Cerebrospinal fluid leak was found in 32% (n = 15 of 47) of BSF patients (otorrhea, n = 12; rhinorrhea, n = 1; otorrhea/rhinorrhea, n = 2; p < 0.001). Mortality, acute central diabetes insipidus, and fewer ventilator-free days were associated with BSFs (p < 0.005), whereas in sTBI survivors, BSFs were associated with longer lengths of stay (p < 0.05). Multiple logistic regression showed that BSFs were positively associated with the presence of subarachnoid hemorrhage (odds ratio [OR], 4.00; p = 0.001), contusion (OR, 2.48; p = 0.029), herniation (OR, 3.40; p = 0.037), and cerebral edema (OR, 2.30; p = 0.047) but negatively associated with diffuse axonal injury (OR, 0.20; p = 0.003). BSFs and mortality were strongly associated (OR, 6.87; p = 0.019). CONCLUSION: BSFs occurred in 26% of pediatric sTBI patients. The temporal bone was fractured in two thirds of sTBI patients with BSFs, and one third was associated with cerebrospinal fluid leaks. BSFs represent a significant linear blunt force and are independent predictors of mortality. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26151518 TI - Correlation of computed tomographic signs of hypoperfusion and clinical hypoperfusion in adult blunt trauma patients. AB - BACKGROUND: The computed tomographic signs of hypoperfusion (CTSHs) have been reported in radiology literature as preceding the onset of clinical shock in children, but its correlation with tenuous hemodynamic status in adult blunt trauma patients has not been well studied. We hypothesized that these CT findings represent a clinically hypoperfused state and predict patient outcomes. METHODS: We retrospectively reviewed 52 adult blunt trauma patients who presented to our Level I trauma center with an Injury Severity Score (ISS) greater than 15 and a systolic blood pressure less than 90 mm Hg and who underwent torso CT scans during a period of 5.5 years. Patient's demographics and clinical data were recorded. All CT scans were assessed by our radiologist (J.M.) for 25 CTSHs. RESULTS: Seventy-nine percent of the patients studied exhibited CTSH. The mean number of signs identified per patient was 4. Patient with the most common CTSH, that is, free peritoneal fluid, small bowel enhancement, flattened inferior vena cava (IVC), and flattened renal veins, had a significantly higher intensive care unit admission rate than those without (all p < 0.05). Patient with signs of small bowel abnormal enhancement/dilation, flattened IVC/renal vein had worse acidosis (all p < 0.05). A significantly lower admission hemoglobin and an increased need for red blood cell transfusion were found in patient with flattened IVC (p < 0.05), flattened renal vein (p < 0.01), and active contrast extravasation (p < 0.01). Univariate analysis identified small bowel dilatation and splenic injury as factors associated with mortality and laparotomy, respectively. Logistic regression model revealed that splenic injury is a significant independent predictor of laparotomy (odd ratio, 7.50; 95% confidence interval, 1.67-33.71; p < 0.01). CONCLUSION: CTSH correlates with clinical hypoperfusion in blunt trauma patients and has important prognostic and therapeutic implications. The presence of CTSH in blunt trauma patients should draw immediate attention and require prompt intervention. Trauma surgeons should be familiar with these signs and include them in the clinical decision-making paradigms to improve outcomes in blunt trauma. LEVEL OF EVIDENCE: Diagnostic study, level III. PMID- 26151519 TI - Donabedian's structure-process-outcome quality of care model: Validation in an integrated trauma system. AB - BACKGROUND: According to Donabedian's health care quality model, improvements in the structure of care should lead to improvements in clinical processes that should in turn improve patient outcome. This model has been widely adopted by the trauma community but has not yet been validated in a trauma system. The objective of this study was to assess the performance of an integrated trauma system in terms of structure, process, and outcome and evaluate the correlation between quality domains. METHODS: Quality of care was evaluated for patients treated in a Canadian provincial trauma system (2005-2010; 57 centers, n = 63,971) using quality indicators (QIs) developed and validated previously. Structural performance was measured by transposing on-site accreditation visit reports onto an evaluation grid according to American College of Surgeons criteria. The composite process QI was calculated as the average sum of proportions of conformity to 15 process QIs derived from literature review and expert opinion. Outcome performance was measured using risk-adjusted rates of mortality, complications, and readmission as well as hospital length of stay (LOS). Correlation was assessed with Pearson's correlation coefficients. RESULTS: Statistically significant correlations were observed between structure and process QIs (r = 0.33), and process and outcome QIs (r = -0.33 for readmission, r = -0.27 for LOS). Significant positive correlations were also observed between outcome QIs (r = 0.37 for mortality-readmission; r = 0.39 for mortality-LOS and readmission-LOS; r = 0.45 for mortality-complications; r = 0.34 for readmission complications; 0.63 for complications-LOS). CONCLUSION: Significant correlations between quality domains observed in this study suggest that Donabedian's structure-process-outcome model is a valid model for evaluating trauma care. Trauma centers that perform well in terms of structure also tend to perform well in terms of clinical processes, which in turn has a favorable influence on patient outcomes. LEVEL OF EVIDENCE: Prognostic study, level III. PMID- 26151520 TI - Level I academic trauma center integration as a model for sustaining combat surgical skills: The right surgeon in the right place for the right time. AB - INTRODUCTION: As North Atlantic Treaty Organization (NATO) countries begin troop withdrawal from Afghanistan, military medicine needs programs for combat surgeons to retain the required knowledge and surgical skills. Each military branch runs programs at various Level I academic trauma centers to deliver predeployment training and provide a robust trauma experience for deploying surgeons. Outside of these successful programs, there is no system-wide mechanism for nondeploying military surgeons to care for a high volume of critically ill trauma patients on a regular basis in an educational environment that promotes continued professional development. We hypothesize that fully integrated military-civilian relationship regional Level I trauma centers provide a surgical experience more closely mirroring that seen in a Role III hospital than local Level II and Level III trauma center or medical treatment facilities. METHODS: We characterized the Level I trauma center practice using the number of trauma resuscitations, operative trauma/acute care surgery procedures, number of work shifts, operative density (defined as the ratio of operative procedures/days worked), and frequency of educational conferences. The same parameters were collected from two NATO Role III hospitals in Afghanistan during the peak of Operation Enduring Freedom. Data for two civilian Level II trauma centers, two civilian Level III trauma centers, and a Continental United States Military Treatment Facility without trauma designation were collected. RESULTS: The number of trauma resuscitations, number of 24-hour shifts, operative density, and educational conferences are shown in the table for the Level I trauma center compared with the different institutions. Civilian center trauma resuscitations and operative density were highest at the Level I trauma center and were only slightly lower than what was seen in Afghanistan. Level II and III trauma centers had lower numbers for both. The Level I trauma center provided the most frequent educational opportunities. CONCLUSION: In a Level I academic trauma center integrated program, military and civilian surgeons have the same clinical and educational responsibilities: rounding and operating, managing critical care patients, covering trauma/acute care surgery call, and mentoring surgery residents in an integrated residency program. The Level I trauma center experience most closely mimics the combat surgeon experience seen at NATO Role III hospitals in Afghanistan compared with other civilian trauma centers. At high-volume Level I trauma centers, military surgeons will have a comprehensive trauma practice, including dedicated educational opportunities. We recommend integrated programs with Level I academic trauma centers as the primary mechanism for sustaining military combat surgical skills in the future. PMID- 26151521 TI - National mandatory motorcycle helmet laws may save $2.2 billion annually: An inpatient and value of statistical life analysis. AB - BACKGROUND: While statistics exist regarding the overall rate of fatalities in motorcyclists with and without helmets, a combined inpatient and value of statistical life (VSL) analysis has not previously been reported. METHODS: Statistical data of motorcycle collisions were obtained from the Centers for Disease Control, National Highway Transportation Safety Board, and Governors Highway Safety Association. The VSL estimate was obtained from the 2002 Department of Transportation calculation. Statistics on helmeted versus nonhelmeted motorcyclists, death at the scene, and inpatient death were obtained using the 2010 National Trauma Data Bank. Inpatient costs were obtained from the 2010 National Inpatient Sample. Population estimates were generated using weighted samples, and all costs are reported using 2010 US dollars using the Consumer Price Index. RESULTS: A total of 3,951 fatal motorcycle collisions were reported in 2010, of which 77% of patients died at the scene, 10% in the emergency department, and 13% as inpatients. Thirty-seven percent of all riders did not wear a helmet but accounted for 69% of all deaths. Of those motorcyclists who survived to the hospital, the odds ratio of surviving with a helmet was 1.51 compared with those without a helmet (p < 0.001). Total costs for nonhelmeted motorcyclists were 66% greater at $5.5 billion, compared with $3.3 billion for helmeted motorcyclists (p < 0.001). Direct inpatient costs were 16% greater for helmeted riders ($203,248 vs. $175,006) but led to more than 50% greater VSL generated (absolute benefit, $602,519 per helmeted survivor). CONCLUSION: A cost analysis of inpatient care and indirect costs of motorcycle riders who do not wear helmets leads to nearly $2.2 billion in losses per year, with almost 1.9 times as many deaths compared with helmeted motorcyclists. The per capita cost per fatality is more than $800,000. Institution of a mandatory helmet law could lead to an annual cost savings of almost $2.2 billion. LEVEL OF EVIDENCE: Economic analysis, level III. PMID- 26151522 TI - Indications for use of damage control surgery and damage control interventions in civilian trauma patients: A scoping review. AB - BACKGROUND: Variation in the use of damage control (DC) surgery across trauma centers may partially be driven by uncertainty as to when the procedure is indicated. We sought to scope the literature on DC surgery and DC interventions, identify their reported indications, and examine the content and evidence upon which they are based. METHODS: We searched MEDLINE, EMBASE, PubMed, Scopus, Web of Science, and the Cochrane Library (1950-February 14, 2014) and the grey literature for original and nonoriginal citations reporting indications for DC surgery or DC interventions in civilian trauma patients. RESULTS: Among 27,732 citations identified, we included 270 peer-reviewed articles in the scoping review. Of these, 156 (57.8%) represented original research, primarily (75.0%) cohort studies. The articles reported 1,099 indications for DC surgery and 418 indications for 15 different DC interventions. The majority of indications for DC interventions were for abdominal (56.5%) procedures, including therapeutic perihepatic packing (56.5%), temporary abdominal closure/open abdominal management (40.7%), and staged pancreaticoduodenectomy (2.8%). Most DC surgery indications were based on intraoperative findings (71.7%) and represented characteristics of the injured patient (94.5%), including their physiology (57.6%), injuries (38.9%), and/or the amount or type of resuscitation provided (14.3%). Others were dependent on characteristics of the treating surgeon (12.1%), the patient's physiologic response to trauma care (9.6%), and/or the trauma care environment (1.5%). Approximately half (49.5%) included a decision threshold (e.g., pH < X) and, while most (74.7%) were based on a single clinical finding/injury, 25.3% required the presence of multiple findings concurrently. Only 87 indications were evaluated in original research studies and only 9 by more than one study. CONCLUSION: The vast number, varying underlying content, and lack of original research relating to indications for DC suggests that substantial uncertainty exists around when the procedure is indicated and highlights the need to establish evidence-informed consensus indications. PMID- 26151524 TI - Review of short-term outcomes for TEVAR after blunt traumatic aortic injury. PMID- 26151525 TI - Futility and the acute care surgeon. PMID- 26151523 TI - Injury in the aged: Geriatric trauma care at the crossroads. PMID- 26151526 TI - 2014 Consensus conference on viscoelastic test-based transfusion guidelines for early trauma resuscitation: Report of the panel. AB - There has been an increased interest in the use of viscoelastic testing to guide blood product replacement during the acute resuscitation of the injured patient. Currently, no uniformly accepted guidelines exist for how this technology should be integrated into clinical care. In September 2014, an international multidisciplinary group of leaders in the field of trauma coagulopathy and resuscitation was assembled for a 2-day consensus conference in Philadelphia, Pennsylvania. This panel included trauma surgeons, hematologists, blood bank specialists, anesthesiologists, and the lay public.Nine questions regarding the impact of viscoelastic testing in the early resuscitation of trauma patients were developed before the conference by panel consensus. Early use was defined as baseline viscoelastic test result thresholds obtained within the first minutes of hospital arrival-when conventional laboratory results are not available. The available data for each question were then reviewed in person using standardized presentations by the expert panel. A consensus summary document was then developed and reviewed by the panel in an open forum. Finally, a two-round Delphi poll was administered to the panel of experts regarding viscoelastic thresholds for triggering the initiation of specific treatments including fibrinogen, platelets, plasma, and prothrombin complex concentrates. This report summarizes the findings and recommendations of this consensus conference. PMID- 26151527 TI - Sharp lower abdominal pain and calcified abdominal mass. PMID- 26151528 TI - Re: Critique on hyperglycemia and surgical site infection. PMID- 26151529 TI - Association of emergency general surgery with excess postoperative morbidity and mortality. PMID- 26151530 TI - Re: Association of emergency general surgery with excess postoperative morbidity and mortality. PMID- 26151531 TI - Routine whole-body computed tomography in major trauma resuscitation: From "donut of death" to "do not without"? PMID- 26151532 TI - Re: Routine whole-body computed tomography in major trauma resuscitation: From "donut of death" to "do not without"? PMID- 26151533 TI - Hemostatic resuscitation is neither hemostatic nor resuscitative in trauma hemorrhage-But did they in fact test the effect of hemostatic resuscitation? PMID- 26151534 TI - Re: Hemostatic resuscitation is neither hemostatic nor resuscitative in trauma hemorrhage: But did they in fact test the effect of hemostatic resuscitation? PMID- 26151537 TI - Phytoremediation of Water Using Phragmites karka and Veteveria nigritana in Constructed Wetland. AB - Constructed wetland is an innovative and emerging ecological technology for wastewater treatment. This study was conducted to investigate the effectiveness of a Vegetated Submerged Bed Constructed Wetland (VSBCW) for removal of heavy metals from industrial wastewater in a steel manufacturing company. A pilot Effluent Treatment Plant (ETP) consisting of equalization basin, two VSBCW basins and a storage tank was constructed. The VSBCW was constructed using 10-30 mm round granite for the different zones. This was overlaid by 200 mm deep granite and 150 mm washed sand with Phragmites karka, Vetiveria nigritana and Cana lilies as macrophytes. Irrigation of macrophytes using effluent from the industry was done after 3 months of planting and ETP monitored. Industrial wastewater samples were collected and analyzed for heavy metals such as zinc (Zn), lead (Pb), iron (Fe), manganese (Mn), magnesium (Mg) and chromium (Cr) to know the treatment efficiency of the ETP. Results indicated that the removal efficiencies of the VSBCW for Pb, Mg and Cr were 15.4%, 79.7% and 97.9% respectively. Fe and Mn were seen to increase by 1.8% and 33% respectively. The ETP using locally available macrophytes is effective in the phytoremediation of heavy metals, particularly Cr from the wastewater. PMID- 26151538 TI - Near-Infrared Lasing from Small-Molecule Organic Hemispheres. AB - Near-infrared (NIR) lasers are key components for applications, such as telecommunication, spectroscopy, display, and biomedical tissue imaging. Inorganic III-V semiconductor (GaAs) NIR lasers have achieved great successes but require expensive and sophisticated device fabrication techniques. Organic semiconductors exhibit chemically tunable optoelectronic properties together with self-assembling features that are well suitable for low-temperature solution processing. Major blocks in realizing NIR organic lasing include low stimulated emission of narrow-bandgap molecules due to fast nonradiative decay and exciton exciton annihilation, which is considered as a main loss channel of population inversion for organic lasers under high carrier densities. Here we designed and synthesized the small organic molecule (E)-3-(4-(di-p-tolylamino)phenyl)-1-(1 hydroxynaphthalen-2-yl)prop-2-en-1-one (DPHP) with amphiphilic nature, which elaborately self-assembles into micrometer-sized hemispheres that simultaneously serves as the NIR emission medium with a photoluminescence quantum efficiency of ~15.2%, and the high-Q (~1.4 * 10(3)) whispering gallery mode microcavity. Moreover, the radiative rate of DPHP hemispheres is enhanced up to ~1.98 * 10(9) s(-1) on account of the exciton-vibrational coupling in the solid state with the J-type molecular-coupling component, and meanwhile the exciton-exciton annihilation process is eliminated. As a result, NIR lasing with a low threshold of ~610 nJ/cm(2) is achieved in the single DPHP hemisphere at room temperature. Our demonstration is a major step toward incorporating the organic coherent light sources into the compact optoelectronic devices at NIR wavelengths. PMID- 26151539 TI - Li7(BH)5(+): a new thermodynamically favored star-shaped molecule. AB - The potential energy surfaces (PESs) of Lin(BH)5(n-6) systems (where n = 5, 6, and 7) were explored using the gradient embedded genetic algorithm (GEGA) program, in order to find their global minima conformations. This search predicts that the lowest-energy isomers of Li6(BH)5 and Li7(BH)5(+) contain a (BH)5(6-) pentagonal fragment, which is isoelectronic and structurally analogous to the prototypical aromatic hydrocarbon anion C5H5(-). Li7(BH)5(+), along with Li7C5(+), Li7Si5(+) and Li7Ge5(+), joins a select group of clusters that adopt a seven-peak star-shape geometry, which is favored by aromaticity in the central five-membered ring, and by the preference of Li atoms for bridging positions. The theoretical analysis of chemical bonding, based on magnetic criteria, supports the notion that electronic delocalization is an important stabilization factor in all these star-shaped clusters. PMID- 26151540 TI - MicroRNA-197 reverses the drug resistance of fluorouracil-induced SGC7901 cells by targeting mitogen-activated protein kinase 1. AB - MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which serve an important function in the development of multidrug resistance in cancer through the post-transcriptional regulation of gene expression and RNA silencing. In the present study, the functional effects of miR-197 were analyzed in chemo-resistant gastric cancer cells. Low expression levels of miR-197 were observed in the fluorouracil (5-FU)-resistant gastric cell line SGC7901/5-FU when compared with those in the parental gastric cell line SGC7901. Overexpression of miR-197 in SGC7901/5-FU cells was identified to partially restore 5-FU sensitivity. miRNA target prediction algorithms suggested that mitogen-activated protein kinase 1 (MAPK1) is a candidate target gene for miR-197. A luciferase reporter assay confirmed that miR-197 led to silencing of the MAPK1 gene by recognizing and then specifically binding to the predicted site of the MAPK1 mRNA 3'-untranslated region. When miR-197 was overexpressed in SGC7901 cells, the protein levels of MAPK1 were downregulated. Furthermore, MAPK1 knockdown significantly increased the growth inhibition rate of the SGC7901/5-FU cells compared with those in the control group. These results indicated that miR-197 may influence the sensitivity of 5-FU treatment in a gastric cancer cell line by targeting MAPK1. PMID- 26151542 TI - Exclusive Hydrophobic Self-Assembly of Adaptive Solid-State Networks of Octasubstituted 9,9'-Spirobifluorenes. AB - An easy and powerful access to 3,3',6,6'-tetrasubstituted 9,9'-spirobifluorene derivatives with tetrahedral orientation of the peripheral groups (i.e., -I, -CN, -NO2, -CH?O, -COOH, -C=CH, -4-Py) was developed. The NMR and HRMS results are in agreement with the proposed formula and the solid-state molecular structures obtained by single-crystal X-ray diffraction. They form molecular solids self assembled via exclusive hydrophobic interactions. Solid-state selection and adaptation can be obtained on the basis of variable compact packing of functional groups present on the 9,9'-spirobifluorene backbone. PMID- 26151543 TI - Current status of Bacille Calmette Guerin (BCG) immunisation in Europe - A ptbnet survey and review of current guidelines. AB - BACKGROUND: The incidence of tuberculosis (TB) and the use of Bacille Calmette Guerin (BCG) vaccines differ significantly worldwide. Information regarding recent changes in BCG use and immunisation policies is difficult to access. Therefore, this study aimed to systematically collect up-to-date data on the use of BCG in Europe. METHODS: A web-based survey of members of the Paediatric Tuberculosis Network European Trials group (ptbnet) and Tuberculosis Network European Trials group (TBnet) was conducted between October 2012 and May 2013. RESULTS: A total of 89 individuals from 31 European countries participated. Participants from 27/31 (87%) countries reported to have a national BCG immunisation policy/guideline. Reported indications for BCG immunisation were: universally at birth (14/31; 45%), universally at older age (2/31; 6%), at birth for high-risk groups (12/31; 39%), at older age for high-risk groups (6/31; 19%), at older age for Mantoux-negative individuals (6/31;19%), for immigrants (4/31; 13%) and as a travel vaccine (10/31; 32%). Members from 11 (35%) countries reported changes in BCG policies in the previous 5 years: discontinuation of universal immunisation of infants/children (6/11), reintroduction of immunisation of high-risk children (3/11), and change in BCG vaccine strain (2/11). Members from 24/31 (77%) countries reported using BCG Denmark. CONCLUSIONS: Immunisation policies regarding BCG vaccine exist in the majority of European countries. Indications for BCG immunisation varied considerably, likely reflecting national TB incidence rates, immigration and other factors influencing TB control strategies. Importantly, the considerable number of recent policy changes highlights the need for regular collection of up-to-date information to inform public health planning. PMID- 26151544 TI - Vaccinations in sickle cell disease: An audit of vaccination uptake in sickle cell patients attending Newham University Hospital. AB - AIMS: To assess the level of adherence of patients with sickle cell disease to the advised vaccination schedule with respect to the Sickle Cell Society guidelines on vaccination [1,2]. METHODS: A retrospective audit of patients' vaccination records was carried out between July 2012 and June 2013 on a sample of 80 patients over the age of 16, who attended Newham University Hospital accident and emergency (A&E) department with a presenting complaint coded as "sickle cell". A re-audit was conducted from January 2014 to December 2014 to close the audit loop. Chi-squared and Fisher's exact tests were used to compare the results. RESULTS: The initial audit and re-audit identified 80 and 86 patients, respectively. Only 2 (2012-2013) and 7 (2014) patients had a complete up-to-date vaccination profile. 24 (30%) patients had up-to-date influenza vaccination, increasing to 43 (50%, P=0.0062) when re-audited. 33 (41%) had current pneumococcal vaccinations, increasing to 38 (44%, P=0.7874). Uptake rates for vaccinations against Meningococcal group C (MenC), Haemophilus influenzae B (HiB) and Hepatitis B virus (HBV) were under 31% in both audits. A significant improvement in vaccination rate was observed for all vaccinations except pneumococcal and HBV. CONCLUSIONS: Although significant improvements have been demonstrated, this audit shows a low level of adherence to the advised vaccination schedule. The study also highlighted a shortfall in appropriate record keeping, reducing the potential for detailed conclusions being drawn in relation to the childhood vaccinations against MenC, HiB and HBV. Implementation of a new database of vaccination history, raising GP awareness and patient education seminars has lead to a significant improvement in vaccination rates locally and the authors hope that this may be replicated in other centres. There may be potential to increase rates further by administering vaccinations to inpatients. PMID- 26151545 TI - A history of the DNA repair and mutagenesis field: I. The discovery of enzymatic photoreactivation. AB - Photoreactivation, an enzyme-catalyzed reaction during which two covalently linked pyrimidine dimers in DNA are monomerized and restored to their native conformation was the first DNA repair mechanism to be discovered, an event that transpired in the late 1940's through the efforts of the American biologist Albert Kelner while at the Cold Spring Harbor Laboratories in upstate New York. The phenomenon was Independently observed by Renato Dulbecco shortly thereafter, then a post-doctoral fellow in Salvador Luria's Laboratory in Bloomington Indiana. However, Luria and Dulbecco yielded priority to Kelner's discovery. PMID- 26151546 TI - Fluorescence switching method for cascade detection of salicylaldehyde and zinc(II) ion using protein protected gold nanoclusters. AB - A new fluorescence switching sensor for cascade detection of salicylaldehyde (SA) and Zinc(II) ion was developed based on bovine serum albumin protected gold nanoclusters (BSA-AuNCs). In the detection, SA interacted with amino groups of BSA-AuNCs, inducing simultaneous formation of fluorescent Schiff base and fluorescence quenching of AuNCs. Zn(II) could further strongly coordinate with the Schiff base ligands, leading to blue-shift and increase of the fluorescence from Schiff base-metal coordination complexes and simultaneous recovery of fluorescence from AuNCs. The new fluorescence switching sensor for Zn(2+) detection has advantages of simplicity, rapidity, naked-eye detection, high sensitivity and selectivity. The linear range of the method for Zn(2+) detection is from 0.1 MUM to 100 MUM with the limit of detection (LOD) of 29.28 nM. In practical samples, the recoveries of the samples ranged from 99.63% to 100.58%. PMID- 26151547 TI - Fiber-optic immunosensor for detection of Crimean-Congo hemorrhagic fever IgG antibodies in patients. AB - Crimean-Congo hemorrhagic fever (CCHF) is a severe viral disease with high fatality rate. CCHF virus is endemic in parts of Africa, Asia, the Middle East, and southeastern Europe. Rapid diagnostics of CCHF is vital for appropriate clinical management and prevention of secondary spread from human-to-human. Currently, diagnostics relies on real-time RT-PCR and antibody or antigen detection using ELISA. These methods require trained personnel and expensive equipment and are not appropriate for point-of-care (POC) diagnostics. Furthermore, there are no POC assays available for CCHF. We developed a fiber optic biosensor for the detection of CCHF IgG antibodies. In order to improve sensitivity, we optimized both the bioreceptor immobilization protocol and the chemiluminescence substrate formulation. The resulting protocol showed a 100-fold greater sensitivity for detection of CCHF antibodies. Finally, we evaluated the fiber-optic biosensor with two CCHF patient sera. We showed that the fiber-optic biosensor is 10-times more sensitive than colorimetric ELISA and is able to detect both patients with high and low levels of IgG antibodies. We believe that the fiber-optic biosensor is a suitable alternative to ELISA as it is much more sensitive and makes it possible to detect a small amount of antibodies at an early stage of infection and can be integrated as a point-of-care diagnostic system of CCHF. PMID- 26151549 TI - Photoresponsive self-assembled hexameric capsules based on calix[4]resorcinarenes bearing azobenzene dendron conjugates as side chains. AB - We synthesized calix[4]resorcinarenes bearing various azobenzene dendron conjugates as side chains, wherein the azobenzene moiety is a photoresponsive unit and the dendron moiety is a capsule-destabilizing unit, and then studied the photoresponsive properties of their self-assembled hexameric capsules in conjunction with guest encapsulation in H2O-saturated CDCl3. It was found that correlation between the trans-to-cis photoisomerization of the azobenzene dendron side chains of hosts and the consequent capsule destabilization leading to guest release largely depends on the nature of the dendron moieties, such as their steric bulkiness or hydrophilicity. PMID- 26151548 TI - Harmaline and hispidin from Peganum harmala and Inonotus hispidus with binding affinity to Candida rugosa lipase: In silico and in vitro studies. AB - The inhibitory effect of phenolic compounds and alkaloids of Inonotus hispidus and Peganum harmala on Candida rugosa lipase was investigated, also, their antioxidant activities using DPPH, ABTS and phosphomolybdenum were studied in this paper. The phenolic extracts have shown a stronger antiradical activity than the alkaloids extracts. The enzymatic inhibition produced by these extracts is described here for the first time. The results have shown that the phenolic and the alkaloid extracts are good inhibitors of C. rugosa lipase. Thus, the inhibitor molecules (harmaline and hispidin) have been isolated from P. harmala and I. hispidus. Their structures were elucidated by (1)H NMR analysis. Molecular docking has been achieved using AutoDock Vina program to discuss the nature of interactions and the mechanism of inhibition. Therefore, these isolated molecules could be used in the treatment of candidiasis. PMID- 26151550 TI - Heavily Doped, Charge-Balanced Fluorescent Organic Light-Emitting Diodes from Direct Charge Trapping of Dopants in Emission Layer. AB - We studied the effect of direct charge trapping at different doping concentrations on the device performance in tris(8-hydroxyquinoline) aluminum (Alq3):10-(2-benzothiazolyl)-2,3,6,7-tetrahydro-1,1,7,7-tetramethyl-1H,5H,11H-(1) benzopyropyrano(6,7-8-i,j)quinolizin-11-one (C545T) as a host-dopant system of a fluorescent organic light-emitting diode. With increasing C545T doping concentration, trap sites could lead to the promotion of hole injection and the suppression of electron injection due to the electron-transport character of Alq3 host for each carriers, as confirmed by hole- and electron-only devices. Direct charge injection of hole carriers from the hole transport layer into C545T dopants and the charge trapping of electron carriers are the dominant processes to improve the charge balance and the corresponding efficiency. The shift of the electroluminescence (EL) spectra from 519 nm to 530 nm was confirmed the exciton formation route from Forster energy transfer of host-dopant system to direct charge trapping of dopant-only emitting systems. Variation in the doping concentration dictates the role of the dopant in the fluorescent host-dopant system. Even though concentration quenching in fluorescent dopants is unavoidable, relatively heavy doping is necessary to improve the charge balance and efficiency and to investigate the relationship between direct charge trapping and device performance. Heavy doping at a doping ratio of 6% also generates heavy exciton quenching and excimer exciton, because of the excitons being close enough and dipole-dipole interactions. The optimum device performance was achieved with a 4%-doped device, retaining the high efficiency of 12.5 cd/A from 100 cd/m(2) up to 15,000 cd/m(2). PMID- 26151551 TI - Prenatal whole-exome sequencing: parental attitudes. AB - OBJECTIVE: The aim of this study was to survey the opinions of expectant parents regarding prenatal whole-exome sequencing. METHODS: The study used a questionnaire that focused on acceptability of prenatal whole-exome sequencing to individuals who pursued first-trimester prenatal screening in a tertiary academic medical center. A total of 186 expectant individuals completed the questionnaire. The results of the questionnaire were analyzed using descriptive statistics and logistic regression models. RESULTS: Eighty-three percent of the participants answered that prenatal whole-exome sequencing should be offered, 14.8% were neutral, and only 2.2% disagreed. Fifty-four percent of the participants were interested in having prenatal whole-exome sequencing for their fetus, 40.1% were neutral, and 6.6% disagreed. The majority of participants expressed a desire to know about treatable (96.2%) and non-treatable (86.3%) childhood conditions, and most said the same for treatable (76.0%) and non-treatable (74.3%) adult-onset conditions. Over half of the participants (59.7%) indicated a maximum acceptable turnaround time of 3 weeks or less for prenatal whole-exome sequencing. CONCLUSIONS: The majority of respondents felt prenatal whole-exome sequencing should be offered. Moreover, the majority wanted to know prenatally about treatable and non-treatable childhood and adult conditions. PMID- 26151552 TI - Atomistic Molecular Insight into the Time Dependence of Polymer Glass Transition. AB - The most atomistic molecular details of polymer glass transition were analyzed through the frozen torsions in our molecular dynamics simulations. Different observation times were used to determine the frozen fractions and frozen chain lengths. The glass transition temperature was found to coincide well with the temperature at which the frozen fractions were reduced to 1/e. The frozen chain segments grow as the temperature decreases in a similar way with that of linear polymerization, and the inverse number-average frozen chain length leads to the formulation of configuration entropy during glass transition. The ideal glass transition temperature extrapolated to zero configuration entropy corresponds well with those reported in the literature, and the relation between the relaxation time and the configuration entropy shows perfect agreement with the Adam-Gibbs theory around the glass transition temperature. Volume spanning clusters are formed at the low temperature end, which might serve as a premature prototype for the formation of the "ideal glassy state" with limited accessible configurations. PMID- 26151553 TI - Developmental potential of 2n/3n mixoploid mouse embryos produced by fusion of individual second polar bodies and blastomeres of 2-cell embryos. AB - Using 2n/3n mixoploid mouse embryos produced by fusion of individual second polar bodies (PB2s) with individual blastomeres of 2-cell embryos, the dynamics of PB2 nuclei in the host blastomeres during mitosis were examined and the fate of the 3n cell line in the mixoploid embryos was followed. Most of the PB2 nuclei were synchronised with the cell cycle of the host blastomeres and all chromosomes were incorporated into a single mitotic spindle. The majority of the mixoploid embryos developed to blastocysts with 3n cells. In conceptuses at Day 11.5 and Day 18.5 of gestation, 3n cells were recognised in both of the embryonic/fetal and placental tissues. When green fluorescent protein (GFP)-transgenic mice were used as a donor of PB2, GFP-positive 3n cells were found in more than 40% of morulae and blastocysts, indicating that the PB2 genome can be reactivated during the pre implantation stage. GFP-positive 3n cells were non-randomly allocated in trophectoderm in blastocysts. These findings may explain the production mechanism of 2n/3n mixoploid human embryos, that is, a PB2 is incorporated into one daughter blastomere during the early cleavage period. PMID- 26151554 TI - Chronic Replication Problems Impact Cell Morphology and Adhesion of DNA Ligase I Defective Cells. AB - Moderate DNA damage resulting from metabolic activities or sub-lethal doses of exogenous insults may eventually lead to cancer onset. Human 46BR.1G1 cells bear a mutation in replicative DNA ligase I (LigI) which results in low levels of replication-dependent DNA damage. This replication stress elicits a constitutive phosphorylation of the ataxia telangiectasia mutated (ATM) checkpoint kinase that fails to arrest cell cycle progression or to activate apoptosis or cell senescence. Stable transfection of wild type LigI, as in 7A3 cells, prevents DNA damage and ATM activation. Here we show that parental 46BR.1G1 and 7A3 cells differ in important features such as cell morphology, adhesion and migration. Comparison of gene expression profiles in the two cell lines detects Bio Functional categories consistent with the morphological and migration properties of LigI deficient cells. Interestingly, ATM inhibition makes 46BR.1G1 more similar to 7A3 cells for what concerns morphology, adhesion and expression of cell-cell adhesion receptors. These observations extend the influence of the DNA damage response checkpoint pathways and unveil a role for ATM kinase activity in modulating cell biology parameters relevant to cancer progression. PMID- 26151556 TI - Urban particulate matter increases human airway epithelial cell IL-1beta secretion following scratch wounding and H1N1 influenza A exposure in vitro. AB - PURPOSE: The airway epithelium represents the first line of defense against inhaled environmental insults including air pollution, allergens, and viruses. Epidemiological and experimental evidence has suggested a link between air pollution exposure and the symptoms associated with respiratory viral infections. We hypothesized that multiple insults integrated by the airway epithelium NLRP3 inflammasome would result in augmented IL-1beta release and downstream cytokine production following respiratory virus exposure. MATERIALS AND METHODS: We performed in vitro experiments with a human airway epithelial cell line (HBEC 6KT) that involved isolated or combination exposure to mechanical wounding, PM10, house dust mite, influenza A virus, and respiratory syncytial virus. We performed confocal microscopy to image the localization of PM10 within HBEC-6KT and ELISAs to measure soluble mediator production. RESULTS: Airway epithelial cells secrete IL-1beta in a time-dependent fashion that is associated with internalization of PM10 particles. PM10 exposure primes human airway epithelial cells to subsequent models of cell damage and influenza A virus exposure. Prior PM10 exposure had no effect on IL-1beta responses to RSV exposure. Finally we demonstrate that PM10 priming of human airway epithelial cell IL-1beta and GM-CSF responses to influenza A exposure are sensitive to NLRP3 inflammasome inhibition. CONCLUSIONS: Our results suggest the NLRP3 inflammasome may contribute to exaggerated immune responses to influenza A virus following periods of poor air quality. Intervention strategies targeting the NLRP3 inflammasome in at risk individuals may restrict poor air quality priming of mucosal immune responses that result from subsequent viral exposures. PMID- 26151555 TI - Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection. AB - The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naive female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5 yrs were more frequently female (59%; p<0.001). Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively). However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001). The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above threshold CD4 counts (p=0.002). These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex. PMID- 26151557 TI - Convergent Reduction of Ovariole Number Associated with Subterranean Life in Beetles. AB - BACKGROUND: Some species of obligate cavernicolous beetles are known to possess a unique feature-a contraction of the larval cycle. In contrast to many other subterranean beetles, life-cycle contraction in Trechini ground beetles (Carabidae) is correlated with a reduction in the number of eggs and a drastic reduction in the number of ovarioles. This remarkable peculiarity has only been reported for a small number of closely related species. RESULTS: We give a description of the female internal reproductive system for six species of Trechini, including five subterranean species, with a particular focus on the western Pyrenean radiation of Aphaenops, a group for which nothing is known regarding the early life stages. We redescribe the internal female genitalia of A. crypticola Linder. Study of the ovarioles allowed us to infer the postembryonic development of the larvae for each species examined. We then used a phylogenetic framework to recognize two independent reductions in the number of ovarioles in the Pyrenean lineage. We discuss the multiple convergent evolutions in ovariole number and the potential link between a reduction of ovariole number and troglobiomorphism in a phylogenetic context. CONCLUSIONS: There is an extreme reduction in ovariole number and size within the species studied; the eggs produced by small ovarioles have a remarkably large size. A reduction to one ovariole has occurred independently at least twice in this subterranean group. A reduction in the number of ovarioles in ground beetles is one of the striking consequences of subterranean specialization and it is correlated with another remarkable adaptation of subterranean beetles, a reduction in the number of larval instars. PMID- 26151558 TI - Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis. AB - A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV 6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied. PMID- 26151561 TI - Permissive parenting and mental health in college students: Mediating effects of academic entitlement. AB - OBJECTIVE: Student mental health may suffer due to unreasonable expectations associated with academic entitlement; permissive parenting may be one source of these expectations. The authors examined the role of academic entitlement as a mediator of the relationship between permissive parenting and psychological functioning. PARTICIPANTS: Participants were 524 undergraduate students at a single institution (52% female; age range = 18-22). Data collection was completed in May 2011. METHODS: Cross-sectional design. Participants completed online self report measures of parenting styles, academic entitlement, stress, depressive symptoms, and well-being. RESULTS: Permissive parenting was associated with greater academic entitlement and, in turn, to more perceived stress and poorer mental health. Mother/father differences were found in some cases. CONCLUSIONS: Academic entitlement may partially explain why permissive parenting is detrimentally related to mental health for college students. Implications for academic affairs and counseling include helping students develop an appreciation of the role of self-regulation in college success. PMID- 26151560 TI - Dispersal Mutualism Incorporated into Large-Scale, Infrequent Disturbances. AB - Because of their influence on succession and other community interactions, large scale, infrequent natural disturbances also should play a major role in mutualistic interactions. Using field data and experiments, I test whether mutualisms have been incorporated into large-scale wildfire by whether the outcomes of a mutualism depend on disturbance. In this study a seed dispersal mutualism is shown to depend on infrequent, large-scale disturbances. A dominant shrubland plant (Arctostaphylos species) produces seeds that make up a persistent soil seed bank and requires fire to germinate. In post-fire stands, I show that seedlings emerging from rodent caches dominate sites experiencing higher fire intensity. Field experiments show that rodents (Perimyscus californicus, P. boylii) do cache Arctostaphylos fruit and bury most seed caches to a sufficient depth to survive a killing heat pulse that a fire might drive into the soil. While the rodent dispersal and caching behavior itself has not changed compared to other habitats, the environmental transformation caused by wildfire converts the caching burial of seed from a dispersal process to a plant fire adaptive trait, and provides the context for stimulating subsequent life history evolution in the plant host. PMID- 26151559 TI - The Association between Newborn Regional Body Composition and Cord Blood Concentrations of C-Peptide and Insulin-Like Growth Factor I. AB - BACKGROUND: Third trimester fetal growth is partially regulated by C-peptide and insulin-like growth factor I (IGF-I). Prenatal exposures including maternal obesity and high gestational weight gain as well as high birth weight have been linked to subsequent metabolic disease. We evaluated the associations between newborn regional body composition and cord blood levels of C-peptide and IGF-I. METHODS: We prospectively included obese and normal-weight mothers and their newborns; cord blood was collected and frozen. Analyses of C-peptide and IGF-I were performed simultaneously, after recruitment was completed. Newborn regional body composition was assessed with dual-energy X-ray absorptiometry scanning (DXA) within 48 hours of birth. RESULTS: Three hundred thirty-six term infants were eligible to participate in the study; of whom 174 (52%) infants had cord blood taken. Total, abdominal and arm and leg fat mass were positively associated with C-peptide (p < 0.001). Arm and leg fat mass was associated with IGF-I concentration: 28 g [95% confidence interval: 4, 53] per doubling of IGF-I. There was no association between total or abdominal fat mass and IGF-I. Fat-free mass was positively associated with both C-peptide (p < 0.001) and IGF-I (p = 0.004). CONCLUSION: Peripheral fat tissue accumulation was associated with cord blood C peptide and IGF-I. Total and abdominal fat masses were related to C-peptide but not to IGF-I. Thus, newborn adiposity is partially mediated through C-peptide and early linear growth is associated with IGF-I. PMID- 26151562 TI - Cortactin promotes colon cancer progression by regulating ERK pathway. AB - Cortactin is upregulated in various cancers including breast cancer, head and neck squamous cell carcinoma and gastric cancer. However, the role of cortactin in the pathogenesis of colon cancer remains unclear. mRNA expression of cortactin in colon cancer samples and cell lines was detected by quantitative real-time PCR (qRT-PCR), while protein expression of cortactin in colon cancer tissues and adjacent non-cancer tissues was assessed by immunohistochemistry. The role of cortactin in regulation of the proliferation of colon cancer derived cells were investigated both in vitro and in vivo. In the total of 60 paired colon cancer specimens, compared with the adjacent non-cancer tissues, the expression of cortactin mRNA was upregulated in 45 (75.0%). Immunohistochemical analysis showed significantly increased cortactin expression in colon cancer (42/60, 70.0%) compared to control tissues (18/60, 30.0%). Overexpression of cortactin promoted HCT116 cellular colony formation and tumor growth. Conversely, cortactin knockdown inhibited these effects in SW480 cells. Mechanistic analyses indicated that cortactin was able to activate the EGFR-ERK signaling pathway. Additionally, cortactin expression was associated with tumor size, tumor stages and lymphatic invasion, increased cortactin expression predicts poor prognosis in patients with colon cancer. In summary, cortactin demonstrated the promotive effect in human colon cancer cell growth and tumorigenicity. These results indicated that cortactin may serve as an effective target for gene therapy. PMID- 26151563 TI - Spectrophotometric Evaluation of Potassium Nitrate Penetration Into the Pulp Cavity. AB - OBJECTIVES: The aim of this study was to evaluate the penetration level of potassium nitrate-containing desensitizers or whitening materials into the pulp cavity with regard to the concentration and viscosity of the formulation. METHODS AND MATERIALS: Fifty extracted human molar teeth were prepared and randomized into five groups of 10 specimens each. The control received a 30-minute treatment without any treatment material; the other four groups corresponded to treatment with DayWhite, a 14% hydrogen peroxide whitening material containing potassium nitrate; PreviDent 5000 Sensitive, a desensitizing toothpaste; Relief ACP, a desensitizing gel; or UltraEZ, a desensitizing gel. Potassium nitrate penetration levels were measured spectrophotometrically based on the Griess assay method. Treatment materials were measured for viscosity as a function of shear rate through the use of a cone-and-plate rheometer. RESULTS: Nitrate penetration levels were significantly different among the five groups (p<0.0001, Kruskal Wallis test). After adjustment for multiple comparisons using an overall 0.05 level of type I error, the distribution of nitrate penetration values was found to differ significantly among all groups with the exception of DayWhite (median: 10.72 MUM) and UltraEZ (median: 9.22 MUM), which differed significantly from other groups but not from each other. The highest levels of nitrate penetration value were observed for PreviDent (median: 27.61 MUM) followed by Relief ACP (median: 19.64 MUM). The lowest penetration level was observed for the control group (median: 3.41 MUM). Stable end-point viscosities of 11.43 +/- 0.67 Pa/s, 1.33 +/- 0.06 Pa/s, 0.85 +/- 0.09 Pa/s, and 0.40 +/- 0.01 Pa/s were observed for UltraEZ, ReliefACP, DayWhite, and PreviDent, respectively. CONCLUSION: Potassium nitrate included in different formulations can penetrate the enamel and dentin within 30 minutes. The level of potassium nitrate penetration is influenced by concentration and may also be partly affected by the viscosity of the material as well as other constituents of proprietary preparations. PMID- 26151564 TI - Cy5.5 conjugated MnO nanoparticles for magnetic resonance/near-infrared fluorescence dual-modal imaging of brain gliomas. AB - The fusion of molecular and anatomical modalities facilitates more reliable and accurate detection of tumors. Herein, we prepared the PEG-Cy5.5 conjugated MnO nanoparticles (MnO-PEG-Cy5.5 NPs) with magnetic resonance (MR) and near-infrared fluorescence (NIRF) imaging modalities. The applicability of MnO-PEG-Cy5.5 NPs as a dual-modal (MR/NIRF) imaging nanoprobe for the detection of brain gliomas was investigated. In vivo MR contrast enhancement of the MnO-PEG-Cy5.5 nanoprobe in the tumor region was demonstrated. Meanwhile, whole-body NIRF imaging of glioma bearing nude mouse exhibited distinct tumor localization upon injection of MnO PEG-Cy5.5 NPs. Moreover, ex vivo CLSM imaging of the brain slice hosting glioma indicated the preferential accumulation of MnO-PEG-Cy5.5 NPs in the glioma region. Our results therefore demonstrated the potential of MnO-PEG-Cy5.5 NPs as a dual-modal (MR/NIRF) imaging nanoprobe in improving the diagnostic efficacy by simultaneously providing anatomical information from deep inside the body and more sensitive information at the cellular level. PMID- 26151565 TI - Formation and properties of nanostructured colloidal manganese oxide particles obtained through the thermally controlled transformation of manganese carbonate precursor phase. AB - Structurally and morphologically different colloidal manganese oxide solids, including manganosite (MnO), bixbyite (Mn2O3) and hausmannite (Mn(2+)[Mn(3+)]2O4), were obtained through the initial biomimetically induced precipitation of a uniform, nanostructured and micron-sized rhodochrosite (MnCO3) precursor phase and their subsequent thermally controlled transformation into oxide structures in air and Ar/H2 atmospheres. The structures and morphology of the obtained precipitates were investigated using X-ray diffraction (XRD) and field-emission scanning electron microscopy (FESEM). Their surface properties were investigated by electrophoretic mobilities (EPM) and specific surface area (SSA) measurements. The results showed that the structurally diverse, micron sized, spherical manganese oxide particles exhibit unusual and fascinating nanostructured surface morphologies. These were developed through the coalescence of an initially formed, nanosized, crystalline, manganese carbonate precursor phase which, during the heating, transformed into coarser, irregular, elongated, micron-sized, manganese oxide solids. It was also shown that structural transformations and morphological tailoring were followed by significant changes in the physico-chemical properties of the obtained solids. Their SSA values were drastically reduced as a result of the progressive coalescence at the particle surfaces occurring at higher temperatures. The isoelectric points (IEPs) of the obtained manganese oxides were diverse. This is the consequence of their range of crystal-chemical properties that governed the complex physico-chemical processes at the interface of the manganese oxide solid and the aqueous solution. The results of this study may lead to a conceptually new method for the synthesis of high-performance, nanostructured, manganese oxide solids with desirable structural, morphological and surface properties. PMID- 26151566 TI - Surface plasmon resonance in surfactant coated copper sulfide nanoparticles: Role of the structure of the capping agent. AB - HYPOTHESIS: The optical properties of as-synthesized CuS nanoparticles are affected by shape, size and morphology and exhibit increased optical absorbance in the infrared range due to localized surface plasmon resonance (LSPR), which is also affected by these parameters. An additional parameter which affects the LSPR related absorbance is crystallinity of the surfactant coating. EXPERIMENTS: CuS nanoparticles with varying morphologies were synthesized using a single source, single surfactant/solvent route. Thereafter, the particles were heat treated at temperatures varying from 130 degrees C to 230 degrees C with and without protective environment. Prior to and following the treatments, the particles were characterized using various techniques. Additionally, temperature resolved structural study and thermal analysis of the surfactant coating were performed. FINDINGS: We confirm that the previously reported effects of particle dimensions and chemical composition on LSPR apply for the synthesized particles. Moreover, we report an additional, previously unreported effect, connecting the crystal structure of the nanoparticle surfactant coating to LSPR. This in turn allows control over LSPR peak position by varying the degree of crystallinity of the capping surfactant layer. Thermal study of the surfactant coating showed gradual structural transition and high dependence of phase transformation on atmospheric environment during treatment. PMID- 26151567 TI - Alginate-polyester comacromer based hydrogels as physiochemically and biologically favorable entities for cardiac tissue engineering. AB - The physiochemical and biological responses of tissue engineering hydrogels are crucial in determining their desired performance. A hybrid comacromer was synthesized by copolymerizing alginate and poly(mannitol fumarate-co-sebacate) (pFMSA). Three bimodal hydrogels pFMSA-AA, pFMSA-MA and pFMSA-NMBA were synthesized by crosslinking with Ca(2+) and vinyl monomers acrylic acid (AA), methacrylic acid (MA) and N,N'-methylene bisacrylamide (NMBA), respectively. Though all the hydrogels were cytocompatible and exhibited a normal cell cycle profile, pFMSA-AA exhibited superior physiochemical properties viz non-freezable water content (58.34%) and water absorption per unit mass (0.97 g water/g gel) and pore length (19.92+/-3.91 MUm) in comparing with other two hydrogels. The increased non-freezable water content and water absorption of pFMSA-AA hydrogels greatly influenced its biological performance, which was evident from long-term viability assay and cell cycle proliferation. The physiochemical and biological favorability of pFMSA-AA hydrogels signifies its suitability for cardiac tissue engineering. PMID- 26151568 TI - Carbon bead-supported nitrogen-enriched and Cu-doped carbon nanofibers for the abatement of NO emissions by reduction. AB - Carbon nanofibers (CNFs) were grown over highly porous (~1750 m(2)/g-surface area) carbon beads (~0.8 mm), using catalytic chemical vapor deposition (CVD). The carbon beads were produced by the pre-oxidation, carbonization and activation of the phenolic beads that were synthesized using the suspension polymerization. The beads were doped in situ with copper (Cu) during the polymerization reaction. The carbon beads decorated with the CNFs were treated with pyridine to increase the nitrogen (N) contents of the material. The N-enriched CNFs and Cu nanoparticles (NPs)-doped carbon beads (N-Cu-CNF/CBs) were used for the removal of nitric oxide (NO) by reduction. In its dual role, Cu catalyzed the growth of the CNFs during CVD, and also, the reduction reaction. Approximately 86% of NO conversion was achieved for 400 ppm-NO concentration over 1 g of the prepared catalyst at 500 degrees C. The high catalytic activity was attributed to the combined roles of the Cu NPs, reactive CNFs and N-containing surface functional groups in the material. The prepared carbon bead-supported CNFs in this study are for the first time effectively used as the catalyst for the NO reduction without requiring ammonia or urea. PMID- 26151569 TI - Treatment and Prevention of Depression. AB - Depression is one of the most common and debilitating psychiatric disorders and is a leading cause of suicide. Most people who become depressed will have multiple episodes, and some depressions are chronic. Persons with bipolar disorder will also have manic or hypomanic episodes. Given the recurrent nature of the disorder, it is important not just to treat the acute episode, but also to protect against its return and the onset of subsequent episodes. Several types of interventions have been shown to be efficacious in treating depression. The antidepressant medications are relatively safe and work for many patients, but there is no evidence that they reduce risk of recurrence once their use is terminated. The different medication classes are roughly comparable in efficacy, although some are easier to tolerate than are others. About half of all patients will respond to a given medication, and many of those who do not will respond to some other agent or to a combination of medications. Electro-convulsive therapy is particularly effective for the most severe and resistant depressions, but raises concerns about possible deleterious effects on memory and cognition. It is rarely used until a number of different medications have been tried. Although it is still unclear whether traditional psychodynamic approaches are effective in treating depression, interpersonal psychotherapy (IPT) has fared well in controlled comparisons with medications and other types of psychotherapies. It also appears to have a delayed effect that improves the quality of social relationships and interpersonal skills. It has been shown to reduce acute distress and to prevent relapse and recurrence so long as it is continued or maintained. Treatment combining IPT with medication retains the quick results of pharmacotherapy and the greater interpersonal breadth of IPT, as well as boosting response in patients who are otherwise more difficult to treat. The main problem is that IPT has only recently entered clinical practice and is not widely available to those in need. Cognitive behavior therapy (CBT) also appears to be efficacious in treating depression, and recent studies suggest that it can work for even severe depressions in the hands of experienced therapists. Not only can CBT relieve acute distress, but it also appears to reduce risk for the return of symptoms as long as it is continued or maintained. Moreover, it appears to have an enduring effect that reduces risk for relapse or recurrence long after treatment is over. Combined treatment with medication and CBT appears to be as efficacious as treatment with medication alone and to retain the enduring effects of CBT. There also are indications that the same strategies used to reduce risk in psychiatric patients following successful treatment can be used to prevent the initial onset of depression in persons at risk. More purely behavioral interventions have been studied less than the cognitive therapies, but have performed well in recent trials and exhibit many of the benefits of cognitive therapy. Mood stabilizers like lithium or the anticonvulsants form the core treatment for bipolar disorder, but there is a growing recognition that the outcomes produced by modern pharmacology are not sufficient. Both IPT and CBT show promise as adjuncts to medication with such patients. The same is true for family-focused therapy, which is designed to reduce interpersonal conflict in the family. Clearly, more needs to be done with respect to treatment of the bipolar disorders. Good medical management of depression can be hard to find, and the empirically supported psychotherapies are still not widely practiced. As a consequence, many patients do not have access to adequate treatment. Moreover, not everyone responds to the existing interventions, and not enough is known about what to do for people who are not helped by treatment. Although great strides have been made over the past few decades, much remains to be done with respect to the treatment of depression and the bipolar disorders. PMID- 26151570 TI - Plasma-enhanced microwave solid-state synthesis of cadmium sulfide: reaction mechanism and optical properties. AB - CdS synthesis by plasma-enhanced microwave physical vapor transport (PMPVT) has been developed in this work. The photoluminescence (PL), absorbance, Raman spectra and the mechanism of CdS crystal growth have been investigated. Furthermore, plasma-enhanced microwave chemical vapour transport (PMCVT) synthesis of CdS with additional chemical transport agents has been explored. In addition, other II-VI chalcogenides were also synthesized by PMPVT. PMID- 26151571 TI - Glutathione S-transferase pi expression regulates the Nrf2-dependent response to hormetic diselenides. AB - Glutathione S-transferase pi (GSTP), a phase II gene downstream of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant-responsive element (ARE)/electrophile response element (EpRE) transcription pathway, plays a key role in both the signaling and detoxification response to Se-organic compounds with thiol peroxidase activity. We here investigated the role of GSTP on the Nrf2 activation response of cells challenged with a new class of diselenides derived from the basic structure of diphenyl diselenide [(PhSe)2]. These diselenides, and particularly 2,2'-diselenyl dibenzoic acid (DSBA), behave as mild thiol peroxidases leading to a moderate generation of H2O2 and NOx, and signaling of stress-activated and survival-promoting MAPKs, which ultimately control the mitochondrial pathway of apoptosis. Used in murine embryonic fibroblasts (MEFs) and HepG2 human hepatocarcinoma cells to produce submaximal conditions of stress, the diselenide compounds stimulated Nrf2 nuclear translocation and then the transcription of the same Nrf2 gene as well as of GSTP and other phase II genes. This resulted in a higher degree of protection against H2O2 cytotoxicity (hormetic effect). Diselenide toxicity increased in GSTP knockout MEFs by a higher generation of NOx and stress activated protein kinase (SAPK)/JNK activation. A lowered hormetic potential of these cells was observed in association with an abnormal expression and nuclear translocation of Nrf2 protein. Immunoprecipitation and affinity purification experiments revealed the existence of an Nrf2/GSTP complex in MEFs and HepG2 cells. Covalent oligomers of GSTP subunits were observed in DSBA-treated HepG2 cells. In conclusion, GSTP gene expression influences the Nrf2-dependent response to hormetic diselenides. Mechanistic interpretation for this GSTP-dependent effect may include a direct and redox-sensitive interaction of GSTP with Nrf2 protein. PMID- 26151572 TI - Kindlin-2 controls TGF-beta signalling and Sox9 expression to regulate chondrogenesis. AB - The signals that control skeletogenesis are incompletely understood. Here we show that deleting Kindlin-2 in Prx1-expressing mesenchymal progenitors in mice causes neonatal lethality, chondrodysplasia and loss of the skull vault. Kindlin-2 ablation reduces chondrocyte density by decreasing cell proliferation and increasing apoptosis, and disrupts column formation, thus impairing the formation of the primary ossification center and causing severe limb shortening. Remarkably, Kindlin-2 localizes to not only focal adhesions, but also to the nuclei of chondrocytes. Loss of Kindlin-2 reduces, while the overexpression of Kindlin-2 increases, Sox9 expression. Furthermore, the overexpression of Sox9 restores the defects in chondrogenic differentiation induced by Kindlin-2 deletion in vitro. In addition, Kindlin-2 ablation inhibits TGF-beta1-induced Smad2 phosphorylation and chondrocyte differentiation. Finally, deleting Kindlin 2 in chondrocytes directly impairs chondrocyte functions, resulting in progressive dwarfism and kyphosis in mice. These studies uncover a previously unrecognized function for Kindlin-2 and a mechanism for regulation of the chondrocyte differentiation programme and chondrogenesis. PMID- 26151574 TI - Heptacoordinate Heteroleptic Salan (ONNO) and Thiosalan (OSSO) Titanium(IV) Complexes: Investigation of Stability and Cytotoxicity. AB - Seven heptacoordinate titanium(IV) complexes were synthesized based on the concept of hetero-bis-chelate stabilization of salan (ONNO) and thiosalan (OSSO) titanium(IV)alkoxides with 2,6-pyridinedicarboxylic acid (dipic) and derivatives thereof. The resulting compounds were investigated in a solid by X-ray diffraction and in solution by NMR spectroscopy. A thiosalan (OSSO) titanium(IV) complex could be isolated and its conformational stabilization by dipic was shown by (1)H NMR spectroscopy to lead to nonfluxional behavior even at room temperature. The stability of selected complexes was assessed at pH 1.9, 6.8, and 12.1 by an UV-vis monitored hydrolysis study with >5 Mio. equivalents of water. Even at pH 12.1 [L(1)Ti(dipic)(1)] showed t1/2 of more than 2 days. The cytotoxicity of all compounds was investigated in two human carcinoma cell lines. IC50-values in the range of cisplatin were achieved by all tested compounds except for [L(4)Ti(dipic)(1)], which was proven to be nontoxic. The functionalization of dipic was thus well tolerated and did neither interfere with the stability nor the cytotoxicity of the heteroleptic complexes. PMID- 26151573 TI - Knockdown of SOX18 inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells. AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Recent studies have demonstrated that SOX18 is highly expressed in various types of cancer. In the present study, we found that SOX18 mRNA was overexpressed in HCC compared with non-tumorous tissues. We aimed to explore the effects of SOX18 siRNA on the proliferation, invasion and migration of two HCC cell lines, MHCC97H and HepG2, which overexpress SOX18. We found that SOX18 siRNA significantly inhibited the proliferation and induced cell cycle arrest at the G0/G1 phase. Results of the Transwell assay showed that the migration and invasion of the HCC cells were markedly impaired in the SOX18-knockdown cells. Gene set enrichment analysis (GSEA) showed that KEGG focal adhesion and chemokine signaling pathways were correlated with SOX18 expression. Furthermore, the mRNA and protein levels of RhoA, PDGFB, IGF1R, CCL2, CCL3 and CCL5 were decreased in the SOX18-knockdown cells. Importantly, we demonstrated that upregulation of SOX18 was associated with a poor outcome in HCC patients. These results indicate that SOX18 may serve as a prognostic factor and a promising therapeutic strategy for HCC. PMID- 26151576 TI - Postoperative lumbar epidural abscess: conventional and advanced magnetic resonance imaging findings. PMID- 26151577 TI - Huge paravertebral masses in Proteus syndrome. PMID- 26151575 TI - The type II histidine triad protein HtpsC is a novel adhesion with the involvement of Streptococcus suis virulence. AB - Streptococcal histidine triad proteins HTPs are widely distributed within the Streptococcus genus. Based on the phylogenetic relationship and domain composition, HTPs are classified into type I and type II subfamilies. Previous studies revealed that several pathogenic streptococci contain more than one htp gene. We found that the highly virulent strain of Streptococcus suis 2 (S. suis 2), 05ZYH33 encodes 3 HTPs, designated HtpsA (previously described as HtpS), HtpsB, and HtpsC. Among them, HtpsC is the only member that contains leucine-rich repeat (LRR) domains at the C-terminal. In this study, we demonstrated that the recombinant HtpsC could bind to 2 different components of human ECM complex laminin and fibronectin in vitro, suggesting that it is a novel adhesin of S. suis 2. Having constructed an htpsC mutant, we evaluated its role in the pathogenesis of the highly virulent S. suis 2 strain 05ZYH33. Our data showed that inactivation of htpsC significantly affected adherence of S. suis 2 to Hep-2 cells and shortened the survival of the bacteria in whole blood. Furthermore, deletion of htpsC significantly attenuated the virulence of S. suis 2 in mice. These results demonstrated that htpsC was involved in the pathogenesis of the highly virulent S. suis 2 strain 05ZYH33. In line with the observation, immunization with HtpsC significantly prolonged mice's survival after S. suis 05ZYH33 challenge, indicating its potential use in the vaccine development against S. suis. PMID- 26151578 TI - Evaluation of recurrent vertebral hydatid cyst with computed tomography myelography in a case with spinal instrumentation. PMID- 26151579 TI - New methods shed light on age of onset as a risk factor for nicotine dependence. AB - INTRODUCTION: Early onset of substance use is a risk factor for later drug use, abuse, and dependence. This study examines how the rate of nicotine dependence differs as a function of age of onset of regular smoking in continuous time, in order to identify critical age periods that are most predictive of later dependence for males and females. METHODS: Time-varying effect modeling (TVEM) can reveal specific ages of onset that confer greatest risk for adult nicotine dependence. The rate of dependence in adulthood is modeled as a flexible function of age of onset using a subset of adults (N = 15,748) from the National Epidemiologic Survey on Alcohol and Related Conditions who ever smoked regularly. RESULTS: The peak risk of adult nicotine dependence coincides with onset of regular use at approximately 10 years old, with an elevated risk persisting to 20 years. The risk of dependence is significantly higher for females compared to males for onset of regular use between ages 9 and 18. CONCLUSIONS: Results suggest that the risk of adult nicotine dependence is highest when onset of regular smoking occurs at around 10 years, though the associated risk is high for ages of onset into young adulthood. Early onset of regular use is a relatively stronger risk factor for adolescent females than males. Smoking prevention programs should focus on late childhood through early adolescence, particularly among females. TVEM provides a more nuanced understanding of the risk associated with different ages of onset of health risk behaviors. PMID- 26151580 TI - Insomnia in alcohol dependent subjects is associated with greater psychosocial problem severity. AB - INTRODUCTION: Although psychosocial problems are commonly associated with both alcohol misuse and insomnia, very little is known about the combined effects of insomnia and current alcohol dependence on the severity of psychosocial problems. The present study evaluates whether the co-occurrence of insomnia and alcohol dependence is associated with greater psychosocial problem severity. METHODS: Alcohol dependent individuals (N = 123) were evaluated prior to participation in a placebo-controlled medication trial. The Short Index of Problems (SIP), Addiction Severity Index (ASI), Insomnia Severity Index (ISI), and Time Line Follow Back (TLFB), were used to assess psychosocial, employment, and legal problems; insomnia symptoms; and alcohol consumption, respectively. Bivariate and multivariate analyses were used to evaluate the relations between insomnia and psychosocial problems. RESULTS: Subjects' mean age was 44 years (SD = 10.3), 83% were male, and their SIP sub-scale scores approximated the median for normative data. A quarter of subjects reported no insomnia; 29% reported mild insomnia; and 45% reported moderate-severe insomnia. The insomnia groups did not differ on alcohol consumption measures. The ISI total score was associated with the SIP total scale score (beta = 0.23, p = 0.008). Subjects with moderate-severe insomnia had significantly higher scores on the SIP total score, and on the social and impulse control sub-scales, and more ASI employment problems and conflicts with their spouses than others on the ASI. CONCLUSION: In treatment seeking alcohol dependent subjects, insomnia may increase alcohol-related adverse psychosocial consequences. Longitudinal studies are needed to clarify the relations between insomnia and psychosocial problems in these subjects. PMID- 26151581 TI - E-cigarette use among Texas youth: Results from the 2014 Texas Youth Tobacco Survey. AB - INTRODUCTION: Several characteristics of electronic cigarettes (e-cigarettes), such as candy flavorings, are worrisome for attracting youth. The current cross sectional study uses data on e-cigarette use from the 2014 Texas Youth Tobacco Survey (TYTS), a representative statewide sample of Texas middle school and high school students. This study's aims are to determine the prevalence of e-cigarette use, including rates of concurrent use with other tobacco products among Texas youth and to describe the demographic and tobacco use differences between e cigarette users and non-users. METHODS: Participants were 13,602 6th through 12th grade students in Texas. Descriptive statistics were generated to determine the prevalence of current and lifetime e-cigarette use and to determine the prevalence of demographic characteristics across e-cigarette usage groups. Logistic regression analyses were conducted to examine differences in demographic characteristics, cigarette use in the home, and tobacco use behaviors for e cigarette users versus non-users. RESULTS: Almost one quarter of all middle and high school students reported lifetime e-cigarette use and 14.0% were past 30-day users of these products. Current e-cigarette users were more likely to be high school students, white and male than non-current users. Both current and lifetime e-cigarette users were also more likely than their peers to use other tobacco products, although 24.2% of current e-cigarette users had never smoked conventional cigarettes, and 7.3% had never used any other type of tobacco product besides an e-cigarette. CONCLUSIONS: Findings highlight the urgency to regulate e-cigarettes as well as to include these products in tobacco prevention programs. PMID- 26151582 TI - Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users. AB - INTRODUCTION: Individuals report using cannabis for the promotion of sleep, and the effects of cannabis on sleep may vary by cannabis species. Little research has documented preferences for particular cannabis types or cannabinoid concentrations as a function of use for sleep disturbances. METHODS: 163 adults purchasing medical cannabis for a physical or mental health condition at a cannabis dispensary were recruited. They provided self-report of (a) whether cannabis use was intended to help with sleep problems (e.g. insomnia, nightmares), (b) sleep quality (PSQI), (c) cannabis use (including preferred type), and (d) symptoms of DSM-5 cannabis dependence. RESULTS: 81 participants reported using cannabis for the management of insomnia and 14 participants reported using cannabis to reduce nightmares. Individuals using cannabis to manage nightmares preferred sativa to indica strains (Fisher's exact test (2) = 6.83, p < 0.05), and sativa users were less likely to endorse DSM-5 cannabis dependence compared with those who preferred indica strains (chi(2)(2) = 4.09, p < 0.05). Individuals with current insomnia (t(9) = 3.30, p < 0.01) and greater sleep latency (F(3,6) = 46.7, p < 0.001) were more likely to report using strains of cannabis with significantly higher concentrations of CBD. Individuals who reported at least weekly use of hypnotic medications used cannabis with lower THC concentrations compared to those who used sleep medications less frequently than weekly (t(17) = 2.40, p < 0.05). CONCLUSIONS: Associations between sleep characteristics and the type of cannabis used were observed in this convenience sample of individuals using cannabis for the management of sleep disturbances. Controlled prospective studies are needed to better characterize the impact that specific components of cannabis have on sleep. PMID- 26151583 TI - Evaluation of methamphetamine-associated socioeconomic status and addictive behaviors, and their impact on oral health. AB - BACKGROUND: Chronic methamphetamine abuse can lead to multiple health hazards. In particular, the substance is associated with devastating effects on oral health including symptoms such as rampant caries, gingiva inflammation, and xerostomia, whereby the term "Meth Mouth" occurs in the current literature. However, "Meth Mouth" pathology is primarily described on the basis of individual cases or has been evaluated without consideration of the mass of potential influencing factors. Therefore, we have conducted a systematic study to investigate the effects of accompanying factors and circumstances on oral health in cases of chronic methamphetamine abuse. METHODS: In cooperation with two centers for addiction medicine, we assessed the data of 100 chronic methamphetamine users and 100 matched-pair controls between March 2012 and November 2013. We investigated their socioeconomic status, details of methamphetamine consumption behavior, collateral consumption of sugar beverages, nicotine alcohol, and other addictive substances including cannabis, opioids, other stimulants, and hallucinogens, and dental care. RESULTS: We found considerably greater unstable social circumstances, a high collateral consumption of substances with pathogenic potential for the stomatognathic system, and significantly poorer dental care in the methamphetamine-user group. CONCLUSIONS: Various factors have to be considered with regard to methamphetamine use and its influence on oral health. These factors can trigger potential damage by the drug methamphetamine possibly leading to the symptoms of "Meth Mouth", and should be considered in prevention and therapy strategies. PMID- 26151584 TI - An Examination of the Indirect Effect of Anxiety Sensitivity in terms of Asthma and Smoking Cessation Processes. AB - INTRODUCTION: Despite the increased rates of smoking and poor cessation outcomes among individuals with asthma relative to those without, little scholarly attention has examined mechanisms linking asthma to smoking cessation processes. The current study sought to examine the indirect effect of anxiety sensitivity in terms of asthma and smoking cessation processes (i.e., duration of longest quit attempt, motivation to quit smoking, smoking dependence motives). METHODS: Participants were 90 regular daily smokers: 43 with asthma (51.2% male, M(age) = 38.0 years, SD = 12.5) and 47 without asthma (46.8% male, M(age) = 35.4 years, SD = 11.2) who were participating in a larger smoking cessation study. Data from the baseline (pre-quit attempt) assessment session were used. RESULTS: After accounting for the effects of gender, race, daily smoking rate, and negative affectivity, asthma status was indirectly related to motives for smoking related to nicotine dependence and motivation to quit smoking through anxiety sensitivity. There was no significant indirect effect for duration of longest quit attempt. CONCLUSIONS: These findings suggest that smokers with asthma may be particularly fearful of physiological arousal, which in turn, may account for greater motivation to quit smoking, but also stronger dependence motives for smoking. PMID- 26151585 TI - Patterns of use of other drugs among those with alcohol dependence: Associations with drinking behavior and psychopathology. AB - INTRODUCTION: Alcohol dependence (AD) presents with substantial clinical heterogeneity, including concurrent use of non-alcohol drugs. Here, we examine specific patterns of concurrent non-alcohol substance use during the previous year among a nationally representative sample of adults with DSM-IV AD, and estimate their population prevalence in the U.S. We then evaluate alcohol use behavior and comorbid psychopathology among respondents with AD according to their patterns of concurrent non-alcohol substance use. METHODS: These analyses utilized data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Latent class analyses classified respondents with AD into four clinically meaningful patterns of concurrent substance use: (1) use of alcohol only; (2) use of alcohol and tobacco only; (3) use of alcohol, tobacco and cannabis; and (4) use of alcohol, tobacco, cannabis, cocaine, and other illicit drug(s). RESULTS: Among AD respondents, the most prevalent pattern was the use of alcohol and tobacco only (weighted percentage, 32.4%), followed by the use of alcohol only (weighted percentage, 27.5%). AD respondents who used alcohol, tobacco, cannabis, cocaine, and other illicit drug(s) (weighted percentage, 25.3%) manifested the most severe pattern of alcohol consumption, and had significant overrepresentations of major depression, panic, and other anxiety disorders as well as paranoid, schizotypal, borderline, antisocial, and histrionic personality disorders compared with those who used alcohol alone. CONCLUSIONS: Specific patterns of concurrent substance use convey important information regarding the clinical presentation and prognosis for AD. In particular, concurrent use of illicit drugs over the past year by AD individuals was associated with greater severity and comorbid psychopathology. These data suggest the need for pragmatic trials of AD interventions that take into account patterns of substance use behavior in addition to an AD diagnosis. PMID- 26151586 TI - Environmental exposures to metals in Native communities and implications for child development: basis for the Navajo birth cohort study. AB - Two disparate statistics often cited for the Western United States raise concern about risks for developmental disabilities in Native American children. First, 13 of the states with the highest percentage of Native American population are located in the Western United States (U.S. Census Bureau, 2012 ). Second, more than 161,000 abandoned hard-rock mines are located in 12 Western states (General Accounting Office, 2014 ). Moreover, numerous studies have linked low-level metals exposure with birth defects and developmental delays. Concern has emerged among tribal populations that metals exposure from abandoned mines might threaten development of future generations. PMID- 26151587 TI - Generation of late-born neurons in the ventral spinal cord requires the coordination of retinoic acid and Notch signaling. AB - Neural progenitor cells generate various types of neurons and glia in a tightly regulated manner. During primary neurogenesis, retinoic acid (RA) acts earlier than Notch signaling and regulates differentiation and proliferation by upregulating proneural and neurogenic genes in the neural plate. However, the relationship between Notch signaling and the retinoid pathway during late neurogenesis remains unclear. We investigated the role of Mindbomb (Mib)-mediated Notch signaling in the differentiation of neural progenitors during late neurogenesis by overexpressing Mib and administering RA to Tg[hsp70-Mib:EGFP]. The majority of cells in the p3 domain differentiated into GABAergic Kolmer Agduhr (KA) cells in Tg[hsp70-mib:EGFP] embryos heat-shocked during late neurogenesis, whereas these phenotypes were suppressed by exogenous RA. Our observations suggest that Mib-mediated Notch signaling plays a critical role in the temporal differentiation of neural progenitors, and that the generation of late-born KA" cells is regulated by the interplay between Mib and RA. PMID- 26151588 TI - Evolutionary dynamics of collective action in spatially structured populations. AB - Many models proposed to study the evolution of collective action rely on a formalism that represents social interactions as n-player games between individuals adopting discrete actions such as cooperate and defect. Despite the importance of spatial structure in biological collective action, the analysis of n-player games games in spatially structured populations has so far proved elusive. We address this problem by considering mixed strategies and by integrating discrete-action n-player games into the direct fitness approach of social evolution theory. This allows to conveniently identify convergence stable strategies and to capture the effect of population structure by a single structure coefficient, namely, the pairwise (scaled) relatedness among interacting individuals. As an application, we use our mathematical framework to investigate collective action problems associated with the provision of three different kinds of collective goods, paradigmatic of a vast array of helping traits in nature: "public goods" (both providers and shirkers can use the good, e.g., alarm calls), "club goods" (only providers can use the good, e.g., participation in collective hunting), and "charity goods" (only shirkers can use the good, e.g., altruistic sacrifice). We show that relatedness promotes the evolution of collective action in different ways depending on the kind of collective good and its economies of scale. Our findings highlight the importance of explicitly accounting for relatedness, the kind of collective good, and the economies of scale in theoretical and empirical studies of the evolution of collective action. PMID- 26151589 TI - An improved model for whole genome phylogenetic analysis by Fourier transform. AB - DNA sequence similarity comparison is one of the major steps in computational phylogenetic studies. The sequence comparison of closely related DNA sequences and genomes is usually performed by multiple sequence alignments (MSA). While the MSA method is accurate for some types of sequences, it may produce incorrect results when DNA sequences undergone rearrangements as in many bacterial and viral genomes. It is also limited by its computational complexity for comparing large volumes of data. Previously, we proposed an alignment-free method that exploits the full information contents of DNA sequences by Discrete Fourier Transform (DFT), but still with some limitations. Here, we present a significantly improved method for the similarity comparison of DNA sequences by DFT. In this method, we map DNA sequences into 2-dimensional (2D) numerical sequences and then apply DFT to transform the 2D numerical sequences into frequency domain. In the 2D mapping, the nucleotide composition of a DNA sequence is a determinant factor and the 2D mapping reduces the nucleotide composition bias in distance measure, and thus improving the similarity measure of DNA sequences. To compare the DFT power spectra of DNA sequences with different lengths, we propose an improved even scaling algorithm to extend shorter DFT power spectra to the longest length of the underlying sequences. After the DFT power spectra are evenly scaled, the spectra are in the same dimensionality of the Fourier frequency space, then the Euclidean distances of full Fourier power spectra of the DNA sequences are used as the dissimilarity metrics. The improved DFT method, with increased computational performance by 2D numerical representation, can be applicable to any DNA sequences of different length ranges. We assess the accuracy of the improved DFT similarity measure in hierarchical clustering of different DNA sequences including simulated and real datasets. The method yields accurate and reliable phylogenetic trees and demonstrates that the improved DFT dissimilarity measure is an efficient and effective similarity measure of DNA sequences. Due to its high efficiency and accuracy, the proposed DFT similarity measure is successfully applied on phylogenetic analysis for individual genes and large whole bacterial genomes. PMID- 26151590 TI - Rapid Screening of Multiclass Syrup Adulterants in Honey by Ultrahigh-Performance Liquid Chromatography/Quadrupole Time of Flight Mass Spectrometry. AB - Honey adulteration with sugar syrups is a widespread problem. Several types of syrups have been used in honey adulteration, and there is no available method that can simultaneously detect all of these adulterants. In this study, we generated a small-scale database containing the specific chromatographic and mass spectrometry information on sugar syrup markers and developed a simple, rapid, and effective ultrahigh-performance liquid chromatography/quadrupole time-of flight mass spectrometry (UHPLC/Q-TOF-MS) method for the detection of adulterated honey. Corn syrup, high-fructose corn syrup, inverted syrup, and rice syrup were used as honey adulterants; polysaccharides, difructose anhydrides, and 2 acetylfuran-3-glucopyranoside were used as detection markers. The presence of 10% sugar syrup in honey could be easily detected in <30 min using the developed method. The results revealed that UHPLC/Q-TOF-MS was simple and rapid. PMID- 26151591 TI - A cross-sectional imaging study to identify organs at risk of thermal injury during renal artery sympathetic denervation. AB - BACKGROUND: The technology used to perform catheter-based renal artery sympathetic denervation has evolved: catheters can now access arteries as small as 3mm in diameter and create ablation zones of up to 10mm in depth. Recent evidence suggests that the procedure may be more effective if a more thorough ablation strategy is employed. Limited data are available regarding inadvertent soft tissue thermal injury during such procedures. We used computed tomography (CT) to identify structures lying within the expected thermal ablation field or the 'at risk zone' (ARZ). METHODS: 63 consecutive CT aortograms were reviewed, yielding 100 renal arteries anatomically eligible for treatment. Structures lying within a predefined ARZ (within 10mm of the renal artery wall) were recorded. RESULTS: The 63 subjects had a mean age of 74.6years, 48% were males and 88% had hypertension. The inferior vena cava and renal veins were in the ARZ in all cases. Psoas muscles and small bowel were within the ARZ in at least a fifth of the kidneys. Other structures found in the ARZ included the liver, pancreas, adrenal glands and diaphragm. CONCLUSIONS: This study describes the variable anatomical relationship between renal arteries and important abdominal structures that may be exposed to thermal energy during modern denervation procedures. The consequence of delivering such thermal energy to these structures is unknown but clinicians should be alert to the presenting symptoms if these structures are damaged. CT may have a pre-procedure role in assessing this risk. PMID- 26151592 TI - Letter to editor for "Long-term risk of acute coronary syndrome in hepatitis C virus infected patients without antiviral treatment: A cohort study from endemic area". PMID- 26151593 TI - Simple stress echocardiography unmasks early pulmonary vascular disease in adult congenital heart disease. PMID- 26151594 TI - Takotsubo cardiomyopathy precipitated by anticipation of elective coronary intervention. PMID- 26151595 TI - Prognostic value of low QRS voltage in patients with acute coronary syndrome. PMID- 26151596 TI - A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window. AB - BACKGROUND: A therapeutic window in antiplatelet treatment has been associated with concurrent lowering of bleeding and ischemic risks. Prasugrel and ticagrelor provide potent platelet inhibition, but may increase bleeding. No study has evaluated a personalized therapy with selective use of novel P2Y12 inhibitory agents compared to empiric ticagrelor use. The objective of this study was to compare a personalized anti-platelet therapy strategy to empiric ticagrelor in achieving a therapeutic window. METHODS: Using the CAPITAL registry, we performed a retrospective analysis to evaluate a personalized anti-platelet therapy (PAT) strategy, using a pharmacogenetic approach, and compared it to empiric ticagrelor. In the PAT group, carriers of CYP2C19*2 received prasugrel and non carriers received clopidogrel. The primary outcome was the proportion of patients within a validated therapeutic window, after a steady state treatment (>=48h) of antiplatelet therapy, as measured by a P2Y12 reaction unit (PRU) >85 and <208. RESULTS: Of 199 patients with platelet function measurements, 150 received PAT, while 49 received ticagrelor. Significantly more patients on PAT achieved the primary outcome (50.0% vs. 4.1%, p<0.0001). This was predominantly driven by an increase in low on-treatment reactivity with ticagrelor (95.9% vs. 37.3%, p<0.0001). Multivariable analysis demonstrated PAT to be the strongest predictor of achieving PRU values within the therapeutic window (odds ratio 20.27; 95% CI: 4.33-94.82, p=0.0001). CONCLUSION: Patients treated with PAT were more likely to achieve a therapeutic window compared to a strategy of ticagrelor. Future prospective evaluation of novel PAT strategies will be required to prove clinical utility. PMID- 26151597 TI - Looking beyond lumen: Optical coherence tomography. PMID- 26151598 TI - Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3. AB - Pirt is a transmembrane protein predominantly expressed in peripheral neurons. However, the physiological and pathological roles of Pirt in hollow viscus are largely unknown. Here we show that Pirt deficiency in mice causes bladder overactivity. The density of alpha,beta-meATP-induced currents is significantly reinforced in Pirt-deficient dorsal root ganglion (DRG) neurons. Pirt and P2X3 receptor co-localize in bladder nerve fibres and heterologous Pirt expression significantly reduces P2X3-mediated currents. Pirt interacts with P2X3 through the N-terminal 14 amino-acid residues. TAT-conjugated Pirt(N14) peptide (Pirt(N14)) is sufficient to inhibit P2X3 activation in bladder DRG neurons and to alleviate bladder overactivity in Pirt(-/-) mice. Pirt expression is decreased in the bladder of cyclophosphamide (CYP)-treated mice, a commonly used model of bladder overactivity. Importantly, Pirt(N14) administration reduces the frequency of bladder voiding and restores the voided volume of CYP-treated mice. Therefore, our results demonstrate that Pirt is an endogenous regulator of P2X3 in bladder function. PMID- 26151600 TI - Simultaneous Activation of Nrf2 and Elevation of Dietary and Endogenous Antioxidant Chemicals for Cancer Prevention in Humans. AB - Despite extensive studies in cancer prevention, the incidence of cancer is increasing. We review studies that have identified several biochemical and genetic defects as well as potential carcinogens in the diet, environmental factors, and lifestyle-related habits. Two of the biochemical abnormalities increased oxidative stress and chronic inflammation, and chronic exposure to carcinogens and mutagens play a significant role in the initiation of multistage carcinogenesis. Therefore, attenuation of these biochemical defects may be useful in reducing the incidence of cancer. Activation of the transcriptional factor called nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which enhances the levels of antioxidant enzymes and phase-2-detoxifying enzymes by complex mechanisms, may be one of the ways to reduce oxidative stress and chronic inflammation. Antioxidant enzymes destroy free radicals by catalysis, whereas phase-2-detoxifying enzymes remove potential carcinogens by converting them to harmless compounds for elimination from the body. However, increasing the levels of antioxidant enzymes by activating Nrf2 may not be sufficient to decrease oxidative stress and chronic inflammation optimally, because antioxidant chemicals, which are decreased in a high oxidative environment, must also be elevated. This review discusses the regulation of activation of Nrf2 and proposes a hypothesis that an elevation of the levels of antioxidant enzymes and dietary and endogenous antioxidant chemicals simultaneously may reduce the incidence of cancer by decreasing oxidative stress and chronic inflammation. The levels of antioxidant chemicals can be increased by supplementation, but increasing the levels of antioxidant enzymes requires activation of Nrf2 by reactive oxygen species (ROS)-dependent and-independent mechanisms. Several phytochemicals and antioxidant chemicals that activate Nrf2 have been identified. This review also describes clinical studies on antioxidants in cancer prevention that have produced inconsistent results. It discusses the possible reasons for the inconsistent results and proposes criteria that should be included in the experimental designs of future clinical studies to obtain consistent results. KEY TEACHING POINTS: * Reducing oxidative stress and chronic inflammation optimally requires an elevation of the levels of antioxidant enzymes and phase-2 detoxifying enzymes as well as dietary and endogenous antioxidant chemicals. * How the levels of antioxidant enzymes and phase-2-detoxifying enzymes are regulated by a nuclear transcriptional factor Nrf2. * How the activation and transcription of Nrf2 is regulated. * Identification of antioxidants that activate Nrf2 by ROS-dependent and-independent mechanisms, those that destroy free radicals by scavenging, and those that exhibit both functions. * Possible reasons for the inconsistent results produced by the previous clinical studies on antioxidants in cancer prevention. * The criteria that should be included in the experimental designs of future clinical studies on antioxidants in cancer prevention in high-risk populations to obtain consistent results. PMID- 26151599 TI - Kicking it up a Notch for the best in show: Scalloped leads Yorkie into the haematopoietic arena. AB - Maintenance and differentiation of progenitor cells is essential for proper organ development and adaptation to environmental stress and injury. In Drosophila melanogaster, the haematopietic system serves as an ideal model for interrogating the function of signaling pathways required for progenitor maintenance and cell fate determination. Here we focus on the role of the Hippo pathway effectors Yorkie and Scalloped in mediating and facilitating Notch signaling-mediated lineage specification in the lymph gland, the primary center for haematopoiesis within the developing larva. We discuss the regulatory mechanisms which promote Notch activity during normal haematopoiesis and its modulation during immune challenge conditions. We provide additional evidence establishing the hierarchy of signaling events during crystal cell formation, highlighting the relationship between Yorkie, Scalloped and Lozenge, while expanding on the role of Yorkie in promoting hemocyte survival and the developmental regulation of Notch and its ligand, Serrate, within the lymph gland. Finally, we propose additional areas of exploration that may provide mechanistic insight into the environmental and non cell autonomous regulation of cell fate in the blood system. PMID- 26151601 TI - Conjugated Polyelectrolyte-Sensitized TiO2 Solar Cells: Effects of Chain Length and Aggregation on Efficiency. AB - Two sets of conjugated polyelectrolytes with different molecular weights (Mn) in each set were synthesized. All polymers feature the same conjugated backbone with alternating (1,4-phenylene) and (2,5-thienylene ethynylene) repeating units, but different linkages between the backbone and side chains, namely, oxy-methylene ( O-CH2-) (P1-O-n, where n = 7, 9, and 14) and methylene (-CH2-) (P2-C-n, n = 7, 12, and 18). They all bear carboxylic acid moieties as side chains, which bind strongly to titanium dioxide (TiO2) nanoparticles. The two sets of polymers were used as light-harvesting materials in dye-sensitized solar cells. Despite the difference in molecular weight, polymers within each set have very similar light absorption properties. Interestingly, under the same working conditions, the overall cell efficiency of the P1-O-n series increases with a decreasing molecular weight while the efficiency of the P2-C-n series remains constant regardless of the molecular weight. Steady state photophysical measurements and dynamic light scattering investigation prove that P1-O-n polymers aggregate in solution while P2-C-n series are in the monomeric state. In P1-O-n series, a higher-molecular weight polymer results in a larger aggregate, which reduces the amount of polymers that are adsorbed onto TiO2 films and overall cell efficiency. PMID- 26151602 TI - Three Dimensional Nano "Langmuir Trough" for Lipid Studies. AB - A three-dimensional-phospholipid monolayer with tunable molecular structure was created on the surface of oil nanodroplets from a mixture of phospholipids, oil, and water. This simple nanoemulsion preparation technique generates an in situ prepared membrane model system with controllable molecular surface properties that resembles a lipid droplet. The molecular interfacial structure of such a nanoscopic system composed of hexadecane, 1,2-dihexadecanoyl-sn-glycero-3 phosphocholine (DPPC), and water was determined using vibrational sum frequency scattering and second harmonic scattering techniques. The droplet surface structure of DPPC can be tuned from a tightly packed liquid condensed phase like monolayer to a more dilute one that resembles the liquid condensed/liquid expanded coexistence phase by varying the DPPC/oil/water ratio. The tunability of the chemical structure, the high surface-to-volume ratio, and the small sample volume make this system an ideal model membrane for biochemical research. PMID- 26151603 TI - Knocking on wood: base metal complexes as catalysts for selective oxidation of lignin models and extracts. AB - This work began as part of a biomass conversion catalysis project with UC Santa Barbara funded by the first NSF Chemical Bonding Center, CATSB. Recognizing that catalytic aerobic oxidation of diol C-C bonds could potentially be used to break down lignocellulose, we began to synthesize oxovanadium complexes and explore their fundamental reactivity. Of course there were theories regarding the oxidation mechanism, but our mechanistic studies soon revealed a number of surprises of the type that keep all chemists coming back to the bench! We realized that these reactions were also exciting in that they actually used the oxygen-on-every-carbon property of biomass-derived molecules to control the selectivity of the oxidation. When we found that these oxovanadium complexes tended to convert sugars predominantly to formic acid and carbon dioxide, we replaced one of the OH groups with an ether and entered the dark world of lignin chemistry. In this Account, we summarize results from our collaboration and from our individual labs. In particular, we show that oxidation selectivity (C-C vs C O bond cleavage) of lignin models using air and vanadium complexes depends on the ancillary ligands, the reaction solvent, and the substrate structure (i.e., phenolic vs non-phenolic). Selected vanadium complexes in the presence of added base serve as effective alcohol oxidation catalysts via a novel base-assisted dehydrogenation pathway. In contrast, copper catalysts effect direct C-C bond cleavage of these lignin models, presumably through a radical pathway. The most active vanadium catalyst exhibits unique activity for the depolymerization of organosolv lignin. After Weckhuysen's excellent 2010 review on lignin valorization, the number of catalysis studies and approaches on both lignin models and extracts has expanded rapidly. Today we are seeing new start-ups and lignin production facilities sprouting up across the globe as we all work to prove wrong the old pulp and paper chemist's adage: you can make anything from lignin except money! PMID- 26151604 TI - How Attention Changes in Response to Incentives. AB - Although the performance of simple cognitive tasks can be enhanced if an incentive is provided, the mechanisms enabling such motivational control are not known. This study sought to uncover how mechanisms of attention and readiness are altered by reward-associated incentive stimuli. We measured EEG/ERP activity as human adults viewed a high- or low-incentive cue, experienced a short preparation interval, and then performed a simple visual search task to gain the predicted reward. Search performance was faster with high versus low incentives, and this was accompanied by distinct incentive-related EEG/ERP patterns at each phase of the task (incentive, preparation, and search). First, and most surprisingly, attention to high but not low incentive cues was actively suppressed, as indexed by a PD component in response to the incentive display. During the subsequent preparation interval, neural oscillations in the alpha frequency range were reduced after high-incentive cues, indicating heightened visual readiness. Finally, attentional orienting to the target in the search array was deployed with relatively little effort on high-incentive trials, as indexed by a reduced N2pc component. These results reveal the chain of events by which the brain's executive control mechanisms respond to incentives by altering the operation of multiple processing systems to produce optimal performance. PMID- 26151605 TI - Transcranial Direct Current Stimulation of the Motor Cortex Biases Action Choice in a Perceptual Decision Task. AB - One of the multiple interacting systems involved in the selection and execution of voluntary actions is the primary motor cortex (PMC). We aimed to investigate whether the transcranial direct current stimulation (tDCS) of this area can modulate hand choice. A perceptual decision-making task was administered. Participants were asked to classify rectangles with different height-to-width ratios into horizontal and vertical rectangles using their right and left index fingers while their PMC was stimulated either bilaterally or unilaterally. Two experiments were conducted with different stimulation conditions: the first experiment (n = 12) had only one stimulation condition (bilateral stimulation), and the second experiment (n = 45) had three stimulation conditions (bilateral, anodal unilateral, and cathodal unilateral stimulations). The second experiment was designed to confirm the results of the first experiment and to further investigate the effects of anodal and cathodal stimulations alone in the observed effects. Each participant took part in two sessions. The laterality of stimulation was reversed over the two sessions. Our results showed that anodal stimulation of the PMC biases participants' responses toward using the contralateral hand whereas cathodal stimulation biases responses toward the ipsilateral hand. Brain stimulation also modulated the RT of the left hand in all stimulation conditions: Responses were faster when the response bias was in favor of the left hand and slower when the response bias was against it. We propose two possible explanations for these findings: the perceptual bias account (bottom-up effects of stimulation on perception) and the motor-choice bias account (top-down modulation of the decision-making system by facilitation of response in one hand over the other). We conclude that motor responses and the choice of hand can be modulated using tDCS. PMID- 26151606 TI - Endogenization of mouse mammary tumor virus (MMTV)-like elements in genomes of pikas (Ochotona sp.). AB - Despite the finding in European rabbit and other leporid genomes of the first ever described endogenous lentivirus and of a European rabbit exclusive endogenous gammaretrovirus, until now no exogenous retroviruses have been isolated in Lagomorpha species. Nevertheless, looking for the presence of endogenous retroviruses (ERVs) in the species genomes could lead to the discovery of retroviral lineages yet to be found in Lagomorpha. Different mammalian genomes harbor endogenous viral sequences phylogenetically close to the betaretrovirus mouse mammary tumor virus (MMTV), propelling us to look for such retroviral "fossil" in American pika (Ochotona princeps) and European rabbit (Oryctolagus cuniculus) genomes. By performing genomic mining using MMTV gag and LTR as query sequences, we found that such viral elements were absent from the European rabbit genome. Oppositely, significant matches were found in American pika, and more importantly, a nearly complete MMTV-like virus (Pika-BERV) was identified. Using Pika-BERV gag and LTR as templates, we found similar sequences endogenized in different pika (Ochotona sp.) species. The orthology of the LTR flanking region between some pika species supported shared ancestry of specific endogenous betaretroviruses, while in other pika species similar sequences, but not orthologous, should have resulted from independent insertions. Our study supports the possible existence of infecting exogenous betaretroviruses for a long term, after the divergence of Ochotonidae from Leporidae, but yet to be identified. PMID- 26151609 TI - Introduction to the Special Issue on Pediatric Sleep: Associations With Executive Functioning, ADHD, and Beyond. PMID- 26151607 TI - Three-year Outcomes in De Novo Liver Transplant Patients Receiving Everolimus With Reduced Tacrolimus: Follow-Up Results From a Randomized, Multicenter Study. AB - BACKGROUND: Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration. METHODS: In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 to (i) everolimus + reduced exposure tacrolimus (EVR + Reduced TAC), (ii) everolimus + tacrolimus elimination (TAC Elimination), or (iii) standard exposure tacrolimus (TAC Control). RESULTS: Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR) during TAC withdrawal. Of 370 patients who completed the 24 month core study on-treatment, 282 (76.2%) entered an additional 12-month extension phase. The composite efficacy failure endpoint (tBPAR, graft loss or death) occurred in 11.5% of EVR+Reduced TAC patients versus 14.6% TAC Controls from randomization to month 36 (difference, -3.2%; 95% confidence interval, 10.5% to 4.2%; P = 0.334). Treated BPAR occurred in 4.8% versus 9.2% of patients (P = 0.076). From randomization to month 36, mean (SD) estimated glomerular filtration rate decreased by 7.0 (31.3) mL/min per 1.73 m in the EVR+Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m in the TAC Control group (P = 0.005). Rates of adverse events, serious adverse events, and discontinuation due to adverse events were similar in both groups during the extension. CONCLUSIONS: A clinically relevant renal benefit after introduction of everolimus with reduced exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study, with comparable efficacy and no late safety concerns. PMID- 26151608 TI - Incidence and Outcome of C4d Staining With Tubulointerstitial Inflammation in Blood Group-incompatible Kidney Transplantation. AB - BACKGROUND: The last Banff 2013 report recognizes acute/active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection. The goal of our study was to analyze the incidence of C4d deposition after ABO-incompatible transplantation and assess outcomes in patients with ABMR, C4d staining without evidence of rejection (all acute Banff scores = 0), and C4d staining with tubulointerstitial inflammation (i > 0 with or without tubulitis). METHODS: Three months 'For cause' or protocol biopsies in 50 ABO-incompatible patients were rescored and were correlated with clinical outcomes and antibody titres. RESULTS: Active/acute ABMR was found in 23 patients (46%), C4d staining without evidence of rejection in 7 patients (14%), C4d staining with tubulointerstitial inflammation in 6 patients (12%), tubulointerstitial inflammation in 6 patients (12%), and no evidence of rejection in 8 patients (16%). Patients with active/acute ABMR had a 3-month estimated glomerular filtration rate (median,: 43 mL/min) lower than patients with no evidence of rejection (median, 61 mL/min; P = 0.01). However, after 3 months, a progressively declining estimated glomerular filtration rate was observed more frequently in patients with C4d staining and tubulointerstitial inflammation when compared to patients with no evidence of rejection (100% vs 25%, P = 0.03). Finally, independently of C4d status, interstitial inflammation occurred more frequently in patients with a pretransplant ABO antibody titre higher than 16 and/or posttransplant ABO antibody increase. CONCLUSIONS: Whereas isolated C4d deposition and isolated interstitial inflammation appear to be benign lesions, C4d deposition in association with interstitial inflammation is the biopsy finding most strongly associated with the development of chronic graft dysfunction. PMID- 26151610 TI - A Meta-Analysis of the Effect of Experimental Sleep Restriction on Youth's Attention and Hyperactivity. AB - This meta-analysis examined the effect experimental sleep restriction has on youth's attention and hyperactivity outcomes. Thirteen published studies containing 17 independent samples were included (N = 496). Random- and fixed effects models were used to estimate pooled effect sizes and moderator effects, respectively. Results indicate that sleep-restricted youth had significantly worse attention outcomes than youth with extended sleep, but no differences were evident regarding hyperactivity. Significant moderators of this effect included age and sex. These results have important implications for both the prevention and treatment of attention problems, highlighting the need for health professionals to screen for and treat underlying sleep issues. PMID- 26151611 TI - Infant Sleep Predicts Attention Regulation and Behavior Problems at 3-4 Years of Age. AB - This longitudinal study assessed the role of early sleep patterns in predicting attention regulation and behavior problems. Sleep of 43 infants was assessed using actigraphy at 12 months of age and then reassessed when the children were 3 4 years old. During this follow-up, their attention regulation and behavior problems were also assessed using a computerized test and parental reports. Lower quality of sleep in infancy significantly predicted compromised attention regulation and behavior problems. These findings underscore the need to identify and treat early sleep problems. PMID- 26151612 TI - Relations Between Toddler Sleep Characteristics, Sleep Problems, and Temperament. AB - Two sources of information (parent-reported sleep diaries and actigraph records) were used to investigate how toddler sleep characteristics (bed time/sleep onset, wake time/sleep offset, total nighttime sleep, and total sleep time) are related to sleep problems and temperament. There were 64 toddler participants in the study. Consistent with studies of older children, parent reports differed from actigraph-based records. The findings that parent-reported and actigraph-recorded sleep characteristics varied as a function of parent report of toddler sleep problems and temperament add needed information on toddler sleep. Such information may contribute to improving parents' awareness of their child's sleep characteristics and correlates of problem sleep. PMID- 26151613 TI - Less Efficient Neural Processing Related to Irregular Sleep and Less Sustained Attention in Toddlers. AB - The current study used event-related potentials to examine a candidate process through which sleep difficulties affect attentional processing in toddlers. Fifteen toddlers participated in an auditory Oddball task while neurophysiological data were collected. Sleep deficits were assessed using actigraphs, and attention was examined with a sustained attention task. A P3-like component was elicited from the toddlers, and longer target P3 latencies were associated with poorer sustained attention and irregular sleep. Findings suggest that irregular sleep is associated with less efficient attentional processing as reflected by the P3 component, and that longer target P3 latencies are associated with poorer sustained attention. PMID- 26151614 TI - Preschool Sleep Problems and Differential Associations With Specific Aspects of Executive Control in Early Elementary School. AB - This study examined the differential associations between parent-reported child sleep problems in preschool and specific aspects of executive control in early elementary school in a large sample of typically developing children (N = 215). Consistent with expectations, sleep problems were negatively associated with performance on tasks assessing working memory and interference suppression inhibition, even after controlling for general cognitive abilities, but not with flexible shifting or response inhibition. The findings add to the literature on cognitive impairments associated with pediatric sleep loss and highlight the need for early intervention for children with sleep problems to promote healthy cognitive development. PMID- 26151615 TI - Distinct Mechanisms Underlie Associations Between Forms of Childhood Maltreatment and Disruptive Nocturnal Behaviors. AB - Childhood maltreatment is associated with risk for sleep disturbances, including Disruptive Nocturnal Behaviors (DNBs). Yet, little is known regarding associations between specific forms of maltreatment and DNBs, or factors that mediate and moderate these associations. Data from a community sample of high risk youth (n = 193; M = 18.87 years old) indicated that self-reported emotional and sexual abuse during childhood made specific contributions to DNBs at the time of assessment. Trauma-related psychopathology mediated the effects of emotional abuse. Furthermore, executive function moderated the effects of sexual abuse. Findings suggest that distinct mechanisms underlie associations between maltreatment types and DNBs. PMID- 26151616 TI - Usefulness of the ratio of orbital fat to total orbit area in mild-to-moderate thyroid-associated ophthalmopathy. AB - OBJECTIVE: To identify a useful predictor of thyroid-associated ophthalmopathy (TAO) from orbital CT images; to evaluate the orbital fat and extraocular muscle area ratio as a CT-derived measure; and to investigate the correlations between this ratio and the clinical manifestations in mild-to-moderate TAO. METHODS: Between January 2012 and March 2013, 44 patients with TAO and 23 controls were studied prospectively. All of the patients underwent ophthalmic examinations, including clinical activity score, exophthalmometry, clinical photographs, alternate prism and cover test, duction and version test, Hess screen test, binocular single vision test, thyroid function tests and orbital CT. The cross sectional areas of the four rectus muscles, superior oblique muscle, optic nerve and total orbit area were calculated in the coronal view 6 mm posterior from the posterior pole of globe. RESULTS: The cross-sectional area measured on orbital CT showed increased orbital fat in patients with TAO and an increased orbital fat to total orbit area ratio (fat/orbit) in TAO with retraction and proptosis. There were significant correlations between fat/orbit and margin reflex distance 1 (p = 0.022), margin reflex distance 2 (p = 0.013) and the exophthalmometric value (p = 0.007). CONCLUSION: The orbital fat to total orbit area ratio (fat/orbit) is a useful diagnostic index in mild-to-moderate TAO. ADVANCES IN KNOWLEDGE: The orbital CT offers a useful diagnostic index in TAO. PMID- 26151617 TI - Stereotactic body radiotherapy for central lung tumours. PMID- 26151618 TI - Stereotactic body radiotherapy for central lung tumours: Author reply. PMID- 26151619 TI - DNA fragmentation in brighter sperm predicts male fertility independently from age and semen parameters. AB - OBJECTIVE: To evaluate whether sperm DNA fragmentation (sDF), measured in brighter, dimmer, and total populations, predicts natural conception, and to evaluate the intra-individual variability of sDF. DESIGN: Prospective study. SETTING: Outpatient clinic and diagnostic laboratory. PATIENT(S): A total of 348 unselected patients and 86 proven fertile men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): sDF was revealed with the use of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)/propidium iodide (PI). Receiver operating characteristic (ROC) curves were built before and after matching fertile men to patients for age (76:152) or semen parameters (68:136) or both (49:98). Intra-individual variability of sDF was assessed over 2 years. RESULT(S): Brighter (area under ROC curve [AUC] 0.718 +/- 0.54), dimmer (AUC 0.655 +/- 0.63), and total (AUC 0.757 +/- 0.54) sDF predict male fertility in unmatched and age- or semen parameters-matched subjects. After matching for both age and semen parameters, only brighter (AUC 0.711 +/- 0.83) and total (AUC 0.675 +/- 0.92) sDF predict male fertility. At high values of total sDF, brighter predicts natural conception better than total sDF. Intra-individual coefficients of variation of sDF were 9.2 +/- 8.6% (n = 25), 12.9 +/- 12.7% (n = 53), and 14.0 +/- 12.6% (n = 70) over, respectively, 100-day and 1- and 2-year periods, appearing to be the most stable of the evaluated semen parameters. CONCLUSION(S): The predictive power of total sDF partially depends on age and semen parameters, whereas brighter sDF independently predicts natural conception. Therefore, brighter sDF is a fraction of sDF that adds new information to the routine semen analysis. At high levels of sDF, distinguishing the two sperm populations improves the predictive power of sDF. Overall, our results support the idea that TUNEL/PI can be of clinical usefulness in the male fertility workup. PMID- 26151620 TI - Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial. AB - OBJECTIVE: To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. DESIGN: Randomized, prospective, double blind, placebo-controlled, crossover trial with duration of 22 weeks. SETTING: Academic medical center. PATIENT(S): Thirty pre-and postmenopausal women with sexual dysfunction. INTERVENTION(S): Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. MAIN OUTCOME MEASURE(S): Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). RESULT(S): After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. CONCLUSION(S): Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. CLINICAL TRIAL REGISTRATION NUMBER: NCT02229721. PMID- 26151621 TI - Thyroid antibodies and gestational diabetes mellitus: a meta-analysis. AB - OBJECTIVE: To determine whether thyroid antibodies are associated with an increased risk of gestational diabetes mellitus (GDM) in pregnant women. DESIGN: Meta-analysis. SETTING: Not applicable. PATIENT(S): Twenty cohort and case control studies involving pregnant women with positive thyroid antibodies were the exposure of interest, and GDM was the outcome. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A fixed-effects model was used to evaluate the relationship between thyroid antibodies and the risk of GDM. Subgroup analyses were performed among different types of study design, different thyroid antibodies, and patients with specific thyroid dysfunction. RESULT(S): The search strategy identified 167 potentially relevant publications, of which 20 were included in the meta analysis. A significant association between thyroid antibodies and GDM was observed. A meta-analysis of the 11 cohort studies with pregnant women with positive thyroid antibodies in their first trimester suggested no obvious risk of GDM compared with the reference group. In subgroup meta-analyses, no significant association between thyroid antibodies and GDM was found in euthyroid pregnant women, whereas a significant positive association was identified in women with a thyroid dysfunction. CONCLUSION(S): Based on the currently available evidence, there is a significant but not strong association between thyroid antibodies and the risk of GDM, and thyroid antibodies in the first trimester lack predictive value for the risk of GDM. In addition, thyroid antibodies may not increase the risk of GDM in euthyroid pregnant women. PMID- 26151622 TI - 1-O-acetylbritannilactone combined with gemcitabine elicits growth inhibition and apoptosis in A549 human non-small cell lung cancer cells. AB - Non-small-cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases, with a 5-year survival rate of <15%. 1-O-acetylbritannilactone (ABL), a natural chemical component obtained from inula britannica, a Chinese traditional medicine, has been demonstrated to have anticancer activity. In the present study, the antiproliferative and proapoptotic abilities of ABL alone or in combination with gemcitabine in a human NSCLC cell line were investigated. A549 cells were treated in vitro with ABL, gemcitabine, and a combination of ABL and gemcitabine for 72 h. The results demonstrated that ABL and gemcitabine inhibited cell growth and induced apoptosis of A549 cells. These effects were more potent following the combination of ABL and gemcitabine treatment than either agent alone. Furthermore, the signal transduction analysis revealed nuclear factor (NF) kappaB expression was significantly decreased by ABL and the combination treatment. The inhibitor nuclear factor kappaBalpha (IkappaBalpha) and Bax levels were upregulated whereas Bcl-2 was substantially downregulated following treatment. The present findings suggest that ABL combined with gemcitabine elicits potent apoptosis of lung cancer cells and therefore, ABL has the potential to be developed as a chemotherapeutic agent. PMID- 26151623 TI - Enantioselective [4 + 1] Annulation Reactions of alpha-Substituted Ammonium Ylides To Construct Spirocyclic Oxindoles. AB - Ammonium ylides have a long history in organic synthesis, but their application in asymmetric catalysis is still underdeveloped in regard to both substrate scope and reaction pathways compared with phosphorus and sulfur ylides. Here a previously unreported asymmetric [4 + 1] annulation reaction of 3-bromooxindoles and electron-deficient 1-azadienes has been developed through ammonium ylide catalysis of a newly designed 2'-methyl alpha-isocupreine (alpha-MeIC), efficiently delivering spirocyclic oxindole compounds incorporating a dihydropyrrole motif in excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this work represents the first example of asymmetric catalysis of ammonium ylides bearing alpha-substitutions, and the catalytic [4 + 1] annulation pathway of ammonium ylides is also unprecedented. Moreover, (1)H NMR, mass spectroscopy, and computational calculation studies were conducted, and the catalytic cycle and a tentative explanation of the enantioselective mechanism have been successfully elucidated. PMID- 26151626 TI - Structural, electronic and energetic consequences of epigenetic cytosine modifications. AB - The hydrogen bonding patterns of cytosine and its seven C5-modifed analogues paired with canonical guanine were studied using the first principle approach. Both global minima and biologically relevant conformations were studied. The former resulted from full gradient geometry optimizations of hydrogen bonded pairs, while the latter were obtained based on 125 d(GpC) dinucleotides found in the PDB database. The obtained energetic, electronic and structural data lead to the conclusion that the epigenetically relevant modification of cytosine may have serious consequences on hydrogen bonding with guanine. First of all, the significant substituent effects were observed for such trends as charges on sites involved in hydrogen bonding, the total intermolecular interaction energy or electron densities at bond critical points. Moreover, the molecular orbital polarization contribution resulting from energy decomposition expressed in terms of absolutely localized molecular orbitals exhibited an inverse linear correlation with frozen density contributions. A substituent effect on the amount of charge transfer from pyrimidine toward guanine was also observed. The increase of intermolecular interactions of guanine with modified cytosine is associated with the increase of the electro-donating character of the C5-substituent. However, only pairs involving 5-methylcytosine are more stable than those formed by canonical cytosine. Furthermore, the energy differences observed for global minima also remain important for a broad range of displacement and angular parameters defining pair conformations in model d(GpC) dinucleotides. Due to the sensitivities of intermolecular interactions to mutual arrangements of monomers the modification of cytosine at the C5 site can significantly alter the actual energy profiles. Consequently, it may be anticipated that the modified dinucleotides will adopt different conformations than a standard G-C pair in a B DNA double helix. PMID- 26151624 TI - Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells. AB - Medullary thyroid carcinoma (MTC) originates from the C-cells of the thyroid and is not sensitive to radiation or chemotherapy. Therefore, surgical removal of the tumor tissue in its entirety is the only curative treatment for MTC. The present study aimed to examine the potential mechanisms of action of extracts of Trailliaedoxa gracilis (TG; WW Smith & Forrest), a plant from the province of Sichuan, China, and of ursolic acid (UA), a pentacyclic triterpen present in TG, on the MTC-SK MTC cell line. A total of 13 TG fractions and UA were examined in vitro for their effects on cell morphology, cell number, proliferation and rates of apoptosis. Reverse transcription-quantitative polymerase chain reaction of nuclear factor-kappaB essential modifier (NEMO) was performed to delineate the role of the apoptotic pathway following treatment with UA. TG and UA were examined in vivo in xenotransplanted MTC-bearing severe combined immunodeficient mice. The TG fractions exhibited antiproliferative effects, with inhibition of mitochondrial activity in the tumor cells at concentrations, which caused no impairment of the normal control cells. The apoptotic rates of the MTC-SK cells treated with the TG fractions and UA were determined, in which no marked tumor inhibition was observed in the treated MTC-mice, and no change in the expression of NEMO was detected in the treated MTC-SK cells. The observation of early-onset activation of caspase 8 suggested that the responsible factor was linked to NEMO, an anti-apoptotic protein. However, no differences in the mRNA transcription levels of NEMO were detected in MTC-SK cells treated with UA, suggesting that this protein was not associated with the signal transducer and activator of transcription 3 pathway. PMID- 26151627 TI - Regenerative gamma-Lactone Annulations: A Modular, Iterative Approach to Oligo tetrahydrofuran Molecular Stairs and Related Frameworks. AB - A unified, stereocontrolled, regenerative gamma-butyrolactone annulation approach has been conceptualized and validated through syntheses of a range of oligo-THFs. The new protocol is short (four steps), simple (table-top reagents), and efficient (50-61% overall yields). Although the scope of this approach is unlimited, it has been demonstrated up to five iterations on commercial gamma butyrolactone to assemble six fused tetrahydrofuran moieties in a staircase-like architecture. A selection of exploratory transformations is presented to exemplify the potential applications of this protocol. PMID- 26151629 TI - The Power of Testing Memory: Basic Research and Implications for Educational Practice. AB - A powerful way of improving one's memory for material is to be tested on that material. Tests enhance later retention more than additional study of the material, even when tests are given without feedback. This surprising phenomenon is called the testing effect, and although it has been studied by cognitive psychologists sporadically over the years, today there is a renewed effort to learn why testing is effective and to apply testing in educational settings. In this article, we selectively review laboratory studies that reveal the power of testing in improving retention and then turn to studies that demonstrate the basic effects in educational settings. We also consider the related concepts of dynamic testing and formative assessment as other means of using tests to improve learning. Finally, we consider some negative consequences of testing that may occur in certain circumstances, though these negative effects are often small and do not cancel out the large positive effects of testing. Frequent testing in the classroom may boost educational achievement at all levels of education. PMID- 26151628 TI - Role of Polymer Architecture on the Activity of Polymer-Protein Conjugates for the Treatment of Accelerated Bone Loss Disorders. AB - Polymers of similar molecular weights and chemical constitution but varying in their macromolecular architectures were conjugated to osteoprotegerin (OPG) to determine the effect of polymer topology on protein activity in vitro and in vivo. OPG is a protein that inhibits bone resorption by preventing the formation of mature osteoclasts from the osteoclast precursor cell. Accelerated bone loss disorders, such as osteoporosis, rheumatoid arthritis, and metastatic bone disease, occur as a result of increased osteoclastogenesis, leading to the severe weakening of the bone. OPG has shown promise as a treatment in bone disorders; however, it is rapidly cleared from circulation through rapid liver uptake, and frequent, high doses of the protein are necessary to achieve a therapeutic benefit. We aimed to improve the effectiveness of OPG by creating OPG-polymer bioconjugates, employing reversible addition-fragmentation chain transfer polymerization to create well-defined polymers with branching densities varying from linear, loosely branched to densely branched. Polymers with each of these architectures were conjugated to OPG using a "grafting-to" approach, and the bioconjugates were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The OPG-polymer bioconjugates showed retention of activity in vitro against osteoclasts, and each bioconjugate was shown to be nontoxic. Preliminary in vivo studies further supported the nontoxic characteristics of the bioconjugates, and measurement of the bone mineral density in rats 7 days post treatment via peripheral quantitative computed tomography suggested a slight increase in bone mineral density after administration of the loosely branched OPG polymer bioconjugate. PMID- 26151630 TI - Implications of an Emerging Integration of Universal and Culturally Specific Psychologies. AB - Psychological researchers increasingly recognize that human behavior reflects a complex interplay of universal human capacities, cultural responses to unique histories and circumstances, and individual differences. Many psychological processes appear to reflect culturally specific instantiations of universal capacities. Current integrative research focuses on further clarifying definitions of universality and on refining methods for identifying universal and cultural components of psychological processes. In this article, we consider implications of this emerging integration. To illustrate possible implications for psychology, we apply it to the study of psychopathology. We report on formal models that explain why some cultures embrace dysfunction among members. We then use the integrative framework to describe methods for determining whether putative disorders bring universal or contextual life dysfunction and to clarify etiological models of three disorders. Models of psychopathology can be more informed and precise if they include careful consideration of both universal and cultural influences on behavior. PMID- 26151631 TI - Toward a New Generation of Cross-Cultural Research. AB - In this article, we describe how cross-cultural research methodologies have evolved, with each phase of research addressing limitations of a previous one. We describe briefly the three previous phases and argue for embarking on a fourth phase that empirically establishes linkages between the active cultural ingredients hypothesized to cause between-country differences and the observed differences themselves. We discuss theoretical considerations and possible empirical methods to establish such linkages, and urge researchers to seriously consider incorporating these kinds of linkage studies in their programs of research. PMID- 26151632 TI - Toward a Psychological Science for a Cultural Species. AB - Humans are a cultural species, and the study of human psychology benefits from attention to cultural influences. Cultural psychology's contributions to psychological science can largely be divided according to the two different stages of scientific inquiry. Stage 1 research seeks cultural differences and establishes the boundaries of psychological phenomena. Stage 2 research seeks underlying mechanisms of those cultural differences. The literatures regarding these two distinct stages are reviewed, and various methods for conducting Stage 2 research are discussed. The implications of culture-blind and multicultural psychologies for society and intergroup relations are also discussed. PMID- 26151633 TI - Inside the Psychologist's Studio. PMID- 26151634 TI - Modulation of Rolandic Beta-Band Oscillations during Motor Simulation of Joint Actions. AB - Successful joint actions require precise temporal and spatial coordination between individuals who aim to achieve a common goal. A growing number of behavioral data suggest that to efficiently couple and coordinate a joint task, the actors have to represent both own and the partner's actions. However it is unclear how the motor system is specifically recruited for joint actions. To find out how the goal and the presence of the partner's hand can impact the motor activity during joint action, we assessed the functional state of 16 participants' motor cortex during observation and associated motor imagery of joint actions, individual actions, and non-goal-directed actions performed with either 1 or 2 hands. As an indicator of the functional state of the motor cortex, we used the reactivity of the rolandic magnetoencephalographic (MEG) beta rhythm following median-nerve stimulation. Motor imagery combined with action observation was associated with activation of the observer's motor cortex, mainly in the hemisphere contralateral to the viewed (and at the same time imagined) hand actions. The motor-cortex involvement was enhanced when the goal of the actions was visible but also, in the ipsilateral hemisphere, when the partner's hand was visible in the display. During joint action, the partner's action, in addition to the participant's own action, thus seems to be represented in the motor cortex so that it can be triggered by the mere presence of an acting hand in the peripersonal space. PMID- 26151635 TI - Determination of Temporal Order among the Components of an Oscillatory System. AB - Oscillatory systems in biology are tightly regulated process where the individual components (e.g. genes) express in an orderly manner by virtue of their functions. The temporal order among the components of an oscillatory system may potentially be disrupted for various reasons (e.g. environmental factors). As a result some components of the system may go out of order or even cease to participate in the oscillatory process. In this article, we develop a novel framework to evaluate whether the temporal order is unchanged in different populations (or experimental conditions). We also develop methodology to estimate the order among the components with a suitable notion of "confidence." Using publicly available data on S. pombe, S. cerevisiae and Homo sapiens we discover that the temporal order among the genes cdc18; mik1; hhf1; hta2; fkh2 and klp5 is evolutionarily conserved from yeast to humans. PMID- 26151636 TI - Intracellular Analysis of the Interaction between the Human Papillomavirus Type 16 E6 Oncoprotein and Inhibitory Peptides. AB - Oncogenic types of human papillomaviruses (HPVs) cause cervical cancer and other malignancies in humans. The HPV E6 oncoprotein is considered to be an attractive therapeutic target since its inhibition can lead to the apoptotic cell death of HPV-positive cancer cells. The HPV type 16 (HPV16) E6-binding peptide pep11, and variants thereof, induce cell death specifically in HPV16-positive cancer cells. Although they do not encompass the LxxLL binding motif found in cellular HPV16 E6 interaction partners, such as E6AP, the pep11 variants strongly bind to HPV16 E6 by contacting the recently identified E6AP binding pocket. Thus, these peptides can serve as prototype E6-inhibitory molecules which target the E6AP pocket. We here analyzed their intracellular interaction with HPV16 E6. By comprehensive intracellular binding studies and GST pull-down assays, we show that E6-binding competent pep11 variants induce the formation of a trimeric complex, consisting of pep11, HPV16 E6 and p53. These findings indicate that peptides, which do not contain the LxxLL motif, can reshape E6 to enable its interaction with p53. The formation of the trimeric HPV16 E6 / peptide / p53 complex was associated with an increase of endogenous HPV16 E6 protein amounts. Yet, total cellular p53 amounts were also increased, indicating that the E6 / E6AP-mediated degradation of p53 is blocked. These findings suggest that inhibition of oncogenic activities by targeting the E6AP pocket on HPV16 E6 could be a strategy for therapeutic intervention. PMID- 26151637 TI - Food Sharing among Hadza Hunter-Gatherer Children. AB - Human prosociality is one of the defining characteristics of our species, yet the ontogeny of altruistic behavior remains poorly understood. The evolution of widespread food sharing in humans helped shape cooperation, family formation, life history, language, and the development of economies of scale. While the behavioral and ecological correlates of food sharing among adults are widely studied, very little is known about food sharing among children. Here, in the first study to analyze the food sharing patterns of hunter-gatherer children, we show that while sharing may be biased towards kin, reciprocity characterizes the majority of all sharing dyads, both related and unrelated. These data lend support to the recent claim that discrimination among kin might be linked with reciprocal altruism theory. Furthermore, we show that age positively correlates with an increase in sharing, both in frequency and amount, supporting recent suggestions that prosocial behaviors and egalitarianism develop strongly in middle childhood when children acquire the normative rules of their society. PMID- 26151638 TI - Non-Invasive Quantification of Cartilage Using a Novel In Vivo Bioluminescent Reporter Mouse. AB - Mouse models are common tools for examining post-traumatic osteoarthritis (OA), which involves cartilage deterioration following injury or stress. One challenge to current mouse models is longitudinal monitoring of the cartilage deterioration in vivo in the same mouse during an experiment. The objective of this study was to assess the feasibility for using a novel transgenic mouse for non-invasive quantification of cartilage. Chondrocytes are defined by expression of the matrix protein aggrecan, and we developed a novel mouse containing a reporter luciferase cassette under the inducible control of the endogenous aggrecan promoter. We generated these mice by crossing a Cre-dependent luciferase reporter allele with an aggrecan creERT2 knockin allele. The advantage of this design is that the targeted knockin retains the intact endogenous aggrecan locus and expresses the tamoxifen-inducible CreERT2 protein from a second IRES-driven open reading frame. These mice display bioluminescence in the joints, tail, and trachea, consistent with patterns of aggrecan expression. To evaluate this mouse as a technology for non-invasive quantification of cartilage loss, we characterized the relationship between loss of bioluminescence and loss of cartilage after induction with (i) ex vivo collagenase digestion, (ii) an in vivo OA model utilizing treadmill running, and (iii) age. Ex vivo experiments revealed that collagenase digestion of the femur reduced both luciferase signal intensity and pixel area, demonstrating a link between cartilage degradation and bioluminescence. In an in vivo model of experimental OA, we found decreased bioluminescent signal and pixel area, which correlated with pathological disease. We detected a decrease in both bioluminescent signal intensity and area with natural aging from 2 to 13 months of age. These results indicate that the bioluminescent signal from this mouse may be used as a non-invasive quantitative measure of cartilage. Future studies may use this reporter mouse to advance basic and preclinical studies of murine experimental OA with applications in synovial joint biology, disease pathogenesis, and drug delivery. PMID- 26151640 TI - Does High Self-Esteem Cause Better Performance, Interpersonal Success, Happiness, or Healthier Lifestyles? AB - Self-esteem has become a household word. Teachers, parents, therapists, and others have focused efforts on boosting self-esteem, on the assumption that high self-esteem will cause many positive outcomes and benefits-an assumption that is critically evaluated in this review. Appraisal of the effects of self-esteem is complicated by several factors. Because many people with high self-esteem exaggerate their successes and good traits, we emphasize objective measures of outcomes. High self-esteem is also a heterogeneous category, encompassing people who frankly accept their good qualities along with narcissistic, defensive, and conceited individuals. The modest correlations between self-esteem and school performance do not indicate that high self-esteem leads to good performance. Instead, high self-esteem is partly the result of good school performance. Efforts to boost the self-esteem of pupils have not been shown to improve academic performance and may sometimes be counterproductive. Job performance in adults is sometimes related to self-esteem, although the correlations vary widely, and the direction of causality has not been established. Occupational success may boost self-esteem rather than the reverse. Alternatively, self-esteem may be helpful only in some job contexts. Laboratory studies have generally failed to find that self-esteem causes good task performance, with the important exception that high self-esteem facilitates persistence after failure. People high in self-esteem claim to be more likable and attractive, to have better relationships, and to make better impressions on others than people with low self esteem, but objective measures disconfirm most of these beliefs. Narcissists are charming at first but tend to alienate others eventually. Self-esteem has not been shown to predict the quality or duration of relationships. High self-esteem makes people more willing to speak up in groups and to criticize the group's approach. Leadership does not stem directly from self-esteem, but self-esteem may have indirect effects. Relative to people with low self-esteem, those with high self-esteem show stronger in-group favoritism, which may increase prejudice and discrimination. Neither high nor low self-esteem is a direct cause of violence. Narcissism leads to increased aggression in retaliation for wounded pride. Low self-esteem may contribute to externalizing behavior and delinquency, although some studies have found that there are no effects or that the effect of self esteem vanishes when other variables are controlled. The highest and lowest rates of cheating and bullying are found in different subcategories of high self esteem. Self-esteem has a strong relation to happiness. Although the research has not clearly established causation, we are persuaded that high self-esteem does lead to greater happiness. Low self-esteem is more likely than high to lead to depression under some circumstances. Some studies support the buffer hypothesis, which is that high self-esteem mitigates the effects of stress, but other studies come to the opposite conclusion, indicating that the negative effects of low self esteem are mainly felt in good times. Still others find that high self-esteem leads to happier outcomes regardless of stress or other circumstances. High self esteem does not prevent children from smoking, drinking, taking drugs, or engaging in early sex. If anything, high self-esteem fosters experimentation, which may increase early sexual activity or drinking, but in general effects of self-esteem are negligible. One important exception is that high self-esteem reduces the chances of bulimia in females. Overall, the benefits of high self esteem fall into two categories: enhanced initiative and pleasant feelings. We have not found evidence that boosting self-esteem (by therapeutic interventions or school programs) causes benefits. Our findings do not support continued widespread efforts to boost self-esteem in the hope that it will by itself foster improved outcomes. In view of the heterogeneity of high self-esteem, indiscriminate praise might just as easily promote narcissism, with its less desirable consequences. Instead, we recommend using praise to boost self-esteem as a reward for socially desirable behavior and self-improvement. PMID- 26151639 TI - Nasopharyngeal Epstein-Barr Virus Load: An Efficient Supplementary Method for Population-Based Nasopharyngeal Carcinoma Screening. AB - Serological detection of Epstein-Barr virus (EBV) antibodies is frequently used in nasopharyngeal carcinoma (NPC) mass screening. However, the large number of seropositive subjects who require close follow-up is still a big burden. The present study aimed to detect the nasopharyngeal EBV load in a high-risk population seropositive for antibodies against EBV, as well as to examine whether assay for nasopharyngeal EBV DNA load might reduce the number of high-risk subjects for follow-up and improve early detection of NPC. A prospective and population-based cohort study was conducted in southern China from 2006 through 2013. Among 22,186 participants, 1045 subjects with serum immunoglobulin A (IgA) antibodies against viral capsid antigen (VCA) titers >= 1:5 were defined as high risk group, and were then followed-up for NPC occurrence. Qualified nasopharyngeal swab specimens were available from 905 participants and used for quantitative PCR assay. Our study revealed that 89% (802/905) subjects showed positive EBV DNA in nasopharyngeal swab. The nasopharyngeal EBV load in females was higher than that in males. The nasopharyngeal EBV load increased with increasing serum VCA/IgA titers. Eight cases of newly diagnosed NPC showed an extremely elevated EBV load, and 87.5% (7 of 8 patients) were early-stage NPCs. The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8 * 10(6) copies/swab [range 4.8 * 10(4)-1.1 * 10(8)] vs. 5.6 * 10(3) [range 0-3.8 * 10(6)]). Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895). In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening program in high-risk populations. PMID- 26151641 TI - The fate of nano-silver in aqueous media. AB - Silver nanoparticles offer highly attractive properties for many applications, however concern has been raised over the possible toxicity of this material in environmental systems. While it is thought that the release of Ag(+) can play a crucial role in this toxicity, the mechanism by which the oxidative dissolution of nano-silver occurs is not yet understood. Here we address this through the electrochemical analysis of gold-core silver-shell nanoparticles in various solutions. This novel method allows the direct quantification of silver dissolution by normalisation to the gold core signal. This is shown to be highly effective at discriminating between silver dissolution and the loss of nanoparticles from the electrode surface. We evidence through this rigorous approach that the reduction of O2 drives the dissolution of nano-silver, while in the presence of Cl(-) this dissolution is greatly inhibited. This work is extended to the single nanoparticle level using nano-impact experiments. PMID- 26151642 TI - Atomic arrangement and electron band structure of Si(1 1 1)-beta-?3 x ?3-Bi reconstruction modified by alkali-metal adsorption: ab initio study. AB - Using ab initio calculations, atomic structure and electronic properties of Si(1 1 1)[Formula: see text]-Bi surface modified by adsorption of 1/3 monolayer of alkali metals, Li, Na, K, Rb and Cs, have been explored. Upon adsorption of all metals, a similar atomic structure develops at the surface where twisted chained Bi trimers are arranged into a honeycomb network and alkali metal atoms occupy the [Formula: see text] sites in the center of each honeycomb unit. Among other structural characteristics, the greatest variation concerns the relative heights at which alkali metals reside with respect to Bi-trimer layer. Except for Li, the other metals reside higher than Bi layer and their heights increase with atomic number. All adsorbed surface structures display similar electron band structures of which the most essential feature is metallic surface-state band with a giant spin splitting. This electronic property allows one to consider the Si(1 1 1)[Formula: see text]-Bi surfaces modified by alkali metal adsorption as a set of material systems showing promise for spintronic applications. PMID- 26151643 TI - Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails. AB - Ceramides are indispensable constituents of the stratum corneum (SC), the uppermost impermeable layer of human skin. Ceramides with shorter (four- to eight carbon acyl chains) fatty acid chains increase skin and model membrane permeability, while further shortening of the chain leads to increased resistance to penetration almost as good as that of ceramides from healthy skin (24 carbons long on average). Here we address the extent to which the atomistic CHARMM36 and coarse-grain MARTINI molecular dynamics (MD) simulations reflect the skin permeability data. As a result, we observed the same bell-shaped permeability trend for water that was observed in the skin and multilayer membrane experiments for model compounds. We showed that the enhanced permeability of the short ceramides is mainly caused by the disturbance of their headgroup conformation because of their inability to accommodate the shorter lipid acyl chain into a typical hairpin conformation, which further led to their destabilization and phase separation. As MD simulations described well delicate structural features of SC membranes, they seem to be suitable for further studies of the SC superstructure, including the development of skin penetration enhancers for transdermal drug delivery and skin toxicity risk assessment studies. PMID- 26151645 TI - Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients. AB - Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research. PMID- 26151647 TI - Biocomposites from Natural Rubber: Synergistic Effects of Functionalized Cellulose Nanocrystals as Both Reinforcing and Cross-Linking Agents via Free Radical Thiol-ene Chemistry. AB - Natural rubber/cellulose nanocrystals (NR/CNCs) form true biocomposites from renewable resources and are demonstrated to show significantly improved thermo mechanical properties and reduced stress-softening. The nanocomposites were prepared from chemically functionalized CNCs bearing thiols. CNCs served as both reinforcing and cross-linking agents in the NR matrix, and the study was designed to prove the cross-linking function of modified CNCs. CNCs were prepared from cotton, and the cross-linkable mercapto-groups were introduced onto the surface of CNCs by esterification. Nanocomposite films were prepared by dispersing the modified CNCs (m-CNCs) in NR matrix by solution casting. The cross-links at the filler-matrix (m-CNCs-NR) interface were generated by photochemically initiated thiol-ene reactions as monitored by real-time FTIR analysis. The synergistic effects of reinforcement and chemical cross-linking at the m-CNCs-NR interface on structure, thermo-mechanical, and stress-softening behavior were investigated. Methods included field emission scanning electron microscopy (FE-SEM), swelling tests, dynamic mechanical analysis, and tensile tests. Compared to biocomposites from NR with unmodified CNCs, the NR/m-CNCs nanocomposites showed 2.4-fold increase in tensile strength, 1.6-fold increase in strain-to-failure, and 2.9 fold increase in work-of-fracture at 10 wt % of m-CNCs in NR. PMID- 26151644 TI - Genomic potential for arsenic efflux and methylation varies among global Prochlorococcus populations. AB - The globally significant picocyanobacterium Prochlorococcus is the main primary producer in oligotrophic subtropical gyres. When phosphate concentrations are very low in the marine environment, the mol:mol availability of phosphate relative to the chemically similar arsenate molecule is reduced, potentially resulting in increased cellular arsenic exposure. To mediate accidental arsenate uptake, some Prochlorococcus isolates contain genes encoding a full or partial efflux detoxification pathway, consisting of an arsenate reductase (arsC), an arsenite-specific efflux pump (acr3) and an arsenic-related repressive regulator (arsR). This efflux pathway was the only previously known arsenic detox pathway in Prochlorococcus. We have identified an additional putative arsenic mediation strategy in Prochlorococcus driven by the enzyme arsenite S-adenosylmethionine methyltransferase (ArsM) which can convert inorganic arsenic into more innocuous organic forms and appears to be a more widespread mode of detoxification. We used a phylogenetically informed approach to identify Prochlorococcus linked arsenic genes from both pathways in the Global Ocean Sampling survey. The putative arsenic methylation pathway is nearly ubiquitously present in global Prochlorococcus populations. In contrast, the complete efflux pathway is only maintained in populations which experience extremely low PO4:AsO4, such as regions in the tropical and subtropical Atlantic. Thus, environmental exposure to arsenic appears to select for maintenance of the efflux detoxification pathway in Prochlorococcus. The differential distribution of these two pathways has implications for global arsenic cycling, as their associated end products, arsenite or organoarsenicals, have differing biochemical activities and residence times. PMID- 26151646 TI - College student mental health and quality of workplace relationships. AB - OBJECTIVE: The goal of this study was to examine the effect of quality of workplace relationships on the mental health of employed undergraduates, with work-related variables as a potential mechanism. PARTICIPANTS: Participants were 170 employed students (76% female, average age = 19.9) recruited in March 2011. Most worked part-time and had been at their jobs over a year. METHODS: Students were recruited from an undergraduate introductory psychology course and completed online surveys about the quality of workplace relationships, mental health (ie, somatic stress symptoms, depression, anxiety, and life satisfaction), and work related variables (ie, job satisfaction, support, turnover and burnout). RESULTS: Students who reported having workplace relationships with co-occurring positivity and negativity had worse self-reported mental health outcomes than students reporting having wholly positive relationships. The relationship between workplace relationship quality and mental health was mediated by negative work related variables. CONCLUSIONS: Workplace relationships-even in part-time employment settings-influence college students' mental health. PMID- 26151648 TI - The effect of cluster size on the optical band gap energy of Zn-based metal organic frameworks. AB - We have synthesized three Metal-Organic Frameworks (MOFs) in which Zn metal ions form the secondary building unit, and 4,4'-sulfonyldibenzoic acid (SDB) serves as the ligand: [[Zn(DMF)(SDB)](DMF), 1, [Zn(3)(DMF)(3)(SDB)(3)](DMF), 2 and [Zn(3)(OH)(2)(SDB)(2)] (DMF)(2), 3, where DMF = dimethyl formamide]. Compound contains a paddle-wheel type Zn dimer, compound contains a Zn trimer motif, and contains a one-dimensional Zn-OH-Zn chain. These building units may be considered to be Zn clusters. We have measured and theoretically calculated the band gap energy and by theoretical investigations we found that the cluster size plays an important role in the band gap energy, however additional effects are observed. The larger cluster size corresponds to a larger band gap energy, however the cavity of the trimer based compound (2) traps a solvent molecule that decreases the band gap energy. PMID- 26151649 TI - Determination of elemental baseline using peltigeralean lichens from Northeastern Canada (Quebec): Initial data collection for long term monitoring of the impact of global climate change on boreal and subarctic area in Canada. AB - Northeastern Canada is mostly free of anthropogenic activities. The extent to which this territory has been impacted by anthropogenic atmospheric depositions remains to be studied. The main goal of our study was to establish background levels for metals in boreal muscicolous/terricolous macrolichens over non urbanized areas of northeastern Canada (Quebec). Concentrations of 18 elements (Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, Cd, and Pb) were determined for three species of the genus Peltigera (Peltigera aphthosa (L.) Willd. s.l., Peltigera neopolydactyla (Gyeln.) Gyeln. s.l., Peltigera scabrosa Th. Fr. s.l.), and Nephroma arcticum (L.) Torss., along a 1080 km south-north transect and along a of 730 km west-east transect. We report that elemental contents in the sampled lichen thalli are very low and similar to background levels found in other studies performed in pristine places (high elevation or remote ecosystems) throughout the world. Overall, our results demonstrate that most of the boreal and subarctic zone of Quebec (northeastern Canada) is still pristine. The elemental baseline established in these lichen populations will contribute to monitor metal pollution in boreal and sub-polar ecosystems due to global climate change and future industrial expansion. PMID- 26151650 TI - Is atherosclerotic disease associated with organic components of ambient fine particles? AB - Heart disease is a major killer in western societies; coronary artery disease and atherosclerosis are important contributors to this mortality. Atherosclerosis in mice with a deleted apoE gene (apoE-/-) is accelerated by exposure to ambient ultrafine particles (UFP) which are particles smaller than 180 nm in diameter. UFP contain organic components that are pro-oxidant and may cause or aggravate heart disease. Could removal of these organic constituents mitigate adverse cardiovascular effects? ApoE-/- mice were exposed to concentrated UFP (CAP), CAP from which organic constituents were removed by thermal denuding (deCAP) or purified air (controls) for 5 hr/day, 4 days/week for 8 weeks. Heart rate (HR), heart rate variability (HRV), biomarkers of oxidative stress and the sizes of arterial plaques were measured. Adverse effects were seen in CAP-exposed mice (increased size of arterial plaque, increased oxidative stress and decreased HRV, compared to controls). Adverse effects were not observed in deCAP-exposed mice. Removal of organic constituents from ambient particles resulted in significant reduction of toxic cardiovascular effects of air pollution exposure. PMID- 26151651 TI - Characterization of green zero-valent iron nanoparticles produced with tree leaf extracts. AB - In the last decades nanotechnology has become increasingly important because it offers indisputable advantages to almost every area of expertise, including environmental remediation. In this area the synthesis of highly reactive nanomaterials (e.g. zero-valent iron nanoparticles, nZVI) is gaining the attention of the scientific community, service providers and other stakeholders. The synthesis of nZVI by the recently developed green bottom-up method is extremely promising. However, the lack of information about the characteristics of the synthetized particles hinders a wider and more extensive application. This work aims to evaluate the characteristics of nZVI synthesized through the green method using leaves from different trees. Considering the requirements of a product for environmental remediation the following characteristics were studied: size, shape, reactivity and agglomeration tendency. The mulberry and pomegranate leaf extracts produced the smallest nZVIs (5-10 nm), the peach, pear and vine leaf extracts produced the most reactive nZVIs while the ones produced with passion fruit, medlar and cherry extracts did not settle at high nZVI concentrations (931 and 266 ppm). Considering all tests, the nZVIs obtained from medlar and vine leaf extracts are the ones that could present better performances in the environmental remediation. The information gathered in this paper will be useful to choose the most appropriate leaf extracts and operational conditions for the application of the green nZVIs in environmental remediation. PMID- 26151652 TI - Input of organic matter enhances degradation of weathered diesel fuel in sub tropical sediments. AB - We investigated different types of biostimulation practices to enhance degradation of weathered conventional diesel fuel in sandy beach sediments from coastal Alabama. Biodegradation rates were measured following the addition of either inorganic nutrients, or organic matter derived from either plant material (Spartina alterniflora) or fish tissue (Chloroscombrus chrysurus) both common to the region. The greatest hydrocarbon degradation rates were observed in the C. chrysurus amended treatments (k=0.0119 d(-1)). Treatment with fish-derived organic matter increased the degradation rates by 104% as compared to control treatments, while inorganic nutrient addition increased the degradation rates by 57%. The addition of plant derived organic matter, however, only marginally enhanced the degradation rates (~7%) during the course of the study. Bacterial 16S rRNA analyses revealed that most sediment microorganisms belonged to the classes; Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Bacteroidetes. The most frequently abundant hydrocarbon degraders were mostly similar to Achromobater sp., Microbulbifer sp., Ruegeria sp., and Pseudomonas sp. PMID- 26151653 TI - Rare earth elements in the aragonitic shell of freshwater mussel Corbicula fluminea and the bioavailability of anthropogenic lanthanum, samarium and gadolinium in river water. AB - High-technology metals - such as the rare earth elements (REE) - have become emerging contaminants in the hydrosphere, yet little is known about their bioavailability. The Rhine River and the Weser River in Germany are two prime examples of rivers that are subjected to anthropogenic REE input. While both rivers carry significant loads of anthropogenic Gd, originating from contrast agents used for magnetic resonance imaging, the Rhine River also carries large amounts of anthropogenic La and lately Sm which are discharged into the river from an industrial point source. Here, we assess the bioavailability of these anthropogenic microcontaminants in these rivers by analyzing the aragonitic shells of the freshwater bivalve Corbicula fluminea. Concentrations of purely geogenic REE in shells of comparable size cover a wide range of about one order of magnitude between different sampling sites. At a given sampling site, geogenic REE concentrations depend on shell size, i.e. mussel age. Although both rivers show large positive Gd anomalies in their dissolved loads, no anomalous enrichment of Gd relative to the geogenic REE can be observed in any of the analyzed shells. This indicates that the speciations of geogenic and anthropogenic Gd in the river water differ from each other and that the geogenic, but not the anthropogenic Gd is incorporated into the shells. In contrast, all shells sampled at sites downstream of the industrial point source of anthropogenic La and Sm in the Rhine River show positive La and Sm anomalies, revealing that these anthropogenic REE are bioavailable. Only little is known about the effects of long-term exposure to dissolved REE and their general ecotoxicity, but considering that anthropogenic Gd and even La have already been identified in German tap water and that anthropogenic La and Sm are bioavailable, this should be monitored and investigated further. PMID- 26151654 TI - Modeling tribal exposures to methyl mercury from fish consumption. AB - Exposure assessment and risk management considerations for tribal fish consumption are different than for the general U.S. population because of higher fish intake from subsistence fishing and/or from unique cultural practices. This research summarizes analyses of available data and methodologies for estimating tribal fish consumption exposures to methyl mercury (MeHg). Large MeHg fish tissue data sets from the Environmental Protections Agency's (EPA's) Office of Water, USGS's EMMMA program, and other data sources, were integrated, analyzed, and combined with fish intake (consumption) data for exposure analyses using EPA's SHEDS-Dietary model. Results were mapped with GIS tools to depict spatial distributions of the MeHg in fish tissues and fish consumption exposure patterns. Contribution analyses indicates the major sources for those exposures, such as type and length of fish, geographical distribution (water bodies), and dietary exposure patterns. Sensitivity analyses identify the key variables and exposure pathways. Our results show that MeHg exposure of tribal populations from fish are about 3 to 10 times higher than the US general population and that exposure poses potential health risks. The estimated risks would be reduced as much as 50%, especially for high percentiles, just by avoiding consumption of fish species with higher MeHg concentrations such as walleye and bowfin, even without changing total fish intake. These exposure assessment methods and tools can help inform decisions regarding meal sizes and frequency, types of fish and water bodies to avoid, and other factors to minimize exposures and potential health risks from contaminated fish on tribal lands. PMID- 26151655 TI - Temporal evolution of bacterial communities associated with the in situ wetland based remediation of a marine shore porphyry copper tailings deposit. AB - Mine tailings are a serious threat to the environment and public health. Remediation of these residues can be carried out effectively by the activation of specific microbial processes. This article presents detailed information about temporal changes in bacterial community composition during the remediation of a section of porphyry copper tailings deposited on the Bahia de Ite shoreline (Peru). An experimental remediation cell was flooded and transformed into a wetland in order to prevent oxidation processes, immobilizing metals. Initially, the top oxidation zone of the tailings deposit displayed a low pH (3.1) and high concentrations of metals, sulfate, and chloride, in a sandy grain size geological matrix. This habitat was dominated by sulfur- and iron-oxidizing bacteria, such as Leptospirillum spp., Acidithiobacillus spp., and Sulfobacillus spp., in a microbial community which structure resembled acid mine drainage environments. After wetland implementation, the cell was water-saturated, the acidity was consumed and metals dropped to a fraction of their initial respective concentrations. Bacterial communities analyzed by massive sequencing showed time dependent changes both in composition and cell numbers. The final remediation stage was characterized by the highest bacterial diversity and evenness. Aside from classical sulfate reducers from the phyla delta-Proteobacteria and Firmicutes, community structure comprised taxa derived from very diverse habitats. The community was also characterized by an elevated proportion of rare phyla and unaffiliated sequences. Numerical ecology analysis confirmed that the temporal population evolution was driven by pH, redox, and K. Results of this study demonstrated the usefulness of a detailed follow-up of the remediation process, not only for the elucidation of the communities gradually switching from autotrophic, oxidizing to heterotrophic and reducing living conditions, but also for the long term management of the remediation wetlands. PMID- 26151656 TI - Applying an ecosystem service approach to unravel links between ecosystems and society in the coast of central Chile. AB - Ecosystem-based management implies understanding feedbacks between ecosystems and society. Such understanding can be approached with the Drivers-Pressures-State change-Impacts-Response framework (DPSIR), incorporating stakeholders' preferences for ecosystem services to assess impacts on society. This framework was adapted to six locations in the central coast of Chile, where artisanal fisheries coexist with an increasing influx of tourists, and a set of fisheries management areas alternate with open access areas and a no-take Marine Protected Area (MPA). The ecosystem services in the study area were quantified using biomass and species richness in intertidal and subtidal areas as biological indicators. The demand for ecosystem services was elicited by interviews to the principal groups of users. Our results evidenced decreasing landings and a negative perception of fishermen on temporal trends of catches. The occurrence of recreational fishing was negligible, although the consumption of seafood by tourists was relatively high. Nevertheless, the consumption of organisms associated to the study system was low, which could be linked, amongst other factors, to decreasing catches. The comparison of biological indicators between management regimens provided variable results, but a positive effect of management areas and the MPA on some of the metrics was observed. The prioritising of ecosystem attributes by tourists was highly homogenous across the six locations, with "scenic beauty" consistently selected as the preferred attribute, followed by "diversity". The DPSIR framework illustrated the complex interactions existing in these locations, with weak linkages between society's priorities, existing management objectives and the state of biological communities. Overall, this work improved our knowledge on relations between components of coastal areas in central Chile, of paramount importance to advance towards an ecosystem-based management in the area. PMID- 26151657 TI - Modelling and assessment of the impact of radiocesium and radiostrontium contamination in the Thermaikos Gulf, Greece. AB - A radiological model for (137)Cs and (90)Sr dispersion in the marine environment of the Thermaikos Gulf, Greece, and the river catchments draining into the Gulf, is presented. The model, developed and implemented within the MOIRA-PLUS decision support system, integrates appropriate site-specific information. The model's performance has been tested using the available empirical (137)Cs activity concentration data in abiotic and biotic components of the gulf since the Chernobyl accident. Further, this paper describes the results of a modelling exercise performed within the IAEA's EMRAS II international modelling programme to estimate the environmental sensitivity of this characteristic Mediterranean coastal marine environment following radioactive contamination. The radiation doses to humans after a single hypothetical instantaneous deposition of 1000 Bq m(-2), assuming that all of their food intake from the marine pathway comes from the local environment, were calculated. The obtained results are consistent with estimates from other models for different coastal marine environments in the frame of the above-mentioned EMRAS exercise. PMID- 26151658 TI - Deep-ocean foraging northern elephant seals bioaccumulate persistent organic pollutants. AB - As top predators in the northeast Pacific Ocean, northern elephant seals (Mirounga angustirostris) are vulnerable to bioaccumulation of persistent organic pollutants (POPs). Our study examined a suite of POPs in blubber (inner and outer) and blood (serum) of free-ranging northern elephant seals. For adult females (N=24), we satellite tracked and sampled the same seals before and after their approximately seven month long foraging trip. For males, we sampled different adults and sub-adults before (N=14) and after (N=15) the same foraging trip. For females, we calculated blubber burdens for all compounds. The highest POP concentrations in males and females were found for ?DDTs and ?PCBs. In blubber and serum, males had significantly greater concentrations than females for almost all compounds. For males and females, ?DDT and ?PBDEs were highly correlated in blubber and serum. While ?PCBs were highly correlated with ?DDTs and ?PBDEs in blubber and serum for males, ?PCBs showed weaker correlations with both compounds in females. As females gained mass while foraging, concentrations of nearly all POPs in inner and outer blubber significantly decreased; however, the absolute burden in blubber significantly increased, indicating ingestion of contaminants while foraging. Additionally, we identified three clusters of seal foraging behavior, based on geography, diving behavior, and stable carbon and nitrogen isotopes, which corresponded with differences in ?DDTs, ?PBDEs, MeO-BDE 47, as well as the ratio of ?DDTs to ?PCBs, indicating the potential for behavior to heighten or mitigate contaminant exposure. The greatest concentrations of ?DDTs and ?PBDEs were observed in the cluster that foraged closer to the coast and had blood samples more enriched in (13)C. Bioaccumulation of POPs by elephant seals supports mesopelagic food webs as a sink for POPs and highlights elephant seals as a potential sentinel of contamination in deep ocean food webs. PMID- 26151659 TI - Air quality impacts and health-benefit valuation of a low-emission technology for rail yard locomotives in Atlanta Georgia. AB - One of the largest rail yard facilities in the Southeastern US, the Inman and Tilford yards, is located in the northwestern section of Atlanta, Georgia alongside other industries, schools, businesses, and dwellings. It is a significant source of fine particulate (PM2.5) and black carbon (BC) (Galvis, Bergin, & Russell, 2013). We calculate 2011 PM2.5 and BC emissions from the rail yards and primary industrial and on-road mobile sources in the area and determine their impact on local air quality using Gaussian dispersion modeling. We determine the change in PM2.5 and BC concentrations that could be accomplished by upgrading traditional switcher locomotives used in these rail yards to a lower emitting technology and evaluate the health benefits for comparison with upgrade costs. Emissions from the rail yards were estimated using reported fuel consumption data (GAEPD, 2012b) and emission factors previously measured in the rail yards (Galvis et al., 2013). Model evaluation against 2011 monitoring data found agreement between measured and simulated concentrations. Model outputs indicate that the line-haul and switcher activities are responsible for increments in annual average concentrations of approximately 0.5+/-0.03 MUg/m(3) (39%) and 0.7+/-0.04 MUg/m(3) (56%) of BC, and for 1.0+/-0.1 MUg/m(3) (7%) and 1.6+/-0.2 MUg/m(3) (14%) of PM2.5 at two monitoring sites located north and south of the rail yards respectively. Upgrading the switcher locomotives at the yards with a lower emitting technology in this case "mother slug" units could decrease PM2.5 and BC emissions by about 9 and 3 t/year respectively. This will lower annual average PM2.5 concentrations between 0.3+/-0.1 MUg/m(3) and 0.6+/-0.1 MUg/m(3) and BC concentrations between 0.1+/-0.02 MUg/m(3) and 0.2+/-0.03 MUg/m(3) at monitoring sites north and south of the rail yards respectively, and would facilitate PM2.5 NAAQS attainment in the area. We estimate that health benefits of approximately 20 million dollars per year could be gained. PMID- 26151660 TI - Catechol-based layer-by-layer assembly of composite coatings: a versatile platform to hierarchical nano-materials. AB - Inspired by the marine mussel's ability to adhere to surfaces underwater, an aqueous catechol-based dip coating platform was developed. Using a catechol functionalized polyacrylamide binder in combination with inorganic nanoparticles enables the facile fabrication of robust composite coatings via a layer-by-layer process. This modular assembly of well-defined building blocks provides a versatile alternative to electrostatic driven approaches with layer thickness and refractive indices being readily tunable. The platform nature of this approach enables the fabrication of hierarchically ordered nano-materials such as Bragg stacks. PMID- 26151662 TI - Riproximin: A type II ribosome inactivating protein with anti-neoplastic potential induces IL24/MDA-7 and GADD genes in colorectal cancer cell lines. AB - Riproximin (Rpx) is a type II ribosome inactivating protein, which was extracted and purified from the seeds of Ximenia americana. Previous studies demonstrated cytotoxicity of Rpx against a variety of cell lines originating from solid and non-solid cancers. In this study, we investigated the mechanistic aspects of Rpx in selected human and rat colorectal cancer (CRC) cell lines. Cytotoxic levels of Rpx were determined by MTT assay, while cytostatic and apoptotic effects were investigated by flow cytometry and nuclear staining procedures. Effects of Rpx exposure on colony formation/migration of CRC cells and expressional modulations in anticancer/stress-related genes were also studied. Rpx showed significant and comparable levels of cytotoxicity in CRC cells as determined by inhibitory concentration (IC) values. Similar inhibitory effects were found for clonogenicity, while more pronounced inhibition of migration was observed in response to Rpx exposure. Profound arrest in S phases of the cell cycle was noted especially in primary CRC cells. Apoptotic effects were more prominent in rat CRC cells as indicated by Annexin V-FITC assay and Hoechst 33342 nuclear staining. Rpx exposure induced significantly increased levels of the IL24/MDA-7, a well characterized anticancer gene, in all CRC cells. In addition, following Rpx treatment, high expression levels of growth arrest and DNA damage (GADD family) genes were also observed. Increased expression of two additional GADD genes (34 and 153) only in rat CRC cells (CC531) conferred higher sensitivity towards Rpx and subsequent anti-proliferative/apoptotic effects as compared to human CRC cells (SW480 and SW620). The present investigation indicates the anticancer potential of Rpx in CRC and favor further evaluation of this natural compound as therapeutic agent. PMID- 26151661 TI - Isotope-Coded Labeling for Accelerated Protein Interaction Profiling Using MS. AB - Protein interaction surface mapping using MS is widely applied but comparatively resource-intensive. Here, a workflow adaptation for use of isotope-coded tandem mass tags for the purpose is reported. The key benefit of improved throughput derived from sample acquisition multiplexing and automated analysis is shown to be maintained in the new application. Mapping of the epitopes of two monoclonal antibodies on their respective targets serves to illustrate the novel approach. We conclude that the approach enables mapping of interactions by MS at significantly larger scales than hereto possible. PMID- 26151663 TI - Activation of ARK5/miR-1181/HOXA10 axis promotes epithelial-mesenchymal transition in ovarian cancer. AB - Epithelial ovarian cancer (EOC) is the sixth most common cancer in females worldwide and, although advances have been made in the detection, diagnosis and therapies for EOC, it remains the most lethal gynecologic malignancy in advanced countries. Nevertheless, relatively little is known concerning the molecular events that lead to the development of this highly aggressive disease. Elucidating the molecular mechanism involved in this disease may prove useful to understand the pathogenesis and progression of the disease, and to identify new targets for effective therapies. In the present study, we examined the role of ARK5 in ovarian cancer and normal matched tissues using western blot analysis and migration and invasion, and wound-healing assays. The results showed that ARK5 was upregulated in ovarian cancer tissues, compared with adjacent normal tissues. Moreover, it promoted epithelial-mesenchymal transition (EMT) and inhibited miR 1181 expression in ovarian cancer cells. Subsequent investigations showed that miR-1181 promoted mesenchymal-epithelial transition (MET) in ovarian cancer cells. Downstream target genes of miR-1181 were searched, and it was identified that miR-1181 degraded HOXA10 by targeting its 3' untranslated region (3'UTR) in ovarian cancer cells. The results confirmed that HOXA10 promoted EMT in ovarian cancer cells. Thus, activation of the ARK5/miR-1181/HOXA10 axis may be positively associated with EMT in ovarian cancer. PMID- 26151664 TI - Use of quality assessment tools in systematic reviews was varied and inconsistent. AB - OBJECTIVES: To assess the use of quality assessment tools among a cross-section of systematic reviews (SRs) and to further evaluate whether quality was used as a parameter in the decision to include primary studies within subsequent meta analysis. STUDY DESIGN AND SETTING: We searched PubMed for SRs (interventional, observational, and diagnostic) published in Core Clinical Journals between January 1 and March 31, 2014. RESULTS: Three hundred nine SRs were identified. Quality assessment was undertaken in 222 (71.8%) with isolated use of the Cochrane risk of bias tool (26.1%, n = 58) and the Newcastle-Ottawa Scale (15.3%, n = 34) most common. A threshold level of primary study quality for subsequent meta-analysis was used in 12.9% (40 of 309) of reviews. Overall, fifty-four combinations of quality assessment tools were identified with a similar preponderance of tools used among observational and interventional reviews. Multiple tools were used in 11.7% (n = 36) of SRs overall. CONCLUSION: We found that quality assessment tools were used in a majority of SRs; however, a threshold level of quality for meta-analysis was stipulated in just 12.9% (n = 40). This cross-sectional analysis provides further evidence of the need for more active or intuitive editorial processes to enhance the reporting of SRs. PMID- 26151665 TI - Extrapolation will never replace randomized clinical trials. PMID- 26151666 TI - MiR-138 suppresses airway smooth muscle cell proliferation through the PI3K/AKT signaling pathway by targeting PDK1. AB - BACKGROUND: Airway smooth muscle cells (ASMCs) play important physiological roles in the lung, and their abnormal proliferation directly contributes to airway remodeling during development of lung diseases such as asthma. MicroRNAs are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation, but little is known about the precise role of microRNAs in the proliferation of ASMCs. METHODS: In this study, human ASMCs from asthmatic and non-asthmatic donors were used. MicroRNA and mRNA expression were measured by quantitative real-time PCR. Dual-luciferase reporter assays were performed to determine whether microRNA-138 (miR-138) binds directly to 3-phosphoinositide-dependent protein kinase-1(PDK1) 3' untranslated region (3' UTR) to alter gene expression. RESULTS: The results showed that overexpression of miR-138 reduced proliferation of human ASMCs, whereas inhibition of miR-138 increased proliferation of ASMCs. MiR-138 directly suppressed PDK1 expression by targeting the 3'-UTR of the gene. MiR-138 controls ASMC proliferation through directly inhibiting the phosphoinositide 3-kinase (PI3K) pathway. CONCLUSIONS: Our study indicated that miR-138 regulation of PI3K signaling in ASMCs by altering the expression of PDK1 can have a profound impact on cell proliferation. PMID- 26151667 TI - Maternal mosaicism for a large segmental duplication of 18q as a secondary finding following non-invasive prenatal testing and implications for test accuracy. PMID- 26151668 TI - A comparison of multivariate and univariate time series approaches to modelling and forecasting emergency department demand in Western Australia. AB - OBJECTIVE: To develop multivariate vector-ARMA (VARMA) forecast models for predicting emergency department (ED) demand in Western Australia (WA) and compare them to the benchmark univariate autoregressive moving average (ARMA) and Winters' models. METHODS: Seven-year monthly WA state-wide public hospital ED presentation data from 2006/07 to 2012/13 were modelled. Graphical and VARMA modelling methods were used for descriptive analysis and model fitting. The VARMA models were compared to the benchmark univariate ARMA and Winters' models to determine their accuracy to predict ED demand. The best models were evaluated by using error correction methods for accuracy. RESULTS: Descriptive analysis of all the dependent variables showed an increasing pattern of ED use with seasonal trends over time. The VARMA models provided a more precise and accurate forecast with smaller confidence intervals and better measures of accuracy in predicting ED demand in WA than the ARMA and Winters' method. CONCLUSION: VARMA models are a reliable forecasting method to predict ED demand for strategic planning and resource allocation. While the ARMA models are a closely competing alternative, they under-estimated future ED demand. PMID- 26151669 TI - Synthesis of Selected Cationic Pnictanes [LnPnX3-n](n+) (L = Imidazolium-2-yl; Pn = P, As; n = 1-3) and Replacement Reactions with Pseudohalogens. AB - Herein we report on reactions of "imidazoliumyl-transfer" reagents [L((R/R'))SiMe3][OTf] (4((R/R'))[OTf]); L = imidazolium-2-yl, R/R': Me/Me, (i)Pr/Me, Dipp/H, Dipp/Cl) with pnictogen trichlorides PnCl3 (Pn = P, As, Sb) in various stoichiometries. In the case of the 1:1 reaction of [L((R/R'))SiMe3][OTf] with PCl3 the corresponding cationic imidazoliumyl-substituted dichlorophosphanes [L((R/R'))PCl2](+) (1P((R/R')))(+) are obtained as triflate salts on a multigram scale. We found that the reactions using various stoichiometries of [L((R/R'))SiMe3][OTf] and PnCl3 are less selective in the case of the heavier congeners or by decreasing steric demand of the R-group attached to the N atoms of the heterocycle. An equilibrium between the monocation [L((Me/Me))PCl2](+) (1P((Me/Me)+)), the dication [L((Me/Me))2PCl](2+) (2P((Me/Me)2+)), and the trication [L((Me/Me))3P](3+) (5P((Me/Me)3+)) is observed in solution. Reactions of the monocationic derivatives [L((R/R'))PnCl2][OTf] (Pn = P, As) with Me3SiX (X = CN, N3) resulted in the exchange of the chloro groups for the respective pseudohalogen and yielded the dicyano [L((R/R'))Pn(CN)2][OTf] (6Pn((R/R'))[OTf]) and diazido-substituted pnictanes [L((R/R'))Pn(N3)2][OTf] (7Pn((R/R'))[OTf]), respectively. All new compounds are thoroughly characterized by multinuclear NMR, IR, and Raman spectroscopy. For most cases the molecular structure was confirmed by X-ray crystal structure analysis. PMID- 26151670 TI - Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation. AB - A new paradigm for cellulose depolymerization by fungi focuses on an oxidative mechanism involving cellobiose dehydrogenases (CDH) and copper-dependent lytic polysaccharide monooxygenases (LPMO); however, mechanistic studies have been hampered by the lack of structural information regarding CDH. CDH contains a haem binding cytochrome (CYT) connected via a flexible linker to a flavin-dependent dehydrogenase (DH). Electrons are generated from cellobiose oxidation catalysed by DH and shuttled via CYT to LPMO. Here we present structural analyses that provide a comprehensive picture of CDH conformers, which govern the electron transfer between redox centres. Using structure-based site-directed mutagenesis, rapid kinetics analysis and molecular docking, we demonstrate that flavin-to-haem interdomain electron transfer (IET) is enabled by a haem propionate group and that rapid IET requires a closed CDH state in which the propionate is tightly enfolded by DH. Following haem reduction, CYT reduces LPMO to initiate oxygen activation at the copper centre and subsequent cellulose depolymerization. PMID- 26151672 TI - On the dimensionality of odor space. AB - There is great interest in understanding human olfactory experience from a principled and quantitative standpoint. The comparison is often made to color vision, where a solid framework with a three-dimensional perceptual space enabled a rigorous search for the underlying neural pathways, and the technological development of lifelike color display devices. A recent, highly publicized report claims that humans can discriminate at least 1 trillion odors, which exceeds by many orders of magnitude the known capabilities of color discrimination. This claim is wrong. I show that the failure lies in the mathematical method used to infer the size of odor space from a limited experimental sample. Further analysis focuses on establishing how many dimensions the perceptual odor space has. I explore the dimensionality of physical, neural, and perceptual spaces, drawing on results from bacteria to humans, and propose some experimental approaches to better estimate the number of discriminable odors. PMID- 26151671 TI - Mitotic fidelity requires transgenerational action of a testis-restricted HP1. AB - Sperm-packaged DNA must undergo extensive reorganization to ensure its timely participation in embryonic mitosis. Whereas maternal control over this remodeling is well described, paternal contributions are virtually unknown. In this study, we show that Drosophila melanogaster males lacking Heterochromatin Protein 1E (HP1E) sire inviable embryos that undergo catastrophic mitosis. In these embryos, the paternal genome fails to condense and resolve into sister chromatids in synchrony with the maternal genome. This delay leads to a failure of paternal chromosomes, particularly the heterochromatin-rich sex chromosomes, to separate on the first mitotic spindle. Remarkably, HP1E is not inherited on mature sperm chromatin. Instead, HP1E primes paternal chromosomes during spermatogenesis to ensure faithful segregation post-fertilization. This transgenerational effect suggests that maternal control is necessary but not sufficient for transforming sperm DNA into a mitotically competent pronucleus. Instead, paternal action during spermiogenesis exerts post-fertilization control to ensure faithful chromosome segregation in the embryo. PMID- 26151673 TI - The number of olfactory stimuli that humans can discriminate is still unknown. AB - It was recently proposed (Bushdid et al., 2014) that humans can discriminate between at least a trillion olfactory stimuli. Here we show that this claim is the result of a fragile estimation framework capable of producing nearly any result from the reported data, including values tens of orders of magnitude larger or smaller than the one originally reported in (Bushdid et al., 2014). Additionally, the formula used to derive this estimate is well-known to provide an upper bound, not a lower bound as reported. That is to say, the actual claim supported by the calculation is in fact that humans can discriminate at most one trillion olfactory stimuli. We conclude that there is no evidence for the original claim. PMID- 26151675 TI - Complex layered dental restorations: Are they recognizable and do they survive extreme conditions? AB - Recent research has shown that restorative dental materials can be recognized by microscopy and elemental analysis (scanning electron microscopy/energy dispersive X-ray spectroscopy and X-ray fluorescence; SEM/EDS and XRF) and that this is possible even in extreme conditions, such as cremation. These analytical methods and databases of dental materials properties have proven useful in DVI (disaster victim identification) of a commercial plane crash in 2009, and in a number of other victim identification cases. Dental materials appear on the market with ever expanding frequency. With their advent, newer methods of restoration have been proposed and adopted in the dental office. Methods might include placing multiple layers of dental materials, where they have different properties including adhesion, viscosity, or working time. These different dental materials include filled adhesives, flowable resins, glass ionomer cements, composite resins, liners and sealants. With possible combinations of different materials in these restorations, the forensic odontologist is now confronted with a new difficulty; how to recognize each individual material. The question might be posed if it is even possible to perform this task. Furthermore, an odontologist might be called upon to identify a victim under difficult circumstances, such as when presented with fragmented or incinerated remains. In these circumstances the ability to identify specific dental materials could assist in the identification of the deceased. Key to use of this information is whether these new materials and methods are detailed in the dental chart. Visual or radiographic inspection may not reveal the presence of a restoration, let alone the possible complex nature of that restoration. This study demonstrates another scientific method in forensic dental identification. PMID- 26151674 TI - Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state. AB - Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity. PMID- 26151676 TI - Efficacy and Safety of Abiraterone Acetate in Elderly (75 Years or Older) Chemotherapy Naive Patients with Metastatic Castration Resistant Prostate Cancer. AB - PURPOSE: Metastatic castration resistant prostate cancer primarily affects elderly men. In this post hoc analysis we investigated the safety and efficacy of abiraterone acetate in elderly (age 75 years or greater) and younger (less than 75 years) patient subgroups at the prespecified interim analysis (55% of total overall survival events) for the COU-AA-302 (Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients with Metastatic Castration-Resistant Prostate Cancer) trial. MATERIALS AND METHODS: Patients were stratified and randomized 1:1 to abiraterone acetate 1,000 mg plus prednisone/prednisolone 5 mg twice daily (abiraterone-prednisone) vs placebo plus prednisone/prednisolone 5 mg twice daily (prednisone alone). Co-primary end points were radiographic progression-free and overall survival. Median time to event and HR were estimated using the Kaplan Meier method and a Cox model, respectively. RESULTS: A total of 350 elderly patients treated with abiraterone-prednisone had significant improvements in overall and radiographic progression-free survival vs those with prednisone alone (HR 0.71, 95% CI 0.53-0.96 vs HR 0.63, 95% CI 0.48-0.83), similar to 738 younger patients (HR 0.81, 95% CI 0.63-1.03 vs HR 0.49, 95% CI 0.40-0.59). All secondary end points favored the abiraterone-prednisone arm for both age subgroups. Specific adverse events with abiraterone-prednisone were similar between the age subgroups. Elderly patients in both treatment arms had higher rates of fluid retention and cardiac disorders than younger patients, although rates of dose reduction or treatment interruptions due to adverse events were low in both age subgroups. CONCLUSIONS: Abiraterone acetate demonstrated clinical benefit and was well tolerated in elderly and younger men with chemotherapy naive, metastatic castration resistant prostate cancer. Thus, findings support it as a treatment option for elderly patients who may not tolerate other therapies with greater toxicity. PMID- 26151677 TI - Gonadotropin-releasing hormone inhibits the proliferation and motility of nasopharyngeal carcinoma cells. AB - Gonadotropin-releasing hormone (GnRH), or its analogues have been demonstrated to exhibit anti-proliferative effects on tumour cells in ovarian, endometrial and breast cancer through GnRH-receptors (GnRH-R). However, the role of GnRH in nasopharyngeal carcinoma (NPC) remains to be elucidated. In order to investigate the effects of GnRH in NPC, the present study examined the expression of the GnRH R transcript in NPC and investigated the phenotypic changes in HK1 cells, a recurrent NPC-derived cell line, upon receiving GnRH treatment. Firstly, the GnRH R transcript was demonstrated in the NPC cell lines and four snap frozen biopsies using reverse transcription-quantitative polymerase chain reaction. In addition, immunohistochemistry revealed the expression of GnRH-R in two of the eight (25%) NPC specimens. Treatment with GnRH induced a rapid increase in intracellular ionised calcium concentration in the NPC cells. GnRH and its agonists, triptorelin and leuprolide, exerted anti-proliferative effects on the NPC cells, as determined using an MTS assay. GnRH did not induce any cell cycle arrest in the HK1 cells under the conditions assessed in the present study. Time-lapse imaging demonstrated a reduction in cell motility in the GnRH-treated cells. In conclusion, GnRH, or its analogues may have antitumour effects on NPC cells. The consequences of alterations in the levels of GnRH on the progression of NPC require further examination. PMID- 26151678 TI - The minimal work cost of information processing. AB - Irreversible information processing cannot be carried out without some inevitable thermodynamical work cost. This fundamental restriction, known as Landauer's principle, is increasingly relevant today, as the energy dissipation of computing devices impedes the development of their performance. Here we determine the minimal work required to carry out any logical process, for instance a computation. It is given by the entropy of the discarded information conditional to the output of the computation. Our formula takes precisely into account the statistically fluctuating work requirement of the logical process. It enables the explicit calculation of practical scenarios, such as computational circuits or quantum measurements. On the conceptual level, our result gives a precise and operational connection between thermodynamic and information entropy, and explains the emergence of the entropy state function in macroscopic thermodynamics. PMID- 26151679 TI - Neural circuit dysfunction in schizophrenia: Insights from animal models. AB - Despite decades of research, the neural circuit abnormalities underlying schizophrenia remain elusive. Although studies on schizophrenia patients have yielded important insights they have not been able to fully reveal the details of how neural circuits are disrupted in the disease, which is essential for understanding its pathophysiology and developing new treatment strategies. Animal models of schizophrenia are likely to play an important role in this effort. Such models allow neural circuit dysfunction to be investigated in detail and the role of risk factors and pathophysiological mechanisms to be experimentally assessed. The goal of this review is to summarize what we have learned from electrophysiological studies that have examined neural circuit function in animal models of schizophrenia. Although these studies have revealed diverse manifestations of neural circuit dysfunction spanning multiple levels of analysis, common themes have nevertheless emerged across different studies and animal models, revealing a core set of neural circuit abnormalities. These include an imbalance between excitation and inhibition, deficits in synaptic plasticity, disruptions in local and long-range synchrony and abnormalities in dopaminergic signaling. The relevance of these findings to the pathophysiology of the disease is discussed, as well as outstanding questions for future research. PMID- 26151680 TI - Chronic maternal hyperglycemia induced during mid-pregnancy in rats increases RAGE expression, augments hippocampal excitability, and alters behavior of the offspring. AB - Maternal diabetes during pregnancy may increase the risk of neurodevelopmental disorders in the offspring by increasing inflammation. A major source of inflammatory signaling observed in diabetes is activation of the receptor for advanced glycation end-products (RAGE), and increased RAGE expression has been reported in psychiatric disorders. Thus, we sought to examine whether maternal diabetes creates a proinflammatory state, triggered largely by RAGE signaling, that alters normal brain development and behavior of the offspring. We tested this hypothesis in rats using the streptozotocin (STZ; 50mg/kg; i.p.) model of diabetes induced during mid-pregnancy. Following STZ treatment, we observed a significant increase in RAGE protein expression in the forebrain of the offspring (postnatal day 1). Data obtained from whole-cell patch clamping of hippocampal neurons in cultures from the offspring of STZ-treated dams revealed a striking increase in excitability. When tested in a battery of behavioral tasks in early adulthood, the offspring of STZ-treated dams had significantly lower prepulse inhibition, reduced anxiety-like behavior, and altered object-place preference when compared to control offspring. In an operant-based strategy set-shifting task, STZ offspring did not differ from controls on an initial visual discrimination or reversal learning but took significantly longer to shift to a new strategy (i.e., set-shift). Insulin replacement with an implantable pellet in the dams reversed the effects of maternal diabetes on RAGE expression, hippocampal excitability, prepulse inhibition and object-place memory, but not anxiety-like behavior or set-shifting. Taken together, these results suggest that chronic maternal hyperglycemia alters normal hippocampal development and behavior of the offspring, effects that may be mediated by increased RAGE signaling in the fetal brain. PMID- 26151682 TI - Molecular and functional profiling of histamine receptor-mediated calcium ion signals in different cell lines. AB - Calcium ions (Ca(2+)) play a pivotal role in cellular physiology. Often Ca(2+) dependent processes are studied in commonly available cell lines. To induce Ca(2+) signals on demand, cells may need to be equipped with additional proteins. A prominent group of membrane proteins evoking Ca(2+) signals are G-protein coupled receptors (GPCRs). These proteins register external signals such as photons, odorants, and neurotransmitters and convey ligand recognition into cellular responses, one of which is Ca(2+) signaling. To avoid receptor cross talk or cross-activation with introduced proteins, the repertoire of cell endogenous receptors must be known. Here we examined the presence of histamine receptors in six cell lines frequently used as hosts to study cellular signaling processes. In a concentration-dependent manner, histamine caused a rise in intracellular Ca(2+) in HeLa, HEK 293, and COS-1 cells. The concentration for half-maximal activation (EC50) was in the low micromolar range. In individual cells, transient Ca(2+) signals and Ca(2+) oscillations were uncovered. The results show that (i) HeLa, HEK 293, and COS-1 cells express sufficient amounts of endogenous receptors to study cellular Ca(2+) signaling processes directly and (ii) these cell lines are suitable for calibrating Ca(2+) biosensors in situ based on histamine receptor evoked responses. PMID- 26151681 TI - Adjuvant Systemic Therapy in Older Breast Cancer Women: Can We Optimize the Level of Care? AB - Defining optimal adjuvant treatment for older women with breast cancer is challenged by the lack of level-1 clinical evidence and the heterogeneity of the older population. Nevertheless, recommendations based on reviews of available evidence mainly from retrospective subgroup analyses and extrapolation of study results from younger patients, and expert opinions, may be useful to guide treatment decisions in fit patients. But how can we properly define a "fit" older patient? In clinical practice, age by itself and clinical impression generally drive treatment decision, although the appropriateness of this judgment is under documented. Such an approach risks overtreatment or, more frequently, undertreatment. A geriatric assessment can be valuable in oncology practice to address this issue. In this review article, we will focus only on systemic treatment and will discuss "standard" adjuvant systemic treatment strategies for fit older breast cancer patients and the role of "personalized" systemic therapy in unfit patients. The concepts conveyed in this review cannot be extrapolated to locoregional therapy. PMID- 26151684 TI - Development of a cell-based screening method for compounds that inhibit or are transported by large neutral amino acid transporter 1, a key transporter at the blood-brain barrier. AB - Large neutral amino acid transporter 1 (LAT1) transports neutral amino acids with aromatic or branched side chains as well as their derivatives or prodrugs. Because the transporter is highly expressed at the blood-brain barrier and in some tumor cells, it is a potential target to treat brain disease and cancer. Therefore, it is essential to develop a method to screen for LAT1 inhibitors or for therapeutic compounds that it can transport. In this study, one such method was developed that combines an in vitro cell-based assay with high-throughput ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC QQQ-MS). Using this method, candidate compounds could be tested for the ability to inhibit or to compete with uptake of gabapentin, an LAT1 substrate, in HT-29 cells, which abundantly express the transporter. Gabapentin uptake is measured by mass spectrometry, which requires as little as 6min/sample and will enable analysis of large numbers of samples. We anticipate that the method will be useful to identify LAT1 inhibitors or substrates without the need for animals or radioactive labeling. PMID- 26151683 TI - Label-free DNA sequencing using Millikan detection. AB - A label-free method for DNA sequencing based on the principle of the Millikan oil drop experiment was developed. This sequencing-by-synthesis approach sensed increases in bead charge as nucleotides were added by a polymerase to DNA templates attached to beads. The balance between an electrical force, which was dependent on the number of nucleotide charges on a bead, and opposing hydrodynamic drag and restoring tether forces resulted in a bead velocity that was a function of the number of nucleotides attached to the bead. The velocity of beads tethered via a polymer to a microfluidic channel and subjected to an oscillating electric field was measured using dark-field microscopy and used to determine how many nucleotides were incorporated during each sequencing-by synthesis cycle. Increases in bead velocity of approximately 1% were reliably detected during DNA polymerization, allowing for sequencing of short DNA templates. The method could lead to a low-cost, high-throughput sequencing platform that could enable routine sequencing in medical applications. PMID- 26151685 TI - Enhancing the Performances of P3HT:PCBM-MoS3-Based H2-Evolving Photocathodes with Interfacial Layers. AB - Organic semiconductors have great potential for producing hydrogen in a durable and economically viable manner because they rely on readily available materials and can be solution-processed over large areas. With the objective of building efficient hybrid organic-inorganic photoelectrochemical cells, we combined a noble-metal-free and solution-processable catalyst for proton reduction, MoS3, and a poly(3-hexylthiophene):phenyl-C61-butyric acid methyl ester (P3HT:PCBM) bulk heterojunction (BHJ). Different interfacial layers were investigated to improve the charge transfer between P3HT:PCBM and MoS3. Metallic Al/Ti interfacial layers led to an increase of the photocurrent by up to 8 mA cm(-2) at reversible hydrogen electrode (RHE) potential with a 0.6 V anodic shift of the H2 evolution reaction onset potential, a value close to the open-circuit potential of the P3HT:PCBM solar cell. A 50-nm-thick C60 layer also works as an interfacial layer, with a current density reaching 1 mA cm(-2) at the RHE potential. Moreover, two recently highlighted1 figures-of-merit, measuring the ratio of power saved, Phisaved,ideal and Phisaved,NPAC, were evaluated and discussed to compare the performances of various photocathodes assessed in a three-electrode configuration. Phisaved,ideal and Phisaved,NPAC use the RHE and a nonphotoactive electrode with an identical catalyst as the dark electrode, respectively. They provide different information especially for differentiation of the roles of the photogenerating layer and catalyst. The best results were obtained with the Al/Ti metallic interlayer, with Phisaved,ideal and Phisaved,NPAC reaching 0.64% and 2.05%, respectively. PMID- 26151687 TI - van Hove Singularity Enhanced Photochemical Reactivity of Twisted Bilayer Graphene. AB - Twisted bilayer graphene (tBLG) exhibits van Hove singularities (VHSs) in the density of states that can be tuned by changing the twist angle (theta), sparking various novel physical phenomena. Much effort has been devoted to investigate the theta-dependent physical properties of tBLG. Yet, the chemical properties of tBLG with VHSs, especially the chemical reactivity, remain unexplored. Here we report the first systematic study on the chemistry of tBLG through the photochemical reaction between graphene and benzoyl peroxide. Twisted bilayer graphene exhibits theta-dependent reactivity, and remarkably enhanced reactivity is obtained when the energy of incident laser matches with the energy interval of the VHSs of tBLG. This work provides an insight on the chemistry of tBLG, and the successful enhancement of chemical reactivity derived from VHS is highly beneficial for the controllable chemical modification of tBLG as well as the development of tBLG based devices. PMID- 26151688 TI - Serum levels of nitrate, nitrite and advanced oxidation protein products (AOPP) in patients with nonalcoholic fatty liver disease. AB - BACKGROUND: Oxidative stress is increased and anti-oxidant defense mechanisms are impaired in patients with hepatosteatosis. The aim of the present study was to evaluate the serum levels of several oxidant and anti-oxidant markers in patients with nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: Thirty-four patients with NAFLD, and 19 healthy controls were included. In this study, we measured serum nitrate and advanced oxidation protein product (AOPP) as the oxidizing products and nitrite as the anti-oxidizing marker. Nitrate and nitrite levels were measured using a calorimetric method, and levels of serum AOPP were measured by a spectrophotometric method using a commercial ELISA kit. RESULTS: Serum nitrate and AOPP levels were significantly higher in the NAFLD group compared to the control group. Serum nitrite and N-N levels were similar between the two groups. Serum nitrate and N-N levels were found to be significantly higher in patients with elevated ALT levels compared to patients with normal ALT levels. Serum nitrite and AOPP levels were comparable between these groups. Mean platelet volume (MPV) was significantly lower in the NAFLD group compared to the control group. CONCLUSIONS: Serum levels of oxidizing agents including nitrate and AOPP increase in patients with NAFLD. In contrast, serum nitrite, an antioxidant agent, does not adequately increase to compensate for the oxidizing effects in these patients. PMID- 26151686 TI - Gene therapy for ocular diseases meditated by ultrasound and microbubbles (Review). AB - The eye is an ideal target organ for gene therapy as it is easily accessible and immune-privileged. With the increasing insight into the underlying molecular mechanisms of ocular diseases, gene therapy has been proposed as an effective approach. Successful gene therapy depends on efficient gene transfer to targeted cells to prove stable and prolonged gene expression with minimal toxicity. At present, the main hindrance regarding the clinical application of gene therapy is not the lack of an ideal gene, but rather the lack of a safe and efficient method to selectively deliver genes to target cells and tissues. Ultrasound-targeted microbubble destruction (UTMD), with the advantages of high safety, repetitive applicability and tissue targeting, has become a potential strategy for gene- and drug delivery. When gene-loaded microbubbles are injected, UTMD is able to enhance the transport of the gene to the targeted cells. High-amplitude oscillations of microbubbles act as cavitation nuclei which can effectively focus ultrasound energy, produce oscillations and disruptions that increase the permeability of the cell membrane and create transient pores in the cell membrane. Thereby, the efficiency of gene therapy can be significantly improved. The UTMD-mediated gene delivery system has been widely used in pre-clinical studies to enhance gene expression in a site-specific manner in a variety of organs. With reasonable application, the effects of sonoporation can be spatially and temporally controlled to improve localized tissue deposition of gene complexes for ocular gene therapy applications. In addition, appropriately powered, focused ultrasound combined with microbubbles can induce a reversible disruption of the blood-retinal barrier with no significant side effects. The present review discusses the current status of gene therapy of ocular diseases as well as studies on gene therapy of ocular diseases meditated by UTMD. PMID- 26151689 TI - Association between serum vitamin D and parathyroid hormone levels in Turkish patients with colonic polyps. AB - Epidemiological and investigational studies have proved that vitamin D is important in autoimmune processes and has anticancerogenic properties. But the interplay between serum vitamin D and parathyroid hormone (PTH) in colorectal polyps has been less clearly put forward. We evaluated serum vitamin D, PTH levels in Turkish people and tried to stratify colorectal polyps according to risk factors. Patients undergoing colonoscopy between January 2012 and March 2012 were considered to study serum vitamin D levels during winter. Study population comprised of 98 colorectal polyp and 197 normal colonoscopy patients. RESULTS: Serum vitamin D levels were not different between the groups (mean vitamin D level in polyp group 14.3 +/- 11.1 vs. 12.7 +/- 6.74 the normal group, p = 0.12). Likewise serum PTH levels were not different between the groups Patients with polyps were further classified as high and low risk polyps. When discriminant function analysis was conducted, the effects of vitamin D or PTH levels were not again significant. During the study period 16 colorectal carcinoma cases were detected. Serum vitamin D or PTH levels were not significantly different between colorectal cancer or overall study group patients. Finally serum vitamin D levels were stratified into quartiles. Likewise there was not any significant difference between the groups. The present study suggests that serum vitamin D and PTH levels were not different between colorectal polyp and control groups. And serum vitamin D levels were significantly low in both groups suggesting a significant vitamin D deficient state in Turkish patients. PMID- 26151690 TI - New insight to IL-23/IL-17 axis in Iranian infected adult patients with gastritis: effects of genes polymorphisms on expression of cytokines. AB - BACKGROUND AND OBJECTIVE: Chronic inflammation is the hallmark of the pathogenesis of H. pylori-induced gastric cancer. IL-17A and IL-17F are inflammatory cytokines expressed by a novel subset of CD4+Th cells and play critical function in inflammation. We evaluated the relationship between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with IL-6, IL-17, IL-21, IL 23 and TGF-beta1 mRNAs expression in regard to H. pylori infection with chronic gastritis. MATERIAL AND METHODS: Total RNA and genomic DNA were extracted from gastric biopsies of 58 H. pylori-infected patient with gastritis. Afterward, mucosal IL-6, IL-17, IL-21, IL-23 and TGF-beta1 mRNAs expression and polymorphisms in IL-17A G197A, IL-17F A7488G and IL-23R +2199A/Cin gastric biopsies were determined by real-time PCR and PCR-RFLP. RESULTS: Our results show that IL-17A G197A, IL-17F A7488G andIL23R +2199A/C polymorphisms have no effect on mucosal expression of IL-6, IL-17, IL-21 and TGF-beta1 mRNAs expression in H. pylori-infected patients with chronic gastritis. CONCLUSIONS: These results suggest that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms no alter mucosal cytokine pattern in Iranian patients with H. pylori-associated gastritis diseases. PMID- 26151691 TI - Calcium level may be a predictive factor for pseudocyst formation after acute pancreatitis. AB - Pancreatic pseudocysts (PPs) are defined as fluid collections more than 4 weeks old that are surrounded by a nonepithelial wall of fibrous or granulation tissue. Many risk factors have been associated with pseudocyst development but predictive factors remain to be explored. The aim of this study was to investigate the clinical, and biochemical parameters that may predict the development of a PPs after an attack of acute pancreatitis (AP). The medical charts of 102 patients diagnosed with AP were enrolled into the study. Demographic, clinical and laboratory details were recorded at admission and at the 48(th) hour. There were several risk factors on admission and at the 48(th) hour that was predictive of PP formation when evaluated by univariate analysis such as: Alanine aminotransferase level at 48 hrs, calcium level at admission, base excess at 48 hrs, calcium level at 48 hrs, and albumin level at 48 hrs. In multivariate analysis, low calcium level at admission was the only variable that was shown to predict formation of PPs. Lower serum calcium level may be a predictive factor for the development of PPs after AP attack. We advise that patients with calcium levels below 8 mg/dl, after AP should be followed more closely. PMID- 26151692 TI - Role of lymphatic vessel density in colorectal cancer: prognostic significance and clinicopathologic correlations. AB - BACKGROUNDS AND AIMS: Over the past decades the identification of several molecules that are expressed specifically in the lymphatic endothelial cells has resulted in marked advances in the field of lymphangiogenesis. We aimed to measure LVD in colorectal cancer patients and to compare it with microvascular density (MVD) - a marker of angiogenesis - and patients' clinicopathological parameters and survival, as the measurement of lymphatic vessel density (LVD) has been documented in various tumor types, including colorectal cancer. PATIENTS AND METHODS: Fifty one patients who had undergone surgical resection for stage I-III colorectal cancer entered this study. LVD and MVD were determined immunohistochemically with the use of D2-40 and CD34 antibody respectively. The evaluation of LVD was performed by both visual and computer-aided image analysis. RESULTS: The majority of lymphatic vessels were located in the peritumoral areas rather than within the tumor. The results obtained from the image analyzer correlated significantly with the data obtained using visual counting with light microscopy. Both visual and image analysis LVD failed to correlate with patients' age and gender and tumor location, stage, grade, MVD count and survival. CONCLUSIONS: The biologic role of the lymphatic vasculature in tumor progression remains controversial. The present study failed to associate LVD with outcome markers and prognosis and further studies would be required to verify our results. PMID- 26151693 TI - The Disease Burden of Hepatitis C in Belgium : An update of a realistic disease control strategy. AB - BACKGROUND: This manuscript serves as an update to position papers published in 2014 based on the available Belgian hepatitis C virus (HCV) epidemiological data. METHODS: Building on the current standard of care (2015 : 900 >= F3 patients treated with 70-85% SVR), four new scenarios were developed to achieve the goals of near viral elimination and prevention of HCV associated morbidity and mortality by 2026 and 2031. Increases in treatment efficacy were assumed in 2016 (90% SVR) and 2017 (95% SVR). RESULTS: Scenario 1: Treating 6,670 patients annually by 2018 (>= F0 beginning in 2017) and diagnosing 3,790 patients annually by 2020, a 90% reduction in viremic cases and advanced outcomes was observed by 2026. Scenario 2: Treating 4,300 patients annually by 2018 (>= F0 beginning in 2020) without increasing the number diagnosed, a 90% reduction in viremic cases and 85%-95% reduction in advanced outcomes was observed by 2031. Scenario 3: Treating 5,000 >= F2 patients annually by 2018, and diagnosing 3,620 patients annually by 2020, a 90% reduction in advanced outcomes and 50% reduction in viremic cases was observed by 2026. Scenario 4: Treating 3,100 >= F2 patients annually by 2018 without increasing the number diagnosed, a 90%-95% reduction in advanced outcomes and 55% reduction in viremic cases was observed by 2031. CONCLUSIONS: Scenario 2 would provide the most favorable balance of outcomes (90% reduction in viremic prevalence and advanced outcomes) and realistic requirements for implementation (gradual increase in treatment, delayed incorporation of patients with no/mild fibrosis). PMID- 26151694 TI - Severe acute hepatitis following intravenous amiodarone : a case report and review of the literature. AB - BACKGROUND AND AIMS: Hepatotoxic complications of long-term oral amiodarone therapy have been well described ; however, liver injury secondary to parenteral infusion of amiodarone is uncommon, potentially fatal, and poorly understood. The hepatotoxicity is thought to result from the diluent polysorbate 80 and not the amiodarone its self. Theories suggest an allergic or immunologic response leading to alterations in the hepatocellular membrane while some propose that ischemia, not a drug reaction, is truly to blame. METHODS: Both the PubMed and Embase databases were searched for cases of acute hepatitis implicating intravenous amiodarone with a total of 25 cases from 1986 to 2012 identified. Each case was then carefully evaluated to determine the connection between parenteral amiodarone and acute hepatotoxicity while assessing for evidence of potential ischemia. RESULTS: Of the 25 published cases of amiodarone induced acute hepatotoxicity available for review, only 10 provide evidence to conclusively implicate parenteral amiodarone as the etiology. We add the eleventh reported case of parenteral amiodarone induced acute severe hepatitis to the literature and report the most comprehensive review of this topic to date. CONCLUSIONS: There is sufficient evidence to support amiodarone induced acute hepatotoxicity as a unique entity separate from ischemic hepatitis. If suspected, parenteral amiodarone should be discontinued and held indefinitely. PMID- 26151695 TI - A case of chronic recurrent multifocal osteomyelitis associated with crohn's disease. AB - Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease of unknown etiology, most commonly affecting the metaphysis of long bones, especially the tibia, femur and clavicle. The clinical spectrum varies from self-limited uni-or multi-focal lesions to chronic recurrent courses. Diagnosis is based on clinical, radiologic and pathological findings, is probably underdiagnosed due to poor recognition of the disease. A dysregulated innate immunity causes immune cell infiltration of the bones with subsequent osteoclast activation leading to sterile bone lesions. The molecular pathophyiology is still incompletely understood but association with other auto-inflammatory diseases such as inflammatory bowel disease (IBD), psoriasis, Wegener's disease, arthritis and synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is interesting. CRMO can precede the symptoms of the associated disease by several years. The bone remodeling caused by CRMO can cause permanent disability. We report the case of a 10-year-old boy with CRMO in association with Crohn's disease. PMID- 26151696 TI - CMV gastritis in the immunocompetent host. PMID- 26151697 TI - Retrograde dilation of a complex radiation-induced esophageal stricture through percutaneous gastrostomy. AB - Upper esophageal strictures occur in approximately 3-4% of patients who receive radiotherapy for head and neck cancers. The standart initial treatment is dilation by using bougie or through-the-scope balloon dilators. Endoscopic treatment requires the passage of a guidewire through the stricture which cannot be accomplished in some of the patients with complex strictures. Retrograde dilation of esophageal strictures through a mature percutaneous gastrostomy tract have been reported in a limited number of cases and small case series up to date and can be considered as a rescue treatment before considering surgery in such patients. Herein we report retrograde dilatation of a radiation-induced complex esophageal stricture through the percutaneous gastrostomy tract in a patient with operated larynx cancer. PMID- 26151698 TI - Characteristic imaging findings of duodenal perforation. AB - Two patients were admitted to emergency room with complaint of abdominal pain with abrupt onset and retroperitoneal free air was detected in pararenal area on CT. In this paper, characteristic CT findings of patients diagnosed with duodenal perforation are presented under the light of literature data. PMID- 26151699 TI - Leukoclastic vasculitis extending from esophagus to terminal ileum. AB - Leucocytoclastic vasculitis (LCV) is commonly presented as a skin disease by affecting the small vessels of targeted area. Containing loops of vessels with end- capillaries makes the small intestine villus potantially target area of LcV, when obstructed with immune complexes. PMID- 26151700 TI - Splenic abscess in ulcerative colitis under anti tumor necrosis factor treatment. AB - Splenic abscess are rare conditions. Since morbidity and mortality rates are high, immediate diagnosis should be required. Here we presented an ulcerative colitis patients who develops splenic abscess under anti tumor necrosis factor treatment. PMID- 26151701 TI - Black esophagus and duodenal perforation : more than an incidental association. PMID- 26151702 TI - Hepatitis B resolution after autologous Bone Marrow Transplantation. PMID- 26151703 TI - Efficiency of rifampicin in emergency treatment of severe hyperbilirubinemia : report of two cases and review of literature. AB - We showed in this study that rifampicin therapy is more effective than plasmapheresis and steroid treatment in diseases associated with severe hyperbilirubinemia. In our opinion, rifampicin treatment may suitable especially for patients with persistent hyperbilirubinemia, and it would be appropriate to use rifampicin as a challenge therapy to patients with severe hyperbilirubinemia, but liver function tests in these patients must be monitored closely. PMID- 26151704 TI - A rare pylorus outlet anomaly : Pylorus on incissura angularis. PMID- 26151706 TI - Computed tomography guided percutaneous transapical closure of cardiac apex after prosthetic mitral paravalvular leak closure. PMID- 26151705 TI - Bolaamphiphiles as carriers for siRNA delivery: From chemical syntheses to practical applications. AB - In this study we have investigated a new class of cationic lipids- "bolaamphiphiles" or "bolas"--for their ability to efficiently deliver small interfering RNAs (siRNAs) to cancer cells. The bolas of this study consist of a hydrophobic chain with one or more positively charged head groups at each end. Recently, we reported that micelles of the bolas GLH-19 and GLH-20 (derived from vernonia oil) efficiently deliver siRNAs, while having relatively low toxicities in vitro and in vivo. Our previous studies validated that; bolaamphiphiles can be designed to vary the magnitude of siRNA shielding, its delivery, and its subsequent release. To further understand the structural features of bolas critical for siRNAs delivery, new structurally related bolas (GLH-58 and GLH-60) were designed and synthesized from jojoba oil. Both bolas have similar hydrophobic domains and contain either one, in GLH-58, or two, in GLH-60 positively charged head groups at each end of the hydrophobic core. We have computationally predicted and experimentally validated that GLH-58 formed more stable nano sized micelles than GLH-60 and performed significantly better in comparison to GLH-60 for siRNA delivery. GLH-58/siRNA complexes demonstrated better efficiency in silencing the expression of the GFP gene in human breast cancer cells at concentrations of 5MUg/mL, well below the toxic dose. Moreover, delivery of multiple different siRNAs targeting the HIV genome demonstrated further inhibition of virus production. PMID- 26151707 TI - Metabolic syndrome, depression, anxiety and mortality. PMID- 26151708 TI - In-stent restenosis in a polytetrafluoroethylene covered stent combined with drug eluting stents: potential pathogenesis revealed by optical coherence tomography. PMID- 26151709 TI - Mobile mass lesion in the aorta after transcatheter aortic valve implantation: Thrombus or residue calcification. PMID- 26151710 TI - Disclosure of negative trial results. A call for action. PMID- 26151711 TI - Of hearts and minds: A case of simultaneous transient global amnesia and regional left ventricular dysfunction. PMID- 26151713 TI - Successful catheter ablation of idiopathic premature ventricular contractions originating from the "right" ventricular outflow tract in a patient with dextrocardia and situs inversus viscerum. PMID- 26151712 TI - An extensive discrepancy in myocardial uptake of thallium-201 and iodine-123 BMIPP in a patient with ST-segment elevation myocardial infarction treated using postconditioning with lactate-enriched blood. PMID- 26151714 TI - Response to Letter to the Editor. PMID- 26151715 TI - Assessment of aortic valve stenosis severity using intelligent phonocardiography. PMID- 26151716 TI - Elevated serum chloride is an independent risk factor for coronary heart disease: A retrospective study of more than 13,000 Han Chinese. PMID- 26151717 TI - 30-day mortality reduction with miniaturized extracorporeal circulation as compared to conventional cardiopulmonary bypass for coronary revascularization. Meta-analysis of randomized controlled trials. PMID- 26151718 TI - A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice. AB - BACKGROUND: Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, exercise intolerance and cardiac dysfunction. Unhealthy diet has been associated with increased risk of obesity and heart disease, but whether it directly affects cardiac function, and promotes the development and progression of HF is unknown. METHODS: We fed 8-week old male or female CD-1 mice with a standard diet (SD) or a diet rich in saturated fat and sugar, resembling a "Western" diet (WD). Cardiac systolic and diastolic function was measured at baseline and 4 and 8 weeks by Doppler echocardiography, and left ventricular (LV) end-diastolic pressure (EDP) by cardiac catheterization prior to sacrifice. An additional group of mice received WD for 4 weeks followed by SD (wash-out) for 8 weeks. RESULTS: WD-fed mice experienced a significant decreased in LV ejection fraction (LVEF), reflecting impaired systolic function, and a significant increase in isovolumetric relaxation time (IRT), myocardial performance index (MPI), and LVEDP, showing impaired diastolic function, without any sex-related differences. Switching to a SD after 4 weeks of WD partially reversed the cardiac systolic and diastolic dysfunction. CONCLUSIONS: A diet rich in saturated fat and sugars (WD) impairs cardiac systolic and diastolic function in the mouse. Further studies are required to define the mechanism through which diet affects cardiac function, and whether dietary interventions can be used in patients with, or at risk for, HF. PMID- 26151719 TI - Reactive Carbonyl Species Derived from Omega-3 and Omega-6 Fatty Acids. AB - Inflammation-related reactive oxygen species (ROS) and reactive nitrogen species (RNS) are associated with the development of cancer. ROS and RNS can directly damage biomacromolecules such as proteins, DNA, and lipids. Lipid peroxidation, however, can result in reactive carbonyl species (RCS) that can also modify proteins and DNA. In contrast to an extensive literature on the modification of proteins and DNA from omega-6 fatty acids, there are few studies on RCS generation from other fatty acids, particularly omega-3 fatty acids, which are frequently consumed from the diet and diet supplements. Therefore, a comparison between omega-3 and omega-6 fatty acids has been conducted. LC-MS/MS analysis of carbonyl-dinitrophenylhydrazine (DNPH) standards yielded characteristic fragment ions. Autoxidation products of alpha-linolenic acid and linoleic acid were then derivatized with DNPH and analyzed by LC-MS/MS. The results showed that alpha linolenic acid, an omega-3 fatty acid, generated more acrolein and crotonaldehyde than did linoleic acid, an omega-6 fatty acid. Omega-3 fatty acids might be easily degraded to smaller monoaldehydes or dicarbonyls. Omega-3 fatty acids have been considered as health improvement components for a long time. However, on the basis of the results presented here, use of omega-3 fatty acids should be re evaluated in vivo for safety purposes. PMID- 26151720 TI - Interfacial Morphology and Effects on Device Performance of Organic Bilayer Heterojunction Solar Cells. AB - The effects of interface roughness between donor and acceptor in a bilayer heterojunction solar cell were investigated on a polymer-polymer system based on poly(3-hexylthiophene) (P3HT) and poly(dioctylfluorene-alt-benzothiadiazole) (F8BT). Both polymers are known to reorganize into semicrystalline structures when heated above their glass-transition temperature. Here, the bilayers were thermally annealed below glass transition of the bulk polymers (~140 degrees C) at temperatures of 90, 100, and 110 degrees C for time periods from 2 min up to 250 min. No change of crystallinity could be observed at those temperatures. However, X-ray reflectivity and device characteristics reveal a coherent trend upon heat treatment. In X-ray reflectivity investigations, an increasing interface roughness between the two polymers is observed as a function of temperature and annealing time, up to a value of 1 nm. Simultaneously, according bilayer devices show an up to 80% increase of power conversion efficiency (PCE) for short annealing periods at any of the mentioned temperatures. Together, this is in agreement with the expectations for enlargement of the interfacial area. However, for longer annealing times, a decrease of PCE is observed, despite the ongoing increase of interface roughness. The onset of decreasing PCE shifts to shorter durations the higher the annealing temperature. Both, X-ray reflectivity and device characteristics display a significant change at temperatures below the glass transition temperatures of P3HT and F8BT. PMID- 26151722 TI - Microphase separation induced in the melt of Pluronic copolymers by blending with a hydrogen bonding urea-urethane end-capped supramolecular polymer. AB - Blending with a hydrogen-bonding supramolecular polymer is shown to be a successful novel strategy to induce microphase-separation in the melt of a Pluronic polyether block copolymer. The supramolecular polymer is a polybutadiene derivative with urea-urethane end caps. Microphase separation is analysed using small-angle X-ray scattering and its influence on the macroscopic rheological properties is analysed. FTIR spectroscopy provides a detailed picture of the inter-molecular interactions between the polymer chains that induces conformational changes leading to microphase separation. PMID- 26151723 TI - Combining Denitrifying Bacteria and Laser Spectroscopy for Isotopic Analyses (delta(15)N, delta(18)O) of Dissolved Nitrate. AB - We present a novel approach for nitrogen (delta(15)N) and oxygen (delta(18)O) isotopic analysis of nitrate in water based on the isotopic analysis of N2O produced from the conversion of NO3(-) by cultured denitrifying bacteria and off axis integrated cavity output spectroscopy (OA-ICOS). The headspace N2O was manually injected into an OA-ICOS isotopic N2O laser analyzer through a syringe septum port. Sample analysis time was ~300 s. The use of OA-ICOS technology yields accurate and precise delta(15)N and delta(18)O results for dissolved nitrate samples when nonlinearity issues are considered. This new isotope analytical technique thus improves the isotopic analysis of nitrates by (i) providing accurate measurements of delta(15)N and delta(18)O without preconcentration, (ii) eliminating interferences by other gas substances (i.e., H2O and CO2), and (iii) reducing extensive maintenance and costs of isotope ratio mass spectrometers (IRMS). This approach will greatly streamline the identification and quantification of nitrate sources in aquatic systems. PMID- 26151725 TI - Perceptions of body weight and nutritional practices among male and female National Collegiate Athletic Association Division II athletes. AB - OBJECTIVE: This study investigated body weight and nutritional behavior perceptions among Division II collegiate athletes. PARTICIPANTS: The sample was composed of 155 collegiate athletes who responded to a survey. METHODS: Data were self-reported by athletes via questionnaire. Independent-sample t tests were used to identify significant gender differences related to body weight perceptions, nutritional practices, and ideal weight difference (IWD). An alpha level of .05 was used to determine statistical significance. RESULTS: Mean +/- SD female and male IWD was -6.8 +/- 8.8 and 1.3 +/- 12.3 lbs, respectively (p < .001). Significant differences in level of agreement regarding perceived body weight effects on performance and dietary practices existed between genders. CONCLUSIONS: Significant gender differences may exist regarding body weight perceptions and nutritional practices among collegiate athletes. Deliverance of gender-specific educational information about proper nutritional practices is warranted. To properly tailor interventions to specific sports, research with larger sample sizes is needed. PMID- 26151724 TI - Localized translation near the mitochondrial outer membrane: An update. AB - Local synthesis of proteins near their activity site has been demonstrated in many biological systems, and has diverse contributions to cellular functions. Studies in recent years have revealed that hundreds of mitochondria-destined proteins are synthesized by cytosolic ribosomes near the mitochondrial outer membrane, indicating that localized translation also occurs at this cellular locus. Furthermore, in the last year central factors that are involved in this process were identified in yeast, Drosophila, and human cells. Herein we review the experimental evidence for localized translation on the cytosolic side of the mitochondrial outer membrane; in addition, we describe the factors that are involved in this process and discuss the conservation of this mechanism among various species. We also describe the relationship between localized translation and import into the mitochondria and suggest avenues of study that look beyond cotranslational import. Finally we discuss future challenges in characterizing the mechanisms for localized translation and its physiological significance. PMID- 26151726 TI - Scattering Function for Branched Wormlike Chains. AB - Wormlike or threadlike structures with local cylindrical geometry are abundantly found in nature and technical products. A thorough structural characterization in the bulk for a whole ensemble, however, is difficult. The inherent semiordered nature of the tortuous large-scale structure and especially the quantification of branching renders an assessment difficult. In the present work we introduce a hybrid function expressing the scattering intensities for X-rays, neutrons, or light in the small-angle regime for this system. The function is termed "hybrid" because it employs terms from different approaches. The large-scale structure is described via a Guinier term as well as a concomitant power-law expression in momentum transfer q taken from the so-called unified function. The local cylindrical shape, however, is taken into account through a form factor for cylinders from rigid-body modeling. In principle, the latter form factor can be replaced by an expression for any other regular body so that the new hybrid function is a versatile tool for studying hierarchical structures assembled from uniform subunits. The appropriateness and capability of the new function for cylindrical structures is exemplified using the example of a wormlike micellar system. PMID- 26151727 TI - Rhodium(ii) dimers without metal-metal bonds. AB - Oxidation of ((Me)BDI)Rh(cyclooctene) ((Me)BDI = [2,6-Me(2)C(6)H(3)NCMe](2)CH) with Br(2) or I(2) produces paramagnetic halide-bridged Rh(II) dimers [((Me)BDI)Rh](2)(MU-X)(2) without a direct Rh-Rh bond. Steric factors are proposed to play a key role in preventing the formation of Rh-Rh bonded alternative structures. PMID- 26151728 TI - Analyte-Size-Dependent Ionization and Quantification of Monosaccharides in Human Plasma Using Cation-Exchanged Smectite Layers. AB - Smectite, a synthetic inorganic polymer with a saponite structure, was subjected to matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Typical organic matrix molecules 2,4,6-trihydroxyacetophenone (THAP) and 2,5 dihydroxybenzoic acid (DHBA) were intercalated into the layer spacing of cation exchanged smectite, and the complex was used as a new matrix for laser desorption/ionization mass spectrometry. Because of layer spacing limitations, only a small analyte that could enter the layer and bind to THAP or DHBA could be ionized. This was confirmed by examining different analyte/matrix preparation methods and by measuring saccharides with different molecular sizes. Because of the homogeneous distribution of THAP molecules in the smectite layer spacing, high reproducibility of the analyte peak intensity was achieved. By using isotope labeled (13)C6-d-glucose as the internal standard, quantitative analysis of monosaccharides in pretreated human plasma sample was performed, and the value of 8.6 +/- 0.3 MUg/mg was estimated. PMID- 26151729 TI - A Family of Highly Efficient CuI-Based Lighting Phosphors Prepared by a Systematic, Bottom-up Synthetic Approach. AB - Copper(I) iodide (CuI)-based inorganic-organic hybrid materials in the general chemical formula of CuI(L) are well-known for their structural diversity and strong photoluminescence and are therefore considered promising candidates for a number of optical applications. In this work, we demonstrate a systematic, bottom up precursor approach to developing a series of CuI(L) network structures built on CuI rhomboid dimers. These compounds combine strong luminescence due to the CuI inorganic modules and significantly enhanced thermal stability as a result of connecting individual building units into robust, extended networks. Examination of their optical properties reveals that these materials not only exhibit exceptionally high photoluminescence performance (with internal quantum yield up to 95%) but also that their emission energy and color are systematically tunable through modification of the organic component. Results from density functional theory calculations provide convincing correlations between these materials' crystal structures and chemical compositions and their optophysical properties. The advantages of cost-effective, solution-processable, easily scalable and fully controllable synthesis as well as high quantum efficiency with improved thermal stability, make this phosphor family a promising candidate for alternative, RE free phosphors in general lighting and illumination. This solution-based precursor approach creates a new blueprint for the rational design and controlled synthesis of inorganic-organic hybrid materials. PMID- 26151730 TI - Evolution of the Millon Clinical Multiaxial Inventory. AB - Dr. Theodore Millon (1928-2014) was a primary architect for the personality disorders in the DSM-III, a structure that has endured into the DSM-5. His 1969 book, Modern Psychopathology, created an elegant framework into which the well known personality prototypes could be fitted and understood. His theoretical work soon led into the creation of several psychological inventories, most notably the Millon Clinical Multiaxial Inventory (MCMI). The MCMI, now in preparation for its 4th major edition, has been a very popular instrument among clinicians. This article explores the history of the MCMI's development from its origins, through 2 distinct theoretical phases, and to its current status as the MCMI-IV is finalized. PMID- 26151731 TI - Laser-driven electron dynamics for circular dichroism in mass spectrometry: from one-photon excitations to multiphoton ionization. AB - The distinction of enantiomers is a key aspect of chemical analysis. In mass spectrometry the distinction of enantiomers has been achieved by ionizing the sample with circularly polarized laser pulses and comparing the ion yields for light of opposite handedness. While resonant excitation conditions are expected to be most efficient, they are not required for the detection of a circular dichroism (CD) in the ion yield. However, the prediction of the size and sign of the circular dichroism becomes challenging if non-resonant multiphoton excitations are used to ionize the sample. Employing femtosecond laser pulses to drive electron wavepacket dynamics based on ab initio calculations, we attempt to reveal underlying mechanisms that determine the CD under non-resonant excitation conditions. Simulations were done for (R)-1,2-propylene oxide, using time dependent configuration interaction singles with perturbative doubles (TD-CIS(D)) and the aug-cc-pVTZ basis set. Interactions between the electric field and the electric dipole and quadrupole as well as between the magnetic field and the magnetic dipole were explicitly accounted for. The ion yield was determined by treating states above the ionization potential as either stationary or non stationary with energy-dependent lifetimes based on an approved heuristic approach. The observed population dynamics do not allow for a simple interpretation, because of highly non-linear interactions. Still, the various transition pathways are governed by resonant enantiospecific n-photon excitation, with preferably high transition dipole moments, which eventually dominate the CD in the ionized population. PMID- 26151732 TI - (F)Utility of invasive haemodynamic measurements to guide percutaneous intervention in chronic coronary artery disease. AB - Percutaneous coronary intervention (PCI) in chronic stable coronary artery disease has not been shown to reduce the incidence of myocardial infarction or death. There is, however, evidence that the outcome from PCI is dependent on the amount of myocardial ischaemia. This review provides an overview of coronary circulatory pathophysiology and focuses on fractional flow reserve from a semantical, conceptual and practical point of view. PMID- 26151733 TI - Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells. AB - Hepatocellular carcinoma (HCC) is an aggressive form of cancer, with high rates of morbidity and mortality, a poor prognosis and limited therapeutic options. The objective of the present study was to demonstrate the anticancer activity of oleanolic acid in HepG2 human HCC cells. Cell viability was evaluated using an MTT assay, following administration of various doses of oleanolic acid. The effect of oleanolic acid on cell cycle phase distribution and mitochondrial membrane potential was evaluated using flow cytometry with propidium iodide and rhodamine-123 DNA-binding cationic fluorescent dyes. Fluorescence microscopy was employed to detect morphological changes in HepG2 cells following oleanolic acid treatment. The results revealed that oleanolic acid induced a dose-dependent, as well as time-dependent inhibition in the growth of HepG2 cancer cells. Following acridine orange and ethidium bromide staining, treatment with various doses (0, 5, 25 and 50 uM) of oleanolic acid induced typical morphological changes associated with apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and apoptotic body formation. Cell cycle analysis revealed that oleanolic acid induced cell cycle arrest in HepG2 cells at the sub-G1 (apoptotic) phase of the cell cycle, in a dose-dependent manner. Staining with Annexin V fluorescein isothiocyanate and propidium iodide revealed that apoptosis occurred early in these cells. Oleanolic acid treatment also resulted in fragmentation of nuclear DNA in a dose-dependent manner, producing the typical features of DNA laddering on an agarose gel. The results also demonstrated that oleanolic acid treatment resulted in a potent loss of mitochondrial membrane potential, which also occurred in a dose-dependent manner. Therefore, oleanolic acid may be used as a therapeutic agent in the treatment of human HCC. PMID- 26151735 TI - Editorial Retraction. PMID- 26151734 TI - Effect of Sesamin Supplementation on Cardiovascular Risk Factors in Women with Rheumatoid Arthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory disease with increased mortality from cardiovascular disease (CVD). Oxidative stress has a critical role in the pathogenesis of RA and CVD. Sesamin, the main lignin constituent of sesame, has several antioxidant and anti-inflammatory effects. This study aimed to investigate the effects of sesamin supplementation on anthropometric indices, lipid profile, blood pressure, and oxidative stress markers in women with RA. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 44 patients with RA were randomly divided into 2 groups (intervention and control). Patients consumed 200 mg/day sesamin supplement and placebo in the intervention and control groups, respectively, for 6 weeks (spring 2014). At baseline and at the end of the study, anthropometric indices and blood pressure were assessed. Serum concentrations of lipid profile, malondialdehyde (MDA), and total antioxidant capacity (TAC) were also determined. RESULTS: At the end of study, sesamin supplementation significantly decreased serum levels of MDA (p = 0.018) and increased TAC and high-density lipoprotein cholesterol (HDL-C) levels in patients with RA (p = 0.020 and p = 0.007, respectively). In the sesamin group, the mean of weight, body mass index, waist-to-hip ratio, body fat, systolic blood pressure, and the concentration of other lipid profiles (triglycerides, total cholesterol, and low-density lipoprotein cholesterol [LDL-C]) were also significantly decreased at the end of study compared to baseline values (p < 0.05). However, the difference between the 2 groups was not statistically significant in this regard (p > 0.05). CONCLUSION: Sesamin exhibited a protective effect on cardiovascular risk factors in patients with RA. However, further investigation is suggested. PMID- 26151736 TI - Agrobacterium tumefaciens Gene Transfer: How a Plant Pathogen Hacks the Nuclei of Plant and Nonplant Organisms. AB - Agrobacterium species are soilborne gram-negative bacteria exhibiting predominantly a saprophytic lifestyle. Only a few of these species are capable of parasitic growth on plants, causing either hairy root or crown gall diseases. The core of the infection strategy of pathogenic Agrobacteria is a genetic transformation of the host cell, via stable integration into the host genome of a DNA fragment called T-DNA. This genetic transformation results in oncogenic reprogramming of the host to the benefit of the pathogen. This unique ability of interkingdom DNA transfer was largely used as a tool for genetic engineering. Thus, the artificial host range of Agrobacterium is continuously expanding and includes plant and nonplant organisms. The increasing availability of genomic tools encouraged genome-wide surveys of T-DNA tagged libraries, and the pattern of T-DNA integration in eukaryotic genomes was studied. Therefore, data have been collected in numerous laboratories to attain a better understanding of T-DNA integration mechanisms and potential biases. This review focuses on the intranuclear mechanisms necessary for proper targeting and stable expression of Agrobacterium oncogenic T-DNA in the host cell. More specifically, the role of genome features and the putative involvement of host's transcriptional machinery in relation to the T-DNA integration and effects on gene expression are discussed. Also, the mechanisms underlying T-DNA integration into specific genome compartments is reviewed, and a theoretical model for T-DNA intranuclear targeting is presented. PMID- 26151737 TI - Aggregates of the pentacenequinone derivative as reactors for the preparation of Ag@Cu2O core-shell NPs: an active photocatalyst for Suzuki and Suzuki type coupling reactions. AB - Aggregates of the pentacenequinone derivative 1 act as reactors and stabilizers for rapid and facile preparation of Ag@Cu2O core-shell nanoparticles (NPs) in aqueous medium. The in situ generated Ag@Cu2O core-shell hybrid materials enabled efficient visible light harvesting to catalyse the palladium free Suzuki-Miyaura and Suzuki type cross coupling reactions at room temperature. PMID- 26151738 TI - Early Morning Functioning in Stimulant-Treated Children and Adolescents with Attention-Deficit/Hyperactivity Disorder, and its Impact on Caregivers. AB - OBJECTIVE: The purpose of this study was to examine the temporal occurrence and severity of inadequate attention-deficit/hyperactivity disorder (ADHD) symptom control throughout the day, and, more specifically, the frequency and severity of associated functional impairments and their apparent emotional impact on parents and caregivers during the early morning routine before school, in children and adolescents with ADHD currently treated with stable doses of stimulant medications. METHODS: Information was obtained from 201 primary caregivers of children and adolescents with ADHD using a self-administered, on-line quantitative research survey. RESULTS: Inadequately controlled ADHD symptoms were rated as most severe during the evening homework time and the early morning routine. The majority of caregivers reported early morning ADHD symptoms and impairment of early morning functioning (EMF) as moderate to severe. Caregiver reactions to their child's early morning ADHD symptoms and unwanted behaviors included feeling overwhelmed, exhausted, and constantly stressed. CONCLUSIONS: Control of EMF impairments from inadequately controlled ADHD symptoms is a significant unmet need in children and adolescents with ADHD treated with stable morning doses of stimulant medications. Current orally administered stimulant treatment options have not addressed this challenge. PMID- 26151739 TI - There and back again: The journey of the estrogen-related receptors in the cancer realm. AB - The identification of two genes encoding polypeptides with structural features common with the estrogen receptor more than a quarter century ago, referred to as the estrogen-related receptors (ERRs), subsequently led to the discovery of several previously unrecognized hormone responsive systems through the application of reverse endocrinology. Paradoxically, the natural ligand(s) associated with members of the ERR subfamily remains to be identified. While initial studies on the mode of action and physiological functions of the ERRs focused on interaction with estrogen signalling in breast cancer, subsequent work showed that the ERRs are ubiquitous master regulators of cellular energy metabolism. This review aims to demonstrate that the ERRs occupy a central node at the interface of cancer and metabolism, and that modulation of their activity may represent a worthwhile strategy to induce metabolic vulnerability in tumors of various origins and thus achieve a more comprehensive response to current therapies. PMID- 26151741 TI - Steroid modulation of neurogenesis: Focus on radial glial cells in zebrafish. AB - Estrogens are known as steroid hormones affecting the brain in many different ways and a wealth of data now document effects on neurogenesis. Estrogens are provided by the periphery but can also be locally produced within the brain itself due to local aromatization of circulating androgens. Adult neurogenesis is described in all vertebrate species examined so far, but comparative investigations have brought to light differences between vertebrate groups. In teleost fishes, the neurogenic activity is spectacular and adult stem cells maintain their mitogenic activity in many proliferative areas within the brain. Fish are also quite unique because brain aromatase expression is limited to radial glia cells, the progenitor cells of adult fish brain. The zebrafish has emerged as an interesting vertebrate model to elucidate the cellular and molecular mechanisms of adult neurogenesis, and notably its modulation by steroids. The main objective of this review is to summarize data related to the functional link between estrogens production in the brain and neurogenesis in fish. First, we will demonstrate that the brain of zebrafish is an endogenous source of steroids and is directly targeted by local and/or peripheral steroids. Then, we will present data demonstrating the progenitor nature of radial glial cells in the brain of adult fish. Next, we will emphasize the role of estrogens in constitutive neurogenesis and its potential contribution to the regenerative neurogenesis. Finally, the negative impacts on neurogenesis of synthetic hormones used in contraceptive pills production and released in the aquatic environment will be discussed. PMID- 26151742 TI - Incidence rate of type 2 diabetes is >50% lower in GrassrootsHealth cohort with median serum 25-hydroxyvitamin D of 41 ng/ml than in NHANES cohort with median of 22 ng/ml. AB - Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged >=20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the GrassrootsHealth (GRH) cohort was 41 ng/ml (N=4933) while in the 2005-6 National Health and Nutrition Examination Survey (NHANES) it was 22 ng/ml (N=4078) (P<0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval=1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval=6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17-24 ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P=0.02 and 4.8, P=0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population. PMID- 26151740 TI - Steroid receptor coactivators as therapeutic targets in the female reproductive system. AB - The steroid receptor coactivators (SRCs/p160/NCOA) are a family of three transcriptional coregulators initially discovered to transactivate the transcriptional potency of steroid hormone receptors. Even though SRCs were also found to modulate the activity of multiple other transcription factors, their function is still strongly associated with regulation of steroid hormone action and many studies have found that they are critical for the regulation of reproductive biology. In the case of the female reproductive tract, SRCs have been found to play crucial roles in its physiology, ranging from ovulation, implantation, to parturition. Not surprisingly, SRCs' action has been linked to numerous abnormalities and debilitating disorders of female reproductive tissues, including infertility, cancer, and endometriosis. Many of these pathologies are still in critical need of therapeutic intervention and "proof-of-principle" studies have found that SRCs are excellent targets in pathological states. Therefore, small molecule modulators of SRCs' activity could be applied in the future in the treatment of many diseases of the female reproductive system. PMID- 26151744 TI - Corrigendum to "Target-specific near-IR induced drug release and photothermal therapy with accumulated Au/Ag hollow nanoshells on pulmonary cancer cell membranes" [Biomaterials 45 (2015) 81-92]. PMID- 26151743 TI - Characterization of Oct4-GFP transgenic mice as a model to study the effect of environmental estrogens on the maturation of male germ cells by using flow cytometry. AB - Oct4 is involved in regulation of pluripotency during normal development and is down-regulated during formation of postnatal reservoir of germ cells. We propose thatOct4/GFP transgenic mouse, which mimics the endogenous expression pattern of Oct4, could be used as a mammalian model to study the effects of environmental estrogens on the development of male germ cells. Oct4/GFP maturation profile was assessed during postnatal days -PND- 3, 5, 7, 10, 14 and 80, using flow cytometry. Then, we exposed pregnant mothers to 17alpha-ethinylestradiol (EE2) from day post coitum (dpc) 5 to PND7. Percentage of Oct4/GFP-expressing cells and levels of expression of Oct4/GPF were increased in PND7 after EE2 exposure. These observations were confirmed by analysis of GFP and endogenous Oct4 protein in the seminiferous tubules and by a reduction in epididymal sperm count in adult mice. We introduced Oct4/GFP mouse together with flow cytometry as a tool to evaluate changes in male germ cells development. PMID- 26151746 TI - Charge optimized many-body (COMB) potential for Al2O3 materials, interfaces, and nanostructures. AB - This work presents the development and applications of a new empirical, variable charge potential for Al2O3 systems within the charge optimized many-body (COMB) potential framework. The potential can describe the fundamental physical properties of Al2O3, including cohesive energy, elastic constants, defect formation energies, surface energies and phonon properties of alpha-Al2O3 comparable to that obtained from experiments and first-principles calculations. The potential is further employed in classical molecular dynamics (MD) simulations to validate and predict the properties of the Al (1 1 1)-Al2O3 (0 0 0 1) interface, tensile properties of Al nanowires, Al2O3 nanowires, Al2O3-covered Al nanowires, and defective Al2O3 nanowires. The results demonstrate that the potential is well-suited to model heterogeneous material systems involving Al and Al2O3. Most importantly, the parameters can be seamlessly coupled with COMB3 parameters for other materials to enable MD simulations of a wide range of heterogeneous material systems. PMID- 26151745 TI - An injectable elastin-based gene delivery platform for dose-dependent modulation of angiogenesis and inflammation for critical limb ischemia. AB - Critical limb ischemia is a major clinical problem. Despite rigorous treatment regimes, there has been only modest success in reducing the rate of amputations in affected patients. Reduced level of blood flow and enhanced inflammation are the two major pathophysiological changes that occur in the ischemic tissue. The objective of this study was to develop a controlled dual gene delivery system capable of delivering therapeutic plasmid eNOS and IL-10 in a temporal manner. In order to deliver multiple therapeutic genes, an elastin-like polypeptide (ELP) based injectable system was designed. The injectable system was comprised of hollow spheres and an in situ-forming gel scaffold of elastin-like polypeptide capable of carrying gene complexes, with an extended manner release profile. In addition, the ELP based injectable system was used to deliver human eNOS and IL 10 therapeutic genes in vivo. A subcutaneous dose response study showed enhanced blood vessel density in the treatment groups of eNOS (20 MUg) and IL-10 (10 MUg)/eNOS (20 MUg) and reduced inflammation with IL-10 (10 MUg) alone. Next, we carried out a hind-limb ischemia model comparing the efficacy of the following interventions; Saline; IL-10, eNOS and IL-10/eNOS. The selected dose of eNOS, exhibited enhanced angiogenesis. IL-10 treatment groups showed reduction in the level of inflammatory cells. Furthermore, we demonstrated that eNOS up-regulated major proangiogenic growth factors such as vascular endothelial growth factors, platelet derived growth factor B, and fibroblast growth factor 1, which may explain the mechanism of this approach. These factors help in formation of a stable vascular network. Thus, ELP injectable system mediating non-viral delivery of human IL10-eNOS is a promising therapy towards treating limb ischemia. PMID- 26151747 TI - Inhibition of Gastric Tumor Cell Growth Using Seed-targeting LNA as Specific, Long-lasting MicroRNA Inhibitors. AB - MicroRNAs regulate eukaryotic gene expression upon pairing onto target mRNAs. This targeting is influenced by the complementarity between the microRNA "seed" sequence at its 5' end and the seed-matching sequences in the mRNA. Here, we assess the efficiency and specificity of 8-mer locked nucleic acid (LNA)-modified oligonucleotides raised against the seeds of miR-372 and miR-373, two embryonic stem cell-specific microRNAs prominently expressed in the human gastric adenocarcinoma AGS cell line. Provided that the pairing is perfect over all the eight nucleotides of the seed and starts at nucleotide 2 or 1 at the microRNA 5' end, these short LNAs inhibit miR-372/373 functions and derepress their common target, the cell cycle regulator LATS2. They decrease cell proliferation in vitro upon either transfection at nanomolar concentrations or unassisted delivery at micromolar concentrations. Subcutaneously delivered LNAs reduce tumor growth of AGS xenografts in mice, upon formation of a stable, specific heteroduplex with the targeted miR-372 and -373 and LATS2 upregulation. Their therapeutic potential is confirmed in fast-growing, miR-372-positive, primary human gastric adenocarcinoma xenografts in mice. Thus, microRNA silencing by 8-mer seed targeting LNAs appears a valuable approach for both loss-of-function studies aimed at elucidating microRNA functions and for microRNA-based therapeutic strategies. PMID- 26151748 TI - Reorganization of Motor Execution Networks During Sub-Acute Phase After Stroke. AB - Numerous studies focused on brain reorganization after stroke from aspects of task-related brain activity and resting-state brain networks. However, studies focusing on the longitudinal reorganization of task-state brain networks were scarce. In this study, functional magnetic resonance imaging data were collected from twelve stroke patients during blocked finger-tapping task at four post stroke time points (less than 10 days, around 2 weeks, 1 month and 3 months), respectively. The dynamic changes and prognostic value of the network parameters (i.e., topological parameters, functional connectivity and nodal parameters) in task-state motor execution networks were thoroughly evaluated. We found that the topological configuration (clustering coefficient and characteristic path length) of task-state motor execution networks underwent significant shift during stroke recovery. Especially, we found the topological configuration of task-state motor execution networks at the early recovery stage were capable of predicting the motor function restoration during sub-acute phase. In addition, we found increasing functional connectivity between ipsilesional cerebellum and motor cortices in task-state motor execution networks. In general, this study demonstrated the reorganization and prognostic value of task-state brain network after stroke, which provides new insights into understanding the brain reorganization and rehabilitation after stroke. PMID- 26151749 TI - The Immune Interplay between Thyroid Papillary Carcinoma and Hepatic Fibrosis. AB - BACKGROUND: A high prevalence of thyroid papillary cancer was reported in hepatitis-C-virus (HCV) positive patients. However, the mechanistic role of hepatic-fibrosis in thyroid malignancy progressions is still unclear. AIM: We aimed to study the immune-modulatory interactions between thyroid papillary carcinoma and hepatic-fibrosis. METHODS: Hepatic-fibrosis was induced in nude-nu male mice by intra-peritoneal administration of carbon-tetrachloride. To induce thyroid-tumor, a thyroid papillary carcinoma cell line (NPA) was injected subcutaneously in the backs. Fibrotic profile was estimated by alpha-smooth muscle-actin (alphaSMA) expression in liver tissue extracts using western-blots and RT-PCR. Intra-hepatic NK cells were isolated and stained for NK activity (CD107a) by flow cytometry. Liver histopathology (H&E staining), thyroid tumor mass and serum alanine aminotransferase (ALT), serum vascular endothelial growth factor (VEGF) and free-T4 levels were also assessed. RESULTS: Ex-vivo: NPA cells were co-cultured with intra-hepatic NK cells isolated from fibrotic mice with/without the tumor were analyzed for CFSE-proliferations. Both tumor groups (with/without hepatic-fibrosis) excreted higher serum free T4 levels. Hepatic fibrosis increased tumor weight and size and serum free-T4 levels. In addition, tumor induction increased liver injury (both hepatic-fibrosis, necro-inflammation and serum ALT levels). In addition, tumor-bearing animals with hepatic-fibrosis had increased NK activity. NPA tumor-bearing animals increased fibrosis in spite of increased NK activity; probably due to a direct effect through increased serum free-T4 excretions. Serum VEGF levels were significantly increased in the fibrotic- bearing tumor groups compared to the non-fibrotic groups. In-vitro, NK cells from fibrotic tumor-bearing animals reduced proliferation of NPA cells. This decrease is attributed to increase NK cells activity in the fibrotic animals with the NPA tumors. CONCLUSIONS: Our results propose that NK cells although were stimulated in advanced fibrosis with tumor, they lost their anti-tumor and anti fibrotic activity probably due to secretions of T4 and VEFG and may explain increased risk of thyroid tumors in chronic HCV patients. PMID- 26151750 TI - Spatial and Temporal Characteristics of Pastoral Mobility in the Far North Region, Cameroon: Data Analysis and Modeling. AB - Modeling the movements of humans and animals is critical to understanding the transmission of infectious diseases in complex social and ecological systems. In this paper, we focus on the movements of pastoralists in the Far North Region of Cameroon, who follow an annual transhumance by moving between rainy and dry season pastures. Describing, summarizing, and modeling the transhumance movements in the region are important steps for understanding the role these movements may play in the transmission of infectious diseases affecting humans and animals. We collected data on this transhumance system for four years using a combination of surveys and GPS mapping. An analysis on the spatial and temporal characteristics of pastoral mobility suggests four transhumance modes, each with its own properties. Modes M1 and M2 represent the type of transhumance movements where pastoralists settle in a campsite for a relatively long period of time (>=20 days) and then move around the area without specific directions within a seasonal grazing area. Modes M3 and M4 on the other hand are the situations when pastoralists stay in a campsite for a relatively short period of time (<20 days) when moving between seasonal grazing areas. These four modes are used to develop a spatial-temporal mobility (STM) model that can be used to estimate the probability of a mobile pastoralist residing at a location at any time. We compare the STM model with two reference models and the experiments suggest that the STM model can effectively capture and predict the space-time dynamics of pastoral mobility in our study area. PMID- 26151751 TI - Aspirin for Primary Prevention of Cardiovascular Disease and Cancer. A Benefit and Harm Analysis. AB - BACKGROUND: Aspirin is widely used for prevention of cardiovascular disease. In recent years randomized trials also suggested a preventive effect for various types of cancer. We aimed to assess, in a quantitative way, benefits and harms of aspirin for primary prevention of both cardiovascular disease and cancer for a general US population between 40 and 85 years of age. METHODS: We used the Gail/National Cancer Institute approach for assessing benefits and harms. This approach provides a probability that a treatment is more beneficial than harmful and incorporates multiple outcomes, the importance of these outcomes, considers different outcome risks and treats mortality as a competing risk. Our main outcomes were the risks of seven types of cancer, myocardial infarction, ischemic and hemorrhagic stroke and gastrointestinal bleeding. We obtained effect estimates from recent meta-analyses of randomized trials and used baseline risks from the Centers for Disease Control. We conducted four sensitivity analyses to assess the influence of different assumptions about outcome risks and preferences and considered the sampling variation of the effect estimates for aspirin. RESULTS: The main analysis as well as the sensitivity analyses showed that aspirin has more benefits than harms. In the main analysis, the index (positive if number of prevented events > excess number of harm events over 10 years per 1,000 persons) ranged from 2 (95% CI 0.0 to 11.8; in women age 45 to 54 years) to 8 (95% CI -0.1 to 83.7; in men age 65 to 74 years). In the sensitivity analyses, the index was also positive for all age categories suggesting more benefits than harms. CONCLUSION: This study suggests an overall benefit of aspirin for primary prevention of cardiovascular disease and cancer based on population-based data. For individual preventive counseling, additional benefit harm analyses should explore which individuals should or should not take aspirin based on their risk profile for cardiovascular, cancer and gastrointestinal outcomes and based on their outcome preferences. Thereby, risk-stratified and preference-sensitive prevention could become a reality. PMID- 26151752 TI - Trends in Prevalence of HIV-1 Drug Resistance in a Public Clinic in Maputo, Mozambique. AB - BACKGROUND: An observational study was conducted in Maputo, Mozambique, to investigate trends in prevalence of HIV drug resistance (HIVDR) in antiretroviral (ART) naive subjects initiating highly active antiretroviral treatment (HAART). METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the pattern of drug resistance mutations (DRMs) found in adults on ART failing first-line HAART [patients with detectable viral load (VL)]. Untreated subjects [Group 1 (G1; n=99)] and 274 treated subjects with variable length of exposure to ARV's [6-12 months, Group 2 (G2;n=93); 12-24 months, Group 3 (G3;n=81); >24 months (G4;n=100)] were enrolled. Virological and immunological failure (VF and IF) were measured based on viral load (VL) and T lymphocyte CD4+ cells (TCD4+) count and genotypic resistance was also performed. Major subtype found was C (untreated: n=66, 97,06%; treated: n=36, 91.7%). Maximum virological suppression was observed in G3, and significant differences intragroup were observed between VF and IF in G4 (p=0.022). Intergroup differences were observed between G3 and G4 for VF (p=0.023) and IF between G2 and G4 (p=0.0018). Viral suppression (<50 copies/ml) ranged from 84.9% to 90.1%, and concordant VL and DRM ranged from 25% to 57%. WHO cut-off for determining VF as given by 2010 guidelines (>5000 copies/ml) identified 50% of subjects carrying DRM compared to 100% when lower VL cut-off was used (<50 copies/ml). Length of exposure to ARVs was directly proportional to the complexity of DRM patterns. In Mozambique, VL suppression was achieved in 76% of individuals after 24 months on HAART. This is in agreement with WHO target for HIVDR prevention target (70%). CONCLUSIONS: We demonstrated that the best way to determine therapeutic failure is VL compared to CD4 counts. The rationalized use of VL testing is needed to ensure timely detection of treatment failures preventing the occurrence of TDR and new infections. PMID- 26151753 TI - Effects of Statins on Renal Outcome in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis. AB - BACKGROUND: HMG CoA reductase inhibitors (statins) are known to prevent cardiovascular disease and improve lipid profiles. However, the effects of statins on renal outcomes, including decline in estimated glomerular filtration rate (eGFR) and proteinuria in patients with chronic kidney disease (CKD), are controversial. This meta-analysis evaluated the impact of statins on renal outcomes in patients with CKD. MATERIALS AND METHODS: We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane Databases. The inclusion criteria were published RCT and cohort studies comparing statin therapy to placebo or active controls in patients with CKD (eGFR <60 ml/min/1.73 m(2)) not requiring dialysis. The primary outcome was the differences in the change of eGFR. We also examined change of protein concentration in urine as a secondary outcome. A meta analysis comparing statin and its control groups and a subgroup analysis examining intensity of statin were performed. RESULTS: From 142 full-text articles, 10 studies were included in the meta-analysis. Overall, there was a significant difference in rate of eGFR change per year favoring statin group (mean difference (MD) = 0.10 ml/min/1.73 m(2), 95% CI: 0.09 to 0.12). In our subgroup analysis, those who received high-intensity statins had a significant difference in eGFR with a MD of 3.35 (95% CI: 0.91 to 5.79) ml/min/1.73 m(2) compared to control. No significant change in eGFR was found with moderate- and low-intensity statin therapy. Compared with the control group, the statin group did not have a difference in reduction of proteinuria with MD in change of proteinuria of 0.19 gm/day (95% CI: -0.02 to 0.40). CONCLUSION: Overall, there was a difference in change of eGFR between the statin and control group. High intensity statins were found to improve a decline in eGFR in population with CKD not requiring dialysis compared with control, but moderate- and low-intensity statins were not. Statins were not found to decrease proteinuria in patients with CKD. PMID- 26151755 TI - Does Early Psychological Intervention Promote Recovery From Posttraumatic Stress? AB - In the wake of the terrorist attacks at the World Trade Center, more than 9,000 counselors went to New York City to offer aid to rescue workers, families, and direct victims of the violence of September 11, 2001. These mental health professionals assumed that many New Yorkers were at high risk for developing posttraumatic stress disorder (PTSD), and they hoped that their interventions would mitigate psychological distress and prevent the emergence of this syndrome. Typically developing in response to horrific, life-threatening events, such as combat, rape, and earthquakes, PTSD is characterized by reexperiencing symptoms (e.g., intrusive recollections of the trauma, nightmares), emotional numbing and avoidance of reminders of the trauma, and hyperarousal (e.g., exaggerated startle, difficulty sleeping). People vary widely in their vulnerability for developing PTSD in the wake of trauma. For example, higher cognitive ability and strong social support buffer people against PTSD, whereas a family or personal history of emotional disorder heightens risk, as does negative appraisal of one's stress reactions (e.g., as a sign of personal weakness) and dissociation during the trauma (e.g., feeling unreal or experiencing time slowing down). However, the vast majority of trauma survivors recover from initial posttrauma reactions without professional help. Accordingly, the efficacy of interventions designed to mitigate acute distress and prevent long-term psychopathology, such as PTSD, needs to be evaluated against the effects of natural recovery. The need for controlled evaluations of early interventions has only recently been widely acknowledged. Psychological debriefing-the most widely used method-has undergone increasing empirical scrutiny, and the results have been disappointing. Although the majority of debriefed survivors describe the experience as helpful, there is no convincing evidence that debriefing reduces the incidence of PTSD, and some controlled studies suggest that it may impede natural recovery from trauma. Most studies show that individuals who receive debriefing fare no better than those who do not receive debriefing. Methodological limitations have complicated interpretation of the data, and an intense controversy has developed regarding how best to help people in the immediate wake of trauma. Recent published recommendations suggest that individuals providing crisis intervention in the immediate aftermath of the event should carefully assess trauma survivors' needs and offer support as necessary, without forcing survivors to disclose their personal thoughts and feelings about the event. Providing information about the trauma and its consequences is also important. However, research evaluating the efficacy of such "psychological first aid" is needed. Some researchers have developed early interventions to treat individuals who are already showing marked stress symptoms, and have tested methods of identifying those at risk for chronic PTSD. The single most important indicator of subsequent risk for chronic PTSD appears to be the severity or number of posttrauma symptoms from about 1 to 2 weeks after the event onward (provided that the event is over and that there is no ongoing threat). Cognitive-behavioral treatments differ from crisis intervention (e.g., debriefing) in that they are delivered weeks or months after the trauma, and therefore constitute a form of psychotherapy, not immediate emotional first aid. Several controlled trials suggest that certain cognitive behavioral therapy methods may reduce the incidence of PTSD among people exposed to traumatic events. These methods are more effective than either supportive counseling or no intervention. In this monograph, we review risk factors for PTSD, research on psychological debriefing, recent recommendations for crisis intervention and the identification of individuals at risk of chronic PTSD, and research on early interventions based on cognitive-behavioral therapy. We close by placing the controversy regarding early aid for trauma survivors in its social, political, and economic context. PMID- 26151754 TI - Differences in the Pattern of Hemodynamic Response to Self-Face and Stranger-Face Images in Adolescents with Anorexia Nervosa: A Near-Infrared Spectroscopic Study. AB - There have been no reports concerning the self-face perception in patients with anorexia nervosa (AN). The purpose of this study was to compare the neuronal correlates of viewing self-face images (i.e. images of familiar face) and stranger-face images (i.e. images of an unfamiliar face) in female adolescents with and without AN. We used near-infrared spectroscopy (NIRS) to measure hemodynamic responses while the participants viewed full-color photographs of self-face and stranger-face. Fifteen females with AN (mean age, 13.8 years) and 15 age- and intelligence quotient (IQ)-matched female controls without AN (mean age, 13.1 years) participated in the study. The responses to photographs were compared with the baseline activation (response to white uniform blank). In the AN group, the concentration of oxygenated hemoglobin (oxy-Hb) significantly increased in the right temporal area during the presentation of both the self face and stranger-face images compared with the baseline level. In contrast, in the control group, the concentration of oxy-Hb significantly increased in the right temporal area only during the presentation of the self-face image. To our knowledge the present study is the first report to assess brain activities during self-face and stranger-face perception among female adolescents with AN. There were different patterns of brain activation in response to the sight of the self face and stranger-face images in female adolescents with AN and controls. PMID- 26151756 TI - Characteristics of alveolar macrophages from murine models of OVA-induced allergic airway inflammation and LPS-induced acute airway inflammation. AB - BACKGROUND: Macrophages include the classically activated pro-inflammatory M1 macrophages (M1s) and alternatively activated anti-inflammatory M2 macrophages (M2s). The M1s are activated by both interferon-gamma and Toll-like receptor ligands, including lipopolysaccharide (LPS), and have potent pro-inflammatory activity. In contrast, Th2 cytokines activate the M2s, which are involved in the immune response to parasites, promotion of tissue remodeling, and immune regulatory functions. Although alveolar macrophages (AMs) play an essential role in the pulmonary immune system, little is known about their phenotypes. METHODS: Quantitative reverse transcription polymerase chain reaction and flow cytometry were used to define the characteristics of alveolar macrophages derived from untreated naive mice and from murine models of both ovalbumin (OVA)-induced allergic airway inflammation and LPS-induced acute airway inflammation. AMs were co-cultured with CD4(+) T cells and were pulsed with tritiated thymidine to assess proliferative responses. RESULTS: We characterized in detail murine AMs and found that these cells were not completely consistent with the current M1 versus M2-polarization model. OVA-induced allergic and LPS-induced acute airway inflammation promoted the polarization of AMs towards the current M2-skewed and M1-skewed phenotypes, respectively. Moreover, our data also show that CD11c(+) CD11b(+) AMs from the LPS-treated mice play a regulatory role in antigen-specific T-cell proliferation in vitro. CONCLUSIONS: These characteristics of AMs depend on the incoming pathogens they encounter and on the phase of inflammation and do not correspond to the current M1 versus M2-polarization model. These findings may facilitate an understanding of their contributions to the pulmonary immune system in airway inflammation. PMID- 26151757 TI - Tuning Interchain Interactions in Two-Dimensional Networks of Mn(III) Schiff-Base Complexes and Dicarboxylic Acids by Varying the Linker. AB - Two-dimensional (2D) coordination polymers consisting of Mn(III) Schiff-base complexes and dicarboxylic acids, [{Mn(salen)}4(L1)](PF6)2.(CH3OH)2 (C4; H2L1 = adipid acid) and [{Mn(salen)}4(L2)](PF6)2.(CH3OH)4 (C4'; H2L2 = E,E-1,3-butadiene 1,4-dicarboxylic acid) (salen(2-) = N,N'-(ethylene)bis(salicylideneiminato), were synthesized by using a one-pot reaction and characterized by using single-crystal X-ray crystallographic analysis. One-dimensional (1D) chains composed of Mn(salen) dimers, [Mn2], bridged by carboxylato ligands (-[Mn2]-OCO--[Mn2]-), were linked by dicarboxylato ligands with n-butyl (-C4H8-) (C4) and butadienyl aliphatic groups (-C4H4-) (C4'). From static magnetic measurements on both C4 and C4', there were ferromagnetic interactions between the Mn(III) ions through the phenoxo oxygen atoms of the salen(2-), and antiferromagnetic interactions between the Mn(III) ions through carboxylato ligands (-OCO-). As a result, weak ferromagnetism occurred because of the zigzag-shaped chain structure of C4 and C4', and magnetic anisotropy for Mn(salen). In the magnetization curves for C4', weak interchain interactions (Jlinker) occurred through the pi-conjugated butadienyl linkers in C4', which C4 did not have. In other words, changing from saturated to unsaturated aliphatic groups in the dicarboxylic acid linkers resulted in weak interactions between 1D-magnetic chain moieties. Therefore, in the case of only C4', antiferromagnetic phase transition appeared at 2.3 K. Both coordination polymers exhibited slow relaxation of the magnetizations, which originated from SCM moieties, because C4 and C4' showed magnetic correlations. It is noteworthy that alternating current (ac) susceptibilities for C4' are frequency-dependent around the Neel temperature. From analysis of the ac susceptibilities for C4, alpha (dispersion coefficient of the relaxation of magnetization) varied linearly with 1/T. This signifies that C4 behaved as an SCM with a single relaxation process. On the other hand, in alpha versus 1/T plots for C4', an inflection point was observed at the Neel temperature, indicating that Jlinkers had an effect on the distribution of the relaxation times. Moreover, the inflection point for C4' disappeared when a dc magnetic field was applied. This is the first report showing a direct correlation between an antiferromagnetic phase transition and slow magnetic relaxation. PMID- 26151759 TI - Clinical features and treatment outcome of very elderly patients over 80 years old with multiple myeloma: comparison with patients in different age groups in the era of novel agents. AB - We retrospectively analyzed the outcomes of 175 consecutive patients admitted to our hospital between April 2004 and June 2014, and identified 42 (24%), 80 (46%), and 53 (30%) patients >= 80, 66-79, and <= 65 years old, respectively. The median progression-free survival (PFS) and overall survival (OS) of the >= 80, 66-79, and <= 65 years old groups were 19.1, 26.3, and 54.3 months, and 31.9, 54.8, and 83.8 months, respectively. Patients >= 80 but not <= 79 years old with ECOG performance score (PS) >= 3 and/or Charlson comorbidity index (CCI) >= 5 showed significantly shorter survival. ECOG PS and CCI predicted the treatment outcome of patients >= 80 but did not predict <= 79 years old. PMID- 26151758 TI - Genomic modulators of gene expression in human neutrophils. AB - Neutrophils form the most abundant leukocyte subset and are central to many disease processes. Technical challenges in transcriptomic profiling have prohibited genomic approaches to date. Here we map expression quantitative trait loci (eQTL) in peripheral blood CD16+ neutrophils from 101 healthy European adults. We identify cis-eQTL for 3281 neutrophil-expressed genes including many implicated in neutrophil function, with 450 of these not previously observed in myeloid or lymphoid cells. Paired comparison with monocyte eQTL demonstrates nuanced conditioning of genetic regulation of gene expression by cellular context, which relates to cell-type-specific DNA methylation and histone modifications. Neutrophil eQTL are markedly enriched for trait-associated variants particularly autoimmune, allergy and infectious disease. We further demonstrate how eQTL in PADI4 and NOD2 delineate risk variant function in rheumatoid arthritis, leprosy and Crohn's disease. Taken together, these data help advance understanding of the genetics of gene expression, neutrophil biology and immune-related diseases. PMID- 26151760 TI - Treatment of Women With an Endometrial Polyp and Heavy Menstrual Bleeding: A Levonorgestrel-Releasing Intrauterine Device or Hysteroscopic Polypectomy? AB - We performed a literature review of reports comparing a levonorgestrel-releasing intrauterine device (LNG-IUD) with transcervical polyp resection (TCRP) as a treatment for heavy menstrual bleeding (HMB). Our second objective was to investigate the effectiveness of LNG-IUD and TCRP in reducing menstrual bleeding and the patient satisfaction with each technique. No previously reported studies have compared TCRP and LNG-IUD as treatment for HMB in premenopausal women with an endometrial polyp. Likewise, no studies are available on LNG-IUD as a treatment for HMB in the presence of an endometrial polyp. Several studies have found the LNG-IUD to be an effective treatment option for HMB, with high patient satisfaction rates. Evidence of the effectiveness of TCRP as treatment of HMB is scarce. Patient satisfaction is reported relatively good, although persistent or recurrent symptoms appear to be frequent. We conclude that no evidence is available on LNG-IUD as treatment for HMB in women with an endometrial polyp. We hypothesize that LNG-IUD could be a good alternative to TCRP for treating HMB in premenopausal women with a polyp; however, further evidence is needed, and a randomized controlled trial should be performed. PMID- 26151761 TI - Visual recognition memory: a view from V1. AB - Although work in primates on higher-order visual areas has revealed how the individual and concerted activity of neurons correlates with behavioral reports of object recognition, very little is known about the underlying mechanisms for visual recognition memory. Low-level vision, even as early as primary visual cortex (V1) and even in subjects as unsophisticated as rodents, promises to fill this void. Although this latter approach sacrifices interrogation of many of the most astounding features of visual recognition, it does provide experimental constraint, proximity to sensory input, and a wide range of interventional approaches. The tractability of rodent visual cortex promises to reveal the molecular mechanisms and circuits that are essential for a fundamental form of memory. PMID- 26151763 TI - Expression of nephrin in the human placenta and fetal membranes. AB - Nephrin is the signature molecule in the podocyte of the glomerulus that forms the renal slit diaphragm, the main functional unit of the glomerulus. The present study focused on the expression of nephrin in the human placenta, which may also have a role in filtration and the maintenance of homeostasis in the kidneys. A total of nine placentas from normal healthy pregnant females at full term were investigated. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were performed. The expression of nephrin mRNA was relatively increased in the chorion compared with that in the villi and the amnion. The nephrin gene was detected in the villous cytotrophoblast cells and the endothelium of the intravillous vessels. It was also present in the chorionic and amniotic membranous lining, with its distribution being particularly dense in the amniocytes. The identification of nephrin in the human placenta, particularly at the maternal-fetal interface, provides a novel insight into the molecular basis of the selective permeability of the placental barrier, which requires further elucidation. PMID- 26151762 TI - The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma. AB - Understanding the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) may provide therapeutic strategies for this deadly disease. Recently, we and others made the surprising finding that PDAC and its preinvasive precursors, pancreatic intraepithelial neoplasia (PanIN), arise via reprogramming of mature acinar cells. We therefore hypothesized that the master regulator of acinar differentiation, PTF1A, could play a central role in suppressing PDAC initiation. In this study, we demonstrate that PTF1A expression is lost in both mouse and human PanINs, and that this downregulation is functionally imperative in mice for acinar reprogramming by oncogenic KRAS. Loss of Ptf1a alone is sufficient to induce acinar-to-ductal metaplasia, potentiate inflammation, and induce a KRAS permissive, PDAC-like gene expression profile. As a result, Ptf1a-deficient acinar cells are dramatically sensitized to KRAS transformation, and reduced Ptf1a greatly accelerates development of invasive PDAC. Together, these data indicate that cell differentiation regulators constitute a new tumor suppressive mechanism in the pancreas. PMID- 26151764 TI - Irrigation Water Quality for Leafy Crops: A Perspective of Risks and Potential Solutions. AB - There is increasing evidence of the contribution of irrigation water in the contamination of produce leading to subsequent outbreaks of foodborne illness. This is a particular risk in the production of leafy vegetables that will be eaten raw without cooking. Retailers selling leafy vegetables are increasingly targeting zero-risk production systems and the associated requirements for irrigation water quality have become more stringent in regulations and quality assurance schemes (QAS) followed by growers. Growers can identify water sources that are contaminated with potential pathogens through a monitoring regime and only use water free of pathogens, but the low prevalence of pathogens makes the use of faecal indicators, particularly E. coli, a more practical approach. Where growers have to utilise water sources of moderate quality, they can reduce the risk of contamination of the edible portion of the crop (i.e., the leaves) by treating irrigation water before use through physical or chemical disinfection systems, or avoid contact between the leaves and irrigation water through the use of drip or furrow irrigation, or the use of hydroponic growing systems. This study gives an overview of the main problems in the production of leafy vegetables associated with irrigation water, including microbial risk and difficulties in water monitoring, compliance with evolving regulations and quality standards, and summarises the current alternatives available for growers to reduce microbial risks. PMID- 26151765 TI - Valproic acid exposure leads to upregulation and increased promoter histone acetylation of sepiapterin reductase in a serotonergic cell line. AB - Valproic acid (VPA) is a widely used antiepileptic drug and first-line treatment in bipolar disorder, although the mechanisms underlying its therapeutic effects are largely unknown. Recently, the recognition of VPA as an epigenetic drug offers new opportunities for understanding its therapeutic actions. In a rat serotonergic cell line (RN46A) we observed that VPA exposure has a strong upregulatory effect on the gene for sepiapterin reductase (SPR), a key enzyme involved in the tetrahydrobiopterin (BH4) synthetic pathway. BH4 is an essential cofactor in the biosynthesis of neurotransmitters like serotonin, dopamine and noradrenalin, and the BH4 pathway may thus be important in mood biology. Using real-time quantitative PCR we show that VPA, at therapeutically relevant doses, increases the expression of the Spr gene by about 8-fold in RN46A cells. In addition, Spr protein levels in VPA-exposed cells were elevated, as were the intracellular BH4 levels. HDAC inhibitors (HDACI) trichostatin A and sodium butyrate also upregulated Spr, but this was not observed using the VPA-analogue valpromide, which lacks HDAC inhibitory activity. Further examination of this effect revealed that exposure to VPA increased the acetylated histone mark H3K9/K14ac at the Spr promoter. The DNMT inhibitor 5'aza-dC also upregulated Spr by over 8-fold. However, DNA methylation status across the Spr promoter did not change in response to VPA. The BH4 pathway is fundamental to the regulation of neurotransmitters relevant to mood disorders, and this epigenetic effect of VPA at the Spr promoter may represent a novel mechanism through which VPA achieves its therapeutic action. PMID- 26151766 TI - Single dose oral diclofenac for acute postoperative pain in adults. AB - BACKGROUND: Diclofenac is a nonsteroidal anti-inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the stomach). This review updates an earlier review published in the Cochrane Database of Systematic Reviews (Issue 2, 2009) entitled 'Single dose oral diclofenac for acute postoperative pain in adults'. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of diclofenac for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 9 March 2015. SELECTION CRITERIA: Randomised, double blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either diclofenac or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. MAIN RESULTS: This update included three new studies, providing a 26% increase in participants in comparisons between diclofenac and placebo. We included 18 studies involving 3714 participants, 1902 treated with diclofenac and 1007 with placebo. This update has also changed the focus of the review, examining the effects of formulation in more detail than previously. This is a result of increased understanding of the importance of speed of onset in determining analgesic efficacy in acute pain.The largest body of information, for diclofenac potassium 50 mg, in seven studies, produced an NNT for at least 50% of maximum pain relief compared with placebo of 2.1 (95% confidence interval (CI) 1.9 to 2.5) (high quality evidence). There was a graded improvement in efficacy as doses rose from 25 mg to 100 mg, both for participants achieving at least 50% maximum pain relief, and for remedication within 6 to 8 hours. Fast-acting formulations (dispersible products, solutions, and softgel formulations) had a similar efficacy for a 50 mg dose, with an NNT of 2.4 (2.0 to 3.0). Diclofenac sodium in a small number of studies produced a lesser effect, with an NNT of 6.6 (4.1 to 17) for the 50 mg dose.Adverse event rates were low in these single dose studies, with no difference between diclofenac and placebo (moderate quality evidence). AUTHORS' CONCLUSIONS: Diclofenac potassium provides good pain relief at 25 mg, 50 mg, and 100 mg doses. Diclofenac sodium has limited efficacy and should probably not be used in acute pain. PMID- 26151767 TI - Microsecond protein dynamics observed at the single-molecule level. AB - How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape. PMID- 26151768 TI - Roscovitine has anti-proliferative and pro-apoptotic effects on glioblastoma cell lines: A pilot study. AB - Purine analogue roscovitine, a cyclin-dependent kinase (CDK) inhibitor, has shown strong anti-proliferative and pro-apoptotic effects in solid and hematologic cancers such as non small-cell lung cancer and lymphomas. It targets CDK2, 7 and 9 preferentially, which are also overexpressed in glioblastoma. Tauherefore, the biological effects of roscovitine in glioblastoma cell lines were investigated. Glioblastoma A172 and G28 cell lines were incubated with serial concentrations of roscovitine for 24-120 h. Proliferation was measured using the xCELLigence Real Time Cell Analyzer, an impedance-based cell viability system. Cell cycle distribution was assessed by flow cytometry and gene expression was quantified by quantitative RT-PCR and western blot analysis. Roscovitine exhibited a clear dose dependent anti-proliferative and pro-apoptotic effect in the A172 cell line, while G28 cells showed a anti-proliferative effect only at 100 uM. The results of the flow cytometric (FACS) analysis revealed a dose-dependent increase of the G2/M and sub-G1 fractions in A172 cells, while G28 cells responded with an elevated sub-G1 fraction only at the highest concentration. Roscovitine led to a dose-dependent decrease of transcripts of p53, CDK 7 and cyclins A and E and an increase of >4-fold of p21 in A172 cells. In G28 cells, a dose-dependent induction of CDK2, p21 and cyclin D was observed between 10 and 50 uM roscovitine after 72 h, however, at the highest concentration of 100 uM, all investigated genes were downregulated. Roscovitine exerted clear dose-dependent anti proliferative and pro-apoptotic effects in A172 cells and less distinct effects on G28 cells. In A172 cells, roscovitine led to G2/M arrest and induced apoptosis, an effect accompanied by induced p21 and a reduced expression of CDK2, 7 and 9 and cyclins A and E. These effects requre further studies on a larger scale to confirm whether roscovitine can be used as a therapeutic agent against glioblastoma. PMID- 26151769 TI - A Ground-Up Model for Gun Violence Reduction: A Community-Based Public Health Approach. AB - The suggested strategy for the reduction of violence is to collaboratively address the problem, based on an intervention system focused on prevention, rehabilitation, and development. This strategy is capable of engaging community residents in positive ways, and it empowers them to take ownership and sustain much-needed resident commitments to achieve long-term public safety. The community residents largely insist that over-reliance on law enforcement to control violence invites further affliction among Black youth and adults. PMID- 26151770 TI - Exercise suppresses COX-2 pro-inflammatory pathway in vestibular migraine. AB - Migraine and dizziness are relatively common disorders. Patients with dizziness have a higher incidence of migraines than the general population. The discomfort experienced by these patients is often poorly controlled by medication. However, the pathophysiology of vestibular migraine (VM) remains unclear. We hypothesized that patients with VM would experience remission from symptoms after exercise training and that this effect may be mediated through the suppression of cyclooxygenase-2 (COX-2)-mediated inflammation. Thus, the aim of the present study was to investigate the efficacy and possible anti-inflammatory benefits of exercise in patients with VM. We assessed the level of soluble inflammatory mediators in plasma from VM patients and control subjects. Our analysis of cytokine expression in the patients with VM undergoing exercise treatment revealed a significant reduction in pro-inflammatory cytokines and/or cytotoxic factors, such as tumor necrosis factor-alpha, interleukins, nitric oxide (NO), inducible NO synthase, and reactive oxygen species. In contrast, we found an increase in the level of anti-inflammatory cytokines after exercise. Moreover, the group undergoing exercise training showed significant symptomatic improvement and demonstrated suppressed antioxidant enzyme activity. To summarize, our data suggest that exercise significantly inhibits COX-2 activity, leading to the suppression of pro-inflammatory cytokines and changes in redox status. These results suggest that there is a molecular link between the central nervous system and the immune system. Furthermore, elucidation of the neurobiological mechanisms underlying VM could potentially lead to the development of novel therapeutic interventions for these patients. PMID- 26151771 TI - Spinal cord injury affects I-wave facilitation in human motor cortex. AB - Transcranial magnetic stimulation (TMS) is a useful non-invasive approach for studying cortical physiology. To further clarify the mechanisms of cortical reorganization after spinal cord injury (SCI), we used a non-invasive paired TMS protocol for the investigation of the corticospinal I-waves, the so-called I-wave facilitation, in eight patients with cervical SCI. We found that the pattern of I wave facilitation significantly differs between SCI patients with normal and abnormal central motor conduction (CMCT), and healthy controls. The group with normal CMCT showed increased I-wave facilitation, while the group with abnormal CMCT showed lower I-wave facilitation compared to a control group. The facilitatory I-wave interaction occurs at the level of the motor cortex, and the mechanisms responsible for the production of I-waves are under control of GABA related inhibition. Therefore, the findings of our small sample preliminary study provide further physiological evidence of increased motor cortical excitability in patients with preserved corticospinal projections. This is possibly due to decreased GABAergic intracortical inhibition. The excitability of networks producing short-interval intracortical facilitation could increase after SCI as a mechanism to enhance activation of residual corticospinal tract pathways and thus compensate for the impaired ability of the motor cortex to generate appropriate voluntary movements. Finally, the I-wave facilitation technique could be used in clinical neurorehabilitation as an additional method of assessing and monitoring function in SCI. PMID- 26151772 TI - Immature large ribosomal subunits containing the 7S pre-rRNA can engage in translation in Saccharomyces cerevisiae. AB - Evolution has provided eukaryotes with mechanisms that impede immature and/or aberrant ribosomes to engage in translation. These mechanisms basically either prevent the nucleo-cytoplasmic export of these particles or, once in the cytoplasm, the release of associated assembly factors, which interfere with the binding of translation initiation factors and/or the ribosomal subunit joining. We have previously shown that aberrant yeast 40S ribosomal subunits containing the 20S pre-rRNA can engage in translation. In this study, we describe that cells harbouring the dob1-1 allele, encoding a mutated version of the exosome-assisting RNA helicase Mtr4, accumulate otherwise nuclear pre-60S ribosomal particles containing the 7S pre-rRNA in the cytoplasm. Polysome fractionation analyses revealed that these particles are competent for translation and do not induce elongation stalls. This phenomenon is rather specific since most mutations in other exosome components or co-factors, impairing the 3' end processing of the mature 5.8S rRNA, accumulate 7S pre-rRNAs in the nucleus. In addition, we confirm that pre-60S ribosomal particles containing either 5.8S + 30 or 5.8S + 5 pre rRNAs also engage in translation elongation. We propose that 7S pre-rRNA processing is not strictly required for pre-60S r-particle export and that, upon arrival in the cytoplasm, there is no specific mechanism to prevent translation by premature pre-60S r-particles containing 3' extended forms of mature 5.8S rRNA. PMID- 26151773 TI - Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA mediated suppression of ATG10. AB - Burkholderia pseudomallei is the causative agent of melioidosis, a disease with high mortality, which is prevalent in tropical regions of the world. A recent study shows that B. pseudomallei can survive inside mammalian cells because of its ability to actively evade cell autophagy. However, the underlying mechanisms remain unclear. In the present study, based on microarray screening, we found that ATG10 was downregulated following B. pseudomallei infection in A549 human lung epithelial cells. Forced expression of ATG10 accelerated the elimination of intracellular B. pseudomallei by enhancing the process of autophagy. Moreover, MIR4458, MIR4667-5p, and MIR4668-5p were found, by microarray screening, to be upregulated in response to B. pseudomallei infection. These 3 novel miRNAs, MIR4458, MIR4667-5p, and MIR4668-5p, targeted to the 3'-untranslated region of ATG10 in different time-course and spatial manners. Upregulation of these miRNAs reduced the level of ATG10 and inhibited autophagy, leading to increasing survival rate of intracellular B. pseudomallei. Furthermore, the increase of these miRNAs was correlated with the reduced promoter methylation status in A549 cells in response to B. pseudomallei infection. Our results reveal that 3 novel miRNAs regulate autophagy-mediated elimination of B. pseudomallei by targeting ATG10, and provide potential targets for clinical treatment. PMID- 26151774 TI - The C-terminal domains of two homologous Oleaceae beta-1,3-glucanases recognise carbohydrates differently: Laminarin binding by NMR. AB - Ole e 9 and Fra e 9 are two allergenic beta-1,3-glucanases from olive and ash tree pollens, respectively. Both proteins present a modular structure with a catalytic N-terminal domain and a carbohydrate-binding module (CBM) at the C terminus. Despite their significant sequence resemblance, they differ in some functional properties, such as their catalytic activity and the carbohydrate binding ability. Here, we have studied the different capability of the recombinant C-terminal domain of both allergens to bind laminarin by NMR titrations, binding assays and ultracentrifugation. We show that rCtD-Ole e 9 has a higher affinity for laminarin than rCtD-Fra e 9. The complexes have different exchange regimes on the NMR time scale in agreement with the different affinity for laminarin observed in the biochemical experiments. Utilising NMR chemical shift perturbation data, we show that only one side of the protein surface is affected by the interaction and that the binding site is located in the inter helical region between alpha1 and alpha2, which is buttressed by aromatic side chains. The binding surface is larger in rCtD-Ole e 9 which may account for its higher affinity for laminarin relative to rCtD-Fra e 9. PMID- 26151775 TI - The role of Myc and let-7a in glioblastoma, glucose metabolism and response to therapy. AB - Glioblastoma multiforme (GBM) is thought to result from an imbalance between glucose metabolism and tumor growth. The Myc oncogene and lethal-7a microRNA (let 7a miRNA) have been suggested to cooperatively regulate multiple downstream targets leading to changes in chromosome stability, gene mutations, and/or modulation of tumor growth. Here, we review the roles of Myc and let-7a in glucose metabolism and tumor growth and addresses their future potential as prognostic markers and therapeutic tools in GBM. We focus on the functions of Myc and let-7a in glucose uptake, tumor survival, proliferation, and mobility of glioma cells. In addition, we discuss how regulation of different pathways by Myc or let-7a may be useful for future GBM therapies. A large body of evidence suggests that targeting Myc and let-7a may provide a selective mechanism for the deregulation of glucose metabolic pathways in glioma cells. Indeed, Myc and let 7a are aberrantly expressed in GBM and have been linked to the regulation of cell growth and glucose metabolism in GBM. This article is part of a Special Issue entitled "Targeting alternative glucose metabolism and regulate pathways in GBM cells for future glioblastoma therapies". PMID- 26151776 TI - Next-generation sequencing: Application of a novel platform to analyze atypical iron disorders. AB - The development of targeted next-generation sequencing (NGS) applications now promises to be a clinically viable option for the diagnosis of rare disorders. This approach is proving to have significant utility where standardized testing has failed to identify the underlying molecular basis of disease. We have developed a unique targeted NGS panel for the systematic sequence-based analysis of atypical iron disorders. We report the analysis of 39 genes associated with iron regulation in eight cases of atypical iron dysregulation, in which five cases we identified the definitive causative mutation, and a possible causative mutation in a sixth. We further provide a molecular and cellular characterization study of one of these mutations (TFR2, p.I529N) in a familial case as proof of principle. Cellular analysis of the mutant protein indicates that this amino acid substitution affects the localization of the protein, which results in its retention in the endoplasmic reticulum and thus failure to function at the cell surface. Our unique NGS panel presents a rapid and cost-efficient approach to identify the underlying genetic cause in cases of atypical iron homeostasis disorders. PMID- 26151777 TI - HIV and mucosal barrier interactions: consequences for transmission and pathogenesis. AB - The mucosal barrier plays an integral function in human health as it is the primary defense against pathogens, and provides a critical transition between the external environment and the human internal body. In the context of HIV infection, the most relevant mucosal surfaces include those of the gastrointestinal (GI) and genital tract compartments. Several components help maintain the effectiveness of this mucosal surface, including the physical anatomy of the barrier, cellular immunity, soluble factors, and interactions between the epithelial barrier and the local microenvironment, including mucus and host microbiota. Any defects in barrier integrity or function can rapidly lead to an increase in acquisition risk, or with established infection may result in increased pathogenesis, morbidities, or mortality. Indeed, a key feature to all aspects of HIV infection from transmission to pathogenesis is disruption and/or dysfunction of mucosal barriers. Herein, we will detail the host-pathogen relationship of HIV and mucosal barriers in both of these scenarios. PMID- 26151779 TI - Wound Healing. PMID- 26151780 TI - The Value of the Black Box Warning in Dermatology. AB - Boxed, or "black box" warnings are issued by the United States Food and Drug Administration (US FDA) as a means to label drugs associated with serious adverse events. However, there is no clear metric to determine how and when the boxed warning is applied. Inconsistencies in the review process, language, timing, and dissemination of these warnings impact dermatologists and their patients. Appropriate patient selection and monitoring can help minimize risk to patients when prescribing drugs with boxed warnings. Future changes in the manner in which the boxed warning is issued and in its subsequent clinical application may improve the utility of these warnings for dermatologists and ultimately, patient safety. PMID- 26151781 TI - The Potential Role of Topically Applied Heparan Sulfate in the Treatment of Photodamage. AB - Heparan sulfate is an essential glycosaminoglycan that plays important roles in development, homeostasis, and disease. As a group, the glycosaminoglycans provide mechanical strength to skin, as they can absorb water and occupy the space between elastin fibers and collagen. Heparan sulfate is also a key participant in cell proliferation, cell migration, collagen fiber formation, basement membrane regeneration, granulation tissue formation, and cell adhesion associated with wound healing. A variety of dermatological disorders are associated with changes in glycosaminoglycans or their associated proteoglycans. A new topical formulation of low molecular weight heparan sulfate glycosaminoglycan has been shown to penetrate the epidermis, basement membrane, and dermis within 24 hours of application. In an 8-week study, 15 patients using this new formulation showed improvement in skin hydration, skin firmness, skin elasticity, skin barrier function, and global fine lines and wrinkles. Incorporating low molecular weight heparan sulfate into topically applied formulations may represent a new approach to improving the appearance of photodamaged skin. PMID- 26151782 TI - In Vitro Nail Penetration of Tavaborole Topical Solution, 5%, Through Nail Polish on Ex Vivo Human Fingernails. AB - BACKGROUND: Onychomycosis is a common infection of the toenails that causes nail thickening and discoloration. The physical appearance of the infected nail can diminish self-image and negatively impact quality of life. Patients may use nail polish to mask the appearance of infected nails. OBJECTIVE: To evaluate the in vitro nail penetration properties of tavaborole topical solution, 5%, through nail polish using ex vivo, non-diseased human fingernails. METHODS: In study 1, tavaborole penetration was evaluated over 20 days of dosing using the Franz finite dose technique and modified Franz diffusion cells. Nails received either 1 coat of over-the-counter (OTC) typical polish or were left unpolished (controls). In study 2, tavaborole penetration was measured over 14 days of dosing using the finite dose technique and vertical diffusion cells. Nails were polished with either 4 coats or 1 coat of salon typical polish or with 2 coats or 1 coat of OTC typical polish, or they were left unpolished. RESULTS: In study 1, the mean +/- standard deviation (SD) cumulative tavaborole penetration at day 21 was numerically higher, though not statistically significant, through polished nails (3,526 +/- 1,433 MUg/cm(2))vs unpolished nails (2,661 +/- 1,319 MUg/cm(2)).In study 2, the mean cumulative tavaborole penetration was also numerically higher (statistical significance not assessed) through all nails that received polish vs unpolished nails. At day 15, mean +/- SD cumulative tavaborole nail penetration was 1,179 +/- 554 MUg/cm(2) through 4 coats of salon typical polish, 1,227 +/- 974 MUg/cm(2) through 1 coat of salon typical polish, 1,493 +/- 1,322 MUg/cm(2) through 2 coats of OTC typical polish, 1,428 +/- 841 MUg/cm(2) through 1 coat of OTC typical polish, and 566 +/- 318 MUg/cm(2) through unpolished nails. CONCLUSION: Results from these in vitro studies demonstrated that tavaborole penetrated through human nails with up to 4 layers of nail polish. PMID- 26151783 TI - Severe Autoimmune Adverse Events Post Herpes Zoster Vaccine: A Case-Control Study of Adverse Events in a National Database. AB - Zoster vaccine is recommended to reduce the incidence of herpes zoster and its complication of postherpetic neuralgia in older adults. However, there have been reports of autoimmune side effects post vaccination. We therefore aim to investigate the possible relationship of severe autoimmune adverse events (arthritis, vasculitis, systemic lupus erythematosus, thrombocytopenia, alopecia, Guillain-Barre syndrome, optic neuritis and multiple sclerosis) post zoster vaccination with a matched case-control study of reported events in the Vaccine Adverse Event Reporting System (VAERS). Our study showed no significantly increased risks of severe autoimmune adverse events, except arthritis and alopecia, after vaccination. Compared to the unexposed, patients with zoster vaccination had 2.2 and 2.7 times the odds of developing arthritis and alopecia, respectively (P<0.001 and P=0.015, respectively). However, almost none of these events was life threatening. Zoster vaccine is, therefore, relatively safe and unlikely to exacerbate or induce autoimmune diseases. Given its benefits and safety but low coverage, dermatologists and primary care physicians should encourage zoster vaccine use in elderly patients, including selected patients with autoimmune diseases. PMID- 26151784 TI - An Open-Label, Multi-Center, Multiple-Application Pharmacokinetic Study of Naftifine HCl Gel 2% in Pediatric Subjects With Tinea Pedis. AB - BACKGROUND: Tinea pedis is the most common superficial fungal infection. Naftifine hydrochloride is a topical antifungal of the allylamine class, displaying fungicidal activity and clinically significant anti-bacterial and anti inflammatory effects. Clinical data on topical antifungal therapy using naftifine for tinea pedis in a pediatric population is limited. OBJECTIVE: To assess trends in efficacy, tolerability, safety, and to quantify the pharmacokinetics (PK) of topical naftifine hydrochloride gel 2% in pediatric subjects with tinea pedis. METHODS: Twenty-eight subjects (22 pediatric and 6 adult controls) were enrolled and treated in the study. Approximately 2 grams of naftifine hydrochloride gel 2% was applied to each foot (4 grams total) for subjects with tinea pedis. Pharmacokinetic blood and urine samples were collected at various time points throughout the study. Efficacy was assessed based on potassium hydroxide, dermatophyte culture, and signs and symptom results at days 7, 14, and 28. Adverse event information was collected routinely.
RESULTS: The rate and extent of systemic exposure among the pediatric and adult control subjects was low. Adverse events were minimal and were not related to treatment. Positive results were observed as early as day 7; however the proportion of subjects achieving success generally increased over time through day 28 in both treatment groups. CONCLUSIONS: Naftifine hydrochloride gel 2% was found to be well tolerated and safe. Trends in clinical benefit were observed throughout the treatment period; however, continued improvement in efficacy rates were observed during the post-treatment period. PMID- 26151785 TI - Managing Assessments and Expectations: Patient Responses Following Therapy With Efinaconazole Topical Solution, 10%. AB - INTRODUCTION: Successful treatment of onychomycosis is both a clinical and therapeutic challenge. Effective patient education and reassurance are critical. This post hoc analysis aims to provide some guidance to physicians based on initial disease severity and influencing factors. METHODS: A post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled studies evaluating the efficacy and safety of efinaconazole topical solution, 10% in mild to moderate onychomycosis. Outcomes were assessed based on baseline severity (20% 29%, 30%-39%, 40%-49%, and >=50% affected target toenail). RESULTS: Overall, the mean percent affected toenail following efinaconazole treatment decreased from 36.4% to 20.6% (a 43% reduction). The percent reduction in mean percent affected toenail (range, 43.6% to 59.8%) with efinaconazole was similar irrespective of baseline severity. Improvement was only seen in the very mildest patients with vehicle and not before week 36. Improvement was influenced by gender (females did better) and disease duration (long standing disease responding less well). CONCLUSIONS: Our onychomycosis patients treated with efinaconazole might expect a 50% improvement in their disease within a year, and this will be seen as significant by many, especially those who have suffered for many years. Many will do better, but they will need to be reminded of the slow growth of the toenail. PMID- 26151786 TI - An Open Label Clinical Trial of a Multi-Ingredient Anti-Aging Moisturizer Designed to Improve the Appearance of Facial Skin. AB - An open label clinical trial was conducted to determine the effectiveness of a multi-ingredient anti-aging moisturizer designed to improve the appearance of facial skin. Parameters studied included fine lines and wrinkles, clarity/brightness, visual roughness, tactile roughness, evenness of skin tone (redness), evenness of skin tone (hyperpigmentation) and overall appearance. Thirty-seven female subjects, ages 35-60 years completed the study. Effective ingredients incorporated into the facial anti-aging moisturizer include: Astragalus membranaceus root extract, a peptide blend including palmitoyl tripeptide-38, standardized rosemary leaf extract (ursolic acid), tetrahexyldecyl ascorbate (THD ascorbate) and ubiquinone (coenzyme Q10). Subjects were instructed to apply the moisturizer twice daily, once in the morning and once in the evening. Subjects were evaluated at baseline and after 4, 8, and 12 weeks of product usage. Clinical evaluations were conducted at each visit. A self assessment questionnaire was conducted at week 4, week 8, and week 12. The self assessment questionnaire included product efficacy inquiries and product aesthetic inquiries. Digital photography was conducted at baseline, week 8, and week 12. After 8 weeks of twice daily use, clinical evaluation results show that the multi-ingredient anti-aging moisturizer produced a statistically significant improvement in the scores of all clinical grading parameters assessed compared to baseline. A greater statistically significant improvement was seen at 12 weeks. At week 12, there was a statistically significant percentage of favorable results versus unfavorable results in all product efficacy and product aesthetic self assessment questionnaire results. Digital photography supported the clinical grading and self-assessment questionnaire results. Additionally, the multi ingredient anti-aging moisturizer is judged to be mild and well tolerated. Several tolerability parameters were assessed at all time points with no statistically significant increase in any of the scores compared to baseline. PMID- 26151787 TI - Safety Surveillance for Ustekinumab and Other Psoriasis Treatments From the Psoriasis Longitudinal Assessment and Registry (PSOLAR). AB - BACKGROUND: Safety surveillance is needed for biologic therapies for psoriasis. OBJECTIVE: To assess the risk of adverse events of special interest (AEoSIs) with ustekinumab and other psoriasis treatments in a real-world setting using 2014 Psoriasis Longitudinal Assessment and Registry (PSOLAR) data. AEoSIs included malignancy (excluding nonmelanoma skin cancer), major adverse cardiovascular events (MACE), serious infection, and all-cause mortality. METHODS: Cumulative rates of AEoSIs/100 patient-years (PY) are reported for ustekinumab, infliximab, other biologics (mostly adalimumab/etanercept), and non-biologics based on pre specified analyses using attribution rules biased against ustekinumab. Risk factors for AEoSIs, including treatments, were determined using multivariate statistical analysis. RESULTS: A total of 12,093 patients (40,388 PY) were enrolled in PSOLAR. Overall incidence rates were 0.68/100PY for malignancy, 0.33/100PY for MACE, 1.60/100PY for serious infection, and 0.46/100PY for mortality. Unadjusted rates of serious infection for infliximab (2.91/100PY) and other biologics (1.91/100PY) were numerically higher compared with ustekinumab (0.93/100PY). Exposure to the combined group of biologics other than ustekinumab was significantly associated with serious infection (hazard ratio=1.96, P<.001). None of the biologics was associated with increased risk of malignancy, MACE, or mortality. LIMITATIONS: Observational data have inherent biases. CONCLUSION: Analysis of 2014 PSOLAR data identified no increased risk of malignancy, MACE, serious infection, or mortality with ustekinumab. PMID- 26151788 TI - Identifying an Education Gap in Wound Care Training in United States Dermatology. AB - IMPORTANCE: As restoration of the integument is paramount to wound healing, dermatologists should be central to managing wounds; yet this is often not the case. If a training gap exists during residency training, this may account for the observed discrepancy. OBJECTIVES: To identify United States (US) dermatology residents' impressions regarding their preparedness to care for wounds, and to assess the amount and type of training devoted to wound care during residency. DESIGN, SETTING, AND PARTICIPANTS: An online survey among current US dermatology residents enrolled in a residency training program. MAIN OUTCOMES AND MEASURES: The primary goal was to determine whether dermatology residents believe more wound care education is needed, evaluate preparedness to care for wounds, and identify future plans to manage wounds. RESULTS: Responses were received from 175 of 517 (33.8%) US Dermatology residents contacted. The majority of residents did not feel prepared to manage acute (78.3%) and chronic (84.6%) wounds. Over three quarters (77.1%) felt that more education is needed. Fewer than half (49.1% and 35.4%) of residents planned to care for acute and chronic wounds, respectively, when in practice. CONCLUSIONS AND RELEVANCE: There is a gap in wound care education in US dermatology residency training. This translates to a low percentage of dermatology residents planning to care for wounds in future practice. Dermatology residents need to receive focused wound care training in order to translate the underpinnings of wound healing biology and ultimately better serve patients. PMID- 26151789 TI - The Management of Burn Injuries by Dermatologist: A Single Center Pilot Study. AB - BACKGROUND: Burns are a major cause of morbidity and mortality worldwide. Most burn patients are treated in an outpatient setting. However, the type of burn injuries, frequency of burn injuries treated by dermatologists, and therapeutic approach is unknown. OBJECTIVE: To assess burn injury incidence in a single center academic dermatology practice, and describe demographic characteristics of burn patients seen by dermatologists. METHODS: A retrospective chart review analysis of 51 patients seen by 7 dermatologists from April 2010 to July 2014. RESULTS: Of the 51 patients seen, burns from hot metal were the main mechanism of injury followed by contact with hot liquids. Silver sulfadiazine was the most commonly prescribed treatment. At the time of the visit 84.3% (n=43) had other dermatological conditions. CONCLUSION: Our study demonstrates that burns are not frequently seen by dermatologists. We hypothesize that longer wait times in specialty practices, the lack of burn-specific training and the complexities of burn care prevent dermatologists from being first line providers in this arena. A larger epidemiological study is needed to further elucidate these issues. PMID- 26151790 TI - N-acetylcysteine S-nitrosothiol Nanoparticles Prevent Wound Expansion and Accelerate Wound Closure in a Murine Burn Model. AB - BACKGROUND: The treatment of cutaneous wounds in the clinical setting continues to be a clinical challenge and economic burden, with burn wounds being especially formidable. Direct mechanical injury coupled with the transfer of thermal energy leads to tissue necrosis, pro-inflammatory cytokine release and the eventual expansion of an initial wound. Our current therapeutic armamentarium falls short of options to help prevent wound expansion, and therefore new modalities are required. Nitrosating substances such as RSNOs have been proven to be effective in promoting wound closure due to their ability to modulate inflammation, cytokine production and vascular function. OBJECTIVE: We aim to evaluate the efficacy of n-actetylcysteine s-nitrosothiol nanoparticles (NAC-SNO-np) on thermal burn wounds and associated expansion. METHODS: A multi-burn model was utilized to induce three burn wounds on the dorsal surface of BALB/c mice, allowing for evaluation of the burn itself and peripheral tissue. Wounds were excised and processed for histology and immunohistochemistry on day 7 following wounding. RESULTS: Following treatment with NAC-SNO-np, burn wound expansion was attenuated and wound healing was accelerated. Histological analysis revealed increased collagen deposition as well as increased macrophage and decreased neutrophil infiltration into the wound bed. CONCLUSION: NAC-SNO-np represents a platform that harnesses the nitrosative properties of NAC-SNO in order to accelerate the transition from inflammatory to proliferative wound healing. Further studies are needed in order to translate to the clinical setting. PMID- 26151791 TI - Cryo-Induced Thermal Wounds: A Human Acute Wound Model. AB - INTRODUCTION: Clinical models are invaluable in studying wound healing. Challenges in studying human wounds include heterogeneity of patients and wounds, as well as prolonged study time, resulting in high costs. Animal models are an efficient method to study wound healing, but often lack correlation with human acute wound healing. Human wound models can be created using sharp instruments, suction, acids, heat and cold. In this observational study, we propose a practical human acute wound model where partial thickness wounds are induced by cryosurgery to create wounds that could facilitate wound healing research and development. METHODS: On forearms of 8 healthy adult volunteers, freeze injuries were induced using liquid nitrogen spray delivered onto a target area of a 1 cm circular opening at a distance from the cryo-device to the skin of 0.5-1 cm. Several freeze-thaw time cycles were implemented by administering pulses ranging from 3 to 12 seconds. Clinical evaluation was performed at a 24-hour follow-up period. Blister roofs were histologically analyzed by a blinded dermatophathologist. Clinical assessment of time to heal was determined. RESULTS: Freeze-times greater than 5 seconds caused a majority of subjects to develop blisters, and freeze-times greater than 8 seconds resulted in uniform blister formation. Consistent histology of full thickness necrotic epidermis with intact detached basement membrane with minimal acute neutrophilic inflammatory infiltrate was observed in all blister specimens examined. The 8-second freeze time group had a time to heal of 13-14 days, while the 12-second freeze-time group required 3 weeks to heal. After healing, an area of hypopigmented skin and slightly hypertrophic scarring remained. DISCUSSION: This novel cryo-induced wound model is a potential simple, efficient and reliable model for studying the dynamic processes involved in acute wound healing and to aid in the development of new wound healing therapies. Clinicaltrials.gov identifier: NCT01253135. PMID- 26151792 TI - Systematic Approach to Wound Dressings. AB - Chronic wounds are a major source of morbidity and mortality within the United States. Wound dressings remain a cornerstone of dermatologic therapy. Selection of the proper wound dressing proves difficult given the range of wounds encountered and the numerous dressing options available to the clinician. Nevertheless, selection of a proper wound dressing is a crucial step in management that can significantly alter the course of wound healing. There are a variety of wound dressings available, including moisture retentive/occlusive dressings as well as dressings impregnated with antimicrobial agents. Here we outline the characteristics and indications of specific wound dressings in order to provide clinicians with a basic understanding of the types of dressings available. This review provides a tool for dermatologists to better assess and treat chronic wounds. Using the algorithm provided, clinicians will be able to select the appropriate dressing in order to accelerate wound healing, prevent infection and improve health outcomes. PMID- 26151793 TI - Serum Sirolimus Level Elevation Induced by Acitretin: Report of a Novel Drug-Drug Interaction. AB - Long-term immunosuppression in the organ transplant recipient (OTR) population places these individuals at higher risk of developing skin malignancies. Oral retinoids have become a useful tool for pharmacologic prophylaxis in the OTR population. Immunosuppressants that inhibit mTOR, such as sirolimus, may be used in combination with a systemic retinoid for chemoprophylaxis of cutaneous malignancies. We present the case of a male patient status post second renal transplant who developed an abrupt and unexpected rise in sirolimus levels to supra-therapeutic levels after initiation of prophylactic acitretin for innumerable squamous cell carcinomas (SCC). The sirolimus levels returned to baseline after cessation of acitretin. Systemic drug-drug interactions are an important phenomenon, especially in the solid OTR population. It is postulated that this interaction was mediated by acitretin inhibition of CYP3A4, the primary enzyme responsible for sirolimus metabolism. The Drug Interaction Probability Scale (DIPS) indicates this was a "probable" drug-drug interaction. To date, this interaction has not been reported in the literature. This case accentuates the importance of close monitoring of solid OTRs for adverse medication interactions when multiple medications are taken. PMID- 26151794 TI - Successful Treatment of Idiopathic Onychodystrophy With 300 Microsecond 1064 nm Nd:YAG Laser. AB - Onychodystrophy is the temporary or permanent change in the nail structures. It can be secondary to an inflammatory condition or infectious disease, however many cases of onychodystrophy are idiopathic in nature. In secondary onychodystrophy the treatment is directed towards the underlying process, with subsequent improvement in the appearance of the affected nails depending on the etiology. Dystrophy secondary to onychomycosis is particularly difficult to treat. In permanent idiopathic nail dystrophy, treatment is often unsatisfactory. Destructive nail changes are not only cosmetically displeasing, but also at times physically painful and socially embarrassing. The literature on the treatment of purely idiopathic nail dystrophy is extremely scarce. To our knowledge there exists only one report of two cases of idiopathic onychodystrophy successfully treated with fractional carbon dioxide laser and topical corticosteroids. In this report, we present the first cases of idiopathic onychodystrophy successfully treated with a 1064 nm neodymium-doped yttrium aluminum garnet laser. PMID- 26151795 TI - Total Defense + Repair: A Novel Concept in Solar Protection and Skin Rejuvenation. AB - For more than a century, solar radiation has been known to contribute significantly to the extrinsic aging of skin. Until recently, this was almost exclusively attributed to the photodamage caused by ultraviolet (UV) light. However, a growing body of evidence now indicates that both infrared (IR) and visible light may also contribute to extrinsic skin aging. Infrared radiation, comprised of IR-A, IR-B, and IR-C, accounts for 54.3% of the total solar radiation reaching the skin. Studies have shown that IR radiation is also responsible for skin aging. Thus, IR-A radiation regulates hundreds of genes in skin, with roles in extracellular matrix (ECM) homeostasis regulation, apoptosis, cell growth, and stress responses. IR-B and IR-C radiation are primarily responsible for the increase in skin temperature associated with solar exposure, and are implicated in heat-related skin destruction of collagen and elastin, which is characterized by an increase in the expression of matrix metalloproteinases (MMPs). The contribution of visible light to photoaging is less well understood; however, some preliminary indication associates visible light with the upregulation of MMPs' expression, DNA damage, and keratinocyte proliferation. Interestingly, the common denominator that links skin damage to the different solar wavelengths is the enhanced production of reactive molecule species (RMS) and therewith increased oxidative stress. SkinMedica(r) Total Defense + Repair (TD+R; SkinMedica Inc., an Allergan company, Irvine, CA) is a "superscreen," which combines broad spectrum UV protection with a unique blend of antioxidants (SOL-IR Advanced Antioxidant ComplexTM) that provide protection from IR radiation while promoting skin repair. Preclinical studies have indicated that TD+R SPF34 prevents the formation of UV-induced sunburn cells and cyclobutane pyrimidine dimers while preserving or improving the expression of ECM genes. In addition, it prevents IR-A-triggered fragmentation of elastin fibers and expression of MMP-1. Initial clinical studies indicate that TDR+R SPF34 reduces the increase in surface temperature seen with IR radiation. A significant improvement in the appearance of lines and wrinkles was reported as early as week 2 in patients using TDR+R SPF34. In summary, we observed that the unique blend of antioxidants present in TD+R acts in harmony with SPF active ingredients, expanding solar protection beyond UV radiation and counterbalancing the deleterious effects of free radicals on skin cells by promoting endogenous repair. PMID- 26151796 TI - The Basic-Systems Model of Episodic Memory. AB - Behavior, neuropsychology, and neuroimaging suggest that episodic memories are constructed from interactions among the following basic systems: vision, audition, olfaction, other senses, spatial imagery, language, emotion, narrative, motor output, explicit memory, and search and retrieval. Each system has its own well-documented functions, neural substrates, processes, structures, and kinds of schemata. However, the systems have not been considered as interacting components of episodic memory, as is proposed here. Autobiographical memory and oral traditions are used to demonstrate the usefulness of the basic-systems model in accounting for existing data and predicting novel findings, and to argue that the model, or one similar to it, is the only way to understand episodic memory for complex stimuli routinely encountered outside the laboratory. PMID- 26151797 TI - Introduction to the Special Section: Professional Issues in Psychological Science and a Discussion of Collaboration Indicators. PMID- 26151798 TI - Study of Mathematically Precocious Youth After 35 Years: Uncovering Antecedents for the Development of Math-Science Expertise. AB - This review provides an account of the Study of Mathematically Precocious Youth (SMPY) after 35 years of longitudinal research. Findings from recent 20-year follow-ups from three cohorts, plus 5- or 10-year findings from all five SMPY cohorts (totaling more than 5,000 participants), are presented. SMPY has devoted particular attention to uncovering personal antecedents necessary for the development of exceptional math-science careers and to developing educational interventions to facilitate learning among intellectually precocious youth. Along with mathematical gifts, high levels of spatial ability, investigative interests, and theoretical values form a particularly promising aptitude complex indicative of potential for developing scientific expertise and of sustained commitment to scientific pursuits. Special educational opportunities, however, can markedly enhance the development of talent. Moreover, extraordinary scientific accomplishments require extraordinary commitment both in and outside of school. The theory of work adjustment (TWA) is useful in conceptualizing talent identification and development and bridging interconnections among educational, counseling, and industrial psychology. The lens of TWA can clarify how some sex differences emerge in educational settings and the world of work. For example, in the SMPY cohorts, although more mathematically precocious males than females entered math-science careers, this does not necessarily imply a loss of talent because the women secured similar proportions of advanced degrees and high-level careers in areas more correspondent with the multidimensionality of their ability preference pattern (e.g., administration, law, medicine, and the social sciences). By their mid-30s, the men and women appeared to be happy with their life choices and viewed themselves as equally successful (and objective measures support these subjective impressions). Given the ever-increasing importance of quantitative and scientific reasoning skills in modern cultures, when mathematically gifted individuals choose to pursue careers outside engineering and the physical sciences, it should be seen as a contribution to society, not a loss of talent. PMID- 26151799 TI - What Should I Be Doing, and Where Are They Doing It? Scholarly Productivity of Academic Psychologists. AB - Scholarly productivity is used to index faculty achievement, but normative data on publication rates among academic psychologists are scarce. This article presents the results of a study of 1,216 faculty members from 96 schools, ranging from elite research universities to minor undergraduate colleges. As expected, faculty members at research universities publish the most, followed by those at elite 4-year schools and other doctoral institutions. Institutional prestige has little effect on productivity, except that elite universities employ a greater proportion of truly eminent scholars than other schools do. The fact that many of these scholars are hired by elite schools after achieving eminence elsewhere suggests that financial prowess, rather than institutional climate, produces the latter effect. Academics at all of these types of schools tend to continue publishing throughout their careers; achieving tenure has little effect on their subsequent scholarship. Faculty members at master's universities and lesser 4 year schools publish less than others and tend to cease publication activity after about 10 years, presumably upon receiving tenure. Males tend to publish more than females during the initial push for tenure, but not thereafter; females, unlike males, tend to increase their publication rates as they mature professionally. A subset of highly productive males who are moving toward more prestigious types of schools accounts for much of the remaininggender difference. The number of predoctoral publications is a relatively weak predictor of postdoctoral scholarship. PMID- 26151800 TI - Domain Denigration and Process Preference in Academic Psychology. AB - Unlike most other disciplines, psychology parses its field primarily in terms of processes or mental entities (e.g., learning, sensation, perception, memory), rather than domains of life (e.g., eating, work, leisure). Although there are merits in this organization, a perhaps unintended result is that psychology has paid minimal attention to the major domains of life and how people function in them. Examination of contemporary major introductory, social, and developmental psychology textbooks reveals that their indexes include almost no terms representing five critical domains: food, politics, religion, leisure entertainment, and work. The process division of psychology dates back at least to Wundt and James, and probably derives from psychology's origins and early dedication to discovering general laws of the mind. The avoidance of study of life domains in psychology is related to several forces, including a downgrading of both applied research and descriptive research in favor of theory and laboratory experimentation. Psychology would profit from paying greater attention to describing and explaining what people actually do, an endeavor that would perhaps be facilitated by a focus on the domains of daily life. PMID- 26151801 TI - Giving and Receiving Awards. AB - Awards in the form of orders, medals, decorations, prizes, and titles are ubiquitous in monarchies and republics, private organizations, and not-for-profit and profit-oriented firms. Nevertheless, this kind of nonmaterial extrinsic incentive has been given little attention in the social sciences, including psychology. The demand for awards relies on an individual's desire for distinction, and the supply of awards is governed by the desire to motivate. The technique of analytic narratives is used to show that a number of empirically testable propositions about awards are consistent with observable data. PMID- 26151802 TI - Giving Psychology Away: A Personal Journey. AB - In this autobiographical essay, I trace the origins of my passion for communicating with the public about mental health and the behavioral sciences and make a case for spreading such passion among psychologists. I also describe the circuitous route that led to my unlikely 4-year tenure as editor-in-chief of Psychology Today magazine and describe some of the inner workings of this New York-based, commercial enterprise-formerly the property of the American Psychological Association. I made some progress in that role to return the magazine to its scientific origins, providing an outlet for hundreds of scientists and practitioners to speak directly to millions of Americans about their work. This is an essential task, I argue, if our field is to flourish. I also detail my departure as editor-in-chief of Psychology Today and describe the magazine's rapid return to "pop" status. Media sources do not automatically welcome participation by clinicians or behavioral scientists. Through a contingency analysis, I suggest ways of improving our ability to interface successfully with media professionals. PMID- 26151803 TI - Volume 1, 2006. PMID- 26151804 TI - Millon's Evolutionary Model of Personality Assessment: A Case for Categorical/Dimensional Prototypes. AB - Theodore Millon (1928-2014) was arguably one of the most influential figures in conceptualizing and detailing personality styles and disorders in the latter 20th and early 21st centuries. A prominent member of the Axis II Work Group of DSM III, III-R, and IV, Millon continued refining his evolutionary model long after his active involvement with these committees, and remained focused on the future of personality assessment until his death in 2014. This article is an exploration of his latter works, critiques of recent DSM-5 developments, and commentary on the usefulness of his deductive methodology as it continues to apply to the study, classification, and clinical application of personality assessment. PMID- 26151805 TI - In-vivo phase contrast magnetic resonance angiography of the cerebrovascular system: a comparative study with duplex sonography. AB - PURPOSE: Assessment of the cerebral blood flow (CBF) is crucial in the evaluation of patients with steno-occlusive diseases of the arteries supplying the brain for prediction of stroke risk. Quantitative phase contrast magnetic resonance angiography (PC-MRA) can be utilised for noninvasive quantification of CBF. The aim of this study was to validate in-vivo PC-MRA data by comparing them with colour-coded duplex (CCD) sonography in patients with cerebrovascular disease. METHODS AND MATERIALS: We examined 24 consecutive patients (mean age 63 years) with stenosis of arteries supplying the brain using PC-MRA and CCD. Velocities were measured in a total of 209 stenotic and healthy arterial segments (110 extra and 99 intracranial). RESULTS: Moderate to good correlation of velocity measurements between both techniques was observed in all six extracranial and five out of seven intracranial segments (p <0.05). Velocities measured with CCD sonography were generally higher than those obtained by PC-MRA. Reversal of flow direction was detected consistently with both methods. CONCLUSION: PC-MRA represents a robust, standardised magnetic resonance imaging technique for blood flow measurements within a reasonable acquisition time, potentially evolving as valuable work-up tool for more precise patient stratification for revascularisation therapy. PC-MRA overcomes relevant weaknesses of CCD in being not operator-dependent and not relying on a bone window to assess the intracranial arteries. PMID- 26151806 TI - A systematic review of literature on psychosocial aspects of gynecomastia in adolescents and young men. AB - Gynecomastia represents a serious psychosocial challenge for many adolescent and young adult males, but short of surgery, little attention has been given to this concern. The purpose of this paper is to report findings from a systematic review of the literature about psychosocial correlates, psychosocial interventions, and quality of research evidence about young males with gynecomastia. From an initial 233 published papers, 10 studies were identified and reviewed. Five were descriptive case studies and included no statistical analyses. The other studies were all conducted with small samples. Despite the limited evidence, findings suggest that many young men suffer emotional distress concerning gynecomastia, but this distress has received few interventions beyond surgical removal of the breast tissue. Future studies are needed to address this problem more fully so that more aggressive measures such as frequent assessments of the physical and psychosocial aspects of the condition can be done by healthcare professionals. PMID- 26151807 TI - A review of research on smoking behavior in three demographic groups of veterans: women, racial/ethnic minorities, and sexual orientation minorities. AB - BACKGROUND: Veterans comprise a large segment of the U.S. population and smoke at high rates. One significant way to reduce healthcare costs and improve the health of veterans is to reduce smoking-related illnesses for smokers who have high smoking rates and/or face disproportionate smoking consequences (e.g. women, racial/ethnic minorities, sexual orientation minorities). OBJECTIVES: We reviewed published studies of smoking behavior in three demographic subgroups of veterans women, racial/ethnic minorities, and sexual orientation minorities - to synthesize current knowledge and identify areas in need of more research. METHODS: A MEDLINE search identified papers on smoking and veterans published through 31 December 2014. RESULTS: Twenty-five studies were identified that focused on gender (n = 17), race/ethnicity (n = 6), or sexual orientation (n = 2). Female and sexual orientation minority veterans reported higher rates of smoking than non-veteran women and sexual orientation majority veterans, respectively. Veterans appeared to be offered VA smoking cessation services equally by gender and race. Few studies examined smoking behavior by race/ethnicity or sexual orientation. Little information was identified examining the outcomes of specific smoking treatments for any group. CONCLUSION: There is a need for more research on all aspects of smoking and quit behavior for women, racial/ethnic minorities, and sexual orientation minority veterans. The high rates of smoking by these groups of veterans suggest that they may benefit from motivational interventions aimed at increasing quit attempts and longer and more intense treatments to maximize outcomes. Learning more about these veterans can help reduce costs for those who experience greater consequences of smoking. PMID- 26151808 TI - Technology delivered self-monitoring application to promote successful inclusion of an elementary student with autism. AB - The ever-increasing prevalence of children diagnosed with autism spectrum disorder (ASD) is paralleled in public educational settings, including general education classrooms. Challenges with social/behavioral functioning, including limited self-management and behavior inhibition, can lead to off-task and disruptive behaviors that interfere with acquisition of academic and social skills. Without effective and efficient interventions, opportunities to participate in inclusive settings will likely be reduced. Self-monitoring (SM) is an intervention with strong evidence for increasing prosocial behaviors and decreasing challenging behaviors for students with ASD in educational settings, although the cuing mechanisms (e.g., timers, stopwatch) and tracking materials (e.g., paper, pencil) can be cumbersome and obtrusive. I-Connect is an SM application that allows for customizable prompts, recording, and data monitoring. The purpose of this study was to evaluate, utilizing an ABAB design, the functional relationship between implementation of I-Connect SM intervention and increases in on-task behavior with concurrent decreases in disruptive behavior for an elementary student with ASD in a general education classroom. Results indicate an immediate increase in on-task behavior as well as a decrease in disruptive behaviors with each introduction of I-Connect. Implications for practice and future research are discussed. PMID- 26151809 TI - Morphological Evolution of Gyroid-Forming Block Copolymer Thin Films with Varying Solvent Evaporation Rate. AB - In this study, we aim to examine the morphological evolution of block copolymer (BCP) nanostructured thin films through solvent evaporation at different rates for solvent swollen polystyrene-block-poly(l-lactide) (PS-PLLA). Interesting phase transitions from disorder to perpendicular cylinder and then gyroid can be found while using a partially selective solvent for PS to swell PS-PLLA thin film followed by solvent evaporation. During the transitions, gyroid-forming BCP thin film with characteristic crystallographic planes of (111)G, (110)G, and (211)G parallel to air surface can be observed, and will gradually transform into coexisting (110)G and (211)G planes, and finally transforms to (211)G plane due to the preferential segregation of constituted block to the surface (i.e., the thermodynamic origin for self-assembly) that affects the relative amount of each component at the air surface. With the decrease on the evaporation rate, the disorder phase will transform to parallel cylinder and then directly to (211)G without transition to perpendicular cylinder phase. Most importantly, the morphological evolution of PS-PLLA thin films is strongly dependent upon the solvent removal rate only in the initial stage of the evaporation process due to the anisotropy of cylinder structure. Once the morphology is transformed back to the isotropic gyroid structure after long evaporation, the morphological evolution will only relate to the variation of the surface composition. Similar phase transitions at the substrate can also be obtained by controlling the ratio of PLLA-OH to PS-OH homopolymers to functionalize the substrate. As a result, the fabrication of well-defined nanostructured thin films with controlled orientation can be achieved by simple swelling and deswelling with controlled evaporation rate. PMID- 26151810 TI - Spin-Valve Effect in NiFe/MoS2/NiFe Junctions. AB - Two-dimensional (2D) layered transition metal dichalcogenides (TMDs) have been recently proposed as appealing candidate materials for spintronic applications owing to their distinctive atomic crystal structure and exotic physical properties arising from the large bonding anisotropy. Here we introduce the first MoS2-based spin-valves that employ monolayer MoS2 as the nonmagnetic spacer. In contrast with what is expected from the semiconducting band-structure of MoS2, the vertically sandwiched-MoS2 layers exhibit metallic behavior. This originates from their strong hybridization with the Ni and Fe atoms of the Permalloy (Py) electrode. The spin-valve effect is observed up to 240 K, with the highest magnetoresistance (MR) up to 0.73% at low temperatures. The experimental work is accompanied by the first principle electron transport calculations, which reveal an MR of ~9% for an ideal Py/MoS2/Py junction. Our results clearly identify TMDs as a promising spacer compound in magnetic tunnel junctions and may open a new avenue for the TMDs-based spintronic applications. PMID- 26151811 TI - Introducing the Review Manuscript Type. PMID- 26151812 TI - Hypoxia promotes the proliferation of MC3T3-E1 cells via the hypoxia-inducible factor-1alpha signaling pathway. AB - Investigations into the role of hypoxia have concentrated on hypoxic damage to cells and the associated adaptative mechanisms, however, the effects of hypoxia on cell proliferation and differentiation have received less attention. The present study aimed to investigate the role of hypoxia on the proliferation of MC3T3-E1 cells and examine the molecular mechanism involved. Cells treated with low levels of hypoxia had an increased percentage of S phase cells and a decreased percentage of G1 phase cells, promoted the level of cell proliferation associated proteins, proliferating cell nuclear antigen and cyclin D. In addition, hypoxia increased cell proliferation by upregulating the expression of hypoxia-inducible factor (HIF)-1alpha. The phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways augmented the expression of HIF-1alpha in the MC3T3-E1 cells. The present study demonstrated that hypoxia induces positive effects on osteoblast proliferation, suggesting a novel strategy in the treatment of osteoporosis. PMID- 26151813 TI - Land use as an explanatory factor for potential phosphorus loss risk, assessed by P indices and their governing parameters. AB - The total level of phosphorus (P) and the distribution of P pools in the topsoil are significantly affected by the excessive application of mineral and organic fertilizers connected with intensive agriculture. This leads to an increased potential risk for P loss, and then contributes to freshwater eutrophication. Soil test P (STP), P sorption index (PSI) and degree of P saturation (DPS) are commonly applied as proxies for assessing the risk of P loss. Although conceptually based, the empirical relationships between these operationally defined proxies and the actual P flux exhibit large spatial variations. Herein, a comprehensive synoptic study and monitoring of soil has been conducted in a watershed in north-eastern China. A set of conventional indicators for soil P loss risk were measured along with the main P pools, P sorption indices, texture, organic matter, as well as Fe and Al oxides and other mineral compositions. Moreover, detailed soil P speciation was conducted using phosphorus nuclear magnetic resonance ((31)P NMR) spectroscopy. In addition, phosphatase activities in the soils were determined for each land use soil category. The results reflected that the soil content of total P, total inorganic P and STP increased significantly following the order of increasing management intensity. STP, being strongly coupled to the application of P fertilizers, was a strong explanatory factor for the spatial differences in DPS - both between and within different land uses. The dominant inorganic and organic P species in the soils were orthophosphate and monoester-P, respectively. Their contents were oppositely correlated with the degree of management influence, with the amount of orthophosphate positively related. Alkaline phosphomonoesterase (AlP) represented the highest activities among the four representative phosphatases, i.e. enzymes that hydrolyze organic P - releasing labile orthophosphate. Orchard soils were found to contain the highest levels of monoester P as well as high AlP activities. This indicates a strong capacity to produce labile orthophosphate. Our results suggest that the type of land use can be employed as a general explanatory factor for considering the potential high risk of loss of P. Regionalized P loss parameters will further improve the accuracy of risk assessment. PMID- 26151814 TI - New insight on optical and magnetic Fe3O4 nanoclusters promising for near infrared theranostic applications. AB - Extensive efforts have been devoted to the development of a new biophotonic system using near infrared (NIR) nano-agents for non-invasive cancer diagnosis and therapy. Here, we developed a simple synthesis reaction of ligands, hydrazine, and iron(ii) chloride to fabricate Fe3O4 cluster-structured nanoparticles (CNPs) with interesting NIR photonics and high magnetization (Ms: 98.3 emu g(-1) and proton relaxivity r2: 234.6 mM(-1) s(-1)). These Fe3O4 CNPs exhibited optical absorption and reflection over all wavelengths, showing a U shape absorption band with a low absorbance at a range of 750-950 nm and a progressive evolution in the second near infrared region. Strengthening of the scattering effect by incubating Fe3O4 CNPs with HeLa cells was observed when optical contrast enhancement was performed in an optical coherence tomography (OCT) microscope system with a laser light source at 860 nm. Using a 1064 nm laser at a low power density (380 mW cm(-2)) to excite the Fe3O4 CNPs (375 ppm[Fe]) led to a rise in the water temperature from 25 degrees C to 58 degrees C within 10 min. Finally, we present the first example of magnetomotive OCT cellular imaging combined with enhanced photothermal therapy using Fe3O4 CNPs and applying a magnetic field, which is promising for preclinical and clinical trials in the future. PMID- 26151815 TI - Quercetin inhibits the mTORC1/p70S6K signaling-mediated renal tubular epithelial mesenchymal transition and renal fibrosis in diabetic nephropathy. AB - Quercetin is a classic flavonoid that inhibits the epithelial-mesenchymal transition (EMT) of tumor cells. However, the effects of quercetin on the EMT of renal tubular epithelial cells, a potential mechanism of renal fibrosis and important characteristic of diabetic nephropathy (DN), remain largely unknown. In the present study, we investigated the effects of quercetin on the EMT of two lines of renal tubular proximal epithelial cells (HK-2 and NRK-52E) induced with high glucose and renal fibrosis resulting from type 1 diabetes and tried to clarify the specific mechanisms underlying these effects. The in vitro results showed that the EMT of HK-2 and NRK-52E cells was induced by high glucose, and mTORC1/p70S6K was highly activated in these two cell lines cultured under high glucose. Quercetin effectively ameliorated the high glucose-induced EMT of HK-2 and NRK-52E cells and inhibited the activation of mTORC1/p70S6K. In vivo, diabetic rats showed a significant decline in renal function and severe renal fibrosis at 14 weeks after STZ injection. Furthermore, mTORC1/p70S6K was activated in the renal cortex of diabetic rats. Treatment with quercetin alleviated the decline in renal function, and the progression of renal fibrosis and inhibited mTORC1/p70S6K activation in the diabetic renal cortex. In addition, we examined the protein and mRNA levels of four transcriptional factors (snail, slug, twist and ZEB-1), which regulate E-cadherin expression at the transcriptional level both in vivo and in vitro. The results revealed that the elevated expression of snail and twist in HK-2 and NRK-52E cells cultured under high glucose and in the renal cortex of diabetic rats was inhibited by quercetin. These results demonstrated that quercetin ameliorates the EMT of HK-2 and NRK-52E cells induced by high glucose and renal fibrosis induced by diabetes, and these effects have been associated with the inhibition of the two transcriptional factors (snail and twist) and the activation of mTORC1/p70S6K. PMID- 26151816 TI - Alterations in Activation, Cytotoxic Capacity and Trafficking Profile of Peripheral CD8 T Cells in Young Adult Binge Drinkers. AB - BACKGROUND: Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity. AIM: To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern. METHODS: 55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their reported alcohol consumption pattern. Blood samples were obtained and hematic biometry and liver enzyme analysis were performed. Peripheral CD8 profile was established by expression of Granzyme B (GB), CD137, CD127, CD69, TLR4, PD1, CCR2, CCR4, CCR5 and CXCR4 by FACS. Data was analyzed by ANOVA, posthoc DMS and Tamhane, and principal component analysis (PCA) with varimax rotation, p<0.05. RESULTS: The Binge drinking group showed increased gammaGT together with increased expression of CD69 and reduced expression of TLR4, PD1, CCR2 and CXCR4 in peripheral CD8 cells. Other parameters were also specific to Binge drinkers. PCA established 3 factors associated with alcohol consumption: "Early Activation" represented by CD69 and TLR4 expression in the CD8 population; "Effector Activation" by CD69 expression in CD8 CD127(+)CD137(+) and CD8 CD25(+) CD137(+); and Trafficking by CXCR4 expression on total CD8 and CD8 GB(+)CXCR4(+), and CCR2 expression on total CD8. Binge drinking pattern showed low expression of Early Activation and Trafficking factors while Light drinking pattern exhibited high expression of Effector Activation factor. CONCLUSIONS: Alcohol consumption affects the immune phenotype of CD8 cells since binge drinking pattern was found to be associated with high CD69 and low TLR4, CXCR4 and CCR2 expression, which suggest recent activation, decreased sensitivity to LPS and lower migration capacity in response to chemokines SDF-1 and MCP-1. These results indicate that a binge-drinking pattern of alcohol consumption may induce an altered immune profile that could be related with liver damage and the increased susceptibility to infection reported to this behavior. PMID- 26151817 TI - Orthogonal Morphological Feature Size and Density Gradients for Exploring Synergistic Effects in Biology. AB - Gradient surfaces enable rapid screening and high-throughput investigations in various fields, such as biology and tribology. A new method is described for the preparation of material-independent morphological gradients, in which the density and height of roughness features are varied along two orthogonal axes. A polystyrene-particle-density gradient was produced by a dip-coating process on titanium-oxide-coated silicon wafers. A controlled exposure to ultraviolet light enabled the generation of a particle-height gradient in the orthogonal direction. These gradients were replicated to generate material-independent morphology gradients. MC3T3 cell proliferation studies were performed on titanium-coated replicas and showed a higher cell density on the high-feature-density region of the gradient. The cell area coverage was found to increase with decreasing particle height. PMID- 26151818 TI - Effect of Expressive Writing Intervention on Health Outcomes in Breast Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Numerous randomized controlled trials (RCTs) have arrived at conflicting conclusions on expressive writing (EW) as an intervention for breast cancer (BC) patients, but there has been no meta-analysis of these studies to assess the effectiveness of EW in BC population. METHODS: PubMed, Web of Science, The Cochrane Library, EMBASE, and CINAHL and the www.clinicaltrial.gov database on ongoing clinical trials were searched to identify all the RCTs investigating efficacy of EW on the physical and psychological health in BC patients. The risk of bias of the original studies was assessed using the Cochrane Collaboration's tool. Our primary outcomes for physical and psychological health were respectively negative somatic symptoms and negative mood which were stratified by emotional, benefit-finding and multiple prompts in sub-group analyses. The data were analyzed using Review Manager 5.2 and Stata version 12.0 statistical software. RESULTS: Of the 5,232 titles screened, we identified 11 RCTs with a total of 1,178 participants. The pooled results showed a significant effect of EW using either an emotional prompt or a benefit-finding prompt on reducing negative somatic symptoms in BC patients in the <=3-month follow-up group [Mean Difference (MD), -13.03, 95% CI, -19.23 to -6.83, P<0.0001; MD, -9.18, 95% CI, -15.57 to 2.79, P = 0.005]. There was no significant effect of EW on physical health in the >3-month follow-up group. There were no significant differences regarding psychological health indexes between EW intervention and control groups at any of the follow-up time-points (P>0.05). CONCLUSION: This systematic review and meta analysis reveals that EW intervention may have a significantly positive impact on the physical health but not the psychological health in BC patients, but this benefit may not last long. However, further high-quality studies with more homogeneity are needed to confirm the current findings. PMID- 26151820 TI - An insight into defect relaxation in metastable ZnO reflected by a unique luminescence and Raman evolutions. AB - Defects play a crucial role in semiconductors, but a facile method to observe defect variation inside semiconductors is still absent. Here, we provide an insight into defect relaxation in metastable ZnO nanoparticles, which are prepared via nonequilibrium laser ablation in liquid media, reflected by the Raman vibrations of surface optical (SO) and volume phonons, as well as by the evolution of luminescence. During the annealing process, the SO and volume phonon modes exhibit strong incompatibility and a unique "intermission" period in the temperature range from 300 degrees C to 400 degrees C, in which both the vibrations are completely suppressed in the Raman spectra. Combined with the corresponding defects-related photoluminescence spectra, it is demonstrated that there exists a delay between the reconstruction of the interfacial defects and annihilation of other intrinsic defects, including interstitial zinc and oxygen vacancy in the relaxation process, and that the sequence of different defects of ZnO in the order of instability is interfacial defect, interstitial zinc, and then oxygen vacancy. Such defect relaxation will deepen our understanding of some of the properties of semiconducting nanomaterials, including luminescence, photocatalysis, electronic transport, sensing and others. PMID- 26151819 TI - Fast kinetics of calcium signaling and sensor design. AB - Fast calcium signaling is regulated by numerous calcium channels exhibiting high spatiotemporal profiles which are currently measured by fluorescent calcium sensors. There is still a strong need to improve the kinetics of genetically encoded calcium indicators (sensors) to capture calcium dynamics in the millisecond time frame. In this review, we summarize several major fast calcium signaling pathways and discuss the recent developments and application of genetically encoded calcium indicators to detect these pathways. A new class of genetically encoded calcium indicators designed with site-directed mutagenesis on the surface of beta-barrel fluorescent proteins to form a pentagonal bipyramidal like calcium binding domain dramatically accelerates calcium binding kinetics. Furthermore, novel genetically encoded calcium indicators with significantly increased fluorescent lifetime change are advantageous in deep-field imaging with high light-scattering and notable morphology change. PMID- 26151822 TI - Setting Priorities for Optimizing Vascular Access Decision Making--An International Survey of Patients and Clinicians. AB - BACKGROUND: Many decisions around vascular access for haemodialysis warrant a collaborative treatment decision-making process, involving both clinician and patient. Yet, patients' experiences in this regard have been suboptimal. Although clinical practice guidelines could facilitate collaborative decision making, they often focus on the clinicians' side of the process, while failing to address the patients' perspective. The objective of this study was to explore and compare kidney patients' and clinicians' views on what vascular access-related decisions deserved priority for developing guidelines that will contribute to optimizing collaborative decision making. METHODS: In the context of updating their vascular access guideline, European Renal Best Practice surveyed an international panel of 85 kidney patients, 687 nephrologists, 194 nurses, and 140 surgeons/radiologists. In an electronic questionnaire, respondents rated 42 vascular access-related topics on a 5-point Likert scale. Based on mean standardized ratings, we compared priority ratings between patients and each clinician group. RESULTS: Selection of access type and site, as well as prevention of access infections received top priority across all respondent groups. Patients generally assigned higher priority to decisions regarding managing adverse effects of arteriovenous access and patient involvement in care, while clinicians more often prioritized decisions around sustaining patients' access options, technical aspects of access creation, and optimizing fistula maturation and patency. CONCLUSION: Apart from identifying the most pressing knowledge gaps, our study provides pointers for developing guidelines that may improve healthcare professionals' understanding of when to involve patients along the vascular access pathway. PMID- 26151824 TI - Mean platelet volume and left ventricular geometry in patients with aortic valve stenosis. AB - BACKGROUND: Mean platelet volume (MPV) is a well-established marker of platelet activation. In the current study, we compared MPV between patients with aortic valve stenosis (AS) and control subjects. We also assessed the association between MPV and left ventricular geometry in patients with AS. METHODS AND RESULTS: The study population consisted of 75 patients with AS and 38 age- and sex-matched control subjects. In patients with AS, peak pressure gradient was 83.0 +/- 30.8 mm Hg. MPV was significantly larger in patients with AS than control subjects (10.57 +/- 1.05 fl versus 9.72 +/- 0.66 fl, p < 0.001). There was a significant association between peak pressure gradient and MPV in 75 patients with AS and 38 control subjects (r = 0.35, p < 0.001). Among the patients with AS, there were 12 patients with normal geometry, 10 patients with concentric remodeling, 14 patients with eccentric hypertrophy and 39 patients with concentric hypertrophy. There was no significant difference in MPV among the four groups. There was no significant association between MPV and LVM index. CONCLUSIONS: Our data suggested that MPV increased in patients with AS, but did not reflect left ventricular geometry. PMID- 26151823 TI - Spontaneous restoration of transplantation tolerance after acute rejection. AB - Transplantation is a cure for end-stage organ failure but, in the absence of pharmacological immunosuppression, allogeneic organs are acutely rejected. Such rejection invariably results in allosensitization and accelerated rejection of secondary donor-matched grafts. Transplantation tolerance can be induced in animals and a subset of humans, and enables long-term acceptance of allografts without maintenance immunosuppression. However, graft rejection can occur long after a state of transplantation tolerance has been acquired. When such an allograft is rejected, it has been assumed that the same rules of allosensitization apply as to non-tolerant hosts and that immunological tolerance is permanently lost. Using a mouse model of cardiac transplantation, we show that when Listeria monocytogenes infection precipitates acute rejection, thus abrogating transplantation tolerance, the donor-specific tolerant state re emerges, allowing spontaneous acceptance of a donor-matched second transplant. These data demonstrate a setting in which the memory of allograft tolerance dominates over the memory of transplant rejection. PMID- 26151825 TI - Left ventricular hypertrophy on long-term cardiovascular outcomes in patients with ST-elevation myocardial infarction. AB - BACKGROUND: Left ventricular hypertrophy (LVH) had been associated with increased adverse cardiovascular events in hypertensive patients. Prognostic significance of LVH in patients with ST-elevation myocardial infarction (STEMI) is not established. This study aimed to investigate prognostic impact of LVH on the patients with STEMI. METHODS: We analyzed the data and clinical outcomes of 30 day survivors with STEMI who underwent successful coronary intervention from 2003 to 2009. Definition of LVH was LV mass index (LVMI) >115 g/m(2) in male and >95 g/m(2) in female. Patients were classified into a LVH group and a non-LVH group. Occurrence of major adverse cardiovascular events (MACE; death, recurrent MI, target vessel revascularization (TVR)) within 5 years was evaluated. RESULTS: We enrolled 418 patients and mean follow-up duration was 43 +/- 17 months. Two hundred and fourteen patients (51%) had LVH. The survival of the patients with LVH was significantly worse than the patients without LVH (log-rank p = 0.024). In a multivariate regression model, the presence of LVH was independently associated with increased risk for all-cause mortality (OR, 2.37; 95% CI, 1.096 5.123, p = 0.028). When the end points were analyzed based on LVH severity, all cause mortality was significantly correlated with LVH severity (p = 0.011). The severe LVH was independently associated with increased risk for all-cause mortality (OR, 5.110; 95% CI, 1.454-17.9, p = 0.001). CONCLUSION: LVH was associated with increased rate of adverse clinical outcomes in 30-day survivors after STEMI, who underwent successful coronary intervention. PMID- 26151826 TI - An evaluation of the effect of pentoxifylline on blood pressure and myocardial oxidative status following intake of western diet. AB - BACKGROUND: Western diet (WD) has been known to promote cardiac oxidative stress in models of hypertension and obesity. Pentoxifylline (PTX) is a potent antioxidant. The impact of PTX and WD on cardiac oxidative status in healthy hearts is unclear. AIM: we aimed to determine the impact of WD and/or PTX on blood pressure and myocardial oxidative status in normal rat hearts. METHOD: Young adult Sprague Dawley rats were randomly assigned into four groups; conventional diet (control), WD, PTX, or simultaneous combination of WD + PTX for 10 weeks. Blood pressure, lipids levels, and cardiac levels of oxidants and antioxidants were measured. RESULT: WD was associated with an increase in triglyceride level and a mild increase in systolic blood pressure (SBP), whereas PTX reduced SBP. Relative to control, no changes were observed in levels of TNF alpha and glutathione (GSH) system, however, a significant decrease in thiobarbituric acid reactive substances (TBARS) level was observed in all groups with a parallel increase in catalase activities. Superoxide dismutase and catalase activities were increased in the PTX group. Relative to the WD group, the WD + PTX group was associated with a significant increase in the activities of GSH peroxidase and reductase. CONCLUSIONS: The decrease in TBARS levels and the increase in catalase activities suggest that normal hearts adapt compensatory mechanisms to prevent oxidative damage in response to the mild increase in SBP associated with WD. Use of PTX with WD further enhanced antioxidant activities probably to balance the potential increase in reactive oxygen species. PMID- 26151821 TI - Genome-wide association study of colorectal cancer identifies six new susceptibility loci. AB - Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies. PMID- 26151827 TI - Conditional knockout of collecting duct bradykinin B2 receptors exacerbates angiotensin II-induced hypertension during high salt intake. AB - We elucidated the role of collecting duct kinin B2 receptor (B2R) in the development of salt-sensitivity and angiotensin II (ANG II)-induced hypertension. To this end, we used a Cre-Lox recombination strategy to generate mice lacking Bdkrb2 gene for B2R in the collecting duct (Hoxb7-Cre(tg/+):Bdkrb2(flox/flox)). In 3 groups of control (Bdkrb2(flox/flox)) and 3 groups of UB(Bdkrb2-/-) mice, systolic blood pressure (SBP) responses to high salt intake (4 or 8% NaCl; HS) were monitored by radiotelemetry in comparison with standard salt diet (0.4% NaCl) prior to and during subcutaneous ANG II infusion (1000 ng/min/kg) via osmotic minipumps. High salt intakes alone for 2 weeks did not alter SBP in either strain. ANG II significantly increased SBP equally in control (121 +/- 2 to 156 +/- 3 mmHg) and UB(Bdkrb2-/-) mice (120 +/- 2 to 153 +/- 2 mmHg). The development of ANG II-induced hypertension was exacerbated by 4%HS in both control (125 +/- 3 to 164 +/- 5 mmHg) and UB(Bdkrb2-/-) mice (124 +/- 2 to 162 +/ 3 mmHg) during 2 weeks. Interestingly, 8%HS caused a more profound and earlier ANG II-induced hypertension in UB(Bdkrb2-/-) (129 +/- 2 to 166 +/- 3 mmHg) as compared to control (128 +/- 2 to 158 +/- 2 mmHg) and it was accompanied by body weight loss and increased mortality. In conclusion, targeted inactivation of B2R in the renal collecting duct does not cause salt-sensitivity; however, collecting duct B2R attenuates the hypertensive actions of ANG II under conditions of very high salt intake. PMID- 26151828 TI - Practical Prediction of Ten Common Streptococcus pneumoniae Serotypes/Serogroups in One PCR Reaction by Multiplex Ligation-Dependent Probe Amplification and Melting Curve (MLPA-MC) Assay in Shenzhen, China. AB - BACKGROUND: Streptococcus pneumoniae has more than 95 distinct serotypes described to date. However, only certain serotypes are more likely to cause pneumococcal diseases. Thus serotype surveillance is important for vaccine formula design as well as in post-vaccine serotype shift monitor. The goal of this study was to develop a practical screening assay for ten Shenzhen China common pneumococcal serotypes/serogroups in one molecular reaction. METHODS: A molecular assay, based on multiplex ligation-dependent probe amplification (MLPA) and melting curve (MC) analysis, was developed in an integrated approach (MLPA MC) for the detection of ten capsular serotypes/serogroups 4, 6 (6A/6B/6C/6D), 9V/9A, 14, 15F/15A, 15B/15C, 18 (18F/18A/18B/18C), 19F, 19A and 23F. We designed serotype/serogroup-specific MLPA probes and fluorescent detection probes to discriminate the different serotypes/serogroups in one molecular reaction. The three steps of MLPA-MC assay are continuous reactions in one well detected by LightCycler 480. A total of 210 S. pneumoniae isolates from our local Maternity and Child Health Hospital were randomly chosen to evaluate the assay against published multiplex PCR assays. RESULTS: Our results showed that 198 (94.3%) of S. pneumoniae isolates were type-able by our assays and the results were in complete concordance with the published multiplex PCRs. Using the MLPA-MC assay, 96 S. pneumoniae isolates could be typed within 3 hours with limited hands-on time. This serotype/serogroup-screening assay can be easily modified or extended by modification of the serotype/serogroup-specific MLPA probes combinations according to the needs of different laboratories. CONCLUSIONS: We recommend use of this assay as a starting point for screening serotype/serogroup frequencies. There is a need for this assay to be combined with other molecular typing assays, like published serotype specific PCRs, or even the Quellung reaction for serotype confirmation. PMID- 26151829 TI - Nanopatterning of Magnetic CrNi Prussian Blue Nanoparticles Using a Bacterial S Layer as a Biotemplate. AB - We have developed a simple process to fabricate on a bioplatform patterns of nanoparticles of a molecule-based magnet. Nanoparticles of the ferromagnetic Prussian blue derivative CsxNi[Cr(CN)6] were orderly deposited onto S-layers of Lysinibacillus sphaericus, forming a dense carpet of nanoparticles following the square lattice (p4) pattern of the biotemplate. These results are encouraging to extend this approach by focusing on molecule-based magnets patterned into domains with controlled shapes and positions on a biosurface. PMID- 26151831 TI - Breast cancer diagnosis in digitized mammograms using curvelet moments. AB - BACKGROUND: Feature extraction is a key issue in designing a computer aided diagnosis system. Recent researches on breast cancer diagnosis have reported the effectiveness of multiscale transforms (wavelets and curvelets) for mammogram analysis and have shown the superiority of curvelet transform. However, the curse of dimensionality problem arises when using the curvelet coefficients and therefore a reduction method is required to extract a reduced set of discriminative features. METHODS: This paper deals with this problem and proposes a feature extraction method based on curvelet transform and moment theory for mammogram description. First, we performed discrete curvelet transform and we computed the four first-order moments from curvelet coefficients distribution. Hence, two feature sets can be obtained: moments from each band and moments from each level. In this work, both sets are studied. Then, the t-test ranking technique was applied to select the best features from each set. Finally, a k nearest neighbor classifier was used to distinguish between normal and abnormal breast tissues and to classify tumors as malignant or benign. Experiments were performed on 252 mammograms from the Mammographic Image Analysis Society (mini MIAS) database using the leave-one-out cross validation as well as on 11553 mammograms from the Digital Database for Screening Mammography (DDSM) database using 2*5-fold cross validation. RESULTS: Experimental results prove the effectiveness and the superiority of curvelet moments for mammogram analysis. Indeed, results on the mini-MIAS database show that curvelet moments yield an accuracy of 91.27% (resp. 81.35 %) with 10 (resp. 8) features for abnormality (resp. malignancy) detection. In addition, empirical comparisons of the proposed method against state-of-the-art curvelet-based methods on the DDSM database show that the suggested method does not only lead to a more reduced feature set, but it also statistically outperforms all the compared methods in terms of accuracy. CONCLUSIONS: In summary, curvelet moments are an efficient and effective way to extract a reduced set of discriminative features for breast cancer diagnosis. PMID- 26151830 TI - Targeted Sequencing Reveals Large-Scale Sequence Polymorphism in Maize Candidate Genes for Biomass Production and Composition. AB - A major goal of maize genomic research is to identify sequence polymorphisms responsible for phenotypic variation in traits of economic importance. Large scale detection of sequence variation is critical for linking genes, or genomic regions, to phenotypes. However, due to its size and complexity, it remains expensive to generate whole genome sequences of sufficient coverage for divergent maize lines, even with access to next generation sequencing (NGS) technology. Because methods involving reduction of genome complexity, such as genotyping-by sequencing (GBS), assess only a limited fraction of sequence variation, targeted sequencing of selected genomic loci offers an attractive alternative. We therefore designed a sequence capture assay to target 29 Mb genomic regions and surveyed a total of 4,648 genes possibly affecting biomass production in 21 diverse inbred maize lines (7 flints, 14 dents). Captured and enriched genomic DNA was sequenced using the 454 NGS platform to 19.6-fold average depth coverage, and a broad evaluation of read alignment and variant calling methods was performed to select optimal procedures for variant discovery. Sequence alignment with the B73 reference and de novo assembly identified 383,145 putative single nucleotide polymorphisms (SNPs), of which 42,685 were non-synonymous alterations and 7,139 caused frameshifts. Presence/absence variation (PAV) of genes was also detected. We found that substantial sequence variation exists among genomic regions targeted in this study, which was particularly evident within coding regions. This diversification has the potential to broaden functional diversity and generate phenotypic variation that may lead to new adaptations and the modification of important agronomic traits. Further, annotated SNPs identified here will serve as useful genetic tools and as candidates in searches for phenotype-altering DNA variation. In summary, we demonstrated that sequencing of captured DNA is a powerful approach for variant discovery in maize genes. PMID- 26151832 TI - Time-Resolved Electron Paramagnetic Resonance Study of Photoinduced Electron Transfer in Pd Porphyrin-Quinone and Zn Porphyrin-Quinone Dyads with a Cyclohexylene Spacer. AB - Peculiarities of the light induced intramolecular electron transfer processes in two ensembles where Pd porphyrin and Zn porphyrin donors with similar peripheral substituents are covalently linked via cyclohexylene spacer with a quinone acceptor, were studied by time-resolved electron paramagnetic resonance spectroscopy in different phases of the magnetically oriented nematic liquid crystal E-7. In the photoexcited PdP-Q the net absorptive signal was observed and ascribed to the thermally equilibrated spectrum of (3)*(PdP(*+)-Q(*-)). In ZnP-Q photoinduced intramolecular electron transfer was also found. It was demonstrated that the multiplet spectrum of the charge-separated state (3)*(ZnP(*+)-Q(*-)) consists of two signals with different widths and decay times. The signals were assigned to two spin-polarized triplets of the radical pairs formed in "stretched" and "folded" ensemble conformers, corresponding to different configurations of the cyclohexylene spacer. These findings were discussed in terms of differences in the properties of the porphyrin metal cores, macrocycle peripheral substituents and geometry of the donor-acceptor cyclohexylene spacer. PMID- 26151833 TI - Improved Power Conversion Efficiency of Inverted Organic Solar Cells by Incorporating Au Nanorods into Active Layer. AB - This Research Article describes a cooperative plasmonic effect on improving the performance of organic solar cells. When Au nanorods(NRs) are incorporated into the active layers, the designed project shows superior enhanced light absorption behavior comparing with control devices, which leads to the realization of organic solar cell with power conversion efficiency of 6.83%, accounting for 18.9% improvement. Further investigations unravel the influence of plasmonic nanostructures on light trapping, exciton generation, dissociation, and charge recombination and transport inside the thin films devices. Moreover, the introduction of high-conductivity Au NRs improves electrical conductivity of the whole device, which contributes to the enhanced fill factor. PMID- 26151834 TI - Hsp90 oligomerization process: How can p23 drive the chaperone machineries? AB - The 90-kDa heat shock protein (Hsp90) is a highly flexible dimer that is able to self-associate in the presence of divalent cations or under heat shock. In a previous work, we focused on the Mg2+-induced oligomerization process of Hsp90, and characterized the oligomers. Combining analytical ultracentrifugation, size exclusion chromatography coupled to multi-angle laser light scattering and high mass matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we studied the interaction of p23 with both Hsp90 dimer and oligomers. Even if p23 predominantly binds the Hsp90 dimer, we demonstrated, for the first time, that p23 is also able to interact with Hsp90 oligomers, shifting the Hsp90 dimer-oligomers equilibrium toward dimer. Our results showed that the Hsp90:p23 binding stoichiometry decreases with the Hsp90 oligomerization degree. Therefore, we propose a model in which p23 would act as a "protein wedge" regarding the Hsp90 dimer closure and the Hsp90 oligomerization process. PMID- 26151835 TI - Pediatric sand aspiration managed using bronchoscopy and extracorporeal membrane oxygenation. AB - Sand aspiration is a rare but potentially fatal occurrence to consider in near drownings, accidental burials or cave-ins. Optimal management is not well defined. PMID- 26151836 TI - Acute exacerbation of idiopathic pulmonary fibrosis. PMID- 26151837 TI - Holocellulose Nanofibers of High Molar Mass and Small Diameter for High-Strength Nanopaper. AB - Wood cellulose nanofibers (CNFs) based on bleached pulp are different from the cellulose microfibrils in the plant cell wall in terms of larger diameter, lower cellulose molar mass, and modified cellulose topochemistry. Also, CNF isolation often requires high-energy mechanical disintegration. Here, a new type of CNFs is reported based on a mild peracetic acid delignification process for spruce and aspen fibers, followed by low-energy mechanical disintegration. Resulting CNFs are characterized with respect to geometry (AFM, TEM), molar mass (SEC), and polysaccharide composition. Cellulose nanopaper films are prepared by filtration and characterized by UV-vis spectrometry for optical transparency and uniaxial tensile tests. These CNFs are unique in terms of high molar mass and cellulose hemicellulose core-shell structure. Furthermore, the corresponding nanopaper structures exhibit exceptionally high optical transparency and the highest mechanical properties reported for comparable CNF nanopaper structures. PMID- 26151838 TI - Glucocorticoids can affect Pseudomonas aeruginosa (ATCC 27853) internalization and intracellular calcium concentration in cystic fibrosis bronchial epithelial cells. AB - BACKGROUND AND OBJECTIVE: Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated. METHODS: We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide. RESULTS: GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration. CONCLUSION: These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out. PMID- 26151839 TI - Carvacrol protects against spinal cord injury in rats via suppressing oxidative stress and the endothelial nitric oxide synthase pathway. AB - Carvacrol (CAR) is a naturally occurring phenolic monoterpene and has been demonstrated to possess a spectrum of pharmacological actions. The present study was designed to assess the neuroprotection of CAR against spinal cord injury (SCI) in rats and to identify the underlying mechanisms. SCI was induced using the modified weight-drop method in Wistar rats. CAR or saline was administered at doses of 25, 50 and 100 mg/kg for 46 days. Neuronal function following SCI was evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Spinal cord edema was assessed by measuring the water content in spinal cord tissues. The oxidative indicators, including malondialdehyde, catalase, superoxide dismutase glutathione peroxidase and 8-isoprotane as well as endothelial nitric oxide synthase (eNOS) activity and caspase-3 were measured using corresponding commercial kits. The protein expression of eNOS and B cell lymphoma-2 (Bcl-2) as well as Bcl-2-associated X protein (Bax) was analyzed by western blot analysis. The SCI-induced rats demonstrated marked reductions in BBB scores. CAR treatment recovered neurological function with decreasing BBB scores. CAR was found to have inhibitory effects on the water content in the spinal cord, oxidative stress, eNOS, nitric oxide production and apoptosis-associated molecules, including Bax and caspase-3 as well as promoting Bcl-2 expression in SCI-induced rats. These results suggested that CAR protects against SCI via mediating oxidative stress and the eNOS signaling pathway. PMID- 26151840 TI - Parallel reconstruction in accelerated multivoxel MR spectroscopy. AB - PURPOSE: To develop the simultaneous acquisition of multiple voxels in localized MR spectroscopy (MRS) using sensitivity encoding, allowing reduced total scan time compared to conventional sequential single voxel (SV) acquisition methods. METHODS: Dual volume localization was used to simultaneously excite voxels in both hemispheres. Receiver coil sensitivity profiles were used to unfold the data. To demonstrate the method, MRS voxels in the left and right hippocampus were measured at 3 tesla (T) and the left and right motor cortices at 7T. Spectra were compared to conventional SV acquisitions. Spectra were also recorded from the lesion and contralateral hemisphere of a patient with a low-grade oligodendroglioma at 7T. RESULTS: It was possible to generate signal in two voxels simultaneously and separate the signal originating from the different locations, with spectral results almost identical to those observed using conventional single voxel methods. The method results in an increased chemical shift displacement artifact, which might be improved by advanced pulse designs, and a noise increase due to the unfolding g-factor, which was larger at 3T than 7T. CONCLUSION: The simultaneous acquisition of voxels for MRS is possible by using modulated slice-selective pulses and receive coil sensitivity profiles to unfold the resulting signals. PMID- 26151841 TI - Systematic review: cessation of long-term nucleos(t)ide analogue therapy in patients with hepatitis B e antigen-negative chronic hepatitis B. AB - BACKGROUND: It has been debated whether finite nucleos(t)ide analogue therapy is feasible in HBeAg-negative chronic hepatitis B. AIM: To review this issue systematically. METHODS: Using text terms HBsAg and various nucleos(t)ide analogues, PubMed was searched between 1995 and 2014 to find studies on therapy >6 months in adult HBeAg-negative chronic hepatitis B patients with off-therapy follow-up >6 months. RESULTS: Twenty-two studies with a total of 1732 patients were identified and included. The median duration of therapy, consolidation therapy and off-therapy follow-up ranged from 6 months to 8 years, 4 to 96 weeks and 6 to 80 months respectively. Patients were monitored with serum ALT and HBV DNA monthly in the first 1-3 months and every 3-6 months afterwards in most studies. The 1-year off-therapy 'virological relapse' (HBV DNA >2000 IU/mL) and 'clinical relapse' (HBV DNA > 2000 IU/mL + ALT elevation) occurred in <70% and <50% of the patients, respectively, and <40% of the patients received re treatment. These rates were higher in patients with shorter treatment, shorter consolidation therapy and those treated with less potent nucleos(t)ide analogues. Off-therapy severe flares were rare and hepatic decompensation was reported in only one patient with cirrhosis. Biochemical relapse reflecting enhanced immune mediated hepatocyte killing may lead to a higher chance for off-therapy HBsAg seroclearance and be possibly desirable. CONCLUSION: With an appropriate stopping rule and a proper off-therapy monitoring plan, cessation of long-term nucleos(t)ide analogue therapy prior to HBsAg seroclearance in HBeAg-negative chronic hepatitis B is a feasible alternative to indefinite treatment. PMID- 26151842 TI - Differences between Mice and Humans in Regulation and the Molecular Network of Collagen, Type III, Alpha-1 at the Gene Expression Level: Obstacles that Translational Research Must Overcome. AB - Collagen, type III, alpha-1 (COL3A1) is essential for normal collagen I fibrillogenesis in many organs. There are differences in phenotypes of mutations in the COL3A1 gene in humans and mutations in mice. In order to investigate whether the regulation and gene network of COL3A1 is the same in healthy populations of mice and humans, we compared the quantitative trait loci (QTL) that regulate the expression level of COL3A1 and the gene network of COL3A1 pathways between humans and mice using whole genome expression profiles. Our results showed that, for the regulation of expression of Col3a1 in mice, an eQTL on chromosome (Chr) 12 regulates the expression of Col3a1. However, expression of genes in the syntenic region on human Chr 7 has no association with the expression level of COL3A1. For the gene network comparison, we identified 44 top genes whose expression levels are strongly associated with that of Col3a1 in mice. We next identified 41 genes strongly associated with the expression level of COL3A1 in humans. There are a few but significant differences in the COL3A1 gene network between humans and mice. Several genes showed opposite association with expression of COL3A1. These genes are known to play important roles in development and function of the extracellular matrix of the lung. Difference in the molecular pathway of key genes in the COL3A1 gene network in humans and mice suggest caution should be used in extrapolating results from models of human lung diseases in mice to clinical lung diseases in humans. These differences may influence the efficacy of drugs in humans whose development employed mouse models. PMID- 26151844 TI - Retinal Cell Death Caused by Sodium Iodate Involves Multiple Caspase-Dependent and Caspase-Independent Cell-Death Pathways. AB - Herein, we have investigated retinal cell-death pathways in response to the retina toxin sodium iodate (NaIO3) both in vivo and in vitro. C57/BL6 mice were treated with a single intravenous injection of NaIO3 (35 mg/kg). Morphological changes in the retina post NaIO3 injection in comparison to untreated controls were assessed using electron microscopy. Cell death was determined by TdT mediated dUTP-biotin nick end labeling (TUNEL) staining. The activation of caspases and calpain was measured using immunohistochemistry. Additionally, cytotoxicity and apoptosis in retinal pigment epithelial (RPE) cells, primary retinal cells, and the cone photoreceptor (PRC) cell line 661W were assessed in vitro after NaIO3 treatment using the ApoToxGloTM assay. The 7-AAD/Annexin-V staining was performed and necrostatin (Nec-1) was administered to the NaIO3 treated cells to confirm the results. In vivo, degenerating RPE cells displayed a rounded shape and retracted microvilli, whereas PRCs featured apoptotic nuclei. Caspase and calpain activity was significantly upregulated in retinal sections and protein samples from NaIO3-treated animals. In vitro, NaIO3 induced necrosis in RPE cells and apoptosis in PRCs. Furthermore, Nec-1 significantly decreased NaIO3-induced RPE cell death, but had no rescue effect on treated PRCs. In summary, several different cell-death pathways are activated in retinal cells as a result of NaIO3. PMID- 26151843 TI - Intracellular Protein Shuttling: A Mechanism Relevant for Myelin Repair in Multiple Sclerosis? AB - A prominent feature of demyelinating diseases such as multiple sclerosis (MS) is the degeneration and loss of previously established functional myelin sheaths, which results in impaired signal propagation and axonal damage. However, at least in early disease stages, partial replacement of lost oligodendrocytes and thus remyelination occur as a result of resident oligodendroglial precursor cell (OPC) activation. These cells represent a widespread cell population within the adult central nervous system (CNS) that can differentiate into functional myelinating glial cells to restore axonal functions. Nevertheless, the spontaneous remyelination capacity in the adult CNS is inefficient because OPCs often fail to generate new oligodendrocytes due to the lack of stimulatory cues and the presence of inhibitory factors. Recent studies have provided evidence that regulated intracellular protein shuttling is functionally involved in oligodendroglial differentiation and remyelination activities. In this review we shed light on the role of the subcellular localization of differentiation associated factors within oligodendroglial cells and show that regulation of intracellular localization of regulatory factors represents a crucial process to modulate oligodendroglial maturation and myelin repair in the CNS. PMID- 26151845 TI - BubR1 Acts as a Promoter in Cellular Motility of Human Oral Squamous Cancer Cells through Regulating MMP-2 and MMP-9. AB - BubR1 is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubR1 was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC). However, the effect of BubR1 on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubR1 in the progression of OSCC and confirm the expression of BubR1 in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubR1 was markedly increased in four OSCC cell lines, Ca9-22, HSC3, SCC9 and Cal-27 cells, compared to two normal cells, normal human oral keratinocytes (HOK) and human gingival fibroblasts (HGF). Moreover, the expression of BubR1 in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubR1 was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubR1 knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. Consistently, the activities of metastasis-associated metalloproteinases MMP-2 and MMP-9 were attenuated in BubR1 knockdown Ca9-22 cells, suggesting the role of BubR1 in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubR1 could be a prognostic index in OSCC patients. PMID- 26151847 TI - A Multi-Objective Approach for Protein Structure Prediction Based on an Energy Model and Backbone Angle Preferences. AB - Protein structure prediction (PSP) is concerned with the prediction of protein tertiary structure from primary structure and is a challenging calculation problem. After decades of research effort, numerous solutions have been proposed for optimisation methods based on energy models. However, further investigation and improvement is still needed to increase the accuracy and similarity of structures. This study presents a novel backbone angle preference factor, which is one of the factors inducing protein folding. The proposed multiobjective optimisation approach simultaneously considers energy models and backbone angle preferences to solve the ab initio PSP. To prove the effectiveness of the multiobjective optimisation approach based on the energy models and backbone angle preferences, 75 amino acid sequences with lengths ranging from 22 to 88 amino acids were selected from the CB513 data set to be the benchmarks. The data sets were highly dissimilar, therefore indicating that they are meaningful. The experimental results showed that the root-mean-square deviation (RMSD) of the multiobjective optimization approach based on energy model and backbone angle preferences was superior to those of typical energy models, indicating that the proposed approach can facilitate the ab initio PSP. PMID- 26151846 TI - 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration. AB - Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP) cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo. PMID- 26151849 TI - Transcriptome Sequencing of Lima Bean (Phaseolus lunatus) to Identify Putative Positive Selection in Phaseolus and Legumes. AB - The identification of genes under positive selection is a central goal of evolutionary biology. Many legume species, including Phaseolus vulgaris (common bean) and Phaseolus lunatus (lima bean), have important ecological and economic value. In this study, we sequenced and assembled the transcriptome of one Phaseolus species, lima bean. A comparison with the genomes of six other legume species, including the common bean, Medicago, lotus, soybean, chickpea, and pigeonpea, revealed 15 and 4 orthologous groups with signatures of positive selection among the two Phaseolus species and among the seven legume species, respectively. Characterization of these positively selected genes using Non redundant (nr) annotation, gene ontology (GO) classification, GO term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these genes are mostly involved in thylakoids, photosynthesis and metabolism. This study identified genes that may be related to the divergence of the Phaseolus and legume species. These detected genes are particularly good candidates for subsequent functional studies. PMID- 26151850 TI - More Adventures in Photodynamic Therapy. AB - Photodynamic therapy is a procedure that can provide a selective eradication of neoplastic disease if sufficient drug, light, and oxygen are available. As this description suggests, it involves the photosensitization of malignant tissues to irradiation with photons in the visible range. While not suitable for tumors at unknown loci, it can be of use for eradication of cancer at surgical margins and therapy at sites where substantial surgery might otherwise be involved. Drug development has been delayed by several factors including the reluctance of major pharmaceutical firms in the United States to invest in this technology along with some unwise approaches in the past. PMID- 26151851 TI - Empirically Supported Interventions. AB - Within the past four decades the social work profession has responded to the challenge to base practice on empirical evidence to adequately meet client needs. Most social workers would agree that the challenge has resulted in positive changes in the majority of cases-for example, in the execution of relevant research studies; the incorporation of more research findings into practice; the development of a technology of interpersonal helping; an emphasis on the incorporation of new knowledge bases, such as socio-behavioral and systems theory, in the curricula of schools of social work; and the development of services to meet emerging client needs and evidence-based practice. In this article the authors outline different references available pertaining to empirically supported interventions. A literature review revealed several textbooks, reference resources, journals, and handbooks that contain the most current research on therapeutic interventions. Different treatment components were explored in an effort to uncover the most cutting-edge developments in psychosocial treatments. These treatment components include treatment configuration, worker traits, compatibility of worker and client characteristics, professionals versus paraprofessionals, treatment length, and behavior acquisition. PMID- 26151848 TI - Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE). AB - Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. Neuropsychiatric symptoms, particularly affective and cognitive indications, may be among the earliest manifestations of SLE. Among the potential pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction is evident before significant levels of autoantibody titers and nephritis are present. We examined the behavioral profile of MRL/lpr mice and their congenic controls, a comprehensive plasma cytokine and chemokine profile, and brain levels of serotonin and kynurenine pathway metabolites. Consistent with previous studies, MRL/lpr mice had increased depression-like behavior and visuospatial memory impairment. Plasma levels of different inflammatory molecules (Haptoglobin, interleukin 10 (IL-10), interferon gamma-inducible protein 10 (IP-10/CXCL10), lymphotactin, macrophage inhibitory protein 3beta (MIP-3beta/CCL19), monocyte chemotactic protein 1, 3 and 5 (MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12), vascular cell adhesion molecule 1 (VCAM-1), lymphotactin and interferon gamma (IFN-gamma)) were increased in MRL/lpr mice. In cortex and hippocampus, MRL/lpr mice had increased levels of kynurenine pathway metabolites (kynurenine, 3 hydroxykynurenine, 3-hydroxynthranilic acid and quinolinic acid). Therefore, our study suggests that increased cytokine expression may be critical in the regulation subtle aspects of brain function in NP-SLE via induction of IDO and tryptophan/kynurenine metabolism. PMID- 26151852 TI - Nitrate removal by organotrophic anaerobic ammonium oxidizing bacteria with C2/C3 fatty acid in upflow anaerobic sludge blanket reactors. AB - In anaerobic ammonium oxidation (Anammox) process, a harsh ratio of nitrite to ammonia in influent was demanded, and the max nitrogen removal efficiency could only achieve to 89%, both of which limited the development of Anammox. The aim of this work was to study the nitrate removal by organotrophic anaerobic ammonium oxidizing bacteria (AAOB) with C2/C3 fatty acid in upflow anaerobic sludge blanket (UASB) reactors. In this study, organotrophic AAOB was successfully enriched by adding acetate and propionate with the total organic carbon to nitrogen (TOC/N) ratio of 0.1. In the condition of low substrate, the TN removal efficiency reached 90%, with the effluent TN of around 11.8 mg L(-1). After the addition of acetate and propionate, the predominant species in Anammox granular sludge transformed to Candidatus Jettenia that belonging to organotrophic AAOB from the Candidatus Kuenenia relating to general AAOB. PMID- 26151853 TI - Effect of fillers on key characteristics of sludge thermophilic anaerobic digestion. AB - In anaerobic digestion (AD) of sludge, AD efficiency and digested sludge (DS) dewaterability are critical factors. In this study, polyester non-woven fabric fillers were integrated into a sludge digester. The effect of such fillers on digestion was investigated in thermophilic temperature range in semi-continuous mode. Methane production of filler system and control reactor were significantly different (P < 0.05, paired t-test). At hydraulic retention times of 18 days and 12 days, the corresponding methane yields from filler system were 140% and 161%, respectively, of the yields from control digester without filler. Improvement of DS dewaterability was uncertain during 110 days of operation. While after a longer period of digestion, filler system resulted in a lower normalized capillary suction time of DS (76.5 +/- 21.6 s L/g total suspended solids) than control reactor (118.7 +/- 32.9 s L/g total suspended solids). The results showed that the filler could improve thermophilic AD performance, except at too short hydraulic retention times. PMID- 26151854 TI - Performance of system consisting of vertical flow trickling filter and horizontal flow multi-soil-layering reactor for treatment of rural wastewater. AB - In order to improve nitrogen removal for rural wastewater, a novel two-stage hybrid system, consisting of a vertical flow trickling filter (VFTF) and a horizontal flow multi-soil-layering (HFMSL) bioreactor was developed. The performance of the apparatus was observed under various carbon-nitrogen ratios and water spraying frequencies separately. The maximum removal efficiency of total nitrogen (TN) for the hybrid system was 92.8% while the removal rates of CODCr, ammonium (NH4(+)-N), and total phosphorus (TP) were 94.1%, 96.1%, 92.0% respectively, and the corresponding effluent concentrations were 3.61, 21.20, 1.91, and 0.33 mg L(-1). The horizontal flow mode for MSL led the system to denitrifying satisfactorily as it ensured relatively long hydraulic retention time (HRT), ideal anoxic condition and adequate organic substrates supply. Also, higher water spraying frequency benefited intermittent feeding system for pollutants removal. Shock loading test indicated that the hybrid system could operate well even at hydraulic shock loadings. PMID- 26151855 TI - Exogenous capture of medial-frontal oscillatory mechanisms by unattended conflicting information. AB - A long-standing debate in psychology and cognitive neuroscience concerns the way in which unattended information is processed and influences goal-directed behavior. Although selective attention allows us to filter out task-irrelevant information, there is a substantial number of unattended, yet relevant, events that must be evaluated in a flexible manner so that appropriate behaviors can succeed. Here we inspected the extent to which unattended conflicting visual information, which cannot be consciously identified, influences behavior and activates medial prefrontal cortex (mPFC) mechanisms of action-monitoring and regulation, traditionally associated with conscious control processes. To that end, we performed two experiments using a novel variant of the Eriksen flanker task in which spatial attention was manipulated, preventing the conscious identification of unattended visual events. The first behavioral experiment was conducted to validate the efficacy of the novel paradigm. In the second experiment, we evaluated electrophysiological correlates of mPFC activity (a frontocentral negative ERP component and medial-frontal theta oscillations) in response to attended and unattended conflicting events. The results of both experiments demonstrated that attended and unattended conflicting stimuli altered subjects' behavior in a similar fashion, i.e. slowing down their reaction times and increasing their error rates. Importantly, the results of the EEG experiment showed that unattended conflicting stimuli, similarly to attended conflicting stimuli, led to an increase in theta-related frontocentral ERP activity and medial-frontal theta power, irrespective of the degree of conscious representation of the sources of conflict. This study provides evidence that medial-frontal theta oscillations represent a neural mechanism through which the mPFC may suppress and regulate potentially inappropriate actions that are automatically triggered by conflicting environmental stimuli to which we are oblivious. PMID- 26151856 TI - LC-MS2-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity. AB - Recently, phorbol esters from Euphorbiaceae have been shown to elicit potent and selective antiviral activity on the replication of Chikungunya virus (CHIKV) in cell culture. With the objective to found new compounds with anti-CHIKV activities, 45 extracts from various plant parts of 11 Mediterranean Euphorbia and one Mercurialis species were evaluated for selective inhibition of CHIKV replication. All EtOAc extracts, especially those prepared from latex, exhibited significant and selective antiviral activity in a Chikungunya virus-cell-based assay. An LC-MS(2) dereplication method was then developed to investigate whether known diterpenoids with anti-CHIKV activity, such as the potent anti-CHIKV 12-O tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-didecanoate, and prostratin as well as 24 other commercially available diterpenoids of tigliane-, ingenane-, and daphnane-type for which the anti-CHIKV activity have been established in advance (Nothias-Scaglia et al. 2015), were present in the Euphorbia extracts. Only ingenol-3-mebutate, 13-O-isobutyryl-12-deoxyphorbol-20-acetate, and ingenol 3,20-dibenzoate, all exhibiting weak anti-CHIKV activities, were detected in the EtOAc extracts of Euphorbia peplus, Euphorbia segetalis ssp. pinea, and Euphorbia pithyusa ssp. pithyusa. Given the potent anti-CHIKV activities of these Euphorbia extracts, the present study suggested that their antiviral activities are probably due to untargeted diterpenoids. PMID- 26151858 TI - Comparative transcriptome analysis reveals defense-related genes and pathways against downy mildew in Vitis amurensis grapevine. AB - Downy mildew (DM), caused by oomycete Plasmopara viticola (Pv), can lead to severe damage to Vitis vinifera grapevines. Vitis amurensis has generally been regarded as a DM resistant species. However, when V. amurensis 'Shuanghong' were inoculated with Pv strains 'ZJ-1-1' and 'JL-7-2', the former led to obvious DM symptoms (compatible), while the latter did not develop any DM symptoms but exhibited necrosis (incompatible). In order to underlie molecular mechanism in DM resistance, mRNA-seq based expression profiling of 'Shuanghong' was compared at 12, 24, 48 and 72 h post inoculation (hpi) with these two strains. Specific genes and their corresponding pathways responsible for incompatible interaction were extracted by comparing with compatible interaction. In the incompatible interaction, 37 resistance (R) genes were more expressed at the early stage of infection (12 hpi). Similarly, genes involved in defense signaling, including MAPK. ROS/NO, SA, JA, ET and ABA pathways, and genes associated with defense related metabolites synthesis, such as pathogenesis-related genes and phenylpropanoids/stilbenoids/flavonoids biosynthesizing genes, were also activated mainly during the early stages of infection. On the other hand, Ca(2+) signaling and primary metabolism, such as photosynthesis and fatty acid synthesis, were more repressed after 'JL-7-2' challenge. Further quantification of some key defense-related factors, including phytohormones, phytoalexins and ROS, generally showed much more accumulation during the incompatible interaction, indicating their important roles in DM defense. In addition, a total of 43 and 52 RxLR effectors were detected during 'JL-7-2' and 'ZJ-1-1' infection processes, respectively. PMID- 26151859 TI - Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation. AB - Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-beta superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletal myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on the complex crosstalk between both growth factors. PMID- 26151857 TI - Global analysis of biogenesis, stability and sub-cellular localization of lncRNAs mapping to intragenic regions of the human genome. AB - Long noncoding RNAs (lncRNAs) that map to intragenic regions of the human genome with the same (intronic lncRNAs) or opposite orientation (antisense lncRNAs) relative to protein-coding mRNAs have been largely dismissed from biochemical and functional characterization due to the belief that they are mRNA precursors, byproducts of RNA splicing or simply transcriptional noise. In this work, we used a custom microarray to investigate aspects of the biogenesis, processing, stability, evolutionary conservation, and cellular localization of ~ 6,000 intronic lncRNAs and ~ 10,000 antisense lncRNAs. Most intronic (2,903 of 3,427, 85%) and antisense lncRNAs (4,945 of 5,214, 95%) expressed in HeLa cells showed evidence of 5' cap modification, compatible with their transcription by RNAP II. Antisense lncRNAs (median t1/2 = 3.9 h) were significantly (p < 0.0001) more stable than mRNAs (median t1/2 = 3.2 h), whereas intronic lncRNAs (median t1/2 = 2.1 h) comprised a more heterogeneous class that included both stable (t1/2 > 3 h) and unstable (t1/2 < 1 h) transcripts. Intragenic lncRNAs display evidence of evolutionary conservation, have little/no coding potential and were ubiquitously detected in the cytoplasm. Notably, a fraction of the intronic and antisense lncRNAs (13 and 15%, respectively) were expressed from loci at which the corresponding host mRNA was not detected. The abundances of a subset of intronic/antisense lncRNAs were correlated (r >= |0.8|) with those of genes encoding proteins involved in cell division and DNA replication. Taken together, the findings of this study contribute novel biochemical and genomic information regarding intronic and antisense lncRNAs, supporting the notion that these classes include independently transcribed RNAs with potentials for exerting regulatory functions in the cell. PMID- 26151861 TI - Use of evidence-based substance use treatment practices in Mississippi. AB - Over the past decade, substance abuse treatment professionals have begun to implement evidence-based practices (EBPs) into the treatment of substance use disorders. There is a growing body of research on the diffusion of EBP in addiction treatment; however, less is known about individual state initiatives to implement EBPs among community providers. The current study aimed to evaluate the progress of an initiative of the Mississippi Department of Mental Health (MDMH) to increase the implementation of evidence-based substance abuse treatment practices by certified providers. In addition, the study examines potential barriers to implementing these practices. To accomplish this goal, we reported the findings of two surveys of Mississippi addiction professionals conducted in 2010 and in 2013. PMID- 26151862 TI - Effect of the Amine Concentration on Phase Evolution and Densification in Printed Films Using Cu(II) Complex Ink. AB - The nucleation and growth behavior of Cu nanoparticles during thermal heating of Cu(II) complex inks for printed Cu metallization were investigated, particularly focusing on the effects of the amine concentration on the microstructure evolution and electrical conductivity. Herein, the dual effects of hexylamine as a reducing agent dissociating the carboxyl group from the precursor and a capping agent hindering the subsequent growth of Cu nuclei were confirmed. On the basis of such dual effects of amine, the sufficient complexation of the Cu(II) precursor with a high amine concentration in the ink led to the single-route growth of Cu nanoparticles during thermal heating, which resulted in the dense film with a narrow particle size distribution exhibiting a high electrical conductivity. The electrical conductivity of the film could be further enhanced by a reducing atmosphere with formic acid. Significantly, the understanding of the ink chemistry and the nucleation and growth kinetics in the metal ion complex or metal-organic decomposition (MOD) ink can provide the design rules for the formulation of the solution-type inks to control the microstructure of printed metallization. PMID- 26151863 TI - [Authors' correction]. PMID- 26151864 TI - Patient Experience Shows Little Relationship with Hospital Quality Management Strategies. AB - OBJECTIVES: Patient-reported experience measures are increasingly being used to routinely monitor the quality of care. With the increasing attention on such measures, hospital managers seek ways to systematically improve patient experience across hospital departments, in particular where outcomes are used for public reporting or reimbursement. However, it is currently unclear whether hospitals with more mature quality management systems or stronger focus on patient involvement and patient-centered care strategies perform better on patient-reported experience. We assessed the effect of such strategies on a range of patient-reported experience measures. MATERIALS AND METHODS: We employed a cross-sectional, multi-level study design randomly recruiting hospitals from the Czech Republic, France, Germany, Poland, Portugal, Spain, and Turkey between May 2011 and January 2012. Each hospital contributed patient level data for four conditions/pathways: acute myocardial infarction, stroke, hip fracture and deliveries. The outcome variables in this study were a set of patient-reported experience measures including a generic 6-item measure of patient experience (NORPEQ), a 3-item measure of patient-perceived discharge preparation (Health Care Transition Measure) and two single item measures of perceived involvement in care and hospital recommendation. Predictor variables included three hospital management strategies: maturity of the hospital quality management system, patient involvement in quality management functions and patient-centered care strategies. We used directed acyclic graphs to detail and guide the modeling of the complex relationships between predictor variables and outcome variables, and fitted multivariable linear mixed models with random intercept by hospital, and adjusted for fixed effects at the country level, hospital level and patient level. RESULTS: Overall, 74 hospitals and 276 hospital departments contributed data on 6,536 patients to this study (acute myocardial infarction n = 1,379, hip fracture n = 1,503, deliveries n = 2,088, stroke n = 1,566). Patients admitted for hip fracture and stroke had the lowest scores across the four patient reported experience measures throughout. Patients admitted after acute myocardial infarction reported highest scores on patient experience and hospital recommendation; women after delivery reported highest scores for patient involvement and health care transition. We found no substantial associations between hospital-wide quality management strategies, patient involvement in quality management, or patient-centered care strategies with any of the patient reported experience measures. CONCLUSION: This is the largest study so far to assess the complex relationship between quality management strategies and patient experience with care. Our findings suggest absence of and wide variations in the institutionalization of strategies to engage patients in quality management, or implement strategies to improve patient-centeredness of care. Seemingly counterintuitive inverse associations could be capturing a scenario where hospitals with poorer quality management were beginning to improve their patient experience. The former suggests that patient-centered care is not yet sufficiently integrated in quality management, while the latter warrants a nuanced assessment of the motivation and impact of involving patients in the design and assessment of services. PMID- 26151865 TI - Large Eddy Simulation of Air Escape through a Hospital Isolation Room Single Hinged Doorway--Validation by Using Tracer Gases and Simulated Smoke Videos. AB - The use of hospital isolation rooms has increased considerably in recent years due to the worldwide outbreaks of various emerging infectious diseases. However, the passage of staff through isolation room doors is suspected to be a cause of containment failure, especially in case of hinged doors. It is therefore important to minimize inadvertent contaminant airflow leakage across the doorway during such movements. To this end, it is essential to investigate the behavior of such airflows, especially the overall volume of air that can potentially leak across the doorway during door-opening and human passage. Experimental measurements using full-scale mock-ups are expensive and labour intensive. A useful alternative approach is the application of Computational Fluid Dynamics (CFD) modelling using a time-resolved Large Eddy Simulation (LES) method. In this study simulated air flow patterns are qualitatively compared with experimental ones, and the simulated total volume of air that escapes is compared with the experimentally measured volume. It is shown that the LES method is able to reproduce, at room scale, the complex transient airflows generated during door opening/closing motions and the passage of a human figure through the doorway between two rooms. This was a basic test case that was performed in an isothermal environment without ventilation. However, the advantage of the CFD approach is that the addition of ventilation airflows and a temperature difference between the rooms is, in principle, a relatively simple task. A standard method to observe flow structures is dosing smoke into the flow. In this paper we introduce graphical methods to simulate smoke experiments by LES, making it very easy to compare the CFD simulation to the experiments. The results demonstrate that the transient CFD simulation is a promising tool to compare different isolation room scenarios without the need to construct full-scale experimental models. The CFD model is able to reproduce the complex airflows and estimate the volume of air escaping as a function of time. In this test, the calculated migrated air volume in the CFD model differed by 20% from the experimental tracer gas measurements. In the case containing only a hinged door operation, without passage, the difference was only 10%. PMID- 26151866 TI - Ceria Nanotube Formed by Sacrificed Precursors Template through Oswald Ripening. AB - Controllable preparation of ceria nanotube was realized by hydrothermal treatment of Ce(OH)CO3 precursors. The gradually changing morphologies and microstructures of cerium oxide were characterized by X-ray powder diffraction, scanning electron microscopy and transmission electron microscopy. A top-down path is illuminated to have an insight to the morphological transformation from nanorod to nanotube by adjusting the reaction time. The growth process is investigated by preparing a series of intermediate morphologies during the shape evolution of CeO2 nanostructure based on the scanning electron microscopy image observation. On the basis of the time-dependent experimental observation, the possible formation mechanism related to oriented attachment and Oswald ripening was proposed, which might afford some guidance for the synthesis of other inorganic nanotubes. PMID- 26151868 TI - The role of multifunctional drug therapy against carbamate induced neuronal toxicity during acute and chronic phase in rats. AB - The current study has been designed to examine the effect of multifunctional drug therapy on carbofuran induced acute (2.187 mg/kg, s.c.) and sub-acute (0.2187 mg/kg, s.c.) neurotoxicity in male wistar rats. Drug treatment which includes nimodipine (Ca(2+) channel blocker), diazepam, ropinirole (dopamine agonist) and GSPE (antioxidant) was started 2h after carbofuran administration. Morris water maze was employed for aiming spatial memory. Narrow beam walk and rotarod were employed for testing motor functions. Brain acetylcholinesterase activity, thiobarbituric acid reactive species, nitrite, reduced glutathione, catalase levels, and mitochondrial complexes were also estimated. Carbofuran treatment resulted in significant development of cognitive and motor functions manifested as impairment in learning and memory along with increased thiobarbituric acid reactive species, nitrite levels and decreased acetylcholinesterase activity, reduced glutathione, catalase levels, and mitochondrial complexes. The standard antidote therapy (atropine) was not able to provide neuroprotection but was able to provide symptomatic relief. The multifunctional drug therapy attenuated carbofuran induced cognitive and motor dysfunction, acetylcholinesterase activity and other biochemical parameters. The triple combination in sub-acute study may be avoided in future as two drug combinations provide adequate neuroprotection. Thus it can be concluded that standard antidotal therapy may not provide neuroprotection while the multifunctional drug therapy offers neuroprotection against carbofuran and may dramatically increase survival and life quality. PMID- 26151867 TI - Characterization of Changes in Global Genes Expression in the Distal Colon of Loperamide-Induced Constipation SD Rats in Response to the Laxative Effects of Liriope platyphylla. AB - To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats. PMID- 26151869 TI - Optimizing conditions for production of high levels of soluble recombinant human growth hormone using Taguchi method. AB - Human growth hormone (hGH) is synthesized and stored by somatotroph cells of the anterior pituitary gland and can effect on body metabolism. This protein can be used to treat hGH deficiency, Prader-Willi syndrome and Turner syndrome. The limitations in current technology for soluble recombinant protein production, such as inclusion body formation, decrease its usage for therapeutic purposes. To achieve high levels of soluble form of recombinant human growth hormone (rhGH) we used suitable host strain, appropriate induction temperature, induction time and culture media composition. For this purpose, 32 experiments were designed using Taguchi method and the levels of produced proteins in all 32 experiments were evaluated primarily by ELISA and dot blotting and finally the purified rhGH protein products assessed by SDS-PAGE and Western blotting techniques. Our results indicate that media, bacterial strains, temperature and induction time have significant effects on the production of rhGH. The low cultivation temperature of 25 degrees C, TB media (with 3% ethanol and 0.6M glycerol), Origami strain and a 10-h induction time increased the solubility of human growth hormone. PMID- 26151870 TI - The Influence of Media Violence on Youth. AB - Research on violent television and films, video games, and music reveals unequivocal evidence that media violence increases the likelihood of aggressive and violent behavior in both immediate and long-term contexts. The effects appear larger for milder than for more severe forms of aggression, but the effects on severe forms of violence are also substantial (r = .13 to .32) when compared with effects of other violence risk factors or medical effects deemed important by the medical community (e.g., effect of aspirin on heart attacks). The research base is large; diverse in methods, samples, and media genres; and consistent in overall findings. The evidence is clearest within the most extensively researched domain, television and film violence. The growing body of video-game research yields essentially the same conclusions. Short-term exposure increases the likelihood of physically and verbally aggressive behavior, aggressive thoughts, and aggressive emotions. Recent large-scale longitudinal studies provide converging evidence linking frequent exposure to violent media in childhood with aggression later in life, including physical assaults and spouse abuse. Because extremely violent criminal behaviors (e.g., forcible rape, aggravated assault, homicide) are rare, new longitudinal studies with larger samples are needed to estimate accurately how much habitual childhood exposure to media violence increases the risk for extreme violence. Well-supported theory delineates why and when exposure to media violence increases aggression and violence. Media violence produces short-term increases by priming existing aggressive scripts and cognitions, increasing physiological arousal, and triggering an automatic tendency to imitate observed behaviors. Media violence produces long-term effects via several types of learning processes leading to the acquisition of lasting (and automatically accessible) aggressive scripts, interpretational schemas, and aggression-supporting beliefs about social behavior, and by reducing individuals' normal negative emotional responses to violence (i.e., desensitization). Certain characteristics of viewers (e.g., identification with aggressive characters), social environments (e.g., parental influences), and media content (e.g., attractiveness of the perpetrator) can influence the degree to which media violence affects aggression, but there are some inconsistencies in research results. This research also suggests some avenues for preventive intervention (e.g., parental supervision, interpretation, and control of children's media use). However, extant research on moderators suggests that no one is wholly immune to the effects of media violence. Recent surveys reveal an extensive presence of violence in modern media. Furthermore, many children and youth spend an inordinate amount of time consuming violent media. Although it is clear that reducing exposure to media violence will reduce aggression and violence, it is less clear what sorts of interventions will produce a reduction in exposure. The sparse research literature suggests that counterattitudinal and parental mediation interventions are likely to yield beneficial effects, but that media literacy interventions by themselves are unsuccessful. Though the scientific debate over whether media violence increases aggression and violence is essentially over, several critical tasks remain. Additional laboratory and field studies are needed for a better understanding of underlying psychological processes, which eventually should lead to more effective interventions. Large scale longitudinal studies would help specify the magnitude of media-violence effects on the most severe types of violence. Meeting the larger societal challenge of providing children and youth with a much healthier media diet may prove to be more difficult and costly, especially if the scientific, news, public policy, and entertainment communities fail to educate the general public about the real risks of media-violence exposure to children and youth. PMID- 26151871 TI - Science, Politics, and Violence in the Media. PMID- 26151872 TI - Authors' Note. PMID- 26151873 TI - Efficient Construction of Azaspiro[4.5]trienone Libraries via Tandem Ugi 4CC/Electrophilic ipso-Iodocyclization in One-Pot. AB - A solution-phase parallel synthesis of pharmaceutically important azaspiro[4.5]trienones has been developed by performing tandem Ugi four-component condensation (U4CC), involving substituted p-anisidines, aldehydes, 3-alkyl/aryl propiolic acids, and isocyanides, and iodine-mediated ipso-iodocyclization in one pot. This highly atom economical process produced functionalized azaspiro[4.5]trienones in good to excellent overall yields and products were easily isolated by precipitation followed by crystallization. These vinyl-iodide bearing azaspiro[4.5]trienones were utilized for further modifications through Suzuki coupling and deiodination reaction to demonstrate the suitability of these products for various palladium catalyzed modifications. The present method provides an easy access to highly functionalized azaspiro[4.5]trienones that can be useful in drug discovery research. PMID- 26151874 TI - Investigations on the Flat-Detector Computed Tomography-Based CBV Map Acquisition Using a Left Ventricle Contrast Media Injection Protocol. AB - OBJECTIVES: Cerebral blood volume (CBV) acquired with the use of flat-detector computed tomography with contrast media (CM) injected at the ascending aorta provides real-time brain functional information with minimized CM usage; however, unexpected asymmetric perfusion is observed for certain patients without cerebral circulatory disorders. This work tested the feasibility of left ventricle (LV) CM injection to achieve symmetric perfusion. METHODS: CBV maps were acquired for 10 patients without perfusion-related cerebral abnormities. Perfusion symmetry was predicted with the use of color-coded quantitative digital subtracted angiography with CM injected at ascending aorta. Time density curves were extracted at bilateral common carotid arteries with area under curves calculated. Planes were selected on CBV maps with regions of interest defined covering characteristic regions, where asymmetric perfusion most likely to appear. RESULTS: No adverse physiological changes were detected for any patient. Non-uniform CM distributions were detected for 4 patients with relative area under curves 0.66 +/- 0.03, indicating asymmetric perfusion using ascending aorta injection. With LV injection, all the patients demonstrated good perfusion symmetry with relative CBV 1.03 +/- 0.07. CONCLUSION: CBV maps acquisition with LV injection offered an approach to acquire immediate brain functional information for patients who are limited by asymmetric perfusion using ascending aorta injection and are sensitive to CM dose. PMID- 26151875 TI - Ralph Bingham Cloward (1908-2000): Spine Polymath. AB - Dr. Ralph Bingham Cloward, an American neurosurgeon, revolutionized the field of modern spine surgery with his lifelong innovative and pioneering contribution. He described the posterior lumbar interbody fusion and anterior cervical discectomy and fusion. He engineered more than 100 instruments, which shared his intellect and wisdom to the neurosurgery and orthopedic fraternity across the globe. He was also the first person to set up a bone bank in the United States. He rightfully deserves the title "Michelangelo of neurosurgery" for his exceptional work. PMID- 26151876 TI - POSIT: Flexible Shape-Guided Docking For Pose Prediction. AB - We present a new approach to structure-based drug design (POSIT) rigorously built on the simple concept that pose prediction is intimately coupled to the quality and availability of experimental structural data. We demonstrate the feasibility of the approach by performing retrospective analyses on three data sets designed to explore the strengths and weaknesses of POSIT relative to existing methods. We then present results documenting 2.5 years of prospective use of POSIT across a variety of structure-based industrial drug-discovery research projects. We find that POSIT is well-suited to guiding research decision making for structure-based design and, in particular, excels at enabling lead-optimization campaigns. We show that the POSIT framework can drive superior pose-prediction performance and generate results that naturally lend themselves to prospective decision making during lead optimization. We believe the results presented here are (1) the largest prospective validation of a pose prediction method reported to date (71 crystal structures); (2) provide an unprecedented look at the scope of impact of a computational tool; and (3) represent a first-of-its-kind analysis. We hope that this work inspires additional studies that look at the real impact and performance of computational research tools on prospective drug design. PMID- 26151878 TI - Lake Sediments Tell the Story of Climate Change. PMID- 26151880 TI - Functionalization of micromodels with kaolinite for investigation of low salinity oil-recovery processes. AB - Sandstone formations are ubiquitous in both aquifers and petroleum reservoirs, of which clay is a major constituent. The release of clay particles from pore surfaces as a result of reduced injection fluid salinity can greatly modify the recovery of hydrocarbons from subsurface formations by shifting the wettability properties of the rock. In this paper we demonstrate a microfluidic approach whereby kaolinite is deposited into a two-dimensional microfluidic network (micromodel) to enable direct pore-scale, real-time visualization of fluid-solid interactions with representative pore-geometry and realistic surface interactions between the reservoir fluids and the formation rock. Structural characterization of deposited kaolinite particles agrees well with natural modes of occurrence in Berea sandstones; hence, the clay deposition method developed in this work is validated. Specifically, more than 90% of the deposited clay particles formed pore-lining structures and the remainder formed pore bridging structures. Further, regions of highly concentrated clay deposition likely leading to so called Dalmatian wetting properties were found throughout the micromodel. Two post-deposition treatments are described whereby clay is adhered to the silicon surface reversibly and irreversibly resulting in microfluidic systems that are amenable to studies on (i) the fundamental mechanisms governing the increased oil recovery during low salinity waterfloods and (ii) the effect of a mixed-wet surface on oil recovery, respectively. The reversibly functionalized platform is used to determine the conditions at which stably adhered clay particles detach. Specifically, injection brine salinity below 6000 ppm of NaCl induced kaolinite particle release from the silicon surface. Furthermore, when applied to an aged system with crude oil, the low salinity waterflood recovered an additional 14% of the original oil in place compared to waterflooding with the formation brine. PMID- 26151882 TI - The Effect of a Shock Absorber on Spatiotemporal Parameters and Ground Reaction Forces of Forearm Crutch Ambulation. AB - Forearm crutches are a commonly used assistive device to aid the ambulation of people with lower limb impairment. Due to the structure of the joints of the upper limb, the loading patterns during crutch-walking can be detrimental to the user. Shock-absorbed or compliant crutches may reduce ground contact impact, potentially benefitting the user. In this study, the authors performed a biomechanical evaluation of a shock absorber crutch, which uses an elastomeric system to absorb impact. Ground reaction forces (GRFs) and spatiotemporal parameters were compared between shock absorbed and standard crutches. Results indicate no significant differences to spatiotemporal parameters and peak ground reaction forces between the crutches. There is an initial impact spike during crutch strike when using shock absorbed crutches, after which the rate of force development is moderately decreased when compared with a standard crutch. The practical benefit of a small reduction in force is questionable and more work must be undertaken to further optimise shock absorber design. PMID- 26151881 TI - Engineering near-infrared single-photon emitters with optically active spins in ultrapure silicon carbide. AB - Vacancy-related centres in silicon carbide are attracting growing attention because of their appealing optical and spin properties. These atomic-scale defects can be created using electron or neutron irradiation; however, their precise engineering has not been demonstrated yet. Here, silicon vacancies are generated in a nuclear reactor and their density is controlled over eight orders of magnitude within an accuracy down to a single vacancy level. An isolated silicon vacancy serves as a near-infrared photostable single-photon emitter, operating even at room temperature. The vacancy spins can be manipulated using an optically detected magnetic resonance technique, and we determine the transition rates and absorption cross-section, describing the intensity-dependent photophysics of these emitters. The on-demand engineering of optically active spins in technologically friendly materials is a crucial step toward implementation of both maser amplifiers, requiring high-density spin ensembles, and qubits based on single spins. PMID- 26151883 TI - Deglucose chikusetsusaponin IVa isolated from Rhizoma Panacis Majoris induces apoptosis in human HepG2 hepatoma cells. AB - Deglucose chikusetsusaponin IVa (DCIVa), isolated from Rhizoma Panacis Majoris, a widely used traditional Chinese medicine, is a type of oleanane triterpenoids. Various previous studies have demonstrated that oleanane triterpenoids exhibit cytotoxic activity against various types of cancer cells. However, whether DCIVa exerts an antitumor effect remains to be elucidated. The present study aimed to assess the effect of DCIVa on cancer cells using the HepG2 hepatocellular carcinoma cell line and determine the underlying mechanism. Using an MTT assay, it was demonstrated that DCIVa inhibited cell growth and viability in a dose- and time-dependent manner. Typical apoptotic features, including chromatin condensation and margination at the nuclear periphery, and apoptotic body formation were induced by DCIVa and were detected by transmission electron microscopy. In addition, nuclear condensation and fragmentation were also observed by Hoechst 33258 staining. Furthermore, flow cytometric analysis revealed that DCIVa increased cell apoptosis and G2/M cell cycle arrest dose dependently. Western blot analysis further demonstrated that DCIVa upregulated the expression of the pro-apoptotic protein, Bax, and downregulated the expression of the anti-apoptotic protein, Bcl-2. In conclusion, the present study demonstrated for the first time, to the best of our knowledge, that DCIVa exerts potent cytotoxic effects on HepG2 cells through induction of cell apoptosis and cell cycle arrest, and may be utilized as a potential anticancer agent. PMID- 26151884 TI - A hybrid density functional theory study of the anion distribution and applied electronic properties of the LaTiO2N semiconductor photocatalyst. AB - Although the crystallographic space group has been determined, detailed first principles calculations of the LaTiO2N semiconductor photocatalyst crystal have not been performed because of the nitrogen/oxygen sosoloid-like anion distribution. In this study, based on the Heyd-Scuseria-Ernzerhof method and experimental anion content, we present the possibility of determining detailed information about the LaTiO2N sosoloid-like anion distribution by dividing the anions into possible primitive cells. The detailed information about the anion distribution based on the characteristics of the energetically acceptable primitive cell structures suggests that the LaTiO2N structure is composed of aperiodic stacks of six building-block primitive cells, the non-vacancy primitive cells are located at the surface as effective photoreaction sites, and vacancy structures are located in the bulk. The surface oxide-rich structures increase the near-surface conduction band minimum rise and strengthen photoelectron transport to the bulk, while the content of the bulk vacancy structures should be balanced because of being out of photoreactions. This study is expected to provide a different perspective to understanding the LaTiO2N sosoloid-like anion distribution. PMID- 26151886 TI - Assessing the influence of diurnal variations and selective Xa inhibition on whole blood aggregometry. AB - A biological rhythm in platelet function is well known. Multiple electrode aggregometry (MEA) is a widely used assay to measure platelet aggregability. Rivaroxaban is a new oral anticoagulant frequently used in an increasing number of indications. In this randomized, crossover trial we investigated whether a biological rhythm exists in MEA measurements and potential effects of rivaroxaban on platelet aggregation. Sixteen healthy volunteers were included in the study and blood samples were obtained at 08:00, 12:00, 16:00 and 20:00 h. Each subject was tested without rivaroxaban intake first and randomly assigned to 3 days of rivaroxaban intake at 08:00 or 3 days of rivaroxaban intake at 20:00 h and vice versa. In MEA measurements, a significant increase in platelet aggregation after addition of ristocetin at 12:00 h compared to other investigated time-points (122 +/- 8 AU at 12:00 h vs. 109 +/- 9 AU at 08:00 h, 114 +/- 10 AU at 16:00 h and 103 +/- 8 AU at 20:00 h, p = 0.027) could be detected. There was no biological rhythm detectable using other agonists (ADP, arachidonic acid, thrombin-receptor activating peptide-6). After rivaroxaban intake at 08:00 h an increased ristocetin-induced platelet aggregation was measured in the next morning (126 +/- 4 AU (rivaroxaban at 08:00 h) vs. 109 +/- 9 AU (no rivaroxaban), 111 +/- 6 AU (rivaroxaban at 20:00 h; p = 0.002). No other effects of rivaroxaban on platelet function were found. We detected a biological rhythm in ristocetin-induced platelet aggregation with a peak at 12:00 h (noon). No influence of selective Xa inhibition on platelet aggregation was detected. PMID- 26151887 TI - Reference intervals of plasma matrix metalloproteinases 2, 3, and 9 and serum asymmetric dimethylarginine levels. AB - OBJECTIVE: The present study aimed to verify the reference intervals of plasma matrix metalloproteinases (MMPs) 2, 3, and 9 and serum asymmetric dimethylarginine (ADMA) in a healthy population with an average age corresponding to that of patients with cardiovascular diseases. METHODS: The study included 180 healthy volunteers. Plasma MMP-2, MMP-3, MMP-9, and serum ADMA levels were determined using an enzyme-linked immunosorbent assay. These levels were analyzed for association with age and gender. The Cbstat5, R software, and NCSS 2007 programs were used for statistical analysis. RESULTS: The average volunteer age was 47.4 years in the group in which MMP-3 and ADMA were analyzed, 40.3 years in the MMP-9 group, and 47.8 years for the MMP-2 group. Serum ADMA levels were determined to be independent of age and gender. Plasma MMP-2 levels were significantly correlated with age (p = 0.001), with lower levels detected in persons <= 49 years of age. Plasma MMP-3 was significantly associated with both age (p < 0.0001) and gender, with lower levels detected in persons of <= 47 years of age and among women. Plasma MMP-9 levels were not age dependent, but were associated with gender (p = 0.014), showing lower levels in women. CONCLUSIONS: Reference intervals of heparin-plasma MMP-2, MMP-3, and MMP-9 and serum ADMA levels were determined. MMP-2 and MMP-3 levels were found to be age dependent, and MMP-3 and MMP-9 levels were gender dependent. PMID- 26151889 TI - Two-dimensional magnetotransport in a black phosphorus naked quantum well. AB - Black phosphorus (bP) is the second known elemental allotrope with a layered crystal structure that can be mechanically exfoliated to atomic layer thickness. Unlike metallic graphite and semi-metallic graphene, bP is a semiconductor in both bulk and few-layer form. Here we fabricate bP-naked quantum wells in a back gated field effect transistor geometry with bP thicknesses ranging from 6+/-1 nm to 47+/-1 nm. Using a polymer encapsulant, we suppress bP oxidation and observe field effect mobilities up to 900 cm(2) V(-1) s(-1) and on/off current ratios exceeding 10(5). Shubnikov-de Haas oscillations observed in magnetic fields up to 35 T reveal a 2D hole gas with Schrodinger fermion character in a surface accumulation layer. Our work demonstrates that 2D electronic structure and 2D atomic structure are independent. 2D carrier confinement can be achieved without approaching atomic layer thickness, advantageous for materials that become increasingly reactive in the few-layer limit such as bP. PMID- 26151890 TI - Erratum: Global reemergence of enterovirus D68 as an important pathogen for acute respiratory infections. PMID- 26151888 TI - Silicone Implants with Smooth Surfaces Induce Thinner but Denser Fibrotic Capsules Compared to Those with Textured Surfaces in a Rodent Model. AB - PURPOSE: Capsular contracture is the most frequent long-term complication after implant-based breast reconstruction or augmentation. The aim of this study was to evaluate the impact of implant surface properties on fibrotic capsule formation in an animal model. MATERIALS AND METHODS: Twenty-four rats received 1 scaled down silicone implant each; 12 of the rats received implants with textured surfaces, and the other 12 received implants with smooth surfaces. After 60 and 120 days, rats in each group underwent 7-Tesla Magnetic Resonance Imaging (MRI) and high-resolution ultrasound (HR-US), and specimens of the capsules were acquired and used to measure capsule thickness through histology, collagen density through picro sirius red staining, and analyses of expression of pro fibrotic and inflammatory genes (Collagen1-4, TGFb1, TGFb3, Smad3, IL4, IL10, IL13, CD68) through qRT-PCR. Furthermore, MRI data were processed to obtain capsule volume and implant surface area. RESULTS: On day 60, histology and HR-US showed that fibrotic capsules were significantly thicker in the textured implant group with respect to the smooth implant group (p<0.05). However, this difference did not persist on day 120 (p=0.56). Capsule thickness decreased significantly over the study period in both smooth and textured implant groups (p<0.05). Thickness measurements were substantiated by MRI analysis and volumes changed accordingly. Implant surface area did not vary between study dates, but it was different between implant types. On day 60, the density of collagen in the fibrotic capsules was significantly lower in the textured implant group with respect to the smooth group (p<0.05), but again this difference did not persist on day 120 (p=0.67). Collagen 1 and CD68 were respectively over- and under expressed in the textured implant group on day 60. Significant differences in the expression of other genes were not observed. CONCLUSION: Silicone implants with textured surfaces led to temporarily thicker but less dense fibrotic capsules compared with smooth surfaces. 7-Tesla MRI and HR-US are capable for non-invasive in-vivo assessment of capsular fibrosis in an animal model and can provide unique insights into the fibrotic process by 3D reconstruction and surface area measurement. PMID- 26151885 TI - Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs. AB - The targeted endocytosis and redistribution of transmembrane receptors among membrane-bound subcellular organelles are vital for their correct signaling and physiological functions. Membrane receptors committed for internalization and trafficking pathways are sorted into coated vesicles. Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and elicit the generation of intracellular second messenger cyclic guanosine 3',5'-monophosphate (cGMP), which lowers blood pressure and incidence of heart failure. After ligand binding, the receptor is rapidly internalized, sequestrated, and redistributed into intracellular locations. Thus, NPRA is considered a dynamic cellular macromolecule that traverses different subcellular locations through its lifetime. The utilization of pharmacologic and molecular perturbants has helped in delineating the pathways of endocytosis, trafficking, down-regulation, and degradation of membrane receptors in intact cells. This review describes the investigation of the mechanisms of internalization, trafficking, and redistribution of NPRA compared with other cell surface receptors from the plasma membrane into the cell interior. The roles of different short-signal peptide sequence motifs in the internalization and trafficking of other membrane receptors have been briefly reviewed and their potential significance in the internalization and trafficking of NPRA is discussed. PMID- 26151891 TI - Microscopic Retroperitoneal Varicocelectomy With Artery and Lymphatic Sparing: An Alternative Treatment for Varicocele in Infertile Men. AB - OBJECTIVE: To compare the therapeutic effect of arterial and lymphatic sparing microscopic retroperitoneal varicocelectomy (MRV) with that of microscopic subinguinal varicocelectomy (MSV) for treatment of varicocele in infertile men. METHODS: We conducted a prospective and controlled study to evaluate the therapeutic efficacy of MRV and MSV for treatment of varicocele in infertile men. A total of 80 patients were randomly chosen to undergo MRV (n = 40) or MSV (n = 40) treatment. All patients were followed up at 3, 6, and 12 months after surgery. Semen parameters, pregnancy, recurrence, and complications were examined. RESULTS: Mean operation time in the MRV group was significantly shorter than that in MSV group (38.92 +/- 5.67 min vs 91.35 +/- 15.08 min), and the number of observed spermatic veins in MRV group was significantly less than that in MSV group (3.59 +/- 0.76 vs 18.22 +/- 2.83). Sperm count and motility were significantly improved at 12 months follow-up in both groups compared with preoperative values, and the sperm count in the MRV group at 3 months was significantly higher than that in MSV group. Moreover, the incidence of scrotal edema was higher in the MSV group, although natural pregnancy rate was not significantly different between 2 groups at 1-year follow-up (42.1% vs 44.7%). CONCLUSION: MRV with artery and lymphatic sparing is a simple and effective technique for treatment of varicocele in infertile men. PMID- 26151892 TI - Healing of Donor-site Buccal Mucosa Urethroplasty. AB - Buccal mucosal graft represents the gold standard graft material for urethroplasty because of its thick epithelium and a thin lamina propria for maximal graft uptake. There is an ongoing debate whether to close the buccal graft donor site. We show a unique look at buccal donor site healing through serial pictures over a 100-day period. In this patient, the anterior half of the buccal donor site was closed at the time of harvest, allowing real-time observation of wound healing from both the closed and open aspects of the wound. PMID- 26151893 TI - Cloning and identification of a YY-1 homolog as a potential transcription factor from Pinctada fucata. AB - Biomineralization is an important and ubiquitous process in organisms. The shell formation of mollusks is a typical biomineral physical activity and is used as a canonical model in biomineralization research. Most recent studies focused on the identification of matrix proteins involved in shell formation; however, little is known about their transcriptional regulation mechanism, especially the transcription factors involved in shell formation. In this study, we identified a homolog of the YY-1 transcriptional factor from Pinctada fucata, named Pf-YY-1, and characterized its expression pattern and biological functions. Pf-YY-1 has a typical zinc finger motif highly similar to those in humans, mice, and other higher organisms, which indicated its DNA-binding capability and its function as a transcription factor. Pf-YY-1 is ubiquitously expressed in many tissues, but at a higher level in the mantle, which suggested a role in biomineralization. The expression pattern of Pf-YY-1 during pearl sac development was quite similar to, and was synchronized with, those of Prisilkin-39, ACCBP, and other genes involved in biomineralization, which also suggested its function in biomineralization. PMID- 26151894 TI - Characterization of the fundamental properties of the N-terminal truncation (Delta exon 1) variant of estrogen receptor alpha in the rat. AB - The estrogen receptor alpha (ERalpha) directs transactivation of target genes, and splice variants have been shown to exhibit altered activation properties. We previously documented the complicated alternative promoter usage and splicing patterns of the rat ERalpha gene; however, the information was restricted to a few specific organs. Therefore, we re-examined the rat mRNA profiles of ERalpha, including the generation of the exon 1-skipping, ERalpha46 transcript in a wider variety of rat organs and further characterized the fundamental functional properties of rat ERalpha46 variants. With the use of RT-PCR, we discovered unique distribution and splicing patterns for promoter-specific ERalpha isoforms, as well as the extensive expression of the Delta exon 1 variant in the rat. Similar to wild-type ERalpha, an immunocytochemical analysis showed a predominant localization of ERalpha46 proteins in the nuclei of transfected cells. Luciferase reporter assays revealed that ERalpha46 variants stimulated the transcriptional activity of an estrogen response element-driven promoter in response to estrogen. In addition, the variants exhibited distinct transactivation and reactivity to 4 hydroxytamoxifen in different cell types. Although the alternative splicing patterns are species-specific, the profiles of the alternative use of promoters, and the fundamental properties of the rat ERalpha46 variant are similar to those of human and mouse homologs. Therefore, the present study provides fundamental and useful information for further research into the regulation and functions of ERalpha gene variants. PMID- 26151895 TI - Analysis of the complete mitochondrial genome and characterization of diverse NUMTs of Macaca leonina. AB - As a non-human primate, the pig-tailed macaque has received wide attention because it can be infected by HIV-1. In this study, we determined the complete mtDNA sequence of the northern pig-tailed macaque (Macaca leonina). Unexpectedly, during the amplification of the mtDNA control region (D-loop region) we observed several D-loop-like sequences, which were NUMTs (nuclear mitochondrial sequences) and a total of 14 D-loop-like NUMT haplotypes were later identified in five individuals. The neighbor-joining tree and estimated divergence time based on these D-loop-like NUMT sequences of M. leonina provide some insights into the understanding of the evolutionary history of NUMTs. D-loop-like haplotypes G and H, which also exist in the nuclear genome of mulatta, appear to have been translocated into the nuclear genome before the divergence of M. mulatta and M. leonina. The other D-loop-like NUMT haplotypes were translocated into the nuclear genome of M. leonina after the divergence of the two species. Later sequence conversion was predicted to occur among these 14 D-loop-like NUMT haplotypes. The overall structure of the mtDNA of M. leonina was found to be similar to that seen in other mammalian mitochondrial genomes. Phylogenetic analysis based on the maximum likelihood method shows M. leonina clustered with Macaca silenus among the analyzed mammalian species. PMID- 26151897 TI - Investigating changes in the redox state of Photosystem I at low pH. AB - Changes in the redox state of Photosystem I (PSI) were studied in spinach leaf discs suspended in buffers of different pH (pH 7.5, 6.5, 5.5 and 4.5). By measuring absorbance changes at 820 nm, it was observed that under normal conditions, the electrons were supplied by Photosystem II (PSII) for the photo oxidation of P700 while in the presence of DCMU when electrons coming from PSII are blocked, cyclic electron flow (CEF) around PSI was the major source for the absorbance changes observed at 820 nm. This was supported by complete inhibition in the reduction of both single turnover (ST) area and multiple turnover (MT) area, in the presence of DCMU, which is generally filled up by the electrons coming from PSII. In the absence of DCMU, the intersystem electron pool or plastoquinone (PQ) pool was increased at low pH which was probably due to enhanced cyclic electron flow around PSI. Our results also suggest that at low pH, in the absence of DCMU, the major contribution for faster dark re-reduction of P700(+) is attributed mainly by PSII and CEF PSI while in the presence of DCMU, the significant contribution is provided by CEF PSI and other stromal components. PMID- 26151896 TI - Duplications in RB1CC1 are associated with schizophrenia; identification in large European sample sets. AB - Schizophrenia (SCZ) is a severe and debilitating neuropsychiatric disorder with an estimated heritability of ~80%. Recently, de novo mutations, identified by next-generation sequencing (NGS) technology, have been suggested to contribute to the risk of developing SCZ. Although these studies show an overall excess of de novo mutations among patients compared with controls, it is not easy to pinpoint specific genes hit by de novo mutations as actually involved in the disease process. Importantly, support for a specific gene can be provided by the identification of additional alterations in several independent patients. We took advantage of existing genome-wide single-nucleotide polymorphism data sets to screen for deletions or duplications (copy number variations, CNVs) in genes previously implicated by NGS studies. Our approach was based on the observation that CNVs constitute part of the mutational spectrum in many human disease associated genes. In a discovery step, we investigated whether CNVs in 55 candidate genes, suggested from NGS studies, were more frequent among 1637 patients compared with 1627 controls. Duplications in RB1CC1 were overrepresented among patients. This finding was followed-up in large, independent European sample sets. In the combined analysis, totaling 8461 patients and 112 871 controls, duplications in RB1CC1 were found to be associated with SCZ (P=1.29 * 10(-5); odds ratio=8.58). Our study provides evidence for rare duplications in RB1CC1 as a risk factor for SCZ. PMID- 26151899 TI - Correction: Glycosylation enhances the aqueous sensitivity and lowers the cytotoxicity of a naphthalimide zinc ion fluorescence probe. AB - Correction for 'Glycosylation enhances the aqueous sensitivity and lowers the cytotoxicity of a naphthalimide zinc ion fluorescence probe' by Lei Dong et al., Chem. Commun., 2015, DOI: 10.1039/c5cc04357c. PMID- 26151898 TI - Inhibition of SENP3 by lentivirus induces suppression of apoptosis in experimental subarachnoid hemorrhage in rats. AB - BACKGROUND: Subarachnoid hemorrhage (SAH) is one of the life-threatening diseases with high morbidity and mortality rates. SUMO-specific proteases 3 (SENP3), a member of the small ubiquitin-like modifier specific protease family, was identified as an isopeptidase that deconjugates SUMOylation (The covalent modification by SUMO) of modified protein substrates. It is reported that SUMO 2/3 conjugation, a member of SUMOylation, presented neuroprotection. The study aimed to evaluate the expression of SENP3 and to explore its potential role in SAH. MATERIALS AND METHODS: A total of 108 Sprague Dawley (SD) rats were randomly divided into 2 parts experiment and 9 subgroups (part 1:Sham group, SAH group, SAH+NAC group, SAH+vehicle group; part 2: Sham group, SAH group, SAH+lv-SENP3 group, SAH+lv-null group, SAH+NS group). 7 days before SAH, lentivirus was administrated into rats' left lateral ventricle to down-regulate SENP3. Experimental SAH was imitated by injection with 0.3ml nonheparinized autoblood into the prechiasmatic cistern. MDA levels, SOD activities, and GSH contents were detected to evaluate oxidative stress level. SENP3 and cleaved caspase 3 were detected by western blot, apoptosis was observed by TUNEL staining. RESULTS: High oxidative stress level following SAH induced rising of SENP3. And inhibition of SENP3 by lentivirus induces suppression of apoptosis in experimental subarachnoid hemorrhage in rats. CONCLUSION: When SENP3 accumulated by high oxidative stress, caspase 3 activated subsequently. And it leads to more severe apoptosis than physiological. PMID- 26151900 TI - Stability of Word-Retrieval Errors With the AphasiaBank Stimuli. AB - PURPOSE: This study examined the test-retest reliability of select measures of word-retrieval errors in narrative discourses of individuals with aphasia assessed with the AphasiaBank stimuli. METHOD: Ten participants with aphasia were video recorded during 2 sessions producing narratives elicited with pictures. Discourses were transcribed and coded using AphasiaBank procedures, then analyzed for the stability of rates of phonological errors, semantic errors, false starts, time fillers, and repetitions per minute. Values for correlation coefficients and the minimal detectable change score were used to assess stability for research and clinical decision making. RESULTS: There was poor test-retest reliability when the discourses were analyzed by each narrative subgenre. When the narrative discourses were combined for analysis, several measures appeared to be sufficiently stable across sessions for use in group studies, and 1 could be adequately stable for making clinical decisions about an individual. CONCLUSIONS: Because the short speech samples yielded by the subgenre narrative analyses demonstrated poor test-retest reliability, it is recommended that all of the picture-based narrative discourse tasks be combined for analysis of word retrieval impairments when the AphasiaBank stimuli are used. However, the confidence intervals associated with the reliability coefficients obtained in this study suggest caution in using the measures if they are based on performance in a single session. More investigations of the test-retest reliability of measures used to study language impairment in discourse contexts are essential. PMID- 26151901 TI - NEGotiating Cell Identity through Regulated Cytoplasmic Polyadenylation. AB - In this issue of Developmental Cell, Elewa et al. (2015) show that combinatorial action of RNA binding proteins modulates poly(A) tail length of maternal mRNAs, leading to asymmetric expression of a cell fate determinant in early C. elegans embryos. Genome-wide profiling suggests this mechanism may be widely used to establish cell identities. PMID- 26151902 TI - Stromules: Signal Conduits for Plant Immunity. AB - The chloroplast is a primary site for the production of immune signals in plants. In this issue of Developmental Cell, Caplan et al. (2015) report that chloroplasts send out stromules as signal conduits for transmission of these immune signals to the nucleus during effector-triggered immunity. PMID- 26151903 TI - Mechanisms of Vessel Pruning and Regression. AB - The field of angiogenesis research has primarily focused on the mechanisms of sprouting angiogenesis. Yet vascular networks formed by vessel sprouting subsequently undergo extensive vascular remodeling to form a functional and mature vasculature. This "trimming" includes distinct processes of vascular pruning, the regression of selected vascular branches. In some situations complete vascular networks may undergo physiological regression. Vessel regression is an understudied yet emerging field of research. This review summarizes the state-of-the-art of vessel pruning and regression with a focus on the cellular processes and the molecular regulators of vessel maintenance and regression. PMID- 26151905 TI - Orientation, Evaluation, and Integration of Part-Time Nursing Faculty. AB - This study helps to quantify and describe orientation, evaluation, and integration practices pertaining to part-time clinical nursing faculty teaching in prelicensure nursing education programs. A researcher designed Web-based survey was used to collect information from a convenience sample of part-time clinical nursing faculty teaching in prelicensure nursing programs. Survey questions focused on the amount and type of orientation, evaluation, and integration practices. Descriptive statistics were used to analyze results. Respondents reported on average four hours of orientation, with close to half reporting no more than two hours. Evaluative feedback was received much more often from students than from full-time faculty. Most respondents reported receiving some degree of mentoring and that it was easy to get help from full time faculty. Respondents reported being most informed about student evaluation procedures, grading, and the steps to take when students are not meeting course objectives, and less informed about changes to ongoing curriculum and policy. PMID- 26151904 TI - Establishment of Centromeric Chromatin by the CENP-A Assembly Factor CAL1 Requires FACT-Mediated Transcription. AB - Centromeres are essential chromosomal structures that mediate accurate chromosome segregation during cell division. Centromeres are specified epigenetically by the heritable incorporation of the centromeric histone H3 variant CENP-A. While many of the primary factors that mediate centromeric deposition of CENP-A are known, the chromatin and DNA requirements of this process have remained elusive. Here, we uncover a role for transcription in Drosophila CENP-A deposition. Using an inducible ectopic centromere system that uncouples CENP-A deposition from endogenous centromere function and cell-cycle progression, we demonstrate that CENP-A assembly by its loading factor, CAL1, requires RNAPII-mediated transcription of the underlying DNA. This transcription depends on the CAL1 binding partner FACT, but not on CENP-A incorporation. Our work establishes RNAPII passage as a key step in chaperone-mediated CENP-A chromatin establishment and propagation. PMID- 26151907 TI - Drag of Clean and Fouled Net Panels--Measurements and Parameterization of Fouling. AB - Biofouling is a serious problem in marine aquaculture and it has a number of negative impacts including increased forces on aquaculture structures and reduced water exchange across nets. This in turn affects the behavior of fish cages in waves and currents and has an impact on the water volume and quality inside net pens. Even though these negative effects are acknowledged by the research community and governmental institutions, there is limited knowledge about fouling related effects on the flow past nets, and more detailed investigations distinguishing between different fouling types have been called for. This study evaluates the effect of hydroids, an important fouling organism in Norwegian aquaculture, on the forces acting on net panels. Drag forces on clean and fouled nets were measured in a flume tank, and net solidity including effect of fouling were determined using image analysis. The relationship between net solidity and drag was assessed, and it was found that a solidity increase due to hydroids caused less additional drag than a similar increase caused by change in clean net parameters. For solidities tested in this study, the difference in drag force increase could be as high as 43% between fouled and clean nets with same solidity. The relationship between solidity and drag force is well described by exponential functions for clean as well as for fouled nets. A method is proposed to parameterize the effect of fouling in terms of an increase in net solidity. This allows existing numerical methods developed for clean nets to be used to model the effects of biofouling on nets. Measurements with other types of fouling can be added to build a database on effects of the accumulation of different fouling organisms on aquaculture nets. PMID- 26151906 TI - Selective CNS Uptake of the GCP-II Inhibitor 2-PMPA following Intranasal Administration. AB - Glutamate carboxypeptidase II (GCP-II) is a brain metallopeptidase that hydrolyzes the abundant neuropeptide N-acetyl-aspartyl-glutamate (NAAG) to NAA and glutamate. Small molecule GCP-II inhibitors increase brain NAAG, which activates mGluR3, decreases glutamate, and provide therapeutic utility in a variety of preclinical models of neurodegenerative diseases wherein excess glutamate is presumed pathogenic. Unfortunately no GCP-II inhibitor has advanced clinically, largely due to their highly polar nature resulting in insufficient oral bioavailability and limited brain penetration. Herein we report a non invasive route for delivery of GCP-II inhibitors to the brain via intranasal (i.n.) administration. Three structurally distinct classes of GCP-II inhibitors were evaluated including DCMC (urea-based), 2-MPPA (thiol-based) and 2-PMPA (phosphonate-based). While all showed some brain penetration following i.n. administration, 2-PMPA exhibited the highest levels and was chosen for further evaluation. Compared to intraperitoneal (i.p.) administration, equivalent doses of i.n. administered 2-PMPA resulted in similar plasma exposures (AUC0-t, i.n./AUC0-t, i.p. = 1.0) but dramatically enhanced brain exposures in the olfactory bulb (AUC0-t, i.n./AUC0-t, i.p. = 67), cortex (AUC0-t, i.n./AUC0-t, i.p. = 46) and cerebellum (AUC0-t, i.n./AUC0-t, i.p. = 6.3). Following i.n. administration, the brain tissue to plasma ratio based on AUC0-t in the olfactory bulb, cortex, and cerebellum were 1.49, 0.71 and 0.10, respectively, compared to an i.p. brain tissue to plasma ratio of less than 0.02 in all areas. Furthermore, i.n. administration of 2-PMPA resulted in complete inhibition of brain GCP-II enzymatic activity ex-vivo confirming target engagement. Lastly, because the rodent nasal system is not similar to humans, we evaluated i.n. 2-PMPA also in a non-human primate. We report that i.n. 2-PMPA provides selective brain delivery with micromolar concentrations. These studies support intranasal delivery of 2 PMPA to deliver therapeutic concentrations in the brain and may facilitate its clinical development. PMID- 26151908 TI - SBA-15 Mesoporous Silica Modified with Gallic Acid and Evaluation of Its Cytotoxic Activity. AB - Gallic acid has been covalently conjugated to SBA-15 mesoporous silica surface through different linkers. Cytotoxic activity of the hybrid organic-inorganic systems against HeLa and KB cell lines has been analyzed. Up to 67% of HeLa or KB tumor cells growth inhibition has been achieved at low silica concentration used (10 MUg mL(-1)). PMID- 26151910 TI - Simple indole alkaloids and those with a nonrearranged monoterpenoid unit. AB - This review covers the literature on simple indole alkaloids and those with a nonrearranged monoterpenoid unit from the beginning of 2012 up to the end of 2013, which includes newly isolated alkaloids, structure determinations, total syntheses and biological activities. PMID- 26151909 TI - Silencing of Cholinergic Basal Forebrain Neurons Using Archaerhodopsin Prolongs Slow-Wave Sleep in Mice. AB - The basal forebrain (BF) plays a crucial role in cortical activation. Our previous study showed that activation of cholinergic BF neurons alone is sufficient to suppress slow-wave sleep (SWS) and promote wakefulness and rapid eye-movement (REM) sleep. However, the exact role of silencing cholinergic BF neurons in the sleep-wake cycle remains unclear. We inhibitied the cholinergic BF neurons genetically targeted with archaerhodopsin (Arch) with yellow light to clarify the role of cholinergic BF neurons in the sleep-wake cycle. Bilateral inactivation of cholinergic BF neurons genetically targeted with archaerhodopsin prolonged SWS and decreased the probability of awakening from SWS in mice. However, silencing these neurons changed neither the duration of wakefulness or REM sleep, nor the probability of transitions to other sleep-wake episodes from wakefulness or REM sleep. Furthermore, silencing these neurons for 6 h within the inactive or active period increased the duration of SWS at the expense of the duration of wakefulness, as well as increasing the number of prolonged SWS episodes (120-240 s). The lost wakefulness was compensated by a delayed increase of wakefulness, so the total duration of SWS and wakefulness during 24 h was kept stable. Our results indicate that the main effect of these neurons is to terminate SWS, whereas wakefulness or REM sleep may be determined by co-operation of the cholinergic BF neurons with other arousal-sleep control systems. PMID- 26151912 TI - Vibrationally resolved optical spectra of modified diamondoids obtained from time dependent correlation function methods. AB - Optical properties of modified diamondoids have been studied theoretically using vibrationally resolved electronic absorption, emission and resonance Raman spectra. A time-dependent correlation function approach has been used for electronic two-state models, comprising a ground state (g) and a bright, excited state (e), the latter determined from linear-response, time-dependent density functional theory (TD-DFT). The harmonic and Condon approximations were adopted. In most cases origin shifts, frequency alteration and Duschinsky rotation in excited states were considered. For other cases where no excited state geometry optimization and normal mode analysis were possible or desired, a short-time approximation was used. The optical properties and spectra have been computed for (i) a set of recently synthesized sp(2)/sp(3) hybrid species with C[double bond, length as m-dash]C double-bond connected saturated diamondoid subunits, (ii) functionalized (mostly by thiol or thione groups) diamondoids and (iii) urotropine and other C-substituted diamondoids. The ultimate goal is to tailor optical and electronic features of diamondoids by electronic blending, functionalization and substitution, based on a molecular-level understanding of the ongoing photophysics. PMID- 26151911 TI - Voxel-based morphometry predicts shifts in dendritic spine density and morphology with auditory fear conditioning. AB - Neuroimaging has provided compelling data about the brain. Yet the underlying mechanisms of many neuroimaging techniques have not been elucidated. Here we report a voxel-based morphometry (VBM) study of Thy1-YFP mice following auditory fear conditioning complemented by confocal microscopy analysis of cortical thickness, neuronal morphometric features and nuclei size/density. Significant VBM results included the nuclei of the amygdala, the insula and the auditory cortex. There were no significant VBM changes in a control brain area. Focusing on the auditory cortex, confocal analysis showed that fear conditioning led to a significantly increased density of shorter and wider dendritic spines, while there were no spine differences in the control area. Of all the morphology metrics studied, the spine density was the only one to show significant correlation with the VBM signal. These data demonstrate that learning-induced structural changes detected by VBM may be partially explained by increases in dendritic spine density. PMID- 26151913 TI - MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice. AB - Skeletal muscle stem cells, called satellite cells, are a quiescent heterogeneous population. Their heterogeneity is influenced by Pax7, a well-defined transcriptional regulator of satellite cell functions that defines two subpopulations: Pax7(Hi) and Pax7(Lo). However, the mechanisms by which these subpopulations are established and maintained during myogenesis are not completely understood. Here we show that miR-431, which is predominantly expressed in the skeletal muscle, mediates satellite cell heterogeneity by fine tuning Pax7 levels during muscle development and regeneration. In miR-431 transgenic mice, the Pax7(Lo) subpopulation is enriched, enhances myogenic differentiation and accelerates muscle regeneration. Notably, miR-431 attenuates the muscular dystrophic phenotype in mdx mice and may be a potential therapeutic target in muscular diseases. miR-431 transgenic mice are a unique genetic model for investigating the cellular features and biological functions of Pax7(Lo) satellite cells during muscle development and regeneration. PMID- 26151915 TI - Adult Age Differences in Dual Information Processes: Implications for the Role of Affective and Deliberative Processes in Older Adults' Decision Making. AB - Age differences in affective/experiential and deliberative processes have important theoretical implications for judgment and decision theory and important pragmatic implications for older-adult decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age. However, age-related adaptive processes, including motivated selectivity in the use of deliberative capacity, an increased focus on emotional goals, and greater experience, predict better or worse decisions for older adults depending on the situation. The aim of the current review is to examine adult age differences in affective and deliberative information processes in order to understand their potential impact on judgments and decisions. We review evidence for the role of these dual processes in judgment and decision making and then review two representative life-span perspectives (based on aging-related changes to cognitive or motivational processes) on the interplay between these processes. We present relevant predictions for older-adult decisions and make note of contradictions and gaps that currently exist in the literature. Finally, we review the sparse evidence about age differences in decision making and how theories and findings regarding dual processes could be applied to decision theory and decision aiding. In particular, we focus on prospect theory (Kahneman & Tversky, 1979) and how prospect theory and theories regarding age differences in information processing can inform one another. PMID- 26151914 TI - Evaluation of an X-Ray Dose Profile Derived from an Optically Stimulated Luminescent Dosimeter during Computed Tomographic Fluoroscopy. AB - The purpose of this study was to evaluate scatter radiation dose to the subject surface during X-ray computed tomography (CT) fluoroscopy using the integrated dose ratio (IDR) of an X-ray dose profile derived from an optically stimulated luminescent (OSL) dosimeter. We aimed to obtain quantitative evidence supporting the radiation protection methods used during previous CT fluoroscopy. A multislice CT scanner was used to perform this study. OSL dosimeters were placed on the top and the lateral side of the chest phantom so that the longitudinal direction of dosimeters was parallel to the orthogonal axis-to-slice plane for measurement of dose profiles in CT fluoroscopy. Measurement of fluoroscopic conditions was performed at 120 kVp and 80 kVp. Scatter radiation dose was evaluated by calculating the integrated dose determined by OSL dosimetry. The overall percent difference of the integrated doses between OSL dosimeters and ionization chamber was 5.92%. The ratio of the integrated dose of a 100-mm length area to its tails (-50 to -6 mm, 50 to 6 mm) was the lowest on the lateral side at 80 kVp and the highest on the top at 120 kVp. The IDRs for different measurement positions were larger at 120 kVp than at 80 kVp. Similarly, the IDRs for the tube voltage between the primary X-ray beam and scatter radiation was larger on the lateral side than on the top of the phantom. IDR evaluation suggested that the scatter radiation dose has a high dependence on the position and a low dependence on tube voltage relative to the primary X-ray beam for constant dose rate fluoroscopic conditions. These results provided quantitative evidence supporting the radiation protection methods used during CT fluoroscopy in previous studies. PMID- 26151916 TI - Use It-and Keep It, Longer, Probably: A Reply to Salthouse (2006). AB - In this article, I call into serious question Salthouse's (2006) conclusions evaluating and disparaging the validity of the "use it or lose it" hypothesis regarding mental exercise and mental aging. I do so, in some part, by using data not discussed by Salthouse. The core of my argument relies heavily on a critical assessment of the conclusions that Salthouse derived from both his theoretical reasoning and his review of the literature. The more judicious conclusion I reach is that, although the whole story regarding cognitive function and aging is not known, at some level and to some degree, "using" it often delays the eventuality of "losing" it. PMID- 26151917 TI - Reply to Schooler: Consistent Is Not Conclusive. AB - In this reply, I address the major issues raised by Schooler in his commentary on my article. Although we probably disagree about some points, I suspect that we are in agreement that there is empirical evidence that can be interpreted as being consistent with some aspects of the mental-exercise hypothesis. However, from my perspective, the available evidence is far from conclusive with respect to mental exercise slowing the rate of age-related mental decline, and recognition of the current state of uncertainty on this issue will likely facilitate progress in identifying the role of mental activity and other moderators of mental aging. PMID- 26151918 TI - Emotional Arousal and Memory Binding: An Object-Based Framework. AB - Binding various features of an event together and maintaining these connections in memory is an essential component of episodic memories. Previous theories make contradictory predictions about the effects of emotional arousal on memory binding. In this article, I review evidence for both arousal-impaired and arousal enhanced memory binding and explain these contradictory findings using an object based framework. According to this framework, emotionally arousing objects attract attention that enhances binding of their constituent features. In contrast, the emotional arousal associated with one object either impairs or has no effect on the associations between that object and other distinct objects or background contextual information. After initial encoding, the attention-grabbing nature of emotionally arousing objects can lead to interference in working memory, making it more difficult to maintain other bound representations. These contrasting effects of arousal on memory binding should help predict which aspects of emotional memories are likely to be accurate and which aspects are likely to be misremembered. PMID- 26151919 TI - Psychological Treatments That Cause Harm. AB - The phrase primum non nocere ("first, do no harm") is a well-accepted credo of the medical and mental health professions. Although emerging data indicate that several psychological treatments may produce harm in significant numbers of individuals, psychologists have until recently paid little attention to the problem of hazardous treatments. I critically evaluate and update earlier conclusions regarding deterioration effects in psychotherapy, outline methodological obstacles standing in the way of identifying potentially harmful therapies (PHTs), provide a provisional list of PHTs, discuss the implications of PHTs for clinical science and practice, and delineate fruitful areas for further research on PHTs. A heightened emphasis on PHTs should narrow the scientist practitioner gap and safeguard mental health consumers against harm. Moreover, the literature on PHTs may provide insight into underlying mechanisms of change that cut across many domains of psychotherapy. The field of psychology should prioritize its efforts toward identifying PHTs and place greater emphasis on potentially dangerous than on empirically supported therapies. PMID- 26151920 TI - How Can Measures of Subjective Well-Being Be Used to Inform Public Policy? AB - The debate surrounding the use of subjective measures of well-being for policy purposes has intensified in recent years. Many social scientists are arguing that the time is right for policymakers to extend their traditional focus on material well-being and economic development to include the impact policies have on how people think and feel about their lives. However, policymakers may have many legitimate goals beyond making people happy. In this article, we begin by presenting three archetypal accounts of well-being that policymakers could use to guide policy (mental-state, objective-list, and desire-fulfillment accounts) and discussing some of the normative and methodological limitations of each. We discuss how a subjective (mental-state) approach could be used to aid the achievement of objective-list and desire-fulfillment policy goals. We then consider ways in which a subjective approach may benefit policymakers in its own right, such as by aiding the valuation of hard-to-quantify costs and benefits, providing a standard unit of measurement for comparisons of well-being across domains, and helping to set policy defaults. We conclude with a discussion of some of the remaining measurement issues and general policy implications. PMID- 26151921 TI - Psychologist at Play: Robert P. Abelson's Life and Contributions to Psychological Science. PMID- 26151922 TI - Argon blocks the expression of locomotor sensitization to amphetamine through antagonism at the vesicular monoamine transporter-2 and mu-opioid receptor in the nucleus accumbens. AB - We investigated the effects of the noble gas argon on the expression of locomotor sensitization to amphetamine and amphetamine-induced changes in dopamine release and mu-opioid neurotransmission in the nucleus accumbens. We found (1) argon blocked the increase in carrier-mediated dopamine release induced by amphetamine in brain slices, but, in contrast, potentiated the decrease in KCl-evoked dopamine release induced by amphetamine, thereby suggesting that argon inhibited the vesicular monoamine transporter-2; (2) argon blocked the expression of locomotor and mu-opioid neurotransmission sensitization induced by repeated amphetamine administration in a short-term model of sensitization in rats; (3) argon decreased the maximal number of binding sites and increased the dissociation constant of mu-receptors in membrane preparations, thereby indicating that argon is a mu-receptor antagonist; (4) argon blocked the expression of locomotor sensitization and context-dependent locomotor activity induced by repeated administration of amphetamine in a long-term model of sensitization. Taken together, these data indicate that argon could be of potential interest for treating drug addiction and dependence. PMID- 26151923 TI - Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients. AB - Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C(11)]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker. PMID- 26151924 TI - Serum pro-BDNF/BDNF as a treatment biomarker for response to docosahexaenoic acid in traumatized people vulnerable to developing psychological distress: a randomized controlled trial. AB - Our open-label pilot study showed that supplementation with docosahexaenoic acid (DHA) increased serum brain-derived neurotrophic factor (BDNF) levels and that there might be an association between changes in serum BDNF levels and reduced psychological distress. Animal research has indicated that a DHA-enriched diet increases BDNF in the brain. In this randomized double-blind controlled trial of severely injured patients vulnerable to posttraumatic stress disorder (PTSD) and depression, we examined whether DHA increases serum BDNF levels and whether changes in BDNF levels are associated with subsequent symptoms of PTSD and depression. Patients received 1470 mg per day of DHA plus 147 mg per day of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. Serum levels of mature BDNF and precursor pro-BDNF at baseline and 12-week follow-up were measured using enzyme-linked immunosorbent assay kits. At 12 weeks, we used the Clinician-Administered PTSD Scale to assess PTSD symptoms and depressive symptoms by the Montgomery-Asberg Depression Rating Scale. We found a significant increase in serum BDNF levels during the trial in the DHA and placebo groups with no interaction between time and group. Changes in BDNF levels were not associated with PTSD severity but negatively associated with depression severity (Spearman's rho = -0.257, P = 0.012). Changes in pro-BDNF were also negatively associated with depression severity (Spearman's rho = -0.253, P = 0.013). We found no specific effects of DHA on increased serum levels of BDNF and pro-BDNF; however, evidence in this study suggests that increased BDNF and pro-BDNF have a protective effect by minimizing depression severity. PMID- 26151925 TI - Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder: a positron emission tomography study with [11C]GR205171. AB - The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n = 17) and healthy controls (n = 17) using positron emission tomography and the radiotracer [11C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders. PMID- 26151926 TI - Genetics of rapid eye movement sleep in humans. AB - The trait-like nature of electroencephalogram (EEG) is well established. Furthermore, EEG of wake and non-rapid eye movement (non-REM) sleep has been shown to be highly heritable. However, the genetic effects on REM sleep EEG microstructure are as yet unknown. REM sleep is of special interest since animal and human data suggest a connection between REM sleep abnormalities and the pathophysiology of psychiatric and neurological diseases. Here we report the results of a study in monozygotic (MZ) and dizygotic (DZ) twins examining the heritability of REM sleep EEG. We studied the architecture, spectral composition and phasic parameters of REM sleep and identified genetic effects on whole investigated EEG frequency spectrum as well as phasic REM parameters (REM density, REM activity and organization of REMs in bursts). In addition, cluster analysis based on the morphology of the EEG frequency spectrum revealed that the similarity among MZ twins is close to intra-individual stability. The observed strong genetic effects on REM sleep characteristics establish REM sleep as an important source of endophenotypes for psychiatric and neurological diseases. PMID- 26151928 TI - Correction: Emerging approaches for the synthesis of triazoles: beyond metal catalyzed and strain-promoted azide-alkyne cycloaddition. AB - Correction for 'Emerging approaches for the synthesis of triazoles: beyond metal catalyzed and strain-promoted azide-alkyne cycloaddition' by Carolina G. S. Lima et al., Chem. Commun., 2015, 51, 10784-10796. PMID- 26151927 TI - The Influence of Hearing Aid Use on Outcomes of Children With Mild Hearing Loss. AB - PURPOSE: This study examined the effects of consistent hearing aid (HA) use on outcomes in children with mild hearing loss (HL). METHOD: Five- or 7-year-old children with mild HL were separated into 3 groups on the basis of patterns of daily HA use. Using analyses of variance, we compared outcomes between groups on speech and language tests and a speech perception in noise task. Regression models were used to investigate the influence of cumulative auditory experience (audibility, early intervention, HA use) on outcomes. RESULTS: Full-time HA users demonstrated significantly higher scores on vocabulary and grammar measures compared with nonusers. There were no significant differences between the 3 groups on articulation or speech perception measures. After controlling for the variance in age at confirmation of HL, level of audibility, and enrollment in early intervention, only amount of daily HA use was a significant predictor of grammar and vocabulary. CONCLUSIONS: The current results provide evidence that children's language development benefits from consistent HA use. Nonusers are at risk in areas such as vocabulary and grammar compared with other children with mild HL who wear HAs regularly. Service providers should work collaboratively to encourage consistent HA use. PMID- 26151930 TI - Combined Single Neuron Unit Activity and Local Field Potential Oscillations in a Human Visual Recognition Memory Task. AB - GOAL: Activities of neuronal networks range from action potential firing of individual neurons, coordinated oscillations of local neuronal assemblies, and distributed neural populations. Here, we describe recordings using hybrid electrodes, containing both micro- and clinical macroelectrodes, to simultaneously sample both large-scale network oscillations and single neuron spiking activity in the medial temporal lobe structures of human subjects during a visual recognition memory task. We quantify and compare single neuron unit activity (SUA) with high-frequency macrofield oscillations (HFOs) for decoding visual images. RESULTS: SUA and HFOs were recorded using hybrid electrodes containing both micro and macroelectrode contacts, implanted in patients with focal epilepsy. Decoding of image properties in different task trials was performed, analyzing SUA and HFO as point processes to capture the dynamics of neurons and their assemblies at different spatiotemporal scales, ranging from submillisecond discharges of single units to fast oscillations across large neuronal populations. Results highlight the limitations and potential complementary use of SUA and HFOs for decoding of general image properties. CONCLUSION: The dynamics of SUA and HFOs can be used to explore a wide range of neuronal assembly activities engaged in human memory processing. SIGNIFICANCE: Hybrid electrodes provide a technological bridge for exploring multiscale activity, spanning individual neurons, their assemblies, and large-scale population activity reflected in local field potentials. Analysis of SUA and HFO dynamics as point processes provides a potentially useful signal processing method for exploring the neuronal correlates operating at different spatial scales. PMID- 26151929 TI - Association between Maternal Depression Symptoms across the First Eleven Years of Their Child's Life and Subsequent Offspring Suicidal Ideation. AB - Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child's life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19, 4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis. PMID- 26151931 TI - Computational Study Toward Deep Transcranial Magnetic Stimulation Using Coaxial Circular Coils. AB - OBJECTIVE: To investigate the possibility for stimulating deeper brain regions while decreasing the electrical field in superficial cortical regions by employing coaxial circular coils. METHODS: The Halo coil, Halo-circular assembly coil (HCA coil) and Halo coil working with two circular coils (HTC coil) were applied over a 36-tissue anatomically based head model. Three-dimensional distributions of magnetic flux density, induced electric field in head tissues were obtained by 3-D impedance method. RESULTS: For the case of HCA coil with current flowing in the same direction in each of two coils, the field penetration depth by the conventional circular coil can be effectively increased at the expense of reduced focality. For the case of the HTC coil with currents flowing in opposite direction in the neighboring coils, overthreshold electric fields can be produced in deep brain regions, while the subthreshold fields were produced in superficial cortical areas. CONCLUSION: The HTC coil with varied coil parameters and different injected currents provides a flexible way for deep brain stimulation with better ratio of deep region field relative to field at the shallow areas. SIGNIFICANCE: The HTC coil is promising for deep transcranial magnetic stimulation, which may offer a new tool with potential for both research and clinical applications for psychiatric and neurological disorders associated with dysfunctions of deep brain regions. PMID- 26151933 TI - Simultaneous Multi-Structure Segmentation and 3D Nonrigid Pose Estimation in Image-Guided Robotic Surgery. AB - In image-guided robotic surgery, segmenting the endoscopic video stream into meaningful parts provides important contextual information that surgeons can exploit to enhance their perception of the surgical scene. This information provides surgeons with real-time decision-making guidance before initiating critical tasks such as tissue cutting. Segmenting endoscopic video is a challenging problem due to a variety of complications including significant noise attributed to bleeding and smoke from cutting, poor appearance contrast between different tissue types, occluding surgical tools, and limited visibility of the objects' geometries on the projected camera views. In this paper, we propose a multi-modal approach to segmentation where preoperative 3D computed tomography scans and intraoperative stereo-endoscopic video data are jointly analyzed. The idea is to segment multiple poorly visible structures in the stereo/multichannel endoscopic videos by fusing reliable prior knowledge captured from the preoperative 3D scans. More specifically, we estimate and track the pose of the preoperative models in 3D and consider the models' non-rigid deformations to match with corresponding visual cues in multi-channel endoscopic video and segment the objects of interest. Further, contrary to most augmented reality frameworks in endoscopic surgery that assume known camera parameters, an assumption that is often violated during surgery due to non-optimal camera calibration and changes in camera focus/zoom, our method embeds these parameters into the optimization hence correcting the calibration parameters within the segmentation process. We evaluate our technique on synthetic data, ex vivo lamb kidney datasets, and in vivo clinical partial nephrectomy surgery with results demonstrating high accuracy and robustness. PMID- 26151932 TI - Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State. AB - Human embryonic stem cells (hESCs) undergo epigenetic changes in vitro which may compromise function, so an epigenetic pluripotency "signature" would be invaluable for line validation. We assessed Cytosine-phosphate-Guanine Island (CGI) methylation in hESCs by genomic DNA hybridisation to a CGI array, and saw substantial variation in CGI methylation between lines. Comparison of hESC CGI methylation profiles to corresponding somatic tissue data and hESC mRNA expression profiles identified a conserved hESC-specific methylation pattern associated with expressed genes. Transcriptional repressors and activators were over-represented amongst genes whose associated CGIs were methylated or unmethylated specifically in hESCs, respectively. Knockdown of candidate transcriptional regulators (HMGA1, GLIS2, PFDN5) induced differentiation in hESCs, whereas ectopic expression in fibroblasts modulated iPSC colony formation. Chromatin immunoprecipitation confirmed interaction between the candidates and the core pluripotency transcription factor network. We thus identify novel pluripotency genes on the basis of a conserved and distinct epigenetic configuration in human stem cells. PMID- 26151934 TI - Functional Characterization of the Receiver Domain for Phosphorelay Control in Hybrid Sensor Kinases. AB - Hybrid sensor kinase, which contains a histidine kinase (HK) domain, a receiver domain, and a histidine-containing phosphotransmitter (HPt) domain, conveys signals to its cognate response regulator by means of a His-Asp-His-Asp phosphorelay. We examined the multistep phosphorelay of a recombinant EvgAS system in Escherichia coli and performed in vitro quantitative analyses of phosphorylation by using Phos-tag SDS-PAGE. Replacement of Asp in the receiver domain of EvgS by Ala markedly promoted phosphorylation at His in the HK domain compared with that in wild-type EvgS. Similar Ala-substituted mutants of other hybrid sensor kinases BarA and ArcB showed similar characteristics. In the presence of sufficient ATP, autophosphorylation of the HK domain in the mutant progressed efficiently with nearly pseudo-first-order kinetics until the phosphorylation ratio reached a plateau value of more than 95% within 60 min, and the value was maintained until 180 min. However, both wild-type EvgS and the Ala substituted mutant of His in the HPt domain showed a phosphorylation ratio of less than 25%, which gradually decreased after 10 min. These results showed that the phosphorylation level is regulated negatively by the receiver domain. Furthermore, our in vivo assays confirmed the existence of a similar hyperphosphorylation reaction in the HK domain of the EvgS mutant in which the Asp residue was replaced with Ala, confirming the validity of the control mechanism proposed from profiling of phosphorylation in vitro [corrected]. PMID- 26151936 TI - Hierarchical Grid-based Multi-People Tracking-by-Detection With Global Optimization. AB - We present a hierarchical grid-based, globally optimal tracking-by-detection approach to track an unknown number of targets in complex and dense scenarios, particularly addressing the challenges of complex interaction and mutual occlusion. Frame-by-frame detection is performed by hierarchical likelihood grids, matching shape templates through a fast oriented distance transform. To allow recovery from misdetections, common heuristics such as nonmaxima suppression within observations is eschewed. Within a discretized state-space, the data association problem is formulated as a grid-based network flow model, resulting in a convex problem casted into an integer linear programming form, giving a global optimal solution. In addition, we show how a behavior cue (body orientation) can be integrated into our association affinity model, providing valuable hints for resolving ambiguities between crossing trajectories. Unlike traditional motion-based approaches, we estimate body orientation by a hybrid methodology, which combines the merits of motion-based and 3D appearance-based orientation estimation, thus being capable of dealing also with still-standing or slowly moving targets. The performance of our method is demonstrated through experiments on a large variety of benchmark video sequences, including both indoor and outdoor scenarios. PMID- 26151935 TI - Comparative Genomic Analysis of Asian Haemorrhagic Septicaemia-Associated Strains of Pasteurella multocida Identifies More than 90 Haemorrhagic Septicaemia Specific Genes. AB - Pasteurella multocida is the primary causative agent of a range of economically important diseases in animals, including haemorrhagic septicaemia (HS), a rapidly fatal disease of ungulates. There is limited information available on the diversity of P. multocida strains that cause HS. Therefore, we determined draft genome sequences of ten disease-causing isolates and two vaccine strains and compared these genomes using a range of bioinformatic analyses. The draft genomes of the 12 HS strains were between 2,298,035 and 2,410,300 bp in length. Comparison of these genomes with the North American HS strain, M1404, and other available P. multocida genomes (Pm70, 3480, 36950 and HN06) identified a core set of 1,824 genes. A set of 96 genes was present in all HS isolates and vaccine strains examined in this study, but absent from Pm70, 3480, 36950 and HN06. Moreover, 59 genes were shared only by the Asian B:2 strains. In two Pakistani isolates, genes with high similarity to genes in the integrative and conjugative element, ICEPmu1 from strain 36950 were identified along with a range of other antimicrobial resistance genes. Phylogenetic analysis indicated that the HS strains formed clades based on their country of isolation. Future analysis of the 96 genes unique to the HS isolates will aid the identification of HS-specific virulence attributes and facilitate the development of disease-specific diagnostic tests. PMID- 26151937 TI - Angular-Similarity-Preserving Binary Signatures for Linear Subspaces. AB - We propose a similarity-preserving binary signature method for linear subspaces. In computer vision and pattern recognition, linear subspace is a very important representation for many kinds of data, such as face images, action and gesture videos, and so on. When there is a large amount of subspace data and the ambient dimension is high, the cost of computing the pairwise similarity between the subspaces would be high and it requires a large storage space for storing the subspaces. In this paper, we first define the angular similarity and angular distance between the subspaces. Then, based on this similarity definition, we develop a similarity-preserving binary signature method for linear subspaces, which transforms a linear subspace into a compact binary signature, and the Hamming distance between two signatures provides an unbiased estimate of the angular similarity between the two subspaces. We also provide a lower bound of the signature length sufficient to guarantee uniform distance-preservation between every pair of subspaces in a set. Experiments on face recognition, gesture recognition, and action recognition verify the effectiveness of the proposed method. PMID- 26151938 TI - Manifold Kernel Sparse Representation of Symmetric Positive-Definite Matrices and Its Applications. AB - The symmetric positive-definite (SPD) matrix, as a connected Riemannian manifold, has become increasingly popular for encoding image information. Most existing sparse models are still primarily developed in the Euclidean space. They do not consider the non-linear geometrical structure of the data space, and thus are not directly applicable to the Riemannian manifold. In this paper, we propose a novel sparse representation method of SPD matrices in the data-dependent manifold kernel space. The graph Laplacian is incorporated into the kernel space to better reflect the underlying geometry of SPD matrices. Under the proposed framework, we design two different positive definite kernel functions that can be readily transformed to the corresponding manifold kernels. The sparse representation obtained has more discriminating power. Extensive experimental results demonstrate good performance of manifold kernel sparse codes in image classification, face recognition, and visual tracking. PMID- 26151939 TI - Optimized Kaiser-Bessel Window Functions for Computed Tomography. AB - Kaiser-Bessel window functions are frequently used to discretize tomographic problems because they have two desirable properties: 1) their short support leads to a low computational cost and 2) their rotational symmetry makes their imaging transform independent of the direction. In this paper, we aim at optimizing the parameters of these basis functions. We present a formalism based on the theory of approximation and point out the importance of the partition-of-unity condition. While we prove that, for compact-support functions, this condition is incompatible with isotropy, we show that minimizing the deviation from the partition of unity condition is highly beneficial. The numerical results confirm that the proposed tuning of the Kaiser-Bessel window functions yields the best performance. PMID- 26151940 TI - The L0 Regularized Mumford-Shah Model for Bias Correction and Segmentation of Medical Images. AB - We propose a new variant of the Mumford-Shah model for simultaneous bias correction and segmentation of images with intensity inhomogeneity. First, based on the model of images with intensity inhomogeneity, we introduce an L0 gradient regularizer to model the true intensity and a smooth regularizer to model the bias field. In addition, we derive a new data fidelity using the local intensity properties to allow the bias field to be influenced by its neighborhood. Second, we use a two-stage segmentation method, where the fast alternating direction method is implemented in the first stage for the recovery of true intensity and bias field and a simple thresholding is used in the second stage for segmentation. Different from most of the existing methods for simultaneous bias correction and segmentation, we estimate the bias field and true intensity without fixing either the number of the regions or their values in advance. Our method has been validated on medical images of various modalities with intensity inhomogeneity. Compared with the state-of-art approaches and the well-known brain software tools, our model is fast, accurate, and robust with initializations. PMID- 26151941 TI - Employing TDMA Protocol in Neural Nanonetworks in Case of Neuron Specific Faults. AB - Many neurodegenerative diseases arise from the malfunctioning neurons in the pathway where the signal is carried. In this paper, we propose neuron specific TDMA/multiplexing and demultiplexing mechanisms to convey the spikes of a receptor neuron over a neighboring path in case of an irreversible path fault existing in its original path. The multiplexing mechanism depends on neural delay box (NDB) which is composed of a relay unit and a buffering unit. The relay unit can be realized as a nanoelectronic device. The buffering unit can be implemented either via neural delay lines as employed in optical switching systems or via nanoelectronic delay lines, i.e., delay flip flops. Demultiplexing is realized by a demultiplexer unit according to the time slot assignment information. Besides, we propose the use of neural interfaces in the NDBs and the demultiplexer unit for detecting and stimulating the generation of spikes. The objective of the proposed mechanisms is to substitute a malfunctioning path, increase the number of spikes delivered and correctly deliver the spikes to the intended part of the somatosensory cortex. The results demonstrate that significant performance improvement on the successively delivered number of spikes is achievable when delay lines are employed as neural buffers in NDBs. PMID- 26151942 TI - Bioorthogonal labelling of living bacteria using unnatural amino acids containing nitrones and a nitrone derivative of vancomycin. AB - Unnatural D-amino acids bearing endocyclic nitrones were developed for live-cell labelling of the bacterial peptidoglycan layer. Metabolic incorporation of D-Lys and D-Ala derivatives bearing different endocyclic nitrones was observed in E. coli, L. innocua, and L. lactis. The incorporated nitrones of these bacteria then rapidly underwent strain-promoted alkyne-nitrone cycloaddition (SPANC) reactions affording chemically modified bacteria. PMID- 26151943 TI - Correction: "On-the-fly" coupled cluster path-integral molecular dynamics: impact of nuclear quantum effects on the protonated water dimer. PMID- 26151944 TI - Development of a self-healing soft pneumatic actuator: a first concept. AB - Inspired by the intrinsic softness and the corresponding embodied intelligence principles, soft pneumatic actuators (SPA) have been developed, which ensure safe interaction in unstructured, unknown environments. Due to their intrinsic softness, these actuators have the ability to resist large mechanical impacts. However, the soft materials used in these structures are in general susceptible to damage caused by sharp objects found in the unstructured environments. This paper proposes to integrate a self-healing (SH-) mechanism in SPAs, such that cuts, tears and perforations in the actuator can be self-healed. Diels-Alder (DA ) polymers, covalent polymer network systems based on the thermoreversible DA reaction, were selected and their mechanical, as well as SH-properties, are described. To evaluate the feasibility of developing an SPA constructed out of SH material, a single cell prototype, a SH-soft pneumatic cell (SH-SPC), was constructed entirely out of DA-polymers. Exploiting the SH-property of the DA polymers, a completely new shaping process is presented in this paper, referred to as 'shaping through folding and self-healing'. 3D polygon structures, like the cubic SH-SPC, can be constructed by folding SH-polymer sheet. The sides of the structures can be sealed and made airtight using a SH-procedure at relatively low temperatures (<90 degrees C). Both the (thermo) mechanical and SH-properties of the SH-SPC prototype were experimentally validated and showed excellent performances. Macroscopic incisions in the prototype were completely healed using a SH-procedure (<70 degrees C). Starting from this single-cell prototype, it is straight-forward to develop a multi-cell prototype, the first SPA ever built completely out of SH-polymers. PMID- 26151945 TI - A Maximum Margin Approach for Semisupervised Ordinal Regression Clustering. AB - Ordinal regression (OR) is generally defined as the task where the input samples are ranked on an ordinal scale. OR has found a wide variety of applications, and a great deal of work has been done on it. However, most of the existing work focuses on supervised/semisupervised OR classification, and the semisupervised OR clustering problems have not been explicitly addressed. In real-world OR applications, labeling a large number of training samples is usually time consuming and costly, and instead, a set of unlabeled samples can be utilized to set up the OR model. Moreover, although the sample labels are unavailable, we can sometimes get the relative ranking information of the unlabeled samples. This sample ranking information can be utilized to refine the OR model. Hence, how to build an OR model on the unlabeled samples and incorporate the sample ranking information into the process of improving the clustering accuracy remains a key challenge for OR applications. In this paper, we consider the semisupervised OR clustering problems with sample-ranking constraints, which give the relative ranking information of the unlabeled samples, and put forward a maximum margin approach for semisupervised OR clustering ( [Formula: see text]SORC). On one hand, [Formula: see text]SORC seeks a set of parallel hyperplanes to partition the unlabeled samples into clusters. On the other hand, a loss function is put forward to incorporate the sample ranking information into the clustering process. As a result, the optimization function of [Formula: see text]SORC is formulated to maximize the margins of the closest neighboring clusters and meanwhile minimize the loss associated with the sample-ranking constraints. Extensive experiments on OR data sets show that the proposed [Formula: see text]SORC method outperforms the traditional semisupervised clustering methods considered. PMID- 26151946 TI - Dutch Translation and Psychometric Testing of the 9-Item Shared Decision Making Questionnaire (SDM-Q-9) and Shared Decision Making Questionnaire-Physician Version (SDM-Q-Doc) in Primary and Secondary Care. AB - PURPOSE: The SDM-Q-9 and SDM-Q-Doc measure patient and physician perception of the extent of shared decision making (SDM) during a physician-patient consultation. So far, no self-report instrument for SDM was available in Dutch, and validation of the scales in other languages has been limited. The aim of this study was to translate both scales into Dutch and assess their psychometric characteristics. METHODS: Participants were patients and their treating physicians (general practitioners and medical specialists). Patients (N = 182) rated their consultation using the SDM-Q-9, 43 physicians rated their consultations using the SDM-Q-Doc (N = 201). Acceptability, reliability (internal consistency), and the factorial structure of the instruments were determined. For convergent validity the CPSpost was used. RESULTS: Reliabilities of both scales were high (alpha SDM-Q-9 0.88; SDM-Q-Doc 0.87). The SDM-Q-9 and SDM-Q-Doc total scores correlated as expected with the CPSpost (SDM-Q-9: r = 0.29; SDM-Q-Doc: r = 0.48) and were significantly different between the CPSpost categories, with lowest mean scores when the physician made the decision alone. Principal Component Analyses showed a two-component model for each scale. A confirmatory factor analysis yielded a mediocre, but acceptable, one-factor model, if Item 1 was excluded; for both scales the best indices of fit were obtained for a one factor solution, if both Items 1 and 9 were excluded. CONCLUSION: The Dutch SDM-Q 9 and SDM-Q-Doc demonstrate good acceptance and reliability; they correlated as expected with the CPSpost and are suitable for use in Dutch primary and specialised care. Although the best model fit was found when excluding Items 1 and 9, we believe these items address important aspects of SDM. Therefore, also based on the coherence with theory and comparability with other studies, we suggest keeping all nine items of the scale. Further research on the SDM-concept in patients and physicians, in different clinical settings and different countries, is necessary to gain a better understanding of the SDM-construct and its measurement. PMID- 26151947 TI - Feasibility Study of a New Method for Low-Complexity Fetal Movement Detection From Abdominal ECG Recordings. AB - Fetal movement counting can provide valuable information on the fetal health, as a strong decrease in the number of movements can be seen as a precursor to fetal death. Typically, assessment of fetal health by fetal movement counting relies on the maternal perception of fetal activity. The percentage of detected movements is strongly subject dependent and with undivided attention of the mother varies between 37% and 88%. Various methods to assist in fetal movement detection exist based on a wide spectrum of measurement techniques. However, these are unsuitable for ambulatory or long-term observation. In this paper, a novel low-complexity method for fetal movement detection is presented based on amplitude and shape changes in the abdominally recorded fetal ECG. This method was compared to a state-of-the-art method from the literature. Using ultrasound-based movement annotations as ground truth, the presented method outperforms the state-of-the art abdominal-ECG based method, with a sensitivity, specificity, and accuracy of 56%, 68%, and 63%, respectively. Additionally, a significant reduction in algorithm complexity is achieved, possibly enabling continuous ambulatory fetal movement detection and early detection of reduced fetal motility. PMID- 26151948 TI - Pairwise Constraint-Guided Sparse Learning for Feature Selection. AB - Feature selection aims to identify the most informative features for a compact and accurate data representation. As typical supervised feature selection methods, Lasso and its variants using L1-norm-based regularization terms have received much attention in recent studies, most of which use class labels as supervised information. Besides class labels, there are other types of supervised information, e.g., pairwise constraints that specify whether a pair of data samples belong to the same class (must-link constraint) or different classes (cannot-link constraint). However, most of existing L1-norm-based sparse learning methods do not take advantage of the pairwise constraints that provide us weak and more general supervised information. For addressing that problem, we propose a pairwise constraint-guided sparse (CGS) learning method for feature selection, where the must-link and the cannot-link constraints are used as discriminative regularization terms that directly concentrate on the local discriminative structure of data. Furthermore, we develop two variants of CGS, including: 1) semi-supervised CGS that utilizes labeled data, pairwise constraints, and unlabeled data and 2) ensemble CGS that uses the ensemble of pairwise constraint sets. We conduct a series of experiments on a number of data sets from University of California-Irvine machine learning repository, a gene expression data set, two real-world neuroimaging-based classification tasks, and two large-scale attribute classification tasks. Experimental results demonstrate the efficacy of our proposed methods, compared with several established feature selection methods. PMID- 26151949 TI - Identifying (Quasi) Equally Informative Subsets in Feature Selection Problems for Classification: A Max-Relevance Min-Redundancy Approach. AB - An emerging trend in feature selection is the development of two-objective algorithms that analyze the tradeoff between the number of features and the classification performance of the model built with these features. Since these two objectives are conflicting, a typical result stands in a set of Pareto efficient subsets, each having a different cardinality and a corresponding discriminating power. However, this approach overlooks the fact that, for a given cardinality, there can be several subsets with similar information content. The study reported here addresses this problem, and introduces a novel multiobjective feature selection approach conceived to identify: 1) a subset that maximizes the performance of a given classifier and 2) a set of subsets that are quasi equally informative, i.e., have almost same classification performance, to the performance maximizing subset. The approach consists of a wrapper [Wrapper for Quasi Equally Informative Subset Selection (W-QEISS)] built on the formulation of a four-objective optimization problem, which is aimed at maximizing the accuracy of a classifier, minimizing the number of features, and optimizing two entropy based measures of relevance and redundancy. This allows conducting the search in a larger space, thus enabling the wrapper to generate a large number of Pareto efficient solutions. The algorithm is compared against the mRMR algorithm, a two objective wrapper and a computationally efficient filter [Filter for Quasi Equally Informative Subset Selection (F-QEISS)] on 24 University of California, Irvine, (UCI) datasets including both binary and multiclass classification. Experimental results show that W-QEISS has the capability of evolving a rich and diverse set of Pareto-efficient solutions, and that their availability helps in: 1) studying the tradeoff between multiple measures of classification performance and 2) understanding the relative importance of each feature. The quasi equally informative subsets are identified at the cost of a marginal increase in the computational time thanks to the adoption of Borg Multiobjective Evolutionary Algorithm and Extreme Learning Machine as global optimization and learning algorithms, respectively. PMID- 26151950 TI - Thyroid Antagonists (Perchlorate, Thiocyanate, and Nitrate) and Childhood Growth in a Longitudinal Study of U.S. Girls. AB - BACKGROUND: Perchlorate, thiocyanate, and nitrate are sodium/iodide symporter (NIS) inhibitors that block iodide uptake into the thyroid, thus affecting thyroid function. Thyroid dysfunction can adversely affect somatic growth and development in children. To our knowledge, no studies have examined effects of NIS inhibitors on body size measures. OBJECTIVE: We investigated associations between NIS inhibitors and childhood growth in 940 girls from the Puberty Study of the Breast Cancer and Environment Research Program. METHODS: Urine samples collected from girls 6-8 years of age at enrollment (2004-2007) from New York City, greater Cincinnati, Ohio, and the Bay Area in California were analyzed for NIS inhibitors and creatinine (C). The longitudinal association between NIS inhibitors and anthropometric measures [height, waist circumference, and body mass index (BMI)] during at least three visits was examined using mixed effects linear models, adjusted for race and site. RESULTS: Compared with girls in the low-exposure group (3.6, 626, and 500 mg/gC, median perchlorate, thiocyanate, and nitrate, respectively) girls with the highest NIS inhibitor exposure (9.6, 2,343, and 955 mg/gC, median perchlorate, thiocyanate, and nitrate, respectively) had slower growth in waist circumference and BMI but not height. Significant differences in the predicted mean waist circumference and BMI between the low- and high-exposure groups were observed beginning at 11 years of age. CONCLUSIONS: Higher NIS inhibitor exposure biomarkers were associated with reductions in waist circumference and BMI. These findings underscore the need to assess exposure to NIS inhibitors with respect to their influence on childhood growth. CITATION: Mervish NA, Pajak A, Teitelbaum SL, Pinney SM, Windham GC, Kushi LH, Biro FM, Valentin-Blasini L, Blount BC, Wolff MS, for the Breast Cancer and Environment Research Project (BCERP). 2016. Thyroid antagonists (perchlorate, thiocyanate, and nitrate) and childhood growth in a longitudinal study of U.S. girls. Environ Health Perspect 124:542-549; http://dx.doi.org/10.1289/ehp.1409309. PMID- 26151951 TI - Traffic-Related Air Pollution and Parkinson's Disease in Denmark: A Case-Control Study. AB - BACKGROUND: Very little is currently known about air pollutants' adverse effects on neurodegenerative diseases even though recent studies have linked particulate exposures to brain pathologies associated with Parkinson's and Alzheimer's disease. OBJECTIVE: In the present study, we investigated long-term exposure to traffic-related air pollution and Parkinson's disease. METHODS: In a case-control study of 1,696 Parkinson's disease (PD) patients identified from Danish hospital registries and diagnosed 1996-2009 and 1,800 population controls matched by sex and year of birth, we assessed long-term traffic-related air pollutant exposures (represented by nitrogen dioxide; NO2) from a dispersion model, using residential addresses from 1971 to the date of diagnosis or first cardinal symptom for cases and the corresponding index date for their matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for matching factors and potential confounders. RESULTS: We found ambient air pollution from traffic sources to be associated with risk of PD, with a 9% higher risk (95% CI: 3, 16.0%) per interquartile range increase (2.97 MUg/m(3)) in modeled NO2. For participants living for >= 20 years in the capital city, ORs were larger (OR = 1.21; 95% CI: 1.11, 1.31) than in provincial towns (OR = 1.10; 95% CI: 0.97, 1.26), whereas there was no association among rural residents. CONCLUSIONS: Our findings raise concerns about potential effects of air pollution from traffic and other sources on the risk of PD, particularly in populations with high or increasing exposures. PMID- 26151953 TI - First Lotus aortic valve-in-valve implantation to treat degenerated Mitroflow bioprostheses. AB - AIMS: Transcatheter aortic valve-in-valve implantation is an emerging alternative to conventional surgical aortic valve replacement (SAVR) in patients with degenerated aortic bioprostheses. This procedure presents a high risk of coronary occlusion, especially during treatment of patients implanted with a bioprosthesis with a lower distance between the leaflets and the coronary ostia, such as the Mitroflow valve (Sorin S.p.A., Milan, Italy). In this report we aim to describe the safety and feasibility of transfemoral valve-in-valve implantation of a new generation LotusTM Aortic Valve Replacement System (Boston Scientific, Marlborough, MA, USA) in a case of degenerated Mitroflow bioprostheses. METHODS AND RESULTS: We describe a case of degenerated Sorin Mitroflow bioprostheses successfully treated with the transfemoral new-generation Lotus valve-in-valve system. During the procedure no coronary protection was required and the patient had no MACE at 30-day follow-up. To our knowledge, this is the first report of a Lotus valve implant in a degenerated Mitroflow prosthesis. CONCLUSIONS: The transcatheter valve-in-valve procedure using the new-generation Lotus Valve System is a safe and feasible alternative to repeat cardiac surgery in high-risk patients with surgical degenerated Mitroflow bioprostheses. PMID- 26151952 TI - Effects of Arsenite Exposure during Fetal Development on Energy Metabolism and Susceptibility to Diet-Induced Fatty Liver Disease in Male Mice. AB - BACKGROUND: Chronic exposure to arsenicals at various life stages and across a range of exposures has been implicated in cardiometabolic and liver disease, but disease predisposition from developmental exposures remains unclear. OBJECTIVES: In utero and post-weaning exposure to trivalent arsenic (AsIII) was examined on the background of a Western-style diet to determine whether AsIII exposure affects metabolic disease. METHODS: Male Swiss Webster mice were exposed to 100 ppb AsIII in utero, after weaning, or both. Ad libitum access to a Western-style diet was provided after weaning, and the plasma metabolome, liver histopathology, liver enzyme activity, and gene expression were analyzed. RESULTS: Hepatic lipid composition and histopathology revealed that developmental AsIII exposure exacerbated Western-style diet-induced fatty liver disease. Continuous AsIII exposure increased cardiometabolic risk factors including increased body weight, insulin resistance, hyperglycemia, and plasma triglycerides. AsIII exposure produced a decrease in the intermediates of glycolysis and the TCA cycle while increasing ketones. Hepatic isocitrate dehydrogenase activity was also decreased, which confirmed disruption of the TCA cycle. Developmental AsIII exposure increased the expression of genes involved in fatty acid synthesis, lipogenesis, inflammation, and packaging of triglycerides, suggesting an increased acetyl coenzyme A (acetyl-CoA) load. CONCLUSIONS: In utero and continuous early-life exposure to AsIII disrupted normal metabolism and elevated the risk for fatty liver disease in mice maintained on a high-fat diet. Our findings suggest that individuals exposed to AsIII during key developmental periods and who remain exposed to AsIII on the background of a Western-style diet may be at increased risk for metabolic disease later in life. PMID- 26151954 TI - Bioabsorbable vascular scaffold overexpansion: insights from in vitro post expansion experiments. AB - AIMS: While bioresorbable vascular scaffolds (BVS) are increasingly used in clinical practice, their behaviour when post-dilated beyond their recommended maximum overexpansion diameter remains sparsely documented. We aimed to test the overexpansion of the BVS scaffold in vitro and evaluate the impact of excessive scaffold oversizing on focal point support. METHODS AND RESULTS: We examined the post-expansion behaviour of the bioresorbable vascular scaffold (3.0 mm and 3.5 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) after overexpansion with non-compliant (NC) balloons of increasing diameters. After each oversizing step, the scaffolds were measured and inspected for strut disruption using microscope and optical coherence tomography imaging. Point force mechanical measurements on single scaffold struts were also performed to evaluate the impact of excessive scaffold overstretching on focal mechanical support. 3.0 mm and 3.5 mm scaffold sizes could be post-expanded up to 1 mm above their nominal diameters without any strut fracture when deployed without an external constraining model. Importantly, when overexpansion of both scaffold sizes was repeated using a constraining silicone lesion model, only post-expansion with an NC balloon size 0.5 mm larger than the scaffold nominal sizes could be performed without strut fractures. Point force compression analysis on single struts shows that overstretched struts with fractures provided lower focal strength compared to overexpanded ring segments without fractures and normal segments expanded at nominal pressure. CONCLUSIONS: In our experiments, only overexpansion with an NC balloon 0.5 mm larger than the BVS size was feasible for BVS deployed inside an arterial lesion model. Overexpansion of the BVS scaffold beyond recommended post-dilation limits can lead to strut disconnections and focal loss of mechanical support. PMID- 26151955 TI - Motivations for and barriers to choosing an interventional cardiology career path: results from the EAPCI Women Committee worldwide survey. AB - AIMS: Very few women become interventional cardiologists, although a substantial proportion of cardiologists and the majority of medical students are women. In accordance with the EAPCI Women Committee mission of attaining gender equality at the professional level, a worldwide survey was recently conducted aiming to understand better the motivations and the barriers for women in selecting interventional cardiology (IC) as a career path. METHODS AND RESULTS: A total of 1,787 individuals (60.7% women) responded to the survey. Women compared to men were less frequently married (women vs. men, 57.0% vs. 79.8%, p<0.001) and more frequently childless (46.6% vs. 20.5%, p<0.002). The most prevalent reason for choosing IC was passion (83.3% vs. 76.1%, p=0.12), while those for not choosing were, sequentially, lack of opportunity (29.0% vs. 45.7%), radiation concerns (19.9% vs. 11.6%) and preference (16.2% vs. 29.5%), p<0.001. According to 652 men replying to why, in their opinion, women do not choose IC, on-calls and long working hours were the most frequent reasons (35.3%). CONCLUSIONS: Several barriers preclude women from choosing IC, including lack of opportunity, concerns regarding radiation exposure and the prejudices of their male colleagues. This highlights the need to develop new strategies for future training, education, and support of women in order to choose IC. PMID- 26151956 TI - Social Neuroscience: Progress and Implications for Mental Health. AB - Social neuroscience is a new, interdisciplinary field devoted to understanding how biological systems implement social processes and behavior. Social neuroscience capitalizes on biological concepts and methods to inform and refine theories of social behavior, and it uses social and behavioral constructs and data to inform and refine theories of neural organization and function. We focus here on the progress and potential of social neuroscience in the area of mental health. Research in social neuroscience has grown dramatically in recent years. Among the most active areas of research we found are brain-imaging studies in normal children and adults; animal models of social behavior; studies of stroke patients; imaging studies of psychiatric patients; and research on social determinants of peripheral neural, neuroendocrine, and immunological processes. We also found that these areas of research are proceeding along largely independent trajectories. Our goals in this article are to review the development of this field, examine some currently promising approaches, identify obstacles and opportunities for future advances and integration, and consider how this research can inform work on the diagnosis and treatment of mental disorders. PMID- 26151957 TI - A Dynamical Systems Approach to the Development and Expression of Female Same-Sex Sexuality. AB - Researchers have documented substantial variability in the development and expression of same-sex sexuality, especially among women, posing challenges to traditional linear developmental models. In this article, I argue for a new approach to conceptualizing the development and expression of female same-sex sexuality over the life course, based in dynamical systems theory. Dynamical systems models seek to explain how complex patterns emerge, stabilize, change, and restabilize over time. Although originally developed by mathematicians and physicists to model complex physical phenomena in the natural world, they have increasingly been applied to social-behavioral phenomena, ranging from motor development to cognition to language. I demonstrate the utility of this approach for modeling change over time in female same-sex sexuality, reviewing extant published research and also introducing data collected from an ongoing, 10-year longitudinal study of young nonheterosexual women. I provide evidence that female same-sex sexuality demonstrates the emblematic features of a dynamical system: nonlinear change over time, spontaneous emergence of novel forms, and periodic reorganizations and phase transitions within the overall system. I highlight the specific contribution of a dynamical systems perspective for understanding such phenomena and suggest directions for future study. PMID- 26151958 TI - "Leaky" Rationality: How Research on Behavioral Decision Making Challenges Normative Standards of Rationality. AB - For more than 30 years, decision-making research has documented that people often violate various principles of rationality, some of which are so fundamental that theorists of rationality rarely bother to state them. We take these characteristics of decision making as a given but argue that it is problematic to conclude that they typically represent departures from rationality. The very psychological processes that lead to "irrational" decisions (e.g., framing, mental accounting) continue to exert their influence when one experiences the results of the decisions. That is, psychological processes that affect decisions may be said also to "leak" into one's experience. The implication is that formal principles of rationality do not provide a good enough normative standard against which to assess decision making. Instead, what is needed is a substantive theory of rationality-one that takes subjective experience seriously, considers both direct and indirect consequences of particular decisions, considers how particular decisions fit into life as a whole, and considers the effects of decisions on others. Formal principles may play a role as approximations of the substantive theory that can be used by theorists and decision makers in cases in which the formal principles can capture most of the relevant considerations and leakage into experience is negligible. PMID- 26151959 TI - What Do Implicit Measures Tell Us?: Scrutinizing the Validity of Three Common Assumptions. AB - Experimental paradigms designed to assess "implicit" representations are currently very popular in many areas of psychology. The present article addresses the validity of three widespread assumptions in research using these paradigms: that (a) implicit measures reflect unconscious or introspectively inaccessible representations; (b) the major difference between implicit measures and self reports is that implicit measures are resistant or less susceptible to social desirability; and (c) implicit measures reflect highly stable, older representations that have their roots in long-term socialization experiences. Drawing on a review of the available evidence, we conclude that the validity of all three assumptions is equivocal and that theoretical interpretations should be adjusted accordingly. We discuss an alternative conceptualization that distinguishes between activation and validation processes. PMID- 26151960 TI - Considerations Relating to the Study of Group Differences in Intelligence. AB - There are signs that the debate over racial and gender differences in intelligence is about to begin again. In this article we will be concerned primarily with racial differences but will make remarks about gender differences where applicable. Previously there have been bitter arguments over whether or not races exist, over whether it is either important or proper to study racial and gender differences in intelligence, and over the conclusions that have been drawn about environmental and genetic causes as determinants of these differences. We argue that races do, indeed, exist and that studying differences in cognitive competence between groups is a reasonable thing to do. We also point out that past research on both racial and gender differences in intelligence has been marked by methodological errors and overgeneralizations by researchers on all sides of the issue. We propose ten principles of design, analysis, and reporting that ought to be considered carefully when doing or evaluating research in this area. PMID- 26151961 TI - Barriers to Understanding Racial Differences in Intelligence: Commentary on Hunt and Carlson (2007). AB - Hunt and Carlson (2007), (this issue) present sensible guidelines for the conduct of research on group differences in intelligence. In this response, I want to indicate why I believe that their call for more research is not likely, in the near term, to lead to a clarification of the reasons for racial differences in performance on tests of intelligence. There are three barriers to progress in this field that I will consider. First, there are gaps in knowledge that render the interpretation of research problematic (see Brody, 2003, for a discussion of the indeterminate nature of research alleged to support a genetic basis for racial differences in intelligence). Second, structural inequalities in social arrangements may lead to problematic outcomes for many studies of racial differences in intelligence. Third, conceptual confusions derived from the consideration of race as a category and not as a continuum render group comparisons suspect. PMID- 26151962 TI - Applying Double Standards to "Divisive" Ideas: Commentary on Hunt and Carlson (2007). PMID- 26151963 TI - The Difficulty of Escaping Preconceptions in Writing an Article About the Difficulty of Escaping Preconceptions: Commentary on Hunt and Carlson (2007). PMID- 26151964 TI - Reply to Commentators. PMID- 26151965 TI - The Ability of Posters to Enhance the Comfort Level with Breastfeeding in a Public Venue in Rural Newfoundland and Labrador. AB - BACKGROUND: The acceptance and support of breastfeeding in public venues can influence breastfeeding practices and, ultimately, the health of the population. OBJECTIVE: The primary aim of this study was to investigate whether posters targeted at the general public could improve acceptability of breastfeeding in public places. METHODS: A convenience sample of 255 participants was surveyed at shopping centers in 2 rural communities of Newfoundland and Labrador. Experimentally, questions were posed to 117 participants pre- and post-exposure to 2 specific posters designed to promote public acceptance of breastfeeding in public. RESULTS: Initially, we surveyed that only 51.9% of participants indicated that they were comfortable with a woman breastfeeding anywhere in public. However, context played a role, whereby a doctor's office (84.5%) or park (81.4%) were the most acceptable public places for breastfeeding, but least acceptable was a business office environment (66.7%). Of participants, 35.4% indicated previously viewing specific posters. We used a visual analog scale to test poster viewing on the acceptability of public breastfeeding in the context of a doctor's office and a restaurant. Results of pre- versus post-viewing of the promotional posters indicated significant improvements in both scenarios: in a doctor's office (P = .035) and in a restaurant (P = .021). CONCLUSION: Nearly 50% of the surveyed population indicated discomfort with a mother breastfeeding in public. Both cross-sectional and interventional evidence showed that posters significantly improved the reported level of comfort toward seeing breastfeeding in public. PMID- 26151966 TI - Psychometric Properties of the Iowa Infant Feeding Attitude Scale among a Multiethnic Population during Pregnancy. AB - BACKGROUND: The Iowa Infant Feeding Attitude Scale (IIFAS) was developed to measure maternal attitudes toward infant feeding, but a number of validated studies on the IIFAS found that it was subject to methodological limitations. OBJECTIVE: The purpose of this study was to evaluate the psychometric properties of the IIFAS among a multiethnic population in Singapore. METHODS: A cross sectional research design was used on a sample of 417 antenatal women. The internal consistency and stability of the IIFAS were evaluated using Cronbach's alpha and test-retest reliability. Known-group comparisons discriminated certain group differences in a predictable way. A series of exploratory factor analyses (EFAs) was conducted to test the factor structure of the IIFAS using the maximum likelihood and principal axis factoring. The number of factors was selected according to theoretical and statistical considerations. A confirmatory factor analysis (CFA) was further performed to validate the factor structure constructed in the prior EFA. RESULTS: The IIFAS had a Cronbach's alpha and Pearson correlation of 0.79 and 0.85, respectively. The known-group comparisons among certain groups were supported. The EFA results showed that the 3-factor structure produced the most interpretable and theoretical sense. A second-order CFA was conducted to confirm the construct dimensionality of the 15-item IIFAS, with satisfactory fit indices found. CONCLUSION: The 15-item IIFAS is a psychometrically sound measurement tool that health care professionals can use to understand the diverse infant feeding attitudes and knowledge among different ethnic groups in order to provide breastfeeding interventions that are culturally sensitive. PMID- 26151967 TI - Emotion Refinement: A Theory Inspired by Chinese Poetics. AB - William James made a distinction between coarse and noncoarse emotions. In the present article, we explore the nature of such noncoarse emotions, which we designate as emotions with refinement. We take our cue from the treatment of refined emotions in Chinese poetics and philosophy. The theory and description of savoring(in Chinese, p'in-wei) points to several features of emotion experiences and behavior that are usually absent in direct emotional responses to emotional events, such as self-reflexivity and higher level second-order awareness, detachment, and restraint. Emotions with those features can be found outside savoring and aesthetic contexts, for instance while dealing with actual life events. It appears both feasible and illuminating to analyze such emotion experiences and behavior in terms of current emotion theory, notably by means of the constructs of appraisal and action readiness. Emotions with refinement thus fit general emotion theory while also possessing distinctive character within the motion domain. Our analysis has implications for the structure of emotion experience and the study of consciousness. PMID- 26151968 TI - Ideal Affect: Cultural Causes and Behavioral Consequences. AB - Most research focuses on actual affect, or the affective states that people actually feel. In this article, I demonstrate the importance and utility of studying ideal affect, or the affective states that people ideally want to feel. First, I define ideal affect and describe the cultural causes and behavioral consequences of ideal affect. To illustrate these points, I compare American and East Asian cultures, which differ in their valuation of high-arousal positive affective states (e.g., excitement, enthusiasm) and low-arousal positive affective states (e.g., calm, peace-fulness). I then introduce affect valuation theory, which integrates ideal affect with current models of affect and emotion and, in doing so, provides a new framework for understanding how cultural and temperamental factors may shape affect and behavior. PMID- 26151969 TI - Basic Emotions, Natural Kinds, Emotion Schemas, and a New Paradigm. AB - Research on emotion flourishes in many disciplines and specialties, yet experts cannot agree on its definition. Theorists and researchers use the term emotion in ways that imply different processes and meanings. Debate continues about the nature of emotions, their functions, their relations to broad affective dimensions, the processes that activate them, and their role in our daily activities and pursuits. I will address these issues here, specifically in terms of basic emotions as natural kinds, the nature of emotion schemas, the development of emotion-cognition relations that lead to emotion schemas, and discrete emotions in relation to affective dimensions. Finally, I propose a new paradigm that assumes continual emotion as a factor in organizing consciousness and as an influence on mind and behavior. The evidence reviewed suggests that a theory that builds on concepts of both basic emotions and emotion schemas provides a viable research tool and is compatible with more holistic or dimensional approaches. PMID- 26151970 TI - Neurologizing the Psychology of Affects: How Appraisal-Based Constructivism and Basic Emotion Theory Can Coexist. AB - Abundant neurobehavioral data, not discussed by Lisa Feldman Barrett (2006), support the existence of a variety of core emotional operating systems in ancient subneocortical regions of the brain (Panksepp, 1998a, 2005a). Such brain systems are the primary-process ancestral birthrights of all mammals. There may be as many genetically and neurochemically coded subcortical affect systems in emotionally rich medial regions of the brain as there are "natural" emotional action systems in the brain. When emotional primes are aroused directly, as with local electrical or chemical stimulation, the affective changes sustain conditioned place preferences and place aversions, which are the premier secondary-process indices of affective states in animals. Humans are not immune to such brain manipulations; they typically exhibit strong emotional feelings. Human emotion researchers should not ignore these systems and simply look at the complex and highly variable culturally molded manifestations of emotions in humans if they wish to determine what kinds of "natural" emotional processes exist within all mammalian brain. Basic emotion science has generated workable epistemological strategies for under-standing the primal sources of human emotional feelings by detailed study of emotional circuits in our fellow animals. PMID- 26151972 TI - The Optimum Level of Well-Being: Can People Be Too Happy? AB - Psychologists, self-help gurus, and parents all work to make their clients, friends, and children happier. Recent research indicates that happiness is functional and generally leads to success. However, most people are already above neutral in happiness, which raises the question of whether higher levels of happiness facilitate more effective functioning than do lower levels. Our analyses of large survey data and longitudinal data show that people who experience the highest levels of happiness are the most successful in terms of close relationships and volunteer work, but that those who experience slightly lower levels of happiness are the most successful in terms of income, education, and political participation. Once people are moderately happy, the most effective level of happiness appears to depend on the specific outcomes used to define success, as well as the resources that are available. PMID- 26151973 TI - A Trio of Concerns. AB - This essay assesses the two most significant changes in psychology over the past century: the attempt to localize psychological phenomena in restricted brain sites and the search for genetic contributions to behavior and psychopathology. Although there are advantages to these new developments, they are accompanied by some questionable assumptions. Because the investigators in these domains often relate variation in their biological measures to variation in personality traits evaluated with questionnaires, an analysis of the unique properties of the verbalreport questionnaires is presented. It is suggested that future research on human personality should try to combine semantic reports with behaviors and biological data in order to arrive at more fruitful constructs. PMID- 26151971 TI - The Power of Personality: The Comparative Validity of Personality Traits, Socioeconomic Status, and Cognitive Ability for Predicting Important Life Outcomes. AB - The ability of personality traits to predict important life outcomes has traditionally been questioned because of the putative small effects of personality. In this article, we compare the predictive validity of personality traits with that of socioeconomic status (SES) and cognitive ability to test the relative contribution of personality traits to predictions of three critical outcomes: mortality, divorce, and occupational attainment. Only evidence from prospective longitudinal studies was considered. In addition, an attempt was made to limit the review to studies that controlled for important background factors. Results showed that the magnitude of the effects of personality traits on mortality, divorce, and occupational attainment was indistinguishable from the effects of SES and cognitive ability on these outcomes. These results demonstrate the influence of personality traits on important life outcomes, highlight the need to more routinely incorporate measures of personality into quality of life surveys, and encourage further research about the developmental origins of personality traits and the processes by which these traits influence diverse life outcomes. PMID- 26151974 TI - Proceeding From Observed Correlation to Causal Inference: The Use of Natural Experiments. AB - This article notes five reasons why a correlation between a risk (or protective) factor and some specified outcome might not reflect environmental causation. In keeping with numerous other writers, it is noted that a causal effect is usually composed of a constellation of components acting in concert. The study of causation, therefore, will necessarily be informative on only one or more subsets of such components. There is no such thing as a single basic necessary and sufficient cause. Attention is drawn to the need (albeit unobservable) to consider the counterfactual (i.e., what would have happened if the individual had not had the supposed risk experience). Fifteen possible types of natural experiments that may be used to test causal inferences with respect to naturally occurring prior causes (rather than planned interventions) are described. These comprise five types of genetically sensitive designs intended to control for possible genetic mediation (as well as dealing with other issues), six uses of twin or adoptee strategies to deal with other issues such as selection bias or the contrasts between different environmental risks, two designs to deal with selection bias, regression discontinuity designs to take into account unmeasured confounders, and the study of contextual effects. It is concluded that, taken in conjunction, natural experiments can be very helpful in both strengthening and weakening causal inferences. PMID- 26151975 TI - Psychology as the Science of Self-Reports and Finger Movements: Whatever Happened to Actual Behavior? AB - Psychology calls itself the science of behavior, and the American Psychological Association's current "Decade of Behavior" was intended to increase awareness and appreciation of this aspect of the science. Yet some psychological subdisciplines have never directly studied behavior, and studies on behavior are dwindling rapidly in other subdisciplines. We discuss the eclipse of behavior in personality and social psychology, in which direct observation of behavior has been increasingly supplanted by introspective self-reports, hypothetical scenarios, and questionnaire ratings. We advocate a renewed commitment to including direct observation of behavior whenever possible and in at least a healthy minority of research projects. PMID- 26151976 TI - Emotion Feelings Stem from Evolution and Neurobiological Development, Not From Conceptual Acts: Corrections for Barrett et al. (2007). AB - Contrary to the arguments of Barrett et al. (2007) in critiquing Izard (2007), emotion feelings (the key component of human emotions) stem from evolution and neurobiological development, not from conceptual acts. Barrett et al. made several other erroneous and seriously misleading criticisms of Izard (2007), and they had little to say about the final two thirds of that article-an explication of emotion schemas and a new paradigm. PMID- 26151977 TI - Measuring the Immeasurable: Or "Could Abraham Lincoln Take the Implicit Association Test?". AB - With the Association for Psychological Science's new ethical standards requiring that all research studies include an Implicit Association Test (IAT), forecasters predict that the population of new participants available to take IATs will expire by the year 2023. Shrill, doomsday proposals from IAT experts involve rationing the precious pool of remaining IAT novices or other naive strategies. These solutions demonstrate rigid, scientific thinking, with a distinct lack of the creative flair that makes psychology stand apart from the real sciences. Building on our prior experience of adapting the IAT for measuring infant cognition and rooting out aliens among us, we demonstrate that new pools of participant resourcesmdash;the unborn and passed on-are available, if we take the time to develop the methods to exploit them. Two studies illustrate some of the methodological challenges and opportunities that must be met in order to make better use of the new populations to keep the IAT juggernaut on its path of global (and interstellar) domination. PMID- 26151978 TI - Volume 2, 2007. PMID- 26151979 TI - Psychological Science Can Improve Diagnostic Decisions. PMID- 26151980 TI - The Scientific Status of Projective Techniques. AB - Although projective techniques continue to be widely used in clinical and forensic settings, their scientific status remains highly controversial. In this monograph, we review the current state of the literature concerning the psychometric properties (norms, reliability, validity, incremental validity, treatment utility) of three major projective instruments: Rorschach Inkblot Test, Thematic Apperception Test (TAT), and human figure drawings. We conclude that there is empirical support for the validity of a small number of indexes derived from the Rorschach and TAT. However, the substantial majority of Rorschach and TAT indexes are not empirically supported. The validity evidence for human figure drawings is even more limited. With a few exceptions, projective indexes have not consistently demonstrated incremental validity above and beyond other psychometric data. In addition, we summarize the results of a new meta-analysis intended to examine the capacity of these three instruments to detect child sexual abuse. Although some projective instruments were better than chance at detecting child sexual abuse, there were virtually no replicated findings across independent investigative teams. This meta-analysis also provides the first clear evidence of substantial file drawer effects in the projectives literature, as the effect sizes from published studies markedly exceeded those from unpublished studies. We conclude with recommendations regarding the (a) construction of projective techniques with adequate validity, (b) forensic and clinical use of projective techniques, and (c) education and training of future psychologists regarding projective techniques. PMID- 26151981 TI - Introduction to inactivated polio vaccine and switch from trivalent to bivalent oral poliovirus vaccine worldwide, 2013-2016. PMID- 26151982 TI - Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis (data received in WHO headquarters as of 16 June 2015). PMID- 26151983 TI - Sexual Stimulation and Sexual Selection. PMID- 26151984 TI - [In Process Citation]. PMID- 26151985 TI - Study of natural causes of death in medicolegal autopsies seen in University of Benin Teaching Hospital. AB - AIMS AND OBJECTIVES: To provide a comprehensive report on the various causes of natural death in our centre and consider its implication for prevention. MATERIALS AND METHODS: A descriptive cross sectional study of post mortem reports, autopsy registers and duplicate copies of death certificates of all cases of SND on which autopsy was performed on in UBTH, Benin City, between 1990 and 2009. RESULTS: Of the 4481 medicolegal deaths autopsied during the period, 2734 (61.0%) cases were SND, involving 1614 males and 1120 females with a M:F ratio of 1:4:1. The modal age group was 25-44 years which accounted for 30.2% of the cases. Cardiovascular system diseases occurred most and accounted for 30.2% of all cases, with complications of hypertension accounting for 79.5% of all cardiovascular system diseases. Other causes of SND include; gastrointestinal/hepatic diseases, 15.1%; respiratory system diseases, 13.8%; genitourinary system diseases, 10.1%; immune/infectious diseases, 9.9% and endocrine/metabolic diseases, 7.7%. Less common causes are central nervous system diseases, haematolymphoid system diseases, breast diseases retroperitoneal diseases and musculoskeletal system disease each accounting for 6.6%, 5.4%, 0.7%, 0.4%, and 0.1% respectively. CONCLUSION: Cardiovascular system diseases, with complications of hypertension are the leading cause of SND in our environment. Public enlightenment on the need for routine medical health checks will help to reduce the incidence of SND. PMID- 26151986 TI - Preface: Heart valves. PMID- 26151987 TI - Studies on the mechanism of action of picrotoxinin and other convulsants at the crustacean muscle GABA receptor. AB - The actions of picrotoxinin, bicuculline and penicillin-G were investigated on the GABA-receptor system of lobster muscle by using intracellular recording. The highly potent antagonist, picrotoxinin, produced a lateral shift and depression in the maximum of the GABA dose--conductance curve (designated as mixed antagonism); bicuculline, a weak antagonist, caused only a depression in the maximum with little or no lateral shift, whereas penicillin-G, an even weaker antagonist, produced a greater depression at the top of the dose--response curve. The possible sites of antagonist action were examined, with a critical re evaluation of a drug-receptor model previously proposed to account for the antagonistic behaviour of picrotoxinin (the mixed antagonistic model); this model was extended to include the actions of bicuculline and penicillin-G. Antagonism was examined (i) towards different GABA receptor agonists; (ii) in various external anion media; (iii) at varying external pH; and (iv) when two different antagonists were combined. The GABA agonists were differentially antagonized by picrotoxinin and bicuculline, but external pH and substituent anions caused only minor perturbations to the inhibition. Combination experiments suggested at least three sites for GABA antagonists binding on crustacean muscle: (i) the GABA recognition site or sites; (ii) the ionic selectivity site in the ionophore; and (iii) a highly lipophilic site which may be part of the GABA receptor or ionophore. The mixed antagonism model accounted for the pH and external anion data but required modification to a cyclic scheme to explain the antagonism of a partial agonist. A model based on two-state receptor theory could only account for the antagonism of GABA if picrotoxinin was assumed not only to perturb L (the R rightleftharpoons T conformation constant) but also to affect the agonist binding affinity. It is suggested that picrotoxinin and bicuculline may antagonize GABA responses by stabilizing the closed form of the activated channel, whereas penicillin-G may block the channel in the open state. PMID- 26151988 TI - Medicare Payment Reform: Aligning Incentives for Better Care. AB - The Affordable Care Act (ACA) has provided the Medicare program with an array of tools to improve the quality of care that beneficiaries receive and to increase the efficiency with which that care is provided. Notably, the ACA has created the Center for Medicare and Medicaid Innovation, which is developing and testing promising new models to improve the quality of care provided to Medicare beneficiaries while reducing spending. These new models are part of an effort by the U.S. Department of Health and Human Services to increase the proportion of traditional Medicare payments tied to quality or value to 85 percent by 2016 and 90 percent by 2018. This issue brief, one in a series on Medicare's past, present, and future, explores the evolution of Medicare payment policy, the potential of value-based payment to improve care for beneficiaries and achieve savings, and strategies for accelerating its adoption. PMID- 26151989 TI - Physical and Kinetic Properties of Carbamyl Phosphate Synthetase from Frog Liver. PMID- 26151990 TI - ABFM to Simplify Maintenance of Certification (MOC) for Family Physicians and Make It More Meaningful: A Family Medicine Registry. PMID- 26151991 TI - Sympathomimetic amines are a safe, highly effective therapy for several female chronic disorders that do not respond well to conventional therapy. AB - PURPOSE: To evaluate the efficacy of sympathomimetic amine therapy for women with chronic disorders including, but not limited to, pelvic pain. MATERIALS AND METHODS: Dextroamphetamine sulfate 15-mg extended release capsules were given to women with a variety of treatment refractory conditions including, but not limited to, pelvic pain. The dosage could be increased to 60 mg depending on tolerance to the medication and degree of improvement of the condition. RESULTS: A very high percentage showed marked amelioration of their symptoms despite previous failure with medical or surgical therapy. CONCLUSIONS: The human species, especially women, seem to be more prone to certain specific tissue permeability defects and diminished sympathetic tone, which compounds the problem, since the sympathetic nervous system controls permeability. Thus, besides pelvic pain and interstitial cystitis, dextroamphetamine sulfate, which seems to restore sympathetic tone possibly by increasing dopamine secretion to the nerve fiber, provides gratifying relief to a variety of chronic disorders. These other disorders include: severe headaches, inflammatory bowel disease, gastrointestinal motility disorders, fibromyalgia, and other musculoskeletal pain, chronic fatigue syndrome, and urticaria. PMID- 26151992 TI - Detection of a microgonadotropinoma by magnetic resonance imaging performed because of excellent response to controlled ovarian hyperstimulation despite elevated day 3 FSH. AB - PURPOSE: To determine if a better response than anticipated to controlled ovarian stimulation in a woman assumed to have diminished oocyte reserve based on an increased day 3 serum follicle stimulating hormone (FSH) level, could be related to a gonadotropinoma. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) with and without gadolinium contrast was used in a woman who made 21 mature oocytes despite a history of day 3 serum FSH as high as 20 mIU/mL. RESULTS: A pituitary microgonadotropinoma was detected. CONCLUSIONS: The presence of a better response than anticipated to controlled ovarian hyperstimulation (COH) with exogenous gonadotropins despite an increase in day 3 serum FSH should prompt a search for a possible gonadotropinoma. PMID- 26151993 TI - The effect of a rise or fall of serum estradiol the day before oocyte retrieval in women aged 40-42 with diminished egg reserve. AB - PURPOSE: To determine the effect of a drop in serum estradiol the day after injection of human chorionic gonadotropin (hCG) in in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-42 with diminished oocyte reserve. MATERIALS AND METHODS: Retrospective study with further requirement that the female partner had a day 3 serum follicle stimulating hormone (FSH) of >= 12 miU/mL and >= five antral follicles. RESULTS: A drop in serum estradiol the day after hCG injection is not associated with a lower chance of pregnancy compared to those women whose serum estradiol increases. However, their chances of releasing the oocyte before retrieval is significantly higher. CONCLUSIONS: A drop in serum estradiol in women of advanced reproductive age with diminished oocyte reserve should not signal the need to cancel the retrieval. PMID- 26151994 TI - Depressive symptoms and hormonal profile in climacteric women. AB - OBJECTIVES: The aims of the study were: evaluation of depressive symptoms in climacteric women, comparison of depressive symptoms between peri- and post menopausal women, and assessment of a possible relationship between the presence of depressive symptoms and the hormonal profile of the studied women. MATERIALS AND METHODS: The study included 45 peri-menopausal and 95 post-menopausal women admitted to the Department of Gynecological Endocrinology, Poznafi University of Medical Sciences, because of climacteric symptoms. The following parameters were evaluated in all studied women: intensity of climacteric symptoms (Kupperman Index), intensity of depressive symptoms (Hamilton depression scale), serum concentrations of hypothalamic-pituitary-gonadal axis hormones (FSH, LH, 17beta estradiol), prolactin (PRL) and androgens [total testosterone, dehydroepiandrosterone sulfate (DHEAS)]. FSH, LH, 17beta-estradiol, PRL, and total testosterone were evaluated by the immunoenzymatic methods and DHEAS was measured by the radioimmunological method. RESULTS: Psychic and somatic manifestations of anxiety and fear, shallow sleep, and general somatic symptoms were the most frequent depressive symptoms in both studied groups. Both investigated groups differed in relation to the incidence and intensity of symptoms from the genital system (observed more often in post-menopausal women) and hypochondria (noted more frequently in peri-menopausal women). Numerous relationships between the incidence and intensity of certain symptoms and serum concentrations of the investigated hormones were found in both groups. The correlations were different in peri- and post-menopausal subjects. PMID- 26151995 TI - Scar endometriosis is a gynecological complication that general surgeons have to deal with. AB - BACKGROUND: Scar endometriosis is the presence of functional endometrium tissue in surgical incisions. It is a complication that develops after obstetrical or gynecological surgical procedures. As it presents with a mass adjacent to surgical incisions, general surgeons usually deal with it. The authors' aim was to review and discuss the differential diagnosis, treatment methods, recurrence rate, and follow up of scar endometriosis. MATERIALS AND METHODS: Data of patients diagnosed with incisional scar endometriosis between 2005 and 2012 were recorded retrospectively. Their initial symptoms, previous surgery histories, onset of symptoms after surgery, duration of symptoms, diagnostic modalities, treatment methods, pathological evaluations, and rate of recurrences were documented and analyzed. RESULTS: Seventeen patients were diagnosed to have scar endometriosis. Former surgical histories were one hysterectomy, one vaginal birth with episiotomy, and 15 cesarean sections. Sixteen of the scar endometrioses were demonstrated on pfannenstiel incision and one on episiotomy scar. Only one recurrence was seen during follow up. CONCLUSION: Scar endometriosis should be taken into account in the surgical practice of incisional site masses of the abdominal wall. They should be excised totally for a proper treatment. Patients must be warned about malignancy risk. PMID- 26151996 TI - Effects of estrogen intervention on the biomechanical characteristics of serum SOD, MDA, and middle cerebral artery in aged female rats. AB - OBJECTIVE: This study aims to study the biological and biomechanical characteristics of the middle cerebral artery (MCA) in aged and estrogen intervened aged rats, thereby providing biomechanical basis for clinics. MATERIALS AND METHODS: Thirty 18-month-old Sprague Dawley (SD) rats, 30 18-month old estrogen-intervened SD rats, and 30 four-month-old SD rats were studied. The estrogen-intervened rats were given estradiol benzoate on the fifth feeding day. Thirty-four days after the feeding, the serum of each rat was obtained. The radioimmunoassay was performed for the content determination of serum E2, ER, malondialdehyde (MDA), and superoxide dismutase (SOD). The tensile test was performed to evaluate the MCA of each rat. RESULTS: Through the estrogen intervention, the serum contents of E2, ER, SOD, and MDA in old rats were restored to normal levels. The maximum stress, maximum strain, and elastic limit of the MCA in the aged estrogen-intervened rat group were greater than those of the non-intervened aged rat group, with a significant difference (p < 0.05). The elastic modulus in the aged estrogen-intervened rat group was less than that of the non-intervened aged rat group, with a significant difference (p < 0.05). CONCLUSION: E2 intervention can improve the flexibility, toughness, and compliance of MCA in aged rats. PMID- 26151997 TI - Female genital mutilation/cutting: an update. AB - Female genital mutilation/cutting (FGM/C) is a cultural practice involving several types of external female genitalia cutting. FGM/C is known to occur in all parts of the world but is most prevalent in 28 countries in Africa and the Middle East and among immigrant communities in Europe, Australia, New Zealand, Canada, and the United States. Studies of FGM/C suffer from many methodological problems including inadequate analysis and an unclear reporting of results. The evidence to link FGM/C to infertility is weak. The management of epidermal clitoral inclusion cysts includes expensive investigations like comprehensive endocrinology tests and MRI resulting in unnecessary anxiety due to delay in surgical treatment. Similarly, unnecessary cesarean sections or rupture of the infibulation scar continue to occur because of the inadequate use of intrapartum defibulation. A significant amount of efforts is required to improve and correct the inadequate care of FGM/C women and girls. PMID- 26151998 TI - Effect of skin contact between mother and child in pain relief of full-term newborns during heel blood collection. AB - OBJECTIVES: The aim was to investigate the effect of skin contact between mother and child in pain relief of full-term newborns during heel blood collection. MATERIALS AND METHODS: The authors randomly divided 40 full-term newborns into two groups. In the experimental group, the newborn received kangaroo care from the mother before, during, and after the 20-minute heel blood collection. In the control group, the heel blood collection was performed under conventional conditions. The authors compared the two groups' heart rate, oxygen saturation, facial expressions of pain, and duration of crying. RESULTS: The two groups had no statistically significant difference in terms of gender, birth weight, mode of delivery, and gestational age (p > 0.05). In the seven time periods during the puncture after ten seconds from the beginning and ten seconds after the end, the neonatal heart rates of the two groups changed and statistically significant differences were observed in the duration of heel blood collection, interaction and group factors, as well as in oxygen saturation (p < 0.01). CONCLUSIONS: During heel blood collection, skin contact between the mother and child can relieve pain, reduce changes in heart rate, improve neonatal heel blood oxygen saturation, and enhance the emotional communication between the mother and child. PMID- 26151999 TI - Do combined psychological stress examinations predict pregnancy outcome in an assisted reproductive technology program? AB - PURPOSE OF INVESTIGATION: To investigate prospectively if the pregnancy outcome in infertile women undergoing assisted reproductive technology (ART) is predictable by a combination of psychological stress examinations on the day of embryo/blastocyst transfer. MATERIALS AND METHODS: From April 2012 to May 2012, 114 women aged 42 years old or less underwent transfer of morphologically-good embryo/blastocyst(s) in the present in vitro fertilization (IVF) center. Immediately before the transfer, salivary secretion was obtained and frozen. alpha-amylase and cortisol concentrations were quantified using biochemical assays. In addition, patients were asked to answer General Health Questionnaire 28 (GHQ28) and Zung's Self Rating Depression Scale (SDS) following transfer. The results were compared between the pregnant group and non-pregnant group. RESULTS: There were no significant differences in the age of the infertile couples between the pregnant group and non-pregnant group as well as body mass index of the infertile women. The GHQ28 and SDS scores were similar between the two groups, as were the salivary alpha-amylase and cortisol concentrations. CONCLUSION: This prospective study failed to demonstrate the predictivity of the pregnancy outcome by psychological stress examinations in infertile women in an ART program, even though these tests were used in combination. PMID- 26152000 TI - Time-limited hydrotubation combined with clomiphene citrate treatment for unexplained infertility. AB - PURPOSE: To evaluate time-limited hydrotubation combined with clomiphene citrate as treatment for unexplained infertility. MATERIALS AND METHODS: In this unblinded, randomized controlled trial of patients who had unexplained infertility, 40 patients were treated with time-limited hydrotubation (saline, 20 ml; flushed within 20 to 30 seconds) and clomphene citrate (total, 70 cycles) and 40 patients were treated with clomiphene citrate alone (total, 74 cycles). All women underwent an ovulation induction protocol with clomiphene citrate (100 mg/d orally for five days, from day 3 to day 7 of the cycle). Hydrotubation was performed after detection of the dominant follicle. RESULTS: There were 15 pregnancies in the 80 patients (19%) (total, 144 stimulated cycles; 10% pregnancies per cycle). The frequency of clinical pregnancy per cycle was significantly greater in patients who were treated with hydrotubation and clomiphene citrate (nine pregnancies per cycle [13%]) than those treated with clomiphene citrate alone (two pregnancies per cycle [3%]; odds ratio, 5.3; 95% confidence interval, 1.1 to 25.5; p <= 0.05). The frequency of pregnancy per patient (total, clinical, or chemical) was similar for the two treatment groups. The frequency of live birth or abortion per cycle or patient was similar between the two treatment groups. CONCLUSION: Time-limited hydrotubation and clomiphene citrate may increase the frequency of clinical pregnancy per cycle in women who have unexplained infertility. PMID- 26152001 TI - Exploring the significance of sex hormone-binding globulin examination in the treament of women with polycystic ovarian syndrome (PCOS). AB - OBJECTIVES: To explore whether sex hormone-binding globulin (SHBG) and free androgen index (FAI) can be seen as therapeutic effect indexes of women with polycystic ovarian syndrome (PCOS). MATERIALS AND METHODS: The body mass index (BMI), basal sexual hormones, SHBG, fasting blood glucose (FBG), and fasting insulin (FINS) were collected from 579 women with PCOS, were divided into two groups according to BMI: obese group (n = 145) and non-obese group (n = 434), according to homeostasis model assessment of insulin status (HOMA-IR). Patients were then divided into four groups: A: non-obese without insulin resistance (n = 174), B: non-obese with insulin resistance (n = 260), C: obese without insulin resistance (n = 34), D: obese with insulin resistance (n = 111). A and B groups received Diane-35 alone, C and D groups received Diane-35 plus metformin for three months. Then clomiphene citrate and HMAG were used to induce ovulation then compared ovulation rate and pregnancy outcome. RESULTS: FAI decreased significantly and SHBG increased significantly in all groups. In A group FINS and HOMA-IR increased significantly (p < 0.05), but in B and D groups FINS and HOMA IR decreased significantly (p < 0.05). After treatment the ovulation rate in non obese group was higher than obese group (p < 0.01). Compared with non-ovulation patients, SHBG increased significantly and FAI decreased significantly in the patient with ovulation. Regarding the pregnancy outcome, FAI decreased significantly in delivery patients than spontaneous abortion patients. Furthermore, SHBG increased significantly. CONCLUSION: It was important to check SHBG and FAI during the treatment of PCOS patient. They could be used to assess whether the treatment was effective and as a guidance of clinical medication. PMID- 26152002 TI - Possible role of perineal ultrasound in the diagnosis of cystocele. AB - OBJECTIVE: Perineal ultrasound has not yet been adequately evaluated in relation to the diagnosis of anatomical descensus of pelvic organs. Therefore, the aim of the present study was to assess whether it is possible to carry out a topographical comparison between bladders in normal seat and prolapsed ones and to quantify the extent of descensus. MATERIALS AND METHODS: The authors selected 140 women, divided into three groups (two control groups and one case group). All patients underwent urogynaecological examination, according to the Pelvic Organ Prolapse Quantification (POP-Q), and perineal ultrasound to evaluate pubo-bladder distance. RESULTS: Considering the data recorded in the two control groups, the authors established the physiological pubo-bladder distance between 27-33 mm at rest and 25-30 mm under stress. In the group with cystocele, the pubo-bladder distance was significantly lower: 20 mm at rest and three mm under stress (mean value). The authors also performed a classification of ultrasound cystocele in four stages, in accordance with clinical staging. CONCLUSIONS: In conclusion, the present data show the excellent potential role of perineal ultrasound in the diagnosis of cystocele, but it is necessary to perform randomized studies to standardize the method. PMID- 26152003 TI - Fetal abdominal wall defects: six years experience at a tertiary center. AB - The authors' aim was to detect the associated anomalies and their effect on the management of the fetuses with omphalocele and gastroschisis. Between the period of 2007-2013, the data of fetuses with abdominal wall defects were analyzed. Chromosomal abnormalities and associated morphologic anomalies diagnosed by ultrasonography and autopsy were evaluated. Of the. 61 fetuses, ten (20.4%) omphalocele cases and nine (75%) gastroschisis cases were isolated. Chromosomal abnormalities were found in seven fetuses with omphalocele cases. All fetuses with abnormal karyotypes had multiple additional anomalies. Termination rate was 65.3% for omphalocele group versus none in the gastroschisis group. To give better counseling about the prognosis and outcome of the fetuses with abdominal wall defects, detection of additional anomalies as well as type of the defect are essential tools even if the karyotype is normal. PMID- 26152004 TI - Ultrasonographic wall thickness measurement of the upper and lower uterine segments in the prediction of the progress of preterm labour. AB - OBJECTIVE: To assess the role of ultrasonographic measurement of the upper and lower uterine segments wall thickness in predicting the progress of preterm labour in patients presenting with preterm labour pains. STUDY DESIGN: Fifty pregnant women presenting at Obstetrics Department - Suez Canal University, Egypt with regular lower abdominal pains and diagnosed as having preterm labour were enrolled in the study. MATERIALS AND METHODS: Measurements of the upper and lower uterine segments wall thickness by transabdominal ultrasonography in-between contractions and with full bladder were taken. The upper/lower uterine wall thickness ratio was calculated and correlated to the progress of the preterm labour and to the response to tocolytics. RESULTS: The ultrasonographic upper/lower uterine wall thickness ratio was directly related to the progress of preterm delivery (PTD). The change in this ratio is correlated inversely with the response to tocolysis. Using the ROC curve, when the upper/lower uterine wall thickness ratio was <= 1.26 the sensitivity was 94.74 and the specificity was 100.00, and when the ratio was <= 1.52 the sensitivity was 100.00 and the specificity was 83.33. CONCLUSIONS: These data may serve as a baseline ultrasonographic reference values for further studies in prediction the progress of preterm labour in patients presenting with preterm labour pains. PMID- 26152005 TI - Clinical and radiographic characteristics in pulmonary endometriosis: based on five cases. AB - OBJECTIVE: This study aims to improve the diagnostic and therapeutic efficacy through analysis of clinical and radiographic characteristics in pulmonary endometriosis. MATERIALS AND METHODS: This retrospective study was conducted from January 1998 to December 2008. The clinical and radiographic characteristics of five patients diagnosed as pulmonary endometriosis were evaluated. RESULTS: Among the five female patients of reproductive age, one case presented with recurrent pneumothorax, four cases presented with recurrent hemoptysis. Episode of pneumothorax and hemoptysis had the close association with the menstrual cycle. Except for pneumothorax case, the computed tomography (CT) scans during menstruation showed patchy opacification or infiltration (n = 4). Histopathologic examination of the resected specimen conformed typical endometrial tissue in the lungs. Misdiagnosis occurred involving spontaneous pneumothorax (n = 1), pulmonary tuberculosis (TB) (n = 3), and bronchiectasis (n = 1). CONCLUSION: Pulmonary endometriosis is prone to misdiagnosis. The combination of medical history and CT scans in association with menstrual cycle was useful to make the differential diagnosis after effective diagnostic treatment of hormone therapy. PMID- 26152006 TI - Recurrence rate of ovarian endometriosis in patients treated with laparoscopic surgery and postoperative suppressive therapy. AB - INTRODUCTION: The testing represented a prospective study that was performed at the Gynaecology and Obstetrics Clinic "Narodni Front" in Belgrade during a two year period. The study encompassed female patients with ovarian endometrioma operated with laparoscopic surgery. The research objective was to determine the percentage of occurrence of relapses in patients operated for endometriosis of the ovary in relation to the stage of the disease and the type of performed operation, and which were receiving suppressive therapy with gonadotropin releasing hormone (GnRH) analogues after the surgery compared to those who were not receiving suppressive therapy after the operation. MATERIALS AND METHODS: The recurrence of endometriosis on the ovary of the test and control groups was monitored during the first year after surgery. In all patients ultrasound checks were done every month during the first six months after surgery, and then every three months for the next six months. In all patients in whom the recurrence, i.e. endometrioma on the ovary larger than three cm was revealed postoperatively by ultrasound, the laparoscopic removal of the endometrioma was performed again as well as the histopathological examination of the material. RESULTS AND CONCLUSION: There was no statistically significant difference in the distribution of recurrence of endometriosis between the groups formed according to the type of surgical technique (cystectomy or cystotomy). The recurrence of endometriosis occurred later in the group of patients in which the treatment GnRH analogues was applied after the surgical treatment. The recurrence of endometriosis in more severe stages (Stage III and IV) occurs later in the group of patients in which the treatment GnRH analogues is applied after the surgical treatment. PMID- 26152007 TI - Non-invasive prenatal diagnosis of fetal RhD by using free fetal DNA. AB - OBJECTIVE: Anti-D immunoglobulin is applied to all pregnant women having RhD incompatibility to prevent hemolytic disease of the newborn. The aim of this study is to determine fetal RhD status in the Rh incompatible pregnancies with an non-invasive technique; free fetal DNA isolation from maternal circulation. In the case of Rh incompatibility especially with a history of previous fetal anemia, it can be beneficial to know Rh status antenatally in terms of monitoring fetuses with Rh positive [RhD(+)] status consciously. MATERIALS AND METHODS: Total free DNA was isolated in 50 Rh negative [RhD(-)] pregnant women, who had RhD alloimmunisation with their husbands. The gene in isolated DNA was investigated with TagMan prob and real time PCR by using primers belonging to exon 7 of the RhD gene. RESULTS: The authors analyzed 50 RhD(-) women by using quantitative real time PCR technique. Five of them were RhD(-) and the rest of them were found to be RhD(+). After birth one of the infants who were analyzed as RhD(+) were found to be RhD(-). CONCLUSION: The detection of fetal RhD status by using a non-invasive method from maternal circulation was found to be possible. Assessing fetal RhD status non-invasively by using free fetal DNA in maternal blood will be cost-efficient, avoiding unnecessary indirect Coombs test and unnecessary Rhogam applications that is used in RH incompatible pregnancies. This study will throw a fresh light on prenatal diagnosis. PMID- 26152008 TI - Novasure impedance control system versus microwave endometrial ablation for the treatment of dysfunctional uterine bleeding: a double-blind, randomized controlled trial. AB - PURPOSE OF INVESTIGATION: To compare the efficacy and safety of two different second-generation ablation devices, Novasure impedance control system and microwave endometrial ablation (MEA), in cases of abnormal uterine bleeding (AUB). MATERIALS AND METHODS: This is a randomized controlled trial that took place in a single Gynecological Department of a University Hospital. Sixty-six women with dysfunctional uterine bleeding (DUB), unresponsive to medical treatment, were included in the trial. The ratio of women allocated to bipolar radio-frequency ablation or MEA was 1:1. Follow-up assessments were carried out at three and 12 months post-ablation. The present main outcome measure was amenorrhea rates 12-months post-treatment. RESULTS: The rate of amenorrhea at 12 months post-ablation was significantly higher in women treated by Novasure (25/33; 75.8%) as compared to those treated by MEA (8/33; 24.2%) (rate difference: +51.5%, 95% CI: +27.8 to +67.7). CONCLUSION: In women with DUB, endometrial ablation with Novasure bipolar radiofrequency impedance-controlled system is associated with increased rates of amenorrhea at 12-months post treatment as compared to the MEA method. PMID- 26152009 TI - Optimizing the modified laparoscopic Vecchietti procedure. AB - OBJECTIVE: To enhance the modified laparoscopic Vecchietti procedure. MATERIALS AND METHODS: A case series of five women with Mayer-Rokitansky-Kuster-Hauser syndrome at the Department of Obstetrics and Gynecology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia underwent the modified laparoscopic Vecchietti procedure with intraperitoneal placement of sutures. This involved perforation of the vaginal dimple by a straight thread guide with two threads attached to the olive followed by pulling the two threads intra-peritoneally and through the abdominal wall to the traction device by grasping instruments under laparoscopic control. RESULTS: Intraperitoneal placement of the sutures was easily done without complications in all five women. The operative time was 50 +/ 10 (mean +/- SD) minutes. After five postoperative days, the average vaginal length was seven to 7.5 cm. Two women were able to have vaginal intercourse without problems. After six months to one year of follow up, the vaginal length was at least ten cm and no postoperative complications occurred. CONCLUSIONS: Intraperitoneal placement of sutures makes the modified laparoscopic Vecchietti procedure easy and appealing. Furthermore, it avoids potential damage to the vital structures at the pelvic side walls. PMID- 26152010 TI - Outcomes and management strategies in pregnancies with early onset oligohydramnios. AB - OBJECTIVE: To evaluate the outcomes and management options in pregnancies with early onset oligohydramnios. MATERIALS AND METHODS: The file datas of all pregnancies diagnosed as oligohydramnios or anhydramnios before 27 gestational weeks between January 2006 and September 2013 were evaluated retrospectively. The underlying pathology and associated anomalies, karyotype analysis, the outcome of the pregnancy (either termination or labour), and gestational week at the time of diagnosis were analyzed. RESULTS: A total of 54 pregnancies were evaluated; mean gestational week at the time of the diagnosis was 19.8 +/- 4.6. Mean maternal age was 27.28 +/- 6.03. Thirty-seven pregnancies were anhydramniotic, 13 fetuses had associated anomalies, five of them had multicyctic dysplastic kidney, five had bilateral renal agenesis, one had hypoplastic right heart syndrome, one had clubfoot, and one had ventricular septal defect and cleft palate. Karyotyping was normal regarding the fetuses with structural anomalies. Nineteen patients had premature preterm rupture of membranes and 39 patients had termination of pregnancy. CONCLUSION: The prognosis of early onset oligohydramnios is poor. Main determinant is gestational week at the time of the diagnosis. PMID- 26152011 TI - Surgical management of intrauterine devices migrated towards intra-abdominal structures: 20-year experience of a tertiary center. AB - AIMS: To share surgical management experiences of intra-abdominal intrauterine devices (IUDs) in tertiary center. MATERIAL AND METHODS: A total of 27 patients were retrospectively analyzed. This retrospective study was conducted between September 1992 and April 2013 at Department of Obstetrics and Gynecology Tepecik Research and Training Hospital, Izmir, Turkey. Demographic findings, diagnostic methods, and operative notes of patients were obtained from the patient file. FINDINGS: Of the 27 IUDs, nine (33.3%) were in omentum, four (15%) were in Douglas pouch, one in left sacrouterine ligament, one in uterovesical space and one in fundus posterior, six (22%) in left adnexial region, one in abdominal wall, one was subdiaphragmatic, one in ligamentum latum, and one in jejunum. Almost all of the patients had TCu-380 A IUDs. Seventeen patients (63%) were managed by laparoscopy, whereas laparotomy was required in ten (37%). Adhesions were found in 23 of 27 (85%) patients with varying degrees. In four cases the incision was extended due to adhesions. CONCLUSION: A missing string was the first finding of an intra-abdominal IUD. Pelvic ultrasonography, X-ray, and hysteroscopy methods should be performed in order to detect the localization of IUD in case of a missing string. Surgical approach should be the first treatment option for intra-abdominal IUDs. PMID- 26152012 TI - The impact of LH, E2, and P level of HCG administration day on outcomes of in vitro fertilization in controlled ovarian hyperstimulation. AB - OBJECTIVES: The objective of this study was to evaluate the impact of luteinizing hormone (LH), estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (HCG) administration on outcomes of in vitro fertilization (IVF) in controlled ovarian hyperstimulation (COH). STUDY DESIGN: In this retrospective study, 129 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments were included; these cycles were stratified according to LH levels of >= 1.12 IU/L or < 1.12 U/L and according to E2 levels of >= 1,005.89 pmol/L or < 1,005.89 pmol/L. The main outcome measure was the clinical pregnancy rate. RESULTS: The clinical pregnancy rate was significantly higher in the group with LH >= 1.12 IU/L than in the group with LH < 1.12 U/L (43.28% vs. 30.65%, p < 0.05). The clinical pregnancy rate was also higher in the group with E2 >= 1,005.89 pmol/L than in the group with average E2 < 1,005.89 pmol/L (42.86% vs. 30.51%, p < 0.05). Among the LH, E2, and P levels on the day of HCG administration, LH level was the most important predictor of outcomes of IVF in COH. The present data showed an adverse effect of low serum LH level (LH < 1.12 IU/L) on the day of HCG administration on clinical pregnancy rate. E2 level can also predict the outcomes of IVF in COH. CONCLUSIONS: Low serum LH level (LH < 1.12 IU/L) and low serum E2 level (average E2 < 1,005.89 pmol/L) on the day of HCG administration led to low clinical pregnancy rates, while the P level on the day of HCG administration may have had little effect on clinical pregnancy. PMID- 26152013 TI - Follicular phase serum and follicular fluid glycodelin measurements in gonadotropin-releasing hormone (GnRH)-antagonist assisted reproduction cycles: A prospective cohort study. AB - PURPOSE: To establish the serum pattern for glycodelin and to investigate the possible correlations of serum and follicular fluid (FF) glycodelin with clinical pregnancy in gonadotropin-releasing hormone (GnRH)-antagonist controlled cycles. MATERIALS AND METHODS: A prospective observational study conducted with 80 infertile couples who received a GnRH-antagonist controlled cycle. Glycodelin levels were measured in FF, day 2-3, and ovarian pick-up (OPU)-day serum samples. RESULTS: There were no significant differences in serum glycodelin concentrations in either the early follicular phase or the preovulatory phase, and in FF glycodelin concentrations between clinically pregnant and non-pregnant patients. OPU-day serum glycodelin was found to be significantly higher than early follicular serum glycodelin level in all patients whether pregnancy occurred or not. CONCLUSION: Although day 2-3 and OPU-day measurements of serum glycodelin levels were not significant in predicting clinical pregnancy, the pattern of serum glycodelin seems different in GnRH-antagonist controlled cycles than natural and GnRH-agonist controlled cycles. PMID- 26152014 TI - Higher abnormal fertilization, higher cleavage rate, and higher arrested embryos rate were found in conventional IVF than in intracytoplasmic sperm injection. AB - OBJECTIVE: The aim of this study was to investigate whether performing different fertilization technologies (intracytoplasmic sperm injection [ICSI] and in vitro fertilization [IVF]) may affect the result of fertilization in the normal fertilization cycles. STUDY DESIGN: The authors performed a retrospective analysis of 164 cycles using sibling oocytes in combined IVF/ICSI with achieved a normal fertilization ( >= 25%) both conventional IVF and ICSI in this infertility centre. RESULTS: It was found that there were no differences in 2PN rate (70.25% vs 70.60%), but higher cleavage rate in ICSI than IVF insemination (98.99% vs 96.81%), higher arrested embryos rate in IVF than ICSI in 2PN group (20.00% vs 13.95%), and higher abnormal fertilization IPN (3.87% vs 1.92%) and 3PN (3.63 vs 0.854%) in IVF than ICSI. CONCLUSION: There were some differences fertilization outcomes between ICSI and IVF, which may be related to different procedures between two techniques. PMID- 26152015 TI - The confounding effect of the development of idiopathic orthostatic edema and thyrotoxcosis on weight fluctuation related to effects on free water clearance in a woman with long-standing surgically induced panhypopituitarism and diabetes insipidus. AB - PURPOSE: To evaluate the effect of idiopathic orthostatic edema and the effect of thyrotoxicosis on weight fluctuation and fluid retention in the presence of surgically induced panhypopituitarism and diabetes insipidus controlled with hormone replacement. MATERIALS AND METHODS: Dextroamphetamine sulfate was used for weight gain when no other etiologic factor was found. Methimazole was used when weight loss occurred when serum T4 and free T4 indicated thyrotoxicosis. RESULTS: Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. CONCLUSIONS: Hypopituitarism and diabetes insipidus controlled with hormone replacement do not protect against fluid retention from idiopathic edema. PMID- 26152016 TI - Late diagnosis of positive HIV serology in pregnancy incidentally discovered by the widespread appearance of Kaposi's sarcoma. AB - The authors report a case of Kaposi's sarcoma (KS) found in a pregnant woman. On discovery, the condition had spread throughout her body as is characteristic in some cases of individuals with HIV-positive serology. She was unaware of her HIV positive status. Her HIV infection had been diagnosed at the same time as KS at her last prenatal consultation. The newborn was delivered by an uncomplicated cesarean section. Appropriate treatment and multidisciplinary management after childbirth resulted in complete remission. PMID- 26152017 TI - Rupture of maternal splenic artery aneurysm and fetal demise. AB - Splenic artery aneurysm (SAA) is the third most common intra-abdominal aneurysm. This condition, which occurs predominantly in young women, is generally asymptomatic and frequently discovered during pregnancy upon rupture. Reported maternal and fetal mortality are respectively 75% and 72.5-95%. A 40-year-old woman gravida 4 para 3 was referred to the obstetrical emergencies at term for loss of consciousness, nausea, vomiting, and hypotension. At admission, the patient had developed upper abdominal pain. Fetal demise and hemoperitoneum were diagnosed. An abdominal computed tomography (CT) scan revealed SAA rupture. An emergency hemostatic splenectomy was performed followed by a cesarean section with a favorable subsequent outcome. SAA rupture should be considered in the differential diagnosis of acute abdominal pain during pregnancy. Prompt multidisciplinary management is essential for patient's survival. PMID- 26152018 TI - The use of fresh frozen plasma for reproduction in severe factor V deficiency. AB - OBJECTIVE: Severe factor V (FV) deficiency is rare. There are case reports describing pregnancy outcomes in women with FV deficiency and one case report of successful pregnancy following the use of fresh frozen plasma (FFP) in several cycles of ovulation induction and intrauterine insemination and at delivery. The authors report another case to support the use of FFP for reproduction. CASE: A 27-year-old woman with severe FV deficiency was given FFP at the time of ovulation induced with clomiphene citrate, human menopausal gonadotropin (hMG), and human chorionic gonadotropin. Intrauterine insemination (IUI) was done 35 hours later. She became pregnant with twins and delivered vaginally at 36 weeks of gestation with the prophylactic use of FFP. CONCLUSION: Fresh frozen plasma can be offered for reproduction to women with severe FV deficiency. PMID- 26152019 TI - Pregnancy associated with melanoma and fetal anomalies: a case report and review of literature. AB - The estimated incidence of melanoma complicating pregnancy has ranged from 0.1 to 2.8 per 1,000 pregnancies. Here the Authors present a case of a 40-year-old pregnant woman, who was admitted to the Clinic of Obstetrics and Gynaecology in 26 weeks of gestation, with diagnosis of melanoma and suspected with fetal anomaly, as possible bowel obstruction, and polyhydraminos. The melanoma was asported with a wide local excision under local anesthesia. Histological evaluation revealed melanoma Stage Ib (Clark IV, Breslow thickness 1.2 mm, pT2a). Lymph node sonography of neck, axilla, inguinum, abdomen, and pelvis as well as chest radiography did not demonstrate any evidence of metastatic disease. After vaginal delivery at 37 weeks of gestation, the female preterm hypotrophic newborn was transferred to the Institute for Neonatology and underwent resection of duodenojejunal atresia with tapering duodenoplasty and duodenojejunal termino terminal anastomoses due to intestinal obstruction. No evidence of the melanoma was found in the placenta. Two years later the child was healthy and the mother was disease-free. PMID- 26152020 TI - Rupture of uterine serosal hematoma: delayed complication of uterine perforation. AB - Uterine perforation, a major complication of dilatation and curettage (D&C), is typically recognized at the time of the procedure. Large defects in the uterine wall or injury to other intraabdominal organs can result in an acute abdomen requiring immediate surgical treatment. On the other hand, small perforations usually resolve on their own without any long-term consequences. Here, the authors report a case of delayed hemoperitoneum, ten days after the D&C evacuation of an early pregnancy. Initially, intramural pregnancy was the suspected etiology. However, histopathology suggested that the inciting event was the rupture of a serosal uterine hematoma, which likely resulted from an incomplete uterine perforation during D&C. The patient did well after undergoing an uneventful laparoscopy. PMID- 26152021 TI - Pregnancy in a woman with pulmonary hypertension: favorable outcome with intravenous treprostinil. AB - Pulmonary hypertension (PH) presents a high risk for maternal mortality. The intravenous administration of treprostinil has demonstrated effectiveness for the treatment of PH, though documentations of its use during pregnancy are few. The authors present a 30-year-old gravid women with symptoms of PH at 23 weeks gestation. Treatment comprised of oxygen therapy, enoxaparin, and intravenous treprostinil from gestational week 25, following a successful elective cesarean section at 33 weeks gestation with favorable outcome. This report demonstrates the effectiveness of an intensive therapeutic protocol, including intravenous treprostinil, for the treatment of PH in pregnancy. PMID- 26152022 TI - Pentalogy of Cantrell accompanied by scoliosis and pes equinovarus deformity at 12 weeks gestation. AB - Cantrell's pentalogy (CP) is a rare syndrome characterized by defects in the lower sternum with ectopia cordis, anterior diaphragm defects, midline supraumbilical abdominal wall defects, defects in the diaphragmatic pericardium, and congenital heart disease. The authors report a 12-weeks gestation with multiple fetal anomalies suggesting the diagnosis of CP (a large thoraco abdominal defect with herniating liver and bowel, heart deviated anteriorly with concomitant ventricular septal defect), and the 'S' shaped fetal spine due to increased lumbar lordosis and scoliosis with accompanying pes equinovarus deformity. Chorionic villus sampling was performed due to increased nuchal translucency (3.7 mm). The fetal karotype was found to be 47, XX,+21 (trisomy 21). In the literature, three scoliosis cases have been reported accompanying the CP along with multiple anomalies and one concomitant pes equinovarus deformity has been reported previously. PMID- 26152023 TI - Conservative surgical management of multiple myometrial abscesses; an unusual case with review of the literature. AB - Myometrial abscess, especially with multiple foci, is quite rare and previous literature prevalently discusses unique locus of intramyometrial abscesses, usually treated with hysterectomy accompanied with or without bilateral salpingo oophorectomy. The presented case, to the authors' knowledge, is the first multiple myometrial abscess case treated with conservative surgical approach. PMID- 26152024 TI - The "How" and "When" of Parental Loss in Adulthood: Effects on Grief and Adjustment. AB - In order to evaluate the role of cause of death on the grief responses of parentally bereaved young and middle-aged adults, 400 individuals completed measures assessing their experiences and feelings surrounding the loss of a parent. Respondents included 247 young adults and 155 middle-aged adults. Cause of death was categorized as acute or anticipated with 209 participants reporting the parent's death as acute, while anticipated death was reported by 191 individuals. Results suggested that gender of the adult child and age level of the participant were important factors contributing to the grief response, and women were found to have more difficulty adjusting to the loss of a parent as well as demonstrating a more intense grief response. Young adults were found to be more impacted by the loss of a parent than were middle-aged adults. Those who were single or separated were similarly more impacted versus those who were married, where more young adults were single/separated and more middle-aged adults were married. Cause of death was only mildly influential in influencing responses to parental loss and did not interact with other studied variables. These results point to the importance of support from others in coping with a parent's death as well as for the counseling of bereaved persons who may be at risk for difficulties in coping with the death of a parent and enable a more precise understanding of individual grief processes across the adult lifespan. PMID- 26152025 TI - Online Memorialization and Grief After Suicide: An Analysis of Suicide Memorials on the Internet. AB - Although several studies have looked at the phenomenon of online memorialization, online involvement of those bereaved by suicide (suicide survivors) remains an under-studied area. The current study analyzed 250 memorials dedicated to those who died by suicide on two memorialization Web sites: Faces of Suicide and Gone too Soon. The majority of the memorials was posted by family members of the deceased and had a format of a letter or an obituary. Though the memorials were written for both males and females of all ages, 80% of the messages were written for young males. Fourteen themes were identified, ranging from sadness and expressions of love and other grief reactions of the bereaved, to acknowledgment of suicide and search for reasons for the death. Some of the bereaved wrote about their motives for posting an online memorial. Future studies should determine the impact of involvement in online memorialization on the grief process of suicide survivors. PMID- 26152026 TI - Attitudes and Practices in the Bereavement Care Offered by Children's Hospitals: A Survey of the Pediatric Chaplains Network. AB - Fifty thousand children die annually in the United States. No best practice standard exists regarding what services should be offered by children's hospitals to grieving families. We sought to identify the bereavement services most commonly offered, the departments primarily responsible for their dissemination, whether resources differ based on the patient's diagnosis or place of death, and whether the services offered are adequate. A 13-item anonymous online survey was emailed to 201 pediatric chaplains using the Pediatric Chaplains Network email list. Seventy respondents (34.8%) participated. Respondents described offering a variety of resources, but 47.8% of respondents believe the resources provided are not adequate. Increased staff and financial resources, and more consistency in services provided, were cited as needing improvement. The breadth and depth of bereavement services varies among children's hospitals. More studies are warranted to define the optimal approach to care for families grieving the loss of a child. PMID- 26152027 TI - The Ontological Representation of Death: A Scale to Measure the Idea of Annihilation Versus Passage. AB - Since the borders between natural life and death have been blurred by technique, in Western societies discussions and practices regarding death have became infinite. The studies in this area include all the most important topics of psychology, sociology, and philosophy. From a psychological point of view, the research has created many instruments for measuring death anxiety, fear, threat, depression, meaning of life, and among them, the profiles on death attitude are innumerable. This research presents the validation of a new attitude scale, which conjoins psychological dimensions and philosophical ones. This scale may be useful because the ontological idea of death has not yet been considered in research. The hypothesis is that it is different to believe that death is absolute annihilation than to be sure that it is a passage or a transformation of one's personal identity. The hypothetical difference results in a greater inner suffering caused by the former idea. In order to measure this possibility, we analyzed the correlation between Testoni Death Representation Scale and Beck Hopelessness Scale, Suicide Resilience Inventory-25, and Reasons for Living Inventory. The results confirm the hypothesis, showing that the representation of death as total annihilation is positively correlated to hopelessness and negatively correlated to resilience. PMID- 26152028 TI - Japanese Undergraduates' Attitudes Toward Students Survivors of Parental Suicide: A Comparison With Other Stigmatized Deaths. AB - This study investigated Japanese undergraduates' attitudes toward a fellow student whose parent has died by suicide. One hundred thirty-four participants responded to four versions of a brief fictional case describing a male undergraduate whose father had died. These presented fictional cases described the cause of the death as being suicide, cancer, AIDS, or murder. Results indicated that participants had more negative attitudes toward the suicide survivor student than the nonstigmatized death (cancer) survivor. Further, results indicated that participants viewed suicide survivors as more to blame for the death and had a more negative image of them than of the other stigmatized death (AIDS and murder) survivors. PMID- 26152029 TI - [ASSESSMENT OF POTENTIAL RISK FOR CONTAMINATION OF SURFACE WATER RESERVOIRS BY PATHOGENS OF HUMAN PARASITIC DISEASES]. AB - Sanitary and parasitological studies of the waste effluents and surface reservoir waters were conducted in the south of Russia. The efficiency of purification of waste effluents from the pathogens of parasitic diseases was investigated in the region's sewage-purification facilities. The water of the surface water reservoirs was found to contain helminthic eggs and larvae and intestinal protozoan cysts because of the poor purification and disinfection of service fecal sewage waters. The poor purification and disinvasion of waste effluents in the region determine the potential risk of contamination of the surface water reservoirs and infection of the population with the pathogens of human parasitic diseases. PMID- 26152030 TI - [PATHOGENS OF HUMAN TREMATODIASES IN THE PRIMORYE TERRITORY]. AB - The Primorye Territory of Russia is part of a natural habitat for pathogens of four human trematodiases: metagonimiasis (caused by the two worms Metagonimus yokogawai and M. katsuradai in the region), nanophyetiasis (Nanophyetus salmincola schikhobalowi), paragonimiasis (Paragonimus westermani ishunensis), and clonorchiasis (Clonorchis sinensis). The tensest situation in the region has emerged with clonorchiasis, the pathogen of which is extending its area due to anthropogenic sources. In addition to the above mentioned trematodes, the investigators have found 18 more species that may inhabit human beings. PMID- 26152031 TI - [THE ENVIRONMENTAL BASES AND MECHANISM FOR NATURAL OPISTHORCHIASIS FOCUS PULSATION IN THE COMBINED FOCUS OF OPISTHORCHIASIS AND TULAREMIA]. AB - A cyclic change in the epizootic activity of a tularemia activity underlies the mechanism of natural opisthorchiasis focus pulsation in the combined focus of opisthorchiasis and tularemia in the ecosystem of the Konda River. This is due to mass breeding and depression in the water vole (Arvicola terrestris) population. The mass breeding is predetermined by high population reproduction constants. The rodents' potential fecundity occurs with the high capacity of lands, which is caused by the hydrological regime of rivers. The size depression is predetermined by the epizootics of tularemia. The water vole is a host of the pathogens of opisthorchiasis and tularemia. So the mass rodent breeding in the combined infection and invasion focus causes an increase in the number of real invasion sources. The epizootic of tularemia is responsible for elimination of these invasion sources and for decreases in the flow of invasion material, the infection rate of Codiella and hence the amount of their produced cercarae, the extensive and intensive indicators of fish contamination, and the intensity of an epizootic process in the opisthorchiasis focus. PMID- 26152032 TI - [EPIZOOTOLOGICAL CHARACTERIZATION OF TREMATODIASIS FOCI IN THE ECOSYSTEM OF THE AMUR RIVER IN THE KHABAROVSK TERRITORY]. AB - Investigations were conducted in late June to early June 2013. The population density of mollusks of the genus Juga in the shoreline and littoral covered by meadow waters was 10 to 30 specimens/m2; there were solitary specimens of the genus Parafossarulus. Fourteen out of 39 fish species were invaded by metacercariae of Clonorchis. Manchurian spiny loaches (Leptobotia) and Light's bitterling (Rhodeus lighti) are first registered to be hosts of Clonorchis. The metacercariae of Metagonimus yokogawai were detected in silver carp (Hypophthalmichthys molitrix) and those of Nanophyetus salmincola schikhobalowi were in the kidneys, fin muscles, and gills of taimen (Hucho) and lenok (Brachymystax lenok) from the Khor River. The invasion rate for the taimen was greater than 1000 metacercariae and that for the lenok was not more than 720 metacercariae per fish. PMID- 26152033 TI - [AEROMONAS BACTERIA ISOLATED FROM BITHYNIIDAE MOLLUSKS AND THEIR HABITATS: SPECIES COMPOSITION AND BIOLOGICAL PROPERTIES. COMMUNICATION 1]. AB - The purpose of this investigation was to study the species composition and biological properties of Aeromonas bacteria isolated from Bithyniidae mollusks and their habitat (a water reservoir). The Bithyniidae mollusks and water from their habitat were the material to be studied. A total of 176 Aeromonas strains were isolated from the mollusks and water. A. veronii, A. hydrophila, and A. ichthiosmia were most common in the mollusks and A. veronii and A. ichthiosmia were in the water. All the strains isolated had hemolytic activity and no lysozyme or plasma coagulase activity. The magnitude of lecithinase and antilysozymic activities and biofilm formation of the Aeromonas bacteria varied with the isolation source of their strains. PMID- 26152034 TI - [THE STRUCTURE AND SOME BIOLOGICAL PROPERTIES OF GRAM-NEGATIVE BACTERIA CONSTITUTING THE MICROSYMBIOCENOSIS OF PROSOBRANCHIA MOLLUSKS (BITHYNIIDAE). COMMUNICATION 2]. AB - The goal of this investigation was to study the structure and biological properties (antilysozymic, activity and biofilm formation) of gram-negative bacteria isolated from Bithyniidae mollusks and their habitat (water reservoir waters and soil). A total of 160 gram-negative bacterial strains isolated from the mollusks of the Bithyniidae family and their habitat were the material to be, studied. Psedomonas, Comamonas, and Acinetobacter held the lead in the structure of microbiocenosis of Bithyniidae mollusks, the first intermediate host of Opisthorchis filineus, while Acinetobacter did in the habitat. The antilysozymic activity of the water strains was shown to be an order of magnitude higher than that of the strains isolated from the mollusks. PMID- 26152035 TI - [RIBOSOMAL DNA INTERNAL TRANSCRIBED SPACER 2 SEQUENCE AS A PHYLOGENETIC MARKER FOR THE IDENTIFICATION OF TRICHINELLA NEMATODES]. AB - The results of testing several primer combinations were used to choose an optimal pair for the amplification of the internal transcribed spacer 2 (ITS2) region of ribosomal DNA (direct: Tri58s F 5 CGG TGG ATC RCT TGG CTC GTA CG and reverse: AB28 Rr (CGA CCG CTT ATT GAT ATG C). This pair of primers yields a 900 bp PCR product. Comparative analysis of obtained ITS2 sequences, for 8 Trichinella isolates from different regions of the Russian Federation permits different species and individual genotypes of these parasitic nematodes to be validly distinguished. PMID- 26152036 TI - [MORPHOLOGICAL CHANGES IN THE STRIATED MUSCLES AFTER ALBENDAZOLE TREATMENT FOR EXPERIMENTAL TRICHINOSIS]. AB - Trichinosis was experimentally induced in rats. The morphology of encystation of Trichinella larvae was studied in the striated muscles. The efficacy of albendazole was evaluated in different intensity of Trichinella larvae infestation in the striated muscles of the laboratory animals. Encystation was shown to cease at 21 days. Albendazole showed high activity against intestinal and encapsulated larvae of Trichinella, leading to 100% death of T. spiralis. Capsules and Trichinella larvae were described to be destructed after treatment with albendazole 15 mg/kg twice daily for 10 days. PMID- 26152037 TI - [POSSIBILITY FOR LUMINESCENCE IDENTIFICATION OF DIFFERENT TRICHOMONAS VAGINALIS FORMS]. AB - The paper presents the results of examining the morphology of different forms of Trichomonas vaginalis by indirect immunofluorescence. Fluorescence microscopy revealed that the typical forms of vaginal trichomonads showed a very bright light green glow, around the periphery of a cell in particular; the atypical forms of trichomonads emitted in the green spectral region less brilliantly and evenly. Trichomonas fluorescence intensity was measured by spectrofluorescence assay. The experimental findings point to the fact that the fluorescence rate of typical forms, of Trichomonas is 2-4 times higher than that of its forms with atypical morphology. PMID- 26152038 TI - [Preparation of the salicylanilide MST-28 and investigation of its antihymenolepic activity]. PMID- 26152039 TI - [THE DEVELOPMENT AND SURVIVAL OF TOXOCARA CANIS EGGS IN THE NATURAL CLIMATIC CONDITIONS OF GORNO-ALTAISK]. AB - The time of development and survival of Toxocara canis eggs in the soil of Gorno Altaisk was experimen- tally investigated in 2011-2014. In July 2011, T.canis eggs matured at 3-5-cm soil depths from the stage of 1-2 blastomeres to invading larva within 12 days at a daily average temperature of +23 degrees C and at a relative humidity of 82%. At 3-5-cm soil depths, more than 70% of invaded T. canis eggs preserved their viability through- out the experimental period (4 years). The paper gives evidence for the seasonal survival of invaded T. canis eggs in relation of the length of soil stay. PMID- 26152040 TI - [PEDICULOSIS: CURRENT ASPECTS OF THE OLD PROBLEM]. AB - Analysis of data on the incidence of pediculosis worldwide has shown that this disease still remains one of the major health problems in many countries. The ways of transmitting lice and different (social and biological) factors influencing lice infestation are considered. The country's real morbidity rate, such as the ratio of the number of reported pediculosis cases to the amount of pediculicides sold at drugstores in both Russia as a whole and its individual federal districts in particular, has been investigated. The actual morbidity rate has been found to be higher than the officially recorded one. PMID- 26152041 TI - [Geohelminthiases in the Russian Federation]. PMID- 26152042 TI - [THE FUNCTIONAL CONSTITUENT OF A BIOLOGICAL COMPONENT IN PROGRAMS FOR TRAINING SPECIALISTS IN THE AREA OF PARASITOLOGY FOR ACCREDITATION]. AB - The paper considers the functional aspects of a biological component in programs for training specialists in the area of Parasitology for accreditation within the current enactments, including those on modernization of public health and additional professional education. The working program of the module "Fundamental Disciplines" has been used as an example to outline approaches to molding a medical parasitologist's capacity and readiness to solve professional tasks on the basis of knowledge of fundamental disciplines: biology, immunology, and medical geography. Education fundamentalization is shown to suggest more unsupervised work of a learner in the teaching process. The fundamental constituent of a biological component of the 'programs for training learners in the specialty of Parasitology for accreditation is shown in the interaction of all sections of this area with special and allied subjects. PMID- 26152043 TI - [METHODOLOGICAL APPROACHES TO DEFINING CRITERIA FOR ACCREDITATION OF SPECIALISTS (IN CASE OF MEDICAL PARASITOLOGISTS)]. AB - In 2016, provision is made for the transition for an accreditation system for all health workers to have individual permits for specific kinds of medical activities. Regular accreditation of health workers is one of the constituents of medical education, which is being intensively elaborated by the Ministry of Health of Russia jointly with a professional community by the module principle of using an accumulation system of valid credits. Despite the fact that higher educational establishments belong to different agencies, educational programs for physicians, criteria and procedures for their accreditation must be uniform. In this connection, there is today's challenge of methodological and methodical approaches to defining criteria for the accreditation of specialists of healthcare facilities of the Ministry of Health of Russia, bodies and institutions of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare. In the context of systemic and functional methodological approaches, the paper shows a procedure for defining criteria for the accreditation of specialists (in case of medical parasitologists). PMID- 26152044 TI - Antioxidant properties of fermented mango leaf extracts. AB - Antioxidant properties of mango (Mangifera indica) leaves were evaluated. Hydroalcoholic leaf extracts that were lyophilized were subsequently fermented with either Lactobacillus casei or effective microorganisms (EM) such as probiotic bacteria and/or other anaerobic organisms. Antioxidant properties were measured as a function of the mango leaf extract concentration in the fermentation broth. Tests for radical scavenging using the 1,1-diphenyl-2 picrylhydrazyl radical showed higher antioxidant activity for Lactobacillus- and EM-fermented mango leaf extracts than for the synthetic antioxidant butylated hydroxytoluene. Antioxidant activity generally increased with increasing fermented extract concentration as did the fermented extracts' polyphenol and flavonoid contents. Fermented extracts reduced reactive oxygen species generation by lipopolysaccharide in RAW 264.7 cells when measured via fluorescence of dichlorodihydrofluorescein acetate treated cells using flow cytometry. RAW 264.7 cells also showed a concentration-dependent cytotoxic effect of the fermented extracts using the 3-(4,5-dimethylthialol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Inhibition of mushroom tyrosinase activity as well as nitrite scavenging by the fermented extracts increased as fermented extract concentrations increased. Tyrosinase activity was assayed with 3,4 dihydroxyphenylalanine as substrate. Nitrite scavenging was assessed via measurement of inhibition of chromophore production from nitrite-naphthylamine sulfanilic acid mixtures. The antioxidant properties of fermented mango leaf extracts suggest the fermented extracts may be useful in developing health food and fermentation-based beauty products. PMID- 26152045 TI - New aspects of the structure of human hair on the basis of optical microscopic observations of disassembled hair parts. AB - Infant' and adult' scalp hair fibers were disassembled to various cellular components and blocks by chemical and enzymatic treatments, followed by random scission with rapidly rotating cutters. The hair fibers were also fractured by the use of a vise. The optical microscopic inspection of these specimens led to the discovery of many previously unknown structures in the hair shaft. In particular, a cuticular cell (Cu) was found to take a trowel-like shape consisting of a part with a blade-like shape (CuB) and a part with a handle-like shape (CuH), where CuB overlapped one another and fused partially to build the honeycomb-like structure on a large cuticular thin plate (CuP). Whereas CuH was closely similar to the cortical cell in dimensions and richness of macrofibrils (Mf). It was considered that human hair is stabilized structurally and physicochemically by the presence of the honeycomb-like structure, the CuP and the Mf. PMID- 26152046 TI - Prediction of bending set, wave efficacy, and hair damage using an extensional permanent waving treatment and the 20% index value. AB - To predict "wave efficacy" as evaluated by hairdressers, an extensional permanent waving treatment was performed on human hair fibers using various wave lotions manufactured in Japan. Glass columns devised for the purpose were equipped with a tensile tester in order to increase the measurement accuracy. Notably, the observed set agreed with the theoretical set. In addition, the data for the extensional set exhibited good correlation with the bending set and the wave efficacy assessed in a beauty parlor, and hair damage was estimated by the characteristic change in the 20% index. The following facts were experimentally determined. First, the Young's modulus of the hair fibers after extensional permanent waving treatment continually decreased with an increase in the reduction of the fibers and then abruptly decreased at 80% reduction. Second, the reduction of hair treated with the ammonium salt of thioglycolic acid followed pseudo first-order kinetics only during the initial stage of the reaction, independent of the pH level. Third, the 20% index of the individual virgin hairs remained constant in water at 30 degrees C and also correlated with the Young's modulus of the hair after extensional permanent waving treatment. PMID- 26152047 TI - Temporal variations in sirtuin expression under normal and ultraviolet B-induced conditions and their correlation to energy levels in normal human epidermal keratinocytes. AB - Sirtuins are post-translational modifiers that affect transcriptional signaling, metabolism, and DNA repair. Although originally identified as gene silencers capable of extending cell lifespan, the involvement of sirtuins in many different areas of cell biology has now become widespread. Our approach has been to study the temporal variation and also the effect of environmental stressors, such as ultraviolet B (UVB) and ozone, on sirtuin expression in human epidermal keratinocytes. In this report, we measured the variation in expression of several sirtuins over time and also show how a low dose of UVB can affect this pattern of expression. Moreover, we correlated these changes to variations in hydrogen peroxide (H2O2) and ATP levels. Our data show significant variations in normal sirtuin expression, which may indicate a generalized response by sirtuins to cell cycle kinetics. These results also demonstrate that sirtuins as a family of molecules are sensitive to UVB-induced disruption and may suggest a new paradigm for determining environmental stress on aging and provide direction for the development of new cosmetic products. PMID- 26152048 TI - Cadmium, Lead and Nickel in Hair Care Products in Turkey. PMID- 26152049 TI - Spatial Frequency Modulates the Degree of Illusory Second Flash Perception. AB - When a brief single flash is presented simultaneously with two brief beeps, the number of presented flashes is often perceived as two. This phenomenon is referred to as the fission illusion. Several effects related to the fission illusion have been investigated using both psychophysical and neurophysiological methods. The present study examined the effects of spatial frequency on the fission illusion. At a low spatial frequency, transient channels respond preferably; conversely, sustained channels respond preferably at a high spatial frequency. Sustained channels differ in temporal properties from transient channels and are characterized by poor temporal resolution and slow-onset responses. In our previous study, visual stimuli presented at a slow processing speed were not conducive to the fission illusion. Therefore, we hypothesized that the fission illusion would not be difficult to observe when using high spatial frequencies. The results indicated that the degree of the perceived illusory second flash was reduced when spatial frequency was high as compared to when it was is low. Furthermore, according to signal detection theory, this difference between high and low spatial frequencies was not attributed to participants' response biases. Therefore, the fission illusion likely will not occur in conditions of slow processing speed and long response latencies in sustained channels, which respond preferably to high spatial frequency stimuli. Overall, the results indicated that the fission illusion was affected by temporal characteristics of lower-order sensory processing stages. PMID- 26152051 TI - Introduction to the Special Issue on Multisensory Development and Plasticity. PMID- 26152050 TI - Visual-Somatosensory Integration is Linked to Physical Activity Level in Older Adults. AB - Studies examining multisensory integration (MSI) in aging consistently demonstrate greater reaction time (RT) facilitation in old compared to young adults, but often fail to determine the utility of MSI. The aim of the current experiment was to further elucidate the utility of MSI in aging by determining its relationship to physical activity level. 147 non-demented older adults (mean age 77 years; 57% female) participated. Participants were instructed to make speeded responses to visual, somatosensory, and visual-somatosensory (VS) stimuli. Depending on the magnitude of the individuals' RT facilitation, participants were classified into a MSI or NO MSI group. Physical activity was assessed using a validated physical activity scale. As predicted, RTs to VS stimuli were significantly shorter than those elicited to constituent unisensory conditions. Multisensory RT facilitation was a significant predictor of total number of physical activity days per month, with individuals in the NO MSI group reporting greater engagement in physical activities compared to those requiring greater RT facilitation. PMID- 26152052 TI - Unraveling Cross-Modal Development in Animals: Neural Substrate, Functional Coding and Behavioral Readout. AB - The interaction of every living organism with its environment relies on sensory abilities. Hence, sensory systems need to develop rapidly and early in life to guarantee an individual's survival. Sensors have to emerge that are equipped with receptors that detect a variety of stimuli. These sensors have to be wired in basic interconnected networks that possess the ability to process the uni- as well as multisensory information encoded in the sensory input. Plastic changes to refine and optimize these circuits need to be effected quickly during periods of sensory experience so that uni- and multisensory systems can rapidly achieve the functional maturity needed to support the perceptual and behavioral functions reliant upon them. However, the requirement that sensory abilities mature quickly during periods of enhanced neuroplasticity is at odds with the complexity of sensory networks. Neuronal assemblies within sensory networks must be precisely wired so that processing and coding mechanisms can render relevant stimuli more salient and bind features together appropriately. Focusing on animal research, the first part of this review describes mechanisms of sensory processing that show a high degree of similarity within and between sensory systems and highlight the network complexity in relationship to the temporal and spatial precision that is needed for optimal coding and processing of sensory information. Given the resemblance of most adult intra- and intersensory coding mechanisms, it is likely that their developmental principles are similar. The second part of the review focuses on developmental aspects, summarizing the mechanisms underlying the emergence and refinement of precisely coordinated neuronal and multisensory functioning. For this purpose, we review animal research that elucidates the neural substrate of multisensory development applicable to, the less accessible, human development. Animal studies in this field have not only complemented human studies, but brought new ideas and numerous cutting edge conclusions leading to the discovery of common principles and mechanisms. PMID- 26152053 TI - Multisensory Integration and Calibration in Children and Adults with and without Sensory and Motor Disabilities. AB - During the first years of life, sensory modalities communicate with each other. This process is fundamental for the development of unisensory and multisensory skills. The absence of one sensory input impacts on the development of other modalities. Since 2008 we have studied these aspects and developed our cross sensory calibration theory. This theory emerged from the observation that children start to integrate multisensory information (such as vision and touch) only after 8-10 years of age. Before this age the more accurate sense teaches (calibrates) the others; when one calibrating modality is missing, the other modalities result impaired. Children with visual disability have problems in understanding the haptic or auditory perception of space and children with motor disabilities have problems in understanding the visual dimension of objects. This review presents our recent studies on multisensory integration and cross-sensory calibration in children and adults with and without sensory and motor disabilities. The goal of this review is to show the importance of interaction between sensory systems during the early period of life in order to correct perceptual development to occur. PMID- 26152054 TI - Two-Dimensional Rubber-Hand Illusion: The Dorian Gray Hand Illusion. AB - The rubber-hand illusion provides a window into body representation and consciousness. It has been found that body-ownership extended to numerous hand like objects. Interestingly, the vast majority of these objects were three dimensional. We adopted this paradigm by using hand drawings to investigate whether rubber-hand illusion could be extended to two-dimensional hand samples, and we measured skin conductance responses and behavioural variables. The fact that this illusion extended to two-dimensional stimuli reveals the dominant role of top-down information on visual perception for body representation and consciousness. PMID- 26152055 TI - Task-Specific, Age Related Effects in the Cross-Modal Identification and Localisation of Objects. AB - We investigated age-related effects in cross-modal interactions using tasks assessing spatial perception and object perception. Specifically, an audio-visual object identification task and an audio-visual object localisation task were used to assess putatively distinct perceptual functions in four age groups: children (8-11 years), adolescents (12-14 years), young and older adults. Participants were required to either identify or locate target objects. Targets were specified as unisensory (visual/auditory) or multisensory (audio-visual congruent/audio visual incongruent) stimuli. We found age-related effects in performance across both tasks. Both children and older adults were less accurate at locating objects than adolescents or young adults. Children were also less accurate at identifying objects relative to young adults, but the performance between young adults, adolescents and older adults did not differ. A greater cost in accuracy for audio visual incongruent relative to audio-visual congruent targets was found for older adults, children and adolescents relative to young adults. However, we failed to find a benefit in performance for any age group in either the identification or localisation task for audio-visual congruent targets relative to visual-only targets. Our findings suggest that visual information dominated when identifying or localising audio-visual stimuli. Furthermore, on the basis of our results, object identification and object localisation abilities seem to mature late in development and that spatial abilities may be more prone to decline as we age relative to object identification abilities. In addition, the results suggest that multisensory facilitation may require more sensitive measures to reveal differences in cross-modal interactions across higher-level perceptual tasks. PMID- 26152056 TI - Audio-Visual Stimulation Improves Visual Search Abilities in Hemianopia due to Childhood Acquired Brain Lesions. AB - Results obtained in both animal models and hemianopic patients indicate that sound, spatially and temporally coincident with a visual stimulus, can improve visual perception in the blind hemifield, probably due to activation of 'multisensory neurons', mainly located in the superior colliculus. In view of this evidence, a new rehabilitation approach, based on audiovisual stimulation of visual field, has been proposed, and applied in adults with visual field reduction due to unilateral brain lesions. So far, results have been very encouraging, with improvements in visual search abilities. Based on these findings, we have investigated the possibility of inducing long-lasting amelioration also in children with a visual deficit due to acquired brain lesions. Our results suggest that, in the absence of spontaneous recovery, audiovisual training can induce activation of visual responsiveness of the oculomotor system also in children and adolescents with acquired lesions and confirm the putatively important role of the superior colliculus (SC) in this process. PMID- 26152057 TI - Movement Induces the Use of External Spatial Coordinates for Tactile Localization in Congenitally Blind Humans. AB - To localize touch, the brain integrates spatial information coded in anatomically based and external spatial reference frames. Sighted humans, by default, use both reference frames in tactile localization. In contrast, congenitally blind individuals have been reported to rely exclusively on anatomical coordinates, suggesting a crucial role of the visual system for tactile spatial processing. We tested whether the use of external spatial information in touch can, alternatively, be induced by a movement context. Sighted and congenitally blind humans performed a tactile temporal order judgment task that indexes the use of external coordinates for tactile localization, while they executed bimanual arm movements with uncrossed and crossed start and end postures. In the sighted, start posture and planned end posture of the arm movement modulated tactile localization for stimuli presented before and during movement, indicating automatic, external recoding of touch. Contrary to previous findings, tactile localization of congenitally blind participants, too, was affected by external coordinates, though only for stimuli presented before movement start. Furthermore, only the movement's start posture, but not the planned end posture affected blind individuals' tactile performance. Thus, integration of external coordinates in touch is established without vision, though more selectively than when vision has developed normally, and possibly restricted to movement contexts. The lack of modulation by the planned posture in congenitally blind participants suggests that external coordinates in this group are not mediated by motor efference copy. Instead the task-related frequent posture changes, that is, movement consequences rather than planning, appear to have induced their use of external coordinates. PMID- 26152058 TI - Neural Correlates of Human Echolocation of Path Direction During Walking. AB - Echolocation can be used by blind and sighted humans to navigate their environment. The current study investigated the neural activity underlying processing of path direction during walking. Brain activity was measured with fMRI in three blind echolocation experts, and three blind and three sighted novices. During scanning, participants listened to binaural recordings that had been made prior to scanning while echolocation experts had echolocated during walking along a corridor which could continue to the left, right, or straight ahead. Participants also listened to control sounds that contained ambient sounds and clicks, but no echoes. The task was to decide if the corridor in the recording continued to the left, right, or straight ahead, or if they were listening to a control sound. All participants successfully dissociated echo from no echo sounds, however, echolocation experts were superior at direction detection. We found brain activations associated with processing of path direction (contrast: echo vs. no echo) in superior parietal lobule (SPL) and inferior frontal cortex in each group. In sighted novices, additional activation occurred in the inferior parietal lobule (IPL) and middle and superior frontal areas. Within the framework of the dorso-dorsal and ventro-dorsal pathway proposed by Rizzolatti and Matelli (2003), our results suggest that blind participants may automatically assign directional meaning to the echoes, while sighted participants may apply more conscious, high-level spatial processes. High similarity of SPL and IFC activations across all three groups, in combination with previous research, also suggest that all participants recruited a multimodal spatial processing system for action (here: locomotion). PMID- 26152060 TI - ASSESSMENT OF THE SEXUAL FUNCTION AFTER RECTAL CANCER SURGERY. AB - INTRODUCTION: Introduction: Sexual functioning is one of the most important components of subjective term quality of life. The growing incidence of rectal cancer recent decades lead to a tendency to optimize the diagnostic and therapeutic process, to perform better staging and postoperative disease control. Clearing the operational plan to achieve radicality and preservation of pelvic autonomic innervation are key components affecting sexual function and subsequent quality of life of patients. MATERIALS AND METHODS: It was used data from questionnaires QLQ C30 and QLQ C38 to assess sexual function, according to the methodology of the EORTC (European Organization for Research and Treatment of Cancer). Information was collected of 71 patients operated and monitored in Complex Cancer Center of Veliko Tarnovo during the period 01.2005-06.2010 year. It compares 38 underwent sphincter-sparing operations and 33 abdominoperineal resections having definitive stoma. Patients had fulfilled questionnaires more than six full months after surgery forming a functional scale related to sexual function. RESULTS: A significantly higher number men after abdominoperineal resection have trouble to ejaculate compared to patients after anterior resection of the rectum. Statistically significant difference in sexual function between studied groups was observed in the male sex. CONCLUSION: The psychometric values of the self-perception of health were highest after treatment of high rectal carcinomas. Sphincter-spared men after rectal resection had significant fewer problems with ejaculation, compared with patients suffered abdominoperinealna cutter. Sexual dysfunction was significantly more common in men underwent rectum extirpation compared to patients undergoing conservative surgery. PMID- 26152059 TI - EPIDEMIOLOGICAL REGISTRY OF NEUROENDOCRINE TUMORS IN BULGARIA--A PILOT SURVEY. AB - The National registry of patients with neuroendocrine tumors (NET) in Bulgaria was established in 2013 as a joint initiative of the Bulgarian Surgical Society and the Institute for Rare Diseases. The register aims to explore the epidemiology of NET in Bulgaria, as well as the different diagnostic and treatment approaches for the disease throughout the country. This the first of its kind retrospective study of NET in the country is covering the period January 2012 - January 2013. A total of 127 patients with NET were identified. At the time of the survey the average age of patients with NET was 58.61 +/- 15.59 years. The data show almost equal distribution between the genders with a slight predominance of women. The largest relative part of NET is those of NET located in the gastrointestinal tract (54.10 +/- 4.51%), followed by those located in the pancreas (12.30 +/- 2.97%) and in the lungs (10.66 +/- 2.79%). In 72.44 +/- 3.96% of the patients a immunohistochemical diagnosis was performed. The study confirmed the leading role of the surgery method of the NET management. In 65.83 +/- 4.33% of the patients a radical removal of the tumor was conducted, while the relative part of the undertaken partial resection was 7.50 +/- 2.40%. A statistically significant association between the type of surgical treatment and during the follow-up of patients was found. An update of the information in the register will allow a more precise determining of the distribution and management of NET in Bulgaria. PMID- 26152061 TI - AN APPROACH TO THE DETERMINATION OF A PROGNOSTIC INDEX FOR THE SCOPE OF SIMULTANEOUS RESECTION IN PATIENTS WITH SYNCHRONOUS COLORECTAL LIVER METASTASES. AB - Based on the results of 62 simultaneous operations in patients with synchronous liver metastases from colorectal cancer, an attempt was made to calculate the index, assisting the surgeon in the selection of the liver resection, considering the sensitivity and specificity of the test. The index is calculated using equations based on variables and their coefficients from Cox regression analysis. The type of surgery is associated with prognosis for survival of the operated patients. The results can serve as a basis for further research in this area. PMID- 26152062 TI - USAGE OF VACUUM ASSISTED TECHNOLOGY IN A NEWBORN WITH OMPHALOCELE. AB - Omphalocele is a congenital abdominal wall defect. The treatment is surgical on one or multiple stages for the giant forms of the anomaly. It is a challenge for the pediatric surgeons while omphalocele is a giant one and it is impossible to insert all the organs in the abdominal cavity. The treatment and the hospitalization of the child are quite long. The authors present a case--a newborn with a omphalocele and share their experience. This method gives good results, shorten the treatment and the stay in hospital. PMID- 26152063 TI - IS THERE A ROOM IN BULGARIA FOR RADIOTHERAPY OF GASTRIC CANCER? AB - Gastric cancer is the fourth most common cancer worldwide with one million new casesyearly and the second most frequent cause of cancer death. Although surgery is the leading treatment modality of gastric cancer the survival remains low (5- year survival is reported to be 25% in Europe and 60% in the Eastern world). The risk of locoregional recurrence grows with the increase of the tumor stage. In order to improve locoregional control a number of clinical studies in the last four decades have examined different strategies of adjuvant therapy, including chemotherapy, radiotherapy, chemoradiation with ambiguous results. Various regimens of radiotherapy alone, applied preand postoperatively or in combination with chemotherapy in pre- and postoperative settings have been studied. With the present article, the authors present the world experience of radiotherapy application in gastric carcinoma, supporting its introduction in to Bulgarian clinical practice. The study results concerning this topic have been discussed. SWOG/Intergroup 0116 study showed that postoperative chemoradiation leads to increased 5-year overall survival compared with surgery alone. A recent metaanalysis on randomized trials in operable gastric cancer, found that adjuvant radiotherapy leads to 20 % improvement in disease free survival and overall survival and found no subgroup of patients who do not benefit from adjuvant radiotherapy. The available data from the published studies and metaanalysis completely supports the introduction of chemoradiation for gastric cancer and in Bulgarian radiotherapy practice with the opportunity of gaining own experience. PMID- 26152064 TI - ANESTHESIA CHARACTERISTICS OF A PATIENT WITH HYPERKALEMIC PERIODIC PARALYSIS- CASE REPORT. AB - We report a case of a successfully conducted anesthesia, without complications of a patient with hyperkalemic periodic paralysis who underwent elective laparoscopic cholecystectomy for chronic calculous cholecystitis. The perioperative considerations, the characteristics of anesthesia, and the factors that can lead to complications in this rare genetic disorder are discussed. PMID- 26152065 TI - COMPARATIVE ANALYSIS OF THE FOUR-PORT AND THE THREE-PORT TROCAR ACCESS AND THE SINGLE PORT ACCESS IN LAPAROSCOPIC CHOLECYSTECTOMY--REVIEW OF THE LITERATURE. AB - INTRODUCTION: In the last few years, the search for less invasive procedures led to the development of the innovative technologies of SILS (Single incision laparoscopic surgery) and NOTES (Natural orifice translumenal endoscopic surgery). Lately, SILS's popularity increased in the same manner as the laparoscopic cholecystectomy did in the early 90's of the last century. AIM: The aim of this analysis is to review the studies, focused on the indications for applying the different techniques of the single-port laparoscopic cholecystectomy, their advantages and disadvantages and the future guidelines for the development of the new trocar access surgical techniques. METHODOLOGIES AND MATERIALS: The studies of the decision making process for applying a certain surgical technique of the conventional laparoscopic cholecystectomy and the single-port laparoscopic cholecystectomy were reviewed. The different aspects of both techniques were analyzed and to demonstrate their relevance, have been illustrated by the published by 2012 studies. RESULTS: The review of the literature spams over 37 articles, which compare the two main techniques for conventional laparoscopic cholecystectomy in the following parameters: age, BMI, safety of the technique, technical parameters of the surgical intervention as access facilitation, surgery duration, blood loss, postoperative pain, the duration of the hospitalization, the time needed for physical recuperation, short term and long-term cosmetic results, esthetic satisfaction of the patient and medical and social effectiveness. The reviewed studies didn't show a significant advantage of any of those two techniques. In most cases though, the duration of the hospitalization was shorter for patients that underwent single-port laparoscopic cholecystectomy. The single-port laparoscopic cholecystectomy shows better results in postoperative pain and esthetic results as well. PMID- 26152066 TI - IMAGES OF NATURE. PMID- 26152067 TI - TRANSATLANTIC VIEWS OF NATURE. PMID- 26152068 TI - " MILIEU ", " ENVIRONMENT ", AND " SYSTEM ": THE TRANSFORMATIONS OF THEORETICAL TERMS IN SCIENCE, FROM MODERN TO CONTEMPORARY. PMID- 26152069 TI - [Happiness and virtue: the education of the individual at the beginning of modernization]. PMID- 26152070 TI - [From Happiness ideation to quality of life concept]. PMID- 26152071 TI - [Towards quality of life: emergence of Sciences and Technology]. PMID- 26152072 TI - DEBATING QUALITY OF LIFE TODAY. PMID- 26152073 TI - TEMPERANCE AS AN ENVIRONMENTAL VIRTUE. AN INTERPRETATION OF THOMAS AQUINAS IN A "GREEN PERSONALISM" PERSPECTIVE. PMID- 26152074 TI - RETHINKING CREATION IN THE ECOLOGICAL CRISIS. PMID- 26152075 TI - FEELING NATURE: EMOTIONS AND ECOLOGY. THE LEGACY OF ROMANTICISM. PMID- 26152076 TI - MEDICINE AND ECOLOGY: HISTORICAL AND CRITICAL PERSPECTIVES ON THE CONCEPT OF 'EMERGING DISEASE'. PMID- 26152077 TI - IS THE EARTH SICK? PMID- 26152079 TI - TECHNOLOGY AND HUMAN NATURE. PMID- 26152080 TI - SUSTAINABLE DEVELOPMENT FOR A CAPABLE FUTURE SOCIETY. PMID- 26152081 TI - FOOD PHILOSOPHIES AND SUSTAINABLE QUALITY OF LIFE. PMID- 26152082 TI - HOW MUCH BIODIVERSITY DO WE NEED? PMID- 26152083 TI - [Society face to cancer: awareness and social actions]. PMID- 26152084 TI - [Maintenance chemotherapy: futility or utility?]. AB - In incurable diseases, maintenance therapy aims to prolong the response achieved through induction. The goal is to delay disease progression, thus prolonging survival. Two maintenance modalities are used. The first, called continuation maintenance, consists of continuing the same agent used in the initial treatment. The second, called switch-maintenance, introduces an early second line drug immediately after induction. Proving the superiority of a maintenance strategy implies a better outcome with the maintenance compared to the same therapeutic agent used upon disease progression. This benefit may be observed in terms of overall survival and/or quality of life. PMID- 26152085 TI - [New melanoma immunotherapies: mechanisms of action, efficiency and management of toxicities]. AB - In recent years the therapy of metastatic melanoma has been revolutionized from a disease with very few efficient treatment options to one with access to multiple therapies which can impact on patient survival. Two main classes of therapies have been developed: 1. Immunotherapy by immune checkpoint inhibitors and 2. Small molecule inhibitors of the MAPK pathway. Immunotherapies achieved by either inhibition of CTLA-4 or the PD1/PD-Ll axes are impacting the overall survival in an important fraction of patients. In addition, the side effects of these immune therapy approaches require early detection by all the specialists involved as well as early management according to precise guidelines for optimal outcome. PMID- 26152086 TI - [Current perspectives on supportive care for lung cancer patients]. AB - The fight against cancer comprises not only survival of the disease but also survival with the highest possible quality of life. Thus, supportive care in cancer aims at reducing physical and psycho-emotional symptom burden. Furthermore, supportive care in cancer includes self-management-support for patients and their families/caregivers. Due to high symptom prevalence and poor prognosis, lung cancer patients express more unmet supportive care needs than other patient populations with cancer. Interventions to meet these needs have been developed in the last decade. They involve new models of care that incorporate the role of a lung cancer nurse in comprehensive cancer centers and eHealth-systems to support lung cancer patients and their families/caregivers. PMID- 26152087 TI - [News and perspectives in the treatment of advanced gastric and colorectal cancers]. AB - Colorectal and gastric cancers are the fourth and third leading causes of cancer death world-wide. Unfortunately, gastric cancer is usually diagnosed at an advanced stage after becoming metastatic in distant sites, so that palliative therapy is the mainstay of treatment. Major progress in the understanding of the biology, the development of valid biomarkers and molecular targeted drugs have improved the treatment options and prognosis of both cancers significantly in the last years. Here, we review the current standards of care for patients with advanced and metastatic colorectal and gastric cancer and outline the perspectives for the future. PMID- 26152088 TI - [Early oesophageal cancer: epidemiology diagnosis and management]. AB - In Europe, oesophageal cancers are diagnosed at an early stage in less than 10% of the cases. They are superficial tumours whose invasion is limited to the mucosae and the submucosa. Synchronous node invasion is the most important prognosis factor. Oesophagectomy is the benchmark treatment. Nowadays, endoscopic resection is a validated curative therapeutic alternative. Accurate endoscopic evaluation using chemical or virtual colouring as well as an echoendoscopy, followed by an expert pathological review, must be conducted beforehand. It can be realised for good prognosis tumours after evaluation of the synchronous node invasion or its risk. After completion, regular endoscopic follow-ups are compulsory to detect local relapse. PMID- 26152089 TI - [Doctor, I'm hot! Managing the effects of menopause in patients with breast cancer]. AB - The incidence of breast cancer is rising up, but the mortality rate is decreasing, leading to a growing number of survivors. Most of these women are postmenopausal at diagnosis or will reach menopause following anti-cancer treatments. Most of them have hormone-sensitive tumors and will receive an anti hormonal treatment. Endocrine therapy is associated with many adverse effects, including a worsening of climacteric symptoms with a negative impact on quality of life and therefore a suboptimal therapeutic adherence. Some supportive therapies can alleviate these adverse effects and should be offered to patients. PMID- 26152090 TI - [Testicular cancer: a model to optimize the radiological follow-up]. AB - Despite being rare cancers, testicular seminoma and non-seminoma play an important role in oncology: they represent a model on how to optimize radiological follow-up, aiming at a lowest possible radiation exposure and secondary cancer risk. Males diagnosed with testicular cancer undergo frequently prolonged follow-up with CT-scans with potential toxic side effects, in particular secondary cancers. To reduce the risks linked to ionizing radiation, precise follow-up protocols have been developed. The number of recommended CT scanners has been significantly reduced over the last 10 years. The CT scanners have evolved technically and new acquisition protocols have the potential to reduce the radiation exposure further. PMID- 26152091 TI - [Advanced hepatocellular carcinoma: importance of clinical trials]. AB - In hepatocellular carcinoma, sorafenib is the only active medical treatment validated to date. Sorafenib is a targeted therapy mainly blocking tumor vascularisation. Sorafenib is currently used for inoperable or advanced stages of hepatocellular carcinoma, as well for hepatocellular carcinoma recurrence when the disease is diffuse or multifocal. Current clinical trials are designed to identify new antitumor molecules active in hepatocellular carcinoma that could enrich the therapeutic armamentarium in addition to sorafenib. PMID- 26152092 TI - ["Artificial" spermatozoa: next step in assisted reproduction?]. PMID- 26152093 TI - [Hospital admission]. PMID- 26152094 TI - [Ebola: WHO's disorganization is established officially]. PMID- 26152095 TI - [Varenicline to stop smoking progressively]. PMID- 26152096 TI - [Miscellaneous news in biology, virology and esthetics]. PMID- 26152097 TI - [Influenza: 2015 epidemic is responsible for mortality increase]. PMID- 26152098 TI - [Quality of care" Alain Berset gives up on part of his project]. PMID- 26152099 TI - [Founding Medicine on values: yes, but which ones?]. PMID- 26152100 TI - An evaluation study of the implementation of stroke best practice guidelines using a Knowledge Transfer Team approach. AB - INTRODUCTION: Strokes will become an increasing burden on the Canadian health care and social systems in coming years. Caring for people who have experienced a stroke is a challenging issue. The Registered Nurses Association of Ontario (RNAO) developed Stroke Assessment Across the Continuum Best Practice Guidelines (BPGs) to support the best possible care for this population. This article reports the findings of an evaluation of the implementation of recommendations from the stroke BPGs using a Knowledge Transfer Team (KTT) at Mackenzie Health's Integrated Stroke Unit in Richmond Hill, Ontario. METHODS: Over a 12-month period, an evaluation of the implementation activities using structure, process, and outcome indicators, as well as identifying effective strategies for system wide dissemination of BPG implementation and outcomes was completed. Data were collected from the staff, KTT members, and patients and their providers. RESULTS: The results clearly illustrate that all of the health care professionals involved in the study felt the KT approach was an effective method of implementing and disseminating the stroke BPGs. The main limitations perceived by staff and KTT members were time constraints, difficulty recruiting a larger sample size, competing priorities, lack of compliance, changes to charting, staff attrition, and a lack of financial support. CONCLUSION: The KTT approach resulted in improved patient care and outcomes, as illustrated by the high patient satisfaction levels. PMID- 26152101 TI - Adjunctive hyperbaric oxygen therapy for diabetic foot ulcers: An editorial perspective. PMID- 26152102 TI - Impact of hyperbaric oxygen on diabetic ulcers is unaffected by glycemic control. AB - Hyperbaric oxygen (HBO2) therapy is an established intervention for treating chronic diabetic lower extremity ulcers, but the impact of glycemic control on its efficacy has not been determined. The purpose of this study was to evaluate the impact of blood glucose control at initiation of HBO2 treatment on wound healing. Hemoglobin A1c (HbA1c) was measured at start of HBO2 therapy for 22 patients undergoing treatment of chronic lower extremity ulcers at two regional wound care centers. Patients with HbA1c < 7.5% were stratified into a "good glycemic control" group (n = 12, mean HbA1c 6.5 +/- 0.8%), and patients with HbA1c >= 7.5% were stratified into a "poor glycemic control" group (n = 10, mean HbA1c 8.8 +/- 1.4%, p = 0.004 compared to "good glycemic control group"). After 20 HBO2 sessions over 30 days in addition to standard wound care interventions, there was no difference in wound healing between the two glycemic control groups as indicated by. reduction from baseline in ulcer surface area, depth, or volume. The diabetic lower extremity wound response to HBO2 therapy is unaffected by glycemic control prior to treatment, and HBO2 treatment should not be delayed for suboptimal blood glucose control. PMID- 26152103 TI - The incidence of hypoglycemia during HBO2 therapy: A retrospective review. AB - BACKGROUND: Hypoglycemia is concerning in patients with diabetes undergoing hyperbaric oxygen (HBO2) therapy. We aimed to estimate the incidence, risk factors and a pretreatment glucose threshold of HBO2-associated hypoglycemia. METHODS: We retrospectively evaluated a patient cohort undergoing HBO2 therapy. We calculated the area under the curve (AUC) and odds ratio (OR) with 95% confidence interval (CI) adjusting for patients' age, gender, diabetes type, insulin use, body mass index, hemoglobin A1c and HBO2 treatment time. RESULTS: During 77 months, 3,136 HBO2 sessions were performed on patients with diabetes. In-chamber glucose was higher than pre-HBO2 glucose in 1,708/3,136 sessions (54%). The incidence of hypoglycemia (defined as <= 70 mg/dL) during or immediately after HBO2 treatment was 1.5% (0.8-2.1%). Hypoglycemia that was symptomatic or severe was rare. A glucose value pre-HBO2 of 150 mg/dL best predicted the risk of subsequent hypoglycemia (AUC 0.80; 95% CI, 0.75-0.86). Type 1 diabetes was independently associated with increased risk of hypoglycemia (OR 3.69; 95% CI, 1.67, 8.19) whereas insulin use was not. CONCLUSIONS: In patients with diabetes undergoing HBO2, severe hypoglycemia is rare and occurs more frequently in Type 1 diabetes. Pre-HBO2 glucose values may be used to predict subsequent hypoglycemia and reduce the need for routine glucose monitoring during and after HBO2. PMID- 26152104 TI - Glycosylated hemoglobin and hyperbaric oxygen coverage denials. AB - Some Medicaid and Medicare fiscal intermediaries are denying hyperbaric oxygen (HBO2) therapy for diabetic foot ulcer (DFU) patients if the glycosylated hemoglobin (HbA1c) > 7.0%. We performed multiple PubMed searches for any diabetic wound healing clinical trial that documented HbA1c and had a wound healing endpoint. We scrutinized 30 peer-reviewed clinical trials, representing more than 4,400 patients. The average HbA1c from the intervention side of the studies was 8.6% (7.2% - 9.9%) and the control/sham side was 8.3% (6.0% - 10.6%). Twelve studies made a direct attempt to link HbA1c and wound healing. Four retrospective studies and one prospective cohort study assert that lower HbA1c favors wound healing, but review of the studies reveal design flaws that invalidate these conclusions. In total, 25 studies showed no direct correlation between HbA1c levels and wound healing. There was no randomized controlled trial (RCT) data demonstrating that HbA1c < 7.0% improves diabetic wound healing. In every study reviewed, wounds healed with high HbA1c levels that would be considered poorly controlled by the American Diabetes Association (ADA). Frequently, patients lack optimal blood glucose control when they have a limb-threatening DFU. The evidence supports that denying hyperbaric oxygen to those with HbA1c > 7.0% is unfounded. PMID- 26152105 TI - A clinical practice guideline for the use of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers. AB - BACKGROUND: The role of hyperbaric oxygen (HBO2) for the treatment of diabetic foot ulcers (DFUs) has been examined in the medical literature for decades. There are more systematic reviews of the HBO2/DFU literature than there have been randomized controlled trials (RCTs), but none of these reviews has resulted in a clinical practice guideline (CPG) that clinicians, patients and policy-makers can use to guide decision-making in everyday practice. METHODS: The Undersea and Hyperbaric Medical Society (UHMS), following the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, undertook this systematic review of the HBO2 literature in order to rate the quality of evidence and generate practice recommendations for the treatment of DFUs. We selected four clinical questions for review regarding the role of HBO2 in the treatment of DFUs and analyzed the literature using patient populations based on Wagner wound classification and age of the wound (i.e., acute post operative wound vs. non-healing wound of 30 or more days). Major amputation and incomplete healing were selected as critical outcomes of interest. RESULTS: This analysis showed that HBO2 is beneficial in preventing amputation and promoting complete healing in patients with Wagner Grade 3 or greater DFUs who have just undergone surgical debridement of the foot as well as in patients with Wagner Grade 3 or greater DFUs that have shown no significant improvement after 30 or more days of treatment. In patients with Wagner Grade 2 or lower DFUs, there was inadequate evidence to justify the use of HBO2 as an adjunctive treatment. CONCLUSIONS: Clinicians, patients, and policy-makers should engage in shared decision-making and consider HBO2 as an adjunctive treatment of DFUs that fit the criteria outlined in this guideline. The current body of evidence provides a moderate level of evidence supporting the use of HBO2 for DFUs. Future research should be directed at improving methods for patient selection, testing various treatment protocols and improving our confidence in the existing estimates. PMID- 26152106 TI - Thermoneutral water immersion and hyperbaric oxygen do not alter cortisol regulation. AB - Research documenting changes in cortisol concentration following hyperbaric exposures has been contradictory, possibly due to the inclusion of many confounding factors. Therefore, the aim of this study was to document short- and long-term cortisol responses following repeated water immersions arid/or exposure to raised partial pressure of oxygen under controlled conditions. Thirty-two Navy divers (31 +/- 7 [19-44] years; mean +/- SD) were exposed to one of three resting thermoneutral experimental conditions at a pressure of 1.35 atmospheres absolute (atm abs) for six hours on five consecutive days: (1) breathing air while immersed (air; n = 10); (2) breathing 100% oxygen in a hyperbaric chamber (dry; n = 12); or (3) breathing 100% oxygen while immersed (oxygen; n = 10). Divers were at rest for all conditions. Serum cortisol concentrations were measured one hour before and after each dive. The change in cortisol (ug/dL) after diving was similar for air (3.63 +/- 5.56), dry (4.91 +/- 3.68) and oxygen (3.50 +/- 3.48) phases (p > 0.05). There were no differences in preor post-dive cortisol concentrations across dive days for any of the experimental conditions. This study provides evidence that repeated long-duration, thermoneutral immersions and/or hyperbaric oxygen exposures at 1.35 atm abs, under ideal conditions per se do not abnormally alter cortisol concentrations. Observed changes are likely the result of the natural circadian rhythm of cortisol. PMID- 26152107 TI - Effect of hyperbaric oxygen conditions on the ordering of interfacial water. AB - Hyperbaric oxygen (HBO2) conditions are applied clinically to treat diverse conditions. There is a lack of a unifying consensus as to how HBO2 acts effectively against a broad range of medical conditions, and numerous differing biological explanations have been offered. The possibility of a mechanism dependent on the extensive ordering of interfacial water has not yet been investigated. We examined the hypothesis that zones of ordered water, dubbed "exclusion zones" or "EZ," are expanded under hyperbaric oxygen conditions. Specifically, we tested whether there are significant quantitative differences in EZ size at steady state under high-pressure and/or high-oxygen conditions, compared to normal atmospheric conditions. Oxygen concentration and mechanical pressure were examined separately and in combination. Statistically significant increases in EZ size were seen at elevated air pressures and at high oxygen concentrations. These experimental results suggest the possibility of an ordered water-mediated mechanism of action for hyperbaric oxygen therapy. PMID- 26152108 TI - The O'Neill grading system for evaluation of the tympanic membrane: A practical approach for clinical hyperbaric patients. AB - Eustachian tube dysfunction (ETD) and middle ear barotrauma (MEB) are the two most common complications of clinical hyperbaric oxygen (HBO2) treatment. The current grading system, the Teed's Classification, was first described in 1944 with modifications to this system over the years, but none are specific for the evaluation and treatment of patients undergoing clinical HBO2 therapy. Currently, the standard of care is a baseline otoscopic examination performed prior to starting HBO2 therapy. Repeat otoscopy is required for patients having ETD, pain or other symptoms during the compression and/or decompression phase of the treatment. Results from these examinations are used to determine the proper course of treatment for the ETD or MEB. The Teed's classification was not intended to correlate with the consistency of diagnosis, the clinical approach to relieving symptoms or the treatment of the inflicted trauma. It is not a practical tool for the modern hyperbaric team. We describe a newer grading system, the O'Neill Grading System (OGS), which allows simple, practical and consistent classification of ETD and MEB by all members of the clinical hyperbaric medicine team. Based on the O'Neill Grade assigned, evidence supported suggestions for appropriate actions and medical interventions are offered. PMID- 26152109 TI - Ambulatory measurement of ambient carbon monoxide levels. AB - BACKGROUND: Measurement of air pollutant levels in the environment is traditionally performed using monitors in fixed locations so that changes over time can be directly compared. Such measurements do not necessarily correlate with the level of exposure to the individual because of distance to the monitoring site and other factors. In the case of carbon monoxide (CO), portable personal monitors are available for industrial use, some of which do not just alarm, but also record measured values. OBJECTIVES: First, it was the purpose of this study to test the feasibility of continuously measuring ambient CO levels in an ambulatory fashion. The second objective was to compare measurements made in a country with significant air pollution to one without to determine the degree to which differences might be observed. METHODS: Ambient CO levels were measured and recorded every 10 minutes during 13 days of travel in Vietnam. A parallel study was performed in the United States for comnarison. RESULTS: Continuous ambient CO levels at an individual level were successfully measured and recorded. Mean ambient CO level throughout Vietnam was 3.5 +/- 4.4 ppm, as compared to 0.9 +/- 0.8 ppm in the U.S. (p < 0.001). In Vietnam, 36 CO measurements (2% of total) were 15 ppm or greater vs. none in the U.S. Higher mean levels, as well as number and magnitude of peaks, were highly associated with proximity to traffic. CONCLUSIONS: Personal exposures to CO can be measured easily over time and may be more relevant to the individual with underlying disease than data from fixed monitoring stations. Such information may prove useful to potential travelers. Additionally, governmental agencies may find ambulatory measurement to be complimentary to data from fixed monitoring stations when attempting to estimate how traditionally collected data relate to exposure of the individual. The technique could also be used for evaluation of vague complaints suggestive of intermittent CO exposure in the home or workplace. PMID- 26152110 TI - Compromised breast flap treated with leech therapy, hyperbaric oxygen, pentoxifylline and topical nitroglycerin: A case report. AB - INTRODUCTION: Hyperbaric oxygen (HBO2) is often indicated in compromised surgical flaps. Although limited to animal models and human case reports, the utilization of leech therapy (Hirudo medicinalis) with HBO2 provides better outcomes than each modality alone. Topical nitroglycerin and pentoxifylline are also frequently used adjunctively for compromised flaps. We present a case of successful breast flap salvage utilizing a combination of leech therapy, HBO2, topical nitroglycerin and pentoxifylline. CASE REPORT: A 34-year-old female, one day post status cosmetic breast reduction mammoplasty developed a dusky discoloration of the left nipple areolar complex, indicating imminent flap failure. The patient was immediately treated with topical nitroglycerin, oral pentoxifylline, and referred for HBO2. After her first HBO2 treatment, there was clinical improvement to the superior portion of the areolar flap, with little improvement inferiorly where the discoloration had remained essentially unchanged. To address this, we added leech therapy and discontinued the topical nitroglycerin. Ceftriaxone for Aeromonas prophylaxis was started, and leeches were attached two at a time and removed from the area once feeding had ceased. These were applied three times per day for three days while receiving HBO2 twice per day for six days. The patient's flap improved and completely healed by Week 8 without need for further surgery. CONCLUSION: This is the first case to our knowledge of successful breast flap salvage using a combination of leech therapy, HBO2, topical nitroglycerin and pentoxifylline. PMID- 26152111 TI - Exploring the utility of cross-laboratory RAD-sequencing datasets for phylogenetic analysis. AB - BACKGROUND: Restriction site-Associated DNA sequencing (RAD-Seq) is widely applied to generate genome-wide sequence and genetic marker datasets. RAD-Seq has been extensively utilised, both at the population level and across species, for example in the construction of phylogenetic trees. However, the consistency of RAD-Seq data generated in different laboratories, and the potential use of cross species orthologous RAD loci in the estimation of genetic relationships, have not been widely investigated. This study describes the use of SbfI RAD-Seq data for the estimation of evolutionary relationships amongst ten teleost fish species, using previously established phylogeny as a benchmark. RESULTS: The number of orthologous SbfI RAD loci identified decreased with increasing evolutionary distance between the species, with several thousand loci conserved across five salmonid species (divergence ~50 MY), and several hundred conserved across the more distantly related teleost species (divergence ~100-360 MY). The majority (>70%) of loci identified between the more distantly related species were genic in origin, suggesting that the bias of SbfI towards genic regions is useful for identifying distant orthologs. Interspecific single nucleotide variants at each orthologous RAD locus were identified. Evolutionary relationships estimated using concatenated sequences of interspecific variants were congruent with previously published phylogenies, even for distantly (divergence up to ~360 MY) related species. CONCLUSION: Overall, this study has demonstrated that orthologous SbfI RAD loci can be identified across closely and distantly related species. This has positive implications for the repeatability of SbfI RAD-Seq and its potential to address research questions beyond the scope of the original studies. Furthermore, the concordance in tree topologies and relationships estimated in this study with published teleost phylogenies suggests that similar meta-datasets could be utilised in the prediction of evolutionary relationships across populations and species with readily available RAD-Seq datasets, but for which relationships remain uncharacterised. PMID- 26152112 TI - Procedure-based severity index for inpatients: development and validation using administrative database. AB - BACKGROUND: Risk adjustment is important in studies using administrative databases. Although utilization of diagnostic and therapeutic procedures can represent patient severity, the usability of procedure records in risk adjustment is not well-documented. Therefore, we aimed to develop and validate a severity index calculable from procedure records. METHODS: Using the Japanese nationwide Diagnosis Procedure Combination database of acute-care hospitals, we identified patients discharged between 1 April 2012 and 31 March 2013 with an admission precipitating diagnosis of acute myocardial infarction, congestive heart failure, acute cerebrovascular disease, gastrointestinal hemorrhage, pneumonia, or septicemia. Subjects were randomly assigned to the derivation cohort or the validation cohort. In the derivation cohort, we used multivariable logistic regression analysis to identify procedures performed on admission day which were significantly associated with in-hospital death, and a point corresponding to regression coefficient was assigned to each procedure. An index was then calculated in the validation cohort as sum of points for performed procedures, and performance of mortality-predicting model using the index and other patient characteristics was evaluated. RESULTS: Of the 539 385 hospitalizations included, 270 054 and 269 331 were assigned to the derivation and validation cohorts, respectively. Nineteen significant procedures were identified from the derivation cohort with points ranging from -3 to 23, producing a severity index with possible range of -13 to 69. In the validation cohort, c-statistic of mortality predicting model was 0.767 (95 % confidence interval: 0.764-0.770). The omega statistic representing contribution of the index relative to other variables was 1.09 (95 % confidence interval: 1.03-1.17). CONCLUSIONS: Procedure-based severity index predicted mortality well, suggesting that procedure records in administrative database are useful for risk adjustment. PMID- 26152114 TI - "Paedatric sepsis six" requires further validation. PMID- 26152113 TI - Comparative microRNA profiling of sporadic and BRCA1 associated basal-like breast cancers. AB - BACKGROUND: While a number of studies have examined miRNA profiles across the molecular subtypes of breast cancer, it is unclear whether BRCA1 basal-like cancers have a specific miRNA profile. This study aims to compare grade independent miRNA expression in luminal cancers, sporadic and BRCA1 basal-type breast cancers. It also aims to ascertain an immunohistochemical profile regulated by BRCA1 specific miRNAs for potential diagnostic use. METHODS: miRNA expression was assessed in 11 BRCA1 basal, 16 sporadic basal, 17 luminal grade 3 cancers via microarrays. The expression of Cyclin D1, FOXP1, FIH-1, pan-ERbeta, NRP1 and CD99, predicted to be regulated by BRCA1 specific miRNAs by computer prediction algorithms, was assessed via immunohistochemistry in a cohort of 35 BRCA1 and 52 sporadic basal-like cancers. Assessment of cyclin D1, FOXP1, NRP1 and CD99 expression was repeated on a validation cohort of 82 BRCA1 and 65 sporadic basal-like breast cancers. RESULTS: Unsupervised clustering of basal cancers resulted in a "sporadic" cluster of 11 cancers, and a "BRCA1" cluster of 16 cancers, including a subgroup composed entirely of 10 BRCA1 cancers. Compared with sporadic basal cancers, BRCA1 cancers showed reduced positivity for proteins predicted to be regulated by miRNAs: FOXP1 (6/20[30 %] vs. 37/49[76 %], p < 0.001), cyclin D1 (8/22[36 %] vs. 30/46[65 %], p = 0.025), NRP1 (2/20[10 %] vs. 23/46[50 %], p = 0.002). This was confirmed in the validation cohort (all p < 0.001). Negative staining for 2 or more out of FOXP1, cyclin D1 and NRP1 predicts germline BRCA1 mutation with a sensitivity of 92 %, specificity of 44 %, positive predictive value of 38 % and a negative predictive value of 94 %. CONCLUSION: Sporadic and BRCA1 basal-like cancers have grade independent miRNA expression profiles. Furthermore miRNA driven differences in the expression of proteins in BRCA1 basal cancers may be detected via immunohistochemistry. These findings may have important diagnostic implications, as immunohistochemical assessment of basal cancers, in addition to the patient's family and clinical history, may potentially identify patients who may benefit from BRCA1 gene testing. PMID- 26152115 TI - In-vitro degradation characteristics of poly(e-caprolactone)/poly(glycolic acid) scaffolds fabricated via solid-state cryomilling. AB - Poly(e-caprolactone) (PCL)/poly(glycolic acid) (PGA) scaffolds were fabricated via solid-state cryomilling along with compression molding and porogen leaching techniques. Four types of scaffolds were produced using four distinct cryomilling times. These scaffolds were evaluated for their in-vitro degradation behavior hydrolytically in phosphate buffer saline (PBS). The degradation profiles were investigated over a period of 60 days. The percentage of weight loss, percentage of water absorption, morphology, compressive, thermal, and material properties were studied as a function of degradation time. Weight loss and water absorption demonstrated a high correlation, which showed an increasing behavior with increase in cryomilling time and degradation time. Morphology of the scaffolds analyzed through scanning electron microscopy (SEM) revealed micro-cracks on the surface of the cylindrical struts due to hydrolytic attack and dissolution of hydrophilic PGA. Changes in compressive modulus and crystallinity over the degradation period and material properties were analyzed using X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. DSC and XRD results indicated that hydrolytic attack had taken place during degradation, resulting in moments of increased and decreased percent crystallinity. This study successfully brought forth the differences in resultant properties of the PCL/PGA scaffolds as a function of degradation time. PMID- 26152117 TI - Weekend hospital death rates are not just an English problem. PMID- 26152116 TI - Surgical and interventional management of mitral valve regurgitation: a position statement from the European Society of Cardiology Working Groups on Cardiovascular Surgery and Valvular Heart Disease. PMID- 26152118 TI - Readiness for health behavior changes among low fitness men in a Finnish health promotion campaign. AB - Men have been a hard-to-reach population in health behavior programs and it has been claimed that they are less interested in health issues than women. However, less is known about that how ready men are to adopt new health behaviors. This study examined readiness for change in physical activity (PA) and eating behavior (EB) among low fitness and overweight working-aged Finnish men who participated in a PA campaign. Associations among perceived health knowledge, health behaviors, psychosocial factors and readiness for change were studied. Data comprised 362 men aged 18-64. Physical fitness was assessed with a body fitness index constructed on the basis of the Polar OwnIndex Test, a hand grip test and an Inbody 720 body composition analysis. Health behavior information was gathered by questionnaire. Descriptive and comparative analyses were conducted by chi2 test and Kruskall-Wallis and Mann-Whitney U tests. Associations between health knowledge and health behaviors were explored with logistic regression analyses. Readiness to increase PA and change EB was positively related to higher scores in psychosocial factors, PA and healthy eating habits. Self-rated knowledge on health issues was not related to PA or readiness to change health behaviors; however, it was positively associated with healthy eating and greater perceived promoters of PA. Participants' self-rated knowledge reflected not only an interest in health but also the differences in age and education. Health programs are needed that target both PA and healthy eating in low-fit men at different ages and motivational stages. PMID- 26152120 TI - Acrokeratosis paraneoplastica in serous ovarian carcinoma: case report. AB - BACKGROUND: Acrokeratosis paraneoplastica is a rare paraneoplastic phenomenon associated with upper aerodigestive tract carcinomas, usually manifesting as psoriasiform keratosis over the acral sites. It is primarily seen in white males above the age of 40 years. Here we report a case of paraneoplastic acrokeratosis in a woman with serous ovarian cancer. To the best of our knowledge, no similar case has been reported previously. CASE PRESENTATION: We report the case of a 60 year-old woman diagnosed with a serous ovarian cancer and complaining of a thickening and peeling of the skin on her feet. Clinical and histological examination, as well as the course of disease, confirmed the diagnosis of a paraneoplastic plantar keratosis. Under systemic chemotherapy with carboplatin and paclitaxel the lesion resolved gradually in concordance with tumour marker CA 125. CONCLUSIONS: We present the reported case of paraneoplastic acrokeratosis associated with advanced high-grade ovarian cancer. PMID- 26152119 TI - Estrogen induces two distinct cholesterol crystallization pathways by activating ERalpha and GPR30 in female mice. AB - To distinguish the lithogenic effect of the classical estrogen receptor alpha (ERalpha) from that of the G protein-coupled receptor 30 (GPR30), a new estrogen receptor, on estrogen-induced gallstones, we investigated the entire spectrum of cholesterol crystallization pathways and sequences during the early stage of gallstone formation in gallbladder bile of ovariectomized female wild-type, GPR30((-/-)), ERalpha((-/-)), and GPR30((-/-))/ERalpha((-/-)) mice treated with 17beta-estradiol (E2) at 6 ug/day and fed a lithogenic diet for 12 days. E2 disrupted biliary cholesterol and bile salt metabolism through ERalpha and GPR30, leading to supersaturated bile and predisposing to the precipitation of cholesterol monohydrate crystals. In GPR30((-/-)) mice, arc-like and tubular crystals formed first, followed by classical parallelogram-shaped cholesterol monohydrate crystals. In ERalpha((-/-)) mice, precipitation of lamellar liquid crystals, typified by birefringent multilamellar vesicles, appeared earlier than cholesterol monohydrate crystals. Both crystallization pathways were accelerated in wild-type mice with the activation of GPR30 and ERalpha by E2. However, cholesterol crystallization was drastically retarded in GPR30((-/-))/ERalpha((-/ )) mice. We concluded that E2 activates GPR30 and ERalpha to produce liquid crystalline versus anhydrous crystalline metastable intermediates evolving to cholesterol monohydrate crystals from supersaturated bile. GPR30 produces a synergistic lithogenic action with ERalpha to enhance E2-induced gallstone formation. PMID- 26152121 TI - Spinal intradural metastasis from scapular Ewing sarcoma. AB - BACKGROUND: Ewing sarcoma is a primary bone neoplasm, which is a high grade aggressive small round blue cell tumour, and is currently recognized as a part of the Ewing family of tumours. It is the most lethal bone tumor, and is a rare malignant bone tumor accounting for 10% of all primary bone tumors, and 6% of malignant bone tumors. It has an average annual incidence of 3 per 1 million, found almost exclusively in Caucasians. It commonly occurs in long bones and pelvis but rarely involves the scapula. 85% of cases have metastasis within 2 years of diagnosis, rarely involving the meninges. CASE PRESENTATION: We report a case of a 25 year old Sinhalese Sri Lankan female, presenting with a 1 day history of bilateral lower limb weakness and urinary incontinence. She had a sensory level with flaccid paralysis of lower limbs and a painless bony lump in the left dorsal scapula. Investigations showed scapular primary Ewing sarcoma giving rise to spinal intradural metastasis. For the best of our knowledge this is the first reported case of a scapular Ewing sarcoma with spinal intradural metastasis presenting with lower limb paralysis. CONCLUSION: Intradural spinal metastasis of Ewing sarcoma presenting with lower limb weakness, without a history of pain, though rarely, can be the first presentation, and can rapidly progress to brainstem involvement and death. PMID- 26152122 TI - Balancing costs and benefits at different stages of medical innovation: a systematic review of Multi-criteria decision analysis (MCDA). AB - BACKGROUND: The diffusion of health technologies from translational research to reimbursement depends on several factors included the results of health economic analysis. Recent research identified several flaws in health economic concepts. Additionally, the heterogeneous viewpoints of participating stakeholders are rarely systematically addressed in current decision-making. Multi-criteria Decision Analysis (MCDA) provides an opportunity to tackle these issues. The objective of this study was to review applications of MCDA methods in decisions addressing the trade-off between costs and benefits. METHODS: Using basic steps of the PRISMA guidelines, a systematic review of the healthcare literature was performed to identify original research articles from January 1990 to April 2014. Medline, PubMed, Springer Link and specific journals were searched. Using predefined categories, bibliographic records were systematically extracted regarding the type of policy applications, MCDA methodology, criteria used and their definitions. RESULTS: 22 studies were included in the analysis. 15 studies (68 %) used direct MCDA approaches and seven studies (32 %) used preference elicitation approaches. Four studies (19 %) focused on technologies in the early innovation process. The majority (18 studies - 81 %) examined reimbursement decisions. Decision criteria used in studies were obtained from the literature research and context-specific studies, expert opinions, and group discussions. The number of criteria ranged between three up to 15. The most frequently used criteria were health outcomes (73 %), disease impact (59 %), and implementation of the intervention (40 %). Economic criteria included cost-effectiveness criteria (14 studies, 64 %), and total costs/budget impact of an intervention (eight studies, 36 %). The process of including economic aspects is very different among studies. Some studies directly compare costs with other criteria while some include economic consideration in a second step. CONCLUSIONS: In early innovation processes, MCDA can provide information about stakeholder preferences as well as evidence needs in further development. However, only a minority of these studies include economic features due to the limited evidence. The most important economic criterion cost-effectiveness should not be included from a technical perspective as it is already a composite of costs and benefit. There is a significant lack of consensus in methodology employed by the various studies which highlights the need for guidance on application of MCDA at specific phases of an innovation. PMID- 26152123 TI - Effect of outdoor activity on myopia onset and progression in school-aged children in northeast China: the Sujiatun Eye Care Study. AB - BACKGROUND: Due to its high prevalence and associated sight-threatening pathologies, myopia has emerged as a major health issue in East Asia. The purpose was to test the impact on myopia development of a school-based intervention program aimed at increasing the time student spent outdoors. METHODS: A total of 3051 students of two primary (grades 1-5, aged 6-11) and two junior high schools (grades 7-8, aged 12-14) in both urban and rural Northeast China were enrolled. The intervention group (n = 1735) unlike the control group (n = 1316) was allowed two additional 20-min recess programs outside the classroom. A detailed questionnaire was administered to parents and children. Uncorrected visual acuity (UCVA) was measured using an E Standard Logarithm Vision Acuity Chart (GB11533 2011) at baseline, 6-month and 1-year intervals. A random subsample (n = 391) participated in the clinic visits and underwent cycloplegia at the beginning and after 1 year. RESULTS: The mean UCVA for the entire intervention group was significantly better than the entire control group after 1 year (P < 0.001). In the subgroup study, new onset of myopia and changes in refractive error towards myopia were direction during the study period was significantly lower in the intervention group than in the control group (3.70 % vs. 8.50 %, P = 0.048; -0.10 +/- 0.65 D/year vs. -0.27 +/- 0.52 D/year, P = 0.005). Changes in axial length and IOP were also significantly lower following the intervention group (0.16 +/- 0.30 mm/year vs. 0.21 +/- 0.21 mm/year, P = 0.034; -0.05 +/- 2.78 mmHg/year vs. 0.67 +/- 2.21 mmHg/year, P = 0.006). CONCLUSIONS: Increasing outdoor activities prevented myopia onset and development, as well as axial growth and elevated IOP in children. TRIAL REGISTRATION: Current controlled trials NCT02271373. PMID- 26152124 TI - Budget impact assessment of Aprokam(r) compared with unlicensed cefuroxime for prophylaxis of post-cataract surgery endophthalmitis. AB - BACKGROUND: Intracameral cefuroxime is recommended as prophylaxis against postoperative endophthalmitis (POE) following cataract surgery. Aprokam is the only licensed product for prophylaxis of POE, although unlicensed intracameral cefuroxime may be administered using pre-filled syringes (PFS), either prepared in hospital by reconstituting cefuroxime via serial dilution (prepared PFS), or commercially purchased (purchased PFS). This study aimed to estimate the potential budget impact of using Aprokam over unlicensed cefuroxime for intracameral administration. METHODS: A budget impact model (BIM) was developed from UK NHS hospital perspective to estimate the economic impact of adopting Aprokam compared with purchased PFS or prepared PFS for the prophylaxis of POE following cataract surgery over a 5-year time horizon. The BIM incorporated direct costs only, associated with the acquisition, delivery, storage, preparation, and administration of cefuroxime. Resource utilisation costs were also incorporated; resource utilisation was sourced from a panel survey of hospital pharmacists, surgeons, and theatre nurses who are involved in the delivery, storage, preparation, quality assurance, or administration of cefuroxime formulations. Unit costs were sourced from NHS sources; drug acquisition costs were sourced from BNF. The model base case used a hypothetical cohort comprising of 1000 surgeries in the first year and followed a 5.2 % annual increase each year. RESULTS: The model predicts Aprokam is cost saving compared with purchased PFS, with a modest increase compared prepared PFS over 5 years. There are total savings of L 3490 with Aprokam compared with purchased PFS, driven by savings in staff costs that offset greater drug acquisition costs. Compared with prepared PFS, there are greater drug acquisition costs which drive an increased total cost over 5 years of L 13,177 with Aprokam, although there are substantial savings in staff costs as well as consumables and equipment costs. CONCLUSIONS: The lower direct costs of using Aprokam compared with purchased PFS presents a strong argument for the adoption of Aprokam where purchased PFS is administered. The additional benefits of Aprokam include increased liability coverage and possible reduction in dilution errors and contaminations; as such, in hospitals where unlicensed prepared PFS is used, modest additional resources should be allocated to adoption of Aprokam. PMID- 26152125 TI - IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Circadian Period of PER2 Expression in the Suprachiasmatic Nucleus. AB - Neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals, display daily rhythms in electrical activity with more depolarized resting potentials and higher firing rates during the day than at night. Although these daily variations in the electrical properties of SCN neurons are required for circadian rhythms in physiology and behavior, the mechanisms linking changes in neuronal excitability to the molecular clock are not known. Recently, we reported that mice deficient for either Kcna4 (Kv1.4(-/-)) or Kcnd2 (Kv4.2(-/-); but not Kcnd3, Kv4.3(-/-)), voltage-gated K(+) (Kv) channel pore-forming subunits that encode subthreshold, rapidly activating, and inactivating K(+) currents (IA), have shortened (0.5 h) circadian periods in SCN firing and in locomotor activity compared with wild-type (WT) mice. In the experiments here, we used a mouse (Per2(Luc)) line engineered with a bioluminescent reporter construct, PERIOD2::LUCIFERASE (PER2::LUC), replacing the endogenous Per2 locus, to test the hypothesis that the loss of Kv1.4- or Kv4.2-encoded IA channels also modifies circadian rhythms in the expression of the clock protein PERIOD2 (PER2). We found that SCN explants from Kv1.4(-/-)Per2(Luc) and Kv4.2(-/-) Per2(Luc), but not Kv4.3(-/-)Per2(Luc), mice have significantly shorter (by approximately 0.5 h) circadian periods in PER2 rhythms, compared with explants from Per2(Luc) mice, revealing that the membrane properties of SCN neurons feedback to regulate clock (PER2) expression. The combined loss of both Kv1.4- and Kv4.2-encoded IA channels in Kv1.4(-/-)/Kv4.2(-/-)Per2(Luc) SCN explants did not result in any further alterations in PER2 rhythms. Interestingly, however, mice lacking both Kv1.4 and Kv4.2 show a striking (approximately 1.8 h) advance in their daily activity onset in a light cycle compared with WT mice, suggesting additional roles for Kv1.4- and Kv4.2-encoded IA channels in controlling the light-dependent responses of neurons within and/or outside of the SCN to regulate circadian phase of daily activity. PMID- 26152127 TI - Vitamin D therapy in chronic kidney disease: back to the future? AB - Deficiency of 1,25(OH)2 vitamin D is inevitable in CKD, and is part of a cascade of bone and mineral abnormalities that result in secondary hyperparathyroidism. The widespread acceptance of calcitriol therapy as the treatment paradigm, has resulted in an overall neglect of vitamin D deficiency, as defined by low serum 25(OH)D levels Recent research has greatly enhanced our understanding of the disordered vitamin D metabolism seen in CKD. Furthermore vitamin D has been implicated in numerous disease states, beyond its traditional role in regulating bone and mineral metabolism. Low serum 25(OH)D levels have been linked to numerous adverse clinical outcomes in health and CKD. Additionally, the recognition of extra-renal, autocrine 1,25(OH)2D synthesis, present in many tissues, has refocused attention on the therapeutic potential of correcting low serum 25(OH)D levels. In this review we examine the physiology of disordered vitamin D metabolism in CKD, the clinical associations of low 25(OH)D levels in CKD, and discuss the rationale for vitamin D replacement in current clinical practice. PMID- 26152128 TI - Markers of Individual Drug Metabolism: Towards the Development of a Personalized Antidepressant Prescription. AB - The development of a personalized psychopharmacotherapy could potentially reduce treatment failure associated with drug intolerance or resistance, and therefore the burden and costs of affective disorders. An important challenge in realising this potential will be to identify suitable markers of an individual's metabolic response to specific pharmaceuticals. In the absence of suitable markers related directly to drug mechanism, the drug-metabolizing enzymes and transporters have emerged as major determinants of variability in drug metabolism and response. In keeping with this emergent general pharmacological trend, numerous studies concerning the relationship between antidepressants, their metabolism, transport, pharmacokinetic properties, efficacy and tolerability have now been published. These studies are reviewed in this article. The studies considered here frequently support a link between enzyme/transporter activity and/or the pharmacokinetic parameters of antidepressants. However, the majority of studies explored the variability of tricyclic antidepressants, which are less often prescribed today. Furthermore only a few studies have been conducted in naturalistic clinical conditions, seeking to determine whether the systematic assessment of the variability may improve the management of 'real-world' patients. Nonetheless recent studies have yielded promising results regarding the potential benefits of determining drug metabolism variability which might encourage additional large-scale prospective systematic studies be set up to assess the relevance of this approach in everyday practice. PMID- 26152129 TI - Systemic Redox Biomarkers in Neurodegenerative Diseases. AB - Neurodegenerative diseases are characterized by a gradual and selective loss of neurons. ROS overload has been proved to occur early in this heterogeneous group of disorders, indicating oxidative stress as a primer factor underlying their pathogenesis. Given the importance of a better knowledge of the cause/effect of oxidative stress in the pathogenesis and evolution of neurodegeneration, recent efforts have been focused on the identification and determination of stable markers that may reflect systemic oxidative stress. This review provides an overview of these systemic redox biomarkers and their responsiveness to antioxidant therapies. Redox biomarkers can be classified as molecules that are modified by interactions with ROS in the microenvironment and antioxidant molecules that change in response to increased oxidative stress. DNA, lipids (including phospholipids), proteins and carbohydrates are examples of molecules that can be modified by excessive ROS in vivo. Some modifications have direct effects on molecule functions (e.g. to inhibit enzyme function), but others merely reflect the degree of oxidative stress in the local environment. Testing of redox biomarkers in neurodegenerative diseases has 3 important goals: 1) to confirm the presence or absence of systemic oxidative stress; 2) to identify possible underlying (and potentially reversible) causes of neurodegeneration; and 3) to estimate the severity of the disease and the risk of progression. Reflecting pathological processes occurring in the whole body, redox biomarkers may pinpoint novel therapeutic targets and lead to diagnose diseases before they are clinically evident. PMID- 26152126 TI - Proteome from patients with metabolic syndrome is regulated by quantity and quality of dietary lipids. AB - BACKGROUND: Metabolic syndrome is a multi-component disorder associated to a high risk of cardiovascular disease. Its etiology is the result of a complex interaction between genetic and environmental factors, including dietary habits. We aimed to identify the target proteins modulated by the long-term consumption of four diets differing in the quality and quantity of lipids in the whole proteome of peripheral blood mononuclear cells (PBMC). RESULTS: A randomized, controlled trial conducted within the LIPGENE study assigned 24 MetS patients for 12 weeks each to 1 of 4 diets: a) high-saturated fatty acid (HSFA), b) high monounsaturated fatty acid (HMUFA), c) low-fat, high-complex carbohydrate diets supplemented with placebo (LFHCC) and d) low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (LFHCC n 3). We analyzed the changes induced in the proteome of both nuclear and cytoplasmic fractions of PBMC using 2-D proteomic analysis. Sixty-seven proteins were differentially expressed after the long-term consumption of the four diets. The HSFA diet induced the expression of proteins responding to oxidative stress, degradation of ubiquitinated proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory and oxidative stress-related proteins and DNA repairing proteins. CONCLUSION: The long-term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, seems to increase the cardiovascular disease (CVD) risk factors associated with metabolic syndrome, such as inflammation and oxidative stress, and seem lead to DNA damage as a consequence of high oxidative stress. PMID- 26152130 TI - Pharmacokinetics and safety of 3,4-diaminopyridine base in healthy Japanese volunteers. AB - OBJECTIVE: 3,4-diaminopyridine (3,4-DAP) is commonly used for treating neuromuscular diseases, such as the Lambert-Eaton myasthenic syndrome, but the pharmacokinetics of 3,4-DAP base have not been investigated. We therefore studied 3,4-DAP base pharmacokinetics in healthy Japanese volunteers. MATERIALS AND METHODS: In this crossover study, we administered a single oral dose of 10 or 20 mg 3,4-DAP base to healthy Japanese volunteers (n = 5) after food intake, or 10 mg 3,4-DAP to fasting individuals. We measured serum 3,4-DAP concentrations, performed electrocardiography (ECG), and administered questionnaires. RESULTS: After administration of 10 or 20 mg 3,4-DAP following food intake, the maximum serum concentrations (Cmax) were 8.09 +/- 4.47 ng/mL and 35.8 +/- 15.7 ng/mL, respectively (mean +/- standard deviation; SD), and the areas under the serum concentration-time curve (extrapolated to infinity) were 639 +/- 213 ng x min/mL and 2,097 +/- 936 ng x min/mL (mean +/- SD), respectively. Administration to fasted individuals indicated that food intake did not significantly alter 3,4-DAP pharmacokinetics. ECG showed no clinically significant changes, but PR intervals were prolonged in all cases. Two out of 5 subjects showed perioral paresthesia symptoms after administration of 20 mg 3,4-DAP. CONCLUSION: This study indicated that 3,4-DAP base pharmacokinetics were non-linear. Although no clinically significant changes in ECG were observed, it is advisable to perform ECG periodically during 3,4-DAP administration in order to monitor cardiac function. Moreover, the development of perioral paresthesia may be dependent on the dose of 3,4-DAP used. PMID- 26152131 TI - Evaluation of the pharmacokinetics and safety of single and multiple ceftaroline fosamil infusions in healthy Chinese and Western subjects. AB - OBJECTIVES: Two phase I studies in healthy Chinese (NCT01458743) and Western (NCT01612507) subjects evaluated the pharmacokinetics (PK) and safety of single and multiple ceftaroline fosamil 600 mg infusions administered every 8 or 12 hours (q8h or q12h). METHODS: Each study enrolled subjects sequentially into 1 of 2 cohorts (cohort 1: 60-minute infusions; cohort 2: 120-minute infusions). All subjects in the Chinese (n = 26) study received open label ceftaroline fosamil; in the Western study, subjects (n = 41) in each cohort were randomized 3 : 1 to ceftaroline fosamil or placebo infusions. Single infusions were administered on days 1 and 8. On days 2 - 7 (3 - 7 for Chinese study, cohort 1) subjects received q12h or q8h infusions. Plasma and urine were collected on days 1 and 8 for PK analysis. RESULTS: Ceftaroline PK was linear and time-independent following single and multiple doses of ceftaroline fosamil. The magnitude and timing of peak plasma concentrations of ceftaroline (active metabolite), ceftaroline fosamil (prodrug), and ceftaroline M-1 (inactive metabolite) varied according to the ceftaroline fosamil dosing schedule (q12h or q8h) and infusion duration (60 minutes or 120 minutes), but overall plasma ceftaroline exposures within the respective dosing intervals were broadly similar across cohorts. The most frequent adverse events were rash/drug eruption, most of which were of mild moderate intensity and considered related to treatment. CONCLUSIONS: Ceftaroline PK was broadly similar in healthy Chinese and Western subjects receiving equivalent dose regimens. The tolerability profile of ceftaroline fosamil in Chinese and Western subjects was consistent with previous clinical trials. PMID- 26152132 TI - Bioequivalence of different dose-strength tablets of selexipag, a selective prostacyclin receptor agonist, in a multiple-dose up-titration study. AB - OBJECTIVE: Selexipag is a novel, oral, selective prostacyclin (PGI2) receptor agonist in clinical development for the treatment of pulmonary arterial hypertension. Film-coated tablets with strength between 200 and 1,600 MUg were used. Bioequivalence between 8 x 200 MUg and a new 1,600 MUg tablet was evaluated at steady state in healthy male subjects. MATERIALS AND METHODS: This was an open label, 2-treatment, 2-period, crossover, up-titration, phase 1 study. The treatments were selexipag at 1,600 MUg b.i.d. for 4.5 days either as 8 x 200 MUg tablets (reference: A) or 1 x 1,600 MUg tablet (test: B), both preceded by an up titration phase starting from 400 MUg b.i.d. doses, in 200-MUg steps every 4th day. Subjects were randomized 1 : 1 to the A-B or B-A sequence. The pharmacokinetics and tolerability of selexipag and its active metabolite, ACT 333679, were investigated. RESULTS: 80 subjects were enrolled in the study: 65 subjects completed the study according to protocol, and 15 subjects withdrew from the study. The most frequent adverse events (AEs) were headache (86%), myalgia (73%), and jaw pain (73%). There was no difference in nature and overall frequency of AEs between the two treatments. Steady state was attained within 3 days of the selexipag 1,600 I1/4g b.i.d. TREATMENTS: The 90% confidence intervals (CIs) of the geometric mean ratio (B/A) at steady state for AUCI? and Cmax,ss were within (0.80, 1.25) bioequivalence interval: (0.92, 1.06) and (0.95, 1.14), respectively, for selexipag and (0.95, 1.06) and (0.94, 1.07), respectively, for the active metabolite, ACT-333679. CONCLUSIONS: Bioequivalence was demonstrated between 8 x 200 MUg and 1 x 1,600 MUg selexipag at steady state. PMID- 26152133 TI - Correlation of Urine Biomarkers: Microalbuminuria and Spot Urine Protein among Diabetic Patients. Application of Spot Urine Protein in Diabetic Kidney Disease, Nephropathy, Proteinuria Estimation, Diagnosing and Monitoring. AB - Current study has invented a new method for utilizing spot urine protein among diabetic patients. There have been various efforts and strategies in research internationally to detect, diagnose and monitor nephropathy/DKD. Although 24-hour urine studies are gold standard, however, there exist some controversies about microalbuminuria and spot urine protein. The current study was designed to utilize spot urine protein among diabetic patients and to find its association with routine dipstick urine test for albumin, and microalbuminuria. The study demonstrated significant association of spot urine protein with urine dipstick albumin, and has demonstrated increasing spot urine protein with increasing albumin in urine (p-value < 0.0001). This study also demonstrated significantly higher levels of spot urine protein between the groups with nephropathy/DKD as compared to those without nephropathy/DKD (p-value < 0.0001). Similarly, spot urine protein and spot urine protein/creatinine were also significantly associated with microalbumin and microalbumin/creatinine in urine. Significant regression models for spot urine protein and microalbuminuria were also developed and proposed to detect and estimate microalbumin in urine while utilizing spot urine protein (< 0.0001). Synthesized regression equations and models can be used confidently to detect, rule out and monitor proteinuria and DKD. ROC curves were utilized to detect spot urine protein cutoff points for nephropathy and DKD with high specificity and sensitivity. Some important patents were also discussed in the paper regarding albuminuria/proteinuria detection and management. Current study has demonstrated and concluded, for the first time, that there exists a significant association of spot urine protein with routine dipstick albumin in urine and microalbuminuria. It is also essential to detect early, monitor and manage proteinuria, hypertension and dyslipidemia with good glycemic control to prevent diabetes complications. PMID- 26152134 TI - Parent distress reactions following a serious illness or injury in their child: a protocol paper for the take a Breath Cohort Study. AB - BACKGROUND: Diagnosis of life threatening childhood illness or injury can lead to significant distress reactions in parents, with many experiencing clinically significant levels of post-traumatic stress symptoms. These symptoms can have long-term adverse impacts on parent mental health, family functioning, and the adjustment of the ill child. Independent studies have found such reactions in several different illness groups. However, very little research has systematically compared the prevalence, impact and trajectories over time of post traumatic stress symptoms in parents across different childhood illness groups with an acute life threat. The current study seeks to map the course of post traumatic stress reactions in parents of children with various life threatening illnesses over an 18 month period, and identify factors that predict successful adaptation in families. METHOD/DESIGN: The current study described is of a prospective, longitudinal design. The sample included parents of children admitted to four major hospital departments at the Royal Children's Hospital, Melbourne, Australia, for a life threatening illness or injury. Eligible parents were those who were caregivers of children aged 0-to 18-years admitted to the Oncology, Cardiology, Neurology and Pediatric Intensive Care Unit. Parents were recruited acutely, and completed self-report questionnaires at four time-points: within the first 4 weeks (T1:); then at 4 months (T2); 7 months (T3); and 19 months (T4) after admission. Questionnaires assessed parent and child mental health and wellbeing, and a number of risk and reliance factors such child illness factors, parent demographic factors, and psychosocial factors. DISCUSSION: This study is one of the first to document the trajectory of post traumatic stress responses in parents of very ill children, across illness groups. Given that it will also identify risk and resilience factors, and map the course of parent outcomes over an 18 monthperiod, it has the potential to inform novel strategies for intervention. PMID- 26152135 TI - Group mindfulness based cognitive therapy vs group support for self-injury among young people: study protocol for a randomised controlled trial. AB - BACKGROUND: Non-suicidal self-injury (NSSI) is a transdiagnostic behaviour that can be difficult to treat; to date no evidence based treatment for NSSI exists. Mindfulness Based Cognitive Therapy (MBCT) specifically targets the mechanisms thought to initiate and maintain NSSI, and thus appears a viable treatment option. The aims of the current study are to test the ability of MBCT to reduce the frequency and medical severity of NSSI, and explore the mechanisms by which MBCT exerts its effect. METHODS/DESIGN: We will conduct a parallel group randomised controlled trial of Mindfulness Based Cognitive Therapy (MBCT) versus Supportive Therapy (ST) in young people aged 18-25 years. Computerised block randomisation will be used to allocate participants to groups. All participants will meet the proposed DSM-5 criteria for NSSI (i.e. five episodes in the last twelve months). Participants will be excluded if they: 1) are currently receiving psychological treatment, 2) have attempted suicide in the previous 12 months, 3) exhibit acute psychosis, 4) have a diagnosis of borderline personality disorder, or 5) have prior experience of MBCT. Our primary outcome is the frequency and medical severity of NSSI. As secondary outcomes we will assess changes in rumination, mindfulness, emotion regulation, distress tolerance, stress, and attentional bias, and test these as mechanisms of change. DISCUSSION: This is the first randomised controlled trial to test the efficacy of MBCT in reducing NSSI. Evidence of the efficacy of MBCT for self-injury will allow provision of a brief intervention for self-injury that can be implemented as a stand-alone treatment or integrated with existing treatments for psychiatric disorders. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number ACTRN12615000023550 . Registered 16 January 2015. PMID- 26152136 TI - Antioxidants and its Properties as Affected by Extrusion Process: A Review. AB - Antioxidants are important for plant and animal's life or health. These are the substances that protect them from the damage produced by unstable molecules called as free radicals. There are various types of antioxidants to be reported both natural as well as synthetic such as melatonin, Vitamin C, glutathione, tocopherols and tocotrienols, BHA and BHT, etc. A new antioxidant 5-O-[6"-(3- hydroxy-3methyl glutarate) beta-D-glucodise was found while studying bioactive antioxidants from plant foods for nutraceutical product development. Antioxidants have been used for increasing shelf life of various food products including extruded product. Antioxidants, their beneficial advantages and the effect of extrusion on antioxidants were reviewed and found to be effective in increasing the shelf life. This review article discusses recent patents, presents importance of antioxidant, phytochemicals and effect of process of extrusion on antioxidants. PMID- 26152137 TI - The problem with eliminating 'low-value care'. PMID- 26152138 TI - Parental attitudes towards male human papillomavirus vaccination: a pan-European cross-sectional survey. AB - BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted virus that can lead to severe diseases in both women and men. Today, HPV vaccination is offered to females only across Europe. We aimed to examine parental attitudes to HPV vaccination of their sons given brief information about HPV in both genders. METHODS: A literature study on acceptability of male HPV vaccination was carried out to inform the construction of a study questionnaire. Following up on a Danish study from 2012, this questionnaire was applied in 1837 computer assisted interviews with parents of sons in the UK, Germany, France and Italy. In each country, the parents were representative in terms of geographical dispersion, city size and age of sons in the household. The applied questionnaires took the varying vaccination policies and delivery systems into account. The data were analysed pooled and for each country using significant statistical tests (chi-2) with a 95 % confidence interval. RESULTS: Approximately 3/4 of parents in the UK, Germany and Italy were in favour of HPV vaccination of their sons. In France, this applied to 49 % of respondents. Favourable parents wanted to protect their sons from disease and found gender equality important. Parents in doubt about male HPV vaccination needed more information about HPV diseases in men and male HPV vaccination; Rejecting parents were generally sceptical of vaccines and feared vaccination side-effects. Parents in countries with active vaccination policies (UK and Italy) tended to trust the importance of national vaccination programmes. Parents in countries with passive vaccination strategies (Germany and France) had greater need for information from health care professionals (HCP) and public health authorities. CONCLUSION: Given brief information about HPV in both genders, parental acceptance of HPV vaccination of sons is as high as acceptance levels for girls. All parents should be informed about HPV to make informed decisions about HPV vaccination for their children. There is a need for joint efforts from public health authorities and HCPs to provide parents with such information. PMID- 26152140 TI - Mammography detects more small cancers but results in overdiagnosis, researchers warn. PMID- 26152139 TI - Meso level influences on long term condition self-management: stakeholder accounts of commonalities and differences across six European countries. AB - BACKGROUND: European countries are increasingly adopting systems of self -care support (SMS) for long term conditions which focus on enhancing individual, competencies, skills, behaviour and lifestyle changes. To date the focus of policy for engendering greater self- management in the population has been focused in the main on the actions and motivations of individuals. Less attention has been paid to how the broader influences relevant to SMS policy and practice such as those related to food production, distribution and consumption and the structural aspects and economics relating to physical exercise and governance of health care delivery systems might be implicated in the populations ability to self- manage. This study aimed to identify key informants operating with knowledge of both policy and practice related to SMS in order to explore how these influences are seen to impact on the self-management support environment for diabetes type 2. METHODS: Ninety semi-structured interviews were conducted with key stakeholder informants in Bulgaria, Spain, Greece, Norway, Netherlands and UK. Interviews were transcribed and analysed using thematic and textual analysis. RESULTS: Stakeholders in the six countries identified a range of influences which shaped diabetes self-management (SM). The infrastructure and culture for supporting self- management practice is viewed as driven by political decision-makers, the socio-economic and policy environment, and the ethos and delivery of chronic illness management in formal health care systems. Three key themes emerged during the analysis of data. These were 1) social environmental influences on diabetes self-management 2) reluctance or inability of policy makers to regulate processes and environments related to chronic illness management 3) the focus of healthcare system governance and gaps in provision of self-management support (SMS). Nuances in the salience and content of these themes between partner countries related to the presence and articulation of dedicated prevention and self- management policies, behavioural interventions in primary care, drug company involvement and the impact of measures resulting from economic crises, and differences between countries with higher versus lower social welfare support and public spending on shaping illness management. CONCLUSIONS: The results suggest reasons for giving increasing prominence to meso level influences as a means of rebalancing and improving the effectiveness of implementing an agenda for SMS. There is a need to acknowledge the greater economic and policy challenging environment operating in some countries which act as a source of inequality between countries in addressing SMS for chronic illness management and impacts on people's capacity to undertake self-care activities. PMID- 26152141 TI - Coffee brewing technique as a confounder in observational studies. PMID- 26152142 TI - Exploring bi-directional and SMS messaging for communications between Public Health Agencies and their stakeholders: a qualitative study. AB - BACKGROUND: Communication technologies that enable bi-directional/two-way communications and cell phone texting (SMS) between public health agencies and their stakeholders may improve public health surveillance, ensure targeted distribution of alerts to hard-to-reach populations, reduce mortality and morbidity in an emergency, and enable a crucial feedback loop between public health agencies and the communities they serve. Building on prior work regarding health care provider preferences for receiving one-way public health communications by email, fax or SMS, we conducted a formative, exploratory study to understand how a bi-directional system and the incorporation of SMS in that system might be used as a strategy to send and receive messages between public health agencies and community-based organizations which serve vulnerable populations, health care providers, and public health workers. Our research question: Under what conditions and/or situations might public health agencies utilize bi-directional and/or SMS messaging for disseminating time-sensitive public health information (alerts, advisories, updates, etc.) to their stakeholders? METHODS: A mixed methods (qualitative and quantitative) study was conducted between April and July 2014. Data collection included a survey distributed to health care providers and semi-structured interviews with providers, community- and government-based organization leaders and directors, and public health agency internal workforce staff. Survey respondents and interviewees were asked about their exposure to public health messages, how these messages are received and how the information in these messages are handled, and in what situations (for example, a local vs. a national event, a pandemic or emergency vs. a health update) a bi-directional and/or SMS messaging system might improve communications between public health agencies and their stakeholder group. Interview and survey data were qualitatively analyzed. Thematic codes were quantitized into dichotomous variables of 0 or 1 on a per respondent basis to enumerate the presence or absence of each thematic code, enable quantitative analysis, and inform interpretation of findings. RESULTS: Five major themes emerged from synthesizing survey and interview results: 1) Regardless of situational context (emergency vs. non-urgent) and message recipient (stakeholder group), e-mail is a favored modality for receiving public health messages; 2) The decision to use bi-directional, SMS or multiple communication strategies is complex and public health agencies' need to manage messaging concerns/barriers and benefits for all parties; 3) Both public health agencies and their stakeholders share similar values/uses and concerns regarding two-way public health messaging and SMS; 4) Public health is highly trusted, thus thoughtful, effective messaging will ensure continuation of this goodwill; and 5) Information reciprocity between public health agencies and stakeholders who share their information is essential. CONCLUSIONS: Multiple communication strategies might be utilized but the choice of a specific strategy needs to balance message content (emergency vs. routine communications), delivery (one- vs. two-way), channel (SMS, email, etc.), and public health agency burden with stakeholder preferences and technical capabilities, all while mitigating the risk of message overload and disregard of important communications by recipients. PMID- 26152143 TI - Pharmacophore-Based Virtual Screening for Identification of Novel Neuraminidase Inhibitors and Verification of Inhibitory Activity by Molecular Docking. AB - Oseltamivir and Zanamivir are two of the recently licensed neuraminidase inhibitors used for the treatment of influenza. However, alternative antiviral agents are needed due to the development of resistant mutations in Oseltamivir subtype H1N1 and H5N1 avian influenza A viruses, the latter being a highly pathogenic avian virus that can be transferred to humans upon immediate contact with H5N1 infected poultry or surface. Novel drug inhibiting group 1 neuraminidases may potentially be developed through addition of extra substituent moieties to existing inhibitor skeletons. Another approach involves virtual screening of existing inhibitor skeletons which we have reported using novel ligands of H5N1 via virtual screening approach. In this study, we have used 3D structure of avian influenza virus H5N1 neuraminidase as target against a ligand dataset of four known neuraminidase inhibitors for in silico analysis. Using the dataset of known four inhibitors, a pharmacophore model was developed using ligand-based pharmacophore modeling strategy. This pharmacophore model was then used for virtual screening of natural compounds library taken from Princeton database. New hits that shared features of our pharmacophore model and binding interactions with receptor residues have been reported in this study. As more antiviral agents are required, the reported hits in our study may play an important role as novel antiviral agents against influenza virus. PMID- 26152144 TI - Synthesis, Anticancer Evaluation and Docking Study of 3- Benzyloxyhydantoin Derivatives. AB - A series of 3-benzyloxyhydantoin derivatives were designed and synthesized by introducing hydroxyurea pharmacophore into hydantoin rigid scaffold. The cytotoxic activities of the target compounds were evaluated in vitro against three cancer cell lines. Compounds 5b, 5c, 5e, 5g, 6c and 6g displayed high activity on all of the three cancer cell lines and the most promising compounds were 5g, 6g with IC50 values of 0.04 and 0.01uM. Binding of derivatives for the ribonucleotide reductase (RR) was investigated by use of molecular docking studies. Our findings show that modification at the C5 position of hydantoin with isopropyl or isobutyl was favorable to increasing binding affinity to the active site of the RR receptor and antiproliferative activity. PMID- 26152145 TI - Biological Evaluation of Azomethine-dihydroquinazolinone Conjugates as Cancer and Cholinesterase Inhibitors. AB - In an attempt to discover novel anti-cancer agents and potent cholinesterase inhibitors, 11 azomethine-dihydroquinazolinone conjugates were evaluated against lung carcinoma cells and cholinesterases. Most of the compounds exhibited significant cytotoxicity at low micromolar concentrations and were less toxic to normal cells. After 24 h incubation period, 2i showed maximum cytotoxicity. The 4 bromine substituted compounds showed higher acetylcholinesterase (AChE) inhibitory activity than other screened compounds. The most active compound 2c, among the series, had an IC50 value 209.8 uM against AChE. The tested compounds showed less inhibition against butyrylcholinesterase. Molecular docking studies were performed in order to investigate the plausible binding modes of synthesized compounds. The compounds can be further optimized to treat cancer and Alzheimer's disease. These derivatives may open new pathways for introducing new therapies for curing cancer and senile dementia. PMID- 26152147 TI - Sepsis in children. PMID- 26152146 TI - Healthy weight and lifestyle advertisements: an assessment of their persuasive potential. AB - This study aimed to identify and analyse the content of previously produced and aired adult-targeted public health advertisements (ads) addressing weight, nutrition or physical activity internationally. Ads were identified via keyword searches of Google, YouTube and websites of relevant government agencies and health organizations, and were eligible for inclusion if they were: in English; produced between 2007 and 2012; targeted at adults; <=60 s; not promoting a particular commercial brand of food, fitness or weight loss product. Of the 99 ads coded, 59% featured supportive/encouraging messages, 36% presented information about health consequences and 17% focussed on social norms/acceptability issues. Supportive/encouraging messages were more frequently used in physical activity ads, while there were a higher proportion of messages about health consequences in weight ads. Execution style differed across lifestyle topics, with simulation/animation more common in nutrition ads and graphic images and negative personal testimonials in weight ads. Ads addressing weight were more likely to evoke high negative emotion and include potentially stigmatizing content. Understanding how weight and lifestyle issues have been addressed in recent public health advertising will help guide future efforts to test the effectiveness of different message types in facilitating positive behaviour changes. PMID- 26152149 TI - Cabozantinib in Thyroid Cancer. AB - Cabozantinib is an oral once-daily multitarget tyrosine kinase inhibitor of MET, VEGFR2, RET, acting against KIT, AXL, FLT3 and Tie-2. Cabozantinib has shown anti cancer effects in preclinical and clinical models of cancers derived from both epithelial and mesenchymal origins [prostate cancer, non small lung cancer, medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC), renal cell carcinoma, etc.]. In a Phase III clinical study, cabozantinib improved PFS (11.2 months versus 4.0 months in the placebo group) of patients with MTC (independently of age, bone metastases, RET status and prior treatment). Cabozantinib was approved in 2012 by FDA for metastatic MTC and in 2013 by EMA. Cabozantinib has been also evaluated in metastatic DTC patients, because they have activation on tyrosine kinases, including MET, VEGFR2 and RET, suggesting the possible use of cabozantinib in metastatic DTC. Actually, two Phase II trials of cabozantinib in DTC patients resistant to RAI are ongoing. To increase the antineoplastic effect of cabozantinib, and to overcome the occurrence of drug resistance, combination studies with other anticancer agents are ongoing. In conclusion, cabozantinib has shown to exert an important therapeutic effect in patients with MTC improving PFS. In DTC patients, cabozantinib has shown promising results. PMID- 26152148 TI - Cardiovascular mortality among a cohort of hypertensive and normotensives in Rio de Janeiro - Brazil - 1991-2009. AB - BACKGROUND: Although there is strong evidence of the benefits of antihypertensive treatment, the high prevalence of this important cardiovascular risk factor and its complications, as well as the low control rates of hypertension observed in many studies justify the investigation of these relationships in population studies. The objective was to investigate the ratio of cardiovascular disease mortality between hypertensives (non-treated, controlled and uncontrolled) and non-hypertensives in a cohort of a population sample of adults living in Ilha do Governador, Rio de Janeiro state, Brazil, who were classified in a survey conducted in 1991 and 1992 and whose death certificates were sought 19 years later. METHODS: A cohort study was performed on probabilistic linkage between data from an epidemiological study of hypertension performed in Ilha do Governador, in Rio de Janeiro, Brazil (1991 to 1992) and data from the Mortality Information System of Rio de Janeiro (1991 to 2009). The survey aimed to estimate the prevalence of hypertension and other cardiovascular risk factors in 1,270 adults aged 20 years or older selected through a probabilistic sampling of households at three economic levels (low, middle and high income). We performed a probabilistic record linkage of these databases and estimated the risk of cardiovascular death using Kaplan-Meier method to plot survival curves and Cox proportional hazards models comparing hypertensive subjects all together, and by hypertension subgroups: untreated, controlled, and uncontrolled hypertensives with non-hypertensive ones. RESULTS: A total of 170 deaths occurred, of which 31.2 % attributed to cardiovascular causes. The hazard ratio for cardiovascular death was 6.1 times higher (95 % CI 2.7 - 13.7) in uncontrolled hypertensive patients relative to non-hypertensive patients. The hazard ratios for untreated hypertensive and controlled hypertensive patients were 2.7 times (95 % CI 1.1 - 6.3) and 2.1 times (95 % CI 0.38 - 11.5) higher than for normotensive patients, respectively. CONCLUSION: The present study demonstrated a higher cardiovascular death risk among hypertensive than among non-hypertensive ones that is not associated uniquely to treatment, because uncontrolled hypertensives demonstrated a greater risk than untreated ones. Although the subgroups of hypertensive individuals were susceptible to changes in their classification over the 19 years of the study, the baseline classification was consistent with a worse prognosis in these individuals. PMID- 26152150 TI - pH Gradient Reversal: An Emerging Hallmark of Cancers. AB - Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer "pH gradient reversal". Normalizing pH gradient reversal through inhibition of various proton transporters such as Na(+)-H(+) exchanger (NHE), Vacuolar-type H(+)-ATPase (V-ATPase), H(+)/K(+)-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them. PMID- 26152151 TI - Recent Patents on Thiazole Derivatives Endowed with Antitumor Activity. AB - Cancer is a disease of remarkable importance in the world today and is projected to become the primary cause of death within the coming years, therefore the design and development of new antitumor agents is one of the most pressing research areas in medicinal chemistry. Considering the importance of thiazole ring as scaffold present in a wide range of therapeutic agents, the medicinal chemists have been encouraged to synthesize a large number of novel antitumors bearing this heterocycle, which furnish extensive synthetic possibilities due to the presence of several reaction sites. The present review describes the patents from 2008 to present concerning new thiazole compounds useful for the development of new drug molecules. It has been divided according to the molecular target and describes the pathways involved in the biological activities and the structure of the most potent compounds, together with the screening results. PMID- 26152152 TI - [Continue animal research? A necessity for biological knowledge and medical progress: a scientific or philosophical question?]. PMID- 26152153 TI - [Metabolic switch in pluripotent stem cells: identification of a novel pathway]. PMID- 26152154 TI - [A novel therapeutic approach to fight osteoporosis: disrupt osteoclast activity without affecting bone formation]. PMID- 26152155 TI - [Involvement of food additives in intestinal inflammation and metabolic syndrome in mice]. PMID- 26152156 TI - [SH3BP2 heterozygous mutation amplifies macrophage inflammatory responses to infection in a mouse model of cherubism]. PMID- 26152157 TI - [Thymic epithelial populations: recently reunified through a unique stem cell]. PMID- 26152158 TI - [NDP52, autophagy and pathogens: "The war then ceased for lack of combatants"]. PMID- 26152159 TI - [Fundamental mechanisms of amyloid fibril formation by alpha-synuclein in Parkinson's disease: quantitative modelling]. PMID- 26152160 TI - [Guanylate binding proteins: new proteins from the cell host cytosol involved in antibacterial immunity]. PMID- 26152161 TI - [Nuclear export inhibitors as a potential therapy for multiple sclerosis]. PMID- 26152162 TI - [Activated platelets help to repair teeth through recruitment of pulpal stem cells]. PMID- 26152163 TI - [Single neurons recording with non invasive microelectrodes]. PMID- 26152164 TI - [miR-122 continues to surprise us]. PMID- 26152165 TI - [Dual role for prostaglandin D2 in intestinal epithelial homeostasis]. AB - Prostaglandin D2 (PGD2) and derivatives are lipid mediators involved in the control of the intestinal epithelial barrier homeostasis. Their involvement in the pathophysiology of chronic inflammatory bowel disease (IBD) is still debated. Several results highlight the duality of PGD2 as an anti- or pro-inflammatory mediator. This duality seems to be related to a differential expression of its receptors by intestinal epithelial cells and the surrounding immunocompetent cells. The enteric glial cells from the enteric nervous system (ENS) express the lipocalin-type-prostaglandin D synthase and secrete PGD2 and 15d-PGJ2. The protective role of the ENS in the homeostatic control of the epithelial intestinal barrier and its involvement in the pathogenesis of IBD have already been demonstrated. Thus, these lipid mediators seem to be new actors of the neuro glio-epithelial unit and could play a crucial role maintaining gut barrier integrity. PMID- 26152166 TI - [About the ribosomal biogenesis in human]. AB - Ribosomes are cellular ribonucleoprotein particles required for a fundamental mechanism, translation of the genetic information into proteins. Ribosome biogenesis is a highly complex pathway involving many maturation steps: ribosomal RNA (rRNA) synthesis, rRNA processing, pre-rRNA modifications, its assembly with ribosomal proteins in the nuceolus, export of the subunit precursors to the nucleoplasm and the cytoplasm. Ribosome biogenesis has mainly being investigated in yeast during these last 25 years. However, recent works have shown that, despite many similarities between yeast and human ribosome structure and biogenesis, human pre-rRNA processing is far more complex than in yeast. In order to better understand diseases related to a malfunction in ribosome synthesis, the ribosomopathies, research should be conducted directly in human cells and animal models. PMID- 26152167 TI - [Intercellular transmission of HTLV-1: not all mechanisms have been revealed]. AB - HTLV-1 is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and of HTLV-1-Associated Myelopathy/tropical spastic paraparesis (HAM/TSP). It is mainly detected in CD4+ lymphocytes in vivo, but proviral genomes have also been detected although less frequently, in CD8+ T lymphocytes, B lymphocytes, monocytes, macrophages, dendritic cells and other non-lymphoid cells. Virus spread is highly dependent on cell-cell contact. This mode of transmission is correlated with an increased ability of infected cells to migrate, a property linked to cytoskeleton reorganization induced by the viral Tax protein. Cell-to cell transmission relies on at least three non-exclusive molecular pathways. First, a specialized area, the "virological synapse'' (VS) promotes direct transmission of budding HTLV-1 particles into a synaptic cleft formed between infected and uninfected cells. Second, HTLV-1 particles accumulate at the plasma membrane of infected cells in a biofilm-like extracellular viral assembly that resembles a bacterial biofilm. Viral biofilm is rapidly transmitted to uninfected cells when infected cells contact target cells. Finally, membrane extensions called inter-cellular conduits facilitate HTLV-1 proteins transfer from infected to uninfected target cells, and may stabilize cell-cell contacts. The aim of this review is to summarize the molecular mechanisms of these HTLV-1 transmission pathways. PMID- 26152168 TI - [Looking through zebrafish to study host-pathogen interactions]. AB - The zebrafish offers many advantages that motivated and validated its use to study the virulence of numerous human pathogens, including viruses, bacteria and fungi. Its immune system is homologous to the one of mammals. The optical transparency of zebrafish embryos allows non-invasive and real-time monitoring of the infection processes through the use of imaging techniques. The zebrafish is therefore a useful and powerful model to study host-pathogen interactions at a cellular level. It may be used to describe pathophysiological events and subversion mechanisms that are specific to each pathogen. In addition to increasing our understanding of the host immune defense, this model is of high potential for medical application, being particularly amenable to high-throughput screening for the discovery of new anti-infective molecules. PMID- 26152169 TI - [IgM+IgD+CD27+ B cells in human: an essential role in the protection against encapsulated bacteria]. AB - In humans, CD27+ blood B cells with mutated immunoglobulin (Ig) receptors comprise two major populations: isotype-switched memory cells (IgG+ or IgA+CD27+) and IgM+IgD+CD27+ cells. While switched CD27+ cells are generated in germinal centers (GC) by T-dependent (TD) responses, the origin of IgM+IgD+CD27+ cells is still controversial. Data including ours support the view that these cells can develop and mutate along a GC-independent pathway and that they represent circulating marginal zone B (MZB) cells involved in T-independent (TI) responses. Our data provide evidence for a developmental diversification of these MZB cells, at least in very young children, outside of TD and TI immune responses. The identification of a human MZB cell precursor with NOTCH2-dependent differentiation properties further argue in favor of the existence of a MZB cell lineage in humans, like in rodents. At last, a role for Toll-like receptors in the development and/or maintenance of IgM+IgD+CD27+ B cells is proposed. PMID- 26152170 TI - [Biomimetic sensors in biomedical research]. AB - The recent research on both the synthesis of membrane proteins by cell-free systems and the reconstruction of planar lipid membranes, has led to the development of a cross-technology to produce biosensors or filters. Numerous biomimetic membranes are currently being standardized and used by the industry, such as filters containing aquaporin for water desalination, or used in routine at the laboratory scale, for example the bacteriorhodopsin as a light sensor. In the medical area, several fields of application of these biomimetic membranes are under consideration today, particularly for the screening of therapeutic molecules and for the developing of new tools in diagnosis, patient monitoring and personalized medicine. PMID- 26152171 TI - [Quality control of chemical libraries]. AB - The complete sequence of the human genome has been deciphered at the dawn of the new century. This historic event immediately challenged researchers with new needs both in terms of concepts and of working methods. Each scientific community considered how it could tackle these new challenges and it quickly became clear that using small chemical molecules would help discovering and characterizing the function of new proteins. The importance of the genes that the encode new proteins could thus be established in cells, organs and whole organisms. At the initiative of a handful of researchers, French chemists have organized the collection of their molecules and provided them to biologists. By doing so they killed two birds with one stone: on the one hand they created a unique opportunity to add value to their molecules by creating the first academic chemical library, and on the other hand they stimulated the launch of biologically active molecules discovery programs by biologists from the academic sector. It was necessary, however, to raise many compounds and ensure consistent quality control, which quickly became a priority for the chemical libraries to become reliable tools. PMID- 26152172 TI - [Modulating endoplasmic reticulum stress in the treatment of cancer]. AB - An imbalance of protein homeostasis caused by external or internal stress in the endoplasmic reticulum triggers the initiation of signalling pathways downstream of the IRE1, ATF6 and PERK sensors to a translational or transcriptional adaptive response known as UPR (Unfolded Protein Response). According to the intensity and duration of stress, the dual function of the UPR leads to either cell adaptation or cell death. UPR pathways in cancer cells are often altered and generally lead to an adaptation to an hostile environment. As the UPR becomes an emerging therapeutic target due to its increasing contribution to various diseases, we describe in this review various strategies that have been developed to discover new compounds enabling to manipulate the magnitude of ER stress in the context of cancer. PMID- 26152173 TI - [Surgical strategy to rescue the addicts]. AB - Since its successful application for the treatment of neurological disorders, deep brain stimulation (DBS) is currently also applied for the treatment of psychiatric disorders such as obsessive compulsive disorders or depression. DBS is being considered, or even applied, as a treatment for certain forms of addiction. We review here the cerebral structures aimed for such a strategy and discuss their respective positive and negative aspects. PMID- 26152174 TI - [ENCODE apophenia or a panglossian analysis of the human genome]. AB - In September 2012, a batch of more than 30 articles presenting the results of the ENCODE (Encyclopaedia of DNA Elements) project was released. Many of these articles appeared in Nature and Science, the two most prestigious interdisciplinary scientific journals. Since that time, hundreds of other articles dedicated to the further analyses of the Encode data have been published. The time of hundreds of scientists and hundreds of millions of dollars were not invested in vain since this project had led to an apparent paradigm shift: contrary to the classical view, 80% of the human genome is not junk DNA, but is functional. This hypothesis has been criticized by evolutionary biologists, sometimes eagerly, and detailed refutations have been published in specialized journals with impact factors far below those that published the main contribution of the Encode project to our understanding of genome architecture. In 2014, the Encode consortium released a new batch of articles that neither suggested that 80% of the genome is functional nor commented on the disappearance of their 2012 scientific breakthrough. Unfortunately, by that time many biologists had accepted the idea that 80% of the genome is functional, or at least, that this idea is a valid alternative to the long held evolutionary genetic view that it is not. In order to understand the dynamics of the genome, it is necessary to re-examine the basics of evolutionary genetics because, not only are they well established, they also will allow us to avoid the pitfall of a panglossian interpretation of Encode. Actually, the architecture of the genome and its dynamics are the product of trade-offs between various evolutionary forces, and many structural features are not related to functional properties. In other words, evolution does not produce the best of all worlds, not even the best of all possible worlds, but only one possible world. PMID- 26152175 TI - [The legacy of Mary F. Lyon (1925-2014)]. PMID- 26152176 TI - [The return of germline gene therapy]. AB - The recent development of a powerful and flexible genome editing technique (the CRISP-cas9 method) accelerates tremendously the production of animal models and will significantly enhance the perspectives of (somatic) gene therapy. However, it also raises a real possibility of germline modifications in humans, with therapeutic aims or for "improvement": this raises thorny ethical questions that are no longer theoretical (as in the 1990s) but will have to be faced in the very near future. PMID- 26152177 TI - [Publish in m/s today and tomorrow... Students express themselves]. PMID- 26152178 TI - Comparison of clinical characteristics and outcomes between aspiration pneumonia and community-acquired pneumonia in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients often have dysphagia through age and several co-morbidities, leading to aspiration pneumonia (AsP). COPD patients also have increased risk of developing community-acquired pneumonia (CAP). Using a national inpatient database in Japan, we aimed to compare clinical characteristics and outcomes between AsP and CAP in COPD patients and to verify the factors that affect in-hospital morality. METHODS: We retrospectively collected data on COPD patients (age >=40 years) who were admitted for AsP or CAP in 1,165 hospitals across Japan between July 2010 and May 2013. We performed multivariable logistic regression analyses to examine the association of various factors with all-cause in-hospital mortality for AsP and CAP. RESULTS: Of 87,330 eligible patients, AsP patients were more likely to be older, male and have poorer general condition and more severe pneumonia than those with CAP. In-hospital mortality in the AsP group was 22.7% and 12.2% in the CAP group. After adjustment for patient background, AsP patients had significantly higher mortality than CAP patients (adjusted odds ratio, 1.19; 95% confidence interval, 1.08-1.32). Subgroup analyses showed higher mortality to be associated with male gender, underweight, dyspnea, physical disability, pneumonia severity, and several co-morbidities. Further, older age and worse level of consciousness were associated with higher mortality in the CAP group, whereas those were not associated in the AsP group. CONCLUSIONS: Clinical characteristics differed significantly between AsP and CAP in COPD patients. AsP patients had significantly higher mortality than those with CAP. PMID- 26152179 TI - Primary and Secondary Prevention of Acute Coronary Syndromes: The Role of the Statins. AB - Poor prognosis is strongly associated with Acute Coronary Syndrome (ACS) and, even though a number of treatment strategies are available, the incidence of subsequent serious complications after an acute event is still high. Statins are hypolipidemic factors and recent studies have demonstrated that they have a protective role during the process of atherogenesis and that they reduce mortality caused by cardiovascular diseases. This review tries to reveal the function of the statins as a component of the primary and secondary action of acute coronary syndrome and to describe the lifestyle changes that have the same effect as the use of statins. PMID- 26152180 TI - Circle fully commits to collaborating with NHS on service transformation. PMID- 26152181 TI - Authors' reply to Hamilton and King. PMID- 26152182 TI - Utility of copeptin and standard inflammatory markers in the diagnostics of upper and lower urinary tract infections. AB - BACKGROUND: A new serum marker of inflammation copeptin (CPP) a stable C-terminal pro-vasopressin was assessed along with conventional markers such as C-reactive protein (CRP), procalcitonin (PCT) and IL-6 to discriminate between lower and upper bacterial urinary tract infections (UTI). METHODS: Study population comprised 45 patients including 13 with lower UTI (L-UTI) and 32 with upper UTI (U-UTI) and 24 healthy controls. Serum markers, blood cultures and urine cultures were assessed before commencing antibiotic treatment and repeated 24, 48 h and 7 days thereafter. Receiver operating curves (ROC) were plotted to assess a diagnostic utility of different inflammatory markers. RESULTS: Before antibiotic therapy all inflammatory markers including serum CPP (2821.1 +/- 1072.4 pg/ml vs. 223.8 +/- 109.3 pg/ml; p < 0.05) were higher in UTI than in controls. CPP was not different between L- and U-UTI (2253 +/- 1323 pg/ml vs 3051 +/- 1178 pg/ml; p = 0.70) despite significant differences in hsCRP (2.09 +/- 1.7 mg/dl vs 127.3 +/- 62.4 mg/dl; p < 0.001), PCT (0.05 +/- 0 vs 5.02 +/- 0.03 ng/ml p < 0.001) and IL 6 (22.5 +/- 1.6 vs 84.8 +/- 67 pg/ml p < 0.001). For U-UTI the areas under the ROC curves were 1.0 for both hsCRP and CPP, 0.94 for PCT and 0.7 for IL-6 and for L-UTI 0.571, 1, 0.505 and 0.73, respectively. After 7 days of treatment all markers decreased in parallel to clinical response. CONCLUSION: Although elevated serum copeptin may become a marker of UTI it seems to be inferior compared to traditional serum inflammation markers for differentiation of bacterial infections involving upper and lower urinary tract. PMID- 26152183 TI - Dupuytren's contractures associated with the BRAF inhibitor vemurafenib: a case report. AB - INTRODUCTION: Two previous cases of the development of Dupuytren's contractures were reported in association with BRAF inhibitor treatment for BRAF V600E mutation-positive metastatic melanoma and metastatic papillary thyroid carcinoma. We reported on a third case with a slower onset of presentation. CASE PRESENTATION: A 66-year-old white man was diagnosed with a BRAF V600E mutated metastatic cutaneous melanoma. He was commenced on oral vemurafenib 960 mg twice daily. A marked response was achieved for his metastatic disease. He noticed a change of his hair characteristics and a feeling of "lumps" in both palms by 6 months. By 9 months, classical Dupuytren's contracture was apparent. CONCLUSIONS: Dupuytren's contracture is not a known side effect of BRAF inhibitor treatment. The timeline for the development of Dupuytren's contracture on BRAF inhibitor treatment is not well defined. Although the etiology of Dupuytren's contracture is unknown, an increase in tumor necrosis factor has been demonstrated to be a possible mechanism. BRAF inhibition has been shown to increase immune reaction in the tumor microenvironment and is associated with high serum tumor necrosis factor level. We propose that an increased level of tumor necrosis factor associated with BRAF inhibition may increase the risk of the development of Dupuytren's contractures. PMID- 26152184 TI - Authors' reply to Laurent. PMID- 26152185 TI - A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection. AB - Emerging evidence suggests a role for purinergic signaling in the activation of multiprotein intracellular complexes called inflammasomes, which control the release of potent inflammatory cytokines, such as interleukin (IL) -1beta and 18. Porphyromonas gingivalis is intimately associated with periodontitis and is currently considered one of the pathogens that can subvert the immune system by limiting the activation of the NLRP3 inflammasome. We recently showed that P. gingivalis can dampen eATP-induced IL-1beta secretion by means of its fimbriae in a purinergic P2X7 receptor-dependent manner. Here, we further explore the role of this purinergic receptor during eATP-induced IL-1beta processing and secretion by P. gingivalis-infected macrophages. We found that NLRP3 was necessary for eATP induced IL-1beta secretion as well as for caspase 1 activation irrespective of P. gingivalis fimbriae. Additionally, although the secretion of IL-1beta from P. gingivalis-infected macrophages was dependent on NLRP3, its adaptor protein ASC, or caspase 1, the cleavage of intracellular pro-IL-1beta to the mature form was found to occur independently of NLRP3, its adaptor protein ASC, or caspase 1. Our in vitro findings revealed that P2X7 receptor has a dual role, being critical not only for eATP-induced IL-1beta secretion but also for intracellular pro-IL-1beta processing. These results were relevant in vivo since P2X7 receptor expression was upregulated in a P. gingivalis oral infection model, and reduced IFN-gamma and IL-17 were detected in draining lymph node cells from P2rx7(-/-) mice. Furthermore, we demonstrated that P2X7 receptor and NLRP3 transcription were modulated in human chronic periodontitis. Overall, we conclude that the P2X7 receptor has a role in periodontal immunopathogenesis and suggest that targeting of the P2X7/NLRP3 pathway should be considered in future therapeutic interventions in periodontitis. PMID- 26152186 TI - Cellular Components Mediating Coadherence of Candida albicans and Fusobacterium nucleatum. AB - Candida albicans is an opportunistic fungal pathogen found as part of the normal oral flora. It can be coisolated with Fusobacterium nucleatum, an opportunistic bacterial pathogen, from oral disease sites, such as those involved in refractory periodontitis and pulp necrosis. The physical coadherence between these 2 clinically important microbes has been well documented and suggested to play a role in facilitating their oral colonization and colocalization and contributing to polymicrobial pathogenesis. Previous studies indicated that the physical interaction between C. albicans and F. nucleatum was mediated by the carbohydrate components on the surface of C. albicans and the protein components on the Fusobaterium cell surface. However, the identities of the components involved still remain elusive. This study was aimed at identifying the genetic determinants involved in coaggregation between the 2 species. By screening a C. albicans SN152 mutant library and a panel of F. nucleatum 23726 outer membrane protein mutants, we identified FLO9, which encodes a putative adhesin-like cell wall mannoprotein of C. albicans and radD, an arginine-inhibitable adhesin encoding gene in F. nucleatum that is involved in interspecies coadherence. Consistent with these findings, we demonstrated that the strong coaggregation between wild-type F. nucleatum 23726 and C. albicans SN152 in an in vitro assay could be greatly inhibited by arginine and mannose. Our study also suggested a complex multifaceted mechanism underlying physical interaction between C. albicans and F. nucleatum and for the first time revealed the identity of major genetic components involved in mediating the coaggregation. These observations provide useful knowledge for developing new targeted treatments for disrupting interactions between these 2 clinically relevant pathogens. PMID- 26152187 TI - NF-kappaB Enhances Androgen Receptor Expression through 5'-UTR Binding in Gingival Cells. AB - Dihydropyridine-induced gingival overgrowth (DIGO) is a side effect observed in patients treated for hypertension. The disease is aggravated by inflammation. Nifedipine (Nif), a dihydropyridine, causes gingival overgrowth by increasing the expression of the androgen receptor (AR). Furthermore, the proinflammatory cytokine interleukin 1beta (IL-1beta) induces collagen alpha1(I) expression through the AR in DIGO fibroblasts. These observations prompted us to investigate whether and how nuclear factor kappa B (NF-kappaB) affects AR expression in DIGO. Therefore, gingival fibroblasts obtained from the tissues of patients with DIGO and healthy subjects were stimulated with IL-1beta, Nif, or both. mRNA and protein expression was detected with real-time polymerase chain reaction and Western blotting. High correlation coefficients were observed for the mRNA expression of the AR, connective tissue growth factor, and collagen alpha1(I) induced by both drugs. Western blot analysis showed that IL-1beta and Nif increased and activated NF-kappaB more in DIGO cells than in healthy cells. An electrophoretic mobility shift assay demonstrated that the promoter and 5' untranslated regions (5'-UTRs) of the AR gene contains 3 binding sites for the NF kappaB p65 subunit. A chromatin immunoprecipitation assay revealed that the NF kappaB p65 subunit was associated with AR 5'-UTRs in gingival fibroblasts. A site directed mutagenesis study indicated that a mutation of NF-kappaB binding sites reduced Nif- and IL-1beta-induced AR promoter activities. Collectively, these data indicate that NF-kappaB is an essential transcriptional regulator of AR gene expression and thus plays a crucial role in collagen overproduction in DIGO fibroblasts. PMID- 26152188 TI - Microspore culture reveals complex meiotic behaviour in a trigenomic Brassica hybrid. AB - BACKGROUND: Development of synthetic allohexaploid Brassica (2n = AABBCC) would be beneficial for agriculture, as allelic contributions from three genomes could increase hybrid vigour and broaden adaptation. Microspore culture of a near allohexaploid hybrid derived from the cross (B. napus * B. carinata) * B. juncea was undertaken in order to assess the frequency and distribution of homologous and homoeologous crossovers in this trigenomic hybrid. SNP and SSR molecular markers were used to detect inheritance of A, B and C genome alleles in microspore-derived (MD) progeny. SNP allele copy number was also assessed. The MD progeny were also compared to progeny derived by self-pollination and open pollination for fertility (estimated by self-pollinated seed set and pollen viability) and DNA ploidy (measured by flow cytometry). RESULTS: In the trigenomic hybrid, homologous chromosome pairs A(j)-A(n), B(j)-B(c) and C(n)-C(c) had similar meiotic crossover frequencies and segregation to that previously observed in established Brassica species, as demonstrated by marker haplotype analysis of the MD population. Homoeologous pairing between chromosomes A1-C1, A2 C2 and A7-C6 was detected at frequencies of 12-18 %, with other homoeologous chromosome regions associating from 8 % (A3-C3) to 0-1 % (A8-C8, A8-C9) of the time. Copy number analysis revealed eight instances of additional chromosomes and 20 instances of chromosomes present in one copy in somatically doubled MD progeny. Presence of chromosome A6 was positively correlated with self-pollinated seed set and pollen viability in the MD population. Many MD progeny were unable to produce self-pollinated seed (76 %) or viable pollen (53 %), although one MD plant produced 198 self-pollinated seeds. Average fertility was significantly lower in progeny obtained by microspore culture than progeny obtained by self pollination or open-pollination, after excluding MD progeny which had not undergone chromosome doubling. CONCLUSIONS: Based on SNP data analysis of the microspore-derived progeny, crossover frequency per chromosome in the allohexaploid hybrid was found to be similar to that in established Brassica species, suggesting that the higher chromosome number did not significantly disrupt cellular regulation of meiosis. SNP allele copy number analysis revealed the occurrence not only of homoeologous duplication/deletion events but also other cryptic duplications and deletions that may have been the result of mitotic instability. Microspore culture simplified the assessment of chromosome behaviour in the allohexaploid hybrid but yielded progeny with lower fertility and a greater range of ploidy levels compared to progeny obtained by self- or open pollination. PMID- 26152189 TI - False negative pericardial Focused Assessment with Sonography for Trauma examination following cardiac rupture from blunt thoracic trauma: a case report. AB - INTRODUCTION: The Focused Assessment with Sonography for Trauma examination is an invaluable tool in the initial assessment of any injured patient. Although highly sensitive and accurate for identifying hemoperitoneum, occasional false negative results do occur in select scenarios. We present a previously unreported case of survival following blunt cardiac rupture with associated negative pericardial window due to a concurrent pericardial wall laceration. CASE PRESENTATION: A healthy 46-year-old white woman presented to our level 1 trauma center with hemodynamic instability following a motor vehicle collision. Although her abdominal Focused Assessment with Sonography for Trauma windows were positive for fluid, her pericardial window was negative. After immediate transfer to the operating room in the setting of persistent instability, a subsequent thoracotomy identified a blunt cardiac rupture that was draining into the ipsilateral pleural space via an adjacent tear in the pericardium. The cardiac injury was controlled with digital pressure, resuscitation completed, and then repaired using standard cardiorrhaphy techniques. Following repair of her injuries (left ventricle, left atrial appendage, and liver), her postoperative course was uneventful. CONCLUSIONS: Evaluation of the pericardial space using Focused Assessment with Sonography for Trauma is an important component in the initial assessment of the severely injured patient. Even in cases of blunt mechanisms however, clinicians must be wary of occasional false negative pericardial ultrasound evaluations secondary to a concomitant pericardial laceration and subsequent decompression of hemorrhage from the cardiac rupture into the ipsilateral pleural space. PMID- 26152190 TI - A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice. AB - We found that the tryptic digest of Alaska pollack protein exhibits a glucose lowering effect in KK-Ay mice, a type II diabetic model. We then searched for glucose-lowering peptides in the digest. Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) was identified from a peak of the HPLC fraction selected based on the glucose-lowering activity in an insulin resistance test using ddY mice. ANGEVAQWR (3 mg kg(-1)) decreased the blood glucose level after intraperitoneal administration. Among its fragment peptides, the C-terminal tripeptide, Gln-Trp Arg (QWR, 1 mg kg(-1)), lowered the blood glucose level, suggesting that the C terminal is critical for glucose-lowering activity. QWR also enhanced glucose uptake into C2C12, a mouse skeletal muscle cell line. QWR did not induce the phosphorylation of serine/threonine protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK). We also demonstrated that QWR lowered the blood glucose level in NSY and KK-Ay, type II diabetic models. PMID- 26152191 TI - Induction of rapid and selective cell necrosis in Drosophila using Bacillus thuringiensis Cry toxin and its silkworm receptor. AB - BACKGROUND: Genetic ablation of target cells is a powerful tool to study the origins and functions of cells, tissue regeneration, or pathophysiology in a human disease model in vivo. Several methods for selective cell ablation by inducing apoptosis have been established, using exogenous toxins or endogenous proapoptotic genes. However, their application is limited to cells with intact apoptotic machinery. RESULTS: Herein, we established a method for inducing rapid and selective cell necrosis by the pore-forming bacterial toxin Cry1Aa, which is specifically active in cells expressing the Cry1Aa receptor (CryR) derived from the silkworm Bombyx mori. We demonstrated that overexpressing CryR in Drosophila melanogaster tissues induced rapid cell death of CryR-expressing cells only, in the presence of Cry1Aa toxin. Cry/CryR system was effective against both proliferating cells in imaginal discs and polyploid postmitotic cells in the fat body. Live imaging analysis of cell ablation revealed swelling and subsequent osmotic lysis of CryR-positive cells after 30 min of incubation with Cry1Aa toxin. Osmotic cell lysis was still triggered when apoptosis, JNK activation, or autophagy was inhibited, suggesting that Cry1Aa-induced necrotic cell death occurred independently of these cellular signaling pathways. Injection of Cry1Aa into the body cavity resulted in specific ablation of CryR-expressing cells, indicating the usefulness of this method for in vivo cell ablation. CONCLUSIONS: With Cry toxins from Bacillus thuringiensis, we developed a novel method for genetic induction of cell necrosis. Our system provides a "proteinous drill" for killing target cells through physical injury of the cell membrane, which can potentially be used to ablate any cell type in any organisms, even those that are resistant to apoptosis or JNK-dependent programmed cell death. PMID- 26152192 TI - Donor antigen-primed regulatory T cells permit liver regeneration and phenotype correction in hemophilia A mouse by allogeneic bone marrow stem cells. AB - INTRODUCTION: Cell replacement therapy may be considered as an alternate approach to provide therapeutic dose of plasma factor VIII (FVIII) in patients with hemophilia A (HA). However, immune rejection limits the use of allogeneic cells in this mode of therapy. Here, we have examined the role of donor major histocompatibility complex (MHC)-stimulated host CD4(+)CD25(+) regulatory T (Treg) cells in suppressing immune responses against allogeneic uncommitted (Lin( )) bone marrow cells (BMCs) for correction of bleeding disorder in HA mice. METHODS: Allogeneic donor Lin(-) BMCs were co-transplanted with allo-antigen sensitized Treg cells in HA mice having acetaminophen-induced acute liver injury. Plasma FVIII activity was determined by in vitro functional assay, and correction of bleeding phenotype was assessed on the basis of capillary blood clotting time and tail-clip challenge. The immunosuppression potential of the sensitized Treg cells on CD4(+) T cells was studied both in vitro and in vivo. Suppression of inflammatory reactions in the liver against the homed donor cells by sensitized Treg cells was analysed by histopathological scoring. Allo-specificity of sensitized Treg cells and long-term retention of immunosuppression were examined against a third-party donor and by secondary challenge of allogeneic donor cells, respectively. The engraftment and phenotype change of donor BMCs in the liver and their role in synthesis of FVIII and liver regeneration were also determined. RESULTS: Co-transplantation of allogeneic Lin(-) BMCs with sensitized Treg cells led to systemic immune modulation and suppression of inflammatory reactions in the liver, allowing better engraftment of allogeneic cells in the liver. Allo antigen priming led to allo-specific immune suppression even after 1 year of transplantation. Donor-derived endothelial cells expressed FVIII in HA mice, leading to the correction of bleeding phenotype. Donor-derived hepatocyte-like cells, which constitute the major fraction of engrafted cells, supported regeneration of the liver after acute injury. CONCLUSIONS: A highly proficient FVIII secreting core system can be created in regenerating liver by transplanting allogeneic Lin(-) BMCs in HA mice where transplantation tolerance against donor antigens can be induced by in vitro allo-antigen primed Treg cells. This strategy can be beneficial in treatment of genetic liver disorders for achieving prophylactic levels of the missing proteins. PMID- 26152194 TI - Review on sepsis in children did not mention important trial. PMID- 26152193 TI - The striking and unexpected cytogenetic diversity of genus Tanacetum L. (Asteraceae): a cytometric and fluorescent in situ hybridisation study of Iranian taxa. AB - BACKGROUND: Although karyologically well studied, the genus Tanacetum (Asteraceae) is poorly known from the perspective of molecular cytogenetics. The prevalence of polyploidy, including odd ploidy warranted an extensive cytogenetic study. We studied several species native to Iran, one of the most important centres of diversity of the genus. We aimed to characterise Tanacetum genomes through fluorochrome banding, fluorescent in situ hybridisation (FISH) of rRNA genes and the assessment of genome size by flow cytometry. We appraise the effect of polyploidy and evaluate the existence of intraspecific variation based on the number and distribution of GC-rich bands and rDNA loci. Finally, we infer ancestral genome size and other cytogenetic traits considering phylogenetic relationships within the genus. RESULTS: We report first genome size (2C) estimates ranging from 3.84 to 24.87 pg representing about 11 % of those recognised for the genus. We found striking cytogenetic diversity both in the number of GC-rich bands and rDNA loci. There is variation even at the population level and some species have undergone massive heterochromatic or rDNA amplification. Certain morphometric data, such as pollen size or inflorescence architecture, bear some relationship with genome size. Reconstruction of ancestral genome size, number of CMA+ bands and number of rDNA loci show that ups and downs have occurred during the evolution of these traits, although genome size has mostly increased and the number of CMA+ bands and rDNA loci have decreased in present-day taxa compared with ancestral values. CONCLUSIONS: Tanacetum genomes are highly unstable in the number of GC-rich bands and rDNA loci, although some patterns can be established at the diploid and tetraploid levels. In particular, aneuploid taxa and some odd ploidy species show greater cytogenetic instability than the rest of the genus. We have also confirmed a linked rDNA arrangement for all the studied Tanacetum species. The labile scenario found in Tanacetum proves that some cytogenetic features previously regarded as relatively constant, or even diagnostic, can display high variability, which is better interpreted within a phylogenetic context. PMID- 26152195 TI - The impact of sperm-expressed transcription factors on fate-mapping models. AB - Genetic lineage tracing has been used extensively in developmental biology. Many transcription factors expressed in sperm may induce Cre-mediated loxP recombination during early zygote development. In this study, we investigated the effect of sperm-expressed Cre on cell type-specific Cre-mediated loxP recombination in fate-mapping models of Tbx18+ progenitor cells. We found the recombination frequency in a reverse mating (RM) lineage was inconsistent with a normal Mendelian distribution. However, the recombination frequency in a positive mating (PM) lineage agreed with a Mendelian distribution. In the PM lineage, LacZ and EYFP were expressed in specific locations, such as the limb buds, heart, and hair follicles. Therefore, the reporter genes accurately and reliably traced cell differentiation in the PM lineage. In contrast, EYFP and LacZ were expressed throughout the embryo in the RM lineage. Thus, the reporter genes did not trace cell differentiation specifically in the RM lineage. Furthermore, Tbx18 mRNA and protein were expressed in the testicles of male mice, but almost no Tbx18 expression was detected in the ovaries of female mice. Similarly, reporter genes and Tbx18 were coexpressed in the seminiferous tubules and sperm cells of testicles. These results revealed that Cre-loxP-mediated pre-recombination in zygotes is due to Tbx18 expressed in testicle sperm cells when Cre is transmitted paternally. Our results indicate that Cre-mediated specific recombination in fate mapping models of sperm-expressed genes may be influenced by the paternal origin of Cre. Therefore, a careful experimental design is critical when using the Cre loxP system to trace spatial, temporal or tissue-specific fates. PMID- 26152196 TI - A Molecular Pharmacologist's Guide to G Protein-Coupled Receptor Crystallography. AB - G protein-coupled receptor (GPCR) structural biology has progressed dramatically in the last decade. There are now over 120 GPCR crystal structures deposited in the Protein Data Bank of 32 different receptors from families scattered across the phylogenetic tree, including class B, C, and Frizzled GPCRs. These structures have been obtained in combination with a wide variety of ligands and captured in a range of conformational states. This surge in structural knowledge has enlightened research into the molecular recognition of biologically active molecules, the mechanisms of receptor activation, the dynamics of functional selectivity, and fueled structure-based drug design efforts for GPCRs. Here we summarize the innovations in both protein engineering/molecular biology and crystallography techniques that have led to these advances in GPCR structural biology and discuss how they may influence the resulting structural models. We also provide a brief molecular pharmacologist's guide to GPCR X-ray crystallography, outlining some key aspects in the process of structure determination, with the goal to encourage noncrystallographers to interrogate structures at the molecular level. Finally, we show how chemogenomics approaches can be used to marry the wealth of existing receptor pharmacology data with the expanding repertoire of structures, providing a deeper understanding of the mechanistic details of GPCR function. PMID- 26152197 TI - The Complex Roles of MU-Opioid Receptor Phosphorylation: A Key Determinant in Receptor Signaling and Regulation. AB - This Commentary focuses on two articles in the October 2015 issue of Molecular Pharmacology that investigate the role of MU-opioid receptor phosphorylation in receptor agonist binding and desensitization. The work of Birdsong et al. and Yousuf et al. clearly highlights the complexity that researchers face when trying to assess the signaling and regulatory consequences of G protein-coupled receptor phosphorylation. PMID- 26152198 TI - Ligand Residence Time at G-protein-Coupled Receptors-Why We Should Take Our Time To Study It. AB - Over the past decade the kinetics of ligand binding to a receptor have received increasing interest. The concept of drug-target residence time is becoming an invaluable parameter for drug optimization. It holds great promise for drug development, and its optimization is thought to reduce off-target effects. The success of long-acting drugs like tiotropium support this hypothesis. Nonetheless, we know surprisingly little about the dynamics and the molecular detail of the drug binding process. Because protein dynamics and adaptation during the binding event will change the conformation of the protein, ligand binding will not be the static process that is often described. This can cause problems because simple mathematical models often fail to adequately describe the dynamics of the binding process. In this minireview we will discuss the current situation with an emphasis on G-protein-coupled receptors. These are important membrane protein drug targets that undergo conformational changes upon agonist binding to communicate signaling information across the plasma membrane of cells. PMID- 26152200 TI - Histone deacetylase 1 regulates tissue destruction in rheumatoid arthritis. AB - Emerging evidence implicates epigenetic mechanisms in the pathogenesis of rheumatoid arthritis (RA). In this study, we have investigated the role of histone deacetylase (HDAC) enzymes in RA synovial fibroblasts (RASFs), a key cellular mediator of cartilage and bone destruction and determined effects of HDAC1 inhibition on both RASF phenotype in vitro, and joint inflammation and damage in the collagen-induced arthritis (CIA) model. Expression of HDACs 1-11 messenger ribonucleic acid (mRNA) was compared between RASFs and osteoarthritic synovial fibroblast (OASFs) using quantitative polymerase chain reaction. HDAC1 expression in RASFs was inhibited using small interfering RNA (siRNA) technology to assess effects on invasiveness, migration, proliferation and apoptosis. Effects of HDAC1 knockdown (KD) on the transcriptome were assessed using gene microarrays. The effects of siRNA-mediated HDAC(KD) on clinical scores, tissue inflammation and damage were assessed on CIA up to 47 days following immunization. Expression of HDAC1 was significantly higher in RASFs than OASFs. HDAC1(KD) resulted in reduced proliferation, invasion and migration in vitro and transcriptome profiling revealed effects on expression of genes regulating proliferation migration and inflammation. Furthermore, inhibition of HDAC1 in CIA resulted in reduced joint swelling, cartilage and bone damage and lower tumor necrosis factor in joint tissue. These results implicate HDAC1 as an important mediator of tissue damage in RA and support the potential therapeutic utility of inhibitors of this enzyme. PMID- 26152199 TI - Non-coding genetic variants in human disease. AB - Genetic variants, including single-nucleotide variants (SNVs) and copy number variants (CNVs), in the non-coding regions of the human genome can play an important role in human traits and complex diseases. Most of the genome-wide association study (GWAS) signals map to non-coding regions and potentially point to non-coding variants, whereas their functional interpretation is challenging. In this review, we discuss the human non-coding variants and their contributions to human diseases in the following four parts. (i) Functional annotations of non coding SNPs mapped by GWAS: we discuss recent progress revealing some of the molecular mechanisms for GWAS signals affecting gene function. (ii) Technical progress in interpretation of non-coding variants: we briefly describe some of the technologies for functional annotations of non-coding variants, including the methods for genome-wide mapping of chromatin interaction, computational tools for functional predictions and the new genome editing technologies useful for dissecting potential functional consequences of non-coding variants. (iii) Non coding CNVs in human diseases: we review our emerging understanding the role of non-coding CNVs in human disease. (iv) Compound inheritance of large genomic deletions and non-coding variants: compound inheritance at a locus consisting of coding variants plus non-coding ones is described. PMID- 26152201 TI - A functional variant that affects exon-skipping and protein expression of SP140 as genetic mechanism predisposing to multiple sclerosis. AB - Several variants in strong linkage disequilibrium (LD) at the SP140 locus have been associated with multiple sclerosis (MS), Crohn's disease (CD) and chronic lymphocytic leukemia (CLL). To determine the causal polymorphism, we have integrated high-density data sets of expression quantitative trait loci (eQTL), using GEUVADIS RNA sequences and 1000 Genomes genotypes, with MS-risk variants of the high-density Immunochip array performed by the International Multiple Sclerosis Genetic Consortium (IMSGC). The variants most associated with MS were also correlated with a decreased expression of the full-length RNA isoform of SP140 and an increase of an isoform lacking exon 7. By exon splicing assay, we have demonstrated that the rs28445040 variant was the causal factor for skipping of exon 7. Western blots of peripheral blood mononuclear cells from MS patients showed a significant allele-dependent reduction of the SP140 protein expression. To confirm the association of this functional variant with MS and to compare it with the best-associated variant previously reported by GWAS (rs10201872), a case control study including 4384 MS patients and 3197 controls was performed. Both variants, in strong LD (r(2) = 0.93), were found similarly associated with MS [P values, odds ratios: 1.9E-9, OR = 1.35 (1.22-1.49) and 4.9E-10, OR = 1.37 (1.24 1.51), respectively]. In conclusion, our data uncover the causal variant for the SP140 locus and the molecular mechanism associated with MS risk. In addition, this study and others previously reported strongly suggest that this functional variant may be shared with other immune-mediated diseases as CD and CLL. PMID- 26152202 TI - Receptor tyrosine kinase mutations in developmental syndromes and cancer: two sides of the same coin. AB - Receptor tyrosine kinases (RTKs) are a family of ligand-binding cell surface receptors that regulate a wide range of essential cellular activities, including proliferation, differentiation, cell-cycle progression, survival and apoptosis. As such, these proteins play an important role during development and throughout life; germline mutations in genes encoding RTKs cause several developmental syndromes, while somatic alterations contribute to the pathogenesis of many aggressive cancers. This creates an interesting paradigm in which mutation timing, type and location in a gene leads to different cell signaling and biological responses, and ultimately phenotypic outcomes. In this review, we highlight the roles of RTKs in developmental disorders and cancer. The multifaceted roles of these receptors, their genetic signatures and their signaling during developmental morphogenesis and oncogenesis are discussed. Additionally, we propose that comparative analysis of RTK mutations responsible for developmental syndromes may shed light on those driving tumorigenesis. PMID- 26152203 TI - Breastfeeding-Friendly Erie County: Establishing the New York State Breastfeeding Friendly Practice Designation. AB - BACKGROUND: Primary care providers play an important role in encouraging and counseling pregnant and postpartum women to successfully breastfeed. OBJECTIVE: One objective of this 1-year grant was to establish the Breastfeeding Friendly Practice Designation criteria and process to identify and designate at least 5 primary care practices as New York State Breastfeeding Friendly Practices in a high-need, racially/ethnically diverse, urban county in New York with very low prevalence of breastfeeding initiation, exclusivity, and duration. METHODS: A partnership between the New York State Department of Health and the P(2) Collaborative of Western New York and United Way of Buffalo & Erie County's Healthy Start Healthy Future for All Coalition facilitated the development of the New York State Ten Steps to a Breastfeeding Friendly Practice, accompanying implementation guide, designation criteria, and model office policies. Practice staff and providers received on-site training and materials and participated in a virtual learning network to share their experiences, celebrate successes, and overcome challenges in implementing system changes. Practice staff completed a self-assessment survey at baseline and after implementation of the Ten Steps and submitted their written office breastfeeding policy for review. RESULTS: Fourteen practices met the criteria for designation and were recognized by the New York State Health Commissioner. CONCLUSION: The number of practices designated as Breastfeeding Friendly far exceeded the grant objective. Future efforts are directed at expanding this initiative statewide and determining the impact of the designation on breastfeeding outcomes. PMID- 26152204 TI - Promoting Breastfeeding-Friendly Hospital Practices: A Washington State Learning Collaborative Case Study. AB - BACKGROUND: Hospital breastfeeding support practices can affect breastfeeding outcomes. Learning collaboratives are an increasingly common strategy to improve practices in health care and have been applied to breastfeeding in many cases. OBJECTIVES: The aims of this study of the Evidence-Based Hospital Breastfeeding Support Learning Collaborative (EBBS LC) were to describe the perceptions of participants regarding the process and effectiveness of the EBBS LC, describe perceived barriers and facilitators to implementing the Ten Steps to Successful Breastfeeding, and identify additional actions and resources needed in future learning collaboratives. METHODS: Qualitative, semistructured telephone interviews were conducted with 13 key staff who represented 16 of the 18 participating hospitals. RESULTS: The learning collaborative was perceived positively by participants, meeting the expectations of 9 and exceeding the expectations of 4 persons interviewed. The most beneficial aspect of the program was its collaborative nature, and the most difficult aspect was the time required to participate as well as technological difficulties. The key barriers were staff time, staff changes, cost, and the difficulty of changing the existing practices of hospitals and communities. The key facilitating factors were supportive management, participation in multiple breastfeeding quality improvement projects, collecting data on breastfeeding outcomes, tangible resources regarding the Ten Steps, and positive community response. Participants in the EBBS LC stated that they would like to see the Washington State Department of Health create a resource-rich, centralized source of information for participants. CONCLUSION: This learning collaborative approach was valued by participants. Future efforts can be guided by these evaluation findings. PMID- 26152205 TI - Countries hit by Ebola need $700 m to rebuild health systems. PMID- 26152206 TI - Validation and selection of ODE based systems biology models: how to arrive at more reliable decisions. AB - BACKGROUND: Most ordinary differential equation (ODE) based modeling studies in systems biology involve a hold-out validation step for model validation. In this framework a pre-determined part of the data is used as validation data and, therefore it is not used for estimating the parameters of the model. The model is assumed to be validated if the model predictions on the validation dataset show good agreement with the data. Model selection between alternative model structures can also be performed in the same setting, based on the predictive power of the model structures on the validation dataset. However, drawbacks associated with this approach are usually under-estimated. RESULTS: We have carried out simulations by using a recently published High Osmolarity Glycerol (HOG) pathway from S.cerevisiae to demonstrate these drawbacks. We have shown that it is very important how the data is partitioned and which part of the data is used for validation purposes. The hold-out validation strategy leads to biased conclusions, since it can lead to different validation and selection decisions when different partitioning schemes are used. Furthermore, finding sensible partitioning schemes that would lead to reliable decisions are heavily dependent on the biology and unknown model parameters which turns the problem into a paradox. This brings the need for alternative validation approaches that offer flexible partitioning of the data. For this purpose, we have introduced a stratified random cross-validation (SRCV) approach that successfully overcomes these limitations. CONCLUSIONS: SRCV leads to more stable decisions for both validation and selection which are not biased by underlying biological phenomena. Furthermore, it is less dependent on the specific noise realization in the data. Therefore, it proves to be a promising alternative to the standard hold-out validation strategy. PMID- 26152207 TI - Gastroprotective and ulcer healing effects of Piptadeniastrum Africanum on experimentally induced gastric ulcers in rats. AB - BACKGROUND: Gastric peptic ulcer is one of the common disorders of gastrointestinal tract, which occur due to an imbalance between the offensive and defensive factors. It is an illness that affects a considerable number of people worldwide. This study was conducted to evaluate the antiulcerogenic and antiulcer effects and recognize the basic mechanism of action of Piptadeniastrum africanum stem bark extracts. METHODS: The aqueous and methanol extracts of Piptadeniastrum africanum were administered at the doses 125, 250 and 500 mg/kg to evaluate their effects on gastric ulcer induced by the HCl/ethanol mixture, indomethacin and acetic acid in Wistar strain male adult rats, aged between 12 and 16 weeks and weighing between 180 and 220 g. Ranitidine, Maalox and Misoprostol were used as standard drugs. Histopathological examination and nitric oxide level were performed to evaluate the basic mechanism of action of Piptadeniastrum africanum. Phytochemical screening was carried out to identify known phytochemicals present in these extracts. RESULTS: The aqueous and methanol extracts of stem bark of Piptadeniastrum africanum significantly inhibited (p < 0.01) gastric ulceration induced by HCl/ethanol to the percentages of inhibition of 81.38; 98.75 and 100 % for the aqueous extract and then 75.83, 89.76 and 96.52 % for the methanol extract, and with the Indomethacin-induced ulcers, aqueous and methanol extracts of bark of Piptadeniastrum africanum reduce significantly (p < 0.01) induced gastric lesions in rats, with percentage of cure 35.75; 52.33 and 98.58 % for the aqueous extract, and 33.7; 51.97; and 65.93 to the methanol extract. The results revealed a significant reduction of ulcerated surface in both extracts and increase of nitric oxide (NO) level with methanol extract. When compared to methanol extract, aqueous extract showed more pronounced effects, corresponding to percentages of healing of 59. 92; 84.12 and 59.65 % for the aqueous extract; and 70.43; 55.49 and 57.59 % for the methanol extract in the ulcer induced by acetic acid, all at the respective doses of 125, 250 and 500 mg/kg. Histopathological observations also demonstrated curative effect. As such, both extracts were found to exhibit preventive and curative effects through the release of NO and growth factors. This could also be due to the presence of phytochemicals such as alkaloids, flavonoids, phenols and saponins which act as antisecretory agents. CONCLUSIONS: Piptadeniastrum africanum stem bark extracts thus have gastroprotective and ulcer healing effects, which could result from their activities by stimulating important cellular mechanisms such as migration and proliferation of epithelial cells that may have a cytoprotective effect by stimulating the release of prostaglandins. These results are required to confirm the ethnopharmacological use of Piptadeniastrum africanum stem bark in the treatment of ulcer. PMID- 26152208 TI - Industry paid $6.5 bn to US physicians and hospitals in 2014. PMID- 26152209 TI - Carica papaya induces in vitro thrombopoietic cytokines secretion by mesenchymal stem cells and haematopoietic cells. AB - BACKGROUND: Use of Carica papaya leaf extracts, reported to improve thrombocyte counts in dengue patients, demands further analysis on the underlying mechanism of its thrombopoietic cytokines induction METHODS: In vitro cultures of peripheral blood leukocytes (PBL) and stem cells from human exfoliated deciduous teeth (SHED) were treated with unripe papaya pulp juice (UPJ) to evaluate its potential to induce thrombopoietic cytokines (IL-6 and SCF) RESULTS: In vitro scratch gap closure was significantly faster (p < .05) in SHED culture treated with UPJ. IL-6 concentration was significantly increased (p < .05) in SHED and PBL culture supernatant when treated with UPJ. SCF synthesis in SHED culture was also significantly increased (p < .05) when treated with UPJ CONCLUSION: In vitro upregulated synthesis of IL -6 and SCF both in PBL and SHED reveals the potential mechanism of unripe papaya to induce thrombopoietic cytokines synthesis in cells of hematopoietic and mesenchymal origin. PMID- 26152210 TI - Direct differentiation of herbal medicine for volatile components by a multicapillary column with ion mobility spectrometry method. AB - In this work, a headspace system coupled to a gas chromatographic column and ion mobility spectrometry was applied as a screening system to differentiate the crude and processed "atractylodis macrocephalae rhizoma" samples. The obtained ion mobility data were consecutively processed by principal component analysis and Radar fingerprint chart methods. From the principal component analysis for the initial solution to original variables, the two principal components accounted for 68 and 13% of the total variance, respectively. The established method was proven to be valuable for classification, discrimination between herbal medicines from different processing procedures. PMID- 26152211 TI - Effect of Ampelopsis Radix on wound healing in scalded rats. AB - BACKGROUND: Ampelopsis Radix has been used as a traditional Korean medicine for the treatment of burns and scalds. However, there has been no scientific research to date on the wound healing properties of Ampelopsis Radix for scald burns. This study aimed to evaluate the healing effect of Ampelopsis japonica root tuber ethanol extract (AJE) on induced cutaneous scald injury in Sprague Dawley (SD) rats. METHODS: Hot water scalds were induced in SD rats, who were then divided into the following 5 groups; 1) control group without treatment, 2) positive control group with 1% Silver sulfadiazine (SSD), 3) Vaseline group, and groups 4) and 5) that used Vaseline containing 5% and 20% AJE, respectively. The ointment was applied topically to the experimental rats, once daily for 21 days, starting at 24 h post induction of the scald injury. Gross examination, measurement of wound size, and histopathological examination were performed. And quantitative measurement of cytokine levels of tumor necrosis factor alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor beta 1 (TGF-beta1), and vascular endothelial growth factor (VEGF) were performed by enzyme-linked immunosorbent assay. RESULTS: Clinical evaluation showed that the AJE and Vaseline groups, rapidly desquamated scab on day 12 post-scalding; in particular, the 20% AJE group achieved the greatest extent of skin recovery. Sizes of scald wound were significantly lower on days 12, 15, 18, and 21 in the AJE treated groups compared to the control groups. Histopathological evaluation showed a well organized epithelial layer, angiogenesis, tissue granulation and collagen formation with the exception of inflammatory cells in the AJE-treated groups compared to the control groups on day 14, indicating that tissue regeneration had occurred. AJE treatment decreased TNF-alpha and increased IL-10 levels on days 2 and 14, indicating the anti-inflammatory action of AJE. The AJE groups also showed a decrease in TGF-beta1 levels on day 7 and VEGF on day 14 in the serum of scald inflicted SD rat model. CONCLUSIONS: These results suggest that AJE possesses scald wound healing activity via accelerating the scald wound repair during the inflammation and proliferative phases of the healing process. PMID- 26152213 TI - Local cluster symmetry of a highly ordered quasicrystalline Al58Cu26Ir16 extracted through multivariate analysis of STEM images. AB - The structure of a highly ordered Al58Cu26Ir16 decagonal quasicrystal (d-QC), which is constructed by a periodic stack of quasiperiodic atomic planes, was investigated using aberration-corrected scanning transmission electron microscopy. The entire quasiperiodic structure can be well described based on the pentagonal Penrose lattice decorated with a decagonal columnar cluster 2 nm across, and the individual clusters apparently showed up with localized atomic disorder to various degree that blurs the underlying cluster symmetry. Multivariate analysis of the cluster images with principal component analysis has successfully extracted two fundamental clusters, which are with definite mirror and 10-fold-rotation symmetries; this is the first solid example of the d-QC composed of multiple fundamental clusters with different symmetry. Consequently, it is found that all the observed variations can be reasonably interpreted by a linear combination between these two fundamental clusters of mirror and 10-fold symmetries, indicating that the possible atomic disorder is strongly restricted by these particular symmetries. Characteristic distributions of the mirror/10 fold clusters on the pentagonal Penrose lattice are also described. PMID- 26152214 TI - STED microscopy--super-resolution bio-imaging utilizing a stimulated emission depletion. AB - One of the most popular super-resolution microscopies that breaks the diffraction barrier is stimulated emission depletion (STED) microscopy. As the optical set-up of STED microscopy is based on a laser scanning microscopy (LSM) system, it potentially has several merits of LSM like confocal or two-photon excitation LSM. In this article, we first describe the principles of STED microscopy and then describe the features of our newly developed two-photon excitation STED microscopy. On the basis of our recent results and those of other researchers, we conclude by discussing future research and new technologies in this field. PMID- 26152212 TI - Structural basis of blocking integrin activation and deactivation for anti inflammation. AB - Integrins mediate leukocyte accumulation to the sites of inflammation, thereby enhancing their potential as an important therapeutic target for inflammatory disorders. Integrin activation triggered by inflammatory mediators or signaling pathway is a key step to initiate leukocyte migration to inflamed tissues; however, an appropriately regulated integrin deactivation is indispensable for maintaining productive leukocyte migration. While typical integrin antagonists that block integrin activation target the initiation of leukocyte migration, a novel class of experimental compounds has been designed to block integrin deactivation, thereby perturbing the progression of cell migration. Current review discusses the mechanisms by which integrin is activated and subsequently deactivated by focusing on its structure-function relationship. PMID- 26152215 TI - A guide to use photocontrollable fluorescent proteins and synthetic smart fluorophores for nanoscopy. AB - Recent advances in nanoscopy, which breaks the diffraction barrier and can visualize structures smaller than the diffraction limit in cells, have encouraged biologists to investigate cellular processes at molecular resolution. Since nanoscopy depends not only on special optics but also on 'smart' photophysical properties of photocontrollable fluorescent probes, including photoactivatability, photoswitchability and repeated blinking, it is important for biologists to understand the advantages and disadvantages of fluorescent probes and to choose appropriate ones for their specific requirements. Here, we summarize the characteristics of currently available fluorescent probes based on both proteins and synthetic compounds applicable to nanoscopy and provide a guideline for selecting optimal probes for specific applications. PMID- 26152216 TI - Normal lower limb variants in children. PMID- 26152217 TI - Relationship between environment factors and the number of outpatient visits at a clinic for nonallergic rhinitis in Japan, extracted from electronic medical records. AB - BACKGROUND: The objective of this study was to evaluate the influence of the environmental factors (meteorological factors, air pollutant levels, etc.) on the number of clinic consultations for nonallergic rhinitis (NAR). METHODS: Among the 9056 outpatients visiting a general internal medicine clinic in Japan between August 2012 and the end of July 2013 (counting return visitors as multiple cases), the total daily number of first visits for NAR plus the number of extraordinary visits by patients with NAR for acute exacerbation of the disease was investigated using electronic medical records and analyzed. RESULTS: Major parameters with significant Spearman's correlation coefficients and significant correlation coefficients also in the multiple regression analysis were the mean vapor pressure (coefficient of determination 27.3 %) throughout the year, mean vapor pressure (58.4 %), mean temperature (44.4 %), maximum 10-min precipitation (12.0 %) only during the autumn-winter period, and temperature difference (13.3 %) only during the spring-summer period. CONCLUSIONS: The mean vapor pressure is the most important environmental factor associated with acute exacerbation of NAR. PMID- 26152218 TI - Haloperidol dose combined with dexamethasone for PONV prophylaxis in high-risk patients undergoing gynecological laparoscopic surgery: a prospective, randomized, double-blind, dose-response and placebo-controlled study. AB - BACKGROUND: Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. METHODS: Female adults (n = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0-2 h) and late (2-24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). RESULTS: The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; P = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (P < 0.001). CONCLUSIONS: For high-risk PONV patients undergoing gynecological laparoscopic surgery, when used with dexamethasone, 1-mg haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01639599 ). PMID- 26152219 TI - A Republican Egalitarian Approach to Bioethics: The Case of the Unrecognized Bedouin Villages in Israel. AB - This article argues that current, mainstream, liberal approaches to the right to health and to bioethics are not adequately aware of the structural and political character of health and illness. We propose a radical egalitarian definition of the right to health as the basis for the discussion of a republican egalitarian perspective on bioethics that redefines autonomy and stresses the importance of equality, political participation, and the common good. The violations of the right to health in unrecognized Bedouin villages in Israel are analyzed to exemplify the possibilities opened by the republican egalitarian approach. PMID- 26152220 TI - Utilization of and Adherence to Oral Contraceptive Pills and Associated Disparities in the United States: A Baseline Assessment for the Impact of the Affordable Care Act of 2010. AB - This study investigated sociological factors that may influence women's utilization of and adherence to oral contraceptive pills. This was a retrospective cross-sectional study using the 2010-2012 Medical Expenditure Panel Survey. Female adults aged 18-50 years were included. Logistic regression was performed to discern women's decisions to use oral contraceptive pills or not. Ordinary least squares and Poisson regressions were conducted to examine the number of oral contraceptive pills received, refill frequency, and annual out-of pocket expenditure on oral contraceptive pills. Covariates were based on the Andersen model of health care utilization. Among the study sample (weighted n = 207,007,531), 14.8% were oral contraceptive pill users. Factors positively related to oral contraceptive pill use included non-Hispanic white ethnicity, younger age, not currently married, having private insurance, residing in the Midwest, higher education level, and higher annual family income. Being non Hispanic white and having a higher education level were positively related to oral contraceptive pill adherence. Our findings therefore demonstrate disparities in oral contraceptive pill utilization and adherence, especially according to women's race/ethnicity and educational level. This study serves as a baseline assessment for the impact of the Affordable Care Act on oral contraceptive pill utilization and adherence for future studies. PMID- 26152222 TI - Diagnosis and surgical treatment for isolated tricuspid Libman-Sacks endocarditis: a rare case report and literatures review. AB - Libman-Sacks endocarditis (LSE), characterized by verrucous vegetations formation, is a typical cardiac manifestation of autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It primarily leads to lesions of cardiac valves and mostly involved valves are mitral and aortic, but isolated tricuspid valve involvement is exceptional. Here we reported a 20-years-old female with past SLE history suffered from acute right heart failure caused by multiple tricuspid vegetations and valve regurgitation. The patient recovered following tricuspid valve replacement with a bioprosthesis. Transesophageal echocardiography(TEE), especially real time 3-dimensional (RT3D) TEE provide a better imaging modality for assessing cardiac valvular involvement of LSE. For patients with active SLE/APS course, uncontrolled systemic inflammation may made it difficult for surgical exposure and suture. The durability of bioprosthesis for this patient and the prosthesis selection for tricuspid LSE both need further follow-up and more clinical investigation. PMID- 26152221 TI - Influence of glycemic control on gain in VO2 peak, in patients with type 2 diabetes enrolled in cardiac rehabilitation after an acute coronary syndrome. The prospective DARE study. AB - BACKGROUND: Gain in VO2 peak after cardiac rehabilitation (CR) following an acute coronary syndrome (ACS), is associated with reduced mortality and morbidity. We have previously shown in CR, that gain in VO2 peak is reduced in Type 2 diabetic patients and that response to CR is impaired by hyperglycemia. METHODS: We set up a prospective multicenter study (DARE) whose primary objective was to determine whether good glycemic control during CR may improve the gain in VO2 peak. Sixty four type 2 diabetic patients, referred to CR after a recent ACS, were randomized to insulin intensive therapy or a control group with continuation of the pre-CR antidiabetic treatment. The primary objective was to study the effect of glycemic control during CR on the improvement of peak VO2 by comparing first the 2 treatment groups (insulin intensive vs. control) and second, 2 pre-specified glycemic control groups according to the final fructosamine level (below and above the median). RESULTS: At the end of the CR program, the gain in VO2 peak and the final fructosamine level (assessing glycemic level during CR) were not different between the 2 treatment groups. However, patients who had final fructosamine level below the median value, assessing good glycemic control during CR, showed significantly higher gain in VO2 peak (3.5 +/- 2.4 vs. 1.7 +/- 2.4 ml/kg/min,p = 0.014) and ventilatory threshold (2.7 +/- 2.5 vs. 1.2 +/- 1.9 ml/kg/min,p = 0.04) and a higher proportion of good CR-responders (relative gain in VO2 peak >= 16 %): 66 % vs. 36 %, p = 0.011. In multivariate analysis, gain in VO2 peak was associated with final fructosamine level (p = 0.010) but not with age, gender, duration of diabetes, type of ACS, insulin treatment or basal fructosamine. CONCLUSIONS: The DARE study shows that, in type 2 diabetes, good glycemic control during CR is an independent factor associated with gain in VO2 peak. This emphasizes the need for good glycemic control in CR for type 2 diabetic patients. TRIAL REGISTRATION: Trial registered as NCT00354237 (19 July 2006). PMID- 26152223 TI - Direct and indirect determinants of childhood malaria morbidity in Malawi: a survey cross-sectional analysis based on malaria indicator survey data for 2012. AB - BACKGROUND: Children under the age of five are most vulnerable to malaria (malaria is a major health challenge in sub-Saharan Africa) with a child dying every 30 s from malaria. Hampered socio-economic development, poverty, diseconomies of scale, marginalization, and exploitation are associated with malaria. Therefore establishing determinants of malaria in affected sub-Saharan populations is important in order to come up with informed interventions that will be effective in malaria control. METHODS: The study was a cross-sectional survey design based on data from the Malawi 2012 Malaria indicator Survey obtained from Demographic and Health Survey (DHS) programme website. The outcome variable was positive laboratory-based blood smear result for malaria in children less than 5 years, after an initial positive rapid malaria diagnostic test done at the homestead. Statistical modelling was done using survey logistic regression as well as generalized structural equation modelling (G-SEM) to analyse direct and indirect effects of malaria. RESULTS: The propensity score matched data had 1 325 children with 367 (27.7%) having blood smear positive malaria. Female children made up approximately 53% of the total study participants. Child related variables (age, haemoglobin and position in household) and household wealth index were significant directly and indirectly. Further on G-SEM based multivariable analysis showed socio-economic status (SES) [Odds ratio (OR) = 0.96, 95% Confidence interval (CI) = 0.92, 0.99] and primary level of education [OR = 0.50, 95% CI = 0.32, 0.77] were important direct and indirect determinants of malaria morbidity. CONCLUSION: Socio-economic status and education are important factors that influence malaria control. These factors need to be taken into consideration when planning malaria control programmes in order to have effective programmes. Direct and indirect effect modelling can also provide an alternative modelling technique that incorporates surrogate confounders that may not be significant when modelled directly. This holistic approach is useful and will help in improving malaria control. PMID- 26152224 TI - Parallel phase 1 clinical trials in the US and in China: accelerating the test of avitinib in lung cancer as a novel inhibitor selectively targeting mutated EGFR and overcoming T790M-induced resistance. AB - Avitinib, a new generation inhibitor of epidermal growth factor receptor (EGFR), was approved for clinical trial in both China and the United States, and the phase 1 trials were initiated in both countries in parallel. In the preclinical studies, avitinib showed three novel features including (1) irreversibly binding EGFR by forming a covalent bound with Cys 797 in the ATP-binding pocket, (2) sparing wild-type EGFR, and (3) overcoming T790M-induced resistance. Avitinib is the first China-developed novel EGFR inhibitor that has entered in global clinical trials, and will provide a precision targeted therapy for non-small cell lung cancer patients. PMID- 26152225 TI - Photocurrent generation in lateral graphene p-n junction created by electron-beam irradiation. AB - Graphene has been considered as an attractive material for optoelectronic applications such as photodetectors owing to its extraordinary properties, e.g. broadband absorption and ultrahigh mobility. However, challenges still remain in fundamental and practical aspects of the conventional graphene photodetectors which normally rely on the photoconductive mode of operation which has the drawback of e.g. high dark current. Here, we demonstrated the photovoltaic mode operation in graphene p-n junctions fabricated by a simple but effective electron irradiation method that induces n-type doping in intrinsic p-type graphene. The physical mechanism of the junction formation is owing to the substrate gating effect caused by electron irradiation. Photoresponse was obtained for this type of photodetector because the photoexcited electron-hole pairs can be separated in the graphene p-n junction by the built-in potential. The fabricated graphene p-n junction photodetectors exhibit a high detectivity up to ~3 * 10(10) Jones (cm Hz(1/2) W(-1)) at room temperature, which is on a par with that of the traditional III-V photodetectors. The demonstrated novel and simple scheme for obtaining graphene p-n junctions can be used for other optoelectronic devices such as solar cells and be applied to other two dimensional materials based devices. PMID- 26152226 TI - Antigenotoxic effects of resveratrol: assessment of in vitro and in vivo response. AB - Experiments were performed to evaluate the in vitro and in vivo dose response for antigenotoxic effects of resveratrol (RES). For the in vitro study, HL-60 cells were co-treated with the test genotoxin and three concentrations of RES. Thereafter, genotoxic effects were assessed in the cytokinesis-block micronucleus test. Results of the in vitro experiments using genotoxins nitroquinoline-1-oxide (NQO) and mitomycin C (MMC) showed maximum inhibition of genotoxicity with the lowest test concentration of RES. The mouse bone marrow micronucleus assay was used for evaluating the in vivo antigenotoxic effects of RES against genotoxins diepoxybutane (DEB), MMC, methyl methanesulfonate and procarbazine (PCB). The experimental animals received RES pre-treatment by gavage 30min, 24 and 48h before injecting the genotoxin intraperitoneally. The in vivo studies demonstrated efficacy of the lowest test dose of RES for exerting maximum protection against chromosomal damage induced by all four genotoxins. The antigenotoxic effect observed with 6.25mg/kg RES was significantly higher than that of 100mg/kg RES against PCB and DEB. In conclusion, the findings from the present study indicate that lower test concentrations/doses of RES are more effective in exerting antigenotoxic effects. PMID- 26152227 TI - Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens. AB - Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino 3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2' deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment. PMID- 26152230 TI - Early-Phase Oncology Research Training (EFFORT) program: a Hengrui-USCACA joint scholarship. PMID- 26152228 TI - Prevention of Relapse and Recurrence in Adults with Major Depressive Disorder: Systematic Review and Meta-Analyses of Controlled Trials. AB - BACKGROUND: Findings of substantial remaining morbidity in treated major depressive disorder (MDD) led us to review controlled trials of treatments aimed at preventing early relapses or later recurrences in adults diagnosed with MDD to summarize available data and to guide further research. METHODS: Reports (n = 97) were identified through systematic, computerized literature searching up to February 2015. Treatment versus control outcomes were summarized by random effects meta-analyses. RESULTS: In 45 reports of 72 trials (n = 14 450 subjects) lasting 33.4 weeks, antidepressants were more effective than placebos in preventing relapses (response rates [RR] = 1.90, confidence interval [CI]: 1.73 2.08; NNT = 4.4; p < 0.0001). In 35 reports of 37 trials (n = 7253) lasting 27.0 months, antidepressants were effective in preventing recurrences (RR = 2.03, CI 1.80-2.28; NNT = 3.8; p < 0.0001), with minor differences among drug types. In 17 reports of 22 trials (n = 1 969) lasting 23.7 months, psychosocial interventions yielded inconsistent or inconclusive results. CONCLUSIONS: Despite evidence of the efficacy of drug treatment compared to placebos or other controls, the findings further underscore the substantial, unresolved morbidity in treated MDD patients and strongly encourage further evaluations of specific, improved individual and combination therapies (pharmacological and psychological) conducted over longer times, as well as identifying clinical predictors of positive or unfavorable responses and of intolerability of long-term treatments in MDD. PMID- 26152229 TI - Dietary flavonoid intake and cardiovascular risk: a population-based cohort study. AB - BACKGROUND: The cardio-protective effects of flavonoids are still controversial; many studies referred to the benefits of specific foods, such as soy, cocoa, tea. A population-based cohort of middle-aged adults, coming from a semi-rural area where the consumption of those foods is almost negligible, was studied. AIMS: The primary objective was establishing if flavonoid intake was inversely associated with the cardiovascular (CV) risk evaluated after 12-year follow-up; the associations between flavonoid intake and CV incidence and mortality and all cause mortality were also evaluated. METHODS: In 2001-2003, a cohort of 1,658 individuals completed a validated food-frequency questionnaire. Anthropometric, laboratory measurements, medical history and the vital status were collected at baseline and during 2014. The CV risk was estimated with the Framingham risk score. RESULTS: Individuals with the lowest tertile of flavonoid intake showed a worse metabolic pattern and less healthy lifestyle habits. The 2014 CV risk score and the increase in the risk score from baseline were significantly higher with the lowest intake of total and all subclasses of flavonoids, but isoflavones, in a multiple regression model. During follow-up, 125 CV events and 220 deaths (84 of which due to CV causes) occurred. CV non-fatal events were less frequent in individuals with higher flavonoid intake (HR = 0.64; 95%CI 0.42-1.00 and HR = 0.46; 95%CI 0.28-0.75 for the second and third tertiles, respectively) in Cox regression models, after multiple adjustments. All subclasses of flavonoids, but flavones and isoflavones, were inversely correlated with incident CV events, with HRs ranging from 0.42 (flavan-3-ols) to 0.56 (anthocyanidins). Being in the third tertile of flavan-3-ols (HR = 0.68; 95% CI 0.48-0.96), anthocyanidins (HR = 0.66; 95% CI 0.46-0.95) and flavanones (HR = 0.59; 95% CI 0.40-0.85) was inversely associated with all-cause mortality. Total and subclasses of flavonoids were not significantly associated with the risk of CV mortality. CONCLUSIONS: Flavonoid intake was inversely associated with CV risk, CV non-fatal events and all-cause mortality in a cohort with a low consumption of soy, tea and cocoa, which are typically viewed as the foods responsible for flavonoid-related benefits. PMID- 26152231 TI - Community-directed interventions are practical and effective in low-resource communities: experience of ivermectin treatment for onchocerciasis control in Cameroon and Uganda, 2004-2010. AB - BACKGROUND: The community-directed intervention (CDI) approach has improved treatment coverage in onchocerciasis-affected communities. However, there is still a lot to learn. This study assessed its performance and highlighted the lessons learnt so far. METHODS: Representative samples of households were selected from Cameroon and Uganda program areas through multi-stage random sampling. An adult male and female from every selected household were interviewed separately on their involvement in CDI activities every year between 2004 and 2010. Community health workers (CHWs) were interviewed and treatment records reviewed to determine whether 90% treatment coverage was attained within 2 weeks. Records related to training of CHWs and their supervisors were analyzed. RESULTS: Decision making decreased for community leaders and health workers, while it increased for community members. The proportion of CHWs attaining 90% treatment coverage within 2 weeks improved as their demand for monetary incentives, and number of persons they served, reduced. The number of CHWs supervised by a community supervisor remained low, but increased for the health workers. The cost of training a CHW and a community supervisor reduced to about US$1 and US$4.8, respectively. CONCLUSIONS: The CDI approach was effective, culturally appropriate and probably less costly in delivering health services in low-resource communities. PMID- 26152233 TI - Hearing loss is important in dementia. PMID- 26152234 TI - Amplatzer duct occluder II for closure of congenital Gerbode defects. AB - BACKGROUND: Congenital left ventricle to right atrial communications (Gerbode defects) are extremely rare (0.08%) type of ventricular septal defects. They were traditionally closed by surgery in the past. There are few case reports and small series of acquired and congenital Gerbode defects, closed with various types of devices. Aim of our study is to assess the feasibility, efficacy, and complications of transcatheter closure of congenital Gerbode defects with Amplatzer duct occluder II (ADO II). MATERIAL: Twelve consecutive cases of Gerbode defects, age ranging from 10 months to 16 years (mean 6.7 years), weight ranging from 6.5 kg to 34 kg (mean 19.3 kg), were diagnosed on transthoracic echocardiography. RESULTS: Transcatheter closure of Gerbode defects was done successfully through retrograde approach with ADO II. No aortic or tricuspid regurgitation or residual shunt occurred in any of the patients. One patient developed transient complete heart block needing temporary pacing. DISCUSSION: The soft low profile, easily trackable ADO II appears to be ideal for closure of Gerbode defects, as the central cylinder fits in the defect and the soft retention discs on either side, without polyester material, do not impinge on either aortic, mitral, or tricuspid valve. We report the successful transcatheter closure of twelve cases of congenital Gerbode defects with ADO II. CONCLUSIONS: Transcatheter closure of congenital Gerbode defects with ADO II is safe, effective, and an attractive alternative to surgical closure. ADO II appears to be tailor made for Gerbode defects, as the success rate is very high and complication rate is very low. PMID- 26152232 TI - Mesenchymal stromal cells for cutaneous wound healing in a rabbit model: pre clinical study applicable in the pediatric surgical setting. AB - OBJECTIVE: Mesenchymal stromal cells (MSCs) expanded in vitro have been proposed as a potential therapy for congenital or acquired skin defects in pediatrics. The aim of this pre-clinical study was to investigate the effects of intradermal injections of MSC in experimental cutaneous wound repair comparing allogeneic and autologous adipose stem cells (ASCs) and autologous bone marrow-mesenchymal stromal cells (BM-MSCs). METHODS: Mesenchymal stromal cells were in vitro expanded from adipose and BM tissues of young female New Zealand rabbits. MSCs were characterized for plastic adhesion, surface markers, proliferation and differentiation capacity. When an adequate number of cells (ASCs 10 * 10(6) and BM-MSCs 3 * 10(6), because of their low rate of proliferation) was reached, two skin wounds were surgically induced in each animal. The first was topically treated with cell infusions, the second was used as a control. The intradermal inoculation included autologous or allogeneic ASCs or autologous BM-MSCs. For histological examination, animals were sacrificed and wounds were harvested after 11 and 21 days of treatment. RESULTS: Rabbit ASCs were isolated and expanded in vitro with relative abundance, cells expressed typical surface markers (CD49e, CD90 and CD29). Topically, ASC inoculation provided more rapid wound healing than BM-MSCs and controls. Improved re-epithelization, reduced inflammatory infiltration and increased collagen deposition were observed in biopsies from wounds treated with ASCs, with the best result in the autologous setting. ASCs also improved restoration of skin architecture during wound healing. CONCLUSION: The use of ASCs may offer a promising solution to treat extended wounds. Pre clinical studies are however necessary to validate the best skin regeneration technique, which could be used in pediatric surgical translational research. PMID- 26152235 TI - Application of gas diffusion electrodes in bioelectrochemical syntheses and energy conversion. AB - Combining the advantages of biological components (e.g., reaction specificity, self-replication) and electrochemical techniques in bioelectrochemical systems offers the opportunity to develop novel efficient and sustainable processes for the production of a number of valuable products. The choice of electrode material has a great impact on the performance of bioelectrochemical systems. In addition to the redox process at the electrodes, interactions of biocatalysts with electrodes (e.g., enzyme denaturation or biofouling) need to be considered. In recent years, gas diffusion electrodes (GDEs) have proved to be very attractive electrodes for bioelectrochemical purposes. GDEs are porous electrodes, that posses a large three-phase boundary surface. At this interface, a solid catalyst supports the electrochemical reaction between gaseous and liquid phase. This mini review discusses the application of GDEs in microbial and enzymatic fuel cells, for microbial electrolysis, in biosensors and for electroenzymatic synthesis reactions. PMID- 26152236 TI - Dietary (-)-Epigallocatechin-3-gallate Supplementation Counteracts Aging Associated Skeletal Muscle Insulin Resistance and Fatty Liver in Senescence Accelerated Mouse. AB - Aging is accompanied by pathophysiological changes including insulin resistance and fatty liver. Dietary supplementation with (-)-epigallocatechin-3-gallate (EGCG) improves insulin sensitivity and attenuates fatty liver disease. We hypothesized that EGCG could effectively modulate aging-associated changes in glucose and lipid metabolism in senescence-accelerated mice (SAM) prone 8 (SAMP8). Higher levels of glucose, insulin, and free fatty acid, inhibited Akt activity, and decreased glucose transporter 4 (GLUT4) expression were observed in SAMP8 mice compared to the normal aging group, SAM resistant 1 mice. EGCG supplementation for 12 weeks successfully decreased blood glucose and insulin levels via restoring Akt activity and GLUT4 expression and stimulating AMPKalpha activation in skeletal muscle. EGCG up-regulated genes involved in mitochondrial biogenesis and subsequently restored mitochondrial DNA copy number in skeletal muscle of SAMP8 mice. Decreased adipose triglyceride lipase and increased sterol regulatory element binding proteins-1c (SREBP-1c) and carbohydrate responsive element binding protein at mRNA levels were observed in SAMP8 mice in accordance with hepatocellular ballooning and excess lipid accumulation. The pevention of hepatic lipid accumulation by EGCG was mainly attributed to down-regulation of mTOR and SREBP-1c-mediated lipid biosynthesis via suppression of the positive regulator, Akt, and activation of the negative regulator, AMPKalpha, in the liver. EGCG beneficially modulates glucose and lipid homeostasis in skeletal muscle and liver, leading to alleviation of aging-associated metabolic disorders. PMID- 26152238 TI - Case-report: endovascular treatment of aortic pseudo-aneurysm caused by Fishbone. AB - Aortic pseudo-aneurysm (APA) is a rare disease in clinic. Because of its relative rarity, we are far from making any conclusion regarding the natural history and appropriate therapeutic strategy for this condition. This study is to investigate the treatment effect of interventional therapy in aortic pseudo-aneurysm. A woman of 68 years old diagnosed with APA caused by fishbone was treated with stent grafts. After treatment, the therapeutic effect was assessed by measuring the size of trauma. The patient recovered well after stent grafts treatment, as her trauma was minimal. However, some complications of intravascular interventional treatment were observed. Compared with conventional surgery, interventional therapy of intravascular stent grafts has its merits. Therefore, this strategy was worthy to apply in the treatment of aortic pseudo-aneurysm. PMID- 26152237 TI - HBV genotypes and response to tenofovir disoproxil fumarate in HIV/HBV-coinfected persons. AB - BACKGROUND: Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood. METHODS: HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA <20 IU/mL) and the influence of HBV genotypes were determined. RESULTS: 143 HIV/HBV-coinfected participants with detectable HBV DNA were identified. The predominant HBV genotypes were A (82 patients, 57 %); and D (35 patients, 24 %); 20 patients (14 %) were infected with multiple genotypes (3 % A + D and 11 % A + G); and genotypes B, C and E were each present in two patients (1 %). TDF completely suppressed HBV DNA in 131 patients (92 %) within 6 months; and in 12 patients (8 %), HBV DNA suppression was delayed. No HBV resistance mutations to TDF were found in patients with delayed response, but all were infected with HBV genotype A (among these, 5 patients with genotype A + G), and all had previously been exposed to lamivudine. CONCLUSION: In HIV/HBV-coinfected patients, infection with multiple HBV genotypes was more frequent than previously reported. The large majority of patients had an undetectable HBV viral load at six months of TDF containing ART. In patients without viral suppression, no TDF-related resistance mutations were found. The role of specific genotypes and prior lamivudine treatment in the delayed response to TDF warrant further investigation. PMID- 26152239 TI - Progression of chromosomal damage induced by etoposide in G2 phase in a DNA-PKcs deficient context. AB - Etoposide (ETO), a drug used for the treatment of human tumors, is associated with the development of secondary malignancies. Recently, therapeutic strategies have incorporated chemosensitizing agents to improve the tumoral response to this drug. ETO creates DNA double-strand breaks (DSB) via inhibition of DNA topoisomerase II (Top2). To repair DSB, homologous recombination (HR) and non homologous end-joining (NHEJ), involving D-NHEJ (dependent of the catalytic subunit of DNA-dependent protein kinase, DNA-PKcs) and B-NHEJ (backup repair pathway) are activated. We evaluated the progression of the DNA damage induced by the Top2 poison ETO in G2 phase of human HeLa cells after chemical inhibition of DNA-PKcs with NU7026. Compared to ETO treatment alone, this combined treatment resulted in a twofold higher rate of chromatid breaks and exchanges when analysis was performed in the following metaphase. Moreover, when analysis was performed in the second metaphase following treatment, increases in the percentage of micronuclei with H2AX (biomarker for DSB) foci in binucleated cells and dicentric chromosomes were seen. In post-mitotic G1 phase, a close association between unresolved DSB and meiotic recombination 11 homolog A (MRE11) signals was observed, demonstrating the contribution of MRE11 in the DSB repair by B-NHEJ. Hence, chemical inhibition of DNA-PKcs impaired both D-NHEJ and HR repair pathways, altering the maintenance of chromosomal integrity and cell proliferation. Our results suggest that the chemosensitizing effectiveness of the DNA-PKcs inhibitor and the survival rate of aberrant cells may contribute to the development of therapy-related tumors. PMID- 26152240 TI - Reduction and internal fixation of displaced intra-articular calcaneal fractures with a locking nail: a prospective study of sixty nine cases. AB - PURPOSE: The best treatment for intra-articular fractures of the calcaneus is still debated. The aims of this study were to determine whether intrafocal reduction of thalamic fractures is effective, to evaluate whether a locking nail is able to maintain reduction of the articular surface and to analyse the functional results of this original method. METHODS: This prospective study assessed 69 fractures treated with a locking fracture nail in 63 cases and with primary subtalar fusion in six (Calcanail ((r)), FH). Articular congruity and global reduction of the calcaneus was assessed in all patients by computed tomography (CT) scan three months postoperatively. Functional results were evaluated according to the American Orthopaedic Foot and Ankle Society Ankle Hindfoot Score (AOFAS-AHS) and all complications recorded. RESULTS: For the 63 fracture nails, the average AOFAS score was 85.9 at a mean final follow-up of 12 months. Only three secondary fusions were performed. For the six comminuted fractures requiring primary fusion, the average AOFAS score was 75.9 at the last follow-up. CONCLUSIONS: The posterior intrafocal approach for both reduction and locked nailing of intra-articular calcaneal fractures has been proven as an effective and reliable procedure. PMID- 26152241 TI - Attitudes of Nigerian orthopaedic surgeons to the use of prophylactic antibiotics. AB - PURPOSE: Inappropriate use of prophylactic antibiotics can increase the rates of surgical site wound infections, lead to the development of resistant organisms and to increased health care costs. Despite widespread knowledge of standard antibiotic prophylaxis protocols (SAPs) in implant surgeries, it is thought that many Nigerian surgeons do not comply. The purpose of this study was to determine the awareness of Nigerian orthopaedic surgeons of SAPs in implant surgeries and their compliance. METHODS: This was an observational study done using a questionnaire to collect data from orthopaedic surgeons at the National Orthopaedic Association annual conference held at Lokoja, Nigeria in November 2013. RESULTS: There were 66 respondents divided into 56 consultants and ten surgical residents. Most respondents were aware of standard guidelines for the use of prophylactic antibiotics (86.36 %). Many of them (63.63 %) did not know the average rate of infection following implant surgery in their institutions. Compliance with SAPs was found to be 30.3 %. Compliance was worse among surgeons between 41 and 50 years of age and consultants with between six and ten years of practice. CONCLUSIONS: Most respondents are aware of standard antibiotic protocols, but do not comply with them. The study also suggests that surgeons with intermediate levels of experience and those between 41 and 50 years of age were most unlikely to comply. PMID- 26152242 TI - Hand-held navigation may improve accuracy in minimally invasive total knee arthroplasty: a prospective randomized controlled trial. AB - INTRODUCTION: A novel hand-held navigation combines gyroscopes, accelerometers and a secure local wireless channel to guide the distal femoral and proximal tibial cutting positions by displaying to the surgeon directly on the pods within the surgical field. No previous study has reported on its accuracy. MATERIALS AND METHODS: A prospective randomized controlled trial was performed to compare radiographic outcomes in minimally invasive surgery total knee arthroplasty (MIS TKA) with (40 patients, 40 knees) and without (40 patients, 40 knees) the novel hand-held navigation. RESULTS: The use of hand-held navigation resulted in fewer outliers (> +/- 3 degrees malalignment) in all frontal alignment: the hip-knee ankle, the femoral component, and the tibial component. Tibial slope was also better achieved with the navigation. Femoral component flexion was not significantly different. Operation time and bone cutting time with the navigation were not longer than those without. Blood loss from drainage was not significantly different. CONCLUSION: The hand-held navigation improves accuracy for mechanical alignment and positioning of the prosthesis without additional surgical time. PMID- 26152243 TI - The pathology of the anterior capsule in patients over forty years of age with recurrent shoulder dislocation. AB - PURPOSE: We evaluated the pathologies of anterior capsular mechanism in older patients with recurrent anterior shoulder dislocation in the absence of full thickness rotator cuff tears. METHODS: Three hundred and ninety-five shoulders with recurrent anterior shoulder dislocation were assessed. The patients were divided into three groups by the age at the first dislocation and the surgical treatment: group A (onset and treatment were at an age over 40 years), group B (onset was at an age under 40 years and treatment was at an age over 40 years) and group C (onset and treatment were at an age under 40 years). Groups A, B and C involved nine, 31 and 355 shoulders, respectively. RESULTS: The prevalence of an isolated Bankart lesion was 81.7 % in group C, 33.3 % in group A and 64.5 % in group B, and each of A and B was significantly lower than group C. The prevalence of an isolated capsular tear was 3.1 % in group C, while it was 33.3 % in group A, which was significantly higher. CONCLUSIONS: The prevalence of an isolated Bankart lesion was low and the prevalence of a capsular tear was high in older patients. We should keep in mind the existence of a capsular tear in older patients and examine the whole anterior capsular mechanism meticulously. PMID- 26152244 TI - Our experience in the management of segmental bone defects caused by gunshots. AB - PURPOSE: Bone and soft-tissue defects in the leg can be caused by high-energy trauma. One of the causes of extensive bone defects are gunshot injuries. The incidence of these has been noticeably increasing in recent years in countries with political instabilities due to the random availability of weapons. The aim of this study is to focus on the essentials of treatment of post-gunshot tibial bone loss using the Ilizarov concept. METHODS: In the period between June 2011 and July 2013, 30 patients with open tibial fractures after gunshots comprised the present study with an average follow-up of 18 months. The bone defect was associated with soft-tissue loss in 18 cases. All cases were subjected to extensive debridement of all devitalized tissues back to the healthy bone with viable soft tissue coverage. All cases were treated by the Ilizarov external fixator using the bifocal bone transport technique. RESULTS: The overall bone results were satisfactory in 28 cases (93.3 %). The overall functional results were satisfactory in 22 cases (73.3 %). The bone end results were significantly affected by age and smoking, while the functional end results were significantly affected by smoking, the presence of infection at the time of presentation, and complications during the procedure. CONCLUSIONS: Bone transport is a reliable method in the treatment of gunshot bone defects of the tibia after extensive debridement of all the devitalized tissues. The Ilizarov external fixator allows the functional use of the limb throughout the course of treatment, preventing disuse osteoporosis and increasing patient satisfaction. PMID- 26152245 TI - High failure rate of a new pressfit cup in mid-term follow-up. AB - BACKGROUND: Unacceptably high rates of loosening of a novel cementless cup system (Mathys, SeleXys TH+) have been reported. In this study, our mid-term-results with the SeleXys TH+ cup are compared with an established pressfit cup (Ceraver, Cerafit-R). METHODS: Between 2008 and 2011, a total of 407 implantations, 19 of them bilaterally, were conducted on 388 patients with the implants in question. A total of 280 cups were available for follow-up. Of these, 160 SeleXys TH+ cups and 120 Cerafit-R cups had been used. RESULTS: The mean follow-up period was 48.6 months (min. 28, max. 75). A total of 18 cases of loosening were found in the SeleXys TH+ group. Of these, one was of a traumatic nature and one was of septic origin. This left 16 cases of aseptic, atraumatic loosening (10% loosening rate). In the Cerafit-R group, only two cases (1.7%) of loosening were seen over the same period. Both were of traumatic origin. No cases of aseptic, atraumatic loosening were seen in the follow-up period. Further, significantly more cases of loosening were observed in women than in men with the SeleXys cup. CONCLUSIONS: The SeleXys TH+ cup shows an unacceptably high failure rate after six years. The time of revision is not limited to the first months after implantation, which means that close clinical and radiological controls will continue to be necessary in future in patients treated with SeleXys TH+ cups. Level of Evidenve: III (retrospective cohort study). PMID- 26152247 TI - Letter regarding article by Zhu et al.: management of the mid-shaft clavicle fractures using plate fixation versus intramedullary fixation: an updated meta analysis. PMID- 26152246 TI - Fall-induced fractures of the calcaneus and foot in older people: nationwide statistics in Finland between 1970 and 2013 and prediction for the future. AB - BACKGROUND: Although fall-induced fractures of elderly persons are a major problem, epidemiologic knowledge on their time trends is limited. We assessed the trends in fall-induced fractures of the calcaneus and foot in older Finns between 1970 and 2013. METHODS: The current trends in the number and incidence (per 100,000 persons) of fall-induced fractures of the calcaneus and foot of older Finns were determined by taking into account individuals 50-year-olds or older who were admitted to Finnish hospitals for primary treatment of such injury in 1970-2013. RESULTS: The number and raw incidence of these fractures increased considerably between 1970 and 2013, from 64 (number) and 5.6 (incidence) in 1970, to 325 and 15.0, respectively, in 2013. The age-adjusted incidence of fracture was higher in men than women and showed a clear rise in both sexes in 1970-2013, from 7.2 to 15.2 in men (111% increase), and from 4.3 to 13.9 in women (223% increase). A similar rise was observed in the age-specific incidences. If trends in the age-specific fracture incidence continue at the same rate as were observed in 1970-2013, and the 50-year-old or older population increases as predicted (by 15% by the year 2030), the annual number of fall-induced fractures of the calcaneus and foot in this population will be 1.8 times higher in the year 2030 (580 fractures) than it was in 2013 (325 fractures). CONCLUSIONS: The number of fall-induced fractures of the calcaneus and foot among Finns 50 years of age or older has risen sharply between 1970 and 2013 with a rate that cannot be explained merely by demographic changes. Further studies should examine the reasons for the rise and possibilities for fracture prevention. PMID- 26152248 TI - A comparative study between multiple cannulated screws and dynamic hip screw for fixation of femoral neck fracture in adults. AB - PURPOSE: In younger adults with fractures of the femoral neck, anatomic reduction is compulsory and maintaining the reduction is crucial. Both cannulated screws and dynamic hip screw (DHS) have the capacity of compression in the fracture site but the strength for keeping reduction is not the same. The aim of this study was to compare the results with fixations of the femoral neck fractures with cannulated screws versus dynamic hip screw. METHODS: This is a randomized clinical trial study on 58 cases with a minimum of one year follow-up. Leg length discrepancy, Harris Hip Score, infection, avascular necrosis of femoral head, and union of the fracture site were evaluated. RESULTS: There were two failures in the first trimester in the cannulated screw group and three more failures in the second and third trimesters in this group. In the DHS group, there was no reduction and fixation failure in the follow-up period. There was no fixation failure (0 %) in Group B (DHS) but there were five fixation failures (18 %) in Group A (screw), and there is significant difference between the groups (p < 0.001). The rate of avascular necrosis was the same in both groups. CONCLUSIONS: It seems to us that in our practice the fixation of femoral neck fracture in young adults with the DHS is a better option compared with the osteosynthsis with multiple cannulated screws. PMID- 26152249 TI - ATLS: Archaic Trauma Life Support? PMID- 26152250 TI - Training and assessment of non-technical skills in the operating theatre: where next? PMID- 26152251 TI - Peri-operative cessation of smoking: time for anaesthetists to act. PMID- 26152252 TI - Evaluation of the prototype Anaesthetic Non-technical Skills for Anaesthetic Practitioners (ANTS-AP) system: a behavioural rating system to assess the non technical skills used by staff assisting the anaesthetist. AB - This study tested the reliability, validity and usability of a prototype behavioural rating system for the non-technical skills of assistants working with the anaesthetist. Anaesthetic nurses and operating department practitioners (n = 48) used the prototype Anaesthetic Non-technical Skills for Anaesthetic Practitioners (ANTS-AP) system to rate the non-technical skills of anaesthetic assistants in 12 videos of simulated theatre work. Test-retest reliability was assessed with a sub-sample (n = 12). The skill categories assessed were 'situation awareness', 'teamwork and communication' and 'task management'. The internal consistency for the ratings of elements in categories was acceptable (Cronbach's alpha of 0.78, 0.77 and 0.69, respectively), with more modest inter rater reliability (intraclass correlations for categories 0.54, 0.70, 0.86), test retest reliability (intraclass correlations 0.68, 0.58, 0.38) and accuracy (weighted kappa 0.39). Most participants considered the system complete (n = 42, 87%), the wording clear (n = 48, 100%) and the system useful for structuring observation (n = 48, 100%). PMID- 26152253 TI - iCoplanin. PMID- 26152254 TI - Collecting safety data on procedural sedation. PMID- 26152255 TI - Skin antisepsis guidelines and an update of the 'rapid sequence spinal'. PMID- 26152256 TI - More than 'fuzzy logic' needed in promoting the use of depth of anaesthesia monitors. PMID- 26152257 TI - Non-surgical site pain - 'movement' toward a solution? PMID- 26152258 TI - Effect of contaminant 0.9% saline on tests of haemostasis. PMID- 26152259 TI - Paediatric anaesthesia neurotoxicity and the 'urgency' of surgery. PMID- 26152260 TI - Suction tube-facilitated videolaryngoscopic intubation. PMID- 26152261 TI - Fractured laryngeal mask. PMID- 26152262 TI - New forceps for videolaryngoscopic intubation. PMID- 26152263 TI - Compliance with the automated machine check. PMID- 26152264 TI - Who is distracting whom? PMID- 26152265 TI - Pre-oxygenation before extubation. PMID- 26152266 TI - A rule of thumb for estimating the lower confidence interval in trials with small event rates. PMID- 26152267 TI - Wrong-site surgical blocks. PMID- 26152268 TI - Correction. PMID- 26152269 TI - The diagnostic value of iron oxide nanoparticles for imaging of myocardial inflammation--quo vadis? AB - Cardiovascular magnetic resonance (CMR) is an integral part in the diagnostic work-up of cardiac inflammatory diseases. In this context, superparamagnetic iron oxide-based contrast agents can provide additional diagnostic information regarding the assessment of myocardial infarction and myocarditis. After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies. Furthermore, first clinical studies with a new iron oxide-complex that was clinically approved for the treatment of iron deficiency anaemia recently demonstrated a superior diagnostic value of iron oxide nanoparticles compared to gadolinium-based compounds for imaging of myocardial inflammation in patients with acute myocardial infarction. In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis. Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy. PMID- 26152270 TI - Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure: An Observational Cohort Study. AB - Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for >=7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3-1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0-3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P<0.001) than at 1, 2, and 5 years after transplant (AUC 0.73, 0.71, and 0.77, respectively, all P<0.001). Independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The discriminatory power of proteinuria for these intragraft injury processes was better in biopsy samples obtained >3 months after transplant (AUC 0.73, P<0.001) than in those obtained earlier (AUC 0.56, P<0.01), with 85% specificity but lower sensitivity (47.8%) for proteinuria >1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis. PMID- 26152271 TI - The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic Lesions. AB - Over 10 years have passed since the latest revision of the histopathologic classification of lupus nephritis. This revision was a significant improvement compared with the previous version, mainly because of clearer and more concise definitions and the elimination of mixed subclasses. Despite these improvements, there are still some difficulties in the classification for lupus nephritis, many of which are in the definitions provided. In this review, we focus on the difficulties surrounding the evaluation of classes III and IV lesions, particularly the definitions of endocapillary and extracapillary proliferation, the use of the terms endocapillary proliferation and hypercellularity, the clinical relevance of segmental and global subdivision in class IV, and the value of distinguishing lesions that indicate activity and chronicity. Vascular and tubulointerstitial lesions are also discussed. Furthermore, we give an overview of the history of the classification to provide background on the origin and development of the definitions in lupus nephritis. The issues raised in this review as well as the suggestions for improvements may assist with a revision of the lupus nephritis classification in the near future. PMID- 26152272 TI - Prevalence of malaria parasites in adults and its determinants in malaria endemic area of Kisumu County, Kenya. AB - BACKGROUND: The prevalence of malaria parasites in adults in Africa is less well researched than in children. Therefore, a demographic surveillance site was used to conduct a household survey of adults in the malaria endemic area of Maseno division in Kisumu County near Lake Victoria. METHODS: A random survey of 1,190 adults living in a demographic health surveillance site in a malaria endemic area of 70,805 population size was conducted, measuring presence of malaria parasites by slide microscopy. Data were analysed using STATA to calculate the prevalence of malaria and associated risk factors. RESULTS: The adult prevalence of presence of malaria parasites in Maseno was 28% (95% CI: 25.4-31.0%). Gender was a significant sociodemographic risk factor in both univariate (OR 1.5, p = 0.005) and multivariate (OR 1.4, p = 0.019) analyses. Females were 50% more likely to have malaria than men. CONCLUSIONS: Presence of malaria parasites is common in the adult population of this endemic area, and the rate is greatly increased in women. The presence of such an adult pool of malaria parasites represents a key reservoir factor in transmission of parasites to children, and is relevant for plans to eradicate malaria. PMID- 26152273 TI - An asymmetric antibody repertoire is shaped between plasmablasts and plasma cells after secondary immunization with (4-hydroxy-3-nitrophenyl)acetyl chicken gamma globulin. AB - Studies on the structural basis of antibody affinity maturation have been carried out by measuring the affinity of secreted antibodies, and information on structures has often been obtained from nucleotide sequences of BCRs of memory B cells. We considered it important to establish whether the repertoire of secreted antibodies from plasma cells is really in accord with that of BCRs on memory B cells at the same time points post-immunization. We isolated plasma cells secreting antibodies specific to (4-hydroxy-3-nitrophenyl)acetyl (NP) hapten by affinity matrix technology using biotin-anti-CD138 and streptavidin-NP allophycocyanin, to which anti-NP antibodies secreted by autologous plasma cells bound preferentially. We found that plasmablasts occupied >90% of the antibody secreting cell compartment in the primary response and that they secreted antibodies whose VH regions were encoded by V186.2(+)Tyr95(+) sequences, which provided an increase in the medium level of affinity by somatic hypermutation (SHM) of heavy chains at position 33. After secondary immunization, a further increase in antibody affinity was observed, which was explained by the appearance of a number of plasma cells secreting V186.2(+)Gly95(+) antibodies that acquired high affinity by multiple SHMs as well as plasmablasts secreting V186.2(+)Tyr95(+) antibodies. However, we did not detect any plasmablasts secreting V186.2(+)Gly95(+) antibodies, showing that plasmablasts and plasma cells have a different antibody repertoire, i.e. their respective repertoires are asymmetric. On the basis of these findings, we discussed the relationship between the BCR affinity of memory B cells and plasmablasts as well as plasma cells as pertaining to their ontogeny. PMID- 26152274 TI - One-Step Nucleic Acid Amplification Assay for Detection of Axillary Lymph Node Metastases in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy. AB - BACKGROUND: The accuracy of one-step nucleic acid amplification (OSNA) for the detection of lymph node (LN) metastasis in breast cancer patients has been well established. This study aimed to evaluate its accuracy for patients treated with neoadjuvant chemotherapy (NAC). METHODS: For this study, 300 LNs, 115 sentinel lymph nodes (SLNs), and 185 non-SLNs from 88 breast cancer patients treated with NAC were examined by means of histology (hematoxylin and eosin staining and pancytokeratin immunostaining) and OSNA. RESULTS: The diagnostic accuracy, sensitivity, and specificity of OSNA were respectively 92.3, 88.5, and 93.3 % for all LNs, and the corresponding values were 87.8, 75.0, and 91.2 % for SLNs and 95.1, 97.3, and 94.6 % for non-SLNs. The diagnostic accuracy of OSNA was significantly lower for SLNs than for non-SLNs (P = 0.021), which was attributable to the low sensitivity for detection of micrometastases (micromets) due to lower CK19 mRNA expression detected by in situ hybridization (ISH) in SLN micromets than in non-SLN micromets. For primary breast tumors, CK19 mRNA expression showed a significant reduction after NAC (P = 0.040). CONCLUSIONS: The diagnostic accuracy of OSNA for NAC-treated patients is similar to that for NAC nontreated patients, but its accuracy is significantly lower for SLNs than for non-SLNs. The findings obtained with CK19 mRNA ISH suggest that most SLN micromets cannot be detected by OSNA due to the reduced expression of CK19 mRNA induced by NAC. PMID- 26152275 TI - The Prognostic Significance of the Early Postoperative Neutrophil-to-Lymphocyte Ratio in Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy. AB - PURPOSE: Because the pretreatment neutrophil-to-lymphocyte ratio (NLR) is a reliable prognostic factor, the authors of this study hypothesized that posttreatment NLR also predicts the survival outcome for cancer patients. The study investigated the clinicopathologic features according to postoperative NLR and determined the prognostic significance of early postoperative NLR for bladder cancer patients undergoing radical cystectomy (RC). METHODS: The study reviewed 385 bladder cancer patients treated with RC and pelvic lymph node dissection at the authors' institution between 1999 and 2012. The primary end points of the study were cancer-specific survival (CSS) and overall survival (OS) estimates from the Kaplan-Meier analysis. Multivariate Cox regression analysis was adopted to identify the independent prognostic factors for oncologic outcomes after surgery. RESULTS: Patients with elevated postoperative NLR (>=2.0) had higher rates of advanced pathologic tumor stage (>=pT3), lymphovascular invasion, and lymph node involvement. Notably, they showed poorer CSS and OS rates than patients with a postoperative NLR lower than 2.0. Additionally, patients with pre and postoperative elevated NLR (>=2.1 -> >=2.0) demonstrated worse oncologic outcomes than other groups of NLR changes. Multivariate analysis showed that early postoperative NLR remained a key predictor for CSS and OS. When divided by pathologic T or N stage, patients with localized pathologic T stage or pN0 status showed significant differences in survival according to early postoperative NLR. CONCLUSION: In summary, postoperative NLR in the early recovery period can be a valuable biomarker for predicting oncologic outcomes for bladder cancer patients undergoing RC. PMID- 26152276 TI - Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Pancreatic Adenocarcinoma: A Decision Analysis. AB - BACKGROUND: Neoadjuvant therapy-based protocols for potentially resectable pancreatic adenocarcinoma (PAC) have not been directly compared with adjuvant protocols in large prospective randomized trials. This study aimed to compare the efficacy of neoadjuvant versus adjuvant therapy-based management by using a formal decision analytic model. METHODS: A decision analytic model was created with a Markov process to compare neoadjuvant and adjuvant chemo- and/or chemoradiation therapy-based strategies for simulated cohorts of patients with potentially resectable PAC. Base-case probabilities were derived from the published data of 21 prospective phases 2 and 3 trials (3708 patients) between 1997 and 2014. The primary outcome measures determined in an intent-to-treat fashion were overall and quality-adjusted survival rates. One- and two-way sensitivity analyses were performed to assess the effects of model uncertainty on outcomes. RESULTS: The median overall survival and 2-year survival rates for the patients in the standard adjuvant therapy arm of the study were 20 months and 42.2 % versus 22 months and 46.8 % for those in the neoadjuvant strategy arm. Quality-adjusted survival was 18.4 and 19.8 months, respectively. Sensitivity analysis demonstrated that when recurrence-free survival after completion of neoadjuvant therapy and resection is less than 13.9 months or when the rate for progression of disease precluding resection during neoadjuvant therapy is greater than 44 %, the neoadjuvant strategy is no longer the favored option. CONCLUSIONS: The decision analytic model suggests that neoadjuvant therapy-based management improves the outcomes for patients with potentially resectable pancreatic cancer. However, the benefits in terms of overall and quality-adjusted survival are modest. PMID- 26152277 TI - Apomixis does not affect visitation to flowers of Melastomataceae, but pollen sterility does. AB - Apomixis is an asexual seed reproduction mechanism thorough which embryos are originated from material tissues inside the ovules, without precedent fertilisation. It allows plants to colonise new habitats, even in places where flower visitors are scarce or where plants are isolate. Apomixis seems to be related to pollen sterility and, in species with flowers that offer pollen as a reward for pollinators, the amount or quality of the pollen offered by these species may influence the amount of the visits and specific composition of the visitors. In order to test this hypothesis, we studied breeding systems of 16 species of Melastomataceae and their flower visitors, evaluating composition and abundance of the visits to apomictic and sexual species. Apomictic plants with no viable pollen or with pollen with low viability did not receive visits from pollinators, and consequently probably produce strictly apomictic fruits. On the other hand, apomictic and sexual plants with high pollen viability do receive visits; in this case, apomictic plants may produce fruits and seeds through both sexual and apomictic methods. The species composition of insects visiting Melastomataceae with high pollen viability was similar, regardless of whether the plants were apomictic or not. It seems that pollen viability levels are important to determine visits to the flowers irrespective of breeding system. PMID- 26152278 TI - Potential effect of cationic liposomes on interactions with oral bacterial cells and biofilms. AB - CONTEXT: Although oral infectious diseases have been attributed to bacteria, drug treatments remain ineffective because bacteria and their products exist as biofilms. Cationic liposomes have been suggested to electrostatically interact with the negative charge on the bacterial surface, thereby improving the effects of conventional drug therapies. However, the electrostatic interaction between oral bacteria and cationic liposomes has not yet been examined in detail. OBJECTIVE: The aim of the present study was to examine the behavior of cationic liposomes and Streptococcus mutans in planktonic cells and biofilms. MATERIALS AND METHODS: Liposomes with or without cationic lipid were prepared using a reverse-phase evaporation method. The zeta potentials of conventional liposomes (without cationic lipid) and cationic liposomes were -13 and 8 mV, respectively, and both had a mean particle size of approximately 180 nm. We first assessed the interaction between liposomes and planktonic bacterial cells with a flow cytometer. We then used a surface plasmon resonance method to examine the binding of liposomes to biofilms. We confirmed the binding behavior of liposomes with biofilms using confocal laser scanning microscopy. RESULTS: The interactions between cationic liposomes and S. mutans cells and biofilms were stronger than those of conventional liposomes. Microscopic observations revealed that many cationic liposomes interacted with the bacterial mass and penetrated the deep layers of biofilms. DISCUSSION AND CONCLUSION: In this study, we demonstrated that cationic liposomes had higher affinity not only to oral bacterial cells, but also biofilms than conventional liposomes. This electrostatic interaction may be useful as a potential drug delivery system to biofilms. PMID- 26152279 TI - Controlled release of injectable liposomal in situ gel loaded with recombinant human bone morphogenetic protein-2 for the repair of alveolar bone clefts in rabbits. AB - BACKGROUND AND OBJECTIVE: The aim of the present study was to develop and examine a new non-invasive injectable graft for the repair of alveolar bone clefts using recombinant human bone morphogenetic protein-2 (rhBMP-2) encapsulated within injectable liposomal in situ gel (LIG). METHOD: Different liposomal formulations loaded with rhBMP-2 were prepared, and the effects of the preparation methods and lipid content on the efficiency of rhBMP-2 encapsulation within the liposomes were studied. For the preparation of in situ gel, deacetylated gellan gum (DGG) was used, and the in vitro gelation characteristics of the gel were evaluated. In vivo pharmacokinetics and histology were also assessed. Critical size alveolar defects were surgically created in the maxillae of 30 New Zealand rabbits and treated with different injectable formulae, including rhBMP-2 liposomes and in situ gel (rhBMP-2-LIG). RESULTS: The results indicated that the prepared rhBMP-2 LIG prolonged the release and residence time of BMP-2 within rabbits for more than 7 days. Histomorphometric assessment showed 67% trabecular bone filling of the defects treated using this novel formula. CONCLUSION: BMP-2-LIG is a promising delivery device for the repair of alveolar bone defects associated with cleft deformities. PMID- 26152280 TI - Authors' reply to Males. PMID- 26152281 TI - IGF-1 decreases portal vein endotoxin via regulating intestinal tight junctions and plays a role in attenuating portal hypertension of cirrhotic rats. AB - BACKGROUND: Intestinal barrier dysfunction is not only the consequence of liver cirrhosis, but also an active participant in the development of liver cirrhosis. Previous studies showed that external administration of insulin-like growth factor 1 (IGF-1) improved intestinal barrier function in liver cirrhosis. However, the mechanism of IGF-1 on intestinal barrier in liver cirrhosis is not fully elucidated. The present study aims to investigate the mechanisms of IGF-1 improving intestinal barrier function via regulating tight junctions in intestines. METHODS: We used carbon tetrachloride induced liver cirrhotic rats to investigate the effect of IGF-1 on intestinal claudin-1 and occludin expressions, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, severity of liver fibrosis, portal pressures, enterocytic apoptosis and lipopolysaccharides (LPS) levels in portal vein. The changes of IGF-1 in serum during the development of rat liver cirrhosis were also evaluated. Additionally, we assessed the effect of IGF-1 on claudin-1 and occludin expressions, changes of transepithelial electrical resistance (TEER) and apoptosis in Caco-2 cells to confirm in vivo findings. RESULTS: Serum IGF-1 levels were decreased in the development of rat liver cirrhosis, and external administration of IGF-1 restored serum IGF-1 levels. External administration of IGF-1 reduced serum ALT and AST levels, severity of liver fibrosis, LPS levels in portal vein, enterocytic apoptosis and portal pressure in cirrhotic rats. External administration of IGF-1 increased the expressions of claudin-1 and occludin in enterocytes, and attenuated tight junction dysfunction in intestines of cirrhotic rats. LPS decreased TEER in Caco-2 cell monolayer. LPS also decreased claudin-1 and occludin expressions and increased apoptosis in Caco-2 cells. Furthermore, IGF-1 attenuated the effect of LPS on TEER, claudin-1 expression, occludin expression and apoptosis in Caco-2 cells. CONCLUSIONS: Tight junction dysfunction develops during the development of liver cirrhosis, and endotoxemia will develop subsequently. Correspondingly, increased endotoxin in portal system worsens tight junction dysfunction via decreasing intestinal occludin and claudin-1 expressions and increasing enterocytic apoptosis. Endotoxemia and intestinal barrier dysfunction form a vicious circle. External administration of IGF-1 breaks this vicious circle. Improvement of tight junctions might be one possible mechanism of the restoration of intestinal barrier function mediated by IGF-1. PMID- 26152282 TI - A fluorescence-based bioassay for antibacterials and its application in screening natural product extracts. AB - The reliable assessment of the biological activity of a minor component embedded in a complex matrix of several hundred compounds is a difficult but common task in the search for natural product-based antibiotics, for example, by bioassay guided fractionation. To quantify the antibiotic properties, it is necessary to assess the cell viability. Direct measurements use CFU counts, OD measurements or detection via fluorescent or reducible dyes. However, natural extracts often already possess intrinsic dye, fluorescent, reducing or protein denaturing properties, or they contain insoluble compounds or general protein-binding (tanning) polyphenols as disturbing features, while at the same time very little of the selective antibiotic sought after is present. A promising alternative is provided by intrinsically produced bright fluorescent proteins. In this paper, a rapid, robust and concentration-dependent assay for screening antibiotics with genetically modified mutants of Bacillus subtilis 168 (PabrB-iyfp) is presented. The Gram-positive bacteria exhibit a native fluorescence during their exponential growth phase due to the expression of improved yellow fluorescent protein. To demonstrate the applicability in the field of natural product research, several compounds and extracts were screened for antibacterial activity, with an emphasis on those from the fungal genus Hygrophorus (waxy caps). PMID- 26152283 TI - MBJ-0110, a novel cyclopeptide isolated from the fungus Penicillium sp. f25267. PMID- 26152284 TI - Viral expression of ALS-linked ubiquilin-2 mutants causes inclusion pathology and behavioral deficits in mice. AB - BACKGROUND: UBQLN2 mutations have recently been associated with familial forms of amyotrophic lateral sclerosis (ALS) and ALS-dementia. UBQLN2 encodes for ubiquilin-2, a member of the ubiquitin-like protein family which facilitates delivery of ubiquitinated proteins to the proteasome for degradation. To study the potential role of ubiquilin-2 in ALS, we used recombinant adeno-associated viral (rAAV) vectors to express UBQLN2 and three of the identified ALS-linked mutants (P497H, P497S, and P506T) in primary neuroglial cultures and in developing neonatal mouse brains. RESULTS: In primary cultures rAAV2/8-mediated expression of UBQLN2 mutants resulted in inclusion bodies and insoluble aggregates. Intracerebroventricular injection of FVB mice at post-natal day 0 with rAAV2/8 expressing wild type or mutant UBQLN2 resulted in widespread, sustained expression of ubiquilin-2 in brain. In contrast to wild type, mutant UBQLN2 expression induced significant pathology with large neuronal, cytoplasmic inclusions and ubiquilin-2-positive aggregates in surrounding neuropil. Ubiquilin 2 inclusions co-localized with ubiquitin, p62/SQSTM, optineurin, and occasionally TDP-43, but were negative for alpha-synuclein, neurofilament, tau, and FUS. Mutant UBLQN2 expression also resulted in Thioflavin-S-positive inclusions/aggregates. Mice expressing mutant forms of UBQLN2 variably developed a motor phenotype at 3-4 months, including nonspecific clasping and rotarod deficits. CONCLUSIONS: These findings demonstrate that UBQLN2 mutants (P497H, P497S, and P506T) induce proteinopathy and cause behavioral deficits, supporting a "toxic" gain-of-function, which may contribute to ALS pathology. These data establish also that our rAAV model can be used to rapidly assess the pathological consequences of various UBQLN2 mutations and provides an agile system to further interrogate the molecular mechanisms of ubiquilins in neurodegeneration. PMID- 26152285 TI - Interaction between microRNA-181a and TNFAIP1 regulates pancreatic cancer proliferation and migration. AB - We investigated the role of microRNA 181a (miR-181a) and its downstream target tumor necrosis factor, alpha-induced protein 1 (TNFAIP1) in pancreatic cancer regulation. Quantitative real-time PCR (qRT-PCR) was applied to evaluate the gene expression of miR-181a in seven pancreatic cancer cell lines. MiR-181a inhibitor lentivirus (miR-181a-IN) was used to down-regulate miR-181a in Capan-1 and AsPC-1 cells. The effects of miR-181a down-regulation on pancreatic cancer were evaluated by in vitro proliferation assay and migration assay. Targeting of miR 181a on TNFAIP1 in pancreatic cancer was evaluated by dual-luciferase reporter assay and western blot. TNFAIP1 was either upregulated by pcDNA3.1 (+) expression vector or down-regulated by siRNA in Capan-1 and AsPC-1 cells. The subsequent effects of TNFAIP1 upregulation or down-regulation on miR-181a mediated pancreatic cancer regulation were also evaluated through in vitro proliferation and migration assays. The in vivo effect of miR-181a down-regulation on pancreatic tumor growth was evaluated by a xenograft assay. MiR-181a was consistently upregulated in pancreatic cancer cell lines. MiR-181a down regulation inhibited proliferation and migration in vitro, and upregulated TNFAIP1 in pancreatic cancer cells. Ectopic TNFAIP1 overexpression had similar tumor-suppressive effects on pancreatic cancer proliferation and migration as miR 181a down-regulation, whereas siRNA-mediated TNFAIP1 down-regulation had opposite or oncogenic effects on pancreatic cancer. In vivo pancreatic xenograft showed miR-181a recapitulated the in vitro anti-tumor effects and its regulation on TNFAIP1. MiR-181a played a critical role in regulating pancreatic cancer growth and migration, likely interacting with TNFAIP1. PMID- 26152286 TI - MicroRNA 211 expression is upregulated and associated with poor prognosis in colorectal cancer: a case-control study. AB - Increasingly more evidence support the role of the microRNAs (miRNA) in tumorigenesis. The role of up/downregulation microRNA-211 (miR-211) during human tumorigenesis is still contentious and may exhibit tissue-specific regulatory manner, but the exhaustive mechanisms underlying its pro/anti-oncogenic effects remain to be unknown. Sixty-six patients that were diagnosed and operated with colorectal cancer (CRC) and sixty-five healthy cases that were age and sex compatible with them were included in our study. miRNA was isolated from the formalin-fixed paraffin-embedded (FFPE) tissues of all cases. The expression level of miR-211 in matched normal and tumor tissues of CRC group and healthy group was evaluated using a quantitative real-time RT-PCR (qRT-PCR). Based on the average miR-211 levels, two groups of low or high expression were formed in CRC group. Correlation of the patients' clinicopathological factors and survival was also analyzed. No statistically significant differences were found in miR-211 levels among tumorous and normal tissues of CRC patient group (P = 0.59). Also, no statistically significant correlation was determined between clinicopathological factors and miR-211 expression level in CRC group. However, miR-211 expression levels between the CRC group and the healthy group were determined to be of statistical significance (P < 0.0001). There were 33 (50 %) CRC patients that expressed low levels of miR-211 and 33 (50 %) CRC patients that expressed high levels of miR-211. A median survival between low levels of miR-211 group and high levels of miR-211 group was evaluated via Kaplan-Meier, and the difference was of statistical significance (P = 0.035). The univariate analysis of the factors that may affect survival indicated invasion depth (P = 0.063), lymphovascular invasion (P = 0.011), perineural invasion (P = 0.009), and miR-211 expression level (P = 0.041) presence to be effective. In the multivariate analysis of these factors with overall survival, only miR-211 expression level (P = 0.01) was effective on overall survival. Our results suggest for the first time that miR-211 expressed more in CRC patients than in healthy group could be a new prognostic biomarker in order to predict survival. Independent studies are needed to validate our findings in a larger series, as well as in cancer of different tissues. PMID- 26152287 TI - High expression of OCT4 is frequent and may cause undesirable treatment outcomes in patients with acute myeloid leukemia. AB - In recent years, many researches have shown that OCT4 is overexpressed in both germ cell tumors and somatic cancers. Meanwhile, OCT4 has relationship with poor prognosis in a lot of solid tumors, such as hepatocellular carcinoma, gastric cancer, and esophageal cancer. In our study, we investigated the expression status of OCT4 and its clinical significance in patients with acute myeloid leukemia (AML) using real-time quantitative PCR. The receiver operating characteristic (ROC) curve reveals that the level of OCT4 expression could be available for a potential diagnostic biomarker for differentiating AML from controls with an area under the ROC curve (AUC) of 0.915 (95 % confidence interval (CI) 0.837-0.992; P < 0.001). At the cutoff value of 0.56, the sensitivity and the specificity are 75.9 and 81.2 %, respectively. The amount of white blood cell (WBC) of patients with high OCT4 expression is higher than that of patients with low OCT4 expression (18.2 * 10(9) versus 2.7 * 10(9) L(-1), P = 0.001). Among those patients who are less than 70 years old, patients with OCT4 high expression have significantly shorter overall survival (OS) than those without OCT4 high expression (P = 0.048). These findings suggest that OCT4 high expression is a common event and may have an adverse impact on prognosis in AML. PMID- 26152288 TI - Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast. AB - Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context. PMID- 26152289 TI - Association between cell cycle gene transcription and tumor size in oral squamous cell carcinoma. AB - Higher tumor size correlates with poor prognosis and is an independent predictive survival factor in oral squamous cell carcinoma (OSCC) patients. However, the molecular events underlining OSCC tumor evolution are poorly understood. We aimed to investigate if large OSCC tumors show different cell cycle gene transcriptional signature compared to small tumors. Seventeen fresh OSCC tumor samples with different tumor sizes (T) were included in the study. Tumors were from the tongue or from the floor of the mouth, and only three patients were nonsmokers. Samples were categorized according to clinical tumor size in tumors <=2 cm (T1, n = 5) or tumors >2 cm (T2, n = 9; T3, n = 2; T4, n = 1). The group of tumors <=2 cm was considered the reference group, while the larger tumors were considered the test group. We assessed the expression of 84 cell cycle genes by qRT-PCR array and normalized it to the expression of two housekeeping genes. Results were analyzed according to the formula 2(^-DeltaCt). A five-fold change cutoff was used, and p values <0.05 were considered statistically significant. Ki 67 immunohistochemistry was performed to estimate cell proliferation index. Twenty-nine genes were downregulated in the test group (larger tumors) compared to the reference group (smaller tumors). Among these genes, 13 reached statistical significance: ANAPC4, CUL1, SUMO1, KPNA2, MAD2L2, CCNG2, E2F4, NBN, CUL2, PCNA, TFDP1, KNTC1, and ATR. Ki-67 labeling index was similar in both tumor groups. Our findings suggest that the transcriptional activity of specific cell cycle genes varies according to the size of OSCC tumor, which probably reflects tumor molecular evolution and adaptation to the microenvironment. PMID- 26152291 TI - Is Co-norming Required? AB - Researchers who have been responsible for developing test batteries have argued that competent practice requires the use of a "fixed battery" that is co-normed. We tested this assumption with three normative systems: co-normed, meta-regressed norms and a system of these two methods. We analyzed two samples: 330 referred patients and 99 undergraduate volunteers. The T scores generated for referred patients using the three systems were highly associated with one another and quite similar in magnitude, with an Overall Test Battery Means (OTBMs) using the co-normed, hybrid, and meta-regressed scores equaled 43.8, 45.0, and 43.9, respectively. For volunteers, the OTBMs equaled 47.4, 47.5, and 47.1, respectively. The correlations amongst these OTBMs across systems were all above .90. Differences among OTBMs across normative systems were small and not clinically meaningful. We conclude that co-norming for competent clinical practice is not necessary. PMID- 26152290 TI - Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy. AB - In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation. PMID- 26152292 TI - The immunomodulatory function of mesenchymal stem cells: mode of action and pathways. AB - Mesenchymal stem cells (MSCs) are being increasingly investigated as a therapeutic alternative, not only for their possible regenerative potential but also for their immunomodulatory action, which is being exploited for controlling diseases associated with inflammation. Understanding their direct and indirect target cells, as well as their mode of action and relevant pathways, is a prerequisite for the appropriate and optimal use of MSCs in therapy. Here, we review recent findings on the effects of MSCs on adaptive and innate immune cells. We also consider the impact of the environment on MSC profile, both anti- and proinflammatory, and the mechanisms and molecular pathways through which their effects are mediated, both at the MSC and target cell levels. PMID- 26152293 TI - Letter by Liu et al Regarding Article, "Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke". PMID- 26152294 TI - Twenty-Year History of the Evolution of Stroke Thrombolysis With Intravenous Alteplase to Reduce Long-Term Disability. PMID- 26152295 TI - Response to Letter Regarding Article, "Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke". PMID- 26152296 TI - Duration of Diabetes Mellitus and Risk of Thromboembolism and Bleeding in Atrial Fibrillation: Nationwide Cohort Study. AB - BACKGROUND AND PURPOSE: Guidelines advocate anticoagulant treatment to all patients with atrial fibrillation and concomitant diabetes mellitus. The potential refinement to thromboembolic risk stratification that may spring from subdividing diabetes mellitus is unexplored. The purpose was to investigate duration of diabetes mellitus as a predictor of thromboembolism and anticoagulant related bleeding in patients with atrial fibrillation. METHODS: Using nationwide Danish registries, we identified all patients discharged from hospital with an incident diagnosis of atrial fibrillation from 2000 to 2011. Hazard ratios with 95% confidence intervals for thromboembolism and bleeding according to years of diabetes mellitus duration in categories (0-4, 5-9, 10-14, and >=15) and as a continuous variable using cubic splines were calculated by Cox regression. RESULTS: The study population comprised 137 222 patients with atrial fibrillation, of which 12.4% had diabetes mellitus. Compared with patients without diabetes mellitus and after adjustment for anticoagulant treatment and CHA2DS2-VASc components (congestive heart failure, hypertension, age, previous stroke, vascular disease, and sex), the risk of thromboembolism was lowest in the 0 to 4 years duration category (hazard ratio, 1.11; 95% confidence interval, 1.03 1.20), and highest in the longest duration category of >=15 years (hazard ratio, 1.48; 95% confidence interval, 1.29-1.70). When analyzed as a continuous variable, duration of diabetes mellitus was associated with risk of thromboembolism in a dose-response-dependent manner, but not with a higher risk of bleeding during anticoagulant treatment. CONCLUSIONS: In patients with atrial fibrillation, longer duration of diabetes mellitus was associated with a higher risk of thromboembolism, but not with a higher risk of anticoagulant-related bleeding. Considering the critical balance between preventing thromboembolism and avoiding bleeding, longer duration of diabetes mellitus may favor initiation of anticoagulant therapy. PMID- 26152297 TI - Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times. AB - BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain. METHODS: The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level. RESULTS: Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment. CONCLUSIONS: Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke. PMID- 26152299 TI - Are We Barking Up the Wrong Vessels? Cerebral Microcirculation After Subarachnoid Hemorrhage. PMID- 26152298 TI - Cluster Randomized Controlled Trial: Clinical and Cost-Effectiveness of a System of Longer-Term Stroke Care. AB - BACKGROUND AND PURPOSE: We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. METHODS: A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self completed postal questionnaires at 6 and 12 months. RESULTS: Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was -0.6 points (95% confidence interval, -1.8 to 0.7; P=0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. CONCLUSIONS: This robust trial demonstrated no benefit in clinical or cost effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN 67932305. PMID- 26152300 TI - Intraductal papillary mucinous carcinoma of the pancreas associated with pancreas divisum: a case report and review of the literature. AB - BACKGROUND: Pancreas divisum, the most common congenital anomaly of the pancreas, is caused by failure of the fusion of the ventral and dorsal pancreatic duct systems during embryological development. Although various pancreatic tumors can occur in patients with pancreas divisum, intraductal papillary mucinous neoplasm is rare. CASE PRESENTATION: A 77-year-old woman was referred to our hospital because she was incidentally found to have a cystic tumor in her pancreas at a regular health checkup. Contrast-enhanced abdominal computed tomography images demonstrated a cystic tumor in the head of the pancreas measuring 40 mm in diameter with slightly enhancing mural nodules within the cyst. Endoscopic retrograde pancreatography via the major duodenal papilla revealed a cystic tumor and a slightly dilated main pancreatic duct with an abrupt interruption at the head of the pancreas. The orifice of the major duodenal papilla was remarkably dilated and filled with an abundant extrusion of mucin, and the diagnosis based on pancreatic juice cytology was "highly suspicious for adenocarcinoma". Magnetic resonance cholangiopancreatography depicted a normal, non-dilated dorsal pancreatic duct throughout the pancreas. The patient underwent a pylorus preserving pancreaticoduodenectomy under the diagnosis of intraductal papillary mucinous neoplasm with suspicion of malignancy arising in the ventral part of the pancreas divisum. A pancreatography via the major and minor duodenal papillae on the surgical specimen revealed that the ventral and dorsal pancreatic ducts were not connected, and the tumor originated in the ventral duct, i.e., the Wirsung's duct. Microscopically, the tumor was diagnosed as intraductal papillary mucinous carcinoma with microinvasion. In addition, marked fibrosis with acinar cell depletion was evident in the ventral pancreas, whereas no fibrotic change was noted in the dorsal pancreas. CONCLUSION: Invasive ductal carcinomas of the pancreas associated with pancreas divisum usually arise from the dorsal pancreas, in which the occurrence of pancreatic cancer may link to underlying longstanding chronic pancreatitis in the dorsal pancreas; however, the histopathogenesis of intraductal papillary mucinous neoplasm in this anomaly is a critical issue that warrants further investigation in future. PMID- 26152301 TI - Different motif requirements for the localization zipcode element of beta-actin mRNA binding by HuD and ZBP1. AB - Interactions of RNA-binding proteins (RBPs) with their target transcripts are essential for regulating gene expression at the posttranscriptional level including mRNA export/localization, stability, and translation. ZBP1 and HuD are RBPs that play pivotal roles in mRNA transport and local translational control in neuronal processes. While HuD possesses three RNA recognition motifs (RRMs), ZBP1 contains two RRMs and four K homology (KH) domains that either increase target specificity or provide a multi-target binding capability. Here we used isolated cis-element sequences of the target mRNA to examine directly protein-RNA interactions in cell-free systems. We found that both ZBP1 and HuD bind the zipcode element in rat beta-actin mRNA's 3' UTR. Differences between HuD and ZBP1 were observed in their binding preference to the element. HuD showed a binding preference for U-rich sequence. In contrast, ZBP1 binding to the zipcode RNA depended more on the structural level, as it required the proper spatial organization of a stem-loop that is mainly determined by the U-rich element juxtaposed to the 3' end of a 5'-ACACCC-3' motif. On the basis of this work, we propose that ZBP1 and HuD bind to overlapping sites in the beta-actin zipcode, but they recognize different features of this target sequence. PMID- 26152302 TI - SUV3 helicase is required for correct processing of mitochondrial transcripts. AB - Mitochondrial gene expression is largely regulated by post-transcriptional mechanisms that control the amount and translation of each mitochondrial mRNA. Despite its importance for mitochondrial function, the mechanisms and proteins involved in mRNA turnover are still not fully characterized. Studies in yeast and human cell lines have indicated that the mitochondrial helicase SUV3, together with the polynucleotide phosphorylase, PNPase, composes the mitochondrial degradosome. To further investigate the in vivo function of SUV3 we disrupted the homolog of SUV3 in Drosophila melanogaster (Dm). Loss of dmsuv3 led to the accumulation of mitochondrial mRNAs, without increasing rRNA levels, de novo transcription or decay intermediates. Furthermore, we observed a severe decrease in mitochondrial tRNAs accompanied by an accumulation of unprocessed precursor transcripts. These processing defects lead to reduced mitochondrial translation and a severe respiratory chain complex deficiency, resulting in a pupal lethal phenotype. In summary, our results propose that SUV3 is predominantly required for the processing of mitochondrial polycistronic transcripts in metazoan and that this function is independent of PNPase. PMID- 26152303 TI - Synthetic biosensors for precise gene control and real-time monitoring of metabolites. AB - Characterization and standardization of inducible transcriptional regulators has transformed how scientists approach biology by allowing precise and tunable control of gene expression. Despite their utility, only a handful of well characterized regulators exist, limiting the complexity of engineered biological systems. We apply a characterization pipeline to four genetically encoded sensors that respond to acrylate, glucarate, erythromycin and naringenin. We evaluate how the concentration of the inducing chemical relates to protein expression, how the extent of induction affects protein expression kinetics, and how the activation behavior of single cells relates to ensemble measurements. We show that activation of each sensor is orthogonal to the other sensors, and to other common inducible systems. We demonstrate independent control of three fluorescent proteins in a single cell, chemically defining eight unique transcriptional states. To demonstrate biosensor utility in metabolic engineering, we apply the glucarate biosensor to monitor product formation in a heterologous glucarate biosynthesis pathway and identify superior enzyme variants. Doubling the number of well-characterized inducible systems makes more complex synthetic biological circuits accessible. Characterizing sensors that transduce the intracellular concentration of valuable metabolites into fluorescent readouts enables high throughput screening of biological catalysts and alleviates the primary bottleneck of the metabolic engineering design-build-test cycle. PMID- 26152304 TI - A new method to prevent carry-over contaminations in two-step PCR NGS library preparations. AB - Two-step PCR procedures are an efficient and well established way to generate amplicon libraries for NGS sequencing. However, there is a high risk of cross contamination by carry-over of amplicons from first to second amplification rounds, potentially leading to severe misinterpretation of results. Here we describe a new method able to prevent and/or to identify carry-over contaminations by introducing the K-box, a series of three synergistically acting short sequence elements. Our K-boxes are composed of (i) K1 sequences for suppression of contaminations, (ii) K2 sequences for detection of possible residual contaminations and (iii) S sequences acting as separators to avoid amplification bias. In order to demonstrate the effectiveness of our method we analyzed two-step PCR NGS libraries derived from a multiplex PCR system for detection of T-cell receptor beta gene rearrangements. We used this system since it is of high clinical relevance and may be affected by very low amounts of contaminations. Spike-in contaminations are effectively blocked by the K-box even at high rates as demonstrated by ultra-deep sequencing of the amplicons. Thus, we recommend implementation of the K-box in two-step PCR-based NGS systems for research and diagnostic applications demanding high sensitivity and accuracy. PMID- 26152306 TI - Study overestimates depression due to victimisation in adolescence. PMID- 26152305 TI - Upregulating endogenous genes by an RNA-programmable artificial transactivator. AB - To promote expression of endogenous genes ad libitum, we developed a novel, programmable transcription factor prototype. Kept together via an MS2 coat protein/RNA interface, it includes a fixed, polypeptidic transactivating domain and a variable RNA domain that recognizes the desired gene. Thanks to this device, we specifically upregulated five genes, in cell lines and primary cultures of murine pallial precursors. Gene upregulation was small, however sufficient to robustly inhibit neuronal differentiation. The transactivator interacted with target gene chromatin via its RNA cofactor. Its activity was restricted to cells in which the target gene is normally transcribed. Our device might be useful for specific applications. However for this purpose, it will require an improvement of its transactivation power as well as a better characterization of its target specificity and mechanism of action. PMID- 26152307 TI - Identification of miRNAs during mouse postnatal ovarian development and superovulation. AB - BACKGROUND: MicroRNAs are small noncoding RNAs that play critical roles in regulation of gene expression in wide array of tissues including the ovary through sequence complementarity at post-transcriptional level. Tight regulation of multitude of genes involved in ovarian development and folliculogenesis could be regulated at transcription level by these miRNAs. Therefore, tissue specific miRNAs identification is considered a key step towards understanding the role of miRNAs in biological processes. METHODS: To investigate the role of microRNAs during ovarian development and folliculogenesis we sequenced eight different libraries using Illumina deep sequencing technology. Different developmental stages were selected to explore miRNAs expression pattern at different stages of gonadal maturation with/without treatment of PMSG/hCG for superovulation. RESULTS: From massive sequencing reads, clean reads of 16-26 bp were selected for further analysis of differential expression analysis and novel microRNA annotation. Expression analysis of all miRNAs at different developmental stages showed that some miRNAs were present ubiquitously while others were differentially expressed at different stages. Among differentially expressed miRNAs we reported 61 miRNAs with a fold change of more than 2 at different developmental stages among all libraries. Among the up-regulated miRNAs, mmu-mir 1298 had the highest fold change with 4.025 while mmu-mir-150 was down-regulated more than 3 fold. Furthermore, we found 2659 target genes for 20 differentially expressed microRNAs using seven different target predictions programs (DIANA-mT, miRanda, miRDB, miRWalk, RNAhybrid, PICTAR5, TargetScan). Analysis of the predicted targets showed certain ovary specific genes targeted by single or multiple microRNAs. Furthermore, pathway annotation and Gene ontology showed involvement of these microRNAs in basic cellular process. CONCLUSIONS: These results suggest the presence of different miRNAs at different stages of ovarian development and superovulation. Potential role of these microRNAs was elucidated using bioinformatics tools in regulation of different pathways, biological functions and cellular components underlying ovarian development and superovulation. These results provide a framework for extended analysis of miRNAs and their roles during ovarian development and superovulation. Furthermore, this study provides a base for characterization of individual miRNAs to discover their role in ovarian development and female fertility. PMID- 26152309 TI - Even small brain lesions raise risk of stroke and death, study finds. PMID- 26152308 TI - Senior orienteering athletes as a model of healthy aging: a mixed-method approach. AB - BACKGROUND: The proportion of individuals reaching an old age is increasing and will, in the near future consume a majority of health care resources. It is therefore essential to facilitate the maintenance of optimal functionality among older adults. By characterizing older individuals experiencing wellbeing, factors important to promote and maintain health through life can be identified. Orienteering is an endurance-running sport involving cross-country navigation, demanding both cognitive and physical skills of its practitioners. In this study we aim to explore a Swedish population of senior orienteering athletes as a potential model of healthy aging. METHODS: We undertook a mixed-method approach using quantitative (i.e. questionnaires) and qualitative (i.e. focus group discussions) methodologies to explore a population of senior orienteering athletes (n = 136, median age = 69 (67-71) years). Quantitative data was collected to evaluate health status, assessing physical activity (Frandin-Grimby activity scale (FGAS)), functional wellbeing (EQ-5D-5 L), gut health (Gastrointestinal symptoms rating scale (GSRS)), anxiety and depression (Hospital Anxiety and Depression scale (HADS)) and overall health (Health index (HI)). The data was further compared to reference values obtained from a free-living Swedish population of older adults. Focus group discussions (FGD) were performed as a complement to the quantitative data to facilitate the individuals' own views on health and physical activity. RESULTS: The orienteering athletes enrolled in the study reported a significantly better health compared to the free-living older adults (p <0.0015) on all questionnaires except HADS. The high health status displayed in this population was further confirmed by the FGD findings, in which all participants declared their engagement in orienteering as a prerequisite for health. CONCLUSIONS: In conclusion our results show that senior orienteering may represent an ideal model in studies of healthy aging. Furthermore, our results show that even though the senior orienteering athletes are well aware of the long term benefits of physical activity and have practiced the sport from a young age, they particularly point out that their engagement in orienteering is driven by short-term values such as enjoyment and passion. This may be important to consider when introducing public health interventions among the general older population. PMID- 26152310 TI - Oxidative stress markers in saliva and periodontal disease status: modulation during pregnancy and postpartum. AB - BACKGROUND: Periodontal diseases may affect local and systemic inflammation, and reactive oxygen species (ROS) levels. This systemic health burden could compromise the outcome of pregnancy in expectant mothers. The aim of the present study was to evaluate oxidative stress markers, including glutathione peroxidase (GPx), thiobarbituric acid-reactive substances (TBARS) and 8-hydroxy-2' deoxyguanosine (8-OHdG), and total bacterial loads in the saliva of pregnant and postpartum women, and to investigate their association with periodontal disease severity. METHODS: A total of 187 women were originally recruited for this case control study, assigned to the following groups a) pregnant group, b) postpartum group: the pregnant group re-evaluated 6 months after giving birth, c) control group: systemically healthy and non-pregnant women. The levels of the studied oxidative stress markers in saliva were measured by commercially available kits. RESULTS: The levels of salivary 8-OHdG were significantly elevated in the pregnant, compared with the control group. Although salivary 8-OHdG levels slightly decreased after giving birth (postpartum group), the difference did not reach significance. In contrast, the activity of antioxidant enzyme GPx in saliva was significantly lower in the pregnant than the control group. Although no differences in lipid peroxidation (represented by TBARS) were observed between the pregnant and control groups, after giving birth TBARS levels were significantly lowered. Only in the postpartum and control groups did clinical measurements of periodontal disease severity correlate with oxidative stress markers. Interestingly, there were no such correlations with TBARS in the pregnant and postpartum groups. CONCLUSIONS: The present study shows changes in the oxidant/antioxidant balance in saliva during pregnancy and after birth, which may be affected by periodontal health status in the latter case. Whether this is associated with adverse pregnancy outcomes, or not, remains to be elucidated. Early identification of ROS markers in saliva may be of clinical value in the periodontal management of pregnant women. PMID- 26152312 TI - Problems with the diagnostic algorithm for hypercalcaemia. PMID- 26152311 TI - Case report of a patient with progressive multifocal leukoencephalopathy under treatment with dimethyl fumarate. AB - BACKGROUND: Progressive multifocal leukoencephalopathy is a severe demyelinating disease caused by the polyoma JC virus in patients with reduced immunocompetence. A few cases of progressive multifocal leukoencephalopathy have been reported in patients treated with fumaric acid esters. CASE PRESENTATION: A 53-year-old Caucasian woman reported to our clinic with a first focal epileptic seizure and mild cognitive impairment. Since 1.5 years, she was treated with fumaderm for her psoriasis. During that time, her lymphocyte counts ranged between 450 and 700/MUl. Cerebral magnet resonance imaging showed multifocal subcortical T2 hyperintense lesions with partial gadolinium enhancement. She did not have antibodies against human immunodeficiency virus 1 and 2 and cerebrospinal fluid polymerase chain reaction for viral infections including a sensitive JC-virus polymerase chain reaction were negative. The diagnosis of progressive multifocal leukoencephalopathy was established by histological analysis and detection of JC virus desoxyribonucleic acid in brain biopsy specimens. Dimethyl fumarate was stopped and Mirtazapin and Mefloquin were initiated. Neurological examination and imaging remained stable. CONCLUSIONS: Progressive multifocal leukoencephalopathy can occur in patients with lymphocyte counts between 450 and 700/MUl, produce only faint symptoms and is not excluded by negative JC-virus-polymerase chain reaction in cerebrospinal fluid. The incidence of progressive multifocal leukoencephalopathy may thus be underestimated and a more careful surveillance of patients would be necessary. PMID- 26152313 TI - Differences in alarm calls of juvenile and adult European ground squirrels (Spermophilus citellus): Findings on permanently marked animals from a semi natural enclosure. AB - The European ground squirrel (Spermophilus citellus) emits alarm calls that warn conspecifics of potential danger. Although it has been observed that inexperienced juveniles of this species emit alarm calls that sound similar to those of adults, studies focusing on juvenile alarm calls are lacking. We analyzed the acoustic structure of alarm calls emitted by six permanently marked European ground squirrels living in a semi-natural enclosure when they were juveniles and after 1 year as adults. We found that the acoustic structure of the juvenile alarm calls was significantly different from those of adults and that the alarm calls underwent nearly the same changes in all studied individuals. All juveniles emitted alarm calls consisting of one element with almost constant frequency, but their alarm calls included a second frequency-modulated element after their first hibernation as adults. Our data show that the duration of the first element is significantly shorter in adults than in juveniles. Additionally, the frequency of the first element is significantly higher in adults than in juveniles. Similar to previous findings in other Palearctic ground squirrel species, our data are inconsistent with the assumption that juvenile mammals emit vocalizations with higher fundamental frequencies than adults. However, our results do not support the previously suggested hypothesis that juvenile ground squirrels conceal information regarding their age in their alarm calls because we found significant differences in alarm calls of juveniles and adults. PMID- 26152314 TI - Inpatient versus outpatient vincristine, dactinomycin, and cyclophosphamide for pediatric cancers: Quality and cost implications. AB - BACKGROUND: Approximately 18% of the United States' gross domestic product is attributed to healthcare expenditures. Several studies have illustrated that shifting healthcare from the inpatient to the outpatient setting is more cost effective, in addition to improving patient satisfaction. Vincristine, dactinomycin, and cyclophosphamide (VAC) are used together to treat children with solid tumors. Our traditional treatment approach included a two day inpatient admission. The purpose of this project was to establish a process for the administration of VAC in the outpatient setting to improve satisfaction, and reduce costs. PROCEDURE: We aimed to benchmark practice standards with other institutions, revised our treatment approach to permit outpatient administration, and implemented the new protocol in a stepwise manner. We collected caregiver satisfaction metrics through the use of surveys. Costs of encounters were obtained from administrative data. Total costs and costs by service type were compared using descriptive and mean comparisons. RESULTS: Seven patients received a total of 31 cycles of VAC in the outpatient setting. The time to achieve an appropriate pre-chemotherapy specific gravity was reduced by a median of 120 min. In addition, time spent in the hospital setting was reduced by a mean of 27.2 hr. Adverse effects were minimal and all caregivers reported greater satisfaction with the outpatient regimen. Outpatient administration of VAC was $3,300 less on average compared to the inpatient administration. CONCLUSION: Outpatient VAC provides a safe alternative for administration that reduces healthcare costs, reduces healthcare utilization, and improves patient satisfaction. PMID- 26152315 TI - Large maculopapular cutaneous lesions are associated with favorable outcome in childhood-onset mastocytosis. AB - BACKGROUND: Mastocytosis, characterized by pathologic accumulation of mast cells, can manifest itself in adulthood or childhood. Pediatric patients usually have cutaneous mastocytosis (CM) with mast cell infiltrates limited to the skin and spontaneous improvement of skin lesions after several years. However, there are some patients with persistent disease resembling adulthood-onset mastocytosis. OBJECTIVE: The current classification of CM differentiates between 3 subforms. In clinical practice we noticed that different variants of these subforms might exist, particularly in patients with childhood-onset mastocytosis. Therefore, in the present study, we aimed to investigate whether specific cutaneous lesions in patients with childhood-onset mastocytosis are associated with other disease parameters. METHODS: We analyzed 144 patients with a disease onset of less than age 17 years using a systematic dermatologic approach. RESULTS: One hundred twenty-two patients presented with maculopapular cutaneous mastocytosis (MPCM), 12 patients presented with diffuse CM, and 10 patients presented with solitary mastocytoma of the skin. Patients with MPCM showed particularly heterogeneous cutaneous lesions and were therefore grouped into 3 variants presenting either with small lesions (MPCM-small, skin lesions <1 cm in diameter; n = 19), large lesions (MPCM-large, skin lesions >= 1 cm in diameter; n = 89), or atypical lesions (MPCM-other, n = 14). Patients with MPCM-large lesions, compared with those with MPCM-small lesions, were characterized by significantly lower tryptase levels, shorter disease duration, and earlier disease onset. In addition, more patients with MPCM-large lesions exhibited spontaneous regression of cutaneous lesions. CONCLUSION: Our data show that patients with MPCM-large lesions compared with those with MPCM-small lesions have a more favorable disease course and suggest exploring the size of cutaneous lesions as a prognostic parameter in childhood-onset MPCM. PMID- 26152316 TI - Fish and polyunsaturated fat intake and development of allergic and nonallergic rhinitis. AB - BACKGROUND: Rhinitis is one of the most common diseases in childhood. Fish, polyunsaturated fatty acid (PUFA), and vitamin D intakes have been hypothesized to affect the risk of allergic disease; however, it is unclear whether these are linked to the development of rhinitis. OBJECTIVE: We sought to assess potential associations between consumption of fish, dietary n-3 and n-6 PUFAs, and vitamin D at age 8 years and development of allergic rhinitis (AR) and nonallergic rhinitis (NAR) between the ages of 8 and 16 years. METHODS: We included 1970 participants from a birth cohort. Data on dietary intake was obtained from a food frequency questionnaire at age 8 years. The rhinitis definition was based on questionnaires and IgE measures. RESULTS: The prevalence of rhinitis symptoms at age 8 years was 19% (n = 380). Among the 1590 children without rhinitis symptoms at age 8 years, 21% (n = 337) had AR between ages 8 and 16 years, and 15% (n = 236) had NAR. Regular intake of oily fish and higher long-chain n-3 PUFA intake were associated with a reduced risk of cumulative incidence of NAR (adjusted odds ratio, 0.52 [95% CI, 0.32-0.87] for oily fish; odds ratio, 0.45 [95% CI, 0.30 0.67] for highest vs lowest tertile of long-chain n-3 PUFAs; P trend < .001). The results for rhinitis, irrespective of AR and NAR, were in line with the findings for NAR. CONCLUSION: Regular consumption of oily fish and dietary long-chain n-3 PUFAs in childhood might decrease the risk of rhinitis, especially NAR, between the ages of 8 and 16 years. PMID- 26152317 TI - Metabolomic profiling of asthma and chronic obstructive pulmonary disease: A pilot study differentiating diseases. AB - BACKGROUND: Differentiating asthma from other causes of chronic airflow limitation, such as chronic obstructive pulmonary disease (COPD), can be difficult in a typical outpatient setting. The inflammation of asthma typically is different than that of COPD, and the degree of inflammation and cellular damage varies with asthma severity. Metabolomics is the study of molecules created by cellular metabolic pathways. OBJECTIVES: We hypothesized that the metabolic activity of adults with asthma would differ from that of adults with COPD. Furthermore, we hypothesized that nuclear magnetic resonance spectroscopy (NMR) would measure such differences in urine samples. METHODS: Clinical and urine-based NMR data were collected on adults meeting the criteria of asthma and COPD before and after an exacerbation (n = 133 and 38, respectively) and from patients with stable asthma or COPD (n = 54 and 23, respectively). Partial least squares discriminant analysis was performed on the NMR data to create models of separation (86 metabolites were measured per urine sample). Some subjects' metabolomic data were withheld from modeling to be run blindly to determine diagnostic accuracy. RESULTS: Partial least-squares discriminant analysis of the urine NMR data found unique differences in select metabolites between patients with asthma and those with COPD seen in the emergency department and even in follow-up after exacerbation. By using these select metabolomic profiles, the model could correctly diagnose blinded asthma and COPD with greater than 90% accuracy. CONCLUSION: This is the first report showing that metabolomic analysis of human urine samples could become a useful clinical tool to differentiate asthma from COPD. PMID- 26152319 TI - Open letter to clinicians and pharmacists from Berkeley Phillips, UK medical director, and Seema Patel, established pharma medical director, Pfizer UK. PMID- 26152318 TI - Single B-cell deconvolution of peanut-specific antibody responses in allergic patients. AB - BACKGROUND: The frequencies, cellular phenotypes, epitope specificity, and clonal diversity of allergen-specific B cells in patients with food allergy are not fully understood but are of major pathogenic and therapeutic significance. OBJECTIVE: We sought to characterize peanut allergen-specific B-cell populations and the sequences and binding activities of their antibodies before and during immunotherapy. METHODS: B cells binding fluorescently labeled Ara h 1 or Ara h 2 were phenotyped and isolated by means of flow cytometric sorting from 18 patients at baseline and 13 patients during therapy. Fifty-seven mAbs derived from allergen-binding single B cells were evaluated by using ELISA, Western blotting, and peptide epitope mapping. Deep sequencing of the B-cell repertoires identified additional members of the allergen-specific B-cell clones. RESULTS: Median allergen-binding B-cell frequencies were 0.0097% (Ara h 1) or 0.029% (Ara h 2) of B cells in baseline blood from allergic patients and approximately 3-fold higher during immunotherapy. Five of 57 allergen-specific cells belonged to clones containing IgE-expressing members. Almost all allergen-specific antibodies were mutated, and binding to both conformational and linear allergen epitopes was detected. Increasing somatic mutation of IgG4 members of a clone was seen in immunotherapy, whereas IgE mutation levels in the clone did not increase. CONCLUSION: Most peanut allergen-binding B cells isolated by means of antigen specific flow sorting express mutated and isotype-switched antibodies. Immunotherapy increases their frequency in the blood, and even narrowly defined allergen epitopes are recognized by numerous distinct B-cell clones in a patient. The results also suggest that oral immunotherapy can stimulate somatic mutation of allergen-specific IgG4. PMID- 26152320 TI - Differential cardiovascular and hypothalamic pituitary response to amphetamine in male pathological gamblers versus healthy controls. AB - Cardiovascular and hypothalamic pituitary axis (HPA) disturbances have been observed in individuals who are pathological gamblers (PGs). These may partly derive from chronic exposure to gambling. Response to amphetamine (AMPH) may reveal such disturbances while controlling for differential conditioned responses to gambling in PGs vs healthy controls (HCs). This study assessed heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) and plasma cortisol following oral AMPH (0.4 mg/kg) in male PGs (n=12) and HCs (n=11) who underwent a positron emission tomography (PET) scan. The Stop Signal Task enabled assessment of the link between physiological and behavioral dysregulation. Trait moderating effects were explored. The responses of PGs to AMPH differed from those of HCs on every index. PGs displayed persistent elevation in DBP and concomitant reduction in HR (i.e. baroreflex) compared to HCs beyond 90 min post dose. PGs displayed deficits in cortisol compared to HCs that were partially reversed by AMPH. Impairment on the Stop Signal Task correlated positively with HR in controls, but negatively with HR in PGs, suggesting that strong initial and compensatory cardiac responses to a stimulant may each predict disinhibition. Extraversion predicted greater disinhibition in PGs. Noradrenergic disturbances may contribute to sensitized responses to stimulant challenge and disinhibition in PGs. PMID- 26152321 TI - Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe. AB - Ketamine produces effects in healthy humans that resemble the positive, negative and cognitive symptoms of schizophrenia. We investigated the effect of ketamine administration on brain activity as indexed by blood-oxygen-level-dependent (BOLD) signal change response, and its relationship to ketamine-induced subjective changes, including perceptual distortion. Thirteen healthy participants volunteered for the study. All underwent a 15-min functional MRI acquisition with a ketamine infusion commencing after 5 min (approx 0.26 mg/kg over 20s followed by an infusion of approx. 0.42 mg/kg/h). Following the scan, participants self-rated ketamine-induced effects using the Psychotomimetic States Inventory. Ketamine led to widespread cortical and subcortical increases in BOLD response (FWE-corrected p < 0.01). Self-rated perceptual distortions and delusional thoughts correlated with increased BOLD response in the paracentral lobule (FWE-corrected p < 0.01). The findings suggest that BOLD increases in parietal cortices reflect ketamine effects on circuits that contribute to its capacity to produce perceptual alterations and delusional interpretations. PMID- 26152322 TI - No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder--a randomized, double-blind, placebo-controlled, crossover study. AB - BACKGROUND: Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. METHODS: All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. RESULTS: We did not find any differences in the frequency and the intensity of post-traumatic stress disorder related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. CONCLUSIONS: Our results do not show any effect of the hydrocortisone administration on intrusions in complex post traumatic stress disorder. PMID- 26152323 TI - Antidepressants with a high serotonin reuptake transporter affinity and serum lipid levels in a population-based study in older adults. AB - OBJECTIVE: We aimed to investigate the association between antidepressants and serum lipid levels in a population-based study in older adults. METHODS: We included participants from the prospective Rotterdam Study with data on lipid levels (total, low-density lipoprotein (LDL) and high-density lipoprotein cholesterol, and triglycerides). We classified antidepressants based on binding affinity to the serotonin transporter (low/intermediate- and high-affinity antidepressants). We compared lipid levels in users of these groups of antidepressants with lipid levels in non-users. Furthermore, we studied effect modification by the 102 C>T polymorphism (HTR2A gene), which is associated with antidepressant drug response and metabolic outcomes. RESULTS: Compared with non users (N = 6438), LDL cholesterol level was higher (2.9 versus 3.1 mmol/L, respectively; p = 0.05) in users of high-affinity antidepressants (N = 89). Similar levels of the other lipids were observed between the groups for the other lipids. The mean difference in serum LDL cholesterol level between non-users and users of high-affinity antidepressants was largest in participants with the CC genotype compared with the other genotypes (notably 0.47 mmol/L), indicative of effect modification (p-value for interaction = 0.03). CONCLUSION: Antidepressants with a high serotonin reuptake transporter affinity were associated with higher LDL cholesterol levels, which were modified by a common genetic variation in the HTR2A gene. PMID- 26152324 TI - Prevalence and predictors of alcohol use during pregnancy: findings from international multicentre cohort studies. AB - OBJECTIVES: To compare the prevalence and predictors of alcohol use in multiple cohorts. DESIGN: Cross-cohort comparison of retrospective and prospective studies. SETTING: Population-based studies in Ireland, the UK, Australia and New Zealand. PARTICIPANTS: 17,244 women of predominantly Caucasian origin from two Irish retrospective studies (Growing up in Ireland (GUI) and Pregnancy Risk Assessment Monitoring System Ireland (PRAMS Ireland)), and one multicentre prospective international cohort, Screening for Pregnancy Endpoints (SCOPE) study. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of alcohol use pre pregnancy and during pregnancy across cohorts. Sociodemographic factors associated with alcohol consumption in each cohort. RESULTS: Alcohol consumption during pregnancy in Ireland ranged from 20% in GUI to 80% in SCOPE, and from 40% to 80% in Australia, New Zealand and the UK. Levels of exposure also varied substantially among drinkers in each cohort ranging from 70% consuming more than 1-2 units/week in the first trimester in SCOPE Ireland, to 46% and 15% in the retrospective studies. Smoking during pregnancy was the most consistent predictor of gestational alcohol use in all three cohorts, and smokers were 17% more likely to drink during pregnancy in SCOPE, relative risk (RR)=1.17 (95% CI 1.12 to 1.22), 50% more likely to drink during pregnancy in GUI, RR=1.50 (95% CI 1.36 to 1.65), and 42% more likely to drink in PRAMS, RR=1.42 (95% CI 1.18 to 1.70). CONCLUSIONS: Our data suggest that alcohol use during pregnancy is prevalent and socially pervasive in the UK, Ireland, New Zealand and Australia. New policy and interventions are required to reduce alcohol prevalence both prior to and during pregnancy. Further research on biological markers and conventions for measuring alcohol use in pregnancy is required to improve the validity and reliability of prevalence estimates. PMID- 26152325 TI - Occurrence and determinants of selective reporting of clinical drug trials: design of an inception cohort study. AB - INTRODUCTION: Responsible conduct of research implies that results of clinical trials should be completely and adequately reported. This article describes the design of a cohort study that aims to investigate the occurrence and the determinants of selective reporting in an inception cohort of all clinical drug trials that were reviewed by the Dutch Institutional Review Boards (IRBs) in 2007. It also describes the characteristics of the study cohort. METHODS AND ANALYSIS: In 2007, Dutch IRBs reviewed 622 clinical drug trials. For each trial, we assessed the stages of progress. We discriminated five intermediate stages and five definite stages. Intermediate stages of progress are: approved by an IRB; started inclusion; completed as planned; terminated early; published as article. The definite stages of progress are: rejected by an IRB; never started inclusion; not published as article; completely reported; selectively reported. We will use univariate and multivariate Cox regression models to identify trial characteristics associated with non-publication. We will identify seven trial specific discrepancy items, including the objectives, inclusion and exclusion criteria, end points, sample size, additional analyses, type of population analysis and sponsor acknowledgement. The percentage of trials with discrepancies between the protocol and the publication will be scored. We will investigate the association between trial characteristics and the occurrence of discrepancies. ETHICS AND DISSEMINATION: No IRB-approval is required for this study. Access to confidential research protocols was provided by the Central Committee on Research Involving Human Subjects. We plan to finish data collection in June 2015, and expect to complete data cleaning, analysis and manuscript preparation within the next 3 months. Hence, a first draft of an article containing the results is expected before the end of October 2015. PMID- 26152326 TI - Efficacy of a minimal home-based psychoeducative intervention versus usual care for managing anxiety and dyspnoea in patients with severe chronic obstructive pulmonary disease: a randomised controlled trial protocol. AB - INTRODUCTION: In its final stages, chronic obstructive pulmonary disease is a severely disabling condition that is characterised by dyspnoea, which causes substantial anxiety. Anxiety is associated with an impaired quality of life and increased hospital admissions. Untreated comorbid anxiety can have devastating consequences for both patients and their relatives. Non-pharmacological interventions, including cognitive-behavioural therapy, have been effective in managing anxiety and dyspnoea in patients with chronic obstructive pulmonary disease. However, the majority of existing interventions have tested the efficacy of relatively intensive comprehensive programmes and primarily targeted patients who have moderate pulmonary disease. We present the rationale and design for a trial that focused on addressing the challenges experienced by severe pulmonary disease populations. The trial investigates the efficacy of a minimal home-based psychoeducative intervention versus usual care for patients with severe chronic obstructive pulmonary disease. METHODS AND ANALYSIS: The trial is a randomised controlled trial with a 4-week and 3-month follow-up. 66 patients with severe chronic obstructive pulmonary disease and associated anxiety will be randomised 1:1 to either an intervention or control group. The intervention consists of a single psychoeducative session in the patient's home in combination with a telephone booster session. The intervention is based on a manual, with a theoretical foundation in cognitive-behavioural therapy and psychoeducation. The primary outcome is patient-reported anxiety as assessed by the Hospital and Anxiety and Depression Scale (HADS). ETHICS AND DISSEMINATION: This trial complies with the latest Declaration of Helsinki, and The Ethics Committee of the Capital Region of Denmark (number H-1-2013-092) was queried for ethical approval. Trial results will be disseminated in peer-reviewed publications and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT02366390. PMID- 26152327 TI - Anti-N-methyl-D-aspartate receptor encephalitis concomitant with multifocal subcortical white matter lesions on magnetic resonance imaging: a case report and review of the literature. AB - BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is a severe autoimmune disorder characterized by severe psychiatric symptoms, seizures, decreased consciousness, autonomic dysregulation, and dyskinesias. Multifocal subcortical white matter lesions on fluid-attenuated inversion recovery and diffuse weighted images have rarely been reported in previous literature, and serial magnetic resonance imaging changes after plasma exchange have not been presented before. CASE PRESENTATION: A previously healthy 24-year-old Chinese woman presented with acute psychiatric symptoms characterized by fear and agitation followed by decreased consciousness, dyskinesias, and seizures. Magnetic resonance imaging revealed hyperintense lesions on fluid-attenuated inversion recovery and diffuse weighted images in bilateral subcortical white matter. Cerebrospinal fluid analysis revealed a mild pleocytosis with lymphocytic predominance. Protein and glucose levels were normal. Aquaporin-4 antibodies in serum and cerebrospinal fluid were negative. Identification of anti-N-methyl-D aspartate receptor antibodies in serum and cerebrospinal fluid confirmed the diagnosis of anti-N-methyl-D-aspartate receptor encephalitis. She was initially treated with combined intravenous immunoglobulin and methylprednisolone without improvement. Plasma exchange was then initiated with good response; the patient made a full recovery after several cycles of plasma exchange. Repeat magnetic resonance imaging performed 1 month after plasma exchange showed partial resolution of the hyperintense lesions in bilateral subcortical white matter, and follow-up magnetic resonance imaging 2 months after plasma exchange showed complete resolution. CONCLUSION: Anti-N-methyl-D-aspartate receptor encephalitis may be concomitant with multifocal subcortical white matter lesions. Such lesions may resolve after appropriate immunotherapy. PMID- 26152328 TI - Editorial Comment to Possible pathophysiology of ketamine-related cystitis and associated treatment strategies. PMID- 26152330 TI - Factors that influence mother-child reunification for mothers with a history of substance use: A systematic review of the evidence to inform policy and practice in Australia. AB - BACKGROUND: An estimated 60-70% of Australian children in out of home care have a parent with a substance use disorder (SUD). The assessment of a parent's history and needs and the design of supportive interventions, particularly for mothers who are often the primary carers of children, are important considerations in deciding whether or not family reunification is desirable and possible. It is not clear from the research how the needs of families can be best met. There are no systematic reviews that provide evidence to inform the development of preventative and remedial interventions and related policy options. We undertook a systematic review to examine maternal characteristics and program features that facilitate or pose a barrier to mother-child reunification in contexts where mothers have a SUD. METHODS: A structured search of nine databases was undertaken to identify peer reviewed literature in English between 2004 and 2014 and examine factors that influenced mother-child reunification in mothers with SUD. We employed a narrative synthesis design to analyse the findings sections of all papers as the methods of the various studies did not permit the pooling of data. RESULTS: A total of 11 studies were included in this review. Findings show that factors such as timeliness of treatment entry, treatment completion and the receipt of matched services, and programs that provided a greater level of integrated care are positively related to reunification. The presence of a mental health disorder, use of opiates and having a greater number of children were barriers to reunification. CONCLUSION: Women with SUD who have a child in out of home care appear to have multiple unmet needs. Accessible, stigma free and comprehensive integrated care services, as well as greater access to primary health care that address social and medical issues must be considered to improve the physical and psycho-social outcomes of these women and their children. PMID- 26152329 TI - Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson's disease. AB - Impairments of action language have been documented in early stage Parkinson's disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxel-based morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies. PMID- 26152331 TI - Significant stabilization of palladium by gold in the bimetallic nanocatalyst leading to an enhanced activity in the hydrodechlorination of aryl chlorides. AB - The stabilization effect of Au towards Pd changed the reactivity of Pd in Au/Pd bimetallic nanoclusters, altering the reaction mechanism from homogeneous to heterogeneous in dechlorination reaction of aryl chlorides. This phenomenon was illustrated by the observed enhancement of the rate of reaction by in situ generated Au-rich bimetallic Au/Pd nanoclusters. PMID- 26152332 TI - Neochlorogenic Acid Inhibits Lipopolysaccharide-Induced Activation and Pro inflammatory Responses in BV2 Microglial Cells. AB - Microglia is the resident innate immune cells that sense pathogens and tissue injury in the central nervous system. Microglia becomes activated in response to injury, infection, and other stimuli that threaten neuronal survival. Microglia activation plays an important role in neurodegenerative diseases. Neochlorogenic acid (NCA) is a natural polyphenolic compound found in dried fruits and other plants. Although previous studies have shown that phenolic acids including NCA have outstanding antioxidant, antibacterial, antiviral, and antipyretic activities, there has not yet been investigated for anti-inflammatory effects. Therefore, for the first time we have examined the potential of NCA to inhibit microglial activation and pro-inflammatory responses in the brain. We found that lipopolysaccharide-induced inducible nitric oxide synthase, and cyclooxygenase-2 expression, and nitric oxide formation was suppressed by NCA in a dose-dependent manner in BV2 microglia. NCA also inhibited the production of pro-inflammatory mediators, tumor necrosis factor-alpha and interleukin-1 beta. Furthermore, phosphorylated nuclear factor-kappa B p65 and p38 mitogen-activated protein kinase activation were blocked by NCA. Taken together, these results suggest that NCA exerts neuroprotective effects through the inhibition of pro-inflammatory pathways in activated microglia. PMID- 26152333 TI - Analysis of the CHCHD10 gene in patients with frontotemporal dementia and amyotrophic lateral sclerosis from Spain. PMID- 26152334 TI - ST-segment elevation on intracoronary electrocardiogram after percutaneous coronary intervention is associated with worse outcome in patients with non-ST segment elevation myocardial infarction. AB - OBJECTIVES: We sought to examine whether intracoronary electrocardiogram (IC-ECG) assessment in patients with non-ST-segment elevation myocardial infarction (NSTEMI) can predict cardiac outcomes. BACKGROUND: There has been no data correlating myocardial damage and cardiac events with an IC-ECG ST-segment change after percutaneous coronary intervention (PCI) in NSTEMI patients. METHODS: We examined 111 NSTEMI patients undergoing PCI with an IC-ECG recording. IC-ECG ST segment elevation (STE) was defined as >0.1 mV in the risk area, located by placing the guidewire distal to the culprit lesion. Clinical characteristics and in-hospital and long-term follow-up adverse cardiac event rates were compared between IC-ECG STE and non-IC-ECG STE groups at the completion of PCI. RESULTS: IC-ECG STE was observed in 36 patients (32.4%) immediately after PCI. Peak cardiac biomarkers were significantly elevated in patients with IC-ECG STE versus those without (cardiac troponin I 31.9 ng/mL (18.0-104.5) vs. 8.2 ng/mL (1.8 21.4); P < 0.001). At a median follow-up of 35 months, the cardiac event free rate was significantly worse in patients with IC-ECG STE than in those without (long-rank test chi(2) = 10.9; P = 0.001). Cox proportional hazards analysis showed IC-ECG STE (hazard ratio, 2.54; 95% confidence interval [CI], 1.38-4.70; P = 0.003) was an independent predictors of cardiac events. CONCLUSIONS: The present study suggests that presence of IC-ECG STE might help identify high-risk NSTEMI patients with greater myocardial injury leading to adverse cardiac events. PMID- 26152335 TI - Eosinophils in lichen sclerosus et atrophicus. AB - BACKGROUND: The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis. METHODS: A retrospective review of the histopathology and medical records of 235 patients with LS who were evaluated from June 1992 to June 2012 was performed. RESULTS: Sixty-nine patients (29%) had eosinophils on histopathology. Among patients with associated diseases, a statistically significant association between the eosinophil cohort and the cohort without eosinophils was not detected. CONCLUSIONS: The importance of eosinophils is uncertain, but our data suggest that the finding of tissue eosinophils alone is not sufficient to prompt an extensive workup for additional diagnoses. PMID- 26152337 TI - Polymorphisms in the precursor microRNAs and aflatoxin B1-related hepatocellular carcinoma. AB - The altered expression of some microRNAs (miRNAs) is observed in hepatocellular carcinoma (HCC); however, the genetic polymorphisms in the precursor miRNAs (pre miRNAs) in aflatoxin B1 (AFB1)-related HCC have not yet been investigated. A hospital-based case-control study, including 1,706 HCC cases and 2,270 controls without any liver diseases or tumors, was conducted in a high AFB1 exposure area of China to assess the relationship between 48 polymorphisms in the pre-miRNAs and AFB1-related HCC risk and prognosis. Among 48 polymorphisms, only rs28599926 (in the miRNA 1268a) affected HCC risk. Compared with the homozygote of rs28599926C alleles (rs28599926-CC), the genotypes of rs28599926 T alleles (namely rs28599926-CT or -TT) increased HCC risk (odds ratio [OR]: 1.63 and 5.52, 95% confidence interval [CI]: 1.40-1.90 and 4.27-7.14, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. This polymorphism was associated not only with larger tumor size, higher portal vein tumor risk, and tumor dedifferentiation, but also with higher AFB1 adducts levels and increasing the mutation risk of TP53 gene. Furthermore, rs28599926 modified the tumor recurrence free survival (hazard ratio [HR]: 2.86, 95% CI: 2.36-3.43) and overall survival (HR: 2.12, 95% CI: 1.86-2.41) of cases. Additionally, one target of miR-1268a was show to be the ADAMTS4 mRNA and rs28599926 polymorphism might modify ADAMTS4 expression. These findings indicate that polymorphisms in the pre-miRNAs may be risk and prognostic biomarkers of AFB1-related HCC, and rs28599926 in miR-1268a is such a potential candidate. (c) 2015 Wiley Periodicals, Inc. PMID- 26152336 TI - Identification of large variation in pfcrt, pfmdr-1 and pfubp-1 markers in Plasmodium falciparum isolates from Ethiopia and Tanzania. AB - BACKGROUND: Plasmodium falciparum resistance to anti-malarials is a major drawback in effective malaria control and elimination globally. Artemisinin combination therapy (ACT) is currently the key first-line treatment for uncomplicated falciparum malaria. Plasmodium falciparum genetic signatures at pfmdr-1, pfcrt, and pfubp-1 loci are known to modulate in vivo and in vitro parasite response to ACT. The objective of this study was to assess the distribution of these resistance gene markers in isolates collected from different malaria transmission intensity in Ethiopia and Tanzania. METHODS: Plasmodium falciparum clinical isolates were collected from different regions of Ethiopia and Tanzania. Genetic polymorphisms in the genes pfcrt, pfmdr-1 and pfubp-1 were analysed by PCR and sequencing. Frequencies of the different alleles in the three genes were compared within and between regions, and between the two countries. RESULTS: The majority of the isolates from Ethiopia were mutant for the pfcrt 76 and wild-type for pfmdr-1 86. In contrast, the majority of the Tanzanian samples were wild-type for both pfcrt and pfmdr-1 loci. Analysis of a variable linker region in pfmdr-1 showed substantial variation in isolates from Tanzania as compared to Ethiopian isolates that had minimal variation. Direct sequencing of the pfubp-1 region showed that 92.8% (26/28) of the Ethiopian isolates had identical genome sequence with the wild type reference P. falciparum strain 3D7. Of 42 isolates from Tanzania, only 13 (30.9%) had identical genome sequences with 3D7. In the Tanzanian samples, 10 variant haplotypes were identified. CONCLUSION: The majority of Ethiopian isolates carried the main marker for chloroquine (CQ) resistance, while the majority of the samples from Tanzania carried markers for CQ susceptibility. Polymorphic genes showed substantially more variation in Tanzanian isolates. The low variability in the polymorphic region of pfmdr-1 in Ethiopia may be a consequence of low transmission intensity as compared to high transmission intensity and large variations in Tanzania. PMID- 26152338 TI - Relationships among cleaning, environmental DNA, and healthcare-associated infections in a new evidence-based design hospital. AB - OBJECTIVE: Hospital environments influence healthcare-associated infection (HAI) patterns, but the role of evidenced-based design (EBD) and residual bacterial DNA (previously thought to be clinically inert) remain incompletely understood. METHODS: In a newly built EBD hospital, we used culture-based and culture-free (molecular) assays, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS) to determine: (1) patterns of environmental contamination with target organisms (TOs) and multidrug-resistant (MDR) target organisms (MDR-TOs); (2) genetic relatedness between environmentally isolated MDR-TO and those from HAIs; and (3) correlation between surface contamination and HAIs. RESULTS: A total of 1,273 high-touch surfaces were swabbed before and after terminal cleaning during 77 room visits. Of the 2,546 paired swabs, 47% had cultivable biomaterial and 42% had PCR-amplifiable DNA. The ratios of TOs detected to surfaces assayed were 85 per 1,273 for the culture-based method and 106 per 1,273 for the PCR-based method. Sinks, toilet rails, and bedside tables most frequently harbored biomaterial. Although cleaned surfaces were less likely to have cultivable TOs than precleaned surfaces, they were not less likely to harbor bacterial DNA. The rate of MDR-TOs to surfaces swabbed was 0.1% (3/2546). Although environmental MDR-TOs and MDR-TOs from HAIs were genetically related by PFGE, WGS revealed that they were unrelated. Environmental levels of cultivable Enterococcus spp. and E. coli DNA were positively correlated with infection incidences (P<.04 and P<.005, respectively). CONCLUSION: MDR-TOs were rarely detected during surveillance and were not implicated in HAIs. The roles of environmental DNA and EBD, particularly with respect to water-associated fixtures or the potential suppression of cultivable environmental MDR-TOs, warrant multicenter investigations. PMID- 26152339 TI - The pediatric hematology/oncology educational laboratory in-training examination (PHOELIX): A formative evaluation of laboratory skills for Canadian pediatric hematology/oncology trainees. AB - BACKGROUND: Pediatric hematologists/oncologists need to be skilled clinicians, and must also be adept and knowledgeable in relevant areas of laboratory medicine. Canadian training programs in this subspecialty have a minimum requirement for 6 months of training in acquiring "relevant laboratory diagnostic skills." The Canadian pediatric hematology/oncology (PHO) national specialty society, C17, recognized the need for an assessment method in laboratory skills for fellows graduating from PHO training programs. PROCEDURE: Canadian pediatric hematologists/oncologists were surveyed regarding what were felt to be the essential laboratory-related knowledge and skills deemed necessary for graduating pediatric hematology/oncology trainees. The PHOELIX (Pediatric hematology/oncology educational laboratory in-training examination) was then developed to provide an annual formative evaluation of laboratory skills in Canadian PHO trainees. RESULTS: The majority of PHO respondents (89%) felt that laboratory skills are important in clinical practice. An annual formative examination including review of glass slides was implemented starting in 2010; this provides feedback regarding knowledge of laboratory medicine to both trainees and program directors (PDs). CONCLUSIONS: We have successfully created a formative examination that can be used to evaluate and educate trainees, as well as provide PDs with a tool to gauge the effectiveness of their laboratory training curriculum. Feedback has been positive from both trainees and PDs. PMID- 26152340 TI - End of life decision planning in the perioperative setting: the elephant in the room? PMID- 26152341 TI - Decrease in pulse pressure and stroke volume variations after mini-fluid challenge accurately predicts fluid responsiveness?. AB - BACKGROUND: Dynamic indices, such as pulse pressure variation (PPV), are inaccurate predictors of fluid responsiveness in mechanically ventilated patients with low tidal volume. This study aimed to test whether changes in continuous cardiac index (CCI), PPV, and stroke volume variation (SVV) after a mini-fluid challenge (100 ml of fluid during 1 min) could predict fluid responsiveness in these patients. METHODS: We prospectively studied 49 critically ill, deeply sedated, and mechanically ventilated patients (tidal volume <8 ml kg(-1) of ideal body weight) without cardiac arrhythmias, in whom a fluid challenge was indicated because of circulatory failure. The CCI, SVV (PiCCOTM; Pulsion), and PPV (MP70TM; Philips) were measured before and after 100 ml of colloid infusion during 1 min, and then after the additional infusion of 400 ml during 14 min. Responders were defined as subjects with a >=15% increase in cardiac index (transpulmonary thermodilution) after the full (500 ml) fluid challenge. Areas under the receiver operating characteristic curves (AUCs) and the grey zones were determined for changes in CCI (DeltaCCI100), SVV (DeltaSVV100), and PPV (DeltaPPV100) after 100 ml fluid challenge. RESULTS: Twenty-two subjects were responders. The DeltaCCI100 predicted fluid responsiveness with an AUC of 0.78. The grey zone was large and included 67% of subjects. The DeltaSVV100 and DeltaPPV100 predicted fluid responsiveness with AUCs of 0.91 and 0.92, respectively. Grey zones were small, including <=12% of subjects for both indices. CONCLUSIONS: The DeltaSVV100 and DeltaPPV100 predict fluid responsiveness accurately and better than DeltaCCI100 (PiCCOTM; Pulsion) in patients with circulatory failure and ventilated with low volumes. PMID- 26152344 TI - Lipopolysaccharide challenge significantly influences lipid metabolism and proteome of white adipose tissue in growing pigs. AB - BACKGROUND: White adipose tissue is recognized as a highly active organ, which is closely related to a large number of physiological and metabolic processes besides storing triglycerides. However, little is known regarding the response of adipose tissue to acute inflammation. Therefore, in this study we employed growing pigs to investigate the changes of lipid metabolism and proteome in white adipose tissue after lipopolysaccharide (LPS) stimulation as a model for bacterial infection. METHODS: The expression of lipid metabolism and inflammation related genes was determined by quantitative real-time polymerase chain reaction. Label-free proteomics analysis was used to investigate changes of the protein profile in white adipose tissue and western blot was used to verify changes of selected adipokines. RESULTS: The results indicated that LPS significantly increased the expression of toll-like receptor (TLR) 2/4 pathway-related genes and pro-inflammatory factors. Lipid metabolism related genes, including acetyl CoA carboxylase 1 (ACACA), fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD), uncoupling protein 2 (UCP2), and 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), were down-regulated and the lipolytic enzyme activity was decreased after LPS injection. Proteome analysis revealed 47 distinct proteins with > 2-fold changes. The down-regulation of two proteins (cAMP-dependent protein kinase type II-alpha regulatory subunit and beta-tubulin) has been verified by western blot analysis. In addition, the abundance of two adipokines (adiponectin and zinc-alpha2-glycoprotein) was significantly increased after LPS injection. CONCLUSION: In conclusion, LPS challenge can cause acute inflammation in white adipose tissue. Concurrently, lipid metabolism was significantly suppressed and the abundance of several proteins changed in white adipose tissue. The results provide new clues to understand the adipose dysfunction during inflammation. PMID- 26152345 TI - Multiple consecutive norovirus infections in the first 2 years of life. AB - Studies investigating the magnitude and breath of protective immune responses after primary and subsequent norovirus infections in pediatric populations are limited. We investigated incidence of norovirus infections and serological responses in a child from longitudinal stool and serum samples collected from birth to 2 years of age. Four consecutive infections with distinct genotypes of norovirus were detected. Serum antibodies were genotype-specific offering no protection to reinfection with heterologous virus. CONCLUSION: This study describes norovirus-specific serological responses in a child with four consecutive norovirus infection during the first 2 years of life. The response is type-specific and does not protect from a subsequent infection with a heterologous virus. WHAT IS KNOWN: * Correlates of protection to norovirus infection and disease are not yet determined, and most of the presently available data concern adult population. WHAT IS NEW: * This manuscript describes serological immune responses after primary and subsequent infections in a child during the first 2 years of life. PMID- 26152346 TI - Age-related decrease in mtDNA content as a consequence of mtDNA 4977 bp deletion. AB - As one of the most frequent somatic mutations accumulated during aging in human mitochondrial DNA, the 4977 bp deletion has intrigued scientific interest in recent years. Although many studies have shown a significant increase in the amount of 4977 bp deletion, the findings with respect to an age-dependent escalate of DeltamtDNA4977 bp in blood are still disputatious. Therefore, we investigated the presence of common deletion and mtDNA deletion level in whole blood samples of 100 old individuals (60-90 years). We detected the accumulation of common deletion in 46 old individuals. Consequently, there was statistically significant difference between the aged and young individuals in mitochondrial content (p = 0.01) and deletion levels ranged from 2% to 17% of the total mtDNA (mean: 10% +/- 0.02%). We conclude that common deletion has decreased the mtDNA content; however, it is not clearly detectable in the blood as one of the fast replicating tissues comparing with tissues with low mitotic activity. PMID- 26152347 TI - The complete mitochondrial genome sequence of Acentrogobius sp. (Gobiiformes: Gobiidae) and phylogenetic studies of Gobiidae. AB - At present, few morphological descriptions are available for Acentrogobius species and there exist some confused issues on the species classification and phylogeny. In this study, we first determined and described the complete mitochondrial genome of Acentrogobius sp. The complete mitogenome sequence is 17 083 bp in length, containing 13 protein-coding genes, two rRNA genes, 22 tRNA genes, a putative control region (CR), and a light-strand replication origin (OL). The overall base composition is 28.9% A, 26.2% T, 28.5% C, and 16.4% G, with a slight AT bias (55.1%). To furthermore validate the new determined sequences, phylogenetic trees involving all the Gobiidae species available in GenBank database were constructed. These results are expected to provide useful molecular data for species identification and further phylogenetic studies of Gobiiformes. PMID- 26152348 TI - Complete mitochondrial genome of Sinergasilus polycolpus (Copepoda:Poecilostomatoida). AB - The full mitochondrial (mt) genome of Sinergasilus polycolpus is 14 000 bp in length, and it contains 13 protein-coding genes, 22 transfer RNA genes, 2 rRNA genes and 1 non-coding region. The genome organization, nucleotide composition and codon usage are different compared to other Copepodas, such as Lernaea cyprinacea. The full mt genome of S. polycolpus provides useful information for further studies on epidemiology and phylogenetics. PMID- 26152349 TI - The complete mitochondrial genome sequence of Garrulax ocellatus (Aves, Passeriformes, Timaliidae). AB - Timaliidae, generally known as the babblers, includes about 275 species in 50 genera. We sequenced the complete mitochondrial genome of Garrulax ocellatus, and it was determined to be 17,828 bp in length, containing 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNAsfer (tRNA) genes, and 2 control regions. The complete mitochondrial genome contained 15.24% G, 23.02% T, 33.13% C, and 28.61% A, which was similar to other Passeriformes mitochondrial genomes. There are eight tRNA genes and one PCG (ND6) encoded on the L-strand, and other PCGs were encoded on the H-strand. All genes were closely assembled and only 17 intergenic spacers were observed. In total, the spacers were 99 bp in length, and there were seven pairs of genes overlapping sequences of 30 bp in length. Phylogenetic relationship could provide useful information for the further study on the species taxonomic. PMID- 26152350 TI - The complete mitochondrial genome of Hasora vitta (Butler, 1870) (Lepidoptera: Hesperiidae). AB - The complete mitochondrial genome (mitogenome) of Hasora vitta was sequenced and analyzed in the study. The mitogenome is 15 282 bp in size, including 37 genes and a putative control region. Thirteen protein-coding genes all start with a typical ATN codon, expect that COI gene uses CGA as its initial codon. Majority of the 13 PCGs have a complete termination codon (TAA or TAG) except for COII and ND4 have a single T residue. All tRNAs have typical clover-leaf secondary structure, except for tRNASer((AGN)), in which the dihydrouridine (DHU) arm is a simple loop. In the sampled species of Hesperiidae, Hasora vitta, Choaspes benjaminii, Ampittia dioscorides, the remaining sampled species, Celaenorrhinus maculosus (Daimio tethys, Ctenoptilum vasava), Potanthus flavus (Polytremis nascens, Ochlodes venata), are recovered in phylogenetic analyses with high supports. PMID- 26152351 TI - Complete mitochondrial genome of Cotton Leaf Roller Haritalodes derogata (Lepidoptera: Crambidae). AB - Haritalodes derogata (Lepidoptera: Crambidae) has been recorded as an important pest of cotton in many countries of the world. In this study, the complete mitochondrial (mt) genome of Cotton Leaf Roller Haritalodes derogata is determined, which is 15,253 bp in length (GenBank accession number: KC515397) containing 37 typical animal mitochondrial gene and an A + T-rich region. The gene order of H. derogata mtDNA was different from the insect ancestral gene order in the translocation of trnM, as shared by previously sequenced lepidopteran mtDNAs. The protein-coding genes (PCGs) have typical mitochondrial start codons ATN, with the exception of COI, Nad5, which uses the start codons CGA, GTT. In addition, five of 13 PCGs harbor the incomplete termination codons, a single T. All of the tRNA genes had typical cloverleaf secondary structures except for trnS1(AGN). Like other lepidopteran mtgenomes, the control region is located between rrnS and trnM with a length of 329 bp and an A + T content of 96%, which is the most AT-rich region and habors a conserved structure combining the motif ATAGA and a 14-bp poly-T stretch. Both maximum likelihood and Bayesian inference analyses highly support a sister-group relationship: Pyraustinae + (Spilomelinae + (Acentropina (Crambine + Schoenobiine))). PMID- 26152352 TI - The complete mitochondrial genome of the endemic and threatened killifish Orestias ascotanensis Parenti, 1984 (Cyprinodontiformes, Cyprinodontidae) from the High Andes. AB - The killifish Orestias ascotanensis is endemic to the small isolated springs of Ascotan salt pan in the Central High Andes, Chile. Due to small populations, mining activity, and increasing aridity, this species is catalogued in danger of extinction. The complete mitochondrial genome of O. ascotanesis was assembled with an Ion Torrent sequencer (chip 318) that produced 2.61 million of reads. The 16 617 bp of the entire genome consisted of 22 transfer RNAs, 2 ribosomal RNAs, 13 protein-coding genes, and a control region, showing that the gene composition and arrangement match to that reported for most fishes. PMID- 26152353 TI - A microfluidics approach to study the accumulation of molecules at basal lamina interfaces. AB - For an efficient distribution of drugs and drug carriers through biological barriers such as the vascular system, the size and surface properties of nanoparticles and molecules play a key role. To screen for important parameters which determine the ability of drugs or drug carriers to translocate through complex biological barriers, an in vitro assay which correctly predicts the behavior of those objects in vivo would be highly desirable. Here, we present a microfluidic setup to probe the diffusive spreading of molecules with different net charges and molecular weights through a basal lamina interface - a biopolymer system which contributes to the barrier function of the vascular system and the skin. From our data, we find a charge dependent accumulation of molecules at the gel interface which is consistent with transient binding of those molecules to the gel constituents. We also observe a similar charge-dependent accumulation of molecules in living mice where the test molecules colocalize with collagen IV, a key component of the basal lamina. Our assay may serve as a platform to perform penetration experiments with even more complex interfaces combining cellular barriers with biopolymer coatings. PMID- 26152354 TI - Non-polar lipids characterization of Quinoa (Chenopodium quinoa) seed by comprehensive two-dimensional gas chromatography with flame ionization/mass spectrometry detection and non-aqueous reversed-phase liquid chromatography with atmospheric pressure chemical ionization mass spectrometry detection. AB - A chemical characterization of major lipid components, namely, triacylglycerols, fatty acids and the unsaponifiable fraction, in a Quinoa seed lipids sample is reported. To tackle such a task, non-aqueous reversed-phase high-performance liquid chromatography with mass spectrometry detection was employed. The latter was interfaced with atmospheric pressure chemical ionization for the analysis of triacylglycerols. The main triacylglycerols (>10%) were represented by OLP, OOL and OLL (P = palmitoyl, O = oleoyl, L = linoleoyl); the latter was present in the oil sample at the highest percentage (18.1%). Furthermore, fatty acid methyl esters were evaluated by gas chromatography with flame ionization detection. 89% of the total fatty acids was represented by unsaturated fatty acid methyl esters with the greatest percentage represented by linoleic and oleic acids accounting for approximately 48 and 28%, respectively. An extensive characterization of the unsaponifiable fraction of Quinoa seed lipids was performed for the first time, by using comprehensive two-dimensional gas chromatography with dual mass spectrometry/flame ionization detection. Overall, 66 compounds of the unsaponifiable fraction were tentatively identified, many constituents of which (particularly sterols) were confirmed by using gas chromatography with high resolution time-of-flight mass spectrometry. PMID- 26152355 TI - In Vivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors. AB - Reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Up regulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus, targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here, we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient-derived pancreatic xenograft model. Lentiviruses expressing short hairpin RNAs (shRNAs) targeting 12 different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times, and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including carbonic anhydrase IX (CAIX), monocarboxylate transporter 4, and anionic amino acid transporter light chain, xc- system (xCT) were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation because shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient-derived pancreatic tumor model. PMID- 26152356 TI - Smac Mimetic-Induced Upregulation of CCL2/MCP-1 Triggers Migration and Invasion of Glioblastoma Cells and Influences the Tumor Microenvironment in a Paracrine Manner. AB - Second mitochondria-derived activator of caspase (Smac) mimetics are considered as promising anticancer therapeutics that are currently under investigation in early clinical trials. They induce apoptosis by antagonizing inhibitor of apoptosis proteins, which are frequently overexpressed in cancer. We previously reported that Smac mimetics, such as BV6, additionally exert non-apoptotic functions in glioblastoma (GBM) cells by stimulating migration and invasion in a nuclear factor kappa B (NF-kappaB)-dependent manner. Because NF-kappaB target genes mediating these effects are largely unknown, we performed whole-genome expression analyses. Here, we identify chemokine (C-C motif) ligand 2 (CCL2) as the top-listed NF-kappaB-regulated gene being upregulated upon BV6 treatment in GBM cells. BV6-induced upregulation and secretion of CCL2 are required for migration and invasion of GBM cells because knockdown of CCL2 in GBM cells abolishes these effects. Co-culture experiments of GBM cells with non-malignant astroglial cells reveal that BV6-stimulated secretion of CCL2 by GBM cells into the supernatant triggers migration of astroglial cells toward GBM cells because CCL2 knockdown in BV6-treated GBM cells impedes BV6-stimulated migration of astroglial cells. In conclusion, we identify CCL2 as a BV6-induced NF-kappaB target gene that triggers migration and invasion of GBM cells and exerts paracrine effects on the GBM's microenvironment by stimulating migration of astroglial cells. These findings provide novel insights into the biological functions of Smac mimetics with important implications for the development of Smac mimetics as cancer therapeutics. PMID- 26152357 TI - Platelet-Synthesized Testosterone in Men with Prostate Cancer Induces Androgen Receptor Signaling. AB - Platelets have been long postulated to play a critical role in the pathogenesis of prostate cancer, although relatively little is known regarding the precise mechanisms involved. Androgen deprivation therapy (ADT) for prostate cancer eventually fails with relapse occurring in the form of castration-resistant prostate cancer (CRPC). CRPC tumors typically overexpress androgen receptor (AR), demonstrating continued dependence upon AR signaling. Platelets have been previously demonstrated to contain androgens, and we sought to explore the contribution of platelet-derived androgens in CRPC. In this study, we examined the role of platelet-derived androgens in vitro using platelets from men with CRPC, men with high-risk prostate cancer, and healthy male donors. A series of in vitro assays was performed to elucidate the impact of platelet-derived androgens on androgen-sensitive prostate tumor cells. By examining platelet-derived androgen effects on AR signaling in prostate tumor cells, we found that platelets, from men with CRPC and on ADT, strongly induce AR target genes and tumor cell proliferation. Moreover, we show a fully intact testosterone (T) biosynthetic pathway within platelets from its precursor cholesterol and demonstrate that platelets of CRPC patients with ADT resistance are able to generate T. Overall, our findings reveal an unknown capacity of platelets to synthesize T at functionally relevant levels in patients with lethal prostate cancer. Importantly, it suggests a novel paracrine mechanism of T production that may act to sustain CRPC state and potentiate therapeutic resistance. PMID- 26152358 TI - Function of Integrin-Linked Kinase in Modulating the Stemness of IL-6-Abundant Breast Cancer Cells by Regulating gamma-Secretase-Mediated Notch1 Activation in Caveolae. AB - Interleukin-6 (IL-6) and Notch signaling are important regulators of breast cancer stem cells (CSCs), which drive the malignant phenotype through self renewal, differentiation, and development of therapeutic resistance. We investigated the role of integrin-linked kinase (ILK) in regulating IL-6-driven Notch1 activation and the ability to target breast CSCs through ILK inhibition. Ectopic expression/short hairpin RNA-mediated knockdown of ILK, pharmacological inhibition of ILK with the small molecule T315, Western blot analysis, immunofluorescence, and luciferase reporter assays were used to evaluate the regulation of IL-6-driven Notch1 activation by ILK in IL-6-producing triple negative breast cancer cell lines (MDA-MB-231, SUM-159) and in MCF-7 and MCF-7(IL 6) cells. The effects of ILK on gamma-secretase complex assembly and cellular localization were determined by immunofluorescence, Western blots of membrane fractions, and immunoprecipitation. In vivo effects of T315-induced ILK inhibition on CSCs in SUM-159 xenograft models were assessed by mammosphere assays, flow cytometry, and tumorigenicity assays. Results show that the genetic knockdown or pharmacological inhibition of ILK suppressed Notch1 activation and the abundance of the gamma-secretase components presenilin-1, nicastrin, and presenilin enhancer 2 at the posttranscriptional level via inhibition of caveolin 1-dependent membrane assembly of the gamma-secretase complex. Accordingly, knockdown of ILK inhibited breast CSC-like properties in vitro and the breast CSC subpopulation in vivo in xenograft tumor models. Based on these findings, we propose a novel function of ILK in regulating gamma-secretase-mediated Notch1 activation, which suggests the targeting of ILK as a therapeutic approach to suppress IL-6-induced breast CSCs. PMID- 26152359 TI - Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions. AB - Intrarenal interleukin-15 (IL-15) participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15) isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC) to peritumoral (ptumTEC), tumoral (RCC), and cancer stem cells (CSC/CD105(+)). RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor alpha (IL-15Ralpha) chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15) isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Ralpha). This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105(+), where it promotes survival. Indeed, through the AKT pathway, tmb-IL 15 protects CSC/CD105(+) from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa) displays a powerful anti apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, "apparently normal" ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral "preneoplastic" environment committed to favor tumor progression. PMID- 26152360 TI - Deleterious c-Cbl Exon Skipping Contributes to Human Glioma. AB - c-Cbl, a RING-type ubiquitin E3 ligase, downregulates various receptor tyrosine kinases (e.g., epidermal growth factor receptor (EGFR)), leading to inhibition of cell proliferation. Moreover, patients with myeloid neoplasm frequently harbor c Cbl mutations, implicating the role of c-Cbl as a tumor suppressor. Recently, we have shown that c-Cbl downregulates alphaPix-mediated cell migration and invasion, and the lack of c-Cbl in the rat C6 and human A172 glioma cells is responsible for their malignant behavior. Here, we showed that c-Cbl exon skipping occurs in the glioma cells and the brain tissues from glioblastoma patients lacking c-Cbl. This exon skipping resulted in generation of two types of c-Cbl isoforms: type I lacking exon-9 and type II lacking exon-9 and exon-10. However, the c-Cbl isoforms in the cells and tissues could not be detected as they were rapidly degraded by proteasome. Consequently, C6 and A172 cells showed sustained EGFR activation. However, no splice site mutation was found in the region from exon-7 to exon-11 of the c-Cbl gene in C6 cells and a glioblastoma tissue lacking c-Cbl. In addition, c-Cbl exon skipping could be induced when cells transfected with a c-Cbl mini-gene were grown to high density or under hypoxic stress. These results suggest that unknown alternations (e.g., mutation) of splicing machinery in C6 and A172 cells and the glioblastoma brain tissues are responsible for the deleterious exon skipping. Collectively, these findings indicate that the c-Cbl exon skipping contributes to human glioma and its malignant behavior. PMID- 26152361 TI - Bridging Links between Long Noncoding RNA HOTAIR and HPV Oncoprotein E7 in Cervical Cancer Pathogenesis. AB - Human Papillomavirus (HPV) type 16 oncoprotein E7 plays a major role in cervical carcinogenesis by interacting with and functionally inactivating various host regulatory molecules. Long noncoding RNA (lncRNA) HOTAIR is one such regulator that recruits chromatin remodelling complex PRC2, creating gene silencing H3K27 me3 marks. Hence, we hypothesized that HOTAIR could be a potential target of E7, in HPV16 related cervical cancers (CaCx). We identified significant linear trend of progressive HOTAIR down-regulation through HPV negative controls, HPV16 positive non-malignants and CaCx samples. Majority of CaCx cases portrayed HOTAIR down-regulation in comparison to HPV negative controls, with corresponding up regulation of HOTAIR target, HOXD10, and enrichment of cancer related pathways. However, a small subset had significantly higher HOTAIR expression, concomitant with high E7 expression and enrichment of metastatic pathways. Expression of HOTAIR and PRC2-complex members (EZH2 and SUZ12), showed significant positive correlation with E7 expression in CaCx cases and E7 transfected C33A cell line, suggestive of interplay between E7 and HOTAIR. Functional inactivation of HOTAIR by direct interaction with E7 could also be predicted by in silico analysis and confirmed by RNA-Immunoprecipitation. Our study depicts one of the causal mechanisms of cervical carcinogenesis by HPV16 E7, through modulation of HOTAIR expression and function. PMID- 26152362 TI - Safety and efficacy of concentrated topical epinephrine use in endoscopic endonasal surgery. AB - BACKGROUND: Effective topical decongestion is critical for the safe performance of endoscopic endonasal surgery (EES). Despite the vasoconstriction offered by topical concentrated (1:1000) epinephrine (CE), its use has not gained widespread acceptance because of concerns over systemic absorption and its effect on blood pressure and postoperative rebound epistaxis. The purpose of this study was to examine the physiological changes in blood pressure and rate of epistaxis with use of topical CE in a variety of endoscopic nasal procedures. METHODS: EES procedures using inhalational anesthesia and topical CE performed on 1140 consecutive patients (14 patients under 18 years) between 2011 and 2014 were evaluated retrospectively. Demographic data, intraoperative hemodynamic parameters, and postoperative epistaxis rates were recorded. RESULTS: The mean patient age was 45.8 years (range, 5-97 years). No intraoperative cardiovascular complications related to CE use were found. Four patients (0.35%) developed postoperative epistaxis requiring intervention. The mean estimated blood loss among patients undergoing bilateral sinus surgery, skull-base surgery, and orbital decompression was (mean +/- SD) 61.7 +/- 51.6 mL, 60.1 +/- 115 mL, and 67.9 +/- 42.2 mL, respectively. The maximum mean systolic blood pressure among these groups was 108.3 +/- 28.3 mmHg, 111.9 +/- 27.6 mmHg, and 95.1 +/- 31.7 mmHg, respectively. CONCLUSION: The use of topical CE is safe when performing endoscopic endonasal procedures. CE was not associated with any intraoperative complications. The profound intraoperative vasoconstriction does not confer a higher rate of postoperative rebound epistaxis. PMID- 26152363 TI - Medium-term CT evaluation of stent geometry, integrity, and valve function of the Edwards SAPIEN transcatheter heart valve in the pulmonary position. AB - OBJECTIVE: Distortion of transcatheter heart valve (THV) stent shape and morphology has been shown to impact on THV function. This study sought to evaluate the relationship between geometrical CT follow-up data and consequent valve function in patients undergoing transcatheter pulmonary valve replacement with the Edwards SAPIEN THV. METHODS: All patients were enrolled in the COMPASSION trial. Multidetector computed tomography (MDCT) was performed as part of the study protocol at 6 months and yearly thereafter following valve implantation. Prosthesis eccentricity indices, circularity ratios, and expansion ratios (ER) were calculated. Valve function and reintervention rates were correlated with MDCT findings. RESULTS: Twenty consecutive patients undergoing 58 CT scans were included. Maximum Doppler gradients across the right ventricular outflow tract (RVOT) were significantly reduced following valve implantation (P < 0.001). Geometrical indices and maximum RVOT gradients were compared between the reintervention group (n = 4) and the nonreintervention group (n = 16). Although there was no difference in eccentricity index between the groups, ER [6 months: 90 +/- 12% vs. 69 +/- 9%; P = 0.014; at 12 months: 89 +/- 14 vs. 69 +/- 10%; P = 0.018; at 24 months: 87 +/- 14% vs. 70 +/- 11%; P = 0.056] and valve area [6 months: 3.98 +/- 0.54 vs. 2.86 +/- 0.38 P = 0.005; at 12 months: 3.93 +/- 0.56 vs. 2.86 +/- 0.39 P = 0.006; 24 months: 3.78 +/- 0.50 vs. 2.90 +/- 0.45 P = 0.019] were lower in the reintervention group compared with the nonreintervention group at all time periods. CONCLUSION: Geometrical THV measurements as assessed by CT may predict the need for reintervention in patients undergoing transcatheter pulmonary valve replacement with the SAPIEN valve. Valve symmetry is maintained, however under-expansion and smaller valve area are strongly associated with the need for reintervention. PMID- 26152364 TI - Limitation of thiamine pyrophosphate supply to growing Escherichia coli switches metabolism to efficient D-lactate formation. AB - Efficient production of D-lactate by engineered Escherichia coli entails balancing cell growth and product synthesis. To develop a metabolic switch to implement a desirable transition from cell growth to product fermentation, a thiamine auxotroph B0013-080A was constructed in a highly efficient D-lactate producer E. coli strain B0013-070. This was achieved by inactivation of thiE, a gene encoding a thiamine phosphate synthase for biosynthesis of thiamine monophosphate. The resultant mutant B0013-080A failed to grow on the medium in the absence of thiamine yet growth was restored when exogenous thiamine was provided. A linear relationship between cell mass formation and amount of thiamine supplemented was mathematically determined in a shake flask experiment and confirmed in a 7-L bioreactor system. This calculation revealed that ~ 95-96 thiamine molecules per cell were required to satisfy cell growth. This relationship was employed to develop a novel fermentation process for D-lactate production by using thiamine as a limiting condition. A D-lactate productivity of 4.11 g . L(-1) . h(-1) from glycerol under microaerobic condition and 3.66 g . L( 1) . h(-1) from glucose under anaerobic condition was achieved which is 19.1% and 10.2% higher respectively than the parental strain. These results revealed a convenient and reliable method to control cell growth and improve D-lactate fermentation. This control strategy could be applied to other biotechnological processes that require optimal allocation of carbon between cell growth and product formation. PMID- 26152365 TI - Optimization of municipal solid waste collection and transportation routes. AB - Optimization of municipal solid waste (MSW) collection and transportation through source separation becomes one of the major concerns in the MSW management system design, due to the fact that the existing MSW management systems suffer by the high collection and transportation cost. Generally, in a city different waste sources scatter throughout the city in heterogeneous way that increase waste collection and transportation cost in the waste management system. Therefore, a shortest waste collection and transportation strategy can effectively reduce waste collection and transportation cost. In this paper, we propose an optimal MSW collection and transportation scheme that focus on the problem of minimizing the length of each waste collection and transportation route. We first formulize the MSW collection and transportation problem into a mixed integer program. Moreover, we propose a heuristic solution for the waste collection and transportation problem that can provide an optimal way for waste collection and transportation. Extensive simulations and real testbed results show that the proposed solution can significantly improve the MSW performance. Results show that the proposed scheme is able to reduce more than 30% of the total waste collection path length. PMID- 26152366 TI - Landfill mining: Case study of a successful metals recovery project. AB - Worldwide, the generation of municipal solid waste (MSW) is increasing and landfills continue to be the dominant method for managing solid waste. Because of inadequate diversion of reusable and recoverable materials, MSW landfills continue to receive significant quantities of recyclable materials, especially metals. The economic value of landfilled metals is significant, fostering interest worldwide in recovering the landfilled metals through mining. However, economically viable landfill mining for metals has been elusive due to multiple barriers including technological challenges and high costs of processing waste. The objective of this article is to present a case study of an economically successful landfill mining operation specifically to recover metals. The mining operation was at an ashfill, which serves a MSW waste-to-energy facility. Landfill mining operations began in November 2011. Between December 2011 and March 2015, 34,352 Mt of ferrous and non-ferrous metals were recovered and shipped for recycling, which consisted of metals >125 mm (5.2%), 50-125 mm (85.9%), <50mm (3.4%), zorba (4.6%), and mixed products (0.8%). The conservative estimated value of the recovered metal was $7.42 million. Mining also increased the landfill's airspace by 10,194 m(3) extending the life of the ashfill with an estimated economic value of $267,000. The estimated per-Mt cost for the extraction of metal was $158. This case study demonstrates that ashfills can be profitably mined for metals without financial support from government. Although there are comparatively few ashfills, the results and experience obtained from this case study can help foster further research into the potential recovery of metals from raw, landfilled MSW. PMID- 26152367 TI - Technical tip for difficult injection laryngoplasty: The use of a hypodermic needle as a retractor. PMID- 26152368 TI - Rate of disease progression: a prognostic biomarker in ALS. AB - OBJECTIVE: To assess the utility of rate of disease progression (DeltaFS) as a prognostic biomarker in amyotrophic laterals sclerosis (ALS). METHODS: A total of 203 patients with ALS were prospectively recruited over a 10-year period. At initial visit, the following variables were collected: demographic details, symptom duration, site of onset, phenotype, riluzole use and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. The DeltaFS score at initial visit was calculated by dividing the ALSFRS-R total score by symptom duration (months). The primary end point was survival. Kaplan-Meier survival curves were used to illustrate the distribution of survival from a specified point, while multiple Cox proportional hazards modelling with backward stepwise variable selection was used to identify the independent predictors of survival at initial visit. RESULTS: The DeltaFS score at initial visit was a significant predictor of survival in ALS (p<0.001), and remained significant when adjusted for age and site of onset (p<0.001). 3 prognostic subgroups emerged, with a DeltaFS score of <0.47 associated with a median survival of 2.4 years, which was significantly greater when compared with an initial DeltaFS score of between 0.47 and 1.11 (1.6 years, p<0.05) and a score >1.11 (0.7 years, p<0.001). Importantly, multiple Cox proportional hazards modelling identified DeltaFS as a highly significant independent predictor of survival in ALS (p<0.001) along with site of disease onset (p<0.01). CONCLUSIONS: Rate of disease progression appears to be a simple and sensitive clinical prognostic biomarker in ALS that could be potentially utilised in clinical practice and future therapeutic trials. PMID- 26152370 TI - Age-related aspects of human IgM(+) B cell heterogeneity. AB - The CD27(+) IgD(+) B cell population, known as IgM memory, reduces with age. It is thought that this population is responsible for pneumococcal polysaccharide T independent responses, and that the age-related reduction might be partially responsible for the increased susceptibility of older people to bacterial pathogens. There are other IgM(+) B cell populations that do not express IgD. We compared the different IgM populations using high-throughput sequencing of the immunoglobulin (Ig) gene repertoire and multidimensional cell phenotyping and found that the different populations of IgM cells, defined by CD27 and IgD expression, have repertoire differences. Some of these differences are likely indicative of different selection pressures in an immune response, although the older individuals were found to have a changed repertoire in naive B cells, which may contribute to some of the changes seen in memory cells. In addition, even within the CD27(+) IgD(+) IgM memory population there are multiple cell types. We show that the level of IgM expression varies substantially and hypothesize that this distinguishes between T-dependent and T-independent types of IgM memory cells. Significant age-related changes in the relative proportions of these populations may exacerbate the reduction in T-independent responders in old age. PMID- 26152369 TI - Pro-inflammatory TNFalpha and IL-1beta differentially regulate the inflammatory phenotype of brain microvascular endothelial cells. AB - BACKGROUND: The vasculature of the brain is composed of endothelial cells, pericytes and astrocytic processes. The endothelial cells are the critical interface between the blood and the CNS parenchyma and are a critical component of the blood-brain barrier (BBB). These cells are innately programmed to respond to a myriad of inflammatory cytokines or other danger signals. IL-1beta and TNFalpha are well recognised pro-inflammatory mediators, and here, we provide compelling evidence that they regulate the function and immune response profile of human cerebral microvascular endothelial cells (hCMVECs) differentially. METHODS: We used xCELLigence biosensor technology, which revealed global differences in the endothelial response between IL-1beta and TNFalpha. xCELLigence is a label-free impedance-based biosensor, which is ideal for acute or long-term comparison of drug effects on cell behaviour. In addition, flow cytometry and multiplex cytokine arrays were used to show differences in the inflammatory responses from the endothelial cells. RESULTS: Extensive cytokine secretion profiling and cell-surface immune phenotyping confirmed that the immune response of the hCMVEC to IL-1beta was different to that of TNFalpha. Interestingly, of the 38 cytokines, chemokines and growth factors measured by cytometric bead array, the endothelial cells secreted only 13. Of importance was the observation that the majority of these cytokines were differentially regulated by either IL-1beta or TNFalpha. Cell-surface expression of ICAM-1 and VCAM-1 were also differentially regulated by IL-1beta or TNFalpha, where TNFalpha induced a substantially higher level of expression of both key leukocyte-adhesion molecules. A range of other cell-surface cellular and junctional adhesion molecules were basally expressed by the hCMVEC but were unaffected by IL-1beta or TNFalpha. CONCLUSIONS: To our knowledge, this is the most comprehensive analysis of the immunological profile of brain endothelial cells and the first direct evidence that human brain endothelial cells are differentially regulated by these two key pro-inflammatory mediators. PMID- 26152371 TI - Epidemiology and outcomes of patients with invasive mould infections: a retrospective observational study from a single centre (2005-2009). AB - Invasive mould infection (IMI) is an important cause of morbidity and mortality in immunocompromised patients. However, Swedish epidemiology data are lacking. The aim of this study was to investigate the epidemiology and outcome of IMI. Cases of proven/probable IMI at Karolinska University Hospital, Stockholm, from 2005 to 2009, were included. A total of 100 patients with 104 episodes of IMI were enrolled. Identified isolates included 101 mould isolates. The majority of the isolates were Aspergillus spp. (74.3%), followed by Mucorales spp. (13.9%), Fusarium spp. (4.9%) and other mould spp. (6.9%). In 13% of the episodes, more than one mould caused the IMI. The lung was most often affected (88.5%). The most frequent underlying disease was haematological malignancies (70%). Following diagnosis, 83.7% initially received antifungal monotherapy, 9.6% received combination therapy and 6.7% no treatment. The overall 90-day and 1-year overall survival was 49% and 46% respectively. Survival at 90 days post diagnosis was 71.4% in the solid tumour cohort, 62.5% in patients with solid organ transplants, 43.5% in haematological malignancy (HMs) and 37% in those undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Overall survival was poor in the studied cohort, but is variable among different host categories, with particular opportunities for improvement in patients with underlying HMs and allogeneic HSCT. PMID- 26152375 TI - Unplanned 30-Day Readmissions in a General Internal Medicine Hospitalist Service at a Comprehensive Cancer Center. AB - PURPOSE: Hospital readmissions are considered by the Centers for Medicare and Medicaid as a metric for quality of health care delivery. Robust data on the readmission profile of patients with cancer are currently insufficient to determine whether this measure is applicable to cancer hospitals as well. To address this knowledge gap, we estimated the unplanned readmission rate and identified factors influencing unplanned readmissions in a hospitalist service at a comprehensive cancer center. METHODS: We retrospectively analyzed unplanned 30 day readmission of patients discharged from the General Internal Medicine Hospitalist Service at a comprehensive cancer center between April 1, 2012, and September 30, 2012. Multiple independent variables were studied using univariable and multivariable logistic regression models, with generalized estimating equations to identify risk factors associated with readmissions. RESULTS: We observed a readmission rate of 22.6% in our cohort. The median time to unplanned readmission was 10 days. Unplanned readmission was more likely in patients with metastatic cancer and those with three or more comorbidities. Patients discharged to hospice were less likely to be readmitted (all P values < .01). CONCLUSION: We observed a high unplanned readmission rate among our population of patients with cancer. The risk factors identified appear to be related to severity of illness and open up opportunities for improving coordination with primary care physicians, oncologists, and other specialists to manage comorbidities, or perhaps transition appropriate patients to palliative care. Our findings will be instrumental for developing targeted interventions to help reduce readmissions at our hospital. Our data also provide direction for appropriate application of readmission quality measures in cancer hospitals. PMID- 26152376 TI - Whose Risks and Benefits? PMID- 26152377 TI - Rationing Is Still Rationing. PMID- 26152378 TI - Can Voice Be Given If No One is Listening? PMID- 26152379 TI - The author replies. PMID- 26152380 TI - The author replies. PMID- 26152381 TI - Responsible Stewards of a Limited Resource. PMID- 26152382 TI - Candor about Adverse Events: Physicians versus the Data Bank. PMID- 26152383 TI - The Bitter Pill of Name-Brand Drugs. PMID- 26152384 TI - Punishing Health Care Providers for Treating Terrorists. PMID- 26152385 TI - Drifting Away from Informed Consent in the Era of Personalized Medicine. PMID- 26152386 TI - Training in Research Ethics and Standards for Community Health Workers and Promotores Engaged in Latino Health Research. PMID- 26152387 TI - Beyond Harms and Benefits: Rethinking Duties to Disclose Misattributed Parentage. PMID- 26152391 TI - Thinking All Wrong about How You Die. PMID- 26152388 TI - Fevered Decisions: Race, Ethics, and Clinical Vulnerability in the Malarial Treatment of Neurosyphilis, 1922-1953. AB - Physicians deliberately inoculated marginalized patients with malaria, using them as reservoirs to facilitate malarial fever therapy for syphilitic patients. The history presents ethical questions in an evolving historical context. PMID- 26152392 TI - Planning for Disaster. PMID- 26152393 TI - Cardiovascular disease genes come together. PMID- 26152394 TI - The double-barreled radial forearm osteocutaneous free flap. AB - OBJECTIVES/HYPOTHESIS: The radial forearm osteocutaneous free flap (RFOCFF) provides a thin pliable skin paddle with up to 11 cm of bone. A limitation of this flap is the thin bone that is obtained and the lack of suitability for dental implants. A minimum depth of 5 mm and height of 10 mm is required for a bony flap to accept osteointegrated implants. We propose that by double barreling the radial bone, it is possible to reconstruct osseous defects with bone of sufficient caliber to accept dental implants. STUDY DESIGN: Retrospective review of our experience with double-barreled RFOCFF. METHODS: We reviewed all free flaps performed from July 2000 to September 2014 and analyzed patients in whom a radial forearm osteocutaneous flap was used. We then reviewed those who had an osteotomy to form a double-barrel reconstruction. Descriptive data and outcomes were tabulated. RESULTS: A total of 458 osteocutaneous free flaps were performed; 75 were RFOCFF and 18 of these were double barreled. All 18 flaps survived. The reconstructed defect size was between 2.6 and 6.8 cm. One patient had dental implants placed at time of surgery that successfully osteointegrated. Postoperative computed tomography scans were available in nine patients and were used to calculate bone dimensions. Bone depth ranged from 7.91 to 13.22 mm, with a mean of 9.77 +/- 1.53 mm. Bone height ranged from 8.42 to 17.81 mm, with a mean of 13.82 +/- 3.2 mm. CONCLUSIONS: The double-barreled RFOCFF provides dependable long-lasting bone with adequate bone dimensions to support osteointegrated dental implants. LEVEL OF EVIDENCE: 4. PMID- 26152395 TI - Quantitative proteomics suggests decrease in the secretogranin-1 cerebrospinal fluid levels during the disease course of multiple sclerosis. AB - Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS with unknown cause. Proteins with different abundance in the cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients and neurological controls could give novel insight to the MS pathogenesis and be used to improve diagnosis, predict prognosis and disease course, and guide in therapy decisions. We combined iTRAQ labeling and Orbitrap mass spectrometry to discover proteins with different CSF abundance between six RRMS patients and 18 neurological disease controls. From 777 quantified proteins seven were selected as biomarker candidates, namely chitinase-3-like protein 1, secretogranin-1 (Sg1), cerebellin-1, neuroserpin, cell surface glycoprotein MUC18, testican-2 and glutamate receptor 4. An independent sample set of 13 early-MS patients, 13 RRMS patients and 13 neurological controls was used in a multiple reaction monitoring verification study. We found the intracellular calcium binding protein Sg1 to be increased in early-MS patients compared to RRMS and neurological controls. Sg1 should be included in further studies to elucidate its role in the early phases of MS pathogenesis and its potential as a biomarker for this disease. PMID- 26152396 TI - Scalable single-step microfluidic production of single-core double emulsions with ultra-thin shells. AB - We report a versatile and robust device for the continuous production of double emulsion drops with very thin shell thicknesses, of about 5% of the radius: for emulsions 50 MUm in radius the shells can be as thin as a few micrometers. Importantly, the viscosity of the oil shell can be varied from that of water up to 70 times that of water without compromising device operation. Furthermore, this device can be easily scaled-up as it is made through soft lithography; this may enable the production of industrial quantities of double emulsion drops with ultra-thin shells, which may serve as templates to form capsules with homogeneous shell thicknesses, useful beyond scientific applications. PMID- 26152397 TI - Obesity is an important health problem in survivors of pediatric acute lymphoblastic leukemia. PMID- 26152398 TI - Psychosocial job characteristics, wealth, and culture: differential effects on mental health in the UK and Thailand. AB - BACKGROUND: Most research on the influence of psychosocial job characteristics on health status has been conducted within affluent Western economies. This research addresses the same topic in a middle-income Southeast Asian country, enabling comparison with a Western benchmark. METHODS: We analysed and compared the Health Survey for England conducted in 2010 and the Thai Cohort Study data at 2005 baseline for workers aged 35-45 years. Multivariate logistic regression was used to assess relationships between psychosocial job characteristics and health, measured as Adjusted Odd Ratios (AOR), controlling for potential covariates in final analyses. RESULTS: In both UK and Thai working adults, psychological distress was associated with job insecurity (AOR 2.58 and 2.32, respectively), inadequate coping with job demands (AOR 2.57 and 2.42), and low support by employers (AOR 1.93 and 1.84). Job autonomy was associated with psychological distress in the UK samples (AOR 2.61) but no relationship was found among Thais after adjusting for covariates (AOR 0.99). Low job security, inability to cope with job demands, and low employer support were associated with psychological distress both among Thai and UK workers. CONCLUSIONS: Job autonomy was an important part of a healthy work environment in Western cultures, but not in Thailand. This finding could reflect cultural differences with Thais less troubled by individualistic expression at work. Our study also highlights the implications for relevant workplace laws and regulations to minimise the adverse job effects. These public health strategies would promote mental health and wellbeing in the population. PMID- 26152399 TI - Direct white-light and a dual-channel barcode module from Pr(III)-MOF crystals. AB - Direct white-light emission and further a dual-channel readable barcode module in both visible and NIR region was established by single-component homo-metallic Pr(iii)-MOF crystals for the first time. PMID- 26152401 TI - Kelch-like 3/Cullin 3 ubiquitin ligase complex and WNK signaling in salt sensitive hypertension and electrolyte disorder. AB - Pseudohypoaldosteronism type II (PHAII) is a hereditary disease characterized by salt-sensitive hypertension, hyperkalemia and thiazide sensitivity. Mutations in with-no-lysine kinase 1 (WNK1) and WNK4 genes are reported to cause PHAII. Rigorous studies have demonstrated that WNK kinases constitute a signaling cascade with oxidative stress-responsive gene 1 (OSR1), Ste20-related proline alanine-rich kinase (SPAK) and the solute carrier family 12a (SLC12a) transporter, including thiazide-sensitive NaCl cotransporter. The WNK-OSR1/SPAK SLC12a signaling cascade is present in the kidneys and vascular smooth muscle cells (VSMCs) and regulates salt sensitivity physiologically, i.e. urinary sodium excretion and arterial tone by various hormonal and dietary factors. However, although it was clear that the abnormal activation of this signaling cascade is the molecular basis of PHAII, the molecular mechanisms responsible for the physiological regulation of WNK signaling and the effect of WNK4 mutations on PHAII pathogenesis are poorly understood. Two additional genes responsible for PHAII, Kelch-like 3 (KLHL3) and Cullin 3 (CUL3), were identified in 2012. WNK1 and WNK4 have been shown to be substrates of KLHL3-CUL3 E3 ubiquitin ligase both in vitro and in vivo In PHAII, the loss of interaction between KLHL3 and WNK4 induces increased levels of WNK kinases due to impaired ubiquitination. These results indicate that WNK signaling is physiologically regulated by KLHL3/CUL3 mediated ubiquitination. Here, we review recent studies investigating the pathophysiological roles of the WNK signaling cascade in the kidneys and VSMCs and recently discovered mechanisms underlying the regulation of WNK signaling by KLHL3 and CUL3. PMID- 26152400 TI - Predicting Health Resilience in Pediatric Type 1 Diabetes: A Test of the Resilience Model Framework. AB - OBJECTIVES: This research examined whether individual and family-level factors during the transition from late childhood to early adolescence protected individuals from an increased risk of poor glycemic control across time, which is a predictor of future diabetes-related complications (i.e., health resilience). METHODS: This longitudinal, multisite study included 239 patients with type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c. Individual and family-level factors included: demographic variables, youth behavioral regulation, adherence (frequency of blood glucose monitoring), diabetes self-management, level of parental support for diabetes autonomy, level of youth mastery and responsibility for diabetes management, and diabetes-related family conflict. RESULTS: Longitudinal mixed-effects logistic regression indicated that testing blood glucose more frequently, better self-management, and less diabetes-related family conflict were indicators of health resilience. CONCLUSIONS: Multiple individual and family-level factors predicted risk for future health complications. Future research should develop interventions targeting specific individual and family-level factors to sustain glycemic control within recommended targets, which reduces the risk of developing future health complications during the transition to adolescence and adulthood. PMID- 26152402 TI - Effects of blood pressure on renal and cardiovascular outcomes in Asian patients with type 2 diabetes and overt nephropathy: a post hoc analysis (ORIENT-blood pressure). AB - BACKGROUND: Blood pressure (BP) control may have different effects on cardiovascular (CV) and renal outcomes in diabetes. We examined the impact of systolic BP (SBP) on renal and CV outcomes in a post hoc analysis in the Olmesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial. METHODS: We stratified mean follow-up SBP into three categories (<=130, 131-140 and >140 mmHg) and used a Cox regression model to estimate the hazard ratio (HR, 95% confidence interval) for the outcomes. The composite renal outcome was doubling of serum creatinine, end-stage renal disease and all-cause death. The composite CV outcome included CV death, nonfatal stroke, nonfatal myocardial infarction, hospitalization for unstable angina or heart failure, revascularization and lower extremity amputation. We also compared the slope of estimated glomerular filtration rate (eGFR) in all three groups. RESULTS: After a mean follow-up period of 3.2 years, the follow-up SBP was linearly associated with risk of renal outcomes in all 566 patients. In patients with heavy proteinuria (>=1 g/gCr), a follow-up SBP > 130 mmHg was associated with an HR of 2.33 (1.62-3.36) for renal outcomes with referent to SBP <= 130 mmHg. In patients without history of CV disease, a follow-up SBP > 140 mmHg was associated with an HR of 2.04 (1.23-3.40) for CV outcomes with referent to SBP < 140 mmHg. The median (interquartile range) slopes of eGFR were -3.27 (-6.90, -1.63), -4.53 ( 8.08, -2.29) and -7.13 (-10.90, -3.99) dL/mg/year in patients with SBP <= 130, 131-140 and > 140 mmHg, respectively (P = 0.008 between <=130 and 131-140, P < 0.001 between <= 130 and > 140 mmHg). CONCLUSION: In Asian type 2 diabetic patients with chronic kidney disease and heavy proteinuria, reduction of SBP <= 130 mmHg was associated with greater renoprotection than cardioprotection. However, our results emphasize the need to individualize BP targets in type 2 diabetes. PMID- 26152404 TI - Evaluation and management of diabetic and non-diabetic hypoglycemia in end-stage renal disease. AB - Patients with end-stage renal disease (ESRD) regardless of diabetes status are at increased risk of hypoglycemia with a resultant array of adverse clinical outcomes. Therefore, hypoglycemia should be thoroughly evaluated in ESRD patients. In diabetic dialysis patients, hypoglycemic agents and nutritional alterations can trigger hypoglycemia in the background of diminished gluconeogenesis, reduced insulin clearance by the kidney and improved insulin sensitivity following initiation of renal replacement therapy. Detailed evaluation of antidiabetic regimen and nutritional patterns, patient education on self-monitoring of blood glucose and/or referral to a diabetes specialist may reduce risk of subsequent hypoglycemia. In certain situations, it is important to recognize the possibility of non-diabetic causes of hypoglycemia in patients with diabetes and to avoid treating pseudo-hyperglycemia caused by glucose- non specific glucometers in patients utilizing icodextrin-based solutions for peritoneal dialysis. Adrenal insufficiency, certain medications, malnutrition and/or infection are among the most common causes of hypoglycemia in non-diabetic ESRD patients, and they should be suspected after exclusion of inadvertent use of hypoglycemic agents. The goal of this review article is to summarize approaches and recommendations for the work up and treatment of hypoglycemia in ESRD. PMID- 26152403 TI - APOL1 nephropathy risk variants are associated with altered high-density lipoprotein profiles in African Americans. AB - BACKGROUND: Two independent coding variants in the apolipoprotein L1 gene (APOL1), G1 and G2, strongly associate with nephropathy in African Americans; associations with cardiovascular disease are more controversial. Although APOL1 binds plasma high-density lipoproteins (HDLs), data on APOL1 risk variant associations with HDL subfractions are sparse. METHODS: Two APOL1 G1 single nucleotide polymorphisms and the G2 insertion/deletion polymorphism were genotyped in 2010 Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study participants with nuclear magnetic resonance spectroscopy-based lipoprotein subfraction measurements. Linear regression was used to model associations between numbers of APOL1 G1/G2 risk variants and HDL subfractions, adjusting for demographic, clinical and ancestral covariates. RESULTS: Female sex and higher percentage of African ancestry were positively associated with the number of APOL1 G1/G2 risk alleles. In the unadjusted analysis, mean (standard error) small HDL concentrations (MUmol/L) for participants with zero, one and two G1/G2 risk alleles were 19.0 (0.2), 19.7 (0.2) and 19.9 (0.4), respectively (P = 0.02). Adjustment for age, sex, diabetes and African ancestry did not change the results but strengthened the statistical significance (P = 0.004). No significant differences in large or medium HDL, very low-density lipoprotein or low-density lipoprotein particle concentrations were observed by APOL1 genotype. CONCLUSIONS: Greater numbers of APOL1 G1/G2 risk alleles were associated with higher small HDL particle concentrations in African Americans. These results may suggest novel areas of investigation to uncover reasons for the association between APOL1 risk variants with adverse outcomes in African Americans. PMID- 26152405 TI - Association between urinary lead and bone health in a general population from Taiwan. AB - Lead accumulates in adult bones for many decades; previous studies have shown lead's detrimental effects on osteoblast and osteoclast activity in association with bone remodeling. Osteoporosis is a disease of the bones resulting in low bone mass that induces fragile bones and hence susceptibility of fracture. We estimated the association between urinary lead (U-Pb) levels and bone health in adults participating in the third Nutrition and Health Survey in Taiwan (NAHSIT) from 2005 to 2008. A total of 398 participants were divided into normal (T-score> 1), osteopenic (T-score between -1 and -2.5), or osteoporotic (T-score<-2.5) groups according to the results of bone mineral density (BMD) measurements. Heavy metals were measured in urine specimens using inductively coupled plasma-mass spectrometry. In the multivariable logistic regression analysis, age (OR=1.08; 95% CI=1.05-1.10), former smokers (OR=2.95; 95% CI=1.22-7.11) and higher U-Pb levels than upper tertile (OR=2.30; 95% CI=1.19-4.48) were associated with osteopenia/osteoporosis. Furthermore, age (OR=1.06; 95% CI=1.02-1.10) and higher U-Pb levels (OR=2.81; 95% CI=1.13-6.97) were significantly associated with osteopenia and osteoporosis in women. These results suggest that adults, particularly in women, with higher U-Pb levels may have increased odds of osteopenia and osteoporosis. PMID- 26152406 TI - Importance of Air Particle Counts in Hospital Infection Control: Insights From a Cancer Center in Eastern India. PMID- 26152407 TI - Susceptibility of Adult Cat Fleas (Siphonaptera: Pulicidae) to Insecticides and Status of Insecticide Resistance Mutations at the Rdl and Knockdown Resistance Loci. AB - The susceptibility of 12 field-collected isolates and 4 laboratory strains of cat fleas, Ctenocephalides felis was determined by topical application of some of the insecticides used as on-animal therapies to control them. In the tested field collected flea isolates the LD50 values for fipronil and imidacloprid ranged from 0.09 to 0.35 ng/flea and 0.02 to 0.19 ng/flea, respectively, and were consistent with baseline figures published previously. The extent of variation in response to four pyrethroid insecticides differed between compounds with the LD50 values for deltamethrin ranging from 2.3 to 28.2 ng/flea, etofenprox ranging from 26.7 to 86.7 ng/flea, permethrin ranging from 17.5 to 85.6 ng/flea, and d-phenothrin ranging from 14.5 to 130 ng/flea. A comparison with earlier data for permethrin and deltamethrin implied a level of pyrethroid resistance in all isolates and strains. LD50 values for tetrachlorvinphos ranged from 20.0 to 420.0 ng/flea. The rdl mutation (conferring target-site resistance to cyclodiene insecticides) was present in most field-collected and laboratory strains, but had no discernible effect on responses to fipronil, which acts on the same receptor protein as cyclodienes. The kdr and skdr mutations conferring target-site resistance to pyrethroids but segregated in opposition to one another, precluding the formation of genotypes homozygous for both mutations. PMID- 26152409 TI - Chemical Compatibility and Safety of Imidacloprid/Flumethrin Collar (Seresto(r)) Concomitantly Used with Imidacloprid/Moxidectin (Advocate(r), Advantage(r) Multi) and Emodepside/Praziquantel (Profender(r)) Spot-on Formulations. AB - Safety of concomitant use of veterinary products is of clinical interest. A series of studies was performed to evaluate the chemical compatibility and short term dermal and systemic safety of an imidacloprid/flumethrin collar (Seresto((r))/ Foresto((r)), Bayer) used concomitantly with spot-on or tablet formulations.Chemical compatibility was evaluated in-vitro (study reference A) on collar pieces, followed by two small, non-controlled clinical studies (study reference B) in both, cats and dogs. The studies showed, that certain solvents affected the collar in-vitro, but not in their marketed formulations.Dermal and systemic safety of different spot-on or tablet formulations was first evaluated in a small, non-controlled clinical study (study reference C) in cats and dogs, via clinical observations only, followed by controlled clinical safety studies of concomitant use with imidacloprid/ moxidectin (Advocate((r))/ Advantage((r)) Multi, Bayer) in dogs and cats (study reference D) and emodepside/ praziquantel (Profender((r)), Bayer) in cats (study reference E), assessing safety aspects by clinical observations and statistical analyses of hematology and clinical chemistry parameters compared to baseline values and between treated and control groups.Dermal safety findings over all clinical studies (study references B to E) matched those already described for the respective products and included transient cosmetic changes (oily hair and crystal formation) at the site of spot on application and broken hair, transient alopecia and skin alterations at the site of collar application. There were no indications of these findings aggravating under the conditions of concurrent use. There were no systemic safety findings of clinical significance in any of the clinical safety studies (study reference C to E). Assessment of blood parameters revealed some deviations from baseline levels and from the reference range in dogs as well as in cats, but no clinical relevance could be deduced. Hematology and clinical chemistry results confirmed the safety of the concomitant treatment. It is concluded that Seresto((r)) is chemically compatible with solvents used in major spot-on formulations on the market and is dermally and systemically safe for adult dogs and cats when used concomitantly with Advocate((r)) and Profender((r)) spot-on formulations. PMID- 26152408 TI - Tick-borne Diseases (Borreliosis, Anaplasmosis, Babesiosis) in German and Austrian Dogs: Status quo and Review of Distribution, Transmission, Clinical Findings, Diagnostics and Prophylaxis. AB - Tick-borne diseases (TBD) in dogs have gained in significance in German and Austrian veterinary practices. The widespread European tick species Ixodes ricinus represents an important vector for spirochaetes of the Borrelia burgdorferi sensu lato group and Rickettsiales such as Anaplasma phagocytophilum. The meadow or ornate dog tick (Dermacentor reticulatus) is an important vector for Babesia canis, as is the brown dog tick (Rhipicephalus sanguineus) for Babesia vogeli in the Mediterranean region. The present work covers pathogen transmission by tick vectors, including the mechanisms and the minimum intervals required, in conjunction with possible non-vector-borne transmission routes. It also addresses the incubation periods, pathogenicity and clinical findings associated with each pathogen and genospecies and presents case examples. Current data on prevalence, annual fluctuations and distribution in various pre-selected dog populations (symptomatic versus asymptomatic) in both countries are depicted in maps. Reasons for changes in prevalence (especially of Borrelia) are discussed. Criteria and algorithms for clinical diagnosis and monitoring in dogs, including case history, direct detection (blood smears, molecular detection by species-specific PCR and sequencing) and indirect methods (whole-cell and peptide based antibody tests), are presented, together with laboratory abnormalities (haematology, clinical chemistry, urine). The role of anti-C6 antibody concentration (ACAC) and its correlation with proteinuria and Lyme nephritis are assessed on the basis of new data. Consideration is also given to the importance of blood smears, PCR and serology in the case of anaplasmosis and babesiosis, and the diagnostic value of combining these methods. The relevance of molecular differentiation of Anaplasma species (A. phagocytophilum versus A. platys) and Babesia spp. (large versus small forms) in cases of serological cross-reaction is emphasized. A summary is given of methods for prophylaxis using acaricide products (collars, spot-on solutions and oral treatments in both countries), vaccination (Borrelia and Babesia vaccines) and imidocarb-based chemoprophylaxis for large Babesia. PMID- 26152410 TI - Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto(r)) and an Oral Afoxolaner Chewable (NexGard(r)) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial. AB - This randomised controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto((r)), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours postinfestation on dogs when compared to oral afoxolaner (NexGard((r)), Merial). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w) / flumethrin 4.5 % (w/w) collar, 2) afoxolaner chewable (dosage 3.1 - 6.2 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, and 28; live (attached and non-attached) and dead attached ticks were counted 6 and 12 hours later. Efficacy against live D. variabilis at 6 hours for Group 1 was 95 - 100 % and for Group 2 was 38 - 48 %; efficacy at 12 hours for Group 1 was 97 - 100 % and for Group 2 was 27 - 59 %. Efficacy against A. americanum at 6 hours for Group 1 was 94 - 100 % and for Group 2 was < 0 - 38 %; efficacy at 12 hours for Group 1 was 98 - 100 % and for Group 2 was 1 - 40 %. Live and total (total live and dead attached) tick counts in Group 1 against both tick species were significantly lower (p <= 0.05) than Group 2 and 3 at all time points. The number of live or total ticks on Group 2 dogs was never significantly lower when compared to the respective number of ticks on Group 3 (controls). This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post infestation and was more efficacious than afoxolaner on all challenge days. PMID- 26152411 TI - Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto(r)) and an Oral Fluralaner Chewable Tablet (Bravecto(r)) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial. AB - This controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto((r)), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours post-infestation on dogs when compared to oral fluralaner (Bravecto((r)), Merck). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w)/flumethrin 4.5 % (w/w) collar, 2) fluralaner (dosage 25.1 - 49.4 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, 28, 42, and 56 followed by 50 D. variabilis on days 70 and 84. Live and dead attached ticks were counted 6 and 12 hours later. Efficacy against both species at 6 and 12 hours for Group 1 was 94 - 100 %. Efficacy for Group 2 against both species at 6 hours was 4 - 69 %; efficacy at 12 hours was 8 - 100 %. Live (attached and non-attached) tick counts at 6 hours in Group 1 were significantly lower (p <= 0.05) than counts in Group 2 and 3 on all days. At 12 hours, live counts were significantly lower (p <= 0.05) in Group 1 than Group 2 for D. variabilis from days 56 - 84 and for A. americanum from days 28 - 56. There were significantly fewer (p <= 0.05) total ticks (total live and dead attached) on dogs in Group 1 compared to Group 2 and 3 at all time points. This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than fluralaner as early as 6 hours post-infestation on all challenge days. PMID- 26152412 TI - Comparative Speed of Kill, Repellent (anti-feeding) and Acaricidal Efficacy of an Imidacloprid/Flumethrin Collar (Seresto(r)) and a Fipronil/(S) Methoprene/Eprinomectin/Praziquantel Spot-on (Broadline(r)) against Ixodes ricinus (Linne, 1758) on Cats. AB - Speed of kill, repellent (anti-feeding) and acaricidal efficacy of an imidacloprid 10 % (w/w) /flumethrin 4.5 % (w/w) collar (Seresto((r)), Bayer) and a spot-on formulation of fipronil 8.3 % (w/v) /(S)-methoprene 10 % (w/v) /eprinomectin 0.4 % (w/v) /praziquantel 8.3 % (w/v) (Broadline((r)), Merial) against artificiallyinduced infestations with Ixodes ricinus on cats, were assessed in a parallel group design, randomised, controlled study. Twenty-four cats were included and randomly allocated to treatment groups or a non-treated control group. Starting on Day (D) 7 after treatment until D28, cats were each infested with 50 I. ricinus at weekly intervals. Ticks were counted in situ on the cats at 6, 12 and 24 h and upon removal 48 h after each infestation. Based on arithmetic means, Seresto((r)) proved to be 100 % effective against adult I. ricinus at all assessment times (6, 12, 24 and 48 h after infestation) throughout the month-long study. Broadline((r)) was 0 % to 16.7 % effective at 6 h, 26.8 % to 50.0 % effective at 12 h, while at 24 h after infestation efficacy peaked at 81.5 % on D15 declining to 31.5 % on D29. Based on the 48 h tick counts, the efficacy of Broadline((r)) peaked at 100 % on D16 after treatment and decreased to 83.2 % by D30. The Seresto((r)) collar provided significantly faster speed of kill and better persistent acaricidal effectiveness against Ixodes ricinus on cats compared to Broadline((r)) spot-on. The additional repellent (anti-feeding) effect of Seresto((r)) prevents parasites from taking a blood meal and thereby reduces the risk of vector-borne disease pathogen transmission. PMID- 26152413 TI - Current Surveys of the Seroprevalence of Borrelia burgdorferi, Ehrlichia canis, Anaplasma phagocytophilum, Leishmania infantum, Babesia canis, Angiostrongylus vasorum and Dirofilaria immitis in Dogs in Bulgaria. AB - Canine vector-borne diseases (CVBDs) have increasingly become a focus of interest in recent years. Some of the CVBDs are zoonotic and may therefore also represent a risk for the human population. Different factors are in discussion to explain the expansion of vectors and pathogens into formerly unaffected areas. Knowledge of the prevalence and distribution of CVBDs in Bulgaria is scant overall and most data rely on single case descriptions. The aim of the present study was to determine the seroprevalence of important CVBDs in 167 dogs from central-southern Bulgaria (Stara Zagora), with special emphasis on hitherto uninvestigated babesiosis and angiostrongylosis, on poorly investigated Lyme borreliosis and canine granulocytic anaplasmosis, and on the potentially zoonotic dirofilariosis and leishmaniosis. Relatively high prevalence rates were documented for anti Babesia canis antibodies, Dirofilaria immitis antigen (16.2 %; 27/167 each), anti Ehrlichia canis (21 %; 35/167) and anti-Anaplasma phagocytophilum antibodies (30.5 - 46.1 %; 51 - 77/167), while Borrelia burgdorferi seroprevalence was low (2.4 %; 4/167). All samples were negative for Leishmania infantum antibodies and Angiostrongylus vasorum antigen and antibodies. In total, 64.7 % (108/167) of the samples indicated infection or exposure to at least one agent and a high proportion of dual infections (39.8 %; 43/108) was demonstrated. Multiple infections with up to four different organisms were also detected. Our data underline the importance of CVBDs and especially of co-infections which could influence the clinical outcome in dogs. PMID- 26152414 TI - Evaluation of the Adulticidal Efficacy of Imidacloprid 10 %/Moxidectin 2.5 % (w/v) Spot-on (Advocate(r), Advantage(r) Multi) against Dirofilaria repens in Experimentally Infected Dogs. AB - This study aimed to evaluate the efficacy of imidacloprid 10 %/moxidectin 2.5 % (w/v) spot-on (Advocate(r)/Advantage(r) Multi, Bayer) against adult Dirofilaria repens in a blinded, placebo-controlled randomised laboratory study. Twenty-four Beagle dogs were experimentally infected with approximately 75 infective D. repens larvae each on study day (SD) 0. Treatment was initiated on SD 228 after patency had been confirmed in 21 dogs, using a modified Knott Test. Eleven dogs received monthly treatments with imidacloprid/moxidectin at the minimum therapeutic dose (10 mg/kg imidacloprid and 2.5 mg/kg moxidectin) for six consecutive months and 12 control dogs were treated with a placebo formulation. Approximately one month after the last treatment, all dogs were euthanised and necropsied for the detection of D. repens worms. Eleven control dogs harboured live adult D. repens (range 2-11, geometric mean 5.44). Eight of 11 imidacloprid/moxidectin-treated dogs were free of live worms. The live worm count was reduced by 96.2 % (range 0-1, geometric mean 0.21). The majority of dead worms were encapsulated and degenerated. After the first treatment, Knott Tests were negative in all imidacloprid/moxidectin-treated dogs and this status was maintained in 10 dogs until study end. One dog showed a low microfilariae count (1 and 4/mL) on four occasions but was also negative before necropsy. The treatment was well tolerated by all study animals. It is concluded that six consecutive monthly treatments with imidacloprid/moxidectin spot-on are effective and safe against adult D. repens and provide an option for preventing the further spread of this zoonotic parasite. PMID- 26152415 TI - Combined Serological Detection of Circulating Angiostrongylus vasorum Antigen and Parasite-specific Antibodies in Dogs from Hungary. AB - The occurrence of the nematode Angiostrongylus vasorum, also known as the French heartworm, is increasingly being reported from various European countries. The adults of this parasite species live in the pulmonary arteries and right cardiac ventricle of wild canids and domestic dogs. Larval stages and eggs in the lungs induce inflammatory verminous pneumonia, causing severe respiratory disease in dogs. Furthermore, haematological and neurological signs and even death may occur. In Hungary, A. vasorum has been identified in red foxes, golden jackals and in two dogs and some slugs. In this first large-scale survey, 1247 sera from pet dogs were collected and tested by an ELISA for the detection of circulating antigen of A. vasorum and by a separate ELISA to detect specific antibodies against the parasite. A total of 1.36% (n = 17, 95 % confidence intervals, CI: 0.80 - 2.17 %) of the animals were positive in both ELISAs, while 1.76 % (n = 22, CI: 1.11 - 2.66 %) of the tested dogs were antigen-positive only and 2.73 % (n = 34, CI: 1.90 - 3.79 %) were positive for specific antibodies only. Regions with antigen- and antibody-positive animals overlapped and were distributed over nearly the whole sampled areas of the country. A considerable number of cases was observed in Budapest and also in the southern part of the country bordering Croatia, while in the most eastern part bordering Ukraine no positive samples were detected. These results confirm the endemic occurrence of A. vasorum in dogs originating from different parts of Hungary and the significant advantages of A. vasorum serology in epidemiological studies. PMID- 26152416 TI - Efficacy of Emodepside/Praziquantel Spot-on (Profender(r)) against adult Aelurostrongylus abstrusus Nematodes in Experimentally Infected Cats. AB - The adulticidal efficacy of a topical combination of emodepside 2.1 % (w/v) plus praziquantel 8.6 % (w/v) (Profender(r) spot-on for cats, Bayer) against adult Aelurostrongylus abstrusus nematodes was evaluated in two randomised, placebo controlled laboratory efficacy studies. Each study involved 16 cats experimentally inoculated with L3 (800 and 600 each in studies no. 1 and 2, respectively) and randomised into two study groups of 8 cats each after onset of patency. While cats in the treatment group in study no. 1 received a single spot on application at the minimum therapeutic dose (3 mg/kg emodepside and 12 mg/kg praziquantel), cats in study no. 2 were treated twice with an interval of 14 days. The faecal output of first stage larvae was monitored throughout the study. Necropsy was conducted 4 or 5 weeks after the (first) treatment and the worm counts were used for efficacy calculations. The control groups showed a geometric mean of the total worm count (live and dead worms) of 28.8 (study no. 1) and 17.6 (study no. 2), respectively. All control animals were infected. While the single treatment in study no. 1 resulted in a reduction of the total worm burden by 73.0 % (p = 0.0070), the treatment protocol in study no. 2 was 99.2 % effective (p = 0.0035). Based on live worm counts, the efficacy in study no. 2 was 100 % (p = 0.0030). It is concluded that two applications of Profender(r) spot-on given two weeks apart represent a safe and highly efficacious treatment regime against feline aelurostrongylosis. PMID- 26152417 TI - Laboratory Evaluation of the Efficacy of 10 % Imidacloprid + 2.5 % Moxidectin Topical Solution (Advantage(r) Multi, Advocate(r)) for the Treatment of Dirofilaria immitis Circulating Microfilariae in Dogs. AB - This study examined the efficacy of 10 % imidacloprid + 2.5 % moxidectin topical solution (Advantage (r) Multi, Advocate(r), Bayer) for the treatment of circulating microfilariae from dogs naturally infected with Dirofilaria immitis. The study included two groups of 11 dogs each that consisted of two replicates. Replicate 1 contained 12 dogs (6 treated and 6 controls) and replicate 2 contained 10 dogs (5 treated and 5 controls). Six of the 10 dogs in replicate 2 were the controls from replicate 1. All dogs entering the study completed a physical examination including chest radiographs, blood collections for examination of Dirofilaria immitis circulating microfilariae, serum chemistry, complete blood counts and urinalysis. To qualify for the study each dog was required to have a geometric mean >= 300 microfilariae per ml of blood from 3 consecutive samples collected during the 8 day acclimation period and a heartworm disease classification of 1 or 2. Dogs were treated on study days 0 and 28. Post treatment microfilarial counts were performed on study days 1, 2, 3, 7, 14, 21, 28, 29, 35, and 42. Percent microfilarial reduction was determined by comparing the geometric mean number of circulating microfilaria remaining in treated dogs with those remaining in the control dogs post-treatment. Seven days after the first treatment, the geometric mean microfilarial counts in treated dogs were reduced by > 99 % compared to the control dogs. Reduction remained at > 99 % through the end of the study at 42 days after the first treatment (14 days after the second treatment). The results of this study demonstrated that Advantage(r) Multi for dogs is efficacious for treatment of circulating D. immitis microfilariae in naturally infected heartworm-positive dogs with no treatment related adverse events observed. PMID- 26152418 TI - Prevention of Lactogenic Toxocara cati Infections in Kittens by Application of an Emodepside/Praziquantel Spot-on (Profender(r)) to the Pregnant Queen. AB - This study aimed to evaluate the efficacy of an emodepside 2.1 % (w/v)/praziquantel 8.6 % (w/v) topical solution (Profender(r) spot-on for cats) in the prevention of lactogenic Toxocara cati infections. A controlled test was performed with two groups of 8 cats with confirmed pregnancy. All cats were infected with daily doses of 2000 T. cati eggs for 10 consecutive days starting 50 days post conception to produce an acute infection. Treatment was performed 60 days post conception. Queens in the treatment group received the emodepside/praziquantel solution at the minimum therapeutic dose (3 mg/kg emodepside and 12 mg/kg praziquantel), while the control group was treated with a placebo spot-on. Efficacy was evaluated 56 days post partum by necropsy of one randomly selected kitten of each litter and comparison of the worm burdens between the study groups. Additionally the necropsy results were supported by quantification of worms expelled with the faeces after deworming of the remaining kittens and all queens. The treatment in late pregnancy resulted in an efficacy of 98.7 % (p < 0.0001). All necropsied control kittens were infected (geometric mean 30.6). Seven of 8 kittens from treated mothers were free of T. cati (geometric mean 0.4). Worm counts after deworming reflected the results obtained at necropsy. No side effects of the treatment were observed. It is concluded that treatment with an emodepside/praziquantel spot-on solution during late pregnancy effectively prevents lactogenic transmission of T. cati to the offspring. The study design facilitated the generation of reliable data, while at the same time a minimum number of animals was sacrificed. PMID- 26152419 TI - Detection of Angiostrongylus vasorum in Red Foxes (Vulpes vulpes) from Brandenburg, Germany. AB - Angiostrongylus (A.) vasorum is a nematode that causes angiostrongylosis in domestic and wild canids. Red foxes (Vulpes vulpes) and raccoon dogs (Nyctereutes procyonoides) are suspected of providing a wildlife reservoir for A. vasorum infections in pet dogs. To obtain data on the occurrence of A. vasorum in wildlife, red fox and raccoon dog carcasses (hunted or found dead) were collected from January to September 2009 in the Federal State of Brandenburg, Germany. Lung tissue samples were subjected to DNA extraction and examined for the presence of A. vasorum DNA by means of real-time PCR. A. vasorum DNA was detected in 11 out of 122 (9.0 %) lungs of red foxes and in none of the lung samples of raccoon dogs. These data suggest that red foxes are a reservoir of A. vasorum infections for pet dogs in this area. PMID- 26152420 TI - Field Evaluation of the Effectiveness of an Oral Toltrazuril and Iron Combination (Baycox(r) Iron) in Maintaining Weaning Weight by Preventing Coccidiosis and Anaemia in Neonatal Piglets. AB - Effectiveness of an oral combination of toltrazuril and iron dextran (Baycox((r)) Iron) to maintain weaning weight by preventing coccidiosis caused by Isospora suis and iron-deficiency anaemia in neonatal piglets was investigated on three commercial pig farms with a history of coccidiosis: two in Mexico and one in Brazil. On day (SD) 2 of life, piglets were randomised within litter by bodyweight to treatment or control group. On SD 3 piglets allocated to the control group (CG) each received 1 mL Baycox((r)), containing 50 mg/mL toltrazuril orally and commercially available iron (200 mg/piglet) by intramuscular injection. Piglets allocated to the treatment group (TG) each received 1 mL toltrazuril and iron combination orally (Baycox((r)) Iron) containing 50 mg/mL toltrazuril and 228 mg iron as iron dextran. All piglets had access to creep feed. 6493 piglets completed the study. Bodyweight at weaning on SD 21 of piglets treated with the oral toltrazuril and iron combination was confirmed to be non-inferior to the control treatment with <1 % difference between group mean body weights. Faecal samples from at least 10 % of litters on SD 14 demonstrated control of coccidiosis. Haemoglobin levels on SD 21 were lower in the oral toltrazuril and iron combination treated piglets compared to control levels but above minimum haemoglobin levels to maintain health. There was no difference in mortality between the two groups. This large scale field evaluation clearly demonstrated the effectiveness of a combination of oral toltrazuril and iron (Baycox((r)) Iron) in maintaining body weight at weaning compared to conventional treatment. The combination was effective in preventing coccidiosis and anaemia and thus provides a valuable alternative that reduces stressful events in neonatal piglets. There were no product related adverse events. PMID- 26152422 TI - 2015 WAAVP Liverpool 16 - 20 August. PMID- 26152421 TI - Significance of Timing on Effect of Metaphylactic Toltrazuril Treatment against Eimeriosis in Calves. AB - In this multicentric, randomised, blinded and placebo-controlled field study, the effect of treatment with toltrazuril (Baycox((r)) Bovis, Bayer) on oocyst excretion, diarrhoea score and weight gain was studied in Danish dairy herds with confirmed history of eimeriosis (coccidiosis) and prevalence of Eimeria bovis and Eimeria zuernii. Three commercial herds and a total of 71 calves, aged 48 - 135 days, were included. Treatment with a single oral dose of toltrazuril (15 mg/kg) was given after relocation to common pens and one week before expected outbreak of eimeriosis. The effect of treatment was followed by weekly faecal sampling and weighing initially and at the end of a study period of 8 weeks. In Herd 2 and 3 toltrazuril treated calves gained on average 7.95 kg more than placebo treated calves (p = 0.007), and both oocyst excretion and prevalence of Eimeria spp. were significantly reduced the first weeks post treatment. In Herd 1, by contrast, the farmer made some unforeseen changes in the management which entailed relocation to large deep-litter pens 3 - 6 weeks post treatment. In addition, many calves were not treated metaphylactically while few calves excreted oocysts when the trial was initiated. Thus, no significant difference in weight gain was found between toltrazuril and placebo treated calves (p = 0.523), and the oocyst excretion of toltrazuril treated calves was significantly higher during week 7 and 8. Significant differences in faecal scores were observed between the herds (p<0.002) but not between treatment groups in any of the herds. In conclusion, timing of treatment is crucial for optimal effect of metaphylactic toltrazuril treatment on weight gain and oocyst excretion. PMID- 26152423 TI - Functional analysis of a novel cysteine-rich antimicrobial peptide from the salivary glands of the tick Rhipicephalus haemaphysaloides. AB - Ticks encounter various microbes while sucking blood from an infected host and carrying these pathogens in themselves. Ticks can then transmit these pathogens to vertebrate hosts. The immune system of ticks can be stimulated to produce many bioactive molecules during feeding and pathogen invasion. Antimicrobial peptides (AMPs) are key effector molecules of a tick's immune response, as they can kill invading pathogenic microorganisms. In this study, we identified a novel cysteine rich AMP, designated Rhamp1, in the salivary glands of unfed and fed female ticks (Rhipicephalus haemaphysaloides). Rhamp1 is encoded by a gene with an open reading frame of 333 bp, which in turn encodes a peptide of 12 kDa with a 22 amino acid residue signal peptide. The Rhamp1 protein had a pI of 8.6 and contained six conserved cysteine residues at the C-terminus. Rhamp1 shared 43% amino acid identity with a secreted cysteine-rich protein of another tick species, Ixodes scapularis. We cloned the Rhamp1 gene and attempted to express a recombinant protein using prokaryotic and eukaryotic systems, to determine its biological significance. Recombinant Rhamp1 was successfully expressed in both systems, yielding a glutathione S-transferase (GST)-tagged protein (36 kDa) from the prokaryotic system, and a polyhistidine-tagged Rhamp1 protein (14 kDa) from the eukaryotic system. Rhamp1 inhibited the activities of chymotrypsin (16%) and elastase (22%) and exerted low hemolytic activity. It also inhibited the growth of Gram-negative bacteria, including Pseudomonas aeruginosa (49%), Salmonella typhimurium (50%), and Escherichia coli (52%). Our findings suggest that Rhamp1 is a novel AMP in R. haemaphysaloides with the ability to inhibit proteinase activity. PMID- 26152425 TI - Novel 5-functionalized-pyrazoles: Synthesis, characterization and pharmacological screening. AB - In the present study a series of O-substituted pyrazoles 7(a-f) and N-substituted pyrazoles 9(a-f) were synthesized via phase-transfer catalyzed reaction of ethyl 5-(bromomethyl)-1,3-diphenyl-1H-pyrazole-4-carboxylate 5 with various oxygen and nitrogen containing compounds in presence of tetrabutylammonium bromide (TBAB) in THF. The compound 5 was obtained by the efficient bromination with N bromosuccinimide (NBS) in presence of a catalytic amount of azoiso-bis-butyro nitrile (AIBN) in refluxing CCl4. The synthesized compounds were evaluated for their in vitro antimicrobial and antidiabetic activity and were compared with standard drugs. Among the synthesized compounds, compound 9b emerged as an excellent antimicrobial and antidiabetic agent. Newly synthesized compounds were characterized by analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods. PMID- 26152426 TI - Structure activity relationship of C-2 ether substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-5). AB - Oxabicyclooctane linked novel bacterial topoisomerase inhibitors (NBTIs) are new class of recently reported broad-spectrum antibacterial agents. They target bacterial DNA gyrase and topoisomerase IV and bind to a site different than quinolones. They show no cross-resistance to known antibiotics and provide opportunity to combat drug-resistant bacteria. A structure activity relationship of the C-2 substituted ether analogs of 1,5-naphthyridine oxabicyclooctane-linked NBTIs are described. Synthesis and antibacterial activities of a total of 63 analogs have been summarized representing alkyl, cyclo alkyl, fluoro alkyl, hydroxy alkyl, amino alkyl, and carboxyl alkyl ethers. All compounds were tested against three key strains each of Gram-positive and Gram-negative bacteria as well as for hERG binding activities. Many key compounds were also tested for the functional hERG activity. Six compounds were evaluated for efficacy in a murine bacteremia model of Staphylococcus aureus infection. Significant tolerance for the ether substitution (including polar groups such as amino and carboxyl) at C-2 was observed for S. aureus activity however the same was not true for Enterococcus faecium and Gram-negative strains. Reduced clogD generally showed reduced hERG activity and improved in vivo efficacy but was generally associated with decreased overall potency. One of the best compounds was hydroxy propyl ether (16), which mainly retained the potency, spectrum and in vivo efficacy of AM8085 associated with the decreased hERG activity and improved physical property. PMID- 26152428 TI - Anticancer effect and mechanism of a Se-modified porphyrin Au(III) complex. AB - Au, Se and porphyrin are widely used components in the design of anticancer drugs, but their combination has never been referred to. In this work, a Se modified porphyrin Au(III) complex, [AuTPP-Se]Cl, was designed and synthesized as a potential anticancer agent. This compound exhibits remarkable antiproliferative activity on all the six tested cancer cells. Its potency on HepG2 is even ten times higher than that of CDDP. The synergistic action among Au, Se and porphyrin components was validated. Mechanism study showed that both the induction of mitochondria-dependent apoptosis and the arrest of cell cycle contribute to the anticancer activity of [AuTPP-Se]Cl. PMID- 26152427 TI - A multifunctional, light-activated prochelator inhibits UVA-induced oxidative stress. AB - UVA radiation can damage cells and tissues by direct photodamage of biomolecules as well as by initiating metal-catalyzed oxidative stress. In order to alleviate both concerns simultaneously, we synthesized a multifunctional prochelator PC HAPI (2-((E)-1-(2-isonicotinoylhydrazono)ethyl)phenyl (trans)-3-(2,4 dihydroxyphenyl)acrylate) that contains a trans-(o-hydroxy)cinnamate ester photocleavable protecting group that is cleaved upon UVA exposure to release a coumarin, umbelliferone, and an aroylhydrazone metal chelator, HAPI (N'-[1-(2 hydroxyphenyl)ethyliden]isonicotinoylhydrazide). While the prochelator PC-HAPI exhibits negligible affinity for iron, it responds rapidly to UVA irradiation and converts to an iron-binding chelator that inhibits iron-catalyzed formation of reactive oxygen species and protects cells from UVA damage. PMID- 26152429 TI - Structure-activity relationship studies of QS11, a small molecule Wnt synergistic agonist. AB - Both the Wnt/beta-catenin signaling pathway and small GTPases of the ADP ribosylation factors (ARF) family play important roles in regulating cell development, homeostasis and fate. The previous report of QS11, a small molecule Wnt synergist that binds to ARF GTPase-activating protein 1 (ARFGAP1), suggests a role for ARFGAP1 in the Wnt/beta-catenin pathway. However, direct inhibition of enzymatic activity of ARFGAP1 by QS11 has not been established. Whether ARFGAP1 is the only target that contributes to QS11's Wnt synergy is also not clear. Here we present structure-activity relationship (SAR) studies of QS11 analogs in two assays: direct inhibition of enzymatic activity of purified ARFGAP1 protein and cellular activation of the Wnt/beta-catenin pathway. The results confirm the direct inhibition of ARFGAP1 by QS11, and also suggest the presence of other potential cellular targets of QS11. PMID- 26152430 TI - Antiproliferative and tumor inhibitory studies of 2,3 disubstituted 4 thiazolidinone derivatives. AB - 4-Thiazolidinone derivatives were synthesized using T3P(r)-DMSO media as a cyclodehydrating agent. All the molecules were tested for their cytotoxicity against leukemic cell lines. The compound 3-(4-bromophenyl)-2-(4 (dimethylamino)phenyl)thiazolidin-4-one (4e) with electron donating substituent at para position of phenyl ring displayed considerable cytotoxicity against Reh and Nalm6 cells with an IC50 value of 11.9 and 13.5 MUM, respectively. Furthermore, the compound 4e tested for tumor regression studies induced by EAC in Swiss albino mouse. Both in vitro and in vivo results suggested significant antiproliferative activity of compound 4e in Reh cells and mouse tumor tissue treated with compound 4e showed multifocal areas of necrosis and numerous number of apoptotic cells. PMID- 26152431 TI - Timely and/or Controversial Information for Family Physicians. AB - Plan to spend some time reading this information-dense issue with a large amount of new material and ideas. From the humanoid behavioral health coach to tackling the controversial topic of environmental causes of autism spectrum disorders, this issue encompasses a broad range of topics. New anticoagulants for an extremely common entity, atrial fibrillation, are discussed. Learn about the shocking increase in oropharyngeal cancers with a changing epidemiology: younger patients with a different clinical presentations. Researchers evaluate changes after new or revised guidelines. "Near miss" reporting can facilitate quality improvement. Pets can make humans ill, yet they are beloved and can improve the health of their human owners. PMID- 26152432 TI - Agency for Healthcare Research and Quality (AHRQ) Webinar Features 3 Journal of American Board of Family Medicine Practice-based Research (PBR) Articles. PMID- 26152433 TI - A Significant Number of Charter Diplomates Participate in American Board of Family Medicine (ABFM) Maintenance of Certification. AB - Considerable controversy about the value of participating in Maintenance of Certification has recently arisen within the medical community. Despite this controversy, large numbers of family physicians certified by the American Board of Family Medicine participate in Maintenance of Certification for Family Physicians. Surprisingly, a small but significant number of charter diplomats- those initially certified by the American Board of Family Medicine at its founding--are engaged in the process. PMID- 26152434 TI - Reducing Preconception Risks Among African American Women with Conversational Agent Technology. AB - BACKGROUND: Systems and tools are needed to identify and mitigate preconception health (PCH) risks, particularly for African American (AA) women, given persistent health disparities. We developed and tested "Gabby," an online preconception conversational agent system. METHODS: One hundred nongravid AA women 18-34 years of age were screened for over 100 PCH risks and randomized to the Gabby or control group. The Gabby group interacted with the system for up to six months; the control group received a letter indicating their health risks with a recommendation to talk with their clinician. The numbers, proportions, and types of risks were compared between groups. RESULTS: There were 23.7 (SD 5.9) risks identified per participant. Eighty-five percent (77 of 91) provided 6 month follow up data. The Gabby group had greater reductions in the number (8.3 vs. 5.5 risks, P < .05) and the proportion (27.8% vs 20.5%, P < 0.01) of risks compared to controls. The Gabby group averaged 63.7 minutes of interaction time. Seventy eight percent reported that it "was easy to talk to Gabby" and 64% used information from Gabby to improve their health. CONCLUSION: Gabby was significantly associated with preconception risk reduction. More research is needed to determine if Gabby can benefit higher risk populations and if risk reduction is clinically significant. PMID- 26152435 TI - Reporting and Using Near-miss Events to Improve Patient Safety in Diverse Primary Care Practices: A Collaborative Approach to Learning from Our Mistakes. AB - PURPOSE: Near-miss events represent an opportunity to identify and correct errors that jeopardize patient safety. This study was undertaken to assess the feasibility of a near-miss reporting system in primary care practices and to describe initial reports and practice responses to them. METHODS: We implemented a web-based, anonymous near-miss reporting system into 7 diverse practices, collecting and categorizing all reports. At the end of the study period, we interviewed practice leaders to determine how the near-miss reports were used for quality improvement (QI) in each practice. RESULTS: All 7 practices successfully implemented the system, reporting 632 near-miss events in 9 months and initiating 32 QI projects based on the reports. The most frequent events reported were breakdowns in office processes (47.3%); of these, filing errors were most common, with 38% of these errors judged by external coders to be high risk for an adverse event. Electronic medical records were the primary or secondary cause of the error in 7.8% and 14.4% of reported cases, respectively. The pattern of near-miss events across these diverse practices was similar. CONCLUSIONS: Anonymous near miss reporting can be successfully implemented in primary care practices. Near miss events occur frequently in office practice, primarily involve administrative and communication problems, and can pose a serious threat to patient safety; they can, however, be used by practice leaders to implement QI changes. PMID- 26152436 TI - Maternal Chemical and Drug Intolerances: Potential Risk Factors for Autism and Attention Deficit Hyperactivity Disorder (ADHD). AB - PURPOSE: The aim of this study was to assess whether chemically intolerant women are at greater risk for having a child with autism spectrum disorders (ASD) or attention deficit hyperactivity disorder (ADHD). METHODS: We conducted a case control study of chemical intolerance among mothers of children with ASD (n = 282) or ADHD (n = 258) and children without these disorders (n = 154). Mothers participated in an online survey consisting of a validated chemical intolerance screening instrument, the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Cases and controls were characterized by parental report of a professional diagnosis. We used a one-way, unbalanced analysis of variance to compare means across the 3 groups. RESULTS: Both mothers of children with ASD or ADHD had significantly higher mean chemical intolerance scores than did mothers of controls, and they were more likely to report adverse reactions to drugs. Chemically intolerant mothers were 3 times more likely (odds ratio, 3.01; 95% confidence interval, 1.50-6.02) to report having a child with autism or 2.3 times more likely (odds ratio, 2.3; 95% confidence interval, 1.12-5.04) to report a child with ADHD. Relative to controls, these mothers report their children are more prone to allergies (P < .02), have strong food preferences or cravings (P < .003), and have greater sensitivity to noxious odors (P < .04). CONCLUSION: These findings suggest a potential association between maternal chemical intolerance and a diagnosis of ADHD or ASD in their offspring. PMID- 26152437 TI - Clinical Decisions Made in Primary Care Clinics Before and After Choosing Wisely. AB - BACKGROUND: The Choosing Wisely campaign encourages physicians to avoid low-value care. Although widely lauded, no study has examined its impact on clinical decisions made in primary care settings. METHODS: We compared clinical decisions made for 5 Choosing Wisely recommendations over two 6-month time periods before and after the campaign launch and an educational intervention to promote it at 3 primary care residency clinics. RESULTS: The rate of recommendations adherence was high (93.2%) at baseline but did significantly increase to 96.5% after the launch. These findings suggest primary care physicians respond to training and publicity in low-value care, though further research is needed. CONCLUSION: Given that even small decreases of physician test ordering can produce large cost savings, the Choosing Wisely project may help achieve the health care triple aim. PMID- 26152438 TI - Patient Understanding of Body Mass Index (BMI) in Primary Care Practices: A Two State Practice-based Research (PBR) Collaboration. AB - BACKGROUND: The concept of body mass index (BMI) may not be well understood by patients. The purpose of this study was to evaluate patients' knowledge of BMI in the primary care setting. METHODS: Adult patients seen in 18 practices in West Virginia and New Jersey were invited to complete a voluntary survey. The survey assessed the patient's baseline knowledge of BMI as well as demographic information and whether the patient had known chronic conditions associated with increased BMI, including hypertension, hyperlipidemia, diabetes mellitus, and sleep apnea. RESULTS: While the majority (59.9%) of primary care patients knew the meaning of BMI and that it is related to obesity, there was little knowledge of BMI cutoff values; more than 80% of responses were incorrect when asked to define specific BMI levels and their meaning. Self-awareness of obesity was limited as well, with only 16.4% aware of their own personal BMI. Furthermore, nearly 70% of patients could not recall having discussed BMI with their physician. CONCLUSION: Findings indicate low comprehension of the term BMI. Increasing awareness of BMI may help patients address this key risk factor and significantly affect public health. PMID- 26152439 TI - Regional Supply of Chiropractic Care and Visits to Primary Care Physicians for Back and Neck Pain. AB - BACKGROUND: Whether availability of chiropractic care affects use of primary care physician (PCP) services is unknown. METHODS: We performed a cross-sectional study of 17.7 million older adults who were enrolled in Medicare from 2010 to 2011. We examined the relationship between regional supply of chiropractic care and PCP services using Spearman correlation. Generalized linear models were used to examine the association between regional supply of chiropractic care and number of annual visits to PCPs for back and/or neck pain. RESULTS: We found a positive association between regional supply of chiropractic care and PCP services (rs = 0.52; P <.001). An inverse association between supply of chiropractic care and the number of annual visits to PCPs for back and/or neck pain was apparent. The number of PCP visits for back and/or neck pain was 8% lower (rate ratio, 0.92; 95% confidence interval, 0.91-0.92) in the quintile with the highest supply of chiropractic care compared to the lowest quintile. We estimate chiropractic care is associated with a reduction of 0.37 million visits to PCPs nationally, at a cost of $83.5 million. CONCLUSIONS: Greater availability of chiropractic care in some areas may be offsetting PCP services for back and/or neck pain among older adults. PMID- 26152440 TI - Decrease in Prostate Cancer Testing Following the US Preventive Services Task Force (USPSTF) Recommendations. AB - PURPOSE: To assess changes of prostate-specific antigen (PSA) testing following recent US Preventive Services Task Force (USPSTF) prostate cancer screening recommendations using 2005 to 2013 National Health Interview Survey data. METHODS: We calculated the percentage of PSA testing among men >=40 years by age group and age-adjusted race for each survey year. Differences between years were assessed with linear contrasts after combining all years' data. RESULTS: The overall percentage of PSA testing was highest in 2008 and decreased significantly in 2013. Compared with 2008, each age group had significantly lower screening percentages in 2013, especially men >=75 years old (-14.0% points; P < .001). Both men aged 50 to 74 and men aged >=75 had significantly lower percentages in 2013 than in 2010. For white and black men, the PSA testing percentages were highest in 2008 and decreased significantly in 2013. Only white men had a significantly lower percentage in 2013 than in 2010. CONCLUSIONS: Significant declines in PSA testing from 2008 to 2013 in men >=75 years old may reflect the impact of the 2008 USPSTF recommendations. While the cause of the decreases in PSA testing between 2010 and 2013 among men aged 50 to 74 years old and white men is unknown, the decreases may suggest the early effects of the 2012 recommendations. PMID- 26152441 TI - Veterans' Continued Participation in an Annual Fecal Immunochemical Test Mailing Program for Colorectal Cancer Screening. AB - OBJECTIVE: The objective of this study was to determine what proportion of veterans previously screened for colorectal cancer (CRC) using fecal immunochemical testing (FIT) would be willing to undergo a second round of FIT screening. METHODS: Patients in the Iowa City Veterans Affairs Health Care System (<65 years old, asymptomatic, average risk, overdue for CRC screening) who completed a mailed FIT (April 2011 to May 2012) were contacted 1 year later by telephone to collect demographic and recent CRC screening information, and were offered a second mailed FIT if eligible. RESULTS: Of 204 veterans who completed initial FIT testing, 159 were eligible to participate in a second round of FIT screening; 132 (83%) participated in the telephone survey, and 126 (79%) completed a second annual FIT, with 10 (8%) individuals testing positive. The majority of participants (67%) reported being more likely to take a yearly FIT than a colonoscopy every 10 years. Participants overwhelmingly reported that the FIT was easy to use and convenient (89%), and they were likely to complete a mailed FIT each year (97%). CONCLUSIONS: Those willing to take a mailed FIT seem satisfied with this method and willing to do it annually. Population-based or provider-based FIT mailing programs have the potential to increase CRC screening in overdue populations. PMID- 26152442 TI - The Growing Epidemic of HPV-Positive Oropharyngeal Carcinoma: A Clinical Review for Primary Care Providers. AB - While the rate of head and neck cancer has decreased in recent decades, the prevalence of oropharynx cancer has dramatically increased due to human papillomavirus (HPV)-related oropharyngeal cancer. Three of 4 newly diagnosed oropharyngeal carcinomas are HPV-positive, and by 2020 it is projected that the prevalence of this disease will overtake that of HPV-related cervical cancer. Recognized in recent years as a malignant entity distinct from HPV-negative oropharyngeal carcinoma, HPV-positive oropharyngeal cancer is associated with younger age at diagnosis, oral sexual behavior as a primary risk factor, nonspecific presentation, and improved treatment response compared with HPV negative disease. Early recognition and referral for definitive treatment are paramount in decreasing morbidity and mortality, as well as improving the quality of life of these patients. Primary care providers are in an ideal position to improve patient outcomes through early recognition and referral, as well as coordination of comprehensive care of patients with this potentially devastating disease. Awareness of risk factors, a high index of suspicion, counseling patients and parents on the importance of vaccination against HPV, and coordinated care between primary care providers and specialists are vital to achieving improved outcomes for patients with this increasingly prevalent cancer. PMID- 26152443 TI - Home Sleep Tests for Obstructive Sleep Apnea (OSA). AB - Obstructive sleep apnea (OSA) is a fairly common condition that, if left untreated, can lead to complications such as high blood pressure and heart disease. Polysomnography (PSG) is the most accurate method for diagnosing OSA, but it is a cumbersome and expensive test. A well-validated, easier to perform and less expensive alternative is the home sleep test (HST). The purpose of this review is to educate the primary care provider about the important differences between PSG and HSTs, the advantages and limitations of both modalities, identifying patients who are appropriate candidates for the HST, identifying patients in whom the HST should not be performed, and further evaluation of patients who have a negative HST. PMID- 26152444 TI - Novel Anticoagulants in Atrial Fibrillation: A Primer for the Primary Physician. AB - Atrial fibrillation is a common arrhythmia encountered in clinical practice. The prevalence increases with age. A devastating complication of atrial fibrillation is cardioembolic stroke with central nervous system sequelae. Based on stroke risk scores (CHADS and CHA2DS2VASc) and bleeding risk (HAS-BLED), the optimal use of anticoagulation in atrial fibrillation is feasible. Warfarin is a proven medication for this specific indication but requires frequent monitoring and dose adjustments, and it has multiple food, drug, and disease-state interactions. In addition, management of anticoagulation during the perioperative period may be challenging. In this regard, novel oral anticoagulants (NOACs) have shown promise in the shift toward the "ideal" anticoagulant therapy, in that fixed dosing is the norm, drug interactions are few, food interactions are absent, onset is fairly immediate and offset predictable, and, in the majority of patients, therapeutic monitoring is not required. This article provides a review of recent published trials of the use of NOACs in atrial fibrillation. Practical points on indications, contraindications, mechanism of action, interactions, and perioperative management tips are discussed with a view toward the safe and effective use of these new medications. When patients are transitioned between different anticoagulant medications, the risks of thrombosis and bleeding need to be considered. When switching from warfarin to a NOAC, the NOAC can be started once the international normalized ratio is <=2.0. PMID- 26152445 TI - Obtaining an Adequate Specimen for the Diagnosis of Pigmented Lesions. AB - Melanoma is a common, potentially deadly disease but is curable if caught early. A specimen of a pigmented lesion must capture the entire width and depth of the lesion to evaluate the lesion's size, symmetry, and circumscription. Saucerization shaving, punching, and excision biopsy are 3 techniques that can be used to achieve a satisfactory specimen. Physicians should have a low threshold to biopsy a suspicious atypical pigmented lesion, but acceptable specimens are key in following through with an accurate diagnosis. PMID- 26152446 TI - Pets' Impact on Your Patients' Health: Leveraging Benefits and Mitigating Risk. AB - Over two thirds of Americans live with pets and consider them important members of the family. Pets benefit human health (zooeyia) in 4 ways: as builders of social capital, as agents of harm reduction, as motivators for healthy behavior change, and as potential participants in treatment plans. Conversely, pets can present risks to their owners. They are potential sources of zoonotic disease and injury. Pets can also challenge a family's prioritization of financial and social resources. To activate the benefits of zooeyia and appropriately calibrate and mitigate zoonotic risk, physicians first need to know about the pets in their patients' families. Asking about pets is a simple and feasible approach to assess patients' environmental history and social capital. Asking about pets is a nonthreatening way to build rapport and demonstrates an interest in the whole family, which can improve the physician-patient therapeutic alliance. Physicians can use an interprofessional, collaborative approach with veterinarians to address zoonotic health risks and leverage zooeyia. PMID- 26152447 TI - Birthing and Family Medicine: More Than Obstetrics. AB - The term birth injury usually applies to an injury sustained by either a woman or her infant in the course of giving birth. In this case the injury was sustained by the delivering family physician. What initially seemed like a minor injury turned out to require a significant career modification. The writer reflects on the personal impact of his choice to provide maternity care as a family physician. The unexpected end to this part of his practice, brought on by the injury, allows an opportunity to assess the effect of other "birth" experiences that are inherent to long-term patient-doctor relationships in family medicine. PMID- 26152448 TI - Re: Performance on the Maintenance of Certification for Family Physicians (MC-FP) Examination: Comparison of Initial Certifiers with Experienced Physicians. PMID- 26152449 TI - Utility of rotational atherectomy and outcomes over an eight-year period. AB - OBJECTIVES: To evaluate outcomes of patients undergoing rotational atherectomy (RA) in a multicenter percutaneous coronary intervention (PCI) registry. BACKGROUND: RA remains an important technique for plaque modification in PCI, particularly with complex calcification. METHODS: The study population consisted of consecutive patients undergoing PCI in nine major Australian hospitals, who were treated over an 8-year period (June 2004 to June 2012). RESULTS: Of 16,577 PCI's, 1.0% of patients n = 167 (214 lesions) underwent RA. Patients undergoing RA were more likely to be older (71.0 +/- 9.7 vs. 64.4 +/-11.9 years, P < 0.01), with greater incidence of diabetes (37.7% vs. 23.8%, P < 0.01) and renal impairment. There was no significant difference in procedural success (94.6% vs. 95.5%, P = 0.57), dissection (6.1% vs. 4.8%, P = 0.39), transient no reflow (4.4% vs. 2.8%, P = 0.23), or persistent no reflow (0% RA vs. 0.7% non-RA, P = 0.23). Those undergoing RA had a low but increased risk of death at 12 months (6.6 vs. 3.6%, P = 0.04). There was no significant difference in 12 month major adverse cardiovascular outcomes (MACE) between groups following adjustment for univariate predictors (OR 1.00, 95%CI; 0.93-1.08). Additionally, there was no significant difference in 30-day MACE (6.0% vs. 5.1%, P = 0.62) or 30-day mortality (2.4% vs. 1.8%, P = 0.54) between groups. CONCLUSIONS: In this large multicenter registry, RA continues to be used to treat complex lesions with low procedural complications and MACE rates. It is essential for interventional cardiologists to maintain skills in RA to enable effective percutaneous treatment of certain complex lesions. PMID- 26152450 TI - The relationship between internet addiction and eating disorders. PMID- 26152451 TI - Mentalization in eating disorders: a preliminary trial comparing mentalization based treatment (MBT) with a psychodynamic-oriented treatment. PMID- 26152452 TI - Long-term maintenance of a microfluidic 3D human liver sinusoid. AB - The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a chip, using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic) and urea excretion (detoxification) were observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies. PMID- 26152453 TI - Aerial projection of three-dimensional motion pictures by electro-holography and parabolic mirrors. AB - We demonstrate an aerial projection system for reconstructing 3D motion pictures based on holography. The system consists of an optical source, a spatial light modulator corresponding to a display and two parabolic mirrors. The spatial light modulator displays holograms calculated by computer and can reconstruct holographic motion pictures near the surface of the modulator. The two parabolic mirrors can project floating 3D images of the motion pictures formed by the spatial light modulator without mechanical scanning or rotating. In this demonstration, we used a phase-modulation-type spatial light modulator. The number of pixels and the pixel pitch of the modulator were 1,080 * 1,920 and 8.0 MUm * 8.0 MUm, respectively. The diameter, the height and the focal length of each parabolic mirror were 288 mm, 55 mm and 100 mm, respectively. We succeeded in aerially projecting 3D motion pictures of size ~2.5 mm(3) by this system constructed by the modulator and mirrors. In addition, by applying a fast computational algorithm for holograms, we achieved hologram calculations at ~12 ms per hologram with 4 CPU cores. PMID- 26152454 TI - Nitrous oxide and methane emissions from cryptogamic covers. AB - Cryptogamic covers, which comprise some of the oldest forms of terrestrial life on Earth (Lenton & Huntingford, ), have recently been found to fix large amounts of nitrogen and carbon dioxide from the atmosphere (Elbert et al., ). Here we show that they are also greenhouse gas sources with large nitrous oxide (N2 O) and small methane (CH4 ) emissions. Whilst N2 O emission rates varied with temperature, humidity, and N deposition, an almost constant ratio with respect to respiratory CO2 emissions was observed for numerous lichens and bryophytes. We employed this ratio together with respiration data to calculate global and regional N2 O emissions. If our laboratory measurements are typical for lichens and bryophytes living on ground and plant surfaces and scaled on a global basis, we estimate a N2 O source strength of 0.32-0.59 Tg year(-1) for the global N2 O emissions from cryptogamic covers. Thus, our emission estimate might account for 4-9% of the global N2 O budget from natural terrestrial sources. In a wide range of arid and forested regions, cryptogamic covers appear to be the dominant source of N2 O. We suggest that greenhouse gas emissions associated with this source might increase in the course of global change due to higher temperatures and enhanced nitrogen deposition. PMID- 26152455 TI - A case report of undiagnosed postpartum hemolytic uremic syndrome. AB - BACKGROUND: Postpartum hemolytic uremic syndrome (PHUS) is a severe thrombotic microangiopathy (TMA) that is clinically characterized by hemolytic anemia, renal dysfunction, and low platelet levels after childbirth. Here, we report a rare case of unexpected death due to PHUS. CASE PRESENTATION: A 23-year-old parturient had an uncomplicated cesarean section at 40 weeks gestation. The immediate postpartum course was uneventful. However, eight days post delivery, the patient developed severe nausea and vomiting followed by hematuria, spontaneous bruising, marked pallor, icteric sclera, and lethargy. Laboratory findings revealed that the patient had hemolytic anemia, thrombocytopenia, and acute renal failure. This patient died approximately 29 h after the onset of symptoms. Post-mortem examination confirmed that the patient had PHUS. CONCLUSIONS: This paper addresses the need for a renal histological examination in addition to a thorough clinical history and appropriate laboratory tests for the rapid and accurate diagnosis of PHUS. Early detection and diagnosis can significantly improve the prognosis and optimize maternal outcomes. PMID- 26152456 TI - Hand eczema and atopic dermatitis in adolescents: a prospective cohort study from the BAMSE project. AB - BACKGROUND: There is a well-known association between atopic dermatitis (AD) and hand eczema but less is known about how age at onset, persistence and severity of AD influence the risk of developing hand eczema. OBJECTIVES: To examine the role of AD in the occurrence of hand eczema in adolescence. In addition, associations between asthma and rhinoconjunctivitis, sensitization to common airborne and food allergens, and hand eczema were studied. METHODS: From the population-based birth cohort BAMSE, 2927 adolescents who had been followed up repeatedly concerning allergy-related disease were included. Questionnaires identified adolescents with hand eczema at 16 years, and their blood was analysed for specific IgE. RESULTS: A total of 152 (5.2%) adolescents had hand eczema at the age of 16 years. Many of these adolescents had a history of AD (n = 111; 73.0%) and asthma and/or rhinitis (n = 83; 54.6%), respectively. Children with AD (aged 0-16 years) had more than threefold increased odds ratios (OR) for having hand eczema; those with persistent or severe AD had a crude OR of 6.1 [95% confidence interval (CI) 4.0 9.1] and 5.3 (95% CI 2.9-9.6), respectively. CONCLUSIONS: We confirm a strong association between AD during childhood and hand eczema in adolescence. Children with persistent or more severe AD are at greater risk of developing hand eczema. Asthma and/or rhinoconjunctivitis, positive specific IgE or age at onset of AD are not associated with hand eczema in adolescence. PMID- 26152457 TI - Primary breast cancer induces pulmonary vascular hyperpermeability and promotes metastasis via the VEGF-PKC pathway. AB - The lung is one of the most frequent target organs for breast cancer metastasis. When breast cancer cells from a primary tumor do not colonize the lung, which we named the premetastatic phase, the microenvironment of the lung has already been influenced by the primary tumor. However, little is known about the exact premetastatic alteration and regulatory mechanisms of the lung. Here, we used 4T1 cells (a mouse breast cancer cell line which can specifically metastasize to the lung) to build a mouse breast cancer model. We found that primary breast tumor induced increased pulmonary vascular permeability in the premetastatic phase, which facilitated the leakage of rhodamine-dextran and the extravasation of intravenous therapy injected cancer cells. Furthermore, tight junctions (TJs) were disrupted, and the expression of zonula occludens-1(ZO-1), one of the most important components of tight junctions, was decreased in the premetastatic lung. In addition, elevated serum vascular endothelial growth factor (VEGF) was involved in the destabilization of tight junctions and the VEGF antagonist bevacizumab reversed the primary tumor-induced vascular hyperpermeability. Moreover, activation of the protein kinase C (PKC) pathway disrupted the integrity of TJs and accordingly, the disruption could be alleviated by blocking VEGF. Taken together, these data demonstrate that primary breast cancer may induce tight junction disruptions in the premetastatic lung via the VEGF-PKC pathway and promote pulmonary vascular hyperpermeability before metastasis. (c) 2015 Wiley Periodicals, Inc. PMID- 26152458 TI - Triple-positive pathologic findings in oral cavity cancer are related to a dismal prognosis. AB - OBJECTIVES/HYPOTHESIS: Perineural invasion (PNI), lymphovascular invasion (LVI), and extracapsular spread (ECS) of lymph nodes are adverse histopathologic factors among patients with oral cancer. We analyzed the clinical impact of the combination of PNI, LVI, and ECS among patients with oral cancer. STUDY DESIGN: Retrospective analysis of patients with oral cancer that was treated primarily with surgery with at least 5 years of follow-up data in a tertiary referral center. METHODS: In total, 554 patients diagnosed with oral cavity squamous cell carcinoma who underwent operations consecutively between 2006 and 2008 in our hospital were enrolled. Clinical characteristics, 5-year survival rates, and local/regional control rates were analyzed. RESULTS: There were 41 females and 513 males. Patients with PNI, LVI, or ECS presented pathologically had 5-year overall survival rates of 58.4%, 50.4%, and 31.4%, respectively. Patients with both ECS and PNI or both ECS and LVI presented had 5-year overall survival rates of 31.5% and 22.2%, respectively. Patients presenting with triple-positive status (PNI, LVI, and ECS) had only a 20.0% 5-year overall survival rate. The 5-year local/regional control rate for patients with both ECS and PNI or both ECS and LVI was 26% and 44.4%, respectively; for all three factors, it was 26.7%. CONCLUSION: Patients with triple-positive status (PNI, LVI, ECS), ECS and PNI, or ECS and LVI experienced very low 5-year local/regional control rates, 5-year overall, and disease-specific survival rates. Novel interventions are necessary to improve these clinical outcomes. LEVEL OF EVIDENCE: 4. PMID- 26152459 TI - Interspecific competition between Snellenius manilae and Meteorus pulchricornis, larval parasitoids of Spodoptera litura. AB - Snellenius manilae (Ashmead) and Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae) are larval endoparasitoids of Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae). Both species preferentially parasitize early-instar S. litura and occupy similar ecological niches. Therefore, competition between the two species may occur. In this study, intrinsic competition and cage experiments were conducted to discuss the interactions between S. manilae and M. pulchricornis. The results indicated that in intrinsic competition, M. pulchricornis was always the dominant species. In cage experiments, when the total number of parasitoids was four, the parasitism rates following the release of one species were significantly higher than the release of two species simultaneously. In addition, parasitism rate of eight M. pulchricornis was also significantly higher than the parasitism rate of the treatment released four S. manilae and four M. pulchricornis simultaneously. Therefore, competition occurs between S. manilae and M. pulchricornis, and M. pulchricornis is typically the superior of the two species. The use of M. pulchricornis as a biological agent for S. litura should be considered. PMID- 26152460 TI - Cu(I)/Rh(II)-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of gamma-Oxo-beta-amino Esters. AB - The first example of a highly regio- and stereoselective catalytic method for the three-component one-pot synthesis of highly functionalized alpha-vinylated gamma oxo-beta-amino esters is disclosed. In this catalytic triad, the Cu(I)-catalyst selectively catalyzes the cycloaddition of the 1-alkyne and sulfonyl azide first resulting in the corresponding 1-sulfonyl-1,2,3-triazole. An alpha-imino Rh(II) carbene is generated from an open-chain alpha-imino diazo of the triazole, and this species reacts with gamma-hydroxy alpha,beta-unsaturated esters to form allylic (Z)-amino vinyl ethers. Rapid deconjugative [3,3]-sigmatropic rearrangement affords the alpha-vinyl gamma-oxo-beta-amino esters in high yields with high levels of diastereoselectivity. PMID- 26152461 TI - Quantification of loading in biomechanical testing: the influence of dissection sequence. AB - Sequential dissection is a technique used to investigate loads experienced by articular tissues. When the joint of interest is tested in an unconstrained manner, its kinematics change with each tissue removal. To address this limitation, sufficiently rigid robots are used to constrain joint kinematics. While this approach can quantify loads experienced by each tissue, it does not assure similar results when removal order is changed. Specifically, structure loading is assumed to be independent of removal order if the structure behaves linearly (i.e. principle of superposition applies), but dependent on removal order when response is affected by material and/or geometry nonlinearities and/or viscoelasticiy (e.g. biological tissues). Therefore, this experiment was conducted to evaluate if structure loading created through robotic testing is dependent on the order in which connectors are removed. Six identical models were 3D printed. Each model was composed of 2 rigid bodies and 3 connecting structures with nonlinear time-dependent behavior. To these models, pure rotations were applied about a predefined static center of rotation using a parallel robot. A unique dissection sequence was used for each of the six models and the same movements applied robotically after each dissection. When comparing the moments experienced by each structure between different removal sequences, a statistically significant difference (p<0.05) was observed. These results suggest that even in an optimized environment, the sequence in which nonlinear viscoelastic structures are removed influence model loading. These findings support prior work suggesting that tissue loads obtained from robotic testing are specific to removal order. PMID- 26152462 TI - Possibilities and limitations of novel in-vitro knee simulator. AB - The ex-vivo evaluation of knee kinematics remains vital to understand the impact of surgical treatments such as total knee arthroplasty (TKA). To that extent, knee simulators have been developed. However, these simulators have mainly focused on the simulation of a squatting motion. The relevance of this motion pattern for patients' activities of daily living is however questionable as squatting is difficult for elderly patients. Walking, stairs and cycling are more relevant motion patterns. This paper presents the design and control of a simulator that allows to independently control the applied kinematic and kinetic boundary conditions to simulate these daily life activities. Thereby, the knee is left with five degrees of freedom; only the knee flexion is actively controlled. From a kinetic point of view, the quadriceps and hamstring muscles are loaded. Optionally, a varus/valgus moment can be applied, facilitating a dynamic evaluation of the knee's stability. The simulator is based on three control loops, whose synchronization appears satisfactory. The input for these control loops can be determined from either musculoskeletal simulations or in accordance to literature data for traditional knee simulators. This opens the door towards an improved understanding of the knee biomechanics and comparison between different applied motion and force patterns. PMID- 26152463 TI - Monitoring recovery of gait balance control following concussion using an accelerometer. AB - Despite medical best-practice recommendations, no consistent standard exists to systematically monitor recovery from concussion. Studies utilizing camera-based systems have reported center-of-mass (COM) motion control deficits persisting in individuals with concussion up to two months post-injury. The use of an accelerometer may provide an efficient and sensitive method to monitor COM alterations following concussion that can be employed in clinical settings. This study examined: (1) frontal/sagittal plane acceleration characteristics during dual-task walking for individuals with concussion and healthy controls; and (2) the effectiveness of utilizing acceleration characteristics to classify concussed and healthy individuals via receiver operating characteristic (ROC) curve analyses. Individuals with concussion completed testing within 72 h as well as 1 week, 2 weeks, 1 month, and 2 months post-injury. Control subjects completed the same protocol in similar time increments. Participants walked and simultaneously completed a cognitive task while wearing an accelerometer attached to L5. Participants with concussion walked with significantly less peak medial-lateral acceleration during 55-75% gait cycle (p=0.04) throughout the testing period compared with controls. Moderate levels of sensitivity and specificity were found at the 72 h and 1 week testing times (sensitivity=0.70, specificity=0.71). ROC analysis revealed significant AUC values at the 72 h (AUC=0.889) and two week (AUC=0.810) time points. Accelerometer-derived measurements may assist in detecting frontal plane control deficits during dual-task walking post concussion, consistent with camera-based studies. These initial findings demonstrate potential for using accelerometry as a tool for clinicians to monitor gait balance control following concussion. PMID- 26152464 TI - Modulation of AQP-3 in burn wound: Comment on "Epidermal aquaporin-3 is increased in the cutaneous burn wound". PMID- 26152465 TI - Proteomic profiling of the extracellular matrix (slime sheath) of Dictyostelium discoideum. AB - Dictyostelium discoideum has historically served as a model system for cell and developmental biology, but recently it has gained increasing attention as a model for the study of human diseases. The extracellular matrix (ECM) of this eukaryotic microbe serves multiple essential functions during development. It not only provides structural integrity to the moving multicellular pseudoplasmodium, or slug, it also provides components that regulate cell motility and differentiation. An LC/MS/MS analysis of slug ECM revealed the presence of a large number of proteins in two wild-type strains, NC4 and WS380B. GO annotation identified a large number of proteins involved in some form of binding (e.g. protein, polysaccharide, cellulose, carbohydrate, ATP, cAMP, ion, lipid, vitamin), as well as proteins that modulate metabolic processes, cell movement, and multicellular development. In addition, this proteomic analysis identified numerous expected (e.g. EcmA, EcmD, discoidin I, discoidin II), as well as unexpected (e.g. ribosomal and nuclear proteins) components. These topics are discussed in terms of the structure and function of the ECM during the development of this model amoebozoan and their relevance to ongoing biomedical research. PMID- 26152466 TI - Evaluation of virulence factors and antifungal susceptibility patterns of different Candida species isolated from the female camel (Camelus dromedarius) genital tract. AB - The purposes of this study were to investigate the enzymatic activity of different Candida species and their antifungal susceptibility patterns. The study involved a total of 83 isolates of Candida from the genital tract of the female Camelus dromedarius. After species identification, the isolates were analysed for the production/activity of phospholipase, proteinase and haemolysin. In addition, the agar disc diffusion method was performed on the basis of CLSI guidelines M44 A2 protocol for antifungal susceptibility testing. All the isolates were able to produce phospholipase, proteinase and haemolysin. A total of 35.48%, 87.09% and 64.51% of C. albicans isolates exhibited very high phospholipase, proteinase and haemolytic activities, respectively, whereas very high phospholipase, proteinase and haemolytic activities were determined in 5.76%, 23.07% and 45.16% of non-C. albicans isolates respectively. Overall, 61 (73.5%) of Candida isolates were susceptible to fluconazole, 70 (84.3%) susceptible to clotrimazole, 82 (98.8%) susceptible to voriconazole, 76 (91.6%) susceptible to itraconazole, 75 (90.4%) susceptible to ketoconazole, 83 (100%) susceptible to amphotericin B, 81 (97.6%) susceptible to nystatin and 36 (43.4%) susceptible to flucytosine. Candida isolates showed higher haemolytic activity than that of other secreted hydrolases among vaginal Candida species. In addition, amphotericin B was the most in vitro effective antifungal drug and flucytosine had the poorest activity under such conditions. PMID- 26152467 TI - Internet Use for Health-Care Information by Subjects With COPD. AB - BACKGROUND: Although the internet is an important tool for entertainment, work, learning, shopping, and communication, it is also a possible source for information on health and disease. The aim of this study was to evaluate the proportion of subjects with COPD in Sao Paulo, Brazil, who use the internet to obtain information about their disease. METHODS: Subjects (N = 382) with COPD answered a 17-question survey, including information regarding computer use, internet access, and searching for sites on COPD. Our sample was distributed according to the socioeconomic levels of the Brazilian population (low, 17.8%; medium, 66.5%; and high, 15.7%). RESULTS: Most of the subjects in the sample were male (62.6%), with a mean age of 67.0 +/- 9.9 y. According to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, 74.3% of the subjects were in stage II or III. In addition, 51.6% of the subjects had a computer, 49.7% accessed the internet, and 13.9% used it to search for information about COPD. The internet was predominantly accessed by male (70.3%) and younger (64.6 +/- 9.5 y of age) subjects compared with female (29.7%, P = .04) and older (67.5 +/- 9.6 y of age, P < .007) subjects. Searching for information about COPD on the internet was associated with having a computer (5.9-fold), Medical Research Council dyspnea level 1 (5.3-fold), and high social class (8.4-fold). The search for information on COPD was not influenced by GOLD staging. CONCLUSIONS: A low percentage of subjects with COPD in Sao Paulo use the internet as a tool to obtain information about their disease. This search is associated with having a computer, low dyspnea score, and high socioeconomic level. PMID- 26152468 TI - Performance and Acceptability of Two Self-Inflating Bag-Mask Neonatal Resuscitator Designs. AB - BACKGROUND: A self-inflating bag-mask device is specified by international policy guidelines as standard prototype of care for newborn resuscitation. Our hypothesis is that a new bag-mask design would be as effective and easy to use as a standard, self-inflating resuscitation bag-mask. METHODS: We conducted a comparative evaluation of the performance and acceptability of the Laerdal 220-mL resuscitator with a size-1 mask (NeoNatalie) and a Laerdal prototype Upright resuscitator with a modified mask. Participants evaluated the devices in random order using a commercially available test lung and training mannikin with an integrated chest-rise module. The test lung was configured with healthy and sick newborn lung mechanics. Two user groups participated: (1) frequent users who had used manual resuscitators to resuscitate infants and (2) infrequent users who received competency-based training and had not previously used manual resuscitators to resuscitate infants. RESULTS: Thirty-eight individuals participated in the study during March 2013. Both resuscitators are capable of delivering the minimum required tidal volumes to newborns. The Upright device provided a significant reduction in the percentage of inadequate ventilations (< 12.5 mL) compared with the NeoNatalie. Although the test sequences with low compliance lung settings showed no difference in the percentage of excessive ventilations (> 37.5 mL) between the Upright and NeoNatalie, the test sequences with normal-compliance lung settings showed a higher percentage of excessive ventilations with both, and the increase was greater with the Upright than with the NeoNatalie (85.92% vs 71.39%, P < .001). The subjective acceptability and disassembly/reassembly tests were supportive of the new device design. CONCLUSIONS: The performance and acceptability of the Upright device in this user population suggest that the device may be suitable for effective ventilation by infrequent users in low-resource settings. The Upright device should be tested in such a setting. PMID- 26152469 TI - Inspiratory Capacity as an Indirect Measure of Immediate Effects of Positive Expiratory Pressure and CPAP Breathing on Functional Residual Capacity in Healthy Subjects. AB - BACKGROUND: Positive expiratory pressure (PEP) and CPAP are used to enhance breathing parameters such as functional residual capacity (FRC) in patients. Studies comparing effects of PEP and CPAP on FRC are few and variable. One reason for this may be that sophisticated equipment, not suitable in the clinical setting, is required. Because total lung capacity (TLC) consists of inspiratory capacity (IC) and FRC, a change in IC should result in a corresponding change in FRC given constant TLC. We aimed to evaluate the effects of different PEP and CPAP devices on IC as an indirect measure of induced changes in FRC from these devices in healthy subjects. METHODS: Twenty healthy subjects breathed with 2 PEP devices, a PEP mask (flow resistor) and a PEP bottle (threshold resistor), and 2 CPAP devices, a flow resistor and a threshold resistor, in a randomized order. The measurement sequence consisted of 30 breaths with an IC measurement performed before and immediately after the 30th breath while the subjects were still connected to the breathing device. Perceived exertion of the 30 breaths was measured with the Borg category ratio 10 scale. RESULTS: Three of the 4 breathing devices, the PEP mask and the 2 CPAP devices, significantly decreased IC (P < .001). Median perceived exertion was quite low for all 4 breathing devices, but the difference in perceived exertion among the different breathing devices was large. CONCLUSIONS: Provided that TLC is constant, we found that measurements of changes in IC could be used as an indirect measure of changes in FRC in healthy subjects. All investigated breathing devices except the PEP bottle decreased IC, as an indirect measure of increased FRC. PMID- 26152470 TI - Pressurized Metered-Dose Inhalers Versus Nebulizers in the Treatment of Mechanically Ventilated Subjects With Artificial Airways: An In Vitro Study. AB - BACKGROUND: The primary focus of previous aerosol research during mechanical ventilation was the endotracheal tube (ETT). Consequently, there are limited data in the literature on the delivery of inhaled medications administered with different aerosol devices in mechanically ventilated patients with a tracheostomy tube (TT). The purpose of this study was to quantify and compare the efficiency of aerosol devices in a lung model of an intubated and mechanically ventilated adult with a TT. METHODS: An in vitro lung model was constructed to simulate a ventilator-dependent adult with a Portex TT and a Mallinckrodt ETT (8-mm inner diameter). Aerosol was collected distal to the bronchi of an adult mannikin on a filter attached to a passive test lung. A ventilator delivered adult breathing parameters (tidal volume 450 mL, breathing frequency 20 breaths/min, peak expiratory flow 40 L/min, and inspiratory-expiratory ratio 1:3) to the airway. A jet nebulizer and pressurized metered-dose inhaler (pMDI) were placed in the inspiratory limb of the circuit 15 cm from the Y-adapter. The jet nebulizer was operated at 8 L/min to deliver albuterol sulfate (2.5 mg/3 mL), whereas an albuterol pMDI was actuated 4 times with a spacer. Drug was eluted from the filter and analyzed by spectrophotometry. RESULTS: Drug delivered via a TT was marginally greater compared with an ETT using the jet nebulizer and pMDI (P = .10 and .046, respectively). Although delivery efficiency with the pMDI was 3-fold greater than with the jet nebulizer with both a TT and an ETT (P = .001 and .002, respectively), the jet nebulizer delivered greater drug mass compared with the pMDI with either a TT (P = .01) or an ETT (P = .005). CONCLUSIONS: Aerosol drug delivery via a TT was greater than with an ETT, whereas the delivery efficiency of a pMDI via either airway was greater than that of a jet nebulizer. PMID- 26152471 TI - Factors Associated With Quality of Life in Subjects With Stable COPD. AB - BACKGROUND: The purpose of this study was to assess the impact of bronchiectasis, anxiety and depression, and parameters of disease severity on health-related quality of life (HRQOL) in subjects with COPD. METHODS: Sixty-two subjects with stable COPD were selected for the study. The presence of bronchiectasis in all subjects with COPD was investigated by high-resolution computed tomography. Pulmonary function tests were performed. Dyspnea was assessed using the Modified Medical Research Council (MMRC) dyspnea scale. Psychological disorders were investigated using the Hospital Anxiety and Depression Scale (HADS), and the HRQOL was examined using the St George Respiratory Questionnaire (SGRQ). RESULTS: High-resolution computed tomography revealed that 44 of 62 (70.9%) subjects with COPD had bronchiectasis. There were no differences in pulmonary function tests, symptoms, activities, impact, SGRQ total scores, and HADS scores between COPD subjects with and without bronchiectasis. Pearson correlation analyses showed that there was no significant association between the presence of bronchiectasis, bronchial wall thickness, or severity of bronchial dilatation and all subscales of the SGRQ or HADS scores. Additionally, HADS scores showed significant positive association with all subscales of the SGRQ in all subjects. In linear regression analysis, a statistically significant relationship was found between the SGRQ total score and percent-of-predicted FEV1, percent-of-predicted diffusing capacity of the lung for carbon monoxide, MMRC score, and anxiety score, but the SGRQ total score was not associated with age, body mass index, total number of hospitalizations, PaO2 , or depression score. CONCLUSIONS: The presence of bronchiectasis in subjects with COPD does not impact HRQOL and psychological disorders. However, disease severity, dyspnea levels, and anxiety scores predict poor HRQOL. PMID- 26152472 TI - Comparison of Proportional Assist Ventilation Plus, T-Tube Ventilation, and Pressure Support Ventilation as Spontaneous Breathing Trials for Extubation: A Randomized Study. AB - BACKGROUND: Failure to wean can prolong ICU stay, increase complications associated with mechanical ventilation, and increase morbidity and mortality. The spontaneous breathing trial (SBT) is one method used to assess weaning. The aim of this study was to assess proportional assist ventilation plus (PAV+) as an SBT by comparing its applicability, safety, and efficacy with T-tube and pressure support ventilation (PSV). METHODS: A randomized study was performed involving 160 adult subjects who remained on mechanical ventilation for > 24 h. Subjects were randomly assigned to the PAV+, PSV, or T-tube group. When subjects were ready to perform the SBT, subjects in the PAV+ group were ventilated in PAV+ mode (receiving support of up to 40%), the pressure support was reduced to 7 cm H2O in the PSV group, and subjects in the T-tube group were connected to one T-piece with supplemental oxygen. Subjects were observed for signs of intolerance, whereupon the trial was interrupted. When the trial succeeded, the subjects were extubated and assessed until discharge. RESULTS: The subjects were predominantly male (66.5%), and the leading cause of admission was traumatic brain injury. The groups were similar with respect to baseline characteristics, and no significant difference was observed among the groups regarding extubation success or failure. Analysis of the specificity and sensitivity revealed good sensitivity for all groups; however, the PAV+ group had higher specificity (66.6%) and higher sensitivity (97.6%), with prediction of ~ 92.1% of the success and failure events. CONCLUSIONS: No significant differences in the groups was observed regarding the rate of extubation failure, duration of mechanical ventilation, and ICU and hospital stay, indicating that PAV+ is an alternative for use as an SBT. PMID- 26152473 TI - Precautionary Practices of Respiratory Therapists and Other Health-Care Practitioners Who Administer Aerosolized Medications. AB - BACKGROUND: Respiratory therapists (RTs) and other health-care workers are potentially exposed to a variety of aerosolized medications. The National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers describes current exposure control practices and barriers to using personal protective equipment during administration of selected aerosolized medications. METHODS: An anonymous, multi-module, web-based survey was conducted among members of health-care professional practice organizations representing RTs, nurses, and other health-care practitioners. A module on aerosolized medications included submodules for antibiotics (amikacin, colistin, and tobramycin), pentamidine, and ribavirin. RESULTS: The submodules on antibiotics, pentamidine, and ribavirin were completed by 321, 227, and 50 respondents, respectively, most of whom were RTs. The relatively low number of ribavirin respondents precluded meaningful interpretation of these data and may reflect the rare use of this drug. Consequently, analysis focused on pentamidine, classified by NIOSH as a hazardous drug, and the antibiotics amikacin, colistin, and tobramycin, which currently lack authoritative safe handling guidelines. Respondents who administered pentamidine were more likely to adhere to good work practices compared with those who administered the antibiotics. Examples included training received on safe handling procedures (75% vs 52%), availability of employer standard procedures (82% vs 55%), use of aerosol delivery devices equipped with an expiratory filter (96% vs 53%) or negative-pressure rooms (61% vs 20%), and always using respiratory protection (51% vs 13%). CONCLUSIONS: Despite the availability of safe handling guidelines for pentamidine, implementation was not universal, placing workers, co-workers, and even family members at risk of exposure. Although the antibiotics included in this study lack authoritative safe handling guidelines, prudence dictates that appropriate exposure controls be used to minimize exposure to the antibiotics and other aerosolized medications. Employers and employees share responsibility for ensuring that precautionary measures are taken to keep exposures to all aerosolized medications as low as practicable. PMID- 26152474 TI - Impact of a Dedicated Noninvasive Ventilation Team on Intubation and Mortality Rates in Severe COPD Exacerbations. AB - BACKGROUND: Compared with usual care, noninvasive ventilation (NIV) lowers the risk of intubation and death for subjects with respiratory failure secondary to COPD exacerbations, but whether administration of NIV by a specialized, dedicated team improves its efficiency remains uncertain. Our aim was to test whether a dedicated team of respiratory therapists applying all acute NIV treatments would reduce the risk of intubation or death for subjects with COPD admitted for respiratory failure. METHODS: We carried out a retrospective study comparing subjects with COPD admitted to the ICU before (2001-2003) and after (2010-2012) the creation of a dedicated NIV team in a regional acute care hospital. The primary outcome was the risk of intubation or death. The secondary outcomes were the individual components of the primary outcome and ICU/hospital stay. RESULTS: A total of 126 subjects were included: 53 in the first cohort and 73 in the second. There was no significant difference in the demographic characteristics and severity of respiratory failure. Fifteen subjects (28.3%) died or had to undergo tracheal intubation in the first cohort, and only 10 subjects (13.7%) in the second cohort (odds ratio 0.40, 95% CI 0.16-0.99, P = .04). In-hospital mortality (15.1% vs 4.1%, P = .03) and median stay (ICU: 3.1 vs 1.9 d, P = .04; hospital: 11.5 vs 9.6 d, P = .04) were significantly lower in the second cohort, and a trend for a lower intubation risk was observed (20.8% vs 11% P = .13). CONCLUSIONS: The delivery of NIV by a dedicated team was associated with a lower risk of death or intubation in subjects with respiratory failure secondary to COPD exacerbations. Therefore, the implementation of a team administering all NIV treatments on a 24-h basis should be considered in institutions admitting subjects with COPD exacerbations. PMID- 26152480 TI - European Adder bites in dogs in southern Germany. A retrospective study over a 6.5-year period. AB - OBJECTIVE: In some regions of Germany dogs are presented to the veterinarian due to a snake bite, especially during the summer. These patients often show multiple clinical and laboratory deviations. Without a significant history diagnosis is commonly difficult. Aim of this retrospective study was to analyze exposure, physical examination and clinical pathology results as well as course and outcome in dogs presented after European adder bites. MATERIAL AND METHODS: Patient history of 15 dogs diagnosed with European adder bites over a 6.5-year-period were evaluated retrospectively. Normality of data distribution was tested by D'Agostino and Pearson omnibus normality test. Data were analyzed by T-test and Wilcoxon-matched-pairs-signed rank-test. P-values < 0.05 were considered significant. RESULTS: All 15 dogs were presented within 1-48 hours after the snakebite. Most common clinical signs were local swelling and pain. Clinical pathology results on day 1 included haemoconcentration, leukocytosis and coagulopathy. On the second day of hospitalization heart rate and haematocrit declined significantly. Treatment included fluid therapy, antibiotic and antihistaminic drugs, glucocorticosteroids, antivenom and analgesics. One of 15 dogs died on the third day of hospitalization, all others were discharged. Duration of hospitalization was between 1 and 8 days (mean 4.2 +/- 1.9 days). CLINICAL RELEVANCE: Dogs affected by European adder bites most often present with swelling and pain at the site of the bite, most frequently on the head and limbs. Patients require intensive symptomatic therapy including antibiotics and analgesics, if indicated. With adequate therapy survival rate is high. For some patients European adder bites may be lethal. PMID- 26152482 TI - Looking forward to looking back. PMID- 26152483 TI - Assessing the use of cognitive load measures in medical education. PMID- 26152484 TI - What if the 'trust' in entrustable were a social judgement? PMID- 26152485 TI - Training tomorrow's physician-advocates. PMID- 26152486 TI - When I say ... distributed cognition. PMID- 26152487 TI - When I say ... mentoring. PMID- 26152488 TI - A fresh perspective on medical education: the lens of the arts. AB - OBJECTIVES: This literature review was designed to examine the role of the arts in medical education. It is distinctive from previous literature reviews in that it focuses specifically on what medical education as a discipline can learn from the arts and does not seek to measure the effectiveness of arts-based educational interventions in students or clinicians. METHODS: A literature search using the terms 'educat*' or 'medic*' and phrases such as 'arts', 'therapy', 'medicine', 'arts therapy', 'professional artistry' and 'nursing/doctoral education' was conducted. The 60 items identified were filtered for relevance. Key data were extracted from the remaining items and subjected to a literature analysis to identify important or recurring themes. RESULTS: A total of 39 pieces of literature were included in the study. Collectively, these outlined four main areas in which the use of the arts impacts upon medical education. These refer to using the arts: (i) as a tool for professional development; (ii) to develop pedagogy; (iii) to critique the prevailing approach of medical education, and (iv) to view practice as a succession of performances. CONCLUSIONS: The effectiveness of the arts cannot be measured by yardsticks that have been set for judging technical proficiency or short-term impact. The possible outcomes of embracing the arts in medical education include an enriched view of lifelong learning and professional development, the potential to critique prevailing approaches to medical practice, and the revisualisation of medicine as a succession of performances. These open up the broader social aspects of medical practice to scrutiny and offer new and distinctive ways of exploring professional knowledge and identity. PMID- 26152489 TI - Why physicians teach: giving back by paying it forward. AB - CONTEXT: Despite the pace and intensity of the in-patient clinical setting, physicians carve out time for teaching medical students and residents. OBJECTIVES: The goal of this study was to explore what it means for physicians to teach students and residents in the in-patient setting. METHODS: We conducted semi-structured interviews with 15 practising physicians from the departments of internal medicine, surgery and paediatrics in three university teaching hospitals at McGill University, using an interpretive phenomenological methodology. RESULTS: Five themes elucidated the meaning of teaching for physicians in the in patient setting: (i) teaching was perceived as an integral part of their identity; (ii) teaching allowed them to repay former teachers for their own training; (iii) teaching gave them an opportunity to contribute to the development of the next generation of physicians; (iv) teaching enabled them to learn, and (v) teaching was experienced as personally energising and gratifying. Participants were morally and socially motivated to give time and effort through teaching (e.g. to pay forward their own privilege and thereby help to develop the next generation); teaching also gave them a sense of personal fulfilment (e.g. by allowing them to mould young minds and leave a legacy). CONCLUSIONS: This study holds a number of implications for medical education with relevance to the recruitment and retention of clinical teachers, recognition of clinical teaching, and evidence-informed faculty development. The findings also suggest that teaching in an academic setting can bring joy and fulfilment to practising physicians. PMID- 26152490 TI - How clinical supervisors develop trust in their trainees: a qualitative study. AB - CONTEXT: Clinical supervisors oversee trainees' performance while granting them increasing opportunities to work independently. Although the factors contributing to supervisors' trust in their trainees to conduct clinical work have been identified, how the development of trust is shaped by these factors remains less clear. OBJECTIVES: This study was designed to determine how supervisors develop and experience trust in resident (postgraduate years 2 and 3) trainees in the clinical workplace. METHODS: Internal medicine in-patient supervisors at two institutions were interviewed about the meaning and experience of developing trust in resident trainees. Transcribed data were coded and analysed using a phenomenographic approach. RESULTS: Forty-three supervisors participated. Supervisors characterised the meaning of trust from the perspectives of trainee competence and leadership or from their own perspective of needing to provide more or less supervision. Supervisors initially considered trust to be usually independent of prior knowledge of the resident, and then used sources of information about trust to develop their judgements of trust. Sources, which incorporated inference, included supervisors' comparisons with a standard, direct observation of the trainee as a team leader or care provider, and stakeholder input from team members, patients and families. Barriers against and accelerators to trust formation related to the resident, supervisor, resident-supervisor relationship, context and task. Trust formation had implications for supervisors' roles, residents' increasingly independent provision of care, and team functioning. CONCLUSIONS: From a general starting point, supervisors develop trust in residents informed by observation, inference and information gathered from the team and patients. Judgements of trust yield outcomes defined by supervisors' changing roles, the increasingly independent provision of care by residents, and team functioning. The implications of these findings for graded resident autonomy aligned with learning needs can inform the design of training environments to enable readiness for unsupervised practice. PMID- 26152491 TI - Not just 'for' but 'with': health advocacy as a partnership process. AB - CONTEXT: Health advocacy is often framed as an activity that physicians do for others. A physician uses her expertise to identify and address the health needs of patients or communities on their behalves. As part of a larger study, we uncovered data to suggest that effective health advocates work not just for but often with others to understand and address their health needs. OBJECTIVES: This paper explores and elaborates the important distinction between advocating with and for others. METHODS: We interviewed 10 physicians, identified by others as successful health advocates, about their advocacy activities. Informed by constructivist grounded theory, we gathered and evaluated data iteratively, continually revising the interview outline and concurrently refining our evolving themes. Once it had stabilised, the coding scheme was applied to the full set of transcripts. RESULTS: Health advocacy was framed by participants as an activity that was more often done with others, than for others. This manifested in two ways: (i) joining other voices: rather than always feeling a need to plan and act alone, our participants often described making efforts to find and join existing initiatives and to work collaboratively, and (ii) amplifying other voices: rather than authoritatively determining needs and enacting solutions on behalf of others, our participants often described making efforts to empower others to find their own voices, thereby fostering autonomy rather than reliance. Participants described factors and mechanisms that enabled them to approach advocacy in this manner. CONCLUSIONS: Successful health advocates often enact health advocacy with others, rather than exclusively for them. This partnership-based facilitative approach enables them to better appreciate the needs of those requiring support, and to ask: 'How can I help?' If this approach were more effectively reflected in formal constructions of the process, health advocacy might not only be practised more effectively, but might also be perceived as more achievable by trainees and physicians. PMID- 26152492 TI - Limitations of subjective cognitive load measures in simulation-based procedural training. AB - CONTEXT: The effective implementation of cognitive load theory (CLT) to optimise the instructional design of simulation-based training requires sensitive and reliable measures of cognitive load. This mixed-methods study assessed relationships between commonly used measures of total cognitive load and the extent to which these measures reflected participants' experiences of cognitive load in simulation-based procedural skills training. METHODS: Two groups of medical residents (n = 38) completed three questionnaires after participating in simulation-based procedural skills training sessions: the Paas Cognitive Load Scale; the NASA Task Load Index (TLX), and a cognitive load component (CLC) questionnaire we developed to assess total cognitive load as the sum of intrinsic load (how complex the task is), extraneous load (how the task is presented) and germane load (how the learner processes the task for learning). We calculated Pearson's correlation coefficients to assess agreement among these instruments. Group interviews explored residents' perceptions about how the simulation sessions contributed to their total cognitive load. Interviews were audio recorded, transcribed and subjected to qualitative content analysis. RESULTS: Total cognitive load scores differed significantly according to the instrument used to assess them. In particular, there was poor agreement between the Paas Scale and the TLX. Quantitative and qualitative findings supported intrinsic cognitive load as synonymous with mental effort (Paas Scale), mental demand (TLX) and task difficulty and complexity (CLC questionnaire). Additional qualitative themes relating to extraneous and germane cognitive loads were not reflected in any of the questionnaires. CONCLUSIONS: The Paas Scale, TLX and CLC questionnaire appear to be interchangeable as measures of intrinsic cognitive load, but not of total cognitive load. A more complete understanding of the sources of extraneous and germane cognitive loads in simulation-based training contexts is necessary to determine how best to measure and assess their effects on learning and performance outcomes. PMID- 26152493 TI - Measuring cognitive load: performance, mental effort and simulation task complexity. AB - CONTEXT: Interest in applying cognitive load theory in health care simulation is growing. This line of inquiry requires measures that are sensitive to changes in cognitive load arising from different instructional designs. Recently, mental effort ratings and secondary task performance have shown promise as measures of cognitive load in health care simulation. OBJECTIVES: We investigate the sensitivity of these measures to predicted differences in intrinsic load arising from variations in task complexity and learner expertise during simulation-based surgical skills training. METHODS: We randomly assigned 28 novice medical students to simulation training on a simple or complex surgical knot-tying task. Participants completed 13 practice trials, interspersed with computer-based video instruction. On trials 1, 5, 9 and 13, knot-tying performance was assessed using time and movement efficiency measures, and cognitive load was assessed using subjective rating of mental effort (SRME) and simple reaction time (SRT) on a vibrotactile stimulus-monitoring secondary task. RESULTS: Significant improvements in knot-tying performance (F(1.04,24.95) = 41.1, p < 0.001 for movements; F(1.04,25.90) = 49.9, p < 0.001 for time) and reduced cognitive load (F(2.3,58.5) = 57.7, p < 0.001 for SRME; F(1.8,47.3) = 10.5, p < 0.001 for SRT) were observed in both groups during training. The simple-task group demonstrated superior knot tying (F(1,24) = 5.2, p = 0.031 for movements; F(1,24) = 6.5, p = 0.017 for time) and a faster decline in SRME over the first five trials (F(1,26) = 6.45, p = 0.017) compared with their peers. Although SRT followed a similar pattern, group differences were not statistically significant. CONCLUSIONS: Both secondary task performance and mental effort ratings are sensitive to changes in intrinsic load among novices engaged in simulation-based learning. These measures can be used to track cognitive load during skills training. Mental effort ratings are also sensitive to small differences in intrinsic load arising from variations in the physical complexity of a simulation task. The complementary nature of these subjective and objective measures suggests their combined use is advantageous in simulation instructional design research. PMID- 26152494 TI - Enhancing international medical graduates' communication: the contribution of applied linguistics. AB - CONTEXT: International medical graduates (IMGs) make up one-third of the Australian medical workforce. Those from non-English-language backgrounds can face cultural and communication barriers, yet linguistic support is variable and medical educators are often required to provide feedback on both medical and communication issues. However, some communication difficulties may be very specific to the experiences of IMGs as second language users. OBJECTIVES: This interdisciplinary study combines perspectives from applied linguistics experts and clinical educators to address IMGs' difficulties from multiple dimensions and to enhance feedback quality. METHODS: Five video-recorded patient encounters with five IMGs were collected at Launceston General Hospital. Three clinical educators gave quantitative and qualitative feedback using the Rating Instrument for Clinical Consulting Skills, and two applied linguistics experts analysed the data for language, pragmatic and communication difficulties. The comparison of the educators' language-related feedback with linguistic analyses of the same interactions facilitated the exploration of differences in the difficulties identified by the two expert groups. RESULTS: Although the clinical educators were able to use their tacit intuitive understanding of communication issues to identify IMG difficulties, they less frequently addressed the underlying issues or suggested specific remedies in their feedback. CONCLUSIONS: This pilot study illustrates the effectiveness of interdisciplinary collaboration in highlighting the specific discourse features contributing to IMG communication difficulties and thus assists educators in deconstructing their intuitive knowledge. The authors suggest that linguistic insights can therefore improve communications training by assisting educators to provide more targeted feedback. PMID- 26152495 TI - Accuracy of self-monitoring during learning of radiograph interpretation. AB - CONTEXT: Despite calls for the improvement of self-assessment as a basis for self directed learning, instructional designs that include reflection in practice are uncommon. Using data from a screen-based simulation for learning radiograph interpretation, we present validity evidence for a simple self-monitoring measure and examine how it can complement skill assessment. METHODS: Medical students learning ankle radiograph interpretation were given an online learning set of 50 cases which they were asked to classify as 'abnormal' (fractured) or 'normal' and to indicate the degree to which they felt certain about their response (Definitely or Probably). They received immediate feedback on each case. All students subsequently completed two 20-case post-tests: an immediate post-test (IPT), and a delayed post-test (DPT) administered 2 weeks later. We determined the degree to which certainty (Definitely versus Probably) correlated with accuracy of interpretation and how this relationship changed between the tests. RESULTS: Of 988 students approached, 115 completed both tests. Mean +/- SD accuracy scores decreased from 59 +/- 17% at the IPT to 53 +/- 16% at the DPT (95% confidence interval [CI] for the difference: -2% to -10%). Mean self assessed certainty did not decrease (rates of Definitely: IPT, 17.6%; DPT, 19.5%; 95% CI for difference: +7.2% to -3.4%). Regression modelling showed that accuracy was positively associated with choosing Definitely over Probably (odds ratio [OR] 1.63, 95% CI 1.27-2.09) and indicated a statistically significant interaction between test timing and certainty (OR 0.72, 95% CI 0.52-0.99); thus, the accuracy of self-monitoring decayed over the retention interval, leaving students relatively overconfident in their abilities. CONCLUSIONS: This study shows that, in medical students learning radiograph interpretation, the development of self monitoring skills can be measured and should not be assumed to necessarily vary in the same way as the underlying clinical skill. PMID- 26152496 TI - Power and conflict in health care: everyone's responsibility. PMID- 26152497 TI - Hypercoagulable state evaluated by thromboelastography in patients with idiopathic membranous nephropathy. AB - The aims of this study were to evaluate the characteristics of hypercoagulable states in patients with membranous nephropathy (MN) via thromboelastography (TEG) and to identify risk factors. 235 MN patients who had undergone TEG examinations from 2011 to 2014 were included. An abnormality in at least two TEG parameters is considered a hypercoagulable state. Patient data was compared between the hypercoagulable and non-hypercoagulable groups. Potential risk factors for hypercoagulability were analyzed by logistic regression models. Subgroup analysis was performed in hypercoagulable patients. Compared to the non-hypercoagulable MN patients, the hypercoagulable patients showed a significantly higher proportion of female patients, urinary protein, platelet count, triglyceride and fibrinogen level, along with more severe hypoproteinemia and a reduction of serum antithrombin III. Correlation analysis showed that hypoproteinemia was the primary risk factor for hypercoagulability in MN patients. Among the hypercoagulable MN patients, a subgroup TEG parameter analysis showed that glucocorticoids-used subgroup and smoker subgroup had shortened time to initial fibrin formation (R value) and increased coagulation index respectively (P < 0.05), indicating a more serious hypercoagulable state. Meanwhile, the time to initial fibrin formation (R value) and time to clot formation (K value) of the statin-used patients were remarkably higher than those of the non-statin patients. TEG examinations facilitated the detection of hypercoagulable states in MN patients, and hypoproteinemia was the most important risk factor for hypercoagulability in these patients. The use of glucocorticoids and smoking may help to aggravate hypercoagulable states, while statin drugs may alleviate hypercoagulability. PMID- 26152498 TI - Lessons from the proteomic study of osteoarthritis. AB - Osteoarthritis is the most common rheumatic pathology and one of the leading causes of disability worldwide. It is a very complex disease whose etiopathogenesis is not fully understood. Furthermore, there are serious limitations for its management, since it lacks specific and sensitive biomarkers for early diagnosis, prognosis and therapeutic monitoring. Proteomic approaches performed in the last few decades have contributed to the knowledge on the molecular mechanisms that participate in this pathology and they have also led to interesting panels of putative biomarker candidates. In the next few years, further efforts should be made for translating these findings into the clinical routines. It is expected that targeted proteomics strategies will be highly valuable for the verification and qualification of biomarkers of osteoarthritis. PMID- 26152499 TI - [Radiological diagnostics of pediatric lungs]. AB - Pediatric lung diseases are a common clinical problem. Besides the clinical examination and laboratory tests, imaging studies are the mainstay in the diagnostics of pediatric lung diseases. Thorough consideration of radiation protection based on optimized equipment also includes the protection of relatives and medical staff. The high impact of radiation protection in children necessitates a different choice of imaging modalities compared to adults. Ultrasound and magnetic resonance imaging (MRI) as adjunct or complementary imaging methods are of greater value than computed tomography (CT). The suspicion of pneumonia is the most common reason for chest imaging examinations in children. An anteroposterior or posteroanterior view chest X-ray is sufficient in most cases and sometimes in combination with ultrasound. The latter can also be used alone for follow-up examinations if the clinical presentation does not change. Additionally, ultrasound is applied to examine unclear structures seen on chest X-rays, such as the thymus or pulmonary sequestration in adjunct with color coded duplex sonography. A chest X-ray is also the method of choice to examine the various forms of respiratory distress syndrome, such as wet lung disease or surfactant deficiency syndrome in newborns. Fluoroscopy is used in older children with suspected ingestion and/or aspiration of foreign bodies and CT is mostly used for staging and follow-up of thoracic and pulmonary structures in pediatric oncology. Recent technical advances, e.g. iterative reconstruction, have dramatically reduced the CT dosage. Apart from some indications (e.g. tumors and sequestration) MRI is rarely used in children; however, its potential for functional analyses (e.g. perfusion and ventilation) may increase the application in the near future. PMID- 26152500 TI - Abbreviated screening protocol for breast MRI: a feasibility study. AB - RATIONALE AND OBJECTIVES: To compare the performance of two shortened breast magnetic resonance imaging (MRI) protocols to a standard MRI protocol for breast cancer screening. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act compliant, institutional review board-approved pilot study, three fellowship-trained breast imagers evaluated 48 breast MRIs (24 normal, 12 benign, and 12 malignant) selected from a high-risk screening population. MRIs were presented in three viewing protocols, and a final Breast Imaging-Reporting and Data System assessment was recorded for each case. The first shortened protocol (abbreviated 1) included only fat-saturated precontrast T2-weighted, precontrast T1-weighted, and first pass T1-weighted postcontrast sequences. The second shortened protocol (abbreviated 2) included the abbreviated 1 protocol plus the second pass T1-weighted postcontrast sequence. The third protocol (full), reviewed after a 1-month waiting period, included a nonfat-saturated T1 weighted sequence, fat-saturated T2-weighted, precontrast T1-weighted, and three or four dynamic postcontrast sequences. Interpretation times were recorded for the abbreviated 1 and full protocols. Sensitivity and specificity were compared via a chi-squared analysis. This pilot study was designed to detect a 10% difference in sensitivity with a power of 0.8. RESULTS: There was no significant difference in sensitivity between the abbreviated 1 (86%; P = .22) or abbreviated 2 (89%; P = .38) protocols and the full protocol (95%). There was no significant difference in specificity between the abbreviated 1 (52%; P = 1) or abbreviated 2 (45%; P = .34) protocols and the full protocol (52%). The abbreviated 1 and full protocol interpretation times were similar (2.98 vs. 3.56 minutes). CONCLUSIONS: In this pilot study, reader performance comparing two shortened breast MRI protocols to a standard protocol in a screening cohort were similar, suggesting that a shortened breast MRI protocol may be clinically useful, warranting further investigation. PMID- 26152501 TI - 3 Tesla (23)Na magnetic resonance imaging during aerobic and anaerobic exercise. AB - RATIONALE AND OBJECTIVES: The aim of the work described here was to determine the feasibility of monitoring Na(+) concentration and distribution in muscle/skin during aerobic/anaerobic exercise with (23)Na magnetic resonance imaging (MRI). MATERIALS AND METHODS: The Na(+) concentration and water content of muscle/skin of the left lower leg of six healthy subjects (mean age, 26 years; range, 22-30 years; three men and three women) were assessed before and after aerobic/anaerobic cycle ergometry and during recovery with 3-T (23)Na/(1)H MRI. (23)Na MRI was performed with a custom-made knee coil. A gradient echo sequence with an acquisition time of 3.25 minutes, echo time of 2.07 ms, repetition time of 100 ms, and spatial resolution of 3 * 3 * 30 mm(3) was applied. Phantoms with increasing sodium concentration served for quantification via linear extrapolation. Blood values were determined by blood gas analysis. RESULTS: The concentration of Na(+) significantly increased during anaerobic exercise in all muscle compartments except the medial gastrocnemius muscle, whereas no significant change was observed in most muscle compartments during aerobic exercise (only the soleus muscle exhibited a significant increase in Na(+) concentration during aerobic exercise: 1.6 +/- 1.5 mmol/kg, 4.5%, P = .046). During anaerobic exercise, the mean Na(+) concentration of the triceps surae and the whole leg increased by 9.0% (3.1 +/- 2.1 mmol/kg, P = .016) and 6.5% (2.2 +/- 1.3 mmol/kg, P < .01). MRI revealed a water-independent increase in Na(+) concentration in most muscle compartments during anaerobic exercise. Na(+) concentration significantly decreased during recovery after anaerobic and aerobic exercise in all muscle compartments except the soleus. The Na(+) concentration of the skin did not significantly change during anaerobic/aerobic exercise. CONCLUSIONS: Sodium(23) MRI allows reliable and noninvasive visualization and quantification of Na(+) concentration and distribution in muscle and skin during exercise. (23)Na MRI can be used to gain new insights into Na(+) homeostasis, presumably leading to better comprehension of pathophysiology. PMID- 26152502 TI - Three amino acid residues of an odorant-binding protein are involved in binding odours in Loxostege sticticalis L. AB - Odorant-binding proteins (OBPs) play an important role in insect olfactory processes and are thought to be responsible for the transport of pheromones and other semiochemicals across the sensillum lymph to the olfactory receptors within the antennal sensilla. As an important general odorant binding protein in the process of olfactory recognition, LstiGOBP1 of Loxostege sticticalis L. has been shown to have good affinity to various plant volatiles. However, the binding specificity of LstiGOBP1 should be further explored in order to better understand the olfactory recognition mechanism of L. sticticalis. In this study, real-time PCR experiments indicated that LstiGOBP1 was expressed primarily in adult antennae. Homology modelling and molecular docking were then conducted on the interactions between LstiGOBP1 and 1-heptanol to understand the interactions between LstiGOBP1 and their ligands. Hydrogen bonds formed by amino acid residues might be crucial for the ligand-binding specificity on molecular docking, a hypothesis that was tested by site-directed mutagenesis. As predicted binding sites for LstiGOBP1, Thr15, Trp43 and Val14 were replaced by alanine to determine the changes in binding affinity. Finally, fluorescence assays revealed that the mutants Thr15 and Trp43 had significantly decreased binding affinity to most odours; in mutants that had two-site mutations, the binding to the six odours that were tested was completely abolished. This result indicates that Thr15 and Trp43 were involved in binding these compounds, possibly by forming multiple hydrogen bonds with the functional groups of the ligands. These results provide new insights into the detailed chemistry of odours' interactions with proteins. PMID- 26152503 TI - The myocardial and coronary histopathology and pathogenesis of hypoplastic left heart syndrome. AB - Hypoplastic left heart syndrome has the greatest mortality rate among all CHDs and without palliation is uniformly fatal. Despite noble efforts, the aetiology of this syndrome is unknown and a cure remains elusive. The genetic and anatomic heterogeneity of hypoplastic left heart syndrome supports a rethinking of old hypotheses and warrants further investigation into the histological and vascular variations recognised with this syndrome. In an effort to elucidate the pathogenesis of hypoplastic left heart syndrome, this review will focus on its unique myocardial and coronary pathology as well as evaluate the association of hypoplastic left heart syndrome with the endocardial fibroelastosis reaction. PMID- 26152505 TI - Surgical Options in the Problematic Arteriovenous Haemodialysis Access. AB - The aim of the paper is to review surgical options in problematic arteriovenous haemodialysis access--in particular, to explore and discuss some surgical alternatives to interventional radiology in the case of failing, failed or complicated arteriovenous access. There is copious evidence to support endovascular techniques to treat non-maturation, stenosis, thrombosis and other complications of arteriovenous access. However, there may be times when the surgery-first approach might be a useful adjunct, alternative or even preferable, including the creation or revision of an anastomosis in the forearm, which may yield better patency rates than endovascular intervention. The creation and maintenance of haemodialysis access can be a complex process and the surgeon and the interventional radiologist should work closely together. The distinct roles of the surgeon and the interventional radiologist in the treatment of a problematic arteriovenous access remain debatable and the authors suggest a multidisciplinary team approach when planning treatment of access complications, which may require repeated interventions. PMID- 26152504 TI - Laryngomalacia and swallowing function in children. AB - OBJECTIVES/HYPOTHESIS: 1) To determine the prevalence of dysphagia in children with laryngomalacia, 2) To ascertain whether severity of laryngomalacia influences the presence of swallowing dysfunction, and 3) To examine whether patients with medical comorbidities and laryngomalacia have a higher prevalence of swallowing dysfunction. STUDY DESIGN: Retrospective cohort study. METHODS: All patients seen in the aerodigestive center at our institution between January 2007 and December 2012 with the diagnosis of laryngomalacia were included. Swallowing function was assessed by symptoms, clinical swallowing evaluations (CSE) performed by speech pathologists, modified barium swallow (MBS) studies, and fiberoptic endoscopic evaluations of swallowing (FEES). RESULTS: There were 324 patients with laryngomalacia identified (41.4% female, 58.6% male). Severity of laryngomalacia was categorized in 279 patients, with 62.7% mild, 28.7% moderate, and 8.6% severe. Gastroesophageal reflux disease (GERD) was diagnosed in 69.8% of patients. Other medical comorbidities included Down syndrome (3.1%), neurological impairment (6.5%), and congenital heart disease (0.9%). Symptoms of dysphagia or feeding difficulty were present in 163/324 (50.3%), and failure to thrive was present in 31/324 patients (9.6%). At least one abnormal swallowing assessment was present in 97/120 (80.8%) patients presenting with subjective dysphagia and 43/65 (66.2%) patients without subjective dysphagia. A total of 140/185 (75.7%) patients had at least one abnormal baseline swallowing assessment. There was no significant relationship between severity of laryngomalacia and presence of abnormal swallowing function based on symptoms, CSE, MBS, or FEES. However, patients with greater severity were more likely to have failure to thrive. There was not a significant association between the presence of swallowing dysfunction or disease severity and medical comorbidities such as Down syndrome, neurological impairment, or congenital heart disease. However, GERD was more likely to be present in patients with moderate and severe laryngomalacia than in patients with mild disease. CONCLUSIONS: Swallowing dysfunction is common in children with laryngomalacia regardless of disease severity or other medical comorbidities. Swallowing studies are frequently abnormal in laryngomalacia patients presenting both with and without subjective symptoms of dysphagia. Dysphagia assessment should be considered as part of the evaluation of infants with laryngomalacia. LEVEL OF EVIDENCE: 4. PMID- 26152506 TI - Erratum to: In Vivo Proof of Superselective Transarterial Chemoembolization with 40-MUm Drug-Eluting Beads in a Patient with Hepatocellular Carcinoma. PMID- 26152507 TI - High Residual Collagen-Induced Platelet Reactivity Predicts Development of Restenosis in the Superficial Femoral Artery After Percutaneous Transluminal Angioplasty in Claudicant Patients. AB - PURPOSE: Although platelet reactivity is routinely inhibited with aspirin after percutaneous angioplasty (PTA) in peripheral arteries, the restenosis rate in the superficial femoral artery (SFA) is high. Interaction of activated platelets and the endothelium in the region of intervention could be one reason for this as collagen in the subendothelium activates platelets. MATERIALS AND METHODS: A prospective study evaluating on-site platelet reactivity during PTA and its influence on the development of restenosis with a total of 30 patients scheduled for PTA of the SFA. Arterial blood was taken from the PTA site after SFA; platelet function was evaluated with light transmission aggregometry. After 3, 6, 12, and 24 months, duplex sonography was performed and the restenosis rate evaluated. RESULTS: Eight out of 30 patients developed a hemodynamically relevant restenosis (>50 % lumen narrowing) in the PTA region during the 24-month follow up period. High residual collagen-induced platelet reactivity defined as AUC >30 was a significant predictor for the development of restenosis [adjusted odds ratio 11.8 (9.4, 14.2); P = .04]. CONCLUSIONS: High residual collagen-induced platelet reactivity at the interventional site predicts development of restenosis after PTA of the SFA. Platelet function testing may be useful for identifying patients at risk. PMID- 26152508 TI - Climate change and soil salinity: The case of coastal Bangladesh. AB - This paper estimates location-specific soil salinity in coastal Bangladesh for 2050. The analysis was conducted in two stages: First, changes in soil salinity for the period 2001-2009 were assessed using information recorded at 41 soil monitoring stations by the Soil Research Development Institute. Using these data, a spatial econometric model was estimated linking soil salinity with the salinity of nearby rivers, land elevation, temperature, and rainfall. Second, future soil salinity for 69 coastal sub-districts was projected from climate-induced changes in river salinity and projections of rainfall and temperature based on time trends for 20 Bangladesh Meteorological Department weather stations in the coastal region. The findings indicate that climate change poses a major soil salinization risk in coastal Bangladesh. Across 41 monitoring stations, the annual median projected change in soil salinity is 39 % by 2050. Above the median, 25 % of all stations have projected changes of 51 % or higher. PMID- 26152509 TI - Decreased expression of vitamin D receptor may contribute to the hyperimmune status of patients with acquired aplastic anemia. AB - Acquired aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2 D3 ], the biologically active metabolite of vitamin D, is a critical modulator of immune response via binding with vitamin D receptor (VDR). Previous studies have established that 1,25(OH)2 D3 and VDR were involved in the pathogenesis of some autoimmune diseases. In this study, we evaluated the involvement of 1,25(OH)2 D3 and VDR on T-cell responses in AA. Plasma 25(OH)D3 levels were comparable between patients with AA and healthy controls. Surprisingly, VDR mRNA was significantly lower in untreated patients with AA than in healthy controls. Subsequent in vitro experiments revealed that 1,25(OH)2 D3 treatment suppressed the proliferation of lymphocytes and inhibited the secretion of interferon-gamma, tumor necrosis factor-alpha, and interleukin 17A, meanwhile promoting the production of transforming growth factor-beta1 in patients with AA. Moreover, 1,25(OH)2 D3 inhibited the differentiation of type 1 and Th17 cells but induced the differentiation of type 2 and regulatory T cells. Interestingly, VDR mRNA was elevated in healthy controls after 1,25(OH)2 D3 treatment, but not in patients with AA. In conclusion, decreased expression of VDR might contribute to the hyperimmune status of AA and appropriate vitamin D supplementation could partly correct the immune dysfunction by strengthening signal transduction through VDR in patients with AA. PMID- 26152510 TI - The in vitro and in vivo performance of a strontium-containing coating on the low modulus Ti35Nb2Ta3Zr alloy formed by micro-arc oxidation. AB - The beta-titanium alloy is thought to be a promising alloy using as orthopedic or dental implants owing to its characteristics, which contains low elastic modulus, high corrosion resistance and well biocompatibility. Our previous study has reported that a new beta-titanium alloy Ti35Nb2Ta3Zr showed low modulus close to human bone, equal tissue compatibility to a traditional implant alloy Ti6Al4V. In this study, micro-arc oxidation (MAO) was applied on the Ti35Nb2Ta3Zr alloy to enhance its surface characteristics and biocompatibility and osseointegration ability. Two different coatings were formed, TiO2 doped with calcium-phosphate coating (Ca-P) and calcium-phosphate-strontium coating (Ca-P-Sr). Then we evaluated the effects of the MAO coatings on the Ti35Nb2Ta3Zr alloy through in vitro and in vivo tests. As to the characteristics of the coatings, the morphology, chemical composition, surface roughness and contact angle of MAO coatings were tested by scanning electron microscopy, energy dispersive spectroscopy, atomic force microscopy, and video contact-angle measurement system respectively. Besides, we performed MTT assay, ALP test and cell morphology adhesion test on materials to evaluate the MAOed coating materials' biocompatibility in vitro. The in vivo experiment was performed through rabbit model. Alloys were implanted into rabbits' femur shafts, then we performed micro CT, histological and sequential fluorescent labeling analysis to evaluate implants' osseointegration ability in vivo. Finally, the Ca-P specimens and Ca-P Sr specimens exhibited a significant enhancement in surface roughness, hydrophilicity, cell proliferation, cell adhesion. More new bone was found around the Ca-P-Sr coated alloy than Ca-P coated alloy and Ti35Nb2Ta3Zr alloy. In conclusion, the MAO treatment improved in vitro and in vivo performance of Ti35Nb2Ta3Zr alloy. The Ca-P-Sr coating may be a promising modified surface formed by MAO for the novel beta-titanium alloy Ti35Nb2Ta3Zr. PMID- 26152511 TI - Technique to optimize magnetic response of gelatin coated magnetic nanoparticles. AB - The paper describes the results of optimization of magnetic response for highly stable bio-functionalize magnetic nanoparticles dispersion. Concentration of gelatin during in situ co-precipitation synthesis was varied from 8, 23 and 48 mg/mL to optimize magnetic properties. This variation results in a change in crystallite size from 10.3 to 7.8 +/- 0.1 nm. TEM measurement of G3 sample shows highly crystalline spherical nanoparticles with a mean diameter of 7.2 +/- 0.2 nm and diameter distribution (sigma) of 0.27. FTIR spectra shows a shift of 22 cm( 1) at C=O stretching with absence of N-H stretching confirming the chemical binding of gelatin on magnetic nanoparticles. The concept of lone pair electron of the amide group explains the mechanism of binding. TGA shows 32.8-25.2% weight loss at 350 degrees C temperature substantiating decomposition of chemically bind gelatin. The magnetic response shows that for 8 mg/mL concentration of gelatin, the initial susceptibility and saturation magnetization is the maximum. The cytotoxicity of G3 sample was assessed in Normal Rat Kidney Epithelial Cells (NRK Line) by MTT assay. Results show an increase in viability for all concentrations, the indicative probability of a stimulating action of these particles in the nontoxic range. This shows the potential of this technique for biological applications as the coated particles are (i) superparamagnetic (ii) highly stable in physiological media (iii) possibility of attaching other drug with free functional group of gelatin and (iv) non-toxic. PMID- 26152512 TI - Enhanced cell-wall damage mediated, antibacterial activity of core-shell ZnO@Ag heterojunction nanorods against Staphylococcus aureus and Pseudomonas aeruginosa. AB - Hybrid ZnO@Ag core-shell nanorods have been synthesized by a synthetic strategy based on seed mediated growth. Formation of core-shell nanostructures was confirmed by UV- diffused reflectance spectroscopy (UV-DRS), X-ray diffraction studies, field emission scanning electron microscopy and high resolution transmission electron microscopy. UV-DRS analysis of hybrid core-shell nanorods suggests the possibility of interfacial electron transfer between surface anchored Ag nanoclusters and ZnO nanorods. Successful decoration of Ag nanoclusters with an average diameter of ~7 +/- 0.5 nm was observed forming the heterojunctions on the surface of the ZnO nanorods. An enhanced antibacterial property was observed for the ZnO@Ag core-shell nanorods against both Staphylococcus aureus and Pseudomonas aeruginosa lbacteria. The synergetic antibacterial activity of ZnO@Ag nanorods was found to be more prominent against Gram-positive bacteria than Gram-negative bacteria. The plausible reason for this enhanced antibacterial activity of the core-shell nanorods can be attributed to the physical damage caused by the interaction of the material with outer cell wall layer due to the production of reactive oxygen species by interfacial electron transfer between ZnO nanorods and plasmonic Ag nanoclusters. Overall, the ZnO@Ag core-shell nanorods were found to be promising materials that could be developed further as an effective antibacterial agent against wide range of microorganisms to control spreading and persistence of bacterial infections. PMID- 26152514 TI - Phloroglucinol Protects INS-1 Pancreatic beta-cells Against Glucotoxicity-Induced Apoptosis. AB - Decreasing numbers, and impaired function, of pancreatic beta-cells are key factors in the development of type 2 diabetes. This study was designed to investigate whether phloroglucinol protected pancreatic beta-cells against glucotoxicity-induced apoptosis using a rat insulinoma cell line (INS-1). High glucose treatment (30 mM) induced INS-1 cell death; however, the level of glucose induced apoptosis was significantly reduced in cells treated with 100-MUM phloroglucinol. Treatment with 10-100-MUM phloroglucinol increased cell viability and decreased intracellular levels of reactive oxygen species, nitric oxide, and lipid peroxidation dose-dependently in INS-1 cells pretreated with high glucose. Furthermore, phloroglucinol treatment markedly reduced the protein expression of Bax, cytochrome c, and caspase 9, while increasing anti-apoptotic Bcl-2 protein expression. Cell death type was examined using annexin V/propidium iodide staining, revealing that phloroglucinol markedly reduced high glucose-induced apoptosis. These results demonstrated that phloroglucinol could be useful as a potential therapeutic agent for the protection of pancreatic beta-cells against glucose-induced apoptosis. PMID- 26152513 TI - Evolution and conservation of JmjC domain proteins in the green lineage. AB - Histone modification regulates plant development events by epigenetically silencing or activating gene expression, and histone methylation is regulated by histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs). The JmjC domain proteins, an important KDM family, erase methyl marks (CH3-) from histones and play key roles in maintaining homeostasis of histone methylation in vivo. Here, we analyzed 169 JmjC domain proteins from whole genomes of plants ranging from green alga to higher plants together with 36 from two animals (fruit fly and human). The plant JmjC domain proteins were divided into seven groups. Group-I KDM4/JHDM3 and Group-V JMJD6 were found in all the plant species and the other groups were detected mainly in vascular or seed plants. Group-I KDM4/JHDM3 was potentially associated with demethylation of H3K9me2/3, H3K27me2/3, and H3K36me1/2/3, Group-II KDM5A with H3K4me1/2/3, Group-III KDM5B with H3K4me1/2/3 and H3K9me1/2/3, Group-V JMJD6 with H3R2, H4R3, and hydroxylation of H4, and Group-VII KDM3/JHDM2 with H3K9me1/2/3. Group-IV/Group-VI JmjC domain-only A/B proteins were involved in hydroxylation and demethylation of unknown substrate sites. The binding sites for the cofactors Fe(II) and alpha-ketoglutarate in the JmjC domains also were analyzed. In the alpha-ketoglutarate binding sites, Thr/Phe/Ser and Lys were conserved and in the Fe(II) binding sites, two His and Glu/Asp were conserved. The results show that JmjC domain proteins are a conserved family in which domain organization and cofactor binding sites have been modified in some species. Our results provide insights into KDM evolution and lay a foundation for functional characterization of KDMs. PMID- 26152515 TI - Palliative balloon pulmonary valvuloplasty for infants with unrestrictive ventricular septal defect or single ventricle associated with severe pulmonary stenosis. AB - BACKGROUND: Symptomatic infants with unrestrictive ventricular septal defect (VSD) or single ventricle with severe pulmonary stenosis (PS) are typically treated surgically. High surgical risk infants may benefit from catheter-based palliative pulmonary valvuloplasty. METHODS: We retrospectively reviewed all patients with severe PS associated with unrestrictive VSD or single ventricle who underwent palliative pulmonary valvuloplasty as initial management and describe outcomes. RESULTS: From 2000 to 2013, 16 patients met inclusion criteria and underwent valvuloplasty at a median age and weight of 25 (range 1-352) days and 3.65 (range 2.2-12) kg. Common diagnoses included tetralogy of Fallot (50%) and double-outlet right ventricle (25%). In all, the indication was cyanosis. Reasons to defer surgery included low weight (37.5%), preference for complex operation at older age (31.25%) and significant comorbidity (18.75%). Following valvuloplasty, significant increases in oxygen saturation (83.1+/-8.8 vs. 74.7+/-8.7%, P=0.008) and QP:QS (1.6+/-0.5 vs. 0.8+/-0.3, P=0.0005) occurred. All two ventricle patients (n=10) ultimately had complete operative repair at a median of 125 (range 27-382) days after valvuloplasty, during which time there was 20.3+/-9.2 g/day of weight gain without change in oxygen saturation. Single ventricle patients who underwent cavopulmonary connection (n=3) had similar weight gain and palliation time, but with a decrease in oxygen saturation. Two patients required reintervention to augment QP prior to definitive repair. CONCLUSIONS: In select infants with unrestrictive VSD or single ventricle associated with severe PS, palliative pulmonary valvuloplasty provides an effective and durable method of increasing oxygen saturation until definitive surgical treatment can be performed. PMID- 26152516 TI - Thorny Laurels: the Impostor Phenomenon in Academic Psychiatry. PMID- 26152517 TI - RalB regulates contractility-driven cancer dissemination upon TGFbeta stimulation via the RhoGEF GEF-H1. AB - RalA and RalB proteins are key mediators of oncogenic Ras signaling in human oncogenesis. Herein we investigated the mechanistic contribution of Ral proteins to invasion of lung cancer A549 cells after induction of epithelial-mesenchymal transition (EMT) with TGFbeta. We show that TGFbeta-induced EMT promotes dissemination of A549 cells in a 2/3D assay, independently of proteolysis, by activating the Rho/ROCK pathway which generates actomyosin-dependent contractility forces that actively remodel the extracellular matrix, as assessed by Traction Force microscopy. RalB, but not RalA, is required for matrix deformation and cell dissemination acting via the RhoGEF GEF-H1, which associates with the Exocyst complex, a major Ral effector. Indeed, uncoupling of the Exocyst subunit Sec5 from GEF-H1 impairs RhoA activation, generation of traction forces and cell dissemination. These results provide a novel molecular mechanism underlying the control of cell invasion by RalB via a cross-talk with the Rho pathway. PMID- 26152518 TI - Global trade will accelerate plant invasions in emerging economies under climate change. AB - Trade plays a key role in the spread of alien species and has arguably contributed to the recent enormous acceleration of biological invasions, thus homogenizing biotas worldwide. Combining data on 60-year trends of bilateral trade, as well as on biodiversity and climate, we modeled the global spread of plant species among 147 countries. The model results were compared with a recently compiled unique global data set on numbers of naturalized alien vascular plant species representing the most comprehensive collection of naturalized plant distributions currently available. The model identifies major source regions, introduction routes, and hot spots of plant invasions that agree well with observed naturalized plant numbers. In contrast to common knowledge, we show that the 'imperialist dogma,' stating that Europe has been a net exporter of naturalized plants since colonial times, does not hold for the past 60 years, when more naturalized plants were being imported to than exported from Europe. Our results highlight that the current distribution of naturalized plants is best predicted by socioeconomic activities 20 years ago. We took advantage of the observed time lag and used trade developments until recent times to predict naturalized plant trajectories for the next two decades. This shows that particularly strong increases in naturalized plant numbers are expected in the next 20 years for emerging economies in megadiverse regions. The interaction with predicted future climate change will increase invasions in northern temperate countries and reduce them in tropical and (sub)tropical regions, yet not by enough to cancel out the trade-related increase. PMID- 26152519 TI - SMS text pre-notification and delivery of reminder e-mails to increase response rates to postal questionnaires in the SUSPEND trial: a factorial design, randomised controlled trial. AB - BACKGROUND: Patient-reported outcomes are vital in informing randomised controlled trials (RCTs) and health-care interventions and policies from the patient's perspective. However, participant non-response may introduce bias and can affect the generalisability of the trial. This study evaluates two interventions aimed at increasing response rates to postal questionnaires within a large, UK-wide RCT: pre-notification via short messenger service (SMS) text prior to sending the initial mailing of trial questionnaires versus no pre notification; for non-responders to the initial mailing of the questionnaires, an e-mail reminder (containing a hyperlink to complete the questionnaire online) versus a postal reminder. METHODS: This study is a 2 * 2 partial factorial design RCT nested within an RCT of medical expulsive therapy for ureteric stone disease. Participants who supplied a mobile telephone number were randomly assigned to receive an SMS text pre-notification of questionnaire delivery or no pre notification. Those who supplied an e-mail address were randomly assigned to receive a questionnaire reminder by e-mail or post. Participants could be randomly assigned to the pre-notification comparison or the reminder comparison or both. The primary outcome measure was response rate at each questionnaire time point. RESULTS: Four hundred eighteen participants were randomly assigned to the SMS pre-notification comparison (80% were male, and the mean age was 41 years with a standard deviation (SD) of 11.1). The intervention had no effect on response rate at either questionnaire time point. In subgroup analyses, SMS pre notification increased response rates in women but only at the first questionnaire time point. One hundred nineteen participants were randomly assigned to the reminder comparison (80% were male, and the mean age was 42 years with an SD of 12.1). There was no difference in response rate in those who received an e-mail reminder compared with those who received a postal reminder. CONCLUSIONS: SMS text pre-notification of questionnaire delivery and email delivery of questionnaire reminders did not improve response rates. There was some evidence to suggest that SMS text pre-notification may be effective in women, and further studies to investigate this may be warranted. E-mail reminders for participants to return their postal questionnaire could be advantageous given that response rates were similar following either type of reminder and the low cost of delivering an e-mail compared with a postal reminder. This is a substudy of the SUSPEND trial (ISCTRN69423238) (18 Nov. 2010). PMID- 26152520 TI - Upregulation of miR-372 and -373 associates with lymph node metastasis and poor prognosis of oral carcinomas. AB - OBJECTIVES/HYPOTHESIS: Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and survival in OSCC has not improved significantly in the last few decades. MicroRNAs (miRNAs) have an important regulatory role in human cancer, including oral carcinogenesis. MiR-372 and miR-373 perform oncogenic and tumor suppressive functions of between different human malignancies. This study investigated the miR-372 and miR-373 expression and their clinical implication in OSCC. METHODS: Fifty patients with primary OSCC were included in the study. Primary cancer cells and matched normal oral epithelium were purified by laser capture microdissection. RNA were extracted from these samples. The expression levels of miR-372 and miR-373 in the tissue of OSCC patients were measured by quantitative reverse transcription polymerase chain reaction. The large tumor suppressor kinase 2 (LATS2) protein expression level was measured by Western blotting. RESULTS: Both miR-372 and miR-373 was up-regulated in OSCC tissue relative to control mucosa. Among different clinical variables, over-expression of miR-372 and miR-373 were associated with nodal metastasis, lymphovascular invasion, and poor survival. Multivariate analysis showed that both high miR-372 and miR-373 expression were independent predictors for poor survival in OSCC. MiR 372 regulated LATS2 expression in OSCC cell lines. LATS2 expression levels are inversely correlated miR-372 in OSCC tissues. CONCLUSION: Over-expression of miR 372 and miR-373 indicate worse survival in OSCC. LEVEL OF EVIDENCE: N/A. PMID- 26152521 TI - Carnosic acid inhibits STAT3 signaling and induces apoptosis through generation of ROS in human colon cancer HCT116 cells. AB - Carnosic acid (CA), the main antioxidant compound of Rosmarinus officinalis L., has been reported to possess anticancer activity. However, the molecular mechanisms underlying the anticancer effects of CA remain poorly understood. Our study revealed that CA treatment significantly reduced the viability of human colon cancer HCT116, SW480, and HT-29 cells. Treatment with CA induced apoptosis, which was associated with the induction of p53 and Bax, inhibition of Mdm2, Bcl 2, and Bcl-xl expression, activation of caspase-9, and -3, and the cleavage of PARP in HCT116 cells. CA inhibited the constitutive phosphorylation, the DNA binding and the reporter gene activity of STAT3 in HCT116 cells by blocking the phosphorylation of upstream JAK2 and Src kinases. Moreover, CA attenuated the expression of STAT3 target gene products, such as survivin, cyclin D1, D2, and D3. In STAT3-overexpressed HCT116 cells, CA inhibited cell viability and the expression of cyclin D1 and survivin. Furthermore, CA treatment induced the generation of ROS in these colon cancer cells. Pretreatment of cells with ROS scavenger N-acetyl cysteine abrogated the inhibitory effect of CA on the JAK2 STAT3/Src-STAT3 signaling and rescued cells from CA-induced apoptosis by blocking the induction of p53 and the cleavage of caspase-3 and PARP in HCT116 cells. However, L-buthionine-sulfoximine, a pharmacological inhibitor of GSH synthesis, increased CA-induced ROS production, thereby potentiating apoptotic effect of CA. In conclusion, our study provides the first report that CA induced apoptosis in HCT116 cells via generation of ROS, induction of p53, activation of caspases, and inhibition of STAT3 signaling pathway. (c) 2015 Wiley Periodicals, Inc. PMID- 26152523 TI - The negative consequences of consequential validity. PMID- 26152522 TI - The effect of TISSEEL fibrin sealant on seroma formation following complex abdominal wall hernia repair: a single institutional review and derived cost analysis. AB - PURPOSE: The authors evaluated the ability of a fibrin sealant (TISSEELTM: Baxter Healthcare Corp, Deerfield, IL, USA) to reduce the incidence of post-operative seroma following abdominal wall hernia repair. METHODS: We performed a 4-year retrospective review of patients undergoing abdominal wall hernia repair, with and without TISSEEL, by a single surgeon (FEE) at The Johns Hopkins Hospital. Demographics, surgical risk factors, operative data and 30-day outcomes, including wound complications and related interventions, were compared. The quantity and cost of Tisseel per case was reviewed. RESULTS: A total of 250 patients were evaluated: 127 in the TISSEEL group and 123 in the non-TISSEEL control group. The average age for both groups was 56.6 years (P = 0.97). The majority of patients were female (TISSEEL 52.8%, non-TISSEEL 56.1%, P = 0.59) and ASA Class III (TISSEEL 56.7%, non-TISSEEL 58.5%, P = 0.40). There was no difference in the average defect size for both groups (TISSEEL 217 +/- 187.6 cm(2), non-TISSEEL 161.3 +/- 141.5 cm(2), P = 0.36). Surgical site occurrences occurred in 18.1% of the TISSEEL and 13% of the non-TISSEEL group (P = 0.27). There was a trend towards an increased incidence of seroma in the TISSEEL group (TISSEEL 11%, non-TISSEEL 4.9%, P = 0.07). A total of $124,472.50 was spent on TISSEEL, at an average cost of $995.78 per case. CONCLUSIONS: In the largest study to date, TISSEELTM application offered no advantage for the reduction of post-operative seroma formation following complex abdominal hernia repair. Moreover, the use of this sealant was associated with significant costs. PMID- 26152524 TI - FhCaBP2: a Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains. AB - FhCaBP2 is a Fasciola hepatica protein which belongs to a family of helminth calcium-binding proteins which combine an N-terminal domain containing two EF hand motifs and a C-terminal dynein light chain-like (DLC-like) domain. Its predicted structure showed two globular domains joined by a flexible linker. Recombinant FhCaBP2 interacted reversibly with calcium and manganese ions, but not with magnesium, barium, strontium, copper (II), colbalt (II), iron (II), nickel, lead or potassium ions. Cadmium (II) ions appeared to bind non-site specifically and destabilize the protein. Interaction with either calcium or magnesium ions results in a conformational change in which the protein's surface becomes more hydrophobic. The EF-hand domain alone was able to interact with calcium and manganese ions; the DLC-like domain was not. Alteration of a residue (Asp-58 to Ala) in the second EF-hand motif in this domain abolished ion-binding activity. This suggests that the second EF-hand is the one responsible for ion binding. FhCaBP2 homodimerizes and the extent of dimerization was not affected by calcium ions or by the aspartate to alanine substitution in the second EF-hand. The isolated EF-hand and DLC-like domains are both capable of homodimerization. FhCaBP2 interacted with the calmodulin antagonists trifluoperazine, chlorpromazine, thiamylal and W7. Interestingly, while chlorpromazine and thiamylal interacted with the EF-hand domain (as expected), trifluoperazine and W7 bound to the DLC-like domain. Overall, FhCaBP2 has distinct biochemical properties compared with other members of this protein family from Fasciola hepatica, a fact which supports the hypothesis that these proteins have different physiological roles. PMID- 26152525 TI - Palladium-Catalyzed Synthesis of alpha-Diimines from Triarylbismuthines and Isocyanides. AB - In this study, we report a highly selective coupling reaction between triarylbismuthines and isocyanides using palladium diacetate as the catalyst, affording alpha-diimines, with the formation of three C-C bonds. Among several aryl sources (Ar-YLn: Y = B, Sn, Pb, Sb, Bi, I), only triarylbismuthines successfully undergo coupling with isocyanides to selectively afford alpha diimines. The coupling reaction exhibits the advantages of high atom economy and convenient operation, with no need for any additive. PMID- 26152526 TI - Validation of a liquid chromatography-high-resolution mass spectrometry method for the analysis of ceftiofur in poultry muscle, kidneys and plasma: A unique accuracy profile for each and every matrix. AB - A robust, selective and specific liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed for the quantification of total residues of ceftiofur, an antibiotic belonging to the 3rd generation cephalosporins in plasma, muscle and kidney of poultry. Ceftiofur and conjugates in samples were firstly hydrolyzed with dithioerythritol into desfuroylceftiofur, which was then stabilized by derivatization with iodoacetamide into desfuroylceftiofur acetamide. Sample were then submitted to a solid phase extraction followed the accurate mass analysis of desfuroylceftiofur acetamide by LC-HRMS in full scan mode using a linear trap quadrupole (LTQ)-Orbitrap mass spectrometer with a resolving power 60,000 full width at half maximum (FWHM). The method was fully validated over a dosing range between 100 and 2000 MUg kg(-1) (or MUg L(-1)) using the total error approach. Accuracy profiles a graphical decision-making tool were built by computing results of validation procedure with acceptance limits set at +/-60%, and beta-expectation tolerance intervals, i.e. the interval assuming to contain a beta % of future measurements (beta=90% in this study). Total measurement error including trueness, repeatability and intermediate precision were evaluated. Relative bias of trueness was never exceeding the threshold of 6% in all matrices at all level of concentration. The mean relative standard deviation for repeatability was lower than 16% at all levels of concentration for all matrices; the mean relative standard deviation for intermediate precision was lower than 25% at all levels of concentration for all matrices. This validation approach proved that the method is reliable for the quantification in each and every matrix (i.e. plasma, kidneys and muscle of chicken) thanks to only one single regression model (i.e. linear) obtained from external calibration standards (without matrix) with deuterated labelled internal standard. The developed method was applied during a depletion study of ceftiofur in chicken tissues and plasma. PMID- 26152527 TI - Preparation of a biomimetic polyphosphorylcholine monolithic column for immobilized artificial membrane chromatography. AB - The present work aims to prepare a novel phosphatidylcholine functionalized monolithic stationary phase by in situ co-polymerization of 12-methacryloyl dodecylphosphocholine (MDPC) and ethylene dimethacrylate (EDMA) for immobilized artificial membrane chromatography. Scanning electron microscopy, energy dispersive X-ray spectroscopy, FT-IR spectroscopy, pore size distribution analysis, zeta-potential analysis and micro-HPLC were used to evaluate the monolithic structure and physicochemical properties. Satisfactory morphology, high mechanical stability, good permeability and chromatographic performance were obtained on the optimized monolithic columns. A typical reverse-phase retention mechanism was observed over a wide range of organic solvent content (acetonitrile< 80%). The optimized poly(MDPC-co-EDMA) monolith exhibited good selectivity for proteins and basic drugs. Good correlation was observed between the retention on commercial IAM column (IAM.PC.DD2) and poly(MDPC-co-EDMA) monolith. This novel poly(MDPC-co-EDMA) monolith exhibited good potential for studying the drug-membrane interaction. PMID- 26152528 TI - Generalized window factor analysis for selective analysis of the target component in real samples with complex matrices. AB - In chromatographic analysis of multicomponent real samples, peak overlapping, high level of noise and background are frequently encountered, making the qualitative and quantitative analysis difficult or even impossible. In this work, an algorithm named as generalized window factor analysis (GWFA) was proposed for quantitative analysis of the target components in the samples with complex matrices by gas chromatography-mass spectrometry (GC-MS). The theory and calculation of GWFA are just similar with the conventional window factor analysis (WFA), but the "window" is defined as the selected channels (mass-to-charge ratios) in the mass spectral dimension of the data matrix, instead of a continuous region in chromatographic dimension along the retention time. Therefore, the generalized window for a target component can be easily determined with the help of the mass spectrum. Then, the calculated mass spectrum can be obtained with the window and quantitative determination can be achieved with the help of the standard. Both simulated and experimental data were investigated with the proposed method. Whether or not a peak shift occurs during the test, accurate results were obtained from the overlapping GC-MS signals with high level of noise and background. PMID- 26152529 TI - Identification of extracellularly phosphorylated membrane proteins. AB - Ecto-protein kinases phosphorylate extracellular membrane proteins and exhibit similarities to casein kinases and protein kinases A and C. However, the identification of their protein substrates still remains a challenge because a clear separation from intracellular phosphoproteins is difficult. Here, we describe a straightforward method for the identification of extracellularly phosphorylated membrane proteins in human umbilical vein endothelial cells (HUVECs) and K562 cells which used the protease bromelain to selectively remove ectoproteins from intact cells and combined this with the subsequent analysis using IMAC and LC-MS/MS. A "false-positive" strategy in which cells without protease treatment served as controls was applied. Using this approach we identified novel phosphorylation sites on five ectophosphoproteins (NOTCH1, otopetrin 1, regulator of G-protein signalling 13 (RGS13), protein tyrosine phosphatase receptor type D isoform 3 (PTPRD), usherin isoform B (USH2A)). Use of bromelain appears to be a reliable technique for the further identification of phosphorylated surface-exposed peptides when extracellular adenosine-5' triphosphate is elevated during purinergic signalling. PMID- 26152531 TI - A test of phenotypic selection on petal form in the wild carnation, Dianthus inoxianus. AB - Floral phenotypes are considered a product of pollinator-mediated selection, which also has the side effect of decreasing floral variation within species. Correlates of flower visibility and function were studied in a carnation species (Dianthus inoxianus), which has crepuscular anthesis and scent-based pollination by the hawkmoth Hyles livornica. We also assessed constancy of flower form in nature and in cultivation and, using fruit set as an estimate of plant relative fitness, tested whether the main pollinator exerted phenotypic selection on floral traits. Petal claw, which is roughly equivalent to the average depth at which an insect's proboscis must be inserted to reach nectar, was remarkably constant among wild plants (coefficient of variation 8%). In contrast, the area of the visible part of the petal, and the intensity of a coloured dot pattern on the petal was very variable (respectively CV = 34% and 102%). Cultivation in a common environment revealed significant variation among genotypes as regards petal area, degree of laciniation and extension of the dot pattern, but not petal claw length, which remained steady. Petal area, shape and colour did not affect relative fitness during the year of study, but plants with intermediate petal claws (i.e. floral tubes) set significantly more fruit. Results are compatible with low response of the main pollinator to variation in visual traits (petal area, laciniation, colour) and high responsiveness to variation in other aspects (tube length). Inconsistent phenotypic selection by pollinators may add to other causes of floral variation in the genus Dianthus, the causes of which are discussed. PMID- 26152532 TI - Packaging gas selects lactic acid bacterial communities on raw pork. AB - AIMS: To study the effect of different CO2-rich packaging atmospheres on the composition of lactic acid bacterial communities proliferating on raw pork. METHODS AND RESULTS: Raw pork loin was inoculated with a mixture of 14 lactic acid bacteria (LAB) strains previously associated with meat and packaged with four gas atmospheres: (i) 100% CO2 (ii) 80% N2 20% CO2 (iii) 80% N2, 20% CO2, 0.4% CO and (iv) 80% O2, 20% CO2. The colony counts of LAB, pH and composition of packaging gas were monitored every other day during the storage of 14 days at +6 degrees C. The compositions of lactic acid bacterial communities on pork were evaluated after 7 days of storage with culture-independent, terminal restriction fragment length polymorphism analysis of 16S rRNA gene fragments. After 14 days of storage, the compositions of lactic acid bacterial communities were evaluated using identification of plate-grown LAB isolates by numerical ribopattern analysis. The results showed that (i) high concentration of CO2 in packaging atmosphere favoured Lactobacillus sp. (ii) high concentration of O2 favoured Leuconostoc spp. (iii) atmosphere with 80% N2, 20% CO2 favoured Lactococcus sp. CONCLUSIONS: The composition of modified packaging atmosphere is a major factor selecting lactic acid bacterial communities proliferating on raw meat. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides an explanation for the compositions of lactic bacterial communities on modified atmosphere packaged raw meat observed in other studies. The results should be considered when attempting to manipulate LAB communities in raw meat, e.g. by protective cultures. PMID- 26152533 TI - From the Editor in Chief. PMID- 26152534 TI - In memory of Professor Giuseppina Scassellati Sforzolini. PMID- 26152535 TI - In memory of Professor Giuseppina Scassellati Sforzolini. PMID- 26152536 TI - Primary DNA damage in welders occupationally exposed to extremely-low-frequency magnetic fields (ELF-MF). AB - BACKGROUND: Electric arc welding is known to involve considerable exposure to extremely-low-frequency magnetic fields (ELF-MF; 50 Hz). The aim of the present study was to evaluate individual exposure to ELF-MF during arc welding and to assess the eventually associated genotoxic hazard by evaluating primary DNA damage. METHODS: The study group comprised 21 electric arc welders (exposed) and 21 non-exposed control subjects (healthy blood donors). Occupational exposure to ELF-MF was measured using personal dosimeters worn during one complete work-shift (7 am to 5 pm). The extent of primary DNA damage was measured in peripheral blood leukocytes with the standard procedure of the alkaline comet assay. RESULTS: Tail length showed to have similar values in welders and controls. Whereas, the data showed a significant decrease for tail intensity (p = 0.01) and tail moment (p = 0.02) counts in exposed subjects compared to controls. CONCLUSIONS: The different results of our present study and published investigations from other research groups reporting positive results in the comet assay might be a result of different chromium and/or nickel (or other metals) exposure levels, which lead to DNA-protein cross-links at lower concentrations and DNA single-strand breakages at higher concentrations. Since these results are derived from a small-scale pilot study, a larger scale study should be undertaken. PMID- 26152537 TI - Compliance with guidelines on antibiotic prophylaxis in hip and knee arthroplasty in Italy: results of the GISIO-ISChIA project. AB - BACKGROUND: The Perioperative Antibiotic Prophylaxis (PAP) contributes considerably to the total amount of antibiotics used in hospitals and has been shown to be associated with increase in antibiotic resistance and healthcare costs. The level of compliance with the national guidelines of current practices of PAP for elective hip and knee prosthesis procedures in a network of Italian hospitals (the multicentre Surgical Site Infection surveillance project GISIO ISChIA), has been evaluated. METHODS: Compliance of the current prophylactic antibiotic practices with the published national guidelines was assessed for each included operative procedure, considering indication, timing of administration, prescribed antimicrobial agent and total duration of prophylaxis. RESULTS: A total of 14 hospitals and 1285 surgical procedures were included. 99.4% of patients received antimicrobial prophylaxis pre-operatively and 73.0% of patients received PAP within the recommended time period (within 60 minutes before incision). The rate of compliance with discontinuation of PAP within 24 hours after initiation of surgery was 70.2%. Taking into account all doses administered, the antibiotic was chosen appropriately in 57.7% of patients. PAP was performed appropriately, in accordance with national guidelines, in 43.6% of surgical operations. CONCLUSIONS: Given the increasing number of replacement procedures in Italy and in Europe, the gap between the evidence-based guidelines and practice must be appropriately addressed in order to improve PAP practices. PMID- 26152538 TI - Epidemiologic surveillance of mesothelioma in Umbria. AB - BACKGROUND: Malignant mesothelioma (MM) is becoming a prominent health issue due to its low survival and for its increasing incidence in various countries. The objectives of this study were to evaluate epidemiological characteristics and trends of MM in the Umbrian Region for the period 2003-2013. METHODS: All cases of MM reported to Umbrian Population Cancer Registry between 2003 and 2013. Incidence Annual Standardized Rates (ASRs) were analyzed for all histological types of MM. Estimated Annual Percent Change (APC) and joinpoint regression analysis were used to out light the time trend of MM. Geographical distribution of the relative risk for each municipality was calculated by Standardized Incidence Ratios SIRs. RESULTS: 191 (156 males) MM cases were recorded in Umbrian residents in the period 2003-2013. Pleural mesothelioma affected 92.1% of the total. Gender ratio M/F was 5.9:1. ASRs for MM was 3.2 among men and 0.6 among women. Joinpoint analysis showed a decrease in females APC -8.4 (95% IC -33.7 26.6) and an increase in males APC 5.8 (95% IC -0.9-13.0). An occupational exposure was identified in 43.7% of females and in 90.7% of males. CONCLUSIONS: The protracted cancer latency and the continued asbestos existence as environmental contaminant in existing buildings, as well as a carcinogenic risk for the workers involved in removing operations of material containing asbestos justifies the investment in a specific surveillance system. Also important would be to implement a national risk communication strategy addressed to the general population, environment surveillance of the high risk areas and guarantee that all workers involved that even may deal with asbestos are always fully equipped and trained, not only for their individual risk but also for the potential risk of non correct disposal. PMID- 26152539 TI - Regulations relating to mycotoxins in almonds in European context. AB - Mycotoxins are secondary metabolites produced by several species of fungi and having a toxic effect on humans and farm animals. In particular, almonds, a rich source of nutrients and phytochemicals, can be contaminated by aflatoxins, one of the most important mycotoxins, mainly produced by Aspergillus flavus and Aspergillus parasiticus. The reference regulations in this field are continuously improved and updated worldwide. This paper reports the current state of the European regulations on aflatoxins in almonds concerning the limits, and the procedures for performing official controls and for import. PMID- 26152540 TI - The care of pregnant women and their babies: empirical data from Umbria region. AB - BACKGROUND: The promotion of the concept of evidence-based health care in the field of maternity care began in the 1980s; the indicators in this field were devised to enable us to know key components of care for mothers and babies and to relate them to health outcomes. METHODS: The study is based on data from the Standard Certificate of Live Birth (SCLB) forms of the Umbria region (Italy) during 2012, which merges data from each mother and her baby for a total of 7964 records. We followed the healthcare indicators recommended by World Health Organization for monitoring and evaluating maternal and child health services. We considered number of prenatal medical visits and timing of first antenatal visit such as indicators of Antenal care, and mode of delivery and place of birth by volume of deliveries such as indicators of Intrapartum care in healthcare maternal and child services. Odds ratios were calculated to indicate the likelihood of some individual and social variables across appropriate access to prenatal care. RESULTS: It is present an association between social disadvantage (mothers' educational level and mothers' country of birth) and inappropriate access to prenatal care, low number of prenatal medical visits (below 4) and late timing of first visit (after more than 12 gestational weeks). In Umbria there are 11 place of birth, 9 of I level and 2 of II level. Overall, 29.3% births occurred in 6 maternity units with fewer than 500 births in 2012 (in Italy is 7.3%). The average rate of cesarean section observed in the NTSV sample (Nulliparous, Terminal, Single, Vertex), was 28.2%. This value was higher than expected, especially in this class with an indication for the physiological birth. The World Health Organization recommends that the caesarean section rate should not be higher than 10% to 15%. Moreover there is a wide variability between birth centers (7.2% -41.4%). CONCLUSIONS: The use of mother and child prenatal care services was associated with individual characteristics of the mothers from less advantage social classes (i.e., unemployed or poorly educated); cesarean section was higher than expected, especially in the NTSV sample; we foresee an important role for application of indicators that proactively help health-care professionals to deliver the right care at the right time. PMID- 26152541 TI - Prevention of healthcare-associated infections: knowledge among dental students in seven Italian universities. AB - BACKGROUND: Lack of knowledge is the major reason for non-compliance with correct healthcare-associated infections (HAI) prevention procedures. The aim of this study was to evaluate knowledge of the Dental School (DSS) and Dental Hygiene (DHS) students with regard to the prevention of HAI, as basic knowledge for improving and harmonizing the educational content in the different Italian Universities. METHODS: A cross-sectional study was carried out using an anonymous questionnaire that was completed by DSS (I, II, III, IV, and V year) in seven Universities and DHS (I, II, and III year) in three Universities. The questions dealt with three specific areas: healthcare-associated infections, standard precautions and hand hygiene. Factors associated with an unacceptable level of knowledge (score <17.5) were analyzed using a logistic regression model. A p value <0.05 was considered to be significant. RESULTS: Five hundred and four questionnaires were collected: 81.5% for DSS and 18.5% for DHS. Mean overall score (+/-DS) achieved by the total number of students was 18.2+/-2.93 on an overall perfect score of 25; 18.2+/-3.04 for DSS and 17.8+/-2.31 for DHS. Stratifying by area, the average score 2.7+/-1.07 (53%) for HAI, 10.3+/-1.61 (85.9%) for standard precautions, and 5.2+/-1.44 (64.8%) for hand hygiene was observed. A significantly different level of knowledge (p<0.001) between DSS and DHS was observed only for HAI (2.8+/-1.07 for DSS vs 2.1+/-0.96 for DHS). Significant differences among the academic years were found only for DSS concerning HAI and standard precautions. The logistic regression model showed that an age <23 years was a risk factor for lack of knowledge on HAI, but a protective factor for lack of knowledge about standard precautions and hand hygiene; attending DH degree course was associated with lack of knowledge on HAI. CONCLUSIONS: Although the overall score obtained both by DSS and DHS indicated an acceptable level of knowledge, lack of knowledge was highlighted, in particular, for hand hygiene. Therefore, it is necessary to implement and validate effective teaching models in undergraduate courses in order to provide the scientific basis and the theoretical and practical preparation for the prevention and control of HAI. PMID- 26152542 TI - Recording Non Communicable Chronic Diseases at Risk Behaviours in General Practice. A qualitative study using the PRECEDE-PROCEED Model. AB - OBJECTIVE: Full, accurate registration of behavioral risk factors in patients is essential for good quality preventive action in General Practice. In addition, the GP's records are useful for epidemiological surveillance of risk behavior and assessment of preventive actions in the community and also for the accurate Case Management in the Continuity of Care perspective. Up to date, very little research has been carried out in Italy in this area. METHODS: The PRECEDE-PROCEED model was used to analyze data of a semi-structured interview of purposively selected Italian GPs. PRECEDE, the diagnostic component of the model, was used to highlight factors that affected their recording of behavioral risk lifestyles. The PRECEDE framework distinguishes three categories of factors influencing behavior: Predisposing (wanting to do), Reinforcing Factors (rewards for doing) and Enabling Factors (being able to do) 2. RESULTS: The Predisposing Factors were identified as the GPs' positive attitude to writing up structured, systematic records of patient data and the low attitude towards registration of the behavioural risk factors with respect to clinical data. Enabling Factors were: the high load of paperwork; the requirement for quantitative registration of certain factors; the software information structure which limited recording of some risk behaviors. Reinforcing Factors were the GPs perception that patients were reluctant to providing data on their behavior and that they as GPs did not have enough incentives for this work; current local epidemiology selectively focused physicians' attention on recording behaviours related to prevalent diseases. CONCLUSIONS: It has been possible to identify ways to improve the quality of GPs records of behavioral risk factors in patients: 1)equipping computer systems with detection procedures to guide GP recordings : 2) training to improve the GP's awareness and attitude and 3) incentives that are not only financial but also linked to professional development. PMID- 26152543 TI - Antibiotic resistance as a major public health concern: epidemiology and economic impact. AB - Antimicrobial resistance (AMR) is mainly sustained by the improper use of antibiotics and has become a global public health concern both in the field of human and animal health. Italy has the highest prevalence of AMR among European countries, in particular carbapenem-resistant Klebsiella pneumoniae, which reached 34.3% in 2013. Multidrug-resistant microorganisms' infections are associated with increased risk of complications, higher hospitalization rates, increased healthcare costs, loss of productivity and increased mortality. This paper summarizes the most recent epidemiological data regarding the spread of antibiotic resistance in Italy, consumption and economic impact, outlining the need for timely action and integrated approaches in all countries. PMID- 26152544 TI - Maternal and Perinatal Health in Umbria region in 2012. AB - BACKGROUND: Pregnancy and childbirth still involve risk for pregnant women and their babies and health in the perinatal period remains an important public health priority. This study addresses the question of perinatal health in Umbria region. METHODS: Data were obtained from the administrative source of the regional Standard Certificate of Live Births in Umbria in 2012. We used population data, which merges data from each mother and her baby for a total of 7964 records. To describe perinatal health we considered pathological pregnancy, fetal growth defect, birth weight, gestational age, Apgar scores at 5 minutes and stillbirth such as indicators of Maternal and Neonatal Health in according with population characteristics and risk factors (maternal age, parity, mothers' educational level and mothers' country of birth). RESULTS: In Umbria, in 2012 we have: - 29 stillbirths corresponding to a rate of stillbirths of 3.52 0/00 (stillbirths per 1000 births) - a perinatal mortality rate ( stillbirths and deaths in the first week of life) of 4.9 per 1000 live births and stillbirths - an Infant mortality rate (within the first year of life) of 2.5 per 1000 live births The 1.4 % of infants underwent neonatal resuscitation. This percentage detects an indicative Apgar score of important neonatal suffering (0-3) in the 1% of neonates. The frequency of infants with birth weight less than 2500 grams (LBW) was 6.4 %, with higher values in females (7.3%) than males (2.7%). The frequency of infants with birth weight less than 1500 grams is 0.8%. The preterm birth (<37 weeks of gestation) rate is 6.3% of the total: 5.6% are pregnancies among the 32 and 36 weeks of gestation and 0.7% are pregnancies under the 32nd week of gestation. The pathological pregnancies are 7.9% and the Fetal Growth Restriction (FGR) is 2.7%. The health perinatal indicators considered were different in different population subgroups. The most representative population was Italian women (76.8%), with maternal age between 25-34 years (56.4%), primiparous (61.9%) and mothers with medium education levels (48.1%). CONCLUSIONS: Results highlight the existence of differences in perinatal health. Worse maternal condition and neonatal status were observed especially for less advantaged social classes (i.e., foreign or poorly educated). Such inequalities should be examined in all areas of public policy and public services, to ensure equal opportunity for all. PMID- 26152545 TI - Detection of Listeria monocytogenes in ready-to-eat foods sampled from a catering service in Apulia, Italy. AB - OBJECTIVE: Listeria monocytogenes is currently considered a relevant emerging food-borne pathogen. In particular, the European Centre for Disease Prevention and Control (ECDC) illustrates its widespread presence in different foods. In the present article, L. monocytogenes prevalence was estimated in cooked ready-to-eat foods sampled from a catering service in a Apulia city, southern Italy. METHODS: The study was carried out from January to June 2014 in according to Regulation (EC) No. 852/2004, and ISO 11290-1:1996/Amd.1:2004 methods. RESULTS: Listeria spp. was isolated in 8.3% of the samples: L. monocytogenes was identified with the highest prevalence in potato gateau (66.6%), followed by rice dishes (11.1%), Listeria innocua was isolated from potato purea (11.1%) and cooked vegetables (11.1%). CONCLUSIONS: These preliminary results confirm the diffusion of the microorganism in ready-to-eat products; therefore, strategies aimed at protecting the consumers should be adopted. First of all, correct hygiene procedures should be followed and then microbiological tests should be implemented in order to early detect Listeria spp. (not only LM) contamination in cooked foods. PMID- 26152546 TI - Effects of the "PreveDi" lifestyle modification trial on metabolic syndrome. AB - BACKGROUND: Metabolic syndrome (MetS) is a cluster of metabolic disorders that includes central obesity, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia and high blood pressure (BP). Statistical reports suggest that the prevalence of MetS has dramatically increased during the recent years and is considered a worldwide epidemic. MetS has been found to be associated with increased risk of all-cause mortality, cardiovascular diseases (CVD), type 2 diabetes mellitus, chronic kidney disease and some types of cancer. MetS has a high socioeconomic cost and it is therefore extremely important that MetS is prevented and treated by simple and feasible methods. METHODS: The PreveDi study is a pilot before/after preventive trial aimed at the evaluation of the impact of a brief lifestyle intervention on changes in metabolic syndrome (MetS) risk factors. Recruitment was carried out in two community (council-run) pharmacies in the province of Perugia, Italy and the sample population consisted of 186 adults aged 45 or more who volunteered to participate. At enrolment the participants received a booklet illustrating general recommendations for MetS. During the 6 months follow-up period, participants were invited (by brochures and text messaging on cellular phones) to attend five conferences, five cooking classes, and twelve physical activity sessions. The conferences and the kitchen course were aimed to disseminate a healthy diet strategy focused primarily on reducing glycemic and insulinemic response. At baseline and follow-up MetS parameters were evaluated using medical equipments available in community pharmacies. RESULTS: At baseline, MetS was observed approximately in 52.2% of the PreveDi population, the MetS prevalence decreased with a higher education level in women, but not in men. Attendance to intervention programs was low and there was no significant difference between physical activity recorded at baseline and at follow-up. A slightly increased adherence to the healthy diet recommendations was observed for males. Waist circumference, systolic and diastolic blood pressure, fasting glucose and triglycerides did not change significantly, whereas weight, BMI and total cholesterol did. At follow-up the prevalence of MetS decreased, though not significantly, only in women (from 54,1 to 45.2%). Moreover, in women the negative correlation with education level was lost. CONCLUSIONS: This pilot study, even if with some limitations, suggests that MetS can be prevented and/or treated by simple and sustainable methods. PMID- 26152547 TI - Effects of the dietary replacement of maize with sun-dried cocoa pods on the performance of growing rabbits. AB - Twenty seven mixed-breed growing rabbits (1.2-1.3 kg body weight) aged 10-12 weeks were used to study the effects of the dietary replacement of maize with sun dried cocoa pod husks on the performance of growing rabbits in a 6-week trial. Three treatment diets were compounded whereby sun-dried cocoa pod husks replaced maize at 0, 50, and 100 %, respectively. The animals were divided among the three treatment diets so that each diet had 3 replicates of 3 animals each. Feed intake and weight gain were recorded; faeces were also collected for digestibility trials, and cost analysis was also carried out. Results showed a significant difference (P < 0.05) in daily feed intake between the dietary treatments. However, there was no significant difference (P > 0.05) in the final metabolic weights, total metabolic weight gain, daily growth rate, and feed conversion ratio between the treatments. The digestibility study showed a decrease in the digestibility of dry matter and metabolisable energy with the increase in cocoa pod husk inclusion. Cost analysis indicate that significant net gains can be made by incorporating 200 g sundried cocoa pod husks per kg of the diet of growing rabbits compared with the same proportion of maize. These results suggest that sun-dried cocoa pod husks can totally replace maize and provide a cheap source of energy in the diets of growing rabbits. PMID- 26152548 TI - Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. AB - OBJECTIVE: To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies directed against other phospholipids (PLs), PL binding proteins, coagulation factors and a mechanistic test for resistance of Annexin A5 (AnxA5) anticoagulant activity in APS and control populations. METHODS: We searched PubMed and EMBASE using the key words APS, antiphospholipid antibodies, non-criteria, new assays, IgA anticardiolipin antibodies, lupus anticoagulant, anti-Domain I, IgA anti-beta2-glycoprotein I antibodies, antiphosphatidylserine, anti-phosphatidylethanolamine, anti-phosphatidic acid, antiprothrombin, antiphosphatidylserine-prothtombin, anti-vimentin/cardiolipin complex and Annexin A5 resistance. Studies that met inclusion criteria to describe prevalence of non criteria aPLs in APS patients (n > 10), disease and healthy control subjects were systematically examined. RESULTS: We selected 16 retrospective studies of 1404 APS patients, 1839 disease control and 797 healthy controls. The highest prevalence of non-criteria aPLs in the largest number of patients with APS was found in IgA anti-beta2GPI studies (129/229, 56.3%), AnxA5R (87/163, 53.4%) and IgG anti-Domain I (241/548, 44.0%). CONCLUSION: Our finding of a significantly high prevalence of all non-criteria aPLs studied in patients with APS compared with controls was tempered by wide variation in sample size, retrospective collection, assay methodology and different determination of positivity. Therefore, prospective studies of sufficient size and appropriate methodology are required to evaluate the significance of these assays and their utility in the management of patients with APS. PMID- 26152549 TI - Needle Thoracostomy for Patients with Prolonged Transport Times: A Case-control Study. AB - Introduction The use of prehospital needle thoracostomy (NT) is controversial. Some studies support its use; however, concerns exist regarding misplacement, inappropriate patient selection, and iatrogenic injury. Even less is known about its efficacy in situations where there is a delay to definitive care. Hypothesis/Aim To determine any differences in survival of patients who underwent NT in the setting of prolonged versus short transport times, and to describe differences in mechanisms and complications between the two groups. METHODS: This was a retrospective, matched, case-control study of trauma patients in a four county Emergency Medical Service (EMS) system from April 1, 2007 through April 1, 2013. This system serves an urban, rural, and wilderness catchment area. A prehospital database was queried for all patients in whom NT was performed, identifying 182 patients. When these calls were limited to those with prolonged transport times, the search was narrowed to 32 cases. A matched control group, based on age and gender, with short transport times was then created as a comparison. Data collected from prehospital and hospital records included: demographics; mechanism of injury; call status; response to NT; and final outcome. Univariate and multivariate analyses were conducted, as appropriate, to assess the primary outcome of survival and to further elucidate the descriptive data. RESULTS: There was no difference in survival between the case and control groups, either when evaluated with univariate (34% vs 25%; P=.41) or multivariate (odds ratio=0.99; 95% CI, 0.96-1.02; P=.57) analyses. Blunt trauma was the most common mechanism in both groups, but penetrating trauma was more common in the control group (30% vs 9%; P=.003). Patients in the control group were also more likely to have no vital signs on initial assessment (62% vs 31%; P=.003). More patients in the case group were described as having clinical improvement after NT (34% vs 19%; P=.03). No complications of NT were reported in either group. CONCLUSIONS: There was no significant difference in survival between patients with prolonged versus short transport times who underwent NT. Patients with prolonged transport times were more likely to have sustained blunt trauma, have vital signs on EMS arrival, and to have clinical improvement after NT. PMID- 26152550 TI - Gold nanoparticles and vaccine development. AB - Mucosal vaccines constitute an advantageous immunization approach to achieve broad immunization against widespread diseases; however, improvements in this field are still required to expand their exploitation. As gold nanoparticles are biocompatible and can be easily functionalized with antigens, they have been proposed as carriers for the delivery of vaccines. The study of gold nanoparticles (AuNPs) in vaccinology has been of interest for a number of research groups in recent years and important advances have been made. This review provides a summary of the AuNPs synthesis methodologies and an updated overview of the current AuNPs-based vaccines under development. The implications of these advances for the development of new mucosal vaccines as well as future prospects for the field are discussed. PMID- 26152551 TI - Congenital stapes malformation: Rare conductive hearing loss in a patient with Waardenburg syndrome. AB - Waardenburg syndrome is a known autosomal dominant cause of congenital hearing loss. It is characterized by a distinctive phenotypic appearance and often involves sensorineural hearing loss. Temporal bone abnormalities and inner ear dysmorphisms have been described in association with the disease. However, middle ear abnormalities as causes of conductive hearing loss are not typically seen in Waardenburg syndrome. We discuss a case of an 8-year-old female who meets diagnostic criteria for Waardenburg syndrome type 3 and who presented with a bilateral conductive hearing loss associated with congenital stapes fixation. We discuss management strategy in this previously unreported phenotype. PMID- 26152552 TI - Paroxysmal nocturnal hemoglobinuria (PNH) and T cell large granular lymphocyte (LGL) leukemia--an unusual association: another cause of cytopenia in PNH. PMID- 26152553 TI - The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation. AB - Primary poor graft function (PGF) is a severe complication after allogeneic stem cell transplantation (SCT). The incidence, risk factors, and outcomes of PGF have not been well described, especially in the haploidentical SCT setting. We retrospectively reviewed patients who received haploidentical SCT at Peking University Institute of Hematology between January 1, 2011, and December 31, 2012. PGF was defined as persistent neutropenia (<=0.5 * 10(9) L(-1)), thrombocytopenia (platelets <=20 * 10(9) L(-1)), and/or hemoglobin <=70 g L(-1) after engraftment with hypocellular bone marrow and full donor chimerism, without concurrent graft-versus-host disease or disease relapse. Incidence was calculated from all patients. Of the 464 total patients, 26 (5.6 %) developed primary PGF. The risk factors were analyzed and compared with control patients with good graft function who were selected using the case-pair method. Finally, 104 patients were selected as a control group according to the matching conditions: (1) the type (acute leukemia, myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML)) and status (standard risk, high risk) of underlying disease, (2) sex, (3) year in which the transplantation was received, and (4) a 1:4 ratio of case control. No factors were found to be associated with primary PGF. Compared to cases with good graft function, patients with primary PGF experienced poor overall survival (34.6 vs. 82.7 %, p < 0.001). Of the 26 primary PGF patients, only nine achieved hematopoietic recovery and survived. In conclusion, primary PGF is a rare but life-threatening complication after haploidentical SCT, and effective therapies need to be explored. PMID- 26152554 TI - From Louisville to Morioka: where is now MILS? PMID- 26152555 TI - High incidence of engraftment syndrome after haploidentical allogeneic stem cell transplantation. AB - We determined the incidence, clinical manifestations, and outcomes of engraftment syndrome (ES) in haploidentical stem cell transplantation (SCT) recipients. We compared the incidence of ES between the patient group that received haploidentical SCT (n = 516) and the patient group that received HLA-identical sibling SCT (n = 393). The transplantations were performed in the Peking University People's Hospital in the period between October 2001 and October 2012. The ES incidence data were collected retrospectively. Patients that presented non infectious fever or skin rash within the 24-h window before or after the beginning of neutrophil recovery were diagnosed with ES in accordance with the Maiolino criteria. ES incidence in haploidentical SCT recipients (21.9%) was significantly higher than that in HLA-identical sibling SCT recipients (2.0%; P < 0.001). Major symptoms included fever (119/121, 98.3%), skin rash (98/121, 81.0%), and diarrhea (51/121, 42.1%), with the median time of +10 d (range: 6-20 d). The median C-reactive protein level of the ES group (99.0 mg/L; n = 13) was significantly higher than that of the non-ES group (13.9 mg/L; n = 38; P < 0.001). Similarly, the results showed that the median C3 plasma concentration of the ES group (1.30 g/L) was higher than that of the non-ES group (1.16 g/L, P = 0.003). ES was not associated with non-relapse mortality or overall survival. High incidence of ES was observed in haploidentical SCT recipients; however, ES did not predict poor clinical outcomes. PMID- 26152556 TI - Assay of bacteriorhodopsin stability on polycarbonate surface by using of FTIR ATR: a model of disk-based bioassays. AB - Bacteriorhodopsin (BR) is a transmembrane protein which able to transport protons through cell membrane and thus converting solar energy to electrical energy. Up to now different strategies have been used to immobilize BR. In the present study the BR has been immobilized on polycarbonate surface with two different methods. The functional groups of polycarbonate were modified in two ways (sulfuric acid, PDAC and HNO3) and then the BR was immobilized on two different modified polycarbonate surfaces. The modified surfaces were characterized by ATR-FTIR and AFM techniques. Afterward the activity of bounded BR to two different modified polycarbonate surfaces was measured. Our results show that BR bounded to modified polycarbonate surface with HNO3 (nitrated polycarbonate) has higher activity in comparison to modified with sulfuric acid (electrostatically bounded BR). Also the activities of both types of Bounded BR after 10 days were measured. The results showed that unlike electrostatically bounded BR, bounding BR to nitrated polycarbonate keeps its activity after 10 days. In conclusion, nitrated polycarbonate surface is a suitable candidate due to immobilizing BR in order to manufacture of BioCDs. PMID- 26152557 TI - MRI accurately identifies early murine mammary cancers and reliably differentiates between in situ and invasive cancer: correlation of MRI with histology. AB - MRI methods that accurately identify various stages of mouse mammary cancer could provide new knowledge that may have a direct impact on the management of breast cancer in patients. This research investigates whether we can accurately follow the progression from in situ to invasive cancer by the evaluation of in vivo and ex vivo MRI, and in comparison with histology as the gold standard for the diagnosis and staging of cancer. Six C3(1)SV40Tag virgin female mice, aged 12-16 weeks, were studied. At this age, these mice develop in situ cancer that resembles human ductal carcinoma in situ (DCIS). Fast spin-echo images of inguinal mammary glands were acquired at 9.4 T. After in vivo MRI, mice were sacrificed; inguinal mammary glands were excised and fixed in formalin for ex vivo MRI. Three-dimensional, volume-rendered, in vivo and ex vivo MR images were then correlated with histology. High-resolution ex vivo scans facilitated the comparison of in vivo scans with histology. The sizes of mammary cancers classified as in situ on the basis of histology ranged from 150 to 400 um in largest diameter, and the average signal intensity relative to muscle was 1.40 +/ 0.18 on T2 -weighted images. Cancers classified as invasive on the basis of histology were >400 um in largest diameter, and the average intensity relative to muscle on T2 -weighted images was 2.34 +/- 0.26. Using a cut-off of 400 um in largest diameter to distinguish between in situ and invasive cancers, a T2 weighted signal intensity of at least 1.4 times that of muscle for in situ cancer, and at least 2.3 times that of muscle for invasive cancer, 96% of in situ and 100% of invasive cancers were correctly identified on in vivo MRI, using histology as the gold standard. Precise MRI-histology correlation demonstrates that MRI reliably detects early in situ cancer and differentiates in situ from invasive cancers in the SV40Tag mouse model of human breast cancer. PMID- 26152558 TI - Differences in Longer-Term Smoking Abstinence After Treatment by Specialist or Nonspecialist Advisors: Secondary Analysis of Data From a Relapse Prevention Trial. AB - INTRODUCTION: Smokers receiving support in specialist centers tend to have a higher short-term quit rate, compared with those receiving support in other settings from professionals for whom smoking cessation is only a part of their work. We investigated the difference in longer-term abstinence after short-term smoking cessation treatment from specialist and nonspecialist smoking cessation services. METHODS: We conducted a secondary analysis of data from a randomized controlled trial of self-help booklets for the prevention of smoking relapse. The trial included 1088 short-term quitters from specialist stop smoking clinics and 316 from nonspecialist cessation services (such as general practice, pharmacies, and health trainer services). The difference in prolonged smoking abstinence from months 4 to 12 between specialist and nonspecialist services was compared. Multivariable logistic regression analyses were conducted to investigate the association between continuous smoking abstinence and the type of smoking cessation services, adjusted for possible confounding factors (including demographic, socioeconomic, and smoking history variables). RESULTS: The proportion of continuous abstinence from 4 to 12 months was higher in short-term quitters from specialist services compared with those from nonspecialist services (39% vs. 32%; P = .023). After adjusting for a range of participant characteristics and smoking variables, the specialist service was significantly associated with a higher rate of longer-term smoking abstinence (odds ratio: 1.48, 95% CI = 1.09% to 2.00%; P = .011). CONCLUSIONS: People who receive support to stop smoking from a specialist appear to be at lower risk of relapse than those receiving support from a nonspecialist advisor. PMID- 26152559 TI - Influence of maxillary advancement surgery on skeletal and soft-tissue changes in the nose - a retrospective cone-beam computed tomography study. AB - OBJECTIVES: Surgical correction of skeletal maxillary retroposition is often associated with changes in the morphology of the nose. Unwanted alar flaring of the nose is observed in many cases. The aim of the present study was therefore to investigate the influence of surgical advancement of the maxilla on changes in the soft-tissue morphology of the nose. Having a coefficient that allows prediction of change in the nasal width in Caucasian patients after surgery would be helpful for treatment planning. MATERIALS AND METHODS: All 33 patients included in this retrospective study were of Caucasian descent and had skeletal Class III with maxillary retrognathia. They were all treated with maxillary advancement using a combination of orthodontic and maxillofacial surgery methods. Two cone-beam computed tomography (CBCT) datasets were available for all of the study's participants (16 female, 17 male; age 24.3 +/- 10.4 years): the first CBCT imaging was obtained before the planned procedure (T0) and the second 14.1 +/- 6.4 months postoperatively (T1). Morphological changes were recorded three dimensionally using computer-aided methods (Mimics (Materialise NV, Leuven/Belgium), Geomagic (Geomagics, Morrisville/USA)). Statistical analysis was carried out using SPSS 21 for Mac. RESULTS: The mean sagittal advancement of the maxilla was 5.58 mm. The width of the nose at the alar base (Alb) changed by a mean of + 2.59 mm (+/-1.26 mm) and at the ala (Al) by a mean of + 3.17 mm (+/ 1.32 mm). Both of these changes were statistically highly significant (P = 0.000). The increase in the width of the nose corresponded to approximately half of the maxillary advancement distance in over 80 % of the patients. The nasolabial angle declined by an average of -6.65 degrees (+/-7.71 degrees ). CONCLUSIONS: Maxillary advancement correlates with a distinct morphological change in nasal width. This should be taken into account in the treatment approach and in the information provided to patients. PMID- 26152560 TI - Impact of Catheter Contact Force on Human Left Atrial Electrogram Characteristics in Sinus Rhythm and Atrial Fibrillation. AB - BACKGROUND: During left atrial mapping, optimal contact parameters minimizing variation secondary to catheter contact are not established. METHODS AND RESULTS: Across 30 patients undergoing first-time atrial fibrillation ablation, 1965 stable mapping points (1409 atrial fibrillation, 556 sinus rhythm), comprising 8 s contact force (CF) and bipolar electrogram data were analyzed. Points were taken in groups at locations with CF or catheter orientation actively changed between acquisitions. Complexes were less positive at higher CF (Spearman rho, 0.2; P<0.005, both rhythms). Increasing CF at a location significantly increased complex size, but only where initial CF was <10 g, and if the change was >=4.5 g in sinus rhythm and >=8 g in atrial fibrillation (P<0.0005, both rhythms): if initial CF was >=10 g, no change was observed, regardless of CF change (P>0.05, both). Atrial ectopics during sinus rhythm were observed more frequently when CF was >=10 g (P<0.0005). Increasing CF at a location was associated with an increase in the complex fractionated atrial electrogram interval confidence level score, but only if initial CF was <10 g and CF increased >=8 g (P=0.003). The dominant frequency and organization index were unaffected by CF (P>0.1 for both). Changing catheter orientation from perpendicular to parallel in atrial fibrillation was associated with smaller, more positive complexes (P=0.001 for both), but no changes in complex fractionated atrial electrogram scores, dominant frequency or organization index (P>0.08 for each). CONCLUSIONS: During left atrial electrogram mapping, including complex fractionated atrial electrogram but not spectral parameter mapping, CF and catheter orientation influence results: consequently, mapping CFs should be >=10 g to negate the influence of CF. CLINICAL TRIALS REGISTRATION: URL: http://clinicaltrials.gov/. Unique identifier: NCT01587404. PMID- 26152561 TI - Pulmonary fibrosis and exposure to steel welding fume. AB - BACKGROUND: Arc welders who have been exposed to high concentrations of steel welding fume for prolonged periods of time may develop pulmonary fibrosis but the nature of the fibrotic changes has been debated over the last 80 years without any clear international consensus. AIMS: To characterize the nature of the pulmonary fibrosis that develops in response to steel welding fume exposure and to provide a working hypothesis that would explain the findings of the existing research, to provide a platform for future research and to inform future occupational and clinical management of welders with pulmonary effects from welding fume. METHODS: Review of the world literature on pulmonary fibrosis and welding of steel in all languages using PubMed, with further secondary search of references in the articles found in the primary search. Google and Reference Manager were used as further confirmatory search tools. RESULTS: Only case series and case reports were found but these provided consistent evidence that the consequence of exposure to steel welding fume at high levels for a prolonged period of time is a type of pulmonary fibrosis similar to, and possibly the same as, respiratory bronchiolitis which eventually develops into desquamative interstitial pneumonia with ongoing exposure. CONCLUSIONS: Steel welding fume may cause an occupational respiratory bronchiolitis which may develop into de squamative interstitial pneumonia with ongoing exposure. This concept may explain the difficulties in interpreting the wider literature on welding fume and lung function at lower exposures and may also explain the increased risk of lung cancer in welders. PMID- 26152562 TI - Ticagrelor Versus Clopidogrel in Black Patients With Stable Coronary Artery Disease: Prospective, Randomized, Open-Label, Multiple-Dose, Crossover Pilot Study. AB - BACKGROUND: The burden of coronary artery disease (CAD) is high in blacks, highlighting the need for clinical research of antiplatelet agents in this population. We sought to evaluate platelet reactivity during loading and maintenance dosing of ticagrelor versus clopidogrel, and the pharmacokinetic profile of ticagrelor and its metabolite AR-C124910XX, in black patients with stable CAD taking low-dose aspirin (acetylsalicylic acid). METHODS AND RESULTS: In a multicenter, randomized, open-label, crossover study, 34 blacks with stable CAD receiving acetylsalicylic acid 75 to 100 mg/d were randomized to clopidogrel (600 mg, then 75 mg QD for 7-9 days) or ticagrelor (180 mg, then 90 mg BID for 7 9 days). After washout 10 to 14 days, patients switched regimens. The primary end point was platelet reactivity 2 hours post loading dose (P2Y12 reactivity units [PRU] measured by the VerifyNow assay). Least-squares mean PRU at 2 hours post loading dose was lower with ticagrelor (27.6) versus clopidogrel (211.2); least squares mean difference was -183.6 (95% confidence interval, -213.9 to -153.3; P<0.001). At all time points, the least-squares mean PRU was significantly lower, and the percent reduction in PRU from baseline was statistically greater, with ticagrelor versus clopidogrel. At 2 hours post dose, the prevalence of high on treatment platelet reactivity (>=208 PRU) was lower with ticagrelor (0%) than with clopidogrel (57.1%). Pharmacokinetic profiles of ticagrelor and AR-C124910XX were consistent with previous reports in stable CAD populations. CONCLUSIONS: In black patients with stable CAD receiving low-dose acetylsalicylic acid, ticagrelor provided a faster onset and greater degree of platelet inhibition than clopidogrel. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01523392. PMID- 26152563 TI - Genetic similarities between Cyclospora cayetanensis and cecum-infecting avian Eimeria spp. in apicoplast and mitochondrial genomes. AB - BACKGROUND: Cyclospora cayetanensis is an important cause for diarrhea in children in developing countries and foodborne outbreaks of cyclosporiasis in industrialized nations. To improve understanding of the basic biology of Cyclospora spp. and development of molecular diagnostic tools and therapeutics, we sequenced the complete apicoplast and mitochondrial genomes of C. cayetanensis. METHODS: The genome of one Chinese C. cayetanensis isolate was sequenced using Roche 454 and Illumina technologies. The assembled genomes of the apicoplast and mitochondrion were retrieved, annotated, and compared with reference genomes for other apicomplexans to infer genome organizations and phylogenetic relationships. Sequence variations in the mitochondrial genome were identified by comparison of two C. cayetanensis nucleotide sequences from this study and a recent publication. RESULTS: The apicoplast and mitochondrial genomes of C. cayetanensis are 34,155 and 6,229 bp in size and code for 65 and 5 genes, respectively. Comparative genomic analysis showed high similarities between C. cayetanensis and Eimeria tenella in both genomes; they have 85.6% and 90.4% nucleotide sequence similarities, respectively, and complete synteny in gene organization. Phylogenetic analysis of the genomic sequences confirmed the genetic similarities between cecum-infecting avian Eimeria spp. and C. cayetanensis. Like in other coccidia, both genomes of C. cayetanensis are transcribed bi-directionally. The apicoplast genome is circular, codes for the complete machinery for protein biosynthesis, and contains two inverted repeats that differ slightly in LSU rRNA gene sequences. In contrast, the mitochondrial genome has a linear concatemer or circular mapping topology. Eight single nucleotide and one 7-bp multiple-nucleotide variants were detected between the mitochondrial genomes of C. cayetanensis from this and recent studies. CONCLUSIONS: The apicoplast and mitochondrial genomes of C. cayetanensis are highly similar to those of cecum-infecting avian Eimeria spp. in both genome organization and sequences. The availability of sequence data beyond rRNA and heat shock protein genes could facilitate studies of C. cayetanensis biology and development of genotyping tools for investigations of cyclosporiasis outbreaks. PMID- 26152564 TI - Development of a (99m)Tc-labeled lactam bridge-cyclized alpha-MSH derivative peptide as a possible single photon imaging agent for melanoma tumors. AB - OBJECTIVE: Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target which has been used for melanoma imaging and therapy. In this work, a new lactam bridge alpha-MSH analog was labeled with (99m)Tc via HYNIC and EDDA/tricine as coligands including gamma aminobutyric acid (GABA) as a three carbon chain spacer between HYNIC and the N-terminus of the cyclic peptide. Also, stability in human serum, receptor bound internalization, in vivo tumor uptake, and tissue biodistribution were thoroughly investigated. METHODS: HYNIC-GABA-Nle CycMSHhept was synthesized using a standard Fmoc strategy. Labeling was performed at 95 degrees C and analysis involved instant thin layer chromatography and high performance liquid chromatography methods. The receptor bound internalization rate was studied in MC1 receptor expressing B16/F10 cells. Biodistribution of radiopeptide was studied in nude mice bearing B16/F10 tumor. RESULTS: Labeling yield of >98 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed efficient stability in the presence of human serum. The radioligand showed specific internalization into B16/F10 cells (12.45 +/- 1.1 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor-positive organs so that after 2 h the uptake in mouse tumor was 5.10 +/- 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 +/- 0.68 % ID/g at 2 h after injection). CONCLUSIONS: The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors. PMID- 26152565 TI - Personal power-frequency magnetic field exposure in women recruited at an infertility clinic: association with physical activity and temporal variability. AB - Current epidemiologic approaches for studying exposure to power-frequency magnetic fields and the risk of miscarriage are potentially biased due to lack of attention to the relationship of exposure with physical activity and within individual variability in exposures over time. This analysis examines these two issues using data from a longitudinal pilot study of 40 women recruited from an infertility clinic that contributed data for up to three 24-h periods separated by a median of 3.6 weeks. Physical activity was positively associated with peak exposure metrics. Higher physical activity within environments did not necessarily lead to higher peak exposures, suggesting that movement between and not within environments increases one's probability of encountering a high field source. Peak compared with central tendency metrics were more variable over time. Future epidemiology studies associated with peak exposure metrics should adjust for physical activity and collect more than 1 d of exposure measurement to reduce bias. PMID- 26152566 TI - Effect of 220Rn gas concentration distribution on its transmission from a delay chamber: evolving a CFD-based uniformity index. AB - (220)Rn mitigation can be achieved by delay chamber technique, which relies on the advantage of its short half-life. However, flow rate as well as inlet-outlet position for the delay chamber can have a significant impact on (220)Rn concentration distribution patterns and hence transmission factor. In the present study, computational fluid dynamics simulations to estimate the concentration distribution has been carried out in a chamber of 0.5 m(3) for the combination of six different inlet-outlet positions and five different flow rates. Subsequently, the transmission factor (TF) for the chamber was evaluated and found to be highly dependent on the flow rate and inlet-outlet positions. For ease of scale up, the dependency of TF on the flow rate and the inlet-outlet positions is best summarised by relative transmission factor (RTF), which is the ratio of the TFs for the case of inlet and outlet on different faces to that on the same face. PMID- 26152567 TI - Enteric neuromodulators and mucus discharge in a fish infected with the intestinal helminth Pomphorhynchus laevis. AB - BACKGROUND: In vertebrates, the presence of enteric worms can induce structural changes to the alimentary canal impacting on the neuroendocrine system, altering the proper functioning of the gastrointestinal tract and affecting the occurrence and relative density of endocrine cells (ECs). This account represents the first immunohistochemistry and ultrastructure-based study which documents the intimate relationship between the intestinal mucous cells and ECs in a fish-helminth system, investigating the potential effects of enteric neuromodulators on gut mucus secretion/discharge. METHODS: A modified dual immunohisto- and histochemical staining technique was applied on intestinal sections from both infected and uninfected fish. Sections were incubated in antisera to a range of neuromodulators (i.e. leu-enkephalin, met-enkephalin, galanin and serotonin) and the glycoconjugate histochemistry of the mucous cells was determined using a subsequent alcian blue - periodic acid Schiff staining step. Dual fluorescent staining on sections prepared for confocal laser scanning microscopy and transmission electron microscopy were also used to document the relationship between ECs and mucous cells. RESULTS: From a total of 26 specimens of Squalius cephalus sampled from the River Paglia, 16 (i.e. 62 %) specimens were found to harbour an infection of the acanthocephalan Pomphorhynchus laevis (average intensity of infection 9.2 +/- 0.8 parasites host(-1), mean +/- standard error). When acanthocephalans were present, the numbers of mucous cells (most notably those containing acidic or mixed glycoconjugates) and ECs secreting leu enkephalin, met-enkephalin, galanin, serotonin were significantly higher than those seen on sections from uninfected fish. The relationship between met enkephalin-like or serotonin-like ECs and lectin DBA positive mucous cells was demonstrated through a dual fluorescent staining. The presence of tight connections and desmosomes between mucous and ECs in transmission electron micrographs provides further evidence of this intimate relationship. CONCLUSIONS: The presence of P. laevis induces an increase in the number of enteric ECs that are immunoreactive to leu- and met-enkephalin, galanin, and serotonin anti-sera. The mucous cells hyperplasia and enhanced mucus secretion in the helminth infected intestines could be elicited by the increase in the number of ECs which release these regulatory substances. PMID- 26152568 TI - A multifaceted feedback strategy alone does not improve the adherence to organizational guideline-based standards: a cluster randomized trial in intensive care. AB - BACKGROUND: Organizational data such as bed occupancy rate and nurse-to-patient ratio are related to clinical outcomes and to the efficient use of intensive care unit (ICU) resources. Standards for these performance indicators are provided in guidelines. We studied the effects of a multifaceted feedback strategy to improve the adherence to these standards. METHODS: In a cluster randomized controlled study design the intervention ICUs received extensive monthly feedback reports, they received outreach visits and initiated a quality improvement team. The control ICUs received limited quarterly feedback reports only. We collected primary data prospectively within the setting of a Dutch national ICU registry over a 14-month study period. The target indicators were bed occupancy rate (aiming at 80 % or below) and nurse-to-patient ratio (aiming at 0.5 or higher). Data were collected per 8-h nursing shift. Logistic regression analysis was performed. For both study end points, the odds ratios (OR) for improvements at follow-up versus at baseline were calculated separately for control and intervention ICUs. RESULTS: We analyzed data on 67,237 nursing shifts. The bed occupancy rate did not improve in the intervention group compared to baseline (adjusted OR 0.88; 95 % confidence interval (CI), 0.62-1.27) or compared to control group (OR 0.67; 95 % CI 0.39-1.15). The nurse-to-patient ratio did not improve (OR 0.72; 95 % CI 0.41-1.26 compared to baseline and OR 0.65; 95 % CI 0.35-1.19 compared to control group). CONCLUSIONS: A multifaceted feedback intervention did not improve the adherence to guideline-based standards on the organizational issues bed occupancy rate and nurse-to-patient ratio in the ICU. The reasons may be a limited confidence in data quality, the lack of practical tools for improvement, and the relatively short follow-up. TRIAL REGISTRATION: ISRCTN: ISRCTN50542146. PMID- 26152569 TI - QTL mapping of thrips resistance in pepper. AB - KEY MESSAGE: A QTL for thrips resistance on pepper chromosome 6 was identified and validated. This QTL affects thrips larval development and explains 50% of the variation. Thrips is one of the most damaging pests in pepper (Capsicum). Resistance to thrips was identified in Capsicum annuum. This study was aimed at the elucidation of the genetic background of thrips resistance in Capsicum through QTL mapping. The QTL analysis was carried out for Frankliniella occidentalis resistance in an F2 population consisting of 196 plants derived from an interspecific cross between the highly resistant C. annuum AC 1979 as female parent and the highly susceptible C. chinense 4661 as male parent. Fifty-seven SSR, 109 AFLP, and 5 SNP markers were used to construct a genetic map with a total length of 1636 cM. Damage caused by larvae and the survival of first and second instar larval stages observed in a no-choice test were used as parameters of resistance. Interval mapping detected one QTL for each of these parameters, all co-localizing near the same marker on chromosome 6. Use of this marker as co factor in a multiple-QTL mapping analysis failed to uncover any additional QTLs. This QTL explained about 50% of the genetic variation, and the resistance allele of this QTL was inherited from the resistant parent. Thrips resistance was not linked to trichome density. PMID- 26152570 TI - Genome-wide association and genomic prediction of resistance to maize lethal necrosis disease in tropical maize germplasm. AB - KEY MESSAGE: Genome-wide association analysis in tropical and subtropical maize germplasm revealed that MLND resistance is influenced by multiple genomic regions with small to medium effects. The maize lethal necrosis disease (MLND) caused by synergistic interaction of Maize chlorotic mottle virus and Sugarcane mosaic virus, and has emerged as a serious threat to maize production in eastern Africa since 2011. Our objective was to gain insights into the genetic architecture underlying the resistance to MLND by genome-wide association study (GWAS) and genomic selection. We used two association mapping (AM) panels comprising a total of 615 diverse tropical/subtropical maize inbred lines. All the lines were evaluated against MLND under artificial inoculation. Both the panels were genotyped using genotyping-by-sequencing. Phenotypic variation for MLND resistance was significant and heritability was moderately high in both the panels. Few promising lines with high resistance to MLND were identified to be used as potential donors. GWAS revealed 24 SNPs that were significantly associated (P < 3 * 10(-5)) with MLND resistance. These SNPs are located within or adjacent to 20 putative candidate genes that are associated with plant disease resistance. Ridge regression best linear unbiased prediction with five-fold cross validation revealed higher prediction accuracy for IMAS-AM panel (0.56) over DTMA AM (0.36) panel. The prediction accuracy for both within and across panels is promising; inclusion of MLND resistance associated SNPs into the prediction model further improved the accuracy. Overall, the study revealed that resistance to MLND is controlled by multiple loci with small to medium effects and the SNPs identified by GWAS can be used as potential candidates in MLND resistance breeding program. PMID- 26152571 TI - Detection of an inversion in the Ty-2 region between S. lycopersicum and S. habrochaites by a combination of de novo genome assembly and BAC cloning. AB - KEY MESSAGE: A chromosomal inversion associated with the tomato Ty - 2 gene for TYLCV resistance is the cause of severe suppression of recombination in a tomato Ty - 2 introgression line. Among tomato and its wild relatives inversions are often observed, which result in suppression of recombination. Such inversions hamper the transfer of important traits from a related species to the crop by introgression breeding. Suppression of recombination was reported for the TYLCV resistance gene, Ty-2, which has been introgressed in cultivated tomato (Solanum lycopersicum) from the wild relative S. habrochaites accession B6013. Ty-2 was mapped to a 300-kb region on the long arm of chromosome 11. The suppression of recombination in the Ty-2 region could be caused by chromosomal rearrangements in S. habrochaites compared with S. lycopersicum. With the aim of visualizing the genome structure of the Ty-2 region, we compared the draft de novo assembly of S. habrochaites accession LYC4 with the sequence of cultivated tomato ('Heinz'). Furthermore, using populations derived from intraspecific crosses of S. habrochaites accessions, the order of markers in the Ty-2 region was studied. Results showed the presence of an inversion of approximately 200 kb in the Ty-2 region when comparing S. lycopersicum and S. habrochaites. By sequencing a BAC clone from the Ty-2 introgression line, one inversion breakpoint was identified. Finally, the obtained results are discussed with respect to introgression breeding and the importance of a priori de novo sequencing of the species involved. PMID- 26152572 TI - Novel glucosinolate composition lacking 4-methylthio-3-butenyl glucosinolate in Japanese white radish (Raphanus sativus L.). AB - KEY MESSAGE: Genetic analysis and gene mapping of the 4-methylthio-3-butenyl glucosinolate-less trait of white radish were performed and a white radish cultivar with new glucosinolate composition was developed. A spontaneous mutant having significantly low 4-methylthio-3-butenyl glucosinolate (4MTB-GSL) content was identified from a landrace of Japanese white radish (Raphanus sativus L.) through intensive evaluation of glucosinolate profiles of 632 lines including genetic resources and commercial cultivars using high-performance liquid chromatography (HPLC) analysis. A line lacking 4MTB-GSL was developed using the selected mutant as a gene source. Genetic analyses of F1, F2, and BC1F1 populations of this line suggested that the 4MTB-GSL-less trait is controlled by a single recessive allele. Using SNP and SCAR markers, 96 F2 plants were genotyped, and a linkage map having nine linkage groups with a total map distance of 808.3 cM was constructed. A gene responsible for the 4MTB-GSL-less trait was mapped between CL1753 and CL5895 at the end of linkage group 1. The genetic distance between these markers was 4.2 cM. By selfing and selection of plants lacking 4MTB-GSL, a new cultivar, 'Daikon parental line No. 5', was successfully developed. This cultivar was characterized by glucoerucin, which accounted for more than 90% of the total glucosinolates (GSLs). The total GSL content in roots was ca. 12 MUmol/g DW, significantly lower than those in common white radish cultivars. Significance of this line in radish breeding is discussed. PMID- 26152574 TI - Loci, genes, and mechanisms associated with tolerance to ferrous iron toxicity in rice (Oryza sativa L.). AB - KEY MESSAGE: A genome-wide association study in rice yielded loci and candidate genes associated with tolerance to iron toxicity, and revealed biochemical mechanisms associated with tolerance in contrasting haplotypes. Iron toxicity is a major nutrient disorder affecting rice. Therefore, understanding the genetic and physiological mechanisms associated with iron toxicity tolerance is crucial in adaptive breeding and biofortification. We conducted a genome-wide association study (GWAS) by exposing a population of 329 accessions representing all subgroups of rice to ferrous iron stress (1000 ppm, 5 days). Expression patterns and sequence polymorphisms of candidate genes were investigated, and physiological hypotheses related to candidate loci were tested using a subset of contrasting haplotypes. Both iron including and excluding tolerant genotypes were observed, and shoot iron concentrations explained around 15.5 % of the variation in foliar symptom formation. GWAS for seven traits yielded 20 SNP markers exceeding a significance threshold of -log10 P > 4.0, which represented 18 distinct loci. One locus mapped for foliar symptom formation on chromosome 1 contained two putative glutathione-S-transferases, which were strongly expressed under iron stress and showed sequence polymorphisms in complete linkage disequilibrium with the most significant SNP. Contrasting haplotypes for this locus showed significant differences in dehydroascorbate reductase activity, which affected the plants' redox status under iron stress. We conclude that maintaining foliar redox homeostasis under iron stress represented an important tolerance mechanism associated with a locus identified through GWAS. PMID- 26152573 TI - AGPase: its role in crop productivity with emphasis on heat tolerance in cereals. AB - KEY MESSAGE: AGPase, a key enzyme of starch biosynthetic pathway, has a significant role in crop productivity. Thermotolerant variants of AGPase in cereals may be used for developing cultivars, which may enhance productivity under heat stress. Improvement of crop productivity has always been the major goal of plant breeders to meet the global demand for food. However, crop productivity itself is influenced in a large measure by a number of abiotic stresses including heat, which causes major losses in crop productivity. In cereals, crop productivity in terms of grain yield mainly depends upon the seed starch content so that starch biosynthesis and the enzymes involved in this process have been a major area of investigation for plant physiologists and plant breeders alike. Considerable work has been done on AGPase and its role in crop productivity, particularly under heat stress, because this enzyme is one of the major enzymes, which catalyses the rate-limiting first committed key enzymatic step of starch biosynthesis. Keeping the above in view, this review focuses on the basic features of AGPase including its structure, regulatory mechanisms involving allosteric regulators, its sub-cellular localization and its genetics. Major emphasis, however, has been laid on the genetics of AGPases and its manipulation for developing high yielding cultivars that will have comparable productivity under heat stress. Some important thermotolerant variants of AGPase, which mainly involve specific amino acid substitutions, have been highlighted, and the prospects of using these thermotolerant variants of AGPase in developing cultivars for heat prone areas have been discussed. The review also includes a brief account on transgenics for AGPase, which have been developed for basic studies and crop improvement. PMID- 26152575 TI - Molecular characterization of novel LMW-i glutenin subunit genes from Triticum urartu Thum. ex Gandil. AB - KEY MESSAGE: A high level of genetic diversity was found in LMW-i genes from Triticum urartu, resulting in detection of 11 novel alleles. The variability detected could affect gluten quality. Low-molecular weight glutenin subunits are important in determining the viscoelastic properties of wheat dough. Triticum urartu Thum. ex Gandil., which is related to the A genome of polyploid wheat, has been shown as a good source of variation for these subunits. The present study evaluated the variability of LMW-i genes in this species. High polymorphism was found in the sequences analysed and resulted in the detection of 11 novel alleles, classified into two sets (Group-I and -II) showing unique SNPs and InDels. Both groups were associated with Glu-A3-1 genes from common wheat. In general, deduced proteins from Group-II genes possessed a higher proportion of glutamine and proline, which has been previously suggested to be related with good quality. Moreover, there were other changes compared to common wheat. This novel variation could affect dough quality. Additional epitopes for celiac disease were also detected, suggesting that these subunits could be highly reactive. The results showed that T. urartu could be an important source of genetic variability for LMW-i genes that could enlarge the genetic pool of modern wheat. PMID- 26152576 TI - QTL mapping of carrot resistance to leaf blight with connected populations: stability across years and consequences for breeding. AB - KEY MESSAGE: Combining biparental and multiparental connected population analyses was useful for the identification of 11 QTLs in two new genetic backgrounds of carrot resistance to Alternaria dauci and for breeding recommendations. Leaf blight due to the fungus Alternaria dauci is the major carrot foliar disease worldwide. Some resistance QTLs have been previously identified in one population, but the evaluation of additional genetic backgrounds with higher level of resistance would give opportunities for breeders to combine them by pyramiding. For this purpose, two segregating populations were evaluated twice across 4 years in the same environment (1) to compare the efficiency of the single vs. the connected populations approach for characterizing the new sources of carrot resistance to Alternaria dauci; (2) to evaluate the stability of QTLs over the years; and (3) to give recommendations to breeders for marker-assisted selection. Single and connected analyses were complementary; their combination allowed the detection of 11 QTLs. Connected analyses allowed the identification of common and specific QTLs among the two populations and the most favorable allele at each QTL. Important contrasts between allelic effects were observed with four and five most favorable alleles coming from the two resistant parental lines, whereas two other favorable alleles came from the susceptible parental line. While four QTLs were consistent across years, seven were detected within a single year. The heritabilities for both populations PC2 and PC3 were high (75 and 78%, respectively), suggesting that the resistance of carrot to A. dauci was little affected by these environmental conditions, but the instability of QTL over years may be due to changing environmental conditions. The complementarity between these parental lines in terms of interesting allelic combinations is also discussed. PMID- 26152577 TI - The interaction between felt touch and tactile consequences of observed actions: an action-based somatosensory congruency paradigm. AB - Action observation leads to a representation of both the motor aspect of an observed action (motor simulation) and its somatosensory consequences (action based somatosensory simulation) in the observer's brain. In the current electroencephalography-study, we investigated the neuronal interplay of action based somatosensory simulation and felt touch. We presented index or middle finger tapping movements of a human or a wooden hand, while simultaneously presenting 'tap-like' tactile sensations to either the corresponding or non corresponding fingertip of the participant. We focused on an early stage of somatosensory processing [P50, N100 and N140 sensory evoked potentials (SEPs)] and on a later stage of higher-order processing (P3-complex). The results revealed an interaction effect of animacy and congruency in the early P50 SEP and an animacy effect in the N100/N140 SEPs. In the P3-complex, we found an interaction effect indicating that the influence of congruency was larger in the human than in the wooden hand. We argue that the P3-complex may reflect higher order self-other distinction by signaling simulated action-based touch that does not match own tactile information. As such, the action-based somatosensory congruency paradigm might help understand higher-order social processes from a somatosensory point of view. PMID- 26152578 TI - Exposure to Leishmania spp. and sand flies in domestic animals in northwestern Ethiopia. AB - BACKGROUND: Human visceral leishmaniasis caused by Leishmania donovani is considered an anthroponosis; however, Leishmania-infected animals have been increasingly reported in L. donovani foci, and the role of these animals as reservoirs for human L. donovani infection remains unclear. METHODS: We conducted a study of domestic animals (goats, sheep, cows, dogs, and donkeys) in three L. donovani foci in northwestern Ethiopia. Domestic animals were screened for Leishmania DNA and for anti-L. donovani IgG. Serum anti-sand fly saliva antibodies were used as a marker of exposure to the vector sand fly, Phlebotomus orientalis. RESULTS: Of 546 animals tested, 32 (5.9%) were positive for Leishmania DNA, with positive animals identified among all species studied. Sequencing indicated that the animals were infected with parasites of the L. donovani complex but could not distinguish between L. infantum and L. donovani. A total of 18.9% of the animals were seropositive for anti-L. donovani IgG, and 23.1% of the animals were seropositive for anti-P. orientalis saliva IgG, with the highest seroprevalence observed in dogs and sheep. A positive correlation was found between anti-P. orientalis saliva and anti-L. donovani IgGs in cows, goats, and sheep. CONCLUSIONS: The detection of L. donovani complex DNA in the blood of domestic animals, the reported seroprevalence to the L. donovani antigen, and the widespread exposure to sand fly saliva among domestic animals indicate that they are frequently exposed to Leishmania infection and are likely to participate in the epidemiology of Leishmania infection, either as potential blood sources for sand flies or possibly as parasite hosts. PMID- 26152579 TI - Effects of a Statewide Protocol for the Management of Peritoneal Dialysis-Related Peritonitis on Microbial Profiles and Antimicrobial Susceptibilities: A Retrospective Five-Year Review. AB - ? BACKGROUND: Peritonitis is a major complication of peritoneal dialysis (PD) and is associated with significant morbidity and mortality. Early empirical antibiotic therapy is recommended, with the choice of agents guided by local resistance patterns. As routine use of specific antimicrobial agents can drive resistance, regular assessment of causative organisms and their susceptibility to empirical therapy is essential. ? METHODS: We conducted a retrospective review of all PD peritonitis cases and positive PD fluid cultures obtained over a 5-year period in Western Australia following the introduction of a statewide protocol for the initial management of PD peritonitis with intraperitoneal vancomycin and gentamicin. ? RESULTS: The incidence of PD peritonitis decreased from 1 in 16 patient months (0.75/year at risk) to 1 in 29 patient months (0.41/year at risk) over the 5 years. There were 1,319 culture-positive samples and 1,069 unique isolates identified. Gram-positive bacteria accounted for 69.9% of positive cultures, with vancomycin resistance averaging 2% over the study period. Gram negative bacteria accounted for 25.4% of positive cultures, with gentamicin resistance identified in an average of 8% of organisms. No increase in antimicrobial resistance to vancomycin or gentamicin occurred over the 5 years and there was no change in the proportion of gram-positive (69.9%), gram-negative (25.4%) or fungal (4.4%) organisms causing PD peritonitis. ? CONCLUSIONS: Over time, the peritonitis rates have dramatically improved although the profile of causative organisms remains similar. Empirical treatment of PD peritonitis with intraperitoneal vancomycin and gentamicin remains efficacious, with high levels of susceptibility and no evidence that the introduction of this statewide empirical PD peritonitis treatment protocol is driving resistance to these agents. PMID- 26152580 TI - The Effect of Fluid Overload on Clinical Outcome in Southern Chinese Patients Undergoing Continuous Ambulatory Peritoneal Dialysis. AB - ? BACKGROUND: Fluid overload is frequently present in dialysis patients and one of the important predictors of patient outcome. This study aimed to investigate the influence of fluid overload on all-cause mortality and technique failure in Southern Chinese continuous ambulatory peritoneal dialysis (CAPD) patients. ? METHODS: This was a post hoc study from a cross-sectional survey originally designed to investigate the prevalence and associated risk factors of fluid overload defined by bioimpedance analysis (BIA) in CAPD patients from January 1, 2008, to December 31, 2009. All 307 CAPD patients completing the original study were followed up until December 31, 2012. ? RESULTS: With a median follow-up period of 38.4 (19.2 - 47.9) months, 52 patients died. Patients with fluid overload (defined by extracellular water/total body water [ECW/TBW] >= 0.40) had a significantly higher peritonitis rate (0.016 vs 0.011 events/month exposure, p = 0.018) and cerebrovascular event rate (3.9 vs 1.1 events/100 patient years, p = 0.024) than the normal hydrated patients. Moreover, the results showed a significant rising of all-cause mortality (log-rank test = 5.59, p = 0.018), and a trend of increasing cardiovascular disease (CVD) mortality (log-rank test = 2.90, p = 0.089) and technique failure (log-rank test = 3.78, p = 0.052) in the patients with fluid overload. Fluid overload independently predicted all-cause mortality (hazard ratio [HR] = 12.98, 95%, confidence interval [CI] = 1.06 - 168.23, p = 0.042) and technique failure (HR = 13.56, 95% CI = 2.53 - 78.69, p = 0.007) in CAPD patients after adjustment for confounders. ? CONCLUSIONS: Fluid overload defined by BIA was an independent predictor for all-cause mortality and technique failure in CAPD patients. Continuous ambulatory peritoneal dialysis patients with fluid overload had a higher peritonitis rate, cardiovascular event rate, and poorer clinical outcome than those patients with normal hydration. PMID- 26152581 TI - The Association of Effluent Ca125 with Peritoneal Dialysis Technique Failure. AB - ? BACKGROUND AND OBJECTIVES: Cancer antigen 125 (CA125) reflects the mesothelial cell mass lining the peritoneal membrane in individual patients. A decline or absence of mesothelial cells can be observed with duration of peritoneal dialysis (PD) therapy. Technique failure due to peritoneal membrane malfunction becomes of greater importance after 2 years of PD therapy in comparison to the initial period. In this study, we aimed to investigate the association between effluent CA125 and technique survival in incident PD patients with a PD therapy period of at least 2 years. ? METHODS: Within the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a Dutch multicenter cohort including 2,000 incident dialysis patients, we identified all PD patients who developed technique failure after 2 years of PD therapy and randomly selected a number of them as cases in a nested case-control study. Controls were PD patients matched on follow up time without technique failure. Cases and controls were included if they had a dialysate specimen available within 24 +/- 6 months of PD therapy for retrospective CA125 determinations. Odds ratios for technique failure related to CA125 were estimated. We used a prospective cohort with incident PD patients from the Academic Medical Center-University of Amsterdam (AMC) for replication of effect estimates. In these patients, absolute risk of technique failure was estimated and related to effluent CA125 levels. ? RESULTS: A total of 38 PD patients were selected from the NECOSAD cohort. From the AMC cohort as replication cohort, 91 PD patients were included. Incidence rates of PD technique failure per 100 patient-years were 16.3 in the NECOSAD cohort and 12.9 in the AMC cohort. In both study populations CA125 levels below 12 - 14 kU/L were associated with an increased risk for technique failure. Technique survival rates in the AMC were 87% in patients with levels of CA125 above 12.1 kU/L and 65% for those with CA125 levels below this threshold after a maximum 5-year follow-up. ? CONCLUSIONS: Patients with high CA125 levels after at least 2 years of PD therapy tend to have better technique survival than patients with low CA125 levels. These results support the importance of effluent CA125 as a risk factor for dropout in long-term PD therapy. PMID- 26152582 TI - Chemorepulsion from the Quorum Signal Autoinducer-2 Promotes Helicobacter pylori Biofilm Dispersal. AB - The gastric pathogen Helicobacter pylori forms biofilms on abiotic and biotic surfaces. We have shown previously that H. pylori perceives the quorum signal autoinducer-2 (AI-2) as a chemorepellent. We report here that H. pylori chemorepulsion from endogenous AI-2 influences the proportions and spatial organization of cells within biofilms. Strains that fail to produce AI-2 (?luxS strains) or are defective for chemotaxis (?cheA strains) formed more spatially homogenous biofilms with a greater proportion of adherent versus planktonic cells than wild-type biofilms. Reciprocally, a strain that overproduced AI-2 (luxS(OP)) formed biofilms with proportionally fewer adherent cells. Along with the known AI 2 chemoreceptor, TlpB, we identified AibA and AibB, two novel periplasmic binding proteins that are required for the AI-2 chemorepulsion response. Disruptions in any of the proteins required for AI-2 chemotaxis recapitulated the biofilm adherence and spatial organization phenotype of the ?luxS mutant. Furthermore, exogenous administration of AI-2 was sufficient to decrease the proportion of adherent cells in biofilms and promote dispersal of cells from biofilms in a chemotaxis-dependent manner. Finally, we found that disruption of AI-2 production or AI-2 chemotaxis resulted in increased clustering of cells in microcolonies on cultured epithelial cells. We conclude that chemotaxis from AI-2 is a determinant of H. pylori biofilm spatial organization and dispersal. IMPORTANCE: Bacterial biofilms are ubiquitous in nature, but the mechanisms governing their assembly and spatial organization are not fully understood. Bacterial communication through quorum sensing has been shown to influence biofilm growth through the regulation of biofilm genes. Our study revealed a new role for quorum sensing in biofilms through rapid chemotactic responses to quorum signals. Specifically, we studied how chemorepulsion of Helicobacter pylori from the universal quorum signal autoinducer-2 (AI-2) shapes the spatial organization of its biofilms. We demonstrate that the chemorepulsive response of H. pylori to AI-2 is necessary to promote its dispersal from biofilms grown on both abiotic and biotic surfaces and is sufficient to promote dispersal in a chemotaxis-dependent manner. This work has broad implications for understanding the mechanisms by which endogenously produced microbial compounds shape the assembly and spatial organization of microbial communities in their environments. PMID- 26152583 TI - The Tat Inhibitor Didehydro-Cortistatin A Prevents HIV-1 Reactivation from Latency. AB - Antiretroviral therapy (ART) inhibits HIV-1 replication, but the virus persists in latently infected resting memory CD4(+) T cells susceptible to viral reactivation. The virus-encoded early gene product Tat activates transcription of the viral genome and promotes exponential viral production. Here we show that the Tat inhibitor didehydro-cortistatin A (dCA), unlike other antiretrovirals, reduces residual levels of viral transcription in several models of HIV latency, breaks the Tat-mediated transcriptional feedback loop, and establishes a nearly permanent state of latency, which greatly diminishes the capacity for virus reactivation. Importantly, treatment with dCA induces inactivation of viral transcription even after its removal, suggesting that the HIV promoter is epigenetically repressed. Critically, dCA inhibits viral reactivation upon CD3/CD28 or prostratin stimulation of latently infected CD4(+) T cells from HIV infected subjects receiving suppressive ART. Our results suggest that inclusion of a Tat inhibitor in current ART regimens may contribute to a functional HIV-1 cure by reducing low-level viremia and preventing viral reactivation from latent reservoirs. IMPORTANCE: Antiretroviral therapy (ART) reduces HIV-1 replication to very low levels, but the virus persists in latently infected memory CD4(+) T cells, representing a long-lasting source of resurgent virus upon ART interruption. Based on the mode of action of didehydro-cortistatin A (dCA), a Tat dependent transcription inhibitor, our work highlights an alternative approach to current HIV-1 eradication strategies to decrease the latent reservoir. In our model, dCA blocks the Tat feedback loop initiated after low-level basal reactivation, blocking transcriptional elongation and hence viral production from latently infected cells. Therefore, dCA combined with ART would be aimed at delaying or halting ongoing viral replication, reactivation, and replenishment of the latent viral reservoir. Thus, the latent pool of cells in an infected individual would be stabilized, and death of the long-lived infected memory T cells would result in a continuous decay of this pool over time, possibly culminating in the long-awaited sterilizing cure. PMID- 26152584 TI - A Duo of Potassium-Responsive Histidine Kinases Govern the Multicellular Destiny of Bacillus subtilis. AB - Multicellular biofilm formation and surface motility are bacterial behaviors considered mutually exclusive. However, the basic decision to move over or stay attached to a surface is poorly understood. Here, we discover that in Bacillus subtilis, the key root biofilm-controlling transcription factor Spo0A~Pi (phosphorylated Spo0A) governs the flagellum-independent mechanism of social sliding motility. A Spo0A-deficient strain was totally unable to slide and colonize plant roots, evidencing the important role that sliding might play in natural settings. Microarray experiments plus subsequent genetic characterization showed that the machineries of sliding and biofilm formation share the same main components (i.e., surfactin, the hydrophobin BslA, exopolysaccharide, and de novo formed fatty acids). Sliding proficiency was transduced by the Spo0A-phosphorelay histidine kinases KinB and KinC. We discovered that potassium, a previously known inhibitor of KinC-dependent biofilm formation, is the specific sliding-activating signal through a thus-far-unnoticed cytosolic domain of KinB, which resembles the selectivity filter sequence of potassium channels. The differential expression of the Spo0A~Pi reporter abrB gene and the different levels of the constitutively active form of Spo0A, Sad67, in Deltaspo0A cells grown in optimized media that simultaneously stimulate motile and sessile behaviors uncover the spatiotemporal response of KinB and KinC to potassium and the gradual increase in Spo0A~Pi that orchestrates the sequential activation of sliding, followed by sessile biofilm formation and finally sporulation in the same population. Overall, these results provide insights into how multicellular behaviors formerly believed to be antagonistic are coordinately activated in benefit of the bacterium and its interaction with the host. IMPORTANCE: Alternation between motile and sessile behaviors is central to bacterial adaptation, survival, and colonization. However, how is the collective decision to move over or stay attached to a surface controlled? Here, we use the model plant-beneficial bacterium Bacillus subtilis to answer this question. Remarkably, we discover that sessile biofilm formation and social sliding motility share the same structural components and the Spo0A regulatory network via sensor kinases, KinB and KinC. Potassium, an inhibitor of KinC-dependent biofilm formation, triggers sliding via a potassium perceiving cytosolic domain of KinB that resembles the selectivity filter of potassium channels. The spatiotemporal response of these kinases to variable potassium levels and the gradual increase in Spo0A~Pi levels that orchestrates the activation of sliding before biofilm formation shed light on how multicellular behaviors formerly believed to be antagonistic work together to benefit the population fitness. PMID- 26152585 TI - NS5A Domain 1 and Polyprotein Cleavage Kinetics Are Critical for Induction of Double-Membrane Vesicles Associated with Hepatitis C Virus Replication. AB - Induction of membrane rearrangements in the cytoplasm of infected cells is a hallmark of positive-strand RNA viruses. These altered membranes serve as scaffolds for the assembly of viral replication factories (RFs). We have recently shown that hepatitis C virus (HCV) infection induces endoplasmic reticulum derived double-membrane vesicles (DMVs) representing the major constituent of the RF within the infected cell. RF formation requires the concerted action of nonstructural action of nonstructural protein (NS)3, -4A, protein (NS)3 -4A, -4B, -5A, and -5B. Although the sole expression of NS5A is sufficient to induce DMV formation, its efficiency is very low. In this study, we dissected the determinants within NS5A responsible for DMV formation and found that RNA-binding domain 1 (D1) and the amino-terminal membrane anchor are indispensable for this process. In contrast, deletion of NS5A D2 or D3 did not affect DMV formation but disrupted RNA replication and virus assembly, respectively. To identify cis- and trans-acting factors of DMV formation, we established a trans cleavage assay. We found that induction of DMVs requires full-length NS3, whereas a helicase-lacking mutant was unable to trigger DMV formation in spite of efficient polyprotein cleavage. Importantly, a mutation accelerating cleavage kinetics at the NS4B-5A site diminished DMV formation, while the insertion of an internal ribosome entry site mimicking constitutive cleavage at this boundary completely abolished this process. These results identify key determinants governing the biogenesis of the HCV RF with possible implications for our understanding of how RFs are formed in other positive-strand RNA viruses. IMPORTANCE: Like all positive-strand RNA viruses, hepatitis C virus (HCV) extensively reorganizes intracellular membranes to allow efficient RNA replication. Double-membrane vesicles (DMVs) that putatively represent sites of HCV RNA amplification are induced by the concerted action of viral and cellular factors. However, the contribution of individual proteins to this process remains poorly understood. Here we identify determinants in the HCV replicase that are required for DMV biogenesis. Major contributors to this process are domain 1 of nonstructural protein 5A and the helicase domain of nonstructural protein 3. In addition, efficient DMV induction depends on cis cleavage of the viral polyprotein, as well as tightly regulated cleavage kinetics. These results identify key determinants governing the biogenesis of the HCV replication factory with possible implications for our understanding of how this central compartment is formed in other positive-strand RNA viruses. PMID- 26152588 TI - Mitral valve disease, atrial fibrillation, and device therapy. PMID- 26152586 TI - Genomics and Ecophysiology of Heterotrophic Nitrogen-Fixing Bacteria Isolated from Estuarine Surface Water. AB - The ability to reduce atmospheric nitrogen (N2) to ammonia, known as N2 fixation, is a widely distributed trait among prokaryotes that accounts for an essential input of new N to a multitude of environments. Nitrogenase reductase gene (nifH) composition suggests that putative N2-fixing heterotrophic organisms are widespread in marine bacterioplankton, but their autecology and ecological significance are unknown. Here, we report genomic and ecophysiology data in relation to N2 fixation by three environmentally relevant heterotrophic bacteria isolated from Baltic Sea surface water: Pseudomonas stutzeri strain BAL361 and Raoultella ornithinolytica strain BAL286, which are gammaproteobacteria, and Rhodopseudomonas palustris strain BAL398, an alphaproteobacterium. Genome sequencing revealed that all were metabolically versatile and that the gene clusters encoding the N2 fixation complex varied in length and complexity between isolates. All three isolates could sustain growth by N2 fixation in the absence of reactive N, and this fixation was stimulated by low concentrations of oxygen in all three organisms (~ 4 to 40 umol O2 liter(-1)). P. stutzeri BAL361 did, however, fix N at up to 165 umol O2 liter(-1), presumably accommodated through aggregate formation. Glucose stimulated N2 fixation in general, and reactive N repressed N2 fixation, except that ammonium (NH4 (+)) stimulated N2 fixation in R. palustris BAL398, indicating the use of nitrogenase as an electron sink. The lack of correlations between nitrogenase reductase gene expression and ethylene (C2H4) production indicated tight posttranscriptional-level control. The N2 fixation rates obtained suggested that, given the right conditions, these heterotrophic diazotrophs could contribute significantly to in situ rates. IMPORTANCE: The biological process of importing atmospheric N2 is of paramount importance in terrestrial and aquatic ecosystems. In the oceans, a diverse array of prokaryotes seemingly carry the genetic capacity to perform this process, but lack of knowledge about their autecology and the factors that constrain their N2 fixation hamper an understanding of their ecological importance in marine waters. The present study documents a high variability of genomic and ecophysiological properties related to N2 fixation in three heterotrophic isolates obtained from estuarine surface waters and shows that these organisms fix N2 under a surprisingly broad range of conditions and at significant rates. The observed intricate regulation of N2 fixation for the isolates indicates that indigenous populations of heterotrophic diazotrophs have discrete strategies to cope with environmental controls of N2 fixation. Hence, community-level generalizations about the regulation of N2 fixation in marine heterotrophic bacterioplankton may be problematic. PMID- 26152589 TI - Who should manage patients with chest pain in the emergency room? AB - A concise management scheme is discussed for the best outcome in patients with chest pain. PMID- 26152587 TI - TORC1 Regulates Developmental Responses to Nitrogen Stress via Regulation of the GATA Transcription Factor Gaf1. AB - The TOR (target of rapamycin [sirolimus]) is a universally conserved kinase that couples nutrient availability to cell growth. TOR complex 1 (TORC1) in Schizosaccharomyces pombe positively regulates growth in response to nitrogen availability while suppressing cellular responses to nitrogen stress. Here we report the identification of the GATA transcription factor Gaf1 as a positive regulator of the nitrogen stress-induced gene isp7(+), via three canonical GATA motifs. We show that under nitrogen-rich conditions, TORC1 positively regulates the phosphorylation and cytoplasmic retention of Gaf1 via the PP2A-like phosphatase Ppe1. Under nitrogen stress conditions when TORC1 is inactivated, Gaf1 becomes dephosphorylated and enters the nucleus. Gaf1 was recently shown to negatively regulate the transcription induction of ste11(+), a major regulator of sexual development. Our findings support a model of a two-faceted role of Gaf1 during nitrogen stress. Gaf1 positively regulates genes that are induced early in the response to nitrogen stress, while inhibiting later responses, such as sexual development. Taking these results together, we identify Gaf1 as a novel target for TORC1 signaling and a step-like mechanism to modulate the nitrogen stress response. IMPORTANCE: TOR complex 1 (TORC1) is an evolutionary conserved protein complex that positively regulates growth and proliferation, while inhibiting starvation responses. In fission yeast, the activity of TORC1 is downregulated in response to nitrogen starvation, and cells reprogram their transcriptional profile and prepare for sexual development. We identify Gaf1, a GATA-like transcription factor that regulates transcription and sexual development in response to starvation, as a downstream target for TORC1 signaling. Under nitrogen-rich conditions, TORC1 positively regulates the phosphorylation and cytoplasmic retention of Gaf1 via the PP2A-like phosphatase Ppe1. Under nitrogen stress conditions when TORC1 is inactivated, Gaf1 becomes dephosphorylated and enters the nucleus. Budding yeast TORC1 regulates GATA transcription factors via the phosphatase Sit4, a structural homologue of Ppe1. Thus, the TORC1-GATA transcription module appears to be conserved in evolution and may also be found in higher eukaryotes. PMID- 26152591 TI - Adsorption-induced changes of intramolecular optical transitions: PTCDA/NaCl and PTCDA/KCl. AB - Structural and optical properties of isolated perylene-3,4,9,10-tetracarboxylic acid dianhydride molecules adsorbed on (100) oriented NaCl and KCl surfaces were studied theoretically to analyze the recently observed red-shift of the optical excitation spectrum after adsorption (Muller et al., Phys. Rev. B, 2011, 83, 241203; Paulheim et al. Phys. Chem. Chem. Phys., 2013, 15, 4906). The ground state structures were obtained by periodic dispersion-corrected density functional theory (DFT) calculations. For the excited-state calculations, nonperiodic time-dependent DFT methods were applied for a cluster model embedded in point charges. The range-separated hybrid functional CAM-B3LYP was used. Correlation-consistent basis sets were used and the calculated excitation energies were extrapolated to the complete basis set limit. The shift of the first optical excitation energy was analyzed in terms of electronic and geometric contributions. It was found that both the distortion of the molecule due to the interaction with the surface and the electrostatic potential of the surface play an important role. PMID- 26152590 TI - Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial. AB - BACKGROUND: Current studies on salvage radiotherapy (sRT) investigate timing, dose-escalation and anti-hormonal treatment (ADT) for recurrent prostate cancer. These approaches could either be limited by radiation-related susceptibility of the anastomosis or by suspected side-effects of long-term ADT. A phase II protocol was developed to investigate the benefit and tolerability of regional hyperthermia with moderately dose-escalated radiotherapy. METHODS: The study hypothesis is that radio-thermotherapy is a safe and feasible salvage treatment modality. The primary endpoint is safety measured by frequency of grade 3+ genitourinary (GU) and gastrointestinal (GI) adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Feasibility is defined by number of hyperthermia treatments (n >= 7) and feasibility of radiotherapy according to protocol. Target volume delineation is performed according to the EORTC guidelines. Radiation treatment is administered with single doses of 2 Gy 5*/week to a total dose of 70 Gy. Regional hyperthermia is given 2*/week to a total of 10 treatments. RESULTS: European centres participate in the phase II trial using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The initiating centres were participants of the SAKK 09/10 study, where the same patient criteria and target volume definition (mandatory successful performed dummy run) were applied insuring a high standardisation of the study procedures. CONCLUSIONS: The introduced phase II study implements highly precise image-guided radiotherapy and regional hyperthermia. If the phase II study is found to be safe and feasible, a multicenter phase III study is planned to test whether the addition of regional hyperthermia to dose-intensified sRT improves biochemical control. PMID- 26152592 TI - Contained rupture of patched right ventricular outflow tracts during balloon sizing for percutaneous pulmonary valve implantation. AB - Transcatheter pulmonary valves are being used off-label to treat pulmonary insufficiency in patched right ventricular outflow tracts (RVOTs). We describe the first reported cases of patched RVOT rupture, during balloon sizing for percutaneous pulmonary valve implantation, in two patients with tetralogy of Fallot status post repair. Both RVOTs were too large for subsequent catheter based intervention. The ruptures remained stable over time, and both patients were managed conservatively with follow-up imaging. PMID- 26152593 TI - Recepteur d'origine nantais (RON), more than a kinase: Role in castrate-resistant prostate cancer. AB - Prostate cancer (PCA) is the second leading cause of cancer-related deaths in men in the United States. It is natural for a hormone-driven malignancy such as prostate cancer that androgen deprivation therapy (ADT) would be the preferred treatment for clinical disease management. However, after initial treatment response a vast majority of patients develop metastatic castrate-resistant prostate cancer (CRPC), which is fatal. While great headway has been made to understand the possible mechanisms that drive castrate-resistant disease, a bonafide cure remains elusive. Reactivation of androgen receptor (AR) signaling partly contributes to the emergence of CRPC. Here we briefly examine some of the known mechanisms of AR reactivation including intratumoral synthesis of androgens, modulation of AR coregulators, and AR variants with constitutive activity as well as activation of receptor tyrosine kinases. We primarily focus on the emerging dual function of the receptor tyrosine kinase (recepteur d'origine nantais; RON) as a traditional tyrosine kinase and transcription factor. We further discuss activation of RON as an alternate mechanism in the development of CRPC and available therapeutic approaches for clinical management of CRPC by combined inhibition of RON and AR. PMID- 26152594 TI - Fractionation of biogas plant sludge material improves metaproteomic characterization to investigate metabolic activity of microbial communities. AB - With the development of high resolving mass spectrometers, metaproteomics evolved as a powerful tool to elucidate metabolic activity of microbial communities derived from full-scale biogas plants. Due to the vast complexity of these microbiomes, application of suitable fractionation methods are indispensable, but often turn out to be time and cost intense, depending on the method used for protein separation. In this study, centrifugal fractionation has been applied for fractionation of two biogas sludge samples to analyze proteins extracted from (i) crude fibers, (ii) suspended microorganisms, and (iii) secreted proteins in the supernatant using a gel-based approach followed by LC-MS/MS identification. This fast and easy method turned out to be beneficial to both the quality of SDS-PAGE and the identification of peptides and proteins compared to untreated samples. Additionally, a high functional metabolic pathway coverage was achieved by combining protein hits found exclusively in distinct fractions. Sample preparation using centrifugal fractionation influenced significantly the number and the types of proteins identified in the microbial metaproteomes. Thereby, comparing results from different proteomic or genomic studies, the impact of sample preparation should be considered. All MS data have been deposited in the ProteomeXchange with identifier PXD001508 (http://proteomecentral.proteomexchange.org/dataset/PXD001508). PMID- 26152595 TI - Clinicopathological features of plasmablastic multiple myeloma: a population based cohort. AB - Multiple myeloma (MM) is a common malignant hematological disease displaying considerable heterogeneity. Historical data indicate a prognostic significance of plasmablastic morphology, proliferation, and adverse cytogenetics, but there is little knowledge on the degree of interdependency of these parameters. The aim of this study was to study the degree of overlap between these variables. In a consecutive population-based cohort of 194 untreated MM patients, morphology, and proliferation index, using immunohistochemical double staining for Ki-67 and CD138, was analyzed. In addition, cytogenetic changes were studied by karyotyping and fluorescence in situ hybridization (FISH). Plasmablastic morphology correlated with unfavorable clinical features, high proliferation index, high percentage of plasma cell infiltration in the bone marrow, abnormal karyotype, and del(13q) detected by karyotyping, which indicates that plasmablastic morphology reflects advanced and highly proliferative disease. However, plasmablastic morphology did not correlate with established adverse prognostic cytogenetics identified by FISH, for example, t(4;14), t(14;16) and del(17p). PMID- 26152597 TI - Oxygen flow during pediatric laryngoscopy: A simple solution. PMID- 26152601 TI - Comments on Experimentation in Twentieth-Century Agricultural Science. PMID- 26152596 TI - Yeast model identifies ENTPD6 as a potential non-obstructive azoospermia pathogenic gene. AB - Approximately ten percent of male infertility is caused by non-obstructive azoospermia (NOA), but the etiologies of many NOA remain elusive. Recently, a genome-wide association study (GWAS) of NOA in Han Chinese men was conducted, and only a few genetic variants associated with NOA were found, which might have resulted from genetic heterogeneity. However, those variants that lack genome wide significance might still be essential for fertility. Functional analysis of genes surrounding these variants in Drosophila identified some spermatogenesis essential genes. As a complementary method of Drosophila screening, SK1 background Saccharomvces cerevisiae was used as a model to screen meiosis-related genes from the NOA GWAS data in this study. After functional screening, GDA1 (orthologous to humanENTPD6) was found to be a novel meiosis-related gene. The deletion of GDA1 resulted in the failure of yeast sporulation. Further investigations showed that Gda1p was important for pre-meiotic S phase entry. Interestingly, the meiotic role of Gda1p was dependent on its guanosine diphosphatase activity, but not it's cytoplasmic, transmembrane or stem domains. These yeast data suggest that ENTPD6 may be a novel meiosis-associated NOA related gene, and the yeast model provides a good approach to analyze GWAS results of NOA. PMID- 26152602 TI - Ecotoxicological impact of engineered nanomaterials in bivalve molluscs: An overview. AB - The increasing production and application of engineered nanomaterials (ENMs) in consumer products over the past decade will inevitably lead to their release into aquatic systems and thereby cause the exposure to aquatic organisms, resulting in growing environmental and human health concern. Since bivalves are widely used in the monitoring of aquatic pollution, the aim of this review was to compile and analyse data concerning the ecotoxicity of ENMs using bivalve molluscs. The state of the art regarding the experimental approach, characterization, behaviour, fate, bioaccumulation, tissue and subcellular distribution and mechanisms of toxicity of ENMs in marine and freshwater bivalve molluscs is summarized to achieve a new insight into the mode of action of these nanoparticles in invertebrate organisms. This review shows that the studies about the toxic effects of ENMs in bivalves were conducted mainly with seawater species compared to freshwater ones and that the genus Mytilus is the main taxa used as a model system. There is no standardization of experimental approaches for toxicity testing and reviewed data indicate the need to develop standard protocols for ENMs ecotoxicological testing. In general, the main organ for ENM accumulation is the digestive gland and their cellular fate differs according to nano-specific properties, experimental conditions and bivalve species. Endosomal-lysosomal system and mitochondria are the major cellular targets of ENMs. Metal based ENMs mode of action is related mainly to the dissolution and/or release of the chemical component of the particle inducing immunotoxicity, oxidative stress and cellular injury to proteins, membrane and DNA damage. This review indicates that the aquatic environment is the potential ultimate fate for ENMs and confirms that bivalve molluscs are key model species for monitoring aquatic pollution by ENMs. PMID- 26152603 TI - Comparison of train-of-four ratios measured with Datex-Ohmeda's M-NMT MechanoSensorTM and M-NMT ElectroSensorTM. AB - Neuromuscular blockade is usually monitored using train-of-four (TOF) stimulation pattern. A TOF ratio of higher than 90 % is recommended to reduce the risk of adverse effects after anaesthesia. TOF ratio 90 % is used in clinical practice with all different neuromuscular monitors. Kinemyography (KMG) is one commercialized method to obtain numerical TOF values. We compared the KMG data obtained with Datex M-NMT MechanoSensorTM module, to the EMG data collected with Datex ElectroSensorTM, during clinical anaesthesia. Ipsilateral comparisons of the sensors were performed in 20 female patients during clinical procedures in propofol-remifentanil anaesthesia. After initial bolus dose of rocuronium (0.6 mg/kg), the spontaneous recovery of TOF ratio and T1 % were monitored. KMG gave higher TOF values than EMG. The difference was significant at KMG TOF values of 40 % or higher. After anaesthetic induction, but before administration of rocuronium, both TOF sensor values drifted from the TOF value of 1.0, showing either significant spontaneous fade (T1 > T4) or tendency of reverse fade (T1 < T4). KMG overestimates the recovery from neuromuscular blockade when compared with EMG. KMG and EMG cannot be used interchangeably, and TOF ratio 90 % cannot be considered as adequate level of recovery with all monitoring devices. PMID- 26152604 TI - Low dose dabigatran versus uninterrupted acenocoumarol for peri-procedural anticoagulation in atrial fibrillation catheter ablation. AB - BACKGROUND: Left atrial ablation for atrial fibrillation (AF) is associated with a transiently increased risk of thromboembolic and hemorrhagic events. We tested the hypothesis that the low dose dabigatran [110mg twice a day (bid)] can be safely used as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation in left atrial ablation procedures. METHODS AND RESULTS: A total of 149 consecutive patients undergoing pulmonary vein antral isolation for AF were included; 64 patients were on low dose dabigatran (110mg bid) and 85 patients were on acenocoumarol with therapeutic international normalized ratios. Two doses of dabigatran were withheld before the procedure and the drug was restarted 4hours after vascular hemostasis. Overall, the two groups were well matched. Hemorrhagic and thromboembolic complications were similar in both groups within 90days from the procedure (4.7% for the dabigatran group versus 9.4% for the acenocoumarol group; P=0.275). Major hemorrhage occurred in 1.6% in the dabigatran group versus 3.5% in the acenocoumarol group (P=0.462). A single thromboembolic event occurred in the dabigatran group (1.6%) versus 2 (2.4%) in the acenocoumarol group (P=0.734). Despite higher doses of intraprocedural heparin (P<0.01), the mean activated clotting time was significantly lower in patients who were on dabigatran than those on acenocoumarol (P<0.01). CONCLUSIONS: The low dose dabigatran regimen provides safe and effective peri procedural anticoagulation in patients undergoing left atrial ablation for AF compared with uninterrupted acenocoumarol therapy. PMID- 26152605 TI - Azithromycin inhibits IL-1 secretion and non-canonical inflammasome activation. AB - Deregulation of inflammasome activation was recently identified to be involved in the pathogenesis of various inflammatory diseases. Although macrolide antibiotics display well described immunomodulatory properties, presumably involved in their clinical effects, their impact on inflammasome activation has not been investigated. We compared the influence of macrolides on cytokine induction in human monocytes. The role of intracellular azithromycin-accumulation was examined by interference with Ca(++)-dependent uptake. We have also analysed the signalling cascades involved in inflammasome activation, and substantiated the findings in a murine sepsis model. Azithromycin, but not clarithromycin or roxithromycin, specifically inhibited IL-1alpha and IL-1beta secretion upon LPS stimulation. Interference with Ca(++)-dependent uptake abolished the cytokine modulatory effect, suggesting a role of intracellular azithromycin accumulation in the modulatory role of this macrolide. Azithromycin's inhibiting effects were observed upon LPS, but not upon flagellin, stimulation. Consistent with this observation, we found impaired induction of the LPS-sensing caspase-4 whereas NF kappaB signalling was unaffected. Furthermore, azithromycin specifically affected IL-1beta levels in a murine endotoxin sepsis model. We provide the first evidence of a differential impact of macrolides on the inflammasome/IL-1beta axis, which may be of relevance in inflammasome-driven diseases such as chronic obstructive pulmonary disease or asthma. PMID- 26152606 TI - Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe? AB - Tremor arises from an involuntary, rhythmic muscle contraction/relaxation cycle and is a common disabling symptom of many motor-related diseases such as Parkinson disease, multiple sclerosis, Huntington disease, and forms of ataxia. In the wake of anecdotal, largely uncontrolled, observations claiming the amelioration of some symptoms among cannabis smokers, and the high density of cannabinoid receptors in the areas responsible for motor function, including basal ganglia and cerebellum, many researchers have pursued the question of whether cannabinoid-based compounds could be used therapeutically to alleviate tremor associated with central nervous system diseases. In this review, we focus on possible effects of cannabinoid-based medicines, in particular on Parkinsonian and multiple sclerosis-related tremors and the common probable molecular mechanisms. While, at present, inconclusive results have been obtained, future investigations should extend preclinical studies with different cannabinoids to controlled clinical trials to determine potential benefits in tremor. PMID- 26152607 TI - Economic Evaluation of Community-Based HIV Prevention Programs in Ontario: Evidence of Effectiveness in Reducing HIV Infections and Health Care Costs. AB - Investments in community-based HIV prevention programs in Ontario over the past two and a half decades are assumed to have had an impact on the HIV epidemic, but they have never been systematically evaluated. To help close this knowledge gap, we conducted a macro-level evaluation of investment in Ontario HIV prevention programs from the payer perspective. Our results showed that, from 1987 to 2011, province-wide community-based programs helped to avert a total of 16,672 HIV infections, saving Ontario's health care system approximately $6.5 billion Canadian dollars (range 4.8-7.5B). We also showed that these community-based HIV programs were cost-saving: from 2005 to 2011, every dollar invested in these programs saved about $5. This study is an important first step in understanding the impact of investing in community-based HIV prevention programs in Ontario and recognizing the impact that these programs have had in reducing HIV infections and health care costs. PMID- 26152609 TI - Dipyrrolylquinoxaline difluoroborates with intense red solid-state fluorescence. AB - A set of organic fluorescent dyes of dipyrrolylquinoxalines (PQs ) and their BF2 complexes (BPQs ) were synthesized from commercial reagents, and were characterized by their X-ray structural analysis, and optical and electrochemical properties. BPQs showed intense broad absorption in the visible region in the solution-state. In comparison with that of PQs , there is an over 110 nm red shift of the absorption maximum in the BPQs (up to 583 nm). Interestingly, dyes all exhibit red solid-state fluorescence with moderate to high fluorescence quantum yields except for PQ which showed bright yellow solid-state fluorescence. X-ray structures of BPQs showed the planar structure of quinoxaline with one pyrrole unit via the BF2 chelation and the almost perpendicular orientation of the uncoordinated pyrrole to the NBN core plane (the dihedral angle of 70-73 degrees ). The extended pi-conjugation was in good agreement with the observed red-shift of the spectra. These dyes formed well-ordered intermolecular packing structures via the intermolecular hydrogen bonding between the N atoms of quinoxaline moieties and the NH units of adjacent pyrroles. The lack of pi-pi stacking in their crystal packing structures may explain the interestingly intense solid-state fluorescence of these dyes. PMID- 26152608 TI - Improving Adherence to Care Among "Hard to Reach" HIV-Infected Patients in Argentina. AB - Many HIV-infected patients fail to achieve undetectable viral load and are not retained in care. This pilot study examined patients lost to care in public and private clinics in Buenos Aires, Argentina. The impact of patient and provider interventions was compared separately and collectively. In Phase 1, participants prescribed antiretrovirals and non-adherent to treatment in the prior 3-6 months (n = 60) were randomized to patient intervention or standard of care (SOC) and assessed over 12 months. In Phase 2, providers were trained in interviewing techniques and 60 additional patients were randomized to patient intervention or SOC condition. Averaged across patient intervention status, Phase 2 provider intervention patients reported the most improved adherence and viral suppression at 6 and 12 months. Adherence in "patient intervention only" improved at midpoint and returned to baseline at 12 months. Results suggest provider training sustained patient adherence and viral suppression among "hard to reach" patients. PMID- 26152610 TI - Red-light running rates at five intersections by road user in Changsha, China: An observational study. AB - The red-light running rate by type of road users has not been reported in China so far. We conducted an observation study to report the violation rate in Changsha, China. Portable digital devices were used to record red-light running violations at five selected intersections. The observation was performed for three days (weekday, weekend and holiday), four time periods per day and an hour per time period (peak and off-peak hours in the morning and in the afternoon). Violation rate was calculated as number of violations divided by total number of vehicles/pedestrians*100%. We used adjusted violation rate ratio (VRR) to quantify the effects of type of day and time period based on Poisson model. Totally, 162,124 vehicles (including motor vehicles, motorcycles and bicycles) and 31,649 pedestrians were recorded. The red-light running rate was 0.14% for motor vehicle drivers, far lowering than those for motorcyclists (18.64%), bicyclists (18.74%) and pedestrians (18.54%). The rate on holiday was 1.89 times that on weekday for drivers. The rate for motorcyclists was high in off-peak hours (adjusted VRR: 1.11), but low on weekend and on holiday (adjusted VRRs: 0.80 and 0.65). The rate for bicyclists was 32% lower on weekend than on weekday. For pedestrians, the rates were high on weekend and holiday and in off-peak hours (adjusted VRR: 1.09, 1.67 and 1.30). The red-light running rate of motor vehicle drivers is far lower than those for motorcyclists, bicyclists and pedestrians. The effects of type of day and time period on violation rate vary with road users, indicating the type of day and time period should be considered when developing and implementing interventions to reduce red-light running of different road users. PMID- 26152612 TI - Psychometric properties of the Jefferson Scale of Empathy-Health Professional Student's version: An Italian validation study with nursing students. AB - This methodological study was conducted to test the psychometric properties of the Jefferson Scale of Empathy-Health Professional Student's version (JSE-HPS), in a convenience sample of 797 Italian nursing students and to describe their empathic engagement. Data were subjected to exploratory and confirmatory factor analysis, test-retest, correlation analysis, t-test, and analysis of variance method. Principal component factor extraction with Oblimin rotation on the first half of the sample was conducted. The analysis suggested a three-factor solution for 14 items: "compassionate care/emotional engagement," "perspective-taking," and "standing in the patient's shoes." Confirmatory factor analysis on the second half of the sample showed good fit indexes for the 14-item solution, indicated by the exploratory factor analysis, and the 20 item solution of the scale, with the exception of one item. Test-retest correlation was 0.50 (P < 0.001) for the overall scale. Results from group comparisons and correlations are also provided and discussed. The Italian version of the JSE-HPS is a psychometrically sound tool. The translated 20-item solution is also suitable to carry out cross cultural comparisons. PMID- 26152611 TI - Transcriptional network profile on synovial fluid T cells in psoriatic arthritis. AB - The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL) 23Rp19-, FOXP3- and related orphan receptor gamma T (RORgammat)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1beta, IL-2, IL-6, IL-21 and interferon (INF)-gamma were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4(+)CD25(-), CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg, and either mean fluorescence intensity (MFI) of FOXP3(+) on CD4(+) Treg or MFI of classic IL-6 receptor (IL-6R) alpha expression on CD4(+)CD25(-) helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-gamma were not detectable, whereas IL-6 and IL-1beta levels were higher than in SF of non inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORgammat proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg cells and brighter MFI of IL-6Ralpha were observed both on CD4(+)CD25(high)- and CD4(+)CD25(-) T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1beta and gammaC cytokines in the polarization and plasticity of Th17 and Treg cells, which might participate in the perpetuation of joint inflammation in PsA patients. PMID- 26152613 TI - Molecular typing for detection of high-risk human papillomavirus is a useful tool for distinguishing primary bladder carcinoma from secondary involvement of uterine cervical carcinoma in the urinary bladder. AB - AIMS: For patients with carcinoma of the urinary bladder and uterine cervix, distinguishing between metastasis and a second primary carcinoma has significant prognostic and therapeutic implications. The aim of this study was to investigate the prevalence of high-risk human papillomavirus (HR-HPV) in cervical carcinoma with secondary involvement of the bladder and primary bladder carcinoma, in order to explore whether the detection of HR-HPV could help to differentiate between the two. METHODS AND RESULTS: Paired bladder and cervix carcinoma specimens from 37 patients with cervical carcinoma with bladder involvement, four patients with bladder carcinoma with uterine cervical involvement and two patients with double primaries were studied with quantitative multiplex polymerase chain reaction and chromogenic in-situ hybridization. Three hundred and seventy-five bladder carcinomas and 220 cervical carcinomas were analysed as controls. All cases of cervical carcinoma with bladder involvement showed concordant HR-HPV-positive patterns. The four cases of bladder carcinoma with uterine involvement were negative for HR-HPV. HR-HPV was detected in the cervical carcinoma but not in the bladder carcinoma of the patients with double primaries. HR-HPV was detected in 91.9% of cervical carcinomas but in none of the bladder carcinomas in the control group. CONCLUSIONS: Molecular typing for HR-HPV detection is useful to distinguish bladder carcinoma from secondary involvement of cervical carcinoma. PMID- 26152614 TI - Associations between trematode infections in cattle and freshwater snails in highland and lowland areas of Iringa Rural District, Tanzania. AB - The epidemiology of trematode infections in cattle was investigated within highland and lowland areas of Iringa Rural District, in southern Tanzania. Fecal samples were collected from 450 cattle in 15 villages at altitudes ranging from 696 to 1800 m above the sea level. Freshwater snails were collected from selected water bodies and screened for emergence of cercariae. The infection rates in cattle were Fasciola gigantica 28.2%, paramphistomes 62.8% and Schistosoma bovis 4.8%. Notably, prevalence of trematode infections in cattle was much higher in highland (altitude > 1500 m) as compared with lowland (altitude < 1500 m) areas and was statistically significant (P-value = 0.000) for F. gigantica and paramphistomes but not for S. bovis. The snails collected included Lymnaea natalensis, Bulinus africanus, Bulinus tropicus, Bulinus forskali, Biomphalaria pfeifferi, Melanoides tuberculata and Bellamya constricta with a greater proportion of highland (75%) than lowland (36%) water bodies harbouring snails. Altitude is a major factor shaping the epidemiology of F. gigantica and paramphistomes infections in cattle in Iringa Rural District with greater emphasis upon control needed in highland areas. PMID- 26152615 TI - Effect of palm oil (Elaeis guineensis) tocotrienols on mesenteric adipose tissue deposition and the expression of 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1) in adrenalectomized rats treated with dexamethasone. AB - OBJECTIVES: A study was done to investigate the effect of palm oil (Elaeis guineensis) tocotrienols on (1) rats mesenteric adipose tissue deposition (2) and 11beta-HSD1 enzyme expression in mesenteric adipocyte. There is a necessity to find an inhibitor for the 11beta-HSD1 enzyme which enhances the proliferation of mesenteric adipocyte tissue therefore curbing the onset of metabolic syndrome. MATERIAL AND METHODS: A total of 35 male Spraque Dawley rats were divided into 5 different groups, i.e., a baseline control group (n=7), a sham operated group (n=7) and three experimental adrenalectomised groups (ADR) (n=21). Each of the experimental ADR group was given intramuscular dexamethasone (Dexa) with a dose of 120 MUg/kg after 2 weeks post adrenalectomy and were divided into adrenalectomised control (n=7), Glycyrrhizic acid (GCA) treated (dose=120 mg/kg/day; n=7) and Palm Tocotrienol treated (dose=60 mg/kg/day; n=7) groups. These various treatments were given 6 days a week for 8 weeks via gastric gavage (following 2 weeks of adrenalectomy). Data is expressed as mean +/- standard error mean (SEM), compared to each other using one-way analysis-of-variance (ANOVA) followed by Tukey's post hoc test and then a t-test. RESULTS: The results show that palm tocotrienol tend to slightly increase mesenteric adipose tissue deposition in rats. However, palm tocotrienol was also found to have potential in inhibiting the expression of 11beta-HSD1 enzyme in mesenteric adipocytes. CONCLUSIONS: This study suggests palm tocotrienol inhibits 11beta-HSD1 enzyme expression and activity. PMID- 26152616 TI - Effect of Exercise on Pulmonary Function Tests in Obese Malaysian Patients. AB - BACKGROUND AND AIMS: Obesity has taken the 21st century by storm, posing negative effects on of the various facades of health, healthcare and global economy. With regards to pulmonary performance, numerous studies have proven the detrimental effects of obesity while reinstating the positive effects of weight loss on overall pulmonary function. However, effects of exercise on pulmonary function and correlation between changes in pulmonary function test with weight loss have yet to be described. We performed a prospective interventional study to determine the effects of regular exercise on Pulmonary Function Tests (PFT) and ascertain the relationship between weight loss and change in PFT in obese patients. MATERIALS AND METHODS: Twenty-five obese patients were enrolled, giving an 80% power of study. Baseline weight and PFT consisting of FEV1, FVC, TLC, mean ERV and VC were recorded prior to commencement of the 8 week long Standard Exercise Regimen (SER). PFT and weight were recorded again at the end of 8 weeks. RESULTS: All parameters of the PFT studied improved significantly with exercise. The participants lost an average of 1kg of body weight post-exercise (p<0.0005). The correlations between mean changes in weight and PFT were negligible. CONCLUSIONS: A period of supervised regular exercise improves the pulmonary function of obese patients and this improvement is independent of the amount of weight loss. Hence, SER should be recommended to all obese patients, especially when bariatric surgery is desired. PMID- 26152617 TI - Pregnant and severe acute abdominal pain: A surgical diagnostic dilemma. AB - Acute abdominal pain in pregnancy remains a surgical conundrum. A 25-year-old primigravid at 29 weeks gestation presented with a two-week history of epigastric pain, nausea and vomiting. She had a distended abdomen consistent with a full term gravid uterus; tender at the epigastric and right hypochondrium suggestive of small bowel obstruction or acute appendicitis. Abdominal ultrasound was inconclusive but abdominal Computed Tomography (CT) suggested small bowel volvulus. An exploratory laparotomy revealed a segmental jejunal volvulus and small bowel diverticulum contributing to the volvulus. A short segmental bowel resection was performed. Histopathology confirmed a Meckel's Diverticulum. The patient recovered well but underwent premature labour 10 days later. Small bowel obstruction secondary to Meckel's diverticulum is rare in pregnancy. In an acute gestational abdomen, clinical examination is key. Radiological imaging may be helpful, whilst surgical intervention is confirmatory and therapeutic in the event of an obstructive volvulus. PMID- 26152618 TI - Adductor accessorius - an unusual supernumerary adductor muscle of thigh. AB - The knowledge of variant anatomy of medial compartment of thigh is extremely important in surgical procedures requiring obturator nerve block. The nerve block is also recommended for providing additional analgesia following major knee surgeries and for relieving painful adductor muscle spasm. The interfascial injection technique is commonly followed in ultrasound guided obturator nerve block. For this procedure it is imperative to identify the adductor muscles on sonography to inject the anesthetic solution in the intermuscular fascial planes. The presence of an additional muscle can prove useful in myocutaneous flap surgeries for reconstruction especially of perineum. We hereby report a case of such an anomalous supernumerary adductor muscle present between adductor brevis and proximal part of adductor magnus, in an adult Indian male cadaver, recorded during routine dissection in Department of Anatomy, Vardhman Mahavir Medical College and Safdarjung Hospital. The muscle was innervated by the posterior division of obturator nerve. The morphology, embryological basis and clinical aspects are also discussed. PMID- 26152619 TI - Rare atypical vascular pattern of subscapular artery: Anatomico-clinical insight. AB - BACKGROUND AND OBJECTIVE: The use of muscles of scapular region in transposition and reparative surgery has made the anatomical knowledge of axillary artery and its branches imperative. The subscapular arterial tree is frequently used as a source of microvascular grafts to replace damaged or diseased portion of arteries especially in upper and lower limbs. This investigation is aimed to study the variation in branching pattern of the third part of axillary artery. MATERIALS AND METHODS: Routine educational cadaveric dissection of a young adult Indian male cadaver. RESULTS: The present article highlights a rare variation of the subscapular artery and its branches. The subscapular artery displayed a unique pattern of trifurcation. Its branches were seen supplying serratus anterior, subscapularis, latissimus dorsi and teres major muscles. CONCLUSIONS: The study focuses on a new variation of the subscapular artery which could prove useful for interventional radiologists and surgeons in reconstructive surgeries. PMID- 26152620 TI - Knowledge of Emergency Department Triage nurses in management of patients with mental health needs: comparisons with the Triage Model of Lazio (TLM). AB - OBJECTIVES: To refer the current competences of Triage Nurses (TRNs) assessing the person with metal health problems in Emergency Departments (ED), and the impact of the Triage Lazio Model (TLM) upon it. MATERIALS AND METHODS: An anonymous questionnaire was administered to ED TRNs of the Lazio Region. Standardized Cronbach's alpha was used for reliability estimation. RESULTS: The Cronbach's alpha was 0.4. Two hundred ninety-nine TRNs were interviewed: 66% women, 47% aged 31-40 years, 60% followed TLM. The consideration of the patient as 'one who comes out of the normal', 'a person with altered functions of mind or mental function' and as 'hostile, aggressive and unpredictable' was reported more by females in comparison to the males (OR=1.76; OR=3.50; OR=1.79); TRNs who have not followed the course on TLM had higher probability to consider 'hostile, aggressive and unpredictable' the psychiatric patients (OR=1.87) in comparison with other Triage courses; those who have taken a course on Triage but at least 3 years ago, had a lower probability to consider as 'one who comes out of the normal' (OR=0.55). CONCLUSIONS: having followed the course TLM, having participated in a recent triage course, male gender, and the seniority in this job appear to be contributing factors for a proper management of psychiatric patients. Continuous improvement of specific knowledge and skills for the management of patients with mental health needs are mandatory. PMID- 26152621 TI - An insight into the harmful effects of soy protein: A review. AB - Soy protein (SP) is a protein derived from soybean meal. SP is obtained from the removal of the outer shell of soybean and the fatty acid. The dietary supplementation of SP was was reported to have positive effects on human health. Therefore, the attention towards SP is increasing among the consumers, industrialist and researchers. However, the side effects and toxicity related to SP was not summarized, to date. This review summarized the toxic effects such as hormonal disturbances, carcinogenic and organotoxicity of SP based on the clinical and experimental studies. The review mainly focused on the effect of soy isoflavone-genistein on various organs. The main aim of the present review is to increase the public awareness on the harmful effect of SP on the various health aspects and draw the attention of the health care personnel and researchers. PMID- 26152622 TI - Do intramedullary implants improve survival in elderly patients with trochanteric fractures? A retrospective study. AB - BACKGROUND AND HYPOTHESIS: There is currently no consensus regarding superiority of the intramedullary fixation over the sliding hip screw. Regional variation remains high and not backed up by solid evidence. Given these premises we aimed to analyze weather implant preference can influence the postoperative survival. Secondary objectives were determining the trend for implant choice and confounding factors associated with intramedullary nails compared to sliding hip screws. PATIENTS AND METHODS: Retrospective data was obtained from patient charts with the main diagnosis of extracapsular/ trochanteric fractures, corresponding to ICD S72.1 codes. Between 2008-2012, 441 patients underwent osteosynthesis with a dynamic hip screw and 155 with intramedullary nail respectively. The living status was determined by comparing the patient identification number against the national population evidence records. RESULTS: The lifetable shows similar survival for both implants over the 5 year period. The yearly mortality was 19.4% for the dynamic hip screw and 21.8% for the intramedullary implant respectively, even though the later were used predominantly in older patients. This age difference is significant according to both parametric and non-parametric tests whereas duration of hospital stay are similar. We found a clear increase in the proportion of intramedullary implants, for a total of 11.2% over the 5 year period. There is no difference for the one year mortality and overall survival between sliding screw plates and intramedullary constructs. CONCLUSIONS: A clear increase in the use of intramedullary implants for trochanteric fractures was observed. This is even more apparent for older ages, presumably due to an higher surgeon confidence with the biomechanical stability of the intramedullary constructs. PMID- 26152623 TI - Immediately loaded dental implants bioactivated with platelet-rich plasma (PRP) placed in maxillary and mandibular region. AB - BACKGROUND AND AIM: Dental implants have today deeply changed the dental field. In fact, after almost 50 years, the permanent placement of a titanium screw with an attached tooth have, step by step, changed the society's standard toward a permanently replacement of missed or severely damaged teeth. In fact, the host of benefits born from dental implants have affected both patients and dental professionals. The aim of the present study is to report the outcomes of an implant therapy protocol supporting fixed prostheses implanted soon after extractions and loaded with flapless guided surgery by a 3D software planning. MATERIALS AND METHODS: 37 patients, requiring rehabilitation of booth dental arches with a one-to-one technique, were enrolled in a follow-up study plan which established clinical and radiological examinations on the day after surgery, seven months and one year later. Platelet Rich Plasma (PRP), in combination with autogenous bone, organic bone material and organic bone substitutes, was used before implant-prosthetic rehabilitation with an its prompt loading just before the implant insertion phase. RESULTS: Definitive restorations were delivered at 6 12 months after surgical procedure. One year after loading there were no dropouts and no failure of the definitive prosthesis. Furthermore, the feedback from patients resulted positive. CONCLUSIONS: Patients resulted satisfied both aesthetically and functionally regarding these types of prosthetic reconstructions made at the time. PMID- 26152624 TI - Drain tip cultures do not predict infections in primary total knee arthroplasty. AB - BACKGROUND AND AIM: The possibility to predict surgical site infections development could be of high prognostic value. We aimed to investigate whether cultures obtained from the tip of the closed passive wound drain may provide early signs of progression towards periprosthetic joint infections. MATERIALS AND METHODS: We performed an observational study on consecutive primary total knee arthroplasties performed in our department over 4 years by two high volume surgeons (it means they do a lot of arthroplasties/year; it is orthopedics specific). A total of 284 knees in 257 patients were included. Follow up was available for an average of 18.7 months. There were no simultaneous procedures. RESULTS: Nineteen (6.69%) drain tips yielded positive cultures, for a mean duration, from surgery to sample collection, of 1.63 (0.5) days. None of the positive drain tip cultures developed clinical signs of infection and all knees were healed at discharge after a mean of 13.78 days (SD= 3.34; range= 8-18). None of the 7 (2.46%) cases who developed deep infections had positive drain tip cultures. A true positive value of 0 led to a positive predictive value of 0, a negative predictive value of 97.34%, sensitivity of 0% and specificity of 93.14. CONCLUSIONS: The diagnostic use of passive drain tip cultures to detect early infections after total knee replacement is therefore absolutely useless. PMID- 26152625 TI - Carpal tunnel release: transverse or longitudinal limited-incisions? AB - AIMS: Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy of the upper extremity. Surgical decompression through a limited open palmar incision is still the most widely used treatment. The aim of this study was to compare two different incision surgical techniques for carpal tunnel surgery. PATIENTS AND METHODS: In this retrospective study, 41 patient hands (transverse surgery) were compared with 55 controls (longitudinal surgery) using, as validated outcome instruments, the "Boston Carpal Tunnel Questionnaire" for postoperative effectiveness to measure symptoms, disability and health-related quality of life. The patients were monitored just before the CTS surgery and then 4 weeks and 3 months after surgery. RESULTS: Complications resulted few and comparable for both techniques. Results showed similar outcomes in both procedures regarding symptoms release and function, except for one month results where function was better for the transverse incision (p<0.01) which required reduced time, anyway. CONCLUSIONS: The transverse incision technique proved a suitable optimal solution for carpal tunnel release. This technique, therefore, induces to a better tolerated scar at short term follow up, compared to a standard palmar longitudinal incision. PMID- 26152626 TI - Randomized Controlled Trial Comparing Daycare and Overnight Stay Laparoscopic Cholecystectomy. AB - BACKGROUND: This present study sought to review the feasibility and patients' satisfaction of laparoscopic cholecystectomy to be perform as daycare procedure. MATERIAL AND METHODS: Sixty-two patients with symptomatic gallstones were recruited within a year. They were randomized into overnight stay and daycare groups. The outcomes and post-operative complications were analyzed. RESULTS: Fifty-eight patients were eligible for analysis and four patients were excluded because of conversion to open cholecystectomy. All patients in daycare group reported no fever but two patients in the overnight stay group complaint of post operative fever (p=0.150). The mean pain score using Visual Analogue Score (VAS) in daycare group was 2.93 but in the overnight stay was recorded as 3.59 (p=0.98). Five patients had post-operative nausea and vomiting (PONV) in daycare group compared to 2 patients in the overnight stay group (p=0.227). Patient's satisfaction were higher in the daycare group (p=0.160). All patients in daycare group were back at work within a week but in overnight stay, 11 patients had to stay off work for more than one week (p=0.01). CONCLUSIONS: Daycare laparoscopic cholecystectomy is safe and feasible. The satisfaction of daycare surgery is higher than overnight stay group. Patients' selection is an important aspect of its success. PMID- 26152627 TI - Diagnostic and therapeutic management of diabetic mastopathy: a case report. AB - Sclerosing lymphocytic lobulitis (SLL) is a benign breast lesion, better known as diabetic mastopathy (DMP), since it tipically occurs in diabetic patients. This very uncommon condition is strongly associated with type I diabetes mellitus. We report a case of a 61-year-old woman, with type II insulin-dependent diabetes mellitus, who presented mammography and ultrasonography images suspicious for breast carcinoma. As histopathology surprisingly demonstrated SLL and breast MRI showed benign characteristics, unnecessary surgery was avoided. The aim of this report is to underline that DMP is an uncommon clinicopathological entity which can clinically and radiologically mimic breast cancer but also that breast carcinoma may be hidden within these dense fibrotic lesions. In the light of cases reported in literature, breast MRI can be considered an essential tool in the diagnostic and therapeutic management of DMP. PMID- 26152628 TI - Gitelman's syndrome as a cause of poorly controlled hypokalemia. AB - Gitelman's syndrome is a rare autosomal recessive tubulopathy caused by a defect of the thiazide-sensitive sodium chloride co-transporter at the distal tubule, leading to hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria and low-to-normal blood pressure. Clinical features include transient periods of muscle weakness and tetany, dizziness, abdominal pains and constipation. Patients can also present with convulsions due to severe metabolic alkalosis or hypomagnesemia. Therefore, early recognition and treatment are important. Diagnosis of Gitelman's syndrome is usually made incidentally during adolescence or early adulthood based on clinical and biochemical findings. In this paper we present the case of a 23-year-old female patient referred to our nephrology department for severe hypokalemia. Complementary evaluation revealed hypokalemia, hypomagnesemia, metabolic alkalosis, increased chloride and sodium urinary excretion and reduced urinary calcium excretion with normal renal function. A diagnosis of Gitelman syndrome was established. Treatment included magnesium and potassium salts and potassium saving diuretics. In general, the long-term prognosis of Gitelman's syndrome is good if the patient adhere with the treatment. PMID- 26152629 TI - The protection of individuals affected with Specific Learning Disorders in the Italian Legislation. AB - Specific Learning Disorders (SLDs) affect specific abilities in individuals with an otherwise normal academic development. Among Italian School population, their reported prevalence is between 2.5% and 3.5%. Dysfunctions at the base of these disorders interfere with the normal acquisition process of reading, writing and/or mathematical abilities, leading to various degrees of adjustment difficulties in the affected individuals. The aim of this study was to assess the support that Italian Government offers to its citizens affected with SLDs, with a particular focus on assistance during the school-age years, particularly through the introduction of the Law 170/2010 and successive guidelines, supplementing the existing regulations to offer more efficient means and legal instruments aimed at achieving earlier diagnoses. PMID- 26152630 TI - Atopic dermatitis and alpha-chemokines. AB - Many studies have shown the involvement of interferon (IFN)gamma-inducible protein 10 (IP-10) and T-helper 1 (Th1) cytokines in Atopic Dermatitis (AD). IFN gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-18 are potent stimulators of the expression and secretion of IP-10 in cultured keratinocytes from AD patients. Apoptosis of keratinocytes, induced mainly by T cells and mediated by IFN-gamma, is the essential pathogenetic event in eczema formation. Enhanced IP-10, induced by IFN-gamma, and IFN-inducible T cell alpha chemoattractant (I-TAC) expression has been observed in lesional AD skin. It has been shown that keratinocytes undergoing apoptosis in acute eczematous lesions release chemokines that attract more T cells toward the epidermis, which may further augment the inflammation and keratinocyte apoptosis. Drugs used in the treatment of AD modulate IP-10. Antihistamines are widely used for the treatment of AD; it has been shown in human monocyte-derived dendritic cells (MoDCs) and autologous CD4+ T cells that antihistamines inhibited the production of IP-10 and?? monokine induced by IFN-gamma (MIG) expressions. It has been also shown that antimycotics and tacrolimus suppress the induced production of IP-10 in human keratinocytes. PMID- 26152631 TI - Hepatitis B virus infection and interferon-inducible protein-10. AB - Interferon (IFN)-inducible protein-10 (IP-10) is a proinflammatory chemokine, binding the chemokine (C-X-C motif) receptor 3 (CXCR3), which is found mainly on activated T cells and natural killer (NK) cells, and plays an important role in T helper (Th) 1 type inflammatory disorders (autoimmune, neoplastic, and infectious diseases). Concerning viral hepatitis, IP-10 appears to be involved on the pathogenesis of liver damage as well as on the extra-hepatic manifestations either protecting or promoting infection, depending on host immune status and genetic background. During chronic hepatitis B, IP-10 is specifically produced by hepatocytes in inflammatory areas. Here, IP-10 leads to recruitment of T cells, production of IFN-gamma by activated NK T cells, and then monokine induced by IFN gamma (MIG) and IP-10 secretion by parenchymal and non-parenchymal cells, with a final positive feedback, perpetuating the immune cascade. The increased levels of IP-10 and IP-10 mRNA in the peripheral blood of patients with cirrhosis are closely correlated with the load of HBV DNA in serum, and seem to play a key role in the progression of post-hepatitic cirrhosis. Higher pre-treatment IP-10 levels, and dynamic down-regulation, are associated with an increased probability of hepatitis B e antigen (HBeAg) loss after Peg-IFN therapy. Hepatitis B surface antigen (HBsAg) drop in patients treated with nucleos(t)ide analogues (NAs) is associated with higher baseline IP-10. PMID- 26152632 TI - Lymphocytic choriomeningitis and alpha-chemokines. AB - IP-10 and its receptor CXCR3 play an important role in lymphocytic choriomeningitis (LCM). During the course of LCM in mice not only cells of the immune system but also central nervous system (CNS) resident cells are actively involved in both the pro- and the counter-inflammatory immune circuits. A central role for IP-10 in regulating the accumulation of effector T cells at sites of CNS inflammation, with no apparent compensatory effect of other CXCR3 ligands, has been shown. The producers of IP-10 are mainly resident cells of the CNS, and astrocytes are the dominant expressors in the neural parenchyma, not microglial cells or recruited bone marrow-derived cell types. These results are consistent with a mode suggesting a bidirectional interplay between resident cells of the CNS and the recruited virus-specific T cells with astrocytes as active participants in the local antiviral host response. PMID- 26152633 TI - Human respiratory syncytial virus and Th1 chemokines. AB - The importance of the Type-1 helper (Th1) chemokines in RSV (respiratory syncytial virus) infection has been shown by several studies, in animal models, and in humans. The production of Th1 chemokines within the lower respiratory tract has been shown in patients with RSV bronchiolitis, particularly chemokine (C-X-C motif) ligand (CXCL)10/interferon-gamma-inducible protein 10 (IP-10), whose plasma levels were markedly elevated in acute infection. RSV fusion (F) or large (G) protein treatment of fully differentiated primary normal human bronchial epithelial cells induces apical secretion of IP-10 and other chemokines. Exposure to environmental tobacco smoke is associated with an increase in the frequency and severity of respiratory infections, including bronchiolitis, and inhibited RSV-induced Interferon (IFN)-alpha in plasmacytoid dendritic cells as well as the release of IP-10. Vitamin D in airway epithelium decreases RSV induction of NF-kappaB-driven genes such as IFN-beta and IP-10. These findings highlight the role for the IP-10: chemokine (C-X-C motif) receptor (CXCR)3 signaling axis in RSV-infection by recruiting virus-specific T cells into the lung and promoting viral clearance. PMID- 26152634 TI - An insight into the occurrence of suicides in jails of an Italian region. AB - The objective of this study is to explore the personal and environmental causes of suicides in jails of an Italian region, by evaluating the extent of the phenomenon, in order to devise strategies for prevention. The examined documentation deals with all cases of suicide among detainees in the 14 prisons of the region Lazio between 01/01/2008 and 31/12/2014. The factors considered for evaluation concerns the are socio-demographics (age, gender, nationality) as well as legal aspects, prison characteristics (type of crime, judicial state) and method used for the suicide. The results show that the method to commit suicide in prisoners of Lazio is hanged. Suicides occur especially in Italian prisoners. Most prison inmates commit suicide less than one year before the end of the detention period. Since the majority of risk factors for suicide are present before the subject enters prison, it is not easy to observe and check the prisoners once they are in jail. The evaluation of the prisoners should be done during the phase when they first enter the jail and not after the intervening variables associated with the detention have had their effects. This suggests that further studies are necessary to better understand the phenomenon and evaluate the possibility to introduce effective preventive measures. PMID- 26152635 TI - [Syncope: physiopathology, diagnosis and therapy]. AB - Nowadays, syncope still generates complicated challenges for clinicians for the alarm it arises in patients and, at the same time, for the multiple causes it has determined by. In almost one third of cases, syncope is neuromediated, in young subjects in vasovagal, whereas in elderly is often determinated by carotid sinus hypersensitivity. These two kinds of syncope have two completely different diagnostic approach. In some cases pace-maker implantation will be suggested to avoid new syncope episodes. In a 20% of cases, the underlying cause is arrhythmic, most of all bradiarrhythmia which is treated with pace-maker implantation. In a little number of cases, syncope is caused by ventricular arrhythmias, that require the implantation of a defibrillator device. In this review, we analyze in detail every cause of syncope with its diagnostic and therapeutic approach. PMID- 26152636 TI - [Literature review and state of the art of the Italian law on medically assisted reproduction]. AB - This article analyzes the current situation of medically assisted reproduction in Italy after the promulgation of Law 40 in 2004. This law is actually completely different from the origin version. The controversial points like reproduction for couples who bear genetic diseases, prohibition of heterologous fertilization, cryoconservation of the embryos, obligation to perform just one and contemporaneous implant of all the embryos produced, are today definitively erased. This new situation is due to the jurisprudence of the Italian Courts but especially to the changes introduced by the European Court of Human Rights and by the questions of constitutionality raised by some Italian Courts. After analysis of the legislation, the views of various authors are compared, and the weaknesses and strong points of the law are considered from the point of view of legal medicine, science and bioethics. After ten years of operation of this law Italy has returned to a situation that existed before the law. In fact the old law was only full of prohibitions. Now is possible to do heterologous fertilization and this article photographs the current situation of hospitals for assisted procreation in Italy. The work also comments on procreative tourism, a direct consequence of this law, and on the status of women, who must be the subject and not the object of the legislation. PMID- 26152637 TI - The complex interplay of Depression, Inflammation and Omega-3: state of the art and progresses in research. AB - Many epidemiological and preclinical studies have proven the potential benefit and critical role of omega-3 PUFAs in the development and management of depressive disorders. Depression may be the consequence of a complex interplay between cell-mediated-immune activation and inflammation evolving in neuroprogression. Associations between n-3 PUFAs, inflammation, oxidative stress and the risk of depression have been demonstrated and clinical and animal supplementation studies have shown the potential of PUFAs to decrease neurodegeneration and inflammation. Future research should focus on the dynamic interactions between the different cell signaling networks and oxidative and nitrosative stress pathways that cause depression. PMID- 26152638 TI - Vasculopathy in scleroderma. AB - Systemic sclerosis (SSc) is a multisystem connective tissue disorder featured by vascular injury and fibrosis of the skin and various internal organs with autoimmune background. Although the pathogenesis of SSc still remains elusive, it is generally accepted that initial vascular injury due to autoimmunity and/or environmental factors causes structural and functional abnormalities of vasculature which eventually result in the constitutive activation of fibroblasts in various organs. Structural alterations consist of destructive vasculopathy (loss of small vessels) and proliferative obliterative vasculopathy (occlusion of arterioles and small arteries with fibro-proliferative change) caused by impaired compensatory vasculogenesis and angiogenesis. Impaired function of SSc vasculature includes the altered expression of cell adhesion molecules predominantly inducing Th2 and Th17 cell infiltration, endothelial dysfunction primarily due to the low availability of nitric oxide, the activated endothelial to-mesenchymal transition leading to fibro-proliferative vascular change and tissue fibrosis, and the impaired coagulation/fibrinolysis system promoting the formation of intravascular fibrin deposits. Recent new insights into the therapeutic mechanisms of intravenous cyclophosphamide pulse and bosentan and the establishment of a new SSc animal model (Klf5 (+/-);Fli1 (+/-) mice) provide us useful clues to further understand the development of vascular alterations characteristic of SSc. This article overviewed the present understanding of the pathogenesis of SSc vasculopathy. PMID- 26152639 TI - The role of the acquired immune response in systemic sclerosis. AB - Profound alterations characterize the adaptive immune response in systemic sclerosis, and several layers of evidence support a prominent role exerted by immune cellular effectors and humoral mediators in the pathogenesis of this disease. These include (i) the presence of oligoclonal T cells in tissues undergoing fibrosis consistent with (auto)antigen-specific recruitment, (ii) the preferential expansion of polarized CD4+ and CD8+ T cells producing pro-fibrotic cytokines such as IL-4 and IL-13, (iii) the presence of increased number of cells producing mediators belonging to the IL-17 family, including IL-22, which may drive and participate in inflammatory pathways involving epithelial cells as well as fibroblasts, (iv) the deficient or redirected function of T regulatory cells favoring fibrosis, and (v) the enhanced expression of CD19 and CD21 on naive B cells, and the upregulation of co-stimulatory molecules in mature B cells, which together with the increased levels of B cell activating factor (BAFF) underlie the propensity to an exaggerated humoral response possibly favoring fibrogenesis. Despite all the progress made in understanding the features of the aberrant immune response in scleroderma, it remains unclear whether the activation of immune effector pathways ultimately drives the disease pathogenesis or rather represents a defective attempt to limit or even reverse excessive extracellular matrix deposition and progressive vasculopathy, the main hallmarks of this disease. PMID- 26152641 TI - Multi-echo susceptibility-weighted imaging and histology of open-field blast induced traumatic brain injury in a rat model. AB - Blast-induced traumatic brain injury is on the rise, predominantly as a result of the use of improvised explosive devices, resulting in undesirable neuropsychological dysfunctions, as demonstrated in both animals and humans. This study investigated the effect of open-field blast injury on the rat brain using multi-echo, susceptibility-weighted imaging (SWI). Multi-echo SWI provided phase maps with better signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), making it a sensitive technique for brain injury. Male Sprague-Dawley rats were subjected to a survivable blast of 180 kPa. The visibility of blood vessels of varying sizes improved with multi-echo SWI. Reduced signal intensity from major vessels post-blast indicates increased deoxyhaemoglobin. Relative cerebral blood flow was computed from filtered phase SWI images using inferred changes in oxygen saturation from major blood vessels. Cerebral blood flow decreased significantly at day 3 and day 5 post-blast compared with that pre-blast. This was substantiated by the upregulation of beta-amyloid precursor protein (beta-APP), a marker of ischaemia, in the neuronal perikaya of the cerebral cortex, as observed by immunofluorescence, and in the cortical tissue by western blot analysis. Our findings indicate the presence of brain ischaemia in post-blast acute phase of injury with possible recovery subsequently. Our results from cerebrovascular imaging, histology and staining provide an insight into the ischaemic state of the brain post-blast and may be useful for prognosis and outcome. PMID- 26152640 TI - Cytokines in the immunopathology of systemic sclerosis. AB - Cytokines and growth factors are key regulators of immune activation, vascular alteration and excessive production of extracellular matrix which are hallmark events in the pathogenesis of systemic sclerosis (SSc). They modulate cell-cell and cell-matrix interactions. In particular, cytokines play a central role in the immunopathogenesis of SSc on the basis of molecular pathways which are complex and not completely understood. The majority of cytokines that may be involved in SSc pathogenesis have effect upon or are derived from cells of the immune system, including both the innate and adaptive compartments. Novel therapies that block key mediators that drive the fibrotic response are being developed and appear as potential therapeutic tools in the treatment of SSc, highlighting the importance for an effective therapy targeted towards the molecular and cellular pathways. This article reviews cytokine biology in that context, with particular emphasis on immunopathology of the disease, therapeutic targeting and the way that current or emerging treatments for SSc might impact on cytokine biology. PMID- 26152643 TI - The shifting influence of drought and heat stress for crops in northeast Australia. AB - Characterization of drought environment types (ETs) has proven useful for breeding crops for drought-prone regions. Here, we consider how changes in climate and atmospheric carbon dioxide (CO2 ) concentrations will affect drought ET frequencies in sorghum and wheat systems of northeast Australia. We also modify APSIM (the Agricultural Production Systems Simulator) to incorporate extreme heat effects on grain number and weight, and then evaluate changes in the occurrence of heat-induced yield losses of more than 10%, as well as the co occurrence of drought and heat. More than six million simulations spanning representative locations, soil types, management systems, and 33 climate projections led to three key findings. First, the projected frequency of drought decreased slightly for most climate projections for both sorghum and wheat, but for different reasons. In sorghum, warming exacerbated drought stresses by raising the atmospheric vapor pressure deficit and reducing transpiration efficiency (TE), but an increase in TE due to elevated CO2 more than offset these effects. In wheat, warming reduced drought stress during spring by hastening development through winter and reducing exposure to terminal drought. Elevated CO2 increased TE but also raised radiation-use efficiency and overall growth rates and water use, thereby offsetting much of the drought reduction from warming. Second, adding explicit effects of heat on grain number and grain size often switched projected yield impacts from positive to negative. Finally, although average yield losses associated with drought will remain generally higher than that for heat stress for the next half century, the relative importance of heat is steadily growing. This trend, as well as the likely high degree of genetic variability in heat tolerance, suggests that more emphasis on heat tolerance is warranted in breeding programs. At the same time, work on drought tolerance should continue with an emphasis on drought that co-occurs with extreme heat. PMID- 26152642 TI - Neuronal SH-SY5Y cells use the C-dystrophin promoter coupled with exon 78 skipping and display multiple patterns of alternative splicing including two intronic insertion events. AB - Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by mutations in the dystrophin gene. One-third of DMD cases are complicated by mental retardation. Here, we used reverse transcription PCR to analyze the pattern of dystrophin transcripts in neuronal SH-SY5Y cells. Among the three alternative promoters/first exons at the 5'-end, only transcripts containing the brain cortex-specific C1 exon could be amplified. The C-transcript appeared as two products: a major product of the expected size and a minor larger product that contained the cryptic exon 1a between exons C1 and 2. At the 3'-end there was complete exon 78 skipping. Together, these findings indicate that SH-SY5Y cells have neuron-specific characteristics with regard to both promoter activation and alternative splicing. We also revealed partial skipping of exons 9 and 71. Four amplified products were obtained from a fragment covering exons 36 41: a strong expected product, two weak products lacking either exon 37 or exon 38, and a second strong larger product with a 568-bp insertion between exons 40 and 41. The inserted sequence matched the 3'-end of intron 40 perfectly. We concluded that a cryptic splice site was activated in SH-SY5Y cells to create the novel, unusually large, exon 41e (751 bp). In total, we identified seven alternative splicing events in neuronal SH-SY5Y cells, and calculated that 32 dystrophin transcripts could be produced. Our results may provide clues in the analysis of transcriptype-phenotype correlations as regards mental retardation in DMD. PMID- 26152645 TI - Erratum to: The Strength of Family Ties: Perceptions of Network Relationship Quality and Levels of C-Reactive Proteins in the North Texas Heart Study. PMID- 26152644 TI - Predicting Scheduling and Attending for an Oral Cancer Examination. AB - BACKGROUND: Oral and pharyngeal cancer is highly treatable if diagnosed early, yet late diagnosis is commonplace apparently because of delays in undergoing an oral cancer examination. PURPOSE: We explored predictors of scheduling and attending an oral cancer examination among a sample of Black and White men who were at high risk for oral cancer because they smoked. METHODS: During an in person interview, participants (N = 315) from rural Florida learned about oral and pharyngeal cancer, completed survey measures, and were offered a free examination in the next week. Later, participants received a follow-up phone call to explore why they did or did not attend their examination. RESULTS: Consistent with the notion that scheduling and attending an oral cancer exam represent distinct decisions, we found that the two outcomes had different predictors. Defensive avoidance and exam efficacy predicted scheduling an examination; exam efficacy and having coping resources, time, and transportation predicted attending the examination. Open-ended responses revealed that the dominant reasons participants offered for missing a scheduled examination were conflicting obligations, forgetting, and confusion or misunderstanding about the examination. CONCLUSIONS: The results suggest interventions to increase scheduling and attending an oral cancer examination. PMID- 26152646 TI - Estimated glomerular filtration rate (eGFR), 25(OH) D3, chronic kidney disease (CKD), the MYH9 (myosin heavy chain 9) gene in old and very elderly people. AB - It is known that the common physiological denominator of the ageing process is an attenuation of functional performance with respect to the situation of young people and adults. However, since the first cohort-based longitudinal studies, it has not been possible to establish a "linear" relationship between age and glomerular filtration in all cases. This does not mean that there is no physiological ageing process at all; in addition to those already elucidated, its mechanisms include cell senescence, podocyte dysfunction, a vitamin D deficiency, and homozygotic forms of the MYH9 gene. The aim of the present work was to analyse the prevalence of chronic kidney disease (CKD) and, where possible, the correlation between CKD, defined by an eGFR < 60 ml/min/1.73 m(2), plasma 25(OH)D3 levels and the MYH9 gene in a population of elderly and very elderly persons. These parameters have not been evaluated previously in populations of elderly and very elderly patients. It is concluded that a moderate decrease in the eGFR occurs with age. This does not imply the presence of CKD in elderly people, since in most individuals the reduced eGFR is not accompanied by anaemia, and no individuals show hypocalcaemia, hyperphosphataemia or a high Alb/Cr ratio. Here we observed a lower Hb level and an elevated Alb/Cr ratio in subjects heterozygotic for the MYH9 gene. This could be interpreted in the sense that the gene could exert some protective effect on renal function, whereas the heterozygotic form (allele A) of the MYH9 gene could be considered a very early marker, a new risk factor for the appearance of CKD, or a sign of renal frailty in elderly people. PMID- 26152647 TI - Risk of Second Primary Tumors After Childhood and Adolescent Ovarian Malignancies: A SEER Analysis (1973-2011). AB - STUDY OBJECTIVE: To calculate the incidence of second primary tumors (SPTs) in patients previously diagnosed with malignant ovarian tumors in childhood and adolescence. This is an area of interest given the high survival rate and, thus, the long disease-free period that these patients face. DESIGN AND PARTICIPANTS: We conducted a retrospective study following a cohort of patients between 1973 and 2011. Using the National Cancer Institute's Surveillance, Epidemiology and End-Result (SEER) database, we identified patients with an ovarian malignant tumor diagnosed at 19 years of age or younger. RESULTS: Of the 806 patients included in our study, 28 patients developed an SPT after the diagnosis of malignant ovarian tumor. This cohort had higher risk of solid tumors (standardized incidence ratio [SIR] 1.85, 95% CI 1.15 to 2.83) and lymphohematologic malignancies (SIR 5.28, 95% CI 2.12 to 10.88) compared with the general population. There is a higher incidence of lymphoma (SIR 4.25, 95% CI 1.16 to 10.89) and acute nonlymphocytic leukemia (SIR 19.65, 95% CI 4.05 to 57.42), following initial diagnosis of ovarian malignancy during childhood or adolescence. CONCLUSION: The association between ovarian malignancy during childhood or adolescence and lymphoma has not been previously described. Increased incidence of acute nonlymphocytic leukemia supports previous data, underlying the need for long-term follow-up and surveillance of these patients. PMID- 26152648 TI - Use of Dual Methods for Protection from Unintended Pregnancy and Sexually Transmitted Diseases in Adolescent African American Women. AB - STUDY OBJECTIVE: To characterize factors associated with dual method contraceptive use in a sample of adolescent women. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We conducted a cross-sectional survey of sexually active African American women aged 14-19 years who attended an urban Title X clinic in Georgia in 2012 (N = 350). Participants completed a computerized survey to assess contraceptive and condom use during the past 2 sexual encounters with their most recent partner. Dual method use was defined as use of a hormonal contraceptive or intrauterine device and a condom. We applied multinomial logistic regression, using generalized estimating equations, to examine the adjusted association between dual method use (vs use of no methods or less effective methods alone; eg, withdrawal) and select characteristics. RESULTS: Dual methods were used by 20.6% of participants at last sexual intercourse and 23.6% at next to last sexual intercourse. Having a previous sexually transmitted disease (adjusted odds ratio [aOR], 2.30; 95% confidence interval [CI], 1.26-4.18), negative attitude toward pregnancy (aOR, 2.25; 95% CI, 1.19-4.28), and a mother who gave birth as a teen (aOR, 2.34; 95% CI, 1.21-4.52) were associated with higher odds of dual method use. Having no health insurance (aOR, 0.39; 95% CI, 0.18-0.82), 4 or more lifetime sexual partners (aOR, 0.42; 95% CI, 0.22-0.78), sex at least weekly (aOR, 0.54; 95% CI, 0.29-0.99), and agreeing to monogamy with the most recent partner (aOR, 0.40; 95% CI, 0.16-0.96) were associated with decreased odds of dual method use. CONCLUSION: Dual method use was uncommon in our sample. Efforts to increase use of dual methods should address individual and relationship factors. PMID- 26152649 TI - Effects of Changes in Diabetes Pay-for-Performance Incentive Designs on Patient Risk Selection. AB - OBJECTIVE: Taiwan's National Health Insurance (NHI) Program implemented a Diabetes Pay-for-Performance Program (P4P) based on process-of-care measures in 2001. In late 2006, that P4P program was reformed to also include achievement of intermediate health outcomes. This study examined how the change in design affected patient risk selection. DESIGNS/STUDY POPULATIONS: Study populations were identified from a 2002 to 2003 period (Phase 1) and a 2007 to 2008 period (Phase 2), spanning pre- and postimplementation of reforms in the P4P incentive design. Phase 1 had 74,529 newly enrolled P4P patients and 215,572 non-P4P patients, and Phase 2 had 76,901 newly enrolled P4P patients and 299,573 non-P4P patients. Logistic regression models were used to estimate the effect of changes in design on P4P patient selection. PRINCIPAL FINDINGS: Patients with greater disease severity and comorbidity were more likely to be excluded from the P4P program in both phases. Furthermore, the additional financial incentive for patients' intermediate outcomes moderately worsened patient risk selection. CONCLUSIONS: Policy makers need to carefully monitor the care of the diabetes patients with more severe and complex disease statuses after the changes of P4P financial incentive design. PMID- 26152650 TI - Heat shock protein 90 inhibition: A potential double- or triple-edged sword in the treatment of mucous membrane pemphigoid. AB - Mucous membrane pemphigoid (MMP) is a subtype of autoimmune subepidermal blistering diseases characterized by autoantibodies to structural components of the hemidesmosome primarily affecting mucous membranes. Inflammation-related progressive scarring can lead to serious complications, including blindness, and the disease may be associated with malignancy. Conventional immunosuppressive treatment is often insufficiently effective and limited due to side effects, warranting new therapeutic options ideally targeting both inflammation and extensively recalcitrant cicatrization. Heat shock protein 90 (Hsp90) is a cell stress-inducible chaperone required for the function of a large number of client proteins, and its pharmacological inhibition has proven to be effective and relatively safe in patients with cancer. Recent observations also suggest a promising role of Hsp90 as drug target in preclinical in vivo murine models of autoimmune diseases such as subepidermal bullous and fibrotic autoimmune disorders comprising epidermolysis bullosa acquisita and systemic sclerosis, respectively, which exhibit some pathophysiological features reminiscent of MMP. This article thus hypothesizes that Hsp90 blockade could represent a double-edged sword in MMP treatment by targeting pathogenic factors of inflammatory blister and fibrosis formation. Moreover, Hsp90 inhibitors could even be proclaimed as a triple-edged sword in case of an underlying malignancy. Future studies investigating the role of Hsp90 in MMP are needed to clarify whether Hsp90 inhibition could become a novel treatment approach for patients with this potentially devastating disease. PMID- 26152651 TI - Sorafenib in the treatment of thyroid cancer. AB - Sorafenib has been evaluated in several Phase II and III studies in patients with locally advanced/metastatic radioactive iodine-refractory differentiated thyroid carcinomas (DTCs), reporting partial responses, stabilization of the disease and improvement of progression-free survival. Best responses were observed in lung metastases and minimal responses in bone lesions. On the basis of these studies, sorafenib was approved for the treatment of metastatic DTC in November 2013. Few studies suggested that reduction of thyroglobulin levels, or of average standardized uptake value at the fluorodeoxyglucose-PET, could be helpful for the identification of responding patients; but further studies are needed to confirm these results. Tumor genetic marker levels did not have any prognostic or predictive role in DTC patients.The most common adverse events observed included skin toxicity and gastrointestinal and constitutional symptoms. Encouraging results have also been observed in patients with medullary thyroid cancer. Many studies are ongoing to evaluate the long-term efficacy and tolerability of sorafenib in DTC patients. PMID- 26152652 TI - AN ASSESSMENT OF THE COURT'S ROLE IN THE WITHDRAWAL OF CLINICALLY ASSISTED NUTRITION AND HYDRATION FROM PATIENTS IN THE PERMANENT VEGETATIVE STATE. AB - In this article, we reassess the court's role in the withdrawal of clinically assisted nutrition and hydration from patients in the permanent vegetative state (PVS), focussing on cases where health-care teams and families agree that such is in the patient's best interest. As well as including a doctrinal analysis, the reassessment draws on empirical data from the families of patients with prolonged disorders of consciousness, on economic data about the costs of the declaratory relief process to the National Health Service (NHS), and on comparative legal data about the comparable procedural requirements in other jurisdictions. We show that, following the decision in the Bland case, the role of the Court of Protection is now restricted to the direct supervision of the PVS diagnosis as a matter of proof. We argue that this is an inappropriate role for the court, and one that sits in some tension with the best interests of patients. The blanket requirement of declaratory relief for all cases is economically expensive for the NHS and thus deprives other NHS patients from health care. We demonstrate that many of the ancillary benefits currently offered by declaratory relief could be achieved by other means. Ultimately, we suggest that reform to the declaratory relief requirement is called for. PMID- 26152653 TI - A Long Night in the Emergency Department during the Baltimore, Maryland (USA) Riots. PMID- 26152654 TI - Multiple repair sequences in everyday conversations involving people with Parkinson's disease. AB - BACKGROUND: Features of dysarthria associated with Parkinson's disease (PD), such as low volume, variable rate of speech and increased pauses, impact speaker intelligibility. Those affected report restricted interactional participation, although this area is under explored. AIMS: To examine naturally occurring instances of problems with intelligibility that resulted in multiple attempts at repair in order to consider repair initiation strategies that might restrict or enhance participation. METHODS & PROCEDURES: Thirteen people with PD (PwPD) video recorded over 10 h of informal conversation data in their home setting involving familiar conversation partners (CPs). Using a conversation analytic (CA) approach, and drawing on an existing typology of repair initiators (RIs) for everyday talk-in-interaction and their relative power to locate a turn's repairable element, the design and ordering of RIs used by CPs was addressed, alongside their local consequences. OUTCOMES & RESULTS: CPs tended to increase the specificity of their RIs in line with the existing typology, progressing from open class forms (e.g. 'mm?') to more specific forms (e.g. questions/partial repeats). Repeated open class repair initiators (OCRIs) were used where PD speakers' self-repair attempts provided limited information. Sometimes, however, specificity was increased too soon, before enough syntactic knowledge was gleaned, which resulted in an extended repair sequence. Where one OCRI followed another, the second always took a different form: lexically or in terms of prosodic/non-verbal features. RI forms not described in the existing typology were also identified, such as 'prompts to modify speech' (e.g. 'Speak louder') and repeating/rephrasing the original first pair part (e.g. question), and their effectiveness examined. CONCLUSIONS & IMPLICATIONS: First steps are presented towards the design of a communication intervention promoting the efficient resolution of repair to moderate social withdrawal and increase participation for this client group. Future research will need to explore the feasibility and acceptability of such a resource. PMID- 26152655 TI - The role of radiation therapy in the management of sialorrhea: A systematic review. AB - PURPOSE: Up to 80% of patients with Parkinson disease and 30% of patients with amyotrophic lateral sclerosis (ALS) suffer from sialorrhea. Patients who fail medical and surgical therapy should be considered for external beam radiation therapy (EBRT). In this study, we conduct a systematic review to determine the dose and techniques used that result in greatest efficacy and lowest toxicity for the administration of EBRT in patients with Parkinson disease or ALS-associated sialorrhea. METHODS AND MATERIALS: This review included 216 patients from four prospective and six retrospective studies published from 1998 to 2014, with ALS or Parkinson disease who were treated with electron or photon EBRT for sialorrhea. RESULTS: A total of 216 patients were treated with EBRT from 10 studies. The indication for EBRT was failure of alternative medical treatment in all ALS patients. For patients with Parkinson disease, EBRT was the primary mode of treatment in 68% of cases. Overall, 176 (81%) of 216 patients treated with EBRT for sialorrhea reported symptomatic improvement from baseline. The most common target was the inferior two-thirds of the bilateral parotid glands and the entire bilateral submandibular glands. The total number of patients who experienced short-term toxicity was 86 of 216 patients (40%). The total number of patients who experienced long-term toxicity was 24 of 207 (12%). CONCLUSIONS: EBRT is an effective treatment for sialorrhea in patients suffering from ALS or Parkinson disease. Treatment to the bilateral submandibular glands and caudal parotid glands is the most common field arrangement. PMID- 26152656 TI - Detection of BRAF c.1799T > A (p.V600E) mutation using residual routine fine needle aspiration specimens of papillary thyroid carcinoma. AB - BACKGROUND: BRAF p.V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC) and has been used as a diagnostic and prognostic marker in PTC. The aim of this study was to investigate the utility of preoperative BRAF p.V600E mutation analysis as an adjunctive diagnostic and prognostic tool to routine fine-needle aspiration (FNA). METHODS: Specimens were collected from thyroid nodules by FNA. Cytology diagnosis and BRAF p.V600E testing were performed on these specimens. Molecular and cytological results were correlated with histology outcomes. RESULTS: A total of 195 patients with thyroid nodules were enrolled, including 25 benign lesions and 170 PTCs. BRAF p.V600E testing was successfully performed in all specimens. The combination of BRAF p.V600E testing and cytology improved the sensitivity of cytology from 70% to 85.3% (P = 0.001). This significant increase in sensitivity was due to the detection of PTC by BRAF p.V600E testing in the nodules with atypical or suspicious PTC cytology results. Patients with BRAF p.V600E-positive tumors were significantly older than those who did not harbor mutations (45.6 years vs. 39.8 years, P = 0.002). No correlations between BRAF p.V600E mutation and other clinical-pathology parameters were observed. CONCLUSIONS: Detection of BRAF p.V600E mutation can be successfully carried out using residual liquid-based materials. It can be performed as a diagnostic tool to supplement traditional thyroid FNA, especially in cases with atypical or suspicious PTC. However, the role of BRAF p.V600E in guidance of the extent of thyroidectomy and nodal clearance requires further study. PMID- 26152658 TI - Prevalence of antibiotic use: a comparison across various European health care data sources. AB - PURPOSE: There is widespread concern about increases in antibiotic use, but comparative data from different European countries on rates of use are lacking. This study was designed to measure and understand the variation in antibiotic utilization across five European countries. METHODS: Seven European healthcare databases with access to primary care data from Denmark, Germany, the Netherlands, Spain and the UK were used to measure and compare the point and 1 year-period prevalence of antibiotic use between 2004 and 2009. Descriptive analyses were stratified by gender, age and type of antibiotic. Separate analyses were performed to measure the most common underlying indications leading to the prescription of an antibiotic. RESULTS: The average yearly period prevalence of antibiotic use varied from 15 (Netherlands) to 30 (Spain) users per 100 patients. A higher prevalence of antibiotic use by female patients, the very young (0-9 years) and old (80+ years), was observed in all databases. The lowest point prevalence was recorded in June and September and ranged from 0.51 (Netherlands) to 1.47 (UK) per 100 patients per day. Twelve percent (Netherlands) to forty-nine (Spain) percent of all users were diagnosed with a respiratory tract infection, and the most common type of antibiotic prescribed were penicillin. CONCLUSION: Using identical methodology in seven EU databases to assess antibiotic use allowed us to compare drug usage patterns across Europe. Our results contribute quantitatively to the true understanding of similarities and differences in the use of antibiotic agents in different EU countries. PMID- 26152659 TI - Extrahepatic arteries of the human liver - anatomical variants and surgical relevancies. AB - The purpose of our study was to investigate the anatomical variations of the extrahepatic arterial structures of the liver with particular attention to rare variations and their potential impact on liver surgery. A total of 50 human abdominal organ complexes were used to prepare corrosion casts. A multicomponent resin mixture was injected into the abdominal aorta. The portal vein was injected with a different colored resin in 16 cases. Digestion of soft tissues was achieved using cc. KOH solution at 60-65 degrees C. Extrahepatic arterial variations were classified according to Michels. All specimens underwent 3D volumetric CT reconstruction. Normal anatomy was seen in 42% of cases, and variants were seen in the other 58%. No Michels type VI or X variations were present; however, in 18% of cases the extrahepatic arterial anatomy did not fit into Michels' classification. We report four new extrahepatic arterial variations. In contrast to the available data, normal anatomy was found much less frequently, whereas the prevalence of unclassified arterial variations was higher. We detected four previously unknown variations. Our data may contribute to the reduction of complications during surgical and radiological interventions in the upper abdomen. PMID- 26152660 TI - The role of viral co-infection in HIV-associated non-AIDS-related cancers. AB - HIV-infected individuals are at increased risk for most types of cancer, including those typically classified as non-AIDS-defining cancers (NADCs). This increased risk is likely multifactorial, but a prominent risk factor for the increased rate of some cancers is co-infection with oncogenic viruses. Anal cancer, hepatocellular carcinoma, and Hodgkin lymphoma are three of the most common NADCs, and they are associated with co-infection with human papillomavirus, hepatitis B and C, and Epstein Barr virus, respectively. This review will examine the epidemiology, pathogenesis, and future trends around these virally associated NADCs frequently found in HIV-infected individuals. PMID- 26152661 TI - Acute HCV in HIV-infected MSM: modes of acquisition, liver fibrosis, and treatment. AB - Hepatitis C virus (HCV) is not considered to be efficiently transmitted sexually, but since the early 2000s, HCV infection of HIV-infected men who have sex with men has emerged as an epidemic worldwide. In this review, we discuss the epidemiology of sexually transmitted acute HCV, the growing body of literature regarding risk factors for acquisition, and possible mechanisms of transmission. We also discuss the progression of liver disease in these men and the advances in therapy of acute HCV with interferon-free regimens and put forth our current approach of evaluating and treating these men in New York City. PMID- 26152662 TI - IL-7 receptor deletion ameliorates diet-induced obesity and insulin resistance in mice. AB - AIM/HYPOTHESIS: Obesity-induced inflammation plays an important role in the development of insulin resistance and type 2 diabetes. Recent studies have demonstrated that adiposity can be improved by ablating certain inflammatory signalling pathways. Although the IL-7 receptor (IL-7R) is mostly known as a key regulator of T lymphocyte development and homeostasis, its role in obesity and metabolic diseases is unknown. Because IL-7 is markedly increased in the serum of obese individuals and IL-7R (also known as IL7R) is overexpressed in white adipose tissue (WAT) in obesity, we studied the metabolic consequences of genetic Il-7r ablation in mice. METHODS: Age-matched Il-7r-deficient (Il-7r KO) and wild type (WT) littermates were fed a standard chow or high-fat diet (HFD) for 14 weeks. Their serum metabolic variables were measured. The expression of genes and proteins related to insulin resistance and inflammation was evaluated in WAT. RESULTS: We demonstrated that Il-7r KO mice exhibited significantly reduced body weight gain and visceral adiposity compared with WT controls on both chow and HFD. The expression of signalling molecules involved in adipogenesis was reduced in the WAT of Il-7r KO mice. We also found that Il-7r KO mice had significantly enhanced glucose homeostasis and insulin sensitivity. Consistent with an improved metabolic phenotype, proinflammatory cytokine production and macrophage infiltration was attenuated in the WAT of Il-7r KO mice. CONCLUSIONS/INTERPRETATION: The IL-7R plays an important role in the induction of HFD-induced adipogenesis and insulin resistance in mice. PMID- 26152663 TI - Polish experience of lenalidomide in the treatment of lower risk myelodysplastic syndrome with isolated del(5q). AB - BACKGROUND: Lenalidomide has been approved for the treatment of lower-risk myelodysplastic syndrome (MDS) with 5q deletion (del(5q)). We present for the first time a retrospective analysis of low-risk MDS with isolated del5q treated with lenalidomide, outside the clinical trials. METHODS: 36 red blood cell (RBC) transfusion-dependent patients have been included in the study. Patients received lenalidomide 10 mg/day on days 1-21 of 28-day cycles. RESULTS: 91.7 % of patients responded to lenalidomide treatment: 72.2 % achieved erythroid response, 19.4 % achieved minor erythroid response and 8.4 % of patients did not respond to treatment. Response depended on number of previous treatment lines (p = 0.0101), International Prognostic System Score (IPSS; p = 0.0067) and RBC transfusion frequency (p = 0.0139). Median duration of response was 16 months (range 6-60 months). Treatment was well tolerated. We observed hematological toxicity (grade 3 and 4): neutropenia in 16 (44.4 %) patients and thrombocytopenia in 9 (25 %) patients. Two patients (5.5 %) progressed to high-risk MDS and two subsequent progressed to acute myeloid leukemia. A Kaplan-Meier estimate for overall survival at 5 years in the study group was 79.0 +/- 8.8 %. CONCLUSIONS: Lenalidomide in this group of patients was beneficial for the treatment of RBC transfusion-dependency with well-known safety profile. PMID- 26152664 TI - Individual Differences in Childhood Behavior Disorders Associated With Epigenetic Modulation of the Cortisol Receptor Gene. AB - Behavioral/emotional difficulties in children are the first sign of mental health problems. These problems are however, heterogeneous. A domain that may identify homogenous subgroups is hypothalamic-pituitary-adrenal function. This study tested whether epigenetic regulation of glucocorticoid receptor gene could explain the co-occurrence of anxiety problems in children with behavior problems. Four- to 16-year-old clinically referred children (N = 241) were measured for psychiatric symptoms, methylation of target CpG sites in blood or saliva, and morning cortisol levels in those who gave blood. Increased methylation of promoter 1F CpG sites was associated with higher vulnerability to co-occurring internalizing symptoms and morning cortisol. The results support increasing optimism that epigenetic regulation of key neuroendocrine systems might help explain hitherto unfathomable individual differences in susceptibility to psychiatric symptom profiles. PMID- 26152666 TI - The results of surgical treatment for pronation deformities of the forearm in cerebral palsy after a mean follow-up of 17.5 years. AB - AIM: This study evaluates the effects of three surgical procedures in the treatment of pronation deformities of the forearm in cerebral palsy patients; namely the transposition of pronator teres to extensor carpi radialis brevis muscle; and rerouting of the pronator teres muscle with or without pronator quadratus muscle myotomy. METHODS: Sixty-one patients, 48 male/13 female, with a mean age of 17 years (5-41 years) were treated between 1971 and 2011. Pronator teres transposition was performed in 10, pronator rerouting in 35, and pronator rereouting with pronator quadratus myotomy in 16 patients. Ranges of motion, and assessments using the Quick Dash, Mayo Scoring, and Functional Classification system of upper extremity, were made before and after surgery. Mean follow-up was 17.5 years (3-41 years). RESULTS: All three procedures led to significantly improved ranges of motion and upper limb function, with good/excellent results in 80 % of patients. Mean active supination improved from 10 degrees (0-60 degrees ) to 85 degrees (30-90 degrees ) (p < 0.001). There were significant improvements in Functional Classification system for the upper extremity scores (p < 0.003), Mean Quick Dash Scores improved from 58.41 (38.63-79.54) to 44.59 (27.27-68.18), and mean MEPS improved from 68 (30-85) to 84 (60-100) following surgery. All three techniques had statistically improved MEPS following surgery (p < 0.001); only the pronator teres muscle rerouting with pronator quadratus myotomy showed an improved Functional Classification system for the upper extremity score (p < 0.05); and only the pronator teres rerouting procedure showed an improved Quick Dash score (p < 0.05). There were no statistically significant differences in outcomes between different ages groups, and no significant differences between isolated pronator teres muscle rerouting were compared with those undergoing simultaneous treatment of carpal flexion and thumb adduction deformities (p > 0.05). CONCLUSION: Surgery is very effective in the management of pronation deformities of the forearm in patients with cerebral palsy. Isolated pronator teres rerouting is probably the most effective and simple technique. Adjunctive pronator quadratus myotomy does not lead to an improvement in the results and requires an additional surgical approach. There should be no age restriction to surgery, as all age groups appear to benefit from similar improvements in range of motion and upper limb function. PMID- 26152667 TI - Working While Rehabbing. PMID- 26152665 TI - Characterization of microbial community structure during continuous anaerobic digestion of straw and cow manure. AB - Responses of bacterial and archaeal communities to the addition of straw during anaerobic digestion of manure at different temperatures (37 degrees C, 44 degrees C and 52 degrees C) were investigated using five laboratory-scale semi-continuous stirred tank reactors. The results revealed that including straw as co-substrate decreased the species richness for bacteria, whereas increasing the operating temperature decreased the species richness for both archaea and bacteria, and also the evenness of the bacteria. Taxonomic classifications of the archaeal community showed that Methanobrevibacter dominated in the manure samples, while Methanosarcina dominated in all digesters regardless of substrate. Increase of the operating temperature to 52 degrees C led to increased relative abundance of Methanoculleus and Methanobacterium. Among the bacteria, the phyla Firmicutes and Bacteroidetes dominated within all samples. Compared with manure itself, digestion of manure resulted in a higher abundance of an uncultured class WWE1 and lower abundance of Bacilli. Adding straw to the digesters increased the level of Bacteroidia, while increasing the operating temperature decreased the level of this class and instead increased the relative abundance of an uncultured genus affiliated to order MBA08 (Clostridia). A considerable fraction of bacterial sequences could not be allocated to genus level, indicating that novel phylotypes are resident in these communities. PMID- 26152668 TI - Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia. AB - Schizophrenia is characterized by dysfunction in basic auditory processing, as well as higher-order operations of verbal learning and executive functions. We investigated whether targeted cognitive training of auditory processing improves neural responses to speech stimuli, and how these changes relate to higher-order cognitive functions. Patients with schizophrenia performed an auditory syllable identification task during magnetoencephalography before and after 50 hours of either targeted cognitive training or a computer games control. Healthy comparison subjects were assessed at baseline and after a 10 week no-contact interval. Prior to training, patients (N = 34) showed reduced M100 response in primary auditory cortex relative to healthy participants (N = 13). At reassessment, only the targeted cognitive training patient group (N = 18) exhibited increased M100 responses. Additionally, this group showed increased induced high gamma band activity within left dorsolateral prefrontal cortex immediately after stimulus presentation, and later in bilateral temporal cortices. Training-related changes in neural activity correlated with changes in executive function scores but not verbal learning and memory. These data suggest that computerized cognitive training that targets auditory and verbal learning operations enhances both sensory responses in auditory cortex as well as engagement of prefrontal regions, as indexed during an auditory processing task with low demands on working memory. This neural circuit enhancement is in turn associated with better executive function but not verbal memory. PMID- 26152669 TI - Formal Speech-Language Screening Not Shown to Help Children. PMID- 26152670 TI - Screening for Speech and Language Delay and Disorders in Children Aged 5 Years or Younger: US Preventive Services Task Force Recommendation Statement. AB - BACKGROUND: This report is an update of the US Preventive Services Task Force (USPSTF) 2006 recommendation on screening for speech and language delay in preschool-aged children. METHODS: The USPSTF reviewed the evidence on screening for speech and language delay and disorders in children aged 5 years or younger, including the accuracy of screening in primary care settings, the role of surveillance by primary care clinicians, whether screening and interventions lead to improved outcomes, and the potential harms associated with screening and interventions. POPULATION: This recommendation applies to asymptomatic children aged 5 years or younger whose parents or clinicians do not have specific concerns about their speech, language, hearing, or development. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for speech and language delay and disorders in children aged 5 years or younger (I statement). PMID- 26152671 TI - Screening for Speech and Language Delay in Children 5 Years Old and Younger: A Systematic Review. AB - BACKGROUND AND OBJECTIVES: No recommendation exists for or against routine use of brief, formal screening instruments in primary care to detect speech and language delay in children through 5 years of age. This review aimed to update the evidence on screening and treating children for speech and language since the 2006 US Preventive Services Task Force systematic review. METHODS: Medline, the Cochrane Library, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and reference lists. We included studies reporting diagnostic accuracy of screening tools and randomized controlled trials reporting benefits and harms of treatment of speech and language. Two independent reviewers extracted data, checked accuracy, and assigned quality ratings using predefined criteria. RESULTS: We found no evidence for the impact of screening on speech and language outcomes. In 23 studies evaluating the accuracy of screening tools, sensitivity ranged between 50% and 94%, and specificity ranged between 45% and 96%. Twelve treatment studies improved various outcomes in language, articulation, and stuttering; little evidence emerged for interventions improving other outcomes or for adverse effects of treatment. Risk factors associated with speech and language delay were male gender, family history, and low parental education. A limitation of this review is the lack of well-designed, well conducted studies addressing whether screening for speech and language delay or disorders improves outcomes. CONCLUSIONS: Several screening tools can accurately identify children for diagnostic evaluations and interventions, but evidence is inadequate regarding applicability in primary care settings. Some treatments for young children identified with speech and language delays and disorders may be effective. PMID- 26152672 TI - Child health - leading the way in integrated care. PMID- 26152673 TI - Diagnostic accuracy of cardiothoracic ratio on admission chest radiography to detect left or right ventricular systolic dysfunction: a retrospective study. AB - OBJECTIVES: To determine the diagnostic accuracy of the cardiothoracic ratio on postero-anterior or antero-posterior chest radiographs in predicting left ventricular or right ventricular dysfunction on echocardiography in an inpatient population. DESIGN: Retrospective study. SETTING: Two secondary care hospitals in the United Kingdom. PARTICIPANTS: Four hundred consecutive inpatient echocardiograms were screened for inclusion along with chest radiographs (both postero-anterior and antero-posterior). The cardiothoracic ratio was calculated from chest radiographs along with quantitative and qualitative measures of left ventricular or right ventricular dysfunction on echocardiography. MAIN OUTCOME MEASURES: Sensitivity and specificity of cardiothoracic ratio across a range of values to detect moderate/severe left ventricular and/or right ventricular dysfunction on echocardiography. RESULTS: Overall, 272 records met inclusion criteria. The prevalence of left ventricular/right ventricular dysfunction on echocardiography was 26% in an inpatient population with high clinical suspicion of cardiac disease referred for echocardiography. Over a range of cardiothoracic ratio values on postero-anterior films, a value of >0.55 yielded the best sensitivity (62.5%) and specificity (76.5%) for diagnosing left ventricular/right ventricular impairment (positive likelihood ratio 2.56), with a positive predictive value of 29.5%. Cardiothoracic ratio on antero-posterior film was not predictive of left ventricular/right ventricular impairment on echocardiography. CONCLUSIONS: In conclusion, in the context of an acute admission, cardiothoracic ratio measured on postero-anterior or antero-posterior films has limited value in detecting moderate left ventricular and/or right ventricular systolic dysfunction. Previously established absolute values may be unreliable by modern standards. PMID- 26152674 TI - Revisiting an ancient treatment for transphincteric fistula-in-ano 'There is nothing new under the sun' Ecclesiastes 1v9. AB - OBJECTIVE: The history of treatments for fistula-in-ano can be traced back to ancient times. Current treatment of transphincteric fistulae is controversial, with many options available. We reviewed the history of treatment using cutting setons and present our series of transphincteric fistulae in the light of the series in the literature. DESIGN: Literature review and case series. SETTING: Hospital based coloproctology service PARTICIPANTS: 140 consecutive patients presenting with fistula-in-ano were included. MAIN OUTCOME MEASURES: The literature pertaining to treatment of transphincteric fistula was reviewed, along with the outcome of various treatment methods for this condition. Data were collected for 140 consecutive patients presenting with fistula- in-ano were assessed for fistula healing, recurrence and complications. RESULTS: A total of 140 consecutive patients with fistula-in-ano were identified, of which 111 were cryptoglandular (79.3%). Eighty-one of these 111 were transphincteric (73.0%). At a median follow-up of 35 months (range, 2-83 months), 70 transphincteric fistulae had healed (86.4%), 10 were still undergoing treatment (12.3%) and one patient was lost to follow-up prior to treatment (1.2%). Two patients in this group required a stoma (2.5%), six patients developed recurrence (7.4%); three 'true' recurrences (3.7%). One (1.2%) developed a chronic fissure. There were no reported cases of incontinence. CONCLUSIONS: The management of transphincteric fistula-in-ano is complex and controversial, for which no clear surgical procedure has gained acceptance as the gold standard. This study demonstrates that transphincteric fistulae can be successfully treated using cutting setons. A high healing rate (86.4%), low recurrence rate (7.4%) and a low complication rate (3.7%) are shown, which compares favourably with published rates over a long follow-up. PMID- 26152675 TI - Ethnic variations in morbidity and mortality from lower respiratory tract infections: a retrospective cohort study. AB - OBJECTIVE: There is evidence of substantial ethnic variations in asthma morbidity and the risk of hospitalisation, but the picture in relation to lower respiratory tract infections is unclear. We carried out an observational study to identify ethnic group differences for lower respiratory tract infections. DESIGN: A retrospective, cohort study. SETTING: Scotland. PARTICIPANTS: 4.65 million people on whom information was available from the 2001 census, followed from May 2001 to April 2010. MAIN OUTCOME MEASURES: Hospitalisations and deaths (any time following first hospitalisation) from lower respiratory tract infections, adjusted risk ratios and hazard ratios by ethnicity and sex were calculated. We multiplied ratios and confidence intervals by 100, so the reference Scottish White population's risk ratio and hazard ratio was 100. RESULTS: Among men, adjusted risk ratios for lower respiratory tract infection hospitalisation were lower in Other White British (80, 95% confidence interval 73-86) and Chinese (69, 95% confidence interval 56-84) populations and higher in Pakistani groups (152, 95% confidence interval 136-169). In women, results were mostly similar to those in men (e.g. Chinese 68, 95% confidence interval 56-82), although higher adjusted risk ratios were found among women of the Other South Asians group (145, 95% confidence interval 120-175). Survival (adjusted hazard ratio) following lower respiratory tract infection for Pakistani men (54, 95% confidence interval 39-74) and women (31, 95% confidence interval 18-53) was better than the reference population. CONCLUSIONS: Substantial differences in the rates of lower respiratory tract infections amongst different ethnic groups in Scotland were found. Pakistani men and women had particularly high rates of lower respiratory tract infection hospitalisation. The reasons behind the high rates of lower respiratory tract infection in the Pakistani community are now required. PMID- 26152676 TI - Hormonal contraceptives and asthma in women of reproductive age: analysis of data from serial national Scottish Health Surveys. AB - OBJECTIVES: Sex steroid hormones may explain known gender-related variations in asthma prevalence and clinical manifestation. We investigated the relationship between use of hormonal contraceptives and asthma in women, and assessed evidence of biological interaction between use of hormonal contraceptives and body mass index in this relationship. DESIGN: Population-based analysis using data from serial (i.e. 2003, 2008 and 2010) Scottish Health Surveys. SETTING: Random samples of the Scottish general population. PARTICIPANTS: A total of 3257 non pregnant, 16-45-year-old women. EXPOSURE: Current use of hormonal contraceptives. MAIN OUTCOME MEASURES: Self-reported current physician-diagnosed asthma, current wheezing symptoms, wheezing attacks and treatment for asthma or wheeze. RESULTS: Women comprising 30.9% (95% confidence interval 29.3-32.5) were currently using any hormonal contraceptive and current physician-diagnosed asthma was present in 6.5% (95% confidence interval 5.7-7.4). Use of any hormonal contraceptive was associated with reduced risk of current physician-diagnosed asthma (odds ratio 0.68; 95% confidence interval 0.47-0.98) and receiving >=3 asthma care episodes (odds ratio 0.45; 95% confidence interval 0.25-0.82), but the evidence was equivocal for wheezing attacks. Use of hormonal contraceptives among overweight or obese women was non-statistically significantly associated with asthma, but there was 42-135% increased risk in overweight and obese non-contraceptive using women. CONCLUSIONS: Use of hormonal contraceptives may reduce asthma exacerbations and number of care episodes. Overweight and obese non-contraceptive using women may be at increased risk of asthma. Prospective studies are now needed to confirm these findings. Both oestrogen and progesterone may stimulate smooth airway muscle function and inhibit the activities of TH2 responses. Future studies should investigate these underlying mechanisms. PMID- 26152677 TI - Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review. AB - OBJECTIVES: We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials. PARTICIPANTS: Men and women from 30 to 74 years of age. SETTING: Randomised trials on cancer screening. DESIGN: For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death. MAIN OUTCOME MEASURES: Relative risk of cancer death. RESULTS: In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening. CONCLUSIONS: The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups. PMID- 26152679 TI - What Is in a Name? How Biomedical Language May Derail Patient Understanding of Hypertension. AB - Despite major advances in treating hypertension, >50% of all individuals diagnosed with the condition remain in poor control. A fundamental issue may be that patients may not fully understand the meaning of the term hypertension or its cause, leading to poor adherence to medications and limiting other effective self-management behaviors. We posit that the word hypertension itself may contribute to these misunderstandings, particularly in regards to the role of stress in causing hypertension, which thus suggests stress management as a primary strategy for control. The word hypertension is often interpreted by patients to mean too much tension. In conjunction with cultural framings of stress causing high blood pressure, many patients turn to stress management to control their hypertension. The word hypertension can thus cause patients to think of it as more of a psychological than physiological condition, thus discounting the value of antihypertensive medications and interfering with medication adherence. We therefore suggest that clinicians reconsider the use of the term hypertension and the ways in which they explain the condition to patients. Reorienting the language to the more patient-centered term of high blood pressure may help patients better understand the condition and to more readily embrace the available efficacious therapies. PMID- 26152678 TI - The association of copy number variation and percent mammographic density. AB - BACKGROUND: Percent mammographic density (PD) estimates the proportion of stromal, fat, and epithelial breast tissues on the mammogram image. Adjusted for age and body mass index (BMI), PD is one of the strongest risk factors for breast cancer. Inherited factors are hypothesized to explain between 30 and 60% of the variance in this trait. However, previously identified common genetic variants account for less than 6% of the variance in PD, leaving much of the genetic contribution to this trait unexplained. We performed the first study to examine whether germline copy number variation (CNV) are associated with PD. Two genome wide association studies (GWAS) of percent density conducted on the Illumina 660W Quad were used to identify and replicate the association between candidate CNVs and PD: the Minnesota Breast Cancer Family Study (MBCFS) and controls from the Mayo Venous Thromboembolism (Mayo VTE) Case-Control Study, with 585 and 328 women, respectively. Linear models were utilized to examine the association of each probe with PD, adjusted for age, menopausal status and BMI. Segmentation was subsequently performed on the probe-level test statistics to identify candidate CNV regions that were associated with PD. RESULTS: Sixty-one probes from five chromosomal regions [3q26.1 (2 regions), 8q24.22, 11p15.3, and 17q22] were significantly associated with PD in MBCFS (p-values <0.0001). A CNV at 3q26.1 showed the greatest evidence for association with PD; a region without any known SNPs. Conversely, the CNV at 17q22 was largely due to the association between SNPs and PD in the region. SNPs in the 8q24.22 region have been shown to be associated with risk of many cancers; however, SNPs in this region were not responsible for the observed CNV association. While we were unable to replicate the associations with PD, two of the five CNVs (3q26.1 and 11p15.3) were also observed in the Mayo VTE controls. CONCLUSIONS: CNVs may help to explain some of the variability in PD that is currently unexplained by SNPs. While we were able to replicate the existence of two CNVs across the two GWAS studies, we were unable to replicate the associations with PD. Even so, the proximity of the identified CNV regions to loci known to be associated with breast cancer risk suggests further investigation and potentially shared genetic mechanisms underlying the PD and breast cancer association. PMID- 26152681 TI - Ischemic Heart Disease Worldwide, 1990 to 2013: Estimates From the Global Burden of Disease Study 2013. PMID- 26152680 TI - Clinical Prediction Models for Cardiovascular Disease: Tufts Predictive Analytics and Comparative Effectiveness Clinical Prediction Model Database. AB - BACKGROUND: Clinical prediction models (CPMs) estimate the probability of clinical outcomes and hold the potential to improve decision making and individualize care. For patients with cardiovascular disease, there are numerous CPMs available although the extent of this literature is not well described. METHODS AND RESULTS: We conducted a systematic review for articles containing CPMs for cardiovascular disease published between January 1990 and May 2012. Cardiovascular disease includes coronary heart disease, heart failure, arrhythmias, stroke, venous thromboembolism, and peripheral vascular disease. We created a novel database and characterized CPMs based on the stage of development, population under study, performance, covariates, and predicted outcomes. There are 796 models included in this database. The number of CPMs published each year is increasing steadily over time. Seven hundred seventeen (90%) are de novo CPMs, 21 (3%) are CPM recalibrations, and 58 (7%) are CPM adaptations. This database contains CPMs for 31 index conditions, including 215 CPMs for patients with coronary artery disease, 168 CPMs for population samples, and 79 models for patients with heart failure. There are 77 distinct index/outcome pairings. Of the de novo models in this database, 450 (63%) report a c-statistic and 259 (36%) report some information on calibration. CONCLUSIONS: There is an abundance of CPMs available for a wide assortment of cardiovascular disease conditions, with substantial redundancy in the literature. The comparative performance of these models, the consistency of effects and risk estimates across models and the actual and potential clinical impact of this body of literature is poorly understood. PMID- 26152682 TI - Intracranial Hemorrhage After Ischemic Stroke: Incidence, Time Trends, and Predictors in a Swedish Nationwide Cohort of 196 765 Patients. AB - BACKGROUND: Epidemiological data on the risk of intracranial hemorrhage (ICrH) after ischemic stroke are sparse. The aims of this study were to describe incidence, trends over time, and predictors of ICrH within 1 year after ischemic stroke. METHODS AND RESULTS: All patients registered in the Swedish stroke register Riksstroke for 1998 to 2009 were included (n=196 765), and data were combined with the National Patient Register to identify ICrH occurrence. A matched reference population was obtained. Incidence rates and cumulative incidences were calculated. Multivariable regression analyses were used to identify predictors. Analyses were performed separately for the first 30 days and days 31 to 365 after ischemic stroke. The incidence rate was 1.97% per year at risk for the first year (0.13% in the reference population) and 0.85% excluding the first 30 days. Over time, the cumulative incidence increased the first 30 days but decreased over days 31 to 365. Thrombolysis, previous ICrH, atrial fibrillation, and male sex were associated with increased risk of ICrH during the first 30 days. Previous ICrH, increasing age, and male sex were associated with increased risk during days 31 to 365. Statins and antithrombotic treatment did not independently predict ICrH occurrence. CONCLUSIONS: The incidence of ICrH within 1 year after ischemic stroke was ~2% per year at risk, about 15 times higher compared with the reference population. Over the study period, ICrH risk increased within the first 30 days but decreased thereafter. Previous ICrH, thrombolysis, and male sex affected the risk, whereas an increased use of antithrombotic treatments and statins did not. PMID- 26152684 TI - Realizing the Potential of Clinical Risk Prediction Models: Where Are We Now and What Needs to Change to Better Personalize Delivery of Care? PMID- 26152683 TI - Sex-Stratified Trends in Enrollment, Patient Characteristics, Treatment, and Outcomes Among Non-ST-Segment Elevation Acute Coronary Syndrome Patients: Insights From Clinical Trials Over 17 Years. AB - BACKGROUND: Adequate representation by sex in trials allows generalizability of results. We examined representation of women in clinical trials during a 17-year period in which inclusion criteria were broadened and federal mandates for representativeness were launched. METHODS AND RESULTS: Using mixed models, we studied sex-stratified temporal trends in enrollment, clinical characteristics, treatment, and outcomes among 76 148 non-ST-segment elevation acute coronary syndrome patients using patient-level data merged from 11 phase III trials conducted from 1994 to 2010. Overall, 33.3% of patients were women, which changed minimally over time. Women were consistently 4 to 5 years older than men (median age 68 [interquartile range 61-75] versus 64 [interquartile range 56-72] years) and more frequently had diabetes mellitus, hypertension, and heart failure; men more frequently had prior myocardial infarction and revascularization. GRACE risk scores increased over time for both sexes with the inclusion of older patients with more comorbidities. Use of percutaneous coronary intervention, in-hospital and discharge angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, beta-blockers, and lipid-lowering drugs also increased among both sexes. Kaplan-Meier estimates of 6-month mortality declined from 7.0% [95% confidence interval 6.5%-7.6%] to 4.5% [95% confidence interval 4.0%-5.0%] among women and 6.3% [95% confidence interval 6.0%-6.7%] to 3.1% [95% confidence interval 2.9%-3.4%] among men during the 17-year period. CONCLUSIONS: The relative proportion of women in non-ST-segment elevation acute coronary syndrome trials changed minimally over time. Nevertheless, in parallel with men, use of evidence-based care and outcomes improved significantly over time among women. PMID- 26152685 TI - Optimization of stent implantation using a high pressure inflation protocol. AB - BACKGROUND: High-pressure inflation is the universal standard for stent deployment but a specific protocol for its use is lacking. We developed a standardized "pressure optimization protocol" (POP) using time to inflation pressure stability as an endpoint for determining the required duration of stent inflation. OBJECTIVES: The primary study purpose was to determine the stent inflation time (IT) in a large patient cohort using the standardized inflation protocol, to correlate various patient and lesion characteristics with IT, and ascertain in an in vitro study the time for pressure accommodation within an inflation system. METHODS: Six hundred fifteen stent implants in 435 patients were studied. Multivariate analysis was performed to determine predictors of longer ITs. In an in vitro study, various stents and balloons were inflated in air to determine the pressure accommodation time of the inflation system. RESULTS: The mean stent IT was 104 +/- 41 sec (range 30-380 sec). Stent length was the only predictor of prolonged stent inflation. The "accommodation time" in vitro of the stent inflation system itself was 33 +/- 24 sec. The protocol was safe requiring premature inflation termination in <3% of stent implants. No serious adverse events occurred. CONCLUSIONS: Achieving stable inflation pressure requires on average over 100 sec and may require several minutes in individual cases. Stent length increases IT. These results suggest that the widespread practice of rapid inflation/deflation may not be sufficient to fully expand the stent and that the use of a pressure stability protocol will allow for safe, predictable, and more complete stent deployment. (c) 2015 Wiley Periodicals, Inc. PMID- 26152686 TI - Identification of gene signatures regulated by carvedilol in mouse heart. AB - Chronic treatment with the beta-blocker carvedilol has been shown to reduce established maladaptive left ventricle (LV) hypertrophy and to improve LV function in experimental heart failure. However, the detailed mechanisms by which carvedilol improves LV failure are incompletely understood. We previously showed that carvedilol is a beta-arrestin-biased beta1-adrenergic receptor ligand, which activates cellular pathways in the heart independent of G protein-mediated second messenger signaling. More recently, we have demonstrated by microRNA (miR) microarray analysis that carvedilol upregulates a subset of mature and pre-mature miRs, but not their primary miR transcripts in mouse hearts. Here, we next sought to identify the effects of carvedilol on LV gene expression on a genome-wide basis. Adult mice were treated with carvedilol or vehicle for 1 wk. RNA was isolated from LV tissue and hybridized for microarray analysis. Gene expression profiling analysis revealed a small group of genes differentially expressed after carvedilol treatment. Further analysis categorized these genes into pathways involved in tight junction, malaria, viral myocarditis, glycosaminoglycan biosynthesis, and arrhythmogenic right ventricular cardiomyopathy. Genes encoding proteins in the tight junction, malaria, and viral myocarditis pathways were upregulated in the LV by carvedilol, while genes encoding proteins in the glycosaminoglycan biosynthesis and arrhythmogenic right ventricular cardiomyopathy pathways were downregulated by carvedilol. These gene expression changes may reflect the molecular mechanisms that underlie the functional benefits of carvedilol therapy. PMID- 26152687 TI - Toxicity of CeO2 nanoparticles on a freshwater experimental trophic chain: A study in environmentally relevant conditions through the use of mesocosms. AB - The toxicity of CeO2 NPs on an experimental freshwater ecosystem was studied in mesocosm, with a focus being placed on the higher trophic level, i.e. the carnivorous amphibian species Pleurodeles waltl. The system comprised species at three trophic levels: (i) bacteria, fungi and diatoms, (ii) Chironomus riparius larvae as primary consumers and (iii) Pleurodeles larvae as secondary consumers. NP contamination consisted of repeated additions of CeO2 NPs over 4 weeks, to obtain a final concentration of 1 mg/L. NPs were found to settle and accumulate in the sediment. No effects were observed on litter decomposition or associated fungal biomass. Changes in bacterial communities were observed from the third week of NP contamination. Morphological changes in CeO2 NPs were observed at the end of the experiment. No toxicity was recorded in chironomids, despite substantial NP accumulation (265.8 +/- 14.1 mg Ce/kg). Mortality (35.3 +/- 6.8%) and a mean Ce concentration of 13.5 +/- 3.9 mg/kg were reported for Pleurodeles. Parallel experiments were performed on Pleurodeles to determine toxicity pathways: no toxicity was observed by direct or dietary exposures, although Ce concentrations almost reached 100 mg/kg. In view of these results, various toxicity mechanisms are proposed and discussed. The toxicity observed on Pleurodeles in mesocosm may be indirect, due to microorganism's interaction with CeO2 NPs, or NP dissolution could have occurred in mesocosm due to the structural complexity of the biological environment, resulting in toxicity to Pleurodeles. This study strongly supports the importance of ecotoxicological assessment of NPs under environmentally relevant conditions, using complex biological systems. PMID- 26152688 TI - Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity. AB - Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 MUg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered. PMID- 26152689 TI - Methylation-associated Has-miR-9 deregulation in paclitaxel- resistant epithelial ovarian carcinoma. AB - BACKGROUND: Drug resistance is still one of the key causes of death in epithelial ovarian carcinoma (EOC) patients, however there are very few strategies to reverse chemoresistance. Here we try to clarify whether and how miR-9 takes part in the regulation of paclitaxel sensitivity. METHODS: miR-9 expressions in EOC cells and tissues were detected by Realtime PCR. The target of miR-9 was validated through dual luciferase reporter assay and Western Blot. Methylation study, RNAi technique and cytotoxicity assay were used to determine the intrinsic mechanism of miR-9 in paclitaxel sensitivity regulation. RESULTS: miR-9 is down regulated in paclitaxel resistant EOC. The patients with lower miR-9, Grade 3, Stage III -IV and suboptimal surgery present shorter survival time. miR-9 and suboptimal surgery are independent prognostic factors of EOC. Modulating miR-9 expression could change paclitaxel sensitivity of EOC cells. CCNG1, validated as a direct target of miR-9, mediates paclitaxel resistance. miR-9-1 and 3 gene hypermethylation would decrease miR-9 expression, while demethylation of miR-9 gene could restore miR-9 expression and improve paclitaxel sensitivity in chemoresistance EOC cells. Furthermore, methylation-associated miR-9 deregulation in EOC cells could be induced by paclitaxel exposure. CONCLUSIONS: Methylation associated miR-9 down-regulation is probably one of the key mechanisms for paclitaxel resistance in EOC cells, via targeting CCNG1. Our findings may also provide a new potential therapeutic target to reverse paclitaxel resistance in EOC patients. PMID- 26152690 TI - Effect of N-acetylcysteine and allopurinol combination to protect spinal cord ischemia/reperfusion injury induced by aortic cross-clamping in rat model. AB - PURPOSE: The aim of this experimental study was to determine whether combination of N-acetylcysteine and allopurinol can reduce the ischemia/reperfusion injury of spinal cord in a rat model. METHODS: Twenty-seven Spraque Dawley rats, all male, weighing between 220 to 370 (mean 325) gr were used in the study. 27 rats were divided into three groups: sham group, control group and experimental group. Abdominal aortic occlusion between the renal arteries and iliac bifurcations was carried out for 60 min with proximal and distal clip in control and experimental groups. Hindlimb motor functions were evaluated at 24, and 48 h using the Tarlov Scale. Besides, spinal cord samples were taken for determination of superoxide dismutase, and catalase activities as antioxidant enzymes, and malondialdehyde as an indicator of lipid peroxidation and xanthine oxidase levels as source hydroxyl radical for biochemical studies. Also, histopathological evaluation was made from cord tissue samples. RESULTS: The experimental group subjects had better neurological functions than control group subjects. In experimental group; superoxide dismutase and catalase levels increased, while malondialdehyde and xantine oxidase levels decreased as compared with control group. Histopathological examination showed that experimental group had less cell degeneration, hemorrhage, edema and inflammation loss than control group. CONCLUSIONS: This study offers that combined use of N-acetylcysteine and allopurinol might help protect the spinal cord against ischemia/reperfusion injury. PMID- 26152691 TI - High-dose chloroquine is metabolically cardiotoxic by inducing lysosomes and mitochondria dysfunction in a rat model of pressure overload hypertrophy. AB - Autophagy, macroautophagy and chaperone-mediated autophagy (CMA), are upregulated in pressure overload (PO) hypertrophy. In this study, we targeted this process at its induction using 3 methyladenine and at the lysosomal level using chloroquine and evaluated the effects of these modulations on cardiac function and myocyte ultrastructure. Sprague-Dawley rats weighing 200 g were subjected to ascending aortic banding. After 1 week of PO, animals were randomized to receive 3 methyladenine versus chloroquine, intraperitoneally, for 2 weeks at a dose of 40 and 50 mg/kg/day, respectively. Saline injection was used as control. Chloroquine treatment, in PO, resulted in regression in cardiac hypertrophy but with significant impairments in cardiac relaxation and contractility. Ultrastructurally, chloroquine accentuated mitochondrial fragmentation and cristae destruction with a plethora of autophagosomes containing collapsed mitochondria and lysosomal lamellar bodies. In contrast, 3 methyladenine improved cardiac function and attenuated mitochondrial fragmentation and autophagososme formation. Markers of macroautophagy and CMA were significantly decreased in the chloroquine group; whereas 3 methyladenine treatment significantly attenuated macroautophagy with a compensatory increase in CMA. Furthermore, chloroquine accentuated PO induced oxidative stress through the further decrease in the expression of manganese superoxide dismutase; whereas, 3 MA had a completely opposite effect. Taken together, these data suggest that high-dose chloroquine, in addition to its effect on the autophagy-lysosome pathway, significantly impairs mitochondrial antioxidant buffering capacity and accentuates oxidative stress and mitochondrial dysfunction in PO hypertrophy; highlighting, the cautious administration of this drug in high oxidative stress conditions, such as pathological hypertrophy or heart failure. PMID- 26152692 TI - Unchanged content of oxidative enzymes in fast-twitch muscle fibers and VO2 kinetics after intensified training in trained cyclists. AB - The present study examined if high intensity training (HIT) could increase the expression of oxidative enzymes in fast-twitch muscle fibers causing a faster oxygen uptake (VO2) response during intense (INT), but not moderate (MOD), exercise and reduce the VO2 slow component and muscle metabolic perturbation during INT. Pulmonary VO2 kinetics was determined in eight trained male cyclists (VO2-max: 59 +/- 4 (means +/- SD) mL min(-1) kg(-1)) during MOD (205 +/- 12 W ~65% VO2-max) and INT (286 +/- 17 W ~85% VO2-max) exercise before and after a 7 week HIT period (30-sec sprints and 4-min intervals) with a 50% reduction in volume. Both before and after HIT the content in fast-twitch fibers of CS (P < 0.05) and COX-4 (P < 0.01) was lower, whereas PFK was higher (P < 0.001) than in slow-twitch fibers. Content of CS, COX-4, and PFK in homogenate and fast-twitch fibers was unchanged with HIT. Maximal activity (MUmol g DW(-1) min(-1)) of CS (56 +/- 8 post-HIT vs. 59 +/- 10 pre-HIT), HAD (27 +/- 6 vs. 29 +/- 3) and PFK (340 +/- 69 vs. 318 +/- 105) and the capillary to fiber ratio (2.30 +/- 0.16 vs. 2.38 +/- 0.20) was unaltered following HIT. VO2 kinetics was unchanged with HIT and the speed of the primary response did not differ between MOD and INT. Muscle creatine phosphate was lower (42 +/- 15 vs. 66 +/- 17 mmol kg DW(-1)) and muscle lactate was higher (40 +/- 18 vs. 14 +/- 5 mmol kg DW(-1)) at 6 min of INT (P < 0.05) after compared to before HIT. A period of intensified training with a volume reduction did not increase the content of oxidative enzymes in fast-twitch fibers, and did not change VO2 kinetics. PMID- 26152693 TI - Effect of glaucoma medications on 24-hour intraocular pressure-related patterns using a contact lens sensor. AB - BACKGROUND: The aim of this article was to study the circadian intraocular pressure (IOP)-related effects of ocular hypotensive medications using a contact lens sensor (CLS). DESIGN: This is a university-based prospective, randomized, crossover trial. PARTICIPANTS: A total of 23 patients with primary open-angle glaucoma participated. METHODS: Patients underwent ambulatory recording of IOP related patterns for 24 h in one eye during 3 monthly sessions using a CLS. Patients were untreated in session 1 (S1), were randomized to one of four classes of glaucoma drops for S2 and had a prostaglandin analogue add-on for S3. MAIN OUTCOME MEASURES: Changes in IOP-related patterns were defined using (i) slopes from wake/sitting to sleep/supine; (ii) cosinor rhythmometry modelling; and (iii) area under receiver operating curve (AUC) of sleep period. RESULTS: Mean patient age was 63.8 +/- 11.8 years. Positive linear slopes were seen from wake/sitting to sleep/supine at S1 (17.1 +/- 14.2 mVeq/h) and S2 (5.5 +/- 23.9 mVeq/h) and negative slopes at S3 (-1.9 +/- 29.4 mVeq/h) (S1-S2, P = 0.01; S1-S3, P = 0.02). In the prostaglandin group, slopes changed significantly with introduction of drops (S1-S2, P < 0.024), whereas they did not in a mixed group combining the three other classes (S1-S2, P = 0.060). Overall, cosinor amplitudes were 98.4 +/- 46.5 mVeq (S1), 113.0 +/- 35.6 mVeq (S2) and 109.6 +/- 58.3 mVeq (S3) (S1-S2, P = 0.23; S1-S3, P = 0.66; S2-S3, P = 0.93). AUC were 91.8 +/- 63.0 mVeq (S1), 76.3 +/- 102.7 mVeq (S2) and 19.9 +/- 135.8 mVeq (S3). Differences between sessions were not statistically significant (S1-S2, P = 0.541; S1-S3, P = 0.083; S2-S3, P = 0.092). CONCLUSIONS: Prostaglandin analogues, but not other medications, seem to flatten the IOP-related increase at transition of the wake/sitting to the sleep/supine period, but do not seem to have an effect on acrophase and amplitude. PMID- 26152694 TI - Reelin protects against amyloid beta toxicity in vivo. AB - Alzheimer's disease (AD) is a currently incurable neurodegenerative disorder and is the most common form of dementia in people over the age of 65 years. The predominant genetic risk factor for AD is the epsilon4 allele encoding apolipoprotein E (ApoE4). The secreted glycoprotein Reelin enhances synaptic plasticity by binding to the multifunctional ApoE receptors apolipoprotein E receptor 2 (Apoer2) and very low density lipoprotein receptor (Vldlr). We have previously shown that the presence of ApoE4 renders neurons unresponsive to Reelin by impairing the recycling of the receptors, thereby decreasing its protective effects against amyloid beta (Abeta) oligomer-induced synaptic toxicity in vitro. We showed that when Reelin was knocked out in adult mice, these mice behaved normally without overt learning or memory deficits. However, they were strikingly sensitive to amyloid-induced synaptic suppression and had profound memory and learning disabilities with very low amounts of amyloid deposition. Our findings highlight the physiological importance of Reelin in protecting the brain against Abeta-induced synaptic dysfunction and memory impairment. PMID- 26152696 TI - Function and dysfunction of two-pore channels. AB - Two-pore channels (TPCs) are evolutionarily important members of the voltage gated ion channel superfamily. TPCs localize to acidic Ca(2+) stores within the endolysosomal system. Most evidence indicate that TPCs mediate Ca(2+) signals through the Ca(2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) to control a range of Ca(2+)-dependent events. Recent studies clarify the mechanism of TPC activation and identify roles for TPCs in disease, highlighting the regulation of endolysosomal membrane traffic by local Ca(2+) fluxes. Chemical targeting of TPCs to maintain endolysosomal "well-being" may be beneficial in disorders as diverse as Parkinson's disease, fatty liver disease, and Ebola virus infection. PMID- 26152697 TI - Proteotoxic stress reprograms the chromatin landscape of SUMO modification. AB - The small ubiquitin-like modifier 2 (SUMO-2) is required for survival when cells are exposed to treatments that induce proteotoxic stress by causing the accumulation of misfolded proteins. Exposure of cells to heat shock or other forms of proteotoxic stress induces the conjugation of SUMO-2 to proteins in the nucleus. We investigated the chromatin landscape of SUMO-2 modifications in response to heat stress. Through chromatin immunoprecipitation assays coupled to high-throughput DNA sequencing and mRNA sequencing, we showed that in response to heat shock, SUMO-2 accumulated at nucleosome-depleted, active DNA regulatory elements, which represented binding sites for large protein complexes and were predominantly associated with active genes. However, SUMO did not act as a direct transcriptional repressor or activator of these genes during heat shock. Instead, integration of our results with published proteomics data on heat shock-induced SUMO-2 substrates supports a model in which the conjugation of SUMO-2 to proteins acts as an acute stress response that is required for the stability of protein complexes involved in gene expression and posttranscriptional modification of mRNA. We showed that the conjugation of SUMO-2 to chromatin-associated proteins is an integral component of the proteotoxic stress response, and propose that SUMO-2 fulfills its essential role in cell survival by contributing to the maintenance of protein complex homeostasis. PMID- 26152695 TI - Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation. AB - Nitric oxide (NO) is a signaling intermediate during glutamatergic neurotransmission in the central nervous system (CNS). NO signaling is in part accomplished through cysteine S-nitrosylation, a posttranslational modification by which NO regulates protein function and signaling. In our investigation of the protein targets and functional impact of S-nitrosylation in the CNS under physiological conditions, we identified 269 S-nitrosocysteine residues in 136 proteins in the wild-type mouse brain. The number of sites was significantly reduced in the brains of mice lacking endothelial nitric oxide synthase (eNOS(-/ )) or neuronal nitric oxide synthase (nNOS(-/-)). In particular, nNOS(-/-) animals showed decreased S-nitrosylation of proteins that participate in the glutamate/glutamine cycle, a metabolic process by which synaptic glutamate is recycled or oxidized to provide energy. (15)N-glutamine-based metabolomic profiling and enzymatic activity assays indicated that brain extracts from nNOS( /-) mice converted less glutamate to glutamine and oxidized more glutamate than those from mice of the other genotypes. GLT1 [also known as EAAT2 (excitatory amino acid transporter 2)], a glutamate transporter in astrocytes, was S nitrosylated at Cys(373) and Cys(561) in wild-type and eNOS(-/-) mice, but not in nNOS(-/-) mice. A form of rat GLT1 that could not be S-nitrosylated at the equivalent sites had increased glutamate uptake compared to wild-type GLT1 in cells exposed to an S-nitrosylating agent. Thus, NO modulates glutamatergic neurotransmission through the selective, nNOS-dependent S-nitrosylation of proteins that govern glutamate transport and metabolism. PMID- 26152698 TI - Measuring Cytokinin Levels in the Root Tip by the Zeptomole. PMID- 26152700 TI - Expression and activity of the Calvin-Benson-Bassham cycle transcriptional regulator CbbR from Acidithiobacillus ferrooxidans in Ralstonia eutropha. AB - Autotrophic fixation of carbon dioxide into cellular carbon occurs via several pathways but quantitatively, the Calvin-Benson-Bassham cycle is the most important. CbbR regulates the expression of the cbb genes involved in CO2 fixation via the Calvin-Benson-Bassham cycle in a number of autotrophic bacteria. A gene potentially encoding CbbR (cbbR(AF)) has been predicted in the genome of the chemolithoautotrophic, extreme acidophile Acidithiobacillus ferrooxidans. However, this microorganism is recalcitrant to genetic manipulation impeding the experimental validation of bioinformatic predictions. Two novel functional assays were devised to advance our understanding of cbbR(AF) function using the mutated facultative autotroph Ralstonia eutropha H14 DeltacbbR as a surrogate host to test gene function: (i) cbbR(AF) was expressed in R. eutropha and was able to complement DeltacbbR; and (ii) CbbR(AF) was able to regulate the in vivo activity of four A. ferrooxidans cbb operon promoters in R. eutropha. These results open up the use of R. eutropha as a surrogate host to explore cbbR(AF) activity. PMID- 26152699 TI - Cell-Type-Specific Cytokinin Distribution within the Arabidopsis Primary Root Apex. AB - Cytokinins (CKs) play a crucial role in many physiological and developmental processes at the levels of individual plant components (cells, tissues, and organs) and by coordinating activities across these parts. High-resolution measurements of intracellular CKs in different plant tissues can therefore provide insights into their metabolism and mode of action. Here, we applied fluorescence-activated cell sorting of green fluorescent protein (GFP)-marked cell types, combined with solid-phase microextraction and an ultra-high sensitivity mass spectrometry (MS) method for analysis of CK biosynthesis and homeostasis at cellular resolution. This method was validated by series of control experiments, establishing that protoplast isolation and cell sorting procedures did not greatly alter endogenous CK levels. The MS-based method facilitated the quantification of all the well known CK isoprenoid metabolites in four different transgenic Arabidopsis thaliana lines expressing GFP in specific cell populations within the primary root apex. Our results revealed the presence of a CK gradient within the Arabidopsis root tip, with a concentration maximum in the lateral root cap, columella, columella initials, and quiescent center cells. This distribution, when compared with previously published auxin gradients, implies that the well known antagonistic interactions between the two hormone groups are cell type specific. PMID- 26152701 TI - Nitrogenase expression in estuarine bacterioplankton influenced by organic carbon and availability of oxygen. AB - The genetic capacity to fix gaseous nitrogen (N) is distributed among diverse diazotrophs belonging to the Bacteria and Archaea. However, only a subset of the putative diazotrophs present actively fix N at any given time in the environment. We experimentally tested whether the availability of carbon and inhibition by oxygen constrain N fixation by diazotrophs in coastal seawater. The goal was to test whether by alleviating these constraints an increased overlap between nitrogenase (nifH)-gene-carrying and -expressing organisms could be achieved. We incubated water from a eutrophic but N-limited fjord in Denmark under high carbon/low-oxygen conditions and determined bacterial growth and production, diazotrophic community composition (Illumina nifH amplicon sequencing), and nifH gene abundance and expression [quantitative PCR (qPCR) and quantitative reverse transcriptase PCR (qRT-PCR)]. Bacterial abundances and production increased under high-carbon/low-oxygen conditions as did the similarity between present and active diazotrophic communities. This was caused by the loss of specific abundant yet non-active gammaproteobacterial phylotypes and increased expression by others. The prominent active gamma- and epsilonproteobacterial diazotrophs did not, however, respond to these conditions in a uniform way, highlighting the difficulty to assess how a change in environmental conditions may affect a diverse indigenous diazotrophic community. PMID- 26152702 TI - Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity. AB - INTRODUCTION: High-dose methotrexate (doses >=1 g/m(2)) is a key component of several chemotherapy regimens used to treat patients with leukemia or lymphoma. Despite appropriate precautions with hydration, urine alkalinization, and leucovorin, nephrotoxicity remains a risk which can lead to significant morbidity and mortality. Current reports of risk factors for nephrotoxicity focus on patients with nephrotoxicity with a lack of comparison to those without toxicity. This study aimed to describe the incidence of high-dose methotrexate-induced nephrotoxicity at our institution and determined risk factors for high-dose methotrexate-induced nephrotoxicity by examining characteristics of patients with and without nephrotoxicity. METHODS: This was a retrospective, single-center, chart review. Adult patients with a diagnosis of leukemia or lymphoma who received high-dose methotrexate were included. Serum creatinine values were used to evaluate nephrotoxicity according to Common Terminology Criteria for Adverse Events criteria v4.03. Data related to the following proposed risk factors were collected: age, sex, body mass index, methotrexate dose, number of high-dose methotrexate exposures, leucovorin administration route, baseline renal function, albumin, hydration status, Clostridium difficile infection, urine pH, and concomitant interacting and nephrotoxic medications. The primary endpoint was evaluated with exact binomial methods and risk factors were identified using multivariable random-effects logistic regression. RESULTS: Final analyses included 140 patients with 432 high-dose methotrexate exposures. There were no differences in baseline demographical characteristics. Fifty-four patients (38.6%) experienced nephrotoxicity of any grade: 27.9% with grade 1, 5.7% with grade 2, 3.6% grade 3, 0% with grade 4, and 1.4% with grade 5 toxicity. More patients in the toxicity group received doses of methotrexate >=3 g/m(2) (58.3% versus 57.2%, p < 0.001), had an albumin level <3 g/dL (31.9% versus 15.9%, p = 0.04), and received an interacting medication during high-dose methotrexate clearance (44.4% versus 24.7%, p = 0.003). Male gender (OR 2.3, 95% CI: 1.27 4.18, p = 0.006), albumin (OR 0.44, 95% CI: 0.26-0.75, p = 0.002), number of drug interactions (OR 1.60, 95% CI: 1.15-2.21, p = 0.005), and use of furosemide (OR 2.56, 95% CI 1.46-4.48, p = 0.001) were all independent risk factors for the development of nephrotoxicity. CONCLUSIONS: Nephrotoxicity is a possible complication of therapy with high-dose methotrexate with most instances comprising grade 1-2 toxicity. Male gender, low albumin, and administration of interacting drugs or furosemide during high-dose methotrexate clearance may predispose patients to nephrotoxicity. PMID- 26152703 TI - Stability of lenalidomide suspension after preparation by a simple suspension method for enteral tube administration. AB - PURPOSE: A simple suspension method has been developed for tube administration, in which tablets (and capsules) are disintegrated in hot water (55C) without grinding (or opening) them. In the present study, we evaluated the feasibility of this simple suspension method for the preparation of lenalidomide (Celgene, Summit, New Jersey and USA) suspension by testing the stability of this drug at 55C and its adsorbability on the tube. METHODS: We examined, by high-performance liquid chromatography, the time-dependent changes in the concentration of lenalidomide in suspensions of the drug prepared by the simple suspension method. The high-performance liquid chromatography analyses of lenalidomide were performed on Prominence LC-20AB/SPD-20 A (Shimadzu, Kyoto, Japan) with a ZORBAX SB-C18 RR analytical column (Agilent Technologies, Santa Clara, California, USA; particle size: 2.1 * 100 mm, 3.5 um) at a flow rate of 0.4 mL/min. A solvent system consisting of 10 mM ammonium acetate (pH 7.0)/acetonitrile was used as the eluent and the eluate was detected by UV at 254 nm. RESULTS: Lenalidomide was confirmed to remain stable in hot water at 55C for 24 h in the prepared suspension by the simple suspension method, and more than 99% of the drug could be recovered from the suspension. In addition, 94.5-98.0% of the drug amount could pass through a percutaneous endoscopic gastrostomy tube. Lenalidomide was scarcely adsorbed on to the percutaneous endoscopic gastrostomy tube made of polyurethane or polyvinyl chloride. CONCLUSION: Lenalidomide was found to be stable even in hot water and was not adsorbed on to the percutaneous endoscopic gastrostomy tube. PMID- 26152704 TI - Corrigendum. AB - Greitemeyer, T., & Mugge, D. O. (2014). Video games do affect social outcomes: A meta-analytic review of the effects of violent and prosocial video game play. Personality and Social Psychology Bulletin, 40(5), 578-589. (Original DOI: 10.1177/0146167213520459). PMID- 26152705 TI - Nonequilibrium Energy Transfer at Nanoscale: A Unified Theory from Weak to Strong Coupling. AB - Unraveling the microscopic mechanism of quantum energy transfer across two-level systems provides crucial insights to the optimal design and potential applications of low-dimensional nanodevices. Here, we study the non-equilibrium spin-boson model as a minimal prototype and develop a fluctuation-decoupled quantum master equation approach that is valid ranging from the weak to the strong system-bath coupling regime. The exact expression of energy flux is analytically established, which dissects the energy transfer as multiple boson processes with even and odd parity. Our analysis provides a unified interpretation of several observations, including coherence-enhanced heat flux and negative differential thermal conductance. The results will have broad implications for the fine control of energy transfer in nano-structural devices. PMID- 26152707 TI - Yes, We Can! (Should We?). PMID- 26152706 TI - High-Sensitivity Cardiac Troponin T and Risk of Hypertension. AB - BACKGROUND: The diagnosis of hypertension is often preceded by cardiac structural abnormalities. Thus, we assessed whether high-sensitivity cardiac troponin T (hs cTnT), a marker of subclinical myocardial damage, can identify individuals at risk for hypertension or left ventricular hypertrophy. METHODS AND RESULTS: We studied 6516 Atherosclerosis Risk in Communities (ARIC) Study participants who were free of prevalent hypertension and cardiovascular disease at baseline (1990 1992). We examined the association of baseline hs-cTnT categories with incident diagnosed hypertension (defined by self-report of a diagnosis or medication use during a maximum of 19.9 years of follow-up) and with incident visit-based hypertension (defined by self-report, medication use, or measured blood pressure >140/90 mm Hg over 6 years). Relative to hs-cTnT <5 ng/L, adjusted hazard ratios for incident diagnosed hypertension were 1.16 (95% confidence interval, 1.08 1.25) for individuals with hs-cTnT of 5 to 8 ng/L, 1.29 (95% confidence interval, 1.14-1.47) for hs-cTnT of 9 to 13 ng/L, and 1.31 (95% confidence interval, 1.07 1.61) for hs-cTnT >=14 ng/L (P for trend <0.001). Associations were stronger for incident visit-based hypertension. These associations were driven by higher relative hazard in normotensive people (compared with those with prehypertension; P for interaction=0.001). Baseline hs-cTnT was also strongly associated with incident left ventricular hypertrophy by electrocardiography over 6 years (eg, adjusted hazard ratio, 5.19 [95% confidence interval, 1.49-18.08] for hs-cTnT >=14 versus <5 ng/L). Findings were not appreciably changed after accounting for competing deaths or adjusting for baseline blood pressure levels or N-terminal probrain natriuretic peptide. CONCLUSIONS: In an ambulatory population with no history of cardiovascular disease, hs-cTnT was associated with incident hypertension and risk of left ventricular hypertrophy. Further research is needed to determine whether hs-cTnT can identify people who may benefit from ambulatory blood pressure monitoring or hypertension prevention lifestyle strategies. PMID- 26152708 TI - Percutaneous Coronary Intervention at Centers With and Without On-Site Surgical Backup: An Updated Meta-Analysis of 23 Studies. AB - BACKGROUND: Emergency coronary artery bypass grafting for unsuccessful percutaneous coronary intervention (PCI) is now rare. We aimed to evaluate the current safety and outcomes of primary PCI and nonprimary PCI at centers with and without on-site surgical backup. METHODS AND RESULTS: We performed an updated systematic review and meta-analysis by using mixed-effects models. We included 23 high-quality studies that compared clinical outcomes and complication rates of 1 101 123 patients after PCI at centers with or without on-site surgery. For primary PCI for ST-segment-elevation myocardial infarction (133 574 patients), all-cause mortality (without on-site surgery versus with on-site surgery: observed rates, 4.8% versus 7.2%; pooled odds ratio [OR], 0.99; 95% confidence interval, 0.91-1.07; P=0.729; I(2)=3.4%) or emergency coronary artery bypass grafting rates (observed rates, 1.5% versus 2.4%; pooled OR, 0.76; 95% confidence interval, 0.56-1.01; P=0.062; I(2)=42.5%) did not differ by presence of on-site surgery. For nonprimary PCI (967 549 patients), all-cause mortality (observed rates, 1.6% versus 2.1%; pooled OR, 1.15; 95% confidence interval, 0.94-1.41; P=0.172; I(2)=67.5%) and emergency coronary artery bypass grafting rates (observed rates, 0.5% versus 0.8%; pooled OR, 1.14; 95% confidence interval, 0.62 2.13; P=0.669; I(2)=81.7%) were not significantly different. PCI complication rates (cardiogenic shock, stroke, aortic dissection, tamponade, recurrent infarction) also did not differ by on-site surgical capability. Cumulative meta analysis of nonprimary PCI showed a temporal decrease of the effect size (OR) for all-cause mortality after 2007. CONCLUSIONS: Clinical outcomes and complication rates of PCI at centers without on-site surgery did not differ from those with on site surgery, for both primary and nonprimary PCI. Temporal trends indicated improving clinical outcomes in nonprimary PCI at centers without on-site surgery. PMID- 26152709 TI - Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death: Outcomes at 4 Years From the Reduction of Atherothrombosis for Continued Health (REACH) Registry. AB - BACKGROUND: Despite the known association of diabetes mellitus with cardiovascular events, there are few contemporary data on the long-term outcomes from international cohorts of patients with diabetes mellitus. We sought to describe cardiovascular outcomes at 4 years and to identify predictors of these events in patients with diabetes mellitus. METHODS AND RESULTS: The Reduction of Atherothrombosis for Continued Health (REACH) registry is an international registry of patients at high risk of atherothrombosis or established atherothrombosis. Four-year event rates in patients with diabetes mellitus were determined with the corrected group prognosis method. Of the 45 227 patients in the REACH registry who had follow-up at 4 years, 43.6% (n=19 699) had diabetes mellitus at baseline. The overall risk and hazard ratio (HR) of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were greater in patients with diabetes compared with patients without diabetes (16.5% versus 13.1%; adjusted HR, 1.27; 95% confidence interval [CI] 1.19-1.35). There was also an increase in both cardiovascular death (8.9% versus 6.0%; adjusted HR, 1.38; 95% CI, 1.26-1.52) and overall death (14.3% versus 9.9%; adjusted HR, 1.40; 95% CI, 1.30-1.51). Diabetes mellitus was associated with a 33% greater risk of hospitalization for heart failure (9.4% versus 5.9%; adjusted odds ratio, 1.33; 95% CI, 1.18-1.50). In patients with diabetes mellitus, heart failure at baseline was independently associated with cardiovascular death (adjusted HR, 2.45; 95% CI, 2.17-2.77; P<0.001) and hospitalization for heart failure (adjusted odds ratio, 4.72; 95% CI, 4.22-5.29; P<0.001). CONCLUSIONS: Diabetes mellitus substantially increases the risk of death, ischemic events, and heart failure. Patients with both diabetes mellitus and heart failure are at particularly elevated risk of cardiovascular death, highlighting the need for additional therapies in this high-risk population. PMID- 26152710 TI - Role of protein kinase C in cytokine secretion by lung epithelial cells during infection with Paracoccidioides brasiliensis. AB - In this study, we investigated the role of protein kinases C (PKCs) in interleukin (IL)-6 and IL-8 secretion by human lung epithelial A549 cells during infection with the fungal pathogen Paracoccidioides brasiliensis. Rottlerin and the broad spectrum PKC inhibitor Go 6983 reduced cytokine levels in A549 cell-P. brasiliensis cultures. Next, by western blot, we verified that infection with this fungus led to phosphorylation of PKC delta (Thr(505)). By using a peptide inhibitor for PKC delta or PKC delta short interfering RNA technique, IL-6 and IL 8 levels in A549-P. brasiliensis cultures were also reduced. Together, these results indicate that P. brasiliensis promotes IL-6 and IL-8 secretion by A549 cells in a PKC delta-dependent manner. PMID- 26152712 TI - TRANSPARENT TESTA GLABRA1 Regulates the Accumulation of Seed Storage Reserves in Arabidopsis. AB - Seed storage reserves mainly consist of starch, triacylglycerols, and storage proteins. They not only provide energy for seed germination and seedling establishment, but also supply essential dietary nutrients for human beings and animals. So far, the regulatory networks that govern the accumulation of seed storage reserves in plants are still largely unknown. Here, we show that TRANSPARENT TESTA GLABRA1 (TTG1), which encodes a WD40 repeat transcription factor involved in many aspects of plant development, plays an important role in mediating the accumulation of seed storage reserves in Arabidopsis (Arabidopsis thaliana). The dry weight of ttg1-1 embryos significantly increases compared with that of wild-type embryos, which is accompanied by an increase in the contents of starch, total protein, and fatty acids in ttg1-1 seeds. FUSCA3 (FUS3), a master regulator of seed maturation, binds directly to the TTG1 genomic region and suppresses TTG1 expression in developing seeds. TTG1 negatively regulates the accumulation of seed storage proteins partially through transcriptional repression of 2S3, a gene encoding a 2S albumin precursor. TTG1 also indirectly suppresses the expression of genes involved in either seed development or synthesis/modification of fatty acids in developing seeds. In addition, we demonstrate that the maternal allele of the TTG1 gene suppresses the accumulation of storage proteins and fatty acids in seeds. Our results suggest that TTG1 is a direct target of FUS3 in the framework of the regulatory hierarchy controlling seed filling and regulates the accumulation of seed storage proteins and fatty acids during the seed maturation process. PMID- 26152713 TI - Amyloid-beta peptide-induced cytotoxicity and mitochondrial dysfunction in yeast. AB - Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by deposits of amyloid-beta (Abeta) peptides. However, the underlying molecular mechanisms of neuron cell dysfunction and cell death in AD still remain poorly understood. Yeast Saccharomyces cerevisiae shares many conserved biological processes with all eukaryotic cells, including human neurons. Thanks to relatively simple and quick genetic and environmental manipulations, the large knowledge base and data collections, this organism has become a valuable tool to unravel fundamental intracellular mechanisms underlying neurodegeneration. In this study, we have used yeast as a model system to study the effects of intracellular Abeta peptides and we found that cells constitutively producing native Abeta directed to the secretory pathway exhibited a lower growth rate, lower biomass yield, lower respiratory rate, increased oxidative stress, hallmarks of mitochondrial dysfunction and ubiquitin-proteasome system dysfunction. These findings are relevant for better understanding the role of Abeta in cell stress and cell damage. PMID- 26152711 TI - A Member of the Arabidopsis Mitochondrial Transcription Termination Factor Family Is Required for Maturation of Chloroplast Transfer RNAIle(GAU). AB - Plastid gene expression is crucial for organelle function, but the factors that control it are still largely unclear. Members of the so-called mitochondrial transcription termination factor (mTERF) family are found in metazoans and plants and regulate organellar gene expression at different levels. Arabidopsis (Arabidopsis thaliana) mTERF6 is localized in chloroplasts and mitochondria, and its knockout perturbs plastid development and results in seedling lethality. In the leaky mterf6-1 mutant, a defect in photosynthesis is associated with reduced levels of photosystem subunits, although corresponding messenger RNA levels are unaffected, whereas translational capacity and maturation of chloroplast ribosomal RNAs (rRNAs) are perturbed in mterf6-1 mutants. Bacterial one-hybrid screening, electrophoretic mobility shift assays, and coimmunoprecipitation experiments reveal a specific interaction between mTERF6 and an RNA sequence in the chloroplast isoleucine transfer RNA gene (trnI.2) located in the rRNA operon. In vitro, recombinant mTERF6 bound to its plastid DNA target site can terminate transcription. At present, it is unclear whether disturbed rRNA maturation is a primary or secondary defect. However, it is clear that mTERF6 is required for the maturation of trnI.2. This points to an additional function of mTERFs. PMID- 26152714 TI - Integration of RNA-seq and proteomics data with genomics for improved genome annotation in Apicomplexan parasites. AB - While high quality genomic sequence data is available for many pathogenic organisms, the corresponding gene annotations are often plagued with inaccuracies that can hinder research that utilizes such genomic data. Experimental validation of gene models is clearly crucial in improving such gene annotations; the field of proteogenomics is an emerging area of research wherein proteomic data is applied to testing and improving genetic models. Krishna et al. [Proteomics 2015, 15, 2618-2628] investigated whether incorporation of RNA-seq data into proteogenomics analyses can contribute significantly to validation studies of genome annotation, in two important parasitic organisms Toxoplasma gondii and Neospora caninum. They applied a systematic approach to combine new and previously published proteomics data from T. gondii and N. caninum with transcriptomics data, leading to substantially improved gene models for these organisms. This study illustrates the importance of incorporating experimental data from both proteomics and RNA-seq studies into routine genome annotation protocols. PMID- 26152715 TI - Metformin Inhibits the Production of Reactive Oxygen Species from NADH:Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1beta (IL-1beta) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages. AB - Metformin, a frontline treatment for type II diabetes mellitus, decreases production of the pro-form of the inflammatory cytokine IL-1beta in response to LPS in macrophages. We found that it specifically inhibited pro-IL-1beta production, having no effect on TNF-alpha. Furthermore, metformin boosted induction of the anti-inflammatory cytokine IL-10 in response to LPS. We ruled out a role for AMP-activated protein kinase (AMPK) in the effect of metformin because activation of AMPK with A769662 did not mimic metformin here. Furthermore, metformin was still inhibitory in AMKPalpha1- or AMPKbeta1-deficient cells. The activity of NADH:ubiquinone oxidoreductase (complex I) was inhibited by metformin. Another complex I inhibitor, rotenone, mimicked the effect of metformin on pro-IL-1beta and IL-10. LPS induced reactive oxygen species production, an effect inhibited by metformin or rotenone pretreatment. MitoQ, a mitochondrially targeted antioxidant, decreased LPS-induced IL-1beta without affecting TNF-alpha. These results, therefore, implicate complex I in LPS action in macrophages. PMID- 26152716 TI - Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel. AB - The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr). A reduction in the hERG current causes long QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. We reported previously that hERG channels in the plasma membrane undergo vigorous internalization under low K(+) conditions. In the present study, we addressed whether hERG internalization occurs under normal K(+) conditions and whether/how internalized channels are recycled back to the plasma membrane. Using patch clamp, Western blot, and confocal imaging analyses, we demonstrated that internalized hERG channels can effectively recycle back to the plasma membrane. Low K(+)-enhanced hERG internalization is accompanied by an increased rate of hERG recovery in the plasma membrane upon reculture following proteinase K-mediated clearance of cell surface proteins. The increased recovery rate is not due to enhanced protein synthesis, as hERG mRNA expression was not altered by low K(+) exposure, and the increased recovery was observed in the presence of the protein biosynthesis inhibitor cycloheximide. GTPase Rab11, but not Rab4, is involved in the recycling of hERG channels. Interfering with Rab11 function not only delayed hERG recovery in cells after exposure to low K(+) medium but also decreased hERG expression and function in cells under normal culture conditions. We concluded that the recycling pathway plays an important role in the homeostasis of plasma membrane bound hERG channels. PMID- 26152717 TI - Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Endolysosomal Two-pore Channels Modulate Membrane Excitability and Stimulus-Secretion Coupling in Mouse Pancreatic beta Cells. AB - Pancreatic beta cells are electrically excitable and respond to elevated glucose concentrations with bursts of Ca(2+) action potentials due to the activation of voltage-dependent Ca(2+) channels (VDCCs), which leads to the exocytosis of insulin granules. We have examined the possible role of nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca(2+) release from intracellular stores during stimulus-secretion coupling in primary mouse pancreatic beta cells. NAADP regulated Ca(2+) release channels, likely two-pore channels (TPCs), have recently been shown to be a major mechanism for mobilizing Ca(2+) from the endolysosomal system, resulting in localized Ca(2+) signals. We show here that NAADP-mediated Ca(2+) release from endolysosomal Ca(2+) stores activates inward membrane currents and depolarizes the beta cell to the threshold for VDCC activation and thereby contributes to glucose-evoked depolarization of the membrane potential during stimulus-response coupling. Selective pharmacological inhibition of NAADP evoked Ca(2+) release or genetic ablation of endolysosomal TPC1 or TPC2 channels attenuates glucose- and sulfonylurea-induced membrane currents, depolarization, cytoplasmic Ca(2+) signals, and insulin secretion. Our findings implicate NAADP evoked Ca(2+) release from acidic Ca(2+) storage organelles in stimulus-secretion coupling in beta cells. PMID- 26152718 TI - Interleukin-2 Receptor beta Thr-450 Phosphorylation Is a Positive Regulator for Receptor Complex Stability and Activation of Signaling Molecules. AB - T, B, and natural killer cells are required for normal immune response and are regulated by cytokines such as IL-2. These cell signals are propagated following receptor-ligand engagement, controlling recruitment and activation of effector proteins. The IL-2 receptor beta subunit (IL-2Rbeta) serves in this capacity and is known to be phosphorylated. Tyrosine phosphorylation of the beta chain has been studied extensively. However, the identification and putative regulatory roles for serine and threonine phosphorylation sites have yet to be fully characterized. Using LC-MS/MS and phosphospecific antibodies, a novel IL-2/IL-15 inducible IL-2Rbeta phosphorylation site (Thr-450) was identified. IL-2 phosphokinetic analysis revealed that phosphorylation of IL-2Rbeta Thr-450 is rapid (2.5 min), transient (peaks at 15 min), and protracted compared with receptor tyrosine phosphorylation and occurs in multiple cell types, including primary human lymphocytes. Pharmacological and siRNA-mediated inhibition of various serine/threonine kinases revealed ERK1/2 as a positive regulator, whereas purified protein phosphatase 1 (PP1), dephosphorylated Thr-450 in vitro. Reconstitution assays demonstrated that Thr-450 is important for regulating IL-2R complex formation, recruitment of JAK3, and activation of AKT and ERK1/2 and a transcriptionally active STAT5. These results provide the first evidence of the identification and functional characterization for threonine phosphorylation of an interleukin receptor. PMID- 26152720 TI - Introduction: Metals in Biology: alpha-Ketoglutarate/Iron-Dependent Dioxygenases. AB - Four minireviews deal with aspects of the alpha-ketoglutarate/iron-dependent dioxygenases in this eighth Thematic Series on Metals in Biology. The minireviews cover a general introduction and synopsis of the current understanding of mechanisms of catalysis, the roles of these dioxygenases in post-translational protein modification and de-modification, the roles of the ten-eleven translocation (Tet) dioxygenases in the modification of methylated bases (5mC, T) in DNA relevant to epigenetic mechanisms, and the roles of the AlkB-related dioxygenases in the repair of damaged DNA and RNA. The use of alpha-ketoglutarate (alternatively termed 2-oxoglutarate) as a co-substrate in so many oxidation reactions throughout much of nature is notable and has surprisingly emerged from biochemical and genomic analysis. About 60 of these enzymes are now recognized in humans, and a number have been identified as having critical functions. PMID- 26152719 TI - The Mechanisms of Generation, Recognition, and Erasure of DNA 5-Methylcytosine and Thymine Oxidations. AB - One of the most fundamental questions in the control of gene expression in mammals is how the patterns of epigenetic modifications of DNA are generated, recognized, and erased. This includes covalent cytosine methylation of DNA and its associated oxidation states. An array of AdoMet-dependent methyltransferases, Fe(II)- and alpha-ketoglutarate-dependent dioxygenases, base excision glycosylases, and sequence-specific transcription factors is responsible for changing, maintaining, and interpreting the modification status of specific regions of chromatin. This review focuses on recent developments in characterizing the functional and structural links between the modification status of two DNA bases 5-methylcytosine and thymine (5-methyluracil). PMID- 26152721 TI - Catalytic Mechanisms of Fe(II)- and 2-Oxoglutarate-dependent Oxygenases. AB - Mononuclear non-heme Fe(II)- and 2-oxoglutarate (2OG)-dependent oxygenases comprise a large family of enzymes that utilize an Fe(IV)-oxo intermediate to initiate diverse oxidative transformations with important biological roles. Here, four of the major types of Fe(II)/2OG-dependent reactions are detailed: hydroxylation, halogenation, ring formation, and desaturation. In addition, an atypical epimerization reaction is described. Studies identifying several key intermediates in catalysis are concisely summarized, and the proposed mechanisms are explained. In addition, a variety of other transformations catalyzed by selected family members are briefly described to further highlight the chemical versatility of these enzymes. PMID- 26152722 TI - Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice. AB - We sought to examine interactions of the prion protein (PrP(C)) with monoaminergic systems due to: the role of PrP(C) in both Prion and Alzheimer diseases, which include clinical depression among their symptoms, the implication of monoamines in depression, and the hypothesis that PrP(C) serves as a scaffold for signaling systems. To that effect we compared both behavior and monoaminergic markers in wild type (WT) and PrP(C)-null (PrP(-/-)) mice. PrP(-/-) mice performed poorly when compared with WT in forced swimming, tail suspension, and novelty suppressed feeding tests, typical of depressive-like behavior, but not in the control open field nor rotarod motor tests; cyclic AMP responses to stimulation of D1 receptors by dopamine was selectively impaired in PrP(-/-) mice, and responses to serotonin, but not to norepinephrine, also differed between genotypes. Contents of dopamine, tyrosine hydroxylase, and the 5-HT5A serotonin receptor were increased in the cerebral cortex of PrP(-/-), as compared with WT mice. Microscopic colocalization, as well as binding in overlay assays were found of PrP(C) with both the 5HT5A and D1, but not D4 receptors. The data are consistent with the scaffolding of monoaminergic signaling modules by PrP(C), and may help understand the pathogenesis of clinical depression and neurodegenerative disorders. PMID- 26152723 TI - Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes. AB - Arterial smooth muscle cells (ASMCs) undergo phenotypic changes during development and pathological processes in vivo and during cell culture in vitro. Our previous studies demonstrated that retrovirally mediated expression of the versican V3 splice variant (V3) by ASMCs retards cell proliferation and migration in vitro and reduces neointimal thickening and macrophage and lipid accumulation in animal models of vascular injury and atherosclerosis. However, the molecular pathways induced by V3 expression that are responsible for these changes are not yet clear. In this study, we employed a microarray approach to examine how expression of V3 induced changes in gene expression and the molecular pathways in rat ASMCs. We found that forced expression of V3 by ASMCs affected expression of 521 genes by more than 1.5-fold. Gene ontology analysis showed that components of the extracellular matrix were the most significantly affected by V3 expression. In addition, genes regulating the formation of the cytoskeleton, which also serve as markers of contractile smooth muscle cells (SMCs), were significantly up regulated. In contrast, components of the complement system, chemokines, chemokine receptors, and transcription factors crucial for regulating inflammatory processes were among the genes most down-regulated. Consistently, we found that the level of myocardin, a key transcription factor promoting contractile SMC phenotype, was greatly increased, and the proinflammatory transcription factors NFkappaB1 and CCAAT/enhancer-binding protein beta were significantly attenuated in V3-expressing SMCs. Overall, these findings demonstrate that V3 expression reprograms ASMCs promoting differentiated and anti inflammatory phenotypes. PMID- 26152724 TI - miR-184 Regulates Pancreatic beta-Cell Function According to Glucose Metabolism. AB - In response to fasting or hyperglycemia, the pancreatic beta-cell alters its output of secreted insulin; however, the pathways governing this adaptive response are not entirely established. Although the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the beta cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the beta-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon the administration of a sucrose-rich diet in Drosophila, demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Argonaute2 in the presence of miR-184 rescued suppression of miR-375-targeted genes, suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved. PMID- 26152725 TI - Human Epidermal Growth Factor Receptor 2 (HER2) Impedes MLK3 Kinase Activity to Support Breast Cancer Cell Survival. AB - Human epidermal growth factor receptor 2 (HER2) is amplified in ~ 15-20% of human breast cancer and is important for tumor etiology and therapeutic options of breast cancer. Up-regulation of HER2 oncogene initiates cascades of events cumulating to the stimulation of transforming PI3K/AKT signaling, which also plays a dominant role in supporting cell survival and efficacy of HER2-directed therapies. Although investigating the underlying mechanisms by which HER2 promotes cell survival, we noticed a profound reduction in the kinase activity of a pro-apoptotic mixed lineage kinase 3 (MLK3) in HER2-positive (HER2+) but not in HER2-negative (HER2-) breast cancer tissues, whereas both HER2+ and HER2- tumors expressed a comparable level of MLK3 protein. Furthermore, the kinase activity of MLK3 was inversely correlated with HER2+ tumor grades. Moreover, HER2-directed drugs such as trastuzumab and lapatinib as well as depletion of HER2 or HER3 stimulated MLK3 kinase activity in HER2+ breast cancer cell lines. In addition, the noted inhibitory effect of HER2 on MLK3 kinase activity was mediated via its phosphorylation on Ser(674) by AKT and that pharmacological inhibitors of PI3K/AKT prevented trastuzumab- and lapatinib-induced stimulation of MLK3 activity. Consistent with the pro-apoptotic function of MLK3, stable knockdown of MLK3 in the HER2+ cell line blunted the pro-apoptotic effects of trastuzumab and lapatinib. These findings suggest that HER2 activation inhibits the pro-apoptotic function of MLK3, which plays a mechanistic role in mediating anti-tumor activities of HER2-directed therapies. In brief, MLK3 represents a newly recognized integral component of HER2 biology in HER2+ breast tumors. PMID- 26152726 TI - Functional Characterization of a WWP1/Tiul1 Tumor-derived Mutant Reveals a Paradigm of Its Constitutive Activation in Human Cancer. AB - Although E3 ubiquitin ligases are deemed to play key roles in normal cell function and homeostasis, whether their alterations contribute to cancer pathogenesis remains unclear. In this study, we sought to investigate potential mechanisms that govern WWP1/Tiul1 (WWP1) ubiquitin ligase activity, focusing on its ability to trigger degradation of TGFbeta type I receptor (TbetaRI) in conjunction with Smad7. Our data reveal that the WWP1 protein is very stable at steady states because its autopolyubiquitination activity is silenced due to an intra-interaction between the C2 and/or WW and Hect domains that favors WWP1 monoubiquitination at the expense of its polyubiquitination or polyubiquitination of TbetaRI. Upon binding of WWP1 to Smad7, this functional interplay is disabled, switching its monoubiquitination activity toward a polyubiquitination activity, thereby driving its own degradation and that of TbetaRI as well. Intriguingly, a WWP1 point mutation found in human prostate cancer disrupts this regulatory mechanism by relieving the inhibitory effects of C2 and WW on Hect and thereby causing WWP1 hyperactivation. That cancer-driven alteration of WWP1 culminates in excessive TbetaRI degradation and attenuated TGFbeta cytostatic signaling, a consequence that could conceivably confer tumorigenic properties to WWP1. PMID- 26152728 TI - A Two-step Protein Quality Control Pathway for a Misfolded DJ-1 Variant in Fission Yeast. AB - A mutation, L166P, in the cytosolic protein, PARK7/DJ-1, causes protein misfolding and is linked to Parkinson disease. Here, we identify the fission yeast protein Sdj1 as the orthologue of DJ-1 and calculate by in silico saturation mutagenesis the effects of point mutants on its structural stability. We also map the degradation pathways for Sdj1-L169P, the fission yeast orthologue of the disease-causing DJ-1 L166P protein. Sdj1-L169P forms inclusions, which are enriched for the Hsp104 disaggregase. Hsp104 and Hsp70-type chaperones are required for efficient degradation of Sdj1-L169P. This also depends on the ribosome-associated E3 ligase Ltn1 and its co-factor Rqc1. Although Hsp104 is absolutely required for proteasomal degradation of Sdj1-L169P aggregates, the degradation of already aggregated Sdj1-L169P occurs independently of Ltn1 and Rqc1. Thus, our data point to soluble Sdj1-L169P being targeted early by Ltn1 and Rqc1. The fraction of Sdj1-L169P that escapes this first inspection then forms aggregates that are subsequently cleared via an Hsp104- and proteasome-dependent pathway. PMID- 26152727 TI - The AlkB Family of Fe(II)/alpha-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond. AB - The AlkB family of Fe(II)- and alpha-ketoglutarate-dependent dioxygenases is a class of ubiquitous direct reversal DNA repair enzymes that remove alkyl adducts from nucleobases by oxidative dealkylation. The prototypical and homonymous family member is an Escherichia coli "adaptive response" protein that protects the bacterial genome against alkylation damage. AlkB has a wide variety of substrates, including monoalkyl and exocyclic bridged adducts. Nine mammalian AlkB homologs exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes. This minireview presents an overview of the AlkB proteins including recent data on homologs, structural features, substrate specificities, and experimental strategies for studying DNA repair by AlkB family proteins. PMID- 26152729 TI - Intracellular Ascorbate Prevents Endothelial Barrier Permeabilization by Thrombin. AB - Intracellular ascorbate (vitamin C) has previously been shown to tighten the endothelial barrier and maintain barrier integrity during acute inflammation in vitro. However, the downstream effectors of ascorbate in the regulation of endothelial permeability remain unclear. In this study, we evaluated ascorbate as a mediator of thrombin-induced barrier permeabilization in human umbilical vein endothelial cells and their immortalized hybridoma line, EA.hy926. We found that the vitamin fully prevented increased permeability to the polysaccharide inulin by thrombin in a dose-dependent manner, and it took effect both before and after subjection to thrombin. Thrombin exposure consumed intracellular ascorbate but not the endogenous antioxidant GSH. Likewise, the antioxidants dithiothreitol and tempol did not reverse permeabilization. We identified a novel role for ascorbate in preserving cAMP during thrombin stimulation, resulting in two downstream effects. First, ascorbate maintained the cortical actin cytoskeleton in a Rap1- and Rac1-dependent manner, thus preserving stable adherens junctions between adjacent cells. Second, ascorbate prevented actin polymerization and formation of stress fibers by reducing the activation of RhoA and phosphorylation of myosin light chain. Although ascorbate and thrombin both required calcium for their respective effects, ascorbate did not prevent thrombin permeabilization by obstructing calcium influx. However, preservation of cAMP by ascorbate was found to depend on both the production of nitric oxide by endothelial nitric-oxide synthase, which ascorbate is known to activate, and the subsequent generation cGMP by guanylate cyclase. Together, these data implicate ascorbate in the prevention of inflammatory endothelial barrier permeabilization and explain the underlying signaling mechanism. PMID- 26152731 TI - Recent progress and perspective in JAK inhibitors for rheumatoid arthritis: from bench to bedside. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation and joint destruction. However, the combined use of synthetic disease-modifying anti-rheumatic drug (DMARD) such as methotrexate and a biological DMARD targeting tumour necrosis factor (TNF) has revolutionized treatment of RA. Clinical remission is a realistic target to treat and the maintenance of remission has produced significant improvements in structural and function outcomes. However, biological DMARDs are limited to intravenous or subcutaneous uses and orally available small but strong products have been developed. The multiple cytokines and cell surface molecules bind to receptors, resulting in the activation of various signalling, including phosphorylation of kinase proteins. Among multiple kinases, Janus kinase (JAK) plays pivotal roles in the pathological processes of RA. Tofacitinib, a small product targeting JAK, inhibits phosphorylation of JAK1 and JAK3, subsequent Stat1 and expression of Stat1-inducible genes, which contribute to efficient propagation of its anti inflammatory effects for the treatment of RA. The primary targets of tofacitinib are dendritic cells, CD4(+) T cells such as Th1 and Th17 and activated B cells which leads to multi-cytokine targeting. Six global phase 3 studies revealed that oral administration of 5 or 10 mg tofacitinib was significantly effective than placebo with or without methotrexate in active RA patients with methotrexate naive, inadequately responsive to methotrexate or TNF-inhibitors. Therapeutic efficacy of tofacitinib was observed in a short term after administration and was as strong as adalimumab, a TNF-inhibitor. The most commonly observed adverse events were related to infection, hematologic, hepatic and renal disorders and association of tofacitinib with carcinogenicity and infections remains debated. Further investigation on post-marketing survey would help us understand the positioning of this drug. PMID- 26152730 TI - Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases. AB - The post-translational hydroxylation of prolyl and lysyl residues, as catalyzed by 2-oxoglutarate (2OG)-dependent oxygenases, was first identified in collagen biosynthesis. 2OG oxygenases also catalyze prolyl and asparaginyl hydroxylation of the hypoxia-inducible factors that play important roles in the adaptive response to hypoxia. Subsequently, they have been shown to catalyze N demethylation (via hydroxylation) of N(epsilon)-methylated histone lysyl residues, as well as hydroxylation of multiple other residues. Recent work has identified roles for 2OG oxygenases in the modification of translation-associated proteins, which in some cases appears to be conserved from microorganisms through to humans. Here we give an overview of protein hydroxylation catalyzed by 2OG oxygenases, focusing on recent discoveries. PMID- 26152732 TI - Functional implication of archaeal homologues of human RNase P protein pair Pop5 and Rpp30. AB - PhoPop5 and PhoRpp30 in the hyperthermophilic archaeon Pyrococcus horikoshii, homologues of human ribonuclease P (RNase P) proteins hPop5 and Rpp30, respectively, fold into a heterotetramer [PhoRpp30-(PhoPop5)2-PhoRpp30], which plays a crucial role in the activation of RNase P RNA (PhopRNA). Here, we examined the functional implication of PhoPop5 and PhoRpp30 in the tetramer. Surface plasmon resonance (SPR) analysis revealed that the tetramer strongly interacts with an oligonucleotide including the nucleotide sequence of a stem loop SL3 in PhopRNA. In contrast, PhoPop5 had markedly reduced affinity to SL3, whereas PhoRpp30 had little affinity to SL3. SPR studies of PhoPop5 mutants further revealed that the C-terminal helix (alpha4) in PhoPop5 functions as a molecular recognition element for SL3. Moreover, gel filtration indicated that PhoRpp30 exists as a monomer, whereas PhoPop5 is an oligomer in solution, suggesting that PhoRpp30 assists PhoPop5 in attaining a functionally active conformation by shielding hydrophobic surfaces of PhoPop5. These results, together with available data, allow us to generate a structural and mechanistic model for the PhopRNA activation by PhoPop5 and PhoRpp30, in which the two C terminal helices (alpha4) of PhoPop5 in the tetramer whose formation is assisted by PhoRpp30 act as binding elements and bridge SL3 and SL16 in PhopRNA. PMID- 26152733 TI - Population-based p16 and HPV positivity rates in oropharyngeal cancer in Southeast Scotland. AB - We assessed a population-based cohort of patients diagnosed with oropharyngeal squamous cell carcinoma in Southeast Scotland over 13 months. p16 and human papilloma virus (HPV) expression were determined, and correlated with stage, treatment, smoking and alcohol history, and disease outcomes. Retrospective analysis was performed on 60 patients. p16 immunohistochemistry and HPV genotyping were performed on formalin-fixed paraffin-embedded tissues. HPV infection (as defined by p16 positivity and/or HPV PCR positivity) was identified in 57% of samples, while dual positives were detected in 45% of cases. HPV16 was most prevalent of the HPV types and was associated with 90% of positive samples. Cause-specific 1-year and 2-year survivals were 82.5% and 78.2%, respectively. The p16-positive and HPV-positive groups demonstrated significantly increased cause-specific survival in comparison with their negative counterparts. PMID- 26152734 TI - Non-infectious aortitis of the ascending aorta: a histological and clinical correlation of 71 cases including overlap with medial degeneration and atheroma- a challenge for the pathologist. AB - AIMS: Aortitis is a rare but important cause of thoracic aortic disease. We describe its histopathological patterns and associations with other aortic pathologies and systemic inflammatory disease. METHODS: Database searches of thoracic specimens over 17 years from two centres yielded 71 cases of non infectious aortitis. Histological verification of tunica media inflammation was required for inclusion. Clinical information and histopathological features were recorded. RESULTS: Three histological patterns emerged--necrotising aortitis with giant cells (53), diffuse band-like aortitis (16) and 'other' (2). 50/53 cases of necrotising aortitis with giant cells were isolated/idiopathic, while 9/16 cases of diffuse aortitis had a systemic inflammatory disease. Medial degeneration (MD) was prominent in 23/71 cases--all in the necrotising aortitis with giant cells category. CONCLUSIONS: Non-infectious aortitis is predominantly idiopathic/isolated in nature, occurring in elderly females. Two patterns emerge- (1) necrotising aortitis with giant cells, which is more likely to be idiopathic and linked to MD, suggesting a possible aetiological relationship; and (2) diffuse aortitis, which is linked to an increased risk of systemic inflammatory disease. Knowledge, therefore, of histopathological patterns may guide patient management and follow-up. PMID- 26152735 TI - Resource distribution in neonatology: beyond the Pareto principle. PMID- 26152736 TI - From air to land: understanding water resources through plant-based multidisciplinary research. AB - Current global challenges require solutions that cannot be delivered by any one field alone. New developments in the analysis and interpretation of plant-derived climatic records bridge traditional disciplines, advancing understanding of phenomena of great ecological and societal significance, specifically, those related to changes in the terrestrial water cycle. PMID- 26152737 TI - Feasibility of a practical nurse administered risk assessment tool for drug related problems in home care. AB - AIM: To evaluate feasibility of a practical nurse-administered Drug-related Problem Risk Assessment Tool among home care clients ?65 years. METHODS: Altogether, 36 practical nurses participated in the study. They were trained about the purpose and use of the tool. The training consisted of a day long interactive workshop and involved reviewing four self-selected clients' medications using the tool (one as a pre-assignment before and three as post assignments after the workshop). The data of this study were collected during the training. Triangulation, i.e. combination of methods and data, was used to evaluate the feasibility of the tool. Quantitative data were gathered from returned post-assignment tools and qualitative data from face-to-face discussions and open questions in feedback forms the practical nurses returned after the training. RESULTS: Practical nurses spent 10-45 minutes reviewing one client's medication using the tool (mean 20+/-8). They identified reliably 88% of the risk medicines used by the clients listed in the tool. Of the respondents (n=23) of the feedback forms, 43% reported that they felt it easy or quite easy to answer the questions of the tool. Generic names of medicines, time constraints, home care workers'/client's lack of interest to client's pharmacotherapy and short client contacts were the most common barriers to use the tool. CONCLUSIONS: The Drug-Related Problem Risk Assessment Tool turned out to be feasible among practical nurses. The brief training on the content and use of the tool seems to be sufficient for ensuring reliable use of the tool. PMID- 26152738 TI - Combining an Aurora Kinase Inhibitor and a Death Receptor Ligand/Agonist Antibody Triggers Apoptosis in Melanoma Cells and Prevents Tumor Growth in Preclinical Mouse Models. AB - PURPOSE: Preclinical studies show that inhibition of aurora kinases in melanoma tumors induces senescence and reduces tumor growth, but does not cause tumor regression. Additional preclinical models are needed to identify agents that will synergize with aurora kinase inhibitors to induce tumor regression. EXPERIMENTAL DESIGN: We combined treatment with an aurora kinase A inhibitor, MLN8237, with agents that activate death receptors (Apo2L/TRAIL or death receptor 5 agonists) and monitored the ability of this treatment to induce tumor apoptosis and melanoma tumor regression using human cell lines and patient-derived xenograft (PDX) mouse models. RESULTS: We found that this combined treatment led to apoptosis and markedly reduced cell viability. Mechanistic analysis showed that the induction of tumor cell senescence in response to the AURKA inhibitor resulted in a decreased display of Apo2L/TRAIL decoy receptors and increased display of one Apo2L/TRAIL receptor (death receptor 5), resulting in enhanced response to death receptor ligand/agonists. When death receptors were activated in senescent tumor cells, both intrinsic and extrinsic apoptotic pathways were induced independent of BRAF, NRAS, or p53 mutation status. Senescent tumor cells exhibited BID-mediated mitochondrial depolarization in response to Apo2L/TRAIL treatment. In addition, senescent tumor cells had a lower apoptotic threshold due to decreased XIAP and survivin expression. Melanoma tumor xenografts of one human cell line and one PDX displayed total blockage of tumor growth when treated with MLN8237 combined with DR5 agonist antibody. CONCLUSIONS: These findings provide a strong rationale for combining senescence-inducing therapeutics with death receptor agonists for improved cancer treatment. PMID- 26152739 TI - Molecular Pathways: Is AMPK a Friend or a Foe in Cancer? AB - The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status expressed in essentially all eukaryotic cells. Once activated by energetic stress via a mechanism that detects increases in AMP:ATP and ADP:ATP ratios, AMPK acts to restore energy homeostasis by switching on catabolic pathways that generate ATP, while switching off ATP-consuming processes, including anabolic pathways required for cell growth and proliferation. AMPK activation promotes the glucose sparing, oxidative metabolism utilized by most quiescent cells, rather than the rapid glucose uptake and glycolysis used by most proliferating cells. Numerous pharmacologic activators of AMPK are known, including drugs in long use such as salicylate and metformin, and there is evidence that regular use of either of the latter provides protection against development of cancer. Tumor cells appear to be under selection pressure to downregulate AMPK, thus limiting its restraining influence on cell growth and proliferation, and several interesting mechanisms by which this occurs are discussed. Paradoxically, however, a complete loss of AMPK function, which appears to be rare in human cancers, may be deleterious to survival of tumor cells. AMPK can therefore be either a friend or a foe in cancer, depending on the context. PMID- 26152740 TI - Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay. AB - PURPOSE: Most hormone receptor (HR)(+)/HER2(-) breast cancer patients respond unfavorably to neoadjuvant chemotherapy (NAC); however, genomic tests may identify those patients who are likely to benefit. Using the Prosigna assay, we first evaluated the technical performance of core needle biopsy (CNB) tissues. We then determined whether Prosigna risk of relapse (ROR) score and intrinsic subtype predicted response to NAC in HR(+)/HER2(-) patients using CNB samples. EXPERIMENTAL DESIGN: Using the NanoString's nCounter Dx analysis system and a development tissue sample set, we established tissue requirements and assay output variance. We then evaluated the concordance in subtype and correlation in ROR between CNBs and corresponding surgical resection specimens (SRS) in a second independent sample set. Finally, we analyzed 180 independent CNB samples from HR(+)/HER2(-) patients who were treated with NAC and correlated ROR and intrinsic subtype with pathologic response. RESULTS: Intra- and interbiopsy variabilities were 2.2 and 6.8 ROR units, respectively. Subtype concordance within multiple CNBs was high for the 4- and 3-subtype classifications (k = 0.885 and 0.889, respectively). Correlation in Prosigna ROR score observed between paired CNBs and SRS was high (r >= 0.90), and subtype concordance was also high for the 4- and 3 subtype classifications (kappa = 0.81 and 0.91, respectively). Prosigna results obtained from the HR(+)/HER2(-) patient samples showed that both ROR (P = 0.047) and intrinsic subtype (OR LumA vs. non-LumA = 0.341, P = 0.037) were significant predictors of response to NAC. CONCLUSIONS: Prosigna ROR and intrinsic subtype are readily obtained from CNB samples in normal practice and reliably predict response to NAC in HR(+)/HER2(-) patients. PMID- 26152741 TI - Moving Beyond "Lumpology": PET/CT Imaging of Pheochromocytoma and Paraganglioma. AB - High somatostatin receptor expression on the cell membrane of succinate dehydrogenase mutation-related pheochromocytoma and paraganglioma provides a potential target for imaging and therapy. (68)Ga-DOTATATE positron emission PET/CT may represent a new gold standard for staging pheochromocytoma/paraganglioma and have future therapeutic implications. PMID- 26152743 TI - Stool Bacteriomic Profiling in Patients with Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitors. AB - PURPOSE: Diarrhea occurs in approximately half of patients with metastatic renal cell carcinoma (mRCC) receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI). We evaluated the relationship between VEGF-TKI related diarrhea and stool microbiota. EXPERIMENTAL DESIGN: Stool samples were collected from 20 mRCC patients receiving VEGF-TKIs. 16S rRNA sequencing was used to characterize the stool bacteriomic profiling of patients. Assay validation with Salmonella typhimurium spike-in experiments suggested greatest speciation with use of the V5 region. RESULTS: Higher levels of Bacteroides spp. and lower levels of Prevotella spp. were found in patients with diarrhea. In addition, patients receiving VEGF-TKIs with mRCC appeared to have less relative abundance of Bifidobacterium spp. as compared with previous reports based on healthy subjects. CONCLUSIONS: We have thus demonstrated interplay between microbiota and VEGF-TKI-induced diarrhea. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in VEGF-TKI-related diarrhea. PMID- 26152744 TI - Late-Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337). AB - PURPOSE: Immunotherapy as a treatment for cancer holds the promise of complete and durable tumor remission, yet the immunosuppressive environment created by many tumors, advanced patient age, and previous treatments with cytotoxic agents may limit the approach. The activity of motolimod (VTX-2337), a potent and selective Toll-like receptor 8 (TLR8) agonist, was therefore assessed in the context of advanced, late-stage cancer patients. EXPERIMENTAL DESIGN: The repertoire of mediators induced from human peripheral blood mononuclear cells in response to motolimod was characterized. Translational studies in cynomolgus monkeys elucidated the activity of motolimod on an intact immune system, identified biomarkers of TLR8 activation, and defined the relationship between the pharmacokinetic and pharmacodynamic (PK/PD) response. The PK/PD relationship for motolimod in cancer patients was assessed, compared with preclinical findings, and contrasted with activity in healthy volunteers. RESULTS: In late stage cancer patients, plasma levels of multiple biomarkers, including IL6, G CSF, MCP-1, and MIP1-beta, increased with increasing motolimod dose. The magnitude and breadth of the biomarker response closely aligned with the response seen in preclinical studies, demonstrating that advanced cancer patients remained responsive to TLR8 activation. In addition, the PK/PD response in cancer patients closely aligned with the activity of motolimod seen in healthy volunteers. CONCLUSIONS: Late-stage cancer patients are highly sensitive to TLR8 activation by motolimod. Tumor burden, advanced age, and prior treatment history with cytotoxic agents did not moderate or modify the response predicted by nonclinical studies and confirmed in healthy volunteers. Clin Cancer Res; 21(24); 5445-52. (c)2015 AACR. PMID- 26152746 TI - Estimating negative likelihood ratio confidence when test sensitivity is 100%: A bootstrapping approach. AB - Objectives Assessing high-sensitivity tests for mortal illness is crucial in emergency and critical care medicine. Estimating the 95% confidence interval (CI) of the likelihood ratio (LR) can be challenging when sample sensitivity is 100%. We aimed to develop, compare, and automate a bootstrapping method to estimate the negative LR CI when sample sensitivity is 100%. Methods The lowest population sensitivity that is most likely to yield sample sensitivity 100% is located using the binomial distribution. Random binomial samples generated using this population sensitivity are then used in the LR bootstrap. A free R program, "bootLR," automates the process. Extensive simulations were performed to determine how often the LR bootstrap and comparator method 95% CIs cover the true population negative LR value. Finally, the 95% CI was compared for theoretical sample sizes and sensitivities approaching and including 100% using: (1) a technique of individual extremes, (2) SAS software based on the technique of Gart and Nam, (3) the Score CI (as implemented in the StatXact, SAS, and R PropCI package), and (4) the bootstrapping technique. Results The bootstrapping approach demonstrates appropriate coverage of the nominal 95% CI over a spectrum of populations and sample sizes. Considering a study of sample size 200 with 100 patients with disease, and specificity 60%, the lowest population sensitivity with median sample sensitivity 100% is 99.31%. When all 100 patients with disease test positive, the negative LR 95% CIs are: individual extremes technique (0,0.073), StatXact (0,0.064), SAS Score method (0,0.057), R PropCI (0,0.062), and bootstrap (0,0.048). Similar trends were observed for other sample sizes. Conclusions When study samples demonstrate 100% sensitivity, available methods may yield inappropriately wide negative LR CIs. An alternative bootstrapping approach and accompanying free open-source R package were developed to yield realistic estimates easily. This methodology and implementation are applicable to other binomial proportions with homogeneous responses. PMID- 26152745 TI - Pyrvinium Targets CD133 in Human Glioblastoma Brain Tumor-Initiating Cells. AB - PURPOSE: Clonal evolution of cancer may be regulated by determinants of stemness, specifically self-renewal, and current therapies have not considered how genetic perturbations or properties of stemness affect such functional processes. Glioblastoma-initiating cells (GICs), identified by expression of the cell surface marker CD133, are shown to be chemoradioresistant. In the current study, we sought to elucidate the functional role of CD133 in self-renewal and identify compounds that can specifically target this CD133(+) treatment-refractory population. EXPERIMENTAL DESIGN: Using gain/loss-of-function studies for CD133 we assessed the in vitro self-renewal and in vivo tumor formation capabilities of patient-derived glioblastoma cells. We generated a CD133 signature combined with an in silico screen to find compounds that target GICs. Self-renewal and proliferation assays on CD133-sorted samples were performed to identify the preferential action of hit compounds. In vivo efficacy of the lead compound pyrvinium was assessed in intracranial GIC xenografts and survival studies. Lastly, microarray analysis was performed on pyrvinium-treated GICs to discover core signaling events involved. RESULTS: We discovered pyrvinium, a small molecule inhibitor of GIC self-renewal in vitro and in vivo, in part through inhibition of Wnt/beta-catenin signaling and other essential stem cell regulatory pathways. We provide a therapeutically tractable strategy to target self renewing, chemoradioresistant, and functionally important CD133(+) stem cells that drive glioblastoma relapse and mortality. CONCLUSIONS: Our study provides an integrated approach for the eradication of clonal populations responsible for cancer progression, and may apply to other aggressive and heterogeneous cancers. PMID- 26152747 TI - Global tests for novelty. AB - Outlier detection covers the wide range of methods aiming at identifying observations that are considered unusual. Novelty detection, on the other hand, seeks observations among newly generated test data that are exceptional compared with previously observed training data. In many applications, the general existence of novelty is of more interest than identifying the individual novel observations. For instance, in high-throughput cancer treatment screening experiments, it is meaningful to test whether any new treatment effects are seen compared with existing compounds. Here, we present hypothesis tests for such global level novelty. The problem is approached through a set of very general assumptions, making it innovative in relation to the current literature. We introduce test statistics capable of detecting novelty. They operate on local neighborhoods and their null distribution is obtained by the permutation principle. We show that they are valid and able to find different types of novelty, e.g. location and scale alternatives. The performance of the methods is assessed with simulations and with applications to real data sets. PMID- 26152748 TI - Mycobacterial cervicofacial lymphadenitis in human immunodeficiency virus infected individuals after antiretroviral therapy initiation. AB - OBJECTIVES/HYPOTHESIS: Mycobacterial infections are the leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals worldwide. Cervical lymph nodes are the most frequently affected extrapulmonary sites. Despite the substantial reduction in complications of HIV tuberculosis coinfection, a proportion of individuals develop immune reconstitution inflammatory syndrome (IRIS), a term used for a clinical deterioration following initiation of antiretroviral therapy (ART). The objective of this study was to describe mycobacterial-associated IRIS in cervical lymph nodes of HIV-infected individuals receiving ART. STUDY DESIGN: Retrospective cohort study, set in a tertiary referral center in Mexico City. METHODS: We included ART-naive subjects who had at least one follow-up ear, nose, and throat examination, and were diagnosed with lymph node mycobacterial infection before or during the first 3 months of ART initiation. Mycobacterial-associated IRIS in cervical lymph nodes was determined retrospectively through clinical case definition and medical chart review. RESULTS: Thirty-three subjects who initiated ART were diagnosed with cervical lymph node mycobacteriosis; 24 had Mycobacterium tuberculosis infection and nine had nontuberculous disease. CONCLUSIONS: M. tuberculosis was the most common pathogen isolated from cervical lymph nodes. The only factor associated with IRIS was infection with a nontuberculous mycobacteria. The unexpectedly high incidence of mycobacterial-associated IRIS underlines the relevance of head and neck examination before ART initiation. LEVEL OF EVIDENCE: 4. PMID- 26152742 TI - Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium. AB - PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with >= 4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. RESULTS: Five SNPs were significantly associated (P <= 1.0 * 10(-5)) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P <= 7.1 * 10(-6)). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA <= 6 * 10(-3)). CONCLUSIONS: We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies. PMID- 26152749 TI - Hypofractionated Helical Tomotherapy for Older Aged Patients With Prostate Cancer: Preliminary Results of a Phase I-II Trial. AB - In our center, the feasibility and related acute toxicities of hypofractionated helical tomotherapy have been evaluated in older aged patients with prostate cancer . Between February 2009 and February 2014, 67 patients (older than 65 years) were enrolled in a prospective phase I-II study (registered number, ChiCTR ONC-13004037). Patients in cohort 1 (n = 33) and cohort 2 (n = 34) received 76 Gy in 34 fractions (2.25 Gy/F) and 71.6 Gy in 28 fractions (2.65 Gy/F), respectively, to the prostate and seminal vesicles, while 25 patients in cohort 2 also received integrated elective lymph node irradiation (50.4 Gy). All patients were treated with helical tomotherapy, and daily image guidance was performed before each treatment. Acute toxicities were assessed with Radiation Therapy Oncology Group (RTOG)/European Organization for Research on Treatment of Cancer (EORTC) criteria. No significant difference was detected between the 2 cohorts in the incidence of acute toxicities. In cohort 1, the incidences of grade 1 and 2 genitourinary and gastrointestinal toxicities were 45.5% and 45.4%, respectively, and without grade 3 and 4 toxicities. In cohort 2, the incidences of acute grade 1 and 2 genitourinary and gastrointestinal toxicities were 47.1% and 55.9%, respectively, and grade 3 genitourinary toxicity (hematuria) was noted only in 1 patient. No significant difference was detected in the incidence of acute toxicities between the patients receiving integrated elective lymph node irradiation and those receiving irradiation to prostate and seminal vesicle in cohort 2. Univariate and multivariate analyses were performed with clinical parameters. Only the baseline weight was found negatively correlated with genitourinary toxicities at a weak level (relative risk = 0.946, 95% confidence interval 0.896-0.998], P = .043). This study shows that 2 hypofractionation regimens (76 Gy/34F and 71.6 Gy/28F) delivered with HT are well tolerated in older aged patients having prostate cancer without significant difference for acute toxicities between the 2 cohorts. Late toxicities and treatment outcomes for these patients are under investigation. PMID- 26152750 TI - Evaluation of Photoneutron Dose Measured by Bubble Detectors in Conventional Linacs and Cyberknife Unit: Effective Dose and Secondary Malignancy Risk Estimation. AB - This study aims to reduce the uncertainty about the photoneutron dose produced over a course of radiotherapy with high-energy photon beams and evaluate photoneutron contamination-based secondary malignancy risk for different treatment modalities. Dosimetric measurements were taken in Philips SL25/75, Elekta Synergy Platform (Elekta AB, Stockholm, Sweden), Varian Clinac DHX High Performance systems (Varian Medical Systems, Palo Alto, CA), and Cyberknife Robotic Radiosurgery Unit (Accuray Inc., Sunnyvale, CA) using bubble detector for neutron dosimetry. The measurement data were used to determine in-field and out of-field neutron equivalent dose in 6-MV 3D conformal radiotherapy, sliding window-intensity-modulated radiotherapy, and stereotactic body radiotherapy and to calculate the effective dose in 18-MV 3D conformal radiotherapy and sliding window-intensity-modulated radiotherapy techniques for patients with prostate cancer undergoing a standard treatment. For the 18-MV treatment techniques, the secondary malignancy risk due to the neutron contamination was estimated using the risk factors published by The International Commission on Radiological Protection. The neutron contamination-based secondary malignancy risk for the 18 MV 3D conformal radiotherapy and sliding window-intensity-modulated radiotherapy modalities was found to be 0.44% and 1.45% for Elekta Synergy Platform and 0.92% and 3.0% for the Varian Clinac DHX High Performance, respectively. For 6-MV 3D conformal radiotherapy, sliding window-intensity-modulated radiotherapy, and stereotactic body radiotherapy treatment techniques, neutron equivalent doses inside the treatment field were found to be lower than 40 mSv. Our measurements reveal that equivalent dose and effective dose due to the neutron contamination are at a considerable level for 18-MV sliding window-intensity-modulated radiotherapy treatments, while 6-MV photon beams used in different modalities still induce only negligible photoneutrons. The secondary malignancy risk based on photoneutron should be therefore taken into consideration in case of selecting 18-MV photons in a sliding window-intensity-modulated radiotherapy treatment instead of 6 MV. PMID- 26152751 TI - Reference Change Values for Sodium Are Ignored by the American and European Treatment Guidelines for Hyponatremia. PMID- 26152752 TI - gamma-Glutamyl Transferase Is Associated with Mortality Outcomes Independently of Fatty Liver. AB - BACKGROUND: High serum enzyme activity levels of gamma-glutamyl transferase (GGT) are associated with increased risk of mortality, but whether this is mediated by fatty liver, as a common cause of high GGT levels, is uncertain. Our aim was to test whether GGT levels are associated with all-cause, cancer, and cardiovascular (CVD) mortality, independently of fatty liver. METHODS: In an occupational cohort (n = 278 419), causes of death (International Statistical Classification of Diseases and Related Health Problems, 10th revision) were recorded over 7 years. Liver function tests and liver fat [measured by ultrasonographic standard criteria or fatty liver index (FLI)] were assessed at baseline. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% CIs of all-cause, cancer, and CVD mortality for GGT quartiles (with lowest GGT quartile as reference). RESULTS: There were 136, 167, 265, and 342 deaths across increasing GGT quartiles. After adjusting for liver fat (by ultrasound diagnosis) in the fully adjusted model, all-cause and cancer mortality were increased in the highest GGT quartile [HR 1.50 (95% CI 1.15-1.96) and 1.57 (1.05-2.35), respectively]. For CVD mortality, the hazard was attenuated: HR 1.35 (95% CI 0.72 2.56). After adjusting for FLI in the fully adjusted model, HRs for all-cause, cancer, and CVD mortality were 1.46 (0.72-2.56), 2.03 (1.02-4.03), and 1.16 (0.41,3.24), respectively. CONCLUSIONS: There were similar hazards for all-cause and cancer mortality and attenuated hazards for CVD mortality for people in the highest GGT quartile, adjusting for fatty liver assessed by either ultrasound or FLI. PMID- 26152753 TI - Disruptive Innovation in Laboratory Medicine. PMID- 26152755 TI - Erratum for Jiang et al., Zoonotic and Potentially Host-Adapted Enterocytozoon bieneusi Genotypes in Sheep and Cattle in Northeast China and an Increasing Concern about the Zoonotic Importance of Previously Considered Ruminant-Adapted Genotypes. PMID- 26152757 TI - Guiding Hypertension Management Using Central Blood Pressure: Effect of Medication Withdrawal on Left Ventricular Function. AB - BACKGROUND: Central blood pressure (BP) is an acknowledged contributor to end organ damage and independent determinant of prognosis. Primary analysis from the BPGUIDE study demonstrated no detriment on left ventricular (LV) structure from central BP-guided hypertension management, despite significant medication withdrawal. However, the effect of this on LV function has not been investigated. In this study, we sought to investigate the impact of central BP-guided hypertension management on LV systolic and diastolic performance. METHODS: A total of 286 enrollees with uncomplicated hypertension were randomized to therapeutic decisions guided by best-practice usual care (UC) or, in addition, by central BP intervention (CBP) for 12 months. Each participant underwent baseline and follow-up 2-dimensional echocardiography, with assessment undertaken by an expert blinded to participant allocation. RESULTS: Antihypertensive medication quantity remained unchanged for UC but significantly decreased with intervention. However, no significant between-group differences were noted for changes during follow-up in both brachial and central BP, as well as other central hemodynamic parameters: augmentation index and augmented pressure. Similarly, there were no differences between groups in parameters of LV diastolic function: tissue e' velocity (?UC vs. ?CBP; P = 0.27) and E/e' ratio (?UC vs. ?CBP; P = 0.60), and systolic parameters: LV longitudinal strain (?UC vs. ?CBP; P = 0.55), circumferential strain (?UC vs. ?CBP; P = 0.79), and ejection fraction (?UC vs. ?CBP; P = 0.15). CONCLUSIONS: Hypertension management guided by central BP, resulting in significant withdrawal of medication to maintain appropriate BP control, had no adverse effect on LV systolic or diastolic function. Clinical trials registration: Australia New Zealand Clinical Trial Registry Number ACTRN12608 000041358. PMID- 26152758 TI - Boron-Catalyzed Silylative Reduction of Nitriles in Accessing Primary Amines and Imines. AB - Silylative reduction of nitriles was studied under transition metal-free conditions by using B(C6F5)3 as a catalyst with hydrosilanes as a reductant. Alkyl and (hetero)aryl nitriles were efficiently converted to primary amines or imines under mild conditions. The choice of silanes was found to determine the selectivity: while a full reduction of nitriles was highly facile, the use of sterically bulky silanes allowed for the partial reduction leading to N silylimines. PMID- 26152759 TI - What pilot studies tell us! PMID- 26152760 TI - AJMQ newsletter: an update from the leadership of the American College of Medical Quality. PMID- 26152761 TI - Responses of seagrass to anthropogenic and natural disturbances do not equally translate to its consumers. AB - Coastal communities are under threat from many and often co-occurring local (e.g., pollution, eutrophication) and global stressors (e.g., climate change), yet understanding the interactive and cumulative impacts of multiple stressors in ecosystem function is far from being accomplished. Ecological redundancy may be key for ecosystem resilience, but there are still many gaps in our understanding of interspecific differences within a functional group, particularly regarding response diversity, that is, whether members of a functional group respond equally or differently to anthropogenic stressors. Herbivores are critical in determining plant community structure and the transfer of energy up the food web. Human disturbances may alter the ecological role of herbivory by modifying the defense strategies of plants and thus the feeding patterns and performance of herbivores. We conducted a suite of experiments to examine the independent and interactive effects of anthropogenic (nutrient and CO2 additions) and natural (simulated herbivory) disturbances on a seagrass and its interaction with two common generalist consumers to understand how multiple disturbances can impact both a foundation species and a key ecological function (herbivory) and to assess the potential existence of response diversity to anthropogenic and natural changes in these systems. While all three disturbances modified seagrass defense traits, there were contrasting responses of herbivores to such plant changes. Both CO2 and nutrient additions influenced herbivore feeding behavior, yet while sea urchins preferred nutrient-enriched seagrass tissue (regardless of other experimental treatments), isopods were deterred by these same plant tissues. In contrast, carbon enrichment deterred sea urchins and attracted isopods, while simulated herbivory only influenced isopod feeding choice. These contrasting responses of herbivores to disturbance-induced changes in seagrass help to better understand the ecological functioning of seagrass ecosystems in the face of human disturbances and may have important implications regarding the resilience and conservation of these threatened ecosystems. PMID- 26152763 TI - A low-protein diet combined with low-dose endotoxin leads to changes in glucose homeostasis in weanling rats. AB - Severe malnutrition is a leading cause of global childhood mortality, and infection and hypoglycemia or hyperglycemia are commonly present. The etiology behind the changes in glucose homeostasis is poorly understood. Here, we generated an animal model of severe malnutrition with and without low-grade inflammation to investigate the effects on glucose homeostasis. Immediately after weaning, rats were fed diets containing 5 [low-protein diet (LP)] or 20% protein [control diet (CTRL)], with or without repeated low-dose intraperitoneal lipopolysaccharide (LPS; 2 mg/kg), to mimic inflammation resulting from infections. After 4 wk on the diets, hyperglycemic clamps or euglycemic hyperinsulinemic clamps were performed with infusion of [U-(13)C6]glucose and [2 (13)C]glycerol to assess insulin secretion, action, and hepatic glucose metabolism. In separate studies, pancreatic islets were isolated for further analyses of insulin secretion and islet morphometry. Glucose clearance was reduced significantly by LP feeding alone (16%) and by LP feeding with LPS administration (43.8%) compared with control during the hyperglycemic clamps. This was associated with a strongly reduced insulin secretion in LP-fed rats in vivo as well as ex vivo in islets but signficantly enhanced whole body insulin sensitivity. Gluconeogenesis rates were unaffected by LP feeding, but glycogenolysis was higher after LP feeding. A protein-deficient diet in young rats leads to a susceptibility to low-dose endotoxin-induced impairment in glucose clearance with a decrease in the islet insulin secretory pathway. A protein-deficient diet is associated with enhanced peripheral insulin sensitivity but impaired insulin-mediated suppression of hepatic glycogenolysis. PMID- 26152762 TI - Epstein-Barr virus in the enlarged salivary tissues of patients with IgG4-related disease. AB - OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease entity characterized by high-serum IgG4 concentration and IgG4-producing plasma cell production with fibrotic or sclerotic changes in affected organs. We aimed to clarify the roles of Epstein-Barr virus (EBV) in patients with IgG4-RDs. STUDY DESIGN AND SETTING: A retrospective clinical study at the Yamagata University School of Medicine, Yamagata, Japan. METHODS: The patient group consisted of four males and four females with an average age of 62 years (range: 48-73). Expression of IgG4, latent member protein 1, EBV nuclear antigens-2, and EBV-encoded RNA in affected salivary glands from patients with IgG4-RD was examined by using immunohistochemistry and in situ hybridization. The copy number of EBV DNA in the salivary glands was also investigated by real-time polymerase chain reaction. RESULTS: All patients had hard masses in the salivary or lacrimal glands, or both, bilaterally. Serum concentrations of IgG4 were elevated in all cases (mean 589.1, range 129-1750), and IgG4-positive plasmacytes were observed in the involved salivary glands. Four patients developed potentially life threatening systemic involvement after initial salivary gland swelling. EBV associated molecules (EBNA and EBER) were overexpressed in the affected salivary glands. The copy number of EBV DNA was significantly higher in patients with potentially life-threatening systemic involvement than in patients without systemic involvement (P < 0.05). CONCLUSION: These results suggest that the copy number of EBV DNA could be useful as diagnostic findings in IgG4-RD to predict potentially life-threatening systemic involvement. LEVEL OF EVIDENCE: 4. PMID- 26152764 TI - The impact of delivery profile of essential amino acids upon skeletal muscle protein synthesis in older men: clinical efficacy of pulse vs. bolus supply. AB - Essential amino acids (EAA) are responsible for skeletal muscle anabolic effects after nutrient intake. The pattern of appearance of EAA in blood, e.g., after intake of "slow" or "fast" protein sources or in response to grazing vs. bolus feeding patterns, may impact anabolism. However, the influence of this on muscle anabolism is poorly understood, particularly in older individuals. We determined the effects of divergent feeding profiles of EAA on blood flow, anabolic signaling, and muscle protein synthesis (MPS) in older men. Sixteen men (~70 yr) consumed EAA either as a single dose (bolus, 15 g; n = 8) or as small repeated fractions (pulse, 4 * 3.75 g every 45 min; n = 8) during (13)C6 phenylalanine infusion. Repeated blood samples and muscle biopsies permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling, and MPS. Muscle blood flow was assessed by contrast-enhanced ultrasound (Sonovue). Bolus achieved rapid insulinemia (12.7 MUiU/ml 25-min postfeed), essential aminoacidemia (~3,000 MUM, 45-65 min postfeed), and mTORC1 activity; pulse achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (~1,800 MUM 80-195 min after feeding), and undetectable mTORC1 signaling. Despite this, equivalent anabolic responses were observed: fasting FSRs of 0.051 and 0.047%/h (bolus and pulse, respectively) increased to 0.084 and 0.073%/h, respectively. Moreover, pulse led to sustainment of MPS beyond 180 min, when bolus MPS had returned to basal rates. We detected no benefit of rapid aminoacidemia in this older population despite enhanced anabolic signaling and greater overall EAA exposure. Rather, apparent delayed onset of the "muscle-full" effect permitted identical MPS following low amplitude-sustained EAA exposure. PMID- 26152765 TI - Proopiomelanocortin, agouti-related protein, and leptin in human cerebrospinal fluid: correlations with body weight and adiposity. AB - Leptin and its neuronal targets, which produce proopiomelanocortin (POMC) and agouti-related protein (AgRP), regulate energy balance. This study characterized leptin, POMC, and AgRP in the cerebrospinal fluid (CSF) of 47 healthy human subjects, 23 lean and 24 overweight/obese (OW/OB), as related to BMI, adiposity, plasma leptin, soluble leptin receptor (s-OB-R), and insulin. POMC was measured since the POMC prohormone is the predominant POMC peptide in CSF and correlates with hypothalamic POMC in rodents. Plasma AgRP was similarly characterized. CSF leptin was 83-fold lower than in plasma and correlated strongly with BMI, body fat, and insulin. The relative amount of leptin transported into CSF declined with increasing BMI, ranging from 4.5 to 0.52%, consistent with a saturable transport mechanism. CSF sOB-R was 78-fold lower than in plasma and correlated negatively with plasma and CSF leptin. CSF POMC was higher in lean vs. OW/OB subjects (P < 0.001) and correlated negatively with CSF leptin (r = -0.60, P < 0.001) and with plasma leptin, insulin, BMI, and adiposity. CSF AgRP was not different in lean vs. OW/OB; however, plasma AgRP was higher in lean subjects (P = 0.001) and correlated negatively with BMI, adiposity, leptin, insulin, and HOMA (P < 0.005). Thus, CSF measurements may provide useful biomarkers for brain leptin and POMC activity. The striking negative correlation between CSF leptin and POMC could be secondary to leptin resistance and/or neuronal changes associated with obesity but may also indicate that POMC plays a primary role in regulating body weight and adiposity. The role of plasma AgRP as a neuroendocrine biomarker deserves further study. PMID- 26152766 TI - Glucagon sensitivity and clearance in type 1 diabetes: insights from in vivo and in silico experiments. AB - Glucagon use in artificial pancreas for type 1 diabetes (T1D) is being explored for prevention and rescue from hypoglycemia. However, the relationship between glucagon stimulation of endogenous glucose production (EGP) viz., hepatic glucagon sensitivity, and prevailing glucose concentrations has not been examined. To test the hypothesis that glucagon sensitivity is increased at hypoglycemia vs. euglycemia, we studied 29 subjects with T1D randomized to a hypoglycemia or euglycemia clamp. Each subject was studied at three glucagon doses at euglycemia or hypoglycemia, with EGP measured by isotope dilution technique. The peak EGP increments and the integrated EGP response increased with increasing glucagon dose during euglycemia and hypoglycemia. However, the difference in dose response based on glycemia was not significant despite higher catecholamine concentrations in the hypoglycemia group. Knowledge of glucagon's effects on EGP was used to develop an in silico glucagon action model. The model derived output fitted the obtained data at both euglycemia and hypoglycemia for all glucagon doses tested. Glucagon clearance did not differ between glucagon doses studied in both groups. Therefore, the glucagon controller of a dual hormone control system may not need to adjust glucagon sensitivity, and hence glucagon dosing, based on glucose concentrations during euglycemia and hypoglycemia. PMID- 26152767 TI - Physiology in Medicine: update on lifestyle determinants of postprandial triacylglycerolemia with emphasis on the Mediterranean lifestyle. AB - This review updates the effect of lifestyle on plasma triacylglycerols (TAG) in the postprandial state, commonly reported as postprandial lipemia (PPL), an independent risk factor for cardiovascular diseases (CVD). Numerous studies have shown that Mediterranean diet may reduce PPL. However, most of these studies were focused on the type of fat (i.e., monounsaturated fat from olive oil), and the other components of the Mediterranean lifestyle were neglected. Physical activity, an integral part of this lifestyle, is widely investigated on its own and shown to reduce PPL. In addition, preliminary results of studies examining other Mediterranean "ingredients", such as legumes, fish, and herbs, showed additional benefits; however, data on the long-term effects are limited. More studies are needed to confirm short-term results and investigate the effects of the whole Mediterranean lifestyle on PPL and whether these effects mediate its protective role on CVD. Moreover, investigation of the effects in nonhealthy populations and the underlying mechanisms would be clinically helpful in individualizing the appropriate intervention. PMID- 26152768 TI - [Analysis of patient complaints in Primary Care: An opportunity to improve clinical safety]. AB - OBJECTIVE: To determine the prevalence and type of the clinical safety problems contained in the complaints made by patients and users in Primary Care. MATERIAL AND METHODS: An observational, descriptive, cross-sectional study was conducted by analysing both the complaint forms and the responses given to them in the period of one year. RESULTS: At least 4.6% of all claims analysed in this study contained clinical safety problems. The family physician is the professional who received the majority of the complaints (53.6%), and the main reason was the problems related to diagnosis (43%), mainly the delay in diagnosis. Other variables analysed were the severity of adverse events experienced by patients (in 68% of cases the patient suffered some harm), the subsequent impact on patient care, which was affected in 39% of cases (7% of cases even requiring hospital admission), and the level of preventability of adverse events (96% avoidable) described in the claims. Finally the type of response issued to each complaint was analysed, being purely bureaucratic in 64% of all cases. CONCLUSIONS: Complaints are a valuable source of information about the deficiencies identified by patients and healthcare users. There is considerable scope for improvement in the analysis and management of claims in general, and those containing clinical safety issues in particular. To date, in our area, there is a lack of appropriate procedures for processing these claims. Likewise, we believe that other pathways or channels should be opened to enable communication by patients and healthcare users. PMID- 26152769 TI - Agrobacterium-mediated in planta genetic transformation of sugarcane setts. AB - KEY MESSAGE: An efficient, reproducible, and genotype-independent in planta transformation has been developed for sugarcane using setts as explant. Traditional Agrobacterium-mediated genetic transformation and in vitro regeneration of sugarcane is a complex and time-consuming process. Development of an efficient Agrobacterium-mediated transformation protocol, which can produce a large number of transgenic plants in short duration is advantageous. Hence, in the present investigation, we developed a tissue culture-independent in planta genetic transformation system for sugarcane using setts collected from 6-month old sugarcane plants. The sugarcane setts (nodal cuttings) were infected with three Agrobacterium tumefaciens strains harbouring pCAMBIA 1301-bar plasmid, and the transformants were selected against BASTA((r)). Several parameters influencing the in planta transformation such as A. tumefaciens strains, acetosyringone, sonication and exposure to vacuum pressure, have been evaluated. The putatively transformed sugarcane plants were screened by GUS histochemical assay. Sugarcane setts were pricked and sonicated for 6 min and vacuum infiltered for 2 min at 500 mmHg in A. tumefaciens C58C1 suspension containing 100 uM acetosyringone, 0.1 % Silwett L-77 showed the highest transformation efficiency of 29.6 % (with var. Co 62175). The three-stage selection process completely eliminated the chimeric transgenic sugarcane plants. Among the five sugarcane varieties evaluated using the standardized protocol, var. Co 6907 showed the maximum transformation efficiency (32.6 %). The in planta transformation protocol described here is applicable to transfer the economically important genes into different varieties of sugarcane in relatively short time. PMID- 26152771 TI - Effect of methylene group insertions on the structural rigidity of Aib containing helices. AB - Nonprotein amino acids are being extensively used in the design of synthetic peptides to create new structure mimics. In this study we report the effect of methylene group insertions in a heptapeptide Boc-Ala1-Leu2-Aib3-Xxx4-Ala5-Leu6 Aib7-OMe which nicely folds into a mixed 310 -/alpha-helical structure when Xxx= Ala. Analogs of this peptide have been made and studied by replacing central Xxx4 residue with Glycine (alpha-residue), beta-Alanine (beta-Alphala), gamma aminobutyric acid (Gaba), and epsilon-aminocaproic acid (epsilon-Aca). NMR and circular dichroism were used to study the solution structure of these peptides. Crystals of the peptides containing alanine, beta-Alphala, and Gaba reveal that increasing the number of central methylene (-CH2 -) groups introduces local perturbations even as the helical structure is retained. PMID- 26152770 TI - Leadership, Organizational Climate, and Perceived Burden of Evidence-Based Practice in Mental Health Services. AB - The use of evidence-based practices (EBPs) is associated with favorable client outcomes, yet perceived burden of using EBPs may affect the adoption and implementation of such practices. Multilevel path analysis was used to examine the associations of transformational leadership with organizational climate, and their associations with perceived burden of using EBPs. Results indicated significant relationships between transformational leadership and empowering and demoralizing climates, and between demoralizing climate and perceived burden of EBPs. We found significant indirect associations of leadership and perceived burden through organizational climate. Findings suggest that further research is needed to examine the extent to which improving leadership and organizational climate may reduce perceived burden and use of EBPs with the ultimate goal of enhancing quality of care. PMID- 26152772 TI - Hypernasality after using the endoscopic endonasal transsphenoidal approach for skull base tumors. AB - OBJECTIVES/HYPOTHESIS: The increasing number of endoscopic endonasal transsphenoidal approaches (EETSA) has resulted in several sinonasal complications, including voice changes. Here, we compared preoperative and postoperative voice changes according to age. METHODS: We retrospectively reviewed the medical records. Patients were divided into the following three groups according to age: <= 30 years, 31 to 60 years, and >= 60 years. Patients underwent preoperative voice evaluation using acoustic analysis, a nasometer, and the voice handicap index (VHI). A nasometer was used to measure the nasalance scores. The subjects read or repeated three speech stimuli. For each stimulus, mean nasalance scores were obtained and age dependence was analyzed. Repeat testing was performed 6 months postoperatively. RESULTS: One hundred and seventy patients who underwent binostril four-hand EETSA with a bilateral modified rescue flap were included in this study. Mean nasalance scores for the oral passage, oronasal passage, and nasal passage--as well as mean jitter scores, shimmer scores, and VHI--were significantly increased in all of the EETSA patients (P < 0.05 for all). Mean nasalance scores for the nasal sentences were significantly increased in the <= 30 age group (all, P < 0.05). Scores for the oronasal passage and nasal passage were significantly increased in the 31 to 60 age group (all, P < 0.05). Scores for the oronasal passage, nasal passage, jitter, and shimmer were significantly increased in the > 60 age group (all, P < 0.05). CONCLUSIONS: Endoscopic endonasal transsphenoidal approaches might contribute to voice changes. In addition, older age might produce hypernasality and roughness after EETSA. Patients who plan to undergo EETSA should be informed that their voice may change after the operation. LEVEL OF EVIDENCE: 4. PMID- 26152773 TI - Acute effects of Finnish sauna and cold-water immersion on haemodynamic variables and autonomic nervous system activity in patients with heart failure. AB - BACKGROUND: The haemodynamic response to Finnish sauna and subsequent cold-water immersion in heart failure patients is unknown. METHODS: Haemodynamic response to two consecutive Finnish sauna (80C) exposures, followed by a final head-out cold water immersion (12C) was measured in 37 male participants: chronic heart failure (n = 12, 61.8 +/- 9.2 years), coronary artery disease (n = 13, 61.2 +/- 10.6 years) and control subjects (n = 12, 60.9 +/- 8.9 years). Cardiac output was measured non-invasively with an inert gas rebreathing method prior to and immediately after the first sauna exposure and after cold-water immersion, respectively. Blood pressure was measured before, twice during and after sauna. The autonomic nervous system was assessed by power spectral analysis of heart rate variability. Total power, low-frequency and high-frequency components were evaluated. The low frequency/high frequency ratio was used as a marker of sympathovagal balance. Sauna and cold-water immersion were well tolerated by all subjects. RESULTS: Cardiac output and heart rate significantly increased in all groups after sauna and cold-water immersion (p < 0.05), except for coronary artery disease patients after sauna exposure. Systolic blood pressure during sauna decreased significantly in all groups with a nadir after 6 min (all p < 0.05). Cold-water immersion significantly increased systolic blood pressure in all groups (p < 0.05). No change in the low/high frequency ratio was found in chronic heart failure patients. In coronary artery disease patients and controls a prolonged increase in low frequency/high frequency ratio was observed after the first sauna exposure. CONCLUSIONS: Acute exposure to Finnish sauna and cold-water immersion causes haemodynamic alterations in chronic heart failure patients similarly to control subjects and in particular did not provoke an excessive increase in adrenergic activity or complex arrhythmias. PMID- 26152774 TI - Prenatal and maternal characteristics and later risk for coronary heart disease among women. AB - OBJECTIVE: The pace and pathways of early growth have major influences on later health. Coronary heart disease (CHD) is a major killer and kills more women than men, but usually manifests about 10 years later in women. Therefore there are fewer studies of early growth and CHD amongst women than men. METHODS: The Helsinki Birth Cohort Study includes 9817 women born during 1924-1944. We used national registers to identify hospital admissions and deaths from CHD during 1971-2010. We used a Cox model to obtain hazard ratios (HRs) for CHD. RESULTS: Altogether 967 women (9.9%) developed CHD. Socioeconomic factors were strongly and inversely associated with CHD. Neither maternal age nor body mass index (BMI) was associated with CHD in the daughters. There were inverse associations of birth weight (p = 0.07) and length (p = 0.02) with CHD in adult life. We divided the mothers according to parity. Daughters of primiparous women had lower birth weight and shorter birth length than the offspring of multiparous women (both p values < 0.001). Birth weight (p = 0.008), birth length (p = 0.05) and birth BMI (p = 0.02) were all inversely associated with CHD. Among first-born women, a 1 kg increase in birth weight was associated with a 25% lower risk for CHD (HR 0.75, 95% confidence interval (CI) 0.60-0.93). The findings changed little after adjustment for socioeconomic factors. Among later-born women none of the birth characteristics was associated with CHD. CONCLUSIONS: Small birth size is associated with CHD among women. First-born women with high birth weight appear to be at lower risk for CHD compared with later born women. PMID- 26152775 TI - Circulating tocopherols and risk of coronary artery disease: A systematic review and meta-analysis. AB - BACKGROUND: Circulating level of tocopherols was supposed to be associated with risk of coronary artery disease. However, the results from previous studies remain controversial. Therefore, we conducted a meta-analysis based on observational studies to evaluate the association between circulating tocopherols and coronary artery disease risk for the first time. DESIGN: Meta-analysis. METHODS: PubMed, Embase and Cochrane databases were searched to retrieve articles published during January 1995 and May 2015. Articles were included if they provided sufficient information to calculate the weighted mean difference and its corresponding 95% confidence interval. RESULTS: Circulating level of total tocopherols was significantly lower in coronary artery disease patients than that in controls (weighted mean difference -4.33 MUmol/l, 95% confidence interval 6.74 to -1.91, P < 0.01). However, circulating alpha-tocopherol alone was not significantly associated with coronary artery disease risk. Results from subgroup analyses showed that a lower level of circulating total tocopherols was merely associated with higher coronary artery disease risk in studies with higher sex ratio in cases (<2, weighted mean difference -0.07 MUmol/l, 95% confidence interval -1.15 to 1.00, P = 0.90; >= 2, weighted mean difference -6.00 MUmol/l, 95% confidence interval -9.76 to -2.22, P < 0.01). Similarly, a lower level of circulating total tocopherols was associated with early onset coronary artery disease rather than late onset coronary artery disease (<60 years, weighted mean difference -5.40 MUmol/l, 95% confidence interval -9.22 to -1.57, P < 0.01; >= 60 years, weighted mean difference -1.37 MUmol/l, 95% confidence interval -3.48 to 0.74, P = 0.20). We also found some discrepancies in circulating total tocopherols when the studies were stratified by matching status and assay methods. CONCLUSIONS: Our findings suggest that a deficiency in circulating total tocopherols might be associated with higher coronary artery disease risk. Whereas circulating alpha-tocopherol alone could not protect us from developing coronary artery disease. Further prospective studies were warranted to confirm our findings. PMID- 26152776 TI - 'I didn't even know boys could get the vaccine': Parents' reasons for human papillomavirus (HPV) vaccination decision making for their sons. AB - OBJECTIVE: The study's objective was to examine parents' reasons for their decision to vaccinate their 9-16-year-old sons with the human papillomavirus (HPV) vaccine. METHODS: Using the precaution adoption process model (PAPM), parents were classified according to one of six stages of decision making: unaware, unengaged, undecided, decided not to vaccinate, decided to vaccinate, or vaccinated. Parents responded to an open-ended question: 'What would influence your decision to have your son vaccinated or not against HPV?' RESULTS: Three thousand one hundred and seventeen parents provided 2,874 interpretable narrative responses that were coded using thematic content analyses. The majority of parents were in the earlier precaution adoption process model stages, that is, unaware that the HPV vaccine could be given to boys (57.0%), unengaged (20.9%), or undecided (9.1%). Needing more information, vaccine cost, risks associated with vaccination, and wanting a doctor's recommendation influenced these earlier staged parents' decisions. Parents who decided not to vaccinate their sons (6.8%) reported their decision was due to the risks, insufficient research, lack of confidence in vaccines, and/or no need for the vaccine (as their sons are not sexually active and/or too young). Parents who had decided to vaccinate their sons (5.0%) or who had vaccinated their sons (1.1%) reported that their decisions were based on protecting their sons' health and preventing disease. CONCLUSION: There are important differences in the factors that influence parents' decision depending on where they are along the decision-making trajectory. Assuring that parents are well informed about the importance of male vaccination, reducing vaccine cost, accurately communicating vaccine safety, and improving patient provider communication may augment vaccine coverage and prevent HPV-associated cancers in Canada. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26152777 TI - The effect of short fasting on the hypothalamic neuronal system of kisspeptin in peripubertal female lambs. AB - Changes in the metabolic state induced by feed restrictions have a negative effect on the reproduction in mammals and result in the delayed puberty onset. Kisspeptin (kp) has been demonstrated as a pivotal regulator of GnRH/LH secretion during puberty. To elucidate the involvement of kp in the hypothalamic secretory function in altered metabolic state, the expression of kp protein was investigated in peripubertal female lambs after short fasting. The experiment was conducted on immature 32-weeks old Merino lambs fed standard diet (n=5) or fasted for 72h (n=5). The localization and expression of kp was evaluated using immunohistochemistry. Serum LH concentration was determined using radioimmunology. In the hypothalami of fasted sheep, the number of kp perikarya and the percent of density of neuronal kp network in the caudal part of the nucleus arcuatus were significantly less (P<0.001) than in standard fed lambs. The decrease of kp axons throughout areas extending from area preoptica to medial basal hypothalamus and in the median eminence in fasted lambs compared to standard fed ones was observed. Plasma LH concentrations and amplitude of pulses decreased (P<0.05) after 3 days of fasting compared to standard fed group. The decrease of the kp expression is likely due to diminished kp protein synthesis, and its storage in the neurons. In summary, the data are the first to demonstrate interactions between metabolic status and kp neuronal system in lambs before puberty, and suggest that kp neurons may represent a link between metabolic signals and central control of reproduction. PMID- 26152778 TI - Interferon-alpha curbs production of interleukin-22 by human peripheral blood mononuclear cells exposed to live Borrelia burgdorferi. AB - Cytokine networks initiated by means of innate immunity are regarded as a major determinant of host defence in response to acute infection by bacteria including Borrelia burgdorferi. Herein, we demonstrate that interferon (IFN)-alpha, either endogenously produced after exposure of cells to toll-like receptor-9-activating CpG oligonucleotides or provided as recombinant cytokine, weakens activation of the anti-bacterial interleukin (IL)-1/IL-22 axis in human peripheral blood mononuclear cells exposed to viable B. burgdorferi. As IFN-alpha has been related to pathological dissemination of the spirochaete, data suggest an immunoregulatory role of type I IFN in this context that is able to significantly modify cytokine profiles thereby possibly determining early course of B. burgdorferi infection. PMID- 26152779 TI - High Rates of Interest in Sex in Patients With Hip Arthritis. AB - BACKGROUND: Being sexually active has been associated with a high quality of life. Unfortunately, the topic of sexual limitations in patients undergoing total hip arthroplasty (THA) has not been well studied. QUESTION/PURPOSES: (1) What proportion of patients experience sexual limitations because of hip arthritis before THA; (2) whether patient reports of sexual limitations would be associated with poorer results on general health and hip-specific instruments; and (3) whether patient reports of sexual limitations would be associated with poorer preoperative range of motion. METHODS: Between May 19, 2003, and August 17, 2009, 403 patients (423 hips) underwent primary THA; of those, 237 patients/hips (59% [237 of 403]) had addressed the new patient questionnaire within 1 year before surgery and had it available for review; and of those, 192 (48% [192 of 403]) had answered the question about sexual function on their questionnaire. This group included 159 patients who were sexually active (82% [159 of 192]). These patients were defined as our study cohort. Among them, 131 patients (82% [131 of 159]) reported some degree of sexual limitations and 28 patients (18% [28 of 159]) did not report limitations. Patient characteristics evaluated included baseline demographics, body mass index, American Society of Anesthesiologists, Charlson in addition to preoperative/postoperative pain intensity/frequency (visual analog scale, 0-10), SF-36, WOMAC, and baseline hip range of motion measures. Outcomes of interest were compared between both groups. Mean age was 65 years. Chi-square, t-tests, and multivariate analysis of variance were used. Alpha was set at 0.05. RESULTS: Hip arthritis interfered with the sexual life of 82% (131 of 159) of sexually active patients, more so in women than men (96% [68 of 71], versus 72% [63 of 88]; odds ratio, 8.99; 95% confidence interval, 2.588-31.258; p = 0.001). Preoperatively, patients with sexual limitations had a mean pain intensity of 8 +/- 1.84 points on the visual analog scale, whereas patients without limitations had 6 +/- 1.99 points (p < 0.001). Differences were also found in WOMAC pain (11 +/- 3.9 versus 8 +/- 3.5; p = 0.004) and WOMAC stiffness (3.4 +/- 2.3 versus 1.4 +/- 1.7; p = 0.001). Baseline hip flexion (84 degrees +/- 22.4 degrees versus 93 degrees +/- 16.5 degrees , respectively; p = 0.04) and external rotation (23 degrees +/- 14.5 degrees versus 30 degrees +/- 11.6 degrees ; p = 0.02) were also different. CONCLUSIONS: Our data suggest that many patients getting a hip arthroplasty are sexually active but most patients who are sexually active have sexual limitations before surgery as a result of hip arthritis. Women are more affected than men. Patients with these limitations experience more pain and have less flexion and external rotation before surgery. Preoperatively, counseling on sexual activities should be routinely discussed with all patients undergoing THA. LEVEL OF EVIDENCE: Level III, prognostic study. PMID- 26152780 TI - CORR Insights((r)): Surface Damage Is Not Reduced With Highly Crosslinked Polyethylene Tibial Inserts at Short-term. PMID- 26152781 TI - Catastrophic Femoral Neck Failure after THA with the Accolade((r)) I Stem in Three Patients. AB - CASE DESCRIPTION: We report a series of three femoral stem failures, each occurring at the head-neck junction, with all patients experiencing limited and painful ambulation, leading to subsequent revision arthroplasty. All patients were male with high-offset femoral stems and increased head lengths, and each had undergone primary THA at a minimum of 7 years before presentation (average, 94 months). There were no associated deep infections or cases of aseptic loosening in the cohort. LITERATURE REVIEW: There is a paucity of similar reports in the literature regarding femoral stem failure at the head-neck junction. When failures of titanium stems have been reported, failure has been attributed to material design and geometry, laser etching, overload, implant alignment, and patient characteristics. PURPOSE AND CLINICAL RELEVANCE: Catastrophic failures of femoral stems at the head-neck junction are a rare cause for revision after THA. Component material and design, surgical technique, and patient factors may contribute. PMID- 26152782 TI - Elbow Positioning and Joint Insufflation Substantially Influence Median and Radial Nerve Locations. AB - BACKGROUND: The median and radial nerves are at risk of iatrogenic injury when performing arthroscopic arthrolysis with anterior capsulectomy. Although prior anatomic studies have identified the position of these nerves, little is known about how elbow positioning and joint insufflation might influence nerve locations. QUESTIONS/PURPOSES: In a cadaver model, we sought to determine whether (1) the locations of the median and radial nerves change with variation of elbow positioning; and whether (2) flexion and joint insufflation increase the distance of the median and radial nerves to osseous landmarks after correcting for differences in size of the cadaveric specimens. METHODS: The median and radial nerves were marked with a radiopaque thread in 11 fresh-frozen elbow specimens. Three-dimensional radiographic scans were performed in extension, in 90 degrees flexion, and after joint insufflations in neutral rotation, pronation, and supination. Trochlear and capitellar widths were analyzed. The distances of the median nerve to the medial and anterior edge of the trochlea and to the coronoid were measured. The distances of the radial nerve to the lateral and anterior edge of the capitulum and to the anterior edge of the radial head were measured. We analyzed the mediolateral nerve locations as a percentage function of the trochlear and capitellar widths to control for differences regarding the size of the specimens. RESULTS: The mean distance of the radial nerve to the lateral edge of the capitulum as a percentage function of the capitellar width increased from 68% +/- 17% in extension to 91% +/- 23% in flexion (mean difference = 23%; 95% confidence interval [CI], 5%-41%; p = 0.01). With the numbers available, no such difference was observed regarding the location of the median nerve in relation to the medial border of the trochlea (mean difference = 5%; 95% CI, -13% to 22%; p = 0.309). Flexion and joint insufflation increased the distance of the nerves to osseous landmarks. The mean distance of the median nerve to the coronoid tip was 5.4 +/- 1.3 mm in extension, 9.1 +/- 2.3 mm in flexion (mean difference = 3.7 mm; 95% CI, 2.04-5.36 mm; p < 0.001), and 12.6 +/- 3.6 mm in flexion and insufflation (mean difference = 3.5 mm; 95% CI, 0.81-6.19 mm; p = 0.008). The mean distance of the radial nerve to the anterior edge of the radial head increased from 4.7 +/- 1.8 mm in extension to 7.7 +/- 2.7 mm in flexion (mean difference = 3.0 mm; 95% CI, 0.96-5.04 mm; p = 0.005) and to 11.9 +/- 3.0 mm in flexion with additional joint insufflation (mean difference = 4.2 mm; 95% CI, 1.66-6.74 mm; p = 0.002). CONCLUSIONS: The radial nerve shifts medially during flexion from the lateral to the medial border of the inner third of the capitulum. The median nerve is located at the medial quarter of the joint. The distance of the median and radial nerves to osseous landmarks doubles from extension to 90 degrees flexion and triples after joint insufflation. CLINICAL RELEVANCE: Elbow arthroscopy with anterior capsulectomy should be performed cautiously at the medial aspect of the joint to avoid median nerve lesions. Performing arthroscopic anterior capsulectomy in flexion at the lateral aspect of the joint and in slight extension at the medial edge of the capitulum could enhance safety of this procedure. PMID- 26152783 TI - Does Microwave Ablation of the Tumor Edge Allow for Joint-sparing Surgery in Patients With Osteosarcoma of the Proximal Tibia? AB - BACKGROUND: Joint-sparing surgery of a patient's native joint for osteosarcoma likely affords better function and comparable survival. However, it sometimes is challenging to resect a juxtaarticular osteosarcoma in a way that preserves the affected epiphysis because wide margins are necessary to minimize the risk of local recurrence. If there was a method to resect a tumor close to the joint and treat a potentially positive margin to prevent recurrence, it might allow salvage of a joint that otherwise might be lost. QUESTIONS/PURPOSES: We therefore asked (1) whether joint-preserving tumor resection could be performed for juxtaarticular osteosarcoma after microwave ablation of the tumor edge under navigation without leading to local recurrences, (2) what is the resulting function, and (3) what are the complications associated with this procedure. METHODS: Between 2009 and 2011, we treated 11 patients who had juxtaarticular osteosarcoma of the proximal tibia (mean age, 12 years; range, 9-16 years) with joint-preserving surgery by transepiphysis tumor resection after navigation assisted microwave ablation of the tumor edge; they were followed a minimum of 37 months (mean, 48 months; range 37-62 months), and none was lost to followup. Patients were considered eligible for this procedure if they had a distance from the tumor edge to the articular surface between 10 to 15 mm, good chemotherapy responses, no pathologic fracture and no tumor involvement of major neurovascular structures. Allograft in combination with a vascularized fibula flap was used for segmental reconstruction. We recorded local tumor control, complications, and functional outcomes using the Musculoskeletal Tumor Society score, which ranges from 0 to 30, with higher scores indicating better function. RESULTS: There were no local recurrences. Major complications included osteonecrosis of part of the epiphysis in two patients and deep infection in one. The Musculoskeletal Tumor Society score ranged from 26 to 30 with a mean of 29. CONCLUSIONS: In selected patients with osteosarcoma invading the epiphysis, navigated resection facilitates performing joint-sparing surgery, and in our small series, the adjuvant microwave ablation seemed to provide adequate local tumor control. Although more experience and longer followup are needed, this approach may make it possible to salvage more native joints when performing limb salvage for osteosarcoma. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 26152784 TI - CORR Insights((r)): does native combined anteversion influence pain onset in patients with dysplastic hips? PMID- 26152785 TI - Supramolecular Assemblies Responsive to Biomolecules toward Biological Applications. AB - Stimuli-responsive supramolecular assemblies consisting of small molecules are attractive functional materials for biological applications such as drug delivery, medical diagnosis, enzyme immobilization, and tissue engineering. By use of their dynamic and reversible properties, many supramolecular assemblies responsive to a variety of biomolecules have been designed and synthesized. This review focuses on promising strategies for the construction of such dynamic supramolecular assemblies and their functions. While studies of biomolecule responsive supramolecular assemblies have mainly been performed in vitro, it has recently been demonstrated that some of them can work in live cells. Supramolecular assemblies now open up new avenues in chemical biology and biofunctional materials. PMID- 26152786 TI - Interaction between lamellar twinning and catalyst dynamics in spontaneous core shell InGaP nanowires. AB - Semiconductor nanowires oriented along the [211] direction usually present twins parallel to their axis. For group IV nanowires this kind of twin allows the formation of a catalyst-nanowire interface composed of two equivalent {111} facets. For III-V nanowires, however, the twin will generate two facets with different polarities. In order to keep the <211> orientation stable, a balance in growth rates for these different facets must be reached. We report here the observation of stable, micron-long <211>-oriented InGaP nanowires with a spontaneous core-shell structure. We show that stacking fault formation in the crystal region corresponding to the {111}A facet termination provides a stable NW/NP interface for growth along the <211> direction. During sample cool down, however, the catalyst migrates to a lateral {111}B facet, allowing the growth of branches perpendicular to the initial orientation. In addition to that, we show that the core-shell structure is non-concentric, most likely due to the asymmetry between the facets formed in the NW sidewall; this effect generates stress along the nanowire, which can be relieved through bending. PMID- 26152788 TI - Sex differences and blood pressure regulation in humans. AB - NEW FINDINGS: What is the topic of this review? Over the past decade, our team has investigated interindividual variability in human blood pressure regulation. What advances does it highlight? In men, we have found a tight relationship between indices of sympathetic activity and vascular resistance across the age span. This relationship is absent in young women but seen in postmenopausal women. These sex and age differences in vascular resistance are largely a result of changes in the balance of vasodilating and vasoconstricting adrenergic receptor tone. When these changes are considered along with cardiac output, a coherent picture is beginning to emerge of why blood pressure rises more with age in women than men. Arterial pressure is a key regulated variable in the cardiovascular system with important health implications. Over the last 12 years, we have used physiological measurements, including muscle sympathetic nerve activity (MSNA), to explore the balance among mean arterial blood pressure, cardiac output and total peripheral resistance (TPR) in normotensive humans. We have shown that these determinants of blood pressure can vary widely in different subjects and how they vary depends on sex and age. In young men, there is a direct relationship between MSNA and TPR but no relationship with blood pressure. This is because cardiac output is proportionally lower in those with high MSNA and TPR. In contrast, in young women there is no relationship between MSNA and TPR (or cardiac output); this is because beta-adrenergic vasodilator mechanisms offset alpha-adrenergic vasoconstriction. Thus, blood pressure is unrelated to MSNA in young women. In older women, beta-adrenergic vasodilator mechanisms are diminished, and a direct relationship between MSNA and TPR is seen. In older men, the relationships among these variables are less clear cut, perhaps owing to age related alterations in endothelial function. With ageing, the relationship between MSNA and blood pressure becomes positive, more so in women than in men. The finding that the physiological control of blood pressure is so different in men and women and that it varies with age suggests that future studies of mechanisms of hypertension will reveal corresponding differences among groups. PMID- 26152789 TI - Enhancing the efficiency of sortase-mediated ligations through nickel-peptide complex formation. AB - A modified sortase A recognition motif containing a masked Ni(2+)-binding peptide was employed to boost the efficiency of sortase-catalyzed ligation reactions. Deactivation of the Ni(2+)-binding peptide using a Ni(2+) additive improved reaction performance at low to equimolar ratios of the glycine amine nucleophile and sortase substrate. The success of this approach was demonstrated with both peptide and protein substrates. PMID- 26152787 TI - A NOTCH1 gene copy number gain is a prognostic indicator of worse survival and a predictive biomarker to a Notch1 targeting antibody in colorectal cancer. AB - Dysregulation of the Notch1 receptor has been shown to facilitate the development and progression of colorectal cancer (CRC) and has been identified as an independent predictor of disease progression and worse survival. Although mutations in the NOTCH1 receptor have not been described in CRC, we have previously discovered a NOTCH1 gene copy number gain in a portion of CRC tumor samples. Here, we demonstrated that a NOTCH1 gene copy number gain is significantly associated with worse survival and a high percentage of gene duplication in a cohort of patients with advanced CRC. In our CRC patient-derived tumor xenograft (PDTX) model, tumors harboring a NOTCH1 gain exhibited significant elevation of the Notch1 receptor, JAG1 ligand and cleaved Notch1 activity. In addition, a significant association was identified between a gain in NOTCH1 gene copy number and sensitivity to a Notch1-targeting antibody. These findings suggest that patients with metastatic CRC that harbor a gain in NOTCH1 gene copy number have worse survival and that targeting this patient population with a Notch1 antibody may yield improved outcomes. PMID- 26152790 TI - Early post mortem expression of genes related to tenderization in two Italian Simmental young bulls' skeletal muscles differing in contractile type. AB - The early post mortem expression of eight genes potentially involved in meat ageing process and the tenderness of two Italian Simmental young bulls' (Bos taurus) skeletal muscles differing in their contractile type were evaluated. Samples of Longissimus lumborum (LL) and Infraspinatus (IS) muscles were collected from 17 bulls. The messenger RNA (mRNA) abundances of calpain-1, calpain-2, calpastatin, caspase 3, caspase 9, heat shock protein 27 (Hsp27), Hsp40 and Hsp70 were detected by quantitative PCR. The myosin heavy chain-slow and -fast isoform content, the pH48h and the lipid content of the muscles were in line with the contractile and metabolic type. In comparison with the fast LL, the slow IS showed a lower calpain-1/calpastatin mRNA content ratio after slaughtering and a higher Warner-Bratzler Initial Yield value after 7 days of ageing. Hsp27 and Hsp70 mRNA abundances were significantly lower in LL than IS, highlighting their potential role in the ageing process of bovine muscles. PMID- 26152791 TI - Economic impact of homeopathic practice in general medicine in France. AB - Health authorities are constantly searching for new ways to stabilise health expenditures. To explore this issue, we compared the costs generated by different types of medical practice in French general medicine: i.e. conventional (CM-GP), homeopathic (Ho-GP), or mixed (Mx-GP).Data from a previous cross-sectional study, EPI3 La-Ser, were used. Three types of cost were analysed: (i) consultation cost (ii) prescription cost and (iii) total cost (consultation + prescription). Each was evaluated as: (i) the cost to Social Security (ii) the remaining cost (to the patient and/or supplementary health insurance); and (iii) health expenditure (combination of the two costs).With regard to Social Security, treatment by Ho GPs was less costly (42.00 vs 65.25 for CM-GPs, 35 % less). Medical prescriptions were two-times more expensive for CM-GPs patients (48.68 vs 25.62 ). For the supplementary health insurance and/or patient out-of pocket costs, treatment by CM-GPs was less expensive due to the lower consultation costs (6.19 vs 11.20 for Ho-GPs) whereas the prescription cost was comparable between the Ho-GPs and the CM-GPs patients (15.87 vs 15.24 respectively) . The health expenditure cost was 20 % less for patients consulting Ho-GPs compared to CM-GPs (68.93 vs 86.63 , respectively). The lower cost of medical prescriptions for Ho-GPs patients compared to CM-GPs patients (41.67 vs 63.72 ) was offset by the higher consultation costs (27.08 vs 22.68 respectively). Ho-GPs prescribed fewer psychotropic drugs, antibiotics and non-steroidal anti inflammatory drugs.In conclusions management of patients by homeopathic GPs may be less expensive from a global perspective and may represent an important interest to public health. PMID- 26152792 TI - Identification of Toxoplasma gondii protein fractions induce immune response against melanoma in mice. AB - Dendritic cells (DCs) play a crucial role in the initiation of adaptive immune responses against tumor cells. We recently found that protein components of Toxoplasma gondii (T. gondii) could mature DCs efficiently. Therefore, in this study, we aimed to find the most effective protein components of T. gondii which are able to mature DCs and consequently instruct immune responses in tumor bearing mice. Soluble tachyzoite antigens (STAgs) were fractionated by ammonium sulfate precipitation and subsequently by anion-exchange HPLC. Immature DCs (iDCs) were treated by these protein fractions and were monitored for IL-12p70 and IL-10 production. Moreover, the capacity of mature DCs (mDCs) to induce lymphocyte proliferation was investigated. Ultimately, we analyzed the ability of mDCs in instructing immune responses in tumor-bearing mice. We found that ammonium sulfate fraction one (A1) matured-DCs produced higher IL-12 level and IL 12/IL-10 ratio; therefore, this fraction was selected for further fractionation by anion-exchange HPLC. The results showed that anion-exchange HPLC fraction 14 (C14) matured-DCs secrete higher levels of IL-12p70 and IL-12p70/IL-10 ratio. Survival of the mice matured by A1 fraction increased significantly compared to other groups. Moreover, SDS-PAGE electrophoresis showed that different obtained fractions have distinct proteins based on their size. These results demonstrate that two protein fractions of T. gondii are able to mature DCs more efficient. PMID- 26152793 TI - Cyanidin-3-O-glucoside attenuates acute lung injury in sepsis rats. AB - BACKGROUND: Sepsis is a complex syndrome with high mortality, which often induces acute lung injury (ALI) and acute respiratory distress syndrome. Cyanidin-3-O glucoside (C3G), the most active anthocyanin in the blueberry extracts, has been demonstrated to have pulmonary protective effects in some ALI models. This study aims to evaluate the potential protective effect of C3G on sepsis-evoked ALI in rats. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) was performed on Sprague-Dawley rats to establish sepsis-induced ALI model. Rats were injected intraperitoneally with 10 or 30 mg/kg of C3G after CLP and then the survival was recorded every 12 h for 96 h. The pulmonary protective effects of C3G on CLP induced ALI were evaluated at 24 h after CLP. RESULTS: The results demonstrated that C3G treatment significantly improved the survival rate of CLP rats and attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, protein leak, infiltration of leukocytes, and myeloperoxidase activity. In addition, C3G markedly decreased malondialdehyde content and increased superoxide dismutase activity and glutathione level. Serum levels of tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 were also decreased by C3G administration, as well as protein expression of cyclooxygenase-2 and production of prostaglandin E2 in the lung. Furthermore, C3G treatment upregulated protein expression of inhibitors of NF-kappaBalpha and downregulated expressions of nuclear factor kappa-B (NF-kappaB) p65 and p-p65 in the lung, thereby inhibiting the NF-kappaB-DNA binding activity. CONCLUSIONS: These findings indicate that C3G exerts pulmonary protective effects on CLP-induced ALI rats. The effect may be associated with NF-kappaB signaling pathway suppression. PMID- 26152794 TI - The association of autoimmune diseases with pediatric ulcerative colitis does not influence its disease course. AB - OBJECTIVE: Ulcerative colitis (UC) is a chronic inflammatory condition. Previous reports suggested that UC may have a worse prognosis when associated with auto immune diseases. We compared characteristics at diagnosis and natural history of the disease between classical ulcerative colitis (CUC) and UC associated with auto-immune diseases (CAI) in children. MATERIAL AND METHODS: In this study, 67 children followed for UC at Nancy University Hospital between 1993 and 2012 were included: 45 patients in the CUC group and 22 in the CAI group. RESULTS: Median follow-up was 4.8 years. Median age at diagnosis was 11.6 years in the CAI group and 9.8 years in the CUC group. Time between symptoms onset and diagnosis was broadly similar in the two groups (<3 months) and there were no significant differences regarding biological and histological findings. At 5 years, the need for corticosteroids and azathioprine did not differ between the CAI and the CUC groups. There was also no significant difference between the two groups regarding infliximab use at 1 and 5 years. CONCLUSIONS: In this pediatric study, CAI had similar characteristics at baseline as CUC. The course of CAI does not seem to be influenced by the presence of concomitant auto-immune diseases. PMID- 26152795 TI - Host behaviour drives parasite genetics at multiple geographic scales: population genetics of the chewing louse, Thomomydoecus minor. AB - Pocket gophers and their symbiotic chewing lice form a host-parasite assemblage known for a high degree of cophylogeny, thought to be driven by life history parameters of both host and parasite that make host switching difficult. However, little work to date has focused on determining whether these life histories actually impact louse populations at the very fine scale of louse infrapopulations (individuals on a single host) at the same or at nearby host localities. We used microsatellite and mtDNA sequence data to make comparisons of chewing-louse (Thomomydoecus minor) population subdivision over time and over geographic space where there are different potential amounts of host interaction surrounding a zone of contact between two hybridizing pocket-gopher subspecies. We found that chewing lice had high levels of population isolation consistent with a paucity of horizontal transmission even at the very fine geographic scale of a single alfalfa field. We also found marked genetic discontinuity in louse populations corresponding with host subspecies and little, if any, admixture in the louse genetic groups even though the lice are closely related. The correlation of louse infrapopulation differentiation with host interaction at multiple scales, including across a discontinuity in pocket-gopher habitat, suggests that host behaviour is the primary driver of parasite genetics. This observation makes sense in light of the life histories of both chewing lice and pocket gophers and provides a powerful explanation for the well-documented pattern of parallel cladogenesis in pocket gophers and chewing lice. PMID- 26152797 TI - First living-related liver transplant to cure factor VII deficiency. AB - Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first-ever youngest baby reported worldwide. A six-month-old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life-threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre-, intra- and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency. PMID- 26152796 TI - TGFbeta1 secreted by cancer-associated fibroblasts induces epithelial-mesenchymal transition of bladder cancer cells through lncRNA-ZEB2NAT. AB - Urinary bladder cancer (UBC) patients at muscle invasive stage have poor clinical outcome, due to high propensity for metastasis. Cancer-associated fibroblasts (CAFs), one of the principal constituents of the tumor stroma, play an important role in tumor development. However, it is unclear whether CAFs from UBC induce cell invasion and which signaling pathway is involved. Herein, we found that conditional medium from UBC CAFs (CAF-CM) enhanced the invasion of UBC cells. CAF CM induced the epithelial-mesenchymal transition (EMT) by regulating expression levels of EMT-associated markers in UBC cells. Higher concentration of TGFbeta1 in CAF-CM, comparing with the CM from adjacent normal fibroblast, led to phosphorylation of Smad2 in UBC cells. Additionally, inhibition of TGFbeta1 signaling decreased the EMT-associated gene expression, and cancer cell invasion. Interestingly, a long non-coding RNA, ZEB2NAT, was demonstrated to be essential for this TGFbeta1-dependent process. ZEB2NAT depletion reversed CAF-CM-induced EMT and invasion of cancer cells, as well as reduced the ZEB2 protein level. Consistently, TGFbeta1 mRNA expression is positively correlated with ZEB2NAT transcript and ZEB2 protein levels in human bladder cancer specimens. Our data revealed a novel mechanism that CAFs induces EMT and invasion of human UBC cells through the TGFbeta1-ZEB2NAT-ZEB2 axis. PMID- 26152798 TI - Critical MRI markers in transient ischemic attack. PMID- 26152799 TI - Mediterranean spotted fever: an unusual clinical and neuroradiological presentation. PMID- 26152800 TI - The contribution of GIGYF2 to Parkinson's disease: a meta-analysis. AB - The contribution of the gene of GIGYF2, Grb10-Interacting GYF Protein 2, to Parkinson's disease (PD) is still ambiguous. To explore the contribution of GIGYF2 to PD at the genetic level, we analyzed the relationship between all reported GIGYF2 variants (including mutations and polymorphisms) and PD through a meta-analysis. Databases including Medline, Embase, etc., were searched to find relevant studies. All eligible publications have to meet the strict inclusion and exclusion criteria listed. Two authors independently selected trials, assessed the article's quality and extracted data. Odds ratios (ORs) and relative risks with 95 % confidence intervals (CIs) were used to evaluate the strength of associations. All analyses were carried out by using the Review Manager software package v.5.2. More than 100 variants of GIGYF2 were reported either or both in patients and controls in 10 included publications. The 10 publications totally included 5466 patients and 6517 controls. We conducted meta-analyses for the following variants: N56S, N457T, Del LPQQQQQQ 1209-1216, Del Q 1210 (rs10555297), rs12328151, rs2289912, rs2305138, rs3816334, A572A and H1171R. The ORs for N56S were 2.86 (95 % CI 1.10, 7.41) for PD and 4.75 (95 % CI 1.35, 16.68) for FPD. And the OR for N457T in FPD was 4.53 (95 % CI 1.04, 19.66). On the other hand, other variants involved in meta-analyses were not related to PD. This research results suggest that the N56S and N457T of GIGYF2 are risk factors for PD in Caucasians, but not in Asians. PMID- 26152801 TI - The association between clinically relevant anxiety and other non-motor symptoms in Parkinson's disease. AB - Anxiety disorders in patients with Parkinson's disease (PD) are often missed due to an overlap with other non-motor symptoms. The relationships between anxiety and other non-motor symptoms in PD still remain unclear. We used the Hamilton anxiety rating scale and the Non-motor Symptoms Questionnaire to measure anxiety and the complex range of non-motor symptoms in 99 PD patients. The relationships between anxiety and other PD-related non-motor symptoms were examined through regression analyses. 25 % of PD patients were diagnosed with clinically relevant anxiety. Non-motor symptoms were more prominent in patients with anxiety. Depression, urinary disorders, and sleep disruption were the factors most likely to influence anxiety in PD. Our findings have revealed a strong interplay between anxiety and other non-motor symptoms of PD and have highlighted the need for a holistic approach towards the clinical treatment of this disabling condition. PMID- 26152802 TI - Long-term survival in a patient with muscle-eye-brain disease. PMID- 26152803 TI - The role of routine hearing screening in children with cystic fibrosis on aminoglycosides: A systematic review. AB - OBJECTIVE: To review the role of routine hearing screening for sensorineural hearing loss (SNHL) in children with cystic fibrosis (CF) who have been on aminoglycoside therapy. DATA SOURCES: PubMed, Cochrane, Scopus, and Ovid databases. REVIEW METHODS: A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines. A comprehensive search was performed from 1970 to 2014. Randomized controlled trials, case-control studies, cohort studies, and case series including pediatric subjects with baseline auditory evaluations were included. RESULTS: Twelve studies (1979-2014) were reviewed. The study population included 762 children (5 months-20 years). Hearing screening measures included pure-tone audiometry (PTA) at standard +/- high frequency threshold (HFPTA) (12/12), distortion product otoacoustic emissions (DPOAE) (4/12), transient evoked otoacoustic emissions (1/12), and automated auditory brainstem response (1/12). The overall prevalence of SNHL ranged from 0% to 29%. However, on subset analysis of children with greater than 10 courses of intravenous (IV) aminoglycosides, up to 44% had SNHL. Eight studies recommended hearing screening in CF children on aminoglycosides; of these, two studies recommended screening even without aminoglycoside exposure, and four studies made no recommendations. HFPTA was the most commonly recommended screening measure followed by DPOAEs. CONCLUSION: This systematic review supports a recommendation for clinicians to perform routine hearing screening in children with CF during and after aminoglycoside exposure based on the high prevalence of SNHL in this population. Future studies should define the optimal timing for hearing screening during and after aminoglycoside therapy in children with CF. PMID- 26152805 TI - The Space That Difference Makes: On Marginality, Social Justice and the Future of the Health Humanities. AB - Feminist theorist and educator, bell hooks, asserts that to seek true liberation one must choose marginality. One must choose to occupy the space outside the binary between colonizer-colonized, hegemonic center-periphery, and us-them in order to create a location of possibility. This essay will reveal the practice of social justice as the navigation of the space that difference makes and argue that choosing marginality provides a framework for health humanities work towards social justice in health care. The space of the launderette that is depicted in Hanif Kureishi's 1986 film, My Beautiful Laundrette, provides an example of choosing marginality and illustrates how difference structures both real and imagined spaces, which influences how individuals ultimately perceive one another. We will draw from the work of bell hooks; political geographer, Edward Soja; and Marxist philosopher, Henri Lefebvre, to demonstrate the importance of the health humanities' position at the margin to traditional health care education. PMID- 26152804 TI - ALK and ROS1 rearrangements tested by fluorescence in situ hybridization in cytological smears from advanced non-small cell lung cancer patients. AB - BACKGROUND: The identification of ALK and ROS1 rearrangements and the availability of an effective target therapy, such as crizotinib, represent a new option in the treatment of advanced non-small cell lung cancer (NSCLC) patients. In light of recent advances in non-invasive diagnostic procedures, we aimed to demonstrate that direct cytological smears are suitable for assessing ALK and ROS1 rearrangements in patients with NSCLC. METHODS: Fifty-five patients with a cytological diagnosis of lung adenocarcinoma (ADC) were evaluated for ALK rearrangements by fluorescence in situ hybridization (FISH) and 12 patients for ROS1 FISH rearrangements. Seventeen of the 55 cytological samples tested for ALK were obtained from the primary tumor and 38 from metastatic lesions. Ten of 12 samples evaluated for ROS1 were obtained from metastatic sites and two from the primary tumor. RESULTS: ALK FISH was successful in 49/55 (89%) cytological ADC samples and ROS1 FISH in all 12 cytological samples. ALK rearrangements were found in 3/13 (23%) primary tumors and 7/36 (19%) metastatic sites. ROS1 rearrangements were found in one of the two primary tumors and in two of the 10 metastases. Two of the three rearranged cases were tested on cytology after knowing that they were rearranged on histology in order to increase representativeness of ROS1 rearranged cases in this study. CONCLUSION: Whenever cytology represents the only available material for diagnosis and biological characterization of NSCLC, minimally invasive procedures may provide an additional important source of cellular material for FISH assessment of ALK and ROS1 rearrangements. PMID- 26152806 TI - Sedation after airway reconstruction in children: A protocol to reduce withdrawal and length of stay. PMID- 26152808 TI - Neuroimaging-Aided Prediction of the Effect of Methylphenidate in Children with Attention-Deficit Hyperactivity Disorder: A Randomized Controlled Trial. PMID- 26152807 TI - Neighbor-directed histidine N (tau)-alkylation: A route to imidazolium-containing phosphopeptide macrocycles. AB - Our recently discovered, selective, on-resin route to N(tau)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring forming junctions. Interestingly, these cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Neighbor directed histidine N(tau)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts. PMID- 26152809 TI - Parity-dependent State Engineering and Tomography in the ultrastrong coupling regime. AB - Reaching the strong coupling regime of light-matter interaction has led to an impressive development in fundamental quantum physics and applications to quantum information processing. Latests advances in different quantum technologies, like superconducting circuits or semiconductor quantum wells, show that the ultrastrong coupling regime (USC) can also be achieved, where novel physical phenomena and potential computational benefits have been predicted. Nevertheless, the lack of effective decoupling mechanism in this regime has so far hindered control and measurement processes. Here, we propose a method based on parity symmetry conservation that allows for the generation and reconstruction of arbitrary states in the ultrastrong coupling regime of light-matter interactions. Our protocol requires minimal external resources by making use of the coupling between the USC system and an ancillary two-level quantum system. PMID- 26152810 TI - Performance enhancement of metal nanowire-based transparent electrodes by electrically driven nanoscale nucleation of metal oxides. AB - Solution-processed silver nanowire (AgNW) electrodes have been considered to be promising materials for next-generation flexible transparent conductive electrodes. Despite the fact that a single AgNW has extremely high conductivities, the high junction resistance between nanowires limits the performance of the AgNW matrix. Therefore, post-treatments are usually required to approach better NW-NW contact. Herein, we report a novel linking method that uses joule heating to accumulate sol-gel ZnO near nanowire junctions. The nanoscale ZnO nucleation successfully restrained the thermal instability of the AgNW under current injection and acted as an efficient tightening medium to realize good NW-NW contacts. A low process temperature (<50 degrees C), and thus low energy consumption, are required for ZnO nucleation. This made the use of substrates with very low operating temperatures, such as PET and PEN, feasible. The optimized AgNW transparent conductive electrodes (TCE) fabricated using this promising linking method exhibited a low sheet resistance (13 Omega sq(-1)), a high transmission (92% at 550 nm), a high figure of merit (FOM; up to sigmaDC/sigmaOp = 340) and can be applied to wide range of next-generation flexible optoelectronic devices. PMID- 26152811 TI - United States multicenter clinical trial of the cochlear nucleus hybrid implant system. AB - OBJECTIVES/HYPOTHESIS: To evaluate the safety and efficacy of acoustic and electric sound processing for individuals with significant residual low-frequency hearing and severe-to-profound high-frequency sensorineural hearing loss. STUDY DESIGN: Prospective, single-arm repeated measures, single-subject design. METHODS: Fifty individuals, >= 18 years old, with low-frequency hearing and severe high-frequency loss were implanted with the Cochlear Nucleus Hybrid L24 implant at 10 investigational sites. Preoperatively, subjects demonstrated consonant-nucleus-consonant word scores of 10% through 60% in the ear to be implanted. Subjects were assessed prospectively, preoperatively, and postoperatively on coprimary endpoints of consonant-nucleus-consonant words, AzBio sentences in noise, and self-assessment measures. RESULTS: Significant mean improvements were observed for coprimary endpoints: consonant-nucleus-consonant words (35.8 percentage points) and AzBio sentences in noise (32.0 percentage points), both at P < 0.001. Ninety-six percent of subjects performed equal or better on speech in quiet and 90% in noise. Eighty-two percent of subjects showed improved performance on speech in quiet and 74% in noise. Self-assessments were positive, corroborating speech perception results. CONCLUSION: The Nucleus Hybrid System provides significant improvements in speech intelligibility in quiet and noise for individuals with severe high-frequency loss and some low-frequency hearing. This device expands indications to hearing-impaired individuals who perform poorly with amplification due to bilateral high-frequency hearing loss and who previously were not implant candidates. PMID- 26152812 TI - Glucosamine anchored cancer targeted nano-vesicular drug delivery system of doxorubicin. AB - BACKGROUND: Efficacy of an anticancer drug is challenged by severe adverse effects persuaded by the drug itself; hence designing a tumour targeted delivery system is chosen as an objective of this research work. PURPOSE: We propose, glucose transporter targeting ligand, i.e. synthesised N-lauryl glucosamine (NLG) anchored doxorubicin (DOX) in niosomal formulation. METHODS: Synthesised NLG was incorporated into niosomal formulation of DOX using Span 60 as surfactant, cholesterol as membrane stabilizer and dicetyl phosphate (DCP) as stabilizer. RESULTS: The formulation was stable with particle size of 110 +/- 5 nm, zeta potential -30 +/- 5 mV and entrapment efficiency approximately 95%. DSC and XRD pattern of freeze-dried formulation demonstrated encapsulation of DOX in niosomal formulation. Cytotoxicity of targeted niosomal formulation (IC50 = 0.830 ppm) was higher than non-targeted niosomal formulation (IC50 = 1.369 ppm) against B6F10 melanoma cell lines. In vitro cellular internalization revealed that targeted niosomal formulation was internalised more efficiently with higher cellular retention by cancer cells compared to the non-targeted niosomal formulation and free DOX. In vitro receptor binding and docking study of targeted niosomal formulation had shown the comparative association potential with glucose receptor. CONCLUSION: NLG anchored niosomal formulation of DOX with enhanced cytotoxicity, internalization and receptor binding potential has implication in targeted cancer therapy. PMID- 26152813 TI - Factors influencing cancer treatment decision-making by indigenous peoples: a systematic review. AB - OBJECTIVE: We aim to systematically review studies that identify factors influencing cancer treatment decision-making among indigenous peoples. METHODS: Following the outline suggested by the Preferred Reporting Items for Systematic Review and Meta-analysis, a rigorous systematic review and meta-synthesis were conducted of factors that influence cancer treatment decision-making by indigenous peoples. A total of 733 articles were retrieved from eight databases and a manual search. After screening the titles and abstracts, the full text of 26 articles were critically appraised, resulting in five articles that met inclusion criteria for the review. Because the five articles to be reviewed were qualitative studies, the Critical Appraisal Skills Program toolkit was used to evaluate the methodological quality. A thematic synthesis was employed to identify common themes across the studies. RESULTS: Multiple socio-economic and cultural factors were identified that all had the potential to influence cancer treatment decision-making by indigenous people. These factors were distilled into four themes: spiritual beliefs, cultural influences, communication and existing healthcare systems and structures. CONCLUSION: Although existing research identified multiple factors influencing decision-making, this review identified that quality studies in this domain are scarce. There is scope for further investigation, both into decision-making factors and into the subsequent design of culturally appropriate programmes and services that meet the needs of indigenous peoples. PMID- 26152814 TI - Should we screen for cognitive decline and dementia? AB - Due to increased life expectancy, the prevalence of cognitive decline related to neurodegenerative diseases and to non-neurological conditions is increasing in western countries. As with other diseases, the burden might be reduced through personalized interventions delivered at early stages of the disease. Thus, there is an increasing demand, from both social and healthcare systems, for instruments and strategies to recognize cognitive decline, and possibly distinguish the precursor of serious neurodegeneration from "benign senile forgetfulness" or the temporary consequences of illness or trauma. However, this goal faces both technical and ethical issues. In this article we deal with the following: (i) re definition of cognitive decline and its relationship with frailty definitions, starting from the recent work of international consensus groups for presymptomatic Alzheimer disease recognition; (ii) ethical problems concerning anonymous and personalized cognitive screening and the need for appropriate counselling; (iii) the need for more sensitive and specific tools to detect and distinguish pathological levels of cognitive decline and delineate the contribution of non-pathological decline to accumulated frailty impacts and (iv) the potential of the language domain and spontaneous speech analyses. PMID- 26152815 TI - Activated carbon derived from melaleuca barks for outstanding high-rate supercapacitors. AB - Activated carbon (AC) was prepared via carbonizing melaleuca bark in an argon atmosphere at 600 degrees C followed with KOH activation for high-rate supercapacitors. This AC electrode has a high capacitance of 233 F g(-1) at a scan rate of 2 mV s(-1) and an excellent rate capability of ~80% when increasing the sweep rate from 2 to 500 mV s(-1). The symmetric supercapacitor assembled by the above electrode can deliver a high energy density of 4.2 Wh kg(-1) with a power density of 1500 W kg(-1) when operated in the voltage range of 0-1 V in 1 M H2SO4 aqueous electrolyte while maintaining great cycling stability (less than 5% capacitance loss after 10 000 cycles at sweep rate of 100 mV s(-1)). All the outstanding electrochemical performances make this AC electrode a promising candidate for potential energy storage application. PMID- 26152817 TI - The Weakness of Stern Alcohol Control Policies. AB - AIMS: To test the total consumption model claiming that alcohol-related ill health can best be diminished by a policy of severe restrictions and high price. METHODS: The associations between an index measuring the severity of the alcohol policy, total alcohol consumption and number of disability-adjusted life years (DALYs) lost due to alcohol were compared in 30 OECD countries in 2005. RESULTS: No significant correlations were found between alcohol policy index, alcohol consumption and the number of DALYs due to alcohol use. In regression analysis, alcohol policy index and alcohol consumption were not related to alcohol-related DALYs. Excise tax rate was not related to alcohol-related DALYs (25 countries with tax rate data). CONCLUSIONS: These findings suggest that the total consumption model fails. Alcohol-related ill health seems to be mainly due to alcohol dependence, both clinical and subclinical, not to moderate drinking. PMID- 26152818 TI - Lacosamide in status epilepticus: Update on the TRENdS study. AB - Many patients with critical illness have been noted to have nonconvulsive seizures (NCSs) and nonconvulsive status epilepticus (NCSE). How aggressively these seizures should be treated is unclear. Many investigators feel that the morbidity of NCSs and NCSE is different from that of generalized convulsive status epilepticus (GCSE), so treatment should be less urgent. Consequently, many nonsedating AEDs have been used to treat NCSs and NCSE in patients with critical illness. Randomized, controlled trials demonstrating the efficacy of AEDs in NCSs and NCSE are lacking. The Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) study compared lacosamide to fosphenytoin in the treatment of NCSs. An update of the study is presented. This article is part of a Special Issue entitled "Status Epilepticus". PMID- 26152816 TI - Recent research on bioactive xanthones from natural medicine: Garcinia hanburyi. AB - Garcinia hanburyi, a tropical plant found in south Asia, has a special long history in the development of both medicine and art. This review mainly focuses on the pharmacy research of the bioactive compounds from the plant in recent years. Preparative and analysis separation methods were introduced. Moreover, the chemical structure of the isolated compounds was included. The studies of biological activities of the caged xanthones from the plant, including antitumor, anti-HIV-1, antibacterial, and neurotrophic activities, were reviewed in detail. Furthermore, the mechanisms of its antitumor activity were also reviewed. As mentioned above, some of the xanthones from G. hanburyi can be promising drug candidates, which is worth studying. However, we still need much evidence to prove their efficacy and safety. So, further research is critical for the future application of xanthones from G. hanburyi. PMID- 26152819 TI - Modeling diurnal hormone profiles by hierarchical state space models. AB - Adrenocorticotropic hormone (ACTH) diurnal patterns contain both smooth circadian rhythms and pulsatile activities. How to evaluate and compare them between different groups is a challenging statistical task. In particular, we are interested in testing (1) whether the smooth ACTH circadian rhythms in chronic fatigue syndrome and fibromyalgia patients differ from those in healthy controls and (2) whether the patterns of pulsatile activities are different. In this paper, a hierarchical state space model is proposed to extract these signals from noisy observations. The smooth circadian rhythms shared by a group of subjects are modeled by periodic smoothing splines. The subject level pulsatile activities are modeled by autoregressive processes. A functional random effect is adopted at the pair level to account for the matched pair design. Parameters are estimated by maximizing the marginal likelihood. Signals are extracted as posterior means. Computationally efficient Kalman filter algorithms are adopted for implementation. Application of the proposed model reveals that the smooth circadian rhythms are similar in the two groups but the pulsatile activities in patients are weaker than those in the healthy controls. PMID- 26152820 TI - Interactive Effects of Growth Regulators, Carbon Sources, pH on Plant Regeneration and Assessment of Genetic Fidelity Using Single Primer Amplification Reaction (SPARS) Techniques in Withania somnifera L. AB - An improved and methodical in vitro shoot morphogenic approach through axillary bud multiplication was established in a drug yielding plant, Withania somnifera L. Effects of plant growth regulators [6-benzyladenine (BA), kinetin (Kin), 2 isopentenyladenine (2iP), and thidiazuron (TDZ)] either singly or in combination with alpha-napthalene acetic acid (NAA), indole-3-butyric acid (IBA), and indole 3-acetic acid (IAA) in Murashige and Skoog (MS) medium were tested. The highest regeneration frequency (90 %) with optimum number of shoots (32 +/- 0.00)/explant were obtained on MS medium fortified with 2.5 MUM 6-benzyladenine (BA) and 0.5 MUM NAA and 30 g/l sucrose at pH 5.8. Among the tried TDZ concentrations, 0.5 MUM resulted in maximum number of shoots (20.4 +/- 0.40)/explant after 4 weeks of exposure. The proliferating shoot cultures established by repeated subculturing of the mother explants on the hormone-free medium produced the highest shoot number (29.4 +/- 0.40) with shoot length (6.80 +/- 0.12 cm)/explant at fourth subculture passage, which a decline in shoot proliferation was recorded. Different concentrations of NAA were tested for ex vitro rooting of microshoots. The maximum percentage of rooting 100 % with maximum roots (18.3 +/- 0.1) was achieved in soilrite when basal portion of the microshoots were treated with 200 MUM (NAA) for 15 min per shoot. The plantlets went through hardening phase in a growth chamber, prior to ex vitro transfer. The PCR-based single primer amplification reaction (SPAR) methods which include random amplified polymorphic DNA (RAPD) and direct amplification of minisatellite DNA (DAMD) markers has been used for assessment of genetic stability of micropropagated plantlets. No variation was observed in DNA fingerprinting patterns among the micropropagated and the donor plants illustrating their genetic uniformity. PMID- 26152821 TI - Optimized Transformation of Newly Constructed Escherichia coli-Clostridia Shuttle Vectors into Clostridium beijerinckii. AB - Three Escherichia coli-Clostridia shuttle vectors, pKBA411-MCS, pKBE411-MCS, and pKBM411-MCS, which contain p15A, ColE1, and pMB1 origins for replication in E. coli, respectively, along with the pAMB origin for replication in C. beijerinckii, were constructed and examined for their transformation efficiencies into Clostridium beijerinckii NCIMB8052. The transformation condition of pKBM411 MCS, which was optimized by varying resistance, buffer composition, and DNA concentration, was further employed for the transformation of the other plasmids, pKBA411-MCS and pKBE411-MCS into C. beijerinckii. It was found out that transformation efficiency is highly dependent on the origin of replication. The highest transformation efficiency of 7.44 * 10(3) colony-forming units per microgram of DNA was obtained at 5.0 kV cm(-1) field strength, 200 Omega resistance, 270 mM sucrose concentration, 150 ng MUg(-1), and 3.0 MUg DNA using pKBM411-MCS having pMB1 and pAMB origins of replication. The application of the newly constructed vector system was also investigated by introducing the putative alcohol dehydrogenase gene of C. beijerinckii. PMID- 26152822 TI - The microwave-assisted solvothermal synthesis of a crystalline two-dimensional covalent organic framework with high CO2 capacity. AB - We report the synthesis of a two-dimensional enamine-linked covalent organic framework (COF) using a rapid microwave-assisted solvothermal method in significantly less time and high yield under a relatively low temperature. This COF was found to have a high crystallinity, high stability, high BET surface area, and a high CO2 capacity and adsorption selectivity of CO2/N2. PMID- 26152823 TI - Association of Maternal and Infant Salivary Testosterone and Cortisol and Infant Gender With Mother-Infant Interaction in Very-Low-Birthweight Infants. AB - Male very-low-birthweight (VLBW) infants are more prone than females to health and developmental problems and less positive mother-infant interactions. Because gender differences in brain development and social relationships suggest hormonal influences on quality of mother-infant interaction, the authors explored the associations of maternal and infant salivary testosterone and cortisol levels with mother-infant interactions in the sample as a whole and by gender, after controlling for covariates. Data were collected prospectively from 62 mothers and their VLBW infants through infant record review, maternal interview, biochemical measurement of both mothers and infants, and observation of mother-infant interactions at 40 weeks postmenstrual age and at three and six months corrected age. Infants' positive interactions increased and mothers' decreased from three to six months. In generalized estimating equation (GEE) analyses, after controlling for covariates, higher maternal testosterone and infant cortisol were associated with more positive and more frequent maternal interactive behaviors. In GEE analyses by infant gender, after controlling for covariates, effects of maternal and infant hormone levels became more significant, especially on infants' interactive behaviors. Based on these preliminary findings, among VLBW infants, males with high testosterone are expected to have less positive mother infant interactions than males with low testosterone or female infants. PMID- 26152824 TI - Time-Resolved Analysis of Cytosolic and Surface-Associated Proteins of Staphylococcus aureus HG001 under Planktonic and Biofilm Conditions. AB - Staphylococcal biofilms are associated with persistent infections due to their capacity to protect bacteria against the host's immune system and antibiotics. Cell-surface-associated proteins are of great importance during biofilm formation. In the present study, an optimized biotinylation approach for quantitative GeLC-MS-based analysis of the staphylococcal cell-surface proteome was applied and the cytoplasmic protein fraction was analyzed to elucidate proteomic differences between colony biofilms and planktonic cells. The experimental setup enabled a time-resolved monitoring of the proteome under both culture conditions and the comparison of biofilm cells to planktonic cells at several time points. This allowed discrimination of differences attributed to delayed growth phases from responses provoked by biofilm conditions. Biofilm cells expressed CcpA-dependent catabolic proteins earlier than planktonic cells and strongly accumulated proteins that belong to the SigB stress regulon. The amount of the cell-surface protein and virulence gene regulator Rot decreased within biofilms and MgrA-dependent regulations appeared more pronounced. Biofilm cells simultaneously up-regulated activators (e.g., SarZ) as well as repressors (e.g., SarX) of RNAIII. A decreased amount of high-affinity iron uptake systems and an increased amount of the iron-storage protein FtnA possibly indicated a lower demand of iron in biofilms. PMID- 26152827 TI - Correlation of matrix metalloproteinase-2 single nucleotide polymorphisms with the risk of small vessel disease (SVD). AB - BACKGROUND: Maladjustment of matrix metalloproteinases (MMPs) results in cerebral vasculature and blood-brain barrier dysfunction, which is associated with small vessel disease (SVD). This study was to aim at evaluating correlations between matrix metalloproteinase-2 and 9 single nucleotide polymorphisms and the risk of SVD. METHODS: A total of 178 patients with SVD were enrolled into this study via Nanjing Stroke Registry Program (NSRP) from January 2010 to November 2011. SVD patients were further subtyped as isolated lacunar infarction (ILI, absent or with mild leukoaraiosis) and ischemic leukoaraiosis (ILA, with moderate or severe leukoaraiosis) according to the Fazekas scale. 100 age- and gender-matched individuals from outpatient medical examination were recruited as the control group. The genotypes of MMP-2-1306 T/C and MMP-9-1562 C/T were determined by the TaqMan method. RESULTS: Of 178 SVD patients, 86 and 92 patients were classified as ILI and ILA, respectively. Comparison analysis between SVD patients and controls revealed a significant correlation between SVD and hypertension, as well as a prevalence of hypertension in ILA. Further genotype analysis showed that the frequency of MMP-2-1306 CC genotype was higher in ILA patients than in controls (P=0.009, chi(2) test; P=0.027, the multiple test with Bonferroni correction). Finally, logistic regression analysis with adjustment of age, sex and vascular risk factors showed that the MMP-2-1306 T/C polymorphism was an independent predictor for ILA (OR: 2.605; 95% confidence interval [CI], 1.067-6.364; P=0.036). CONCLUSION: Our findings suggest that the MMP-2-1306 T/C polymorphism is a direct risk factor for ILA. PMID- 26152828 TI - Sevoflurane post-conditioning protects primary rat cortical neurons against oxygen-glucose deprivation/resuscitation via down-regulation in mitochondrial apoptosis axis of Bid, Bim, Puma-Bax and Bak mediated by Erk1/2. AB - Temporal post-conditioning helps provide neuroprotection against brain injury secondary to ischemia-reperfusion and is considered an effective intervention, but the exact mechanism of sevoflurane post-conditioning is unclear. The essential axis involves activator Bid, Bim, Puma (BH3s), Bax, and Bak; activates the mitochondrial death program; and might be involved in a cell death signal. Extracellular signal-related kinases 1/2 (Erk1/2) play a pivotal role in cell growth and proliferation. We hypothesized that sevoflurane post-conditioning might inhibit Bid, Bim, Puma, Bax, and Bak expression and is activated by phosphor-Erk1/2 to decrease neuronal death. To test this hypothesis, we exposed primary cortical neuron cultures to oxygen-glucose deprivation for 1h, along with resuscitation for 24h (OGD/R). MTT assays, propidium iodide uptake (PI), JC-1 fluorescence, and Western blot indicated the following: decreased cell viability (P<0.05); increased cell death (P<0.05); decreased mitochondrial membrane potential (P<0.05); and decreased Bid, Bim, Puma, Bax, and Bak expression with OGD/R exposure. Inhibition of Erk1/2 phosphorylation could attenuate sevoflurane post-conditioning that mediated an increase in neuronal viability and mitochondrial membrane potential, as well as a decrease in cell death and Bid, Bim, Puma, Bax, and Bak expression after OGD/R treatment. The results demonstrated that sevoflurane post-conditioning caused a marked decrease in cortical neuronal death secondary to OGD/R exposure through the downregulation of the mitochondrial apoptosis axis involving Bid, Bim, Puma, Bax, and Bak that was mediated by the phosphorylation/activation of Erk1/2. PMID- 26152829 TI - Use of the King-Devick test for sideline concussion screening in junior rugby league. AB - AIM: To determine whether the King-Devick (K-D) test used as a sideline test in junior rugby league players over 12 matches in a domestic competition season could identify witnessed and incidentally identified episodes of concussion. METHODS: A prospective observational cohort study of a club level junior rugby league team (n=19) during the 2014 New Zealand competition season involved every player completing two pre-competition season baseline trials of the K-D test. Players removed from match participation, or who reported any signs or symptoms of concussion were assessed on the sideline with the K-D test and referred for further medical assessment. Players with a pre- to post-match K-D test difference >3s were referred for physician evaluation. RESULTS: The baseline test-retest reliability of the K-D test was high (rs=0.86; p<0.0001). Seven concussions were medically identified in six players who recorded pre- to post-match K-D test times greater than 3s (mean change of 7.4s). Post-season testing of players demonstrated improvement of K-D time scores consistent with learning effects of using the K-D test (67.7s vs. 62.2s). DISCUSSION: Although no witnessed concussions occurred during rugby play, six players recorded pre- to post-match changes with a mean delay of 4s resulting in seven concussions being subsequently confirmed post-match by health practitioners. All players were medically managed for a return to sports participation. CONCLUSION: The K-D test was quickly and easily administered making it a practical sideline tool as part of the continuum of concussion assessment tools for junior rugby league players. PMID- 26152830 TI - Pregnancy course in patients with intrahepatic cholestasis of pregnancy treated with very low doses of ursodeoxycholic acid. AB - OBJECTIVE: Ursodeoxycholic acid (UDCA) has been proposed as the optimal pharmacological treatment for intrahepatic cholestasis of pregnancy (ICP). The lowest effective dosage of UDCA in women with ICP has not been established. The objective is to determine the risk of adverse pregnancy outcomes resulting from ICP and to measure changes in liver function parameters and pruritus severity in ICP patients treated with low doses of UDCA. MATERIAL AND METHODS: ICP was diagnosed in 203 patients on the basis of pruritus and elevated liver biochemical parameters. Patients with total bile acids (TBA) >= 10 MUmol/l (n = 157) received UDCA (300-450 mg/day; 4-6 mg/kg/day) until delivery. Maternal and fetal outcomes of women with ICP were compared with 100 patients without cholestasis. Patients with ICP were hospitalized for treatment and fetal surveillance. RESULTS: There was no correlation between fetal and neonatal complication rates in ICP patients and biochemical markers of cholestasis. Significant declines in serum TBA (p = 0.003), bilirubin concentration (p = 0.026) and aminotransferase activity (p < 0.001) were observed during treatment with low doses of UDCA. Moreover, severity of pruritus was ameliorated during the 2 weeks of therapy (p = 0.037). A total of 17 patients (10.9%) did not respond to treatment. CONCLUSIONS: UDCA at low doses improved biochemical markers and clinical symptoms in almost 90% of ICP patients. PMID- 26152831 TI - Examinations of ascites from prophylactic drains can predict intra-abdominal infections after living donor liver transplantation. AB - Studies suggest that prophylactic intra-abdominal drains are unnecessary for cadaveric liver transplantation using whole liver grafts because there is no benefit from drainage. However, no studies have investigated on the necessity of prophylactic drains after LDLT using split-liver grafts or reduced-liver grafts, which may present a high risk of post-transplant intra-abdominal infections. This retrospective study investigated whether the ascitic data on POD 5 after LDLT can predict intra-abdominal infections and on the post-transplant management of prophylactic drains. Between March 2008 and March 2013, 90 LDLTs were performed. We assessed the number of ascitic cells, biochemical examinations, and cultivation tests at POD1 and POD5. The incidence rates of post-transplant intra abdominal infections were 24.4%. The multivariate analysis showed that left lobe and S2 monosegment grafts were a significant risk factor for intra-abdominal infections (p = 0.006). The patients with intra-abdominal infections had significantly higher acsitic LDH levels and the positive rate of ascitic culture at POD5 in comparison with patients without infections (p < 0.001 and p = 0.014, respectively). LDLT using left lobe and S2 monosegment grafts yields a high risk for post-transplant intra-abdominal infections, and ascitic LDH and cultivation tests at POD5 via prophylactic drains can predict intra-abdominal infections. PMID- 26152832 TI - Preliminary investigation of differential tapelifting for sampling forensically relevant layered deposits. AB - The analysis of DNA mixtures can be problematic, especially when in trace quantities such as when a biological sample is deposited onto a substrate which contains background DNA (for example, in the case of touch DNA deposited onto a garment containing the wearer's DNA). We conducted a preliminary investigation into the possibility of removing such multi-donor deposits layer by layer using a differential tape-lifting method. Two types of tape were tested using two different numbers of applications for sampling layered deposits of touch DNA/touch DNA and touch DNA/saliva, both on the same polyester-cotton plain woven material. The data showed that there was no significant increase in the ratio of secondary to primary deposit when sampled in this manner, compared to direct extraction from cuttings of the touched fabric. A similar result was also obtained even when the deposits were on opposing surfaces of the fabric and the sampling was carried out on the secondary deposit side. These findings indicate that biological material, whether touch DNA or saliva, does not predominantly remain on the side of the fabric on which it is deposited (at least for plain woven polyester-cotton). They also highlight the importance of considering substrate properties when making assumptions as to the resulting location of biological materials from a deposition event, and the necessity to conduct further research on the interactions between substrates and deposits. PMID- 26152833 TI - Bone-anchored hearing implants in single-sided deafness patients: Long-term use and satisfaction by gender. AB - OBJECTIVES/HYPOTHESIS: To examine the long-term satisfaction and possible effects of gender in patients with single-sided deafness (SSD) who underwent bone anchored hearing implant (BAHI) surgery. STUDY DESIGN: Retrospective case-control study. METHODS: All (n = 145) consecutive SSD patients fitted with a BAHI between January 2001 and October 2011 were asked to complete a questionnaire consisting of the Abbreviated Profile of Hearing Aid Benefit (APHAB), the Communication Profile for the Hearing Impaired (CPHI), and the SSD questionnaire. RESULTS: Twenty-three of the 135 responding patients (17%) reported discontinuation of the device over an average follow-up time of 61.7 months. No significant differences were found in the degree of disability or coping between men and women, according to the APHAB and CPHI scores. Improvement in quality of life and appreciation of the BAHI were not affected by gender, age, directional hearing ability, and handling of the device. The appearance of the device positively affected their appreciation. At the mean follow-up time of 117 months, 69.2% was using their BAHI. In the domains background noise, reverberant surroundings, and aversion to sounds, the mean APHAB scores were significantly changed at 3 months, 1 year, and 10 years after implantation. CONCLUSION: Our study examined the results of BAHI use in SSD patients over a relatively long follow-up period, with an average of 5 years. The majority of users (83%) were satisfied with the device. No significant gender differences were in terms of reported appreciation, hearing disability, or coping with a BAHI. LEVEL OF EVIDENCE: 3b. PMID- 26152834 TI - Characteristics of clinical trials that require participants to be fluent in English. AB - BACKGROUND/AIMS: Diverse samples in clinical trials can make findings more generalizable. We sought to characterize the prevalence of clinical trials in the United States that required English fluency for participants to enroll in the trial. METHODS: We randomly chose over 10,000 clinical trial protocols registered with ClinicalTrials.gov and examined the inclusion and exclusion criteria of the trials. We compared the relationship of clinical trial characteristics with English fluency inclusion requirements. We merged the ClinicalTrials.gov data with US Census and American Community Survey data to investigate the association of English-language restrictions with ZIP-code-level demographic characteristics of participating institutions. We used Chi-squared tests, t-tests, and logistic regression models for analyses. RESULTS: English fluency requirements have been increasing over time, from 1.7% of trials having such requirements before 2000 to 9.0% after 2010 (p < 0.001 from Chi-squared test). Industry-sponsored trials had low rates of English fluency requirements (1.8%), while behavioral trials had high rates (28.4%). Trials opening in the Northeast of the United States had the highest regional English requirement rates (10.7%), while trials opening in more than one region had the lowest (3.3%, p<0.001). Since 1995, trials opening in ZIP codes with larger Hispanic populations were less likely to have English fluency requirements (odds ratio=0.92 for each 10% increase in proportion of Hispanics, 95% confidence interval=0.86-0.98, p=0.013). Trials opening in ZIP codes with more residents self-identifying as Black/African American (odds ratio=1.87, 95% confidence interval=1.36-2.58, p<0.001 for restricted cubic spline term) or Asian (odds ratio=1.16 for linear term, 95% confidence interval=1.07-1.25, p<0.001) were more likely to have English fluency requirements. ZIP codes with higher poverty rates had trials with more English-language restrictions (odds ratio=1.06 for a 10% poverty rate increase, 95% confidence interval=1.001-1.11, p=0.045). There was a statistically significant interaction between year and intervention type, such that the increase in English fluency requirements was more common for some interventions than for others. CONCLUSION: The proportion of clinical trials registered with ClinicalTrials.gov that have English fluency requirements for study inclusion has been increasing over time. English-language restrictions are associated with a number of characteristics, including the demographic characteristics of communities in which the sponsoring institutions are located. PMID- 26152835 TI - Developing training for Data Safety Monitoring Board members: A National Institute of Allergy and Infectious Diseases case study. AB - BACKGROUND: Data Safety Monitoring Boards primarily review accumulating data on clinical trials and provide recommendations to sponsors on whether a protocol should continue as planned, be modified, or be terminated. Data Safety Monitoring Boards often provide their recommendations based upon accumulating data to which only their members are given access. Despite the substantial responsibilities assumed by Data Safety Monitoring Board members, there is limited information in the literature about the unique knowledge they must possess and, consequently, the training content needs that are required in order for them to fulfill their obligations. PURPOSE: This article describes how the National Institute of Allergy and Infectious Diseases identified the knowledge that Data Safety Monitoring Board members should acquire and the computer-based training they developed to address the learning needs of the National Institute of Allergy and Infectious Diseases assembled Data Safety Monitoring Board members. METHODS: The National Institute of Allergy and Infectious Diseases conducted a comprehensive literature search and interviewed Data Safety Monitoring Board subject matter experts, including Data Safety Monitoring Board members and chairs from academic institutions, pharmaceutical companies, and the National Institutes of Health to (1) assess whether Data Safety Monitoring Board training is an identified need, (2) evaluate whether Data Safety Monitoring Board training has been developed, and (3) formulate suitable learning objectives. Data Safety Monitoring Board training modules were developed based on the identified learning objectives identified from the interviews. RESULTS: Three Data Safety Monitoring Board training modules were developed and formatted for web-based access, which is free of charge to the public at https://dsmblearningcenter.niaid.nih.gov. The modules include the following: an introduction to the objectives and purpose of Data Safety Monitoring Boards, the organization and responsibilities of Data Safety Monitoring Boards, and a review of statistical topics. LIMITATIONS: The complex concepts that Data Safety Monitoring Board members must apply to their deliberations and decisions require practice and application that come through hands-on experience. To build competency in the Data Safety Monitoring Board member role, not only does a member need to understand these complex concepts but also the member must have the opportunity to practice and apply this knowledge to real-life situations. Additional resources to facilitate practice and application of the complex issues that Data Safety Monitoring Boards deal with should be considered. The computer-based training is targeted to new and inexperienced Data Safety Monitoring Board members. Ongoing learning opportunities should be developed for experienced Data Safety Monitoring Board members. Non-English training must also be considered. CONCLUSION: The National Institute of Allergy and Infectious Diseases identified that training is not widely available for Data Safety Monitoring Board members to build the unique knowledge and skills necessary to serve on Data Safety Monitoring Boards. Consequently, National Institute of Allergy and Infectious Diseases developed publicly available web based Data Safety Monitoring Board training modules for new or inexperienced members. Additional tools and resources are needed to help Data Safety Monitoring Board members acquire the knowledge and skills to serve their critical function in clinical research and to maximize research participant protections. PMID- 26152836 TI - Frequency of O6-methylguanine-DNA methyltransferase promoter methylation in cytological samples from small cell lung cancer. AB - BACKGROUND: In a phase II study for patients with relapsed small cell lung cancer (SCLC), the administration of Temozolomide, an alkylating agent used in gliomas and anaplastic astrocytoma, showed a effective activity when O(6) -methylguanine DNA methyltransferase (MGMT) gene promoter was methylated. METHODS: We tested the feasibility of MGMT promoter status evaluation in small biopsies and cytological specimens routinely processed for diagnostic purposes. We tested samples from 56 patients with SCLC: 30 tissue biopsies, 17 fine-needle aspiration biopsy, 8 bronchial washing, and 1 was a sputum. Biopsies and fine-needle aspiration biopsy were fixed in formalin, bronchial washing and sputum in Dubosq Brazil. DNA was extracted after macrodissection of the areas containing the maximum number of cancer cells. MGMT promoter methylation status was assessed by methylation specific PCR. RESULTS: Methylation analysis was obtained in 54 samples (54/56) and failed in two bronchial wash. MGMT promoter was methylated in 35.2% of the cases without any significant difference between histological and cytological samples (37.9% vs. 32%). CONCLUSION: MGMT promoter methylation is present in SCLC and cytological samples are perfectly adequate for methylation analysis, even if they were taken during routine diagnostic procedures, using different fixative and with low number and percentage of cancer cells. PMID- 26152837 TI - The Added Value of Collecting Information on Pain Experience When Predicting Time on Benefits for Injured Workers with Back Pain. AB - Objectives Some injured workers with work-related, compensated back pain experience a troubling course in return to work. A prediction tool was developed in an earlier study, using administrative data only. This study explored the added value of worker reported data in identifying those workers with back pain at higher risk of being on benefits for a longer period of time. Methods This was a cohort study of workers with compensated back pain in 2005 in Ontario. Workplace Safety and Insurance Board (WSIB) data was used. As well, we examined the added value of patient-reported prognostic factors obtained from a prospective cohort study. Improvement of model fit was determined by comparing area under the curve (AUC) statistics. The outcome measure was time on benefits during a first workers' compensation claim for back pain. Follow-up was 2 years. Results Among 1442 workers with WSIB data still on full benefits at 4 weeks, 113 were also part of the prospective cohort study. Model fit of an established rule in the smaller dataset of 113 workers was comparable to the fit previously established in the larger dataset. Adding worker rating of pain at baseline improved the rule substantially (AUC = 0.80, 95 % CI 0.68, 0.91 compared to benefit status at 180 days, AUC = 0.88, 95 % CI 0.74, 1.00 compared to benefits status at 360 days). Conclusion Although data routinely collected by workers' compensation boards show some ability to predict prolonged time on benefits, adding information on experienced pain reported by the worker improves the predictive ability of the model from 'fairly good' to 'good'. In this study, a combination of prognostic factors, reported by multiple stakeholders, including the worker, could identify those at high risk of extended duration on disability benefits and in potentially in need of additional support at the individual level. PMID- 26152838 TI - Oral pseudoephedrine decreases the rate of transmucosal nitrous oxide exchange for the middle ear. AB - OBJECTIVES/HYPOTHESIS: Determine if oral treatment with a vasoconstrictor decreases the blood to middle ear exchange rate of the perfusion-limited gas, nitrous oxide (N2O). STUDY DESIGN: Randomized, double-blind, crossover study. METHODS: Ten adult subjects with and 10 without past middle ear disease completed paired experimental sessions, identical except for oral treatment with either pseudoephedrine hydrochloride or lactose placebo. At each session, subjects were fitted with a nonrebreathing mask and breathed room air for 20 minutes (acclimation period), 50% N2O:50% O2 for 20 minutes (experimental period), and 100% O2 for 10 minutes (recovery period). Throughout, heart rate, blood pressure, and O2 saturation were monitored, and bilateral middle ear pressures were recorded by tympanometry every minute. The primary outcome was the slope of the middle ear pressure-time function for the experimental period, which estimates the volume N2O exchange rate. Using repeated measures analysis of variance, the effects of group (disease history), treatment (active vs. placebo), and period (1 vs. 2) on the recorded vital signs, and of group, treatment, and ear (left/right) on the middle ear pressure-time slope were evaluated for statistical significance. RESULTS: Statistically significant effects of period on O2 saturation (period 2 > period 1) and of treatment on heart rate (active > placebo) were documented. Only treatment was statistically significant for the middle ear pressure-time slope, with a shallower slope characterizing the active treatment session. CONCLUSIONS: The volume exchange rate across the middle ear mucosa of perfusion-limited gases can be modulated pharmacologically. Theoretically, similar drugs can be used to reduce the requisite eustachian tube opening efficiency for adequate middle ear pressure regulation. LEVEL OF EVIDENCE: 1b. PMID- 26152840 TI - High-yield synthesis and optical properties of g-C3N4. AB - Graphitic carbon nitride (g-C3N4), a metal-free semiconductor with a band gap of 2.7 eV, has received considerable attention owing to its fascinating photocatalytic performances under visible-light. g-C3N4 exhibits high thermal and chemical stability and non-toxicity such that it has been considered as the most promising photocatalyst for environmental improvement and energy conservation. Hence, it is of great importance to obtain high-quality g-C3N4 and gain a clear understanding of its optical properties. Herein, we report a high-yield synthesis of g-C3N4 products via heating of high vacuum-sealed melamine powder in an ampoule at temperatures between 450 and 650 degrees C. Using transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), electron energy loss spectroscopy (EELS), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), the chemical composition and crystallization of the as-produced g-C3N4 are demonstrated. A systematic optical study of g-C3N4 is carried out with several approaches. The optical phonon behavior of g-C3N4 is revealed by infrared and Raman spectroscopy, and the emission properties of g-C3N4 are investigated using photoluminescence (PL) spectroscopy, while the photocatalytic properties are explored by the photodegradation experiment. PMID- 26152839 TI - Neuroligin-2 Expression in the Prefrontal Cortex is Involved in Attention Deficits Induced by Peripubertal Stress. AB - Emerging evidence indicates that attention deficits, which are frequently observed as core symptoms of neuropsychiatric disorders, may be elicited by early life stress. However, the mechanisms mediating these stress effects remain unknown. The prefrontal cortex (PFC) has been implicated in the regulation of attention, including dysfunctions in GABAergic transmission, and it is highly sensitive to stress. Here, we investigated the involvement of neuroligin-2 (NLGN 2), a synaptic cell adhesion molecule involved in the stabilization and maturation of GABAergic synapses, in the PFC in the link between stress and attention deficits. First, we established that exposure of rats to stress during the peripubertal period impairs attention in the five-choice serial reaction time task and results in reductions in the GABA-synthesizing enzyme glutamic acid decarboxylase in different PFC subregions (ie, prelimbic (PL), infralimbic, and medial and ventral orbitofrontal (OFC) cortex) and in NLGN-2 in the PL cortex. In peripubertally stressed animals, NLGN-2 expression in the PL and OFC cortex correlated with attention measurements. Subsequently, we found that adeno associated virus-induced rescue of NLGN-2 in the PFC reverses the stress-induced attention deficits regarding omitted trials. Therefore, our findings highlight peripuberty as a period that is highly vulnerable to stress, leading to the development of attention deficits and a dysfunction in the PFC GABAergic system and NLGN-2 expression. Furthermore, NLGN-2 is underscored as a promising target to treat stress-induced cognitive alterations, and in particular attentional deficits as manifested by augmented omissions in a continuous performance task. PMID- 26152841 TI - A systematic review and meta-analysis on acoustic voice parameters after uncomplicated thyroidectomy. AB - BACKGROUND: Postthyroidectomy voice changes are common even without apparent laryngeal nerve injury. Our study evaluated the impact of open cervical thyroidectomy on five acoustic voice parameters in the early (< 3 months) and late (>= 3 months) postoperative periods. METHODS: A systematic review was performed to identify studies that quantitatively assessed voice quality by acoustic voice analysis before and after thyroidectomy. Parameters included average fundamental frequency (F0 , Hz), jitter (%), shimmer (%), noise-to harmonic ratio (NHR), and maximum phonation time (MPT) (in secs). Meta-analysis was performed using both fixed- and random-effects models. RESULTS: A total of 896 patients were analyzed. Relative to baseline, F0 significantly worsened in the early period (from 194.9 +/- 34.9 Hz to 188.0 +/- 34.0 Hz, P = 0.001). This was equivalent to a quarter-tone loss (P = 0.004). Shimmer (from 3.15 +/- 1.59% to 3.19 +/- 1.70%, P = 0.040) and MPT (from 17.9 secs to 16.7 secs, P = 0.046) also worsened in the early period, whereas jitter and NHR remained unchanged in the early and late periods. Males suffered greater deterioration in F0 (from 120.6 +/- 18.8 Hz to 111.0 +/- 18.5 Hz, P = 0.048) and in NHR (from 0.12 +/- 0.02 to 0.16 +/- 0.03, P = 0.019) than females in the early period. Four of the five acoustic parameters (F0 , jitter, shimmer, and NHR) significantly worsened after total thyroidectomy (TT) and not after lesser resection. CONCLUSION: F0 , shimmer, and MPT significantly worsened in the early and not in the late postoperative period. F0 impairment was perceptually significant. Males and those undergoing TT suffered greater voice impairment than their counterparts during the early period. PMID- 26152842 TI - Factors associated with quality of life among family caregivers of terminally ill cancer patients. AB - OBJECTIVE: Limited research has examined the quality of life (QOL) and its correlates among family caregivers (FCs) during the final stage of terminal cancer. The purpose of this study was to investigate the determinants of overall QOL and its subdomains among Korean FCs at the very end of life. METHODS: For this cross-sectional study, we enrolled 299 FCs of terminal cancer patients from seven palliative care units. To assess FCs' QOL and its predictors, we used the Caregiver Quality Of Life Index-Cancer, which contains four domains. Possible determinants of caregiver QOL were categorized into patient, caregiver, and environmental factors. A multiple regression model was used to identify factors associated with FCs' QOL. RESULTS: Variance in each Caregiver Quality Of Life Index-Cancer domain was explained by different factors. FCs of younger patient felt more burden but were more likely to adapt positively. Emotional distress of FCs was strongly associated with total QOL, burdensomeness, and disruptiveness. Positive adaptation was related to more visits for care, FCs' religiousness, more social support, and satisfactory perceived quality of care. Financial concerns were more likely in married FCs, FCs with less social support, or low incomes. CONCLUSION: Emotional distress of FCs was the most important factor determining the overall and negative aspects of FCs' QOL, whereas various environmental factors were associated with positive coping. Appropriate support programs directed at these factors are needed to maintain and improve FCs' QOL. PMID- 26152843 TI - Effect of preoperative colonoscopic tattooing on lymph node harvest in T1 colorectal cancer. AB - OBJECTIVE: This study aimed to identify the impact of preoperative colonoscopic tattooing (PCT) on lymph node harvest in T1 colorectal cancer patients. MATERIAL AND METHODS: One hundred and forty-three patients were included who underwent curative resection and were diagnosed with T1 colorectal cancer. These patients were categorized into the tattooing group and the non-tattooing group depending on whether preoperative India ink tattooing was done. Clinicopathological findings and lymph node harvest were compared between the two groups. RESULTS: The median number of lymph nodes examined was 18 in the tattooing group and 13 in the non-tattooing group (p < 0.001). The rate of adequate lymph node harvest (retrieval of more than 12 lymph nodes) was higher in the tattooing group than that in the non-tattooing group (83.7 vs. 58.5 %, p = 0.002). The PCT was significantly associated with adequate lymph node harvest in multivariate analysis (hazard ratio, 3.8; 95 % confidence interval, 1.5-9.2; p = 0.003). Among the 40 patients who showed at least one carbon particle-containing lymph nodes, the positive lymph node rate was not different between carbon-containing LNs (0.9 %) and non-carbon-containing LNs (1.7 %). CONCLUSIONS: PCT was associated with higher lymph node yield in T1 colorectal cancer. It is questionable if tattooing has additional detection power as a sentinel lymph node mapping tool in T1 colorectal cancer. PMID- 26152844 TI - Endoscopic follow-up after surgery for colorectal cancer. AB - OBJECTIVE: Follow-up surgery for colorectal cancer is recommended. The yield of endoscopy is unknown and was therefore studied. METHODS: Patients with colorectal cancer in the years 2003, 2004 and 2005 were included. Evaluation was done in July 2014. RESULTS: Cancer was diagnosed in 267 patients. These were divided into three groups: group 1-still alive (n = 88), group 2-died within 1 year after diagnosis (n = 67), and group 3-died more than 1 year after diagnosis (n = 112). Patients in group 3 showed a trend towards non-cancer-related death (p = 0.06). Endoscopic follow-up was done in 101 patients (37.6 %). Patients still alive underwent more often follow-up colonoscopy (p < 0.001). Patients still alive had more often synchronous polyps detected during index endoscopy compared with patients of groups 2 and 3 (p = 0.03). Follow-up revealed more often new polyp(s) (p = 0.006). If no polyps were seen during the time of diagnosing cancer, follow up endoscopy detected polyp(s) in 26 % of cases. Two newly developed cancers in group 1 and three in group 3 were diagnosed. CONCLUSION: Endoscopic follow-up after curative surgery for colorectal cancer has a high diagnostic yield. Whether detection and removal of polyps increases survival is not yet clear. PMID- 26152846 TI - Mutational Heterogeneity of MED23 Gene in Colorectal Cancers. PMID- 26152845 TI - A novel pathogenic RBP-3 peptide reveals epitope spreading in persistent experimental autoimmune uveoretinitis. AB - Experimental autoimmune uveoretinitis (EAU) in the C57BL/6J mouse is a model of non-infectious posterior segment intraocular inflammation that parallels clinical features of the human disease. The purpose of this study was to analyse the immune response to the four murine subunits of retinol binding protein-3 (RBP-3) to identify pathogenic epitopes to investigate the presence of intramolecular epitope spreading during the persistent inflammation phase observed in this model of EAU. Recombinant murine subunits of the RBP-3 protein were purified and used to immunize C57BL/6J mice to induce EAU. An overlapping peptide library was used to screen RBP-3 subunit 3 for immunogenicity and pathogenicity. Disease phenotype and characterization of pathogenic subunits and peptides was undertaken by topical endoscopic fundal imaging, immunohistochemistry, proliferation assays and flow cytometry. RBP-3 subunits 1, 2 and 3 induced EAU in the C57BL/6J mice, with subunit 3 eliciting the most destructive clinical disease. Within subunit 3 we identified a novel uveitogenic epitope, 629-643. The disease induced by this peptide was comparable to that produced by the uveitogenic 1-20 peptide. Following immunization, peptide-specific responses by CD4(+) and CD8(+) T-cell subsets were detected, and cells from both populations were present in the retinal inflammatory infiltrate. Intramolecular epitope spreading between 629-643 and 1-20 was detected in mice with clinical signs of disease. The 629-643 RBP-3 peptide is a major uveitogenic peptide for the induction of EAU in C57BL/6J mice and the persistent clinical disease induced with one peptide leads to epitope spreading. PMID- 26152847 TI - A highly sensitive, direct and label-free technique for Hg(2+) detection using Kelvin probe force microscopy. AB - For several decades, various nanomaterials have been used in a wide range of industrial fields, research areas, and commercial products. Among many nanomaterials, nano-sized mercury materials are one of the most widely used nanomaterials in real life. However, due to the high toxicity of Hg(2+), it is imperative to develop an effective and practical detection method for Hg(2+) to protect human health and environment. In this study, a highly sensitive, label free method of detecting Hg(2+) that requires only a single drop of solution was developed. The detection mechanism is based on the different surface potential arising from Hg(2+) binding to mismatched thymine-thymine sequences, creating a very stable base pair. The surface potential is measured with Kelvin probe force microscopy (KPFM) to a molecular resolution. The developed method is capable of detecting 2 fmol of Hg(2+), which is 500 times more sensitive than previously reported techniques. Moreover, our method can selectively detect Hg(2+) and can also be applied to tap water and river water. This KPFM-based Hg(2+) detection method can be used as an early detection technique for practical applications. PMID- 26152848 TI - Hand ischemia after transradial coronary angiography: resulting in right ring finger amputation. AB - Critical hand ischemia is an extremely rare and serious complication of transradial coronary angiography. It is almost always associated with radial artery occlusion. Early recognition and involvement of vascular surgery is imperative for optimal management. Up to our knowledge, there have been only 5 cases reported in the medical literature. Herein, we describe a case of an 81 year-old male who had undergone transradial coronary intervention complicated by critical hand ischemia requiring amputation of the right 4th finger. PMID- 26152849 TI - Experts' recommendations for the management of adult patients with cardiogenic shock. AB - Unlike for septic shock, there are no specific international recommendations regarding the management of cardiogenic shock (CS) in critically ill patients. We present herein recommendations for the management of cardiogenic shock in adults, developed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system by an expert group of the French-Language Society of Intensive Care (Societe de Reanimation de Langue Francaise (SRLF)), with the participation the French Society of Anesthesia and Intensive Care (SFAR), the French Cardiology Society (SFC), the French Emergency Medicine Society (SFMU), and the French Society of Thoracic and Cardiovascular Surgery (SFCTCV). The recommendations cover 15 fields of application such as: epidemiology, myocardial infarction, monitoring, vasoactive drugs, prehospital care, cardiac arrest, mechanical assistance, general treatments, cardiac surgery, poisoning, cardiogenic shock complicating end-stage cardiac failure, post-shock treatment, various etiologies, and medical care pathway. The experts highlight the fact that CS is a rare disease, the management of which requires a multidisciplinary technical platform as well as specialized and experienced medical teams. In particular, each expert center must be able to provide, at the same site, skills in a variety of disciplines, including medical and interventional cardiology, anesthesia, thoracic and vascular surgery, intensive care, cardiac assistance, radiology including for interventional vascular procedures, and a circulatory support mobile unit. PMID- 26152850 TI - Copper(I) cysteine complexes: efficient earth-abundant oxidation co-catalysts for visible light-driven photocatalytic H2 production. AB - A copper(i) cysteine complex generated by mixing Cu(ii) ions with cysteine in aqueous solution greatly enhanced the activity of CdSe photocatalysts for H2 production in aqueous solution under visible light excitation. The complex can enhance the H2 evolution rate by as much as 150 times, by acting as an oxidation co-catalyst and increasing charge carrier lifetimes. The copper(i) cysteine complex can also be applied to enhance the H2 production performance of other semiconductor photocatalyst systems, thereby affording a new research direction in the development of co-catalysts for solar hydrogen production. PMID- 26152851 TI - A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG). AB - Primary lymphoma of the lung is a rare entity. Clinical features, optimal treatment, role of surgery and outcomes are not well defined, and the follow-up is variable in published data. Clinical data of 205 patients who were confirmed to have bronchus mucosa-associated lymphoid tissue lymphoma from December 1986 to December 2011 in 17 different centres worldwide were evaluated. Fifty-five per cent of the patients were female. The median age at diagnosis was 62 (range 28 88) years. Only 9% had a history of exposure to toxic substances, while about 45% of the patients had a history of smoking. Ten per cent of the patients had autoimmune disease at presentation, and 19% patients had a reported preexisting lung disease. Treatment modalities included surgery alone in 63 patients (30%), radiotherapy in 3 (2%), antibiotics in 1 (1%) and systemic treatment in 128 (62%). Patients receiving a local approach, mainly surgical resection, experienced significantly improved progression-free survival (p = 0.003) versus those receiving a systemic treatment. There were no other significant differences among treatment modalities. The survival data confirm the indolent nature of the disease. Local therapy (surgery or radiotherapy) results in long-term disease free survival for patients with localized disease. Systemic treatment, including alkylating-containing regimens, can be reserved to patients in relapse after incomplete surgical excision or for patients with advanced disease. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26152852 TI - Trace Element Changes in Thoracic Aortic Dissection. AB - Thoracic aortic dissection is a life-threatening condition with an incompletely understood pathogenesis. Trace elements are essential for the functioning of different processes in the body, including the immune system and associated responses to infection/inflammation. Because inflammation may be part of the pathogenesis of thoracic aortic dissection, we investigated whether trace element changes associated with inflammation occur in serum and tissue samples during the disease. The study included 21 patients undergoing surgery for thoracic aortic dissection, 10 forensic autopsy specimens for tissue controls and 23 healthy blood donors for serum controls. Levels of magnesium (Mg), calcium (Ca), vanadium (V), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd) and mercury (Hg) were measured in the aortic tissue and serum by inductively coupled plasma-mass spectrometry (ICP-MS). In the serum, Ca, V, Cu and Zn decreased, whereas Fe increased. In the tissue, Cu and Zn decreased and Fe tended to increase. The Cu/Zn ratio in the serum, a marker of infection/inflammation, did not change in the patients. Concerning trace element changes in the serum and tissue, our data do not support the hypothesis that inflammation is involved in the pathogenesis of thoracic aortic dissection. PMID- 26152853 TI - Iodine Affects Differentiation and Migration Process in Trophoblastic Cells. AB - Iodine deficiency is associated with oxidative stress increase and preeclampsia during gestation, suggesting that iodine concentration plays an important role in the normal placenta physiology. The question raised is to analyze the effect of iodine deficiency on oxidative stress, viability, differentiation, and migration process and changes in the expression of differentiation and migration markers. Iodine deprivation was done using potassium perchlorate (KCLO4) to block sodium iodide symporter (NIS) transporter and 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid DIDS to inhibit pendrine (PEN) transport for 3-48 h. Then trophoblast cells were treated with low iodine doses of 5-500 MUM and high iodine doses of 100-5000 MUM. Oxidative stress, viability, and human chorionic gonadotropin (hGC) were measured by colorimetric methods. Migration throphoblast cells were evaluated by both wound healing and Boyden chamber assays. Changes in mRNA expression were analyzed by real-time RT-PCR. Iodine deprivation induces a significant increase of reactive oxygen species (ROS), viability, and migration process vs control cells. We found a significant overregulation in the mRNA's peroxisome proliferator-activated receptor (PPAR-gamma), Snail, and matrix metalloproteinase-9 (MMP-9) mRNA's in cells deprived of iodine, as well as a down glial cell missing-1 (GCM-1) regulation, hGC, pregnancy-associated plasma protein A (PAPP-A), and E-cadherin mRNA expression. The expression of hypoxic induction factor alpha (HIFalpha) mRNA does not change with iodine deprivation. In cells deprived of iodine, supplementing low iodine doses (5-500 MUM) does not induce any significant changes in viability. However, ROS and migration process were decreased, although we found an increased human chorionic gonadotropin (hCG) secretion as a differentiation marker. In addition, we found that PPAR-gamma, Snail, and MPP-9 mRNAs expression are downregulated with low iodine doses, in contrast with GCM-1, PAPP-A, hGC, and E-cadherin that increase their expression vs cells deprived of iodine. High iodine doses (1000-5000 MUM) have shown cytotoxic effects. Based on our results, iodine is important for keeping the proliferation/differentiation balance in the placenta. PMID- 26152855 TI - The association between objectively measured physical activity and life-space mobility among older people. AB - The purpose of this cross-sectional study was to investigate the association between objectively measured physical activity and life-space mobility in community-dwelling older people. Life-space refers to the spatial area a person purposefully moves through in daily life (bedroom, home, yard, neighborhood, town, and beyond) and life-space mobility to the frequency of travel and the help needed when moving through different life-space areas. The study population comprised community-living 75- to 90-year-old people {n = 174; median age 79.7 [interquartile range (IQR) 7.1]}, participating in the accelerometer substudy of Life-Space Mobility in Old Age (LISPE) project. Step counts and activity time were measured by an accelerometer (Hookie "AM20 Activity Meter") for 7 days. Life space mobility was assessed with Life-Space Assessment (LSA) questionnaire. Altogether, 16% had a life-space area restricted to the neighborhood when moving independently. Participants with a restricted life space were less physically active and about 70% of them had exceptionally low values in daily step counts (<= 615 steps) and moderate activity time (<= 6.8 min). Higher step counts and activity time correlated positively with life-space mobility. Prospective studies are needed to clarify the temporal order of low physical activity level and restriction in life-space mobility. PMID- 26152856 TI - Climate change impacts on marine water quality: The case study of the Northern Adriatic sea. AB - Climate change is posing additional pressures on coastal ecosystems due to variations in water biogeochemical and physico-chemical parameters (e.g., pH, salinity) leading to aquatic ecosystem degradation. With the main aim of analyzing the potential impacts of climate change on marine water quality, a Regional Risk Assessment methodology was developed and applied to coastal marine waters of the North Adriatic. It integrates the outputs of regional biogeochemical and physico-chemical models considering future climate change scenarios (i.e., years 2070 and 2100) with site-specific environmental and socio economic indicators. Results showed that salinity and temperature will be the main drivers of changes, together with macronutrients, especially in the area of the Po' river delta. The final outputs are exposure, susceptibility and risk maps supporting the communication of the potential consequences of climate change on water quality to decision makers and stakeholders and provide a basis for the definition of adaptation and management strategies. PMID- 26152857 TI - Respiratory syncytial virus infections in pediatric transplant recipients: A Canadian Paediatric Surveillance Program study. AB - The incidence and spectrum of severity of RSV infections in SOT or HSCT recipients is not known. From September 2010 through August 2013, pediatricians were surveyed monthly by the CPSP for SOT or HSCT recipients with RSV infection within two yr post-transplant. There were 24 completed case report forms that fit the inclusion criteria (10 HSCT and 14 SOT recipients). Six of 24 cases (25%) remained outpatients, and 11 (46%) were managed on an inpatient ward, while seven (29%) required intensive care of which five required mechanical ventilation and two died of RSV infection. Ten of 23 cases (43%) were nosocomial with these data not recorded for one case. Many transplant recipients recover uneventfully from RSV infection in the first two yr post-transplant. However, severe disease and death also occur. Larger studies are required to establish risk factors for poor outcomes. Prevention of nosocomial RSV should be a priority in transplant recipients. PMID- 26152858 TI - A diagnostic predicament: activated sarcoidosis or pulmonary histoplasmosis. A case report. AB - We report a case of a 41-year-old man presenting with persisting fevers over 2 weeks. The patient had spent 4 weeks in Central America. He was in control of a stable stage II sarcoidosis. Laboratory and various microbiological tests as well as chest radiography led to no diagnosis. Activated sarcoidosis was hypothesized as the most likely diagnosis. However, we considered an infectious process as a differential diagnosis, in detail, the travel history imposed histoplasmosis. Chest-CT documented localized interstitial consolidations. Bronchoscopy with bronchoalveolar lavage (BAL) and biopsy was performed. Results of BAL fluid, biopsy, distinct sarcoidosis serum markers and a borderline positive histoplasmosis-serology yielded in a diagnostic dilemma as no distinct diagnosis was drawable. After the patient was already started on a prednisolone trial, the final diagnosis - pulmonary histoplasmosis - could be achieved via positive culture and PCR out of the BAL fluid. This case shows the difficult differentiation between an acute exacerbation of a chronic pulmonary disease and a concomitant infection, which was especially aggravated in this case as the histoplasmosis masqueraded an acute picture of sarcoidosis. PMID- 26152859 TI - Differences in spirometry values between U.S. children 6-11 years and adolescents 12-19 years with current asthma, 2007-2010. AB - BACKGROUND: National Asthma Education and Prevention Program (NAEPP) guidelines recommend that periodic spirometry be performed in youth with asthma. NAEPP uses different spirometry criteria to define uncontrolled asthma for children (6-11 years) and adolescents (12+ years). OBJECTIVE: To describe differences in spirometry between U.S. children and adolescents with current asthma. METHODS: We examined cross-sectional spirometry data from 453 U.S. youth with current asthma age 6-19 years from the 2007-2010 National Health and Nutrition Examination Surveys. The main outcomes were percentage predicted forced expiratory volume at 1 sec (FEV1%) <=80 and the ratio of FEV1 to forced vital capacity (FEV1/FVC) <=0.80. We also examined the prevalence of youth with spirometry values consistent with uncontrolled asthma, using NAEPP age-specific criteria, defined for children aged 6-11 years as FEV1% <=80 or FEV1/FVC <=0.80, and for adolescents aged 12-19 years as FEV1% <=80. RESULTS: Children 6-11 years and adolescents 12-19 years did not differ in prevalence of FEV1% <=80 (10.1% vs. 9.0%) or FEV1/FVC <=0.80 (30.6% vs. 29.8%). However, based on the NAEPP age specific criteria, 33.0% of children 6-11 years and 9.0% of adolescents 12-19 years had spirometry values consistent with uncontrolled asthma (P < 0.001). CONCLUSION: Children 6-11 years and adolescents 12-19 years with current asthma did not differ in the percentage with FEV1% <=80 or FEV1/FVC <=0.80. However, the percent of children and adolescents with spirometry values consistent with uncontrolled asthma did differ. The difference appears to stem mainly from the different spirometry criteria for the two age groups. PMID- 26152860 TI - In response to Palatal myoclonus: Algorithm for management with botulinum toxin based on clinical disease characteristics. PMID- 26152867 TI - Factors important in laryngology fellow and laryngology fellowship selection. AB - OBJECTIVES/HYPOTHESIS: To determine factors that laryngology fellowship directors believe are most important in choosing a fellow and that laryngology applicants believe are most important in choosing a program. The number of laryngology fellowship programs and the number of laryngology fellowship applicants have been increasing in recent years. Selection criteria in choosing a fellow or fellowship program have not been studied. METHODS: Survey study using anonymous online questionnaires of laryngology fellowship directors and recent laryngology fellowship applicants. Directors were asked to rate qualities for judging the strength of a fellowship applicant. Applicants were assessed for the importance of various factors in choosing a fellowship. RESULTS: Sixteen of 27 fellowship directors (59%) and 33 of 53 fellowship applicants (62%) contacted responded to the survey. Program directors listed interview performance, letters of recommendation, and personal knowledge of applicant as the most important factors. Gender or ethnicity, previous research in laryngology, and likelihood that the applicant will rank the director's program highly were ranked as least important factors. Applicants ranked personal rapport with fellowship mentor(s), large experience in endoscopic surgeries, and reputation of mentor(s) as most important, whereas call schedule, salary, and having more than one fellow per year were ranked as least important factors. CONCLUSION: Interview performance, trusted colleague's recommendation, and personal knowledge were ranked as the most important factors in fellow selection. These criteria are consistent with previous research on otolaryngology residency and pediatric otolaryngology fellow selection. When selecting a fellowship, laryngology fellowship applicants choose based on personal rapport with mentor, opportunity to learn endoscopic surgeries, and mentor reputation. LEVEL OF EVIDENCE: N/A. PMID- 26152864 TI - Is birth a critical period in the pathogenesis of autism spectrum disorders? AB - Birth is associated with a neuroprotective, oxytocin-mediated abrupt excitatory to-inhibitory GABA shift that is abolished in autism, and its restoration attenuates the disorder in offspring. In this Opinion article, I discuss the links between birth-related stressful mechanisms, persistent excitatory GABA actions, perturbed network oscillations and autism. I propose that birth (parturition) is a critical period that confirms, attenuates or aggravates the deleterious effects of intrauterine genetic or environmental insults. PMID- 26152868 TI - Monochromatic image reconstruction by dual energy imaging allows half iodine load computed tomography coronary angiography. AB - PURPOSE: To compare image interpretability and diagnostic performance of dual energy CT coronary angiography (DE-CTCA) performed with 50% iodine load reduction versus single energy acquisitions (SE-CTCA) with full iodine load. MATERIALS AND METHODS: The present prospective study involved patients with suspected coronary artery disease (CAD) clinically referred for CTCA. DE-CTCA with 50% iodine volume load was performed first, and after heart rate returned to baseline SE-CTCA was performed using full iodine volume load. The primary endpoint was to compare image interpretability between groups. DE-CTCA was performed by rapid switching between low and high tube potentials (80-140 kV) from a single source, allowing the generation of monochromatic image reconstructions ranging from 40 to 140 keV. Image quality assessment was performed using a 5-point Likert scale. RESULTS: Thirty-six patients constituted the study population. The mean heart rate before the CT scan (DE-CTCA 57.3 +/- 10.7 bpm vs. SE-CTCA 58.5 +/- 11.2 bpm, p=0.29) and the mean effective radiation dose (3.5 +/- 1.9 mSv vs. 3.8 +/- 0.9 mSv, p=0.48) did not differ between groups. Likert image quality scores were similar between groups (DE-CTCA 4.42 +/- 0.98 vs. SE-CTCA 4.43 +/- 0.84, p=0.67). Signal-to-noise and contrast-to-noise ratios were significantly lower with DE-CTCA, driven by lower signal density levels at 60 keV compared to SE-CTCA. The sensitivity and specificity for the detection of stenosis >50% was indistinguishable between groups (DE-CTCA 84.4% (69.9-93.0%), 87.1% (81.6-91.2%); SE-CTCA 84.4% (69.9 93.0%), 87.1% (81.6-91.2%). CONCLUSIONS: In this pilot, prospective study, dual energy CTCA imaging with half iodine load achieved comparable interpretability than full iodine load with single energy CTCA. PMID- 26152869 TI - From 3D to 4D: Integration of temporal information into CT angiography studies. AB - CT angiography is the current clinical standard for the imaging many vascular illnesses. This is traditionally done with a single arterial contrast phase. However, advances in CT technology allow for a dynamic acquisition of the contrast bolus, thus adding temporal information to the examination. The aim of this article is to highlight the clinical possibilities of dynamic CTA using 2 examples. The accuracy of the detection and quantification of stenosis in patients with peripheral arterial occlusive disease, especially in stadium III and IV, is significantly improved when performing dynamic CTA examinations. The post-interventional follow-up of examinations of EVAR benefit from dynamic information, allowing for a higher sensitivity and specificity, as well as allowing more accurate classification of potential endoleaks. The described radiation dose for these dynamic examinations is low, but this can be further optimized by using lower tube voltages. There are a multitude of applications for dynamic CTA that need to be further explored in future studies. PMID- 26152870 TI - Clinical value of 68Ga-DOTATATE-PET/CT compared to stand-alone contrast enhanced CT for the detection of extra-hepatic metastases in patients with neuroendocrine tumours (NET). AB - PURPOSE: To compare and outline the beneficial skills of combined (68)Ga-DOTATATE positron emission tomography (PET) with concurrent contrast enhanced X-ray computed tomography (ceCT) against stand-alone ceCT in 54 patients with neuroendocrine tumours (NET). METHODS: Patients with histologically confirmed NET and available follow-up of at least 6 months (median 12.6 months; range 6.1-23.2) were included. PET/CT and ceCT images were initially analyzed separately by two blinded nuclear medicine physicians and two radiologists, respectively. In a second step all four physicians reviewed all detected lesions together reaching a consensus-grading for PET/ceCT. The results were then compared to the reference standard consisting of clinical follow-up data. RESULTS: With regard to true positive lesions, PET/ceCT vs. stand alone ceCT detected 139 vs. 48 bone-lesions, 106 vs. 71 lymph node metastases and 26 vs. 26 pulmonary lesions. On a per patient basis, PET/ceCT achieved a higher sensitivity (100% vs. 47%) and specificity (89% vs. 49%) for bone lesions than ceCT. For lymph nodes the effect was similar (sensitivity 92% vs. 64% and specificity 83% vs. 59%). For the detection of pulmonary lesions the sensitivity was identical (100%) while specificity of PET/ceCT was superior to ceCT-alone (95% vs. 82%). CONCLUSION: In summary, the use of (68)Ga-DOTATATE PET/ceCT leads to an increase in sensitivity and specificity in the detection of extra-hepatic NET metastases compared to stand-alone ceCT. Therefore, (68)Ga-DOTATATE PET/ceCT should be the imaging modality of choice in patients with NET. PMID- 26152871 TI - [Statement on the elimination of the Max Burger Prize of the German Society of Gerontology and Geriatrics]. PMID- 26152865 TI - From the neuron doctrine to neural networks. AB - For over a century, the neuron doctrine--which states that the neuron is the structural and functional unit of the nervous system--has provided a conceptual foundation for neuroscience. This viewpoint reflects its origins in a time when the use of single-neuron anatomical and physiological techniques was prominent. However, newer multineuronal recording methods have revealed that ensembles of neurons, rather than individual cells, can form physiological units and generate emergent functional properties and states. As a new paradigm for neuroscience, neural network models have the potential to incorporate knowledge acquired with single-neuron approaches to help us understand how emergent functional states generate behaviour, cognition and mental disease. PMID- 26152872 TI - [Analgesics in geriatric patients. Adverse side effects and interactions]. AB - Pain is a widespread symptom in clinical practice. Older adults and chronically ill patients are particularly affected. In multimorbid geriatric patients, pharmacological pain treatment is an extension of a previously existing multimedication. Besides the efficacy of pain treatment, drug side effects and drug-drug interactions have to be taken into account to minimize the health risk for these patients. Apart from the number of prescriptions, the age-related pharmacokinetic and pharmacodynamic changes significantly increase the risk among older adults. The use of non-steroidal anti-inflammatory drugs (NSAID) is widespread but NSAIDs have the highest risk of adverse drug reactions and drug interactions. In particular, the gastrointestinal, cardiovascular, renal and coagulation systems are affected. Apart from the known toxic effect on the liver (in high doses), paracetamol (acetaminophen) has similar risks although to a lesser degree. According to current data, metamizol is actually better than its reputation suggests. The risk of potential drug interactions seems to be low. Apart from the risk of sedation in combination with other drugs, tramadol and other opioids can induce the serotonin syndrome. Among older adults, especially in the case of polypharmacy, an individualized approach should be considered instead of sticking to the pain management recommended by the World Health Organization (WHO) in order to minimize drug-drug interactions and adverse drug reactions. PMID- 26152873 TI - Role of a Limited Transarticular Release in Severe Hallux Valgus Correction. AB - BACKGROUND: Hallux valgus (HV) treatment is continuously evolving, and no definitive treatment can be recommended. Osteotomies are the main surgical choice for these deformities, but no clear role for soft tissue procedures is available. OBJECTIVE: To perform a retrospective comparison of the radiographic and clinical outcomes of 2 groups of patients with severe HV operated with the same osteotomy technique but differing on the type of lateral release. METHODS: Two groups of patients with symptomatic moderate to severe HV deformities were operated with the same proximal metatarsal osteotomy, which differed on the type of lateral release: group 1 had limited transarticular lateral capsule release (n = 62), and group 2 complete lateral release, including capsule, adductor tendon, and intermetatarsal (IM) ligament (n = 57). We recorded the American Orthopaedic Foot & Ankle Society (AOFAS) score, HV and IM angles, first metatarsal shortening, concomitant metatarsal shortening osteotomies (Weil), Akin osteotomies, and complications. RESULTS: The postoperative AOFAS score in group 1 was similar to that of group 2. The HV and IM angles improved in both groups with no significant difference. The multivariate analysis showed no influence of any variable analyzed on HV or IM angle improvement. Regarding AOFAS score improvement, a limited lateral release was associated with a higher increase in AOFAS score (P = .019). CONCLUSION: No studies are available to identify which soft tissue structures are involved in HV deformities nor which have to be released, if any. A limited transarticular release can provide similar clinical and radiologic outcomes when compared with a classic open lateral release. LEVEL OF EVIDENCE: Level IV, case series. PMID- 26152874 TI - Existing drugs and their application in drug discovery targeting cancer stem cells. AB - Despite standard cancer therapies such as chemotherapy and targeted therapy have shown some efficacies, the cancer in many cases eventually relapses and metastasizes upon stopping the treatment. There is a small subpopulation of cancer cells within tumor, with specific characters similar to those found in stem cells. This group of cancer cells is known as tumor-initiating or cancer stem cells (CSCs), which have an ability to self-renew and give rise to cancer cell progeny. CSCs are related with drug resistance, metastasis and relapse of cancer, hence emerging as a crucial drug target for eliminating cancer. Rapid advancement of CSC biology has enabled researchers to isolate and culture CSCs in vitro, making the cells amenable to high-throughput drug screening. Recently, drug repositioning, which utilizes existing drugs to develop potential new indications, has been gaining popularity as an alternative approach for the drug discovery. As existing drugs have favorable bioavailability and safety profiles, drug repositioning is now actively exploited for prompt development of therapeutics for many serious diseases, such as cancer. In this review, we will introduce latest examples of attempted drug repositioning targeting CSCs and discuss potential use of the repositioned drugs for cancer therapy. PMID- 26152875 TI - Anti-diabetic and anti-Alzheimer's disease activities of Angelica decursiva. AB - Diabetes mellitus (DM) and Alzheimer's disease (AD) constitute two global health issues. DM is an ever-increasing epidemic affecting millions of elderly people worldwide, causing major repercussions on patients' daily lives, mostly due to chronic complications. Complications from DM can affect the brain, thereby characterizing DM as a risk factor for AD. In the present study, we examined the inhibitory activity of methanol extracts of different parts of 12 Angelica species against alpha-glucosidase, protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). The methanol extract of Angelica decursiva exhibited the highest inhibitory activities against alpha-glucosidase, PTP1B, AChE, and BChE and so was selected for further investigation. Repeated column chromatography based on bioactivity-guided fractionation yielded seven compounds (1-7). Among these compounds, nodakenin (1), nodakenetin (2), umbelliferone (3), cis-3'-acetyl-4'-angeloylkhellactone (4), 3'(R)-O-acetyl-4'(S)-O-tigloylkhellactone (5), isorutarine (6), and para hydroxybenzoic acid (7) exhibited potent inhibitory activities against alpha glucosidase, PTP1B, rat lens aldose reductase (RLAR), AChE, BChE, and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). Our results clearly indicate the potential inhibition of alpha-glucosidase, PTP1B, RLAR, AChE, BChE, and BACE1 by A. decursiva as well as its isolated constituents, which could be further explored to develop therapeutic modalities for the treatment of DM and AD. PMID- 26152876 TI - Preparation and performance evaluation of emulsomes as a drug delivery system for silybin. AB - We developed silybin (SIL) emulsomes and evaluated their physicochemical properties and the in vivo pharmacokinetics of SIL delivered by emulsomes in rats. SIL emulsomes were prepared using the thin film dispersion method. SIL emulsomes were evaluated for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release, and in vivo drug delivery in rats. The entrapment efficiency was above 80 %. The average particle size and zeta potential were 364.1 +/- 20 nm and -34 +/- 8 mV, respectively. Morphological analysis revealed that the SIL emulsomes were spherical in shape. Compared to an SIL solution, emulsomes produced sustained release of SIL for up to 48 h after an initial burst release in vitro. The pharmacokinetics of SIL emulsomes in rats were evaluated after intravenous injection, and the results were compared with those obtained for the control SIL solution. Following SIL delivery by emulsomes, the area under the curve was 2.2-fold higher and the mean residence time was 2.5 fold higher than the corresponding values recorded using SIL solution. Hence, emulsomes might represent a promising system for improving the bioavailability of lipophilic drugs. Moreover, emulsomes produce sustained drug release, which is advantageous in the clinical setting. PMID- 26152877 TI - Tuning the emission of aqueous Cu:ZnSe quantum dots to yellow light window. AB - Synthesis of internally doped Cu:ZnSe QDs in an aqueous solution still suffers from narrow tunable emissions from the blue to green light window. In this work, we extended the emission window of aqueous Cu:ZnSe QDs to the yellow light window. Our results show that high solution pH, multiple injections of Zn precursors, and nucleation doping strategy are three key factors for preparing yellow emitted Cu:ZnSe QDs. All these factors can depress the reactivity of CuSe nuclei and Zn monomers, promoting ZnSe growth outside CuSe nuclei rather than form ZnSe nuclei separately. With increased ZnSe QD size, the conduction band and nearby trap state energy levels shift to higher energy sites, causing Cu:ZnSe QDs to have a much longer emission. PMID- 26152878 TI - Scaffold electrodes based on thioctic acid-capped gold nanoparticles coordinated Alcohol Dehydrogenase and Azure A films for high performance biosensor. AB - Nanometric size gold nanoparticles capped with thiotic acid are used to coordinate with the Zn (II) present in the catalytic center of Alcohol Dehydrogenase (ADH). In combination with the NADH oxidation molecular catalyst Azure A, electrografted onto carbon screen-printed electrodes, they are used as scaffold electrodes for the construction of a very efficient ethanol biosensor. The final biosensing device exhibits a highly efficient ethanol oxidation with low overpotential of -0.25 V besides a very good analytical performance with a detection limit of 0.14+/-0.01 MUM and a stable response for more than one month. PMID- 26152879 TI - Prospective glioma grading using single-dose dynamic contrast-enhanced perfusion MRI. AB - AIM: To evaluate the sensitivity and specificity of single-dose dynamic contrast enhanced (DCE) perfusion magnetic resonance imaging (MRI) in prospective evaluation of glioma grading and to correlate the relative cerebral blood volume (rCBV) values with mitotic and ki-67 indexes obtained at histopathology. MATERIALS AND METHODS: A total of 53 histologically proven patients with glioma were included in this study. DCE-MRI perfusion with a single dose of contrast medium was included in brain tumour protocol and prospective grading of glioma into low and high grade was done based on a previously reported rCBV cut-off value of 3. Tumours with rCBV >= 3 were considered to be high grade and rCBV < 3 were considered to be low grade. The sensitivity and specificity of the cut-off value were estimated. Ki-67 and mitotic indexes were also obtained on histopathological analysis along with histological grading. RESULTS: Based on pre defined rCBV cut-off values, prospective grading of low- and high-grade glioma was achieved with a sensitivity and specificity of 97.22% and 100%, respectively. Significant correlation was found between the mitotic/ki-67 indexes and rCBV values when data for high- and low-grade tumours was combined. CONCLUSION: DCE MRI performed with a single dose of contrast medium is as effective as a protocol with a double-dose of contrast medium for glioma grading using 3 T MRI and could be added to the routine evaluation protocol of brain tumours. PMID- 26152880 TI - Implementation of a split-bolus single-pass CT protocol at a UK major trauma centre to reduce excess radiation dose in trauma pan-CT. AB - AIM: To quantify the dose reduction and ensure that the use of a split-bolus protocol provided sufficient vascular enhancement. MATERIALS AND METHODS: Between 1 January 2014 and 31 May 2014, both split bolus and traditional two-phase scans were performed on a single CT scanner (SOMATOM Definition AS+, Siemens Healthcare) using a two-pump injector (Medrad Stellant). Both protocols used Siemens' proprietary tube current and tube voltage modulation techniques (CARE dose and CARE kV). The protocols were compared retrospectively to assess the dose length product (DLP), aortic radiodensity at the level of the coeliac axis and radiodensity of the portal vein. RESULTS: There were 151 trauma CT examinations during this period. Seventy-eight used the split-bolus protocol. Seventy-one had traditional two-phase imaging. One patient was excluded as they were under the age of 18 years. The radiodensity measurements for the portal vein were significantly higher (p<0.001) in the split-bolus protocol. The mean aortic enhancement in both protocols exceeded 250 HU, although the traditional two-phase protocol gave greater arterial enhancement (p<0.001) than the split-bolus protocol. The split-bolus protocol had a significantly lower (p<0.001) DLP with 43.5% reduction in the mean DLP compared to the traditional protocol. CONCLUSION: Split-bolus CT imaging offers significant dose reduction for this relatively young population while retaining both arterial and venous enhancement. PMID- 26152881 TI - Nanoscale Kirkendall growth of silicalite-1 zeolite mesocrystals with controlled mesoporosity and size. AB - The Kirkendall effect was utilized to synthesize mesoporous silicalite-1 zeolite nanocrystals without the involvement of additional templates. The mesopore size as well as the particle size can be easily controlled by nanoscale Kirkendall growth via significantly reducing the amount of water or tetrapropylammonium hydroxide, which were used in large quantities in conventional methods. The Kirkendall growth method is thus suitable for large-scale synthesis of mesoporous MFI zeolites with very high yields but low cost for practical applications. PMID- 26152883 TI - The Grieving Process: A Necessary Step Toward Healing. PMID- 26152884 TI - Hands-free vein visualizer for preoperative assessment of recipient veins. PMID- 26152882 TI - The Impact of Chronic Early Administration of Psychostimulants on Brain Expression of BDNF and Other Neuroplasticity-Relevant Proteins. AB - ABSRACT: Frequently, healthy individuals, children, and students are using stimulants to treat attention deficit hyperactivity disorder (ADHD)-like symptoms or to enhance cognitive capacity, attention and concentration. Methylphenidate, the most common treatment for ADHD, similarly to cocaine, blocks the dopamine reuptake, leading to increase in dopamine level in the synaptic cleft. Brain derived neurotrophic factor (BDNF) and other neuroplasticity-relevant proteins have a major role in cellular plasticity during development and maturation of the brain. Young Sprague Dawley rats (postnatal days (PND) 14) were treated chronically with either cocaine or methylphenidate. The rats were examined behaviorally and biochemically at several time points (PND 35, 56, 70, and 90). We found age-dependent, but stimulant-independent, alterations in the mRNA expression levels of microtubule-associated protein tau, doublecortin, and synaptophysin. The PND 90 rats, treated with methylphenidate at an early age, exhibited increased BDNF protein levels in the prefrontal cortex compared to the saline-treated group. Despite the treatment effects at the biochemical level, cocaine and methylphenidate treatments at an early age had only minor effects on the behavioral parameters measured at older ages. The biochemical alterations may reflect neuroprotective or neuroplastic effects of chronic methylphenidate treatment at an early age. PMID- 26152885 TI - A Dilemma in the Glycosaminoglycan-Based Therapy: Synthetic or Naturally Unique Molecules? AB - Glycosaminoglycans (GAGs) are widely explored in the biomedical market as functional ingredients in pharmaceutical or nutraceutical preparations. This extensive application of GAGs is justified by their multiple activities across several systems including, but not limited to, coagulation, thrombosis, inflammation, cancer, angiogenesis, cell differentiation, tissue repair, and microbial infections. Therapeutic GAGs are commonly extracted from mammalian tissues. Although functional in diverse systems, mammalian GAGs present serious downsides in therapy such as contamination risk from the mammalian tissues. In order to overcome some of the downsides, two new GAG sources have been appearing as alternatives to the mammalian-derived molecules. They are the synthetic GAGs and those extracted from nonmammalian origins such as invertebrate animals. This report overviews the general aspects of each GAG alternative and compares critically their pros and cons attributes in light of the prospects for the future of GAG-based therapy. PMID- 26152886 TI - Impact of the radius of the injector system on the cell viability in descemet membrane endothelial keratoplasty: an ex vivo experimental study. AB - PURPOSE: To evaluate the impact of the radius of the injector system on the viability of the endothelial cells in Descemet membrane endothelial keratoplasty (DMEK). METHODS: Descemet membranes (DMs) of 30 corneoscleral rims were used in a paired design and divided into three groups (A, B, C). The right corneas were used as control (without shooting through the injector after DM preparation) and the left cornea for simulation of the implantation step (shooting through a glass injector of different radii). The injector in Group A had a diameter of 0.5 mm, group B 0.9 mm and group C 1.4 mm. Prior to preparation, endothelial cell count was measured and endothelial cell quality assessed. Quantification of potential damage was achieved by staining with a viability bioassay (calcein acetoxymethyl and ethidium homodimer-1) and DAPI. Apoptosis was evaluated by TUNEL (terminal dUTP nick-end labelling) staining. RESULTS: The average percentage of the endothelial cell death ratios was 4.9 +/- 3.3% in group A (n = 5), 3.7 +/- 3.7% in group B (n = 5) and 3.9 +/- 3.6% in group C (n = 5) with no significant difference compared to the control. The average percentage of apoptotic endothelial cells was 0.05 +/- 0.05%, 0.60 +/- 0.53% and 0.15 +/- 0.26% in groups A, B and C, respectively, with no significant difference compared to the control. CONCLUSIONS: Prepared grafts for transplantation in DMEK procedures may be injected through a smaller sized injector system of up to 0.5 mm with no significant increase in cell loss. Clinical studies are necessary to draw a final conclusion. PMID- 26152887 TI - Ultrasound triggered drug delivery with liposomal nested microbubbles. AB - When ultrasound contrast agent microbubbles are nested within a liposome, damage to the liposome membrane caused by both stable and inertial cavitation of the microbubble allows for release of the aqueous core of the liposome. Triggered release was not accomplished unless microbubbles were present within the liposome. Leakage was tested using fluorescence assays developed specifically for this drug delivery vehicle and qualitative measurements using an optical microscope. These studies were done using a 1 MHz focused ultrasound transducer while varying parameters including peak negative ultrasound pressure, average liposome diameter, and microbubble concentration. Two regimes exist for membrane disruption caused by cavitating microbubbles. A faster release rate, as well as permanent membrane damage are seen for samples exposed to high pressure (2.1-3.7 MPa). A slower release rate and dilation/temporary poration are characteristic of stable cavitation for low pressure studies (0.54-1.7 MPa). PMID- 26152888 TI - Improved False Discovery Rate Estimation Procedure for Shotgun Proteomics. AB - Interpreting the potentially vast number of hypotheses generated by a shotgun proteomics experiment requires a valid and accurate procedure for assigning statistical confidence estimates to identified tandem mass spectra. Despite the crucial role such procedures play in most high-throughput proteomics experiments, the scientific literature has not reached a consensus about the best confidence estimation methodology. In this work, we evaluate, using theoretical and empirical analysis, four previously proposed protocols for estimating the false discovery rate (FDR) associated with a set of identified tandem mass spectra: two variants of the target-decoy competition protocol (TDC) of Elias and Gygi and two variants of the separate target-decoy search protocol of Kall et al. Our analysis reveals significant biases in the two separate target-decoy search protocols. Moreover, the one TDC protocol that provides an unbiased FDR estimate among the target PSMs does so at the cost of forfeiting a random subset of high-scoring spectrum identifications. We therefore propose the mix-max procedure to provide unbiased, accurate FDR estimates in the presence of well-calibrated scores. The method avoids biases associated with the two separate target-decoy search protocols and also avoids the propensity for target-decoy competition to discard a random subset of high-scoring target identifications. PMID- 26152889 TI - Gestational Age at First Antenatal Care Visit in Malawi. AB - OBJECTIVES: This paper examines the gestational age at first antenatal care (ANC) visit and factors associated with timely initiation of ANC in Malawi in a context where maternal and child health services are generally provided for free. METHODS: Lognormal survival models are applied to Demographic and Health Survey data from a nationally representative sample of women (n = 13,588) of child bearing age. RESULTS: The findings of this study show that less than 30 % of pregnant women initiate ANC within the World Health Organization recommended gestational timeframe of 16 weeks or earlier. The hazard analysis shows a gradient in the initiation of ANC by maternal education level, with least educated mothers most likely to delay their first ANC visit. However, after adjusting for variables capturing intimate partner violence in the multivariate models, the effect of maternal education attenuated and lost statistical significance. Other significant predictors of gestational age at first ANC include media exposure, perceived distance from health facility, age, and birth order. CONCLUSIONS FOR PRACTICE: The findings of the study link domestic violence directly with the gestational age at which mothers initiate ANC, suggesting that gender-based violence may operate through delayed initiation of ANC to undermine maternal and child health outcomes. PMID- 26152891 TI - Social Work Services Utilization by Children with Medical Complexity. AB - OBJECTIVES: Children with medical complexity (CMC) are a growing population in pediatric primary care practices, and families caring for these children face increased medical, developmental, education and social needs. The objective of this study was to quantify hospital-wide social work services utilization by CMC compared to non-medically-complex children (non-CMC) to inform the development of family-centered care models that support these vulnerable patients and families. METHODS: Social work department records from a tertiary children's hospital were used to compare CMC aged 0-17 (n = 564) with age- and sex-matched non-CMC (n = 1128) over a 16-month retrospective period. The main outcomes measures were the proportion of patients who used social work services and mean number of hours of services provided per patient, both by social work providers in the primary care setting and throughout the hospital. RESULTS: A greater percentage of CMC used social work services than non-CMC (60.3 vs. 18.9%), and CMC used more hours per child (5.50 h/child vs. 0.69). In multivariate analysis, medical complexity was associated with 6.23-fold greater odds of using social work services (95% CI 4.94 7.85) and with 8.07 times more hours of services per child (95% CI 6.30-10.34), independent of primary health insurance, age, or sex. CONCLUSION: This study confirms that CMC use significantly more social work services in the medical setting. This must be considered when designing proactive medical home models to provide high quality family-centered care for this population, and further research is needed to elucidate the factors that drive this utilization. PMID- 26152890 TI - Psychosocial Stress During First Pregnancy Predicts Infant Health Outcomes in the First Postnatal Year. AB - OBJECTIVES: To evaluate the impact of psychosocial stress during pregnancy on infant health outcomes in the first postnatal year. METHODS: A sample of 3000 women completed a stress inventory (the Psychosocial Hassles Scale) during their third trimester before first childbirth. Infant health outcomes were measured via maternal report at 1, 6 and 12 months postpartum. Poisson regression was used to model the effect of maternal stress during pregnancy on infant health outcomes in the first year, controlling for age, race/ethnicity, education, insurance coverage, marital status, and cigarette smoking during pregnancy. RESULTS: Women who were younger, minority, unmarried, publicly insured and without a college degree were more likely to report high levels of prenatal stress. High prenatal stress was a significant predictor of maternal reporting of gastrointestinal illness (p < 0.0001), respiratory illness (p = 0.025), and total illness in the first year (p < 0.0001). High prenatal stress was also a significant predictor of urgent care visits (p < 0.0001) and emergency department visits (p = 0.001). It was not a significant predictor of hospitalizations (p = 0.36). CONCLUSIONS: Maternal prenatal stress is associated with increased maternal reporting of infant illness, as well as increased frequency of both urgent care visits and emergency department visits. PMID- 26152892 TI - Late tracheotomy is associated with higher morbidity and mortality in mechanically ventilated patients. AB - OBJECTIVES/HYPOTHESIS: To determine whether the timing of tracheotomy placement impacts ventilation weaning status and mortality. STUDY DESIGN: Multi-institution retrospective cohort study. METHODS: Demographic data, procedural details, and clinical outcomes were recorded for patients undergoing tracheotomy for prolonged mechanical ventilation across eight sites. The study group was divided into two groups: those undergoing tracheotomy within 14 days of initiation of mechanical ventilation and those undergoing tracheotomy at or after 14 days. Groups were compared for primary outcome measures of mortality and ability to wean from mechanical ventilation within the study period. RESULTS: Of the 539 patients intubated for ventilator dependence with complete data available, 280 (51.9%) underwent tracheotomy within 14 days. Patients who underwent late tracheotomy were 1.72 times more likely to remain ventilator dependent during the follow-up period (95% confidence interval [CI]: 1.12-2.66), and had a 40% increased risk of death (odds ratio: 1.4, 95% CI: 0.96-1.99). CONCLUSIONS: In this multicenter retrospective review of tracheotomy outcomes, late tracheotomy placement (>14 days) was associated with increased mortality and prolonged ventilator dependence. Standardized multidisciplinary management protocols for prolonged mechanical ventilation are recommended, and future work should confirm these results in a prospective manner. LEVEL OF EVIDENCE: 4. PMID- 26152893 TI - Speech-language pathology care and short- and long-term outcomes of laryngeal cancer treatment in the elderly. AB - OBJECTIVES/HYPOTHESIS: To examine associations between speech-language pathology (SLP) care and pretreatment variables, swallowing and airway impairment, and survival in elderly patients treated for laryngeal cancer. STUDY DESIGN: Retrospective analysis of surveillance, epidemiology, and end results (SEER) Medicare data. METHODS: We evaluated longitudinal data from 2,370 patients diagnosed with laryngeal cancer from 2004 to 2007 using cross-tabulations, multivariate logistic regression, and survival analysis. RESULTS: Initial treatment with total laryngectomy (odds ratio [OR] = 3.3 [1.6-6.8]), and dysphagia during treatment (OR = 4.0 [2.2-7.2]) were the only significant predictors of SLP care during the initial treatment period. Speech-language pathology care was more likely during the first year (OR = 4.1 [2.7-6.0]) and second year (OR = 1.6 [1.1-2.3]) following initial treatment; however, only 23.7% of patients ever received SLP care. Pretreatment tracheostomy tube placement (OR = 2.8 [1.1-7.0]), initial treatment with total laryngectomy (OR = 3.4 [2.0-5.6]), dysphagia (OR = 7.6 [5.5-10.4]), stricture (OR = 1.9 [1.1-3.1]), interval tracheostomy tube placement (OR = 3.5 [2.4-5.2]), and salvage surgery (OR = 3.1 [1.6-5.8]) were significantly associated with long-term SLP care. After controlling for relevant variables, SLP care was associated with significant relative attenuation of the OR for dysphagia (50%), stricture (26%), weight loss (20%), and pneumonia (21%). Hazards ratio for death, if under SLP care, was 0.83 (0.70-0.99). CONCLUSION: SLP care is underutilized in elderly laryngeal cancer patients and is largely reserved for select patients in anticipation of total laryngectomy or after the onset of impaired airway and swallowing function, but is associated with improved outcomes. These data suggest a need for treatment guidelines that incorporate the routine use of SLP care during the initial treatment period and beyond. LEVEL OF EVIDENCE: 2c. PMID- 26152894 TI - Partition of genetic trends by origin in Landrace and Large-White pigs. AB - The objective of this study was to analyse the effectiveness of genetic improvement via domestic selection and import for backfat thickness and time on test in a conventional pig breeding programme for Landrace (L) and Large-White (LW) breeds. Phenotype data was available for 25 553 L and 10 432 LW pigs born between 2002 and 2012 from four large-scale farms and 72 family farms. Pedigree information indicated whether each animal was born and registered within the domestic breeding programme or has been imported. This information was used for defining the genetic groups of unknown parents in a pedigree and the partitioning analysis. Breeding values were estimated using a Bayesian analysis of an animal model with and without genetic groups. Such analysis enabled full Bayesian inference of the genetic trends and their partitioning by the origin of germplasm. Estimates of genetic group indicated that imported germplasm was overall better than domestic and substantial changes in estimates of breeding values was observed when genetic group were fitted. The estimated genetic trends in L were favourable and significantly different from zero by the end of the analysed period. Overall, the genetic trends in LW were not different from zero. The relative contribution of imported germplasm to genetic trends was large, especially towards the end of analysed period with 78% and 67% in L and from 50% to 67% in LW. The analyses suggest that domestic breeding activities and sources of imported animals need to be re-evaluated, in particular in LW breed. PMID- 26152895 TI - High-Performance Stable Field Emission with Ultralow Turn on Voltage from rGO Conformal Coated TiO2 Nanotubes 3D Arrays. AB - A facile method to produce conformal coated reduced graphene oxide (rGO) on vertically aligned titanium oxide (TiO2) nanotubes three dimensional (3D) arrays (NTAs) is demonstrated for enhanced field emission display applications. These engineered nano arrays exhibit efficient electron field emission properties such as high field emission current density (80 mA/cm(2)), low turn-on field (1.0 V/MUm) and field enhancement factor (6000) with high emission current stability. Moreover, these enhancements observed in nano arrays attribute to the contribution of low work function with non-rectifying barriers, which allow an easy injection of electrons from the conduction band of TiO2 into the Fermi level of reduced graphene oxide under external electric field. The obtained results are extremely advantageous for its potential application in field emission devices. PMID- 26152896 TI - Percutaneous implantation of (125)iodine seeds for treatment of portal vein tumor thrombosis in hepatocellular carcinoma. AB - The aim of the study is to evaluate the practicability and therapeutic efficacy of (125)iodine seeds implantation percutaneously for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Nineteen patients with HCC accompanied with PVTT received ultrasound-guided implantation of 8-30 (125)iodine seeds, 8 mm apart within the portal vein tumor thrombi. The patients were followed up postoperatively for a period of 3-22 months. The successful rates of the procedure, postoperative changes of liver and renal function, hemogram, complications and therapeutic response were monitored. (125)I seeds were successfully implanted in the portal veins in all patients without serious complications. During the follow-up period, the portal vein tumor thrombi all shrunk obviously. Percutaneous implantation of (125)iodine seeds into the portal vein is an effective and safe treatment for PVTT accompanying HCC. PMID- 26152897 TI - The metaphysical lessons of synthetic biology and neuroscience. AB - In this paper, I examine some important metaphysical lessons that are often presented as derived from two new scientific disciplines: synthetic biology and neuroscience. I analyse four of them: the nature of life, the existence of a soul (the mind-body problem), personhood, and free will. Many caveats are in order, and each 'advance' or each case should be assessed for itself. I conclude that a main lesson can nevertheless be learned: in conjunction with modern science, neuroscience and synthetic biology allow us to enrich old metaphysical debates, to deepen and even renew them. In particular, it becomes less and less plausible to consider life, mind, person, and agency as non-natural or non-physical entities. PMID- 26152898 TI - A recyclable CO surrogate in regioselective alkoxycarbonylation of alkenes: indirect use of carbon dioxide. AB - Herein, we report a Pd-catalysed alkoxycarbonylation of alkenes based on the use of a recyclable CO2 reduction product, the crystalline and air-stable N formylsaccharin, as a CO surrogate. The carbonylation proceeds under ambient conditions in an exceptionally complementary regioselective fashion yielding the desired branched products from styrene derivatives and valuable linear esters from alkyl-substituted alkenes. PMID- 26152899 TI - Production of pristine, sulfur-coated and silicon-alloyed germanium nanoparticles via laser pyrolysis. AB - Here we demonstrate production of three types of germanium containing nanoparticles (NPs) by laser pyrolysis of GeH4 and characterize their sizes, structures and composition. Pristine Ge NPs were fabricated with 50 standard cubic centimeter per minute (sccm) of GeH4 and 25 sccm of SF6 as a photosensitizer gas, while sulfur-coated Ge NPs were produced with 25 sccm of GeH4 and 50 sccm of SF6. The laser pyrolysis of SiH4/GeH4 mixtures produced Si1 xGex alloy NPs. Effects of key process parameters including laser intensity and gas flow rates on NP properties have been investigated. The ability of the laser pyrolysis technique to flexibly produce a variety of germanium-containing NPs, as illustrated in this study shows promise for commercial-scale production of new nanomaterials as high purity dry powders. PMID- 26152900 TI - Improved black-blood imaging using DANTE-SPACE for simultaneous carotid and intracranial vessel wall evaluation. AB - PURPOSE: The purpose of this study was to develop a three-dimensional black blood imaging method for simultaneously evaluating the carotid and intracranial arterial vessel walls with high spatial resolution and excellent blood suppression with and without contrast enhancement. METHODS: The delay alternating with nutation for tailored excitation (DANTE) preparation module was incorporated into three-dimensional variable flip angle turbo spin echo (SPACE) sequence to improve blood signal suppression. Simulations and phantom studies were performed to quantify image contrast variations induced by DANTE. DANTE-SPACE, SPACE, and two-dimensional turbo spin echo were compared for apparent signal-to-noise ratio, contrast-to-noise ratio, and morphometric measurements in 14 healthy subjects. Preliminary clinical validation was performed in six symptomatic patients. RESULTS: Apparent residual luminal blood was observed in five (pre-contrast) and nine (post-contrast) subjects with SPACE and only two (post-contrast) subjects with DANTE-SPACE. DANTE-SPACE showed 31% (pre-contrast) and 100% (post-contrast) improvement in wall-to-blood contrast-to-noise ratio over SPACE. Vessel wall area measured from SPACE was significantly larger than that from DANTE-SPACE due to possible residual blood signal contamination. DANTE-SPACE showed the potential to detect vessel wall dissection and identify plaque components in patients. CONCLUSION: DANTE-SPACE significantly improved arterial and venous blood suppression compared with SPACE. Simultaneous high-resolution carotid and intracranial vessel wall imaging to potentially identify plaque components was feasible with a scan time under 6 min. Magn Reson Med 75:2286-2294, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26152901 TI - CFH polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration. AB - PURPOSE: To elucidate the potential role of single-nucleotide polymorphisms (SNPs) in complement factor H (CFH) gene in Northern Spanish patients with age related macular degeneration (AMD). METHODS: A case-control study of 130 unrelated native Northern Spanish diagnosed with AMD (46 dry, 35 neovascular and 49 mixed) and 96 healthy controls matched by age and ethnicity were enrolled. DNA was isolated from peripheral blood and genotyped for AMD-associated SNPs (rs3753394, rs529825, rs800292, rs3766404, rs203674, rs10671170, rs3753396 and rs1065489) using TaqMan probes and restriction fragment length polymorphism (RFLP). The association study was performed using the HaploView 4.0 software. RESULTS: The allelic frequency analysis revealed that rs529825, rs800292, rs203674 and rs10671170 were significantly associated with an increased risk for AMD. The haplotypes CGG (rs3753394, rs529825 and rs800292) and GCAG (rs203674, rs1061170, rs3753396 and rs1065489) were significantly associated with AMD while the haplotypes CAA (rs3753394, rs529825 and rs800292) and TTAG (rs203674, rs1061170, rs3753396 and rs1065489) were found to be protective. Small differ ences in allelic frequencies were found between dry and neovascular cases; however, these differences were not significant and did not distinguish one form the other. CONCLUSIONS: This study found significant association of SNPs rs529825, rs800292, rs203674 and rs1061170 in the CFH gene with susceptibility to AMD. We identified haplotypes that confer protection or increased risk of AMD but not specific genetic variants in CFH capable to distinguish the different clinical forms of AMD in this cohort. Collectively, our results confirmed that CFH represents a strong genetic risk factor for this disease in the Northern Spanish population. PMID- 26152902 TI - Investigation of ifosfamide and chloroacetaldehyde renal toxicity through integration of in vitro liver-kidney microfluidic data and pharmacokinetic-system biology models. AB - We have integrated in vitro and in silico data to describe the toxicity of chloroacetaldehyde (CAA) on renal cells via its production from the metabolism of ifosfamide (IFO) by hepatic cells. A pharmacokinetic (PK) model described the production of CAA by the hepatocytes and its transport to the renal cells. A system biology model was coupled to the PK model to describe the production of reactive oxygen species (ROS) induced by CAA in the renal cells. In response to the ROS production, the metabolism of glutathione (GSH) and its depletion were modeled by the action of an NFE2L2 gene-dependent pathway. The model parameters were estimated in a Bayesian context via Markov Chain Monte Carlo (MCMC) simulations based on microfluidic experiments and literature in vitro data. Hepatic IFO and CAA in vitro intrinsic clearances were estimated to be 1.85 x 10( 9) MUL s(-1) cell(-1) and 0.185 x 10(-9) MUL s(-1) cell(-1) ,respectively (corresponding to an in vivo intrinsic IFO clearance estimate of 1.23 l h(-1) , to be compared to IFO published values ranging from 3 to 10 l h(-1) ). After model calibration, simulations made at therapeutic doses of IFO showed CAA renal intracellular concentrations ranging from 11 to 131 MUM. Intracellular CAA concentrations above 70 MUM induced intense ROS production and GSH depletion. Those responses were time and dose dependent, showing transient and non-linear kinetics. Those results are in agreement with literature data reporting that intracellular CAA toxic concentrations range from 35 to 320 MUM, after therapeutic ifosfamide dosing. The results were also consistent with in vitro CAA renal cytotoxicity data. PMID- 26152903 TI - Does carbon reduction increase sustainability? A study in wastewater treatment. AB - This study investigates the relationships between carbon reduction and sustainability in the context of wastewater treatment, focussing on the impacts of control adjustments, and demonstrates that reducing energy use and/or increasing energy recovery to reduce net energy can be detrimental to sustainability. Factorial sampling is used to derive 315 control options, containing two different control strategies and a range of sludge wastage flow rates and dissolved oxygen setpoints, for evaluation. For each, sustainability indicators including operational costs, net energy and multiple environmental performance measures are calculated. This enables identification of trade-offs between different components of sustainability which must be considered before implementing energy reduction measures. In particular, it is found that the impacts of energy reduction measures on sludge production and nitrogen removal must be considered, as these are worsened in the lowest energy solutions. It also demonstrates that a sufficiently large range of indicators need to be assessed to capture trade-offs present within the environmental component of sustainability. This is because no solutions provided a move towards sustainability with respect to every indicator. Lastly, it is highlighted that improving the energy balance (as may be considered an approach to achieving carbon reduction) is not a reliable means of reducing total greenhouse gas emissions. PMID- 26152905 TI - Amphiphilic Pickering Emulsifiers Based on Mushroom-Type Janus Particles. AB - Iron-based mushroom-type Janus particles consisting of a poly(sytrene-co divinylbenzene) and a silica moiety both with controllable morphologies were successfully synthesized on the gram scale and investigated as surfactants for Pickering emulsions. Two oil-water model systems, namely toluene-water and vegetable oil-water, were stabilized, giving mainly water-in-oil (w/o) emulsions. By varying several parameters, including Janus particle morphologies and the oil water ratio, fine-tuning of the emulsion systems was possible; it was even possible to invert the continuous phase to an oil-in-water (o/w) system. Furthermore, the emulsions were stable against coalescence and sedimentation and could be easily separated by centrifugation or a strong magnet. The synthesized mushroom-type Janus particles are suitable for creating Pickering emulsions and can be used as building blocks for creating nanostructures with tailored properties for specific applications. PMID- 26152906 TI - Reducing alternate level of care days at Winchester District Memorial Hospital. AB - Winchester District Memorial Hospital has maintained near-zero alternative level of care census days for three consecutive years by focusing on partnerships, staff/physician engagement, and maintaining a circle of care with patients and families. The strategies and challenges faced revisiting internal discharge processes and linking directly to their local community through change management techniques are discussed. PMID- 26152904 TI - Anti-cancer effects of enteric-coated polymers containing mistletoe lectin in murine melanoma cells in vitro and in vivo. AB - In this study, we evaluated the effects of Korean mistletoe (Viscum album L. var. coloratum) coated with a biodegradable polymer (Eudragit((r))) wall on the growth of mouse melanoma in vivo. Oral administration of 4% (430 mg/kg/day) enteric coated mistletoe resulted in a significant reduction in tumor volume on day 14 compared to the negative control group in B16F10 melanoma-inoculated BDF1 mice. When we measured the survival rate, enteric-coated mistletoe-received mice had a higher survival rate after day 12. Also, we investigated the mechanism involving the cancer cell growth inhibition when melanoma cells were treated with Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) and its extract in vitro. As a result, a significant G0/G1 arrest was observed in both B16BL6 and B16F10 melanoma cells with VCA or mistletoe extract. In addition, VCA or mistletoe extract induced an increase in both early and late apoptosis in cells. When we studied the molecular mechanism, our results showed that VCA and mistletoe extract can increase activated multiple caspases (caspase-1, 3, 4, 5, 6, 7, 8, and 9), dose-dependently. We also found out that VCA and mistletoe treatment causes a significant decrease in the expression of procaspase-3 and 8. PMID- 26152907 TI - Navigating stormy waters in times of fiscal uncertainty: Mitigating the challenges. AB - New approaches to resource allocation are providing healthcare managers with ways to meet budget pressures while maximizing benefit to patients and populations. But putting these approaches in place often involves significant organizational change to which some degree of resistance must be expected. The authors have seen seven common objections raised time and again. Here, we offer our best advice on how healthcare leaders can anticipate and respond proactively to these challenges. PMID- 26152908 TI - Prenatal stress produces sex-specific changes in depression-like behavior in rats: implications for increased vulnerability in females. AB - Stress during rat gestation can elicit depression-like physiological and behavioral responses in the offspring. However, human clinical depression is more prevalent among females than males. Accordingly, we examined how repeated variable prenatal stress (PS) alters rat anxiety- and depression-like behavior as well as circadian patterning of motor activity in both male and female offspring. For this purpose, we exposed pregnant Sprague-Dawley rats to multiple stressors during gestational days 13-21. Subsequently, we monitored locomotor and rearing/climbing activities in home-like cages for 24 h and measured anxiety- (elevated plus maze, EPM) and depression-like (forced swim test, FST) behaviors in the offspring at a young adult age. As a stressful event later in life (in addition to PS) may be needed to actually trigger an episode of clinical depression, half of the animals were exposed to an acute stressor (elevated platform) before EPM testing. Dams exposed to the stressor battery had increased plasma corticosterone levels compared with controls. Male PS offspring displayed changes in locomotor and rearing/climbing activity relative to controls. Additionally, anxiety measures in the EPM were affected in control animals after acute stressor exposure, however, this response was blunted in PS offspring. Moreover, FST immobility, as an indicator of depressive-like behavior, was increased in female but not male PS rats. Altogether, our results identify both sex- and circadian phase-specific effects of PS. These findings indicate that the PS rat model reflects multiple clinical depression characteristics, including elevated female vulnerability. PMID- 26152909 TI - Why does increasing public access to medicines differ between countries? Qualitative comparison of nine countries. AB - OBJECTIVE: To identify factors associated with differences between developed countries in reclassifying (switching) medicines from prescription to non prescription availability. METHODS: Cross-national qualitative research using a heuristic approach in the US, UK, Japan, Australia and New Zealand, supplemented by data from Canada, Denmark, the Netherlands and Singapore. In-depth interviews with 80 key informants (65 interviews) explored and compared factors in terms of barriers and enablers to reclassification of medicines in each country. Document analysis supplemented interview data. RESULTS: Each country had a unique mix of enablers and barriers to reclassification. Enablers included government policy (particularly in UK), pharmacist-only scheduling (particularly in Australia and New Zealand) and large market size (particularly in the US and Europe). Local barriers included limited market potential in small countries, the cost of a reclassification (particularly in the US), competition from distributors of generic medicines, committee inconsistency and consumer behavior. UK had more enablers than barriers, whereas in Australia the opposite was true. CONCLUSIONS: Different factors limit or enable reclassification, affecting consumer access to medicines in different countries. For countries attempting to reduce barriers to reclassification, solutions may include garnering government support for reclassification, support and flexibility from the medicines regulator, having a pharmacy-only and/or pharmacist-only category, providing market exclusivity, ensuring best practice in pharmacy, and minimizing the cost and delays of reclassification. PMID- 26152910 TI - Clinical factor for successful nonsurgical treatment of pediatric peritonsillar abscess. AB - OBJECTIVES/HYPOTHESIS: Current management for peritonsillar abscess in pediatric patients includes intensive medical therapy using antibiotics with or without surgical drainage. However, attaining proper surgical drainage is difficult in young children because they have narrow oral cavities and are less cooperative than adults. The aim of this study was to investigate which factors are associated with a good response to nonsurgical treatment of a pediatric peritonsillar abscess. STUDY DESIGN: A retrospective analysis. METHODS: This study included consecutive children who visited our pediatric clinic for the treatment of peritonsillar abscess. All patients initially received medical treatment, and additional surgical treatment was provided if the patient appeared unlikely to recover. Multivariate logistic regression models were constructed to identify factors associated with a good response to nonsurgical treatment. In addition, a receiver operating characteristic curve was used to identify the age cutoff for predicting good treatment response. RESULTS: A total of 88 children were included the study. Patient age, recurrent tonsillitis, and abscess size were significantly associated with response to nonsurgical treatment (adjusted odds ratios=1.485, 2.403, and 1.325, respectively) after adjusting for sex, body mass index, season, serum C-reactive protein levels, and tonsil grade. The age cutoff associated with good response to nonsurgical treatment was 7.5 years (80.0% sensitivity, 51.5% specificity). CONCLUSION: Our findings suggest that a younger age, fewer episodes of acute tonsillitis, and smaller abscess size predict a successful response to nonsurgical treatment in children with peritonsillar abscess. LEVEL OF EVIDENCE: 4. PMID- 26152911 TI - Carrier generation and recombination dynamics in type-II ZnSeTe/ZnMnSe quantum structures. AB - Type-II band alignment structure is coveted in the design of photovoltaic devices, since it is beneficial for the transport of photogenerated carriers. Here we study the generation and recombination dynamics of carriers in a type-II quantum structure composed of ZnSe0.92Te0.08 highly mismatched alloys (HMAs) and Zn0.97Mn0.03Se. The photoinduced holes at the ZnSe0.92Te0.08 HMAs firstly undergo rapid relaxation to the isoelectronic centers above the valence band edge and subsequently recombine with the free electrons in the Zn0.97Mn0.03Se. The long carrier lifetimes over 120 ns induced by spatially indirect excitons that are bound to isoelectronic Te trapping states further increase with increasing temperature. PMID- 26152912 TI - Safety concerns of herbal products and traditional Chinese herbal medicines: dehydropyrrolizidine alkaloids and aristolochic acid. AB - In many countries, including the United States, herbal supplements, tisanes and vegetable products, including traditional Chinese medicines, are largely unregulated and their content is not registered, monitored or verified. Consequently, potent plant toxins including dehydropyrrolizidine alkaloids and other potential carcinogens can contaminate these products. As herbal and food supplement producers are left to their own means to determine the safety and purity of their products prior to marketing, disturbingly often good marketing practices currently in place are ignored and content is largely undocumented. Historical examples of poisoning and health issues relating to plant material containing dehydopyrrolizidine alkaloids and aristolochic acids were used as examples to demonstrate the risk and potential toxicity of herbal products, food supplements, or traditional medicines. More work is needed to educate consumers of the potential risk and require the industry to be more responsible to verify the content and insure the safety of their products. PMID- 26152914 TI - High efficiency silicon solar cell based on asymmetric nanowire. AB - Improving the efficiency of solar cells through novel materials and devices is critical to realize the full potential of solar energy to meet the growing worldwide energy demands. We present here a highly efficient radial p-n junction silicon solar cell using an asymmetric nanowire structure with a shorter bottom core diameter than at the top. A maximum short circuit current density of 27.5 mA/cm(2) and an efficiency of 7.53% were realized without anti-reflection coating. Changing the silicon nanowire (SiNW) structure from conventional symmetric to asymmetric nature improves the efficiency due to increased short circuit current density. From numerical simulation and measurement of the optical characteristics, the total reflection on the sidewalls is seen to increase the light trapping path and charge carrier generation in the radial junction of the asymmetric SiNW, yielding high external quantum efficiency and short circuit current density. The proposed asymmetric structure has great potential to effectively improve the efficiency of the SiNW solar cells. PMID- 26152913 TI - Multicentre investigation of pathogenic bacteria and antibiotic resistance genes in Chinese patients with acute exacerbation of chronic obstructive pulmonary disease. AB - OBJECTIVE: A prospective observational study to investigate the distribution and antimicrobial resistance of pathogenic bacteria in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing, China. METHODS: Patients with AECOPD were recruited from 11 general hospitals. Sputum specimens were cultured and bacteria identified. Antibiotic susceptibility was determined for each isolate, and presence of antibiotic resistance genes was evaluated using polymerase chain reaction. RESULTS: Pathogenic bacteria were isolated from 109/318 patients (34.28%); 124 isolates of 22 pathogenic bacterial species were identified, including Klebsiella pneumoniae (16.94%), Pseudomonas aeruginosa (16.94%), Acinetobacter baumannii (11.29%), Streptococcus pneumoniae (8.87%), and Staphylococcus aureus (7.26%). S. aureus was sensitive to tigecycline, teicoplanin, vancomycin and linezolid but resistant to penicillin and levofloxacin. K.pneumoniae, P. aeruginosa, A. baumannii and E. coli were susceptible to amikacin and cefoperazone. CONCLUSIONS: K. pneumoniae and P. aeruginosa are the most common pathogenic bacteria in AECOPD cases in Beijing, China. Our antibiotic resistance findings may be helpful in selecting antibiotic therapy. PMID- 26152915 TI - A centrally acting antihypertensive, clonidine, combined to a venous dilator, nitroglycerin, to handle severe pulmonary edema. AB - A patient, with known left ventricular failure presented with severe pulmonary edema, an ejection fraction of 10% to 15%, knee mottling, and lactates of 7 mM L 1. He was treated with unusually high-dose nitroglycerin (NTG) intravenously (IV; NTG ~ 70 mg for 1 hour). To suppress dyspnea, systolic blood pressure had to be lowered from ~ 150-160 to ~ 100-120 mm Hg. To lower NTG requirement, an alpha-2 agonist, clonidine, was administered (300 MUg IV for 2 hours). Dyspnea, tachypnea, and tachycardia subsided for 1 to 2 hours, allowing to reduce NTG infusion to 2 to 4 mg h-1. State-of the-art treatment was superimposed: sitting position with leg down, noninvasive ventilation, positive end-expiratory pressure, bolus of furosemide 250 mg, and administration of 1000 mL of crystalloid for 1 hour under echocardiographic guidance. We ascribed the resistance to NTG to the activation of the sympathetic, vasopressin, and renin angiotensin systems ("neurohormonal activation"). alpha-2 agonists reduce the sympathetic activation observed during severe left ventricular failure and overall oxygen consumption, evoke systemic and pulmonary arterial dilation, increase diastolic time, and improve diastolic function and diuresis. Because the alpha-2 agonist, dexmedetomidine, is available as an IV drug on the North American market, a niche may exist in the setting of emergency medicine/coronary care. This awaits evidence-based documentation. PMID- 26152916 TI - Emergent diagnostic testing for pediatric nonfebrile seizures. AB - BACKGROUND: Guidelines from the American Academy of Neurology recommend laboratory studies or computed tomography (CT) for children who experience a nonfebrile seizure if anything in their history suggests a clinically significant abnormality. OBJECTIVE: To ascertain if any patient or seizure characteristics are associated with a greater likelihood that laboratory studies or CT scan will yield clinically significant results. METHODS: This retrospective case series reviewed 93 children with nonfebrile seizure, who were evaluated in an urban pediatric emergency department (ED) between July 2007 and June 2011. RESULTS: Laboratory studies were performed in 87% of the study group; 7% of those tests gave clinically significant results. Computed tomographic scans were obtained in 35% of our patients; 9% showed clinically significant findings. Presence of an active seizure in the ED or a first nonfebrile seizure had an 8% and 11% difference, respectively, for clinically significant laboratory abnormality. Children younger than 2 years showed a 7% difference of clinically significant laboratory abnormality. CONCLUSION: This study did not identify statistically significant predictors of laboratory or CT abnormalities for children with nonfebrile seizure presenting to the ED. Age less than 2years, having an active seizure in the ED, and experiencing a first-time seizure showed a trend toward an increased yield of laboratory testing. In accordance with the American Academy of Neurology guidelines, we conclude that the history of a child's present illness preceding the nonfebrile seizure, not characteristics of the seizure, should be used to determine the need for further testing. PMID- 26152920 TI - Shades of T790M: Intratumor Heterogeneity in EGFR-Mutant Lung Cancer. AB - In the setting of recent exciting clinical results and numerous ongoing trials, Piotrowska and colleagues explore mechanisms of acquired resistance to the mutant specific EGFR inhibitor rociletinib, and demonstrate that loss of T790M, EGFR amplification, and small-cell transformation are all clinically relevant mechanisms of drug resistance. The authors provide a new paradigm for using quantitative assessment of the EGFR T790M:activation mutation allele frequency ratio to prognosticate responses to rociletinib and also demonstrate that plasma based assessments of circulating tumor DNA can be used to monitor drug response and the emergence of drug resistance. PMID- 26152922 TI - Targeting MYC Translation in Colorectal Cancer. AB - There is a great interest in finding ways to inhibit the expression or activity of the "undruggable" MYC, a master regulator of transcription and one of the most deadly oncoproteins in human cancer. In this issue of Cancer Discovery, Wiegering and colleagues find a way of inhibiting translation of MYC in colorectal cancer cells by directly targeting the translation initiation factor eIF4A, resulting in inhibition of MYC-dependent proliferation of colorectal tumor cells in vitro and in vivo. PMID- 26152921 TI - INPP4B Is a Tumor Suppressor in the Context of PTEN Deficiency. AB - Enzymes (PI3K and PTEN) controlling cellular levels of 3-phosphorylated phosphoinositides are known as important drivers or suppressors of tumorigenesis in various cancers. In this issue of Cancer Discovery, Kofuji and colleagues and Chew and colleagues identify the lipid phosphatase INPP4B as a context-specific tumor suppressor that controls phosphoinositide levels and AKT2 activation in PTEN-deficient cells. PMID- 26152929 TI - Complementary DNA display selection of high-affinity peptides binding the vacuolating toxin (VacA) of Helicobacter pylori. AB - Artificial peptides designed for molecular recognition of a bacterial toxin have been developed. Vacuolating cytotoxin A protein (VacA) is a major virulence factor of Helicobacter pylori, a gram-negative microaerophilic bacterium inhabiting the upper gastrointestinal tract, particularly the stomach. This study attempted to identify specific peptide sequences with high affinity for VacA using systematic directed evolution in vitro, a cDNA display method. A surface plasmon resonance-based biosensor and fluorescence correlation spectroscopy to examine binding of peptides with VacA identified a peptide (GRVNQRL) with high affinity. Cyclization of the peptide by attaching cysteine residues to both termini improved its binding affinity to VacA, with a dissociation constant (Kd ) of 58 nm. This study describes a new strategy for the development of artificial functional peptides, which are promising materials in biochemical analyses and medical applications. PMID- 26152930 TI - Developmental origins, behaviour change and the new public health. AB - A developmental approach to public health focuses attention on better nourishing girls and young women, especially those of low socio-economic status, to improve mothers' nutrition and thereby the health of future generations. There have been significant advances in the behavioural sciences that may allow us to understand and support dietary change in young women and their children in ways that have not previously been possible. This paper describes some of these advances and aims to show how they inform this new approach to public health. The first of these has been to work out what is effective in supporting behaviour change, which has been achieved by careful and detailed analysis of behaviour change techniques used by practitioners in intervention, and of the effectiveness of these in supporting change. There is also a new understanding of the role that social and physical environments play in shaping our behaviours, and that behaviour is influenced by automatic processes and 'habits' as much as by reflective processes and rational decisions. To be maximally effective, interventions therefore have to address both influences on behaviour. An approach developed in Southampton aims to motivate, support and empower young women to make better food choices, but also to change the culture in which those choices are being made. Empowerment is the basis of the new public health. An empowered public demand for better access to better food can go a long way towards improving maternal, infant and family nutrition, and therefore the health of generations to come. PMID- 26152931 TI - B cell expression of the SH2-containing inositol 5-phosphatase (SHIP-1) is required to establish anergy to high affinity, proteinacious autoantigens. AB - Many self-reactive B cells exist in the periphery in a rapidly reversible state of unresponsiveness referred to as anergy. Reversibility of anergy indicates that chronically occupied BCR must transduce non-durable regulatory signals that maintain unresponsiveness. Consistent with such a mechanism, studies of immunoglobulin transgenic, as well as naturally occurring polyclonal autoreactive B cells demonstrate activation of the inositol 5-phosphatase SHIP-1 in anergic cells, and low affinity chromatin autoantigen-reactive B cells have been shown to require expression of this phosphatase to maintain anergy. However, it has been reported that anergy of B cells recognizing high affinity soluble antigen may not require SHIP-1, and is instead mediated by upregulation of the inositol 3 phosphatase PTEN. To further explore this apparent difference in mechanism we analyzed the effect of B cell-targeted SHIP-1 deletion on immune tolerance of high affinity anti-HEL B cells in mice expressing soluble HEL (MD4.ML-5). We report that SHIP-1 functions to dampen responses of naive and low-dose antigen primed B cells in vitro, and is required for induction of B cell tolerance. Thus, while anergy of B cells reactive with low affinity and likely polyvalent chromatin antigens is maintained by activation of inhibitory signaling circuitry involving SHIP-1, anergy of B cells recognizing soluble self antigen with high affinity also requires increased activity of SHIP-1. PMID- 26152932 TI - Early ALS-type gait abnormalities in AMP-dependent protein kinase-deficient mice suggest a role for this metabolic sensor in early stages of the disease. AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motoneurons. While the principal cause of the disease remains so far unknown, the onset and progression of the pathology are increasingly associated with alterations in the control of cell metabolism. On the basis of the well-known key roles of 5'-adenosine monophosphate-activated protein kinase (AMPK) in sensing and regulating the intracellular energy status, we hypothesized that mice with a genetic deletion of AMPK would develop locomotor abnormalities that bear similarity with those detected in the very early disease stage of mice carrying the ALS-associated mutated gene hSOD1(G93A). Using an automated gait analysis system (CatWalk), we here show that hSOD1(G93A) mice and age-matched mice lacking the neuronal and skeletal muscle predominant alpha2 catalytic subunit of AMPK showed an altered gait, clearly different from wild type control mice. Double mutant mice lacking AMPK alpha2 and carrying hSOD1(G93A) showed the same early gait abnormalities as hSOD1(G93A) mice over an age span of 8 to 16 weeks. Taken together, these data support the concept that altered AMPK function and associated bioenergetic abnormalities could constitute an important component in the early pathogenesis of ALS. Therapeutic interventions acting on metabolic pathways could prove beneficial on early locomotor deficits, which are sensitively detectable in rodent models using the CatWalk system. PMID- 26152933 TI - Cyclic acetals as cleavable linkers for affinity capture. AB - Labeling proteins with biotin is a widely used method to identify target proteins due to biotin's strong binding affinity for streptavidin. Combined with alkyne azide cycloaddition, which enables the coupling of probes to targeted proteins, biotin tags linked to an alkyne or azide have become a powerful tool for purification and analysis of proteins in proteomics. However, biotin requires harsh elution conditions to release the captured protein from the bead matrix. Use of these conditions reduces signal to noise and complicates the analysis. To improve affinity capture, cleavable linkers have been introduced. Here, we demonstrate the use of a cyclic acetal biotin probe that is prepared easily from commercially available starting materials, is stable to cell lysates, yet is cleaved under mildly acidic conditions, and which provides an aldehyde for further elaboration of the protein, if desired. PMID- 26152934 TI - Real-Time Volumetric Phase Monitoring: Advancing Chemical Analysis by Countercurrent Separation. AB - Countercurrent separation (CCS) utilizes the differential partitioning behavior of analytes between two immiscible liquid phases. We introduce the first platform ("CherryOne") capable of real-time monitoring, metering, and control of the dynamic liquid-liquid CCS process. Automated phase monitoring and volumetrics are made possible with an array of sensors, including the new permittivity-based phase metering apparatus (PMA). Volumetric data for each liquid phase are converted into a dynamic real-time display of stationary phase retention (Sf) and eluent partition coefficients (K), which represent critical parameters of CCS reproducibility. When coupled with the elution-extrusion operational mode (EECCC), automated Sf and K determination empowers untargeted and targeted applications ranging from metabolomic analysis to preparative purifications. PMID- 26152936 TI - Keynotes. PMID- 26152937 TI - An Introduction to Structural Equation Modeling. AB - In this contribution the principles behind Structural Equation Modeling (SEM) are presented. SEM is used for assessing the quality of models that are proposed on the basis of theory and experience. This contribution has an introductory level. PMID- 26152935 TI - Physical Activity from Early Adulthood and Risk of Prostate Cancer: A 24-Year Follow-Up Study among Icelandic Men. AB - Physical activity in adult life may reduce prostate cancer risk. Data are scarce on the role of activity during early adulthood, as well as combined recreational and occupational physical activity on prostate cancer risk and mortality. We undertook a prospective study of 8,221 Icelandic men (born 1907 to 1935) in the population-based Reykjavik Study. At enrollment, between 1967 and 1987, the men provided information on regular recreational physical activity since the age of 20 years as well as current occupational activity. Through linkage to nationwide cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality through 2009. We used Cox models to calculate the relative risk of prostate cancer by level of physical activity. During a mean follow-up of 24.8 years, 1,052 men were diagnosed with prostate cancer, of whom 349 had advanced disease (stage 3+ or prostate cancer death). Neither recreational nor occupational physical activity was, independently or combined, associated with overall or localized prostate cancer. Compared with physically inactive men, we observed a nonsignificant lower risk of advanced prostate cancer [HR, 0.67; 95% confidence interval (CI), 0.42-1.07] among men reporting both recreational and occupational physical activities (P value for interaction = 0.03). Awaiting confirmation in larger studies with detailed assessment of physical activity, our data suggest that extensive physical activity beginning in early adulthood may reduce the risk of advanced prostate cancer. PMID- 26152938 TI - Privacy and Data Protection in Healthcare: eHealth for All - Keynote Address. PMID- 26152939 TI - Biomedical Technology. PMID- 26152940 TI - Photodocumentation of Allergic Severity under Conjunctival Provocation. AB - The aim of this work was to evaluate conjunctival redness as an objective allergy symptom during the conjunctival provocation test (CPT). The CPT is an instillation of ophthalmic solution containing an allergen into the ocular mucosa. Allergic severity using the CPT was evaluated in the multicenter, randomized, controlled, double-blind, dose-finding study of 159 patients with birch pollen allergy where the mucosal sensitivity of the eye was assessed based on subjective and objective symptoms such as itching and redness, respectively. High-resolution digital photos were taken, arranged in image matrices, and analyzed by an external central observer to assess conjunctival redness. The photodocumentation method described here was successfully applied in a dose finding study using the CPT. The evaluations of allergic severity carried out by an external observer agreed with the investigators' assessments. PMID- 26152941 TI - Image-Based Assessment of Allergic Inflammation under Conjunctival Provocation. AB - Conjunctival redness is an objective allergy symptom which can be analyzed using objective computer imaging methods. To evaluate allergic inflammation of the eyes, a robust and precise image-based method was developed and applied to analyze allergic hyperemia under the conjunctival provocation test (CPT). High resolution digital photos were taken and analyzed via digital analysis software to obtain and document conjunctival redness. The evaluations made using this newly developed image-based method concurred with the study investigators' assessments: the therapeutic effects of the highest doses were superior to the lowest dose. PMID- 26152942 TI - 3D Texture Analysis of Heterogeneous MRI Data for Diagnostic Classification of Childhood Brain Tumours. AB - Brain tumours are the most frequently occuring solid tumours affecting childhood, representing 27% of all cancers. The most common posterior fossa tumours are medulloblastoma, pilocytic astrocytoma and ependymoma. Texture Analysis (TA) of Magnetic Resonance Imaging (MRI) aims to represent pixel distributions, intensities and dependencies using mathematically defined features. Such features could potentially provide quantifiable information that is beyond the human vision capabilities, and hence be used to supplement qualitative assessments conducted by radiologists. The primary aim of this study was to carry out a multicentre investigation on the efficacy of 3D TA for diagnostic classification of childhood brain tumours, using conventional MRI images. The data used had been acquired at three different hospitals and consisted of pre-contrast T1 and T2 weighted MRI series, obtained from 121 children diagnosed with medulloblastoma, pilocytic astrocytoma and ependymoma. Using 3D textural features, based on first, second and higher order statistical methods, a support vector machine (SVM) classifier was trained and tested using the leave-one-out cross-validation (LOOCV) approach. An essential outcome of this study is that 3D TA demonstrated a good overall performance, when used on data acquired from a number of centres and using scanners made by different manufacturers and at different magnetic field strengths. PMID- 26152944 TI - Clinical Informatics. PMID- 26152943 TI - Establishing a National Medical Device Registry in Saudi Arabia: Lessons Learned and Future Work. AB - Medical device evaluation presents several unique challenges due to the great diversity and complexity of medical devices and their rapid technological evolution. There has been a variety of work conducted on the development of disease based registries and health surveillance systems in Saudi Arabia. However, the progress of medical device registry systems and post-market medical device surveillance systems remains in its infancy in Saudi Arabia and within the region. In 2007, a royal decree assigned the responsibility for regulating medical devices to the Saudi Food and Drug Authority (SFDA). Soon afterwards, the SFDA established the Medical Devices National Registry (MDNR) to house medical device information relating to manufacturers, agents, suppliers and end-users. The aim of this paper is to provide an overview on the Medical Device National Registry (MDNR) in Saudi Arabia and describe the current experience and future work of establishing a comprehensive medical device registry and post-market surveillance system in Saudi Arabia. PMID- 26152945 TI - The Implementation Experiences of an Endoscopy Information System (EIS) on the Improvement of Workflow Processes in a Saudi Endoscopy Department. AB - The objective of this paper is to investigate the experiences in implementing a smart capsule system for a Saudi endoscopy department. The study was conducted at a leading Saudi healthcare institution located in Riyadh, Saudi Arabia. A case study approach was used in the study. Endoscopy Information System (EIS) system data documentation, key informant interviews, and meeting documents were the data collection sources used in the study. A thematic analysis of the data was conducted. Preliminary data showed improvements in hospital clinical workflow as a result of implementing the new EIS. Although the findings of this study are preliminary, more work is needed to evaluate the overall impact of the new EIS on clinical workflow, patient wait times, usability, and data accuracy. PMID- 26152946 TI - Remote Patient Monitoring System Implementation at a Cardiac Care Centre in Saudi Arabia. AB - The objective of this paper is to report the implementation experiences of a remote patient monitoring system at a cardiac care center in Saudi Arabia. Key informant interviews, meeting documents, and experience of the researcher were part of the data collection sources used in the study. A thematic analysis of the data was conducted. Our preliminary work shows improvements in patient monitoring within the cardiac care center as a result of the new patient monitoring system. Lessons learned are also reported as well as study limitations. Future work will further investigate the impacts of the patient monitoring system on physician and patient satisfaction and health outcomes. PMID- 26152947 TI - Vagal Nerve Stimulation (VNS) Therapy System Implementation at a Neurology Department in Saudi Arabia. AB - The objective of this paper is to report on the implementation of a Vagal Nerve Stimulation (VNS) Therapy System at a neurology department in Saudi Arabia. Key informant interviews, meeting documents, and experience of the researcher were part of the data collection sources used in the study. A thematic analysis of the data was conducted. The preliminary work shows improvements in epilepsy treatment within the neurology department as a result of the new Vagal Nerve Stimulation (VNS) therapy system. We discuss the lessons learned and identify the limitations of the study. Future work will further investigate the impacts of the VNS system on physician and patient satisfaction and health outcomes. PMID- 26152948 TI - Improving Emergency Room Performance by Reducing Patients' Length of Stay. AB - Improving the performance of Emergency Room (ER) has become a major concern for both healthcare professionals and researchers. ER patients' length of stay is one of the most important indicators for performance monitoring as well as improvement. The main objective of this study is to evaluate the effects of enhancing ER information accessibility of nurses, through a special ER nurses training program, on reducing patients' length of stay. Data on 5,769 ER encounters were retrospectively retrieved and analyzed to compare ER length of stay and related intervals of the first quarter of 2015, after implementing the training program, to the first quarter of 2014, before implementing the program. There was a 25.5% improvement on "Arrival to Triage" interval, 17.7% improvement on "Triage to ER Bed", 16.1% improvement on "ER Bed Assigned to Doctor Examination" and 13.2% improvement on "Doctor Examination to Discharge" interval. The total ER length of stay was improved by 13.7%. PMID- 26152949 TI - A First Step for the Automation of Fugl-Meyer Assessment Scale for Stroke Subjects in Upper Limb Physical Neurorehabilitation. AB - This paper proposes a first approach for the automation of the Fugl-Meyer assessment scale used in physical neurorehabilitation. The main goal of this research is to automatically estimate an objective measurement for five Fugl Meyer scale items related to the assessment of the upper limb motion. An objective score has been calculated for 7 patients. Obtained results indicate that the automation of the scale can be a useful tool for the objective assessment of upper limb motion of stroke survivors. PMID- 26152950 TI - An Extensible Neuroimaging e-Repository for Clinical Trials of Paediatric Brain Tumours. AB - Novel imaging techniques are playing an increasing role in tumour characterisation, assessment and management. However, incorporating imaging data into clinical trials presents a number of challenges in terms of quality control, standardisation in data collection, interoperability of widely used archiving systems and extensibility of imaging software architectures. Additionally, currently available monolithic applications cannot fulfil the diverse and rapidly changing needs of the clinical imaging research community. This paper discusses the limitations of the current CCLG Remote Data Entry (RDE) system and introduces the prototype of an alternative modular system based on the Extensible Neuroimaging Archive Toolkit (XNAT). The modular nature of the presented prototype promotes incremental software evolution and allows for flexible system customisation to suit the needs of individual imaging centres. PMID- 26152951 TI - Computerized Insulin Order Sets Can Lead to Unanticipated Consequences. AB - Computerized order sets for medication management were recently shown to be associated with increased patient safety risks in primary care setting. This study was aimed at demonstrating similar phenomenon in a hospital setting. After introduction of computerized order set targeting hypoglycemia, the frequency of hypoglycemia significantly decreased from 1/1/07 to 12/31/08. However, the frequency of hyperglycemia also increased at the same time from 1/1/07 to 12/31/07. Only after subsequent introduction of a hospital-wide standardized insulin order set including hyperglycemia policies, the frequency of hyperglycemic episodes declined. Hypo/hyperglycemia is associated with adverse clinical outcomes in the inpatient setting. Retroactive analysis showed that if hypoglycemic and hyperglycemic policies were introduced simultaneously, unexpected increase in frequency of hyperglycemic episodes could have been avoided. These data are informative in identifying unanticipated consequences of an insulin management order sets focused entirely on hypoglycemia. A balanced approach in implementing insulin management EMR order sets that concurrently addresses both hypoglycemia and hyperglycemia policies is warranted. PMID- 26152952 TI - A Query Tool Enabling Clinicians and Researchers to Explore Patient Cohorts. AB - Due to the increasing amount of health information being gathered and the potential benefit of data reuse, it is now becoming a necessity for tools, which collect and analyse this data, to support integration of heterogeneous datasets, as well as provide intuitive user interfaces, which allow clinicians and researchers to query the data without needing to form complex SQL queries. The West Midlands Query Tool consists of an easy-to-use graph-based GUI, which interacts with a flexible middleware application. It has the main objective of querying heterogeneous data sources for exploring patient cohorts through a query builder and criteria set. PMID- 26152954 TI - Decision Support and Intelligent Systems. PMID- 26152953 TI - Feasibility of Interactive Resistance Chair in Older Adults with Diabetes. AB - An interactive resistance chair (RC) exercise system has been designed to support patients at home in following their individualized strengthening exercise plan. The aim of this study was (1) to introduce a computer-assisted home-based resistance exercise for older adults and (2) to demonstrate feasibility of the proposed system in older adults with diabetes. The RC exercise system was well accepted by older adults with diabetes regardless of education level, race or gender. The post-task questionnaires demonstrated ease of system use and satisfaction with the system. The attitudinal survey results showed positive seniors' attitudes towards the RC exercise system. The system usability (SUS) scale score was 94.0+/-5.76 demonstrating high acceptance of the RC exercise system. From the qualitative interviews, individualized feedback yielded important system upgrade solutions that can be useful in tailoring patient needs, values and preferences specific for seniors with diabetes. Further research is warranted to assess impact of RC exercise system in home setting with a larger sample size in a randomized trial. PMID- 26152955 TI - Clinical Decision Support Knowledge Management: Strategies for Success. AB - Clinical Decision Support Systems have been shown to increase quality of care, patient safety, improve adherence to guidelines for prevention and treatment, and avoid medication errors. Such systems depend mainly on two types of content; the clinical information related to patients and the medical knowledge related to the specialty that informs the system rules and alerts. At King Faisal Specialist Hospital and Research Center, Saudi Arabia, the Health Information Technology Affairs worked on identifying best strategies and recommendations for successful CDSS knowledge management. A review of literature was conducted to identify main areas of challenges and factors of success. A qualitative survey was used over six months' duration to collect opinions, experiences and suggestions from both IT and healthcare professionals. Recommendations were categorized into ten main topics that should be addressed during the development and implementation of CDSS knowledge management tools in the hospital. PMID- 26152956 TI - The Prognostic Scale CRASH in the Treatment of Children with Severe Traumatic Brain Injury. AB - The aim of the present study was to assess the effectiveness and validity of prognostic scale CRASH which is calculated using on-line resources and which may serve as a decision support for physicians in treating severe traumatic brain injury (TBI) in children. This retrospective study was conducted using clinical and physiological data of 168 hospitalized pediatric patients with severe traumatic brain injury (GCS score less than or equal to 8). CRASH scale was used for calculating the severity of patients' state and for prognosing death outcomes at 14 days and at 6 months using the on-line resource. Our research has shown that the prognostic scale CRASH has an excellent discrimination ability (AUROC=0.816) in each version. The study has also shown that the scale has a satisfactory calibration ability in the option of 14 days with CT (chi2 equal 8.7 and p-value equal to 0.368). Calibration ability for other options was unsatisfactory. Thus, CRASH scale with CT scan has turned to be useful for assessing death outcomes at 14 days in children with severe TBI. PMID- 26152957 TI - Prediction of 5-Year Survival with Data Mining Algorithms. AB - Survival time prediction at the time of diagnosis is of great importance to make decisions about treatment and long-term follow-up care. However, predicting the outcome of cancer on the basis of clinical information is a challenging task. We now examined the ability of ten different data mining algorithms (Perceptron, Rule Induction, Support Vector Machine, Linear Regression, Naive Bayes, Decision Tree, k-nearest Neighbor, Logistic Regression, Neural Network, Random Forest) to predict the dichotomous attribute "5-year-survival" based on seven attributes (sex, UICC-stage, etc.) which are available at the time of diagnosis. For this study we made use of the nationwide German research data set on colon cancer provided by the Robert Koch Institute. To assess the results a comparison between data mining algorithms and physicians' opinions was performed. Therefore, physicians guessed the survival time by leveraging the same seven attributes. The average accuracy of the physicians' opinion was 59%, the average accuracy of the machine learning algorithms was 67.7%. PMID- 26152958 TI - Abstractive Summarization of Drug Dosage Regimens for Supporting Drug Comparison. AB - Complicated dosage regimens often reduce adherence to drug treatments. The ease of-administration must thus be taken into account when prescribing. Given one drug, there exists often several dosage regimens. Hence, comparison to similar drugs is difficult. Simplifying and summarizing them appears to be a required task for supporting General Practitioners to find the drug with the simplest regimen for the patient. We propose a summarization in two steps: first prunes out all low-importance information, and second proceed to fusion of remaining information. Rules for pruning and fusion strategies were designed by an expert in drug models. Evaluation was conducted on a dataset of 169 drugs. The agreement rate was 27.2%. We demonstrate that applying rules leads to a result that is correct by a computational point of view, but the result is often meaningless for the GP. We conclude with recommendations for further work. PMID- 26152959 TI - Exploitation of Medical Crisp Database for Fuzzy Diagnostic Decision Support Systems. AB - There are several types of Diagnostic Decision Support Systems (DDSS) but all move towards a common direction: provide assistance to the doctors/clinicians to make the right diagnosis for a specific patient, minimizing as much as possible the needed time for this. In doing so, some DDSS systems exploit existing crisp medical databases while others take an advantage of human knowledge and experience, by building fuzzy medical databases from scratch. It would be of interest though, as well as time saving, to combine these two together and examine how one can actually use an existing crisp medical dataset to transform it into a new fuzzy medical database with parameters being expressed and defined based on the clinicians' way of thinking. A methodology implementing this task is proposed in this paper accompanied by the results of its application on a real crisp medical database. PMID- 26152960 TI - A Decision Support System Platform for Spatial Epidemiology. AB - A wide range of health care systems have been implemented, to support medical opinions, which are defined as Decision Support Systems. In this work a pilot information system was developed based on patients health records data combined with Geographical Information Systems (GIS) technology, which could be used as an advisor in cases where epidemiological diseases are taking place. PMID- 26152961 TI - E-learning and Education. PMID- 26152962 TI - Open Innovation Challenge in Healthcare. Role for Education. AB - The vision of this paper is that collaboration creates new openings for engagement of non-commercial actors, such as universities, in innovation networks on the one hand, while opening up for collaborative innovation, and getting valuable real life anchors on the other hand, all these underpinned by greater connectivity and globalization. We present our approach in re-designing the courses on medical informatics and data processing to meet these challenges by employing public Internet services and media facilitation. PMID- 26152963 TI - Proactive Support of Internet Browsing when Searching for Relevant Health Information. AB - Many people use the Internet as one of the primary sources of health information. This is due to the high volume and easy access of freely available information regarding diseases, diagnoses and treatments. However, users may find it difficult to retrieve information which is easily understandable and does not require a deep medical background. In this paper, we present a new kind of Web browser add-on, in order to proactively support users when searching for relevant health information. Our add-on not only visualizes the understandability of displayed medical text but also provides further recommendations of Web pages which hold similar content but are potentially easier to comprehend. PMID- 26152964 TI - Benefits and Barriers of E-Learning for Staff Training in a Medical University. AB - Learning Management Systems (LMS) are a feasible solution to fulfill the various requirements for e-learning based training in a medical university. Using the LMS ILIAS, the Institute of Diagnostic and Interventional Radiology has designed an e learning unit about data protection, which has been used by 73% of the department's employees in the first three months. To increase the use of e learning for staff training, it is necessary to identify barriers and benefits, which encourage the use of e-learning. Therefore, we started an online survey to examine how the employees evaluate this learning opportunity. The results show that 87% of the employees had no technical problems and also competence of Information and Communication Technology (ICT) was no barrier. If anything, reported issues were time shortages and tight schedules. Therefore, short learning modules (less than 20 minutes) are preferred. Furthermore, temporal flexibility for learning is important for 83% of employees. PMID- 26152965 TI - West Midlands Health Informatics Network: A Perspective on Education and Training Needs. AB - The growth of health informatics as a discipline has led to an increase in networks of people with similar interests for discussion, learning and sharing. Alongside these community networks, education and training are gaining interest, with more career opportunities and general public seeking information. This paper highlights the experience of the West Midlands Health Informatics Network and efforts in better understanding the educational and training needs of its members. The findings from the survey conducted reveal that while the interest in this field is high among network members, the awareness of opportunities for training and learning professionally as well as personally, remains low. The areas and levels of interest in the region should help support the creation and availability of resources. PMID- 26152966 TI - Knowledge Management within the Medical University. AB - The aim of the work is studying the possibilities of ontological engineering in managing of medical knowledge. And also practical implementation of knowledge management system (KMS) in medical university. The educational process model is established that allows analyzing learning results within time scale. Glossary sub-system has been developed; ontologies of educational disciplines are constructed; environment for setup and solution of situational cases is established; ontological approach to assess competencies is developed. The possibilities of the system for solving situation tasks have been described. The approach to the evaluation of competence has been developed. PMID- 26152967 TI - Toward More Successful Biomedical Informatics Education Programs and Ecosystems in the Arab World. AB - Biomedical & Health Informatics (BMHI) is relatively new in Arab States. However, several programs/ tracks are running, with high promises of expansion. Programs are evaluated by national authorities, not by a specialized body/association. This does not always mean that the program is of an international standard. One of the possible ways of ensuring the quality of these programs is to be evaluated by international agencies. The International Medical Informatics Association (IMIA) has the expertise in the evaluation BMHI education programs. Accredited programs staffs will have the opportunities for Internationalization and to be engaged with other top-notch organizations, which will have great impacts on the overall implementations of the BMHI in the Arab World. The goal of this document is to show to Arab Universities (pilot: Egypt) how to apply for IMIA Accreditation for their programs. PMID- 26152968 TI - IMIA Dynamic Accreditation Procedure: Suggestions, Simplicity and Efficiency. AB - The International Medical Informatics Association (IMIA) is the world body for biomedical and health informatics (BMHI). IMIA accreditation program allows the health and medical informatics programs around the world to reach to an international level. Staffs (professors, students, education programmes directors, others) that work on the accredited BMHI programs will have the opportunity to be engaged with organizations that possess a world-class research and education profile from other countries, which will have great impacts on their field at their institutions, within their country providing the high quality overall health services. IMIA accreditation procedure is usually a long process and slightly complicated. The goal of this paper is to illustrate and to simplify the IMIA accreditation process to increase the success of the applicants. Toward more dynamic IMIA accreditation procedure, the paper presents 4 steps: translation, IMIA-Accreditation Step by Step Guideline, Questions and Answers, and finally the (new) Labelling System. PMID- 26152969 TI - Net Generation's Learning Styles in Nursing Education. AB - Numerous surveys have confirmed that emerging technologies and Web 2.0 tools have been a defining feature in the lives of current students, estimating that there is a fundamental shift in the way young people communicate, socialize and learn. Nursing students in higher education are characterized as digital literate with distinct traits which influence their learning styles. Millennials exhibit distinct learning preferences such as teamwork, experiential activities, structure, instant feedback and technology integration. Higher education institutions should be aware of the implications of the Net Generation coming to university and be prepared to meet their expectations and learning needs. PMID- 26152970 TI - An e-Learning Approach to Hospital Information Systems. AB - e-learning systems are advanced systems that are used to improve students learning capabilities as well as their accessibility by utilizing information and communication technology tools. The objective of this paper is to describe the methods which are used for the process of e-learning education in the program of distance learning at the National University of Athens for the course "Hospital Information Systems". These methods include the designing of the program, the development of the courses and the exercises and finally the availability of the courses to the students through the Rea education management system. The study also outlines the difficulties and the limitations occurred during the development of the program and suggests alternative options for future improvements. PMID- 26152971 TI - Health Professionals Information for Diagnostics Related Groups (DRGs) with the Use of a Website. AB - In recent years the costs of hospital care in developed countries absorbed a high proportion of total health resources. In Greece, after the establishment of the National Health System (NHS), funding for hospitals comes mainly from the state budget, and social insurance, therefore auditing of hospital cost is imperative to ensure their viability, especially at this time when the country is tested by economic crisis. Overtime many factors for the increase of hospital cost have been mentioned, such as the rapid development of medical technology, the low level of organization of the hospital system and the low productivity of human resources. The problem of rising health expenditure over the past decades is a worldwide phenomenon and it has brought about many changes in traditional retrospective methods for financing in the hospital sector, with prospective financial forms that combine patient composition and needs, and the productive activity of hospital need to the rationalization and contain expenditures. The system of Diagnosis Related Groups was a revolutionary success over the past decades and has now achieved worldwide recognition. PMID- 26152972 TI - Formalisation of Knowledge, Ontologies, Clinical Guidelines and Standards of Healthcare. PMID- 26152973 TI - Clinical Pathways: Identifying Development, Implementation and Evaluation Challenges. AB - Clinical pathways are comprehensive methods of planning, delivering and monitoring different healthcare services provided to patients. The main goal of using a clinical pathway is to build clinical decisions on medical evidence specific to each individual patient in addition to standardizing care provided to patients throughout different departments and healthcare services. At King Faisal Specialist Hospital and Research Center, Saudi Arabia, much effort has been done over the last few years to develop, implement and evaluate different clinical pathways and for years these efforts achieved less than expected success. The Health Information Technology Affairs (HITA) decided to analyze the challenges that we faced and should overcome by working on identifying these challenges and classifying them into the three main stages. The information about these challenges were both gathered from relevant departments, services and staff members as well as validated against published literature and research work. PMID- 26152974 TI - The Medical Ontology "HoPRO". AB - Current researches in health informatics provide the techniques and tools enabling the development of efficient hospital information ecosystem that can be made to exchange data with each other and thus provide a coherent patient oriented environment. In order to achieve this desired HIS interoperability, it is important to provide a clear understanding of the HIS ecosystem during the analysis phase that will provide the infrastructure of this ecosystem and lead to the development of systems that will be able to correspond with each other. Such an ontology is described here and its value will be demonstrated through a case study. PMID- 26152975 TI - Data Warehouse Design from HL7 Clinical Document Architecture Schema. AB - This paper proposes a semi-automatic approach to extract clinical information structured in a HL7 Clinical Document Architecture (CDA) and transform it in a data warehouse dimensional model schema. It is based on a conceptual framework published in a previous work that maps the dimensional model primitives with CDA elements. Its feasibility is demonstrated providing a case study based on the analysis of vital signs gathered during laboratory tests. PMID- 26152976 TI - Health Informatics. PMID- 26152977 TI - Innovative Information Systems in the Intensive Care Unit, King Saud Medical City in Saudi Arabia. AB - The purpose of this paper is to discuss the experience of implementing innovative information technology to improve the quality of services in one of the largest Intensive Care Units in Saudi Arabia. The Intensive Care Units in King Saud Medical City (ICU-KSMC) is the main ICU in the kingdom that represents the Ministry of Health. KSMC's ICU is also considered one of the largest ICU in the world as it consists of six units with 129 beds. Leaders in KSMC's ICU have introduced and integrated three information technologies to produce powerful, accurate, and timely information systems to overcome the challenges of the ICU nature and improve the quality of service to ensure patients' safety. By 2015, ICU in KSMC has noticed a remarkable improvement in: beds' occupation and utilization, staff communication, reduced medical errors, and improved departmental work flow, which created a healthy professional work environment. Yet, ICU in KSMC has ongoing improvement projects that include future plans for more innovative information technologies' implementation in the department. PMID- 26152978 TI - A Proposed Framework to Enrich Norwegian EHR System with Health-trusted Information for Patients and Professionals. AB - In the era of social media, semantic web and big data, a huge amount of health related information, knowledge and resources exist on the Web. Patients and healthcare professionals should spend enormous effort and time in order to find health-trusted information, while the appropriate technologies to interlink and retrieve this type of information already exist. In this paper we propose a framework to enrich DIPS, the most deployed Norwegian EHR System, with health trusted information for patients and state-of-the-art resources for healthcare professionals. The framework based upon the new architecture of DIPS, namely DIPS Arena, and upon the interlinking with the semantic web, social media and open linked data cloud information, knowledge and resources through well-established medical thesauri like SNOMED CT and MeSH. PMID- 26152979 TI - eHealth Services for the European Reference Network on Rare Anaemias (eENERCA). AB - This paper presents an electronic registry system for the purposes of the eENERCA for rare congenital conditions that require lifelong follow up and treatment. The main objective of the eENERCA project focusses on the prevention of major rare anaemias (RAs) by facilitating the access, at a European level, to the best genetic counselling, diagnosis and clinical management of the patients with RA independently of their country of origin. This can be achieved by promoting an extension of the full Electronic Health Record system and specifically the electronic registries for RAs, across Europe for the purposes stated hence promoting service development for the benefit of patients. The proposed eRegistry will serve as an epidemiological tool to improve the management of patient services and ultimately improve patient care. PMID- 26152980 TI - Serious Games for Home-based Stroke Rehabilitation. AB - On average, two thousand residents in the United States experience a stroke every day. These circumstances account for $28 billion direct costs annually and given the latest predictions, these costs will more than triple by 2030. In our research, we propose a portfolio of serious games for home-based stroke rehabilitation. The objective of the game approach is to enrich the training experience and establish a higher level of compliance to prescribed exercises, while maintaining a supportive training environment as found in common therapy sessions. Our system provides a collection of mini games based on rehabilitation exercises used in conventional physical therapy, monitors the patient's performance while exercising and provides clinicians with an interface to personalize the training. The clinician can set the current state of rehabilitation and change the playable games over time to drive diversification. While the system still has to be evaluated, an early stage case study with one patient offered positive indications towards this concept. PMID- 26152982 TI - Health Information Management. PMID- 26152981 TI - Assessing Greek Public Hospitals' Websites. AB - Following a previous (2011) survey, this study assesses the web pages of Greek public hospitals according to specific criteria, which are included in the same web page evaluation model. Our purpose is to demonstrate the evolution of hospitals' web pages and document e-health applications trends. Using descriptive methods we found that public hospitals have made significant steps towards establishing and improving their web presence but there is still a lot of work that needs to be carried out in order to take advantage of the benefits of new technologies in the e-health ecosystem. PMID- 26152983 TI - Developing an Emergency Physician Productivity Index Using Descriptive Health Analytics. AB - Emergency department (ED) crowding became a major barrier to receiving timely emergency care. At King Faisal Specialist Hospital and Research Center, Saudi Arabia, we identified variables and factors affecting crowding and performance to develop indicators to help evaluation and improvement. Measuring efficiency of work and activity of throughput processes; it was important to develop an ED physician productivity index. Data on all ED patients' encounters over the last six months of 2014 were retrieved and descriptive health analytics methods were used. Three variables were identified for their influence on productivity and performance; Number of Treated Patients per Physician, Patient Acuity Level and Treatment Time. The study suggested a formula to calculate the productivity index of each physician through dividing the Number of Treated Patients by Patient Acuity Level squared and Treatment Time to identify physicians with low productivity index and investigate causes and factors. PMID- 26152984 TI - Real-Time Classification of Exercise Exertion Levels Using Discriminant Analysis of HRV Data. AB - Heart rate variability (HRV) was shown to reflect activation of sympathetic nervous system however it is not clear which set of HRV parameters is optimal for real-time classification of exercise exertion levels. There is no studies that compared potential of two types of HRV parameters (time-domain and frequency domain) in predicting exercise exertion level using discriminant analysis. The main goal of this study was to compare potential of HRV time-domain parameters versus HRV frequency-domain parameters in classifying exercise exertion level. Rest, exercise, and recovery categories were used in classification models. Overall 79.5% classification agreement by the time-domain parameters as compared to overall 52.8% classification agreement by frequency-domain parameters demonstrated that the time-domain parameters had higher potential in classifying exercise exertion levels. PMID- 26152985 TI - Taming Big Data: An Information Extraction Strategy for Large Clinical Text Corpora. AB - Concepts of interest for clinical and research purposes are not uniformly distributed in clinical text available in electronic medical records. The purpose of our study was to identify filtering techniques to select 'high yield' documents for increased efficacy and throughput. Using two large corpora of clinical text, we demonstrate the identification of 'high yield' document sets in two unrelated domains: homelessness and indwelling urinary catheters. For homelessness, the high yield set includes homeless program and social work notes. For urinary catheters, concepts were more prevalent in notes from hospitalized patients; nursing notes accounted for a majority of the high yield set. This filtering will enable customization and refining of information extraction pipelines to facilitate extraction of relevant concepts for clinical decision support and other uses. PMID- 26152986 TI - Nora: A Vocabulary Discovery Tool for Concept Extraction. AB - Coverage of terms in domain-specific terminologies and ontologies is often limited in controlled medical vocabularies. Creating and augmenting such terminologies is resource intensive. We developed Nora as an interactive tool to discover terminology from text corpora; the output can then be employed to refine and enhance natural language processing-based concept extraction tasks. Nora provides a visualization of chains of words foraged from word frequency indexes from a text corpus. Domain experts direct and curate chains that contain relevant terms, which are further curated to identify lexical variants. A test of Nora demonstrated an increase of a domain lexicon in homelessness and related psychosocial factors by 38%, yielding an additional 10% extracted concepts. PMID- 26152987 TI - Developing an Institutional Repository of Digital Health Information Content. AB - Over the past few years, the use of electronic sources for studies by students and teaching staff has been rapidly increased. The digital information gives the opportunity of personal and interactive information. Nevertheless, much of health information is unable to be identified from existing search tools. The aim of this paper is to propose a system which enables academic members of the Faculty of Nursing of the University of Athens to immediate access information that improves patient care and the daily nursing practice. First of all, in order to achieve this goal, an on-line research was conducted on Science Direct, Scopus, PubMed and Google Scholar. Afterwards, the appropriate digital library software package was selected. This work presents the institutional repository "Ariadne". This repository is a new service which intends to establish new conditions to archiving of graduate and doctoral dissertations. The "Ariadne" repository is not just a tool for strengthening the educational process but also a tool for further progress of nursing science. PMID- 26152988 TI - Integrated Electronic Health Record Database Management System: A Proposal. AB - eHealth has attained significant importance as a new mechanism for health management and medical practice. However, the technological growth of eHealth is still limited by technical expertise needed to develop appropriate products. Researchers are constantly in a process of developing and testing new software for building and handling Clinical Medical Records, being renamed to Electronic Health Record (EHR) systems; EHRs take full advantage of the technological developments and at the same time provide increased diagnostic and treatment capabilities to doctors. A step to be considered for facilitating this aim is to involve more actively the doctor in building the fundamental steps for creating the EHR system and database. A global clinical patient record database management system can be electronically created by simulating real life medical practice health record taking and utilizing, analyzing the recorded parameters. This proposed approach demonstrates the effective implementation of a universal classic medical record in electronic form, a procedure by which, clinicians are led to utilize algorithms and intelligent systems for their differential diagnosis, final diagnosis and treatment strategies. PMID- 26152989 TI - Healthcare IT. PMID- 26152990 TI - Multiprocessor Neural Network in Healthcare. AB - A possible way of creating a multiprocessor artificial neural network is by the use of microcontrollers. The RISC processors' high performance and the large number of I/O ports mean they are greatly suitable for creating such a system. During our research, we wanted to see if it is possible to efficiently create interaction between the artifical neural network and the natural nervous system. To achieve as much analogy to the living nervous system as possible, we created a frequency-modulated analog connection between the units. Our system is connected to the living nervous system through 128 microelectrodes. Two-way communication is provided through A/D transformation, which is even capable of testing psychopharmacons. The microcontroller-based analog artificial neural network can play a great role in medical singal processing, such as ECG, EEG etc. PMID- 26152991 TI - Understanding and De-risking the Dependencies between Operator and Manufacturer of Clinical IT. AB - Health IT, in addition to benefits can also have unintended consequences both in terms of operational and business risks. Understanding the dependencies between operator and manufacturer as well as issues that need to be addressed during procurement is essential to increase confidence in the operation of health IT. The paper provides the context, and a number of issues health IT operators such as clinical organisations, need to investigate during acquisition of health IT. PMID- 26152992 TI - AppFactLib - A Concept for Providing Transparent Information about Health Apps and Medical Apps. AB - Users often have to rely on incomplete or marketing oriented information sources when they have to decide whether they trust an app they are interested in or not since official quality seals are lacking. While various tools exist that aim at aiding users with assessing an app's quality, using them is often cumbersome; also, the available information is often insufficient for applying these tools and making an informed decision. Based on an approach we previously described, i.e. an app synopsis that aims at providing manufacturers of health apps and medical apps with a standardized and transparent method for providing information about their products, in the present paper, we now outline a concept for disseminating such information via an easy-to-use platform. PMID- 26152993 TI - Healthcare Management. PMID- 26152994 TI - Greece Financial Crisis and Quality of Life. AB - The last six years the global community is facing an economic crisis that first appeared in USA. This crisis has a lot of impacts especially in health sector. Unemployment, job insecurity and the loss of disposable income have a significant impact in health too. The main objective of this research was to investigate the quality of life of the general population in Greece during the financial crisis. To collect the data it has been used the Greek version of Short Form (36) Health Survey (SF-36v2). In general, income, level of education, cohabitation and parenthood had a significant impact in quality of life. As a conclusion, unemployed participants' score was lower in the entire dimensions and in the two summary scales too. PMID- 26152995 TI - The Empowerment of Patients with Mental Conditions and Addictions through e Health. AB - The aim of the current paper is the imparting of useful information to both patients and people in general regarding the development of mental conditions based on drug addictions, through e-health. It will provide all related information in order to achieve the empowerment of the selected sample regarding their conditions in terms of conceptualizing their health status. The general part is consisting of an overview on patient empowerment and e-health. The special part refers to the details of developing and presenting the above mentioned website. The information presented in the web site is addressing the general population and not only patients suffering a mental condition or addiction. The website contains the related articles and information obtained from the related bibliographical search. The main goal of the website is to impart concise information on the related issues. PMID- 26152996 TI - Staffing and Educational Level of Military Hospital Personnel in Relation to Patients' Satisfaction from the Provided Health Care Services. AB - Over the course of the last decades there has been a significant interest in assessing the quality of the health care services. Professionals and experts recognize patient satisfaction as an important indicator of the so-called quality. The purpose of the study is to measure patients' satisfaction in a military hospital in relation to educational and staffing levels of the health care workers. The evaluation in the individual level has been done by completing questionnaires. The study involved 109 patients from 2 clinics. According to the results, the majority of the patients indicated high satisfaction level both from physicians and nurses. The high educational level and general competence of the health care personnel are the key elements for the efficient provision of health care services. PMID- 26152997 TI - Mobile Technology in Healthcare. PMID- 26152998 TI - Do Ethics Need to be Adapted to mHealth? AB - Available codes of ethics do not always adequately address questions arising from the contingent use of new technologies. In medical and health related settings, this manifests itself in the context of mHealth projects, where often, devices not specifically designed for such purposes, e.g. smartphones, tablet PCs and similar devices and gadgets are employed with the hope of benefitting both patients as well as their caretakers and furthermore researchers. Still, the highly personal nature of health and medicine as well as technical "constant companions" that are nowadays firmly woven into almost everyone's daily life, require a closer look at ethical requirements in this subject area. Therefore, in this paper, we will first present a short overview of existing codes of ethics, scrutinize their applicability for mHealth related problems and present a guideline compiled from suitable points taken from them. PMID- 26152999 TI - A Systematic Review of Mobile Health Technology Use in Developing Countries. AB - In developing countries, patients are now more informed about their healthcare options as a result of their use of mobile health (mHealth) technologies. The purpose of this paper is to describe the opportunities and challenges in using mHealth technologies for developing countries. In April 2015, Google Scholar and PubMed were searched to identify articles discussing the types, advantages and disadvantages, effectiveness, evaluation of mHealth technologies, and examples of mHealth implementation in developing countries. A total number of 3,803 articles were retrieved from both databases. Articles reporting the benefits and risks, effectiveness, and evaluation of mHealth were included. Articles that were written in English and from developing countries were also included. We excluded papers that were published before 2005, not written in English, and that were technical in nature. After screening the articles using the inclusion and exclusion criteria, 27 articles were selected for inclusion in the study. Of the 27 papers included in the review, eight described opportunities and challenges relating to mHealth, four focused on smoking cessation, three focused on weight loss, and four papers focused on chronic diseases. We also identified four articles discussing mHealth evaluation and four discussing the use of mHealth as a health promotion tool. We conclude that mHealth can improve healthcare delivery for developing countries. Some of the advantages of mHealth include: patient education, health promotion, disease self-management, decrease in healthcare costs, and remote monitoring of patients. However, there are several limitations in using mHealth technologies for developing countries, which include: interoperability, lack of evaluation standards, and lack of a technology infrastructure. PMID- 26153000 TI - The "SMART Travel Health" Mobile Application Assessment. AB - An empirical study was conducted to evaluate the users' perception on a pilot mobile application ("SMART Travel Health"), their attitude towards use, and their intention to use it. A theoretical model was constructed based on TAM and other related works. The population was 88 travellers who used the pilot application. Data analysis was performed using partial least squares path modeling. Results highlight the very strong significant effect of perceived ease of use to perceived usefulness, the strong significant effect of perceived usefulness to attitude towards use, as well as, the significant effect of perceived ease of use to attitude towards using the application. Also, the strong significant effect of attitude towards use to behavioral intention to use is presenting the positive perception of the population about this mobile application. PMID- 26153001 TI - Public Health Informatics. PMID- 26153002 TI - eHealth in Saudi Arabia: Current Trends, Challenges and Recommendations. AB - The purpose of this study is to explore the current status of eHealth in Saudi Arabia from the perspective of health informatics professionals. We used a case study approach and analyzed participant data using thematic analysis. The study took place between July and August 2013. Data collection included interviews with nine senior health information professionals in Saudi Arabia. The findings describe participant views on current eHealth trends in Saudi Arabia and show differences among Saudi healthcare organizations in terms of eHealth adoption. Participants also describe the challenges relating to organizational and cultural issues, end user attitudes towards eHealth projects, and the lack of specialized human resources to implement eHealth systems. Two main recommendations made by the participants were to form a new national body for eHealth and to develop a unified plan for the implementation of Saudi eHealth initiatives. PMID- 26153003 TI - Building a Culture of Health Informatics Innovation and Entrepreneurship: A New Frontier. AB - Entrepreneurship and innovation within the health informatics (HI) scientific community are relatively sluggish when compared to other disciplines such as computer science and engineering. Healthcare in general, and specifically, the health informatics scientific community needs to embrace more innovative and entrepreneurial practices. In this paper, we explore the concepts of innovation and entrepreneurship as they apply to the health informatics scientific community. We also outline several strategies to improve the culture of innovation and entrepreneurship within the health informatics scientific community such as: (I) incorporating innovation and entrepreneurship in health informatics education; (II) creating strong linkages with industry and healthcare organizations; (III) supporting national health innovation and entrepreneurship competitions; (IV) creating a culture of innovation and entrepreneurship within healthcare organizations; (V) developing health informatics policies that support innovation and entrepreneurship based on internationally recognized standards; and (VI) develop an health informatics entrepreneurship ecosystem. With these changes, we conclude that embracing health innovation and entrepreneurship may be more readily accepted over the long-term within the health informatics scientific community. PMID- 26153004 TI - Social Media and Health. PMID- 26153005 TI - #DigitalHealth: Exploring Users' Perspectives through Social Media Analysis. AB - In order to explore the role of social media in forming an understanding of digital healthcare, we conducted a study involving sentiment and network analysis of Twitter contents. In doing this, we gathered 20,400 tweets that mentioned the key term #DigitalHealth for 55 hours, over a three-day period. In addition to examining users' opinions through sentiment analysis, we calculated in-degree centralities of nodes to identify the hubs in the network of interactions. The results suggest that the overall opinion about digital healthcare is generally positive. Additionally, our findings indicate that the most prevalent keywords, associated with digital health, widely range from mobile health to wearable technologies and big data. Surprisingly, the results show that the newly announced wearable technologies could occupy the majority of discussions. PMID- 26153006 TI - A Social Media Campaign to Promote Breastfeeding among Saudi Women: A Web-based Survey Study. AB - Prolonged breastfeeding can prevent or limit the severity of a variety of diseases and conditions. Although evidence clearly shows that there are health benefits for breastfeeding, adherence to breastfeeding remains a key challenge facing maternal health providers in Saudi Arabia. The purpose of this study is to evaluate the impacts of a social media platform (Twitter) to promote breastfeeding in Saudi Arabia. Between February 10 and March 25, 2015, a web based questionnaire was administered to evaluate the impacts of a Twitter based educational campaign on the awareness, knowledge, and adherence to breastfeeding behavior for women in Saudi Arabia. The overall response rate among mothers with a newborn child was 83% (n=484). The results showed an increase in the knowledge and awareness of breastfeeding practices and adherence among Twitter followers. The initiation rate of breastfeeding had slightly increased among women who never had previously breastfed. More women reported their willingness to continue exclusive breastfeeding and to stop bottle-feeding. Results also show that an integration of professional breastfeeding support, public health education programs through social media could be an effective tool in promoting breastfeeding in Saudi Arabia. There is a need for further research on designing and implementing a social media based educational outreach program to increase women's awareness, knowledge, and adherence to breastfeeding behavior in Saudi Arabia. PMID- 26153008 TI - Facebook and Health Information: Content Analysis of Groups Related to Schizophrenia. AB - Facebook Groups is a space for connecting people with common interests. People with a psychiatric diagnosis use social networking sites. However Facebook Groups related to schizophrenia have not been investigated before. We aimed to examine Facebook Groups related to schizophrenia. Deductive content analysis was applied. Out of the included groups (N=32), the majority's principal objective was awareness creation (n=11, 34%) and support to those with schizophrenia and their caregivers (n=9, 28%). Monitoring the Facebook Groups' content related to schizophrenia and other mental disorders is essential, since it could be an important communication and support platform for people with the disorder and their caregivers. PMID- 26153007 TI - Exploring the Role of Twitter in Promoting Women's Health in the Arab World: Lessons Learned. AB - Women's health is a topic that has been largely overlooked within the Arab world. Nevertheless, the constant growth in the use of social media provides an opportunity to improve women's health in the Arab world. In this paper, we discuss our experiences and lessons learned with the development of a women's health promotional campaign in the Arabic language using Twitter, a popular social media platform in the Arab world. We analyzed the combined experiences of five researchers in the development of the Twitter account. Two separate meetings were held, one on March 10 and another on March 25, 2015 with the researchers to review their experiences and lessons learned in developing a Twitter health promotion platform for women's health in the Arab world. The shared experiences were thematically transcribed, coded, matched and grouped under six key themes identified as the main driving forces for the development of a successful health promotion Twitter account. We found that the success of the Twitter account was the result of: defining clear goals, being passionate about the health promotion campaign, being motivated and creative, being knowledgeable about the health promotion area, developing trust between Twitter accounts users and the healthcare provider, and being patient in communicating with Twitter account users. Future research needs to focus on a more detailed analysis of the twitter feeds shared between the users and the health practitioners which can enhance our understanding of the social media based public health educational interventions. PMID- 26153009 TI - The Role of Social Media in Promoting Women's Health Education in Saudi Arabia. AB - Social media has the potential to improve women's health in developing countries through health education and promotion. In the Arab world, women's health interventions are lacking. However, with a high penetration rate of social media in the Arab world, there is good opportunity to utilize social media platforms such as Twitter to promote women's health. In this paper, we analyze the Tweet feeds of Saudi-based Twitter account to promote women's health. A total of 5167 Tweets were extracted and analyzed retrospectively, using NVivo Ncapture between June 2014 and March 2015. There were a total number of 3449 followers by March 20, 2015. Results showed that a majority of the Twitter followers (61%, n=2104) were seeking gynecological information, followed by pregnancy related information (27%, n=931), breast-feeding advice (9%, n=310), and other health related information (3%, n=103). Results also showed an increased level of health awareness and comprehension among Twitter followers. Further research is needed to promote women's health in Saudi Arabia and the Arab world through social media platforms such as Twitter and similar platforms including Instagram, Facebook, and YouTube which are also popular in the Arab world. PMID- 26153010 TI - The Prevalence of Using Social Media among Healthcare Professionals in Saudi Arabia: A Pilot Study. AB - Keeping up-to-date with new health information is a necessity for healthcare professionals. Today, social media platforms such as Twitter, among others, are important sources for healthcare professionals. Within the Arab world, little is known about how healthcare professionals use social media to update their healthcare information. This study aims to estimate the prevalence of healthcare professionals, primarily physicians, in seeking online health information in Saudi Arabia. We conducted a web-based survey among Twitter participants between February 1 and March 10, 2015. The primary outcome measures were the self reported rates of Twitter use, perceived effects, and the influence of Twitter information on clinical practice. Our results revealed that the prevalence rate of physician's seeking online health information was 79% (n=166); the majority of them (71.4%, n=150) reported that Twitter had a significant impact in increasing their medical knowledge and in improving their clinical practice. Over half of the survey participates reported the need for investment in establishing trustworthy and credible health Twitter accounts. The participants reported that their preference for social media health accounts that focus on women's health, non-communicable disease and psychotherapy (20%, 18.1% and 14.5% respectively). The findings showed clearly that seeking web-based medical information through social media is popular among physicians, in general, but especially among younger physicians in Saudi Arabia. The study findings indicate to the necessity for further research on designing and implementing a national social media based educational outreach program to provide evidence-based healthcare information and improve healthcare providers' knowledge and skills in Saudi Arabia. PMID- 26153011 TI - Social Networks and Health. AB - Nowadays the social networks have been developed into an advanced communications tool, which is important for all people to contact each other. These specific networks do offer lots of options as well as plenty of advantages and disadvantages. The social websites are many in number and titles, such as the facebook, the twitter, the bandoo etc. One of the most important function mechanisms for the social network websites, are the marketing tools. The future goal is suggested to be the evolution of these programs. The development of these applications, which is going to lead into a new era for the social digital communication between the internet users, all around the globe. PMID- 26153012 TI - Telemedicine. PMID- 26153013 TI - Resilient Systemics to Telehealth Support for Clinical Psychiatry and Psychology. AB - Reliably expanding our clinical practice and lowering our overhead with telepsychiatry, telepsychology, distance counseling and online therapy, requires resilient and antifragile system and tools. When utilized appropriately these technologies may provide greater access to needed services to include more reliable treatment, consultation, supervision, and training. The wise and proper use of technology is fundamental to create and boost outstanding social results. We present, as an example, the main steps to achieve application resilience and antifragility at system level, for diagnostic and therapeutic telepractice and telehealth support, devoted to psychiatry and psychology application. This article presents a number of innovations that can take psychotherapy treatment, supervision, training, and research forward, towards increased effectiveness application. PMID- 26153014 TI - Towards Resilient Telehealth Support for Clinical Psychiatry and Psychology: A Strategic Review. AB - Human beings have increasingly shown a willingness to adopt Internet, mHealth and telehealth applications as a part of managing their health. Recent technological advances in the use of the Internet and video technologies has greatly impacted the provision of psychotherapy and other clinical services as well as how the training of psychotherapists may be conducted. When utilized appropriately these technologies may provide greater access to needed services to include treatment, consultation, supervision, and training. The major issue in such a development is whether online interventions will be structured or unstructured. The proper use of technology is fundamental to create and boost outstanding results. We present a strategic review and, as an example, the main steps to develop and achieve application resilience and antifragility at system level, for diagnostic and therapeutic telepractice and telehealth support. This article presents a number of innovations that can take psychotherapy treatment, supervision, training, and research forward, towards increased effectiveness application. PMID- 26153015 TI - Ontology-based Medical Decision Support System to Enhance Chronic Patients' Lifestyle within E-care Telemonitoring Platform. AB - The aim of this paper is to describe an original approach which consists of designing ontology based Medical Decision Support System (MDSS) to enhance the patients' lifestyle. This system is composed of two main parts: data collector which collects relevant lifestyle-related patent data by prompting the only significant questions in connection with the patient's medical background, and advices provider which provides personalized lifestyle advices to the patients regarding their lifestyle changes. The proposed MDSS is integrated within E-care home health monitoring platform in order to: (i) improve the patient's healthy lifestyle; (ii) educate the patients towards their disease; (iii) increase the early detection of risky situation. PMID- 26153016 TI - iSignIT - Communication App and Concept for the Deaf and Hard of Hearing. AB - In medical settings, those who are deaf or hard of hearing and have to rely on sign language are often at a disadvantage when they want to communicate with doctors or other caretakers. Professional translators are not always available. To alleviate the problems, a mobile phrasebook for communication between affected patients and their caretakers was designed and implemented in form of the iSignIT app. All of the phrases it contains are also available as videos recorded from native speakers of sign language. Based on the positive feedback received so far, we are now in the process of taking further steps to ensure continuing development and obtaining sustainable financing of the project; here, we will outline some of the steps to be taken. PMID- 26153017 TI - The Digital Microscopy in Organ Transplantation: Ergonomics of the Tele Pathological Evaluation of Renal and Liver Grafts. AB - AIM: Ergonomics of Digital Microscopy (DM) based on virtual slides, on Telemedicine Systems (TS) for Tele-Pathological (TPE) evaluation of the grafts (G) in organ transplantation (OT). MATERIAL AND METHODS: Simulation of DM on TS based TPE by 2 specialists on a total of 238 human Renal Graft (RG) and 172 Liver Graft (LG) tissues digital microscopic images diagnosing inflammatory and neoplastic lesions on four different electronic spaces (ES). RESULTS: DM on TS for TPE in OT is elaborated perfectly on the ES of a Desktop, followed by the ES of the applied Exp.-TS. Tablet and Mobile-Phone ES seem significantly risky for the application of DM in OT (p<.001). CONCLUSION: Integration of DM on TS for TPE is feasible, while ergonomics of post-grafting and pre-transplant decision support and planning depend on the size of the working ES. PMID- 26153018 TI - Health Professionals' Use of Computer Databases to Utilize Research for Practice: A Pilot Study. AB - Factors associated with information retrieval have been tested in the present pilot project, suggested an appropriate instrument chosen from previous research. The purpose of this paper is to access the internal validity and the internal consistency reliability of the research instrument. The questionnaire determine the information needs, information seeking behavior, the adequacy of online information sources, examine access, training received, barriers in using information technology and research utilization. The pilot questionnaire was distributed to nurses and physicians working in Greek hospitals and was tested for its validity and reliability coefficients. PMID- 26153022 TI - Molecular and Histological Association Between Candida albicans from Oral Soft Tissue and Carious Dentine of HIV-Positive Children. AB - Candida albicans and caries are frequently investigated among healthy and immunosuppressed individuals. The objective of this study was to demonstrate the presence of C. albicans on both oral soft and hard tissue and to investigate, at molecular level, the genetic subtype of the organism from the two oral sites. Tongue swabs and dentine scrapings from 362 HIV-positive children, referred for the extraction of carious primary teeth, were cultured on CHROMagar and identified to species level with ID32C. Histological staining of extracted carious teeth was also done. In patients with positive C. albicans cultures from both the tongue and carious dentine, DNA fingerprinting of such paired isolates was performed, using Southern blot hybridisation with the Ca3 probe. Yeasts were cultured from the tongue of 151 (41.7 %) individuals and 57 (37.7 %) simultaneously yielded positive C. albicans cultures from carious dentine. Nine different yeast spp. were identified from the tongue using the ID32C commercial system, but C. albicans was the only species recovered from carious dentine and histological investigation demonstrated fungal elements penetrated into the dentine and not limited to superficial debris on the floor of the cavity. Twelve of 13 paired isolates of C. albicans revealed identical fingerprinting patterns. The findings from this study demonstrated that in a particular individual, the same genetic subtype of C. albicans was capable of colonising both oral soft tissue and carious dentine. This renders carious teeth a constant source, or reservoir, of potentially infectious agents and, particularly among immunosuppressed individuals, should therefore not be left unattended. PMID- 26153024 TI - Response to "Characteristics of 2p15-p16.1 microdeletion syndrome: review and description of two additional patients". PMID- 26153023 TI - Artesunate induces ROS- and p38 MAPK-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells. AB - Rhabdomyosarcoma represents about 50% of soft-tissue sarcomas and 10% of malignant solid tumors in childhood. Embryonal rhabdomyosarcoma (ERMS) is the most frequent subtype, suggested to have an origin in muscle precursor cells that fail to exit the cell cycle and terminally differentiate mainly because of overexpression of the transcription factor, PAX7, which sustains proliferation, migration and invasiveness in ERMS cells. Artesunate (ARS) is a semi-synthetic derivative of artemisinin (ART), a natural compound well known as an antimalarial drug. However, ART and its derivatives have been found efficacious even as anticancer drugs that induce cell cycle arrest and/or apoptosis in several kinds of cancer. Here, we show that ARS dose-dependently induces DNA damage and apoptosis in ERMS cell lines. Production of reactive oxygen species (ROS) and activation of p38 MAPK have a central role in triggering ARS-mediated apoptosis in ERMS cells; indeed either the antioxidant, N-acetylcysteine or the p38 MAPK inhibitor, SB203580, protects ERMS cells from ARS-induced apoptosis. Moreover, ARS treatment in ERMS cells ROS-dependently induces the expression of the myo miRs, miR-133a and miR-206, which are down-regulated in RMS, and reduces PAX7 protein levels. Finally, ARS upregulates the expression of the adhesion molecules, NCAM and integrin beta1, and reduces migration and invasiveness of ERMS cells in vitro, and ARS treatment reduces of about 50% the growth of ERMS xenografts in vivo. Our results are the first evidence of efficacy of ART derivatives in restraining ERMS growth in vivo, and suggest ARS as a potential candidate for therapeutic treatment of ERMS. PMID- 26153026 TI - ISPAD Clinical Practice Consensus Guidelines 2014 Compendium: Type 2 diabetes in the child and adolescent. PMID- 26153025 TI - Active Acetylcholinesterase Immobilization on a Functionalized Silicon Surface. AB - In this work, we studied the attachment of active acetylcholinesterase (AChE) enzyme on a silicon substrate as a potential biomarker for the detection of organophosphorous (OP) pesticides. A multistep functionalization strategy was developed on a crystalline silicon surface: a carboxylic acid-terminated monolayer was grafted onto a hydrogen-terminated silicon surface by photochemical hydrosilylation, and then AChE was covalently attached through amide bonds using an activation EDC/NHS process. Each step of the modification was quantitatively characterized by ex-situ Fourier transform infrared spectroscopy in attenuated total-reflection geometry (ATR-FTIR) and atomic force microscopy (AFM). The kinetics of enzyme immobilization was investigated using in situ real-time infrared spectroscopy. The enzymatic activity of immobilized acetylcholinesterase enzymes was determined with a colorimetric test. The surface concentration of active AChE was estimated to be Gamma = 1.72 * 10(10) cm(-2). PMID- 26153027 TI - Emphysematous Cystitis. PMID- 26153028 TI - Urgent Thyroid-Stimulating Hormone Testing in Emergency Medicine: A Useful Tool? AB - BACKGROUND: Thyroid-stimulating hormone (TSH) has recently been introduced among the tests available to the Emergency Department (ED) of our hospital. OBJECTIVE: To evaluate the prevalence of TSH-level-dependent thyroid dysfunction and to assess the usefulness of urgent TSH testing in a series of emergency patients. METHODS: We planned a single-center observational cross-sectional clinical study. We divided patients in groups according to their thyroid status using defined TSH decision levels. Previously diagnosed history of thyroid dysfunction and newly diagnosed thyroid dysfunctions were differentiated. Further, we analyzed the subset of emergency patients affected by atrial fibrillation (AF) due to the role of hyperthyroidism in AF pathogenesis. For each TSH request, we made a retrospective chart review to assess the usefulness of the test based on clinical efficacy and management efficiency indicators. RESULTS: The present study showed that, although the overall thyroid dysfunction rate was higher than in the general population, only a few newly diagnosed thyroid dysfunctions were found with limited clinical utility. We categorized urgent TSH requests as useful and not useful, by retrospective evaluation, and we identified and compared the main TSH testing clinical indications in the two groups. CONCLUSION: We found a positive impact of urgent TSH determination in emergency decision-making. Nevertheless, a stronger clinical impact could be achieved by improving request appropriateness and by targeting TSH testing to some clinical indications identified by the study. The work was considered a quality-improvement project by the Hospital Committee for Quality Management. PMID- 26153029 TI - Myofascial Pain Syndromes in the Emergency Department: What Are We Missing? AB - BACKGROUND: Myofascial pain syndrome (MPS), pain originating in the myofascial tissue, is a widely recognized pathology characterized by the presence of referred pain (often distant from its origin and specific to each muscle) that can resemble other pathologies and by the presence of a trigger point, a localized hyperirritable band able to reproduce the pain and its associated symptoms. Patients with acute or chronic MPS are commonly seen in the emergency department (ED), usually complaining of pain of undetermined origin. Traditionally, the emergency physician (EP) is not trained to diagnose and treat MPS, and many patients with MPS have received less than optimal management of this condition in the ED. Many types of treatments are known to be effective against MPS. Among these, trigger point injection (TPI) is considered a practical and rapid approach that can be carried out in the ED by EPs. OBJECTIVE: This article reviews the current diagnostic methods, treatment options, and procedures for MPS patients seen in the ED to enable EPs to diagnose and successfully treat this condition. DISCUSSION: This article discusses the clinical characteristics, etiology, diagnosis, and treatment of MPS in the ED, including a description of performing TPI. CONCLUSIONS: MPS can mimic other clinical conditions commonly seen in the ED. MPS can be diagnosed on the basis of clinical findings; in many cases, no imaging or laboratory testing is needed. Therefore, MPS diagnosis and treatment can be successfully accomplished in the ED by EPs. PMID- 26153030 TI - Weapons Retrieved After the Implementation of Emergency Department Metal Detection. AB - BACKGROUND: Several high-profile violent incidents have occurred within emergency departments (EDs). There are no recent studies reporting the effectiveness of ED metal detection. OBJECTIVE: Our aim was to assess the effect of metal detection on ED weapons retrieval. METHODS: In September 2011, a metal detector was installed at the entrance of an urban, high-volume teaching hospital ED. The security company recorded retrieved firearms, knives, chemical sprays, and other weapons. We performed qualitative analysis of weapons retrieval data for a 26 month period. RESULTS: A total of 5877 weapons were retrieved, an average of 218 per month: 268 firearms, 4842 knives, 512 chemical sprays, and 275 other weapons, such as brass knuckles, stun guns, and box cutters. The number of retrieved guns decreased from 2012 to 2013 (from 182 to 47), despite an increase in metal detection hours from 8 h per day to 16 h per day. The number of retrieved knives, chemical sprays, and other weapons increased. Recovered knives increased from 2062 in 2012 to 2222 in 2013, chemical sprays increased from 170 to 305, and other weapons increased from 51 to 201. CONCLUSIONS: A large number of weapons were retrieved after the initiation of metal detection in the ED entrance. Increasing hours of metal detection increased the number of retrieved knives, chemical sprays, and other weapons. Retrieved firearms decreased after increasing metal detection hours. Metal detection in the ED entrance is effective in reducing entrance of weapons into the ED. Metal detectors may offer additional benefit in reducing attempts to enter with firearms. PMID- 26153031 TI - Bronchoscopic Findings Associated with Inhaled Chlorine Toxicity. PMID- 26153032 TI - Obstructive Wharton Duct Sialadenitis. PMID- 26153033 TI - Retroperitoneal Hematoma After Femoral Arterial Catheterization. PMID- 26153034 TI - Significance of calcium-sensing receptor expression in gastric cancer. AB - OBJECTIVE: The calcium-sensing receptor (CaSR) is known to have differential expression in various carcinomas and normal tissues. It has been shown to be involved in carcinogenesis or tumor suppression. However, its role in gastric cancer remains unknown. This study was performed to determine the CaSR expression level in gastric cancer and non-tumor gastric tissues and to examine the related clinicopathological factors. MATERIALS AND METHODS: Thirty-one pairs of gastric cancer tissues and matched non-tumor gastric tissues were obtained from surgical tissues after gastrectomy. Using real-time polymerase chain reaction, we measured CaSR mRNA expression. We evaluated the association between CaSR mRNA expression and clinicopathological variables based on the downregulation or upregulation of CaSR mRNA expression in gastric cancer tissues compared to those of matched non tumor gastric tissues. By immunohistochemistry, we confirmed CaSR expression levels in gastric cancer tissues. RESULTS: Downregulation of CaSR mRNA was observed in 77.4% of gastric cancer tissues compared to their matched normal tissues. Downregulated CaSR was associated with a tendency for deeper invasion into the proper muscle (p = 0.028) and more advanced stage (II-IV; p = 0.012). CONCLUSION: We conclude that downregulation of CaSR may contribute to the prevention or suppression of tumor outgrowth. PMID- 26153035 TI - Nondestructive Speciation Depth Profiling of Complex TiOx Nanolayer Structures by Grazing Incidence X-ray Fluorescence Analysis and Near Edge X-ray Absorption Fine Structure Spectroscopy. AB - An important challenge of modern material science is the depth-sensitive and nondestructive analysis of the chemical binding state of complex structures consisting of multiple thin layers. In general, the correlation of the material functionality and underlying chemical and physical properties is the key question in view of directed device development, performance, and quality control. It has been shown that the combined method grazing incidence X-ray fluorescence analysis (GIXRF) and near edge X-ray absorption fine structure spectroscopy (NEXAFS) can significantly contribute to the nondestructive chemical analysis of buried thin films and interface structures regarding chemical speciation. Recently, we have enhanced the method to allow for a depth-resolved analysis of multilayered nanoscaled thin film structures. By means of appropriate model systems, the methodology has been developed and successfully validated. The model systems basically consist of a carbon cap layer, two titanium layers differing in their oxidation states and separated by a thin carbon layer, and a silicon substrate covered with molybdenum and a carbon layer. A differential approach has been developed to derive the chemical species of each of the titanium layers. PMID- 26153036 TI - Biological effects and toxicity of diluted bitumen and its constituents in freshwater systems. AB - Approximately 50 billion cubic meters of bitumen resides within the oil sands region of Alberta, Canada. To facilitate the transport of bitumen from where it is extracted to where it is processed, the bitumen is diluted with natural gas condensate ('dilbit'), synthetic crude from hydrocracking bitumen ('synbit'), or a mixture of both ('dilsynbit'). A primary consideration for the effects of diluted bitumen products on freshwater organisms and ecosystems is whether it will float on the water surface or sink and interact with the stream or lake sediments. Evidence from a spill near Kalamazoo, MI, in 2010 and laboratory testing demonstrate that the nature of the spill and weathering of the dilbit, synbit or dilsynbit prior to and during contact with water will dictate whether the product floats or sinks. Subsequent toxicological data on the effects of dilbit and other diluted bitumen products on freshwater organisms and ecosystems are scarce. However, the current literature indicates that dilbit or bitumen can have significant effects on a wide variety of toxicological endpoints. This review synthesizes the currently available literature concerning the fate and effects of dilbit and synbit spilled into freshwater, and the effects of bitumen and bitumen products on aquatic organisms and ecosystems. Dilbit is likely to provide ecological impacts that are similar to and extend from those that follow from exposure to lighter crude oil, but the prospect of bitumen settling after binding to suspended sediments elevates the risk for benthic impacts in streams and lakes. PMID- 26153038 TI - GMDP: unusual physico-chemical and biological properties of the anomeris forms. AB - Disaccharide containing unit of peptidoglycan from bacterial cell wall, N-acetyl d-glucosaminyl-N-acetylmuramyl-l-alanyl-d-glutaminamide (glusosaminyl-muramyl dipeptide) registered in Russia as an immunomodulatory drug, is shown to participate in slow equilibrium of alpha and beta anomeric forms. Data of NMR spectra and molecular dynamics indicate that the alpha-anomer predominantly acquires a folded conformation stabilized by intramolecular hydrogen bond between the alanyl carbonyl and muramyl NH proton. The beta-form displays a considerable fraction of extended, non-hydrogen bonded structures. In the standard immunoadjuvant test system, the alpha-form is practically inactive, and the activity of the equilibrium mixture with alpha : beta = 68 : 32 ratio is due to the presence of beta-anomer. Such unique alpha-beta selectivity of biological action must be considered at the design of related immunoactive glycopeptides. PMID- 26153037 TI - Expression of CD11c and EMR2 on neutrophils: potential diagnostic biomarkers for sepsis and systemic inflammation. AB - There is a need for cellular biomarkers to differentiate patients with sepsis from those with the non-infectious systemic inflammatory response syndrome (SIRS). In this double-blind study we determined whether the expression of known (CD11a/b/c, CD62L) and putative adhesion molecules [CD64, CD97 and epidermal growth factor (EGF)-like molecule containing mucin-like hormone receptor (EMR2)] on blood neutrophils could serve as useful biomarkers of infection and of non infectious SIRS in critically ill patients. We studied 103 patients with SIRS, 83 of whom had sepsis, and 50 healthy normal subjects, using flow cytometry to characterize neutrophils phenotypically in whole blood samples. Patients with SIRS had an increased prevalence of neutrophils expressing CD11c, CD64 and EMR2 in comparison with healthy subjects (P < 0.001), but normal expression of CD11a, CD11b, CD62L and CD97. An increase in the percentage of neutrophils bearing CD11c was associated with sepsis, EMR2 with SIRS and CD64 with sepsis and SIRS. Neutrophils expressing CD11c had the highest sensitivity (81%) and specificity (80%) for the detection of sepsis, and there was an association between the percentage of neutrophils expressing EMR2 and the extent of organ failure (P < 0.05). Contrary to other reports, we did not observe an abnormal expression of CD11b or CD62L on neutrophils from patients with SIRS, and suggest that this discrepancy is due to differences in cell processing protocols. We propose that blood neutrophils expressing CD11c and EMR2 be considered as potential biomarkers for sepsis and SIRS, respectively. PMID- 26153039 TI - Therapeutic Hypothermia for Refractory Status Epilepticus. AB - BACKGROUND: Our goal was to perform a systematic review of the literature on the use of therapeutic hypothermia for refractory status epilepticus (RSE) and its impact on seizure control. METHODS: All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to May 2014), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated by two independent reviewers, using both the Oxford and GRADE methodology. RESULTS: Overall, 13 studies were identified, with 10 manuscripts and 3 meeting abstracts. A total of 40 patients were treated. The common target temperature was 33 degrees Celsius, sustained for a median 48 hours. Patients displayed a 62.5%, 15% and 22.5% rate of seizure cessation, seizure reduction, and failure of treatment respectively. External cooling was utilized in the majority of cases. Deep venous thrombosis, coagulopathy and infections were the commonly reported complications. Two ongoing clinical trials were identified. CONCLUSIONS: Oxford level 4, GRADE D evidence exists to support the use of therapeutic hypothermia to control seizures in RSE. Further prospective study is warranted. PMID- 26153040 TI - Mortality from Parkinson's disease in China: Findings from a five-year follow up study in Shanghai. AB - INTRODUCTION: The mortality of Parkinson's disease (PD) and its associated risk factors among clinically definite PD patients in China has been rarely investigated. Our study aimed to identify the mortality rates and predictors of death in PD patients in China. METHODS: 157 consecutive, clinically definite PD patients from the urban area of Shanghai were recruited from a central hospital based movement disorder clinic in 2006. All patients were regularly followed up at the clinic until December 31, 2011, or death. Mortality and associations with baseline demographics, health and medical factors were then determined within the cohort. RESULTS: After 5 years, 11(7%) patients had died. The standardised mortality ratio was 0.62 (95% CI 0.32 to 1.07, P=0.104). The main causes of death were pneumonia (54.5%, 6/11) and digestive disorders (18.2%, 2/11), respectively. Age at onset, independent living, the mini mental state examination score, the Parkinson's disease sleep scale score and the Epworth sleepiness scale score at baseline were statistically significantly different between the survival group and the deceased group (P<0.05). Across all participants, risk factors for death included low mini mental state examination score, and high Epworth sleepiness scale score according to a binary variable logistic regression analysis. CONCLUSIONS: This study confirms the similar survival of patients with PD to the control population up to a follow-up of 5 years. Interventions tailored to potential risk factors associated with death may offer further benefits. PMID- 26153041 TI - Dilated Virchow-Robin Space and Dopamine Transporter Imaging in the Striatum of Patients with Parkinsonism. AB - OBJECTIVE: The radiological and clinical significance of a dilated Virchow-Robin space (dVRS) in the striatum (STR) remains unclear. We investigated the role of dVRS in STR on parkinsonism and dopamine transporter positron emission tomography (DaT-PET) findings. METHODS: Patients with parkinsonism who underwent both brain magnetic resonance imaging and DaT-PET were included. Clinical status was evaluated by Hoehn and Yahr (HY) stage, Korean-Mini Mental Status Examination (K MMSE), Montreal Cognitive Assessment Korea (MoCA-K), and Frontal Assessment Battery (FAB). dVRS was assessed by semi-quantitative and quantitative scales in each of the three segments of STR (caudate nuclei, anterior and posterior putamen) and was expressed as a dVRS score. DaT-PET was qualitatively assessed as either normal or abnormal in each segment. The relationship between dVRS and DaT PET abnormality (ab-DaT-PET) was designated in each segment as either concordant or discordant. A concordant segment was defined by the presence of dVRS with ab DaT-PET [Concordance rate (CR)=number of concordant segments/number of concordant and discordant segments]. RESULTS: Eleven patients were included. There was no significant correlation between the presence of dVRS and ab-DaT-PET. The mean CR was 0.39. CR was not significantly correlated with any clinical or neuroimaging scales. The dVRS score was significantly correlated with K-MMSE, MoCA-K, and FAB (r=-0.675, -0.847, and -0.868, respectively) but not with HY stage. CONCLUSION: dVRS in STR played no significant role on dopaminergic innervation revealed by DaT-PET and made little contribution to clinical parkinsonism; however, it was correlated with cognitive impairment. PMID- 26153042 TI - A Probable Korean Case of Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay. PMID- 26153043 TI - Pupils in Acute Inflammatory Demyelinating Polyradiculoneuropathy Different From Adies Pupils. PMID- 26153044 TI - Accommodating Presuppositions Is Inappropriate in Implausible Contexts. AB - According to one view of linguistic information (Karttunen, 1974; Stalnaker, 1974), a speaker can convey contextually new information in one of two ways: (a) by asserting the content as new information; or (b) by presupposing the content as given information which would then have to be accommodated. This distinction predicts that it is conversationally more appropriate to assert implausible information rather than presuppose it (e.g., von Fintel, 2008; Heim, 1992; Stalnaker, 2002). A second view rejects the assumption that presuppositions are accommodated; instead, presuppositions are assimilated into asserted content and both are correspondingly open to challenge (e.g., Gazdar, 1979; van der Sandt, 1992). Under this view, we should not expect to find a difference in conversational appropriateness between asserting implausible information and presupposing it. To distinguish between these two views of linguistic information, we performed two self-paced reading experiments with an on-line stops-making-sense judgment. The results of the two experiments-using the presupposition triggers the and too-show that accommodation is inappropriate (makes less sense) relative to non-presuppositional controls when the presupposed information is implausible but not when it is plausible. These results provide support for the first view of linguistic information: the contrast in implausible contexts can only be explained if there is a presupposition-assertion distinction and accommodation is a mechanism dedicated to reasoning about presuppositions. PMID- 26153045 TI - Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen. AB - Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. PMID- 26153046 TI - Effect of IV contrast on lumbar trabecular attenuation at routine abdominal CT: correlation with DXA and implications for opportunistic osteoporosis screening. AB - Osteoporosis remains under-diagnosed. Routine abdominal CT can provide opportunistic screening, but the effect of IV contrast is largely unknown. The overall performance for predicting osteoporosis was similar between enhanced and unenhanced scans. Therefore, both non-contrast and contrast-enhanced abdominal CT scans can be employed for opportunistic osteoporosis screening. INTRODUCTION: Osteoporosis is an important yet under-diagnosed public health concern. Lumbar attenuation measurement at routine abdominal CT can provide a simple opportunistic initial screen, but the effect of IV contrast has not been fully evaluated. METHODS: Mean trabecular CT attenuation values (in Hounsfield units, HU) at the L1 vertebral level were measured by oval region-of-interest (ROI) on both the unenhanced and IV-contrast-enhanced CT series in 157 adults (mean age, 62.0). All patients underwent correlative central DXA within 6 months of CT. Based on DXA BMD of the lumbar spine, femoral neck, and total proximal femur: osteoporosis, osteopenia, and normal BMD was present in 33, 77, and 47, respectively. Statistical analysis included Bland-Altman plots and receiver operating characteristic (ROC) curves. RESULTS: Mean difference (+/-SD) in L1 trabecular attenuation between enhanced and unenhanced CT series was +11.2 HU (+/ 19.2) (95 % CI, 8.16-14.22 HU), an 8 % difference. Intra-patient variation was substantial, but no overall trend in the HU difference was seen according to underlying BMD. ROC area under the curve (AUC) for unenhanced and enhanced CT for diagnosing osteoporosis were similar at 0.818 and 0.830, respectively (p = 0.632). Thresholds for maintaining 90 % specificity for osteoporosis were 90 HU for unenhanced and 102 HU for enhanced CT. Thresholds for maintaining 90 % sensitivity for osteoporosis were 139 HU for unenhanced and 144 HU for enhanced CT. Similar diagnostic performance was seen for diagnosing low BMD (osteoporosis or osteopenia) using higher HU cut-offs. CONCLUSION: Contrast-enhanced CT shows an average increase of 11 HU over the unenhanced series for L1 trabecular attenuation. The overall performance for predicting osteoporosis is similar between the enhanced and unenhanced scans, thus either can be employed for initial opportunistic screening. PMID- 26153047 TI - The role of activated coagulation factor XII in overall clot stability and fibrinolysis. AB - Activated coagulation factor XII (alpha-FXIIa) is able to bind to fibrin(ogen) and increases the density and stiffness of the fibrin clot. Conversely, proteins of the contact system and the fibrinolytic system show a high degree of homology and alpha-FXIIa can convert plasminogen into plasmin resulting in fibrin degradation. Therefore, we studied the contribution of alpha-FXIIa to overall clot stability and plasmin driven fibrinolysis in the absence and presence of tissue plasminogen activator (tPA). We observed that alpha-FXIIa directly converted plasminogen into plasmin and reduced clot lysis time at all tPA concentrations tested (15-1500 pM). Simultaneous assessment of plasmin generation (chromogenic substrate S-2251) and fibrin formation and degradation (absorbance at 405nm), showed an earlier onset of fibrinolysis and plasmin formation in the presence of alpha-FXIIa. Fibrinolysis of clots formed under flow conditions, revealed that incorporation of alpha-FXIIa accelerated clot breakdown (fluorescence release of labeled fibrin) by additional plasmin generation on top of formation by tPA. Scanning electron microscopy (SEM) revealed that the surface area pore size increased in the presence compared with the absence of alpha-FXIIa when fibrinolysis was initiated by the conversion of plasminogen with tPA during clot formation. alpha-FXIIa enhances fibrinolysis in the presence of plasminogen, irrespective of whether tPA was present during clot formation or was added afterwards to initiate fibrinolysis. We postulate that FXIIa first strengthens the clot structure during clot formation and thereafter contributes towards fibrinolysis. PMID- 26153048 TI - Preferential enhancement of laser-driven carbon ion acceleration from optimized nanostructured surfaces. AB - High-intensity ultrashort laser pulses focused on metal targets readily generate hot dense plasmas which accelerate ions efficiently and can pave way to compact table-top accelerators. Laser-driven ion acceleration studies predominantly focus on protons, which experience the maximum acceleration owing to their highest charge-to-mass ratio. The possibility of tailoring such schemes for the preferential acceleration of a particular ion species is very much desired but has hardly been explored. Here, we present an experimental demonstration of how the nanostructuring of a copper target can be optimized for enhanced carbon ion acceleration over protons or Cu-ions. Specifically, a thin (~ 0.25 MUm) layer of 25-30 nm diameter Cu nanoparticles, sputter-deposited on a polished Cu-substrate, enhances the carbon ion energy by about 10-fold at a laser intensity of 1.2 * 10(18) W/cm(2). However, particles smaller than 20 nm have an adverse effect on the ion acceleration. Particle-in-cell simulations provide definite pointers regarding the size of nanoparticles necessary for maximizing the ion acceleration. The inherent contrast of the laser pulse is found to play an important role in the species selective ion acceleration. PMID- 26153049 TI - Bayesian semiparametric analysis of recurrent failure time data using copulas. AB - The analysis of recurrent event data is of particular importance in medical statistics where patients suffering from chronic diseases often present with multiple recurring relapses or cancer patients experience several tumor recurrences. Whereas individual subjects can be assumed to be independent, the times between events of one subject are neither independent nor identically distributed. Apart from the marginal approach by Wei et al. (1989), the shared frailty model, see for example Duchateau and Janssen (2008), has been used extensively to analyze recurrent event data, where the correlation between sequential times is implicitly taken into account via a random effect. Oakes (1989) and Romeo et al. (2006) showed and exemplified the equivalence of frailty models for bivariate survival data to Archimedean copulas. Despite the fact that copula-based models have been used to model parallel survival data, their application to recurrent failure time data has only recently been suggested by Lawless and Yilmaz (2011) for the bivariate case. Here, we extend this to more than two recurrent events and model the joint distribution of recurrent events explicitly using parametric copulas within a Bayesian framework. This framework allows for parametric as well as a nonparametric modeling of the marginal baseline hazards and models the influence of covariates on the marginals via a proportional hazards assumption. Furthermore, the parameters of the copula may also depend on the covariates. We illustrate the flexibility of this approach using data from an asthma prevention trial in young children. PMID- 26153050 TI - [Cases of Fournier's Gangrene in Kinki University]. AB - The aim of our study was to identify risk factors that may influence outcomes for patients presenting with Fournier gangrene. Twelve patients hospitalized and treated between August 2007 and August 2013 were included in this study. Distinct features were noted after one or two weeks of hospitalization. We did not observe a significant correlation between death risk and the extent of necrosis in this patient set. However, the extent of necrosis tended to correlate with the duration of hospitalization in the survivors. We also compared the results of blood biochemical analyses between the surviving and non-surviving groups. A significant difference was noted in the levels of glucose (Glu) after two weeks. In the non-surviving group, Glu levels were increased. These findings suggest a relationship between glycemic control after the initiation of therapy and death. We also examined the results of blood biochemical analyses according to the duration of hospitalization. The lactate dehydrogenase (LDH) levels at admission and LDH levels after two weeks were significantly higher in the patients with a duration of hospitalization longer than the median duration of 61.5 days. These findings suggest a relationship between the duration of hospitalization and the extent of necrosis at diagnosis. PMID- 26153051 TI - [Clinical Review of Hypospermatogenesis in Patients with a Previous Episode of Mumps Orchitis]. AB - This study included 10 patients who had developed mumps orchitis previously and had visited our hospital from January 1997 to November 2007. The present illness, testicular volume and semen analysis of 7 of these patients were retrospectively investigated. Semen analyses and pregnancy statuses were followed up over time. The mean age of the 7 patients was 33 years (range, 21-43 years). Four patients had unilateral (right side) orchitis, and three had bilateral orchitis. In the unilateral orchitis group, 1 patient had an atrophic testis. Findings of semen analysis were severe oligozoospermia in three and mild oligozoospermia in one. None of the patients in the bilateral orchitis group, had atrophic testes. Findings of semen analysis were azoospermia in one and severe oligozoospermia in two patients. Findings of semen analysis in most patients improved gradually, and wives of 2 patients eventually achieved pregnancy. Dysfunction of seminiferous tubules in the diseased testis is thought to be reversible when treated adequately in the initial phase. In the patients not conceiving successfully, testicular sperm extraction (TESE) and assisted reproductive technique (ART) are thought to be effective ways to achieve pregnancy. PMID- 26153052 TI - [Association between Proposed Cancer Foci from the Results of Systematic 12-Core Transrectal Needle Biopsies and Actual Cancer Foci from Radical Prostatectomy Specimens]. AB - We investigated the diagnostic yield for systematic 12-core transrectal prostate needle biopsies. Subjects were 56 prostatic cancer patients who were diagnosed with transrectal ultrasound-guided 12 core prostate needle biopsies and who underwent open retropubic radical prostatectomy. Pathological findings were compared between needle biopsy specimens and total prostatectomy specimens in terms of the presence or absence of cancer foci. For the comparison, the prostate was divided into 5 regions : the apical, middle, basal, far lateral and transitional regions. Then, based on the pathological findings of the biopsies, the sensitivity, specificity, positive predictive value and negative predictive value were calculated for each region. As a result, the sensitivity and the specificity in the transitional region tended to be lower than in other regions, and six of ten false positive lesions were located in the transitional region on the biopsy specimens. Also, the negative predictive value tended to be lower in the apical and far lateral regions. In conclusion, thorough punctures in the apical, transitional, and far lateral regions of the prostate at the systematic transrectal biopsy were paramount important for improving the detection of cancer foci in these regions. PMID- 26153053 TI - [Clear Cell Variant of Invasive Urothelial Carcinoma of the Ureter : A Case Report]. AB - Clear cell variant of invasive urothelial carcinoma is an extremely rare tumor. Here, we report a case of clear cell variant of invasive urothelial carcinoma of the ureter. A 59-year-old man, who complained of gross hematuria was referred to our hospital for precise examination and treatment. Computerized tomographic scanning confirmed the presence of a tumor in the right lower ureter. Urine cytology was positive. He had undergone retroperitoneoscopy-assisted right radical nephroureterectomy. Typical urothelial carcinoma with partial clear cell appearance made it difficult to make a precise pathological diagnosis and immunohistochemical stain helped to diagnosis the case as clear cell variant of invasive urothelial carcinoma. To our knowledge this is the first case of clear cell variant of invasive urothelial carcinoma of the ureter in the world. PMID- 26153054 TI - [Stromal Tumors of Uncertain Malignant Potential (STUMP) of the Prostate : A Case Report]. AB - A 77-year-old man was seen at our hospital with the chief complaint of pollakisuria. Magnetic resonance imaging (MRI) showed a 25 mm cystic tumor with solid components behind the prostate. A transrectal biopsy for the prostate showed no evidence of malignancy. Two years later, he complained of weak urinary stream, and the MRI diagnosis demonstrated an increase of the tumor size to 67 mm. Since prostatic sarcoma was diagnosed by the transrectal biopsy for the prostate, a tumor resection and prostatectomy were performed. At 19 months after the operation, there was no evidence of metastasis or recurrence, and he has had no dysuria. The final pathological diagnosis was of a prostatic STUMP. PMID- 26153055 TI - [A Case of Sarcomatoid Carcinoma of the Penis]. AB - A 75-year-old man visited our hospital complaining of a foul smelling, painful swelling of the glans of the penis. Physical examination showed a true phimosis and a huge solid mass on the glans under the foreskin. After postectomy and penile tumor biopsy, we performed partial penectomy. Histologically, the tumor was composed of atypical spindle cells arranged in an epithelioid pattern and stained positive for both epithelial and mesenchymal markers. Therefore we diagnosed the tumor as sarcomatoid carcinoma of the penis. One month after surgery, advanced gastric cancer was discovered. Thereafter, cancer rapidly spread throughout the whole body, and he died six months postoperatively. PMID- 26153056 TI - Continuous downstream processing for high value biological products: A Review. AB - There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations. PMID- 26153057 TI - Endoscopic ultrasonography-guided drainage of postoperative abdominal fluid collections: What should we do to improve outcomes? PMID- 26153058 TI - Increasing physical activity in patients with mental illness--A randomized controlled trial. AB - OBJECTIVE: The objective of the study was to evaluate whether a motivational volitional intervention program offered in addition to an existing sport program during stationary treatment is capable of establishing a post-stationary increase in physical activity in persons with mental illness. METHODS: N=112 in-patients were initially randomly assigned to the control group (CG; standard rehabilitation) or intervention group (IG; standard rehabilitation plus intervention). Assessments were conducted at four measurement points. RESULTS: At 6 months follow up, the level of exercise in the IG was 95 min/week higher than in the CG (p=.02). The participants of the IG were able to increase their level of goal intention until 6 months follow up (t2: p=.03; t4: p=.005); levels of self-efficacy of the IG increased during intervention (t2: p=.001). Changes in volitional aspects were significant over time (t1-t3), but not specifically for the IG. CONCLUSIONS: The intervention was effective at increasing the level of physical activity in patients with mental illness who were initially minimally active. PRACTICE IMPLICATIONS: Our results suggest that it could be of great use to place the emphasis of a physical activity-enhancing intervention on its motivational effect since volitional aspects are already taken into sufficient account in standard rehabilitation. PMID- 26153059 TI - Association between surgical delay and survival in high-risk emergency abdominal surgery. A population-based Danish cohort study. AB - OBJECTIVE: In patients with perforated peptic ulcer, surgical delay has recently been shown to be a critical determinant of survival. The aim of the present population-based cohort study was to evaluate the association between surgical delay by hour and mortality in high-risk patients undergoing emergency abdominal surgery in general. MATERIAL AND METHODS: All in-patients aged >= 18 years having emergency abdominal laparotomy or laparoscopy performed within 48 h of admission between 1 January 2009 and 31 December 2010 in 13 Danish hospitals were included. Baseline and clinical data, including surgical delay and 90-day mortality were collected. The crude and adjusted association between surgical delay by hour and 90-day mortality was assessed by binary logistic regression. RESULTS: A total of 2803 patients were included. Median age (interquartile range [IQR]) was 66 (51 78) years, and 515 patients (18.4%) died within 90 days of surgery. Over the first 24 h after hospital admission, each hour of surgical delay beyond hospital admission was associated with a median (IQR) decrease in 90-day survival of 2.2% (1.9-3.3%). No statistically significant association between surgical delay by hour and 90-day mortality was shown; crude and adjusted odds ratio with 95% confidence interval 1.016 (1.004-1.027) and 1.003 (0.989-1.017), respectively. Sensitivity analyses confirmed the primary finding. CONCLUSIONS: In the present population-based cohort study of high-risk patients undergoing emergency abdominal surgery, no statistically significant adjusted association between mortality and surgical delay was found. Additional research in diagnosis-specific subgroups of high-risk patients undergoing emergency abdominal surgery is warranted. PMID- 26153060 TI - Cetyltrimethylammonium Bromide-Coated Fe3O4 Magnetic Nanoparticles for Analysis of 15 Trace Polycyclic Aromatic Hydrocarbons in Aquatic Environments by Ultraperformance, Liquid Chromatography With Fluorescence Detection. AB - Accurate determination of polycyclic aromatic hydrocarbons (PAHs) in surface waters is necessary for protection of the environment from adverse effects that can occur at concentrations which require preconcentration to be detected. In this study, an effective solid phase extraction (SPE) method based on cetyltrimethylammonium bromide (CTAB)-coated Fe3O4 magnetic nanoparticles (MNPs) was developed for extraction of trace quantities of PAHs from natural waters. An enrichment factor of 800 was achieved within 5 min by use of 100 mg of Fe3O4 MNPs and 50 mg of CTAB. Compared with conventional liquid-liquid extraction (LLE), C18 SPE cartridge and some newly developed methods, the SPE to determine bioaccessible fraction was more convenient, efficient, time-saving, and cost effective. To evaluate the performance of this novel sorbent, five natural samples including rainwater, river waters, wastewater, and tap water spiked with 15 PAHs were analyzed by use of ultraperformance, liquid chromatography (UPLC) with fluorescence detection (FLD). Limits of determination (LOD) of PAHs (log Kow >= 4.46) ranged from 0.4 to 10.3 ng/L, with mean recoveries of 87.95 +/- 16.16, 85.92 +/- 10.19, 82.89 +/- 5.25, 78.90 +/- 9.90, and 59.23 +/- 3.10% for rainwater, upstream and downstream river water, wastewater, and tap water, respectively. However, the effect of dissolved organic matter (DOM) on recovery of PAHs varied among matrixes. Because of electrostatic adsorption and hydrophobicity, DOM promoted adsorption of Fe3O4 MNPs to PAHs from samples of water from the field. This result was different than the effect of DOM under laboratory conditions. Because of competitive adsorption with the site of action on the surface of Fe3O4 MNPs for CTAB, recoveries of PAHs were inversely proportional to concentrations of Ca(2+) and Mg(2+). This novel sorbent based on nanomaterials was effective at removing PAHs at environmentally relevant concentrations from waters containing relevant concentrations of both naturally occurring organic matter and hardness metals. PMID- 26153061 TI - Developing Xenopus embryos recover by compacting and expelling single wall carbon nanotubes. AB - Single wall carbon nanotubes are high aspect ratio nanomaterials being developed for use in materials, technological and biological applications due to their high mechanical stiffness, optical properties and chemical inertness. Because of their prevalence, it is inevitable that biological systems will be exposed to nanotubes, yet studies of the effects of nanotubes on developing embryos have been inconclusive and are lacking for single wall carbon nanotubes exposed to the widely studied model organism Xenopus laevis (African clawed frog). Microinjection of experimental substances into the Xenopus embryo is a standard technique for toxicology studies and cellular lineage tracing. Here we report the surprising finding that superficial (12.5 +/- 7.5 um below the membrane) microinjection of nanotubes dispersed with Pluronic F127 into one- to two-cell Xenopus embryos resulted in the formation and expulsion of compacted, nanotube filled, punctate masses, at the blastula to mid-gastrula developmental stages, which we call "boluses." Such expulsion of microinjected materials by Xenopus embryos has not been reported before and is dramatically different from the typical distribution of the materials throughout the progeny of the microinjected cells. Previous studies of microinjections of nanomaterials such as nanodiamonds, quantum dots or spherical nanoparticles report that nanomaterials often induce toxicity and remain localized within the embryos. In contrast, our results demonstrate an active recovery pathway for embryos after exposure to Pluronic F127-coated nanotubes, which we speculate is due to a combined effect of the membrane activity of the dispersing agent, Pluronic F127, and the large aspect ratio of nanotubes. PMID- 26153062 TI - High-resolution microarray analysis unravels complex Xq28 aberrations in patients and carriers affected by X-linked blue cone monochromacy. AB - The human X chromosome contains ~ 1600 genes, about 15% of which have been associated with a specific genetic condition, mainly affecting males. Blue cone monochromacy (BCM) is an X-linked condition caused by a loss-of-function of both the OPN1LW and OPN1MW opsin genes. The cone opsin gene cluster is composed of 2-9 paralogs with 99.8% sequence homology and is susceptible to deletions, duplications, and mutations. Current diagnostic tests employ polymerase chain reaction (PCR)-based technologies; however, alterations remain undetermined in 10% of patients. Furthermore, carrier testing in females is limited or unavailable. High-resolution X chromosome-targeted CGH microarray was applied to test for rearrangements in males with BCM and female carriers from three unrelated families. Pathogenic alterations were revealed in all probands, characterized by sequencing of the breakpoint junctions and quantitative real time PCR. In two families, we identified a novel founder mutation that consisted of a complex 3-kb deletion that embraced the cis-regulatory locus control region and insertion of an additional aberrant OPN1MW gene. The application of high resolution X-chromosome microarray in clinical diagnosis brings significant advantages in detection of small aberrations that are beyond the resolution of clinically available aCGH analysis and which can improve molecular diagnosis of the known conditions and unravel previously unrecognized X-linked diseases. PMID- 26153063 TI - Repair of short type IV laryngotracheoesophageal cleft using long, tapered, engaging graft without need for tracheotomy. AB - An infant with a type IV laryngotracheoesophageal cleft underwent transcervical repair using a long tapered cartilage graft. A laryngofissure was carried down to the innominate artery to expose the cleft that extended 5 mm inferior to the vessel. The edges of the cleft were excised, the trachealis was separated from the esophagus that was reapproximated, and clavicular periosteum was placed. A long posterior costal cartilage graft that tapered inferiorly in anteroposterior dimension and engaged behind the cricoid plate was inserted. This added rigidity to the repair and obviated the need for a tracheotomy while providing a four layer closure. LEVEL OF EVIDENCE: NA. PMID- 26153064 TI - Letter regarding the article of Tauzin et al. 'Increased systemic blood pressure and arterial stiffness in young adults born prematurely'. PMID- 26153065 TI - Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing kappa-, MU-opioid and nociceptin receptors. AB - Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via kappa- (KOP), MU-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. Buprenorphine, when applied acutely, inhibited AC activity to ~90% in cells expressing KOP+MOP+NOP receptors. Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. PMID- 26153066 TI - Some of the people, some of the time: field evidence for associations and dissociations between stress and drug use. AB - RATIONALE: Stress's role in drug use is supported by retrospective interview and laboratory studies, but prospective data confirming the association in daily life are sparse. OBJECTIVES: This study aims to assess the relationship between drug use and stress in real time with ambulatory monitoring. METHODS: For up to 16 weeks, 133 outpatients on opiate agonist treatment used smartphones to report each time they used drugs or felt more stressed than usual. They rated stress event severity on a 10-point scale and as a hassle, day spoiler, or more than a day spoiler. For analysis, stress reports made within 72 h before a reported use of cocaine or opioid were binned into 24-h periods. RESULTS: Of 52 participants who reported stress events in the 72-h timeframe, 41 reported stress before cocaine use and 26 before opioid use. For cocaine use, the severity of stressors, rated numerically (r effect = 0.42, CL95 0.17-0.62, p = 0.00061) and percent rated as "more than a day spoiler" (r effect = 0.34, CL95 0.07-0.56, p = 0.0292)], increased linearly across the three days preceding use. The number of stressors did not predict cocaine use, and no measure of stress predicted opioid use. In ecological momentary assessment (EMA) from the whole sample of 133, stress and drug use occurred independently and there was no overall relationship. CONCLUSIONS: EMA did not support the idea that stress is a necessary or sufficient trigger for cocaine or heroin use after accounting for the base rates of stress and use. But EMA did show that stressful events can increase in severity in the days preceding cocaine use. PMID- 26153067 TI - A subanesthetic dose of ketamine in the Rhesus monkey reduces the occurrence of anticipatory saccades. AB - RATIONALE: It has been shown that antagonism of the glutamatergic N-methyl-D aspartate (NMDA) receptor with subanesthetic doses of ketamine perturbs the perception of elapsed time. Anticipatory eye movements are based on an internal representation of elapsed time. Therefore, the occurrence of anticipatory saccades could be a particularly sensitive indicator of abnormal time perception due to NMDA receptors blockade. OBJECTIVES: The objective of this study was to determine whether the occurrence of anticipatory saccades could be selectively altered by a subanesthetic dose of ketamine. METHODS: Three Rhesus monkeys were trained in a simple visually guided saccadic task with a variable delay. Monkeys were rewarded for making a visually guided saccade at the end of the delay. Premature anticipatory saccades to the future position of the eccentric target initiated before the end of the delay were not rewarded. A subanesthetic dose of ketamine (0.25 mg/kg) or a saline solution of the same volume was injected i.m. during the task. RESULTS: We found that the injected dose of ketamine did not induce sedation or abnormal behavior. However, in ~4 min, ketamine induced a strong reduction of the occurrence of anticipatory saccades but did not reduce the occurrence of visually guided saccades. CONCLUSION: This unexpected reduction of anticipatory saccade occurrence could be interpreted as resulting from an altered use of the perception of elapsed time during the delay period induced by NMDA receptors antagonism. PMID- 26153069 TI - Outcomes for multilevel surgery for sleep apnea: Obstructive sleep apnea, transoral robotic surgery, and uvulopalatopharyngoplasty. AB - OBJECTIVES/HYPOTHESIS: This study evaluates the outcomes of multilevel surgery for patients with obstructive sleep apnea (OSA) who underwent transoral robotic surgery (TORS) (i.e., posterior glossectomy and limited lateral pharyngectomy) with uvulopalatopharyngoplasty (UPPP). STUDY DESIGN: Prospective, nonrandomized trial with historical controls. METHODS: All patients underwent pre- and postoperative polysomnography, preoperative magnetic resonance imaging of the neck, preoperative drug-induced sleep endoscopy, surgery, including UPPP if this had not occurred previously, and OSA TORS. Outcomes measures included apnea hypopnea index (AHI), Epworth Sleepiness Scale (ESS), O2 saturation nadir, and total sleep time spent at < 90% O2 saturation. RESULTS: Patients who had no prior surgery achieved an average AHI reduction from 58.4 to 19.5 (67%, P < .0001), a surgical success rate of 56%, and a surgical response rate of 73%. Patients with prior pharyngeal surgery achieved an AHI reduction from 55.0 to 45 (24%, P = .19), a surgical success rate of 30%, and a surgical response rate of 40%. Total sleep time spent at <90% O2 saturation was improved from 14% to 3.6% (P < .0003) for patients without prior surgery, and 21.1% to 12.5% (P < .17)for those with prior surgery. ESS improved for all patients combined from 12.8 to 5.8 (P < .0001). CONCLUSIONS: Outcomes for the combined approach of OSA TORS and UPPP provide strong evidence in favor of this multilevel approach for the surgical management of OSA. The benefit of the current surgical approach is most significant for previously unoperated patients. PMID- 26153068 TI - Acetaldehyde sequestration by D-penicillamine prevents ethanol relapse-like drinking in rats: evidence from an operant self-administration paradigm. AB - RATIONALE: Previous experiments in our laboratory have shown that D-penicillamine (DP) (acetaldehyde sequestering agent) is able to block the increase in ethanol consumption observed after a period of imposed deprivation (the so-called alcohol deprivation effect (ADE)), using a non-operant paradigm in Wistar rats. OBJECTIVES: This study is aimed at investigating the robustness and reproducibility of our previous data using an operant paradigm, which is considered to be a valid and reliable model of human drug consumption, and the ADE, probably the most often used measure of ethanol relapse-drinking behaviour in rats. METHODS: Male Wistar rats with a limited (30-min sessions), intermittent and extended background of ethanol operant self-administration were used. In order to evaluate the efficacy of several DP doses (6.25, 12.5 and 25 mg/kg i.p.) in preventing alcohol relapse, we set up a protocol based on the ADE. In a separate experiment, the effect of DP on spontaneous motor activity of rats was also tested. RESULTS: A significant ADE was observed in animals treated with saline. DP treatment blocked the increase in ethanol responses following the imposed abstinence period. The higher dose suppressed the ADE and provoked a significant reduction in ethanol consumption with respect to the baseline conditions. Basal motor activity was not altered after DP treatment. CONCLUSION: Our positive results with DP, using two different paradigms that evaluate relapse of ethanol drinking, will help to increase the positive predictive value of pre clinical experiments and offer a solid base to inspire human studies with DP. PMID- 26153070 TI - Quercetin improves the activity of the ubiquitin-proteasomal system in 150Q mutated huntingtin-expressing cells but exerts detrimental effects on neuronal survivability. AB - Quercetin, a strong free radical scavenger, is investigated for neuroprotective effects in a Neuro 2a cell line conditionally transfected with 16Q huntingtin (Htt) and 150Q Htt, which express the protein upon stimulation. Cells were protected from death by a 20-uM dose of quercetin on the second day of Htt induction, but 30-100-uM doses of the drug caused further toxicity in both 16Q and 150Q cells, as indicated by MTT assay and by significant reductions in the number of cells bearing neurites on the second day. A significant decrease in the number of cells containing aggregate was seen in induced 150Q cells treated with 20 uM but not for those treated with 40 or 50 uM quercetin up to 4 days of induction. Mutated Htt (mHtt)-induced reduction in proteasomal activity of the ubiquitin-proteasomal system (UPS) was significantly attenuated by 20 uM quercetin. However, neither mitochondrial membrane potential loss nor colocalization of 20S proteasome with mHtt aggregate was corrected by quercetin treatment. Our results imply that the neuroprotective effect of quercetin arises out of the upregulation of UPS activity, which causes a decrease in the number of mHtt aggregate-harboring cells. The increased neurotoxicity could result from the continued association of mHtt with 20S proteasome and the failure of quercetin to correct mitochondrial membrane potential loss. These results suggest that, although quercetin at a low dose protects against mHtt-mediated cell death, higher doses are toxic to the cells, clearly demarcating a narrow therapeutic window for this dietary flavonoid. PMID- 26153071 TI - Initial Stability of Subtrochanteric Oblique Osteotomy in Uncemented Total Hip Arthroplasty: A Preliminary Finite Element Study. AB - BACKGROUND: Subtrochanteric oblique osteotomy (SOO) has been widely used to reconstruct highly dislocated hips in uncemented total hip arthroplasty. The occurrence of complications can be attributed to the instability of the osteotomy region. The aim of this study was to evaluate the initial stability of SOO in uncemented total hip arthroplasty. MATERIAL AND METHODS: A 3-dimensional finite element femur-stem model was created, and a virtual SOO was performed at 4 oblique angles: 30 degrees , 45 degrees , 60 degrees , and 90 degrees . The von Mises stress distribution in the femur-stem complex and the displacement under different oblique angles were evaluated in the SOO models, in comparison with that of the intact model. RESULTS: The study demonstrated that the distal fragment of the femur bore more stresses than the proximal fragment, and the maximum stress was concentrated in the femoral neck and the cortical bone, which contacted with the distal end of the stem. SOO increased the stress of both the femur and the stem, and fractures may occur in the stress concentration sites. Additionally, comparing the displacement at different oblique angles, the lateral region was larger than that of the medial region on the subtrochanteric osteotomy plane. The minimum micromotion on the osteotomy plane was obtained when the oblique angle was 45 degrees . CONCLUSIONS: The fit and fill of the distal fragment of the femur and the stem is essential for the stability of the subtrochanteric osteotomy region. The optimal oblique angle for SOO appears to be 45 degrees . PMID- 26153072 TI - Reconsideration of the clinical and histopathological significance of angiogenesis in prostate cancer: Usefulness and limitations of microvessel density measurement. AB - Angiogenesis plays important roles in tumor growth and cancer cell dissemination in almost all cancers. In prostate cancer, there is general agreement that increased angiogenesis is an important factor in determining tumor development and prognosis in these patients. Microvessel density is recognized as a useful marker for evaluating the angiogenic status of cancer tissues. Many investigators have reported that microvessel density is significantly associated with pathological features and outcomes in prostate cancer patients; however, some researchers have expressed opposing opinions. As the reason for such discrepancy, previous reports have suggested differences in the methodologies of measuring microvessel density in cancer tissues. In the present review, we focus on the variation in such methods, including the selected area and the method used for (semi)quantification. In particular, we discuss the relationship between malignancy potential, tumor progression, and survival and differences in the antibodies used for detection of endothelial cells in detail. We briefly compare the pathological significance and prognostic roles of microvessel density measured using von Willebrand factor, CD31, CD34, and CD105. Based on these analyses, the advantages and limitations of microvessel density measurements in prostate cancer tissues are clarified. Improved "real" and "specific" markers of cancer-related angiogenesis are necessary for better predictions of prognoses and for discussion of treatment strategies for patients with prostate cancer. However, establishment of a satisfactory cancer-related endothelial marker could take a long time. Therefore, knowledge regarding the pathological significance of microvessel density - based on understanding of the advantages and limitations of microvessel density determination methods - is important. PMID- 26153073 TI - Comparison of Homeless and Non-Homeless Problem Drug Users Recruited from Primary Care Safety-Net Clinics. AB - INTRODUCTION: The present study of homeless non-treatment-seeking problem drug users was designed to complement and extend previous studies which focused exclusively on treatment-seeking homeless problem drug users. METHOD: Data were available for 866 primary care patients with drug problems, 30% homeless and 70% housed. RESULTS: In the 2 years prior to baseline, homeless participants had less chronic medical co-morbidity than problem drug users who were housed yet were significantly more likely to have used emergency department services, to have used them more frequently, and at higher cost. Compared to their housed counterparts, homeless participants were also more likely to have been admitted to specialized chemical dependency treatment and/or detoxification services, to have been arrested for a felony or gross misdemeanor, and to report having psychiatric problems in the prior 30 days. CONCLUSIONS: Additional support may be necessary for homeless patients presenting in primary care to benefit from substance abuse treatment given their more severe drug use problems coupled with their co-morbid health, psychiatric, and psychosocial problems. PMID- 26153074 TI - Chemical profiling and anti-psoriatic activity of methanolic extract of Andrographis nallamalayana J.L.Ellis. AB - Andrographis nallamalayana is being widely used as tribal medicine in the treatment of leucoderma and mouth ulcers. Chemical profiling of methanolic extract of the whole plant (PE), using GC-MS and LC-MS, revealed the presence of compounds viz. alpha-tocopherol, beta-sitosterol, tetradecanoic acid, monostearin, flavones/flavanones and their glycosides, chromones, etc. Topical application of imiquimod on the dorsal portion of male BALB/C mice resulted in the development of psoriatic symptoms (erythema, scaling, thickening and folding) with a mean disease activity index (DAI) of >7.0. Topical treatment with 100-MUL PE (~6.4%/12.8%) formulations, for 12-days, resulted in the alleviation of disease symptoms. Compared to water-based formulations, emu oil-based formulation, PE400EO was found more effective in reducing the mean DAI (>84%), keratinocyte count (>65%) (p < 0.01) and interleukin-22 (~70%) (p < 0.05). We report, for the first time, anti-psoriatic activity of A. nallamalayana having great potential in developing a potent phytomedicine against psoriasis. PMID- 26153076 TI - SWEEP: A Tool for Filtering High-Quality SNPs in Polyploid Crops. AB - High-throughput next-generation sequence-based genotyping and single nucleotide polymorphism (SNP) detection opens the door for emerging genomics-based breeding strategies such as genome-wide association analysis and genomic selection. In polyploids, SNP detection is confounded by a highly similar homeologous sequence where a polymorphism between subgenomes must be differentiated from a SNP. We have developed and implemented a novel tool called SWEEP: Sliding Window Extraction of Explicit Polymorphisms. SWEEP uses subgenome polymorphism haplotypes as contrast to identify true SNPs between genotypes. The tool is a single command script that calls a series of modules based on user-defined options and takes sorted/indexed bam files or vcf files as input. Filtering options are highly flexible and include filtering based on sequence depth, alternate allele ratio, and SNP quality on top of the SWEEP filtering procedure. Using real and simulated data we show that SWEEP outperforms current SNP filtering methods for polyploids. SWEEP can be used for high-quality SNP discovery in polyploid crops. PMID- 26153075 TI - GFP Loss-of-Function Mutations in Arabidopsis thaliana. AB - Green fluorescent protein (GFP) and related fluorescent proteins are widely used in biological research to monitor gene expression and protein localization in living cells. The GFP chromophore is generated spontaneously in the presence of oxygen by a multi-step reaction involving cyclization of the internal tripeptide Ser65 (or Thr65)-Tyr66-Gly67, which is embedded in the center of an 11-stranded beta-barrel structure. Random and site-specific mutagenesis has been used to optimize GFP fluorescence and create derivatives with novel properties. However, loss-of-function mutations that would aid in understanding GFP protein folding and chromophore formation have not been fully cataloged. Here we report a collection of ethyl methansulfonate-induced GFP loss-of-function mutations in the model plant Arabidopsis thaliana. Mutations that alter residues important for chromophore maturation, such as Arg96 and Ser205, greatly reduce or extinguish fluorescence without dramatically altering GFP protein accumulation. By contrast, other loss-of-fluorescence mutations substantially diminish the amount of GFP protein, suggesting that they compromise protein stability. Many mutations in this category generate substitutions of highly conserved glycine residues, including the following: Gly67 in the chromogenic tripeptide; Gly31, Gly33, and Gly35 in the second beta-strand; and Gly20, Gly91, and Gly127 in the lids of the beta-barrel scaffold. Our genetic analysis supports conclusions from structural and biochemical studies and demonstrates a critical role for multiple, highly conserved glycine residues in GFP protein stability. PMID- 26153077 TI - Targeted Modification of Gene Function Exploiting Homology-Directed Repair of TALEN-Mediated Double-Strand Breaks in Barley. AB - Transcription activator-like effector nucleases open up new opportunities for targeted mutagenesis in eukaryotic genomes. Similar to zinc-finger nucleases, sequence-specific DNA-binding domains can be fused with effector domains like the nucleolytically active part of FokI to induce double-strand breaks and thereby modify the host genome on a predefined target site via nonhomologous end joining. More sophisticated applications of programmable endonucleases involve the use of a DNA repair template facilitating homology-directed repair (HDR) so as to create predefined rather than random DNA sequence modifications. The aim of this study was to demonstrate the feasibility of editing the barley genome by precisely modifying a defined target DNA sequence resulting in a predicted alteration of gene function. We used gfp-specific transcription activator-like effector nucleases along with a repair template that, via HDR, facilitates conversion of gfp into yfp, which is associated with a single amino acid exchange in the gene product. As a result of co-bombardment of leaf epidermis, we detected yellow fluorescent protein accumulation in about three of 100 mutated cells. The creation of a functional yfp gene via HDR was unambiguously confirmed by sequencing of the respective genomic site. In addition to the allele conversion accomplished in planta, a readily screenable marker system is introduced that might be useful for optimization approaches in the field of genome editing. PMID- 26153078 TI - Pacemaker role of pericytes in generating synchronized spontaneous Ca2+ transients in the myenteric microvasculature of the guinea-pig gastric antrum. AB - Properties of spontaneous Ca(2+) transients in the myenteric microvasculature of the guinea-pig stomach were investigated. Specifically, we explored the spatio temporal origin of Ca(2+) transients and the role of voltage-dependent Ca(2+) channels (VDCCs) in their intercellular synchrony using fluorescence Ca(2+) imaging and immunohistochemistry. The microvasculature generated spontaneous Ca(2+) transients that were independent of both Ca(2+) transients in interstitial cells of Cajal (ICC) and neural activity. Spontaneous Ca(2+) transients were highly synchronous along the length of microvasculature, and appeared to be initiated in pericytes and spread to arteriolar smooth muscle cells (SMCs). In most cases, the generation or synchrony of Ca(2+) transients was not affected by blockers of L-type VDCCs. In nifedipine-treated preparations, synchronous spontaneous Ca(2+) transients were readily blocked by Ni(2+), mibefradil or ML216, blockers for T-type VDCCs. These blockers also suppressed the known T-type VDCC dependent component of ICC Ca(2+) transients or slow waves. Spontaneous Ca(2+) transients were also suppressed by caffeine, tetracaine or cyclopiazonic acid (CPA). After the blockade of both L- and T-type VDCCs, asynchronous Ca(2+) transients were generated in pericytes on precapillary arterioles and/or capillaries but not in arteriolar SMCs, and were abolished by CPA or nominally Ca(2+) free solution. Together these data indicate that pericytes in the myenteric microvasculature may act as the origin of synchronous spontaneous Ca(2+) transients. Pericyte Ca(2+) transients arise from Ca(2+) release from the sarco-endoplasmic reticulum and the opening of T-type Ca(2+) VDCCs is required for their synchrony and propagation to arteriolar SMCs. PMID- 26153079 TI - Fragile-X syndrome--a 20-year follow-up study of male patients. AB - In 1994, a multi-professional team examined clinically 34 males with fragile X syndrome (FXS). Since then, these patients have been clinically evaluated twice at a 10-year interval. With the aid of the Portage method we were able to chart the course of their adaptive skills. The FXS males learned new abilities on average up to the age of 25; this was followed by a plateau stage until they reached 50, after which time, physical symptoms evidencing weakened overall motor skills were apparent. During follow-up, a total of 10 men died, 9 of them suddenly. Of these, three were under the age of 40 at death, and the oldest was 77. The FXS men were socially interactive, helpful, but shy. Typical symptoms of FXS boys such as poor eye contact, tactile defensiveness, and perseverative speech did not disappear with age. At the end of the study, 75% of the study subjects had long-standing health problems. Most aged over 50 suffered from symptoms arising from an enlarged prostate; one fourth were on psychotropic-, and one fifth on antiepileptic drug treatment. PMID- 26153080 TI - Hantavirus infection among children hospitalized for febrile illness suspected to be dengue in Barbados. AB - Emerging picture of hantavirus infection in the South America is characterized by greater proportion of childhood infection and wider spectrum of disease from mild asymptomatic to lethal cardiopulmonary disease. Barbados is endemic for dengue and leptospirosis, both of which share clinical features with hantavirus infection and in many cases neither of these diagnosis could be confirmed. We investigate whether some of the children hospitalized with suspected dengue could indeed have been hantavirus infections. In this prospective study children hospitalized with suspected dengue were tested for hantavirus infection using ELISA for the IgM antibodies. Thirty-eight children tested positive for hantavirus infection. They presented with fever, headache and mild respiratory and gastrointestinal symptoms and signs. None of them had features suggestive of hantavirus cardiopulmonary syndrome. Blood count values ranged from low to normal to high for their age. There were no deaths. Hantavirus infection is prevalent in this Caribbean country. It predominantly presents with milder disease and is responsible for some of the nonspecific febrile illnesses in children. PMID- 26153081 TI - Stochastic effects in adaptive reconstruction of body damage: implied the creativity of natural selection. AB - After an injury occurs, mechanical/biochemical loads on muscles influence the composition and structure of recovering muscles; this effect likely occurs in other tissues, cells and biological molecules as well owing to the similarity, interassociation and interaction among biochemical reactions and molecules. The 'damage and reconstruction' model provides an explanation for how an ideal cytoarchitecture is created by reducing components not suitable for bearing loads; in this model, adaptive changes are induced by promoting the stochasticity of biochemical reactions. Biochemical and mechanical loads can direct the stochasticity of biochemical reactions, which can in turn induce cellular changes. Thus, mechanical and biochemical loads, under natural selection pressure, modify the direction of cell- and tissue-level changes and guide the formation of new structures and traits, thereby influencing microevolution. In summary, the 'damage and reconstruction' model accounts for the role of natural selection in the formation of new organisms, helps explain punctuated equilibrium, and illustrates how macroevolution arises from microevolution. PMID- 26153082 TI - Colon carcinogenesis in wild type and immune compromised mice after treatment with azoxymethane, and azoxymethane with dextran sodium sulfate. AB - The association between inflammation and the risk of colorectal cancer (CRC) is well documented in animal models and in humans, but the mechanistic role of inflammation in CRC is less well understood. To address this question, the induction of colon tumors was evaluated in (i) wild type (WT) and athymic BALB/c mice treated with the colon carcinogen azoxymethane (AOM) as a single agent, and (ii) in an inflammation model of colon cancer employing AOM and dextran sodium sulfate (DSS) in WT, athymic, TCRbeta(-/-) , TCRdelta(-/-) and TCRbeta(-/-) TCRdelta(-/-) C57Bl/6 mice. The athymic BALB/c mice treated with only AOM developed 90% fewer tumors than the WT mice. The difference in response was not due to metabolic activation of AOM or repair of DNA adducts. In the inflammation model using a standard sequential exposure to AOM followed by DSS treatment, the tumor incidence in WT mice was 58% with 7 adenomas and 6 adenocarcinomas. In contrast, the TCRbeta(-/-) , TCRdelta(-/-) and TCRbeta(-/-) TCRdelta(-/-) C57Bl/6 mice showed adenoma incidences of 10, 33, and 11%, respectively, and none of the immune compromised mice developed adenocarcinomas. When the DSS exposure was increased and the AOM lowered, no difference was observed between WT and TCRbeta( /-) mice due to an increase in the incidence in the TCR null mice without concomitant increase in the WT mice. No tumors were observed in mice treated with AOM or DSS alone. (c) 2015 Wiley Periodicals, Inc. PMID- 26153083 TI - It is time to review how unlicensed medicines are used. AB - The safe and effective use of medicines is an integral part of the medicine safety agenda. We present a phenomenological topic review of the literature relating to the use of unlicensed medicines (ULM). There is evidence to demonstrate that the use of ULM is associated with increased incidence of adverse drug reactions, and that despite advances in medicine regulation and guidance from professional organisations, the use of ULM in at risk populations has not reduced. There is also evidence to suggest that patients and their carers are not being provided with adequate information about their medicines and that ULM are being used where safer licensed alternatives are available. This is contrary to the philosophy of "patient-focussed care". We conclude that organisational governance processes and professional guidelines have not kept pace with regulatory developments or changes in legal and ethical understanding. We recommend that governance procedures for ULM be updated across healthcare settings to ensure that patients are involved in the decisions made about their medicines including the regulatory status of the medicine. This includes ensuring adequate consent is obtained from the patient (or their advocate). We also recommend that professional bodies clarify their position on when ULM can be used instead of licensed medicines to ensure that licensed medicines are used wherever possible. In the current economic environment, commissioners and clinicians must resist the temptation to use lower-quality ULM in place of licensed ones to cut costs. We go on to recommend areas of further research including the extent of ULM prescribing where licensed alternatives exist and the geographical and social factors that influence clinician prescribing of ULM. PMID- 26153085 TI - Transient receptor potential channel superfamily: Role in lower urinary tract function. AB - Lower urinary tract symptoms associated with neurogenic bladder and overactive bladder syndrome are mediated in part by members of the transient receptor potential channel superfamily. The best studied member of this superfamily is the vanilloid receptor. Other transient receptor potential channels, such as the melastatin receptor and the ankyrin receptor, are also active in the pathogenesis of lower urinary tract dysfunction. However, the detailed mechanisms by which the transient receptor potential channels contribute to lower urinary tract symptoms are still not clear, and the therapeutic benefits of modulating transient receptor potential channel activity have not been proved in the clinical setting. In the present review, to better understand the pathophysiology and therapeutic potential for lower urinary tract symptoms, we summarize the presence and role of different members of the transient receptor potential channel superfamily in the lower urinary tract. PMID- 26153084 TI - CYP2B6 rs2279343 polymorphism is associated with smoking cessation success in bupropion therapy. AB - BACKGROUND: Previous studies suggested that polymorphisms in the CYP2B6 gene (which encodes an isoenzyme that metabolizes bupropion) and in the ANKK1 gene (which is located in the ANKK1/DRD2 gene cluster) might influence response to therapy. Thus, the aim of the present study was to evaluate whether the CYP2B6 and ANKK1 polymorphisms are associated with the response to smoking cessation therapies in patients from a smoking cessation assistance program. METHODS: The cohort study enrolled 478 smokers who received behavioral counseling and drug therapy (bupropion, nicotine replacement therapy, and/or varenicline). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerstrom test for nicotine dependence (FTND) and Issa situational smoking scores were analyzed for nicotine dependence (ND). The ANKK1 rs1800497, CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371), and CYP2B6*9 (rs3745274) polymorphisms were genotyped by high resolution melting analysis or by restriction fragment length polymorphism. RESULTS: Patients with CYP2B6 rs2279343 wild-type AA genotype had higher success rate (48.0 %) compared with patients carrying AG or GG genotypes (CYP2B6*4 variant) (35.5 %) on bupropion therapy. The AA genotype was associated with higher OR for success during bupropion therapy (OR = 1.92, 95 % CI = 1.08-3.42, p = 0.03) in a multivariate model. We did not observe significant differences in the FTND and Issa scores according to the studied polymorphisms. CONCLUSION: We showed that patients with CYP2B6*4 (rs2279343) variant had lower success rate with bupropion. Likely, the CYP2B6*4 variant, which leads to a rapid predicted metabolic phenotype for the isoenzyme, influences the pharmacological activity of bupropion. Our finding suggests that CYP2B6*4 may be an important genetic marker for individualized bupropion pharmacotherapy. PMID- 26153086 TI - Antioxidant activity of honey supplemented with bee products. AB - The aim of this work was to evaluate the influence of supplementation of multiflower honey with bee products on the phenolic compound content and on antioxidant activity. Average total phenolic and flavonoids contents in the multiflower honeys were 36.06 +/- 10.18 mg GAE/100 g and 4.48 +/- 1.69 mg QE/100 g, respectively. The addition of royal jelly did not affect significantly the phenolic compound content and antioxidant activity. Supplementation of honey with other bee products, i.e. beebread, propolis, pollen, resulted in significant increase in the total phenolic and flavonoids contents, and in antiradical activity and reducing power, with the largest effect found for addition of beebread. Significant linear correlations between the total phenolic and flavonoids contents and antiradical activity and reducing power were found. PMID- 26153087 TI - The effect of cochlear implantation on tinnitus in patients with bilateral hearing loss: A systematic review. AB - OBJECTIVES: To present an overview of the effect of cochlear implantation on tinnitus in adults with bilateral sensorineural hearing loss. DATA SOURCES: PubMed, Cochrane Library, CINAHL, and Embase databases were searched for articles from database inception up to January 13, 2015. METHODS: A systematic search was conducted. Original studies reporting on cochlear implantation and the effect on tinnitus, measured with a tinnitus questionnaire, were included. The directness of evidence and risk of bias were assessed. Studies with a moderate or high directness of evidence and a low or moderate risk of bias were included for analysis. The pre- and postimplantation tinnitus scores were extracted. RESULTS: In total, 786 unique articles were retrieved. Although there was lack of high level of evidence studies, 10 articles satisfied the eligibility criteria. Overall, there was a reduction of mean tinnitus score. There was a decrease in tinnitus score in 25% to 72%, and a total suppression of tinnitus after implantation was reported in 8% to 45% of patients. Tinnitus was stable in 0% to 36% of patients, and increase of tinnitus occurred in 0% to 25%. Tinnitus induction rates in the patients without preoperative tinnitus varied from 0% to 10%. CONCLUSIONS: There are no high level of evidence studies concerning cochlear implantation and the effect on tinnitus. Overall, current literature shows that there is a decrease of mean tinnitus questionnaire score after unilateral cochlear implantation. However, there is also a chance of increasing burden of existing tinnitus, and the induction of tinnitus is reported. LEVEL OF EVIDENCE: NA. PMID- 26153089 TI - End-of-life management in children. PMID- 26153088 TI - [Drugs cardiotoxicity]. AB - Thanks to science advances, cancer is no longer synonymous with death. Life expectancy improvement reveals a new problem: cancer treatment toxicity, including cardiovascular complications, responsible for significant morbidity and mortality. Media scandal of drug-induced valvular heart disease did revise the risk-benefit balance of drugs used (often off-label) as anorectics. Today's society uses drugs heavily but does not accept their side effects. Knowledge and information of these complications is essential. Coronary toxicity of some treatments or drugs commonly used must be known. PMID- 26153090 TI - Trends in mortality after cancer diagnosis: A nationwide cohort study over 45 years of follow-up in Sweden by country of birth. AB - BACKGROUND: Survival has steadily improved for major cancer types in most parts of the world. We compared all-cause mortality between foreign-born and Sweden born residents of Sweden who were diagnosed with cancer of the colon, lung, stomach, prostate, breast, cervix, and all site. METHODS: We used Swedish national vital status and health registers to follow a cohort of 1,556,108 patients 45 years of age and older diagnosed with cancer between 1961 and 2009 in Sweden. Among them, 109,915 were born abroad. We estimated hazard ratios (HR) and 95% confidence interval (CI) using multivariable Cox proportional hazard models. RESULTS: We identified 604,035 and 540,138 deaths among men and women, respectively. Among them 33,595 men and 34,174 women were born abroad. At the time of diagnosis, patients born abroad were on average 4 years younger than patients born in Sweden. All-cause mortality was generally lower in the former than in the latter group of patients before 1990 but higher after 2000. The mortality trend was similar for prostate and breast cancer. CONCLUSIONS: Whilst national policy in Sweden aims at achieving equal access to health care, the mortality trend observed among cancer patients born in Sweden was different from that observed among patients born elsewhere. Mortality after diagnosis of major types of cancer has worsened among foreign-born after the year 2000. The possible determinants of disparities need be identified and investigated. PMID- 26153091 TI - Aging changes agonist induced contractile responses in permeabilized rat bladder. AB - Aging alters bladder functions where a decrease in filling, storage and emptying is observed. These changes cause urinary incontinence, especially in women. The aim of this study is to examine how aging affects the intracellular calcium movements due to agonist-induced contractions in permeabilized female rat bladder. Urinary bladder isolated from young and old female Sprague-Dawley rats were used. Small detrusor strips were permeabilized with beta-escin. The contractile responses induced with agonists were compared between young and old groups. Carbachol-induced contractions were decreased in permeabilized detrusor from old rats compared to young group. Heparin and ryanodine decreased carbachol induced contractions in young rats where only heparin inhibited these contractions in olds. Caffeine-induced contractions but not inositol triphosphate (IP3)-induced contractions were decreased in old group compared to youngs. The cumulative calcium response curves (pCa 8-4) were also decreased in old rats. Carbachol-induced calcium sensitization responses did not alter by age where GTP beta-S and GF-109203X but not Y-27632 inhibited these responses. Carbachol induced contractions decrease with aging in rat bladder detrusor. It can be postulated as IP3-induced calcium release (IICR) is primarily responsible for the contractions in older rats where the decrease in carbachol contractions in aging may be as a result of a decrease in calcium-induced calcium release (CICR), rather than carbachol-induced calcium sensitization. PMID- 26153092 TI - Graft arterial stenosis in kidney en bloc grafts from very small pediatric donors: incidence, timing, and role of ultrasound in screening. AB - In previous studies with different donor selection criteria and noncontemporary surgical techniques, graft arterial stenosis (GAS) has been reported to occur more frequently in adult recipients of pediatric en bloc renal allografts (EBKT) as compared to single adult donor allografts. The purpose of our study was to evaluate the incidence of GAS within our EBKT recipient population and to evaluate clinical and imaging features of those cases with GAS. In a retrospective cohort study, we analyzed 182 EBKT performed at a single institution. We identified cases of suspected GAS based on clinical factors, lab results, and noninvasive imaging. Diagnosis of GAS was confirmed by digital subtraction angiography. Two EBKT recipients (1.1% of 182) had angiographically confirmed GAS at 2.5 and 4.5 months after transplant. In both cases, the stenoses were short segment within the proximal (perianastomotic) donor aorta, color Doppler ultrasound demonstrated peak systolic velocities of >400 cm/s, and poststenotic parvus tardus waveforms were present. Both patients underwent angioplasty and demonstrated postintervention improvement in renal function and blood pressure. Restenosis did not occur during follow up. In conclusion, recipients of EBKT have a low incidence of GAS, similar to the lowest reported for adult single allografts. PMID- 26153093 TI - Role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma and the prognostic significance of C-reactive protein: A multi institutional, retrospective study. AB - OBJECTIVE: To analyze the role of adjuvant chemotherapy in lymph node-positive patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy, and identified the prognostic adjuvant chemotherapy parameters. METHODS: The clinicopathological records of 74 lymph node-positive upper tract urothelial carcinoma patients who underwent radical nephroureterectomy at multiple institutions were retrospectively reviewed. A total of 45 patients (60.8%) received adjuvant chemotherapy, and 29 (39.2%) underwent radical nephroureterectomy only. Kaplan-Meier analyses and Cox proportional hazard modeling were used to study the association between adjuvant chemotherapy status and both recurrence-free survival and cancer-specific survival. RESULTS: Estimated 5-year recurrence-free survival was 33.6% in patients undergoing radical nephroureterectomy plus adjuvant chemotherapy compared with 13.5% in patients undergoing radical nephroureterectomy only (hazard ratio 0.52; P = 0.014, log-rank test). Estimated 5-year cancer-specific survival was 42.5% in patients undergoing radical nephroureterectomy plus adjuvant chemotherapy, compared with 12.0% in patients undergoing radical nephroureterectomy only (hazard ratio 0.36; P = 0.0003, log-rank test). Multivariate analysis showed that adjuvant chemotherapy was a significant prognostic factor for cancer-specific survival (P = 0.001), but not for recurrence-free survival (P = 0.076). When patients undergoing radical nephroureterectomy plus adjuvant chemotherapy were dichotomized, based on preoperative C-reactive protein levels above or below the normal value, higher C reactive protein levels were significantly associated with poor survival (P = 0.012). CONCLUSION: Adjuvant chemotherapy seems to improve cancer-specific survival in lymph node-positive patients with upper tract urothelial carcinoma. Preoperative C-reactive protein levels could carry a prognostic value in this setting, and lymph node-positive patients with low preoperative CRP values should be considered for adjuvant chemotherapy. Further studies are necessary to validate these observations. PMID- 26153096 TI - Surgeon-estimated costs of common consumables in otolaryngology. AB - OBJECTIVES/HYPOTHESIS: The current fiscal climate demands increasing emphasis on curbing hospital expenses incurred from surgical procedures. Disposable instruments and consumables play a major role, but the end user (the surgeon) is often unaware of the cost of these materials. The objectives of our study were: 1) to assess knowledge of costs of disposable instruments and consumable products, and 2) to gauge interest in greater access to cost information and its potential to change practice. STUDY DESIGN: We used a cross-sectional survey study to meet our study's objectives. METHODS: A paper-based anonymous questionnaire was administered in the Department of Otolaryngology at McGill University and at Western University asking for estimations of costs of 23 commonly used products in the operating room. Our primary outcome measure was accuracy of cost estimations, which were considered accurate if within +/- 50% of the true cost at the respective institution. RESULTS: The average accuracy was 29.9% (standard deviation = 16.7%). There was no significant difference between residents (32.5%, 95% confidence interval [CI]: 10.2%-54.7%) and staff (28.3%, 95% CI: 11.0%-45.6%). Less than 10% of participants were able to accurately estimate the costs of at least half of the disposable products. The majority of participants (82%) felt that greater information would change their use of consumables. CONCLUSIONS: Surgical residents and staff have a generally poor knowledge of the cost of common consumable products used in the operating room. There is potential for increased awareness of costs to change behavior. LEVEL OF EVIDENCE: NA. PMID- 26153094 TI - Immune response and insulin signalling alter mosquito feeding behaviour to enhance malaria transmission potential. AB - Malaria parasites alter mosquito feeding behaviour in a way that enhances parasite transmission. This is widely considered a prime example of manipulation of host behaviour to increase onward transmission, but transient immune challenge in the absence of parasites can induce the same behavioural phenotype. Here, we show that alterations in feeding behaviour depend on the timing and dose of immune challenge relative to blood ingestion and that these changes are functionally linked to changes in insulin signalling in the mosquito gut. These results suggest that altered phenotypes derive from insulin signalling-dependent host resource allocation among immunity, blood feeding, and reproduction in a manner that is not specific to malaria parasite infection. We measured large increases in mosquito survival and subsequent transmission potential when feeding patterns are altered. Leveraging these changes in physiology, behaviour and life history could promote effective and sustainable control of female mosquitoes responsible for transmission. PMID- 26153097 TI - Accessibility needs and challenges of a mHealth system for patients with dexterity impairments. AB - : Purpose State: An innovative mobile health system called iMHere (interactive Mobile Health and Rehabilitation) has been developed at the University of Pittsburgh to support self-care and adherence to self-care regimens for patients with chronic conditions. The goal of this study is to explore and to identify the accessibility needs and preferences of individuals with dexterity impairments when they use the iMHere system. METHOD: Participants were asked to perform tasks after a one-week field trial. The time for a participant to complete each task, the number of possible errors a participant made and the number of errors a participant was able to self-correct were recorded and analyzed. The Telehealth Usability Questionnaire was collected to rate participants' experiences. RESULTS: Nine participants with various levels of dexterity abilities were included in the study. A statistically significant negative correlation was identified between participants' dexterity levels and their error ratios by using a Pearson product moment correlation (r = -0.434, n = 36, p = 0.004). Approximately 51% of errors detected was self-corrected without any help, but other errors called for resolution from a researcher. CONCLUSIONS: Due to the diversity of participants' dexterity impairments, their needs and preferences differ one from another. Personalized design may be the key to approaching these challenges in improving accessibility. Implications for Rehabilitation An innovative mobile health system called iMHere has been developed to support self-care and adherence to self-care regimens as part of rehabilitation for patients with chronic conditions. Before populations with these limitations can harness the potential of mHealth, accessibility of mHealth has to be addressed to ensure its quality and value. Dexterity limitations are commonly associated with chronic disease, accidents or aging. The study presented here identified the potential issues and barriers to accessibility related to user interface components for persons with dexterity impairments. The findings should be of interest for those working with mobile health, accessibility, smartphone apps, wellness and self-care. PMID- 26153098 TI - Arteriosclerosis and vascular calcification: causes, clinical assessment and therapy. AB - BACKGROUND: Arteriosclerosis is a pathological, structural (media vascular calcification) and physiological (modified vascular smooth vessel cells; increased arterial stiffness) alteration of the vessel wall. Through improved assessment methods (functional and imaging), it has become a well-known phenomenon in recent decades. However, its clinical importance was underestimated until recently. MATERIALS AND METHODS: Currently available English-speaking data about conditions/diseases associated with arteriosclerosis, its clinical sequels, available diagnostic procedures and therapeutic modalities were reviewed and summarized. RESULTS: In recent decades, emerging data have brought about a better understanding of causes and consequences of arteriosclerosis and highlight its growing clinical impact. CONCLUSION: Although arteriosclerosis showed an independent clinical impact on cardiovascular morbidity and mortality, especially in patients with chronic kidney disease/end-stage renal disease (CKD/ESRD) and diabetes mellitus, convincing clinical therapy concepts are not available until now. The establishment of novel therapeutic strategies derived from basic research is strongly needed. PMID- 26153099 TI - Quantitation of acotiamide in rat plasma by UHPLC-Q-TOF-MS: method development, validation and application to pharmacokinetics. AB - A novel, sensitive and selective ultra-high-performance liquid chromatography electrospray ionization mass spectrometry method was developed and validated for the quantification of acotiamide (ACT), a first-in-class drug used in functional dyspepsia, in rat plasma. A simple protein precipitation method with acetonitrile as precipitating solvent was used to extract ACT from rat plasma. ACT and an internal standard (mirabegron, IS) were separated on an Agilent poroshell EC C18 column (50 * 3.0 mm, 2.7 um) using methanol-10 mM ammonium acetate binary gradient mobile phase at a flow rate of 0.4 mL/min over 4 min run time. Detection was performed using target ions of [M + H](+) at m/z 451.2010 for ACT and m/z 397.1693 for IS in selective ion mode. The method was validated in the calibration range of 1.31-1000 ng/mL. All the validation parameters were well within the limits. The method demonstrated good performances in terms of intra- and inter-day precision (3.27-12.60% CV) and accuracy (87.96-104.94%). Thus the present ultra-high-pressure liquid chromatograhy-high-resolution mass spectrometry method for determination of ACT in rat plasma, is highly sensitive and rapid with a short run-time of 4 min, can be suitable for high sample throughput and for large batches of biological samples in pharmacokinetic studies. This method can be extended to measure plasma concentrations of ACT in humans to understand drug metabolism, drug interaction and adverse effects. PMID- 26153100 TI - Oscillations and Multiple Equilibria in Microvascular Blood Flow. AB - We investigate the existence of oscillatory dynamics and multiple steady-state flow rates in a network with a simple topology and in vivo microvascular blood flow constitutive laws. Unlike many previous analytic studies, we employ the most biologically relevant models of the physical properties of whole blood. Through a combination of analytic and numeric techniques, we predict in a series of two parameter bifurcation diagrams a range of dynamical behaviors, including multiple equilibria flow configurations, simple oscillations in volumetric flow rate, and multiple coexistent limit cycles at physically realizable parameters. We show that complexity in network topology is not necessary for complex behaviors to arise and that nonlinear rheology, in particular the plasma skimming effect, is sufficient to support oscillatory dynamics similar to those observed in vivo. PMID- 26153101 TI - Foetal tachyarrhythmia treatment remains challenging even if the vast majority of cases have a favourable outcome. AB - AIM: The optimal treatment for foetal tachyarrhythmia remains controversial, and this study aimed to fill this gap in the knowledge. METHODS: We retrospectively reviewed all cases of foetal tachyarrhythmia diagnosed at two tertiary foetal cardiology centres in Sweden from 1990 to 2012. RESULTS: Of the 153 cases, 28% had atrial flutter (AF), 63% had atrioventricular reentrant tachycardia (AVRT) and 9% had other mechanisms. Hydrops was present in 45, less frequently in AF than in AVRT. Transplacental treatment was commenced in 99 and the rhythm normalised in two-thirds, without any significant difference in cardioversion rates between AF and AVRT cases or nonhydropic and hydropic foetuses. Sotalol treatment had a higher cardioversion rate than digoxin in AVRT (63% versus 33%, p < 0.05) but not in AF (57% versus 56%). Two or more drugs were used in 38%. Neonatal survival was 100% in nonhydropic and 84% in hydropic cases. After a median of eight years, 11/134 patients still had arrhythmias, one had died due to arrhythmia and another had undergone cardiac transplantation. CONCLUSION: Transplacental treatment was frequently insufficient to obtain cardioversion in nonhydropic and hydropic foetuses, but all nonhydropic cases had favourable outcomes. Larger prospective studies are needed to optimise the treatment of cases with hydrops. PMID- 26153102 TI - A new CJASN series: renal immunology for the clinician. PMID- 26153103 TI - Kidney retransplantation in the ipsilateral iliac fossa: a surgical challenge. AB - The aim of this study is to review the surgical outcome of kidney retransplantation in the ipsilateral iliac fossa in comparison to first kidney transplants. The database was screened for retransplantations between 1995 and 2013. Each study patient was matched with 3 patients with a first kidney transplantation. Just for graft and patient survival analyses, we added an extra control group including all patients receiving a second transplantation in the contralateral iliac fossa. We identified 99 patients who received a retransplantation in the ipsilateral iliac fossa. There was significantly more blood loss and longer operative time in the retransplantation group. The rate of vascular complications and graft nephrectomies within 1 year was significantly higher in the study group. The graft survival rates at 1 year and 3, 5, and 10 years were 76%, 67%, 61%, and 47% in the study group versus 94%, 88%, 77%, and 67% (p < 0.001) in the first control group versus 91%, 86%, 78%, and 57% (p = 0.008) in the second control group. Patient survival did not differ significantly between the groups. Kidney retransplantation in ipsilateral iliac fossa is surgically challenging and associated with more vascular complications and graft loss within the first year after transplantation. Whenever feasible, the second renal transplant (first retransplant) should be performed contralateral to the prior failed one. PMID- 26153104 TI - Growth and reproduction of laboratory-reared neanurid Collembola using a novel slime mould diet. AB - Although significant progress has been made using insect taxa as model organisms, non-tracheated terrestrial arthropods, such as Collembola, are underrepresented as model species. This underrepresentation reflects the difficulty in maintaining populations of specialist Collembola species in the laboratory. Until now, no species from the family Neanuridae have been successfully reared. Here we use controlled growth experiments to provide explicit evidence that the species Neanura muscorum can be raised under laboratory conditions when its diet is supplemented with slime mould. Significant gains in growth were observed in Collembola given slime mould rather than a standard diet of algae-covered bark. These benefits are further highlighted by the reproductive success of the experimental group and persistence of laboratory breeding stocks of this species and others in the family. The necessity for slime mould in the diet is attributed to the 'suctorial' mouthpart morphology characteristic of the Neanuridae. Maintaining laboratory populations of neanurid Collembola species will facilitate their use as model organisms, paving the way for studies that will broaden the current understanding of the environmental physiology of arthropods. PMID- 26153106 TI - Cello-oligomer-binding dynamics and directionality in family 4 carbohydrate binding modules. AB - Carbohydrate-binding modules (CBMs) play significant roles in modulating the function of cellulases, and understanding the protein-carbohydrate recognition mechanisms by which CBMs selectively bind substrate is critical to development of enhanced biomass conversion technology. CBMs exhibit a limited range of specificity and appear to bind polysaccharides in a directional fashion dictated by the position of the ring oxygen relative to the protein fold. The two family 4 CBMs of Cellulomonas fimi Cel9B (CfCBM4) are reported to preferentially bind cellulosic substrates. However, experimental evidence suggests that these CBMs may not exhibit a thermodynamic preference for a particular orientation. We use molecular dynamics (MD) and free energy calculations to investigate protein carbohydrate recognition mechanisms in CfCBM4-1 and CfCBM4-2 and to elucidate preferential ligand-binding orientation. We evaluate four cellopentaose orientations including that of the crystal structure and three others suggested by nuclear magnetic resonance (NMR). These four orientations differ based on position of the ligand reducing end (RE) and pyranose ring orientations relative to the protein core. MD simulations indicate that the plausible orientations reduce to two conformations. Calculated ligand-binding free energy discerns each of the orientations is equally favorable. The calculated free energies are in excellent agreement with isothermal titration calorimetry measurements from the literature. MD simulations further reveal the approximate structural symmetry of the oligosaccharides relative to the amino acids along the binding cleft plays a role in the promiscuity of ligand binding. A survey of ligand-bound structures suggests this phenomenon may be characteristic of the broader class of proteins belonging to the beta-sandwich fold. PMID- 26153107 TI - Estimation of the Environmental Load of High- and Low-Density Polyethylene From South Korea Using a Mass Balance Approach. AB - The accumulation of marine plastic debris is one of the main emerging environmental issues of the twenty first century. Numerous studies in recent decades have reported the level of plastic particles on the beaches and in oceans worldwide. However, it is still unclear how much plastic debris remains in the marine environment because the sampling methods for identifying and quantifying plastics from the environment have not been standardized; moreover, the methods are not guaranteed to find all of the plastics that do remain. The level of identified marine plastic debris may explain only the small portion of remaining plastics. To perform a quantitative estimation of remaining plastics, a mass balance analysis was performed for high- and low-density PE within the borders of South Korea during 1995-2012. Disposal methods such as incineration, land disposal, and recycling accounted for only approximately 40 % of PE use, whereas 60 % remained unaccounted for. The total unaccounted mass of high- and low density PE to the marine environment during the evaluation period was 28 million tons. The corresponding contribution to marine plastic debris would be approximately 25,000 tons and 70 g km(-2) of the world oceans assuming that the fraction entering the marine environment is 0.001 and that the degradation half life is 50 years in seawater. Because the observed concentrations of plastics worldwide were much lower than the range expected by extrapolation from this mass balance study, it is considered that there probably is still a huge mass of unidentified plastic debris. Further research is therefore needed to fill this gap between the mass balance approximation and the identified marine plastics including a better estimation of the mass flux to the marine environment. PMID- 26153105 TI - Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis. AB - Neural stem cell (NSC)-based therapies offer potential for neural repair in central nervous system (CNS) inflammatory and degenerative disorders. Typically, these conditions present with multifocal CNS lesions making it impractical to inject NSCs locally, thus mandating optimization of vascular delivery of the cells to involved sites. Here, we analyzed NSCs for expression of molecular effectors of cell migration and found that these cells are natively devoid of E selectin ligands. Using glycosyltransferase-programmed stereosubstitution (GPS), we glycan engineered the cell surface of NSCs ("GPS-NSCs") with resultant enforced expression of the potent E-selectin ligand HCELL (hematopoietic cell E /L-selectin ligand) and of an E-selectin-binding glycoform of neural cell adhesion molecule ("NCAM-E"). Following intravenous (i.v.) injection, short-term homing studies demonstrated that, compared with buffer-treated (control) NSCs, GPS-NSCs showed greater neurotropism. Administration of GPS-NSC significantly attenuated the clinical course of experimental autoimmune encephalomyelitis (EAE), with markedly decreased inflammation and improved oligodendroglial and axonal integrity, but without evidence of long-term stem cell engraftment. Notably, this effect of NSC is not a universal property of adult stem cells, as administration of GPS-engineered mouse hematopoietic stem/progenitor cells did not improve EAE clinical course. These findings highlight the utility of cell surface glycan engineering to boost stem cell delivery in neuroinflammatory conditions and indicate that, despite the use of a neural tissue-specific progenitor cell population, neural repair in EAE results from endogenous repair and not from direct, NSC-derived cell replacement. PMID- 26153108 TI - Development of a cell-based qualitative assay for detection of neutralizing anti human interleukin-1 receptor antagonist (hIL-1Ra) antibodies in rats. AB - To determine the incidence of the positive neutralizing anti-human interleukin receptor antagonist (anti-IL-1Ra), a novel assay based on the proliferation of human melanoma A375.S2 cells was developed and validated. In the presence of a growth-limiting concentration of IL-1beta, A375.S2 cells were able to regain proliferation following the addition of IL-1Ra in a concentration-dependent manner. This dose-response effect enabled the validation of a standard curve for calculation of the concentration of IL-1Ra or, inversely, the concentration of neutralizing anti-IL-1Ra antibodies in cell culture medium or sera. The assay used CCK-8 as an indicator of proliferation. The dose-response relationship between rhIL-1Ra (dose range of 5-75 ng/ml rhIL-1Ra) and A375.S2 cell proliferation was sigmoidal and fitted a four-parameter logistic model. The percent coefficients of variation (%CVs) of quality control samples were 12.5 and 11.9% for intra-assay repeatability and 14.5 and 19.5% for inter-assay repeatability, while the total accuracy was in the range of 97.2-103.6%. For the neutralization assay, the optimal sample dilution factor was found to be 40-fold and the reasonable standard for positive and negative decision was calculated to be 59.4% neutralization rate. The %CVs of quality control samples were 12.7 and 24.0% for intra-assay repeatability and 11.6 and 30.0% for inter-assay repeatability. Analysis using the assay showed that rats could produce neutralizing anti-IL-1Ra antibodies after repeated intramuscular injection with rhIL-1Ra, and this response was not significantly dependent on the dose injected. PMID- 26153110 TI - Strategies used by individuals to prevent burnout. AB - BACKGROUND: Burnout represents a syndrome that is related to demanding job characteristics combined with the absence of resources or motivational job characteristics. The aim of this position study was to present strategies that individuals use to minimize burnout and its unfavourable effects. MATERIALS AND METHODS: The study focuses explicitly on strategies that individuals use to (i) deal with diminished resources that come with burnout, (ii) change their job characteristics such that the job becomes less demanding and more motivating and (iii) manage the interplay between the work and nonwork domains. RESULTS: Individuals seem to use coping, recovery and compensation strategies to reduce the impact of work stressors by changing the stressor or their responses to the stressor. Moreover, they use job crafting to alter the characteristics of the job such that it becomes less hindering and more motivating. Finally, individuals create boundaries between their work and nonwork domains to experience less work family and family-work conflicts by actively detaching from work. CONCLUSIONS: Finding bottom-up strategies that individuals use to minimize burnout or its unfavourable effects may be essential to complement the top-down interventions initiated by organizations. PMID- 26153109 TI - Cost of management in epistaxis admission: Impact of patient and hospital characteristics. AB - OBJECTIVES/HYPOTHESIS: To investigate patient and hospital characteristics associated with increased cost and length of stay in the inpatient management of epistaxis. STUDY DESIGN: Retrospective cross-sectional study of the 2008 to 2012 National (Nationwide) Inpatient Sample. METHODS: Patient and hospital characteristics of epistaxis admissions were analyzed. Multiple linear regression analysis was used to ascertain variables associated with increased cost and length of hospital stay. Variables significantly associated with high cost were further analyzed to determine the contribution of operative intervention and total procedures to cost. RESULTS: A total of 16,828 patients with an admitting diagnosis of epistaxis were identified. The average age was 67.5; 52.3% of the patients were male; 73.3% of the patients were Caucasian; and 70.7% of the hospital stays were government funded. The average length of stay was 3.24 days, and average hospitalization cost was $6,925. Longer length of stay was associated with black race, alcohol abuse, sinonasal disease, renal disease, Medicaid, and care at a northeastern U.S. hospital. Increased hospitalization costs of > $1,000 were associated with Asian/Pacific Islander race; sinonasal disease; renal disease; top income quartile; and care at urban teaching, northeastern, and western hospitals in the United States. High costs were predicted by procedural intervention in patients with comorbid alcohol abuse, sinonasal disease, renal disease, patients with private insurance, and patients managed at large hospitals. CONCLUSION: Although hospitalization costs are complex and multifactorial, we were able to identify patient and hospital characteristics associated with high costs in the management of epistaxis. Early identification and intervention, combined with implementation of targeted hospital management protocols, may improve outcomes and reduce financial burden. LEVEL OF EVIDENCE: 2C. PMID- 26153112 TI - Multicentre study of 18F-FDG-PET/CT prostate incidental uptake. AB - AIM: The purpose of our study was to establish the prevalence and pathological nature of fluorine-18-fluorodeoxyglucose (18F-FDG) prostate incidental uptake (PIU) among patients studied for non-prostate-malignant purposes in three nuclear medicine centres. METHODS: We retrospectively evaluated 20,422 scans performed on male patients; all patients underwent 18F-FDG-PET/CT for purposes not related to prostate disease. RESULTS: Among 20,422 patients PIU was identified for 280 (1.4 %) with an average age of 70 +/- 10.7 years. Sixty-three of the 280 patients with PIU (22.5 %) underwent PSA dosage and biopsy to determine the nature of the incidental uptake. Thirty-five of the 63 (55.5 %) PIU were malignant whereas 28/63 (44.5 %) were benign. The average value of PSA for patients with benign PIU was 3.7 +/- 2.8 ng/ml whereas it was 7.8 +/- 8.2 ng/ml in patients with malignant PIU; this difference was statistically significant. For malignant lesions, the average lesion-to-liver SUVmax ratio was 2.9 +/- 2.5 and the average lesion-to blood-pool SUVmax ratio was 3.7 +/- 2.5. For benign lesions, the average lesion to-liver SUVmax ratio was 2.5 +/- 1.7 and the average lesion-to-blood-pool SUVmax ratio was 3.5 +/- 2.4; there was no statistically significant difference between lesion-to-liver and lesion-to-blood-pool SUVmax ratios for benign and malignant lesions. CONCLUSION: Because PIU values are indicative of malignancy for a substantial percentage of patients, further investigation is required. PMID- 26153113 TI - Dissecting Attending Surgeons' Operating Room Guidance: Factors That Affect Guidance Decision Making. AB - PURPOSE: The amount of guidance provided by the attending surgeon in the operating room (OR) is a key element in developing residents' autonomy. The purpose of this study is to explore factors that affect attending surgeons' decision making regarding OR guidance provided to the resident. METHODS: We used video-stimulated recall interviews (VSRI) throughout this 2-phase study. In Phase 1, 3 attending surgeons were invited to review separately 30 to 45 minute video segments of their prerecorded surgical operations to explore factors that influenced their OR guidance decision making. In Phase 2, 3 attending surgeons were observed and documented in the OR (4 operations, 341min). Each operating surgeon reviewed their videotaped surgical performance within 5 days of the operation to reflect on factors that affected their decision making during the targeted guidance events. All VSRI were recorded. Thematic analysis and manual coding were used to synthesize and analyze data from VSRI transcripts, OR observation documents, and field notes. RESULTS: A total of 255 minutes of VSRI involving 6 surgeons and 7 surgical operations from 5 different procedures were conducted. A total of 13 guidance decision-making influence factors from 4 categories were identified (Cohen's kappa = 0.674): Setting (case schedule and patient morbidity), content (procedure attributes and case progress), resident (current competency level, trustworthiness, self-confidence, and personal traits), and attending surgeon (level of experience, level of comfort, preferred surgical technique, OR training philosophy, and responsibility as surgeon). A total of 5 factors (case schedule, patient morbidity, procedure attributes, resident current competency level, and trustworthiness) influenced attending surgeons' pre-OR guidance plans. "OR training philosophy" and "responsibility as surgeon" were anchor factors that affected attending surgeons' OR guidance decision-making patterns. CONCLUSIONS: Surgeons' OR guidance decision making is a dynamic process that is influenced by 13 situational factors. These factors can be used by residency programs to tailor strategies designed to increase resident autonomy in the OR. PMID- 26153114 TI - Evaluation of Sensory and Motor Skills in Neurosurgery Applicants Using a Virtual Reality Neurosurgical Simulator: The Sensory-Motor Quotient. AB - OBJECTIVE: Manual skill is an important attribute for any surgeon. Current methods to evaluate sensory-motor skills in neurosurgical residency applicants are limited. We aim to develop an objective multifaceted measure of sensory-motor skills using a virtual reality surgical simulator. DESIGN: A set of 3 tests of sensory-motor function was performed using a 3-dimensional surgical simulator with head and arm tracking, collocalization, and haptic feedback. (1) Trajectory planning: virtual reality drilling of a pedicle. Entry point, target point, and trajectory were scored-evaluating spatial memory and orientation. (2) Motor planning: sequence, timing, and precision: hemostasis in a postresection cavity in the brain. (3) Haptic perception: touching virtual spheres to determine which is softest of the group, with progressive difficulty. Results were analyzed individually and for a combined score of all the tasks. SETTING: The University of Chicago Hospital's tertiary care academic center. PARTICIPANTS: A total of 95 consecutive applicants interviewed at a neurosurgery residency program over 2 years were offered anonymous participation in the study; in 2 cohorts, 36 participants in year 1 and 27 participants in year 2 (validation cohort) agreed and completed all the tasks. We also tested 10 first-year medical students and 4 first- and second-year neurosurgery residents. RESULTS: A cumulative score was generated from the 3 tests. The mean score was 14.47 (standard deviation = 4.37), median score was 13.42, best score was 8.41, and worst score was 30.26. Separate analysis of applicants from each of 2 years yielded nearly identical results. Residents tended to cluster on the better performance side, and first-year students were not different from applicants. CONCLUSIONS: (1) Our cumulative score measures sensory-motor skills in an objective and reproducible way. (2) Better performance by residents hints at validity for neurosurgery. (3) We were able to demonstrate good psychometric qualities and generate a proposed sensory motor quotient distribution in our tested population. PMID- 26153115 TI - Determinants of the lethality of climate-related disasters in the Caribbean Community (CARICOM): a cross-country analysis. AB - Floods and storms are climate-related hazards posing high mortality risk to Caribbean Community (CARICOM) nations. However risk factors for their lethality remain untested. We conducted an ecological study investigating risk factors for flood and storm lethality in CARICOM nations for the period 1980-2012. Lethality- deaths versus no deaths per disaster event- was the outcome. We examined biophysical and social vulnerability proxies and a decadal effect as predictors. We developed our regression model via multivariate analysis using a generalized logistic regression model with quasi-binomial distribution; removal of multi collinear variables and backward elimination. Robustness was checked through subset analysis. We found significant positive associations between lethality, percentage of total land dedicated to agriculture (odds ratio [OR] 1.032; 95% CI: 1.013-1.053) and percentage urban population (OR 1.029, 95% CI 1.003-1.057). Deaths were more likely in the 2000-2012 period versus 1980-1989 (OR 3.708, 95% CI 1.615-8.737). Robustness checks revealed similar coefficients and directions of association. Population health in CARICOM nations is being increasingly impacted by climate-related disasters connected to increasing urbanization and land use patterns. Our findings support the evidence base for setting sustainable development goals (SDG). PMID- 26153116 TI - Low levels of mannose-binding lectin at admission increase the risk of adverse neurological outcome in preterm infants: a 1-year follow-up study. AB - OBJECTIVE: The aim of this study was to explore the association between serum levels of mannose-binding lectin (MBL) at admission and neurodevelopmental outcomes in a group of Chinese preterm infants, observed prospectively, until 1 year of corrected age (CA). METHODS: All preterm infants used in this study were received from the neonatal intensive care unit (NICU) of our Hospital between 1 January 2012 and 31 August 2013. Serum levels of MBL and clinical data were obtained at the time of admission. The influence of MBL levels on neurological outcome was assessed by logistic regression analysis. Clinical follow-up was performed at 1 year. RESULTS: The study cohort consisted of 175 neonates at baseline and 105 finished the 1-year follow-up. The mean serum MBL levels at the time of admission were significantly lower in children with adverse neurological outcomes as compared with children with no adverse [0.53 (SD = 0.09) MUg/ml versus 0.80 (SD = 0.17) MUg/ml, respectively; t = 8.342, p < 0.0001]. In multivariate analysis, there was an increased risk of adverse neurological outcomes associated with MBL <= 0.68 MUg/ml [odds ratios (OR) = 12.11, 95% confidence interval (CI): 2.31-30.32; p < 0.0001] after adjusting for possible factors. CONCLUSION: Preterm infants who had low levels of MBL at admission are exposed to an increased risk of adverse neurological outcomes. PMID- 26153117 TI - Helicobacter pylori, Chlamydiae pneumoniae and trachomatis as probable etiological agents of preeclampsia. AB - OBJECTIVES: The aim of this study was to evaluate the evidence for Helicobacter pylori, Chlamydiae pneumoniae and trachomatis to act as a probable etiology for preeclampsia (PE), together with estimating the prevalence of such infections in pregnant women with PE. METHODS: We performed a prospective study in Mansoura University Hospitals, Egypt, for detecting H. pylori infection by estimating H. pylori IgG and IgM, in addition to detection of Chlamydiae infections by PCR in 90 pregnant women with PE and 90 normotensive pregnant women of the same age and body mass index who were studied as control. RESULTS: The prevalence of H. pylori infection in preeclamptic pregnant women was 54.4% with a statistically significant association to PE. The prevalence of C. pneumonia was 27.8% whereas that of C. trachomatis was 4.44%. The infected preeclamptic cases showed high levels of leucocytes besides elevated C-reactive protein concentrations. CONCLUSION: Helicobacter pylori was found to act as a cofactor in the development of PE. Occurrence of C. trachomatis was low in pregnant women in our community; however, it showed that it may act as a cofactor in PE, whereas C. pneumoniae was attributed to have no role in PE pathogenesis until supported by further studies. PMID- 26153118 TI - Prominent coronary artery flow with normal coronary artery anatomy is a rare but ominous harbinger of poor outcome in the fetus. AB - OBJECTIVES: "Heart sparing" refers to prominent antegrade fetal coronary artery (CA) blood flow readily visualized by color Doppler and is a harbinger of poor outcome in growth restricted fetus, but little is known of the features and presentation of heart sparing in normally grown fetuses. Our objective was to describe heart sparing effects in normally grown fetuses, and compare the presentation and outcome of heart sparing between fetuses with growth restriction and those who were normally grown. METHODS: In a series of fetuses with prominent antegrade CA flow, we assessed Doppler flow profiles in the aortic isthmus, ductus venosus (DV), umbilical vein (UV), umbilical artery (UA) and middle cerebral artery (MCA). We calculated MCA and UA systolic/diastolic ratios and the cerebral placental ratio, and measured fetal biometry. We evaluated cardiac function using the myocardial performance index (MPI) and the cardiovascular profile score (CVPS). RESULTS: Ten fetuses with heart sparing had normal DV flow at 24-36.6 (mean 30.9) weeks of gestation. Five had growth restriction (Group 1); 4/5 had normal MPI and CVPS, and one died. Five were normally grown (Group 2); 5/5 had elevated MPI and decreased CVPS, of these 2 died in utero and one died immediately after birth despite urgent delivery. Coronary arteries were normal after birth or autopsy. CONCLUSIONS: Heart sparing confers a poor prognosis in fetal growth restriction and in normally grown fetuses with cardiac dysfunction. We suggest CA flow be assessed in all high-risk fetuses. PMID- 26153119 TI - Low-density subculture: a technical note on the importance of avoiding cell-to cell contact during mesenchymal stromal cell expansion. AB - Numerous scientific studies and clinical trials are carried out each year exploring the use of mesenchymal stromal cells in regenerative medicine and tissue engineering. However, the effective and reliable expansion of this very important cell type remains a challenge. In this study the importance of cell-to cell contact during expansion has been explored on the proliferation and differentiation potential of the produced cells. Cells were cultured up to passage 5 under conditions where cell-to-cell contact was either probable (40-70% confluence; see supporting information, Protocol A) or where it was unlikely (10 50% confluence; see supporting information, Protocol B). The effect of the two different conditions on expansion efficiency; proliferation rate and tri-lineage differentiation potential was assessed. Differences in immunophenotype, cell size and senescence were also investigated. Protocol B cultures expanded twice as fast as those cultured with Protocol A. In passage 5 experiments low confluence expanded cells displayed a 10% higher overall proliferation rate, and produced 23% more cells in growth, 12% more in osteogenic, 77% more in adipogenic, but 27% less in chondrogenic medium. Differentiation potential wasn't decisively affected at the mRNA level. However, Protocol B favoured bone and cartilage differentiation at the secretional level. Protocol A populations showed reduced purity, expressing CD105 in only 76% compared to the 96.7% in Protocol B cultures. Protocol A populations also contained significantly more (+4.2%) senescent cells, however, no difference was found in cell size between the two protocols. The findings of this study suggest that cell-to-cell contact, and therefore high confluence levels, is detrimental to MSC quality. PMID- 26153120 TI - Impact of three different mouthwashes on the incidence of gingival overgrowth induced by cyclosporine-A: a randomized controlled experimental animal study. AB - OBJECTIVE: This study aimed to evaluate the effects of three different mouthwashes on the incidence of cyclosporine-A-induced gingival overgrowth. STUDY DESIGN: One hundred albino rats were divided into five equal groups. Group I rats received no treatment. Group II rats were administered cyclosporine-A. Group III, IV, and V rats were handled as group II and concomitantly treated with chlorhexidine gluconate, cetylpyridinium chloride, and essential oil mouthwashes, respectively. Ten rats from each group were euthanized after the first week of treatment, and the remaining rats were euthanized after the second week of treatment. The obtained specimens were stained with hematoxylin and eosin, Masson's trichrome, and tumor growth factor beta (TGF-beta), matrix metalloproteinase 1 (MMP-1), and interleukin 6 (IL-6) immunohistochemical stains. RESULTS: The histologic findings at the end of the first and second weeks revealed marked increases in gingival overgrowth for groups II and IV in comparison with groups III and V. Increased epithelial thickness and collagen accumulation were prominent in groups II and IV compared with the other groups. Groups II and IV revealed the highest immunoreactivities for TGF-beta and for IL 6. Groups I, III, and V revealed the highest level of MMP-1 expression. CONCLUSIONS: Essential oils and chlorhexidine gluconate mouthwashes significantly reduced the incidence of gingival overgrowth compared with cetylpyridinium chloride. PMID- 26153121 TI - Haem uptake is essential for egg production in the haematophagous blood fluke of humans, Schistosoma mansoni. AB - Schistosomes ingest host erythrocytes, liberating large quantities of haem. Despite its toxicity, haem is an essential factor for numerous biological reactions, and may be an important iron source for these helminths. We used a fluorescence haem analogue, palladium mesoporphyrin, to investigate pathways of haem acquisition, and showed that palladium mesoporphyrin accumulates in the vitellaria (eggshell precursor glands) and ovary of female Schistosoma mansoni. Furthermore, incubation of adult females in 10-100 MUm cyclosporin A (IC50 = 2.3 MUm) inhibits the uptake of palladium mesoporphyrin to these tissues, with tenfold reductions in fluorescence intensity of the ovary. In vitro exposure to cyclosporin A resulted in significant perturbation of egg production, reducing egg output from 34 eggs per female to 5.7 eggs per female over the incubation period, and retardation of egg development. We characterized a S. mansoni homologue of the haem-responsive genes of Caenorhabditis elegans. The gene (Smhrg 1) encodes a protein with a molecular weight of approximately 17 kDa. SmHRG-1 was able to rescue growth in haem transport-deficient HEM1Delta yeast. Transcriptional suppression of Smhrg-1 in adult S. mansoni worms resulted in significant delay in egg maturation, with 47% of eggs from transcriptionally suppressed worms being identified as immature compared with only 27% of eggs laid by control worms treated with firefly luciferase. Our findings indicate the presence of transmembrane haem transporters in schistosomes, with a high abundance of these molecules being present in tissues involved in oogenesis. PMID- 26153122 TI - Assaying Carcinoembryonic Antigens by Normalized Saturation Magnetization. AB - Biofunctionalized magnetic nanoparticles (BMNs) that provide unique advantages have been extensively used to develop immunoassay methods. However, these developed magnetic methods have been used only for specific immunoassays and not in studies of magnetic characteristics of materials. In this study, a common vibration sample magnetometer (VSM) was used for the measurement of the hysteresis loop for different carcinoembryonic antigens (CEA) concentrations (Phi CEA) based on the synthesized BMNs with anti-CEA coating. Additionally, magnetic parameters such as magnetization (M), remanent magnetization (M R), saturation magnetization (M S), and normalized parameters (DeltaM R/M R and DeltaM S/M S) were studied. Here, DeltaM R and DeltaM s were defined as the difference between any Phi CEA and zero Phi CEA. The parameters M, DeltaM R, and DeltaM S increased with Phi CEA, and DeltaM S showed the largest increase. Magnetic clusters produced by the conjugation of the BMNs to CEAs showed a DeltaM S greater than that of BMNs. Furthermore, the relationship between DeltaM S/M S and Phi CEA could be described by a characteristic logistic function, which was appropriate for assaying the amount of CEAs. This analytic DeltaM S/M S and the BMNs used in general magnetic immunoassays can be used for upgrading the functions of the VSM and for studying the magnetic characteristics of materials. PMID- 26153123 TI - Multicolor Photodetector of a Single Er(3+)-Doped CdS Nanoribbon. AB - Er(3+)-doped CdS nanoribbons (Er-CdS NRs) are synthesized by thermal evaporation and then characterized by field emission scanning electron microscopy (FE-SEM), high-resolution transmission electron microscopy (HRTEM), photoluminescence (PL), and absorption spectra. The Er-CdS NR photodetector is studied systematically, including spectral response, light intensity response, and photoconductance (G) versus temperature (T). It is found that Er-CdS NR has the ability of detecting multicolor light including blue, red, and near-infrared light with higher responsivity (R lambda ) and external quantum efficiency (eta). The conductance of Er-CdS NR under dark conditions decreases with increasing temperature in the range of 87-237 K, while its conductance increases with increasing temperature in the range of 237-297 K when T is larger than 237 K. These results indicated that ionized impurities and the intrinsic excitation are responsible for the conductance change of Er-CdS NR in the dark. The superior performance of the Er CdS NR device offers an avenue to develop highly sensitive multicolor photodetector applications. PMID- 26153124 TI - Light Trapping Enhancement in a Thin Film with 2D Conformal Periodic Hexagonal Arrays. AB - Applying a periodic light trapping array is an effective method to improve the optical properties in thin-film solar cells. In this work, we experimentally and theoretically investigate the light trapping properties of two-dimensional periodic hexagonal arrays in the framework of a conformal amorphous silicon film. Compared with the planar reference, the double-sided conformal periodic structures with all feature periodicities of sub-wavelength (300 nm), mid wavelength (640 nm), and infrared wavelength (2300 nm) show significant broadband absorption enhancements under wide angles. The films with an optimum periodicity of 300 nm exhibit outstanding antireflection and excellent trade-off between light scattering performance and parasitic absorption loss. The average absorption of the optimum structure with a thickness of 160 nm is 64.8 %, which is much larger than the planar counterpart of 38.5 %. The methodology applied in this work can be generalized to rational design of other types of high performance thin-film photovoltaic devices based on a broad range of materials. PMID- 26153125 TI - Preparation of Core-Shell Hybrid Materials by Producing a Protein Corona Around Magnetic Nanoparticles. AB - Nanoparticles experience increasing interest for a variety of medical and pharmaceutical applications. When exposing nanomaterials, e.g., magnetic iron oxide nanoparticles (MNP), to human blood, a protein corona consisting of various components is formed immediately. The composition of the corona as well as its amount bound to the particle surface is dependent on different factors, e.g., particle size and surface charge. The actual composition of the formed protein corona might be of major importance for cellular uptake of magnetic nanoparticles. The aim of the present study was to analyze the formation of the protein corona during in vitro serum incubation in dependency of incubation time and temperature. For this, MNP with different shells were incubated in fetal calf serum (FCS, serving as protein source) within a water bath for a defined time and at a defined temperature. Before and after incubation the particles were characterized by a variety of methods. It was found that immediately (seconds) after contact of MNP and FCS, a protein corona is formed on the surface of MNP. This formation led to an increase of particle size and a slight agglomeration of the particles, which was relatively constant during the first minutes of incubation. A longer incubation (from hours to days) resulted in a stronger agglomeration of the FCS incubated MNP. Quantitative analysis (gel electrophoresis) of serum-incubated particles revealed a relatively constant amount of bound proteins during the first minutes of serum incubation. After a longer incubation (>20 min), a considerably higher amount of surface proteins was determined for incubation temperatures below 40 degrees C. For incubation temperatures above 50 degrees C, the influence of time was less significant which might be attributed to denaturation of proteins during incubation. Overall, analysis of the molecular weight distribution of proteins found in the corona revealed a clear influence of incubation time and temperature on corona composition. PMID- 26153126 TI - Analyzing Arabidopsis thaliana root proteome provides insights into the molecular bases of enantioselective imazethapyr toxicity. AB - Imazethapyr (IM) is a widely used chiral herbicide that inhibits the synthesis of branched-chain amino acids (BCAAs). IM is thought to exert its toxic effects on amino acid synthesis mainly through inhibition of acetolactate synthase activity, but little is known about the potential effects of IM on other key biochemical pathways. Here, we exposed the model plant Arabidospsis thaliana to trace S- and R-IM enantiomer concentrations and examined IM toxicity effects on the root proteome using iTRAQ. Conventional analyses of root carbohydrates, organic acids, and enzyme activities were also performed. We discovered several previously unknown key biochemical pathways targeted by IM in Arabidospsis. 1,322 and 987 proteins were differentially expressed in response to R- and S-IM treatments, respectively. Bioinformatics and physiological analyses suggested that IM reduced the BCAA tissue content not only by strongly suppressing BCAA synthesis but also by increasing BCAA catabolism. IM also affected sugar and starch metabolism, changed the composition of root cell walls, increased citrate production and exudation, and affected the microbial community structure of the rhizosphere. The present study shed new light on the multiple toxicity mechanisms of a selective herbicide on a model plant. PMID- 26153127 TI - Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD. AB - BACKGROUND AND OBJECTIVES: CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m(2) for >=3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006. RESULTS: Plasma sCD14 was negatively associated with eGFR (rho=-0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (rho=-0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up. CONCLUSIONS: Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis. PMID- 26153128 TI - Predictors of Atrasentan-Associated Fluid Retention and Change in Albuminuria in Patients with Diabetic Nephropathy. AB - BACKGROUND AND OBJECTIVES: Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention. RESULTS: Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases in Hb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb. CONCLUSIONS: In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention. PMID- 26153129 TI - Mining microbial metatranscriptomes for expression of antibiotic resistance genes under natural conditions. AB - Antibiotic resistance genes are found in a broad range of ecological niches associated with complex microbiota. Here we investigated if resistance genes are not only present, but also transcribed under natural conditions. Furthermore, we examined the potential for antibiotic production by assessing the expression of associated secondary metabolite biosynthesis gene clusters. Metatranscriptome datasets from intestinal microbiota of four human adults, one human infant, 15 mice and six pigs, of which only the latter have received antibiotics prior to the study, as well as from sea bacterioplankton, a marine sponge, forest soil and sub-seafloor sediment, were investigated. We found that resistance genes are expressed in all studied ecological niches, albeit with niche-specific differences in relative expression levels and diversity of transcripts. For example, in mice and human infant microbiota predominantly tetracycline resistance genes were expressed while in human adult microbiota the spectrum of expressed genes was more diverse, and also included beta-lactam, aminoglycoside and macrolide resistance genes. Resistance gene expression could result from the presence of natural antibiotics in the environment, although we could not link it to expression of corresponding secondary metabolites biosynthesis clusters. Alternatively, resistance gene expression could be constitutive, or these genes serve alternative roles besides antibiotic resistance. PMID- 26153130 TI - Deficits of olfactory interneurons in polysialyltransferase- and NCAM-deficient mice. AB - The neurogenic niche of the anterior subventricular zone (SVZ) persistently generates neuroblasts, which migrate along the rostral migratory stream (RMS) into the olfactory bulb (OB), where they differentiate into granule and periglomerular cells. Loss of the neural cell adhesion molecule NCAM or its post translational modification polysialic acid (polySia) impairs migration causing accumulations of cells in the proximal RMS and decreased OB volume. Polysialylation of NCAM is implemented by two polysialyltransferases, ST8SIA2 and ST8SIA4, with overlapping functions. Here, we used mice with Ncam1 and polysialyltransferase deletions to analyze how partial or complete loss of polySia synthesis or a combined loss of polySia and NCAM affects the RMS and the interneuron composition in the OB. Numerous calretinin (CR)-positive cells were detected dispersed around the RMS in Ncam1 knockout, St8sia2, St8sia4 double knockout, and St8sia2, St8sia4, Ncam1 triple-knockout mice, as well as in St8sia2(-/-) but not in St8sia4(-/-) mice. These changes were not reflected by reductions of CR-positive cells in the granule or glomerular layer of the OB. Instead, calbindin-positive periglomerular interneurons were strongly reduced in all polySia-NCAM negative mice and slightly attenuated in St8sia2(-/-) as well as in the St8sia4(-/-) mice, which were devoid of ectopic CR-positive cells along the RMS. Consistent with the early developmental generation of calbindin- as compared with CR-positive OB interneurons, this phenotype was fully developed at postnatal day 5. Together, these results demonstrate that the early development of calbindin-positive periglomerular interneurons depends on the presentation of polySia on NCAM and requires the activity of both polysialyltransferases. PMID- 26153131 TI - Leptin promotes human endometriotic cell migration and invasion by up-regulating MMP-2 through the JAK2/STAT3 signaling pathway. AB - Despite evidence that leptin may play a role in the pathogenesis of endometriosis, the specific function of leptin in the migration and invasion of endometriotic cells is not well characterized. In this study, we investigated the effect of leptin on the migration, invasion and matrix metalloproteinase (MMP) expression levels of human endometriotic cells. We found that leptin stimulated the migration and invasion of endometriotic cells (11Z, 12Z and 22B) in a dose dependent manner. Leptin receptor (ObR) siRNA significantly inhibited the migration and invasion induced by leptin in 11Z and 12Z cells. Leptin-induced migration and invasion were significantly attenuated by pretreatment with SB-3CT, a specific gelatinase (MMP-2 and MMP-9) inhibitor. In addition, leptin-induced increases in the mRNA and protein expression and enzyme activity of MMP-2 in 11Z and 12Z cells. Selectively inhibiting MMP-2 using siRNA and an inhibitor (GM6003), impaired the ability of leptin to stimulate the migration and invasion of endometriotic cells, suggesting that MMP-2 plays an essential role in leptin induced migration and invasion. Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) inhibitor (AG490) significantly inhibited the migration, invasion and MMP-2 expression induced by leptin in endometriotic cells. Furthermore, the Extracellular signal-Regulated Kinase inhibitor PD98059 neutralized the migration and invasion promoting effects of leptin. Taken together, these results suggest that leptin may contribute to the migration and invasion abilities of endometriotic cells via the up-regulation of MMP-2 through an ObR-dependent JAK2/STAT3 signaling pathway. PMID- 26153132 TI - Novel characterization of the HSPA2-stabilizing protein BAG6 in human spermatozoa. AB - While a large cohort of sperm surface receptors underpin sperm-oocyte adhesion processes, our recent work has revealed that the molecular chaperone Heat Shock Protein A2 (HSPA2) is a key regulator of zona pellucida-receptor complex assembly in our own species. Indeed, in the infertile population, spermatozoa that fail to interact with the zona pellucida of the oocyte consistently lack HSPA2 protein expression. While the mechanisms behind this protein deficiency are under consideration, BCL2-associated athanogene 6 (BAG6) has been identified as a key regulator of HSPA2 stability in mouse germ cells. However, in the human, the presence of BAG family proteins remains completely uncharacterized. Consequently, this study aimed to determine the presence of BAG6 in human sperm cells and to characterize its putative interaction with HSPA2 throughout sperm cell development. BAG6 was shown to co-localize with HSPA2 in human testicular germ cells and epididymal spermatozoa. Similarly, BAG6 was identified in the equatorial region of non-capacitated spermatozoa but underwent a marked relocation to the anterior region of the head upon the induction of capacitation in these cells. Protein-protein interaction assays revealed the stable interaction of BAG6 and HSPA2 proteins in mature spermatozoa. Furthermore, examination of the spermatozoa of infertile men with zona pellucida binding defects, related to a lack of HSPA2, revealed a concomitant deficiency in BAG6 protein expression. In view of the findings described in this study, we propose that BAG6 is likely a key regulator of HSPA2 stability/function in human germ cells. Moreover, its under-representation in spermatozoa with zona pellucida binding deficiency suggests that BAG6 may be an important candidate to study for a further understanding of male idiopathic infertility. PMID- 26153133 TI - Eccentric apical hypertrophic cardiomyopathy unmasked by multimodality imaging: an uncommon but missed cause of out of hospital cardiac arrest. AB - A woman in her late 50s experienced a witnessed, sudden out of hospital cardiac arrest. Initial workup included coronary angiography, transthoracic echocardiogram and a CT scan of the chest to rule out pulmonary embolus. She was subsequently discharged home without an implantable cardioverter defibrillator (ICD) or a life vest. On follow-up at another facility, an ICD was placed and a Holter monitor showed no ventricular ectopy. Further transthoracic echocardiographic images were obtained, which were suggestive of apical hypertrophic cardiomyopathy. A limited transthoracic echocardiogram with contrast was performed, which did not elucidate the hypertrophy. However, eccentric left ventricular apical wall hypertrophy was visualised by a coronary CT scan. PMID- 26153134 TI - The Forbidden Quantum Adder. AB - Quantum information provides fundamentally different computational resources than classical information. We prove that there is no unitary protocol able to add unknown quantum states belonging to different Hilbert spaces. This is an inherent restriction of quantum physics that is related to the impossibility of copying an arbitrary quantum state, i.e., the no-cloning theorem. Moreover, we demonstrate that a quantum adder, in absence of an ancillary system, is also forbidden for a known orthonormal basis. This allows us to propose an approximate quantum adder that could be implemented in the lab. Finally, we discuss the distinct character of the forbidden quantum adder for quantum states and the allowed quantum adder for density matrices. PMID- 26153135 TI - Automated 3-dimensional morphologic analysis of sputum specimens for lung cancer detection: Performance characteristics support use in lung cancer screening. AB - BACKGROUND: The LuCED Lung Test comprises an automated 3-dimensional morphologic analysis of epithelial cells in sputum. For each cell, 594 morphology-based features are measured to drive algorithmic classifiers that quantitatively assess whether neoplastic cells are present. The current interim clinical study involves sputum samples from patients with known benign and malignant outcomes to assess the feasibility of LuCED as an adjunctive test after suspicious low-dose computed tomography (LDCT) results or as an independent screening test for lung cancer. METHODS: Sputum samples were fixed, enriched for epithelial cells, and analyzed with a 3-dimensional cell scanner called Cell-CT. Candidate abnormal cells were identified by the classifiers for manual review. The sensitivity, specificity, and negative and positive predictive values were calculated for the detection of neoplastic cases. RESULTS: A total of 91 sputum samples from patients with confirmed lung cancer (49 patients) and patients with no known malignancy (42 patients) were evaluated. After cytology review, sensitivity in the positive group was 91.8%, and specificity was 95.2%. Specificity was not 100% because there were 2 cases in which abnormal cells were identified by the Cell-CT that were confirmed as such at the time of manual cytology review. However, at the time of last follow-up, malignancy had not been detected in these 2 cases. Modeling in a population with a 1% prevalence of lung cancer, the positive and negative predictive values would be 95.4% and 99.9%, respectively. CONCLUSIONS: LuCED testing is highly sensitive and specific for the detection of lung cancer and has potential value as an adjunctive test after suspicious LDCT findings or as a primary screening test in which LuCED-positive cases would be triaged to diagnostic CT. Further prospective studies currently are underway to evaluate its full usefulness. PMID- 26153136 TI - Targeting cancer cells in the tumor microenvironment: opportunities and challenges in combinatorial nanomedicine. AB - Cancer therapies of the future will rely on synergy between drugs delivered in combination to achieve both maximum efficacy and decreased toxicity. Nanoscale drug delivery vehicles composed of highly tunable nanomaterials ('nanocarriers') represent the most promising approach to achieve simultaneous, cell-selective delivery of synergistic ratios of combinations of drugs within solid tumors. Nanocarriers are currently being used to co-encapsulate and deliver synergistic ratios of multiple anticancer drugs to target cells within solid tumors. Investigators exploit the unique environment associated with solid tumors, termed the tumor microenvironment (TME), to make 'smart' nanocarriers. These sophisticated nanocarriers exploit the pathological conditions in the TME, thereby creating highly targeted nanocarriers that release their drug payload in a spatially and temporally controlled manner. The translational and commercial potential of nanocarrier-based combinatorial nanomedicines in cancer therapy is now a reality as several companies have initiated human clinical trials. PMID- 26153137 TI - EpiFactors: a comprehensive database of human epigenetic factors and complexes. AB - Epigenetics refers to stable and long-term alterations of cellular traits that are not caused by changes in the DNA sequence per se. Rather, covalent modifications of DNA and histones affect gene expression and genome stability via proteins that recognize and act upon such modifications. Many enzymes that catalyse epigenetic modifications or are critical for enzymatic complexes have been discovered, and this is encouraging investigators to study the role of these proteins in diverse normal and pathological processes. Rapidly growing knowledge in the area has resulted in the need for a resource that compiles, organizes and presents curated information to the researchers in an easily accessible and user friendly form. Here we present EpiFactors, a manually curated database providing information about epigenetic regulators, their complexes, targets and products. EpiFactors contains information on 815 proteins, including 95 histones and protamines. For 789 of these genes, we include expressions values across several samples, in particular a collection of 458 human primary cell samples (for approximately 200 cell types, in many cases from three individual donors), covering most mammalian cell steady states, 255 different cancer cell lines (representing approximately 150 cancer subtypes) and 134 human postmortem tissues. Expression values were obtained by the FANTOM5 consortium using Cap Analysis of Gene Expression technique. EpiFactors also contains information on 69 protein complexes that are involved in epigenetic regulation. The resource is practical for a wide range of users, including biologists, pharmacologists and clinicians. PMID- 26153138 TI - Proton-Detected Solid-State NMR Spectroscopy of Bone with Ultrafast Magic Angle Spinning. AB - While obtaining high-resolution structural details from bone is highly important to better understand its mechanical strength and the effects of aging and disease on bone ultrastructure, it has been a major challenge to do so with existing biophysical techniques. Though solid-state NMR spectroscopy has the potential to reveal the structural details of bone, it suffers from poor spectral resolution and sensitivity. Nonetheless, recent developments in magic angle spinning (MAS) NMR technology have made it possible to spin solid samples up to 110 kHz frequency. With such remarkable capabilities, (1)H-detected NMR experiments that have traditionally been challenging on rigid solids can now be implemented. Here, we report the first application of multidimensional (1)H-detected NMR measurements on bone under ultrafast MAS conditions to provide atomistic-level elucidation of the complex heterogeneous structure of bone. Our investigations demonstrate that two-dimensional (1)H/(1)H chemical shift correlation spectra for bone are obtainable using fp-RFDR (finite-pulse radio-frequency-driven dipolar recoupling) pulse sequence under ultrafast MAS. Our results infer that water exhibits distinct (1)H-(1)H dipolar coupling networks with the backbone and side chain regions in collagen. These results show the promising potential of proton detected ultrafast MAS NMR for monitoring structural and dynamic changes caused by mechanical loading and disease in bone. PMID- 26153140 TI - Identification of three PPV1 VP2 protein-specific B cell linear epitopes using monoclonal antibodies against baculovirus-expressed recombinant VP2 protein. AB - Porcine parvovirus type 1 (PPV1) is a major causative agent of embryonic and fetal death in swine. The PPV1 VP2 protein is closely associated with viral immunogenicity for eliciting neutralizing antibodies, but its antigenic structures have been largely unknown. We generated three monoclonal antibodies (MAbs) against baculovirus-expressed recombinant PPV1 VP2 protein. A PEPSCAN analysis identified the minimal B cell linear epitopes of PPV1 VP2 based on these MAbs. Three core epitopes, (228)QQITDA(233), (284)RSLGLPPK(291), and (344)FEYSNGGPFLTPI(356), were defined and mapped onto three-dimensional models of the PPV1 virion and VP2 monomer. The epitope (228)QQITDA(233) is exposed on the virion surface, and the other two are located inside the protein. An alignment of the PPV1 VP2 amino acid sequences showed that (284)RSLGLPPK(291) and (344)FEYSNGGPFLTPI(356) are absolutely conserved, whereas (228)QQITDA(233) has a single substitution at residue 233 in some (S -> A or T). We developed a VP2 epitope-based indirect enzyme-linked immunosorbent assay (iELISA) to test for anti-PPV1 antibodies. In a comparative analysis with an immunoperoxidase monolayer assay using 135 guinea pig sera, the VP2-epitope-based iELISA had a concordance rate of 85.19 %, sensitivity of 83.33 %, and specificity of 85.47 %. MAb 8H6 was used to monitor VP2 during the PPV1 replication cycle in vitro with an indirect immunofluorescence assay, which indicated that newly encapsulated virions are released from the nucleus at 24 h postinfection and the PPV1 replication cycle takes less than 24 h. This study provides valuable information clarifying the antigenic structure of PPV1 VP2 and lays the foundations for PPV1 serodiagnosis and antigen detection. PMID- 26153139 TI - The substrate tolerance of alcohol oxidases. AB - Alcohols are a rich source of compounds from renewable sources, but they have to be activated in order to allow the modification of their carbon backbone. The latter can be achieved via oxidation to the corresponding aldehydes or ketones. As an alternative to (thermodynamically disfavoured) nicotinamide-dependent alcohol dehydrogenases, alcohol oxidases make use of molecular oxygen but their application is under-represented in synthetic biotransformations. In this review, the mechanism of copper-containing and flavoprotein alcohol oxidases is discussed in view of their ability to accept electronically activated or non-activated alcohols and their propensity towards over-oxidation of aldehydes yielding carboxylic acids. In order to facilitate the selection of the optimal enzyme for a given biocatalytic application, the substrate tolerance of alcohol oxidases is compiled and discussed: Substrates are classified into groups (non-activated prim and sec-alcohols; activated allylic, cinnamic and benzylic alcohols; hydroxy acids; sugar alcohols; nucleotide alcohols; sterols) together with suitable alcohol oxidases, their microbial source, relative activities and (stereo)selectivities. PMID- 26153141 TI - Engineering immunity in the mucosal niche against sexually transmitted infections. AB - The mucosal surfaces of the genital tract are the site of entry to over 30 different bacterial, parasitic, and viral pathogens that are the cause of sexually transmitted infections (STIs) including HIV. Women and adolescent girls are more severely impacted by STIs than men due in part to a greater biological susceptibility for acquiring infections and differences in disease sequelae. While it is widely accepted that preventative vaccines against the most commonly transmitted STIs would have a major impact on decreasing the global health burden of STIs for women worldwide, several challenges preclude their development. The female genital tract is a complex niche of microflora, hormonal influences, and immune tissues and cells that result in a mucosal immune system that is distinct from other mucosal sites and from our systemic immune system. An appreciation of these differences and their effect on shaping mucosal immunity to sexually transmitted pathogens is an important determinant for the design of effective STI vaccines. Here we describe the anatomy and mucosal immune system of the female reproductive tract, and discuss bioengineering strategies to design mucosal vaccines that overcome delivery challenges and coordinate the presentation kinetics and compartmentalization of antigens and adjuvants to relevant mucosal immune cell subsets. In particular, we describe recent progress in understanding the role of specific mucosal dendritic cell subsets in facilitating immune responses to pathogenic microbes in the genital mucosa. We also discuss the development of pathogen-mimicking materials that may be useful for engineering protective immunity in this mucosal niche. PMID- 26153142 TI - Intra-arterial thrombolysis of central retinal artery occlusion following percutaneous atrial septal defect closure. AB - Use of percutaneous devices for atrial septal defect (ASD) closure is growing, given the minimally invasive nature and the long-term durability of this approach. The reported rate of thrombus formation after catheter closure is 1.2%. Thrombotic risk varies according to closure device and Dacron-covered nitinol Amplatzer devices carry a 0-0.3% rate of thrombus formation; but central retinal artery occlusion (CRAO) is rarely implicated as an adverse event. Herein, we report the first successful intra-arterial thrombolytic treatment of CRAO developing after ASD closure via Amplatzer device. (c) 2015 Wiley Periodicals, Inc. PMID- 26153144 TI - Continuous cyclohexane oxidation to cyclohexanol using a novel cytochrome P450 monooxygenase from Acidovorax sp. CHX100 in recombinant P. taiwanensis VLB120 biofilms. AB - The applications of biocatalysts in chemical industries are characterized by activity, selectivity, and stability. One key strategy to achieve high biocatalytic activity is the identification of novel enzymes with kinetics optimized for organic synthesis by Nature. The isolation of novel cytochrome P450 monooxygenase genes from Acidovorax sp. CHX100 and their functional expression in recombinant Pseudomonas taiwanensis VLB120 enabled efficient oxidation of cyclohexane to cyclohexanol. Although initial resting cell activities of 20 U gCDW (-1) were achieved, the rapid decrease in catalytic activity due to the toxicity of cyclohexane prevented synthetic applications. Cyclohexane toxicity was reduced and cellular activities stabilized over the reaction time by delivering the toxic substrate through the vapor phase and by balancing the aqueous phase mass transfer with the cellular conversion rate. The potential of this novel CYP enzyme was exploited by transferring the shake flask reaction to an aqueous-air segmented flow biofilm membrane reactor for maximizing productivity. Cyclohexane was continuously delivered via the silicone membrane. This ensured lower reactant toxicity and continuous product formation at an average volumetric productivity of 0.4 g L tube (-1) h(-1) for several days. This highlights the potential of combining a powerful catalyst with a beneficial reactor design to overcome critical issues of cyclohexane oxidation to cyclohexanol. It opens new opportunities for biocatalytic transformations of compounds which are toxic, volatile, and have low solubility in water. PMID- 26153143 TI - Compound 331 selectively induces glioma cell death by upregulating miR-494 and downregulating CDC20. AB - Malignant gliomas are the most common malignant tumors in the central nervous system (CNS). Up to date, the prognosis of glioma is still very poor, effective therapy with less side-effect is very necessary. Herein, we identify a compound named as "331" selectively induced cell death in glioma cells but not in astrocytes. Compound 331 upregulated miR-494 and downregulated CDC20 in glioma cells but not in astrocytes. These results suggest that compound 331 could be a potential drug selectively targeting glioma cells through upregulating miR-494 and downregulating CDC20. PMID- 26153145 TI - A pilot study imaging integrin alphavbeta3 with RGD PET/CT in suspected lung cancer patients. AB - PURPOSE: Angiogenesis is an essential step in tumour development and metastasis. Integrin alphavbeta3 plays a major role in angiogenesis, tumour growth and progression. A new tracer, (18)F-AL-NOTA-PRGD2, denoted as (18)F-alfatide, has been developed for positron emission tomography (PET) imaging of integrin alphavbeta3. This is a pilot study to test the safety and diagnostic value of (18)F- arginine-glycine-aspartic acid (RGD) PET/computed tomography (CT) in suspected lung cancer patients. METHODS: Twenty-six patients with suspected lung cancer on enhanced CT underwent (18)F-alfatide RGD PET/CT examination before surgery and puncture biopsy. Standard uptake values (SUVs) and the tumour-to blood ratios were measured, and diagnoses were pathologically confirmed. RESULTS: RGD PET/CT with (18)F-alfatide was performed successfully in all patients and no clinically significant adverse events were observed. The (18)F-alfatide RGD PET/CT analysis correctly recognized 17 patients with lung cancer, 4 patients (hamartoma) as true negative, and 5 patients (4 chronic inflammation and 1 inflammatory pseudotumour) as false positive. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of (18)F-alfatide RGD PET/CT for the diagnosis of suspected lung cancer patients was 100, 44.44, 80.77, 77.27, and 100%, respectively. The area under a receiver operating characteristic (ROC) curve was 0.75 (P = 0.038), and ROC analysis suggested an SUVmax cut-off value of 2.65 to differentiate between malignant lesions and benign lesions. The SUV for malignant lesions was 5.37 +/- 2.17, significantly higher than that for hamartomas (1.60 +/- 0.11; P < 0.001). The difference between the tumour-to-blood ratio for malignant lesions (4.13 +/- 0.91) and tissue of interest-to-blood ratio for hamartomas (1.56 +/- 0.24) was also statistically significant (P < 0.001). Neither the SUVmax nor the tumour-to blood ratio was significantly different between malignant lesions and inflammatory lesions or inflammatory pseudotumours (P > 0.05). Sixteen of 26 patients later underwent successful surgery, and pathologic examination confirmed nodes positive for metastasis in 14 of 152 lymph nodes. The sensitivity, specificity, accuracy, PPV, and NPV of PET/CT for lymph nodes was 92.86, 95.65, 95.40, 61.90, and 99.25%, respectively. CONCLUSION: Our results suggest that RGD PET/CT with the new tracer (18)F-alfatide is safe and potentially effective in the diagnosis of non-small cell lung cancer. It may be used in the diagnosis of lung cancer, successfully distinguishing malignant lesions from hamartoma. However, it is difficult to clearly differentiate inflammatory or inflammatory pseudotumours from malignant lesions. Additional studies with a larger number of patients are needed to validate our findings. PMID- 26153147 TI - Precipitation deficits increase high diurnal temperature range extremes. AB - The relationship between precipitation deficits and extreme hot temperatures has been documented in observation and modeling studies. However, it is unclear whether and how increases in maximum temperatures will impact diurnal temperature range (DTR) extremes. Here, we used observational data sets from meteorological stations in China to examine the trends in high DTR extremes from 1971 to 2013, represented by the percentage of high DTR days (%HDD) and maximum high DTR duration (MHDD), as well as their relationships with precipitation deficits over the past four decades in China. We identified both positive and negative trends in the %HDD and MHDD in China during each season, implying an inhomogeneous behavior of DTR and DTR extremes. Furthermore, we observed a significant negative relationship between precipitation deficits and the %HDD and MHDD during each season, and the relationship was strongest in the summer. The statistical analysis of this coupled behavior indicated that precipitation deficits were related to an increase in high DTR extremes, with a 22% average higher probability of the occurrence of DTR extremes after dry conditions than wet conditions in the summer. Knowledge from this study has important implications for interpreting climate anomalies. PMID- 26153146 TI - iROLL: does 3-D radioguided occult lesion localization improve surgical management in early-stage breast cancer? AB - PURPOSE: To prospectively evaluate the feasibility of 3-D radioguided occult lesion localization (iROLL) and to compare iROLL with wire-guided localization (WGL) in patients with early-stage breast cancer undergoing breast-conserving surgery and sentinel lymph node biopsy (SLNB). METHODS: WGL (standard procedure) and iROLL in combination with SLNB were performed in 31 women (mean age 65.1 +/- 11.2 years) with early-stage breast cancer and clinically negative axillae. Patient comfort in respect of both methods was assessed using a ten point scale. SLNB and iROLL were guided by freehand SPECT (fhSPECT). The results of the novel 3-D image-based method were compared with those of WGL, ultrasound-based lesion localization, and histopathology. RESULTS: iROLL successfully detected the malignant primary and at least one sentinel lymph node in 97% of patients. In a single patient (3%), only iROLL, and not WGL, enabled lesion localization. The variability between fhSPECT and ultrasound-based depth localization of breast lesions was low (1.2 +/- 1.4 mm). Clear margins were achieved in 81% of the patients; however, precise prediction of clear histopathological surgical margins was not feasible using iROLL. Patients rated iROLL as less painful than WGL with a pain score 0.8 +/- 1.2 points (p < 0.01) lower than the score for iROLL. CONCLUSION: iROLL is a well-tolerated and feasible technique for localizing early stage breast cancer in the course of breast-conserving surgery, and is a suitable replacement for WGL. As a single image-based procedure for localization of breast lesions and sentinel nodes, iROLL may improve the entire surgical procedure. However, no advantages of the image-guided procedure were found with regard to prediction of complete tumour resection. PMID- 26153148 TI - Shape of the Osseous External Auditory Canal and Its Relationship to Troublesome Cavities. AB - OBJECTIVES/HYPOTHESIS: On the basis of clinical observations, the shape of the osseous external auditory canal (OEAC) has often been seen as an etiological factor in troublesome cavities after modified radical mastoidectomy. STUDY DESIGN: Retrospective analysis of CT scans. METHODS: To assess the role of the shape of the OEAC in troublesome modified radical cavities using computed tomographic scans of three groups of patients (without pathology and with or without draining cavities), we determined the depth of the pretympanic recess (DPTR) and its anterior curvature (ACPTR). In addition to looking at the shape of the OEAC, we also studied the role of any remaining mastoid air cells in relation to troublesome radical cavities, as well as the consultation frequency. RESULTS: The DPTR was significantly deeper in draining cavities than in ears without pathology and dry cavities. No difference in the ACPTR was observed. The presence of remaining mastoid air cells is significantly associated with the presence of a troublesome radical cavity. CONCLUSIONS: The shape of the OEAC (i.e., the DPTR) is a contributory factor to the drainage of modified radical cavities. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:693-698, 2016. PMID- 26153149 TI - How morphology influences relaxivity - comparative study of superparamagnetic iron oxide-polymer hybrid nanostructures. AB - Superparamagnetic iron oxides (SPIOs) are widely used in MRI as T2 contrast agents, and interest is still growing. Here, the T2 relaxivity of three different SPIO-polymer hybrid morphologies, i.e. homogeneously distributed iron oxide within a polymer matrix, Janus-like nanoparticles and polymer nanocapsules containing iron oxides, is studied. Making use of calculations based on theory for agglomerated systems, the obtained T2 values could be predicted for all different morphologies, except for nanocapsules. Nanocapsules, in contrast to full spheres, allow for water exchange between encapsulated water and bulk water, and thus have two contributions to relaxivity. One originates from the capsules acting as a weakly magnetized cluster and the other stems from the individual SPIOs inside the capsule. Therefore, the relaxivities were also computed using an empirical equation found in the literature, which considers water exchange, resulting in a better T2 forecast for the nanocapsules. The presented study is the first example of a comparison between measured and calculated relaxivities of nanocapsules. PMID- 26153150 TI - Promise and peril: Dissemination of findings from studies of drugs used in pregnancy and their association with birth defects. AB - BACKGROUND: When and how to publish birth defects research can be complex, especially in the context of drugs used in pregnancy. Such research frequently involves multiple stakeholders, including regulatory agencies. Researchers must balance the potential peril of an unnecessarily panicked populace versus the benefit of protecting the public's health. METHODS: We use a case presentation and contemporary literature to highlight the potential tradeoffs that researchers must consider. We highlight important considerations including the public health impact, examining the likelihood of causality, understanding common considerations when using large data sources, the role of peer review and working in partnership with regulatory agencies. RESULTS: We suggest that plans for analyses, dissemination and risk communication are done best a priori and not post hoc. CONCLUSION: Rigorous research evaluating the impact of drugs used in pregnancy, coupled with effective dissemination strategies, has the potential improve outcomes for mothers and their infants for generations. PMID- 26153151 TI - MicroRNA-34c-5p is related to recurrence in laryngeal squamous cell carcinoma. AB - OBJECTIVES/HYPOTHESIS: Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival. STUDY DESIGN: Retrospective cohort study. METHODS: Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. RESULTS: A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR 34c-5p expression was associated with an increased risk of recurrence. CONCLUSIONS: A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences. LEVEL OF EVIDENCE: NA. PMID- 26153152 TI - MR tracking of SPIO-labeled mesenchymal stem cells in rats with liver fibrosis could not monitor the cells accurately. AB - Our previous study showed that in vivo magnetic resonance (MR) imaging is effective in tracking superparamagnetic iron oxide (SPIO)-labeled bone marrow mesenchymal stem cells (BMSCs) in rats with liver fibrosis. SPIO-labeling-induced signal reduction on MR images was completely reversed within 15 days after transplantation. It is still unclear whether the signal changes in MR imaging could reflect the number of transplanted cells in the liver. In the present study, BMSCs of male rats were doubly labeled with enhanced green fluorescent protein (EGFP) and SPIO and injected intravascularly into female rats with liver fibrosis. At different time points after injection, MR imaging was performed. The distribution of SPIO particles and EGFP-positive cells was determined by Prussian blue staining and EGFP immunohistochemistry, respectively. The distribution of transplanted BMSCs in various organs was assessed by detection of the SRY gene using real-time quantitative PCR. At 15 days post transplantation, the numbers of transplanted cells were significantly decreased in the lung, kidney, spleen and muscle, but not liver and heart, in comparison with those at 7 days after transplantation. EGFP staining-positive cells were observed in the liver intralobular parenchyma, while Prussian blue staining was negative at 42 days after transplantation. Taken together, SPIO particles and EGFP-labeled BMSCs show a different tissue distribution pattern in rats with liver fibrosis after a long term period of monitoring. SPIO-based MR imaging may not be suitable for long term tracking of transplanted BMSCs in vivo. PMID- 26153153 TI - Intra-Rater Reliability of Rehabilitative Ultrasound Imaging for Multifidus Muscles Thickness and Cross Section Area in Healthy Subjects. AB - INTRODUCTION: Rehabilitative Ultrasound Imaging (RUSI) must be valuable method for research and rehabilitation. So, the reliability of its measurements must be determined. The purpose of this study was to evaluate the intra-rater reliability of RUSI for measurement of multifidus (MF) muscles cross section areas (CSAs), bladder wall diameter, and thickness of MF muscles between 2 sessions in healthy subjects. METHOD: Fifteen healthy subjects through simple non-probability sampling participated in this single-group repeated-measures reliability study. MF muscles thickness at rest and during contraction, MF muscles CSAs at rest, and bladder diameters at rest and during pelvic floor muscles (PFM) contraction were measured through RUSI. Pearson's correlation coefficient test was used to determine intra-rater reliability of variables. FINDING: The results showed that intra-class correlation Coefficient (ICCs) values with 95% confidence interval (CI) and the standard error of the measurement (SEM) were good to excellent agreement for a single investigator between measurement occasions. The intra rater reliability for the bladder wall displacement was high (ICCs for rest and PFM contraction state: 0.96 and 0.95 respectively), for the MF muscles CSAs at the L4 level was good to high (ICCs 0.75 and 0.91 for right (Rt) and left (Lt) side respectively), and for the thickness of MF muscles at two levels, at rest and during two tasks was moderate to high (ICCs: 0.64 to 0.87). CONCLUSION: The Trans-Abdominal (TA) method of RUSI is a reliable method to quantify the PFM contraction in healthy subjects. Also, the RUSI is a reliable method to measure the MF muscles CSAs, the MF muscles thickness at rest and during functional tasks in healthy subjects. PMID- 26153154 TI - The Hurt of Judgment in Excessive Weight Women: A Hermeneutic Study. AB - Excess weight is one of the increasing problems of the present society and one of the threatening health conditions around the world. Despite many efforts for prevention and treatment or even surgery, the process of excess weight is not decreased in the world. While most of the studies conducted on excess weight concentrated on the issues why people get excess weight or how the prevention and treatment of excess weight must be performed, there is lake of knowledge about what excessive weight people really experience in their daily life. Understanding the lived experience of excess weight in women is linked with their health and society's health while it indirectly develops the nursing knowledge to improve the quality and access to holistic health care in excessive weight women. The aim of study was to describe with a deeper understanding, the lived experience of excess weight in women. Using a hermeneutic phenomenological approach and a van manen analysis methods, in depth semi- structured interviews were conducted with twelve women who had lived experience of excess weight. The hurt of Judgment was the main theme that emerged in the process of data analysis. This theme was derived from three sub-themes including social judgment, being different and being seen. These findings can prove helpful in promoting the nursing knowledge concerning a holistic approach in communicating to excessive weight people. PMID- 26153155 TI - Asymmetric Information in Iranian's Health Insurance Market: Testing of Adverse Selection and Moral Hazard. AB - BACKGROUND: Asymmetric information is one of the most important issues in insurance market which occurred due to inherent characteristics of one of the agents involved in insurance contracts; hence its management requires designing appropriate policies. This phenomenon can lead to the failure of insurance market via its two consequences, namely, adverse selection and moral hazard. OBJECTIVE: This study was aimed to evaluate the status of asymmetric information in Iran's health insurance market with respect to the demand for outpatient services. MATERIALS/PATIENTS AND METHODS: This research is a cross sectional study conducted on households living in Iran. The data of the research was extracted from the information on household's budget survey collected by the Statistical Center of Iran in 2012. In this study, the Generalized Method of Moment model was used and the status of adverse selection and moral hazard was evaluated through calculating the latent health status of individuals in each insurance category. To analyze the data, Excel, Eviews and stata11 software were used. RESULTS: The estimation of parameters of the utility function of the demand for outpatient services (visit, medicine, and Para-clinical services) showed that households were more risk averse in the use of outpatient care than other goods and services. After estimating the health status of households based on their health insurance categories, the results showed that rural-insured people had the best health status and people with supplementary insurance had the worst health status. In addition, the comparison of the conditional distribution of latent health status approved the phenomenon of adverse selection in all insurance groups, with the exception of rural insurance. Moreover, calculation of the elasticity of medical expenses to reimbursement rate confirmed the existence of moral hazard phenomenon. CONCLUSIONS: Due to the existence of the phenomena of adverse selection and moral hazard in most of health insurances categories, policymakers need to adjust contracts so that to reduce these phenomena. Given the importance of financing, the presence of such problems can lead to less coverage of health insurance provided by insurers, loss of contracts with health care institutions and service providers, and lower quality of health services. PMID- 26153156 TI - Utilization and Cost of Health Services in Individuals With Traumatic Brain Injury. AB - Traumatic Brain Injury (TBI) has gained attention in the past decade as a "signature injury" in the conflicts in Iraq and Afghanistan. TBI is a major burden for both the military and civilian population in the US and worldwide. It is a leading cause of death and disability in the US and a major health services resource burden. We seek to answer two questions. What is the evidence regarding the association of TBI with health services utilization and costs in the US and worldwide? What is the evidence regarding racial/ethnic, gender, geographic, socio-economic and other disparities in health services utilization and cost in the US and worldwide? To attain this goal we searched several databases using key words to perform a systematic review of the literature since 2000. We found 36 articles to be eligible for inclusion in the review. The evidence demonstrates a wide variation in health services utilization and costs depending on population of study and severity of TBI. The evidence also supports the existence of racial/ethnic, gender, insurance, geographic disparities in the US as well as other unique disparities worldwide. PMID- 26153157 TI - Comparison Patients and Staffs Satisfaction in General Versus Special Wards of Hospitals of Jahrom. AB - INTRODUCTION AND AIMS: Patient satisfaction is the most important indicator of high-quality health care and is used for the assessment and planning of health care. Also, Job satisfaction is an important factor on prediction and perception of organizational manner. The aim of this study is to identify and compare patient and staff satisfaction in general versus special wards. MATERIAL AND METHOD: In order to identify the various indicators of satisfaction and dissatisfaction, a descriptive study (cross sectional) was done to assess patients' satisfaction with in-patient care at Jahrom University of Medical Science hospitals. The sample size was 600 patients that selected by sequential random sampling technique and are close to their discharge from the hospital. Patients were asked to indicate the scale point which best reflected their level of satisfaction with the treatment or service. Also we assess the staff satisfaction (sample size was 408 staffs) in general ward using a researcher made questionnaire. It should be noted that the participants were anonymous and there was no obligation to participation. We tried to set a secure and comfortable environment for filling out the questionnaire. RESULTS: Among 600 patients, 239 (n=38.67%) were men and 368 (61.33%) were female. Number of nurses was 408, of which 135 (33.08%) were men and 273 (66.92%) female. There was a significant correlation between working experience and professional factors of personnel. The mean total patient satisfaction in general and special wards is (2.75+/-.35, 3.03+/-.53) respectively. Differences of patient satisfaction in domains such respect, care and confidence in general wards versus special ward were statistically significant, but there was no difference in expect time of patients in these wards. Differences Between the mean patient and staff satisfaction in the general wards versus special wards were statistically significant using independent t-tests (p=.018, p=.029). Spearman test showed a statistically significant correlation between patient and staff satisfaction (p=.044). CONCLUSION: For improving quality of medical services and effective functioning needs maximizing efforts to obtain full patient and staff satisfaction. PMID- 26153158 TI - Clinical Interdisciplinary Collaboration Models and Frameworks From Similarities to Differences: A Systematic Review. AB - INTRODUCTION: So far, various models of interdisciplinary collaboration in clinical nursing have been presented, however, yet a comprehensive model is not available. The purpose of this study is to review the evidences that had presented model or framework with qualitative approach about interdisciplinary collaboration in clinical nursing. METHODS: All the articles and theses published from 1990 to 10 June 2014 which in both English and Persian models or frameworks of clinicians had presented model or framework of clinical collaboration were searched using databases of Proquest, Scopus, pub Med, Science Direct, and Iranian databases of Sid, Magiran, and Iranmedex. In this review, for published articles and theses, keywords according with MESH such as nurse-physician relations, care team, collaboration, interdisciplinary relations and their Persian equivalents were used. RESULTS: In this study contexts, processes and outcomes of interdisciplinary collaboration as findings were extracted. One of the major components affecting on collaboration that most of the models had emphasized was background of collaboration. Most of studies suggested that the outcome of collaboration were improved care, doctors and nurses' satisfaction, controlling costs, reducing clinical errors and patient's safety. CONCLUSION: Models and frameworks had different structures, backgrounds, and conditions, but the outcomes were similar. Organizational structure, culture and social factors are important aspects of clinical collaboration. So it is necessary to improve the quality and effectiveness of clinical collaboration these factors to be considered. PMID- 26153159 TI - Sesame Lignans and Vitamin E Supplementation Improve Subjective Statuses and Anti Oxidative Capacity in Healthy Humans With Feelings of Daily Fatigue. AB - Sesamin has anti-oxidative functions in vivo. Fatigue is caused in part by oxidative stress. We evaluated whether sesame lignans (sesamin/episesamin=1/1, 10 mg) with vitamin E (55 mg of alpha-tocopherol) (SVE) could improve subjective statuses and anti-oxidative capacity in humans using questionnaires on fatigue, sleep and physical appearance, as well as low-density lipoprotein oxidation lag time. A placebo-controlled, double-blind, parallel-group study was conducted with subjects experiencing daily fatigue. After a run-in period, subjects were administered oral SVE or a placebo (P) for 8 weeks. A questionnaire regarding fatigue, sleep and physical appearance was conducted at 0, 4, and 8 weeks. Plasma low-density lipoprotein oxidation lag time was measured as an indicator of anti oxidative capacity. The per-protocol analysis revealed significant improvements in fatigue status at 4 and 8 weeks compared to 0 weeks in both groups (p<0.01), and sleep and physical appearance at 8 weeks compared to 0 weeks only in the SVE group (p<0.01). There were no significant differences observed between the groups. According to the 72-subject subgroup analysis (aged 40 and over), the sleep and physical appearance significantly improved compared to the P group (p<0.05), and fatigue status showed a tendency for improvement compared to the P group. Anti-oxidative capacity in the SVE group significantly increased compared to the P group (p<0.01). No adverse events relating to SVE supplementation were confirmed. These results suggest SVE supplementation could safely alleviate daily fatigue and oxidative stress. PMID- 26153160 TI - Barriers to Effective Doctor-Patient Relationship Based on PRECEDE PROCEED Model. AB - OBJECTIVE: This study intends to investigate interns and faculty members' insights into constructing relationship between physicians and patients at 3 more accredited Iranian universities of medical sciences. METHOD: Applying PRECEDE PROCEED model, semi-structured interviews were completed with 7 interns and 14 faculty members and two themes were emerged from directed content analysis. The meaning units of the first theme, barriers to effective doctor-patient relationship, are discussed in this paper. RESULTS: According to the participants, building doctor-patient relationship is influenced by many contextual and regulatory factors as well as content, process and perceptual skills of physicians. CONCLUSIONS: Faculty and curriculum development, as well as foundation of the department of communication skills at medical schools are recommended to eliminate the impact of poor communication on patients' satisfaction and physicians' self-efficacy specific to their communication skills. PRACTICE IMPLICATIONS: Applying theories and models of health education and health promotion, researchers and educators can use the most predictive constructs of theories to design and implement effective interventions. PMID- 26153161 TI - Diagnosis of Malignancy in Thyroid Tumors by Multi-Layer Perceptron Neural Networks With Different Batch Learning Algorithms. AB - To diagnose the malignancy in thyroid tumor, neural network approach is applied and the performances of thirteen batch learning algorithms are investigated on accuracy of the prediction. Therefore, a back propagation feed forward neural networks (BP FNNs) is designed and three different numbers of neuron in hidden layer are compared (5, 10 and 20 neurons). The pathology result after the surgery and clinical findings before surgery of the patients are used as the target outputs and the inputs, respectively. The best algorithm(s) is/are chosen based on mean or maximum accuracy values in the prediction and also area under Receiver Operating Characteristic Curve (ROC curve). The results show superiority of the network with 5 neurons in the hidden layer. In addition, the better performances are occurred for Polak-Ribiere conjugate gradient, BFGS quasi-newton and one step secant algorithms according to their accuracy percentage in prediction (83%) and for Scaled Conjugate Gradient and BFGS quasi-Newton based on their area under the ROC curve (0.905). PMID- 26153162 TI - A Comparative Study of Survival Rate in High Grade Glioma Tumors Being Treated by Radiotherapy Alone Versus Chemoradiation With Nitrosourea. AB - BACKGROUND: In adults, malignant glioma (high-grade glioma) is one of the most common brain tumors. In spite of different types of treatment, the outcome is still not likely to be favorable. The aim of this study was to determine the difference between survival rate in adult patients with high grade glioma treated by radiotherapy only and those treated by a combination of radiotherapy and nitrosurea-based chemotherapy. METHODS: This study was conducted using the records of 48 patients with grade 3 or 4 of glial brain tumor referred to the radiation-oncology ward of Shohada-e-Tajrish Hospital in Tehran, Iran from 2005 to 2012. The patients had undergone radiotherapy alone or adjuvant chemoradiation with nitrosourea. The median survival of patients after receiving the different types of treatment were evaluated using the Kaplan-Meier method and the log -rank exam. Data were analyzed using univariate analysis for median survival regarding to the patients' age, gender, extent of surgery, Karnofsky performance status (KPS) with the Kaplan-Meier method, and the log-rank exam. We used the Cox-model for multivariate analysis. RESULTS: Records of 48 patients were studied (34 men and 14 women). The mean survival were 18 months for men and 15.2 months for women (P=0.05). Around 58% (28 patients) were more than 50 years old, and 42% (20 patients) were less than 50, and mean survival for the two age groups were 13 and 20 months, respectively (P<0.001). Then, the patients were divided into three groups according to the extent of surgery, i.e., excisional biopsy (11 patients), stereotactic biopsy (22 patients), and resection (15 patients), and the mean survival for the three groups were 14.7, 17.3, and 18.8 months, respectively. There was no significant statistical difference for mean survival between the three groups (P=0.23). The KPS was greater than 70% in 23 patients and less than 70% in 21 patients, and the mean survival for the former and latter groups were 17.6 and 16 months, respectively (P=0.67), four patients had unknown KPS. Twenty patients received only radiotherapy, and chemoradiation was done for 28 patients, and the mean survival for the former and latter patients were 14.5 and 19 months, respectively (P=0.15). CONCLUSION: In this study, we concluded that age was the only effective factor in the survival of the patients and that chemotherapy had no significant effect on the survival of the patients. PMID- 26153163 TI - Regional Decentralisation in the Greek Health Care System: Rhetoric and Reality. AB - Decentralisation is a complex, yet basic feature of health care systems in many countries entailing the transfer of authority or dispersal of power in public planning, management and decision making from higher to lower levels of government. This paper describes the attempts made in Greece from 1923 until today to decentralise its highly centralised health care system, drawing on a thorough documentary analysis of legislative acts and official reports regarding regional health policy. The analysis shows that, although decentralisation has been attempted on several occasions, in the end it was abandoned every time. The first ever implementation of a decentralised system of governance in 2001 was also curtailed, resulting in only minor decentralisation of authority and real powers. It is suggested that decentralisation has been impeded by many factors, especially obstruction by opposition from key interest groups, absence of policy continuity between governments, the inability to tackle the bureaucratic and highly centralised system and lack of political will. PMID- 26153164 TI - Application of Texture Analysis in Diagnosis of Multiple Sclerosis by Magnetic Resonance Imaging. AB - INTRODUCTION: Visual inspection by magnetic resonance (MR) images cannot detect microscopic tissue changes occurring in MS in normal appearing white matter (NAWM) and may be perceived by the human eye as having the same texture as normal white matter (NWM). The aim of the study was to evaluate computer aided diagnosis (CAD) system using texture analysis (TA) in MR images to improve accuracy in identification of subtle differences in brain tissue structure. MATERIAL & METHODS: The MR image database comprised 50 MS patients and 50 healthy subjects. Up to 270 statistical texture features extract as descriptors for each region of interest. The feature reduction methods used were the Fisher method, the lowest probability of classification error and average correlation coefficients (POE+ACC) method and the fusion Fisher plus the POE+ACC (FFPA) to select the best, most effective features to differentiate between MS lesions, NWM and NAWM. The features parameters were used for texture analysis with principle component analysis (PCA) and linear discriminant analysis (LDA). Then first nearest neighbour (1-NN) classifier was used for features resulting from PCA and LDA. Receiver operating characteristic (ROC) curve analysis was used to examine the performance of TA methods. RESULTS: The highest performance for discrimination between MS lesions, NAWM and NWM was recorded for FFPA feature parameters using LDA; this method showed 100% sensitivity, specificity and accuracy and an area of Az=1 under the ROC curve. CONCLUSION: TA is a reliable method with the potential for effective use in MR imaging for the diagnosis and prediction of MS. PMID- 26153165 TI - Factors Associated with Anger among Male Adolescents in Western Iran: An Application of Social Cognitive Theory. AB - INTRODUCTION: Anger can be defined a natural emotional response that is gradually formed to protect us in dealing with threats, damages, assaults, and failures; while hatred is a change of attitude which is built following the persistence of anger towards a subject or an individual. One of the main reasons of adolescents' reference to the counseling centers is their anger accompanied by violence. OBJECTIVE: This study aims to determine the social cognitive factors associated with anger among a population of adolescents in the west of Iran based on the social cognitive theory. METHODOLOGY: Samples were selected based on multi-stage cluster sampling. Method including the first and the second-grade male high school students from Ilam town (N=360). The Spielberger's anger questionnaire (STAXI 2) and a self-designed questionnaire based on Bandura's social cognitive theory were employed as the data collection instruments in the present study. RESULTS: Of the selected population, 200 students were the first-grade and 160 students were the second-grade students. 135 students were the first child of the family, 150 students were the second or the third birth, and 75 students were the fifth or above in their families. Descriptive tests and correlation analysis were used to conduct the statistical analysis. Although there was a significant and inverse relationship between all the components of the theory and anger, the strongest relationship was seen in self-efficacy (-0.585) and the weakest relationship was seen in modeling (-0.297). DISCUSSION & CONCLUSION: If was concluded that helping people to know their abilities and have a better personal judgment in this case, can influence their anger control. In addition, the process of stress management can effectively increase an individual's emotional coping. PMID- 26153166 TI - Sexual Satisfaction Concept Analysis in Iranian Married Women: A Hybrid Model Study. AB - BACKGROUND: Sexual satisfaction is considered to be a sexual right and an important component of sexual health. The purpose of this qualitative study was to clarify the meaning and the nature of sexual satisfaction in Iranian married women, and to provide a cultural-based definition of it. METHOD: Sexual satisfaction was examined in three phases by the Hybrid Model of concept analysis: (1) the theoretical phase; (2) the fieldwork phase and (3) the analytical phase. Hybrid concept analysis method was chosen because its inclusion of married women's perspectives enriches the limits of sexual health search literature. RESULT: The critical attributes of sexual satisfaction were investigated. They included 'two-dimensional structure', 'an affective response', 'a means to achieve marital satisfaction', 'unique', 'a concept based on expectations' and 'a concept on shadow of values'. CONCLUSION: The concept analysis of sexual satisfaction showed some of the attributes and antecedents for this concept that, have not been mentioned in the literature. PMID- 26153167 TI - Seroclearance of Hbsag in Chronic Hepatitis B Virus Patients on Lamivudine Therapy: A 10 Year Experience. AB - INTRODUCTION: The aim of this study was to determine hepatitis B surface antigen (HBsAg) seroclearance rate among patients treated with lamivudine at a specialized tertiary care referral hospital in Tehran, Iran. METHODS: All patients on lamivudine (biovudin(r)) therapy at a dose of 100 mg/day, who showed seroclearnace between March 2001 and September 2011 were recruited. The main evaluation parameters were duration of HBsAg seroclearance and duration of HBsAg seroconversion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using standard methods. HBsAg seroclearance was defined as two consecutive negative serums HBsAg at least 6 months apart, whereas HBsAg seroconversion was defined as the disappearance of serum HBsAg and the presence of anti-HBs for >6 months. RESULTS: A total of 203 chronic HBV patients treated with lamivudine at a dose of 100 mg/day were included in the study. HBsAg seroclearance and seroconversion were observed in 11 patients after the initiation of the lamivudine therapy. Overall, in lamivudine responder patients, the mean time to HBsAg seroclearance was 26.90+/-10.93 months (range: 12-48 months). Furthermore, the responders showed seroconversion after a mean time of 26.90+/-11.08 months from the initiation of lamivudine therapy. When comparing the characteristics of those who have responded to lamivudine and those who have not responded, baseline HBV-DNA levels was significantly lower in responder than non responder patients (p<0.001). Meantime, there was no difference in age, sex, baseline ALT, AST and liver biopsy score between lamivudine responder and lamivudine non-responder patients. CONCLUSION: Despite introduction of tenofovir and entecavir as first line treatment for chronic HBV infection, lamivudine remains to be a low cost, safe and effective drug for HBsAg seroclearnace. PMID- 26153168 TI - The Comparison of vaginal cream of mixing yogurt, honey and clotrimazole on symptoms of vaginal candidiasis. AB - BACKGROUND: Vulvovaginal candidiasis is known as one of the most common fungal infection among women of reproductive age and considered as an important public health problem. In recent years, due to resistance to common antifungal medication, the use of traditional medicine of anti-fungal and herbal treatment increased. Therefore the objective of this study was to determine the effects of vaginal cream, mixture of yogurt and honey and comparing it with clotrimazole vaginal cream on symptoms of Vulvovaginal candidiasis in patients. METHODS: In this randomized, triple blind clinical trial of 70 non-pregnant women infected with Candidal vulvovaginitis were placed in two groups of Vaginal cream mixed of yogurt and honey recipients (N=35) and clotrimazole vaginal cream (N=35). Both groups were treated for 7 days. At the beginning of study, Clinical and laboratory signs and symptoms were registered 7 and 14 days after treatment by questionnaire, observation form and secretions culture results. Data by chi square test, t test, McNemar tests were analyzed by SPSS version 21. Significance level of 0.05 was considered. RESULTS: The result of present study reveals the significant differences in symptom improvement of ' yogurt and honey, than clotrimazole group (P<0.05) and also Positive results of the first cultures (one week after treatment) in "yogurt and honey" and clotrimazole (20% versus 8.6%) and second time cultivation (14 days after treatment) (17/1% versus 8.6%) were similar and there was no significant differences between the two groups. (P>0.05) CONCLUSION: This study indicated that he therapeutic effects of vaginal cream, yogurt and honey is not only similar with clotrimazole vaginal cream but more effective in relieving some symptoms of vaginal candidiasis. Therefore, the use of this product can be suggested as an herbal remedy for candida infection treatment. PMID- 26153169 TI - Spiritual Journey in Mothers' Lived Experiences of Caring for Children With Autism Spectrum Disorders. AB - INTRODUCTION: Helping mothers who have children with autism spectrum disorders requires understanding of their lived experiences. This study aims to uncover the spiritual journey as a main theme in Iranian mothers' experiences. METHOD: This hermeneutic phenomenological study is a part of a larger study undertaken for partial fulfillment of the requirement for PhD dissertation in nursing. The main study was performed on 18 cases of Iranian mothers, with experience of caring for a child with an autism spectrum during 2011-2012. They were selected based on purposeful sampling method. Semi -structured interviews for data collection were used. Data analyses were done with the interpretative method. RESULTS: Spiritual journey is one of the main themes of the phenomenon under study in the original project. It consists of three sub -themes each of which supported by a number of common meaning. The sub-themes and their common meanings in parenthesis are (1) Descent: wondering between what is and what will be (having sorrowful tale, unanswered question, escaping from reality, losing hope) (2) Connecting to deity: reflection on the failure in her struggle (gratefulness, surrendering to god, having the divine test) (3) Ascent: helping her child is becoming all of the mother's life (to rescue, being hopeful, listening to her inner voice) CONCLUSION: This research concluded that caring for the autistic children led mothers' lives to raise spirituality and enabled them to help their children and themselves, to grow and be refined in this process. PMID- 26153170 TI - Prevalence of Sinus Tract in the Patients Visiting Department of Endodontics, Kermanshah School of Dentistry. AB - INTRODUCTION: Sinus tract is one of the manifestations of chronic dental infections, which is a path for the drainage of the infection and pus. The present study was aimed to investigate the prevalence of sinus tract with dental origin analyze the correlation between sinus tract and related factors. METHODS: This study was conducted on 1527 patients, visiting Kermanshah school of dentistry, in 2014.The related teeth were examined in terms of vitality test and exact location of sinus tract. Moreover, the causes of this lesion and the needs for root canal treatment were assessed in these teeth. Having obtained the data from the patients, analyzed by Mann-Whitney, Chi-square tests. RESULTS: The frequency of sinus tract was 9.89% patients. There was a significant correlation between the prevalence of sinus tract and factors such as age, general health status, location of sinus tract and history of root canal treatment. The prevalence of sinus tract in maxilla was higher than the mandible (p=0.087). The prevalence of sinus tract in the posterior teeth (69.54%) was significantly higher than that of anterior teeth (30.46%) (p=0.000). From 724 teeth with periapical inflammation and radiolucency, 9.89% teeth had odontogenic sinus tract, and 23.42% teeth with history of root canal treatment had sinus tract. CONCLUSIONS: The most common cause of sinus tract incidence was previous root canal treatment. Therefore, clinicians need to pay a more attention to examining the posterior teeth referred for endodontic treatment. PMID- 26153171 TI - Child Weight Growth Chart and Its Associated Factors in Birth Cohort of Maku Using a Growth Curve Model and LMS Method. AB - BACKGROUND: Infant growth is defined as a positive change in body size over a period of time, and is a sensitive predictor of social health. The most effective way to determine child growth is by measuring birth weight and constructing a weight growth trajectory. Many studies were conducted on the effects of different factors on birth weight, but investigations of these effects on growth trajectory are really sparse. This study analyzes longitudinal data to determine factors affecting growth trajectory and used LMS chart for comparing children. MATERIALS AND METHODS: In a cohort study, 256 neonates born in 2004 in Maku, Iran, were recruited and were followed until 2009.The weight of the neonates were measured at 12 occasions from birth, until the age of 5 years. A growth curve model was used to determine the affecting factors. The parametric LMS method was used to construct the reference centiles curve of the weight (5th, 50th, 95th percentiles). FINDINGS: The findings show that while controlling the other factors, birth region, breast feeding duration, mother's education and infants' gender significantly influenced the longitudinal weight rate. However, other variables did not reveal any significant association with growth. The growth charts increased rapidly from birth to 5 years of age for both sexes. It was observed that male children grew faster than females, through the first year of age up to 5 years. CONCLUSION: Although every child has a growth potential, this capacity could be influenced by various factors and can be compared with other infants through a growth chart. We used longitudinal data to obtain the risk factor of growth trajectory. LMS method was also used for description of growth. Thereafter, the weight chart of Shiraz, southern Iran's corresponding infants, was compared. PMID- 26153172 TI - Policies and Programs for Prevention and Control of Diabetes in Iran: A Document Analysis. AB - Trend analysis in 2005 to 2011 showed high growth in diabetes prevalence in Iran. Considering the high prevalence of diabetes in the country and likely to increase its prevalence in the future, the analysis of diabetes-related policies and programs is very important and effective in the prevention and control of diabetes. Therefore, the aim of the study was an analysis of policies and programs related to prevention and control of diabetes in Iran in 2014. This study was a policy analysis using deductive thematic content analysis of key documents. The health policy triangle framework was used in the data analysis. PubMed and ScienceDirect databases were searched to find relevant studies and documents. Also, hand searching was conducted among references of the identified studies. MAXQDA 10 software was used to organize and analyze data. The main reasons to take into consideration diabetes in Iran can be World Health Organization (WHO) report in 1989, and high prevalence of diabetes in the country. The major challenges in implementing the diabetes program include difficulty in referral levels of the program, lack of coordination between the private sector and the public sector and the limitations of reporting system in the specialized levels of the program. Besides strengthening referral system, the government should allocate more funds to the program and more importance to the educational programs for the public. Also, Non-Governmental Organizations (NGOs) and the private sector should involve in the formulation and implementation of the prevention and control programs of diabetes in the future. PMID- 26153173 TI - Safety and Efficacy of Propranolol in Comparison With Combination of Fentanyl and Ketamine as Premedication in Cataract Surgery Under the Topical Anesthesia. AB - This study evaluated the safety and effects of propranolol as a premedication before cataract surgery and compared them with the usual combination doses of fentanyl and ketamine. Among all reffered patients to Feiz Hospital of Esfahan for cataract surgery, 122 patients between Mar to Sep 2010 were enrolled in this study and randomly allocated into one of the following equal groups: 40 mg propranolol, 2 hours before surgery and combination of 15 mg ketamine and 50 ug fentanyl l. 5 min before surgery. The ability to control of hemodynamic instabilities caused by stress and to gain patients satisfaction was compared between two groups. Also, the efficacy of each premedication to control of hemodynamic changes during surgery were evaluated and compared. No significant differences were seen in the patients satisfaction and controlling of stress induced hemodynamic changes between two groups (P>0.05). However, patients in ketamine + fentanyl group showed more nausea and less pain during and after surgery. Moreover, no significant adverse effects were reported during and after the surgery. Our results demonstrated that propranolol can be used safely as a premedication in cataract surgery in the comparable efficacy to ketamine plus fentanyl premedication. PMID- 26153174 TI - The Effect of Mother's Voice on Arterial Blood Sampling Induced Pain in Neonates Hospitalized in Neonate Intensive Care Unit. AB - BACKGROUND AND OBJECTIVE: Due to devastating effects of pain in neonates, it is very important to ease it though safe and feasible methods. This study was to determine the effect of familiar auditory stimuli on the arterial blood sampling (ABS) induced pain in term neonates. RESEARCH METHOD: This study was done on 30 newborns hospitalized in neonate intensive care unit (NICU) of a hospital in Tehran. Research samples were selected by using convenience sampling and randomly divided into two groups of control and test. In the test group, the recorded mothers' voices were played for the newborns before and after blood sampling procedure. Then, pain measures were recorded 10 minutes before, during and 10 minutes after blood collection based on Neonatal Infant Pain Scale (NIPS); then the pain level changes were reviewed and studied. FINDINGS: The findings showed significant differences between the control and test groups that indicating the effect of mother's voice on reducing the pain of neonates during the ABS (p<0.005). CONCLUSION: Research findings demonstrate that mother's voice reduces ABS induced pain in the term neonates. PMID- 26153175 TI - Reconsidering Planning and Management of Medical Devices Procurement in Public Health Services in Cyprus. AB - Hospital procurement is a crucial field for any health care system, not only for economic reasons but also for reasons related to the quality and safety of the services provided. That is why the process of procurement is, in most countries, governed by a strict legal framework and policy mechanisms. This study investigates the problems and inefficiencies associated with the procurement of medical devices in public hospitals in Cyprus and formulates empirically documented proposals for improvement. Using the Delphi method, a group of 38 experts approach the procurement system in Cyprus from different angles, achieving high rates of consensus on 35 different statements on the weaknesses and problems of the current medical device procurement system, as well as presenting proposals and recommendations for improvement. The findings are highly valuable for future policy initiatives in Cyprus in the light of the economic crisis and the expected implementation of the new General Health Insurance System (GeSY), which the Government of the Republic of Cyprus and the Troika has agreed. PMID- 26153176 TI - Preparedness of County Referral Health Facilities in Implementing Adolescent Friendly Health Services: A Case Study of Mama Lucy Kibaki Hospital. AB - Health service delivery is a key pillar of the health system management. The World Health Organization recently emphasized the need to develop adolescent friendly health services to improve the care provided to young people throughout the world. However, there is limited peer reviewed literature on this subject therefore necessitating assessment of whether the existing health facilities are prepared to implement the adolescent friendly health services. Adolescent friendly health services remains a relatively new and sensitive area mainly due to restrictive norms and policies guiding the services. After International Conference on Population and Development in 1994, countries started implementing adolescent friendly health services. The Government of Kenya together with partners in an attempt to address the health challenges came up with the Adolescent package of care (APOC) in 2013 whose guidelines were finalized in November 2014 and released for use by service providers . Despite this package of care, there is still ineffective staff capacity in relation to skills and knowledge gap of health professionals, training needs, health resources as well as health system factors that can affect implementation of AFHS. The study explored ways of mitigating or addressing the barriers to implementation of these services. The study used both quantitative and qualitative approaches to collect data. The study utilized survey research adapting descriptive cross sectional design and semi-structured questionnaire to interview 348 health care providers and 472 adolescents in Mam Lucy Kibaki Hospital from 3rd May 2014 to 16 June 2014. The key informants were mainly nurses, clinical officers and Medical doctors who were working at the health service delivery area at the time of study and were interviewed using an interview guide. The managers at the hospital were interviewed using an in-depth interview guide while the adolescents were interviewed through interview guide and focused group discussion. Quantitative data was analyzed using Statistical Package for Social Sciences (SPSS) Version 18.0. Descriptive statistics and chi-square tests were performed to determine significant associations. The study established that sex, age, level of education and adolescent awareness about existence of friendly health services offered were significantly associated with utilization at p<0.05. Long queues, unfavorable working hours and lack of money negatively affected consumption of AFHS. The study concluded that the utilization of health services among the adolescents was low largely due to unfriendliness of the health care providers at health facilities and lack of awareness of AFHS services. In view of the findings, this study recommends need for the Government through the Ministry of Health and partners in health service provision to increase the number of AFHS and ensure that the recommendations of Adolescent Package of care is implemented fully with good evaluation strategies in place. Laborious awareness drives to sensitize the adolescents about the available services through rigorous health education and increased involvement of both parents/guardians and teachers to scale up implementation are also recommended. PMID- 26153177 TI - Improvement in Knowledge Level of Associate Degree Nursing Students in Zarqa University College Regarding Care for Patients With Indwelling Urinary Catheters After Joining an Educational Session. AB - BACKGROUND: Care for patients with indwelling urinary catheter is one of the most important factors in preventing problems associated with indwelling urinary catheters. Caregiver education about caring of indwelling urinary catheters is important the same as patient education to prevent urinary catheters problems. METHODS: A pre test post test control group design was used with nursing students of Zarqa University College. Data were collected through self-administered questionnaire. RESULTS: Experimental group did not do better in the posttest than the control group after they joined an educational session about caring for patients with indwelling urinary catheter. Level of student (first year vs. second year) has been identified as a covariate that may have distorted the results. CONCLUSION: One educational session is insufficient to change level of knowledge regarding caring for patients with indwelling urinary catheter, in addition to considering the level of nursing student when conducting the educational session. PMID- 26153178 TI - Multilevel Causal Analysis of Socio-Psychological and Behavioral Factors of Health Providers and Clients That Affect Health Behavioral Modification in Obesity. AB - The Comprehensive Lifestyle Intervention, which integrates behavioral therapy, is the main ideal management of the clients with obesity. Various socio psychological factors can affect outcome of the program. THE PURPOSES: to determine the socio-psychological factors at the client and provider groups that affect health behavior modification (HBM) in obese clients, and to investigate the cross-level interaction of factors that affect HBM. The samples included 87 health providers and 412 clients using stratified random sampling. Hierarchical Linear Model was used to analyze in a questionnaire with reliability of 0.8-0.9. RESULTS: 1) for the clients: 1.1) Attitudes towards healthy behavior (AHB), health-related knowledge, and trust in the provider predicted self-efficacy at 49.40%; 1.2) AHB and support from the provider predicted self-regulation at 75.50%; and 1.3) AHB, trust in the provider and support from the provider predicted self-care at 26.6%. 2) for the health providers: 2.1) Health quotient (HQ), project management (PM), support from the team, and the team emotional quotient (EQ) predicted self-efficacy at 71.30%; 2.2) PM and HQ predicted self regulation at 51.60%; and 2.3) PM, team EQ and HQ predicted self-care at 77.30%., 3) No cross-level interaction of factors between the clients and the providers was identified to affect HBM. CONCLUSION: the obese client's AHB is the factor that significantly influenced self-efficacy, self-regulation and self-care (3SELF). At the health provider level, both HQ and PM significantly influenced 3SELF. Behavioral. PMID- 26153179 TI - Knowledge, Attitude and Practice of Nurses Regarding Organ Donation. AB - INTRODUCTION: Treatment team charged to help patients and their family making decision about donate organs in the final stage of life. Hence, their knowledge and attitude is important to plan of increasing the rate of organ donation. MATERIALS AND METHODS: About 150 nurses recruited in this cross-sectional study randomly. After taking informed consent, questionnaires were filled. The data collection tool was a multipart questionnaire including demographic information, 18 questions about attitude and practice and 15 question about knowledge toward organ donation. Data were analyzed by SPSS software using K-squire, Pearson correlation test, T-test, variance analyze on 95% confidence interval. RESULTS: Most of participants (76%) were 25-44 years old. About 81.3% of them were female (n=122). The attitude average score between males and females was 85.25+/-35.61 and 70.37+/-46.53, respectively. The practice average score in females was 34.43+/-47.71 and between males was 29.63+/-46.53. The knowledge average scores were 50.60+/-16.19 and 56.54+/-17.48 for two groups (p>0.05). The knowledge average scores between different age groups was significant (p<0.05). There was a direct and significant relation between attitude and practice (r=+0.33, p<0.05), attitude and Factors influencing attitude and practice (r=0.866, p<0.05), but the relation between attitude and knowledge was indirect and significant (r=-0.183, p<0.05). CONCLUSIONS: Since the medical team are most important adviser for promote activities related to organ donation, it seems that educational curriculum and facilities should applied to enhance attitude and behavior favorable change of personnel towards this issue. PMID- 26153180 TI - Interaction of Physical Exposures and Occupational Factors on Sickness Absence in Automotive Industry Workers. AB - INTRODUCTION: Increased sickness absence in recent years has been a trouble making issue in industrial society. Identify the causes of sickness absence and its influencing factors, is an important step to control and reduce its associated complications and costs. The aim of this study was to evaluate main factors associated with the incidence of sickness absence. PROCEDURE: In 2012, a cross-sectional study on 758 employees of a car accessories producing company was applied and relevant information about the number of days and episodes of sickness absence, Disease resulting in absence from work, personal features, occupational factors and physical exposures were collected. To determine risk factors associated with sickness absence, Logistic regression analysis was used. RESULTS: The most common diseases leading to sickness absence in order of frequency were Respiratory diseases, musculoskeletal disorders, gastrointestinal diseases and injuries at work. Musculoskeletal disorders increased the danger of long term absence by 4/33 times. Blue collar and shift works were the most important occupational factors associated with the incidence of sickness absence. The main physical factors that affect incidence of sickness absence were frequent bending-twisting and heavy lifting. CONCLUSION: Identifying controllable factors of sickness absence and trying to prevent and modify them such as compliance of ergonomic principals to decrease physical can be effective in reducing sickness absence. PMID- 26153181 TI - Main Determinants of Supplementary Health Insurance Demand: (Case of Iran). AB - INTRODUCTION: In the majority of developing countries, the volume of medical insurance services, provided by social insurance organizations is inadequate. Thus, supplementary medical insurance is proposed as a means to address inadequacy of medical insurance. Accordingly, in this article, we attempted to provide the context for expansion of this important branch of insurance through identification of essential factors affecting demand for supplementary medical insurance. METHOD: In this study, two methods were used to identify essential factors affecting choice of supplementary medical insurance including Classification and Regression Trees (CART) and Bayesian logit. To this end, Excel(r) software was used to refine data and R(r) software for estimation. The present study was conducted during 2012, covering all provinces in Iran. Sample size included 18,541 urban households, selected by Statistical Center of Iran using 3-stage cluster sampling approach. In this study, all data required were collected from the Statistical Center of Iran. RESULTS: In 2012, an overall 8.04% of the Iranian population benefited from supplementary medical insurance. Demand for supplementary insurance is a concave function of age of the household head, and peaks in middle-age when savings and income are highest. The present study results showed greater likelihood of demand for supplementary medical insurance in households with better economic status, higher educated heads, female heads, and smaller households with greater expected medical expenses, and household income is the most important factor affecting demand for supplementary medical insurance. CONCLUSION: Since demand for supplementary medical insurance is hugely influenced by households' economic status, policy-makers in the health sector should devise measures to improve households' economic or financial access to supplementary insurance services, by identifying households in the lower economic deciles, and increasing their financial ability to pay. Moreover, insurance companies should adjust their insurance policy according to clients' needs, household characteristics, and their incomes. PMID- 26153182 TI - Health Information Economy: Literature Review. AB - INTRODUCTION: Health Information Economy (HIE) is one of the broader, more complex, and challenging and yet important topics in the field of health science that requires the identification of its dimensions for planning and policy making. The aim of this study was to determine HIE concept dimensions. METHODS: This paper presents a systematic methodology for analyzing the trends of HIE. For this purpose, the main keywords of this area were identified and searched in the databases and from among 4775 retrieved sources, 12 sources were studied in the field of HIE. RESULTS: Information Economy (IE) in the world has passed behind four paradigms that involve the information evaluation perspective, the information technology perspective, the asymmetric information perspective and information value perspective. In this research, the fourth perspective in the HIE was analyzed. The main findings of this research were categorized in three major groups, including the flow of information process in the field of health (production. collection, processing and dissemination), and information applications in the same field (education, research, health industry, policy, legislation, and decision-making) and the underlying fields. CONCLUSION: According to the findings, HIE has already developed a theoretical and conceptual gap that due to its importance in the next decade would be one of the research approaches to health science. PMID- 26153183 TI - Lived Experiences of Iranian Novice Nursing Faculty in Their Professional Roles. AB - Many studies have focused on understanding the novice nursing faculty experiences on their roles and challenges that they encounter. But there are merely little evidences about Iranian novice nursing faculty experiences to perform their roles. In many universities of Iran, a novice faculty has to attend in a set of educational workshops (e.g. teaching and assessment methods), which are not based on their specific needs. Qualitative approach may provide first hand data needed to understand novice nursing faculty perceptions to develop an actual empowerment program. A qualitative design based on phenomenological approach was applied to uncover the meaning of novice nursing faculties' lived experiences in Mashhad University of Medical Sciences (Iran). Five main themes emerged from data as: "Importance of support", "Bewilderment", "Efficiency concern", "Concern of being accepted" and "Clinical education: Walking on the edge". These themes implied to uncertainty about fulfilling the academia expectations by novice faculty, desire to overcome the challenges, time limitation, and, unfriendly behavior from senior colleagues. Findings support that more than formal programs, such as workshops, the novice faculty can be empowered by other approaches (e.g. mentorship programs) where they can safely transit into academia under supervision of experienced colleagues. Also, this may facilitate the socialization process of novice faculty to academia and clinical fields. PMID- 26153184 TI - A Study of Comparative Advantage and Intra-Industry Trade in the Pharmaceutical Industry of Iran. AB - BACKGROUND: Drug costs in Iran accounts for about 30% of the total health care expenditure. Moreover, pharmaceutical business lies among the world's greatest businesses. The aim of this study was to analyze Iran's comparative advantage and intra-industry trade in pharmaceuticals so that suitable policies can be developed and implemented in order to boost Iran's trade in this field. METHODS: To identify Iran's comparative advantage in pharmaceuticals, trade specialization, export propensity, import penetration and Balassa and Vollrath indexes were calculated and the results were compared with other pharmaceutical exporting countries. The extent and growth of Iran's intra-industry trade in pharmaceuticals were measured and evaluated using the Grubel-Lloyd and Menon Dixon indexes. The required data was obtained from Iran's Customs Administration, Iran's pharmaceutical Statistics, World Bank and International Trade Center. RESULTS: The results showed that among pharmaceutical exporting countries, Iran has a high level of comparative disadvantage in pharmaceutical products because it holds a small share in world's total pharmaceutical exports. Also, the low extent of bilateral intra-industry trade between Iran and its trading partners in pharmaceuticals shows the trading model of Iran's pharmaceutical industry is mostly inter-industry trade rather than intra-industry trade. In addition, the growth of Iran's intra-industry trade in pharmaceuticals is due to its shares of imports from pharmaceutical exporting countries to Iran and exports from Iran to its neighboring countries. CONCLUSIONS: The results of the analysis can play a valuable role in helping pharmaceutical companies and policy makers to boost pharmaceutical trade. PMID- 26153185 TI - Unaccompanied Asylum-Seeking Refugee Children's Forced Repatriation: Social Workers' and Police Officers' Health and Job Characteristics. AB - During the past ten years the number of unaccompanied asylum-seeking refugee children has dramatically increased in Sweden. Some of them are permitted to stay in the receiving country, but some are forced back to their country of origin. Social workers and police officers are involved in these forced repatriations, and such complex situations may cause stressful working conditions. This study aimed to bridge the gap in knowledge of the relationship between general mental health and working with unaccompanied asylum-seeking refugee children who are due for forced repatriation. In addition, the role of psychosocial job characteristics in such relationships was investigated. A questionnaire including sociodemographic characteristics, the Swedish Demand-Control-Support Questionnaire, and the 12-item General Mental Health Questionnaire were distributed nationally. Univariate and multivariable regression models were used. Poorer mental health was associated with working with unaccompanied asylum seeking refugee children among social workers but not among police officers. Psychological job demand was a significant predictor for general mental health among social workers, while psychological job demand, decision latitude, and marital status were predictors among police officers. Findings are discussed with special regard to the context of social work and police professions in Sweden. PMID- 26153186 TI - Examining Factor Structure and Validating the Persian Version of the Pregnancy's Worries and Stress Questionnaire for Pregnant Iranian Women. AB - BACKGROUND AND OBJECTIVES: Pregnant women tend to experience anxiety and stress when faced with the changes to their biology, environment and personal relationships. The identification of these factors and the prevention of their side effects are vital for both mother and fetus. The present study was conducted to validate and to examine the factor structure of the Persian version of the Pregnancy's Worries and Stress Questionnaire. MATERIALS AND METHODS: The 25-item PWSQ was first translated by specialists into Persian. The questionnaire's validity was determined using face, content, criterion and construct validity and reliability of questionnaire was examined using Cronbach's alpha. Confirmatory factor analysis was performed in AMOS and SPSS 21. Participants included healthy Iranian pregnant women (8-39 weeks) who refer to selected hospitals for prenatal care. Hospitals included private, social security and university hospitals and selected through the random cluster sampling method. FINDINGS: The results of validity and reliability assessments of the questionnaire were acceptable. Cronbach's alpha calculated showed a high internal consistency of 0.89. The confirmatory factor analysis using the c2, CMIN/DF, IFI, CFI, NFI and NNFI indexes showed the 6-factor model to be the best fitted model for explaining the data. CONCLUSION: The questionnaire was translated into Persian to examine stress and worry specific to Iranian pregnant women. The psychometric results showed that the questionnaire is suitable for identifying Iranian pregnant women with pregnancy-related stress. PMID- 26153187 TI - The Prevalence and Causes of Primary Infertility in Iran: A Population-Based Study. AB - BACKGROUND: Primary infertility is a health issue among women over the world. The aim of this study was to investigate the prevalence and causes of primary infertility based on a population-based study in an urban area of Iran. MATERIALS AND METHODS: In a cross-sectional study, a total of 1067 married women who participated in the Tehran Lipid and Glucose Study were randomly selected using systematic random sampling. Unmarried women, those with unwilling pregnancy and duration of marriage below one year were excluded from the study. Data was collected by using validated ad-hoc questionnaires. Descriptive and inferential statistics were used for data analysis. RESULTS: The mean (SD) of age and marriage age of the studied women were 40.3 (9.3) and 20.6 (4.49) years, respectively; the overall prevalence of lifetime primary infertility among couples was 17.3% (185/1067). Ovulatory disorder (39.7%) and male factors (29.1%) were the main causes of primary infertility. In addition, 31 (17%) of the women were diagnosed with more than one cause. According to the logistic regression analysis, primary infertility was independently related to the old age of women (OR: 1.37; 95% CI: 1.14-13.63, P.value: 0.001), higher BMI (OR: 1.95; 95% CI: 1.87-4.14, P.value: 0.003), active smoking (OR: 1.47; 95% CI: 1.38-3.53, P.value: 0.012) and higher educational level (OR: 2.23; 95% CI: 1.12-5.53, P.value: 0.03). CONCLUSION: The prevalence of primary infertility in Iran was higher than the worldwide trends of infertility, indicating that understanding such risks help healthcare providers and policy makers to design and implement interventions to slow down this trend. PMID- 26153188 TI - Culture and Real-Time PCR Based Maternal Screening and Antibiotic Susceptibility for Group B Streptococcus: An Iranian Experience. AB - INTRODUCTION: Vertical Transmission of group B streptococcus (GBS) from a vagina colonized mother to her infant upon rupture of membranes (ROM) or after the onset of labor can cause life-threatening infections in newborn. Although intrapartum antibiotic prophylaxis (IAP) can significantly decrease neonatal GBS diseases, this issue has potentiated the emergence of antibiotic resistance strains. Our study examined the colonization rate of GBS using real-time PCR and culture methods, and trends in antibiotic resistance of GBS isolates obtained from pregnant women in Khorramabad, Iran. METHODS: In this cross-sectional study, two vaginal-rectal swabs were collected and analyzed separately from 100 pregnant women at 35-37 weeks of gestation by convenience sampling method. The specimens were subjected to GBS detection using real-time PCR assay and standard culture. Susceptibility pattern of the GBS isolates was examined using the disk diffusion method. RESULTS: GBS carriage rate was 17% and 19% using culture and real-time PCR, respectively. In six samples, the culture was positive and the real-time PCR was negative. Sensitivity and specificity for real-time PCR were 72.7% and 96.1%, respectively using culture as the gold standard. Amongst twenty-two isolates examined, 100% resistance to erythromycin and clindamycin was observed. One isolate (4%) exhibited resistance to penicillin. CONCLUSION: Considering the relatively high GBS carriage rate in Khorramabad, routine antepartum screening for GBS is recommended. Penicillin can remain the antibiotic of choice for IAP; however, in penicillin-allergic mothers, vancomycin can be an alternative antibiotic. PMID- 26153189 TI - Factors Affecting Health Care Utilization in Tehran. AB - INTRODUCTION: Successful health system planning and management is dependent on well informed decisions, so having complete knowledge about medical services' utilization is essential for resource allocation and health plans. The main goal of this study is identification of factors effecting inpatient and outpatient services utilization in public and private sectors. METHODS: This study encompasses all regions of Tehran in 2011 and uses Urban HEART questionnaires. This population-based survey included 34700 households with 118000 individuals in Tehran. For determining the most important factors affected on health services consumption, logit model was applied. RESULTS: Regarding to the finding, the most important factors affected on utilization were age, income level and deciles, job status, household dimension and insurance coverage. The main point was the negative relationship between health care utilization and education but it had a positive relationship with private health care utilization. Moreover suffering from chronic disease was the most important variable in health care utilization. CONCLUSIONS: According to the mentioned results and the fact that access has effect on health services utilization, policy makers should try to eliminate financial access barriers of households and individuals. This may be done with identification of households with more than 65 or smaller than 5 years old, people in low income deciles or with chronic illness. According to age effect on health services usage and aging population of Iran, results of this study show more importance of attention to aged population needs in future years. PMID- 26153191 TI - Effect of Eye Movement Desensitization and Reprocessing (EMDR) on Depression in Patients With Myocardial Infarction (MI). AB - BACKGROUND: Coronary heart disease is the most important cause of death and inability in all communities. Depressive symptoms are frequent among post myocardial infarction (MI) patients and may cause negative effects on cardiac prognosis. This study was conducted to identify efficacy of EMDR on depression of patients with MI. METHODS: This study is a clinical trial. Sixty patients with MI were selected by simple sampling, and were separated randomly into experimental and control groups. To collect data, demographic questionnaire and Beck Depression Questionnaire were used. In experimental group, EMDR therapy were performed in three sessions alternate days for 45-90 minutes, during four months after their MI. Depression level of patients was measured before, and a week after EMDR therapy. Data were analyzed using paired -t- test, t-test, and Chi square. RESULTS: The mean depression level in experimental group 27.26+/-6.41 before intervention, and it was 11.76+/-3.71 after intervention. Hence, it showed a statistically significant difference (P<0.001). The mean depression level in control group was 24.53+/-5.81 before intervention, and it was 31.66+/-6.09 after intervention, so it showed statistically significant difference (P<0.001). The comparison of mean depression level at post treatment, in both groups showed statistically significant difference (P<0.001). CONCLUSION: EMDR is an effective, useful, efficient, and non-invasive method for treatment and reducing depression in patients with MI. PMID- 26153190 TI - Nurse Level of Education, Quality of Care and Patient Safety in the Medical and Surgical Wards in Malaysian Private Hospitals: A Cross-sectional Study. AB - BACKGROUND AND OBJECTIVE: Nursing knowledge and skills are required to sustain quality of care and patient safety. The numbers of nurses with Bachelor degrees in Malaysia are very limited. This study aims to predict the impact of nurse level of education on quality of care and patient safety in the medical and surgical wards in Malaysian private hospitals. METHODOLOGY: A cross-sectional survey by questionnaire was conducted. A total 652 nurses working in the medical and surgical wards in 12 private hospitals were participated in the study. Multistage stratified simple random sampling performed to invite nurses working in small size (less than 100 beds), medium size (100-199 beds) and large size (over than 200) hospitals to participate in the study. This allowed nurses from all shifts to participate in this study. RESULTS: Nurses with higher education were not significantly associated with both quality of care and patient safety. However, a total 355 (60.9%) of respondents participated in this study were working in teaching hospitals. Teaching hospitals offer training for all newly appointed staff. They also provide general orientation programs and training to outline the policies, procedures of the nurses' roles and responsibilities. This made the variances between the Bachelor and Diploma nurses not significantly associated with the outcomes of care. CONCLUSIONS: Nursing educational level was not associated with the outcomes of care in Malaysian private hospitals. However, training programs and the general nursing orientation programs for nurses in Malaysia can help to upgrade the Diploma-level nurses. Training programs can increase their self confidence, knowledge, critical thinking ability and improve their interpersonal skills. So, it can be concluded that better education and training for a medical and surgical wards' nurses is required for satisfying client expectations and sustaining the outcomes of patient care. PMID- 26153192 TI - The Evaluation of Olfactory Function in Patients With Schizophrenia. AB - The aim of this study was to compare olfactory threshold, smell identification, intensity and pleasantness ratings between patients with schizophrenia and healthy controls, and (2) to evaluate correlations between ratings of olfactory probes and illness characteristics. Thirty one patients with schizophrenia and 31 control subjects were assessed with the olfactory n-butanol threshold test, the Iran smell identification test (Ir-SIT), and the suprathreshold amyl acetate odor intensity and odor pleasantness rating test. All olfactory tasks were performed unirhinally. Patients with schizophrenia showed disrupted olfaction in all four measures. Longer duration of schizophrenia was associated with a larger impairment of olfactory threshold or microsmic range on the Ir-SIT (P=0.04, P=0.05, respectively). In patients with schizophrenia, female subjects' ratings of pleasantness followed the same trend as control subjects, whereas male patients' ratings showed an opposite trend. Patients exhibiting high positive score on the positive and negative syndrome scale (PANSS) performed better on the olfactory threshold test (r=0.37, P=0.04). The higher odor pleasantness ratings of patients were associated with presence of positive symptoms. The results suggest that both male and female patients with schizophrenia had difficulties on the olfactory threshold and smell identification tests, but appraisal of odor pleasantness was more disrupted in male patients. PMID- 26153193 TI - Nutritional status and survival among old adults: an 11-year population-based longitudinal study. AB - BACKGROUND/OBJECTIVES: The impact of nutritional status on survival among community-dwelling older adults is unclear. We aimed to investigate the prevalence and association of poor nutritional status, including malnutrition and risk for malnutrition defined by the Mini-Nutritional Assessment-Short Form (MNA SF) with survival, and to explore the role of relevant biomarkers (hemoglobin, albumin and C-reactive protein) in this association. SUBJECTS/METHODS: This study included 3041 participants aged ? 60 in the Swedish National study on Aging and Care-Kungsholmen. On the basis of the total score in MNA-SF, nutritional status for each participant was assessed as normal (score 12-14), risk for malnutrition (8-11) or malnutrition (<8). Over an 11-year follow-up, survival status was observed. Data were analysed using logistic regression, flexible parametric survival and Laplace models. RESULTS: Of all the participants, 51 (1.7%) had malnutrition and 751 (24.7%) were at risk for malnutrition. The multi-adjusted hazard ratio (95% confidence interval) of mortality was 2.40 (1.56-3.67; P<0.001) for malnutrition and 1.49 (1.29-1.71; P<0.001) for risk for malnutrition. The median ages at death of participants with malnutrition and risk for malnutrition were ~3 and 1.5 years shorter than those with normal nutritional status, respectively, whereas malnutrition or risk for malnutrition together with abnormal biomarker (hemoglobin and albumin) levels was related to 1 year more shortened survival. CONCLUSIONS: Malnutrition and risk for malnutrition are highly prevalent and significantly associated with a shorter survival. Poor nutritional status in combination with abnormalities in the biomarkers is associated with even more shortened survival. PMID- 26153194 TI - Pilot study of intravenous melphalan combined with continuous infusion L-S,R buthionine sulfoximine for children with recurrent neuroblastoma. AB - PURPOSE: To evaluate BSO-mediated glutathione (GSH) depletion in combination with L-PAM for children with recurrent or refractory high-risk neuroblastoma (NB) as a means to enhance alkylator sensitivity. PROCEDURE: This pilot study (NCI #T95 0092) administered L-S,R-buthionine sulfoximine (BSO) as a bolus followed by 72 hr continuous infusion of either 0.75 g/m(2)/hr (level 1) or 1.0 g/m(2)/hr (level 2) and melphalan (L-PAM) (15 mg/m(2) bolus at hour 48 of BSO infusion). GSH in blood mononuclear cells and bone marrow was measured by enzymatic assay, BSO in plasma by HPLC. RESULTS: Thirty two patients received 58 courses of therapy (median 1, range 1-4 courses). Blood mononuclear cell GSH decreased (48 hr) to 47% +/- 15.7%. Level 2 mean steady-state concentration (Css) for BSO = 524 +/- 207 MUM and peak L-PAM concentration = 3.32 +/- 1.2 MUM. Grade 3-4 leukopenia and thrombocytopenia were common. There were two deaths from CNS toxicity and acute tubular necrosis; one had a large, intracranial mass, both were receiving cephalosporin antibiotics. No other significant toxicities were seen. There were six responses (five partial and, one mixed) representing an 18% response rate; four/six responses occurred in patients that relapsed following myeloablative therapy and included a 98% reduction in volume (cm(3)) of a pelvic mass, and three/five patients with >3 log reduction of tumor in marrow as measured by immunocytology (sensitivity 1/10(5)). CONCLUSIONS: BSO/L-PAM has activity against recurrent high-risk NB. Exclusion of cephalosporin antibiotics in future clinical trials of BSO may diminish the potential for serious renal and CNS toxicity. PMID- 26153195 TI - Rapidly fluctuating anosmia: A clinical sign for unilateral smell impairment. AB - Reports about fluctuating olfactory deficits are rare, as are reports of unilateral olfactory loss. We present a case of unilateral anosmia with contralateral normosmia, presenting as rapidly fluctuating anosmia. The olfactory fluctuation occurred in sync with the average nasal cycle duration. Examination after nasal decongestion, formal smell testing, and imaging revealed unilateral, left-sided anosmia of sinonasal cause, with right-sided normosmia. We hypothesize that the nasal cycle induced transient anosmia when blocking the normosmic side. Fluctuating olfactory deficits might hide a unilateral olfactory loss and require additional unilateral testing and thorough workup. PMID- 26153196 TI - In vitro study of endogenous CEST agents at 3 T and 7 T. AB - Chemical exchange saturation transfer (CEST) has been an intensive research area in MRI, providing contrast mechanisms for the amplified detection and monitoring of biomarkers and physiologically active molecules. In biological tissues and organs, many endogenous CEST agents coexist, and their CEST effects may overlap. The interpretation of such overlapped CEST effects can be addressed when the individual CEST effects originating from various metabolites are characterized. In this work, we present the in vitro measurements of the CEST effects from endogenous CEST agents that are commonly found in biological tissues and organs, at the external magnetic fields of 3 T and 7 T and under various pH conditions. Together with the proton NMR spectra measured at 11.7 T, these CEST effects have been evaluated in consideration of the chemical exchange rates, chemical shifts, and acidities of the labile protons. Amine protons of small metabolites might not be visible at 3 T, but some of them can be probed at 7 T, wherein their CEST effects may overlap with those from coexisting amide and hydroxyl protons. PMID- 26153197 TI - Effects of Synbiotics on Inflammatory Markers in Patients With Type 2 Diabetes Mellitus. AB - INTRODUCTION: With regard to the relationship between inflammation and insulin resistance and due to the lack of researches conducted about the effect of synbiotics on inflammatory markers in diabetes patients, this study was designed to investigate the effect of these markers. METHODS: A double-blind, placebo controlled trial was conducted among 44 type 2 diabetes patients. They were randomized to symbiotic or placebo group. Patients in the symbiotic group received one symbiotic tablet daily for 8 weeks whereas the placebo group received 1 placebo tablet. The hs-CRP concentration, TNF-alpha and IL-6 were measured by using ELISA kits. The dietary intakes of patients were assessed at the first and the end of the study and analyzed by Nutritionist IV. Data were analyzed by using SPSS 16.0 via paired and independent t-test. RESULTS: Anthropometric and dietary data were not significantly different between the two groups at the first and the end of the study. The serum concentrations of hs-CRP, IL-6 and TNF-alpha decreased significantly in the symbiotic group at the end of week 8 compared to baseline (p<0.05). Also, no significant changes were seen in the placebo group (p>0.05). The reduction in inflammatory markers in the symbiotic group were significant in compared to the placebo group (P<0.05). CONCLUSIONS: Symbiotic supplementation can reduce serum hs-CRP, IL-6 and TNF alpha concentrations, a risk factor for cardiovascular diseases. PMID- 26153198 TI - Influence of Comprehensive Life Style Intervention in Patients of CHD. AB - BACKGROUND & OBJECTIVE: Over the past 30 years, the CHD rates have doubled in India whereas CHD rates have declined by 15% in most developed countries due to lifestyle interventions during the same period. So, the present study was conducted to find out the effectiveness of lifestyle intervention in reducing major risk factors in CHD patients in an Indian setting. METHODS: We conducted this randomized controlled trial on 640 eligible subjects who were randomly assigned to two groups. The study group was given an interventional package at baseline and at three months, detailing the aspects of a healthy lifestyle in relation to CHD risk factors whereas no intervention was provided for the control group. The study subjects were followed at three and six months and the risk factors were assessed to find out reduction, if any, in the prevalence of the risk factors amongst them. RESULTS: There was a significant reduction in hypertension, tobacco, and lack of physical activity at three and at six months (p<0.03) when compared to the baseline in the study group. However, there was no significant reduction in obesity at three months (p=0.148) while the reduction in obesity was significant at six months (p=0.0005) in the study group as compared to the control group. The lipid profile reduced significantly at six months but there was no statistically significant reduction in diabetes at six months in the study group as compared to the control group (p=0.419). INTERPRETATION & CONCLUSION: Except for diabetes, the lifestyle intervention was successful in increasing physical activity, improving the hypertension control, and decreasing lipid profile disorders, obesity, and tobacco use in the study group. PMID- 26153199 TI - The Effect of Applying Direct Observation of Procedural Skills (DOPS) on Nursing Students' Clinical Skills: A Randomized Clinical Trial. AB - BACKGROUND: Remarkable advances in educational measurement have proved need to the implementation of modern and appropriate methods of clinical evaluation. This study was carried out to compare the effect of applying direct observation procedural skills and routine evaluation method on clinical skills of nursing students. METHODS: This randomized clinical trial was conducted on students of Nursing Army College, Tehran, Iran. After obtaining approval from the Ethics Committee of the Baqiyatallah University of Medical Sciences Research Deputy, all nursing students and instructors who agreed to participate in this study sign the informed consent. The participants were randomly assigned into intervention and control groups. After the teachers were trained and an inter-raters reliability test was conducted, evaluation was performed through DOPS in the intervention group while the control groups were evaluated through the routine method. Assessment checklists for two procedures (Intra venous catheterization and change dressing) were valid and reliable. Finally data were analyzed through descriptive and analytical statistics (Chi-square, t-test, Repeated Measure ANOVA) using SPSS version 16. RESULTS: No significant difference was observed between the two groups in terms of demographic variables (P>0.05), but a significant difference was observed between intervention and control scores (P=0.000). In other words, application of DOPS has improved clinical skills of the students significantly. CONCLUSION: Using this new method improved the students' scores in clinical procedures implementation; therefore, we suggest that nursing colleges apply this evaluation method for clinical education. PMID- 26153200 TI - Analyzing the Dimensions of the Quality of Life in Hepatitis B Patientsusing Confirmatory Factor Analysis. AB - BACKGROUND & OBJECTIVES: The scope of the quality of life assessment is not widespread in any time like today. Economists, social scientists and politicians look at this topic from the particular approach. The life quality in hepatitis B patients regarding the degree of its progress is considered a major concern in these patients. Thus, the aim of the study was analyzing the dimensions of the life quality of a group of people suffering from hepatitis B in Mazandaran province in 2012. METHODS: This study was done by descriptive, cross-sectional method on 210 (118 women and 92 men) hepatitis B patients that six month have passed from their diagnosis and formation of follow-up form in health centers, using access sampling method at six regions of Mazandaran province.The instruments of the study were the questionnaire of World Health Organization questionnaire (WHOQOL-BREF) and the chronic liver disease questionnaire (CLDQ). For analyzing the data from descriptive statistics and Kolmogrov-Smirnov test, one sample t-test, two stage Confirmatory factor analysis, Spss and Lisrel software has been used. RESULTS: Findings showed that the social relationship dimension with factor loading of 0.81 has the most amount of coefficient of effectiveness; physical health with factor loading of 0.72, mental health with factor loading of 0.63 and environmental health with factor loading of 0.55 have the least amount of coefficient of effectiveness in creating the general life quality of hepatitis B patients. In the quality of life in hepatitis patients, the emotional function with factor loading of 0.76 has the most coefficient of effectiveness, activity dimension with factor loading of 0.67, fatigue with factor loading of 0.47, abdominal syptoms with factor loading of 0.42 and worry with factor loading of 0.32 have the least coeficient of effectivness in making CLDQ domains of hepatit B patients. CONCLUSIONS: The general quality of life in patients had been below average and social relationship and emotional function must be properly investigated and managed in hepatitis B patients in order to improve life quality. WHOQOL-BREF and CLQD proved to be a useful instrument to assess general life quality in patients and can be helpful to find practical strategies to improving life quality in these patients. PMID- 26153201 TI - Effects of Pistacia Atlantica Extract on Erythrocyte Membrane Rigidity, Oxidative Stress, and Hepatotoxicity Induced by CCl4 in Rats. AB - BACKGROUND: Previous findings have suggested that antioxidants may reduce the levels of free radicals, which induce oxidative damage and play a key role in various diseases. Thus, we evaluated the protective activity of a Pistacia atlantica extract on erythrocyte membrane rigidity, oxidative stress, and hepatotoxicity induced by carbon tetrachloride (CCl4) in rats. MATERIALS & METHODS: Fresh leaves of P.atlantica were collected from the mountains in Yasuj, Iran. Acute oral toxicity (LD50) was evaluated in Wistar rats (200-230 g). Animals were randomly divided into 4 groups, out of which the negative and plant control groups received distilled water and P. atlantica extracts (500 mg/kg), respectively. The toxic rat group received CCl4, while the treatment group received CCl4+P. atlantica extract. Blood plasma was utilized for the estimation of enzyme markers and lipid peroxidation, whereas hemolysate was applied for the determination of superoxide dismutase (SOD) and catalase activities. The levels of cholesterol and phospholipids in erythrocyte membranes were also determined. Rats were killed under anesthesia by cervical dislocation; liver was isolated from each rat and tissues homogenization was prepared for biochemical parameters such as malondialdehyde (MDA) and reduced glutathione (GSH) levels. RESULTS: LD50 values were determined for doses>3000 mg/kg (p.o.). The activities of glutamic pyruvate transaminase (GPT), glutamic oxaloacetate transaminase (GOT), alkaline phosphatase (ALP) and GSH in the protected group were significantly (p<0.001) reduced compared with those of toxic rats. In addition, we observed a decrease in the cholesterol level and an increase in red blood cell membrane phospholipids, SOD, and catalase activities (p<0.001) in the protected group, as compared with toxic rats. Administration of Pistacia atlantica extract normalized liver tissue MDA level (p<0.01) when compared to CCl4 treated group. CONCLUSION: The P. atlantica extract was able to normalize the levels of biochemical markers, including liver enzyme markers, first-line defense enzymes, and lipid peroxidation markers. PMID- 26153202 TI - Driving Behaviors in Iran: A Descriptive Study Among Drivers of Mashhad City in 2014. AB - BACKGROUND: Driver-related behaviors are substantial causes for motor vehicle accidents. It has been estimated that about 95% of all accidents are due to driver-related dangerous behaviors and approximately 60% of accidents are directly caused by driving behaviors. The aim of this study was to assess driving behaviors and its possible related factors among drivers in Mashhad city, Iran. METHOD: In a cross-sectional design, a total number of 514 drivers in Mashhad, Iran Surveyed. Manchester driver behavior questionnaire with 50 questions evaluated dangerous driving behaviors in 4 categories "aggressive violations", "ordinary violations", "errors" and "lapses". RESULTS: In this study, the median age of drivers was 31. Besides, 58.2% of men mentioned having a history of driving accident. Our study indicated smoking and alcohol drinking as risk factors of having more accidents. Hookah abuse is a predictor of aggressive violations and errors. CONCLUSION: This is the first study to assess the relation of personal car and its market value with the likelihood of having accidents. Due to major influences of driving fines, cigarette smoking, alcohol consumption and addiction on violations and errors, we recommend pivotal measures to be taken by road safety practitioners regarding driving surveillance. PMID- 26153203 TI - A Trans-Theoretical Approach to Physical Activity Profile in General Population of Mashhad. AB - Regular physical-activity is necessity for a healthy lifestyle. Despite public health efforts, a minority of population are involved in healthy levels of physical-activity. This study provides evidence about exercise patterns and predictors of Mashhad-Iran population according to TTM change stages. In this cross-sectional study, we surveyed a total number of 564 participants from Mashhad in 2014 by using stages of change questionnaire. Analysis showed 23.4% of participants were in pre-contemplation stage, 18 in contemplation, 24.6% in preparation, 8.10% in action, 14.4% in maintenance and 11.5% were in termination phase. Age, gender, BMI, alcohol consumption, sleep duration, having compeer and encouragement were identified as predictors of pre-contemplation stage. Genders, having company and using bicycle for transportation were predictors of termination phase. Tailor interventions based on the predictors to enhance the physical activity among specific subgroups would be of interest. PMID- 26153204 TI - A Study of Patients and Nurses' Perception of the Quality of Pain Management in the Patients Undergoing Surgery in the Departments of Surgery of Rasht Hospitals in 2013. AB - PURPOSE & FIELD: More than one hundred million people around the world undergo a surgery annually. Although, the surgery itself is a treatment method to relieve pain and discomfort, it can be considered as one of the important factors to make a pain too. Perception and diagnosis of the pain is the most important duty of nurses. Effective pain management after surgery facilitates the patient's recovery, decreases the length of hospitalization and increases the patient satisfaction. This study aims to investigate the patients and nurses' perception of the quality of pain management in the patients undergoing an abdominal surgery. MATERIALS & METHODS: The current study is a descriptive research that has been conducted on 204 candidate patients for the abdominal surgery and the nurses who care them in the departments of surgery of Rasht hospitals by using the Simple Random Sampling method. The necessary tools in gathering data for the questionnaire consist of demographic characteristics. Idval,E et al's Questionnaire for evaluation and pain perception, numerical and visual evaluation tools for the patient and nurse satisfaction with pain relief. Statistical analysis has been made through the 16 version of SPSS software by using descriptive statistics, average and standard deviation. FINDINGS: The results show that the level of patient satisfaction with providing necessary care to relieve pain was 29.1% (maximum), 20.8% (minimum) and 78.7% to the confidence, environment and all areas, respectively. For the nurses, this level was 32.4% (maximum), 16.4% (minimum) and 77.1% to the performance, environment and all areas, respectively. The maximum level of patient perception of satisfaction with pain relief was 49.1% and for the nurses, it was 37.7% (good level). CONCLUSIONS: The results indicated that the patients' perception of providing necessary cares to relieve pain and their satisfaction with the pain relief are more than the nurses and in a good level. PMID- 26153205 TI - Clarifying Evidence-Based Medicine in Educational and Therapeutic Experiences of Clinical Faculty Members: A Qualitative Study in Iran. AB - INTRODUCTION: Although evidence-based medicine has been a significant part of recent research efforts to reform the health care system, it requires an assessment of real life community and patient. The present study strives to clarify the concept of evidence-based medicine in educational and therapeutic experiences of clinical faculty members of Kermanshah University of Medical Sciences (2014). MATERIALS & METHODS: It was a qualitative study of phenomenology. The population consists of 12 clinical faculty members of Kermanshah University Medical Sciences. Sampling was carried out using a purposeful method. Sample volume was determined using adequacy of samples' law. Data gathering occurred through semi-structured interviews. Collaizzi pattern was employed for data interpretation concurrent with data gathering. RESULTS: interpreting the data, three main themes were extracted. They include: 1. Unawareness and disuse (unaware of the concept, disuse, referral to colleagues, experiment prescription) 2. Conscious or unconscious use (using journals and scientific websites, aware of the process). 3. Beliefs (belief or disbelief in necessity). CONCLUSION: It sounds essential to change the behavior of clinical faculty members from passive to active with respect to employing evidence-based medicine as well as to alter negative attitudes into positive ones. In so doing, systematic training program aiming at behavior changing is necessary. Also, providing dissent facilities and infrastructures and removing barriers to the use of EBM can be effective. PMID- 26153206 TI - Effect of Blocking of Neuropeptide Y Y2 Receptor on Tumor Angiogenesis and Progression in Normal and Diet-Induced Obese C57BL/6 Mice. AB - BACKGROUND: Obesity is a risk factor for some types of cancers. Angiogenesis is a necessary step in the multistage progression of tumors such as melanoma. Previous studies reported that neuropeptide Y (NPY) regulates angiogenesis by activating the Y2 receptor on endothelial cells. The present study examined the effects of the NPY Y2 receptor antagonist on tumor weight, angiogenesis and serum levels of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGF-R1), and nitric oxide (NO). METHODS: Twenty four male C57BL/6 mice were divided into control and obese groups. The control group was fed a normal diet whereas the obese group was fed a high fat diet. After 16 weeks, 2*10(6) B16F10 melanoma cells were injected subcutaneously into all animals. Half of the control and the obese animals received 1 uM, 100 uL/kg NPY Y2 receptor antagonist (BIIE 0246) intraperitoneally. After two weeks, the animals were sacrificed, and angiogenic factors and tumor weights and angiogenesis were analyzed. RESULTS: Tumor weight in the obese mice was higher than in the control (p<0.05). Treatment with BIIE 0246 reduced tumor weight in the obese animals (p<0.05), without effect on control group (p>0.05). Administration of an NPY Y2 receptor antagonist decreased tumor angiogenesis (evaluated as capillary density/mm2) and serum VEGF concentration in the obese group without altering serum VEGF-R1 and NO concentrations. CONCLUSIONS: Blockade of the NPY Y2 receptor suppressed tumor growth in obese mice by affecting tumor angiogenesis. Thus, it seems that NPY and its Y2 receptor antagonist might be new targets in melanoma tumor therapy. PMID- 26153207 TI - Improvement of the First Training for Baccalaureate Nursing Students--A Mutual Approach. AB - BACKGROUND: Examination of problems and application of strategies appropriate for clinical education and learning, especially nursing clinical principles and skills internship can improve educational process and satisfaction of nursing students. The aim of the current study was to revise the current status of the fundamentals of nursing course and implement an improvement plan (2012-2014). PARTICIPANTS & METHODS: The present study reports the three rounds of a participatory action-research study with a mutual cooperation approach and focus group discussion, with participation of 104 stakeholders. Content analysis approach was used to analyze the data obtained in focus discussion interviews. In addition, evaluation and reflection were done during the operating rounds, with the participation of all members, including students, were involved. This research program was approved by Shahid Beheshti University of Medical Sciences in Tehran-capital of Iran, at the Research Deputy of Nursing and Midwifery School and ethics committee of the university. RESULTS: The findings of qualitative study detected Lack of consistency in planning and implementation of curriculum, inadequate intra/extra-organizational communication management, inadequate student understanding of situation, improper control of restrictors and improper use of facilitators in teaching and in clinical setting, were among major challenges in clinical skills and principles internship process in the context of this study. Educational decision-making authorities of the School developed an operational program within national curriculum framework through cooperation and reflection in clinical skills and principles training program. CONCLUSION: Planning Fundamentals of Nursing training in partnership with all those involved in practice and education, together with students involved can be effective in reducing educational failures, gap between theory and practice, and in students' accountability and satisfaction. PMID- 26153208 TI - Evaluating International Prostate Symptom Score (IPSS) in Accuracy for Predicting Post-Operative Urinary Retention After Elective Cataract Surgery: A Prospective Study. AB - BACKGROUND: Postoperative urinary retention-a common and important complication of surgical procedures, can occur after any form of surgical intervention, in both sexes and all ages regardless of patients' previous history of urinary problems. The importance of post operative urinary tract retention is due to its effect on development of post operative urinary infection, patient anxiety and discomfort, prolongation of hospital stay and increase in hospital costs and morbidity. The International Prostate Symptom Score (IPSS) is an easy method for quantifying and estimating the association between pre-operative bladder-outflow problems and post-operative urinary retention. The aim of present study was to investigate whether the IPSS could predict the likelihood of patients developing urinary retention after elective cataract surgery. METHODS: One hundred and fourteen male patients older than fifty years old, who were candidate for elective cataract surgery, were enrolled in this study. All patients completed an IPSS questionnaire form before operation, and classified into three groups regarding their score (0-7: mild, 8-19: moderate, 20- 35: severe). RESULTS: Totally 8 patients (7%) developed post-operative urinary retention during first 24 hours after operation. Of the 8 urinary retention patients, 2 had moderate symptoms and 6had severe symptoms. There was a significant difference in developing postoperative urinary retention between patients having mild symptoms and patients having severe symptoms (P-value: 0.025). CONCLUSION: It is concluded that while some litterateurs definitely support the idea that IPSS may be useful for predicting post operative urinary retention, there are still some controversies. Considering our results, it seems that IPSS score is not useful in the accurate prediction of those patients who are likely to develop postoperative retention after surgical procedures other than arthroplasty, and more precise studies are need to be conducted about urinary retention occurring postoperatively in different type surgeries, different methods of anesthesia considering age and gender of patients. PMID- 26153209 TI - Frequency Rate of Atelectasis in Patients Following Coronary Artery Bypass Graft and Its Associated Factors at Mazandaran Heart Center in 2013-2014. AB - INTRODUCTION: As the most common postoperative pulmonary complications after cardiac surgery, atelectasis is one of the most important and serious early postoperative complications and one of the most important causes of prolonged hospitalization, increased costs, and mortality rise. Therefore, the present study was aimed at specifying the frequency of atelectasis in patients following coronary artery bypass graft and its associated factors in Mazandaran Heart Center in 2013-2014. MATERIALS: The present investigation was a descriptive cross sectional study in which sequential sampling was used. It was conducted on 375 patients whose coronary artery bypass graft had been performed by the same surgeon and anesthesiologist. For data collection, first the patients' demographic variables and the information of their surgery were retrieved through their profiles, direct observation, patient inquiry, and the collected data were recorded in the data collection forms. Then, atelectasis was measured before the surgery and on the first and second days after it by taking CXR whose results were checked by two radiologists who were not aware of the previous observations. Data were analyzed through t-test, Pearson test, and Chi-square test using SPSS 16.0. RESULTS: The results of the present study indicated that, 123 out of 375 patients (32.8%) were diagnosed with at least one type of tattletales during the first three days after the surgery. The mean age of the patients who were diagnosed with atelectasis was 62.9 and most of them were female. The results also showed that there was a significant relationship between postoperative frequency of atelectasis and the patients' pulmonary diseases and underlying diseases like diabetes and hyperlipidemia, smoking and alcohol use before the surgery, and transfusion of 4 units of packed red blood cells during the surgery (p<0.05). CONCLUSION: Atelectasis is the most common postoperative complication which emerges more in patients with pulmonary and underlying diseases than other patients. PMID- 26153210 TI - Health System's Responsiveness of Inpatients: Hospitals of Iran. AB - INTRODUCTION: Additional to improving health and ensuring equitable financing that are two predominant goals of health system, another important goal of health systems is responsiveness to people's non-medical expectations. In this study we try to assess the health system's responsiveness in academic and non-academic hospitals. METHODS: This is a cross sectional study done in summer 2014 in Mashhad-Iran, we surveyed a total number of 403 inpatients by multi-stage sampling. A questionnaire of responsiveness and a check list included demographic variables and characteristics of hospitalization were completed by trained interviewers. Scales from 0 to 10 was applied for each questionnaire at the end of assessment of questions. RESULT: 403 participants Took part in this survey from 10 hospitals (6 academic and 4 non-academic hospitals). 124(30.8%) were from non-academic and 279(69.2%) from academic hospitals 140(34.7%) of patients were male and 263(65.3%) were female. mean age of participants was 36.77+/-1.52 years. The mean total score of responsiveness was 7.12+/-1.31 in academic hospitals and 6.99+/-1.38 in non-academic hospitals, considered as good performance. There was no significant difference between total scores of these two groups (p=0.38). Health care responsiveness score was higher in private (8.35+/-0.95) than other kinds of hospitals and charity hospitals had the lowest score (5.98+/-0.51). CONCLUSION: Responsiveness of health care system at hospitals is an important parameter for measuring patients' perception of quality of health care. Although responsiveness rate of our hospitals are good but some components such as: choice health care providers, respect to autonomy of individuals, clear communication and confidentiality received lower responsiveness scores, therefore they require more attention and these domains can be the more significant choices that should be considered while designing improvement programs. PMID- 26153211 TI - The Effect of Dust Storm on the Microbial Quality of Ambient Air in Sanandaj: A City Located in the West of Iran. AB - BACKGROUND & AIMS: The presence of pathogenic microorganisms in the dust storm can cause diseases such as Asthma, Pneumonia, and respiratory infections. The aim of this study was to determine the relationship between air-borne particles with airborne microorganisms in normal and dusty days in Sanandaj, a city located in the west of Iran. MATERIALS & METHODS: Air sampling was conducted during the normal and dusty days through Andersen single-stage impactor (28.3 L/min) for 2.5 min. Air particles concentration (PM10) was measured daily and microbial sampling was also conducted on every six days and on the dusty days. Finally, the data was analyzed by SPSS-16 (ANOVA and paired T-tests). RESULTS: The concentration of airborne microorganisms (bacteria and fungi) was increased by an increase of the airborne particles. Particles concentration in May, June and July (twice per month) was more than of the standard value. The predominant species of bacteria and fungi during the occurrence of Dust storm was Bacillus spp. (56.2% of total bacteria) and Mycosporium spp. (28.6% of total fungi), respectively. DISCUSSION AND CONCLUSION: The results showed that the number of airborne microorganisms (bacteria and fungi) increased during the dust storm. Therefore, the microorganisms in the dust storm can cause biological harmful effects on human health. PMID- 26153212 TI - Biodegradation of Phenol in Synthetic Wastewater Using a Fixed Bed Reactor With up Flow Sludge Blanket Filtration (FUSBF). AB - In the present study, the removal of phenol from synthetic wastewater was evaluated in a fixed bed reactor with up flow sludge blanket filtration (FUSBF) in comparison with a typical USBF system. At hydraulic retention time (HRT) of 24 hours and solid retention time (SRT) of 20 day, the effect of initial concentration of phenol (260-1020 mg/L) on phenol and chemical oxygen demand (COD) removal efficiency (%) was investigated in both systems. The effect of the presence of fixed bed was determined throughout the operational period. The results showed that the FUSBF system had a better ability than the typical USBF system in terms of phenol and COD removal. The average phenol and COD removal at phenol concentration of 312 mg/L was 97.52% and 92.82% for the FUSBF system and 92.80% and 82.18% for the typical USBF system, respectively. At HRT of 24 h and organic loading rate (OLR) of 30 g/m(-3).h(-1), the amount of phenol removal was 82.1%. At OLR of 30 g/m(-3).h(-1), role of fixed bed in phenol and COD removal was 25.01% and 29.3%, respectively, overall, the FUSBF system has a higher efficiency and ability than that of typical USBF and can be used for the purification of industrial wastewater containing refractory organic compounds such as phenol. PMID- 26153213 TI - Drug Addiction in Patients With Chronic Schizophrenia and Its Relation With Psychopathology and Impulsiveness. AB - BACKGROUND: Using drugs is a common affliction in patients with Schizophrenia affecting their increasing death rate. They have to tolerate longer treatment time and staying in hospital and they further show more violence and their living quality decreases. It also seems that this factor is among the influential factors of unsuccessful results in treating these patients. OBJECTIVES: Despite all this, there is little data about drug consumption, psychopathology and demographic information in patients with chronic schizophrenia in Iran. This paper reviews the relation between drug consumption and the mentioned qualities in patients afflicted by chronic Schizophrenia. METHODS: In this cross-sectional study, 100 patients with Schizophrenia were interviewed based on DSM-IV-TR diagnostic parameters and according to a psychiatrist's views. The severity of psychopathology was evaluated, using PANSS, (SCID-I) DSM-IV and BARRAT. RESULTS: The results show that in patients with chronic schizophrenia, there is a meaningful relation between cigarette consumption and education, gender, family background and BARRAT. It also has a direct correlation with Attention and Motor. Drug consumption has a meaningful relation with gender and Motor (p<0.05). But it has no relation with BARRAT. Of the variables having a relation with correlation, cigarette and treatment period factors have a predicting effect for drug consumption. CONCLUSIONS: According to the results, drug and cigarette consumption is high among patients with Chronic Schizophrenia. Common cigarette consumption and its relation with impulsiveness increase, and death rate are the reasons which make us take the needed steps to have these patients quit smoking. PMID- 26153214 TI - The Effects of Medicago Sativa and Allium Porrum on Iron Overload in Rats. AB - PURPOSE: Iron overload may occur due to regular blood transfusions and high intestinal iron absorption. Currently, there is no effective drug without side effects for the treatment of iron excess in thalassemia and other iron storage diseases, except chelation therapy, which is the only safe method for iron excretion. Thus, scientists are more focused on medicinal plants rich in phytochemical compounds for the removal of iron in thalassemia. Therefore this study was managed to discover the therapeutic potential of hydro-alcoholic extract of Allium porrum and Medicago sativa for iron chelating potential. METHODS: Aerial parts of Allium porrum and Medicago sativa were collected in Yasuj Iran. Rats were divided into seven groups each containing six. Extracts were administrated in four groups (two groups for each extract) by single doses of each plant with 200 and 400 mg/kg body weight by (i.p.) route every other day for 28 days. Group 1 as negative control received saline (0.5 ml/kg) by (i.p.) route. Positive control received iron dextran 200 mg/kg body weight. Experimental groups 1 and 2 for each plant extract were fed with 200 and 400 mg/kg, hydro alcoholic extract respectively via (i.p.) route, 1 h after the injection of iron dextran. Standard group was treated with deferoxamine (DF) 50 mg/kg by (i.p.) route 1 h after the injection of iron dextran. Serum iron (SI) and serum total iron binding capacity (TIBC) were determined .The serum ferritin was then measured using enzyme immunoassay ELISA kit for rat. For Analysis of data ANOVA test was used. RESULTS: Hydro-alcoholic extract of Medicago sativa and Allium porrum at 400 mg/kg showed significant (p<0.05) iron chelating activity compared to control. The plant extracts with dose 200 mg/kg also reduced the iron and ferritin content but the effect was lower level compared to higher doses. The plant extract effects were similar to that of standard drug deferoxamine. Iron and ferritin levels were significantly reduced in experimental groups when compared to positive group especially in Medicago sativap<0.05. There was no difference between standard drugs and last concentration of plant extracts. CONCLUSION: Protective effect of M. sativa and A. Porrum against iron overload in rat model was reported. Significant decrease in serum ferritin and iron concentration was reported in iron overload rats which induced by iron dextran. PMID- 26153215 TI - Homozygosity mapping and whole-genome sequencing reveals a deep intronic PROM1 mutation causing cone-rod dystrophy by pseudoexon activation. AB - Several genes have been implicated in the autosomal recessive form of cone-rod dystrophy (CRD), but the majority of cases remain unsolved. We identified a homozygous interval comprising two known genes associated with the autosomal recessive form of CRD, namely RAB28 and PROM1, in a consanguineous family with clinical evidence of CRD. Both genes proved to be mutation negative upon sequencing of exons and canonical splice sites but whole-genome sequencing revealed a private variant located deep in intron 18 of PROM1. In silico and functional analyses of this variant using minigenes as splicing reporters revealed the integration of a pseudoexon in the mutant transcript, thereby leading to a premature termination codon and presumably resulting in a functional null allele. This is the first report of a deep intronic variant that acts as a splicing mutation in PROM1. The detection of such variants escapes the exon focused techniques typically used in genetic analyses. Sequencing the entire genomic regions of known disease genes might identify more causal mutations in the autosomal recessive form of CRD. PMID- 26153216 TI - Loss-of-function variants in HIVEP2 are a cause of intellectual disability. AB - Intellectual disability (ID) affects 2-3% of the population. In the past, many genetic causes of ID remained unidentified due to its vast heterogeneity. Recently, whole exome sequencing (WES) studies have shown that de novo variants underlie a significant portion of sporadic cases of ID. Applying WES to patients with ID or global developmental delay at different centers, we identified three individuals with distinct de novo variants in HIVEP2 (human immunodeficiency virus type I enhancer binding protein), which belongs to a family of zinc-finger containing transcriptional proteins involved in growth and development. Two of the variants were nonsense changes, and one was a 1 bp deletion resulting in a premature stop codon that was reported previously without clinical detail. In silico prediction programs suggest loss-of-function in the mutated allele leading to haploinsufficiency as a putative mechanism in all three individuals. All three patients presented with moderate-to-severe ID, minimal structural brain anomalies, hypotonia, and mild dysmorphic features. Growth parameters were in the normal range except for borderline microcephaly at birth in one patient. Two of the patients exhibited behavioral anomalies including hyperactivity and aggression. Published functional data suggest a neurodevelopmental role for HIVEP2, and several of the genes regulated by HIVEP2 are implicated in brain development, for example, SSTR-2, c-Myc, and genes of the NF-kappaB pathway. In addition, HIVEP2-knockout mice exhibit several working memory deficits, increased anxiety, and hyperactivity. On the basis of the genotype-phenotype correlation and existing functional data, we propose HIVEP2 as a causative ID gene. PMID- 26153217 TI - A nonsense variant in HERC1 is associated with intellectual disability, megalencephaly, thick corpus callosum and cerebellar atrophy. AB - Megalencephaly is a congenital condition characterized by severe overdeveloped brain size. This phenotype is often caused by mutations affecting the RTK/PI3K/mTOR (receptor tyrosine kinase-phosphatidylinositol-3-kinase-AKT) signaling and its downstream pathway of mammalian target of rapamycin (mTOR). Here, using a whole-exome sequencing in a Moroccan consanguineous family, we show that a novel autosomal-recessive neurological condition characterized by megalencephaly, thick corpus callosum and severe intellectual disability is caused by a homozygous nonsense variant in the HERC1 gene. Assessment of the primary skin fibroblast from the proband revealed complete absence of the HERC1 protein. HERC1 is an ubiquitin ligase that interacts with tuberous sclerosis complex 2, an upstream negative regulator of the mTOR pathway. Our data further emphasize the role of the mTOR pathway in the regulation of brain development and the power of next-generation sequencing technique in elucidating the genetic etiology of autosomal-recessive disorders and suggest that HERC1 defect might be a novel cause of autosomal-recessive syndromic megalencephaly. PMID- 26153219 TI - Fulminant skin GvHD with a cytokine pattern resemblant of cytokine release syndrome successfully treated with multimodal immunosuppression including tocilizumab. AB - Acute Graft-versus-Host-Disease (GvHD) is a potentially life-threatening complication after allogeneic stem cell transplantation. If not treated early and adequately, the complex immunological mechanisms may lead to a self-perpetuating cycle of alloreactivity, which is then associated with a high mortality. Here we assessed the cytokine profile on a daily basis in a patient with grade 4 skin GvHD, demonstrating a signature resembling cytokine-release-syndrome. After multimodal immunosuppressive intervention, including treatment with the IL6 receptor-blocking antibody tocilizumab, the severe clinical symptoms unexpectedly resolved within 48 hr. PMID- 26153220 TI - What is the best management of asymptomatic unilateral tonsillar enlargement? PMID- 26153218 TI - EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH). AB - Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. The vast majority (typically >90%) of patients with clinically characterized HH are homozygous for the p.C282Y variant in the HFE gene, referred to as HFE related HH. Since 1996, HFE genotyping was implemented in diagnostic algorithms for suspected HH, allowing its early diagnosis and prevention. However, the penetrance of disease in p.C282Y homozygotes is incomplete. Hence, homozygosity for p.C282Y is not sufficient to diagnose HH. Neither is p.C282Y homozygosity required for diagnosis as other rare forms of HH exist, generally referred to as non-HFE-related HH. These pose significant challenges when defining criteria for referral, testing protocols, interpretation of test results and reporting practices. We present best practice guidelines for the molecular genetic diagnosis of HH where recommendations are classified, as far as possible, according to the level and strength of evidence. For clarification, the guidelines' recommendations are preceded by a detailed description of the methodology and results obtained with a series of actions taken in order to achieve a wide expert consensus, namely: (i) a survey on the current practices followed by laboratories offering molecular diagnosis of HH; (ii) a systematic literature search focused on some identified controversial topics; (iii) an expert Best Practice Workshop convened to achieve consensus on the practical recommendations included in the guidelines. PMID- 26153221 TI - Molecular mechanism of a new Laminaria japonica polysaccharide on the suppression of macrophage foam cell formation via regulating cellular lipid metabolism and suppressing cellular inflammation. AB - SCOPE: Laminaria japonica is an important marine vegetable with great health benefits for preventing atherosclerosis. Since the foam cell formation is an important hallmark for the initiation of atherosclerosis, we examined the effect and underlying mechanism of a purified L. japonica polysaccharide (LJP61A) on the suppression of macrophage foam cell formation in this study. The chemical structure was further characterized. METHODS AND RESULTS: Using oxidized low density lipoprotein (ox-LDL)-induced foam cell model, we found that the cellular lipid accumulation was significantly attenuated by 25 MUg/mL LJP61A. Meanwhile, LJP61A caused a remarkable decrease in mRNA expression of peroxisome proliferator activated receptor gamma that was accompanied by the reduction of CD36 and Acyl coenzyme A: cholesterol acyltransferase-1 mRNA levels, and the enhancement of ATP binding cassette transporters A1 and scavenger receptor B1 mRNA levels. Besides these, the ox-LDL-induced cellular inflammation was also restricted by LJP61A treatment via mammalian target of rapamycin-mediated Toll-like receptor 2/4 Mitogen-activated protein kinases/nuclear factor kappa-B pathways. The structure of LJP61A was characterized as a repeating unit consisting of ->3,6)-alpha-d-Manp (1->, ->4)-alpha-d-Manp-(1->, ->4)-2-O-acetyl-beta-d-Glcp-(1->, ->4)-beta-d-Glcp (1->, ->6)-4-O-SO3 -beta-d-Galp-(1->, ->6)-beta-d-Galp-(1->, ->3)-beta-d-Galp-(1 >, and a terminal residue of alpha-d-Glcp-(1->. CONCLUSION: Our findings suggest that LJP61A inhibits the conversion of macrophage into foam cell via regulating cellular lipid metabolism and suppressing cellular inflammation. PMID- 26153223 TI - Colon: a gateway for chronotherapeutic drug delivery systems. AB - Colon-specific delivery systems have attracted considerable attention from the scientific community. One of the distinctions of this site-specific delivery system is its effectiveness in carrying a variety of medicinal agents (required for both localized diseases and systemic therapy). It has been proposed that the biological rhythm of the body may affect the normal physiological as well as biological functions. Diseases such as nocturnal asthma, angina pectoris, inflammation, rheumatoid arthritis, hypertension or cardiac arrhythmia, has been found to follow biological rhythm of the body. For the treatment of these diseases, development of a chronotherapeutic drug delivery system (CrDDS), which delivers a defined dose, at a selected time and chosen rate, and to a targeted site is required. Several CrDDSs have been developed by using various strategies (pH-, time-, microflora-triggered and pressure-controlled systems) with the aim of achieving colon-specific drug delivery. This Editorial article aims to highlight some of the recent advancements that have emerged in the field of colon targeted drug delivery systems pertaining to the chronotherapy of certain disease conditions. PMID- 26153222 TI - Similar but not the same: insights into the evolutionary history of paralogous sex-determining genes of the dwarf honey bee Apis florea. AB - Studying the fate of duplicated genes provides informative insight into the evolutionary plasticity of biological pathways to which they belong. In the paralogous sex-determining genes complementary sex determiner (csd) and feminizer (fem) of honey bee species (genus Apis), only heterozygous csd initiates female development. Here, the full-length coding sequences of the genes csd and fem of the phylogenetically basal dwarf honey bee Apis florea are characterized. Compared with other Apis species, remarkable evolutionary changes in the formation and localization of a protein-interacting (coiled-coil) motif and in the amino acids coding for the csd characteristic hypervariable region (HVR) are observed. Furthermore, functionally different csd alleles were isolated as genomic fragments from a random population sample. In the predicted potential specifying domain (PSD), a high ratio of piN/piS=1.6 indicated positive selection, whereas signs of balancing selection, commonly found in other Apis species, are missing. Low nucleotide diversity on synonymous and genome-wide, non coding sites as well as site frequency analyses indicated a strong impact of genetic drift in A. florea, likely linked to its biology. Along the evolutionary trajectory of ~30 million years of csd evolution, episodic diversifying selection seems to have acted differently among distinct Apis branches. Consistently low amino-acid differences within the PSD among pairs of functional heterozygous csd alleles indicate that the HVR is the most important region for determining allele specificity. We propose that in the early history of the lineage-specific fem duplication giving rise to csd in Apis, A. florea csd stands as a remarkable example for the plasticity of initial sex-determining signals. PMID- 26153224 TI - In vivo investigation of acidified pepsin exposure to porcine vocal fold epithelia. AB - OBJECTIVES/HYPOTHESIS: The study objective was to investigate epithelial changes in response to direct, repeated, acidified pepsin exposures in an in vivo porcine model. We hypothesized that 12 acidified pepsin applications to simulate reflux would elicit a vocal fold response characterized by inflammation, epithelial proliferation, and increased intercellular space, as well as changes in the gene expression of epithelial junctional proteins, ion transporter proteins, and proinflammatory cytokines. STUDY DESIGN: Prospective, in vivo study. METHODS: Pigs received acidified pepsin (pH = 4) or saline (sham) applied directly to vocal folds. Larynges were collected following three exposures per week for 4 weeks. Vocal fold tissue morphology, collagen, and elastin were evaluated histologically. Gene expression of E-cadherin, zona occludens-1, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, interleukin 1beta, tumor necrosis factor-alpha, and interferon-gamma were measured. Ultrastructural alterations, epithelial intercellular space diameter, and microridge height were measured using transmission electron microscopy. RESULTS: There were no significant differences in histology, gene transcripts, epithelial ultrastructure, intercellular space, and microridge height after acidified pepsin exposure. CONCLUSIONS: Twelve simulated reflux challenges were insufficient to elicit epithelial changes, demonstrating the resistance of healthy vocal folds to direct, repeated acidified pepsin exposures. These data increase our understanding of healthy vocal fold defenses and lay the groundwork for a prospective, uninjured, nonsurgical, laryngopharyngeal reflux model where pigs can be exposed directly to acidified pepsin. PMID- 26153225 TI - Transmutation of Personal Glucose Meters into Portable and Highly Sensitive Microbial Pathogen Detection Platform. AB - Herein, for the first time, we presented a simple and general approach by using personal glucose meters (PGM) for portable and ultrasensitive detection of microbial pathogens. Upon addition of pathogenic bacteria, glucoamylase quaternized magnetic nanoparticles (GA-QMNPS) conjugates were disrupted by the competitive multivalent interactions between bacteria and QMNPS, resulting in the release of GA. After magnetic separation, the free GA could catalyze the hydrolysis of amylose into glucose for quantitative readout by PGM. In such way, PGM was transmuted into a bacterial detection device and extremely low detection limits down to 20 cells mL(-1) was achieved. More importantly, QMNPS could inhibit the growth of the bacteria and destroy its cellular structure, which enabled bacteria detection and inhibition simultaneously. The simplicity, portability, sensitivity and low cost of presented work make it attractive for clinical applications. PMID- 26153226 TI - Emerging immunological drugs for chronic lymphocytic leukemia. AB - INTRODUCTION: Over the last few years, several new immunological drugs, particularly monoclonal antibodies (mAbs), immunomodulatory drugs and B-cell receptor (BCR) pathway inhibitors have been developed and investigated in chronic lymphocytic leukemia (CLL). This article summarizes recent discoveries regarding their mechanism of action, pharmacological properties, clinical activity and toxicity, as well as the emerging role of these agents in CLL. AREAS COVERED: A literature review of mAbs, BCR pathway inhibitors and immunomodulating drugs was conducted of the MEDLINE database via PubMed for articles in English. Publications from 2000 through February 2015 were scrutinized. The search terms used were alemtuzumab, BI 836826, duvelisib ibrutinib, idelalisib, lenalidomide, monoclonal antibodies, MEDI-551, MOR208, obinutuzumab, ocaratuzumab, ofatumumab, ONO-4059, otlertuzumab, spebrutinib, veltuzumab and XmAb5574 in conjunction with CLL. Conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. EXPERT OPINION: The use of mAbs, BCR inhibitors and immunomodulating drugs is a promising new strategy for chemotherapy-free treatment of CLL. However, definitive data from ongoing and future clinical trials will aid in better defining the status of immunological drugs in the treatment of this disease. PMID- 26153227 TI - High-Performance Flexible Organic Nano-Floating Gate Memory Devices Functionalized with Cobalt Ferrite Nanoparticles. AB - Nano-floating gate memory (NFGM) devices are transistor-type memory devices that use nanostructured materials as charge trap sites. They have recently attracted a great deal of attention due to their excellent performance, capability for multilevel programming, and suitability as platforms for integrated circuits. Herein, novel NFGM devices have been fabricated using semiconducting cobalt ferrite (CoFe2O4) nanoparticles (NPs) as charge trap sites and pentacene as a p type semiconductor. Monodisperse CoFe2O4 NPs with different diameters have been synthesized by thermal decomposition and embedded in NFGM devices. The particle size effects on the memory performance have been investigated in terms of energy levels and particle-particle interactions. CoFe2O4 NP-based memory devices exhibit a large memory window (~73.84 V), a high read current on/off ratio (read I(on)/I(off)) of ~2.98 * 10(3), and excellent data retention. Fast switching behaviors are observed due to the exceptional charge trapping/release capability of CoFe2O4 NPs surrounded by the oleate layer, which acts as an alternative tunneling dielectric layer and simplifies the device fabrication process. Furthermore, the NFGM devices show excellent thermal stability, and flexible memory devices fabricated on plastic substrates exhibit remarkable mechanical and electrical stability. This study demonstrates a viable means of fabricating highly flexible, high-performance organic memory devices. PMID- 26153228 TI - Confocal microscopy evaluation of the effect of irrigants on Enterococcus faecalis biofilm: An in vitro study. AB - The purpose of this study was to evaluate in vitro the effectiveness of two endodontic irrigants and their association against Enterococcus faecalis (E. faecalis) by confocal laser scanning microscope (CLSM). Twenty-four bovine incisors were inoculated in a monoculture of E. faecalis for 21 days. After this period, the teeth were divided into three test groups (n = 5) according to the chemical used. Group 1: 2.5% sodium hypochlorite (NaOCl), group 2: 2% chlorhexidine gel (CHX), group 3: 2.5% NaOCl + 2% CHX gel, and two control groups (n = 3): negative control group (NCG)-sterile and without root canals preparation and positive control group (PCG)-saline. Then, the samples were stained with SYTO9 and propidium iodide and subjected to analysis by CLSM. Bacterial viability was quantitatively analyzed by the proportions of dead and live bacteria in the biofilm remnants. Statistical analysis was performed by the One-way ANOVA test (p = 0.05). No statistical differences were observed to bacterial viability. According to CLSM analysis, none of the tested substances could completely eliminate E. faecalis from the root canal space. Until now, there are no irrigant solutions able to completely eliminate E. faecalis from the root canal. In this regard, the search for irrigants able to intensify the antimicrobial action is of paramount importance. PMID- 26153231 TI - An interview with Brigid Hogan. AB - Brigid Hogan is a developmental biologist who has worked extensively on the early stages of mouse development and is now unravelling the mysteries of lung organogenesis. She is the George Barth Geller Professor and Chair of the Department of Cell Biology at Duke University Medical Center. Brigid is also the winner of the 2015 Society for Developmental Biology (SDB) Lifetime Achievement Award. PMID- 26153229 TI - Inhibition of beta-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes. AB - During vertebrate development, mesodermal fate choices are regulated by interactions between morphogens such as activin/nodal, BMPs and Wnt/beta-catenin that define anterior-posterior patterning and specify downstream derivatives including cardiomyocyte, endothelial and hematopoietic cells. We used human embryonic stem cells to explore how these pathways control mesodermal fate choices in vitro. Varying doses of activin A and BMP4 to mimic cytokine gradient polarization in the anterior-posterior axis of the embryo led to differential activity of Wnt/beta-catenin signaling and specified distinct anterior-like (high activin/low BMP) and posterior-like (low activin/high BMP) mesodermal populations. Cardiogenic mesoderm was generated under conditions specifying anterior-like mesoderm, whereas blood-forming endothelium was generated from posterior-like mesoderm, and vessel-forming CD31(+) endothelial cells were generated from all mesoderm origins. Surprisingly, inhibition of beta-catenin signaling led to the highly efficient respecification of anterior-like endothelium into beating cardiomyocytes. Cardiac respecification was not observed in posterior-derived endothelial cells. Thus, activin/BMP gradients specify distinct mesodermal subpopulations that generate cell derivatives with unique angiogenic, hemogenic and cardiogenic properties that should be useful for understanding embryogenesis and developing therapeutics. PMID- 26153230 TI - HIF modulation of Wnt signaling regulates skeletal myogenesis in vivo. AB - Deeper insight into the molecular pathways that orchestrate skeletal myogenesis should enhance our understanding of, and ability to treat, human skeletal muscle disease. It is now widely appreciated that nutrients, such as molecular oxygen (O2), modulate skeletal muscle formation. During early stages of development and regeneration, skeletal muscle progenitors reside in low O2 environments before local blood vessels and differentiated muscle form. Moreover, low O2 availability (hypoxia) impedes progenitor-dependent myogenesis in vitro through multiple mechanisms, including activation of hypoxia inducible factor 1alpha (HIF1alpha). However, whether HIF1alpha regulates skeletal myogenesis in vivo is not known. Here, we explored the role of HIF1alpha during murine skeletal muscle development and regeneration. Our results demonstrate that HIF1alpha is dispensable during embryonic and fetal myogenesis. However, HIF1alpha negatively regulates adult muscle regeneration after ischemic injury, implying that it coordinates adult myogenesis with nutrient availability in vivo. Analyses of Hif1a mutant muscle and Hif1a-depleted muscle progenitors further suggest that HIF1alpha represses myogenesis through inhibition of canonical Wnt signaling. Our data provide the first evidence that HIF1alpha regulates skeletal myogenesis in vivo and establish a novel link between HIF and Wnt signaling in this context. PMID- 26153232 TI - The Drosophila planar polarity gene multiple wing hairs directly regulates the actin cytoskeleton. AB - The evolutionarily conserved frizzled/starry night (fz/stan) pathway regulates planar cell polarity (PCP) in vertebrates and invertebrates. This pathway has been extensively studied in the Drosophila wing, where it is manifested by an array of distally pointing cuticular hairs. Using in vivo imaging we found that, early in hair growth, cells have multiple actin bundles and hairs that subsequently fuse into a single growing hair. The downstream PCP gene multiple wing hairs (mwh) plays a key role in this process and acts to antagonize the actin cytoskeleton. In mwh mutants hair initiation is not limited to a small region at the distal edge of pupal wing cells as in wild type, resulting in multiple hairs with aberrant polarity. Extra actin bundles/hairs are formed and do not completely fuse, in contrast to wild type. As development proceeded additional hairs continued to form, further increasing hair number. We identified a fragment of Mwh with in vivo rescue activity and that bound and bundled F-actin filaments and inhibited actin polymerization in in vitro actin assays. The loss of these activities can explain the mwh mutant phenotype. Our data suggest a model whereby, prior to hair initiation, proximally localized Mwh inhibits actin polymerization resulting in polarized activation of the cytoskeleton and hair formation on the distal side of wing cells. During hair growth Mwh is found in growing hairs, where we suggest it functions to promote the fusion of actin bundles and inhibit the formation of additional actin bundles that could lead to extra hairs. PMID- 26153234 TI - Voice- and swallow-related quality of life in idiopathic Parkinson's disease. AB - OBJECTIVES/HYPOTHESIS: This study explores whether changes in voice- and swallow related QoL are associated with progression of idiopathic Parkinson's disease (IPD). Furthermore, it examines the relationship between patients' perception of both voice and swallowing disorders in IPD. STUDY DESIGN: Prospective clinical study, quality of life (QoL). METHODS: One-hundred mentally competent IPD patients with voice and swallowing complaints were asked to answer four QoL questionnaires (Voice Handicap Index, MD Anderson Dysphagia Inventory, Visual Analog Scale [VAS] voice, and Dysphagia Severity Scale [DSS]). Differences in means for the QoL questionnaires and their subscales within Hoehn and Yahr stage groups were calculated using one-way analysis of variance. The relationship between voice- and swallow-related QoL questionnaires was determined with the Spearman correlation coefficient. RESULTS: Scores on both voice and swallow questionnaires suggest an overall decrease in QoL with progression of IPD. A plateau in QoL for VAS voice and the DSS was seen in the early Hoehn and Yahr stages. Finally, scores on voice-related QoL questionnaires were significantly correlated with swallow-related QoL outcomes. CONCLUSIONS: Voice- and swallow related QoL decreases with progression of IPD. A significant association was found between voice- and swallow-related QoL questionnaires. Healthcare professionals can benefit from voice- and swallow-related QoL questionnaires in a multidimensional voice- or swallow-assessment protocol. The patient's perception of his/her voice and swallowing disorders and its impact on QoL in IPD should not be disregarded. LEVEL OF EVIDENCE: 2b. PMID- 26153233 TI - C. elegans SoxB genes are dispensable for embryonic neurogenesis but required for terminal differentiation of specific neuron types. AB - Neurogenesis involves deeply conserved patterning molecules, such as the proneural basic helix-loop-helix transcription factors. Sox proteins and specifically members of the SoxB and SoxC groups are another class of conserved transcription factors with an important role in neuronal fate commitment and differentiation in various species. In this study, we examine the expression of all five Sox genes of the nematode C. elegans and analyze the effect of null mutant alleles of all members of the SoxB and SoxC groups on nervous system development. Surprisingly, we find that, unlike in other systems, neither of the two C. elegans SoxB genes sox-2 (SoxB1) and sox-3 (SoxB2), nor the sole C. elegans SoxC gene sem-2, is broadly expressed throughout the embryonic or adult nervous system and that all three genes are mostly dispensable for embryonic neurogenesis. Instead, sox-2 is required to maintain the developmental potential of blast cells that are generated in the embryo but divide only postembryonically to give rise to differentiated neuronal cell types. Moreover, sox-2 and sox-3 have selective roles in the terminal differentiation of specific neuronal cell types. Our findings suggest that the common themes of SoxB gene function across phylogeny lie in specifying developmental potential and, later on, in selectively controlling terminal differentiation programs of specific neuron types, but not in broadly controlling neurogenesis. PMID- 26153235 TI - Emerging treatment for advanced lung cancer with EGFR mutation. AB - INTRODUCTION: Lung cancer is the leading cause of cancer-related death worldwide. It is usually diagnosed at advanced stage for which platinum-based chemotherapy had been the standard approach, although with limited clinical benefits. Discovery of oncogenic EGFR mutations in lung cancer have shifted the treatment paradigm with molecularly targeted therapies. AREAS COVERED: EGFR tyrosine kinase inhibitors (TKIs) have become the first-line choice in patients with advanced NSCLC harboring EGFR activating mutations. However, resistance to targeted therapy develops inevitably during the course of treatment. Multiple mechanisms of acquired resistance have been discovered, most commonly the secondary mutation of T790M in exon 20. The second- and third-generation EGFR TKIs are holding promise to overcome T790M-associated acquired resistance and currently being tested in clinical trials. In this article, we focus on the emerging approaches to overcome the different mechanisms of resistance to targeted therapies in patients with EGFR-mutant advanced NSCLC. EXPERT OPINION: It is essential to uncover the complex mechanisms underlying the progression of lung cancer after upfront EGFR TKIs. Next generation, in particular, the third generations of EGFR TKIs have been developed against acquired T790M mutation with promising clinical activity and better toxicity profile. Combination of targeted therapies has also been explored. Further studies are needed to detect the real-time changes of the resistance mechanisms and to develop new therapeutic strategies for lung cancer patients with EGFR mutations. PMID- 26153236 TI - Effects of membrane lipid composition and antibacterial drugs on the rigidity of Escherichia coli: Different contributions of various bacterial substructures. AB - The rigidity/stiffness is an important biomechanical property of bacteria and potentially correlated with many bacterial activities. While the rigidity or fluidity of the bacterial membrane has been extensively studied, the contributions of different bacterial substructures to the bacterial rigidity are less investigated. Here, we utilized four Escherichia coli (E. coli) strains with different membrane lipid compositions and three antibacterial drugs (EDTA, lysozyme, and streptomycin) to specifically alter bacterial substructures. By using atomic force microscopy (AFM), we found that the average height and Young's modulus of phosphatidylethanolamine (PE)-deficient E. coli strains were larger than those of PE(+) strains and that EDTA, EDTA plus lysozyme instead of lysozyme alone, and streptomycin all caused significant decreases in height and Young's modulus of the four E. coli strains. Our data imply that membrane lipid composition, the integrated outer membrane, the cell wall, and the cytoplasmic content are all responsible for bacterial rigidity but to different extents. PMID- 26153237 TI - Emerging drugs for the treatment of myelofibrosis. AB - INTRODUCTION: Myelofibrosis (MF) is a myeloproliferative neoplasm associated with significant disease burden composed of splenomegaly, constitutional symptoms and a reduced life expectancy. The advent of targeted treatments has provided new means by which to improve MF associated splenomegaly, symptoms, health-related quality of life and even mortality. AREAS COVERED: We discuss the spectrum of targeted treatments currently under investigation for MF. We furthermore compare their effects on improving anemia, reducing fibrosis and splenomegaly and enhancing symptom control. EXPERT OPINION: MF is a complex disorder, partly attributable to its heterogeneity. Although the severity of patient symptoms correlates with risk category, high symptom burden may also be observed in low risk patients. Serial use of PRO tools allows clinicians to objectively evaluate the MF symptom burden, compare efficacy of therapies and adjust medications to improve symptom control. Novel targeted agents have proven superior to historic treatment regimens for symptom management. Promising treatment categories include JAK2 inhibitors, histone deacetylase inhibitors, hypomethylating agents, heat shock protein-90 inhibitors, hedgehog inhibitors, PI3-AKT-mTOR inhibitors, antifibrosing agents and telomerase inhibitors. The majority of therapies remain under investigation, either alone or in combination with other treatments. It is anticipated that these agents will be increasingly integrated into standard treatment algorithms for MF symptom management. PMID- 26153238 TI - Use of telehealth videoconferencing as a supplement to visiting allied health services. PMID- 26153239 TI - Structure-activity relationship studies on 1-heteroaryl-3-phenoxypropan-2-ones acting as inhibitors of cytosolic phospholipase A2alpha and fatty acid amide hydrolase: replacement of the activated ketone group by other serine traps. AB - Cytosolic phospholipase A2alpha (cPLA2alpha) and fatty acid amide hydrolase (FAAH) are serine hydrolases. cPLA2alpha is involved in the generation of pro inflammatory lipid mediators, FAAH terminates the anti-inflammatory effects of endocannabinoids. Therefore, inhibitors of these enzymes may represent new drug candidates for the treatment of inflammation. We have reported that certain 1 heteroarylpropan-2-ones are potent inhibitors of cPLA2alpha and FAAH. The serine reactive ketone group of these compounds, which is crucial for enzyme inhibition, is readily metabolized resulting in inactive alcohol derivatives. In order to obtain metabolically more stable inhibitors, we replaced this moiety by alpha ketoheterocyle, cyanamide and nitrile serine traps. Investigations on activity and metabolic stability of these substances revealed that in all cases an increased metabolic stability was accompanied by a loss of inhibitory potency against cPLA2alpha and FAAH, respectively. PMID- 26153240 TI - Who are they and what do they do? Profile of allied health professionals working with people with disabilities in rural and remote New South Wales. AB - OBJECTIVE: To explore the characteristics of allied health professionals (AHPs) working with people with disabilities in western New South Wales (NSW). DESIGN: A cross-sectional survey was conducted using an online questionnaire. SETTING: Rural western NSW. PARTICIPANTS: AHPs including physiotherapists, speech pathologists, occupational therapists and psychologists ('therapists') working with people with disabilities. MAIN OUTCOME MEASURE: AHPs characteristics. RESULTS: The majority of respondents were women (94%), with a mean age of 39 years; average time since qualification was 14 years; mean years in current position was 6. Most worked with people with a lifelong disability. Two thirds reported that family ties kept them in rural areas; 71% grew up in a rural/remote area. Most participants (94%) enjoyed the rural lifestyle, and 84% reported opportunities for social interaction as good or very good. Participants with dependent children were less likely to cease working in western NSW within 5 years than those without dependent children (P < 0.05). CONCLUSIONS: The characteristics of therapists working with people with disabilities in rural NSW were identified. Overall working, but also social conditions and community attachment were important for this group. Understanding the workforce will contribute to policy development to meet increasing demands for therapy services. PMID- 26153241 TI - Evaluation of the SIGNIFY trial. AB - A reduction in the heart rate has been thought to be beneficial in coronary artery disease. The study assessing the morbidity-mortality Benefits of the If Inhibitor, Ivabradine, in patients with coronary artery disease (SIGNIFY) tested this hypothesis. It specifically evaluated the effects of ivabradine, administered at the dosage of 5 - 10 mg/bid in addition to current drug treatment, on cardiovascular outcome in 19102 patients with heart rate >= 70 bpm in normal sinus rhythm and stable coronary artery disease without heart failure. The primary endpoint of the trial, whose follow-up averaged for 2.3 years, was a composite of death from cardiovascular causes or nonfatal myocardial infarction whereas the secondary endpoint was represented by the primary endpoint plus total mortality. The incidence of the primary endpoint was at the study end similar in the ivabradine-treated and in the placebo-treated group (6.8 vs 6.4%, p = NS). Superimposable was also the incidence of death for cardiovascular events and for nonfatal myocardial infarction. However, in the 12049 patients with angina class II or higher ivabradine significantly increased the incidence of primary endpoint as compared to placebo (7.6 vs 6.5%, p < 0.02). This was associated with a significantly greater incidence of bradycardia, atrial fibrillation and Q-T prolongation. Taken together the results of the SIGNIFY do not support the clinical benefits of ivabradine in patients with stable coronary artery disease. PMID- 26153242 TI - Peramivir: an intravenous neuraminidase inhibitor. AB - INTRODUCTION: Peramivir (BCX-1812, RWJ-270201) is a highly selective inhibitor of influenza A and B neuraminidase that has recently been approved in the USA by the FDA to treat acute, uncomplicated influenza in adults. AREAS COVERED: This review examines the discovery and development of peramavir as well as its role in the treatment of influenza. Peramivir is currently the only FDA-approved anti influenza agent that can be given as an intravenous injection, granting it a unique role in therapy with the potential to improve adherence and outcomes in patients who are unable to tolerate oral agents. In vitro, animal, human and safety data are presented as well as information regarding special populations, resistance and drug approval. EXPERT OPINION: Clinical trial data support the use of peramivir to relieve influenza symptoms in acute, uncomplicated influenza, with improvements over placebo similar to those of other approved anti-influenza treatments. The ability to give a one-time injectable dose offers improved adherence over currently available oral regimens. While not approved for hospitalized patients, available data suggest that multiple dose peramivir may also have a role in treatment of severally ill, hospitalized patients. Supportive data for the use of peramivir in special patient populations such as pediatrics and those especially at-risk to develop severe influenza symptoms are promising; however, they require further study. PMID- 26153243 TI - Histopathological effect of balloon dilation in a live rabbit: Implications for the pediatric airway. AB - OBJECTIVE/HYPOTHESIS: To examine the short- and long-term histopathologic changes that occur in the subglottis in response to airway balloon dilation (ABD) with different balloon diameters and inflation pressures. STUDY DESIGN: Prospective animal study using forty-two 8-month old New Zealand white rabbits at an academic animal research facility. METHODS: Thirty-nine live New Zealand rabbits underwent a single ABD with diameters ranging from 6.0 mm to 10.0 mm and with pressures between 5.0 atmospheres (atm) to 15.0 atm. Animals were euthanized on postoperative days (POD) 1, 7, and 30, and the histopathological changes of the subglottis were examined. Three rabbits served as controls and underwent no ABD. RESULTS: The subglottic airway diameter of all specimens measured 5.4 mm. When examining the fracture rate by balloon diameter, we found the following: 0 of 6 (0%) at 6 mm, 0 of 9 (0%) at 7 mm, 6 of 9 (67%) at 8 mm, 8 of 9 (89%) at 9 mm, and 6 of 6 (100%) at 10 mm. There was a statistically significant relationship with the rate of cricoid fracture as balloon diameter increased (P < .0001). All fractures occurred at the anterior cricoid lamina. On POD 1, we found mild ulceration in 5 of 6 (83%) using a 6-mm or 7-mm balloon and in 0 of 6 (0%) using an 8-mm, 9-mm, or 10-mm balloon; and moderate/severe ulceration in 1 of 6 (16.67%) using a 6-mm or 7-mm balloon and in 11 of 11 (100%) using an 8-mm, 9-mm, or 10-mm balloon (P < .0001). Also on POD 1, we found mild edema in 6 of 6 (100%) using a 6-mm or 7-mm balloon and in 5 of 11 (45%) using an 8-mm, 9-mm, or 10-mm balloon; and moderate/severe edema in 0 of 6 (0%) using a 6-mm/7-mm balloon and in 6 of 11 (55%) using an 8-mm, 9-mm, or 10-mm balloon (P =.048). On POD 7, we found fibroplasia in 5 of 6 (83%) using a 6-mm or 7-mm balloon and in 1 of 7 (14%) using an 8-mm, 9-mm, or 10-mm balloon; and moderate/severe fibroplasia in 1 of 6 (17%) using a 6-mm or 7-mm balloon and in 6 of 7 (86%) using an 8-mm, 9-mm, or 10-mm balloon (P =.029). Also on POD7, we found granulation tissue in 0 of 6 (0%) using a 6-mm or 7-mm balloon and in 5 of 7 (71%) using an 8-mm, 9-mm, or 10 mm balloon (P = .021). On POD 30, we found no fibrosis in 0 of 3 (0%) using a 7 mm balloon, mild fibrosis in 1 of 6 (16.67%), and moderate/severe fibrosis in 5 of 6 (83%) using an 8-mm or 9-mm balloon (P = .048). Also on POD 30, we found the mean subglottic cross-sectional luminal area was 23.79 mm(2) with a 7-mm balloon and 29.28 mm(2) with an 8-mm or 9-mm balloon (P = .019). Inflation pressure alone had no correlation with mucosal injury or probability of cricoid fracture. CONCLUSIONS: Airway balloon dilation with balloon diameters that exceeded the airway diameter by 2.6 mm was associated with cricoid fractures. All cricoid fractures localized to the anterior cricoid lamina. Balloon diameters larger than the airway diameter by 2.6 mm resulted in a larger subglottic cross-sectional luminal area on POD 30. Airway balloon dilation with balloon diameters that could generate a cricoid fracture created more mucosal injury on POD 0, 1, and 7 than smaller balloon diameters. The histopathological effects of airway balloon dilation observed on POD 0, 1, and 7 resolved by POD 30. When balloon diameter is kept constant, inflation pressure alone had no correlation with mucosal injury or probability of cricoid fracture. LEVEL OF EVIDENCE: NA (animal study). Laryngoscope, 125:S1-S11, 2015. PMID- 26153244 TI - The Cu2O2 torture track for a real-life system: [Cu2(btmgp)2O2](2+) oxo and peroxo species in density functional calculations. AB - Density functional theory (DFT) calculations of the equilibrium geometry, vibrational modes, ionization energies, electron affinities, and optical response of [Cu2(btmgp)2(MU-O)2](2+) (oxo) and [Cu2(btmgp)2(MU-eta(2):eta(2)-O2)](2+) (peroxo) are presented. Comprehensive benchmarking shows that the description of the oxo-peroxo energetics is still a torture track for DFT, but finds the molecular geometry to be comparatively robust with respect to changes in the exchange-correlation functionals and basis sets. Pure functionals favor the oxo core found experimentally, whereas hybrid functionals shift the bias toward the peroxo core. Further stabilization of peroxo core results from relaxing the spin degrees of freedom using the broken-symmetry (BS) approach. Dispersion effects, conversely, tend to favor the oxo configuration. Triple-zeta basis sets are found to represent a sensible compromise between numerical accuracy and computational effort. Particular attention is paid to the modification of the electronic structure, optical transitions, and excited-state energies along the transition path between the oxo and peroxo species. The excited-state potential energy surface calculations indicate that two triplet states are involved in the transition that stabilize the BS solution. Charge decomposition and natural transition orbital analyses are used for obtaining microscopic insight into the molecular orbital interactions. Here, the crucial role of guanidine pi interactions is highlighted for the stabilization of the Cu2O2 core. PMID- 26153245 TI - Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease. AB - Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (?LDLR, ?MYLIP), synthesis (?SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (?ABCA1, ABCG1), producing a molecular profile expected to increase intracellular cholesterol. Importantly, these alterations were associated with T2D and coronary artery calcium (CAC), independent from cardiometabolic factors, including serum lipid profiles. This network mediated the associations between obesity and T2D/CAC. Several genes in the network harbored C-phosphorus-G dinucleotides (e.g., ABCG1/cg06500161), which overlapped Encyclopedia of DNA Elements (ENCODE) annotated regulatory regions and had methylation profiles that mediated the associations between BMI/inflammation and expression of their cognate genes. Taken together with several lines of previous experimental evidence, these data suggest that alterations of the cholesterol metabolism gene network represent a molecular link between obesity/inflammation and T2D/CAC. PMID- 26153248 TI - Controversy in the link between vitamin D supplementation and hypertension. AB - Vitamin D affects a range of pathophysiological processes pertinent to the control of blood pressure, including endothelial function, inflammation and renin angiotensin system activity. Observational data show a clear relationship between 25-hydroxyvitamin D levels and both current blood pressure and incident hypertension. However, recent trial data have shown no significant effect of vitamin D supplementation on blood pressure, even at high doses, low vitamin D levels and in patients with high baseline blood pressure. Vitamin D might still benefit cardiovascular health through mechanisms other than blood pressure reduction, but data from large trials are required to show this. In the meantime, vitamin D has no place in controlling blood pressure either at the individual or the population level. PMID- 26153246 TI - Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone. AB - There is growing concern over confounding artifacts associated with beta-cell specific Cre-recombinase transgenic models, raising questions about their general usefulness in research. The inducible beta-cell-specific transgenic (MIP CreERT(1Lphi)) mouse was designed to circumvent many of these issues, and we investigated whether this tool effectively addressed concerns of ectopic expression and disruption of glucose metabolism. Recombinase activity was absent from the central nervous system using a reporter line and high-resolution microscopy. Despite increased pancreatic insulin content, MIP-CreERT mice on a chow diet exhibited normal ambient glycemia, glucose tolerance and insulin sensitivity, and appropriate insulin secretion in response to glucose in vivo and in vitro. However, MIP-CreERT mice on different genetic backgrounds were protected from high-fat/ streptozotocin (STZ)-induced hyperglycemia that was accompanied by increased insulin content and islet density. Ectopic human growth hormone (hGH) was highly expressed in MIP-CreERT islets independent of tamoxifen administration. Circulating insulin levels remained similar to wild-type controls, whereas STZ-associated increases in alpha-cell number and serum glucagon were significantly blunted in MIP-CreERT(1Lphi) mice, possibly due to paracrine effects of hGH-induced serotonin expression. These studies reveal important new insight into the strengths and limitations of the MIP-CreERT mouse line for beta-cell research. PMID- 26153247 TI - Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration. AB - Diabetes is associated with a paucity of insulin-producing beta-cells. With the goal of finding therapeutic routes to treat diabetes, we aim to find molecular and cellular mechanisms involved in beta-cell neogenesis and regeneration. To facilitate discovery of such mechanisms, we use a vertebrate organism where pancreatic cells readily regenerate. The larval zebrafish pancreas contains Notch responsive progenitors that during development give rise to adult ductal, endocrine, and centroacinar cells (CACs). Adult CACs are also Notch responsive and are morphologically similar to their larval predecessors. To test our hypothesis that adult CACs are also progenitors, we took two complementary approaches: 1) We established the transcriptome for adult CACs. Using gene ontology, transgenic lines, and in situ hybridization, we found that the CAC transcriptome is enriched for progenitor markers. 2) Using lineage tracing, we demonstrated that CACs do form new endocrine cells after beta-cell ablation or partial pancreatectomy. We concluded that CACs and their larval predecessors are the same cell type and represent an opportune model to study both beta-cell neogenesis and beta-cell regeneration. Furthermore, we show that in cftr loss-of function mutants, there is a deficiency of larval CACs, providing a possible explanation for pancreatic complications associated with cystic fibrosis. PMID- 26153249 TI - Recurrent laryngeal nerve alterations in developing spontaneously hypertensive rats. AB - OBJECTIVES/HYPOTHESIS: It is well known that the recurrent laryngeal nerve not only innervates the larynx but also contains baroreceptor fibers, as demonstrated by physiological studies. Because hypertension has a negative impact on both peripheral nerve morphology and the baroreflex, we investigated the recurrent laryngeal nerve morphological alterations related to the development of hypertension. METHODS: We compared morphological and morphometric aspects of different segments of the recurrent laryngeal nerve in male and female spontaneously hypertensive rats in different ages: 5, 8, and 20 weeks (n = 6 per group). Blood pressure and heart rate were recorded in anesthetized animals, followed by removal of the right and left recurrent laryngeal nerves for epoxy resin embedding and light microscopy analysis. Computer software was used for morphometric analysis. RESULTS: The blood pressure was significantly higher in 20 week-old animals compared to those at 5 weeks. Body weight increased significantly with age, as did the nerve fascicles. For the myelinated fibers and respective axons, there was a reduction of fiber size, more evident on the axon, associated with a reduction of the small myelinated fibers percentage in animals with high blood pressure. Also, 20-week-old animals showed a significant reduction of the blood vessel percentage of occupancy compared to younger ages. No differences were observed between genders. CONCLUSION: Hypertension development impaired axon growth, affecting mainly the small myelinated fibers. Males and females were affected equally. The alterations of the endoneural blood vessels probably played an important role on the small fibers alterations. PMID- 26153250 TI - Viewing Majorana Bound States by Rabi Oscillations. AB - We propose to use Rabi oscillation as a probe to view the fractional Josepshon relation (FJR) associated with Majorana bound states (MBSs) expected in one dimensional topological superconductors. The system consists of a quantum dot (QD) and an rf-SQUID with MBSs at the Josephson junction. Rabi oscillations between energy levels formed by MBSs are induced by ac gate voltage controlling the coupling between QD and MBS when the photon energy proportional to the ac frequency matches gap between quantum levels formed by MBSs and QD. As a manifestation of the Rabi oscillation in the whole system involving MBSs, the electron occupation on QD oscillates with time, which can be measured by charge sensing techniques. With Floquet theorem and numerical analysis we reveal that from the resonant driving frequency for coherent Rabi oscillation one can directly map out the FJR cos(piPhi/Phi0) as a signature of MBSs, with Phi the magnetic flux through SQUID and Phi0 = hc/2e the flux quantum. The present scheme is expected to provide a clear evidence for MBSs under intensive searching. PMID- 26153251 TI - Conformation of the Poly(ethylene Glycol) Chains in DiPEGylated Hemoglobin Specifically Probed by SANS: Correlation with PEG Length and in Vivo Efficiency. AB - Cell-free hemoglobin (Hb)-based oxygen carriers have long been proposed as blood substitutes but their clinical use remains tricky due to problems of inefficiency and/or toxicity. Conjugation of Hb with the biocompatible polymer poly(ethylene glycol) (PEG) greatly improved their performance. However, physiological data suggested a polymer molecular weight (Mw) threshold of about 10 kDa, beyond which the grafting of two PEG chains no longer improves efficiency and nontoxicity of diPEG/Hb conjugates. We used small-angle neutron scattering and contrast variation, which are the only techniques able to probe separately the conformation of PEG chains and Hb protein within the complex, to investigate the role of PEG chain conformation in diPEGylated Hb conjugates as a function of the polymer Mw. We found out that the structure of Hb tetramer is not modified by the polymer grafting. Similarly, with a constant grafting of two chains per protein, there is no significant change of the Gaussian conformation between free and grafted PEG below ~10 kDa, the complex being well described by the "dumbbell" model. However, beyond that threshold, the radius of gyration of grafted PEG is significantly smaller than that of the free polymer, showing a compaction of the PEG chains, either in the "dumbbell" model or in the "shroud" one. In the latter model, the polymer may be wrapped on the surface of the protein spreading a protective "shielding" effect over a larger fraction of the protein. Both proposed models are in good agreement with the physiological data reported in the literature. PMID- 26153252 TI - Voice outcomes following reoperative central neck dissection for recurrent/persistent thyroid cancer. AB - OBJECTIVES/HYPOTHESIS: We aimed to assess voice outcomes following reoperative central neck dissection (RCND) to characterize postoperative voice difficulties experienced, determine the natural progression of vocal recovery, and identify risk factors for the development of voice disorders postoperatively. STUDY DESIGN: Prospective cohort study. METHODS: Consecutive patients with recurrent/persistent thyroid cancer who were deemed appropriate candidates for RCND were eligible for participation in this study. A battery of voice evaluation measures was administered both preoperatively and 2 to 4 weeks postoperatively. RESULTS: Twenty consecutive patients were included. Postoperatively, six (30%) new incidents of vocal fold motion impairment (VFMI) were identified, with two (10%) being due to intentional recurrent laryngeal nerve (RLN) transection. On 1 year follow-up, two patients had full restoration of vocal fold mobility and four had persistent VFMI. No preoperative voice/laryngeal exam factors were predictive of postoperative VFMI. Clinically relevant change in postoperative Voice Handicap Index score was absent in all patients without VFMI and present in five of six patients with VFMI (P=.0004). Patients with VFMI had significantly poorer overall dysphonia grade, less glottic closure, and elevated jitter in contrast to those individuals without VFMI. Patients with malignant tissue in the remnant thyroid were four times more likely to develop VFMI than those with central neck lymph node metastases alone (P=.06). CONCLUSION: Patients undergoing RCND are at risk for postoperative VFMI, even when the RLN is anatomically preserved, with subsequent impact on quality of life. Presence of malignant disease in the remnant thyroid appears to be the best predictor for postoperative VFMI. LEVEL OF EVIDENCE: 2b. PMID- 26153253 TI - Pancreaticoduodenectomy for pancreas carcinoma occurring in the annular pancreas: report of a case. AB - The annular pancreas is a rare congenital anomaly in which a ring of the pancreas parenchyma surrounds the second part of the duodenum. Malignant tumors are extremely rare in patients with an annular pancreas. A 64-year-old man presented with appetite loss and vomiting. Abdominal contrast-enhanced computed tomography (CT) indicated pancreas parenchyma surrounding the second part of the duodenum, and a hypovascular area occupying lesion in the annular pancreas. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Histopathology showed pancreatic carcinoma occurring in the complete annular pancreas. PMID- 26153254 TI - Proteolytic Degradation of Bovine Submaxillary Mucin (BSM) and Its Impact on Adsorption and Lubrication at a Hydrophobic Surface. AB - The effects of proteolytic digestion on bovine submaxillary mucin (BSM) were investigated in terms of changes in size, secondary structure, surface adsorption, and lubricating properties. Two proteases with distinctly different cleavage specificities, namely trypsin and pepsin, were employed. SDS-PAGE analysis with staining for proteins and carbohydrate moieties showed that only the unglycosylated terminal regions of BSM were degraded by the proteases. Size exclusion chromatography (SEC) and dynamic light scattering (DLS) analyses indicated that tryptic digestion mainly led to the reduction in size, whereas pepsin digestion rather caused an increase in the size of BSM. Less complete cleavage in terminal peptide regions by pepsin and subsequent aggregation were possibly responsible for the increased size. Far-UV circular dichroism (CD) spectra of the protease-treated BSM showed a slight change in the secondary structure owing to the removal of terminal domains, but the overall random coil conformation adopted by the central glycosylated domain remained dominant and essentially unchanged. Surface adsorption properties as characterized by optical waveguide lightmode spectroscopy (OWLS) showed that tryptic digestion of BSM resulted in a decrease in the adsorbed mass, but pepsin digestion led to a slight increase in the adsorbed mass onto a hydrophobic surface compared to intact BSM. This is in agreement with the partial preservation of peptide segments in the terminal regions after pepsin digestion as confirmed by SEC and DLS studies. Despite a contrast in the adsorbed amount of the protease-treated BSMs onto the surface, both proteases substantially deteriorated the lubricating capabilities of BSM at a hydrophobic interface. The present study supports the notion that the terminal domains of BSM are critical to the adsorption and lubricating properties of BSM at hydrophobic interfaces. PMID- 26153255 TI - Chronic invasive fungal sinusitis associated with intranasal drug use. AB - Chronic invasive fungal sinusitis (CIFS) is a rare but potentially aggressive form of invasive fungal disease that occurs in immunocompetent patients. We report a case of CIFS in an otherwise healthy young adult associated with intranasal illicit drug abuse. The patient presented with nonhealing nasal septal and palatal perforations. Biopsy demonstrated invasive Aspergillus flavus requiring surgical debridement and extended intravenous antifungal therapy. Tissue necrosis and ulceration related to intranasal drug use should be recognized as a potential risk factor for invasive fungal sinusitis. PMID- 26153256 TI - Evaluating left ventricular systolic dysfunction: Stress echocardiography. PMID- 26153257 TI - Ischaemic vs non-ischaemic dilated cardiomyopathy: The value of nuclear cardiology techniques. PMID- 26153258 TI - How to differentiate the etiology of LV dysfunction as to whether it is "ischemic cardiomyopathy" or "dilated non-ischemic cardiomyopathy"? Invasive coronary and myocardial assessment is the approach of first choice. PMID- 26153259 TI - Debates: Introduction. PMID- 26153260 TI - Computed tomography: The optimal imaging method for differentiation of ischemic vs non-ischemic cardiomyopathy. PMID- 26153261 TI - The case for CMR. PMID- 26153262 TI - PET/CT and CMR imaging in a patient with chest pain and unobstructed coronary vessels. PMID- 26153263 TI - Imaging the patient with a new diagnosis of heart failure in the contemporary era. PMID- 26153265 TI - Strength Deterioration of Nonfractal Particle Aggregates in Simple Shear Flow. AB - The restructuring of a nonfractal particle aggregate in simple shear flow was simulated by a Stokesian dynamics approach. We studied the deformation and the resultant strength change of aggregates by the surrounding flow under the condition that the cohesive strength of an aggregate is comparable to the fluid stress. In particular, we focused on how the aggregate deteriorates because of the fluid stress exerted on it periodically. The image analysis was applied to visualized simulation results for the quantitative estimation of irreversible change in an aggregate configuration. We examined the structural change in the aggregate from various perspectives, i.e., the outer shape, the internal strength, and the fluid stress on the surface of the aggregate. The simulation results show that the aggregate gets squashed after an intricate restructuring process and it elongates along with the streamline as experimentally observed in the previous study. Regarding the internal strength, the weakest point locally develops in the aggregate by periodically varying the fluid stress. A combination of rotation and elongation effects of shear flow is complexly involved in the deterioration of the internal strength of the aggregate. PMID- 26153266 TI - Selective reinnervation for bilateral vocal cord paralysis using the superior laryngeal nerve. PMID- 26153267 TI - The symbiosis of contact force catheter use for hybrid ablation for atrial fibrillation. AB - OBJECTIVE: Reconduction across an ablation line is a common reason for arrhythmia recurrence over time. The hybrid procedure combines epicardial ablation of the pulmonary vein (PV) and creation of a box lesion with endocardial touch-ups for any electrical gaps. A high contact force (CF) between the ablation tip and cardiac tissue may increase the risk of thrombus formation, catheter tip charring, steam pop formation, and even cardiac perforation. CF monitoring is a significant new parameter for titration of the CF for creating an adequate lesion. METHODS: Thirty-eight consecutive patients underwent epicardial ablation using bipolar radiofrequency devices. After checking electrical bidirectional block of the ablation lines, an endocardial CF catheter was used for further ablation (if needed) to complete the isolation of PVs, box lesion, cavotricuspid isthmus (CTI), and complex fractionated atrial electrograms (CFAE). RESULTS: Endocardial touch-up was needed for 2 PVs (1.3 %) and 10 (26.3 %) box lesions. It was also used for the CTI line in 7 (18.4 %) patients, atrial tachycardia in 3 (7.9 %) patients, and additional CFAE ablation in 17 (44.7 %) patients. All 5 patients with arrhythmia recurrence had a mean CF < 10 g (p = 0.03). Procedure duration was significantly shorter in the CF group (223 +/- 57 vs. 256 +/- 60 min, p = 0.03) compared with control group. CONCLUSION: Use of CF catheters is safe, feasible, and complementary to a hybrid procedure setup for atrial fibrillation ablation. Its real-time monitoring may predict future arrhythmia recurrence, and decrease procedure time. PMID- 26153268 TI - Effect of injection augmentation on need for framework surgery in unilateral vocal fold paralysis. AB - OBJECTIVES/HYPOTHESIS: To determine whether injection augmentation reduces the likelihood of ultimately needing definitive framework surgery in unilateral vocal fold paralysis (UVFP) patients. STUDY DESIGN: Retrospective cohort study. METHODS: All patients diagnosed with UVFP (2008-2012) at the academic center were identified. The time from symptom onset to presentation to either community otolaryngologist and/or academic center, as well as any directed treatment(s), were recorded. Stepwise, multivariate logistic regression analysis was used to determine whether injection augmentation independently affected odds of needing definitive, framework surgery among patients who were seen within 9 months of symptom onset and had not undergone any prior rehabilitative procedures. RESULTS: Cohort consisted of 633 patients (55% female, 80% Caucasian, median age 60 years) with UVFP. The majority of etiologies were either surgery (48%) or idiopathic (37%). Duration to presentation at community otolaryngologist was shorter than to the academic center (median 2 vs. 6 months). Overall, less than half of UVFP patients had any operation (46%). Multivariate logistic regression found that earlier injection augmentation did not affect odds of ultimately undergoing framework surgery (odds ratio 1.13; confidence interval, 0.92-1.40; P = 0.23). CONCLUSION: Nearly half of UVFP patients do not require any rehabilitative procedure. When indicated, early injection augmentation is effective at temporarily alleviating associated symptoms but does not reduce likelihood of needing a definitive framework operation in patients with UVFP. Understanding practice patterns and fostering early detection and treatment may improve quality of life in this patient population. PMID- 26153269 TI - Nasolabial cysts: A systematic review of 311 cases. AB - OBJECTIVES/HYPOTHESIS: Nasolabial cysts are rare nonodontogenic cysts arising commonly in the nasal alar region. Intraoral sublabial resection of nasolabial cysts is considered the standard treatment modality. In the past 16 years, transnasal endoscopic marsupialization has emerged as an alternative approach for these lesions. A systematic review on this entity was performed to evaluate management and outcomes. DATA SOURCES: PubMed/MEDLINE Database. METHODS: A search of literature including nasolabial cysts, nasoalveolar cysts, and Klestadt's cysts was performed using the PubMed/MEDLINE database. Parameters regarding presentation, treatment, imaging, histology, and complications were extracted and subsequently analyzed. RESULTS: Seventy-nine articles with 311 patient cases were included in this analysis. In cases reporting location, nasolabial cysts occurred 46.9%, 37.5%, and 10.9% on the left, right, and bilaterally, respectively. The most common presenting complaint was facial swelling in 168 out of 237 patients (70.9%). Computed tomography was the most commonly employed imaging study (n = 170). Surgical excision of nasolabial cysts was performed using an intraoral sublabial approach in 184 patients. Seventy-nine patients underwent endoscopic transnasal marsupialization. The most common complication following surgical treatment of nasolabial cysts was postoperative facial/perinasal swelling. Three and two recurrences were reported in the sublabial excision group and transnasal marsupialization group, respectively. Mean follow-up time was 20.0 months. CONCLUSIONS: Endoscopic transnasal marsupialization is a relatively new alternative to intraoral sublabial resection of nasolabial cysts, with similar efficacy. The rates of postoperative swelling, pain, and recurrence are similar in both groups. PMID- 26153270 TI - Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood Onset Type 1 Diabetes. AB - OBJECTIVE: The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: During 2010-2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 +/- 7 and 41 +/ 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 +/- 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986 1988. Cognitive impairment status was based on the number of test scores >=1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS: The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6-0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3-0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index >=1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS: Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI, deserve further study. PMID- 26153271 TI - Allogeneic Mesenchymal Precursor Cells in Type 2 Diabetes: A Randomized, Placebo Controlled, Dose-Escalation Safety and Tolerability Pilot Study. AB - OBJECTIVE: To assess the safety, tolerability, and feasibility of adult allogeneic bone marrow-derived mesenchymal precursor cells (MPCs) in type 2 diabetes inadequately controlled with metformin either alone or with one additional oral antidiabetic agent. RESEARCH DESIGN AND METHODS: The study was a dose-escalating randomized placebo-controlled trial assessing one intravenous (IV) infusion of MPCs (rexlemestrocel-L; Mesoblast Inc.) 0.3 * 10(6)/kg (n = 15), 1.0 * 10(6)/kg (n = 15), or 2.0 * 10(6)/kg (n = 15) or placebo (n = 16). Study duration was 12 weeks. RESULTS: Subjects (21 women, 40 men) with a mean +/- SD baseline HbA1c 8.3 +/- 1.0% (67 +/- 10.9 mmol/mol), BMI 33.5 +/- 5.5 kg/m(2), and diabetes duration 10.1 +/- 6.0 years were enrolled at 18 U.S. sites. No acute adverse events (AEs) were associated with infusion. No serious AEs, serious hypoglycemia AEs, or discontinuations due to AEs over 12 weeks were found. No subjects developed donor-specific anti-HLA antibodies or became sensitized. The safety profile was comparable among treatment groups. Compared with placebo, a single IV infusion of rexlemestrocel-L reduced HbA1c at all time points after week 1. The adjusted least squares mean +/- SE dose-related differences in HbA1c from placebo in the rexlemestrocel-L groups ranged from -0.1 +/- 0.2% (-1.1 +/- 2.2 mmol/mol) to -0.4 +/- 0.2% (4.4 +/- 2.2 mmol/mol) at 8 weeks and from 0.0 +/- 0.25% to -0.3 +/- 0.25% (-3.3 +/- -2.7 mmol/mol) at 12 weeks (P < 0.05 for 2.0 * 10(6)/kg dose at 8 weeks). The clinical target HbA1c <7% (53 mmol/mol) was achieved by 33% (5 of 15) of the subjects who received the 2.0 * 10(6)/kg dose vs. 0% of those who received placebo (P < 0.05). CONCLUSIONS: This short-term study demonstrates the safety and feasibility of up to 246 million MPCs in subjects with type 2 diabetes. PMID- 26153272 TI - The Role of Markers of Low-Grade Inflammation for the Early Time Course of Glycemic Control, Glucose Disappearance Rate, and beta-Cell Function in Recently Diagnosed Type 1 and Type 2 Diabetes. AB - OBJECTIVE: Inflammatory processes are involved in the progression of insulin resistance and beta-cell dysfunction in individuals with prediabetes and contribute to the development of diabetes. We hypothesized that higher levels of biomarkers of low-grade inflammation are associated with the early progression of recently diagnosed diabetes. RESEARCH DESIGN AND METHODS: Within the prospective German Diabetes Study, patients with recently diagnosed type 1 (n = 42) and type 2 (n = 94) diabetes underwent detailed metabolic characterization within the first year after diagnosis and 2 years thereafter. Associations between changes in markers of low-grade inflammation with changes in glycemic control, beta-cell function, and glucose disappearance rate were assessed using multivariable linear regression analysis. Associations were adjusted for age, sex, BMI, smoking status, and 2-year changes in BMI, smoking status, and glucose-lowering medication. RESULTS: Patients with type 1 and type 2 diabetes exhibited good glucometabolic control at baseline (mean HbA1c 7.08 +/- 1.58% [54 +/- 17 mmol/mol] and 6.43 +/- 0.98% [47 +/- 11 mmol/mol], respectively) and 2 years thereafter (mean HbA1c 7.03 +/- 1.20% [53 +/- 13 mmol/mol] and 6.62 +/- 1.14% [49 +/- 13], respectively). Two-year increases of high-sensitivity C-reactive protein, soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 in type 2 diabetes and of IL-18 in type 1 diabetes were associated with 2-year increases of HbA1c. Additionally, 2-year increases of sE-selectin were associated with 2-year decreases of prehepatic beta-cell function in type 2 diabetes (all P < 0.05). CONCLUSIONS: These data indicate that with the clinical onset of diabetes, low-grade inflammation relates to worsening of glycemia and that endothelial activation may contribute to decreasing beta-cell function. PMID- 26153273 TI - Inhaled Formoterol Diminishes Insulin-Induced Hypoglycemia in Type 1 Diabetes. AB - OBJECTIVE: Hypoglycemia is one of the major factors limiting implementation of tight glycemic control in patients with type 1 diabetes and is associated with increased morbidity and mortality during intensive insulin treatment. beta-2 Adrenergic receptor (AR) agonists have been reported to diminish nocturnal hypoglycemia; however, whether long-acting inhaled beta-2 AR agonists could potentially be used to treat or prevent hypoglycemia has not been established. RESEARCH DESIGN AND METHODS: Seven patients with type 1 diabetes and seven healthy control subjects received inhaled formoterol (48 MUg), a highly specific beta-2 AR agonist, or a placebo during a hyperinsulinemic-hypoglycemic clamp study to evaluate its capacity to antagonize the effect of insulin. In a second set of studies, five subjects with type 1 diabetes received inhaled formoterol to assess its effect as a preventive therapy for insulin-induced hypoglycemia. RESULTS: During a hyperinsulinemic-hypoglycemic clamp, compared with placebo, inhaled formoterol decreased the glucose infusion rate required to maintain plasma glucose at a target level by 45-50% (P < 0.05). There was no significant effect on glucagon, epinephrine, cortisol, or growth hormone release (P = NS). Furthermore, in volunteers with type 1 diabetes 1 h after increasing basal insulin delivery twofold, glucose levels dropped to 58 +/- 5 mg/dL, whereas hypoglycemia was prevented by inhaled formoterol (P < 0.001). CONCLUSIONS: Inhalation of the beta-2 AR-specific agonist formoterol may be useful in the prevention or treatment of acute hypoglycemia and thus may help patients with type 1 diabetes achieve optimal glucose control more safely. PMID- 26153274 TI - Influence of ABCB1 Genotype in Collies on the Pharmacokinetics and Pharmacodynamics of Loperamide in a Dose-Escalation Study. AB - Thirty-three Collies (14 male and 19 female) were used in a dose-escalation study to determine the impact of ABCB1 genotype on loperamide pharmacokinetics (PK) and pharmacodynamics (PD). Loperamide was orally administered in four ascending doses (0.01, 0.05, 0.1, or 0.2 mg/kg) over a 4-wk period to fasted Collies. Comparisons were made within each dose to genotype, phenotype, and whether Collies received three (3D) or four (4D) loperamide doses. The 3D and 4D groupings had statistically significant differences in systemic drug exposure (defined by the area under the concentration-versus-time profile estimated from time zero to the last quantifiable drug concentration, AUC0-last). In contrast, statistical differences in AUC0-last only occurred in the comparison between wild-type (WT) Collies versus homozygous mutant (Mut) Collies administered 0.1 mg/kg. Statistical differences in the proportionality relationship were observed when comparing 3D to 4D Collies, and the WT to Mut Collies. Intersubject variability in drug exposure tended to be twice as high between Mut and WT Collies. Associations were observed between systemic drug exposure and ataxia or depression but not between systemic drug exposure and mydriasis or salivation. Thus, Collies expressing the greatest sensitivity to CNS-associated effects of loperamide (Mut) tended to have higher drug exposure compared with those less sensitive to the adverse effects of loperamide. Genotype and phenotype only partially explained differences in loperamide PK and PD, suggesting this relationship may not be straightforward and that other factors need to be considered. Accordingly, the PD and PK of one P-glycoprotein substrate only partially predicted the likelihood of adverse responses to unrelated substrates. PMID- 26153275 TI - Cross-Species Differences in the Preclinical Pharmacokinetics of CT7758, an alpha4beta1/alpha4beta7 Integrin Antagonist. AB - CT7758, a carboxylate containing alpha4beta1/alpha4/beta7 integrin antagonist, was characterized for its pharmacokinetic profile in various in vitro and in vivo assays in support of clinical development. The oral bioavailability of CT7758 was 4% in mice, 2% in rats, 7-55% in dogs, and 0.2% in cynomolgus monkeys. The low bioavailability in rodents and monkey results from low intestinal absorption as evidenced by a low fraction absorbed in the rat portal vein model (3%), low-to medium permeability in Caco-2 cells (<=1.3 * 10(-6) cm/s) with evidences of polarized efflux, and high polar surface area (104 A). In rodents and cynomolgus monkeys, the total plasma clearance was moderate to high (>=50% hepatic blood flow QH) and associated with a short elimination half-life (<=1 hour). This contrast with the dog data which showed a much lower clearance (6% QH) and a longer t1/2 (2.4 hours). The volume of distribution (Vz) also varied significantly across species with value of 5.5, 2.8, 0.24, and 0.93 l/kg in mouse, rat, dog, and cynomolgus monkey, respectively. In vitro assays demonstrated that active hepatic uptake accounted for most of the in vivo clearance and was the source of the large species variability. In vitro uptake assays predicted a total plasma clearance in humans in the low range (33% QH), a finding subsequently confirmed in the clinic. Assays in OAPT1B1-transfected cells demonstrated active uptake transport through this transporter. The prospect of limited absorption in human prompted the synthesis an ethyl ester prodrug, CDP323, which demonstrated higher in vitro permeability, increased oral bioavailability, as well as efficient in vivo release of its active moiety CT7758. PMID- 26153276 TI - Synthesis and enhanced electrochemical catalytic performance of monolayer WS2(1 x) Se2x with a tunable band gap. AB - The first realization of a tunable band-gap in monolayer WS2(1-x) Se2x is demonstrated. The tuning of the bandgap exhibits a strong dependence of S and Se content, as proven by PL spectroscopy. Because of its remarkable electronic structure, monolayer WS2(1-x) Se2x exhibits novel electrochemical catalytic activity and offers long-term electrocatalytic stability for the hydrogen evolution reaction. PMID- 26153277 TI - Some promising news about psychosocial interventions for adolescent self-harm. PMID- 26153278 TI - Mycobacterial spindle cell pseudotumour of the brain in a patient with sarcoidosis. AB - Mycobacterial spindle cell pseudotumours (MSP) are benign lesions characterised by local proliferation of spindle-shaped histiocytes caused by mycobacterial infections. Cerebral MSP due to Mycobacterium avium intracellulare (MAI) infection is rare, and is often misdiagnosed clinically and radiologically as a brain tumour. We present a case with underlying sarcoidosis and known pulmonary MAI infection presenting with partial seizures and headaches. Imaging of the brain revealed a solitary extra axial tumour within the right temporal area. Biopsy of the tumour showed evidence of MPS due to MAI infection. Prolonged treatment with antituberculous therapy showed complete resolution of the cerebral lesion. PMID- 26153279 TI - Protrusio acetabuli: a rare cause of pulmonary embolus. AB - Protrusio acetabuli is an uncommon complication of total hip arthroplasty, which results in intrapelvic implant migration after erosion of medial acetabular wall. We present a case of severe prosthetic migration with the formation of haematoma and impingement on iliac vessels leading to thrombosis and subsequent pulmonary embolus. This is the first reported case of protrusio acetabuli as a cause of pulmonary embolus. PMID- 26153280 TI - Late and multifocal presentations of malignant peripheral nerve sheath tumours following radiotherapy. AB - Peripheral nerve sheath tumours are a well-recognised complication of radiotherapy. Single tumours presenting up to 10 years after initial treatment have been previously described. We report an individual with two anatomically separate nerve sheath tumours developing at different time intervals following initial treatment, after 38 and 42 years, respectively. This case illustrates the importance of maintaining vigilance for the development of complications even at an advanced stage following index radiotherapy treatment. PMID- 26153281 TI - Immunosuppression and a serious opportunistic infection: an unfortunate price to pay. AB - A 57-year-old woman with diabetes mellitus type 1, status postcadaveric pancreas transplant alone 11 years ago, on chronic immunosuppression, and dialysis dependent end-stage renal disease, presented with 2 months of progressive generalised weakness, lumbar back pain with right lower extremity radiculopathy and episodic symptomatic hypotension. Preliminary infectious disease work up was unremarkable. She was discharged following symptomatic improvement. She represented 3 days later with continued functional decline and leucocytosis. Chest X-ray demonstrated diffuse pulmonary nodules, confirmed on chest CT scan. CT-guided biopsy of a right upper lobe nodule was performed; studies confirmed Nocardia farcinica. Further imaging revealed bilateral white matter intracranial lesions, and extensive Nocardia-positive fluid collections in the right gluteal and vastus musculature, requiring periodic surgical debridement. She was treated with multiple antimicrobials, including trimethoprim-sulfamethoxazole, amoxicillin/clavulanate and moxifloxacin. She was discharged after a 6-month hospitalisation. PMID- 26153282 TI - Treatment resistant somatic delusions in bipolar disorder. AB - Two patients each developed a single, fixed somatic delusion complicating their existing bipolar disorder. Both failed to respond to a range of antidepressant and antipsychotic medications. They each showed a partial response to clozapine and to electroconvulsive therapy, with resolution of mood symptoms and diminution of their ongoing somatic preoccupation. A review of case reports suggests a possible relationship between somatic delusions and affective disorders. PMID- 26153283 TI - Novel use of 4D-CTA in imaging of intranidal aneurysms in an acutely ruptured arteriovenous malformation: is this the way forward? AB - Ruptured arteriovenous malformation (AVM) is a frequent cause of intracranial hemorrhage. The presence of associated aneurysms, especially intranidal aneurysms, is considered to increase the risk of re-hemorrhage. We present two cases where an intranidal aneurysm was demonstrated on four-dimensional CT angiography (time-resolved CT angiography) (4D-CTA). These features were confirmed by digital subtraction angiography (catheter arterial angiogram). This is the first report of an intranidal aneurysm demonstrated by 4D-CTA. 4D-CTA can offer a comprehensive evaluation of the angioarchitecture and flow dynamics of an AVM for appropriate classification and management. PMID- 26153284 TI - Intussusception in an adult with cystic fibrosis successfully reduced with contrast enema. PMID- 26153285 TI - Perinatal management of fetal supraventricular tachycardia complicated by maternal pertussis. AB - Prenatal pertussis has become a concern once again with the reappearance of the disease in the USA. A 30-year-old mother whose pregnancy was complicated with fetal arrhythmia was referred for further evaluation in the third trimester. After initial treatment with antiarrhythmic medications due to continued irregular rhythm, she was revisited for persistent hacking cough at 38 weeks gestational age. PCR examination confirmed pertussis diagnosis. Owing to increased risk of digoxin toxicity with concurrent antibiotic administration, antiarrhythmic medication was discontinued. Delivery was induced 2 days after the initiation of azithromycin therapy to prevent the transmission of the disease to the neonate. A well-planned delivery in a patient with prenatal diagnosis prevents neonatal infection while considering the obstetrical dilemma for concurrent management of the intrauterine arrhythmia and antibiotic administration. PMID- 26153286 TI - Novel use of videolaryngoscopy to remove a foreign body. AB - We present a case where a C-MAC video laryngoscope was used to remove a duodenal stent that was inadvertently dislodged in the patient's proximal oesophagus during an interventional radiology procedure, causing upper airway obstruction. Using the C-MAC and a pair of Magill forceps, we were able to successfully remove the stent. Video feed allowed for further communication between us and the ENT (ear, nose and throat) surgeons. PMID- 26153287 TI - Liver perforation following foreign body ingestion: an important clinical lesson. AB - A 25-year-old woman presented to the surgical unit with a 1-week history of ingestion of a pen. Examination revealed a minimally tender epigastrium with no peritonism. Investigations were unremarkable, with normal bloods and no free air on erect chest radiograph. At the time of endoscopy, the pen appeared to have perforated the lesser curve of the stomach. Endoscopic extraction was abandoned and a CT arranged, revealing the tip of the pen lying within the left lobe of the liver. The pen was removed at laparotomy with an uneventful recovery. This case highlights the importance of considering the potential for injury to other structures following gastric perforation, and the importance of having a low threshold for further imaging. PMID- 26153288 TI - Acute haemorrhage secondary to arteriovenous haemodialysis fistula pseudoaneurysm -the challenge of restoring a deformed upper limb. PMID- 26153289 TI - Pacemaker lead-associated thrombosis in cardiac resynchronisation therapy. AB - Pacemaker lead-associated thrombosis is a possible complication of any cardiac implantable electronic device. We present a case of a middle-aged woman with a history of ischaemic left ventricular failure, who presented with fever and other non-specific symptoms 4 months after cardiac resynchronisation therapy. A transoesophageal echocardiogram confirmed a vegetation-like structure originating from the pacemaker lead in the right atrium. The patient was treated with intravenous antibiotics followed by open heart surgery in order to remove this mass as well as the pacing device, including all three pacing leads. Histology and culture of the retrieved mass confirmed a sterile thrombus with no features to suggest an infected mass (vegetation). The patient made an uncomplicated recovery and there were no long-term sequelae on follow-up during the 2 years after the event. PMID- 26153290 TI - Prostatic adenocarcinoma presenting as isolated inguinal lymphadenopathy. AB - Prostatic adenocarcinoma (CaP) is the most common cancer in males and approximately 50% of patients have metastases at presentation, most commonly spreading to the bones and regional lymph nodes. CaP metastasising to inguinal lymph nodes in the absence of pelvic lymphadenopathy or other metastases is very uncommon. A 66-year-old man presented with isolated left inguinal lymphadenopathy of 3 months duration and a history of lower urinary tract symptoms for 1 year. He had prostatic cancer extending into the bladder base and seminal vesicles on contrast-enhanced CT of the pelvis, and asymptomatic vertebral secondaries on skeletal scintigraphy. Transrectal ultrasound biopsy revealed adenocarcinoma (Gleason score 3+4=7), and inguinal lymph node biopsy showed metastatic adenocarcinoma positive for prostate-specific antigen (PSA). As inguinal lymphadenopathy may also be due to other causes, biopsy is useful and meticulous clinical examination is a must in these patients. PMID- 26153291 TI - Aborted sudden cardiac death associated with an anomalous right coronary artery. AB - Coronary artery anomalies arising from the opposite sinus of Valsalva and having an interarterial course between the aorta (AO) and pulmonary artery (PA) are the second most common cause of sudden cardiac death among young athletes, after hypertrophic cardiomyopathy. The right coronary artery (RCA) originating from the AO above the left sinus of Valsalva (LSV) is an extremely rare anomaly. We report the first case of a RCA arising from the AO above the LSV that subsequently runs between the AO and the PA, discovered by a 64-slice multidetector coronary CT, in a patient who was successfully resuscitated from ventricular fibrillation (VF) cardiac arrest while running in a marathon race. PMID- 26153292 TI - Late neonatal presentation of reduced arm movement due to painful infective lymphadenopathy. AB - We report two cases of 21-day-old male infants, Baloo and Bagheera, both admitted with unilateral reduced arm movement secondary to painful lymphadenopathy, which is a presentation previously unreported in the paediatric literature. The only abnormal finding following investigations in both neonates was infective lymphadenopathy; we hypothesise that the inflamed lymph nodes were tender when the surrounding muscles, fascia or skin were moved, so that the infants learnt to reduce arm movement to minimise pain. This report explores the differential diagnoses for reduced arm movement in neonates, and highlights the importance of sepsis with painful lymphadenopathy as a differential diagnosis in neonates presenting with reduced arm movement. PMID- 26153293 TI - Calcified meconium pseudocyst: X-ray diagnosis of meconium peritonitis at birth. PMID- 26153294 TI - Isolated hepatosplenic tuberculosis: a rare presentation. AB - Tuberculosis caused by Mycobacterium tuberculosis presents a major health challenge in endemic countries and spares no organ in the human body. This infection is a mimicker of various disease processes such as metastasis, lymphoproliferative diseases, and other granulomatous conditions such as sarcoidosis and fungal infections. The most challenging and important differential is metastasis, especially in the disseminated form of tuberculosis. We present a histopathologically proven case of isolated hepatosplenic tuberculosis that was provisionally diagnosed as lymphoma due to its unusual, restricted involvement of the liver and spleen. PMID- 26153295 TI - Ipilimumab-associated colitis or refractory Clostridium difficile infection? AB - We present a case of a patient with a diagnostic dilemma who was referred for possible faecal microbiota transplantation (FMT) for refractory diarrhoea secondary to Clostridium difficile infection (CDI). On detailed history, the patient was exposed to ipilimumab concomitantly while being treated for CDI, and was instead diagnosed with diarrhoea secondary to superimposed ipilimumab associated colitis. Ipilimumab is an anti-CTLA4 monoclonal antibody approved for use in metastatic melanoma and under trial for other indications. Ipilimumab is associated with several immune-related adverse effects, of which diarrhoea and colitis are the most common. While FMT has shown tremendous efficacy in managing recurrent and refractory CDI, it was not offered in this case due to negative C. difficile testing showing a high degree of suspicion for ipilimumab-associated colitis due to recent drug use. Our patient was successfully managed with fluid resuscitation and steroids, and remains symptom free at last follow-up at 9 months. PMID- 26153296 TI - Pulmonary aspergillosis presenting with recurrent haemoptysis. AB - Pulmonary aspergillosis presents with a variety of clinical forms including invasive pulmonary aspergillosis, chronic necrotising aspergillosis, aspergilloma, chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Haemoptysis is a devastating complication of pulmonary aspergillosis and a common indication for surgery. We report a case of a 54-year-old man with a history of pulmonary tuberculosis and diabetes mellitus, who presented with productive cough and haemoptysis for 2 months. Chest CT revealed a 30 mm diameter soft tissue mass in the upper lobe of the right lung. Haemoptysis subsided with conservative measures, but 2 weeks later the patient developed a new episode of persistent haemoptysis, which was only partially controlled with bronchial arterial embolisation. He underwent right upper and middle lobectomy. Histology examination confirmed the presence of a fungal cavitary lesion. The patient was started on voriconazole, and recovered with no recurrence at 18 months follow-up. PMID- 26153297 TI - Interaction of Fibrin with the Very Low Density Lipoprotein Receptor: Further Characterization and Localization of the Fibrin-Binding Site. AB - Our recent study revealed that fibrin interacts with the very low density lipoprotein receptor (VLDLR) on endothelial cells through its betaN domains, and this interaction promotes transendothelial migration of leukocytes and thereby inflammation. The major aims of this study were to further characterize this interaction and localize the fibrin-binding site in the VLDLR. To localize the fibrin-binding site, we expressed a soluble extracellular portion of this receptor, sVLDLRHT, its N- and C-terminal regions, VLDLR(1-8)HT and des(1 8)VLDLRHT, respectively, and a number of VLDLR fragments containing various combinations of CR domains and confirmed their proper folding by fluorescence spectroscopy. Interaction of these fragments with the (beta15-66)2 fragment corresponding to a pair of VLDLR-binding betaN domains of fibrin was tested by different methods. Our experiments performed by an enzyme-linked immunosorbent assay and surface plasmon resonance revealed that the VLDLR(1-8)HT fragment containing eight CR domains of VLDLR and its subfragments, VLDLR(1-4)HT and VLDLR(2-4)HT, interact with (beta15-66)2 with practically the same affinity as sVLDLRHT while the affinity of VLDLR(2-3)HT was ~2-fold lower. In contrast, des(1 8)VLDLRHT exhibited no binding. Formation of the complex in solution between the fibrin-binding fragments of VLDLR and (beta15-66)2 was detected by fluorescence spectroscopy. In addition, formation of a complex between VLDLR(2-4)HT and (beta15-66)2 in solution was confirmed by size-exclusion chromatography. Thus, the results obtained indicate that minimal fibrin-binding structures are located within the second and third CR domains of the VLDL receptor and the presence of the fourth CR domain is required for high-affinity binding. They also indicate that tryptophan residues of CR domains are involved in this binding. PMID- 26153298 TI - Binding Rate Constants Reveal Distinct Features of Disordered Protein Domains. AB - Intrinsically disordered proteins (IDPs) are abundant in the proteome and involved in key cellular functions. However, experimental data about the binding kinetics of IDPs as a function of different environmental conditions are scarce. We have performed an extensive characterization of the ionic strength dependence of the interaction between the molten globular nuclear co-activator binding domain (NCBD) of CREB binding protein and five different protein ligands, including the intrinsically disordered activation domain of p160 transcriptional co-activators (SRC1, TIF2, ACTR), the p53 transactivation domain, and the folded pointed domain (PNT) of transcription factor ETS-2. Direct comparisons of the binding rate constants under identical conditions show that the association rate constant, kon, for interactions between NCBD and disordered protein domains is high at low salt concentrations (90-350 * 10(6) M(-1) s(-1) at 4 degrees C) but is reduced significantly (10-30-fold) with an increasing ionic strength and reaches a plateau around physiological ionic strength. In contrast, the kon for the interaction between NCBD and the folded PNT domain is only 7 * 10(6) M(-1) s( 1) (4 degrees C and low salt) and displays weak ionic strength dependence, which could reflect a distinctly different association that relies less on electrostatic interactions. Furthermore, the basal rate constant (in the absence of electrostatic interactions) is high for the NCBD interactions, exceeding those typically observed for folded proteins. One likely interpretation is that disordered proteins have a large number of possible collisions leading to a productive on-pathway encounter complex, while folded proteins are more restricted in terms of orientation. Our results highlight the importance of electrostatic interactions in binding involving IDPs and emphasize the significance of including ionic strength as a factor in studies that compare the binding properties of IDPs to those of ordered proteins. PMID- 26153299 TI - Chemoselective, Stereospecific, and Living Polymerization of Polar Divinyl Monomers by Chiral Zirconocenium Catalysts. AB - This contribution reports the first chemoselective, stereospecific, and living polymerization of polar divinyl monomers, enabled by chiral ansa-zirconocenium catalysts through an enantiomorphic-site controlled coordination-addition polymerization mechanism. Silyl-bridged-ansa-zirconocenium ester enolate 2 has been synthesized and structurally characterized, but it exhibits low to negligible activity and stereospecificity in the polymerization of polar divinyl monomers including vinyl methacrylate (VMA), allyl methacrylate (AMA), 4 vinylbenzyl methacrylate (VBMA), and N,N-diallyl acrylamide (DAA). In contrast, ethylene-bridged-ansa-zirconocenium ester enolate 1 is highly active and stereospecific in the polymerization of such monomers including AMA, VBMA, and DAA. The polymerization by 1 is perfectly chemoselective for all four polar divinyl monomers, proceeding exclusively through conjugate addition across the methacrylic C?C bond, while leaving the pendant C?C bonds intact. The polymerization of DAA is most stereospecific and controlled, producing essentially stereoperfect isotactic PDAA with [mmmm] > 99%, M(n) matching the theoretical value (thus a quantitative initiation efficiency), and a narrow molecular weight distribution (D = 1.06-1.16). The stereospecificity is slightly lower for the AMA polymerization but still leading to highly isotactic poly(allyl methacrylate) (PAMA) with 95-97% [mm]. The polymerization of VBMA is further less stereospecific, affording PVBMA with 90-94% [mm], while the polymerization VMA is least stereospecific. Several lines of evidence from both homo- and block copolymerization results have demonstrated living characteristics of the AMA polymerization by 1. Mechanistic studies of this polymerization have yielded a monometallic coordination-addition polymerization mechanism involving the eight membered chelating intermediate. Post-functionalization of isotactic polymers bearing the pendant vinyl group on every repeating unit via the thiol-ene "click" reaction achieves a full conversion of all the pendant double bonds to the corresponding thioether bonds. Photocuring of such isotactic polymers is also successful, producing an elastic material readily characterizable by dynamic mechanical analysis. PMID- 26153300 TI - Medicaid's Growing Role In Care Delivery. PMID- 26153301 TI - Once A Welfare Add-On, Medicaid Takes Charge In Reinventing Care. AB - States around the country have seized on Medicaid as a force for health system transformation. PMID- 26153302 TI - Medicaid At 50: Remarkable Growth Fueled By Unexpected Politics. AB - Medicaid has grown exponentially since the mid-1980s, during both conservative Republican and liberal Democratic administrations. How has this happened? The answer is rooted in three political variables: interest groups, political culture, and American federalism. First, interest-group support (from hospitals, nursing homes, and insurers) is more influential than the fragmented group opposition (from underpaid office-based physicians). Second, Medicaid provides a partial counterweight to conservative charges of a federal health care takeover because of the states' roles in administering the program. Third, Medicaid's intergovernmental fiscal partnership creates financial incentives for state and federal officials to expand enrollment-expansions that these policy makers often favor, given the program's increasingly important role in the nation's health care system. This institutional dynamic is here called catalytic federalism. PMID- 26153303 TI - Community Health Centers And Medicaid At 50: An Enduring Relationship Essential For Health System Transformation. AB - Community health centers reach their fiftieth anniversary in 2015, along with Medicaid. Health policy makers have understood the programs' symbiotic connection from the earliest days of their implementation. Medicaid's expansion and growth have made the modern community health center program possible, while health centers represent one of the principal sources of primary care for the nation's Medicaid population. With their shared mission and high level of interdependence, Medicaid and community health centers are essential for continued health system transformation in medically underserved communities nationwide--for example, by implementing delivery system reforms aimed at increasing clinical integration and improving efficiencies and by becoming medical homes for high-risk patients. Achieving this transformation will depend on the ability of community health centers and Medicaid to understand and respond to the challenges that each faces, while fully deploying the strengths that each has to offer. PMID- 26153304 TI - Many Medicaid Beneficiaries Receive Care Consistent With Attributes Of Patient Centered Medical Homes. AB - The patient-centered medical home (PCMH) is being embraced as a way to improve access to and quality of care and to control health care costs. However, it is not known what proportion of the Medicaid population receives care from practices that incorporate PCMH goals. Nationally representative data for 2008-12 indicate that the majority of Medicaid beneficiaries with no other coverage who reported having a usual source of care described it as consistent with at least three of five key PCMH attributes: serving multiple health needs, ease of phone contact, extended office hours, coordination of prescriptions, and shared decision making. Younger, healthier, and higher-income Medicaid beneficiaries tended to report care sources with multiple attributes, compared to the older, sicker, and lower income beneficiaries, who may be more likely to benefit from access to such care. Most attributes were associated with higher perceived quality of care and greater access, although the findings regarding health care expenditures were inconclusive. Challenges to widespread adoption of PCMH principles in Medicaid programs include targeting delivery of care consistent with those principles to high-need, high-cost populations and ensuring an adequate supply of usual sources of primary care. PMID- 26153305 TI - In California, Primary Care Continuity Was Associated With Reduced Emergency Department Use And Fewer Hospitalizations. AB - The expansion of health insurance to millions of Americans through the Affordable Care Act has given rise to concerns about increased use of emergency department (ED) and hospital services by previously uninsured populations. Prior research has demonstrated that continuity with a regular source of primary care is associated with lower use of these services and with greater patient satisfaction. We assessed the impact of a policy to increase patients' adherence to an individual primary care provider or clinic on subsequent use of ED and hospital services in a California coverage program for previously uninsured adults called the Health Care Coverage Initiative. We found that the policy was associated with a 42 percent greater probability of adhering to primary care providers. Furthermore, patients who were always adherent had a higher probability of having no ED visits (change in probability: 2.1 percent) and no hospitalizations (change in probability: 1.7 percent), compared to those who were never adherent. Adherence to a primary care provider can reduce the use of costly care because it allows patients' care needs to be managed within the less costly primary care setting. PMID- 26153306 TI - MetroHealth Care Plus: Effects Of A Prepared Safety Net On Quality Of Care In A Medicaid Expansion Population. AB - Studies of Medicaid expansion have produced conflicting results about whether the expansion is having a positive impact on health and the cost and efficiency of care delivery. To explore the issue further, we examined MetroHealth Care Plus, a Centers for Medicare and Medicaid Services (CMS) waiver program in Ohio composed of three safety-net organizations that enrolled 28,295 uninsured poor patients in closed-panel care during 2013. All participating organizations used electronic health records and patient-centered medical homes, publicly reported performance in a regional health improvement collaborative, and accepted a budget-neutral cap approved by CMS. We compared changes between 2012 and 2013 in achieving quality standards for diabetes and hypertension among 3,437 MetroHealth Care Plus enrollees to changes among 1,150 patients with the same conditions who remained uninsured in both years. Compared to continuously uninsured patients with diabetes, MetroHealth Care Plus enrollees with diabetes improved significantly more on composite standards of care and intermediate outcomes. Among enrollees with hypertension, blood pressure control improvements were insignificantly larger than those in the continuously uninsured group with hypertension. Across all 28,295 enrollees, 2013 total costs of care were 28.7 percent below the budget cap, providing cause for optimism that a prepared safety net can meet the challenges of Medicaid expansion. PMID- 26153307 TI - Lessons From Medicaid's Divergent Paths On Mental Health And Addiction Services. AB - Over the past fifty years Medicaid has taken divergent paths in financing mental health and addiction treatment. In mental health, Medicaid became the dominant source of funding and had a profound impact on the organization and delivery of services. But it played a much more modest role in addiction treatment. This is poised to change, as the Affordable Care Act is expected to dramatically expand Medicaid's role in financing addiction services. In this article we consider the different paths these two treatment systems have taken since 1965 and identify strategic lessons that the addiction treatment system might take from mental health's experience under Medicaid. These lessons include leveraging optional coverage categories to tailor Medicaid to the unique needs of the addiction treatment system, providing incentives to addiction treatment programs to create and deliver high-quality alternatives to inpatient treatment, and using targeted Medicaid licensure standards to increase the quality of addiction services. PMID- 26153308 TI - Deficiencies In Care At Nursing Homes And Racial/Ethnic Disparities Across Homes Fell, 2006-11. AB - Despite the increased use of nursing homes by minority residents, nursing home care remains highly segregated. Compared to whites, racial/ethnic minorities tend to be cared for in facilities with limited clinical and financial resources, low nurse staffing levels, and a relatively high number of care deficiency citations. We assessed the trends from 2006 to 2011 in those citations and in disparities across facilities with four different concentrations of racial/ethnic minority residents. We found that the number of health care-related deficiencies and the percentage of facilities with serious deficiencies decreased over time for all four facility groups. From 2006 to 2011 the average annual number of health care related deficiencies declined from 7.4 to 6.8 for facilities with low minority concentrations (<5 percent) and from 10.6 to 9.4 for facilities with high minority concentrations (>=35 percent). In multivariable analyses, across-site disparities in health care-related deficiencies and in life-safety deficiencies narrowed over time. We also found that increasing the Medicaid payment rate might help improve both overall quality and disparities, but state case-mix payment approaches might worsen both. These results suggest the need to reevaluate quality improvement and cost containment efforts to better foster the quality and equity of nursing home care. PMID- 26153309 TI - Federally Qualified Health Center Use Among Dual Eligibles: Rates Of Hospitalizations And Emergency Department Visits. AB - People who are eligible for both Medicare and Medicaid, known as "dual eligibles," disproportionately are members of racial or ethnic minority groups. They face barriers accessing primary care, which in turn increase the risk of potentially preventable hospitalizations and emergency department (ED) visits for ambulatory care-sensitive conditions. Federally qualified health centers provide services known to address barriers to primary care. We analyzed 2008-10 Medicare data for elderly and nonelderly disabled dual eligibles residing in Primary Care Service Areas with nearby federally qualified health centers. Among our findings: There were fewer hospitalizations for ambulatory care-sensitive conditions among blacks and Hispanics who used these health centers than among their counterparts who did not use them (16 percent and 13 percent fewer, respectively). Use of the health centers was also associated with 3 percent and 12 percent fewer hospitalizations for ambulatory care-sensitive conditions among nonelderly disabled blacks and Hispanics, respectively. These findings suggest that federally qualified health centers can reduce disparities in preventable hospitalizations for some dual eligibles. However, further efforts are needed to reduce preventable ED visits among dual eligibles receiving care in the health centers. PMID- 26153310 TI - The Supreme Court Ruling That Blocked Providers From Seeking Higher Medicaid Payments Also Undercut The Entire Program. AB - In Armstrong v. Exceptional Child Center, Inc., the US Supreme Court revisited the question of whether Medicaid providers may seek relief in federal courts when states fail to pay "sufficient" Medicaid rates. A divided Supreme Court held that the Supremacy Clause of the US Constitution does not support such actions, even when states violate the Medicaid Act of 1965. Payment sufficiency is vital to Medicaid's success in expanding health insurance coverage under the Affordable Care Act. By terminating providers' ability to seek relief in federal courts, Armstrong makes it easier for states to cut Medicaid payment rates at the same time that millions of new enrollees will enter the program, undercutting operation of the Medicaid program and its role in health care reform. PMID- 26153311 TI - An Examination Of Medicaid Delivery System Reform Incentive Payment Initiatives Under Way In Six States. AB - Medicaid waivers for Delivery System Reform Incentive Payment (DSRIP) seek to hold hospitals and other providers accountable for measureable improvements in health care delivery. We explore the policy context giving rise to these waivers in six states, with particular attention to the interplay among the financial needs of hospitals; the rise of managed care; and federal interest in replacing an "unconditional" Medicaid funding stream, the upper payment limit, with one rooted in pay-for-performance. Key characteristics of these main DSRIP waivers are compared with a particular focus on the establishment of project menus, performance metrics, and pay-for-performance processes. Concluding sections discuss the potential and limits of the waivers as vehicles for health care reform. The long-term durability and impact of DSRIP remains unclear. But federal and state officials have made considerable headway in planning and otherwise laying the groundwork for it. PMID- 26153312 TI - Early Medicaid Expansion In Connecticut Stemmed The Growth In Hospital Uncompensated Care. AB - As states continue to debate whether or not to expand Medicaid under the Affordable Care Act (ACA), a key consideration is the impact of expansion on the financial position of hospitals, including their burden of uncompensated care. Conclusive evidence from coverage expansions that occurred in 2014 is several years away. In the meantime, we analyzed the experience of hospitals in Connecticut, which expanded Medicaid coverage to a large number of childless adults in April 2010 under the ACA. Using hospital-level panel data from Medicare cost reports, we performed difference-in-differences analyses to compare the change in Medicaid volume and uncompensated care in the period 2007-13 in Connecticut to changes in other Northeastern states. We found that early Medicaid expansion in Connecticut was associated with an increase in Medicaid discharges of 7-9 percentage points, relative to a baseline rate of 11 percent, and an increase of 7-8 percentage points in Medicaid revenue as a share of total revenue, relative to a baseline share of 10 percent. Also, in contrast to the national and regional trends of increasing uncompensated care during this period, hospitals in Connecticut experienced no increase in uncompensated care. We conclude that uncompensated care in Connecticut was roughly one-third lower than what it would have been without early Medicaid expansion. The results suggest that ACA Medicaid expansions could reduce hospitals' uncompensated care burden. PMID- 26153313 TI - Reducing Medicaid Churning: Extending Eligibility For Twelve Months Or To End Of Calendar Year Is Most Effective. AB - Medicaid churning--the constant exit and reentry of beneficiaries as their eligibility changes--has long been a problem for both Medicaid administrators and recipients. Churning will continue under the Affordable Care Act because, despite new federal rules, Medicaid eligibility will continue to be based on current monthly income. We developed a longitudinal simulation model to evaluate four policy options for modifying or extending Medicaid eligibility to reduce churning. The simulations suggest that two options--extending eligibility either to the end of a calendar year or for twelve months after enrollment--would be the most effective methods for reducing churning. The other options--a three-month extension or eligibility based on projected annual income--would reduce churning to a lesser extent. States should consider implementation of the option that best balances costs while improving access to coverage and, thereby, the health of Medicaid enrollees. PMID- 26153314 TI - Health Aid Is Allocated Efficiently, But Not Optimally: Insights From A Review Of Cost-Effectiveness Studies. AB - Development assistance from high-income countries to the health sectors of low- and middle-income countries (health aid) is an important source of funding for health in low- and middle-income countries. However, the relationship between health aid and the expected health improvements from those expenditures--the cost effectiveness of targeted interventions--remains unknown. We reviewed the literature for cost-effectiveness of interventions targeting five disease categories: HIV; malaria; tuberculosis; noncommunicable diseases; and maternal, newborn, and child health. We measured the alignment between health aid and cost effectiveness, and we examined the possibility of better alignment by simulating health aid reallocation. The relationship between health aid and incremental cost effectiveness ratios is negative and significant: More health aid is going to disease categories with more cost-effective interventions. Changing the allocation of health aid earmarked funding could lead to greater health gains even without expanding overall disbursements. The greatest improvements in the alignment would be achieved by reallocating some aid from HIV or maternal, newborn, and child health to malaria or TB. We conclude that health aid is generally aligned with cost-effectiveness considerations, but in some countries this alignment could be improved. PMID- 26153316 TI - Women Saw Large Decrease In Out-Of-Pocket Spending For Contraceptives After ACA Mandate Removed Cost Sharing. AB - The Affordable Care Act mandates that private health insurance plans cover prescription contraceptives with no consumer cost sharing. The positive financial impact of this new provision on consumers who purchase contraceptives could be substantial, but it has not yet been estimated. Using a large administrative claims data set from a national insurer, we estimated out-of-pocket spending before and after the mandate. We found that mean and median per prescription out of-pocket expenses have decreased for almost all reversible contraceptive methods on the market. The average percentages of out-of-pocket spending for oral contraceptive pill prescriptions and intrauterine device insertions by women using those methods both dropped by 20 percentage points after implementation of the ACA mandate. We estimated average out-of-pocket savings per contraceptive user to be $248 for the intrauterine device and $255 annually for the oral contraceptive pill. Our results suggest that the mandate has led to large reductions in total out-of-pocket spending on contraceptives and that these price changes are likely to be salient for women with private health insurance. PMID- 26153315 TI - Simulations Show Diagnostic Testing For Malaria In Young African Children Can Be Cost-Saving Or Cost-Effective. AB - Malaria imposes a substantial global disease burden. It disproportionately affects sub-Saharan Africans, particularly young children. In an effort to improve disease management, the World Health Organization (WHO) recommended in 2010 that countries test children younger than age five who present with suspected malaria fever to confirm the diagnosis instead of treating them presumptively with antimalarial drugs. Costs and concerns about the overall health impact of such diagnostic testing for malaria in children remain barriers to full implementation. Using data from national Malaria Indicator Surveys, we estimated two-stage microsimulation models for Angola, Tanzania, and Uganda to assess the policy's cost-effectiveness. We found that diagnostic testing for malaria in children younger than five is cost-saving in Angola. In Tanzania and Uganda the cost per life-year gained is $5.54 and $94.28, respectively. The costs projected for Tanzania and Uganda are less than the WHO standard of $150 per life year gained. Our results were robust under varying assumptions about cost, prevalence of malaria, and behavior, and they strongly suggest the pursuit of policies that facilitate full implementation of testing for malaria in children younger than five. PMID- 26153317 TI - Wide Variation Found In Hospital Facility Costs For Maternity Stays Involving Low Risk Childbirth. AB - Childbirth is the leading cause of hospital admission in the United States, yet there has been little research on variation in hospital costs associated with childbirth. Using data from the 2011 Nationwide Inpatient Sample, we characterized the variation in estimated facility costs of hospitalizations for low-risk childbirth across US hospitals. We found that the average estimated facility cost per maternity stay ranged from $1,189 to $11,986 (median: $4,215), with a 2.2-fold difference between the 10th and 90th percentiles. Estimated facility costs were higher at hospitals with higher rates of cesarean delivery or serious maternal morbidity. Hospitals having government or nonprofit ownership; being a rural hospital; and having relatively low volumes of childbirths, low proportions of childbirths covered by Medicaid, and long stays also had significantly higher costs. The large variation in estimated facility cost for low-risk childbirths among hospitals suggests that hospital practices might be an important contributor to variation in cost and that there may be opportunities for cost reduction. The safe reduction of cesarean deliveries, increasing the coordination of care, and emphasizing value of care through new payment and delivery systems reforms may help reduce hospital costs and cost variation associated with childbirth in the United States. PMID- 26153318 TI - Tracking Trends In Provider Reimbursements And Patient Obligations. AB - Primary payments--those made by insurance carriers--to office-based physicians rose moderately between 2013 and 2014. Payments declined for orthopedics and surgery while increasing for primary care and obstetrics-gynecology. Patients' payment obligations rose for all specialties, and deductibles were the largest category of increased patient spending. PMID- 26153319 TI - Across State Lines, A Family Navigates Medical Complexity And Medicaid Hurdles. AB - A medically complex child and a military family navigate Medicaid coverage challenges as they travel from state to state. PMID- 26153320 TI - Round Six Of Partners Investing In Nursing's Future: Implications For The Health Sector, Policy Makers, And Foundations. AB - In its 2011 report on the future of nursing, the Institute of Medicine issued recommendations to position nursing to meet the challenges of twenty-first century health care. Following release of the report, the Robert Wood Johnson Foundation funded eleven local and regional partnerships of nurses, foundations, and other stakeholders to begin implementing some of the recommendations in their regions. A qualitative evaluation of these partnerships found that although not all goals were met, most of the partnerships achieved meaningful gains. Partnership participants emphasized the value of engaging foundations and other stakeholders from outside nursing in the implementation process, the necessity of funding for implementation, the need for policy makers to address constraints that local and regional partnerships by themselves cannot address, and the unique leadership and convening role that local and regional foundations can play to help their regions respond to complex challenges for the nursing profession. PMID- 26153322 TI - False-Positive Mammograms, Breast Cancer Overdiagnoses. PMID- 26153323 TI - Breast Cancer Diagnoses: The Authors Reply. PMID- 26153324 TI - Standards Of Care And Best Care. PMID- 26153325 TI - Health Care In Sub-Saharan Africa. PMID- 26153326 TI - Standards Of Care: The Author Replies. PMID- 26153327 TI - Ultra-light Hierarchical Graphene Electrode for Binder-Free Supercapacitors and Lithium-Ion Battery Anodes. AB - A mild and environmental-friendly method is developed for fabricating a 3D interconnected graphene electrode with large-scale continuity. Such material has interlayer pores between reduced graphene oxide nanosheets and in-plane pores. Hence, a specific surface area up to 835 m(2) g(-1) and a high powder conductivity up to 400 S m(-1) are achieved. For electrochemical applications, the interlayer pores can serve as "ion-buffering reservoirs" while in-plane ones act as "channels" for shortening the mass cross-plane diffusion length, reducing the ion response time, and prevent the interlayer restacking. As binder-free supercapacitor electrode, it delivers a specific capacitance up to 169 F g(-1) with surface-normalized capacitance close to 21 MUF cm(-2) (intrinsic capacitance) and power density up to 7.5 kW kg(-1), in 6 m KOH aqueous electrolyte. In the case of lithium-ion battery anode, it shows remarkable advantages in terms of the initiate reversible Coulombic efficiency (61.3%), high specific capacity (932 mAh g(-1) at 100 mA g(-1)), and robust long-term retention (93.5% after 600 cycles at 2000 mAh g(-1)). PMID- 26153328 TI - Enantioseparation tuned by solvent polarity on a beta-cyclodextrin clicked chiral stationary phase. AB - The efficient enantioseparation of 26 racemates has been achieved with the perphenylcarbamoylated cyclodextrin clicked chiral stationary phase by screening the optimum composition of mobile phase in high-performance liquid chromatography. The chromatographic results indicate that both the retention and chiral resolution of racemates are closely related to the polarity of the mobile phases and the structures of analytes. The addition of alcohols can significantly tune the enantioseparation in normal-phase high-performance liquid chromatography. The addition of methanol and the ratio of ethanol/methanol or isopropanol/methanol played a key role on the resolution of flavonoids in ternary eluent systems. The chiral separation of flavonoids with pure organic solvent as mobile phase indicates the preferential order for chiral resolution is methanol>ethanol>isopropanol>n-propanol>acetonitrile. PMID- 26153330 TI - Current and future molecular diagnostics in non-small-cell lung cancer. AB - The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored. PMID- 26153331 TI - Embracing the era of wearable devices. PMID- 26153332 TI - In reference to A novel role for otolaryngologists in the multidisciplinary difficult airway response team. PMID- 26153333 TI - One shot, one kill: the forces delivered by archer fish shots to distant targets. AB - Archer fishes are skillful hunters of terrestrial prey, firing jets of water that dislodge insects perched on overhead vegetation. In the current investigation, we sought an answer to the question: are distant targets impractical foraging choices? Targets far from the shooter might not be hit with sufficient force to cause them to fall. However, observations from other investigators show that archer fish fire streams of water that travel in a non-ballistic fashion, which is thought to keep on-target forces high, even to targets that are several body lengths distant from the fish. We presented targets at different distances and investigated three aspects of foraging behavior: (i) on-target forces, (ii) shot velocity, (iii) a two-target choice assay to determine if fish would show any preference for downing closer targets or more distant targets. In general, shots from our fish (Toxotes chatareus) showed a mild decrease (less than 15% on average) in on-target forces at our most distant target offered (5.8 body lengths) with respect to the closest target offered (2.3 body lengths). One individual in our investigation showed slightly, but significantly, greater on target forces as target distance increased. Forces on the furthest targets offered were found to double that of attachment forces for 200mg insects, even for individuals whose on-target forces showed mild decreases with increases in target distance. High-speed video analysis of jet impact with the target revealed that the shot was traveling in a non-ballistic manner, even to our most distant target offered, corroborating previous suppositions that on-target forces should remain high. Fish were able to accomplish this without large changes to shot velocity, but we did find evidence that the water jets appeared to differ in the timing of their acceleration as target distance increased. Our two-target choice experiment revealed that fish show preference for downing the closer target first, even though impact forces on distant targets only showed mild decreases. Our overall findings (and the findings of others) suggest that archer fish modulate many aspects of their shooting behavior: from target selection to active control over the water jet that allows the fish to deliver reliably forceful impacts to prey over a wide range of distances. PMID- 26153334 TI - Crocodylus niloticus (Crocodilia) is highly sensitive to water surface waves. AB - Crocodiles show oriented responses to water surface wave stimuli but up to now behavioral thresholds are missing. This study determines the behavioral thresholds of crocodilians to water surface waves. Nile crocodiles (Crocodylus niloticus) were conditioned to respond to single-frequency water surface wave stimuli (duration 1150 ms, frequency 15, 30, 40, 60 and 80 Hz), produced by blowing air onto the water surface. Our study shows that C. niloticus is highly sensitive to capillary water surface waves. Threshold values decreased with increasing frequency and ranged between 10.3 MUm (15 Hz) and 0.5 MUm (80 Hz) peak to-peak wave amplitude. For the frequencies 15 Hz and 30 Hz the sensitivity of one spectacled caiman (Caiman crocodilus) to water surface waves was also tested. Threshold values were 12.8 MUm (15 Hz) down to 1.76 MUm (30 Hz), i.e. close to the threshold values of C. niloticus. The surface wave sensitivity of crocodiles is similar to the surface wave sensitivity of semi-aquatic insects and fishing spiders but does not match the sensitivity of surface-feeding fishes which is higher by one to two orders of magnitude. PMID- 26153335 TI - Anesthesia management of a patient with Jervell and Lange-Nielsen syndrome. PMID- 26153336 TI - Breakage of epidural catheter: importance of proper imaging. PMID- 26153337 TI - Duration of clopidogrel-based dual antiplatelet therapy and clinical outcomes after endeavor sprint zotarolimus-eluting stent implantation in patients presenting with acute coronary syndrome. AB - BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) remains controversial in patients with acute coronary syndrome (ACS). We sought to compare outcomes after the implantation of zotarolimus-eluting stent (ZES) between patients with ACS who received clopidogrel-based DAPT for >6months and those treated for <=6months. METHODS: From a registry of patients treated with ZESs between October 2005 and January 2010, 1740 patients with ACS were selected for the present analysis. Landmark analyses were performed for ACS patients who were event-free at 6months follow-up (n=1674). The primary outcome was a major adverse cardiac and cerebrovascular event (MACCE), including all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis, or stroke. We also performed adjustments for the baseline characteristics of patients, using their propensity-score matching (n=469 pairs). RESULTS: During a median follow-up of 22.5months, the rate of MACCE was 6.4% in patients with DAPT >6months (n=1140) and 4.7% in patients with DAPT <=6months (n=534) (adjusted hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.61-1.82; p=0.86). After propensity-score matching, DAPT >6months was not found to be associated with a lower incidence of MACCE compared with DAPT <=6months (adjusted HR 0.80, 95% CI 0.44-1.45, p=0.46). The rates of all-cause death or MI, TVR, stent thrombosis, and stroke also did not differ significantly between two groups. CONCLUSION: DAPT for >6months do not seem to be associated with improved clinical outcomes in patients with ACS undergoing percutaneous coronary intervention (PCI) with ZES. PMID- 26153338 TI - Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry. AB - OBJECTIVE: Hemoglobin A1c (HbA1c) levels among individuals with type 1 diabetes (T1D) influence the longitudinal risk for diabetes-related complications. Few studies have examined HbA1c trends across time in children, adolescents, and young adults with T1D. This study examines changes in glycemic control across the specific transition periods of pre-adolescence-to-adolescence and adolescence-to young adulthood, and the demographic and clinical factors associated with these changes. RESEARCH DESIGN AND METHODS: Available HbA1c lab results for up to 10 yr were collected from medical records at 67 T1D Exchange clinics. Two retrospective cohorts were evaluated: the pre-adolescent-to-adolescent cohort consisting of 85 016 HbA1c measurements from 6574 participants collected when the participants were 8-18 yr old and the adolescent-to-young adult cohort, 2200 participants who were 16-26 yr old at the time of 17 279 HbA1c measurements. RESULTS: HbA1c in the 8-18 cohort increased over time after age 10 yr until ages 16-17; followed by a plateau. HbA1c levels in the 16-26 cohort remained steady from 16-18, and then gradually declined. For both cohorts, race/ethnicity, income, health insurance, and pump use were all significant in explaining individual variations in age centered HbA1c (p < 0.001). For the 8-18 cohort, insulin pump use, age of onset, and health insurance were significant in predicting individual HbA1c trajectory. CONCLUSIONS: Glycemic control among patients 8-18 yr old worsens over time, through age 16. Elevated HbA1c levels observed in 18 yr-olds begin a steady improvement into early adulthood. Focused interventions to prevent deterioration in glucose control in pre-adolescence, adolescence, and early adulthood are needed. PMID- 26153339 TI - Increasing prevalence of asthma, respiratory symptoms, and allergic diseases: Four repeated surveys from 1993-2014. AB - BACKGROUND: Published data shows different prevalence trends depending on the region of Europe. AIM: The aim of the study was to analyze time trends of the frequency of the respiratory symptoms and allergic diseases in school children (Silesia, Poland) over the last 21 years. METHODS: We compared the results of four population-based surveys performed in a town of Chorzow in 1993, 2002, 2007 and 2014 in children aged 7-10 years. All four studies had the same study protocol, recruitment (cluster, school-based sampling), questionnaire (WHO respiratory health questionnaire) and the same principal investigator The surveys included 1130 children in 1993, 1421 children in 2002, 1661 children in 2007 and 1698 in 2014. RESULTS: The results covered a 21 year span and showed a statistically significant (p < 0.05) increase in the prevalence of the following physician-diagnosed disorders (1993-2002-2007-2014): asthma (3.4%-4.8%-8.6% 12,6%); allergic rhinitis (4.3%-11.9%-15.9%-13.9%); atopic dermatitis (3.6%-7.9% 12.0%-13.9%); allergic conjunctivitis (4.3%-7.9%-8.3%-7.9%); A simultaneous increasing trend (p < 0.05) in the attacks of dyspnea (3.9%-5.9%-7.0%-7.3%) and symptoms (wheeze, dyspnea, cough) induced by exercise (7.5%-10.6%-22.0%-22.4%) and - at the same time - decrease (p < 0.05) in the prevalence of cough (31.6% 19.6%15.4%-14.4%). Among children with diagnosed asthma during the 21 year span there was significantly (p < 0.05) increased proportion of treated children (51.3%-51.3%-69.5%-60.7%) and a lower frequency of presenting current symptoms. CONCLUSIONS: Our findings are in line with the concept of a real increase in the occurrence of asthma and allergic disease in children. The pattern involves not only physician-diagnosed allergic diseases but also occurrence of symptoms related to respiratory disorders. Diagnosed asthma is better treated and better controlled. PMID- 26153340 TI - The IDF Life for a Child Program Index of diabetes care for children and youth. AB - BACKGROUND AND OBJECTIVES: Care for children and youth with diabetes varies markedly around the world. We developed a standardized, reproducible measure that can be used to document and compare critical factors influencing treatment outcomes. METHODS: A questionnaire consisting of 36 multiple-choice questions covering major components of care (such as insulin therapy, blood glucose monitoring, etc.) was sent to 75 countries: 43 under-resourced countries where the International Diabetes Federation's Life for a Child Program operates, and 32 others (mainly developed nations). Results for each country were scaled to a score with a range of 0-100. RESULTS: Responses were received from 71 countries. Scores varied widely and were highly correlated to per capita gross domestic product (R(2) = 0.72, P < 0.001) and health expenditure (R(2) = 0.77, P < 0.001). For the 37 low- and lower-middle income countries, only two had complete government provision of human insulin and none of blood glucose test strips. Marked differences according to income were also found for access to home refrigeration; usage of insulin pens, multiple daily injections, pumps, glucagon and ketone strips; hemoglobin A1c (HbA1c) testing; and complications screening. CONCLUSIONS: The index is a comprehensive, easily administered survey instrument. It demonstrated stark differences in access to numerous components of care necessary in achieving good outcomes for children and youth with diabetes. PMID- 26153341 TI - Wurtzite CZTS nanocrystals and phase evolution to kesterite thin film for solar energy harvesting. AB - A quaternary indium- and gallium-free kesterite (KS)-based compound, copper zinc tin sulfide (Cu2ZnSnS4, CZTS), has received significant attention for its potential applications in low cost and sustainable solar cells. It is well known that the reaction time, reactivity of the precursors, and types of capping ligands used during the synthesis of colloidal nanocrystals (NCs) strongly influence the crystallographic phase of the NCs. In this research, a non-toxic and green synthetic strategy for both the synthesis of CZTS NCs and the fabrication of a highly efficient CZTS absorber layers using an ink formulation without a toxic solvent, which meets the comprehensive framework for green chemistry that covers major aspects of the environmental strain, is demonstrated. In particular, pure metastable wurtzite (WZ) CZTS NCs are synthesized using the environmentally harmless, polyol mediated hot-injection (HI) technique at a low reaction temperature. The influence of the reaction time on the properties of the CZTS NCs is investigated in detail. Based on detailed reaction time dependent phase evolution, a possible growth and formation mechanism is proposed. Furthermore, a scalable, low cost, binder free ink formulation process without ligand exchange is developed using ethanol as the dispersal solvent. The as prepared WZ-derived CZTS NC thin films are observed to undergo a phase transformation to KS during annealing in a sulfur vapor atmosphere via rapid thermal annealing above 500 degrees C, and surprisingly, this process results in fully sintered, compact and uniform CZTS thin films with large sized grains. The best solar cell device fabricated using a CZTS absorber that was sulfurized at an optimized temperature exhibits a power conversion efficiency of 2.44%, which is the highest efficiency obtained using the polyol-based HI route. PMID- 26153342 TI - Proteomic analysis of Arabidopsis thaliana (L.) Heynh responses to a generalist sucking pest (Myzus persicae Sulzer). AB - Herbivorous insects can cause severe cellular changes to plant foliage following infestations, depending on feeding behaviour. Here, a proteomic study was conducted to investigate the influence of green peach aphid (Myzus persicae Sulzer) as a polyphagous pest on the defence response of Arabidopsis thaliana (L.) Heynh after aphid colony establishment on the host plant (3 days). Analysis of about 574 protein spots on 2-DE gels revealed 31 differentially expressed protein spots. Twenty out of these 31 differential proteins were selected for analysis by mass spectrometry. In 12 of the 20 analysed spots, we identified seven and nine proteins using MALDI-TOF-MS and LC-ESI-MS/MS, respectively. Of the analysed spots, 25% contain two proteins. Different metabolic pathways were modulated in Arabidopsis leaves according to aphid feeding: most corresponded to carbohydrate, amino acid and energy metabolism, photosynthesis, defence response and translation. This paper has established a survey of early alterations induced in the proteome of Arabidopsis by M. persicae aphids. It provides valuable insights into the complex responses of plants to biological stress, particularly for herbivorous insects with sucking feeding behaviour. PMID- 26153343 TI - Hygroscopic and phase transition properties of alkyl aminium sulfates at low relative humidities. AB - Alkyl aminium sulfates (AASs) can affect the physicochemical properties of atmospheric aerosols such as hygroscopicity. Previous laboratory experiments have shown that the water content in AAS bulk solutions is higher than in aqueous ammonium sulfate solution in the range of 60-95% relative humidity (RH). Furthermore, amine was found to evaporate from the solution during the preparation of AASs from the parent amine and sulfuric acid solutions. Here we report the hygroscopicities of deposited particles of four AASs at different aminium-to-sulfate molar ratios (A/Ss) in the range of <3-90% RH using air-flow cells coupled with in situ micro-Raman spectroscopy. Normalized integrated areas of O-H stretching peaks in the Raman spectra were converted to water-to-solute molar ratios (WSRs) at various RH values. Evaporation of amine was also observed in most cases and the exact A/Ss of sample particles or solutions were determined by ion chromatography. Mono-methylaminium sulfate (MMAS) and mono-ethylaminium sulfate (MEAS) particles were stable at A/S = 2.0, but di-methylaminium sulfate (DMAS) and tri-methylaminium sulfate (TMAS) suffered from DMA and TMA evaporation and eventually equilibrated to the A/S of 1.5 and 1.0, respectively. At these stable compositions MMAS and MEAS exhibited phase transitions in the super saturation region, while DMAS and TMAS showed a continuous and reversible water uptake. Besides, an approach to estimate the hygroscopicities of DMAS and TMAS particles at an initial A/S larger than that of the stable compositions was presented. In the range of 60-95% RH, the WSRs of all the studied AAS particles were consistent with a previous study based on experimental values and the extended Zdanovskii-Stokes-Robinson equation. In general, all the studied AASs were more hygroscopic than their corresponding ammonium counterparts within the studied RH range and evaporation of amine needs to be corrected in studying unstable AAS particles. PMID- 26153344 TI - Excess electron interaction with radiosensitive 5-bromopyrimidine in aqueous solution: a combined ab initio molecular dynamics and time-dependent wave-packet study. AB - Radiation-generated secondary electrons can induce resonance processes in a target molecule and fragment it via different pathways. Although the associating electronic resonant states at equilibrium geometry have been well studied for many target molecules in the gas phase, vibrational resonance contributions and the solvent effect are still poorly understood for relevant processes in solution. Taking a radiosensitive drug, 5-bromopyrimidine (5-BrPy), as an example, we here present a combined ab initio molecular dynamics simulation and time-dependent wave packet study with an emphasis on vibrational resonance and solvation effects on excess electron interaction with 5-BrPy in solution. The gaseous results reveal two primary channels for the electron induced C-Br bond cleavage: the highest vibrational resonance on vertical potential energy curve via a tunneling mechanism (e + 5-BrPy -> 5-BrPy(*-) ->(tunneling) Br(-) + Py(.)), and auto-dissociation along repulsive relaxed potential energy curve (e + 5-BrPy > 5-BrPy(*-) ->(relaxation) Br(-) + Py(.)), which account for the two peaks at 0.2 and 0 eV observed in Modelli's experiment. However, a strong solvation effect modifies the mechanism and dynamics of the dissociation of the electron...5-BrPy system. On one hand, the spontaneous dissociation becomes unfavorable due to a barrier on the relaxed free energy surface created by the coupling between the pi* and sigma* states. Seven vibrational resonances (v = 0-6) are identified for the solution process and only the high-level v = 5, 6 with non-negligible quantum tunneling coefficient can cause the dissociation (e + 5-BrPy ->(localization) 5 BrPy(*-) ->(tunneling) [Br(delta-)...Py(delta-)] ->Br(-) + Py(.)). On the other hand, protonation is also observed at the N sites of the hydrated 5-BrPy anion (e + 5-BrPy ->(localization) 5-BrPy(*-) ->(relaxation) Prt-5-BrPy), and this inhibits the dissociation along the C-Br bond, suggesting a competing pathway against C-Br bond cleavage. Clearly, this work provides a combination strategy using an ab initio molecular dynamics technique and time-dependent wave packet method to explore the effects of vibrational resonances and solvation on the interaction of radio-generated excess electrons with target biological molecules in complicated solution surroundings. PMID- 26153345 TI - Position and orientational preferences of drug-like compounds in lipid membranes: a computational and NMR approach. AB - Permeation of drugs across lipid bilayers is a key factor in dictating how effective they will be. In vivo, the issue is compounded by the presence of drug exporter proteins such as P-glycoprotein. However, despite intense effort, exactly what controls permeation and susceptibility to export is still poorly understood. In this work we examine two well-studied drugs for which interaction with P-glycoprotein has been studied before: amitriptyline, a known substrate and clozapine, which is not a substrate. Extensive MD simulations, including potential of mean force (PMF) profiles of the compounds in all possible protonation states, reveal that the preferred location of the compounds in different bilayers in different protonation states is remarkably similar. For both molecules in charged states, there is a substantial barrier to crossing the bilayer. Clozapine however, shows an energetic barrier to movement across the bilayer even in a protonation state that results in an uncharged molecule. For amitriptyline there is only a very small barrier of approximately 1.3 kcal mol( 1). Further analysis revealed that the conformational and orientational behavior of the two compounds was also similar, with the sidechain interacting with the lipid headgroups. This effect was much stronger if the sidechain was charged (protonated). These interactions with lipid bilayers were confirmed by NMR ROESY experiments. The results are discussed in terms of their potential interactions with export proteins like P-glycoprotein. PMID- 26153346 TI - LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells. AB - In this study, we aimed to investigate the antitumor effect of LYG-202, a newly synthesized piperazine-substituted derivative of flavonoid on human breast cancer cells and illustrate the potential mechanisms. LYG-202 induced apoptosis in MCF 7, MDA-MB-231 and MDA-MB-435 cells. LYG-202 triggered the activation of mitochondrial apoptotic pathway through multiple steps: increasing Bax/Bcl-2 ratio, decreasing mitochondrial membrane potential (DeltaPsi(m)), activating caspase-9 and caspase-3, inducing cleavage of poly(ADP-ribose) polymerase, cytochrome c release and apoptosis-inducing factor translocation. Furthermore, LYG-202 inhibited cell cycle progression at the G1/S transition via targeting Cyclin D, CDK4 and p21(Waf1/Cip1). Additionally, LYG-202 increased the generation of intracellular ROS. N-Acetyl cysteine, an antioxidant, reversed LYG-202-induced apoptosis suggesting that LYG-202 induces apoptosis by accelerating ROS generation. Further, we found that LYG-202 deactivated the PI3K/Akt pathway, activated Bad phosphorylation, increased Cyclin D and Bcl-xL expression, and inhibited NF-kappaB nuclear translocation. Activation of PI3K/Akt pathway by IGF 1 attenuated LYG-202-induced apoptosis and cell cycle arrest. Our in vivo study showed that LYG-202 exhibited a potential antitumor effect in nude mice inoculated with MCF-7 tumor through similar mechanisms identified in cultured cells. In summary, our results demonstrated that LYG-202 induced apoptosis and cell cycle arrest via targeting PI3K/Akt pathway, indicating that LYG-202 is a potential anticancer agent for breast cancer. PMID- 26153347 TI - Laser-induced transformation of supramolecular complexes: approach to controlled formation of hybrid multi-yolk-shell Au-Ag@a-C:H nanostructures. AB - In the present work an efficient approach of the controlled formation of hybrid Au-Ag-C nanostructures based on laser-induced transformation of organometallic supramolecular cluster compound is suggested. Herein the one-step process of the laser-induced synthesis of hybrid multi-yolk-shell Au-Ag@a-C:H nanoparticles which are bimetallic gold-silver subnanoclusters dispersed in nanospheres of amorphous hydrogenated a-C:H carbon is reported in details. It has been demonstrated that variation of the experimental parameters such as type of the organometallic precursor, solvent, deposition geometry and duration of laser irradiation allows directed control of nanoparticles' dimension and morphology. The mechanism of Au-Ag@a-C:H nanoparticles formation is suggested: the photo excitation of the precursor molecule through metal-to-ligand charge transfer followed by rupture of metallophilic bonds, transformation of the cluster core including red-ox intramolecular reaction and aggregation of heterometallic species that results in the hybrid metal/carbon nanoparticles with multi-yolk shell architecture formation. It has been found that the nanoparticles obtained can be efficiently used for the Surface-Enhanced Raman Spectroscopy label-free detection of human serum albumin in low concentration solution. PMID- 26153348 TI - Split-inteins and their bioapplications. AB - Split-inteins are a subset of inteins that are expressed in two separate halves and catalyze splicing in trans upon association of the two domains. They occur naturally and have also been artificially generated by splitting of contiguous ones. With their unique properties, split-inteins offer improved controllability, flexibility and capability to existing tools based on contiguous inteins. In addition, split-inteins have proven useful in several new applications. This review gives a general introduction to split-inteins with a focus on their role in expanding the applications of intein-based technologies. PMID- 26153349 TI - Site-Specific Substitutional Boron Doping of Semiconducting Armchair Graphene Nanoribbons. AB - A fundamental requirement for the development of advanced electronic device architectures based on graphene nanoribbon (GNR) technology is the ability to modulate the band structure and charge carrier concentration by substituting specific carbon atoms in the hexagonal graphene lattice with p- or n-type dopant heteroatoms. Here we report the atomically precise introduction of group III dopant atoms into bottom-up fabricated semiconducting armchair GNRs (AGNRs). Trigonal-planar B atoms along the backbone of the GNR share an empty p-orbital with the extended pi-band for dopant functionality. Scanning tunneling microscopy (STM) topography reveals a characteristic modulation of the local density of states along the backbone of the GNR that is superimposable with the expected position and concentration of dopant B atoms. First-principles calculations support the experimental findings and provide additional insight into the band structure of B-doped 7-AGNRs. PMID- 26153350 TI - Engaging novice researchers in the process and culture of science using a "Pass the-Problem" case strategy. AB - Undergraduates having their first research experience frequently have little idea of what to expect. Institutions offering summer research experiences attempt to address this issue through programs that introduce students to the process and culture of science. However, didactic approaches frequently bore students who prefer more interactive sessions. We describe a "Pass-the-Problem" case study approach that engages groups of students in useful discussions about the research environment they are entering. The cases presented here include keeping a thorough laboratory notebook, balancing laboratory and personal time demands, anxiety about formal presentations, unexpected federal regulatory inspection, working in a lab with limited funds, being used as a technician rather than a researcher, frustration with failed experiments, effects of promotion and tenure on laboratory atmosphere, the importance of reading the research literature, and questioning a career in science. These cases alert students to different situations they might encounter and stimulate discussion about how to deal with them. PMID- 26153352 TI - A streamlined Western blot exercise: An efficient and greener approach in the laboratory classroom. AB - SDS-PAGE and western blotting are two commonly taught protein detection techniques in biochemistry and molecular biology laboratory classrooms. A pitfall associated with incorporating these techniques into the laboratory is the significant wait times that do not allow students to obtain timely results. The waiting associated with SDS-PAGE comes from staining and destaining, whereas with western blotting it is the times required for antibody incubations and the numerous wash steps. This laboratory exercise incorporates 2,2,2-trichloroethanol (TCE) into the SDS-PAGE gel allowing for visualization of migrated proteins in a matter of minutes, saving both the time and chemical waste associated with traditional Coomassie staining. Additionally, TCE staining does not affect protein transfer eliminating the requirement for duplicated gels for total protein and western analyses. Protein transfer can be confirmed immediately without the use of Ponceau S staining. Lastly, this western blot procedure has been further shortened by using an HRP-conjugated primary antibody, which eliminates the secondary antibody incubation and washes, and uses a colorimetric detection to allow for visualization by students without the need for specialized equipment. PMID- 26153353 TI - Robotic inguinal hernia repair. AB - Inguinal hernias have been described throughout the history of medicine with many efforts to achieve the cure. Currently, with the advantages of minimally invasive surgery, new questions arise: what is going to be the best approach for inguinal hernia repair? Is there a real benefit with the robotic approach? Should minimally invasive hernia surgery be the standard of care? In this report we address these questions by describing our experience with robotic inguinal hernia repair. PMID- 26153354 TI - Reinitiation at non-canonical start codons leads to leak expression when incorporating unnatural amino acids. AB - With the rapid development of a continuously growing selection of unnatural amino acids (UAAs), UAA insertion becomes increasingly popular for investigating proteins. However, it can prove problematic to ensure the homogeneity of the expressed proteins, when homogeneity is compromised by "leak expression". Here, we show that leak expression may be mediated by reinitiation and can result in unwanted proteins when stop codons for UAA insertion are mutated into the N terminus of proteins. We demonstrate that up to 25% of leak expression occurs through reinitiation in the Shaker-Kv channel when stop codons are located within the first 70 amino acids. Several non-canonical start codons were identified as translation reinitaition sites, and by removing the start codons, we were able to decrease leak expression to less than 1%. Our study emphasizes the need to carefully inspect for leak expression when inserting UAAs and demonstrates how leak expression can be eliminated. PMID- 26153356 TI - Colorectal cancer with peritoneal metastases: Progress, not perfection. PMID- 26153355 TI - The indolent nature of pulmonary metastases from ductal adenocarcinoma of the pancreas. AB - BACKGROUND AND OBJECTIVES: The natural history of pulmonary metastases from pancreatic ductal adenocarcinoma (PDAC) is not well studied. Limited evidence suggests patients with isolated pulmonary metastases from PDAC follow a more benign clinical course than those with other sites of metastases. METHODS: We performed a retrospective review of all patients with pulmonary metastases from PDAC from 2000 to 2010 and analyzed survival utilizing the Kaplan-Meier method based upon location of first metastasis (lung first, intra-abdominal first, or synchronous intra-abdominal and lung metastases). RESULTS: Median survival among subjects with lung as the only site of metastases was significantly longer than those with other metastatic patterns. In subjects that had undergone resection of their PDAC, survival in those with lung as a first site of recurrence remained significantly longer than those with abdominal first or synchronous intra abdominal and lung recurrence. Among resected patients that developed lung only recurrence, survival was significantly prolonged (67.5 months) in those who underwent surgical resection/stereotactic radiosurgery compared to chemotherapy (33.8 months) or observation (29.9 months) for treatment of lung recurrence. CONCLUSION: Patients with isolated pulmonary recurrence from PDAC may realize a survival benefit from surgical intervention or stereotactic radiosurgery compared to chemotherapy or observation for treatment of lung recurrence. PMID- 26153357 TI - Obesity prevalence in Norwegian adults assessed by body mass index, waist circumference and fat mass percentage. AB - The prevalence of obesity presents serious public health challenges worldwide and is most commonly estimated by the categorization of body mass index (BMI). The purpose of this study was (i) to describe the sensitivity of BMI, waist circumference (WC) and fat mass percentage in the classification of overweight and obesity and (ii) to describe the prevalence of overweight and obesity using different measurement methods in a national sample of Norwegians. A total of 904 Norwegians (20-85 years) were randomly enrolled. Body weight, height, WC and skinfold thickness were measured; BMI and fat mass percentage (FP(skf) ) were calculated. The sensitivity and specificity varied from 77.0% to 86.9% and from 60.6% to 82.3%, respectively. Area under the curve was 0.837 (95% confidence interval [CI]: 0.801-0.872) for the ability of BMI to predict obesity by FP(skf) and 0.811 (95% CI: 0.770-0.852) for WC. A total of 12.7% (male: 12.1%, female: 13.4%) were obese based on BMI classifications, 29.1% (male: 36.5%, female: 20.0%) of the sample were obese based on FP(skf) and 24.3% of men and 37.8% of women were abdominally obese by WC. The agreement between selected measuring methods was fair to good, although the variation in obesity prevalence rates between the different assessments methods varied markedly. PMID- 26153359 TI - Editorial: On the cusp of rational CHO cell engineering. AB - With the emergence of additional data on genomic variants, a more detailed molecular understanding of cellular processes and enhanced capabilities in fine tuned manipulation of cell behaviour, the coming years promise to be exciting game changers in the production of therapeutics in mammalian cells. PMID- 26153360 TI - Correction to: A combined cell-free transcription-translation system from Saccharomyces cerevisiae for rapid and robust protein synthe. PMID- 26153362 TI - Engineering a branch of the UDP-precursor biosynthesis pathway enhances the production of capsular polysaccharide in Escherichia coli O5:K4:H4. AB - Escherichia coli K4 produces a capsule with a chemical structure that resembles chondroitin, a molecule with established chondro protective properties. The endogenous genes pgm and galU are involved in the biosynthesis of UDP-glucose which is a critical intermediate in carbohydrate metabolism and biochemical precursor of UDP-glucuronic acid. Together with UDP-N-acetylgalactosamine, UDP glucuronic acid is used as sugar donor for capsule biosynthesis. The aim of the study was to evaluate how a change in the pathways leading to UDP-glucuronic acid biosynthesis affected capsular polysaccharide production. One additional copy of pgm and galU was introduced in E. coli K4 and in the previously described recombinant strain EcK4r3. A microbioreactor was used to analyse strain performance with parallel batch experiments, demonstrating increased polysaccharide concentrations and providing data that are comparable to those obtained in larger fermenters. Further experiments on a glutamine enriched medium showed an additional 45% increase of capsule production, maybe indicating the need to balance both branches leading to polymer biosynthesis in order to maximize yields. In the effort towards the establishment of a feasible bio chondroitin production process this study provides information on how the availability of sugar precursors impacts polysaccharide biosynthesis in E. coli K4, a complex unexplored aspect of a multifaceted process. PMID- 26153363 TI - Empowered to Play: A Case Study Describing the Impact of Powered Mobility on the Exploratory Play of Disabled Children. AB - Exploratory play is one of the most vital ways in which children learn about their environment and develop. It is well documented that limited mobility restricts a child's ability to engage in their environment through exploratory play. In this study, a qualitative, collective case study design explored the impact of powered mobility on the exploratory play of two children with physical disabilities. Data were collected from the children, their parents and their siblings through participant observation and in-depth, informal interviews. This paper focuses on two themes: Opportunity to Play revealed how powered mobility increased opportunities for the children to become more actively engaged in exploratory play with others across a wider array of contexts, and My Child was Transformed highlighted significant changes in the affect and motivation of each child, which seemed to be linked to their increased internal control over their play choices. The findings suggest that the provision of powered mobility is a key contributor promoting the participation of physically disabled children in exploratory play. Because of undergraduate curricular constraints, a limitation of this study was that data were only confined to 2 months; affecting the depth of data gained that prolonged engagement would have offered. The study recommends for occupational therapy practice that occupational therapists advocate for easier access to powered mobility through governmental and policy means. The study also recommends further research be conducted on the experiences of the caregivers on how these powered mobility devices have influenced their day-to-day occupations. PMID- 26153364 TI - Pathogenic diversity amongst serotype C VGIII and VGIV Cryptococcus gattii isolates. AB - Cryptococcus gattii is one of the causative agents of human cryptococcosis. Highly virulent strains of serotype B C. gattii have been studied in detail, but little information is available on the pathogenic properties of serotype C isolates. In this study, we analyzed pathogenic determinants in three serotype C C. gattii isolates (106.97, ATCC 24066 and WM 779). Isolate ATCC 24066 (molecular type VGIII) differed from isolates WM 779 and 106.97 (both VGIV) in capsule dimensions, expression of CAP genes, chitooligomer distribution, and induction of host chitinase activity. Isolate WM 779 was more efficient than the others in producing pigments and all three isolates had distinct patterns of reactivity with antibodies to glucuronoxylomannan. This great phenotypic diversity reflected in differential pathogenicity. VGIV isolates WM 779 and 106.97 were similar in their ability to cause lethality and produced higher pulmonary fungal burden in a murine model of cryptococcosis, while isolate ATCC 24066 (VGIII) was unable to reach the brain and caused reduced lethality in intranasally infected mice. These results demonstrate a high diversity in the pathogenic potential of isolates of C. gattii belonging to the molecular types VGIII and VGIV. PMID- 26153366 TI - Evaluation of the frequency of G-765C polymorphism in the promoter region of the COX-2 gene and its correlation with the expression of this gene in the endometrium of women with endometriosis. AB - OBJECTIVE: To evaluate the frequency of polymorphism G-765C (rs20417) of the COX 2 gene and the expression of this gene in the endometrium of women with endometriosis. STUDY DESIGN: This is a case-control study of 365 women with endometriosis (251 infertile and 114 fertile) submitted to laparoscopy/laparotomy with histological confirmation of endometriosis. The control group was composed of 522 fertile women without endometriosis. Of these, 37 patients from the endometriosis group and 47 from the control group were submitted to biopsy of the endometrium for analysis of the expression of the COX-2 gene. The genotypes were determined using analysis by High-Resolution Melt. Gene expression was measured by qRT-PCR with TaqMan methodology using the GAPDH gene as normalizer of the reactions. RESULTS: The distribution of the genotypes and alleles in the group of fertile women with moderate/severe endometriosis showed a statistically significant difference, demonstrating association of the ancestral allele, -765G, with increased risk of endometriosis (p = 0.028; OR 0.53; CI 0.32-0.90). The mean expression of the COX-2 gene (mRNA PTGS2) in the group of women with endometriosis was statistically higher compared to the control group (3.85 versus 2.84, p = 0.028). CONCLUSION: The present study identified that in Brazilian women the presence of the ancestral allele, -765G, of the COX-2 gene is associated with an increased risk for development of moderate/severe endometriosis associated with fertility, and that the eutopic endometrium of women with endometriosis showed increased expression of COX-2 when compared to the control group. PMID- 26153365 TI - Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up. AB - This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone (VTD) and VTD cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1.3 mg/m(2); days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m(2); days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64.8 months, median time-to-next therapy was 51.8 and 47.9 months with VTD and VTDC, respectively. Type of subsequent therapy was similar in both arms. After adjusting for asymmetric censoring, median time to progression was not significantly different between VTD and VTDC [35.7 vs. 34.5 months; Hazard ratio (HR) 1.26, 95% confidence interval: 0.76-2.09; P = 0.370]. Five-year survival was 69.1% and 65.3% with VTD and VTDC, respectively. When analysed by minimal residual disease (MRD) status, overall survival was longer in MRD negative versus MRD-positive patients with bone marrow-confirmed complete response (HR 3.66, P = 0.0318). VTD induction followed by transplantation provides long-term disease control and, consistent with the primary analysis, there is no additional benefit from adding cyclophosphamide. This study was registered at ClinicalTrials.gov (NCT00531453). PMID- 26153367 TI - Occupation-based intervention in hand injury rehabilitation: Experiences of occupational therapists in Malaysia. AB - INTRODUCTION: In a previous study consensus was sought from Malaysian occupational therapists of occupation-based intervention (OBI) that was perceived as a means and an end. Occupation as a means refers to occupational and purposeful tasks as a therapeutic agent while occupation as an end refers to occupation as an outcome of intervention. The purpose of this follow-up study was to describe the occupational therapists' experiences of providing OBI in hand injury rehabilitation in Malaysia. METHODS: Sixteen occupational therapists with more than five years of experience in hand rehabilitation were individually interviewed on their experiences of using OBI in practice. Data were thematically analysed using interpretative phenomenological analysis. RESULTS: Definition of "Occupation as a means", and "Occupation as an end" was broadened after data analysis of interviews to include two new themes: "Rewarding yet challenging" and "Making OBI a reality". Occupational therapists had positive experiences with OBI and perceived that occupation as a means and an end can be merged into a single therapy session when the occupational therapists use an occupation that is therapeutic. CONCLUSION: Although occupation as a means and as an end have different purposes, when the ultimate goal is to enhance the clients' maximum level of functioning both can be used for successful rehabilitation of hand injuries. PMID- 26153368 TI - The ImageJ ecosystem: An open platform for biomedical image analysis. AB - Technology in microscopy advances rapidly, enabling increasingly affordable, faster, and more precise quantitative biomedical imaging, which necessitates correspondingly more-advanced image processing and analysis techniques. A wide range of software is available-from commercial to academic, special-purpose to Swiss army knife, small to large-but a key characteristic of software that is suitable for scientific inquiry is its accessibility. Open-source software is ideal for scientific endeavors because it can be freely inspected, modified, and redistributed; in particular, the open-software platform ImageJ has had a huge impact on the life sciences, and continues to do so. From its inception, ImageJ has grown significantly due largely to being freely available and its vibrant and helpful user community. Scientists as diverse as interested hobbyists, technical assistants, students, scientific staff, and advanced biology researchers use ImageJ on a daily basis, and exchange knowledge via its dedicated mailing list. Uses of ImageJ range from data visualization and teaching to advanced image processing and statistical analysis. The software's extensibility continues to attract biologists at all career stages as well as computer scientists who wish to effectively implement specific image-processing algorithms. In this review, we use the ImageJ project as a case study of how open-source software fosters its suites of software tools, making multitudes of image-analysis technology easily accessible to the scientific community. We specifically explore what makes ImageJ so popular, how it impacts the life sciences, how it inspires other projects, and how it is self-influenced by coevolving projects within the ImageJ ecosystem. PMID- 26153369 TI - Atypical lymphocytes and eosinophilia in primary cytomegalovirus mononucleosis. PMID- 26153370 TI - Viewpoints - a new addition to the New Phytologist Forum. PMID- 26153371 TI - Growth inhibition by self-DNA: a phenomenon and its multiple explanations. PMID- 26153372 TI - The evolution of the shoot apical meristem from a gene expression perspective. PMID- 26153374 TI - Corrigendum. PMID- 26153375 TI - Erratum. PMID- 26153373 TI - A roadmap for research on crassulacean acid metabolism (CAM) to enhance sustainable food and bioenergy production in a hotter, drier world. AB - Crassulacean acid metabolism (CAM) is a specialized mode of photosynthesis that features nocturnal CO2 uptake, facilitates increased water-use efficiency (WUE), and enables CAM plants to inhabit water-limited environments such as semi-arid deserts or seasonally dry forests. Human population growth and global climate change now present challenges for agricultural production systems to increase food, feed, forage, fiber, and fuel production. One approach to meet these challenges is to increase reliance on CAM crops, such as Agave and Opuntia, for biomass production on semi-arid, abandoned, marginal, or degraded agricultural lands. Major research efforts are now underway to assess the productivity of CAM crop species and to harness the WUE of CAM by engineering this pathway into existing food, feed, and bioenergy crops. An improved understanding of CAM has potential for high returns on research investment. To exploit the potential of CAM crops and CAM bioengineering, it will be necessary to elucidate the evolution, genomic features, and regulatory mechanisms of CAM. Field trials and predictive models will be required to assess the productivity of CAM crops, while new synthetic biology approaches need to be developed for CAM engineering. Infrastructure will be needed for CAM model systems, field trials, mutant collections, and data management. PMID- 26153376 TI - Comorbidities in patients with all-positive symptoms on sinonasal outcomes test quality-of-life instrument. AB - OBJECTIVES/HYPOTHESIS: The Sinonasal Outcomes Test-20 (SNOT-20) is a validated tool to assess treatment outcomes in patients with chronic rhinosinusitis (CRS). In the clinic, we observed that patients who responded with a positive score on all 20 items of the SNOT-20 questionnaire (pan-positive patients) often did not have evidence of CRS upon workup. Many of these patients had other underlying diseases contributing to their complaints. METHODS: Analysis of prospectively collected data was performed to identify SNOT-20 pan-positive patients and compare them to 100 consecutive non-pan-positive patients who served as the control group. The following parameters were compared between the two patient groups: presence or absence of chronic diseases such as obstructive sleep apnea, depression, anxiety, fibromyalgia, chronic pain, headaches, temporomandibular joint disease, and arthritis--in addition to sinus computed-tomography Lund-McKay scores and nasal endoscopy Lund-Kennedy scores. We also reviewed the medication list of each patient to look for the possible presence of mental illness. Statistical analysis was performed using the chi-squared and Student t test. RESULTS: One hundred twenty-two pan-positive patients were identified in our database collected from 2003 to 2011. Pan-positive patients had higher incidence of depression, fibromyalgia, anxiety, pain, headache, and use of depression medications--and they also had higher SNOT-20 and endoscopy scores when compared to controls (P < 0.05). Pan-positive patients were more likely female (P < 0.05), but age and race differences did not reach statistical significance. CONCLUSION: The SNOT-20 questionnaire assists clinicians to monitor outcomes in patients treated for CRS. However, clinicians should suspect other underlying chronic conditions in SNOT-20 pan-positive patients. LEVEL OF EVIDENCE: 3B. PMID- 26153377 TI - Dysphagia and health-related quality of life in patients with eosinophilic esophagitis: a long-term follow-up. AB - Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated disease, with dysphagia as the main symptom. The aim of this study was to survey symptoms and health-related quality of life in adult patients with EoE at least 1 year after diagnosis and a 2-month course of topical corticosteroids. Forty-seven consecutive patients [79 % males, mean age 49 years (range 18-90 years)] were evaluated using three different questionnaires at three different occasions: the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Module 18 (EORTC QLQ-OES18) and the Short Form-36 (SF-36). The median time from diagnosis to the long-term follow-up was 23 months (range 12-34 months). The WDS scores and the EORTC QLQ-OES18 Dysphagia and Eating scale scores were improved after 2 months of treatment (p = 0.00007, p = 0.01, p = 0.004, respectively), as were the long-term follow-up scores (p = 0.01, p = 0.03, p = 0.005, respectively), relative to the scores at diagnosis. In addition, the EORTC QLQ-OES18 Choking scores were improved after the steroid course (p = 0.003) but not after the long-term follow up. No significant differences were detected with respect to the SF-36 scores. In summary, EoE seems to be associated with a substantial burden of symptoms that improve significantly after treatment. A partial remission persists more than 1 year after diagnosis and the discontinuation of medication. The WDS and the EORTC QLQ-OES18 appear to be sensitive instruments appropriate for surveillance in these patients. PMID- 26153378 TI - The rationale for preventive treatments for early post-tympanostomy tube otorrhea in persistent otitis media with effusion. AB - Some studies have shown that post-tympanostomy tube otorrhea (PTTO) is a common complication after tympanostomy tube insertion. There are wide range of controversies about the incidence of PTTO and different methods of preventive treatment. The aim of this study was to determine the incidence of early PTTO in persistent otitis media with effusion in our centers. We also investigated the effect of preventive treatments on the incidence of early PTTO in children with persistent otitis media with effusion. This multi-central study comprised 536 ears belonging to children with otitis media and effusion for at least 3 months, referred for complications arising from post-tympanostomy tube insertion. The patients were randomly divided into three treatment and control groups. In the first group of patients, the middle ear cavity was irrigated with isotonic saline after myringotomy. The second group received oral amoxicillin three times a day for 7 days postoperatively. The third group had similar treatment as the second group, in addition to topical ciprofloxacin drop, 4 drops three times a day for 3 days after operation. The control group did not undergo any treatment. Early post tympanostomy tube otorrhea was detected in 6 ears (1.1 %), including 3 (2.2 %) from the control group and 3 (2.3 %) from the first group. There was no statistically significant difference in early PTTO between integrated treatment groups and control group (P = 0.111). As the total rate of early post tympanostomy tube otorrhea was very low, there was no significant difference between the 3 treatment groups and control group. Our study did not support the routine use of preventive therapy. A period of at least 3 months watchful waiting before tympanostomy tube insertion may help reduce the incidence of PTTO. PMID- 26153380 TI - Systematic review of site of obstruction identification and non-CPAP treatment options for children with persistent pediatric obstructive sleep apnea. AB - OBJECTIVES/HYPOTHESIS: Although adenotonsillectomy is accepted as a first-line therapy for pediatric obstructive sleep apnea (OSA), there is currently no consensus regarding optimal methods for identifying the sites of obstruction or treatment of children with persistent disease after surgery. With this in mind, our aim was to systematically review the English-language literature pertaining to these issues. STUDY DESIGN: Systematic review. METHODS: We searched all indexed years of Pubmed, Cochrane CENTRAL, DynaMed, UpToDate, CINAHL, and Scopus for English-language articles containing original human data, with >= 7 participants, all < 18 years old. Data regarding study design, demographics, clinical characteristics/outcomes, level of evidence, and risk of bias were obtained. Articles were independently reviewed by two investigators. RESULTS: Of 758 identified abstracts, 24 articles (combined population = 960) were ultimately included. Seventeen (71%) described methods to identify site(s) of obstruction: drug-induced sleep endoscopy (11/24), cine magnetic resonance imaging (MRI) (3/24), and alternative imaging (3/24). Treatment options included lingual tonsillectomy (n = 6), with success rates of 57% to 88% (Cohen's effect size d = 1.38), as well as supraglottoplasty (n = 4), with success rates of 58% to 72% (d = 0.64). Additional treatments included medications and surgery (e.g., partial midline glossectomy and tongue suspension). CONCLUSIONS: Drug-induced sleep endoscopy and cine MRI are the most commonly reported tools to identify sites of obstruction for children with persistent OSA; however, these techniques have not yet been clearly linked to outcomes. Evidence for treatment is extremely limited and focuses primarily on lingual tonsillectomy and supraglottoplasty. Also, reports regarding appropriate patient selection and outcomes in obese or otherwise healthy children are scant. PMID- 26153379 TI - ZPAC is required for normal spermatogenesis in mice. AB - The ubiquitin-proteasome pathway, involved in genetic recombination and sex chromosome silencing during meiosis, plays critical roles in the specification of germ-line stem cells and the differentiation of gametes from gonocytes. Zygote specific proteasome assembly chaperone (ZPAC) is expressed in the early mouse embryo, where it is important for progression of the mouse maternal-to-zygotic transition. The role of ZPAC during spermatogenesis in the adult gonads, however, remains unknown. In this study, rapid amplification of cDNA ends was used to determine the Zpac cDNA sequence, a 1584-bp transcript that includes a putative 1122-bp open reading frame coding for a 373 amino acid protein. Western blot and immunohistochemistry revealed that ZPAC was specifically expressed in gonads. To further dissect the function of ZPAC during spermatogenesis, we employed PiggyBac based RNA interference vectors for transgenesis combined with cell transplantation to deplete Zpac during spermatogenesis. This RNAi-mediate depletion in Zpac expression disrupted normal spermatogenesis from spermatogonial stem cells. Two independent yeast two-hybrid screens further revealed an interaction between ZPAC and SYCE1. Together, these data suggest that ZPAC is required for normal spermatogenesis in mice. PMID- 26153381 TI - Accumulation of three important bioactive compounds in different plant parts of Withania somnifera and its determination by the LC-ESI-MS-MS (MRM) method. AB - A comprehensive experiment was conducted to study the accumulation pattern and determination of three important bioactive compounds namely withaferin-A (WA), 12 deoxywithastramonolide (WO) and withanolide-A (WD) and its determination by the liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS MS) method in root, stem, fruits and leaves of Withania somnifera. A rapid and sensitive LC-ESI-MS-MS method was developed and validated for the determination of these three important bioactive compounds, having same molecular weight. The multiple reaction monitoring method was established by two transitions for each analyte and intense transition used for quantification. Separation of the three analytes was achieved within a run time of 5 min on an RP-18 column using a mobile phase consisting of acetonitrile and 0.1% acetic acid in water in an isocratic condition. The developed method was validated as per the ICH guidelines. The developed method was found to be suitable for identification and quantification of WA, WO and WD in different plant parts such as roots, stems, fruits and leaves of W. somnifera. The accumulation of WA was highest in leaves samples (8.84 +/- 0.37 mg/g) and it was 2.23, 5.85 and 27.26 times higher than its concentration in fruits, stems and roots, respectively. WO and WD contents were highest (0.44 +/- 0.016 and 0.72 +/- 0.016 mg/g, respectively) in root. PMID- 26153382 TI - Solid-phase extraction coupled with HPLC-DAD for determination of B vitamin concentrations in halophytes. AB - In our study, a simple and sensitive method was proposed for determination of vitamins B group in leaves of Suaeda aegyptiaca and Suaeda Vera (Halophytes) by HPLC-DAD with solid-phase extraction (SPE) as the preconcentration step. The variables affecting the extraction and determination conditions were investigated and optimized. A preconcentration step based on SPE is necessary to remove interfering components. The limit of detection obtained was <5 mg kg(-1), the relative standard deviation (RSD) was <4%, and the recovery was in the range of 91-102%. The linear correlation coefficient was 0.999. The method was successfully applied to determine group B vitamins in the halophyte samples. As a whole, these findings may confirm the interesting potential of this halophyte as a valuable source of natural bioactive molecules. PMID- 26153383 TI - Ectopic Intrathoracic Kidney Presenting as Recurrent Pneumonias in a 1-year-old Infant: A Case Report. AB - Ectopic intrathoracic kidney is a rare congenital anomaly, representing less than 5% of all renal ectopias. Most cases are discovered in asymptomatic adult patients undergoing imaging exams for unrelated reasons. Less than twenty cases of thoracic kidneys in the infant group have been reported in the literature, mostly comprising asymptomatic patients. Herein, we report a case of an 18-month old boy with recurrent pneumonia episodes who was found to have a right-sided intrathoracic ectopic kidney. A brief literature review addressing the pathogenesis, prognosis, and treatment of this condition is also presented. PMID- 26153384 TI - Examining gender specificity of sexual response with concurrent thermography and plethysmography. AB - Men's genital responses are significantly greater to sexual stimuli of their preferred gender compared to their nonpreferred gender (gender-specific), whereas androphilic (i.e., sexually attracted to men) women's genital responses are similar to sexual stimuli depicting either women or men (gender-nonspecific). This gendered pattern of genital response has only been demonstrated using vaginal photoplethysmography (VPP) in women and primarily penile plethysmography (PPG) in men. These measures assess different aspects of genital vasocongestion, thereby limiting comparisons between genders. Thermography is a newer sexual psychophysiology methodology that measures genital vasocongestion via temperature change and is better suited to assess sexual response between genders because the dependent measure, change in genital temperature, is similar for women and men. Further, previous studies have assessed gender specificity of sexual response across relatively short sexual stimuli, allowing only the examination of initial phases of sexual response. We examined gender specificity of sexual arousal by measuring women's and men's genital responses to lengthier stimuli with concurrent thermography and VPP/PPG. Gynephilic men (i.e., sexually attracted to women; n = 27) and androphilic women (n = 28) viewed 10-min films depicting men masturbating, women masturbating, and a nonsexual film, and reported feelings of sexual arousal while genital responses were assessed. Across measures, men's sexual responses were gender-specific and women's responses were gender nonspecific, indicating that the gender difference in gender specificity of arousal is robust to methodology and stimulus duration. These findings replicate previous research, extend knowledge of gendered sexual response, and highlight the utility of multimethod approaches in sexual psychophysiology. PMID- 26153385 TI - Traumatic asphyxia in the young. PMID- 26153386 TI - Response to Byard's letter "traumatic asphyxia in the young". PMID- 26153387 TI - Improved spoiling efficiency in dynamic RF-spoiled imaging by ghost phase modulation and temporal filtering. AB - PURPOSE: Radiofrequency-spoiled steady-state sequences offer rapid data acquisition with T1- or T2*-weighting. The spoiler gradients in these sequences must be large enough to suppress ghost artifacts, and are chosen empirically. However, certain factors such as the need to minimize gradient first moments or acoustic noise can limit the spoiler size and, hence, the ability to suppress ghosts. We present an acquisition and preprocessing strategy for improved spoiling efficiency in conventional and echo-shifted dynamic radiofrequency spoiled 3D imaging. THEORY AND METHODS: By requiring each time-frame in a dynamic imaging sequence to contain a particular (restricted) number of total radiofrequency shots, the ghost signal can be made to alternate in sign every other frame. The ghost is then suppressed by Fourier transforming along the temporal dimension, and removing the Nyquist frequency in preprocessing (similar to UNFOLD). The method works for both Cartesian and non-Cartesian imaging. RESULTS: We demonstrate improved ghost suppression with the proposed approach, for both conventional and echo-shifted spoiled gradient echo imaging in stationary phantoms and in vivo. Cartesian echo-shifted spoiled gradient echo imaging produces two ghosts shifted in opposite directions, both of which are suppressed with our method. CONCLUSION: For a given spoiler gradient area, the proposed approach substantially suppresses the ghost signal in both conventional and echo-shifted dynamic radiofrequency-spoiled imaging. Magn Reson Med 75:2388 2393, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26153388 TI - Knowledge management practices in healthcare settings: a systematic review. AB - Knowledge is an intangible asset in Organizations, and provides a comparative advantage to those who possess it. Hospitals are complex organizations with unique characteristics because of the heterogeneity of health professionals' orientation, the composite networking and the decision-making processes. A deeper understanding of knowledge management (KM) could streamline productivity and coordinate the use of resources more efficient. We conducted a systematic literature search of peer-reviewed papers that described key elements of KM using three databases (Medline, Cinahl and Health Source: nursing/academic edition) for a 10-year period (1/1/2004-25/11/2014). The included articles were subjected to qualitative content analysis. We retrieved 604 articles of which 20 articles were eligible for analysis. Most of the studies (n=13) used a qualitative methodology. The total sample size was 2155 participants. The key elements that arose were as follows: perceptions of KM, synthesis, dissemination, collaboration, means of KM and leadership. Moreover, this study identified barriers for KM implementation, like time restrictions and limited skills. Healthcare managers ought to cultivate a knowledge environment, operate as role models, provide the tools for KM and reward people who act as knowledge brokers. Opportunities for collaboration and knowledge sharing should be encouraged. Successful KM should be patient-centered to gain its maximum value. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26153389 TI - Immunotherapy for multiple myeloma: Current status and future directions. AB - Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies and has been in the limelight of fast-track development of novel drugs that have contributed to the transformation of a rapidly lethal disease into a chronic illness with significant improvement in quality of life. Nonetheless, MM remains an incurable disease in many patients. Immunotherapy has been one of the approaches that had the highest hope for curing this disease. More than two decades of research and clinical trials in immunotherapy for MM have however resulted in very little impact on patient survival. The various immunotherapy approaches that have been attempted over the last two decades but were fraught with failure have already been extensively summarized in many published reviews. Nevertheless, in view of better understanding of the immune checkpoints, the innate immune system, and improved biotechnology, there is renewed hope. In this review, we will briefly discuss the unsuccessful approaches and emphasize the lessons learned, highlight the challenges that lie ahead, and discuss the more promising approaches, that already exist or being developed such as use of allogeneic stem cell transplants (allo-SCT) as a form of cellular immunotherapy, new monoclonal antibodies, chimeric antigen receptor (CAR) T-cell adoptive therapy, and NK cell therapy. PMID- 26153390 TI - Experience and Outcome of Children with Severe Acute Malnutrition Using Locally Prepared Therapeutic Diet. AB - OBJECTIVE: Globally more than 1/3rd of the child deaths are attributed to under nutrition and it continues to be a major public health problem in developing countries. This research paper is an attempt towards intervention and management of severely malnourished children with the use of locally prepared therapeutic diets to bring down the case fatality rate. METHODS: A cross-sectional longitudinal study was undertaken at a tertiary care hospital in North India. Children under 5 y of age fulfilling the WHO case definition of severe acute malnutrition and suffering from medical complications were enrolled and managed on standard WHO protocols using locally prepared therapeutic diet (Starter F-75 diet and Catch-up F-100 diet). RESULTS: During the period of 11 mo, a total of 315 children (192 boys and 123 girls) under 5 y with severe acute malnutrition requiring in-patient care were enrolled and evaluated. The overall case fatality rate was 3.5% while average weight gain seen was 9.33 +/- 8.28 g/kg body weight/day and average length of stay was 11.71 +/- 7.59. The Nutrition Rehabilitation Centre (NRC) observed a cure rate of 47% and secondary failure rate of 19%. CONCLUSIONS: The present study highlights the integral role of locally prepared therapeutic diet (starter F-75 and F-100) besides standardized care provided at Nutrition Rehabilitation Centre (NRC) to combat malnutrition which is a major scourge in the developing world. To sustain the benefits and prevent relapse, there is a need to integrate the services at NRC with the community-based therapeutic care to deliver continuum of care from facility to door step and vice versa. PMID- 26153391 TI - Adaptive Functioning and Feeding Behavior: Key Targets in Autism Management. PMID- 26153392 TI - Fulminant Myocarditis in Children Successfully Treated with High Dose of Methyl Prednisolone. PMID- 26153393 TI - Effects of interleukin-17A on the bioelectric activity of rat atrial myocardium under normal conditions and during gradual stretching. AB - Using microelectrode technique we studied the effects of interleukin-17A on the activity of rat atrial myocardium under normal conditions and after gradual stretching of the tissue. Perfusion with interleukin-17A for 35 min without stretch, led to an increase in APD25, APD50 and APD90. The effect on the frequency and force of the contraction was absent. Stretching during interleukin 17A perfusion led to an increase only at the level of APD90. In the same condition, the repetition frequency of the action potentials did not change as well. Close observation of the cytokine induced mechanisms, confirmed that IL-17A act on different levels and induce different signaling pathways involved in the regulation of cardiac function. PMID- 26153394 TI - Extensive serum biomarker analysis in patients with ST segment elevation myocardial infarction (STEMI). AB - ST segment elevation myocardial infarction (STEMI) is one of the leading causes of morbidity and mortality and some characteristics of STEMI are poorly understood. The aim of the present study is to detect protein expression profiles in the serum of STEMI patients, and to identify biomarkers for this disease. Cytokine profiles of serum from STEMI patients and healthy controls were analyzed with a semi-quantitative human antibody array for 174 proteins, and the results showed blood serum concentrations of 21 cytokines differed considerably between STEMI patients and healthy subjects. In the next phase, a sandwich ELISA kit individually validated eight biomarker results from 21 of the microarray experiments. Clinical validation demonstrated a significant increase of BNDF, PDGF-AA and MMP-9 in patients with AMI. Meanwhile, BNDF, PDGF-AA and MMP-9 distinguished AMI patients from healthy controls with a mean area under the receiver operating characteristic (ROC) curves of 0.870, 0.885, and 0.81, respectively, with diagnostic cut-off points of 0.688 ng/mL, 297.86 ng/mL and 690.066 ng/mL. Our study indicated that these three cytokines were up-regulated in STEMI samples, and may hold promise for the assessment of STEMI. PMID- 26153395 TI - Cortical thickness in Parkinsonians with impulse control disorders: A comment. PMID- 26153396 TI - Comparative Effectiveness of Angiotensin II Receptor Blockers Versus Angiotensin Converting Enzyme Inhibitors Following Contemporary Treatments in Patients with Acute Myocardial Infarction: Results from the Korean Working Group in Myocardial Infarction (KorMI) Registry. AB - BACKGROUND: There are few data on the comparative effectiveness of angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) in a broad spectrum of patients with acute myocardial infarction (AMI), undergoing percutaneous coronary intervention (PCI). METHODS: A total of 8574 patients were selected from the prospective AMI registry, the Korean Working Group in Myocardial Infarction (KorMI) Registry, and divided into two groups on the basis of discharge prescription: ARB (n = 2281) or ACEI (n = 6293). The study was also designed using propensity-score matching (1171 patients in the ARB vs. 2752 patients in the ACEI group). The primary outcome was a composite of cardiac death or myocardial infarction (MI) during 1-year follow-up. RESULTS: The Cox model showed both the ARB and ACEI groups had similar risk of cardiac death or MI [adjusted hazard ratio (HR) for ARB 0.69, 95% confidence interval (CI) 0.38-1.25, p = 0.22]. This result was consistent across various risk subgroups, including patients with preserved left ventricular systolic function, or according to the Global Registry of Acute Coronary Events (GRACE) risk scoring system. After propensity-score matching, there was no significant difference in the incidence of cardiac death or MI between the groups (1.3% in the ARB group vs. 1.7% in the ACEI group, adjusted HR for ARB 0.68, 95% CI 0.38-1.23, p = 0.21). The risks of all-cause death, cardiac death, or MI were also similar between groups. CONCLUSIONS: In a broad spectrum of AMI patients with interventional and pharmacologic treatments, the short-term risk of cardiac death or MI was similar between ARB and ACEI groups. PMID- 26153397 TI - A Method to Combine Signals from Spontaneous Reporting Systems and Observational Healthcare Data to Detect Adverse Drug Reactions. AB - INTRODUCTION: Observational healthcare data contain information useful for hastening detection of adverse drug reactions (ADRs) that may be missed by using data in spontaneous reporting systems (SRSs) alone. There are only several papers describing methods that integrate evidence from healthcare databases and SRSs. We propose a methodology that combines ADR signals from these two sources. OBJECTIVES: The aim of this study was to investigate whether the proposed method would result in more accurate ADR detection than methods using SRSs or healthcare data alone. RESEARCH DESIGN: We applied the method to four clinically serious ADRs, and evaluated it using three experiments that involve combining an SRS with a single facility small-scale electronic health record (EHR), a larger scale network-based EHR, and a much larger scale healthcare claims database. The evaluation used a reference standard comprising 165 positive and 234 negative drug-ADR pairs. MEASURES: Area under the receiver operator characteristics curve (AUC) was computed to measure performance. RESULTS: There was no improvement in the AUC when the SRS and small-scale HER were combined. The AUC of the combined SRS and large-scale EHR was 0.82 whereas it was 0.76 for each of the individual systems. Similarly, the AUC of the combined SRS and claims system was 0.82 whereas it was 0.76 and 0.78, respectively, for the individual systems. CONCLUSIONS: The proposed method resulted in a significant improvement in the accuracy of ADR detection when the resources used for combining had sufficient amounts of data, demonstrating that the method could integrate evidence from multiple sources and serve as a tool in actual pharmacovigilance practice. PMID- 26153398 TI - Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study. AB - INTRODUCTION: Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. METHODS: We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. RESULTS: Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. CONCLUSION: Linkage of primary care or prescription databases to CA registries improved the quality of information on maternal use of medicines in pregnancy, especially for medicine groups that are less fully registered in CA registries. PMID- 26153399 TI - The efficacy of chimeric vaccines constructed with PEP-1 and Ii-Key linking to a hybrid epitope from heterologous viruses. AB - The heterologous epitope-peptide from different viruses may represent an attractive candidate vaccine. In order to evaluate the role of cell-permeable peptide (PEP-1) and Ii-Key moiety from the invariant chain (Ii) of MHC on the heterologous peptide chimeras, we linked the two vehicles to hybrid epitopes on the VP2 protein (aa197-209) of the infectious bursal disease virus and HN protein (aa345-353) of the Newcastle disease virus. The chimeric vaccines were prepared and injected into mice. The immune effects were measured by indirect ELISA. The results showed that the vehicle(s) could significantly boost immune effects against the heterologous epitope peptide. The Ii-Key-only carrier induced more effective immunological responses, compared with the PEP-1 and Ii-Key hybrid vehicle. The carrier-peptide hybrids all showed strong colocalization with major histocompatibility complex (MHC) class II molecules compared with the epitope peptide (weakly-binding) after co-transfection into 293T cells. Together, our results lay the groundwork for designing new hybrid vaccines based on Ii-Key and/or PEP-1 peptides. PMID- 26153400 TI - Different strategies from monotherapies to dual or triple fixed dose combination therapies to achieve blood pressure goals: a summary of a satellite symposium from the European Society of Hypertension. PMID- 26153401 TI - Hypertension in Young People: Epidemiology, Diagnostic Assessment and Therapeutic Approach. AB - High blood pressure (BP) still remains one of the most relevant cardiovascular risk factors, also due to its persistently high prevalence and growing incidence in the general adult and elderly population. Since almost all hypertension related cardiovascular complications, mostly including coronary artery disease, myocardial infarction, ischemic stroke, and congestive heart failure, occurred in adult and elderly individuals, evidence on both prevalence and clinical management of hypertension in young individuals are lacking. Therefore, the clinical impact of high BP levels in young populations remains to be explored. In the recent years, the attitude of the scientific community has changed and more attention was devoted to young individuals with hypertension, also in view of the fact that early identification of these subjects may prevent developing of established hypertension in adulthood. In addition, unhealthy lifestyle habits have progressively involved children and adolescents worldwide, thus contributing to further increase the risk of developing hypertension in young individuals. On the basis of these considerations, the present review is aimed at providing a brief reappraisal of the major aspects of hypertension in the young age, as well as at promoting interest and discussion on this important issue. PMID- 26153402 TI - Opinion: Endogenizing culture in sustainability science research and policy. PMID- 26153404 TI - A Self-Healing Electronic Sensor Based on Thermal-Sensitive Fluids. AB - A combination of liquid sensing materials and self-healing polymers is conceived for preparing electronic sensors that can be mended when they suffer damage. The leakage of ionic liquids at a breaking state is avoided with the help of the capillary effect. Photothermal conversion and magnetic-thermal conversion extend the sensing application. The successful development of self-healing sensors is promising for exploiting high-level electronic devices with long-term service. PMID- 26153405 TI - All Metal Nitrides Solid-State Asymmetric Supercapacitors. AB - Two metal nitrides, TiN porous layers and Fe2 N nanoparticles, are grown uniformly with the assistance of atomic layer deposition on vertically aligned graphene nanosheets and used as the cathode and anode for solid-state supercapacitors, respectively. Full cells are constructed and show good flexibility, high-rate capability, and 98% capacitance retention after 20,000 cycles. PMID- 26153406 TI - A critical role for ATF2 transcription factor in the regulation of E-selectin expression in response to non-endotoxin components of Neisseria meningitidis. AB - Vascular injury is a serious complication of sepsis due to the gram-negative bacterium Neisseria meningitidis. One of the critical early steps in initiating this injury is via the interaction of leucocytes, particularly neutrophils, with adhesion molecules expressed on inflamed endothelium. We have previously demonstrated that both lipopolysaccharide (LPS) and non-LPS components of meningococci can induce very high levels of expression of the vascular endothelial cell adhesion molecule E-selectin, which is critical for early tethering and capture of neutrophils onto endothelium under flow. Using an LPS deficient strain of meningococcus, we showed that very high levels of expression can be induced in primary endothelial cells, even in the context of weak activation of the major host signal transduction factor [nuclear factor-kappaB (NF-kappaB)]. In this study, we show that the particular propensity for N. meningitidis to induce high levels of expression is regulated at a transcriptional level, and demonstrate a significant role for phosphorylation of the ATF2 transcription factor, likely via mitogen-activated protein (MAP) kinases, on the activity of the E-selectin promoter. Furthermore, inhibition of E selectin expression in response to the lpxA- strain by a p38 inhibitor indicates a significant role of a p38-dependent MAPK signalling pathway in ATF2 activation. Collectively, these data highlight the role that LPS and other bacterial components have in modulating endothelial function and their involvement in the pathogenesis of meningococcal sepsis. Better understanding of these multiple mechanisms induced by complex stimuli such as bacteria, and the specific inflammatory pathways they activate, may lead to improved, focused interventions in both meningococcal and potentially bacterial sepsis more generally. PMID- 26153407 TI - Haemophilus influenzae P4 Interacts With Extracellular Matrix Proteins Promoting Adhesion and Serum Resistance. AB - Interaction with the extracellular matrix (ECM) is one of the successful colonization strategies employed by nontypeable Haemophilus influenzae (NTHi). Here we identified Haemophilus lipoprotein e (P4) as a receptor for ECM proteins. Purified recombinant P4 displayed a high binding affinity for laminin (Kd = 9.26 nM) and fibronectin (Kd = 10.19 nM), but slightly less to vitronectin (Kd = 16.51 nM). A P4-deficient NTHi mutant showed a significantly decreased binding to these ECM components. Vitronectin acquisition conferred serum resistance to both P4 expressing NTHi and Escherichia coli transformants. P4-mediated bacterial adherence to pharynx, type II alveolar, and bronchial epithelial cells was mainly attributed to fibronectin. Importantly, a significantly reduced bacterial infection was observed in the middle ear of the Junbo mouse model when NTHi was devoid of P4. In conclusion, our data provide new insight into the role of P4 as an important factor for Haemophilus colonization and subsequent respiratory tract infection. PMID- 26153408 TI - Necrotizing Scleritis, Conjunctivitis, and Other Pathologic Findings in the Left Eye and Brain of an Ebola Virus-Infected Rhesus Macaque (Macaca mulatta) With Apparent Recovery and a Delayed Time of Death. AB - A 3.5-year-old adult female rhesus macaque (Macaca mulatta) manifested swelling of the left upper eyelid and conjunctiva and a decline in clinical condition 18 days following intramuscular challenge with Ebola virus (EBOV; Kikwit-1995), after apparent clinical recovery. Histologic lesions with strong EBOV antigen staining were noted in the left eye (scleritis, conjunctivitis, and peri-optic neuritis), brain (choriomeningoencephalitis), stomach, proximal duodenum, and pancreas. Spleen, liver, and adrenal glands, common targets for acute infection, appeared histologically normal with no evidence of EBOV immunoreactivity. These findings may provide important insight for understanding sequelae seen in West African survivors of Ebola virus disease. PMID- 26153410 TI - Whole-Genome Sequencing During Measles Outbreaks. PMID- 26153409 TI - Whole-Genome Sequencing of Measles Virus Genotypes H1 and D8 During Outbreaks of Infection Following the 2010 Olympic Winter Games Reveals Viral Transmission Routes. AB - We used whole-genome sequencing to investigate a dual-genotype outbreak of measles occurring after the XXI Olympic Winter Games in Vancouver, Canada. By sequencing 27 complete genomes from H1 and D8 genotype measles viruses isolated from outbreak cases, we estimated the virus mutation rate, determined that person to-person transmission is typically associated with 0 mutations between isolates, and established that a single introduction of H1 virus led to the expansion of the outbreak beyond Vancouver. This is the largest measles genomics project to date, revealing novel aspects of measles virus genetics and providing new insights into transmission of this reemerging viral pathogen. PMID- 26153411 TI - Image-guided real-time navigation for transanal total mesorectal excision: a pilot study. AB - BACKGROUND: Frameless stereotaxy for real-time, image-guided surgery has been most utilized for neurological and orthopedic surgery. Recently, our center has reported the application of real-time navigation for transanal total mesorectal excision. METHODS: During a 5-month period (June 2013-October 2013), three male patients underwent transanal minimally invasive surgery for total mesorectal excision with image-guided real-time navigation during the transanal portion of the operation. This was completed using a frameless stereotactic navigational system as shown in a demonstration video. Male patients with anterior, locally advanced rectal cancer were selected for enrollment into the pilot study. RESULTS: Three male patients (mean age 69) underwent transanal total mesorectal excision with stereotactic navigation during a 5-month study period. Mean operative time was 402 min, and there were no intra-operative complications recorded. The mean distance from anal verge of the tumor was 6.3 cm (range 4-8 cm). The navigational accuracy was computed to be +/-3.69 mm (range +/-3.20 to +/ 4.02 mm). The average navigation setup time was 47 min, not including scan time. The surgical specimens were found to have completely intact mesorectal envelopes (Quirke 3) in all cases. All margins, including radial and distal margins, were negative. Mean postoperative length of stay was 5 days. At a median of 18-month follow-up, there was no evidence of locoregional recurrence or distant metastatic disease. CONCLUSION: This is the first pilot series to report the use of frameless stereotactic navigation for TAMIS-TME. Stereotactic navigation for transanal total mesorectal excision is shown to be feasible, and may aid in providing colorectal surgeons with the ability to better perform safe, high quality surgery in select cases. PMID- 26153412 TI - Wrap technique for rectal prolapse: video step by step. PMID- 26153413 TI - Treatment of acute hemorrhoidal crisis using hyaluronidase with local anesthetic prior to surgical excision. PMID- 26153414 TI - Retraction. PMID- 26153415 TI - Stimulus Frequency Otoacoustic Emissions Provide No Evidence for the Role of Efferents in the Enhancement Effect. AB - Auditory enhancement refers to the perceptual phenomenon that a target sound is heard out more readily from a background sound if the background is presented alone first. Here we used stimulus-frequency otoacoustic emissions (SFOAEs) to test the hypothesis that activation of the medial olivocochlear efferent system contributes to auditory enhancement effects. The SFOAEs were used as a tool to measure changes in cochlear responses to a target component and the neighboring components of a multitone background between conditions producing enhancement and conditions producing no enhancement. In the "enhancement" condition, the target and multitone background were preceded by a precursor stimulus with a spectral notch around the signal frequency; in the control (no-enhancement) condition, the target and multitone background were presented without the precursor. In an experiment using a wideband multitone stimulus known to produce significant psychophysical enhancement effects, SFOAEs showed no changes consistent with enhancement, but some aspects of the results indicated possible contamination of the SFOAE magnitudes by the activation of the middle-ear-muscle reflex. The same SFOAE measurements performed using narrower-band stimuli at lower sound levels also showed no SFOAE changes consistent with either absolute or relative enhancement despite robust psychophysical enhancement effects observed in the same listeners with the same stimuli. The results suggest that cochlear efferent control does not play a significant role in auditory enhancement effects. PMID- 26153416 TI - Biocompatibility of magnesium implants in primary human reaming debris-derived cells stem cells in vitro. AB - BACKGROUND: Use of magnesium for resorbable metal implants is a new concept in orthopaedic and dental medicine. The majority of studies on magnesium's biocompatibility in vitro have assessed the short-term effect of magnesium extract on cells. The aim of this study was to evaluate the influence of direct exposure to magnesium alloys on the bioactivity of primary human reaming debris derived (HRD) cells. MATERIALS AND METHODS: Pure Mg, Mg2Ag, WE43 and Mg10Gd were tested for biocompatibility. The study consisted of assessment of cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, evaluation of alkaline phosphatase (ALP) content, and study of cell morphology under light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), along with determination of calcification and pH changes induced by magnesium. RESULTS: The number of viable cells in the presence of Mg2Ag was high over the entire observation period. Inhibition of ALP content in osteogenic differentiating HRD was caused by pure Mg at day 14 and 28. All other magnesium alloys did not affect the ALP content. Exposure of HRD to magnesium increased the amount of lysosomes and endocytotic vesicles. Cellular attachment was generally the best for those crystals that formed on the surface of all materials. A decrease was observed in Ca(2+) in the medium from day 1 to day 14. CONCLUSIONS: In terms of cell morphology, cell viability and differentiation, cell density and the effect on the surrounding pH, Mg2Ag showed the most promising results. All magnesium materials induced calcification, which is beneficial for orthopaedic and dental applications. PMID- 26153417 TI - TCR signaling intensity controls CD8+ T cell responsiveness to TGF-beta. AB - DGK-zeta is a negative regulator of TCR signaling that causes degradation of the second messenger DAG, terminating DAG-mediated activation of Ras and PKCtheta. Cytotoxic T cells deficient in DGK-zeta demonstrate enhanced effector functions in vitro and antitumor activity in vivo, perhaps because of insensitivity to inhibitory cytokines. We sought to determine whether the enhanced responsiveness of DGK-zeta-deficient T cells renders them insensitive to the inhibitory cytokine TGF-beta and to determine how the loss of DGK-zeta facilitates this insensitivity. We identified decreased transcriptional and functional responses to TGF-beta in CD8(+) DGK-zeta(-/-) T cells but preserved TGF-beta-mediated conversion of naive DGK-zeta(-/-) CD4(+) T cells to a regulatory T cell phenotype. Decreased CD8(+) T cell responsiveness to TGF-beta did not result from impaired canonical TGF-beta signal transduction, because similar levels of TGF beta-R and intracellular Smad components were identified in WT and DGK-zeta(-/-) CD8(+) T cells, and TGF-beta-mediated activation of Smad2 was unchanged. Instead, an enhanced TCR signal strength was responsible for TGF-beta insensitivity, because (i) loss of DGK-zeta conferred resistance to TGF-beta-mediated inhibition of Erk phosphorylation, (ii) TGF-beta insensitivity could be recapitulated by exogenous addition of the DAG analog PMA, and (iii) TGF-beta sensitivity could be observed in DGK-zeta-deficient T cells at limiting dilutions of TCR stimulation. These data indicate that enhanced TCR signal transduction in the absence of DGK zeta makes T cells relatively insensitive to TGF-beta, in a manner independent of Smads, a finding with practical implications in the development of immunotherapies that target TGF-beta. PMID- 26153418 TI - Predicting hospital costs for patients receiving renal replacement therapy to inform an economic evaluation. AB - OBJECTIVE: To develop a model to predict annual hospital costs for patients with established renal failure, taking into account the effect of patient and treatment characteristics of potential relevance for conducting an economic evaluation, such as age, comorbidities and time on treatment. The analysis focuses on factors leading to variations in inpatient and outpatient costs and excludes fixed costs associated with dialysis, transplant surgery and high cost drugs. METHODS: Annual costs of inpatient and outpatient hospital episodes for patients starting renal replacement therapy in England were obtained from a large retrospective dataset. Multiple imputation was performed to estimate missing costs due to administrative censoring. Two-part models were developed using logistic regression to first predict the probability of incurring any hospital costs before fitting generalised linear models to estimate the level of cost in patients with positive costs. Separate models were developed to predict inpatient and outpatient costs for each treatment modality. RESULTS: Data on hospital costs were available for 15,869 incident dialysis patients and 4511 incident transplant patients. The two-part models showed a decreasing trend in costs with increasing number of years on treatment, with the exception of dialysis outpatient costs. Age did not have a consistent effect on hospital costs; however, comorbidities such as diabetes and peripheral vascular disease were strong predictors of higher hospital costs in all four models. CONCLUSION: Analysis of patient-level data can result in a deeper understanding of factors associated with variations in hospital costs and can improve the accuracy with which costs are estimated in the context of economic evaluations. PMID- 26153419 TI - Recombinant transfer in the basic genome of Escherichia coli. AB - An approximation to the ~4-Mbp basic genome shared by 32 strains of Escherichia coli representing six evolutionary groups has been derived and analyzed computationally. A multiple alignment of the 32 complete genome sequences was filtered to remove mobile elements and identify the most reliable ~90% of the aligned length of each of the resulting 496 basic-genome pairs. Patterns of single base-pair mutations (SNPs) in aligned pairs distinguish clonally inherited regions from regions where either genome has acquired DNA fragments from diverged genomes by homologous recombination since their last common ancestor. Such recombinant transfer is pervasive across the basic genome, mostly between genomes in the same evolutionary group, and generates many unique mosaic patterns. The six least-diverged genome pairs have one or two recombinant transfers of length ~40-115 kbp (and few if any other transfers), each containing one or more gene clusters known to confer strong selective advantage in some environments. Moderately diverged genome pairs (0.4-1% SNPs) show mosaic patterns of interspersed clonal and recombinant regions of varying lengths throughout the basic genome, whereas more highly diverged pairs within an evolutionary group or pairs between evolutionary groups having >1.3% SNPs have few clonal matches longer than a few kilobase pairs. Many recombinant transfers appear to incorporate fragments of the entering DNA produced by restriction systems of the recipient cell. A simple computational model can closely fit the data. Most recombinant transfers seem likely to be due to generalized transduction by coevolving populations of phages, which could efficiently distribute variability throughout bacterial genomes. PMID- 26153420 TI - Vascular disease-causing mutation R258C in ACTA2 disrupts actin dynamics and interaction with myosin. AB - Point mutations in vascular smooth muscle alpha-actin (SM alpha-actin), encoded by the gene ACTA2, are the most prevalent cause of familial thoracic aortic aneurysms and dissections (TAAD). Here, we provide the first molecular characterization, to our knowledge, of the effect of the R258C mutation in SM alpha-actin, expressed with the baculovirus system. Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region. Both aspects of R258C function therefore need investigation. Total internal reflection fluorescence (TIRF) microscopy was used to quantify the growth of single actin filaments as a function of time. R258C filaments are less stable than WT and more susceptible to severing by cofilin. Smooth muscle tropomyosin offers little protection from cofilin cleavage, unlike its effect on WT actin. Unexpectedly, profilin binds tighter to the R258C monomer, which will increase the pool of globular actin (G-actin). In an in vitro motility assay, smooth muscle myosin moves R258C filaments more slowly than WT, and the slowing is exacerbated by smooth muscle tropomyosin. Under loaded conditions, small ensembles of myosin are unable to produce force on R258C actin-tropomyosin filaments, suggesting that tropomyosin occupies an inhibitory position on actin. Many of the observed defects cannot be explained by a direct interaction with the mutated residue, and thus the mutation allosterically affects multiple regions of the monomer. Our results align with the hypothesis that defective contractile function contributes to the pathogenesis of TAAD. PMID- 26153421 TI - Jagged mediates differences in normal and tumor angiogenesis by affecting tip stalk fate decision. AB - Angiogenesis is critical during development, wound repair, and cancer progression. During angiogenesis, some endothelial cells adopt a tip phenotype to lead the formation of new branching vessels; the trailing stalk cells proliferate to develop the vessel. Notch and VEGF signaling mediate the selection of these tip endothelial cells. However, how Jagged, a Notch ligand that is overexpressed in cancer, affects angiogenesis remains elusive. Here, by developing a theoretical framework for Notch-Delta-Jagged-VEGF signaling, we found that higher production levels of Jagged destabilizes the tip and stalk cell fates and can give rise to a hybrid tip/stalk phenotype that leads to poorly perfused and chaotic angiogenesis, which is a hallmark of cancer. Consistently, the signaling interactions that restrict Notch-Jagged signaling, such as Fringe, cis inhibition, and increased production of Delta, stabilize tip and stalk fates and limit the existence of hybrid tip/stalk phenotype. Our results underline how overexpression of Jagged can transform physiological angiogenesis into pathological one. PMID- 26153422 TI - KTKEGV repeat motifs are key mediators of normal alpha-synuclein tetramerization: Their mutation causes excess monomers and neurotoxicity. AB - alpha-Synuclein (alphaS) is a highly abundant neuronal protein that aggregates into beta-sheet-rich inclusions in Parkinson's disease (PD). alphaS was long thought to occur as a natively unfolded monomer, but recent work suggests it also occurs normally in alpha-helix-rich tetramers and related multimers. To elucidate the fundamental relationship between alphaS multimers and monomers in living neurons, we performed systematic mutagenesis to abolish self-interactions and learn which structural determinants underlie native multimerization. Unexpectedly, tetramers/multimers still formed in cells expressing each of 14 sequential 10-residue deletions across the 140-residue polypeptide. We postulated compensatory effects among the six highly conserved and one to three additional alphaS repeat motifs (consensus: KTKEGV), consistent with alphaS and its homologs beta- and gamma-synuclein all forming tetramers while sharing only the repeats. Upon inserting in-register missense mutations into six or more alphaS repeats, certain mutations abolished tetramer formation, shown by intact-cell cross linking and independently by fluorescent-protein complementation. For example, altered repeat motifs KLKEGV, KTKKGV, KTKEIV, or KTKEGW did not support tetramerization, indicating the importance of charged or small residues. When we expressed numerous different in-register repeat mutants in human neural cells, all multimer-abolishing but no multimer-neutral mutants caused frank neurotoxicity akin to the proapoptotic protein Bax. The multimer-abolishing variants became enriched in buffer-insoluble cell fractions and formed round cytoplasmic inclusions in primary cortical neurons. We conclude that the alphaS repeat motifs mediate physiological tetramerization, and perturbing them causes PD-like neurotoxicity. Moreover, the mutants we describe are valuable tools for studying normal and pathological properties of alphaS and screening for tetramer stabilizing therapeutics. PMID- 26153423 TI - Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis. AB - Homozygous cardiac myosin binding protein C-deficient (Mybpc(t/t)) mice develop dramatic cardiac dilation shortly after birth; heart size increases almost twofold. We have investigated the mechanism of cardiac enlargement in these hearts. Throughout embryogenesis myocytes undergo cell division while maintaining the capacity to pump blood by rapidly disassembling and reforming myofibrillar components of the sarcomere throughout cell cycle progression. Shortly after birth, myocyte cell division ceases. Cardiac MYBPC is a thick filament protein that regulates sarcomere organization and rigidity. We demonstrate that many Mybpc(t/t) myocytes undergo an additional round of cell division within 10 d postbirth compared with their wild-type counterparts, leading to increased numbers of mononuclear myocytes. Short-hairpin RNA knockdown of Mybpc3 mRNA in wild-type mice similarly extended the postnatal window of myocyte proliferation. However, adult Mybpc(t/t) myocytes are unable to fully regenerate the myocardium after injury. MYBPC has unexpected inhibitory functions during postnatal myocyte cytokinesis and cell cycle progression. We suggest that human patients with homozygous MYBPC3-null mutations develop dilated cardiomyopathy, coupled with myocyte hyperplasia (increased cell number), as observed in Mybpc(t/t) mice. Human patients, with heterozygous truncating MYBPC3 mutations, like mice with similar mutations, have hypertrophic cardiomyopathy. However, the mechanism leading to hypertrophic cardiomyopathy in heterozygous MYBPC3(+/-) individuals is myocyte hypertrophy (increased cell size), whereas the mechanism leading to cardiac dilation in homozygous Mybpc3(-/-) mice is primarily myocyte hyperplasia. PMID- 26153424 TI - Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia. AB - Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT) treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH. PMID- 26153426 TI - Design and validation of a biomechanical bioreactor for cartilage tissue culture. AB - Specific tissues, such as cartilage, undergo mechanical solicitation under their normal performance in human body. In this sense, it seems necessary that proper tissue engineering strategies of these tissues should incorporate mechanical solicitations during cell culture, in order to properly evaluate the influence of the mechanical stimulus. This work reports on a user-friendly bioreactor suitable for applying controlled mechanical stimulation--amplitude and frequency--to three dimensional scaffolds. Its design and main components are described, as well as its operation characteristics. The modular design allows easy cleaning and operating under laminar hood. Different protocols for the sterilization of the hermetic enclosure are tested and ensure lack of observable contaminations, complying with the requirements to be used for cell culture. The cell viability study was performed with KUM5 cells. PMID- 26153425 TI - Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart. AB - Myocardial mitochondrial Ca(2+) entry enables physiological stress responses but in excess promotes injury and death. However, tissue-specific in vivo systems for testing the role of mitochondrial Ca(2+) are lacking. We developed a mouse model with myocardial delimited transgenic expression of a dominant negative (DN) form of the mitochondrial Ca(2+) uniporter (MCU). DN-MCU mice lack MCU-mediated mitochondrial Ca(2+) entry in myocardium, but, surprisingly, isolated perfused hearts exhibited higher O2 consumption rates (OCR) and impaired pacing induced mechanical performance compared with wild-type (WT) littermate controls. In contrast, OCR in DN-MCU-permeabilized myocardial fibers or isolated mitochondria in low Ca(2+) were not increased compared with WT, suggesting that DN-MCU expression increased OCR by enhanced energetic demands related to extramitochondrial Ca(2+) homeostasis. Consistent with this, we found that DN-MCU ventricular cardiomyocytes exhibited elevated cytoplasmic [Ca(2+)] that was partially reversed by ATP dialysis, suggesting that metabolic defects arising from loss of MCU function impaired physiological intracellular Ca(2+) homeostasis. Mitochondrial Ca(2+) overload is thought to dissipate the inner mitochondrial membrane potential (DeltaPsim) and enhance formation of reactive oxygen species (ROS) as a consequence of ischemia-reperfusion injury. Our data show that DN-MCU hearts had preserved DeltaPsim and reduced ROS during ischemia reperfusion but were not protected from myocardial death compared with WT. Taken together, our findings show that chronic myocardial MCU inhibition leads to previously unanticipated compensatory changes that affect cytoplasmic Ca(2+) homeostasis, reprogram transcription, increase OCR, reduce performance, and prevent anticipated therapeutic responses to ischemia-reperfusion injury. PMID- 26153427 TI - Responder to BNP-guided treatment in heart failure. The process of defining a responder. AB - OBJECTIVES: B-type natriuretic peptide (BNP) levels predict prognosis and outcome in heart failure (HF) patients. To evaluate the optimal cut-off level of BNP to predict death, need for hospitalization, and worsening HF, and also to determine the optimal time to apply the chosen cut-off value. DESIGN: In a sub-study from the Use of PeptideS in Tailoring hEart failure Project or UPSTEP study where tailoring treatment of HF by BNP level was evaluated, we assessed the change in percentage between levels of BNP at study start versus a specific week (2, 6, 10, 16, 24, 36, or 48) during the follow-up period. RESULTS: The optimum cut-off percentage levels were obtained using a Cox proportional regression analysis of death, hospitalization, and worsening HF. A decrease in BNP by less than 40% in week 16 compared with study start and/or a BNP > 300 ng/L presented the highest hazard ratio (HR) for a non-responder to reach a combined endpoint (HR: 2.43; 95% confidence interval or CI: 1.61-3.65; p < 0.00003). This definition gave a 78% risk reduction of cardiovascular (CV) mortality (p > 0.0005) and an 89% risk reduction of HF mortality (p > 0.004), and reduced risk of CV and HF hospitalization for the responders. CONCLUSIONS: Patients with a decrease in BNP of more than 40% compared with that at study start and/or a BNP level below 300 ng/L at week 16 had a significantly reduced risk of CV and HF mortality and hospitalization. PMID- 26153429 TI - Association between arsenic exposure and thyroid function: data from NHANES 2007 2010. AB - The association of arsenic variables in urine, total arsenic (UAS), arsenobetaine (UAB), dimethylarsinic acid (UDMA), and arsenic adjusted for arsenobetaine (UAAS) with thyroid-stimulating hormone (TSH), free and total serum thyroxine (FT4, TT4), free and total triiodothyronine (FT3, TT3), and thyroglobulin (TGN) was evaluated by analyzing data from 2007-2010 National Health and Nutrition Examination Survey. For iodine deficient males, there was a positive association between TSH and UDMA (p < 0.01) and a negative association between the levels of TT4 and UDMA (p < 0.01). Levels of UAAS were inversely associated with the levels of TT4 for both iodine-deficient (p = 0.054) and iodine-replete females (p < 0.01). For iodine-replete females, levels of both TSH and TGN increased with decrease in the levels of both UAB (p < 0.01) and UAS (p < 0.01). There was also a negative association between TSH and UAB as well as UAS (p < 0.01). For iodine replete males, increased levels of UDMA were associated with decreasing levels of FT4 (p = 0.03). PMID- 26153428 TI - Clonality as a driver of spatial genetic structure in populations of clonal tree species. AB - Random genetic drift, natural selection and restricted gene dispersal are basic factors of the spatial genetic structure (SGS) in plant populations. Clonal reproduction has a profound effect on population dynamics and genetic structure and thus emerges as a potential factor in contributing to and modelling SGS. In order to assess the impact of clonality on SGS we studied clonal structure and SGS in the population of Populus alba. Six hundred and seventy-two individuals were mapped and genotyped with 16 nuclear microsatellite markers. To answer the more general question regarding the relationship between SGS and clonality we used Sp statistics, which allows for comparisons of the extent of SGS among different studies, and the comparison of published data on SGS in clonal and non clonal tree species. Sp statistic was extracted for 14 clonal and 27 non-clonal species belonging to 7 and 18 botanical families, respectively. Results of genetic investigations conducted in the population of P. alba showed over domination of clonal reproduction, which resulted in very low clonal diversity (R = 0.12). Significant SGS was found at both ramet (Sp = 0.095) and genet level (Sp = 0.05) and clonal reproduction was indicated as an important but not sole driving factor of SGS. Within-population structure, probably due to family structure also contributed to high SGS. High mean dominance index (D = 0.82) indicated low intermingling among genets. Literature survey revealed that clonal tree species significantly differ from non-clonal species with respect to SGS, having 2.8-fold higher SGS. This led us to conclude that clonality is a life history trait that can have deep impact on processes acting in populations of clonal tree species leading to significant SGS. PMID- 26153431 TI - Evidence-based medicine: what does the future hold? PMID- 26153430 TI - A simplified protocol for the isolation and culture of cardiomyocytes and progenitor cells from neonatal mouse ventricles. AB - The neonatal heart is a very useful tool for the study of biochemical pathways and properties of cardiomyocytes and as it has the potential to regenerate for a brief period of time from birth; it is also useful to study cardiac regeneration. However, as the heart matures, this proficiency for regeneration is reduced. This regenerative potential may be influenced by the microenvironment of the heart in the early stages of postnatal development and therefore, cell cultures derived at this stage may contain functional cardiomyocytes and progenitor cells. The aim of this study was to identify key steps in the isolation and culture of such early stage-neonatal mouse hearts to allow maximum migration of cardiomyocytes from the explant and their maintenance as functional, long term cultures. Explant cultures of mouse ventricles preserved 3-dimensional structure and generated migrating layers of cardiomyocytes that expressed alpha sarcomeric actin which could be further sub-cultured by enzymatic dissociation. Western blotting demonstrated expression of c-KIT, GATA4, alpha sarcomeric actin and connexin43 proteins after 20 days of explant culture. ACTA1, GATA4, and CX43 continued to express in five weeks old explant cultures while the c-KIT protein was expressed up to two passages during sub-culture. Real time PCR and SQRT PCR also demonstrated gene expression of cardiomyocyte markers in long term cultures. Migrating cells from the explants assembled into contracting spheroids after subculture and expressed the c-KIT protein. Progenitor markers CD44, CD90, and extracellular proteins, periostin and vimentin demonstrated the preservation of cellular heterogeneity in such cultures. Supplementation with Hydrocortisone maintained a cardioprotective environment and reduced the non-myocyte population. This is an optimized and efficient method for the generation of neonatal heart cultures that is not labor intensive and does not require supplementation with cytokines. PMID- 26153432 TI - The relationships of eccentric strength and power with dynamic balance in male footballers. AB - Unilateral balance is critical to kicking accuracy in football. In order to design interventions to improve dynamic balance, knowledge of the relationships between dynamic balance and specific neuromuscular factors such as eccentric strength and power is essential. Therefore, the aim was to determine the relationships of eccentric strength and power with dynamic balance in male footballers. The Y-balance test, eccentric isokinetic strength testing (knee extensors and flexors) and the countermovement jump were assessed in fifty male footballers (university (n = 27, mean age = 20.7 +/- 1.84 years) and professional (n = 23, mean age = 23.0 +/- 3.08 years). Spearman Rank Order correlations were used to determine the relationships of eccentric strength and power with dynamic balance. Multiple linear regression, adjusting for age, mass, stature, playing experience and competitive level was performed on significant relationships. Normalised reach score in the Y-balance test using the non-dominant leg for stance correlated with (1) eccentric strength of the non-dominant leg knee extensors in the university group (r = 0.50, P = 0.008) and (2) countermovement jump height in the university (r = 0.40, P = 0.04) and professional (r = 0.56, P = 0.006) football groups, respectively. No relationships were observed between eccentric strength (knee flexors) and normalised reach scores. Despite the addition of potential confounders, the relationship of power and dynamic balance was significant (r = 0.52, P < 0.0002). The ability to generate power correlates moderately with dynamic balance on the non-dominant leg in male footballers. PMID- 26153433 TI - Adolescent elite Kenyan runners are at risk for energy deficiency, menstrual dysfunction and disordered eating. AB - Limited data are available on the female athlete triad (Triad) in athletes from minority groups. We explored subclinical and clinical Triad components amongst adolescent elite Kenyan athletes (n = 61) and non-athletes (n = 49). Participants completed demographic, health, sport and menstrual history questionnaires as well as a 5-day weighed dietary record and exercise log to calculate energy availability (EA). Ultrasound assessed calcaneus bone mineral density (BMD). Eating Disorder Inventory subscales and the Three-Factor Eating Questionnaire's cognitive dietary restraint subscale measured disordered eating (DE). EA was lower in athletes than non-athletes (36.5 +/- 4.5 vs. 39.5 +/- 5.7 kcal ? kg FFM( 1) ? d(-1), P = 0.003). More athletes were identified with clinical low EA (17.9% vs. 2.2%, OR = 9.5, 95% CI 1.17-77, P = 0.021) and clinical menstrual dysfunction (32.7% vs. 18.3%, chi(2) = 7.1, P = 0.02). Subclinical (75.4% vs. 71.4%) and clinical DE (4.9% vs. 10.2%, P = 0.56) as well as BMD were similar between athletes and non-athletes. More athletes had two Triad components than non athletes (8.9% vs. 0%, OR = 0.6, 95% CI 0.5-6.9, P = 0.05). Kenyan adolescent participants presented with one or more subclinical and/or clinical Triad component. It is essential that athletes and their entourage be educated on their energy needs including health and performance consequences of an energy deficiency. PMID- 26153434 TI - Deciding when to stop: efficient experimentation to learn to predict drug-target interactions. AB - BACKGROUND: Active learning is a powerful tool for guiding an experimentation process. Instead of doing all possible experiments in a given domain, active learning can be used to pick the experiments that will add the most knowledge to the current model. Especially, for drug discovery and development, active learning has been shown to reduce the number of experiments needed to obtain high confidence predictions. However, in practice, it is crucial to have a method to evaluate the quality of the current predictions and decide when to stop the experimentation process. Only by applying reliable stopping criteria to active learning can time and costs in the experimental process actually be saved. RESULTS: We compute active learning traces on simulated drug-target matrices in order to determine a regression model for the accuracy of the active learner. By analyzing the performance of the regression model on simulated data, we design stopping criteria for previously unseen experimental matrices. We demonstrate on four previously characterized drug effect data sets that applying the stopping criteria can result in upto 40 % savings of the total experiments for highly accurate predictions. CONCLUSIONS: We show that active learning accuracy can be predicted using simulated data and results in substantial savings in the number of experiments required to make accurate drug-target predictions. PMID- 26153435 TI - Environmental indicators for sustainability: a strategic analysis for the sugarcane ethanol context in Brazil. AB - Sugarcane ethanol is considered a renewable energy source and has emerged as a potential alternative to reduce dependency on fossil fuels, particularly in Brazil. However, there are some questions about how sustainable this energy source is, given the impacts from its production and use on a larger scale. To understand and achieve sustainability, it is essential to build tools that can assess an integrated conception and help decision-makers to establish public policies for a sustainable development. The indicators appear as such tools by capturing the complexity without reducing the significance of each system's component. The environmental indicators such as water quality indicator represent the level of water pollution, considering several parameters. The importance of the development, selection and validation of environmental indicators through a structured and cohesive process becomes essential. In the State of Sao Paulo, in Brazil, the environmental indicators, as well as policies based on them, are defined by the Environmental Secretariat (SMA/SP). This article presents an environmental indicator's evaluation method and reports based on the discussions about sustainability for the ethanol sugarcane context in the State of Sao Paulo. The method consists of interviews and an expert's workshop which pointed out a set of benchmarks for the evaluation of environmental indicators. The procedures were applied to an indicator used by the SMA/SP to illustrate the method's effectiveness. The results show that a strategic analysis framework can improve the environmental indicators required for the discussion on sustainability, providing a better guide to decision-makers. PMID- 26153436 TI - A review of epidemiologic studies of low-level exposures to organophosphorus insecticides in non-occupational populations. AB - This paper systematically reviews epidemiologic studies related to low-level non occupational exposures to organophosphorus (OP) insecticides. Many of the studies evaluate levels of maternal OP metabolites and subsequent health outcomes in offspring. The studies focused primarily on birth outcomes (e.g., infant body weight or head circumference) and neurodevelopmental (e.g., mental and psychomotor) testing results. The evidence from these studies was reviewed under the Bradford Hill guidelines. Most of the studies assessing exposure based on urinary levels of OP insecticide metabolites used only one or two measurements during pregnancy. The potential for exposure misclassification with this method is largely due to (1) preformed metabolites that are ingested with food, (2) the short elimination half-life of OP insecticides, and (3) lack of specificity to particular OP insecticides for many of the metabolites. For birth outcomes, the majority of reported results are not statistically significant, and the associations are inconsistent within and across studies. There is more within study consistency for some of the neurodevelopmental testing results, although few associations were examined across several studies. These associations are generally weak, have been replicated only to a limited extent, and require further confirmation before they can be considered established. The OP insecticide levels measured in the epidemiologic studies are too low to cause biologically meaningful acetylcholinesterase inhibition, the most widely used metric for OP insecticide toxicity. Overall, the available evidence does not establish that low-level exposures to OP insecticides cause adverse birth outcomes or neurodevelopmental problems in humans. PMID- 26153437 TI - Genetic divergence and phylogeographic history of two closely related species (Leucomeris decora and Nouelia insignis) across the 'Tanaka Line' in Southwest China. AB - BACKGROUND: Leucomeris decora and Nouelia insignis (Asteraceae) are narrowly and allopatrically distributed species, separated by the important biogeographic boundary Tanaka Line in Southwest China. Previous morphological, cytogenetic and molecular studies suggested that L. decora is sister to N. insignis. However, it is less clear how the two species diverged, whether in full isolation or occurring gene flow across the Tanaka Line. Here, we performed a molecular study at the population level to characterize genetic differentiation and decipher phylogeographic history in two closely related species based on variation examined in plastid and nuclear DNAs using a coalescent-based approach. RESULTS: These morphologically distinct species share plastid DNA (cpDNA) haplotypes. In contrast, Bayesian analysis of nuclear DNA (nDNA) uncovered two distinct clusters corresponding to L. decora and N. insignis. Based on the IMa analysis, no strong indication of migration was detected based on both cpDNA and nDNA sequences. The molecular data pointed to a major west-east split in nuclear DNA between the two species corresponding with the Tanaka Line. The coalescent time estimate for all cpDNA haplotypes dated to the Mid-Late Pleistocene. The estimated demographic parameters showed that the population size of L. decora was similar to that of N. insignis and both experienced limited demographic fluctuations recently. CONCLUSIONS: The study revealed comprehensive species divergence and phylogeographic histories of N. insignis and L. decora divided by the Tanaka Line. The phylogeographic pattern inferred from cpDNA reflected ancestrally shared polymorphisms without post-divergence gene flow between species. The marked genealogical lineage divergence in nDNA provided some indication of Tanaka Line for its role as a barrier to plant dispersal, and lent support to its importance in promoting strong population structure and allopatric divergence. PMID- 26153439 TI - Ephedra water decoction and cough tablets containing ephedra and liquorice induce CYP1A2 but not CYP2E1 hepatic enzymes in rats. AB - 1. Ephedra water decoction (EWD) and cough tablets containing ephedra and liquorice (maxing cough tablets, MXCT) have been widely used in the treatment of asthma. In the clinic, EWD and MXCT may be prescribed with theophylline, one of the most popular antiasthmatic drugs. CYP1A2 and CYP2E1 are mainly involved in the oxidative metabolism of theophylline in human liver. Drug interactions involving the cytochrome P450 (CYP) isoforms generally are of two types: enzyme induction or enzyme inhibition. Enzyme inhibition reduces metabolism, whereas induction can increase it. 2. To evaluate the pretreatment effect of EWD and MXCT on CYP1A2 and CYP2E1, CYP1A2 and CYP2E1 activity, the protein expression and mRNA expression levels were determined. After pretreatment with EWD or MXCT, the enzyme activity, mRNA expression and protein expression of CYP1A2 were increased significantly (p < 0.05), but enzyme activity of CYP2E1 did not change compared with the control. 3. It was demonstrated that EWD or MXCT pretreatment obviously induced CYP1A2, therefore, in patients taking EWD or MXCT, possible CYP-induced drug interaction should be noted to decrease the risk of therapeutic failure or adverse effects resulting from the use of additional therapeutic agents. PMID- 26153440 TI - Metabolism of drugs and other xenobiotics in giant liver fluke (Fascioloides magna). AB - 1. Giant liver fluke Fascioloides magna is a dangerous parasite, which infects herbivores. It was imported to Europe from North America and started to spread. Benzimidazoles like albendazole, mebendazole, triclabendazole and salicylanilides closantel and rafoxanide are the most used anthelmintics to control fascioloidosis. However their effect might be altered via drug-metabolizing enzymes of this parasite. 2. The aim of our study was to determine the activities of drug-metabolizing enzymes in F. magna and the metabolism of above mentioned anthelmintics. 3. Activities of several oxidative, reductive and conjugative enzymes towards various model xenobiotic substrates were found in F. magna subcellular fractions. 4. Subcellular fractions from F. magna oxidized albendazole to its sulphoxide metabolite and reduced mebendazole to hydroxyl mebendazole. Under ex vivo conditions, only very-low concentrations of these compounds were detected using high-performance liquid chromatography/mass spectrometry. 5. The results indicate that the giant liver fluke possesses the active xenobiotic-metabolizing system. The overexpression of this system may play an important role in parasite resistance against these anthelmintics. PMID- 26153441 TI - Route of administration and formulation dependent pharmacokinetics of 17 hydroxyprogesterone caproate in rats. AB - 1. Weekly intramuscular injections of (250 mg/week) of 17-hydroxyprogesterone caproate (17-OHPC) are the only treatment option for prevention of preterm birth in women with a prior history of preterm delivery. 2. The objective of the current study was to evaluate the use of an alternate formulation and the feasibility of an alternate route of administration of this agent. 17-OHPC was administered to adult female SD rats, as marketed oily formulation intramuscularly, or as a solution IV, IM, or PO. 3. Plasma concentrations of 17 OHPC were measured by LC-MS-MS and pharmacokinetic parameters were calculated by non-compartmental analysis, using WinNonLin (Certara, St. Louis, MO). 4. After IV or IM administration as a solution, the mean half-life of 17-OHPC was around 11 h. The bioavailability was nearly 100% after IM administration, but was very low (<3%) after PO administration of a solution dosage form. 5. Intramuscular injection of the oily formulation resulted in low levels of 17-OHPC that were sustained for a prolonged time period with a projected bioavailability close to 100%. 6. The pharmacokinetics of 17-OHPC is dependent on the formulation and the route of administration. 7. The low bioavailability after oral administration indicates that oral administration of 17-OHPC may not be feasible with simple formulations of this drug. PMID- 26153442 TI - In vitro functional analysis of 24 novel CYP2C19 variants recently found in the Chinese Han population. AB - 1. CYP2C19 is a highly polymorphic enzyme responsible for the metabolism of a wide range of clinical drugs. Alterations to the CYP2C19 gene contribute to the variability of CYP2C19 enzyme activity, which causes pharmacokinetics and drug efficacies to vary and adverse drug reactions to occur in different persons. Recently, we identified 24 novel CYP2C19 allelic variants in the Chinese Han population. The purpose of present study is to assess the impact of these newly found nucleotide mutations on the enzymatic activity of the CYP2C19 protein. 2. Dual-expression vectors were constructed and transiently transfected into 293FT cells. Forty-eight hours after transfection, cells were re-suspended and incubated with two typical probe substrates, omeprazole and S-mephenytoin, to determine the activities of each variant relative to the wild-type protein. 3. Immunoblotting results showed that the protein expression levels of the CYP2C19 variants were diverse. Enzymatic ability analysis showed that the variant 35FS exhibited no functional activity, and most of the other variants showed significantly decreased metabolic activities toward both omeprazole and S mephenytoin compared with wild-type. 4. These findings greatly enrich the knowledge of biological effects of these newly found CYP2C19 mutations and aid the application of this knowledge to future individualized drug therapy in clinic. PMID- 26153443 TI - Characterization of ADME properties of [(14)C]asunaprevir (BMS-650032) in humans. AB - 1. Asunaprevir (ASV, BMS-650032), a highly selective and potent NS3 protease inhibitor, is currently under development for the treatment of chronic hepatic C virus infection. This study describes in vivo biotransformation in humans and the identification of metabolic enzymes of ASV. 2. Following a single oral dose of [(14)C]ASV to humans, the majority of radioactivity (>73% of the dose) was excreted in feces with <1% of the dose recovered in urine. Drug-related radioactivity readily appeared in circulation and the plasma radioactivity was mainly attributed to ASV. A few minor metabolites were observed in human plasma and are not expected to contribute to the pharmacological activity because of low levels. The area under the curve (AUC) values of each circulating metabolite in humans were well below their levels in animals used in the long-term toxicological studies. In bile and feces, intact ASV was a prominent radioactive peak suggesting that both metabolism and direct excretion played important roles in ASV clearance. 3. The primary metabolic pathways of ASV were hydroxylation, sulfonamide hydrolysis and the loss of isoquinoline. In vitro studies with human cDNA expressed CYP enzymes and with human liver microsomes (HLM) in the presence of selective chemical inhibitors demonstrated that ASV was primarily catalyzed by CYP3A4 and CYP3A5. PMID- 26153444 TI - Characterization of ligand-dependent activation of bovine and pig constitutive androstane (CAR) and pregnane X receptors (PXR) with interspecies comparisons. AB - 1. Nuclear receptors CAR (NR1I3) and PXR (NR1I2) are major ligand-activated transcriptional regulators of xenobiotic metabolism and disposition and modulators of endobiotic metabolism. Differences in xenobiotic selectivity between the human and rodent receptors are well recognized but there is lack of such information on properties of CAR and PXR in important domestic animals. 2. The pig and bovine receptors were cloned and their ligand profiles were systematically compared to corresponding human and mouse forms utilizing a panel of xenobiotics and structural analysis. 3. Pig CAR and PXR resemble their human counterparts which can be rationalized by only modest amino acid changes between critical residues of the human ligand-binding pockets (H203Q for CAR, L210V and M243I for PXR). 4. In contrast, bovine CAR shows a blunted response to CAR agonists and inverse agonists. These changes are likely due to disruptive mutations at or near critical hydrogen bond-forming residues (N165I, Y326F). The unresponsiveness of bovine PXR to human- and mouse-selective agonists may be related to substitutions at important ligand-contacting residues R410Q and F305V, respectively. 5. Our findings have implications for regulation of drug metabolizing enzymes and transporters and pharmacokinetics in cattle and pigs. PMID- 26153446 TI - Analysis of ancient human mitochondrial DNA from the Xiaohe cemetery: insights into prehistoric population movements in the Tarim Basin, China. AB - BACKGROUND: The Tarim Basin in western China, known for its amazingly well preserved mummies, has been for thousands of years an important crossroad between the eastern and western parts of Eurasia. Despite its key position in communications and migration, and highly diverse peoples, languages and cultures, its prehistory is poorly understood. To shed light on the origin of the populations of the Tarim Basin, we analysed mitochondrial DNA polymorphisms in human skeletal remains excavated from the Xiaohe cemetery, used by the local community between 4000 and 3500 years before present, and possibly representing some of the earliest settlers. RESULTS: Xiaohe people carried a wide variety of maternal lineages, including West Eurasian lineages H, K, U5, U7, U2e, T, R*, East Eurasian lineages B, C4, C5, D, G2a and Indian lineage M5. CONCLUSION: Our results indicate that the people of the Tarim Basin had a diverse maternal ancestry, with origins in Europe, central/eastern Siberia and southern/western Asia. These findings, together with information on the cultural context of the Xiaohe cemetery, can be used to test contrasting hypotheses of route of settlement into the Tarim Basin. PMID- 26153448 TI - Pulmonary artery dissection in a patient with undiagnosed pulmonary hypertension- A case report and review of literature. AB - Pulmonary artery dissection is rare and highly lethal and most reports in the literature are from autopsies. We describe a patient with undiagnosed primary pulmonary hypertension suffering from pulmonary artery dissection that subsequently underwent surgical repair and in addition review the current literature on this topic. PMID- 26153447 TI - Regulation of synaptic MAPK/ERK phosphorylation in the rat striatum and medial prefrontal cortex by dopamine and muscarinic acetylcholine receptors. AB - Dopamine and acetylcholine are two principal transmitters in the striatum and are usually balanced to modulate local neural activity and to maintain striatal homeostasis. This study investigates the role of dopamine and muscarinic acetylcholine receptors in the regulation of a central signaling protein, i.e., the mitogen-activated protein kinase (MAPK). We focus on the synaptic pool of MAPKs because of the fact that these kinases reside in peripheral synaptic structures in addition to their somatic locations. We show that a systemic injection of dopamine D1 receptor (D1R) agonist SKF81297 enhances phosphorylation of extracellular signal-regulated kinases (ERKs), a prototypic subclass of MAPKs, in the adult rat striatum. Similar results were observed in another dopamine responsive region, the medial prefrontal cortex (mPFC). The dopamine D2 receptor agonist quinpirole had no such effects. Pretreatment with a positive allosteric modulator (PAM) of muscarinic acetylcholine M4 receptors (M4Rs), VU0152100, attenuated the D1R agonist-stimulated ERK phosphorylation in the two regions, whereas the PAM itself did not alter basal ERK phosphorylation. All drug treatments had no effect on phosphorylation of c-Jun N-terminal kinases (JNKs), another MAPK subclass, in the striatum and mPFC. These results demonstrate that dopamine and acetylcholine are integrated to control synaptic ERK but not JNK activation in striatal and mPFC neurons in vivo. Activation of M4Rs exerts an inhibitory effect on the D1R-mediated upregulation of synaptic ERK phosphorylation. PMID- 26153450 TI - Time to endovascular reperfusion and degree of disability in acute stroke. AB - OBJECTIVE: Faster time from onset to recanalization (OTR) in acute ischemic stroke using endovascular therapy (ET) has been associated with better outcome. However, previous studies were based on less-effective first-generation devices, and analyzed only dichotomized disability outcomes, which may underestimate the full effect of treatment. METHODS: In the combined databases of the SWIFT and STAR trials, we identified patients treated with the Solitaire stent retriever with achievement of substantial reperfusion (Thrombolysis in Cerebral Infarction [TICI] 2b-3). Ordinal numbers needed to treat values were derived by populating joint outcome tables. RESULTS: Among 202 patients treated with ET with TICI 2b to 3 reperfusion, mean age was 68 (+/-13), 62% were female, and median National Institutes of Health Stroke Scale (NIHSS) score was 17 (interquartile range [IQR]: 14-20). Day 90 modified Rankin Scale (mRS) outcomes for OTR time intervals ranging from 180 to 480 minutes showed substantial time-related reductions in disability across the entire outcome range. Shorter OTR was associated with improved mean 90-day mRS (1.4 vs. 2.4 vs. 3.3, for OTR groups of 124-240 vs. 241 360 vs. 361-660 minutes; p < 0.001). The number of patients identified as benefitting from therapy with shorter OTR were 3-fold (range, 1.5-4.7) higher on ordinal, compared with dichotomized analysis. For every 15-minute acceleration of OTR, 34 per 1,000 treated patients had improved disability outcome. INTERPRETATION: Analysis of disability over the entire outcome range demonstrates a marked effect of shorter time to reperfusion upon improved clinical outcome, substantially higher than binary metrics. For every 5-minute delay in endovascular reperfusion, 1 of 100 patients has a worse disability outcome. PMID- 26153451 TI - Structural consequences of aglycosylated IgG Fc variants evolved for FcgammaRI binding. AB - In contrast to the glycosylated IgG antibodies secreted by human plasma cells, the aglycosylated IgG antibodies produced by bacteria are unable to bind FcgammaRs expressed on the surface of immune effector cells and cannot trigger immune effector functions. To avoid glycan heterogeneity problems, elicit novel effector functions, and produce therapeutic antibodies with effector function using a simple bacterial expression system, FcgammaRI-specific Fc-engineered aglycosylated antibodies, Fc11 (E382V) and Fc (E382V/M428I), containing mutations in the CH3 region, were isolated in a previous study. To elucidate the relationship between FcgammaRI binding affinity and the structural dynamics of the upper CH2 region of Fc induced by the CH3 mutations, the conformational variation of Fc variants was observed by single-molecule Forster resonance energy transfer (FRET) analysis using alternating-laser excitation (ALEX). In sharp contrast to wild-type Fc, which exhibits a highly dynamic upper CH2 region, the mutations in the CH3 region significantly stabilized the upper CH2 region. The results indicate that conformational plasticity, as well as the openness of the upper CH2 region, is critical for FcgammaR binding and therapeutic effector functions of IgG antibodies. PMID- 26153452 TI - Crustacean hemolymph microbiota: Endemic, tightly controlled, and utilization expectable. AB - Increasing number of evidence suggests that the hemolymph of numerous apparently healthy invertebrates is unsterile. Investigation of hemolymph microbiota properties and the homeostasis between host and bacteria is helpful to reveal bacteria pathogenesis, host immunity, and possible utilization in disease control. Crustaceans represent a large family of aquatic animals. Therefore, crustacean fishery is of important economic value worldwide. Research related to crustacean hemolymph microbiota has been performed over the years. In the present study, we conclude currently available information and present a comprehensive analysis regarding homeostasis between host and bacteria. In general, the presence of microbiota in crustacean hemolymph is an endemic event and can be influenced by internal and external factors. Opportunistic bacteria may have generated some changes or mutations under hemolymph stress. Meanwhile, hosts suppress hemolymph microbiota proliferation with the help of some critical antimicrobial peptides and lectins. The hemolymph microbiota may be beneficial for hosts as resistance against external damages. In addition, the hemolymph microbiota may be utilized in aquaculture. PMID- 26153455 TI - Obsessive-compulsive disorder concurrent with Melkersson-Rosenthal Syndrome: a case report. AB - OBJECTIVE: To describe a case of obsessive-compulsive disorder (OCD) comorbid with Melkersson-Rosenthal Syndrome (MRS). METHODS: We present a case study of comorbid OCD and MRS in a 13-year-old girl. RESULTS: She admitted to doubt obsessions and a control compulsion. The patient history included frequent facial palsy attacks, and she took prednisolone during each attack. She had her first such attack at 5 years of age, and she had suffered five attacks since then, the last one occurring 2 months before her presentation. Her obsessions began 1 week after the last attack. She was diagnosed MRS and concurrent OCD based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria. She was started on 20 mg/day fluoxetine. The control compulsion subsided during the second month of therapy, and the doubt obsessions improved significantly. CONCLUSION: Considering that the etiologies of MRS and childhood onset OCD have been attributed to infectious agents and autoimmune events, we conclude that both causes may play an important role in the etiology of these conditions. PMID- 26153454 TI - Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model. AB - BACKGROUND: Host-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity. An understanding of the host innate immune responses produced by different poxvirus vectors would aid in the assessment, selection and rational design of improved vaccines for human and veterinary applications. Novel avipoxviruses are being assessed to determine if they are different from other poxvirus vectors. Analysis of the transcriptome induced in a mouse model would aid in determining if there were significant differences between different poxvirus vectors which may reflect different adjuvant potential as well as establish if they should be further evaluated as vaccine vectors. RESULTS: We compared host transcript abundance in the spleens of BALB/c mice twenty four hours after intravenous infection (10(5) pfu/mouse) with six host-restricted poxvirus species from three genera, namely Lumpy Skin Disease virus (LSDV), Canarypox virus (CNPV), Fowlpox virus (FWPV), modified vaccinia Ankara (MVA) and two novel South African avipoxviruses, Feral Pigeonpox virus (FeP2) and Penguinpox virus (PEPV). These six viruses produced qualitatively and quantitatively distinct host responses with LSDV, followed by MVA, inducing the greatest interferon (IFN) response. FeP2 and PEPV caused very little change to host transcript abundance compared to the other 4 viruses tested. CNPV and FWPV induced the up regulation of two immunoglobulin genes (Ighg and Ighg3 (IgG3)) with CNPV inducing a third, Ighm (IgM). HIV-1-specific IgG3 antibodies have been correlated with decreased risk of HIV-1 infection in the RV144 trial, which included a CNPV-based vector (Yates et al. (Sci Transl Med, 6(228) p228, 2014). Up regulation of IgG3 by CNPV and FWPV but not the other poxviruses tested in vivo, implies that these two avipoxvirus-vector backbones may be involved in stimulation of the clinically important IgG3 antibody subclass. Differential transcript abundance associated with the different poxviruses is further discussed with particular emphasis on responses related to immune responses. CONCLUSION: Six, genetically diverse host-restricted poxviruses produce different responses in a mouse model early after infection. These differences may affect the immune response induced to vaccine antigen in vectors based on these viruses. The two novel avipoxviruses were clearly distinguishable from the other viruses. PMID- 26153456 TI - Depression--a common disorder across a broad spectrum of neurological conditions: a cross-sectional nationally representative survey. AB - OBJECTIVE: To estimate the prevalence of depression across a range of neurological conditions in a nationally representative sample. METHODS: The data source was the Survey of Living with Neurological Conditions in Canada (SLNCC), which accrued its sample by selecting participants from the Canadian Community Health Survey. The point prevalence of depression was estimated by assessment of depressive symptoms with the Patient Health Questionnaire, Brief (Patient Health Questionnaire, 9-item). RESULTS: A total of n=4408 participated in the SLNCC. The highest point prevalence of depression (>30%) was seen in those with traumatic brain injury and brain/spinal cord tumors. Depression was also highly prevalent (18-28%) in those with (listed from highest to lowest) Alzheimer's disease/dementia, dystonia, multiple sclerosis, Parkinson's disease, stroke, migraine, epilepsy and spina bifida. The odds ratios for depression, with the referent group being the general population, were significant (from highest to lowest) for migraine, traumatic brain injury, stroke, dystonia and epilepsy. CONCLUSIONS: All neurological conditions included in this study are associated with an elevated prevalence of depression in community populations. The conditions with the highest prevalence are traumatic brain injury and brain/spinal cord tumors. PMID- 26153457 TI - Pyrimidinone: versatile Trojan horse in DNA photodamage? AB - (6-4) Photolesions between adjacent pyrimidine DNA bases are prone to secondary photochemistry. It has been shown that singlet excited (6-4) moieties form Dewar valence isomers as well as triplet excitations. We here report on the triplet state of a minimal model for the (6-4) photolesion, 1-methyl-2(1H)-pyrimidinone. Emphasis is laid on its ability to abstract hydrogen atoms from alcohols and carbohydrates. Steady-state and time-resolved experiments consistently yield bimolecular rate constants of ~10(4) M(-1) s(-1) for the hydrogen abstraction. The process also occurs intramolecularly as experiments on zebularine (1-(beta-d ribofuranosyl)-2(1H)-pyrimidinone) show. PMID- 26153458 TI - Editorial Comment from Dr Nakamura to Identification of a subgroup with worse prognosis among patients with poor-risk testicular germ cell tumor. PMID- 26153460 TI - Nanostructured anatase TiO2 densified at high pressure as advanced visible light photocatalysts. AB - This study reports on characterization and photoactivity of nanostructured TiO2 samples, which have been permanently densified under high pressures, up to 2.1 GPa. Commercial Mirkat 211 anatase has been used as a benchmark sample, in order to investigate the effect of unidirectional high pressure on structural, optical and photocatalytic properties of TiO2. Vibrational Raman spectroscopy shows that the treatment does not cause transitions among the different crystalline phases of titanium dioxide. UV-vis diffuse reflectance spectra reveal that increasing pressure gives rise to a shift of the absorption onset towards higher wavelength enhancing the photoactivity under visible radiation. Samples are also photo electrochemically characterized and tested in the gas phase with partial oxidation of ethanol to acetaldehyde under visible irradiation. Compaction up to 0.8 GPa depresses both the alcohol conversion and the aldehyde yield, while samples treated under higher pressures show enhanced characteristics of conversion compared to the pristine material. Moreover, promising results in the reduction of CO2 are also obtained under UV-visible radiation. PMID- 26153459 TI - Read count-based method for high-throughput allelic genotyping of transposable elements and structural variants. AB - BACKGROUND: Like other structural variants, transposable element insertions can be highly polymorphic across individuals. Their functional impact, however, remains poorly understood. Current genome-wide approaches for genotyping insertion-site polymorphisms based on targeted or whole-genome sequencing remain very expensive and can lack accuracy, hence new large-scale genotyping methods are needed. RESULTS: We describe a high-throughput method for genotyping transposable element insertions and other types of structural variants that can be assayed by breakpoint PCR. The method relies on next-generation sequencing of multiplex, site-specific PCR amplification products and read count-based genotype calls. We show that this method is flexible, efficient (it does not require rounds of optimization), cost-effective and highly accurate. CONCLUSIONS: This method can benefit a wide range of applications from the routine genotyping of animal and plant populations to the functional study of structural variants in humans. PMID- 26153461 TI - FRET evidence for untwisting of amyloid fibrils on the surface of model membranes. AB - Apolipoprotein A-I (apoA-I) is an amyloid-forming protein whose amyloidogenic properties are attributed mainly to its N-terminal fragment. Cell membranes are thought to be the primary target for the toxic amyloid aggregates. In the present study Forster resonance energy transfer (FRET) between the membrane fluorescent probe Laurdan as a donor and amyloid-specific dye Thioflavin T (ThT) as an acceptor was employed to explore the interactions of amyloid fibrils from apoA-I variants 1-83/G26R and 1-83/G26R/W@8 with the model membranes composed of phosphatidylcholine and its mixture with cholesterol. The changes in FRET efficiency upon fibril-lipid binding were found to correlate with the extent of protein fibrillization. AFM imaging revealed the presence of two polymorphic states of fibrillar 1-83/G26R/W@8 with the helical and twisted ribbon morphologies. The simulation-based analysis of the experimental FRET profiles provided the arguments in favor of untwisting of fibrillar assemblies upon their interaction with the model membranes. Evidence for the face-on orientation and superficial bilayer location of the membrane-bound fragments of 1-83/G26R/W@8 fibrils was obtained. PMID- 26153462 TI - A novel family of katanin-like 2 protein isoforms (KATNAL2), interacting with nucleotide-binding proteins Nubp1 and Nubp2, are key regulators of different MT based processes in mammalian cells. AB - Katanins are microtubule (MT)-severing AAA proteins with high phylogenetic conservation throughout the eukaryotes. They have been functionally implicated in processes requiring MT remodeling, such as spindle assembly in mitosis and meiosis, assembly/disassembly of flagella and cilia and neuronal morphogenesis. Here, we uncover a novel family of katanin-like 2 proteins (KATNAL2) in mouse, consisting of five alternatively spliced isoforms encoded by the Katnal2 genomic locus. We further demonstrate that in vivo these isoforms are able to interact with themselves, with each other and moreover directly and independently with MRP/MinD-type P-loop NTPases Nubp1 and Nubp2, which are integral components of centrioles, negative regulators of ciliogenesis and implicated in centriole duplication in mammalian cells. We find KATNAL2 localized on interphase MTs, centrioles, mitotic spindle, midbody and the axoneme and basal body of sensory cilia in cultured murine cells. shRNAi of Katnal2 results in inefficient cytokinesis and severe phenotypes of enlarged cells and nuclei, increased numbers of centrioles and the manifestation of aberrant multipolar mitotic spindles, mitotic defects, chromosome bridges, multinuclearity, increased MT acetylation and an altered cell cycle pattern. Silencing or stable overexpression of KATNAL2 isoforms drastically reduces ciliogenesis. In conclusion, KATNAL2s are multitasking enzymes involved in the same cell type in critically important processes affecting cytokinesis, MT dynamics, and ciliogenesis and are also implicated in cell cycle progression. PMID- 26153464 TI - Some Remarks on Imaging of the Inner Ear: Options and Limitations. AB - The temporal bone has a highly complex anatomical structure, in which the sensory organs of the cochlea and the vestibular system are contained within a small space together with the sound-conducting system of the middle ear. Detailed imaging is thus required in this anatomical area. There are a great many clinical aims for which the highest-possible spatial resolution is required. These include the localization of cerebrospinal fluid fistulas, the detection of malformations of the middle and inner ear and the vestibulocochlear nerve, an aberrant course of the facial nerve and anomalies of the arterial and venous structures, the confirmation of dehiscence of the semicircular canals and finally, the verification of endolymphatic hydrops in cases of Meniere's disease. However, the term 'high resolution' is very time dependent. Two milestones in this respect have been (in 1991) the 3D visualization of the inner ear by means of maximum intensity projection (MIP) of a T2-weighted constructive interference in steady state (CISS) sequence of a 1.5-tesla magnetic resonance imaging (MRI) scanner (Tanioka et al., Radiology 178:141-144, 1991) and (in 1997) imaging of the vestibulocochlear nerve for the diagnosis of hypoplasia inside the internal auditory canal using the same sequence (Casselman et al., Radiology 202:773-781, 1997).The objective of this article is to highlight the options for, and the challenges of, contemporary imaging with regard to some clinical issues relating to the inner ear. PMID- 26153465 TI - A breeding experiment confirms the dominant mode of inheritance of the brown coat colour associated with the (496) Asp TYRP1 allele in goats. PMID- 26153466 TI - [Extended coronary dissection caused by severe polytrauma with contusio cordis : Venoarterial ECMO-assisted percutaneous coronary intervention]. AB - Treatment of a patient with acute cardiac failure due to a contusio cordis after polytrauma by an interdisciplinary team is reported. Shortly after admission to our shock room, the patient developed cardiogenic shock caused by an extended coronary dissection. After interim cardiopulmonary resuscitation, the patient was stabilized by venoarterial extracorporeal membrane oxygenation (ECMO) and subsequent complex coronary artery intervention in the heart catheter laboratory. Despite the increased left ventricular function which enabled partial weaning from the ECMO, the patient died of multiple organ failure 10 days after admission. PMID- 26153463 TI - DAG tales: the multiple faces of diacylglycerol--stereochemistry, metabolism, and signaling. AB - The neutral lipids diacylglycerols (DAGs) are involved in a plethora of metabolic pathways. They function as components of cellular membranes, as building blocks for glycero(phospho)lipids, and as lipid second messengers. Considering their central role in multiple metabolic processes and signaling pathways, cellular DAG levels require a tight regulation to ensure a constant and controlled availability. Interestingly, DAG species are versatile in their chemical structure. Besides the different fatty acid species esterified to the glycerol backbone, DAGs can occur in three different stereo/regioisoforms, each with unique biological properties. Recent scientific advances have revealed that DAG metabolizing enzymes generate and distinguish different DAG isoforms, and that only one DAG isoform holds signaling properties. Herein, we review the current knowledge of DAG stereochemistry and their impact on cellular metabolism and signaling. Further, we describe intracellular DAG turnover and its stereochemistry in a 3-pool model to illustrate the spatial and stereochemical separation and hereby the diversity of cellular DAG metabolism. PMID- 26153467 TI - Prospective assessment of white matter integrity in adult stem cell transplant recipients. AB - Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected <0.05) in the patient group compared to healthy controls. At baseline, patients treated with allogeneic HSCT had higher MD and AD in the left hemisphere WM than autologous HSCT patients (p-corrected <0.05). One year post-transplant, patients treated with allogeneic HSCT had lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the right hemisphere and left frontal WM compared to patients treated with autologous HSCT (p-corrected <0.05).There were modest but significant correlations between MD values and cognitive test scores, and these were greatest for timed tests and in projection tracts. Patients showed a trend toward a decline in working memory, and had lower cognitive test scores than healthy controls at the one-year assessment. The findings suggest a relatively diffuse pattern of alterations in WM integrity in adult survivors of HSCT. PMID- 26153468 TI - Hyper-connectivity of the thalamus during early stages following mild traumatic brain injury. AB - The thalamo-cortical resting state functional connectivity of seven sub-thalamic regions were examined in a prospectively recruited population of 77 acute mild TBI (mTBI) patients within the first 10 days (mean 6 +/- 3 days) of injury and 35 neurologically intact control subjects using the Oxford thalamic connectivity atlas. Neuropsychological assessments were conducted using the Automated Neuropsychological Assessment Metrics (ANAM). A subset of participants received a magentic resonance spectroscopy (MRS) exam to determine metabolite concentrations in the thalamus and the posterior cingulate cortex. Results show that patients performed worse than the control group on various subtests of ANAM and the weighted throughput score, suggesting reduced cognitive performance at this early stage of injury. Both voxel and region of interest based analysis of the resting state fMRI data demonstrated that acute mTBI patients have increased functional connectivity between the various sub-thalamic regions and cortical regions associated with sensory processing and the default mode network (DMN). In addition, a significant reduction in NAA/Cr was observed in the thalamus in the mTBI patients. Furthermore, an increase in Cho/Cr ratio specific to mTBI patients with self-reported sensory symptoms was observed compared to those without self reported sensory symptoms. These results provide novel insights into the neural mechanisms of the brain state related to internal rumination and arousal, which have implications for new interventions for mTBI patients with persistent symptoms. Furthermore, an understanding of heightened sensitivity to sensory related inputs during early stages of injury may facilitate enhanced prediction of safe return to work. PMID- 26153469 TI - Long-term Weight and Metabolic Effects of Laparoscopic Sleeve Gastrectomy Calibrated with a 50-Fr Bougie. AB - BACKGROUND: Most surgeons calibrate the sleeve with 32-French (Fr) to 40-Fr bougies hypothesizing that smaller bougies are associated with greater weight loss and long-term lower weight regain. The purpose of this study was to assess the weight loss results and resolution of comorbidities 5 years after laparoscopic sleeve gastrectomy (LSG). METHODS: A prospective study of all the morbidly obese patients undergoing laparoscopic sleeve gastrectomy calibrated with a 50-Fr bougie between October 2007 and February 2010 was performed. Excess weight loss (EWL) and remission of comorbidities were investigated at 1, 2, and 5 years after surgery. RESULTS: Fifty patients were included for the analysis. One year after surgery, mean excess weight loss (EWL) of 81.8 % was achieved, type 2 diabetes mellitus (T2DM) resolution rate was 76.9 %, hypertension resolution was observed in 73.3 %, sleep apnea hypopnea syndrome (SAHS) resolution in 100 % hypertriglyceridemia was normalized in all the cases, and hypercholesterolemia in 21.4 %. Two years after surgery, mean EWL was 84.4 % and comorbidity resolution rate similar to that obtained after the first postoperative year. Five years after surgery, mean EWL was 78.7 %, T2DM resolution 69.2 %, hypertension 66.7 %, SAHS 100 %, hypertriglyceridemia 100 %, and hypercholesterolemia 14.3 %. CONCLUSIONS: LSG calibrated with a 50-Fr bougie obtained excellent results in weight loss and resolution comorbidities and their maintenance in the long-term follow-up in our series. In our opinion, the results depend more on a preoperative correct selection of candidates and a close postoperative follow-up, rather than using a narrow calibration bougie. PMID- 26153472 TI - [Not Available]. PMID- 26153470 TI - Direct oral anticoagulants in atrial fibrillation: can data from randomized clinical trials be safely transferred to the general population? Yes. AB - Atrial fibrillation is the most common arrhythmia and is associated with significant morbidity and mortality. The current therapeutic options for patients at high thromboembolic risk include the vitamin K antagonists and the direct oral anticoagulants. These novel agents have been evaluated in more than 40,000 patients enrolled in four large randomized controlled trials for stroke prevention in non-valvular atrial fibrillation. When these results were pooled together, a greater efficacy profile, as well as a consistent reduction in life threatening bleeding was shown in comparison to vitamin K antagonists. Randomized controlled trials offer the highest level of evidence on the efficacy and safety of an intervention; however, their results may not be directly applicable to the general population. The results of a number of post-marketing observational studies from the United States and Europe have been published. The results of these studies substantially confirm the findings of the randomized trials and show a favorable safety profile with the use of the direct oral anticoagulants even in unselected populations. PMID- 26153473 TI - [Health Literacy and patient education in medical rehabilitation]. AB - Medical rehabilitation in Germany has a long tradition. It is covered by the statutory sickness funds and pension schemes, and is aimed at the prevention of work disability and need for nursing care due to chronic conditions. Chronically ill but health-literate patients - patients capable of making good health-related decisions, or of participating strongly in this decision making - have better health outcomes. To enhance health literacy and participation, medical rehabilitation relies heavily on patient education. This article describes health literacy from the perspective of educational research, outlines the basics of learning principles, and draws conclusions for developing patient education programmes in medical rehabilitation. Implementing a constructivist learning paradigm promotes changes within the trainer team and within the rehabilitation institution - turning it into a health-literate health care organisation. Health literacy in medical rehabilitation is aimed at neither turning the patient into a physician nor replacing evidence-based recommendations through subjective preferences. Medical rehabilitation reaches patients best by using modern health education programmes based on findings from education research, theoretically founded and directed towards building competencies. Furthermore, an educationally qualified training team and a rehabilitation institution are essential in enabling formal and informal learning processes. PMID- 26153475 TI - The Current Knowledge and Confidence of Rheumatology Nurses in Providing Advice on Pain Management. PMID- 26153476 TI - Cardiorespiratory Capacity and Leukocyte Telomere Length Among Adults in the United States. AB - Short leukocyte telomere length (LTL) has become a hallmark characteristic of aging and is associated with higher morbidity and mortality. Physical activity (PA) has been implicated in attenuating age-induced diseases by, for example, preserving LTL. Results from studies of the relationship between PA and LTL have been mixed, which might be because PA was assessed over a short period of time. There have been few studies in which investigators have examined the association between LTL and cardiorespiratory fitness (CRF), an enduring trait influenced by chronic habituation of PA that takes place over months or years. The purpose of the present study was to examine the association between CRF and LTL in a national sample of US adults who were 20-49 years of age from the 1999-2002 National Health and Nutrition Examination Survey (n = 1,764). LTL was assessed using quantitative polymerase chain reaction, and CRF assessed using a treadmill based exercise test. After adjustments, compared with subjects in the lowest CRF tertile, those in the middle tertile (beta = 0.03, 95% confidence interval: 0.005, 0.06; P = 0.02) and upper tertile (beta = 0.05, 95% confidence interval: 0.004, 0.09; P = 0.04) had longer LTL. These findings suggest that higher CRF is associated with longer LTL. PMID- 26153474 TI - Stroke associated with coronary artery bypass grafting. AB - While coronary artery bypass grafting (CABG) has been playing a significant role in the revascularization for ischemic heart disease, neurological complications associated with CABG have been a primary concern. Stroke, although the incidence is low, is one of the most devastating complication of CABG. Many studies have identified the risk factors for stroke with CABG, such as prior stroke, carotid artery stenosis, aortic atherosclerosis, atrial fibrillation and cardiopulmonary bypass. Various rational approaches focusing on individual risk factor have been proposed for the stroke. Prophylactic carotid revascularization is an important strategy, and the diagnosis of carotid stenosis has to be established correctly. Prevention of emboli from aortic plaque is also an essential issue. Intraoperative monitoring with transesophageal or epiaortic ultrasound is useful to identify mobile atheromatous plaques and to select appropriate aortic manipulations. Maintenance of cerebral blood flow and blood pressure during cardiopulmonary bypass might be critical issues. Besides, there are conflicting two opinions regarding off-pump CABG; one supports an efficiency for the prevention of stroke while the other advocates no effect. This discrepancy might be explained by the difference of the risk of stroke in the population of the individual study and by the variation of the percentage of aortic clamping or aortic anastomosis in each study. Pharmaceutical therapies such as statin, preventive medication for atrial fibrillation, or antiplatelet are promising methods. Although it is hard to decrease the incidence of the stroke with any single countermeasure, sustained effort should be continued to overcome the stroke associated with CABG. PMID- 26153477 TI - Three Authors Reply. PMID- 26153478 TI - Re: "A Prospective Study of Fitness, Fatness, and Depressive Symptoms". PMID- 26153479 TI - Evaluation of Moderate Alcohol Use With QT Interval and Heart Rate Using Mendelian Randomization Analysis Among Older Southern Chinese Men in the Guangzhou Biobank Cohort Study. AB - Western observational studies show that moderate alcohol use is associated with lower cardiovascular disease (CVD) risk, but these associations may be confounded by the healthier attributes of moderate users in these settings. Mendelian randomization analysis may help to ascertain the causal effect of moderate alcohol use on specific factors related to CVD and thereby clarify the role of alcohol. We used Mendelian randomization analysis with the aldehyde dehydrogenase 2 gene (ALDH2) as an instrumental variable to examine the association of alcohol units (10 g of ethanol) per day with heart rate-corrected QT interval and heart rate assessed from electrocardiogram among 4,588 older southern Chinese men in the Guangzhou Biobank Cohort Study (2003-2008). The F statistic was 77 for ALDH2 on alcohol use, suggesting little weak-instrument bias. Instrumental variable analysis showed that alcohol units were not associated with the corrected QT interval, with beta = 1.04 (95% confidence interval: -0.61, 2.70) milliseconds, but they were associated with increased heart rate, with beta = 0.98 (95% confidence interval: 0.04, 1.92) beat per minute. This study suggests that moderate alcohol use in men is not beneficial for heart function via QT interval or heart rate but could be detrimental. Future studies using specific cardiovascular outcomes may elucidate how alcohol affects different aspects of the cardiovascular system and, hence, the overall effects of alcohol on CVD can be estimated. PMID- 26153480 TI - Safety and clinical effectiveness of drug-eluting stents for saphenous vein graft intervention in older individuals: Results from the medicare-linked National Cardiovascular Data Registry((r)) CathPCI Registry((r)) (2005-2009). AB - OBJECTIVES: To evaluate the safety of drug-eluting stents (DES) when treating patients with failing saphenous vein grafts (SVG). BACKGROUND: DES reduce target vessel revascularization in patients with failing SVGs; however, compared with bare metal stents (BMS), DES have been variably associated with increased mortality. METHODS: Clinical records from National Cardiovascular Data Registry((r)) CathPCI Registry((r)) (49,325 older individuals [>=65 years] who underwent SVG stenting 2005-2009) were linked to Medicare claims to create a longitudinal record. Death, myocardial infarction (MI), and urgent revascularization with DES versus BMS were evaluated to 3 years using propensity matching (PM). Results were stratified by clinical presentation (acute coronary syndrome [ACS], non-ACS), previous lesion treatment (in-stent, de novo), and graft segment (aortic, body, distal anastomosis). RESULTS: In this older cohort (median age, 75 years), acute presentations were prevalent (ACS, 69%; TIMI flow <3, 45%), and adverse clinical outcomes were common by 3 years (death, 24.5%; MI, 14.6%; urgent revascularization, 29.5%). Among DES patients (n = 31,403), 3-year mortality was lower (vs. BMS) (22.7% vs. 28.0%, P < 0.001; PM hazard ratio [HR] 0.87, 95% confidence interval 0.83-0.91), and no difference was observed in the adjusted risk for MI (PM HR 0.97, 0.91 to 1.03) or urgent revascularization (PM HR 1.04, 0.99-1.08). These findings were independent of clinical presentation, previous lesion treatment, and graft segment (P interaction, ns). CONCLUSIONS: In this large SVG PCI cohort, all-cause mortality was lower among those receiving DES, and no difference in MI or urgent revascularization was observed to 3 years. (c) 2015 Wiley Periodicals, Inc. PMID- 26153481 TI - Influence of weaning age on the villous height and disaccharidase activities in the porcine small intestine. AB - Body weight gain after weaning is correlated with villous height and disaccharidase activity. This evidence suggests that the maintenance of the small intestinal structure and function after weaning is important for the growth of piglets. We demonstrated that the influence of weaning age was obtained by disaccharidase activities and villous height in eight sections of the porcine small intestine. Therefore, we designed three weaning ages (weaned at the ages of 14, 21 or 28 days) and the piglets were slaughtered after 7 or 14 days post weaning. The remaining suckling piglets were slaughtered at the age of 1, 7, 14, 21 and 28 days. Four piglets were slaughtered at each event; therefore, 44 piglets were used in this study. Villous height and disaccharidase activities were measured in each section of the small intestine. Early weaning such as that at 14 days had severe influence on villous and disaccharidase activities. In particular, weaning of 14-day-olds did not result in maltase activity at least 2 weeks post-weaning. Accordingly, the weaning age of crossbred piglets is recommended to be at least 21 days or more on the basis of villous height and disaccharidase activity analyses. PMID- 26153482 TI - A semi-quantitative and thematic analysis of medical student attitudes towards M Learning. AB - RATIONALE, AIMS AND OBJECTIVES: Smartphone and mobile application technology have in recent years furthered the development of novel learning and assessment resources. 'MBChB Mobile' is a pioneering mobile learning (M-Learning) programme at University of Leeds, United Kingdom and provides all senior medical students with iPhone handsets complete with academic applications, assessment software and a virtual reflective environment. This study aimed to evaluate the impact of MBChB Mobile on student learning. METHODS: Ethical approval was granted to invite fourth and fifth year medical students to participate in a semi-quantitative questionnaire: data were collected anonymously with informed consent and analysed where appropriate using chi-squared test of association. Qualitative data generated through focus group participation were subjected to both content and thematic analysis. RESULTS: A total of 278 of 519 (53.6%) invited participants responded. Overall, 72.6% of students agreed that MBChB Mobile enhanced their learning experience; however, this was significantly related to overall usage (P < 0.001) and self-reported mobile technology proficiency (P < 0.001). Qualitative data revealed barriers to efficacy including technical software issues, non transferability to different mobile devices, and perceived patient acceptability. CONCLUSIONS: As one of the largest evaluative and only quantitative study of smartphone-assisted M-Learning in undergraduate medical education, MBChB Mobile suggests that smartphone and application technology enhances students' learning experience. Barriers to implementation may be addressed through the provision of tailored learning resources, along with user-defined support systems, and appropriate means of ensuring acceptability to patients. PMID- 26153483 TI - Influence of Tricuspid Bioprosthetic Mitral Valve Orientation Regarding the Flow Field Inside the Left Ventricle: In Vitro Hydrodynamic Characterization Based on 2D PIV Measurements. AB - The flow patterns of a prosthetic heart valve in the aortic or mitral position can change according to its type and orientation. This work describes the use of 2D particle image velocimetry (PIV) applied to the in vitro flow fields characterization inside the upper part of a left ventricular model at various heart rates and as a function of two orientations of stented tricuspid mitral bioprostheses. In the ventricular model, each mitral bioprosthesis (27 and 31 mm diameter) was installed in two orientations, rotated by 180 degrees , while the aortic bileaflet mechanical valve (27 mm diameter) remained in a fixed orientation. The results (N = 50) showed changes in the intraventricular flow fields according to the mitral bioprostheses positioning. Also, changes in the aortic upstream velocity profiles were noticed as a function of mitral orientations. PMID- 26153484 TI - A J-Shaped Association Between Serum Uric Acid Level and Allograft Outcomes After Living Donor Kidney Transplantation. AB - Hyperuricemia following kidney transplantation (KT) may contribute to a decline in allograft renal function, but be affected by KT-related confounding factors. Some studies have even suggested that a reduction in serum uric acid (UA) is associated with poor patient outcomes. Thus, we retrospectively analyzed the impact of serum UA on allograft outcomes in 281 KT recipients. KT recipients were divided into five groups according to serum UA level (mg/dL): Group I (n = 46), <= 5; Group II (n = 62), > 5 and <= 6; Group III (n = 70), > 6 and <= 7; Group IV (n = 53), > 7 and <= 8; Group V (n = 50), > 8. Regression analysis showed that serum UA level was significantly associated with future allograft function. In a Kaplan-Meier analysis, the dialysis-free survival of Group II recipients was better than that of the other groups (Group I, 140 +/- 5 months; Group II, 208 +/ 7 months; Group III, 148 +/- 4 months; Group IV, 185 +/- 12 months; Group V, 164 +/- 11 months; P = 0.0164). In Cox proportional hazard models adjusting for estimated glomerular filtration rate, the relative risk of allograft loss still tended to be elevated in Group I (HR=3.417, 95% CI 1.138-10.258) and Group V (HR=2.793, 95% CI 1.108-7.041), using Group II as the reference. Our results suggest that there is a J-shaped association between serum UA levels and allograft outcomes in living donor KT recipients. PMID- 26153485 TI - Role of contextualizing a crisis scenario on the performance of a cricothyrotomy procedural task. AB - PURPOSE: Simulation is an important alternative to evaluate cricothyrotomy, a rare life-saving procedure. This crossover study aimed to determine whether contextualization of a crisis scenario would impact the performance of a cricothyrotomy procedural task. METHODS: Sixty-five anesthesia assistants and emergency medicine and anesthesia residents underwent a teaching session in surgical cricothyrotomy using one of two sets of cricothyrotomy kits: the Portex 6.0 and Melker 3.5 (n = 32) or the Portex 6.0 and Melker 5.0 (n = 33). Within six weeks following the session, the participants performed cricothyrotomies on a full-body patient mannequin simulator coupled with a porcine larynx (tissue mannequin simulator) using the assigned two kits in a "cannot intubate, cannot ventilate" (CICV) contextualized scenario (CS) and in a CICV verbalized non contextualized scenario (NCS). Each participant performed a total of four cricothyrotomies using the two kits in the two scenarios. The primary outcome measure was insertion time, and secondary outcome measures were severity of injuries and failure rate. Outcome measures were compared between scenarios for each kit. RESULTS: Mean (SD) insertion time for a successful cricothyrotomy was not significantly different between NCS and CS for the Melker 3.5 [83.0 (45.0) sec vs 63.3 (36.1) sec, respectively; P = 0.96; mean difference (MD), 19.7 sec; 95% confidence interval (CI), -1.9 to 41.3], the Melker 5.0 [86.5 (36.8) sec vs 107.1 (55.6) sec, respectively; P = 0.11; MD, -20.6 sec; 95% CI, -44.9 to 3.7], and the Portex 6.0 [59.5 (35.5) sec vs 59.0 (35.0) sec, respectively; P = 0.95; MD, 0.5 sec; 95% CI, -13.2 to 14.2]. Failure rate and severity of injuries, measured as mean average injury score for each kit, were also similar between scenarios. CONCLUSIONS: Contextualization of a crisis scenario did not affect the performance of a cricothyrotomy procedural task on a tissue-mannequin simulator. These findings may have implications when considering the feasibility and cost effectiveness for assessing the performance of cricothyrotomy procedural tasks. PMID- 26153486 TI - Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alpha Synuclein Overexpressing Transgenic Mouse Model of Parkinson's Disease: A Pilot Study. AB - Evidence suggests that accumulation and aggregation of alpha-synuclein contribute to the pathogenesis of Parkinson's disease (PD). The aim of this study was to evaluate whether diffusion kurtosis imaging (DKI) will provide a sensitive tool for differentiating between alpha-synuclein-overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. This experiment was designed as a proof-of-concept study and forms a part of a complex protocol and ongoing translational research. Nine-month-old TNWT-61 mice and age-matched WT littermates underwent behavioral tests to monitor motor impairment and MRI scanning using 9.4 Tesla system in vivo. Tract-based spatial statistics (TBSS) and the DKI protocol were used to compare the whole brain white matter of TNWT-61 and WT mice. In addition, region of interest (ROI) analysis was performed in gray matter regions such as substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus known to show higher accumulation of alpha-synuclein. For the ROI analysis, both DKI (6 b-values) protocol and conventional (2 b-values) diffusion tensor imaging (cDTI) protocol were used. TNWT-61 mice showed significant impairment of motor coordination. With the DKI protocol, mean, axial, and radial kurtosis were found to be significantly elevated, whereas mean and radial diffusivity were decreased in the TNWT-61 group compared to that in the WT controls with both TBSS and ROI analysis. With the cDTI protocol, the ROI analysis showed decrease in all diffusivity parameters in TNWT-61 mice. The current study provides evidence that DKI by providing both kurtosis and diffusivity parameters gives unique information that is complementary to cDTI for in vivo detection of pathological changes that underlie PD-like symptomatology in TNWT-61 mouse model of PD. This result is a crucial step in search for a candidate diagnostic biomarker with translational potential and relevance for human studies. PMID- 26153487 TI - Cobalt-Induced Ototoxicity in Rat Postnatal Cochlear Organotypic Cultures. AB - Cobalt (Co) is a required divalent metal used in the production of metal alloys, batteries, and pigments and is a component of vitamin B12. Excessive uptake of Co is neurotoxic causing temporary or permanent hearing loss; however, its ototoxic effects on the sensory hair cells, neurons, and support cells in the cochlea are poorly understood. Accordingly, we treated postnatal day 3 rat cochlear organotypic cultures with various doses and durations of CoCl2 and quantified the damage to the hair cells, peripheral auditory nerve fibers, and spiral ganglion neurons (SGN). Five-day treatment with 250 MUM CoCl2 caused extensive damage to hair cells and neurons which increased with dose and treatment duration. CoCl2 caused greater damage to outer hair cells than inner hair cells; damage was greatest in the base of the cochlea and decreased towards the base. CoCl2 increased expression of superoxide radical in hair cells and SGNs and SGN loss was characterized by nuclear condensation and fragmentation, morphological features of apoptosis. CoCl2 treatment increased the expression of caspase-3 indicative of caspase-mediated programmed cell death. These results identify hair cells and spiral ganglion neurons as the main targets of Co ototoxicity in vitro and implicate the superoxide radical as a trigger of caspase-mediated ototoxicity. PMID- 26153489 TI - Let's Move for Pacific Islander Communities: an Evidence-Based Intervention to Increase Physical Activity. AB - Pacific Islander (PI) populations of Southern California experience high obesity and low physical activity levels. Given PI's rich cultural ties, efforts to increase physical activity using a community-tailored strategy may motivate members in a more sustainable manner. In this paper, we (1) detail the program adaptation methodology that was utilized to develop the Weaving an Islander Network for Cancer Awareness, Research and Training (WINCART) Center's PI Let's Move Program, a culturally tailored program aimed to increase physical activity levels among members of PI organizations in Southern California, and (2) share the program's pilot evaluation results on individual and organizational changes. The WINCART Center applied the National Cancer Institute's program adaptation guidelines to tailor the evidence-based Instant Recess program to fit the needs of PIs. The end product, the PI Let's Move Program, was piloted in 2012 with eight PI organizations, reaching 106 PI adults. At baseline, 52 % of participants reported that they were not physically active, with the average number of days engaged in medium-intensity physical activity at 2.09 days/week. After the 2 month program, participants increased the number of days that they engaged in medium-intensity physical activity from 2.09 to 2.90 days/week. Post-pilot results found that 82 % of participants reported intentions to engage in physical activity for at least the next 6 months. At baseline, only one organization was currently implementing a physical activity program, and none had implemented an evidence-based physical activity program tailored for PIs. After the 2-month timeframe, despite varying levels of capacity, all eight organizations were able to successfully implement the program. In conclusion, results from our program provide evidence that disparity populations, such as PIs, can be successfully reached through programs that are culturally tailored to both individuals and their community organizations. PMID- 26153488 TI - Case Files from the University of California San Diego Health System Fellowship Coma and Severe Acidosis: Remember to Consider Acetaminophen. PMID- 26153490 TI - Medical Student Knowledge of Oncology and Related Disciplines: a Targeted Needs Assessment. AB - Despite increasing numbers of cancer survivors, non-oncology physicians report discomfort and little training regarding oncologic and survivorship care. This pilot study assesses medical student comfort with medical oncology, surgical oncology, radiation oncology, hospice/palliative medicine, and survivorship care. A survey was developed with input from specialists in various fields of oncologic care at a National Cancer Institute-designated comprehensive cancer center. The survey included respondent demographics, reports of experience with oncology, comfort ratings with oncologic care, and five clinical vignettes. Responses were yes/no, multiple choice, Likert scale, or free response. The survey was distributed via email to medical students (MS1-4) at two US medical schools. The 105 respondents were 34 MS1s (32 %), 15 MS2s and MD/PhDs (14 %), 26 MS3s (25 %), and 30 MS4s (29 %). Medical oncology, surgical oncology, and hospice/palliative medicine demonstrated a significant trend for increased comfort from MS1 to MS4, but radiation oncology and survivorship care did not. MS3s and MS4s reported the least experience with survivorship care and radiation oncology. In the clinical vignettes, students performed the worst on the long-term chemotherapy toxicity and hospice/palliative medicine questions. Medical students report learning about components of oncologic care, but lack overall comfort with oncologic care. Medical students also fail to develop an increased self-assessed level of comfort with radiation oncology and survivorship care. These pilot results support development of a formalized multidisciplinary medical school oncology curriculum at these two institutions. An expanded national survey is being developed to confirm these preliminary findings. PMID- 26153495 TI - BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. AB - BACKGROUND: While the negative prognostic role of BRAF V600E mutation in metastatic colorectal cancer (mCRC) is well established, the impact of BRAF codons 594 and 596 mutations, occurring in <1% of CRCs, is completely unknown. The present work aims to describe clinical, pathological and molecular features and prognosis of BRAF codons 594 and 596 mutant mCRCs, compared with BRAF V600E mutant and wild-type ones. PATIENTS AND METHODS: Patients treated for mCRC at three Italian Institutions between October 2006 and October 2014, with available KRAS and NRAS codon 12, 13, 59, 61, 117 and 146 and BRAF codon 594, 596 and 600 mutational status, as detected by means of direct sequencing or matrix assisted laser desorption ionization time-of-flight MassArray, were included. RESULTS: Ten patients bearing BRAF codons 594 or 596 mutated tumors were identified and compared with 77 and 542 patients bearing BRAF V600E mutated and BRAF wild-type tumors, respectively. While BRAF V600E mutated tumors were more frequently right sided, mucinous and with peritoneal spread, BRAF 594 or 596 mutated were more frequently rectal, nonmucinous and with no peritoneal spread. All BRAF 594 or 596 mutated tumors were microsatellite stable. Patients with BRAF codons 594 or 596 mutated tumors had markedly longer overall survival (OS) when compared with BRAF V600E mutated [median OS: 62.0 versus 12.6 months; hazard ratio: 0.36 (95% confidence interval 0.20-0.64), P = 0.002], both at univariate and multivariate analyses. CONCLUSIONS: BRAF codon 594 or 596 mutated mCRCs are different from BRAF V600E ones in terms of molecular features, pathological characteristics and clinical outcome. This is consistent with preclinical evidences of a kinase inactivating effect of these mutations. The role of CRAF in transducing the intracellular signal downstream BRAF 594 or 596 mutated proteins opens the way to further preclinical investigation. PMID- 26153496 TI - A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). AB - BACKGROUND: A previous randomized phase II study demonstrated that the addition of a c-Met inhibitor tivantinib to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib might prolong progression-free survival (PFS) in patients with previously treated, nonsquamous nonsmall-cell lung cancer (NSCLC). On a subset analysis, the survival benefit was greater in patients with wild-type EGFR (WT-EGFR) than in those with activating EGFR mutations. Herein, this phase III study compared overall survival (OS) between Asian nonsquamous NSCLC patients with WT-EGFR who received erlotinib plus tivantinib (tivantinib group) or erlotinib plus placebo (placebo group). METHODS: A total of 460 NSCLC patients were planned to be randomized to the tivantinib or placebo group. Primary end point was OS. Secondary end points were PFS, tumor response, and safety. Tissue was collected for biomarker analysis, including c-Met and HGF expression. RESULTS: Enrollment was stopped when 307 patients were randomized, following the Safety Review Committee's recommendation based on an imbalance in the interstitial lung disease (ILD) incidence between the groups. ILD developed in 14 patients (3 deaths) and 6 patients (0 deaths) in the tivantinib and the placebo groups, respectively. In the enrolled patients, median OS was 12.7 and 11.1 months in the tivantinib and the placebo groups, respectively [hazard ratio (HR) = 0.891, P = 0.427]. Median PFS was 2.9 and 2.0 months in the tivantinib and the placebo groups, respectively (HR = 0.719, P = 0.019). The commonly observed grade >= 3 adverse events in the tivantinib group were neutropenia (24.3%), leukopenia (18.4%), febrile neutropenia (13.8%), and anemia (13.2%). CONCLUSIONS: This study was prematurely terminated due to the increased ILD incidence in the tivantinib group. Although this study lacked statistical power because of the premature termination and did not demonstrate an improvement in OS, our results suggest that tivantinib plus erlotinib might improve PFS than erlotinib alone in nonsquamous NSCLC patients with WT-EGFR. TRIAL REGISTRATION NUMBER: NCT01377376. PMID- 26153497 TI - Reply to letter to the editor 'Primum non nocere' by Templeton and Seruga. PMID- 26153498 TI - Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple-negative breast cancer model. AB - BACKGROUND: Triple-negative breast cancers (TNBC) are considered the most aggressive type of breast cancer, for which no targeted therapy exists at the moment. These tumors are characterized by having a high degree of chromosome instability and often overexpress the spindle assembly checkpoint kinase TTK. To explore the potential of TTK inhibition as a targeted therapy in TNBC, we developed a highly potent and selective small molecule inhibitor of TTK, NTRC 0066-0. RESULTS AND CONCLUSIONS: The compound is characterized by long residence time on the target and inhibits the proliferation of a wide variety of human cancer cell lines with potency in the same range as marketed cytotoxic agents. In cell lines and in mice, NTRC 0066-0 inhibits the phosphorylation of a TTK substrate and induces chromosome missegregation. NTRC 0066-0 inhibits tumor growth in MDA-MB-231 xenografts as a single agent after oral application. To address the effect of the inhibitor in breast cancer, we used a well-defined mouse model that spontaneously develops breast tumors that share key morphologic and molecular features with human TNBC. Our studies show that combination of NTRC 0066-0 with a therapeutic dose of docetaxel resulted in doubling of mouse survival and extended tumor remission, without toxicity. Furthermore, we observed that treatment efficacy is only achieved upon co-administration of the two compounds, which suggests a synergistic in vivo effect. Therefore, we propose TTK inhibition as a novel therapeutic target for neoadjuvant therapy in TNBC. PMID- 26153499 TI - BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance. AB - BACKGROUND: Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. DESIGN: Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. RESULTS AND CONCLUSION: Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use. PMID- 26153501 TI - Influence of nitrogen source and pH value on undesired poly(gamma-glutamic acid) formation of a protease producing Bacillus licheniformis strain. AB - Bacillus spp. are used for the production of industrial enzymes but are also known to be capable of producing biopolymers such as poly(gamma-glutamic acid). Biopolymers increase the viscosity of the fermentation broth, thereby impairing mixing, gas/liquid mass and heat transfer in any bioreactor system. Undesired biopolymer formation has a significant impact on the fermentation and downstream processing performance. This study shows how undesirable poly(gamma-glutamic acid) formation of an industrial protease producing Bacillus licheniformis strain was prevented by switching the nitrogen source from ammonium to nitrate. The viscosity was reduced from 32 to 2.5 mPa s. A constant or changing pH value did not influence the poly(gamma-glutamic acid) production. Protease production was not affected: protease activities of 38 and 46 U mL(-1) were obtained for ammonium and nitrate, respectively. With the presented results, protease production with industrial Bacillus strains is now possible without the negative impact on fermentation and downstream processing by undesired poly(gamma-glutamic acid) formation. PMID- 26153500 TI - Natural and engineered biosynthesis of nucleoside antibiotics in Actinomycetes. AB - Nucleoside antibiotics constitute an important family of microbial natural products bearing diverse bioactivities and unusual structural features. Their biosynthetic logics are unique with involvement of complex multi-enzymatic reactions leading to the intricate molecules from simple building blocks. Understanding how nature builds this family of antibiotics in post-genomic era sets the stage for rational enhancement of their production, and also paves the way for targeted persuasion of the cell factories to make artificial designer nucleoside drugs and leads via synthetic biology approaches. In this review, we discuss the recent progress and perspectives on the natural and engineered biosynthesis of nucleoside antibiotics. PMID- 26153502 TI - Influence of glucose fermentation on CO2 assimilation to acetate in homoacetogen Blautia coccoides GA-1. AB - Fermentation of glucose influences CO2 assimilation to acetate in homoacetogens. Blautia coccoides was investigated for a better understanding of the metabolic characteristics of homoacetogens in mixotrophic cultures. Batch cultures of the strain with H2/CO2 as a sole carbon source reached an acetate yield of 5.32 g/g dry cell weight after 240 h of incubation. Autotrophic metabolism was inhibited as glucose was added into the culture: the higher the glucose concentration the lower the autotrophic ability of the bacterium. Autotrophy was inhibited by high glucose concentration, probably due to the competition for coenzyme A between the Embden-Meyerhof-Parnas pathway and the Wood-Ljungdahl carbon fixation pathway, the energy (adenosine triphosphate) allocation for synthesis of cell carbon and reduction of CO2, in combination with the low pH caused by the accumulation of acetate. PMID- 26153503 TI - Exploring medium-chain-length polyhydroxyalkanoates production in the engineered yeast Yarrowia lipolytica. AB - Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are a large class of biopolymers that have attracted extensive attention as renewable and biodegradable bio-plastics. They are naturally synthesized via fatty acid de novo biosynthesis pathway or beta-oxidation pathway from Pseudomonads. The unconventional yeast Yarrowia lipolytica has excellent lipid/fatty acid catabolism and anabolism capacity depending of the mode of culture. Nevertheless, it cannot naturally synthesize PHA, as it does not express an intrinsic PHA synthase. Here, we constructed a genetically modified strain of Y. lipolytica by heterologously expressing PhaC1 gene from P. aeruginosa PAO1 with a PTS1 peroxisomal signal. When in single copy, the codon optimized PhaC1 allowed the synthesis of 0.205 % DCW of PHA after 72 h cultivation in YNBD medium containing 0.1 % oleic acid. By using a multi-copy integration strategy, PHA content increased to 2.84 % DCW when the concentration of oleic acid in YNBD was 1.0 %. Furthermore, when the recombinant yeast was grown in the medium containing triolein, PHA accumulated up to 5.0 % DCW with as high as 21.9 g/L DCW, which represented 1.11 g/L in the culture. Our results demonstrated the potential use of Y. lipolytica as a promising microbial cell factory for PHA production using food waste, which contains lipids and other essential nutrients. PMID- 26153504 TI - Empowering clinical data collection at the point of care. PMID- 26153505 TI - Recent advances in the management of Duchenne muscular dystrophy. AB - Duchenne muscular dystrophy (DMD) is the commonest inherited neuromuscular disorder of childhood and mainly affects males. Over the course of the last century, the average life expectancy of these patients has doubled and now stands at ~25 years. This progress has been made possible through advances in the diagnosis, treatment and long-term care of patients with DMD. Basic and clinical research, national and international scientific networks, and parent and patient support groups have all contributed to achieving this goal. The advent of molecular genetic therapies and personalised medicine has opened up new avenues and raised hopes that one day a cure for this debilitating orphan disease will be found. The main purpose of this short review is to enable paediatricians to have informed discussions with parents of boys with DMD about recent scientific advances affecting their child's clinical care. PMID- 26153506 TI - Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence. AB - Growth hormone deficiency (GHD) is a rare but important cause of short stature in childhood with a prevalence of 1 in 4000. The diagnosis is currently based on an assessment of auxology along with supporting evidence from biochemical and neuroradiological studies. There are significant controversies in the diagnosis and management of GHD. Growth hormone (GH) stimulation tests continue to play a key role in GHD diagnosis but the measured GH concentration can vary significantly with stimulation test and GH assay used, creating difficulties for diagnostic accuracy. Such issues along with the use of adjunct biochemical markers such as IGF-I and IGFBP-3 for the diagnosis of GHD, will be discussed in this review. Additionally, the treatment of GHD remains a source of much debate; there is no consensus on the best mechanism for determining the starting dose of GH in patients with GHD. Weight and prediction based models will be discussed along with different mechanisms for dose adjustment during treatment (auxology or IGF-I targeting approaches). At the end of growth and childhood treatment, many subjects diagnosed with isolated GHD re-test normal. It is not clear if this represents a form of transient GHD or a false positive diagnosis during childhood. Given the difficulties inherent in the diagnosis of GHD, an early reassessment of the diagnosis in those who respond poorly to GH is to be recommended. PMID- 26153507 TI - Newborn manikin study shows that physicians often fail to detect correct lung compliance when using a self-inflating bag. AB - AIM: Recognising changes in lung compliance can help clinicians to adjust initial inflations during resuscitation at birth. We examined whether physicians sensed low and normal compliance with a self-inflating bag before and after an educational intervention that used a manikin connected to a newborn lung simulator. METHODS: We asked 43 physicians with neonatal duties to perform two low compliance ventilation attempts and two normal-compliance ventilation attempts in a randomised order at baseline and after the educational intervention, with 34 taking part in a retest three months later. RESULTS: The physicians correctly recognised low and normal compliance in 71% and 66% of the ventilations at baseline, 80% and 66% of the ventilations after the intervention and 74% and 81% at retest. Correct recognition of normal compliance improved from baseline to retest (p = 0.04). Ventilations in low- vs normal-compliance settings resulted in lower tidal volumes (4.4 vs 23.0 mL, p < 0.001), lower ventilation rates (42 vs 51, p < 0.001) and higher peak inflating pressure (35.2 vs 31.4 cmH2 O, p < 0.001). CONCLUSION: Around one in four physicians failed to recognise correct compliance levels when using a self-inflating bag and showed limited improvement after an educational intervention. Ventilations in a low-compliance setting resulted in suboptimal ventilation. PMID- 26153508 TI - Prodromal Transient Ischemic Attack or Minor Stroke and Outcome in Basilar Artery Occlusion. AB - BACKGROUND: The presence of prodromal transient ischemic attacks (TIAs) has been associated with a favorable outcome in anterior circulation stroke. We aimed to determine the association between prodromal TIAs or minor stroke and outcomes at 1 month, in the Basilar Artery International Cooperation Study, a registry of patients presenting with an acute symptomatic and radiologically confirmed basilar artery occlusion. METHODS: A total of 619 patients were enrolled in the registry. Information on prodromal TIAs was available for 517 patients and on prodromal stroke for 487 patients. We calculated risk ratios and corresponding 95% confidence intervals (CIs) for poor clinical outcome (modified Rankin Scale score >=4) according to the variables of interest. RESULTS: Prodromal minor stroke was associated with poor outcome (crude risk ratio [cRR], 1.26; 95% CI, 1.12-1.42), but TIAs were not (cRR, .93; 95% CI, .79-1.09). These associations remained essentially the same after adjustment for confounding variables. CONCLUSIONS: Prodromal minor stroke was associated with an unfavorable outcome in patients with basilar artery occlusion, whereas prodromal TIA was not. PMID- 26153509 TI - Electrocardiographic and Echocardiographic Left Ventricular Hypertrophy in the Prediction of Stroke in the Elderly. AB - INTRODUCTION: It is unclear whether left ventricular hypertrophy (LVH) detected by electrocardiography (ECG-LVH) is equally predictive of heart failure as LVH detected by echocardiography (echo-LVH). METHODS: This analysis included 4,008 white participants (41% men) aged 65 years or older from the Cardiovascular Health Study who were free of stroke and major intraventricular conduction defects. ECG-LVH was defined by the Cornell criteria from baseline ECG data and echo-LVH was calculated from baseline echocardiography measurements. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ECG-LVH and echo-LVH and adjudicated incident stroke events, separately. Harrell's concordance indices (C-index) were calculated for the Framingham Stroke Risk Score with inclusion of ECG-LVH and echo-LVH, separately. RESULTS: ECG-LVH was detected in 136 (3.4%) participants and echo-LVH was present in 208 (5.2%) participants. Over a median follow-up of 13 years, a total of 769 (19%; incidence rate = 15.4 per 1000 person-years) strokes occurred. In a multivariable Cox regression analysis adjusted for stroke risk factors and potential confounders, ECG-LVH (HR = 1.68; 95% CI = 1.23, 2.28) and echo-LVH (HR = 1.58; 95% CI = 1.17, 2.14) were associated with an increased risk of stroke. Similar values were obtained for the C-index when either ECG-LVH (C-index = .786) or echo-LVH (C-index = .786) were included in the Framingham Stroke Risk Score. CONCLUSION: ECG-LVH and echo-LVH are able to be used interchangeably in stroke risk scores. PMID- 26153510 TI - Protocol for Cerebral Microbleeds during the Non-Vitamin K Antagonist Oral Anticoagulants or Warfarin Therapy in Stroke Patients with Nonvalvular Atrial Fibrillation (CMB-NOW) Study: Multisite Pilot Trial. AB - RATIONALE: Anticoagulants are widely used to prevent recurrence of ischemic stroke in patients with nonvalvular atrial fibrillation, but in some patients, they also cause bleeding, particularly intracranial hemorrhage. One of the independent predictors of intracerebral hemorrhage is the presence of cerebral microbleeds (CMBs); a high incidence of intracerebral hemorrhage is reported in warfarin-treated patients with multiple CMBs. Longitudinal study suggested that the presence of CMBs at baseline is a predictor of new CMBs in warfarin-treated patients. However, there has been no study on the progression of CMBs in patients receiving the non-vitamin K antagonist oral anticoagulants (NOACs). AIMS: This study tests the hypothesis that the incidence of hemorrhagic stroke is lower in patients receiving NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) than in those receiving warfarin, and this difference reflects the difference in the effects of warfarin and NOACs on the progression of CMBs. DESIGN: We will enroll 200 patients with at least 1 CMB detected by 1.5 T magnetic resonance imaging (T2(*)-weighted imaging) at baseline and who have received NOACs or warfarin for at least 12 months. Primary end point is the proportion of subjects with an increased number of CMBs at month 12 of treatment with NOACs or warfarin. If the results of this study support the efficacy of NOACs for preventing increase of CMBs, this would be of great interest to domestic and overseas clinicians, in view of the potential therapeutic impact, including that on primary prevention of ischemic stroke. PMID- 26153511 TI - Similar chemokine receptor profiles in lymphomas with central nervous system involvement - possible biomarkers for patient selection for central nervous system prophylaxis, a retrospective study. AB - Central nervous system (CNS) relapse occurs in around 5% of diffuse large B-cell lymphoma (DLBCL) cases. No biomarkers to identify high-risk patients have been discovered. We evaluated the expression of lymphocyte-guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi-square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL. PMID- 26153512 TI - Current status and prospects of computational resources for natural product dereplication: a review. AB - Research in natural products has always enhanced drug discovery by providing new and unique chemical compounds. However, recently, drug discovery from natural products is slowed down by the increasing chance of re-isolating known compounds. Rapid identification of previously isolated compounds in an automated manner, called dereplication, steers researchers toward novel findings, thereby reducing the time and effort for identifying new drug leads. Dereplication identifies compounds by comparing processed experimental data with those of known compounds, and so, diverse computational resources such as databases and tools to process and compare compound data are necessary. Automating the dereplication process through the integration of computational resources has always been an aspired goal of natural product researchers. To increase the utilization of current computational resources for natural products, we first provide an overview of the dereplication process, and then list useful resources, categorizing into databases, methods and software tools and further explaining them from a dereplication perspective. Finally, we discuss the current challenges to automating dereplication and proposed solutions. PMID- 26153513 TI - Joint symptoms and health-related quality of life in postmenopausal women with breast cancer who completed 5 years of anastrozole. AB - PURPOSE: To assess the joint symptoms and the impact on patients' health-related quality of life (HRQOL) due to 5 years of anastrozole from the baseline data in the N-SAS BC 05 trial, a randomized clinical trial was designed to assess the efficacy of 5 additional years of anastrozole among women with breast cancer. METHODS: Joint symptoms and HRQOL were evaluated using an original questionnaire for joint symptoms, the Short Form 36-item Health Survey (SF-36), the EuroQol EQ 5D-3L, and a subscale of the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES). RESULTS: Baseline joint symptom and HRQOL data were collected from 330 patients between November 2007 and March 2010. Joint pain and joint stiffness were reported by 61.6 and 59.1 % of patients, respectively, although these symptoms did not affect the activities of daily living in 96.0 and 97.9 % of patients, respectively. Joint pain was reported in the knee by 61.0 % of patients and in the hand by 36.0 % of patients. Joint stiffness mainly affected the hand (67.9 %), especially the proximal interphalangeal joint, and typically occurred upon waking up or in the morning. Most SF-36 domains had good average scores, although slight decreases in physical functioning and role-physical were observed (compared to the national standard scores). The mean EQ-5D utility score was 0.86, and the total FACT-ES subscale score was 62.2/76. CONCLUSIONS: After 5 years of anastrozole, many of the patients reported joint pain and stiffness in mainly the hand and knee with mild symptoms and good HRQOL. PMID- 26153514 TI - Recurrent Clostridium difficile infection and the microbiome. AB - The diverse and densely populated gastrointestinal microbiota is essential for the regulation of host physiology and immune function. As our knowledge of the composition and function of the intestinal microbiota continues to expand, there is new interest in using these developments to tailor fecal microbiota transplantation (FMT) and microbial ecosystem therapeutics (MET) for a variety of diseases. The potential role of FMT and MET in the treatment of Clostridium difficile infection (CDI)-currently the leading nosocomial gastrointestinal infection-has proven highly effective for recurrent CDI, and has emerged as a paradigm shift in the treatment of this disease. The current review will serve as a summary of the key aspects of CDI, and will introduce the essential framework and challenges of FMT, as is currently practiced. MET represents the progression of conventional bacteriotherapy that fundamentally capitalizes on the restorative properties of intestinal bacterial communities and may be viewed as the culmination of a rationally designed therapeutic modality. As our understanding of the composition and function of the intestinal microbiota evolves, it will likely drive next-generation microbiota therapies for a range of medical conditions, such as inflammatory bowel disease, obesity, and metabolic syndrome. PMID- 26153515 TI - LayerCake: a tool for the visual comparison of viral deep sequencing data. AB - MOTIVATION: The advent of next-generation sequencing (NGS) has created unprecedented opportunities to examine viral populations within individual hosts, among infected individuals and over time. Comparing sequence variability across viral genomes allows for the construction of complex population structures, the analysis of which can yield powerful biological insights. However, the simultaneous display of sequence variation, coverage depth and quality scores across thousands of bases presents a unique visualization challenge that has not been fully met by current NGS analysis tools. RESULTS: Here, we present LayerCake, a self-contained visualization tool that allows for the rapid analysis of variation in viral NGS data. LayerCake enables the user to simultaneously visualize variations in multiple viral populations across entire genomes within a highly customizable framework, drawing attention to pertinent and interesting patterns of variation. We have successfully deployed LayerCake to assist with a variety of different genomics datasets. AVAILABILITY AND IMPLEMENTATION: Program downloads and detailed instructions are available at http://graphics.cs.wisc.edu/WP/layercake under a modified MIT license. LayerCake is a cross-platform tool written in the Processing framework for Java. CONTACT: mcorrell@cs.wisc.edu. PMID- 26153516 TI - Injuries in women's international ice hockey: an 8-year study of the World Championship tournaments and Olympic Winter Games. AB - BACKGROUND: We report the incidence, type, mechanism and severity of ice hockey injuries in women's international ice hockey championships. METHODS: All injuries in the International Ice Hockey Federation World Women's Championship, World Women's under-18 Championship and Olympic Winter Games tournaments were analysed over an 8-year period using a strict injury definition, standardised reporting and team physician diagnosis. RESULTS: 168 injuries were recorded in 637 games over an 8-year period resulting in an injury rate (IR) of 6.4 per 1000 player games and 22.0/1000 player-game hours. The IRs were 2.7/1000 player-games for the lower body, 1.4 for the upper body, 1.3 for the head and face and 0.9 for the spine and trunk. Contusion was the most common injury followed by a sprain. The most commonly injured site was the knee (48.6% of lower body injuries; IR 1.3/1000 player-games). The Medial collateral ligament sprain occurred in 37.1% and ACL rupture in 11.4% of knee injuries. A concussion (74.3%; IR 1.0/1000 player-games) was the most common head injury. CONCLUSIONS AND RECOMMENDATIONS: The risk of injury to female ice hockey players at World Championship and Olympic tournaments was about half of that observed in the men's Championships. Full facial protection decreases the risk of lacerations and should be continued in all future female tournaments. More effective prevention strategies for knee, ankle and shoulder injuries are needed in women's ice hockey. Improved concussion education is necessary to promote more consistent diagnosis and return to play protocols. PMID- 26153517 TI - Silicon micromachined ultrasonic scalpel for the dissection and coagulation of tissue. AB - This work presents a planar, longitudinal mode ultrasonic scalpel microfabricated from monocrystalline silicon wafers. Silicon was selected as the material for the ultrasonic horn due to its high speed of sound and thermal conductivity as well as its low density compared to commonly used titanium based alloys. Combined with a relatively high Young's modulus, a lighter, more efficient design for the ultrasonic scalpel can be implemented which, due to silicon batch manufacturing, can be fabricated at a lower cost. Transverse displacement of the piezoelectric actuators is coupled into the planar silicon structure and amplified by its horn like geometry. Using finite element modeling and experimental displacement and velocity data as well as cutting tests, key design parameters have been identified that directly influence the power efficiency and robustness of the device as well as its ease of controllability when driven in resonance. Designs in which the full- and half-wave transverse modes of the transducer are matched or not matched to the natural frequencies of the piezoelectric actuators have been evaluated. The performance of the Si micromachined scalpels has been found to be comparable to existing commercial titanium based ultrasonic scalpels used in surgical operations for efficient dissection of tissue as well as coaptation and coagulation of tissue for hemostasis. Tip displacements (peak-to-peak) of the scalpels in the range of 10-50 MUm with velocities ranging from 4 to 11 m/s have been achieved. The frequency of operation is in the range of 50-100 kHz depending on the transverse operating mode and the length of the scalpel. The cutting ability of the micromachined scalpels has been successfully demonstrated on chicken tissue. PMID- 26153518 TI - Evaluation of cholesterol metabolism in cerebrotendinous xanthomatosis. AB - BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a treatable bile acid disorder caused by mutations of CYP27A1. The pathogenesis of neurological damage has not been completely explained. Oral chenodeoxycholic acid (CDCA) can lead to clinical stabilization, but in a subgroup of patients the disease progresses despite treatment. In the present study, we aimed at clarifying cholesterol metabolism abnormalities and their response to CDCA treatment, in order to identify reliable diagnostic and prognostic markers and understand if differences exist between stable patients and those with neurological progression. METHODS: We enrolled 19 untreated CTX patients and assessed serum profile of bile acids intermediates, oxysterols, cholesterol, lathosterol, and plant sterols. Then we performed a long-term follow up during CDCA therapy, and compared biochemical data with neurological outcome. RESULTS: We observed increase of cholestanol, 7alpha-hydroxy-4-cholesten-3-one (7alphaC4), lathosterol, and plant sterols, whereas 27-hydroxycholesterol (27-OHC) was extremely low or absent. CDCA treatment at a daily dose of 750 mg normalized all biochemical parameters except for 7alphaC4 which persisted slightly higher than normal in most patients, and 27 OHC which was not modified by therapy. Biochemical evaluation did not reveal significant differences between stable and worsening patients. DISCUSSION: Cholestanol and 7alphaC4 represent important markers for CTX diagnosis and monitoring of therapy. Treatment with CDCA should aim at normalizing serum 7alphaC4 as well as cholestanol, since 7alphaC4 better mirrors 7alpha hydroxylation rate and is thought to be correlated with cholestanol accumulation in the brain. Assessment of serum 27-OHC is a very good tool for biochemical diagnosis at any stage of disease. Lathosterol and plant sterols should be considered as additional markers for diagnosis and monitoring of therapy. Further studies including long-term assessment of bile acid intermediates in cerebrospinal fluid are needed in patients who show clinical progression despite treatment. PMID- 26153519 TI - NF-kappaB and AKT signaling prevent DNA damage in transformed pre-B cells by suppressing RAG1/2 expression and activity. AB - In developing lymphocytes, expression and activity of the recombination activation gene protein 1 (RAG1) and RAG2 endonuclease complex is tightly regulated to ensure ordered recombination of the immunoglobulin genes and to avoid genomic instability. Aberrant RAG activity has been implicated in the generation of secondary genetic events in human B-cell acute lymphoblastic leukemias (B-ALLs), illustrating the oncogenic potential of the RAG complex. Several layers of regulation prevent collateral genomic DNA damage by restricting RAG activity to the G1 phase of the cell cycle. In this study, we show a novel pathway that suppresses RAG expression in cycling-transformed mouse pre-B cells and human pre-B B-ALL cells that involves the negative regulation of FOXO1 by nuclear factor kappaB (NF-kappaB). Inhibition of NF-kappaB in cycling pre-B cells resulted in upregulation of RAG expression and recombination activity, which provoked RAG-dependent DNA damage. In agreement, we observe a negative correlation between NF-kappaB activity and the expression of RAG1, RAG2, and TdT in B-ALL patients. Our data suggest that targeting NF-kappaB in B-ALL increases the risk of RAG-dependent genomic instability. PMID- 26153520 TI - The polyphosphate-factor XII pathway drives coagulation in prostate cancer associated thrombosis. AB - Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that colocalized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies. PMID- 26153521 TI - Lesion of medullary catecholaminergic neurons is associated with cardiovascular dysfunction in rotenone-induced Parkinson's disease rats. AB - In recent years, non-motor symptoms have been recognised as of vital importance in Parkinson's disease (PD); among these, cardiovascular dysfunctions are commonly seen in PD patients before their motor signs. The role of cardiovascular dysfunction in the progression of PD pathology, and its underlying mechanisms, are largely unknown. In the present study, in rotenone-induced PD rats, there was a gradual reduction in the number of nigral tyrosine hydroxylase-immunoreactive (TH-ir) neurons after 7, 14 and 21 days treatment. With the 56% reduction in striatal dopamine content and 52% loss of TH-ir neurons on the 14th day, the rats showed motor dysfunctions. However, from ECG power spectra, reductions in normalised low-frequency power and in the low-frequency power : high-frequency power ratio, as well as in mean blood pressure, were observed as early as the 3rd day. Plasma norepinephrine (NE) and epinephrine (E) levels were decreased by 39% and 26% respectively at the same time. Pearson's correlation analysis showed that both plasma NE and plasma E levels were positively correlated with MBP. Our results also showed that the loss of catecholaminergic neurons in the rostral ventrolateral medulla (RVLM), but not in the caudal ventrolateral medulla or the nucleus tractus solitarii, emerged earlier than the loss of nigral dopaminergic neurons. This suggests that dysfunction of catecholaminergic neurons in the RVLM might account for the reduced sympathetic activity, MBP and plasma catecholamine levels in the early stages of PD. PMID- 26153523 TI - Creep and flow of glasses: strain response linked to the spatial distribution of dynamical heterogeneities. AB - Mechanical properties are of central importance to materials sciences, in particular if they depend on external stimuli. Here we investigate the rheological response of amorphous solids, namely colloidal glasses, to external forces. Using confocal microscopy and computer simulations, we establish a quantitative link between the macroscopic creep response and the microscopic single-particle dynamics. We observe dynamical heterogeneities, namely regions of enhanced mobility, which remain localized in the creep regime, but grow for applied stresses leading to steady flow. These different behaviors are also reflected in the average particle dynamics, quantified by the mean squared displacement of the individual particles, and the fraction of active regions. Both microscopic quantities are found to be proportional to the macroscopic strain, despite the non-equilibrium and non-linear conditions during creep and the transient regime prior to steady flow. PMID- 26153522 TI - Intravascular ultrasound and optical coherence tomography imaging of coronary atherosclerosis. AB - Invasive imaging modalities, in particular intravascular ultrasound (IVUS) and optical coherence tomography (OCT), have become established tools for the in vivo study of coronary atherosclerosis. Their use in clinical studies has confirmed histopathological observations that certain important plaque features, such as thin fibrous caps and large lipid cores, are associated with plaque rupture, the precipitating event for the majority of myocardial infarctions. Serial imaging studies have also successfully been used for the evaluation of potential disease modifying pharmacological agents. Recent prospective IVUS studies have confirmed specific baseline imaging features associated with subsequent adverse clinical outcomes, although absolute event rates were too low for clinical utility. Development of hybrid IVUS-OCT imaging or integration of novel techniques, including near-infrared spectroscopy, plaque structural and endothelial shear stress, have great potential to improve our current ability to identify and stratify atheromatous plaques at risk of rupture. PMID- 26153525 TI - Role of exosomes and microvesicles in hypoxia-associated tumour development and cardiovascular disease. AB - Exosomes and microvesicles, collectively referred to as extracellular vesicles (EVs), can transfer complex biological information and induce a diverse signalling response in recipient cells with potential relevance in a wide array of pathological conditions. Tissue hypoxia constitutes a stress-associated phenotype that is central to the malignant state of aggressive tumours as well as to ischaemic tissue in cardiovascular disorders. The adaptive response to hypoxic stress is largely dependent on intercellular communication in which EVs, and cellular exchange of EV cargo molecules, have recently been implicated. The results of numerous studies indicate that hypoxia-dependent shaping of the molecular profile of EVs may mediate the biological response to hypoxia. EVs have been shown to induce tumour angiogenesis and hypercoagulation as well as tissue remodelling and protective effects in ischaemic cardiovascular conditions. Recent findings report increased levels of circulating EVs in patients with hypoxia associated disorders such as myocardial infarction, stroke and pre-eclampsia, indicating a role of EVs as biomarkers in these pathophysiological states. Here, we discuss the intriguing role of EVs in tumour development and cardiovascular disease, focusing on the paracrine transfer of the hypoxic response to neighbouring cells and to distant cells at the systemic level, with wide implications for biomarker discovery and therapeutic intervention. PMID- 26153524 TI - Involvement of PKA and ERK pathways in ghrelin-induced long-lasting potentiation of excitatory synaptic transmission in the CA1 area of rat hippocampus. AB - Acute effects of ghrelin on excitatory synaptic transmission were evaluated on hippocampal CA1 synapses. Ghrelin triggered an enduring enhancement of synaptic transmission independently of NMDA receptor activation and probably via postsynaptic modifications. This ghrelin-mediated potentiation resulted from the activation of GHS-R1a receptors as it was mimicked by the selective agonist JMV1843 and blocked by the selective antagonist JMV2959. This potentiation also required the activation of PKA and ERK pathways to occur as it was inhibited by KT5720 and U0126, respectively. Moreover it most probably involved Ca(2+) influxes as both ghrelin and JMV1843 elicited intracellular Ca(2+) increases, which were dependent on the presence of extracellular Ca(2+) and mediated by L type Ca(2+) channels opening. In addition, ghrelin potentiated AMPA receptor mediated [Ca(2+) ]i increases while decreasing NMDA receptor-mediated ones. Thus the potentiation of synaptic transmission by GHS-R1a at hippocampal CA1 excitatory synapses probably results from postsynaptic mechanisms involving PKA and ERK activation, which are producing long-lasting enhancement of AMPA receptor mediated responses. PMID- 26153526 TI - The impact of dental caries on children and young people: what they have to say? AB - BACKGROUND: Dental caries affects 60-90% of children across the world and is associated with a variety of negative impacts. Despite its ubiquity, there has been surprisingly little exploration of these impacts from the child's perspective. AIM: The aim was to allow children to describe the impact of dental caries on their daily lives and to describe the terminology they used. DESIGN: Children, aged 5-15 years, with caries experience were purposively sampled from primary and secondary care dental clinics. Focus groups (n = 5) and in-depth interviews (n = 16) were recorded and transcribed verbatim. Data analysis took a narrative approach, and themes were derived from the data using framework analysis. RESULTS: Pain was the main theme to emerge. Within this, three subthemes were identified: impacts related to pain, strategies adopted to reduce pain, and emotional aspects resulting from pain. A second theme was also identified relating to the aesthetic aspects of caries. CONCLUSION: Children as young as 5 years of age were able to competently discuss their experiences of dental caries. Participants reported a number of impacts affecting various aspects of their lives. These will be incorporated into the future development of a caries-specific measure of oral health-related quality of life. PMID- 26153527 TI - Storytelling, sugar snacking, and toothbrushing rules: a proposed theoretical and developmental perspective on children's health and oral health literacy. AB - BACKGROUND: Health literacy has been conceptualised to explain how health information facilitates the maintenance of health. What are the clinical implications of children's health literacy? Children have language skills, numeracy, and reading skills that are in a state of flux - how do they decipher and encode adult health messages to make them their own? AIM: To explore children's health and oral health literacy and discover what processes they use to convert adult health messages into useable information. METHODS: Observations and descriptive case study approach. RESULTS: A theoretical and developmental perspective on children's health and oral health literacy, based upon the ability of the adult to provide a health message with a common shared element, is proposed. It is this common element that the child uses to make adult words understandable and to generate health action. CONCLUSIONS: Children's health and oral health literacy development is achieved, through, a torturous path, supported by the way adults provide health messages to children. Taking time to identify this common element, helping children to encode and reflect upon the health message will help children convert adult oral health messages into their own oral health practices, and support their emerging health and oral health literacy. PMID- 26153528 TI - Mitochondrial DNA variation of Nigerian domestic helmeted guinea fowl. AB - We analyzed genetic diversity of 215 mitochondrial DNA (mtDNA) D-loop sequences from seven populations of domesticated helmeted guinea fowl (Numida meleagris) in Nigeria and compared that with results of samples collected in Kenya (n = 4) and China (n = 22). In total, 241 sequences were assigned to 22 distinct haplotypes. Haplotype diversity in Nigeria was 0.693 +/- 0.022. The network grouped most matrilines into two main haplogroups: A and B. There was an absence of a geographic signal, and two haplotypes dominated across all locations with the exception of the Kebbi population in the northwest of the country; AMOVA also confirmed this observation (FST = 0.035). The low genetic diversity may be a result of recent domestication, whereas the lack of maternal genetic structure likely suggests the extensive genetic intermixing within the country. Additionally, the differentiation of the Kebbi population may be due to a certain demographic history and/or artificial selection that shaped its haplotype profile. The current data do not permit us to make further conclusions; therefore, more research evidence from genetics and archaeology is still required. PMID- 26153529 TI - Transcriptome comparison in the pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure. AB - Chronic stress can induce a series of maladjustments, and the response to stress is partly regulated by the hypothalamus-pituitary-adrenal axis. The aim of this study was to investigate the genetic mechanisms of this axis regulating stress responsiveness. The pituitary and adrenal cortex of Beagle and Chinese Field Dog (CFD) from a stress exposure group [including Beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), Beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)] and a control group [including Beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), Beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)], selected to perform RNA-seq transcriptome comparisons, showed that 40, 346, 376, 69, 70, 38, 57 and 71 differentially expressed genes were detected in BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1, BP2 vs. CFDP2, BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2 respectively. NPB was a gene common to BAC1 vs. BAC2 and CFDAC1 vs. CFDAC2, indicating it was a potential gene affecting response to chronic stress, regardless of the extent of chronic stress induced. PLP1 was a gene common to BP1 vs. CFDP1 and BP2 vs. CFDP2, suggesting its important roles in affecting the stress-tolerance difference between the two breeds, regardless of whether there was stress exposure or not. Pathway analysis found 12, 4, 11 and 1 enriched pathway in the comparisons of BP1 vs. CFDP1, BP2 vs. CFDP2, CFDP1 vs. CFDP2 and BAC1 vs. BAC2 respectively. Glutamatergic synapse, neuroactive ligand-receptor interaction, retrograde endocannabinoid signaling, GABAergic synapse, calcium signaling pathway and dopaminergic synapse were the most significantly enriched pathways in both CFDP1 vs. CFDP2 and BP1 vs. CFDP1. GO, KEGG pathway and gene network analysis demonstrated that GRIA3, GRIN2A, GRIN2B and NPY were important in regulating the stress response in CFD. Nevertheless, ADORA1, CAMK2A, GRM1, GRM7 and NR4A1 might be critical genes contributing to the stress-tolerance difference between CFD and Beagle when subjected to stress exposure. In addition, RGS4 and SYN1 might play important roles both in regulating the stress response in CFD and in affecting the stress tolerance difference in different breeds. These observations clearly showed that some genes in the adrenal cortex and pituitary could regulate the stress response in Beagle and CFDs, whereas some others could affect the stress-tolerance difference between these two breeds. Our results can contribute to a more comprehensive understanding of the genetic mechanisms of response to chronic stress. PMID- 26153530 TI - Study of Protein Expression in Peri-Infarct Tissue after Cerebral Ischemia. AB - In this work, we report our study of protein expression in rat peri-infarct tissue, 48 h after the induction of permanent focal cerebral ischemia. Two proteomic approaches, gel electrophoresis with mass spectrometry and combined fractional diagonal chromatography (COFRADIC), were performed using tissue samples from the periphery of the induced cerebral ischemic lesions, using tissue from the contra-lateral hemisphere as a control. Several protein spots (3408) were identified by gel electrophoresis, and 11 showed significant differences in expression between peri-infarct and contra-lateral tissues (at least 3-fold, p < 0.05). Using COFRADIC, 5412 proteins were identified, with 72 showing a difference in expression. Apart from blood-related proteins (such as serum albumin), both techniques showed that the 70 kDa family of heat shock proteins were highly expressed in the peri-infarct tissue. Further studies by 1D and 2D western blotting and immunohistochemistry revealed that only one member of this family (the inducible form, HSP72 or HSP70i) is specifically expressed by the peri-infarct tissue, while the majority of this family (the constitutive form, HSC70 or HSP70c) is expressed in the whole brain. Our data support that HSP72 is a suitable biomarker of peri-infarct tissue in the ischemic brain. PMID- 26153531 TI - Electrical stimulation therapy of the lower oesophageal sphincter for refractory gastro-oesophageal reflux disease - interim results of an international multicentre trial. AB - BACKGROUND: A previous single-centre study showed that lower oesophageal sphincter electrical stimulation therapy (LES-EST) in gastro-oesophageal reflux disease (GERD) patients improves reflux symptoms and decreases oesophageal acid exposure. AIM: To evaluate safety and efficacy of LES-EST in GERD patients with incomplete response to proton pump inhibitors (PPIs) in a prospective, international, multicentre, open-label study. METHODS: GERD patients, partially responsive to PPIs, received LES-EST. GERD health-related quality of life (GERD HRQL), daily symptom diaries, quality of life scores, oesophageal acid exposure, and LES resting and residual pressure were measured before and after initiation of LES-EST. Stimulation sessions were optimised based on residual symptoms and oesophageal acid exposure. RESULTS: Forty-four patients were enrolled and 6-month data from 41 patients are available. Hiatal repair was performed in 16 patients. One device-related, one procedure-related and one unrelated severe adverse event were reported. GERD-HRQL improved from 31.0 (IQR 26.2-36.8) off-PPI and 16.5 (IQR 9.0-22.8) on-PPI to 4 (IQR 1-8) at 3-month and 5 (IQR 3-9) at 6-month follow-up (P < 0.0001 vs. on- and off-PPI). Oesophageal acid exposure (pH < 4.0) improved from 10.0% (IQR 7.5-12.9) to 3.8% (IQR 1.9-12.3) at 3 months (P = 0.0027) and 4.4% (IQR 2.2-7.2) at 6 months (P < 0.0001). CONCLUSIONS: These interim results show an acceptable safety record of LES-EST to date, combined with good short term efficacy in GERD patients who are partially responsive to PPI therapy. A remarkable reduction in regurgitation symptoms, without the risk of intervention requiring dysphagia may prove to be an advantage compared with other anti-reflux procedures. ClinicalTrials.gov Identifier: NCT01574339. PMID- 26153532 TI - Feeding on Beauveria bassiana-treated Frankliniella occidentalis causes negative effects on the predatory mite Neoseiulus barkeri. AB - The entomopathogenic fungus Beauveria bassiana and the predatory mite Neoseiulus barkeri are both potential biocontrol agents for their shared host/prey Frankliniella occidentalis. The combination of the two agents may enhance biological control of F. occidentalis if the fungus does not negatively affect N. barkeri. This study evaluated the indirect effects of B. bassiana strain SZ-26 on N. barkeri mediated by F. occidentalis using the age-stage, two-sex life table. When fed on the first instar larvae of F. occidentalis that had been exposed for 12 h to the SZ-26 suspension, the developmental time of preadult N. barkeri was significantly longer, and the longevity and fecundity were significantly lower than that of N. barkeri fed on untreated F. occidentalis. The mean generation time (T), net reproductive rate (R0), finite rate of increase (lambda), intrinsic rate of natural increase (rm) and predation rates were correspondingly affected. The data showed that B. bassiana has indirect negative effects on N. barkeri population dynamics via influencing their prey F. occidentalis larvae, which indicates that there is a risk in combining B. bassiana with N. barkeri simultaneously for the biocontrol of F. occidentalis. The probable mechanism for the negative effects is discussed. PMID- 26153533 TI - High quality thin films of thermoelectric misfit cobalt oxides prepared by a chemical solution method. AB - Misfit cobaltates ([Bi/Ba/Sr/Ca/CoO]n(RS)[CoO2]q) constitute the most promising family of thermoelectric oxides for high temperature energy harvesting. However, their complex structure and chemical composition makes extremely challenging their deposition by high-vacuum physical techniques. Therefore, many of them have not been prepared as thin films until now. Here we report the synthesis of high quality epitaxial thin films of the most representative members of this family of compounds by a water-based chemical solution deposition method. The films show an exceptional crystalline quality, with an electrical conductivity and thermopower comparable to single crystals. These properties are linked to the epitaxial matching of the rock-salt layers of the structure to the substrate, producing clean interfaces free of amorphous phases. This is an important step forward for the integration of these materials with complementary n-type thermoelectric oxides in multilayer nanostructures. PMID- 26153534 TI - The elusive life cycle of scyphozoan jellyfish--metagenesis revisited. AB - Massive proliferations of scyphozoan jellyfish considerably affect human industries and irreversibly change food webs. Efforts to understand the role of jellyfish in marine ecosystems are based on a life cycle model described 200 years ago. According to this paradigm the pelagic medusae is considered seasonal and alternates with the benthic polyp stage from which it derives. However, we provide evidence that a) the occurrence of several species of medusae is not restricted to a season in the year, they overwinter, b) polyp- and medusa generations are neither temporally nor spatially separated, and c) "metagenesis" which is defined as the alternation between sexual and asexual generations does not always occur. Hence we recommend additions to the current model and argue that the scyphozoan life cycle should be considered multi-modal, rather than metagenetic. The implications of these findings for jellyfish proliferations, including possible consequences and associated environmental drivers, are discussed. PMID- 26153535 TI - How ants use quorum sensing to estimate the average quality of a fluctuating resource. AB - We show that one of the advantages of quorum-based decision-making is an ability to estimate the average value of a resource that fluctuates in quality. By using a quorum threshold, namely the number of ants within a new nest site, to determine their choice, the ants are in effect voting with their feet. Our results show that such quorum sensing is compatible with homogenization theory such that the average value of a new nest site is determined by ants accumulating within it when the nest site is of high quality and leaving when it is poor. Hence, the ants can estimate a surprisingly accurate running average quality of a complex resource through the use of extraordinarily simple procedures. PMID- 26153536 TI - Increment of Access Points in Integrated System of Wavelength Division Multiplexed Passive Optical Network Radio over Fiber. AB - This paper describes a novel technique to increase the numbers of access points (APs) in a wavelength division multiplexed-passive optical network (WDM-PON) integrated in a 100 GHz radio-over-fiber (RoF). Eight multi-carriers separated by 25 GHz intervals were generated in the range of 193.025 to 193.200 THz using a microring resonator (MRR) system incorporating an add-drop filter system. All optically generated multi-carriers were utilized in an integrated system of WDM PON-RoF for transmission of four 43.6 Gb/sec orthogonal frequency division multiplexing (OFDM) signals. Results showed that an acceptable BER variation for different path lengths up to 25 km was achievable for all four access points and thus the transmission of four OFDM channels is feasible for a 25 km standard single mode fiber (SSMF) path length. PMID- 26153537 TI - The effect of an integrated syndromic respiratory disease guideline in primary health care settings. AB - RATIONALE, AIMS AND OBJECTIVES: The use of integrated syndromic guidelines (ISG) aims to improve the quality of care for patients with respiratory diseases. The impact of such ISG in clinical practice can be potentially significant in primary health care (PHC) settings. We report the impact of the use by general practitioners (GPs) of a Tunisian ISG for respiratory diseases in management of respiratory patients in PHC. METHODS: The short-term impact was assessed through the results of the feasibility study. This study included a baseline survey, before training on ISG, and an impact survey, after training on ISG. The same 73 GPs practicing within 28 PHCs were involved in the two surveys at an interval of 6 weeks. Information on each patient mentioned gender, age, underlying conditions, symptoms, referral, diagnosis and drug prescription details. RESULTS: During the periods of the baseline and impact surveys, 36.0 and 31.1% of PHC attendees, respectively, sought care for respiratory symptoms. Acute respiratory infection (ARI) cases accounted for more than 85% of patients with respiratory disease. In the impact survey, chronic respiratory disease (CRD) diagnosis increased by approximately 50%. In the same way, the proportion of tuberculosis suspects increased 5.5 times. The number of drugs prescribed per patient decreased by 18.8%, and the proportion of patients who were prescribed antibiotics decreased by 19.0%. The prescription of steroids also significantly decreased while inhaled beta-agonist prescription increased. The average cost of drug prescription was reduced by 19%. CONCLUSION: Training on ISG for respiratory diseases improved the diagnosis of CRD and tuberculosis, and lead to a more rational use of drugs for ARIs in PHCs. PMID- 26153538 TI - Efficient production of T cells from mouse pluripotent stem cells by controlled expression of Lhx2. AB - LIM-homeobox transcription factor Lhx2 induces ex vivo amplification of adult hematopoietic stem cells (HSCs) in mice. We previously showed that engraftable HSC-like cells are generated from mouse embryonic stem cells (ESCs) and induced pluripotent stem cells by enforced expression of Lhx2. However, when these HSC like cells were transplanted into irradiated congenic mice, donor-derived T cells were barely detectable, whereas other lineages of hematopoietic cells were continuously produced. Here we investigated T-cell differentiation potential of the Lhx2-induced HSC-like cells using ESCs carrying doxycycline (dox)-inducible Lhx2 expression cassette. Dox-mediated over-expression of Lhx2 conferred a self renewing activity to ESC-derived c-Kit(+) CD41(+) embryonic hematopoietic progenitor cells (HPCs), thereby converting them to HSC-like cells. When these HSC-like cells were transplanted into irradiated immunodeficient mice and they were supplied with a dox-containing water, CD4/8 double negative T cells were detected in their thymi. Once the Lhx2 expression was terminated, differentiation of CD4/8 double positive and single positive T cells was initiated in the thymi of transplanted mice and mature T cells were released in the peripheral blood. These results showed that engraftable HSC-like cells with full hematopoietic potential can be obtained from ESCs by the conditional expression of Lhx2. PMID- 26153539 TI - Quantitative structure-activity relationship correlation between molecular structure and the Rayleigh enantiomeric enrichment factor. AB - It was recently demonstrated that under environmentally relevant conditions the Rayleigh equation is valid to describe the enantiomeric enrichment - conversion relationship, yielding a proportional constant called the enantiomeric enrichment factor, epsilonER. In the present study we demonstrate a quantitative structure activity relationship model (QSAR) that describes well the dependence of epsilonER on molecular structure. The enantiomeric enrichment factor can be predicted by the linear Hansch model, which correlates biological activity with physicochemical properties. Enantioselective hydrolysis of sixteen derivatives of 2-(phenoxy)propionate (PPMs) have been analyzed during enzymatic degradation by lipases from Pseudomonas fluorescens (PFL), Pseudomonas cepacia (PCL), and Candida rugosa (CRL). In all cases the QSAR relationships were significant with R(2) values of 0.90-0.93, and showed high predictive abilities with internal and external validations providing QLOO(2) values of 0.85-0.87 and QExt(2) values of 0.8-0.91. Moreover, it is demonstrated that this model enables differentiation between enzymes with different binding site shapes. The enantioselectivity of PFL and PCL was dictated by electronic properties, whereas the enantioselectivity of CRL was determined by lipophilicity and steric factors. The predictive ability of the QSAR model demonstrated in the present study may serve as a helpful tool in environmental studies, assisting in source tracking of unstudied chiral compounds belonging to a well-studied homologous series. PMID- 26153540 TI - [Reliability of Primary Care computerised medication records]. AB - OBJECTIVE: To quantify and to evaluate the reliability of Primary Care (PC) computerised medication records of as an information source of patient chronic medications, and to identify associated factors with the presence of discrepancies. DESIGN: A descriptive cross-sectional study. LOCATION: General Referral Hospital in Murcia. PARTICIPANTS: Patients admitted to the cardiology chest diseases unit, during the months of February to April 2013, on home treatment, who agreed to participate in the study. MAIN MEASUREMENTS: Evaluation of the reliability of Primary Care computerised medication records by analysing the concordance, by identifying discrepancies, between the active medication in these records and that recorded in pharmacist interview with the patient/caregiver. Identification of associated factors with the presence of discrepancies was analysed using a multivariate logistic regression. RESULTS: The study included a total of 308 patients with a mean of 70.9 years (13.0 SD). The concordance of active ingredients was 83.7%, and this decreased to 34.7% when taking the dosage into account. Discrepancies were found in 97.1% of patients. The most frequent discrepancy was omission of frequency (35.6%), commission (drug added unjustifiably) (14.6%), and drug omission (12.7%). Age older than 65 years (1.98 [1.08 to 3.64]), multiple chronic diseases (1.89 [1.04 to 3.42]), and have a narcotic or psychotropic drug prescribed (2.22 [1.16 to 4.24]), were the factors associated with the presence of discrepancies. CONCLUSIONS: Primary Care computerised medication records, although of undoubted interest, are not be reliable enough to be used as the sole source of information on patient chronic medications when admitted to hospital. PMID- 26153541 TI - [Primary health care professionals attitudes towards influenza immunzation in Catalonia]. AB - OBJECTIVE: Health personnel are at risk of acquiring influenza infection and of nosocomial influenza transmission. The objective of this study was to assess the relationship between the knowledge and attitudes of primary care health personnel in Catalonia as regards influenza vaccine and the factors related to the uptake of this vaccine. DESIGN: A cross-sectional study using a web survey. SETTING: Primary care health personnel of the Catalan Health Institute. PARTICIPANTS: A total of 1212 primary health care personnel were included in the survey. Those who had medical reasons for being or not being vaccinated were excluded. RESULTS: A total of 423 replies were valid, with a 46.6% overall vaccination coverage. Vaccination rate was higher among 45 to 54 year-olds, paediatricians, those vaccinated in preceding seasons, and those living with chronic patients. There was an association between having received the vaccine and considering vaccination the best preventive action, advocating vaccination to at risk population, concern about acquiring influenza, and considering health personnel vaccination important. CONCLUSIONS: Actions taken to increase vaccination rate among health personnel should aim at correcting lack of knowledge and misconceptions about influenza vaccination of health personnel. PMID- 26153542 TI - [Vascular risk in endocrine diseases other than diabetes]. AB - Endocrinological diseases directly affect the cardiovascular system. The deleterious effects on cardiovascular function can be direct, and linked to the increase or reduction of circulating hormones. Equally, the adverse effects may be indirect; for example following the rise in blood pressure, increase or redistribution of lean mass, or increased plasma lipoproteins. The best health care and the increasing availability of biochemical tests lead to the diagnosis of many endocrine diseases before the onset of clinical signs. This review will focus on presenting evidence of cardiovascular functional or structural impairment in cases of primary hyperparathyroidism, Cushing's syndrome, and hypothyroidism in their sub-clinical forms, as well as the reversibility of complications after appropriate treatment. PMID- 26153543 TI - Photochemical production of hydrogen peroxide from natural algicides: decomposition organic matter from straw. AB - The ability of decomposition organic matter from three natural algicides (barley, rice, and wheat straw) and natural organic matter (NOM) isolates to generate hydrogen peroxide under simulated solar irradiation was evaluated in order to understand the mechanism of indirect algae inhibition through a photochemical pathway. Specific optical properties (higher phenolic hydroxyl group contents and lower E2/E3) of barley straw organic matter (BSOM) reveal its outstanding ability to produce H2O2 as a photosensitizer. The appearance of a protein-like structure in BSOM indicated that bacteria or fungi probably transformed the structure of BSOM and brought other organic matter, which may account for its distinct optical properties. The PhiH2O2 of BSOM obtained through aerobic decomposition is 14.73 * 10(-5), which is three times the value of SRHA, whereas the PhiH2O2 value of BSOM obtained for non-aerobic decomposition was 5.30 * 10(-5), still higher than that of SRHA. The PhiH2O2 of rice straw organic matter was slightly lower than those of SRHA and SRFA, but much higher than that of wheat straw organic matter. The superior ability of BSOM to generate H2O2 was partly responsible for the outstanding potential and prior choice of barley straw for cyanobacteria or algae inhibition in various plant decomposition products. PMID- 26153544 TI - The influence of a department's psychosocial climate and treatment environment on cancer patients' anxiety during radiotherapy. AB - PURPOSE: The objective of this study is to determine whether there is a relationship between cancer patients' perceptions of the person-centeredness of their treatment experience and their anxiety levels during treatment. METHOD: A questionnaire was distributed to adult cancer patients going through external beam radiotherapy (RT) with curative intent at a university hospital in Sweden (n = 892), which included two surveys, the State Trait Anxiety Inventory-state specific questions (STAI-S), and the Patient-centered Climate Questionnaire (PCQ) and additional treatment-specific questions. Eligible patients were provided with the questionnaire on their seventh day of RT by an RT-nurse. RESULTS: Statistical analysis showed a significant negative relationship between STAI-S scores and PCQ scores, and a significant positive relationship between the Treatment Environment questions and the STAI-S scores. Multivariate regression modeling found the PCQ subscale of safety to have the strongest negative association with STAI-S scores, showing that a climate of safety can significantly decrease patient situational anxiety levels. On the other hand, difficulty tolerating the overall treatment experience, worry about the treatment equipment, or feelings of isolation or claustrophobia within the treatment room all significantly factor into increases in patient-reported situational anxiety levels. CONCLUSION: Both the treatment environment and the psychosocial climate of the RT clinic significantly impact cancer patient state anxiety levels. These findings suggest that actively employing a person-centered approach during RT, and designing the treatment environment to be more attentive to the patient experience can both play a significant role in decreasing patient situational anxiety during treatment. PMID- 26153545 TI - Brain banks still yield high interest rates. PMID- 26153546 TI - Diagnosis of porcine circovirus type 2 infection with a combination of immunomagnetic beads, single-domain antibody, and fluorescent quantum dot probes. AB - The use of a specific antibody conjugated with nanobeads, forming immunomagnetic nanobeads (IMNBs), has been demonstrated to be useful for the capture and detection of viruses. In this study, IMNBs functionalized with a single-domain antibody against the capsid protein (Cap) of porcine circovirus type 2 (PCV2), hereafter denoted as psdAb, were evaluated and used to capture PCV2. Quantum dots (QDs) conjugated with psdAb were used as a fluorescence probe to visualize PCV2 captured by IMNBs. The specificity and sensitivity of this method were further evaluated using common pathogens of pig viral disease and PCV2. To assess its practicality, clinical samples were tested in this study. The results showed that 2.57 +/- 0.13 mg Cap or 0.97 +/- 0.064 * 10(6) copies of PCV2 particles could be captured by 1 mg of IMNBs in 30 min. This suggests that the IMNBs have the ability to efficiently capture PCV2 with good specificity, as there was no cross reaction with other pathogens, and with strong sensitivity, with a detection limit as low as 10(3) copies/ml of PCV2 particles. Moreover, PCV2 in inguinal lymph node, lung, spleen, serum, and fecal samples was successfully detected by IMNBs. The results demonstrate that this method is promising for the rapid and effective detection of PCV2 in complex clinical samples. PMID- 26153547 TI - Elemental mapping of the entire intact Drosophila gastrointestinal tract. AB - The main role of the animal gastrointestinal (GI) tract is the selective absorption of dietary nutrients from ingested food sources. One class of vital micronutrients are the essential biometals such as copper, zinc and iron, which participate in a plethora of biological process, acting as enzymatic or structural co-factors for numerous proteins and also as important cellular signalling molecules. To help elucidate the mechanisms by which biometals are absorbed from the diet, we mapped elemental distribution in entire, intact Drosophila larval GI tracts using synchrotron X-ray fluorescence microscopy. Our results revealed distinct regions of the GI tract enriched for specific metals. Copper was found to be concentrated in the copper cell region but also in the region directly anterior to the copper cells and unexpectedly, in the middle midgut/iron cell region as well. Iron was observed exclusively in the iron cell region, confirming previous work with iron-specific histological stains. Zinc was observed throughout the GI tract with an increased accumulation in the posterior midgut region, while manganese was seen to co-localize with calcium specifically in clusters in the distal Malpighian tubules. This work simultaneously reveals distribution of a number of biologically important elements in entire, intact GI tracts. These distributions revealed not only a previously undescribed Ca/Mn co localization, but also the unexpected presence of additional Cu accumulations in the iron cell region. PMID- 26153549 TI - Community water fluoridation and health outcomes in England: a cross-sectional study. AB - BACKGROUND: Six million people in England live in areas where the level of fluoride in water is adjusted to reduce the significant public health burden of dental caries. The dental effects of fluoride are well established, but evidence for suggested adverse health effects is limited, with a lack of rigorous small area population studies that control for confounding. This study aims to test the association between water fluoridation schemes and selected health outcomes using the best available routine data sources. METHODS: Ecological level exposure to fluoridated water was estimated for standard small areas and administrative districts in England using Geographical Information Systems and digitized boundaries based on known patterns of water supply. The association between fluoridation and dental and nondental health indicators was tested using multivariable regression models including ecological level confounding variables. Health indicator data were obtained from routine sources. RESULTS: There was strong evidence of lower prevalence of dental caries (P < 0.001) among children living in fluoridated areas, they also had fewer teeth affected on average (P < 0.001), and lower admission rates for tooth extraction (55% lower; 95% CI-73%, 27%; P = 0.001). There was no strong evidence of an association between fluoridation and hip fracture, Down syndrome, all-cancer, all-cause mortality or osteosarcoma. Fluoridation was negatively associated with the incidence of renal stones (7.9% lower; 95% CI-9.6%,-6.2%; P < 0.001) and bladder cancer (8.0% lower; 95% CI-9.9%,-6.0%; P < 0.001). CONCLUSION: This study uses the comprehensive data sets available in England to provide reassurance that fluoridation is a safe and highly effective public health measure to reduce dental decay. Although lower rates of certain nondental outcomes were found in fluoridated areas, the ecological, observational design prohibits any conclusions being drawn regarding a protective role of fluoridation. PMID- 26153548 TI - Adiponectin attenuates liver fibrosis by inducing nitric oxide production of hepatic stellate cells. AB - Adiponectin protects against liver fibrosis, but the mechanisms have not been fully elucidated. Here, we showed that adiponectin upregulated inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) and protein expression in hepatic non parenchymal cells, particularly in hepatic stellate cells (HSCs), and increased nitric oxide (NO2-/NO3-) concentration in HSC-conditioned medium. Adiponectin attenuated HSC proliferation and migration but promoted apoptosis in a NO dependent manner. More advanced liver fibrosis with decreased iNOS/NO levels was observed in adiponectin knockout mice comparing to wide-type mice when administered with CCI4 while NO donor supplementation rescued the phenotype. Further experiments demonstrated that adiponectin-induced iNOS/NO system activation is mediated through adipoR2-AMPK-JNK/Erk1/2-NF-kappaB signaling. These data suggest that adiponectin inhibits HSC function, further limiting the development of liver fibrosis at least in part through adiponectin-induced NO release. Therefore, adiponectin-mediated NO signaling may be a novel target for the treatment of liver fibrosis. KEY MESSAGES: * Adiponectin activates HSC iNOS/NO and SEC eNOS/NO systems. * Adiponectin inhibits HSC proliferation and migration but promotes its apoptosis. * Adiponectin inhibits CCL4-induced liver fibrosis by modulation of liver iNOS/NO. * Adiponectin stimulates HSC iNOS/NO via adipoR2-AMPK-JNK/ErK1/2-NF-kappaB pathway. PMID- 26153550 TI - High-Throughput Cancer Cell Sphere Formation for Characterizing the Efficacy of Photo Dynamic Therapy in 3D Cell Cultures. AB - Photodynamic therapy (PDT), wherein light sensitive non-toxic agents are locally and selectively activated using light, has emerged as an appealing alternative to traditional cancer chemotherapy. Yet to date, PDT efficacy has been mostly characterized using 2D cultures. Compared to 2D cultures, 3D sphere culture generates unique spatial distributions of nutrients and oxygen for the cells that better mimics the in-vivo conditions. Using a novel polyHEMA (non-adherent polymer) fabrication process, we developed a microfluidic sphere formation platform that can (1) generate 1,024 uniform (size variation <10%) cancer spheres within a 2 cm by 2 cm core area, (2) culture spheres for more than 2 weeks, and (3) allow the retrieval of spheres. Using the presented platform, we have successfully characterized the different responses in 2D and 3D cell culture to PDT. Furthermore, we investigated the treatment resistance effect in cancer cells induced by tumor associated fibroblasts (CAF). Although the CAFs can enhance the resistance to traditional chemotherapy agents, no significant difference in PDT was observed. The preliminary results suggest that the PDT can be an attractive alternative cancer therapy, which is less affected by the therapeutic resistance induced by cancer associated cells. PMID- 26153551 TI - Coping as a caregiver: a question of strain and its consequences on life satisfaction and health-related quality of life. AB - A majority of us will at some point in our lives take care of family members, relatives and friends in need of assistance. How will this affect us? Strain related to life satisfaction (LS) and health related quality of life (HRQoL) among caregivers aged 60 years and older has not been previously studied. OBJECTIVES: The main objective was to describe characteristics of non-caregivers (n=2233) and caregivers (n=369). Further objectives were to examine differences in HRQoL and LS between caregivers and non-caregivers, and between caregivers stratified by level of strain. METHODS: We analyzed the differences in socio demographics, social participation, locus of control and symptoms between groups. HRQoL was assessed by Short Form Health Survey (SF-12/PCS and MCS). LS was measured by the Life Satisfaction Index-A (LSI-A). RESULTS: Caregivers were younger, had more years of formal education, more often cohabiting and relied less on powerful others than non-caregivers. One hundred and thirty-three (36%) caregivers reported high strain. In a three-group comparison including non caregivers and caregivers stratified for strain, high strain was associated with lower SF12-PCS, SF12-MCS and LSI-A (0.014, <0.001 and <0.001, respectively). CONCLUSION: High strain affects caregivers' HRQoL and LS in a negative way. PRACTICE: It is important for the health care sector to consider the possibility that symptoms in a person acting as a caregiver can be related to high perceived strain. IMPLICATIONS: A general policy program aiming to identify caregivers and their needs for support is much needed. PMID- 26153552 TI - Development and validation of the health literacy assessment tool for older people in Taiwan: potential impacts of cultural differences. AB - PURPOSE: To screen health literacy among urban elderly in Taiwan, who cannot be evaluated easily using the current measurement tools because of the "face", which meant someone felt embarrassed if he did not know how to do something. MATERIALS AND METHODS: A literature review was performed to define a framework for developing the health literacy screening tool. Two hundred elderly were recruited to test the validity and reliability for pilot study. One thousand and eighty two elderly who came from quota sampling in Taipei City by administrative areas and gender were interviewed face-to-face to gather health literacy performance by the developed health literacy screening tool and the short-form Mandarin Health Literacy Scale (s-MHLS). RESULTS: 10-items of health literacy screening tool by self-perception were developed. The mean score of screening tool among analysis sample was 42.3 (0-50) and s-MHLS was 9.5 (0-11). Pearson correlation coefficient was 0.441 (p<0.0001) between these two measurements. Multiple regressions showed that, female, younger, higher education, living with family, has no primary caregiver, has few medical companionship, and higher score of health knowledge had better health literacy performance in both measurements. CONCLUSIONS: This screening tool should be applied to screen health literacy of elderly came from baby boomer who usually have lower education levels than the general population in Chinese regions. PMID- 26153553 TI - Demographic and socioeconomic inequalities for self-rated health and happiness in elderly: the situation for Turkey regarding World Values Survey between 1990 and 2013. AB - PURPOSE: To define the socioeconomic and demographic determinants for self-rated health and happiness for Turkish elderly (>=60) using the World Values Survey (WVS) database. METHODS: WVS data for Turkey covering 23 years (1990-2013) with five separate cross-sections (1990, 1996, 2001, 2007, 2013) were pooled for analysis (n=870). Dependent variables were self-rated health (SRH) and perception of happiness.Their relation with age, sex, number of children, marital status, income, education, employment status and class perception were evaluated. Chi square and logistic regression analysis were used. Regression coefficients and their standard errors were derived to calculate odds ratios. RESULTS: Mean age was 66.96+/-5.78 (60-91), 58.16% were male and 76.32% were married. The majority (61.10%) was at lowest income level and 80.60% had education attainment at primary level or below. Very happy/quite happy were 81.77% while only 46.59% perceived their health as very good/good. The crisis year (2001) increased the risk of bad self-rated health 4.4 times, being a women 2.0 times, while being a widow had a 2.3-fold, low-income 3.0-fold effect. The odds for unhappy status was increased 4.3 times at low-income levels and 8.4 times for the divorced/separate living partners. Happiness state improved after crisis period. CONCLUSION: SRH and happiness of Turkish elderly bare demographic and socioeconomic inequalities. The inexistence of a partner, being a women, low-income level and major threats for it, like economic crisis, are important drivers for elderly health and happiness. To improve well-being of elderly, better social policies for income is essential and at economic crisis times, support policies should be prioritized for vulnerable groups, including elderly. PMID- 26153554 TI - Prevalence and concentration of Escherichia coli O157 in different seasons and cattle types processed in North America: A systematic review and meta-analysis of published research. AB - Systematic review (SR) and meta-analyses (MA) methodologies were used to identify, critically evaluate and synthesize prevalence and concentration estimates for Escherichia coli O157 contamination along the beef production chain, and to illustrate differences based on cattle types and seasonality in North America from the scientific peer-reviewed literature. Four electronic databases were searched to identify relevant articles. Two independent reviewers performed all SR steps. Random effects MA models were used to estimate the pooled prevalence and concentration of E. coli O157 in feces, hides and carcasses of cattle processed in North America, including their seasonal estimates. The potential sources of between studies heterogeneity were identified using meta regression and sub-group analysis. Results indicated differences in the fecal prevalence of E. coli O157 among cattle types: 10.68% (95% CI: 9.17-12.28%) in fed beef, 4.65% (95% CI: 3.37-6.10%) in adult beef, and 1.79% (95% CI: 1.20 2.48%) in adult dairy. Fed beef fecal prevalence was 10.65% (95% CI: 8.93-12.49%) during summer and 9.17% (95% CI: 5.24-13.98%) during the winter months. For adult beef, the fecal prevalence was 7.86% (95% CI: 5.43-10.66%) during summer, and 4.21% (95% CI: 1.95-7.13%) during winter. Among adult dairy, the fecal prevalence was 2.27% (95% CI: 1.5-3.18%) during summer, and 0.36% (95% CI: 0.09-0.74%) during winter. There was a significantly higher percentage of hides with E. coli O157 concentration >= 40 CFU/100 cm(2) on hides of fed beef sampled at the processing plant (23.81%; 95% CI: 14.79-34.15%) compared to those sampled at the feedlot (1.74%; 95% CI: 0.53-3.44%). Prevalence of E. coli O157 on carcass surfaces differed by season only at the post-evisceration stage, but decreased considerably through the subsequent processing stages. Country, study setting, detection method, hide swab area, and study design were identified as significant sources of heterogeneity among studies reporting prevalence of E. coli O157 along the beef production chain. The pooled prevalence and concentration estimates from this study provide a sound and reliable microbiological basis for risk assessment modeling of E. coli O157 and other pathogens in the food chain. PMID- 26153555 TI - Seventh Joint Meeting of K-J-CaP and CaPSURE: extending the global initiative to improve prostate cancer management. AB - This report summarizes the presentations and discussions that took place at the Seventh Joint Meeting of the Korea-Japan Study Group of Prostate Cancer (K-J-CaP) and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) held in Seoul, Korea, in September 2013. The original J-CaP and CaPSURE Joint Initiative has now been established since 2007 and since the initial collaboration between research teams in the United States (US) and Japan, the project has expanded to include several other Asian countries. The objective of the initiative is to analyze and compare data for prostate cancer patients in the participating countries, looking at similarities and differences in patient management and outcomes. Until now the focus has been primarily on data generated within J-CaP and CaPSURE, both large-scale, longitudinal, observational databases of prostate cancer patients in Japan and the US, respectively. This year's meeting was hosted for the first time in Korea which has recently established its own national database-K-CaP-to add to the wealth of data generated by J-CaP and CaPSURE. As a newly-developed database, K-CaP has also provided a valuable 'template' for other countries, such as China and Indonesia, planning to establish their own national databases and this will ultimately allow greater opportunities for international data comparisons. A range of topics was discussed at this Seventh Joint Meeting including comparison of outcomes following androgen deprivation therapy or radical prostatectomy in patients with localized prostate cancer, the use of active surveillance as a treatment option and the triggers for intervention when employing this regimen, patient quality of life during treatment, the impact of comorbidities on outcomes, and a comparison of recent outcomes data between J-CaP and CaPSURE. The participants recognized that prostate cancer was now a global disease and therefore major insights into understanding and improving the management of this condition would arise from global interactions such as this joint initiative. PMID- 26153556 TI - Modelling the dynamics of ambient dose rates induced by radiocaesium in the Fukushima terrestrial environment. AB - Since the Fukushima accident, Japanese scientists have been intensively monitoring ambient radiations in the highly contaminated territories situated within 80 km of the nuclear site. The surveys that were conducted through mainly carborne, airborne and in situ gamma-ray measurement devices, enabled to efficiently characterize the spatial distribution and temporal evolution of air dose rates induced by Caesium-134 and Caesium-137 in the terrestrial systems. These measurements revealed that radiation levels decreased at rates greater than expected from physical decay in 2011-2012 (up to a factor of 2), and dependent on the type of environment (i.e. urban, agricultural or forest). Unlike carborne measurements that may have been strongly influenced by the depuration of road surfaces, no obvious reason can be invoked for airborne measurements, especially above forests that are known to efficiently retain and recycle radiocaesium. The purpose of our research project is to develop a comprehensive understanding of the data acquired by Japanese, and identify the environmental mechanisms or factors that may explain such decays. The methodology relies on the use of a process-based and spatially-distributed dynamic model that predicts radiocaesium transfer and associated air dose rates inside/above a terrestrial environment (e.g., forests, croplands, meadows, bare soils and urban areas). Despite the lack of site-specific data, our numerical study predicts decrease rates that are globally consistent with both aerial and in situ observations. The simulation at a flying altitude of 200 m indicated that ambient radiation levels decreased over the first 12 months by about 45% over dense urban areas, 15% above evergreen coniferous forests and between 2 and 12% above agricultural lands, owing to environmental processes that are identified and discussed. In particular, we demonstrate that the decrease over evergreen coniferous regions might be due the combined effects of canopy depuration (through biological and physical mechanisms) and the shielding of gamma rays emitted from the forest floor by vegetation. Our study finally suggests that airborne surveys might have not reflected dose rates at ground level in forest systems, which were predicted to slightly increase by 5-10% during the same period of time. PMID- 26153557 TI - Postoperative support of the ala nasi with a modified nasal oxygen catheter. PMID- 26153558 TI - The role of imaging methods in the diagnosis of pulmonary lipoma. PMID- 26153559 TI - Trends in Lung Cancer Incidence in a Healthcare Area. AB - The aim of this study was to identify trends in the incidence of lung cancer in the Leon Healthcare Area. All cases of cancer among residents of the Leon healthcare catchment area listed in the hospital-based tumor registry of the Centro Asistencial Universitario de Leon (CAULE) between 1996 and 2010 were included. Gross incidence rates over 3-year intervals were calculated and adjusted for the worldwide and European populations. A total of 2,491 cases were included. In men, incidence adjusted for the European population rose from 40.1 new cases per 100,000 population (1996-1998) to 61.8 (2005-2007), and then fell to 54.6 (2008-2010). In women, incidence tripled from 3.0 (1996-1998) to 9.2 new cases per 100,000 (2008-2010). Although lung cancer is an avoidable disease, it is a serious problem in the Leon Healthcare Area. Of particular concern is the rising incidence among women. PMID- 26153560 TI - Pulmonary and Breast Tuberculosis: An Unusual Association. PMID- 26153561 TI - The role of imaging in suspected pulmonary artery tumors. PMID- 26153562 TI - Soft-Tissue Mass. An Unusual Presentation of Metastatic Squamous Cell Lung Carcinoma. PMID- 26153563 TI - Adolescent Urology and Transitional Care. AB - Babies with the major congenital anomalies of the genito-urinary tract have all embracing holistic care during childhood. They require the same level of care in adult life. This is the role of transition and adolescent urology. PMID- 26153564 TI - Metastatic Prostate Cancer and the Bone: Significance and Therapeutic Options. AB - CONTEXT: Skeletal involvement is common in metastatic prostate cancer (PCa) and is associated with skeletal-related events (SREs). The interaction of PCa with the bone microenvironment contributes to self-perpetuating progression of cancer in bone. Bone-targeted agents (BTAs) are available for use in metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To review the biology of bone metastases in PCa and to review the clinical trial data for BTAs in PCa. EVIDENCE ACQUISITION: A literature search was conducted in October 2014. Keywords included clinical trial, prostate cancer, denosumab, bisphosphonates, zoledronic acid, radium-223, bone turnover markers, skeletal-related events, and symptomatic skeletal events. EVIDENCE SYNTHESIS: The biology of bone metastases in PCa is summarized. Data supporting the use of BTAs in PCa are reviewed, and issues related to the combination and sequencing of available agents are discussed. CONCLUSIONS: The osteoclast-targeted agents zoledronic acid and denosumab decrease SREs in mCRPC, and the alpha-emitting radiopharmaceutical agent radium 223 improves survival and decreases symptomatic skeletal events. Limited data are available to guide the sequence and combination of BTAs with disease-modifying agents, although data support the use of osteoclast-targeted drugs with chemotherapy, androgen-targeted agents, and radium-223. Zoledronic acid does not reduce SREs when started prior to castration resistance, although osteoclast targeted agents do improve outcomes when used in patients with asymptomatic to minimally symptomatic chemotherapy-naive mCRPC. The optimal sequence of radium 223 with chemotherapy is uncertain, although data suggest the efficacy and tolerability of radium-223 is similar with either sequence. Clinical trials evaluating the combination of BTAs with other agents are under way. The optimization of sequence and combination strategies will guide the best use of available agents. PATIENT SUMMARY: The literature pertaining to bone metastases in prostate cancer (PCa) was reviewed, and the current understanding of the biology of PCa having spread to bone and the agents available to reduce skeletal complications was discussed. PMID- 26153565 TI - JAK2-positive cutaneous myelofibrosis presenting as sclerosing extramedullary hematopoietic tumors on the scalp: case presentation and review of the literature. AB - We report the second case of cutaneous myelofibrosis with a documented JAK2 activating mutation involving the scalp of a 67-year-old woman with primary myelofibrosis in her marrow. In contrast to the previous case, the biopsy revealed extensive lesional collagen deposition and closely mimicked a fibrohistiocytic proliferation. Similar rare lesions occurring in the setting of myeloproliferative neoplasms have been called sclerosing extramedullary hematopoietic tumors. These entities appear histomorphologically and etiologically distinct from extramedullary hematopoiesis, and their diagnosis should prompt the workup for a myeloproliferative neoplasm in the absence of an antecedent diagnosis. The presence of the JAK2 mutation in our case confirmed that the lesions represented skin involvement by a neoplastic myeloid proliferation and not compensatory extramedullary hematopoiesis. Our patient died of disease several months following the appearance of her lesions, which is in keeping with other reports that suggest that cutaneous myelofibrosis may serve as an independent poor prognostic sign in otherwise advanced primary myelofibrosis. A review of the literature further emphasizes the importance of distinguishing this entity from mesenchymal neoplasms and acute myeloid leukemia involving the skin. PMID- 26153566 TI - Nonlinear concentration gradients regulated by the width of channels for observation of half maximal inhibitory concentration (IC50) of transporter proteins. AB - This paper describes a simple microfluidic device that can generate nonlinear concentration gradients. We changed the "width" of channels that can drastically shorten the total microfluidic channel length and simplify the microfluidic network design rather than the "length" of channels. The logarithmic concentration gradients generated by the device were in good agreement with those obtained by simulation. Using this device, we evaluated a probable IC50 value of the ABC transporter proteins by the competitive transport assays at five different logarithmic concentrations. This probable IC50 value was in good agreement with an IC50 value (0.92 MUM) obtained at the diluted concentrations of seven points. PMID- 26153568 TI - A simple dual online ultra-high pressure liquid chromatography system (sDO-UHPLC) for high throughput proteome analysis. AB - We report a new and simple design of a fully automated dual-online ultra-high pressure liquid chromatography system. The system employs only two nano-volume switching valves (a two-position four port valve and a two-position ten port valve) that direct solvent flows from two binary nano-pumps for parallel operation of two analytical columns and two solid phase extraction (SPE) columns. Despite the simple design, the sDO-UHPLC offers many advantageous features that include high duty cycle, back flushing sample injection for fast and narrow zone sample injection, online desalting, high separation resolution and high intra/inter-column reproducibility. This system was applied to analyze proteome samples not only in high throughput deep proteome profiling experiments but also in high throughput MRM experiments. PMID- 26153567 TI - Lifetimes and stabilities of familiar explosive molecular adduct complexes during ion mobility measurements. AB - Trapped ion mobility spectrometry coupled to mass spectrometry (TIMS-MS) was utilized for the separation and identification of familiar explosives in complex mixtures. For the first time, molecular adduct complex lifetimes, relative stability, binding energies and candidate structures are reported for familiar explosives. Experimental and theoretical results showed that the adduct size and reactivity, complex binding energy and the explosive structure tailor the stability of the molecular adduct complex. The flexibility of TIMS to adapt the mobility separation as a function of the molecular adduct complex stability (i.e., short or long IMS experiments/low or high IMS resolution) permits targeted measurements of explosives in complex mixtures with high confidence levels. PMID- 26153569 TI - Self-assembly of various silver nanocrystals on PmPD/PAN nanofibers as a high performance 3D SERS substrate. AB - We report a facile method to synthesise flexible 3D surface-enhanced Raman scattering (SERS) substrates, using poly-m-phenylenediamine/polyacrylonitrile (PmPD/PAN) nanofiber mats as templates to self-assemble citrate-stabilized Ag nanocrystals (AgNCs), such as Ag nanoparticles (AgNPs), Ag nanotriangles (AgNTs) or Ag nanodisks (AgNDs). The SERS performances of AgNC@2D and AgNC@3D substrates were compared using 4-MBA as the probe molecule. The effect of the extinction wavelength as well as the density and morphology of the AgNCs on the SERS enhancement effect was explored. The results suggest that the 3D AgNT@PmPD/PAN nanofiber mat exhibits the highest SERS sensitivity and the lowest relative standard deviation (RSD) value. The detection limit of 4-MBA is as low as 10(-8) M, making the nanofiber mat a promising candidate for the SERS detection of chemical molecules. In addition, this study provides a simple route for the fabrication of SERS substrates with different types of noble metals and materials with strong SERS enhancement performance. PMID- 26153570 TI - The (13)C amide I band is still sensitive to conformation change when the regular amide I band cannot be distinguished at the typical position in H2O. AB - The attenuated total reflection technique was utilized to obtain FTIR spectra of (13)C-labeled peptides with a sequence of (AAAAK)4AAAAY in H2O. The regular amide I band was not at the typical position as reported in globular proteins, whereas the (13)C amide I band was still sensitive to conformation change. PMID- 26153571 TI - Simulating the inhibition reaction of Mycobacterium tuberculosis L,D transpeptidase 2 by carbapenems. AB - A theoretical free energy study describes the inactivation of a new tuberculosis target, the l,d-transpeptidase 2 enzyme. A new reaction mechanism of two carbapenem inhibitors is proposed and their molecular features are determined using QM/MM and PMF approaches. The theoretical findings with the new proposed mechanism agree in principle with the experimental data. PMID- 26153572 TI - Controlled release from protein particles encapsulated by molecular layer deposition. AB - Molecular layer deposition (MLD) was used to coat micron-sized protein particles in a fluidized bed reactor. Our results show that the dissolution rate of particles coated via MLD rapidly decreases with the increase in number of coating cycles, while the uncoated particles dissolve instantaneously. PMID- 26153573 TI - Receptor selective ruthenium-somatostatin photosensitizer for cancer targeted photodynamic applications. AB - The efficient conjugation of a ruthenium complex and the peptide hormone somatostatin is presented. The resultant biohybrid offers valuable features for photodynamic therapy such as remarkable cellular selectivity, rapid cell uptake by receptor-mediated endocytosis, efficient generation of (1)O2 upon irradiation, potent phototoxicity as well as low cytotoxicity in the "off"-state. PMID- 26153574 TI - Site-specific indolation of proline-based peptides via copper(II)-catalyzed oxidative coupling of tertiary amine N-oxides. AB - The first site-specific and purely chemical method for modifying proline-based peptides was developed via a convenient, copper-catalyzed oxidative coupling of tertiary amine N-oxides with indoles. This novel approach features high regioselectivity and diastereoselectivity, mild conditions, and compatibility with various functional groups. In addition, a simplified process was realized in one pot and two steps via in situ oxidative coupling of tertiary amine and indoles. PMID- 26153575 TI - A novel bipolar phosphorescent host for highly efficient deep-red OLEDs at a wide luminance range of 1000-10 000 cd m(-2). AB - A novel phosphorescent host FPYPCA possessing the bipolar charge transporting ability realizes the most efficient deep-red PhOLED, which maintains very high level EQEs of >23% at rather a high and wide luminance range of 1000-10 000 cd m( 2). PMID- 26153576 TI - [Implant sparing in prosthetic joint infection: Yes, if you use ciprofloxacin!]. PMID- 26153577 TI - [Does the antitoxin activity of clindamycin decrease mortality in invasive streptococcal infections?]. PMID- 26153578 TI - [Anti-HPV vaccine: More data supporting the vaccination of women more than 19 years of age and of men]. PMID- 26153579 TI - Vitamin D receptor (VDR) genetic polymorphisms associated with intervertebral disc degeneration. PMID- 26153580 TI - Improved accuracy of markerless motion tracking on bone suppression images: preliminary study for image-guided radiation therapy (IGRT). AB - The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images obtained by the dual-energy subtraction technique. This study was performed to evaluate the usefulness of bone suppression image processing in image-guided radiation therapy. We demonstrated the improved accuracy of markerless motion tracking on bone suppression images. Chest fluoroscopic images of nine patients with lung nodules during respiration were obtained using a flat-panel detector system (120 kV, 0.1 mAs/pulse, 5 fps). Commercial bone suppression image processing software was applied to the fluoroscopic images to create corresponding bone suppression images. Regions of interest were manually located on lung nodules and automatic target tracking was conducted based on the template matching technique. To evaluate the accuracy of target tracking, the maximum tracking error in the resulting images was compared with that of conventional fluoroscopic images. The tracking errors were decreased by half in eight of nine cases. The average maximum tracking errors in bone suppression and conventional fluoroscopic images were 1.3 +/- 1.0 and 3.3 +/- 3.3 mm, respectively. The bone suppression technique was especially effective in the lower lung area where pulmonary vessels, bronchi, and ribs showed complex movements. The bone suppression technique improved tracking accuracy without special equipment and implantation of fiducial markers, and with only additional small dose to the patient. Bone suppression fluoroscopy is a potential measure for respiratory displacement of the target. PMID- 26153581 TI - In memoriam: Paul J. Bedard, MD PhD: January 19, 1942-December 26, 2014?. PMID- 26153582 TI - Women in metabolism: part I. AB - In continuing our 10th anniversary celebrations, we asked women scientists in the metabolism field to share their stories and words of wisdom for the new generation and are happy to present the first 12 Voices of our "Women in Metabolism" series. PMID- 26153583 TI - CLINICAL PATHOLOGIC CONFERENCE CASE 1: A MULTILOCULAR RADIOLUCENCY IN THE POSTERIOR MANDIBLE. PMID- 26153584 TI - CLINICAL PATHOLOGIC CONFERENCE CASE 2: PALATAL PERFORATION. PMID- 26153585 TI - CLINICAL PATHOLOGIC CONFERENCE CASE 3: A 15-YEAR-OLD MALE WITH A RADIOLUCENT JAW LESION. PMID- 26153586 TI - CLINICAL PATHOLOGIC CONFERENCE CASE 4: A YELLOWISH SPECKLED PLAQUE OF BUCCAL MUCOSA. PMID- 26153587 TI - CLINICAL PATHOLOGIC CONFERENCE CASE 5: A MALE NAVY DIVER WITH ORAL AND SKIN LESIONS. PMID- 26153588 TI - CLINICAL PATHOLOGIC CONFERENCE CASE 6: PROLIFERATIVE MAXILLARY MASS. PMID- 26153589 TI - [Development of a questionnaire to identify patients' preference for a conventional or a direct oral anticoagulant]. AB - BACKGROUND: Oral anticoagulant therapy is currently performed using vitamin K dependent (VKA) or novel, non-vitamin-K-dependent (NOAC) anticoagulants. Patients can thus be involved into the decision process which type of anticoagulants to use. Preference of patients for a specific type of anticoagulants is included in several international guidelines for prophylaxis of embolic events in patients with atrial fibrillation. METHOD: Description of the development of a short questionnaire to identify this preference in patients treated with VKA. RESULTS: Using the questionnaires Freiburger personality inventory (FPI-R), health survey SF-12, State-Trait Anxiety Inventory (STAI) and a self-developed questionnaire on anticoagulant therapy, multiple regression analysis identified 7 items for the willingness of patients to change anticoagulation from VKA to NOAC with a probability of about 90%. CONCLUSION: Further investigations have to be performed to identify the preference of patients for anticoagulation with VKA using this short questionnaire. PMID- 26153590 TI - [After the crisis is before the crisis: Coping-strategies for public health emergency situations on different levels--experiences of the German E. coli outbreak 2011]. AB - The German E. coli crisis in 2011 posed multifaceted challenges to the actors of the German health care system. This paper analyzes the outbreak from a multidisciplinary perspective. It offers best practices and general recommendations for future public health emergencies for hospitals as well as at the federal and local level, addressing medical practitioners as well as health care managers. PMID- 26153591 TI - [Effect of silymarin on liver health and quality of life. Results of a non interventional study]. AB - BACKGROUND: Many drugs are known to have hepatotoxic side effects. The effect of silymarin on liver function and liver-injury-impaired quality of life under daily practice conditions in patients with elevated values of liver enzymes was evaluated in the present non-interventional study. METHOD: Patients with drug induced elevated aminotransferase levels and indication for silymarin (Legalon forte) treatment for 2 to 3 months were documented prospectively over 4 months. At baseline, after 2 and 4 months, respectively, the following parameters were documented: alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyltransferase (GGT), alkaline phosphatase, total bilirubin, presence of liver-related skin symptoms and discoloured urine, severity of liver-related symptoms and quality of life. RESULTS: In total, 190 patients (53.2% male, median age 60.0 years [range 19-81]) from 48 centres participated in the non interventional study. Among potentially hepatotoxic drugs, analgesics/anti inflammatory drugs were used most frequently (45.8%). These drugs have been administered for a median period of 2.8 years (range 0.0-26.1). At baseline, all patients had elevated levels of ALT, AST or GGT. Fatigue, flatulence, upper abdominal discomfort, lethargy, and joint complaints were the most severe liver related symptoms and prevalent in over 62% of patients. Quality of life was affected in 88.7% of patients. Significant reductions were achieved in all documented laboratory parameters (p < 0.001), leading to marked improvement in liver-related symptoms and increased quality of life already after 2 months. The percentage of patients with liver enzymes in the normal range increased considerably within 4 months. No adverse drug reactions were observed. CONCLUSIONS: Silymarin is a safe and efficacious treatment option for patients with elevated liver enzymes. A benefit in terms of liver-related symptoms as well as quality of life and performance was demonstrated already after 2 months of treatment. PMID- 26153592 TI - [Long-term-treatment of chronic pain patients with flupirtine--on hepatotoxicity and persistent effectiveness from 7 months to 22 years]. AB - BACKGROUND: After an extended series of investigations in animals, healthy volunteers and pain patients with different methods, flupirtine was introduced in 1986 into the German market. Flupirtine has a unique chemical structure and differs in its profile of effects and side effects from established NSAIDs (non steroidal anti-inflammatory drugs) on the one hand and from opioids on the other hand. In the years after introduction, muscle relaxing effects were observed and experimentally shown. They were therapeutically utilized in tension-associated pain. Evidence of the efficacy in acute and chronic musculoskeletal pain syndromes was verified in many controlled and in open studies. METHOD: Experience report and case presentation RESULTS: The report in this paper of long-term treatment of chronic pain patients from 7 months to 22 years principally confirms its persistent effectiveness and tolerability. Tiredness and dizziness are frequent side effects. Flupirtine-associated hepatotoxicities are rare events. CONCLUSION: For pain patients for which NSAIDs or opioids are contraindicated or in appropriate, flupirtine is a necessary option. PMID- 26153612 TI - Fibrosing Bronchiolitis Evolving from Infectious or Inhalational Acute Bronchiolitis. A Reversible Lesion. AB - RATIONALE: Occasional cases of bronchiolitis show pathologic features somewhat suggestive of constrictive bronchiolitis, but with granulation tissue plugs that variably occlude the lumen in a pattern more typical of organizing pneumonia. These cases are poorly defined in the literature and the course of patients with this pattern of disease is unclear. OBJECTIVE: To describe an uncommon and potentially treatable pattern of acute bronchiolitis that has been termed fibrosing bronchiolitis. MAIN RESULTS: We report three patients with respiratory failure and acute onset of probable infectious or inhalational bronchiolitis that was characterized by centrilobular nodules and a variable tree-in-bud appearance on computed tomography. All patients showed an uncommon pattern of bronchiolitis on surgical lung biopsy. The pathologic abnormalities were confined to the bronchioles and consisted of reepithelialized, partially collagenized and variably polypoid plugs of granulation tissue that narrowed the bronchiolar lumens. All three patients improved dramatically on immunosuppressive therapy. CONCLUSIONS: These cases of fibrosing bronchiolitis represent an uncommon pattern of acute bronchiolitis that is reversible if detected at an early stage. Early recognition and treatment may prevent development of permanent bronchiolar fibrosis. PMID- 26153613 TI - Recurrent respiratory papillomatosis progressing into squamous cell carcinoma in an HIV-positive patient. PMID- 26153615 TI - Fluorinated Pickering Emulsions with Nonadsorbing Interfaces for Droplet-based Enzymatic Assays. AB - This work describes the use of fluorinated Pickering emulsions with nonadsorbing interfaces in droplet-based enzymatic assays. State-of-the-art droplet assays have relied on one type of surfactants consisting of perfluorinated polyether and polyethylene glycol (PFPE-PEG). These surfactants are known to have limitations including the tedious synthesis and interdrop molecular transport which leads to the cross-contamination of droplet contents. Previously we have shown that replacing surfactants with nanoparticles as droplet stabilizers mitigate interdrop transport of small molecules. The nonspecific adsorption of enzymes on nanoparticle surface, however, could cause structural changes in enzymes and consequently the loss of enzymatic activity. To overcome such challenge, we render nanoparticle surface nonadsorbing to enzymes by in situ adsorption of polyethylene glycol (PEG) on particle surfaces. We show that enzyme activities are preserved in droplets stabilized by PEG-adsorbed nanoparticles, and are comparable with those in drops stabilized by PFPE-PEG surfactants. In addition, our nonadsorbing Pickering emulsions successfully prevent interdrop molecular transport, thereby maintaining the accuracy of droplet assays. The particles are also simple and economical to synthesize. The PEG-adsorbed nanoparticles described in this work are thus a competitive alternative to the current surfactant system, and can potentially enable new droplet-based biochemical assays. PMID- 26153614 TI - A High-Efficiency Cellular Extraction System for Biological Proteomics. AB - Recent developments in quantitative high-resolution mass spectrometry have led to significant improvements in the sensitivity and specificity of the biochemical analyses of cellular reactions, protein-protein interactions, and small-molecule drug discovery. These approaches depend on cellular proteome extraction that preserves native protein activities. Here, we systematically analyzed mechanical methods of cell lysis and physical protein extraction to identify those that maximize the extraction of cellular proteins while minimizing their denaturation. Cells were mechanically disrupted using Potter-Elvehjem homogenization, probe- or adaptive-focused acoustic sonication, and were in the presence of various detergents, including polyoxyethylene ethers and esters, glycosides, and zwitterions. Using fluorescence spectroscopy, biochemical assays, and mass spectrometry proteomics, we identified the combination of adaptive focused acoustic (AFA) sonication in the presence of a binary poloxamer-based mixture of octyl-beta-glucoside and Pluronic F-127 to maximize the depth and yield of the proteome extraction while maintaining native protein activity. This binary poloxamer extraction system allowed for native proteome extraction comparable in coverage to the proteomes extracted using denaturing SDS or guanidine-containing buffers, including the efficient extraction of all major cellular organelles. This high-efficiency cellular extraction system should prove useful for a variety of cell biochemical studies, including structural and functional proteomics. PMID- 26153616 TI - Discovery of Novel CXCR2 Inhibitors Using Ligand-Based Pharmacophore Models. AB - The chemokine receptor CXCR2 is expressed on various immune cells and is essential for neutrophil recruitment and angiogenesis at sites of acute and chronic inflammation caused by tissue injury or infection. CXCR2 and its ligand, CXCL8, are implicated in a number of inflammation-mediated diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and cancer. Though the development of CXCR2-specific small-molecule inhibitors as anti-inflammatory agents has been pursued by pharmaceutical companies within the past decade, there are currently no clinically approved CXCR2 inhibitors. A pharmacophore model based on previously reported CXCR2 antagonists was developed to screen a database of commercially available compounds. Small-molecule compounds identified from the pharmacophore screening were selected for in vitro screening in a cell-based CXCR2-mediated beta-arrestin-2 recruitment assay and further characterized in several cell-based assays and lipopolysaccharide (LPS)-induced lung inflammation studies in mice. CX compounds identified from pharmacophore modeling inhibited cell migration, lung and colon cancer cell proliferation, and colony formation. Mechanistic studies of CX4152 showed that this compound inhibits CXCR2 signaling through downregulation of surface CXCR2. Additionally, CX4152 significantly inhibits CXCL8-mediated neutrophil migration and LPS-induced lung inflammation in mice. Using a CXCR2-inhibitor-based pharmacophore model, we identified a novel set of sulfonamides from a diverse library of small molecules. These compounds inhibit CXCR2/beta-arrestin-2 association, cell migration and proliferation, and acute inflammation in mouse models. CX compounds identified from our pharmacophore models are potential leads for further optimization and development as anti-inflammatory and anticancer agents. PMID- 26153617 TI - Rapid Reverse Genetic Screening Using CRISPR in Zebrafish. PMID- 26153618 TI - Controlling the Morphology of Organic Crystals with Filamentous Bacteriophages. AB - The preparation of thiamethoxam (TMX) organic crystals with high morphological uniformity was achieved by controlled aggregation-driven crystallization of primitive TMX crystals and phage using the filamentous M13 bacteriophage. The development of a regular, micrometer-sized, tetragonal-bipyramidal crystal structure was dependent on the amount of phage present. The phage appears to affect the supersaturation driving force for crystallization. The phage adsorption isotherm to TMX was well-fitted by the Satake-Yang model, which suggests a cooperative binding between neighboring phages as well as a binding of phage with the TMX crystal surface. This study shows the potential of phage additives to control the morphology and morphological uniformity of organic crystals. PMID- 26153619 TI - New Class of Heterogeneous Helical Peptidomimetics. AB - A new class of unnatural heterogeneous foldamers is reported to contain alternative alpha-amino acid and sulfono-gamma-AA amino acid residues in a 1:1 repeat pattern. Two-dimensional NMR data show that two 1:1 alpha/sulfono-gamma-AA peptides with diverse side chains form analogous right-handed helical structures in solution. The effects of sequence length, side chain, N-capping, and temperature on folding propensity were further investigated using circular dichroism and small-angle X-ray scattering. PMID- 26153620 TI - Surface Nanobubbles in Nonaqueous Media: Looking for Nanobubbles in DMSO, Formamide, Propylene Carbonate, Ethylammonium Nitrate, and Propylammonium Nitrate. AB - Surface nanobubbles produced by supersaturation during the exchange of ethanol for water are routinely observed on hydrophobic surfaces, are stable for days, and have contact angles that are very much greater than observed macroscopically. Here, we test the hypothesis that nanobubbles can also be observed in nonaqueous solvents in order to ascertain if their anomalous lifetimes and contact angles are related to properties of the solvent. Nanobubbles were seen in the protic solvents formamide, ethylammonium nitrate, and propylammonium nitrate, but not in propylene carbonate or dimethyl sulfoxide. Solvents in which nanobubbles were observed exhibit a three-dimensional hydrogen-bonding network. Like in aqueous systems, the nanobubbles were stable for days and exhibited high contact angles (~165 degrees ). PMID- 26153622 TI - Structures to the people! AB - A combination of 3D modeling and high-throughput sequencing may offer a faster way to determine the three-dimensional structures of RNA molecules. PMID- 26153621 TI - Anatomy of BioJS, an open source community for the life sciences. AB - BioJS is an open source software project that develops visualization tools for different types of biological data. Here we report on the factors that influenced the growth of the BioJS user and developer community, and outline our strategy for building on this growth. The lessons we have learned on BioJS may also be relevant to other open source software projects. PMID- 26153623 TI - Laryngeal adenoid cystic carcinoma: A population-based perspective. AB - OBJECTIVES/HYPOTHESIS: Adenoid cystic carcinoma (ACC) occurs infrequently in the larynx. Consequently, no large samples describing its clinical behavior are available in the literature. Our objective was to use a nationally representative population-based resource to evaluate clinical behavior, patient demographics, and outcomes among patients diagnosed with laryngeal ACC (LACC). STUDY DESIGN: Retrospective database analysis. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was analyzed for patients diagnosed with LACC between 1973 and 2011. Patient demographics, incidence, treatment, and survival between LACC and other laryngeal malignancies were compared. RESULTS: Of 69 LACC patients, 63.8% were female, 78.2% Caucasian, and the median age was 54 years. LACC patients were much more likely to have subglottic lesions (44.9%) than individuals with other malignancies (1.6%). The incidence of LACC was 0.005/100,000 individuals. The majority of patients with LACC harbored T4 lesions at initial diagnosis, although 87.9% had N0 disease, and only 6.1% had distant metastasis at diagnosis. Disease-specific survival (DSS) was greater at 1 year for LACC compared to other laryngeal malignancies, but not at 5 or 10 years. Five-year DSS was greater for LACC patients who underwent surgery versus those who did not undergo surgery. CONCLUSIONS: This analysis notes that LACC has a low incidence with no significant change in incidence over the study period. Compared to other laryngeal malignancies, LACC has a female preponderance, is much more common in the subglottis, presents at a younger age, and more often presents with T4 disease. Surgery was noted to confer a survival advantage in LACC. LEVEL OF EVIDENCE: 4. PMID- 26153624 TI - Correlates of Condom Use Among Somali and Ethiopian Immigrants in the U.S. AB - The study examined correlates of consistent condom use in steady heterosexual relationships among Somali and Ethiopian immigrants in Minnesota. Study participants (n = 205) responded to questions on attitudes, social norms, perceived behavioral control, self-efficacy, behavioral intention, and self reported male condom use. Participants were neither for, nor against using condoms, and the same was true for social influence and self-efficacy; however, reported moderately favorable attitude toward condom use and little difficulties in using condoms. Self-efficacy emerged as the factor with the strongest direct influence on behavioral intention to use condoms. In turn, behavioral intention was a significant predictor of self-reported condom use. Increasing male condom use self-efficacy among Somali and Ethiopian immigrants is suggested as a main component of public health intervention seeking to curb the spread of HIV and other STIs in Minnesota. PMID- 26153625 TI - Cyclic AMP Mimics the Anti-ageing Effects of Calorie Restriction by Up-Regulating Sirtuin. AB - Cyclic adenosine monophosphate (cAMP) plays an important role in many biological processes as a second messenger, and cAMP treatment has been reported to extend the lifespan of wild-type Drosophila melanogaster. Our study showed that exogenous cAMP improved ageing-related phenotypes by increasing the protein level of Sirtuins, which prevented metabolic disorders to mimic the effect of calorie restriction. Experiments in vitro showed that cAMP directly bound to SIRT1 and SIRT3 and consequently increased their activity. These findings suggest that cAMP slows the ageing process and is a good candidate to mimic calorie restriction. Our research provides a promising therapeutic strategy to target metabolic disorder-induced ageing-related diseases. PMID- 26153627 TI - Endoglin in HIV-associated preeclamptic placentae. AB - OBJECTIVE: To examine the placental immunoexpression of endoglin (Eng), in HIV negative and HIV-positive normotensive (N- and N+) and preeclamptic (P- and P+) pregnancies at term, using immunohistochemistry and immunoelectron microscopy. RESULTS: Strong Eng immunoreactivity was observed within endothelial cells, syncytio- and cyto-trophoblast cell populations. All extravillous trophoblast cells were immunopositive for Eng. Subcellularly, gold particles were immunolocalised within the endoplasmic reticulum, and mitochondria. Immunoexpression of Eng differed significantly between exchange (p = 0.02) and conducting villi (p < 0.001). A higher Eng immunoexpression was observed in both villi types of the preeclamptic compared to normotensive groups. Irrespective of pregnancy type (normotensive versus PE), there was no significant effect of HIV status on Eng immunoexpression within the exchange and conducting villi. CONCLUSION: The immunostaining of Eng within the endothelial cells, syncytio-, cyto- and extravillous trophoblast cell populations of HIV-associated preeclamptic placentae is novel. Endoglin and its soluble component remains an area for dynamic placental exploration in preeclampsia development. PMID- 26153626 TI - Association between wood cooking fuel and maternal hypertension at delivery in central East India. AB - OBJECTIVE: Smoke from burning of biomass fuels has been linked with adverse pregnancy outcomes and hypertension among nonpregnant subjects; association with hypertension during pregnancy has not been well studied. We evaluated whether the use of wood cooking fuel increases the risk of maternal hypertension at delivery compared to gas which burns with less smoke. METHODS: Information on fuel use and blood pressure was available for analysis from a cross-sectional survey of 1369 pregnant women recruited at delivery in India. RESULTS: Compared to gas users, women using wood as fuel had on average lower mean arterial pressure (adjusted effect size - 2.0 mmHg; 95% CI: -3.77, -0.31) and diastolic blood pressure (adjusted effect size -1.96 mmHg; 95% CI: -3.60, -0.30) at delivery. Risk of hypertension (systolic >139 mmHg or diastolic >89 mmHg) was 14.6% for wood users compared to 19.6% for gas users although this did not reach significance after adjustment, using propensity score techniques, for factors that make wood and gas users distinct (adjusted prevalence ratio 0.76; 95% CI: 0.49, 1.17). CONCLUSIONS: Combustion products from the burning of biomass fuels are similar to those released with tobacco smoking, which has been linked with a reduced risk for preeclampsia. The direction of our findings suggests the possibility of a similar effect for biomass cook smoke. Whether clean cooking interventions being promoted by international advocacy organizations will impact hypertension in pregnancy warrants further analysis as hypertension remains a leading cause of maternal death worldwide and cooking with biomass fuels is widespread. PMID- 26153628 TI - Readability, content, and quality of online patient education materials on preeclampsia. AB - OBJECTIVE: The objective of this study was to evaluate the readability, content, and quality of patient education materials addressing preeclampsia. METHODS: Websites of U.S. obstetrics and gynecology residency programs were searched for patient education materials. Readability, content, and quality were assessed. A one-sample t-test was used to evaluate mean readability level compared with the recommended 6th grade reading level. RESULTS: Mean readability levels were higher using all indices (p < 0.001). Content was variable with good website understandability, but poor actionability. CONCLUSIONS: The mean readability was above the recommended 6th grade reading level. The content, readability, and actionability of preeclampsia patient education materials should be improved. PMID- 26153629 TI - Linking the old and new -- do angiotensin II type 1 receptor antibodies provide the missing link in the pathophysiology of preeclampsia? AB - Preeclampsia remains a leading cause of maternal and neonatal morbidity and mortality. The pathophysiology of preeclampsia remains poorly understood with various pathological mechanisms being implicated including the renin angiotensin system (RAAS), angiogenic pathways and various components of the immune system. Recently a pathogenic autoimmune factor has been identified in the form of auto agonistic angiotensin II type 1 receptor antibodies (AT1-AA). AT1-AA have been studied in vitro and in vivo in various human and animal models and these data have provided compelling evidence for their role in preeclampsia. This review summarises the current literature surrounding the role of AT1-AA in preeclampsia and draws links between this relatively novel antibody to well-established pathological mechanisms including the immune system, the RAAS, angiogenic pathways and placental ischaemia. PMID- 26153630 TI - Possible Biosphere-Lithosphere Interactions Preserved in Igneous Zircon and Implications for Hadean Earth. AB - Granitoids are silicic rocks that make up the majority of the continental crust, but different models arise for the origins of these rocks. One classification scheme defines different granitoid types on the basis of materials involved in the melting/crystallization process. In this end-member case, granitoids may be derived from melting of a preexisting igneous rock, while other granitoids, by contrast, are formed or influenced by melting of buried sedimentary material. In the latter case, assimilated sedimentary material altered by chemical processes occurring at the near surface of Earth-including biological activity-could influence magma chemical properties. Here, we apply a redox-sensitive calibration based on the incorporation of Ce into zircon crystals found in these two rock types, termed sedimentary-type (S-type) and igneous-type (I-type) granitoids. The ~400 Ma Lachlan Fold Belt rocks of southeastern Australia were chosen for investigation here; these rocks have been a key target used to describe and explore granitoid genesis for close to 50 years. We observe that zircons found in S-type granitoids formed under more reducing conditions than those formed from I type granitoids from the same terrain. This observation, while reflecting 9 granitoids and 289 analyses of zircons from a region where over 400 different plutons have been identified, is consistent with the incorporation of (reduced) organic matter in the former and highlights one possible manner in which life may modify the composition of igneous minerals. The chemical properties of rocks or igneous minerals may extend the search for ancient biological activity to the earliest period of known igneous activity, which dates back to ~4.4 billion years ago. If organic matter was incorporated into Hadean sediments that were buried and melted, then these biological remnants could imprint a chemical signature within the subsequent melt and the resulting crystal assemblage, including zircon. PMID- 26153633 TI - Scrofula and the Divine Right of Royalty: The King's Touch. PMID- 26153634 TI - On Leopards, Cheetahs, and the Cutaneous Stigmata of Onchocerciasis. PMID- 26153635 TI - Dermatologic Etymology: Configuration and Form. PMID- 26153636 TI - Incorrect Data in Figure. PMID- 26153637 TI - Radium: Curie's Perpetual Sunshine. PMID- 26153638 TI - Current and future strategies in nonclear-cell metastatic renal cell carcinoma. AB - PURPOSE OF REVIEW: Therapeutic options for patients with metastatic nonclear-cell renal cell carcinoma (non-ccRCC) are limited and display minimum benefit. Conducting clinical trials in these rare and heterogeneous diseases without identified key biological drivers is a challenge for drug development. A growing body of prospective dedicated clinical trials and large molecular characterization initiatives are raising new expectations in non-ccRCC. RECENT FINDINGS: The first randomized phase II study in non-ccRCC failed to demonstrate the benefit of everolimus over sunitinib in first-line setting, although this study was small and was not supposed to draw final conclusions. Single-arm phase II trials have reported the results of sunitinib or everolimus in the papillary. The potential role of a sunitinib-gemcitabine combination has been investigated in RCC with sarcomatoid features. In parallel, the molecular characterization of non-ccRCC has been initiated, highlighting the heterogeneity of the distinct subtypes. SUMMARY: Current efforts to develop clinical trials in non-ccRCC have provided preliminary results with approved agents. The molecular characterization programs have not yet translated into clinical meaningful results, but MET proto oncogene inhibition holds promises in the population of papillary RCC. Non-ccRCC management raises the challenge of structuring networks to optimize pathological diagnosis, target identification, and for dedicated clinical trials design. PMID- 26153639 TI - A precision, personalized approach to the management of bladder cancer. PMID- 26153640 TI - In situ growth of hierarchical NiS2 hollow microspheres as efficient counter electrode for dye-sensitized solar cell. AB - Hierarchical NiS2 hollow microspheres (HM-NiS2) were successfully in situ grown on FTO by a one-step hydrothermal method, and then tested as the counter electrode (CE) for dye-sensitized solar cell (DSSC) for the first time. The SEM images reveal that the hierarchical NiS2 microspheres were successfully grown on FTO substrate. It is worth noting that some of the shells are partially broken, which is advantageous for providing more electrolyte adsorptions and electrocatalytic active sites. The electrocatalytic ability and electrochemical properties of the HM-NiS2 were studied by cyclic voltammetry, electrochemical impedance spectroscopy and Tafel polarization. The power conversion efficiency of 7.84% is achieved for the DSSC based on HM-NiS2 CE, which is close to that of the DSSC using Pt CE (7.89%). The results indicate that the in situ fabricated HM NiS2 CE may be a good candidate for high efficiency and low-cost DSSCs. PMID- 26153641 TI - Structure and Stability of Pentafluoroaniline and 4-Aminononafluorobiphenyl Radical Anions: Optically Detected Electron Paramagnetic Resonance, Time-Resolved Fluorescence, Time-Resolved Magnetic Field Effect, and Quantum Chemical Study. AB - Radical anions (RAs) are the key intermediates of the selective hydrodefluorination of polyfluoroarenes. We used the techniques of optically detected electron paramagnetic resonance (OD EPR), time-resolved fluorescence, time-resolved magnetic field effect (TR MFE), and the density functional theory to study the possibility of RAs formation from 4-aminononafluorobiphenyl (1) and pentafluoroaniline (2) and estimate their lifetimes and decay channels. To our knowledge, both RAs have not been detected earlier. We have registered the OD EPR spectrum for relatively stable in nonpolar solutions 1(-*) but failed to register the spectra for 2(-*). However, we have managed to fix the 2(-*) by the TR MFE method and obtained its hyperfine coupling constants. The lifetime of 2(-*) was found to be only a few nanoseconds. The activation energy of its decay was estimated to be 3.6 +/- 0.3 kcal/mol. According to the calculation results, the short lifetime of 2(-*) is due to the RA fast fragmentation with the F(-) elimination from ortho-position to the amine group. The calculated energy barrier, 3.2 kcal/mol, is close to the experimental value. The fragmentation of 2(-*) in a nonpolar solvent is possible due to the stabilization of the incipient F(-) anion by the binding with the amine group proton. PMID- 26153642 TI - The indirect costs of systemic autoimmune diseases, systemic lupus erythematosus, systemic sclerosis and sarcoidosis: a summary of 2012 real-life data from the Social Insurance Institution in Poland. AB - Systemic lupus erythematosus, systemic sclerosis and sarcoidosis are three different autoimmune systemic diseases that generate a significant burden to society due to treatment costs and also those caused by a work disability or absenteeism among patients. Relevant 2012 data referring to the three components of absenteeism produced by autoimmune systemic diseases, sick leave, short-term and long-term work disability, were obtained from the Social Insurance Institution in Poland (PSII). By applying the Human Capital Approach using gross domestic product per capita, gross value added per worker and gross income per worker in 2012, total indirect costs for the diseases were calculated. All costs were presented in euros and were valid for 2012. The PSII recorded 1600 patients with systemic lupus erythematosus, 500 patients with systemic sclerosis and 2700 patients with sarcoidosis in the 2012 - total indirect costs were as high as 7,260,595, 2,268,571 and 4,027,575 EUR, respectively. Costs were estimated using gross domestic product per capita; 17,485,412, 5,463,312 and 9,699,455 EUR, accordingly, calculated using gross value added per worker and 5,346,933, 1,670,648 and 2,966,034 EUR estimated using gross income per worker, respectively. Considering only data on absenteeism gathered by the PSII we can conclude that the three autoimmune systemic diseases bore great indirect costs. Their social burden for Poland could be even greater when considering presenteeism as well as other components of absenteeism such as loss of unpaid work, a gray economy or loss of leisure time. PMID- 26153643 TI - A medical cost estimation with fuzzy neural network of acute hepatitis patients in emergency room. AB - Taiwan is an area where chronic hepatitis is endemic. Liver cancer is so common that it has been ranked first among cancer mortality rates since the early 1980s in Taiwan. Besides, liver cirrhosis and chronic liver diseases are the sixth or seventh in the causes of death. Therefore, as shown by the active research on hepatitis, it is not only a health threat, but also a huge medical cost for the government. The estimated total number of hepatitis B carriers in the general population aged more than 20 years old is 3,067,307. Thus, a case record review was conducted from all patients with diagnosis of acute hepatitis admitted to the Emergency Department (ED) of a well-known teaching-oriented hospital in Taipei. The cost of medical resource utilization is defined as the total medical fee. In this study, a fuzzy neural network is employed to develop the cost forecasting model. A total of 110 patients met the inclusion criteria. The computational results indicate that the FNN model can provide more accurate forecasts than the support vector regression (SVR) or artificial neural network (ANN). In addition, unlike SVR and ANN, FNN can also provide fuzzy IF-THEN rules for interpretation. PMID- 26153644 TI - Erratum: nuclear EGFRvIII-STAT5b complex contributes to glioblastoma cell survival by direct activation of the Bcl-XL promoter. PMID- 26153645 TI - Erratum: RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of aurora-a and BRCA2. PMID- 26153646 TI - Erratum-ovarian cancer cells, not normal cells, are damaged by mirk/dyrk1b kinase inhibition. PMID- 26153647 TI - Erratum: salt tea consumption and esophageal cancer: a possible role of alkaline beverages in esophageal carcinogenesis. PMID- 26153648 TI - Erratum: inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (sp) transcription factors. PMID- 26153650 TI - Photophysical and structural investigation of a (Py)A-modified adenine cluster: its potential use for fluorescent DNA probes exhibiting distinct emission color changes. AB - In this study, we found a (Py)A-modified adenine cluster (A-cluster), a minimum fluorescent unit for significant emission wavelength changes, and investigated its photophysical and structural properties. The basic A-cluster unit was an adenine-pentad duplex containing stacked (Py)A pairs in the center aligned in an antiparallel manner. Spectral analysis of the A-cluster revealed remarkable reddish fluorescence with a large Stokes shift (~195 nm) and a long life-time constant (31 ns), originated from exciton states formed by (Py)A pairs and neighboring adenines. Structurally, the exciton state of the A-cluster exhibited unusually high stability, relative to that of other five-mismatched duplexes, as a result of stabilization through strong stacking interactions (zipper-like structure) of the mismatched A-A and (Py)A pairs, rather than through traditional Watson-Crick base pairing. These spectral and structural properties of the A clusters were specific to the adenine bases and highly disturbed by introducing other bases (T, G, and especially C) or an abasic site into the A-cluster, whereas they were enhanced through synergistic effects in systems containing multiple A-clusters. As a minimum unit for these unique properties, finally, the A-cluster was exploited as a fluorescent probing system for specific nucleic acid sequences, such as miR-21, accompanying distinct fluorescence color changes from blue to red. These findings indicated the potential utility of the A-cluster as a part of fluorescent probes exhibiting clear signaling upon micro-environmental changes. PMID- 26153649 TI - Platelet-derived growth factor (PDGF) signalling in cancer: rapidly emerging signalling landscape. AB - Platelet-derived growth factor (PDGF)-mediated signalling has emerged as one of the most extensively and deeply studied biological mechanism reported to be involved in regulation of growth and survival of different cell types. However, overwhelmingly increasing scientific evidence is also emphasizing on dysregulation of spatio-temporally controlled PDGF-induced signalling as a basis for cancer development. We partition this multi-component review into recently developing understanding of dysregulation PDGF signalling in different cancers, how PDGF receptors are quantitatively controlled by microRNAs. Moreover, we also summarize most recent advancements in therapeutic targeting of PDGFR as evidenced by preclinical studies. Better understanding of the PDGF-induced intracellular signalling in different cancers will be helpful in catalysing the transition from a segmented view of cancer biology to a conceptual continuum. PMID- 26153651 TI - Synthesis of Pyrazolo[5,1-a]isoindoles and Pyrazolo[5,1-a]isoindole-3 carboxamides through One-Pot Cascade Reactions of 1-(2-Bromophenyl)buta-2,3-dien 1-ones with Isocyanide and Hydrazine or Acetohydrazide. AB - A novel and efficient method for the construction of the pyrazolo[5,1-a]isoindole scaffold via a one-pot three-component cascade reaction of 1-(2-bromophenyl)buta 2,3-dien-1-one with hydrazine and isocyanide promoted by a Pd catalyst is described. This cascade process proceeds through initial condensation of the allenic ketone with hydrazine followed by Pd-catalyzed isocyanide insertion into the C-Br bond and intramolecular C-N bond formation. Interestingly, when acetohydrazide was used in place of hydrazine, a more sophisticated procedure involving condensation, isocyanide insertion into C-H and C-Br bonds, deacetylation, and formation of C-C, C-O, and C-N bonds occurred to afford pyrazolo[5,1-a]isoindole-3-carboxamides with good efficiency. PMID- 26153652 TI - A simple and visible colorimetric method through Zr(4+)-phosphate coordination for the assay of protein tyrosine phosphatase 1B and screening of its inhibitors. AB - Inhibitors of protein tyrosine phosphatase 1B (PTP1B) are promising agents for the treatment of type 2 diabetes and obesity, so a colorimetric method has been developed in this work for PTP1B assay and screening of its inhibitors. The method is based on the chelation effect of zirconium (Zr(4+)) ions on the phosphate group, which may induce aggregation of 4-aminophenylphosphate functionalized gold nanoparticles (APP/AuNPs) and the corresponding color change of the testing solution. Owing to the dephosphorylation of PTP1B, the aggregation of AuNPs will be influenced by PTP1B since there is no coordination reactivity between Zr(4+) ions and 4-aminophenol, the hydrolyzed product of APP catalyzed by the enzyme. Therefore, a simple colorimetric method for the assay of PTP1B activity can be developed. Under the optimized experimental conditions, the ratios of absorbance at a wavelength of 650 nm to that at 522 nm vary linearly with the PTP1B activity in the range from 0.005 to 0.18 U mL(-1) with the lowest detection limit of 0.0017 U mL(-1). Moreover, using this proposed method, the inhibition effect of 6-chloro-3-formyl-7-methylchromone, betulinic acid, ursolic acid, and sodium orthovanadate on PTP1B activity can be tested with IC50 values of 10, 13, 9, and 1.1 MUM, respectively. Therefore, this new method has great potential not only for the detection of PTP1B activity but also for the screening of the inhibitors. PMID- 26153653 TI - Allergen stability of testing/treatment boards and immunotherapy vials with various diluents. AB - BACKGROUND: Otolaryngologists commonly use glycerin and normal saline with phenol (NSP) in diluting solutions to help preserve allergenicity in immunotherapy vials. Studies have shown that diluting with human serum albumin (HSA) may provide better allergen stability. The purpose of this study was to assess the ability of various diluents to preserve allergen content in testing/treatment boards (TTBs) and immunotherapy treatment vials (ITVs) at multiple time points. METHODS: TTBs with 4 allergens were prepared with HSA, NSP, 10% glycerin, and 50% glycerin. The major allergen content of the TTBs was measured at creation (time 0), 3 days, 8 weeks, and 18 weeks. Multiallergen ITVs containing the 4 allergens were prepared from the NSP board (diluted to 10% glycerin) and the HSA board (diluted in HSA) at the time of making the freshly prepared TTBs and again 8 weeks later, simulating the creation of ITVs from a "new" and an "old" TTB. The major allergen content of these ITVs was determined at creation and at interval time points thereafter. RESULTS: TTBs and ITVs showed a substantial loss of allergen at day 3. The loss of allergen was more pronounced in the more dilute (#4, #5, and #6) vials. HSA and 50% glycerin showed superior allergen preservation compared to NSP and 10% glycerin in TTBs. HSA showed superior allergen preservation compared to 10% glycerin-NSP in ITVs. CONCLUSION: The use of HSA as a diluent in TTBs and ITVs showed superior allergen preservation compared to NSP and 10% glycerin, particularly for more dilute vials. PMID- 26153654 TI - Blockade of BCL-2 proteins efficiently induces apoptosis in progenitor cells of high-risk myelodysplastic syndromes patients. AB - Deregulated apoptosis is an identifying feature of myelodysplastic syndromes (MDS). Whereas apoptosis is increased in the bone marrow (BM) of low-risk MDS patients, progression to high-risk MDS correlates with an acquired resistance to apoptosis and an aberrant expression of BCL-2 proteins. To overcome the acquired apoptotic resistance in high-risk MDS, we investigated the induction of apoptosis by inhibition of pro-survival BCL-2 proteins using the BCL-2/-XL/-W inhibitor ABT 737 or the BCL-2-selective inhibitor ABT-199. We characterized a cohort of 124 primary human BM samples from MDS/secondary acute myeloid leukemia (sAML) patients and 57 healthy, age-matched controls. Inhibition of anti-apoptotic BCL-2 proteins was specifically toxic for BM cells from high-risk MDS and sAML patients, whereas low-risk MDS or healthy controls remained unaffected. Notably, ABT-737 or ABT-199 treatment was capable of targeting the MDS stem/progenitor compartment in high-risk MDS/sAML samples as shown by the reduction in CD34(+) cells and the decreased colony-forming capacity. Elevated expression of MCL-1 conveyed resistance against both compounds. Protection by stromal cells only partially inhibited induction of apoptosis. Collectively, our data show that the apoptotic resistance observed in high-risk MDS/sAML cells can be overcome by the ABT-737 or ABT-199 treatment and implies that BH3 mimetics might delay disease progression in higher-risk MDS or sAML patients. PMID- 26153656 TI - Barriers to preventing unintended pregnancies and sexually transmitted infections as experienced by women in Fort Dauphin, southeast Madagascar. AB - OBJECTIVES: As part of a broader investigation into maternal and child health, this study aimed to explore barriers to preventing unintended pregnancies and sexually transmitted infections (STIs) for women in southeast Madagascar, in order to inform the development of interventions by a local non-governmental organisation. METHODS: A year-long mixed methods study was conducted. Qualitative information was obtained from 246 participants through focus groups, single-event and serial qualitative interviews. Quantitative data was collected through a closed-ended questionnaire with a sample of 373 women of reproductive age. Data was analysed using pre-determined and emerging themes. RESULTS: Family planning and sexual health services are not well integrated into other health services, nor routinely offered. Barriers to contraceptive use include actual or perceived side effects of hormonal methods, inaccurate information from health providers, and lack of support from partners or family members. STI prevalence is high, concurrent sexual relationships are common, and condom use is limited. CONCLUSIONS: Women's ability to prevent unintended pregnancies and STIs could be improved through measures aiming to dispel misconceptions about eligibility for and perceived risks of hormonal contraceptives, increase support for family planning among partners and families, and reframe the socio-cultural meaning of condom use in sexual relationships. PMID- 26153655 TI - Increased IL6 plasma levels in indolent systemic mastocytosis patients are associated with high risk of disease progression. AB - Systemic mastocytosis (SM) is a heterogeneous disease with altered interleukin (IL)-6 and IL13 plasma levels. However, no study has simultaneously investigated the plasma levels of IL1beta, IL6, IL13, CCL23 and clusterin in SM at diagnosis and correlated them with disease outcome. Here we investigated IL1beta, IL6, IL13, CCL23 and clusterin plasma levels in 75 SM patients--66 indolent SM (ISM) and 9 aggressive SM--and analyzed their prognostic impact among ISM cases grouped according to the extent of hematopoietic involvement of the bone marrow cells by the KIT D816V mutation. Although increased IL1beta, IL6 and CCL23 levels were detected in SM patients versus healthy controls, only IL6 and CCL23 levels gradually increased with disease severity. Moreover, increased IL6 plasma levels were associated with ISM progression to more aggressive disease, in particular among ISM patients with multilineal KIT mutation (ISM-ML), these patients also showing a higher frequency of organomegalies, versus other ISM-ML patients. Of note, all ISM patients who progressed had increased IL6 plasma levels already at diagnosis. Our results indicate that SM patients display an altered plasma cytokine profile already at diagnosis, increased IL6 plasma levels emerging as an early marker for disease progression among ISM cases, in particular among high risk ISM patients who carry multilineage KIT mutation. PMID- 26153657 TI - Determining the Conformational Landscape of sigma and pi Coupling Using para Phenylene and "Aviram-Ratner" Bridges. AB - The torsional dependence of donor-bridge-acceptor (D-B-A) electronic coupling matrix elements (H(DA), determined from the magnetic exchange coupling, J) involving a spin SD = 1/2 metal semiquinone (Zn-SQ) donor and a spin S(A) = 1/2 nitronylnitroxide (NN) acceptor mediated by the sigma/pi-systems of para phenylene and methyl-substituted para-phenylene bridges and by the sigma-system of a bicyclo[2.2.2]octane (BCO) bridge are presented and discussed. The positions of methyl group(s) on the phenylene bridge allow for an experimentally determined evaluation of conformationally dependent (pi) and conformationally independent (sigma) contributions to the electronic and magnetic exchange couplings in these D-B-A biradicals at parity of D and A. The trend in the experimental magnetic exchange couplings are well described by CASSCF calculations. The torsional dependence of the pairwise exchange interactions are further illuminated in three dimensional, "Ramachandran-type" plots that relate D-B and B-A torsions to both electronic and exchange couplings. Analysis of the magnetic data shows large variations in magnetic exchange (J ~ 1-175 cm(-1)) and electronic coupling (H(DA) ~ 450-6000 cm(-1)) as a function of bridge conformation relative to the donor and acceptor. This has allowed for an experimental determination of both the sigma- and pi-orbital contributions to the exchange and electronic couplings. PMID- 26153658 TI - Heterozygous ABCB4 mutations in children with cholestatic liver disease. AB - BACKGROUND & AIMS: Monoallelic defects in ABCB4, which encodes the canalicular floppase for phosphatidylcholine MDR3, have been encountered in association with a variety of hepatobiliary disorders, particularly in adult subjects. In this study, we examined the presence of heterozygous ABCB4 variants in a cohort of children with chronic cholestasis and assessed the pathogenicity of the missense changes identified. METHODS: Sixty-seven children with chronic liver dysfunction were studied by the sequencing of ABCB4 and multiplex ligation-dependent probe amplification analysis. The molecular defects arising from missense variants were analysed in MDCK-II and AD-293 cells. RESULTS: Defects in a single allele of ABCB4 were identified in nine subjects. They included one small insertion (p.I1242Nfs), one nonsense mutation (p.R144X) and six missense changes (p.T175A, p.G228R, p.A250T, p.S320F, p.P352L and p.A934T). In four children, these defects in ABCB4 co-existed with various medical conditions. In vitro phenotyping of the six missense variants revealed that four (T175A, G228R, S320F and A934T) led to reduced MDR3 protein levels. Two mutations (G228R and A934T) resulted in trapping of the protein in the endoplasmic reticulum. Phosphatidylcholine efflux activity was decreased to 56-18% of reference levels for MDR3 mutants T175A, A250T and S320F. The G228R, P352L and A934T mutants were found to be non-functional. CONCLUSIONS: These results illustrate the varying effects of ABCB4 missense mutations and suggest that even a modest reduction in MDR3 activity may contribute or predispose to the onset of cholestatic liver disease in the paediatric age. PMID- 26153659 TI - On the costs and benefits of repeating a nonspatial feature in an exogenous spatial cuing paradigm. AB - Recent research using the Posner cuing paradigm to explore inhibition of return seems to suggest that repetition of a nonspatial feature modulates cue-related facilitatory and inhibitory aftereffects differently in detection and discrimination tasks. Because the cues were unrelated to the final response in the detection task but parallel to (not orthogonal with) the final response in the discrimination task, it is unclear whether the different patterns of results were caused by the complexity of the decision (detection vs. discrimination) or by the task relevance of the feature that might or might not repeat from cue to target. Using a paradigm modeled on previous work, in Experiment 1 (detection task) and 2 (discrimination task) we replicated the previous patterns: No early feature repetition benefit but reduced IOR for feature mismatch trials in the detection task; and large early feature repetition benefit but no effect of feature match upon the later IOR in the discrimination task. In Experiment 3 (discrimination task), we used an "orthogonal-cuing" method: the feature (color) that could repeat or not from cue to target was not on the dimension being discriminated (shape). The pattern of results was very similar to what is observed in detection tasks. These results demonstrate that it is not the task but the task relevance of the repeating feature that modulates facilitation and inhibition effects. The findings are generally consistent with a habituation account of the inhibitory aftereffects of orienting but do not rule out the contribution of other mechanisms. PMID- 26153661 TI - A unique retinal epitheliopathy is associated with amyotrophic lateral sclerosis/Parkinsonism-Dementia complex of Guam. AB - BACKGROUND: The aim of this work was to examine whether a linear retinal pigment epitheliopathy is associated with the amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam. METHODS: A total of 918 Guamanian Chamorros, with and without amyotrophic lateral sclerosis/parkinsonism-dementia complex, were examined cross-sectionally for linear retinal pigment epitheliopathy (LRPE). Overall, 239 Guamanians, who were neurologically asymptomatic, were followed for up to 20 years to determine the risk of developing amyotrophic lateral sclerosis/parkinsonism-dementia complex. RESULTS: The epitheliopathy was present in 59.7% (117 of 196) patients with amyotrophic lateral sclerosis/parkinsonism dementia complex, but in only 24.7% (178 of 722) of subjects who were neurologically asymptomatic (age- and sex-adjusted risk difference: 35.0%; 95% confidence interval [CI]: 27.5-42.6; p < 0.0001). Prospectively, 15 of 50 cases with epitheliopathy developed amyotrophic lateral sclerosis/parkinsonism-dementia complex, compared to 4 of 189 cases without epitheliopathy (age- and sex-adjusted hazard ratio: 13.1; 95% CI: 4.0-43.1; P < 0.0001). CONCLUSION: Amyotrophic lateral sclerosis/parkinsonism-dementia complex is associated with an LRPE and predicts future neurological disease. Identifying the cause of this retinopathy could provide an understanding about the pathogenesis of amyotrophic lateral sclerosis/parkinsonism-dementia complex and related diseases. PMID- 26153662 TI - Studies on the Reaction of Iron(II) with NO in a Noncoordinating Ionic Liquid. AB - In an earlier study we investigated the reaction of iron(II) chloride with NO in a strongly coordinating ionic liquid 1-ethyl-3-methylimidazolium dicyanamide [emim][dca] and showed that the actual reactive species in solution was [Fe(II)(dca)5Cl](4-). For the present report we investigated in detail how this reaction could proceed in a noncoordinating ionic liquid 1-ethyl-3 methylimidazolium trifluoromethylsulfonate [emim][OTf]. The donor ability of OTf( ) is much lower than that of dca(-), such that the solubility of FeCl2 in [emim][OTf] strongly depended on other donors like water or chloride ions present or added to the ionic liquid. On increasing the chloride concentration in [emim][OTf], the tetrachloridoferrate complex [emim]2[FeCl4] was formed, as verified by X-ray crystallography. This complex undergoes reversible binding of NO, for which the UV-vis spectral characteristics of the green-brown nitrosyl product resembled that found for the corresponding nitrosyl complexes formed in water and [emim][dca] as solvents. A detailed analysis of the spectra revealed that the {Fe-NO}(7) species has Fe(II)-NO(*) character in contrast to Fe(III)-NO( ) as found for the other solvents. The formation constant, however, is much higher than in [emim][dca], lying closer to the value found for water as solvent. Surprisingly, the Mossbauer spectrum found in [emim][OTf] is very unusual and unsimilar to that found in water and [emim][dca] as solvents, pointing at a different electron density distribution between Fe and NO in {Fe-NO}.7 First, the high isomer shift points to the presence of iron(II) species in solution, thus indicating that upon NO binding no oxidation to iron(III) occurs. Second, the negligible quadrupole splitting suggests a high local symmetry around the iron center. The nitrosyl product is suggested to be [Fe(II)Cl3NO](-), which is supported by electron paramagnetic resonance (EPR) and IR measurements. The nature of the Fe(II) complexes formed in [emim][OTf] depends on the additives required to dissolve FeCl2 in this ionic liquid. PMID- 26153660 TI - Digital quantum simulation of fermionic models with a superconducting circuit. AB - One of the key applications of quantum information is simulating nature. Fermions are ubiquitous in nature, appearing in condensed matter systems, chemistry and high energy physics. However, universally simulating their interactions is arguably one of the largest challenges, because of the difficulties arising from anticommutativity. Here we use digital methods to construct the required arbitrary interactions, and perform quantum simulation of up to four fermionic modes with a superconducting quantum circuit. We employ in excess of 300 quantum logic gates, and reach fidelities that are consistent with a simple model of uncorrelated errors. The presented approach is in principle scalable to a larger number of modes, and arbitrary spatial dimensions. PMID- 26153663 TI - Validation of 2 Brief Fruit and Vegetable Assessment Instruments Among Third Grade Students. AB - OBJECTIVE: To evaluate the validity of 2 brief instruments to estimate fruit and vegetable (FV) intake among third-grade children. METHODS: Children from an elementary school and a community center (n = 107) completed 2 retrospective questions for FV intake (fruit and vegetable questionnaire [FVQ]) and a food record (A Day in the Life Questionnaire [DILQ]) to estimate FV intake. Agreement between intake based on these instruments and 3 24-hour dietary recalls was determined. RESULTS: Disattenuated Pearson correlation coefficients ranged from 0.40 to 0.69 for FV intake; however, the low reliability of multiple 24-hour recalls may have inflated the strength of the correlations. Altman-Bland difference plots suggested that the FVQ overestimated FV intake whereas the DILQ overestimated fruit and underestimated vegetable intake. Limits of agreement were wide for both tools, indicating poor overall agreement. CONCLUSIONS AND IMPLICATIONS: The FVQ and DILQ were not valid instruments to evaluate FV consumption under current study conditions. Other assessment methods and instruments should be considered for young children. PMID- 26153664 TI - Peer Review in Nursing: Essential Components of a Model Supporting Safety and Quality. AB - This article introduces an accountability-focused nursing framework to systematically organize and promote quality and safety nursing outcomes. The 4 essential components of this framework include a responsive environment; shared decision making, personal empowerment, and transformational management. These elements promote a professional practice environment that supports clinical nurses to practice at their highest level of autonomy and promotes accountability for patient outcomes. The often-misunderstood concept of peer review is foundational to 2 of the model components. PMID- 26153665 TI - Ferro-type order of magneto-electric quadrupoles as an order-parameter for the pseudo-gap phase of a cuprate superconductor. AB - There is general agreement within the community of researchers that investigate high-Tc materials that it is most important to understand the pseudo-gap phase. To this end, many experiments on various cuprates have been reported. Two prominent investigations-Kerr effect and neutron Bragg diffraction-imply that underdoped YBCO samples possess long-range magnetic order of an unusual kind. However, other measurements do not support the existence of magnetic order. Here we show that the Kerr effect and magnetic Bragg diffraction data are individual manifestations of ordered magneto-electric quadrupoles at Cu sites. While the use of magneto-electric multipoles is new in studies of the electronic properties of cuprates, they are not unknown in other materials, including an investigation with x-rays of the parent compound CuO. We exploit the recent prediction that neutrons are deflected by magneto-electric multipoles. The outcome of our study is a theory for the order-parameter of the pseudo-gap phase without the aforementioned conflict with other measurements, and the first experimental evidence that neutrons interact with multipoles belonging to a state of magnetic charge. PMID- 26153667 TI - Synthetic tools for studying the chemical biology of InsP8. AB - To synthesise stabilised mimics of InsP8, the most phosphorylated inositol phosphate signalling molecule in Nature, we replaced its two diphosphate (PP) groups with either phosphonoacetate (PA) or methylenebisphosphonate (PCP) groups. Utility of the PA and PCP analogues was verified by structural and biochemical analyses of their interactions with enzymes of InsP8 metabolism. PMID- 26153668 TI - Sex and Age Differences in Global Pain Status Among Patients Using Opioids Long Term for Chronic Noncancer Pain. AB - BACKGROUND: The use of chronic opioid therapy (COT) has risen dramatically in recent years, especially among women. However, little is known about factors influencing overall pain and function (global pain status) among COT users. Characterizing the typical experiences of COT patients by age-sex group could help clinicians and patients better weigh the risks and benefits of COT. Thus, we sought to characterize global pain status among COT users in community practice by age and sex. METHODS: Telephone survey of 2,163 health plan members aged 21-80 years using COT. We assessed average/usual pain (0-10 scale); pain-related interference (0-10); activity limitation days, last 3 months; and pain impact, last 2 weeks (0-11). Status on each indicator was classified as low (better pain/function), moderate, or high (worse pain/function). Global pain status was categorized as favorable if 2-4 indicators were low and 0-1 was high and unfavorable if 2-4 indicators were high and 0-1 was low. RESULTS: Among female COT patients, 15% (vs. 26% of males) had favorable global pain status and 59% (vs. 42% of males) had unfavorable status. Under age 65 years, women fared more poorly than men on every indicator. Among 65- to 80-year-olds, women and men had similar global pain status. CONCLUSIONS: Although pain and function among COT users vary considerably, only one in five reported low pain levels and high levels of function. Young and middle-aged women seem to be at particularly high risk for unfavorable global pain status. More research is needed about how to best manage pain in this group. PMID- 26153669 TI - Rates and determinants of hepatitis B 'e' antigen and hepatitis B surface antigen seroclearance during long-term follow-up of patients coinfected with HIV and hepatitis B virus. AB - OBJECTIVE: This study determines rates and risk factors associated with hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg) seroclearance, two important prognostic indicators during infection with hepatitis B virus (HBV), in a large contemporary cohort of patients coinfected with HIV-HBV. DESIGN: Prospective cohort study of predominately antiretroviral therapy (ART) experienced, coinfected patients. METHODS: Participants enrolled in the French HIV-HBV Cohort had complete HBV serological battery conducted at inclusion and every yearly visit. Piecewise-exponential survival models were used to determine risk factors associated with seroclearance. RESULTS: A total of 290 patients, of whom 151 (52.1%) were HBeAg positive, had been followed for a median 7.4 years (interquartile range [IQR] = 3.1-8.0). Tenofovir (TDF) containing ART became increasingly more frequent, as rates of undetectable HBV-DNA increased accordingly (at baseline = 39.3%, end of follow-up = 91.0%). In HBeAg-positive patients, 60 of 151 had HBeAg seroclearance (cumulative 46.4% at end of follow up) after a median 3.0 years (IQR = 2.0-4.9). Overall, 17 of 290 patients had HBsAg seroclearance (cumulative 7.4% at end of follow-up) after a median 4.6 years (IQR = 2.1-7.2). Lower levels of time-averaged cumulative HBV-DNA were significantly associated with both HBeAg and HBsAg seroclearance (P < 0.001 and P = 0.01, respectively). In post hoc analysis among patients initiating TDF, incidence rates of HBeAg seroclearance peaked at year 4 of TDF treatment (13.1/100 person-years), whereas a steep drop in HBsAg seroclearance incidence rates occurred after year 3 (at year 3 = 1.2/100 person-years versus thereafter = 0.6/100 person-years). CONCLUSION: HBsAg seroclearance and, to a lesser extent, HBeAg seroclearance remain difficult endpoints for patients coinfected with HIV HBV to achieve. HBV-DNA suppression, associated with effective treatment, is strongly linked to seroclearance, but this mostly occurs within the first years of ART-containing highly potent anti-HBV activity. PMID- 26153670 TI - Time of HIV diagnosis in infants after weaning from breast milk. AB - Of 28 infants diagnosed with HIV infections after the recommended time of breastfeeding cessation in a large clinical trial (the Breastfeeding, Antiretrovirals and Nutrition Study), 19 (68%) were first detected more than 6 weeks (and up to 168 days) after recommended weaning. The current WHO recommendation for HIV testing of infants is at 6 weeks or more after weaning; these data argue for repeat HIV testing of infants up to 6 months after breastfeeding cessation, so that no infant HIV infections are missed. PMID- 26153672 TI - Naturalistic Action Performance Distinguishes Amnestic Mild Cognitive Impairment from Healthy Aging. AB - Individuals with amnestic mild cognitive impairment (aMCI) show minor decrements in their instrumental activities of daily living (IADL). Sensitive measures of IADL performance are needed to capture the mild difficulties observed in aMCI groups. Routine naturalistic actions (NAs) are familiar IADL-type activities that require individuals to enact everyday tasks such as preparing coffee. In the current study we examined the extent to which NAs could be used to help facilitate differential diagnosis of aMCI relative to composite measures of episodic memory, semantic knowledge, and executive function. Healthy older adults (n=24) and individuals with aMCI (n=24) enacted two highly familiar NAs and completed tests of episodic memory, semantic knowledge, and executive function. Binary logistic regression was used to predict group membership (aMCI vs. control participants). The regression analyses indicated that NA performance could reliably predict group membership, over and above measures of cognitive functioning. These findings indicated that NA performance can be used to help facilitate differential diagnosis of healthy aging and aMCI and used as an outcome measure in intervention studies. PMID- 26153671 TI - Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding. AB - OBJECTIVE: The objective of this study is to determine whether detection of HIV infection was delayed in infants exposed to antiretroviral prophylaxis to prevent HIV transmission during breastfeeding. DESIGN: The Breastfeeding, Antiretrovirals and Nutrition (BAN) study was a randomized trial of 2369 mother-infant pairs conducted from 2004 to 2010. In addition to an intrapartum regimen, all mother infant pairs were randomly assigned to three antiretroviral intervention arms during 28 weeks of breastfeeding: no further antiretroviral prophylaxis (control arm); infant-daily nevirapine (nevirapine arm); and maternal zidovudine, lamivudine and either nevirapine, nelfinavir or lopinavir-ritonavir (maternal arm). After breastfeeding cessation counselling and stopping the antiretroviral interventions by 28 weeks, 28 infant HIV infections occurred. METHODS: To determine whether these infections occurred during the breastfeeding and antiretroviral intervention phase but had delayed detection on the antiretroviral arms, we performed ultrasensitive (droplet digital PCR) HIV testing on infants with stored peripheral blood mononuclear cell (PBMC) specimens at 24 weeks (n = 9). RESULTS: Of the nine infants, all three on the infant nevirapine arm had detectable HIV DNA at 24 weeks, compared with two of four on the maternal antiretroviral arm and one of two on the control arm. For infants with detectable HIV at 24 weeks, the median delay in detection between the ultrasensitive and standard assays was 18.3 weeks for the nevirapine arm, 15.4 weeks for the maternal arm and 9.4 weeks for the control arm. CONCLUSION: The prolonged inability to detect HIV with standard assays in the context of postnatal antiretroviral prophylaxis suggests that early antiretrovirals may restrict HIV replication sufficiently to lead to missed diagnosis among infected infants. Therefore, repeat virologic testing is warranted beyond the WHO-recommended point of testing at 6 weeks after breastfeeding cessation. PMID- 26153673 TI - 3D Printable Graphene Composite. AB - In human being's history, both the Iron Age and Silicon Age thrived after a matured massive processing technology was developed. Graphene is the most recent superior material which could potentially initialize another new material Age. However, while being exploited to its full extent, conventional processing methods fail to provide a link to today's personalization tide. New technology should be ushered in. Three-dimensional (3D) printing fills the missing linkage between graphene materials and the digital mainstream. Their alliance could generate additional stream to push the graphene revolution into a new phase. Here we demonstrate for the first time, a graphene composite, with a graphene loading up to 5.6 wt%, can be 3D printable into computer-designed models. The composite's linear thermal coefficient is below 75 ppm. degrees C(-1) from room temperature to its glass transition temperature (Tg), which is crucial to build minute thermal stress during the printing process. PMID- 26153674 TI - Bilayered construct for simultaneous regeneration of alveolar bone and periodontal ligament. AB - Periodontitis is an inflammatory disease that causes destruction of tooth supporting tissues and if left untreated leads to tooth loss. Current treatments have shown limited potential for simultaneous regeneration of the tooth supporting tissues. To recreate the complex architecture of the periodontium, we developed a bilayered construct consisting of poly(caprolactone) (PCL) multiscale electrospun membrane (to mimic and regenerate periodontal ligament, PDL) and a chitosan/2wt % CaSO4 scaffold (to mimic and regenerate alveolar bone). Scanning electron microscopy results showed the porous nature of the scaffold and formation of beadless electrospun multiscale fibers. The fiber diameter of microfiber and nanofibers was in the range of 10 +/- 3 um and 377 +/- 3 nm, respectively. The bilayered construct showed better protein adsorption compared to the control. Osteoblastic differentiation of human dental follicle stem cells (hDFCs) on chitosan/2wt % CaSO4 scaffold showed maximum alkaline phosphatase at seventh day followed by a decline thereafter when compared to chitosan control scaffold. Fibroblastic differentiation of hDFCs was confirmed by the expression of PLAP-1 and COL-1 proteins which were more prominent on PCL multiscale membrane in comparison to control membranes. Overall these results show that the developed bilayered construct might serve as a good candidate for the simultaneous regeneration of the alveolar bone and PDL. PMID- 26153675 TI - Healthcare utilization and costs among women diagnosed with uterine fibroids: a longitudinal evaluation for 5 years pre- and post-diagnosis. AB - OBJECTIVE: To evaluate the healthcare utilization, treatments, and costs incurred by women with uterine fibroids (UF), compared to those without UF, for 5 years before and 5 years after diagnosis. RESEARCH DESIGN AND METHODS: This is a longitudinal, retrospective case-control study. A total of 84,954 women with a diagnosis of UF, along with matched controls of women without UF, were selected from the Truven Health MarketScan claims database (2000-2010). The date of diagnosis of the UF patient was assigned as the index date for both the UF patient and her matched control. MAIN OUTCOME MEASURES: Healthcare resource utilization, treatments, and costs (in 2010 USD) were evaluated annually for the 5 year periods before and after the index date. RESULTS: UF patients had more outpatient and emergency room visits than controls before diagnosis, and more inpatient, outpatient, and emergency room visits than controls after diagnosis. Annual total healthcare costs were significantly higher for patients than controls during the last 3 years pre-index and all 5 years post-index. Overall, the difference was $12,623 over 10 years, with a difference of $1435 in the 5 years pre-diagnosis and a difference of $11,188 in the 5 years post-diagnosis. The cost difference between UF patients and controls was highest in the first year post-diagnosis, reaching $6131, and the difference was even larger when comparing clinically symptomatic UF patients to controls. The use of medications and surgical procedures related to UF peaked in the year post-diagnosis, with 39% of patients receiving a surgical treatment within the year. KEY LIMITATIONS: UF patients included in the study did not include undiagnosed and potentially asymptomatic UF patients; the impact of disease severity on the costs of UF patients was not evaluated. CONCLUSIONS: Patients with UF incurred significantly higher healthcare utilization and costs than those without UF, both pre- and post diagnosis. PMID- 26153676 TI - Posterior lumbar fixation in a kidney transplant recipient: logistics and perioperative challenges. AB - BACKGROUND: Kidney transplantation has become the ideal and successful treatment for medically suitable patients with established kidney disease. This results in increased likelihood of these patients developing unrelated conditions requiring surgery, including spinal surgery. There are only a few publications available regarding spinal patients with renal transplants. CASE REPORT: A 67-year-old patient presented with recurrent sciatica. Four years prior to this, he received a living donor kidney transplant. He was diagnosed with right L4 radiculopathy due to recurrent foraminal stenosis as a result of the grade I L4/5 spondylolisthesis. He was offered a reoperation including microdecompression and postero-lateral fixation and fusion. The renal transplant necessitated specific pre- and intraoperative considerations. The knee-chest position with extra padding was used to maintain the region of the renal transplant free from any pressure. The renal care was planned in detail by the transplant surgeons and nephrologists and shared with the ward doctors and on-call teams. The procedure was uneventful; there were no signs of intraoperative or postoperative acute renal injury. The patient was discharged 5 days postoperatively; all renal parameters remained within normal ranges and the postoperative plain films demonstrated satisfactory surgical results. CONCLUSIONS: The key to success was a multidisciplinary approach and detailed planning regarding pre-, intra- and postoperative care. The presented scheme of care might be useful when considering the posterior approach and prone positioning in kidney transplant recipients with spinal pathologies requiring surgical treatment. PMID- 26153677 TI - Expert's comment concerning Grand Rounds case entitled "Posterior lumbar fixation in a kidney transplant recipient-logistics and perioperative challenges" (Marcin Czyz, Sibylle Jurgens, Keith M. Rigg, Marrie O'Connor, Bronek M. Boszczyk). PMID- 26153678 TI - Letter to the Editor concerning "Comparison of unilateral versus bilateral pedicle screw fixation in lumbar interbody fusion: a meta-analysis" by W. Ding et al. (2014) Eur Spine J 23(2):395-403. PMID- 26153679 TI - The prevalence of degenerative or incidental findings in the lumbar spine of pediatric patients: a study using magnetic resonance imaging as a screening tool. AB - PURPOSE: Several studies using magnetic resonance imaging (MRI) to evaluate the lumbar spine in adults have shown a large prevalence of degenerative changes in asymptomatic subjects; however, studies in pediatric patients are scarce. Those studies have suggested a lower rate of degenerative findings in adolescents than in adults, but the actual prevalence of MRI findings in the pediatric population has not yet been determined. We aimed to determine the prevalence of degenerative changes in the lumbar spine of pediatric patients using abdominal and pelvic MRI as the screening tool. METHODS: We studied 103 patients (mean age 6.6 years) who were evaluated with abdominal and pelvic MRI for indications that were not spine related. The entire lumbo-sacral spine was evaluated to detect the presence of disc degeneration (DD), disc displacement, anular rupture with high-intensity zone (HIZ) and Modic changes. RESULTS: In our population, 10.7 % [4.9-16.5] had at least one disc classified as Pfirrmann 2, and no patients presented discs classified as Pfirrmann 3, 4 or 5; patients exhibiting discs classified as Pfirrmann 2 were significantly older than patients who had only Pfirrmann 1 discs. The prevalence of disc bulging was 1 % [0-2.9]. No patients presented disc herniation (including protrusion or extrusions); additionally, no patients exhibited HIZ or Modic changes. CONCLUSIONS: Incidental findings related to DD are very uncommon at this early age, in contrast to findings described in adults or later in adolescence. PMID- 26153681 TI - Correction: Methodological discussion about prevalence of the dental fluorosis on dental health surveys. PMID- 26153680 TI - Gestational marginal zinc deficiency impaired fetal neural progenitor cell proliferation by disrupting the ERK1/2 signaling pathway. AB - This study investigated if a marginal zinc deficiency during gestation in rats could affect fetal neural progenitor cell (NPC) proliferation through a down regulation of the extracellular signal-regulated kinase (ERK1/2) signaling pathway. Rats were fed a marginally zinc-deficient or adequate diet from the beginning of gestation until embryonic day (E)19. The proportion of proliferating cells in the E19 fetal ventricular zone was decreased by marginal zinc deficiency. Immunostaining for phosphorylated ERK1/2 in the cerebral cortex was decreased in the marginal zinc fetuses, and this effect was strongest in the ventricular zone. Furthermore, phosphorylation of the upstream mitogen-activated ERK kinases (MEK1/2) was not affected, suggesting that marginal zinc deficiency could have increased ERK-directed phosphatase activity. Similar findings were observed in cultured rat embryonic cortical neurons and in IMR-32 neuroblastoma cells, in which zinc-deficiency decreased ERK1/2 phosphorylation without affecting MEK1/2 phosphorylation. Indeed, zinc deficiency increased the activity of the ERK-directed phosphatase protein phosphatase 2A (PP2A) in the fetal cortex and IMR-32 cells. Inhibition of PP2A with okadaic acid prevented the decrease in ERK phosphorylation and proliferation of zinc-deficient IMR-32 cells. Together these results demonstrated that decreased zinc availability reduces ERK1/2 signaling and decreased NPC proliferation as a consequence of PP2A activation. Disruption of fetal neurogenesis could underlie irreversible neurobehavioral impairments observed after even marginal zinc nutrition during a critical period of early brain development. PMID- 26153684 TI - Catalytic dioxygenation of flavonol by M(II)-complexes (M = Mn, Fe, Co, Ni, Cu and Zn) - mimicking the M(II)-substituted quercetin 2,3-dioxygenase. AB - In order to get insights into the metal ion effects and the carboxylate effects on enzymatic activity, a series of the carboxylate ligand supported transition metal complexes [M(II)L(OAc)] (M = Mn (), Fe (), Co (), Ni (), Cu () and Zn (); LH = 2-{[bis-(pyridin-2-ylmethyl)amino]methyl}-4-methoxy benzoic acid) were synthesized and characterized as structural and functional models for the active sites of various M(II)-substituted resting quercetin 2,3-dioxygenases (2,3-QD). Their structures, spectroscopic features, redox properties, as well as the catalytic reactivity toward the substrate flavonol and O2 have been investigated in detail. The model complexes show higher enzymatic reactivities in the catalytic dioxygenation (oxidative ring opening) of the substrate flavonol at lower temperatures (55-100 degrees C), presumably caused by the carboxylate group in the supporting model ligand, which could lower the redox potential of the bound substrate flavonolate by electron donation. The catalytic reactivity of [M(II)L(OAc)] exhibits notable differences and it is in a metal ion dependent order of Co () > Ni () > Zn () > Fe () > Mn () > Cu (). The differences in the reactivities among them could be ascribed to the redox potential of the bound substrate flavonolate, which was drastically influenced by the metal ions via tuning the electron density of flavonolate, providing important insights into the metal ion effects and the carboxylate effects on the enzymatic activity of various M(II)-substituted 2,3-QD. Our model complexes [M(II)L(OAc)] are the first examples of a series of structural and functional models of various M(II) substituted resting 2,3-QD. PMID- 26153685 TI - EDITORIAL. PMID- 26153682 TI - Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice. AB - We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. PMID- 26153686 TI - Late Adulthood: Perspectives on Human Development. PMID- 26153687 TI - A Difference-In-Differences Study of the Effects of a New Abandoned Building Remediation Strategy on Safety. AB - Vacant and abandoned buildings pose significant challenges to the health and safety of communities. In 2011 the City of Philadelphia began enforcing a Doors and Windows Ordinance that required property owners of abandoned buildings to install working doors and windows in all structural openings or face significant fines. We tested the effects of the new ordinance on the occurrence of crime surrounding abandoned buildings from January 2011 to April 2013 using a difference-in-differences approach. We used Poisson regression models to compare differences in pre- and post-treatment measures of crime for buildings that were remediated as a result of the ordinance (n = 676) or permitted for renovation (n = 241), and randomly-matched control buildings that were not remediated (n = 676) or permitted for renovation (n = 964), while also controlling for sociodemographic and other confounders measured around each building. Building remediations were significantly associated with citywide reductions in overall crimes, total assaults, gun assaults and nuisance crimes (p < 0.001). Building remediations were also significantly associated with reductions in violent gun crimes in one city section (p < 0.01). At the same time, some significant increases were seen in narcotics sales and possession and property crimes around remediated buildings (p < 0.001). Building renovation permits were significantly associated with reductions in all crime classifications across multiple city sections (p < 0.001). We found no significant spatial displacement effects. Doors and windows remediation offers a relatively low-cost method of reducing certain crimes in and around abandoned buildings. Cities with an abundance of decaying and abandoned housing stock might consider some form of this structural change to their built environments as one strategy to enhance public safety. PMID- 26153688 TI - Highly Conductive Aromatic Functionalized Multi-Walled Carbon Nanotube for Inkjet Printable High Performance Supercapacitor Electrodes. AB - We report the functionalization of multiwalled carbon nanotubes (MWCNT) via the 1,3-dipolar [3+2] cycloaddition of aromatic azides, which resulted in a detangled CNT as shown by transmission electron microscopy (TEM). Carboxylic moieties ( COOH) on aromatic azide result in highly stable aqueous dispersion (max. conc. ~ 10 mg/mL H2O), making the suitable for inkjet printing. Printed patterns on polyethylene terephthalate (PET) flexible substrate exhibit low sheet resistivity ~65 Omega. cm, which is attributed to enhanced conductivity. Fabricated Supercapacitors (SC) assembled using these printed substrates exhibit good electrochemical performance in organic as well as aqueous electrolytes. High energy and power density (57.8 Wh/kg and 0.85 kW/kg) in 1M H2SO4 aqueous electrolyte demonstrate the excellent performance of the proposed supercapacitor. Capacitive retention varies from ~85-94% with columbic efficiency ~95% after 1000 charge/discharge cycles in different electrolytes, demonstrating the excellent potential of the device for futuristic power applications. PMID- 26153689 TI - First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs. AB - Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older. PMID- 26153690 TI - Correction: Epidemic process over the commute network in a metropolitan area. PMID- 26153691 TI - Bats Swarm Where They Hibernate: Compositional Similarity between Autumn Swarming and Winter Hibernation Assemblages at Five Underground Sites. AB - During autumn in the temperate zone of both the new and old world, bats of many species assemble at underground sites in a behaviour known as swarming. Autumn swarming behaviour is thought to primarily serve as a promiscuous mating system, but may also be related to the localization and assessment of hibernacula. Bats subsequently make use of the same underground sites during winter hibernation, however it is currently unknown if the assemblages that make use of a site are comparable across swarming and hibernation seasons. Our purpose was to characterize the bat assemblages found at five underground sites during both the swarming and the hibernation season and compare the assemblages found during the two seasons both across sites and within species. We found that the relative abundance of individual species per site, as well as the relative proportion of a species that makes use of each site, were both significantly correlated between the swarming and hibernation seasons. These results suggest that swarming may indeed play a role in the localization of suitable hibernation sites. Additionally, these findings have important conservation implications, as this correlation can be used to improve monitoring of underground sites and predict the importance of certain sites for rare and cryptic bat species. PMID- 26153692 TI - Conization Using an Electrosurgical Knife for Cervical Intraepithelial Neoplasia and Microinvasive Carcinoma. AB - OBJECTIVE: The aim of the present study was to evaluate the incidences of margin involvement, disease relapse, and complications in patients who had undergone conization using an electrosurgical knife (EKC) for cervical intraepithelial neoplasia (CIN) or microinvasive carcinomas (micro-CAs). MATERIALS AND METHODS: A retrospective case series analysis was performed with a total of 1359 patients who underwent EKC in Fudan University Shanghai Cancer Center between June 2004 and July 2010. RESULTS: The median age of the patients was 39 years old (range: 19-72). Conization revealed the presence of CIN in 1113 (81.9%) patients, micro CA in 72 (5.3%) patients and invasive carcinomas in 44 (3.2%) patients. The remaining 130 (9.6%) patients were free of diseases in the cone specimens. Positive surgical margins, or endocervical curettages (ECCs) were found in 90 (7.6%) patients with CINs or micro-CAs. Three factors were associated with positive margins and ECCs and included age (>50 years; odds ratio (OR), 3.0, P<0.01), postmenopausal status (OR, 3.1, P<0.01) and microinvasive disease (OR, 2.7, P<0.01). One thousand and eighty-nine (92.0%) patients were followed-up regularly for a median follow-up duration of 46 months (range: 24-106 months). Disease relapse was documented in 50 (4.6%) patients. Eighty-two (6.0%) cases experienced surgical complications that needed to be addressed, including early or late hemorrhages, infections, cervical stenosis, etc. CONCLUSIONS: Our patients demonstrated that EKC was an alternative technique for diagnosis and treatment of CIN or micro-CAs with relatively low rate of recurrence and acceptable rate of complications. A randomized clinical trial is warranted to compare EKC, CKC and LEEP in the management of CIN or micro-CA. PMID- 26153693 TI - Operational Tree Species Mapping in a Diverse Tropical Forest with Airborne Imaging Spectroscopy. AB - Remote identification and mapping of canopy tree species can contribute valuable information towards our understanding of ecosystem biodiversity and function over large spatial scales. However, the extreme challenges posed by highly diverse, closed-canopy tropical forests have prevented automated remote species mapping of non-flowering tree crowns in these ecosystems. We set out to identify individuals of three focal canopy tree species amongst a diverse background of tree and liana species on Barro Colorado Island, Panama, using airborne imaging spectroscopy data. First, we compared two leading single-class classification methods--binary support vector machine (SVM) and biased SVM--for their performance in identifying pixels of a single focal species. From this comparison we determined that biased SVM was more precise and created a multi-species classification model by combining the three biased SVM models. This model was applied to the imagery to identify pixels belonging to the three focal species and the prediction results were then processed to create a map of focal species crown objects. Crown-level cross-validation of the training data indicated that the multi-species classification model had pixel-level producer's accuracies of 94-97% for the three focal species, and field validation of the predicted crown objects indicated that these had user's accuracies of 94-100%. Our results demonstrate the ability of high spatial and spectral resolution remote sensing to accurately detect non-flowering crowns of focal species within a diverse tropical forest. We attribute the success of our model to recent classification and mapping techniques adapted to species detection in diverse closed-canopy forests, which can pave the way for remote species mapping in a wider variety of ecosystems. PMID- 26153694 TI - An Integrated Morphological and Molecular Approach to the Description and Systematisation of a Novel Genus and Species of Macrodasyida (Gastrotricha). AB - BACKGROUND: Gastrotricha systematics is in a state of flux mainly due to the conflicts between cladistic studies base on molecular markers and the classical systematisation based on morphological traits. In sandy samples from Thailand, we found numerous macrodasyidan gastrotrichs belonging to an undescribed species of difficult taxonomic affiliation. The abundance and original nature of the specimens prompted us to undertake a deep survey of both morphological and molecular traits aiming at a reliable systematisation of the new taxon. METHODOLOGY/PRINCIPAL FINDINGS: Using several microscopical techniques we investigated the external and internal anatomy, including the muscular and nervous systems of the new species. Additional specimens were used to obtain the 18S rRNA gene sequence; molecular data was analysed cladistically in conjunction with data from additional species belonging to the near complete Macrodasyida taxonomic spectrum. Specimens are vermiform, up to 806 MUm in total length, and show a well-defined head equipped with peculiar leaf-like sensorial organs and a single-lobed posterior end. The adhesive apparatus includes anterior, ventrolateral, dorsal and posterior tubes. Pharynx is about 1/4 of the total length and shows pores at its posterior 3/4. Adult specimens exhibit maturing eggs and a bulky, muscular caudal organ, but do not show sperm nor the frontal organ. Musculature and nervous system organisation resemble the usual macrodasyidan plan; however, the somatic circular muscles of the intestinal region surround all other muscular components and a third FMRFamide-IR commissure ventral to the pharyngo-intestinal junction appear to be an autoapomorphic traits of the new species. CONCLUSIONS/SIGNIFICANCE: While the anatomical characteristics of the Asian specimens appear so unique to grant the establishment of a new taxon, for which the name Thaidasys tongiorgii gen. et sp. nov. is proposed, the result of phylogenetic analyses based on the 18S rRNA gene unites the new genus with the family Macrodasyidae. PMID- 26153695 TI - Get your kICS by measuring membrane protein dynamics. PMID- 26153696 TI - Dual-color 3D superresolution microscopy by combined spectral-demixing and biplane imaging. AB - Multicolor three-dimensional (3D) superresolution techniques allow important insight into the relative organization of cellular structures. While a number of innovative solutions have emerged, multicolor 3D techniques still face significant technical challenges. In this Letter we provide a straightforward approach to single-molecule localization microscopy imaging in three dimensions and two colors. We combine biplane imaging and spectral-demixing, which eliminates a number of problems, including color cross-talk, chromatic aberration effects, and problems with color registration. We present 3D dual-color images of nanoscopic structures in hippocampal neurons with a 3D compound resolution routinely achieved only in a single color. PMID- 26153697 TI - Inferring diffusion dynamics from FCS in heterogeneous nuclear environments. AB - Fluorescence correlation spectroscopy (FCS) is a noninvasive technique that probes the diffusion dynamics of proteins down to single-molecule sensitivity in living cells. Critical mechanistic insight is often drawn from FCS experiments by fitting the resulting time-intensity correlation function, G(t), to known diffusion models. When simple models fail, the complex diffusion dynamics of proteins within heterogeneous cellular environments can be fit to anomalous diffusion models with adjustable anomalous exponents. Here, we take a different approach. We use the maximum entropy method to show-first using synthetic data that a model for proteins diffusing while stochastically binding/unbinding to various affinity sites in living cells gives rise to a G(t) that could otherwise be equally well fit using anomalous diffusion models. We explain the mechanistic insight derived from our method. In particular, using real FCS data, we describe how the effects of cell crowding and binding to affinity sites manifest themselves in the behavior of G(t). Our focus is on the diffusive behavior of an engineered protein in 1) the heterochromatin region of the cell's nucleus as well as 2) in the cell's cytoplasm and 3) in solution. The protein consists of the basic region-leucine zipper (BZip) domain of the CCAAT/enhancer-binding protein (C/EBP) fused to fluorescent proteins. PMID- 26153698 TI - Mechanical properties of a primary cilium as measured by resonant oscillation. AB - Primary cilia are ubiquitous mammalian cellular substructures implicated in an ever-increasing number of regulatory pathways. The well-established ciliary hypothesis states that physical bending of the cilium (for example, due to fluid flow) initiates signaling cascades, yet the mechanical properties of the cilium remain incompletely measured, resulting in confusion regarding the biological significance of flow-induced ciliary mechanotransduction. In this work we measure the mechanical properties of a primary cilium by using an optical trap to induce resonant oscillation of the structure. Our data indicate 1) the primary cilium is not a simple cantilevered beam; 2) the base of the cilium may be modeled as a nonlinear rotatory spring, with the linear spring constant k of the cilium base calculated to be (4.6 +/- 0.62) * 10(-12) N/rad and nonlinear spring constant alpha to be (-1 +/- 0.34) * 10(-10) N/rad(2); and 3) the ciliary base may be an essential regulator of mechanotransduction signaling. Our method is also particularly suited to measure mechanical properties of nodal cilia, stereocilia, and motile cilia-anatomically similar structures with very different physiological functions. PMID- 26153699 TI - Microconstriction arrays for high-throughput quantitative measurements of cell mechanical properties. AB - We describe a method for quantifying the mechanical properties of cells in suspension with a microfluidic device consisting of a parallel array of micron sized constrictions. Using a high-speed charge-coupled device camera, we measure the flow speed, cell deformation, and entry time into the constrictions of several hundred cells per minute during their passage through the device. From the flow speed and the occupation state of the microconstriction array with cells, the driving pressure across each constriction is continuously computed. Cell entry times into microconstrictions decrease with increased driving pressure and decreased cell size according to a power law. From this power-law relationship, the cell elasticity and fluidity can be estimated. When cells are treated with drugs that depolymerize or stabilize the cytoskeleton or the nucleus, elasticity and fluidity data from all treatments collapse onto a master curve. Power-law rheology and collapse onto a master curve are predicted by the theory of soft glassy materials and have been previously shown to describe the mechanical behavior of cells adhering to a substrate. Our finding that this theory also applies to cells in suspension provides the foundation for a quantitative high-throughput measurement of cell mechanical properties with microfluidic devices. PMID- 26153700 TI - A computational model of dynein activation patterns that can explain nodal cilia rotation. AB - Normal left-right patterning in vertebrates depends on the rotational movement of nodal cilia. In order to produce this ciliary motion, the activity of axonemal dyneins must be tightly regulated in a temporal and spatial manner; the specific activation pattern of the dynein motors in the nodal cilia has not been reported. Contemporary imaging techniques cannot directly assess dynein activity in a living cilium. In this study, we establish a three-dimensional model to mimic the ciliary ultrastructure and assume that the activation of dynein proteins is related to the interdoublet distance. By employing finite-element analysis and grid deformation techniques, we simulate the mechanical function of dyneins by pairs of point loads, investigate the time-variant interdoublet distance, and simulate the dynein-triggered ciliary motion. The computational results indicate that, to produce the rotational movement of nodal cilia, the dynein activity is transferred clockwise (looking from the tip) between the nine doublet microtubules, and along each microtubule, the dynein activation should occur faster at the basal region and slower when it is close to the ciliary tip. Moreover, the time cost by all the dyneins along one microtubule to be activated can be used to deduce the dynein activation pattern; it implies that, as an alternative method, measuring this time can indirectly reveal the dynein activity. The proposed protein-structure model can simulate the ciliary motion triggered by various dynein activation patterns explicitly and may contribute to furthering the studies on axonemal dynein activity. PMID- 26153701 TI - Biomechanical and structural features of CS2 fimbriae of enterotoxigenic Escherichia coli. AB - Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrhea worldwide, and infection of children in under-developed countries often leads to high mortality rates. Isolated ETEC expresses a plethora of colonization factors (fimbriae/pili), of which CFA/I and CFA/II, which are assembled via the alternate chaperone pathway (ACP), are among the most common. Fimbriae are filamentous structures whose shafts are primarily composed of helically arranged single pilin protein subunits, with a unique biomechanical ability to unwind and rewind. A sustained ETEC infection, under adverse conditions of dynamic shear forces, is primarily attributed to this biomechanical feature of ETEC fimbriae. Recent understanding about the role of fimbriae as virulence factors points to an evolutionary adaptation of their structural and biomechanical features. In this work, we investigated the biophysical properties of CS2 fimbriae from the CFA/II group. Homology modeling of its major structural subunit, CotA, reveals structural clues related to the niche in which they are expressed. Using optical tweezers force spectroscopy, we found that CS2 fimbriae unwind at a constant force of 10 pN and have a corner velocity (i.e., the velocity at which the force required for unwinding rises exponentially with increased speed) of 1300 nm/s. The biophysical properties of CS2 fimbriae assessed in this work classify them into a low-force unwinding group of fimbriae together with the CFA/I and CS20 fimbriae expressed by ETEC strains. The three fimbriae are expressed by ETEC, colonize in similar gut environments, and exhibit similar biophysical features, but differ in their biogenesis. Our observation suggests that the environment has a strong impact on the biophysical characteristics of fimbriae expressed by ETEC. PMID- 26153702 TI - The cytoskeleton regulates cell attachment strength. AB - Quantitative information about adhesion strength is a fundamental part of our understanding of cell-extracellular matrix (ECM) interactions. Adhesion assays should measure integrin-ECM bond strength, but reports now suggest that cell components remain behind after exposure to acute force for radial shear assays in the presence of divalent cations that increase integrin-ECM affinity. Here, we show that focal adhesion proteins FAK, paxillin, and vinculin but not the cytoskeletal protein actin remain behind after shear-induced detachment of HT1080 fibrosarcoma cells. Cytoskeletal stabilization increased attachment strength by eightfold, whereas cross-linking integrins to the substrate only caused a 1.5 fold increase. Reducing temperature-only during shear application-also increased attachment strength eightfold, with detachment again occurring between focal adhesion proteins and actin. Detachment at the focal adhesion-cytoskeleton interface was also observed in mouse and human fibroblasts and was ligand independent, highlighting the ubiquity of this mode of detachment in the presence of divalent cations. These data show that the cytoskeleton and its dynamic coupling to focal adhesions are critically important for cell adhesion in niche with divalent cations. PMID- 26153703 TI - Conformational transitions in the glycine-bound GluN1 NMDA receptor LBD via single-molecule FRET. AB - The N-methyl-D-aspartate receptor (NMDAR) is a member of the glutamate receptor family of proteins and is responsible for excitatory transmission. Activation of the receptor is thought to be controlled by conformational changes in the ligand binding domain (LBD); however, glutamate receptor LBDs can occupy multiple conformations even in the activated form. This work probes equilibrium transitions among NMDAR LBD conformations by monitoring the distance across the glycine-bound LBD cleft using single-molecule Forster resonance energy transfer (smFRET). Recent improvements in photoprotection solutions allowed us to monitor transitions among the multiple conformations. Also, we applied a recently developed model-free algorithm called "step transition and state identification" to identify the number of states, their smFRET efficiencies, and their interstate kinetics. Reversible interstate conversions, corresponding to transitions among a wide range of cleft widths, were identified in the glycine-bound LBD, on much longer timescales compared to channel opening. These transitions were confirmed to be equilibrium in nature by shifting the distribution reversibly via denaturant. We found that the NMDAR LBD proceeds primarily from one adjacent smFRET state to the next under equilibrium conditions, consistent with a cleft opening/closing mechanism. Overall, by analyzing the state-to-state transition dynamics and distributions, we achieve insight into specifics of long-lived LBD equilibrium structural dynamics, as well as obtain a more general description of equilibrium folding/unfolding in a conformationally dynamic protein. The relationship between such long-lived LBD dynamics and channel function in the full receptor remains an open and interesting question. PMID- 26153704 TI - Synaptobrevin transmembrane domain influences exocytosis by perturbing vesicle membrane curvature. AB - Membrane fusion requires that nearly flat lipid bilayers deform into shapes with very high curvature. This makes membrane bending a critical force in determining fusion mechanisms. A lipid bilayer will bend spontaneously when material is distributed asymmetrically between its two monolayers, and its spontaneous curvature (C0) will influence the stability of curved fusion intermediates. Prior work on Ca(2+)-triggered exocytosis revealed that fusion pore lifetime (tau) varies with vesicle content (Q), and showed that this relation reflects membrane bending energetics. Lipids that alter C0 change the dependence of tau on Q. These results suggested that the greater stability of an initial exocytotic fusion pore associated with larger vesicles reflects the need to bend more membrane during fusion pore dilation. In this study, we explored the possibility of manipulating C0 by mutating the transmembrane domain (TMD) of the vesicle membrane protein synaptobrevin 2 (syb2). Amperometric measurements of exocytosis in mouse chromaffin cells revealed that syb2 TMD mutations altered the relation between tau and Q. The effects of these mutations showed a striking periodicity, changing sign as the structural perturbation moved through the inner and outer leaflets. Some glycine and charge mutations also influenced the dependence of tau on Q in a manner consistent with expected changes in C0. These results suggest that side chains in the syb2 TMD influence the kinetics of exocytosis by perturbing the packing of the surrounding lipids. The present results support the view that membrane bending occurs during fusion pore expansion rather than during fusion pore formation. This supports the view of an initial fusion pore through two relatively flat membranes formed by protein. PMID- 26153705 TI - Cholesterol modulates CFTR confinement in the plasma membrane of primary epithelial cells. AB - The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that, when mutated, causes the disease cystic fibrosis. Although CFTR has been detected in a detergent-resistant membrane fraction prepared from airway epithelial cells, suggesting that it may partition into cholesterol-rich membrane microdomains (lipid rafts), its compartmentalization has not been demonstrated in intact cells and the influence of microdomains on CFTR lateral mobility is unknown. We used live-cell imaging, spatial image correlation spectroscopy, and k-space image correlation spectroscopy to examine the aggregation state of CFTR and its dynamics both within and outside microdomains in the plasma membrane of primary human bronchial epithelial cells. These studies were also performed during treatments that augment or deplete membrane cholesterol. We found two populations of CFTR molecules that were distinguishable based on their dynamics at the cell surface. One population showed confinement and had slow dynamics that were highly cholesterol dependent. The other, more abundant population was less confined and diffused more rapidly. Treatments that deplete the membrane of cholesterol caused the confined fraction and average number of CFTR molecules per cluster to decrease. Elevating cholesterol had the opposite effect, increasing channel aggregation and the fraction of channels displaying confinement, consistent with CFTR recruitment into cholesterol-rich microdomains with dimensions below the optical resolution limit. Viral infection caused the nanoscale microdomains to fuse into large platforms and reduced CFTR mobility. To our knowledge, these results provide the first biophysical evidence for multiple CFTR populations and have implications for regulation of their surface expression and channel function. PMID- 26153706 TI - Hydrophobic surfactant proteins strongly induce negative curvature. AB - The hydrophobic surfactant proteins SP-B and SP-C greatly accelerate the adsorption of vesicles containing the surfactant lipids to form a film that lowers the surface tension of the air/water interface in the lungs. Pulmonary surfactant enters the interface by a process analogous to the fusion of two vesicles. As with fusion, several factors affect adsorption according to how they alter the curvature of lipid leaflets, suggesting that adsorption proceeds via a rate-limiting structure with negative curvature, in which the hydrophilic face of the phospholipid leaflets is concave. In the studies reported here, we tested whether the surfactant proteins might promote adsorption by inducing lipids to adopt a more negative curvature, closer to the configuration of the hypothetical intermediate. Our experiments used x-ray diffraction to determine how the proteins in their physiological ratio affect the radius of cylindrical monolayers in the negatively curved, inverse hexagonal phase. With binary mixtures of dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC), the proteins produced a dose-related effect on curvature that depended on the phospholipid composition. With DOPE alone, the proteins produced no change. With an increasing mol fraction of DOPC, the response to the proteins increased, reaching a maximum 50% reduction in cylindrical radius at 5% (w/w) protein. This change represented a doubling of curvature at the outer cylindrical surface. The change in spontaneous curvature, defined at approximately the level of the glycerol group, would be greater. Analysis of the results in terms of a Langmuir model for binding to a surface suggests that the effect of the lipids is consistent with a change in the maximum binding capacity. Our findings show that surfactant proteins can promote negative curvature, and support the possibility that they facilitate adsorption by that mechanism. PMID- 26153707 TI - Tuning membrane thickness fluctuations in model lipid bilayers. AB - Membrane thickness fluctuations have been associated with a variety of critical membrane phenomena, such as cellular exchange, pore formation, and protein binding, which are intimately related to cell functionality and effective pharmaceuticals. Therefore, understanding how these fluctuations are controlled can remarkably impact medical applications involving selective macromolecule binding and efficient cellular drug intake. Interestingly, previous reports on single-component bilayers show almost identical thickness fluctuation patterns for all investigated lipid tail-lengths, with similar temperature-independent membrane thickness fluctuation amplitude in the fluid phase and a rapid suppression of fluctuations upon transition to the gel phase. Presumably, in vivo functions require a tunability of these parameters, suggesting that more complex model systems are necessary. In this study, we explore lipid tail-length mismatch as a regulator for membrane fluctuations. Unilamellar vesicles of an equimolar mixture of dimyristoylphosphatidylcholine and distearoylphosphatidylcholine molecules, with different tail-lengths and melting transition temperatures, are used as a model system for this next level of complexity. Indeed, this binary system exhibits a significant response of membrane dynamics to thermal variations. The system also suggests a decoupling of the amplitude and the relaxation time of the membrane thickness fluctuations, implying a potential for independent control of these two key parameters. PMID- 26153708 TI - Single-molecule folding mechanisms of the apo- and Mg(2+)-bound states of human neuronal calcium sensor-1. AB - Neuronal calcium sensor-1 (NCS-1) is the primordial member of a family of proteins responsible primarily for sensing changes in neuronal Ca(2+) concentration. NCS-1 is a multispecific protein interacting with a number of binding partners in both calcium-dependent and independent manners, and acting in a variety of cellular processes in which it has been linked to a number of disorders such as schizophrenia and autism. Despite extensive studies on the Ca(2+)-activated state of NCS proteins, little is known about the conformational dynamics of the Mg(2+)-bound and apo states, both of which are populated, at least transiently, at resting Ca(2+) conditions. Here, we used optical tweezers to study the folding behavior of individual NCS-1 molecules in the presence of Mg(2+) and in the absence of divalent ions. Under tension, the Mg(2+)-bound state of NCS-1 unfolds and refolds in a three-state process by populating one intermediate state consisting of a folded C-domain and an unfolded N-domain. The interconversion at equilibrium between the different molecular states populated by NCS-1 was monitored in real time through constant-force measurements and the energy landscapes underlying the observed transitions were reconstructed through hidden Markov model analysis. Unlike what has been observed with the Ca(2+)-bound state, the presence of Mg(2+) allows both the N- and C-domain to fold through all or-none transitions with similar refolding rates. In the absence of divalent ions, NCS-1 unfolds and refolds reversibly in a two-state reaction involving only the C-domain, whereas the N-domain has no detectable transitions. Overall, the results allowed us to trace the progression of NCS-1 folding along its energy landscapes and provided a solid platform for understanding the conformational dynamics of similar EF-hand proteins. PMID- 26153709 TI - Effects of hydrophobic macromolecular crowders on amyloid beta (16-22) aggregation. AB - In Alzheimer's disease (AD), the amyloid beta (Abeta) peptide aggregates in the brain to form progressively larger oligomers, fibrils, and plaques. The aggregation process is strongly influenced by the presence of other macromolecular species, called crowders, that can exert forces on the proteins. One very common attribute of macromolecular crowders is their hydrophobicity. We examined the effect of hydrophobic crowders on protein aggregation by using discontinuous molecular dynamics (DMD) simulations in combination with an intermediate resolution protein model, PRIME20. The systems considered contained 48 Abeta (16-22) peptides and crowders with diameters of 5 A, 20 A, and 40 A, represented by hard spheres or spheres with square-well/square-shoulder interactions, at a crowder volume fraction of phi = 0.10. Results show that low levels of crowder hydrophobicity are capable of increasing the fibrillation lag time and high levels of crowder hydrophobicity can fully prevent the formation of fibrils. The types of structures that remain during the final stages of the simulations are summarized in a global phase diagram that shows fibril, disordered oligomer, or beta-sheet phases in the space spanned by crowder size and crowder hydrophobicity. In particular, at high levels of hydrophobicity, simulations with 5 A crowders result in only disordered oligomers and simulations with 40 A crowders result in only beta-sheets. The presence of hydrophobic crowders reduces the antiparallel beta-sheet content of fibrils, whereas hard sphere crowders increase it. Finally, strong hydrophobic crowders alter the secondary structure of the Abeta (16-22) monomers, bending them into a shape that is incapable of forming ordered beta-sheets or fibrils. These results qualitatively agree with previous theoretical and experimental work. PMID- 26153710 TI - Thermodynamics of long supercoiled molecules: insights from highly efficient Monte Carlo simulations. AB - Supercoiled DNA polymer models for which the torsional energy depends on the total twist of molecules (Tw) are a priori well suited for thermodynamic analysis of long molecules. So far, nevertheless, the exact determination of Tw in these models has been based on a computation of the writhe of the molecules (Wr) by exploiting the conservation of the linking number, Lk=Tw+Wr, which reflects topological constraints coming from the helical nature of DNA. Because Wr is equal to the number of times the main axis of a DNA molecule winds around itself, current Monte Carlo algorithms have a quadratic time complexity, O(L(2)), with respect to the contour length (L) of the molecules. Here, we present an efficient method to compute Tw exactly, leading in principle to algorithms with a linear complexity, which in practice is O(L(1.2)). Specifically, we use a discrete wormlike chain that includes the explicit double-helix structure of DNA and where the linking number is conserved by continuously preventing the generation of twist between any two consecutive cylinders of the discretized chain. As an application, we show that long (up to 21 kbp) linear molecules stretched by mechanical forces akin to magnetic tweezers contain, in the buckling regime, multiple and branched plectonemes that often coexist with curls and helices, and whose length and number are in good agreement with experiments. By attaching the ends of the molecules to a reservoir of twists with which these can exchange helix turns, we also show how to compute the torques in these models. As an example, we report values that are in good agreement with experiments and that concern the longest molecules that have been studied so far (16 kbp). PMID- 26153711 TI - Its preferential interactions with biopolymers account for diverse observed effects of trehalose. AB - Biopolymer homeostasis underlies the health of organisms, and protective osmolytes have emerged as one strategy used by Nature to preserve biopolymer homeostasis. However, a great deal remains unknown about the mechanism of action of osmolytes. Trehalose, as a prominent example, stabilizes proteins against denaturation by extreme temperature and denaturants, preserves membrane integrity upon freezing or in dry conditions, inhibits polyQ-mediated protein aggregation, and suppresses the aggregation of denatured proteins. The underlying thermodynamic mechanisms of such diverse effects of trehalose remain unclear or controversial. In this study, we applied the surface-additive method developed in the Record laboratory to attack this issue. We characterized the key features of trehalose-biopolymer preferential interactions and found that trehalose has strong unfavorable interactions with aliphatic carbon and significant favorable interactions with amide/anionic oxygen. This dissection has allowed us to elucidate the diverse effects of trehalose and to identify the crucial functional group(s) responsible for its effects. With (semi)quantitative thermodynamic analysis, we discovered that 1) the unfavorable interaction of trehalose with hydrophobic surfaces is the dominant factor in its effect on protein stability, 2) the favorable interaction of trehalose with polar amides enables it to inhibit polyQ-mediated protein aggregation and the aggregation of denatured protein in general, and 3) the favorable interaction of trehalose with phosphate oxygens, together with its unfavorable interaction with aliphatic carbons, enables trehalose to preserve membrane integrity in aqueous solution. These results provide a basis for a full understanding of the role of trehalose in biopolymer homeostasis and the reason behind its evolutionary selection as an osmolyte, as well as for a better application of trehalose as a chemical chaperone. PMID- 26153712 TI - From discrete to continuum models of three-dimensional deformations in epithelial sheets. AB - Epithelial tissue, in which cells adhere tightly to each other and to the underlying substrate, is one of the four major tissue types in adult organisms. In embryos, epithelial sheets serve as versatile substrates during the formation of developing organs. Some aspects of epithelial morphogenesis can be adequately described using vertex models, in which the two-dimensional arrangement of epithelial cells is approximated by a polygonal lattice with an energy that has contributions reflecting the properties of individual cells and their interactions. Previous studies with such models have largely focused on dynamics confined to two spatial dimensions and analyzed them numerically. We show how these models can be extended to account for three-dimensional deformations and studied analytically. Starting from the extended model, we derive a continuum plate description of cell sheets, in which the effective tissue properties, such as bending rigidity, are related explicitly to the parameters of the vertex model. To derive the continuum plate model, we duly take into account a microscopic shift between the two sublattices of the hexagonal network, which has been ignored in previous work. As an application of the continuum model, we analyze tissue buckling by a line tension applied along a circular contour, a simplified set-up relevant to several situations in the developmental contexts. The buckling thresholds predicted by the continuum description are in good agreement with the results of stability calculations based on the vertex model. Our results establish a direct connection between discrete and continuum descriptions of cell sheets and can be used to probe a wide range of morphogenetic processes in epithelial tissues. PMID- 26153713 TI - Predicting first traversal times for virions and nanoparticles in mucus with slowed diffusion. AB - Particle-tracking experiments focusing on virions or nanoparticles in mucus have measured mean-square displacements and reported diffusion coefficients that are orders of magnitude smaller than the diffusion coefficients of such particles in water. Accurate description of this subdiffusion is important to properly estimate the likelihood of virions traversing the mucus boundary layer and infecting cells in the epithelium. However, there are several candidate models for diffusion that can fit experimental measurements of mean-square displacements. We show that these models yield very different estimates for the time taken for subdiffusive virions to traverse through a mucus layer. We explain why fits of subdiffusive mean-square displacements to standard diffusion models may be misleading. Relevant to human immunodeficiency virus infection, using computational methods for fractional subdiffusion, we show that subdiffusion in normal acidic mucus provides a more effective barrier against infection than previously thought. By contrast, the neutralization of the mucus by alkaline semen, after sexual intercourse, allows virions to cross the mucus layer and reach the epithelium in a short timeframe. The computed barrier protection from fractional subdiffusion is some orders of magnitude greater than that derived by fitting standard models of diffusion to subdiffusive data. PMID- 26153718 TI - Electrochemiluminescence Resonance Energy Transfer System: Mechanism and Application in Ratiometric Aptasensor for Lead Ion. AB - In this paper, a novel electrochemiluminescence resonance energy transfer (ECL RET) system from O2/S2O8(2-) to a kind of amino-terminated perylene derivative (PTC-NH2) was demonstrated for the first time, which was then applied to construct a ratiometric aptasensor for lead ion (Pb(2+)) detection. First, gold nanoparticles-functionalized fullerene nanocomposites (AuNPs@nano-C60) were coated on a glassy carbon electrode (GCE), and then thiol-modified assistant probes (APs) were attached on AuNPs@nano-C60/GCE. Then the resultant electrode was hybridized with capture probes (the aptamer of the Pb(2+), abbreviated as CPs) to generate DNA duplexes, which could induce PTC-NH2 to be intercalated into the dsDNA grooves by the electrostatic adsorption. Herein, ECL dual peaks at -0.7 V (vs Ag/AgCl) and -2.0 V (vs Ag/AgCl) were obtained when the prepared aptasensor was detected in air-saturated S2O8(2-) solution, which could be attributed to the emission of excited dimmers (pi-excimers) ((1)(NH2-PTC)2*) and (1)(O2)2*, respectively. In the presence of Pb(2+), the dsDNA was unwound, and Pb(2+) G quadruplex structure was generated because of the highly specific affinity between Pb(2+) and CPs, which made the PTC-NH2 release from the electrode surface. As a result, the ECL signal at -0.7 V was decreased, and the ECL signal around -2.0 V was increased. By measuring the ratio of ECL intensities at two excitation potentials, the developed aptasensor exhibited the linear response range from 1.0 * 10(-12) M to 1.0 * 10(-7) M with a detection limit of 3.5 * 10( 13) M (S/N = 3) for Pb(2+), which could offer an alternative analytical method with excellent properties of high selectivity, accuracy, and sensitivity. PMID- 26153715 TI - Novel Azido-Iodo Photoaffinity Ligands for the Human Serotonin Transporter Based on the Selective Serotonin Reuptake Inhibitor (S)-Citalopram. AB - Three photoaffinity ligands (PALs) for the human serotonin transporter (hSERT) were synthesized based on the selective serotonin reuptake inhibitor (SSRI), (S) citalopram (1). The classic 4-azido-3-iodo-phenyl group was appended to either the C-1 or C-5 position of the parent molecule, with variable-length linkers, to generate ligands 15, 22, and 26. These ligands retained high to moderate affinity binding (K(i) = 24-227 nM) for hSERT, as assessed by [(3)H]5-HT transport inhibition. When tested against Ser438Thr hSERT, all three PALs showed dramatic rightward shifts in inhibitory potency, with Ki values ranging from 3.8 to 9.9 MUM, consistent with the role of Ser438 as a key residue for high-affinity binding of many SSRIs, including (S)-citalopram. Photoactivation studies demonstrated irreversible adduction to hSERT by all ligands, but the reduced (S) citalopram inhibition of labeling by [(125)I]15 compared to that by [(125)I]22 and [(125)I]26 suggests differences in binding mode(s). These radioligands will be useful for characterizing the drug-protein binding interactions for (S) citalopram at hSERT. PMID- 26153719 TI - Ion-Responsive Channels of Zwitterion-Carbon Nanotube Membrane for Rapid Water Permeation and Ultrahigh Mono-/Multivalent Ion Selectivity. AB - The rational combination of polymer matrix and nanostructured building blocks leads to the formation of composite membranes with unexpected capability of selectivity of monovalent electrolytes and water, which affords the feasibility to effeciently remove harmful ions and neutral molecules from the environment of concentrated salines. However, the multivalent ion rejection in salined water of routine nanocomposite membranes was less than 98% when ion strength is high, resulting in a poor ion selectivity far below the acceptable value. In this contribution, the ion-responsive membrane with zwitterion-carbon nanotube (ZCNT) entrances at the surface and nanochannels inside membrane has been proposed to obtain ultrahigh multivalent ion rejection. The mean effective pore diameter of ZCNT membrane was dedicated tuned from 1.24 to 0.54 nm with the rise in Na2SO4 concentration from 0 to 70 mol m(-3) as contrary to the conventional rejection drop in carbon nanotube (CNT) membrane. The ultrahigh selective permeabilities of monovalent anions against divalent anions of 93 and against glucose of 5.5 were obtained on ZCNT membrane, while such selectivities were only 20 and 1.6 for the pristine CNT membrane, respectively. The ZCNT membranes have potential applications in treatment of salined water with general NaCl concentration from 100 to 600 mol m(-3), which are widely applicable in desalination, food, and biological separation processes. PMID- 26153720 TI - Synthesis and Characterization of a Two Stage, Nonlinear Photobase Generator. AB - Amine photobase generators (PBGs) are uncommon yet useful compounds. Rarer still are examples of PBGs that are active at visible wavelengths. We report the synthesis and characterization of new photolabile amine protecting groups that are active under visible light. The new chromophore, benzothiophene imino phenylacetonitrile (BTIPA), was synthesized in four steps without use of chromatography and found to release any one of several amines upon exposure to 405 nm light. The chromophore was also demonstrated to be useful as a Merrifield synthesis protecting group. Experimental evidence suggests a sequential, two stage photolysis mechanism which leads to a nonlinear response to dose. PMID- 26153721 TI - Full-Scale Modeling Explaining Large Spatial Variations of Nitrous Oxide Fluxes in a Step-Feed Plug-Flow Wastewater Treatment Reactor. AB - Nitrous oxide (N2O) emission data collected from wastewater treatment plants (WWTPs) show huge variations between plants and within one plant (both spatially and temporarily). Such variations and the relative contributions of various N2O production pathways are not fully understood. This study applied a previously established N2O model incorporating two currently known N2O production pathways by ammonia-oxidizing bacteria (AOB) (namely the AOB denitrification and the hydroxylamine pathways) and the N2O production pathway by heterotrophic denitrifiers to describe and provide insights into the large spatial variations of N2O fluxes in a step-feed full-scale activated sludge plant. The model was calibrated and validated by comparing simulation results with 40 days of N2O emission monitoring data as well as other water quality parameters from the plant. The model demonstrated that the relatively high biomass specific nitrogen loading rate in the Second Step of the reactor was responsible for the much higher N2O fluxes from this section. The results further revealed the AOB denitrification pathway decreased and the NH2OH oxidation pathway increased along the path of both Steps due to the increasing dissolved oxygen concentration. The overall N2O emission from this step-feed WWTP would be largely mitigated if 30% of the returned sludge were returned to the Second Step to reduce its biomass nitrogen loading rate. PMID- 26153722 TI - Therapeutic Potential of Multipotent Mesenchymal Stromal Cells and Their Extracellular Vesicles. AB - The therapeutic potential of mesenchymal stromal cells (MSCs) is evident by the number of new and ongoing trials targeting an impressive variety of conditions. In bone and cartilage repair, MSCs are expected to replace the damaged tissue, while in other therapies they modulate a therapeutic response by the secretion of bioactive molecules. MSCs possess a phenotypic plasticity and harbor an arsenal of bioactive molecules that can be released upon sensing signals in the local milieu either directly or packaged in extracellular vesicles (EVs). The reported paracrine effects comprise many of the important functions of MSCs, including supporting hematopoietic stem cells in the bone marrow, promoting angiogenesis, and modulating the immune system. The major drawback in MSC therapy is the incomplete understanding of cell fate following systemic administration as well as the mechanisms by which these cells correct disease. In this review we discuss what is known about MSC engraftment, hemocompatibility, and immunomodulation, as well as the potential of bringing the MSC-EV field toward a clinical translation. PMID- 26153723 TI - Unique Regulation of the Melatonin Synthetic Pathway in the Retina of Diurnal Female Arvicanthis ansorgei (Rodentia). AB - Knowledge about melatonin synthesis and its potential roles within the retina remains fragmented, especially in mammals where studies have focused on the penultimate enzyme of melatonin synthesis arylalkylamine N-acetyltransferase (AA NAT), whereas the final enzyme necessary for melatonin production is hydroxyindole-O-methytransferase (HIOMT). We explored multiple parameters of the melatonin synthetic pathway in the cone-rich retina of a diurnal rodent, Arvicanthis ansorgei, cones being previously implicated as probable reservoirs of melatonin production. We analyzed the temporal and spatial expression of Aa-nat mRNA and AA-NAT protein and enzymatic activity of AA-NAT, HIOMT, as well as the melatonin receptor type 1 and melatonin itself. We report that Aa-nat mRNA was localized principally to cones and ganglion cells (retinal ganglion cell [RGC]) with opposing cyclic expression, being maximal in cones during the night, and maximal in RGC in the daytime. AA-NAT protein was also immunolocalized to these same populations, and was present and active throughout the 24-hour period. HIOMT immunolocalization mirrored that of AA-NAT, but expression levels and activity were extremely low and remained uniform throughout the 24-hour period. MT1 showed a complementary expression pattern to the synthetic enzymes, present in rod photoreceptors, some inner retinal neurons and RGC. Surprisingly, melatonin levels were consistently low throughout the day/night cycle, in accordance with the low activity levels of HIOMT. These data demonstrate that the melatonin synthetic pathway in a diurnal rodent differs from that described for other tissues and species (nocturnal and diurnal), the contrasting phase expression in photoreceptors and RGC, suggesting distinct roles in these populations. PMID- 26153724 TI - Cyanobacterial Inhabitation on Archean Rock Surfaces in the Pilbara Craton, Western Australia. AB - High abundances of 7- and 6-monomethylalkanes as well as C17 n-alkane, indicative of cyanobacteria, have been discovered near the surfaces of Archean carbonate rocks of the Fortescue Group in the Pilbara region, Western Australia. The presence of cyanobacterial biomarkers is mostly limited to the surface layer (<1 cm thickness) of the rocks, indicating that the cyanobacteria are an endolithic species. Biomarkers are found in bitumen I (solvent-extracted rock) and also in bitumen II (solvent-extracted decarbonated rock). The abundance of biomarkers is generally the same between both bitumen fractions in the surface layer, which suggests that the cyanobacteria penetrated into the carbonate minerals. Trace amounts of the biomarkers have also diffused into a deeper part of the rocks, but this influence is only seen in bitumen I. This implies that hydrocarbons moved toward the inside of the rock through pores and fissures in the rock fabric. In contrast, hydrocarbons in bitumen II, which mainly come from within the carbonate minerals, are isolated from the hydrocarbon migration from the outside of the rock and may be ancient indigenous organic matter. To the best of our knowledge, this is the first report of the past or modern inhabitation of cyanobacteria on Archean rocks in the Pilbara region for which hydrocarbon biomarker analyses was used. PMID- 26153725 TI - Amyloid-beta as a biomarker for Alzheimer's disease: quantification methods in body fluids. AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by neuronal impairment leading to dramatic changes in brain. Amyloid-beta peptides and tau protein are the most promising biomarkers for AD. Cerebrospinal fluid and plasma are used to determine the concentration of these species. Since the pathological processes of AD start decades before the first symptoms, biomarkers may provide the possibility of early disease detection. The application of rapidly emerging technology, such as mass spectrometry, has opened new avenues to accelerate biomarker discovery, both for diagnostic as well as for prognostic purposes. This review summarizes AD biomarker studies with focus on amyloid-beta peptides in biological fluids and their quantification with immunoassays as well as the latest mass spectrometry-based methods. PMID- 26153727 TI - Electronic phase transitions in ultrathin magnetite films. AB - Magnetite (Fe3O4) shows singular electronic and magnetic properties, resulting from complex electron-electron and electron-phonon interactions that involve the interplay of charge, orbital and spin degrees of freedom. The Verwey transition is a manifestation of these interactions, with a puzzling connection between the low temperature charge ordered state and the dynamic charge fluctuations still present above the transition temperature. Here we explore how these rich physical phenomena are affected by thin film geometries, particularly focusing on the ultimate size limit defined by thicknesses below the minimum bulk unit cell. On one hand, we address the influence of extended defects, such as surfaces or antiphase domains, on the novel features exhibited by thin films. On the other, we try to isolate the effect of the reduced thickness on the electronic and magnetic properties. We will show that a distinct phase diagram and novel charge distributions emerge under reduced dimensions, while holding the local high magnetic moments. Altogether, thin film geometries offer unique possibilities to understand the complex interplay of short- and long-range orders in the Verwey transition. Furthermore, they arise as interesting candidates for the exploitation of the rich physics of magnetite in devices that demand nanoscale geometries, additionally offering novel functionalities based on their distinct properties with respect to the bulk form. PMID- 26153728 TI - Maternal physical morbidity associated with denial of pregnancy. AB - BACKGROUND: Denial of pregnancy, an inappropriate reaction where the woman does not consciously recognise her pregnancy, has been widely associated with poor outcomes for the woman's mental health, the events of labour and the newborn's health. However, reports of maternal physical complications are rare. AIMS: To evaluate the physical morbidity associated with denial of pregnancy. MATERIALS AND METHODS: Birth records from 2007 to 2013 were searched for women who did not receive any antenatal care. The medical records of women with denial of pregnancy were then examined in detail. The primary outcome measure was physical morbidity in women with denial of pregnancy until labour, using the hospital's general obstetric population as a comparator. RESULTS: Six cases of denial of pregnancy (involving five women) were identified, a rate of 1:1420 births. All characteristics and complications were in keeping with previous studies, except regarding maternal physical morbidity. Three of the five women experienced physical complications, namely pre-eclampsia and its sequelae. Concerningly, two of these women required admission to the intensive care unit, one after an eclamptic seizure. These complications were significantly higher than in the hospital's wider obstetric population (all P < 0.05). CONCLUSIONS: Previous reports of low maternal physical morbidity associated with denial of pregnancy are likely a reflection of low rates of diagnosis and underreporting. Given this study's increased rate of maternal physical morbidity and the implications this has for the women's future pregnancies, this underlines the importance of actively considering physical complications in women presenting with denial of pregnancy. PMID- 26153729 TI - Juvenile Traumatic Brain Injury Increases Alcohol Consumption and Reward in Female Mice. AB - Traumatic brain injury (TBI) is closely and bi-directionally linked with alcohol use, as by some estimates intoxication is the direct or indirect cause of one third to one-half of all TBI cases. Alcohol use following injury can reduce the efficacy of rehabilitation and increase the chances for additional injury. Finally, TBI itself may be a risk factor for the development of alcohol use disorders. Children who suffer TBIs have poorer life outcomes and more risk of substance abuse. We used a standardized closed-head injury to model mild traumatic brain injuries. We found that mice injured as juveniles but not during adulthood exhibited much greater alcohol self-administration in adulthood. Further, this phenomenon was limited to female mice. Using behavioral testing, including conditioned place preference assays, we showed that early injuries increase the rewarding properties of alcohol. Environmental enrichment administered after injury reduced axonal degeneration and prevented the increase in drinking behavior. Additionally, brain-derived neurotrophic factor gene expression, which was reduced by TBI, was normalized by environmental enrichment. Together, these results suggest a novel model of alterations in reward circuitry following trauma during development. PMID- 26153726 TI - Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol. AB - Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis alpha1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define chronic obstructive pulmonary disease (COPD) phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; and blood microRNA and blood mononuclear cell RNA and DNA profiling. We will rely on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off alpha-1 antitrypsin augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from the Subpopulations and Intermediate Outcome Measures in COPD Study who match on FEV1 and age will be compared. In the primary analysis, we will determine if the PiZZ individuals on augmentation therapy have a difference in lower respiratory tract microbes identified compared with matched PiZZ individuals who are not on augmentation therapy. By characterizing the microbiome in alpha-1 antitrypsin deficiency (AATD), we hope to define new phenotypes of COPD that explain some of the diversity of clinical presentations. As a unique genetic cause of COPD, AATD may inform typical COPD pathogenesis, and better understanding of it may illuminate the complex interplay between environment and genetics. Although the biologic approaches are hypothesis generating, the results may lead to development of novel biomarkers, better understanding of COPD phenotypes, and development of novel diagnostic and therapeutic trials in AATD and COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01832220). PMID- 26153730 TI - Editorial Comment to Palonosetron with aprepitant plus dexamethasone to prevent chemotherapy-induced nausea and vomiting during gemcitabine/cisplatin in urothelial cancer patients. PMID- 26153731 TI - Abuse-Deterrent Formulations of Prescription Opioids. PMID- 26153733 TI - Differentially Addressable Cavities within Metal-Organic Cage-Cross-Linked Polymeric Hydrogels. AB - Here we report a new class of hydrogels formed by polymers that are cross-linked through subcomponent self-assembled metal-organic cages. Selective encapsulation of guest molecules within the cages creates two distinct internal phases within the hydrogel, which allows for contrasting release profiles of related molecules depending on their aptitude for encapsulation within the cages. The hydrogels were fabricated into microparticles via a droplet-based microfluidic approach and proved responsive to a variety of stimuli, including acid and competing amine or aldehyde subcomponents, allowing for the triggered release of cargo. PMID- 26153734 TI - Comparison effects of dietary iron dextran and bacterial-iron supplementation on growth performance, fecal microbial flora, and blood profiles in sows and their litters. AB - This study was conducted to compare effects of dietary administration of iron dextran and bacterial-iron on growth performance, fecal microbial flora, and blood profiles in sows and their litters. A total of 20 multiparous sows (Landrace * Yorkshire) were randomly allotted into two treatments: (i) ID (basal diet, piglets were injected with iron dextran); (ii) BR (basal diet + bacterial iron; bacterial-iron was given to sows, piglets were not injected with iron dextran). There were five replicates per treatment with two sows per replicate. No differences were observed on sow and piglet growth performance, fecal microbial flora as well as sow blood profiles between ID and BR treatments. In piglets, blood iron, red blood cell and hemoglobin concentrations in ID treatment were higher (P < 0.05) on days 12 and 24. Furthermore, concentration of white blood cells in BR treatment was lower (P < 0.05) on day 12. However, the percentage of lymphocytes on day 12 was increased (P < 0.05) in BR treatment. In conclusion, effect of iron dextran and bacterial-iron has no difference on growth performance in lactating sows and piglets, but iron dextran injection has higher blood iron, white blood cell, red blood cell and hemoglobin concentrations in piglets. PMID- 26153732 TI - Natural bone fragmentation in the blind cave-dwelling fish, Astyanax mexicanus: candidate gene identification through integrative comparative genomics. AB - Animals that colonize dark and nutrient-poor subterranean environments evolve numerous extreme phenotypes. These include dramatic changes to the craniofacial complex, many of which are under genetic control. These phenotypes can demonstrate asymmetric genetic signals wherein a QTL is detected on one side of the face but not the other. The causative gene(s) underlying QTL are difficult to identify with limited genomic resources. We approached this task by searching for candidate genes mediating fragmentation of the third suborbital bone (SO3) directly inferior to the orbit of the eye. We integrated positional genomic information using emerging Astyanax resources, and linked these intervals to homologous (syntenic) regions of the Danio rerio genome. We identified a discrete, approximately 6 Mb, conserved region wherein the gene causing SO3 fragmentation likely resides. We interrogated this interval for genes demonstrating significant differential expression using mRNA-seq analysis of cave and surface morphs across life history. We then assessed genes with known roles in craniofacial evolution and development based on GO term annotation. Finally, we screened coding sequence alterations in this region, identifying two key genes: transforming growth factor beta3 (tgfb3) and bone morphogenetic protein 4 (bmp4). Of these candidates, tgfb3 is most promising as it demonstrates significant differential expression across multiple stages of development, maps close (<1 Mb) to the fragmentation critical locus, and is implicated in a variety of other animal systems (including humans) in non-syndromic clefting and malformations of the cranial sutures. Both abnormalities are analogous to the failure-to-fuse phenotype that we observe in SO3 fragmentation. This integrative approach will enable discovery of the causative genetic lesions leading to complex craniofacial features analogous to human craniofacial disorders. This work underscores the value of cave-dwelling fish as a powerful evolutionary model of craniofacial disease, and demonstrates the power of integrative system-level studies for informing the genetic basis of craniofacial aberrations in nature. PMID- 26153735 TI - Contraception Use, Abortions, and Births: The Effect of Insurance Mandates. AB - Beginning August, 2012, the U.S. Patient Protection and Affordable Care Act (ACA) required new private health insurance plans to cover contraceptive methods and counseling without requiring an insured's copay. The ACA represents the first instance of federally mandated contraception insurance coverage, but 30 U.S. states had already mandated contraceptive insurance coverage through state-level legislation prior to the ACA. This study examines whether mandated insurance coverage of contraception affects contraception use, abortions, and births. I find that mandates increase the likelihood of contraception use by 2.1 percentage points, decrease the abortion rate by 3 %, and have an insignificant impact on the birth rate. The results imply a lower-bound estimate that the ACA will result in approximately 25,000 fewer abortions. PMID- 26153736 TI - Midterm Results of Sternal Band Closure in Open Heart Surgery and Risk Analysis of Sternal Band Removal. AB - Sternal dehiscence, which is responsible for the development of mediastinitis, is a serious complication after cardiothoracic surgery. We retrospectively compared the results of two methods for sternal closure after cardiothoracic surgery performed during January 2009 to May 2012. The methods comprised closure with sternal bands and steel wires (group A, n = 92) versus conventional closure using steel wires alone (group B, n = 442). Although not significantly different between the two groups, no patients undergoing sternal band closure experienced dehiscence or mediastinitis. The incidence of having to remove materials used for sternal closure was significantly higher in group A than in group B. In each case of removal in group A, the materials removed were sternal bands whose tips had caused direct cutaneous irritation. Thus, although sternal bands may be effective for rigid sternal closure, they must sometimes be removed because of chest discomfort caused by the tip of the band. PMID- 26153737 TI - Identification of a new marine algal species Pyropia nitida sp. nov. (Bangiales: Rhodophyta) from Monterey, California. AB - An unidentified marine red algal species classified in Pyropia J. Agardh was discovered from Monterey, CA. Morphological, barcode, and complete mitochondrial genome analysis of the alga support its recognition as a new species, Pyropia nitida sp. nov. The species is a high-intertidal, winter annual that is lanceolate in shape, monostromatic, and dioecious. Based on CO1 sequences, P. nitida is closely allied with the P. nereocystis clade. The mitogenome of P. nitida is 35 313 bp in length and contains 53 genes, including two ribosomal RNAs, 24 transfer RNAs, four ribosomal proteins, two ymfs, four ORFs, and 17 genes involved in electron transport and oxidative phosphorylation. The results support the recognition of P. nitida as distinct from the morphologically similar P. lanceolata. PMID- 26153738 TI - Complete mitochondrial genome of Cygnus olor (Aves, Anseriformes, Anatidae). AB - The complete mitochondrial genome of Cygnus olor (Aves, Anseriformes, Anatidae) was revealed in this study. Total 16 739 base pairs (bp) of this mitogenome encoded genes for 13 protein coding genes (PCGs), two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and a D-loop (control region). The 12S rRNA and 16S rRNA genes are located between tRNA-Phe and tRNA-Leu (UUR) and segmentalized by the tRNA-Val. D-loop is located between tRNA-Glu and tRNA-Phe. The overall base composition of C. olor is G + C: 47.8%, A + T: 52.2%, apparently with a slight AT bias. Following the phylogenetic analysis, the C. olor was closed to Anser cygnoides. PMID- 26153739 TI - The complete chloroplast genome of the Dendrobium strongylanthum (Orchidaceae: Epidendroideae). AB - Complete chloroplast genome sequence is very useful for studying the phylogenetic and evolution of species. In this study, the complete chloroplast genome of Dendrobium strongylanthum was constructed from whole-genome Illumina sequencing data. The chloroplast genome is 153 058 bp in length with 37.6% GC content and consists of two inverted repeats (IRs) of 26 316 bp. The IR regions are separated by large single-copy region (LSC, 85 836 bp) and small single-copy (SSC, 14 590 bp) region. A total of 130 chloroplast genes were successfully annotated, including 84 protein coding genes, 38 tRNA genes, and eight rRNA genes. Phylogenetic analyses showed that the chloroplast genome of Dendrobium strongylanthum is related to that of the Dendrobium officinal. PMID- 26153740 TI - Sequencing and analysis of the whole mitochondrial genome of a variegated racerunner from Taklamakan Desert. AB - The whole mitochondrial genome of a variegated racerunner (Eremias vermiculata) from the Taklamakan Desert was determined using polymerase chain reaction and directly sequenced with a primer walking method. The mitogenome sequence was 19 796 bp in size, containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region (D-loop), which is similar to the typical mtDNA of vertebrates. Mitochondrial genomes analyses using maximum parsimony and Bayesian analyses yielded identical phylogenetic trees, indicating a close phylogenetic affinity of the seven Eremias species. Monophyly of the genus Eremias and E. vermiculata was recovered. The mitogenome presented here will contribute to the examination of genetic differentiation for E. vermiculata and understanding of the mitochondrial DNA evolution in Eremias. PMID- 26153741 TI - Phylogenetic position of Scombropidae within teleostei: the complete mitochondrial genome of the gnomefish, Scombrops gilberti. AB - The complete mitochondrial genome of the Japanese gnomefish, Scombrops gilberti, was determined using a PCR-based method. The total length of mitochondrial DNA (mtDNA) is 16 518 bp, which includes 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one control region. The mitochondrial gene arrangement of S. gilberti was found to be identical to that of other scombropid and indeed, other teleosts as well. Maximum likelihood analysis revealed that Scombropidae forms a sister group to Pempheriformes. PMID- 26153742 TI - Complete mitochondrial genome of Parachromis managuensis (Perciformes: Cichlidae). AB - The complete mitochondrial genome of Parachromis managuensis (Perciformes: Cichlidae) is sequenced in this study. The genome sequence was 16 526 bp in length, with the base composition of 28.1% A, 25.5% T, 15.4% G, 31.0% C. The gene order and genes are the same as found in other previously reported cichlid fish, including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 1 D-loop region. Except for ND6 gene and eight tRNA genes, all other mitochondrial genes were encoded on the heavy strand. Parachromis managuensis was closely related to Amphilophus citrinellus and Petenia splendid, based on its complete mitochondrial genome sequences. This complete mitogenome data provide the basis for taxonomic and conservation research of Parachromis managuensis. PMID- 26153743 TI - The complete chloroplast genome sequence of Fatsia japonica (Apiales: Araliaceae) and the phylogenetic analysis. AB - In this study, we have sequenced the complete chloroplast genome of Fatsia japonica, a well-known ornamental and potential medicinal plant. The complete chloroplast genome of F. japonica is 155 613 bp in length with 62.09% AT content, has a typical quadripartite structure with large (LSC 86 487 bp) and small (SSC 17 866 bp) single-copy regions separated by a pair of inverted repeats (IRs 25 929 bp) and contains 114 unique genes with 18 genes duplicated in the IR making a total of 132 genes. The phylogenetic analysis indicated the position of F. japonica in Apiales and has the potential to facilitate a better understanding of the intergeneric relationships in the family. PMID- 26153744 TI - Complete mitogenomes of Spotbreast angelfish (Genicanthus melanospilos) and Blackstriped angelfish (Genicanthus lamarck) (Teleostei: Pomacanthidae). AB - In this study, we used the next-generation sequencing method to deduce two complete mitogenomes of Spotbreast angelfish (Genicanthus melanospilos) and Blackstriped angelfish (Genicanthus lamarck) for the first time. The assembled mitogenome, consisting of 16 736 bp and 16 616 bp, showing 91.8% identity each other. Both mitogenome follow the typical vertebrate arrangement, including 13 protein coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes and a non-coding control region of D-loop. D-loop contains 1026 bp in G. melanospilos and 912 bp in G. lamarck and locates between tRNA-Pro and tRNA-Phe. The overall GC content is 46.2% for G. melanospilos and 46.3% for G. lamarck. Complete mitogenomes of G. melanospilos and G. lamarck provide essential and important DNA molecular data for phylogenetic and evolutionary analysis for marine angelfishes. PMID- 26153745 TI - Characterization of the mitochondrial genome of Amolops tuberodepressus (Anura: Ranidae). AB - Amolops tuberodepressus is a vulnerable torrent frog, and only know distributed in the Wuliang Mountain in southwestern China. In the present study, the mitochondrial DNA (mtDNA) sequence of A. tuberodepressus was determined. The genome was 18 348 bp in length, and it contained 37 genes (13 protein-coding genes, two ribosomal RNAs, and 22 transfer RNAs), one partial control region and one light strand replication origin. The gene rearrangement was observed within the WANCY tRNA gene cluster region, which similar to other Amolops species. In this paper, we utilized 13 protein-coding genes of A. tuberodepressus and other 10 closely ranid species to construct the species phylogenetic tree to verify the A. tuberodepressus was accuracy. PMID- 26153746 TI - The complete chloroplast genome sequence of Dendropanax morbifera (Leveille). AB - The complete chloroplast genome sequence of Dendropanax morbifera, an economically and medicinally important endemic tree species in Korea, was obtained by de novo assembly with whole-genome sequence data and manual correction. A circular 156 366-bp chloroplast genome showed typical chloroplast genome structure comprising a large single copy region of 86 475 bp, a small single copy region of 18 125 bp, and a pair of inverted repeats of 25 883 bp. The chloroplast genome harbored 87 protein-coding genes. Phylogenetic analysis with the chloroplast genome revealed that D. morbifera is most closely related to Dendropanax dentiger, an evergreen tree species in China and Southeastern Asia. PMID- 26153747 TI - Complete mitochondrial genome of the Onychostruthus taczanowskii (Aves, Passeridae) and its phylogenetic analysis. AB - The complete mitochondrial genome sequence of Onychostruthus taczanowskii consisted 16 917 bp, the genome harbored the same gene order with that of other birds, contained 13 protein-coding genes, 22 tRNAs, 2 rRNAs and 1 non-coding control region. The all tRNAs formed typical cloverleaf secondary structures, except tRNA(Ser (AGN)) and tRNA(Phe). The control region was located between tRNA(Glu) and tRNA(Phe) with 1310 bp in length, which consist of three domains: highly variable domain I, central conserved domain II and conserved sequence domain III. According to the phylogenetic analysis, Onychostruthus taczanowskii had a closer relationship with Pyrgilauda ruficollis, and Passer montanus were sister to them. PMID- 26153748 TI - Ion torrent next-generation sequencing reveals the complete mitochondrial genome of endangered mahseer Tor khudree (Sykes, 1839). AB - The complete mitochondrial genome of an endangered mahseer (Deccan mahseer), Tor khudree was sequenced using Ion torrent platform for the first time. The genome sequence was 16 573 bp in size, and consists of 13 protein coding genes, 22 tRNAs, 2 rRNA genes and 1 control region. The gene organization and its order were similar to other vertebrates. The overall base composition was A: 31.9%, G: 15.6%, C: 27.68%, T: 24.76%, A + T content 56.6% and the G + C content 43.32%. The phylogenetic tree constructed using a maximum likelihood model showed sister relationship between T. khudree and Tor tambroides. PMID- 26153749 TI - The complete chloroplast genome sequence of Dieffenbachia seguine (Araceae). AB - The nucleotide sequence of the chloroplast genome from Dieffenbachia seguine is the first to have complete genome sequence from genus of Dieffenbachia family Araceae. The genome size is 163 699 bp in length, with 36.4% GC content. A pair of inverted repeats (IRs, 25 235 bp) is separated by a large single copy region (LSC, 90 780 bp) and a small single copy region (SSC, 22 449 bp). The chloroplast genome contains 113 unique genes, 88 protein-coding genes, 37 tRNA genes, and four rRNA genes. In these genes, 16 genes contained single intron and two genes composed of double introns. A maximum likelihood phylogenetic analysis using complete chloroplast genome revealed that Dieffenbachia seguine belongs to the Araceae family of the Arecidae group, which is conform to the traditional classification. PMID- 26153750 TI - The complete mitochondrial genome of the Hexagrammos otakii (Scorpaeniformes: Hexagrammidae). AB - The complete mitochondrial genome of the Hexagrammos otakii has been sequenced. The mitochondrial genome is 16 513 bp in length, containing 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one control region. The gene order and composition of H. otakii mitochondrial genome was similar to that of most other vertebrates. The overall nucleotides base composition of the heavy strand is A (26.90%), G (17.33%), C (29.87%), and T (25.90%). With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. The 22 tRNA genes could be folded into a typical clover-leaf secondary structure. Seen from the phylogenetic tree, H. otakii, Hexagrammos agrammus and Hexagrammos lagocephalus from the same genus clustered into one branch. PMID- 26153751 TI - The complete chloroplast genome sequence of the medicinal plant Rheum palmatum L. (Polygonaceae). AB - The complete chloroplast genome of the medicinal plant Rheum palmatum L. (Polygonaceae) has been reconstructed from the whole-genome Illumina sequencing data. The genome is 161 541 bp in length, and exhibits a typical quadripartite structure of the large (LSC, 86 518 bp) and small (SSC, 13 111 bp) single-copy regions, separated by a pair of inverted repeats (IRs, 30 956 bp each). The chloroplast genome contains 131 genes, including 84 protein-coding genes (78 PCG species), eight ribosomal RNA genes (four rRNA species) and 37 transfer RNA genes (28 tRNA species). Phylogenetic tree based on the maximum parsimony (MP) analysis of 65 chloroplast protein-coding genes for 13 taxa demonstrated a close relationship between R. palmatum and Fagopyrum esculentum subsp. ancestrale in Polygonaceae. PMID- 26153752 TI - Sequencing of complete mitochondrial genome of brown algal Saccharina sp. ye-W. AB - The complete sequence (37 657 bp) of the mitochondrial DNA (mtDNA) of the Saccharina sp. ye-W was determined using Illumina sequencing data. The genome contains 38 protein-coding genes (PCG), three ribosomal RNA (rRNA), 25 transfer RNA (tRNA) genes that are typical of Saccharina mtDNA. Phylogenetic analysis based on the mitochondrial genomes of brown algae indicated that Saccharina sp. ye-W and Saccharina longissima, Saccharina japonica are the most closely related species, which strongly supports their close phylogenetic affinity. PMID- 26153753 TI - Complete mitochondrial genome of Cygnus cygnus (Aves, Anseriformes, Anatidae). AB - In this study, the complete mitochondrial genome of Cygnus cygnus (Aves, Anseriformes, Anatidae) was sequenced. The genome, consisting of 16 724 base pairs (bp), encoded 13 protein coding genes (PCGs), two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and a control region (CR). Two rRNA genes for 12S rRNA (991 bases) and 16S rRNA (1608 bases) are located between tRNA-Phe and tRNA-Leu (UUR) and divided by the tRNA-Val. The CR, of 1156 bp in length, is located between tRNA-Glu and tRNA-Phe. The overall base composition of C. cygnus is G + C: 47.2%, A + T: 52.8%, apparently with a slight AT bias. Phylogenetic analysis showed that the C. cygnus was closed to Cygnus columbianus. PMID- 26153754 TI - Complete sequence and characterization of mitochondrial genome in the swimming crab Portunus sanguinolentus (Herbst, 1783) (Decapoda, Brachyura, Portunidae). AB - The three-spot swimming crab Portunus sanguinolentus (Herbst, 1783) is a commercially important fishery species, widely distributed in the Indo-Pacific region. In this study, we present the complete mitochondrial genome of P. sanguinolentus. The genome is 16 027 bp in length with circular organization, encoding the standard set of 13 protein-coding genes, 22 tRNA genes, and two rRNA genes. The overall A + T content is 65.60%, which is lower than that of its congeneric species Portunus pelagicus and Portunus trituberculatus. The mitogenome carries 1254 bp of intergenic region constituting 7.82% of the genome, and six pairs of overlapping genes with the overlap size from 1 to 7 bp. The complete mitogenome sequence information of P. sanguinolentus would provide useful data for further studies on population genetics and molecular systematics. PMID- 26153755 TI - The investigation of genetic diversity and evolution of Daweishan Mini chicken based on the complete mitochondrial (mt)DNA D-loop region sequence. AB - This study evaluated the genetic diversity and origin of Daweishan Mini chickens using mtDNA sequence polymorphism. Blood samples from 30 Daweishan Mini chickens were collected. The complete D-loop was PCR amplified, sequenced and compared with the DNA data of five Red Junglefowl (Gallus gallus) subspecies. Eighteen variable sites that defined six haplotypes were observed. The six haplotypes were clustered into four clades (A, B, D and E), of which clade A and B were dominant. Clades Aand B were clustered with G.g. spadiceus, indicating these two clades may have originated from this subspecies. These results show there is diversity in the middle of the mtDNA D-loop, and indicate there are multiple maternal origins for Daweishan Mini chickens. It appears that G.g. spadiceus contributed more to the evolution of the Daweishan Mini chickens breed than the other four subspecies tested here. PMID- 26153756 TI - Cervical Chondrocutaneous Branchial Remnants. AB - OBJECTIVE: Cervical chondrocutaneous branchial remnants are rare malformations usually found in the lower neck. As high as 76% of patients have been reported to have associated anomalies. We review the literature and report a case series of seven patients with cervical cartilaginous remnants. DESIGN: A retrospective case series of seven patients identified from the electronic hospital records. RESULTS: Seven patients with cervical chondrocutaneous branchial remnants were identified (six boys and one girl). Only one of the patients had associated anomalies. CONCLUSIONS: A review of the literature revealed no evidence for sinuses or cysts related to cervical chondrocutaneous branchial remnants. Operative treatment can be postponed to a suitable and safe age. There is marked variation in the reported prevalence of associated anomalies, ranging from 11% to 76%. PMID- 26153757 TI - Effectiveness of Tongue-lip Adhesion for Obstructive Sleep Apnea in Infants With Robin Sequence Measured by Polysomnography. AB - OBJECTIVE: Tongue-lip adhesion (TLA) is commonly used to relieve obstructive sleep apnea (OSA) in infants with Robin sequence (RS), but few studies have evaluated its efficacy with objective measures. The purpose of this study was to measure TLA outcomes using polysomnography. Our hypothesis was that TLA relieves OSA in most infants. METHODS: This is a retrospective study of infants with RS who underwent TLA from 2011 to 2014 and had at least a postoperative polysomnogram. Predictor variables included demographic and birth characteristics, surgeon, syndromic diagnosis, GILLS score, preoperative OSA severity, and clinical course. A successful outcome was defined as minimal OSA (apnea-hypopnea index score < 5) on postoperative polysomnogram and no need for additional airway intervention. Descriptive, bivariate, and regression statistics were computed, and statistical significance was set at P < .05. RESULTS: Eighteen subjects who had TLA at a mean age of 28 +/- 4.7 days were included. Thirteen (72.2%) had a confirmed or suspected syndrome, and the mean GILLS score was 3 +/- 0.3. All parameters trended toward improvement from the preoperative to postoperative polysomnograms, and improvement in OSA severity, oxygen saturation nadir, and arousals per hour was statistically significant (P < .02). This effect was significant across categories of surgeon, syndrome, and GILLS score. Nine subjects (50%) met the criteria for a successful outcome. Bivariate and regression analyses did not demonstrate a significant relationship between success and any predictor variable. CONCLUSIONS: TLA improved airway obstruction in all infants with RS but resolved OSA in only nine patients, and success was unpredictable. PMID- 26153758 TI - Oral Health-Related Quality of Life in Children in Chile Treated for Cleft Lip and Palate: A Case-Control Approach. AB - OBJECTIVE: To compare the oral health-related quality of life of patients treated for cleft lip and/or cleft palate (CL/P) versus unaffected children between 8 and 15 years of age using a Spanish-language version of the Child Oral Health Impact Profile (COHIP-Sp) administered to a Chilean population. DESIGN: A cross sectional study with a matched case-control design was used. METHODS: Participants were 48 children (mean age 11.3 years) with a history of CL/P from three cities in Chile and one group of 96 children (mean age 11.2 years) unaffected by CL/P. The COHIP-Sp was applied to both groups. Quality of life was compared according to the overall score and the average score of items and domains on the COHIP-Sp scale between the two groups (Mann-Whitney U test; P < .05). RESULTS: The COHIP-Sp score was 94.1 +/- 19.3 in children with CL/P and 97.1 +/- 15.6 for the control group (P = .31). A significantly lower score was observed in the group with CL/P in the domains "functional well-being" (P = .001) and "school environment" (P = .001); the only average in favor of the quality of life in children with CL/P was in "self-image" (P = .0002). CONCLUSION: The oral health-related quality of life of children with a history of CL/P was similar to that of the control group. Nevertheless, a lower quality of life was observed concerning items associated with speech and being understood by other people. Further study into the risk factors associated with surgery and rehabilitative treatment is recommended. PMID- 26153759 TI - Ear Infection in Isolated Cleft Lip: Etiological Implications. AB - BACKGROUND AND HYPOTHESIS: Chronic ear infections are a common occurrence in children with orofacial clefts involving the secondary palate. Less is known about the middle ear status of individuals with isolated clefts of the lip, although several studies have reported elevated rates of ear infection in this group. The purpose of this retrospective study was to test the hypothesis that chronic ear infections occur more frequently in isolated cleft lip cases (n = 94) compared with controls (n = 183). METHODS: A questionnaire was used to obtain information on history of chronic ear infection. The association between ear infection status (present/absent) and cleft lip status (cleft lip case/control) was tested using both chi-square and logistic regression. RESULTS AND CONCLUSIONS: The reported occurrence of chronic ear infection was significantly greater in cleft lip cases (31%) compared with unaffected controls (11%). After adjusting for age and sex, having a cleft lip increased the odds of being positive for ear infection by a factor greater than 3 (odds ratio = 3.698; 95% confidence interval = 1.91 to 7.14). Within cleft lip cases, there was no difference in the occurrence of ear infection by defect laterality or by the type of clefting present in the family history. Although velopharyngeal insufficiency was present in 18.4% of our cleft lip sample, there was no statistical association between ear infection and abnormal speech patterns. These results may have potential implications both for the clinical management of isolated cleft lip cases and for understanding the etiology of orofacial clefting. PMID- 26153760 TI - Corrigendum: An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction. PMID- 26153761 TI - Arsenic-containing hydrocarbons and arsenic-containing fatty acids: Transfer across and presystemic metabolism in the Caco-2 intestinal barrier model. AB - SCOPE: Arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) represent two classes of arsenolipids occurring naturally in marine food. Toxicological data are yet scarce and an assessment regarding the risk to human health has not been possible. Here, we investigated the transfer and presystemic metabolism of five arsenolipids in an intestinal barrier model. METHODS AND RESULTS: Three AsHCs and two AsFAs were applied to the Caco-2 intestinal barrier model. Thereby, the short-chain AsHCs reached up to 50% permeability. Transport is likely to occur via passive diffusion. The AsFAs showed lower intestinal bioavailability, but respective permeabilities were still two to five times higher as compared to arsenobetaine or arsenosugars. Interestingly, AsFAs were effectively biotransformed while passing the in vitro intestinal barrier, whereas AsHCs were transported to the blood-facing compartment essentially unchanged. CONCLUSION: AsFAs can be presystemically metabolised and the amount of transferred arsenic is lower than that for AsHCs. In contrast, AsHCs are likely to be highly intestinally bioavailable to humans. Since AsHCs exert strong toxicity in vitro and in vivo, toxicity studies with experimental animals as well as a human exposure assessment are needed to assess the risk to human health related to the presence of AsHCs in seafood. PMID- 26153762 TI - Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease. AB - A hallmark of celiac disease is autoantibodies to transglutaminase 2 (TG2). By visualizing TG2-specific antibodies by antigen staining of affected gut tissue, we identified TG2-specific plasma cells in the lamina propria as well as antibodies in the subepithelial layer, inside the epithelium, and at the brush border. The frequency of TG2-specific plasma cells were found not to correlate with serum antibody titers, suggesting that antibody production at other sites may contribute to serum antibody levels. Upon commencement of a gluten-free diet, the frequency of TG2-specific plasma cells in the lesion dropped dramatically within 6 months, yet some cells remained. The frequency of TG2-specific plasma cells in the celiac lesion is thus dynamically regulated in response to gluten exposure. Laser microdissection of plasma cell patches, followed by antibody gene sequencing, demonstrated that clonal cells were seeded in distinct areas of the mucosa. This was confirmed by immunoglobulin heavy chain repertoire analysis of plasma cells isolated from individual biopsies of two untreated patients, both for TG2-specific and non-TG2-specific cells. Our results shed new light on the processes underlying the B-cell response in celiac disease, and the approach of staining for antigen-specific antibodies should be applicable to other antibody mediated diseases. PMID- 26153763 TI - Donor interleukin-22 and host type I interferon signaling pathway participate in intestinal graft-versus-host disease via STAT1 activation and CXCL10. AB - Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation, limiting the success of this therapy. We previously reported that interleukin-22 (IL-22) participates to aGVHD development, but the underlying mechanisms of its contribution remain poorly understood. In this study, we analyzed the mechanism of the pathological function of IL-22 in intestinal aGVHD. Ex-vivo colon culture experiments indicated that IL 22 was able to induce Th1-like inflammation via signal transducer and activator of transcription factor-1 (STAT1) and CXCL10 induction in the presence of type I interferon (IFN). To evaluate a potential synergy between IL-22 and type I IFN in aGVHD, we transplanted recipient mice, either wild-type (WT) or type I IFN receptor deficient (IFNAR(-/-)), with bone marrow cells and WT or IL-22 deficient (IL-22(-/-)) T cells. We observed a decreased GVHD severity in IFNAR(-/-) recipient of IL-22(-/-) T cells, which was associated with a lower level of STAT1 activation and reduced CXCL10 expression in the large intestine. Finally, immunohistochemistry staining of STAT1 performed on gastrointestinal biopsies of 20 transplanted patients showed exacerbated STAT1 activation in gastrointestinal tissues of patients with aGVHD as compared with those without aGVHD. Thus, interfering with both IL-22 and type I IFN signaling may provide a novel approach to limit aGVHD. PMID- 26153765 TI - A proposal for a special section in the International Journal of Psychology: Youth and the Great Recession - are values, achievement orientation and health affected? PMID- 26153764 TI - A protective role for IL-13 receptor alpha 1 in bleomycin-induced pulmonary injury and repair. AB - Molecular mechanisms that regulate lung repair vs. progressive scarring in pulmonary fibrosis remain elusive. Interleukin (IL)-4 and IL-13 are pro-fibrotic cytokines that share common receptor chains including IL-13 receptor (R) alpha1 and are key pharmacological targets in fibrotic diseases. However, the roles of IL-13Ralpha1 in mediating lung injury/repair are unclear. We report dysregulated levels of IL-13 receptors in the lungs of bleomycin-treated mice and to some extent in idiopathic pulmonary fibrosis patients. Transcriptional profiling demonstrated an epithelial cell-associated gene signature that was homeostatically dependent on IL-13Ralpha1 expression. IL-13Ralpha1 regulated a striking array of genes in the lung following bleomycin administration and Il13ra1 deficiency resulted in exacerbated bleomycin-induced disease. Increased pathology in bleomycin-treated Il13ra1(-/-) mice was due to IL-13Ralpha1 expression in structural and hematopoietic cells but not due to increased responsiveness to IL-17, IL-4, IL-13, increased IL-13Ralpha2 or type 1 IL-4R signaling. These data highlight underappreciated protective roles for IL 13Ralpha1 in lung injury and homeostasis. PMID- 26153767 TI - A Time Difference Method for Measurement of Phase Shift between Distributed Feedback Laser Diode (DFB-LD) Output Wavelength and Intensity. AB - A time difference method to conveniently measure the phase shift between output wavelength and intensity of distributed feedback laser diodes (DFB-LDs) was proposed. This approach takes advantage of asymmetric absorption positions at the same wavelength during wavelength increase and decrease tuning processes in the intensity-time curve by current modulation. For its practical implementation, a measurement example of phase shift was demonstrated by measuring a time difference between the first time and the second time attendances of the same gas absorption line in the intensity-time curve during one sine or triangle modulation circle. The phase shifts at modulation frequencies ranging from 50 Hz to 50 kHz were measured with a resolution of 0.001pi. As the modulation frequency increased the shift value increased with a slowed growth rate. PMID- 26153768 TI - Modular Energy-Efficient and Robust Paradigms for a Disaster-Recovery Process over Wireless Sensor Networks. AB - Robust paradigms are a necessity, particularly for emerging wireless sensor network (WSN) applications. The lack of robust and efficient paradigms causes a reduction in the provision of quality of service (QoS) and additional energy consumption. In this paper, we introduce modular energy-efficient and robust paradigms that involve two archetypes: (1) the operational medium access control (O-MAC) hybrid protocol and (2) the pheromone termite (PT) model. The O-MAC protocol controls overhearing and congestion and increases the throughput, reduces the latency and extends the network lifetime. O-MAC uses an optimized data frame format that reduces the channel access time and provides faster data delivery over the medium. Furthermore, O-MAC uses a novel randomization function that avoids channel collisions. The PT model provides robust routing for single and multiple links and includes two new significant features: (1) determining the packet generation rate to avoid congestion and (2) pheromone sensitivity to determine the link capacity prior to sending the packets on each link. The state of-the-art research in this work is based on improving both the QoS and energy efficiency. To determine the strength of O-MAC with the PT model; we have generated and simulated a disaster recovery scenario using a network simulator (ns-3.10) that monitors the activities of disaster recovery staff; hospital staff and disaster victims brought into the hospital. Moreover; the proposed paradigm can be used for general purpose applications. Finally; the QoS metrics of the O MAC and PT paradigms are evaluated and compared with other known hybrid protocols involving the MAC and routing features. The simulation results indicate that O MAC with PT produced better outcomes. PMID- 26153766 TI - A novel crosstalk between TLR4- and NOD2-mediated signaling in the regulation of intestinal inflammation. AB - Although Toll-like receptor 4 (TLR4)- and nucleotide-binding oligomerization domain 2 (NOD2)-mediated signaling mechanisms have been extensively studied individually, the crosstalk between them in the regulation of intestinal mucosal defense and tissue homeostasis has been underappreciated. Here, we uncover some novel activities of NOD2 by gene expression profiling revealing the global nature of the cross-regulation between TLR4- and NOD2-mediated signaling. Specifically, NOD2 is able to sense the intensity of TLR4-mediated signaling, resulting in either synergistic stimulation of Interluekin-12 (IL-12) production when the TLR signaling intensity is low; or in the inhibition of IL-12 synthesis and maintenance of intestinal mucosal homeostasis when the TLR signaling intensifies. This balancing act is mediated through receptor-interacting serine/threonine kinase 2, and the transcriptional regulator CCAAT/enhancer-binding protein alpha (C/EBPalpha) via its serine 248 phosphorylation by Protein Kinase C. Mice deficient in C/EBPalpha in the hematopoietic compartment are highly susceptible to chemically induced experimental colitis in an IL-12-dependent manner. Additionally, in contrast to the dogma, we find that the major Crohn's disease associated NOD2 mutations could cause a primarily immunodeficient phenotype by selectively impairing TLR4-mediated IL-12 production and host defense. To restore the impaired homeostasis would be a way forward to developing novel therapeutic strategies for inflammatory bowel diseases. PMID- 26153769 TI - Inertial Sensing Based Assessment Methods to Quantify the Effectiveness of Post Stroke Rehabilitation. AB - In clinical settings, traditional stroke rehabilitation evaluation methods are subjectively scored by occupational therapists, and the assessment results vary individually. To address this issue, this study aims to develop a stroke rehabilitation assessment system by using inertial measurement units. The inertial signals from the upper extremities were acquired, from which three quantitative indicators were extracted to reflect rehabilitation performance during stroke patients' movement examination, i.e., shoulder flexion. Both healthy adults and stroke patients were recruited to correlate the proposed quantitative evaluation indices and traditional rehab assessment scales. Especially, as a unique feature of the study the weight for each of three evaluation indicators was estimated by the least squares method. The quantitative results demonstrate the proposed method accurately reflects patients' recovery from pre-rehabilitation, and confirm the feasibility of applying inertial signals to evaluate rehab performance through feature extraction. The implemented assessment scheme appears to have the potential to overcome some shortcomings of traditional assessment methods and indicates rehab performance correctly. PMID- 26153770 TI - User Expectations for Media Sharing Practices in Open Display Networks. AB - Open Display Networks have the potential to allow many content creators to publish their media to an open-ended set of screen displays. However, this raises the issue of how to match that content to the right displays. In this study, we aim to understand how the perceived utility of particular media sharing scenarios is affected by three independent variables, more specifically: (a) the locativeness of the content being shared; (b) how personal that content is and (c) the scope in which it is being shared. To assess these effects, we composed a set of 24 media sharing scenarios embedded with different treatments of our three independent variables. We then asked 100 participants to express their perception of the relevance of those scenarios. The results suggest a clear preference for scenarios where content is both local and directly related to the person that is publishing it. This is in stark contrast to the types of content that are commonly found in public displays, and confirms the opportunity that open displays networks may represent a new media for self-expression. This novel understanding may inform the design of new publication paradigms that will enable people to share media across the display networks. PMID- 26153771 TI - Bearing Fault Diagnosis Based on Statistical Locally Linear Embedding. AB - Fault diagnosis is essentially a kind of pattern recognition. The measured signal samples usually distribute on nonlinear low-dimensional manifolds embedded in the high-dimensional signal space, so how to implement feature extraction, dimensionality reduction and improve recognition performance is a crucial task. In this paper a novel machinery fault diagnosis approach based on a statistical locally linear embedding (S-LLE) algorithm which is an extension of LLE by exploiting the fault class label information is proposed. The fault diagnosis approach first extracts the intrinsic manifold features from the high-dimensional feature vectors which are obtained from vibration signals that feature extraction by time-domain, frequency-domain and empirical mode decomposition (EMD), and then translates the complex mode space into a salient low-dimensional feature space by the manifold learning algorithm S-LLE, which outperforms other feature reduction methods such as PCA, LDA and LLE. Finally in the feature reduction space pattern classification and fault diagnosis by classifier are carried out easily and rapidly. Rolling bearing fault signals are used to validate the proposed fault diagnosis approach. The results indicate that the proposed approach obviously improves the classification performance of fault pattern recognition and outperforms the other traditional approaches. PMID- 26153772 TI - A Meliorated Multi-Frequency Band Pyroelectric Sensor. AB - This article proposes a meliorated multi-frequency band pyroelectric sensor for detecting subjects with various velocities, namely extending the sensing frequency under good performance from electrical signals. A tactic, gradually increasing thickness of the ZnO layers, is used for redeeming drawbacks of a thicker pyroelectric layer with a tardy response at a high-frequency band and a thinner pyroelectric layer with low voltage responsivity at a low-frequency band. The proposed sensor is built on a silicon substrate with a thermal isolation layer of a silicon nitride film, consisting of four pyroelectric layers with various thicknesses deposited by a sputtering or aerosol deposition (AD) method and top and bottom electrodes. The thinnest ZnO layer is deposited by sputtering, with a low thermal capacity and a rapid response shoulders a high-frequency sensing task, while the thicker ZnO layers are deposited by AD with a large thermal capacity and a tardy response shoulders a low-frequency sensing task. The fabricated device is effective in the range of 1 KHz~10 KHz with a rapid response and high voltage responsivity, while the ZnO layers with thicknesses of about 0.8 MUm, 6 MUm, 10 MUm and 16 MUm are used for fabricating the meliorated multi frequency band pyroelectric sensor. The proposed sensor is successfully designed, analyzed, and fabricated in the present study, and can indeed extend the sensing range of the multi-frequency band. PMID- 26153773 TI - Curved Microneedle Array-Based sEMG Electrode for Robust Long-Term Measurements and High Selectivity. AB - Surface electromyography is widely used in many fields to infer human intention. However, conventional electrodes are not appropriate for long-term measurements and are easily influenced by the environment, so the range of applications of sEMG is limited. In this paper, we propose a flexible band-integrated, curved microneedle array electrode for robust long-term measurements, high selectivity, and easy applicability. Signal quality, in terms of long-term usability and sensitivity to perspiration, was investigated. Its motion-discriminating performance was also evaluated. The results show that the proposed electrode is robust to perspiration and can maintain a high-quality measuring ability for over 8 h. The proposed electrode also has high selectivity for motion compared with a commercial wet electrode and dry electrode. PMID- 26153775 TI - A Smart City Lighting Case Study on an OpenStack-Powered Infrastructure. AB - The adoption of embedded systems, mobile devices and other smart devices keeps rising globally, and the scope of their involvement broadens, for instance, in smart city-like scenarios. In light of this, a pressing need emerges to tame such complexity and reuse as much tooling as possible without resorting to vertical ad hoc solutions, while at the same time taking into account valid options with regard to infrastructure management and other more advanced functionalities. Existing solutions mainly focus on core mechanisms and do not allow one to scale by leveraging infrastructure or adapt to a variety of scenarios, especially if actuators are involved in the loop. A new, more flexible, cloud-based approach, able to provide device-focused workflows, is required. In this sense, a widely used and competitive framework for infrastructure as a service, such as OpenStack, with its breadth in terms of feature coverage and expanded scope, looks to fit the bill, replacing current application-specific approaches with an innovative application-agnostic one. This work thus describes the rationale, efforts and results so far achieved for an integration of IoT paradigms and resource ecosystems with such a kind of cloud-oriented device-centric environment, by focusing on a smart city scenario, namely a park smart lighting example, and featuring data collection, data visualization, event detection and coordinated reaction, as example use cases of such integration. PMID- 26153776 TI - Evaluation of a Cubature Kalman Filtering-Based Phase Unwrapping Method for Differential Interferograms with High Noise in Coal Mining Areas. AB - Differential interferometric synthetic aperture radar has been shown to be effective for monitoring subsidence in coal mining areas. Phase unwrapping can have a dramatic influence on the monitoring result. In this paper, a filtering based phase unwrapping algorithm in combination with path-following is introduced to unwrap differential interferograms with high noise in mining areas. It can perform simultaneous noise filtering and phase unwrapping so that the pre filtering steps can be omitted, thus usually retaining more details and improving the detectable deformation. For the method, the nonlinear measurement model of phase unwrapping is processed using a simplified Cubature Kalman filtering, which is an effective and efficient tool used in many nonlinear fields. Three case studies are designed to evaluate the performance of the method. In Case 1, two tests are designed to evaluate the performance of the method under different factors including the number of multi-looks and path-guiding indexes. The result demonstrates that the unwrapped results are sensitive to the number of multi looks and that the Fisher Distance is the most suitable path-guiding index for our study. Two case studies are then designed to evaluate the feasibility of the proposed phase unwrapping method based on Cubature Kalman filtering. The results indicate that, compared with the popular Minimum Cost Flow method, the Cubature Kalman filtering-based phase unwrapping can achieve promising results without pre filtering and is an appropriate method for coal mining areas with high noise. PMID- 26153777 TI - Unique double recurrence of cerebral arteriovenous malformation. AB - Surgically treated patients with arteriovenous malformations (AVMs) are considered cured when the postoperative angiogram proves complete resection. However, despite no residual nidus or early draining vein on postoperative angiogram, rare instances of AVM recurrence have been reported in adults. In this paper, the authors present a case of a 24-year-old woman with asymptomatic double recurrence of her cerebral AVM after angiographically proven complete resection. To the authors' knowledge, this patient represents the first case with double de novo asymptomatic recurrence of Spetzler-Martin grade I AVM. Also, she represents the first case with unique AVM criteria in each recurrence. PMID- 26153778 TI - Anterior thalamic nucleus deep brain Stimulation (DBS) for drug-resistant complex partial seizures (CPS) with or without generalization: long-term evaluation and predictive outcome. AB - BACKGROUND: Drug-resistant epileptic patients account for 40 % of cases of epilepsy. Consequently, specific therapeutic options could be surgical resection or, if not indicated, deep brain stimulation (DBS). The aim of this study is to review data from patients affected by drug-resistant complex partial epilepsy with or without generalization treated by anterior thalamic nucleus (AN) DBS to evaluate the efficacy and potential future applications of this approach as a standard method for palliative seizure control. METHODS: Six patients affected by drug-resistant complex partial seizures underwent AN DBS from March 2007 to February 2011. The preoperative tests consisted of electroencephalography (EEG), video EEG, morphologic and functional magnetic resonance imaging (MRI), non-acute positron emission tomography (PET), neuropsychological evaluation, Liverpool seizure scale, and Quality Of Life In Epilepsy (QOLIE). These tests and a seizure diary were also administered during a follow-up of at least 3 years. RESULTS: The improvement in terms of decrease of seizures was more than 50 % in patients affected by complex partial seizures strictly related to limbic system origin. The amelioration was unsatisfactory for patients having anatomical lesions outside the limbic structures with evidence of late diffusion in limbic areas. One patient died 40 days after surgery for reasons not concerned with DBS. CONCLUSIONS: Although the limited number of enrolled patients limits the reliability of data, the results are in accordance with those found in the recent literature and deserve to be considered for further studies regarding real efficacy, indications, stimulation parameters, side effects, and complications. PMID- 26153774 TI - Nucleic Acid Aptamers: An Emerging Tool for Biotechnology and Biomedical Sensing. AB - Detection of small molecules or proteins of living cells provides an exceptional opportunity to study genetic variations and functions, cellular behaviors, and various diseases including cancer and microbial infections. Our aim in this review is to give an overview of selected research activities related to nucleic acid-based aptamer techniques that have been reported in the past two decades. Limitations of aptamers and possible approaches to overcome these limitations are also discussed. PMID- 26153779 TI - Lung cancer among coal miners, ore miners and quarrymen: smoking-adjusted risk estimates from the synergy pooled analysis of case-control studies. AB - OBJECTIVES: Working in mines and quarries has been associated with an elevated lung cancer risk but with inconsistent results for coal miners. This study aimed to estimate the smoking-adjusted lung cancer risk among coal miners and compare the risk pattern with lung cancer risks among ore miners and quarrymen. METHODS: We estimated lung cancer risks of coal and ore miners and quarrymen among 14 251 lung cancer cases and 17 267 controls from the SYNERGY pooled case-control study, controlling for smoking and employment in other at-risk occupations. RESULTS: Ever working as miner or quarryman (690 cases, 436 controls) was associated with an elevated odds ratio (OR) of 1.55 [95% confidence interval (95% CI) 1.34-1.79] for lung cancer. Ore miners (53 cases, 24 controls) had a higher OR (2.34, 95% CI 1.36-4.03) than quarrymen (67 cases, 39 controls; OR 1.92, 95% CI 1.21-3.05) and coal miners (442 cases, 297 controls; OR 1.40, 95% CI 1.18-1.67), but CI overlapped. We did not observe trends by duration of exposure or time since last exposure. CONCLUSIONS: This pooled analysis of population-based studies demonstrated an excess lung cancer risk among miners and quarrymen that remained increased after adjustment for detailed smoking history and working in other at risk occupations. The increase in risk among coal miners were less pronounced than for ore miners or quarrymen. PMID- 26153780 TI - Preoperative state anxiety, acute postoperative pain, and analgesic use in persons undergoing lower limb amputation. AB - OBJECTIVES: The current study examined the relationship between preoperative anxiety and acute postoperative phantom limb pain (PLP), residual limb pain (RLP), and analgesic medication use in a sample of persons undergoing lower limb amputation. MATERIALS AND METHODS: Participants included 69 adults admitted to a large level 1 trauma hospital for lower limb amputation. Participants' average pain and anxiety during the previous week were assessed before amputation surgery. RLP, PLP, and analgesic medication use were measured on each of the 5 days following amputation surgery. RESULTS: Results of partial-order correlations indicated that greater preoperative anxiety was significantly associated with greater ratings of average PLP for each of the 5 days following amputation surgery, after controlling for preoperative pain ratings and daily postoperative analgesic medication use. Partial correlation values ranged from 0.30 to 0.62, indicating medium to large effects. Preoperative anxiety was also significantly associated with ratings of average RLP only on postoperative day 1, after controlling for preoperative pain ratings and daily postoperative analgesic medication use (r=0.34, P<0.05). Correlations between preoperative anxiety and daily postoperative analgesic medication dose became nonsignificant when controlling for preamputation and postamputation pain ratings. DISCUSSION: These findings suggest that anxiety may be a risk factor for acute postamputation PLP and RLP, and indicate that further research to examine these associations is warranted. If replicated, the findings would support research to examine the extent to which modifying preoperative anxiety yields a reduction in postoperative acute PLP and RLP. PMID- 26153781 TI - Patients with neck pain are less likely to improve if they experience poor sleep quality: a prospective study in routine practice. AB - OBJECTIVE: To assess whether sleep quality (SQ) at baseline is associated with improvement in pain and disability at 3 months. MATERIALS AND METHODS: Four hundred twenty-two subacute and chronic patients with neck pain (NP) were recruited in 32 physiotherapy, primary care, and specialized centers. NP, referred pain, disability, catastrophizing, depression, and SQ were assessed through validated questionnaires, upon recruitment and 3 months later. Correlations between baseline scores were calculated through the Spearman coefficient. Improvements in NP, disability, and SQ were defined as a reduction of >=30% of baseline score. Six estimative logistic regression models were developed to assess the association between baseline SQ and improvement of NP, baseline SQ and improvement of disability, baseline NP and improvement of SQ, baseline disability and improvement of SQ, the evolutions of NP and SQ, and the evolutions of disability and SQ. RESULTS: Most patients were subacute and mildly impaired. Regression models showed that better SQ at baseline was associated with improvement of NP (odds ratio=0.91 [95% confidence interval, 0.83-0.99]), but not disability (1.04 [0.95-1.13]); the improvement of SQ was associated with more severe NP at baseline (1.26 [1.07-1.49)], but not with baseline disability (0.99 [0.97-1.02]); and that improvement in SQ was associated with improvements in NP (3.48 [1.68-7.20]), and disability (5.02 [2.39-10.11]). DISCUSSION: NP is less likely to improve in patients with poorer SQ, irrespective of age, sex, catastrophizing, depression, or treatments prescribed for NP. Future studies should confirm these results with more severely impaired patients. PMID- 26153783 TI - Cognitive load in distributed and massed practice in virtual reality mastoidectomy simulation. AB - OBJECTIVES/HYPOTHESIS: Cognitive load theory states that working memory is limited. This has implications for learning and suggests that reducing cognitive load (CL) could promote learning and skills acquisition. This study aims to explore the effect of repeated practice and simulator-integrated tutoring on CL in virtual reality (VR) mastoidectomy simulation. STUDY DESIGN: Prospective trial. METHODS: Forty novice medical students performed 12 repeated virtual mastoidectomy procedures in the Visible Ear Simulator: 21 completed distributed practice with practice blocks spaced in time and 19 participants completed massed practice (all practices performed in 1 day). Participants were randomized for tutoring with the simulator-integrated tutor function. Cognitive load was estimated by measuring reaction time in a secondary task. Data were analyzed using linear mixed models for repeated measurements. RESULTS: The mean reaction time increased by 37% during the procedure compared with baseline, demonstrating that the procedure placed substantial cognitive demands. Repeated practice significantly lowered CL in the distributed practice group but not in massed practice group. In addition, CL was found to be further increased by 10.3% in the later and more complex stages of the procedure. The simulator-integrated tutor function did not have an impact on CL. CONCLUSION: Distributed practice decreased CL in repeated VR mastoidectomy training more consistently than was seen in massed practice. This suggests a possible effect of skills and memory consolidation occurring over time. To optimize technical skills learning, training should be organized as time-distributed practice rather than as a massed block of practice, which is common in skills-training courses. LEVEL OF EVIDENCE: N/A. PMID- 26153784 TI - Response on Pneumococcal Vaccine in Preterm Infants After Neutral and Acidic Oligosaccharides Supplementation. AB - BACKGROUND: Supplementation of oligosaccharides in premature infants was shown to influence the immune system. We determined the effect of combined short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and pectin-derived acidic oligosaccharides (pAOS) on antibody concentrations after pneumococcal conjugate vaccination in very preterm infants. METHODS: Very preterm infants with gestational age <32 weeks and/or birth weight <1500 g were randomized to receive enteral supplementation with scGOS/lcFOS/pAOS or placebo between days 3 and 30 of life. Blood samples were collected at birth, 5 and 12 months of age and compared with term samples from a Dutch cross-sectional population-based serosurveillance study. IgG antibody levels to pneumococcal capsular polysaccharides were determined by multiplex immunoassay. RESULTS: In total, 113 preterm infants were included with similar baseline and nutritional characteristics in both groups. After 3 primary pneumococcal vaccinations, the scGOS/lcFOS/pAOS-group had lower GMC antibody concentrations (ug/mL; serotype 4: 1.53, 6B:0.25, 9V: 1.19, 14: 2.39, 18C: 1.88, 19F: 7.42, 23F: 0.72) than the placebo group (serotype 4: 3.29, 6B: 0.79, 9V:2.64, 14: 4.52, 18C: 3.13, 19F: 14.64, 23F: 1.88; all P < 0.05), but comparable with those in the term control group (serotype 4: 0.97, 6B: 0.32, 9V: 1.67, 14: 3.24, 18C: 2.03, 19F: 5.06, 23F: 0.59; all P > 0.05). After the booster vaccination at 11 months, antibody levels were no longer different between the two preterm groups. CONCLUSION: Enteral supplementation of scGOS/lcFOS/pAOS has a regulatory effect on the response to conjugated polysaccharide pneumococcal vaccine with normalization of the enhanced responses in preterm infants toward levels similar to healthy term infants. PMID- 26153782 TI - P-glycoprotein is expressed and causes resistance to chemotherapy in EBV-positive T-cell lymphoproliferative diseases. AB - Epstein-Barr virus-positive T-cell lymphoproliferative diseases (EBV-T-LPDs) are rare lymphomas with poor prognosis. Although chemotherapeutic strategies such as CHOP have been often selected, they have exhibited only limited efficacy. To clarify the mechanism of chemoresistance, we examined P-glycoprotein (P-gp) expression. P-gp acts as an energy-dependent efflux pump that excretes drugs from the cytoplasm, resulting in low-intracellular drug concentrations and poor sensitivity to chemotherapy. We examined P-gp expression in EBV-positive cells by immunohistochemistry staining in three patients of EBV-T-LPDs and the expression was detected in all patients. We also examined mdr1 mRNA expression by reverse transcriptase polymerase-chain reaction (RT-PCR) in EBV-positive tumor cells from these patients and additional three patients. The expression was detected in all examined patients. In five EBV-T-LPDs patients, P-gp function was detected by Rhodamine-123 efflux assay in these cells. The efflux was inhibited by treatment with a P-gp inhibitor, cyclosporine A (CsA). We also examined and detected P-gp expression in EBV-positive T-cell lines SNT8 and SNT16 established from EBV-T LPDs patients, by RT-PCR and western blotting. The function was also detected by Rhodamine-123 efflux in these cell lines. Inhibition and knock down of P-gp by CsA and siRNA, respectively, enhanced etoposide- and doxorubicin-induced cell death in the EBV-positive T-cell lines. Finally, we infected the T-cell line MOLT4 with EBV, and found that mdr1 mRNA expression and Rhodamine 123 efflux were upregulated after infection. These results indicated that enhanced P-gp expression contributed to the chemoresistance of EBV-T-LPDs. PMID- 26153785 TI - Progress on Many Fronts. PMID- 26153786 TI - Compassionate Care for Patients With Complex Regional Pain Syndrome. AB - Complex regional pain syndrome (CRPS) is a debilitating condition characterized by specific symptoms such as intense pain and loss of function. This syndrome can be so devastating that it affects quality of life. Often, CRPS is misdiagnosed and misunderstood, which can be extremely frustrating for patients. The purpose of the survey in this study was to query actual patients living with CRPS to gain additional knowledge and suggestions to help improve their care. Respondents expressed a variety of emotions when asked about their healthcare experiences, which suggests that healthcare providers need to be better educated about CRPS so they can provide more compassionate care for patients trying to cope with this condition. PMID- 26153787 TI - Psychosocial Challenges Experienced by Partners of People With Parkinson Disease. AB - Although researchers have examined issues related to partners providing care for a person with Parkinson disease (PWP), few have explored partners' broader psychosocial experiences. To investigate this underexplored area, individual, in depth interviews with 23 partners of PWPs were conducted. Participants reported significant psychosocial challenges, including having the PWP withdraw from communication, being unable to "rescue" the PWP, being the recipient of the PWP's frustration, expressing impatience with the PWP, shouldering increased responsibility, being confronted with possibly losing the PWP, losing valued activities, feeling housebound, being unable to predict the PWP's daily well being, and experiencing uncertainty about future caregiving and disease progression. These results indicate that being the partner of a PWP involves serious, complex psychosocial challenges related to both caregiving and noncaregiving issues. This research highlights the need for a family-centered approach to Parkinson care and provides valuable insight that can inform interventions and nursing practice for this population. PMID- 26153788 TI - The Treatment of Migraine Headache in the Presence of Selective Serotonin Reuptake Inhibitor Use: Pharmacokinetic Considerations. PMID- 26153789 TI - Feasibility of a Home-Based Speed of Processing Training Program in Middle-Aged and Older Adults With HIV. AB - There has been much optimism over the positive impact of combination antiretroviral therapy (cART) on life expectancy for people with HIV; however, those aging with HIV fear potential day-to-day challenges associated with the development of cognitive deficits. The presence of cognitive deficits has generated major safety concerns because it has been shown to impact driving, mobility, and employment. Given the efficacy of a computerized speed of processing training program administered in the laboratory to older adults and adults with HIV, this study was designed to determine the feasibility of using a home-based speed of processing training program to improve cognitive function in middle-aged and older adults with HIV. In this within-subject pre-post experimental design, 20 middle-aged and older adults (i.e., age of 40+ years) with HIV were administered a brief neuropsychological assessment to gauge their baseline cognitive function before participating in a 10-hour home-based computerized cognitive remediation training program. In addition to self-reported cognitive gains, a 6-week posttest indicated significant improvements on the Useful Field of View, a measure of speed of processing and possible transfer to the Timed Instrumental Activities of Daily Living test, a measure of everyday functioning. These findings show that speed of processing training can successfully improve cognitive function in this vulnerable population even when administered in remote settings such as the privacy of one's home. PMID- 26153791 TI - Temporal Profiles of Cerebral Perfusion Pressure After Subarachnoid Hemorrhage. AB - INTRODUCTION: Insufficient cerebral perfusion pressure (CPP) after aneurysmal subarachnoid hemorrhage can impair cerebral blood flow. We examined the temporal profiles of CPP change and tested whether these profiles were associated with delayed cerebral ischemia (DCI). METHOD: CPP values were retrospectively reviewed for 238 subjects. Intracranial pressure and mean arterial pressure values were obtained every 2 hours for 14 days. Induced hypertension was utilized to prevent vasospasm. The linear and quadratic CPP changes over time were tested using growth curve analysis. Multivariable logistic regression was utilized to examine the association between DCI and percentages of CPP values of >110, >100, <70, and <60 mm Hg. DCI was defined as neurological deterioration because of impaired cerebral blood flow. RESULTS: Between-subject differences accounted for 39% of variation in CPP values. There was a significant linear increase in CPP values over time (beta = 0.06, SE = 0.006, p < .001). The covariance (-0.52, SE = 0.09, p < .001) between initial CPP and linear parameter was negative, indicating that subjects with high CPP on admission had a slower rate of increase whereas those with low CPP had a faster rate of increase. For every 10% increase in the proportion of CPP of >100 or >110 mm Hg, the odds of DCI increased by 1.21 and 1.43, respectively (p < .05). CONCLUSIONS: The longer the time patients spent with high CPP, the greater the odds for DCI. When used prophylactically, induced hypertension contributes to higher CPP values. On the basis of the CPP trends and correlations observed, induced hypertension may not confer expected benefits in patients with aneurysmal subarachnoid hemorrhage. PMID- 26153792 TI - Factors associated with depression in older carers. AB - OBJECTIVE: Depression is an adverse outcome frequently seen in carers. With the increasing ageing population and reliance on informal carers, this study aims to identify factors associated with depression in carers in the older age group, using factors that have not been previously investigated. METHODS: We conducted a cross-sectional analysis of 202 older carers using the Geriatric Depression scale, demographics, personality traits, attitudes to ageing and other carer characteristics. RESULTS: Increased hours spent caring and higher levels of neuroticism were all factors associated with depression. The care-recipient diagnosis, other personality traits, attitudes to ageing, leisure-physical activity (PA) and domestic-PA were not significantly associated with depression. CONCLUSIONS: These findings have important implications for interventions to target at-risk carers. PMID- 26153793 TI - FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance. AB - FGF21 is a key metabolic regulator modulating physiological processes and its pharmacological administration improves metabolic profile in preclinical species and humans. We used native-FGF21 and a long-acting FGF21 (PF-05231023), to determine the contribution of liver and brown adipose tissue (BAT) towards metabolic improvements in Zucker rats and DIO mice (DIOs). FGF21 improved glucose tolerance and liver insulin sensitivity in Zuckers without affecting BW and improved liver function by decreased lipogenesis, increased fatty acid oxidation and improved insulin signaling. Through detailed lipidomic analyses of liver metabolites in DIOs, we demonstrate that FGF21 favorably alters liver metabolism. We observed a dose-dependent increase of [(18)F]-FDG-glucose uptake in interscapular BAT (iBAT) of DIOs upon FGF21 administration. Upon excision of iBAT (X-BAT) and administration of FGF21 to mice housed at 80 degrees F or 72 degrees F, the favorable effects of FGF21 on BW and glucose excursion were fully retained in both sham and X-BAT animals. Taken together, we demonstrate the liver as an organ that integrates the actions of FGF21 and provide metabolic benefits of FGF21 in Zucker rats and DIOs. Finally, our data demonstrates iBAT does not play a role in mediating favorable metabolic effects of FGF21 administration in DIOs housed at 80 degrees F or 72 degrees F. PMID- 26153794 TI - PSMA expression is highly homogenous in primary prostate cancer. AB - BACKGROUND: Prostate-specific membrane antigen (PSMA) is a suggested target for antibody-based therapy of prostate cancer, potentially involved in the regulation of cell migration. As heterogeneity may limit the applicability of targeted therapies, this study was undertaken to estimate the degree of heterogeneity of PSMA expression in prostate cancer. METHODS: For heterogeneity analysis, a prostate cancer heterogeneity TMA containing samples from 10 different tumor blocks of 189 consecutive prostate cancers was used. PSMA expression was analyzed by immunohistochemistry. RESULTS: PSMA expression was found in 97.6% of 1171 interpretable tissue spots including 260 (22.2%) with weak, 345 (29.5%) with moderate, and 538 (45.9%) with strong positivity. On a patient level, a positive PSMA immunostaining was found in 172 of 173 analyzable patients (99.4%) with at least a weak staining reaction. PSMA immunostaining was homogenously positive in 161 prostate cancers (93.6%), whereas heterogenous PSMA positivity was seen in 11 of 172 positive cases (6.4%). In these cases, heterogeneity was intrafocal in 8 cases (72.7%) and interfocal in 27.3% cases. PSMA expression was completely absent in 1 patient. CONCLUSIONS: Given the high frequency and high homogeneity of PSMA expression in prostate cancer, we conclude that increased PSMA expression may occur early in prostate cancer development. High homogeneity of PSMA expression is a strong argument for a high utility of PSMA as a prostate cancer drug target. PMID- 26153795 TI - Role of Organics in Regulating ClNO2 Production at the Air-Sea Interface. AB - We report measurements of the product yield for nitryl chloride (ClNO2) production following the reactive uptake of dinitrogen pentoxide (N2O5) to a wide variety of ambient seawater samples as well as seawater mimics. The ClNO2 yield, as measured for ambient seawater collected from both coastal and open ocean waters, was found to be both insensitive to chlorophyll-a, a marker for biological activity, and significantly lower (0.16-0.30) than that expected for equivalent salt-containing solutions (0.82 +/- 0.05). Suppression in the ClNO2 yield can be induced by the addition of aromatic organic compounds (e.g., phenol and humic acid) to synthetic seawater matrices. In the case of phenol, surface tension measurements reveal that the surface phenol:chloride ratio can be enhanced by more than a factor of 100 as compared to bulk ratios for subtle changes in surface tension (<1.5 mN m(-1)), providing a mechanism to suppress ClNO2 production at low bulk phenol concentrations. We interpret measurements of the dependence of the ClNO2 yield on phenol using a kinetic model, where we confine the surface enhancement in phenol to the top 1 nm of the interface. Our results are most consistent with a model where N2O5 is ionized within the first three water monolayers (<1 nm), where the product nitronium ions react rapidly with interfacial phenol molecules. These results suggest that ClNO2 may not be formed at the air-sea interface at the yield expected for NaCl, and that the reactive uptake of N2O5 and the subsequent product yield of ClNO2 may serve as a unique probe for the composition of the interfacial region of the sea surface microlayer. PMID- 26153798 TI - PEDOT as a Flexible Organic Electrode for a Thin Film Acoustic Energy Harvester. AB - An efficient thin film acoustic energy harvester was explored using flexible poly(3,4-ethylene dioxythiophene) (PEDOT) films as electrodes in an all-organic triboelectric generator (AO-TEG). A thin film AO-TEG structured as PEDOT/Kapton//PET/PEDOT was prepared by the solution casting polymerization(SCP) on the dielectric polymer films. As-prepared AO-TEG showed high flexibility and durability due to the strong adhesion between the electrodes and the dielectric polymer. The short-circuit current density (Jsc), open-circuit voltage (Voc), and maximum power density (Pw) reached 50 mA/m(2), 700 V, and 12.9 W/m(2) respectively. The output current density decreased with the increase in the electrode resistance (Re), but the energy loss in the organic electrodes was negligible. The AO-TEG could light up 180 LEDs instantaneously upon touching of the AO-TEG with a palm (~120 N). With the flexible structure, the AO-TEG was worn as clothes and generated electricity to light LEDs upon regular human movement. Furthermore, the AO-TEG was applicable as a thin film acoustic energy harvester, which used music to generate electricity enough for powering of 5 LEDs. An AO-TEG with a PEDOT electrode (Re = 200 Omega) showed instantaneous peak-to-peak voltage generation of 11 V under a sound pressure level (SPL) of 90-100 dB. The harvested acoustic energy through the AO-TEG was 350 MUJ from the 4 min playing of the same single song. This is the first demonstration of a flexible triboelectric generator (TEG) using an organic electrode for harvesting acoustic energy from ambient environment. PMID- 26153796 TI - Collaborative Enhancement of Endothelial Targeting of Nanocarriers by Modulating Platelet-Endothelial Cell Adhesion Molecule-1/CD31 Epitope Engagement. AB - Nanocarriers (NCs) coated with antibodies (Abs) to extracellular epitopes of the transmembrane glycoprotein PECAM (platelet endothelial cell adhesion molecule 1/CD31) enable targeted drug delivery to vascular endothelial cells. Recent studies revealed that paired Abs directed to adjacent, yet distinct epitopes of PECAM stimulate each other's binding to endothelial cells in vitro and in vivo ("collaborative enhancement"). This phenomenon improves targeting of therapeutic fusion proteins, yet its potential role in targeting multivalent NCs has not been addressed. Herein, we studied the effects of Ab-mediated collaborative enhancement on multivalent NC spheres coated with PECAM Abs (Ab/NC, ~180 nm diameter). We found that PECAM Abs do mutually enhance endothelial cell binding of Ab/NC coated by paired, but not "self" Ab. In vitro, collaborative enhancement of endothelial binding of Ab/NC by paired Abs is modulated by Ab/NC avidity, epitope selection, and flow. Cell fixation, but not blocking of endocytosis, obliterated collaborative enhancement of Ab/NC binding, indicating that the effect is mediated by molecular reorganization of PECAM molecules in the endothelial plasmalemma. The collaborative enhancement of Ab/NC binding was affirmed in vivo. Intravascular injection of paired Abs enhanced targeting of Ab/NC to pulmonary vasculature in mice by an order of magnitude. This stimulatory effect greatly exceeded enhancement of Ab targeting by paired Abs, indicating that '"collaborative enhancement"' effect is even more pronounced for relatively large multivalent carriers versus free Abs, likely due to more profound consequences of positive alteration of epitope accessibility. This phenomenon provides a potential paradigm for optimizing the endothelial-targeted nanocarrier delivery of therapeutic agents. PMID- 26153799 TI - Photochemically grown silver nanodecahedra with precise tuning of plasmonic resonance. AB - The ability to control the local surface plasmonic resonance (LSPR) absorption peaks of silver nanoparticles will greatly broaden the scope of their practical application. Conventional methods tune the LSPR peaks by modifying the shape or size of the silver nanoparticles. Here, we present a novel method to tune the LSPR band by controlling the particle corner sharpness. A modified photochemical method was used to prepare silver nanoparticles. It was found that the nanoparticles irradiated using light-emitting diodes (LEDs) with a wavelength of 455 nm were decahedral, although the reaction temperature was different. However, the in-plane dipole LSPR peak of the as-prepared silver nanodecahedra exhibited an evident red shift from 460 nm to 500 nm during the synthesis process, and the wavelength of the LSPR peak increased linearly as the reaction time increased. A numerical simulation conducted to investigate the mechanism behind the shift revealed that the red shift of the LSPR peak was mainly induced by the evolution of the corner sharpness of the silver nanodecahedra. These results demonstrated the effectiveness of the method in precisely tuning the LSPR peak by controlling the reaction time. By turning off the irradiation light, the photochemical process could be immediately terminated, and the LSPR peak of the silver nanoparticles remained constant. Compared with conventional methods, the present tuning precision can reach 1 nm. PMID- 26153797 TI - Cultured Cells from the Human Oocyte Cumulus Niche Are Efficient Feeders to Propagate Pluripotent Stem Cells. AB - Pluripotency is at the crossroads of stem cell research and biology of reproduction. The mature metaphase II oocyte contains the key factors for pluripotency induction and maintenance as assessed by its capacity to reprogram somatic nuclei. The cumulus cells (CCs) niche that surrounds the oocyte is crucial for its maturation and presumably for the oocyte to acquire its competence to confer pluripotency. In this study, we examined whether cells cultured from the human mature metaphase II oocyte CC niche (hCC) could be used as feeders for the propagation of human induced pluripotent stem cells. The induced pluripotent (iPS) cells cultured on hCC (hCC-iPS) were assessed for their pluripotency potential by their expression of pluripotency-associated genes such as Oct4, Nanog, and TRA1-60 and their competence to differentiate into the three germ layers in vitro (embryoid bodies) as well as in vivo (teratoma formation). We show that not only the hCC-iPS cells maintained their pluripotency potential, but they also exhibited much better self-renewal performance in terms of proliferation rate compared to the same cells cultured on human foreskin fibroblast (hFF) feeders (hFF-iPS). A comparative gene expression profile study of hCC and hFF revealed significant differences (P < 0.05) in expression of cellular matrix components and an upregulation in hCC of genes known to be important players in cell proliferation such as interleukin 6 gene (IL6). PMID- 26153800 TI - Reducing zirconium(IV) phthalocyanines and the structure of a Pc(4-)Zr complex. AB - The synthesis and characterization of the ring-unsubstituted zirconium phthalocyanine PcZrCl2 (; Pc(x-) = phthalocyaninato(x-)) and its reduction products are described. X-ray analysis of (crystallized from hot 1 chloronaphthalene) reveals that is a chloride-bridged dimer [PcZrCl]2(MU-Cl)2 in the solid-state; was also characterized by UV-vis/MCD spectroscopy and cyclic voltammetry, which indicated reduction potentials at -0.55, -0.95 and -1.28 V. Although attempts to access these Pc-ring reduced species with KC8 led to mixtures of reduced products due to the insolubility of both starting materials, one equivalent of the reducing agent KEt3BH reacted with to generate Pc(3-) containing species, as indicated by visible Q-band spectral changes (from lambdamax = 686 for to 589/611 nm), a single ESR peak (g = 2.001) and paramagnetically shifted (1)H NMR resonances consistent with the presence of a Pc radical anion. Addition of two equivalents of KEt3BH to generated Pc(4-) containing species, confirmed by a shift in lambdamax to 522 nm and upfield shifted (1)H NMR peaks relative to . Reaction of with one and two equivalents of LiCp* did not generate Cp*-substituted products but also effected reduction to analogous Pc(3-) and Pc(4-) species. This latter material, the air-sensitive ring di-reduced "ate"-complex Pc(4-)Zr(LiCl)1.5(DME)3, of the form [LiCl(DME)4]0.5[Pc(4-)ZrClLi(DME)] was structurally characterized, illustrating partial bond localization in the Pc(4-) ring, which also adopts a saddle-shape vs. the more typical dome-configuration found in . This represents a rare example of an isolated and structurally characterized Pc(4-) complex. PMID- 26153801 TI - Electroclinic effect in a chiral carbosilane-terminated 5-phenylpyrimidine liquid crystal with 'de Vries-like' properties. AB - The chiral carbosilane-terminated liquid crystal 2-[(2S,3S)-2,3-difluorohexyloxy] 5-[4-(12,12,14,14,16,16-hexamethyl-12,14,16 trisilaheptadecyloxy)phenyl]pyrimidine () undergoes a smectic A*-smectic C* phase transition with a maximum layer contraction of only 0.2%. It exhibits an electroclinic effect (ECE) comparable to that reported for the 'de Vries-like' liquid crystal and shows no appreciable optical stripe defects due to horizontal chevron formation. PMID- 26153802 TI - HIV self-testing kits. PMID- 26153803 TI - PSA tests and cancer: keeping men fully informed. PMID- 26153804 TI - Ebola revisited: lessons in managing global epidemics. AB - The latest statistics for the number of new cases of Ebola virus disease (EVD) in West Africa point to the near containment of the virus. While the current threat will not be deemed over until 42 days after the last case to be diagnosed has twice tested negative, there is now a shift in focus from an emphasis on containment to that of policy review and capacity building in light of lessons learned. This article primarily focuses on Sierra Leone. It revisits the issues surrounding the epidemic, seeking to summarise both the negative and positive aspects of the response at local and global levels, as well as highlights fresh perspectives from healthcare workers in the field for the management of similar epidemics. PMID- 26153805 TI - Aseptic practice recommendations for circulating operating theatre nurses. AB - Aseptic practices prevent exposure of a surgical wound to microbes, operating theatre environment and personnel. The circulating nurse assists the operating theatre personnel and supervises aseptic practices preventing surgical site infections. In the absence of analytical tools, few studies exist on intraoperative nursing-related aseptic practices. This study introduces recommendations to assess the role of the circulating nurse in aseptic practices. The authors used international recommendations and research findings to construct a 20-item self-report instrument with a demonstrated reliability across the scale. The authors structured the scale based on three phases: establishment; maintenance; and disestablishment of a sterile operating field. The tool was tested among operating theatre and day surgery nurses, and compared the differences in the mean acceptance rates of aseptic practice recommendations based on background characteristics. College-level nurses and nurses with 15 or more years' work experience accepted the recommendations at higher levels than bachelor-level nurses and nurses with less work experience. Continual assessment of the evidence base and comprehensive evaluation represent important components in further developing the tool. A reasonable number of items covering clinical practice are necessary for assessing the effectiveness and cost-effectiveness of aseptic practices, and a larger response rate is needed to validate the tool in future. PMID- 26153806 TI - What I would have told my first-year self. PMID- 26153807 TI - Venous thromboembolism: use of graduated compression stockings. AB - This article aims to review the use of graduated compression stockings in the prevention of venous thromboembolism (VTE). This is particularly important owing to the increasing number of people who die from hospital-acquired VTE and deep vein thrombosis. In addition, there is the need to raise awareness among nurses and other health professionals on the overall impact of VTE, and the number of patients with a range of conditions including cancer who may be at risk of developing VTE. Graduated compression stockings, when used alone, have been found to be effective in preventing VTE in a number of patients in hospital and community settings. However, there is evidence that when used together with other preventative measures such as pharmacological prophylaxis are more effective than graduated compression stockings alone. It is also important that the correct size of graduated compression stocking is used and how they are applied as these may have a significant impact on VTE. The role of the nurse in thromboprophylaxis and implications for practice are discussed. PMID- 26153808 TI - Older people with dysphagia: transitioning to texture-modified food. AB - Older people with dysphagia are at high risk of malnutrition. To maintain safe oral and nutritional intake, solid food may be texture-modified. Little is known about the transition experiences of older people who move from normal to texture modified foods. The aim of this study was to describe residents' experiences as they transitioned from normal food to texture-modified food. The study used a qualitative descriptive design and individual interviews were conducted with a study group of 28 participants (residents, family members, nursing and care staff, and speech and language therapists). The interviews were thematically analysed. The findings suggest that transition creates the risk of distress, reducing eating to a matter of necessity and hunger, and that the process is perceived as abrupt, and characterised by lack of communication and awareness of the need for change. A key finding is that the language used during transition can be adversely affected by the management of risk. This language promotes a culture of care that emphasises the limitations of residents, reduces their motivation to eat and hinders the delivery of person-centred care. The findings suggest that care facilities for older people need to revisit their dysphagia management protocols to ensure that they support a person-centred approach for recipients of texture-modified food. PMID- 26153809 TI - Indian ICU nurses' perceptions of and attitudes towards organ donation. AB - Nurses play a significant role in identifying and securing potential organ donors in the clinical environment. Research among Indian nurses related to organ donation is sparse. The present study aimed to investigate nurses' attitudes towards organ donation. A cross-sectional descriptive survey was carried out among nurses (n=184) at a tertiary care centre. Data were collected through self report questionnaire. A majority (81%) of the respondents were 'willing to sign the card' for organ donation; however, only 3.8% (n=7) of them actually 'signed the organ donation card'. There were significant associations found between intentions to sign the organ donation card and gender (x2=5.852; p<0.054), religion (x2=40.175; p<0.000), and experience caring for brain-dead patients (x2=22.790; p<0.001). The researchers strongly suggest continuing education for nurses to enhance skills and knowledge, as well as sensitivity to cultural, ethical, social, and religious issues, and advocacy in the area of organ donation. Furthermore, nurse administrators must take the initiative to develop guidelines clarifying the role of nurses in the organ donation and transplantation process to promote organ donation and improve rates. PMID- 26153810 TI - How critical care nurses' roles and education affect organ donation. AB - Organ and tissue dysfunction and failure cause high mortality rates around the world. Tissue and organs transplantation is an established, cost-effective, life saving treatment for patients with organ failure. However, there is a large gap between the need for and the supply of donor organs. Acute and critical care nurses have a central role in the organ donation process, from identifying and assessing potential donors and supporting their families to involvement in logistics. Nurses with an in-depth knowledge of donation understand its clinical and technical aspects as well as the moral and legal considerations. Nurses have a major role to play in tackling organ and tissue shortages. Such a role cannot be adequately performed if nurses are not fully educated about donation and transplant. Such education could be incorporated into mandatory training and completed by all nurses. PMID- 26153811 TI - The importance of communication in sustaining hope at the end of life. AB - How can health professionals, especially those working in busy environments, foster hope and communicate effectively and therapeutically with patients at the end of their lives? Many authors agree that failure to comprehend the essence of what patients are communicating, either verbally or non-verbally, can adversely affect the level of support that health professionals can offer, and risks increasing patients' suffering and isolation, leaving them feeling hopeless. Anxiety and fear frequently invoke hopelessness and often cause patients to reject advice and important information given by clinicians. This article focuses on the importance of therapeutic communication in sustaining hope for patients at the end of life. PMID- 26153812 TI - Can the NHS become a 7-day service for all? PMID- 26153813 TI - Safeguarding vulnerable adults. AB - Nurses have a professional duty to safeguard vulnerable adults from abuse under the provisions of the Nursing and Midwifery Council's (NMC) revised Code (2015). With adult abuse continuing to increase, all members of the nursing team are well placed to identify and take action to safeguard the vulnerable. This article sets out how the Care Act 2014 seeks to improve the safeguarding of vulnerable adults and the role of nurses in that process. PMID- 26153814 TI - The urgent need to improve care for people with mental ill health. PMID- 26153815 TI - Relationships: from staff nurse to nurse consultant. Part 9: patients' visitors. PMID- 26153816 TI - Nursing in China: how does it compare with the UK? PMID- 26153817 TI - Prevalence and risk factors associated with colonization and infection of extensively drug-resistant Pseudomonas aeruginosa: a systematic review. AB - Pseudomonas aeruginosa is a Gram-negative human pathogen with extensively drug resistant (XDR) strains emerging in hospitals across the globe. This systematic review is focused on the worldwide prevalence of XDR P. aeruginosa (XDR-PA) and on the risk factors associated with its colonization and infection, based on literature available through PubMed, Web of Science and BioMed Central databases. An overview of surveillance systems is provided as well as a synopsis on the prevalence of XDR-PA, showing an increase in recent reports. Risk factors independently associated with XDR-PA colonization or infections are described in four groups with reference to antimicrobial therapy, medical devices as well as patient- and hospital environment-related factors. PMID- 26153819 TI - Multicomponent domino reactions of hydrazinecarbodithioates: concise access to 3 substituted 5-thiol-1,3,4-thiadiazolines. AB - Two classes of addition/cycloaddition cascade reactions of hydrazinecarbodithioate (1) have been developed under mild reaction conditions. Reaction of hydrazinecarbodithioate (1) with formaldehyde solution (2) and propiolic acid (3) gives 3-propargyl-5-thiol-2,3-dihydro-1,3,4-thiadiazoles (5) via a decarboxylative coupling/cycloaddition domino sequence. When propiolic acid (3) is switched to phenyl boronic acid (4), a petasis/cycloaddition domino reaction is instead observed, in which 3-benzyl-5-thiol-2,3-dihydro-1,3,4 thiadiazoles (6) are obtained. Both these reactions show a wide range of functional-group compatibility for propiolic acids and aryl boronic acids, and give the corresponding products in moderate to good yields. PMID- 26153821 TI - Impaired pulmonary function is a risk predictor for sudden cardiac death in men. AB - OBJECTIVES: Little is known about the association of reduced pulmonary function and the risk of sudden cardiac death (SCD). Our aim was to examine the relation of forced expiratory volume (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC with SCD in a population-based sample of men. METHODS: This study was based on 1250 men 42-60 years of age without chronic obstructive pulmonary disease, asthma, and lung cancer. During the 20-year follow-up, 95 SCDs occurred. FEV1, FVC, and ratio of FEV1 to FVC were used as lung function tests. RESULTS: As a continuous variable, each 10% increase in the percentage predicted FEV1 was associated with 18% (adjusted risk 0.82, 95% CI 0.73-0.93, P < 0.002) reduced risk for SCD. Subjects with most reduced (lowest quintile) FEV1 had a 3.5-fold increased risk for SCD (95% CI 1.42-8.41, P = 0.006), after adjustment for conventional risk factors. Similar results were observed with FVC. The results remained statistically significant among non-smokers and smokers respectively. CONCLUSION: Our study shows that reduced lung function is a robust predictor of SCD in middle-aged men. Lung function test may be useful in risk stratification for SCD in general population. PMID- 26153822 TI - Pulsatility index in combination with biomarkers or mean arterial pressure for the prediction of pre-eclampsia: Systematic literature review and meta-analysis. AB - INTRODUCTION: Our objective was to perform a meta-analysis examining the sensitivity of pulsatility index (PI) and various biomarkers and PI and mean arterial pressure (MAP) for the prediction of pre-eclampsia. MATERIAL AND METHODS: PubMed, CENTRAL, and Embase databases were searched from inception until 8 May 2014 using combinations of the search terms: pre-eclampsia, ultrasonography, pregnancy, biomarker, mean arterial pressure, placental protein 13, pregnancy-associated plasma protein-A, placental growth factor, activin A, inhibin A, pulsatility index. The pooled sensitivity of PI + biomarkers and PI + MAP were calculated, and reported with corresponding 95% confidence intervals (CIs). RESULTS: Fifteen studies were included in the meta-analysis. The pooled sensitivity of all biomarkers for the prediction of pre-eclampsia was 0.669 (95% CI 0.610-0.723), for the prediction of early-onset pre-eclampsia was 0.830 (95% CI 0.794-0.861), and for the prediction of late-onset pre-eclampsia was 0.564 (95% CI 0.499-0.627). Similarly, the predictive ability of PI + MAP for early onset pre-eclampsia was good (sensitivity 0.894), while that for late-onset was poor (sensitivity 0.570). CONCLUSION: The combination of PI and different biomarkers or MAP exhibits a good predictive ability for early-onset pre eclampsia, and poor predictive ability for late-onset pre-eclampsia. PMID- 26153823 TI - Proprotein convertase subtilisin-kexin type 9 as a biomarker for the severity of coronary artery disease. AB - AIM: To evaluate the relation of proprotein convertase subtilisin-kexin type 9 (PCSK9) levels to coronary artery disease (CAD). METHODS: A total of 1031 consecutive individuals (552 CAD and 479 controls) were prospectively enrolled. The associations of plasma PCSK9 levels with the incidence and severity of CAD were investigated. Further, mediator analysis was performed to detect the potential mechanisms of the associations. RESULTS: No difference in PCSK9 levels between CAD patients and controls was detected (median 224.75 versus 224.64 ng/mL, P > 0.05). However, the CAD group had higher PCSK9 levels than the control group when adjusting for the confounding factors (228.03 +/- 1.01 versus 219.28 +/- 1.02 ng/mL, P = 0.019). PCSK9 levels were also associated with the severity of CAD assessed by the Gensini score (GS) system (P for trend < 0.05). Logistic regression analysis showed that PCSK9 levels were associated with an increased CAD risk (OR 3.296 and 5.130 for the incidence and severity, respectively). Importantly, mediator analysis indicated that the effects of PCSK9 levels on CAD were mediated by lipid (around 20%) and inflammation (around 15%). CONCLUSIONS: PCSK9 levels were positively associated with the severity of CAD; the relatively important mechanisms including lipid and inflammation pathways were partly involved in this association. PMID- 26153824 TI - Design and structure of the Estonian HIV Cohort Study (E-HIV). AB - BACKGROUND: Estonia is experiencing the new Eastern Europe human immunodeficiency virus (HIV) epidemic, with the highest incidence of new infections in the EU. We describe demographic changes, HIV-related laboratory parameters and co-infections during the concentrated HIV epidemic using the Estonian HIV Cohort Study (E-HIV) database, founded in 2009. METHODS: All 3750 subjects in the E-HIV database on December 31, 2013 were included. Subjects were divided into risk groups: people who inject drugs (PWIDs), sexual transmission (heterosexual/homosexual), and other (perinatal) or unknown risk group. Subjects diagnosed before 2009 (first period) and after (second period) were analyzed separately. RESULTS: The mean age at diagnosis has increased from 22.8 years (interquartile range (IQR) = 19.5 27.2) to 29.7 years (IQR = 25.3-36.2) (p < 0.001) between the first and second periods. PWIDs were younger than other transmission groups (23.2 vs 27.1; p < 0.001). There is a statistical difference in the route of transmission among genders, with overall increasing sexual transmission. The most common AIDS defining illness was tuberculosis (0.5%). HIV/hepatitis C (HCV) co-infection was diagnosed in 42% of cases. The population median CD4 + cell count at diagnosis has declined over the years; in total 53% have been late presenters. Half of the patients are receiving antiretroviral treatment (cART). The most common combinations are nucleoside reverse transcriptase inhibitor (NRTI) backbone plus protease inhibitors (PIs) (57%) or NRTI backbone + non-NRTIs (42%). CONCLUSION: The E-HIV enables us to fill the gap in the lack of data on the course of the new Eastern European HIV epidemic. These data demonstrate that the HIV epidemic in Estonia is moving from PWIDs to the general population, suggesting that prevention measures and testing guidelines should be revised. PMID- 26153825 TI - Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis. PMID- 26153829 TI - Differential Electrochemical Mass Spectrometer Cell Design for Online Quantification of Products Produced during Electrochemical Reduction of CO2. AB - The discovery of electrocatalysts that can efficiently reduce CO2 to fuels with high selectivity is a subject of contemporary interest. Currently, the available analytical methods for characterizing the products of CO2 reduction require tens of hours to obtain the dependence of product distribution on applied potential. As a consequence, there is a need to develop novel analytical approaches that can reduce this analysis time down to about an hour. We report here the design, construction, and operation of a novel differential electrochemical mass spectrometer (DEMS) cell geometry that enables the partial current densities of volatile electrochemical reaction products to be quantified in real time. The capabilities of the novel DEMS cell design are demonstrated by carrying out the electrochemical reduction of CO2 over polycrystalline copper. The reaction products are quantified in real time as a function of the applied potential during linear sweep voltammetry, enabling the product spectrum produced by a given electrocatalyst to be determined as a function of applied potential on a time scale of roughly 1 h. PMID- 26153830 TI - Cone Calix[4]arenes with Orientable Glycosylthioureido Groups at the Upper Rim: An In-Depth Analysis of Their Symmetry Properties. AB - The two glycoclusters alpha- and beta-d-mannosylthioureidocalix[4]arenes 1 and 2 in the cone geometry have been submitted to a conformational investigation with the DFT approach at the standard B3LYP/6-31G(d) level and using a water continuum solvent model. After a reasoned choice of the level of calculation and the evaluation of the properties of the monomeric components of 1 and 2, the intrinsic conformational properties of cone calix[4]arenes with orientable groups at the upper rim were thoroughly analyzed. From the possible combinations of the directions that the groups may assume, 10 different geometries derive, all chiral. These geometries are interchangeable through two different processes, named breathing equilibrium and arrow rotation, that allow a dense network connection among them. When the modeling of whole macrocycles 1 and 2 was performed, a huge difference in their conformational behavior that heavily influences the presentation mode of their saccharidic moieties was found. PMID- 26153831 TI - Justifying our existence. PMID- 26153832 TI - How effective are common ENT operations? AB - OBJECTIVE: To review the literature on the outcomes of ENT operations in order to assess whether ENT operations are effective. METHODS: The value of evidence-based medicine in relation to ENT was appraised, as was the perception of effectiveness. Literature on common ENT operations, including grommet insertion, tonsillectomy and adenoidectomy, and correction of the nasal septum, was evaluated. RESULTS AND CONCLUSION: When evaluating the effectiveness of ENT operations, the patient's overall condition and improvements after surgery should be measured. Objective and subjective factors should both be considered as good evidence, especially with the increasing role that evidence-based medicine plays in decisions of whether to operate. The literature review provides evidence that ENT operations are effective. PMID- 26153833 TI - Otomastoiditis caused by non-tuberculous mycobacteria: report of 16 cases, 3 with infection intracranially. AB - OBJECTIVE: To analyse the clinical presentation, treatment and outcome in patients diagnosed with otomastoiditis caused by non-tuberculous mycobacteria. METHODS: A retrospective case review of 16 patients diagnosed with otomastoiditis caused by non-tuberculous mycobacteria from 2000 to 2012 was conducted in a hospital and tertiary referral centre in Sweden. The main outcome measures were microbiology findings, and surgical and medical interventions and outcomes. In addition, the relevant literature was reviewed. RESULTS: In three patients with otomastoiditis, the disease had spread intracranially. The bacteriological findings revealed Mycobacterium abscessus (n = 12), Mycobacterium fortuitum (n = 2) and Mycobacterium avium complex (n = 2). Surgical treatment was undertaken in all but three patients, including exploration of the temporal lobe in one patient. Systemic antibiotic treatment was given to all but one patient. Eight patients healed completely. Eight patients developed hearing loss. Two patients had relapse of the mycobacterial infection several months after the antibiotic treatment had been discontinued. CONCLUSION: Non-tuberculous otomastoiditis is a severe ear disease with challenging considerations, and should be treated aggressively in order to avoid morbidity. PMID- 26153834 TI - Regrowth of the adenoids after adenoidectomy down to the pharyngobasilar fascial surface. AB - OBJECTIVES: This study aimed to explore adenoid regrowth after transoral power assisted adenoidectomy down to the pharyngobasilar fascial surface. METHODS: Transoral adenoidectomy down to the pharyngobasilar fascia surface was performed on 39 patients under endoscopic guidance, using a power-assisted system. The operation time, amount of blood loss and iatrogenic injury, presence of complications, and success and regrowth rates were recorded to assess the feasibility, safety and effectiveness of our surgical technique. RESULTS: In this adenoidectomy procedure, the pharyngobasilar fascia was left intact. The estimated blood loss was 5-50 ml (mean 15 ml), and the success rate was 97.3 per cent. Early complications occurred in 2.3 per cent of patients, while no long term complications occurred in the cohort. No regrowth was found in the follow-up assessments, which were performed for 18-36 months after surgery. CONCLUSION: Adenoid regrowth was rare after adenoidectomy down to the pharyngobasilar fascial surface. The pharyngobasilar fascia can therefore be considered a surgical boundary for adenoidectomy. PMID- 26153835 TI - Incidence of malignancy in solitary thyroid nodules. AB - OBJECTIVES: This study aimed to investigate the prevalence and clinical significance of solitary thyroid nodules in patients who underwent thyroid surgery. METHODS: A retrospective review was performed of the case notes of all adult patients who underwent thyroid surgery from January 2003 to December 2009. All patients with solitary thyroid nodules identified by ultrasonography were included. RESULTS: In total, 225 patients underwent thyroid surgery. The prevalence of solitary thyroid nodules was 27.1 per cent (61 out of 225 patients). Seventy-two per cent of patients were women and the mean age at presentation was 52 +/- 16 years. In all, 75.4 per cent of solitary nodules had neoplastic pathology and the malignancy rate was 34.4 per cent. The sensitivity and specificity of fine needle aspiration cytology for neoplasm detection were 73.9 per cent and 80.0 per cent, respectively. There was no association between the various ultrasonography parameters and malignancy risk (p > 0.05). CONCLUSION: Solitary thyroid nodules should be investigated thoroughly with a high index of suspicion because there is a high probability (34.0 per cent) of malignancy. PMID- 26153836 TI - Routine non-thyroid head and neck cytology in a large UK centre: clinical utility and pitfalls. AB - OBJECTIVE: This study aimed to examine the performance of head and neck cytology at Nottingham University Hospitals between 2009 and 2010. METHODS: Cases were extracted from the Winpath pathology reporting system and correlations were investigated between results and the histological and clinical outcomes. Specimen adequacy and the sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of the cytology tests were calculated. RESULTS: In all, 19.7 per cent of aspirates were judged to be inadequate. The absolute and relative sensitivities of head and neck cytology were 87.0 per cent and 89.0 per cent, respectively, and the absolute and relative specificities were 99.0 per cent and 97.0 per cent, respectively. The positive predictive values were 99.0 per cent and 96.0 per cent and the negative predictive values were 92.0 per cent and 92.0 per cent for a diagnostic accuracy of 94.5 per cent and 93.0 per cent. The performance was consistent with previous reports and superior to that of a recent UK series. The high rate of inadequate samples is, however, a concern. CONCLUSION: Head and neck cytology is a robust technique at our institution, although there are certain problem areas. There is room for improvement in the technical quality of fine needle aspiration. PMID- 26153837 TI - Expression of a disintegrin and metalloproteinase-33 protein in vocal fold polyps. AB - BACKGROUND: This study aimed to evaluate the association of a disintegrin and metalloproteinase-33 protein ('ADAM-33') expression in vocal polyp formation and to determine its correlation with clinical characteristics. METHODS: Medical charts and histological sections of 32 patients diagnosed with vocal polyps who underwent surgery were analysed. Controls were histopathologically normal vocal fold tissues obtained from 36 patients who underwent surgery for laryngeal squamous cell carcinoma. Immunohistochemical staining was performed to detect ADAM-33 expression in epithelial cells, stroma and vessels. RESULTS: All epithelial, stromal and vascular staining scores were significantly greater in polyp tissue than in controls (p < 0.001). Stromal ADAM-33 staining scores were higher in vocal polyp patients with a symptom duration of less than six months (p < 0.05). Vocal overuse or the presence of reflux symptoms, sinonasal symptoms or allergy did not affect ADAM-33 immunostaining scores (p = 0.05). CONCLUSION: In this study, ADAM-33 immunostaining was significantly increased in vocal polyps. Therefore, over-expression of this protein may be associated with vocal polyp pathogenesis. PMID- 26153838 TI - Patient perception of a randomised, controlled trial of laryngeal reinnervation versus thyroplasty for unilateral vocal fold paralysis. AB - OBJECTIVES: To explore unilateral vocal fold paralysis patients' perception of a proposed randomised, controlled trial of laryngeal reinnervation versus thyroplasty, and to identify patients' concerns regarding their voice. METHODS: Seventeen patients from five voice clinics in London were identified as being eligible for the randomised, controlled trial. Eleven of these patients (9 females and 2 males; age range, 18-65 years) were interviewed using a semi structured topic guide (they were given a minimum of 2 weeks to read through the study information sheet). The interviews were recorded, transcribed and analysed using thematic analysis. RESULTS: The patients were satisfied with the clarity of the information sheet. Most of them perceived that reinnervation was a more 'attractive' option than thyroplasty. This may have been the result of certain phraseology used in the information sheet and by recruiters. Patients' main concern was reduced voice strength and the effects of this on work and social life. CONCLUSION: Phraseology that needed changing was identified; these changes may optimise the recruitment process for a trial. We propose using the voice handicap index 10 as the primary measure of outcome in the proposed randomised, controlled trial. PMID- 26153839 TI - Hand-grip strength does not correlate with treatment-related weight loss in patients with head and neck cancer. AB - BACKGROUND: Hand-grip strength has been shown to be a reliable predictor of health outcomes. However, evidence supporting its use as an indicator of nutritional status is inconsistent. This study investigated its use in monitoring nutritional status in patients with head and neck cancer. METHODS: A prospective audit of patients treated for head and neck cancer was undertaken at four centres over a three-month period in 2009. Nutritional outcomes were collected at 3, 6 and 12 months, and the data were statistically analysed. RESULTS: Data from 114 patients showed that mean weight, but not hand-grip strength, fell significantly at 3, 6 and 12 months post-treatment (p < 0.003 vs p < 0.126). CONCLUSION: A fall in weight does not coincide with a drop in hand-grip strength in patients receiving treatment for head and neck cancer. Hand-grip strength may therefore not be of benefit in the nutritional assessment of these patients and should not be part of routine assessment. PMID- 26153840 TI - Isolated herpes simplex in the adult larynx as a rare complication of methotrexate-induced immunosuppression. AB - OBJECTIVE: This report describes the clinical presentation and management of a rare case of herpes simplex virus infection in the larynx of a patient treated with methotrexate. CASE REPORT: We report a case of a clinically suspicious laryngeal lesion in an 82-year-old woman who started methotrexate treatment for rheumatoid arthritis. Shortly afterwards she developed dysphonia, which worsened over four months. On microlaryngoscopy, there was bilateral erythema and ulceration of the vocal folds. No other mucocutaneous lesions or systemic features were present. Biopsies revealed herpes simplex virus infection of the vocal folds; there was complete resolution with oral aciclovir. A brief literature review for this rare entity is presented and the diagnostic challenges arising from under-recognition of atypical presentations are discussed. CONCLUSION: To our knowledge, this is the first report of a rare complication of herpes simplex virus infection in the context of methotrexate-induced immunosuppression. It may present therapeutic challenges for conditions which rely on immunosuppressive treatments. PMID- 26153841 TI - Potential airway compromise secondary to impacted Wharton's duct calculus: a noteworthy phenomenon. AB - OBJECTIVES: This case report describes a patient who suffered an acute, severe complication of unilateral submandibular sialolithiasis, the disease process and management of these patients. CASE REPORT: A 70-year-old woman was under investigation for a recurrent, painful right submandibular swelling and subsequently presented with an acute exacerbation. She exhibited symptoms of acute submandibular sialadenitis, and also reported breathing difficulty and a change in voice quality. Computed tomography imaging showed that this was caused by a submandibular gland duct sialolith, with inflammation extending to the ipsilateral supraglottis. She was treated medically and the stone was removed when the inflammation had stabilised. CONCLUSION: This case highlights the need to thoroughly assess patients with neck swellings, especially when symptoms are atypical, to avoid life-threatening complications. PMID- 26153842 TI - Barriers to and Facilitators of Moving Miscarriage Management Out of the Operating Room. AB - CONTEXT: Miscarriage care can safely and effectively be offered in appropriately equipped offices and emergency departments. However, it is often treated in the operating room, which limits access to timely, cost-effective and high-quality care. METHODS: Between May 2013 and January 2014, in-depth interviews were conducted with 30 staff holding diverse roles at 15 medical offices and emergency departments with the aim of exploring barriers to and facilitators of offering miscarriage care, and identifying methods for expanding care. On-site observations were also conducted at four facilities. All data were transcribed, iteratively coded and analyzed using qualitative techniques. RESULTS: Similar barriers to and facilitators of providing miscarriage care were identified across facility types. Barriers were physician preference for providing care in the operating room, the similarity of miscarriage management and abortion procedures, the limited availability of support staff, difficulties integrating miscarriage management into patient scheduling and flow, and uncertainty about responding to women's emotional needs. Facilitators were a commitment to evidence-based medicine, insurance coverage of miscarriage, offering other procedures of similar complexity and the minimal resources needed for miscarriage care. Resources needed to expand miscarriage services included a medically trained "champion," best practices for implementing services, persistence and patience, training, clear protocols, and systems for tracking equipment and supplies. CONCLUSIONS: Miscarriage care was viewed as neither resource-intensive nor technically complex to provide. Although it may be emotionally and politically challenging to offer, effective strategies are available for expanding the scope of miscarriage care offered in multiple settings. PMID- 26153843 TI - A CO32--containing, dimanganese-substituted silicotungstate trimer, K9[H14{SiW10MnIIMnIIIO38}3(CO3)].39H2O. AB - An unprecedented silicotungstate trimer K(9)[H(14){SiW(10)Mn(II)Mn(III)O(38)}(3)(CO(3))].39H(2)O (1) has been successfully synthesized, in which the CO(3)(2-) resides inside the three Keggin {SiW(10)Mn(II)Mn(III)O(38)} units and the three O atoms serve as MU(2)-O atoms to connect with three Mn(III). Magnetic investigation indicates that 1 exhibits antiferromagnetic coupling. PMID- 26153844 TI - Comparison of Guy and Clinical Research Office of the Endourological Society Nephrolithometry Scoring Systems for Predicting Stone-Free Status and Complication Rates After Percutaneous Nephrolithotomy: A Single Center Study with 437 Cases. AB - PURPOSE: To compare the Guy and Clinical Research Office of the Endourological Society (CROES) scoring systems in predicting postpercutaneous nephrolithotomy (PCNL) stone-free rate and complications. PATIENTS AND METHODS: A total of 437 patients who underwent PCNL for renal stones were included in the recent retrospective study. All stones were evaluated with CT preoperatively. Mean stone diameter was 701.52+/-510.65 mm(2). Guy and CROES nephrolithometry scores were calculated for each patient, and their correlation with stone-free status, operative and fluoroscopy time, and length of hospital stay was evaluated. Post PCNL stone status was evaluated with plain radiography of the kidneys, ureters, and bladder. Postoperative complications were graded according to the modified Clavien classification, and the correlation of both scoring systems with postoperative complications was also investigated. RESULTS: The mean Guy grade was 2.28+/-1.12, and the mean CROES score was 196.92+/-65.89. The overall stone free rate was 75.1%. There was a significant correlation between the Guy stone score (GSS) and CROES score and stone-free status (P<0.001, P<0.001). Also, both scoring systems were correlated with operative time (P<0.001, P<0.001) and length of hospital stay (P=0.002, P=0.01). The overall complication rate was 34.6%, with most being modified Clavien grade I and grade II. Both scoring systems were significantly correlated with complication rates. Regression analysis showed that both scoring systems were significantly associated with stone-free rates, estimated blood loss (EBL) (>250 mL), and operative time. CONCLUSION: Both GSS and CROES nomograms had comparable accuracies in predicting post-PCNL stone-free status. Different from the previous reports, our results showed that both nomograms were predictive of overall complications, EBL, and operative time. PMID- 26153845 TI - Abuse-Deterrent Formulations of Prescription Opioids. PMID- 26153846 TI - Linking the Molecular Signature of Heteroatomic Dissolved Organic Matter to Watershed Characteristics in World Rivers. AB - Large world rivers are significant sources of dissolved organic matter (DOM) to the oceans. Watershed geomorphology and land use can drive the quality and reactivity of DOM. Determining the molecular composition of riverine DOM is essential for understanding its source, mobility and fate across landscapes. In this study, DOM from the main stem of 10 global rivers covering a wide climatic range and land use features was molecularly characterized via ultrahigh resolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). FT-ICR mass spectral data revealed an overall similarity in molecular components among the rivers. However, when focusing specifically on the contribution of nonoxygen heteroatomic molecular formulas (CHON, CHOS, CHOP, etc.) to the bulk molecular signature, patterns relating DOM composition and watershed land use became apparent. Greater abundances of N- and S-containing molecular formulas were identified as unique to rivers influenced by anthropogenic inputs, whereas rivers with primarily forested watersheds had DOM signatures relatively depleted in heteroatomic content. A strong correlation between cropland cover and dissolved black nitrogen was established when focusing specifically on the pyrogenic class of compounds. This study demonstrated how changes in land use directly affect downstream DOM quality and could impact C and nutrient cycling on a global scale. PMID- 26153847 TI - ARPES measurements of the superconducting gap of Fe-based superconductors and their implications to the pairing mechanism. AB - Its direct momentum sensitivity confers to angle-resolved photoemission spectroscopy (ARPES) a unique perspective in investigating the superconducting gap of multi-band systems. In this review we discuss ARPES studies on the superconducting gap of high-temperature Fe-based superconductors. We show that while Fermi-surface-driven pairing mechanisms fail to provide a universal scheme for the Fe-based superconductors, theoretical approaches based on short-range interactions lead to a more robust and universal description of superconductivity in these materials. Our findings are also discussed in the broader context of unconventional superconductivity. PMID- 26153848 TI - Potential Danger of Pre-Pump Clamping on Negative Pressure-Associated Gaseous Microemboli Generation During Extracorporeal Life Support--An In Vitro Study. AB - The objectives of this study were to investigate the relationship between revolution speed of a conventional centrifugal pump and negative pressure at the inlet of the pump by clamping the tubing upstream of the pump, and to verify whether negative pressure leads to gaseous microemboli (GME) production in a simulated adult extracorporeal life support (ECLS) system. The experimental circuit, including a Maquet Rotaflow centrifugal pump and a Medos Hilite 7000 LT polymethyl-pentene membrane oxygenator, was primed with packed red blood cells (hematocrit 35%). Negative pressure was created in the circuit by clamping the tubing upstream of the pump for 10 s, and then releasing the clamp. An emboli detection and classification quantifier was used to record GME volume and count at pre-oxygenator and post-oxygenator sites, and pressure and flow rate data were collected using a custom-based data acquisition system. All trials were conducted at 36 degrees C at revolution speeds of 2000-4000 rpm (500 rpm increment). The flow rates were 1092.5-4708.4 mL/min at the revolution speeds of 2000-4000 rpm. Higher revolution speed generated higher negative pressure at the pre-pump site when clamping the tubing upstream of the pump (-108.3 +/- 0.1 to -462.0 +/- 0.5 mm Hg at 2000-4000 rpm). Moreover, higher negative pressure was associated with a larger number and volume of GME at pre-oxygenator site after de-clamp (GME count 10,573 +/- 271 at pre-oxygenator site at 4000 rpm). The results showed that there was a potential danger of delivering GME to the patient when clamping pre-pump tubing during ECLS using a centrifugal pump. Our results warrant further clinical studies to investigate this phenomenon. PMID- 26153849 TI - The complete chloroplast genome sequence of medicinal plant Pinellia ternata. AB - Pinellia ternata is an important medicinal plant used in the treatment of cough, to dispel phlegm, to calm vomiting and to terminate early pregnancy, as an anti ulcer and anti-tumor medicine. In this study, we found that the complete chloroplast genome of Pinellia ternata was 164 013 bp in length, containing a pair of inverted repeats of 25 625 bp separated by a large single-copy region and a small single-copy region of 89 783 bp and 22 980 bp, respectively. The chloroplast genome encodes 132 predicted functional genes, including 87 protein coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The chloroplast DNA is GC-rich (36.7%). The phylogenetic analysis showed a strong sister relationship with Colocasia esculenta, which also strongly supports the position of Pinellia ternata. The complete chloroplast genome sequence of Pinellia ternata reported here has the potential to advance population and phylogenetic studies of this medicinal plant. PMID- 26153850 TI - Effects of different roughage sources and feeding levels on adipogenesis of ovine adipocytes. AB - The objective of the present study was to conduct an adipogenic evaluation of different roughage sources and feeding levels during ruminant adipocyte differentiation in vitro. Six wether sheep were divided into a timothy hay feeding group (TFG, n = 3) and an Italian ryegrass straw feeding group (IFG, n = 3). The sheep were fed high-roughage (HR), medium roughage (MR) and low-roughage (LR) diets in a one-way layout design each over a 6-day period. Sheep serum samples collected on the last day of each dietary treatment were added to an adipogenic induction medium for differentiation of preadipocytes derived from sheep subcutaneous adipose tissue. The cytoplasmic lipid accumulations in the TFG serum-treated preadipocytes were significantly higher than those of the IFG-serum treated preadipocytes on day 12. Messenger RNA expression of CCAAT/enhancer binding protein (C/EBP)-alpha, C/EBP-beta, C/EBP-delta, fatty-acid-binding protein (aP2) and stearoyl-coenzyme A desaturase (SCD) were regulated by each serum treatment. This study shows that different roughage source diets and roughage-to-concentrate ratio diets can regulate adipocyte differentiation via ruminant blood composition. PMID- 26153852 TI - Preparation of "dummy" l-phenylalanine molecularly imprinted microspheres by using ionic liquid as a template and functional monomer. AB - In this study, dummy imprinting technology was employed for the preparation of l phenylalanine-imprinted microspheres. Ionic liquids were utilized as both a "dummy" template and functional monomer, and 4-vinylpyridine and ethylene glycol dimethacrylate were used as the assistant monomer and cross-linker, respectively, for preparing a surface-imprinted polymer on poly(divinylbenzene) microspheres. By the results obtained by theoretical investigation, the interaction between the template and monomer complex was improved as compared with that between the template and the traditional l-phenylalanine-imprinted polymer. The batch experiments indicated that the imprinting factor reached 2.5. Scatchard analysis demonstrated that the obtained "dummy" molecularly imprinted microspheres exhibited an affinity of 77.4 M.10-4 , significantly higher that of a traditional polymer directly prepared by l-phenylalanine, which is in agreement with theoretical results. Competitive adsorption experiments also showed that the molecularly imprinted polymer with the dummy template effectively isolated l phenylalanine from l-histidine and l-tryptophan with separation factors of 5.68 and 2.68, respectively. All these results demonstrated that the polymerizable ionic liquid as the dummy template could enhance the affinity and selectivity of molecularly imprinted polymer, thereby promoting the development of imprinting technology for biomolecules. PMID- 26153851 TI - The UCLA Study of Children with Moderate-to-Severe Traumatic Brain Injury: Event Related Potential Measure of Interhemispheric Transfer Time. AB - Traumatic brain injury (TBI) frequently results in diffuse axonal injury and other white matter damage. The corpus callosum (CC) is particularly vulnerable to injury following TBI. Damage to this white matter tract has been associated with impaired neurocognitive functioning in children with TBI. Event-related potentials can identify stimulus-locked neural activity with high temporal resolution. They were used in this study to measure interhemispheric transfer time (IHTT) as an indicator of CC integrity in 44 children with moderate/severe TBI at 3-5 months post-injury, compared with 39 healthy control children. Neurocognitive performance also was examined in these groups. Nearly half of the children with TBI had IHTTs that were outside the range of the healthy control group children. This subgroup of TBI children with slow IHTT also had significantly poorer neurocognitive functioning than healthy controls-even after correction for premorbid intellectual functioning. We discuss alternative models for the relationship between IHTT and neurocognitive functioning following TBI. Slow IHTT may be a biomarker that identifies children at risk for poor cognitive functioning following moderate/severe TBI. PMID- 26153853 TI - Time perspective, socioeconomic status, and psychological distress in chronic pain patients. AB - Time perspective (TP) is a fundamental dimension of the psychological construction of time. It refers to a subjective experience and can be defined as the relationship that individuals and groups have with the present, past, and future. Studies have shown that it is interesting to take into account TP in the field of health, especially for the study of the psychological distress (PD) of individuals faced with aversive situations. We conducted a research, which aimed to explore the relationship between TP and PD in patients with chronic pain. A total of 264 first-time patients (72.3% women; mean age = 49 years) at CHU Timone (Marseille) pain center answered a questionnaire included TP, socioeconomic status, pain beliefs (PB), pain characteristics, and sociodemographic characteristics. Using hierarchical regression analyses adjusted to the characteristics of pain, sociodemographic characteristics, and PB, we can observe significant relationships between different components of TP, socioeconomic status, and PD. These results emphasize the importance of TP as psychosocial variable in the analysis of PD in patients with chronic pain. These results also lead us to point out the role of the socioeconomic status that predicts levels of PD. PMID- 26153854 TI - The surface structure of silver-coated gold nanocrystals and its influence on shape control. AB - Understanding the surface structure of metal nanocrystals with specific facet indices is important due to its impact on controlling nanocrystal shape and functionality. However, this is particularly challenging for halide-adsorbed nanocrystals due to the difficulty in analysing interactions between metals and light halides (for example, chloride). Here we uncover the surface structures of chloride-adsorbed, silver-coated gold nanocrystals with {111}, {110}, {310} and {720} indexed facets by X-ray absorption spectroscopy and density functional theory modelling. The silver-chloride, silver-silver and silver-gold bonding structures are markedly different between the nanocrystal surfaces, and are sensitive to their formation mechanism and facet type. A unique approach of combining the density functional theory and experimental/simulated X-ray spectroscopy further verifies the surface structure models and identifies the previously indistinguishable valence state of silver atoms on the nanocrystal surfaces. Overall, this work elucidates the thus-far unknown chloride-metal nanocrystal surface structures and sheds light onto the halide-induced growth mechanism of anisotropic nanocrystals. PMID- 26153855 TI - Creating Anti-icing Surfaces via the Direct Immobilization of Antifreeze Proteins on Aluminum. AB - Cryoprotectants such as antifreeze proteins (AFPs) and sugar molecules may provide a solution for icing problems. These anti-icing substances protect cells and tissues from freezing by inhibiting ice formation. In this study, we developed a method for coating an industrial metal material (aluminum, Al) with AFP from the Antarctic marine diatom, Chaetoceros neogracile (Cn-AFP), to prevent or delay ice formation. To coat Al with Cn-AFP, we used an Al-binding peptide (ABP) as a conjugator and fused it with Cn-AFP. The ABP bound well to the Al and did not considerably change the functional properties of AFP. Cn-AFP-coated Al (Cn-AFP-Al) showed a sufficiently low supercooling point. Additional trehalose coating of Cn-AFP-Al considerably delayed AFP denaturation on the Al without affecting its antifreeze activity. This metal surface-coating method using trehalose-fortified AFP can be applied to other metals important in the aircraft and cold storage fields where anti-icing materials are critical. PMID- 26153856 TI - Corrigendum: Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. PMID- 26153857 TI - Systems biology: Network evolution hinges on history. PMID- 26153858 TI - Corrigendum: A diverse range of gene products are effectors of the type I interferon antiviral response. PMID- 26153859 TI - Progesterone receptor modulates ERalpha action in breast cancer. AB - Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-alpha (ERalpha) function and breast cancer prognosis. Here we show that PR is not merely an ERalpha-induced gene target, but is also an ERalpha associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERalpha to direct ERalpha chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen mediated growth of ERalpha(+) cell line xenografts and primary ERalpha(+) breast tumour explants, and had increased anti-proliferative effects when coupled with an ERalpha antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ERalpha(+) breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERalpha chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions. PMID- 26153860 TI - Timing and climate forcing of volcanic eruptions for the past 2,500 years. AB - Volcanic eruptions contribute to climate variability, but quantifying these contributions has been limited by inconsistencies in the timing of atmospheric volcanic aerosol loading determined from ice cores and subsequent cooling from climate proxies such as tree rings. Here we resolve these inconsistencies and show that large eruptions in the tropics and high latitudes were primary drivers of interannual-to-decadal temperature variability in the Northern Hemisphere during the past 2,500 years. Our results are based on new records of atmospheric aerosol loading developed from high-resolution, multi-parameter measurements from an array of Greenland and Antarctic ice cores as well as distinctive age markers to constrain chronologies. Overall, cooling was proportional to the magnitude of volcanic forcing and persisted for up to ten years after some of the largest eruptive episodes. Our revised timescale more firmly implicates volcanic eruptions as catalysts in the major sixth-century pandemics, famines, and socioeconomic disruptions in Eurasia and Mesoamerica while allowing multi millennium quantification of climate response to volcanic forcing. PMID- 26153861 TI - Intersecting transcription networks constrain gene regulatory evolution. AB - Epistasis-the non-additive interactions between different genetic loci-constrains evolutionary pathways, blocking some and permitting others. For biological networks such as transcription circuits, the nature of these constraints and their consequences are largely unknown. Here we describe the evolutionary pathways of a transcription network that controls the response to mating pheromone in yeast. A component of this network, the transcription regulator Ste12, has evolved two different modes of binding to a set of its target genes. In one group of species, Ste12 binds to specific DNA binding sites, while in another lineage it occupies DNA indirectly, relying on a second transcription regulator to recognize DNA. We show, through the construction of various possible evolutionary intermediates, that evolution of the direct mode of DNA binding was not directly accessible to the ancestor. Instead, it was contingent on a lineage specific change to an overlapping transcription network with a different function, the specification of cell type. These results show that analysing and predicting the evolution of cis-regulatory regions requires an understanding of their positions in overlapping networks, as this placement constrains the available evolutionary pathways. PMID- 26153862 TI - Symbiosis: Receptive to infection. PMID- 26153864 TI - Corrigendum: Passenger deletions generate therapeutic vulnerabilities in cancer. PMID- 26153863 TI - Receptor-mediated exopolysaccharide perception controls bacterial infection. AB - Surface polysaccharides are important for bacterial interactions with multicellular organisms, and some are virulence factors in pathogens. In the legume-rhizobium symbiosis, bacterial exopolysaccharides (EPS) are essential for the development of infected root nodules. We have identified a gene in Lotus japonicus, Epr3, encoding a receptor-like kinase that controls this infection. We show that epr3 mutants are defective in perception of purified EPS, and that EPR3 binds EPS directly and distinguishes compatible and incompatible EPS in bacterial competition studies. Expression of Epr3 in epidermal cells within the susceptible root zone shows that the protein is involved in bacterial entry, while rhizobial and plant mutant studies suggest that Epr3 regulates bacterial passage through the plant's epidermal cell layer. Finally, we show that Epr3 expression is inducible and dependent on host perception of bacterial nodulation (Nod) factors. Plant-bacterial compatibility and bacterial access to legume roots is thus regulated by a two-stage mechanism involving sequential receptor-mediated recognition of Nod factor and EPS signals. PMID- 26153866 TI - The prognostic value of histopathology on lingual nerve neurosensory recovery after micro-neurosurgery. AB - OBJECTIVE: Micro-neurosurgical repair is considered in permanent nerve damage but the outcome is unpredictable. We examined if histopathologic parameters of traumatic neuromas have a prognostic value for recovery in relation to lingual nerve micro-neurosurgery. MATERIALS AND METHODS: Retrospective case study on neurosensory recovery after micro-neurosurgery. Outcome variables were as follows: pain perception, two-point discrimination, and sum score of perception, before and 12 months after micro-neurosurgery. Predictive histopathology variables included size, nerve tissue, and inflammation. Statistics are as follows: logistic and correlation analyses (P < 0.05). RESULTS: Sixty-five patients with lingual nerve damage were included in the study. Improved two-point discrimination was associated with small size of resected tissue (P = 0.0275). No normal appearing distal nerve tissue was associated with improved sum score of perception (P = 0.0185), higher final sum score of perception value (P = 0.0475) and final pain perception (P = 0.0324). Foreign body reaction was associated with no final pain perception (P = 0.0492). CONCLUSIONS: Small size, absence of distal nerve tissue, and no foreign body reaction were associated with improvement of the neurosensory functions. CLINICAL RELEVANCE: Histological parameters of the traumatic neuromas in routine preparation appeared to have some prognostic value for neurosensory functions as improvement of the neurosensory functions was associated with small size of resected tissue, no distal normal appearing nerve tissue, and no foreign body reaction. PMID- 26153865 TI - Revealing the Function and the Structural Model of Ts4: Insights into the "Non Toxic" Toxin from Tityus serrulatus Venom. AB - The toxin, previously described as a "non-toxic" toxin, was isolated from the scorpion venom of Tityus serrulatus (Ts), responsible for the most severe and the highest number of accidents in Brazil. In this study, the subtype specificity and selectivity of Ts4 was investigated using six mammalian Nav channels (Nav1.2 >Nav1.6 and Nav1.8) and two insect Nav channels (DmNav1 and BgNav). The electrophysiological assays showed that Ts4 specifically inhibited the fast inactivation of Nav1.6 channels, the most abundant sodium channel expressed in the adult central nervous system, and can no longer be classified as a "non-toxic peptide". Based on the results, we could classify the Ts4 as a classical alpha toxin. The Ts4 3D-structural model was built based on the solved X-ray Ts1 3D structure, the major toxin from Ts venom with which it shares high sequence identity (65.57%). The Ts4 model revealed a flattened triangular shape constituted by three-stranded antiparallel beta-sheet and one alpha-helix stabilized by four disulfide bonds. The absence of a Lys in the first amino acid residue of the N-terminal of Ts4 is probably the main responsible for its low toxicity. Other key amino acid residues important to the toxicity of alpha- and beta-toxins are discussed here. PMID- 26153868 TI - Erratum to: a pragmatic approach to infants with Robin sequence: a retrospective cohort study and presence of a treatment algorithm. PMID- 26153867 TI - Evaluation of a biomarker based blood test for monitoring surgical resection of oral squamous cell carcinomas. AB - INTRODUCTION: The potential use of determination of biomarkers in blood for the monitoring of surgical removal of oral squamous cell carcinomas (OSCC) was evaluated using the epitope detection in monocytes (EDIM) technology. MATERIALS AND METHODS: In tumor specimen, elevated Apo10 and transketolase-like 1 (TKTL1) expression was analyzed by immunohistochemistry. Apo10 and TKTL1 biomarkers have been used prospectively for EDIM blood test in patients with primary and/or recurrent OSCC (n = 92) before surgery and after curative tumor resection (n = 45). RESULTS: There were highly significant (p < 0.0001) correlations found between EDIM blood scores and the tissue expression of both biomarkers measured by immunohistochemistry (Apo10: n = 89/92, 97%; TKTL1: n = 90/92, 98%). EDIMApo10 and EDIM-TKTL1 scores were positive in 92% (EDIM-Apo10: n = 85/92) and 93% (EDIM TKTL1: n = 86/92), respectively, in patients with OSCC before surgery. The combined score EDIM-Apo10/EDIM-TKTL1 increased significantly the detection rate of tumors to 97% (n = 89/92). After surgery, the EDIM-TKTL1 and EDIMApo10 scores significantly decreased in 75.6 and 86.7% of the patients (p < 0.0001), respectively, in the aftercare. CONCLUSIONS: The correlation of TKTL1 and Apo10 immunohistochemistry with the blood test results indicates that the EDIM blood test could serve as a non-invasive diagnostic tool (liquid biopsy) to assess surgical removal of OSCC by determination of two biomarkers. CLINICAL RELEVANCE: This is the first study that has been demonstrated a reliable and successful monitoring of OSCC cancer patients by a blood test. The specific and significant decrease of EDIM-TKTL1 and EDIM-Apo10 scores after surgery could serve as a new tool for monitoring surgical removal of OSCC. PMID- 26153869 TI - Gene delivery with IFN-gamma-expression plasmids enhances the therapeutic effects of MSCs on DSS-induced mouse colitis. AB - OBJECTIVE: Interferon-gamma (IFN-gamma) is known to enhance the immunosuppressive properties of mesenchymal stem cells (MSCs). The aim of this study was to determine whether gene modification with IFN-gamma-expression plasmids could boost the therapeutic effects of MSCs on DSS-induced colitis. METHODS: We first reconstructed pcDNA3.1-IFNgamma plasmids, transfected them to human umbilical cord derived MSCs, and detected the basic characters of MSCs including immune phenotype, cell vitality, proliferation, apoptosis and cell cycle progression after transfection. Subsequently, we analyzed the inhibition effect of IFN-gamma MSCs on T cell proliferation in vitro. Finally, we induced colitis in female C57BL/6 mice by 3 % DSS treatment and evaluated the therapeutic efficacy of IFN gamma-MSCs on colitis. RESULTS: Transfection with pcDNA3.1-IFNgamma did not change the basic characters of MSCs. Interestingly, IFN-gamma-MSCs showed more potent immunosuppressive effects on the proliferation of T cells compared to normal MSCs. Furthermore, systemic infusion with IFN-gamma-MSCs more efficiently ameliorated DSS-induced mouse colitis including colitis-related ease of body weight, increase of colon length, decrease of disease activity index, and improvement of small intestine tissues structure. In addition, IFN-gamma-MSCs increased the populations of Foxp3(+) Tregs and Th2 cells both in mesenteric lymph node and spleen, upregulated indoleamine 2, 3-dioxygenase expression, and suppressed inflammatory cytokine production in mouse colon. CONCLUSIONS: Gene delivery with IFN-gamma-expression plasmids enhanced the therapeutic effects of MSCs on DSS-induced mouse colitis. This study provides an effective therapeutic strategy of MSCs for inflammatory diseases. PMID- 26153871 TI - Faculty diversity and inclusion program outcomes at an academic otolaryngology department. AB - OBJECTIVES/HYPOTHESIS: To describe a 10-year diversity initiative to increase the number of women and underrepresented minorities in an academic department of otolaryngology-head and neck surgery. STUDY DESIGN: Retrospective review. METHODS: A multifaceted approach was undertaken to recruit and retain women and underrepresented minority (URM) faculty: creation of a climate of diversity, aggressive recruitment, achievement of parity of salary at rank regardless of gender or minority status, provision of mentorship to women and URM faculty, and increasing the pipeline of qualified candidates. Primary outcomes measures included number of women and URM faculty, academic rank, and salary. RESULTS: From 2004 to 2014, the percentage of women clinical faculty increased from 5.8% to 23.7%; women basic science faculty increased from 11.1% to 37.5%. The number of women at associate professor rank increased from 0 to eight. During this period, underrepresented minority faculty increased in number from two to four; URM full professors increased in number from 0 to 1. In 2004, women earned 4% to 12% less than their male counterparts; there were no salary differences for URM. In 2014, salary was equal by rank and subspecialty training independent of gender or minority status. CONCLUSION: A comprehensive diversity and inclusion initiative has increased representation of women and URM faculty in an academic department of otolaryngology-head and neck surgery. However, there continue to be opportunities to further increase diversity. LEVEL OF EVIDENCE: N/A. PMID- 26153870 TI - Characterization of microRNA expression profiling in peripheral blood lymphocytes in rats with experimental autoimmune uveitis. AB - OBJECTIVE AND DESIGN: We aimed to investigate the alterations of microRNA (miRNA) genomics in peripheral blood lymphocytes in experimental autoimmune uveitis (EAU) rats versus control samples. MATERIALS/METHODS: Six Lewis rats received interphotoreceptor retinoid-binding protein (IRBP) emulsion to induce EAU. On day 12, peripheral blood lymphocytes were isolated, and total RNAs were extracted. Using microarray analysis, we analyzed the aberrant miRNAs, validated the relevant expression of differentially expressed miRNAs, and predicted the possible miRNA targets and signaling pathways. RESULTS: The results indicated that 36 miRNAs were upregulated and 31 miRNAs were downregulated in EAU rats versus normal samples. Real-time quantitative PCR substantiated a high degree of confidence for the differentially expressed miRNAs, and miRNA analyses showed the differentially expressed miRNA targets were involved not only in the multicellular organismal process and developmental process, but also in T cell receptor signaling pathway, B cell receptor signaling pathway and so on. CONCLUSIONS: Our findings show that the differentially expressed miRNAs in EAU rats were closely associated with immune signaling pathways and may be applied in early prevention, prognosis and possible therapy in uveitis, indicating that miRNAs play an important role in the development of uveitis. PMID- 26153872 TI - Interobserver reproducibility and agreement with original diagnosis in the categories "atypical" and "suspicious for malignancy" for bile and pancreatic duct brushings. AB - BACKGROUND: The Papanicolaou Society of Cytopathology has developed a set of guidelines which include a diagnostic scheme with the categories "atypical" and "suspicious for malignancy." These intermediate categories may help stratify risk of malignancy for samples obtained from the bile and pancreatic ducts. However, the reproducibility of these intermediate categories is currently unknown. METHODS: Twenty sequential brushing specimens of bile or pancreatic ducts from each of the categories "atypical" and "suspicious for malignancy" were identified and the slides retrieved. All 40 cases were reviewed independently by four cytopathologists blinded to the original diagnoses. Resulting review diagnoses were statistically analyzed for agreement and the Kappa statistic calculated. Agreement of the observers' diagnoses with original diagnoses was also evaluated. RESULTS: Interobserver agreement was graded as slight to fair with observers agreeing in about 50% of cases. The corresponding kappa statistic for the category "atypical" was 0.21 and 0.18 for the category "suspicious for malignancy." Reviewer agreement with the original reference diagnosis occurred in approximately one half of review diagnoses. CONCLUSION: Analysis of agreement shows that interobserver agreement was only slight to fair. Despite the categories "atypical" and "suspicious for malignancy" having distinct risks of malignancy (62% versus 74%), the reproducibility of these categories is relatively poor. A single intermediate category may improve reproducibility over the scheme proposed by the Papanicolaou Society of Cytopathology while maintaining an ability to stratify risk of malignancy. PMID- 26153873 TI - Cell-contact dependent inhibition of monocytes by airway epithelial cells and reversion by infection with Respiratory Syncytial Virus. AB - Airway epithelial cells (AEC) are the first line of defense against airborne infectious microbes and play an important role in regulating the local immune response. However, the interplay of epithelial cells and professional immune cells during both homeostasis and infection has only been partially studied. The present study was performed to determine how bronchial epithelial cells affect the activation of monocytes. Under healthy conditions, AECs were shown to inhibit reactivity of monocytes. We hypothesized that upon infection, monocytes might be released from inhibition by AECs. We report that direct contact of monocytes with unstimulated BEAS2B epithelial cells results in inhibition of TNF secretion by activated monocytes. In addition to the known soluble modulators, we show that cell contacts between epithelial cells and monocytes or macrophages also contribute to homeostatic inhibitory actions. We find AECs to express the inhibitory molecule PD-L1 and blockade of PD-L1 results in increased secretion of pro-inflammatory cytokines from monocytes. Contrary to the inhibitory activities during homeostasis, epithelial cells infected with Respiratory Syncitial Virus (RSV) induce a significant release of inhibition. However, release of inhibition was not due to modulation of PD-L1 expression in AECs. We conclude that airway epithelial cells control the reactivity of monocytes through direct and indirect interactions; however tonic inhibition can be reverted upon stimulation of AECs with RSV and thereof derived molecular patterns. The study confirms the important role of airway epithelial cells for local immune reactions. PMID- 26153874 TI - Changes of immunocytic phenotypes and functions from human colorectal adenomatous stage to cancerous stage: Update. AB - It is believed that chronic inflammation as seen in patients with ulcerative colitis significantly increases the colorectal cancer (CRC) risk and functions as the main driving force for the development of colitis associated CRC. Recently, increasing evidences suggest that inflammation is also involved in the processing of sporadic CRCs that mostly develop from the preformed adenomas through a long term progression. Within the adenoma/CRC tumor microenvironment, high dense immunocytes with significant phenotypic and functional changes have been observed. These cells might produce high level of inflammatory mediators and then affect the adenoma-cancer transition. In this review, we summarize the update on altered phenotypes and inflammatory mediators within the tumor microenvironment from the adenomatous stage to the cancerous stage, and discuss the significance of inflammatory mediators as biomarkers in predicating the progression from the premalignant adenoma lesion to the sporadic CRC lesion and the potential as therapeutic targets. PMID- 26153875 TI - Reaching clinically relevant outcome measures for new pharmacotherapy and immunotherapy of atopic eczema. AB - PURPOSE OF REVIEW: This article describes the core outcome set (COS) for atopic eczema trials. RECENT FINDINGS: COS describe a minimum set of outcomes to be assessed in a defined situation. COS are required to overcome the current situation of different trials using different endpoints with unclear/insufficient measurement properties resulting in incomparable trials. The global multi stakeholder Harmonising Outcomes Measures for Eczema initiative developed the Harmonising Outcomes Measures for Eczema roadmap as a generic framework for COS development. Following the establishment of a panel representing all stakeholders, a core set of outcome domains need to be selected based on systematic reviews and consensus methods. Outcome measurement instruments to assess these core domains need to be valid, reliable, and feasible. There is broad global consensus that clinical signs, quality of life, symptoms, and long term control of flares form the COS for atopic eczema trials. The Eczema Area and Severity Index is recommended to assess clinical signs in atopic eczema trials. Systematic reviews to identify adequate outcome measurement instruments for the other core outcome domains are underway. SUMMARY: Clinical signs should be assessed in all atopic eczema trials by at least the Eczema Area and Severity Index. Quality of life, symptoms, and flares should also be assessed in all atopic eczema trials by a valid, reliable, and feasible instrument. PMID- 26153877 TI - Vortex Keratopathy: Fabry Related or Amiodarone Induced? PMID- 26153878 TI - Digging for Buried Amino Acids Unearths New Protein Quality Control Treasure. AB - Proteins rely on three-dimensional structure for function, yet many proteins are marginally stable and prone to misfolding. In this issue of Structure, Brock et al. (2015) present a novel computational modeling method to gain insights into protein stability and misfolding. PMID- 26153879 TI - Biogenesis of Nascent High Density Lipoprotein Particles. AB - In this issue of Structure, Segrest et al. (2015) present a novel picture for the ABCA1-mediated lipid loading of lipid-poor apoA-I. PMID- 26153880 TI - From an SNP to a Disease: A Comprehensive Statistical Analysis. AB - Understanding and linking at the molecular level a disease phenotype to a specific genotype often requires going through a protein structure and function. In this issue of Structure, Gao et al. (2015) perform large scale analysis of available sequences and structural data for more than 6000 mutants representing more than 600 proteins to uncover some interesting structural effects of disease associated mutations. PMID- 26153881 TI - Effect of experimentally reduced distal sensation on postural response to hip abductor/ankle evertor muscle vibration. AB - This study assessed whether postural responses induced by vibratory perturbations of the hip abductors and ankle evertors, were modified when distal tactile sensation was experimentally reduced through cooling. Sixteen healthy subjects were investigated pre and post cooling. Subjects stood with their eyes closed with a stance width of 4 cm. A 2s vibratory stimulus was applied to the left or right hip abductor or ankle evertor muscle. The order of the site and side of the stimulation was randomised. The postural response to hip abductor and ankle evertor vibration was recorded using 3D motion analysis (Codamotion, Leicestershire). Medio-lateral centre of pressure motion was simultaneously recorded during quiet standing via a force plate (Kistler, UK). Pre-cooling people responded to unilateral ankle vibration with an ipsilateral translation and tilt of the pelvis, and an ipsilateral tilt of the trunk. People responded to unilateral hip vibration with a contralateral translation and tilt of the pelvis, and an ipsilateral tilt of the trunk. Following an experimental reduction in distal tactile sensation there was a significant reduction in the amplitude of pelvic tilt in response to ankle vibration (F(6.2)=P<0.05) and a significant increase in amplitude of pelvic tilt in response to hip vibration (F(5.2)=P<0.05). This suggests that the sensitivity to artificial stimulation of hip proprioception increases with distal cooling, possibly indicating a change in the gain/weighting placed upon sensory information from the hips. PMID- 26153882 TI - Isolated fat pad sign in acute elbow injury: is it clinically relevant? AB - An isolated fat pad sign (i.e. joint effusion without a visible fracture), commonly seen in acute elbow injury, is associated with occult fracture and treated as such. However, the clinical relevance of an isolated fat pad is unclear, thereby questioning the need for specialized follow-up. In this study, 111 patients (median age 15 years, interquartile range 9-27 years) with an isolated fat pad sign after acute elbow injury were included. The clinical relevance of an isolated fat pad sign was derived from descriptives on pain, elbow function, treatment change, number of revisits and recovery time after 1 week follow-up and long-term follow-up. Treatment alterations were rarely made and none of the patients needed an operative intervention; also, none of the patients had persistent symptoms. The median recovery time was 3 weeks (interquartile range 2-12 weeks). This study shows that, unless symptoms persist or worsen, regular follow-up at a specialized outpatient clinic is not needed. PMID- 26153883 TI - Identifying Suitable Locations for Mesophotic Hard Corals Offshore of Maui, Hawai'i. AB - Mesophotic hard corals (MHC) are increasingly threatened by a growing number of anthropogenic stressors, including impacts from fishing, land-based sources of pollution, and ocean acidification. However, little is known about their geographic distributions (particularly around the Pacific islands) because it is logistically challenging and expensive to gather data in the 30 to 150 meter depth range where these organisms typically live. The goal of this study was to begin to fill this knowledge gap by modelling and predicting the spatial distribution of three genera of mesophotic hard corals offshore of Maui in the Main Hawaiian Islands. Maximum Entropy modeling software was used to create separate maps of predicted probability of occurrence and uncertainty for: (1) Leptoseris, (2) Montipora, and (3) Porites. Genera prevalence was derived from the in situ presence/absence data, and used to convert relative habitat suitability to probability of occurrence values. Approximately 1,300 georeferenced records of the occurrence of MHC, and 34 environmental predictors were used to train the model ensembles. Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) values were between 0.89 and 0.97, indicating excellent overall model performance. Mean uncertainty and mean absolute error for the spatial predictions ranged from 0.006% to 0.05% and 3.73% to 17.6%, respectively. Depth, distance from shore, euphotic depth (mean and standard deviation) and sea surface temperature (mean and standard deviation) were identified as the six most influential predictor variables for partitioning habitats among the three genera. MHC were concentrated between Hanaka'o'o and Papawai Points offshore of western Maui most likely because this area hosts warmer, clearer and calmer water conditions almost year round. While these predictions helped to fill some knowledge gaps offshore of Maui, many information gaps remain in the Hawaiian Archipelago and Pacific Islands. This approach may be used to identify other potentially suitable areas for MHCs, helping scientists and resource managers prioritize sites, and focus their limited resources on areas that may be of higher scientific or conservation value. PMID- 26153884 TI - Replacing Non-Active Video Gaming by Active Video Gaming to Prevent Excessive Weight Gain in Adolescents. AB - OBJECTIVE: The aim of the current study was to evaluate the effects of and adherence to an active video game promotion intervention on anthropometrics, sedentary screen time and consumption of sugar-sweetened beverages and snacks among non-active video gaming adolescents who primarily were of healthy weight. METHODS: We assigned 270 gaming (i.e. >= 2 hours/week non-active video game time) adolescents randomly to an intervention group (n = 140) (receiving active video games and encouragement to play) or a waiting-list control group (n = 130). BMI SDS (SDS = adjusted for mean standard deviation score), waist circumference-SDS, hip circumference and sum of skinfolds were measured at baseline, at four and ten months follow-up (primary outcomes). Sedentary screen time, physical activity, consumption of sugar-sweetened beverages and snacks, and process measures (not at baseline) were assessed with self-reports at baseline, one, four and ten months follow-up. Multi-level-intention to treat-regression analyses were conducted. RESULTS: The control group decreased significantly more than the intervention group on BMI-SDS (beta = 0.074, 95%CI: 0.008;0.14), and sum of skinfolds (beta = 3.22, 95%CI: 0.27;6.17) (overall effects). The intervention group had a significantly higher decrease in self-reported non-active video game time (beta = -1.76, 95%CI: -3.20;-0.32) and total sedentary screen time (Exp (beta = 0.81, 95%CI: 0.74;0.88) than the control group (overall effects). The process evaluation showed that 14% of the adolescents played the Move video games every week >= 1 hour/week during the whole intervention period. CONCLUSIONS: The active video game intervention did not result in lower values on anthropometrics in a group of 'excessive' non-active video gamers (mean ~ 14 hours/week) who primarily were of healthy weight compared to a control group throughout a ten-month-period. Even some effects in the unexpected direction were found, with the control group showing lower BMI-SDS and skin folds than the intervention group. The intervention did result in less self-reported sedentary screen time, although these results are likely biased by social desirability. TRIAL REGISTRATION: Dutch Trial Register NTR3228. PMID- 26153885 TI - Mortality Attributable to Low Levels of Education in the United States. AB - BACKGROUND: Educational disparities in U.S. adult mortality are large and have widened across birth cohorts. We consider three policy relevant scenarios and estimate the mortality attributable to: (1) individuals having less than a high school degree rather than a high school degree, (2) individuals having some college rather than a baccalaureate degree, and (3) individuals having anything less than a baccalaureate degree rather than a baccalaureate degree, using educational disparities specific to the 1925, 1935, and 1945 cohorts. METHODS: We use the National Health Interview Survey data (1986-2004) linked to prospective mortality through 2006 (N=1,008,949), and discrete-time survival models, to estimate education- and cohort-specific mortality rates. We use those mortality rates and data on the 2010 U.S. population from the American Community Survey, to calculate annual attributable mortality estimates. RESULTS: If adults aged 25-85 in the 2010 U.S. population experienced the educational disparities in mortality observed in the 1945 cohort, 145,243 deaths could be attributed to individuals having less than a high school degree rather than a high school degree, 110,068 deaths could be attributed to individuals having some college rather than a baccalaureate degree, and 554,525 deaths could be attributed to individuals having anything less than a baccalaureate degree rather than a baccalaureate degree. Widening educational disparities between the 1925 and 1945 cohorts result in a doubling of attributable mortality. Mortality attributable to having less than a high school degree is proportionally similar among women and men and among non-Hispanic blacks and whites, and is greater for cardiovascular disease than for cancer. CONCLUSIONS: Mortality attributable to low education is comparable in magnitude to mortality attributable to individuals being current rather than former smokers. Existing research suggests that a substantial part of the association between education and mortality is causal. Thus, policies that increase education could significantly reduce adult mortality. PMID- 26153886 TI - Neuronal Interferon Signaling Is Required for Protection against Herpes Simplex Virus Replication and Pathogenesis. AB - Interferon (IFN) responses are critical for controlling herpes simplex virus 1 (HSV-1). The importance of neuronal IFN signaling in controlling acute and latent HSV-1 infection remains unclear. Compartmentalized neuron cultures revealed that mature sensory neurons respond to IFNbeta at both the axon and cell body through distinct mechanisms, resulting in control of HSV-1. Mice specifically lacking neural IFN signaling succumbed rapidly to HSV-1 corneal infection, demonstrating that IFN responses of the immune system and non-neuronal tissues are insufficient to confer survival following virus challenge. Furthermore, neurovirulence was restored to an HSV strain lacking the IFN-modulating gene, gamma34.5, despite its expected attenuation in peripheral tissues. These studies define a crucial role for neuronal IFN signaling for protection against HSV-1 pathogenesis and replication, and they provide a novel framework to enhance our understanding of the interface between host innate immunity and neurotropic pathogens. PMID- 26153888 TI - Neurocognitive Remediation Therapy for Depression: A Feasibility Study and Randomized Controlled Pilot Protocol Testing. AB - Major depression is the most prevalent psychiatric disorder with high relapse rates. When mood can improve or fully recover, the neurocognitive difficulties associated with depression often persist, preventing complete functional recovery. They have also been shown to predict relapse. The efficacy of neurocognitive remediation therapy (NCRT) to rehabilitate cognition has been demonstrated in several clinical populations but randomized controlled trials (RCTs) have not been conducted in depression. The present study aimed to test the feasibility and to conduct a pilot protocol testing for an RCT of computerized NCRT for inpatients with major depressive episode. The feasibility assessment demonstrated excellent acceptance of randomization and very satisfactory recruitment and compliance rates. The RCT procedures' assessment was overall consistent with a successful pilot study with the condition of protocol modification in terms of resources. Preliminary outcome data suggested specific NCRT efficacy to improve targeted neurocognitive processes in depression. PMID- 26153887 TI - Maternal Plane of Nutrition during Late Gestation and Weaning Age Alter Angus * Simmental Offspring Longissimus Muscle Transcriptome and Intramuscular Fat. AB - In model organisms both the nutrition of the mother and the young offspring could induce long-lasting transcriptional changes in tissues. In livestock, such changes could have important roles in determining nutrient use and meat quality. The main objective was to evaluate if plane of maternal nutrition during late gestation and weaning age alter the offspring's Longissimus muscle (LM) transcriptome, animal performance, and metabolic hormones. Whole-transcriptome microarray analysis was performed on LM samples of early (EW) and normal weaned (NW) Angus * Simmental calves born to grazing cows receiving no supplement [low plane of nutrition (LPN)] or 2.3 kg high-grain mix/day [medium plane of nutrition (MPN)] during the last 105 days of gestation. Biopsies of LM were harvested at 78 (EW), 187 (NW) and 354 (before slaughter) days of age. Despite greater feed intake in MPN offspring, blood insulin was greater in LPN offspring. Carcass intramuscular fat content was greater in EW offspring. Bioinformatics analysis of the transcriptome highlighted a modest overall response to maternal plane of nutrition, resulting in only 35 differentially expressed genes (DEG). However, weaning age and a high-grain diet (EW) strongly impacted the transcriptome (DEG = 167), especially causing a lipogenic program activation. In addition, between 78 and 187 days of age, EW steers had an activation of the innate immune system due presumably to macrophage infiltration of intramuscular fat. Between 187 and 354 days of age (the "finishing" phase), NW steers had an activation of the lipogenic transcriptome machinery, while EW steers had a clear inhibition through the epigenetic control of histone acetylases. Results underscored the need to conduct further studies to understand better the functional outcome of transcriptome changes induced in the offspring by pre- and post-natal nutrition. Additional knowledge on molecular and functional outcomes would help produce more efficient beef cattle. PMID- 26153889 TI - Chronic Low Back Pain: Perception and Coping With Pain in the Presence of Psychiatric Comorbidity. AB - This retrospective study investigated the influence of psychiatric comorbidity on pain perception and coping with pain in tertiary pain clinic patients, 427 treated for chronic low back pain (CLBP) and 629 for other forms of chronic pain (CG). No differences in psychosomatic dimensions were found between the two groups, but Italian Pain Questionnaire dimensions and intensity scores (t = 7.35; p < 0.0001) were higher in CLBP than in CG subjects. According to the Mini International Neuropsychiatric Interview, CLBP patients also had a higher prevalence of lifetime major depressive episodes (chi2 = 4.96; p < 0.05), dysthymic disorder (chi2 = 4.64; p < 0.05), suicide risk (chi2 = 10.43; p < 0.01), and agoraphobia (chi2 = 6.31; p < 0.05) than CG patients did. The Multidimensional Pain Inventory showed a close association between CLBP and both agoraphobia (chi2 = 3.74; p < 0.05) and dysfunctional coping style (chi2 = 8.25; p < 0.01), which increased disability. Both agoraphobia and lifetime depression were associated with an overall increase in dimensions and pain intensity in CLBP, but not in CG. PMID- 26153890 TI - Personality Disorders and Mindreading: Specific Impairments in Patients With Borderline Personality Disorder Compared to Other PDs. AB - The capacity of understanding mental states is a complex function which involves several components. Single components can be selectively impaired in specific clinical populations. It has been suggested that impairments in mindreading are central for borderline personality disorder (BPD). However, empirical findings are inconsistent, and it is debatable whether BPD presents a specific profile of mindreading impairments. The aim of this study is to compare BPD and other PDs in mindreading. Seventy-two patients with BPD and 125 patients with other PD diagnoses were assessed using the Metacognition Assessment Interview. BPD showed difficulties in two mindreading functions, differentiation and integration, even when the severity of psychopathology was controlled. These results suggest a specific mindreading impairment in BPD and a strong relationship between these impairments and the severity of psychopathology. PMID- 26153891 TI - Social Participation and Disaster Risk Reduction Behaviors in Tsunami Prone Areas. AB - This paper examines the relationships between social participation and disaster risk reduction actions. A survey of 557 households in tsunami prone areas in Phang Nga, Thailand was conducted following the 2012 Indian Ocean earthquakes. We use a multivariate probit model to jointly estimate the likelihood of undertaking three responses to earthquake and tsunami hazards (namely, (1) following disaster related news closely, (2) preparing emergency kits and/or having a family emergency plan, and (3) having an intention to migrate) and community participation. We find that those who experienced losses from the 2004 tsunami are more likely to participate in community activities and respond to earthquake hazards. Compared to men, women are more likely to prepare emergency kits and/or have an emergency plan and have a greater intention to migrate. Living in a community with a higher proportion of women with tertiary education increases the probability of engaging in community activities and carrying out disaster risk reduction measures. Individuals who participate in village-based activities are 5.2% more likely to undertake all three risk reduction actions compared to those not engaging in community activities. This implies that encouraging participation in community activities can have positive externalities in disaster mitigation. PMID- 26153892 TI - Detection of Hereditary 1,25-Hydroxyvitamin D-Resistant Rickets Caused by Uniparental Disomy of Chromosome 12 Using Genome-Wide Single Nucleotide Polymorphism Array. AB - CONTEXT: Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is an autosomal recessive disease caused by biallelic mutations in the vitamin D receptor (VDR) gene. No patients have been reported with uniparental disomy (UPD). OBJECTIVE: Using genome-wide single nucleotide polymorphism (SNP) array to confirm whether HVDRR was caused by UPD of chromosome 12. MATERIALS AND METHODS: A 2-year-old girl with alopecia and short stature and without any family history of consanguinity was diagnosed with HVDRR by typical laboratory data findings and clinical features of rickets. Sequence analysis of VDR was performed, and the origin of the homozygous mutation was investigated by target SNP sequencing, short tandem repeat analysis, and genome-wide SNP array. RESULTS: The patient had a homozygous p.Arg73Ter nonsense mutation. Her mother was heterozygous for the mutation, but her father was negative. We excluded gross deletion of the father's allele or paternal discordance. Genome-wide SNP array of the family (the patient and her parents) showed complete maternal isodisomy of chromosome 12. She was successfully treated with high-dose oral calcium. CONCLUSIONS: This is the first report of HVDRR caused by UPD, and the third case of complete UPD of chromosome 12, in the published literature. Genome-wide SNP array was useful for detecting isodisomy and the parental origin of the allele. Comprehensive examination of the homozygous state is essential for accurate genetic counseling of recurrence risk and appropriate monitoring for other chromosome 12 related disorders. Furthermore, oral calcium therapy was effective as an initial treatment for rickets in this instance. PMID- 26153893 TI - A Community Based Systems Diagram of Obesity Causes. AB - INTRODUCTION: Application of system thinking to the development, implementation and evaluation of childhood obesity prevention efforts represents the cutting edge of community-based prevention. We report on an approach to developing a system oriented community perspective on the causes of obesity. METHODS: Group model building sessions were conducted in a rural Australian community to address increasing childhood obesity. Stakeholders (n = 12) built a community model that progressed from connection circles to causal loop diagrams using scripts from the system dynamics literature. Participants began this work in identifying change over time in causes and effects of childhood obesity within their community. The initial causal loop diagram was then reviewed and elaborated by 50 community leaders over a full day session. RESULTS: The process created a causal loop diagram representing community perceptions of determinants and causes of obesity. The causal loop diagram can be broken down into four separate domains; social influences; fast food and junk food; participation in sport; and general physical activity. DISCUSSION: This causal loop diagram can provide the basis for community led planning of a prevention response that engages with multiple levels of existing settings and systems. PMID- 26153894 TI - Sohlh2 inhibits human ovarian cancer cell invasion and metastasis by transcriptional inactivation of MMP9. AB - Identifying key mediators of cancer invasion and metastasis is crucial to the development of new and more effective therapies. We previously identified Sohlh2 as an important inhibitor of ovarian cancer cell proliferation. However, the function of Sohlh2 in cell migration and invasion remains unknown. In this paper, we report a novel Sohlh2 to MMP9 signaling pathway in the invasive ovarian cancer. Using immunohistochemistry staining, we revealed Sohlh2 expression was inversely correlated with the invasive human ovarian cancers. In vitro experiments, forced expression of Sohlh2 led to a significant reduction in cancer cell migration and invasion. Conversely, silencing of Sohlh2 enhanced ovarian cancer cell migration and invasion. Experiments using nude mice demonstrated that the ectopic Sohlh2 expression inhibited the HO8910 cell capability of the metastasis to the lungs and livers. Ectopic overexpression of Sohlh2 in the invasive HO8910 cells reduced the MMP9 expression, whereas Sohlh2 knockdown from the non-invasive, SKOV3 cells increased the MMP9 expression. Promoter activation and binding analyses indicated that Sohlh2 repressed the MMP9 expression by directly acting on the MMP9 gene promoter. Inhibition of MMP9 dramatically blocked the Sohlh2 knockdown-enhanced SKOV3 cell invasion, and ectopic expression of MMP9 compensated for the anti-invasive activity of Sohlh2 in HO8910 cells. Overall, these results demonstrate for the first time that Sohlh2 functions as a tumor metastasis suppressor. Modulation of Sohlh2 expression has the potential to be a target for cancer therapy. (c) 2015 Wiley Periodicals, Inc. PMID- 26153896 TI - Normal Organ Weights in Women: Part I-The Heart. AB - Cardiac enlargement is a well-known independent risk factor for sudden cardiac death, though the definition of what constitutes cardiac enlargement is not universally established. A previous study was undertaken to establish a normal range for male hearts to address this issue; the present study was designed to address the issue and to determine normal cardiac weights in adult human females. A prospective study was undertaken of healthy females dying from sudden, traumatic deaths aged 18 to 35 years. Cases were excluded if: there was a history of medical illness, including illicit drug use; prolonged medical treatment was performed; there was a prolonged period between the time of injury and death; body length and weight could not be accurately assessed; if there was significant cardiac injury; or if any illness or intoxication was identified after gross, microscopic, and toxicologic analysis, including evidence of systemic disease. A total of 102 cases met criteria for inclusion in the study during the approximately 10-year period of data collection from 2004 to 2014. The decedents had an average age of 24.4 years and ranged in length from 141 to 182 cm (56.4 to 72.8 in.) with an average length of 160 cm (64 in.). The weight ranged from 35.9 to 152 kg (79 to 334 lbs) with an average weight of 65.3 kg (143 lbs). The majority of the decedents (86%) died from either ballistic or blunt force (including craniocerebral) injuries. Overall, the heart weights ranged from 156 to 422 g with an average of 245 g and a standard deviation of 52 g. Regression analysis was performed to assess the relationship between heart weight and body weight, body length, and body mass index, respectively, and found insufficient associations to enable predictability. The authors, therefore, propose establishing a normal range for heart weight in women of 148 to 296 g. PMID- 26153895 TI - Bio-imaging and Photodynamic Therapy with Tetra Sulphonatophenyl Porphyrin (TSPP) TiO2 Nanowhiskers: New Approaches in Rheumatoid Arthritis Theranostics. AB - Since Rheumatoid arthritis (RA) is one of the major human joint diseases with unknown etiology, the early diagnosis and treatment of RA remains a challenge. In this contribution we have explored the possibility to utilize novel nanocomposites of tetera suplhonatophenyl porphyrin (TSPP) with titanium dioxide (TiO2) nanowhiskers (TP) as effective bio-imaging and photodynamic therapeutic (PDT) agent for RA theranostics. Our observations demonstrate that TP solution PDT have an ameliorating effect on the RA by decreasing significantly the IL-17 and TNF-alpha level in blood serum and fluorescent imaging could enable us to diagnose the disease in subclinical stages and bio-mark the RA insulted joint. PMID- 26153897 TI - Erythrocyte Membrane-Enveloped Polymeric Nanoparticles as Nanovaccine for Induction of Antitumor Immunity against Melanoma. AB - Cancer immunotherapy is mainly focused on manipulating patient's own immune system to recognize and destroy cancer cells. Vaccine formulations based on nanotechnology have been developed to target delivery antigens to antigen presenting cells (APCs), especially dendritic cells (DCs) for efficiently induction of antigen-specific T cells response. To enhance DC targeting and antigen presenting efficiency, we developed erythrocyte membrane-enveloped poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for antigenic peptide (hgp10025-33) and toll-like receptor 4 agonist, monophosphoryl lipid (MPLA). A Mannose-inserted membrane structure was constructed to actively target APCs in the lymphatic organ, and redox-sensitive peptide-conjugated PLGA nanoparticles were fabricated which prone to cleave in the intracellular milieu. The nanovaccine demonstrated the retained protein content in erythrocyte and enhanced in vitro cell uptake. An antigen-depot effect was observed in the administration site with promoted retention in draining lymph nodes. Compared with other formulations after intradermal injection, the nanovaccine prolonged tumor occurring time, inhibited tumor growth, and suppressed tumor metastasis in prophylactic, therapeutic, and metastatic melanoma models, respectively. Additionally, we revealed that nanovaccine effectively enhanced IFN-gamma secretion and CD8(+) T cell response. Taken together, these results demonstrated the great potential in applying an erythrocyte membrane-enveloped polymeric nanoplatform for an antigen delivery system in cancer immunotherapy. PMID- 26153899 TI - Stable Stoichiometry of Gas-Phase Manganese Oxide Cluster Ions Revealed by Temperature-Programmed Desorption. AB - Temperature-programmed desorption (TPD) experiments were performed on gas-phase manganese oxide cluster ions, namely, Mn(n)O(m)(+) (n = 3-20) and Mn(n)O(m)(-) (n = 3-18). These cluster ions were prepared by laser ablation of a manganese rod in the presence of oxygen gas, and their composition was investigated using mass spectrometry. The composition of Mn(n)O(m)(+/-) distribution lies above the m = (4/3)n line. When the cluster ions were heated to 1000 K, Mn(n)O(m)(+) (m = (4/3)n + delta, with delta = -1, 0) and Mn(n)O(m)(-) (m = (4/3)n + delta, with delta = 0, 1) was found to be the predominant species, formed by thermal dissociation. These experimental findings indicate that the nascent manganese oxide clusters comprise robust Mn(n)O(m)(+/-) (m/n ~ 4/3) and weakly bound excess oxygen atoms. On the basis of the TPD experiments, the oxygen-molecule release was identified as the main dissociation channel. The temperature dependence of O2 desorption was found to be similar among the clusters with the same oxygen excess or deficiency regardless of the number of Mn atoms. The threshold energy of O2 desorption was estimated for Mn4O(m)(+) (m = 6-11) and compared with bond dissociation energies calculated by density functional theory. PMID- 26153898 TI - Licensing by Inflammatory Cytokines Abolishes Heterogeneity of Immunosuppressive Function of Mesenchymal Stem Cell Population. AB - When mesenchymal stem cells (MSCs) are used for therapy of immunological pathologies, they get into an inflammatory environment, altering the effectiveness of the treatment. To establish the impact of environmental inflammatory factors on MSCs' immunofunction in the mirror of intrinsic heterogeneity of mouse MSC population, individual MSC clones were generated and characterized. Adipogenic but not osteogenic differentiation and pro-angiogenic activity of five independent MSC cell lines were similar. Regarding osteogenic differentiation, clones MSC3 and MSC6 exhibited poorer capacity than MSC2, MSC4, and MSC5. To study the immunosuppressive heterogeneity, in vitro and in vivo experiments have been carried out using T-cell proliferation assay and delayed type hypersensitivity (DTH) response, respectively. A remarkable difference was found between the clones in their ability to inhibit T-cell proliferation in the following order: MSC2>=MSC5>MSC4>MSC3 >> MSC6. Nevertheless, the differences between the immunosuppressive activities of the individual clones disappeared on pretreatment of the cells with pro-inflammatory cytokines, a procedure called licensing. Stimulation of all clones with IFN-gamma and TNF-alpha resulted in elevation of their inhibitory capability to a similar level. Nitric oxide (NO) and prostaglandin E2 (PGE2) were identified as major mediators of immunofunction of the MSC clones. The earlier findings were also supported by in vivo results. Without licensing, MSC2 inhibited DTH response, while MSC6 did not affect DTH response. In contrast, prestimulation of MSC6 with inflammatory cytokines resulted in strong suppression by this clone as well. Here, we have showed that MSC population is functionally heterogeneous in terms of immunosuppressive function; however, this variability is largely reduced under pro-inflammatory conditions. PMID- 26153900 TI - Adsorption-induced conformational isomerization of alkyl-substituted thiophene oligomers on Au(111): impact on the interfacial electronic structure. AB - Alkyl-substituted quaterthiophenes on Au(111) form dimers linked by their alkyl substituents and, instead of adopting the trans conformation found in bulk oligothiophene crystals, assume cis conformations. Surprisingly, the impact of the conformation is not decisive in determining the lowest unoccupied molecular orbital energy. Scanning tunneling microscopy and spectroscopy of the adsorption geometries and electronic structures of alkyl-substituted quaterthiophenes show that the orbital energies vary substantially because of local variations in the Au(111) surface reactivity. These results demonstrate that interfacial oligothiophene conformations and electronic structures may differ substantially from those expected based on the band structures of bulk oligothiophene crystals. PMID- 26153901 TI - Early Intervention and AAC: What a Difference 30 Years Makes. AB - This article provides an overview of early intervention and AAC over the 30-year period since the founding of the journal Augmentative and Alternative Communication in 1985. It discusses the global context for early intervention and addresses issues pertaining to young children from birth to 6 years of age. It provides a narrative review and synthesis of the evidence base in AAC and early intervention. Finally, it provides implications for practice and future research directions. PMID- 26153902 TI - Low-dose CT screening using hybrid iterative reconstruction: confidence ratings of diagnoses of simulated lesions other than lung cancer. AB - OBJECTIVE: To evaluate the confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose screening CT with hybrid iterative reconstruction (IR). METHODS: Simulated lesions (emphysema, mediastinal masses and interstitial pneumonia) in a chest phantom were scanned by a 320-row area detector CT. The scans were performed by 64-row and 160-row helical scans at various dose levels and were reconstructed by filtered back projection (FBP) and IR. Emphysema, honeycombing and reticular opacity were visually scored on a four point scale by six thoracic radiologists. The ground-glass opacity as a percentage of total lung volume (%GGO), CT value and contrast-to-noise ratio (CNR) of mediastinal masses were calculated. These scores and values were compared between FBP and IR. Wilcoxon's signed-rank test was used (p < 0.05). Interobserver agreements were evaluated by kappa statistics. RESULTS: There were no significant differences in visual assessment. Interobserver agreement was almost perfect. CT values were almost equivalent between FBP and IR, whereas CNR with IR was significantly higher than that with FBP. %GGO significantly increased at low-dose levels with FBP; however, IR suppressed the elevation. CONCLUSION: The confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose CT screening were not degraded with hybrid IR compared with FBP. ADVANCES IN KNOWLEDGE: Hybrid IR did not degrade the confidence ratings of diagnoses on visual assessment and differential diagnoses based on CT value of mediastinal masses, and it showed the advantage of higher GGO conspicuity at low dose level. Radiologists can analyse images of hybrid IR alone on low-dose CT screening for lung cancer. PMID- 26153903 TI - Axillary irradiation omitting axillary dissection in breast cancer: is there a role for shoulder-sparing proton therapy? AB - The recent EORTC 10981-22023 AMAROS trial showed that axillary radiotherapy and axillary lymph node dissection provide comparable local control and reduced lymphoedema in the irradiated group. However, no significant differences between the two groups in range of motion and quality of life were reported. It has been acknowledged that axillary irradiation could have induced some toxicity, particularly shoulder function impairment. In fact, conventional breast irradiation by tangential beams has to be modified to achieve full-dose coverage of the axillary nodes, including in the treatment field a larger portion of the shoulder structures. In this scenario, alternative irradiation techniques were discussed. Compared with modern photon techniques, axillary irradiation by proton therapy has the potential for sparing the shoulder without detrimental increase of the medium-to-low doses to the other normal tissues. PMID- 26153904 TI - Thermoresponsive Polymer Micelles as Potential Nanosized Cancerostatics. AB - An effective chemotherapy for neoplastic diseases requires the use of drugs that can reach the site of action at a therapeutically efficacious concentration and maintain it at a constant level over a sufficient period of time with minimal side effects. Currently, conjugates of high-molecular-weight hydrophilic polymers or biocompatible nanoparticles with stimuli-releasable anticancer drugs are considered to be some of the most promising systems capable of fulfilling these criteria. In this work, conjugates of thermoresponsive diblock copolymers with the covalently bound cancerostatic drug pirarubicin (PIR) were synthesized as a reversible micelle-forming drug delivery system combining the benefits of the above-mentioned carriers. The diblock copolymer carriers were composed of hydrophilic poly[N-(2-hydroxypropyl)methacrylamide]-based block containing a small amount (~ 5 mol %) of comonomer units with reactive hydrazide groups and a thermoresponsive poly[2-(2-methoxyethoxy)ethyl methacrylate] block. PIR was attached to the hydrophilic block of the copolymer through the pH-sensitive hydrazone bond designed to be stable in the bloodstream at pH 7.4 but to be degraded in an intratumoral/intracellular environment at pH 5-6. The temperature induced conformation change of the thermoresponsive block (coil-globule transition), followed by self-assembly of the copolymer into a micellar structure, was controlled by the thermoresponsive block length and PIR content. The cytotoxicity and intracellular transport of the conjugates as well as the release of PIR from the conjugates inside the cells, followed by its accumulation in the cell nuclei, were evaluated in vitro using human colon adenocarcinoma (DLD 1) cell lines. It was demonstrated that the studied conjugates have a great potential to become efficacious in vivo pharmaceuticals. PMID- 26153909 TI - Measles, Mumps, and Rubella Serostatus and Response to MMR Vaccination Among HIV Infected Adults. PMID- 26153910 TI - Norepinephrine-induced myeloid-derived suppressor cells block T-cell responses via generation of reactive oxygen species. AB - Increased numbers of myeloid-derived suppressor cells (MDSCs) are often observed in various pathological and physiological conditions. However, the interactions between neurotransmitters and MDSCs have not been elucidated. In this study, we studied whether norepinephrine (NE), a neurotransmitter, could affect the differentiation of human MDSCs in vitro. Flow cytometric analysis showed that treatment with 20 MUM NE significantly enhanced the expansion of MDSCs. The NE generated MDSCs suppressed the T-cells proliferation, depending on the production of reactive oxygen species (ROS). Moreover, the expansion of MDSCs induced by NE resulted in a dramatic induction of nicotinamide adenine dinucleotide phosphate oxidase subunit P47(phox). Addition of the ROS inhibitor catalase into the MDSCs/T-cell co-culture system partly abrogated the suppressive effects of MDSCs on T-cell proliferation. In summary, our data have shown that NE enhanced the expansion of human MDSCs in vitro, providing important insights into the novel roles of neurotransmitters in the regulation of myeloid cell differentiation and function. PMID- 26153911 TI - 17beta-Estradiol transcriptionally modulates Nlrp1 and Nlrp3 inflammasomes in gonadectomized rats with inflammation. AB - CONTEXT: It has been reported that 17beta-estradiol (E2) reduces the expression of inflammatory molecules, but there are no data that show the effect of E2 on the transcriptional regulation of innate immunity-related molecules and inflammasomes. OBJECTIVE: To study the effect of 17beta-estradiol (E2) on the transcriptional expression of the NLR family, pyrin domain containing 1 (Nlrp1) and (Nlrp3) inflammasomes, which are mediators of inflammation. MATERIALS AND METHODS: Inflammation was induced in adult female gonadectomized (Gdx) rats by intramuscular injection of complete Freund's adjuvant (CFA). Measurements were taken at different times after the treatment. Gene expression determinations were done by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: CFA induced inflammation increased the transcription of Nlrp3, IL-1beta (p < 0.05), vascular cell adhesion molecule 1 (VCAM1), E-selectin and estrogen receptor 1 alpha (ERalpha) (p < 0.001) and decreased the transcription of Nlrp1, Caspase-1, IL-33, NFKB1, ICAM1, ICAM2, GCRalpha, GCRbeta, UCP3 and PGC1alpha (p < 0.001) compared to the control. The administration of E2 to the inflamed tissue significantly increased the expression of Nlrp1, NFKB1, ERalpha, UCP3, Caspase-1, E-selectin (p < 0.001), IL-18 and ERalpha (p < 0.05) and decreased IL-1beta and VCAM1 (p < 0.005) compared to the control. DISCUSSION AND CONCLUSION: CFA differentially modulates the transcription of inflammasome-related genes and the administration of E2 increases the expression of ERalpha and Nlrp1 together with NFKB1, a key molecule in the activation of the inflammasomes. Finally, an analysis using the web interface GeneMANIA revealed an interaction between several genes, indicating a functional correlation in this model. PMID- 26153913 TI - Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies. AB - Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of the study was to systematically review the literature and critically answer the question: In patients with HS, do cardiovascular risk factors appear at a significantly higher rate compared with controls? The main search was conducted in Medline, Embase and the Cochrane Central Register. Studies eligible for inclusion were of case-control, cross-sectional and cohort design, and included comparison of any cardiovascular risk factor(s) in patients with HS with those of control groups. An I(2) value > 50% was considered to show substantial heterogeneity. In this case, DerSimonian and Laird random-effect models were considered to compute pooled odds ratios (OR). Otherwise, a fixed effects model was suitable. Nine studies, with 6174 patients with HS and 24 993 controls, were included. Significant association of HS with obesity [OR 3.45, 95% confidence interval (CI) 2.20-5.38, P < 0.001], central obesity (OR 2.97, 95% CI 1.41-6.25, P = 0.004), active smoking (OR 4.34, 95% CI 2.48-7.60, P < 0.001), history of smoking (OR 6.34, 95% CI 2.41-16.68, P < 0.001), hypertriglyceridemia (OR 1.67, 95% CI 1.14-2.47, P = 0.009), low high-density lipoprotein (HDL) (OR 2.48, 95% CI 1.49-4.16, P < 0.001), diabetes (OR 2.85, 95% CI 1.34-6.08, P = 0.007) and metabolic syndrome (OR 2.22, 95% CI 1.62-3.06, P < 0.001) was detected. Associations were significant both in population and hospital patients with HS, with hospital HS groups having uniformly higher ORs than the population HS groups. Causality could not be assessed. Heterogeneity was substantial in all analyses. This systematic review indicated that cardiovascular risk factors appear at a significantly higher rate in patients with HS compared with controls. The need for screening of patients with HS for modifiable cardiovascular risks is emphasized. PMID- 26153914 TI - Factors Affecting Pathogen Survival in Finished Dairy Compost with Different Particle Sizes Under Greenhouse Conditions. AB - This study investigated the survival of Escherichia coli O157:H7 and Salmonella Typhimurium in finished dairy compost with different particle sizes during storage as affected by moisture content and temperature under greenhouse conditions. The mixture of E. coli O157:H7 and S. Typhimurium strains was inoculated into the finished composts with moisture contents of 20, 30, and 40%, separately. The finished compost samples were then sieved into 3 different particle sizes (>1000, 500-1000, and <500 MUm) and stored under greenhouse conditions. For compost samples with moisture contents of 20 and 30%, the average Salmonella reductions in compost samples with particle sizes of >1000, 500-1000, and <500 MUm were 2.15, 2.27, and 2.47 log colony-forming units (CFU) g(-1) within 5 days of storage in summer, respectively, as compared with 1.60, 2.03, and 2.26 log CFU g(-1) in late fall, respectively, and 2.61, 3.33, and 3.67 log CFU g(-1) in winter, respectively. The average E. coli O157:H7 reductions in compost samples with particle sizes of >1000, 500-1000, and <500 MUm were 1.98, 2.30, and 2.54 log CFU g(-1) within 5 days of storage in summer, respectively, as compared with 1.70, 2.56, and 2.90 log CFU g(-1) in winter, respectively. Our results revealed that both Salmonella and E. coli O157:H7 in compost samples with larger particle size survived better than those with smaller particle sizes, and the initial rapid moisture loss in compost may contribute to the fast inactivation of pathogens in the finished compost. For the same season, the pathogens in the compost samples with the same particle size survived much better at the initial moisture content of 20% compared to 40%. PMID- 26153915 TI - Eggshell and Histology Provide Insight on the Life History of a Pterosaur with Two Functional Ovaries. AB - The counterpart of a previously described non-pterodactyloid pterosaur with an egg revealed the presence of a second egg inside the body cavity of this gravid female. It clearly shows that pterosaurs had two functional oviducts and demonstrates that the reduction of one oviduct was not a prerequisite for developing powered flight, at least in this group. Compositional analysis of one egg suggests the lack of a hard external layer of calcium carbonate. Histological sections of one femur lack medullary bone and further demonstrate that this pterosaur reached reproductive maturity before skeletal maturity. This study shows that pterosaurs laid eggs even smaller than previously thought and had a reproductive strategy more similar to basal reptiles than to birds. Whether pterosaurs were highly precocial or needed parental care is still open to debate. PMID- 26153916 TI - Mass Spectrometric and Spectrophotometric Analyses Reveal an Alternative Structure and a New Formation Mechanism for Melanin. AB - In this study, we investigated the formation mechanism and chemical structure of melanin that results from the self-assembly of L-3,4-dihydroxyphenylalanine (L DOPA). Using a combination of "top-down" and "bottom-up" approaches, and on the basis of state-of-the-art electrospray ionization mass spectrometry (ESI-MS) results, we propose a new formation mechanism and an alternative structure for melanin. Specifically, our study of the self-aggregation of L-DOPA based on L DOPA clusters revealed that melanin is comprised partially of noncovalent supramolecular aggregate that is formed by self-aggregation of L-DOPA and with the individual monomers linked together by a combination of hydrogen bonds, pi-pi stacking, and ionic bonds. Furthermore, our study showed that unmodified L-DOPA may be part of the building block for melanin in addition to the previously proposed indole derivative based on L-DOPA cyclization. A similar self aggregation phenomenon was also observed in other structurally related catecholamines, for example, adrenaline. PMID- 26153917 TI - Reactivity of Imidazole Derivatives toward Phosphate Triester in DMSO/Water Mixtures: A Comprehensive Study on the Solvent Effect. AB - Many imidazole (IMZ) derivatives of pharmaceutical interest, which are potentially catalytic in dephosphorylation reactions, are soluble solely in mixtures of water and organic solvent. In order to understand these poorly explored reactions and properly compare them, a thorough study related to solvent effects for the analogous spontaneous reaction and with common IMZ derivatives is necessary, which is lacking in the literature. Herein, we report a quantitative solvent effect analysis in DMSO/water mixtures for (i) the hydrolysis reaction of diethyl 2,4-dinitrophenylphosphate (DEDNPP) and (ii) the nucleophilic reaction of IMZ and 1-methylimidazole (MEI) with DEDNPP. The solvent effect was fitted satisfactorily with multiple regression analysis, correlating the obtained second order rate constants with solvent parameters such as acidity, basicity, and polarity/polarizability from Catalan's scale. The contribution of these parameters can be taken into account to elucidate the reactivity in these media. Interestingly, IMZ is more reactive than MEI in DMSO, compared to water alone, which is attributed to the availability of hydrogen-bond formation. Nuclear magnetic resonance spectroscopy ((1)H, (13)C, and (31)P), mass spectrometry, thermodynamic analysis, and density functional theory calculations were carried out to corroborate the proposed nucleophilic mechanism. PMID- 26153918 TI - Laparoscopic Partial Nephrectomy with Precise Segmental Renal Artery Clamping for Clinical T1b Tumors. AB - OBJECTIVE: To assess the technique and short-term outcomes of laparoscopic partial nephrectomy (LPN) with precise segmental renal artery clamping for clinical T1b (cT1b) tumors and to analyze the possible factors affecting the glomerular filtration rate (GFR) reduction. MATERIALS AND METHODS: This retrospective study investigated the outcomes of 72 patients with cT1b tumors who received LPN from June 2008 to May 2014. Based on three-dimensional dynamic renal vascular models built before surgery, target arteries were precisely clamped and tumors were removed under regional parenchymal ischemia. Perioperative and follow up outcomes were analyzed. RESULTS: All the LPN procedures were effectively performed using the novel technique, without converting to main renal artery clamping or open surgery. The mean operative time was 86 min, with a mean warm ischemic time of 25 min. The median estimated blood loss was 200 mL (range: 80 800). The postoperative mean GFR was 64% of the preoperative baseline, and the total complication rate was 19.4%. In multivariable analyses, the two independent factors affecting postoperative GFR were the RENAL nephrometry score (RNS) and number of intraoperative clamped segmental arteries. The median follow-up was 24 months (range: 6-72). The overall, recurrence-free, and cancer-specific survival rates were 100%, 95.8%, and 100%, respectively. CONCLUSIONS: For patients with cT1b tumor, LPN with precise segmental renal artery clamping is safe and feasible for removing tumors and preserving the blood supply and normal renal parenchyma. Short-term oncologic and functional outcomes were satisfactory. Postoperative GFR was related to the preoperative RNS and number of intraoperative clamped segmental arteries. PMID- 26153919 TI - Electron Transfer through Surface-Grown, Ferrocene-Capped Oligophenylene Molecular Wires (5-50 A) on n-Si(111) Photoelectrodes. AB - We report the surface growth of oligophenylene molecular wires on Si(111) substrates and their electron-transfer (ET) properties. Iterative wire growth of biphenylene was achieved via Pd-catalyzed Negishi reactions for lengths of nphenyl = 1, 2, 4, 6, 8, and 12 (d ~ 5-50 A). The triflato-capped wires were functionalized with vinylferrocene for potentiometric studies. For the oligophenylenes of nphenyl = 1, 2, and 4 (wire length d ~ 5-20 A), there was a strong distance dependence (kapp = 22.6, 16.0, 8.40 s(-1), respectively), correlated to beta = 0.07 A(-1). In contrast, longer oligophenylenes for nphenyl = 4-12 (d ~ 20-50 A) displayed a negligible distance dependence with an ET rate of kapp ~ 10.0 +/- 1.6 s(-1). These data suggest a distance-dependent tunneling mechanism at short lengths (d < 20 A) and a distance-independent ET at longer lengths (d > 20 A). PMID- 26153921 TI - Abuse Deterrent Formulations of Prescription Opioids--Reply. PMID- 26153922 TI - Orbital characters and electronic correlations in KCo2Se2. AB - We report a comprehensive study of the tridimensional nature and orbital characters of the low-energy electronic structure in KCo2Se2, using polarization- and photon energy-dependent angle-resolved photoemission spectroscopy. We observed one electron-like Fermi surface (FS) at the Brillouin zone (BZ) center, four electron-like FSs centered at the BZ corner, and one hole-like FS at the BZ boundary. The FSs show weak dispersion along the kz direction, indicating the near-two-dimensional nature of FSs in KCo2Se2. In combination with the local density approximation calculations, we determined the orbital characters of the low-energy electronic bands, which are mainly derived from the Co 3d orbital, mixed with part of the Se 4p states. The [Formula: see text] orbital gives a significant contribution to the band crossing the Fermi level. A band renormalization of about 1.6 is needed to capture the essential dispersive features, which suggests that electronic correlations are much weaker than that in KyFe2-xSe2. PMID- 26153920 TI - Functional abnormalities in iPSC-derived cardiomyocytes generated from CPVT1 and CPVT2 patients carrying ryanodine or calsequestrin mutations. AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by syncope and sudden death occurring during exercise or acute emotion. CPVT is caused by abnormal intracellular Ca(2+) handling resulting from mutations in the RyR2 or CASQ2 genes. Because CASQ2 and RyR2 are involved in different aspects of the excitation-contraction coupling process, we hypothesized that these mutations are associated with different functional and intracellular Ca(2+) abnormalities. To test the hypothesis we generated induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CM) from CPVT1 and CPVT2 patients carrying the RyR2(R420Q) and CASQ2(D307H) mutations, respectively, and investigated in CPVT1 and CPVT2 iPSC-CM (compared to control): (i) The ultrastructural features; (ii) the effects of isoproterenol, caffeine and ryanodine on the [Ca(2+) ]i transient characteristics. Our major findings were: (i) Ultrastructurally, CASQ2 and RyR2 mutated cardiomyocytes were less developed than control cardiomyocytes. (ii) While in control iPSC-CM isoproterenol caused positive inotropic and lusitropic effects, in the mutated cardiomyocytes isoproterenol was either ineffective, caused arrhythmias, or markedly increased diastolic [Ca(2+) ]i . Importantly, positive inotropic and lusitropic effects were not induced in mutated cardiomyocytes. (iii) The effects of caffeine and ryanodine in mutated cardiomyocytes differed from control cardiomyocytes. Our results show that iPSC CM are useful for investigating the similarities/differences in the pathophysiological consequences of RyR2 versus CASQ2 mutations underlying CPVT1 and CPVT2 syndromes. PMID- 26153923 TI - Rates of Hydroxyl Radical Production from Transition Metals and Quinones in a Surrogate Lung Fluid. AB - Hydroxyl radical ((*)OH) is the most reactive, and perhaps most detrimental to health, of the reactive oxygen species. (*)OH production in lungs following inhalation of particulate matter (PM) can result from redox-active chemicals, including iron and copper, but the relative importance of these species is unknown. This work investigates (*)OH production from iron, copper, and quinones, both individually and in mixtures at atmospherically relevant concentrations. Iron, copper, and three of the four quinones (1,2-naphthoquinone, phenanthrenequinone and 1,4-naphthoquinone) produce (*)OH. Mixtures of copper or quinones with iron synergistically produce (*)OH at a rate 20-130% higher than the sum of the rates of the individual redox-active species. We developed a regression equation from 20 mixtures to predict the rate of (*)OH production from the particle composition. For typical PM compositions, iron and copper account for most (*)OH production, whereas quinones are a minor source, although they can contribute if present at very high concentrations. This work shows that Cu contributes significantly to (*)OH production in ambient PM; other work has shown that Cu appears to be the primary driver of HOOH production and dithiothreitol (DTT) loss in ambient PM extracts. Taken together, these results indicate that copper appears to be the most important individual contributor to direct oxidant production from inhaled PM. PMID- 26153925 TI - Tuition fees and loans won't bring in recruits. PMID- 26153924 TI - A mitochondrial analysis reveals distinct founder effect signatures in Canarian and Balearic goats. AB - In the course of human migrations, domestic animals often have been translocated to islands with the aim of assuring food availability. These founder events are expected to leave a genetic footprint that may be recognised nowadays. Herewith, we have examined the mitochondrial diversity of goat populations living in the Canarian and Balearic archipelagos. Median-joining network analysis produced very distinct network topologies for these two populations. Indeed, a majority of Canarian goats shared a single ancestral haplotype that segregated in all sampled islands, suggesting a single founder effect followed by a stepping-stone pattern of diffusion. This haplotype also was present in samples collected from archaeological assemblies at Gran Canaria and Lanzarote, making evident its widespread distribution in ancient times. In stark contrast, goats from Majorca and Ibiza did not share any mitochondrial haplotypes, indicating the occurrence of two independent founder events. Furthermore, in Majorcan goats, we detected the segregation of the mitochondrial G haplogroup that has only been identified in goats from Egypt, Iran and Turkey. This finding suggests the translocation of Asian and/or African goats to Majorca, possibly as a consequence of the Phoenician and Carthaginian colonisations of this island. PMID- 26153926 TI - Scrap nursing bursaries and bring in tuition fees, say universities. PMID- 26153927 TI - Ghana delegation and the RCN swap notes on pay and staffing. PMID- 26153928 TI - Employers issue post-Savile advice on official visits. PMID- 26153929 TI - Short-sighted cuts to public health budgets will cost NHS dear, says RCN. PMID- 26153930 TI - Inspectors heap praise on nurse-led GP practice. PMID- 26153931 TI - Deficits warning - last year was tough but this year will be tougher. PMID- 26153932 TI - A hub of information on diabetes. PMID- 26153933 TI - Use finger pricking to cut prescriptions. PMID- 26153934 TI - Invest more in hospital care of the most vulnerable children. PMID- 26153936 TI - Red armband for care team captain. PMID- 26153937 TI - Nurses slate mental health staffing guide for not setting specific levels. PMID- 26153938 TI - Why the odds feel stacked against nurse recruiters outside the NHS. PMID- 26153944 TI - Personality disorders. PMID- 26153945 TI - Diabetes care tool puts kids in control. AB - The nursing team in the children's diabetes service at Pennine Care NHS Foundation Trust has developed an app and website to help children and young people with type 1 diabetes manage the condition. The initiative focuses on using social media to increase peer support. The team were runners up in the 2015 Nursing Standard Excellence in Diabetes Specialist Nursing Award, sponsored by Sanofi Diabetes. PMID- 26153946 TI - Why should I have to use a catheter? AB - The No Catheter - No CAUTI campaign urges all clinicians to keep catheter use to a minimum and ensure that when they are used, they are used properly. Supporters want a revolution in awareness, putting catheters and associated infections on the same level as, for example, handwashing and drip-line infections. PMID- 26153947 TI - Taking the plunge with lipoedema. AB - Women wait decades for an accurate diagnosis of lipoedema. Earlier diagnosis is essential to prevent the condition progressing to lymphoedema, with its risk of life-threatening cellulitis. PMID- 26153960 TI - England's CNO has shown courage and leadership. PMID- 26153961 TI - The 'noise' surrounding nurse staffing will not diminish. PMID- 26153962 TI - Safe staffing guidance is too important to be sidelined. PMID- 26153963 TI - Planning a seven-day-a-week NHS without extra funding is madness. PMID- 26153964 TI - Incident reporting should be used as a catalyst for change. PMID- 26153965 TI - Congress was empowering and revived my passion for nursing. PMID- 26153969 TI - Using observational methods in nursing research. AB - Observation is a research data-collection method used generally to capture the activities of participants as well as when and where things are happening in a given setting. It checks description of the phenomena against what the researcher perceives to be fact in a rich experiential context. The method's main strength is that it provides direct access to the social phenomena under consideration. It can be used quantitatively or qualitatively, depending on the research question. Challenges in using observation relate to adopting the role of participant or non participant researcher as observer. This article discusses some of the complexities involved when nurse researchers seek to collect observational data on social processes in naturalistic settings using unstructured or structured observational methods in qualitative research methodology. A glossary of research terms is provided. PMID- 26153970 TI - Medical treatment and management of patients with dementia. AB - This article, the fifth in a series on dementia, discusses the principles of management and treatment of people with dementia. It describes how to proceed after a diagnosis of dementia has been made in the early stages of the condition, and general measures to maintain physical and mental health. Drug therapy for cognitive dysfunction is explained in the context of the National Institute for Health and Care Excellence guidance, and strategies for managing depression and psychotic symptoms are outlined. Non-pharmacological approaches are often effective. For behavioural problems such as agitation and aggression, it is important to try to understand any underlying factors. In general, the most important strategy is to avoid excessive prescribing. PMID- 26153971 TI - Clinical presentation, assessment and management of pre-eclampsia. AB - Pre-eclampsia is a complex and unpredictable disorder that may occur during pregnancy. Its presentation ranges from mild to severe, and the condition may lead to the death of the mother and/or the baby in extreme cases. The earlier the disorder is detected and managed, the better the outcome. This article provides an outline of the disorder and its management, within the framework of UK and international guidelines. A series of suggested activities encourages the reader to reflect on the information provided within the context of their practice. PMID- 26153972 TI - Presentation skills. PMID- 26153973 TI - All in my day's work. PMID- 26153974 TI - Racing back to hospital practice. PMID- 26153976 TI - Focus on offenders' health. PMID- 26153977 TI - Student life - a six-week placement opened doors for me. PMID- 26153979 TI - Exciton-photon correlations in bosonic condensates of exciton-polaritons. AB - Exciton-polaritons are mixed light-matter quasiparticles. We have developed a statistical model describing stochastic exciton-photon transitions within a condensate of exciton polaritons. We show that the exciton-photon correlator depends on the rate of incoherent exciton-photon transformations in the condensate. We discuss implications of this effect for the quantum statistics of photons emitted by polariton lasers. PMID- 26153978 TI - Prevalence and Antimicrobial Resistance of Campylobacter Isolated from Dressed Beef Carcasses and Raw Milk in Tanzania. AB - Campylobacter species are commonly transmitted to humans through consumption of contaminated foods such as milk and meat. The aim of this study was to investigate the prevalence, antimicrobial resistance, and genetic determinants of resistance of Campylobacter isolated from raw milk and beef carcasses in Tanzania. The antimicrobial resistance genes tested included blaOXA-61 (ampicillin), aph-3-1 (aminoglycoside), tet(O) (tetracycline), and cmeB (multi drug efflux pump). The prevalence of Campylobacter was 9.5% in beef carcasses and 13.4% in raw milk, respectively. Using multiplex-polymerase chain reaction (PCR), we identified 58.1% of the isolates as Campylobacter jejuni, 30.7% as Campylobacter coli, and 9.7% as other Campylobacter spp. One isolate (1.6%) was positive for both C. jejuni and C. coli specific PCR. Antimicrobial susceptibility testing using the disk diffusion assay and the broth microdilution method showed resistance to: ampicillin (63% and 94.1%), ciprofloxacin (9.3% and 11.8%), erythromycin (53.7% and 70.6%), gentamicin (0% and 15.7%), streptomycin (35.2% and 84.3%), and tetracycline (18.5% and 17.7%), respectively. Resistance to azithromycin (42.6%), nalidixic acid (64.8%), and chloramphenicol (13%) was determined using the disk diffusion assay only, while resistance to tylosin (90.2%) was quantified using the broth microdilution method. The blaOXA-61 (52.6% and 28.1%), cmeB (26.3% and 31.3%), tet(O) (26.3% and 31.3%), and aph-3-1 (5.3% and 3.0%) were detected in C. coli and C. jejuni. These findings highlight the extent of antimicrobial resistance in Campylobacter occurring in important foods in Tanzania. The potential risks to consumers emphasize the need for adequate control approaches, including the prudent use of antimicrobials to minimize the spread of antimicrobial-resistant Campylobacter. PMID- 26153980 TI - DNA damage response: The spliceosome cashes in at the ATM. PMID- 26153981 TI - An instructive case of presumed brown snake (Pseudonaja spp.) envenoming. AB - CONTEXT: Several species of medically important Australian elapid snakes are frequently involved in human envenoming. The brown snake group (Pseudonaja spp., 9 species) is most commonly responsible for envenoming including life-threatening or fatal cases. Several Pseudonaja spp. can inflict human envenoming that features minor local effects, but may cause serious systemic venom disease including defibrination coagulopathy, thrombocytopenia, micro-angiopathic hemolytic anemia (MAHA) and, rarely, paralysis. Pseudonaja envenoming is typically diagnosed by history, clinical assessment including occasional active clinical bleeding noted on physical examination (e.g. from venipuncture sites, recent cuts, etc.), and laboratory detection of coagulopathy (prolonged activated partial thromboplastin time [APTT]/INR, elevated D-dimer, afibrinogenemia and thrombocytopenia). Lack of verified identity of the envenoming snake species is a common problem in Australia and elsewhere. Identification and confirmation of the envenoming Australian snake taxon is often attempted with enzyme sandwich immunoassay venom detection kits (SVDKs). However, the SVDK has limited utility due to unreliable specificity and sensitivity when used to detect venoms of some Australian elapids. Antivenom (AV) remains the cornerstone of treatment, although there is debate concerning the recommended dose (1 vs. 2 or more vials) necessary to treat serious Pseudonaja envenoming. Envenomed patients receiving timely treatment uncommonly succumb, but a proportion of seriously envenomed patients may exhibit clinical or laboratory evidence of myocardial insult. CASE DETAILS: An 88-year-old woman presented her dog to a veterinarian after it had sustained a bite by a witnessed snake, reportedly an eastern brown snake (Pseudonaja textilis, Elapidae). The woman became suddenly confused, and lost consciousness at the veterinary office. After transport to hospital, she denied any contact with the snake, but developed large haematomas at intravenous (i.v.) catheter insertion sites; blood tests revealed a severe defibrination coagulopathy, consistent with envenoming by a brown snake. An SVDK-tested urine sample was negative. A non-contrast CT of her head showed a minor subacute infarction of the left corona radiata. A twelve-lead ECG was normal, but her troponins were mildly elevated (39 ng/L). A diagnosis of brown snake envenoming was made and she received 2 vials of brown snake AV i.v., without adverse incident. Thirty min post AV her Glasgow Coma Score (GCS) had improved from 13 to 15 (normal). At 3.5 h post AV all bleeding from i.v. sites ceased, although her troponin T level peaked at 639 ng/L, supporting a diagnosis of non-ST elevated myocardial infarction (NSTEMI). DISCUSSION: Severe brown snake envenoming may occur in the absence of a perceived bite, and AV is temporally associated with improvement in clinical findings and coagulopathy. However, severe envenoming by this species can be complicated by cardiovascular events that in the circumstance of incomplete or absent history may confuse the primary diagnosis and affect patient outcome. PMID- 26153982 TI - MicroRNA-23b Inhibits the Proliferation and Migration of Heat-Denatured Fibroblasts by Targeting Smad3. AB - BACKGROUND: Skin grafting with the preservation of denatured dermis is a novel strategy for the treatment of burn-injured skin. Denatured dermis has the ability to restore to the morphology and function of normal skin, but the underlying molecular mechanism is elusive. MicroRNAs (miRNA) are small noncoding RNAs and regulate normal physiology as well as disease development. In this study, we assessed the potential role of miRNA-23b (miR-23b) in the regulation of cell proliferation and migration of heat-denatured fibroblasts and identified the underlying mechanism. METHODS: The expression of miR-23b in denatured dermis and heat-denatured fibroblasts was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and migration of heat-denatured fibroblasts were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated. RESULTS: miR-23b was downregulated in denatured dermis and heat-denatured fibroblasts. Downregulation of miR-23b dramatically promoted the proliferation and migration of heat-denatured fibroblasts. Subsequent analyses demonstrated that Smad3 was a direct and functional target of miR-23b in heat-denatured fibroblasts, which was validated by the dual luciferase reporter assay. Moreover, immunohistochemistry analysis showed that denatured dermis from rats displayed enhanced staining of Smad3. In addition, miR-23b modulated denatured dermis by activating the Notch1 and TGF beta signaling pathways. CONCLUSIONS: Our findings suggest that downregulation of miR-23b contributes to the recovery of denatured dermis, which may be valuable for treatment of skin burns. PMID- 26153984 TI - Diverse Early Life-History Strategies in Migratory Amazonian Catfish: Implications for Conservation and Management. AB - Animal migrations provide important ecological functions and can allow for increased biodiversity through habitat and niche diversification. However, aquatic migrations in general, and those of the world's largest fish in particular, are imperiled worldwide and are often poorly understood. Several species of large Amazonian catfish carry out some of the longest freshwater fish migrations in the world, travelling from the Amazon River estuary to the Andes foothills. These species are important apex predators in the main stem rivers of the Amazon Basin and make up the region's largest fishery. They are also the only species to utilize the entire Amazon Basin to complete their life cycle. Studies indicate both that the fisheries may be declining due to overfishing, and that the proposed and completed dams in their upstream range threaten spawning migrations. Despite this, surprisingly little is known about the details of these species' migrations, or their life history. Otolith microchemistry has been an effective method for quantifying and reconstructing fish migrations worldwide across multiple spatial scales and may provide a powerful tool to understand the movements of Amazonian migratory catfish. Our objective was to describe the migratory behaviors of the three most populous and commercially important migratory catfish species, Dourada (Brachyplatystoma rousseauxii), Piramutaba (Brachyplatystoma vaillantii), and Piraiba (Brachyplatystoma filamentosum). We collected fish from the mouth of the Amazon River and the Central Amazon and used strontium isotope signatures ((87)Sr/(86)Sr) recorded in their otoliths to determine the location of early rearing and subsequent. Fish location was determined through discriminant function classification, using water chemistry data from the literature as a training set. Where water chemistry data was unavailable, we successfully in predicted (87)Sr/(86)Sr isotope values using a regression-based approach that related the geology of the upstream watershed to the Sr isotope ratio. Our results provide the first reported otolith microchemical reconstruction of Brachyplatystoma migratory movements in the Amazon Basin. Our results indicate that juveniles exhibit diverse rearing strategies, rearing in both upstream and estuary environments. This contrasts with the prevailing understanding that juveniles rear in the estuary before migrating upstream; however, it is supported by some fisheries data that has indicated the presence of alternate spawning and rearing life-histories. The presence of alternate juvenile rearing strategies may have important implications for conservation and management of the fisheries in the region. PMID- 26153983 TI - Epstein-Barr Virus Proteins EBNA3A and EBNA3C Together Induce Expression of the Oncogenic MicroRNA Cluster miR-221/miR-222 and Ablate Expression of Its Target p57KIP2. AB - We show that two host-encoded primary RNAs (pri-miRs) and the corresponding microRNA (miR) clusters--widely reported to have cell transformation-associated activity--are regulated by EBNA3A and EBNA3C. Utilising a variety of EBV transformed lymphoblastoid cell lines (LCLs) carrying knockout-, revertant- or conditional-EBV recombinants, it was possible to demonstrate unambiguously that EBNA3A and EBNA3C are both required for transactivation of the oncogenic miR 221/miR-222 cluster that is expressed at high levels in multiple human tumours- including lymphoma/leukemia. ChIP, ChIP-seq, and chromosome conformation capture analyses indicate that this activation results from direct targeting of both EBV proteins to chromatin at the miR-221/miR-222 genomic locus and activation via a long-range interaction between enhancer elements and the transcription start site of a long non-coding pri-miR located 28 kb upstream of the miR sequences. Reduced levels of miR-221/miR-222 produced by inactivation or deletion of EBNA3A or EBNA3C resulted in increased expression of the cyclin-dependent kinase inhibitor p57KIP2, a well-established target of miR-221/miR-222. MiR blocking experiments confirmed that miR-221/miR-222 target p57KIP2 expression in LCLs. In contrast, EBNA3A and EBNA3C are necessary to silence the tumour suppressor cluster miR 143/miR-145, but here ChIP-seq suggests that repression is probably indirect. This miR cluster is frequently down-regulated or deleted in human cancer, however, the targets in B cells are unknown. Together these data indicate that EBNA3A and EBNA3C contribute to B cell transformation by inhibiting multiple tumour suppressor proteins, not only by direct repression of protein-encoding genes, but also by the manipulation of host long non-coding pri-miRs and miRs. PMID- 26153986 TI - Modeling credentials. PMID- 26153985 TI - BcMF26a and BcMF26b Are Duplicated Polygalacturonase Genes with Divergent Expression Patterns and Functions in Pollen Development and Pollen Tube Formation in Brassica campestris. AB - Polygalacturonase (PG) is one of the cell wall hydrolytic enzymes involving in pectin degradation. A comparison of two highly conserved duplicated PG genes, namely, Brassica campestris Male Fertility 26a (BcMF26a) and BcMF26b, revealed the different features of their expression patterns and functions. We found that these two genes were orthologous genes of At4g33440, and they originated from a chromosomal segmental duplication. Although structurally similar, their regulatory and intron sequences largely diverged. QRT-PCR analysis showed that the expression level of BcMF26b was higher than that of BcMF26a in almost all the tested organs and tissues in Brassica campestris. Promoter activity analysis showed that, at reproductive development stages, BcMF26b promoter was active in tapetum, pollen grains, and pistils, whereas BcMF26a promoter was only active in pistils. In the subcellular localization experiment, BcMF26a and BcMF26b proteins could be localized to the cell wall. When the two genes were co-inhibited, pollen intine was formed abnormally and pollen tubes could not grow or stretch. Moreover, the knockout mutants of At4g33440 delayed the growth of pollen tubes. Therefore, BcMF26a/b can participate in the construction of pollen wall by modulating intine information and BcMF26b may play a major role in co-inhibiting transformed plants. PMID- 26153987 TI - Immuno-oncology moves beyond PD-1. PMID- 26153991 TI - Migraine mAbs crowd into late-stage trials. PMID- 26153993 TI - Gene therapy 'cure' for blindness wanes. PMID- 26153994 TI - Alexion pays big for Synageva's rare disease drug candidate. PMID- 26153996 TI - Biotechs recoil at hedge fund manager's patent attacks. PMID- 26153997 TI - First stress-tolerant soybean gets go-ahead in Argentina. PMID- 26153999 TI - Saving rhinos with 3D printed horns. PMID- 26154000 TI - Research biotech patenting 2014. PMID- 26154001 TI - Will clinical trial data disclosure reduce incentives to develop new uses of drugs? PMID- 26154002 TI - Toward effective software solutions for big biology. PMID- 26154003 TI - The constrained prescription, interchangeability and substitution of biosimilars. PMID- 26154004 TI - Good laboratory practice for clinical next-generation sequencing informatics pipelines. PMID- 26154005 TI - Site-specific conjugation improves therapeutic index of antibody drug conjugates with high drug loading. PMID- 26154006 TI - A regulatory framework emerges for digital medicine. PMID- 26154007 TI - Public biotech in 2014--the numbers. PMID- 26154008 TI - Safe harbors in Europe: an update on the research and Bolar exemptions to patent infringement. PMID- 26154010 TI - Illuminating the dark matter of shotgun proteomics. PMID- 26154011 TI - Reigning in regulatory T-cell function. PMID- 26154012 TI - Molecular networks in context. PMID- 26154014 TI - Emerging network of resources for exploring paths beyond academia. PMID- 26154016 TI - Targeting CTCF to Control Virus Gene Expression: A Common Theme amongst Diverse DNA Viruses. AB - All viruses target host cell factors for successful life cycle completion. Transcriptional control of DNA viruses by host cell factors is important in the temporal and spatial regulation of virus gene expression. Many of these factors are recruited to enhance virus gene expression and thereby increase virus production, but host cell factors can also restrict virus gene expression and productivity of infection. CCCTC binding factor (CTCF) is a host cell DNA binding protein important for the regulation of genomic chromatin boundaries, transcriptional control and enhancer element usage. CTCF also functions in RNA polymerase II regulation and in doing so can influence co-transcriptional splicing events. Several DNA viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human papillomavirus (HPV) utilize CTCF to control virus gene expression and many studies have highlighted a role for CTCF in the persistence of these diverse oncogenic viruses. CTCF can both enhance and repress virus gene expression and in some cases CTCF increases the complexity of alternatively spliced transcripts. This review article will discuss the function of CTCF in the life cycle of DNA viruses in the context of known host cell CTCF functions. PMID- 26154018 TI - [The new editorship of HNO]. PMID- 26154017 TI - Genome Characterization, Prevalence and Distribution of a Macula-Like Virus from Apis mellifera and Varroa destructor. AB - Around 14 distinct virus species-complexes have been detected in honeybees, each with one or more strains or sub-species. Here we present the initial characterization of an entirely new virus species-complex discovered in honeybee (Apis mellifera L.) and varroa mite (Varroa destructor) samples from Europe and the USA. The virus has a naturally poly-adenylated RNA genome of about 6500 nucleotides with a genome organization and sequence similar to the Tymoviridae (Tymovirales; Tymoviridae), a predominantly plant-infecting virus family. Literature and laboratory analyses indicated that the virus had not previously been described. The virus is very common in French apiaries, mirroring the results from an extensive Belgian survey, but could not be detected in equally extensive Swedish and Norwegian bee disease surveys. The virus appears to be closely linked to varroa, with the highest prevalence found in varroa samples and a clear seasonal distribution peaking in autumn, coinciding with the natural varroa population development. Sub-genomic RNA analyses show that bees are definite hosts, while varroa is a possible host and likely vector. The tentative name of Bee Macula-like virus (BeeMLV) is therefore proposed. A second, distantly related Tymoviridae-like virus was also discovered in varroa transcriptomes, tentatively named Varroa Tymo-like virus (VTLV). PMID- 26154019 TI - How 'core' are motor timing difficulties in ADHD? A latent class comparison of pure and comorbid ADHD classes. AB - Children with attention-deficit/hyperactivity disorder (ADHD) have motor timing difficulties. This study examined whether affected motor timing accuracy and variability are specific for ADHD, or that comorbidity with autism spectrum disorders (ASD) contributes to these motor timing difficulties. An 80-trial motor timing task measuring accuracy (MU), variability (sigma) and infrequent long response times (tau) in estimating a 1-s interval was administered to 283 children and adolescents (8-17 years) from both a clinic and population based sample. They were divided into four latent classes based on the SCQ and CPRS-R: L data. These classes were: without behavioral problems 'Normal-class' (n = 154), with only ADHD symptoms 'ADHD-class' (n = 49), and two classes with both ASD and ADHD symptoms; ADHD(+ASD)-class (n = 39) and ASD(+ADHD)-class (n = 41). The pure ADHD-class did not deviate from the Normal class on any of the motor timing measures (mean RTs 916 and 925 ms, respectively). The comorbid ADHD(+ASD) and ASD(+ADHD) classes were significantly less accurate (more time underestimations) compared to the Normal class (mean RTs 847 and 870 ms, respectively). Variability in motor timing was reduced in the younger children in the ADHD(+ASD) class, which may reflect a tendency to rush the tedious task. Only patients with more severe behavioral symptoms show motor timing deficiencies. This cannot merely be explained by high ADHD severity with ASD playing no role, as ADHD symptom severity in the pure ADHD-class and the ASD(+ADHD) class was highly similar, with the former class showing no motor timing deficits. PMID- 26154021 TI - Riedel thyroiditis: Fine needle aspiration findings of a rare entity. AB - Riedel thyroiditis is a rare fibrosing disorder characterized by extension of the fibroinflammatory process beyond the thyroid capsule. Due to the nature of this lesion, fine-needle aspiration often yields scant material and may be interpreted as non-diagnostic. In this report, we describe cytologic features that allow the cytopathologist to favor a diagnosis of Riedel thyroiditis, thereby guiding appropriate further work-up and management. PMID- 26154023 TI - Low-level Mercury Exposure and Risk of Asthma in School-age Children. AB - BACKGROUND: Mercury (Hg) has been reported to have adverse effects on the immune system. However, the association between Hg exposure and asthma remains unclear. We hypothesized that blood Hg concentrations are associated with asthma and immune system blood profile changes in school-age children. METHODS: Between 2005 and 2010, we evaluated 4,350 Korean children at 7-8 years of age with no previous asthma diagnosis. Follow-up surveys were conducted twice, each 2 years apart, until 11-12 years of age. For every survey, we evaluated asthma through a questionnaire and blood profile. We analyzed the association of Hg concentration with asthma by logistic and Cox regression models and the association with blood profile by generalized additive and linear mixed models. RESULTS: Blood Hg concentrations at 7-8 years of age were associated with an increased risk of asthma (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0, 1.6) at ages up to 11-12 years (n = 191). Hg concentration was also associated with wheezing (OR = 1.2; 95% CI = 1.0, 1.3), asthma medication use (OR = 1.4; 95% CI = 0.97, 2.0), and airway hyperresponsiveness (OR = 1.2; 95% CI = 1.0, 1.3). Further adjustment for fish consumption did not change the results appreciably. CONCLUSIONS: Low-level Hg exposure was associated with asthma and blood profile changes in school-age children. PMID- 26154022 TI - The Web-Based Osteoarthritis Management Resource My Joint Pain Improves Quality of Care: A Quasi-Experimental Study. AB - BACKGROUND: Despite the availability of evidence-based guidelines for conservative treatment of osteoarthritis (OA), management is often confined to the use of analgesics and waiting for eventual total joint replacement. This suggests a gap in knowledge for persons with OA regarding the many different treatments available to them. OBJECTIVE: Our objective was to evaluate outcomes after usage of a Web-based resource called My Joint Pain that contains tailored, evidence-based information and tools aimed to improve self-management of OA on self-management and change in knowledge. METHODS: A quasi-experimental design was used to evaluate the My Joint Pain website intervention over a 12-month period. The intervention provided participants with general and user-specific information, monthly assessments with validated instruments, and progress tracking tools. A nationwide convenience sample of 195 participants with self assessed hip and/or knee OA completed both baseline and 12-month questionnaires (users: n=104; nonusers: n=91). The primary outcome measure was the Health Evaluation Impact Questionnaire (heiQ) to evaluate 8 different domains (health directed activity, positive and active engagement in life, emotional distress, self-monitoring and insight, constructive attitudes and approaches, skill and technique acquisition, social integration and support, health service navigation) and the secondary outcome measure was the 17-item Osteoarthritis Quality Indicator (OAQI) questionnaire to evaluate the change in appropriateness of care received by participants. Independent t tests were used to compare changes between groups for the heiQ and chi-square tests to identify changes within and between groups from baseline to 12 months for each OAQI item. RESULTS: Baseline demographics between groups were similar for gender (152/195, 77.9% female), age (mean 60, SD 9 years) and body mass index (mean 31.1, SD 6.8 kg/m(2)). With the exception of health service navigation, mean effect sizes from all other heiQ domains showed a positive trend for My Joint Pain users compared to the nonusers, although the differences between groups did not reach statistical significance. Within-group changes also showed improvements among the users of the My Joint Pain website for self-management (absolute change score=15%, P=.03), lifestyle (absolute change score=16%, P=.02), and physical activity (absolute change score=11%, P=.04), with no significant improvements for the nonusers. Following 12 months of exposure to the website, there were significant improvements for users compared to nonusers in self-management (absolute change score 15% vs 2%, P=.001) and weight reduction (absolute change scores 3% vs -6%, P=.03) measured on the OAQI. CONCLUSIONS: The My Joint Pain Web resource does not significantly improve overall heiQ, but does improve other important aspects of quality of care in people with hip and/or knee OA. Further work is required to improve engagement with the website and the quality of information delivered in order to provide a greater impact. PMID- 26154020 TI - A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia. AB - Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ~10( 7) and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis. PMID- 26154024 TI - Amarogentin regulates self renewal pathways to restrict liver carcinogenesis in experimental mouse model. AB - Amarogentin, a secoiridoid glycoside isolated from medicinal plant Swertia chirata, was found to restrict CCl4 /N-nitrosodiethyl amine (NDEA) induced mouse liver carcinogenesis by modulating G1/S cell cycle check point and inducing apoptosis. To understand its therapeutic efficacy on stem cell self renewal pathways, prevalence of CD44 positive cancer stem cell (CSC) population, expressions (mRNA/protein) of some key regulatory genes of self renewal Wnt and Hedgehog pathways along with expressions of E-cadherin and EGFR were analyzed during the liver carcinogenesis and in liver cancer cell line HepG2. It was observed that amarogentin could significantly reduce CD44 positive CSCs in both pre and post initiation stages of carcinogenesis than carcinogen control mice. In Wnt pathway, amarogentin could inhibit expressions of beta-catenin, phospho beta catenin (Y-654) and activate expressions of antagonists sFRP1/2 and APC in the liver lesions. In Hedgehog pathway, decreased expressions of Gli1, sonic hedgehog ligand, and SMO along with up-regulation of PTCH1 were seen in the liver lesions due to amarogentin treatment. Moreover, amarogentin could up-regulate E-cadherin expression and down-regulate expression of EGFR in the liver lesions. Similarly, amarogentin could inhibit HepG2 cell growth along with expression and prevalence of CD44 positive CSCs. Similar to in vivo analysis, amarogentin could modulate the expressions of the key regulatory genes of the Wnt and hedgehog pathways and EGFR in HepG2 cells. Thus, our data suggests that the restriction of liver carcinogenesis by amarogentin might be due to reduction of CD44 positive CSCs and modulation of the self renewal pathways. (c) 2015 Wiley Periodicals, Inc. PMID- 26154025 TI - Post-sinus surgery insertion of steroid-eluting bioabsorbable intranasal devices: A systematic review. AB - OBJECTIVES/HYPOTHESIS: Postendoscopic sinus surgery corticosteroid administration reduces polyp formation, inflammation, and adhesions. Steroid-eluting bioabsorbable intranasal devices (SEBID) are novel interventions thought to improve local drug delivery while minimizing systemic side effects. The primary aim of this systematic review is to evaluate the efficacy and safety of bioabsorbable SEBIDs. The secondary aim is to inform clinical recommendations and to introduce clinicians to this novel technology. STUDY DESIGN: MEDLINE, PubMed, Embase, and Cochrane Database were searched according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. METHODS: Original articles assessing the efficacy of SEBIDs inserted after endoscopic sinus surgery. For each study, we recorded the efficacy endpoints and safety outcomes. RESULTS: Seven studies met the inclusion criteria from 737 initial articles identified, including five prospective randomized controlled trials and two prospective single-cohort studies involving 394 sinuses within treatment arms. Patients were followed up for 2 to 6 months. Six studies demonstrated SEBID efficacy with statistical significance (P < 0.05). Steroid-eluting bioabsorbable intranasal devices were effective in reducing adhesion formation, polyp formation, inflammation, Lund-Kennedy scores, and perioperative sinus endoscopy scores. The devices improved patient-reported outcomes and olfaction while reducing postoperative interventions. They were not associated with adverse events and pose no ocular safety risk. Complications in three SEBID applications were reported. CONCLUSION: There is limited data available on SEBIDS; further studies are required to determine whether they are safe and effective adjuncts postendoscopic sinus surgery. Future studies are needed to optimize the dosing regimen, compare devices, and provide long-term outcomes. Steroid-eluting bioabsorbable intranasal devices may tentatively be incorporated into future evidence-based practice. PMID- 26154026 TI - Cytoskeletal and mitochondrial properties of bovine oocytes obtained by Ovum Pick Up: the effects of follicle stimulation and in vitro maturation. AB - Follicle stimulation by follicular stimulating hormone (FSH) is known to improve developmental competence of bovine oocytes obtained by Ovum Pick-Up (OPU); however, the exact factors in oocytes affected by this treatment have remained unclear. We compared in vitro matured (IVM) oocytes obtained at the immature stage from cows by OPU either without or with stimulation with FSH (non stimulated and stimulated OPU, respectively) to those obtained by superstimulation and in vivo maturation in terms of cytoskeleton morphology, mitochondrial distribution, intracellular adenosine triphosphate (ATP) content and H2 O2 levels at the metaphase-II stage and intracellular Ca(2+) levels after in vitro fertilization (IVF). Confocal microscopy after immunostaining revealed reduced size of the meiotic spindle, associated with increased tendencies of microfilament degradation and insufficient mitochondrial re-distribution in non stimulated OPU-derived IVM oocytes compared with those collected by stimulated OPU, which in turn resembled in vivo matured oocytes. However, there was no difference in mitochondrial functions between oocytes obtained by stimulated or non-stimulated OPU in terms of ATP content, cytoplasmic H2 O2 levels, base Ca(2+) levels and the frequencies and amplitudes of Ca(2+) oscillations after IVF. Larger size of metaphase spindles in oocytes obtained by stimulated OPU may reflect and potentially contribute to their high developmental competence. PMID- 26154027 TI - Safety challenges of medical equipment in nurse anaesthetist training in Haiti. AB - Safety challenges related to the use of medical equipment were investigated during the training of nurse anaesthetists in Haiti, using a systems approach to Human Factors and Ergonomics (HFE). The Observable Performance Obstacles tool, based on the Systems Engineering Initiative for Patient Safety (SEIPS) model, was used in combination with exploratory observations during 13 surgical procedures, to identify performance obstacles created by the systemic interrelationships of medical equipment. The identification of performance obstacles is an effective way to study the accumulation of latent factors and risk hazards, and understand its implications in practice and behaviour of healthcare practitioners. In total, 123 performance obstacles were identified, of which the majority was related to environmental and organizational aspects. These findings show how the performance of nurse anaesthetists and their relation to medical equipment is continuously affected by more than user-related aspects. The contribution of systemic performance obstacles and coping strategies to enrich system design interventions and improve healthcare system is highlighted. In addition, methodological challenges of HFE research in low-resource settings related to professional culture and habits, and the potential of community ergonomics as a problem managing approach are described. PMID- 26154028 TI - Crystal Structures of a Hyperthermophilic Archaeal Homoserine Dehydrogenase Suggest a Novel Cofactor Binding Mode for Oxidoreductases. AB - NAD(P)-dependent dehydrogenases differ according to their coenzyme preference: some prefer NAD, others NADP, and still others exhibit dual cofactor specificity. The structure of a newly identified archaeal homoserine dehydrogenase showed this enzyme to have a strong preference for NADP. However, NADP did not act as a cofactor with this enzyme, but as a strong inhibitor of NAD-dependent homoserine oxidation. Structural analysis and site-directed mutagenesis showed that the large number of interactions between the cofactor and the enzyme are responsible for the lack of reactivity of the enzyme towards NADP. This observation suggests this enzyme exhibits a new variation on cofactor binding to a dehydrogenase: very strong NADP binding that acts as an obstacle to NAD(P)-dependent dehydrogenase catalytic activity. PMID- 26154029 TI - Infants Fed a Lower Calorie Formula With 2'FL Show Growth and 2'FL Uptake Like Breast-Fed Infants. AB - OBJECTIVES: The aim of the present study was to examine the growth and tolerance of infants fed infant formulas with a caloric density closer to human milk (HM) supplemented with human milk oligosaccharides (HMOs) and to study uptake of the HMOs. METHODS: A prospective, randomized, controlled, growth and tolerance study was conducted in healthy, singleton infants (birth weight >=2490 g), who were enrolled by day of life (DOL) 5. Formula-fed infants were randomized to 1 of 3 formulas with a caloric density of 64.3 kcal/dL. Each formula contained galactooligosaccharides, and the 2 experimental formulas contained varying levels (0.2 and 1.0 g/L) of the HMO 2'-fucosyllactose (2'FL). The 3 formula groups were compared with an HM-fed reference group. Infants were exclusively fed either formula (n = 189) or HM (n = 65) from enrollment to 119 DOL. 2'FL was measured in the blood and urine collected from a subset of infants at DOL 42 and 119, and in HM collected from breast-feeding mothers at DOL 42. RESULTS: There were no significant differences among any groups for weight, length, or head circumference growth during the 4-month study period. All of the formulas were well tolerated and comparable for average stool consistency, number of stools per day, and percent of feedings associated with spitting up or vomit. 2'FL was present in the plasma and urine of infants fed 2'FL, and there were no significant differences in 2'FL uptake relative to the concentration fed. CONCLUSIONS: This is the first report of infants fed 2'FL-fortified formulas with a caloric density similar to HM. Growth and 2'FL uptake were similar to those of HM-fed infants. PMID- 26154030 TI - Adequacy of Infant Formula With Protein Content of 1.6 g/100 kcal for Infants Between 3 and 12 Months. AB - OBJECTIVES: Infant formulas provide more protein than breast milk. High protein intakes may place infants at risk of later obesity. The present study tested whether a formula with protein content below the regulatory level supports normal growth from age 3 months. METHODS: Randomized double-blind trial enrolled healthy infants less than age 3 months. At 3 months, formula-fed infants were assigned to experimental (EXPL, 1.61 g protein/100 kcal; modified bovine whey proteins with caseinoglycomacropeptide removed) or control (CTRL 2.15 g protein/100 kcal; unmodified bovine milk protein with a whey/casein ratio of 60/40) formula; breast fed (BF) infants were enrolled in a reference group. Complementary foods were allowed in small amounts from 4 to 6 months and unrestricted after 6 months. RESULTS: Weight gain (g/day) from 3 to 6 months was similar in the EXPL and CTRL groups (EXPL-CTRL -0.84 g/day; 95% confidence interval -2.25 to 0.57) and faster in the EXPL and CTRL groups than in the BF group. Weight analyzed longitudinally from 4 to 12 months was lower in the EXPL group than in the CTRL group (P = 0.031) but higher than in the BF group (P < 0.0001). Longitudinal analysis of odds ratios from 4 to 12 months indicated fewer infants with weight >85th percentile in the EXPL group than in the CTRL group (P = 0.015). Length z scores were lower than, and body mass index z scores were similar to, World Health Organization Standards in all of the groups. Serum biochemical parameters in the EXPL group reflected lower protein intake and were closer to parameters in the BF infants than in the CTRL group. CONCLUSIONS: A formula with 1.61 g of protein/100 kcal supports normal growth of infants after age 3 months. This protein content is adequate if provided from a high-quality source. PMID- 26154031 TI - Use of Biosimilars in Paediatric Inflammatory Bowel Disease: A Position Statement of the ESPGHAN Paediatric IBD Porto Group. AB - Because the patents for biopharmaceutical monoclonal antibodies have or soon will expire, biosimilars are coming to the market. This will most likely lead to decreased drug costs and so easier access to these expensive agents. Extrapolation, however, of the limited available clinical data from adults with rheumatologic diseases to children with inflammatory bowel disease (IBD) should be done with caution and needs some considerations.Postmarketing surveillance programs for efficacy, safety, and immunogenicity should become mandatory in children with IBD using biosimilars, as for all biological drugs. PMID- 26154032 TI - Caring for Women Who Have Experienced Female Genital Cutting. AB - Female genital cutting/mutilation (FGC/M) is a procedure that involves physically altering a woman's/girl's genitals for no health benefits. This is a practice that is deeply rooted in culture, religion, and social tradition primarily in some African and Middle East countries. It is performed by a midwife, barber, traditional healer with no surgical training, or a physician. The practice of FGC/M has been gaining increased attention as women from those countries have been migrating to the United States and Western Europe. The World Health Organization (WHO) has estimated that 125 million women worldwide have undergone FGC/M. The practice has serious short-term and long-term physical, obstetric, and psychological complications. It has been proposed by some healthcare professionals that physicians or other healthcare providers should perform the cutting because it would be done under more sanitary conditions that would reduce complications. However, the WHO and other organizations have condemned the practice by any medical professional. The FGC/M procedure is a human rights violation and has been banned by WHO and other organizations and governments. This article provides an overview of the current issues related to FGC/M and addresses important cultural considerations for nurses caring for women with FGC/M. Nurses are in a unique position to provide holistic, culturally competent care in a respectful, nonjudgmental atmosphere. Nurses have a role in educating women with FGC/M about the complications and care, as education is necessary in the challenge to eradicate the practice of FGC/M. PMID- 26154033 TI - A study on production of biodiesel using a novel solid oxide catalyst derived from waste. AB - The issues of energy security, dwindling supply and inflating price of fossil fuel have shifted the global focus towards fuel of renewable origin. Biodiesel, having renewable origin, has exhibited great potential as substitute for fossil fuels. The most common route of biodiesel production is through transesterification of vegetable oil in presence of homogeneous acid or base or solid oxide catalyst. But, the economics of biodiesel is not competitive with respect to fossil fuel due to high cost of production. The vegetable oil waste is a potential alternative for biodiesel production, particularly when disposal of used vegetable oil has been restricted in several countries. The present study evaluates the efficacy of a low-cost solid oxide catalyst derived from eggshell (a food waste) in transesterification of vegetable oil and simulated waste vegetable oil (SWVO). The impact of thermal treatment of vegetable oil (to simulate frying operation) on transesterification using eggshell-derived solid oxide catalyst (ESSO catalyst) was also evaluated along with the effect of varying reaction parameters. The study reported that around 90 % biodiesel yield was obtained with vegetable oil at methanol/oil molar ratio of 18:1 in 3 h reaction time using 10 % ESSO catalyst. The biodiesel produced with ESSO catalyst from SWVO, thermally treated at 150 degrees C for 24 h, was found to conform with the biodiesel standard, but the yield was 5 % lower compared to that of the untreated oil. The utilization of waste vegetable oil along with waste eggshell as catalyst is significant for improving the overall economics of the biodiesel in the current market. The utilization of waste for societal benefit with the essence of sustainable development is the novelty of this work. PMID- 26154034 TI - Impact of biologically synthesized silver nanoparticles on the growth and physiological responses in Brassica rapa ssp. pekinensis. AB - Silver nanoparticles (AgNPs) were extensively used in various fields, particularly in medicine as an antimicrobial agent. The unavoidable and extensive usage of AgNPs in turn accumulates in the environment. Plants are the essential base of ecosystem and are ready to disturb by environmental pollutants. Therefore, in the present study, we have planned to evaluate the impact of biologically synthesized AgNPs on the essential food crop Chinese cabbage (Brassica rapa ssp. pekinensis). The effects of AgNP-induced plant morphological and physiological changes were investigated in different concentrations (100, 250, and 500 mg/L). The results of morphological features showed that AgNPs at lower concentrations (100 mg/L) exhibit growth-stimulating activity, whereas at higher concentrations (250 and 500 mg/L), particularly, 500 mg/L exhibited growth suppressing activities which are in terms of reduced root, shoot growth, and fresh biomass. The increased reactive oxygen species (ROS) generation, malondialdehyde production, anthocyanin biosynthesis, and decreased chlorophyll content were also more obviously present at higher concentrations of AgNPs. The concentration-dependent DNA damage was observed in the AgNP-treated plants. The molecular responses of AgNPs indicate that most of the genes related to secondary metabolism (glucosinolates, anthocyanin) and antioxidant activities were induced at higher concentrations of AgNP treatment. The dose-dependent phytotoxicity effects of AgNPs were also observed. Taken together, the highest concentration of AgNPs (500 mg/L) could induce growth-suppressing activities via the induction of ROS generation and other molecular changes in B. rapa seedlings. PMID- 26154035 TI - Leaching behaviour and environmental risk assessment of heavy metals from electronic solder in acidified soil. AB - The leaching behaviour of Sn and Pb elements from eutectic SnPb solder of electronic waste in acidic soil was investigated through acidification with HCl H2SO4 solution and compared with saline solution. The amounts of Sn and Pb elements leached, when subjected to acidic soil, are higher than those with saline soil. Evidence for the significantly preferential release of Sn into the leachate is provided; the galvanic couple accelerated such preferential release. Surface product analysis reveals the slight damage of SnPb in saline soil. Serious dissolution due to electrochemical reaction and a thick, porous PbSO4 surface layer are observed in acidified soil, suggesting more severe toxicity potential of Pb in soil rather than in water. PMID- 26154036 TI - Evaluation of silver nanoparticles toxicity of Arachis hypogaea peel extracts and its larvicidal activity against malaria and dengue vectors. AB - Silver nanoparticles (AgNPs) were successfully synthesised from aqueous silver nitrate using the extracts of Arachis hypogaea peels. The synthesised SNPs were characterized by Fourier transform-infrared spectroscopy analysis, X-ray diffraction, transmission electron microscopy analysis and high-resonance scanning electron microscopy, and energy dispersive X-ray spectroscopy. AgNPs were well defined and measured 20 to 50 nm in size. The nanoparticles were crystallized with a face-centered cubic structure. Larvicidal activity of synthesised AgNPs from A. hypogaea peels was tested for their larvicidal activity against the fourth instar larvae of Aedes aegypti (Yellow fever), Anopheles stephensi (Human malaria). The results suggest that the synthesised AgNPs have the potential to be used as an ideal eco-friendly resource for the control of A. aegypti and A. stephensi. This study provides the first report on the mosquito larvicidal activity of synthesised AgNPs from A. hypogaea peels against vectors of malaria and dengue. PMID- 26154037 TI - Removal efficiencies for 136 tetra- through octa-chlorinated dibenzo-p-dioxins and dibenzofuran congeners with activated carbons. AB - In this study, the removal efficiency of 136 tetra- to octa-chlorinated dibenzo-p dioxin (CDD)/furan (F) congeners from a nitrogen + oxygen carrier gas was studied using a laboratory-scale, fixed bed adsorption system. Two kinds of activated carbon with dissimilar pore structures were used as adsorbents. The total concentration of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) in the source gas was 541 ng/Nm(3) and that of the 17 toxic 2,3,7,8-substituted PCDD/Fs 96.35 ng/Nm(3), accounting for 17.8% of the total original weight amount. Their toxic equivalent quantity (TEQ) was 8.31 ng I-TEQ/Nm(3). For both activated carbons, the removal efficiencies of the ten PCDD/F homologue groups rise with chlorine substitution number. The removal efficiencies vary approximately as a power function of vapor pressure (correlation coefficients r(2) = 0.93 and 0.81, respectively). Competitive adsorption and desorption occur as adsorption time went on, causing elution of the lower chlorinated homologues, i.e. tetra-CDD/F and Penta-CDD/F congeners. In addition, there are significantly different concentration distributions for isomers in the same homologue groups. However, their removal efficiencies have weak correlation with their initial concentrations. The correlation coefficients are from -0.47 to 0.32 and from 0.57 to 0.46 respectively for the two kinds of activated carbons. PMID- 26154038 TI - Characterization of the microbial community structure and the physicochemical properties of produced water and seawater from the Hibernia oil production platform. AB - Hibernia is Canada's largest offshore oil platform. Produced water is the major waste byproduct discharged into the ocean. In order to evaluate different potential disposal methods, a comprehensive study was performed to determine the impact from the discharge. Microorganisms are typically the first organisms to respond to changes in their environment. The objectives were to characterize the microbial communities and the chemical composition in the produced water and to characterize changes in the seawater bacterial community around the platform. The results from chemical, physicochemical, and microbial analyses revealed that the discharge did not have a detectable effect on the surrounding seawater. The seawater bacterial community was relatively stable, spatially. Unique microorganisms like Thermoanaerobacter were found in the produced water. Thermoanaerobacter-specific q-PCR and nested-PCR primers were designed, and both methods demonstrated that Thermoanaerobacter was present in seawater up to 1000 m from the platform. These methods could be used to track the dispersion of produced water into the surrounding ocean. PMID- 26154039 TI - On the role of hydrophobic Si-based protective coatings in limiting mortar deterioration. AB - In order to avoid both natural and artificial stone decay, mainly due to the interaction with atmospheric pollutants (both gases such as NOx and SO2 and particulate matter), polymeric materials have been widely studied as protective coatings enable to limit the penetration of fluids into the bulk material. In the current work, an air hardening calcic lime mortar (ALM) and a natural hydraulic lime mortar (HLM) were used as substrates, and commercially available Si-based resins (Alpha(r)SI30 and Silres(r)BS16) were adopted as protective agents to give hydrophobicity features to the artificial stones. Surface properties of coatings and their performance as hydrophobic agents were studied using different techniques such as contact angle measurements, capillary absorption test, mercury intrusion porosimetry, surface free energy, colorimetric measurements and water vapour permeability tests. Finally, some exposure tests to UV radiation and to real polluted atmospheric environments (a city centre and an urban background site) were carried out during a wintertime period (when the concentrations of the main atmospheric pollutants are higher) in order to study the durability of the coating systems applied. The effectiveness of the two commercial resins in reducing salt formation (sulphate and nitrate), induced by the interaction of the mortars with the atmospheric pollutants, was demonstrated in the case of the HLM mortar. Graphical Abstract ?. PMID- 26154040 TI - Response difference of transgenic and conventional rice (Oryza sativa) to nanoparticles (gammaFe2O3). AB - Nanoparticles (NPs) are an increasingly common contaminant in agro-environments, and their potential effect on genetically modified (GM) crops has been largely unexplored. GM crop exposure to NPs is likely to increase as both technologies develop. To better understand the implications of nanoparticles on GM plants in agriculture, we performed a glasshouse study to quantify the uptake of Fe2O3 NPs on transgenic and non-transgenic rice plants. We measured nutrient concentrations, biomass, enzyme activity, and the concentration of two phytohormones, abscisic acid (ABA) and indole-3-acetic acid (IAA), and malondialdehyde (MDA). Root phytohormone inhibition was positively correlated with Fe2O3 NP concentrations, indicating that Fe2O3 had a significant influence on the production of these hormones. The activities of antioxidant enzymes were significantly higher as a factor of low Fe2O3 NP treatment concentration and significantly lower at high NP concentrations, but only among transgenic plants. There was also a positive correlation between the treatment concentration of Fe2O3 and iron accumulation, and the magnitude of this effect was greatest among non-transgenic plants. The differences in root phytohormone production and antioxidant enzyme activity between transgenic and non-transgenic rice plants in vivo suggests that GM crops may react to NP exposure differently than conventional crops. It is the first study of NPs that may have an impact on GM crops, and a realistic significance for food security and food safety. PMID- 26154041 TI - Efficacy of silicon priming and fertigation to modulate seedling's vigor and ion homeostasis of wheat (Triticum aestivum L.) under saline environment. AB - Seed preconditioning, a short gun approach to modulate the effects of abiotic stresses on crop plants, has recently gained considerable attention of the researchers to induce salinity tolerance in agronomically important crops. The present study was conducted to explore the comparative efficacy of presowing seed priming with silicon (Si) and Si fertigation to modulate the wheat growth and ion dynamics. Seeds of wheat variety, PUNJAB-11, were sown in Petri plates having nutrient solutions with (120 mM) and without NaCl. Six levels of Si (0, 10, 20, 30, 40, or 50 mM), applied as sodium silicate (Na2SiO3), were tested either as a seed priming agent or as a supplement in the nutrient solution. Priming of seeds with Si mitigated the adverse effects of salinity stress on germination percentage, root as well as shoot length, dry and fresh weight. Application of Si either as preconditioning of seeds or addition in the growth medium resulted in reduced accumulation of sodium (Na(+)) in wheat seedlings under saline environment. Seedling's potassium (K(+)) contents either remained unaffected or decreased whereas calcium (Ca(2+)) contents decreased at all Si concentrations except at 30 mM when Si primed seeds were grown under salt stress. Addition of Si, under salt stress, in cultivation medium exerted a positive effect on seedling's K(+) and Ca(2+) contents. Silicon contribution to decontamination strategies was evaluated. PMID- 26154042 TI - Performance of three small-scale wastewater treatment plants. A challenge for possible re use. AB - The study focused on the assessment of the performance of three WWTPs in Greece by the estimation of the microbiological and chemical quality of influent and effluent sewage. Physicochemical parameters were recorded (temperature, pH, COD, BOD, suspended solids, conductivity), and meteorological data were collected (air temperature, rain). Microbiological parameters were analyzed (Escherichia coli, total coliforms, bacteriophages, Salmonella, human adenoviruses, Candida, Pseudallescheria boydii, helminths, parasites Cryptosporidium ssp., and Giardia spp.). Statistically significant correlations among the various aforementioned parameters were investigated, in an attempt to propose appropriate processing performance indicators. Furthermore, the study aimed to assess current joint ministerial decision (JMD) on wastewater reuse, for irrigation purposes; to evaluate its practicability and its potential for public health protection. In the vast majority, outlet samples from all three studied WWTPs were not appropriate for irrigation reuse purposes based on BOD50 and suspended solids limit values, set by the current JMD, for both limited and unrestricted irrigation applications. Reductions for E. coli, total coliforms, and bacteriophages were found to range between 2-3, 1.5-2.5, and 2-4 log10 values, respectively. Salmonella spp. was detected in outlet sewage samples from Patra (PAT), Arachova (ARH), and Livadeia (LEV), at 23% (3/13), 33% (4/12), and 38% (5/13), respectively. Molds were detected at 92.3% (12/13), 100% (13/13), and 91.6% (11/12), respectively, while Candida was found at 85% (11/13), 67% (8/12), and 46% (6/13). A high prevalence of Pseudallescheria boydii, in outlet samples from all studied WWTPs is an important public health issue, which underlines the need for further studies on this emerging fungal pathogen in wastewater reuse applications. Pseudallescheria boydii was found at 85% (11/13), 67% (8/12), and 46% (6/13), respectively. Helminths were found in both inlet and outlet samples, of all studied WWTPs, at 100%. Human adenoviruses, were detected at high percentages in outlet samples at 76.9% (10/13), 92.3% (12/13), 84.6% (11/13), respectively, while no influence of UV irradiation was recorded on the entry and exit loads of human adenoviruses. No influence of meteorological parameters was found on the microbiological and chemical parameters, with the exception of a weak positive correlation between environmental temperature and bacteriophages. A moderate positive correlation was found between BOD and suspended solids, bacteriophages, and total coliforms, bacteriophages and E. coli, and bacteriophages and adenoviruses. A significant positive correlation was found between total coliforms and E. coli, COD and BOD, and suspended solids and COD. No correlations were proved between human pathogens and bacterial indicator parameters. Collectively, our findings underlined the unsuitability of the current JMD on wastewater reuse in Greece, or public health protection. The study is expected to support the development of a public health risk assessment model based on quantitative risk assessment on the use of treated wastewater for irrigation purposes in Greece. PMID- 26154043 TI - Identification of Scirpus triqueter root exudates and the effects of organic acids on desorption and bioavailability of pyrene and lead in co-contaminated wetland soils. AB - Root exudates (REs) of Scirpus triqueter were extracted from the rhizosphere soil in this study. The components in the REs were identified by GC-MS. Many organic acids, such as hexadecanoic acid, pentadecanoic acid, vanillic acid, octadecanoic acid, citric acid, succinic acid, glutaric acid, and so on, were found. Batch simulated experiments were conducted to evaluate the impacts of different organic acids, such as citric acid, artificial root exudates (ARE), succinic acid, and glutaric acid in REs of S. triqueter on desorption of pyrene (PYR) and lead (Pb) in co-contaminated wetland soils. The desorption amount of PYR and Pb increased with the rise in concentrations of organic acids in the range of 0-50 g.L(-1), within shaking time of 2-24 h. The desorption effects of PYR and Pb in soils with various organic acids treatments decreased in the following order: citric acid > ARE > succinic acid > glutaric acid. The desorption rate of PYR and Pb was higher in co-contaminated soil than in single pollution soil. The impacts of organic acids in REs of S. triqueter on bioavailability of PYR and Pb suggested that organic acids enhanced the bioavailability of PYR and Pb in wetland soil, and the bioavailability effects of organic acids generally followed the same order as that of desorption effects. PMID- 26154044 TI - Oxygen, carbon, and nutrient exchanges at the sediment-water interface in the Mar Piccolo of Taranto (Ionian Sea, southern Italy). AB - In the shallow environment, the nutrient and carbon exchanges at the sediment water interface contribute significantly to determine the trophic status of the whole water column. The intensity of the allochthonous input in a coastal environment subjected to strong anthropogenic pressures determines an increase in the benthic oxygen demand leading to depressed oxygen levels in the bottom waters. Anoxic conditions resulting from organic enrichment can enhance the exchange of nutrients between sediments and the overlying water. In the present study, carbon and nutrient fluxes at the sediment-water interface were measured at two experimental sites, one highly and one moderately contaminated, as reference point. In situ benthic flux measurements of dissolved species (O2, DIC, DOC, N-NO3 (-), N-NO2 (-), N-NH4 (+), P-PO4 (3-), Si-Si(OH)4, H2S) were conducted using benthic chambers. Furthermore, undisturbed sediment cores were collected for analyses of total and organic C, total N, and biopolymeric carbon (carbohydrates, proteins, and lipids) as well as of dissolved species in porewaters and supernatant in order to calculate the diffusive fluxes. The sediments were characterized by suboxic to anoxic conditions with redox values more negative in the highly contaminated site, which was also characterized by higher biopolymeric carbon content (most of all lipids), lower C/N ratios and generally higher diffusive fluxes, which could result in a higher release of contaminants. A great difference was observed between diffusive and in situ benthic fluxes suggesting the enhancing of fluxes by bioturbation and the occurrence of biogeochemically important processes at the sediment-water interface. The multi-contamination of both inorganic and organic pollutants, in the sediments of the Mar Piccolo of Taranto (declared SIN in 1998), potentially transferable to the water column and to the aquatic trophic chain, is of serious concern for its ecological relevance, also considering the widespread fishing and mussel farming activities in the area. PMID- 26154045 TI - Synthesis of silver and gold nanoparticles using Jasminum nervosum leaf extract and its larvicidal activity against filarial and arboviral vector Culex quinquefasciatus Say (Diptera: Culicidae). AB - Silver and gold nanoparticles of Jasminum nervosum L. had unique optical properties such as broad absorbance band in the visible region of the electromagnetic spectrum. Characterization of the nanoparticles using UV spectrophotometer, Fourier transform infrared spectroscopy, X-ray diffraction, and transmission electron microscopy confirmed that the particles were silver (AgNPs) and gold (AuNPs) ranging between 4-22 and 2-20 nm with an average particles size of 9.4 and 10 nm, respectively. AgNPs and AuNPs of J. nervosum had high larvicidal activity on the filarial and arboviral vector, Culex quinquefasciatus, than the leaf aqueous extract. Observed lethal concentrations (LC50 and LC95) against the third instar larvae were 57.40 and 144.36 MUg/ml for AgNPs and 82.62 and 254.68 MUg/ml for AuNPs after 24 h treatment, respectively. The lethal time to kill 50% of C. quinquefasciatus larvae were 2.24 and 4.51 h at 150 MUg/ml of AgNPs and AuNPs, respectively, while in the case of aqueous leaf extract of J. nervosum it was 9.44 h at 500 MUg/ml (F 2,14 = 397.51, P < 0.0001). The principal component analysis plot presented differential clustering of the aqueous leaf extract, AgNP and AuNPs in relation to lethal dose and lethal time. It is concluded from the present findings that the biosynthesised AgNPs and AuNPs using leaf aqueous extract of J. nervosum could be an environmentally safer nanobiopesticide, and provided potential larvicidal effect on C. quinquefasciatus larvae which could be used for prevention of several dreadful diseases. PMID- 26154047 TI - A quantum chemical study of the omega-transaminase reaction mechanism. AB - omega-Transaminases are valuable tools in biocatalysis due to their stereospecificity and their broad substrate range. In the present study, the reaction mechanism of Chromobacterium violaceum omega-transaminase is investigated by means of density functional theory calculations. A large active site model is designed based on the recent X-ray crystal structure. The detailed energy profile for the half-transamination of (S)-1-phenylethylamine to acetophenone is calculated and the involved transition states and intermediates are characterized. The model suggests that the amino substrate forms an external aldimine with the coenzyme pyridoxal-5'-phosphate (PLP), through geminal diamine intermediates. The external aldimine is then deprotonated in the rate-determining step, forming a planar quinonoid intermediate. A ketimine is then formed, after which a hemiaminal is produced by the addition of water. Subsequently, the ketone product is obtained together with pyridoxamine-5'-phosphate (PMP). In the studied half-transamination reaction the ketone product is kinetically favored. The mechanism presented here will be valuable to enhance rational and semi-rational design of engineered enzyme variants in the development of omega-transaminase chemistry. PMID- 26154046 TI - Effects of bisphenol A on chlorophyll fluorescence in five plants. AB - The aim of this study was to evaluate the effects of bisphenol A (BPA) on plant photosynthesis and determine whether the photosynthetic response to BPA exposure varies in different plants. Chlorophyll fluorescence techniques were used to investigate the effects of BPA on chlorophyll fluorescence parameters in tomato (Lycopersicum esculentum), lettuce (Lactuca sativa), soybean (Glycine max), maize (Zea mays), and rice (Oryza sativa) seedlings. Low-dose (1.5 or 3.0 mg L(-1)) BPA exposure improved photosystem II efficiency, increased the absorption and conversion efficiency of primary light energy, and accelerated photosynthetic electron transport in each plant, all of which increased photosynthesis. These effects weakened or disappeared after the withdrawal of BPA. High-dose (10.0 mg L(-1)) BPA exposure damaged the photosystem II reaction center, inhibited the photochemical reaction, and caused excess energy to be released as heat. These effects were more evident after the highest BPA dose (17.2 mg L(-1)), but they weakened after the withdrawal of BPA. The magnitude of BPA exposure effects on the chlorophyll fluorescence parameters in the five plants followed the order: lettuce > tomato > soybean > maize > rice. The opposite order was observed following the removal of BPA. In conclusion, the chlorophyll fluorescence response in plants exposed to BPA depended on BPA dose and plant species. PMID- 26154048 TI - Exercise Metabolism. PMID- 26154049 TI - Cell Metabolism Clinical and Translational Reports. PMID- 26154050 TI - Exercise Metabolism: Historical Perspective. AB - The past 25 years have witnessed major advances in our knowledge of how exercise activates cellular, molecular, and biochemical pathways with regulatory roles in training response adaptation, and how muscle "cross-talk" with other organs is a mechanism by which physical activity exerts its beneficial effects on "whole body" health. However, during the late 19(th) and early 20(th) centuries, scientific debate in the field of exercise metabolism centered on questions related to the sources of energy for muscular activity, diet-exercise manipulations to alter patterns of fuel utilization, as well as the factors limiting physical work capacity. Posing novel scientific questions and utilizing cutting-edge techniques, the contributions made by the great pioneers of the 19(th) and early 20(th) centuries laid the foundation on which much of our present knowledge of exercise metabolism is based and paved the way for future discoveries in the field. PMID- 26154051 TI - Looking Ahead Perspective: Where Will the Future of Exercise Biology Take Us? AB - The health-promoting benefits of exercise have been recognized for centuries, yet the molecular and cellular mechanisms for the acute and chronic adaptive response to a variety of physical activities remain incompletely described. This Perspective will take a forward view to highlight emerging questions and frontiers in the ever-changing landscape of exercise biology. The biology of exercise is complex, highly variable, and involves a myriad of adaptive responses in multiple organ systems. Given the multitude of changes that occur in each organ during exercise, future researchers will need to integrate tissue-specific responses with large-scale omics to resolve the integrated biology of exercise. The ultimate goal will be to understand how these system-wide, tissue-specific exercise-induced changes lead to measurable physiological outcomes at the whole body level to improve health and well-being. PMID- 26154052 TI - Lymphatic Vessels at the Heart of the Matter. AB - Emergent research in the past decades has brought to light the importance of lymphatic vessels in tissue homeostasis, immunity, metabolism, and inflammation. In Nature, Klotz et al. (2015) demonstrate that cardiac lymphatics have a unique ontology compared to visceral lymphatics and that promoting their growth can improve cardiac function following injury. PMID- 26154053 TI - Breaking the Barrier--Chaperone-Mediated Autophagy of Perilipins Regulates the Lipolytic Degradation of Fat. AB - Triglyceride hydrolysis by cytosolic and lysosomal lipases mobilizes fatty acids from lipid droplet stores. Kaushik and Cuervo (2015) found that chaperone mediated autophagy removes the protective barrier from the lipid droplet surface, facilitating lipolysis by cytosolic lipases and assembly of autolipophagosomes for subsequent lysosomal lipid degradation. PMID- 26154054 TI - Motivation to Eat-AgRP Neurons and Homeostatic Need. AB - Activation of AgRP neurons potently induces feeding behaviors; however, whether this activity is involved in motivations of feeding behavior is unclear. A recent study in Nature (Betley et al., 2015) reports that AgRP neuron activity conditions learned behavior by transmitting a negative-valence signal: linking AgRP neurons to the preference of environmental cues associated with homeostatic need. PMID- 26154055 TI - Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise. AB - Acylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding acyl-CoA precursors via the action of carnitine acetyltransferase (CrAT), a bidirectional mitochondrial matrix enzyme. We show here that contractile activity reverses acetylcarnitine flux in muscle, from net production and efflux at rest to net uptake and consumption during exercise. Disruption of this switch in mice with muscle-specific CrAT deficiency resulted in acetyl-CoA deficit, perturbed energy charge, and diminished exercise tolerance, whereas acetylcarnitine supplementation produced opposite outcomes in a CrAT-dependent manner. Likewise, in exercise-trained compared to untrained humans, post-exercise phosphocreatine recovery rates were positively associated with CrAT activity and coincided with dramatic shifts in muscle acetylcarnitine dynamics. These findings show acetylcarnitine serves as a critical acetyl buffer for working muscles and provide insight into potential therapeutic strategies for combatting exercise intolerance. PMID- 26154058 TI - SnapShot: Immunometabolism. AB - Immunometabolism is a burgeoning field dissecting the contribution of key metabolic pathways to immune cell development, fate, and behavior. This SnapShot provides an overview of the metabolic requirements driving immune responses in lymphocytes, T and B cells, as well as macrophages. PMID- 26154056 TI - The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORgammat and Controls Metabolic Disease. AB - A high-fat diet (HFD) induces metabolic disease and low-grade metabolic inflammation in response to changes in the intestinal microbiota through as-yet unknown mechanisms. Here, we show that a HFD-derived ileum microbiota is responsible for a decrease in Th17 cells of the lamina propria in axenic colonized mice. The HFD also changed the expression profiles of intestinal antigen-presenting cells and their ability to generate Th17 cells in vitro. Consistent with these data, the metabolic phenotype was mimicked in RORgammat deficient mice, which lack IL17 and IL22 function, and in the adoptive transfer experiment of T cells from RORgammat-deficient mice into Rag1-deficient mice. We conclude that the microbiota of the ileum regulates Th17 cell homeostasis in the small intestine and determines the outcome of metabolic disease. PMID- 26154057 TI - The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity. AB - FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3 ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. PMID- 26154059 TI - Kinetics of lung tissue factor expression and procoagulant activity in bleomycin induced acute lung injury. AB - BACKGROUND: Activation of coagulation by expression of tissue factor (TF) in the airspace is a hallmark of acute lung injury (ALI) but the timing of TF activation in relationship to increases in lung permeability and inflammation are unknown. METHODS: To test the hypothesis that TF is upregulated early in the course of acute bleomycin lung injury and precedes increased permeability and inflammation we studied the early course of bleomycin-induced ALI in mice. Mice were treated with 0.04U intratracheal bleomycin or vehicle control and bronchoalveolar lavage (BAL) and lung tissue were collected daily for 7 days. Whole lung TF mRNA was determined by QT-PCR. TF protein was assessed by ELISA and immunostaining. BAL procoagulant activity was measured by BAL clot time and thrombin-antithrombin complexes. Inflammation was assessed by BAL cell count, differentials and CXCL1/KC concentration. Lung permeability was assessed by BAL protein and lung wet to dry weight ratio. RESULTS: Expression of CXCL1 occurred by day 1. BAL protein and lung wet-to-dry weight ratio increased significantly by day 3. TF mRNA and BAL procoagulant activity peaked on day 4 while whole lung TF protein peaked on day 6. Changes in permeability and procoagulant activity preceded inflammatory cell influx which was maximal at day 6 while whole lung TF protein peaked along with inflammation. CONCLUSION: These data demonstrate that cytokine upregulation is the earliest response to bleomycin administration, followed by increased lung permeability, upregulation of TF, and recruitment of inflammatory cells. PMID- 26154060 TI - Self Powered Highly Enhanced Dual Wavelength ZnO@CdS Core-Shell Nanorod Arrays Photodetector: An Intelligent Pair. AB - On the face of the impending energy crisis, developing low-energy or even zero energy photoelectronic devices is extremely important. A multispectral photosensitivity feature of a self-powered device provides an additional powerful tool. We have developed an unprecedented high performance dual wavelength self powered ZnO@CdS/PEDOT:PSS core-shell nanorods array photodetector through a simple aqueous chemical method wherein a suitable band alignment between an intelligent material pair, i.e. ZnO and CdS, has been utilized. Besides a noteworthy advantage of the devices being that they show a very sharp and prominent dual wavelength photosensitivity, both the ultraviolet and visible light sensitivity (ratio of current under illumination (Iphoto)/current under dark (Idark)) of the device are two orders of higher magnitude than those of pristine ZnO, attaining values of 2.8 * 10(3) and 1.07 * 10(3), respectively. At the same time, temporal responses faster than 20 ms could be achieved with these solution-processed photodetectors. The present study provides a very important direction to engineer core-shell nanostructured devices for dual wavelength high photosensitivity. PMID- 26154061 TI - The Ontogeny of Gap Crossing Behaviour in Bornean Orangutans (Pongo pygmaeus wurmbii). AB - For orangutans, the largest predominantly arboreal primates, discontinuous canopy presents a particular challenge. The shortest gaps between trees lie between thin peripheral branches, which offer the least stability to large animals. The affordances of the forest canopy experienced by orangutans of different ages however, must vary substantially as adult males are an order of magnitude larger in size than infants during the early stages of locomotor independence. Orangutans have developed a diverse range of locomotor behaviour to cross gaps between trees, which vary in their physical and cognitive demands. The aims of this study were to examine the ontogeny of orangutan gap crossing behaviours and to determine which factors influence the distance orangutans crossed. A non invasive photographic technique was used to quantify forearm length as a measure of body size. We also recorded locomotor behaviour, support use and the distance crossed between trees. Our results suggest that gap crossing varies with both physical and cognitive development. More complex locomotor behaviours, which utilized compliant trunks and lianas, were used to cross the largest gaps, but these peaked in frequency much earlier than expected, between the ages of 4 and 5 years old, which probably reflects play behaviour to perfect locomotor techniques. Smaller individuals also crossed disproportionately large gaps relative to their size, by using support deformation. Our results suggest that orangutans acquire the full repertoire of gap crossing techniques, including the more cognitively demanding ones, before weaning, but adjust the frequency of the use of these techniques to their increasing body size. PMID- 26154062 TI - Theoretical Investigations toward the Asymmetric Insertion Reaction of Diazoester with Aldehyde Catalyzed by N-Protonated Chiral Oxazaborolidine: Mechanisms and Stereoselectivity. AB - In recent years, the N-protonated chiral oxazaborolidine has been utilized as the Lewis acid catalyst for the asymmetric insertion reaction, which is one of the most challenging topics in current organic chemistry. Nevertheless, the reaction mechanism, stereoselectivity, and regioselectivity of this novel insertion reaction are still unsettled to date. In this present work, the density functional theory (DFT) investigation has been performed to interrogate the mechanisms and stereoselectivities of the formal C-C/H insertion reaction between benzaldehyde and methyl alpha-benzyl diazoester catalyzed by the N-protonated chiral oxazaborolidine. For the reaction channel to produce the R-configured C-C insertion product as the predominant isomer, the catalytic cycle can be characterized by four steps: (i) the complexation of the aldehyde with catalyst, (ii) addition of the other reactant methyl alpha-benzyl diazoester, (iii) the removal of nitrogen concerted with the migration of phenyl group or hydrogen, and (iv) the dissociation of catalyst from the products. Our computational results show that the carbon-carbon bond formation step is the stereoselectivity determining step, and the reaction pathways associated with [1, 2]-phenyl group migration occur preferentially to those pathways associated with [1, 2]-hydrogen migration. The pathway leading to the R-configured product is the most favorable pathway among the possible stereoselective pathways. All these calculated outcomes align well with the experimental observations. The novel mechanistic insights should be valuable for understanding this kind of reaction. PMID- 26154063 TI - Affinity-mediated capture and release of amphiphilic copolymers for controlling antimicrobial activity. AB - Capture and release of amphiphilic copolymers by a nano-sized polysaccharide gel (nanogel) was controlled by altering the hydrophobic binding affinity between the copolymer chains and nanogel. The antimicrobial activity of captured copolymer chains was suppressed, and regained upon release from the nanogel. PMID- 26154064 TI - Multilevel and Multicomponent Layer-by-Layer Assembly for the Fabrication of Nanofibrillar Films. AB - In this study, we demonstrate multilevel and multicomponent layer-by-layer (LbL) assembly as a convenient and generally applicable method for the fabrication of nanofibrillar films by exploiting the dynamic nature of polymeric complexes. The alternate deposition of poly(allylamine hydrochloride)-methyl red (PAH-MR) complexes with poly(acrylic acid) (PAA) produces nanofibrillar PAH-MR/PAA films, which involves the disassembly of PAH-MR complexes, the subsequent assembly of PAH with PAA, and the PAA-induced assembly of MR molecules into MR nanofibrils via a pi-pi stacking interaction. The aqueous solution of weak polyelectrolyte PAA with a low solution pH plays an important role in fabricating nanofibrillar PAH-MR/PAA films because proton transfer from acidic PAA to MR molecules induces the formation of MR nanofibrils. The generality of the multilevel and multicomponent LbL assembly is verified by alternate assembly of complexes of 1 pyrenylbutyric acid (PYA) and PAH with PAA to fabricate PAH-PYA/PAA films with organized nanofibrillar structures. Unlike the traditional static LbL assembly, the multilevel and multicomponent LbL assembly is dynamic and more flexible and powerful in controlling the interfacial assembly process and in fabricating composite films with sophisticated structures. These characteristics of multilevel and multicomponent LbL assembly will enrich the functionalities of the LbL-assembled films. PMID- 26154065 TI - Organotrifluoroborates as attractive self-assembling systems: the case of bifunctional dipotassium phenylene-1,4-bis(trifluoroborate). AB - The first structure of an aromatic bis(trifluoroborate) dipotassium salt, elucidated by the combination of crystallography, DFT calculations, topological and non-covalent interaction analysis, discloses a 3D network undergoing spontaneous self-assembly thanks to the massive participation of weak intra- and intermolecular interactions for which fluorine atoms proved to play a leading role. PMID- 26154066 TI - Half of 30-Day Hospital Readmissions Among HIV-Infected Patients Are Potentially Preventable. AB - Thirty-day readmission rates, a widely utilized quality metric, are high among HIV-infected individuals. However, it is unknown how many 30-day readmissions are preventable, especially in HIV patients, who have been excluded from prior potentially preventable readmission analyses. We used electronic medical records to identify all readmissions within 30 days of discharge among HIV patients hospitalized at a large urban safety net hospital in 2011. Two independent reviewers assessed whether readmissions were potentially preventable using both published criteria and detailed chart review, how readmissions might have been prevented, and the phase of care deemed suboptimal (inpatient care, discharge planning, post-discharge). Of 1137 index admissions, 213 (19%) resulted in 30-day readmissions. These admissions occurred among 930 unique HIV patients, with 130 individuals (14%) experiencing 30-day readmissions. Of these 130, about half were determined to be potentially preventable using published criteria (53%) or implicit chart review (48%). Not taking antiretroviral therapy (ART) greatly increased the odds of a preventable readmission (OR 5.9, CI:2.4-14.8). Most of the preventable causes of readmission were attributed to suboptimal care during the index hospitalization. Half of 30-day readmission in HIV patients are potentially preventable. Increased focus on early ART initiation, adherence counseling, management of chronic conditions, and appropriate timing of discharge may help reduce readmissions in this vulnerable population. PMID- 26154067 TI - Predictors of Adherence to Relaxation Guided Imagery During Pregnancy in Women with Preterm Labor. AB - OBJECTIVES: To examine adherence to relaxation guided imagery in women experiencing preterm labor as well as predictors influencing adherence. METHODS: This study used a longitudinal follow-up approach. Each of the 57 participating women received a mini-MP3 player containing a 13-minute relaxation guided imagery audio program that they were instructed to follow daily until giving birth. Follow-up interviews were conducted weekly. A generalized estimating equation was used to predict adherence. RESULTS: The total adherence rate was 58%. Higher adherence was predicted by the presence of at least a college degree (p=0.006), greater perceived stress (p=0.006), a higher risk of preterm delivery (p<0.001), and greater relaxation effects (p=0.028). Older maternal age was associated with lower adherence (p=0.001). In addition, adherence decreased significantly over time (p<0.001). Adherence was not related to marital status, employment, parity, the baseline level of anxiety, or hospitalization. CONCLUSIONS: Pregnant women with a high risk for preterm birth and greater perceived stress showed higher adherence to relaxation guided imagery. For women with a lower adherence to relaxation guided imagery, health care professionals may consider individual preferences regarding relaxation techniques. PMID- 26154068 TI - Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth. AB - Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration. PMID- 26154069 TI - CXCR4-Targeted Nanocarriers for Triple Negative Breast Cancers. AB - CXCR4 is a cell membrane receptor that is overexpressed in triple-negative breast cancers and implicated in growth and metastasis of this disease. Using electrohydrodynamic cojetting, we prepared multicompartmental drug delivery carriers for CXCR4 targeting. The particles are comprised of a novel poly(lactide co-glycolide) derivative that allows for straightforward immobilization of 1,1' [1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] (Plerixafor), a small molecule with affinity for CXCR4. Targeted nanocarriers are selectively taken up by CXCR4-expressing cells and effectively block CXCR4 signaling. This study suggests that CXCR4 may be an effective target for nanocarrier-based therapies. PMID- 26154072 TI - Role of imaging in evaluation of sudden cardiac death risk in hypertrophic cardiomyopathy. AB - PURPOSE OF REVIEW: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and is associated with sudden cardiac death (SCD) - an uncommon but devastating clinical outcome. This review is designed to assess the role of imaging in established risk factor assessment and its role in emerging SCD risk stratification. RECENT FINDINGS: Recent publications have highlighted the crucial role of imaging in HCM SCD risk stratification. Left ventricular hypertrophy assessment remains the key imaging determinant of risk. Data continue to emerge on the role of systolic dysfunction, apical aneurysms, left atrial enlargement and left ventricular outflow tract obstruction as markers of risk. Quantitative assessment of delayed myocardial enhancement and T1 mapping on cardiac MRI continue to evolve. SUMMARY: Recent multicenter trials have allowed multivariate SCD risk assessment in large HCM cohorts. Given aggregate risk with presence of multiple risk factors, a single parameter should not be used in isolation to determine implantable cardiac defibrillator candidacy. Use of all available imaging data, including cardiac magnetic resonance tissue characterization, allows a comprehensive approach to SCD stratification and implantable cardiac defibrillator decision-making. PMID- 26154071 TI - Structural and molecular basis for the novel catalytic mechanism and evolution of DddP, an abundant peptidase-like bacterial Dimethylsulfoniopropionate lyase: a new enzyme from an old fold. AB - The microbial cleavage of dimethylsulfoniopropionate (DMSP) generates volatile dimethyl sulfide (DMS) and is an important step in global sulfur and carbon cycles. DddP is a DMSP lyase in marine bacteria, and the deduced dddP gene product is abundant in marine metagenomic data sets. However, DddP belongs to the M24 peptidase family according to sequence alignment. Peptidases hydrolyze C-N bonds, but DddP is deduced to cleave C-S bonds. Mechanisms responsible for this striking functional shift are currently unknown. We determined the structures of DMSP lyase RlDddP (the DddP from Ruegeria lacuscaerulensis ITI_1157) bound to inhibitory 2-(N-morpholino) ethanesulfonic acid or PO4 (3-) and of two mutants of RlDddP bound to acrylate. Based on structural, mutational and biochemical analyses, we characterized a new ion-shift catalytic mechanism of RlDddP for DMSP cleavage. Furthermore, we suggested the structural mechanism leading to the loss of peptidase activity and the subsequent development of DMSP lyase activity in DddP. This study sheds light on the catalytic mechanism and the divergent evolution of DddP, leading to a better understanding of marine bacterial DMSP catabolism and global DMS production. PMID- 26154073 TI - Imaging cardiac morphology in hypertrophic cardiomyopathy: recent advances. AB - PURPOSE OF REVIEW: To describe new cardiac MRI (CMR) findings on cardiac structure and myocardial composition in hypertrophic cardiomyopathy (HCM). RECENT FINDINGS: Quantitative CMR assessment of replacement fibrosis and interstitial fibrosis can risk stratify HCM patients for adverse outcomes. Patients with global LVH (increased LV mass index) have more adverse outcomes. The HCM phenotype with a spiral distribution of hypertrophy entails a good prognosis. Myocardial noncompaction can be associated with HCM, as are papillary muscle and mitral apparatus abnormalities. Genotype positive, phenotype negative relatives of HCM probands may be detected by myocardial motion abnormalities. Emerging CMR methods for myocardial fiber disarray and altered myocardial stiffness may shed more light on cardiac structure, function and outcomes in HCM in coming years. SUMMARY: CMR structural features of HCM, including severity and distribution of hypertrophy and fibrosis, can augment clinical evaluation of HCM. New CMR phenotypes, associated papillary muscle, mitral leaflet and myocardial noncompaction abnormalities, role of left atrial enlargement, findings in genotype positive phenotype negative HCM, and emerging methods for the detection of myocardial fiber disarray and altered myocardial stiffness may shed light in coming years. PMID- 26154075 TI - Curvature capillary migration of microspheres. AB - We address the question: how does capillarity propel microspheres along curvature gradients? For a particle on a fluid interface, there are two conditions that can apply at the three phase contact line: either the contact line adopts an equilibrium contact angle, or it can be pinned by kinetic trapping, e.g. at chemical heterogeneities, asperities, or other pinning sites on the particle surface. We formulate the curvature capillary energy for both scenarios for particles smaller than the capillary length and far from any pinning boundaries. The scale and range of the distortion made by the particle are set by the particle radius; we use singular perturbation methods to find the distortions and to rigorously evaluate the associated capillary energies. For particles with equilibrium contact angles, contrary to the literature, we find that the capillary energy is negligible, with the first contribution bounded to fourth order in the product of the particle radius and the deviatoric curvature of the host interface. For pinned contact lines, we find curvature capillary energies that are finite, with a functional form investigated previously by us for disks and microcylinders on curved interfaces. In experiments, we show microspheres migrate along deterministic trajectories toward regions of maximum deviatoric curvature with curvature capillary energies ranging from 6 * 10(3)-5 * 10(4)kBT. These data agree with the curvature capillary energy for the case of pinned contact lines. The underlying physics of this migration is a coupling of the interface deviatoric curvature with the quadrupolar mode of nanometric disturbances in the interface owing to the particle's contact line undulations. This work is an example of the major implications of nanometric roughness and contact line pinning for colloidal dynamics. PMID- 26154074 TI - Preventing heart failure: the role of physical activity. AB - PURPOSE OF REVIEW: Heart failure prevention is an important public health goal. Increased physical activity and exercise may help to prevent heart failure, as they are associated with reduced heart failure incidence and potentially act through a variety of mechanisms to slow disease progression. RECENT FINDINGS: Increased physical activity, higher cardiorespiratory fitness, and lower sedentary time are associated with reduced heart failure incidence. These associations are consistent for occurrence of heart failure with both preserved and reduced ejection fraction, the common subphenotypes of the condition. Physiologic cardiac and vascular remodeling occurs across the normal range of physical activity in the community, and regular exercise (four to five sessions per week) is necessary to mitigate age-associated reductions in ventricular compliance and cardiac mass. SUMMARY: Greater physical activity, less sedentary time, and improved cardiorespiratory fitness are associated with reductions in heart failure risk. Various mechanisms may explain these findings, including: reducing the prevalence of standard and novel cardiovascular risk factors, inhibiting pathologic cardiovascular remodeling, promoting physiologic remodeling, and improving cardiac, neurohormonal, skeletal muscle, pulmonary, renal, and vascular performance. Future research is needed to elucidate the optimal timing, duration, and modality of physical activity and exercise training necessary to prevent the development of heart failure. PMID- 26154076 TI - Substituted 2-(Dimethylamino)biphenyl-2'-carboxaldehydes as Substrates for Studying n->pi* Interactions and as a Promising Framework for Tracing the Burgi Dunitz Trajectory. AB - The Burgi-Dunitz trajectory traces points along the pathway of bond formation between a nucleophile and electrophile. Previous X-ray crystallographic studies of some molecules containing a nucleophilic nitrogen atom and electrophilic carbonyl group provided some initial evidence for various degrees of bond formation via initial n->pi* interactions. Observation of a complete set of points along the trajectory, however, has not yet been attained. In this paper, we present a DFT computational study investigating substituted 2 (dimethylamino)biphenyl-2'-carboxaldehydes as substrates for further examination of n->pi* interactions and as a potential framework for more complete tracing of the Burgi-Dunitz trajectory. These compounds are particulary suitable for study because of the rotational freedom granted by the C-C bond connecting the two aromatic rings allowing the molecule to choose the degree of interaction between the two complementary groups. The extent of interaction is measured by interatomic distance, NBO second-order perturbative analysis energies, volume of transferred electron density as provided by ETS-NOCV analysis, and differences in energies between models that allow for n->pi* interactions and those that do not. A series of substituted biphenyls are ultimately identified as future synthetic targets that have maximum potential for providing improved tracing of the Burgi Dunitz trajectory. PMID- 26154077 TI - In This Issue: The Multiple Facets of IL-17. AB - This issue of International Reviews of Immunology hosts a recurring special topic focused on T17 cells. The authors discuss the biology of this cell subset, its regulation and plasticity, along with its pivotal role in the immune defense against fungi. In addition, they address the several ways T17 cells are involved with processes such as tissue remodeling, and disease conditions such as inflammation. PMID- 26154078 TI - The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans. AB - The discovery of interleukin (IL)-17-mediated immunity has provided a robust framework upon which our current understanding of the mechanism involved in host defense against mucocutaneous candidiasis (CMC) has been built. Studies have shed light on how pattern recognition receptors expressed by innate immune cells recognize various components of Candida cell wall. Inborn errors of immunity affecting IL-17+ T cell differentiation have recently been defined, such as deficiencies of signal transducer and activator of transcription (STAT)3, STAT1, IL-12Rbeta1 and IL-12p40, and caspase recruitment domain 9. Impaired receptor ligand coupling was identified in patients with IL-17F and IL-17 receptor A (IL17RA) deficiency and autoimmune polyendocrine syndrome (APS) type 1. Mutation in the nuclear factor kappa B activator (ACT) 1 was described as a cause of impaired IL-17R-mediated signaling. CMC may be part of a complex clinical phenotype like in patients with deficiencies of STAT3, IL-12Rbeta1/IL-12p40 and APS-1 or may be the only or dominant phenotypic manifestation of disease which is referred to as CMC disease. CMCD may result from deficiencies of STAT1, IL-17F, IL-17RA and ACT1. In this review we discuss how recent research on IL-17-mediated immunity shed light on host defense against mucocutaneous infection by Candida and how the discovery of various germ-line mutations and the characterization of associated clinical phenotypes have provided insights into the role of CD4+IL-17+ lymphocytes in the regulation of anticandidal defense of body surfaces. PMID- 26154079 TI - The choice and measurement of fluence in photodynamic therapy for superficial basal cell carcinoma: reply from the authors. PMID- 26154082 TI - Identification of the First Highly Subtype-Selective Inhibitor of Human GABA Transporter GAT3. AB - Screening a library of small-molecule compounds using a cell line expressing human GABA transporter 3 (hGAT3) in a [(3)H]GABA uptake assay identified isatin derivatives as a new class of hGAT3 inhibitors. A subsequent structure-activity relationship (SAR) study led to the identification of hGAT3-selective inhibitors (i.e., compounds 20 and 34) that were superior to the reference hGAT3 inhibitor, (S)-SNAP-5114, in terms of potency (low micromolar IC50 values) and selectivity (>30-fold selective for hGAT3 over hGAT1/hGAT2/hBGT1). Further pharmacological characterization of compound 20 (5-(thiophen-2-yl)indoline-2,3-dione) revealed a noncompetitive mode of inhibition at hGAT3. This suggests that this compound class, which has no structural resemblance to GABA, has a binding site different from the substrate, GABA. This was supported by a molecular modeling study that suggested a unique binding site that matched the observed selectivity, inhibition kinetics, and SAR of the compound series. These compounds are the most potent GAT3 inhibitors reported to date that provide selectivity for GAT3 over other GABA transporter subtypes. PMID- 26154084 TI - How challenging is to establish parameters good enough to assess the repercussions of trials to fight obesity. PMID- 26154083 TI - Impact of Noncommunicable Disease Multimorbidity on Healthcare Utilisation and Out-Of-Pocket Expenditures in Middle-Income Countries: Cross Sectional Analysis. AB - BACKGROUND: The burden of non-communicable disease (NCDs) has grown rapidly in low- and middle-income countries (LMICs), where populations are ageing, with rising prevalence of multimorbidity (more than two co-existing chronic conditions) that will significantly increase pressure on already stretched health systems. We assess the impact of NCD multimorbidity on healthcare utilisation and out-of-pocket expenditures in six middle-income countries: China, Ghana, India, Mexico, Russia and South Africa. METHODS: Secondary analyses of cross-sectional data from adult participants (>18 years) in the WHO Study on Global Ageing and Adult Health (SAGE) 2007-2010. We used multiple logistic regression to determine socio-demographic correlates of multimorbidity. Association between the number of NCDs and healthcare utilisation as well as out-of-pocket spending was assessed using logistic, negative binominal and log-linear models. RESULTS: The prevalence of multimorbidity in the adult population varied from 3.9% in Ghana to 33.6% in Russia. Number of visits to doctors in primary and secondary care rose substantially for persons with increasing numbers of co-existing NCDs. Multimorbidity was associated with more outpatient visits in China (coefficient for number of NCD = 0.56, 95% CI = 0.46, 0.66), a higher likelihood of being hospitalised in India (AOR = 1.59, 95% CI = 1.45, 1.75), higher out-of-pocket expenditures for outpatient visits in India and China, and higher expenditures for hospital visits in Russia. Medicines constituted the largest proportion of out-of-pocket expenditures in persons with multimorbidity (88.3% for outpatient, 55.9% for inpatient visit in China) in most countries. CONCLUSION: Multimorbidity is associated with higher levels of healthcare utilisation and greater financial burden for individuals in middle-income countries. Our study supports the WHO call for universal health insurance and health service coverage in LMICs, particularly for vulnerable groups such as the elderly with multimorbidity. PMID- 26154085 TI - Obesity and dyslipidemia - an urgent matter in youth from the general population and in type 1 diabetic patients. PMID- 26154086 TI - Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice. AB - OBJECTIVE: Acarbose and trans-chalcone are glucosidase inhibitors whose beneficial effects have been demonstrated in diabetes. The present study aimed at investigating their potential effects in obesity. MATERIALS AND METHODS: NMRI male mice (n = 48) were subjected to a high fat diet for four weeks, which induced an initial state of obesity. One control group was given normal rodent diet. Obese animals were then switched to normal rodent diet, and divided to four groups (n = 12 in each): untreated, sham (receiving grape seed oil), and experimental groups receiving acarbose and trans-chalcone (12 mg/kg) during eight weeks. Body weight, blood glucose and other biochemical parameters including triglycerides (TG), cholesterol, HDL, AST, and ALT were measured, as well as leptin, adiponectin, TNF-alpha, and total antioxidant capacity (TAC). Histological studies were performed on adipose cells and liver tissue samples. RESULTS: All factors were affected in a positive manner by acarbose, save for body weight, blood sugar and leptin levels, on which acarbose effects, although observable, were not statistically significant. Grape seed oil, used as a solvent for trans-chalcone was found to possess significant effect on TG and TAC, and had beneficial effects on other factors including liver enzymes and cholesterol. Trans-chalcone effects were significant on HDL, leptin and ALT. All compounds seemed to be able to affect fat deposition in liver tissue, and decrease the size of adipose tissue cells to some extent. CONCLUSION: In conclusion, the tested compounds were able to affect lipid accumulation in tissues and influence adipokines, which may result in an enhanced state with regard to inflammation and oxidative stress. PMID- 26154087 TI - Swim training and the genetic expression of adipokines in monosodium glutamate treated obese rats. AB - OBJECTIVE: The aim of this study was to evaluate the genetic expression of adipokines in the adipocytes of monosodium glutamate (MSG)-treated obese rats submitted to physical activity. MATERIALS AND METHODS: Obesity was induced by neonatal MSG administration. Exercised rats (MSG and control) were subjected to swim training for 30 min for 10 weeks, whereas their respective controls remained sedentary. Total RNA was obtained from sections of the mesenteric adipose tissue of the rats. mRNA levels of adiponectin (Adipoq), tumor necrosis factor alpha (Tnf), peroxisome proliferator-activated receptor alpha (Ppara), and peroxisome proliferator-activated receptor gamma (Pparg) adipokines were quantified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS: In the exercise-trained control group, the expression of Adipoq increased compared to the sedentary control, which was not observed in the MSG-obese rats. Increased levels of Tnf in MSG-obese rats were not reversed by the swim training. The expression of Ppara was higher in sedentary MSG-obese rats compared to the sedentary control. Swimming increased this adipokine expression in the exercise trained control rats compared to the sedentary ones. mRNA levels of Pparg were higher in the sedentary MSG-rats compared to the sedentary control; however, the exercise did not influenced its expression in the groups analyzed. CONCLUSIONS: In conclusion, regular physical activity was not capable to correct the expression of proinflammatory adipokines in MSG-obese rat adipocytes. PMID- 26154088 TI - Dyslipidemia in young patients with type 1 diabetes mellitus. AB - OBJECTIVE: The association between type 1 diabetes mellitus (T1D) and dyslipidemia (DLP) increases the risk of cardiovascular disease (CVD). The aim of this study was to evaluate the presence of dyslipidemia in young T1D patients. MATERIALS AND METHODS: The study design was cross-sectional and descriptive. We reviewed medical records of T1D patients followed at an endocrinology service, from 1998-2012. DATA COLLECTED: gender, actual age and age at diagnosis, duration of T1D since diagnosis, body mass index (BMI), pubertal stage, glycemic control (GC) determined by glycated hemoglobin (HbA1c), total cholesterol (TC), HDL, LDL, triglycerides (TG). To analyze lipid profile and metabolic control, we used the Brazilian Society of Diabetes Guidelines. RESULTS: Were included 239 T1D patients, 136 (56.9%) females; mean +/- SD: actual age 15.7 +/- 5.0 years and at T1D diagnosis 7.3 +/- 3.9; T1D duration 10.6 +/- 6.4 years, 86.6% puberty, 15.1% overweight. The prevalence of DLP was 72.5%, 63.3% females, 86.6% puberty, mean +/- SD: actual age 15.4 +/- 4.8 years and at T1D diagnosis 7.2 +/- 4.1 years, duration of T1D 10.7 +/- 6.1 years. We found high-CT in 56.7%, low-HDL = 21.7%, high LDL = 44.0%, high-TG = 11.8%. Between females with DLP, 83.5% was in puberty. We find correlation between the presence of DLP, a poor GC and BMC. CONCLUSION: We found a high prevalence of DLP in young patients with T1D, particularly in puberty females. Programs targeting the prevention of dyslipidemia should be adopted, especially for this group, in order to prevent/delay chronic complications and cardiovascular disease. PMID- 26154089 TI - 2000 CDC or 2007 WHO - what is the most sensitive anthropometric reference for determination of overweight and cardio-metabolic risk in children aged 6-10 years? AB - OBJECTIVE: To compare the two anthropometric standards for screening of overweight and cardio-metabolic risk in 6-10-year-old children. SUBJECTS AND METHODS: This cross-sectional study included 175 subjects attending the Referral Center for the Treatment of Children and Adolescents in Campos, Rio de Janeiro. They were classified according to CDC and WHO BMI z scores as normal-weight (z score > -1 and < 1), overweight (z-score >= 1 and < 2) or obese (z-score >= 2). Sensitivities and specificities in predicting systolic (SBP), diastolic (DBP) blood pressure and homeostatic model assessment insulin resistance index (HOMA IR) alterations were calculated. RESULTS: There was a major difference in 11 children who rated overweight by the CDC but were reclassified as obese by the WHO. Their mean z-scores for SBP (1.71 +/- 1.54), DBP (2.64 +/- 1.83) and HOMA-IR (1.84 +/- 0.98) were higher than those classified as overweight by both references (SBP = 0.49 +/- 1.34, p < 0.023, DBP = 1.45 +/- 0.97, p < 0.04 and HOMA = 1.24 +/- 0.67, p < 0.04), but were similar to those classified as obese by both criteria (SBP = 1.25 +/- 2.04, p = 0.60, DBP = 1.94 +/- 1.19, p = 0.50 and HOMA = 2.09 +/- 1.12, p = 0.76). CONCLUSION: The 2007 WHO reference was the most sensitive in screening for overweight and alterations in blood pressure and HOMA IR in 6-10-year-old children. PMID- 26154090 TI - Risk factors for Charcot foot. AB - OBJECTIVE: Diabetes mellitus is the main cause of Charcot neuroarthropathy and is clinically classified as follows: Charcot foot, acute Charcot foot (ACF) when there is inflammation, and inactive Charcot foot when inflammatory signs are absent. The aim of this study was to identify the risk factors for ACF in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: A matched case control study was conducted to assess the factors associated with acute Charcot foot from February 2000 until September 2012. Four controls for each case were selected 47 cases of ACF and 188 controls without ACF were included. Cases and controls were matched by year of initialization of treatment. Conditional logistic regression was used to estimate matched odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: In multivariate analysis, patients having less than 55 years of age (adjusted OR = 4.10, 95% CI = 1.69 - 9.94), literate education age (adjusted OR = 3.73, 95% CI = 1.40 - 9.92), living alone (adjusted OR = 5.84, 95% CI = 1.49 - 22.86), previous ulceration (adjusted OR = 4.84, 95% CI = 1.62 - 14.51) were at increased risk of ACF. However, peripheral arterial disease (adjusted OR = 0.16, 95% CI = 0.05 - 0.52) of 6.25 (1.92 - 20.0) was a protective factor. DISCUSSION: The results suggest that PCA in type 2 diabetes primarily affects patients under 55 who live alone, are literate, and have a prior history of ulcers, and that peripheral arterial disease is a protective factor. PMID- 26154091 TI - Seasonal variation of haemoglobin A1c in a Portuguese adult population. AB - OBJECTIVE: Haemoglobin A1c (Hb A1c) is routinely used for monitoring glycemic control in patients with diabetes. Hb A1c seasonal fluctuations can be directly related to different biological, geographical and cultural influences. Our purpose was to evaluate seasonal variation of Hb A1c in a hospital-based adult population over a period of 5 years. MATERIALS AND METHODS: We analyzed retrospectively monthly Hb A1c mean values (DCCT, %) based on all the assays performed to adult patients at a tertiary care university Portuguese hospital between 2008-2012. RESULTS: We obtained 62,384 Hb A1c valid measurements, with a peak level found in January-February (7.1%), a trough in August-October (6.8%) and an average peak-to-trough amplitude value of 0.3%. This trend was observed in both genders and age subgroups evaluated. CONCLUSIONS: There is a Hb A1c circannual seasonal pattern with peak levels occurring in winter months in this Portuguese population. This finding should be recognized in daily clinical practice to warrant better clinical and epidemiological interpretation of Hb A1c values. PMID- 26154092 TI - Thyroid function, autoimmunity and nodules in hematological malignancies. AB - OBJECTIVE: Hematological malignancies encompass a large spectrum of disease entities whose treatment by chemo/radiotherapy could lead to thyroid complications. To the best of our knowledge, no study has simultaneously addressed thyroid function, autoimmunity and nodularity. Therefore, we decided to conduct one. MATERIALS AND METHODS: We evaluated 82 Caucasian patients (36 women and 46 men), who were treated at our Oncology division for hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphatic leukemia, non-Hodgkin lymphoma and polycythemia vera) and compared them with a control group of 104 patients. Patients who had received or were receiving external head/neck radiotherapy were excluded. All oncological patients and control individuals underwent thyroid ultrasonography and thyroid function and autoimmunity tests. RESULTS: A lower prevalence of enlarged thyroid and nodules were found in patients with respect to controls. The rate of thyroid nodules was the highest in multiple myeloma and polycythemia vera, and the lowest in chronic lymphatic leukemia. Non-Hodgkin lymphoma patients had the smallest thyroid nodules while men with multiple myeloma the biggest ones. No patient had hypothyroidism, while 5.6% of patients had subclinical hyperthyroidism. In contrast, within the control group the rates of hypothyroidism and hyperthyroidism, overt and subclinical, were 3.8%, 20.2%, 0% and 0% respectively. Moreover, the overall rate of thyroid autoantibody positiveness in patients was significantly lower than controls. CONCLUSION: In our experience, we found a significantly lower prevalence of thyroid abnormalities in hematologic patients who underwent chemotherapy, but not radiotherapy, with respect to controls. PMID- 26154093 TI - Effect of glycemic index on obesity control. AB - OBJECTIVE: Evaluate the effect of glycemic index (GI) on biochemical parameters, food intake, energy metabolism, anthropometric measures and body composition in overweight subjects. MATERIALS AND METHODS: Simple blind study, in which nineteen subjects were randomly assigned to consume in the laboratory two daily low GI (n = 10) or high GI (n = 9) meals, for forty-five consecutive days. Habitual food intake was assessed at baseline. Food intake, anthropometric measures and body composition were assessed at each 15 days. Energy metabolism and biochemical parameters were evaluated at baseline and the end of the study. RESULTS: Low GI meals increased fat oxidation, and reduced waist circumference and HOMA-IR, while high GI meals increased daily dietary fiber and energy intake compared to baseline. There was a higher reduction on waist circumference and body fat, and a higher increase on postprandial fat oxidation in response to the LGI meals than after high GI meals. High GI meals increased fasting respiratory coefficient compared to baseline and low GI meals. CONCLUSION: The results of the present study showed that the consumption of two daily low GI meals for forty-five consecutive days has a positive effect on obesity control, whereas, the consumption of high GI meals result has the opposite effect. PMID- 26154094 TI - Bone mineral density in short bowel syndrome: correlation with BMI and serum vitamins C, E and K. AB - OBJECTIVE: Bone loss has been established as a major extra-intestinal complication of short bowel syndrome (SBS). The purpose of this study was to correlate bone mineral density (BMD) with body mass index (BMI), serum vitamin and mineral levels in patients with SBS. MATERIAL AND METHODS: The study was conducted on 13 patients (8 male and 5 female, 54.7 +/- 11.4 years) with SBS (residual small bowel length of 10 to 100 cm). We determined the food ingestion, anthropometry, serum levels of vitamins C, A, D, E and K, as well as serum and urinary levels of phosphorus and calcium. BMD was measured by dual-energy x-ray absorptiometry (DXA). RESULTS: Osteopenia and osteoporosis was diagnosed in all but one SBS patient. Serum levels of vitamin D were low in all volunteers. Sixty one percent of patients had vitamin E deficiency; hypovitaminosis A and C occurred in one subject. BMI and C, E and K vitamin serum levels correlated with T-score of BMD. CONCLUSIONS: Osteopenia and osteoporosis were common in SBS patients. There was a correlation between BMD and the serum levels of vitamins C, E and K, an indicative that such vitamins may influence bone health. PMID- 26154095 TI - Pituitary apoplexy: pathophysiology, diagnosis and management. AB - Pituitary apoplexy is characterized by sudden increase in pituitary gland volume secondary to ischemia and/or necrosis, usually in a pituitary adenoma. Most cases occur during the 5th decade of life, predominantly in males and in previously unknown clinically non-functioning pituitary adenomas. There are some predisposing factors as arterial hypertension, anticoagulant therapy and major surgery. Clinical picture comprises headache, visual impairment, cranial nerve palsies and hypopituitarism. Most cases improve with both surgical and expectant management and the best approach in the acute phase is still controversial. Surgery, usually by transsphenoidal route, is indicated if consciousness and/or vision are impaired, despite glucocorticoid replacement and electrolyte support. Pituitary function is impaired in most patients before apoplexy and ACTH deficiency is common, which makes glucocorticoid replacement needed in most cases. Pituitary deficiencies, once established, usually do not recover, regardless the treatment. Sellar imaging and endocrinological function must be periodic reevaluated. PMID- 26154096 TI - The key role of 99mTc-MIBI SPECT/CT in the diagnosis of parathyroid adenoma: a case report. AB - The concomitant occurrence of primary hyperparathyroidism (PHPT) due to parathyroid adenoma and papillary thyroid carcinoma (PTC) is not common. The co occurrence of parathyroid tumors and thyroid diseases can lead to misdiagnosis owing to mutual interference of imaging in the early period of disease. The most commonly used imaging techniques for the preoperative localization of parathyroid and thyroid adenomas are technetium-99m sestamibi (99mTc-MIBI) scintigraphy and ultrasonography of the neck. Recently, 99mTc-MIBI single-photon emission computed tomography associated with computed tomography scintigraphy (SPECT/CT) has been used to detect PHPT, and its diagnostic value is being evaluated. Herein, we report a patient with an unusual co-occurrence of parathyroid adenoma and multiple thyroid diseases, including papillary thyroid carcinoma, thyroid adenoma and lymphocytic thyroiditis, which were localized with 99mTc-MIBI SPECT/CT and confirmed surgically. We suggest that 99mTc-MIBI SPECT/CT can play an important role in the diagnosis of parathyroid and thyroid lesions. PMID- 26154097 TI - Transformation of nonfunctioning pancreatic tumor into malignant insulinoma after 3 years: an uncommon clinical course of insulinoma. AB - A 62-year-old man admitted to our outpatient clinic with two months of recurrent life threatening hypoglycemia episodes. He was diagnosed as malignant insulinoma with multiple metastases of liver and peripancreatic lymph nodes. Liver biopsy specimen was demonstrated grade 2 neuroendocrine tumor compatible with clinical and radiological results. He was followed under the treatment of continuous intravenous glucose infusion during the diagnostic procedures. He had a pancreatic lesion history measured 20 x 12 mm in diameter via the abdominal tomography examination approximately two years before the diagnosis. Unusual course of this case suggests the transformation of nonfunctioning pancreatic neuroendocrine tumor into functional insulin secreting tumor with metastases. The patient was found inoperable and started on chemotherapy. PMID- 26154098 TI - Gene expression of estrogen receptor-alpha in orbital fibroblasts in Graves' ophthalmopathy. AB - Graves' ophthalmopathy (GO) is one of the most severe clinical manifestations of Graves' disease (GD), and its treatment might involve high-dose glucocorticoid therapy. The higher incidence of GO among females, and the reported association between polymorphisms of estrogen receptor (ER) and GD susceptibility have led us to question the role of estrogen and its receptor in GO pathogenesis. We, thus, assessed estrogen receptor-alpha (ERA) gene expression in cultures of orbital fibroblasts from a patient with GO before (controls) and after treatment with 10 nM and 100 nM dexamethasone (DEX). Orbital fibroblasts showed ERA gene expression. In the cells treated with 10 nM and 100 nM DEX, ERA gene expression was, respectively, 85% higher and 74% lower, than in the control group. We concluded that ERA gene expression is found in the orbital fibroblasts of patient with GO, which may be affected by glucocorticoids in a dose-related manner. Arch Endocrinol Metab. 2015;59(3):273-6. PMID- 26154099 TI - An unexpected cause of severe and refractory PTH-independent hypercalcemia: case report and literature review. AB - Hypercalcemia is a common condition in the internal medicine practice. Sometimes its cause is not readily apparent, so extensive investigation is appropriate. Here we report an unexpected cause for hypercalcemia in an elderly woman. The case of an 82-years old woman with PTH-independent hypercalcemia, lymphocytosis, normal serum 1,25 (OH)vitamin D levels, and low serum PTHrp levels, is described. Medical history and complementary investigation were unremarkable, except for increased metabolic activity in the glutei regions, as measured by whole body 18F FDG PET-CT. Reviewing her medical history, her sister recalled that she had been submitted to intramuscular methylmethacrylate injections, for cosmetic purposes, five years before presentation, which was confirmed by muscle biopsy. Low calcium intake, parenteral bisphosphonates, calcitonin, and glucocorticoids were used to control serum calcium levels. Methylmethacrylate injections, used cosmetically, are a new cause for hypercalcemia, even after many years. Hypercalcemia was probably due to calcitriol overproduction in foreign body granulomas. Persistent reactive lymphocytosis could be a clue for this inflammatory cause of hypercalcemia. PMID- 26154100 TI - Correction: sleep and glycemic control in type 1 diabetes. PMID- 26154101 TI - An improved cell membrane chromatography method for the simultaneous screening of two epidermal growth factor receptor antagonists from radix scutellariae. AB - A high-expression epidermal growth factor receptor cell membrane chromatography using the silica gel with the average particle size of 3 MUm as the stationary phase carrier coupled with high-performance liquid chromatography and mass spectrometry was established for the online screening of epidermal growth factor receptor antagonists from Radix Scutellariae (Huang Qin in Chinese), a traditional Chinese medicine. In this study, the growth factor receptor cell membrane chromatography model using the smaller particle size carrier showed a higher efficiency for simultaneous screening baicalein, another one of the potential epidermal growth factor receptor antagonists from Radix Scutellariae extract besides wogonin, which was found in our previous work. The molecular docking result showed the occupancy site and binding mode of baicalein and wogonin with epidermal growth factor receptor tyrosine kinase were similar to gefitinib. The result of the assay for the in vitro inhibitory activity showed that baicalein and wogonin inhibited the growth of the high-expression epidermal growth factor receptor cell in a dose-dependent manner and even achieved a better inhibition effect than gifitinib in the low-dosage range. PMID- 26154102 TI - Cationic Mucic Acid Polymer-Based siRNA Delivery Systems. AB - Nanoparticle (NP) delivery systems for small interfering RNA (siRNA) that have good systemic circulation and high nucleic acid content are highly desired for translation into clinical use. Here, a family of cationic mucic acid-containing polymers is synthesized and shown to assemble with siRNA to form NPs. A cationic mucic acid polymer (cMAP) containing alternating mucic acid and charged monomers is synthesized. When combined with siRNA, cMAP forms NPs that require steric stabilization by poly(ethylene glycol) (PEG) that is attached to the NP surface via a 5-nitrophenylboronic acid linkage (5-nitrophenylboronic acid-PEGm (5-nPBA PEGm)) to diols on mucic acid in the cMAP in order to inhibit aggregation in biological fluids. As an alternative, cMAP is covalently conjugated with PEG via two methods. First, a copolymer is prepared with alternating cMAP-PEG units that can form loops of PEG on the surface of the formulated siRNA-containing NPs. Second, an mPEG-cMAP-PEGm triblock polymer is synthesized that could lead to a PEG brush configuration on the surface of the formulated siRNA-containing NPs. The copolymer and triblock polymer are able to form stable siRNA-containing NPs without and with the addition of 5-nPBA-PEGm. Five formulations, (i) cMAP with 5 nPBA-PEGm, (ii) cMAP-PEG copolymer both (a) with and (b) without 5-nPBA-PEGm, and (iii) mPEG-cMAP-PEGm triblock polymer both (a) with and (b) without 5-nPBA-PEGm, are used to produce NPs in the 30-40 nm size range, and their circulation times are evaluated in mice using tail vein injections. The mPEG-cMAP-PEGm triblock polymer provides the siRNA-containing NP with the longest circulation time (5-10% of the formulation remains in circulation at 60 min postdosing), even when a portion of the excess cationic components used in the formulation is filtered away prior to injection. A NP formulation using the mPEG-cMAP-PEGm triblock polymer that is free of excess components could contain as much as ca. 30 wt % siRNA. PMID- 26154103 TI - Single Chain Variable Fragments Produced in Escherichia coli against Heat-Labile and Heat-Stable Toxins from Enterotoxigenic E. coli. AB - BACKGROUND: Diarrhea is a prevalent pathological condition frequently associated to the colonization of the small intestine by enterotoxigenic Escherichia coli (ETEC) strains, known to be endemic in developing countries. These strains can produce two enterotoxins associated with the manifestation of clinical symptoms that can be used to detect these pathogens. Although several detection tests have been developed, minimally equipped laboratories are still in need of simple and cost-effective methods. With the aim to contribute to the development of such diagnostic approaches, we describe here two mouse hybridoma-derived single chain fragment variable (scFv) that were produced in E. coli against enterotoxins of ETEC strains. METHODS AND FINDINGS: Recombinant scFv were developed against ETEC heat-labile toxin (LT) and heat-stable toxin (ST), from previously isolated hybridoma clones. This work reports their design, construction, molecular and functional characterization against LT and ST toxins. Both antibody fragments were able to recognize the cell-interacting toxins by immunofluorescence, the purified toxins by ELISA and also LT-, ST- and LT/ST-producing ETEC strains. CONCLUSION: The developed recombinant scFvs against LT and ST constitute promising starting point for simple and cost-effective ETEC diagnosis. PMID- 26154104 TI - A Genome-Wide Association Study for Culm Cellulose Content in Barley Reveals Candidate Genes Co-Expressed with Members of the CELLULOSE SYNTHASE A Gene Family. AB - Cellulose is a fundamentally important component of cell walls of higher plants. It provides a scaffold that allows the development and growth of the plant to occur in an ordered fashion. Cellulose also provides mechanical strength, which is crucial for both normal development and to enable the plant to withstand both abiotic and biotic stresses. We quantified the cellulose concentration in the culm of 288 two--rowed and 288 six--rowed spring type barley accessions that were part of the USDA funded barley Coordinated Agricultural Project (CAP) program in the USA. When the population structure of these accessions was analysed we identified six distinct populations, four of which we considered to be comprised of a sufficient number of accessions to be suitable for genome-wide association studies (GWAS). These lines had been genotyped with 3072 SNPs so we combined the trait and genetic data to carry out GWAS. The analysis allowed us to identify regions of the genome containing significant associations between molecular markers and cellulose concentration data, including one region cross-validated in multiple populations. To identify candidate genes we assembled the gene content of these regions and used these to query a comprehensive RNA-seq based gene expression atlas. This provided us with gene annotations and associated expression data across multiple tissues, which allowed us to formulate a supported list of candidate genes that regulate cellulose biosynthesis. Several regions identified by our analysis contain genes that are co-expressed with cellulose synthase A (HvCesA) across a range of tissues and developmental stages. These genes are involved in both primary and secondary cell wall development. In addition, genes that have been previously linked with cellulose synthesis by biochemical methods, such as HvCOBRA, a gene of unknown function, were also associated with cellulose levels in the association panel. Our analyses provide new insights into the genes that contribute to cellulose content in cereal culms and to a greater understanding of the interactions between them. PMID- 26154105 TI - A novel TXNIP-based mechanism for Cx43-mediated regulation of oxidative drug injury. AB - Gap junctions (GJs) play an important role in the regulation of cell response to many drugs. However, little is known about their mechanisms. Using an in vitro model of cytotoxicity induced by geneticin (G418), we explored the potential signalling mechanisms involved. Incubation of cells with G418 resulted in cell death, as indicated by the change in cell morphology, loss of cell viability and activation of caspase-3. Before the onset of cell injury, G418 induced reactive oxygen species (ROS) generation, activated oxidative sensitive kinase P38 and caused a shift of connexin 43 (Cx43) from non-phosphorylated form to hyperphosphorylated form. These changes were largely prevented by antioxidants, suggesting an implication of oxidative stress. Downregulation of Cx43 with inhibitors or siRNA suppressed the expression of thioredoxin-interacting protein (TXNIP), activated Akt and protected cells against the toxicity of G418. Further analysis revealed that inhibition of TXNIP with siRNA activated Akt and reproduced the protective effect of Cx43-inhibiting agents, whereas suppression of Akt sensitized cells to the toxicity of G418. Furthermore, interference of TXNIP/Akt also affected puromycin- and adriamycin-induced cell injury. Our study thus characterized TXNIP as a presently unrecognized molecule implicated in the regulatory actions of Cx43 on oxidative drug injury. Targeting Cx43/TXNIP/Akt signalling cascade might be a promising approach to modulate cell response to drugs. PMID- 26154107 TI - Spectroelectrochemical Signatures of Capacitive Charging and Ion Insertion in Doped Anatase Titania Nanocrystals. AB - Solution-processed films of colloidal aliovalent niobium-doped anatase TiO2 nanocrystals exhibit modulation of optical transmittance in two spectral regions near-infrared (NIR) and visible light-as they undergo progressive and reversible charging in an electrochemical cell. The Nb-TiO2 nanocrystal film supports a localized surface plasmon resonance in the NIR, which can be dynamically modulated via capacitive charging. When the nanocrystals are charged by insertion of lithium ions, inducing a well-known structural phase transition of the anatase lattice, strong modulation of visible transmittance is observed. Based on X-ray absorption near-edge spectroscopy, the conduction electrons localize only upon lithium ion insertion, thus rationalizing the two modes of optical switching observed in a single material. These multimodal electrochromic properties show promise for application in dynamic optical filters or smart windows. PMID- 26154108 TI - Construction of a Urologic Robotic Surgery Training Curriculum: How Many Simulator Sessions Are Required for Residents to Achieve Proficiency? AB - PURPOSE: To define the time needed by urology residents to attain proficiency in computer-aided robotic surgery to aid in the refinement of a robotic surgery simulation curriculum. METHODS: We undertook a retrospective review of robotic skills training data acquired during January 2012 to December 2014 from junior (postgraduate year [PGY] 2-3) and senior (PGY4-5) urology residents using the da Vinci Skills Simulator. We determined the number of training sessions attended and the level of proficiency achieved by junior and senior residents in attempting 11 basic or 6 advanced tasks, respectively. RESULTS: Junior residents successfully completed 9.9 +/- 1.8 tasks, with 62.5% completing all 11 basic tasks. The maximal cumulative success rate of junior residents completing basic tasks was 89.8%, which was achieved within 7.0 +/- 1.5 hours of training. Of senior residents, 75% successfully completed all six advanced tasks. Senior residents attended 6.3 +/- 3.5 hours of training during which 5.1 +/- 1.6 tasks were completed. The maximal cumulative success rate of senior residents completing advanced tasks was 85.4%. CONCLUSION: When designing and implementing an effective robotic surgical training curriculum, an allocation of 10 hours of training may be optimal to allow junior and senior residents to achieve an acceptable level of surgical proficiency in basic and advanced robotic surgical skills, respectively. These data help guide the design and scheduling of a residents training curriculum within the time constraints of a resident's workload. PMID- 26154109 TI - Paramagnetic magnetization signals and curious metastable behaviour in field cooled magnetization of a single crystal of superconductor 2H-NbSe2. AB - We present here some newer characteristics pertaining to paramagnetic Meissner effect like response in a single crystal of the low [Formula: see text] superconducting compound 2H-[Formula: see text] via a detailed study of effects of perturbation on the field-cooled magnetization response. In the temperature range, where an anomalous paramagnetic magnetization occurs, the field-cooled magnetization response is found to be highly metastable: it displays a curious tendency to switch randomly from a given paramagnetic value to a diamagnetic or to a different paramagnetic value, when the system is perturbed by an impulse of an externally applied ac magnetic field. The new facets revealed in a single crystal of 2H-[Formula: see text] surprisingly bear a marked resemblance with the characteristics of magnetization behaviour anticipated for the giant vortex states with multiple flux quanta ([Formula: see text], [Formula: see text], [Formula: see text]) predicted to occur in mesoscopic-sized superconducting specimen and possible transitions amongst such states. PMID- 26154106 TI - Suicide Attempts in the US Army During the Wars in Afghanistan and Iraq, 2004 to 2009. AB - IMPORTANCE: The rate of suicide attempts in the US Army increased sharply during the wars in Afghanistan and Iraq. Research on this important health outcome has been hampered by the lack of integration among Army administrative data systems. OBJECTIVE: To identify risk factors for suicide attempts among active-duty members of the regular Army from January 1, 2004, through December 31, 2009. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, retrospective cohort study, as part of the Army Study to Assess Risk and Resilience in Servicemembers (STARRS), used individual-level person-month records from Army and Department of Defense administrative data systems to examine sociodemographic, service-related, and mental health predictors of medically documented suicide attempts among active-duty regular Army soldiers from January 1, 2004, through December 31, 2009. We analyzed data from 9791 suicide attempters and an equal-probability sample of 183,826 control person-months using a discrete-time survival framework. Data analysis was performed from February 3 through November 12, 2014. MAIN OUTCOMES AND MEASURES: Suicide attempts identified using Department of Defense Suicide Event Report records and diagnostic codes E950 through E958 from the International Classification of Diseases, Ninth Revision, Clinical Modification. Standardized estimates of suicide attempt risk for sociodemographic, service related, and mental health predictor variables were constructed from Army personnel and medical records. RESULTS: Enlisted soldiers accounted for 98.6% of all suicide attempts (9650 attempters; overall rate, 377.0 [95% CI, 369.7-384.7] per 100,000 person-years). In multivariate models, suicide attempts among enlisted soldiers were predicted (data reported as odds ratio [95% CI]) by female sex (2.4 [2.3-2.5]), entering Army service at 25 years or older (1.6 [1.5-1.8]), current age of 29 years or younger (<21 years, 5.6 [5.1-6.2]; 21-24 years, 2.9 [2.6-3.2]; 25-29 years, 1.6 [1.5-1.8]), white race (black, 0.7 [0.6-0.7]; Hispanic, 0.7 [0.7-0.8]; Asian, 0.7 [0.6-0.8]), an educational level of less than high school (2.0 [2.0-2.1]), being in the first 4 years of service (1-2 years, 2.4 [2.2-2.6]; 3-4 years, 1.5 [1.4-1.6]), having never (2.8 [2.6-3.0]) or previously (2.6 [2.4-2.8]) been deployed, and a mental health diagnosis during the previous month (18.2 [17.4-19.1]). Attempts among officers (overall rate, 27.9 per 100,000 person-years) were predicted by female sex (2.8 [2.0-4.1]), entering Army service at 25 years or older (2.0 [1.3-3.1]), current age of 40 years or older (0.5 [0.3-0.8]), and a mental health diagnosis during the previous month (90.2 [59.5-136.7]). Discrete-time hazard models indicated risk among enlisted soldiers was highest in the second month of service (102.7 per 100,000 person-months) and declined substantially as length of service increased (mean during the second year of service, 56.0 per 100,000 person-years; after 4 years of service, 29.4 per 100,000 person-months), whereas risk among officers remained stable (overall mean, 6.1 per 100,000 person-months). CONCLUSIONS AND RELEVANCE: Our results represent, to our knowledge, the most comprehensive accounting to date of suicide attempts in the Army. The findings reveal unique risk profiles for enlisted soldiers and officers and highlight the importance of research and prevention focused on enlisted soldiers in their first Army tour. PMID- 26154110 TI - Redox Conversion of Chromium(VI) and Arsenic(III) with the Intermediates of Chromium(V) and Arsenic(IV) via AuPd/CNTs Electrocatalysis in Acid Aqueous Solution. AB - Simultaneous reduction of Cr(VI) to Cr(III) and oxidation of As(III) to As(V) is a promising pretreatment process for the removal of chromium and arsenic from acid aqueous solution. In this work, the synergistic redox conversion of Cr(VI) and As(III) was efficiently achieved in a three-dimensional electrocatalytic reactor with synthesized AuPd/CNTs particles as electrocatalysts. The AuPd/CNTs facilitated the exposure of active Pd{111} facets and possessed an approximate two-electron-transfer pathway of oxygen reduction with the highly efficient formation of H2O2 as end product, resulting in the electrocatalytic reduction of 97.2 +/- 2.4% of Cr(VI) and oxidation of 95.7 +/- 4% of As(III). The electrocatalytic reduction of Cr(VI) was significantly accelerated prior to the electrocatalytic oxidation of As(III), and the effectiveness of Cr(VI)/As(III) conversion was favored at increased currents from 20 to 150 mA, decreased initial pH from 7 to 1 and concentrations of Cr(VI) and As(III) ranging from 50 to 1 mg/L. The crucial intermediates of Cr(V) and As(IV) and active free radicals HO(*) and O2(*-) were found for the first time, whose roles in the control of Cr(VI)/As(III) redox conversion were proposed. Finally, the potential applicability of AuPd/CNTs was revealed by their stability in electrocatalytic conversion over 10 cycles. PMID- 26154111 TI - Association study of single nucleotide polymorphisms in JAK2 and STAT5B genes and their differential mRNA expression with mastitis susceptibility in Chinese Holstein cattle. AB - The JAK-STAT pathway plays a key role in mediating immune responses. The genetic effects of single nucleotide polymorphisms (SNPs) in JAK2 and STAT5B were investigated for serum cytokines, mastitis indicators and productions traits in a population of 468 Chinese Holstein cattle. Pooled DNA sequencing revealed one SNP (BTA8:g.39645396A>G) in JAK2 and two SNPs (BTA19:g.43673888A>G and BTA19:g.43660093T>C) in STAT5B. A fixed effect model considering the effects of SNPs, parity, herd, season and year of calving was used by way of the general linear model procedure of sas. Genotype frequencies of these SNPs in the population were in Hardy-Weinberg equilibrium (P > 0.05). A novel SNP (g.39645396A>G) in JAK2 was predicted to change the amino acid from lysine to asparagine and was significantly associated with the somatic cell count (SCC) and somatic cell score (SCS), whereas g.43673888A>G in STAT5B was significantly associated with SCC, SCS and interleukin-4 (IL-4) (P < 0.05). The dominant effect of g.39645396A>G in JAK2 was significant for SCS, and its additive effect was significant for SCC, whereas the dominant effect of g.43673888A>G in STAT5B was significant for SCS and IL-4 (P < 0.05). The combination of g.39645396A>G in JAK2 and g.43673888A>G in STAT5B showed a significant effect on SCC, SCS, IL-4 and TNF alpha (P < 0.05). As for mRNA expression analysis, the AA genotype g.39645396A>G and GG genotype g.43673888A>G indicated higher mRNA expression level and were significantly different from other genotypes (P < 0.05). The results imply that JAK2 and STAT5B genes could be useful candidate genes, and the identified polymorphisms might potentially be strong genetic markers for selection of dairy cattle against mastitis development. PMID- 26154112 TI - Choroidal Thickness in Patients with Systemic Lupus Erythematosus Analyzed by Spectral-domain Optical Coherence Tomography. AB - PURPOSE: The aim of this study is to investigate the effect of systemic lupus erythematosus (SLE) on choroidal thickness (CT) in the subfoveal and perifoveal area as measured by enhanced depth imaging optical coherence tomography (EDI-OCT) in patients with SLE. MATERIALS AND METHODS: Fifty-eight patients with SLE (study group) and 58 healthy individuals (control group) were enrolled in the study. The subfoveal and perifoveal CT were measured by EDI-OCT. RESULTS: The mean CT (MUm) subfoveal, nasal, and temporal was 231.2 +/- 57.6, 190.56 +/- 30.64, and 222.65 +/- 37.45 in the study group and 297.5 +/- 45.1, 248.34 +/- 39.67, and 286.54 +/- 49.65 in the control group, respectively (p < 0.001, for all). CONCLUSION: The mean subfoveal, nasal, and temporal CT values were statistically significantly lower in patients with SLE when compared with healthy controls. PMID- 26154113 TI - Light Effect on Water Viscosity: Implication for ATP Biosynthesis. AB - Previous work assumed that ATP synthase, the smallest known rotary motor in nature, operates at 100% efficiency. Calculations which arrive to this result assume that the water viscosity inside mitochondria is constant and corresponds to that of bulk water. In our opinion this assumption is not satisfactory for two reasons: (1) There is evidence that the water in mitochondria prevails to 100% as interfacial water. (2) Laboratory experiments which explore the properties of interfacial water suggest viscosities which exceed those of bulk water, specifically at hydrophilic interfaces. Here, we wish to suggest a physicochemical mechanism which assumes intramitochondrial water viscosity gradients and consistently explains two cellular responses: The decrease and increase in ATP synthesis in response to reactive oxygen species and non destructive levels of near-infrared (NIR) laser light, respectively. The mechanism is derived from the results of a new experimental method, which combines the technique of nanoindentation with the modulation of interfacial water layers by laser irradiation. Results, including the elucidation of the principle of light-induced ATP production, are expected to have broad implications in all fields of medicine. PMID- 26154114 TI - Development of reconstitutable suspensions containing diclofenac sodium-loaded microspheres for pediatric delivery. AB - Effective clinical utilisation of non-steroidal anti-inflammatory drugs, such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration. The objective of this work was to develop reconstitutable pediatric suspensions of DS-loaded microspheres prepared with an acrylic polymer (Eudragit RS) for improved pediatric delivery of DS. The microspheres were prepared by the water-in-oil-in-water or solid-in-oil in-water emulsion techniques. Enviromental scanning electron microscopy observations clearly showed that microspheres have spherical shape. The drug entrapment efficiency of these microspheres was found 47.96 +/- 0.79% to 88.57 +/ 0.59% and their average particle sizes were 23.94-60.78 um, which are within the desired range for the development of suspension formulation. The in vitro dissolution indicated prolonged sustained release of DS over 8 h. The results of preliminary characterisation studies of suspensions show that a liquid pharmaceutical preparation for oral administration capable of providing a sustained release of DS was successfully obtained. PMID- 26154115 TI - Knowing is not Enough. PMID- 26154116 TI - In Pursuit of Professional Perfectionism. PMID- 26154117 TI - The Development of Evidence Briefs to Transfer Knowledge About Advanced Practice Nursing Roles to Providers, Policymakers and Administrators. AB - The transfer of health-related research knowledge between producers and users is a complex, dynamic and iterative process. There has been little research describing the preferred knowledge transfer strategies used by different stakeholder groups, including healthcare providers, policymakers and administrators. The purpose of the survey was to gain an understanding of the content and preferred dissemination strategies of knowledge users of briefing notes about the effectiveness of advanced practice nursing (APN) roles in Canada. An on-line cross-sectional survey was conducted from December 2011 to January 2012. Purposeful sampling was used to identify the target audience. The questionnaire included six items. The response rate was 44% (n=75/170). Participants identified that the briefing note should concisely summarize definitions for APN roles and information about the safety, effectiveness, cost savings and effective role implementation strategies. Multiple approaches were favoured to disseminate the information. Preferred dissemination strategies included personalized emails, meeting with briefing note recipients, engaging nurse practitioners and clinical nurse specialists in organizations where APN roles have been successfully implemented, engaging the media and using social media. The use of briefing notes has shown promise. More research is needed to evaluate the effectiveness of tailored briefing notes. PMID- 26154118 TI - Should Nurses Be Knowledge Brokers? Competencies and Organizational Resources to Support the Role. AB - Registered nurses with graduate preparation are in a unique position to act as knowledge brokers owing to their extensive clinical experience and ability to be seen as a credible and respected resource by their peers. Nurse knowledge brokers can bridge the gap between research producers and those that need evidence for decision-making and support capacity development for evidence-informed decision making (EIDM). Knowledge broker competencies include graduate-level education with exposure to research methods; experience with the EIDM process; and established networking skills to bring researchers, decision-makers, stakeholders and policymakers together. For the knowledge broker to be successful, the nurse leader can cultivate an organizational culture supportive of evidence use with advocacy for mandates that require evidence for decisions, structures in place for each stage of the EIDM process, and physical resources such as library services for evidence retrieval. PMID- 26154119 TI - Calling All Nurses and Nursing Leaders: How Do "You" Get Knowledge into Practice? Is a Broker the Answer? PMID- 26154120 TI - Financial Recruitment Incentive Programs for Nursing Personnel in Canada. AB - Financial incentives are increasingly offered to recruit nursing personnel to work in underserved communities. The authors describe and compare the characteristics of federal, provincial and territorial financial recruitment incentive programs for registered nurses (RNs), nurse practitioners (NPs), licensed practical nurses (LPNs), registered practical nurses or registered psychiatric nurses. The authors identified incentive programs from government, health ministry and student aid websites and by contacting program officials. Only government-funded recruitment programs providing funding beyond the normal employee wages and benefits and requiring a service commitment were included. The authors excluded programs offered by hospitals, regional or private firms, and programs that rewarded retention. All provinces and territories except QC and NB offer financial recruitment incentive programs for RNs; six provinces (BC, AB, SK, ON, QC and NL) offer programs for NPs, and NL offers a program for LPNs. Programs include student loan forgiveness, tuition forgiveness, education bursaries, signing bonuses and relocation expenses. Programs target trainees, recent graduates and new hires. Funding and service requirements vary by program, and service requirements are not always commensurate with funding levels. This snapshot of government-funded recruitment incentives provides program managers with data to compare and improve nursing workforce recruitment initiatives. PMID- 26154121 TI - Leadership, Education and Awareness: A Compassionate Care Nursing Initiative. AB - The Canadian Nurses' Association Code of Ethics (2008) and the College of Registered Nurses of Nova Scotia (CRNNS) Standards of Practice for Registered Nurses (CRNNS 2011) identify the provision of safe, compassionate, competent and ethical care as one of nursing's primary values and ethical responsibilities. While compassion has historically been viewed as the essence of nursing, there is concern that this has become an abstract ideal, rather than a true reflection of nursing practice. This paper describes a compassionate care initiative undertaken by the CRNNS and the initial outcomes of these educational workshops. This work is informed by an exploration of the multiplicity of factors that have brought this issue to the fore for nursing regulators, educators, administrators, the public as well as front-line staff. The two most significant areas of learning reported by workshop participants included understanding the connection between mindfulness, non-judgmental care and compassion/self-compassion and recognizing possibilities for action related to compassionate care, even in the face of personal and environmental constraints. Implications for nursing regulators and leaders include consideration of their roles and responsibilities in supporting nurses to meet professional practice standards, such as provision of compassionate care. PMID- 26154122 TI - Leading the Way: Implementing a Domestic Violence Assessment Pilot Project by Public Health Nurses. AB - The current healthcare system requires nurses to utilize innovations and effective leadership to achieve positive health outcomes for their patients. Public health nurses (PHNs) are in a unique position to utilize leadership and advocacy to increase the overall health and well-being of their clients. Domestic violence (DV) is a serious and widespread public health issue and PHNs have a crucial role in providing a preventative and coordinated approach to identifying and responding to DV. This article describes the process through which a group of front line PHNs took an active role in leading the development and implementation of a pilot project to address DV within their practice area. Through the development of a working group, a foundation for guidance was established to reinforce the role of the PHNs in advocating for the need to shift the focus of DV interventions from a reactive to a proactive approach. The DV assessment pilot project is an example for practice and a motivator for nurses to be leaders for change within their practice areas. PMID- 26154123 TI - Transforming Community Access Services through Client- and Family-Centred Homecare Transitions. AB - This article describes how one provincial health region adopted a client- and family-centred approach to improve access to community health services. Transition best practices and the "Triple Aim" supplied a framework for the transformation of transition of clients needing home healthcare services (Berwick et al. 2008). The need to improve the patient and family experience, establish and streamline professional practice standards, strengthen interprofessional collaborations, increase efficiency, create a critical mass of experts in the clinical domain of care transitions and program access, and evaluate customer experience were the organizational drivers for this transformation. The new framework identifies clients' needs and assigns a priority code. It also identifies which family member provides what support to the client and offers a one-stop service number staffed by individuals trained to provide client- and family-centred homecare services. This transformation of home healthcare transitions has improved the client and family experience, strengthened service provider satisfaction and generated efficiencies in prioritizing and delivering community healthcare services. PMID- 26154124 TI - In vitro and in silico toxicity evaluation of bioactive 4'-aminochalcone derivatives. AB - The 4'-aminochalcones compounds are open-chain flavonoids structures which have shown a known array of pharmacological activities, such as antibacterial, antifungal, anti-inflammatory and antitumor effects. There is little toxicological information available about these compounds in the literature. Therefore, the investigation of toxic effects of three 4'-aminochalcone derivatives was performed using in silico and in vitro assays. In silico provided results that indicated the occurrence of mutagenic and genotoxic effects. In vitro tests, using Cellular Proliferation and Viability, Micronucleus, and DNA damage by Comet assay, showed that the compounds studied also present mutagenic and genotoxic effects, which confirm the result determined by the in silico analysis. The use of experimental and computational models is complementary to each other and the results determined for 4'-aminochalones suggest that the chalcones should also be carefully considered since they show some risks to cause toxic effects to human cells. PMID- 26154125 TI - Chloroquine rescues A549 cells from paraquat-induced death. AB - Paraquat (PQ) is a widely used herbicide associated with a high mortality rate, yet, there are no effective treatments for PQ poisoning. PQ may damage alveolar type II cells leading to moderate to severe acute respiratory distress syndrome (ARDS). The present study was undertaken to show that PQ causes alveolar type II (A549) cell death and to evaluate whether chloroquine (CQ) can protect A549 cells against PQ-induced cell death. The results showed that high concentrations of PQ resulted in toxicity, as indicated by a decrease in cell viability. More importantly, for the first time, CQ was found to improve cell viability of PQ treated A549 cells. Moreover, our data demonstrated that CQ increased lysosome associated membrane protein-1, lysosome-associated membrane protein-2 and light chain-3 expressions, suggesting that the mechanism by which CQ rescues PQ-induced cytotoxicity may be through protection of the lysosomal membrane or up-regulation of autophagy. In conclusion, our study indicates that CQ may be used as a potential drug to rescue PQ-induced ARDS. PMID- 26154126 TI - Framework of barrier reefs threatened by ocean acidification. AB - To date, studies of ocean acidification (OA) on coral reefs have focused on organisms rather than communities, and the few community effects that have been addressed have focused on shallow back reef habitats. The effects of OA on outer barrier reefs, which are the most striking of coral reef habitats and are functionally and physically different from back reefs, are unknown. Using 5-m long outdoor flumes to create treatment conditions, we constructed coral reef communities comprised of calcified algae, corals, and reef pavement that were assembled to match the community structure at 17 m depth on the outer barrier reef of Moorea, French Polynesia. Communities were maintained under ambient and 1200 MUatm pCO2 for 7 weeks, and net calcification rates were measured at different flow speeds. Community net calcification was significantly affected by OA, especially at night when net calcification was depressed ~78% compared to ambient pCO2 . Flow speed (2-14 cm s(-1) ) enhanced net calcification only at night under elevated pCO2 . Reef pavement also was affected by OA, with dissolution ~86% higher under elevated pCO2 compared to ambient pCO2 . These results suggest that net accretion of outer barrier reef communities will decline under OA conditions predicted within the next 100 years, largely because of increased dissolution of reef pavement. Such extensive dissolution poses a threat to the carbonate foundation of barrier reef communities. PMID- 26154127 TI - Correction to Nanofilament Formation and Regeneration During Cu/Al2O3 Resistive Memory Switching. PMID- 26154129 TI - The Functional Role of PMP22 Gene in the Proliferation and Invasion of Osteosarcoma. AB - BACKGROUND: As the most common primary bone tumor, osteosarcoma has an improved survival rates with advancement of treatment methods. A higher rate of metastasis, however, leads to the aggravation of the disease. Studies have shown that some genes, namely osteosarcoma metastasis-related genes, participate in the process of tumor metastasis. The peripheral myelin protein 22 (PMP22) gene has recently been found to be abundantly expressed in the oncogenesis of osteosarcoma. Its detailed role and function in the tumor metastasis, however, remains unknown. MATERIAL AND METHODS: The recombinant retroviral plasmid pcDNA3.1-PMP22 was constructed and used to transfect osteosarcoma cells SOSP-M, whose cell proliferation was measured by MTT method. The formation of tumor cell colony, the cell migration and invasion were also measured. The signal transduction pathway MAPK was further analyzed by Western blotting. RESULTS: The pcDNA3.1-PMP22 plasmid was confirmed to have a 305bp PMP22 fragment by EcoRI-XhoI dual digestion. Compared to the control group, osteosarcoma cell invasion was significantly facilitated by the transfection of pcDNA3.1-PMP22 plasmid (p<0.05). The recombinant plasmid also significantly potentiated the formation of tumor cell colony and increased the migration and invasion ability of tumor cells (p<0.05 in all cases). Phosphorylated p-ERK and p-P38 were also up-regulated by vector transfection (p<0.05). CONCLUSIONS: Osteosarcoma metastasis-related gene PMP22 participates in the proliferation, invasion, migration and colony formation of osteosarcoma cells possibly via the MAPK signal transduction pathway, providing evidences for further investigation of metastatic mechanism of osteosarcoma. PMID- 26154128 TI - Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. AB - Pancreatic adenocarcinoma has the worst mortality of any solid cancer. In this study, to evaluate the clinical implications of genomic alterations in this tumour type, we perform whole-exome analyses of 24 tumours, targeted genomic analyses of 77 tumours, and use non-invasive approaches to examine tumour specific mutations in the circulation of these patients. These analyses reveal somatic mutations in chromatin-regulating genes MLL, MLL2, MLL3 and ARID1A in 20% of patients that are associated with improved survival. We observe alterations in genes with potential therapeutic utility in over a third of cases. Liquid biopsy analyses demonstrate that 43% of patients with localized disease have detectable circulating tumour DNA (ctDNA) at diagnosis. Detection of ctDNA after resection predicts clinical relapse and poor outcome, with recurrence by ctDNA detected 6.5 months earlier than with CT imaging. These observations provide genetic predictors of outcome in pancreatic cancer and have implications for new avenues of therapeutic intervention. PMID- 26154130 TI - [Traumatization and posttraumatic stress disorder. Effect of type and number of traumatic experiences]. AB - OBJECTIVE: The number and type of traumatic experiences show differential associations with posttraumatic stress disorder (PTSD). OBJECTIVE: The associations of number and type of traumatic experiences with PTSD were investigated in a representative population sample in Germany. MATERIAL AND METHODS: Traumatic experiences and PTSD were assessed with a self-rating questionnaire in a sample of 2510 participants from the general German population. RESULTS: The risk of (partial) PTSD increased with an increasing number of traumatic experiences. In contrast interpersonal and accidental traumatization showed no substantial differences with respect to the risk of PTSD. CONCLUSION: To quantify the relevance of the number and type of traumatic experiences for onset and persistence of PTSD, a multidimensional and complex assessment of those experiences is necessary. This is a great challenge in epidemiological research on this topic. PMID- 26154131 TI - What's inside your cat's head? A review of cat (Felis silvestris catus) cognition research past, present and future. AB - The domestic cat (Felis silvestris catus) has shared an intertwined existence with humans for thousands of years, living on our city streets and in our homes. Yet, little scientific research has focused on the cognition of the domestic cat, especially in comparison with human's other companion, the domestic dog (Canis lupus familiaris). This review surveys the current status of several areas of cat cognition research including perception, object permanence, memory, physical causality, quantity and time discrimination, cats' sensitivity to human cues, vocal recognition and communication, attachment bonds, personality, and cognitive health. Although interest in cat cognition is growing, we still have a long way to go until we have an inclusive body of research on the subject. Therefore, this review also identifies areas where future research must be conducted. In addition to the scientific value of future work in this area, future research on cat cognition could have an important influence on the management and welfare of pet and free-roaming cats, leading to improved human-cat interactions. PMID- 26154132 TI - Physical fitness, health behaviour and health among nursing students: A descriptive correlational study. AB - BACKGROUND: Health behaviour is of great importance for nursing students to achieve optimal health. Healthy students tend to complete their study and remain in the nursing workforce. They will also serve as a role model of for patients. However, there is limited research concerning physical fitness and health behaviour (such as sleep problems) in this population. OBJECTIVES: This study aims to examine the relationships among health behaviour, personal variables, physical fitness, perceived physical health and psychological health. DESIGN: A cross-sectional descriptive correlational study was used. PARTICIPANTS: A total of 335 nursing students who were enrolled in a university in Thailand. METHODS: Data were collected by self-administered questionnaires and physical fitness tests. Independent variables were personal variables and health behaviour. Outcome variables included physical fitness, perceived physical health and psychological health. Descriptive statistics and path analyses were used to analyse data. RESULTS: Nursing students had poor to moderate levels of total physical fitness, with cardiovascular fitness and body flexibility components having the lowest scores. Students who exercised regularly tended to have better physical fitness, perceived physical health and psychological health. Those who did not have sleep problems had better psychological health. CONCLUSION: Some personal variables and health behaviours were associated with health among nursing students. Appropriate interventions are required to promote positive health behaviour in this population. PMID- 26154134 TI - Fair Shares and Sharing Fairly: A Survey of Public Views on Open Science, Informed Consent and Participatory Research in Biobanking. AB - CONTEXT: Biobanks are important resources which enable large-scale genomic research with human samples and data, raising significant ethical concerns about how participants' information is managed and shared. Three previous studies of the Canadian public's opinion about these topics have been conducted. Building on those results, an online survey representing the first study of public perceptions about biobanking spanning all Canadian provinces was conducted. Specifically, this study examined qualitative views about biobank objectives, governance structure, control and ownership of samples and data, benefit sharing, consent practices and data sharing norms, as well as additional questions and ethical concerns expressed by the public. RESULTS: Over half the respondents preferred to give a one-time general consent for the future sharing of their samples among researchers. Most expressed willingness for their data to be shared with the international scientific community rather than used by one or more Canadian institutions. Whereas more respondents indicated a preference for one time general consent than any other model of consent, they constituted less than half of the total responses, revealing a lack of consensus among survey respondents regarding this question. Respondents identified biobank objectives, governance structure and accountability as the most important information to provide participants. Respondents' concerns about biobanking generally centred around the control and ownership of biological samples and data, especially with respect to potential misuse by insurers, the government and other third parties. Although almost half the respondents suggested that these should be managed by the researchers' institutions, results indicate that the public is interested in being well-informed about these projects and suggest the importance of increased involvement from participants. In conclusion, the study discusses the viability of several proposed models for informed consent, including e-governance, independent trustees and the use of exclusion clauses, in the context of these new findings about the views of the Canadian public. PMID- 26154133 TI - MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease. AB - Recent studies have found that extracellular vesicles (EVs) play an important role in normal and disease processes. In the present study, we isolated and characterized EVs from the brains of rhesus macaques, both with and without simian immunodeficiency virus (SIV) induced central nervous system (CNS) disease. Small RNA sequencing revealed increased miR-21 levels in EVs from SIV encephalitic (SIVE) brains. In situ hybridization revealed increased miR-21 expression in neurons and macrophage/microglial cells/nodules during SIV induced CNS disease. In vitro culture of macrophages revealed that miR-21 is released into EVs and is neurotoxic when compared to EVs derived from miR-21-/- knockout animals. A mutation of the sequence within miR-21, predicted to bind TLR7, eliminates this neurotoxicity. Indeed miR-21 in EV activates TLR7 in a reporter cell line, and the neurotoxicity is dependent upon TLR7, as neurons isolated from TLR7-/- knockout mice are protected from neurotoxicity. Further, we show that EVs isolated from the brains of monkeys with SIV induced CNS disease activates TLR7 and were neurotoxic when compared to EVs from control animals. Finally, we show that EV-miR-21 induced neurotoxicity was unaffected by apoptosis inhibition but could be prevented by a necroptosis inhibitor, necrostatin-1, highlighting the actions of this pathway in a growing number of CNS disorders. PMID- 26154135 TI - Clinical Implications of Noncaseating Granulomas on Histology in Patients with Ileal Pouches. AB - BACKGROUND: Granulomas are occasionally detected on biopsy specimen of the ileal pouch and their clinical implications are not clear. The aim of this study was to evaluate clinical implications of noncaseating granuloma on histology in patients with ileal pouches. METHODS: All eligible patients with confirmed noncaseating granulomas on histology of the biopsy specimens of the pouch body, afferent limb, or cuff in our prospectively maintained Pouch Registry between 2002 and 2014 were evaluated. Demographic and clinical factors were analyzed. The disease course of those patients was evaluated. RESULTS: Of 1564 patients in the Registry, 42 met the criteria and were included. The median duration from the pouch construction to the last visit was 9 years (range, 2-28 yr). Twenty-eight patients (66.7%) developed clinical Crohn's disease (CD) of the pouch, whereas 14 (33.3%) were classified as having histologic CD of the pouch. Six patients (21.4%) in the clinical CD of the pouch group and 4 (28.6%) in the histologic CD of the pouch group had granulomas on more than 1 endoscopy. Postoperative biological therapy was administered more in the clinical CD group than in the histologic CD group (39.3% versus 0%, P = 0.007). Pouch-related fistulae and presacral sinus were verified more in clinical CD group than the histologic CD group. However, Kaplan Meier plot showed comparable pouch survival between clinical CD and histologic CD groups. CONCLUSIONS: In our current study, one-third of the patients with noncaseating pouch granulomas did not develop clinical CD of the pouch. With proper medical therapy, long-term pouch outcomes appeared to be similar in those patients with clinical CD or histologic CD of the pouch. PMID- 26154137 TI - Body Fat Composition Predicts Infectious Complications After Bowel Resection in Crohn's Disease. PMID- 26154138 TI - Use of CT Scan in Ulcerative Colitis Patients Presenting to the Emergency Department. PMID- 26154136 TI - Extraintestinal Manifestations of Inflammatory Bowel Disease. AB - Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD. PMID- 26154139 TI - Analysis of Site Formation and Assemblage Integrity Does Not Support Attribution of the Uluzzian to Modern Humans at Grotta del Cavallo. AB - Based on the morphology of two deciduous molars and radiocarbon ages from layers D and E of the Grotta del Cavallo (Lecce, Italy), assigned to the Uluzzian, it has been proposed that modern humans were the makers of this Early Upper Paleolithic culture and that this finding considerably weakens the case for an independent emergence of symbolism among western European Neandertals. Reappraisal of the new dating evidence, of the finds curated in the Taranto Antiquities depot, and of coeval publications detailing the site's 1963-66 excavations shows that (a) Protoaurignacian, Aurignacian and Early Epigravettian lithics exist in the assemblages from layers D and E, (b) even though it contains both inherited and intrusive items, the formation of layer D began during Protoaurignacian times, and (c) the composition of the extant Cavallo assemblages is influenced in a non-negligible manner by the post-hoc assignment of items to stratigraphic units distinct from that of original discovery. In addition, a major disturbance feature affected the 1960s excavation trench down to Mousterian layer F, this feature went unrecognized until 1964, the human remains assigned to the Uluzzian were discovered that year and/or the previous year, and there are contradictions between field reports and the primary anthropological description of the remains as to their morphology and level of provenience. Given these major contextual uncertainties, the Cavallo teeth cannot be used to establish the authorship of the Uluzzian. Since this technocomplex's start date is ca. 45,000 calendar years ago, a number of Neandertal fossils are dated to this period, and the oldest diagnostic European modern human fossil is the <41,400 year-old Oase 1 mandible, Neandertal authorship of the Uluzzian remains the parsimonious reading of the evidence. PMID- 26154140 TI - Attomole-level Genomics with Single-molecule Direct DNA, cDNA and RNA Sequencing Technologies. AB - With the introduction of next-generation sequencing (NGS) technologies in 2005, the domination of microarrays in genomics quickly came to an end due to NGS's superior technical performance and cost advantages. By enabling genetic analysis capabilities that were not possible previously, NGS technologies have started to play an integral role in all areas of biomedical research. This chapter outlines the low-quantity DNA and cDNA sequencing capabilities and applications developed with the Helicos single molecule DNA sequencing technology. PMID- 26154142 TI - Paracrine CCL20 loop induces epithelial-mesenchymal transition in breast epithelial cells. AB - We previously found that CCL20 induced primarily cultured healthy breast cell proliferation and migration. The objective of this study was to investigate the hypothesis that CCL20 modulated the epithelial-mesenchymal transition (EMT) of primarily cultured healthy breast epithelial cells and the angiogenesis in areas adjacent to the tumor. Key results showed that CCL20 (a) down-regulated E cadherin and ZO-1; (b) up-regulated N-cadherin, vimentin, and Snail expressions; (c) increased mRNA and secretion of VEGF and (d) increased angiogenic micro vessel sprouting. Thus, the signal transduction pathways evoked by CCL20 were investigated. We showed that NF-kB p65 down-regulation (by small interfering RNA, siRNA) reversed CCL20-induced Snail and blocked the up-regulation of vimentin and N-cadherin mRNAs. Furthermore, PI3K/AKT inhibition (by LY294002) completely blocked CCL20-induced Snail and NF-kB activation. Inhibition of JNK1/2 (by SP60125) or PKC-alpha (by siRNA) or src (by PP1) blocked NF-kB activation and Snail expression suggesting that these kinases are all upstream of NF-kB/Snail. Inhibition of mTOR (by rapamycin) abolished the effects of CCL20 on N-cadherin and vimentin protein synthesis. Furthermore, siRNA of PKC-delta inhibited the phosphorylation of CCL20-induced mTOR and S6, increased vimentin and N-cadherin expressions and, finally, blocked the CCL20 induced-EMT. CCL20 increased mRNA and secretion of VEGF by healthy breast cells by using PKC-alpha, src, Akt, NF-kB, and Snail signalling. In summary, tumor cells signal to the surrounding healthy cells through CCL20 inducing the modulation of the expression of molecules involved in EMT and promoting angiogenesis directly and indirectly through the secretion of VEGF, a major contributor to angiogenesis. (c) 2015 Wiley Periodicals, Inc. PMID- 26154141 TI - The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice. AB - Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1beta levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition. PMID- 26154143 TI - Endoscopic cochlear implantation: Call for caution. AB - OBJECTIVES/HYPOTHESIS: To assess whether transcanal endoscopic access to the basal turn of the cochlea for cochlear implantation is appropriate. STUDY DESIGN: Case series study. METHODS: We reviewed 100 consecutive computed tomographic studies of the sinuses and temporal bone in our institution. We excluded studies that demonstrated evidence of congenital anomalies, chronic ear disease, or inadequate visualization of the cochlea. On axial sections, the angles of the basal turn of the cochlea and of the ear canal in reference to the sagittal plane were recorded as a function of age. RESULTS: Eighty-four studies were included and 16 were excluded. There was significant variability in the relationship between the ear canal and the basal turn of the cochlea in reference to the sagittal plane. A clear majority of images demonstrated the basal turn of the cochlea to align with a more posterior angle than that of the ear canal. CONCLUSION: The trajectory provided by posterior tympanotomy aligns more favorably with the basal turn of the cochlea than transcanal access. Endoscopic technique, primarily an ear canal intervention, may not be useful in cochlear implant surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:689-692, 2016. PMID- 26154144 TI - Genetic analysis of fat-to-protein ratio, milk yield and somatic cell score of Holstein cows in Japan in the first three lactations by using a random regression model. AB - We estimated the genetic parameters of fat-to-protein ratio (FPR) and the genetic correlations between FPR and milk yield or somatic cell score in the first three lactations in dairy cows. Data included 3,079,517 test-day records of 201,138 Holstein cows in Japan from 2006 to 2011. Genetic parameters were estimated with a multiple-trait random regression model in which the records within and between parities were treated as separate traits. The phenotypic values of FPR increased soon after parturition and peaked at 10 to 20 days in milk, then decreased slowly in mid- and late lactation. Heritability estimates for FPR yielded moderate values. Genetic correlations of FPR among parities were low in early lactation. Genetic correlations between FPR and milk yield were positive and low in early lactation, but only in the first lactation. Genetic correlations between FPR and somatic cell score were positive in early lactation and decreased to become negative in mid- to late lactation. By using these results for genetic evaluation it should be possible to improve energy balance in dairy cows. PMID- 26154145 TI - age of man. PMID- 26154146 TI - BRAF p.Val600Glu (V600E) mutation detection in thyroid fine needle aspiration cell block samples: a feasibility study. AB - Assessing BRAF mutation status in thyroid fine needle aspiration (FNA) cytology samples by both immunohistochemistry (IHC) and molecular methods has been documented in recent literature. We aim to highlight issues relating to quality and quantity of cellular material and DNA extracted from cell block samples.BRAF mutation status was assessed by both molecular and IHC methods in cell block material from thyroid FNA samples over a range of diagnostic categories, and correlated with available follow-up resection specimens.Of 39 samples there were 14 cases with 'inconclusive' cytology (Bethesda diagnostic categories 3, 4 or 5) and 25 cases with malignant cytology. Follow-up information was available in 38 of 39 cases and resection material for comparison in 18 of 39 case. Detection of BRAF mutation in cell block samples by combined molecular and IHC methods showed 100% specificity and 71.4% sensitivity compared to subsequent histologically confirmed BRAF mutated papillary thyroid carcinoma. IHC detected BRAF mutation in two (8.2%) cases which were negative by molecular methods and confirmed mutation positive by IHC and molecular methods on subsequent histology. Low extracted DNA concentration did not appear to preclude detection of BRAF mutation, although cell blocks with lower tumour cell content were over-represented in cases that were wild-type on FNA material and BRAF mutant on subsequent histology.BRAF mutation detection in cell block material is feasible and highly specific for papillary thyroid carcinoma. Best results are obtained by a combination of molecular and IHC methods. PMID- 26154147 TI - What is the indication for revision of malaligned paediatric supracondylar humerus fractures? PMID- 26154148 TI - Clinical and radiological outcomes of surgical treatment for symptomatic arachnoid cysts in adults. AB - We retrospectively analyzed 63 patients (31 males and 32 females) with arachnoid cysts managed over a 15 year period at our institution. Surgical indications and modalities for the treatment of intracranial arachnoid cysts are controversial, although endoscopic fenestration is often recommended as a standard procedure. In our cohort, clinical postoperative results and radiological assessments based on the presenting symptoms, cyst location, cyst volume and surgical modalities were recorded. The most common symptoms included headaches (66.7%), dizziness (46%) and seizures (36.5%). Cyst wall excision with microsurgical craniotomy was carried out in 28 patients (44.4%), cyst fenestration in 16 (25.4%), cystoperitoneal or ventriculoperitoneal shunting in 15 (23.8%) and endoscopic fenestration in four patients (6.3%). A satisfactory clinical outcome was achieved in 51 patients (80.9%) and cyst reduction was achieved in 49 (77.8%), at the last follow-up. Clinical improvement correlated significantly with volume reduction in patients with suprasellar and infratentorial cysts (r=0.495; p=0.022) while a similar result was not found after surgery in patients with frontal and temporal cysts. Surgical complications were not correlated with surgical modalities, occurring in only seven patients (11.1%). The various surgical modalities did not influence outcomes. Patients with nonspecific symptoms such as headache may obtain favourable outcomes from surgical treatment with no severe complications, although, intracranial hypertension and neurological deficits are more definite surgical indications for arachnoid cysts. PMID- 26154149 TI - Consistency of evoked responses to dual-stimulator, single-pulse transcranial magnetic stimulation in the lower limb of people with multiple sclerosis. AB - The purpose of this study was to explore the within session and test-retest consistency of motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) from the resting tibialis anterior (TA) muscle of 10 patients (two men, eight women) with clinically definite multiple sclerosis (MS). Dual stimulators were configured to produce a single pulse (DS/SP) through a hand-held coil. MEP were recorded in five blocks of five trials with a repeat test occurring 7-14 days later. Analysis of a trial sequence revealed the area of the first MEP trial of each block to be significantly different to subsequent trials (trials 2-5; p<0.05). We therefore discarded T1 from further analysis. Thereafter, repeated measures of analysis of variance of MEP characteristics and blocks of MEP (average of four trials) revealed no significant differences (p>0.05). The results of the repeat session revealed no significant differences in motor thresholds, MEP latency, MEP amplitude or MEP area between sessions (p>0.05). Test-retest intra-class coefficients of correlation and their 95% confidence intervals indicated high reliability (>0.80). Our results show that consistent, repeatable TMS measures can be obtained from the resting TA of MS patients using the DS/SP method. PMID- 26154150 TI - Nontraumatic spinal cord ischaemic syndrome. AB - This study presents the clinical features and functional outcomes of eight consecutive patients who were admitted to our institution between 2012 and 2014 with nontraumatic spinal cord infarction (SCI), a rare and devastating condition. We also present a literature review of aetiologies and prognostic factors relevant to our case series. The mean age of our cohort was 64 years and five patients were female. Aortic disease was causative in three, including one patient with biopsy confirmed giant cell arteritis. Fibrocartilaginous embolism was a possible aetiology in two others, anterior spinal artery aneurysm in one, and the cause was undetermined in two patients. American Spinal Injury Association impairment scale (ASIA) scores at nadir (time of maximum severity of signs) were B in three, C in three and D in two patients (all were wheelchair dependent). At last follow-up, ASIA scores were C in one, D in five and E in one patient. One patient died, two remained wheelchair dependent, four required a walking aid or frame and one was mobilising independently. A literature review of 11 patient series of nontraumatic SCI found that prognosis is primarily determined by the severity of motor or sensory involvement, in particular, initial and nadir ASIA A/B scores which strongly correlate with poor outcome. In the majority of series, 40-60% of patients had initial ASIA A/B scores with a similar proportion remaining wheelchair dependent on follow-up. Most patients in our cohort had nadir ASIA C/D scores, which may explain their better outcomes. PMID- 26154151 TI - A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression. AB - Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis. PMID- 26154153 TI - Quantification of the Demands During an Ice-Hockey Game Based on Intensity Zones Determined From the Incremental Test Outcomes. AB - The purpose of this study was to determine ice-hockey players' playing intensity based on their heart rates (HRs) recorded during a game and on the outcomes of an incremental maximum oxygen uptake test. Sixteen ice-hockey players, members of the Polish national team junior (U20), performed an incremental test to assess their maximal oxygen uptake (VO2max) in the 2 week's period preceding 4 games they played at the World Championships. Players' HRs at the first and second ventilatory thresholds obtained during the test were used to determine intensity zones (low, moderate, and high) that were subsequently used to classify HR values recorded during each of the games. For individual intensity zones, the following HRs expressed as mean values and as percentages of the maximal heart rate (HRmax) were obtained: forwards, 143-151 b . min(-1) (HRmax, 75.2-79.5%), 152-176 b . min(-1) (HRmax, 80.0-92.4%), 177-190 b . min(-1) (HRmax, 92.9-100.0%); defensemen, 127-139 b . min(-1) (HRmax, 69.4-75.8%), 140-163 b . min(-1) (HRmax, 76.4-89.0%), 164-184 b . min(-1) (HRmax, 89.5-100.0%). The amounts of time the forwards and defensemen spent in the 3 intensity zones expressed as percentages of the total time of the game were the following: 58.75% vs. 44.29% (low), 21.95% vs. 25.84% (moderate), and 19.30% vs. 29.87% (high). The forwards spent average more time in the low-intensity zone than did the defensemen, with the difference being statistically significant in periods 1 and 2 (61.44% vs. 44.21% at p <= 0.001 and 59.14% vs. 47.23% at p <= 0.01, respectively). The results of the study indicate that a method using aerobic and anaerobic metabolism parameters to determine intensity zones can significantly improve the reliability of evaluation of the physiological demands of the game and can be a useful tool for coaches in managing the training process. PMID- 26154152 TI - Signal transducer and activator of transcription 3-mediated CD133 up-regulation contributes to promotion of hepatocellular carcinoma. AB - Enhanced expression of the cancer stem cell (CSC) marker, CD133, is closely associated with a higher rate of tumor formation and poor prognosis in hepatocellular carcinoma (HCC) patients. Despite its clinical significance, the molecular mechanism underlying the deregulation of CD133 during tumor progression remains to be clarified. Here, we report on a novel mechanism by which interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling up-regulates expression of CD133 and promotes HCC progression. STAT3 activated by IL-6 rapidly bound to CD133 promoter and increased protein levels of CD133 in HCC cells. Reversely, in hypoxic conditions, RNA interference silencing of STAT3 resulted in decrease of CD133 levels, even in the presence of IL-6, with a concomitant decrease of hypoxia-inducible factor 1 alpha (HIF-1alpha) expression. Active STAT3 interacted with nuclear factor kappa B (NF-kappaB) p65 subunit to positively regulate the transcription of HIF-1alpha providing a mechanistic explanation on how those three oncogenes work together to increase the activity of CD133 in a hypoxic liver microenvironment. Activation of STAT3 and its consequent induction of HIF-1alpha and CD133 expression were not observed in Toll-like receptor 4/IL-6 double-knockout mice. Long-term silencing of CD133 by a lentiviral-based approach inhibited cancer cell-cycle progression and suppressed in vivo tumorigenicity by down-regulating expression of cytokinesis related genes, such as TACC1, ACF7, and CKAP5. We also found that sorafenib and STAT3 inhibitor nifuroxazide inhibit HCC xenograft formation by blocking activation of STAT3 and expression of CD133 and HIF-1alpha proteins. CONCLUSION: IL-6/STAT3 signaling induces expression of CD133 through functional cooperation with NF-kappaB and HIF-1alpha during liver carcinogenesis. Targeting STAT3 mediated CD133 up-regulation may represent a novel, effective treatment by eradicating the liver tumor microenvironment. PMID- 26154154 TI - Vascular Occlusion and Sequential Compression for Recovery After Resistance Exercise. AB - The purpose of this study was to evaluate vascular occlusion (OCC) and sequential intermittent pneumatic compression (SIPC) as recovery strategies after fatiguing resistance exercise. Twelve strength-trained male participants (age: 24.0 +/- 6.3 years, height: 180.4 +/- 9.7 cm, and weight: 84.8 +/- 9.6 kg) participated in a randomized cross-over study. Participants performed a fatiguing resistance exercise bout consisting of 10 sets with 10 repetitions of back squats at 70% 1 repetition maximum with 3-minute rest between sets. Outcome measures of perceived recovery status, muscle soreness, concentric peak isokinetic torque of the quadriceps, squat jump (SJ) height, and countermovement jump (CMJ) height were taken before the fatiguing resistance exercise bout and repeated immediately post, 1 hour, and 24 hours later. Immediately after the postexercise measures, participants undertook 1 of the 3 recovery strategies: OCC, SIPC, and a passive control (CON). Concentric peak isokinetic torque of the quadriceps was decreased significantly immediately post and 1 hour after the fatiguing resistance exercise bout compared with baseline values (p <= 0.05). Mean SJ and CMJ jump height decreased significantly immediately post and 1 hour compared with baseline measures, but only the SJ was significantly decreased at 24 hours. There were no significant differences between conditions for any of the postexercise measures (p > 0.05). In conclusion, this study indicates that OCC and SIPC are not effective for attenuating muscle performance loss after a fatiguing resistance exercise bout relative to passive recovery. PMID- 26154155 TI - Block-Periodized Training Improves Physiological and Tactically Relevant Performance in Naval Special Warfare Operators. AB - Human performance training and prevention strategies are necessary to promote physical readiness and mitigate musculoskeletal injuries of the Naval Special Warfare (NSW) Operator. The purpose of this study was to measure the effectiveness of 2 training programs when performed during a training evolution of Operators. A total of 85 Operators (experimental: n = 46, age: 29.4 +/- 5.5 years, height: 176.7 +/- 6.4 cm, mass: 86.7 +/- 11.6 kg; control: n = 39, age: 29.0 +/- 6.0 years, height: 177.1 +/- 6.3 cm, mass: 85.7 +/- 12.5 kg) participated in a trial to measure the effectiveness of these programs to improve physical, physiological, and performance characteristics. Operators in the experimental group performed a 12-week block-periodized program, whereas those in the control group performed a nonlinear periodized program. Pretesting/posttesting was performed to assess body composition, aerobic capacity/lactate threshold, muscular strength, flexibility, landing biomechanics, postural stability, and tactically relevant performance. The experimental group demonstrated a significant loss in body fat, fat mass, and body mass compared with the control group, whereas aerobic capacity increased for the both groups. The experimental group demonstrated a significant increase in posterior shoulder flexibility and ankle dorsiflexion, whereas the control group had a significant reduction in shoulder, knee, and ankle flexibility. The experimental group also improved landing strategies and balance. Both groups improved upper and lower muscular power and upper-body muscular endurance, whereas only the experimental group demonstrated significant improvements in agility and total body muscular strength. Implementation of a population-specific training program provides structured and progressive training effectively and promotes physical readiness concurrently with tactical training without overload. PMID- 26154156 TI - Anchorage onto deciduous teeth: effectiveness of early rapid maxillary expansion in increasing dental arch dimension and improving anterior crowding. AB - BACKGROUND: Anchorage onto permanent dentition is a common procedure in rapid maxillary expansion. However, replacing first permanent molars with the second deciduous molars seems to be an option to reduce some negative side effects during orthodontic treatment. The purpose of this study was to evaluate the dental effect of rapid maxillary expansion with anchorage exclusively onto deciduous teeth performed in the first period of transition. METHODS: Twenty patients with a lateral cross-bite treated exclusively by a Haas expander in early mixed dentition were retrospectively analyzed before treatment, at appliance removal, and at 21 months out of retention. The sagittal and transverse dimensions, together with the inter-canine arch and irregularity index, were digitally measured on scanned images of dental casts. The patients were compared with three balanced control groups (in total, 60 individuals) matched for gender. Two control groups had the same canine dental class as the treated group at T1, were in the inter-transitional period, and either had or lacked a lateral cross bite. The last control group was comprised of adolescents in permanent dentition with a dental class I. The statistical analysis was performed by means of repeated-measures ANOVA for paired data and one-way ANOVA, the Kruskal-Wallis test, and the Mann-Whitney test for independent measures (alpha-level p < 0.05). RESULTS: At the end of follow-up (inter-transitional period of dentition), the dental arch dimensions of treated patients were similar to those of adolescents with a dental class I and significantly wider than those of patients with a lateral cross-bite. Also, the anterior irregularity index was lower among patients who had undergone expansion treatments than in all untreated study participants. CONCLUSIONS: The Haas expander anchored to the deciduous teeth is effective in increasing the dental arch width in patients with a lateral cross bite. The dimensions of the dental arch were modified earlier toward the values of the permanent dentition. PMID- 26154158 TI - Dissociative Recombination of FeO(+) with Electrons: Implications for Plasma Layers in the Ionosphere. AB - The dissociative recombination (DR) of FeO(+) ions with electrons has been studied in a flowing afterglow reactor. FeO(+) was generated by the pulsed laser ablation of a solid Fe target, and then entrained in an Ar(+) ion/electron plasma where the absolute electron density was measured using a Langmuir probe. A kinetic model describing gas-phase chemistry and diffusion to the reactor walls was fitted to the experimental data, yielding a DR rate coefficient at 298 K of k(FeO(+) + e(-)) = (5.5 +/- 1.0) * 10(-7) cm(3) molecule(-1) s(-1), where the quoted uncertainty is at the 2sigma level. Fe(+) ions in the lower thermosphere are oxidized by O3 to FeO(+), and this DR reaction is shown to provide a more important route for neutralizing Fe(+) below 110 km than the radiative/dielectronic recombination of Fe(+) with electrons. The experimental system was first validated by measuring two other DR reaction rate coefficients: k(O2(+) + e(-)) = (2.0 +/- 0.4) * 10(-7) and k(N2O(+) + e(-)) = (3.3 +/- 0.8) * 10(-7) cm(3) molecule(-1) s(-1), which are in good agreement with the recent literature. PMID- 26154157 TI - Towards Automated Annotation of Benthic Survey Images: Variability of Human Experts and Operational Modes of Automation. AB - Global climate change and other anthropogenic stressors have heightened the need to rapidly characterize ecological changes in marine benthic communities across large scales. Digital photography enables rapid collection of survey images to meet this need, but the subsequent image annotation is typically a time consuming, manual task. We investigated the feasibility of using automated point annotation to expedite cover estimation of the 17 dominant benthic categories from survey-images captured at four Pacific coral reefs. Inter- and intra- annotator variability among six human experts was quantified and compared to semi and fully- automated annotation methods, which are made available at coralnet.ucsd.edu. Our results indicate high expert agreement for identification of coral genera, but lower agreement for algal functional groups, in particular between turf algae and crustose coralline algae. This indicates the need for unequivocal definitions of algal groups, careful training of multiple annotators, and enhanced imaging technology. Semi-automated annotation, where 50% of the annotation decisions were performed automatically, yielded cover estimate errors comparable to those of the human experts. Furthermore, fully-automated annotation yielded rapid, unbiased cover estimates but with increased variance. These results show that automated annotation can increase spatial coverage and decrease time and financial outlay for image-based reef surveys. PMID- 26154159 TI - Ultrasensitive ROS-Responsive Coassemblies of Tellurium-Containing Molecules and Phospholipids. AB - Reactive oxygen species (ROS) play crucial roles in cell signaling and redox homeostasis and are strongly related to metabolic activities. The increase of the ROS concentration in organisms can result in several diseases, such as cardiovascular diseases and cancer. The concentration of ROS in biologically relevant conditions is typically as low as around tens of micromolars to 100 MUM H2O2, which makes it necessary to develop ultrasensitive ROS-responsive systems. A general approach is reported here to fabricate an ultrasensitive ROS-responsive system via coassembly between tellurium-containing molecules and phospholipids, combining the ROS-responsiveness of tellurium and the biocompatibility of phospholipids. By using dynamic light scattering, transmission electron microscopy, scanning electron microscopy, and NMR spectra, coassembly behaviors and the responsiveness of the coassemblies have been investigated. These coassemblies can respond to 100 MUM H2O2, which is a biologically relevant ROS concentration, and demonstrate reversible redox properties. PMID- 26154160 TI - Cerium-based metal organic frameworks with UiO-66 architecture: synthesis, properties and redox catalytic activity. AB - A series of nine Ce(iv)-based metal organic frameworks with the UiO-66 structure containing linker molecules of different sizes and functionalities were obtained under mild synthesis conditions and short reaction times. Thermal and chemical stabilities were determined and a Ce-UiO-66-BDC/TEMPO system was successfully employed for the aerobic oxidation of benzyl alcohol. PMID- 26154161 TI - Use of a New High Resolution Melting Method for Genotyping Pathogenic Leptospira spp. AB - BACKGROUND: Leptospirosis is a worldwide zoonosis that is endemic in tropical areas, such as Reunion Island. The species Leptospira interrogans is the primary agent in human infections, but other pathogenic species, such as L. kirschner and L. borgpetersenii, are also associated with human leptospirosis. METHODS AND FINDINGS: In this study, a melting curve analysis of the products that were amplified with the primer pairs lfb1 F/R and G1/G2 facilitated an accurate species classification of Leptospira reference strains. Next, we combined an unsupervised high resolution melting (HRM) method with a new statistical approach using primers to amplify a two variable-number tandem-repeat (VNTR) for typing at the subspecies level. The HRM analysis, which was performed with ScreenClust Software, enabled the identification of genotypes at the serovar level with high resolution power (Hunter-Gaston index 0.984). This method was also applied to Leptospira DNA from blood samples that were obtained from Reunion Island after 1998. We were able to identify a unique genotype that is identical to that of the L. interrogans serovars Copenhageni and Icterohaemorrhagiae, suggesting that this genotype is the major cause of leptospirosis on Reunion Island. CONCLUSIONS: Our simple, rapid, and robust genotyping method enables the identification of Leptospira strains at the species and subspecies levels and supports the direct genotyping of Leptospira in biological samples without requiring cultures. PMID- 26154162 TI - Study on Enhancement Principle and Stabilization for the Luminol-H2O2-HRP Chemiluminescence System. AB - A luminol-H2O2-HRP chemiluminescence system with high relative luminescent intensity (RLU) and long stabilization time was investigated. First, the comparative study on the enhancement effect of ten compounds as enhancers to the luminol-H2O2-HRP chemiluminescence system was carried out, and the results showed that 4-(imidazol-1-yl)phenol (4-IMP), 4-iodophenol (4-IOP), 4-bromophenol (4-BOP) and 4-hydroxy-4'-iodobiphenyl (HIOP) had the best performance. Based on the experiment, the four enhancers were dissolved in acetone, acetonitrile, methanol, and dimethylformamide (DMF) with various concentrations, the results indicated that 4-IMP, 4-IOP, 4-BOP and HIOP dissolved in DMF with the concentrations of 0.2%, 3.2%, 1.6% and 3.2% could get the highest RLU values. Subsequently, the influences of pH, ionic strength, HRP, 4-IMP, 4-IOP, 4-BOP, HIOP, H2O2 and luminol on the stabilization of the luminol-H2O2-HRP chemiluminescence system were studied, and we found that pH value, ionic strength, 4-IMP, 4-IOP, 4-BOP, HIOP, H2O2 and luminol have little influence on luminescent stabilization, while HRP has a great influence. In different ranges of HRP concentration, different enhancers should be selected. When the concentration is within the range of 0~6 ng/mL, 4-IMP should be selected. When the concentration of HRP ranges from 6 to 25 ng/mL, 4-IOP was the best choice. And when the concentration is within the range of 25~80 ng/mL, HIOP should be selected as the enhancer. Finally, the three well-performing chemiluminescent enhanced solutions (CESs) have been further optimized according to the three enhancers (4-IMP, 4-IOP and HIOP) in their utilized HRP concentration ranges. PMID- 26154163 TI - Application of Genetic Algorithm to Predict Optimal Sowing Region and Timing for Kentucky Bluegrass in China. AB - Temperature is a predominant environmental factor affecting grass germination and distribution. Various thermal-germination models for prediction of grass seed germination have been reported, in which the relationship between temperature and germination were defined with kernel functions, such as quadratic or quintic function. However, their prediction accuracies warrant further improvements. The purpose of this study is to evaluate the relative prediction accuracies of genetic algorithm (GA) models, which are automatically parameterized with observed germination data. The seeds of five P. pratensis (Kentucky bluegrass, KB) cultivars were germinated under 36 day/night temperature regimes ranging from 5/5 to 40/40 degrees C with 5 degrees C increments. Results showed that optimal germination percentages of all five tested KB cultivars were observed under a fluctuating temperature regime of 20/25 degrees C. Meanwhile, the constant temperature regimes (e.g., 5/5, 10/10, 15/15 degrees C, etc.) suppressed the germination of all five cultivars. Furthermore, the back propagation artificial neural network (BP-ANN) algorithm was integrated to optimize temperature germination response models from these observed germination data. It was found that integrations of GA-BP-ANN (back propagation aided genetic algorithm artificial neural network) significantly reduced the Root Mean Square Error (RMSE) values from 0.21~0.23 to 0.02~0.09. In an effort to provide a more reliable prediction of optimum sowing time for the tested KB cultivars in various regions in the country, the optimized GA-BP-ANN models were applied to map spatial and temporal germination percentages of blue grass cultivars in China. Our results demonstrate that the GA-BP-ANN model is a convenient and reliable option for constructing thermal-germination response models since it automates model parameterization and has excellent prediction accuracy. PMID- 26154164 TI - Carryover Effects of Acute DEHP Exposure on Ovarian Function and Oocyte Developmental Competence in Lactating Cows. AB - We examined acute exposure of Holstein cows to di(2-ethylhexyl) phthalate (DEHP) and its carryover effects on ovarian function and oocyte developmental competence. Synchronized cows were tube-fed with water or 100 mg/kg DEHP per day for 3 days. Blood, urine and milk samples were collected before, during and after DEHP exposure to examine its clearance pattern. Ovarian follicular dynamics was monitored through an entire estrous cycle by ultrasonographic scanning. Follicular fluids were aspirated from the preovulatory follicles on days 0 and 29 of the experiment and analyzed for phthalate metabolites and estradiol concentration. The aspirated follicular fluid was used as maturation medium for in-vitro embryo production. Findings revealed that DEHP impairs the pattern of follicular development, with a prominent effect on dominant follicles. The diameter and growth rate of the first- and second-wave dominant follicles were lower (P < 0.05) in the DEHP-treated group. Estradiol concentration in the follicular fluid was lower in the DEHP-treated group than in controls, and associated with a higher number of follicular pathologies (follicle diameter >25 mm). The pattern of growth and regression of the corpus luteum differed between groups, with a lower volume in the DEHP-treated group (P < 0.05). The follicular fluid aspirated from the DEHP-treated group, but not the controls, contained 23 nM mono(2-ethylhexyl) phthalate. Culturing of cumulus oocyte complexes in the follicular fluid aspirated from DEHP-treated cows reduced the proportion of oocytes progressing to the MII stage, and the proportions of 2- to 4-cell-stage embryos (P < 0.04) and 7-day blastocysts (P < 0.06). The results describe the risk associated with acute exposure to DEHP and its deleterious carryover effects on ovarian function, nuclear maturation and oocyte developmental competence. PMID- 26154165 TI - From Peer-Reviewed to Peer-Reproduced in Scholarly Publishing: The Complementary Roles of Data Models and Workflows in Bioinformatics. AB - MOTIVATION: Reproducing the results from a scientific paper can be challenging due to the absence of data and the computational tools required for their analysis. In addition, details relating to the procedures used to obtain the published results can be difficult to discern due to the use of natural language when reporting how experiments have been performed. The Investigation/Study/Assay (ISA), Nanopublications (NP), and Research Objects (RO) models are conceptual data modelling frameworks that can structure such information from scientific papers. Computational workflow platforms can also be used to reproduce analyses of data in a principled manner. We assessed the extent by which ISA, NP, and RO models, together with the Galaxy workflow system, can capture the experimental processes and reproduce the findings of a previously published paper reporting on the development of SOAPdenovo2, a de novo genome assembler. RESULTS: Executable workflows were developed using Galaxy, which reproduced results that were consistent with the published findings. A structured representation of the information in the SOAPdenovo2 paper was produced by combining the use of ISA, NP, and RO models. By structuring the information in the published paper using these data and scientific workflow modelling frameworks, it was possible to explicitly declare elements of experimental design, variables, and findings. The models served as guides in the curation of scientific information and this led to the identification of inconsistencies in the original published paper, thereby allowing its authors to publish corrections in the form of an errata. AVAILABILITY: SOAPdenovo2 scripts, data, and results are available through the GigaScience Database: http://dx.doi.org/10.5524/100044; the workflows are available from GigaGalaxy: http://galaxy.cbiit.cuhk.edu.hk; and the representations using the ISA, NP, and RO models are available through the SOAPdenovo2 case study website http://isa-tools.github.io/soapdenovo2/. CONTACT: philippe.rocca-serra@oerc.ox.ac.uk and susanna-assunta.sansone@oerc.ox.ac.uk. PMID- 26154166 TI - Hydrogen Spillover between Single Gold Nanorods and Metal Oxide Supports: A Surface Plasmon Spectroscopy Study. AB - We used dark field spectroscopy to monitor the dissociation of hydrogen on single gold nanoparticles embedded in metal oxide supports. Individual gold nanorods were monitored in real time to reveal the peak position, the full width at half maximum, and the relative intensity of the surface plasmon resonances during repeated N2-H2-N2 and air-H2-air cycles. Shifts in the spectra are shown to be due to changes in electron density and not to refractive index shifts in the environment. We demonstrate that hydrogen does not dissociate on gold nanorods (13 nm * 40 nm) at room temperature when in contact with silica and that electrons or hydrogen atoms migrate from Pt nanoparticles to Au nanoparticles through the supporting metal oxide at room temperature. However, this spillover mechanism only occurs for semiconducting oxides (anatase TiO2 and ZnO) and does not occur for Au and Pt nanoparticles embedded in silica. Finally, we show that hydrogen does dissociate directly on anatase surfaces at room temperature during air-H2-air cycles. Our results show that hydrogen spillover, surface dissociation of reactants, and surface migration of chemical intermediates can be detected and monitored in real time at the single particle level. PMID- 26154168 TI - Can DNA-Based Ecosystem Assessments Quantify Species Abundance? Testing Primer Bias and Biomass--Sequence Relationships with an Innovative Metabarcoding Protocol. AB - Metabarcoding is an emerging genetic tool to rapidly assess biodiversity in ecosystems. It involves high-throughput sequencing of a standard gene from an environmental sample and comparison to a reference database. However, no consensus has emerged regarding laboratory pipelines to screen species diversity and infer species abundances from environmental samples. In particular, the effect of primer bias and the detection limit for specimens with a low biomass has not been systematically examined, when processing samples in bulk. We developed and tested a DNA metabarcoding protocol that utilises the standard cytochrome c oxidase subunit I (COI) barcoding fragment to detect freshwater macroinvertebrate taxa. DNA was extracted in bulk, amplified in a single PCR step, and purified, and the libraries were directly sequenced in two independent MiSeq runs (300-bp paired-end reads). Specifically, we assessed the influence of specimen biomass on sequence read abundance by sequencing 31 specimens of a stonefly species with known haplotypes spanning three orders of magnitude in biomass (experiment I). Then, we tested the recovery of 52 different freshwater invertebrate taxa of similar biomass using the same standard barcoding primers (experiment II). Each experiment was replicated ten times to maximise statistical power. The results of both experiments were consistent across replicates. We found a distinct positive correlation between species biomass and resulting numbers of MiSeq reads. Furthermore, we reliably recovered 83% of the 52 taxa used to test primer bias. However, sequence abundance varied by four orders of magnitudes between taxa despite the use of similar amounts of biomass. Our metabarcoding approach yielded reliable results for high-throughput assessments. However, the results indicated that primer efficiency is highly species-specific, which would prevent straightforward assessments of species abundance and biomass in a sample. Thus, PCR-based metabarcoding assessments of biodiversity should rely on presence-absence metrics. PMID- 26154167 TI - Direct Reprogramming of Human Primordial Germ Cells into Induced Pluripotent Stem Cells: Efficient Generation of Genetically Engineered Germ Cells. AB - Primordial germ cells (PGCs) share many properties with embryonic stem cells (ESCs) and innately express several key pluripotency-controlling factors, including OCT4, NANOG, and LIN28. Therefore, PGCs may provide a simple and efficient model for studying somatic cell reprogramming to induced pluripotent stem cells (iPSCs), especially in determining the regulatory mechanisms that fundamentally define pluripotency. Here, we report a novel model of PGC reprogramming to generate iPSCs via transfection with SOX2 and OCT4 using integrative lentiviral. We also show the feasibility of using nonintegrative approaches for generating iPSC from PGCs using only these two factors. We show that human PGCs express endogenous levels of KLF4 and C-MYC protein at levels similar to embryonic germ cells (EGCs) but lower levels of SOX2 and OCT4. Transfection with both SOX2 and OCT4 together was required to induce PGCs to a pluripotent state at an efficiency of 1.71%, and the further addition of C-MYC increased the efficiency to 2.33%. Immunohistochemical analyses of the SO-derived PGC-iPSCs revealed that these cells were more similar to ESCs than EGCs regarding both colony morphology and molecular characterization. Although leukemia inhibitory factor (LIF) was not required for the generation of PGC-iPSCs like EGCs, the presence of LIF combined with ectopic exposure to C-MYC yielded higher efficiencies. Additionally, the SO-derived PGC-iPSCs exhibited differentiation into representative cell types from all three germ layers in vitro and successfully formed teratomas in vivo. Several lines were generated that were karyotypically stable for up to 24 subcultures. Their derivation efficiency and survival in culture significantly supersedes that of EGCs, demonstrating their utility as a powerful model for studying factors regulating pluripotency in future studies. PMID- 26154169 TI - The hyper-sentient addict: an exteroception model of addiction. AB - BACKGROUND: Exteroception involves processes related to the perception of environmental stimuli important for an organism's ability to adapt to its environment. As such, exteroception plays a critical role in conditioned response. In addiction, behavioral and neuroimaging studies show that the conditioned response to drug-related cues is often associated with alterations in brain regions including the precuneus/posterior cingulate cortex, an important node within the default mode network dedicated to processes such as self monitoring. OBJECTIVE: This review aimed to summarize the growing, but largely fragmented, literature that supports a central role of exteroceptive processes in addiction. METHODS: We performed a systematic review of empirical research via PubMed and Google Scholar with keywords including 'addiction', 'exteroception', 'precuneus', and 'self-awareness', to identify human behavioral and neuroimaging studies that report mechanisms of self-awareness in healthy populations, and altered self-awareness processes, specifically exteroception, in addicted populations. RESULTS: Results demonstrate that exteroceptive processes play a critical role in conditioned cue response in addiction and serve as targets for interventions such as mindfulness training. Further, a hub of the default mode network, namely, the precuneus, is (i) consistently implicated in exteroceptive processes, and (ii) widely demonstrated to have increased activation and connectivity in addicted populations. CONCLUSION: Heightened exteroceptive processes may underlie cue-elicited craving, which in turn may lead to the maintenance and worsening of substance use disorders. An exteroception model of addiction provides a testable framework from which novel targets for interventions can be identified. PMID- 26154170 TI - Genome Wide Distributions and Functional Characterization of Copy Number Variations between Chinese and Western Pigs. AB - Copy number variations (CNVs) refer to large insertions, deletions and duplications in the genomic structure ranging from one thousand to several million bases in size. Since the development of next generation sequencing technology, several methods have been well built for detection of copy number variations with high credibility and accuracy. Evidence has shown that CNV occurring in gene region could lead to phenotypic changes due to the alteration in gene structure and dosage. However, it still remains unexplored whether CNVs underlie the phenotypic differences between Chinese and Western domestic pigs. Based on the read-depth methods, we investigated copy number variations using 49 individuals derived from both Chinese and Western pig breeds. A total of 3,131 copy number variation regions (CNVRs) were identified with an average size of 13.4 Kb in all individuals during domestication, harboring 1,363 genes. Among them, 129 and 147 CNVRs were Chinese and Western pig specific, respectively. Gene functional enrichments revealed that these CNVRs contribute to strong disease resistance and high prolificacy in Chinese domestic pigs, but strong muscle tissue development in Western domestic pigs. This finding is strongly consistent with the morphologic characteristics of Chinese and Western pigs, indicating that these group-specific CNVRs might have been preserved by artificial selection for the favored phenotypes during independent domestication of Chinese and Western pigs. In this study, we built high-resolution CNV maps in several domestic pig breeds and discovered the group specific CNVs by comparing Chinese and Western pigs, which could provide new insight into genomic variations during pigs' independent domestication, and facilitate further functional studies of CNV associated genes. PMID- 26154171 TI - The Relationship between Runs of Homozygosity and Inbreeding in Jersey Cattle under Selection. AB - Inbreeding is often an inevitable outcome of strong directional artificial selection but on average it reduces population fitness with increased frequency of recessive deleterious alleles. Runs of homozygosity (ROH) representing genomic autozygosity that occur from mating between selected and genomically related individuals may be able to reveal the regions affecting fitness. To examine the influence of genomic autozygosity on fitness, we used a genome-wide association test to evaluate potential negative correlations between ROH and daughter pregnancy rate (DPR) or somatic cell score (SCS) in US Jersey cattle. In addition, relationships between changes of local ROH and inbreeding coefficients (F) were assessed to locate genomic regions with increased inbreeding. Despite finding some decreases in fertility associated with incremental increases in F, most emerging local ROH were not significantly associated with DPR or SCS. Furthermore, the analyses of ROH could be approximated with the most frequent haplotype(s), including the associations of ROH and F or traits. The analysis of the most frequent haplotype revealed that associations of ROH and fertility could be accounted for by the additive genetic effect on the trait. Thus, we suggest that a change of autozygosity is more likely to demonstrate footprints of selected haplotypes for production rather than highlight the possible increased local autozygosity of a recessive detrimental allele resulting from the mating between closely related animals in Jersey cattle. PMID- 26154173 TI - On the Potential of Surfers to Monitor Environmental Indicators in the Coastal Zone. AB - The social and economic benefits of the coastal zone make it one of the most treasured environments on our planet. Yet it is vulnerable to increasing anthropogenic pressure and climate change. Coastal management aims to mitigate these pressures while augmenting the socio-economic benefits the coastal region has to offer. However, coastal management is challenged by inadequate sampling of key environmental indicators, partly due to issues relating to cost of data collection. Here, we investigate the use of recreational surfers as platforms to improve sampling coverage of environmental indicators in the coastal zone. We equipped a recreational surfer, based in the south west United Kingdom (UK), with a temperature sensor and Global Positioning System (GPS) device that they used when surfing for a period of one year (85 surfing sessions). The temperature sensor was used to derive estimates of sea-surface temperature (SST), an important environmental indicator, and the GPS device used to provide sample location and to extract information on surfer performance. SST data acquired by the surfer were compared with data from an oceanographic station in the south west UK and with satellite observations. Our results demonstrate: (i) high quality SST data can be acquired by surfers using low cost sensors; and (ii) GPS data can provide information on surfing performance that may help motivate data collection by surfers. Using recent estimates of the UK surfing population, and frequency of surfer participation, we speculate around 40 million measurements on environmental indicators per year could be acquired at the UK coastline by surfers. This quantity of data is likely to enhance coastal monitoring and aid UK coastal management. Considering surfing is a world-wide sport, our results have global implications and the approach could be expanded to other popular marine recreational activities for coastal monitoring of environmental indicators. PMID- 26154172 TI - The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection. AB - BACKGROUND: Insertion of T4 lysozyme (T4L) into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed. METHODS: We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects. RESULTS: Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1) infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5. CONCLUSIONS: Our results suggest that recombinant CCR5 T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents. PMID- 26154174 TI - Transitioning to HIV Pre-Exposure Prophylaxis (PrEP) from Non-Occupational Post Exposure Prophylaxis (nPEP) in a Comprehensive HIV Prevention Clinic: A Prospective Cohort Study. AB - The uptake of pre-exposure prophylaxis (PrEP) for HIV prevention remains low. We hypothesized that a high proportion of patients presenting for HIV non occupational post-exposure prophylaxis (nPEP) would be candidates for PrEP based on current CDC guidelines. Outcomes from a comprehensive HIV Prevention Clinic are described. We evaluated all patients who attended the HIV Prevention Clinic for nPEP between January 1, 2013 and September 30, 2014. Each patient was evaluated for PrEP candidacy based on current CDC-guidelines and subjectively based on physician opinion. Patients were then evaluated for initiation of PrEP if they met guideline suggestions. Demographic, social, and behavioral factors were then analyzed with logistic regression for associations with PrEP candidacy and initiation. 99 individuals who attended the nPEP clinic were evaluated for PrEP. The average age was 32 years (range, 18-62), 83 (84%) were male, of whom 46 (55%) men who had have sex with men (MSM). 31 (31%) met CDC guidelines for PrEP initiation, which had very good agreement with physician recommendation (kappa=0.88, 0.78-0.98). Factors associated with PrEP candidacy included sexual exposure to HIV, prior nPEP use, and lack of drug insurance (p<0.05 for all comparisons). Combining nPEP and PrEP services in a dedicated clinic can lead to identification of PrEP candidates and may facilitate PrEP uptake. Strategies to ensure equitable access of PrEP should be explored such that those without drug coverage may also benefit from this effective HIV prevention modality. PMID- 26154175 TI - The Taxonomic and Phylogenetic Affinities of Bunopithecus sericus, a Fossil Hylobatid from the Pleistocene of China. AB - Fossil hylobatids are rare, but are known from late Miocene and Pleistocene sites throughout East Asia. The best-known fossil hylobatid from the Pleistocene of China is a left mandibular fragment with M2-3 (AMNH 18534), recovered from a pit deposit near the village of Yanjinggou in Wanzhou District, Chongqing Province. Matthew and Granger described this specimen in 1923 as a new genus and species, Bunopithecus sericus. Establishing the age of Bunopithecus has proved difficult because the Yanjinggou collection represents a mixed fauna of different ages, but it likely comes from early or middle Pleistocene deposits. Although the Bunopithecus specimen has featured prominently in discussions of hylobatid evolution and nomenclature, its systematic status has never been satisfactorily resolved. The present study reexamines the taxonomic and phylogenetic relationships of Bunopithecus by carrying out a detailed comparative morphometric study of its lower molars in relation to a large sample of modern hylobatids. Our results show that differences in M2 and M3 discriminate extant hylobatids fairly well, at least at the generic level, and that AMNH 18534 is not attributable to Hylobates, Nomascus or Symphalangus. Support for a close relationship between Bunopithecus and Hoolock is more equivocal. In most multivariate analyses, Bunopithecus presents a unique morphological pattern that falls outside the range of variation of any hylobatid taxon, although its distance from the cluster represented by extant hoolocks is relatively small. Our results support the generic distinction of Bunopithecus, which most likely represents an extinct crown hylobatid, and one that may possibly represent the sister taxon to Hoolock. PMID- 26154178 TI - Establishing A Therapeutic Climate for Geriatric Care. PMID- 26154176 TI - Can Walking or Biking to Work Really Make a Difference? Compact Development, Observed Commuter Choice and Body Mass Index. AB - OBJECTIVES: Promoting active commuting is viewed as one strategy to increase physical activity and improve the energy balance of more sedentary individuals thereby improving health outcomes. However, the potential effectiveness of promotion policies may be seriously undermined by the endogenous choice of commute mode. Policy to promote active commuting will be most effective if it can be demonstrated that 1) those in compact cities do not necessarily have a preference for more physical activity, and 2) that current active commuting is not explained by unobserved characteristics that may be the true source of a lower body mass index (BMI). METHODS: Daily time-use diaries are used in combination with geographical characteristics of where respondents live and work to test 1) whether residents of more compact settlements are characterized by higher activity levels; and 2) whether residents of more compact settlements are more likely to bike or walk to work. An endogenous treatment model of active commuting allows testing whether reductions in BMI associated with walking or biking to work are in fact attributable to that activity or are more strongly associated with unobserved characteristics of these active commuters. RESULTS: The analysis of general activity levels confirms that residents of more compact cities do not expend more energy than residents of more sprawling cities, indicating that those in compact cities do not necessarily have a preference for more physical activity. The endogenous treatment model is consistent with walking or biking to work having an independent effect on BMI, as unobserved factors that contribute to a higher likelihood of active commuting are not associated with lower BMI. CONCLUSIONS: Despite evidence that more compact settlement patterns enable active commuting, only a small share of workers in these areas choose to walk or bike to work. In general, the activity level of residents in more compact cities and residents in more sprawling areas is very similar. But, there is a robust association between active commuting and lower body mass index that is not explained by unobserved attributes or preferences suggests that policies to promote active commuting may be effective. In particular, active commuting has a greater effect on BMI. Consequently, compact settlement appears to be an effective infrastructure for promoting more active lifestyles. The policy challenge is finding ways to ensure that this infrastructure is more widely utilized. PMID- 26154179 TI - Determination of Structures and Energetics of Small- and Medium-Sized One-Carbon Bridged Twisted Amides using ab Initio Molecular Orbital Methods: Implications for Amidic Resonance along the C-N Rotational Pathway. AB - Twisted amides containing nitrogen at the bridgehead position are attractive practical prototypes for the investigation of the electronic and structural properties of nonplanar amide linkages. Changes that occur during rotation around the N-C(O) axis in one-carbon-bridged twisted amides have been studied using ab initio molecular orbital methods. Calculations at the MP2/6-311++G(d,p) level performed on a set of one-carbon-bridged lactams, including 20 distinct scaffolds ranging from [2.2.1] to [6.3.1] ring systems, with the C?O bond on the shortest bridge indicate significant variations in structures, resonance energies, proton affinities, core ionization energies, frontier molecular orbitals, atomic charges, and infrared frequencies that reflect structural changes corresponding to the extent of resonance stabilization during rotation along the N-C(O) axis. The results are discussed in the context of resonance theory and activation of amides toward N-protonation (N-activation) by distortion. This study demonstrates that one-carbon-bridged lactams-a class of readily available, hydrolytically robust twisted amides-are ideally suited to span the whole spectrum of the amide bond distortion energy surface. Notably, this study provides a blueprint for the rational design and application of nonplanar amides in organic synthesis. The presented findings strongly support the classical amide bond resonance model in predicting the properties of nonplanar amides. PMID- 26154177 TI - Face-n-Food: Gender Differences in Tuning to Faces. AB - Faces represent valuable signals for social cognition and non-verbal communication. A wealth of research indicates that women tend to excel in recognition of facial expressions. However, it remains unclear whether females are better tuned to faces. We presented healthy adult females and males with a set of newly created food-plate images resembling faces (slightly bordering on the Giuseppe Arcimboldo style). In a spontaneous recognition task, participants were shown a set of images in a predetermined order from the least to most resembling a face. Females not only more readily recognized the images as a face (they reported resembling a face on images, on which males still did not), but gave on overall more face responses. The findings are discussed in the light of gender differences in deficient face perception. As most neuropsychiatric, neurodevelopmental and psychosomatic disorders characterized by social brain abnormalities are sex specific, the task may serve as a valuable tool for uncovering impairments in visual face processing. PMID- 26154180 TI - Now that we're here, where are we? The JBI approach to evidence-based healthcare 20 years on. AB - Approaching almost 20 years of activity (and 10 years this year since the Joanna Briggs Institute, JBI, model of evidence-based healthcare was first published), the JBI remains one of the most successful international organizations to focus on the synthesis, transfer, and implementation of research evidence. Although similar in age and focus to the Cochrane Collaboration and other organizations of this nature, JBI has, from its inception, taken a broader view on what constitutes evidence to inform clinical decision making at the point of care and the need to be inclusive in order to answer the many different types of clinical and other care questions needing answers. The Institute published the JBI model of evidence-based healthcare 10 years ago this year, outlining a developmental framework of evidence-based practice that attempted to situate healthcare evidence and its role and use within the complexity of practice settings globally. Guidance on how to conduct reviews of different evidence types was limited at that time and has come a long way in the last decade. With a focus on both the scientific and pragmatic elements of the translational cycle, this article explores the history of methodological development of the Institute and postures where to from here. PMID- 26154181 TI - -295 T-to-C promoter region IL-16 gene polymorphism is associated with Whipple's disease. AB - Whipple's disease (WD) is a rare systemic condition caused, in genetically predisposed subjects, by Tropheryma whipplei, a common bacterium widespread in the environment. The relevance of genetic predisposition in WD is shown by the association with HLA alleles DRB1*13 and DQB1*06 and by the demonstration that, in patients with WD, the cytokine genetic profile is skewed toward a Th2 and Treg response. Since IL-16 is involved in hampering the development of a protective macrophagic response against Tropheryma whipplei, we investigated whether the genetic background of IL-16 is different between patients with WD and controls. The -295 T-to-C polymorphism of the promoter region of the IL-16 gene was studied in 90 patients with WD and 152 healthy controls. Levels of serum IL-16 protein were also tested. The frequency of the wild type T allele was significantly higher in patients with WD compared to the controls (155/180 vs. 235/304; p = 0.02 for the Chi(2) test), odds ratio 1.82 [95 % confidence interval (CI) 1.07 3.10]. The TT genotype was found in 65/90 patients with WD and 88/152 controls (p = 0.026). No relationship was found between serum levels of IL-16 and genotypes. Although the functional consequences of this genetic background on levels of IL 16 and on the course of the disease are still unknown, we found, for the first time, that the wild type T allele and the TT genotype of the -295 polymorphism are associated with WD. PMID- 26154182 TI - Flexibility in Bilingual Infants' Word Learning. AB - The present experiments tested bilingual infants' developmental narrowing for the interpretation of sounds that form words. These studies addressed how language specialization proceeds when the environment provides varied and divergent input. Experiment 1 (N = 32) demonstrated that bilingual 14- and 19-month-olds learned a pair of object labels consisting of the same syllable produced with distinct pitch contours (rising and falling). Infants' native languages did not use pitch contour to differentiate words. In Experiment 2 (N = 16), 22-month-old bilinguals failed to learn the labels. These results conflict with the developmental trajectory of monolinguals, who fail to learn pitch contour contrasts as labels at 17-19 months (Hay, Graf Estes, Wang, & Saffran, 2015). Bilingual infants exhibited a prolonged period of flexibility in their interpretation of potential word forms. PMID- 26154183 TI - Multiple Cutaneous Melanomas and Clinically Atypical Moles in a Patient With a Novel Germline BAP1 Mutation. AB - IMPORTANCE: Several kindreds having germline BAP1 mutations with a propensity for uveal and cutaneous melanomas and other internal malignancies have been described in an autosomal dominant tumor predisposition syndrome. However, clinically atypical moles have not been previously recognized as a component of this syndrome, to our knowledge. We describe the first kindred to date with a germline mutation in BAP1 associated with multiple cutaneous melanomas and classic dysplastic nevus syndrome. OBSERVATIONS: We describe a 53-year-old man who was initially seen in 2003 with dysplastic nevus syndrome, multiple atypical melanocytic proliferations showing loss of immunostaining for BAP1, and 7 cutaneous melanomas. Germline testing was performed in the proband, his 16-year old son, and his 13-year-old daughter, revealing a germline mutation in the BAP1 gene (c.592G>T, p.Glu198X) in the proband and in his 16-year-old son. CDKN2A and CDK4 genes were wild type. No members of this kindred reported a history of uveal melanoma. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first report of a patient with multiple melanomas, dysplastic nevus syndrome, and an inactivating germline BAP1 mutation. The coexistence of dysplastic nevus syndrome and a BAP1 germline mutation extends the spectrum of the BAP1 tumor predisposition syndrome and may confer a greater risk for cutaneous melanomas. PMID- 26154184 TI - A randomized crossover study comparing a novel needle guidance technology for simulated internal jugular vein cannulation. AB - BACKGROUND: Despite ultrasound guidance for central line placement, complications persist, as exact needle location is often difficult to confirm with standard two dimension ultrasound. A novel real-time needle guidance technology has recently become available (eZono, Germany) that tracks the needle during insertion. This randomized, blinded, crossover study examined whether this needle guidance technology improved cannulation of a simulated internal jugular (IJ) vein in an ultrasound phantom. METHODS: One hundred physicians were randomized to place a standard needle in an ultrasound neck phantom with or without the needle guidance system. Video cameras were placed externally and within the lumens of the vessels to record needle location in real time. The primary outcome measured was the rate of posterior wall puncture. Secondary outcomes included number of carotid artery punctures, number of needle passes, final needle position, time to cannulation, and comfort level with this new technology. RESULTS: The incidence of posterior vessel wall puncture without and with needle guidance was 49 and 13%, respectively (P < 0.001, odds ratio [OR] = 7.33 [3.44 to 15.61]). The rate of carotid artery puncture was higher without needle navigation technology than with needle navigation 21 versus 2%, respectively (P = 0.001, OR = 12.97 [2.89 to 58.18]). Final needle tip position being located within the lumen of the IJ was 97% accurate with the navigation technology and 76% accurate with standard ultrasound (P < 0.001, OR = 10.42 [2.76 to 40.0]). Average time for successful vessel cannulation was 1.37 times longer without guidance technology. CONCLUSION: This real-time needle guidance technology (eZono) shows significant improvement in needle accuracy and cannulation time during simulated IJ vein puncture. PMID- 26154185 TI - Ability of the nociception level, a multiparameter composite of autonomic signals, to detect noxious stimuli during propofol-remifentanil anesthesia. AB - BACKGROUND: A novel multidimensional index of nociception, the nociception level (NoL) index, derived from the nonlinear composite of heart rate (HR), HR variability, amplitude of the photoplethysmogram, skin conductance, fluctuations in skin conductance, and their time derivatives, was used to assess nociception during anesthesia. METHODS: Seventy-two American Society of Anesthesiologists I to III patients received propofol (target bispectral index, 45) and one of six remifentanil target concentrations in the range of 0 to 5 ng/ml. The NoL, mean arterial pressure (MAP; derived from a beat-to-beat finger cuff measurement), and HR were measured during nonnoxious, moderate noxious (skin incision), and intense noxious (intubation) stimulation. Values are represented as average (95% CI). RESULTS: NoL, HR, and MAP did not change during nonnoxious events. Incision increased HR by 1.3/min (-0.46 to 3.1/min; not significant), MAP by 7.9 mmHg ( 1.9 to 13.0 mmHg; not significant), and NoL by 8.0 (0.4 to 16.0; P < 0.001). Intubation increased HR by 7.0/min (1.4 to 12.0/min; P < 0.001), MAP by 13.0 mmHg (3.1 to 20 mmHg; P < 0.001), and NoL by 18.0 (7.8 to 29.0; P < 0.001). The DeltaNoL area under the curve (0.95) of the receiver operating characteristic curve was greater compared with DeltaHR (0.84, P < 0.001) and DeltaMAP (0.78, P < 0.001). Under nonnociceptive conditions, remifentanil had no effect on NoL, in contrast to HR and MAP that showed a dose-dependent decrease. CONCLUSIONS: The NoL is a reliable measure of moderate and intense noxious stimulation and outperforms HR and MAP in differentiating noxious from nonnoxious stimuli. In contrast to HR and MAP, the NoL was not affected by hemodynamic effects of remifentanil. PMID- 26154187 TI - Images in Anesthesiology: Massive Hepatic Parenchymal and Portal Venous Gas. PMID- 26154188 TI - Interaction of anticancer Ru(III) complexes with single stranded and duplex DNA model systems. AB - The interaction of the anticancer Ru(iii) complex AziRu - in comparison with its analogue NAMI-A, currently in advanced clinical trials as an antimetastatic agent - with DNA model systems, both single stranded and duplex oligonucleotides, was investigated using a combined approach, including absorption UV-vis spectroscopy, circular dichroism (CD) and electrospray mass spectrometry (ESI-MS) techniques. UV-vis absorption spectra of the Ru complexes were recorded at different times in a pseudo-physiological solution, to monitor the ligand exchange processes in the absence and in the presence of the examined oligonucleotides. CD experiments provided information on the overall conformational changes of the DNA model systems induced by these metal complexes. UV- and CD-monitored thermal denaturation studies were performed to analyse the effects of AziRu and NAMI-A on the stability of the duplex structures. ESI-MS experiments, carried out on the oligonucleotide/metal complex mixtures under investigation, allowed us to detect the formation of stable adducts between the guanine-containing oligomers and the ruthenium complexes. These data unambiguously demonstrate that both AziRu and NAMI-A can interact with the DNA model systems. Although very similar in their structures, the two metal compounds manifest a markedly different reactivity with the examined sequences, respectively, with either a naked Ru(3+) ion or a Ru(Im)(3+) (Im = imidazole) fragment being incorporated into the oligonucleotide structure via stable linkages. PMID- 26154190 TI - CORRIGENDA. PMID- 26154189 TI - Systematic characterization and simultaneous quantification of the multiple components of Rhododendron dauricum based on high-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry. AB - Rhododendron dauricum L. has been used as a traditional Chinese medicine to treat cough and asthma and relieve phlegm and bronchitis. In this study, a reliable method based on high-performance liquid chromatography with diode array detection and quadrupole time-of-flight tandem mass spectrometry was established to systematically identify and quantify the components in this herb for the first time. A total of 33 compounds were identified, including 24 flavonoids, six phenolic acids, two coumarins and one terpene. Among them, poriolin (17), farrerol-7-O-beta-d-glucopyranoside (20), and syzalterin (30) were isolated from this plant for the first time, and quercetin-3-beta-d-(6-p-hydroxy benzoyl) galactoside (19), quercetin-3-beta-d-(6-p-coumaroyl) galactoside (21), and myrciacetin (23) were identified from this genus for the first time. Fragmentation pathways of flavonoids also have been investigated by electrospray ionization mass spectrometry. Moreover, seven bioactive constituents, namely, gallic acid (1), scopoletin (6), dihydroquercetin (7), quercetin (22), kaempferol (25), 8-desmethyl farrerol (27), and farrerol (28), were simultaneously quantified. The developed method has been validated and applied to analyze ten samples of R. dauricum from Hebei Province successfully. The contents of the seven compounds have been detected and compared. PMID- 26154191 TI - Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency. AB - Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer's disease and Parkinson's disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency associated mechanisms under multiple pathological states. PMID- 26154192 TI - An experimental setup for traceable measurement and calibration of liquid flow rates down to 5 nl/min. AB - This work presents the improvements of an experimental setup for measuring ultra low flow rates down to 5 nl/min. The system uses a telecentric CCD imaging system mounted on a high-precision, computer-controlled linear stage to track a moving liquid meniscus inside a glass capillary. Compared to the original setup, the lowest attainable expanded uncertainty at any flow rate has been reduced from 5.4% to 2%. In addition, the conformity with specification of three commercial micro-fluidic devices was evaluated using the new setup: one syringe pump, one implantable infusion pump and one thermal flow sensor. The flow sensor and the implantable infusion pump met the compliance criteria (coverage probability 95%). The syringe pump however, failed to meet the specifications at 5 nl/min and 10 nl/min. No assessment could be made at higher flow rates. PMID- 26154193 TI - Rapid detection of Mmalton alpha1-antitrypsin deficiency allele by real-time PCR and melting curves in whole blood, serum and dried blood spot samples. AB - BACKGROUND: alpha1-Antitrypsin deficiency (AATD) is an autosomal codominant disorder associated with a high risk of developing lung and liver disease. The most common deficient alleles are known as Z and S. However, another deficient variant, called Mmalton, which causes a deficiency similar to variant Z, is considered to be the second cause of severe AATD in Spain. Nevertheless, the Mmalton allele is not recognizable by usual diagnostic techniques and therefore, its real prevalence is underestimated. We describe a rapid real-time PCR and melting curves assay designed for the detection of Mmalton AATD. METHODS: We tested the applicability of this new technique for the identification of the Mmalton allele in AATD screening using whole blood, dried blood spot (DBS) and serum samples. Mmalton heterozygote and homozygote samples and samples without this allele were included in the study. RESULTS: This new assay is able to detect homozygous and heterozygous genotypes in the same reaction and in a single step, giving matching results with those obtained by SERPINA1 gene sequencing. CONCLUSIONS: This technology is optimal for working with small amounts of DNA, such as in DBS and even with residual DNA present in serum samples, allowing improvement in routine algorithms of AATD diagnosis or large-scale screening. This method will be useful for obtaining more in depth knowledge of the real incidence of the Mmalton variant. PMID- 26154194 TI - Anti-streptavidin interferences in Roche thyroid immunoassays: a case report. PMID- 26154195 TI - Performance evaluation of low platelet count and platelet clumps detection on Mindray BC-6800 hematology analyzer. PMID- 26154196 TI - When fat becomes an ally of the enemy: adipose tissue as collaborator in human breast cancer. AB - Since the discovery of leptin in 1994, our vision of adipose tissue as a static organ regulating mainly lipid storage and release has been completely overthrown, and adipose tissue is now seen as an active and integral organ in human physiology. In the past years, extensive research has tremendously given us more insights in the mechanisms and pathways involved not only in normal but also in 'sick' adipose tissue, for example, in obesity and lipodystrophy. With growing evidence of a link between obesity and several types of cancer, research focusing on the interaction between adipose tissue and cancer has begun to unravel the interesting but complex multi-lateral communication between the different players. With breast cancer as one of the first cancer types where a positive correlation between obesity and breast cancer incidence and prognosis in post menopausal women was found, we have focused this review on the paracrine and endocrine role of adipose tissue in breast cancer initiation and progression. As important inter-species differences in adipose tissue occur, we mainly selected human adipose tissue- and breast cancer-based studies with a short reflection on therapeutic possibilities. This review is part of the special issue on "Adiposopathy in Cancer and (Cardio)Metabolic Diseases". PMID- 26154197 TI - Embedded 3D Photopatterning of Hydrogels with Diverse and Complex Architectures for Tissue Engineering and Disease Models. AB - Techniques that can create three-dimensional (3D) structures to provide architectural support for cells have a significant impact in generating complex and hierarchically organized tissues/organs. In recent times, a number of technologies, including photopatterning, have been developed to create such intricate 3D structures. In this study, we describe an easy-to-implement photopatterning approach, involving a conventional fluorescent microscope and a simple photomask, to encapsulate cells within spatially defined 3D structures. We have demonstrated the ease and the versatility of this approach by creating simple to complex as well as multilayered structures. We have extended this photopatterning approach to incorporate and spatially organize multiple cell types, thereby establishing coculture systems. Such cost-effective and easy-to use approaches can greatly advance tissue engineering strategies. PMID- 26154198 TI - Ergonomics and comfort in lawn mower handle positioning: An evaluation of handle geometry. AB - Hand operation accompanied with any combination of large forces, awkward positions and repetition may lead to upper limb injury or illness and may be exacerbated by vibration. Commercial lawn mowers expose operators to these factors during actuation of hand controls and therefore may be a health concern. A nontraditional lawn mower control system may decrease upper limb illnesses and injuries through more neutral hand and body positioning. This study compared maximum grip strength in twelve different orientations (3 grip spans and 4 positions) and evaluated self-described comfortable handle positions. The results displayed force differences between nontraditional (X) and both vertical (V) and pistol (P) positions (p < 0.0001) and among the different grip spans (p < 0.0001). Based on these results, recommended designs should incorporate a tilt between 45 and 70 degrees , handle rotations between 48 and 78 degrees , and reduced force requirements or decreased grip spans to improve user health and comfort. PMID- 26154199 TI - Efficacy of a rubber outsole with a hybrid surface pattern for preventing slips on icy surfaces. AB - Conventional winter-safety footwear devices, such as crampons, can be effective in preventing slips on icy surfaces but the protruding studs can lead to other problems such as trips. A new hybrid (rough and smooth) rubber outsole was designed to provide high slip resistance without use of protruding studs or asperities. In the present study, we examined the slip resistance of the hybrid rubber outsole on both dry (-10 degrees C) and wet (0 degrees C) icy surfaces, in comparison to three conventional strap-on winter anti-slip devices: 1) metal coils ("Yaktrax Walker"), 2) gritted (sandpaper-like) straps ("Rough Grip"), and 3) crampons ("Altagrips-Lite"). Drag tests were performed to measure static (SCOF) and dynamic (DCOF) coefficients of friction, and gait trials were conducted on both level and sloped ice surfaces (16 participants). The drag-test results showed relatively high SCOF (?0.37) and DCOF (?0.31) values for the hybrid rubber sole, at both temperatures. The other three footwear types exhibited lower DCOF values (0.06-0.20) when compared with the hybrid rubber sole at 0 degrees C (p < 0.01). Slips were more frequent when wearing the metal coils, in comparison to the other footwear types, when descending a slope at -10 degrees C (6% of trials vs 0%; p < 0.05). There were no other significant footwear-related differences in slip frequency, distance or velocity. These results indicate that the slip-resistance of the hybrid rubber sole on icy surfaces was comparable to conventional anti-slip footwear devices. Given the likely advantages of the hybrid rubber sole (less susceptibility to tripping, better slip resistance on non-icy surfaces), this type of sole should contribute to a decrease in fall accidents; however, further research is needed to confirm its effectiveness under a wider range of test conditions. PMID- 26154200 TI - Driver behaviour at roadworks. AB - There is an incompatibility between how transport engineers think drivers behave in roadworks and how they actually behave. As a result of this incompatibility we are losing approximately a lane's worth of capacity in addition to those closed by the roadworks themselves. The problem would have little significance were it not for the fact a lane of motorway costs approx. L30 m per mile to construct and L43 k a year to maintain, and that many more roadworks are planned as infrastructure constructed 40 or 50 years previously reaches a critical stage in its lifecycle. Given current traffic volumes, and the sensitivity of road networks to congestion, the effects of roadworks need to be accurately assessed. To do this requires a new ergonomic approach. A large-scale observational study of real traffic conditions was used to identify the issues and impacts, which were then mapped to the ergonomic knowledge-base on driver behaviour, and combined to developed practical guidelines to help in modelling future roadworks scenarios with greater behavioural accuracy. Also stemming from the work are novel directions for the future ergonomic design of roadworks themselves. PMID- 26154201 TI - Divide and rule: A qualitative analysis of the debriefing process in elite team sports. AB - This article aimed to gain an understanding of the process of debriefing during major competitions in elite team sports. Debrief interviews were conducted with 9 head coaches. The interview data were used to identify how head coaches divided up the tasks given to staff and team members prior to, and during the post-match debriefing. Results showed that debriefing consisted of two steps: preparation and presentation. Preparation referred to four successive tasks. Presentation to the team of players consisted of eight tasks relating to transformational and transactional styles of leadership. Coaches were shown to divide the labor within the staff and team. The data tend to support the view that in elite team sports, coaches are both transformational and transactional leaders, adapting their style of leadership to the situation, athletes and time available. This study provides insights into the task-work and team-work underlying team functioning and division of labor. PMID- 26154202 TI - Ergonomic evaluation of the operating characteristics of the 6MF-30 portable pneumatic extinguisher. AB - The 6MF-30 portable pneumatic extinguisher, which is one of the most widely used pieces of equipment for fighting forest fires in China, can produce great physical discomfort for the wearer. To mitigate the physical discomfort associated with the use of the 6MF-30, the operating characteristics of this machine were ergonomically evaluated. Fourteen subjects were instructed to operate the 6MF-30 portable pneumatic extinguisher using three different carrying postures (oblique strap, vertical strap and no strap) two different motions (stationary and swinging) during a simulated firefighting task. Dependent measures included heart rate (HR), electromyography (EMG) data and a subjective assessment (measured as the degree of fatigue in the left arm, right arm and waist). The EMG data were acquired from the palmaris longus and the biceps brachii of the left arm of each subject. Variance analysis indicated that the effects of the carrying posture on the HR (p < 0.001), the EMG data of the left arm (the p value of the palmaris longus is 0.001 and the p value of the biceps brachii is 0.015), and the degree of fatigue of the left and right arms (p < 0.001) were significant, while the effects of motion on all of the dependent measures, and the effects of carrying posture on the degree of fatigue of the waist were not significant. The effect of an oblique strap on the whole-body load is minimal, and the use of the equipment without a strap produced significantly greater physical discomfort for the wearer than did the oblique strap and the vertical strap. The results suggest that the strap of the 6MF-30 can help Chinese forest firefighters to lessen physical stress when operating the 6MF-30, and the use of the oblique strap should be adopted as the standard position. PMID- 26154203 TI - Effect of an auditory feedback substitution, tactilo-kinesthetic, or visual feedback on kinematics of pouring water from kettle into cup. AB - Pouring hot water from a kettle into a cup may prove a hazardous task, especially for the elderly or the visually-impaired. Individuals with deteriorating eyesight may endanger their hands by performing this task with both hands, relaying on tactilo-kinesthetic feedback (TKF). Auditory feedback (AF) may allow them to perform the task singlehandedly, thereby reducing the risk for injury. However since relying on an AF is not intuitive and requires practice, we aimed to determine if AF supplied during the task of pouring water can be used naturally as visual feedback (VF) following practice. For this purpose, we quantified, in young healthy sighted subjects (n = 20), the performance and kinematics of pouring water in the presence of three isolated feedbacks: visual, tactilo kinesthetic, or auditory. There were no significant differences between the weights of spilled water in the AF condition compared to the TKF condition in the first, fifth or thirteenth trials. The subjectively-reported difficulty levels of using the TKF and the AF were significantly reduced between the first and thirteenth trials for both TKF (p = 0.01) and AF (p = 0.001). Trunk rotation during the first trial using the TKF was significantly lower than the trunk rotation while using VF. Also, shoulder adduction during the first trial using the TKF was significantly higher than the shoulder adduction while using the VF. During the AF trials, the median travel distance of the tip of the kettle was significantly reduced in the first trials so that in the thirtieth trial it did not differ significantly from the median travel distance during the thirtieth trial using TKF and VF. The maximal velocity of the tip of the kettle was constant for each of the feedback conditions but was higher in 10 cm s(-1) using VF than TKF, which was higher in 10 cm s(-1) from using AF. The smoothness of movement of the TKF and AF conditions, expressed by the normalized jerk score (NJSM), was one and two orders of magnitude higher from the VF, respectively. The median NJSM then decreased significantly by the fifth trial. Monitoring in-house activity via motion capture and classification of movements, i.e. liquid pouring, can assist with daily activities via AF. As a built-in feature in a smart home, this task-specific AF may prevent burn injuries of the visually-impaired. PMID- 26154204 TI - Thermal environment in eight low-energy and twelve conventional Finnish houses. AB - We assessed the thermal environment of eight recently built low-energy houses and twelve conventional Finnish houses. We monitored living room, bedroom and outdoor air temperatures and room air relative humidity from June 2012 to September 2013. Perceived thermal environment was evaluated using a questionnaire survey during the heating, cooling and interim seasons. We compared the measured and perceived thermal environments of the low-energy and conventional houses. The mean air temperature was 22.8 degrees C (21.9-23.8 degrees C) in the low-energy houses, and 23.3 degrees C (21.4-26.5 degrees C) in the conventional houses during the summer (1. June 2013-31. August 2013). In the winter (1. December 2012-28. February 2013), the mean air temperature was 21.3 degrees C (19.8-22.5 degrees C) in the low-energy houses, and 21.6 degrees C (18.1-26.4 degrees C) in the conventional houses. The variation of the air temperature was less in the low energy houses than that in the conventional houses. In addition, the occupants were on average slightly more satisfied with the indoor environment in the low energy houses. However, there was no statistically significant difference between the mean air temperature and relative humidity of the low-energy and conventional houses. Our measurements and surveys showed that a good thermal environment can be achieved in both types of houses. PMID- 26154205 TI - The effectiveness of using pictures in teaching young children about burn injury accidents. AB - This study utilized the "story grammar" approach (Stein and Glenn, 1979) to analyze the within-corpus differences in recounting of sixty 6- and 7-year-old children, specifically whether illustrations (5-factor accident sequence) were or were not resorted to as a means to assist their narration of a home accident in which a child received a burn injury from hot soup. Our investigation revealed that the message presentation strategy "combining oral and pictures" better helped young children to memorize the story content (sequence of events leading to the burn injury) than "oral only." Specifically, the content of "the dangerous objects that caused the injury", "the unsafe actions that people involved took", and "how the people involved felt about the severity of the accident" differed significantly between the two groups. PMID- 26154206 TI - Applying riding-posture optimization on bicycle frame design. AB - Customization design is a trend for developing a bicycle in recent years. Thus, the comfort of riding a bike is an important factor that should be paid much attention to while developing a bicycle. From the viewpoint of ergonomics, the concept of "fitting object to the human body" is designed into the bicycle frame in this study. Firstly, the important feature points of riding posture were automatically detected by the image processing method. In the measurement process, the best riding posture was identified experimentally, thus the positions of feature points and joint angles of human body were obtained. Afterwards, according to the measurement data, three key points: the handlebar, the saddle and the crank center, were identified and applied to the frame design of various bicycle types. Lastly, this study further proposed a frame size table for common bicycle types, which is helpful for the designer to design a bicycle. PMID- 26154207 TI - Shoulder skin and muscle hemodynamics during backpack carriage. AB - The purpose of this study was to quantify the effects of loaded backpacks on shoulder muscle oxygenation, skin blood flow, and pain. We hypothesized that backpack load carriage is associated with lower shoulder muscle oxygenation and skin microvascular flow. Near-infrared spectroscopy quantified shoulder tissue oxygenation and laser Doppler flow measured skin microvascular flow. Eight adult volunteers donned a standard backpack without added load, 5 kg load, and 10 kg load for 5 min while standing. An 8 min rest period before each backpack donning condition ensured that all measured parameters returned to baseline. Data were analyzed using a repeated measures ANOVA and significance set at p < 0.05. Donning a 10 kg backpack significantly reduced shoulder muscle oxygenation by 22 +/- 23% as compared to the empty backpack control condition (p = 0.023). In addition, a 10 kg backpack load reduced skin microvascular flow by 82 +/- 22%, as compared to the empty backpack control condition (p = 0.024). Perceived pain was significantly higher when wearing the 10 kg backpack (level 4 on a 10-maximal pain scale) as compared to the empty backpack (0, 0-no pain) (p < 0.05). In conclusion, backpack loads of 10 kg decrease shoulder muscle oxygenation and skin microvascular flow. PMID- 26154208 TI - An ergonomics based design research method for the arrangement of helicopter flight instrument panels. AB - In this paper, we study the arrangement of displays in flight instrument panels of multi-purpose civil helicopters following a user-centered design method based on ergonomics principles. Our methodology can also be described as a user interface arrangement methodology based on user opinions and preferences. This study can be outlined as gathering user-centered data using two different research methods and then analyzing and integrating the collected data to come up with an optimal instrument panel design. An interview with helicopter pilots formed the first step of our research. In that interview, pilots were asked to provide a quantitative evaluation of basic interface arrangement principles. In the second phase of the research, a paper prototyping study was conducted with same pilots. The final phase of the study entailed synthesizing the findings from interviews and observational studies to formulate an optimal flight instrument arrangement methodology. The primary results that we present in our paper are the methodology that we developed and three new interface arrangement concepts, namely relationship of inseparability, integrated value and locational value. An optimum instrument panel arrangement is also proposed by the researchers. PMID- 26154209 TI - Digging deeper into the assessment of upper arm elevation angles using standard inclinometry. PMID- 26154210 TI - Global drivers, sustainable manufacturing and systems ergonomics. AB - This paper briefly explores the expected impact of the 'Global Drivers' (such as population demographics, food security; energy security; community security and safety), and the role of sustainability engineering in mitigating the potential effects of these Global Drivers. The message of the paper is that sustainability requires a significant input from Ergonomics/Human Factors, but the profession needs some expansion in its thinking in order to make this contribution. Creating a future sustainable world in which people experience an acceptable way of life will not happen without a large input from manufacturing industry into all the Global Drivers, both in delivering products that meet sustainability criteria (such as durability, reliability, minimised material requirement and low energy consumption), and in developing sustainable processes to deliver products for sustainability (such as minimum waste, minimum emissions and low energy consumption). Appropriate changes are already being implemented in manufacturing industry, including new business models, new jobs and new skills. Considerable high-level planning around the world is in progress and is bringing about these changes; for example, there is the US 'Advanced Manufacturing National Program' (AMNP)', the German 'Industrie 4.0' plan, the French plan 'la nouvelle France industrielle' and the UK Foresight publications on the 'Future of Manufacturing'. All of these activities recognise the central part that humans will continue to play in the new manufacturing paradigms; however, they do not discuss many of the issues that systems ergonomics professionals acknowledge. This paper discusses a number of these issues, highlighting the need for some new thinking and knowledge capture by systems ergonomics professionals. Among these are ethical issues, job content and skills issues. Towards the end, there is a summary of knowledge extensions considered necessary in order that systems ergonomists can be fully effective in this new environment, together with suggestions for the means to acquire and disseminate the knowledge extensions. PMID- 26154211 TI - Modeling people with motor disabilities to empower the automatic accessibility and ergonomic assessment of new products. AB - Virtual User Models (VUMs) can be a valuable tool for accessibility and ergonomic evaluation of designs in simulation environments. As increasing the accessibility of a design is usually translated into additional costs and increased development time, the need for specifying the percentage of population for which the design will be accessible is crucial. This paper addresses the development of VUMs representing specific groups of people with disabilities. In order to create such VUMs, we need to know the functional limitations, i.e. disability parameters, caused by each disability and their variability over the population. Measurements were obtained from 90 subjects with motor disabilities and were analyzed using both parametric and nonparametric regression methods as well as a proposed hybrid regression method able to handle small sample sizes. Validation results showed that in most cases the proposed regression analysis can produce valid estimations on the variability of each disability parameter. PMID- 26154212 TI - Seat and seatbelt accommodation in fire apparatus: Anthropometric aspects. AB - This study developed anthropometric information on U.S. firefighters to guide fire-apparatus seat and seatbelt designs and future standards development. A stratified sample of 863 male and 88 female firefighters across the U.S. participated in the study. The study results suggested 498 mm in width, 404 mm in depth, and 365-476 mm in height for seat pans; 429-522 mm in width and 542 mm in height for seat back; 871 mm in height for head support; a seat space of 733 mm at shoulder and 678 mm at hip; and a knee/leg clearance of 909 mm in fire truck cab. Also, 1520 mm of lap belt web effective length and 2828 mm of lap-and shoulder belt web effective length were suggested. These data for fire-truck seats and seatbelts provide a foundation for fire apparatus manufacturers and standards committees to improve firefighter seat designs and seatbelt usage compliance. PMID- 26154213 TI - Development of safety incident coding systems through improving coding reliability. AB - This paper reviews classification theory sources to develop five research questions concerning factors associated with incident coding system development and use and how these factors affect coding reliability. Firstly, a method was developed to enable the comparison of reliability results obtained using different methods. Second, a statistical and qualitative review of reliability studies was conducted to investigate the influence of the identified factors on the reliability of incident coding systems. As a result several factors were found to have a statistically significant effect on reliability. Four recommendations for system development and use are provided to assist researchers in improving the reliability of incident coding systems in high hazard industries. PMID- 26154214 TI - Job hindrances, job resources, and safety performance: The mediating role of job engagement. AB - Job engagement has received widespread attention in organizational research but has rarely been empirically investigated in the context of safety. In the present study, we examined the mediating role of job engagement in the relationships between job characteristics and safety performance using self-reported data collected at a coal mining company in China. Most of our study hypotheses were supported. Job engagement partially mediated the relationships between job resources and safety performance dimensions. Theoretical and practical implications and directions for future research are also discussed. PMID- 26154215 TI - Work demands and health consequences of organizational and technological measures introduced to enhance the quality of home care services--A subgroup analysis. AB - This study of home care workers in a Norwegian municipality aimed to examine the effect of two measures involving organizational (job checklists) and technological (personal digital assistants) job aids on perceived work demands and musculoskeletal health. Questionnaire data was collected in 2009 (n = 138, response rate 76.2%) and 2011 (n = 80, response rate 54%). Forty-six home care workers responded at both waves. Respondents were assigned into 'high', 'moderate' and 'low' strain groups based on their responses to open and closed survey questions regarding impact of the two measures. One-way ANOVA with post hoc t-tests and regression analyses investigated group differences and examined development in variables. Perceived work demands and health effects over the two year study period were unchanged overall, yet significant differences between subgroups were highlighted. Work demands and shoulder-neck pain remained high for high-strain workers, but were reduced for low and moderate strain workers. Management should be aware of diversity in worker responses to rationalizations and give priority to supplementary, targeted measures to counteract adverse effects. PMID- 26154216 TI - Association of individual and work-related risk factors with musculoskeletal symptoms among Iranian sewing machine operators. AB - This cross-sectional study evaluated working conditions and the occurrence of self-reported musculoskeletal symptoms among 251 Iranian sewing machine operators. A questionnaire and direct observations of working postures using the rapid upper limb assessment (RULA) method were used. A high prevalence of musculoskeletal symptoms, particularly in the neck/shoulders, back and hands/wrists were found. The mean RULA grand score of 5.7 highlighted a poor sewing workstation design and indicated that most operators (with posture assessed at action level 3) needed an investigation and changes in their working habits soon. Work-related factors (including number of years worked as an operator, prolonged working hours per shift, long duration of sitting work without a break, feeling pressure due to work and working postures) and individual factors (including age, gender, BMI and regular sport/physical activities) were associated with musculoskeletal symptoms in multiple logistic regression models. The findings add to the understanding of working conditions of those jobs involving sewing activities and emphasise the need for ergonomic interventions to reduce musculoskeletal symptoms in the future. PMID- 26154217 TI - Managing children's postural risk when using mobile technology at home: Challenges and strategies. AB - Maintaining the musculoskeletal health of children using mobile information and communication technologies (ICT) at home presents a challenge. The physical environment influences postures during ICT use and can contribute to musculoskeletal complaints. Few studies have assessed postures of children using ICT in home environments. The present study investigated the Rapid Upper Limb Assessment (RULA) scores determined by 16 novice and 16 experienced raters. Each rater viewed 11 videotaped scenarios of a child using two types of mobile ICT at home. The Grand Scores and Action Levels determined by study participants were compared to those of an ergonomist experienced in postural assessment. All postures assessed were rated with an Action Level of 2 or above; representing a postural risk that required further investigation and/or intervention. The sensitivity of RULA to assess some of the unconventional postures adopted by children in the home is questioned. PMID- 26154218 TI - The inter-rater reliability of Strain Index and OCRA Checklist task assessments in cheese processing. AB - The purpose of this study was to characterize the inter-rater reliability of two physical exposure assessment methods of the upper extremity, the Strain Index (SI) and Occupational Repetitive Actions (OCRA) Checklist. These methods are commonly used in occupational health studies and by occupational health practitioners. Seven raters used the SI and OCRA Checklist to assess task-level physical exposures to the upper extremity of workers performing 21 cheese manufacturing tasks. Inter-rater reliability was characterized using a single measure, agreement-based intraclass correlation coefficient (ICC). Inter-rater reliability of SI assessments was moderate to good (ICC = 0.59, 95% CI: 0.45 0.73), a similar finding to prior studies. Inter-rater reliability of OCRA Checklist assessments was excellent (ICC = 0.80, 95% CI: 0.70-0.89). Task complexity had a small, but non-significant, effect on inter-rater reliability SI and OCRA Checklist scores. Both the SI and OCRA Checklist assessments possess adequate inter-rater reliability for the purposes of occupational health research and practice. The OCRA Checklist inter-rater reliability scores were among the highest reported in the literature for semi-quantitative physical exposure assessment tools of the upper extremity. The OCRA Checklist however, required more training time and time to conduct the risk assessments compared to the SI. PMID- 26154219 TI - When is job rotation perceived useful and easy to use to prevent work-related musculoskeletal complaints? AB - Job rotation is often recommended to optimize physical work demands and prevent work-related musculoskeletal complaints, but little is known about possible facilitators and barriers to its usefulness and ease of use. Following a qualitative research design, semi-structured interviews with employers (n = 12) and workers (n = 11) from the construction industry were conducted. Organizational climate, job autonomy, job characteristics and work processes were mentioned as either facilitators or barriers on an organizational level. Worker characteristics, work behavior and attitude were mentioned as either facilitators or barriers on an individual level. Following a structured approach to assess usefulness of job rotation to optimize physical work exposures and identifying barriers to usefulness and ease of use in relevant stakeholder groups is necessary in order to select or develop strategies to overcome these barriers, or to reject job rotation as a useful or easy to use intervention in the given context. PMID- 26154220 TI - Objective classification of performance in the use of a piercing saw in jewellery making. AB - Data from 15 jewellery students, in their 1st and 3rd years of training, were analysed to show how data collected from work settings can be used to objectively evaluate performance in the use of tools. Participants were asked to use a piercing saw to cut 5 lines in a piece of metal. Performance was categorised in terms of functional dynamics. Data from strain gauges and a tri-axial accelerometer (built into the handle of the saw) were recorded and thirteen metrics derived from these data. The key question for this paper is which metrics could be used to distinguish levels of ability. Principal Components Analysis identified five components: sawing action; grasp of handle; task completion time; lateral deviation of strokes; and quality of lines cut. Using representative metrics for these components, participants could be ranked in terms of performance (low, medium, high) and statistical analysis showed significant differences between participants on key metrics. PMID- 26154221 TI - Anthropometric study of farm workers on Java Island, Indonesia, and its implications for the design of farm tools and equipment. AB - Anthropometric data are a prerequisite for designing agricultural tools and equipment that enable workers to achieve better performance and productivity while providing better safety and comfort. A set of thirty anthropometric dimensions was collected from a total sample of 371 male and female farm-workers from three different regions (west, central and east) of Java Island, Indonesia. The mean stature is 162.0 cm and 152.5 cm, the sitting height is 82.9 cm and 77.4 cm, and the body weight is 57.1 kg and 52.3 kg for male and female subjects, respectively. The index of relative sitting height (RSH) was 0.51 on average for both male and female subjects. Significant differences are found in most of the anthropometric dimensions between gender and regional data groups as well. Compared with groups of people from several other countries, the anthropometric dimensions of Indonesian people are quite similar to Indian people, but are relatively smaller than Filipino, Chinese, Japanese, British, and American people. An attempt was conducted to illustrate the use of this anthropometric database and ergonomic considerations in refining the design of traditional tools and equipment commonly in use for rice farming operations. PMID- 26154222 TI - A better way of fitting clips? A comparative study with respect to physical workload. AB - The clip fitting task is a frequently encountered assembly operation in the car industry. It can cause upper limb pain. During task laboratory simulations, upper limb muscular activity and external force were compared for 4 clip fitting methods: with the bare hand, with an unpowered tool commonly used at a company and with unpowered and powered prototype tools. None of the 4 fitting methods studied induced a lower overall workload than the other three. Muscle activity was lower at the dominant limb when using the unpowered tools and at the non dominant limb with the bare hand or with the powered tool. Fitting clips with the bare hand required a higher external force than fitting with the three tools. Evaluation of physical workload was different depending on whether external force or muscle activity results were considered. Measuring external force only, as recommended in several standards, is insufficient for evaluating physical workload. PMID- 26154223 TI - Interruptions in the wild: Development of a sociotechnical systems model of interruptions in the emergency department through a systematic review. AB - Interruptions are unavoidable in the "interrupt driven" Emergency Department (ED). A critical review and synthesis of the literature on interruptions in the ED can offer insight into the nature of interruptions in complex real-world environments. Fifteen empirical articles on interruptions in the ED were identified through database searches. Articles were reviewed, critiqued, and synthesized. There was little agreement and several gaps in conceptualizing sociotechnical system factors, process characteristics, and interruption outcomes. While multiple outcomes of interruptions were mentioned, few were measured, and the relationship between multiple outcomes was rarely assessed. Synthesizing the literature and drawing on ergonomic concepts, we present a sociotechnical model of interruptions in complex settings that motivates new directions in research and design. The model conceptualizes interruptions as a process, not a single event, that occurs within and is shaped by an interacting socio-technical system and that results in a variety of interrelated outcomes. PMID- 26154224 TI - Prevention of musculoskeletal disorders within management systems: A scoping review of practices, approaches, and techniques. AB - The purpose of this study was to identify and summarize the current research evidence on approaches to preventing musculoskeletal disorders (MSD) within Occupational Health and Safety Management Systems (OHSMS). Databases in business, engineering, and health and safety were searched and 718 potentially relevant publications were identified and examined for their relevance. Twenty-one papers met the selection criteria and were subjected to thematic analysis. There was very little literature describing the integration of MSD risk assessment and prevention into management systems. This lack of information may isolate MSD prevention, leading to difficulties in preventing these disorders at an organizational level. The findings of this review argue for further research to integrate MSD prevention into management systems and to evaluate the effectiveness of the approach. PMID- 26154225 TI - Virtual Sliding QWERTY: A new text entry method for smartwatches using Tap-N Drag. AB - A smaller screen of smartwatches compare to conventional mobile devices such as PDAs and smartphones is one of the main factors that makes users to input texts difficult. However, several studies have only proposed a concept for entering texts for smartwatches without usability tests while other studies showed low text input performance. In this study, we proposed a new text entry method called Virtual Sliding QWERTY (VSQ) which utilizes a virtual qwerty-layout keyboard and a 'Tap-N-Drag' method to move the keyboard to the desired position. In addition, to verify VSQ we conducted a usability test with 20 participants for a combination of 5 key sizes and 4 CD-gains. As a result, VSQ achieved an average of 11.9 Words per Minute which was higher than previous studies. In particular, VSQ at 5 * 5 key size and 2*, or 3* CD-gain had the highest performance in terms of the quantitative and qualitative usability test. PMID- 26154226 TI - Evaluating change in user error when using ruggedized handheld devices. AB - The increasing number of handheld mobile devices used today and the increasing dependency on them in the workplace makes understanding how users interact with these devices critical. This study seeks to understand how user error changes based on user age as well as input content type on ruggedized handheld devices. Participants completed data entry tasks of word and character input on two different devices, a physical keypad and touchscreen device. The number of errors and types of error, corrected and permanent were collected for each participant. Based on results on the study, touchscreen devices proved to be the optimal ruggedized handheld device to minimize user error. PMID- 26154227 TI - Schoolbag carriage and schoolbag-related musculoskeletal discomfort among primary school children. AB - Schoolbag carriage is a common occurrence and has been associated with musculoskeletal discomfort in children. The current study investigated the relationship between schoolbag-related musculoskeletal discomfort and individual, physical and psychosocial risk factors in primary school children in Ireland. A cross-sectional survey and pretest-posttest quasi-experimental design was used. The site and intensity of musculoskeletal discomfort was assessed before and after schoolbag carriage to provide a dose-response assessment of schoolbag related discomfort for the first time. Objective measurements of the children, schoolbags and other additional items were made, and a researcher assisted questionnaire was completed on arrival at school. A total of 529 children (male 55.8%: female 44.2%) with a mean age of 10.6 years +/- 7.14 months were included. The majority had backpacks (93.8%) and 89.7% (n = 445) carried the backpack over 2 shoulders. The mean schoolbag weight (4.8 +/- 1.47 kgs) represented a mean % body weight (%BW) of 12.6 +/- 4.29%. Only 29.9% carried schoolbags that were <=10%BW. A significantly greater proportion of normal weight children carried schoolbags that were >10%BW compared to overweight/obese children (p < 0.001). The mean %BW carried was 18.3 +/- 5.03 for those who had an additional item. The majority (77.5%) carried schoolbags to school for <=10 min. The prevalence of baseline musculoskeletal discomfort was high (63.4%). Schoolbag-related discomfort was reported more frequently in the shoulders (27.3%) than in the back (15%). The dose-response assessment indicated that both statistically and meaningfully significant increases in discomfort were observed following schoolbag carriage. Multiple logistic regression models indicated that psychosocial factors and a history of discomfort were predictors of schoolbag related back discomfort, while gender (being female) and a history of discomfort were predictors of schoolbag-related shoulder discomfort. None of the physical factors (absolute/relative schoolbag weight, carrying an additional item, duration of carriage, method of travel to school) were associated with schoolbag related discomfort. This study highlights the need to consider the multi factorial nature of schoolbag-related discomfort in children, and also the need to identify background pain as its presence can inadvertently influence the reporting of 'schoolbag-related' discomfort if it is not accounted for. PMID- 26154229 TI - Detailed assessment of low-back loads may not be worth the effort: A comparison of two methods for exposure-outcome assessment of low-back pain. AB - The trade-off between feasibility and accuracy of measurements of physical exposure at the workplace has often been discussed, but is unsufficiently understood. We therefore explored the effect of two low-back loading measurement tools with different accuracies on exposure estimates and their associations with low-back pain (LBP). Low-back moments of 93 workers were obtained using two methods: a moderately accurate observation-based method and a relatively more accurate video-analysis method. Group-based exposure metrics were assigned to a total of 1131 workers who reported on their LBP status during three follow-up years. The two methods were compared regarding individual and group-based moments and their predictive value for LBP. Differences between the two methods for peak moments were high at the individual level and remained substantial at group level. For cumulative moments, differences between the two methods were attenuated as random inaccuracies cancelled out. Peak moments were not predictive for LBP in any method while cumulative moments were, suggesting comparable predictive values of the two methods. While assessment of low-back load improves from investing in collecting relatively more accurate individual-based data, this does not necessarily lead to better predictive values on a group level, especially not for cumulative loads. PMID- 26154228 TI - A systematic review of mixed methods research on human factors and ergonomics in health care. AB - This systematic literature review provides information on the use of mixed methods research in human factors and ergonomics (HFE) research in health care. Using the PRISMA methodology, we searched four databases (PubMed, PsycInfo, Web of Science, and Engineering Village) for studies that met the following inclusion criteria: (1) field study in health care, (2) mixing of qualitative and quantitative data, (3) HFE issues, and (4) empirical evidence. Using an iterative and collaborative process supported by a structured data collection form, the six authors identified a total of 58 studies that primarily address HFE issues in health information technology (e.g., usability) and in the work of healthcare workers. About two-thirds of the mixed methods studies used the convergent parallel study design where quantitative and qualitative data were collected simultaneously. A variety of methods were used for collecting data, including interview, survey and observation. The most frequent combination involved interview for qualitative data and survey for quantitative data. The use of mixed methods in healthcare HFE research has increased over time. However, increasing attention should be paid to the formal literature on mixed methods research to enhance the depth and breadth of this research. PMID- 26154230 TI - Participatory ergonomics simulation of hospital work systems: The influence of simulation media on simulation outcome. AB - Current application of work system simulation in participatory ergonomics (PE) design includes a variety of different simulation media. However, the actual influence of the media attributes on the simulation outcome has received less attention. This study investigates two simulation media: full-scale mock-ups and table-top models. The aim is to compare, how the media attributes of fidelity and affordance influence the ergonomics identification and evaluation in PE design of hospital work systems. The results illustrate, how the full-scale mock-ups' high fidelity of room layout and affordance of tool operation support ergonomics identification and evaluation related to the work system entities space and technologies & tools. The table-top models' high fidelity of function relations and affordance of a helicopter view support ergonomics identification and evaluation related to the entity organization. Furthermore, the study addresses the form of the identified and evaluated conditions, being either identified challenges or tangible design criteria. PMID- 26154231 TI - Overload depending on driving experience and situation complexity: Which strategies faced with a pedestrian crossing? AB - The purpose of this study was to identify the influence of situation complexity and driving experience on subjective workload and driving performance, and the less costly and the most effective strategies faced with a hazard pedestrian crossing. Four groups of young drivers (15 traditionally trained novices, 12 early-trained novices, 15 with three years of experience and 15 with a minimum of five years of experience) were randomly assigned to three situations (simple, moderately complex and very complex) including unexpected pedestrian crossings, in a driving simulator. The subjective workload was collected by the NASA-TLX questionnaire after each situation. The main results confirmed that the situation complexity and the lack of experience increased the subjective workload. Moreover, the subjective workload, the avoidance strategies and the reaction times influenced the number of collisions depending on situation complexity and driving experience. These results must be taken into account to target the prevention actions. PMID- 26154232 TI - A comparison of linear and logarithmic auditory tones in pulse oximeters. AB - This study compared the ability of forty anaesthetists to judge absolute levels of oxygen saturation, direction of change, and size of change in saturation using auditory pitch and pitch difference in two laboratory-based studies that compared a linear pitch scale with a logarithmic scale. In the former the differences in saturation become perceptually closer as the oxygenation level becomes higher whereas in the latter the pitch differences are perceptually equivalent across the whole range of values. The results show that anaesthetist participants produce significantly more accurate judgements of both absolute oxygenation values and size of oxygenation level difference when a logarithmic, rather than a linear, scale is used. The line of best fit for the logarithmic function was also closer to x = y than for the linear function. The results of these studies can inform the development and standardisation of pulse oximetry tones in order to improve patient safety. PMID- 26154233 TI - Body size and ability to pass through a restricted space: Observations from 3D scanning of 210 male UK offshore workers. AB - Offshore workers are subjected to a unique physical and cultural environment which has the ability to affect their size and shape. Because they are heavier than the UK adult population we hypothesized they would have larger torso dimensions which would adversely affect their ability to pass one another in a restricted space. A sample of 210 male offshore workers was selected across the full weight range, and measured using 3D body scanning for shape. Bideltoid breadth and maximum chest depth were extracted from the scans and compared with reference population data. In addition a size algorithm previously calculated on 44 individuals was applied to adjust for wearing a survival suit and re-breather device. Mean bideltoid breadth and chest depth was 51.4 cm and 27.9 cm in the offshore workers, compared with 49.7 cm and 25.4 cm respectively in the UK population as a whole. Considering the probability of two randomly selected people passing within a restricted space of 100 cm and 80 cm, offshore workers are 28% and 34% less likely to pass face to face and face to side respectively, as compared with UK adults, an effect which is exacerbated when wearing personal protective equipment. PMID- 26154234 TI - A coupling system to predict the core and skin temperatures of human wearing protective clothing in hot environments. AB - The aim of this study is to predict the core and skin temperatures of human wearing protective clothing in hot environments using the coupling system. The coupling system consisted of a sweating manikin Newton controlled by a multi-node human thermal model, and responded dynamically to the thermal environment as human body. Validation of the coupling system results was conducted by comparison with the subject tests. Five healthy men wearing protective clothing were exposed to the thermal neutral and high temperature environments. The skin temperatures of seven body segments and the rectal temperatures were recorded continuously. The predictions of core temperatures made by the coupling system showed good agreement with the experimental data, with maximum difference of 0.19 degrees C and RMSD of 0.12 degrees C. The predicted mean skin temperatures fell outside of the 95% CI for most points, whereas the difference between the simulated results and measured data was no more than 1 degrees C which is acceptable. The coupling system predicted the local skin temperatures reasonably with the maximum local skin temperature of 1.30 degrees C. The coupling system has been validated and exhibited reasonable accuracy compared with the experimental results. PMID- 26154235 TI - The implementation of ergonomics advice and the stage of change approach. AB - This paper investigates the implementation of injury prevention advice tailored according to the Stage of Change (SOC) approach. The managers of 25 workgroups, drawn from medium to large companies across a wide range of occupational sectors were allocated to receive either standard ergonomics advice or ergonomics advice tailored according to the workgroup SOC. Twelve months after the advice was provided, semi-structured interviews were conducted with each manager. In a multivariate model, managers who had received tailored advice were found to have implemented significantly more of the recommended changes (IRR = 1.68, 95% CI 1.07-2.63) and more "additional" changes (IRR = 1.90, 95% CI 1.12-3.20). Qualitative analysis identified that the key barriers and facilitators to the implementation of changes were largely related to worker resistance to change and the attitudes of senior managers towards health and safety. The findings from this study suggest that the implementation of ergonomics recommendations may be improved by the tailoring of advice according to SOC principles. PMID- 26154236 TI - Pre-flight safety briefings, mood and information retention. AB - Mood is a moderating factor that is known to affect performance. For airlines, the delivery of the pre-flight safety briefing prior to a commercial flight is not only an opportunity to inform passengers about the safety features on-board the aircraft they are flying, but an opportunity to positively influence their mood, and hence performance in the unlikely event of an emergency. The present research examined whether indeed the pre-flight safety briefing could be used to positively impact passengers' mood. In addition, the present research examined whether the recall of key safety messages contained within the pre-flight safety briefing was influenced by the style of briefing. Eighty-two participants were recruited for the research and divided into three groups; each group exposed to a different pre-flight cabin safety briefing video (standard, humorous, movie theme). Mood was measured prior and post safety briefing. The results revealed that pre-flight safety briefing videos can be used to manipulate passengers' mood. Safety briefings that are humorous or use movie themes to model their briefing were found to positively affect mood. However, there was a trade-off between entertainment and education, the greater the entertainment value, the poorer the retention of key safety messages. The results of the research are discussed from both an applied and theoretical perspective. PMID- 26154237 TI - Effects of two ergonomic improvements in brazing coils of air-handler units. AB - The research aims to address the physically loading task and quality and productivity problems in the brazing of coils of air-handler units. Eight operators participated in two intervention studies conducted in a factory in Malaysia to compare the status quo brazing with (1) the use of a new twin-brazing torch that replaced the single-brazing gun and (2) brazing in a sitting position. The outcome measures are related to quality, productivity, monetary costs, body postures and symptoms. After baseline, Interventions I and II were applied for 3 months respectively. The results show a 58.9% quality improvement, 140% productivity increase and 113 times ROI. There was also a reduction in poor work postures e.g. in the raising of the arms and shoulders; bending, twisting and extending of the neck; and bending of left and right wrists, and the back. This research can be replicated in other factories that share similar processes. PMID- 26154238 TI - Understanding subtle changes in medium-range order in amorphous silicon. AB - Based on a detailed study of the radial distribution function (RDF) of a model for amorphous silicon (a-Si), we address the relation between short-range rearrangements and an increase in medium-range order induced by thermal relaxation. Recent experimental measurements have shown that a small peak appears in the RDF around 4.7 A upon annealing, along with other subtle changes, and this is attributed to ordering among the dihedral angles. We show that, although this is a possible explanation, an increase in short-range order (up to second neighbors) is not only necessary for these changes to occur, but could also be their sole cause. To clarify the nature of disorder in the amorphous system, correlations among dihedral and tetrahedral angles are examined. The bivariate probability distribution of these two variables reveals small correlations between dihedral and tetrahedral angles, associated with the staggered and eclipsed conformations. In the first case, bond angles around 112.5[Formula: see text] are favored versus 120[Formula: see text] in the second case. Bond angles between 95[Formula: see text] and 100[Formula: see text] are less probable in both conformations. PMID- 26154239 TI - Veterinary Medicine and Multi-Omics Research for Future Nutrition Targets: Metabolomics and Transcriptomics of the Common Degenerative Mitral Valve Disease in Dogs. AB - Canine degenerative mitral valve disease (DMVD) is the most common form of heart disease in dogs. The objective of this study was to identify cellular and metabolic pathways that play a role in DMVD by performing metabolomics and transcriptomics analyses on serum and tissue (mitral valve and left ventricle) samples previously collected from dogs with DMVD or healthy hearts. Gas or liquid chromatography followed by mass spectrophotometry were used to identify metabolites in serum. Transcriptomics analysis of tissue samples was completed using RNA-seq, and selected targets were confirmed by RT-qPCR. Random Forest analysis was used to classify the metabolites that best predicted the presence of DMVD. Results identified 41 known and 13 unknown serum metabolites that were significantly different between healthy and DMVD dogs, representing alterations in fat and glucose energy metabolism, oxidative stress, and other pathways. The three metabolites with the greatest single effect in the Random Forest analysis were gamma-glutamylmethionine, oxidized glutathione, and asymmetric dimethylarginine. Transcriptomics analysis identified 812 differentially expressed transcripts in left ventricle samples and 263 in mitral valve samples, representing changes in energy metabolism, antioxidant function, nitric oxide signaling, and extracellular matrix homeostasis pathways. Many of the identified alterations may benefit from nutritional or medical management. Our study provides evidence of the growing importance of integrative approaches in multi omics research in veterinary and nutritional sciences. PMID- 26154240 TI - Benzoic acid derivatives with improved antifungal activity: Design, synthesis, structure-activity relationship (SAR) and CYP53 docking studies. AB - Previously, we identified CYP53 as a fungal-specific target of natural phenolic antifungal compounds and discovered several inhibitors with antifungal properties. In this study, we performed similarity-based virtual screening and synthesis to obtain benzoic acid-derived compounds and assessed their antifungal activity against Cochliobolus lunatus, Aspergillus niger and Pleurotus ostreatus. In addition, we generated structural models of CYP53 enzyme and used them in docking trials with 40 selected compounds. Finally, we explored CYP53-ligand interactions and identified structural elements conferring increased antifungal activity to facilitate the development of potential new antifungal agents that specifically target CYP53 enzymes of animal and plant pathogenic fungi. PMID- 26154241 TI - Strong positive cooperativity in binding to the A3T3 repeat by Hoechst 33258 derivatives attaching the quinoline units at the end of a branched linker. AB - Hoechst 33258 derivatives with additional interacting moieties attached at the ends of branched linkers were synthesized, and their DNA binding properties were investigated with regard to the A3T3 repeat by measuring fluorescence spectra. The binding property of the ligand was investigated by fluorescence titration, and the titration data were analyzed using the McGhee-von Hippel method. Ligand 6Q with the quinolin-6-yloxyacetyl group and Ligand IQ with isoquinolin-6 yloxyacetyl group at the ends of the branched linkers exhibit highly positive cooperativity for the DNA having 5 A3T3 sites with 3 base-insertions between them with sequence selectivity. The strategy developed in this study may be generally applicable for designing ligands for repetitive DNA sequences. PMID- 26154242 TI - Stigmatizing attitudes toward mental illness among primary school children in Kenya. AB - BACKGROUND: Literature describing stigmatizing attitudes towards people with mental illness by children in the developing world is lacking. Children's mental health issues in the Kenyan context are especially pertinent due to the increased likelihood of exposure to risk factors and the high prevalence of mental disorders. The objective of the current study was to examine socio-demographic factors associated with the endorsement of stigmatizing attitudes towards people with mental illness among Kenyan school children. METHODS: We analyzed cross sectional survey data from 4585 primary school-aged children in standards one through seven in the Eastern Province of Kenya. We examined relationships between the endorsement of stigmatizing attitudes and age, gender, district, religion, being in the standard appropriate for one's age, and parental employment status. RESULTS: Stigma scores decreased with increasing age (beta = -0.83; 95 % CI = 0.99 to -0.67). Boys had higher stigma scores compared to girls (beta = 1.55; 95 % CI = 0.86-2.24). Students from the rural district had higher average stigma scores as compared to those from the peri-urban district (beta = 1.14; 95 % CI = 0.44-1.84). Students who were not in the standard appropriate for their age had lower stigma scores than those who were in the standard typical for their age (beta = -1.60; 95 % CI = -2.43 to -0.77). CONCLUSIONS: Stigmatizing attitudes toward the mentally ill exist among primary school children in Kenya; thus, anti stigma interventions are needed, and our findings highlight particular subgroups that could be targeted. PMID- 26154243 TI - Basic fibroblast growth factor is pro-adipogenic in rat skeletal muscle progenitor clone, 2G11 cells. AB - Intramuscular adipose tissue (IMAT) formation is a hallmark of marbling in cattle. IMAT is considered to originate from skeletal muscle progenitor cells with adipogenic potential. However, the mechanism involved in IMAT formation from these progenitor cells in vivo remains unclear. In the present study, among the growth factors tested, which were known to be expressed in skeletal muscle, we found only basic fibroblast growth factor (bFGF) has a pro-adipogenic effect on skeletal muscle derived adipogenic progenitor clone, 2G11 cells. Pre-exposure of 2G11 cells to bFGF did not affect initial gene expressions of CCAAT/enhancer binding protein (C/EBP)beta and C/EBPdelta, while resulting in an enhancement of subsequent expressions of C/EBPalpha and proliferator-activated receptor gamma (PPARgamma) during adipogenesis, indicating that bFGF is acting on the transcriptional regulation of C/EBPalpha and PPARgamma. In addition, the effect of bFGF is mediated via two types of FGF receptor (FGFR) isoforms: FGFR1 and FGFR2 IIIc, and both receptors are prerequisite for bFGF to express its pro adipogenic effect. These results suggest that bFGF plays an important role as a key trigger of IMAT formation in vivo. PMID- 26154246 TI - Fabrication of Elemental Copper by Intense Pulsed Light Processing of a Copper Nitrate Hydroxide Ink. AB - Printed electronics and renewable energy technologies have shown a growing demand for scalable copper and copper precursor inks. An alternative copper precursor ink of copper nitrate hydroxide, Cu2(OH)3NO3, was aqueously synthesized under ambient conditions with copper nitrate and potassium hydroxide reagents. Films were deposited by screen-printing and subsequently processed with intense pulsed light. The Cu2(OH)3NO3 quickly transformed in less than 100 s using 40 (2 ms, 12.8 J cm(-2)) pulses into CuO. At higher energy densities, the sintering improved the bulk film quality. The direct formation of Cu from the Cu2(OH)3NO3 requires a reducing agent; therefore, fructose and glucose were added to the inks. Rather than oxidizing, the thermal decomposition of the sugars led to a reducing environment and direct conversion of the films into elemental copper. The chemical and physical transformations were studied with XRD, SEM, FTIR and UV vis. PMID- 26154247 TI - Transoral mandibulectomy and double barrel fibular flap reconstruction. PMID- 26154248 TI - Expedient Access to 2,3-Dihydropyridines from Unsaturated Oximes by Rh(III) Catalyzed C-H Activation. AB - alpha,beta-Unsaturated oxime pivalates are proposed to undergo reversible C(sp(2))-H insertion with cationic Rh(III) complexes to furnish five-membered metallacycles. In the presence of 1,1-disubstituted olefins, these species participate in irreversible migratory insertion to give, after reductive elimination, 2,3-dihydropyridine products in good yields. Catalytic hydrogenation can then be used to convert these molecules into piperidines, which are important structural components of numerous pharmaceuticals. PMID- 26154249 TI - An Equivalence Trial Comparing Instructor-Regulated With Directed Self-Regulated Mastery Learning of Advanced Cardiac Life Support Skills. AB - INTRODUCTION: Instructor-led simulation-based mastery learning of advanced cardiac life support (ACLS) skills is an effective and focused approach to competency-based education. Directed self-regulated learning (DSRL) may be an effective and less resource-intensive way to teach ACLS skills. METHODS: Forty first-year internal medicine residents were randomized to either simulation-based DSRL or simulation-based instructor-regulated learning (IRL) of ACLS skills using a mastery learning model. Residents in each intervention completed pretest, posttest, and retention test of their performance in leading an ACLS response to a simulated scenario. Performance tests were assessed using a standardized checklist. Residents in the DSRL intervention were provided assessment instruments, a debriefing guide, and scenario-specific teaching points, and they were permitted to access relevant online resources. Residents in the IRL intervention had access to the same materials; however, the teaching and debriefing were instructor led. RESULTS: Skills of both the IRL and DSRL interventions showed significant improvement after the intervention, with an average improvement on the posttest of 21.7%. After controlling for pretest score, there was no difference between intervention arms on the posttest [F(1,37) = 0.02, P = 0.94] and retention tests [F(1,17) = 1.43, P = 0.25]. Cost savings were realized in the DSRL intervention after the fourth group (16 residents) had completed each intervention, with an ongoing savings of $80 per resident. CONCLUSIONS: Using a simulation-based mastery learning model, we observed equivalence in learning of ACLS skills for the DSRL and IRL conditions, whereas DSRL was more cost effective. PMID- 26154250 TI - Simulation Improves Procedural Protocol Adherence During Central Venous Catheter Placement: A Randomized Controlled Trial. AB - BACKGROUND: Simulation training may improve proficiency at and reduce complications from central venous catheter (CVC) placement, but the scope of simulation's effect remains unclear. This randomized controlled trial evaluated the effects of a pragmatic CVC simulation program on procedural protocol adherence, technical skill, and patient outcomes. METHODS: Internal medicine interns were randomized to standard training for CVC insertion or standard training plus simulation-based mastery training. Standard training involved a lecture, a video-based online module, and instruction by the supervising physician during actual CVC insertions. Intervention-group subjects additionally underwent supervised training on a venous access simulator until they demonstrated procedural competence. Raters evaluated interns' performance during internal jugular CVC placement on actual patients in the medical intensive care unit. Generalized estimating equations were used to account for outcome clustering within trainees. RESULTS: We observed 52 interns placing 87 CVCs. Simulation-trained interns exhibited better adherence to prescribed procedural technique than interns who received only standard training (P = 0.024). There were no significant differences detected in first-attempt or overall cannulation success rates, mean needle passes, global assessment scores, or complication rates. CONCLUSIONS: Simulation training added to standard training improved protocol adherence during CVC insertion by novice practitioners. This study may have been too small to detect meaningful differences in venous cannulation proficiency and other clinical outcomes, highlighting the difficulty of patient centered simulation research in settings where poor outcomes are rare. For high performing systems, where protocol deviations may provide an important proxy for rare procedural complications, simulation may improve CVC insertion quality and safety. PMID- 26154251 TI - Cognitive Load Theory for the Design of Medical Simulations. AB - STATEMENT: Simulation-based education (SBE) has emerged as an effective and important tool for medical educators, but research about how to optimize training with simulators is in its infancy. It is often difficult to generalize results from experiments on instructional design issues in simulation because of the heterogeneity of learner groups, teaching methods, and rapidly changing technologies. We have found that cognitive load theory is highly relevant to teaching in the simulation laboratory and a useful conceptual framework to reference when designing or researching simulation-based education. Herein, we briefly describe cognitive load theory, its grounding in our current understanding of cognitive architecture, and the evidence supporting it. We focus our discussion on a few well-established cognitive load effects with examples from simulation training and recommend some instructional applications with theoretical potential to improve learning outcomes. PMID- 26154252 TI - In response to a novel role for otolaryngologists in the multidisciplinary difficult airway response team. PMID- 26154253 TI - Neurofunctional Signature of Hyperfamiliarity for Unknown Faces. AB - Hyperfamiliarity for unknown faces is a rare selective disorder that consists of the disturbing and abnormal feeling of familiarity for unknown faces, while recognition of known faces is normal. In one such patient we investigated with a multimodal neuroimaging design the hitherto undescribed neural signature associated with hyperfamiliarity feelings. Behaviorally, signal detection methods revealed that the patient's discrimination sensitivity between familiar and unfamiliar faces was significantly lower than that of matched controls, and her response criterion for familiarity decisions was significantly more liberal. At the neural level, while morphometric analysis and single-photon emission CT (SPECT) showed the atrophy and hypofunctioning of the left temporal regions, functional magnetic resonance imaging (fMRI) revealed that hyperfamiliarity feelings were selectively associated to enhanced activity in the right medial and inferior temporal cortices. We therefore characterize the neurofunctional signature of hyperfamiliarity for unknown faces as related to the loss of coordinated activity between the complementary face processing functions of the left and right temporal lobes. PMID- 26154254 TI - Cardiovascular Health Score and the Risk of Cardiovascular Diseases. AB - In 2010 the American Heart Association proposed a definition of ideal health behaviors and health factors to measure cardiovascular health, from which Huffman et al. created the Cardiovascular Health Score (CVH score) to estimate these metrics on an individual level. We performed a prospective cohort study among employees of the Kailuan Group Corporation, who underwent a physical examination in 2006-2007 to investigate the relationship between the CVH score and the risk of cardiovascular disease (CVD). A total of 91,598 individuals free of stroke and myocardial infarction at baseline were included in the final analysis. We calculated baseline CVH score for each metric (poor=0, intermediate=1, ideal=2 points; range=0-14 points for all seven metrics) and categorized them into three groups: inadequate (0-4 points), average (5-9 points), and optimum (10-14 points). Incidence of total number of CVD events, myocardial infarction, and stroke was analyzed among these three groups and each incremental point on the CVH score. During an average 6.81 years of follow-up, there were 3276 CVD events, 2579 strokes and 747 myocardial infarction occurred. After adjusting for several confounding factors, each better health category of the CVH score was associated with reduced odds of 47% for all CVD events, and each point higher on the CVH score was associated with reduced odds of 18%. Similar trends were detected in the risks for myocardial infarction and stroke. A higher CVH score is therefore a protective factor for CVD, myocardial infarction, and stroke. PMID- 26154256 TI - [Hygiene and Infection Prevention in Medical Institutions, Kindergartens and Schools - Statutory Basis, Infection Control Practice and Experiences of the Public Health Services]. AB - Infection prevention is one of the main tasks of the public health services. The "Protection against infection act" places all medical institutions and facilities for children (kindergartens and schools) under the obligation to assume responsibility and to cooperate. Duties of the institutions are described, and public health services are obliged to perform hygiene control visits.Regarding medical institutions, the guidelines of the German Commission on Hospital Hygiene and Infection Control have to be observed, and the counties were obliged to publish hygiene enactments. Subsequently, good improvements in hygiene management in medical institutions were achieved. In schools, however, severe hygienic problems (i.e. sanitary hygiene, indoor air hygiene) are detected, without any improvement - obviously due to a missing sense of responsibility in the school community. Causes for poor behaviour prevention (hand hygiene, ventilation) and missing situational prevention (i.e. cleaning) are discussed. Without reversion to the obviously needed but nearly forgotten subject school hygiene, obligatory guidelines and the assuming of responsibility, permanent improvements cannot be achieved. PMID- 26154255 TI - Geraniol Suppresses Angiogenesis by Downregulating Vascular Endothelial Growth Factor (VEGF)/VEGFR-2 Signaling. AB - Geraniol exerts several direct pharmacological effects on tumor cells and, thus, has been suggested as a promising anti-cancer compound. Because vascularization is a major precondition for tumor growth, we analyzed in this study the anti angiogenic action of geraniol. In vitro, geraniol reduced the migratory activity of endothelial-like eEND2 cells. Western blot analyses further revealed that geraniol downregulates proliferating cell nuclear antigen (PCNA) and upregulates cleaved caspase-3 (Casp-3) expression in eEND2 cells. Moreover, geraniol blocked vascular endothelial growth factor (VEGF)/VEGFR-2 signal transduction, resulting in a suppression of downstream AKT and ERK signaling pathways. In addition, geraniol significantly reduced vascular sprout formation in a rat aortic ring assay. In vivo, geraniol inhibited the vascularization of CT26 tumors in dorsal skinfold chambers of BALB/c mice, which was associated with a smaller tumor size when compared to vehicle-treated controls. Immunohistochemical analyses confirmed a decreased number of Ki67-positive cells and CD31-positive microvessels with reduced VEGFR-2 expression within geraniol-treated tumors. Taken together, these findings indicate that geraniol targets multiple angiogenic mechanisms and, therefore, is an attractive candidate for the anti-angiogenic treatment of tumors. PMID- 26154257 TI - [Can Psychometric Tests Predict Success in the Selection Interview for Medical School? A Cross-Sectional Study at One German Medical School]. AB - Background The final exam grade is the main selection criterion for medical school application in Germany. For academic success, it seems to be a reliable predictor. Its use as the only selection criterion is, however, criticised. At some universities, personal interviews are part of the selection process. However, these are very time consuming and are of doubtful validity. The (additional) use of appropriate psychometric instruments could reduce the cost and increase the validity. This study investigates the extent to which psychometric instruments can predict the outcome of a personal selection interview. Methods This is a cross-sectional study on the correlation of the results of psychometric instruments with those of the personal selection interview as part of the application process. As the outcome, the score of the selection interview was used. The NEO - Five Factor Inventory, the Hospital Anxiety and Depression Scale (HADS) and the questionnaire to identify work related behaviour and experience patterns (AVEM) were used as psychometric interviews. Results There was a statistically significant correlation with the results of the personal selection interview for the sum score of the depression scale from the HADS and the sum score for the dimension of life satisfaction of the AVEM. In addition, those participants who did not previously complete an application training achieved a better result in the selection interview. Conclusion The instruments used measure different aspects than the interviews and cannot replace them. It remains to be seen whether the selected parameters are able to predict academic success. PMID- 26154258 TI - [Who Hits the Mark? A Comparative Study of the Free Geocoding Services of Google and OpenStreetMap]. AB - BACKGROUND: Geocoding, the process of converting textual information (addresses) into geographic coordinates is increasingly used in public health/epidemiological research and practice. To date, little attention has been paid to geocoding quality and its impact on different types of spatially-related health studies. The primary aim of this study was to compare 2 freely available geocoding services (Google and OpenStreetMap) with regard to matching rate (percentage of address records capable of being geocoded) and positional accuracy (distance between geocodes and the ground truth locations). METHODS: Residential addresses were geocoded by the NRW state office for information and technology and were considered as reference data (gold standard). The gold standard included the coordinates, the quality of the addresses (4 categories), and a binary urbanity indicator based on the CORINE land cover data. 2 500 addresses were randomly sampled after stratification for address quality and urbanity indicator (approximately 20 000 addresses). These address samples were geocoded using the geocoding services from Google and OSM. RESULTS: In general, both geocoding services showed a decrease in the matching rate with decreasing address quality and urbanity. Google showed consistently a higher completeness than OSM (>93 vs. >82%). Also, the cartographic confounding between urban and rural regions was less distinct with Google's geocoding API. Regarding the positional accuracy of the geo-coordinates, Google also showed the smallest deviations from the reference coordinates, with a median of <9 vs. <175.8 m. The cumulative density function derived from the positional accuracy showed for Google that nearly 95% and for OSM 50% of the addresses were geocoded within <50 m of their reference coordinates. CONCLUSION: The geocoding API from Google is superior to OSM regarding completeness and positional accuracy of the geocoded addresses. On the other hand, Google has several restrictions, such as the limitation of the requests to 2 500 addresses per 24 h and the presentation of the results exclusively on Google Maps, which may complicate the use for scientific purposes. PMID- 26154259 TI - [Amendments to the Drinking Water Ordinance: Legionellae in Hot Water Systems - Data from the Public Health Authority Frankfurt am Main, Germany]. AB - BACKGROUND: The first and second amendment to the Drinking Water Ordinance came in to force in the years 2011 and 2012 causing additional tasks and responsibilities for operators of commercial large-scale systems, usually hot water systems in large residential buildings, and for the local health authorities. This article describes the experiences of the health authority in Frankfurt/Main with these new regulations. Some of the revisions in the first amendment of the ordinance (TrinkwV 2001 (2011)) were omitted in the second revision (TrinkwV 2001 (2012)) such as the obligation to notify for large-scale systems. Furthermore, the intervals between the obligatory inspections were extended from 1 to 3 years and merely exceedances of the legal limits were to be notified in contrast to the previous obligation to notify all values. RESULTS: On the basis of the TrinkwV 2001 (2011) a large additional staff requirement had been estimated (13/21 positions). After the TrinkwV 2001 (2012) the tasks can be accomplished by less than 2 employees. While the notification obligation was still in force, the health authority received 4,461 notifications of large-scale systems, since then a further 477 have been notified. Of a total of 1,335 initial analyses, 794 (60%) exceeded the technical action value and in 113 properties with values exceeding 10,000/100 ml a usage restriction was necessary. CONCLUSIONS: Due to the suspension of the notification obligation to report any result of the analyses performed the assessment of the reports on large-scale systems has become difficult. An appropriate assessment of the implementation of the regulation is not possible, since the total number of large-scale systems is not known and a failure to report may result from a measured value below the technical action value as well as from a not inspected system. The large number of usage restrictions is an indication for the necessity to inspect and if required to treat and restore the system. PMID- 26154260 TI - [Design of a Curriculum Clinical Social Medicine]. AB - The economic transformation of health care systems, which is supported by both the economic and the political sector, is in demand of constant humane correction. Legal regulations of social systems securing health corresponding to the code of social law are guard rails for a responsible use of limited resources and are subject to constant development. All doctors caring for patients should be in a position to reflect the real life context of their patients as both causal and modifying influence for health and disease from a social medical perspective, apart from their specific medical field of expertise.Accordingly 3 parts of sub-specialization training are suggested: clinical tasks of social medicine as detailed in the code of social law, clinical social medicine in health care according to the 5(th) book of the code of social law and social medicine in clinical social medicine/participation. Higher level-of-care hospitals, as well as rehabilitation clinics, should offer sub-specialization in social medicine without interruption of employment contracts. Corresponding criteria for the regulation on further education should be formulated by the German Society of Social Medicine and Prevention (DGSMP) as the competent scientific association and presented to the committee on further education of the Federal Medical Association. This aims at strengthening social medicine in clinical care. PMID- 26154261 TI - Classification of alcohol use disorders among nightclub patrons: associations between high-risk groups, sociodemographic factors and illicit drug use. AB - BACKGROUND: Nightclubs are favorable environments for alcohol abuse and the use of other drugs among patrons. OBJECTIVE: To identify patterns of alcohol use in a high-risk population and their relationship with sociodemographic factors and illicit drug use. METHODS: A portal survey technique was used to recruit patrons in 31 nightclubs in the city of Sao Paulo, Brazil. A two stage sampling method allowed the selection of nightclubs and patrons within a nightclub. A total of 1057 patrons answered to a three stages-survey (nightclub entrance and exit face to-face interviews and a day-after online questionnaire). Entrance survey offered information on sociodemographic data and history of drug use. The day-after survey used the Alcohol Use Disorders Identifications Test (AUDIT) that identified patterns of alcohol abuse disorders. Data were modeled using an ordered logit regression analysis, considering sample weights. RESULTS: Almost half of the nightclub patrons presented any alcohol use disorder (AUDIT score >=8). Being male (OR = 1.68; 95% CI = 1.09-2.60) and single (OR = 1.71; 95% CI = 1.05-2.76) increased the chances for more severe alcohol use disorders. Having a graduate degree (OR = 0.57; 95% CI = 0.38-0.87) and age >=35 years (OR = 0.48; 95% CI = 0.27-0.85) decreased the chances of patrons' alcohol use disorders. The prevalence rates of past-year marijuana, cocaine and inhalants use increased with the increased level of alcohol use disorders. CONCLUSIONS: Patrons of nightclubs show higher prevalence rates for any alcohol use disorders than the general population. Patrons could benefit from governmental brief intervention or referral to treatment for alcohol used disorders disclosed in nightclubs. PMID- 26154262 TI - Mathematical Modeling of the Dynamics of Shoot-Root Interactions and Resource Partitioning in Plant Growth. AB - Plants are highly plastic in their potential to adapt to changing environmental conditions. For example, they can selectively promote the relative growth of the root and the shoot in response to limiting supply of mineral nutrients and light, respectively, a phenomenon that is referred to as balanced growth or functional equilibrium. To gain insight into the regulatory network that controls this phenomenon, we took a systems biology approach that combines experimental work with mathematical modeling. We developed a mathematical model representing the activities of the root (nutrient and water uptake) and the shoot (photosynthesis), and their interactions through the exchange of the substrates sugar and phosphate (Pi). The model has been calibrated and validated with two independent experimental data sets obtained with Petunia hybrida. It involves a realistic environment with a day-and-night cycle, which necessitated the introduction of a transitory carbohydrate storage pool and an endogenous clock for coordination of metabolism with the environment. Our main goal was to grasp the dynamic adaptation of shoot:root ratio as a result of changes in light and Pi supply. The results of our study are in agreement with balanced growth hypothesis, suggesting that plants maintain a functional equilibrium between shoot and root activity based on differential growth of these two compartments. Furthermore, our results indicate that resource partitioning can be understood as the emergent property of many local physiological processes in the shoot and the root without explicit partitioning functions. Based on its encouraging predictive power, the model will be further developed as a tool to analyze resource partitioning in shoot and root crops. PMID- 26154263 TI - Antibacterial Properties and Mechanism of Activity of a Novel Silver-Stabilized Hydrogen Peroxide. AB - Huwa-San peroxide (hydrogen peroxide; HSP) is a NSF Standard 60 (maximum 8 mg/L( 1)) new generation peroxide stabilized with ionic silver suitable for continuous disinfection of potable water. Experiments were undertaken to examine the mechanism of HSP against planktonic and biofilm cultures of indicator bacterial strains. Contact/kill time (CT) relationships that achieve effective control were explored to determine the potential utility in primary disinfection. Inhibitory assays were conducted using both nutrient rich media and a medium based on synthetic wastewater. Assays were compared for exposures to three disinfectants (HSP, laboratory grade hydrogen peroxide (HP) and sodium hypochlorite) at concentrations of 20 ppm (therefore at 2.5 and 5 times the NSF limit for HP and sodium hypochlorite, respectively) and at pH 7.0 and 8.5 in dechlorinated tap water. HSP was found to be more or equally effective as hypochlorite or HP. Results from CT assays comparing HSP and HP at different bacterial concentrations with neutralization of residual peroxide with catalase suggested that at a high bacterial concentration HSP, but not HP, was protected from catalase degradation possibly through sequestration by bacterial cells. Consistent with this hypothesis, at a low bacterial cell density residual HSP was more effectively neutralized as less HSP was associated with bacteria and therefore accessible to catalase. Silver in HSP may facilitate this association through electrostatic interactions at the cell surface. This was supported by experiments where the addition of mono (K(+)) and divalent (Ca(+2)) cations (0.005-0.05M) reduced the killing efficacy of HSP but not HP. Experiments designed to distinguish any inhibitory effect of silver from that of peroxide in HSP were carried out by monitoring the metabolic activity of established P. aeruginosa PAO1 biofilms. Concentrations of 70-500 ppm HSP had a pronounced effect on metabolic activity while the equivalent concentrations of ionic silver (50- 375 ppb) had a negligible effect, demonstrating that the microbiocidal activity of HSP was due to peroxide rather than silver. Overall, it was found that the antimicrobial activity of HSP is enhanced over that of hydrogen peroxide; the presence of the ionic silver enhances interactions of HSP with the bacterial cell surface rather than acting directly as a biocide at the tested concentrations. PMID- 26154265 TI - Polyamine Triglycerides: Synthesis and Study of Their Potential in Lubrication, Neutralization, and Sequestration. AB - Renewable resources have evoked a new awakening in both scientific and industrial circles in the past decade. Vegetable oil is one category of renewables that is amenable as a source of new industrial products. Because the source feedstock, seeds, are environmentally friendly, the derivatized products from these at the end of their lifetime could also be benign when designed appropriately. Bioethanol and biodiesel are examples of biobased industrial products currently in the market place and have become resources for uplifting the rural economy. Biolubricants also are playing a more prominent role because they have become closely competitive with petroleum-based lubricants. These products are renewable because the crops from which the feedstuff for the biofuels and biolubricants are produced are grown annually in contrast to nonrenewable mineral sources. Added to their renewability is the inherent biodegradability of their end-use products after their useful lifetime. In a recent study of the lubricity characteristics of peracylated polyhydroxy milkweed oil, the derivatives were found to exhibit good oxidative stability as well as excellent antiwear properties. To further explore an expansion in the properties of such materials in lubrication and other applications, in this study the polyhydroxy (OH) moieties of derivatized milkweed triglycerides were replaced with -NHR groupings in the oil. In this process novel polyketo triglyceride intermediates leading to polyamine derivatives of the vegetable oil have been synthesized. The polyamine triglyceride markedly improved the stability of the parent oil to oxidative stress. It has also attenuated the extreme viscosity of the starting polyhydroxy oil to a more useful product that could be amenable for use as a lubricating agent, for example, hydraulic fluid. Both the polyketone and polyimine intermediates of the polyamine have chelating properties. The intermediates and the polyamine were characterized spectroscopically, tribologically, and rheologically for their intrinsic properties. PMID- 26154264 TI - Genomics and Machine Learning for Taxonomy Consensus: The Mycobacterium tuberculosis Complex Paradigm. AB - Infra-species taxonomy is a prerequisite to compare features such as virulence in different pathogen lineages. Mycobacterium tuberculosis complex taxonomy has rapidly evolved in the last 20 years through intensive clinical isolation, advances in sequencing and in the description of fast-evolving loci (CRISPR and MIRU-VNTR). On-line tools to describe new isolates have been set up based on known diversity either on CRISPRs (also known as spoligotypes) or on MIRU-VNTR profiles. The underlying taxonomies are largely concordant but use different names and offer different depths. The objectives of this study were 1) to explicit the consensus that exists between the alternative taxonomies, and 2) to provide an on-line tool to ease classification of new isolates. Genotyping (24 VNTR, 43-spacers spoligotypes, IS6110-RFLP) was undertaken for 3,454 clinical isolates from the Netherlands (2004-2008). The resulting database was enlarged with African isolates to include most human tuberculosis diversity. Assignations were obtained using TB-Lineage, MIRU-VNTRPlus, SITVITWEB and an algorithm from Borile et al. By identifying the recurrent concordances between the alternative taxonomies, we proposed a consensus including 22 sublineages. Original and consensus assignations of the all isolates from the database were subsequently implemented into an ensemble learning approach based on Machine Learning tool Weka to derive a classification scheme. All assignations were reproduced with very good sensibilities and specificities. When applied to independent datasets, it was able to suggest new sublineages such as pseudo-Beijing. This Lineage Prediction tool, efficient on 15-MIRU, 24-VNTR and spoligotype data is available on the web interface "TBminer." Another section of this website helps summarizing key molecular epidemiological data, easing tuberculosis surveillance. Altogether, we successfully used Machine Learning on a large dataset to set up and make available the first consensual taxonomy for human Mycobacterium tuberculosis complex. Additional developments using SNPs will help stabilizing it. PMID- 26154266 TI - The Pied Piper: A Parasitic Beetle's Melodies Modulate Ant Behaviours. AB - Ants use various communication channels to regulate their social organisation. The main channel that drives almost all the ants' activities and behaviours is the chemical one, but it is long acknowledged that the acoustic channel also plays an important role. However, very little is known regarding exploitation of the acoustical channel by myrmecophile parasites to infiltrate the ant society. Among social parasites, the ant nest beetles (Paussus) are obligate myrmecophiles able to move throughout the colony at will and prey on the ants, surprisingly never eliciting aggression from the colonies. It has been recently postulated that stridulatory organs in Paussus might be evolved as an acoustic mechanism to interact with ants. Here, we survey the role of acoustic signals employed in the Paussus beetle-Pheidole ant system. Ants parasitised by Paussus beetles produce caste-specific stridulations. We found that Paussus can "speak" three different "languages", each similar to sounds produced by different ant castes (workers, soldiers, queen). Playback experiments were used to test how host ants respond to the sounds emitted by Paussus. Our data suggest that, by mimicking the stridulations of the queen, Paussus is able to dupe the workers of its host and to be treated as royalty. This is the first report of acoustic mimicry in a beetle parasite of ants. PMID- 26154267 TI - Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia. AB - CONTEXT: Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia. OBJECTIVE: The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia. METHODS: Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively. RESULTS: The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug. CONCLUSION: It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia. PMID- 26154269 TI - Correction Announcement. AB - [This corrects the article on p. 2236 in vol. 8, PMID: 25206533.]. PMID- 26154271 TI - Computational Study of the Clustering of a Cyclohexene Autoxidation Product C6H8O7 with Itself and Sulfuric Acid. AB - We investigate the molecular interactions between sulfuric acid and a recently reported C6H8O7 ketodiperoxy acid formed through autoxidation from cyclohexene and ozone. Structurally similar but larger ELVOC (extremely low volatility organic compound) products formed from autoxidation of monoterpenes are believed to play a major role in the formation and early growth of atmospheric aerosol particles. Utilizing density functional theory geometries, with a DLPNO CCSD(T)/def2-QZVPP single point energy correction, the stepwise Gibbs free energies of formation have been calculated, and the stabilities of the molecular clusters have been evaluated. C6H8O7 interacts weakly with both itself and sulfuric acid, with standard free energies of formation (DeltaG at 298 K and 1 atm) around or above 0 kcal/mol. This is due to the presence of strong intramolecular hydrogen bonds in the peroxyacid groups of C6H8O7. These stabilize the isolated molecule with respect to its clusters, and lead to unfavorable interaction energies. The addition of sulfuric acid to clusters containing C6H8O7 is somewhat more favorable, but the formed clusters are still far more likely to evaporate than to grow further in atmospheric conditions. These findings indicate that the O/C ratio cannot exclusively be used as a proxy for volatility in atmospheric new particle formation involving organic compounds. The specific molecular structure, and especially the number of strong hydrogen binding moieties, are equally important. The interaction between the C6H8O7 compound and aqueous phase sulfate ions indicates that ELVOC-type compounds can contribute to aerosol mass by effectively partitioning into the condensed phase. PMID- 26154268 TI - GDF-15 secreted from human umbilical cord blood mesenchymal stem cells delivered through the cerebrospinal fluid promotes hippocampal neurogenesis and synaptic activity in an Alzheimer's disease model. AB - Our previous studies demonstrated that transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the hippocampus of a transgenic mouse model of Alzheimer's disease (AD) reduced amyloid-beta (Abeta) plaques and enhanced cognitive function through paracrine action. Due to the limited life span of hUCB-MSCs after their transplantation, the extension of hUCB MSC efficacy was essential for AD treatment. In this study, we show that repeated cisterna magna injections of hUCB-MSCs activated endogenous hippocampal neurogenesis and significantly reduced Abeta42 levels. To identify the paracrine factors released from the hUCB-MSCs that stimulated endogenous hippocampal neurogenesis in the dentate gyrus, we cocultured adult mouse neural stem cells (NSCs) with hUCB-MSCs and analyzed the cocultured media with cytokine arrays. Growth differentiation factor-15 (GDF-15) levels were significantly increased in the media. GDF-15 suppression in hUCB-MSCs with GDF-15 small interfering RNA reduced the proliferation of NSCs in cocultures. Conversely, recombinant GDF-15 treatment in both in vitro and in vivo enhanced hippocampal NSC proliferation and neuronal differentiation. Repeated administration of hUBC-MSCs markedly promoted the expression of synaptic vesicle markers, including synaptophysin, which are downregulated in patients with AD. In addition, in vitro synaptic activity through GDF-15 was promoted. Taken together, these results indicated that repeated cisterna magna administration of hUCB-MSCs enhanced endogenous adult hippocampal neurogenesis and synaptic activity through a paracrine factor of GDF 15, suggesting a possible role of hUCB-MSCs in future treatment strategies for AD. PMID- 26154270 TI - Angiotensin type 1a receptor deficiency decreases amyloid beta-protein generation and ameliorates brain amyloid pathology. AB - Alzheimer's disease is characterized by neuronal loss and cerebral accumulation of amyloid-beta protein (Abeta) and lowering the generation of Abeta is a pivotal approach in the strategy of Alzheimer's disease treatment. Midlife hypertension is a major risk factor for the future onset of sporadic Alzheimer's disease and the use of some antihypertensive drugs may decrease the incidence of Alzheimer's disease. However, it is largely unknown how the blood pressure regulation system is associated with the pathogenesis of Alzheimer's disease. Here we found that the deficiency of angiotensin type 1a receptor (AT1a), a key receptor for regulating blood pressure, significantly decreased Abeta generation and amyloid plaque formation in a mouse model of Alzheimer's disease. The lack of AT1a inhibited the endocleavage of presenilin-1 (PS1), which is essential for gamma secretase complex formation and Abeta generation. Notably, the ligand of AT1a, angiotensin II, enhanced Abeta generation, PS1 endocleavage and gamma-secretase complex formation. Our results suggest that AT1a activation is closely associated with Abeta generation and brain amyloid accumulation by regulating gamma secretase complex formation. Thus, removal of life style factors or stresses that stimulate AT1a to elevate blood pressure may decrease Abeta generation and brain amyloid accumulation, thereby preventing the pathogenesis of Alzheimer's disease. PMID- 26154272 TI - Vaginal atrophy and disease susceptibility: the role of leukocytes. PMID- 26154273 TI - MicroRNA-125a-5p induces mouse granulosa cell apoptosis by targeting signal transducer and activator of transcription 3. AB - OBJECTIVE: Premature ovarian failure, a reproductive dysfunction characterized by follicle loss leads to premature menopause. Apoptosis of granulosa cells may be responsible for the associated follicle depletion. MicroRNAs are expressed abundantly in granulosa cells and play an important role in follicular atresia. Evidence suggests that signal transducer and activator of transcription 3 (STAT3) is involved in follicle growth and female fertility. METHODS: We incubated cultured mouse granulosa cells (mGCs) with increasing doses of cisplatin (CP) for varying periods. Cell proliferation and apoptosis were measured by Cell Counting Kit-8 assay, flow cytometry, and protein expression of cleaved caspase-3. Western blot analysis was used to assess STAT3 and phospho-STAT3 after mGCs were transfected with a microRNA-125a-5p (miR-125a-5p) mimic and a miR-125a-5p inhibitor, respectively. Luciferase reporter assay was conducted to determine the relationship between miR-125a-5p and STAT3. RESULTS: CP reduced mGC viability, progesterone levels, and estradiol levels. miR-125a-5p was up-regulated in CP treated mGCs, whereas STAT3 was down-regulated. Increased apoptosis and cleaved caspase-3 were observed in mGCs transfected with a miR-125a-5p mimic or STAT3 interference fragment. Protein expression of STAT3 and phospho-STAT3 was up regulated or down-regulated when transfected with a miR-125a-5p inhibitor or miR 125a-5p mimic, respectively. Luciferase reporter assays indicated that miR-125a 5p targets the 3' untranslated region of STAT3. CONCLUSIONS: Overexpression of miR-125a-5p promotes mGC apoptosis by targeting STAT3. Our findings imply the important role of miR-125a-5p in the pathogenesis of premature ovarian failure. PMID- 26154274 TI - Association between nonalcoholic fatty liver disease and coronary artery calcification in postmenopausal women. AB - OBJECTIVE: Cardiovascular disease is a leading cause of death in postmenopausal women, and nonalcoholic fatty liver disease (NAFLD) has been known to be associated with cardiovascular disease. However, little information regarding the relationship between NAFLD and coronary artery calcification (CAC) in postmenopausal women is available. The aim of this study was to investigate the association between NAFLD and CAC in postmenopausal women. METHODS: Among 4,377 participants who underwent cardiac computed tomography in a health promotion center, 919 postmenopausal women were enrolled. Anthropometric profiles and multiple cardiovascular risk factors were measured. NAFLD was measured by ultrasonography, and CAC was evaluated by cardiac computed tomography. Odds ratios and 95% CI for the presence of CAC, by severity of fatty liver disease, were estimated using logistic regression. RESULTS: Women were stratified into three groups by severity of NAFLD. There were significant differences in cardiovascular parameters among the groups, and prevalence of CAC significantly increased with severity of NAFLD. On logistic regression analysis after adjustment for multiple risk factors, the odds ratios for the prevalence of CAC were as follows (P < 0.05): no NAFLD, 1.0; mild NAFLD, 1.34 (95% CI, 0.92-2.16); moderate to severe NAFLD, 1.83 (95% CI, 1.06-3.16). However, this association was attenuated after adjustment for insulin resistance (P = 0.16). CONCLUSIONS: There is a significant correlation between NAFLD and prevalence of CAC, but NAFLD is not an independent factor for coronary atherosclerosis in postmenopausal women. PMID- 26154275 TI - Ospemifene should be used as a single agent without progestin in postmenopausal women with an intact uterus. PMID- 26154276 TI - Sleep and menopause: a narrative review. AB - OBJECTIVE: Our overall aim-through a narrative review-is to critically profile key extant evidence of menopause-related sleep, mostly from studies published in the last decade. METHODS: We searched the database PubMed using selected Medical Subject Headings for sleep and menopause (n = 588 articles). Using similar headings, we also searched the Cochrane Library (n = 1), Embase (n = 449), Cumulative Index to Nursing and Allied Health Literature (n = 163), Web of Science (n = 506), and PsycINFO (n = 58). Articles deemed most related to the purpose were reviewed. RESULTS: Results were articulated with interpretive comments according to evidence of sleep quality (self-reported) and sleep patterns (polysomnography and actigraphy) impact as related to reproductive aging and in the context of vasomotor symptoms (VMS; self-reported), vasomotor activity (VMA) events (recorded skin conductance), depressed mood, and ovarian hormones. CONCLUSIONS: Predominantly, the menopausal transition conveys poor sleep beyond anticipated age effects. Perceptions of sleep are not necessarily translatable from detectable physical sleep changes and are probably affected by an emotional overlay on symptoms reporting. Sleep quality and pattern changes are mostly manifest in wakefulness indicators, but sleep pattern changes are not striking. Likely contributing are VMS of sufficient frequency/severity and bothersomeness, probably with a sweating component. VMA events influence physical sleep fragmentation but not necessarily extensive sleep loss or sleep architecture changes. Lack of robust connections between perceived and recorded sleep (and VMA) could be influenced by inadequate detection. There is a need for studies of women in well-defined menopausal transition stages who have no sleep problems, accounting for sleep-related disorders, mood, and other symptoms, with attention to VMS dimensions, distribution of VMS during night and day, and advanced measurement of symptoms and physiologic manifestations. PMID- 26154277 TI - Controlled synthesis of uniform palladium nanoparticles on novel micro-porous carbon as a recyclable heterogeneous catalyst for the Heck reaction. AB - Novel dual-porous carbon-supported palladium nanoparticle (Pd NP) catalysts were prepared by sequential carbonization and reduction of microporous organic polymer encaged PdCl2. The diverse pore structure of microporous organic polymers provides a reservoir for the palladium precursors and prevents Pd NPs from sintering during the carbonization and reaction. The microporous structure has a significant effect on the size and dispersion of palladium NPs. The average size of the Pd NPs (in the range of 4-6 nm) was tuned by changing the pore size distribution and the carbonization temperature. The resulting carbon-supported Pd NPs were characterized by TEM, BET, XRD, and XPS and the Pd loading was calculated by AAS. The encaged Pd NP catalysts prepared by this methodology exhibited outstanding stability and reusability in the Heck reaction and could be reused at least 10 times without appreciable loss of activity. PMID- 26154278 TI - Influence of high-fat diet on gut microbiota: a driving force for chronic disease risk. AB - PURPOSE OF REVIEW: This review will examine the recent scientific literature surrounding high-fat-diet (HFD)-induced alterations in gut microbiota and subsequent development of obesity and chronic disease risk. RECENT FINDINGS: Excessive consumption of HFDs has undoubtedly contributed to the obesity epidemic. The mechanisms responsible for this relationship are, however, likely to be more complex than the simple concept of energy balance. In fact, emerging literature has implicated HFD-induced alterations in gut microbiota in the obesity epidemic. HFD consumption generally leads to a decrease in Bacteroidetes and an increase in Firmicutes, alterations that have been associated with obesity and subsequent development of chronic diseases. Potential mechanisms for this effect include an improved capacity for energy harvest and storage, and enhanced gut permeability and inflammation. We highlight the most important recent advances linking HFD-induced dysbiosis to obesity, explore the possible mechanisms for this effect, examine the implications for disease development, and evaluate the possibility of therapeutic targeting of the gut microbiome to reduce obesity. SUMMARY: A better understanding of the mechanisms linking HFD to alterations in gut microbiota is necessary to allow for the regulation of dysbiosis and ensuing promotion of antiobesity effects. PMID- 26154279 TI - Intestine, immunity, and parenteral nutrition in an era of preferred enteral feeding. AB - PURPOSE OF REVIEW: To review the benefits of enteral nutrition in contrast to the inflammatory consequences of administration of parenteral nutrition and enteral deprivation. To present the most recent evidence for the mechanisms of these immunologic changes and discuss potential areas for modification to decrease infectious complications of its administration. RECENT FINDINGS: There is significant data supporting the early initiation of enteral nutrition in both medical and surgical patients unable to meet their caloric goals via oral intake alone. Despite the preference for enteral nutrition, some patients are unable to utilize their gut for nutritious gain and therefore require parenteral nutrition administration, along with its infectious complications. The mechanisms behind these complications are multifactorial and have yet to be fully elucidated. Recent study utilizing both animal and human models has provided further information regarding parenteral nutrition's deleterious effect on intestinal epithelial barrier function along with the complications associated with enterocyte deprivation. SUMMARY: Changes associated with parenteral nutrition administration and enteral deprivation are complex with multiple potential areas for modification to allow for safer administration. Recent discovery of the mechanisms behind these changes present exciting areas for future study as to make parenteral nutrition administration in the enterally deprived patient safer. PMID- 26154280 TI - Two elephants in the room: new hybrid nuclear magnetic resonance and mass spectrometry approaches for metabolomics. AB - PURPOSE OF REVIEW: This review describes some of the advances made over the past year in NMR-based metabolomics for the elucidation of known and unknown compounds, including new ways of how to combine this information with high resolution mass spectrometry. RECENT FINDINGS: A new method allows the back calculation of mass spectra from NMR spectra that have been queried against databases improving the accuracy of the identified compounds by validation and consistency analysis. For the de-novo characterization of unknown compounds, an algorithm has been introduced that predicts all viable NMR spectra from accurate masses allowing, by comparison with experimental NMR data, the determination of the structures of new metabolites in complex mixtures. SUMMARY: Recent advances in NMR and mass spectrometry-based metabolomics and their synergistic use promises to significantly improve metabolomics sample characterization both in terms of identification and quantitation, and accelerate metabolite discovery. PMID- 26154281 TI - The diversity of methods and instruments in nutrition reflects the broad scope of the discipline. PMID- 26154282 TI - Temporal Trends and Treatment Outcomes of Flexible Ureteroscopy for Lower Pole Stones in a Tertiary Referral Stone Center. AB - INTRODUCTION: To evaluate trends in efficacy and safety of flexible ureteroscopy (fURS) for the treatment of lower pole stones (LPS) over a 6-year period and to compare the annual outcomes after one fURS procedure retrospectively. PATIENTS AND METHODS: Four hundred nine patients were treated for pure LPS. An analysis of the annual outcomes regarding patient characteristics, operative parameters, stone-free rates (SFRs), and complication rates (CRs) was performed. The SFR was stratified according to stone size and number of stones per patient. Patient data are expressed as mean+/-standard deviation. RESULTS: There were no annual differences regarding age, body-mass index, stone size (7.09+/-4.31 mm), number of stones per patient (1.66+/-2.86), operative time (52.93+/-33.58 minutes), use of postoperative stents (59.2%), and the Ho:YAG laser lithotripsy rate (49.4%) during the 6-year period. Total primary SFR (annual range) of 97.6% (88.2%-100%), 89.1% (82.9%-96.3%), 71% (60%-78.6%) for urinary calculi <5 mm (3.43+/-0.78 mm), 5-9 mm (6.69+/-1.34 mm), and >=10 mm (13.09+/-6.02 mm) could be demonstrated over the 6-year period. The total SFR differed significantly between urinary calculi <5 mm, 5-9 mm, and those >=10 mm (p<0.0179). The SFR (annual range) decreased from 90% (86.2%-95.4%) in patients with 1 stone to 84.1% (60%-100%) in those with >=3 stones. Perioperative complications (annual range) occurred in 9.7% (6% 13.6%) of the patients (Clavien I 5.1% [1.2%-8.6%], Clavien II 2% [0%-4.9%], Clavien IIIa 0.9% [0%-3.4%], Clavien IIIb 1.7% [1.2%-4.8%]) without differences in the annual CR. CONCLUSIONS: fURS is a safe and efficacious procedure for the treatment of LPS with high primary SFR and low CR. fURS in larger LPS (>=10 mm) is associated with the risk for staged procedures. PMID- 26154284 TI - Spontaneous Giving under Structural Inequality: Intuition Promotes Cooperation in Asymmetric Social Dilemmas. AB - The present research investigates the role of intuitive mental processing on cooperation in experimental games involving structural inequality. Results from an experiment using conceptual priming to induce intuitive mental processing provide the first evidence that cooperation is promoted by intuition in an asymmetric context that distributes the gains from cooperation unequally among a group. Therefore, the results extend our understanding of the cognitive underpinnings of human cooperation by demonstrating the robustness of intuitive cooperation in games involving structural inequality regarding asymmetric gains from cooperation. Additionally, the results provide the first successful conceptual replication of the intuition-cooperation link using conceptual priming, therefore also contributing to the debate about the validity of previous research in other contexts. Taken together, the present research contributes to the literature on psychological and institutional mechanisms that promote cooperation. PMID- 26154283 TI - Burn Injury Alters the Intestinal Microbiome and Increases Gut Permeability and Bacterial Translocation. AB - Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces a dramatic dysbiosis of the intestinal microbiome of both humans and mice and allows for similar overgrowths of Gram-negative aerobic bacteria. Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites. This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host. PMID- 26154285 TI - Variation in Foot Strike Patterns among Habitually Barefoot and Shod Runners in Kenya. AB - Runners are often categorized as forefoot, midfoot or rearfoot strikers, but how much and why do individuals vary in foot strike patterns when running on level terrain? This study used general linear mixed-effects models to explore both intra- and inter-individual variations in foot strike pattern among 48 Kalenjin speaking participants from Kenya who varied in age, sex, body mass, height, running history, and habitual use of footwear. High speed video was used to measure lower extremity kinematics at ground contact in the sagittal plane while participants ran down 13 meter-long tracks with three variables independently controlled: speed, track stiffness, and step frequency. 72% of the habitually barefoot and 32% of the habitually shod participants used multiple strike types, with significantly higher levels of foot strike variation among individuals who ran less frequently and who used lower step frequencies. There was no effect of sex, age, height or weight on foot strike angle, but individuals were more likely to midfoot or forefoot strike when they ran on a stiff surface, had a high preferred stride frequency, were habitually barefoot, and had more experience running. It is hypothesized that strike type variation during running, including a more frequent use of forefoot and midfoot strikes, used to be greater before the introduction of cushioned shoes and paved surfaces. PMID- 26154286 TI - Resuscitation Using Liposomal Vasopressin in an Animal Model of Uncontrolled Hemorrhagic Shock. AB - BACKGROUND: Current research suggests that administration of vasopressin to patients with uncontrolled hemorrhagic shock (UHS) can avoid the detrimental effects associated with aggressive fluid resuscitation. However, vasopressin has a short half-life of 10~35 minutes in in vivo use and precludes its use in the pre-hospital setting. To increase the half-life of vasopressin, we proposed to synthesize liposome-encapsulated vasopressin and test it in a rat model of UHS. METHODS: The film hydration method was used to prepare liposomal vasopressin consisting of: Dipalmitoylphosphatidylcholine, cholesterol, and dipalmitoyl phosphatidylethanolamine (20:20:1 mole ratio). 42 rats were subjected to UHS and randomly received 5 different treatments (vasopressin, liposomal vasopressin, lactate ringer (LR), liposome only and sham). Outcome of UHS were measured using 4 common prognostic tests: mean arterial pressure (MAP), serum lactate level, inflammatory profile and pulmonary edema. RESULTS: The dynamic light scattering results confirmed that we had prepared a successful liposomal vasopressin complex. Comparing the serum vasopressin concentration of liposomal vasopressin and vasopressin treated animals by ELISA, we found that the concentration of vasopressin for the liposomal vasopressin treated group is higher at 60 minutes. However, there was no significant difference between the MAP profile of rats treated with vasopressin and liposomal vasopressin in UHS. We also observed that animals treated with liposomal vasopressin performed indifferently to vasopressin treated rats in serum lactate level, inflammatory profile and edema profile. For most of our assays, the liposome only control behaves similarly to LR resuscitation in UHS rats. CONCLUSION: We have synthesized a liposomal vasopressin complex that can prolong the serum concentration of vasopressin in a rat model of UHS. Although UHS rats treated with either liposomal vasopressin or vasopressin showed no statistical differences, it would be worthwhile to repeat the experiments with different liposomal compositions. PMID- 26154287 TI - Evidence of Experimental Bias in the Life Sciences: Why We Need Blind Data Recording. AB - Observer bias and other "experimenter effects" occur when researchers' expectations influence study outcome. These biases are strongest when researchers expect a particular result, are measuring subjective variables, and have an incentive to produce data that confirm predictions. To minimize bias, it is good practice to work "blind," meaning that experimenters are unaware of the identity or treatment group of their subjects while conducting research. Here, using text mining and a literature review, we find evidence that blind protocols are uncommon in the life sciences and that nonblind studies tend to report higher effect sizes and more significant p-values. We discuss methods to minimize bias and urge researchers, editors, and peer reviewers to keep blind protocols in mind. PMID- 26154288 TI - The Brazilian Version of the Edmonton Symptom Assessment System (ESAS) Is a Feasible, Valid and Reliable Instrument for the Measurement of Symptoms in Advanced Cancer Patients. AB - PURPOSES: To develop and validate a Portuguese version of the Edmonton Symptom Assessment System (ESAS) in Brazilian patients with advanced cancer. METHODS: The ESAS was translated and then back translated into Portuguese in accordance with international guidelines. The final version was approved by an Expert Committee after pilot testing on 24 advanced cancer patients. Subsequently, we evaluated the time to complete the assessment, the number of unanswered items, internal consistency, convergent validity, and known-group validity in a sample of 249 advanced cancer patients who completed the ESAS along with the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), Hospital Anxiety and Depression Scale (HADS), and Epworth Sleepiness Scale (ESS). A total of 90 clinically stable patients were retested after 4 to 96 hours (test-retest reliability), and 80 patients answered the ESAS after 21 (+/- 7) days to measure scale responsiveness using an anchor based method. RESULTS: The ESAS was completed in a mean time of only 2.2 minutes. The internal consistency was good (Cronbach's alpha = 0.861), and the removal of single items did not change the overall alpha value. For convergent validity, Spearman's correlation coefficients between the ESAS symptom scores and the corresponding EORTC QLQ-C30 and ESS symptom scores ranged between 0.520 (95% CI = 0.424-0.605) and 0.814 (95% CI = 0.760-0.856), indicating moderate to strong correlations. Test-retest reliability values were considered adequate, with intraclass correlation coefficients ranging from 0.758 (95% CI = 0.627-0.843) to 0.939 (95% CI = 0.905-0.960). CONCLUSIONS: ESAS is a feasible, valid and reliable multi-symptom assessment instrument for use in Brazil. PMID- 26154289 TI - Effects of Health-Related Food Taxes and Subsidies on Mortality from Diet-Related Disease in New Zealand: An Econometric-Epidemiologic Modelling Study. AB - BACKGROUND: Health-related food taxes and subsidies may promote healthier diets and reduce mortality. Our aim was to estimate the effects of health-related food taxes and subsidies on deaths prevented or postponed (DPP) in New Zealand. METHODS: A macrosimulation model based on household expenditure data, demand elasticities and population impact fractions for 18 diet-related diseases was used to estimate effects of five tax and subsidy regimens. We used price elasticity values for 24 major commonly consumed food groups in New Zealand, and food expenditure data from national Household Economic Surveys. Changes in mortality from cardiovascular disease, cancer, diabetes and other diet-related diseases were estimated. FINDINGS: A 20% subsidy on fruit and vegetables would result in 560 (95% uncertainty interval, 400 to 700) DPP each year (1.9% annual all-cause mortality). A 20% tax on major dietary sources of saturated fat would result in 1,500 (950 to 2,100) DPP (5.0%), and a 20% tax on major dietary sources of sodium would result in 2,000 (1300 to 2,700) DPP (6.8%). Combining taxes on saturated fat and sodium with a fruit and vegetable subsidy would result in 2,400 (1,800 to 3,000) DPP (8.1% mortality annually). A tax on major dietary sources of greenhouse gas emissions would generate 1,200 (750 to 1,700) DPP annually (4.0%). Effects were similar or greater for Maori and low-income households in relative terms. CONCLUSIONS: Health-related food taxes and subsidies could improve diets and reduce mortality from diet-related disease in New Zealand. Our study adds to the growing evidence base suggesting food pricing policies should improve population health and reduce inequalities, but there is still much work to be done to improve estimation of health impacts. PMID- 26154291 TI - Washington Gains Additional Insight into Nursing Home Problems. PMID- 26154292 TI - Segregation of the hereditary thrombopathia-associated polymorphism in polled German Fleckvieh cattle. PMID- 26154290 TI - Screening for FtsZ Dimerization Inhibitors Using Fluorescence Cross-Correlation Spectroscopy and Surface Resonance Plasmon Analysis. AB - FtsZ is an attractive target for antibiotic research because it is an essential bacterial cell division protein that polymerizes in a GTP-dependent manner. To find the seed chemical structure, we established a high-throughput, quantitative screening method combining fluorescence cross-correlation spectroscopy (FCCS) and surface plasmon resonance (SPR). As a new concept for the application of FCCS to polymerization-prone protein, Staphylococcus aureus FtsZ was fragmented into the N-terminal and C-terminal, which were fused with GFP and mCherry (red fluorescent protein), respectively. By this fragmentation, the GTP-dependent head-to-tail dimerization of each fluorescent labeled fragment of FtsZ could be observed, and the inhibitory processes of chemicals could be monitored by FCCS. In the first round of screening by FCCS, 28 candidates were quantitatively and statistically selected from 495 chemicals determined by in silico screening. Subsequently, in the second round of screening by FCCS, 71 candidates were also chosen from 888 chemicals selected via an in silico structural similarity search of the chemicals screened in the first round of screening. Moreover, the dissociation constants between the highest inhibitory chemicals and Staphylococcus aureus FtsZ were determined by SPR. Finally, by measuring the minimum inhibitory concentration, it was confirmed that the screened chemical had antibacterial activity against Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA). PMID- 26154293 TI - Cranial Anatomy of Wendiceratops pinhornensis gen. et sp. nov., a Centrosaurine Ceratopsid (Dinosauria: Ornithischia) from the Oldman Formation (Campanian), Alberta, Canada, and the Evolution of Ceratopsid Nasal Ornamentation. AB - The fossil record of ceratopsid dinosaurs between the occurrence of their proximate sister taxa in the Turonian and the beginning of their well-documented radiation from the late Campanian of North America onwards (approximately 90 and 77 Ma) is poor, with only seven taxa described from this early period in their evolution. We describe a new taxon of a highly adorned basal centrosaurine, Wendiceratops pinhornensis gen. et sp. nov., from the lower part of the Oldman Formation (middle Campanian, approximately 78-79 Ma), Alberta, Canada. Over 200 bones derived from virtually all parts of the skeleton, including multiple well preserved specimens of the diagnostic parietosquamosal frill, were collected from a medium-density monodominant bonebed, making the new taxon one of the best represented early ceratopsids. The new taxon is apomorphic in having epiparietals at loci 2 and 3 developed as broad-based, pachyostotic processes that are strongly procurved anterodorsally to overhang the posterior and lateral parietal rami, and an ischium with a broad, rectangular distal terminus. Although the morphology of the nasal is incompletely known, Wendiceratops is inferred to have a large, upright nasal horn located close to the orbits, which represents the oldest occurrence of this feature in Ceratopsia. Given the phylogenetic position of the new taxon within Centrosaurinae, a enlarged nasal horn is hypothesized to have arisen independently at least twice in ceratopsid evolution. PMID- 26154294 TI - Bare Metal Stents Versus Drug Eluting Stents: Where Do We Stand in 2015? AB - OPINION STATEMENT: The development of bare metal stent (BMS) was a major advancement over plain old balloon angioplasty (POBA) in the management of symptomatic coronary artery disease. BMS prevented restenosis by attenuating early arterial recoil and contraction; both seen commonly after POBA. However, the rate of clinically indicated target lesion repeat revascularization due to a process of in-stent restenosis (ISR) at 1 year remained relatively high (10 to 20 %), often due to excessive neointimal growth (Fischman et al. N Engl J Med. 331:496, 1994; Serruys et al. N Engl J Med. 331:489, 1994; Cutlip et al. J Am Coll Cardiol 40:2082, 2002). Stents with drug elution technology (DES) were developed to reduce the relatively high rate of ISR and subsequent repeat revascularization seen with BMS. Clinical trials have confirmed a reduction of as much as 50 to 70 % in target lesion revascularization by DES compared to BMS. These findings have led to the preferential use of DES in the majority of percutaneous coronary intervention (PCI). However, as DES require a longer period of dual antiplatelet therapy (DAPT) to prevent stent thrombosis, DES are not appropriate for all patients. PMID- 26154295 TI - The Role of Bioacoustic Signals in Koala Sexual Selection: Insights from Seasonal Patterns of Associations Revealed with GPS-Proximity Units. AB - Despite being a charismatic and well-known species, the social system of the koala (Phascolarctos cinereus--the only extant member of the family Phascolarctidae) is poorly known and much of the koala's sociality and mating behaviors remain un-quantified. We evaluated these using proximity logging-GPS enabled tracking collars on wild koalas and discuss their implications for the mating system of this species. The frequency and duration of male-female encounters increased during the breeding season, with male-male encounters quite uncommon, suggesting little direct mating competition. By comparison, female female interactions were very common across both seasons. Body mass of males was not correlated with their interactions with females during the breeding season, although male size is associated with a variety of acoustic parameters indicating individuality. We hypothesise that vocal advertising reduces the likelihood of male-male encounters in the breeding season while increasing the rate of male female encounters. We suggest that male mating-season bellows function to reduce physical confrontations with other males allowing them to space themselves apart, while, at the same time, attracting females. We conclude that indirect male-male competition, female mate choice, and possibly female competition, mediate sexual selection in koalas. PMID- 26154297 TI - Stability of Neuronal Networks with Homeostatic Regulation. AB - Neurons are equipped with homeostatic mechanisms that counteract long-term perturbations of their average activity and thereby keep neurons in a healthy and information-rich operating regime. While homeostasis is believed to be crucial for neural function, a systematic analysis of homeostatic control has largely been lacking. The analysis presented here analyses the necessary conditions for stable homeostatic control. We consider networks of neurons with homeostasis and show that homeostatic control that is stable for single neurons, can destabilize activity in otherwise stable recurrent networks leading to strong non-abating oscillations in the activity. This instability can be prevented by slowing down the homeostatic control. The stronger the network recurrence, the slower the homeostasis has to be. Next, we consider how non-linearities in the neural activation function affect these constraints. Finally, we consider the case that homeostatic feedback is mediated via a cascade of multiple intermediate stages. Counter-intuitively, the addition of extra stages in the homeostatic control loop further destabilizes activity in single neurons and networks. Our theoretical framework for homeostasis thus reveals previously unconsidered constraints on homeostasis in biological networks, and identifies conditions that require the slow time-constants of homeostatic regulation observed experimentally. PMID- 26154298 TI - Rituximab for sight-threatening refractory pediatric Vogt-Koyanagi-Harada disease. AB - Rituximab was trialed in a refractory Vogt-Koyanagi-Harada disease (VKH). A 10 year-old girl with panuveitis recalcitrant to treatment, including corticosteroids, was diagnosed with VKH 20 months later. Following rituximab at 0, 1, 6, and 18 months, response was favorable after the second dose, usual life activity resumed after the third dose (uveitis was inactivated and vision improved), and eyes stabilized 9 months after the fourth dose. Rituximab is effective in the treatment and long-term control of advanced, pediatric VKH. PMID- 26154296 TI - The Role of alpha-CTD in the Genome-Wide Transcriptional Regulation of the Bacillus subtilis Cells. AB - The amino acid sequence of the RNA polymerase (RNAP) alpha-subunit is well conserved throughout the Eubacteria. Its C-terminal domain (alpha-CTD) is important for the transcriptional regulation of specific promoters in both Escherichia coli and Bacillus subtilis, through interactions with transcription factors and/or a DNA element called the "UP element". However, there is only limited information regarding the alpha-CTD regulated genes in B. subtilis and the importance of this subunit in the transcriptional regulation of B. subtilis. Here, we established strains and the growth conditions in which the alpha-subunit of RNAP was replaced with a C-terminally truncated version. Transcriptomic and ChAP-chip analyses revealed that alpha-CTD deficiency reduced the transcription and RNAP binding of genes related to the utilization of secondary carbon sources, transition state responses, and ribosome synthesis. In E. coli, it is known that alpha-CTD also contributes to the expression of genes related to the utilization of secondary carbon sources and ribosome synthesis. Our results suggest that the biological importance of alpha-CTD is conserved in B. subtilis and E. coli, but that its specific roles have diversified between these two bacteria. PMID- 26154299 TI - Simultaneous Removal of NO and Hg(0) from Flue Gas over Mn-Ce/Ti-PILCs. AB - A series of Mn-Ce/Ti-PILCs (PILCs, pillared interlayered clays) catalysts were prepared via impregnation method in simultaneous removal of NO and elemental mercury in simulated flue gas. The physicochemical properties of these catalysts have been examined by some characterization methods, such as H2-TPR, nitrogen adsorption, XRD and XPS. Mn(6%)-Ce(6%)/Ti-PILCs exhibited superior NO conversion (>95%) and Hg(0) removal efficiency (>90%) at low temperature (250 degrees C). The results indicated that the elemental mercury had little impact on NO removal efficiency, while the presence of NH3 and NO in SCR system inhibited the Hg(0) removal. NO and Hg(0) removal activity was strongly affected by the transform between surface adsorbed oxygen and lattice oxygen. The species ratio of Mn(4+)/Mn(3+) and Ce(4+)/Ce(3+) on the catalyst surface contributed to the NO conversions and Hg(0) removal. Mn-Ce/Ti-PILCs displayed a broad prospect for controlling the emission of NO and mercury. On the basis of the results obtained, a mechanism for the simultaneous removal of NO and Hg(0) was proposed for the Mn Ce/Ti-PILCs catalysts: -NH2 + NO -> N2 + H2O, -OH + 1/2 Hg(ad) ->1/2 HgO + 1/2 H2O. PMID- 26154300 TI - Comparative Metagenomic Profiling of Symbiotic Bacterial Communities Associated with Ixodes persulcatus, Ixodes pavlovskyi and Dermacentor reticulatus Ticks. AB - Ixodes persulcatus, Ixodes pavlovskyi, and Dermacentor reticulatus ticks inhabiting Western Siberia are responsible for the transmission of a number of etiological agents that cause human and animal tick-borne diseases. Because these ticks are abundant in the suburbs of large cities, agricultural areas, and popular tourist sites and frequently attack people and livestock, data regarding the microbiomes of these organisms are required. Using metagenomic 16S profiling, we evaluate bacterial communities associated with I. persulcatus, I. pavlovskyi, and D. reticulatus ticks collected from the Novosibirsk region of Russia. A total of 1214 ticks were used for this study. DNA extracted from the ticks was pooled according to tick species and sex. Sequencing of the V3-V5 domains of 16S rRNA genes was performed using the Illumina Miseq platform. The following bacterial genera were prevalent in the examined communities: Acinetobacter (all three tick species), Rickettsia (I. persulcatus and D. reticulatus) and Francisella (D. reticulatus). B. burgdorferi sensu lato and B. miyamotoi sequences were detected in I. persulcatus and I. pavlovskyi but not in D. reticulatus ticks. The pooled samples of all tick species studied contained bacteria from the Anaplasmataceae family, although their occurrence was low. DNA from A. phagocytophilum and Candidatus Neoehrlichia mikurensis was first observed in I. pavlovskyi ticks. Significant inter-species differences in the number of bacterial taxa as well as intra-species diversity related to tick sex were observed. The bacterial communities associated with the I. pavlovskyi ticks displayed a higher biodiversity compared with those of the I. persulcatus and D. reticulatus ticks. Bacterial community structure was also diverse across the studied tick species, as shown by permutational analysis of variance using the Bray-Curtis dissimilarity metric (p = 0.002). Between-sex variation was confirmed by PERMANOVA testing in I. persulcatus (p = 0.042) and I. pavlovskyi (p = 0.042) ticks. Our study indicated that 16S metagenomic profiling could be used for rapid assessment of the occurrence of medically important bacteria in tick populations inhabiting different natural biotopes and therefore the epidemic danger of studied foci. PMID- 26154301 TI - Assessment of clinical occupational dose reduction effect of a new interventional cardiology shield for radial access combined with a scatter reducing drape. AB - OBJECTIVES: To assess the occupational dose reduction effect of a new interventional cardiology shield for radial access combined with a scatter reducing drape. BACKGROUND: Transradial access for catheterization has been shown to increase occupational radiation dose. Current shielding techniques are primarily based on the femoral access. This article looks at the clinical occupational combined dose reduction effect of a commercially available shield and drape which is specific to access type. METHODS: The evaluation took place in a busy interventional cardiology laboratory, with a single plane 30*40 cm flat panel detector (Siemens Artis Zee, Germany). Radiation exposure to staff was measured using electronic personal dosimeters (Unfors RaysafeAB, Sweden) placed at the collar. Patient radiation exposure was assessed using screening time and dose area product per case. Both staff and patient radiation exposure were monitored for a number of case types and operators before, during, and after deployment of the new shield and drapes. RESULTS: The cardiologists' overall median collar badge reading per case reduced from 15.4 MUSv per case without the shield/drape combination to 7.3 MUSv per case with the shield drape combination in situ (P<0.001). The radiographers badge reading was reduced from 4.2 MUSv per case without to 2.5 MUSv per case with the shield drape combination in situ (P<0.001). There was no statistical difference in the cardiac technician's badge reading. Patient's dose area product was not significantly affected by the placement of the shield and drape combination. CONCLUSIONS: The shield/drape combination can significantly reduce operator exposure in a cardiac catheterization laboratory. PMID- 26154303 TI - Prevalence of delirium in geriatric rehabilitation in Israel and its influence on rehabilitation outcomes in patients with hip fractures. AB - The aim of this study was to assess the prevalence of delirium among geriatric patients with hip fractures and to examine the influence of delirium on rehabilitation outcomes. A prospective study was carried out among 95 hip fracture patients admitted to an orthopedic geriatric rehabilitation ward. At admission, the following data were gathered: sociodemographic data, prefracture Activities of Daily Living (ADL), Functional Independence Measure (FIM), Mini Mental State Examination, comorbidities, and medication. Delirium was assessed using the Confusion Assessment Method. The severity of delirium among patients with a positive score on the Confusion Assessment Method was assessed using the Delirium Rating Scale-Revised-98 (DRS-R-98). Rehabilitation outcomes were evaluated by comparing FIM and ADL at admission and at discharge. The research findings showed that the prevalence of delirium among patients was 30%. In addition, a significant difference was found between patients who developed delirium and those who did not. Patients who developed delirium were mostly Jewish, with lower ADL levels at admission, more significant renal failure, lower levels of FIM, and lower Mini-Mental State Examination scores. Furthermore, FIM at discharge and delta FIM were lower among patients who developed delirium than among those who did not. The research conclusions indicated that the functional recovery of patients with delirium is slower. Therefore, it is important to adjust the therapeutic approach to these patients. PMID- 26154302 TI - The Role of Healthcare Professionals in Encouraging Parents to See and Hold Their Stillborn Baby: A Meta-Synthesis of Qualitative Studies. AB - BACKGROUND: Globally, during 2013 there were three million recorded stillbirths. Where clinical guidelines exist some recommend that professionals do not encourage parental contact. The guidance is based on quantitative evidence that seeing and holding the baby is not beneficial for everyone, but has been challenged by bereaved parents' organisations. We aim to inform future guideline development through a synthesis of qualitative studies reporting data relevant to the research question; how does the approach of healthcare professionals to seeing and holding the baby following stillbirth impact parents views and experiences? METHODS/FINDINGS: Using a predetermined search strategy of PubMed and PsychINFO we identified robust qualitative studies reporting bereaved parental views and/or experiences relating to seeing and holding their stillborn baby (final search 24 February, 2014). Eligible studies were English language, reporting parental views, with gestational loss >20 weeks. Quality was independently assessed by three authors using a validated tool. We used meta ethnographic techniques to identify key themes and a line of argument synthesis. We included 12 papers, representing the views of 333 parents (156 mothers, 150 fathers, and 27 couples) from six countries. The final themes were: "[Still]birth: Nature of care is paramount", "Real babies: Perfect beauties, monsters and spectres", and "Opportunity of a lifetime lost." Our line-of argument synthesis highlights the contrast between all parents need to know their baby, with the time around birth being the only time memories can be made, and the variable ability that parents have to articulate their preferences at that time. Thus, we hypothesised that how health professionals approach contact between parents and their stillborn baby demands a degree of active management. An important limitation of this paper is all included studies originated from high income, westernised countries raising questions about the findings transferability to other cultural contexts. We do not offer new evidence to answer the question "Should parents see and hold their stillborn baby?", instead our findings advance understanding of how professionals can support parents to make appropriate decisions in a novel, highly charged and dynamic situation. CONCLUSIONS: Guidelines could be more specific in their recommendations regarding parental contact. The role of healthcare professionals in encouraging parents to see and hold their stillborn baby is paramount. Parental choice not to see their baby, apprehension, or uncertainty should be continuously revisited in the hours after birth as the opportunity for contact is fleeting and final. PMID- 26154304 TI - Identification of proteins involved in desiccation tolerance in the red seaweed Pyropia orbicularis (Rhodophyta, Bangiales). AB - Extreme reduction in cellular water content leads to desiccation, which, if persistent, affects the physiology of organisms, mainly through oxidative stress. Some organisms are highly tolerant to desiccation, including resurrection plants and certain intertidal seaweeds. One such species is Pyropia orbicularis, a rhodophycean that colonizes upper intertidal zones along the Chilean coast. Despite long, daily periods of air exposure due to tides, this alga is highly tolerant to desiccation. The present study examined the proteome of P. orbicularis by 2DE and LC-MS/MS analyses to determine the proteins associated with desiccation tolerance (DT). The results showed that, under natural conditions, there were significant changes in the protein profile during low tide as compared to naturally hydrated plants at high tide. These changes were mainly in newly appeared proteins spots such as chaperones, monodehydroascorbate reductase, and manganese superoxide dismutase, among others. Previously undescribed proteins under desiccation conditions included phycobiliproteins, glyoxalase I, and phosphomannomutase. These changes evidenced that several physiological responses involved in DT are activated during low tide, including decreased photosynthetic activity, increased antioxidant capacity, and the preservation of cell physiology by regulating water content, cell wall structure, and cell volume. Similar responses have been observed in resurrection plants and bryophytes exposed to desiccation. Therefore, the coordinated activation of different desiccation tolerance pathways in P. orbicularis could explain the successful biological performance of this seaweed in the upper intertidal rocky zones. PMID- 26154305 TI - Nanopatterning and Electrical Tuning of MoS2 Layers with a Subnanometer Helium Ion Beam. AB - We report subnanometer modification enabled by an ultrafine helium ion beam. By adjusting ion dose and the beam profile, structural defects were controllably introduced in a few-layer molybdenum disulfide (MoS2) sample and its stoichiometry was modified by preferential sputtering of sulfur at a few nanometer scale. Localized tuning of the resistivity of MoS2 was demonstrated and semiconducting, metallic-like, or insulating material was obtained by irradiation with different doses of He(+). Amorphous MoSx with metallic behavior has been demonstrated for the first time. Fabrication of MoS2 nanostructures with 7 nm dimensions and pristine crystal structure was also achieved. The damage at the edges of these nanostructures was typically confined to within 1 nm. Nanoribbons with widths as small as 1 nm were reproducibly fabricated. This nanoscale modification technique is a generalized approach that can be applied to various two-dimensional (2D) materials to produce a new range of 2D metamaterials. PMID- 26154306 TI - Determining the Provincial and National Burden of Influenza-Associated Severe Acute Respiratory Illness in South Africa Using a Rapid Assessment Methodology. AB - Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the population of South Africa was 50 million and the HIV prevalence was 11%. We used a previously developed methodology to determine severe influenza burden in South Africa. Hospitalized severe acute respiratory illness (SARI) incidence was calculated, stratified by HIV status, for four age groups using data from population-based surveillance in one site situated in Gauteng Province for 2009-2011. These rates were adjusted for each of the remaining 8 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. We estimated non-hospitalized influenza-associated SARI from healthcare utilization surveys at two sites and used the percent of SARI cases positive for influenza from sentinel surveillance to derive the influenza-associated SARI rate. We applied rates of hospitalized and non hospitalized influenza-associated SARI to census data to calculate the national number of cases. The percent of SARI cases that tested positive for influenza ranged from 7-17% depending on age group, year, province and HIV status. In 2010, there were an estimated 21,555 total severe influenza cases in HIV-uninfected individuals and 13,876 in HIV-infected individuals. In 2011, there were an estimated 29,892 total severe influenza cases in HIV-uninfected individuals and 17,289 in HIV-infected individuals. The incidence of influenza-associated SARI was highest in children <5 years and was higher in HIV-infected than HIV uninfected persons in all age groups. Influenza virus was associated with a substantial amount of severe disease, especially in young children and HIV infected populations in South Africa. PMID- 26154307 TI - Range-Wide Genetic Analysis of Little Brown Bat (Myotis lucifugus) Populations: Estimating the Risk of Spread of White-Nose Syndrome. AB - The little brown bat (Myotis lucifugus) is one of the most widespread bat species in North America and is experiencing severe population declines because of an emerging fungal disease, white-nose syndrome (WNS). To manage and conserve this species effectively it is important to understand patterns of gene flow and population connectivity to identify possible barriers to disease transmission. However, little is known about the population genetic structure of little brown bats, and to date, no studies have investigated population structure across their entire range. We examined mitochondrial DNA and nuclear microsatellites in 637 little brown bats (including all currently recognized subspecific lineages) from 29 locations across North America, to assess levels of genetic variation and population differentiation across the range of the species, including areas affected by WNS and those currently unaffected. We identified considerable spatial variation in patterns of female dispersal and significant genetic variation between populations in eastern versus western portions of the range. Overall levels of nuclear genetic differentiation were low, and there is no evidence for any major barriers to gene flow across their range. However, patterns of mtDNA differentiation are highly variable, with high PhiST values between most sample pairs (including between all western samples, between western and eastern samples, and between some eastern samples), while low mitochondrial differentiation was observed within two groups of samples found in central and eastern regions of North America. Furthermore, the Alaskan population was highly differentiated from all others, and western populations were characterized by isolation by distance while eastern populations were not. These data raise the possibility that the current patterns of spread of WNS observed in eastern North America may not apply to the entire range and that there may be broad-scale spatial variation in the risk of WNS transmission and occurrence if the disease continues to spread west. PMID- 26154309 TI - An Exploration Based Cognitive Bias Test for Mice: Effects of Handling Method and Stereotypic Behaviour. AB - Behavioural tests to assess affective states are widely used in human research and have recently been extended to animals. These tests assume that affective state influences cognitive processing, and that animals in a negative affective state interpret ambiguous information as expecting a negative outcome (displaying a negative cognitive bias). Most of these tests however, require long discrimination training. The aim of the study was to validate an exploration based cognitive bias test, using two different handling methods, as previous studies have shown that standard tail handling of mice increases physiological and behavioural measures of anxiety compared to cupped handling. Therefore, we hypothesised that tail handled mice would display a negative cognitive bias. We handled 28 female CD-1 mice for 16 weeks using either tail handling or cupped handling. The mice were then trained in an eight arm radial maze, where two adjacent arms predicted a positive outcome (darkness and food), while the two opposite arms predicted a negative outcome (no food, white noise and light). After six days of training, the mice were also given access to the four previously unavailable intermediate ambiguous arms of the radial maze and tested for cognitive bias. We were unable to validate this test, as mice from both handling groups displayed a similar pattern of exploration. Furthermore, we examined whether maze exploration is affected by the expression of stereotypic behaviour in the home cage. Mice with higher levels of stereotypic behaviour spent more time in positive arms and avoided ambiguous arms, displaying a negative cognitive bias. While this test needs further validation, our results indicate that it may allow the assessment of affective state in mice with minimal training-a major confound in current cognitive bias paradigms. PMID- 26154311 TI - Developmental Herpetology--state of the art of amphibian and reptile developmental biology. PMID- 26154312 TI - A view of amphibian embryology during the last century. AB - Having started working in the field of amphibian embryology over 50 years ago, I make some comments about the changes that seem to me to have taken place in this field over this period. Over the period 1885 to 1960, much of the highly regarded experimental embryology was conducted on amphibian eggs and embryos. Indeed, much of this work was conducted in Germany and Switzerland using eggs and embryos of European newts (salamanders) and frogs of the Rana group. Xenopus started to be used extensively after the 1950s because eggs and embryos could be obtained throughout the year by hormone injection and because sexually mature animals could be raised from an egg within one year. Since the 1960s, publications using Xenopus have exceeded those using other amphibian species by 100-fold. This short commentary highlights some of the major advances attributable to embryological work with Amphibia and exemplifies these advances by reference to those who have made conspicuous contributions in this area. PMID- 26154310 TI - Glial cell line-derived neurotrophic factor in combination with insulin-like growth factor 1 and basic fibroblast growth factor promote in vitro culture of goat spermatogonial stem cells. AB - Growth factors are increasingly considered as important regulators of spermatogonial stem cells (SSCs). This study investigated the effects of various growth factors (GDNF, IGF1, bFGF, EGF and GFRalpha-1) on purification and colonization of undifferentiated goat SSCs under in vitro and in vivo conditions. Irrespective of the culture condition used, the first signs of developing colonies were observed from day 4 of culture onwards. The number of colonies developed in GDNF + IGF1 + bFGF culture condition was significantly higher than the other groups (p < 0.05). In contrast, the size of colonies developed in GDNF + EGF + LIF culture condition was significantly higher than the other groups (p < 0.05). Immunocytochemical stationing for specific biomarkers of somatic cells (vimentin, alpha-inhibin and alpha-SMA) and spermatogonial cells (PLZF, THY 1, VASA, alpha-1 integrin, bet-1 integrin and DBA) revealed that both cell types existed in developing colonies, irrespective of the culture condition used. Even though, the relative abundance of VASA, FGFR3, OCT4, PLZF, BCL6B and THY1 transcription factors in GDNF + IGF1 + bFGF treatment group was significantly higher than the other groups (p < 0.05). Additionally, goat SSCs developed in the latter culture condition could colonize within the seminiferous tubules of the germ-cell depleted recipient mice following xenotransplantation. Obtained results demonstrated that combination of GDNF with IGF1 and bFGF promote in vitro culture of goat SSCs while precludes uncontrolled proliferation of somatic cells. PMID- 26154308 TI - Injections of Algesic Solutions into Muscle Activate the Lateral Reticular Formation: A Nociceptive Relay of the Spinoreticulothalamic Tract. AB - Although musculoskeletal pain disorders are common clinically, the central processing of muscle pain is little understood. The present study reports on central neurons activated by injections of algesic solutions into the gastrocnemius muscle of the rat, and their subsequent localization by c-Fos immunohistochemistry in the spinal cord and brainstem. An injection (300 MUl) of an algesic solution (6% hypertonic saline, pH 4.0 acetate buffer, or 0.05% capsaicin) was made into the gastrocnemius muscle and the distribution of immunolabeled neurons compared to that obtained after control injections of phosphate buffered saline [pH 7.0]. Most labeled neurons in the spinal cord were found in laminae IV-V, VI, VII and X, comparing favorably with other studies, with fewer labeled neurons in laminae I and II. This finding is consistent with the diffuse pain perception due to noxious stimuli to muscles mediated by sensory fibers to deep spinal neurons as compared to more restricted pain localization during noxious stimuli to skin mediated by sensory fibers to superficial laminae. Numerous neurons were immunolabeled in the brainstem, predominantly in the lateral reticular formation (LRF). Labeled neurons were found bilaterally in the caudalmost ventrolateral medulla, where neurons responsive to noxious stimulation of cutaneous and visceral structures lie. Immunolabeled neurons in the LRF continued rostrally and dorsally along the intermediate reticular nucleus in the medulla, including the subnucleus reticularis dorsalis caudally and the parvicellular reticular nucleus more rostrally, and through the pons medial and lateral to the motor trigeminal nucleus, including the subcoerulear network. Immunolabeled neurons, many of them catecholaminergic, were found bilaterally in the nucleus tractus solitarii, the gracile nucleus, the A1 area, the CVLM and RVLM, the superior salivatory nucleus, the nucleus locus coeruleus, the A5 area, and the nucleus raphe magnus in the pons. The external lateral and superior lateral subnuclei of the parabrachial nuclear complex were consistently labeled in experimental data, but they also were labeled in many control cases. The internal lateral subnucleus of the parabrachial complex was labeled moderately. Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently. These data are discussed in terms of an interoceptive, multisynaptic spinoreticulothalamic path, with its large receptive fields and role in the motivational-affective components of pain perceptions. PMID- 26154313 TI - Snakes: hatching of a model system for Evo-Devo? AB - Evo-Devo studies rely on a collection of animal model systems belonging to different phylogenetic branches to try and understand how organisms carrying a similar set of genes and pathways can develop into such a variety of shapes and sizes. The squamate clade, however, has only recently started to receive the attention it deserves in particular due to extreme morphological and metabolic aspects and, consequently, the important insights that it could bring in different fields. The recent sequencing of several squamate genomes as well as the generation of high quality trancriptomes for different snake tissues now provide the necessary tools to complement biological studies. Here, we briefly report on recent work involving developing snake embryos to illustrate their interest to assess vertebrate developmental mechanisms. We also discuss the relevance to use snake species as Evo-Devo model systems and potential ways to cross the important limitations intrinsically associated with developmental and genetic studies of these fascinating animals. PMID- 26154314 TI - Expression of aromatase in the embryonic brain of the olive ridley sea turtle (Lepidochelys olivacea), and the effect of bisphenol-A in sexually differentiated embryos. AB - Brain aromatase participates in several biological processes, such as regulation of the reproductive-endocrine axis, memory, stress, sexual differentiation of the nervous system, male sexual behavior, and brain repair. Here we report the isolation and expression of brain aromatase in olive ridley sea turtle (Lepidochelys olivacea) embryos incubated at male- and female-promoting temperatures (MPT and FPT, respectively), at the thermosensitive period (TSP) and the sex-differentiated period. Also, aromatase expression was assessed in differentiated embryos exposed to bisphenol-A (BPA) during the TSP. BPA is a monomer of polycarbonate plastics and is considered an endocrine-disrupting compound. Normal aromatase expression was measured in both forebrain and hindbrain, showing higher expression levels in the forebrain of differentiated embryos at both incubation temperatures. Although no significant differences were detected in the hindbrain, expression was slightly higher at MPT. BPA did not affect aromatase expression neither in forebrains or hindbrains from embryos incubated at MPT, whereas at FPT an inverted U-shape curve was observed in forebrains with significant differences at lower concentrations, whereas in hindbrains a non-significant increment was observed at higher concentrations. Our data indicate that both incubation temperature and developmental stage are critical factors affecting aromatase expression in the forebrain. Because of the timing and location of aromatase expression in the brain, we suggest that brain aromatase may participate in the imprinting of sexual trends related to reproduction and sexual behavior at the onset of sex differentiation, and BPA exposure may impair aromatase function in the female forebrain. PMID- 26154315 TI - Comparative analysis of pleurodiran and cryptodiran turtle embryos depicts the molecular ground pattern of the turtle carapacial ridge. AB - The turtle shell is a wonderful example of a genuine morphological novelty, since it has no counterpart in any other extant vertebrate lineages. The evolutionary origin of the shell is a question that has fascinated evolutionary biologists for over two centuries and it still remains a mystery. One of the turtle innovations associated with the shell is the carapacial ridge (CR), a bulge that appears at both sides of the dorsal lateral trunk of the turtle embryo and that probably controls the formation of the carapace, the dorsal moiety of the shell. Although from the beginning of this century modern genetic techniques have been applied to resolve the evolutionary developmental origin of the CR, the use of different models with, in principle, dissimilar results has hampered the establishment of a common mechanism for the origin of the shell. Although modern turtles are divided into two major groups, Cryptodira (or hidden-necked turtles) and Pleurodira (or side-necked turtles), molecular developmental studies have been carried out mostly using cryptodiran models. In this study, we revisit the past data obtained from cryptodiran turtles in order to reconcile the different results. We also analyze the histological anatomy and the expression pattern of main CR factors in a pleurodiran turtle, the red-bellied short-necked turtle Emydura subglobosa. We suggest that the turtle shell probably originated concomitantly with the co option of the canonical Wnt signaling pathway into the CR in the last common ancestor of the turtle. PMID- 26154316 TI - zfp36 expression delineates both myeloid cells and cells localized to the fusing neural folds in Xenopus tropicalis. AB - Regulatory RNA binding proteins allow for specific control of gene expression in a very dynamic manner. In mammals ZFP36, formerly known as Tristetraprolin, controls the inflammatory response by binding to an AU-rich element located in the 3' untranslated region of its target mRNAs. The developping embryo relies on a population of primitive macrophages to ensure proper immunity. Although the role of zfp36 in adult immunity has been extensively studied, its expression in the developing immune system has been poorly documented. Here, we have used whole mount in situ hybridization with a 3' UTR specific probe to address the expression of zfp36 in developing Xenopus tropicalis embryos. We have shown that zfp36 is expressed in two distinct cellular populations. First, it is a new marker of primititive myeloid cells, being coexpressed with the myeloid marker mpo. Therefore this early expression may suggest a role for zfp36 in macrophage differentiation and activation. In addition, a second cell population was found to transiently express zfp36, but not mpo, along the fusing neural folds and may correspond to cells undergoing autophagy during neural tube closure. PMID- 26154318 TI - Control of timing of embryonic M-phase entry and exit is differentially sensitive to CDK1 and PP2A balance. AB - Harmonious embryo development requires precise coordination between the timing of the cell cycle and the developmental program. Cyclin accumulation determines the timing of the cell cycle M-phase entry and its degradation determines the timing of the M-phase exit. It is well known that CDK1 and PP2A also govern M-phase entry. However, it is unknown how this kinase and phosphatase regulate the precise timing of events at the beginning of the M-phase and how they cooperate with cyclin metabolism. Here we use Xenopus laevis one-cell embryo cell-free extract experiments to answer this question critical for understanding the regulation of embryo development. Using, separately, low concentrations of the chemical inhibitor of CDK1, RO3306 (RO), or the inhibitor of phosphatases, okadaic acid (OA), we show that moderately diminished CDK1 or PP2A activities results in a delay and an acceleration respectively, of M-phase entry. Simultaneous diminution of CDK1 and PP2A activities results in an intermediate timing of M-phase entry, prolongs the duration of M-phase and diminishes the dynamics of cyclin B2 degradation. We thus show, for the first time, that equilibrium between CDK1 and PP2A specifies the timing of M-phase entry and exit and regulates the dynamics of cyclin B degradation upon M-phase exit in Xenopus laevis first embryonic mitosis. PMID- 26154317 TI - Mechanisms of amphibian macrophage development: characterization of the Xenopus laevis colony-stimulating factor-1 receptor. AB - Macrophage-lineage cells are indispensable to vertebrate homeostasis and immunity. In turn, macrophage development is largely regulated through colony stimulating factor-1 (CSF1) binding to its cognate receptor (CSF1R). To study amphibian monopoiesis, we identified and characterized the X. laevis CSF1R cDNA transcript. Quantitative analysis revealed that CSF1R tissue gene expression increased with X. laevis development, with greatest transcript levels detected in the adult lung, spleen and liver tissues. Notably, considerable levels of CSF1R mRNA were also detected in the regressing tails of metamorphosing animals, suggesting macrophage involvement in this process, and in the adult bone marrow; corroborating the roles for this organ in Xenopus monopoiesis. Following animal infections with the ranavirus Frog Virus 3 (FV3), both tadpole and adult X. laevis exhibited increased kidney CSF1R gene expression. Conversely, while FV3 infected tadpoles increased their spleen and liver CSF1R mRNA levels, the FV3 challenged adults did not. Notably, FV3 induced elevated bone marrow CSF1R expression, and while stimulation of tadpoles with heat-killed E. coli had no transcriptional effects, bacterial stimulation of adult frogs resulted in significantly increased spleen, liver and bone marrow CSF1R expression. We produced the X. laevis CSF1R in recombinant form (rXlCSF1R) and determined, via in vitro cross-linking studies, that two molecules of rXlCSF1R bound the dimeric rXlCSF1. Finally, administration of rXlCSF1R abrogated the rXlCSF1-induced tadpole macrophage recruitment and differentiation as well as bacterial and FV3 elicited peritoneal leukocyte accumulation. This work marks a step towards garnering greater understanding of the unique mechanisms governing amphibian macrophage biology. PMID- 26154319 TI - Epithelial cell division in the Xenopus laevis embryo during gastrulation. AB - How vertebrate epithelial cells divide in vivo and how the cellular environment influences cell division is currently poorly understood. A sine qua non condition to study cell division in situ is the ease of observation of cell division. This is fulfilled in the Xenopus embryo at the gastrula stage where polarized epithelial cells divide with a high frequency at the surface of the organism. Recently, using this model system, we have shown that epithelial cells divide by asymmetric furrowing and that the mode of cell division is regulated during development. Here, we further characterize epithelial cell division in situ. To this end, we used confocal microscopy to study epithelial cell division in the ectoderm of the Xenopus laevis gastrula. Cell division was followed either by indirect immunofluorescence in fixed embryos or by live imaging of embryos transiently expressing diverse fluorescent proteins. Here, we show that during cytokinesis, the plasma membranes of the two daughter cells are usually separated by a gap. For most divisions, daughter cells make contacts basally at a distance from the furrow tip which creates an inverted teardrop-like shaped volume tightly associated with the furrow. At the end of cytokinesis, the inverted teardrop is resorbed; thus it is a transient structure. Several proteins involved in cytokinesis are localized at the tip of the inverted teardrop suggesting that the formation of the gap could be an active process. We also show that intercalation of neighboring cells between daughter cells occasionally occurs during cytokinesis. Our results reveal an additional level of complexity in the relationship between dividing cells and also with their neighboring cells during cytokinesis in the Xenopus embryo epithelium. PMID- 26154320 TI - Activin ligands are required for the re-activation of Smad2 signalling after neurulation and vascular development in Xenopus tropicalis. AB - The importance of Transforming Growth Factor beta (TGFbeta) signalling during early development has been well established. In particular, Nodal ligands have been shown to play essential roles for the specification and the patterning of the mesendoderm, axes formation and organogenesis. Activin ligands, like Nodal, signal by inducing the phosphorylation of the intracellular signal transducers Smad2 and Smad3. However, the roles of Activins during embryonic development are much less understood. Here, we report that during Xenopus tropicalis development two waves of Smad2 phoshorylation can be observed, first during gastrulation and then a second one after neurulation. Using a knock-down approach, we show that the second wave of Smad2 phosphorylation depends on activinbetaa (actbetaa) and activinbetab (actbetab) expression. Knocking down the expression of actbetaa, or treating the embryos with a chemical inhibitor inhibiting TGFbeta receptor I (TGFbetaRI) activity after neurulation result in a decrease of the expression of endothelial cell markers and a lack of blood flow in Xenopus tadpoles. Taken together these data suggest that Activin ligands play an important role during vascular development in Xenopus tropicalis embryos. PMID- 26154321 TI - Intracellular localizations of the Dead End protein in Xenopus primordial germ cells. AB - We investigated the intracellular localization of Xenopus Dead end protein (Dnd1) in primordial germ cells during early development by expressing the tagged protein in transgenic Xenopus embryos, with the germ plasm visualized. Dnd1 initially localized to the germ plasm in the cortex, moved to the perinuclear region together with the germ plasm after the midblastula transition, and then entered the nucleus. Using Dnd1 deletion mutants, we identified two distinct but overlapping regions of Dnd1 that were responsible for localization to either the germ plasm or nucleus. These Dnd1 regions appeared to function in primordial germ cell- and stage-specific manners. PMID- 26154322 TI - Activation of spleen tyrosine kinase (Syk) at fertilization in Rhinella arenarum eggs. AB - Recently, we have provided evidence for the involvement of a cytosolic tyrosine phosphorylatable 70 kDa oocyte protein in Rhinella arenarum (Anura: Bufonidae) fertilization. The aim of the present work was to characterize its phosphorylation, determine the identity of this protein and establish its biological role during the fertilization process. Tyrosine phosphorylation of the 70 kDa protein was not observed in eggs activated with the calcium ionophore A23187. Pretreatment of oocytes with the tyrosine kinase inhibitor genistein effectively blocked the fertilization-dependent phosphorylation of the 70 kDa protein. In order to identify this protein, we examined the presence in amphibian oocytes of non-receptor 70 kDa tyrosine kinase members of the Syk/Zap70 and Tec families by RT-PCR using degenerate primers. We found that R. arenarum oocytes contain the transcripts coding for Syk and Tec kinases. Western blot analysis confirmed the presence of Syk protein in unfertilized oocytes and eggs. Studies using phospho-Syk specific antibodies showed that fertilization rapidly (less than 10 minutes) induces phosphorylation on Syk tyrosine residues (352 and 525/526) that are necessary for the activation of the enzyme. Finally, specific inhibition of Syk with the R406 compound provoked a diminished fertilization score, thereby confirming a functional role of the Syk protein during R. arenarum fertilization. To our knowledge this is the first time that Syk is described as a player in the signaling cascade activated after fertilization. PMID- 26154323 TI - Bidder's organ--structure, development and function. AB - Bidder's organ is an ovary-like structure, which develops from the anterior part of the gonadal ridge in anuran amphibians belonging to the Bufonidae family. Bidder's organs form in both males and females. Because Bidder's organ contains female germ cells (oocytes), the bufonid males are de facto hermaphrodites. Due to similarity with the undeveloped ovary, Bidder's organ was, in early literature, described, inaccurately, as a structure present only in males. Due to the fact that Bidder's organ is a unique structure present only in Bufonidae, it is not well studied and its function still remains a mystery. Here we describe the development and structure of Bidder's organs, summarize the knowledge on gene expression and steroidogenic activity in these organs, and present hypotheses regarding Bidder's organ function. PMID- 26154324 TI - Transition from embryonic to adult epidermis in reptiles occurs by the production of corneous beta-proteins. AB - The adaptation of the epidermis in amniote vertebrates to life on land took place by a drastic change from an embryonic epidermis made of two-four periderm layers to a terrestrial-proof epidermis. This transition occurred by the increase in types and number of specialized corneous proteins coded by genes of the Epidermal Differentiation Complex. The prevalent types of corneous proteins produced in the reptilian epidermis contain a beta-sheet region of high amino acid homology which allows their polymerization into a meshwork of filaments forming the hard corneous material of scales and claws. The present immunogold ultrastructural study shows that this transition occurs with the synthesis of glycine-rich corneous beta-proteins (formerly indicated as beta-keratins) that are added to the initial framework of acidic intermediate filaments produced in the embryonic epidermis of lizards, snake, alligator and turtle. These corneous beta-proteins are accumulated in the transitional and definitive layers of reptilian epidermis formed underneath the transitory two-four layered embryonic epidermis. In the more specialized reptiles capable of shedding the epidermis as a single unit, such as lizards and snakes, special glycine-cysteine rich beta-proteins are initially produced in a single layer immediately formed beneath the embryonic epidermis, the oberhautchen. The latter layer allows the in ovo shedding of the embryonic epidermis in preparation for hatching, and in the following shedding cycles of the adult epidermis. The production of specialized corneous-specific beta-proteins in addition to intermediate filament keratins was probably an essential addition for terrestrial life during the evolution of reptiles into different lineages, including birds. The increase of glycine and cysteine in epidermal proteins enhanced the hydrophobicity, insolubility and mechanical strength of the stratum corneum in these amniotes. PMID- 26154325 TI - Comparative expression analysis of cysteine-rich intestinal protein family members crip1, 2 and 3 during Xenopus laevis embryogenesis. AB - Members of the cysteine-rich intestinal protein (Crip) family belong to the group 2 LIM proteins. Crip proteins are widely expressed in adult mammals but their expression profile and function during embryonic development are still mostly unknown. In this study, we have described for the first time the spatio-temporal expression pattern of the three family members crip1, crip2 and crip3 during Xenopus laevis embryogenesis by RT-PCR and whole mount in situ hybridization approaches. We observed that all three genes are expressed in the pronephros, branchial arches and the eye. Furthermore, crip1 transcripts could be visualized in the developing cranial ganglia and neural tube. In contrast, crip2 could be detected in the cardiovascular system, the brain and the neural tube while crip3 was expressed in the cranial ganglions and the heart. Based on these findings, we suggest that each crip family member may play an important role during embryonic development. PMID- 26154326 TI - Reptile genomes open the frontier for comparative analysis of amniote development and regeneration. AB - Developmental genetic studies of vertebrates have focused primarily on zebrafish, frog and mouse models, which have clear application to medicine and well developed genomic resources. In contrast, reptiles represent the most diverse amniote group, but have only recently begun to gather the attention of genome sequencing efforts. Extant reptilian groups last shared a common ancestor ?280 million years ago and include lepidosaurs, turtles and crocodilians. This phylogenetic diversity is reflected in great morphological and behavioral diversity capturing the attention of biologists interested in mechanisms regulating developmental processes such as somitogenesis and spinal patterning, regeneration, the evolution of "snake-like" morphology, the formation of the unique turtle shell, and the convergent evolution of the four-chambered heart shared by mammals and archosaurs. The complete genome of the first non-avian reptile, the green anole lizard, was published in 2011 and has provided insights into the origin and evolution of amniotes. Since then, the genomes of multiple snakes, turtles, and crocodilians have also been completed. Here we will review the current diversity of available reptile genomes, with an emphasis on their evolutionary relationships, and will highlight how these genomes have and will continue to facilitate research in developmental and regenerative biology. PMID- 26154327 TI - In silico identification of the genes for sperm-egg interaction in the internal fertilization of the newt Cynops pyrrhogaster. AB - A specific sperm-egg interaction in the oviductal matrix is crucial for internal fertilization of the red-bellied newt, Cynops pyrrhogaster. An understanding of the molecular basis of this interaction is expected to elucidate the evolutionary history of internal fertilization in amphibians. Recently, deep sequencing technology has provided global gene information even in nonmodel animals, allowing us to understand specific features of the molecular mechanisms underlying fertilization in C. pyrrhogaster. In the present study, we screened de novo assembled RNAseq from ovary, testis, and oviduct samples in C. pyrrhogaster and identified the base sequences encoding zona pellucida (ZP) proteins, voltage dependent Ca(2+) channels, and cysteine-rich secretory proteins (CRISPs), which respectively are sperm receptors for egg envelopes, major mediators of sperm intracellular signaling, and expected extracellular modulators for sperm function in the female reproductive tract. In the ovary, ZP homologues of all six subgroups were found, including a ZP1 homologue that was newly found in amphibians, a ZP4 homologue, and six ZPC homologues. The unique combination of ZP proteins suggests a new mechanism for sperm binding to egg envelopes in the internal fertilization of C. pyrrhogaster. In the testis, CaV1.1, 1.2, and 3.2, which are L- and T-type voltage-dependent Ca(2+) channels, were found as potential mediators for the internal fertilization-specific sperm-egg interaction. We also found CRISP 2 in the oviduct, which is speculated to participate in the sperm-egg interaction. These results indicate that the de novo assembled RNAseq is a powerful tool allowing analysis of the specific sperm-egg interactions in C. pyrrhogaster. PMID- 26154328 TI - The genome sequence of the corn snake (Pantherophis guttatus), a valuable resource for EvoDevo studies in squamates. AB - Squamates (snakes and lizards) exhibit a striking variety of phenotypes, with little known on their generative mechanisms. Studies aiming to understand the genetic basis of this wide diversity in morphology, physiology and ecology will greatly benefit from whole genome sequencing initiatives, as they provide the foundation for comparative analyses and improve our understanding of the evolution, development and diversification of traits. Here, we present the first draft genome of the corn snake Pantherophis guttatus, an oviparous snake that we promote as a particularly appropriate model species for evolutionary developmental studies in squamates. We sequenced 100-base paired-end reads from multiple individuals of a single family (parents and offspring) that produced a genome assembly of 1.53 gigabases (Gb), roughly covering 75% of the expected total genome size, and 297,768 scaffolds >1 Kb. We were able to fully retrieve 86, and partially another 106, of the 248 CEGMA core genes, indicating that a high genome completeness was achieved, even though the assembly is fragmented. Using MAKER2, we annotated 10,917 genes with high confidence (Annotation Edit Distance (AED)<1) and an additional 5,263 predicted genes matched with the species' transcriptome. Numerous colour and colour pattern morphs exist in P. guttatus, making it an ideal model to study the genetic determinism, development, and evolution of adaptive colour traits in reptiles. Using our draft genome and a Single-Nucleotide Polymorphism (SNP) calling approach, we confirmed the interval with the causative mutation for the amelanistic phenotype, a result supported by a parallel exome-based study. PMID- 26154329 TI - Amniote yolk sacs: diversity in reptiles and a hypothesis on their origin. AB - Oviparous amniotes produce a large yolky egg that gives rise to a free-living hatchling. Structural characteristics and functional attributes of the egg are best known for birds, which have a large mass of fluid yolk surrounded by an extraembryonic yolk sac. Yolk nutrients are delivered to the embryo via the vascular yolk sac. This developmental pattern and nutrient transport mechanism is thought to be representative of all other lineages of amniotes. Recent discovery of a snake with cellularized yolk organized around a meshwork of blood vessels reveals an additional pattern for yolk mobilization, which may also occur in other squamate reptiles (lizards and snakes). This complex yolk sac raises interesting questions about developmental mechanisms and suggests a possible model for the transition between the egg of anamniotes and that of amniotes. PMID- 26154330 TI - Digit evolution in gymnophthalmid lizards. AB - The tetrapod limb is a highly diverse structure, and reduction or loss of this structure accounts for many of the limb phenotypes observed within species. Squamate reptiles are one of the many tetrapod lineages in which the limbs have been greatly modified from the pentadactyl generalized pattern, including different degrees of reduction in the number of limb elements to complete limblessness. Even though limb reduction is widespread, the evolutionary and developmental mechanisms involved in the formation of reduced limb morphologies remains unclear. In this study, we present an overview of limb morphology within the microteiid lizard group Gymnophthalmidae, focusing on digit arrangement. We show that there are two major groups of limb-reduced gymnophthalmids. The first group is formed by lizard-like (and frequently pentadactyl) species, in which minor reductions (such as the loss of 1-2 phalanges mainly in digits I and V) are the rule; these morphologies generally correspond to those seen in other squamates. The second group is formed by species showing more drastic losses, which can include the absence of an externally distinct limb in adults. We also present the expression patterns of Sonic Hedgehog (Shh) in the greatly reduced fore and hindlimb of a serpentiform gymnophthalmid. Our discussion focuses on identifying shared patterns of limb reduction among tetrapods, and explaining these patterns and the morphological variation within the gymnophthalmids based on current knowledge of the molecular signaling pathways that coordinate limb development. PMID- 26154331 TI - Evolution of maternal egg size effects in sister salamander species. AB - Egg size varies genetically and with the maternal environment. It is correlated with and can act as a resource fueling variation in many other key life history traits. This study examined hypotheses about how plastic responses of offspring to yolk variation evolve (and contribute to phenotypic evolution) when maternal investment in egg size evolves. I used a split-clutch, controlled, surgical experiment with a longitudinal (repeated-measures) design to examine the effects of yolk removal on sister salamander species with distinct egg and larval phenotypes. Yolk removal had large effects in the derived larger-egged species, A. barbouri, and greatly reduced effects in A. texanum. Early hatching and smaller larval body size was only found in A. barbouri and survival rates decreased more in A. barbouri. These results provide strong experimental evidence that as female salamanders evolve greater yolk investment in each egg, offspring coevolve an increased magnitude of phenotypic plasticity in response to yolk variation across a suite of life history traits. Yolk therefore acts as an integrator of phenotypes that allows females to modify modules of life history traits together (facilitating adaptation). When organisms invade new environments, complex integrated phenotypes may evolve via correlated responses to increased maternal investment, yet individual traits can be coupled or decoupled to yolk quantity variation in different species. PMID- 26154332 TI - The importance of cartilage to amphibian development and evolution. AB - The duality of amphibians is epitomized by their pharyngeal arch skeletons, the larval and adult morphologies of which enable very different feeding and breathing behaviors in aquatic and terrestrial life. To accomplish this duality, amphibian pharyngeal arch skeletons undergo two periods of patterning: embryogenesis and metamorphosis, and two periods of growth: larval and postmetamorphic. Their extreme ontogenetic variation, however, is coupled with relatively limited phylogenetic variation. I propose that amphibians face an evolutionary tradeoff between their ontogenetic and phylogenetic diversification that stems from the need to grow and transform the pharyngeal arch skeleton in cartilage rather than bone. Cartilage differs fundamentally from bone in its histology, function, development and growth. Cartilage is also the first skeletal tissue to form embryonically and provides more cellular pathways for shape change than bone. This article combines morphological, histological and experimental perspectives to explore how pharyngeal arch cartilage shape is controlled in amphibian embryogenesis, growth and metamorphosis, and how amphibian skeletal ontogenies are impacted by using cartilage to evolve a complex life cycle and in evolving away from a complex life cycle. PMID- 26154333 TI - Evolutionary trend for metamery reduction and gonad shortening in Anurans revealed by comparison of gonad development. AB - The gonads develop as the metameric mesodermal structures at the ventral surface of the mesonephroi. To study the evolutionary trends for anuran gonads, we performed comparative analysis of three species from the basal paraphyletic group - Archaeobatrachia (Bombina bombina, Xenopus laevis, Pelobates fuscus) and five species from more derived monophyletic Neobatrachia group (Hyla arborea, Bufotes viridis, Rana dalmatina, Rana arvalis, Rana temporaria). Light and scanning electron microscopy analysis showed that in Archaeobtrachia the undifferentiated gonads and ovaries, but not the testes, have pronounced external metamery. In contrast, Neobatrachia lacked external gonadal metamery and the internal metamery was well pronounced in the ovaries, but only rudimentary in the testes. There was also a difference in the site of genital ridge formation between these two groups. In Archaeobatrachia, the genital ridges developed along almost the entire length of mesonephroi, while in Neobatrachia they were limited to the anterior parts of the mesonephroi. A transient form was observed in P. fuscus, where the gonads formed along the anterior half of the mesonephroi. There was also an evolutionary trend for gradual postero-anterior shortening of the gonadal anlagen. In summary, our study indicates that among anurans there is an evolutionary trend for the gradual loss of metamery and shortening of the gonad. PMID- 26154334 TI - Evolution of viviparous reproduction in Paleozoic and Mesozoic reptiles. AB - Although viviparity (live-bearing reproduction) is widely distributed among lizards and snakes, it is entirely absent from other extant Reptilia and many extinct forms. However, paleontological evidence reveals that viviparity was present in at least nine nominal groups of pre-Cenozoic reptiles, representing a minimum of six separate evolutionary origins of this reproductive mode. Two viviparous clades (sauropterygians and ichthyopterygians) lasted more than 155 million years, a figure that rivals the duration of mammalian viviparity. Circumstantial evidence indicates that extinct viviparous reptiles had internal fertilization, amniotic fetal membranes, and placentas that sustained developing embryos via provision of respiratory gases, water, calcium, and possibly organic nutrients. Production of offspring via viviparity facilitated the invasion of marine habitats in at least five reptilian lineages. Thus, this pattern of embryonic development and reproduction was central to the ecology and evolution of these ancient animals, much as it is to numerous extant species of vertebrates. PMID- 26154335 TI - Integrating developmental biology and the fossil record of reptiles. AB - Numerous new discoveries and new research techniques have influenced our understanding of reptile development from a palaeontological perspective. They suggest for example that transition from mineralized to leathery eggshells and from oviparity to viviparity appeared much more often in the evolution of reptiles than was previously thought. Most marine reptiles evolved from viviparous terrestrial ancestors and had probably genetic sex determination. Fossil forms often display developmental traits absent or rare among modern ones such as polydactyly, hyperphalangy, the presence of ribcage armour, reduction of head ornamentation during ontogeny, extreme modifications of vertebral count or a wide range of feather-like structures. Thus, they provide an empirical background for many morphogenetic considerations. PMID- 26154336 TI - Comparison of Consumer and Research Monitors under Semistructured Settings. AB - PURPOSE: This study evaluated the relative validity of different consumer and research activity monitors during semistructured periods of sedentary activity, aerobic exercise, and resistance exercise. METHODS: Fifty-two (28 male and 24 female) participants age 18-65 yr performed 20 min of self-selected sedentary activity, 25 min of aerobic exercise, and 25 min of resistance exercise, with 5 min of rest between each activity. Each participant wore five wrist-worn consumer monitors [Fitbit Flex, Jawbone Up24, Misfit Shine (MS), Nike+ Fuelband SE (NFS), and Polar Loop] and two research monitors [ActiGraph GT3X+ on the waist and BodyMedia Core (BMC) on the arm] while being concurrently monitored with Oxycon Mobile (OM), a portable metabolic measuring system. Energy expenditure (EE) on different activity sessions was measured by OM and estimated by all monitors. RESULTS: Mean absolute percent error (MAPE) values for the full 80-min protocol ranged from 15.3% (BMC) to 30.4% (MS). EE estimates from ActiGraph GT3X+ were found to be equivalent to those from OM (+/- 10% equivalence zone, 285.1-348.5). Correlations between OM and the various monitors were generally high (ranged between 0.71 and 0.90). Three monitors had MAPE values lower than 20% for sedentary activity: BMC (15.7%), MS (18.2%), and NFS (20.0%). Two monitors had MAPE values lower than 20% for aerobic exercise: BMC (17.2%) and NFS (18.5%). None of the monitors had MAPE values lower than 25% for resistance exercise. CONCLUSION: Overall, the research monitors and Fitbit Flex, Jawbone Up24, and NFS provided reasonably accurate total EE estimates at the individual level. However, larger error was evident for individual activities, especially resistance exercise. Further research is needed to examine these monitors across various activities and intensities as well as under real-world conditions. PMID- 26154337 TI - Comparing Simple Insulin Sensitivity Indices to the Oral Minimal Model Postexercise. AB - PURPOSE: This study aims to establish whether changes in indices of insulin sensitivity (Si) derived from fasting glucose and an oral glucose tolerance test (OGTT) are comparable to Si determined by the oral minimal model (OMM) in response to acute moderate-intensity exercise (MIE) and high-intensity exercise (HIE). METHODS: Eighteen prediabetic subjects completed three conditions: control (no exercise), ~ 200 kcal of MIE (~ 50% of VO2peak), and ~ 200 kcal of HIE (~ 80% VO2peak). One hour postexercise (or control), subjects underwent a 75-g OGTT; plasma glucose and insulin were measured to determine Si using several OGTT-based indices (OMM, Belfiore index, Cederholm index, Matsuda index, Gutt index, oral glucose insulin sensitivity index, Stumvoll metabolic clearance rate, Stumvoll insulin sensitivity index, 1/mean OGTT insulin, and 1/insulin incremental area under the curve) and fasting indices (1/homeostatic model assessment for insulin resistance, 1/adipose tissue insulin resistance, 40/fasting insulin, and Quantitative Insulin Sensitivity Check Index). ANOVA and Pearson's correlations were used to examine relationships between changes in Si (DeltaSi) among various indices compared to the OMM. RESULTS: Exercise resulted in a significant increase in Si, according to OGTT-based indices ranging from 11% to 51% (MIE, P < 0.04) and from 8% to 85% (HIE, P < 0.05). Fasting indices showed no change in response to MIE (P > 0.29) and a decrease in Si following HIE (P < 0.001). OGTT-based and fasting indices underpredicted DeltaSi-OMM by ~ 40% and ~ 90% following MIE and HIE, respectively. DeltaSi-OMM following MIE was moderately correlated with DeltaSi estimated by OGTT-based indices, but not fasting indices. In contrast, DeltaSi-OMM following HIE was not significantly correlated with any Si index. CONCLUSIONS: Insulin sensitivity increases postexercise, according to most Si models. However, there is high variability between indices under each condition, and these measures only correlate with the OMM following MIE. Caution should be exerted when drawing conclusions about the insulin-sensitizing effects of exercise based on OGTT and fasting indices. PMID- 26154338 TI - A Randomized Trial on Home Telemonitoring for the Management of Metabolic and Cardiovascular Risk in Patients with Type 2 Diabetes. AB - BACKGROUND: This study evaluated whether a home telehealth (HT) system enabling the patient to monitor body weight, blood glucose values, and blood pressure values, associated with remote educational support and feedback to the general practitioner, can improve metabolic control and overall cardiovascular risk in individuals with type 2 diabetes mellitus, compared with usual practice. MATERIALS AND METHODS: This was a randomized, parallel-group (1:1), open-label, multicenter study conducted in general practice. Follow-up was for 12 months. RESULTS: Overall, 29 general practitioners enrolled 302 patients (153 assigned to the HT group and 149 to the control group). Use of the HT system was associated with a statistically significant reduction in glycated hemoglobin (HbA1c) levels compared with the control group (estimated mean difference, 0.33+/-0.1; P=0.001). No difference emerged as for body weight, blood pressure, and lipid profile. The proportion of patients reaching the target of HbA1c <7.0% was higher in the HT group than in the control group after 6 months (33.0% vs. 18.7%; P=0.009) and 12 months (28.1% vs. 18.5%; P=0.07). As for quality of life (evaluated with the 36 item Short Form health survey), significant differences in favor of the HT group were detected as for physical functioning (P=0.01), role limitations due to emotional problems (P=0.02), mental health (P=0.005), and mental component summary (P=0.03) scores. A lower number of specialist visits was reported in the telemedicine group (incidence rate ratio, 0.72; 95% confidence interval, 0.51 1.01; P=0.06). CONCLUSIONS: Use of the HT system was associated with better metabolic control and quality of life; a marginally nonsignificant lower resource utilization was also documented. No impact was documented on blood pressure, lipid profile, and body weight. PMID- 26154339 TI - Correction: An Integrative Approach for Modeling and Simulation of Heterocyst Pattern Formation in Cyanobacteria Filaments. PMID- 26154340 TI - Adherence to Teledermatology Recommendations by Primary Health Care Professionals: Strategies for Improving Follow-up on Teledermatology Recommendations. PMID- 26154341 TI - Interaction of synchronized dynamics in cortex and basal ganglia in Parkinson's disease. AB - Parkinson's disease pathophysiology is marked by increased oscillatory and synchronous activity in the beta frequency band in cortical and basal ganglia circuits. This study explores the functional connections between synchronized dynamics of cortical areas and synchronized dynamics of subcortical areas in Parkinson's disease. We simultaneously recorded neuronal units (spikes) and local field potentials (LFP) from subthalamic nucleus (STN) and electroencephalograms (EEGs) from the scalp in parkinsonian patients, and analysed the correlation between the time courses of the spike-LFP synchronization and inter-electrode EEG synchronization. We found the (non-invasively obtained) time course of the synchrony strength between EEG electrodes and the (invasively obtained) time course of the synchrony between spiking units and LFP in STN to be weakly, but significantly, correlated with each other. This correlation is largest for the bilateral motor EEG synchronization, followed by bilateral frontal EEG synchronization. Our observations suggest that there may be multiple functional modes by which the cortical and basal ganglia circuits interact with each other in Parkinson's disease: not only may synchronization be observed between some areas in cortex and the basal ganglia, but also synchronization within cortex and within basal ganglia may be related, suggesting potentially a more global functional interaction. More coherent dynamics in one brain region may modulate or activate the dynamics of another brain region in a more powerful way, causing correlations between changes in synchrony strength in the two regions. PMID- 26154345 TI - Muscle strength and hypertrophy occur independently of protein supplementation during short-term resistance training in untrained men. AB - Short-term resistance training has consistently demonstrated gains in muscular strength, but not hypertrophy. Post-resistance training protein ingestion is posited to augment the acute anabolic stimulus, thus potentially accelerating changes in muscle size and strength. The purpose of this investigation was to examine the effects of 4 weeks of resistance training with protein supplementation on strength and muscle morphology changes in untrained men. Participants (mean +/- SD; N = 18; age, 22.0 +/- 2.5 years; body mass index, 25.1 +/- 5.4 kg . m(-2)) were randomly assigned to a resistance training + protein group (n = 9; whey (17 g) + colostrum (3 g) + leucine (2 g)) or a resistance training + placebo group (n = 9). One-repetition maximum (1RM) strength in the leg press (LP) and leg extension (LE) exercises, maximal isometric knee extensor strength (MVIC), and muscle morphology (thickness (MT), cross-sectional area (CSA), pennation angle) of the dominant rectus femoris (RF) and vastus lateralis (VL) was assessed before and after training. Participants performed LP and LE exercises (3 * 8-10; at 80% 1RM) 3 days/week for 4 weeks. Data were analyzed using 2-way ANOVA with repeated measures. Four weeks of resistance training resulted in significant increases in LP (p < 0.001), LE (p < 0.001), MVIC (p < 0.001), RF MT (p < 0.001), RF CSA (p < 0.001), VL MT (p < 0.001), and VL CSA (p < 0.001). No between-group differences were observed. Although nutrition can significantly affect training adaptations, these results suggest that short-term resistance training augments muscle strength and size in previously untrained men with no additive benefit from postexercise protein supplementation. PMID- 26154344 TI - Analysis of provider specialties in the treatment of patients with clinically diagnosed back and joint problems. AB - RATIONALE, AIMS AND OBJECTIVES: Although several studies have compared patient outcomes by provider specialty in the treatment of back and joint pain, little is known about the cost-effectiveness of improving patient outcomes across specialties. This study uses a large-scale, nationally representative database to evaluate the cost-effectiveness of being treated by specific provider specialists for back and joint pain in the United States. METHOD: The 2002-2012 Medical Expenditure Panel Surveys were used to examine patients diagnosed with back and/or joint problems seeking treatment from doctors (internal medicine, family/general, osteopathic medicine, orthopaedics, rheumatology, neurology) or other providers (chiropractor, physical therapist, acupuncturist, massage therapist). A total of 16,546 respondents aged 18 to 85 and clinically diagnosed with back/joint pain were examined. Self-reported measures of physical and mental health and general quality of life (measured by the EuroQol-5D) were compared with average total costs of treatment across medical providers. RESULTS: Total annual treatment costs per person ranged from $397 for family/general doctors to $1205 for rheumatologists. Cost-effectiveness analysis suggests that osteopathic, family/general, internal medicine doctors and chiropractors and massage therapists were more cost-effective than other specialties in improving physical function to back pain patients. For mental health measures, family/general and orthopaedic doctors and physical therapists were more cost-effective compared with other specialties. Similar to results on physical function, family/general, osteopathic and internal medicine doctors dominated other specialties. However, only massage therapy was cost-effective among non-doctor providers in improving quality of life measures. CONCLUSIONS: Patients seeking care for back and joint related health problems face a wide range of treatments, costs and outcomes depending on which specialist provider they see. This study provides important insight on the relationship between health care costs and patients' perceived physical and mental health status from receiving treatment for diagnosed back/joint problems. PMID- 26154343 TI - Risk Factors of Coronary Artery Disease in Secondary Prevention--Results from the AtheroGene--Study. AB - BACKGROUND: Risk factors are important in cardiovascular (CV) medicine for risk stratification of patients. We aimed to compare the traditional risk factors to clinical variables for the prediction of secondary cardiovascular events. METHODS AND RESULTS: For this study, 3229 patients with known coronary artery disease (CAD) were included. We calculated whether the traditional risk factors, diabetes mellitus, increased LDL/HDL ratio, arterial hypertension and smoking alone and in combination with the clinical variables, ejection fraction, creatinine clearance, multi-vessel disease and CRP concentration predict the outcome cardiovascular death or non-fatal myocardial infarction (N = 432) during the mean follow-up time of 4.2 +/- 2.0 years. In this cohort diabetes mellitus was the risk factor with the strongest influence regarding occurrence of secondary events (hazard ratio; HR:1.70, confidence interval; CI 95%: 1.36-2.11; P<0.0001), followed by LDL/HDL ratio and smoking. However, risk stratification is further improved by using additional clinical variables like ejection fraction (HR:3.30 CI 95%:2.51-4.33; P>0.0001) or calculated creatinine clearence (Cockroft-Gault formula) (HR:2.26 CI 95%:1.78-2.89; P<0.0001). Further ameliorating risk stratification from the clinical variables were CRP and multi-vessel disease. The most precise risk prediction was achieved when all clinical variables were added to the CV risk factors. CONCLUSION: Diabetes mellitus has the strongest influence to predict secondary cardiovascular events in patients with known CAD. Risk stratification can further be improved by adding CV risk factors and clinical variables together. Control of risk factors is of paramount importance in patients with known CAD, while clinical variables can further enhance prediction of events. PMID- 26154346 TI - An Observational Study of Honey Bee Colony Winter Losses and Their Association with Varroa destructor, Neonicotinoids and Other Risk Factors. AB - This article presents results of an analysis of honey bee losses over the winter of 2011-2012 in the Netherlands, from a sample of 86 colonies, located at 43 apiaries. The apiaries were selected using spatially stratified random sampling. Colony winter loss data were collected and related to various measures of colony strength recorded in summer, as well as data from laboratory analysis of sample material taken from two selected colonies in each of the 43 apiaries. The logistic regression model which best explained the risk of winter loss included, in order of statistical importance, the variables (1) Varroa destructor mite infestation rate in October 2011, (2) presence of the cyano-substituted neonicotinoids acetamiprid or thiacloprid in the first 2 weeks of August 2011 in at least one of the honey bee matrices honey, bees or bee bread (pollen), (3) presence of Brassica napus (oilseed rape) or Sinapis arvensis (wild mustard) pollen in bee bread in early August 2011, and (4) a measure of the unexplained winter losses for the postal code area where the colonies were located, obtained from a different dataset. We consider in the discussion that reduced opportunities for foraging in July and August because of bad weather may have added substantially to the adverse effects of acetamiprid and thiacloprid. A novel feature of this work is its use of postal code random effects from two other independent datasets collected in the annual national monitoring by questionnaires of winter losses of honey bees in the Netherlands. These were used to plan the sample selection and also in the model fitting of the data in this study. It should however be noted that the results of the present pilot study are based on limited data, which may consequently reveal strong factors but fail to demonstrate possible interaction effects. PMID- 26154347 TI - Electrocatalytic Nitrate Reduction by a Cobalt Protoporphyrin Immobilized on a Pyrolytic Graphite Electrode. AB - A series of simple molecular catalysts, i.e., Co(III), Fe(II), Ni(II), Cu(II), and Rh(II) protoporphyrins (metal-PP), directly adsorbed on pyrolytic graphite have been utilized for catalyzing the electrochemical reduction of nitrate. These catalysts are studied by combining cyclic voltammetry with online electrochemical mass spectrometry (OLEMS) to monitor volatile products and online ion chromatography (IC) to detect ionic products in the aqueous electrolyte solution. Among all investigated porphyrins, the Co-based protoporphyrin shows the highest selectivity toward hydroxylamine (NH2OH), which made it the catalyst of primary interest in the article. The reactivity and selectivity of the immobilized Co protoporphyrin depend significantly on pH, with more acidic conditions leading to higher reactivity and higher selectivity toward hydroxylamine over ammonia. Potential controlled electrolysis results show that the potential also greatly influences the selectivity: at pH 1, hydroxylamine is the main product around 0.5 V with approximately 100% selectivity, while hydroxylamine and ammonia are both formed at a more negative potential, -0.75 V. The mechanism of the reaction is discussed, invoking of the possibility of two pathways for hydroxylamine/ammonia formation: a sequential pathway in which hydroxylamine is produced as an intermediate, with ammonia subsequently formed through the reduction of NH2OH/NH3OH(+), and a parallel pathway in which the formation of hydroxylamine and ammonia is derived from a common intermediate. PMID- 26154348 TI - Surgical Correction and Outcome of Exotropia. PMID- 26154349 TI - Identification of Intraorbital Arteries in Pediatric Age by High Resolution Superselective Angiography. AB - PURPOSE: Angiography is a powerful tool to identify intraorbital arteries. However, the incidence by which these vessels can be identified is unknown. Our purpose was to determine such incidence and which angiographic approach is best for the identification of each artery. METHODS: A retrospective study of 353 angiographic procedures (via ophthalmic artery and/or external carotid artery) carried out on 79 children affected by intraocular retinoblastoma was made to investigate the arterial anatomy in 87 orbits. For each intraorbital artery two parameters were calculated: the angiographic incidence, as the percentage of times a given artery was identified, and the visibility index, as the ratio between the angiographic incidence and the true anatomic incidence. RESULTS: All collaterals of the ophthalmic artery could be spotted. Most of them were identified with a high angiographic incidence; some of them were less easily identified because too thin or because frequently shielded. The visibility index paralleled the angiographic incidence of most arteries. However, the lacrimal and meningolacrimal arteries had a higher visibility index suggesting that their identification was more frequent than the angiographic incidence alone could suggest. Statistical analysis demonstrated that the lacrimal artery and some muscular branches had higher chances to be identified if the angiography of the ophthalmic artery was accompanied by the study of the external carotid system. CONCLUSION: This work provides an objective measure of how powerful angiography is to identify intraorbital arteries as well as useful references for professionals who need to operate in the orbit. PMID- 26154350 TI - Constant-intensity waves and their modulation instability in non-Hermitian potentials. AB - In all of the diverse areas of science where waves play an important role, one of the most fundamental solutions of the corresponding wave equation is a stationary wave with constant intensity. The most familiar example is that of a plane wave propagating in free space. In the presence of any Hermitian potential, a wave's constant intensity is, however, immediately destroyed due to scattering. Here we show that this fundamental restriction is conveniently lifted when working with non-Hermitian potentials. In particular, we present a whole class of waves that have constant intensity in the presence of linear as well as of nonlinear inhomogeneous media with gain and loss. These solutions allow us to study the fundamental phenomenon of modulation instability in an inhomogeneous environment. Our results pose a new challenge for the experiments on non-Hermitian scattering that have recently been put forward. PMID- 26154342 TI - Synthetic Nanoparticles for Vaccines and Immunotherapy. PMID- 26154351 TI - [Recognizing frailty in the elderly is a priority]. PMID- 26154352 TI - [Aromatherapy in nursing homes]. AB - Pierre Delaroche de Clisson hospital uses essential oils as part of its daily organisation for the treatment of pain and the development of palliative care. The setting up of this project, in nursing homes and long-term care units, is the fruit of a complex mission carried out by a multidisciplinary team, which had to take into account the risks involved and overcome a certain amount of reluctance. PMID- 26154353 TI - [Prevention of and fight against bacterial resistance]. PMID- 26154354 TI - [From the discovery of antibiotics to emerging highly drug-resistant bacteria]. AB - The discovery of antibiotics has enabled serious infections to be treated. However, bacteria resistant to several families of antibiotics and the emergence of new highly drug-resistant bacteria constitute a public health issue in France and across the world. Actions to prevent their transmission are being put in place. PMID- 26154355 TI - [The fight against bacterial resistance, a public health priority]. AB - The increase in the number of antibiotic resistant bacteria represents a major danger for the health of humans and animals. Combined with an almost complete absence of new antibiotics, it is one of the most alarming public health issues of our time. Measures must be taken in order to control the use of these drugs and safeguard their effectiveness. PMID- 26154356 TI - [A communication campaign to improve how antibiotics are used]. AB - A wide-scale information campaign, using a memorable slogan, reminded health professionals and users that the prescribing of antibiotics is not 'automatic' in the case of a viral infection. The fight against antibiotic resistant bacteria requires the consumption of these medications to be limited in order to preserve their effectiveness. PMID- 26154357 TI - [The role of hospital teams in the management of patients carrying highly drug resistant bacteria]. AB - The increase in antibiotic-resistant bacteria and emerging highly drug-resistant bacteria is resulting in alarming situations of treatment failure. In hospitals, precautionary measures to control nosocomial infections are put in place through the collaboration between caregivers, the operational hygiene team and the nosocomial infection control committee, in accordance with official recommendations. PMID- 26154358 TI - [The role of CCLINs in the event of an epidemic of multi-drug and highly resistant bacteria]. AB - The management of epidemics of multi-drug and highly resistant bacteria must be based on a structured organisation. Within each region it requires the expertise of centres for the interregional coordination of nosocomial infection control (CCLINs) and their regional branches of nosocomial infection control (Arlin) which support hospitals in reporting these types of epidemics. PMID- 26154359 TI - [Psychological impacts of being a carrier of multi-drug resistant bacteria]. AB - Learning that they are a carrier of multi-drug resistant bacteria and being placed in isolation to prevent transmission has significant psychological repercussions for the patient and their families. Through therapeutic education, caregivers adapt their support to the patient's experience, raising their awareness of prevention. PMID- 26154360 TI - [The risk of infection with patients with multi-drug resistant bacteria in the operating room]. AB - The risk of infection in the operating theatre is constant and multifactorial. It can be contained through a prevention process. The organisation, implementation, monitoring and the results of the patient pathway are all sources for the analysis of practices, quality and professional progress in order to limit the risks of transmitting multi-drug or highly resistant bacteria. PMID- 26154361 TI - [Caring for a patient carrying multi-drug resistant bacteria at home]. AB - Private practice health professionals play a role in the fight against healthcare associated infections. The management of the home care of a patient carrying multi-drug resistant bacteria reveals the weaknesses in the community-hospital link. Providing care in complete safety for the caregiver as well as the patient is a major challenge. A private practice nurse shares his experience. PMID- 26154362 TI - [The approach by nursing students to patients carrying multi-drug resistant bacteria]. PMID- 26154363 TI - [A global fight against anti-bacterial resistance]. PMID- 26154364 TI - [Clinical protocols of cooperation regarding ultrasonography]. PMID- 26154365 TI - Do open and endoscopic resection approaches to juvenile nasopharyngeal angiofibroma result in similar blood loss and recurrence rates? PMID- 26154368 TI - Facial palsy after neck arteriovenous fistula embolization. AB - Facial palsy after embolization of neck arteriovenous fistula is an extremely rare complication. In our case, complete facial palsy occurred after embolization and was successfully treated with superficial parotidectomy, vessel ligation, and plug removal. We report the first case of unusual facial palsy that developed 13 days after neck arteriovenous fistula embolization. As a result of our findings, we recommend, when a patient suffers from acute ipsilateral facial palsy after arteriovenous fistula embolization, the clinician should consider the possibility of complications of embolization, and immediate and appropriate management should be performed. PMID- 26154366 TI - The prevalence of binge drinking and receipt of provider drinking advice among US veterans with military service in Iraq or Afghanistan. AB - BACKGROUND: Binge drinking is a significant public health concern linked to a number of health and psychosocial problems. Military service in Afghanistan (OEF) and Iraq (OIF) has been associated with posttraumatic stress disorder (PTSD) and increased hazardous drinking. Brief alcohol interventions may reduce hazardous drinking but are infrequently provided to at-risk drinkers. OBJECTIVES: This study examined the association of combat exposure, PTSD symptoms, binge drinking, use of VA and non-VA healthcare services, and the incidence of provider drinking advice. METHODS: OEF/OIF veterans (n = 1087) completed measures of demographics, military history, combat exposure, PTSD symptoms, and binge drinking as part of a confidential mail survey study conducted in 2009 and 2010 (response rate = 29%). Patient report of receiving advice in the past year from a provider about their drinking was queried for frequent binge drinkers. The association of demographic variables, combat exposure, PTSD, and use of healthcare services with binge drinking and receipt of provider drinking advice was estimated using logistic regression. RESULTS: Overall, 51% of the sample reported at least one episode of binge drinking in the past year and 19% were identified as frequent binge drinkers. PTSD was related to frequent binge drinking. At-risk veterans using VA healthcare services were significantly more likely to receive provider drinking advice (50%) than veterans not using VA (13.4%). CONCLUSIONS: There is a need for increased vigilance and action to identify and counsel at-risk veterans about alcohol misuse in this population. PMID- 26154367 TI - Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release. AB - C. elegans undergoes periods of behavioral quiescence during larval molts (termed lethargus) and as adults. Little is known about the circuit mechanisms that establish these quiescent states. Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1. Here, we show that the aroused locomotion of npr-1 mutants results from the exaggerated activity in multiple classes of sensory neurons, including nociceptive (ASH), touch sensitive (ALM and PLM), and stretch sensing (DVA) neurons. These sensory neurons accelerate locomotion via both neuropeptide and glutamate release. The relative contribution of these sensory neurons to arousal differs between larval molts and adults. Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states. PMID- 26154369 TI - Effects of various irrigation/aspiration protocols on cleaning of flattened root canals. AB - This study aimed to evaluate, by means of scanning electron microscopy (SEM), the cleaning of flattened root canals, varying irrigation/aspiration protocols during biomechanical preparation. Thirdy human mandibular incisors were distributed into three groups (n = 10) according to the aspiration/irrigation protocols: conventional, conventional + brush, and apical negative pressure irrigation. Irrigation procedure was performed with 5 mL of 1% NaOCl at each change of instrument; final irrigation was conducted with 17% EDTA for 5 min. After biomechanical preparation, the roots were sectioned and prepared for SEM analysis. The images obtained were evaluated under 35* and 1,000* magnification by three calibrated examiners, following a double-blind design. All data were analyzed using Kruskal-Wallis and Dunn's post hoc tests (alpha = 0.05). Canals wherein the conventional method and apical negative pressure irrigation were employed revealed less debris, statistically different from the conventional + brush group (p < 0.05). Regarding the presence of smears, apical negative pressure irrigation was more effective in cleaning, showing lowest scores (p < 0.05), compared with the other tested protocols. Comparing each root canal third revealed that the apical portion was difficult to clean as all the tested protocols showed similar high scores (p > 0.05), both for the presence of debris and smear layer. In conclusion, although none of the studied irrigation/aspiration protocols have completely cleaned flattened root canals, apical negative pressure irrigation was more effective in smear layer removal, whereas the conventional + brush protocol was the least effective in removing the debris and smear layer. PMID- 26154370 TI - Antifungal activity of propolis against Candida species isolated from cases of chronic periodontitis. AB - This research evaluated the fungistatic and fungicidal activities of red propolis alcoholic extract (RPAE) against different Candida species isolated from chronic periodontitis cases, and compared with chlorhexidine (CHX). Nineteen samples of Candida species (C. albicans [n = 12], C. tropicalis [n = 5] and C. glabrata [n = 2]) isolated from chronic periodontitis cases were analyzed. The fungistatic and fungicidal activity of both RPAE and CHX were evaluated using fluconazole and C. parapsilosis (ATCC 6258) as a control. Fungistatic activity was analyzed based on the Clinical and Laboratory Standards Institute (CLSI) reference procedure to determine the minimum inhibitory concentrations. Fungicidal activity was established according to the absence of fungal growth on Sabouraud Dextrose Agar medium. The fungistatic and fungicidal activities of RPAE were observed, respectively, at 32-64 MUg/mL and 64-512 MUg/mL for C. albicans, 64 MUg/mL and 64 256 MUg/mL for C. glabrata, and 32-64 MUg/mL and 64 ug/mL for C. tropicalis. CHX fungistatic activity was observed at concentrations of 0.003-1.92 ug/mL for C. albicans, 1.92 ug/mL for C. glabrata, and 0.03-1.92 ug/mL for C. tropicalis. Fluconazole fungistatic activity ranged between 1-64 MUg/mL, and fungicidal activity occurred at 8-64 MUg/mL, for the three Candida species analyzed. All the Candida species were susceptible to RPAE antifungal activity, but five samples of C. albicans, one of C. tropicalis and one of C. glabrata were resistant to fluconazole antifungal activity. CHX showed fungistatic activity against all the Candida species analyzed. The antifungal potential of these substances suggests that they can be applied as an alternative treatment for diseases affected by these species. PMID- 26154371 TI - Correlation between facial types and muscle TMD in women: an anthropometric approach. AB - Temporomandibular disorders (TMD) affecting the articular disc and/or the facial muscles are common among the population, recording a higher incidence in women age 20-40 years. The aim of this study was to investigate the correlation between facial types and muscle TMD in women. This study comprised 56 women age 18 to 49 years, seeking treatment for TMD at the School of Medicine, Federal University of Sao Paulo. All of the study individuals were diagnosed with muscle TMD, based on the Research Diagnostic Criteria (RDC). Facial type was determined using the Facial Brugsch Index and classified as euryprosopic (short and/or broad), mesoprosopic (average width) and leptoprosopic (long and/or narrow). The data were submitted to the Chi-square test and ANOVA-Tukey's test to conduct the statistical analysis. The faces of 27 individuals were classified as euryprosopic (48%), 18 as mesoprosopic (32%), and 11 as leptoprosopic (20%). A statistically significant difference (Chi-square, p = 0.032) was found among the facial types, in that leptoprosopic facial types showed the lowest values for muscle TMD. A greater number (p = 0.0007) of cases of muscle TMD were observed in the 20 to 39 year-old subjects than in the subjects of other age segments. In conclusion, women with euryprosopic facial types could be more susceptible to muscle TMD. Further studies are needed to investigate this hypothesis. PMID- 26154372 TI - Prevalence and risk factors of non-carious cervical lesions related to occupational exposure to acid mists. AB - This study evaluates the prevalence and risk factors of non-carious cervical lesions (NCCLs) in a Brazilian population of workers exposed and non-exposed to acid mists and chemical products. One hundred workers (46 exposed and 54 non exposed) were evaluated in a Centro de Referencia em Saude do Trabalhador - CEREST (Worker's Health Reference Center). The workers responded to questionnaires regarding their personal information and about alcohol consumption and tobacco use. A clinical examination was conducted to evaluate the presence of NCCLs, according to WHO parameters. Statistical analyses were performed by unconditional logistic regression and multiple linear regression, with the critical level of p < 0.05. NCCLs were significantly associated with age groups (18-34, 35-44, 45-68 years). The unconditional logistic regression showed that the presence of NCCLs was better explained by age group (OR = 4.04; CI 95% 1.77 9.22) and occupational exposure to acid mists and chemical products (OR = 3.84; CI 95% 1.10-13.49), whereas the linear multiple regression revealed that NCCLs were better explained by years of smoking (p = 0.01) and age group (p = 0.04). The prevalence of NCCLs in the study population was particularly high (76.84%), and the risk factors for NCCLs were age, exposure to acid mists and smoking habit. Controlling risk factors through preventive and educative measures, allied to the use of personal protective equipment to prevent the occupational exposure to acid mists, may contribute to minimizing the prevalence of NCCLs. PMID- 26154373 TI - Oral impacts on the daily performance of Brazilians assessed using a sociodental approach: analyses of national data. AB - The aim of this study was to analyze the relationship between oral diseases and their impact on the daily performance of adult and elderly Brazilians, verify the association of oral diseases with socioeconomic and demographic features, and compare the standard estimate of need with the sociodental assessment of these same needs. The authors evaluated data from 17,398 Brazilians aged between 35-44 years and 65-74 years, taken from the cross-sectional Brazilian Oral Health Survey (Saude Bucal Brasil - SBBrasil). Regression models were applied to assess associations among impacts on daily performance and income, schooling, gender, region, use of dental services, health perception and dental disease status. McNemar's test was applied to compare standard versus impact-related estimates of need. The prevalence ratio of these impacts was associated with the sociodemographic versus health perceptions (p < 0.001) of adults and the elderly. Adults also had impacts associated with loss of periodontal attachment (p < 0.001). The prevalence of normative needs was 95.39% for adults and 99.76% for the elderly, whereas the impact-related estimate of need was 50.92% and 43.71%, respectively. The impacted-related approach had a statistically significant association with the normative estimate of need (p < 0.001). This study showed a relationship between oral impact on daily performance of adults and educational level. Sociodemographic features were also related to the impacts on both adults and the elderly, and to health perception. The impacts among the adults were related to the loss of periodontal attachment. In addition, the authors found a sizable difference between the standard versus the sociodental approach, in that the sociodental assessment needs were lower than the needs identified by the standard estimate of need. PMID- 26154374 TI - Are bovine teeth a suitable substitute for human teeth in in vitro studies to assess endotoxin load in root canals? AB - The present study aimed to determine the feasibility of using bovine teeth as a suitable alternative for human teeth, in experiments involving in vitro endotoxin contamination. Twenty bovine central incisors and 20 human single-root premolars had their dental crowns removed and root lengths set at 16 mm. Root canals were prepared up to #60 K-file size and sterilized with cobalt-60 gamma irradiation (20 kGy, 6 h). The teeth were randomly divided into four groups: G1-bovine teeth (bovine negative control, n = 10), G2-human teeth (human negative control, n = 10), G3-bovine teeth, inoculated with Escherichia coli (055:B55) LPS, and G4 human teeth inoculated with E. coli LPS. The G1 and G2 groups were exposed to apyrogenic water. After the teeth had been incubated at 37 degrees C and atmospheric humidity for 24 h, the samples of solutions in the main canals were collected with apyrogenic absorbent paper tips. LPS levels were quantified using Limulus Amebocyte Lysate assay. The data obtained were statistically analyzed using one-way ANOVA, with a significance level of 5%. A high amount of endotoxin was detected in the inoculated human teeth (G4) when compared to the sterilized teeth (G2), as well as in the inoculated bovine teeth (G3) when compared to the inoculated human teeth (G4). However, there was no statistical difference between bovine teeth before and after the E. coli endotoxin inoculation. Therefore, under the mentioned experimental conditions, the use of bovine teeth should not be a choice for laboratory research on endotoxin contamination. PMID- 26154375 TI - Evaluation of a feasible educational intervention in preventing early childhood caries. AB - Early childhood caries (ECC) in the primary dentition of preschoolers remains high. Young children have limited access to oral healthcare, and oral health education (OHE) measures can be a valuable tool to prevent caries in this population. The aim of this study was to evaluate the impact of an early educational intervention on ECC prevention. The study group (SG) comprised 271 children aged 0-12 months and their mothers, who attended 12 selected public health centers (PHC). The SG received oral health instructions from a pamphlet and by verbal explanation of some topics. One year later, a similar sample of children from another 12 PHCs were selected to serve as the control (CG; n = 251). The children were examined to determine their caries status: decayed = cavitated and/or white spot lesion (maxillary anterior surface); missing; and filled surface index > 0. There was a one-year follow-up. Socioeconomic and demographic information was collected. Logistic regression was used to estimate the effects of the educational intervention on the ECC odds. A sample of 445 (SG = 194 and CG = 251) children remained to the end of the study and were examined. The prevalence of caries was 12.9% in the SG and 17.9% in the CG. The odds of caries were 80% higher in the CG than in the SG (p = 0.037). The strategy of providing OHE from a pamphlet and with a brief verbal instruction to mothers during their child's first year of life can constitute a valuable tool for ECC prevention. PMID- 26154376 TI - Root and canal symmetry in the mandibular anterior teeth of patients attending a dental clinic: CBCT study. AB - The aims of this study were to evaluate the number of roots/root canals in the mandibular anterior teeth of a Turkish population, to assess the relationship between gender or age and the frequency of two canals in a single root, and to determine the symmetry in root/root canal numbers between contralateral sides among patients. Cone-beam computed tomography images (n = 1128; 6253 teeth) taken at the Department of Dentomaxillofacial Radiology of the Faculty of Dentistry of Gazi University were examined by three observers and a supervisor, all of whom were blinded to patient gender and age. Axial, sagittal, and cross-sectional slices with a thickness of 1 mm were used. Numbers of roots and canals for each type of tooth were recorded. Most teeth had a single root and single root canal. Roots with two canals were more frequent in the incisors (14.9%, 17.2%, and 6.1% of the central incisors, lateral incisors, and canines, respectively). Teeth with two roots were more frequent in the canines (3.1% vs. 0% or 0.1%). Females more often had canines with double root canals (p < 0.001). When at least one tooth had two root canals, bilateral symmetry between contralateral teeth was found in 45.0%, 29.0%, and 28.0% of cases for central incisors, lateral incisors, and canines, respectively. Patients older than 56 years had fewer teeth with double root canals (p <= 0.001). A small proportion of the mandibular anterior teeth had two roots or root canals. Double root canals were mostly unilateral. Age and gender were associated with the number of root canals. PMID- 26154377 TI - Bonding stability of adhesive systems to eroded dentin. AB - This in vitro study evaluated the immediate and 6 months microshear bond strength (uSBS) of different adhesive systems to sound and eroded dentin. Sixty bovine incisors were embedded in acrylic resin and ground to obtain flat buccal dentin surfaces. Specimens were randomly allocated into two groups: sound dentin (immersion in artificial saliva) and eroded dentin (erosive challenge following a pH cycling model comprising 4 */day Sprite Light(r) drink for 10 days). Then, specimens were reassigned according to the adhesive system: etch-and-rinse adhesive (Adper Single Bond), two-step self-etch system (Clearfil SE Bond), or one-step self-etch adhesive (Adper Easy One). Polyethylene tubes with an internal diameter of 0.76 mm were placed over pre-treated dentin and filled with resin composite (Z250). Half of the specimens were evaluated by the uSBS test after 24 h, and the other half 6 months later, after water storage at 37 degrees C. Failure mode was evaluated using a stereomicroscope (400 *). Data were analyzed by three-way repeated measures analysis of variance and Tukey's post hoc tests (alpha = 0.05). After 6 months of water aging, marked reductions in uSBS values were observed, irrespective of the substrate. The uSBS values for eroded dentin were lower than those obtained for sound dentin. No difference in bonding effectiveness was observed among adhesive systems. For all groups, adhesive/mixed failure was observed. In conclusion, eroded dentin compromises the bonding quality of adhesive systems over time. PMID- 26154378 TI - Periodontal status of Pakistani orthodontic patients. AB - The objective of this study was to evaluate and compare the periodontal status of orthodontic patients and non-orthodontic patients, aged 15-28 years, of both genders. The cross-sectional study included 100 orthodontic and 100 non orthodontic patients evaluated using a Community Periodontal Index for Treatment Need (CPITN) probe on the index teeth. A questionnaire was distributed to the participants to assess and evaluate the use of oral hygiene aids. The data were analyzed using SPSS version 17, and various comparisons were performed using the chi-square test. The study revealed that there was a statistically significant association in CPITN scores between the orthodontic and non-orthodontic patients (p < 0.01). The study showed that patients undergoing orthodontic treatment have increased plaque accumulation and probing depth resulting in periodontal tissue destruction. Proper oral hygiene practices and interdental aids should be employed to control plaque. PMID- 26154379 TI - Entrustable professional activities. PMID- 26154383 TI - Response to 'Dressed to regress but not for success'. PMID- 26154384 TI - Geometric Mixing, Peristalsis, and the Geometric Phase of the Stomach. AB - Mixing fluid in a container at low Reynolds number--in an inertialess environment -is not a trivial task. Reciprocating motions merely lead to cycles of mixing and unmixing, so continuous rotation, as used in many technological applications, would appear to be necessary. However, there is another solution: movement of the walls in a cyclical fashion to introduce a geometric phase. We show using journal bearing flow as a model that such geometric mixing is a general tool for using deformable boundaries that return to the same position to mix fluid at low Reynolds number. We then simulate a biological example: we show that mixing in the stomach functions because of the "belly phase," peristaltic movement of the walls in a cyclical fashion introduces a geometric phase that avoids unmixing. PMID- 26154385 TI - Primary multifocal myxopapillary ependymoma of the filum terminale. AB - BACKGROUND: Myxopapillary ependymoma (MPE) is a rare variant of ependymoma usually occurring in the conus medullaris or the filum terminale. It is usually a single encapsulated lesion. The aim of this study was to describe patients with primary multifocal MPE of the filum terminale. METHODS: In this retrospective study, medical records of 22 patients with spinal MPE who underwent surgical treatment in our hospital between January 2003 and January 2010 were enrolled. The study included 14 males and 8 females with age range from 11 to 66 years. There were 14 adult patients and 8 pediatric patients. The clinical presentation was low back pain (LBP), radiculopathy, focal neurological deficit and cranial nerve palsy. RESULTS: Four cases presented with primary multifocal MPE at the filum terminale. All of them had chronic LBP for at least 2-3 years. Three patients had lower extremity radiculopathy and one had urinary incontinence upon presentation. On magnetic resonance imaging (MRI), three patients presented with two lesions and one patient presented with three lesions at different spinal levels (a total of 9 MPEs). All lesions showed enhancement following gadolinium administration on MRI. For 6 tumors en bloc resection was performed. Three lesions were removed gross totally in a piece-meal fashion. Following the surgical management, no postoperative complication occurred. Three patients underwent radiotherapy (RT. On an average follow-up of 6 years with clinical and MRI imaging, no recurrence was detected and symptoms of LBP and neurologic findings improved after 2 months. CONCLUSIONS: Primary multifocal MPE is an extremely rare event occurring in the conus medullaris or filum terminale. The exact pathogenesis of this condition is unclear. Multifocal MPE may be due to multifocal growth of tumors, early stage of growth of a giant tumor or drop metastasis of tumor in the subarachnoid space. En bloc resection or piecemeal resection with radiotherapy were associated with satisfactory outcome without recurrence. PMID- 26154386 TI - Decision Rightness and Emotional Responses to Abortion in the United States: A Longitudinal Study. AB - BACKGROUND: Arguments that abortion causes women emotional harm are used to regulate abortion, particularly later procedures, in the United States. However, existing research is inconclusive. We examined women's emotions and reports of whether the abortion decision was the right one for them over the three years after having an induced abortion. METHODS: We recruited a cohort of women seeking abortions between 2008-2010 at 30 facilities across the United States, selected based on having the latest gestational age limit within 150 miles. Two groups of women (n=667) were followed prospectively for three years: women having first trimester procedures and women terminating pregnancies within two weeks under facilities' gestational age limits at the same facilities. Participants completed semiannual phone surveys to assess whether they felt that having the abortion was the right decision for them; negative emotions (regret, anger, guilt, sadness) about the abortion; and positive emotions (relief, happiness). Multivariable mixed-effects models were used to examine changes in each outcome over time, to compare the two groups, and to identify associated factors. RESULTS: The predicted probability of reporting that abortion was the right decision was over 99% at all time points over three years. Women with more planned pregnancies and who had more difficulty deciding to terminate the pregnancy had lower odds of reporting the abortion was the right decision (aOR=0.71 [0.60, 0.85] and 0.46 [0.36, 0.64], respectively). Both negative and positive emotions declined over time, with no differences between women having procedures near gestational age limits versus first-trimester abortions. Higher perceived community abortion stigma and lower social support were associated with more negative emotions (b=0.45 [0.31, 0.58] and b=-0.61 [-0.93, -0.29], respectively). CONCLUSIONS: Women experienced decreasing emotional intensity over time, and the overwhelming majority of women felt that termination was the right decision for them over three years. Emotional support may be beneficial for women having abortions who report intended pregnancies or difficulty deciding. PMID- 26154387 TI - Long-Term Endurance Exercise in Humans Stimulates Cell Fusion of Myoblasts along with Fusogenic Endogenous Retroviral Genes In Vivo. AB - Myogenesis is defined as growth, differentiation and repair of muscles where cell fusion of myoblasts to multinucleated myofibers is one major characteristic. Other cell fusion events in humans are found with bone resorbing osteoclasts and placental syncytiotrophoblasts. No unifying gene regulation for natural cell fusions has been found. We analyzed skeletal muscle biopsies of competitive cyclists for muscle-specific attributes and expression of human endogenous retrovirus (ERV) envelope genes due to their involvement in cell fusion of osteoclasts and syncytiotrophoblasts. Comparing muscle biopsies from post- with the pre-competitive seasons a significant 2.25-fold increase of myonuclei/mm fiber, a 2.38-fold decrease of fiber area/nucleus and a 3.1-fold decrease of satellite cells (SCs) occurred. We propose that during the pre-competitive season SC proliferation occurred following with increased cell fusion during the competitive season. Expression of twenty-two envelope genes of muscle biopsies demonstrated a significant increase of putative muscle-cell fusogenic genes Syncytin-1 and Syncytin-3, but also for the non-fusogenic erv3. Immunohistochemistry analyses showed that Syncytin-1 mainly localized to the sarcolemma of myofibers positive for myosin heavy-chain isotypes. Cellular receptors SLC1A4 and SLC1A5 of Syncytin-1 showed significant decrease of expression in post-competitive muscles compared with the pre-competitive season, but only SLC1A4 protein expression localized throughout the myofiber. Erv3 protein was strongly expressed throughout the myofiber, whereas envK1-7 localized to SC nuclei and myonuclei. Syncytin-1 transcription factors, PPARgamma and RXRalpha, showed no protein expression in the myofiber, whereas the pCREB-Ser133 activator of Syncytin-1 was enriched to SC nuclei and myonuclei. Syncytin-1, Syncytin-3, SLC1A4 and PAX7 gene regulations along with MyoD1 and myogenin were verified during proliferating or actively-fusing human primary myoblast cell cultures, resembling muscle biopsies of cyclists. Myoblast treatment with anti Synycytin-1 abrogated cell fusion in vitro. Our findings support functional roles for ERV envelope proteins, especially Syncytin-1, contributing to cell fusion of myotubes. PMID- 26154389 TI - Fracture Incidence in Adult Kidney Transplant Recipients. AB - BACKGROUND: It remains uncertain whether kidney transplant recipients are a high risk group for fracture. METHODS: We conducted a cohort study using Ontario, Canada health care databases to estimate the 3-, 5- and 10-year cumulative incidence of nonvertebral fracture (proximal humerus, forearm, hip) in adult kidney transplant recipients between 1994 and 2009, stratifying by sex and age (<50 versus >=50 years) at transplant. We also assessed the 3-year cumulative incidence of all fracture locations (excluding skull, toes, and fingers) and falls, 10-year cumulative incidence of hip fracture alone, and nonvertebral fracture incidence in recipients compared to nontransplant reference groups matched on age, sex, and cohort entry year. We studied 4821 recipients (median age, 50 years). RESULTS: Among the age and sex strata, female recipients aged 50 years or older had the highest 3-year cumulative incidence of nonvertebral fracture (3.1%; 95% confidence interval [95% CI], 2.1-4.4%). Recipients had a higher 3-year cumulative incidence of nonvertebral fracture (1.6%; 95% CI, 1.3 2.0%) compared to the general population with no previous nonvertebral fracture (0.5%; 95% CI, 0.4-0.6%; P < 0.0001) and nondialysis chronic kidney disease (1.1%; 95% CI, 0.9-1.2%; P = 0.03), but a lower fracture incidence than the general population with a previous nonvertebral fracture (2.3%; 95% CI, 1.9-2.8%; P = 0.007). The 10-year cumulative incidence of hip fracture in all recipients was 1.7% (>=3% defined as high risk in clinical guidelines). CONCLUSIONS: Kidney transplant recipients may have a lower fracture risk than previously suggested in the literature. Results inform our understanding of fracture incidence after kidney transplantation and how it compares to nontransplant populations. PMID- 26154388 TI - Transcriptional Perturbations in Graft Rejection. AB - BACKGROUND: Understanding the regulatory interplay of relevant microRNAs (miRNAs) and messenger RNAs (mRNAs) in the rejecting allograft will result in a better understanding of the molecular pathophysiology of alloimmune injury. METHODS: One hundred sixty-seven allograft biopsies, with (n = 47) and without (n = 120) central histology for Banff scored acute rejection (AR), were transcriptionally profiled for mRNA and miRNA by whole genome microarrays and multiplexed microfluidic quantitative polymerase chain reaction, respectively. A customized database was curated (GO-Elite) and used to identify AR-specific dysregulated mRNAs and the role of perturbations of their relevant miRNAs targets during AR. RESULTS: The AR-specific changes in 1035 specific mRNAs were mirrored by AR specific perturbations in 9 relevant miRNAs as predicted by Go-Elite and were regulated specifically by p53 and forkhead box P3. Infiltrating lymphocytes and the renal tubules drove the miRNA tissue pertubations in rejection, involving message degradation and transcriptional/translational activation. The expression of many of these miRNAs significantly associated with the intensity of the Banff scored interstitial inflammation and tubulitis. CONCLUSIONS: There is a highly regulated interplay between specific mRNA/miRNAs in allograft rejection that drive both immune-mediated injury and tissue repair during AR. PMID- 26154390 TI - Use of Elderly Allografts in Liver Transplantation. AB - INTRODUCTION: The use of liver allografts from elderly donors (>=70 years) has increased because of organ shortage and increased life expectancy. The aim of this study is to evaluate the current utilization of elderly donors in United States, recipient selection, and their posttransplant outcomes. METHODS: A linkage between Scientific Registry of Transplant Recipients and University HealthSystem Consortium databases was performed. Between January 2007 and December 2011, 12,445 liver transplant (LT) recipients were identified and divided into 2 cohorts based on donor age: 70 years or older (n = 540) and younger than 60 years (n = 10,473). RESULTS: Elderly donors accounted for 4.3% of all donors used in the 5-year period. When compared to younger donors, elderly donors were more likely to be women, shared regionally or nationally, and used at higher volume centers. Elderly donor allografts were less likely to be used in recipients with model of end-stage liver disease score higher than 27 (13.2% vs. 23.0%, P < 0.001), hospitalized (16.8% vs. 21.7%, P = 0.03), or on hemodialysis at time of transplant (2.6% vs. 8.2%, P < 0.001). Both recipient groups had similar perioperative mortality, 30-day readmission rates, and short-term patient survival. In the multivariate analysis, including recipient, donor, center and regional factors, donor age 70 years or older was associated with slightly increased risk of graft loss (hazard ratio, 1.3; 95% confidence interval, 1.08 1.56; P = 0.005). CONCLUSIONS: The current trend toward the use of elderly donors in liver transplant recipients with low model of end-stage liver disease scores (<27), without hepatitis C, not hospitalized and not on dialysis, is associated with acceptable perioperative outcomes, patient survival, and slightly worse graft survival. PMID- 26154391 TI - microRNA in Transplantation: Small in Name Only. PMID- 26154392 TI - Bilateral Forearm Transplantation in Mexico: 2-Year Outcomes. AB - BACKGROUND: Patients with proximal forearm and arm transplantation have obtained and/or maintained function of the elbow joint and full active range of motion of the extrinsic muscles of the hand, but with diminished protective sensibility and a lack of good function of the intrinsic muscles. These patients have improved function, as measured by the Disabilities of the Arm, Shoulder and Hand questionnaire. METHODS: We report the case of a 52-year-old man who suffered a high-voltage electrical burn requiring amputation of his upper limbs. He underwent bilateral proximal forearm transplantation in Mexico City in May 2012. RESULTS: At 2-year follow-up, immunosuppressive treatment has not led to metabolic, oncologic, or infectious complications. Keloid scars developed at the graft-recipient interface. There have been 4 acute rejections: the fourth was treated with methylprednisolone, rituximab, and immunoglobulin. Chronic rejection has not been detected. The extrinsic muscles of the wrist and digits have good function. Although the intrinsic muscles demonstrated electrical activity 15 months postoperatively, clinically, they are nonuseful. After 2 years, hand function is sufficient to allow the patient to grasp lightweight and medium-sized objects. The patient's Disabilities of the Arm, Shoulder and Hand questionnaire score improved from 50.00 points to 30.83 points, and his Hand Transplantation Score System rating is good, at 69/73 (right/left) of 100. The patient and his family are very satisfied with the functional and aesthetic outcomes. CONCLUSIONS: Upper arm or proximal forearm transplantation is a reconstructive option for patients who have experienced amputation because of trauma. PMID- 26154394 TI - Advanced oxidation protein products in predicting acute kidney injury following cardiac surgery. AB - To test the hypothesis whether serum advanced oxidation protein products (AOPP) are associated with increased acute kidney injury (AKI) after cardiopulmonary bypass (CPB) and could serve as a biomarker in this aspect, we performed a prospective cohort study. Thirty-five (22.3%) patients developed AKI, and 32 age- and gender-matched patients without AKI were selected as control. Serum AOPP 1 h after CPB were significantly higher among AKI patients compared with non-AKI patients (81.8 +/- 18.6 versus 67.4 +/- 12.5 MUmol/L, p < 0.001), with an area under the receiver-operating characteristic (ROC) curve of 0.714. An optimal serum AOPP 1 h after CPB cutoff of 69.9 MUmol/L had a sensitivity of 74%, specificity of 63% and a positive predictive value of 68% for predicting AKI. These results demonstrated that serum AOPP might be an early biomarker for AKI after CPB. PMID- 26154393 TI - Chromogranin A levels and mortality in patients with severe sepsis. AB - CONTEXT: Chromogranin A (CgA) is a novel biomarker with potential to assess mortality risk of patients with severe sepsis. OBJECTIVE: Assess association of CgA levels and mortality risk of severely septic patients. METHODS: Serum CgA levels were measured in 50 hospitalized, severely septic patients with organ failure <48 h. RESULTS: Higher CgA levels trended toward higher ICU and hospital mortality. Patients without cardiovascular disease who died in the ICU had higher median (IQR) CgA levels 602.3 (343.3, 1134.3) ng/ml versus 205.5 (130.7, 325.9) ng/ml, p = 0.01. CONCLUSIONS: High CgA levels predict ICU mortality in severely septic patients without prior cardiovascular disease. PMID- 26154395 TI - Usage of Accessibility Options for the iPhone and iPad in a Visually Impaired Population. AB - PURPOSE: The iPad and iPhone have a number of low-vision accessibility features including Siri Voice Assistant, Large Text, Zoom Magnification, Invert Colors, Voice Over, and Speech Selection. We studied their usage within a low-vision population. METHODS: Patients were recruited to participate in an IRB-approved survey regarding their usage of the iPad and/or iPhone. Participants met one of the following criteria: best corrected visual acuity (BCVA) of 20/60 or worse, or significant peripheral visual field defects. RESULTS: Thirty-three low-vision patients agreed to participate (mean age 54.3 years). There were 18 different diagnoses represented and the average visual acuity of respondents was 20/119 in the right eye and 20/133 in the left eye. The most commonly used vision accessibility features were Zoom Magnification and Large Text. CONCLUSIONS: Although many patients are using the low-vision accessibility features, few are receiving training or recommendations from their eye care specialist. PMID- 26154396 TI - Zoledronate induces osteonecrosis of the jaw in sheep. AB - INTRODUCTION: The treatment of bisphosphonate-related osteonecrosis of the jaw has become routine in maxillofacial hospitals. However, the etiopathology has not yet been fully understood. The aim of this study was to develop a large animal model for medication-related osteonecrosis of the jaw (MRONJ). MATERIAL AND METHODS: Eight Swiss mountain sheep were randomly assigned into two groups. Group I received 0.075 mg/kg zoledronate (ZOL) intravenously every third week for 16 weeks. After 16 weeks, extraction of the first and second lower left premolar was performed. Group II underwent surgery and no ZOL was administered. After surgery, Group I continued to receive ZOL infusions; after 16 weeks, all animals were euthanized. The jaw bones were investigated macroscopically, radiographically (computed tomography) and histologically. RESULTS: Osteonecrosis of the jaw was observed at all extraction sites in all the animals receiving ZOL, and at none of the sites in animals without ZOL. All ZOL-treated animals spontaneously developed exposed bone lesions in the oral cavity at sites where no surgical intervention was performed. CT imaging shows persistent alveolar extraction sockets 16 weeks after surgery in all animals of the ZOL-group, and healed alveolar extraction sockets in non-ZOL-treated animals. CONCLUSION: Sheep treated with ZOL reproducibly demonstrated osteonecrosis of the jaw after tooth extraction, and spontaneous development of exposed bone in the oral cavity at sites where no manipulation was performed. This animal model can be used for further research in the fields of BP-ONJ etiopathology, oral implantology, bone and fracture healing and periodontology. PMID- 26154397 TI - Salvage treatment of hemorrhagic arteriovenous malformations in jaws. AB - OBJECTIVE: To present our clinical experience on embolotherapy of arteriovenous malformations (AVMs) in jaws with acute hemorrhage. MATERIALS AND METHODS: Twelve patients with a history of hemorrhage were selected for this study. Continuous interdental sling suture, digital pressure on the extraction socket, and iodoform gauze packed into the socket and fixed with sutures to the adjacent gum were used for temporary hemostasis before embolization. Fiberoptic bronchoscopy was used in all cases to facilitate endotracheal intubation. Absolute ethanol combined with coils was used as method of embolization. RESULTS: Eight patients presented with intermittent interdental gum bleeding or controlled hemostasis before embolization. Four patients presented with torrential hemorrhage around the tooth, controlled by continuous pressure on the tooth and bilateral gum for temporary hemostasis. All patients were successfully salvaged before embolization. Ten of 12 patients were cured, and 2 had partial remission. Follow up ranged from 12 to 26 months (mean, 16.5 months) for all patients, and there was no recurrence of the lesions. CONCLUSIONS: The treatment of hemorrhagic AVMs of the jaw requires a multidisciplinary team approach; such cases can be successfully salvaged and stably controlled by embolization with coils and absolute ethanol. PMID- 26154398 TI - Correlation of changes in the mandible and retina/choroid vasculature of a rat model of BRONJ. AB - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) causes bones of the mandible and maxilla to become necrotic and protrude into the oral cavity. Compromised blood supply to bone is also a feature of BRONJ. The design of this study was first to use our established technique of molar extraction and IV bisphosphonate injection to produce features of BRONJ in rats that mimic the human disease; second to confirm vascular changes in the mandible and eye using micro-CT of vascular casts, and image analysis of retina/choroid images; and third to show parallel bisphosphonate-induced changes in the structure and markers of the vasculature of the bone and eye. The results of this study show structural changes in the eye and mandible as well as biochemical changes including the up-regulation of VEGF in response to the bisphosphonate-associated ischemia. These changes are not associated with angiogenesis in either the eye or mandible as determined by reduced vascular complexity. These results suggest that observations of direct changes to the vasculature in the retina/choroid structures of the eye in patients taking bisphosphonates could serve as a window to the progression of debilitating changes occurring as a result of bisphosphonate therapy. PMID- 26154399 TI - Alkaline pH sensor molecules. AB - Animals can survive only within a narrow pH range. This requires continual monitoring of environmental and body-fluid pH. Although a variety of acidic pH sensor molecules have been reported, alkaline pH sensor function is not well understood. This Review describes neuronal alkaline pH sensors, grouped according to whether they monitor extracellular or intracellular alkaline pH. Extracellular sensors include the receptor-type guanylyl cyclase, the insulin receptor-related receptor, ligand-gated Cl- channels, connexin hemichannels, two-pore-domain K+ channels, and transient receptor potential (TRP) channels. Intracellular sensors include TRP channels and gap junction channels. Identification of molecular mechanisms underlying alkaline pH sensing is crucial for understanding how animals respond to environmental alkaline pH and how body-fluid pH is maintained within a narrow range. PMID- 26154400 TI - Defect properties of cobalt-doped hexagonal barium titanate ceramics. AB - X-ray diffraction (XRD) patterns, electron paramagnetic resonance (EPR) powder spectra (9 and 34 GHz) and the magnetic susceptibility of BaTiO3 + 0.04 BaO + x/2 Co2O3 (0.001 ? x ? 0.02) ceramics were studied to investigate the incorporation of Co ions in the BaTiO3 lattice and their valence states as well as the development of the hexagonal phase (6H modification) in dependence on doping level x and sintering temperature Ts. At Ts = 1400 degrees C the 6H modification begins to occur at a nominal Co concentration x of about 0.001 and for x > 0.005 the samples are completely hexagonal at room temperature. Two different EPR spectra were observed in the 6H modification of BaTiO3, which were both assigned to paramagnetic Co(2+) ions located at the two crystallographically non equivalent Ti sites in 6H-BaTiO3. The EPR g tensor values as well as the molar paramagnetic susceptibility, measured in the temperature range 5 K-300 K at a magnetic field of 9 T, were analyzed in the framework of the ligand field theory using the program CONCORD. The combination of EPR and magnetic measurements reveals that in air-sintered 6H BaTiO3, the incorporated Co occurs as a mixture of paramagnetic Co(2+) and diamagnetic Co(3+) ions, whereas in samples annealed in reducing atmosphere the majority of Co is in the divalent state. The occurrence of Co(4+) can be excluded for all investigated samples. The sample color caused by Co(2+) and Co(3+) ions is beige/light yellow and dark grey/black, respectively. The majority of the Co(2+) ions substitutes Ti in the exclusively corner-sharing oxygen octahedra possessing nearly cubic symmetry. The corresponding ligand field parameter [Formula: see text] amounts to about -28 000 cm(-1) (Wybourne notation, 10Dq ~ 20 000 cm(-1)). In the reduced samples nearly 5% of the detected Co(2+) ions occupy the Ti site in the face-sharing oxygen octahedra, which are significantly trigonally distorted. The negative sign of the obtained ligand field parameter [Formula: see text] ~ -7300 cm(-1) reflects a compression of this octahedron in direction of the hexagonal c-axis. PMID- 26154401 TI - Parasitic Currents Caused by Different Ionic and Electronic Conductivities in Fuel Cell Anodes. AB - The electrodes in fuel cells simultaneously realize electric and ionic conductivity. In the case of acidic polymer electrolytes, the electrodes are typically made of composites of carbon-supported catalyst and Nafion polymer electrolyte binder. In this study, the interaction of the proton conduction, the electron conduction, and the electrochemical hydrogen conversion in such composite electrode materials was examined. Exposed to a hydrogen atmosphere, these composites displayed up to 10-fold smaller resistivities for the proton conduction than that of Nafion membranes. This effect was ascribed to the simultaneously occurring electrochemical hydrogen oxidation and evolution inside the composite samples, which are driven by different proton and electron resistivities. The parasitic electrochemical currents resulting were postulated to occur in the anode of fuel cells with polymer, solid oxide, or liquid alkaline electrolytes, when the ohmic drop of the ion conduction in the anode is higher with the anodic kinetic overvoltage (as illustrated in the graphical abstract). In this case, the parasitic electrochemical currents increase the anodic kinetic overpotential and the ohmic drop in the anode. Thinner fuel cell anodes with smaller ohmic drops for the ion conduction may reduce the parasitic electrochemical currents. PMID- 26154403 TI - Aerobic Nickel-Catalyzed Hydroxysulfonylation of Alkenes Using Sodium Sulfinates. AB - Nickel-catalyzed hydroxysulfonylation of alkenes was achieved using sodium sulfinates under air atmosphere. The procedure enabled the selective synthesis of beta-hydroxysulfones in good yields and suppressed the formation of beta ketosulfones. On the contrary, sulfonylation of alkynes with sodium sulfonates afforded only beta-ketosulfones. PMID- 26154402 TI - Live Video Diet and Exercise Intervention in Overweight and Obese Youth: Adherence and Cardiovascular Health. AB - OBJECTIVE: To evaluate adherence of overweight and obese adolescents to a live video lifestyle intervention. The impact on vascular and functional health was also assessed. STUDY DESIGN: Twenty adolescents 14.5 +/- 2.1 years of age with body mass index z-score 1.94 +/- 0.43 were enrolled. The 12-week intervention included 3-times-weekly videoconference sessions with a trainer and weekly diet consultations. Adherence was evaluated by completion rate and percentage of sessions attended. Vascular health indices and traditional cardiovascular risk factors were obtained at baseline and study end. RESULTS: Seventeen participants (85%) completed the intervention. The participants attended 93 +/- 11% of scheduled sessions. Reasons for absences included illness/injury (23%), school activities (21%), holidays (18%), forgetting the appointment (8%), Internet connectivity issues (7%), and family emergency (7%). Significant changes were observed in waist-hip ratio (0.87 +/- 0.08 vs 0.84 +/- 0.08, P = .03), total (159 +/- 27 vs 147 +/- 23 mg/dL, P = .004) and low-density lipoprotein cholesterol levels (91 +/- 20 vs 81 +/- 18 mg/dL, P = .004), volume of inspired oxygen per heartbeat at peak exercise (69 +/- 16 vs 72 +/- 15%, P = .01), and functional movement score (13 +/- 2 vs 17 +/- 1, P < .001). Participants with abnormal vascular function at baseline showed improvement in endothelial function and arterial stiffness indices (P = .01 and P = .04, respectively). CONCLUSIONS: A 12 week live video intervention promotes adherence among overweight and obese adolescents and shows promise for improving vascular and functional health. Integrating telehealth into preventive care has the potential to improve cardiovascular health in the youth at risk. PMID- 26154404 TI - Molecular characterization of the Israeli B. bigemina vaccine strain and field isolates. AB - The present study demonstrated the genetic character of the Israeli Babesia bigemina vaccine strain and field isolates, based on rap-1a and rap-1c gene sequences. The RAP-1a of blood-derived Israeli B. bigemina field isolates shared 100% amino acid sequence identity. However, comparison of RAP-1c from various Israeli B. bigemina field isolates revealed that the total sequence identity among the field isolates ranged from 98.2 to 100%. High identity was observed when RAP-1a sequences from the Israeli vaccine strain and field isolates were compared with RAP-1a from Egypt, Syria, Mexico and South Africa, while, the Israeli RAP-1c sequences showed the highest identity to the Mexican isolate JG-29 and to the PR isolate from Puerto-Rico. Based on sequence variations between the rap-1a of the vaccine strain and that of the field isolate, and between the rap 1c of the vaccine strain and that of the field isolates, nPCR-RFLP procedures were developed that enable, for the first time differentiation between the Israeli B. bigemina vaccine strain and field-infection isolates. These assays could serve as fast and sensitive methods for detection and differentiation between Israeli B. bigemina vaccine strains and field isolates, as well as for epidemiological investigations. PMID- 26154405 TI - Metagenomic sequencing reveals altered metabolic pathways in the oral microbiota of sailors during a long sea voyage. AB - Seafaring is a difficult occupation, and sailors face higher health risks than individuals on land. Commensal microbiota participates in the host immune system and metabolism, reflecting the host's health condition. However, the interaction mechanisms between the microbiota and the host's health condition remain unclear. This study reports the influence of long sea voyages on human health by utilising a metagenomic analysis of variation in the microbiota of the buccal mucosa. Paired samples collected before and after a sea-voyage were analysed. After more than 120 days of ocean sailing, the oral microbial diversity of sailors was reduced by approximately 5 fold, and the levels of several pathogens (e.g., Streptococcus pneumonia) increased. Moreover, 69.46% of the identified microbial sequences were unclassified microbiota. Notably, several metabolic pathways were dramatically decreased, including folate biosynthesis, carbohydrate, lipid and amino acid pathways. Clinical examination of the hosts confirmed the identified metabolic changes, as demonstrated by decreased serum levels of haemoglobin and folic acid, a decreased neutrophil-to-lymphocyte ratio, and increased levels of triglycerides, cholesterol and homocysteine, which are consistent with the observed microbial variation. Our study suggests that oral mucosal bacteria may reflect host health conditions and could provide approaches for improving the health of sailors. PMID- 26154406 TI - Regulation at multiple levels control the expression of folate transporters in liver cells in conditions of ethanol exposure and folate deficiency. AB - Complex regulatory mechanisms control the expression of folate transporters within cells. Liver is the primary reserve of the folate stores within the body. As excessive alcohol consumption or inefficient dietary folate intake are known to create folate deficiency, so therefore the current study was designed to explore various regulatory mechanisms controlling the expression of folate transport in liver cells in conditions of ethanol exposure and folate deficiency. In order to see whether the effects mediated by the treatments are reversible or not, ethanol removal, and folate repletion was done after ethanol exposure and folate deficiency treatment respectively. Folate deficiency resulted an increase, whereas ethanol treatment decreased the folic acid uptake within the cells. The alterations in folic acid uptake were in agreement with the observed changes in the expression of folate transporters. Ethanol exposure resulted an increase in promoter methylation of reduced folate carrier; however, folate deficiency had no effect. The effects produced by ethanol exposure and folate deficiency were found to be reversible in nature as depicted in case of ethanol removal and folate repletion group. Rate of synthesis of folate transporters was found to be increased whereas half lives of mRNA of folate transporters was found to be decreased on folate deficiency treatment and reverse was the case on ethanol treatment. Overall, alteration in the expression of folate transporters under ethanol exposure and folate deficient conditions can be attributed to those regulatory mechanisms which work at the mRNA level. PMID- 26154407 TI - PET-CT for detecting the undetected in the ICU. PMID- 26154408 TI - Early lactate clearance-guided therapy in patients with sepsis: a meta-analysis with trial sequential analysis of randomized controlled trials. PMID- 26154409 TI - IL-17A and its homologs IL-25/IL-17E recruit the c-RAF/S6 kinase pathway and the generation of pro-oncogenic LMW-E in breast cancer cells. AB - Pro-inflammatory IL-17 cytokines were initially described for their pathogenic role in chronic inflammatory diseases and subsequent accumulating evidence indicated their involvement in carcinogenesis. In the present study we report that IL-17A and IL-17E receptors subunits mRNA expressions are upregulated in breast cancers versus normal samples. IL-17E, which is undetectable in most normal breast tissues tested, seems more expressed in some tumors. Investigation of the molecular signaling following stimulation of human breast cancer cell lines with IL-17A and IL-17E showed that both cytokines induced the phosphorylation of c-RAF, ERK1/2 and p70 S6 Kinase were involved in the proliferation and survival of tumor cells. Accordingly, IL-17A and IL-17E promoted resistance to Docetaxel and failed to induce apoptosis as previously reported for IL-17E. Interestingly, we also revealed that both cytokines induced the generation of tumorogenic low molecular weight forms of cyclin E (LMW-E), which high levels correlated strongly with a poor survival in breast cancer patients. These results show for the first time some of the molecular pathways activated by IL-17A and IL-17E that may participate to their pro-oncogenic activity in breast cancers. PMID- 26154412 TI - Expectations About Ethnic Peer Group Inclusivity: The Role of Shared Interests, Group Norms, and Stereotypes. AB - This study investigated three factors that contribute to social exclusion: group norms, individual characteristics, and stereotypes. Non-Arab American 12- and 16 year-olds (N = 199) judged their expectations about the inclusivity of Arab American and non-Arab American peer groups toward new peers characterized by: (a) different ethnic identity but similar interests (e.g., hobbies) and (b) same ethnic identity but different interests. Participants expected that when groups had exclusive norms, Arab American peers would base inclusion decisions on ethnic identity, but that their own non-Arab group would base decisions on shared interests. Participants who reported stereotypes expected their in-group to be ethnically less inclusive. With age, ethnic-based exclusion increased. The findings are discussed in light of current research on developmental intergroup relationships. PMID- 26154413 TI - Screening for Type 2 Diabetes and Dysglycemia in Saudi Arabia: Development and Validation of Risk Scores. AB - OBJECTIVE: The prevalence of type 2 diabetes in Saudi Arabia is the highest worldwide after excluding small island nations. We developed and validated a noninvasive screening test based on demographic and clinical data for identifying adults with undiagnosed diabetes and dysglycemia in Saudi Arabia. RESEARCH DESIGN AND METHODS: Data from 1,485 nonpregnant Saudi adults >=20 years of age without a current diagnosis of diabetes were obtained from urban and rural primary healthcare centers in 2009. Clinical and demographic data were obtained through physician-administered interviews. Oral glucose tolerance test data were used to define diabetes (fasting plasma glucose >=7.0 mmol/L or 2-h post-load glucose >=11.1 mmol/L) and dysglycemia (fasting plasma glucose >=5.6 mmol/L or 2-h post load glucose >=7.8 mmol/L). Predictive models were developed using data from 1,435 individuals. Multivariable logistic regression and receiver operating characteristic curves were used to develop and evaluate a separate risk score for both diabetes and dysglycemia. Scores were validated on a hold-out sample of 50 individuals. RESULTS: The risk score for undiagnosed diabetes contained age, history of gestational diabetes, smoking, family history of diabetes, and central obesity with a sensitivity of 76.6% and a specificity of 52.1%. The dysglycemia risk score contained age, gestational diabetes, hypertension, and central obesity with a sensitivity of 71.2% and a specificity of 54.0%. All performed equally well, if not better, in the hold-out sample. CONCLUSIONS: These risk scores can identify Saudi adults with undiagnosed diabetes or dysglycemia and should be validated in prospective studies. PMID- 26154414 TI - A Case-Crossover Study of Temperature and Infant Mortality in California. AB - BACKGROUND: While most research on temperature and mortality has focused on the elderly, little has concentrated on infants, who may also lack thermoregulatory responses to heat exposure. METHODS: We examined mean daily apparent temperature, a combination of temperature and humidity, and infant deaths in California during the warm season of May through October 1999 to 2011. Deaths from all causes and specifically from congenital malformations, sudden infant death syndrome, abnormal gestation duration, respiratory causes, and circulatory causes were considered in a time-stratified case-crossover analysis of 12 356 infant deaths. RESULTS: For all-cause mortality, excess risk was 4.4% (95% confidence interval 0.3, 9.2) per 5.6 degrees C increase for average of same day and previous 3 days apparent temperature (lag 03). The associations for apparent temperature and both all-cause mortality and deaths caused by gestation duration were highest for Black infants (13.3%, 95% CI 0.6, 27.6 and 23.7%, 95% CI -3.3, 58.2, respectively), while White infants had elevated risk for deaths from respiratory causes (44.6%; -0.7, 110.5). We further observed differential effects for neonates (infants aged 28 days and under) and post-neonates (infants above 28 days and under 1 year), and coastal and non-coastal regions. These associations remained even after considering criteria air pollutants. CONCLUSIONS: This study suggests that infants are a vulnerable subgroup to heat exposure. Further studies should be conducted with a sufficient number of cases of infant deaths in other locales. PMID- 26154415 TI - An Ion Gel as a Low-Cost, Spin-Coatable, High-Capacitance Dielectric for Electrowetting-on-Dielectric (EWOD). AB - For many practical electrowetting-on-dielectric (EWOD) applications, the use of high-capacitance dielectric materials is critically demanded to induce a large surface tension modulation. Thin-film dielectric layers such as Parylene C, silicon dioxide (SiO2), and aluminum oxide (Al2O3) have been commonly used for EWOD. However, these dielectric materials are fabricated by conventional integrated circuit (IC) processes which are typically time-consuming and require complex and expensive laboratory setups such as high-vacuum facilities. In this article, a novel ion gel material was demonstrated as a spin-coatable and high capacitance dielectric for low-cost EWOD applications. The ion gel offers a 2 or 3 order higher capacitance (c ~ 10 MUF/cm(2)) than conventional dielectrics commonly used for EWOD while being fabricated through a simple low-cost spin coating process. We discuss the fundamentals of an ion gel dielectric, its fabrication process of spin coating, and the interaction with a hydrophobic layer for practical EWOD applications. The ion gel films, which consist of a copolymer, poly(vinylidene fluoride-co-hexafluoropropylene) [P(VDF-HFP)], and an ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [EMIM][TFSI], were successfully deposited on ITO substrates by using a simple spin-coating process. The experimental demonstrations validated the theoretical modeling of the ion gel layer as a high-capacitance dielectric. The EWOD performance of the ion gel samples was compared to that of other conventional dielectric materials to show the performance improvement. PMID- 26154416 TI - Poly (3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) hydrogel promotes angiogenesis and collagen deposition during cutaneous wound healing in rats. AB - Wound management and healing in several physiological or pathological conditions, particularly when comorbidities are involved, usually proves to be difficult. This presents complications leading to socio-economic and public health burdens. The accelerative wound healing potential of biocompatible poly(3 hydroxyalkanoates)-co-(6-hydroxyhexanoate) (PHA-PCL) composite hydrogel is reported herein. The biosynthesized PHA-PCL macromer was cross-linked with PEGMA to give a hydrogel. Twenty-four rats weighing 200-250 g each were randomly assigned to four groups of six rats. Rats in group I (negative control) were dressed with sterilized gum acacia paste in 10% normal saline while PEGMA-alone hydrogel (PH) was used to dress group II (secondary control) rats. Group III rats were dressed with PHAs-PCL cross-linked PEGMA hydrogel (PPH). For the positive control (group IV), the rats were dressed with Intrasite((r)) gel. Biochemical, histomorphometric and immunohistomorphometric analyses revealed a significant difference in area closure and re-epithelialization on days 7 and 14 in PPH or Intrasite((r)) gel groups compared to gum acacia or PEGMA-alone groups. Furthermore, wounds dressed with PPH or Intrasite((r)) gel showed evident collagen deposition, enhanced fibrosis and extensively organized angiogenesis on day 14 compared to the negative control group. While improvement in wound healing of the PH dressed group could be observed, there was no significant difference between the negative control group and the PH dressed group in any of the tests. The findings suggested that topical application of PPH accelerated the rats' wound healing process by improving angiogenesis attributed to the increased microvessel density (MVD) and expressions of VEGF-A in tissue samples. Thus, PPH has been demonstrated to be effective in the treatment of cutaneous wounds in rats, and could be a potential novel agent in the management and acceleration of wound healing in humans and animals. PMID- 26154417 TI - Human Genome Editing and Ethical Considerations. AB - Editing human germline genes may act as boon in some genetic and other disorders. Recent editing of the genome of the human embryo with the CRISPR/Cas9 editing tool generated a debate amongst top scientists of the world for the ethical considerations regarding its effect on the future generations. It needs to be seen as to what transformation human gene editing brings to humankind in the times to come. PMID- 26154418 TI - Six Challenges for Ethical Conduct in Science. AB - The realities of human agency and decision making pose serious challenges for research ethics. This article explores six major challenges that require more attention in the ethics education of students and scientists and in the research on ethical conduct in science. The first of them is the routinization of action, which makes the detection of ethical issues difficult. The social governance of action creates ethical problems related to power. The heuristic nature of human decision making implies the risk of ethical bias. The moral disengagement mechanisms represent a human tendency to evade personal responsibility. The greatest challenge of all might be the situational variation in people's ethical behaviour. Even minor situational factors have a surprisingly strong influence on our actions. Furthermore, finally, the nature of ethics itself also causes problems: instead of clear answers, we receive a multitude of theories and intuitions that may sometimes be contradictory. All these features of action and ethics represent significant risks for ethical conduct in science. I claim that they have to be managed within the everyday practices of science and addressed explicitly in research ethics education. I analyse them and suggest some ways in which their risks can be alleviated. PMID- 26154419 TI - Dedicated Education Unit Model in a Hospice and Palliative Care Setting. AB - This article describes adapting the dedicated education unit model to the hospice/palliative care setting. The purpose of this qualitative study was to demonstrate how this unique academic service model helps to address the void that exists in hospice and palliative care in the clinical education of prelicensure nursing students. PMID- 26154420 TI - Quantitative Redox Imaging Software. AB - SIGNIFICANCE: A wealth of fluorescent reporters and imaging systems are now available to characterize dynamic physiological processes in living cells with high spatiotemporal resolution. The most reliable probes for quantitative measurements show shifts in their excitation or emission spectrum, rather than just a change in intensity, as spectral shifts are independent of optical path length, illumination intensity, probe concentration, and photobleaching, and they can be easily determined by ratiometric measurements at two wavelengths. RECENT ADVANCES: A number of ratiometric fluorescent reporters, such as reduction oxidation-sensitive green fluorescent protein (roGFP), have been developed that respond to the glutathione redox potential and allow redox imaging in vivo. roGFP and its derivatives can be expressed in the cytoplasm or targeted to different organelles, giving fine control of measurements from sub-cellular compartments. Furthermore, roGFP can be imaged with probes for other physiological parameters, such as reactive oxygen species or mitochondrial membrane potential, to give multi-channel, multi-dimensional 4D (x,y,z,t) images. CRITICAL ISSUES: Live cell imaging approaches are needed to capture transient or highly spatially localized physiological behavior from intact, living specimens, which are often not accessible by other biochemical or genetic means. FUTURE DIRECTIONS: The next challenge is to be able to extract useful data rapidly from such large (GByte) images with due care given to the assumptions used during image processing. This article describes a suite of software programs, available for download, that provide intuitive user interfaces to conduct multi-channel ratio imaging, or alternative analysis methods such as pixel-population statistics or image segmentation and object-based ratio analysis. Antioxid. Redox Signal. 24, 752 762. PMID- 26154422 TI - Impact of Gap Junctional Intercellular Communication on MLO-Y4 Sclerostin and Soluble Factor Expression. AB - Bone remodeling is a continual process in which old bone is resorbed by osteoclasts and new bone is formed by osteoblasts, providing a mechanism for bones' ability to adapt to changes in its mechanical environment. While the role of osteoblasts and osteoclasts in bone remodeling is well understood, the cellular regulation of bone remodeling is unclear. One theory is that osteocytes, found within bone, play an important role in controlling the bone remodeling response. Osteocytes possess gap junctions, narrow channels that extend between nearby cells and allow communication between cells via the transfer of small molecules and ions. This work investigated the potential role of gap junctional intercellular communication in bone remodeling by exposing osteocyte-like MLO-Y4 cells to mechanical strains and quantifying the expression of soluble factors, including sclerostin, a protein closely associated with bone remodeling. The soluble factors and sclerostin expression were further examined after inhibiting gap junctional intercellular communication to study the impact of the communication. At supraphysiologic strains, the inhibition of gap junctional intercellular communication led to increases in sclerostin expression relative to cells in which communication was present, indicating that the communication may play a significant role in regulating bone remodeling. PMID- 26154421 TI - A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice. AB - BACKGROUND: Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). METHODOLOGY: Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 MUg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization. PRINCIPLE FINDINGS: Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 MUg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model. CONCLUSION: We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens. PMID- 26154424 TI - A Case of Dominant Dystrophic Epidermolysis Bullosa Responding Well to an Old Medication. PMID- 26154426 TI - Early discharge with home support of gavage feeding for stable preterm infants who have not established full oral feeds. AB - BACKGROUND: Early discharge of stable preterm infants still requiring gavage feeds offers the benefits of uniting families sooner and reducing healthcare and family costs compared with discharge home when on full sucking feeds. Potential disadvantages of early discharge include increased care burden for the family and risk of complications related to gavage feeding. OBJECTIVES: To determine the effects of a policy of early discharge of stable preterm infants with home support of gavage feeding compared with a policy of discharge of such infants when they have reached full sucking feeds.We planned subgroup analyses to determine whether safety and efficacy outcomes are altered by the type of support received (outpatient visits vs home support) or by the maturity of the infants discharged (gestational age <= 28 weeks at birth or birth weight <= 1000 grams). SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group, together with searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to March 2015), EMBASE (1980 to March 2015) and MEDLINE (1950 to March 2015). We found no new trials. SELECTION CRITERIA: We included all randomised and quasi-randomised trials among infants born at < 37 weeks and requiring no intravenous nutrition at the point of discharge. Trials were required to compare early discharge home with gavage feeds and healthcare support versus later discharge home when full sucking feeds were attained. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We conducted study authors for additional information. We performed data analysis in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: We included in the review data from one quasi-randomised trial with 88 infants from 75 families. Infants in the early discharge programme with home gavage feeding had a mean hospital stay that was 9.3 days shorter (mean difference (MD) -9.3, 95% confidence interval (CI) -18.49 to -0.11) than that of infants in the control group. Infants in the early discharge programme also had lower risk of clinical infection during the home gavage period compared with those in the control group spending corresponding time in hospital (risk ratio 0.35, 95% CI 0.17 to 0.69). No significant differences were noted between groups in duration and extent of breast feeding, weight gain, re-admission within the first 12 months post discharge from the home gavage programme or from hospital, scores reflecting parental satisfaction or overall health service use. AUTHORS' CONCLUSIONS: Experimental evidence on the benefits and risks for preterm infants of early discharge from hospital with home gavage feeding compared with later discharge upon attainment of full sucking feeds is limited to the results of one small quasi-randomised controlled trial. High-quality trials with concealed allocation, complete follow-up of all randomly assigned infants and adequate sample size are needed before practice recommendations can be made. PMID- 26154425 TI - Systemic siRNA Nanoparticle-Based Drugs Combined with Radiofrequency Ablation for Cancer Therapy. AB - PURPOSE: Radiofrequency thermal ablation (RFA) of hepatic and renal tumors can be accompanied by non-desired tumorigenesis in residual, untreated tumor. Here, we studied the use of micelle-encapsulated siRNA to suppress IL-6-mediated local and systemic secondary effects of RFA. METHODS: We compared standardized hepatic or renal RFA (laparotomy, 1 cm active tip at 70 +/- 2 degrees C for 5 min) and sham procedures without and with administration of 150 nm micelle-like nanoparticle (MNP) anti-IL6 siRNA (DOPE-PEI conjugates, single IP dose 15 min post-RFA, C57Bl mouse:3.5 ug/100ml, Fisher 344 rat: 20 ug/200 ul), RFA/scrambled siRNA, and RFA/empty MNPs. Outcome measures included: local periablational cellular infiltration (alpha-SMA+ stellate cells), regional hepatocyte proliferation, serum/tissue IL-6 and VEGF levels at 6-72 hr, and distant tumor growth, tumor proliferation (Ki-67) and microvascular density (MVD, CD34) in subcutaneous R3230 and MATBIII breast adenocarcinoma models at 7 days. RESULTS: For liver RFA, adjuvant MNP anti-IL6 siRNA reduced RFA-induced increases in tissue IL-6 levels, alpha-SMA+ stellate cell infiltration, and regional hepatocyte proliferation to baseline (p < 0.04, all comparisons). Moreover, adjuvant MNP anti-IL6- siRNA suppressed increased distant tumor growth and Ki-67 observed in R3230 and MATBIII tumors post hepatic RFA (p<0.01). Anti-IL6 siRNA also reduced RFA-induced elevation in VEGF and tumor MVD (p < 0.01). Likewise, renal RFA-induced increases in serum IL-6 levels and distant R3230 tumor growth was suppressed with anti-IL6 siRNA (p < 0.01). CONCLUSIONS: Adjuvant nanoparticle-encapsulated siRNA against IL-6 can be used to modulate local and regional effects of hepatic RFA to block potential unwanted pro-oncogenic effects of hepatic or renal RFA on distant tumor. PMID- 26154427 TI - Acute pancreatitis. AB - PURPOSE OF REVIEW: To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. RECENT FINDINGS: Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. SUMMARY: The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality. PMID- 26154428 TI - Pancreatic pain. AB - PURPOSE OF REVIEW: Pain is the most common symptom of chronic pancreatitis, with a profound socioeconomic impact. Historical management paradigms failed, as they did not adequately address the fundamental underlying mechanisms. The present article describes the neurobiology of pain and sensitization in this condition, in an effort to explain prior failings and provide future directions for managing pain in chronic pancreatitis. RECENT FINDINGS: A number of recent advances have been made in understanding the neurobiology of pain for this condition. This has been coupled with clinical advances in assessing sensitization to pain in these patients, which has been shown to predict response to medical and surgical therapy. SUMMARY: Pain in chronic pancreatitis is complex. Addressing the mechanical and morphological findings in chronic pancreatitis without addressing the underlying neurobiological mechanisms is destined to fail. New advances in our understanding of the neurobiology of pain in chronic pancreatitis helps to explain prior failings and provides future direction for managing pain in patients afflicted by this disease. PMID- 26154429 TI - Recent developments in steroid-responsive pancreatitides (autoimmune pancreatitis). AB - PURPOSE OF REVIEW: There are two distinct steroid responsive chronic fibro inflammatory diseases of the pancreas, called type 1 and type 2 autoimmune pancreatitis (AIP). We review recent progress in this field. RECENT FINDINGS: It has recently been suggested that the term AIP be used to describe type 1 AIP and the term idiopathic duct-centric chronic pancreatitis (IDCP) be used for type 2 AIP. Clinical features and long-term outcomes of AIP and IDCP are well characterized and prognosis of both diseases is excellent. Diagnostic strategies tailored to regional practice patterns have emerged with the application of International Consensus Diagnostic Criteria for AIP. Although corticosteroids remain the mainstay of treatment, management of relapses and strategies for preventing multiple relapses are better understood, including the role of maintenance therapy and B-cell depletion therapy with rituximab. Association studies with malignancies have yielded conflicting results regarding risk of cancer in AIP. SUMMARY: The treatment, follow-up guidelines and associations continue to evolve with our increasing experience with both AIP and IDCP. In AIP, rituximab can be used for both induction and maintenance of remission. IDCP responds to steroids without need for maintenance therapy. Both AIP and IDCP have excellent prognosis. PMID- 26154430 TI - Primary endoscopic therapies for obesity and metabolic diseases. AB - PURPOSE OF REVIEW: Endoscopic approaches to obesity may help fulfill the unmet need of over half the US adult population who would benefit from therapy for obesity but are not receiving it. Endoluminal approaches have the potential to be more efficacious than antiobesity medications and have a lower risk-cost profile compared with bariatric surgery. This review outlines the current state of primary endoscopic weight loss and metabolic therapies and sheds light on the challenges faced toward making endoscopic bariatric therapies 'ready for prime time'. RECENT FINDINGS: Endoscopic approaches to obesity are being increasingly modeled on the proposed mechanisms contributing to the benefits of bariatric surgery.Therapies targeted at the stomach induce weight loss with only a proportional benefit to underlying metabolic disorders.Therapies targeting the proximal small bowel appear to modulate various neurohormonal pathways resulting in an improvement in metabolic profile in excess to that accounted for by weight loss itself. SUMMARY: Rigorous scientific assessment of endoscopic approaches to obesity is necessary to allow its integration into the treatment algorithm of obesity. The endoscopic armamentarium against obesity continues to evolve with the endoscopist poised to be a key player in the management of this disease. VIDEO ABSTRACT: http://links.lww.com/COG/A12. PMID- 26154431 TI - Prediction and Production of Simple Mathematical Equations: Evidence from Visual World Eye-Tracking. AB - The relationship between the production and the comprehension systems has recently become a topic of interest for many psycholinguists. It has been argued that these systems are tightly linked and in particular that listeners use the production system to predict upcoming content. In this study, we tested how similar production and prediction processes are in a novel version of the visual world paradigm. Dutch speaking participants (native speakers in Experiment 1; German-Dutch bilinguals in Experiment 2) listened to mathematical equations while looking at a clock face featuring the numbers 1 to 12. On alternating trials, they either heard a complete equation ("three plus eight is eleven") or they heard the first part ("three plus eight is") and had to produce the result ("eleven") themselves. Participants were encouraged to look at the relevant numbers throughout the trial. Their eye movements were recorded and analyzed. We found that the participants' eye movements in the two tasks were overall very similar. They fixated the first and second number of the equations shortly after they were mentioned, and fixated the result number well before they named it on production trials and well before the recorded speaker named it on comprehension trials. However, all fixation latencies were shorter on production than on comprehension trials. These findings suggest that the processes involved in planning to say a word and anticipating hearing a word are quite similar, but that people are more aroused or engaged when they intend to respond than when they merely listen to another person. PMID- 26154432 TI - Barriers to positive policy change that aims to increase access to medicines through reclassification: the case of oseltamivir in New Zealand. AB - OBJECTIVES: This study aims to identify and explore emergent barriers to consumers accessing oseltamivir without prescription following policy change introduced in New Zealand to increase access via community pharmacies. METHODS: Semi-structured interviews were conducted with 26 community pharmacists immediately following the first season of oseltamivir availability without prescription in October 2007. Interviews were transcribed verbatim and coded using a framework approach to identify themes. KEY FINDINGS: Non-prescription sales of oseltamivir were slow during this period. Participants acknowledged that they may have missed opportunities to recommend oseltamivir and attributed this to a range of reasons. Pharmacy-related barriers identified included limited pharmacist confidence, concerns about efficacy and safety of the product, location of the product in the pharmacy, affordability and the role of support staff. Many pharmacists adopted a 'risk-benefit analysis' that balanced symptom severity with perceived value for money. Consumer barriers included cost, limited awareness of availability and limited ability to correctly self-diagnose and manage influenza. CONCLUSIONS: Complexity in the factors that influenced pharmacist motivation to supply oseltamivir without prescription highlighted the potential for positive policy change to be hindered by multiple barriers. Greater understanding of such barriers is important for effective transition of medicines from prescription to non-prescription availability to achieve increased consumer access through reclassification. Concerns that pharmacists are influenced by commercial priorities when medicines are newly reclassified were not substantiated in this study. PMID- 26154433 TI - A New Look at Shelter 131/51 in the Natufian Site of Eynan (Ain-Mallaha), Israel. AB - In the past 25 years since the reconstruction of Shelter 131 of Eynan was suggested by Francois Valla, its image has become almost iconic--a highly cited symbol of early sedentism constituting a significant part of our knowledge on early stone constructions and the people behind them. A new look at the architectural remains and the stratigraphy resulted in an alternative reconstruction, essentially different than the one we have come to know. We used spatial (architectural-geometrical) analysis in order to study the relationships between the different architectural elements and to test our hypothesis that the series of postholes may have not pertained to the upper floor 131 of Layer IV as suggested by Perrot and Valla, but rather to the successive occupational and architectural episode. The association of the postholes with Wall 51 of Layer III sheds new light on the architectural remains revealing their geometric design, an important characteristic of Early Natufian Architecture, the meaning and implications of which we shortly discuss. PMID- 26154434 TI - Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG): toward integrated treatment of symptoms related to traumatic loss. AB - BACKGROUND: Traumatic events such as disasters, accidents, war, or criminal violence are often accompanied by the loss of loved ones, and may then give rise to traumatic grief. Traumatic grief refers to a clinical diagnosis of persistent complex bereavement disorder (PCBD) with comorbid (symptoms of) posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) following confrontation with a traumatic loss. Trauma survivors, who are frequently from different cultural backgrounds, have often experienced multiple losses and ambiguous loss (missing family members or friends). Current evidence-based treatments for PTSD do not focus on traumatic grief. OBJECTIVE: To develop a treatment for traumatic grief combining treatment interventions for PTSD and PCBD that may accommodate cultural aspects of grief. METHOD: To provide a rationale for treatment, we propose a cognitive stress model of traumatic grief. Based on this model and on existing evidence-based treatments for PTSD and complicated grief, we developed Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG) for the treatment of patients with traumatic grief. The treatment is presented along with a case vignette. RESULTS: Processes contributing to traumatic grief include inadequately integrating the memory of the traumatic loss, negative appraisal of the traumatic loss, sensitivity to matching triggers and new stressors, and attempting to avoid distress. BEP-TG targets these processes. The BEP-TG protocol consists of five parts with proven effectiveness in the treatment of PCBD, PTSD, and MDD: information and motivation, grief-focused exposure, memorabilia and writing assignments, finding meaning and activation, and a farewell ritual. CONCLUSION: Tailored to fit the needs of trauma survivors, BEP-TG can be used to address traumatic grief symptoms related to multiple losses and ambiguous loss, as well as cultural aspects of bereavement through its different components. PMID- 26154435 TI - Visualizing the Inner Architecture of Poly(epsilon-caprolactone)-Based Biomaterials and Its Impact on Performance Optimization. AB - The performance of poly(epsilon-caprolactone) (PCL)-based biomaterials is defined by spatial distributions of PCL's amorphous and crystalline domains. Unfortunately, directly visualizing their inner architectures has been challenging. This study demonstrates, the superior degradation selectivity of Candida antarctica lipase B (CALB) enzyme; when used at low concentrations, it preferentially breaks down the amorphous chains prior to the crystalline chains. Top-down dissection using this enzyme is performed on several PCL-based systems. Self-assembled nanolamellae (e.g., thin films) or hierarchically nanostructured crystalline skeletons (e.g., fibers) are clearly captured. Thus, the spatial distribution of the amorphous compartments can be precisely mapped out, which otherwise cannot be achieved. PMID- 26154436 TI - Effects of age, but not sex, on elevated startle during withdrawal from acute morphine in adolescent and adult rats. AB - Investigations into animal models of drug withdrawal have largely found that emotional signs of withdrawal (e.g. anxiety, anhedonia, and aversion) in adolescents are experienced earlier and less severely than in their adult counterparts. The majority of these reports have examined withdrawal from ethanol or nicotine. To expand our knowledge about the emotional withdrawal state in adolescent rats, we used potentiation of the acoustic startle reflex after an acute dose of morphine (10 mg/kg, subcutaneously) as a measure of opiate withdrawal. Startle was measured at four time points after morphine injection (2, 3, 4, and 5 h) in 28-day-old and 90-day-old male and female rats. The results of this experiment revealed that peak potentiation of the startle reflex occurred at 3 h in the adolescent rats and at 5 h in the adult rats, and that the magnitude of withdrawal was larger in the adults. No sex differences were observed. Overall, these results affirm that, similar to withdrawal from ethanol and nicotine, opiate withdrawal signs are less severe in adolescent than in adult rats. PMID- 26154437 TI - The antidepressant drugs fluoxetine and duloxetine produce anxiolytic-like effects in a schedule-induced polydipsia paradigm in rats: enhancement of fluoxetine's effects by the alpha2 adrenoceptor antagonist yohimbine. AB - Similar to the time-course for treating depression, several weeks of administration are required for serotonin (5-HT) reuptake inhibitors to produce anxiolytic effects. Previous studies with the schedule-induced polydipsia paradigm (a putative preclinical anxiety model) have shown that repeated administration of antidepressant drugs is necessary to produce a suppression of polydipsia, which is interpreted as an anxiolytic-like effect. The present study sought to expand past findings by evaluating the selective 5-HT reuptake inhibitor (SSRI) fluoxetine and the 5-HT-norepinephrine reuptake inhibitor duloxetine in the schedule-induced polydipsia paradigm with rats. Dose combinations of the alpha2 adrenoceptor antagonist yohimbine with fluoxetine were also explored to determine whether alpha2 adrenoceptor antagonism could enhance the anxiolytic-like effects produced by an SSRI. Fluoxetine and duloxetine significantly reduced water intake over the course of daily administrations. Daily treatment with the combination of fluoxetine and yohimbine produced a significantly greater reduction in water intake than fluoxetine alone. The present results confirmed previous findings that inhibition of 5-HT reuptake reduces water consumption in this paradigm. The results for the alpha2 antagonist yohimbine (in combination with fluoxetine) also indicate that alpha2 adrenoceptor antagonism may significantly enhance anxiolytic-like effects of SSRIs. PMID- 26154439 TI - Novel Blind Recognition Algorithm of Frame Synchronization Words Based on Soft Decision in Digital Communication Systems. AB - A novel blind recognition algorithm of frame synchronization words is proposed to recognize the frame synchronization words parameters in digital communication systems. In this paper, a blind recognition method of frame synchronization words based on the hard-decision is deduced in detail. And the standards of parameter recognition are given. Comparing with the blind recognition based on the hard decision, utilizing the soft-decision can improve the accuracy of blind recognition. Therefore, combining with the characteristics of Quadrature Phase Shift Keying (QPSK) signal, an improved blind recognition algorithm based on the soft-decision is proposed. Meanwhile, the improved algorithm can be extended to other signal modulation forms. Then, the complete blind recognition steps of the hard-decision algorithm and the soft-decision algorithm are given in detail. Finally, the simulation results show that both the hard-decision algorithm and the soft-decision algorithm can recognize the parameters of frame synchronization words blindly. What's more, the improved algorithm can enhance the accuracy of blind recognition obviously. PMID- 26154438 TI - Effects of the noncompetitive N-methyl-D-aspartate receptor antagonist ketamine on visual signal detection performance in rats. AB - The noncompetitive N-methyl-D-aspartate receptor antagonist ketamine produces consistent, rapid, and sustained antidepressant effects in patients suffering from treatment-resistant depression. However, ketamine-induced cognitive impairments remain a major concern. The present study sought to extend the preclinical evaluation of ketamine-induced cognitive impairments by evaluating the dose (1.0-18.0 mg/kg) and time-course (10 min-24 h) of effects of ketamine on sustained attention using a visual signal detection procedure in rats. Overall, ketamine (10.0-18.0 mg/kg) dose-dependently decreased percent hit and correct rejection accuracy. Additionally, these same doses of ketamine increased response latency and trial omissions. In the time-course study, treatment with 18.0 mg/kg ketamine produced the greatest decrease in visual signal detection performance at 10 min, when ketamine decreased percent hit and correct rejection accuracy as well as increased response latency and trial omissions, but returned to saline baseline controls by 100 min. In conclusion, acute ketamine inhibited sustained attention in rats performing a visual signal detection task; however, these effects were short in duration, similar to the short duration (<2 h) of psychotomimetic effects reported in low-dose ketamine treatment in depressed patients. PMID- 26154440 TI - Symmetry Engineering of Graphene Plasmonic Crystals. AB - The dispersion relation of plasmons in graphene with a periodic lattice of apertures takes a band structure. Light incident on this plasmonic crystal excites only particular plasmonic modes in select bands. The selection rule is not only frequency/wavevector matching but also symmetry matching, where the symmetry of plasmonic modes originates from the point group symmetry of the lattice. We demonstrate versatile manipulation of light-plasmon coupling behaviors by engineering the symmetry of the graphene plasmonic crystal. PMID- 26154441 TI - Transcatheter pulmonary embolectomy after fontan. AB - Pulmonary embolism (PE) is a significant cause of morbidity and mortality among hospitalized patients, and thrombolytics are the mainstay of treatment. However, for patients who fail or have contraindications to thrombolytic therapy, catheter based therapies, such as the AngioVac aspiration system, have emerged as an alternative to surgical embolectomy. Here, we present the novel case of a 22 year old woman with Fontan circulation who developed severe postpartum cardiomyopathy and a saddle PE. She failed thrombolytic therapy but underwent successful pulmonary embolectomy by AngioVac aspiration. Patients with Fontan circulation have an increased incidence of thromboembolic events, and AngioVac thrombectomy is a valuable treatment option in these complex patients. PMID- 26154442 TI - Comparison between magnetic resonance imaging and computed tomography of the lung in patients with cystic fibrosis with regard to clinical, laboratory, and pulmonary functional parameters. AB - OBJECTIVE: To evaluate whether magnetic resonance imaging (MRI) is effective as computed tomography (CT) in determining morphologic and functional pulmonary changes in patients with cystic fibrosis (CF) in association with multiple clinical parameters. MATERIALS AND METHODS: Institutional review board approval and patient written informed consent were obtained. In this prospective study, 30 patients with CF (17 men and 13 women; mean (SD) age, 30.2 (9.2) years; range, 19 52 years) were included. Chest CT was acquired by unenhanced low-dose technique for clinical purposes. Lung MRI (1.5 T) comprised T2- and T1-weighted sequences before and after the application of 0.1-mmol.kg gadobutrol, also considering lung perfusion imaging. All CT and MR images were visually evaluated by using 2 different scoring systems: the modified Helbich and the Eichinger scores. Signal intensity of the peribronchial walls and detected mucus on T2-weighted images as well as signal enhancement of the peribronchial walls on contrast-enhanced T1 weighted sequences were additionally assessed on MRI. For the clinical evaluation, the pulmonary exacerbation rate, laboratory, and pulmonary functional parameters were determined. RESULTS: The overall modified Helbich CT score had a mean (SD) of 15.3 (4.8) (range, 3-21) and median of 16.0 (interquartile range [IQR], 6.3). The overall modified Helbich MR score showed slightly, not significantly, lower values (Wilcoxon rank sum test and Student t test; P > 0.05): mean (SD) of 14.3 (4.7) (range, 3-20) and median of 15.0 (IQR, 7.3). Without assessment of perfusion, the overall Eichinger score resulted in the following values for CT vs MR examinations: mean (SD), 20.3 (7.2) (range, 4-31); and median, 21.0 (IQR, 9.5) vs mean (SD), 19.5 (7.1) (range, 4-33); and median, 20.0 (IQR, 9.0). All differences between CT and MR examinations were not significant (Wilcoxon rank sum tests and Student t tests; P > 0.05). In general, the correlations of the CT scores (overall and different imaging parameters) to the clinical parameters were slightly higher compared to the MRI scores. However, if all additional MRI parameters were integrated into the scoring systems, the correlations reached the values of the CT scores. The overall image quality was significantly higher for the CT examinations compared to the MRI sequences. CONCLUSIONS: One major diagnostic benefit of lung MRI in CF is the possible acquisition of several different morphologic and functional imaging features without the use of any radiation exposure. Lung MRI shows reliable associations with CT and clinical parameters, which suggests its implementation in CF for routine diagnosis, which would be particularly important in follow-up imaging over the long term. PMID- 26154443 TI - Facet-dependent NiS2 polyhedrons on counter electrodes for dye-sensitized solar cells. AB - Octahedral and cubic NiS2 nanocrystals enclosed by {111} and {100} planes were separately used as counter electrodes (CEs) incorporated into Pt-free dye sensitized solar cells (DSSCs). The DSSC assembled by NiS2 octahedrons exhibited a conversion efficiency of 5.98%, better than that by NiS2 cubes (5.43%). DFT calculations indicate that the better catalytic effect could be ascribed to higher surface energy, more active sites, and more suitable adsorption energy of {111} planes compared with the {100} planes. PMID- 26154444 TI - Importance of the Hispanic heritage regarding diagnosis and management of hypertension. AB - Hypertension (HTN) is a very prevalent and growing clinical problem that is not always promptly diagnosed and ~6% of U.S. adults remain undiagnosed. Though numerous risk factors have been linked to the development of HTN, ethnicity has traditionally been simply considered as a significant risk among non-Hispanic Blacks. However, emerging data seems to suggest that Hispanics, the largest and fastest-growing minority in the U.S.A., might have rates of uncontrolled HTN that significantly exceeds the rates observed for non-Hispanic whites. Unfortunately, paucity of a significant Hispanic representation in major clinical trials has raised significant healthcare concerns regarding our true understanding of the meaning of HTN and associated cardiovascular consequences among this ethnic group. Consequently, there is urgency not only in having a better understanding of HTN among Hispanics, but also to examine the potential factors that may play a role in regulating the expression of HTN and its associated cardiovascular manifestations in this ethnic group. PMID- 26154445 TI - How to protect incompetent clinical research subjects involved in critical care or emergency settings. AB - Clinical research is an essential component of medical activity, and this is also true in intensive care. Adequate information and consent are universally considered necessary for the protection of research subjects. However, in emergency situations, the majority of critical patients are unable to consent and a valid legal representative is often unavailable. The situation is even more complex in Italy, where the relevant legislation fails to specify how investigators should manage research in emergency or critical care setting when it involves incompetent patients who do not have an appointed legal representative. While special measures for the protection of incompetent subjects during emergency research are necessary, not allowing such research at all dooms critically ill patients to receive non-evidence-based treatments without the prospect of improvement. The recently-issued EU Regulation n. 536/2014 will probably help shed light on this situation. Indeed, it specifically addresses the issue of "research in emergency situations" and introduces detailed rules aimed at protecting patients while allowing research. In this article, we argue that obtaining informed consent during emergency research on incompetent subjects in unrealistic, and that in most cases substituted judgment on the part of a proxy carries major flaws. Strict criteria in evaluating the risk-benefit ratio of proposed intervention and a careful evaluation of the trial by a local or national Research Ethics Committee are perhaps the most practicable solution. PMID- 26154446 TI - Time course of cytokines, hemodynamic and metabolic parameters during hyperthermic intraperitoneal chemotherapy. AB - INTRODUCTION: Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters. MATERIAL AND METHODS: Pre-, Intra- and Post operative data were collected. Tumor necrosis factor (TNF), interleukine 6, procalcitonine (PCT), cancer antigen 125 (CA-125) in blood and in peritoneal fluids were evaluated. RESULTS: Thirty-eight patients included, 29 (76.3%) female. Mean/median PCI: 9.2/5. Primary malignancy: 5 colo-rectal (13.2%), 5 gastric (13.2%), 23 ovarian (60.5%) and 5 others (13.2%). CCR 0-1 reached in all patients. Cardiac Index, Heart rate and Central Venous Pressure, increased during the procedure while Stroke Volume Variation showed a decrease. Mean Arterial Pressure and Superior Vena Cava Oxygenation were stable through the whole procedure. TNF and CA-125 were steady during the whole procedure; IL-6 had a relevant increase from baseline to start of perfusion (p<0.01); PCT had a steady increase at every time point. Peritoneal sampling showed a statistically significant increase (p<0.01) between start and end of the perfusion phase for all markers but TNF. Serum and peritoneal marker concentration were similar for TNF, PCT and CA-125. IL-6 showed a sharp difference. CONCLUSION: The most significant variations are those of IL-6 and PCT. The cytokines level parallel the hemodynamic derangements. Treatment during HIPEC should mimic the established treatment during sepsis and septic shock. PMID- 26154447 TI - Setting Up an Efficient Therapeutic Hypothermia Team in Conscious ST Elevation Myocardial Infarction Patients: A UK Heart Attack Center Experience. AB - Patients presenting with ST elevation myocardial infarction (STEMI) are routinely treated with percutaneous coronary intervention to restore blood flow in the occluded artery to reduce infarct size (IS). However, there is evidence to suggest that the restoration of blood flow can cause further damage to the myocardium through reperfusion injury (RI). Recent research in this area has focused on minimizing damage to the myocardium caused by RI. Therapeutic hypothermia (TH) has been shown to be beneficial in animal models of coronary artery occlusion in reducing IS caused by RI if instituted early in an ischemic myocardium. Data in humans are less convincing to date, although exploratory analyses suggest that there is significant clinical benefit in reducing IS if TH can be administered at the earliest recognition of ischemia in anterior myocardial infarction. The Essex Cardiothoracic Centre is the first UK center to have participated in administering TH in conscious patients presenting with STEMI as part of the COOL-AMI case series study. In this article, we outline our experience of efficiently integrating conscious TH into our primary percutaneous intervention program to achieve 18 minutes of cooling duration before reperfusion, with no significant increase in door-to-balloon times, in the setting of the clinical trial. PMID- 26154448 TI - The importance of distribution-choice in modeling substance use data: a comparison of negative binomial, beta binomial, and zero-inflated distributions. AB - BACKGROUND: It is important to correctly understand the associations among addiction to multiple drugs and between co-occurring substance use and psychiatric disorders. Substance-specific outcomes (e.g. number of days used cannabis) have distributional characteristics which range widely depending on the substance and the sample being evaluated. OBJECTIVES: We recommend a four-part strategy for determining the appropriate distribution for modeling substance use data. We demonstrate this strategy by comparing the model fit and resulting inferences from applying four different distributions to model use of substances that range greatly in the prevalence and frequency of their use. METHODS: Using Timeline Followback (TLFB) data from a previously-published study, we used negative binomial, beta-binomial and their zero-inflated counterparts to model proportion of days during treatment of cannabis, cigarettes, alcohol, and opioid use. The fit for each distribution was evaluated with statistical model selection criteria, visual plots and a comparison of the resulting inferences. RESULTS: We demonstrate the feasibility and utility of modeling each substance individually and show that no single distribution provides the best fit for all substances. Inferences regarding use of each substance and associations with important clinical variables were not consistent across models and differed by substance. CONCLUSION: Thus, the distribution chosen for modeling substance use must be carefully selected and evaluated because it may impact the resulting conclusions. Furthermore, the common procedure of aggregating use across different substances may not be ideal. PMID- 26154449 TI - Evolutionary History of Atmospheric CO2 during the Late Cenozoic from Fossilized Metasequoia Needles. AB - The change in ancient atmospheric CO2 concentrations provides important clues for understanding the relationship between the atmospheric CO2 concentration and global temperature. However, the lack of CO2 evolution curves estimated from a single terrestrial proxy prevents the understanding of climatic and environmental impacts due to variations in data. Thus, based on the stomatal index of fossilized Metasequoia needles, we reconstructed a history of atmospheric CO2 concentrations from middle Miocene to late Early Pleistocene when the climate changed dramatically. According to this research, atmospheric CO2 concentration was stabile around 330-350 ppmv in the middle and late Miocene, then it decreased to 278-284 ppmv during the Late Pliocene and to 277-279 ppmv during the Early Pleistocene, which was almost the same range as in preindustrial time. According to former research, this is a time when global temperature decreased sharply. Our results also indicated that from middle Miocene to Pleistocene, global CO2 level decreased by more than 50 ppmv, which may suggest that CO2 decrease and temperature decrease are coupled. PMID- 26154450 TI - How much is it worth a smile? PMID- 26154451 TI - CONSORT: when and how to use it. PMID- 26154452 TI - An interview with Matheus Melo Pithon. PMID- 26154453 TI - Radiographic evaluation of orthodontic treatment by means of four different cephalometric superimposition methods. AB - INTRODUCTION: Despite discussion on the merit of various cephalometric superimposition methods, there remains a need to assess which one can be used in daily practice with reasonably accuracy and less working time. OBJECTIVE: The aim of this study was to investigate four methods of cephalometric superimposition by means of assessing the longitudinal changes in craniofacial morphology caused by growth and response of adolescents with Class I malocclusion to orthodontic treatment involving first premolar extraction. METHODS: Pretreatment (T1) and post-treatment (T2) standardized lateral cephalometric radiographs of 31 adolescents (20 females and 11 males), with Angle Class I malocclusion and indication of premolar extraction, participated in this study. Radiographs were digitized, traced and had structures identified by means of a cephalometric software. Four superimposition methods were used: Bjork structural method, Steiner/Tweed SN line, Ricketts N-Ba line at N-point and Ricketts N-Ba line at CC point. Positional changes were quantified by horizontal and vertical linear changes in the following cephalometric landmarks: anterior/posterior nasal spine (ANS and PNS), gnathion (Gn), Gonion (Go), Pogonion (Pog), A-point and B-point. Differences between T1 and T2 in horizontal and vertical positional changes for all superimposition methods were assessed by one-way analysis of variance (ANOVA) and Bonferroni correction (p < 0.05). RESULTS: There were no statistically significant differences among the cephalometric superimposition methods or when patients' sex was considered. CONCLUSION: Bjork structural method, Steiner/Tweed SN line, Ricketts N-Ba line at N-point and Ricketts N-Ba line at CC-point methods were reliable and presented similar precision when the overall facial changes due to active growth and/or orthodontic treatment were examined. PMID- 26154454 TI - Low-level laser therapy effects on pain perception related to the use of orthodontic elastomeric separators. AB - INTRODUCTION: Some patients refer to pre-banding orthodontic separation as a painful orthodontic procedure. Low-level laser therapy (LLLT) has been reported to have local analgesic effect. OBJECTIVE: The aim of this single-blind study was to investigate the perception of pain caused by orthodontic elastomeric separators with and without a single LLLT application (6J). METHODS: The sample comprised 79 individuals aged between 13 and 34 years old at orthodontic treatment onset. Elastomeric separators were placed in first maxillary molars at mesial and distal surfaces and kept in place for three days. The volunteers scored pain intensity on a visual analogue scale (VAS) after 6 and 12 hours, and after the first, second and third days. One third of patients received laser applications, whereas another third received placebo applications and the remaining ones were controls. Applications were performed in a split-mouth design. Thus, three groups (laser, placebo and control) were assessed. RESULTS: No differences were found among groups considering pain perception in all periods observed. CONCLUSION: The use of a single-dose of LLLT did not cause significant reduction in orthodontic pain perception. Overall pain perception due to orthodontic separator placement varied widely and was usually mild. PMID- 26154455 TI - Immediate impact of rapid maxillary expansion on upper airway dimensions and on the quality of life of mouth breathers. AB - OBJECTIVE: To assess short-term tomographic changes in the upper airway dimensions and quality of life of mouth breathers after rapid maxillary expansion (RME). METHODS: A total of 25 mouth breathers with maxillary atresia and a mean age of 10.5 years old were assessed by means of cone-beam computed tomography (CBCT) and a standardized quality of life questionnaire answered by patients' parents/legal guardians before and immediately after rapid maxillary expansion. RESULTS: Rapid maxillary expansion resulted in similar and significant expansion in the width of anterior (2.8 mm, p < 0.001) and posterior nasal floor (2.8 mm, p < 0.001). Although nasopharynx and nasal cavities airway volumes significantly increased (+1646.1 mm3, p < 0.001), oropharynx volume increase was not statistically significant (+1450.6 mm3, p = 0.066). The results of the quality of life questionnaire indicated that soon after rapid maxillary expansion, patients' respiratory symptoms significantly decreased in relation to their initial respiratory conditions. CONCLUSIONS: It is suggested that RME produces significant dimensional increase in the nasal cavity and nasopharynx. Additionally, it also positively impacts the quality of life of mouth-breathing patients with maxillary atresia. PMID- 26154456 TI - Dentoalveolar mandibular changes with self-ligating versus conventional bracket systems: A CBCT and dental cast study. AB - OBJECTIVE: The aim of the present study was to compare dentoalveolar changes in mandibular arch, regarding transversal measures and buccal bone thickness, in patients undergoing the initial phase of orthodontic treatment with self-ligating or conventional bracket systems. METHODS: A sample of 25 patients requiring orthodontic treatment was assessed based on the bracket type. Group 1 comprised 13 patients bonded with 0.022-in self-ligating brackets (SLB). Group 2 included 12 patients bonded with 0.022-in conventional brackets (CLB). Cone-beam computed tomography (CBCT) scans and a 3D program (Dolphin) assessed changes in transversal width of buccal bone (TWBB) and buccal bone thickness (BBT) before (T1) and 7 months after treatment onset (T2). Measurements on dental casts were performed using a digital caliper. Differences between and within groups were analyzed by Student's t-test; Pearson correlation coefficient was also calculated. RESULTS: Significant mandibular expansion was observed for both groups; however, no significant differences were found between groups. There was significant decrease in mandibular buccal bone thickness and transversal width of buccal bone in both groups. There was no significant correlation between buccal bone thickness and dental arch expansion. CONCLUSIONS: There were no significant differences between self-ligating brackets and conventional brackets systems regarding mandibular arch expansion and changes in buccal bone thickness or transversal width of buccal bone. PMID- 26154457 TI - Periodontal and dental effects of surgically assisted rapid maxillary expansion, assessed by using digital study models. AB - OBJECTIVE: The present study assessed the maxillary dental arch changes produced by surgically assisted rapid maxillary expansion (SARME). METHODS: Dental casts from 18 patients (mean age of 23.3 years) were obtained at treatment onset (T1), three months after SARME (T2) and 6 months after expansion (T3). The casts were scanned in a 3D scanner (D-250, 3Shape, Copenhagen, Denmark). Maxillary dental arch width, dental crown tipping and height were measured and assessed by ANOVA and Tukey's test. RESULTS: Increased transversal widths from T1 and T2 and the maintenance of these values from T2 and T3 were observed. Buccal teeth tipping also showed statistically significant differences, with an increase in all teeth from T1 to T2 and a decrease from T2 to T3. No statistically significant difference was found for dental crown height, except for left first and second molars, although clinically irrelevant. CONCLUSION: SARME proved to be an effective and stable procedure, with minimum periodontal hazards. PMID- 26154458 TI - Changes in lower dental arch dimensions and tooth alignment in young adults without orthodontic treatment. AB - OBJECTIVE: The aim of this longitudinal study, comprising young adults without orthodontic treatment, was to assess spontaneous changes in lower dental arch alignment and dimensions. METHODS: Twenty pairs of dental casts of the lower arch, obtained at different time intervals, were compared. Dental casts obtained at T1 (mean age = 20.25) and T2 (mean age = 31.2) were compared by means of paired t-test (p < 0.05). RESULTS: There was significant reduction in arch dimensions: 0.43 mm for intercanine (p = 0.0089) and intermolar (p = 0.022) widths, and 1.28 mm for diagonal arch length (p < 0.001). There was a mild increase of approximately 1 mm in the irregularity index used to assess anterior alignment (p < 0.001). However, regression analysis showed that changes in the irregularity index revealed no statistically significant association with changes in the dental arch dimensions (p > 0.05). Furthermore, incisors irregularity at T2 could not be predicted due to the severity of this variable at T1 (p = 0.5051). CONCLUSION: Findings suggest that post-growth maturation of the lower dental arch leads to a reduction of dental arch dimensions as well as to a mild, yet significant, increase in dental crowding, even in individuals without orthodontic treatment. Furthermore, dental alignment in the third decade of life cannot be predicted based on the severity of dental crowding at the end of the second decade of life. PMID- 26154459 TI - Transdisciplinary treatment of Class III malocclusion using conventional implant supported anchorage: 10-year posttreatment follow-up. AB - INTRODUCTION: Combined treatment offers advantages for partially edentulous patients. Conventional implants, used as orthodontic anchorage, enable previous orthodontic movement, which provides appropriate space gain for crown insertion. OBJECTIVE: This case report describes the treatment of a 61-year and 10-month-old patient with negative overjet which made ideal prosthetic rehabilitation impossible, thereby hindering dental and facial esthetics. CASE REPORT: After a diagnostic setup, conventional implants were placed in the upper arch to anchor intrusion and retract anterior teeth. Space gain for lateral incisors was achieved in the lower arch by means of an orthodontic appliance. CONCLUSIONS: Integrated planning combining Orthodontics and Implantology provided successful treatment by means of conventional implant-supported anchorage. The resulting occlusal relationship proved stable after 10 years. PMID- 26154461 TI - Facial profile esthetic preferences: perception in two Brazilian states. AB - OBJECTIVE: The aim of this study was to assess the regional influence on the perception of facial profile esthetics in Rio de Janeiro state (RJ) and Rio Grande do Sul state (RS), Brazil. METHODS: Two Caucasian models, a man and a woman, with balanced facial profiles, had their photographs digitally manipulated so as to produce seven different profiles. First year dental students (laypeople) assessed the images and classified them according to their esthetic preference. RESULTS: The result of the t test for independent samples showed differences among states for certain facial profiles. The female photograph identified with the letter 'G' (mandibular retrusion) received higher scores in RS state (p = 0.006). No differences were found for male photographs (p > 0.007). The evaluators' sex seemed not to influence their esthetic perception (p > 0.007). Considering all evaluators together, ANOVA/Tukey's test showed differences among the profiles (p <= 0.05) for both male and female photographs. The female photograph that received the highest score was the one identified with the letter 'F' (dentoalveolar bimaxillary retrusion/ straight profile). For the male profiles, photograph identified with the letter 'E' (dentoalveolar bimaxillary protrusion/ straight profile) received the best score. CONCLUSION: Regional differences were observed regarding preferences of facial profile esthetics. In Rio de Janeiro state, more prominent lips were preferred while in Rio Grande do Sul state, profiles with straight lips were favored. Class III profiles were considered less attractive. PMID- 26154460 TI - Craniofacial changes and symptoms of sleep-disordered breathing in healthy children. AB - INTRODUCTION: The main cause of mouth breathing and sleep-disordered breathing (SDB) in childhood is associated with upper airway narrowing to varying degrees. OBJECTIVE: The aim of this study was to assess the prevalence of morphological and functional craniofacial changes and the main clinical symptoms of SDB in healthy children. METHODS: A cross-sectional observational study was conducted. A sample comprising 687 healthy schoolchildren, aged 7-12 years old and attending public schools, was assessed by medical history, clinical medical and dental examination, and respiratory tests. The self-perceived quality of life of mouth breathing children was obtained by a validated questionnaire. RESULTS: Out of the total sample, 520 children were nose breathers (NB) while 167 (24.3%) were mouth breathers (MB); 32.5% had severe hypertrophy of the palatine tonsils, 18% had a Mallampati score of III or IV, 26.1% had excessive overjet and 17.7% had anterior open bite malocclusion. Among the MB, 53.9% had atresic palate, 35.9% had lip incompetence, 33.5% reported sleepiness during the day, 32.2% often sneezed, 32.2% had a stuffy nose, 19.6% snored, and 9.4% reported having the feeling to stop breathing while asleep. However, the self-perception of their quality of life was considered good. CONCLUSION: High prevalence of facial changes as well as signs and symptoms of mouth breathing were found among health children, requiring early diagnosis and treatment to reduce the risk of SDB. PMID- 26154462 TI - Sterilizing elastomeric chains without losing mechanical properties. Is it possible? AB - OBJECTIVE: To investigate the effects of different sterilization/disinfection methods on the mechanical properties of orthodontic elastomeric chains. METHODS: Segments of elastomeric chains with 5 links each were sent for sterilization by cobalt 60 (Co60) (20 KGy) gamma ray technology. After the procedure, the elastomeric chains were contaminated with clinical samples of Streptococcus mutans. Subsequently, the elastomeric chains were submitted to sterilization/disinfection tests carried out by means of different methods, forming six study groups, as follows: Group 1 (control - without contamination), Group 2 (70 degrees GL alcohol), Group 3 (autoclave), Group 4 (ultraviolet), Group 5 (peracetic acid) and Group 6 (glutaraldehyde). After sterilization/disinfection, the effectiveness of these methods, by Colony forming units per mL (CFU/mL), and the mechanical properties of the material were assessed. Student's t-test was used to assess the number of CFUs while ANOVA and Tukey's test were used to assess elastic strength. RESULTS: Ultraviolet treatment was not completely effective for sterilization. No loss of mechanical properties occurred with the use of the different sterilization methods (p > 0.05). CONCLUSION: Biological control of elastomeric chains does not affect their mechanical properties. PMID- 26154463 TI - Treating dental crowding with mandibular incisor extraction in an Angle Class I patient. AB - Mandibular dental crowding often encourages patients to seek orthodontic treatment. The orthodontist should decide between protrusion of incisors or decrease in dental volume so as to achieve proper alignment and leveling. The present study reports the treatment of an Angle Class I malocclusion adolescent female brachyfacial patient with severe mandibular dental crowding, increased curve of Spee and deep overbite. The patient was treated with extraction of a mandibular incisor. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as a requirement for the title of certified by the BBO. PMID- 26154465 TI - Use of Gamma-Irradiated Cornea to Plug Sclerostomy Site During Tube Shunt Revision. AB - Tube shunt implantation is a common procedure for control of intraocular pressure (IOP). However, tube revision and repositioning must sometimes be performed, and this involves removing the tube from its sclerostomy site. This site is prone to leaking and this may cause postoperative hypotony. We describe a novel and cosmetically acceptable technique of plugging and covering the sclerostomy site with gamma-irradiated corneal tissue. PMID- 26154464 TI - Indirect orthodontic bonding--a modified technique for improved efficiency and precision. AB - INTRODUCTION: The indirect bonding technique optimizes fixed appliance installation at the orthodontic office, ensuring precise bracket positioning, among other advantages. In this laboratory clinical phase, material and methods employed in creating the transfer tray are decisive to accuracy. OBJECTIVE: This article describes a simple, efficient and reproducible indirect bonding technique that allows the procedure to be carried out successfully. Variables influencing the orthodontic bonding are analyzed and discussed in order to aid professionals wishing to adopt the indirect bonding technique routinely in their clinical practice. PMID- 26154466 TI - Magnetically modified microalgae and their applications. AB - The majority of algal cells can interact with a wide range of nano- and microparticles. Upon interaction the modified cells usually maintain their viability and the presence of foreign material on their surfaces or in protoplasm can provide additional functionalities. Magnetic modification and labeling of microalgal biomass ensures a wide spectrum of biotechnological, bioanalytical and environmental applications. Different aspects of microalgal cell magnetic modification are covered in the review, followed by successful applications of magnetic algae. Modified cells can be employed during their harvesting and removal, applied in toxicity microscreening devices and also as efficient adsorbents of different types of xenobiotics. PMID- 26154467 TI - The affect heuristic in occupational safety. AB - BACKGROUND: The affect heuristic is a rule of thumb according to which, in the process of making a judgment or decision, people use affect as a cue. If a stimulus elicits positive affect then risks associated to that stimulus are viewed as low and benefits as high; conversely, if the stimulus elicits negative affect, then risks are perceived as high and benefits as low. OBJECTIVES: The basic tenet of this study is that affect heuristic guides worker's judgment and decision making in a risk situation. The more the worker likes her/his organization the less she/he will perceive the risks as high. METHOD: A sample of 115 employers and 65 employees working in small family agricultural businesses completed a questionnaire measuring perceived safety costs, psychological safety climate, affective commitment and safety compliance. RESULTS: A multi-sample structural analysis supported the thesis that safety compliance can be explained through an affect-based heuristic reasoning, but only for employers. CONCLUSIONS: Positive affective commitment towards their family business reduced employers' compliance with safety procedures by increasing the perceived cost of implementing them. PMID- 26154468 TI - [In-depth assessment of work-related stress in a major company undergoing restructuring]. AB - BACKGROUND: An in-depth assessment of work-related stress was conducted in a major national telecommunications company undergoing major changes. The assessment was made on three homogeneous groups of workers and covered a large representative sample of the corresponding populations. OBJECTIVES: To identify the main sources of stress for the three populations of workers, stimulate a discussion on the possible corrective actions, and assess the impact of the on going organizational changes on workers' health. METHODS: The assessment started with an analysis of the objective stress indicators listed in the INAIL (National Insurance Institute for Occupational Diseases and Accidents) Checklist. This was followed by a combination of qualitative and quantitative investigations on work context and tasks and on the subjective perceptions of workers, which were carried out by using: semi-structured interviews with management, field observations of work tasks, focus groups and questionnaires (GHQ-12, HSE Indicator Tool, ad-hoc questionnaire). RESULTS: The assessment allowed identification of the critical areas to be addressed with specific interventions: relationship with the company, work performance, work organization, and equipment. CONCLUSIONS: the investigation allowed to identification of specific practical actions (improvement of technological tools; professional development through training courses) as well as strategic actions ( re-establish relationship of trust with the company) so as to mitigate the workers' level of stress. Analysis of the results also showed that the three targeted populations differed in the degree of acceptance and understanding of the organizational changes. PMID- 26154469 TI - [Accident prevention in agriculture in the ASL1 Abruzzo Local Health Service: protection facilities for tractors]. AB - BACKGROUND: The ASL1 workplace prevention and safety service in Abruzzo has been conducting workplace inspections on agricultural and livestock farms in the province of L'Aquila since 2011, mainly in the areas of Avezzano, Sulmona and L'Aquila. The agricultural sector in Abruzzo is characterized by high rates of accidents and the ratio of fatal injuries/total injuries is higher than the industry and services sector. OBJECTIVES: To evaluate the presence or absence of safety devices , i.e. compliance or otherwise with regulations for tractors, and of any variable factor that could be associated with the safety of the vehicle. METHODS: Between 2011 and 2013, 98 farms in the province of L'Aquila were inspected. The data resulting from the inspections was collected by the use of a checklist. An univariate logistic regression analysis was conducted in which the vehicles that complied with regulations were considered as the dependant variable, and the age of the tractor owner, the acres of worked land and the type of farm were considered as explanatory variables. Statistical elaboration was carried out using the Stata 12 programme. RESULTS: Out of a total of 298 tractors that were checked, 64.8% did not comply with regulations due to absence or unsuitability of one or more safety devices such as: a protective device in case of overturning; retention system of the driver; mounting and dismounting from the vehicle; protection of moving parts and hot parts; PTO (Power Take Off) protection device. A significant association between non-compliance of vehicles and the age of the owner and acres worked was observed, whereas no statistical significance was observed for the association with the farm type variable. CONCLUSION: Our study showed that farms where the owner's age is between 50 and 64 years and where more acres of land are worked are those where the agricultural or forestry tractors had lower levels of compliance with regulations. PMID- 26154470 TI - [Professional outcomes and psychological health after workplace bullying: an exploratory follow-up study]. AB - BACKGROUND: The literature shows that workplace bullying can lead to negative consequences for both individuals' health and professional outcomes. Most of these studies used cross-sectional designs and self-report questionnaires and further research is needed in order to explore long-term effects of workplace bullying. OBJECTIVES: This follow-up study aimed to explore professional and psychological outcomes in a sample of subjects who required a specialized and multidisciplinary assessment for psychological problems related, in their opinion, to workplace bullying. METHODS: The sample includes 71 patients with a baseline diagnosis of work-related psychological disorder who were assessed at follow-up by means of a structured telephone interview. The interview included structured questions about professional career developments and psycho-somatic health, and administration of the General Health Questionnaire-12. RESULTS: 62.0% of the participants were currently working and, of these, 59.1% had changed workplace after experiencing mobbing. Patients who changed workplace scored significantly higher on job satisfaction levels (p<0.01) and showed lower levels of social dysfunction (p<0.01) compared to those who did not change their job. Patients with a baseline diagnosis of Adjustment disorder/Post-Traumatic Stress disorder had higher levels of general dysphoria (p<0.04) and social dysfunction (p<0.01) at follow-up than other patients. CONCLUSIONS: These findings stress the importance of an accurate diagnostic assessment of mobbing-related psychopathological disorder. Victims of workplace bullying require early and continuous psychological support in order to promote their psychological well being and work reinstatement. PMID- 26154471 TI - [The role of information and training for workers on the correct use of earplugs in assessing real noise attenuation with E-A-RfitTM system]. AB - BACKGROUND: Laboratory levels of perceived noise attenuation as heard using earplugs are always higher than the real levels that can be achieved at the workplace. The employer is bound by law to supply individual hearing protection devices (HPDs), to assess their efficiency and efficacy, and also to inform and train workers on the correct use of HPDs. OBJECTIVES: This study assessed the real "personal attenuation rating" (PAR) of HPDs used by workers at the workplace, before (PAR A) and after (PAR B) specific and individual training. These values were also compared with the theoretical "single number rating" (SNR) provided by the manufacturer. METHODS: The study covered all the 65 male employees of an awnings factory, using the E-A-RfitTM computerized method, which can measure PARs, based on the difference between sound pressures recorded by an "outside" microphone and an "inside" microphone placed in the auditory canal, with earplugs inserted, before (PAR A) and after (PAR B), i.e., the specific and individual training described above. RESULTS/CONCLUSIONS: PARs B were always definitely higher than PARs A, both for all tested frequencies and the corresponding average values, which were automatically detected by E-A-RfitTM. Furthermore the same PARs B were decidedly lower than the respective SNRs supplied by the manufacturer on the basis of laboratory assessments. These data prove that specific and individual training for workers improves the performance of earplugs, contributing to a more appropriate secondary prevention of the effects of noise on hearing; they also prove that the real attenuation recorded in workers are always lower than those supplied by the manufacturer of the devices. It is recommended that the E-A-RfitTM system, which allowed these results to be achieved objectively, should be normally used to assess exposure to noise in workers, when HPDs are worn. PMID- 26154472 TI - Dermal exposure and risk assessment of tebuconazole applicators in vineyards. AB - INTRODUCTION: Models used in the pre-marketing evaluation do not cover all work scenarios and may over- or underestimate exposure. OBJECTIVES: Uncertainties present in the extrapolation from pre-marketing to the post-marketing warrant exposure and risk assessment in real-life working conditions. METHODS: Seven vineyard pesticide applicators were followed for a total of 12 work-days. A data collection sheet was developed specifically for this study. Workers' body exposure, hands, and head exposure were measured. Tebuconazole was analyzed using LC-MS/MS. RESULTS: Median potential and actual body exposures were 22.41 mg/kg and 0.49 mg/kg of active substance applied, respectively. The median protection factor provided by the coverall was 98% (range: 90-99%). Hand exposure was responsible for 61% of total actual exposure, and was reduced by more than 50% in workers using gloves. The German Model underestimated the exposure in one work day, and grossly overestimated it in 3 work-days. CONCLUSIONS: High levels of potential body exposure were efficiently controlled by the cotton coverall. Use of personal protective devices, especially chemically-resistant gloves and head cover is the main determinant of skin protection. Field studies on pesticide exposure in real-life conditions and development of methods and tools for easier risk assessment are necessary to complement and confirm the risk assessment done in the authorization process. PMID- 26154473 TI - The Greek Pompeii in Health. AB - After the official request by Greece's prime minister for help, the country was put under the supervision of the Troika, that is, European Commission (EC), European Central Bank (ECB) and International Monetary Fund (IMF), and signed with them, in May 2010 the first and in February 2012 the second economic adjustment program, in exchange for financial packages, aiming at helping the country get out of its debt crisis, recover its lost growth and transform the national economy into a more sustainable model, including measures such as reductions in all public expenditures with efficient gains at the same time (1, 2). [...]. PMID- 26154475 TI - [Remembrance of Professor Emilio Sartorelli]. PMID- 26154477 TI - Graphene-Enveloped Poly(N-vinylcarbazole)/Sulfur Composites with Improved Performances for Lithium-Sulfur Batteries by A Simple Vibrating-Emulsification Method. AB - We prepared the Poly(N-vinylcarbazole)/sulfur@reduced graphene oxide (PVK/S@RGO) composites via a facile vibrating-emulsification synthesis method, which consist of the composites cores of large sulfur particles integrated into PVK conductive network and the conducting shell of reduced graphene oxide sheets. The PVK in the composites plays multiple roles in different processes. In preparation processes, PVK functions as dispersants to prevent sulfur particles from aggregating into excessively large size. And in the cycling test, PVK could play as additional electroactive binders and barriers to reinforce the electrode stability, accommodate volume change and reduce polysulfides shuttling. The resulting PVK/S@RGO composites containing 71 wt % sulfur exhibit excellent cycling performance and rate properties with a high discharge capacity of 843.5 mA h g( 1) and a charge capacity retention of 77% (only 0.07% capacity degradation per cycle) from 20th to 400th at 1 C, corresponding to an average Coulombic efficiency of over 94%. PMID- 26154478 TI - Cubozoan genome illuminates functional diversification of opsins and photoreceptor evolution. AB - Animals sense light primarily by an opsin-based photopigment present in a photoreceptor cell. Cnidaria are arguably the most basal phylum containing a well developed visual system. The evolutionary history of opsins in the animal kingdom has not yet been resolved. Here, we study the evolution of animal opsins by genome-wide analysis of the cubozoan jellyfish Tripedalia cystophora, a cnidarian possessing complex lens-containing eyes and minor photoreceptors. A large number of opsin genes with distinct tissue- and stage-specific expression were identified. Our phylogenetic analysis unequivocally classifies cubozoan opsins as a sister group to c-opsins and documents lineage-specific expansion of the opsin gene repertoire in the cubozoan genome. Functional analyses provided evidence for the use of the Gs-cAMP signaling pathway in a small set of cubozoan opsins, indicating the possibility that the majority of other cubozoan opsins signal via distinct pathways. Additionally, these tests uncovered subtle differences among individual opsins, suggesting possible fine-tuning for specific photoreceptor tasks. Based on phylogenetic, expression and biochemical analysis we propose that rapid lineage- and species-specific duplications of the intron-less opsin genes and their subsequent functional diversification promoted evolution of a large repertoire of both visual and extraocular photoreceptors in cubozoans. PMID- 26154479 TI - The impacts of marijuana dispensary density and neighborhood ecology on marijuana abuse and dependence. AB - BACKGROUND: As an increasing number of states liberalize cannabis use and develop laws and local policies, it is essential to better understand the impacts of neighborhood ecology and marijuana dispensary density on marijuana use, abuse, and dependence. We investigated associations between marijuana abuse/dependence hospitalizations and community demographic and environmental conditions from 2001 to 2012 in California, as well as cross-sectional associations between local and adjacent marijuana dispensary densities and marijuana hospitalizations. METHODS: We analyzed panel population data relating hospitalizations coded for marijuana abuse or dependence and assigned to residential ZIP codes in California from 2001 through 2012 (20,219 space-time units) to ZIP code demographic and ecological characteristics. Bayesian space-time misalignment models were used to account for spatial variations in geographic unit definitions over time, while also accounting for spatial autocorrelation using conditional autoregressive priors. We also analyzed cross-sectional associations between marijuana abuse/dependence and the density of dispensaries in local and spatially adjacent ZIP codes in 2012. RESULTS: An additional one dispensary per square mile in a ZIP code was cross-sectionally associated with a 6.8% increase in the number of marijuana hospitalizations (95% credible interval 1.033, 1.105) with a marijuana abuse/dependence code. Other local characteristics, such as the median household income and age and racial/ethnic distributions, were associated with marijuana hospitalizations in cross-sectional and panel analyses. CONCLUSIONS: Prevention and intervention programs for marijuana abuse and dependence may be particularly essential in areas of concentrated disadvantage. Policy makers may want to consider regulations that limit the density of dispensaries. PMID- 26154480 TI - Cessation of injecting drug use: The effects of health service utilisation, drug use and demographic factors. AB - BACKGROUND: Injecting drug use is associated with a range of harms, however cessation of injecting is rare. There is a lack of evidence on factors associated with cessation, notably those related to health services other than drug treatment. We examined the incidence and identified longitudinal correlates of first episode of cessation in a cohort of people who inject drugs (PWID). METHODS: Using discrete-time survival analysis, we examined correlates of the first episode of cessation (no self-reported injecting drug use in the past 12 months), including the use of health services, socio-demographics and drug related behaviour in a cohort of PWID recruited between 2008 and 2010. RESULTS: The cohort of 467 participants contributed 1527 person-years from recruitment to 2014. Under a fifth (17.8%) of people reported cessation of 12 months or more, yielding a cessation rate of 5.4 events per 100 person-years. Younger age (25-29 compared to 30 and above) (adjusted hazard ratio (AHR) 1.79, 95% confidence interval (CI) 1.07-3.00) and male gender (AHR 1.67, 95% CI 2.01-2.76) were positively associated with cessation, while past year use of benzodiazepines (AHR 0.45, 95% CI 0.28-0.72), arrest in the past year (AHR 0.50, 95% CI 0.30-0.83) and low SF-8 physical dimension score (AHR 0.42, 95% CI 0.20-1.88) were negatively associated with cessation. Outpatient service use had the largest effect on cessation (AHR 2.28, 95% CI 0.94-5.48, p=0.067). CONCLUSIONS: Low rates of cessation emphasise the need for sustained and comprehensive harm reduction services. The relationship between outpatient services and cessation suggests that further research into the use in health services among PWID is warranted. PMID- 26154481 TI - Percutaneous Cryoablation vs Partial Nephrectomy: Cost Comparison of T1a Tumors. AB - PURPOSE: To compare cost of percutaneous cryoablation vs open and robot-assisted partial nephrectomy of T1a renal masses from the hospital perspective. MATERIALS AND METHODS: We retrospectively compared cost, clinical and tumor data of 37 percutaneous cryoablations to 26 open and 102 robot-assisted partial nephrectomies. Total cost was the sum of direct and indirect cost of procedural and periprocedural variables. Clinical data included demographics, Charlson Comorbidity Index (CCI), hospitalization time, complication rate, ICU admission rate, and 30-day readmission rates. Tumor data included size, RENAL nephrometry score, and malignancy rate. Student's t-test was used for continuous variables and Fisher's exact or chi-square tests for categorical data. RESULTS: Mean total cost was lower for percutaneous cryoablation than open or robot-assisted partial nephrectomy: $6067 vs $11392 or $11830 (p<0.0001) with lower cost of procedure room: $1516 vs $3272 or $3254 (p<0.0001), room and board: $95 vs $1907 or $1106 (p<0.0001), anesthesia: $684 vs $1223 or $1468 (p<0.0001), and laboratory/pathology fees: $205 vs $804 or $720 (p<0.0001). Supply and device cost was higher than open: $2596 vs $1352 (p<0.0001), but lower than robot assisted partial nephrectomy: $3207 (p=0.002). Mean hospitalization times were lower for percutaneous cryoablation (p<0.0001), while age and CCI were higher (p<0.0001). No differences in tumor size, nephrometry score, malignancy rate complication, ICU, or 30-day readmission rates were observed. CONCLUSION: Percutaneous cryoablation can be performed at significantly lower cost than open and robotic partial nephrectomies for similar masses. PMID- 26154482 TI - Effect of soft tissue laxity of the knee joint on limb alignment correction in open-wedge high tibial osteotomy. AB - PURPOSE: Open-wedge high tibial osteotomy (HTO) cannot always accurately correct limb alignment, resulting in under- or over-correction. This study assessed the relationship between soft tissue laxity of the knee joint and alignment correction in open-wedge HTO. METHODS: This prospective study involved 85 patients (86 knees) undergoing open-wedge HTO for primary medial osteoarthritis. The mechanical axis (MA), weight-bearing line (WBL) ratio, and joint line convergence angle (JLCA) were measured on radiographs preoperatively and after 6 months, and the differences between the pre- and post-surgery values were calculated. Post-operative WBL ratios of 57-67 % were classified as acceptable correction. WBL ratios <57 and >67 % were classified as under- and over corrections, respectively. RESULTS: Preoperative JLCA correlated positively with differences in MA (r = 0.358, P = 0.001) and WBL ratio (P = 0.003). Difference in JLCA showed a stronger correlation than preoperative JLCA with differences in MA (P < 0.001) and WBL ratio (P < 0.001). Difference in JLCA was the only predictor of both difference in MA (P < 0.001) and difference in WBL ratio (P < 0.001). The difference between pre- and post-operative JLCA differed significantly between the under-correction, acceptable-correction, and over-correction groups (P = 0.033). Preoperative JLCA, however, did not differ significantly between the three groups. Neither preoperative JLCA nor difference in JLCA correlated with change in posterior slope. CONCLUSIONS: Preoperative degree of soft tissue laxity in the knee joint was related to the degree of alignment correction, but not to alignment correction error, in open-wedge HTO. Change in soft tissue laxity around the knee from before to after open-wedge HTO correlated with both correction amount and correction error. Therefore, a too large change in JLCA from before to after open-wedge osteotomy may be due to an overly large reduction in JLCA following osteotomy, suggesting alignment over-correction during surgery. LEVEL OF EVIDENCE: II. PMID- 26154483 TI - Comparative analysis of medial patellofemoral ligament length change pattern in patients with patellar dislocation using open-MRI. AB - PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction has become a common form of treatment for recurrent patellar dislocation. This study was performed using open-MRI to compare the length change pattern of MPFL in patients with a history of patellar dislocation to that in healthy subjects. METHODS: The subjects comprised 10 knees of 8 males and 13 knees of 12 females with a history of one or more patellar dislocations. The length of the MPFL was measured using open-MRI in both the leg-extended position and knee-flexed positions to analyse the length change pattern. RESULTS: The average MPFL lengths were 58.6 +/- 6.5 mm and 52.0 +/- 4.6 mm for males and females in the extended knee position, respectively. The length change pattern of the MPFL showed slight variation up to a flexion angle of 30 degrees and a clear decrease above 30 degrees . This pattern differed from that of normal MPFL. In terms of morphology, the fibre bundle of the damaged MPFL followed a convex course towards the side of the patellofemoral joint surface at a knee flexion angle of 60 degrees , whereas that of the normal MPFL followed a straight course. CONCLUSION: The in vivo damaged MPFL length change pattern was specific and differed distinctly from that of normal MPFL. The results of the present study suggested that MPFL fibres with a history of patellar dislocation lack sufficient tension at knee flexion angles of 0 degrees -60 degrees . However, further studies are needed to obtain a better understanding of cases with a patellar dislocation or postsurgical cases of MPFL reconstruction. LEVEL OF EVIDENCE: III. PMID- 26154485 TI - Unraveling the Role of Alkyl F on CH-pi Interactions and Uncovering the Tipping Point for Fluorophobicity. AB - Although fluorine often plays an influential role in molecular recognition, little is known about the effect of aliphatic fluorine on the CH-pi interaction in solution. A series of molecular balances were synthesized that contain fluorinated and nonfluorinated alkyl groups. Our findings indicate that fluorine's polarizing ability does enhance CH-pi binding and depends on molecular orientation. Surprisingly, when the terminal end of the alkyl group is completely fluorinated, the balance tips toward fluorophobicity and assumes an unusual constrained conformation. PMID- 26154484 TI - Real sequence effects on the search dynamics of transcription factors on DNA. AB - Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs. PMID- 26154487 TI - Estrogen, progesterone, and genistein differentially regulate levels of expression of alpha-, beta-, and gamma-epithelial sodium channel (ENaC) and alpha sodium potassium pump (Na+/K+-ATPase) in the uteri of sex steroid-deficient rats. AB - Estrogen, progesterone, and genistein could induce changes in uterine fluid volume and Na(+) concentration. Progesterone upregulates expression of epithelial sodium channel (ENaC) and Na(+)/K(+)-ATPase which contributed toward these changes. However, effects of estrogen and genistein were unknown. This study therefore investigated changes in expression of these proteins in the uterus under estrogen, progesterone, and genistein influences to further understand mechanisms underlying sex steroids and phytoestrogen effects on uterine fluid Na(+) regulation. In this study, uteri of ovariectomized female rats receiving 7 day treatment with genistein (25, 50, and 100 mg/kg/day), estrogen (0.8 * 10(-4) mg/kg/day), or progesterone (4 mg/kg/day) were harvested, and expression levels of alpha-, beta-, and gamma-ENaC proteins and messenger RNAs (mRNAs) and alpha Na(+)/K(+)-ATPase protein were determined by Western blotting (proteins) and real time polymerase chain reaction (mRNA). Meanwhile, distribution of alpha-, beta-, and gamma-ENaC and alpha-Na(+)/K(+)-ATPase proteins in the uterus was identified by immunohistochemistry. Our findings indicated that expression of alpha-, beta-, and gamma-ENaC proteins and mRNAs and alpha-Na(+)/K(+)-ATPase protein were enhanced under progesterone influence. Lower expressions were noted under estrogen and genistein influences compared to progesterone. Under estrogen, progesterone, and genistein influences, alpha- and beta-ENaC were distributed at apical membrane and gamma-ENaC was distributed at apical and basolateral membranes of uterine luminal epithelia. Under progesterone influence, alpha Na(+)/K(+)-ATPase was highly expressed at basolateral membrane. In conclusion, high expression of alpha-, beta-, and gamma-ENaC and alpha-Na(+)/K(+)-ATPase under progesterone influence would contribute toward increased uterine fluid Na(+) reabsorption, whereas lesser expression of these proteins under estrogen and genistein influences would contribute toward lower reabsorption of uterine fluid Na(+). PMID- 26154488 TI - Cafestol has a weaker inhibitory effect on osteoclastogenesis than kahweol and promotes osteoblast differentiation. AB - Bone homeostasis is regulated by a balance between osteoclast (OCL)-mediated bone resorption and osteoblast (OBL)-mediated bone formation. Thus, developing a compound that simultaneously inhibits OCL function and promotes OBL function would be useful as a new medical therapy for bone diseases. Here, we examined the effects of cafestol, a coffee diterpene, on the differentiation of OCLs and OBLs. Cafestol prevented OCL formation in a dose-dependent manner and suppressed the bone-resorbing activity of OCLs. Interestingly, the viability of OCLs treated with 10-50 uM cafestol was significantly higher than that of untreated cells. At the molecular level, cafestol markedly decreased RANKL-induced phosphorylation of extracellular signal-regulated kinase (Erk) and inhibitor of nuclear factor kappa B alpha (IkappaBalpha). Compared to kahweol, another coffee-specific diterpene, the inhibitory effects of cafestol were milder on OCL differentiation, and cafestol and kahweol showed different characteristics in induction of the phase IotaIota antioxidant enzymes and sensitivities in nuclear factor-erythroid 2 related factor 2 (Nrf2)-deficient BMMs. In addition to inhibiting OCLs, cafestol enhanced the differentiation of osteoblastic cells by increasing the mRNA levels of differentiation markers. Thus, cafestol inhibits OCL differentiation and promotes OBL differentiation, suggesting that cafestol may be a novel agent for bone diseases. PMID- 26154490 TI - Simulating Frequency-Domain Electron Paramagnetic Resonance: Bridging the Gap between Experiment and Magnetic Parameters for High-Spin Transition-Metal Ion Complexes. AB - We present a comparison of experimental and simulated frequency- and field-domain electron paramagnetic resonance (EPR) spectra of integer and half-integer high spin transition-metal ion complexes. For the simulation of EPR spectra a new tool within the EPR simulation software EasySpin is introduced, which allows for field and frequency-domain EPR simulations with the same theoretical model and the same set of spin Hamiltonian parameters. The utility of this approach is demonstrated on the integer-spin complexes NiBr2(PPh3)2 and [Tp2Mn]SbF6 (both S = 1) and the half-integer-spin Fe(III) porphyrins, hemin (Fe(PPIX)Cl) and Fe(TPP)Cl (both S = 5/2). We demonstrate that the combination of field- and frequency domain EPR techniques allows the determination of spin Hamiltonian parameters, in particular large zero-field splittings, with high accuracy. PMID- 26154489 TI - Low Testosterone Level and Risk of Alzheimer's Disease in the Elderly Men: a Systematic Review and Meta-Analysis. AB - Sex steroids can positively affect the brain function, and low levels of sex steroids may be associated with worse cognitive function in the elderly men. However, previous studies reported contrary findings on the relationship between testosterone level and risk of Alzheimer's disease in the elderly men. The objective of this study was to comprehensively assess the relationship between low testosterone level and Alzheimer's disease risk in the elderly men using a meta-analysis. Only prospective cohort studies assessing the influence of low testosterone level on Alzheimer's disease risk in elderly men were considered eligible. Relative risks (RRs) with 95% confidence intervals (95% CI) were pooled to assess the risk of Alzheimer's disease in elderly men with low testosterone level. Seven prospective cohort studies with a total of 5251 elderly men and 240 cases of Alzheimer's disease were included into the meta-analysis. There was moderate degree of heterogeneity among those included studies (I(2) = 47.2%). Meta-analysis using random effect model showed that low plasma testosterone level was significantly associated with an increased risk of Alzheimer's disease in elderly men (random RR = 1.48, 95% CI 1.12-1.96, P = 0.006). Sensitivity analysis by omitting one study by turns showed that there was no obvious change in the pooled risk estimates, and all pooled RRs were statistically significant. This meta-analysis supports that low plasma testosterone level is significantly associated with increased risk of Alzheimer's disease in the elderly men. Low testosterone level is a risk factor of worse cognitive function in the elderly men. PMID- 26154491 TI - The Importance of Being Prepared. PMID- 26154493 TI - Thermal and Chemical Stability of Thiol Bonding on Gold Nanostars. AB - The stability of thiol bonding on the surface of star-shaped gold nanoparticles was studied as a function of temperature in water and in a set of biologically relevant conditions. The stability was evaluated by monitoring the release of a model fluorescent dye, Bodipy-thiol (BDP-SH), from gold nanostars (GNSs) cocoated with poly(ethylene glycol) thiol (PEG-SH). The increase in the BDP-SH fluorescence emission, quenched when bound to the GNSs, was exploited to this purpose. A maximum 15% dye release in aqueous solution was found when the bulk temperature of gold nanostars solutions was increased to T = 42 degrees C, the maximum physiological temperature. This fraction reduces 3-5% for temperatures lower than 40 degrees C. Similar results were found when the temperature increase was obtained by laser excitation of the near-infrared (NIR) localized surface plasmon resonance of the GNSs, which are photothermally responsive. Besides the direct impact of temperature, an increased BDP-SH release was observed upon changing the chemical composition of the solvent from pure water to phosphate-buffered saline and culture media solutions. Moreover, also a significant fraction of PEG-SH was released from the GNS surface due to the increase in temperature. We monitored it with a different approach, that is, by using a coating of alpha-mercapto-omega-amino PEG labeled with tetramethylrhodamine isothiocyanate on the amino group, that after heating was separated from GNS by ultracentrifugation and the released PEG was determined by spectrofluorimetric techniques on the supernatant solution. These results suggest some specific limitations in the use of the gold-thiolate bond for coating of nanomaterials with organic compounds in biological environments. These limitations come from the duration and the intensity of the thermal treatment and from the medium composition and could also be exploited in biological media to modulate the in vivo release of drugs. PMID- 26154494 TI - Optimal random frequency range in transcranial pulsed current stimulation indexed by quantitative electroencephalography. AB - Given the recent results provided by previous investigations on transcranial pulsed current stimulation (tPCS) demonstrating its modulatory effects on cortical connectivity; we aimed to explore the application of different random pulsed frequencies. The utility of tPCS as a neuromodulatory technique for cognition performance will come as additional frequency ranges are tested with the purpose to find optimal operational parameters for tPCS. This study was designed to analyze the effects of tPCS using the following random frequencies; 1 5, 6-10, and 11-15 Hz compared with sham on quantitative electroencephalographic changes in the spectral power and interhemispheric coherence of each electroencephalographic frequency band. This was a parallel, randomized, double blinded, sham-controlled trial. Forty healthy individuals older than 18 years were eligible to participate. The main outcomes were differences in the spectral power analysis and interhemispheric coherence as measured by quantitative electroencephalography. Participants were randomly allocated to four groups of random frequency stimulation and received a single session of stimulation for 20 min with a current intensity of 2 mA delivered by bilateral periauricular electrode clips. We found that a random pulsed frequency between 6-10 Hz significantly increased the power and coherence in frontal and central areas for the alpha band compared with sham stimulation, while 11-15 Hz tPCS decreased the power for the alpha and theta bandwidth. Our findings corroborate the hypothesis that a random frequency ranging into the boundaries of 6-10 Hz induces changes in the naturally occurring alpha oscillatory activity, providing additional data for further studies with tPCS. PMID- 26154495 TI - Neuronal adhesion, proliferation and differentiation of embryonic stem cells on hybrid scaffolds made of xanthan and magnetite nanoparticles. AB - Hybrid scaffolds made of xanthan and magnetite nanoparticles (XCA/mag) were prepared by dipping xanthan membranes (XCA) into dispersions of magnetic nanoparticles for different periods of time. The resulting hybrid scaffolds presented magnetization values ranging from 0.25 emu g(-1) to 1.80 emu g(-1) at 70 kOe and corresponding iron contents ranging from 0.25% to 2.3%, respectively. They were applied as matrices for in vitro embryoid body adhesion and neuronal differentiation of embryonic stem cells; for comparison, neat XCA and commercial plastic plates were also used. Adhesion rates were more pronounced when cells were seeded on XCA/mag than on neat XCA or plastic dishes; however, proliferation levels were independent from those of the scaffold type. Embryonic stem cells showed similar differentiation rates on XCA/mag scaffolds with magnetization of 0.25 and 0.60 emu g(-1), but did not survive on scaffolds with 1.80 emu g(-1). Differentiation rates, expressed as the number of neurons obtained on the chosen scaffolds, were the largest on neat XCA, which has a high density of negative charge, and were smallest on the commercial plastic dishes. The local magnetic field inherent of magnetite particles present on the surface of XCA/mag facilitates synapse formation, because synaptophysin expression and electrical transmission were increased when compared to the other scaffolds used. We conclude that XCA/mag and XCA hydrogels are scaffolds with distinguishable performance for adhesion and differentiation of ESCs into neurons. PMID- 26154496 TI - Update on selenoprotein biosynthesis. AB - SIGNIFICANCE: Selenium is an essential trace element that is incorporated in the small but vital family of proteins, namely the selenoproteins, as the selenocysteine amino acid residue. In humans, 25 selenoprotein genes have been characterized. The most remarkable trait of selenoprotein biosynthesis is the cotranslational insertion of selenocysteine by the recoding of a UGA codon, normally decoded as a stop signal. RECENT ADVANCES: In eukaryotes, a set of dedicated cis- and trans-acting factors have been identified as well as a variety of regulatory mechanisms, factors, or elements that control the selenoprotein expression at the level of the UGA-selenocysteine recoding process, offering a fascinating playground in the field of translational control. It appeared that the central players are two RNA molecules: the selenocysteine insertion sequence (SECIS) element within selenoprotein mRNA and the selenocysteine-tRNA([Ser]Sec); and their interacting partners. CRITICAL ISSUES: After a couple of decades, despite many advances in the field and the discovery of many essential and regulatory components, the precise mechanism of UGA-selenocysteine recoding remains elusive and more complex than anticipated, with many layers of control. This review offers an update of selenoproteome biosynthesis and regulation in eukaryotes. FUTURE DIRECTIONS: The regulation of selenoproteins in response to a variety of pathophysiological conditions and cellular stressors, including selenium levels, oxidative stress, replicative senescence, or cancer, awaits further detailed investigation. Clearly, the efficiency of UGA-selenocysteine recoding is the limiting stage of selenoprotein synthesis. The sequence of events leading Sec-tRNA([Ser]Sec) delivery to ribosomal A site awaits further analysis, notably at the level of a three-dimensional structure. PMID- 26154498 TI - Hydrogenophaga luteola sp. nov. isolated from reed pond water. AB - A yellowish colored, Gram-staining negative, strictly aerobic, motile, rod-shaped bacterium, designated THG-SQE7(T), was isolated from reed pond water in Shangqiu, PR China. Comparative 16S rRNA gene sequence analysis indicated that strain THG SQE7(T) is most closely related to Hydrogenophaga pseudoflava ATCC 33668(T) (98.4 %), followed by Hydrogenophaga bisanensis K102(T) (97.6 %) and Hydrogenophaga flava CCUG 1658(T) (97.6 %). DNA-DNA hybridization showed 53.5, 36.0 and 22.5 % DNA re-association with H. pseudoflava KCTC 2348(T), H. bisanensis KCTC 12980(T) and H. flava KCTC 1648(T), respectively. Chemotaxonomic data revealed that strain THG-SQE7(T) possesses ubiquinone-8 as the only isoprenoid quinone, summed feature 3 (C16:1 omega7c and/or C16:1 omega6c), C16:0 and C18:1 omega7c as the major fatty acids. The major polar lipids were found to be phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C content was determined to be 63.7 mol%. These data corroborated the affiliation of strain THG SQE7(T) to the genus Hydrogenophaga. Thus, the isolate represents a novel species, for which the name Hydrogenophaga luteola sp. nov. is proposed, with THG SQE7(T) as the type strain (=KCTC 42501(T) = CCTCC AB 2014314(T) = JCM 30433(T)). PMID- 26154497 TI - In Silico/In Vivo Insights into the Functional and Evolutionary Pathway of Pseudomonas aeruginosa Oleate-Diol Synthase. Discovery of a New Bacterial Di-Heme Cytochrome C Peroxidase Subfamily. AB - As previously reported, P. aeruginosa genes PA2077 and PA2078 code for 10S-DOX (10S-Dioxygenase) and 7,10-DS (7,10-Diol Synthase) enzymes involved in long-chain fatty acid oxygenation through the recently described oleate-diol synthase pathway. Analysis of the amino acid sequence of both enzymes revealed the presence of two heme-binding motifs (CXXCH) on each protein. Phylogenetic analysis showed the relation of both proteins to bacterial di-heme cytochrome c peroxidases (Ccps), similar to Xanthomonas sp. 35Y rubber oxidase RoxA. Structural homology modelling of PA2077 and PA2078 was achieved using RoxA (pdb 4b2n) as a template. From the 3D model obtained, presence of significant amino acid variations in the predicted heme-environment was found. Moreover, the presence of palindromic repeats located in enzyme-coding regions, acting as protein evolution elements, is reported here for the first time in P. aeruginosa genome. These observations and the constructed phylogenetic tree of the two proteins, allow the proposal of an evolutionary pathway for P. aeruginosa oleate diol synthase operon. Taking together the in silico and in vivo results obtained we conclude that enzymes PA2077 and PA2078 are the first described members of a new subfamily of bacterial peroxidases, designated as Fatty acid-di-heme Cytochrome c peroxidases (FadCcp). PMID- 26154499 TI - Propane biostimulation in biologically activated carbon (BAC) selects for bacterial clades adept at degrading persistent water pollutants. AB - Biologically activated carbon (BAC) can be used in both municipal water and hazardous waste remediation applications to enhance contaminant attenuation in water; however, questions remain about how selective pressures can be applied to increase the capabilities of microbial communities to attenuate recalcitrant contaminants. Here we utilized flow-through laboratory columns seeded with municipally derived BAC and exposed to water from a local drinking water facility to query how propane biostimulation impacts resident microorganisms. Ecological analyses using high throughput phylogenetic sequencing revealed that while propane did not increase the total number of microbiological species, it did select for bacterial communities that were distinct from those without propane. Temporal extractions demonstrated that microbial succession was rapid and established in approximately 2 months. A higher density of propane monooxygenase genes and bacterial clades including the Pelosinus and Dechloromonas genera suggest an enhanced potential for the degradation of persistent water pollutants in propane-stimulated systems. However, the ecological selective pressure was exhausted in less than 15 cm of transit in this flow-through scenario (25 hour retention) indicating a pronounced zonation that could limit the size of a biostimulated zone and require physical mixing, hydraulic manipulation, or other strategies to increase the spatial impact of biostimulation in flow-through scenarios. PMID- 26154501 TI - Interplay of disorder and geometrical frustration in doped gadolinium gallium garnet. AB - The geometrically frustrated triangular antiferromagnet Gadolinium Gallium Garnet (Gd3Ga5O12 or GGG) exhibits a rich mix of short-range order and isolated quantum states. We investigate the effects of up to 1% neodymium substitution for gallium on the ac magnetic response at temperatures below 1 K in both the linear and nonlinear regimes. Substitutional disorder actually drives the system toward a more perfectly frustrated state, apparently compensating for the effects of imperfect gadolinium/gallium stoichiometry, while at the same time more closely demarcating the boundaries of isolated, coherent clusters composed of hundreds of spins. Optical measurements of the local Nd environment substantiate the picture of an increased frustration index with doping. PMID- 26154502 TI - Follow-up Surveillance After Endovascular Aneurysm Repair: Less Is More? PMID- 26154503 TI - Cascade rearrangement of furylcarbinols with hydroxylamines: practical access to densely functionalized cyclopentane derivatives. AB - This article describes the aza-Piancatelli rearrangement with hydroxylamines to 4 aminocyclopentenones and subsequent transformations that highlight the versatility of the cyclopentene scaffold and the value of the hydroxylamine nucleophile in this transformation. PMID- 26154504 TI - A Nationwide Study of Norwegian Patients with Hereditary Angioedema with C1 Inhibitor Deficiency Identified Six Novel Mutations in SERPING1. AB - Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by relapsing, non-pruritic swelling in skin and submucosal tissue. Symptoms can appear in early infancy when diagnosis is more difficult. In the absence of a correct diagnosis, treatment of abdominal attacks often lead to unnecessary surgery, and laryngeal edema can cause asphyxiation. A cohort study of 52 patients from 25 unrelated families in Norway was studied. Diagnosis of C1-INH HAE was based on international consensus criteria including low functional and/or antigenic C1-INH values and antigenic C4. As SERPING1 mutations in Norwegian patients with C1-INH-HAE are largely undescribed and could help in diagnosis, we aimed to find and describe these mutations. Mutation analysis of the SERPING1 gene was performed by Sanger sequencing of all protein coding exons and exon intron boundaries. Samples without detected mutation were further analyzed by multiplex ligation-dependent probe amplification to detect deletions and duplications. Novel mutations suspected to lead to splice defects were analyzed on the mRNA level. Fifty-two patients from 25 families were included. Forty-four (84,6%) suffered from C1-INH-HAE type I and eight (15,4%) suffered from C1-INH HAE type II. Pathogenic or likely pathogenic mutations were found in 22/25 families (88%). Thirteen unique mutations were detected, including six previously undescribed. There were three missense mutations including one mutation affecting the reactive center loop at codon 466, three nonsense mutations, three small deletions/duplications, three gross deletions, and one splice mutation. PMID- 26154505 TI - Glycoengineering of Chinese hamster ovary cells for enhanced erythropoietin N glycan branching and sialylation. AB - Sialic acid, a terminal residue on complex N-glycans, and branching or antennarity can play key roles in both the biological activity and circulatory lifetime of recombinant glycoproteins of therapeutic interest. In order to examine the impact of glycosyltransferase expression on the N-glycosylation of recombinant erythropoietin (rEPO), a human alpha2,6-sialyltransferase (ST6Gal1) was expressed in Chinese hamster ovary (CHO-K1) cells. Sialylation increased on both EPO and CHO cellular proteins as observed by SNA lectin analysis, and HPLC profiling revealed that the sialic acid content of total glycans on EPO increased by 26%. The increase in sialic acid content was further verified by detailed profiling of the N-glycan structures using mass spectra (MS) analysis. In order to enhance antennarity/branching, UDP-N-acetylglucosamine: alpha-1,3-D-mannoside beta1,4-N-acetylglucosaminyltransferase (GnTIV/Mgat4) and UDP-N acetylglucosamine:alpha-1,6-D-mannoside beta1,6-N-acetylglucosaminyltransferase (GnTV/Mgat5), was incorporated into CHO-K1 together with ST6Gal1. Tri- and tetraantennary N-glycans represented approximately 92% of the total N-glycans on the resulting EPO as measured using MS analysis. Furthermore, sialic acid content of rEPO from these engineered cells was increased ~45% higher with tetra sialylation accounting for ~10% of total sugar chains compared to ~3% for the wild-type parental CHO-K1. In this way, coordinated overexpression of these three glycosyltransferases for the first time in model CHO-K1 cell lines provides a mean for enhancing both N-glycan branching complexity and sialylation with opportunities to generate tailored complex N-glycan structures on therapeutic glycoproteins in the future. PMID- 26154506 TI - A Spatio-temporal Model of African Animal Trypanosomosis Risk. AB - BACKGROUND: African animal trypanosomosis (AAT) is a major constraint to sustainable development of cattle farming in sub-Saharan Africa. The habitat of the tsetse fly vector is increasingly fragmented owing to demographic pressure and shifts in climate, which leads to heterogeneous risk of cyclical transmission both in space and time. In Burkina Faso and Ghana, the most important vectors are riverine species, namely Glossina palpalis gambiensis and G. tachinoides, which are more resilient to human-induced changes than the savannah and forest species. Although many authors studied the distribution of AAT risk both in space and time, spatio-temporal models allowing predictions of it are lacking. METHODOLOGY/PRINCIPAL FINDINGS: We used datasets generated by various projects, including two baseline surveys conducted in Burkina Faso and Ghana within PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign) national initiatives. We computed the entomological inoculation rate (EIR) or tsetse challenge using a range of environmental data. The tsetse apparent density and their infection rate were separately estimated and subsequently combined to derive the EIR using a "one layer-one model" approach. The estimated EIR was then projected into suitable habitat. This risk index was finally validated against data on bovine trypanosomosis. It allowed a good prediction of the parasitological status (r2 = 67%), showed a positive correlation but less predictive power with serological status (r2 = 22%) aggregated at the village level but was not related to the illness status (r2 = 2%). CONCLUSIONS/SIGNIFICANCE: The presented spatio-temporal model provides a fine scale picture of the dynamics of AAT risk in sub-humid areas of West Africa. The estimated EIR was high in the proximity of rivers during the dry season and more widespread during the rainy season. The present analysis is a first step in a broader framework for an efficient risk management of climate-sensitive vector borne diseases. PMID- 26154507 TI - Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance. AB - The generation of induced pluripotent stem (iPS) cells holds great promise in regenerative medicine. The use of the transcription factors Oct4, Sox2, Klf4 and c-Myc for reprogramming is extensively documented, but comparatively little is known about soluble molecules promoting reprogramming. Here we identify the secreted cue Netrin-1 and its receptor DCC, described for their respective survival/death functions in normal and oncogenic contexts, as reprogramming modulators. In various somatic cells, we found that reprogramming is accompanied by a transient transcriptional repression of Netrin-1 mediated by an Mbd3/Mta1/Chd4-containing NuRD complex. Mechanistically, Netrin-1 imbalance induces apoptosis mediated by the receptor DCC in a p53-independent manner. Correction of the Netrin-1/DCC equilibrium constrains apoptosis and improves reprogramming efficiency. Our work also sheds light on Netrin-1's function in protecting embryonic stem cells from apoptosis mediated by its receptor UNC5b, and shows that the treatment with recombinant Netrin-1 improves the generation of mouse and human iPS cells. PMID- 26154508 TI - Novel mechanisms of platelet clearance and thrombopoietin regulation. AB - PURPOSE OF REVIEW: The human body produces and removes 10 platelets daily to maintain a normal steady-state platelet count. Platelet production must be tightly regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet removal and production in physiological and pathological conditions. This review will focus on different mechanisms of platelet clearance, with focus on the biological significance of platelet glycans. RECENT FINDINGS: The Ashwell-Morrell receptor (AMR) recognizes senescent, desialylated platelets under steady state conditions. Desialylated platelets and the AMR are the physiological ligand-receptor pair regulating hepatic thrombopoietin (TPO) mRNA production, resolving the longstanding mystery of steady state TPO regulation. The AMR-mediated removal of desialylated platelets regulates TPO synthesis in the liver by recruiting JAK2 and STAT3 to increase thrombopoiesis. SUMMARY: Inhibition of TPO production downstream of the hepatic AMR-JAK2 signaling cascade could additionally contribute to the thrombocytopenia associated with JAK1/2 treatment, which is clinically used in myeloproliferative neoplasms. PMID- 26154509 TI - The Influence of Seasonal Frugivory on Nutrient and Energy Intake in Wild Western Gorillas. AB - The daily energy requirements of animals are determined by a combination of physical and physiological factors, but food availability may challenge the capacity to meet nutritional needs. Western gorillas (Gorilla gorilla) are an interesting model for investigating this topic because they are folivore frugivores that adjust their diet and activities to seasonal variation in fruit availability. Observations of one habituated group of western gorillas in Bai Hokou, Central African Republic (December 2004-December 2005) were used to examine seasonal variation in diet quality and nutritional intake. We tested if during the high fruit season the food consumed by western gorillas was higher in quality (higher in energy, sugar, fat but lower in fibre and antifeedants) than during the low fruit season. Food consumed during the high fruit season was higher in digestible energy, but not any other macronutrients. Second, we investigated whether the gorillas increased their daily intake of carbohydrates, metabolizable energy (KCal/g OM), or other nutrients during the high fruit season. Intake of dry matter, fibers, fat, protein and the majority of minerals and phenols decreased with increased frugivory and there was some indication of seasonal variation in intake of energy (KCal/g OM), tannins, protein/fiber ratio, and iron. Intake of non-structural carbohydrates and sugars was not influenced by fruit availability. Gorillas are probably able to extract large quantities of energy via fermentation since they rely on proteinaceous leaves during the low fruit season. Macronutrients and micronutrients, but not digestible energy, may be limited for them during times of low fruit availability because they are hind gut fermenters. We discuss the advantages of seasonal frugivores having large dietary breath and flexibility, significant characteristics to consider in the conservation strategies of endangered species. PMID- 26154510 TI - Identification and functional analysis of a Masculinizer orthologue in Trilocha varians (Lepidoptera: Bombycidae). AB - We recently showed that the Masculinizer gene (Masc) plays a primary role in sex determination in the lepidopteran model insect Bombyx mori. However, it remains unknown whether this Masc protein-dependent sex determination system is conserved amongst lepidopteran insects or within the family Bombycidae. Here we cloned and characterized a Masc homologue (TvMasc) in Trilocha varians (Lepidoptera: Bombycidae), a species closely related to B. mori. To elucidate the role of TvMasc in the sex determination cascade of T. varians, TvMasc expression was knocked down in early embryos by the injection of small interfering RNAs (siRNAs) that targeted TvMasc mRNAs. Both female- and male-type splice variants of Tvdsx, a doublesex (dsx) homologue in T. varians were observed in control siRNA-injected embryos. By contrast, only female-type splice variants were observed in TvMasc siRNA-injected embryos. These results indicate that the TvMasc protein directly or indirectly regulates the splicing patterns of Tvdsx. Furthermore, we found that male-type splice variants of B. mori dsx (Bmdsx) were produced in TvMasc overexpressing BmN4 cells. The mRNA level of B. mori Imp, a gene whose product induces male-specific Bmdsx splicing also increased. These results suggest that Masc genes play similar roles in the sex-determination cascade in Bombycidae. PMID- 26154511 TI - Direct physician reporting is associated with reductions in radiation exposure in pediatric cardiac catheterizations. AB - OBJECTIVE: The objective is to quantify radiation dose in children undergoing cardiac catheterization and determine the impact of increased reporting transparency on total radiation exposure. BACKGROUND: Cardiac catheterization (cath) can result in significant radiation exposure in children. There has been growing interest in quantifying and reducing radiation exposure in pediatric cath procedures. Our center underwent a slight change in practice recently that resulted in direct physician reporting of radiation dose following every case. METHODS: We reviewed cath procedures across three different eras in four cath categories: post-heart transplant annual cath, unilateral pulmonary artery (PA) stent placement, pre-Fontan cath, and pre-Glenn cath. The eras were defined as: Era 1, 1/2009-1/2011; Era 2, 1/2011-9/2013; and Era 3, 9/2013-5/2014. In Era 3, the physician performing the cath was responsible for reporting the radiation data. RESULTS: Across the three eras, there were significant decreases in cumulative air KERMA (mGy) among all four cath categories. From Era 2 to Era 3, the greatest decreases in radiation were noted, particularly in dose area product (cGy.cm2) in the transplant annual evaluation and pre-Glenn cases. In Era 1, 2 cases (1.2%) had a frame rate reduction, while in Era 2, 22 cases (12.0%), and in Era 3, 83 cases (21.6%) had frame rate changes (P<0.01). CONCLUSIONS: Increased physician awareness of radiation exposure is associated with a significant reduction in radiation dose across a variety of cath procedures. This is seen not only by the overall reduction in radiation across case types, but also as the frame rate was more frequently changed during individual cases, indicating an important change in physician behavior and practice. PMID- 26154512 TI - Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice. AB - Ultraviolet B (UVB) irradiation may cause inflammation- and oxidative-stress dependent skin cancer and premature aging. Naringenin (1) has been reported to have anti-inflammatory and antioxidant properties, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress are still not known. Thus, the present study aimed to investigate the potential of naringenin to mitigate UVB irradiation-induced inflammation and oxidative damage in the skin of hairless mice. Skin edema, myeloperoxidase (neutrophil marker) and matrix metalloproteinase-9 (MMP-9) activity, and cytokine production were measured after UVB irradiation. Oxidative stress was evaluated by 2,2'-azinobis(3 ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability, ferric reducing antioxidant power (FRAP), reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, and gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR. The intraperitoneal treatment with naringenin reduced skin inflammation by inhibiting skin edema, neutrophil recruitment, MMP-9 activity, and pro-inflammatory (TNF-alpha, IFN gamma, IL-1beta, IL-4, IL-5, IL-6, IL-12, IL-13, IL-17, IL-22, and IL-23) and anti-inflammatory (TGF-beta and IL-10) cytokines. Naringenin also inhibited oxidative stress by reducing superoxide anion production and the mRNA expression of gp91phox. Therefore, naringenin inhibits UVB irradiation-induced skin damage and may be a promising therapeutic approach to control skin disease. PMID- 26154514 TI - Changing of the guards. PMID- 26154513 TI - 'My Virtual Dream': Collective Neurofeedback in an Immersive Art Environment. AB - While human brains are specialized for complex and variable real world tasks, most neuroscience studies reduce environmental complexity, which limits the range of behaviours that can be explored. Motivated to overcome this limitation, we conducted a large-scale experiment with electroencephalography (EEG) based brain computer interface (BCI) technology as part of an immersive multi-media science art installation. Data from 523 participants were collected in a single night. The exploratory experiment was designed as a collective computer game where players manipulated mental states of relaxation and concentration with neurofeedback targeting modulation of relative spectral power in alpha and beta frequency ranges. Besides validating robust time-of-night effects, gender differences and distinct spectral power patterns for the two mental states, our results also show differences in neurofeedback learning outcome. The unusually large sample size allowed us to detect unprecedented speed of learning changes in the power spectrum (~ 1 min). Moreover, we found that participants' baseline brain activity predicted subsequent neurofeedback beta training, indicating state dependent learning. Besides revealing these training effects, which are relevant for BCI applications, our results validate a novel platform engaging art and science and fostering the understanding of brains under natural conditions. PMID- 26154515 TI - The Effects of Load Carriage and Physical Fatigue on Cognitive Performance. AB - In the current study, ten participants walked for two hours while carrying no load or a 40 kg load. During the second hour, treadmill grade was manipulated between a constant downhill or changing between flat, uphill, and downhill grades. Throughout the prolonged walk, participants performed two cognitive tasks, an auditory go no/go task and a visual target detection task. The main findings were that the number of false alarms increased over time in the loaded condition relative to the unloaded condition on the go no/go auditory task. There were also shifts in response criterion towards responding yes and decreased sensitivity in responding in the loaded condition compared to the unloaded condition. In the visual target detection there were no reliable effects of load carriage in the overall analysis however, there were slower reaction times in the loaded compared to unloaded condition during the second hour. PMID- 26154517 TI - Burn Center Barrier Protocols During Dressing Change: A National Survey. AB - Infection control is a critical component of post-burn care with prevention of infection serving as a major cause of decreasing morbidity and mortality. One potential deterrent for infection is barrier protection during dressing changes; however, no evidence-based standard has been established among burn centers. The purpose of this study is to describe the current barrier techniques of American burn centers. A 24-question survey was sent to 121 burn center nurse managers within the United States. The survey was comprised of yes or no questions with comment sections available for further detail. Questions were constructed to gain insight into the variation and commonality that may exist between burn center barrier protocols. Forty-one out of 121 centers (34%) responded. Centers reported the use of head covers, masks, gowns, and gloves during admission of a new burn (71%, 82%, 95%, and 100% respectively); daily dressing changes (64%, 80%, 97%, and 100% respectively); postoperative dressing changes (64%, masks 80%, 97%, and 100% respectively); and dressing changes of a nonburn (66%, 82%, 97%, and 100% respectively). Burn centers reported their use of sterile gloves and gowns during typical burn dressing changes as occurring 20% and 10% of the time, respectively. Estimates for costs of these garments annually ranged from $0 to $250,000. A calculation performed for this study demonstrated that barrier garments used for dressing changes nationwide is approximately $2.43 million. We demonstrated the immense cost, to an institution and nationwide, of barrier garments used solely for dressing changes. PMID- 26154516 TI - Rural and Metropolitan Pediatric Burns in New South Wales and the Australian Capital Territory: Does Distance Make a Difference? AB - To determine if differences exist between children who sustain burns in rural areas and in metropolitan areas, an analysis of children presenting to the Burns Unit at The Children's Hospital at Westmead, from the January 1, 2008 to December 31, 2012 was performed. In all, 4326 children met the inclusion criteria, of which 21.2% came from rural regions. Just more than a quarter (26.0%) of rural children and 11.6% from metropolitan areas were Indigenous Australian (P < 0.0001). The average age of rural child was 4.5 years; metropolitan child was 3.9 years (P = 0.0001). Boys were more likely to sustain burns in both populations. Of the rural children, 40.8% sustained contact burns, 37.7% scald, and 12.5% flame. In contrast, 58.8% metropolitan children sustained scalds, 27.4% contact, and 4.5% flame. The home was the most common place for all burns to occur, but rural injuries commonly occurred outdoors. Burns were associated with risk-taking behavior in 15.3% rural and 8.7% metropolitan children (P < 0.0001). Nearly two thirds (65.9%) of children in both groups received adequate first aid (20 minutes of cool running water). Major burn injuries (>=10% Total BSA) occurred in 3.4% of rural and 2.1% metropolitan children (P = 0.02). Skin grafting was required in 28.3% rural and 16.3% metropolitan children (P = 0.0001). Nearly 32% of rural children required admission to the Burns Unit for >24 hours (15.9% metropolitan; P = 0.0001). Significant differences exist between burns sustained by rural and metropolitan children. This should be accounted for in burns prevention campaigns and the education of local health practitioners. PMID- 26154518 TI - An IrSi oxide film as a highly active water-oxidation catalyst in acidic media. AB - We report an acid-stable Si oxide-doped Ir oxide film (IrSi oxide film), made by metal organic chemical vapour deposition (MOCVD) of an Ir(V) complex for electrochemical water-oxidation. This is a successful improvement of catalytic ability and stability depending upon the pH of Ir oxide by doping of Si oxide. The turnover frequency (TOF) of the electrochemical water-oxidation by the IrSi oxide film is the highest of any Si oxide-doped Ir oxide materials and higher even than that of Ir oxide in acidic media. PMID- 26154519 TI - Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster. AB - The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe) and two temperate populations (the Netherlands and North Carolina) with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor. PMID- 26154520 TI - Protective effect on phenytoin-induced cognition deficit in pentylenetetrazol kindled mice: A repertoire of Glycyrrhiza glabra flavonoid antioxidants. AB - CONTEXT: Glycyrrhiza glabra L. (Febaceae) has been widely used in traditional medicine and scientifically explored for its anticonvulsant and memory improving potential. OBJECTIVE: The objective of this study is to investigate the effect of flavonoid rich fraction of G. glabra root extract against phenytoin-induced cognition deficit in pentylenetetrazol (PTZ) kindled mice. MATERIALS AND METHODS: The ethyl acetate fraction was initially screened in different in vitro free radical scavenging assays. For in vivo studies, the kindled mice in different groups were given 15 d post-treatment with phenytoin (25 mg/kg; p.o.) per se or in combination with varying doses of the fraction (5, 10, and 15 mg/kg; p.o.). Seizure severity score and cognitive functions were accessed using Racine's scale and passive shock avoidance paradigm, respectively on every 5th d after a PTZ challenge dose (35 mg/kg; i.p.). At the end of study, the animals were scarified for cerebral biochemistry. RESULTS: The fraction showed marked antioxidant activity indicated by low IC50 values in DPPH (20.9 ug/mL), nitric oxide radical scavenging (195.2 ug/mL), and capacity of hydrogen peroxide scavenging (3.4 ug/mL) assays. Treatment with phenytoin per se and along with the flavonoid rich fraction showed significant reduction in seizure severity score as compared to vehicle control. The combined-treated groups also showed improved cognitive functions indicated by reduced number of mistakes and increased step-down latency in passive shock avoidance paradigm. CONCLUSION: From the results, it can be concluded that the flavonoid rich fraction in combination with phenytoin reduces seizure severity and improve cognitive functions in PTZ-kindled mice. PMID- 26154521 TI - Evaluation of the cytotoxicity, cell-cycle arrest, and apoptotic induction by Euphorbia hirta in MCF-7 breast cancer cells. AB - CONTEXT: Euphorbia hirta L. (Euphorbiaceae) has been used as a folk remedy in Southeast Asia for the treatment of various ailments. OBJECTIVE: The current study evaluates the cytotoxicity, cell-cycle arrest, and apoptotic induction by E. hirta in MCF-7 breast cancer cells. MATERIALS AND METHODS: Cytotoxic activity of methanol extract of whole part of E. hirta was determined by the MTT assay at various concentrations ranging from 1.96 to 250.00 ug/mL in MCF-7 cells. Cell morphology was assessed by light and fluorescence microscopy. Apoptosis and cell cycle distribution were determined by annexin V staining and flow cytometry. DNA fragmentation, caspase activity, and reactive oxygen species (ROS) assays were performed using the commercially available kits. To identify the cytotoxic fraction, E. hirta extract was subjected to bioassay-guided fractionation. RESULTS: Euphorbia hirta exhibited significant inhibition of the survival of MCF 7 cells and the half inhibitory concentration (IC50) values was 25.26 ug/mL at 24 h. Microscopic studies showed that E. hirta-treated cells exhibited marked morphological features characteristic of apoptosis. Euphorbia hirta extract also had an ignorable influence on the LDH leakage and generating intracellular ROS. The flow cytometry study confirmed that E. hirta extract induced apoptosis in MCF 7 cells. Euphorbia hirta also resulted in DNA fragmentation in MCF-7 cells. Moreover, E. hirta treatment resulted in the accumulation of cells at the S and G2/M phases as well as apoptosis. The caspase activity study revealed that E. hirta extract induced apoptosis through the caspase-3-independent pathway by the activation of caspase-2, 6, 8, and 9. Euphorbia hirta hexane fraction, namely HFsub4 fraction, demonstrated highest activity among all the fractions tested with an IC50 value of 10.01 ug/mL at 24 h. DISCUSSION AND CONCLUSION: This study revealed that E. hirta induced apoptotic cell death and suggests that E. hirta could be used as an apoptosis-inducing anticancer agent for breast cancer treatment with further detailed studies. PMID- 26154522 TI - Analgesic activity of Gleditsia triacanthos methanolic fruit extract and its saponin-containing fraction. AB - CONTEXT: Gleditsia triacanthos L. (Leguminosae) pods are used in folk medicine for pain relief as anodyne and narcotic. OBJECTIVE: The objective of this study is to evaluate analgesic activity of Gleditsia triacanthos methanolic fruit extract (MEGT) and its saponin-containing fraction (SFGT). MATERIALS AND METHODS: Peripheral analgesic activity was assessed using the acetic acid-induced writhing model in mice at doses of 140, 280, and 560 mg/kg and formalin test in rats at 100, 200, and 400 mg/kg doses. Central analgesic activity was evaluated using the hotplate method in rats (100, 200, and 400 mg/kg). RESULTS: In the writhing test, six mice groups treated with MEGT and SFGT found ED50 values 268.2 and 161.2 mg/kg, respectively, displayed a significant decrease in writhing count compared with the group treated with standard drug indomethacin (14 mg/kg). SFGT (280 and 560 mg/kg) showed 64.94 and 70.78% protection, respectively, which are more than double % protection caused by indomethacin (31.82%). In the formalin test, MEGT and SFGT (ED50 values 287.6 and 283.4 mg/kg for phase I as well as 295.1 and 290.4 mg/kg for phase II, respectively) at 400 mg/kg showed significant % inhibition in both phase I (18.86 and 52.57%) and phase II (39.36 and 44.29%) with reference to 10 mg/kg indomethacin (56.0 and 32.29%). MEGT and SFGT caused significant delay in responses in hotplate model (ED50 values 155.4 and 200.6 mg/kg, respectively) compared with that of 10 mg/kg indomethacin at 30, 60, and 120 min. DISCUSSION AND CONCLUSION: Central and peripheral analgesic activities induced by Gleditsia triacanthos fruits might account for its uses in folk medicine. PMID- 26154523 TI - Fate of Radium in Marcellus Shale Flowback Water Impoundments and Assessment of Associated Health Risks. AB - Natural gas extraction from Marcellus Shale generates large quantities of flowback water that contain high levels of salinity, heavy metals, and naturally occurring radioactive material (NORM). This water is typically stored in centralized storage impoundments or tanks prior to reuse, treatment or disposal. The fate of Ra-226, which is the dominant NORM component in flowback water, in three centralized storage impoundments in southwestern Pennsylvania was investigated during a 2.5-year period. Field sampling revealed that Ra-226 concentration in these storage facilities depends on the management strategy but is generally increasing during the reuse of flowback water for hydraulic fracturing. In addition, Ra-226 is enriched in the bottom solids (e.g., impoundment sludge), where it increased from less than 10 pCi/g for fresh sludge to several hundred pCi/g for aged sludge. A combination of sequential extraction procedure (SEP) and chemical composition analysis of impoundment sludge revealed that Barite is the main carrier of Ra-226 in the sludge. Toxicity characteristic leaching procedure (TCLP) (EPA Method 1311) was used to assess the leaching behavior of Ra-226 in the impoundment sludge and its implications for waste management strategies for this low-level radioactive solid waste. Radiation exposure for on-site workers calculated using the RESRAD model showed that the radiation dose equivalent for the baseline conditions was well below the NRC limit for the general public. PMID- 26154524 TI - Second to fourth digit ratio, sex differences and antropometric measuments: their relationship in children. AB - BACKGROUND: The aim of this study was to determine the effect of socio demographic factors and anthropometric measurements on 2/4 digit ratio in the school aged children. METHODS: This cross-sectional study was completed in primary and secondary schools in the city center of Canakkale, Turkey. The students were seated at a table by the responsible doctor, and were asked to extend the palm of the right and left hand in the schools. Using a Vernier Caliper the 2/4 fingers were measured from the palm twice, and the results were noted together with socio-demographic information. Weight, length, waist and hip measurements were taken while students were behind a folding screen. RESULTS: A total of 1860 students from 5-14 years were included in the study. The right hand 2/4 digit ratio was 0.9765+/-0.035 and the left hand ratio was 0.9716+/-0.036 for girls. For the boys the ratios were 0.9688+/-0.035 for right hand and 0.9653+/ 0.033 for left hand. The digit ratios of girls were significantly higher than boys and the right hand ratio was even greater. The 2/4 digit measurements of both hands of students were positively correlated with each other. In regression model left hand 2/4 ratio is dependent hip circumference, monthly income and gender as adjusted r2 0.051. The right hand 2/4 ratio was dependent gender, monthly income, hip circumference and birthweight as adjusted r2 0.041. CONCLUSIONS: The 2/4 digit ratio of school-aged in Turkish children differed based on gender. Digit ratios depend on the hip circumference, gender (girls have higher ratio), birthweight, gestation week and monthly income. Further research, especially the effect of monthly income, is needed. PMID- 26154525 TI - Children's drawings as a window into creativity: ratings of disrupted emotionality in children's drawings predict creativity in narrative play construction. PMID- 26154526 TI - Association of oral breathing with dental malocclusions and general health in children. AB - BACKGROUND: The aims of this study were to analyze the association of oral breathing with dental malocclusions and aspects of general health such as acute illnesses, oxygen saturation in blood and its possible implication in the process of nutrition. METHODS: A prevalence analytic study was carried out. Five dentists explored to children between 6 and 12 years and measured their oxygen saturation. Parents completed a questionnaire of 11 items about general health (colds, ear infections, tonsillitis and taking antibiotics) and the food preferences of their children. At the end, children were classified in oral breathing group (prevalence cases) or nasal breathing group (controls). RESULTS: There were statistical differences between cases (452 children) and controls (752 children) in the facial morphometric measurements. Oral breathing children had statistically less percentage of oxygen saturation than controls (92.3+/-3.3% versus 96.5+/-2.3%), took less time to have lunch and preferred less consistent and sugary food. Cases had had more prevalence of pathologies in the last year and of taking the antibiotics. This group also had higher prevalence of allergies compared with controls group (P<0.001). CONCLUSIONS: Oral breathing is significantly associated with specific dental malocclusions and important aspects of general health such as oxygen saturation and the nutrition. On the same line, oral breathing is related to a significantly higher prevalence of allergies and a significantly more likely getting sick and taking medication. PMID- 26154527 TI - Canines mesiodistal measures as the key to sex prediction: a systematic review and meta-analysis. AB - INTRODUCTION: The purpose of this study was to systematically review the literature about canine measures to determine whether their variations had any role in sex determination. EVIDENCE ACQUISITION: The study searched MEDLINE database from 2004-2014 according PRISMA guidelines. Search terms included "canine teeth," "dental crowns," "dentition," "permanent," "sex dimorphism," "forensic anthropology," "review literature." EVIDENCE SYNTHESIS: Four hundred forty-three studies were identified in the search strategy and 11 were included. Eight analysed mean differences of maxillary right canines' mesiodistal (MD) measures between male and female. There was no significant mean difference in two studies of eight (standardised mean difference [SMD]=0.150 and 0.268, respectively). According to all eight studies that reviewed them, maxillary right canines MD measures mean difference was significantly different (SMD=0.479). All five studies, which described maxillary left canines MD measures, found the mean, were significantly different (SMD=0.424). Ten studies found the same result for mandibular right canines (SMD=0.696). Eight studies found mandibular left canines MD measures and mean significantly different (SMD=0.685). CONCLUSIONS: The most significant SMD was between male and female mandibular canines (right and left), mesiodistal width 0.696 and 0.685 respectively. Consequently, these canines are the most important to the sex prediction. PMID- 26154528 TI - A comparative study of surgical outcomes using a Colorado microdissection needle versus standard-size needle electrocautery in one-stage hypospadias repair using a transverse preputial island flap. AB - BACKGROUND: The purpose of this study was to compare the surgical outcomes of a Colorado microdissection needle (CMN) with that of a standard-size electrocautery needle in one-stage hypospadias repair using a transverse preputial island flap (TPIF). METHODS: The records of patients who received hypospadias repair from September 2012 to October 2013 were retrospectively reviewed. Patients were divided into a group that received repair using a CMN and those in which a standard-size electrocautery needle was used. Data collected and compared included age, types of hypospadias, duration of surgery, intraoperative blood loss, and postoperative edema and complications. RESULTS: There were 51 patients in the CMN group and 44 in the standard needle group, and the groups were similar with respect to age and type of hypospadias. The median surgery time for the CMN group was significantly shorter than that of the standard group (15.7 minutes vs. 20.6 minutes, respectively, P<0.001). At postoperative day 7 and day 30, the CMN group had significantly less patients with edema than the standard needle group (31.4% vs. 65.9%, P<0.01; and 37.3% vs. 79.5%, P<0.001, respectively). The overall complication rate has no significant difference between two groups. CONCLUSIONS: The use of CMN for tissue dissection and separation in hypospadias repair can facilitate foreskin degloving, shape the flap in a more efficient way, and help maintain adequate blood supply for the new urethra and its skin coverage. PMID- 26154529 TI - Use of an Intravascular Heat Exchange Catheter and Intravenous Lipid Emulsion for Hypothermic Cardiac Arrest After Cyclobenzaprine Overdose. AB - In this case report, a 22-year-old male developed severe hypothermia after an accidental overdose of cyclobenzaprine. During transport, the patient developed cardiac arrest. He received active rewarming measures, including pleural lavage, gastric lavage, an intravascular heat exchange catheter, and cardiopulmonary bypass. Intravenous lipid emulsion (ILE) was also administered. A discussion of cyclobenzaprine toxicity, hypothermia, ILE, and accidental hypothermic cardiac arrest follows. PMID- 26154530 TI - Aging voice and the laryngeal muscle atrophy. AB - OBJECTIVES/HYPOTHESIS: To study by means of morphometric measurements the severity of vocal muscle atrophy in the elderly. STUDY DESIGN: Cadaver study. SETTING: Universidade Estadual Paulista (UNESP), Botucatu Medical School, Brazil. SUBJECTS AND METHODS: Thirty vocal folds were collected from necropsies distributed into three groups: aged 60 to 75 years (n=10); aged 76 to 90 years (n=10); and a control group aged 30 to 50 years (n=10). Specimens for histology were obtained from the middle portion of the vocal folds. The stained specimens were analyzed using Axion Vision software (coupled to a Zeiss [Oberkochen, Germany] microscope) and used in the morphometric analyses conducted with the ImageJ software. The diameters of 200 muscle fibers from each slide were measured, and the mean values were statistically analyzed. RESULTS: The mean values of the diameters of the vocal muscle fibers of the elderly age groups were smaller than in the control: control (30-50 years: 16.389 MUm); elderly (60-75 years: 14.412 MUm; 76-90 years: 14.162 MUm) (P<0.01). No statistical differences were observed between genders. CONCLUSION: The morphometric analysis showed smaller diameters of vocal muscle fibers in the elderly when compared to controls, demonstrating the atrophy of the muscle. No statistical differences were observed between genders. LEVEL OF EVIDENCE: N/A. PMID- 26154531 TI - Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma. AB - The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States. PMID- 26154532 TI - Direct Liquid Sampling for Corona Discharge Ion Mobility Spectrometry. AB - We present a new technique suitable for direct liquid sampling and analysis by ion mobility spectrometry (IMS). The technique is based on introduction of a droplet stream to the IMS reaction region. The technique was successfully used to detect explosives dissolved in methanol and oil as well as to analyze amino acids and dipeptides. One of the main advantages of this technique is its ability to analyze liquid samples without the requirement of any special solution. PMID- 26154533 TI - Possible Association of IFN-gamma Gene -316A/G SNP with Humoral Immune Response to Killed H5N1 HPAI Vaccine in a Red Junglefowl Population. AB - To understand the role of interferon (IFN)-gamma gene (IFNG) single-nucleotide polymorphisms (SNPs) in the resistance to H5N1 highly pathogenic avian influenza (HPAI), we determined the SNPs, the log2-transformed specific antibody titers, and ex vivo recall antigen-specific IFN-gamma production by peripheral blood mononuclear cells (PBMCs) in 62 red junglefowls (Gallus gallus) immunized twice with inactivated H5N1 HPAI vaccine. Consequently, 52 SNPs were detected in the amplified 1137-bp length covering the promoter region and all exons, with +2133A/T SNP in the coding DNA sequence that caused a missense mutation and was identified in G. gallus for the first time. For -316A/G SNP genotypes, the chi squared test showed that the bird sample was in the Hardy-Weinberg equilibrium (P=0.369>0.05), and the least squares analysis revealed an increasing tendency in the antibody titers with G to A substitution so that a significant difference occurred between the AA genotype (8.031+/-0.247) and the GG genotype (6.571+/ 0.528) (P=0.015<0.05, 95% confidence interval [CI]: 0.0004-0.0866), as basically consistent with the antigen-induced IFN-gamma protein expression, which indicated possible association of the -316A/G SNP with a secondary humoral immune response to the HPAI vaccine in the bird population. These findings may help to improve genetic resistance using cross-breeding and enhance HPAI vaccine-induced immunity in chicken production. PMID- 26154535 TI - Association of ACE and MDR1 Gene Polymorphisms with Steroid Resistance in Children with Idiopathic Nephrotic Syndrome. AB - AIM: The purpose of the study was to investigate the distribution of insertion/deletion (I/D) polymorphisms of the angiotensin-converting enzyme (ACE) gene and three exonic polymorphisms of the multidrug resistance 1 (MDR1) gene (C3435T, C1236T, and G2677T) in children diagnosed with idiopathic nephrotic syndrome (INS). MATERIALS AND METHODS: The study group consisted of 100 healthy controls and 150 INS patients, of which 50 were steroid resistant. Genomic DNA from blood samples was isolated from both of these groups and genotyping of the ACE and MDR1 genes was performed by polymerase chain reaction (PCR) using specific primers. RESULTS: There was no significant difference observed in the genotypic distribution and D allele frequency of the ACE gene. The two single nucleotide polymorphisms (SNPs), C1236T and C3435T, of the MDR1 gene showed no significance, whereas the SNP G2677T/A was significantly associated with the genotypes GT and GA of the MDR1 gene, indicating it may be a potential marker to detect drug resistance. CONCLUSION: Screening these polymorphisms will pave the way to better understand the molecular mechanisms of the disease, which may be useful in developing targeted therapies for INS patients. PMID- 26154536 TI - Rapid improvement of hereditary neuropathy with liability to pressure palsies following cubital tunnel release. PMID- 26154537 TI - Clinical aspects of influenza A(H1N1)pdm09 cases reported during the pandemic in Brazil, 2009-2010. AB - OBJECTIVE: To describe the clinical aspects of cases of influenza A(H1N1)pdm09 in Brazil. METHODS: A descriptive study of cases reported in Sistema de Informacao de Agravos de Notificacao (SINAN), 2009-2010. RESULTS: As the final classification, we obtained 53,797 (56.79%) reported cases confirmed as a new influenza virus subtype, and 40,926 (43.21%) cases discarded. Fever was the most common sign, recorded in 99.74% of the confirmed and 98.92% of the discarded cases. Among the confirmed cases, the presence of comorbidities was reported in 32.53%, and in 38.29% of the discarded cases. The case fatality rate was 4.04%; 3,267 pregnant women were confirmed positive for influenza A new viral subtype and 2,730 of them were cured. The case fatality rate of pregnant women was 6.88%. CONCLUSION: The findings suggested concern of the health system with pregnant women, and patients with comorbidities and quality of care may have favored a lower mortality. We recommend that, when caring for patients with severe respiratory symptoms, with comorbidities, or pregnant women, health professionals should consider the need for hospital care, as these factors make up a worse prognosis of infection by the pandemic influenza virus. PMID- 26154538 TI - One-year follow-up of neurological status of patients after cardiac arrest seen at the emergency room of a teaching hospital. AB - OBJECTIVE: To describe neurological status and associated factors of survivors after cardiac arrest, upon discharge, and at 6 and 12 month follow-up. METHODS: A cohort, prospective, descriptive study conducted in an emergency room. Patients who suffered cardiac arrest and survived were included. A one-year consecutive sample, comprising 285 patients and survivors (n=16) followed up for one year after discharge. Neurological status was assessed by the Cerebral Performance Category before the cardiac arrest, upon discharge, and at 6 and 12 months after discharge. The following factors were investigated: comorbidities, presence of consciousness upon admission, previous cardiac arrest, witnessed cardiac arrest, location, cause and initial rhythm of cardiac arrest, number of cardiac arrests, interval between collapse and start of cardiopulmonary resuscitation, and between collapse and end of cardiopulmonary resuscitation, and duration of cardiopulmonary resuscitation. RESULTS: Of the patients treated, 4.5% (n=13) survived after 6 and 12 months follow-up. Upon discharge, 50% of patients remained with previous Cerebral Performance Category of the cardiac arrest and 50% had worsening of Cerebral Performance Category. After 6 months, 53.8% remained in the same Cerebral Performance Category and 46.2% improved as compared to discharge. After 12 months, all patients remained in the same Cerebral Performance Category of the previous 6 months. There was no statistically significant association between neurological outcome during follow-up and the variables assessed. CONCLUSION: There was neurological worsening at discharge but improvement or stabilization in the course of a year. There was no association between Cerebral Performance Category and the variables assessed. PMID- 26154539 TI - Characteristics of an outpatient chronic hepatitis B virus infection cohort. AB - OBJECTIVE: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. METHODS: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher's exact test, chi2, Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. RESULTS: 175 patients with mean age of 42.95+/-12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. CONCLUSION: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. PMID- 26154540 TI - Check-up and cardiovascular risk progression: is there a room for innovation? AB - OBJECTIVE: To evaluate the impact of traditional check-up appointment on the progression of the cardiovascular risk throughout time. METHODS: This retrospective cohort study included 11,126 medical records of asymptomatic executives who were evaluated between January, 2005 and October, 2008. Variables included participants' demographics characteristics, smoking habit, history of cardiovascular diseases, diabetes, dyslipidemia, total cholesterol, HDL, triglycerides, glucose, c-reactive protein, waist circumference, hepatic steatosis, Framingham score, metabolic syndrome, level of physical activity, stress, alcohol consumption, and body mass index. RESULTS: A total of 3,150 patients was included in the final analysis. A worsening was observed in all risk factors, excepting in smoking habit, incidence of myocardial infarction or stroke and in the number of individuals classified as medium or high risk for cardiovascular events. In addition, a decrease in stress level and alcohol consumption was also seen. CONCLUSION: The adoption of consistent health policies by companies is imperative in order to reduce the risk factors and the future costs associated with illness and absenteeism. PMID- 26154541 TI - Factors associated with functional impairment of elderly patients in the emergency departments. AB - OBJECTIVE: To assess the functional capacity of elderly patients in the emergency department as to Basic and Instrumental Activities of Daily Living. METHODS: A cross-sectional study of 200 elderly patients admitted to the emergency department of a teaching hospital in Sao Paulo (SP), Brazil. The functional capacity of the elderly was assessed by the Katz index and Lawton & Brody scale. Statistical analyses were performed using analysis of variance, Bonferroni correction, chi2 test, or the likelihood ratio test. RESULTS: Most seniors were independent (65%), and the degree of dependence was related to age, female gender, being single and widowed, and presence of cerebrovascular disease and dementia. The more dependent elderly for Instrumental Activities of Daily Living had increased dependence for Basic Activities. CONCLUSION: We emphasize the importance of assessing the functional capacity of the elderly in the emergency department as it provides data for the nursing care in order to minimize or to avoid their functional impairment. PMID- 26154542 TI - The impact of erlotinib use in non-small-cell lung cancer patients treated in a private reference general hospital and in a private cancer clinic from 2005 to 2011. AB - OBJECTIVE: To report the demographic data and clinical outcomes of non-small-cell lung cancer patients exposed to erlotinib in any line of treatment. METHODS: This was a retrospective cohort study of nonsmall-cell lung cancer patients from a reference general hospital and a private oncology clinic, who received erlotinib from 2005 to 2011. Statistical analysis was performed and we evaluated demographic data and response to treatment, by correlating the results of this first cohort published in Brazil with results of current literature. RESULTS: A total of 44 patients were included; 65.9% were diagnosed with adenocarcinoma, and 63.6% had metastatic disease. The mean age was 63.3 years. The median follow-up was 47.9 months. Epidermal growth factor receptor mutation screening was performed in 22.7% of patients (n=10), with mutation present in 30% of patients. The median overall survival was 46.3 months, and there was a higher probability of survival at 60 months for females compared to males (29.4% versus 15.8%; p=0.042). The other variables did not present significant statistical difference. CONCLUSION: We collected the largest cohort of patients with non-small-cell lung cancer who have used erlotinib in Brazil to date, and demonstrated that outcomes of patients treated at our clinic during the study period were consistent with the results of current literature in similar patients. PMID- 26154543 TI - Assessment of adherence to the guidelines for the management of nausea and vomiting induced by chemotherapy. AB - OBJECTIVE: To assess adherence of the prescribing physicians in a private cancer care center to the American Society of Clinical Oncology guideline for antiemetic prophylaxis, in the first cycle of antineoplastic chemotherapy. METHODS: A total of 139 chemotherapy regimens, of 105 patients, were evaluated retrospectively from 2011 to 2013. RESULTS: We observed 78% of non-adherence to the guideline rate. The main disagreements with the directive were the prescription of higher doses of dexamethasone and excessive use of 5-HT3 antagonist for low risk emetogenic chemotherapy regimens. On univariate analysis, hematological malignancies (p=0.005), the use of two or more chemotherapy (p=0.05) and high emetogenic risk regimes (p=0.012) were factors statistically associated with greater adherence to guidelines. Treatment based on paclitaxel was the only significant risk factor for non-adherence (p=0.02). By multivariate analysis, the chemotherapy of high emetogenic risk most correlated with adherence to guideline (p=0.05). CONCLUSION: We concluded that the adherence to guidelines is greater if the chemotherapy regime has high emetogenic risk. Educational efforts should focus more intensely on the management of chemotherapy regimens with low and moderate emetogenic potential. Perhaps the development of a computer generated reminder may improve the adherence to guidelines. PMID- 26154544 TI - Esophageal eosinophilia in pediatric patients with cerebral palsy. AB - OBJECTIVE: To describe the clinical picture, test results, and clinical evolution of patients with cerebral palsy associated with diagnosis of eosinophilic esophagitis, monitored at tertiary centre. METHODS: Cross-sectional, retrospective and descriptive study that evaluated the medical records data of pediatric patients with diagnosis of cerebral palsy and eosinophilic esophagitis in a tertiary center of pediatric gastroenterology between August 2005 and August 2013. RESULTS: Seven out of 131 patients with cerebral palsy had the diagnosis of eosinophilic esophagitis. The mean age at diagnosis of eosinophilic esophagitis was 52.3 months and the mean number of eosinophils in esophagus was 35 per high power field. Symptoms more frequent were recurrent vomiting and disphagia. Endoscopic alterations found were mucosal thickening, vertical lines, mucosal opacificacion and white plaques. CONCLUSION: The frequency of eosinophilic esophagitis found was higher than in general pediatric population. The investigation of eosinophilic esophagitis should be done regularly in those patients, once this entity could overlap other gastrointestinal diseases. PMID- 26154545 TI - Therapeutic play: preparing the child for the vaccine. AB - OBJECTIVE: To identify and compare behaviors of children during vaccination, who were prepared or not for the procedure using an instructional therapeutic play. METHODS: A quasi experimental study, with quantitative approach of 60 children aged 3 to 6 years. The child's reactions were recorded in a checklist. Data were analyzed using descriptive and inferential statistics and Fisher's test. RESULTS: The main reactions in the experimental group were stay still (25;83%) and spontaneously collaborate (24;80%). In the control group, the main reactions were cries and cling to parents (15; 50%), flushing (11;36.67%) and moving the body/agitated (10;33.3%). CONCLUSION: The reactions of cooperation were more frequent in the experimental group, while low acceptance was observed only in the control group. Therapeutic play has proved an important tool in preparing for the vaccine. PMID- 26154546 TI - Analysis of epidemiology, lifestyle, and psychosocial factors in patients with back pain admitted to an orthopedic emergency unit. AB - OBJECTIVE: To correlate epidemiological data, lifestyle, and psychosocial factors as predictors for clinical manifestation of back pain in patients treated at the orthopedic emergency unit of a Brazilian tertiary care hospital, and to evaluate their interest in participating in a hypothetical program for physical rehabilitation. METHODS: This is an observational cross-sectional study. We evaluated 210 patients from the emergency department of a tertiary hospital with a major complaint of back pain. We used: epidemiological multiple-choice questionnaires developed for this study; Oswestry questionnaire for physical disability; Hospital Anxiety and Depression Scale (HAD) scale. Data analyses were performed using SAS - Statistical Analysis System (SAS Institute, 2001). Measurements were performed with the SAS functions Proc MEANS and Proc Freq. RESULTS: The mean age was 39.1 years and there was no predominance between genders. The usual work activity was administrative (65.2% of cases). The mean body mass index was 26.0, indicating overweight. The majority (83.3%) of patients had low physical disability (Oswestry 0 - 40%). The number of medical visits in the previous 6 months (p=0.04) and the scores of anxiety and depression (p=0.05), independently, were correlated with physical disability. Most patients (77%) would agree to participate in a hypothetical program of physical rehabilitation for prevention of back pain. CONCLUSION: Patients with back pain complaints were predominantly young adults, sedentary or hypoactive, overweight, and with recurrent complaints of symptoms. Most participants had low levels of physical disability and would accept participation in a hypothetical physical rehabilitation program for the prevention of back pain. PMID- 26154547 TI - Benefits of maltodextrin intake 2 hours before cholecystectomy by laparotomy in respiratory function and functional capacity: a prospective randomized clinical trial. AB - OBJECTIVE: To evaluate the change in respiratory function and functional capacity according to the type of preoperative fasting. METHODS: Randomized prospective clinical trial, with 92 female patients undergoing cholecystectomy by laparotomy with conventional or 2 hours shortened fasting. The variables measured were the peak expiratory flow, forced expiratory volume in the first second, forced vital capacity, dominant handgrip strength, and non-dominant handgrip strength. Evaluations were performed 2 hours before induction of anesthesia and 24 hours after the operation. RESULTS: The two groups were similar in preoperative evaluations regarding demographic and clinical characteristics, as well as for all variables. However, postoperatively the group with shortened fasting had higher values than the group with conventional fasting for lung function tests peak expiratory flow (128.7+/-62.5 versus 115.7+/-59.9; p=0.040), forced expiratory volume in the first second (1.5+/-0.6 versus 1.2+/-0.5; p=0.040), forced vital capacity (2.3+/-1.1 versus 1.8+/-0.9; p=0.021), and for muscle function tests dominant handgrip strength (24.9+/-6.8 versus 18.4+/-7.7; p=0.001) and non-dominant handgrip strength (22.9+/-6.3 versus 17.0+/-7.8; p=0.0002). In the intragroup evaluation, there was a decrease in preoperative compared with postoperative values, except for dominant handgrip strength (25.2+/-6.7 versus 24.9+/-6.8; p=0.692), in the shortened fasting group. CONCLUSION: Abbreviation of preoperative fasting time with ingestion of maltodextrin solution is beneficial to pulmonary function and preserves dominant handgrip strength. PMID- 26154548 TI - Design of an instrument to measure the quality of care in Physical Therapy. AB - OBJECTIVE: To design an instrument composed of domains that would demonstrate physical therapy activities and generate a consistent index to represent the quality of care in physical therapy. METHODS: The methodology Lean Six Sigma was used to design the tool. The discussion involved seven different management groups staff. By means of brainstorming and Cause & Effect Matrix, we set up the process map. RESULTS: Five requirements composed the quality of care index in physical therapy, after application of the tool called Cause & Effect Matrix. The following requirements were assessed: physical therapist performance, care outcome indicator, adherence to physical therapy protocols, measure whether the prognosis and treatment outcome was achieved and Infrastructure. CONCLUSION: The proposed design allowed evaluating several items related to physical therapy service, enabling customization, reproducibility and benchmarking with other organizations. For management, this index provides the opportunity to identify areas for improvement and the strengths of the team and process of physical therapy care. PMID- 26154549 TI - Fetoscopy for meningomyelocele repair: past, present and future. AB - Meningomyelocele is a malformation with high prevalence, and one of its main comorbidities is Arnold-Chiari malformation type II. The intrauterine repair of this defect has been studied to reduce the progressive spinal cord damage during gestation. The purpose of the present review was to describe the evolution of fetal surgery for meningomyelocele repair. Searches on PubMed database were conducted including articles published in the last 10 years. Twenty-seven articles were selected, 16 experimental studies and 11 studies in humans. A recent study demonstrated that the fetal correction results in better prognosis of neurological and psychomotor development, but open surgery, which has being used widely, has considerable maternal risks. Studies in animal and human models show that the endoscopic approach is feasible and leads to lower maternal morbidity rates. Two endoscopic techniques are currently under assessment - one in Germany and another in Brazil, and we believe that the endoscopic approach will be the future technique for prenatal repair of this defect. PMID- 26154550 TI - Lung transplantation. AB - Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID- 26154551 TI - Pancreas transplantation: review. AB - Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone. PMID- 26154552 TI - Heart transplantation: review. AB - Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants. PMID- 26154553 TI - Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction. AB - Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor's cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID- 26154554 TI - Liver-specific magnetic resonance contrast medium in the evaluation of chronic liver disease. AB - The hepatobiliary-specific contrast medium (gadoxetic acid - Primovist(r)) is primarily used to improve detection and characterization of focal hepatic lesions, such as in chronic liver disease patients with suspected hepatocellular carcinoma. Since the contrast medium is selectively taken up by functioning hepatocytes in the late hepatobiliary phase, it helps to detect typical hepatocellular carcinoma, which show low signal intensity on this phase. This imaging feature also assists in differentiating regenerative/dysplastic nodules from early hepatocellular carcinomas (with over 90% accuracy), as well as hypervascular hepatocellular carcinomas from arterial pseudo-enhancement foci. Future perspectives include its use in quantification of hepatic function and fibrosis. PMID- 26154555 TI - Probabilistic graphic models applied to identification of diseases. AB - Decision-making is fundamental when making diagnosis or choosing treatment. The broad dissemination of computed systems and databases allows systematization of part of decisions through artificial intelligence. In this text, we present basic use of probabilistic graphic models as tools to analyze causality in health conditions. This method has been used to make diagnosis of Alzheimer's disease, sleep apnea and heart diseases. PMID- 26154556 TI - Fecal microbiota transplant by push enteroscopy to treat diarrhea caused by Clostridium difficile. AB - Clostridium difficile is the major etiological agent of pseudomembranous colitis and is found in up to 20% of adult inpatients. The recommended treatment is antibiotic therapy with metronidazole and/or vancomycin. However, the recurrence rate may reach up to 25% and it increases in each episode. The newest alternative to treat diarrhea due to recurrent Clostridium difficile is fecal microbiota transplantation. The procedure was performed in 12 patients, with a 6-month follow-up on 10 of them. Of the ten cases, bacterial recurrence was diagnosed in only one patient, after a course of antibiotic to treat urinary tract infection, without presenting with diarrhea. The particularity of our study, besides being an unprecedented event in South America, is the way to perform the infusion of fecal microbiota by enteroscopy. PMID- 26154557 TI - Letter to the editor: association between participation and compliance with Continuing Medical Education and care production by physicians: a cross-sectional study. Einstein (Sao Paulo). 2015;13(1):1-6. PMID- 26154558 TI - Urinary lithiasis: the perfect balance. PMID- 26154560 TI - Cochlear implantation: An assessment of quality and readability of web-based information aimed at patients. AB - OBJECTIVES: Patients should have access to high-quality health information websites on which to base their decision-making. There are concerns regarding the accuracy and quality of some health websites. We aimed to objectively measure website quality related to cochlear implantation. METHODS: Selected patient information websites were scored, depending on how highly they ranked on search engines and if they were ranked on more than one of the search engines used. The top 40 websites from three major search engines were analysed. The quality of each website was scored using the DISCERN tool and the readability was scored using the Flesch-Kincaid reading ease and the Gunning-Fog index. RESULTS: The average Flesch-Kincaid score was 49.7, giving an average reading age of a 15-17 years old, and the average Gunning-fog score was 13.1, which equals that of an 18 years old. CONCLUSION: Internet-based information regarding cochlear implantation is of varied quality and is written above the expected reading level of an average person. PMID- 26154561 TI - Malignant Transformation of Optic Nerve Melanocytoma into Melanoma Associated with Ocular Ischemic Syndrome and Oculocardiac Reflex: Case Report and Review of the Literature. AB - PURPOSE: To describe the clinical and pathological features of malignant transformation of an optic nerve melanocytoma over 25 years, associated with spontaneous extensive tumor necrosis, neovascular glaucoma, ocular ischemic syndrome, and oculocardiac reflex. PROCEDURES: A 60-year-old Caucasian female presented with acute severe left ocular pain and glaucoma with an intraocular pressure of 80 mmHg and bradycardia (28-40 beats/min). RESULTS: Histopathological examination of the enucleated eye showed features of malignant transformation of a spontaneously necrotic optic nerve melanocytoma associated with ocular ischemic syndrome and neovascular glaucoma. CONCLUSIONS: Yearly follow-up and awareness of possible but well-documented malignant transformation, even over several decades, is recommended. This case presents malignant transformation of an optic nerve melanocytoma associated with the common complications described in the literature over the years. Of particular interest was the development of oculocardiac reflex in this patient. PMID- 26154562 TI - Aqueous foams stabilized by chitin nanocrystals. AB - The aim of the present study was to explore the potential use of chitin nanocrystals, as colloidal rod-like particles, to stabilize aqueous foams. Chitin nanocrystals (ChN) were prepared by acid hydrolysis of crude chitin and foams were generated mainly by sonicating the respective dispersions. The foamability of the chitin nanocrystals was evaluated and the resulting foams were assessed for their stability, in terms of foam volume reduction and serum release patterns, during storage. Additionally, the samples were studied with light scattering and optical microscopy in order to explore the bubble size distribution and morphology of the foam. Nanocrystal concentration and charge density was varied to alter the packing of the crystals at the interface. At low concentrations of ChNs, foams were stable against coalescence and disproportionation for a period of three hours, whereas at higher concentrations, the foams were stable for several days. The enhanced stability of foams prepared with ChNs, compared to surfactant-stabilized foams, can be mainly attributed to the irreversible adsorption of the ChNs at the air-water interface, thereby providing Pickering stabilization. Both foam volume and stability of the foam were increased with an increase in ChNs concentration, and at pH values around the chitin's pKa (pH 7.0). Under these conditions, the ChNs show minimal electrostatic repulsion and therefore a higher packing of the nanocrystals is promoted. Moreover, decreased electrostatic repulsion enhances network formation between the ChNs in the aqueous films, thereby providing additional stability by gel formation. Overall, ChNs were proven to be effective in stabilizing foams, and may be useful in the design of Pickering-stabilized food grade foams. PMID- 26154559 TI - The genetic variant rs4073 A->T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration. AB - PURPOSE: To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking. METHODS: Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A->T, CFH rs1061170 T->C, ARMS2 rs10490924 G->T and C3 rs2230199 C->G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed. RESULTS: Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD. CONCLUSION: Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD. PMID- 26154563 TI - An EEG-fMRI Study on the Termination of Generalized Spike-And-Wave Discharges in Absence Epilepsy. AB - INTRODUCTION: Different studies have investigated by means of EEG-fMRI coregistration the brain networks related to generalized spike-and-wave discharges (GSWD) in patients with idiopathic generalized epilepsy (IGE). These studies revealed a widespread GSWD-related neural network that involves the thalamus and regions of the default mode network. In this study we investigated which brain regions are critically involved in the termination of absence seizures (AS) in a group of IGE patients. METHODS: Eighteen patients (6 male; mean age 25 years) with AS were included in the EEG-fMRI study. Functional data were acquired at 3T with continuous simultaneous video-EEG recording. Event related analysis was performed with SPM8 software, using the following regressors: (1) GSWD onset and duration; (2) GSWD offset. Data were analyzed at single-subject and at group level with a second level random effect analysis. RESULTS: A mean of 17 events for patient was recorded (mean duration of 4.2 sec). Group-level analysis related to GSWD onset respect to rest confirmed previous findings revealing thalamic activation and a precuneus/posterior cingulate deactivation. At GSWD termination we observed a decrease in BOLD signal over the bilateral dorsolateral frontal cortex respect to the baseline (and respect to GSWD onset). The contrast GSWD offset versus onset showed a BOLD signal increase over the precuneus-posterior cingulate region bilaterally. Parametric correlations between electro-clinical variables and BOLD signal at GSWD offset did not reveal significant effects. CONCLUSION: The role of the decreased neural activity of lateral prefrontal cortex at GSWD termination deserve future investigations to ascertain if it has a role in promoting the discharge offset, as well as in the determination of the cognitive deficits often present in patients with AS. The increased BOLD signal at precuneal/posterior cingulate cortex might reflect the recovery of neural activity in regions that are "suspended" during spike and waves activity, as previously hypothesized. PMID- 26154565 TI - Brannerite-Type Vanadium-Molybdenum Oxide LiVMoO6 as a Promising Anode Material for Lithium-Ion Batteries with High Capacity and Rate Capability. AB - Brannerite-type vanadium-molybdenum oxide LiVMoO6 is prepared by a facile liquid phase method, and its electrochemical properties as anode of lithium-ion batteries are comprehensively studied by means of galvanostatic charge-discharge profiles, rate performance, and cyclic voltammetry. In the working voltage between 3.0 and 0.01 V, LiVMoO6 delivers a high reversible capacity of more than 900 mAh g(-1) at the current density of 100 mA g(-1) and a superior rate capability with discharge capacity of ca. 584 and 285 mAh g(-1) under the high current densities of 2 and 5 A g(-1), respectively. Moreover, ex situ X-ray diffraction and X-ray photoelectron spectroscopy are utilized to examine the phase evolution and valence changes during the first lithiated process. A small amount of inserted Li(+) induces a decomposition of LiVMoO6 into Li2Mo2O7 and V2O5, which play the host during further lithiated processes. When being discharged to 0.01 V, most V(5+) change into V(3+)/V(2+), suggesting intercalation/deintercalation processes, whereas Mo(6+) are reduced into a metallic state on the basis of the conversion reaction. The insights obtained from this study will benefit the design of novel anode materials for lithium-ion batteries. PMID- 26154564 TI - Collectin liver 1 and collectin kidney 1 and other complement-associated pattern recognition molecules in systemic lupus erythematosus. AB - The objective of this study was to explore the involvement of collectin liver 1 (CL-L1) and collectin kidney 1 (CL-K1) and other pattern recognition molecules (PRMs) of the lectin pathway of the complement system in a cross-sectional cohort of systemic lupus erythematosus (SLE) patients. Concentrations in plasma of CL L1, CL-K1, mannan-binding lectin (MBL), M-ficolin, H-ficolin and L-ficolin were determined in 58 patients with SLE and 65 healthy controls using time-resolved immunoflourometric assays. The SLE patients' demographic, diagnostic, clinical and biochemical data and collection of plasma samples were performed prospectively during 4 months. CL-L1, CL-K1 and M-ficolin plasma concentrations were lower in SLE patients than healthy controls (P-values < 0.001, 0.033 and < 0.001, respectively). H-ficolin concentration was higher in SLE patients (P < 0.0001). CL-L1 and CL-K1 plasma concentrations in the individuals correlated in both patients and controls. Patients with low complement component 3 (C3) demonstrated a negative correlation between C3 and CL-L1 and CL-K1 (P = 0.022 and 0.031, respectively). Patients positive for anti-dsDNA antibodies had lower levels of MBL in plasma than patients negative for anti-dsDNA antibodies (P = 0.02). In a cross-sectional cohort of SLE patients, we found differences in the plasma concentrations of CL-L1, CL-K1, M-ficolin and H-ficolin compared to a group of healthy controls. Alterations in plasma concentrations of the PRMs of the lectin pathway in SLE patients and associations to key elements of the disease support the hypothesis that the lectin pathway plays a role in the pathogenesis of SLE. PMID- 26154568 TI - GERONTOLOGICAL NURSING IS YOUNG - NOT NEW. PMID- 26154566 TI - Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: a New Therapeutic Approach. AB - Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G protein Galphas that activates adenylate cyclase), the peptide substance P (SP) at high concentrations-is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert An antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK 1 receptor could be a new promising therapeutic target in PC. PMID- 26154567 TI - Rapid and Sensitive Isothermal Detection of Nucleic-acid Sequence by Multiple Cross Displacement Amplification. AB - We have devised a novel amplification strategy based on isothermal strand displacement polymerization reaction, which was termed multiple cross displacement amplification (MCDA). The approach employed a set of ten specially designed primers spanning ten distinct regions of target sequence and was preceded at a constant temperature (61-65 degrees C). At the assay temperature, the double-stranded DNAs were at dynamic reaction environment of primer-template hybrid, thus the high concentration of primers annealed to the template strands without a denaturing step to initiate the synthesis. For the subsequent isothermal amplification step, a series of primer binding and extension events yielded several single-stranded DNAs and single-stranded single stem-loop DNA structures. Then, these DNA products enabled the strand-displacement reaction to enter into the exponential amplification. Three mainstream methods, including colorimetric indicators, agarose gel electrophoresis and real-time turbidity, were selected for monitoring the MCDA reaction. Moreover, the practical application of the MCDA assay was successfully evaluated by detecting the target pathogen nucleic acid in pork samples, which offered advantages on quick results, modest equipment requirements, easiness in operation, and high specificity and sensitivity. Here we expounded the basic MCDA mechanism and also provided details on an alternative (Single-MCDA assay, S-MCDA) to MCDA technique. PMID- 26154569 TI - Cruciate Retaining Implant With Biomimetic Articular Surface to Reproduce Activity Dependent Kinematics of the Normal Knee. AB - Alterations in normal knee kinematics following total knee arthroplasty (TKA) arise in part from the non-anatomic articular geometry of contemporary implants. In this study, the kinematics of a novel posterior cruciate-retaining (CR) implant with anatomic (biomimetic) articular surface, were compared to that of contemporary CR implants during various simulated activities. Across different simulated activities the biomimetic-CR mimicked normal kinematic patterns more closely than contemporary CR implants. In particular, during deep knee bend and chair-sit, the biomimetic-CR showed medial pivot motion, while other CR implants showed abnormal motion including lateral pivot or no pivot, and paradoxical anterior sliding. Further in vivo and clinical studies are needed to determine whether such biomimetic implants can truly help to achieve a more normal feeling knee and improved patient satisfaction. PMID- 26154570 TI - Risk Factors of Heterotopic Ossification Following Total Hip Arthroplasty in Patients With Ankylosing Spondylitis. AB - This study was to identify the risk factors of heterotopic ossification (HO) after total hip arthroplasty (THA) in ankylosing spondylitis. We analyzed 47 hips (24 patients) with ankylosing spondylitis that underwent primary THA. The incidence of HO was 14.9%. The risk factors were divided into modifiable and nonmodifiable factors. Female gender (P=0.008), preoperative ankylosed hip (P<0.001), occurrence of HO in previous surgery (P=0.036) were nonmodifiable risk factors which increased the prevalence of HO. Of the various modifiable risk factors, elevated preoperative ESR (P=0.007), elevated preoperative CRP (P=0.004) and prolonged duration of surgery (P=0.014) were associated with increased occurrence of HO. Perioperative medical intervention to reduce inflammation (ESR and CRP) may help to decrease HO. PMID- 26154571 TI - The Impact of Magnetic Resonance Imaging on Prediction of Extraprostatic Extension and Prostatectomy Outcome in Patients with Low-, Intermediate- and High Risk Prostate Cancer: Try to Find a Standard. AB - PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (mpMRI) and to predict extracapsular extension (ECE), seminal vesicle (SV) infiltration, and a negative surgical margin (SM) status at radical prostatectomy (RP) for different prostate cancer (PC) risk groups. PATIENTS AND METHODS: In the study, 805 men underwent 3 tesla mpMRI without endorectal coil before MRI/transrectal ultrasonography-fusion guided prostate biopsy. MRIs were analyzed using the prostate imaging reporting and data system. The cohort was classified into risk groups according to National Comprehensive Cancer Network (NCCN) criteria. Of 132 men who subsequently underwent RP, pathologic stage and SM status at RP were used as reference. Retrospectively, we investigated a European Society of Urogenital Radiology (ESUR) score for ECE and SV-infiltration. Statistical analyses included regression analyses, receiver operating characteristics (ROC), and Youden Index to assess an ESUR-score cutoff. RESULTS: Area under the curve in ROC curve analyses was 0.82 for ESUR-ECE score to detect pT(3a)-disease and 0.77 for ESUR-SV score for pT(3b). Using a cutoff of 4 for ECE and of 2 for SV, the positive predictive value of the ECE-score for harboring pT(3) was 50.0%, 90.0%, and 88.8% for the low-, intermediate- and high-risk cohort. Retrospectively, the use of the ESUR-ECE score preoperatively would have changed the initial surgical plan, according to NCCN criteria, in 31.1% of patients. In the high-risk subgroup, 9/35 (25.7%) patients were correctly assessed as not harboring pT(3) by imaging (ECE score <4), and would have allowed secure robot-assisted radical prostatectomy and nerve-sparing surgery (NSS). When T3 suspicion on preoperative MRI would be taken into account, intraoperative frozen-sections (IFS) might avoid positive SM in 12/18 high-risk patients and an oncologic secure NSS in 8/20 intermediate-risk patients. CONCLUSION: Prediction of pT(3) disease is crucial to plan NSS and to achieve negative SM in RP. Standardized ECE scoring on mpMRI is an independent predictor of pT(3) and may help to plan RP with oncologic security, even in high-risk patients. In addition, it allows more accurate selection of a subgroup of patients for systematic and MRI-guided IFS. PMID- 26154572 TI - Obstructive Sleep Apnea Is an Independent Predictor of Postoperative Atrial Fibrillation in Cardiac Surgery. AB - OBJECTIVE: To test the hypothesis that obstructive sleep apnea (OSA) is a risk factor for development of postoperative atrial fibrillation (POAF) after cardiac surgery. DESIGN: Retrospective analysis. SETTING: Single-center university hospital. PARTICIPANTS: Five hundred forty-five patients in sinus rhythm preoperatively undergoing coronary artery bypass grafting (CABG), aortic valve replacement, mitral valve replacement/repair, or combined valve/CABG surgery from January 2008 to April 2011. INTERVENTIONS: Retrospective review of medical records. MEASUREMENTS AND MAIN RESULTS: Postoperative atrial fibrillation was defined as atrial fibrillation requiring therapeutic intervention. Of 545 cardiac surgical patients, 226 (41%) patients developed POAF. The risk was higher in 72 OSA patients than 473 patients without OSA (67% v 38%, adjusted hazard ratio 1.83 [95% CI: 1.30-2.58], p<0.001). Of the 32 OSA patients who used home positive airway pressure (PAP) therapy, 18 (56%) developed POAF compared with 29 of 38 (76%) patients who did not use PAP at home (unadjusted hazard ratio 0.63 [95% CI: 0.35-1.15], p = 0.13). CONCLUSION: OSA is significantly associated with POAF in cardiac surgery patients. Further investigation is needed to determine whether or not use of positive airway pressure in OSA patients reduces the risk of POAF. PMID- 26154573 TI - Airway and Ventilatory Management Options in Congenital Tracheoesophageal Fistula Repair. PMID- 26154574 TI - Intranodal Mapping Using Carbon Dye Results in More Accurate Lymph Node Staging in Colon Cancer Patients. AB - INTRODUCTION: Small nodal tumor infiltrates (SNTI)-defined as isolated tumor cells and micrometastases-are associated with worse disease-free and overall survival in stage I and II colon cancer patients. Their detection, however, remains challenging. The objective of the present study was to evaluate whether there is a correlation between the location of SNTI and phagocytosed carbon dye particles in sentinel lymph nodes (SLN) of colon cancer patients. MATERIALS AND METHODS: Isosulfan blue and carbon dye were injected intraoperatively near the tumor to mark the SLN. Serial sections of SLN were stained with hematoxylin-eosin and immunohistochemistry. Intranodal distribution of phagocytosed carbon particles was compared to the presence of SNTI. RESULTS: Of a cohort of 159 patients, 24 patients had SNTI in their lymph nodes (LN). SNTI were found in a total of 116 LN of which 66 were SLN and 50 were non-SLN. In 59, these 116 LN with SNTI phagocytosed carbon dye were found (50.9 %). Phagocytosed carbon dye was identified significantly more often in SLN (49 of 66 SNTI positive SLN) compared to 10 of 50 SNTI positive non-SLN (p < 0.001). In 52 out of 59 LN (88.1 %), phagocytosed carbon dye was in close proximity to SNTI. CONCLUSIONS: In the majority of patients, SNTI are located in the same SLN compartment as phagocytosed carbon dye particles. Our investigation provides evidence that the use of carbon dye facilitates SNTI detection and improves LN staging in colon cancer. Therefore, the concept of intranodal mapping-which has been previously described for melanoma-can be extended to colon cancer patients. PMID- 26154575 TI - Strategic Assessment of Trauma Care Capacity in Ghana. AB - BACKGROUND: This study aimed to assess availability of trauma care technology in Ghana. In addition, factors contributing to deficiencies were evaluated. By doing so, potential solutions to inefficient aspects of health systems management and maladapted technology for trauma care in low- and middle-income countries (LMICs) could be identified. METHODS: Thirty-two items were selected from the World Health Organization's Guidelines for Essential Trauma Care. Direct inspection and structured interviews with administrative, clinical, and biomedical engineering staff were used to assess the challenges and successes of item availability at 40 purposively sampled district, regional, and tertiary hospitals. RESULTS: Hospital assessments demonstrated marked deficiencies. Some of these were low cost, such as basic airway supplies, chest tubes, and cervical collars. Item non availability resulted from several contributing factors, namely equipment absence, lack of training, frequent stock-outs, and technology breakage. A number of root causes for these factors were identified, including ineffective healthcare financing by way of untimely national insurance reimbursements, procurement and stock-management practices, and critical gaps in local biomedical engineering and trauma care training. Nonetheless, local examples of successfully overcoming deficiencies were identified (e.g., public-private partnering, ensuring company engineers trained technicians on-the-job during technology installation or servicing). CONCLUSION: While availability of several low-cost items could be better supplied by improvements in stock-management and procurement policies, there is a critical need for redress of the national insurance reimbursement system and trauma care training of district hospital staff. Further, developing local service and technical support capabilities is more and more pressing as technology plays an increasingly important role in LMIC healthcare systems. PMID- 26154576 TI - Minimally Invasive Distal Pancreatectomy for Cancer: Short-Term Oncologic Outcomes in 1,733 Patients. AB - BACKGROUND: Data from high-volume institutions suggest that minimally invasive distal pancreatectomy (MIDP) provides favorable perioperative outcomes and adequate oncologic resection for pancreatic cancer; however, these outcomes may not be generalizable. This study examines patterns of use and short-term outcomes from MIDP (laparoscopic or robotic) versus open distal pancreatectomy (ODP) for pancreatic adenocarcinoma in the United States. METHODS: Adult patients undergoing distal pancreatectomy were identified from the National Cancer Database, 2010-2011. Multivariable modeling was applied to compare short-term outcomes from MIDP versus ODP for pancreatic adenocarcinoma. RESULTS: 1733 patients met inclusion criteria: 535 (31 %) had MIDP and 1198 (69 %) ODP. Use of MIDP increased 43 % between 2010 and 2011; the conversion rate from MIDP to ODP was 23 %. MIDP cases were performed at 215 hospitals, with 85 % of hospitals performing <10 cases overall. After adjustment, pancreatic adenocarcinoma patients undergoing MIDP versus ODP had a similar likelihood of complete resection (OR 1.48, p = 0.10), number of lymph nodes removed (RR 1.01, p = 0.91), and 30-day readmission rate (OR 1.02, p = 0.96); however, length of stay was shorter (RR 0.84, p < 0.01). CONCLUSIONS: Use of MIDP for cancer is increasing, with most centers performing a low volume of these procedures. Use of MIDP for body and tail pancreatic adenocarcinoma appears to have short-term outcomes that are similar to those of open procedures with the benefit of a shorter hospital stay. Larger studies with longer follow-up are needed. PMID- 26154577 TI - Comparison of Survival Outcomes Between Right Posterior Sectionectomy and Right Hepatectomy for Hepatocellular Carcinoma in Cirrhotic Liver: A Single-Centre Experience. AB - BACKGROUND: Right hepatectomy (RH) instead of right posterior sectionectomy (RPS) is commonly performed for hepatocellular carcinoma (HCC) in cirrhotic livers located lateral to the right hepatic vein in order to ensure adequate resection margin. This potentially increased the risk of postoperative liver failure. This study aims to compare survival outcomes and surgical morbidities between RH and RPS. METHODS: All patients between 2003 and 2013 with resection for solitary HCC in cirrhotic livers at segment 6/7 were reviewed. Baseline demographics, liver function, perioperative outcomes, and overall (OS) and disease-free survival (DFS) were compared between RH and RPS. RESULTS: Eighty-one patients were included in this study. Thirty-two patients had RH and forty-nine with RPS were selected as controls. Majority of the HCC patients (91.4 %) suffered from chronic hepatitis B. There was no significant difference in age, gender and Child-Pugh grade between the two groups. The median tumour size of RH group was 6 vs. 4 cm in the RPS group (p < 0.0001). Both groups had no statistical difference in resection margin and their associated morbidities. The 5-year OS for RH and RPS was 76 and 83.8 %, respectively (p = 0.766), whereas their corresponding DFS was 52.6 and 52.2 % (p = 0.859). Despite the discrepancy of tumour size among the two groups, there was no statistical difference in subgroup analysis based on their corresponding stage of disease. CONCLUSION: RPS can achieve similar OS and DFS as RH for HCC, and should be considered as the treatment of choice in order to optimise the postoperative remnant parenchymal liver functions. PMID- 26154578 TI - Immunohistochemical Expression of E-Cadherin in Atypical Parathyroid Adenoma. AB - BACKGROUND: Atypical parathyroid adenoma (APA) is a rare entity, sharing clinical symptoms like solid palpable mass in the neck, laboratory changes with very high serum calcium and parathyroid hormone levels, and some histopathological features with parathyroid carcinomas (PC). However, clinical behavior of APA seems to comply with benign parathyroid tumors (PA). There is some evidence that loss of the membranous staining pattern of E-Cadherin (E-Cad) suggests a key role of epithelial mesenchymal transition in the tumorigenesis of PC. Thus, the aim of this study was to compare clinical and surgical characteristics and immunohistochemical expression of E-Cad in APA, PC, and PA. METHODS: Data of patients who underwent surgery for primary hyperparathyroidism (pHPT) between 1985 and 2010 were retrospectively evaluated. All data were analyzed with special regard to distinctive criteria of APA, including trabecular growth, broad fibrous bands, nuclear atypia, mitosis, pseudocapsular invasion or strong adherence to the surrounding tissue, and potential invasive growth of a grossly altered and enlarged parathyroid gland. In addition, laboratory and clinical data were evaluated and additional immunohistochemical staining with E-Cad was performed in suspicious APA patients with available tissue. RESULTS: In 68 patients (39 female, 29 male), the parathyroid tumor was suspicious for APA. In 46 patients, a bilateral cervical exploration was performed. 15 patients underwent an en bloc resection including a hemithyroidectomy and lymphonodular dissection of the ipsilateral central compartment due to the malignant macroscopic aspect of the parathyroid. In seven patients, a focused parathyroid resection was done. The available parathyroid tissue of 38 APA patients was immunopositive for membranous E-Cad staining. During follow-up, only one patient with a successful initial surgery suffered from recurrent pHPT due to another solitary PA 10 years after initial surgery but without evidence of malignancy. CONCLUSIONS: In contrast to PC, parathyroid tumors suspicious for APA are characterized by a strong membranous E-Cad staining and, like PA, by a benign clinical course. PMID- 26154579 TI - Enantiospecific Synthesis of Both Enantiomers of the Longtailed Mealybug Pheromone and Their Evaluation in a New Zealand Vineyard. AB - The irregular monoterpenoid sex pheromone of Pseudococcus longispinus and its enantiomer were prepared from the corresponding bornyl acetates. The use of readily accessible chiral starting materials and lactone-lactone rearrangement are the highlights of the present synthesis. The biological activities of the two enantiomers and racemic mixture were tested in a New Zealand vineyard. The (S) (+)-enantiomer was significantly more attractive to P. longispinus males than the racemic mixture or the (R)-(-)-enantiomer. PMID- 26154580 TI - Direct observation of catalytic oxidation of particulate matter using in situ TEM. AB - The ability to observe chemical reactions at the molecular level convincingly demonstrates the physical and chemical phenomena occurring throughout a reaction mechanism. Videos obtained through in situ transmission electron microscopy (TEM) revealed the oxidation of catalytic soot under practical reaction conditions. Carbon oxidation reactions using Ag/SiO2 or Cs2CO3/nepheline catalysts were performed at 330 degrees C under an O2 flow of 0.5 Pa in the TEM measurement chamber. Ag/SiO2 catalyzed the reaction at the interface of the mobile Ag species and carbon, while the Cs species was fixed on the nepheline surface during the reaction. In the latter case, carbon particles moved, remained attached to the Cs2CO3/nepheline surface, and were consumed at the interface by the oxidation reaction. Using this technique, we were able to visualize such mobile and immobile catalysis according to different mechanisms. PMID- 26154582 TI - The Role of CD8 T Cells in Amodiaquine-Induced Liver Injury in PD1-/- Mice Cotreated with Anti-CTLA-4. AB - The mechanism of idiosyncratic drug-induced liver injury (IDILI) remains poorly understood, in part due to the lack of a valid animal model. Clinical evidence suggests that most IDILI is immune mediated, and the major factor preventing liver injury in most patients is immune tolerance. Many attempts have been made in the past to develop an animal model of IDILI, but none had characteristics similar to those of IDILI in humans, and presumably they involved a different mechanism. Recently our laboratory reported a model of amodiaquine (AQ)-induced IDILI using PD1-/- mice and an anti-CTLA4 antibody. This may be the first valid animal model of IDILI because it mimics the characteristics of IDILI in humans. The current study extended the duration of AQ treatment to see if this model would lead to liver failure and to further characterize the associated immune response. Although AQ treatment was extended to 10 weeks and total bilirubin levels were significantly elevated compared to control, there was no further increase from weeks 7 to 10, and the animals did not develop overt liver failure. Mice treated with AQ and anti-CTLA4 had a significant increase in percentage of hepatic CD4, CD8, Th17, and Treg cells after 10 weeks of AQ treatment, as well as significantly decreased NK cells. CD8 T cells have been implicated in several serious idiosyncratic drug reactions, and we used an anti-CD8 antibody to deplete CD8 T cells to study their involvement in this liver injury. We found that depletion of CD8 T cells protected mice from AQ-induced liver injury in this model, which strongly suggests that they are responsible for the liver damage. This is consistent with the finding of CD8 T cells in liver biopsies of human IDILI and may lead the way to an effective treatment for serious IDILI. PMID- 26154583 TI - Selenium supplementation induces mitochondrial biogenesis in trophoblasts. AB - INTRODUCTION: Placental oxidative stress has been implicated in pregnancy complications and previous work has shown that selenium can protect trophoblast mitochondria from oxidative stress. This report examines mitochondrial function and content in trophoblasts supplemented with selenium. METHODS: Swan-71, JEG-3 and BeWo cells and placental tissue were incubated with sodium selenite or selenomethionine. Mitochondrial function was examined in a respirometer. Mitochondrial content was determined using RT-PCR. The levels of the mitochondrial biogenesis markers selenoprotein H, PGC-1alpha and NRF-1 was examined by western blotting. RESULTS: Mitochondrial respiration was significantly enhanced post selenium supplementation in cells and tissues. Selenium supplementation increased mitochondrial content and up-regulated mitochondrial biogenesis mediators in cells. DISCUSSION: These results emphasise the importance of selenium in mitochondrial regeneration in trophoblasts. PMID- 26154584 TI - Does maternal VDR FokI single nucleotide polymorphism have an effect on lead levels of placenta, maternal and cord bloods? AB - INTRODUCTION: Individual susceptibility due to genetic variations appears to be an important factor in lead toxicity. As lead, ubiquitous atmospheric pollutant, behaves very similarly to calcium, gene polymorphisms in proteins involved in calcium homeostasis can affect lead toxicokinetics. Vitamin D receptor (VDR), a DNA-binding transcription factor, activates genes that encode proteins involved in calcium metabolism. Thus, the objective of this study was to determine the effect of maternal VDR FokI polymorphism on lead levels of maternal blood, placental tissue and cord blood. METHODS: The study population comprised 116 women and their respective placenta and umbilical cord. Venous blood samples were drawn from mothers to investigate both the lead levels and VDR FokI polymorphism. Cord blood samples and placentas were collected for lead levels. VDR FokI polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Lead levels were analyzed by dual atomic absorption spectrometer system. RESULTS: Genotype frequencies of VDR FokI polymorphism were 49.2% FF, 44.8% Ff and 6.0% ff. The mean lead levels of maternal blood, placenta and cord blood were 36.76 +/- 13.84 MUg/L, 12.84 +/- 14.47 MUg/kg and 25.69 +/- 11.12 MUg/L, respectively. Maternal blood, placental and cord blood lead levels were found significantly to be higher in mothers with f allele for the VDR FokI polymorphism (p < 0.05). DISCUSSION: The present study indicated that this polymorphism had an effect on maternal and fetal lead levels and that mothers with F allele associated with lower lead concentration may protect their respective fetus against the toxic effects of lead exposure. PMID- 26154585 TI - Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico. AB - The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. PMID- 26154586 TI - (1)H, (13)C, and (15)N backbone resonance assignments of the full-length 40 kDa S. acidocaldarius Y-family DNA polymerase, dinB homolog. AB - The dinB homolog (Dbh) is a member of the Y-family of translesion DNA polymerases, which are specialized to accurately replicate DNA across from a wide variety of lesions in living cells. Lesioned bases block the progression of high fidelity polymerases and cause detrimental replication fork stalling; Y-family polymerases can bypass these lesions. The active site of the translesion synthesis polymerase is more open than that of a replicative polymerase; consequently Dbh polymerizes with low fidelity. Bypass polymerases also have low processivity. Short extension past the lesion allows the high-fidelity polymerase to switch back onto the site of replication. Dbh and the other Y-family polymerases have been used as structural models to investigate the mechanisms of DNA polymerization and lesion bypass. Many high-resolution crystal structures of Y-family polymerases have been reported. NMR dynamics studies can complement these structures by providing a measure of protein motions. Here we report the (15)N, (1)H, and (13)C backbone resonance assignments at two temperatures (35 and 50 degrees C) for Sulfolobus acidocaldarius Dbh polymerase. Backbone resonance assignments have been obtained for 86 % of the residues. The polymerase active site is assigned as well as the majority of residues in each of the four domains. PMID- 26154587 TI - Thermodynamic Relationships with Processivity in Serratia marcescens Family 18 Chitinases. AB - The enzymatic degradation of recalcitrant polysaccharides is accomplished by synergistic enzyme cocktails of glycoside hydrolases (GHs) and accessory enzymes. Many GHs are processive which means that they remain attached to the substrate in between subsequent hydrolytic reactions. Chitinases are GHs that catalyze the hydrolysis of chitin (beta-1,4-linked N-acetylglucosamine). Previously, a relationship between active site topology and processivity has been suggested while recent computational efforts have suggested a link between the degree of processivity and ligand binding free energy. We have investigated these relationships by employing computational (molecular dynamics (MD)) and experimental (isothermal titration calorimetry (ITC)) approaches to gain insight into the thermodynamics of substrate binding to Serratia marcescens chitinases ChiA, ChiB, and ChiC. We show that increased processive ability indeed corresponds to more favorable binding free energy and that this likely is a general feature of GHs. Moreover, ligand binding in ChiB is entropically driven; in ChiC it is enthalpically driven, and the enthalpic and entropic contributions to ligand binding in ChiA are equal. Furthermore, water is shown to be especially important in ChiA-binding. This work provides new insight into oligosaccharide binding, getting us one step closer to understand how GHs efficiently degrade recalcitrant polysaccharides. PMID- 26154589 TI - Hierarchical, Ultrathin Single-Crystal Nanowires of CdS Conveniently Produced in Laser-Induced Thermal Field. AB - Hierarchical nanowires (HNWs) exhibit unique properties and have wide applications, while often suffering from imperfect structure. Herein, we report a facile strategy toward ultrathin CdS HNWs with monocrystal structure, where a continuous-wave (CW) Nd:YAG laser is employed to irradiate an oleic acid (OA) solution containing precursors and a light absorber. The high heating rate and large temperature gradient generated by the CW laser lead to the rapid formation of tiny zinc-blende CdS nanocrystals which then line up into nanowires with the help of OA molecules. Next, the nanowires experience a phase transformation from zinc-blende to wurtzite structure, and the transformation-induced stress creates terraces on their surface, which promotes the growth of side branches and eventually results in monocrystal HNWs with an ultrathin diameter of 24 nm. The one-step synthesis of HNWs is conducted in air and completes in just 40 s, thus being very simple and rapid. The prepared CdS HNWs display photocatalytic performance superior to their nanoparticle counterparts, thus showing promise for catalytic applications in the future. PMID- 26154588 TI - Somatic ATP2A2 mutation in a case of papular acantholytic dyskeratosis: mosaic Darier disease. AB - Papular acantholytic dyskeratosis, also known as acantholytic dermatosis of the vulvocrural (or anogenital) area, is an uncommon eruption reported predominantly in women. This entity manifests with pruritic papules in the groin/anogenital area and less commonly on the chest. The pathobiology of papular acantholytic dyskeratosis is uncertain. A 62-year-old woman presented with multiple verrucous appearing lesions in the groin and on the chest showing acantholytic dyskeratosis on histopathology. Given histological similarity of these papular acantholytic dyskeratosis lesions to Darier disease due to inherited ATP2A2 mutation, we screened affected and normal tissue and peripheral blood in our patient for mutations in ATP2A2. We found an identical ATP2A2 p.706D>N mutation in multiple independent papular acantholytic dyskeratosis lesions that was not present in uninvolved skin or peripheral blood DNA. These findings establish somatic mosaicism of ATP2A2 mutations as a genetic cause for papular acantholytic dyskeratosis. PMID- 26154590 TI - Orbital Myositis as Both a Presenting and Associated Extraintestinal Sign of Crohn's Disease. AB - Orbital myositis is a rare extraintestinal manifestation of inflammatory bowel disease and has been reported to occur at variable times relative to gastrointestinal symptoms, including years before, concurrently to, and years after the gastrointestinal diagnosis. Here, the authors report 3 cases of Crohn's disease associated orbital myositis, adding to the 18 previously reported cases. The authors describe 2 cases of middle-aged females presenting with orbital myositis during clinical remission of Crohn's disease. The authors also describe the first reported case of orbital myositis-associated Crohn's disease diagnosed prior to any gastrointestinal symptoms in a teenage male presenting with corticosteroid responsive intermittent eyelid swelling. These cases underscore the importance of the Ophthalmic Plastic Surgeon in initiating a thorough systemic workup for cases of orbital inflammatory disease. PMID- 26154591 TI - Pyrene-end-functionalized poly(L-lactide) as an efficient carbon nanotube dispersing agent in poly(L-lactide): mechanical performance and biocompatibility study. AB - In order to improve the mechanical properties of poly(L-lactide) (PLLA) based implants, a study was made of how far well dispersed multi-walled carbon nanotubes (MWCNTs) within a PLLA matrix were able to positively affect these properties. To this end, pyrene-end-functionalized poly(L-lactide) (py-end-PLLA) was evaluated as a dispersing agent. Transmission electron microscopy (TEM) analyses and mechanical tests of MWCNTs-based materials demonstrated an enhancement of MWCNT dispersion in the PLLA matrix and improved Young's modulus (E) when 4 wt% of py-end-PLLA was used as the dispersing agent. Subsequently, the bioacceptance of PLLA/py-end-PLLA/MWCNTs nanocomposites was evaluated using human bone marrow stromal cells (HBMC) in vitro. The inclusion of py-end-PLLA and MWCNTs supported HBMC adhesion and proliferation. The expression levels of the bone-specific markers indicated that the cells kept their potential to undergo osteogenic differentiation. The results of this study indicate that the addition of MWCNT combined with py-end-PLLA in PLLA/py-end-PLLA/MWCNTs nanocomposites may widen the range of applications of PLLA within the field of bone tissue engineering thanks to their mechanical strength and cytocompatibility. PMID- 26154593 TI - Predation on heterospecific larvae by adult females of Kampimodromus aberrans, Amblyseius andersoni, Typhlodromus pyri and Phytoseius finitimus (Acari: Phytoseiidae). AB - The predatory mites Kampimodromus aberrans (Oudemans), Amblyseius andersoni (Chant), Typhlodromus pyri Scheuten and Phytoseius finitimus Ribaga are important biological control agents in orchards and vineyards in Europe and elsewhere. They can coexist in the same habitat and engage in intraguild predation (IGP). In the laboratory we evaluated the longevity, fecundity and prey consumption of females of these predatory mites fed with heterospecific larvae considered as intraguild prey (IG-prey). The survival and age-specific oviposition curves of predatory mites fed with pollen were compared with those obtained on different IG-prey. We assessed the prey conversion rate into eggs expressed by the different IG predator as an indicator of their capacity to persist when prey is diminishing. Results suggest that A. andersoni should be considered the superior intraguild predator but the least efficient in food conversion. Phytoseius finitimus appeared to suffer from intraguild predation, and its efficiency in food conversion was not superior to that of K. aberrans and T. pyri. The profiles of K. aberrans and T. pyri were less definite. The comparison between pollen and IG prey diets confirmed the positive effect of pollen on the fecundity of all four predatory mite species. Fecundity was higher on pollen than on IG-prey. We can suggest that A. andersoni have the potential to exclude the other predatory mites only at high food resource availability, whereas low levels of food availability can favor the other species in IGP. PMID- 26154596 TI - NaSrCo2F7, a Co(2+) pyrochlore antiferromagnet. AB - We report the crystal growth, by the Bridgeman-Stockbarger method, and the basic magnetic properties of a new cobalt-based pyrochlore, NaSrCo2F7. Single-crystal structure determination shows that Na and Sr are completely disordered on the non magnetic large atom A sites, while magnetic [Formula: see text] Co(2+) fully occupies the pyrochlore lattice B sites. NaSrCo2F7 displays strong antiferromagnetic interactions ([Formula: see text]), a large effective moment ([Formula: see text]), and no spin freezing until 3 K. Thus, NaSrCo2F7 is a geometrically frustrated antiferromagnet with a frustration index [Formula: see text]. Ac susceptibility, dc susceptibility, and heat capacity are utilized to characterize the spin freezing. We argue that NaSrCo2F7 and the related material NaCaCo2F7 are examples of frustrated pyrochlore antiferromagnets with weak bond disorder. PMID- 26154597 TI - Understanding Human Mobility from Twitter. AB - Understanding human mobility is crucial for a broad range of applications from disease prediction to communication networks. Most efforts on studying human mobility have so far used private and low resolution data, such as call data records. Here, we propose Twitter as a proxy for human mobility, as it relies on publicly available data and provides high resolution positioning when users opt to geotag their tweets with their current location. We analyse a Twitter dataset with more than six million geotagged tweets posted in Australia, and we demonstrate that Twitter can be a reliable source for studying human mobility patterns. Our analysis shows that geotagged tweets can capture rich features of human mobility, such as the diversity of movement orbits among individuals and of movements within and between cities. We also find that short- and long-distance movers both spend most of their time in large metropolitan areas, in contrast with intermediate-distance movers' movements, reflecting the impact of different modes of travel. Our study provides solid evidence that Twitter can indeed be a useful proxy for tracking and predicting human movement. PMID- 26154592 TI - Antioxidants in Translational Medicine. AB - SIGNIFICANCE: It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. RECENT ADVANCES: The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. CRITICAL ISSUES: Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. FUTURE DIRECTIONS: Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities. PMID- 26154598 TI - Postoperative Surveillance and Long-term Outcomes After Endovascular Aneurysm Repair Among Medicare Beneficiaries. AB - IMPORTANCE: The Society for Vascular Surgery recommends annual surveillance with computed tomography (CT) or ultrasonography after endovascular aortic aneurysm repair (EVAR) for abdominal aortic aneurysms. However, such lifelong surveillance may be unnecessary for most patients, thereby contributing to overuse of imaging services. OBJECTIVE: To investigate whether nonadherence to Society for Vascular Surgery-recommended surveillance guidelines worsens long-term outcomes after EVAR among Medicare beneficiaries. DESIGN, SETTING, AND PARTICIPANTS: We collected data from Medicare claims from January 1, 2002, through December 31, 2011. A total of 9503 patients covered by fee-for-service Medicare who underwent EVAR from January 1, 2002, through December 31, 2005, were categorized as receiving complete or incomplete surveillance. We performed logistic regressions controlling for patient demographic and hospital characteristics. Patients were then matched by propensity score with adjusting for all demographic variables, including age, sex, race, Medicaid eligibility, residential status, hospital volume, ruptured abdominal aortic aneurysms, and all preexisting comorbidities. We then calculated differences in long-term outcomes after EVAR between adjusted groups. Data analysis was performed from January 1, 2002, through December 31, 2011. MAIN OUTCOMES AND MEASURES: Post-EVAR imaging modality, aneurysm-related mortality, late rupture, and complications. RESULTS: Median follow-up duration was 6.1 years. Incomplete surveillance was observed in 5526 of 9695 patients (57.0%) who survived the initial hospital stay at a mean (SD) of 5.2 (2.9) years after EVAR. After propensity matching, our cohort consisted of 7888 patients, among whom 3944 (50.0%) had incomplete surveillance. For those in the matched cohort, patients with incomplete surveillance had a lower incidence of late ruptures (26 of 3944 [0.7%] vs 57 of 3944 [1.4%]; P = .001) and major or minor reinterventions (46 of 3944 [1.2%] vs 246 of 3944 [6.2%]; P < .001) in unadjusted analysis. Aneurysm-related mortality was not statistically different between groups (13 of 3944 [0.3%] vs 24 of 3944 [0.6%]; P = .07). In adjusted analysis of postoperative outcomes controlling for all patient and hospital factors by the tenth postoperative year, patients in the incomplete surveillance group experienced lower rates of total complications (2.1% vs 14.0%; P < .001), late rupture (1.1% vs 5.3%; P < .001), major or minor reinterventions (1.4% vs 10.0%; P < .001), aneurysm-related mortality (0.4% vs 1.3%; P < .001), and all-cause mortality (30.9% vs 68.8%, P < .001). CONCLUSIONS AND RELEVANCE: Nonadherence to the Society for Vascular Surgery guidelines for post-EVAR imaging was not associated with poor outcomes, suggesting that, in many patients, less frequent surveillance is not associated with worse outcomes. Improved criteria for defining optimal surveillance will achieve higher value in aneurysm care. PMID- 26154599 TI - Reproductive biology and nectar production of the Mexican endemic Psittacanthus auriculatus (Loranthaceae), a hummingbird-pollinated mistletoe. AB - Many mistletoe species produce 'bird'-pollinated flowers; however, the reproductive biology of the majority of these species has not been studied. Psittacanthus auriculatus is a Mexican endemic mistletoe, most common in open, dry mesquite grassland. Knowledge of the reproductive biology of P. auriculatus is essential for understanding species formation and diversification of Psittacanthus mistletoes, but it is currently poorly understood. Thus, we studied floral biology and phenology, nectar production and breeding system and pollination of this species. The hermaphroditic red-pink flowers open from the middle to the tip and petals are curly, but remain partially fused forming a floral tube of ca. 20-mm long. Flowers are partially protandrous, produce large amounts of nectar, last 2 days, and stigma receptivity is highest during the second day. We recorded hummingbirds (Cynanthus latirostris, Hylocharis leucotis, Amazilia beryllina, A. violiceps, Calothorax lucifer, Archilochus colubris) and less commonly butterflies (Agraulis vanillae, Anteos clorinde, Papilio multicaudatus, Phocides urania, Phoebis sennae) as floral visitors. P. auriculatus flowers are self-compatible. However, this mistletoe is an obligate animal-pollinated species, as the sensitive stigma avoids self-pollination. Under natural conditions, reproductive success was higher than in manually selfed or cross-pollinated flowers, likely due to the traplining foraging behaviour of hummingbirds. We suggest that the apparent efficient foraging behaviour of hummingbirds maintains gene flow among P. auriculatus, promoting outcrossing. PMID- 26154601 TI - EDITORIAL. PMID- 26154600 TI - Abnormalities in the T cell receptor Vdelta repertoire and Foxp3 expression in refractory anemia with ringed sideroblasts. AB - Immune dysregulation has been implicated in myelodysplastic syndrome (MDS) pathogenesis. Refractory anemia with ringed sideroblasts (RARS) is a low-risk subtype of MDS. Our previous study has reported an abnormal gammadelta T cell receptor (TCR) repertoire in patients with intermediate or high-risk MDS. To characterize the status of T cell immunity in RARS, we investigated the distribution and clonality of the TCR Vdelta repertoire and the expression of Foxp3 in patients with RARS. The number of expressed Vdelta subfamily members in the RARS group (4.8+/-2.25) was significantly lower than that in the control group (7.6+/-0.52, p=0.0012). A significantly lower expression frequency for the Vdelta4 (p=0.007), Vdelta5 (p=0.0049) and Vdelta7 subfamilies (p=0.0225) could be detected in the RARS group. The most frequent clonally expanded T cell subfamily member in the RARS group was Vdelta7 (100%, 3/3). Foxp3 mRNA expression was significantly lower and higher than that in the controls in 60% and 40% RARS patients, respectively. In conclusion, marked restriction of the TCR Vdelta subfamily expression pattern and great heterogeneity in Foxp3 expression were characteristics found in RARS. These results provide data regarding the immunodeficiency and immune reactive characteristics of patients with RARS, which may provide a basis for immunotherapy options. PMID- 26154602 TI - Directing positional specificity in enzymatic synthesis of bioactive 1 phosphatidylinositol by protein engineering of a phospholipase D. AB - Phosphatidylinositol (PI) holds a potential of becoming an important dietary supplement due to its effects on lipid metabolism in animals and humans manifested as a decrease of the blood cholesterol and lipids, and relief of the metabolic syndrome. To establish an efficient, enzymatic system for PI production from phosphatidylcholine and myo-inositol as an alcohol acceptor, our previous study started with the wild-type Streptomyces antibioticus phospholipase D (SaPLD) as a template for generation of PI-synthesizing variants by saturation mutagenesis targeting positions involved in acceptor accommodation, W187, Y191, and Y385. The isolated variants generated PI as a mixture of positional isomers, among which only 1-PI exists in nature. Thus, the current study has focused to improve positional specificity of W187N/Y191Y/Y385R SaPLD (NYR) which generates PI as a mixture of 1-PI and 3-PI in the ratio of 76/24, by subjecting four residues of its acceptor-binding site to saturation mutagenesis. Subsequent screening pointed at NYR-186T and NYR-186L as the most improved variants producing PI with a ratio of 1-/3-PI = 93/7 and 87/13, respectively, at 37 degrees C. Lowering the reaction temperature further improved the specificity of both variants to 1-/3-PI > 97/3 at 20 degrees C with no change in total PI yield. Structure model analyses imply that G186T and G186L mutations increased rigidity of the acceptor-binding site, thus limiting the possible orientations of myo inositol. The two newly isolated PLDs are promising for future application in large-scale 1-PI production. PMID- 26154603 TI - Green Synthesis of Fluorescent Carbon Dots for Selective Detection of Tartrazine in Food Samples. AB - A simple, economical, and green method for the preparation of water-soluble, high fluorescent carbon quantum dots (C-dots) has been developed via hydrothermal process using aloe as a carbon source. The synthesized C-dots were characterized by atomic force microscope (AFM), transmission electron microscopy (TEM), fluorescence spectrophotometer, UV-vis absorption spectra as well as Fourier transform infrared spectroscopy (FTIR). The results reveal that the as-prepared C dots were spherical shape with an average diameter of 5 nm and emit bright yellow photoluminescence (PL) with a quantum yield of approximately 10.37%. The surface of the C-dots was rich in hydroxyl groups and presented various merits including high fluorescent quantum yield, excellent photostability, low toxicity and satisfactory solubility. Additionally, we found that one of the widely used synthetic food colorants, tartrazine, could result in a strong fluorescence quenching of the C-dots through a static quenching process. The decrease of fluorescence intensity made it possible to determine tartrazine in the linear range extending from 0.25 to 32.50 MUM, This observation was further successfully applied for the determination of tartrazine in food samples collected from local markets, suggesting its great potential toward food routine analysis. Results from our study may shed light on the production of fluorescent and biocompatible nanocarbons due to our simple and environmental benign strategy to synthesize C dots in which aloe was used as a carbon source. PMID- 26154604 TI - Natural variation in timing of stress-responsive gene expression predicts heterosis in intraspecific hybrids of Arabidopsis. AB - The genetic distance between hybridizing parents affects heterosis; however, the mechanisms for this remain unclear. Here we report that this genetic distance correlates with natural variation and epigenetic regulation of circadian clock mediated stress responses. In intraspecific hybrids of Arabidopsis thaliana, genome-wide expression of many biotic and abiotic stress-responsive genes is diurnally repressed and this correlates with biomass heterosis and biomass quantitative trait loci. Expression differences of selected stress-responsive genes among diverse ecotypes are predictive of heterosis in their hybrids. Stress responsive genes are repressed in the hybrids under normal conditions but are induced to mid-parent or higher levels under stress at certain times of the day, potentially balancing the tradeoff between stress responses and growth. Consistent with this hypothesis, repression of two candidate stress-responsive genes increases growth vigour. Our findings may therefore provide new criteria for effectively selecting parents to produce high- or low-yield hybrids. PMID- 26154606 TI - Species-specific responses to island connectivity cycles: refined models for testing phylogeographic concordance across a Mediterranean Pleistocene Aggregate Island Complex. AB - The contribution of Pleistocene sea level changes to diversification patterns in archipelagos around the world, and specifically whether the repeated cycles of island connectivity and isolation acted as a 'species pump' is debated. The debate has been perpetuated in part because of the type of evidence used to evaluate the species-pump hypothesis. Specifically, existing tests of the 'Pleistocene Aggregate Island Complex' (PAIC) model of diversification interpret the lack of concordant divergence times among multiple codistributed taxa as a rejection of the PAIC model. However, the null expectation of concordance disregards taxon-specific ecological traits and geographic characteristics that may affect population persistence and gene flow among islands. Here, we study the factors affecting population divergence in thirteen flightless darkling beetle species (Coleoptera: Tenebrionidae) across the PAIC system of the Cycladic plateau in the Aegean archipelago. Based on isolation-by-resistance analyses, hierarchical amova and the degree of genealogical sorting on individual islands, we identify a major effect of bathymetry and habitat stability on the levels of genetic divergence across the PAIC, with island size and body size playing a secondary role as well. We subsequently use bathymetric maps and habitat association to generate predictions about the set of islands and group of taxa expected to show phylogeographic concordance. We test these predictions using hierarchical approximate Bayesian computation and show how our interpretations regarding the role of PAICs as drivers of divergence change when relying on a null expectation of concordance compared to a refined model that takes geography and ecological traits into account. PMID- 26154605 TI - Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk. AB - The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention. PMID- 26154607 TI - Bacterial Infection and Immune Responses in Lutzomyia longipalpis Sand Fly Larvae Midgut. AB - The midgut microbial community in insect vectors of disease is crucial for an effective immune response against infection with various human and animal pathogens. Depending on the aspects of their development, insects can acquire microbes present in soil, water, and plants. Sand flies are major vectors of leishmaniasis, and shown to harbor a wide variety of Gram-negative and Gram positive bacteria. Sand fly larval stages acquire microorganisms from the soil, and the abundance and distribution of these microorganisms may vary depending on the sand fly species or the breeding site. Here, we assess the distribution of two bacteria commonly found within the gut of sand flies, Pantoea agglomerans and Bacillus subtilis. We demonstrate that these bacteria are able to differentially infect the larval digestive tract, and regulate the immune response in sand fly larvae. Moreover, bacterial distribution, and likely the ability to colonize the gut, is driven, at least in part, by a gradient of pH present in the gut. PMID- 26154608 TI - Facile Preparation of alpha-Cyano-alpha,omega-Diaryloligovinylenes: A New Class of Color-Tunable Solid Emitters. AB - An efficient Knoevenagel condensation reaction was used to construct a series of alpha-cyano-alpha,omega-diaryloligovinylenes, which show prominent fluorescence emission in the solid state. On investigating the effect of conjugation length on fluorescent properties, we found that the diene structure showed superior solid state luminescence. Furthermore, the emission color could be adjusted by introducing donor or acceptor functional groups at the terminal aryl groups. Full color emission in the visible region can be achieved by adding different functional groups to the alpha-cyano-alpha,omega-diaryldivinylene moiety. The structure-property relationships were elucidated and some observations such as the substitution position effects were discussed. These compounds have potential applications as full-color solid emissive candidates in material science and their simple structures allow them to be easily modified resulting in further interesting properties. PMID- 26154609 TI - The change in platelet count in patients with acute coronary syndrome 6 months after coronary stent implantation. AB - After coronary stent implantation, patients with acute coronary syndrome commonly take clopidogrel, and few patients develop severe thrombocytopenia related to clopidogrel. However, we found in our clinical practice that platelet counts of most patients decrease slightly after taking clopidogrel for 6 months. To address this discrepancy, we studied the change in platelet count after coronary stent implantation in patients with acute coronary syndrome. Ninety-five patients were selected for this study, and their pre-stent platelet counts were compared with those 6 months after stent implantation. All patients had low/intermediate-risk non-ST segment elevation myocardial infarction/unstable angina and underwent delayed coronary interventional treatment. No patient suffered from thrombocytopenia (<100 * 10/l) during the 6-month observation period. Six months after stent implantation, platelet counts significantly decreased in the majority of patients (73/95, 76.9%) and increased only in the minority of patients (22/95, 23.1%). A multivariate analysis showed that the change in platelet count was positively correlated with the change in leukocyte and fibrinogen value, and negatively correlated with number of stents. The platelet count decreased in the majority of patients after stent implantation, which may be caused by the removal of stress factors or stent-related platelet consumption. Clopidogrel may partly prevent stent-related platelet consumption. PMID- 26154610 TI - Venous stasis and whole blood platelet aggregometry: a question of data reliability and patient safety. AB - The assessment of platelet function by multiple electrode aggregometry (MEA) (Multiplate, Roche Diagnostics GmbH) is common in laboratory hematology. As regards the ISO 15189:2012 international standard, appropriate use of laboratory equipment requires appropriate pre-examination activities (e.g., blood collection). Venous stasis can influence several blood analytes, but the tourniquet time is rarely regarded as a source of variability. Aim of the present study was to evaluate the impact of venous stasis on platelet function by MEA. A total of 6 ml of blood was collected from 20 volunteers into two 3.0 ml Hirudin vacuum tube (Roche Diagnostics GmbH), and subjected to two procedures: procedure 1 (no stasis) - collection after localization of forearm vein by subcutaneous tissue transilluminator device without tourniquet; procedure 2 (stasis) - collection after localization of vein by prior 60 s tourniquet application. Samples were processed on Multiplate, for: ADP-test (without prostaglandin E1), ADP HS-test (with prostaglandin E1), ASPI-test, COL-test, RISTO H-test (high concentration, 0.77 mg/ml), RISTO L-test (low concentration, 0.20 mg/ml), and TRAP-test. The significance of the differences between samples was assessed by Wilcoxon ranked-pairs test. Surprisingly, the results of ADP HS-test, ASPI-test, COL-test, and RISTO H-test appeared unbiased by venous stasis. RISTO L-test, ADP test, and TRAP-test were significantly biased; the mean percent difference between stasis and no stasis were -7.2% (P = 0.040), -28.4% (P = 0.015), and 1.1% (P = 0.031), respectively. In conclusion, the tourniquet should be avoided when assessing platelet function by MEA. PMID- 26154611 TI - Thrombosis secondary to acute hypernatraemia after liver hydatid cyst surgery. AB - Hypernatraemia after hypertonic saline irrigation of a hepatitic hydatid cyst is a rare but serious complication. Neurological symptoms and signs are frequently seen in hypernatraemia. However, other symptoms, such as fever, acute pulmonary oedema, congestive cardiac failure and muscular alterations, may appear. It has recently been suggested that hypernatraemia increases the risk of thrombosis.We present the first report of an adult patient who survived a severe acute iatrogenic hypernatraemia and hyper-coagulability resulting from hypertonic saline irrigation of intra-abdominal hydatid cysts. PMID- 26154612 TI - Use of apixaban after development of suspected rivaroxaban-induced hepatic steatosis; a case report. AB - Postmarketing reports have emerged associating rivaroxaban with drug-induced liver injury (DILI); however, management strategies of patients with suspected rivaroxaban-induced liver injury requiring continued anticoagulation have not been published. The present report describes a 67-year-old male with atrial fibrillation receiving rivaroxaban who developed a 16-fold elevation in alanine transaminase, a nearly two-fold elevation in total bilirubin, and ultrasound confirmed hepatic steatosis. The patient was switched from rivaroxaban to apixaban with subsequent rapid resolution of laboratory abnormalities. Rapid improvement in liver function tests despite use of an alternative factor Xa inhibitor suggests that rivaroxaban's mechanism of hepatotoxicity may be unrelated to its pharmacologic action. When using rivaroxaban, clinicians should be aware of the small but potentially serious risk of DILI. Because most anticoagulants have been associated with DILI, selection of an alternative anticoagulant may be challenging; however, the use of apixaban in this case suggests it may be a reasonable alternative. PMID- 26154613 TI - Expedient and Divergent Tandem One-Pot Synthesis of Benz[e]indole and Spiro[indene-1,3'-pyrrole] Derivatives from Alkyne-Tethered Chalcones/Cinnamates and TosMIC. AB - An efficient solvent-dependent regioselective [3 + 2] cycloaddition/iodocyclization cascade reaction of alkyne-tethered chalcones/cinnamates and TosMIC has been developed. The reaction represents a novel protocol for the expedient and divergent one-pot synthesis of benz[e]indoles and spiro[indene-1,3'-pyrroles] from acyclic common precursors at room temperature. PMID- 26154614 TI - Initial testing (stage 1) of the anti-microtubule agents cabazitaxel and docetaxel, by the pediatric preclinical testing program. AB - BACKGROUND: Although microtubule-destabilizing agents (principally vincristine) are in common use in pediatric oncology, the microtubule-stabilizing taxanes are uncommonly used to treat childhood cancers. Cabazitaxel has been reported to have activity superior to that of docetaxel in preclinical models of multidrug resistant adult cancers, and it was active in patients who had progressed on or after docetaxel. The PPTP conducted a comparison of these two agents against the PPTP in vitro panel and against a limited panel of solid tumor xenografts. PROCEDURES: Cabazitaxel and docetaxel were tested against the PPTP in vitro cell line panel at concentrations from 0.01 to 0.1 MUM and in vivo against a subset of the PPTP solid tumor xenograft models at a dose of 10 or 7.5 mg/kg on an every 4 days * 3 I.V. schedule. RESULTS: In vitro, both cabazitaxel and docetaxel had similar potency (median rIC50 0.47 nM and 0.88 nM, respectively) and a similar activity profile, with Ewing sarcoma cells being significantly more sensitive to both agents. In vitro sensitivity to docetaxel inversely correlated with mRNA expression for ABCB1, but the correlation with ABCB1 expression was weaker for cabazitaxel. In vivo cabazitaxel demonstrated significantly greater activity than docetaxel in five of 12 tumor models, inducing regressions in six models compared with three models for docetaxel. CONCLUSIONS: Cabazitaxel demonstrated superior activity compared to docetaxel. The lower cabazitaxel systemic exposure tolerated in humans compared to mice needs to be considered when extrapolating these results to the clinical setting. PMID- 26154615 TI - The Mechanism of Ca(2+) Movement in the Involvement of Baicalein-Induced Cytotoxicity in ZR-75-1 Human Breast Cancer Cells. AB - Baicalein (5,6,7-trihydroxyflavone) (1) has been found to be active against a wide variety of cancer cells. However, the molecular mechanism underlying the effects of 1 on the induction of Ca(2+) movement and cytotoxicity in human breast cancer cells is unknown. This study examined the relationship between 1-induced Ca(2+) signaling and cytotoxicity in ZR-75-1 human breast cancer cells. The in vitro investigations reported herein produced the following results: (i) Compound 1 increased intracellular Ca(2+) concentration ([Ca(2+)]i) in a concentration dependent manner. The signal was decreased by approximately 50% by removal of extracellular Ca(2+). (ii) Compound 1-triggered [Ca(2+)]i increases were significantly suppressed by store-operated Ca(2+) channel blockers 2 aminoethoxydiphenyl borate (2-APB) and the PKC inhibitor GF109203X. (iii) In Ca(2+)-free medium, compound 1-induced [Ca(2+)]i increases were also inhibited by GF109203X. Furthermore, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-ditert-butylhydroquinone (BHQ) abolished 1 induced [Ca(2+)]i increases. Inhibition of phospholipase C (PLC) with U73122 abolished 1-induced [Ca(2+)]i increases. (iv) Compound 1 (20-40 MUM) caused cytotoxicity, increased reactive oxygen species (ROS) production, and activated caspase-9/caspase-3. Furthermore, compound 1-induced apoptosis was significantly inhibited by prechelating cytosolic Ca(2+) with BAPTA-AM (1,2-bis(2 aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester) or by decreasing ROS with the antioxidant NAC (N-acetylcysteine). Together, baicalein (1) induced a [Ca(2+)]i increase by inducing PLC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via PKC-dependent, 2-APB-sensitive store-operated Ca(2+) channels. Moreover, baicalein (1) induced Ca(2+)-associated apoptosis involved ROS production in ZR-75-1 cells. PMID- 26154616 TI - Maleimide fused boron-fluorine complexes: synthesis, photophysical and electrochemical properties. AB - Novel boron fluorine complex molecules were designed and synthesized using the maleimide core moiety. Significant features such as a large Stoke shift, high quantum yield, and long range absorption and emission wavelengths were observed for these molecules. The lower LUMO level of these molecules indicates their potential application as electron transport materials. The optical band gap was calculated and compared by using UV-absorption edge, density functional theory and electrochemical studies, revealing the charge transfer characteristics. PMID- 26154617 TI - Lymph Node Metastasis, a Unique Independent Prognostic Factor in Early Gastric Cancer. AB - BACKGROUND: Lymph node metastasis (LNM) has been shown to be related to the prognosis of early gastric cancer (EGC). The choice of optimal treatment depends on an accurate pre-operative assessment of LNM status in EGC patients. However, in China, where EGC cases account for only a small part of gastric cancer (GC) cases, there are not enough data to make an accurate assessment. Therefore, this study, which involved a relatively large number of EGC patients, aimed to explore the relationship between clinicopathological characteristics and LNM in EGC. METHODS: Clinicopathological data from 205 EGC patients who underwent surgical resection at Sun Yat-Sen University Cancer Center from January 2000 to December 2011 were retrospectively analyzed. Clinicopathological characteristics were assessed to identify effective predictive factors for LNM and overall survival. RESULTS: LNM occurred in 52 (25.37%) EGC cases; of these cases, 18 occurred in intra-mucosal cancers (13 N1, 4 N2 and 1 N3), and 34 occurred in sub-mucosal cancers (22 N1, 7 N2 and 5 N3). Logistic regression analysis demonstrated that tumor differentiation (P=0.002), depth of tumor infiltration (P=0.004), vessel invasion (P=0.012), tumor size (P=0.020) and gender (P=0.022) were risk factors associated with LNM in EGC, listed in order of priority. The overall survival rate was 90.2%. Kaplan-Meier survival analysis showed that overall survival of EGC patients was significantly correlated with LNM (P=0.001), N staging (P<0.001) and invasion of lymphatic or blood vessels (P=0.010), but it was not correlated with tumor size, depth of tumor infiltration or tumor cell differentiation. Moreover, a multiple Cox regression analysis demonstrated that only N staging (P=0.001) could serve as an independent prognostic predictor in EGC patients. CONCLUSIONS: Because LNM independently predicts the prognosis of EGC, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) and laparoscopic partial gastrectomy should be cautiously used in high-risk EGC patients. A pre-operative assessment of LNM status based on clinicopathological factors may be useful for therapy planning. PMID- 26154618 TI - A multicenter randomized study to evaluate intracoronary abciximab with the ClearWay catheter to improve outcomes with Lysis (IC ClearLy): trial study design and rationale: Erratum. AB - [This corrects the article on p. 529-535 in vol. 11, issue 7, PMID: 19918189. Ducci CB should have appeared as Bucciarelli-Ducci C.]. PMID- 26154619 TI - On-surface photo-dissociation of C-Br bonds: towards room temperature Ullmann coupling. AB - The surface-assisted synthesis of gold-organometallic hybrids on the Au(111) surface both by thermo- and light-initiated dehalogenation of bromo-substituted tetracene is reported. Combined X-ray photoemission (XPS) and scanning tunneling microscopy (STM) data reveal a significant increase of the surface order when mild reaction conditions are combined with 405 nm light irradiation. PMID- 26154620 TI - Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years. AB - Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 * 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids. PMID- 26154621 TI - Obesity in Preschool-Aged Children with Sickle Cell Anemia: Emerging Nutritional Challenge in a Resource Limited Setting. AB - BACKGROUND: The burden of childhood obesity is increasing in most developing countries particularly in the urban areas owing to globalization; and children with sickle cell anemia (SCA) in such environment do not live in isolation. The study is aimed at determining the prevalence of obesity in younger children with SCA. METHODS: A consecutive recruitment of 58 children with SCA aged between 1 year and 5 years 4 months (subjects) and their age and sex matched controls selected using multistage sampling technique were carried out. The weight and height of the children were obtained using standard equipment. The WHO Anthro and Anthro-Plus software were used for analyzing the nutritional status of the children based on standard deviation (z-scores). The data were analyzed using SPSS version 19.0 while the level of significance was set at p < 0.05. RESULTS: The mean BMI for the subjects was 15.38 +/- 1.93 (range from 11.50-20.80) and 17.10 +/- 2.28 (range from 13.4-23.20) in the controls. Overweight (z-score > + 1 <= 2) and obesity (z score >+2) were recorded in 10 (17.2%) and 2 (3.4%) of the subjects while in the controls overweight and obesity were observed in 16 (27.6%) and 13 (22.4%), respectively (p = 0.000). CONCLUSIONS: Obesity and overweight is becoming prevalent among children with SCA and so awareness and preventive health education about obesity should be created among caregivers of children with sickle cell anemia in our setting to avert its possible complications. PMID- 26154622 TI - On Public Influence on People's Interactions with Ordinary Biodiversity. AB - Besides direct impacts of urban biodiversity on local ecosystem services, the contact of city dwellers with urban nature in their everyday life could increase their awareness on conservation issues. In this paper, we focused on a particularly common animal urban species, the feral pigeon Columba livia. Through an observational approach, we examined behavioral interactions between city dwellers and this species in the Paris metropolis, France. We found that most people (mean: 81%) do not interact with pigeons. Further, interactions (either positive or negative) are context and age-dependent: children interact more than adults and the elderly, while people in tourist spots interact more than people in urban parks or in railway stations, a result that suggests that people interacting with pigeons are mostly tourists. We discuss these results in terms of public normative pressures on city dwellers' access to and reconnection with urban nature. We call for caution in how urban species are publically portrayed and managed, given the importance of interactions with ordinary biodiversity for the fate of nature conservation. PMID- 26154623 TI - Size-exclusion chromatography as a stand-alone methodology identifies novel markers in mass spectrometry analyses of plasma-derived vesicles from healthy individuals. AB - Plasma-derived vesicles hold a promising potential for use in biomedical applications. Two major challenges, however, hinder their implementation into translational tools: (a) the incomplete characterization of the protein composition of plasma-derived vesicles, in the size range of exosomes, as mass spectrometric analysis of plasma sub-components is recognizably troublesome and (b) the limited reach of vesicle-based studies in settings where the infrastructural demand of ultracentrifugation, the most widely used isolation/purification methodology, is not available. In this study, we have addressed both challenges by carrying-out mass spectrometry (MS) analyses of plasma-derived vesicles, in the size range of exosomes, from healthy donors obtained by 2 alternative methodologies: size-exclusion chromatography (SEC) on sepharose columns and Exo-SpinTM. No exosome markers, as opposed to the most abundant plasma proteins, were detected by Exo-SpinTM. In contrast, exosomal markers were present in the early fractions of SEC where the most abundant plasma proteins have been largely excluded. Noticeably, after a cross-comparative analysis of all published studies using MS to characterize plasma-derived exosomes from healthy individuals, we also observed a paucity of "classical exosome markers." Independent of the isolation method, however, we consistently identified 2 proteins, CD5 antigen-like (CD5L) and galectin-3-binding protein (LGALS3BP), whose presence was validated by a bead-exosome FACS assay. Altogether, our results support the use of SEC as a stand-alone methodology to obtain preparations of extracellular vesicles, in the size range of exosomes, from plasma and suggest the use of CD5L and LGALS3BP as more suitable markers of plasma-derived vesicles in MS. PMID- 26154624 TI - Effect of Methanethiol Concentration on Sulfur Production in Biological Desulfurization Systems under Haloalkaline Conditions. AB - Bioremoval of H2S from gas streams became popular in recent years because of high process efficiency and low operational costs. To expand the scope of these processes to gas streams containing volatile organic sulfur compounds, like thiols, it is necessary to provide new insights into their impact on overall biodesulfurization process. Published data on the effect of thiols on biodesulfurization processes are scarce. In this study, we investigated the effect of methanethiol on the selectivity for sulfur production in a bioreactor integrated with a gas absorber. This is the first time that the inhibition of biological sulfur formation by methanethiol is investigated. In our reactor system, inhibition of sulfur production started to occur at a methanethiol loading rate of 0.3 mmol L(-1) d(-1). The experimental results were also described by a mathematical model that includes recent findings on the mode of biomass inhibition by methanethiol. We also found that the negative effect of methanethiol can be mitigated by lowering the salinity of the bioreactor medium. Furthermore, we developed a novel approach to measure the biological activity by sulfide measurements using UV-spectrophotometry. On the basis of this measurement method, it is possible to accurately estimate the unknown kinetic parameters in the mathematical model. PMID- 26154625 TI - Prognostic value of serial measurements of blood urea nitrogen in ambulatory patients with chronic heart failure. AB - BACKGROUND: Elevated blood urea nitrogen (BUN) in chronic heart failure (CHF) patients may represent increased neurohormonal activation. The purpose of this work was to evaluate the prognostic value of BUN and its variation in ambulatory patients with stable CHF. METHODS: In a retrospective analysis we included 241 outpatients with stable CHF (NYHA class I-III). We evaluated patients at baseline and at 6 months, then they have been followed for one year. The population was divided in four groups according to the median value of BUN at baseline and BUN change (percentage) at 6 months (group 1 BUN <25.2 mg/dL and variation <3.4%, group 2 BUN <25.2 mg/dL and >=3.4 %, group 3 BUN >=25.2 mg/dL and <3.4%, group 4 BUN >=25.2 mg/dL and >=3.4%). During a median follow-up of one year, 3 (1.3%) patients died and 49 (20.3%) were hospitalized due to worsening heart failure HF. RESULTS: The Kaplan-Meier curve showed that group 3 and group 4 had worse prognosis compared with group 1 and 2 and that a greater change in BUN, was associated with a further worsening of the prognosis (group 4). Multivariable models confirmed that cardiovascular mortality and HF hospitalizations were more frequent in patients who had an increase of BUN (HR 1.011 [IC 95% 1.002-1.021]; P=0.015). CONCLUSIONS: In ambulatory patients with stable chronic heart failure the increment of BUN is associated with increased cardiovascular mortality and heart failure hospitalizations at one-year. PMID- 26154626 TI - Measuring the Caregiver Burden of Caring for Community-Residing People with Alzheimer's Disease. AB - OBJECTIVES: To assess the direct and indirect effects of patient or caregiver factors on caregiver burden of caring for community-residing people with mild Alzheimer's disease (AD). METHODS: We conducted a cross-sectional study of patients diagnosed with AD from two hospitals and three communities in Taiyuan, China and their caregivers. For this survey, 200 patients with mild AD and their caregivers were selected. Caregivers were asked to provide sociodemographic information including age, gender, relationship with the patient, level of education, and number of contact hours per week with the patient. Caregiver burden was assessed using the Caregivers Burden Inventory. The caregivers also completed other measures including the Positive Aspects of Caregiving, the Family Adaptation, Partnership, Growth, Affection, and Resolve, and the Social Support Rating Scale. The patients with AD completed the Montreal Cognitive Assessment; their caregivers completed the Activities of Daily Living Scale and a questionnaire about the patients' Behavioral and Psychological symptoms of Dementia. The main outcome in this study was caregiver burden. The care receivers' level of cognitive function, physical function, and behavioral problems were treated as original stress; the primary appraisal variable was measured as the number of hours of caregiving in the previous week reported by the caregiver. Mediator variables included perceived social support, family function, and caregiving experience. Path analysis was used to build the interrelationship among caregiver burden and patient or caregiver factors. RESULTS: A lower level of cognitive function in patients (r = -0.28, p<0.001) and longer hours of caregiving (r = 0.17, p = 0.019) were related to increased caregiver burden. Greater social support (r = -0.23, p<0.001), family function (r = -0.17, p = 0.015) and caregiving experience (r = -0.16, p = 0.012) were related to decreased caregiver burden. Social support (r = 0.16, p = 0.040) and family function (r = 0.25, p = 0.002) were directly related to patients' level of cognitive functioning, but were mediator factors between level of cognitive function in patients and caregiver burden. Similarly, social support was a mediator factor between patients' daily function (r = -0.23, p = 0.004) and caregiver burden; while caregiving experience mediated the link between behavioral and psychological symptoms in patients (r = 0.36, p<0.001) and caregiver burden. CONCLUSION: Level of cognitive function and hours of caregiving were directly related to caregiver's burden. Social support, family function and caregiving experience could mediate the relationship between patient factors and caregiver burden. Focusing on patient factors and promoting caregiver care will be helpful in lowering the perceived burden of caregiving. PMID- 26154627 TI - Comparison of intraoral and extraoral approaches to mandibular angle fracture repair with cost implications. AB - OBJECTIVES/HYPOTHESIS: The objective of this study was to analyze outcomes of intraoral and extraoral approaches to mandibular angle fractures and provide cost estimates for comparison. STUDY DESIGN: A retrospective review from January 2005 to June 2013 was performed of patients who underwent open reduction internal fixation of mandibular angle fractures at a level I trauma center. METHODS: Patients were treated by three surgical specialties: otolaryngology-head and neck surgery, oral and maxillofacial surgery, and plastic and reconstructive surgery. Inpatient and outpatient medical records were reviewed for pertinent data including age, gender, duration of follow-up, presence of other mandible fractures, surgical approach, surgical team, operative time, and postoperative complications. RESULTS: Of the 155 patients with mandibular angle fractures, 74% underwent open reduction internal fixation through an intraoral approach, whereas 26% of patients were treated with an extraoral approach. The occurrence of any complication was 69.6% in the extraoral group and 39% in the intraoral group (P = 0.009). In propensity-weighted analysis, however, the occurrence of any complication was less frequent in intraoral cases but no longer statistically significant (odd ratio 0.28; 95% confidence interval, 0.08 to 1.02; P = 0.053). Operating room time was significantly shorter with the intraoral approach. We estimate that the intraoral approach directly saves at least $2,900 per case. CONCLUSION: We recommend the use of an intraoral approach for the repair of mandibular angle fractures when clinically appropriate. This can result in a comparable rate of success, however, with significant cost savings to the health care system. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:591-595, 2016. PMID- 26154628 TI - Tell Me Everything You Discussed: Children's Memory for Dyadic Conversations after a 1-Week or a 3-Week Delay. AB - In child abuse investigations, children are often asked to recount previous conversations related to the allegations (i.e., "conversational testimony"). To explore children's ability to provide conversational testimony, we staged a semi structured novel dyadic conversation between an adult researcher and 8-year-old children (n = 90). Children's gist recall and recognition memory for their own statements, their conversational partner's statements, and question-answer pairs were tested after either a 1-week or a 3-week delay. The results revealed that children recounted a minority of the conversation, although children recalled more after a short delay (7%) than after a long delay (4%). A majority of children's free recall statements were accurate (68%); however, approximately one third of their free recall statements were incorrect. Children almost exclusively recounted their own statements, and rarely recalled any of the adult's statements or the question-answer pairs during free recall. Reports of the adult's statements and question-answer pairs increased with cued recall questioning, but remained minimal. During recognition testing, children were able to distinguish between true and false recognition items for their own statements and the adult's statements, but performed at chance level on recognition items concerning question-answer pairs. Forensic implications of the results are discussed. PMID- 26154629 TI - The Paraoxonase 1 Gene c.-108C>T SNP in the Promoter Is Associated with Risk for Glioma in Mexican Patients, but Not the p.L55M or p.Q192R Polymorphisms in the Coding Region. AB - AIM: To evaluate the association of the paraoxonase 1 (PON1) gene polymorphisms c.-108C>T, p.L55M, and p.Q192R with the risk of glioma in Southeast Mexico. Decreased PON1 activity caused by polymorphisms has been observed in gliomas, thus supporting the theory that PON1 is involved in tumorigenesis in the brain. METHODS: Sixty-seven glioma patients and 58 control individuals were included. Three PON1 polymorphisms were genotyped by real-time PCR allelic discrimination using TaqMan probes: c.-108C>T in the promoter region, p.Q192R and p.L55M, both of which were in the coding region. Allele, genotype, and haplotype frequencies were assessed in cases and controls to test for statistical associations (STATA 10.2 package). RESULTS: Significant differences were found for the PON1 c.-108C>T polymorphism between the cases and controls. Compared to the controls the cases were more likely to be CT heterozygous (p = 0.002) or TT homozygous (p = 0.036); similarly cases were more likely to possess a T allele (p = 0.032). In contrast, the p.L55M and p.Q192R polymorphisms did not show significant differences between the glioma cases and controls (p > 0.05). CONCLUSION: The PON1 c.-108C>T polymorphism in the promoter region is associated with genetic risk for glioma. Conversely, p.L55M and p.Q192R polymorphisms in the coding region do not seem to have an influence in this population. PMID- 26154631 TI - Muscle histopathology in children with spastic cerebral palsy receiving botulinum toxin type A. AB - INTRODUCTION: Botulinum toxin A (BoNTA) is routine treatment for hypertonicity in children with cerebral palsy (CP). METHODS: This single-blind, prospective, cross sectional study of 10 participants (mean age 11 years 7 months) was done to determine the relationship between muscle histopathology and BoNTA in treated medial gastrocnemius muscle of children with CP. Open muscle biopsies were taken from medial gastrocnemius muscle and vastus lateralis (control) during orthopedic surgery. RESULTS: Neurogenic atrophy in the medial gastrocnemius was seen in 6 participants between 4 months and 3 years post-BoNTA. Type 1 fiber loss with type 2 fiber predominance was significantly related to the number of BoNTA injections (r = 0.89, P < 0.001). CONCLUSIONS: The impact of these changes in muscle morphology on muscle function in CP is not clear. It is important to consider rotating muscle selection or injection sites within the muscle or allowing longer time between injections. PMID- 26154632 TI - Brazilian Journal of Nephrology: looking ahead. PMID- 26154633 TI - Induction treatment in renal transplantation. PMID- 26154634 TI - Reliability of the Brazilian version of the PedsQL - ESDR questionnaire to evaluate quality of life of children and adolescents. AB - OBJECTIVE: To evaluate the reliability of the translation and cultural adaptation of the Pediatric Quality of Life Inventory (PedsQLTM) - End Stage Renal Disease (ESRD) - version 3.0 - children/adolescents and parents reports in Brazilian children with ESRD. METHODS: A group of 24 children and adolescents with ESRD, followed at Unidade de Nefrologia Pediatrica do Instituto da Crianca - HCFMUSP and 32 primary caregivers were interviewed according to the me methodology proposed by the creator of the original questionnaire. RESULTS: Statistical analysis using Cronbach's alpha resulted in values between 0.39 and 0.89 for all domains in initial statistical analysis. The domains that presented values lower than 0.5 were recalculated by age group, resulting in higher Cronbach's alpha values demonstrating the influence of the age in the perception of quality of life in ESRD patients. The overall rating of Cronbach's alpha values resulted in values of 0.81 and 0.71 in patients and PC reports, respectively, demonstrating good internal consistency. CONCLUSIONS: Ours results show that the Brazilian version of the questionnaires is valid, reliable and useful for measure HRQoL of children and adolescents ESRD, according to patients and PC reports. PMID- 26154635 TI - Clinical and epidemiological prevalence of glomerulopathies elderly in the city of Uberaba - MG. AB - INTRODUCTION: Currently, the elderly population of Brazil is suffering significant increase. Aging is a physiological process that causes changes in various organs, including the kidney. A kidney biopsy is of paramount importance to clarify the morphological changes of these entities. OBJECTIVES: The aim of this work was to conduct a clinical epidemiological analysis of elderly patients and evaluate the prevalence of major glomerulopathies that affect. METHODS: This is a retrospective and descriptive, with a review of 104 reports of renal biopsies of elderly aged over 60 years, performed in the Nefropatologia Federal University of Triangulo Mineiro (UFTM), between periods January 1996 and December 2010. Patients were grouped according to clinical syndrome. RESULTS: We reviewed 104 biopsies of elderly patients. Of these, 52.94% were male. The Hypertension was found in 50.54% of patients. The clinical syndrome was the predominant nephrotic syndrome (42.17%). Most disease was glomerular origin. The glomerulopathy was the most prevalent (34.07%). DISCUSSION/CONCLUSION: Through this review, we noted that the nephrotic syndrome was the main clinical syndrome and Podocytophaties glomerulopathies were more prevalent in the group of elderly patients undergoing renal biopsy. The analysis of renal biopsies of elderly patients is of paramount importance, since knowledge of the clinical manifestations of major glomerulopathies that affect this group, to assist in establishing the diagnosis and therapeutic management. PMID- 26154636 TI - Association between serum ferritin and lipid peroxidation in hemodialysis patients. AB - INTRODUCTION: Iron supplementation is one of the recommendations found in patients with chronic kidney disease (CKD), however, an overload of this mineral can contribute to oxidative stress, a condition closely related to the cardiovascular risk in these patients, as well as disease progression. OBJECTIVE: The objective of this study was to investigate whether ferritin levels are associated with oxidative stress marker MDA in patients on hemodialysis (HD). METHODS: Twenty HD patients (55.0 +/- 15.2 years, time of dialysis 76.5 +/- 46.3 months, BMI 23.6 +/- 3.0 kg/m2) were compared with 11 healthy subjects (50.9 +/- 8.0 years, BMI 23.8 +/- 1.9 kg/m2). Malondialdehyde (MDA) was measured by reaction with thiobarbituric acid and routine biochemical data were obtained from medical records. RESULTS: MDA levels were significantly higher in HD patients compared to the control group (13.2 +/- 5.3 nmol/mL vs. 5.1 +/- 2.7nmol/mL, p < 0.01). Twelve patients (60%) had ferritin values greater than the 500 ng/mL and there was a positive correlation between ferritin and MDA in HD (r = 0.66, p = 0.005, n = 17) patients. CONCLUSION: The excess iron stores in HD patients results in increased lipid peroxidation, and consequently contributes to increased oxidative stress in these patients. PMID- 26154637 TI - Prevalence of chronic kidney disease in newly diagnosed patients with Human immunodeficiency virus in Ilorin, Nigeria. AB - INTRODUCTION: Human immunodeficiency virus (HIV) the causative agent of Acquired immunodeficiency syndrome (AIDS) is an important cause of renal diseases in sub Saharan Africa. There is paucity of studies on the burden of chronic kidney disease (CKD) among patients with HIV/AIDS in the North-Central zone of Nigeria. METHODS: This is a cross-sectional study of 227 newly-diagnosed, antiretroviral naive patients with HIV/AIDS seen at the HIV clinic of the Medical Out-patient Department (MOPD) of University of Ilorin Teaching Hospital (UITH). They were matched with 108 control group. Laboratory investigations were performed for the participants. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and/or albumin creatinine ratio (ACR) > 30 mg/g. RESULTS: There were 100 (44%) males among the patients and 47 (43.5%) among the control group. The mean ages of the patients and controls were 40.3 +/- 10.3 years and 41.8 +/- 9.5 years respectively. CKD was observed in 108 (47.6%) among the patients and 18 (16.7%) of the controls (p = 0.01). The median CD4 T-cell count was significantly lower in patients with CKD. Ninety-three (41.0%) of the patients had dipstick proteinuria of > 2 +. The median albumin creatinine ratio (ACR) was significantly higher among the HIV-positive patients (272.3 mg/g) compared with the HIV negative controls (27.22 mg/g) p = 0.01. The CD4 T-cell count correlates positively with eGFR (r = 0.463, p = 0.001) and negatively with ACR (r = -0.806, p = 0.001). CONCLUSIONS: CKD is very common among patients with HIV/AIDS in Ilorin. Screening and early intervention for CKD should be part of the protocols in the management of these patients. PMID- 26154638 TI - Kidney function estimate among subjects aged 18-59 years in Tubarao, Santa Catarina: a population-based study. AB - INTRODUCTION: Among the increasing chronic degenerative diseases, chronic kidney disease (CKD) is a major public health challenge facing the 21st century. OBJECTIVES: To estimate the GFR by using the CKD-EPI formula among subjects aged 18-59 years, and to identify factors associated with glomerular filtration rate (GFR). METHODS: A cross-sectional population-based study was conducted on adults between November 2011 and March 2012. We collected sociodemographic, anthropometric, clinical, and laboratory tests to build a database. The Pearson's chi-square test was used to assess the association between variables, and the Student's t -test was used for mean comparison at 95% confidence level. RESULTS: A cohort of 371 adults was surveyed (63.8% women; 86.3% Whites). The mean age was 40.4 years (SD +/- 12.3). Of the total, 76.8% had normal GFR; 21.8% showed a slight decline, 1.1% a moderate decline, and 0.3% a significant decline in GFR. There were significant differences related to age and obesity, because the greater the age or the higher the body mass index, the lower the GFR of participants. Individuals with systemic hypertension showed a tendency towards a reduction in GFR compared to non-hypertensive population (p < 0.06). CONCLUSION: This study concluded that the vast majority of the surveyed subjects had normal GFR levels, and that only 1.4% (95% CI: 0.3 - 2.4) had moderate or severe dysfunction. PMID- 26154639 TI - Mortality in patients with chronic kidney disease undergoing hemodialysis in a public hospital of Peru. AB - INTRODUCTION: The Peruvian Ministry of Health does not have a national program of hemodialysis and hospitals that offer it have coverage problems, which may result in increased mortality. OBJECTIVE: We evaluated mortality of a population with incident hemodialysis in a Peruvian public hospital as well as its associated factors. METHODS: Retrospective and descriptive study of a population over 18 years-old who started treatment between January 1, 2012 and December 31, 2013 with the final follow-up day on31 March 2014. We used bivariate and multivariate logistic regression models to evaluate factors associated with mortality and Kaplan Meier curves were used to determine the probability of survival. RESULTS: We included 235 patients with a mean age of 56.4 +/- 15.8 years. Median follow-up was 0.6 years (IQR 0.3 to 1.5). 50% of years withdrew from therapy during the study for lack of financial resources or space available. The third month mortality was 37.7% (95% CI 4.7 to 48.5) and 49.5% (95% CI 5.8 to 61.4) at 7 months. There was a trend towards lower mortality when patients had more than 6 months with a diagnosis of chronic kidney disease (CKD) (OR = 0.39 [95% CI 0.12 to 1.27]) and when the patient was admitted with scheduled dialysis (OR = 0.28 [95% CI 0.01 to 2.28]). CONCLUSION: Half of patients died within seven months of follow-up. Scheduled dialysis and having longer time with CKD diagnosis tend to be associated with lower mortality. PMID- 26154640 TI - Early changes in serum albumin: impact on 2-year mortality in incident hemodialysis patients. AB - INTRODUCTION/OBJECTIVE: We evaluated the predictability of early changes in serum albumin (sAlb) on the two-year mortality of incident hemodialysis patients. METHODS: Observational, longitudinal retrospective study using the database of Fresenius Medical Care of Latin America. Adult patients starting dialysis from January/2000 to June/2004, from 25 centers were included. Changes in sAlb during the first 3 months on hemodialysis were used as the main predictor. The outcome was death from any cause. RESULTS: 1,679 incident patients were included. They were 52 +/- 15 years old, 58.7% male and 21.5% diabetic, with a median sAlb of 38 g/L (bromocresol green). 923 patients had sAlb < 38 g/L (Low sAlb Group) and 756 ones had sAlb > 38.0 g/L (Adequate sAlb Group). The mortality was significantly higher in Low sAlb Group (17% vs. 11%, p < 0.001). Early changes in sAlb significantly affected two-year mortality. Factoring the Kaplan Meier curve of Low sAlb Group by the presence of an increase in sAlb uncovered of a statistically significant difference in mortality favoring the ones whose sAlb went up (19% vs. 15%, p = 0.043). Differently, patients from Adequate sAlb Group with a decrease in their sAlb had a statistically higher mortality rate (13% vs. 8%, p = 0.029). CONCLUSIONS: Early sAlb changes showed a significant predictive power on mortality at 2 years in incident hemodialysis patients. Those with low initial sAlb may have a better prognosis if their sAlb rises. In contrast, patients with satisfactory initial levels can have a worsening of their prognosis in the case of an early reduction in sAlb. PMID- 26154641 TI - Different induction therapies for kidney transplantation with living donor. AB - INTRODUCTION: Indications for induction therapy is not consensual in living donors. OBJECTIVE: The objective of this study was compare no induction with thymoglobulin and basiliximab induction in the incidence of acute rejection in kidney transplantation with living donor. METHODS: We select all cases of renal transplantation with living donor performed in Hospital das Clinicas de Botucatu da UNESP during the period of January 2010 to December 2013. The group was divided by the type of medication used for induction. RESULTS: A total of 90 patients were evaluated. There were no differences in baseline characteristics of age and underlying disease. The rate of biopsy-proven acute rejection was higher in the group without induction (42.9%) compared to basiliximab group (20%) and Thymoglobulin (16.7%), p = 0.04. The rejection by compatibility shows that the identical had the lower rejection rate (10%). The haploidentical group without induction had the highest rejection rates (53.3%). In all distinct group the rejection rates were similar with basiliximab or Thymoglobulin, p = NS. The use of induction therapy was associated independently with a lower risk of rejection (OR = 0.32 CI: 0.11 to 0.93, p = 0.036). There were no differences in renal function at 6 months and patient survival and graft in the three groups. DISCUSSION: The haploidentical patients without induction were those with higher rates of acute rejection. The group of patients induced with Thymoglobulin had a higher immunological risk, however showed low rates of rejection. CONCLUSION: The use of induction therapy resulted in lower rates of rejection in transplantation with living donor. PMID- 26154642 TI - Long-term outcomes of elderly kidney transplant recipients. AB - INTRODUCTION: The number of elderly patients with chronic kidney disease increases progressively, challenging the allocation algorithms in a scenario of organ shortage for transplantation. OBJECTIVE: To evaluate the impact of age on patient and graft survival. METHODS: Evolution of all 366 patients greater than 60 years transplanted between 1998 and 2010 was analyzed versus a control group of 366 younger patients matched for gender, type of donor (living or deceased) and year of transplantation. RESULTS: Diabetes mellitus (HR 1.8; IC 1.2-2.6; p = 0,003) and prioritization (HR 2.9; IC 1.2-2.6; p < 0,001), but not age, were independent factors for kidney graft loss. CONCLUSION: Advanced age was not related to negative outcomes after kidney transplantation, after excluding recipient death as a cause of allograft loss. Higher mortality rate in this group was associated to a higher frequency of comorbidities, especially diabetes mellitus. PMID- 26154643 TI - Approach to thrombotic occlusion related to long-term catheters of hemodialysis patients: a narrative review. AB - Currently, permanent catheters (pCVC) are becoming an alternative vascular access for long-stay patients in whom arteriovenous access cannot be made. Occlusion is a commun mechanical complication related to pCVC, leading to inadequate dialysis dose and frequent changes of local catheter location, which can cause exclusion of vascular sites. The aim of this study was to perform a narrative review of treatment of pCVC thrombotic occlusion in HD patients. The treatment of CVCP thrombosis typically consists on the saline infusion or administration of thrombolytics such as tissue plasminogen activated, reteplase and urokinase. There are few studies on the use of alteplase in pCVC clogged in oncology area and in dialysis population, and they all report success with the use of thrombolytic therapy ranging from 80-95% of cases, using 1mg/ml. Due to the high cost of alteplase, studies have suggested that cryopreservation and fractionated alteplase dose have made its use financially viable. PMID- 26154644 TI - Use of Thymoglobulin(r) (antithymocyte immunoglobulin) in renal transplantation: practical guide. AB - The combination of immunosuppressive drugs is part of the treatment regimen of patients undergoing kidney transplantation (RT). Thymoglobulin(r), a rabbit immunoglobulin directed against human thymocytes, is the most commonly agent used for induction therapy in RT in the US. In Brazil, Thymoglobulin(r) is approved by ANVISA for the use in patients who underwent kidney transplantation and despite being widely used, there are controversies regarding the drug administration. We prepared a systematic review of the literature, evaluating studies that used Thymoglobulin(r) for induction and for acute rejection treatment in patients undergoing RT. The review used the computadorized databases of EMBASE, LILACS and MedLine. Data were extracted from the studies concerning general features, methodological characteristics and variables analyzed in each study. From the results, a practical guide was prepared analyzing various aspects on the use of Thymoglobulin(r) in patients submitted to RT. PMID- 26154645 TI - Why eating star fruit is prohibited for patients with chronic kidney disease? AB - New studies have shown the mechanism by which the star fruit (Averrhoa carambola) becomes toxic to individuals with chronic kidney disease (CKD). The aim of this study was to review the current literature on the topic. This is a review article, with publications from 2000 to 2014 available in scientific database. There are reports that neurotoxicity is due to the presence of oxalate in star fruit, but recent findings show that the neurotoxic effect of the toxin is by caramboxin, which appears to inhibit the GABAergic system which is the major inhibitory system in the central nervous system (CNS), involving changes as sobs and confusion, to more serious conditions such as seizures and death. It is important to multidisciplinary action to alert patients with CKD as the prohibition of the star fruit consumption. PMID- 26154646 TI - GSTM1 and GSTT1 genes null polymorphisms in kidney cancer susceptibility: evidence based on a meta-analysis. AB - INTRODUCTION: Renal cancer is a complex and multifactorial oncourologic disease. OBJECTIVE: To conduct a meta-analysis in order to investigate the association of GSTM1 and GSTT1 genes null polymorphisms in renal cancer. METHOD: Case-control studies in humans, published from 1999 to 2013, that investigated the association of GSTM1 and GSTT1 genes null polymorphisms in renal cancer were grouped in order to make of this meta-analysis. RESULTS: Ten articles were selected on the subject proposed. No associations were found between polymorphisms of GSTM1-null (OR = 1.015, 95% CI = 0.897 to 1.147) and GSTT1-null (OR = 1.081, 95% CI = 0.791 to 1.479) and renal cancer. CONCLUSIONS: Based on the results obtained, we conclude that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of developing renal cancer, since they have limited role, if there is any on effective contribution in the development of renal tumors. PMID- 26154647 TI - Inflammation and poor response to treatment with erythropoietin in chronic kidney disease. AB - The prevalence of kidney chronic disease (CKD) has increased in recent years and several risk factors have been associated with the onset and progression of CDK, such as obesity, hypertension and diabetes mellitus. In addition, anemia is one of the complications of CRD, mainly by iron and erythropoietin (EPO) deficiency and the management of this situation is with exogenous erythropoietin, but patients undergoing dialysis present chronic inflammatory process followed by EPO resistance and anemia, malnutrition, worse of atherosclerosis and increased mortality ratio. The aim of this study was to review the association of erythropoietin resistance and chronic inflammatory process in patients with chronic renal disease. PMID- 26154648 TI - [Gitelman's Syndrome: from diagnosis to follow-up during pregnancy]. AB - Gitelman's Syndrome (GS) is a rare autosomal recessive salt-wasting nephropathy, classically characterized by hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and low blood pressure. Fatigue, muscle weakness and muscle paralysis are common symptoms. Besides the typical electrolyte disturbances, others laboratory findings include hyperreninemia and secondary hyperaldosteronism. Bilateral nephrocalcinosis may occur. The treatment consists of potassium replacement and use of aldosterone antagonists. The best approach to pregnant women with GS is yet to be defined. However, we emphasize the need for ions supplementation, weight control as a clinical tool for assessing the water balance, and frequent monitoring of the fetus and amniotic fluid levels. The surgical risk associated with cesarean section in a patient with GS is not yet defined. Despite the risks related to symptomatic episodes of hypokalemia/hypomagnesemia, GS has a good prognosis when treated properly. Pregnancy imposes the need for more intensive control of the disease, but has a good prognosis for the mother and neonate. PMID- 26154649 TI - [Visceral leishmaniasis and pregnancy in renal transplanted patient: case report]. AB - Visceral leishmaniasis (VL) is a severe and potentially fatal disease caused by different Leishmania species, Leishmania chagasi prevailing in Brazil. Main symptoms include fever, malaise, anorexia, weight loss and abdominal enlargement with typically occurring hepatosplenomegaly Currently, VL is considered an opportunistic infection in immunocompromised hosts, including solid organ transplanted patients. The present study reports a case of VL associated to pregnancy after renal transplantation. PMID- 26154650 TI - Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia. AB - We observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure. PMID- 26154651 TI - [Case report: end stage renal disease in a chronic kidney patient on warfarin therapy]. AB - BACKGROUND: Warfarin therapy can provoke severe hematuria and acute kidney injury with the presence of occlusive red blood cell casts. These findings are compatible with a recently described disease entity, warfarin related nephropathy, which adversely affects renal and patient outcome. CASE REPORT: We report a 74-year-old man with chronic kidney disease stage 3 A, who developed a decline in glomerular filtration rate (GFR) after the initiation of warfarin therapy due to of atrial fibrillation. The diagnosis could be confirmed by renal histology which showed occlusion of renal tubules by red blood cells and casts consistent with this diagnosis. The patient did not recover the GFR and started renal replacement therapy in June (fourteen months after starting warfarin) 2014. DISCUSSION: The aim of the present report is to alert for this drug recognized complication and reinforce the need of carefully motorization of kidney function and coagulation parameters in patients treated with warfarin. The pathogenesis and outcome of warfarin-related nephropathy is also discussed here. PMID- 26154652 TI - [Renal transplantation without maintenance immunosuppression. Identical twins and kidney transplantation following a successful bone marrow graft]. AB - Renal transplantation without maintenance immunosuppression has been sporadically reported in the literature. The cases include non-adherent patients who discontinued their immunosuppressive medications, transplantation between identical twins, kidney transplantation after a successful bone marrow graft from the same donor and simultaneous bone marrow and kidney transplantation for the treatment of multiple myeloma with associated renal failure. There are also ongoing clinical trials designed to induce donor specific transplant tolerance with infusion of hematopoietic cells from the same kidney donor. Here we describe two cases of renal transplantation without immunosuppression as examples of situations described above. PMID- 26154653 TI - Effect of adjustable gastric banding on quality of life and weight loss in the Helping Evaluate Reduction in Obesity (HERO) registry study: 2 year analysis. AB - OBJECTIVE: This report from the Helping Evaluate Reduction in Obesity (HERO) Study investigated weight loss, health-related quality of life (HRQOL), and factors predictive of HRQOL improvement during a 2 year period following Lap-Band AP implantation (post-LBAP). RESEARCH DESIGN AND METHODS: This prospective, observational study included patients with 1 and 2 year follow-up data post-LBAP (N = 585). Changes in body mass index (BMI), percentage of weight loss (%WL), excess weight loss (%EWL) and HRQOL (Impact of Weight on Quality of Life [IWQOL] Lite measure), and differences between <30% EWL and >=30% EWL subgroups were assessed at 1 and 2 years post-LBAP. Multiple linear regression examined association of %EWL groups with IWQOL-Lite scores controlling for age, gender, region (US vs outside US), household income, employment status, and comorbidities. RESULTS: Most patients were female (80.2%) and from the US (64.8%); overall mean (SD) age was 43.6 (11.28) years and 65.8% of patients had >=30% EWL at year 2. At 2 years post-LBAP, mean %EWL was 43.5%; %EWL was 12.4% in the <30% EWL group and 59.6% in >=30% EWL group (P <= 0.0001). Changes in IWQOL total and subscores were significantly greater in >=30% EWL versus <30% EWL patients (all P < 0.0005) at years 1 and 2; Self-Esteem and Physical subscores had the largest changes. Multiple regression analysis showed that patients with >=30% EWL had clinically meaningful improvements in HRQOL compared with patients having <30% EWL (P <= 0.001). Similarly, US patients and females had a clinically significant change in IWQOL score versus their counterparts (P <= 0.001). Conversely, income, comorbidities and employment status were not significant predictors of change in IWQOL scores at year 2. CONCLUSIONS: These results support and extend findings regarding the effectiveness of LBAP for weight loss and illustrate the importance of >=30% EWL as a significant factor in predicting clinically significant improvement in HRQOL 1 and 2 years post-LBAP. CLINICAL TRIAL REGISTRATION: NCT00953173. PMID- 26154654 TI - Parental social consequences of having a child with cerebral palsy in Denmark. AB - AIM: To analyse the social situation of parents who have a child with cerebral palsy (CP). METHOD: This was a population-based longitudinal study with linkage to public registries. Parents of children with CP (n=3671) identified in the Danish CP Registry were compared with 17,983 parents of children without CP. Employment, income, cohabitation status, and presence of additional children were factors analysed during a follow-up period of 28 years. We followed parents from before their child was born and up to the age of 43 years of the child. RESULTS: Mothers of children with CP under the age of 10 were less often employed: odds ratio [OR] of employment at age 5y 0.45 (95% confidence interval [CI] 0.36-0.57), but only 11% left the labour market. Mothers of children without CP had higher incomes: ratio full-time working 1.11 (95% CI 1.07-1.15). The risk of not living together was not increased among parents of children with CP: at age 5 years OR 1.04 (95% CI 0.84-1.28). Parents of children with CP as the first born postponed or more seldom had subsequent children: hazard ratio [HR] 0.75 (95% CI 0.68 0.83). INTERPRETATION: The Danish welfare system seems to have succeeded in keeping parents in the labour market and living together with their child. Special attention needs to be paid to the financial situation of families with children with CP under 10 years of age. PMID- 26154655 TI - Three-Dimensional Conductive Gel Network as an Effective Binder for High Performance Si Electrodes in Lithium-Ion Batteries. AB - Silicon (Si) has been widely investigated as a candidate for lithium-ion batteries (LIBs) due to its extremely high specific capacity. The binders play a key role in fabricating high-performance Si electrodes which usually suffer from the huge volume expansion associated with the alloying and dealloying processes. Here we develop a facile route to prepare a three-dimensional (3D) conductive interpenetrated gel network as a novel binder for high-performance Si anodes through chemically cross-linking of acrylic acid monomer followed by the in situ polymerization of aniline. The excellent electrical conductivity, strong mechanical adhesion and high electrolyte uptake render the conductive gel network a potential binder for high-performance Si anodes. The resultant Si anodes exhibit excellent cycling stability, high Coulombic efficiency and superior rate capability, revealing better electrochemical properties compared to the Si anodes with conventional binders. The 3D conductive gel binder could not only accommodate the volume expansion and maintain electric connectivity, but also assist in the formation of stable solid electrolyte interphase (SEI) films. Such a strategy sheds light on the design of polymer binders in LIBs, especially for high-capacity electrode materials with huge volume changes during long-term cycling. PMID- 26154656 TI - Increased Long-Term Mortality among Black CABG Patients Receiving Preoperative Inotropic Agents. AB - The aim of this study was to examine racial differences in long-term mortality after coronary artery bypass grafting (CABG), stratified by preoperative use of inotropic agents. Black and white patients who required preoperative inotropic support prior to undergoing CABG procedures between 1992 and 2011 were compared. Mortality probabilities were computed using the Kaplan-Meier product-limit method. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 15,765 patients underwent CABG, of whom 211 received preoperative inotropic agents within 48 hours of surgery. Long-term mortality differed by race (black versus white) among preoperative inotropic category (inotropes: adjusted HR = 1.6, 95% CI = 1.009-2.4; no inotropes: adjusted HR = 1.15, 95% CI = 1.08-1.2; P(interaction) < 0.0001). Our study identified an independent preoperative risk-factor for long-term mortality among blacks receiving CABG. This outcome provides information that may be useful for surgeons, primary care providers, and their patients. PMID- 26154657 TI - Effects of Acute Ingestion of Native Banana Starch on Glycemic Response Evaluated by Continuous Glucose Monitoring in Obese and Lean Subjects. AB - An abnormal glycemic profile, including postprandial glycemia and acute glucose spikes, precedes the onset of overt diabetes in obese subjects. Previous studies have shown the beneficial effects of chronic native banana starch (NBS) supplementation. In this study, we examined the effects of acute ingestion of NBS on glycemic profiles by means of continuous glucose monitoring in obese and lean subjects. In a crossover study, obese and lean subjects consumed beverages containing either 38.3 g of NBS or 38.3 g of digestible corn starch (DCS) twice daily during 4 days. On day 5, a 3-h meal tolerance test (MTT) was performed to evaluate glucose and insulin responses. After 1 week of washout period, treatments were inverted. NBS supplementation reduced the 48-h glycemia AUC in lean, obese, and in the combined group of lean and obese subjects in comparison with DCS. Postprandial glucose and insulin responses at MTT were reduced after NBS in comparison with DCS in all groups. However, no changes were observed in glycemic variability (GV) indexes between groups. In conclusion, acute NBS supplementation improved postprandial glucose and insulin responses in obese and lean subjects during 48 h of everyday life and at MTT. Further research to elucidate the mechanism behind these changes is required. PMID- 26154658 TI - The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells. AB - The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR). TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR) expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models. PMID- 26154660 TI - Environmental Resource Management in Borderlands: Evolution from Competing Interests to Common Aversions. AB - Great enthusiasm is attached to the emergence of cross-border regions (CBRs) as a new institutional arrangement for dealing with local cross-border environmental resource management and other issues that remain too distant from national capitals and/or too expensive to be addressed in the traditional topocratic manner requiring instead local adhocratic methods. This study briefly discusses the perceived value of CBRs and necessary and sufficient conditions for the successful and sustainable development of such places. Then, assuming that necessary conditions can be met, the study investigates an intriguing hypothesis concerning the catalyzing of sustainable consensus for cross-border resource management based on a game theoretical approach that employs the use of dilemma of common aversion rather than the more traditional dilemma of competing common interests. Using this lens to investigate a series of events on the Pacific northwestern Canadian-American border in a part of the Fraser Lowland, we look for evidence of the emergence of an active and sustainable CBR to address local trans-border resource management issues. Although our micro-level scale fails to conclusively demonstrate such evidence, it does demonstrate the value of using this approach and suggests a number of avenues for further research. PMID- 26154661 TI - A Game of Hide and Seek: Expectations of Clumpy Resources Influence Hiding and Searching Patterns. AB - Resources are often distributed in clumps or patches in space, unless an agent is trying to protect them from discovery and theft using a dispersed distribution. We uncover human expectations of such spatial resource patterns in collaborative and competitive settings via a sequential multi-person game in which participants hid resources for the next participant to seek. When collaborating, resources were mostly hidden in clumpy distributions, but when competing, resources were hidden in more dispersed (random or hyperdispersed) patterns to increase the searching difficulty for the other player. More dispersed resource distributions came at the cost of higher overall hiding (as well as searching) times, decreased payoffs, and an increased difficulty when the hider had to recall earlier hiding locations at the end of the experiment. Participants' search strategies were also affected by their underlying expectations, using a win-stay lose-shift strategy appropriate for clumpy resources when searching for collaboratively-hidden items, but moving equally far after finding or not finding an item in competitive settings, as appropriate for dispersed resources. Thus participants showed expectations for clumpy versus dispersed spatial resources that matched the distributions commonly found in collaborative versus competitive foraging settings. PMID- 26154662 TI - Neonatal Herpes Simplex Virus Infection. AB - Herpes simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement. PMID- 26154659 TI - Manganese-Induced Parkinsonism and Parkinson's Disease: Shared and Distinguishable Features. AB - Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson's disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson's disease (PD). PMID- 26154663 TI - New Horizons for Pediatric Antibiotic Stewardship. AB - Antibiotic resistance remains a major health threat and the overuse of antimicrobials contributes to this serious problem. Antimicrobial stewardship programs (ASPs) are effective in decreasing the inappropriate use of antimicrobials. The development of pediatric ASPs is increasing and these programs have proven effective in optimizing antimicrobial use in children. The value of ASPs is gaining recognition and the expansion of stewardship into additional health care settings is expected. Collaborative efforts are underway among pediatric ASPs to enhance best practices and develop efficient and effective strategies to minimize unnecessary antimicrobial use in children. PMID- 26154666 TI - Rethinking Workarounds. PMID- 26154664 TI - Strain Variation and Disease Severity in Congenital Cytomegalovirus Infection: In Search of a Viral Marker. AB - The wide spectrum of congenital cytomegalovirus (CMV) disease and known differences in the biology and in vitro growth of CMV strains continue to drive studies in search for specific viral genetic determinants that may predict severity of congenital CMV disease. Several CMV genes have been studied in detail in congenitally infected children, but the complexity of the viral genome and differences in the definition of symptomatic disease versus asymptomatic CMV infection continue to raise questions related to what constitutes a pathogenic CMV strain. PMID- 26154667 TI - The Rise and Stall of eLearning: Best Practices for Technology-Supported Education. AB - eLearning is a commonly used term in education today, but what does it mean? This article explores issues that nurse planners and administrators need to be aware of in planning how technology-based education is most effectively delivered. PMID- 26154665 TI - The Complexities of the Diagnosis and Management of Kawasaki Disease. AB - Kawasaki disease (KD) must be considered in the differential diagnosis of any child with fever for 4 to 5 days and compatible clinical and laboratory features, and in any infant with prolonged fever and compatible laboratory features, even in the absence of the classic clinical signs. Prompt therapy is required, because delayed or unrecognized KD can lead to lifelong heart disease or death in previously healthy children. Most children with KD respond to a single 2 g/kg dose of intravenous gammaglobulin with oral aspirin, but a small subset require additional therapies to resolve the clinical illness. PMID- 26154668 TI - Implementing a Pain Care Toolkit to Improve Patient Perception of Pain Care. AB - As a result of the Hospital Value-Based Purchasing (VBP) Program, hospitals are now faced with reimbursement for quality of care, including patient perception of care, as measured by the Hospital Compare Assessment of Health Plans Survey, which includes the patient experience with pain care. Through the implementation of a Pain Care Quality Toolkit, patient perception of pain care can be improved, thus increasing the possibility of maximum reimbursement through the VBP. PMID- 26154669 TI - Patient-Centered Leadership. AB - Patient-centered care has garnered new attention, as it is linked to health system reimbursement. The background for patient-centered care has evolved from a rich history of evidence, indicating that the patient experience matters. This article addresses the history of patient-centered care and the evidence supporting patient-centered leadership. PMID- 26154670 TI - Incorporating Rapid Cycle Deliberate Practice Into Nursing Staff Continuing Professional Development. AB - Rapid Cycle Deliberate Practice (RCDP) is an innovative concept used to teach a sequence of predetermined skills to learners in a short period of time. When implemented correctly, learners build on their actions (deliberate practice) repeatedly, over a short period of time (rapid cycle). Incorporating RCDP into a nursing mandatory education program has improved both the satisfaction of the staff attending a mandatory education day and improved their response to patients in cardiac arrest. PMID- 26154671 TI - Preceptor and Self-Evaluation Competencies Among New RN Graduates. AB - Four transition-to-practice programs for new RN graduates who had not yet found employment in nursing were based on the Quality and Safety Education for Nurses (QSEN) competencies of knowledge, skills, and attitudes (KSAs). To support consistent evaluation of participants by preceptors, a 35-item tool was developed that used a 4-point scale to assess selected behaviors. This article describes the initial reliability and validity testing of the tool, which had good internal consistency, with a Cronbach's alpha of 0.92 for preceptor evaluation of participants and 0.82 when used as a self-evaluation tool. Six content experts evaluated the tool's face validity; it successfully discriminated between junior level baccalaureate nursing students and nursing faculty. Although the tool does not exhaustively reflect the QSEN KSAs, it provides a way to assess competencies among new nurse graduates. PMID- 26154673 TI - Enhancing Trifocal Leadership Practices Using Simulation in a Pediatric Charge Nurse Orientation Program. AB - A well-established charge nurse orientation program was enhanced with the addition of a simulation, addressing three primary populations (the trifocus) with whom charge nurses interact: patients, patients' parents, and other staff members. In this pilot quality improvement project, 20 staff nurses enrolled in the orientation program and were assigned a mentor. Only one participant used the mentorship opportunity; therefore, it is not discussed here. Twelve nurses completed all charge nurse classes and a simulation scenario of caring for a deteriorating infant. The nurses were given an opportunity to reflect on leadership practices after the simulation. Thematic analysis from qualitative, reflective data supported the enhanced understanding of managing complex patients, a code situation, and teams; guiding a team's novice nurse; leading as a charge nurse; and using clinical and critical thinking skills. All nurses reported that the simulation as experiential learning helped them to meet their leadership goals. PMID- 26154674 TI - Defining a Role for Nursing Education in Staff Nurse Participation in Antimicrobial Stewardship. AB - The role of the staff nurse in antimicrobial stewardship programs (ASPs) is not clearly defined. This study explored the ASP educational needs of staff nurses, using survey, focus group, and Delphi methods of engaging nurse educators. Low awareness of components of ASPs and areas of educational need were identified. PMID- 26154675 TI - Advanced Practice Nursing Simulation for Neonatal Skill Competency: A Pilot Study for Successful Continuing Education. AB - BACKGROUND: Skill readiness remains a challenge for all health care professionals who are involved in direct patient care. Researchers suggest that skill retention may decrease within 6 months of an educational session. The purpose of this study was to explore competency retention for high-risk, low-frequency procedures, specifically, managing a difficult airway and placing a laryngeal mask airway, using a web-based content refresher. METHOD: The pilot study was conducted in two sessions. Session one established clinical skill competency. Six months later, the advanced practice RNs were randomized into two groups. Group 1 reviewed didactic content and participated in a complex airway management simulation. Group 2 participated only in a complex airway management simulation. RESULTS: This study showed a positive trend in maintaining competency for a low-frequency procedure for which complex airway management was given, using web-based content review. It is feasible to maintain competency for low-frequency procedures using web-based content refreshers. CONCLUSION: This pilot study benefited advanced practice nurses by providing them with the potential to maintain competency in this high-risk, low-frequency procedure. Continuing education is an important consideration for health care organizations. PMID- 26154676 TI - Intuitive Decision Making as the Culmination of Continuing Education: A Theoretical Framework. AB - The ability to make sound clinical decisions is the cornerstone of excellent nursing care and the goal of continuing nurse educators. Research has revealed that expert nurses make fewer errors in decision making; it also has shown differences in the decision-making process of expert nurses, compared with novice nurses. Specifically, expert nurses report a greater use of intuitive decision making. Accordingly, an important goal for continuing nurse educators is the development of intuitive decision making by nurses. This article proposes a pattern-based, constructivist educational framework that synthesizes Benner's novice to expert (NTE) theory, Damascio's somatic marker hypothesis (SMH), and Hammond's cognitive continuum theory (CCT). This framework provides a foundation for continuing education that fosters the development of intuitive decision making in nurses. Although this framework needs further empirical validation, it is theoretically sound and applicable to all areas of nursing, and its implementation could help reduce errors in decision making by nurses, thus improving patient outcomes. PMID- 26154677 TI - Computed Tomography Contrast Enhancement Following Renal Cryoablation--Does it Represent Treatment Failure? AB - OBJECTIVE: For minimal invasive treatment of small renal masses, cryoablation has gained popularity. Treatment success is defined as the absence of contrast enhancement on postoperative imaging of the cryoablated lesion, but contrast enhancement does not necessarily equal treatment failure. This present study investigates the proportion of spontaneous resolutions after initial contrast enhancement in relation to cryoablation. MATERIALS AND METHODS: Data were collected from a prospectively maintained clinical database containing all patients treated with primary laparoscopic and percutaneous cryoablation between August 2005 and December 2013. All images were evaluated with regard to preoperative aspects and dimensions used for an anatomical classification (PADUA) score, cryolesion size, contrast enhancement pattern, and tissue density. RESULTS: A total of 107 patients with a biopsy-verified malignant tumor were included in the study. On postoperative imaging, 33 (31%) patients presented with contrast enhancement. Spontaneous resolution was observed in 15 (45%) patients after a mean follow-up time of 14 months. Patients with cryolesions that resolved spontaneously were found to have a less anatomical complex tumor compared to patients with treatment failure (PADUA 7.8 vs 9.5, p < 0.01). A total of seven patients with a PADUA score >=10 and contrast-enhancing cryolesions were found to have treatment failure. No association was found among body mass index, histology, treatment modality, enhancement pattern, number of applied cryoprobes, and resolution. CONCLUSION: Postoperative contrast enhancement is commonly observed after cryoablation and a large portion of these lesions often resolves spontaneously, thus not representing treatment failure. In patients with a high preoperative PADUA score and postoperative contrast enhancement of the cryolesion, treatment failure or recurrent disease should be suspected. PMID- 26154678 TI - [Histological diagnostics of enucleated eyes]. AB - Enucleated eyeglobes represent a challenge for the pathologist, as their appraisal requires specific ophthalmological knowledge. Part 1 of this CME article dealt with macroscopic findings in eyeglobes, in order to facilitate adequate cutting planes to retrieve pathologies histologically. Part 2 which is presented here teaches basic histology of eye-specific tissues (e.g., cornea, anterior chamber angle, retina, and optic nerve). Theses structures show typical changes in blinded eyes. Knowledge of these changes, together with awareness of fundamental ophthalmic disease entities and surgical strategies (see part 1), will many times allow to deduce the pathophysiology that finally culminated in blindness and enucleation. Disease entities more closely discussed in this article include corneal ulcers, rubeotic secondary glaucomas, and chronic degenerative retinal diseases. PMID- 26154680 TI - Synthesis and Characterization of Atomically Flat Methyl-Terminated Ge(111) Surfaces. AB - Atomically flat, terraced H-Ge(111) was prepared by annealing in H2(g) at 850 degrees C. The formation of monohydride Ge-H bonds oriented normal to the surface was indicated by angle-dependent Fourier-transform infrared (FTIR) spectroscopy. Subsequent reaction in CCl3Br(l) formed Br-terminated Ge(111), as shown by the disappearance of the Ge-H absorption in the FTIR spectra concomitant with the appearance of Br photoelectron peaks in X-ray photoelectron (XP) spectra. The Br Ge(111) surface was methylated by reaction with (CH3)2Mg. These surfaces exhibited a peak at 568 cm(-1) in the high-resolution electron energy loss spectrum, consistent with the formation of a Ge-C bond. The absorption peaks in the FTIR spectra assigned to methyl "umbrella" and rocking modes were dependent on the angle of the incident light, indicating that the methyl groups were bonded directly atop surface Ge atoms. Atomic-force micrographs of CH3-Ge(111) surfaces indicated that the surface remained atomically flat after methylation. Electrochemical scanning-tunneling microscopy showed well-ordered methyl groups that covered nearly all of the surface. Low-energy electron diffraction images showed sharp, bright diffraction spots with a 3-fold symmetry, indicating a high degree of order with no evidence of surface reconstruction. A C 1s peak at 284.1 eV was observed in the XP spectra, consistent with the formation of a C-Ge bond. Annealing in ultrahigh vacuum revealed a thermal stability limit of ~400 degrees C of the surficial CH3-Ge(111) groups. CH3-Ge(111) surfaces showed significantly greater resistance to oxidation in air than H-Ge(111) surfaces. PMID- 26154679 TI - Systematic Analysis of the Genetic Variability That Impacts SUMO Conjugation and Their Involvement in Human Diseases. AB - Protein function has been observed to rely on select essential sites instead of requiring all sites to be indispensable. Small ubiquitin-related modifier (SUMO) conjugation or sumoylation, which is a highly dynamic reversible process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified, has shown to be especially valuable in cellular biology. Motivated by the significance of SUMO conjugation in biological processes, we report here on the first exploratory assessment whether sumoylation related genetic variability impacts protein functions as well as the occurrence of diseases related to SUMO. Here, we defined the SUMOAMVR as sumoylation related amino acid variations that affect sumoylation sites or enzymes involved in the process of connectivity, and categorized four types of potential SUMOAMVRs. We detected that 17.13% of amino acid variations are potential SUMOAMVRs and 4.83% of disease mutations could lead to SUMOAMVR with our system. More interestingly, the statistical analysis demonstrates that the amino acid variations that directly create new potential lysine sumoylation sites are more likely to cause diseases. It can be anticipated that our method can provide more instructive guidance to identify the mechanisms of genetic diseases. PMID- 26154682 TI - Growing Older. PMID- 26154681 TI - Small-signal modulation characteristics of a polariton laser. AB - Use of large bandgap materials together with electrical injection makes the polariton laser an attractive low-power coherent light source for medical and biomedical applications or short distance plastic fiber communication at short wavelengths (violet and ultra-violet), where a conventional laser is difficult to realize. The dynamic properties of a polariton laser have not been investigated experimentally. We have measured, for the first time, the small signal modulation characteristics of a GaN-based electrically pumped polariton laser operating at room temperature. A maximum -3 dB modulation bandwidth of 1.18 GHz is measured. The experimental results have been analyzed with a theoretical model based on the Boltzmann kinetic equations and the agreement is very good. We have also investigated frequency chirping during such modulation. Gain compression phenomenon in a polariton laser is interpreted and a value is obtained for the gain compression factor. PMID- 26154684 TI - An evaluation of low back pain among female brick field workers of West Bengal, India. AB - OBJECTIVES: The purpose of the study was to determine the prevalence of low back pain (LBP) among brick field workers and to explore attributed causes of LBP, investigate the relationship between LBP and psychophysical and psychosocial factors and measure the impact of LBP. METHODS: A modified Nordic Musculoskeletal Disorder Questionnaire along with Body Part Discomfort scale were administered to brick field workers (N = 148). Working posture of the participants was assessed using Rapid Entire Body Assessment (REBA) method. RESULTS: The study showed that 70 % of the female workers reported LBP due to awkward working posture for prolonged period of time. This was mainly reported by brick moulders. 45 % reported LBP due to manual material handling (MMH) and 40 % due to awkward lifting of heavy objects (brick). The study shows that the LBP is more prevalent (OR 1.59 and 95 % CI 0.411-6.207). 78 % of the female workers want the job rotation to relieve from their job monotony. CONCLUSIONS: LBP occurred among female workers due to awkward posture, repetitive work and MMH. This study also stated that psychosocial cause of LBP is inadequacy income, monotony work, job dissatisfaction. Working posture analysis REBA suggests that all the working postures are high-risk level. PMID- 26154685 TI - Excited-State Intramolecular Proton Transfer of the Natural Product Quercetin. AB - Intramolecular proton-transfer dynamics in the lowest excited state (ESIHT) were studied in the natural product quercetin. We found that in all seven solvents used in this study, the ESIHT rate is ultrafast. We estimate that the ESIHT rate is about 70 fs or less. We found that in deuterated protic solvents, such as methanol-d or ethanol-d, the ESIHT rate is slower and the proton-transfer time constant is about 110 fs. The tautomeric form fluorescence quantum yield of quercetin is very low, of the order of the normal form. PMID- 26154683 TI - High dose cytarabine, mitoxantrone and l-asparaginase (HAMA) salvage for relapsed or refractory acute myeloid leukemia (AML) in the elderly. AB - Acute myeloid leukemia (AML) is an aggressive malignancy that affects older patients. The role of salvage therapy in the elderly is controversial and there is little data on efficacy. Outcomes for 94 relapsed or refractory AML patients who received salvage HAMA therapy were analyzed. Of the 94 patients 66 were >=60, including 26 patients >=70, and 28 were <60 years old. Early mortality (30-day) was 14% (4%<60, 18%>=60 years old). Overall, 27% of patients died during hospitalization or were discharged to hospice (11%<60, 33%>=60 years old). CR/CRi was achieved in 41% of patients (61%<60, 33%>=60 years old). Median survival was 6.1 months (15.7<60, 5.2>=60). Patients >=60 who achieved a CR/CRi had a median survival of 11.7 months. At 12 months 56% of patients <60 were alive versus 24% of patients >=60. At 24 months these numbers fell to 40% and 2% respectively. In those <60 years old, 50% went on to allogeneic hematopoietic stem cell transplant (HSCT) whereas 14% of patients in the >=60 cohort did so. In conclusion, HAMA salvage therapy results in a 33% response rate in patients >=60 years old with acceptable toxicity. PMID- 26154687 TI - Energy Transfer Assays Using Quantum Dot-Gold Nanoparticle Complexes: Optimizing Oligonucleotide Assay Configuration Using Monovalently Conjugated Quantum Dots. AB - The energy transfer between quantum dots (QDs) and gold nanoparticles (AuNPs) represents a popular transduction scheme in analytical assays that use nanomaterials. The impact of the spatial arrangement of the two types of nanoparticles on analytical performance has now been evaluated using a nucleic acid strand displacement assay. The first spatial arrangement (configuration 1) involved the assembly of a number of monovalently functionalized QD oligonucleotide conjugates around a single central AuNP that was functionalized with complementary oligonucleotide sequences. The assembly of these complexes, and subsequent disassembly via target oligonucleotide-mediated displacement, were used to evaluate energy transfer efficiencies. Furthermore, the inner filter effect of AuNPs on the fluorescence intensity of the QD was studied. AuNPs of three different diameters (6, 13, and 30 nm) were used in these studies. Configuration 2 was based on the placement of monovalently functionalized AuNP oligonucleotide conjugates around a single QD that was functionalized with a complementary oligonucleotide. The optimal assay configuration, established by evaluating energy transfer efficiencies and inner filter effects, was obtained by arranging at most 15 QDs around the 13 nm AuNP (configuration 1). These assays provided a 2.5-fold change in fluorescence intensity in the presence of target oligonucleotides. To obtain the same response with configuration 2 required the placement of three 6 nm AuNPs around the QD. This resulted in configuration 2 having a 5-fold lower fluorescence intensity when compared to configuration 1. The use of low-cost detection systems (digital camera) further emphasized the higher analytical performance of configuration 1. Response curves obtained using these detection systems demonstrated that configuration 1 had a 10-fold higher sensitivity when compared to configuration 2. This study provides an important framework for the development of sensitive assays using gold nanoparticles and quantum dots. PMID- 26154686 TI - Clinicopathological and genetic heterogeneity of the head and neck solitary fibrous tumours: a comparative histological, immunohistochemical and molecular study of 36 cases. AB - AIMS: Solitary fibrous tumour (SFT) harbours recurrent inv12(q13q13)-derived NAB2 STAT6 fusions, resulting in STAT6 nuclear expression. SFTs affecting the head and neck are rare, for which we reported their clinicopathological, immunohistochemical, and genetic features. METHODS AND RESULTS: With 19 cases assessable for NAB2-STAT6 fusions, 36 head and neck SFTs (18 males; 18 females) diagnosed between 13 and 79 years (median, 47 years) of age were analysed for clinicopathological features and STAT6 immunoexpression. These SFTs, ranging from 5 to 80 mm (median, 25 mm), affected the oral cavity/pharynx (12), orbit (11), sinonasal structures (seven), and somatic soft tissues or skull (six). Histologically, 20 SFTs were conventional, six were giant-cell angiofibroma-like, one was fat-forming, four were cellular/atypical, and five were malignant (two developing metastases). STAT6 distinctively decorated the tumoral nuclei in 35 (97.2%) SFTs, but not in 29 site-relevant histological mimics categorized into 12 entities. Sixteen (84.2%) SFTs showed NAB2-STAT6 fusions with highly heterogeneous exon compositions, including NAB2ex6-STAT6ex17 in four cases, NAB2ex4-STAT6ex2 in three cases, NAB2ex2-STAT6ex2, NAB2ex4-STAT6ex4, NAB2ex6 STAT6ex16 and NAB2ex6-STAT6ex18 in two cases each, and NAB2ex3-STAT6ex19 in one case. CONCLUSIONS: Nuclear STAT6 immunoexpression is sensitive and specific for distinguishing SFT from mimics. However, considerable heterogeneity exists in the head and neck SFTs regarding the locations, histological patterns, and NAB2-STAT6 fusion variants. PMID- 26154688 TI - Pd(0)-Catalyzed Cross-Coupling of 1,1-Diboronates with 2,2'-Dibromobiphenyls: Synthesis of 9H-Fluorenes. AB - An efficient and mild synthesis of 9H-fluorene derivatives through a Pd(0) catalyzed cross-coupling reaction of 1,1-diboronates with 2,2'-dibromobiphenyls has been developed. This reaction features high yields, operational simplicity, and mild reaction conditions, thus providing an excellent alternative to published methods for 9H-fluorene synthesis. PMID- 26154689 TI - Agreement between Automated and Traditional Measures of Tear Film Breakup. AB - PURPOSE: To determine the repeatability and agreement between the noninvasive Keratograph tear break-up time (NIK-BUT) as measured by the Oculus Keratograph 4 and fluorescein tear break-up time (FBUT). METHODS: Sixty subjects were recruited for two study visits separated by 7 (+/- 2) days. At each visit, three NIK-BUT measures and FBUT measures were obtained. Each NIK-BUT measure from the Keratograph included a first and an average NIK-BUT. The means of the measures obtained, first NIK-BUT, and average NIK-BUT and FBUT were calculated for each visit. Between- and within-visit agreement was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman 95% limits of agreement (LoA) analyses of log-transformed data. RESULTS: Between-visit ICCs were 0.53 [95% confidence interval (CI), 0.32 to 0.69] for first NIK-BUT, 0.59 (95% CI, 0.40 to 0.73) for average NIK-BUT, and 0.66 (95% CI, 0.49 to 0.78) for FBUT, whereas 95% LoA were -0.65 to 0.67, -0.44 to 0.48, and -1.14 to 1.10 [back transformed: (visit 1 + 0.01)/(visit 2 + 0.01) = 0.22 to 4.68, 0.36 to 3.02, and 0.07 to 12.59] for the aforementioned methods, respectively. The visit 1 within-visit ICC between first NIK-BUT and FBUT was 0.44 (95% CI, 0.21 to 0.62), whereas the 95% LoA was -0.84 to 1.18 [back transformed: (first NIK-BUT + 0.01)/(FBUT + 0.01) = 0.14 to 15.14]. Likewise, the visit 1 within-visit ICC between average NIK-BUT and FBUT was 0.41 (95% CI, 0.18 to 0.60), whereas the 95% LoA was -0.58 to 1.44 [back transformed: (average NIK-BUT + 0.01)/(FBUT + 0.01) = 0.26 to 27.54]. CONCLUSIONS: The 95% LoA suggest that the average NIK-BUT has better between visit agreement compared with the first NIK-BUT or FBUT. The first NIK-BUT showed better within-visit agreement with the FBUT than the average NIK-BUT. In addition, there is better between- and within-visit agreement for all measures at lower values. PMID- 26154690 TI - Associations with Meibomian Gland Atrophy in Daily Contact Lens Wearers. AB - PURPOSE: To determine associations for contact lenses (CLs) and meibomian gland atrophy in a matched-pair study. METHODS: Contact lens wearers (case) and age- and sex-matched non-contact lens (NCL) wearers with no history of CL use (control) were recruited for a multicenter study. All subjects were administered the Ocular Surface Disease Index questionnaire and a comprehensive battery of clinical tests (e.g., tear breakup time, bulbar and limbal redness, meibography, etc.) were performed. Upper and lower eyelid meibomian gland atrophy were graded with both digital meibography (percent gland atrophy) and visual meiboscore methods. Conditional logistic regression analyses were then used to determine relationships among CL use, meibomian gland atrophy, and ocular surface signs and symptoms. RESULTS: A total of 70 matched pairs were analyzed. The mean (+/- SD) age of the CL group was 30.6 (+/- 12.4) years, and that of the NCL group was 30.1 (+/- 12.2) years. The subjects were 63% female. The association between CL wear and meiboscore was not significant univariately, but the best-fitting multivariate regression model showed that higher meiboscores were associated with being a CL wearer (odds ratio [OR], 2.45) in a model that included eyelid margin erythema (OR, 0.25) and lissamine green staining (OR, 1.25). Percent gland atrophy was not associated with CL wear in regression analysis (p = 0.31). CONCLUSIONS: This study determined inconclusive associations with CLs and meibomian gland atrophy. This study also provided a comprehensive assessment of differences between CL and NCL wearers. PMID- 26154691 TI - Corneal Neuralgia after LASIK. AB - PURPOSE: To illustrate that corneal neuralgia may be the basis for refractory dry eye syndrome after laser-assisted in situ keratomileusis (LASIK). METHODS: The methodology used is that of a retrospective medical record review of a small case series. RESULTS: Three male patients, aged 30 to 48 years, referred in 2012 for dry eye syndrome refractory to treatment within 1 year of LASIK or LASIK enhancement are reported. Each patient gave history of eye pain, light sensitivity, and difficulty with visual activities beginning within 2 months of LASIK or LASIK enhancement. Best-corrected visual acuity was 20/15 or 20/20 in each of the six eyes. Tear-centered models and metrics did not explain persistent symptoms, which was consistent with inadequate response to standard dry eye treatments used before referral and reported here. In vivo confocal microscopy was abnormal at presentation in each case and was followed over time. Treatments undertaken subsequent to referral included autologous serum tears (three cases), PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem) treatment (two cases), and systemic agents for pain, anxiety, or depression (three cases). By the end of 2013, at a mean of 23 months after LASIK or LASIK enhancement, symptoms improved in all three patients. CONCLUSIONS: Patients with persistent dry eye symptoms out of proportion to clinical signs after LASIK have a syndrome that may best be classified as corneal neuralgia. In vivo confocal microscopy can be informative as to the neuropathic basis of this condition. In keeping with current understanding of complex regional pain syndrome, early multimodal treatment directed toward reducing peripheral nociceptive signaling is warranted to avoid subsequent centralization and persistence of pain. Distinguishing this syndrome from typical post-LASIK dry eye remains a challenge. PMID- 26154692 TI - Effects of Isotretinoin on Meibomian Glands. AB - The authors have reviewed the potential etiology and long-standing consequences of isotretinoin use in the development of dry eye symptoms in the absence of significant clinical findings. Despite the normal appearance of meibomian gland structure on meibography and minimal signs of eyelid margin inflammation, the secretory function of these glands is reduced and symptoms of dryness can greatly impact a patient's quality of life. The available literature indicates that isotretinoin's effect on the meibomian glands likely mimics its effects on the sebaceous glands of the skin in the treatment of acne. Several representative cases seen at the University of California Berkeley School of Optometry Dry Eye Clinic provide a clinical paradigm with the goal of raising awareness of the potential prevalence of this disease in patients who experience symptoms of dry eye. These cases highlight the importance of meibomian gland expression in determining whether there is poor quality and/or quantity of meibum secondary to reduced gland function. Currently, there is no definitive method to restore the structure and function of damaged meibomian glands; thus, treatment options for isotretinoin-associated meibomian gland dysfunction are primarily palliative to manage patient symptoms. PMID- 26154694 TI - ELISA-Confirmed Bilateral Ocular Toxocariasis with Different Features. AB - PURPOSE: To report a rare case of bilateral ocular toxocariasis with a different clinical presentation in each eye. CASE REPORT: A 56-year-old man presented with severe ocular pain and acute visual loss in the right eye (RE). His best corrected visual acuity was hand motion in the RE and 20/30 in the left eye (LE). Slit-lamp examination showed a severe anterior chamber reaction in the RE and a moderate anterior chamber reaction in the LE. The fundus of the LE showed a posterior hemorrhagic granuloma with vascular sheathing whereas the fundus of the RE was not visible because of severe vitreous opacification. Blood laboratory testing disclosed hyperproduction of IgE but no eosinophilia. Serum enzyme-linked immunosorbent assay testing was positive for Toxocara canis IgG (1:38). Toxocara antibody was also detected in the aqueous humor from both eyes (RE, 1:321; LE, 1:254). The patient was treated with topical and oral steroids along with oral albendazole. Additionally, phacoemulsification, a therapeutic vitrectomy, and vitreous cultures were performed in the RE. During the vitrectomy, the fundus of the RE showed diffuse retinal vascular obstruction with sheathing. Toxocara antibodies were detected in the vitreous fluid from the RE (1:679). A laser barrier was placed around the granuloma in the LE. After 1 month of steroid therapy, a tapering schedule was started. At 6 months postoperatively, the fundi of both eyes were stable. The final best-corrected visual acuity was 8/20 in the RE and 20/20 in the LE. CONCLUSIONS: A rare case of bilateral ocular toxocariasis is reported with a different clinical presentation in each eye that was diagnosed using enzyme-linked immunosorbent assay analysis of intraocular fluids. Both eyes were successfully treated medically with a vitrectomy eventually being required in the RE. PMID- 26154693 TI - Relationships among Tear Film Stability, Osmolarity, and Dryness Symptoms. AB - PURPOSE: To examine the relationships among tear osmolarity, tear film stability, and several measures of dry eye (DE) symptoms in a multivariable analysis. METHODS: A cross-sectional study was conducted with 137 subjects (68 non-contact lens [CL] wearers and 69 soft CL wearers) recruited from a university campus. Tear breakup time (TBUT) was measured noninvasively (NITBUT) and with fluorescein (FTBUT). Tear osmolarity was measured by an osmometer. Dry eye symptoms were assessed using the Dry Eye Flow Chart and several different questionnaires. RESULTS: Subjects ranged in age from 18 to 67 years, with a mean of 28 years. Subjects had a mean (SD) osmolarity of 293 (10) mOsm/L, NITBUT of 14.1 (10.9) seconds, and FTBUT of 14.8 (12.6) seconds. Shorter NITBUT and FTBUT were significantly associated with female sex (p = 0.001 and p = 0.027, respectively) and Asian ethnicity (p = 0.030 and p = 0.004, respectively). There were no clinically significant relationships between tear osmolarity and FTBUT, NITBUT, or DE symptoms. Higher Dry Eye Flow Chart score (i.e., worse symptoms) was associated with older age (p < 0.001), female sex (p = 0.014), CL wear (p < 0.001), shorter NITBUT (p < 0.001), and shorter FTBUT (p = 0.028). The sensitivities and specificities for using clinical measurements to diagnose moderate to severe DE were as follows: osmolarity, 0.67 and 0.46, respectively; NITBUT, 0.72 and 0.52, respectively; and FTBUT, 0.68 and 0.57, respectively. CONCLUSIONS: In a population of asymptomatic, mild and moderate DE patients, increased tear osmolarity was not significantly associated with reported symptom severity and frequency. Tear osmolarity, NITBUT, and FTBUT exhibited similar sensitivities and specificities when used to diagnose moderate to severe DE. PMID- 26154695 TI - Repair of rat cranial bone defect by using bone morphogenetic protein-2-related peptide combined with microspheres composed of polylactic acid/polyglycolic acid copolymer and chitosan. AB - The effects of the transplanted bone morphogenetic protein-2 (BMP2) -related peptide P24 and rhBMP2 combined with poly(lactic-co-glycolic acid) (PLGA)/chitosan (CS) microspheres were investigated in promoting the repair of rat cranial bone defect. Forty white rats were selected and equally divided into four groups (group A: 1 MUg of rhBMP2/PLGA/CS composite; group B: 3 mg of P24/PLGA/CS composite; group C: 0.5 MUg of rhBMP2 + 1.5 mg of P24/PLGA/CS composite; group D: blank PLGA/CS material), and rat cranial bone defect models with a diameter of 5 mm were established. The materials were transplanted to the cranial bone defects. The animals were sacrificed on weeks 6 and 12 post operation. Radiographic examinations (x-ray imaging and 3D CT scanning) and histological evaluations were performed. The repaired areas of cranial bone defects were measured, and the osteogenetic abilities of various materials were compared. Cranial histology, imaging, and repaired area measurements showed that the osteogenetic effects at two time points (weeks 6 and 12) in group C were better than those in groups A and B. The effects in groups A and B were similar. Group D achieved the worst repair effect of cranial bone defects, where a large number of fibrous connective tissues were observed. The PLGA/CS composite microspheres loaded with rhBMP2 and P24 had optimal concrescence and could mutually increase their osteogenesis capability. rhBMP2 + P24/PLGA/CS composite is a novel material for bone defect repair with stable activity to induce bone formation. PMID- 26154697 TI - Performance of an anaerobic, static bed, fixed film bioreactor for chlorinated solvent treatment. AB - Anaerobic, fixed film, bioreactors bioaugmented with a dechlorinating microbial consortium were evaluated as a potential technology for cost effective, sustainable, and reliable treatment of mixed chlorinated ethanes and ethenes in groundwater from a large groundwater recovery system. Bench- and pilot-scale testing at about 3 and 13,500 L, respectively, demonstrated that total chlorinated solvent removal to less than the permitted discharge limit of 100 MUg/L. Various planned and unexpected upsets, interruptions, and changes demonstrated the robustness and reliability of the bioreactor system, which handled the operational variations with no observable change in performance. Key operating parameters included an adequately long hydraulic retention time for the surface area, a constant supply of electron donor, pH control with a buffer to minimize pH variance, an oxidation reduction potential of approximately -200 millivolts or lower, and a well-adapted biomass capable of degrading the full suite of chlorinated solvents in the groundwater. Results indicated that the current discharge criteria can be met using a bioreactor technology that is less complex and has less downtime than the sorption based technology currently being used to treat the groundwater. PMID- 26154696 TI - Hydrogen Sulfide Attenuates Inflammatory Hepcidin by Reducing IL-6 Secretion and Promoting SIRT1-Mediated STAT3 Deacetylation. AB - AIMS: Anemia of inflammation is quite prevalent in hospitalized patients with poor prognosis. Concerns about the effectiveness and safety of iron supplementation have arisen, driving the demand for alternative therapies. Induction of hepatic hepcidin, the master hormone of iron homeostasis, causes anemia under inflammatory conditions. Previous studies indicated that hydrogen sulfide (H2S), the third gasotransmitter and a well-known regulator of inflammation, may inhibit the secretion of inflammatory cytokines. We thus investigated the effect of H2S on inflammatory hepcidin induction. RESULTS: H2S suppressed lipopolysaccharide (LPS)-induced hepcidin production and regulated iron homeostasis in mice by decreasing serum interleukin-6 (IL-6) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) activation; similar results were obtained in Huh7 cells exposed to conditioned medium from LPS-challenged THP-1 macrophages. Intriguingly, we found H2S also attenuated hepcidin levels in Huh7 cells and mouse primary hepatocytes in a sirtuin 1 (SIRT1)-dependent manner. By promoting SIRT1 expression and stabilizing SIRT1-STAT3 interactions, H2S ameliorated IL-6-induced STAT3 acetylation, resulting in reduced hepcidin production. Inhibition and silencing of SIRT1 diminished H2S-mediated suppression of hepcidin, as opposed to SIRT1 activation and overexpression. Consistent results were observed in vivo. Furthermore, knockout of cystathionine gamma-lyase (CSE), an endogenous H2S synthase, exaggerated inflammatory hepcidin expression in mice. INNOVATION: For the first time, we elucidated the effects and possible mechanisms of H2S on inflammatory hepcidin and established a novel regulatory link between SIRT1 and hepcidin. CONCLUSION: Our work demonstrates that H2S attenuates inflammation-induced hepatic hepcidin via multipathways and suggests new treatment strategies for anemia of inflammation. PMID- 26154699 TI - Control of the initial growth in atomic layer deposition of Pt films by surface pretreatment. AB - The controllability of the nucleation behavior of Pt in atomic layer deposition (ALD) by surface pretreatments with H2O, H2S, and NH3 was investigated. The H2O pretreatment on SiO2 and TiO2 surfaces had little effect on the nucleation of Pt. The H2S pretreatment on the SiO2 and TiO2 surfaces significantly delayed the nucleation of Pt on them, while the NH3 pretreatment on the TiO2 surface led to fluent nucleation of Pt. In particular, a continuous Pt film was successfully formed even at an ultrathin thickness of approximately 2.2 nm by NH3 pretreatment. This work suggests that the pretreatment with H2S and NH3 is an efficient way to control the nucleation of Pt in ALD without the support of any reactive species, such as plasma or O3. Such a strategy enables the easy control of the size and distribution density of Pt nanoparticles for a wide range of applications. PMID- 26154700 TI - Periprosthetic Anesthetic for Postoperative Pain After Laparoscopic Ventral Hernia Repair: A Randomized Clinical Trial. AB - IMPORTANCE: Laparoscopic ventral hernia repair (LVHR) using mesh is a well established intervention for ventral hernia, but pain control can be challenging. OBJECTIVE: To determine whether instillation of a long-acting local anesthetic between the mesh and the peritoneum after LVHR reduces pain or narcotic requirements. DESIGN, SETTING, AND PARTICIPANTS: A prospective, double-blind, randomized clinical trial with data collection during a brief hospital stay in a tertiary care, community teaching hospital over 3 years between December 15, 2011, and March 28, 2014. Of 120 screened patients undergoing LVHR in this intention-to-treat analysis, 99 eligible patients were randomized. Forty-two patients received the study drug, and 38 patients received placebo. Patients with a history of chronic narcotic use were excluded. INTERVENTION: After mesh placement, a long-acting local anesthetic (bupivacaine hydrochloride, 0.50%) or placebo (0.9% normal saline) was injected between the mesh and the peritoneum. MAIN OUTCOMES AND MEASURES: Postoperative pain (on a standard scale ranging from 0 to 10), and narcotic medication use (intravenous morphine equivalents). There were no adverse events. RESULTS: Baseline and operative characteristics were similar except that the treatment group was older (61.8 vs 52.3 years, P = .001). After surgery, pain scores in the recovery room (3.2 vs 4.7, P = .003), interval total narcotic use (6.7 vs 12.5 mg, P = .003 at <4 hours and 0 vs 2.7 mg, P = .01 at 8-12 hours), and total intravenous narcotic use (9.2 vs 17.2 mg of morphine sulfate equivalents, P = .03) were significantly less in the treatment group. CONCLUSIONS AND RELEVANCE: Administration of a long-acting local anesthetic between the mesh and the peritoneum significantly reduces postoperative pain and narcotic use after LVHR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01530815. PMID- 26154701 TI - Choroidal neovascularization, outer retinal tubulation and fundus autofluorescence findings in a patient with enhanced S-cone syndrome. PMID- 26154702 TI - Combinations of gene ontology and pathway characterize and predict prognosis genes for recurrence of gastric cancer after surgery. AB - Gastric cancer (GC) is the second leading cause of death from cancer globally. The most common cause of GC is the infection of Helicobacter pylori, but ~11% of cases are caused by genetic factors. However, recurrences occur in approximately one-third of stage II GC patients, even if they are treated with adjuvant chemotherapy or chemoradiotherapy. This is potentially due to expression variation of genes; some candidate prognostic genes were identified in patients with high-risk recurrences. The objective of this study was to develop an effective computational method for meaningfully interpreting these GC-related genes and accurately predicting novel prognostic genes for high-risk recurrence patients. We employed properties of genes (gene ontology [GO] and KEGG pathway information) as features to characterize GC-related genes. We obtained an optimal set of features for interpreting these genes. By applying the minimum redundancy maximum relevance algorithm, we predicted the GC-related genes. With the same approach, we further predicted the genes for the prognostic of high-risk recurrence. We obtained 1104 GO terms and KEGG pathways and 530 GO terms and KEGG pathways, respectively, that characterized GC-related genes and recurrence related genes well. Finally, three novel prognostic genes were predicted to help supplement genetic markers of high-risk GC patients for recurrence after surgery. An in-depth text mining indicated that the results are quite consistent with previous knowledge. Survival analysis of patients confirmed the novel prognostic genes as markers. By analyzing the related genes, we developed a systematic method to interpret the possible underlying mechanism of GC. The novel prognostic genes facilitate the understanding and therapy of GC recurrences after surgery. PMID- 26154703 TI - Experimental study of the characteristics of a novel mesh suture. AB - BACKGROUND: The failure of sutures to maintain tissue in apposition is well characterized in hernia repairs. A mesh suture designed to facilitate tissue integration into and around the filaments may improve tissue hold and decrease suture pull-through. METHODS: In vitro, the sutures were compared for resistance to pull-through in ballistics gel. In vivo, closure of midline laparotomy incisions was done with both sutures in 11 female pigs. Tissue segments were subsequently subjected to mechanical and histological testing. RESULTS: The mesh suture had tensile characteristics nearly identical to those of 0-polypropylene suture. Mesh suture demonstrated greater resistance to pull-through than standard suture (mean(s.d.) 4.27(0.42) versus 2.23(0.48) N; P < 0.001) in vitro. In pigs, the ultimate tensile strength for repaired linea alba at 8 days was higher with mesh suture (320(57) versus 160(56) N; P < 0.001), as was the work to failure (24.6(14.2) versus 7.3(3.7) J; P < 0.001) and elasticity (128(9) versus 72(7) N/cm; P < 0.001) in comparison with 0-polypropylene suture. Histological examination at 8 and 90 days showed complete tissue integration of the mesh suture. CONCLUSION: The novel mesh suture structure increased the strength of early wound healing in an experimental model. Surgical relevance Traditional sutures have the significant drawback of cutting and pulling through tissues in high-tension closures. A new mesh suture design with a flexible macroporous outer wall and a hollow core allows the tissues to grow into the suture, improving early wound strength and decreasing suture pull-through. This technology may dramatically increase the reliability of high-tension closures, thereby preventing incisional hernia after laparotomy. As suture pull-through is a problem relevant to all surgical disciplines, numerous additional indications are envisioned with mesh suture formulations of different physical properties and materials. PMID- 26154704 TI - Explaining the Decrease of In-Hospital Mortality from Ischemic Stroke. AB - BACKGROUND: Mortality from ischemic stroke has declined over time. However, little is known about the reasons for the decreased mortality. We therefore aimed to evaluate trends in in-hospital mortality and to identify factors associated with these trends. METHODS: This study was based on a prospective database of 26 hospitals of the Stroke Register of Northwestern Germany, which included 73,614 patients admitted between 2000 and 2011. Time trends in observed (crude) and risk adjusted in-hospital mortality were assessed. Independent factors associated with death after stroke were evaluated using multivariable logistic regression analysis. RESULTS: The observed in-hospital mortality decreased from 6.6% in 2000 to 4.6% in 2008 (P < 0.001 for trend) and then remained fairly stable. The risk adjusted mortality decreased from 2.85% in 2000 to 1.86% in 2008 (P < 0.01 for trend) and then increased to 2.32% in 2011. Use of in-hospital treatments including antiplatelets within 48 hours, antihypertensive therapy, statins, antidiabetics, physiotherapy and anticoagulants increased over time and was significantly associated with a decrease in mortality. The association of the year of admission with mortality became insignificant after adjustment for antiplatelet therapy within 48 hours (from OR 0.96; 95% CI, 0.94-0.98, to OR 0.99; 95% CI, 0.97-1.01) and physiotherapy (from OR 0.96; 95% CI, 0.94-0.97, to OR 0.99; 95% CI, 0.97-1.00). CONCLUSIONS: In-hospital mortality decreased by approximately one third between 2000 and 2008. This decline was paralleled by improvements in different in-hospital managements, and we demonstrated that it was partly mediated by early antiplatelet therapy and physiotherapy use. PMID- 26154705 TI - Effect of Caseinophosphopeptides from alphas- and beta-Casein on Iron Bioavailability in HuH7 Cells. AB - Two pools of caseinophosphopeptides (CPPs) obtained from alphas- and beta-casein fractions (alpha-CPPs and beta-CPPs) were characterized. A total of 16 CPPs were identified in the alpha-CPPs pool, 9 of them derived from alphas1-casein and 7 from alphas2-casein. A total of 18 CPPs were identified in the beta-CPPs pool. Four of the identified CPPs contained the characteristic phosphoseryl-glutamic acid cluster SpSpSpEE. Calcein assay was used to compare the iron-binding capacity of the alpha- and beta-CPPs pools. At the concentration of 12.5 MUM CPPs used in the iron bioavailability assays, beta-CPPs pools show greater iron binding capacity than alpha-CPPs pools. HuH7 human hepatoma cells show many differentiated functions of liver cells in vivo and can be used to evaluate iron bioavailability (ferritin content and soluble transferrin receptor) from Fe-alpha CPPs and Fe-beta-CPPs complexes. The alpha-CPPs and beta-CPPs pools did not improve ferritin content or soluble transferrin receptor in HuH7 cells. PMID- 26154707 TI - New insights in the management of patients with hairy cell leukemia. AB - PURPOSE OF REVIEW: Although hairy cell leukemia (HCL) was identified in 1958 by Bouroncle and colleagues, HCL remains in 2015 a mysterious disease. Accurate diagnosis of HCL relies on the recognition of hairy cells by morphology and flow cytometry in blood and/or bone marrow. However, there are cases difficult to diagnose, particularly in variants of HCL. Furthermore, some diseases such as splenic diffuse red pulp small B-cell lymphoma are very close to HCL and may be misdiagnosed. Major advances in the management of patients who have HCL have been made following the use of purine nucleoside analogs. However, new treatment options can be available in relapsed/refractory HCL: monoclonal antibody therapy, BRAF inhibitors, or immunotoxins. RECENT FINDINGS: The presence of the BRAFV600E mutation was recently identified in most cases of HCL and its absence in variants of HCL and in other B-cell chronic lymphoproliferative disorders. The precise cellular origin of HCL remains elusive but BRAF mutations were detected in hematopoietic stem cells of patients with HCL. Assessment for minimal residual disease is important in clinical trials. Minimal residual disease detection can clearly predict inferior long-term outcomes or early relapses in patients with HCL. Recent reports have shown that inhibition of BRAF kinase by drugs such as vemurafenib is effective in relapsed/refractory HCL. Immunotoxins offer new opportunities even in patients without BRAF mutations. SUMMARY: All these findings have major implications for diagnosis, monitoring, and treatment of HCL and variant forms of HCL. PMID- 26154706 TI - Causative role of left aIPS in coding shared goals during human-avatar complementary joint actions. AB - Successful motor interactions require agents to anticipate what a partner is doing in order to predictively adjust their own movements. Although the neural underpinnings of the ability to predict others' action goals have been well explored during passive action observation, no study has yet clarified any critical neural substrate supporting interpersonal coordination during active, non-imitative (complementary) interactions. Here, we combine non-invasive inhibitory brain stimulation (continuous Theta Burst Stimulation) with a novel human-avatar interaction task to investigate a causal role for higher-order motor cortical regions in supporting the ability to predict and adapt to others' actions. We demonstrate that inhibition of left anterior intraparietal sulcus (aIPS), but not ventral premotor cortex, selectively impaired individuals' performance during complementary interactions. Thus, in addition to coding observed and executed action goals, aIPS is crucial in coding 'shared goals', that is, integrating predictions about one's and others' complementary actions. PMID- 26154708 TI - Management of elderly patients with chronic lymphocytic leukemia in the era of targeted therapies. AB - PURPOSE OF REVIEW: Chronic lymphocytic leukemia (CLL) is frequently diagnosed after 71 years, though median age in published clinical trials with standard chemoimmunotherapy regimens in frontline or relapse setting is mostly below 70 years (58-71 years). Development of oral, less toxic and thus more affordable targeted therapies offers new therapeutic options in those patients deemed unfit for chemotherapy. RECENT FINDINGS: This review will discuss results of these new agents in the therapy of elderly patients. Apart from discussing the impact of chronological age, creatinine clearance and cumulative illness rating scale scores in the clinical outcomes, we will also discuss how individualized treatment decision-making should include more precise geriatric assessment tools to thoroughly assess life expectancy, anticipate tolerability, to avoid deleterious stress precipitating prefrail patients into definitive loss of capacity, with dramatic social and economic costs. SUMMARY: In the era of new targeted agents to fight cancers, we propose concepts to help us understand how elderly dedicated trial designs and geriatric assessment tools (apart from the evaluation of CLL biological risk factors) will undoubtedly revolutionize therapeutic approaches in everyday practice CLL patients. PMID- 26154709 TI - Fabrication of Mesoporous CoS2 Nanotube Arrays as the Counter Electrodes of Dye Sensitized Solar Cells. AB - Mesoporous cobalt sulfide nanotube arrays on FTO-coated glass were synthesized by combining three simple technologies: the selective etching of ZnO sacrificial templates, mesoporous Co3 O4 formation from cobalt-chelated chitosan, and ion exchange reaction (IER). The mesoporous Co3 O4 nanotubes composed of the Co3 O4 nanoparticles possess a high surface area and are taken advantage for further removal of templates and IER. The morphologies and crystal structures of the CoS2 nanotube arrays were characterized by SEM, TEM, and XRD analyses. Their electrocatalytic properties were determined by electrochemical analyses including cyclic voltammetry measurements and Tafel polarization. The DSSCs assembled with a CoS2 counter electrode achieved a power conversion efficiency of 6.13 %, which was comparable to that of the DSSC with the Pt counter electrode (6.04 %). This indicates that the mesoporous CoS2 nanotube array can be a low-cost and efficient alternative for the reduction of electrolytes in DSSCs. PMID- 26154710 TI - Automated office blood pressure - being alone and not location is what matters most. AB - OBJECTIVE: Measurement of office blood pressure using a fully automated sphygmomanometer that takes multiple readings with the patient resting quietly alone has been called automated office blood pressure (AOBP). Almost all AOBP research has involved the patient resting alone in an examining room, which is often impractical in a clinical setting. The possibility that valid AOBP readings can be obtained with the patient resting quietly in a waiting room was examined. METHODS: AOBP readings using the BpTRU device recorded with the patient resting quietly in the waiting room were obtained in patients referred for ambulatory BP monitoring. The relationship between the AOBP and the awake ambulatory blood pressure (AABP) (mmHg) was examined. RESULTS: In 422 patients, the mean (+/-SD) AABP (139.4+/-13.4/80.7+/-10.6) was similar to the mean AOBP recorded in the waiting room (140.5+/-19.8/83.1+/-11.2), with both values being significantly lower than a single office BP (155.1+/-18.7/90.2+/-12.7) taken by a nurse. In the 178 untreated patients, the mean systolic AOBP and AABP were almost identical, with the diastolic AOBP being 1.5 mmHg higher. Bland-Altman plots for systolic BP showed a relatively consistent relationship for AOBP versus the AABP over the range of BPs recorded. The sensitivity, specificity, and accuracy for AOBP versus AABP were comparable with the values obtained with AOBP recorded previously in an examining room. CONCLUSION: AOBP readings recorded in a waiting room are comparable with the AABP, making it possible to obtain AOBP in clinical practice without the need to occupy an examining room. PMID- 26154711 TI - Quantifying the Intra-Regional Precipitation Variability in Northwestern China over the Past 1,400 Years. AB - There has been a surge of paleo-climatic/environmental studies of Northwestern China (NW China), a region characterized by a diverse assortment of hydro climatic systems. Their common approach, however, focuses on "deducing regional resemblance" rather than "exploring regional variance." To date, efforts to produce a quantitative assessment of long-term intra-regional precipitation variability (IRPV) in NW China has been inadequate. In the present study, we base on historical flood/drought records to compile a decadal IRPV index for NW China spanned AD580-1979 and to find its major determinants via wavelet analysis. Results show that our IRPV index captures the footprints of internal hydro climatic disparity in NW China. In addition, we find distinct ~120-200 year periodicities in the IRPV index over the Little Ice Age, which are attributable to the change of hydro-climatic influence of ocean-atmospheric modes during the period. Also, we offer statistical evidence of El Nino Southern Oscillation (Indo Pacific warm pool sea surface temperature and China-wide land surface temperature) as the prominent multi-decadal to centennial (centennial to multi centennial) determinant of the IRPV in NW China. The present study contributes to the quantitative validation of the long-term IRPV in NW China and its driving forces, covering the periods with and without instrumental records. It may help to comprehend the complex hydro-climatic regimes in the region. PMID- 26154712 TI - Rapid Access to 3-Aminoindazoles from Tertiary Amides. AB - A two-step synthesis of structurally diverse 3-aminoindazoles from readily available starting materials was developed. This sequence includes a one-pot synthesis of aminohydrazones through chemoselective Tf2O-mediated activation of tertiary amides and subsequent addition of nucleophilic hydrazides. These precursors then participate in an intramolecular ligand-free Pd-catalyzed C-H amination reaction. The azaheterocycles synthesized via this approach were further diversified through subsequent deprotection/functionalization reactions. PMID- 26154713 TI - A Systematic Evaluation of the QTc Interval and Antidepressants in Youth: An Electronic Health Record Study. AB - OBJECTIVE: The US Food and Drug Administration announced that citalopram was associated with dose-related prolongation of the QTc interval in adults. This study aimed to assess how antidepressants affect QTc intervals in children. The authors hypothesized that some antidepressants would show an association with QTc prolongation. METHODS: An electronic medical record review was conducted of children aged 5 to 18 years in the Partners Healthcare system with at least 1 prescription of an antidepressant or methadone between February 1990 and August 2011. The authors extracted lifetime diagnoses and QTc interval of patients who had received an electrocardiogram 14 to 90 days after antidepressant or methadone prescription (N = 297). The mean QTc per medication was calculated as compared with the mean of all QTc measurements across medications. The number of patients taking medications who had QTc values in normal, borderline, abnormal, or high were also calculated. RESULTS: Mean QTc values for all medications were in the normal range. The highest mean QTc was in patients on escitalopram (436 milliseconds). The mean QTc for sertraline (416 milliseconds) was significantly lower than all other drugs measured (t(331) = -2.21, p < .05). After controlling for confounding effects, none of the differences in mean QTc compared with other study drugs reached statistical significance. The greatest percentages of abnormal and high QTc values were found among patients taking paroxetine (18.8%), followed by escitalopram (15.4%). None of the children had documented ventricular arrhythmia. CONCLUSION: The results suggest that most antidepressants are not associated with prolonged QTc at doses typically prescribed for children. PMID- 26154714 TI - Evaluating the Statistical Properties of the Pain Interference Index in Children and Adolescents with Chronic Pain. AB - The high prevalence of chronic debilitating pain in pediatric populations calls for more knowledge regarding the impact of pain on functioning or pain interference. This in turn requires valid and reliable instruments to adequately assess the impact of pain on functioning. Also, adequate measures of pain interference are important in evaluations of behavioral interventions aimed at improving functioning. OBJECTIVE: The objectives of this study were to evaluate the statistical properties of the Pain Interference Index (PII), including the factor structure, internal consistency, and concurrent criteria validity of the instrument. METHOD: Data were collected from a consecutive sample of children and adolescents referred to a tertiary pain clinic due to chronic pain (n = 163). A principal component analysis was used to investigate the latent factor structure of items. The internal consistency was assessed by Cronbach's alpha. A set of hierarchical regression analyses was conducted to evaluate the ability of instruments to predict levels of depression and functional disability. RESULTS: Analyses indicated the adequacy of a 1-factor solution with a total of 6 items. The intercorrelation between items and the scale's reliability was satisfactory. Furthermore, bivariate correlations and hierarchical regression analyses illustrate the concurrent criteria validity of the instrument. CONCLUSION: Results support the use of PII as an adequate instrument to assess pain interference in children and adolescents with chronic pain. PMID- 26154715 TI - Beyond Vulnerability: Attachment, Adversity, Gene-Environment Interaction, and Implications for Intervention. PMID- 26154716 TI - Whole Child Care: Coordinating Support to Families. PMID- 26154717 TI - Medically Complex Care: The Newest Competency for Primary Care? AB - CASE: Nola is a complicated 22-month (19-mo corrected) former 34-week premature girl who presents to your practice in the company of her foster caretaker, a maternal aunt. The history you have comes mostly through the lens of her aunt's recall of a variety of clinical encounters and emergency room visits that have taken place at 2 of the region's tertiary care centers, including a prolonged recent hospitalization for failure to thrive. Regrettably, you have no discharge summary on hand from the outside institution.Fortunately, Nola's aunt has come prepared. From her notes, you learn that Nola has a history of feeding difficulties and "global developmental delay." The details of Nola's prenatal and neonatal intensive care unit admission are scant. Nola has been described as having "unusual facial features, such as smallish eyes, low tone, some vision problems." A physical examination demonstrates significant delays in all streams of development. Nola's aunt recalls that she may need a gastrostomy tube pending her weight gain in the next few months.At present, Nola's aunt/foster caretaker is caring for her at home and expresses her concern about 4 major areas: coordinating multiple appointments at various sites, keeping track of involved medical information, getting all of the "paperwork" done to get needed upgrades for a feeding chair, and buying expensive special formula with her own money. Nola's aunt is intelligent and motivated, but she has limited help at home and is overwhelmed with all the aspects of the care. The aunt acknowledges the importance of multiple appointments-feeding support, developmental evaluations, vision, and neurologic assessments. When you inquire who Nola's aunt identifies as her niece's primary care provider, she reports that she has seen different doctors due to the vagaries of her schedule.You conclude that Nola's situation is not likely to improve without a dramatic intervention. As you try to pull together a plan, you wonder what the most effective approach is for the busy clinician. Who should take the lead on a child's care? Can a primary care pediatric clinician partner with other specialists and programs and use other members of a care team effectively? And, does care coordination provide better more cost-effective care? PMID- 26154718 TI - Translations of Developmental Screening Instruments: An Evidence Map of Available Research. AB - OBJECTIVE: Children whose parents do not speak English experience significant disparities in the identification of developmental delays and disorders; however, little is known about the availability and validity of translations of developmental screeners. The goal was to create a map of the scientific evidence regarding translations of the 9 Academy of Pediatrics-recommended screening instruments into languages other than English. METHODS: The authors conducted a systematic search of Medline and PsycINFO, references of identified articles, publishers' Web sites, and official manuals. Through evidence mapping, a new methodology supported by AHRQ and the Cochrane Collaboration, the authors documented the extent and distribution of published evidence supporting translations of developmental screeners. Data extraction focused on 3 steps of the translation and validation process: (1) translation methods used, (2) collection of normative data in the target language, and (3) evidence for reliability and validity. RESULTS: The authors identified 63 distinct translations among the 9 screeners, of which 44 had supporting evidence published in peer-reviewed sources. Of the 63 translations, 35 had at least some published evidence regarding translation methods used, 28 involving normative data, and 32 regarding reliability and/or construct validity. One-third of the translations found were of the Denver Developmental Screening Test. Specific methods used varied greatly across screeners, as did the level of detail with which results were reported. CONCLUSION: Few developmental screeners have been translated into many languages. Evidence map of the authors demonstrates considerable variation in both the amount and the comprehensiveness of information available about translated instruments. Informal guidelines exist for conducting translation of psychometric instruments but not for documentation of this process. The authors propose that uniform guidelines be established for reporting translation research in peer-reviewed journals, similar to those for clinical trials and studies of diagnostic accuracy. PMID- 26154719 TI - [Cp*RhCl2]2: mechanosynthesis and applications in C-H bond functionalisations under ball-milling conditions. AB - A mechanochemical synthesis of [Cp*RhCl2]2 has been developed. Under LAG conditions the organometallic complex can be prepared in a shorter reaction time compared to the standard solution-based protocol. The obtained Rh(iii) dimer is then applicable as catalyst in subsequent solvent-free mechanochemical C-H bond functionalisations of 2-phenylpyridine. PMID- 26154720 TI - Paternally Inherited IGF2 Mutation and Growth Restriction. AB - In humans, mutations in IGF1 or IGF1R cause intrauterine and postnatal growth restriction; however, data on mutations in IGF2, encoding insulin-like growth factor (IGF) II, are lacking. We report an IGF2 variant (c.191C->A, p.Ser64Ter) with evidence of pathogenicity in a multigenerational family with four members who have growth restriction. The phenotype affects only family members who have inherited the variant through paternal transmission, a finding that is consistent with the maternal imprinting status of IGF2. The severe growth restriction in affected family members suggests that IGF-II affects postnatal growth in addition to prenatal growth. Furthermore, the dysmorphic features of affected family members are consistent with a role of deficient IGF-II levels in the cause of the Silver-Russell syndrome. (Funded by Bundesministerium fur Bildung und Forschung and the European Union.). PMID- 26154721 TI - Stimulation of Cellular Proliferation and Migration: Is It a Viable Measure of Photobiomodulation? PMID- 26154722 TI - Effect of Nd:YAG (1064-nm) and Diode Laser (980-nm) EDTA Agitation on Root Dentin Ultrastructure Properties. AB - OBJECTIVE: The purpose of this study was to analyze the effects of agitation of 17% ethylenediaminetetraacetic acid (EDTA) with 1064 nm Nd:YAG and 980 nm diode laser on root dentin microhardness and superficial roughness (with confocal laser scanning microscopy [CLSM]). BACKGROUND DATA: Root canal irrigants are used in an attempt to minimize the negative effects of smear layer. MATERIALS AND METHODS: Twenty-five bovine roots were sectioned longitudinally and divided into five groups (n=10 each): (1) deionized water, (2) 17% EDTA, (3) 17% EDTA with 60 sec manual agitation, (4) 17% EDTA with 50 sec diode laser (2 W) agitation, and (5) 17% EDTA with 50 sec Nd:YAG (1.5 W) laser agitation. Microhardness and superficial roughness values were calculated before and after the procedures at the cervical, middle, and apical root thirds. Microhardness was statistically analyzed using two way ANOVA, paired t test, and Tukey's tests (alpha=0.05). Roughness was statistically analyzed using Kruskal-Wallis, paired t test, and Student-Newman-Keuls tests (alpha=0.05%). RESULTS: Statistically significant differences in microhardness and roughness were observed between the deionized water group and others. EDTA with 1064 nm Nd:YAG or 980 nm diode laser presented the lowest microhardness and the highest roughness values and was significantly different from EDTA with manual agitation and EDTA only (p<0.05). However, there were no differences in microhardness or dentin roughness between the root thirds (p>0.05). CLSM analysis showed that the control samples exhibited smoother surfaces than that of the EDTA groups. CONCLUSIONS: Nd:YAG 1064 nm and 980-nm diode laser EDTA agitation caused greater reduction in microhardness and increased roughness of root dentin than EDTA only or EDTA with manual agitation. PMID- 26154723 TI - The Impact of Low-Level Laser Therapy on Oral Mucositis and Quality of Life in Patients Undergoing Hematopoietic Stem Cell Transplantation Using the Oral Health Impact Profile and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation Questionnaires. AB - OBJECTIVE: The aim of this study was to assess the impact of low-level laser therapy (LLLT) on oral mucositis (OM) and quality of life (QoL) of hematopoietic stem cell transplantation (HSCT) patients. BACKGROUND DATA: OM related to high dose chemotherapy is often associated with increased risk of mortality and impaired QoL in HSCT patients. LLLT has shown promising effects in the prevention and treatment of chemotherapy-induced OM. There is a dearth of literature focused on subjective aspects involving OM and QoL in patients receiving LLLT. METHODS: Thirty-nine patients were randomly assigned to two groups: control (n=19) and laser (n=20). LLLT was performed from the 1st day of the conditioning regimen until day 7 post-HSCT (D+7). OM severity was evaluated in all patients [World Health Organization (WHO) scale]. A blinded observer collected subjective outcomes from patients on admission (AD), D+7 and at discharge (DC). QoL was assessed using the Oral Health Impact Profile (OHIP-14) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaires. Statistical analyses included descriptive, bivariate and multivariate (generalized estimating equation) tests. RESULTS: The overall FACT BMT (p=0.074) and OHIP-14 (p=0.749) scores were not associated with the use of laser therapy. Both instruments showed a deterioration in QoL for the whole sample on D+7. The laser group presented less severe OM than the control group (p<0.001). CONCLUSIONS: LLLT did not influence the oral and general health related QoL of patients undergoing HSCT, although it was clinically effective in reducing the severity of chemotherapy-induced OM. PMID- 26154724 TI - Achieving Dental Analgesia with the Erbium Chromium Yttrium Scandium Gallium Garnet Laser (2780 nm): A Protocol for Painless Conservative Treatment. AB - OBJECTIVE: The aim of this research is to evaluate those techniques and optimal parameters of Erbium Chromium Yttrium Scandium Gallium Garnet (Er,Cr:YSGG) laser use in delivering predictable painless (or with very limited discomfort) restorative cavity preparation without the aid of injected local anesthesia. MATERIAL AND METHODS: This study was conducted on 30 patients (26 adults and 4 youth 9-16 years old; average age, 37) treated in a private practice. For each patient, a single cavity was prepared using the Er,Cr:YSGG laser (2780 nm). An Electric Pulp Tester (EPT) was used to monitor the changes in pulp sensibility threshold. The patient experience was tested before and after the treatment using a modified Visual Analogue Scale (VAS) and Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) to evaluate pain and anxiety. RESULTS: Pain analysis indicated that 80% of patients (24 out of 30) felt no pain and no discomfort, or only a very slight sensation. None of the 30 patients requested anesthesia. EPT was found to be unreliable in evaluating pulpal pain threshold levels. A tendency was noted wherein greater discomfort was felt by anxious patients. On average, the older the patient, the less discomfort was felt. The factors that have a greater tendency to promote discomfort were: posterior teeth, greater caries depth, greater use of higher power levels and ablation time. CONCLUSIONS: Using the Er,Cr:YSGG laser, it was possible to avoid local anesthesia during cavity preparation with a bur. The treatment was effective in a high number of cases (80%), leading to reduction in the anxiety frequently associated with dental care. PMID- 26154725 TI - Evaluation of pH Levels and Surface Roughness After Bleaching and Abrasion Tests of Eight Commercial Products. AB - OBJECTIVE: This in vitro study evaluated the effect of different bleaching protocols and the variation of pH levels of bleaching gels regarding roughness and wear of bovine enamel, after in-office bleaching protocols and brushing. MATERIALS AND METHODS: Ninety fragments were randomly divided into nine groups: C, control; WHP15, 35% hydrogen peroxide (HP) (Whiteness HP, FGM) three gel applications of 15 min each, three sessions with 1 week intervals; WHP45, 35% HP (Whiteness HP) one application/45 min, three sessions with 1 week intervals; LPS, 35% HP (Lase Peroxide, DMC) plus hybrid light (HL) [light-emitting diode (LED)/diode laser], four applications/7 min 30 sec (6 min of HL activation), one session; LPSII, 25% HP (Lase Peroxide II, DMC) plus HL, four applications/7 min 30 sec (6 min of HL activation), one session; LPL, 15% HP (Lase Peroxide Light, DMC) four applications/7 min 30 sec (6 min of HL activation), one session; WO, 35% HP (Whitegold Office, Dentsply) three applications/15 min, three sessions with 1 week intervals; WBC40, 35% HP (Whiteness HP Blue Calcium, FGM) one application/40 min, three sessions with 1 week intervals; and WBC50, 20% HP (Whiteness HP Blue Calcium) one application/50 min, three sessions with 1 week intervals. The median pH values were determined utilizing a pH meter during the initial and final gel applications. A rugosimeter was utilized to evaluate the surface roughness (Ra) before and after bleaching and brushing (100,000 strokes), and the surface wear after brushing. RESULTS: For the results of the pH values, there was a decrease in the pH levels from the initial to the final bleaching time, except for the WBC50. The WO and WBC40 groups exhibited higher pH values. For the results of roughness and wear, there was an increase in surface roughness and wear among the groups. CONCLUSIONS: The pH values tended to decrease from the initial to the final bleaching. After tooth brushing, bleaching procedures with lower pH products provided a significant increase in enamel wear and surface roughness. PMID- 26154726 TI - Effects of Bleaching Agents Combined with Regular and Whitening Toothpastes on Surface Roughness and Mineral Content of Enamel. AB - OBJECTIVE: The purpose of this study was to evaluate surface roughness and changes in the composition of enamel submitted to different bleaching protocols and toothbrushing with regular and whitening toothpastes. BACKGROUND DATA: Bleaching treatment could promote morphological and chemical changes in enamel surface. METHODS: Enamel blocks were randomized into nine groups (n=10) according to the bleaching treatment (no bleaching, control group; 6% hydrogen peroxide, HP; or 10% carbamide peroxide, CP) and toothpaste used (placebo, PL; regular, R; or whitening dentifrice, W). Bleaching was performed according to manufacturers' instructions and all groups were submitted to 30,000 cycles of simulated toothbrushing with toothpaste (PL, R, or W). Mineral content evaluation and enamel roughness were evaluated initially (T1), after bleaching (T2), and after toothbrushing (T3), using an energy-dispersive micro X-ray fluorescence spectrometer and profilometry, respectively. Data were statistically analyzed with two way ANOVA, Tukey, and Dunnett tests (5%). RESULTS: Enamel surface roughness was influenced by bleaching and toothbrushing. Surface roughness increased for the groups that brushed with the placebo dentifrice (CP+PL, HP+PL, C+PL) and for the control group that brushed with whitening dentifrice (C+W). Enamel Ca/P ratio decreased after bleaching, but toothbrushing, regardless of the dentifrice used, did not reduce the enamel mineral content. CONCLUSIONS: The bleaching treatment resulted in a decrease of enamel mineral content, but the studied dentifrices did not contribute to surface mineral loss. PMID- 26154727 TI - Efficacy of Laser Activated Irrigation on Apically Extruded Debris with Different Preparation Systems. AB - OBJECTIVE: The aim of this study was to evaluate apical extrusion of debris in canals prepared with three nickel-titanium (NiTi) rotary file systems [Twisted File Adaptive (TFA), SybronEndo, Orange, CA], Reciproc [(RP), VDW, Munich, Germany], and Revo-S [(RS), MicroMega, Besancon, France] and two irrigation [conventional needle (CNI) and laser-activated (LAI)] techniques. BACKGROUND DATA: Although previous studies have evaluated the amount of apically extruded debris by various instrumentation and irrigation methods, none of them have investigated the effect of LAI during the root canal preparation on debris extrusion. METHODS: Ninety extracted single-rooted human mandibular premolars with straight canals were randomly assigned to six groups (n=15) according to the file and irrigation protocols used: (1) TFA and LAI group, (2) RP and LAI group, (3) RS and LAI group, (4) TFA and CNI group, (5) RP and CNI group, and (6) RS and CNI group. Debris extruded from the apical foramen during root canal preparation was collected into preweighed Eppendorf tubes. The weight of the dry extruded debris was established by subtracting the preinstrumentation and postinstrumentation weight of the Eppendorf tubes for each group. Data were analyzed using the Kruskal Wallis and Mann Whitney U tests with Bonferroni correction to compare groups. RESULTS: LAI groups extruded more debris than CNI groups (p<0.05). However, no statistically significant differences were observed among the file groups when each irrigation method was evaluated separately (p>0.017). CONCLUSIONS: Within the limitations of this study, it can be concluded that the agitation method, such as LAI, had a significant effect on the amount of extrusion. PMID- 26154728 TI - {Ge9[Si(SiMe3)2(SiPh3)]3}(-): Ligand Modification in Metalloid Germanium Cluster Chemistry. AB - The influence of the stabilizing ligand on the physical and chemical properties of a metalloid cluster compound is important for nanotechnology as metalloid clusters are ideal model compounds for metal nanoparticles. Here we present the synthesis of a differently substituted metalloid {Ge9R3}(-) cluster: {Ge9[Si(SiMe3)2(SiPh3)]3}(-) 1, which is obtained in good yield by the reaction of K4Ge9 with ClSi(SiMe3)2(SiPh3). 1 is characterized via NMR and mass spectrometry, but crystallization is hindered. However, the reaction with HgCl2 gives the neutral compound HgGe18[Si(SiMe3)2(SiPh3)]6 2, which can be crystallized and structurally characterized. The presented results are a first step for the investigation of the ligand's influence on the properties of a metalloid germanium cluster compound. PMID- 26154729 TI - The swim force as a body force. AB - Net (as opposed to random) motion of active matter results from an average swim (or propulsive) force. It is shown that the average swim force acts like a body force - an internal body force. As a result, the particle-pressure exerted on a container wall is the sum of the swim pressure [Takatori et al., Phys. Rev. Lett., 2014, 113, 028103] and the 'weight' of the active particles. A continuum description is possible when variations occur on scales larger than the run length of the active particles and gives a Boltzmann-like distribution from a balance of the swim force and the swim pressure. Active particles may also display 'action at a distance' and accumulate adjacent to (or be depleted from) a boundary without any external forces. In the momentum balance for the suspension the mixture of active particles plus fluid - only external body forces appear. PMID- 26154730 TI - Cortisol, testosterone and mood state variation during an official female football competition. AB - BACKGROUND: Endogenous hormones are essential on the control of physiological reactions and adaptations during sport performance. This study aims to compare the mood state and the salivary levels of cortisol and testosterone during an official female association football tournament. METHODS: Twenty female football players (22.85+/-4.2 years) from the Portuguese women's national team were included in the study. Mood, salivary cortisol and testosterone levels were examined in five moments over the championship (M1, neutral measures; M2-M5, on every match day). Saliva samples were collected before breakfast and immediately after each match. Mood was measured by the profile of mood states questionnaire (POMS); hormone levels were measure by immunoassay methods. RESULTS: Iceberg Profiles of POMS were observed during all the moments of evaluation (M2-M5), showing a decrease in vigor and an increase in tension and depression in both team defeats (M2 and M5). There is no relationship between the hormones levels and the outcome of the competition, once cortisol and testosterone decrease from pre-match to post-match in both wins (M2 and M5) and defeats (M3 and M4). For testosterone the observed decrease is significantly different (P<0.05) before and after all matches. CONCLUSIONS: Our results show a pattern in mood states behavior. Cortisol and testosterone decrease after match and throughout the tournament, independently of the match outcome. The absence of hormone fluctuations related to competition performance points out that top-level professional football players training systematically and regularly seem to be very well adapted to competition stress effect. PMID- 26154731 TI - Historical Manifestations! PMID- 26154732 TI - Telemedicine Accolades for Rashid L. Bashshur. PMID- 26154733 TI - Evaluation of the prevalence of and factors associated with laryngeal diseases among the general population. AB - OBJECTIVES/HYPOTHESIS: Despite the high prevalence of voice disorders, the prevalence of laryngeal disease in the general population has not been determined using laryngoscopy. Factors considered associated with laryngeal disease have mostly been assessed using patient data or highly specific populations. We evaluated the prevalence of and associated factors with laryngeal diseases in the general Korean population. STUDY DESIGN: Cross-sectional study. METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey for 19,039 participants assessed between 2008 and 2011. The prevalence, subjective discomforts rates of, and odd ratios (demographics, life-style factors, and diseases factors) for laryngeal disease were analyzed using simple and multiple logistic regression analyses, taking into account the complex sampling structure of the data. RESULTS: The top five laryngeal diseases in prevalence were laryngitis (3,513/100,000), vocal nodules (1,487/100,000), vocal polyp (404/100,000), Reinke's edema (347/100,000), and epiglottic cyst (296/100,000). Prevalence of laryngeal disease was higher in males, whereas the rate of subjective voice complaints was higher in females. In the logistic regression analysis, gender was not associated with laryngeal diseases after adjusting for other factors. We observed a positive association between low body mass index (BMI) and vocal nodules, and between high BMI and laryngitis, smoking and epiglottic cyst/hyperkeratosis/laryngeal cancer, higher education level and vocal nodules, and allergic rhinitis and vocal nodules/laryngitis/epiglottic cyst. CONCLUSIONS: The rate of subjective voice complaints and laryngeal disease co occurrence was low. This study provides more reliable information of laryngeal disease because it includes participants without subjective complaints. LEVEL OF EVIDENCE: 2b. PMID- 26154735 TI - The Protective Effects of the VEGF -2578C>A and -1154G>A Polymorphisms Against Hypertension Susceptibility. AB - AIMS: It has been reported that plasma vascular endothelial growth factor (VEGF) levels are elevated in hypertensive patients. The aim of this study was to investigate the association of -2578C>A and -1154G>A polymorphisms in the VEGF gene with susceptibility to hypertension. METHODS: A total of 640 subjects (320 hypertensive patients and 320 healthy normotensive subjects) were enrolled in the study. Genotyping of the -2578C>A and -1154G>A polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: The CA and AA genotypes and dominant and recessive models of the 2578C>A polymorphism were protective against MetS susceptibility (p<0.0001, p=0.001, p<0.0001, and p=0.015, respectively). The GA genotype and dominant model (GG vs. GA+AA) of the -1154G >A polymorphism were found less frequently in patients with hypertension compared to the controls (p=0.0001, p<0.0001, respectively). Haplotypes of the -2578C>A and -1154G>A polymorphisms were also different between the patients and controls. CONCLUSIONS: The A allele of the 2578C>A polymorphism and haplotypes of the -2578C>A and -1154G>A polymorphisms in the promoter region of the VEGF gene might be protective against the development of hypertension in Koreans. Further studies examining these associations in other populations are warranted. PMID- 26154734 TI - Plasma viraemia in HIV-positive pregnant women entering antenatal care in South Africa. AB - INTRODUCTION: Plasma HIV viral load (VL) is the principle determinant of mother to-child HIV transmission (MTCT), yet there are few data on VL in populations of pregnant women in sub-Saharan Africa. We examined the distribution and determinants of VL in HIV-positive women seeking antenatal care (ANC) in Cape Town, South Africa. METHODS: Consecutive HIV-positive pregnant women making their first antenatal clinic visit were recruited into a cross-sectional study of viraemia in pregnancy, including a brief questionnaire and specimens for VL testing and CD4 cell enumeration. RESULTS & DISCUSSION: Overall 5551 pregnant women sought ANC during the study period, of whom 1839 (33%) were HIV positive and 1521 (85%) were included. Approximately two-thirds of HIV-positive women in the sample (n=947) were not on antiretrovirals at the time of the first ANC visit, and the remainder (38%, n=574) had initiated antiretroviral therapy (ART) prior to conception. For women not on ART, the median VL was 3.98 log10 copies/mL; in this group, the sensitivity of CD4 cell counts <=350 cells/uL in detecting VL>10,000 copies/mL was 64% and this increased to 78% with a CD4 threshold of <=500 cells/uL. Among women on ART, 78% had VL<50 copies/mL and 13% had VL >1000 copies/mL at the time of their ANC visit. CONCLUSIONS: VL >10,000 copies/mL was commonly observed in women not on ART with CD4 cell counts >350 cells/uL, suggesting that CD4 cell counts may not be adequately sensitive in identifying women at greatest risk of MTCT. A large proportion of women entering ANC initiated ART before conception, and in this group more than 10% had VL>1000 copies/mL despite ART use. VL monitoring during pregnancy may help to identify pregnancies that require additional clinical attention to minimize MTCT risk and improve maternal and child health outcomes. PMID- 26154736 TI - Posterior Subtenon's Capsule Triamcinolone Acetonide Injection for the Treatment of Diabetic Macular Edema. AB - PURPOSE: To evaluate and compare the efficacy of posterior subtenon's triamcinolone injections versus grid laser photocoagulation (GLP) combined with posterior subtenon's triamcinolone injection in eyes with diabetic macular edema (DME). METHODS: In this prospective clinical study, 42 eyes with DME that showed a decrease in visual acuity (VA) were included. The first group consisted of 22 eyes that received a posterior subtenon's injection of 40 mg of triamcinolone acetonide under topical anesthesia. The second group of 20 eyes received macular GLP applied 1 month after subtenon's triamcinolone acetonide (STTA) injection. All patients were evaluated at baseline and 1 day; 1, 2, 4, 6, and 8 weeks; and 3 and 6 months after injection. In some patients, injections were repeated after 3 months. The main outcome measures were VA, central macular thickness (CMT), intraocular pressure, cataract progression, and frequency of complications. RESULTS: The mean baseline CMT for Group I was 456.85 +/- 56.90 MUm. The mean baseline CMT for Group II was 455.66 +/- 57 MUm. In the first group, mean CMTs for second week, 8th week, 12th week, and 6th month were 258.15, 276.50, 280.05, and 433.30 MUm, respectively. In the second group, mean CMTs for second week, 8th week, 12th week, and 6th month were 261.42, 272.76, 284.71, and 291.76 MUm, respectively. Before treatment, in the first group, the mean best-corrected visual acuity (BCVA) measured using a Snellen chart was 0.19, while the first week, third, and sixth month BCVA means were 0.59, 0.57, and 0.41, respectively. Before treatment, BCVA in the second group was 0.17, while the first week, third, and sixth month means were 0.61, 0.64, and 0.60, respectively. Treatment complications included cataracts in 4 eyes and glaucoma in 1 eye. CONCLUSION: There is a temporary therapeutic effect of posterior subtenon's triamcinolone injection without laser photocoagulation. GLP improves VA and reduces the risk of recurrent macular edema after posterior STTA injection. PMID- 26154738 TI - 3D assembly of silica encapsulated semiconductor nanocrystals. AB - Non-ordered porous networks, so-called aerogels, can be achieved by the 3D assembly of quantum dots (QDs). These materials are well suited for photonic applications, however a certain quenching of the photoluminescence (PL) intensity is observed in these structures. This PL quenching is mainly attributed to the energy transfer mechanisms that result from the close contact of the nanoparticles in the network. Here, we demonstrate the formation of a novel aerogel material with non-quenching PL behaviour by non-classical, reversible gel formation from tetrazole capped silica encapsulated QDs. Monitoring of the gelation/degelation by optical spectroscopy showed that the optical properties of the nanocrystals could be preserved in the 3D network since no spectral shifts and lifetime shortening, which can be attributed to the coupling between QDs, are observed in the gels as compared to the original colloidal solutions. In comparison with other QD-silica monoliths, QDs in our gels are homogeneously distributed with a distinct and controllable distance. In addition we show that the silica shell is porous and allows metal ions to pass through the shell and interact with the QD core causing detectable changes of the emission properties. We further show the applicability of this gelation method to other QD materials which sets the stage for facile preparation of a variety of mixed gel structures. PMID- 26154737 TI - Noninvasive In-Vivo Quantification of Mechanical Heterogeneity of Invasive Breast Carcinomas. AB - Heterogeneity is a hallmark of cancer whether one considers the genotype of cancerous cells, the composition of their microenvironment, the distribution of blood and lymphatic microvasculature, or the spatial distribution of the desmoplastic reaction. It is logical to expect that this heterogeneity in tumor microenvironment will lead to spatial heterogeneity in its mechanical properties. In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging. By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors. Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous. PMID- 26154739 TI - Systematic Perturbations of Binuclear Non-heme Iron Sites: Structure and Dioxygen Reactivity of de Novo Due Ferri Proteins. AB - DFsc (single-chain due ferri) proteins allow for modeling binuclear non-heme iron enzymes with a similar fold. Three 4A -> 4G variants of DFsc were studied to investigate the effects of (1) increasing the size of the substrate/solvent access channel (G4DFsc), (2) including an additional His residue in the first coordination sphere along with three additional helix-stabilizing mutations [3His G4DFsc(Mut3)], and (3) the three helix-stabilizing mutations alone [G4DFsc(Mut3)] on the biferrous structures and their O2 reactivities. Near-infrared circular dichroism and magnetic circular dichroism (MCD) spectroscopy show that the 4A -> 4G mutations increase coordination of the diiron site from 4-coordinate/5 coordinate to 5-coordinate/5-coordinate, likely reflecting increased solvent accessibility. While the three helix-stabilizing mutations [G4DFsc(Mut3)] do not affect the coordination number, addition of the third active site His residue [3His-G4DFsc(Mut3)] results in a 5-coordinate/6-coordinate site. Although all 4A > 4G variants have significantly slower pseudo-first-order rates when reacting with excess O2 than DFsc (~2 s(-1)), G4DFsc and 3His-G4DFsc(Mut3) have rates (~0.02 and ~0.04 s(-1)) faster than that of G4DFsc(Mut3) (~0.002 s(-1)). These trends in the rate of O2 reactivity correlate with exchange coupling between the Fe(II) sites and suggest that the two-electron reduction of O2 occurs through end on binding at one Fe(II) rather than through a peroxy-bridged intermediate. UV vis absorption and MCD spectroscopies indicate that an Fe(III)Fe(III)-OH species first forms in all three variants but converts into an Fe(III)-MU-OH-Fe(III) species only in the 2-His forms, a process inhibited by the additional active site His ligand that coordinatively saturates one of the iron centers in 3His G4DFsc(Mut3). PMID- 26154740 TI - Orthogonal sampling in free-energy calculations of residue mutations in a tripeptide: TI versus lambda-LEUS. AB - In a recent article (Bieler et al., J. Chem. Theory Comput. 2014, 10, 3006), we introduced a combination of lambda-dynamics and local-elevation umbrella-sampling termed lambda-LEUS to calculate free-energy changes associated with alchemical processes using molecular dynamics simulations. This method was suggested to be more efficient than thermodynamic integration (TI), because the dynamical variation of the alchemical variable lambda opens up pathways to circumvent barriers in the orthogonal space (defined by the N - 1 degrees of freedom that are not subjected to the sampling enhancement), a feature lambda-LEUS shares with Hamiltonian replica-exchange (HR) approaches. However, the mutation considered, hydroquinone to benzene in water, was no real challenge in terms of orthogonal space properties, which were restricted to solvent-relaxation processes. In the present article, we revisit the comparison between TI and lambda-LEUS considering non-trivial mutations of the central residue X of a KXK tripeptide in water (with X = G, E, K, S, F, or Y). Side-chain interactions that may include salt bridges, hydrogen bonds or steric clashes lead to slow relaxation in the orthogonal space, mainly in the two-dimensional subspace spanned by the central phi and psi dihedral angles of the peptide. The efficiency enhancement afforded by lambda LEUS is confirmed in this more complex test system and can be attributed explicitly to the improved sampling of the orthogonal space. The sensitivity of the results to the nontrivial choices of a mass parameter and of a thermostat coupling time for the alchemical variable is also investigated, resulting in recommended ranges of 50 to 100 u nm(2) and 0.2 to 0.5 ps, respectively. PMID- 26154741 TI - Prevalence and Mechanisms of Dynamic Chemical Defenses in Tropical Sponges. AB - Sponges and other sessile invertebrates are lacking behavioural escape or defense mechanisms and rely therefore on morphological or chemical defenses. Studies from terrestrial systems and marine algae demonstrated facultative defenses like induction and activation to be common, suggesting that sessile marine organisms also evolved mechanisms to increase the efficiency of their chemical defense. However, inducible defenses in sponges have not been investigated so far and studies on activated defenses are rare. We investigated whether tropical sponge species induce defenses in response to artificial predation and whether wounding triggers defense activation. Additionally, we tested if these mechanisms are also used to boost antimicrobial activity to avoid bacterial infection. Laboratory experiments with eight pacific sponge species showed that 87% of the tested species were chemically defended. Two species, Stylissa massa and Melophlus sarasinorum, induced defenses in response to simulated predation, which is the first demonstration of induced antipredatory defenses in marine sponges. One species, M. sarasinorum, also showed activated defense in response to wounding. Interestingly, 50% of the tested sponge species demonstrated induced antimicrobial defense. Simulated predation increased the antimicrobial defenses in Aplysinella sp., Cacospongia sp., M. sarasinorum, and S. massa. Our results suggest that wounding selects for induced antimicrobial defenses to protect sponges from pathogens that could otherwise invade the sponge tissue via feeding scars. PMID- 26154742 TI - Influence of breeding site availability on the oviposition behaviour of Aedes aegypti. AB - Despite the importance of the mosquito Aedes aegypti in the transmission of arboviruses, such as yellow fever, Chikungunya fever and dengue fever, some aspects of their behaviour remain unknown. In the present study, the oviposition behaviour of Ae. aegypti females that were exposed to different densities of breeding sites (2, 4, 8 and 16) was evaluated in laboratory and semi-field conditions. The number of breeding sites that were used was proportional to the number available, but tended towards stabilisation. Females used four-six breeding sites on average, with a maximum of 11. A high percentage of eggs was observed in the water, along with the presence of a breeding site termed "favourite", which received at least 40% of the eggs. The results are discussed in ecological, evolutionary and epidemiological approaches. PMID- 26154743 TI - Molecular profiling of drug resistant isolates of Mycobacterium tuberculosis in the state of Santa Catarina, southern Brazil. AB - Drug resistance is a global threat and one of the main contributing factors to tuberculosis (TB) outbreaks. The goal of this study was to analyse the molecular profile of multidrug-resistant TB (MDR-TB) in the state of Santa Catarina in southern Brazil. Fifty-three MDR Mycobacterium tuberculosis clinical isolates were analysed by spoligotyping and a partial region of the rpoB gene, which is associated with rifampicin resistance (RMP-R), was sequenced. Some isolates were also distinguished by their mycobacterial interspersed repetitive units (MIRU). S531L was the most prevalent mutation found within rpoB in RMP-R isolates (58.5%), followed by S531W (20.8%). Only two MDR isolates showed no mutations within rpoB. Isolates of the Latin American Mediterranean (LAM) family were the most prevalent (45.3%) found by spoligotyping, followed by Haarlem (9.4%) and T (7.5%) families. SIT106 was found in 26.4% of isolates and all SIT106 isolates typed by MIRU-12 (5 out of 14) belong to MIT251. There was a high correlation between the S531W mutation and the LAM family mainly because all SIT2263 (LAM9) isolates carry this mutation. Among isolates with the S531W mutation in rpoB MIRU demonstrates a cluster formed by four isolates (SIT2263 and MIT163) and very similar profiles were observed between eight of the nine isolates. Better characterisation of TB isolates may lead to new ways in which to control and treat TB in this region of Brazil. PMID- 26154745 TI - Using remote ischemic conditioning to reduce acute kidney injury in patients undergoing percutaneous coronary intervention: a meta-analysis. AB - BACKGROUND AND AIMS: It remains uncertain whether remote ischemic conditioning (RIC) could prevent acute kidney injury (AKI) in patients undergoing percutaneous coronary intervention (PCI). Thus, this meta-analysis aiming to explore the renoprotective role of RIC in patients undergoing PCI was carried out. METHODS: PubMed, Web of Science, and Cochrane Library were searched from inception to 31 December 2014 to identify eligible randomized controlled trials. Pooled risk ratio, mean, standard deviation and 95% CI were used to assess the effect by fixed- or random-effect models. Heterogeneity was assessed by the Cochran Q and I( 2) statistics. RESULTS: Nine trials were included in this study. RIC decreased the AKI incidence in patients undergoing PCI compared with control individuals (P < 0.001; RR, 0.53; 95% CI, 0.39-0.71; P for heterogeneity = 0.15; heterogeneity chi(2 )= 13.38; I(2 )= 33%). Besides, limb conditioning attenuated AKI (P = 0.001; RR, 0.57; 95% CI, 0.41-0.81; P for heterogeneity = 0.13; heterogeneity chi(2 )= 12.48; I(2 )= 36%). Remote postconditioning may reduce the AKI incidence (P = 0.03; RR, 0.65; 95% CI, 0.44-0.97; P for heterogeneity = 0.15; heterogeneity chi(2 )= 5.36; I(2 )= 44%); remote preconditioning could also play a renoprotective role (P < 0.001; RR, 0.42; 95% CI, 0.27-0.65; P for heterogeneity = 0.31; heterogeneity chi(2 )= 5.98; I(2 )= 16%). CONCLUSIONS: RIC may not only confer cardioprotection, but also reduce the incidence of AKI in patients undergoing PCI, ultimately leading to better clinical outcomes. RIC may potentially be a powerful approach conferring protection in patients undergoing PCI in future clinical practice. More large-scale trials are required to obtain a more reliable conclusion. PMID- 26154744 TI - Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C. AB - Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women. PMID- 26154746 TI - [Prediction of growth from an early age: curve matching with the TNO Growth Predictor]. AB - Curve matching is a new big data technique to predict an outcome given earlier measurements. Here we apply curve matching to predict the future growth of a specific child, the target child. The method searches in large datasets of longitudinal growth data for other children who are similar to the target child in terms of factors that influence growth. The observed growth curves of these matched children provide valuable insights into the future growth of the target child. The TNO Groeivoorspeller (TNO Growth Predictor) plots the expected growth of the target child, as well as the uncertainty of the prediction. Curve matching is a general technique that can also be used for other health measures. The key requirement is the availability of relevant longitudinal data on the outcome and its determinants. PMID- 26154747 TI - [A woman with swollen lips]. AB - A 23-year-old Caucasian female came to the emergency room with thick and painful lips after using ecstasy the night before. She had been biting her lips all night long. This caused a contusion of her lips, which was accompanied by oedema. PMID- 26154748 TI - [Diagnostic tests in GP out-of-hours services in the Netherlands]. AB - OBJECTIVE: To determine GPs' access to diagnostic tests (medical imaging, laboratory tests, and point-of-care tests) during GP out-of-hours care in the Netherlands and to assess whether access differs between services located adjacent to or separate from an Accident and Emergency (A&E) department. DESIGN: Cross-sectional survey. METHOD: In 2014 we invited all GP out-of-hours services in the Netherlands to participate in a survey on GPs' access to diagnostic tests in Dutch GP out-of-hours services. RESULTS: 117 GP out-of-hours services participated in the survey; response rate 100%. Although access to diagnostic tests during GP out-of-hours care varied across services, overall there was limited access. Electrocardiography was available in 26% (30/117) of all services, and conventional radiography in 19% (22/117). Access to various types of laboratory tests ranged between 37% (43/117) and 65% (76/117). All services had glucose point-of-care tests and urine dipstick tests available. We observed no relevant differences in access to in-house diagnostic tests between services adjacent to or separate from an A&E department. More than half (56%) of out-of hours services expressed plans to expand their diagnostic facilities. CONCLUSION: GPs in the Netherlands have limited and varying access to diagnostic tests in GP out-of-hours services. GPs working in out-of-hours services adjacent to A&E departments do not have wider access to diagnostic tests than GPs working at a separate location. With current developments towards joint organisation structures of GP out-of-hours services and A&E departments in the Netherlands, the organisation of diagnostic facilities within out-of-hours care may be subject of debate. PMID- 26154749 TI - [A female patient with an unusual swelling in the groin]. AB - A swelling in the groin is a highly prevalent complaint. However, surgical exploration can sometimes reveal an unexpected finding, such as in our case of a postmenopausal 52-year-old female patient. After surgical excision, a left groin mass appeared to be a leiomyoma of the round ligament of the uterus. PMID- 26154750 TI - [Limitations to medical treatment; discussing treatment limitation, and stubbornness in practice]. AB - Many courses for caregivers are aimed at teaching them to commence medical treatment as soon as possible in an acute situation. However, this treatment may not always be in line with the patient's wishes. In this article we describe three patients who received treatment despite their wish not to be treated. More attention should be given to talking to patients about their advanced directives; we suggest how these discussions can be initiated in the daily care of our patients. PMID- 26154751 TI - [Another indicator of correlation between cholesterol and type 2 diabetes mellitus]. AB - Recently a Dutch research group published an analysis of the Dutch screening programme for familial hypercholesterolemia (FH) in JAMA. They showed that the prevalence of type 2 diabetes mellitus (DM2) was lower among persons with a mutation causing FH than in their unaffected relatives. FH patients who were carriers of mutations without residual LDL receptor function had DM2 less often than those with residual LDL receptor function. Although it is tempting to speculate about a causal relationship between cholesterol transport and DM2, another explanation could be the healthier lifestyle of patients with FH. This study should not change clinical practice and should certainly not lead to discontinuation of statin therapy. PMID- 26154753 TI - Incidence, prevalence, and medical expenditures of classical amyotrophic lateral sclerosis in Taiwan, 1999-2008. AB - BACKGROUND/PURPOSE: Amyotrophic lateral sclerosis (ALS) is a rare disease, which makes the estimation of incidence and prevalence difficult in Taiwan. This study was conducted to investigate the incidence, prevalence, and medical expenditure of ALS in Taiwan. METHODS: Patients who had at least one service claim either as an outpatient or inpatient between the years 2004 and 2007 and were over 15 years of age with a primary diagnosis of ALS were identified from the National Health Insurance Research Database. Additionally, ALS patients with serious disability database certificates over 15 years of age were included for the calculation of incidence and prevalence between the years 1999 and 2008. Lastly, the total medical expenditure, including ventilator use and riluzole, were reported. RESULTS: In 2006 and 2008, the average annual incidence and prevalence of ALS was 0.51 and 1.97 (per 10(5)), respectively, in Taiwan. The male-to-female ratio of incidence for ALS was 1.67. The average medical expenditure for ALS patients stayed steady at 16-fold greater than the general population of Taiwan in 2008. The percentage of ventilator and riluzole expenditure as a proportion of total medical expense decreased from 55% in 2000 to 33% in 2008. CONCLUSION: The incidence and average medical expenditure of ALS patients remained stable over the years in Taiwan, however, as a proportion of total medical expenses, expenditure on ventilator and riluzole decreased over the study period. PMID- 26154752 TI - A Tissue-Engineered Chondrocyte Cell Sheet Induces Extracellular Matrix Modification to Enhance Ventricular Biomechanics and Attenuate Myocardial Stiffness in Ischemic Cardiomyopathy. AB - There exists a substantial body of work describing cardiac support devices to mechanically support the left ventricle (LV); however, these devices lack biological effects. To remedy this, we implemented a cell sheet engineering approach utilizing chondrocytes, which in their natural environment produce a relatively elastic extracellular matrix (ECM) for a cushioning effect. Therefore, we hypothesized that a chondrocyte cell sheet applied to infarcted and borderzone myocardium will biologically enhance the ventricular ECM and increase elasticity to augment cardiac function in a model of ischemic cardiomyopathy (ICM). Primary articular cartilage chondrocytes of Wistar rats were isolated and cultured on temperature-responsive culture dishes to generate cell sheets. A rodent ICM model was created by ligating the left anterior descending coronary artery. Rats were divided into two groups: cell sheet transplantation (1.0 * 10(7) cells/dish) and no treatment. The cell sheet was placed onto the surface of the heart covering the infarct and borderzone areas. At 4 weeks following treatment, the decreased fibrotic extension and increased elastic microfiber networks in the infarct and borderzone areas correlated with this technology's potential to stimulate ECM formation. The enhanced ventricular elasticity was further confirmed by the axial stretch test, which revealed that the cell sheet tended to attenuate tensile modulus, a parameter of stiffness. This translated to increased wall thickness in the infarct area, decreased LV volume, wall stress, mass, and improvement of LV function. Thus, the chondrocyte cell sheet strengthens the ventricular biomechanical properties by inducing the formation of elastic microfiber networks in ICM, resulting in attenuated myocardial stiffness and improved myocardial function. PMID- 26154754 TI - Unique clinical characteristics and SCN5A mutations in patients with Brugada syndrome in Taiwan. AB - BACKGROUND/PURPOSE: Brugada syndrome (BrS) is a hereditable sudden cardiac death (SCD). Mutations in the SCN5A gene (the most common BrS-causing gene) are responsible for 20-25% of this disease in Caucasian populations. However, the prevalence of SCN5A mutations in patients with BrS in the Chinese Han population in Taiwan remains unknown. Therefore, in this study, we investigated the prevalence of the SCN5A mutation in the largest BrS cohort in Taiwan. METHODS: We consecutively enrolled 47 unrelated patients with BrS from medical centers and hospitals in Taiwan between 2000 and 2010. Mutations within all the 27 translated exons, and exon-intron boundaries of the SCN5A-encoded cardiac sodium channel were screened in all patients with BrS using direct sequencing. A total of 500 unrelated healthy volunteers with a normal electrocardiogram were genotyped as a control group. RESULTS: SCN5A genetic variants were identified in 14 of the 47 patients with BrS and four of the 14 patients with BrS had missense mutations (1651 G>A, 1776 C>G, 3578 G>A). The prevalence rate of SCN5A mutations was approximately 8% (4/47), which was significantly lower than that reported in Caucasian populations (20-25%; p = 0.0007). The average age of these 14 BrS patients with SCN5A variants at diagnosis (12 men and 2 women) was 40 +/- 13 years. Four patients experienced SCD, and six presented with seizure or syncope. Only three patients (3/14, 21.4%) had a family history of SCD. CONCLUSION: The prevalence of SCN5A mutations in the Chinese Han population in Taiwan may be lower than that reported in the Caucasian populations. In addition, most patients with BrS did not have a family history of SCD. PMID- 26154755 TI - Sequence variants of the aging gene CISD2 and the risk for Alzheimer's disease. AB - BACKGROUND/PURPOSE: The CISD2 gene has been related to life span control and mitochondrial dysfunction in animals. In addition, inhibition of mitochondrial enzymes due to an accumulation of beta-amyloid peptide has been related to Alzheimer's disease (AD). This study aimed to explore the association between sequence variants of the CISD2 gene and risk for AD, which has not been explored previously. METHODS: This was a case-control study involving a total of 276 patients with AD who were recruited from three teaching hospitals in Taiwan from 2007 to 2010; 460 controls were recruited from elderly individuals attending for health check-ups and volunteers in the hospital during the same period of time. All participants were aged 60 years or older. Two haplotype-tagging single nucleotide polymorphisms (htSNPs), rs223330 and rs223331, were selected from the CISD2 gene to test the association between their polymorphisms and the risk for dementia, and how ApoE E4 status, sex, hypertension, and type 2 diabetes mellitus might modify this association. RESULTS: rs223330 variant carriage was not associated with risk for AD [TT versus CC: adjusted odds ratio (AOR) = 0.98, 95% confidence interval (CI) = 0.59-1.62; TC versus CC: AOR = 0.72, 95% CI = 0.47 1.11]. Similar findings were observed for rs223331 (AA versus TT: AOR = 1.12; AT versus TT: AOR = 0.99). In addition, hypertension significantly modified the association between rs223331 and risk for AD (p = 0.005).Three common haplotypes (with a frequency of 99.8%) were observed for CISD2. Common CISD2 haplotypes were not associated with the risk for AD. CONCLUSION: Our findings suggested that CISD2 htSNPs are not associated with AD risk. PMID- 26154756 TI - Adult idiopathic hypertrophic pyloric stenosis. AB - Idiopathic hypertrophic pyloric stenosis (IHPS) is a predominantly infantile disease. The adult type of IHPS is extremely rare but it has been well recognized since the 19(th) century. We report a case of a 47-year-old male patient who presented with postprandial nausea and vomiting. He underwent upper gastrointestinal endoscopy, and gastric outlet obstruction was discovered. The upper gastrointestinal barium study showed a distended stomach with delayed gastric emptying due to pyloric stenosis. The abdominal computed tomography revealed thickening of the distal stomach. Since gastric malignancy could not be excluded, he underwent antrectomy with Billroth I anastomosis. The pathology revealed no malignancy but showed hypertrophy and hyperplasia of the inner circular muscle of the pylorus, which was compatible with IHPS. We reported the case to remind young physicians of this rare disease. PMID- 26154757 TI - Treatment of young children with CNS-positive acute lymphoblastic leukemia without cranial radiotherapy. AB - BACKGROUND: Due to the long-term sequelae of cranial radiotherapy (CRT), contemporary treatment protocols for children with acute lymphoblastic leukemia (ALL) aim to limit the use of prophylactic CRT. For patients with central nervous system (CNS) involvement with ALL at diagnosis, the use of CRT remains common. Children <5 years of age are a particularly challenging subgroup in whom the consequences of CRT can be devastating. PROCEDURE: This study retrospectively describes the overall (OS) and event-free survival (EFS) of young children (1-5 years) who were treated for CNS-positive ALL at the Hospital for Sick Children between 2000 and 2013. RESULTS: Of a total of 19 patients, two were treated with upfront CRT, both as part of the conditioning regimen prior to HSCT. All patients received intensification of CNS-directed chemotherapy by triple intra-thecal chemotherapy (84.2%), use of dexamethasone in induction (57.9%) and maintenance (66.7%), and high-dose methotrexate (77.8%). The OS was 84.2 +/- 8.4% and EFS was 79.0 +/- 9.4% with a median follow-up time of 4.3 years (range, 2.6-8.2). The cumulative incidence of CNS relapse was 5.2 +/- 5.1%. CONCLUSIONS: We conclude that omission of CRT from the treatment of young children with ALL involving the CNS is associated with acceptable survival and avoids potentially devastating late effects in this group. PMID- 26154758 TI - A child with cerebral palsy: what difference does it make for parents? PMID- 26154759 TI - Which Species Are We Researching and Why? A Case Study of the Ecology of British Breeding Birds. AB - Our ecological knowledge base is extensive, but the motivations for research are many and varied, leading to unequal species representation and coverage. As this evidence is used to support a wide range of conservation, management and policy actions, it is important that gaps and biases are identified and understood. In this paper we detail a method for quantifying research effort and impact at the individual species level, and go on to investigate the factors that best explain between-species differences in outputs. We do this using British breeding birds as a case study, producing a ranked list of species based on two scientific publication metrics: total number of papers (a measure of research quantity) and h-index (a measure of the number of highly cited papers on a topic--an indication of research quality). Widespread, populous species which are native, resident and in receipt of biodiversity action plans produced significantly higher publication metrics. Guild was also significant, birds of prey the most studied group, with pigeons and doves the least studied. The model outputs for both metrics were very similar, suggesting that, at least in this example, research quantity and quality were highly correlated. The results highlight three key gaps in the evidence base, with fewer citations and publications relating to migrant breeders, introduced species and species which have experienced contractions in distribution. We suggest that the use of publication metrics in this way provides a novel approach to understanding the scale and drivers of both research quantity and impact at a species level and could be widely applied, both taxonomically and geographically. PMID- 26154760 TI - Controlling CH3NH3PbI(3-x)Cl(x) Film Morphology with Two-Step Annealing Method for Efficient Hybrid Perovskite Solar Cells. AB - The methylammonium lead halide perovskite solar cells have become very attractive because they can be prepared with low-cost solution-processable technology and their power conversion efficiency have been increasing from 3.9% to 20% in recent years. However, the high performance of perovskite photovoltaic devices are dependent on the complicated process to prepare compact perovskite films with large grain size. Herein, a new method is developed to achieve excellent CH3NH3PbI3-xClx film with fine morphology and crystallization based on one step deposition and two-step annealing process. This method include the spin coating deposition of the perovskite films with the precursor solution of PbI2, PbCl2, and CH3NH3I at the molar ratio 1:1:4 in dimethylformamide (DMF) and the post two step annealing (TSA). The first annealing is achieved by solvent-induced process in DMF to promote migration and interdiffusion of the solvent-assisted precursor ions and molecules and realize large size grain growth. The second annealing is conducted by thermal-induced process to further improve morphology and crystallization of films. The compact perovskite films are successfully prepared with grain size up to 1.1 MUm according to SEM observation. The PL decay lifetime, and the optic energy gap for the film with two-step annealing are 460 ns and 1.575 eV, respectively, while they are 307 and 327 ns and 1.577 and 1.582 eV for the films annealed in one-step thermal and one-step solvent process. On the basis of the TSA process, the photovoltaic devices exhibit the best efficiency of 14% under AM 1.5G irradiation (100 mW.cm(-2)). PMID- 26154761 TI - The Golden Section as Optical Limitation. AB - The golden section, phi = (1 + ?5)/2 = 1.618... and its companion phi = 1/phi = phi -1 = 0.618..., are irrational numbers which for centuries were believed to confer aesthetic appeal. In line with the presence of golden sectioning in natural growth patterns, recent EEG recordings show an absence of coherence between brain frequencies related by the golden ratio, suggesting the potential relevance of the golden section to brain dynamics. Using Mondrian-type patterns comprising a number of paired sections in a range of five section-section areal ratios (including golden-sectioned pairs), participants were asked to indicate as rapidly and accurately as possible the polarity (light or dark) of the smallest section in the patterns. They were also asked to independently assess the aesthetic appeal of the patterns. No preference was found for golden-sectioned patterns, while reaction times (RTs) tended to decrease overall with increasing ratio independently of each pattern's fractal dimensionality. (Fractal dimensionality was unrelated to ratio and measured in terms of the Minkowski Bouligand box-counting dimension). The ease of detecting the smallest section also decreased with increasing ratio, although RTs were found to be substantially slower for golden-sectioned patterns under 8-paired sectioned conditions. This was confirmed by a significant linear relationship between RT and ratio (p < .001) only when the golden-sectioned RTs were excluded [the relationship was non significant for the full complement of ratios (p = .217)]. Image analysis revealed an absence of spatial frequencies between 4 and 8 cycles-per-degree that was exclusive to the 8-paired (golden)-sectioned patterns. The significance of this was demonstrated in a subsequent experiment by addition of uniformly distributed random noise to the patterns. This provided a uniform spatial frequency profile for all patterns, which did not influence the decrease in RT with increasing ratio but abolished the elevated RTs to golden-sectioned patterns. This suggests that optical limitation in the form of reduced inter neural synchronization during spatial-frequency coding may be the foundation for the perceptual effects of golden sectioning. PMID- 26154762 TI - Switching of the Laryngeal Cavity From the Respiratory Diverticulum to the Vestibular Recess: A Study Using Serial Sagittal Sections of Human Embryos and Fetuses. AB - A cecum-like protrusion of the pharynx (the laryngeal cecum or vestibular recess [VR]) develops immediately anterior to the laryngeal part of the respiratory diverticulum. An expansion of the VR has been well described, whereas the fate of the diverticulum is still obscure, although its pharyngeal opening corresponds to the glottis. We observed sagittal sections of 10 embryos (five specimens at 5-6 weeks and another five at 7-8 weeks) and eight fetuses at 25-30 weeks. At 5-6 weeks, a lumen of the laryngeal part of the respiratory diverticulum appeared, and subsequently, the VR opened into the epithelial lamina. Because of this discrete separation, it seemed unlikely that the pharyngeal pouches contributed to the laryngeal epithelium. At 6-7 weeks, the VR exhibited a high boot-shaped lumen with canalization to the diverticular lumen at the level of the cricoid cartilage. Thus, in a midline area between the bilateral arytenoid cartilages, double laryngeal lumina were evident, separated by the thick midline epithelial lamina. At 25-30 weeks, the inferior part of the VR lumen had become enlarged because of the destruction of the epithelial lamina along the arytenoid and corniculate cartilages. In contrast, candidates for the initial diverticular lumen remained as epithelial slits in the anterosuperior side of the transverse arytenoid muscle. Therefore, the final anterior and lateral laryngeal walls seemed to originate from the VR with canalization, in contrast to the part of the posterior wall derived from the initial diverticular wall. PMID- 26154763 TI - Global Reprogramming of Transcription in Chinese Fir (Cunninghamia lanceolata) during Progressive Drought Stress and after Rewatering. AB - Chinese fir (Cunninghamia lanceolata), an evergreen conifer, is the most commonly grown afforestation species in southeast China due to its rapid growth and good wood qualities. To gain a better understanding of the drought-signalling pathway and the molecular metabolic reactions involved in the drought response, we performed a genome-wide transcription analysis using RNA sequence data. In this study, Chinese fir plantlets were subjected to progressively prolonged drought stress, up to 15 d, followed by rewatering under controlled environmental conditions. Based on observed morphological changes, plantlets experienced mild, moderate, or severe water stress before rehydration. Transcriptome analysis of plantlets, representing control and mild, moderate, and severe drought-stress treatments, and the rewatered plantlets, identified several thousand genes whose expression was altered in response to drought stress. Many genes whose expression was tightly coupled to the levels of drought stress were identified, suggesting involvement in Chinese fir drought adaptation responses. These genes were associated with transcription factors, signal transport, stress kinases, phytohormone signalling, and defence/stress response. The present study provides the most comprehensive transcriptome resource and the first dynamic transcriptome profiles of Chinese fir under drought stress. The drought-responsive genes identified in this study could provide further information for understanding the mechanisms of drought tolerance in Chinese fir. PMID- 26154764 TI - Molecular Characterization, mRNA Expression and Alternative Splicing of Ryanodine Receptor Gene in the Brown Citrus Aphid, Toxoptera citricida (Kirkaldy). AB - Ryanodine receptors (RyRs) play a critical role in regulating the release of intracellular calcium, which enables them to be effectively targeted by the two novel classes of insecticides, phthalic acid diamides and anthranilic diamides. However, less information is available about this target site in insects, although the sequence and structure information of target molecules are essential for designing new control agents of high selectivity and efficiency, as well as low non-target toxicity. Here, we provided sufficient information about the coding sequence and molecular structures of RyR in T. citricida (TciRyR), an economically important pest. The full-length TciRyR cDNA was characterized with an open reading frame of 15,306 nucleotides, encoding 5101 amino acid residues. TciRyR was predicted to embrace all the hallmarks of ryanodine receptor, typically as the conserved C-terminal domain with consensus calcium-biding EF hands (calcium-binding motif) and six transmembrane domains, as well as a large N terminal domain. qPCR analysis revealed that the highest mRNA expression levels of TciRyR were observed in the adults, especially in the heads. Alternative splicing in TciRyR was evidenced by an alternatively spliced exon, resulting from intron retention, which was different from the case of RyR in Myzus persicae characterized with no alternative splicing events. Diagnostic PCR analysis indicated that the splicing of this exon was not only regulated in a body specific manner but also in a stage-dependent manner. Taken together, these results provide useful information for new insecticide design and further insights into the molecular basis of insecticide action. PMID- 26154765 TI - Saxitoxin Modulates Immunological Parameters and Gene Transcription in Mytilus chilensis Hemocytes. AB - Saxitoxin (STX) is a neurotoxin produced by dinoflagellates in diverse species, such as Alexandrium spp., and it causes paralytic shellfish poisoning (PSP) in humans after the ingestion of contaminated shellfish. Recent studies have suggested that the immune functions of bivalves could be affected by harmful algae and/or by their toxins. Herein, hemocytes are the main effector cells of the immune cellular response. In this study, we evaluated the response of hemocytes from the mussel Mytilus chilensis to STX exposure in a primary culture. Cell cultures were characterized according to size and complexity, while reactive oxygen species (ROS) production was evaluated using a dichlorofluorescein diacetate (DCFH-DA) assay. Finally, phagocytic activity was measured using both flow cytometry and fluorescence microscopy assays. Additionally, gene transcription of candidate genes was evaluated by qPCR assays. The results evidenced that exposures to different concentrations of STX (1-100 nM) for 24 h did not affect cell viability, as determined by an MTT assay. However, when hemocytes were exposed for 4 or 16 h to STX (1-100 nM), there was a modulation of phagocytic activity and ROS production. Moreover, hemocytes exposed to 100 nM of STX for 4 or 16 h showed a significant increase in transcript levels of genes encoding for antioxidant enzymes (SOD, CAT), mitochondrial enzymes (COI, COIII, CYTB, ATP6, ND1) and ion channels (K+, Ca2+). Meanwhile, C-type lectin and toll like receptor genes revealed a bi-phase transcriptional response after 16 and 24 48 h of exposure to STX. These results suggest that STX can negatively affect the immunocompetence of M. chilensis hemocytes, which were capable of responding to STX exposure in vitro by increasing the mRNA levels of antioxidant enzymes. PMID- 26154767 TI - Interferon Beta-1a (AVONEX(r)) as a Treatment Option for Untreated Patients with Multiple Sclerosis (AXIOM): A Prospective, Observational Study. AB - The efficacy and safety of first-line disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM) trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a) after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies. PMID- 26154766 TI - Function of ABA in Stomatal Defense against Biotic and Drought Stresses. AB - The plant hormone abscisic acid (ABA) regulates many key processes involved in plant development and adaptation to biotic and abiotic stresses. Under stress conditions, plants synthesize ABA in various organs and initiate defense mechanisms, such as the regulation of stomatal aperture and expression of defense related genes conferring resistance to environmental stresses. The regulation of stomatal opening and closure is important to pathogen defense and control of transpirational water loss. Recent studies using a combination of approaches, including genetics, physiology, and molecular biology, have contributed considerably to our understanding of ABA signal transduction. A number of proteins associated with ABA signaling and responses--especially ABA receptors- have been identified. ABA signal transduction initiates signal perception by ABA receptors and transfer via downstream proteins, including protein kinases and phosphatases. In the present review, we focus on the function of ABA in stomatal defense against biotic and abiotic stresses, through analysis of each ABA signal component and the relationships of these components in the complex network of interactions. In particular, two ABA signal pathway models in response to biotic and abiotic stress were proposed, from stress signaling to stomatal closure, involving the pyrabactin resistance (PYR)/PYR-like (PYL) or regulatory component of ABA receptor (RCAR) family proteins, 2C-type protein phosphatases, and SnRK2 type protein kinases. PMID- 26154768 TI - Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats. AB - Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression. PMID- 26154769 TI - Perioperative Management of Antiplatelets and Anticoagulants Among Patients Undergoing Elective Transurethral Resection of the Prostate--A Single Institution Experience. AB - PURPOSE: To evaluate current practice in the perioperative management of antiplatelets (AP) and anticoagulants (AC) among men undergoing elective transurethral resection of the prostate (TURP), as well as the associated perioperative bleeding and thromboembolic complications. PATIENTS AND METHODS: Retrospective review of consecutive elective TURP patients in a single tertiary institution from January 2011 to December 2013 (n = 293). Data on the regular use of AP/AC and the perioperative management approach were collected from patients' electronic medical records. Bleeding and thromboembolic complications were assessed up to 30 days postoperative. Association between AP/AC use and perioperative complications was assessed using the Kruskall-Wallis test (continuous variables) and the Fisher exact test (categoric variables). RESULTS: There were 107/293 (37%) patients receiving long-term AP while there were 25/293 (9%) patients receiving long-term AC. A total of 72/107 (67%) patients ceased AP on an average of 7.6 days preoperatively, while 35/107 (33%) continued receiving AP. Patients with coronary stents (62%) and coronary bypass graft (67%) were significantly more likely to continued receiving AP (P < 0.001). AC was ceased in all patients preoperatively, with 16/25 (64%) receiving enoxaparin bridging. Overall, there were 31 (10%) incidents of bleeding complications and 5 (2%) thromboembolic events. AC users who had enoxaparin bridging had significantly higher risk of bleeding complications (44%), compared with non-AP/AC users (8%), AP users who ceased AP (4%), AP users who continued receiving AP (17%), and AC users who did not receive enoxaparin bridging (0%) (P < 0.001). AC users who received enoxaparin bridging also reported significantly higher thromboembolic complications (17%; P < 0.001) and prolonged hospital stay (mean 5.4 days) (P = 0.002), compared with other patients. CONCLUSION: Perioperative management of AP/AC should be based on the indications and the American College of Chest Physicians thromboembolic risk stratification. Regular AC users who had enoxaparin bridging are at increased risk of both perioperative bleeding and thromboembolic complications. PMID- 26154770 TI - Comparison between isolation protocols highlights intrinsic variability of human umbilical cord mesenchymal cells. AB - Mesenchymal stem cells (MSCs) though multipotent exhibit limited lifespan in vitro, with progressive reduction in capacity for self-renewal leading to irreversible arrest of cell division, which limits their use for therapeutic purposes. Human umbilical cord wall MSCs are easy to process and proliferate rapidly in culture, but variability of individual samples and impact upon in vitro expansion and aging processes is unknown. We compared isolation protocols to determine which one yields the highest number of viable cells with the best proliferation capacity. Three different protocols were tested: two were enzymatic procedures and one explant method. Isolated cells were evaluated in terms of proliferation, differentiation capacity, and phenotype. All samples were processed using one or more protocols. After passage 2 adherent cells displayed standard phenotypic and differentiation characteristics of MSCs, but our results show that isolating cells directly from Wharton's jelly is more advantageous. Cells obtained from explants presented similar characteristics to those from enzymatic protocols, but always reached proliferation arrest earlier, irrespective of initial population doubling times. From the same sample, cells obtained with enzymatic protocol ii reached later passages while exhibiting shorter doubling times in culture than cells from other protocols, that is, took longer to reach senescence. More important, each individual MSC sample exhibited different population doubling rates and reached senescence at different passages, irrespective of protocol. Thus, even when in strict conformity with procedures and quality control, each cord sample shows a unique behavior, a finding that should be taken into account when planning for therapeutic approaches. PMID- 26154771 TI - Recall Bias in Patients with Chronic Low Back Pain: Individual Pain Response Patterns Are More Important Than Pain Itself! AB - BACKGROUND: Patients' cognitive processing of pain-related information as well as their cognitive, affective and behavioral response pattern when experiencing pain in daily life has been shown to be associated with poorer prognosis in low back pain. However, the relationship between specific cognitive processes such as recall of pain-related material and individual pain responses remains unknown. PURPOSE: The present study sought to investigate recall bias in patients with chronic low back pain (CLBP) compared to healthy controls. Furthermore, it was aimed to investigate the impact of patients' individual pain-related responses on recall bias, comparing fear-avoidance response (FAR), endurance response (ER) and adaptive response (AR) patterns. METHOD: Thirty-one CLBP patients and 31 controls were tested on a free recall task with three word lists comprising pain words and neutral words. Further, the CLBP group was classified into patients with a FAR, ER and AR pattern, using a short screening including the Avoidance-Endurance Questionnaire (AEQ). Group differences with pain status (CLBP vs. healthy) and AEQ responses (FAR, ER, AR) as between-group factors, word type (pain vs. neutral) as within-group factor and free recall as dependent variable were analysed by means of repeated-measures analysis of (co-) variance. RESULTS: Results revealed different pain processing of pain words between FAR and ER patterns, whereas CLBP patients as a whole did not differ from the healthy controls. FAR patients displayed significantly less recall than ER patients. CONCLUSION: Recall biases in CLBP patients are not only a result of experiencing pain but also effected by patients' pain response pattern with respect to fear avoidance versus endurance. PMID- 26154773 TI - The Influence of Polymorphisms of Interleukin-17A and -17F Genes on Susceptibility and Activity of Rheumatoid Arthritis. AB - BACKGROUND: The roles of interleukin (IL)-17A and IL-17F in the pathogenesis of rheumatoid arthritis (RA) have been previously studied. However, the relationships between polymorphisms (IL-17A G197A, the IL-17F 7488A/G, and the IL 17F 7383A/G) of these genes with RA have not been clarified yet. AIMS: To investigate the impacts of these polymorphisms on the severity and susceptibility of RA in a Turkish population. METHODS: One hundred sixty-one patients with RA and 88 healthy sex-, age-, and ethnicity-matched controls were enrolled in this study. The erythrocyte sedimentation rate, C-reactive protein (CRP), and disease activity scores 28 (DAS28) of all participants were recorded. The IL-17A G197A, the IL-17F 7488A/G, and 7383A/G polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: We found no significant difference regarding genotypes or allelic frequency distributions of the IL-17A G197A, the IL-17F 7383A/G, and 7488A/G polymorphisms between patients and healthy controls (p>0.05). There were slight, but not significant, differences in terms of CRP levels associated with the distribution of the genotypes of the IL-17F 7488A/G, and regarding DAS28 levels according to the genotype distribution of the IL-17A G197A polymorphism (p=0.062, 0.087, 0.052, respectively). CONCLUSIONS: These findings suggest that future larger scale studies with increased power should be performed to determine if the IL-17F 7488A/G and the IL-17A G197A polymorphisms are associated with the disease activity in patients with RA. PMID- 26154774 TI - Membrane-less microfiltration using inertial microfluidics. AB - Microfiltration is a ubiquitous and often crucial part of many industrial processes, including biopharmaceutical manufacturing. Yet, all existing filtration systems suffer from the issue of membrane clogging, which fundamentally limits the efficiency and reliability of the filtration process. Herein, we report the development of a membrane-less microfiltration system by massively parallelizing inertial microfluidics to achieve a macroscopic volume processing rates (~ 500 mL/min). We demonstrated the systems engineered for CHO (10-20 MUm) and yeast (3-5 MUm) cells filtration, which are two main cell types used for large-scale bioreactors. Our proposed system can replace existing filtration membrane and provide passive (no external force fields), continuous filtration, thus eliminating the need for membrane replacement. This platform has the desirable combinations of high throughput, low-cost, and scalability, making it compatible for a myriad of microfiltration applications and industrial purposes. PMID- 26154775 TI - Influence of age on respiratory modulation of muscle sympathetic nerve activity, blood pressure and baroreflex function in humans. AB - NEW FINDINGS: What is the central question of this study? Does ageing influence the respiratory-related bursting of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure (Traube-Hering waves) that occur with respiration? What is the main finding and its importance? Despite the age-related elevation in MSNA, the cyclical inhibition of MSNA during respiration is similar between young and older individuals. Furthermore, central respiratory-sympathetic coupling plays a role in the generation of Traube-Hering waves in both young and older humans. Healthy ageing and alterations in respiratory-sympathetic coupling have been independently linked with heightened sympathetic neural vasoconstrictor activity. We investigated how age influences the respiratory-related modulation of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure that occur with respiration (Traube Hering waves; THW). Ten young (22 +/- 2 years; mean +/- SD) and 10 older healthy men (58 +/- 6 years) were studied while resting supine and breathing spontaneously. MSNA, blood pressure and respiration were recorded simultaneously. Resting values were ascertained and respiratory cycle-triggered averaging of MSNA and blood pressure measurements performed. The MSNA burst incidence was higher in older individuals [22.7 +/- 9.2 versus 42.2 +/- 13.7 bursts (100 heart beats)( 1), P < 0.05], and was reduced to a similar extent in the inspiratory to postinspiratory period in young and older subjects (by ~ 25% compared with mid- to late expiration). A similar attenuation of MSNA burst frequency (in bursts per minute), amplitude and total activity (burst frequency * mean burst amplitude) was also observed in the inspiratory to postinspiratory period in both groups. A significant positive correlation between respiratory-related MSNA and the magnitude of Traube-Hering waves was observed in all young (100%) and most older subjects (80%). These data suggest that the strength of the cyclical inhibition of MSNA during respiration is similar between young and older individuals; thus, alterations in respiratory-sympathetic coupling appear not to contribute to the age-related elevation in MSNA. Furthermore, central respiratory-sympathetic coupling plays a role in the generation of Traube-Hering waves in both healthy young and older humans. PMID- 26154776 TI - Fructooligosaccharides exert intestinal anti-inflammatory activity in the CD4+ CD62L+ T cell transfer model of colitis in C57BL/6J mice. AB - PURPOSE: Fructooligosaccharides (FOS) are used as functional foods due to their prebiotic effects. Intestinal anti-inflammatory activity has been established in most, but not all, studies in animal models of colitis, using mainly chemically induced inflammation. Our goal was to test the effect of FOS (degree of polymerization 2-8) in the chronic, lymphocyte-driven CD4+ CD62L+ T cell transfer model of colitis. METHODS: Colitis was induced by transfer of CD4+ CD62L+ T cells to C57BL/6J Rag1(-/-) mice. FOS (75 mg day(-1)) was administered by gavage as a post-treatment. Three groups were established: non-colitic (NC), colitic control (C, CD4+ CD62L+ transferred mice treated with vehicle) and colitic+FOS (C+FOS, similar but treated with FOS). Mice were killed after 13 days. RESULTS: Treatment of mice with FOS ameliorated colitis, as evidenced by an increase in body weight, a lesser myeloperoxidase and alkaline phosphatase activities, a lower secretion of proinflammatory cytokines by mesenteric lymph node cells ex vivo (IFN-gamma, IL-17, and TNF-alpha), and a higher colonic expression of occludin (C+FOS vs. C, p < 0.05). Increased relative abundance of lactic acid bacteria was observed in FOS-treated mice (p < 0.05). CONCLUSIONS: FOS exert intestinal anti-inflammatory activity in T lymphocyte-dependent colitis, suggesting it may be useful in the management of inflammatory bowel disease in appropriate conditions. PMID- 26154778 TI - AgBi(WO4)2 : A New Modification Material to Bi2 WO6 for Enhanced and Stable Visible-Light Photocatalyic Performance. AB - In this work, we report a novel AgBi(WO4 )2 -Bi2 WO6 heterostructure, which was designed and synthesized by using a simple hydrothermal method. Methyl orange was used as a representative dye indicator to evaluate the visible-light catalytic activity and the catalytic mechanism was investigated. The as-synthesized AgBi(WO4 )2 -Bi2 WO6 composite displayed a 43 times higher photocatalytic activity than Bi2 WO6 . Owing to the matched band gap and distinctive heterostructure, AgBi(WO4 )2 -Bi2 WO6 reveals a high visible-light response and high-efficiency utilization of both photogenerated electrons and holes. AgBi(WO4 )2 reveals a similar energy level to and good lattice match with Bi2 WO6 , which are favorable qualities for band bending and fluent electron transfer. Furthermore, the photoexcited electrons can produce oxygen to generate (.) O2 (-) radicals, which is vital for the overall utilization of both holes and electrons. This is the first example of AgBi(WO4 )2 being used as photocatalytic material. PMID- 26154777 TI - Food protein-derived bioactive peptides in management of type 2 diabetes. AB - BACKGROUND: Type 2 diabetes (T2D), one of the major common human health problems, is growing at an alarming rate around the globe. Alpha-glucosidase and dipeptidyl peptidase IV (DPP-IV) enzymes play a significant role in development of T2D. Hence, reduction or inhibition of their activity can be one of the important strategies in management of T2D. Studies in the field of bioactive peptides have shown that dietary proteins could be natural source of alpha-glucosidase and DPP IV inhibitory peptides. PURPOSE: The purpose of this review is to provide an overview of food protein-derived peptides as potential inhibitors of alpha glucosidase and DPP-IV with major focus on milk proteins. METHODS: Efforts have been made to review the available information in literature on the relationship between food protein-derived peptides and T2D. This review summarizes the current data on alpha-glucosidase and dipeptidyl peptidase IV inhibitory bioactive peptides derived from proteins and examines the potential value of these peptides in the treatment and prevention of T2D. In addition, the proposed modes of inhibition of peptide inhibitors are also discussed. RESULTS: Studies revealed that milk and other food proteins-derived bioactive peptides play a vital role in controlling T2D through several mechanisms, such as the satiety response, regulation of incretin hormones, insulinemia levels, and reducing the activity of carbohydrate degrading digestive enzymes. CONCLUSIONS: The bioactive peptides could be used in prevention and management of T2D through functional foods or nutraceutical supplements. Further clinical trials are necessary to validate the findings of in vitro studies and to confirm the efficiency of these peptides for applications. PMID- 26154779 TI - Serpentinization and the Formation of H2 and CH4 on Celestial Bodies (Planets, Moons, Comets). AB - Serpentinization involves the hydrolysis and transformation of primary ferromagnesian minerals such as olivine ((Mg,Fe)2SiO4) and pyroxenes ((Mg,Fe)SiO3) to produce H2-rich fluids and a variety of secondary minerals over a wide range of environmental conditions. The continual and elevated production of H2 is capable of reducing carbon, thus initiating an inorganic pathway to produce organic compounds. The production of H2 and H2-dependent CH4 in serpentinization systems has received significant interdisciplinary interest, especially with regard to the abiotic synthesis of organic compounds and the origins and maintenance of life in Earth's lithosphere and elsewhere in the Universe. Here, serpentinization with an emphasis on the formation of H2 and CH4 are reviewed within the context of the mineralogy, temperature/pressure, and fluid/gas chemistry present in planetary environments. Whether deep in Earth's interior or in Kuiper Belt Objects in space, serpentinization is a feasible process to invoke as a means of producing astrobiologically indispensable H2 capable of reducing carbon to organic compounds. PMID- 26154781 TI - Localized juvenile spongiotic gingival hyperplasia possibly originates from the junctional gingival epithelium-an immunohistochemical study. AB - AIMS: To immunohistochemically evaluate the cytokeratin (CK) pattern of expression in localized juvenile spongiotic gingival hyperplasia (LJSGH) as compared with the gingival epithelium (GE). METHODS AND RESULTS: Ten cases of LJSGH were semiquantitatively evaluated for the immunohistochemical pattern of CK1/10, CK4, CK8/18, and CK19. GE controls were taken from 10 cases of reactive gingival fibroepithelial hyperplasia. GEs showed mean positivity rates of 80% for both CK1/10 and CK4, and 5% for both CK8/18 and CK19. LJSGHs showed mean positivity rates of 65% for CK19, 60% for CK8/18, 30% for CK4, and 5% for CK1/10. The differences between LJSGHs and GEs were statistically significant (P < 0.01). CONCLUSIONS: The LJSGH pattern of CK expression is reminiscent of the profile described in the literature for the junctional epithelium (JE). Possibly, JE exteriorized from the gingival sulcus would be more prone to irritation from a variety of sources, resulting in inflammation and hyperplasia, with the subsequent development of LJSGH. PMID- 26154782 TI - Gametic interactions promote inbreeding avoidance in house mice. AB - Reproduction among related individuals is generally maladaptive. Inbreeding imposes significant costs on individual reproductive success, and can decrease population fitness. Theory predicts that polyandrous females can avoid inbreeding by exploiting paternity-biasing mechanisms that enable differential sperm 'use'. Evidence of sperm selection is difficult to demonstrate because patterns of non random paternity can be generated by a variety of different mechanisms. Here, using in vitro fertilisation in mice, we provide evidence of sperm selection at the gametic level. We mixed the sperm of sibling and non-sibling males, and observed a fertilisation bias towards the sperm of non-sibling males. The number of motile sperm and sperm swimming performance did not differ between competitors among the replicate assays. Therefore, our result can only be ascribed to egg driven sperm selection against related sperm. We conclude that the expression or secretion of gametic proteins could provide the molecular basis for this mechanism of cryptic female choice. PMID- 26154780 TI - Retromer-Mediated Trafficking of Transmembrane Receptors and Transporters. AB - Transport between the endoplasmatic reticulum, the Golgi-network, the endo lysosomal system and the cell surface can be categorized as anterograde or retrograde, describing traffic that goes forward or backward, respectively. Traffic going from the plasma membrane to endosomes and lysosomes or the trans Golgi network (TGN) constitutes the major retrograde transport routes. Several transmembrane proteins undergo retrograde transport as part of a recycling mechanism that contributes to reutilization and maintenance of a steady-state protein localization. In addition, some receptors are hijacked by exotoxins and used for entry and intracellular transport. The physiological relevance of retrograde transport cannot be overstated. Retrograde trafficking of the amyloid precursor protein determines the distribution between organelles, and hence the possibility of cleavage by gamma-secretase. Right balancing of the pathways is critical for protection against Alzheimer's disease. During embryonic development, retrograde transport of Wntless to the TGN is essential for the following release of Wnt from the plasma membrane. Furthermore, overexpression of Wntless has been linked to oncogenesis. Here, we review relevant aspects of the retrograde trafficking of mammalian transmembrane receptors and transporters, with focus on the retromer-mediated transport between endosomes and the TGN. PMID- 26154783 TI - A Spotlight on Sunscreen Regulation. PMID- 26154784 TI - Synthetic Cannabinoid-Related Illnesses and Deaths. PMID- 26154785 TI - Breaking Up Is Hard to Do. PMID- 26154786 TI - Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. METHODS: We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 >=80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. RESULTS: Among 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (+/-SD) decline of 53+/-21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27+/-18 ml per year (P<0.001), despite similar smoking exposure. CONCLUSIONS: Our study suggests that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.). PMID- 26154787 TI - A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis. AB - BACKGROUND: Little is known about the effect of specific anti-interleukin-23 therapy, as compared with established anti-tumor necrosis factor therapies, for the treatment of moderate-to-severe plaque psoriasis. METHODS: In a 52-week, phase 2, dose-ranging, randomized, double-blind, placebo-controlled, active comparator trial, we compared guselkumab (CNTO 1959), an anti-interleukin-23 monoclonal antibody, with adalimumab in patients with moderate-to-severe plaque psoriasis. A total of 293 patients were randomly assigned to receive guselkumab (5 mg at weeks 0 and 4 and every 12 weeks thereafter, 15 mg every 8 weeks, 50 mg at weeks 0 and 4 and every 12 weeks thereafter, 100 mg every 8 weeks, or 200 mg at weeks 0 and 4 and every 12 weeks thereafter) through week 40, placebo, or adalimumab (standard dosage for psoriasis). At week 16, patients in the placebo group crossed over to receive guselkumab at a dose of 100 mg every 8 weeks. The primary end point was the proportion of patients with a Physician's Global Assessment (PGA) score of 0 (indicating cleared psoriasis) or 1 (indicating minimal psoriasis) at week 16. RESULTS: At week 16, the proportion of patients with a PGA score of 0 or 1 was significantly higher in each guselkumab group than in the placebo group: 34% in the 5-mg group, 61% in the 15-mg group, 79% in the 50-mg group, 86% in the 100-mg group, and 83% in the 200-mg group, as compared with 7% in the placebo group (P<=0.002 for all comparisons). Moreover, the proportion was significantly higher in the 50-mg, 100-mg, and 200-mg guselkumab groups than in the adalimumab group (58%) (P<0.05 for all comparisons). At week 16, the proportion of patients with at least a 75% improvement in Psoriasis Area and Severity Index scores was significantly higher in each guselkumab group than in the placebo group (P<0.001 for all comparisons). At week 40, the proportion of patients with a PGA score of 0 or 1 remained significantly higher in the 50-mg, 100-mg, and 200-mg guselkumab groups than in the adalimumab group (71%, 77%, and 81%, respectively, vs. 49%) (P<0.05 for all comparisons). Between week 0 and week 16, infections were observed in 20% of the patients in the guselkumab groups, 12% in the adalimumab group, and 14% in the placebo group. CONCLUSIONS: The results of this phase 2 trial suggest that guselkumab may be an effective therapy for plaque psoriasis and that control of psoriasis can be achieved with specific anti interleukin-23 therapy. (Funded by Janssen Research and Development; X-PLORE ClinicalTrials.gov number, NCT01483599.). PMID- 26154788 TI - A Variegated Squirrel Bornavirus Associated with Fatal Human Encephalitis. AB - Between 2011 and 2013, three breeders of variegated squirrels (Sciurus variegatoides) had encephalitis with similar clinical signs and died 2 to 4 months after onset of the clinical symptoms. With the use of a metagenomic approach that incorporated next-generation sequencing and real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), the presence of a previously unknown bornavirus was detected in a contact squirrel and in brain samples from the three patients. Phylogenetic analyses showed that this virus, tentatively named variegated squirrel 1 bornavirus (VSBV-1), forms a lineage separate from that of the known bornavirus species. (Funded by the Federal Ministry of Food and Agriculture [Germany] and others.). PMID- 26154789 TI - Mast Cells, Mastocytosis, and Related Disorders. PMID- 26154790 TI - IMAGES IN CLINICAL MEDICINE. Diffuse Soft-Tissue Calcinosis. PMID- 26154791 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 21-2015. A 37-Year-Old American Man Living in Vietnam, with Fever and Bacteremia. PMID- 26154792 TI - Exploring Different Phenotypes of COPD. PMID- 26154793 TI - Inhibition of Lactate Dehydrogenase to Treat Epilepsy. PMID- 26154794 TI - Liberal or Restrictive Transfusion after Cardiac Surgery. PMID- 26154795 TI - Liberal or Restrictive Transfusion after Cardiac Surgery. PMID- 26154796 TI - Liberal or Restrictive Transfusion after Cardiac Surgery. PMID- 26154797 TI - Liberal or Restrictive Transfusion after Cardiac Surgery. PMID- 26154798 TI - Liberal or Restrictive Transfusion after Cardiac Surgery. PMID- 26154799 TI - Liberal or Restrictive Transfusion after Cardiac Surgery. PMID- 26154800 TI - Liberal or Restrictive Transfusion after Cardiac Surgery. PMID- 26154801 TI - Cancers Complicating Inflammatory Bowel Disease. PMID- 26154802 TI - Cancers Complicating Inflammatory Bowel Disease. PMID- 26154803 TI - A Randomized Trial of Laparoscopic versus Open Surgery for Rectal Cancer. PMID- 26154804 TI - A Randomized Trial of Laparoscopic versus Open Surgery for Rectal Cancer. PMID- 26154805 TI - Molecular Physiology of Water Balance. PMID- 26154806 TI - Molecular Physiology of Water Balance. PMID- 26154808 TI - Follow-Up of Glycemic Control and Cardiovascular Outcomes in Type 2 Diabetes. PMID- 26154807 TI - Sunscreen and the FDA. PMID- 26154809 TI - Integrated Ambulatory Specialist Care--Germany's New Health Care Sector. PMID- 26154810 TI - IMAGES IN CLINICAL MEDICINE. Coral Dermatitis. PMID- 26154812 TI - Childhood trauma are not associated with the intensity of transient cocaine induced psychotic symptoms. AB - A personal history of childhood trauma has been associated with the severity of psychotic symptoms in several disorders. We evaluated retrospectively cocaine induced psychotic symptoms with the SAPS-CIP and childhood trauma with the CTQ in a clinical sample of 144 cocaine users. The SAPS-CIP score was not statistically associated with the presence or number or intensity of trauma, but was associated with rapid routes of administration (intravenous and smoked) and with frequent cocaine use. PMID- 26154811 TI - Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes. AB - Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) to rapidly profile the entire intestinal topography and assess inflammation. We examine the mucosal surface of >700 mice (encompassing >16 strains and various IBD-models), create a profiling catalogue of 3D-stereomicroscopic abnormalities and demonstrate that mice with comparable histological scores display unique sub clusters of 3D-structure-patterns of IBD pathology, which we call 3D stereoenterotypes, and which are otherwise indiscernible histologically. We show that two ileal IBD-stereoenterotypes ('cobblestones' versus 'villous mini aggregation') cluster separately within two distinct mouse lines of spontaneous ileitis, suggesting that host genetics drive unique and divergent inflammatory 3D structural patterns in the gut. In humans, stereomicroscopy reveals 'liquefaction' lesions and hierarchical fistulous complexes, enriched with clostridia/segmented filamentous bacteria, running under healthy mucosa in Crohn's disease. We suggest that stereomicroscopic (3D-SMAPgut) profiling can be easily implemented and enable the comprehensive study of inflammatory 3D structures, genetics and flora in IBD. PMID- 26154813 TI - ASMT gene polymorphisms have no association with schizophrenia in a Han Chinese sample. PMID- 26154814 TI - Neutrophil-lymphocyte and platelet-lymphocyte ratios as inflammation markers for bipolar disorder. AB - In the present study we investigated the involvement of inflammatory cells and their ratios as inflammation markers in Bipolar Disorder. We have enrolled 61 manic, 55 euthymic patients and 54 control subjects to the study. Neutrophil lymphocyte and platelet-lymphocyte ratios were found significantly higher in both manic and euthymic patients compared to control group. These findings suggest that the inflammatory cells have a role in the pathophysiology of bipolar disorder manic and even in euthymic state. PMID- 26154815 TI - Cannabis use, schizotypy, and negative priming. AB - The present study examined the effects of frequency of cannabis use, schizotypy, and age on cognitive control, as measured using a location-based negative priming task in a sample of 124 Australians aged 15-24 who had ever used cannabis. This study found that the schizotypy dimension of Impulsive Nonconformity had a significant effect on negative priming such that participants with higher scores on this dimension showed reduced negative priming. Also, higher levels of psychological distress were associated with greater negative priming. Finally, there was a significant age by cannabis use interaction indicating that younger, frequent users of cannabis may be more susceptible to its effects on cognitive control and perhaps at greater risk of developing a disorder on the psychosis dimension. PMID- 26154816 TI - A randomised trial of nutrient supplements to minimise psychological stress after a natural disaster. AB - After devastating flooding in southern Alberta in June 2013, we attempted to replicate a New Zealand randomised trial that showed that micronutrient (minerals, vitamins) consumption after the earthquakes of 2010-11 resulted in improved mental health. Residents of southern Alberta were invited to participate in a study on the potential benefit of nutrient supplements following a natural disaster. Fifty-six adults aged 23-66 were randomised to receive a single nutrient (vitamin D, n=17), a few-nutrients formula (B-Complex, n=21), or a broad spectrum mineral/vitamin formula (BSMV, n=18). Self-reported changes in depression, anxiety and stress were monitored for six weeks. Although all groups showed substantial decreases on all measures, those consuming the B-Complex and the BSMV formulas showed significantly greater improvement in stress and anxiety compared with those consuming the single nutrient, with large effect sizes (Cohen's d range 0.76-1.08). There were no group differences between those consuming the B-Complex and BSMV. The use of nutrient formulas with multiple minerals and/or vitamins to minimise stress associated with natural disasters is now supported by three studies. Further research should be carried out to evaluate the potential population benefit that might accrue if such formulas were distributed as a post-disaster public health measure. PMID- 26154817 TI - Examining the unique relations between anxiety sensitivity factors and suicidal ideation and past suicide attempts. AB - Anxiety sensitivity (AS) has recently been linked to suicidality. Specifically, AS cognitive concerns has been implicated as a risk factor, and AS physical concerns as a protective factor, for suicidal ideation and suicide attempts. However, no studies have used structural equation modeling (SEM) to address issues of skewed suicide variables and bifactor modeling of AS to address the high degree of overlap between the lower-order dimensions of AS that limit interpretation of these past findings. AS, suicidal ideation, past suicide attempts, and depression were assessed in a clinical sample of 267 individuals (M age=35.45 years, SD=16.53; 52.1% female). The global AS and AS cognitive concerns factors were positively, significantly associated with suicidal ideation, though these effects were nonsignificant controlling for depression. The global AS factor was positively, significantly associated with suicide attempts, controlling for depression. The current study demonstrated that the relations between AS and suicidal ideation are not maintained when accounting for depression, suggesting that the relation between AS and suicidal ideation may be mediated by depression. The positive relation between global AS and suicide attempts is consistent with theories positing suicide attempts as a consequence of an inability to cope with intolerable distress. PMID- 26154818 TI - No evidence for mirror system dysfunction in schizophrenia from a multimodal TMS/EEG study. AB - Dysfunctional mirror neuron systems have been proposed to contribute to the social cognitive deficits observed in schizophrenia. A few studies have explored mirror systems in schizophrenia using various techniques such as TMS (levels of motor resonance) or EEG (levels of mu suppression), with mixed results. This study aimed to use a novel multimodal approach (i.e. concurrent TMS and EEG) to further investigate mirror systems and social cognition in schizophrenia. Nineteen individuals with schizophrenia or schizoaffective disorder and 19 healthy controls participated. Single-pulse TMS was applied to M1 during the observation of hand movements designed to elicit mirror system activity. Single EEG electrodes (C3, CZ, C4) recorded brain activity. Participants also completed facial affect recognition and theory of mind tasks. The schizophrenia group showed significant deficits in facial affect recognition and higher level theory of mind compared to healthy controls. A significant positive relationship was revealed between mu suppression and motor resonance for the overall sample, indicating concurrent validity of these measures. Levels of mu suppression and motor resonance were not significantly different between groups. These findings indicate that in stable outpatients with schizophrenia, mirror system functioning is intact, and therefore their social cognitive difficulties may be caused by alternative pathophysiology. PMID- 26154819 TI - Stress induced by the socially evaluated cold-pressor test cause equivalent deficiencies of sensory gating in male subjects with schizophrenia and healthy controls. AB - It is known that patients with schizophrenia show a deficiency in the prepulse inhibition reflex (PPI). These patients display abnormalities in autonomic nervous system and hypothalamic-pituitary-adrenal function and may have an altered sensitivity to stress. To date, no studies have been carried out to determine the effect of acute stress on the PPI. We investigated whether there was a differential response in reactivity to acute stress caused by the socially evaluated cold-pressor test (SECPT) in a sample of 58 chronic male patients with schizophrenia and 28 healthy control subjects. PPI, salivary cortisol and heart rate (HR) were measured. The patients were evaluated in two sessions (with and without the SECPT) 72 h apart and basal measurements were carried out and 30 min post-startle probe. We found an increase in salivary cortisol levels and the HR with SECPT condition in both groups and a significantly lower PPI% in patients with schizophrenia. The most relevant findings of this study are that the impairment of the PPI is increased by stress. Stress-induced increase in cortisol in both groups, mainly in healthy control group which allows us to hypothesize that at least such deterioration may be due to the hypercortisolemia caused by the SECPT. PMID- 26154820 TI - Association between the efficacy of fluoxetine treatment in obsessive-compulsive disorder patients and SLC1A1 in a Han Chinese population. PMID- 26154822 TI - Cellulose nanocrystals with tunable surface charge for nanomedicine. AB - Crystalline nanoparticles of cellulose exhibit attractive properties as nanoscale carriers for bioactive molecules in nanobiotechnology and nanomedicine. For applications in imaging and drug delivery, surface charge is one of the most important factors affecting the performance of nanocarriers. However, current methods of preparation offer little flexibility for controlling the surface charge of cellulose nanocrystals, leading to compromised colloidal stability under physiological conditions. We report a synthesis method that results in nanocrystals with remarkably high carboxyl content (6.6 mmol g(-1)) and offers continuous control over surface charge without any adjustment to the reaction conditions. Six fractions of nanocrystals with various surface carboxyl contents were synthesized from a single sample of softwood pulp with carboxyl contents varying from 6.6 to 1.7 mmol g(-1) and were fully characterized. The proposed method resulted in highly stable colloidal nanocrystals that did not aggregate when exposed to high salt concentrations or serum-containing media. Interactions of these fractions with four different tissue cell lines were investigated over a wide range of concentrations (50-300 MUg mL(-1)). Darkfield hyperspectral imaging and confocal microscopy confirmed the uptake of nanocrystals by selected cell lines without any evidence of membrane damage or change in cell density; however a charge-dependent decrease in mitochondrial activity was observed for charge contents higher than 3.9 mmol g(-1). A high surface carboxyl content allowed for facile conjugation of fluorophores to the nanocrystals without compromising colloidal stability. The cellular uptake of fluoresceinamine-conjugated nanocrystals exhibited a time-dose dependent relationship and increased significantly with doubling of the surface charge. PMID- 26154823 TI - Thrombospondin-1 as a Regulator of Corneal Inflammation and Lymphangiogenesis: Effects on Dry Eye Disease and Corneal Graft Immunology. AB - Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that belongs to a family of evolutionary highly conserved calcium-binding proteins consisting of 5 members (TSP-1-TSP-5). In the eye, TSP-1 is expressed by several ocular cell types and is also detectable in the aqueous humor and the vitreous body. So far, TSP-1 is one of the major activators of TGFbeta, suggesting a strong influence on various important cellular functions and interactions such as differentiation, migration, and wound healing. TSP-1 is also a key endogenous inhibitor of hem- and lymphangiogenesis. Several lines of evidence indicate a crucial role of TSP-1 in maintaining the ocular immune and angiogenic privilege, for example, by regulating T lymphocytes and the tolerance-promoting properties of ocular antigen presenting cells. This review discusses the role of TSP-1 in dry eye disease and corneal graft rejection through its effects on hem- and lymphangiogenesis, as well as on the underlying immune responses. Recent work will be reviewed showing by which molecular mechanism TSP-1 modulates inflammatory processes during ocular diseases. This opens potential new treatment avenues in inflammatory and (lymph)angiogenic ocular diseases. PMID- 26154824 TI - Calcium Binding Restores Gel Formation of Succinylated Gelatin and Reduces Brittleness with Preservation of the Elastically Stored Energy. AB - To better tailor gelatins for textural characteristics in (food) gels, their interactions are destabilized by introduction of electrostatic repulsions and creation of affinity sites for calcium to "lock" intermolecular interactions. For that purpose gelatins with various degrees of succinylation are obtained. Extensive succinylation hampers helix formation and gel strength is slightly reduced. At high degrees of succinylation the helix propensity, gelling/melting temperatures, concomitant transition enthalpy, and gel strength become calcium sensitive, and relatively low calcium concentrations largely restore these properties. Although succinylation has a major impact on the brittleness of the gels formed and the addition of calcium makes the material less brittle compared to nonmodified gelatin, the modification has no impact on the energy balance in the gel, where all energy applied is elastically stored in the material. This is explained by the unaffected stress relaxation by the network and high water holding capacity related to the small mesh sizes in the gels. PMID- 26154825 TI - Bundling Payments for Episodes of Surgical Care. PMID- 26154826 TI - Feasibility of using a large amplitude movement therapy to improve ambulatory function in children with cerebral palsy. AB - Cerebral palsy (CP) is the most common cause of motor disability among children. Limited evidence exists regarding the efficacy of traditional rehabilitation strategies on improving ambulatory function in this population. The purpose of the study was to investigate the feasibility and short-term effects of a novel large amplitude movement therapy on ambulatory functions in children with CP. Temporal-spatial gait characteristics were examined before and after a single intervention session, replicated over five children. Five children with CP (7.0 +/- 1.0 years); Gross Motor Function Classification System Levels I-II, participated. Baseline gait parameters were obtained as the participant walked across an instrumented walkway at self-selected and fast speeds. Children then participated in a 20-30 min intervention focused on making body and limb movements as large as possible with gait assessment repeated immediately. All children tolerated testing and therapy with no adverse effects. Outcomes after one intervention included: significantly greater stride velocity; reduced double support time; and greater stride length after training for three of the five participants. Results for this pilot study suggested that the large amplitude movement therapy was feasible for children with CP. There is a need for a larger scale study to determine if the protocol can be effective at an appropriate clinical dose. PMID- 26154827 TI - Sphere-shaped nano-hydroxyapatite/chitosan/gelatin 3D porous scaffolds increase proliferation and osteogenic differentiation of human induced pluripotent stem cells from gingival fibroblasts. AB - Hydroxyapatite (HA) is an important component of human bone and bone tissue engineering scaffolds. A plethora of bone tissue engineering scaffolds have been synthesized so far, including nano-HA/chitosan/gelatin (nHA/CG) scaffolds; and for seeding cells, stem cells, especially induced pluripotent stem cells (iPSCs), have been a promising cell source for bone tissue engineering recently. However, the influence of different HA nano-particle morphologies on the osteogenic differentiation of human iPSCs (hiPSCs) from human gingival fibroblasts (hGFs) is unknown. The purpose of this study was to investigate the osteogenic differentiation of hiPSCs from hGFs seeded on nHA/CG scaffolds with 2 shapes (rod and sphere) of nHA particles. Firstly, hGFs isolated from discarded normal gingival tissues were reprogrammed into hiPSCs. Secondly, hiPSCs were seeded on rod-like nHA/CG (rod-nHA/CG) and sphere-shaped nHA/CG (sphere-nHA/CG) scaffolds respectively and then cell/scaffold complexes were cultured in vitro. Scanning electron microscope, hematoxyline and eosin (HE) staining, Masson's staining, and quantitative real-time polymerase chain reaction techniques were used to examine hiPSC morphology, proliferation, and differentiation on rod-nHA/CG and sphere nHA/CG scaffolds. Finally, hiPSCs composited with 2 kinds of nHA/CG were transplanted in vivo in a subcutaneous implantation model for 12 weeks; pure scaffolds were also transplanted as a blank control. HE, Masson's, and immunohistochemistry staining were applied to detect new bone regeneration ability. The results showed that sphere-nHA/CG significantly increased hiPSCs from hGF proliferation and osteogenic differentiation in vitro. hiPSCs and sphere nHA/CG composities generated large bone, whereas hiPSCs and rod-nHA/CG composities produced tiny bone in vivo. Moreover, pure scaffolds without cells almost produced no bone. In conclusion, our work provided a potential innovative bone tissue engineering approach using clinically discarded gingival tissues and sphere-nHA/CG scaffolds. PMID- 26154828 TI - Enhancing Stability of Perovskite Solar Cells to Moisture by the Facile Hydrophobic Passivation. AB - In this study, a novel and facile passivation process for a perovskite solar cell is reported. Poor stability in ambient atmosphere, which is the most critical demerit of a perovskite solar cell, is overcome by a simple passivation process using a hydrophobic polymer layer. Teflon, the hydrophobic polymer, is deposited on the top of a perovskite solar cell by a spin-coating method. With the hydrophobic passivation, the perovskite solar cell shows negligible degradation after a 30 day storage in ambient atmosphere. Suppressed degradation of the perovskite film is proved in various ways: X-ray diffraction, light absorption spectrum, and quartz crystal microbalance. This simple but effective passivation process suggests new kind of approach to enhance stability of perovskite solar cells to moisture. PMID- 26154829 TI - Educational intervention to improve oral health beliefs and behaviors during pregnancy: a randomized-controlled trial. AB - BACKGROUND: Oral and dental health is one of the most important aspects of public health, which becomes more important during pregnancy. Health education may effectively prevent a considerable percent of oral and dental diseases. OBJECTIVE: This study was designed to evaluate the effects of an oral and dental health educational intervention during pregnancy on the beliefs and behaviors of pregnant women on oral and dental health. PARTICIPANTS AND METHODS: In this randomized-controlled clinical trial, 160 pregnant women were allocated randomly to intervention and control groups (80 in each group). The intervention group received six education sessions over 3 weeks on oral health issues, whereas the control group received no education. Beliefs and behaviors of pregnant women on oral health were evaluated before, immediately, and 2 months after the educational intervention using a self-administered questionnaire containing 13 Likert scale belief statements and nine practice items. RESULTS: There were no significant differences in the scores of behaviors between the two groups, whereas the scores of beliefs of the educated group were lower than the controls at baseline. The scores of beliefs and behaviors were significantly higher in the educated group than the controls immediately and 2 months after the education program (P<0.05). CONCLUSION AND RECOMMENDATIONS: The results of the present study indicated the positive effects of oral health training during pregnancy in promoting the beliefs and behaviors of pregnant women on oral health. More attention to oral and dental education programs is recommended during pregnancy. PMID- 26154830 TI - Turnover intention among intensive care unit nurses in Alexandria, Egypt. AB - BACKGROUND: Given the difficulty in recruiting new nurses, it is imperative to retain those already in the profession. This cross-sectional study explored the relationship of demographic and work-related factors, burnout, conflict management and relationship between nurses and physicians on turnover intentions among ICU nurses in eight major hospitals in Alexandria, Egypt. SUBJECTS AND METHODS: Data on burnout, conflict management, nurse-physician communication, and turnover intention were collected by surveying 100 nurses in eight hospitals in Alexandria governorate. All nurses at the ICU of selected hospitals were approached (n=100) and a 47-item Likert scale questionnaire was administered to explore the factors affecting the turnover intention of ICU nurses in Alexandria. RESULTS: ICU nurses exhibited a mean score for turnover intention of 3.23 (mean score percentage 65.0%). There was a moderately positive statistically significant correlation between turnover intention and emotional exhaustion (r=0.29, P<0.05), nurse-physician communication (r=0.25, P<0.05), and age (r=0.21, P<0.05). The predicting factors for turnover intention were emotional exhaustion and age. CONCLUSION AND RECOMMENDATION: Nurses turnover intention at the ICU of the selected hospitals is high and is significantly associated with nurses' emotional exhaustion, poor nurse-physician communication, and nurses age. PMID- 26154831 TI - Pneumococcal infection among hospitalized Egyptian children. AB - AIM: We aimed to describe the detection rate spectrum of clinical manifestations, and outcome of pneumococcal disease in children younger than 5 years admitted to the largest referral pediatric hospital in Egypt. MATERIALS AND METHODS: This was a hospital-based study to detect laboratory-confirmed Streptococcus pneumoniae cases among children younger than 5 years. Data on demographic characteristics, clinical diagnosis, comorbidities, diagnostic tests, antibiotic resistance, and clinical outcome were collected during the study years from 2008 to 2011. RESULTS: During the 4-year study period, 22 018 cases younger than 5 years had cultures performed at Cairo University Pediatric Hospital microbiology laboratory. We estimated the annual detection rate of total Streptococcus pneumonia infection to be 54.5/100 000. The incidence of invasive pneumococcal disease (IPD) was half the incidence of non-IPD (18.2 and 36.4/100 000, respectively). Infants of 1 year or younger were statistically more vulnerable to Streptococcus pneumonia infection compared with children between 1 and 5 years of age (annual rate: 110.5/100 000 and 21.6/100 000, respectively). The overall pneumococcal annual case fatality was 33.3% and was higher in IPD (75%) than in non-IPD (12.5%) cases. There was an obviously increasing trend of the pneumococcal detection rate throughout the 4 years of the study (P<0.0001). CONCLUSION AND RECOMMENDATIONS: Our results confirm the substantial and increasing pneumococcal infection, the emerging of multidrug resistant isolates, and the vulnerability of the younger age group and high-risk population, which calls for a national surveillance to inform policy and decision-making before national wide vaccine introduction. PMID- 26154832 TI - Controlling dyspnea in chronic obstructive pulmonary disease patients. AB - BACKGROUND: Dyspnea and fatigue are the most mutual symptoms known to be present in chronic obstructive pulmonary disease (COPD) patients. COPD patients have extra trouble breathing out fully. They can apply relaxed breathing techniques any time taking a breath such as following coughing or physical activity. By training to preserve energy with daily chores, patients can perform many physical actions with less dyspnea. AIM: The aim of the current study was to assess the effect of an educational intervention on knowledge, practices, and disease severity in patients with COPD. PARTICIPANTS AND METHODS: A purposive sample of 100 adult male patients was selected randomly from the Respiratory Clinic at King Abdul-Aziz University Hospital, Jeddah. Patients were assessed using a clinical sheet, patients' dyspnea knowledge questionnaire, patients' practices observational checklists, the Modified Borg Scale, and the Hospital Anxiety and Depression Scale. RESULTS: More than 50% of patients had insufficient knowledge and 100% of them reported that they did not practice respiratory muscles exercises before the educational intervention. These improved after the intervention, showing a highly statistically significant difference. In addition, dyspnea and anxiety improved in COPD patients who had received supervised guidelines. CONCLUSION AND RECOMMENDATIONS: Application of dyspnea-management guidelines has enhanced patients' knowledge of their disease, practice, as well as dyspnea and anxiety levels. Health instruction materials for COPD patients can be useful by means of providing simplified guidelines, explanatory videos, leaflets, and/or brochures to clarify, avoid, and manage dyspnea. An additional estimate of the outcome of instructions to avoid and improve dyspnea and distress reactions in a larger sample size is proposed. PMID- 26154833 TI - Quality of delivery care in Assiut University Hospital, Egypt: mothers' satisfaction. AB - BACKGROUND: Client satisfaction is an important parameter of quality assessment, as patient's preferences and demands influence health status and medical outcomes. OBJECTIVE: The aim of this study was to assess mothers' satisfaction with the quality of healthcare during hospital delivery and its determinants. PARTICIPANTS AND METHODS: A cross-sectional design was used. Women who gave birth at Women Health Center of Assiut University Hospital during a 2-month period in 2012 (n=435) were interviewed using a semistructured questionnaire to examine various dimensions of care. RESULTS: Nearly two-third of interviewed mothers (63%) were satisfied with the quality of delivery care they received at the hospital. They would deliver again in the hospital and would recommend the hospital to others. Younger women, primipara, and highly educated were more likely to be satisfied than their counterparts. Pregnancy intendedness was associated with the satisfaction (P=0.000). Mothers' satisfaction with the way health provider treated them varied among nurses, doctors, and workers (77.7, 69.2, and 56.1%, respectively). Only 11.7% of mothers reported that they were satisfied with the health advices from the health providers, whereas 92.0% were satisfied with the competence of care providers. High satisfaction with the physical environment of the hospital was reported (>90%). CONCLUSION AND RECOMMENDATIONS: Although mothers' satisfaction with provider competence was high, satisfaction with the interpersonal aspects of the quality of care and health information given during delivery care was low. Training the physicians about the communication and interpersonal skills and emphasizing the value of providing mothers with health information are highly recommended. PMID- 26154834 TI - Physicochemical quality and health implications of bottled water brands sold in Ethiopia. AB - BACKGROUND: Water bottling companies often assert that their products are of the highest quality and are conforming to the standards. OBJECTIVES: The objective of the study was to assess the physicochemical quality of bottled waters consumed in Ethiopia and to compare the findings with the national and international water quality standards. MATERIALS AND METHODS: Eleven domestic and two imported bottled water brands were randomly purchased in Addis Ababa, Ethiopia at three different occasions from July 2013 to May 2014. A total of 39 composite samples were examined for aggregate parameters, major anions, and common cations in accordance with the procedures described in the standard methods. RESULTS: We found that 7.7% of the samples were containing higher levels of alkalinity, hardness, total dissolved solids, pH, HCO3-, Na+, and Ca2+ than the national standards and the WHO guidelines. However, the deviations from standards for all the above parameters were not statistically significant (one-sample t-test, P>0.05). Conversely, in some of the brands, some of the essential elements like Ca2+, K+, Mg2+, and F- were found at very low concentrations. The rest of the parameters, including CO3(2-), SO4(2-), PO4(3-) (orthophosphates), Cl-, F-, NO3-, NO2-, K+, Mg2+, Fe, Mn, Cr, Cd, Cu, Ni, and Pb were within the acceptable ranges in all the brands. CONCLUSION AND RECOMMENDATIONS: Bottled water brands containing very high concentrations of dissolved substances may pose health risks for individuals living with heart and kidney related problems. On the other hand, brands having chemicals lower than the optimum level may also harm the health of consumers who choose those brands as a sole source of drinking water. Thus, we suggest those responsible authorities to ensure regular monitoring and testing for chemical compositions of bottled water. PMID- 26154835 TI - Nutritional status and parasitic infestation among working children in a village in Egypt: a comparative study. AB - BACKGROUND: Work poses potential threats to the physical, emotional, economic, and academic health of teenagers. Like their adult coworkers, teenagers face exposure to a variety of health and safety hazards that can lead to injury and illness. Children's increased vulnerability puts them at a high risk of work related health problems. OBJECTIVES: The aim of this study was to compare growth parameters of working children in contrast to nonworking students, and to compare the frequency of anemia and parasitic infestations among the two groups. PARTICIPANTS AND METHODS: A comparative cross-sectional study among 75 working boys in small industrial workshops in Arab Gohaina village in Qaliuobia governorate and 75 students of the same residence was conducted. All children were interviewed and were subjected to physical examination. Their BMI and hemoglobin were measured, and stool samples were examined for parasites. RESULTS: Only 11 and 15% of the workers working children eat vegetables and fruits on daily basis compared with 25 and 49% of students respectively (P<0.001). Mean BMI of the working group was 21.62+/-2.56 compared with 23.29+/-3.09 among the students. Students showed more frequency of obesity and overweight than the working group (13.33 and 29.33% compared with 2.67 and 20%, respectively, P=0.009). The hemoglobin level of working children (10.27+/-0.53 g/dl) was less than that of students (11.31+/-0.75 g/dl, P<0.001). The frequency of having parasitic infestations among working children was significantly higher than the students (P<0.001). CONCLUSION AND RECOMMENDATIONS: Labor was a factor that negatively affected the health of children. More working children in this village had anemia and parasitic infestations than nonworking ones. It is recommended to pay more attention to health problems among working children, with controlling child labor, especially in hazardous occupations and performing periodic medical examination to monitor their health and development. PMID- 26154837 TI - Historical cohort analysis of treatment patterns for patients with type 2 diabetes initiating metformin monotherapy. AB - OBJECTIVE: To describe treatment regimen changes of patients with type 2 diabetes mellitus (T2DM) initiating metformin monotherapy, and assess factors associated with those changes 12 months post-initiation. METHODS: Retrospective cohort analysis of medical, pharmacy and laboratory claims of 17,527 Medicare Advantage (MAPD) Humana members aged 18-89, who had >=1 medical claim with primary diagnosis or >=2 medical claims with secondary diagnosis of T2DM (ICD-9-CM code 250.x0 or 250.x2) who filled an initial prescription for metformin (GPI code 2725) between 1 January 2008 and 30 September 2011. The main outcome measure was change in metformin monotherapy during the 12 months following initiation. Factors associated with treatment changes during follow-up were examined using Cox proportional hazards regression models. RESULTS: Fifty-nine percent of patients (mean age 69.6 years) remained on metformin monotherapy with no changes. Discontinuation was the most common treatment change (33%), followed by addition (5%), and switching (2%) to other antidiabetics. Of patients who discontinued treatment (median time to discontinuation = 90 days), 61% did not reinitiate any diabetic treatment during the follow-up period. Among patients who added or switched to other antidiabetics, sulfonylureas were the most common addition or replacement agent. Predictors of discontinuation were being female, Black or Hispanic, low-income subsidy eligible, having higher initial out-of-pocket metformin costs, or a diagnosis of depression. Discontinuation was less likely during follow-up if patients had higher pre-index pill burdens or records of a pre-index A1C screening test. A higher risk of discontinuation was observed for patients with low baseline A1C. One study limitation was that exact discontinuation dates could not be determined using claims. CONCLUSIONS: The findings suggest that gender, race, ethnicity, depression, and low income status were contributory factors to metformin discontinuation. More intensive monitoring and treatment adjustments may be warranted for patients newly initiated on metformin. This could ultimately improve morbidity, mortality, and costs associated with poor glycemic control. PMID- 26154838 TI - Theory for electric dipole superconductivity with an application for bilayer excitons. AB - Exciton superfluid is a macroscopic quantum phenomenon in which large quantities of excitons undergo the Bose-Einstein condensation. Recently, exciton superfluid has been widely studied in various bilayer systems. However, experimental measurements only provide indirect evidence for the existence of exciton superfluid. In this article, by viewing the exciton in a bilayer system as an electric dipole, we derive the London-type and Ginzburg-Landau-type equations for the electric dipole superconductors. By using these equations, we discover the Meissner-type effect and the electric dipole current Josephson effect. These effects can provide direct evidence for the formation of the exciton superfluid state in bilayer systems and pave new ways to drive an electric dipole current. PMID- 26154836 TI - Rate-Determining Attack on Substrate Precedes Rieske Cluster Oxidation during Cis Dihydroxylation by Benzoate Dioxygenase. AB - Rieske dearomatizing dioxygenases utilize a Rieske iron-sulfur cluster and a mononuclear Fe(II) located 15 A across a subunit boundary to catalyze O2 dependent formation of cis-dihydrodiol products from aromatic substrates. During catalysis, O2 binds to the Fe(II) while the substrate binds nearby. Single turnover reactions have shown that one electron from each metal center is required for catalysis. This finding suggested that the reactive intermediate is Fe(III)-(H)peroxo or HO-Fe(V)?O formed by O-O bond scission. Surprisingly, several kinetic phases were observed during the single-turnover Rieske cluster oxidation. Here, the Rieske cluster oxidation and product formation steps of a single turnover of benzoate 1,2-dioxygenase are investigated using benzoate and three fluorinated analogues. It is shown that the rate constant for product formation correlates with the reciprocal relaxation time of only the fastest kinetic phase (RRT-1) for each substrate, suggesting that the slower phases are not mechanistically relevant. RRT-1 is strongly dependent on substrate type, suggesting a role for substrate in electron transfer from the Rieske cluster to the mononuclear iron site. This insight, together with the substrate and O2 concentration dependencies of RRT-1, indicates that a reactive species is formed after substrate and O2 binding but before electron transfer from the Rieske cluster. Computational studies show that RRT-1 is correlated with the electron density at the substrate carbon closest to the Fe(II), consistent with initial electrophilic attack by an Fe(III)-superoxo intermediate. The resulting Fe(III) peroxo-aryl radical species would then readily accept an electron from the Rieske cluster to complete the cis-dihydroxylation reaction. PMID- 26154839 TI - Involutional entropion: risk factors and surgical remedies. AB - PURPOSE OF REVIEW: To review current surgical practices for the repair of lower eyelid involutional entropion with a focus on recent studies. RECENT FINDINGS: A shorter axial length, which may be interrelated with exophthalmometry, correlates with involutional entropion. Although it is known Asian eyelids more frequently develop involutional entropion, there is greater awareness of customized surgical approaches. Minimally invasive techniques for strengthening the action of lower eyelid retractors, such as everting sutures and transconjunctival approaches, continue to be refined and studied. Such surgery is efficacious in patients who do not have horizontal laxity. However, there is consistent evidence that in the presence of laxity the recurrence rate is higher if the eyelid is not horizontally tightened. SUMMARY: By knowing of the demographics and factors associated with involutional entropion, clinicians can have better understanding of the condition and the patients most at risk. There is not sufficient evidence to determine whether a short axial length is an independent-risk factor for entropion. Advances in surgical technique have led to continued interest in minimally invasive approaches. Precision in addressing individual patients' underlying anatomic abnormalities is important. PMID- 26154841 TI - A top-down methodology for ultrafast tuning of nanosized zeolites. AB - We herein present a top-down methodology to prepare nanosized zeolites with tunable size by combining post-synthesis milling and fast recrystallization of several minutes (10 min for SSZ-13 and 5 min for AlPO4-5). A continuous-flow recrystallization process is demonstrated to further enhance the overall product efficiency. PMID- 26154842 TI - STRAIN ELASTOGRAPHY USING DOBUTAMINE-INDUCED CAROTID ARTERY PULSATION IN CANINE THYROID GLAND. AB - Thyroid disease is common in dogs and conventional ultrasonography is a standard diagnostic test for diagnosis and treatment planning. Strain elastography can provide additional information about tissue stiffness noninvasively after applying external or internal compression. However, natural carotid artery pulsations in the canine thyroid gland are too weak to maintain sufficient internal compression force. The objective of the present study was to describe the feasibility of strain elastography for evaluating the canine thyroid gland and the repeatability of dobutamine-induced carotid artery pulsation as an internal compression method. In seven healthy Beagle dogs, strain on each thyroid lobe was induced by external compression using the ultrasound probe and internal compression using carotid artery pulsation after dobutamine infusion. The thyroid appeared homogeneously green and the subcutaneous fat superficial to the thyroid lobe appeared blue. Strain values and strain ratios did not differ among dogs or between the left and right lobes. Interobserver repeatability was excellent for both compression methods. Intraobserver repeatability of the strain ratio measured using the carotid artery pulsation method (intraclass coefficient correlation = 0.933) was higher than that measured using the external compression method (0.760). Mean strain values of thyroid lobes for the external compression method (142.93 +/- 6.67) differed from the internal method (147.31 +/- 8.24; P < 0.05). Strain ratios between the two methods did not differ. Strain elastography was feasible for estimating thyroid stiffness in dogs. Carotid artery pulsation induced by dobutamine infusion can be used for canine thyroid strain elastography with excellent repeatability. PMID- 26154843 TI - Difference in Tinnitus Treatment Outcome According to the Pulse Number of Repetitive Transcranial Magnetic Stimulation. AB - OBJECTIVE: We aimed to compare the treatment result between 6,000 and 12,000 pulses of low-frequency repetitive transcranial magnetic stimulation (rTMS) and to evaluate the correct location of rTMS in Korean brains compared with that of Caucasians. STUDY DESIGN: Controlled trial. SETTING: Tertiary referral center. PATIENTS: Fourteen patients with chronic essential tinnitus were treated with rTMS on the left auditory cortex (AC) and prefrontal cortex (FC). AC targets were determined using the 10-20 electroencephalographic (EEG) method proposed by Langguth in 2006. Six patients received a total of 6,000 pulses rTMS (AC, 1,000; FC, 1,000; 3-d course; Group 1), and eight patients were given 12,000 pulses (AC, 2,000; FC, 1,000; 4-d course; Group 2). MAIN OUTCOME MEASURES: Treatment results were assessed with pretreatment and posttreatment Tinnitus Handicap Inventory (THI) and self-rating Visual Analog Scale (VAS) of awareness, loudness, annoyance, and effect on daily life of tinnitus at 1, 2, 4, 8, and 12 weeks after treatment. Using the individual subject's magnetic resonance image and Neuronavigation System, the location of primary AC was determined and compared with that of the 10-20 method in four patients. RESULTS: There was no improvement of THI and VAS in Group 1. On the contrary, a substantial decrease of THI scores and VAS scores for awareness, loudness, and effect on daily life was observed in Group 2. CONCLUSION: Despite the small number of patients, a beneficial effect of rTMS on tinnitus suppression was found in the 12,000-pulse treatment group, whereas no effect was found in the 6,000-pulse treatment group. rTMS localization based on the 10-20 EEG method seems to be valid even in Koreans with a shorter anteroposterior skull diameter. PMID- 26154844 TI - Hearing Impairment in Children and Adults With Acquired Middle Ear Cholesteatoma: Audiometric Comparison of 385 Ears. AB - OBJECTIVE: Evaluate hearing impairment in acquired middle ear cholesteatoma and investigate audiometric differences between children and adults. STUDY DESIGN: Cross-sectional comparative study. SETTING: Tertiary hospital. PATIENTS: Three hundred twenty-three consecutive patients diagnosed as having acquired middle ear cholesteatoma in at least one ear (385 ears) between August 2000 and March 2013 and no surgical history (mean [standard deviation {SD}] age, 32.8 [19.4] yr; 54.3% men and 34.8% children). INTERVENTION: Pure-tone audiometry. MAIN OUTCOME MEASURES: Air-conduction (AC) and bone conduction (BC) thresholds and air-bone gaps (ABGs) measured at the pure-tone average (PTA) and individual frequencies. RESULTS: The mean (SD) AC and BC thresholds at the PTA were 46.8 (22.7) and 17.7 (17.5) dB, respectively. The mean (SD) ABG at the PTA was 29.6 (13.4) dB, and that at 500 Hz was significantly greater than the ABGs at the other frequencies. Only 3.6% of the ears had profound hearing loss, without a significant difference between children and adults. The AC and BC thresholds were significantly greater in adults at all the frequencies (p <= 0.05), but the ABGs were not significantly different between the age groups. CONCLUSION: Acquired middle ear cholesteatoma is associated with significant hearing impairment, although profound hearing loss is rare. Adults have greater AC and BC thresholds than those in children but similar ABGs to children. PMID- 26154845 TI - Re: "A note on unmasking" (Letter commenting on: J Clin Epidemiol. 2014;67:1059 69). PMID- 26154846 TI - CPU-12, a novel synthesized oxazolo[5,4-d]pyrimidine derivative, showed superior anti-angiogenic activity. AB - Angiogenesis is a crucial requirement for malignant tumor growth, progression and metastasis. Tumor-derived factors stimulate formation of new blood vessels which actively support tumor growth and spread. Various of drugs have been applied to inhibit tumor angiogenesis. CPU-12, 4-chloro-N-(4-((2-(4-methoxyphenyl)-5 methyloxazolo[5,4-d] pyrimidin-7-yl)amino)phenyl)benzamide, is a novel oxazolo[5,4-d]pyrimidine derivative that showed potent activity in inhibiting VEGF-induced angiogenesis in vitro and ex-vivo. In cell toxicity experiments, CPU 12 significantly inhibited the human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner with a low IC50 value at 9.30 +/- 1.24 MUM. In vitro, CPU-12 remarkably inhibited HUVEC's migration, chemotactic invasion and capillary-like tube formation in a dose-dependent manner. In ex vivo, CPU-12 effectively inhibited new microvessels sprouting from the rat aortic ring. In addition, the downstream signalings of vascular endothelial growth factor receptor-2 (VEGFR-2), including the phosphorylation of PI3K, ERK1/2 and p38 MAPK, were effectively down-regulated by CPU-12. These evidences suggested that angiogenic response via the induction of VEGFR through distinct signal transduction pathways regulating proliferation, migration and tube formation of endothelial cells was significantly inhibited by the novel small molecule compound CPU-12 in vitro and ex-vivo. In conclusion, CPU-12 showed superior anti angiogenic activity in vitro. PMID- 26154847 TI - Complex formation and functional interaction between adenosine A1 receptor and type-1 metabotropic glutamate receptor. AB - The adenosine A1 receptor (A1R) is a G protein-coupled receptor (GPCR) for adenosine, a ubiquitous neuromodulator, and thus regulates neuronal excitability, as well as arousal and sensitivity to pain. In addition, we have previously described a new mode of action for A1R: in cerebellar Purkinje cells, its activation attenuates neuronal responses to glutamate, as mediated by the type-1 metabotropic glutamate receptor (mGluR1). mGluR1 is also a GPCR, and elicits such responses as long-term depression of the postsynaptic response to glutamate, a cellular basis for cerebellar motor learning. Here, we explore in greater detail the interaction between A1R and mGluR1 using non-neuronal cells. Co immunoprecipitation and Forster resonance energy transfer (FRET) analysis reveal that A1R and mGluR1 form a complex. Furthermore, we found that mGluR1 activation inhibits A1R signaling, as measured by changes in intracellular cAMP. These findings demonstrate that A1R and mGluR1 have the intrinsic ability to form a heteromeric complex and mutually modulate signaling. This interaction may represent a new form of intriguing GPCR-mediated cellular responses. PMID- 26154848 TI - Plumbagin inhibits growth of gliomas in vivo via suppression of FOXM1 expression. AB - Plumbagin is a natural compound that is isolated from the root of the medicinal plant Plumbago zeylanica L. Based on a previous in vitro study performed by our group, which demonstrated the effectiveness of plumbagin against glioma cells, we further ascertained whether plumbagin exhibits the same effectiveness against glioma cell xenografts in nude mice. Our results revealed that tumor volume was reduced by 54.48% in the plumbagin-treated group compared with the controls. Furthermore, there were no obvious signs of toxicity as assessed by the organ sizes and cell morphologies of the mice that were treated with plumbagin. Immunofluorescence assays further revealed that plumbagin significantly inhibited glioma cell proliferation and induced cell apoptosis. Importantly, we also determined that the expressions of FOXM1 and its downstream target effectors, including cyclin D1 and Cdc25B, were down-regulated in the treated group, while the expressions of p21 and p27 were increased; the latter findings corroborate the results of our previous in vitro study. Taken together, these findings indicate that plumbagin may be a natural downregulator of FOXM1 with potential therapeutic effectiveness for the treatment of gliomas. PMID- 26154849 TI - Electron Injection from Copper Diimine Sensitizers into TiO2: Structural Effects and Their Implications for Solar Energy Conversion Devices. AB - Copper(I) diimine complexes have emerged as low cost replacements for ruthenium complexes as light sensitizers and electron donors, but their shorter metal-to ligand-charge-transfer (MLCT) states lifetimes and lability of transient Cu(II) species impede their intended functions. Two carboxylated Cu(I) bis-2,9 diphenylphenanthroline (dpp) complexes [Cu(I)(dpp-O(CH2CH2O)5)(dpp-(COOH)2)](+) and [Cu(I)(dpp-O(CH2CH2O)5)(dpp-(Phi-COOH)2)](+) (Phi = tolyl) with different linker lengths were synthesized in which the MLCT-state solvent quenching pathways are effectively blocked, the lifetime of the singlet MLCT state is prolonged, and the transient Cu(II) ligands are stabilized. Aiming at understanding the mechanisms of structural influence to the interfacial charge transfer in the dye-sensitized solar cell mimics, electronic and geometric structures as well as dynamics for the MLCT state of these complexes and their hybrid with TiO2 nanoparticles were investigated using optical transient spectroscopy, X-ray transient absorption spectroscopy, time-dependent density functional theory, and quantum dynamics simulations. The combined results show that these complexes exhibit strong absorption throughout the visible spectrum due to the severely flattened ground state, and a long-lived charge-separated Cu(II) has been achieved via ultrafast electron injection (<300 fs) from the (1)MLCT state into TiO2 nanoparticles. The results also indicate that the TiO2 phen distance in these systems does not have significant effect on the efficiency of the interfacial electron-transfer process. The mechanisms for electron transfer in these systems are discussed and used to develop new strategies in optimizing copper(I) diimine complexes in solar energy conversion devices. PMID- 26154851 TI - Effects of two contraceptives containing drospirenone on blood pressure in normotensive women: a randomized-controlled trial. AB - OBJECTIVE: Drospirenone (DRSP) is a progestogen derived from spironolactone with antimineralocorticoid action that seems to exert a favorable effect on blood pressure (BP); however, when associated with ethinylestradiol (EE), this effect does not seem to occur. This study aimed to assess possible differences in BP associated with the use of combined oral contraceptives containing DRSP with different doses of EE. MATERIALS AND METHODS: This open-label parallel-group randomized clinical trial involved women randomized to use either 30 mcg of EE+DRSP (n=22) or 20 mcg of EE+DRSP (n=22). Daytime, nighttime, and 24-h BP were evaluated by ambulatory blood pressure monitoring at the beginning of the trial and 6 months after drug therapy. RESULTS: The groups were similar in terms of demographic characteristics. The mean 24-h systolic blood pressure and diastolic blood pressure (DBP) were similar between the groups before and after treatment (P>0.05). With respect to day and nighttime systolic blood pressure and DBP, no statistically significant difference was observed in BP values between the two groups either before or after treatment, except for the daytime DBP in the 30EE+DRSP group. In this group, a decrease of 2 mmHg (3%) in daytime DBP was observed after 6 months of drug therapy (P=0.04). CONCLUSION: There was no difference in BP associated with the use of combined oral contraceptives containing DRSP irrespective of the EE dose used. PMID- 26154852 TI - Cuff inflations do not affect night-time blood pressure: comparison of 24 h ambulatory blood pressure measured by a cuff and a tonometric device in type 2 diabetes. AB - Discomfort related to cuff inflation may bias 24 h ambulatory blood pressure (BP) measurements, especially during night-time. We accessed the impact of cuff inflations by comparing 24 h BP recorded with a cuff-less tonometric wrist device and an upper-arm oscillometric cuff device. Fifty-three participants with type 2 diabetes were assigned randomly to four 24-h BP recordings with a cuff (TM2430: visit 1 or 2, and 4) and a tonometric device (BPro: visit 1 or 2, 3, and 4). The mean 24 h systolic BP was significantly higher when measured with the cuff versus the tonometric device (141.6+/-14.6 vs. 128.3+/-14.6 mmHg, P<=0.01), as was nocturnal BP (6.7+/-5.3 vs. 10.3+/-7.6%, P=0.002). In conclusion, nocturnal BP decline was higher when measured with the cuff device, suggesting that cuff inflations did not increase night-time BP. Further evaluation of the tonometric device using the updated European Society of Hypertension International Protocol revision 2010 is recommended before applying it in daily clinical practice. PMID- 26154853 TI - The SOMNOtouch device as a novel method for measuring short-term blood pressure variability: a comparison with the Finometer. AB - BACKGROUND: Current noninvasive techniques to capture short-term blood pressure variability (BPV) have methodological and practical limitations. This study assessed the ability of a novel device, the SOMNOtouch, which derives continuous blood pressure (BP) measures from pulse transit time, to estimate BPV, compared with the widely used Finometer. METHODS: BP monitoring was performed simultaneously on the SOMNOtouch and Finometer devices in 16 healthy volunteers. Systolic and diastolic BPVs, defined as SD and coefficient of variation, were derived from measurements from each device for three predefined periods: 0-3, 7 10, and 0-10 min. RESULTS: Agreement in BPV indices from the two devices was assessed using the Bland-Altman technique. For all BPV parameters, over all measurement periods, broad scatter was observed on Bland-Altman plots. Bias (limits of agreement) for minutes 0-10: SD of systolic BP, -3.03 mmHg (-10.88 to +4.55), SD of diastolic BP -1.65 mmHg (-4.41 to +1.11). CONCLUSIONS: The poor agreement observed in BPV estimates between the devices may reflect the inability of the current pulse transit time method to sensitively detect changes in BP. Further investigation is needed before such methods can be reliably used to measure short-term BPV. PMID- 26154854 TI - Characteristics of self-measured home blood pressure in a Nigerian urban community: the NIPREGH study. AB - OBJECTIVE: We investigated the characteristics of self-measured home blood pressure (HBP) in a randomly selected population of Nigerians living in Abuja, Nigeria. METHODS: HBP was the average of 28 measurements comprising duplicate morning and evening readings obtained over a 7-day period by the participants using a semiautomated oscillometric device. Blood pressure measured five consecutive times by trained observers using mercury sphygmomanometer was averaged as the office blood pressure (OBP). RESULTS: Among the 337 participants included in the analysis, 46.6% were women and their mean age (SD) 40.3 (11.3). The mean, mean+2 SD and 95th percentile of HBP and OBP were 117/76, 147/96 and 145/93 mmHg and 114/73, 147/97 and 142/73 mmHg, respectively. The corresponding values in normotensive individuals were 113/73, 137/89 and 132/88 mmHg and 108/70, 130/88 and 128/84 mmHg. Morning HBPs were significantly higher than that of the evening, with a mean difference (confidence interval) of 1.8 mmHg (1.1-2.5 mmHg) and 1.9 mmHg (1.4-2.3 mmHg) for systolic and diastolic pressures, respectively (P<0.0001). There is a strong correlation between the office and home systolic (r=0.8, P<0.0001) and diastolic (r=0.7, P<0.0001) pressures. Overall, the HBP values were significantly higher than OBP, with a mean difference (confidence interval) of systolic/diastolic of 3.6 mmHg (2.5-4.6 mmHg)/2.3 mmHg (1.4-3.1 mmHg) (P<0.0001). The HBP/OBP difference was maintained in men and normotensive individuals, but in women and hypertensive participants, there was no significant difference between HBP and OBP. CONCLUSION: Our findings have shown that self-measured blood pressure is feasible and can be used to evaluate blood pressure outside the clinic environment among Nigerians. PMID- 26154855 TI - ANA Convention Reflects Growth in Gerontological Nursing. PMID- 26154856 TI - Contemporary Practice Patterns of Flexible Ureteroscopy for Treating Renal Stones: Results of a Worldwide Survey. AB - INTRODUCTION: Flexible ureteroscopy (fURS) is increasingly used in the treatment of renal stones. However, wide variations exist in technique, use, and indications. To better inform our knowledge about the contemporary state of fURS for treating renal stones, we conducted a survey of endourologists worldwide. METHODS: An anonymous online questionnaire assessing fURS treatment of renal stones, consisting of 36 items, was sent to members of the Endourology Society in October 2014. Responses were collected through the SurveyMonkey system over a 3 month period. RESULTS: Questionnaires were answered by 414 surgeons from 44 countries (response rate 20.7%). U.S. surgeons accounted for 34.4% of all respondents. fURS was routinely performed in 80.0% of institutions, with 40.0% of surgeons performing >100 cases/year. Respondents considered fURS to be first-line therapy for patients with renal stones <2 cm and lower pole calculi. A substantial minority (11.3%) preferred fURS as a primary treatment modality for renal stones >2 cm. Basket displacement for lower pole stones was routinely performed by 55.8%. Ureteral access sheaths (UAS) were preferred for every case by 58.3%. Respondents frequently utilized high-power lasers and dusting techniques. Criteria for determining stone-free rate were defined as zero fragments or residual fragment (RF) <1, <2, <3, and <4 mm by 30.9%, 8.9%, 31.5%, 15.8%, and 11.2% of respondents, respectively. CONCLUSION: The overwhelming majority of endourologists surveyed consider fURS as a first-line treatment modality for renal stones, especially those <2 cm. Use of UAS, high-power holmium lasers, and dusting technique has become popular among practitioners. When defining stone free after fURS, the majority of endourologists used a zero fragment or RF <2 mm definition. PMID- 26154857 TI - Novel drug target identification for the treatment of dementia using multi relational association mining. AB - Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia. PMID- 26154858 TI - An Association Study Between Gene Polymorphisms of Folic Acid Metabolism Enzymes and Biochemical and Hormonal Parameters in Acromegaly. AB - AIM: Folate metabolism is fundamental to several biological functions and required for cell replication, division, and survival. The mammalian folic acid cycle is highly complex and the enzymes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR), have crucial roles in this metabolic pathway. The common polymorphisms of the MTHFR (C677T and A1298C), MTRR (A66G), and MTR (A2756G) enzymes are well documented as folate deficiency-related disorders, but their roles have not been examined in acromegalic patients. The aim of this study was to compare the genotypic distribution of these gene polymorphisms between patients with acromegaly and controls and explore whether these polymorphisms were associated with biochemical and hormonal parameters in acromegaly. We examined 91 acromegaly patients and 112 healthy subjects who were compared in terms of age and gender. Blood specimens of the subjects were collected in tubes containing ethylenediaminetetraacetic acid. Genomic DNA was isolated from peripheral blood leukocytes and genotyping of the MTHFR (C677T and A1298C) gene polymorphisms was assessed by melting temperature analyses after real-time polymerase chain reaction (PCR), whereas MTRR A66G and MTR A2756G gene polymorphism analyses were performed by PCR/restriction fragment length polymorphism from the isolated DNA of the subjects. RESULTS: MTHFR-677TT genotype frequency was significantly higher in the acromegaly group than the control group (p=0.017), and a significant increase was found in fibrinogen (p=0.032) levels in 677TT-carrying acromegaly patients. MTRR-66AA genotype was significantly higher in the control group than the acromegaly group (p=0.004). Total cholesterol (p=0.048) and C-reactive protein (p=0.046) levels decreased significantly in 66AA genotypes. Although MTR 2756AG genotype frequency was not different between the control and acromegaly groups, 2756AG genotype-carrying individuals have higher left carotid intima media thickness levels within the patient group. CONCLUSION: Our results suggest that polymorphisms of the genes encoding the folic acid metabolism enzymes affect biochemical parameters in acromegaly and this may result in predispositions to some complications associated with folate metabolism and acromegaly. PMID- 26154859 TI - Spatial disparities of the willingness of the residents to pay for the wetland restoration of Taihu Lake and its integration into decision making: a case study on Wuxi, China. AB - Many wetland restoration projects (WRPs) have been conducted to restore the wetland ecosystem since a massive bloom of cyanobacteria in Taihu Lake in the summer of 2007. The willingness to pay (WTP) of residents for wetland restoration was expected to exhibit spatial disparities that were used for decision making. In this study, correlation analysis, binary logistic regression, and linear regression were used to assess 400 questionnaires collected through a contingent valuation survey. Results indicated that WTP amounts and the probability of positive WTP decrease as the distance from the wetlands increases. Knowledge of WRPs was the only factor that influences whether the respondents pay in the close distance (<3 km) and medium distance districts (>3 and <10 km), whereas in the remote distance district (>10 km), gender and income also affected WTP decision aside from the knowledge of WRPs. In terms of WTP amounts, income was the determining factor in the three districts, whereas age was a factor in the medium distance area. Results also showed that the growth rate of the water price should vary according to the distance of the area from the location of the WRPs. The water price was recommended to be increased by US$ 0.522/ton, 0.520/ton, and 0.509/ton in the close, medium, and remote distance districts, respectively. PMID- 26154860 TI - Effects of logging activities on ecological water quality indicators in the Berasau River, Johor, Malaysia. AB - Influence of deforestation on biodiversity of aquatic organisms was investigated in a stream in the Ulu Sedili Forest Reserve. The stream was monitored five (5) times from December 2011 until December 2012 with 2-month intervals. Sampling of benthic communities was carried out using rectangular dip net while water quality study using a YSI ProPlus meter and the rest were done in the laboratory. Physicochemical parameters and water quality index (WQI) calculation showed no significant difference among the investigated events. WQI classified the Berasau River between Class II (good) to III (moderate) of river water quality. In total, 603 individuals representing 25 taxa that were recorded with Decapods from genus Macrobrabchium were widely distributed. Several intolerant taxa, especially Ephemeroptera and Odonata, were also observed in this river. According to Pearson's correlation analysis, the richness and diversity indices were generally influenced by water quality parameters represented by WQI (P < 0.01). In conclusion, logging activities have strong attributes for variation in benthic macroinvertebrate assemblage. PMID- 26154861 TI - Improving skills development in residency using a deliberate-practice and learner centered model. AB - OBJECTIVES/HYPOTHESIS: Work-hour restrictions, increased workload, and subjective assessment of competency are major threats to the efficacy of the traditional apprenticeship model of surgical training in modern surgical practice. In response, medical educators are developing time- and resource-efficient competency-based models of surgical training. The purpose of our project was to develop, implement, and measure the outcomes of such objective and structured programs in otolaryngology. We also investigated factors affecting the learning curve, especially deliberate practice, formative feedback, and learners' autonomy. STUDY DESIGN: Prospective, longitudinal study. METHODS: To measure the surgical skills of residents, we first developed and tested objective tools for otolaryngology procedures. Based on these instruments, we identified milestones of the procedures. Training on a virtual-reality simulator was validated to shorten the learning curve. We also studied a learner-centered approach of training, factors affecting the learning curve, and barriers to a competency based model. RESULTS: The objective tools were found to be a feasible, reliable, and valid opportunity for measuring competency in both the laboratory and operating room. With the formative assessment from these tools, residents had a remediation target to be achieved by deliberate practice. The milestones helped identify the threshold of competency, and deliberate practice on the simulator gave an opportunity for improving skills. The learner-centered approach allowed flexibility and personalized learning by shifting the responsibility of the learning process to the learners. CONCLUSION: The competency-based model of residency, based on the principles of deliberate practice and a learner-centered approach, is a feasible model of residency training that allows development of competent surgeons and hence improves patient outcomes. Despite these advantages, challenges to this model require a concerted effort to overcome and fully implement these principles of training beyond just technical skills, ultimately creating well-rounded medical professionals and leaders in the surgical field. LEVEL OF EVIDENCE: N/A. Laryngoscope, 125:S1-S14, 2015. PMID- 26154862 TI - Endeavour to simplify the frustrated concept of protein-ammonium family ionic liquid interactions. AB - The large amount of attention earned by ionic liquids (ILs) in the various physical and chemical sciences has been attributed to their unique, designer nature. In the past few years, the role of ILs in protein folding/unfolding has been rapidly growing. In light of the increasing importance of ILs, it is desirable to systematize the ion effects on protein properties such as structure stability, activity and enantioselectivity. Various studies available in the literature show ILs as a potential solvent medium for many enzymatic reactions, as well as in various protein folding/unfolding studies. Various reviews by many researchers focus on the synthesis, application and general properties of the ILs, however a review focussing on the effect of various ILs on the activity, structure and stability of proteins is still missing. Also, according to the best of our knowledge there is no single review available throughout the literature that focuses on the effect of the same family of ILs on different proteins. Therefore, it is a priority to obtain complete knowledge of the biomolecules, particularly amino acids (AAs) and proteins in a particular IL family. The focus of the present perspective is to investigate the performance of a list of proteins and protein model compounds in the presence of ammonium-based ILs. This perspective presents a survey of all the key developments from the available reports and also our past and present experience related to proteins and ammonium based ILs. Additionally, we have tried to put the available information in chronological order in most of the cases. The use of ammonium family ILs as a co solvent for various proteins model compounds and proteins has been outlined. This perspective can act as a barometer for reckoning the various advancements made in this field and can also galvanize further investigation of various untouched aspects of this research area. PMID- 26154863 TI - Assessing medical student empathy in a family medicine clinical test: validity of the CARE measure. AB - INTRODUCTION: The Consultation and Relational Empathy (CARE) measure developed and validated in primary care settings and used for general practitioner appraisal is a 10-item instrument used by patients to assess doctors' empathy. The aim of this study is to investigate the validity of the CARE measure in assessing medical students' empathy during a formative family medicine clinical test. METHOD: All 158 final-year medical students were assessed by trained simulated patients (SPs) - who completed the CARE measure, the Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE), and a global rating score to assess students' empathy and history-taking ability. RESULTS: Exploratory and confirmatory factor analysis identified a unidimensional structure. The CARE measure strongly correlated with both convergent measures: global rating (rho=0.79 and <0.001) and JSPPPE (rho=0.77 and <0.001) and weakly correlated with the divergent measure: history-taking score (rho=0.28 and <0.001). Internal consistency was excellent (Cronbach's alpha=0.94). CONCLUSION: The CARE measure had strong construct and internal reliability in a formative, undergraduate family medicine examination. Its role in higher stakes examinations and other educational settings should be explored. PMID- 26154864 TI - Impact of tailored feedback in assessment of communication skills for medical students. AB - BACKGROUND: Finding out the effective ways of teaching and assessing communication skills remain a challenging part of medication education. This study aims at exploring the usefulness and effectiveness of having additional feedback using qualitative analysis in assessment of communication skills in undergraduate medical training. We also determined the possibilities of using qualitative analysis in developing tailored strategies for improvement in communication skills training. METHODS: This study was carried out on medical students (n=87) undergoing their final year clinical performance examination on communication skills using standardized patient by video-recording and transcribing their performances. Video-recordings of 26 students were randomly selected for qualitative analysis, and additional feedback was provided. We assessed the level of acceptance of communication skills scores between the study and nonstudy group and within the study group, before and after receiving feedback based on qualitative analysis. RESULTS: There was a statistically significant increase in the level of acceptance of feedback after delivering additional feedback using qualitative analysis, where the percentage of agreement with feedback increased from 15.4 to 80.8% (p<0.001). CONCLUSIONS: Incorporating feedback based on qualitative analysis for communication skills assessment gives essential information for medical students to learn and self-reflect, which could potentially lead to improved communication skills. As evident from our study, feedback becomes more meaningful and effective with additional feedback using qualitative analysis. PMID- 26154865 TI - The bidirectional association between reduced cerebral blood flow and brain atrophy in the general population. AB - The question remains whether reduced cerebral blood flow (CBF) leads to brain atrophy or vice versa. We studied the longitudinal relation between CBF and brain volume in a community-dwelling population. In the Rotterdam Study, 3011 participants (mean age 59.6 years (s.d. 8.0)) underwent repeat brain magnetic resonance imaging to quantify brain volume and CBF at two time points. Adjusted linear regression models were used to investigate the bidirectional relation between CBF and brain volume. We found that smaller brain volume at baseline was associated with a steeper decrease in CBF in the whole population (standardized change per s.d. increase of total brain volume (TBV)=0.296 (95% confidence interval (CI) 0.200; 0.393)). Only in persons aged ?65 years, a lower CBF at baseline was associated with steeper decline of TBV (standardized change per s.d. increase of CBF=0.003 (95% CI -0.004; 0.010) in the whole population and 0.020 (95% CI 0.004; 0.036) in those aged ?65 years of age). Our results indicate that brain atrophy causes CBF to decrease over time, rather than vice versa. Only in persons aged >65 years of age did we find lower CBF to also relate to brain atrophy. PMID- 26154866 TI - Decreased microvascular cerebral blood flow assessed by diffuse correlation spectroscopy after repetitive concussions in mice. AB - Repetitive concussions are associated with long-term cognitive dysfunction that can be attenuated by increasing the time intervals between concussions; however, biomarkers of the safest rest interval between injuries remain undefined. We hypothesize that deranged cerebral blood flow (CBF) is a candidate biomarker for vulnerability to repetitive concussions. Using a mouse model of human concussion, we examined the effect of single and repetitive concussions on cognition and on an index of CBF (CBFi) measured with diffuse correlation spectroscopy. After a single mild concussion, CBFi was reduced by 35+/-4% at 4 hours (P<0.01 versus baseline) and returned to preinjury levels by 24 hours. After five concussions spaced 1 day apart, CBFi was also reduced from preinjury levels 4 hours after each concussion but had returned to preinjury levels by 72 hours after the final concussion. Interestingly, in this repetitive concussion model, lower CBFi values measured both preinjury and 4 hours after the third concussion were associated with worse performance on the Morris water maze assessed 72 hours after the final concussion. We conclude that low CBFi measured either before or early on in the evolution of injury caused by repetitive concussions could be a useful predictor of cognitive outcome. PMID- 26154868 TI - Leaving the black box approach: individualized prediction of recanalization benefit by advanced imaging in acute stroke. PMID- 26154867 TI - Multivariate dynamic prediction of ischemic infarction and tissue salvage as a function of time and degree of recanalization. AB - Benefit of endovascular recanalization beyond established treatment time windows likely exists in select stroke patients. However, there is currently no imaging model that predicts infarction adjusting for elapsed time between the pathologic snapshot of admission imaging until endovascular recanalization. We trained and cross validated a multivariate generalized linear model (GLM) that uses computer tomography perfusion and clinical data to quantify patient-specific dynamic change of tissue infarction depending on degree and time of recanalization. Multicenter data of 161 patients with proximal anterior circulation occlusion undergoing endovascular therapy were included. Multivariate voxelwise infarct probability was calculated within the GLM. The effect of increasing time to treatment and degree of recanalization on voxelwise infarction was calculated in each patient. Tissue benefit of successful relative to unsuccessful recanalization was shown up to 15 hours after onset in individual patients and decreased nonlinearly with time. On average, the relative reduction of infarct volume at the treatment interval of 5 hours was 53% and this salvage effect decreased by 5% units per hour to <5% after 10 additional hours to treatment. Treatment time-adjusted multivariate prediction of infarction by perfusion and clinical status may identify patients who benefit from extended time to recanalization therapy. PMID- 26154871 TI - Some Thoughts on the Nursing of Older People. PMID- 26154870 TI - Mechanism of brain targeting by dexibuprofen prodrugs modified with ethanolamine related structures. AB - The first molecular insights into how prodrugs modified with ethanolamine-related structures target the brain were generated using an in vitro BBB model and in situ perfusion technique. Prodrugs were delivered safely and efficiently to the brain through tight interaction with the anionic membrane of brain capillary endothelial cells, observed as a shift in zeta potential, followed by uptake into the cells. Prodrugs III and IV carrying primary and secondary amine modifications appeared to enter the brain via energy-independent passive diffusion. In contrast, besides the passive diffusion, prodrugs I and II carrying tertiary amine modifications also appeared to enter via an active process that was energy and pH dependent but was independent of sodium or membrane potential. This active process involved, at least in part, the pyrilamine-sensitive H(+)/OC antiporter, for which the N,N-diethyl-based compound II showed a much lower affinity than the N,N-dimethyl-based compound I, likely due to steric hindrance. These new insights into brain-targeting mechanisms may help guide efforts to design new prodrugs. PMID- 26154872 TI - Mixed Hemi/Ad-Micelle Sodium Dodecyl Sulfate-Coated Magnetic Iron Oxide Nanoparticles for the Efficient Removal and Trace Determination of Rhodamine-B and Rhodamine-6G. AB - Mixed hemi/ad-micelle sodium dodecyl sulfate (SDS)-coated magnetic iron oxide nanoparticles (MHAMS-MIONPs) were used as an efficient adsorbent for both removal and preconcentration of two important carcinogenic xanthine dyes named rhodamine B (RB) and rhodamine-6G (RG). To gain insight in the configuration of SDS molecules on the surface of MIONPs, zeta potential measurements were performed in different [SDS]/[MIONP] ratios. Zeta potential data indicated that mixed hemi/ad micelle MHAM was formed in [SDS]/[MIONP] ratios over the range of 1.1 to 7.3. Parameters affecting the adsorption of dyes were optimized as removal efficiency by one variable at-a-time and response surface methodology; the obtained removal efficiencies were ~100%. Adsorption kinetic and equilibrium studies, under the optimum condition (pH = 2; amount of MIONPs = 87.15 mg; [SDS]/[MIONP] ratio = 2.9), showed that adsorption of both dyes are based on the pseudo-second-order and the Langmuir isotherm models, respectively. The maximum adsorption capacities for RB and RG were 385 and 323 mg g(-1), respectively. MHAMS-MIONPs were also applied for extraction of RB and RG. Under optimum conditions (pH = 2; amount of damped MHAMS-MIONPs = 90 mg; eluent solvent volume = 2.6 mL of 3% acetic acid in acetonitrile), extraction recoveries for 0.5 mg L(-1) of RB and RG were 98% and 99%, with preconcentration factors of 327 and 330, respectively. Limit of detection obtained for rhodamine dyes were <0.7 ng mL(-1). Finally, MHAMS-MIONPs were successfully applied for both removal and trace determination of RB and RG in environmental and wastewater samples. PMID- 26154869 TI - S100B inhibition reduces behavioral and pathologic changes in experimental traumatic brain injury. AB - Neuroinflammation following traumatic brain injury (TBI) is increasingly recognized to contribute to chronic tissue loss and neurologic dysfunction. Circulating levels of S100B increase after TBI and have been used as a biomarker. S100B is produced by activated astrocytes and can promote microglial activation; signaling by S100B through interaction with the multiligand advanced glycation end product-specific receptor (AGER) has been implicated in brain injury and microglial activation during chronic neurodegeneration. We examined the effects of S100B inhibition in a controlled cortical impact model, using S100B knockout mice or administration of neutralizing S100B antibody. Both interventions significantly reduced TBI-induced lesion volume, improved retention memory function, and attenuated microglial activation. The neutralizing antibody also significantly reduced sensorimotor deficits and improved neuronal survival in the cortex. However, S100B did not alter microglial activation in BV2 cells or primary microglial cultures stimulated by lipopolysaccharide or interferon gamma. Further, proximity ligation assays did not support direct interaction in the brain between S100B and AGER following TBI. Future studies are needed to elucidate specific pathways underlying S100B-mediated neuroinflammatory actions after TBI. Our results strongly implicate S100B in TBI-induced neuroinflammation, cell loss, and neurologic dysfunction, thereby indicating that it is a potential therapeutic target for TBI. PMID- 26154873 TI - Short communication: mucocutaneous leishmaniasis in HIV-related immune reconstitution syndrome. AB - Immune reconstitution inflammatory syndrome (IRIS) is an immuno-pathologic reaction to quiescent opportunistic microbial pathogens upon restoration of underlying immune defects. Here we report a Honduran patient with HIV/AIDS who developed a facial rash worsening on antiretroviral therapy and increasing CD4 count. Culture and PCR analysis from the skin biopsy identified Leishmania panamensis, which was effectively treated with long-term liposomal amphotericin B. This is the first report of mucocutaneous leishmaniasis (MCL)-associated IRIS due to L. panamensis. PMID- 26154874 TI - MRI assessment of excess cardiac iron in thalassemia major: When to initiate? AB - BACKGROUND: To determine optimal initial age of cardiac iron screening with magnetic resonance imaging (MRI) T2* in patients with thalassemia major (TM). METHODS: We retrospectively reviewed black blood cardiac T2* assessments from 102 TM patients from the ages of 3 to 32 years. Cases of patients under and above 7 years old with detectable cardiac iron overload were analyzed separately. Associations between cardiac T2* and various factors, such as serum ferritin (SF), patient age and hepatic T2*, were assessed using either scatterplots or regression. Images were evaluated by two independent radiologists. RESULTS: With a T2* cut-off value of 20 ms, no patient under 5 years old showed cardiac iron overload. Three of 19 (15.8%) patients under 7 years of age had a cardiac T2* <= 20 ms (5.5 to 7 years) but none had <=10 ms, while 35 of 83 (42.2%) patients above 7 years old had a cardiac T2* <= 20 ms (8 to 32 years) and 18 of them <=10 ms. Cardiac T2* correlated weakly with serum ferritin and liver T2* (r = -0.39 and 0.41, respectively, both P < 0.001), but not with patient age (P > 0.05). CONCLUSION: Cardiac iron overload can occur in young TM patients, even as young as 5.5 years old. Assessment of cardiac iron with T2* might need to begin as early as 5 years old if suboptimal chelation therapy is administered. PMID- 26154875 TI - Olefin Preparation via Palladium-Catalyzed Oxidative De-Azotative and De Sulfitative Internal Cross-Coupling of Sulfonylhydrazones. AB - A novel reactivity of sulfonylhydrazones under Pd catalysis is described, where SO2 and N2 are formally extruded to afford the product of an apparent internal coupling reaction. The reaction is effective with both carbocyclic and heterocyclic aromatic precursors. PMID- 26154876 TI - Large increase in nest size linked to climate change: an indicator of life history, senescence and condition. AB - Many animals build extravagant nests that exceed the size required for successful reproduction. Large nests may signal the parenting ability of nest builders suggesting that nests may have a signaling function. In particular, many raptors build very large nests for their body size. We studied nest size in the goshawk Accipiter gentilis, which is a top predator throughout most of the Nearctic. Both males and females build nests, and males provision their females and offspring with food. Nest volume in the goshawk is almost three-fold larger than predicted from their body size. Nest size in the goshawk is highly variable and may reach more than 600 kg for a bird that weighs ca. 1 kg. While 8.5% of nests fell down, smaller nests fell down more often than large nests. There was a hump-shaped relationship between nest volume and female age, with a decline in nest volume late in life, as expected for senescence. Clutch size increased with nest volume. Nest volume increased during 1977-2014 in an accelerating fashion, linked to increasing spring temperature during April, when goshawks build and start reproduction. These findings are consistent with nest size being a reliable signal of parental ability, with large nest size signaling superior parenting ability and senescence, and also indicating climate warming. PMID- 26154877 TI - Budd-Chiari Syndrome in a Child With Leukocyte Adhesion Deficiency-A Rare Association. PMID- 26154878 TI - Aqueous acidities of primary benzenesulfonamides: Quantum chemical predictions based on density functional theory and SMD. AB - Aqueous pK(a) of selected primary benzenesulfonamides are predicted in a systematic manner using density functional theory methods and the SMD solvent model together with direct and proton exchange thermodynamic cycles. Some test calculations were also performed using high-level composite CBS-QB3 approach. The direct scheme generally does not yield a satisfactory agreement between calculated and measured acidities due to a severe overestimation of the Gibbs free energy changes of the gas-phase deprotonation reaction by the used exchange correlation functionals. The relative pK(a) values calculated using proton exchange method compare to experimental data very well in both qualitative and quantitative terms, with a mean absolute error of about 0.4 pK(a) units. To achieve this accuracy, we find it mandatory to perform geometry optimization of the neutral and anionic species in the gas and solution phases separately, because different conformations are stabilized in these two cases. We have attempted to evaluate the effect of the conformer-averaged free energies in the pK(a) predictions, and the general conclusion is that this procedure is highly too costly as compared with the very small improvement we have gained. PMID- 26154879 TI - Systematic review of the methodological quality of studies designed to create neonatal anthropometric charts. AB - Babies all over the world are assessed at birth using neonatal anthropometric charts as a matter of clinical routine. This systematic review evaluated the methodological quality of studies designed to create neonatal anthropometric charts and to highlight features in the charts that could affect clinical decision-making and comparisons between populations. The variety and quality of available charts could affect how newborns at risk are identified, together with the indications for treatment, especially nutritional interventions. CONCLUSION: The studies that generated the charts currently recommended for clinical use have major methodological limitations and international and regional comparisons are very difficult. PMID- 26154881 TI - RNA Oligomerization in Laboratory Analogues of Alkaline Hydrothermal Vent Systems. AB - Discovering pathways leading to long-chain RNA formation under feasible prebiotic conditions is an essential step toward demonstrating the viability of the RNA World hypothesis. Intensive research efforts have provided evidence of RNA oligomerization by using circular ribonucleotides, imidazole-activated ribonucleotides with montmorillonite catalyst, and ribonucleotides in the presence of lipids. Additionally, mineral surfaces such as borates, apatite, and calcite have been shown to catalyze the formation of small organic compounds from inorganic precursors (Cleaves, 2008 ), pointing to possible geological sites for the origins of life. Indeed, the catalytic properties of these particular minerals provide compelling evidence for alkaline hydrothermal vents as a potential site for the origins of life since, at these vents, large metal-rich chimney structures can form that have been shown to be energetically favorable to diverse forms of life. Here, we test the ability of iron- and sulfur-rich chimneys to support RNA oligomerization reactions using imidazole-activated and non-activated ribonucleotides. The chimneys were synthesized in the laboratory in aqueous "ocean" solutions under conditions consistent with current understanding of early Earth. Effects of elemental composition, pH, inclusion of catalytic montmorillonite clay, doping of chimneys with small organic compounds, and in situ ribonucleotide activation on RNA polymerization were investigated. These experiments, under certain conditions, showed successful dimerization by using unmodified ribonucleotides, with the generation of RNA oligomers up to 4 units in length when imidazole-activated ribonucleotides were used instead. Elemental analysis of the chimney precipitates and the reaction solutions showed that most of the metal cations that were determined were preferentially partitioned into the chimneys. PMID- 26154880 TI - Challenging obesity: Patient, provider, and expert perspectives on the roles of available and emerging nonsurgical therapies. AB - OBJECTIVE: Adult obesity is recognized as a chronic disease. According to principles of chronic disease management, healthcare professionals should work collaboratively with patients to determine appropriate therapeutic strategies that address overweight and obesity, specifically considering a patient's disease status in addition to their individual needs, preferences, and attitudes regarding treatment. A central role and responsibility of healthcare professionals in this process is to inform and educate patients about their treatment options. Although current recommendations for the management of adult obesity provide general guidance regarding safe and proper implementation of lifestyle, pharmacological, and surgical interventions, healthcare professionals need awareness of specific evidence-based information that supports individualized clinical application of these therapies. More specifically, healthcare professionals should be up-to-date on approaches that promote successful lifestyle management and be knowledgeable about newer weight loss pharmacotherapies, so they can offer patients with obesity a wide range of options to personalize their treatment. Accordingly, this educational activity has been developed to provide participants with the latest information on treatment recommendations and therapeutic advances in lifestyle intervention and pharmacotherapy for adult obesity management. DESIGN AND METHODS: This supplement is based on the content presented at a live CME symposium held in conjunction with ObesityWeek 2014. RESULTS: This supplement provides an expert summary of current treatment recommendations and recent advances in nonsurgical therapies for the management of adult obesity. Patient and provider perspectives on obesity management are highlighted in embedded video clips available via QR codes, and new evidence will be applied using clinically relevant case studies. CONCLUSIONS: This supplement provides a topical update of obesity management, including clinical practice examples, for healthcare professionals who treat or provide care for adults with obesity. PMID- 26154882 TI - Surgical site infection after primary hip and knee arthroplasty: a cohort study using a hospital database. AB - BACKGROUND: Hip or knee arthroplasty infection (HKAI) leads to heavy medical consequences even if rare. OBJECTIVE: To assess the routine use of a hospital discharge detection algorithm of prosthetic joint infection as a novel additional tool for surveillance. METHODS: A historic 5-year cohort study was built using a hospital database of people undergoing a first hip or knee arthroplasty in 1 French region (2.5 million inhabitants, 39 private and public hospitals): 32,678 patients with arthroplasty code plus corresponding prosthetic material code were tagged. HKAI occurrence was then tracked in the follow-up on the basis of a previously validated algorithm using International Statistical Classification of Disease, Tenth Revision, codes as well as the surgical procedures coded. HKAI density incidence was estimated during the follow-up (up to 4 years after surgery); risk factors were analyzed using Cox regression. RESULTS: A total of 604 HKAI patients were identified: 1-year HKAI incidence was1.31%, and density incidence was 2.2/100 person-years in hip and 2.5/100 person-years in knee. HKAI occurred within the first 30 days after surgery for 30% but more than 1 year after replacement for 29%. Patients aged 75 years or older, male, or having liver diseases, alcohol abuse, or ulcer sore had higher risk of infection. The inpatient case fatality in HKAI patients was 11.4%. CONCLUSIONS: The hospital database method used to measure occurrence and risk factors of prosthetic joint infection helped to survey HKAI and could optimize healthcare delivery. PMID- 26154883 TI - Nanosize titanium dioxide cause neuronal apoptosis: a potential linkage between nanoparticle exposure and neural disorder. AB - OBJECTIVES: Nanosize titanium dioxide is used in water and air decontamination and in numerous home appliances and products designed for direct human use. However, the impact of nanoparticle on biological system is not known to us. Therefore, it is our urgent and primary task to ascertain the information about safety and potential hazards of products derived from nanomaterial to the health of mankind. METHODS: We made use of MTT, bromodeoxyuridine (BrdU), and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays to testify the biological impact of nanosize TiO2 on olfactory bulb neurons cultured in vitro. RESULTS: In this article, we elucidate the cytotoxicity of titanium dioxide to olfactory bulb neurons on cellular and molecular level. We come to a conclusion that nanosize titanium dioxide causes neuronal apoptosis, and it also down-regulate the expression of olfactory marker protein (OMP) and tyrosine hydroxylase (TH). DISCUSSION: These results show that a relationship between nanoparticle exposure and pathogeny of neurodegenerative diseases may exist. PMID- 26154885 TI - Synthesis and Evaluation of New Podophyllotoxin Derivatives with in Vitro Anticancer Activity. AB - A series of novel podophyllotoxin derivatives were designed and synthesized. The cytotoxic activities of these compounds were tested against three tumor cell lines (HeLa, K562, and K562/A02). Most of the derivatives (IC50 = 1-20 MUM) were found to have stronger cell growth inhibitory activity than positive control etoposide. Among them, 4beta-N-[(E)-(5-((4-(4-nitrophenyl)-piperazin-1 yl)methyl)furan-2-yl)prop-2-en-1-amine]-4-desoxy-podophyllotoxin (9l) demonstrated significant inhibitory activity against HeLa, K562, and K562/A02 cell lines with IC50 values of 7.93, 6.42, 6.89 MUM, respectively. PMID- 26154886 TI - Quantification of Polyfunctional Thiols in Wine by HS-SPME-GC-MS Following Extractive Alkylation. AB - Analyses of key odorous polyfunctional volatile thiols in wines (3 mercaptohexanol (3-MH), 3-mercaptohexylacetate (3-MHA), and 4-mercapto-4-methyl-2 pentanone (4-MMP)) are challenging due to their high reactivity and ultra-trace concentrations, especially when using conventional gas-chromatography electron impact mass spectrometry (GC-EI-MS). We describe a method in which thiols are converted to pentafluorobenzyl (PFB) derivatives by extractive alkylation and the organic layer is evaporated prior to headspace solid phase microextraction (HS SPME) and GC-EI-MS analysis. Optimal parameters were determined by response surface area modeling. The addition of NaCl solution to the dried SPME vials prior to extraction resulted in up to less than fivefold improvement in detection limits. Using 40 mL wine samples, limits of detection for 4-MMP, 3-MH, and 3-MHA were 0.9 ng/L, 1 ng/L, and 17 ng/L, respectively. Good recovery (90%-109%) and precision (5%-11% RSD) were achieved in wine matrices. The new method was used to survey polyfunctional thiol concentrations in 61 commercial California and New York State wines produced from V. vinifera (Riesling, Gewurztraminer, Cabernet Sauvignon, Sauvignon blanc and non-varietal rose wines), V. labruscana (Niagara), and Vitis spp. (Cayuga White). Mean 4-MMP concentrations in New York Niagara (17 ng/L) were not significantly different from concentrations in Sauvignon blanc, but were significantly higher than 4-MMP in other varietal wines. PMID- 26154887 TI - Heterocycles 38. Biocatalytic Synthesis of New Heterocyclic Mannich Bases and Derivatives. AB - This paper describes the biocatalytic synthesis of new Mannich bases containing various heterocyclic rings (thiazole, furane, thiophene, pyridine) by applying the lipase catalyzed trimolecular condensation of the corresponding heterocyclic aldehydes with acetone and primary aromatic amines, in mild and eco-friendly reaction conditions. The obtained Mannich bases were acylated to their corresponding N-acetyl derivatives. All compounds were characterized by 1H-NMR, 13C-NMR and MS spectrometry. PMID- 26154889 TI - Early stage radiation-induced lung injury detected using hyperpolarized (129) Xe Morphometry: Proof-of-concept demonstration in a rat model. AB - PURPOSE: Radiation-induced lung injury (RILI) is still the major dose-limiting toxicity related to lung cancer radiation therapy, and it is difficult to predict and detect patients who are at early risk of severe pneumonitis and fibrosis. The goal of this proof-of-concept preclinical demonstration was to investigate the potential of hyperpolarized (129) Xe diffusion-weighted MRI to detect the lung morphological changes associated with early stage RILI. METHODS: Hyperpolarized (129) Xe MRI was performed using eight different diffusion sensitizations (0.0 115 s/cm(2) ) in a small group of control rats (n = 4) and rats 2 wk after radiation exposure (n = 5). The diffusion-weighted images were used to obtain morphological estimates of the pulmonary parenchyma including external radius (R), internal radius (r), alveolar sleeve depth (h), and mean airspace chord length (Lm ). The histological mean linear intercept (MLI) were obtained for five control and five irradiated animals. RESULTS: Mean R, r, and Lm were both significantly different (P < 0.02) in the irradiated rats (74 +/- 17 um, 43 +/- 12 um, and 54 +/- 17 um, respectively) compared with the control rats (100 +/- 12 um, 67 +/- 10 um, and 79 +/- 12 um, respectively). Changes in measured Lm values were consistent with changes in MLI values observed by histology. CONCLUSIONS: Hyperpolarized (129) Xe MRI provides a way to detect and measure regional microanatomical changes in lung parenchyma in a preclinical model of RILI. Magn Reson Med 75:2421-2431, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26154888 TI - Multivalent Conjugates of Sonic Hedgehog Accelerate Diabetic Wound Healing. AB - Despite their preclinical promise, few recombinant growth factors have been fully developed into effective therapies, in part, due to the short interval of therapeutic activity after administration. To address this problem, we developed nanoscale polymer conjugates for multivalent presentation of therapeutic proteins that enhance the activation of targeted cellular responses. As an example of this technology, we conjugated multiple Sonic hedgehog (Shh) proteins onto individual hyaluronic acid biopolymers to generate multivalent protein clusters at defined ratios (i.e., valencies) that yield enhanced Shh pathway activation at equivalent concentrations relative to unconjugated Shh. In this study, we investigated whether these multivalent conjugates (mvShh) could be used to improve the therapeutic function of Shh. We found that a single treatment with mvShh significantly accelerated the closure of full-thickness wounds in diabetic (db/db) mice compared to either an equivalent dose of unconjugated Shh or the vehicle control. Furthermore, we identified specific indicators of wound healing in fibroblasts and endothelial cells (i.e., transcriptional activation and cell migration) that were activated by mvShh in vitro and at concentrations approximately an order of magnitude lower than the unconjugated Shh. Taken together, our findings suggest that mvShh conjugates exhibit greater potency to activate the Shh pathway, and this multivalency advantage improves its therapeutic effect to accelerate wound closure in a diabetic animal model. Our strategy of multivalent protein presentation using nanoscale polymer conjugates has the potential to make a significant impact on the development of protein based therapies by improving their in vivo performance. PMID- 26154891 TI - Ascorbic Acid Promoted Oxidative Arylation of Vinyl Arenes to 2-Aryl Acetophenones without Irradiation at Room Temperature under Aerobic Conditions. AB - A convenient and general protocol for oxidative arylation of vinyl arenes by aryl radicals generated in situ from arene diazonium fluoroborates promoted by ascorbic acid in air at room temperature has been developed in the absence of any additive and visible light irradiation. A series of diversely substituted 2-aryl acetophenones have been obtained in good yields by this procedure. PMID- 26154890 TI - A Molecular Approach Designed to Limit the Replication of Mature DENV2 in Host Cells. AB - Dengue virus (DENV) is an arthropod-borne virus, which belongs to the Flaviviridae family, and completes its life cycle in two hosts: humans and mosquitoes. For DENV maturation, the surface pre-membrane (prM) protein is cleaved to form a mature membrane protein (M) by furin, which is a cellular enzyme subsequently releasing the mature virus from the host dendritic cell. The objective of the current study was to inhibit mature DENV isotype 2 (DENV2) by RNA-interference in a Vero-81 cell line. Mature DENV2 was propagated in and isolated from U937 cells expressing dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin. Maturation of DENV2 was confirmed by Western blot analysis, where virus stock lacking prM was considered mature. Inhibition studies were carried out by transfection of Vero-81 cells with six synthetic siRNAs along with a control siRNA. Reduction in cellular DENV2 was observed also by focus-reduction assay, immunofluorescence assay (IFA), and real time quantitative polymerase chain reaction (RT-qPCR). Cells transfected with DENV2SsiRNA2, which was targeting the structural region M of mature DENV2, was able to reduce DENV2 titer by up to 85% in focus reduction assays. A significant reduction in mature DENV2 RNA load was observed by RT-qPCR, confirming the previous findings. IFA also revealed reduced levels of cellular DENV2. These results demonstrated that mature DENV2 can be effectively inhibited by synthetic siRNA targeting the structural region of the genome. Mature DENV2 can be successfully inhibited by siRNAs, and specifically high knock-down efficiency is observed by siRNAs against M region of mature DENV2. This study shows that M represents a potential target for RNAi based inhibitory approaches. PMID- 26154893 TI - Syntheses and Reactivity Studies of Square-Planar Diamido-Pyridine Complexes Based on Earth-Abundant First-Row Transition Elements. AB - The new square-planar complexes M[NNN](pyridine) (M = Fe (1), Co(2); NNN = 2,6 bis(2,6-diisopropylphenylamidomethyl)pyridine) were synthesized and fully characterized to investigate small molecule activation on this platform and also associated ligand innocence. The equatorial pyridine solvent moiety could not be removed; a new bis-ligand species Co[NNN.H]2 (3) was synthesized in low yield while attempting to make the base-free derivative. Attempts to prepare the Ni analogue of 1 and 2 instead yielded crystals of a di-imino-pyridine complex Ni[PDI]Cl (4) (PDI = 2,6-bis(2,6-diisopropylphenyliminomethyl)pyridine), following loss of methylene backbone hydrogen atoms. Structural analysis indicates that the PDI ligand is a mono-anionic radical. This susceptibility of the ligand to oxidative dehydrogenation was also shown when the reaction of 2 with 2 equiv of trityl chloride yielded a new complex with an asymmetric imino amino pyridine ligand Co[NNN']Cl2 (5) (NNN' = 2-(2,6 (diisopropylphenyliminomethyl)-6-(diisopropylphenylamidomethyl)-pyridine) in good yield. PMID- 26154894 TI - Flexibility and Charge of Solutes as Factors That Determine Their Diffusion in Casein Suspensions and Gels. AB - This work explores the influence of both the physicochemical characteristics of solutes and the solute-matrix interactions on diffusion in casein systems. Diffusion coefficients of three solute groups (dextrans, proteins, and peptides) presenting different physicochemical characteristics, such as molecular flexibility and charge, were measured using the technique of fluorescence recovery after photobleaching (FRAP). The casein systems had the same casein concentration, but different microstructures (suspension or gel), and/or a different pH (5.2 or 6.6). Flexible solutes diffused more rapidly through the casein systems than the rigid ones. Electrostatic interactions between charged solute molecules and the casein matrix were partly screened due to the high ionic strength of the systems. As a consequence, it was the flexibility of the solute molecule (rather than its charge) that most influenced its diffusion through casein systems. PMID- 26154895 TI - Dire need of changes in the methods for assessing university faculty productivity in developing countries. AB - Publishing has become a necessity for promotion of faculty in academia. The faculties in developing countries face considerable difficulties publishing due to their prime focus on clinical approaches and resources for proper research. This often leaves no room for the pressured clinicians but to pursue poor quality publications just for the sake of promotion when the time for their promotion comes. The authors suggest establishing separate promotion tracks besides research in these underprivileged areas in order to avoid infestation of original research with poor ones. PMID- 26154892 TI - Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation. AB - The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of >90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal alpha2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease. PMID- 26154896 TI - Solar Synthesis of PbS-SnS2 Superstructure Nanoparticles. AB - We report the synthesis and supporting density-functional-theory computations for a closed-cage, misfit layered-compound superstructure from PbS-SnS2, generated by highly concentrated sunlight from a precursor mixture of Pb, SnS2, and graphite. The unique reactor conditions created in our solar furnace are found to be particularly conducive to the formation of these nanomaterials. Detailed structural and chemical characterization revealed a spontaneous inside-out formation mechanism, with a broad range of nonhollow fullerene-like structures starting at a diameter of ~20 nm and a wall thickness of ~5 layers. The computations also reveal a counterintuitive charge transfer pathway from the SnS2 layers to the PbS layers, which indicates that, in contrast to binary-layered compounds where it is principally van der Waals forces that hold the layers together, polar forces appear to be as important in stabilizing superstructures of misfit layered compounds. PMID- 26154897 TI - To address emerging infections, we must invest in enduring systems: The kinetics and dynamics of health systems strengthening. AB - Clinical pharmacology uses foundational principles of pharmacokinetics (PK) and pharmacodynamics (PD) to address medication use spanning a continuum from molecules to the masses. In the realm of infectious diseases, PK/PD attributes are considered especially important, because subtherapeutic dosing of antibiotics has been associated with poorer clinical outcomes in patients and increased incidences of drug resistance in populations. In consideration of these PK/PD principles, we will describe the analogous relationship between health systems strengthening, including for educating healthcare providers about emerging infections, and the tenets of therapeutic drug monitoring. PMID- 26154898 TI - Structure design and manufacturing of layered bioceramic scaffolds for load bearing bone reconstruction. AB - Bioceramic scaffolds with desired bone regeneration functions have the potential to become real alternatives to autologous bone grafts for reconstruction of load bearing and critical-sized segmental bone defects. The aim of this paper was to develop a layered scaffold structure that has the biodegradable function of common monolithic scaffolds and adequate mechanical function for surgical fixing and after surgery support. The exemplary case of this study is assumed to be a large-segment tibia or femur bone repair. The layered scaffold structure consists of a macro porous hydroxyapatite-wollastonite layer and a strong dense zirconia matrix dense layer. The bio-functional scaffold layer with interconnected freeze dried porous structures shows excellent apatite formation, cell attachment, and cell proliferation capabilities. The mechanical functional layer provides a bending strength matching that of the compact bone. PMID- 26154899 TI - Endoscopic endonasal transclival approach to a pontine cavernous malformation: case report. AB - Cavernous malformations of the brainstem are difficult to manage because of their location in eloquent tissue and their high propensity for symptomatic bleeding. Traditional neurosurgical approaches are often associated with significant morbidities. Here we present the case of a 15 year-old male patient with an acute onset of severe cephalalgia associated with neurological signs (right cranial nerve VI, VII and VIII palsies). MRI revealed a ventral pontine cavernous malformation with signs of recent bleeding. The lesion was removed by way of an endoscopic endonasal transclival approach. Post-operative neurological examination showed a dramatic improvement in cranial nerves function. The patient remains stable two years after surgery. PMID- 26154900 TI - Catheter-Associated Thrombosis: A Journey of a Thousand Miles Starts With the First Step. PMID- 26154901 TI - The Elephant of Red Cell Transfusion: Is It All Tusks? PMID- 26154902 TI - Tight Glucose Control With Insulin Following Pediatric Cardiac Surgery: Still "Muscling" on in Search of Answers! PMID- 26154903 TI - Innovation, Cost, and Sustainability of Pediatric Ventricular Assist Device Programs. PMID- 26154904 TI - CT After Pediatric Out-of-Hospital Cardiac Arrest-Where To Go Next? PMID- 26154905 TI - It Is Time to Care About Ventilator-Associated Tracheobronchitis. PMID- 26154906 TI - Unplanned Extubations: Where Is the Harm? PMID- 26154907 TI - A Multidisciplinary Mobile Nutritional Assessment Model for Family-Supported Dietary Optimization in Home-Ventilated Children. PMID- 26154908 TI - How We Manage Hyperferritinemic Sepsis-Related Multiple Organ Dysfunction Syndrome/Macrophage Activation Syndrome/Secondary Hemophagocytic Lymphohistiocytosis Histiocytosis. PMID- 26154909 TI - Can Teaching Programs Optimize Nutritional Evaluation and Improve Outcome in the PICU? PMID- 26154910 TI - The authors reply. PMID- 26154911 TI - What Will Be the Consensus of Pediatric Intensivists Regarding the Diagnosis of Pediatric Acute Respiratory Distress Syndrome? PMID- 26154912 TI - The authors reply. PMID- 26154913 TI - The divergent roles of macrophages in solid organ transplantation. AB - PURPOSE OF REVIEW: This review summarizes the phenotype and function of macrophages in the context of solid organ transplantation and will focus on fundamental insights into their paradoxical pro-inflammatory versus suppressive function. We will also discuss the therapeutic potential of regulatory macrophages in tolerance induction. RECENT FINDINGS: Macrophages are emerging as an essential element of solid organ transplantation. Macrophages are involved in the pathogenesis of ischemia reperfusion injury, as well as both acute and chronic rejection, exacerbating injury through secretion of inflammatory effectors and by amplifying adaptive immune responses. Notably, not all responses associated with macrophages are deleterious to the graft, and graft protection can in fact be conferred by macrophages. This has been attributed to the presence of macrophages with tissue-repair capabilities, as well as the effects of regulatory macrophages. SUMMARY: The explosion of new information on the role of macrophages in solid organ transplantation has opened up new avenues of research and the possibility of therapeutic intervention. However, the role of myeloid cells in graft rejection, resolution of rejection and tissue repair remains poorly understood. A better understanding of plasticity and regulation of monocyte polarization is vital for the development of new therapies for the treatment of acute and chronic transplant rejection. PMID- 26154914 TI - Immunosenescence in renal transplantation: a changing balance of innate and adaptive immunity. AB - PURPOSE OF REVIEW: With global demographic changes and an overall improved healthcare, more older end-stage renal disease (ESRD) patients receive kidney transplants. At the same time, organs from older donors are utilized more frequently. Those developments have and will continue to impact allocation, immunosuppression and efforts improving organ quality. RECENT FINDINGS: Findings mainly outside the field of transplantation have provided insights into mechanisms that drive immunosenescence and immunogenicity, thus providing a rationale for an age-adapted immunosuppression and relevant clinical trials in the elderly. With fewer rejections in the elderly, alloimmune responses appear to be characterized by a decline in effectiveness and an augmented unspecific immune response. SUMMARY: Immunosenescence displays broad and ambivalent effects in elderly transplant recipients. Those changes appear to compensate a decline in allospecific effectiveness by a shift towards an augmented unspecific immune response. Immunosuppression needs to target those age-specific changes to optimize outcomes in elderly transplant recipients. PMID- 26154915 TI - Incidence and mortality trends of aspiration pneumonia in Parkinson's disease in the United States, 1979-2010. AB - INTRODUCTION: Careful examination of long-term analyses and trends is essential in understanding the medico-economic burden of this common complication. We sought to describe the long-term (32-year) trends of incidence and mortality in PD patients hospitalized with aspiration pneumonia (AsPNA). METHODS: Incidence and mortality of AsPNA in hospitalized PD versus non-PD patients was assessed by logistic regression analysis applied to a national database between the years 1979 and 2010. Covariates such as age-decennium, gender, year AsPNA occurred, and the interactions with PD diagnosis were investigated. Rate of AsPNA and mortality over the 32-years was trended and compared. RESULTS: AsPNA occurred in 3.6% of PD patients and 1.0% of non-PD patients. The average mortality for PD patients was less (17% vs. 22%). Long-term (32-year) trends revealed a nearly 10-fold increase in incidence of AsPNA in PD (0.4% in 1979, 4.9% in 2010), decreasing mortality overtime, higher likelihood in males, and increasing average age of AsPNA patients (steeper increase in PD). All p-values<0.05. In regression analysis, each successive year had a slight increase in odds of AsPNA (OR 1.03 in PD, OR1.06 in non-PD). CONCLUSIONS: Trends over 32 years revealed a 10-fold increase in AsPNA among PD and non-PD patients, and an associated decrease in mortality. Our data suggest that PD patients are living longer, have slightly more AsPNA, but a lower mortality than was seen in past decades. Further research should investigate the causes of AsPNA in PD, and also potential interventions to decrease its occurrence. PMID- 26154916 TI - Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment. AB - Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 degrees C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy. PMID- 26154917 TI - Flowerlike CeO2 microspheres coated with Sr2Fe1.5Mo0.5Ox nanoparticles for an advanced fuel cell. AB - Flowerlike CeO2 coated with Sr2Fe1.5Mo0.5Ox (Sr-Fe-Mo-oxide) nanoparticles exhibits enhanced conductivity at low temperatures (300-600 degrees C), e.g. 0.12 S cm(-1) at 600 degrees C, this is comparable to pure ceria (0.1 S cm(-1) at 800 degrees C). Advanced single layer fuel cell was constructed using the flowerlike CeO2/Sr-Fe-Mo-oxide layer attached to a Ni-foam layer coated with the conducting transition metal oxide. Such fuel cell has yielded a peak power density of 802 mWcm(-2) at 550 degrees C. The mechanism of enhanced conductivity and cell performance were analyzed. These results provide a promising strategy for developing advanced low-temperature SOFCs. PMID- 26154918 TI - Acetazolamide for the treatment of idiopathic intracranial hypertension. AB - Idiopathic intracranial hypertension (IIH) is characterized by an increase of intracranial pressure in the absence of neurologic tumors. The sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor (CAI) acetazolamide (AAZ), a compound developed in the 1950s as a diuretic drug and presently used as an antiglaucoma, antiepileptic and diuretic agent, is effective in the treatment of IIH. AAZ is a low nanomolar inhibitor of CA isoforms involved in cerebrospinal fluid (CSF) secretion. Inhibition of brain/choroid plexus CA II, IV, VA and XII leads to a decreased CSF fluid secretion and control of the intracranial pressure. Although many sulfonamide/sulfamate CAIs are in clinical use for decades, apparently only AAZ is being currently used clinically for IIH. We speculate that more lipophilic CAIs such as methazolamide, zonisamide or topiramate should lead to a more effective control of increased intracranial pressure, thus having the opportunity to become useful in the management of IIH. PMID- 26154919 TI - Short and highly efficient synthesis of lipid peroxidation inhibitor pyrrolostatin and some analogues thereof. AB - A highly efficient and scalable synthesis of potent lipid peroxidation inhibitor pyrrolostatin is reported (4 steps, 48%). In addition to the synthesis of the natural product, strategies for the preparation of analogues differing in the three structural subunits, the polar head group, the N-substituent and the lipophilic tail are described. PMID- 26154920 TI - Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells. AB - PURPOSE: Increased expression of transforming growth factor-beta2 (TGF-beta2) is reported in the conjunctiva of dry eye patients with no increase of anti inflammatory activity of TGF-beta2. Our aim was to compare the expression of molecules involved in TGF-beta2 activation, thrombospondin-1 (TSP-1) and CD36, during murine and human conjunctival inflammation. METHODS: Human conjunctival tissue from cadaveric donors, human conjunctival epithelial primary cells and fibroblasts, and murine conjunctivas were immunostained for TSP-1, CD36, or TGF beta2. Inflamed conjunctival tissues were obtained from C57BL/6 wild-type (WT) mice induced to develop experimental dry eye (EDE) with 10 days of desiccating conditions and scopolamine injections and TSP-1-deficient (TSP1(-/-)) mice, which spontaneously develop Sjogren's syndrome-associated conjunctival inflammation with age. Immunostaining intensities were compared using ImageJ software. Cultures of human conjunctival fibroblasts were stimulated with IL-1beta and both secreted protein and message levels of TSP-1, CD36, and TGF-beta2 were analyzed. RESULTS: TSP-1 and CD36 were detectable in human and murine conjunctival tissues as well as primary conjunctival epithelial cells and fibroblasts. Increased conjunctival immunostaining of TGF-beta2 and reduced CD36 were detected in EDE mice compared with WT mice. Interestingly, increased TGF-beta2 and CD36 conjunctival immunostaining was detected in TSP1(-/-) mice. The expression of TSP 1 and CD36 was downregulated in IL-1beta-stimulated conjunctival fibroblasts at both the protein and message level, while active TGF-beta2 was undetected. CONCLUSIONS: The absence or reduced expression of either of the molecules involved in TGF-beta2 activation supports proinflammatory conditions in the conjunctiva. Changes in TSP-1 and CD36 may serve as potential biomarkers of conjunctival inflammation. PMID- 26154921 TI - Model for prediction of pediatric OSA: Proposal for a clinical decision rule. AB - OBJECTIVES/HYPOTHESIS: Obstructive sleep apnea (OSA) is a syndrome frequently diagnosed in children; however, it lacks optimal diagnostic methods. This study aimed to provide a clinical decision rule for predicting pediatric OSA using commonly available clinical information. STUDY DESIGN: A prospective cohort study. METHODS: Children between the ages of 3 to 6 years-old, referred for an otorhinolaryngology consultation due to clinical suspicion of OSA, were recruited from January to June 2014. At baseline age, weight, height, gender, body mass index, Pediatric Sleep Questionnaire (PSQ) scores, tonsil size, and oxygen desaturation index (ODI) were assessed. A logistic regression modeling was used with backward stepwise elimination to develop a prediction model. RESULTS: Sixty seven children were included with a mean age of 4.51 years. Of the 67 children included in this study, 25 (37.3%) subjects were diagnosed with pediatric OSA. Significant predictors of pediatric OSA in the final model (odds ratio, 95% confidence interval) included PSQ score (5.12; 3.3-6.5), ODI (1.34; 1.0-1.79) and tonsil size (6.7; 3.22-9.75). The final decision rule had a sensitivity of 88% and a specificity of 86%. The area under the receiver operating characteristic curve was 0.897. CONCLUSION: The proposed clinical decision rule, based on three readily available variables, is a promising discriminating instrument for prediction of OSA among children between 3 and 6 years. LEVEL OF EVIDENCE: 2b. PMID- 26154922 TI - Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits. AB - The diagnosis of membranoproliferative glomerulonephritis (MPGN) has recently undergone change from an electron microscopy-based classification scheme to one based largely on immunofluorescence findings. This change is due to the recognition that many of these cases are driven by abnormalities of the alternative complement cascade, resulting in the concept of C3 glomerulopathy. Here we reviewed our case files to identify those with an MPGN pattern that show false negative staining for monoclonal immunoglobulins by routine immunofluorescence. Monoclonal immunoglobulin deposits were unmasked by performing immunofluorescence on formalin-fixed paraffin embedded tissue after protease digestion. Clinico-pathological details of 16 such cases with a mean serum creatinine of 2.7 mg/dl and mean 24 h proteinuria of 7.1 g were then determined. Hypocomplementemia was present in two-thirds of patients. Fourteen patients had a paraprotein on serum immunofixation, all of which matched the biopsy immunofluorescence staining pattern. Bone marrow biopsy showed plasma cell dyscrasia or B-cell lymphoproliferative disorder in 13 patients. Ten of these patients had findings on biopsy most consistent with C3 glomerulonephritis prior to performing paraffin immunofluorescence. Thus a high index of suspicion is necessary to avoid misdiagnosis in these cases, as many would have been mistakenly diagnosed as C3 glomerulopathy or unclassified MPGN if paraffin immunofluorescence was not performed. PMID- 26154923 TI - Use of an ECG-based confirmatory technique for bedside placement of reverse tunneled cuffed dialysis catheters in three morbidly obese patients. AB - We are currently in the midst of a worldwide obesity epidemic, including in patients with end-stage kidney disease. Placing hemodialysis catheters is a particular challenge in patients with extreme obesity. Here we describe the merging of two technologies to place catheters in patients who are too heavy (over 225 kg) to be placed safely on a procedure table for fluoroscopic guidance. The first technology is ECG-guided placement of catheters, well established for guidance of peripherally inserted central catheters (PICCs) and tunneled and nontunneled central venous catheters. The second is reverse-tunneling dialysis catheters, which allow precise placement of the tip of the catheter before creating the tunnel. We successfully placed catheters in three morbidly obese patients with acute kidney injury and followed them until their kidneys recovered and the catheters were removed. The catheters were placed in the patient's bed in a procedure room with subsequent confirmatory chest radiographs. Catheter performance based on blood flow rates was excellent and there were no complications. We suggest placement of ECG-guided tunneled hemodialysis catheters using a reversed-tunneling technique in those patients with extreme obesity who are too heavy to place on a fluoroscopy procedure table. PMID- 26154924 TI - Towards an understanding of kidney diseases associated with WT1 mutations. AB - Mutations in Wilms' tumor 1 (WT1) cause a wide spectrum of renal manifestations, eventually leading to end-stage kidney failure. Insufficient understanding of WT1's molecular functions in kidney development has hampered efficient therapeutic applications for WT1-associated diseases. Recently, the generation and characterization of mouse models and application of multiple state-of-the-art approaches have significantly expanded our understanding of the molecular mechanisms of how WT1 mutations lead to kidney failure. Here, we discuss the WT1 binding consensus and illustrate the major roles of WT1 in different cell populations in kidney biology. WT1 controls metanephric mesenchyme (MM) self renewal and proliferation mainly by regulating FGF and BMP-pSMAD signaling pathways as well as Sall1 and Pax2, encoding key transcription factors; WT1 drives MM differentiation and mesenchyme-epithelial transition by targeting Fgf8 and Wnt4; WT1 defines podocyte identity by activation of other podocyte-specific transcription factors, including Mafb, Lmx1b, FoxC2, and Tcf21. These factors potentially cooperate with WT1 regulating the expression of components and regulators of the cytoskeleton for establishing podocyte polarity, slit diaphragm structure, and focal adhesion to the glomerular basement membrane. Understanding of WT1's function in kidney biology including WT1-regulated pathways will give insights that will eventually help therapeutic applications. PMID- 26154925 TI - Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults. AB - Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 MUg/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77 (95% CI 0.62 0.96)) and a 10% lower risk of mortality (hazard ratio 0.90 (95% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function. PMID- 26154926 TI - Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis stimulating agent use and maintains hemoglobin in hemodialysis patients. AB - Ferric pyrophosphate citrate (FPC) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin. The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent (ESA) use and maintain hemoglobin in hemodialysis patients. This 9-month, randomized, placebo-controlled, double-blind, multicenter clinical study included 103 patients undergoing hemodialysis 3-4 times weekly. The FPC group received dialysate containing 2 MUmol/l of iron. The placebo group received standard dialysate. A blinded central anemia management group facilitated ESA dose adjustments. Intravenous iron was administered according to the approved indication when ferritin levels fell below 200 MUg/l. The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment. Secondary end points included intravenous iron use and safety. At the end of treatment, there was a significant 35% reduction in prescribed ESA dose in FPC treated patients compared with placebo. The FPC patients used 51% less intravenous iron than placebo. Adverse and serious adverse events were similar in both groups. Thus, FPC delivered via dialysate significantly reduces the prescribed ESA dose and the amount of intravenous iron needed to maintain hemoglobin in chronic hemodialysis patients. PMID- 26154927 TI - The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier. AB - Podocyte dysfunction impairs the size selectivity of the glomerular filter, leading to proteinuria, hypoalbuminuria, and edema, clinically defined as nephrotic syndrome. Hereditary forms of nephrotic syndrome are linked to mutations in podocyte-specific genes. To identify genes contributing to podocyte dysfunction in acquired nephrotic syndrome, we studied human glomerular gene expression data sets for glomerular-enriched gene transcripts differentially regulated between pretransplant biopsy samples and biopsies from patients with nephrotic syndrome. Candidate genes were screened by in situ hybridization for expression in the zebrafish pronephros, an easy-to-use in vivo assay system to assess podocyte function. One glomerulus-enriched product was the Rho-GTPase binding protein, IQGAP2. Immunohistochemistry found a strong presence of IQGAP2 in normal human and zebrafish podocytes. In zebrafish larvae, morpholino-based knockdown of iqgap2 caused a mild foot process effacement of zebrafish podocytes and a cystic dilation of the urinary space of Bowman's capsule upon onset of urinary filtration. Moreover, the glomerulus of zebrafish morphants showed a glomerular permeability for injected high-molecular-weight dextrans, indicating an impaired size selectivity of the glomerular filter. Thus, IQGAP2 is a Rho GTPase binding protein, highly abundant in human and zebrafish podocytes, which controls normal podocyte structure and function as evidenced in the zebrafish pronephros. PMID- 26154928 TI - Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury. AB - In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial. PMID- 26154930 TI - Intracoronary Transfusion of Circulation-Derived CD34+ Cells Improves Left Ventricular Function in Patients With End-Stage Diffuse Coronary Artery Disease Unsuitable for Coronary Intervention. AB - OBJECTIVE: This study tested the hypothesis that intra-coronary transfusion of circulation-derived autologous CD34+ cells can improve ischemia-related left ventricular dysfunction in patients with severe diffuse coronary artery disease refractory to medication and unsuitable for coronary intervention. DESIGN: A prospective, randomized, double-blinded phase I clinical trial. SETTING: Tertiary care center. PATIENTS: Thirty-eight patients with severe diffuse coronary artery disease were randomized into group 1 and group 2 receiving CD34+ cell infusion with dosages of 1.0 x 107 and 3.0 x 107 cells/vessel, respectively, after subcutaneous G-CSF injection (5 MUg/kg twice a day for 4 d). INTERVENTIONS: Cardiac catheterization and intra-coronary administration of CD34+ cells. MEASUREMENTS AND MAIN RESULTS: This clinical trial was to test effectiveness and safety of these two different dosages of CD34+ cells in the setting of severe diffuse coronary artery disease. Blood samples were collected for endothelial progenitor cell culture before and after granulocyte colony-stimulating factor injection for matrigel-assay and comparison of levels of soluble angiogenesis factors (vascular endothelial growth factor, epithelial growth factor, hepatocyte growth factor, angiopoietin-1, and transforming growth factor-beta). Procedural safety was 100% with all patients uneventfully discharged. The numbers of endothelial progenitor cells in blood samples from coronary sinus after transfusion were higher than those in circulation, and the circulatory level was higher after granulocyte colony-stimulating factor treatment (all p < 0.001). Cardiac MRI and three-dimensional echocardiography at 6 month and angiographic follow-up at 9 month showed improvement in left ventricular ejection fraction (p < 0.001) and consistent increase in neovascularization (p < 0.001), respectively, in both groups. Despite good correlation in angiogenesis between 9-month angiography and matrigel-assay (p < 0.001), no significant correlation was noted in of soluble angiogenesis factor levels. Angina and heart failure were improved in both groups at 12-month follow-up (all p < 0.001). The survival rate at 18.5 month follow-up was 94.7% (n = 36). CONCLUSIONS: CD34+ cell therapy was safe and efficacious in improving heart function for patients with severe diffuse coronary artery disease unsuitable for coronary intervention and with poor response to pharmacotherapy. PMID- 26154929 TI - Integrating Palliative Care Into the Care of Neurocritically Ill Patients: A Report From the Improving Palliative Care in the ICU Project Advisory Board and the Center to Advance Palliative Care. AB - OBJECTIVES: To describe unique features of neurocritical illness that are relevant to provision of high-quality palliative care; to discuss key prognostic aids and their limitations for neurocritical illnesses; to review challenges and strategies for establishing realistic goals of care for patients in the neuro ICU; and to describe elements of best practice concerning symptom management, limitation of life support, and organ donation for the neurocritically ill. DATA SOURCES: A search of PubMed and MEDLINE was conducted from inception through January 2015 for all English-language articles using the term "palliative care," "supportive care," "end-of-life care," "withdrawal of life-sustaining therapy," "limitation of life support," "prognosis," or "goals of care" together with "neurocritical care," "neurointensive care," "neurological," "stroke," "subarachnoid hemorrhage," "intracerebral hemorrhage," or "brain injury." DATA EXTRACTION AND SYNTHESIS: We reviewed the existing literature on delivery of palliative care in the neurointensive care unit setting, focusing on challenges and strategies for establishing realistic and appropriate goals of care, symptom management, organ donation, and other considerations related to use and limitation of life-sustaining therapies for neurocritically ill patients. Based on review of these articles and the experiences of our interdisciplinary/interprofessional expert advisory board, this report was prepared to guide critical care staff, palliative care specialists, and others who practice in this setting. CONCLUSIONS: Most neurocritically ill patients and their families face the sudden onset of devastating cognitive and functional changes that challenge clinicians to provide patient-centered palliative care within a complex and often uncertain prognostic environment. Application of palliative care principles concerning symptom relief, goal setting, and family emotional support will provide clinicians a framework to address decision making at a time of crisis that enhances patient/family autonomy and clinician professionalism. PMID- 26154931 TI - Clinical and Physiological Events That Contribute to the Success Rate of Finding "Optimal" Cerebral Perfusion Pressure in Severe Brain Trauma Patients. AB - OBJECTIVE: Recently, a concept of an individually targeted level of cerebral perfusion pressure that aims to restore impaired cerebral vasoreactivity has been advocated after traumatic brain injury. The relationship between cerebral perfusion pressure and pressure reactivity index normally is supposed to have a U shape with its minimum interpreted as the value of "optimal" cerebral perfusion pressure. The aim of this study is to investigate the relation between the absence of the optimal cerebral perfusion pressure curve and physiological variables, clinical factors, and interventions. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurocritical care units in two university centers. PATIENTS: Between May 2012 and December 2013, a total of 48 traumatic brain injury patients were studied with real-time annotation of predefined clinical events. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients had continuous monitoring of arterial blood pressure, intracranial pressure, and cerebral perfusion pressure, with real-time calculations of pressure reactivity index and optimal cerebral perfusion pressure using ICM+ software (Cambridge Enterprise, University of Cambridge, Cambridge, UK). Selected clinical events were inserted on a daily basis, including changes in physiological variables, sedativeanalgesic drugs, vasoactive drugs, and medical/surgical therapies for intracranial hypertension. The collected data were divided into 4-hour periods, with the primary outcome being absence of the optimal cerebral perfusion pressure curve. For every period, mean values (+/- SDs) of arterial blood pressure, intracranial pressure, pressure reactivity index, and other physiological variables were calculated; clinical events were organized using predefined scales. In 28% of all 1,561 periods, an optimal cerebral perfusion pressure curve was absent. A generalized linear mixed model with binary logistic regression was fitted. Absence of slow arterial blood pressure waves (odds ratio, 2.7; p < 0.001), higher pressure reactivity index values (odds ratio, 2.9; p < 0.001), lower amount of sedative-analgesic drugs (odds ratio, 1.9; p = 0.03), higher vasoactive medication dose (odds ratio, 3.2; p = 0.02), no administration of maintenance neuromuscular blockers (odds ratio, 1.7; p < 0.01), and following decompressive craniectomy (odds ratio, 1.8; p < 0.01) were independently associated with optimal cerebral perfusion pressure curve absence. CONCLUSIONS: This study identified six factors that were independently associated with absence of optimal cerebral perfusion pressure curves. PMID- 26154932 TI - Atrial Fibrillation Is an Independent Predictor of Mortality in Critically Ill Patients. AB - OBJECTIVES: Atrial fibrillation has been associated with increased mortality in critically ill patients. We sought to determine whether atrial fibrillation in the ICU is an independent risk factor for death. A secondary objective was to determine if patients with new-onset atrial fibrillation have different risk factors or outcomes compared with patients with a previous history of atrial fibrillation. DESIGN: Prospective observational cohort study. SETTING: Medical and general surgical ICUs in a tertiary academic medical center. PATIENTS: One thousand seven hundred seventy critically ill patients requiring at least 2 days in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, medical history, development of atrial fibrillation, fluid balance, echocardiographic findings, medication administration, and hospital mortality were collected during the first 4 days of ICU admission. Atrial fibrillation occurred in 236 patients (13%) (Any AF). Of these, 123 patients (7%) had no prior atrial fibrillation (New-onset AF) while the remaining 113 (6%) had recurrent atrial fibrillation (Recurrent AF). Any AF was associated with male gender, Caucasian race, increased age, cardiac disease, organ failures, and disease severity. Patients with Any AF had increased mortality compared with those without atrial fibrillation (31% vs 17%; p < 0.001), and Any AF was independently associated with death (odds ratio, 1.62; 95% CI, 1.14-2.29; p = 0.007) in multivariable analysis controlling for severity of illness and other confounders. The association of atrial fibrillation with death was magnified in patients without sepsis (odds ratio, 2.92; 95% CI, 1.52-5.60; p = 0.001). Treatment for atrial fibrillation had no effect on hospital mortality. New-onset AF and Recurrent AF were each associated with increased mortality. New-onset AF, but not Recurrent AF, was associated with increased diastolic dysfunction and vasopressor use and a greater cumulative positive fluid balance. CONCLUSIONS: Atrial fibrillation in critical illness, whether new-onset or recurrent, is independently associated with increased hospital mortality, especially in patients without sepsis. PMID- 26154933 TI - Single Deranged Physiologic Parameters Are Associated With Mortality in a Low Income Country. AB - OBJECTIVE: To investigate whether deranged physiologic parameters at admission to an ICU in Tanzania are associated with in-hospital mortality and compare single deranged physiologic parameters to a more complex scoring system. DESIGN: Prospective, observational cohort study of patient notes and admission records. Data were collected on vital signs at admission to the ICU, patient characteristics, and outcomes. Cutoffs for deranged physiologic parameters were defined a priori and their association with in-hospital mortality was analyzed using multivariable logistic regression. SETTING: ICU at Muhimbili National Hospital, Dar es Salaam, Tanzania. PATIENTS: All adults admitted to the ICU in a 15-month period. MEASUREMENTS AND MAIN RESULTS: Two hundred sixty-nine patients were included: 54% female, median age 35 years. In-hospital mortality was 50%. At admission, 69% of patients had one or more deranged physiologic parameter. Sixty four percent of the patients with a deranged physiologic parameter died in hospital compared with 18% without (p < 0.001). The presence of a deranged physiologic parameter was associated with mortality (adjusted odds ratio, 4.64; 95% CI, 1.95-11.09). Mortality increased with increasing number of deranged physiologic parameters (odds ratio per deranged physiologic parameter, 2.24 [1.53 3.26]). Every individual deranged physiologic parameter was associated with mortality with unadjusted odds ratios between 1.92 and 16.16. A National Early Warning Score of greater than or equal to 7 had an association with mortality (odds ratio, 2.51 [1.23-5.14]). CONCLUSION: Single deranged physiologic parameters at admission are associated with mortality in a critically ill population in a low-income country. As a measure of illness severity, single deranged physiologic parameters are as useful as a compound scoring system in this setting and could be termed "danger signs." Danger signs may be suitable for the basis of routines to identify and treat critically ill patients. PMID- 26154935 TI - Early Detection of Preterm Intraventricular Hemorrhage From Clinical Electroencephalography. AB - OBJECTIVES: Intraventricular hemorrhage is a common neurologic complication of extremely preterm birth and leads to lifelong neurodevelopmental disabilities. Early bedside detection of intraventricular hemorrhage is crucial to enabling timely interventions. We sought to detect early markers of brain activity that preempt the occurrence of intraventricular hemorrhage in extremely preterm infants during the first postnatal days. DESIGN: Cross-sectional study. SETTING: Level III neonatal ICU. PATIENTS: Twenty-five extremely preterm infants (22-28 wk gestational age). MEASUREMENTS AND MAIN RESULTS: We quantitatively assessed electroencephalography in the first 72 hours of postnatal life, focusing on the electrical burst activity of the preterm. Cranial ultrasound was performed on day 1 (0-24 hr) and day 3 (48-72 hr). Outcomes were categorized into three classes: 1) no intraventricular hemorrhage (grade 0); 2) mild-moderate intraventricular hemorrhage (grades 1-2, i.e., germinal matrix hemorrhages or intraventricular hemorrhage without ventricular dilatation, respectively); and 3) severe intraventricular hemorrhage (grades 3-4, i.e., intraventricular hemorrhage with ventricular dilatation or intraparenchymal involvement). Quantitative assessment of electroencephalography burst shapes was used to preempt the occurrence and severity of intraventricular hemorrhage as detected by ultrasound. The shapes of electroencephalography bursts found in the intraventricular hemorrhage infants were significantly sharper (F = 13.78; p < 0.0001) and less symmetric (F = 6.91; p < 0.015) than in preterm infants without intraventricular hemorrhage. Diagnostic discrimination of intraventricular hemorrhage infants using measures of burst symmetry and sharpness yielded high true-positive rates (82% and 88%, respectively) and low false-positive rates (19% and 8%). Conventional electroencephalography measures of interburst intervals and burst counts were not significantly associated with intraventricular hemorrhage. CONCLUSIONS: Detection of intraventricular hemorrhage during the first postnatal days is possible from bedside measures of brain activity prior to ultrasound confirmation of intraventricular hemorrhage. Significantly, our novel automated assessment of electroencephalography preempts the occurrence of intraventricular hemorrhage in the extremely preterm. Early bedside detection of intraventricular hemorrhage holds promise for advancing individual care, targeted therapeutic trials, and understanding mechanisms of brain injury in neonates. PMID- 26154934 TI - Association of Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients. AB - OBJECTIVES: Hyperchloremia is frequently observed in critically ill patients in the ICU. Our study aimed to examine the association of serum chloride (Cl) levels with hospital mortality in septic ICU patients. DESIGN: Retrospective cohort study. SETTING: Urban academic medical center ICU. PATIENTS: ICU adult patients with severe sepsis or septic shock who had Cl measured on ICU admission were included. Those with baseline estimated glomerular filtration rate less than 15 mL/min/1.73 m or chronic dialysis were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,940 patients included in the study, 615 patients (31.7%) had hyperchloremia (Cl >= 110 mEq/L) on ICU admission. All-cause hospital mortality was the dependent variable. Cl on ICU admission (Cl0), Cl at 72 hours (Cl72), and delta Cl (DeltaCl = Cl72 - Cl0) were the independent variables. Those with Cl0 greater than or equal to 110 mEq/L were older and had higher cumulative fluid balance, base deficit, and Sequential Organ Failure Assessment scores. Multivariate analysis showed that higher Cl72 but not Cl0 was independently associated with hospital mortality in the subgroup of patients with hyperchloremia on ICU admission (adjusted odds ratio for Cl72 per 5 mEq/L increase = 1.27; 95% CI, 1.02-1.59; p = 0.03). For those who were hyperchloremic on ICU admission, every within-subject 5 mEq/L increment in Cl72 was independently associated with hospital mortality (adjusted odds ratio for DeltaCl 5 mEq/L = 1.37; 95% CI, 1.11-1.69; p = 0.003). CONCLUSIONS: In critically ill septic patients manifesting hyperchloremia (Cl >= 110 mEq/L) on ICU admission, higher Cl levels and within-subject worsening hyperchloremia at 72 hours of ICU stay were associated with all-cause hospital mortality. These associations were independent of base deficit, cumulative fluid balance, acute kidney injury, and other critical illness parameters. PMID- 26154936 TI - Epidemiology of biopsy-proven glomerulonephritis in Queensland adults. AB - AIM: There is a paucity of data pertaining to the incidence of biopsy-proven glomerulonephritis (GN) in Australia. This retrospective study aims to review the data from all adult native renal biopsies performed in the state of Queensland from 2002 to 2011--comparing results with centres from across the world. METHODS: Pathology reports of 3697 adult native kidney biopsies were reviewed, of which 2048 had GN diagnoses. Age, gender, clinical indication and histopathology findings were compared. RESULTS: The average age at biopsy was 48 +/- 17 years. Male preponderance was noted overall (~60%), with lupus nephritis being the only individual GN with female predilection. The average rate of biopsy was 12.04 per hundred thousand people per year (php/yr). Nephrotic and nephritic syndromes comprised approximately 75% of all clinical indications that lead to GN diagnoses. IgA nephropathy (1.41 php/yr) was the most common primary GN followed by focal segmental glomerulosclerosis (1.02 php/yr) and crescentic GN (0.73 php/yr). Diabetic nephropathy (0.84 php/yr), lupus nephritis (0.69 php/yr) and amyloidosis (0.19 php/yr) were the most commonly identified secondary GN. CONCLUSION: IgA nephropathy is the predominant primary GN in Queensland, and nephrotic syndrome the most common indication for a renal biopsy. While crescentic GN incidence has significantly increased with time, focal segmental glomerulosclerosis incidence has not shown any trend. Incidence of GN overall appears to increase with age. The annual rate of biopsy in this study appears lower than previously published in an Australian population. PMID- 26154937 TI - Fluorescence microscopy point spread function model accounting for aberrations due to refractive index variability within a specimen. AB - A three-dimensional (3-D) point spread function (PSF) model for wide-field fluorescence microscopy, suitable for imaging samples with variable refractive index (RI) in multilayered media, is presented. This PSF model is a key component for accurate 3-D image restoration of thick biological samples, such as lung tissue. Microscope- and specimen-derived parameters are combined with a rigorous vectorial formulation to obtain a new PSF model that accounts for additional aberrations due to specimen RI variability. Experimental evaluation and verification of the PSF model was accomplished using images from 175-nm fluorescent beads in a controlled test sample. Fundamental experimental validation of the advantage of using improved PSFs in depth-variant restoration was accomplished by restoring experimental data from beads (6 MUm in diameter) mounted in a sample with RI variation. In the investigated study, improvement in restoration accuracy in the range of 18 to 35% was observed when PSFs from the proposed model were used over restoration using PSFs from an existing model. The new PSF model was further validated by showing that its prediction compares to an experimental PSF (determined from 175-nm beads located below a thick rat lung slice) with a 42% improved accuracy over the current PSF model prediction. PMID- 26154938 TI - Combined effect of photobiomodulation with a matrix metalloproteinase inhibitor on the rate of relapse in rats. AB - OBJECTIVE: To investigate combined effect of photobiomodulation with a matrix metalloproteinase (MMP) inhibitor on the relapse rate in relation to MMP expression in rats. MATERIALS AND METHODS: Fifty-two rats were divided into four groups according to the treatment modality: control group, irradiation group, doxycycline group, and irradiation with doxycycline group. During a relapse period of 5 days after orthodontic movement, maxillary central incisors were treated by low-level laser therapy (LLLT) as a photobiomodulation and/or doxycycline as a synthetic MMP inhibitor. Relapse rate was evaluated in association with MMP expression at the gene and protein levels. RESULTS: Relapse rates were increased by LLLT (1.57-fold) and decreased by doxycycline (0.83-fold) compared with the control, showing positive correlation with the levels of expression for all MMPs in the periodontal ligament (PDL). LLLT concomitant with doxycycline administration resulted in no significant differences of relapse rate and MMP expression from the control. CONCLUSIONS: The combined effect of photobiomodulation with an MMP inhibitor around the relapsing teeth proved to be antagonistic to PDL remodeling activity during relapse. This study suggests a basis for developing a novel biologic procedure targeting the MMP-dependent PDL remodeling to control the relapse rate. PMID- 26154939 TI - Immunoassay analysis of proteins in gingival crevicular fluid samples from resorbing teeth. AB - OBJECTIVE: To carry out an immunoassay analysis of biomarkers expressed in gingival crevicular fluid (GCF) with the main goal of finding a useful diagnostic pattern to distinguish between resorbing deciduous teeth and nonresorbing controls. MATERIALS AND METHODS: A split-mouth design was used in this study with a total of 22 GCF samples collected from 11 patients in the mixed dentition. For each child, one deciduous molar with radiographic evidence of root resorption was used as the test tooth whereas the contralateral first permanent molar with formed roots was used as the control tooth. Samples were processed with immunoassays using a panel of selected biomarkers including interleukin-1 beta (IL-1b), interleukin-1 receptor antagonist (IL-1RA), nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase-9 (MMP-9), and dentin sialoprotein (DSP). RESULTS: There were no statistically significant differences in levels of IL-1b, OPG, and MMP-9 between test and control sites (P > .05). IL-1RA was the only biomarker to show a significant down-regulation (P = .04) in GCF samples collected from resorbing teeth. RANKL data showed a heavily skewed distribution and was deemed unreliable. Only one deciduous GCF sample had detectable levels of DSP; therefore, no further statistical calculation was applicable because of the limited amount of data for this biomarker. CONCLUSIONS: This study indicated that IL1-RA is down-regulated in GCF from resorbing primary molars, thus suggesting this cytokine as a potential analyte to be included in a panel that can discriminate between resorbing and nonresorbing teeth. PMID- 26154940 TI - Coupled Space- and Velocity-Focusing in Time-of-Flight Mass Spectrometry-a Comprehensive Theoretical Investigation. AB - A comprehensive theoretical calculation that couples space- and velocity-focusing is developed for optimizing the design of a time-of-flight (TOF) mass spectrometer. Conventional designs for ion sources of TOF mass spectrometers deviate from the optimal condition because the velocity- and space-focusing conditions are considered separately for two ions with simplified equations. The result of a reexamination taking into account all essential ions reveals that the conventional ion source design, especially the length of the ion extraction region, results in poor resolving power. The comprehensive calculation demonstrates that the resolving power increases when the length of the extraction region is shorter than that of the conventional ion source. A numerical analysis indicates that the resolving power dramatically increases when the effective extraction potential compensates for the initial kinetic energy spread of ions. With typically used extraction potentials, the newly optimized ion source improves the resolving power by more than two orders of magnitude compared with the conventional design. This new theoretical interpretation can also be used to predict the optimal extraction potential and extraction delay in conventional ion sources to substantially improve the resolving power. This comprehensive calculation method is effective not only for designing new high-resolution instruments but also for optimizing commercial products. PMID- 26154941 TI - A Phase I Study of the Anti-Idiotype Vaccine Racotumomab in Neuroblastoma and Other Pediatric Refractory Malignancies. AB - BACKGROUND: Pediatric neuroectodermal malignancies express N-glycolylated gangliosides including N-glycolyl GM3 (NeuGcGM3) as targets for immunotherapy. PROCEDURE: We evaluated the toxicity and maximum tolerated dose and immunological response of racotumomab, an anti-idiotype vaccine targeting NeuGcGM3 through a Phase I study enrolling children with relapsed or resistant tumors expressing NeuGcGM3. MATERIALS AND METHODS: Drug dose was escalated to three levels (0.15 0.25-0.4 mg) of racotumomab administered intradermally. Each drug level included three patients receiving a total of three doses, every 14 days. A confirmation cohort was added to the highest dose level. Antibody response was assessed upon study entry and at 4-week intervals for at least three immunological determinations for each patient. RESULTS: Fourteen patients were enrolled (10 with neuroblastoma, one with retinoblastoma, one with Wilms' tumor, and two with brainstem glioma). Three patients completed the three drug levels and three were enrolled in the confirmation cohort. One patient died of tumor progression before completing the three applications. Racotumomab was well tolerated. The only side effect observed was grade 1-2 toxicity at the injection site. Racotumomab elicited an IgM and/or IgG antibody response directed against NGcGM3 in nine patients and IgM against racotumomab in 11 of 13 evaluable patients. The maximum tolerated dose was not reached and no dose-limiting toxicity was seen. CONCLUSIONS: Racotumomab vaccination has a favorable toxicity profile up to a dose of 0.4 mg, and most patients elicited an immune response. Its activity as immunotherapy for neuroectodermal malignancies will be tested in further clinical trials. PMID- 26154942 TI - The mechanism of reduced longitudinal left ventricular systolic function in hypertensive patients with normal ejection fraction. AB - BACKGROUND: MacIver and Townsend's hypothesis predicts, based on a mathematical model of left ventricular contraction, that preserved absolute radial wall thickening (radWT) due to left ventricular hypertrophy is responsible for the normal ejection fraction in patients with heart failure with preserved ejection fraction (HFPEF). METHODS: We tested the validity of this hypothesis by detailed echocardiography including evaluation of ventricular myocardial strain (S) using speckle tracking imaging in at least 60-year-old 18 controls and 94 hypertensive patients with normal ejection fraction. RESULTS: Echocardiography revealed no left ventricular diastolic dysfunction in 38 out of 94 (40%) patients with hypertension (HTDD-negative group), and 56 out of 94 (60%) patients had diastolic dysfunction (HTDD-positive groups). The absolute values of global longitudinal left ventricular peak systolic S were significantly reduced in both patient groups (P < 0.05 for HTDD-negative, P < 0.01 for HTDD-positive groups) vs. the controls. There were no significant between-groups differences in circumferential and radial peak left ventricular systolic Ss, radWT and ejection fraction. Left ventricular mass (LVM) (P < 0.001), LVM/BMI (P < 0.01) increased in the HTDD positive group and ejection fraction/LVM/BMI decreased in both patient groups (P < 0.01 for HTDD-negative, P < 0.001 for HTDD-positive groups) vs. the controls. LVM increased, ejection fraction/LVM/BMI decreased in the HTDD-positive group vs. the HTDD-negative group (P < 0.05 and P < 0.01, respectively). CONCLUSION: We demonstrated decreased longitudinal left ventricular systolic function and showed that preserved ejection fraction was due to preserved absolute radWT and not due to increased radial or circumferential systolic function in patients with hypertension and normal ejection fraction, a potential HFPEF precursor condition. Instead of ejection fraction, rather ejection fraction/LVM/BMI might be used to detect subtle left ventricular systolic dysfunction in hypertension and HFPEF. PMID- 26154943 TI - Studying arterial wall in hypertension. PMID- 26154944 TI - Protein engineering with artificial chemical nucleases. AB - Herein we report the application of oxidative artificial chemical nucleases as novel agents for protein engineering. The complex ion [Cu(Phen)2(H2O)](2+) (CuPhen; Phen = 1,10-phenanthroline) was applied under Fenton-type conditions against a recombinant antibody fragment specific for prostate-specific antigen (PSA) and compared against traditional DNA shuffling using DNase I for the generation of recombinant mutagenesis libraries. We show that digestion and re annealment of single chain variable fragment (scFv) coding DNA is possible using CuPhen. Results indicate recombinant library generation in this manner may generate novel clones-not accessible through the use of DNase I-with CuPhen producing highly PSA-specific binding antibodies identified by surface plasmon resonance. PMID- 26154945 TI - Sudanese (deltabeta)0-Thalassemia: Identification and Characterization of a Novel 9.6 kb Deletion. AB - We report a case of deltabeta-thalassemia (deltabeta-thal) trait in an adult male originally from Sudan. Multiplex ligation-dependent probe amplification (MLPA) was used to localize the approximate boundaries of the deletion, followed by polymerase chain reaction (PCR) amplification and sequence analysis of the junction fragment to determine the precise deletion endpoints. The deletion spans 9594 bp, with the 5' deletion endpoint located 1560 bp upstream of the delta globin gene and the 3' endpoint within the second intervening sequence (IVS-II) of the beta-globin gene. PMID- 26154946 TI - Unfolding of Hydrated Alkyl Diammonium Cations Revealed by Cryogenic Ion Mobility Mass Spectrometry. AB - Hydration of the ammonium ion plays a key role in determining the biomolecular structure as well as local structure of water in aqueous environments. Experimental data obtained by cryogenic ion mobility-mass spectrometry (cryo-IM MS) show that dehydration of alkyl diammonium cations induces a distinct unfolding transition at a critical number of water molecules, n = 21 to 23, n = 24 to 26, and n = 27 to 29, for 1,7-diaminoheptane, 1,8-diaminooctane, and 1,10 diaminodecane, respectively. Results are also presented that reveal compelling evidence for unique structural transitions of hydrated ammonium ions associated with the development of the hydrogen-bond network around individual charged groups. The ability to track the evolution of structure upon stepwise dehydration provides direct insight into the intricate interplay between solvent-molecule interactions that are responsible for defining conformations. Such insights are potentially valuable in understanding how ammonium ion solvation influences conformation(s) of larger biomolecules. PMID- 26154947 TI - Measuring Cognition in Bipolar Disorder with Psychosis Using the MATRICS Consensus Cognitive Battery. AB - Given the substantial overlap in cognitive dysfunction between bipolar disorder (BD) and schizophrenia (SZ), we examined the utility of the MATRICS Consensus Cognitive Battery (MCCB)-developed for use in SZ-for the measurement of cognition in patients with BD with psychosis (BDP) and its association with community functioning. The MCCB, Multnomah Community Ability Scale, and measures of clinical symptoms were administered to participants with BDP (n=56), SZ (n=37), and healthy controls (HC) (n=57). Groups were compared on clinical and cognitive measures; linear regressions examined associations between MCCB and community functioning. BDP and SZ groups performed significantly worse than HC on most neurocognitive domains; BDP and HC did not differ on Social Cognition. Patients with BDP performed better than patients with SZ on most cognitive measures, although groups only differed on social cognition, working memory, verbal memory, and the composite after controlling for clinical variables. MCCB was not associated with community functioning. The MCCB is an appropriate measure of neurocognition in BDP but does not appear to capture social cognitive deficits in this population. The addition of appropriate social cognitive measures is recommended. PMID- 26154948 TI - A 10-year retrospective study of free anterolateral thigh flap application in 872 head and neck tumour cases. AB - The aim of this study was to report the clinical features, reliability, and various applications of free anterolateral thigh (ALT) flaps and to provide a 10 year retrospective review of the application of this flap in head and neck tumour patients. A retrospective study was performed of 872 patients who underwent immediate reconstruction of head and neck tumour-induced defects with ALT flaps between April 2005 and April 2014. The study sample consisted of 609 males and 263 females aged 18-79 years. The shapes and sizes of the flaps were designed individually to meet various demands of reconstruction in the head and neck region. The overall rate of successful reconstruction was 97.4%. The reasons for 57 cases of flap compromise were analyzed. The time to detection of flap crisis was often within the first 8h after surgery (64.9%). One- and two-vein anastomosis strategies in microsurgery were compared, and significant differences were observed in terms of the time to detection of flap compromise and the rate of successful flap salvage. In conclusion, the free ALT flap provides unique features for the reconstruction of oral and facial defects in a reliable and versatile approach. The ALT flap is a favourable and versatile 'workhorse' flap for head and neck reconstruction. PMID- 26154951 TI - Targets, ripples and spirals in a precipitation system with anomalous dispersion. AB - We present a novel reaction-diffusion system that exhibits three-dimensional superdiffusive traveling waves without utilizing any external forces. These waves include single circular targets, spirals, and ripples as well as phase-like waves. The system is based on the interplay of the precipitation reaction of mercuric iodide in a gel medium, its polymorphic transformation to a different crystalline form, and its redissolution in excess iodide. A phase diagram is constructed as a function of the initial concentrations of the reagents. The spatiotemporal evolution of these waves is thoroughly analyzed and seems to be a consequence of an anomalous dispersion relationship. Pattern selection and wavelengths of propagating waves are found to depend on initial concentrations of the reactants. The breakup of the waves is also investigated. While the breakdown of ripples and spirals is shown to be a consequence of a Doppler-like instability in conjunction with anomalous dispersion, the targets undergo a boundary defect mediated breakup. PMID- 26154950 TI - Discrimination of Transgenic Rice containing the Cry1Ab Protein using Terahertz Spectroscopy and Chemometrics. AB - Spectroscopic techniques combined with chemometrics methods have proven to be effective tools for the discrimination of objects with similar properties. In this work, terahertz time-domain spectroscopy (THz-TDS) combined with discriminate analysis (DA) and principal component analysis (PCA) with derivative pretreatments was performed to differentiate transgenic rice (Hua Hui 1, containing the Cry1Ab protein) from its parent (Ming Hui 63). Both rice samples and the Cry1Ab protein were ground and pressed into pellets for terahertz (THz) measurements. The resulting time-domain spectra were transformed into frequency domain spectra, and then, the transmittances of the rice and Cry1Ab protein were calculated. By applying the first derivative of the THz spectra in conjunction with the DA model, the discrimination of transgenic from non-transgenic rice was possible with accuracies up to 89.4% and 85.0% for the calibration set and validation set, respectively. The results indicated that THz spectroscopic techniques and chemometrics methods could be new feasible ways to differentiate transgenic rice. PMID- 26154952 TI - Natural Plasmodium infection in neotropical primates in the island of Sao Luis, state of Maranhao, Brazil. AB - The states that make up the Legal Amazon Region, which include the state of Maranhao, account for 99% of registered cases of human malaria in Brazil. It is also believed that transmission of malaria from nonhuman primates (NHP) to humans occurs in this region, because of current reports of seroepidemiological results from samples from humans and NHP coexisting in the same areas. This study aimed to make morphological, serological and molecular diagnoses of Plasmodium spp. in neotropical primates on the island of Sao Luis, state of Maranhao, Brazil. The diagnostic techniques used were optical microscopy, the polymerase chain reaction (PCR) and the indirect immunofluorescence assay (IFA). From June 2009 to April 2010, 70 NHP were sampled: 50 at the Wild Animal Screening Center (CETAS), located in the municipality of Sao Luis and 20 free-living individuals that were caught in a private reserve located in the municipality of Sao Jose de Ribamar, state of Maranhao. Under an optical microscope, 140 slides (two from each animal) were evaluated and five animals (7.1%) were found to be positive. IFA did not detect anti-Plasmodium spp. From PCR on the 70 animals sampled, amplified Plasmodium spp. products were observed in 13 samples, of which eight (61.5%) were from free-living animals and five (38.5%) were from animals at CETAS. PMID- 26154953 TI - Digenea of Hoplias intermedius and Hoplias malabaricus (Actinopterygii, Erythrinidae) from upper Sao Francisco River, Brazil. AB - A total of 103 specimens of Hoplias intermedius (Gunther, 1864) and 86 specimens of H. malabaricus (Bloch, 1794) from the upper Sao Francisco River, State of Minas Gerais were collected between April 2011 and August 2013, and their parasitic fauna were investigated. Four species of Digenea were found: metacercariae of Austrodiplostomum sp., and Ithyoclinostomum sp.; and adult specimens of Phyllodistomum spatula Odhner, 1902, and Pseudosellacotyla lutzi (Freitas, 1941) Yamaguti, 1954. The prevalence of the metacercariae was higher than that of the adult digeneans of erythrinids from the upper Sao Francisco River as a result of piscivorous feeding habits of these adult erythrinids. The presence of metacercariae and adult digeneans indicate that they act as intermediate and definitive hosts, respectively, in their biological cycles. Hoplias intermedius is a new host for the four species of Digenea, and the Sao Francisco River basin is a new location for the known geographical distributions of P. spatula and P. lutzi. PMID- 26154954 TI - Distribution pattern of crustacean ectoparasites of freshwater fish from Brazil. AB - The purpose of this study was to use the informations relating to parasite crustaceans species that was published over the course of one century (1913 to 2013), in order to search for infestation and distribution patterns among these ectoparasites in Brazilian freshwater fish species. This search was carried out on 445 samples of 119 host fish of 27 families within the orders Characiformes, Perciformes, Clupeiformes, Mugiliformes, Osteoglossiformes, Symbranchiformes, Tetraodontiformes and Siluriformes from various regions of Brazil. We organized different host-parasite systems into matrices grouping species at different taxonomic and infestation levels and according to host parameters. Five families of parasites (Ergasilidae, Argulidae, Lernaeidae, Lernaeopodidae and Cymothoidae) distributed into 76 species of 27 genera were analyzed in the host samples, which presented dominance of Ergasilidae species, mainly from the genus Ergasilus. Some crustaceans are host and site-specific, especially in relation to fish in particular habitats and lifestyles (e.g. Perulernaea gamitanae, Anphira branchialis and Riggia paranensis), while other parasites frequently have no preference (e.g. Lernaea cyprinacea and Braga patagonica). We found broadly similar distribution patterns for some crustacean species among the different localities, whereas other species showed well-defined geographical patterns, and these findings were discussed. PMID- 26154955 TI - New morphological data on Cucullanus pinnai pinnai (Nematoda) parasitizing Pimelodus maculatus (Pimelodidae) in southeastern Brazil. AB - This paper describes the morphology of Cucullanus pinnai pinnai parasitizing Pimelodus maculatus in the Guandu River, Brazil, based on differential interference contrast (DIC) microscopy and scanning electron microscopy (SEM), providing new morphological data about this species of parasite. Nematodes were collected between May and October 2012 from specimens of Pimelodus maculatus in the Guandu River (22 degrees 48'2"S, 43 degrees 37'35"W), in the state of Rio de Janeiro, Brazil. Some characteristics of specimens of Cucullanus in this study fall within the range of morphological variations of previously studied C. pinnai pinnai. Most of the specimens studied here had excretory pore and deirids located at the posterior end of the oesophagus, a feature not recorded in previous studies of this species. In addition, the size of the gubernaculum was larger than the other specimens previously studied. The SEM and DIC analyses of C. pinnai revealed several morphological details of the cephalic region and the tail papillae. With regard to the polymorphism of C. pinnai, morphological and genetic studies of this cucullanid nematode are needed, involving large numbers of host species and a wide geographical distribution. PMID- 26154956 TI - Trichodina modesta: an exotic ciliate in the Neotropical region parasitizing an unusual host. AB - In this study, an important ornamental fish, Betta splendens (Osphronemidae), from three different Brazilian states was examined for parasitic infestations. Smears with parasites were impregnated with silver nitrate or stained using Giemsa for taxonomic evaluation. A disc-shaped trichodinid with a body diameter of 39.7 +/- 3.3 um, adhesive disc diameter of 32.9 +/- 3.1 um and denticulate ring diameter of 19.5 +/- 2.0 um was found. The morphological characteristics resembled those of Trichodina modesta Lom, 1970, a species that shows clear host specificity for Cypriniformes. Until now, its occurrence was restricted to the Eurasian region. In the present study, a new host for T. modesta is reported and therefore the first occurrence of this species in the Americas. The parasite was possibly introduced into the Neotropical region through the exotic fish trade, especially of Cypriniformes used by aquarists. The distribution of this ciliate is discussed and a checklist of localities and hosts for the species is provided. PMID- 26154957 TI - Gastrointestinal nematodes in ostriches, Struthio camelus, in different regions of the state of Rio de Janeiro, Brazil. AB - The ratite group is composed of ostriches, rheas, emus, cassowaries and kiwis. Little research has been done on parasitism in these birds. The aim of this study was to determine the distribution of infections by gastrointestinal nematodes in ostriches in the state of Rio de Janeiro. For this, fecal samples were collected from 192 on 13 farms. From each sample, four grams of feces were used to determine the eggs per gram of feces (EPG) count, by means of the McMaster technique. Part of the feces sample was used for fecal cultures, to identify 100 larvae per sample. The results were subjected to descriptive central trend and dispersion analysis, using confidence intervals at the 5% error probability level in accordance with the Student t distribution, and Tukey's test with a 95% confidence interval. The mean EPG in the state was 1,557, and the municipality of Tres Rios had the lowest average (62). The city of Campos dos Goytacazes presented the highest mean EPG of all the municipalities analyzed. The northern region presented the highest mean EPG, followed by the southern, metropolitan, coastal lowland and central regions. Libyostrongylus species were observed on all the farms: L. douglassii predominated, followed by L. dentatus and Codiostomum struthionis. PMID- 26154958 TI - Prevalence and parasitemia of Haemogregarina sp. in Podocnemis expansa (Testudines: Podocnemididae) from the Brazilian Amazon. AB - Seventy-five turtles Podocnemis expansa in the Brazilian Amazon were examined for the presence of ectoparasites and hemoparasites. Samplings were performed in three study areas in the state of Tocantins, Brazil. Twenty-five specimens were sampled per study area (a commercial breeding facility, an indigenous subsistence breeding facility and a wild population of the Javaes River). Hemoparasites of the genus Haemogregarina were found in 66% (50/75) of the turtle specimens, and the infections were restricted to the commercial breeding facility and to the wild population of the Javaes River. The mean level of parasitemia was 54/2,000 erythrocytes (2%). There was no correlation between the body condition index of the chelonians and the level of parasitemia, with no significant difference between genders. No leeches were observed during the physical exams in any of the study areas, but the specimens from the commercial breeding facility were in poor physical condition with shell deformities and the presence of a relatively high amount of skin ulcerations, most likely caused by fungi and bacteria. This was the first study to record the occurrence of hemogregarines on a population scale in P. expansa and helps to increase knowledge about hemoparasites in chelonians in Brazil. PMID- 26154959 TI - Epidemiology of Megninia spp. in laying flocks from the State of Minas Gerais, Brazil. AB - Aspects related to the epidemiology of Megninia ginglymura were studied, in order to determine predisposing factors for the occurrence in layer chicken houses of commercial farms in the State of Minas Gerais, Brazil. An observational, cross sectional, analytical survey was conducted for identifying major risks or protection factors for infestations. Four hundred thirty-one houses located in forty-three farms were visited in 2012. Regarding the farms, 17 (39.53%) had chickens infested by M. ginglymura and 1 (2.32%) presented Megninia cubitalis. The epidemiological aspects of the occurrence of M. ginglymura were investigated using multiple logistic regression models. The chicken house organization was an important protection factor involved in the occurrence of M. ginglymura (odds ratio [OR] = 0.85). The presence of subsistence breedings of poultry within the premises or at the proximity of a farm was characterized as a risk factor for the occurrence of infestations (OR = 3.92). The use of mineral oil (OR = 0.16) was considered protective against new infestations. Some regions of the state were characterized by a higher risk for mite infestation than others. PMID- 26154960 TI - Infection by Neospora caninum in dairy cattle belonging to family farmers in the northern region of Brazil. AB - Neosporosis is considered a major cause of abortion among cattle worldwide. The aim of this study was to investigate the prevalence of anti-Neospora caninum antibodies in dairy cattle and correlate them with possible risk factors on 63 small farms (family farms) in the municipality of Ji-Parana, the main milk producing region of the state of Rondonia, northern Brazil. For this purpose, 621 serum samples were collected from cows and were evaluated by means of the indirect fluorescence antibody test (IFAT). The overall herd prevalence of N. caninum antibodies among the farms (38/63; 60.31%) showed that N. caninum are widespread among the dairy herds in this region, despite only infecting a small proportion of animals (66/621, 10.62%). Occurrences of abortion and birth of weak calves were the only variables that showed as risk factors for the presence of N. caninum. The result from the spatial lag model strongly indicated that birth of weak calves and presence of N. caninum are occurring on farms that are located close to each other, indicating aggregation of disease occurrence. PMID- 26154961 TI - Morphological and molecular diagnosis of Pseudoterranova decipiens (sensu stricto) (Anisakidae) in imported cod sold in Brazil. AB - An anisakid nematode larva found in cod sold in the state of Minas Gerais, Brazil was studied by light and scanning electron microscopy and by a molecular approach. Mitochondrial cytochrome c-oxidase subunit 2 (mtDNA cox-2), 28S rRNA and ITS1, 5.8S and ITS2 regions were amplified using the polymerase chain reaction and sequenced to evaluate the phylogenetic relationships of the larva. The genetic profile confirmed that this larva belongs to the species Pseudoterranova decipiens (sensu stricto). This is the first molecular and ultrastructural study of Pseudoterranova decipiens (sensu stricto) in imported cod sold in Brazil. The health implications of these findings are discussed. PMID- 26154962 TI - Description of six autochthonous cases of canine visceral leishmaniasis diagnosed in Pedregulho (Sao Paulo, Brazil). AB - Visceral leishmaniasis is an infectious disease of chronic, emerging and zoonotic nature that presents various degrees of severity. In Brazil, this illness is caused by Leishmania infantum (Leishmania chagasi), which is transmitted by the bite of the sand fly Lutzomyia longipalpis, and dogs are its main reservoir. Given the increasing spread of this disease across Brazil, the aim of this study was to report on six cases of canine visceral leishmaniasis, diagnosed in June 2013, in the city of Pedregulho, State of Sao Paulo, considered to be a non endemic area and free of phlebotomine sand flies. The diagnosis was based on clinical signs of the patients and additional tests (serological and parasitological). It was concluded that the diagnosis of leishmaniasis is complex because the clinical signs are similar to other systemic diseases, thus justifying the importance of parasitological test of bone marrow, considered "gold standard", in the confirmation of the disease. In addition, the area was not, until now, considered risk place, despite notification. PMID- 26154963 TI - Conjunctival swab PCR to detect Leishmania spp. in cats. AB - The relevance of the dog as a source of visceral leishmaniasis infection is known, but the role of cats as reservoir hosts for leishmaniasis is not yet fully clear. This study assessed the efficacy of conjunctival swab PCR (CS-PCR) in the detection of cats infected by Leishmania spp. The results were seven (13.5%) cats positive for Leishmania spp. in the PCR, in 52 cats tested from Pirassunuga-SP and Ilha Solteira-SP. From the city of Pirassununga - SP 28.6% (2/7) were positive and from the city of Ilha Solteira - SP 11.1% (5/45) were positive. The results showed that CS-PCR was capable of detecting cats infected by this protozoan. Conjunctival swab samples proved easier to perform in cats, which might facilitate studies on the frequency and distribution of feline leishmaniasis. PMID- 26154964 TI - Comparative study of five techniques for the diagnosis of canine gastrointestinal parasites. AB - Differences in the efficacy of diagnostic techniques employed in the parasitological examination of feces are a limiting factor of this laboratory procedure in the field of Veterinary Parasitology. To verify advances in this type of examination in dogs, we conducted a study using a new technique (TFGII/Dog). Fifty naturally infected dogs were housed in individual stalls, and their feces were evaluated comparatively using this technique and four other conventional techniques. The TFGII/Dog showed high levels of sensitivity and efficiency, surpassing the diagnostic accuracy of the other techniques with a kappa concordance index of 0.739 (Substantial), as opposed to 0.546 (Moderate), 0.485 (Moderate), 0.467 (Moderate), and 0.325 (Fair) of the Spontaneous Sedimentation, Centrifugal-Flotation in Saturated Zinc Sulfate Solution, Centrifugal-Flotation in Saturated Sugar Solution, and Spontaneous-Flotation in Saturated Sodium Chloride Solution techniques, respectively. The combination of positive results of all techniques comprises eight genera of parasites, with Ancylostoma spp. predominating among helminths, and Cystoisospora spp. among protozoa. The TFGII/Dog technique showed better diagnostic performance, and can therefore be considered an important tool for optimizing the results of laboratory routines and for the control of canine gastrointestinal parasites. PMID- 26154965 TI - Echinococcus granulosus sensu lato and Taenia hydatigena in pig in southern Brazil. AB - This study aimed to identify the parasitical etiologic agents of visceral cysts in pigs from the central/northern region of Rio Grande do Sul State, Brazil. Fifty-eight cysts were found in livers during veterinary inspection of swine slaughtered from January 2008 to 2012. Collected samples were submitted to macroscopic and molecular analyzes. Polymerase chain reaction (PCR), DNA sequencing and BLAST alignment of sequences was used to molecular characterization of the samples. By PCR 10.3% (6/58) of tested samples were positive for Echinococcus granulosus sensu lato and 56.9% (33/58) for Cysticercus tenuicollis. In this study, it was verified the occurrence of larval forms of E. granulosus sensu lato and Taenia hydatigena in pig herds from the central/northern region of Rio Grande do Sul State. The presence of both parasites is relevant due to the economic losses for the meat industry. Additionally, E. granulosus sensu lato has zoonotic importance and may be infecting pig herds in southern Brazil. PMID- 26154966 TI - Coccidia of gallinaceous meat birds in Brazil. AB - Coccidiosis is a disease that limits the production and marketing of gallinaceous birds in North America, especially quails, pheasants and chukar partridges. Virtually no research has been conducted in South America on the causative agents of diseases among these birds, including coccidia. The aim of this work was to make first observations on Eimeria spp. in the chukar partridge Alectoris chukar and the grey quail Coturnix coturnix, which are reared for meat in Brazil. Fecal and tissue samples were collected from commercial farms and were examined for oocysts, gross and microscopic lesions or endogenous stages. From this examination, it was found that partridges raised in Brazil did not have any visible infection. However, grey quails presented mild infection and two Eimeria species that had previously been described in other birds were identified. PMID- 26154967 TI - Kudoa spp. (Myxozoa) infection in musculature of Plagioscion squamosissimus (Sciaenidae) in the Amazon region, Brazil. AB - Ninety specimens of Plagioscion squamosissimus captured using fishing tackle in the Outeiro district, state of Para, were examined. Fish were placed in plastic bags containing water, under conditions of artificial aeration, and transported live to the Carlos Azevedo Research Laboratory (LPCA), in Belem, Para. They were anesthetized, euthanized and necropsied; small fragments of the epaxial and hypaxial muscles were removed for examination of fresh histological sections by means of optical microscopy. In 100% of the specimens analyzed, parasitic pseudocysts were seen to be interspersed within and between the skeletal muscle. These contained pseudoquadrate and/or star-shaped spores that presented four valves and four polar capsules, which were identified from their morphology as belonging to the genus Kudoa. This is the first report of Kudoa in P. squamosissimus in the Amazon region, Para, Brazil. PMID- 26154968 TI - Histopathological changes in the kidneys of vertebrate hosts infected naturally and experimentally with Paratanaisia bragai (Trematoda, Digenea). AB - Paratanaisia bragai is a trematode parasite that reaches sexual maturity in the kidney collecting ducts of domesticated and wild fowl and whose intermediate hosts are the snails Subulina octona and Leptinaria unilamellata. There are some discrepancies in descriptions of the pathology of this parasite in bird kidneys. Therefore, the purpose of this study was to analyze the kidneys of rock pigeons (Columba livia) naturally infected and of chickens (Gallus gallus) experimentally infected with Paratanaisia bragai, by means of macroscopic observation and by light and scanning electron microscopy. Both bird species showed significantly dilated collecting ducts. In addition, lymphocyte infiltration was observed in the kidneys of C. livia and metaplasia in the epithelial lining of the kidney collecting ducts of G. gallus. PMID- 26154969 TI - Molecular identification of Hepatozoon canis in dogs from Campo Grande, Mato Grosso do Sul, Brazil. AB - The aim of this study was to investigate the occurrence of Hepatozoon species infecting dogs in the municipality of Campo Grande, Mato Grosso do Sul (MS), Brazil, using blood samples (n = 165) drawn from dogs. The species Hepatozoon canis was identified in 3.63% of the tested animals using molecular tools. Further studies are needed to determine the clinical relevance of this infection and the main arthropod vectors involved in its transmission. PMID- 26154970 TI - Erratum. PMID- 26154971 TI - Erratum. PMID- 26154972 TI - An open-source computational and data resource to analyze digital maps of immunopeptidomes. AB - We present a novel mass spectrometry-based high-throughput workflow and an open source computational and data resource to reproducibly identify and quantify HLA associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies. PMID- 26154973 TI - Identification of polarized macrophage subsets in zebrafish. AB - While the mammalian macrophage phenotypes have been intensively studied in vitro, the dynamic of their phenotypic polarization has never been investigated in live vertebrates. We used the zebrafish as a live model to identify and trail macrophage subtypes. We generated a transgenic line whose macrophages expressing tumour necrosis factor alpha (tnfa), a key feature of classically activated (M1) macrophages, express fluorescent proteins Tg(mpeg1:mCherryF/tnfa:eGFP-F). Using 4D-confocal microscopy, we showed that both aseptic wounding and Escherichia coli inoculation triggered macrophage recruitment, some of which started to express tnfa. RT-qPCR on Fluorescence Activated Cell Sorting (FACS)-sorted tnfa(+) and tnfa(-) macrophages showed that they, respectively, expressed M1 and alternatively activated (M2) mammalian markers. Fate tracing of tnfa(+) macrophages during the time-course of inflammation demonstrated that pro inflammatory macrophages converted into M2-like phenotype during the resolution step. Our results reveal the diversity and plasticity of zebrafish macrophage subsets and underline the similarities with mammalian macrophages proposing a new system to study macrophage functional dynamic. PMID- 26154975 TI - Kinetic Detection of Orthogonal Protein and Chemical Coordinates in Enzyme Catalysis: Double Mutants of Soybean Lipoxygenase. AB - Soybean lipoxygenase-1 (SLO-1) is a paradigmatic enzyme system for studying the contribution of hydrogen tunneling to enzymatic proton-coupled electron transfer processes. In this study, the impact of pairs of double mutants on the properties of SLO-1 is presented. Steady-state rates and their deuterium kinetic isotope effects (KIEs) have been measured for the bimolecular reaction of enzyme with free substrate (kcat/Km) and compared to the unimolecular rate constant, kcat. A key kinetic finding is that the competitive KIEs on the second-order rate constant (kcat/Km) are all reduced from (D)kcat and, despite large changes in rate and activation parameters, remain essentially unaltered under a variety of conditions. These data implicate a protein reaction coordinate that is orthogonal to the chemical reaction coordinate and controls the concentration of the active enzyme. This study introduces a new means to interrogate the alteration of conformational landscapes that can occur following site-specific mutagenesis. PMID- 26154976 TI - Use of psychotropic medications in Sao Paulo Metropolitan Area, Brazil: pattern of healthcare provision to general population. AB - PURPOSE: We estimate the proportion of psychotropic medication use (PMU) among adults in Sao Paulo Metropolitan Area, Brazil. We investigated whether socio demographic factors, comorbidity, and disease severity influence PMU among individuals with psychiatric disorders. METHODS: Data are from the Sao Paulo Megacity Mental Health Survey, a cross-sectional, population-based study, the Brazilian branch of the World Mental Health Survey Initiative. Trained lay interviewers face-to-face assessed psychiatric disorders and PMU through the Composite International Diagnostic Interview. Respondents were asked about use of healthcare service and prescribed medications for mental disorders in the previous year. Information on PMU was collected for 2935 adult residents in the area and among those with disorders who received treatment. RESULTS: Around 6% of respondents reported PMU in the past year: hypnotics or sedatives were used by 3.7% and antidepressants by 3.5%. Among individuals with 12-month disorders, only 14% reported past year PMU. Gender, age, education, income, occupational status, comorbidity, and severity were significant predictors for PMU. Among those with 12-month DSM-IV disorders who obtained treatment in healthcare settings, almost 40% received medication only. Among those treated in specialty mental health service, around 23% received combination of medication and psychotherapy. CONCLUSION: Our study has pointed out that the recent trend of access to mental healthcare in Brazil depicts unmet needs, characterized by a low prevalence of PMU among individuals with psychiatric disorders. Policies that improve appropriate access to prescribed drugs for those most in need are urgent public health priority. PMID- 26154977 TI - The effect of transmitted Er:YAG laser energy through a dental ceramic on different types of resin cements. AB - BACKGROUND AND OBJECTIVE: The laser debonding procedure of adhesively luted all ceramic restorations is based on the ablation of resin cement due to the transmitted laser energy through the ceramic. The purpose of this study was to determine the effect of Er:YAG laser irradiation transmitted through a dental ceramic on five different resin cements. MATERIALS AND METHODS: Five different resin cements were evaluated in this study: G-Cem LinkAce, Multilink Automix, Variolink II, Panavia F, and Rely X Unicem U100. Disc shaped resin cement specimens (n = 10) were fabricated for each group. A ceramic disc was placed between the resin cement discs and the tip of the handpiece of Er:YAG laser device. The resin cement discs were irradiated through the ceramic and the volume of the resin cement discs were measured using a micro-CT system before and after Er:YAG laser irradiation. The volume loss of the resin cement discs was calculated and analyzed with one-way ANOVA and Tukey-HSD tests. RESULTS: The highest volume loss was determined in G-Cem (1.1 +/- 0.6 mm3 ) and Multilink (1.3 +/- 0.1 mm3 ) (P < 0.05) groups, and the lowest volume loss was determined in Rely X (0.3 +/- 0.07 mm3 ), Variolink (0.4 +/- 0.2 mm3 ), and Panavia (0.6 +/- 0.2 mm3 ) groups (P < 0.05). All resin cements were affected by the laser irradiation resulting in the volume loss of the cement; however, there are significant differences among different resin cements. CONCLUSIONS: All the resin cements tested in this study were effected by the Er:YAG laser irradiation and there were significant differences among the resin cements with regard to ablation volume. Lasers Surg. Med. 47:602-607, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26154979 TI - How inhibitory circuits in the thalamus serve vision. AB - Inhibitory neurons dominate the intrinsic circuits in the visual thalamus. Interneurons in the lateral geniculate nucleus innervate relay cells and each other densely to provide powerful inhibition. The visual sector of the overlying thalamic reticular nucleus receives input from relay cells and supplies feedback inhibition to them in return. Together, these two inhibitory circuits influence all information transmitted from the retina to the primary visual cortex. By contrast, relay cells make few local connections. This review explores the role of thalamic inhibition from the dual perspectives of feature detection and information theory. For example, we describe how inhibition sharpens tuning for spatial and temporal features of the stimulus and how it might enhance image perception. We also discuss how inhibitory circuits help to reduce redundancy in signals sent downstream and, at the same time, are adapted to maximize the amount of information conveyed to the cortex. PMID- 26154980 TI - Levels of homology and the problem of neocortex. AB - The neocortex is found only in mammals, and the fossil record is silent on how this soft tissue evolved. Understanding neocortex evolution thus devolves to a search for candidate homologous neocortex traits in the extant nonmammalian amniotes. The difficulty is that homology is based on similarity, and the six layered neocortex structure could hardly be more dissimilar in appearance from the nuclear organization that is so conspicuous in the dorsal telencephalon of birds and other reptiles. Recent molecular data have, however, provided new support for one prominent hypothesis, based on neuronal circuits, that proposes the principal neocortical input and output cell types are a conserved feature of amniote dorsal telencephalon. Many puzzles remain, the greatest being understanding the selective pressures and molecular mechanisms that underlie such tremendous morphological variation in telencephalon structure. PMID- 26154981 TI - New opportunities in vasopressin and oxytocin research: a perspective from the amygdala. AB - In the present review, we discuss how the evolution of oxytocin and vasopressin from a single ancestor peptide after gene duplication has stimulated the development of the vertebrate social brain. Separate production sites became possible with a hypothalamic development, which, interestingly, is triggered by the same transcription factors that underlie the development of various subcortical regions where vasopressin and oxytocin receptors are adjacently expressed and which are connected by inhibitory circuits. The opposite modulation of their output by vasopressin and oxytocin could thus create a dynamic equilibrium for rapid responsiveness to external stimuli. At the level of the individual, nurturing early in life can long-lastingly program oxytocin signaling, maintaining a capability of learning and sensitivity to external stimuli that contributes to development of social behavior in adulthood. Oxytocin and vasopressin are thus important for the development of a vertebrate brain that supports bonding between individuals and building of an interactive community. PMID- 26154978 TI - An integrative model of the maturation of cognitive control. AB - Brains systems undergo unique and specific dynamic changes at the cellular, circuit, and systems level that underlie the transition to adult-level cognitive control. We integrate literature from these different levels of analyses to propose a novel model of the brain basis of the development of cognitive control. The ability to consistently exert cognitive control improves into adulthood as the flexible integration of component processes, including inhibitory control, performance monitoring, and working memory, increases. Unique maturational changes in brain structure, supported by interactions between dopaminergic and GABAergic systems, contribute to enhanced network synchronization and an improved signal-to-noise ratio. In turn, these factors facilitate the specialization and strengthening of connectivity in networks supporting the transition to adult levels of cognitive control. This model provides a novel understanding of the adolescent period as an adaptive period of heightened experience-seeking necessary for the specialization of brain systems supporting cognitive control. PMID- 26154982 TI - Phosphorylation of Tyr245 in the open-inhibited state of Abelson kinase does not induce downstream signaling. AB - Binding of tyrosine kinase inhibitors such as imatinib was shown to induce a novel open-inhibited conformation of BCR-ABL, in which Tyr245 is exposed and prone to phosphorylation. To evaluate whether this leads to priming of the kinase in cellular systems, we probed activation of downstream signaling as a result of Tyr245 phosphorylation in a series of cellular washout experiments. While a spike in Tyr245 phosphorylation was observed both in overexpression and endogenous settings, no induction of downstream signaling was detected, showing that the priming hypothesis is not relevant for the therapeutic situation. PMID- 26154984 TI - WINTER LOVE. PMID- 26154983 TI - Regioselective Control of the SNAr Amination of 5-Substituted-2,4 Dichloropyrimidines Using Tertiary Amine Nucleophiles. AB - The SNAr reaction of 2,4-dichloropyrimidines, further substituted with an electron-withdrawing substituent at C-5, has selectivity for substitution at C-4. Here we report that tertiary amine nucleophiles show excellent C-2 selectivity. In situ N-dealkylation of an intermediate gives the product that formally corresponds to the reaction of a secondary amine nucleophile at C-2. This reaction is practical (fast under simple reaction conditions, with good generality for tertiary amine structure and moderate to excellent yields) and significantly expands access to pyrimidine structures. PMID- 26154985 TI - Nursing and the Aged. PMID- 26154987 TI - IN UNION THERE IS STRENGTH. PMID- 26154986 TI - Thickness dependence of the interfacial Dzyaloshinskii-Moriya interaction in inversion symmetry broken systems. AB - In magnetic multilayer systems, a large spin-orbit coupling at the interface between heavy metals and ferromagnets can lead to intriguing phenomena such as the perpendicular magnetic anisotropy, the spin Hall effect, the Rashba effect, and especially the interfacial Dzyaloshinskii-Moriya (IDM) interaction. This interfacial nature of the IDM interaction has been recently revisited because of its scientific and technological potential. Here we demonstrate an experimental technique to straightforwardly observe the IDM interaction, namely Brillouin light scattering. The non-reciprocal spin wave dispersions, systematically measured by Brillouin light scattering, allow not only the determination of the IDM energy densities beyond the regime of perpendicular magnetization but also the revelation of the inverse proportionality with the thickness of the magnetic layer, which is a clear signature of the interfacial nature. Altogether, our experimental and theoretical approaches involving double time Green's function methods open up possibilities for exploring magnetic hybrid structures for engineering the IDM interaction. PMID- 26154988 TI - Phenolic Components and Antioxidant Activity of Wood Extracts from 10 Main Spanish Olive Cultivars. AB - The chemical composition and radical-scavenging activity of wood samples from 10 main Spanish olive cultivars were studied. The wood samples were collected during the pruning works from trees growing under the same agronomical and environmental conditions. The 10 ethyl acetate extracts were submitted to HPLC-DAD/ESI-MS analysis to determine the phenolic constituents. Seventeen compounds were identified (10 secoiridoids, 3 lignans, 2 phenol alcohols, 1 iridoid, and 1 flavonoid) by comparison with authentic samples. Significant quantitative and qualitative differences were found among olive cultivars. The lignan (+)-1 hydroxypinoresinol 1-O-beta-d-glucopyranoside was the major compound in all olive cultivars, except in cultivars 'Farga' and 'Picual'. The multivariate analysis of all data revealed three sets of cultivars with similar compositions. Cultivars 'Gordal sevillana' and 'Picual' had the most distinct chemical profiles. With regard to the radical-scavenging activity, cultivar 'Picual', with oleuropein as the major phenolic, showed the highest activity (91.4 versus 18.6-32.7%). PMID- 26154989 TI - Hydrothermal Synthesis and Characterization of Novel Brackebuschite-Type Transition Metal Vanadates: Ba2M(VO4)2(OH), M = V(3+), Mn(3+), and Fe(3+), with Interesting Jahn-Teller and Spin-Liquid Behavior. AB - A new series of transition metal vanadates, namely, Ba2M(VO4)2(OH) (M = V(3+), Mn(3+), and Fe(3+)), was synthesized as large single crystals hydrothermally in 5 M NaOH solution at 580 degrees C and 1 kbar. This new series of compounds is structurally reminiscent of the brackebuschite mineral type. The structure of Ba2V(VO4)2(OH) is monoclinic in space group P21/m, a = 7.8783(2) A, b = 6.1369(1) A, c = 9.1836(2) A, beta = 113.07(3) degrees , V = 408.51(2) A(3). The other structures are similar and consist of one-dimensional trans edge-shared distorted octahedral chains running along the b-axis. The vanadate groups bridge across edges of their tetrahedra. Structural analysis of the Ba2Mn(VO4)2(OH) analogue yielded a new understanding of the Jahn-Teller effect in this structure type. Raman and infrared spectra were investigated to observe the fundamental vanadate and hydroxide vibrational modes. Single-crystal temperature-dependent magnetic studies on Ba2V(VO4)2(OH) reveal a broad feature over a wide temperature range with maximum at ~100 K indicating that an energy gap could exist between the antiferromagnetic singlet ground state and excited triplet states, making it potentially of interest for quantum magnetism studies. PMID- 26154990 TI - Triboelectric Charging at the Nanostructured Solid/Liquid Interface for Area Scalable Wave Energy Conversion and Its Use in Corrosion Protection. AB - We report a flexible and area-scalable energy-harvesting technique for converting kinetic wave energy. Triboelectrification as a result of direct interaction between a dynamic wave and a large-area nanostructured solid surface produces an induced current among an array of electrodes. An integration method ensures that the induced current between any pair of electrodes can be constructively added up, which enables significant enhancement in output power and realizes area scalable integration of electrode arrays. Internal and external factors that affect the electric output are comprehensively discussed. The produced electricity not only drives small electronics but also achieves effective impressed current cathodic protection. This type of thin-film-based device is a potentially practical solution of on-site sustained power supply at either coastal or off-shore sites wherever a dynamic wave is available. Potential applications include corrosion protection, pollution degradation, water desalination, and wireless sensing for marine surveillance. PMID- 26154991 TI - Balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension. AB - PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH), especially when severe in patients unsuited for pulmonary endarterectomy, has a poor prognosis. Balloon pulmonary angioplasty (BPA) is a new catheter-based alternative treatment option for patients with inoperable CTEPH. BPA has not been widely accepted, however, primarily because of possible fatal complications, although effects described in 2001 were encouraging. Recent studies about BPA from Japan and Norway are promising. However, this emerging catheter-based intervention is still considered to be experimental because of a number of concerns and unanswered questions. This review describes the recent progress in BPA at the dawn of a new CTEPH treatment era. RECENT FINDINGS: Recent studies about BPA show consistently beneficial effects in haemodynamics, symptoms, 6 minute walking distance, and biomarkers. Exercise capacity and right ventricular function are also improved by BPA. However, this new technique still has potentially fatal complications, including reperfusion oedema and pulmonary artery perforation, even in recent studies. There remain a number of concerns and unanswered questions about BPA, including indications, best procedural approach, and long-term outcomes. SUMMARY: Recent advances in BPA for inoperable CTEPH are promising. Further investigation by multidisciplinary CTEPH teams is mandatory before BPA's role in CTEPH treatment strategies is determined. PMID- 26154993 TI - Similar sound intensity dependence of the N1 and P2 components of the auditory ERP: Averaged and single trial evidence. AB - OBJECTIVE: The literature suggests that the N1 and P2 waves of the auditory ERP are dissociable at the developmental, experimental, and source levels. At the experimental level, inconsistent findings suggest different effects of intensity on the amplitudes of the auditory N1 and P2. Our main goal was to analyze the intensity dependence of the auditory N1 and P2 while controlling for habituation effects. METHODS: We examined the intensity dependence of both averaged and single-trial auditory N1 and P2 waves elicited in a repeated-stimulation protocol. RESULTS: N1 and P2 revealed similar intensity dependence on both standard and filter denoised ERP, with a linear tendency for higher intensities to elicit higher absolute peak amplitudes. At the single-trial level, both waves covary irrespective of stimulus intensity and trial order. CONCLUSIONS: Our results suggest that stimulus intensity variation induces similar effects on both and N1 and P2 and partially contradict previous data that classified the P2 as a non-habituating component. SIGNIFICANCE: Our findings contribute to the ongoing discussion on the functional significance of the auditory P2 deflection. In addition, the present work demonstrated the applicability of a filter denoising method for single-trial estimation in the analysis of the experimental effects on auditory ERP components. PMID- 26154994 TI - A battery-operated portable handheld electrospinning apparatus. AB - Electrospinning (e-spinning) still has certain limitations in flexible practicability because its conventional setup is usually quite bulky and excessively dependent on a plug (electric supply). In this article, we report on a battery-operated e-spinning apparatus (BOEA) based on miniaturization and integration. The new device gets liberated from the conventional heavy power supply, achieves the tight integration of functional parts and can be operated by a single hand due to its small volume (10.5 * 5 * 3 cm(3)) and light weight (about 120 g). Different polymers such as polyvinylpyrrolidone (PVP), polycaprolactone (PCL), polystyrene (PS), poly(lactic acid) (PLA) and poly(vinylidene fluoride) (PVDF) were electrospun into fibers successfully, which confirms the stable performance and good real-time control capability of the apparatus. These results demonstrate that the BOEA could be potentially applied in many fields, especially in biomedical fields such as skin damage, wound healing, rapid hemostasis, etc. PMID- 26154996 TI - Guillain-Barre syndrome. AB - Over the past three decades much has been elucidated about the pathogenesis and clinical manifestations of Guillain-Barre syndrome, the most common cause of acute flaccid paralysis worldwide. Cross-reactivity between surface epitopes on the bacterium Campylobacter jejuni and peripheral nerve gangliosides has been shown to induce antibody-mediated axonal-type neuropathy in some patients. Understanding the molecular mechanisms that cause nerve damage in these patients has led to the development of novel therapies, which specifically target the complement cascade and prevent formation of the membrane attack complex. The most promising, eculizumab, is a humanized monoclonal antibody, which blocks formation of human C5a and C5b-9, and has been shown to prevent antiganglioside antibody induced neuropathy in vitro and in a mouse model and is currently in Phase II clinical trials. PMID- 26154995 TI - Esophageal Squamous Cell Carcinoma and Gastric Cardia Adenocarcinoma Shared Susceptibility Locus in C20orf54: Evidence from Published Studies. AB - This study aimed to determine whether C20orf54 rs13042395 polymorphism modify the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA) in common population. We conducted a systematic literature review and evaluated the quality of included studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated to estimate the strengths of the associations. 9 articles (10 studies) were identified for synthesis analyses. Overall, the results indicated that the C20orf54 rs13042395 genotype was subtly decrease the risk of ESCC (T vs. C: OR = 0.95; 95%CI = 0.90-0.99; P = 0.02) and the rs13042395 polymorphism was associated with a decreased risk of GCA (T vs. C: OR = 0.95; 95%CI = 0.91-0.98; P < 0.01). The subsets were divided by smoking and drinking status, but none of the genetic comparisons reached statistical significance. Subgroup analysis was also stratified by body mass index (BMI), rs13042395 polymorphism was significantly associated with a subtly decreased cancer risk in under-weight group and normal group, but no association was observed in over weight group. In conclusion, C20orf54 rs13042395 polymorphism was significantly associated with decreased ESCC and GCA risk especially for the subjects with under-weight or normal. PMID- 26154997 TI - Knowledge, Attitudes, and Practices of Obstetrician-Gynecologists Regarding Influenza Prevention and Treatment Following the 2009 H1N1 Pandemic. AB - BACKGROUND: Pregnant women are at increased risk for complications associated with influenza. Influenza vaccination during pregnancy helps protect both pregnant women and infants less than 6 months of age from contracting the flu. This study investigated influenza prevention and treatment practices of obstetrician-gynecologists (ob-gyns) during the influenza season immediately following the 2009-2010 H1N1 season. METHODS: In 2011, surveys were sent to two groups of Fellows of the American College of Obstetricians and Gynecologists. Group 1 was 907 ob-gyns who responded to our previous survey on practice and knowledge of influenza vaccination, diagnosis, and treatment during the 2009-2010 H1N1 influenza pandemic. Group 2 was 2,293 new recipients randomly selected from the American College of Obstetricians and Gynecologists database. Data were analyzed in 2013. RESULTS: A high proportion of pregnant patients were reported to be vaccinated against influenza (71.7%); however, the data suggest that in general preventative practices decreased between the 2009-2010 H1N1 season and 2010-2011 season. A higher proportion of women eligible for Medicaid in a practice was associated with a lower estimate of vaccination rate. Ob-gyns with more than 20 years of practice were more likely to be concerned about the risks of antivirals and less likely to routinely prescribe them. CONCLUSIONS: Ob-gyns may be overestimating the proportion of pregnant women being vaccinated. The gains in vaccination and influenza prevention practices from the H1N1 pandemic have not been completely retained. Discrepancies in the use of anti-virals to treat suspected or confirmed influenza in pregnant patients exist and need to be addressed. PMID- 26154998 TI - Seasonal affective disorder in patients with chronic tinnitus. AB - OBJECTIVES/HYPOTHESIS: To investigate the point prevalence of SAD, degrees of anxiety/depression/sleep disturbance, and characteristics of tinnitus in patients with chronic tinnitus. STUDY DESIGN: Cross-sectional survey study. METHODS: From December 2012 to February 2014, 100 patients with chronic persistent or intermittent tinnitus (>3 months) were enrolled. Audiograms, tinnitograms, and Visual Analogue Scales (VAS) were used to assess tinnitus. Tinnitus Handicap Inventory (THI) assessment and questionnaires about anxiety/depression/sleep disturbance/SAD were administered. RESULTS: The male:female ratio was 48:52, and the mean age was 55.0 years. The numbers of patients with suspected SAD and subsyndromal SAD (S-SAD) were nine (9.0%) and 11 (11.0%), respectively. Winter was the most uncomfortable season. Nine patients had a catastrophic THI score >76 (11.1% in the SAD group, 27.3% in the S-SAD group, and 6.3% in the control group), suggesting a significant correlation between SAD/S-SAD and THI (P = .042). Audiogram, tinnitogram, VAS assessment, and sleep disturbance testing revealed no significant differences among the three groups. Anxiety tests yielded more abnormal findings in the SAD group than in the control group (State Anxiety Inventory score: 33.3% vs. 3.3%, respectively, P = .012; Trait Anxiety Inventory score: 22.2% vs. 1.3%, respectively, P = .002). Depression test scores were significantly higher in the SAD/S-SAD groups than in the control group (35.0% vs. 21.3%, respectively; P = .005). CONCLUSIONS: Suspected SAD and/or S-SAD in chronic tinnitus patients were correlated with THI, anxiety, and depression. Understanding SAD in tinnitus patients may be important to manage these patients effectively. LEVEL OF EVIDENCE: 4. PMID- 26154999 TI - The nitration pattern of energetic 3,6-diamino-1,2,4,5-tetrazine derivatives containing azole functional groups. AB - One of the successful strategies for the design of promising new energetic materials is the incorporation of both fuel and oxidizer moieties into the same molecule. Therefore, during recent years, synthesis of various nitro-azole derivatives, as compounds with a more balanced oxygen content, has become very popular. In the framework of this effort, we studied nitration of N(3),N(6) bis(1H-tetrazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine (BTATz; ) and its alkylated derivative N(3),N(6)-bis(2-methyl-2H-tetrazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine , using a (15)N-labeled nitration agent and monitoring and analyzing products of these reactions by (15)N NMR. It was seen that the nitration of both compounds takes place only on the exocyclic ("bridging") secondary amine groups. Possible tetranitro derivative isomers N,N'-(1,2,4,5-tetrazine-3,6-diyl)bis(N-(1-nitro-1H tetrazol-5-yl)-nitramide) and N,N'-(1,2,4,5-tetrazine-3,6-diyl)bis(N-(2-nitro-2H tetrazol-5-yl)nitramide) , both of which have OB = 0% and calculated VODs of 9790 and 9903 m s(-1), respectively, could not be observed in the reaction mixtures, during the in situ(15)N NMR monitoring of nitration of , using (15)N-labeled nitrating agents. Following a similar strategy, a new analog of BTATz - N(3),N(6) Bis(1H-1,2,4-triazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine was obtained and its nitration was studied. The reaction of with a HNO3-Ac2O nitration mixture resulted in the formation of a new N(3),N(6)-bis(3-nitro-1H-1,2,4-triazol-5-yl) 1,2,4,5-tetrazine-3,6-diamine derivative in a moderate yield. Structures and properties of (in the form of its perchlorate salt, ) and were measured by FTIR, multinuclear NMR, MS, DSC and X-ray crystallography. It is important to note that compound exhibits exothermic decomposition at 302 degrees C (DSC) and >353 N (sensitivity to friction), making it a highly-promising thermally-insensitive energetic material for further development. PMID- 26155000 TI - Age- and sex-related reference intervals of lymphocyte subsets in healthy ethnic Han Chinese children. AB - Immunophenotyping of blood lymphocytes has become an important tool in the diagnosis of immunologic and hematologic disorders such as immunodeficiencies, lymphoproliferative and autoimmune diseases. Lymphocyte subsets include total T cells (CD3(+)), TH (T helper, CD3(+) CD4(+)), TC (cytotoxic T cells, CD3(+) CD8(+)), B-cells (CD3(-) CD19(+)), and NK-cells (CD3(-) CD16(+) CD56(+)). Specific lymphocyte subset reference intervals should be locally established for meaningful comparison and to obtain an accurate interpretation of the results. Reference intervals of lymphocyte subsets for Chinese children are scarce. We performed dual-platform flow cytometry to determine the reference intervals of the percentages and absolute counts of lymphocyte subsets, including total T cells, TH cells, TC cells, B-cells, and NK-cells in 1,027 ethnic Han children aged 4 months to 7 years in Henan, China. The children were divided into seven age groups. The percentages and absolute counts differed significantly with age, with the percentages of TH cells and B cells and the CD4/CD8 ratio peaking during the first year, while the percentages of total T cells, TC cells, and NK cells were obviously increased with age; girls showed a trend toward having a higher percentage of TH cells and a higher CD4/CD8 ratio than boys. The absolute counts of lymphocyte subsets peaked during first year and then decreased steadily with age. The reference intervals of lymphocyte subsets among children from China differed from the reported values in Hong Kong, the United States, Cameroon, and Italy. The differences observed could be due to genetic and environmental factors, coupled with the methodology used. The reference intervals of lymphocyte subsets could be used as initial national reference ranges in guidelines for children aged 4 months to 7 years. PMID- 26155001 TI - Toward electron-deficient pyrene derivatives: construction of pyrene tetracarboxylic diimide containing five-membered imide rings. AB - Electron-deficient pyrene-1,2,6,7-tetracarboxylic diimide () and its cyano derivative () have been designed and synthesized as a new family of aromatic diimides. PyrDI has two unexpected five-membered imide rings and can form excimers facilely in the solid state. These new pyrene derivatives are promising n-type semiconductors for organic electronics. PMID- 26155002 TI - Antimicrobial resistance in Vibrio spp. isolated from Canadian imported shrimp, 2009-2014. PMID- 26155003 TI - Clinical response and mortality in tigecycline complicated intra-abdominal infection and complicated skin and soft-tissue infection trials. AB - An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P=1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P=0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio=0.58, 95% confidence interval 0.28-1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies). PMID- 26155005 TI - Spatial analysis of infection by the human immunodeficiency virus among pregnant women. AB - OBJECTIVES: to analyze the spatial distribution of reported cases of pregnant women infected by the human immunodeficiency virus and to identify the urban areas with greater social vulnerability to the infection among pregnant women. METHOD: ecological study, developed by means of spatial analysis techniques of area data. Secondary data were used from the Brazilian National Disease Notification System for the city of Recife, Pernambuco. Birth data were obtained from the Brazilian Information System on Live Births and socioeconomic data from the 2010 Demographic Census. RESULTS: the presence of spatial self-correlation was verified. Moran's Index was significant for the distribution. Clusters were identified, considered as high-risk areas, located in grouped neighborhoods, with equally high infection rates among pregnant women. A neighborhood located in the Northwest of the city was distinguished, considered in an epidemiological transition phase. CONCLUSION: precarious living conditions, as evidenced by the indicators illiteracy, absence of prenatal care and poverty, were relevant for the risk of vertical HIV transmission, converging to the grouping of cases among disadvantaged regions. PMID- 26155004 TI - Effectiveness of papain gel in venous ulcer treatment: randomized clinical trial. AB - OBJECTIVE: to assess the effectiveness of 2% papain gel compared to 2% carboxymethyl cellulose in the treatment of chronic venous ulcer patients. METHOD: randomized controlled clinical trial with 12-week follow-up. The sample consisted of 18 volunteers and 28 venous ulcers. In the trial group, 2% papain gel was used and, in the control group, 2% carboxymethyl cellulose gel. RESULTS: the trial group showed a significant reduction in the lesion area, especially between the fifth and twelfth week of treatment, with two healed ulcers and a considerable increase in the amount of epithelial tissue in the wound bed. CONCLUSION: 2% papain gel demonstrated greater effectiveness in the reduction of the lesion area, but was similar to 2% carboxymethyl cellulose gel regarding the reduction in the amount of exudate and devitalized tissue. Multicenter research is suggested to evidence the effectiveness of 2% papain gel in the healing of venous ulcers. UTN number: U1111-1157-2998. PMID- 26155006 TI - An assessment of primary care attributes from the perspective of female healthcare users. AB - OBJECTIVE: this study sought to assess the quality of the Family Health Strategy (FHS) and investigated the association between primary care attributes (PCAs) and the sociodemographic characteristics of users. METHOD: a total of 215 female FHS users were interviewed for this descriptive and cross-sectional study. The Primary Care Assessment Tool (PCATool), Adult Edition was used, and the results were analyzed using Fisher's exact tests, Pearson's chi-square tests and logistic regressions. RESULTS: the lowest average score corresponded to the dimension "accessibility" (1.80), and the highest score corresponded to "access" (8.76). The results corresponding to the attributes "longitudinality", "coordination", "comprehensiveness", and "orientation" were not significant. No association was found between the participants' sociodemographic characteristics and the essential, derivative, and general attributes (p>0.05). CONCLUSION: several attributes must be improved across all the investigated services from the perspective of female FHS users. PMID- 26155007 TI - Prevalence of Metabolic Syndrome among nursing personnel and its association with occupational stress, anxiety and depression. AB - OBJECTIVE: to identify the prevalence of Metabolic Syndrome among nursing personnel, and its association with occupational stress, anxiety and depression. METHOD: a descriptive correlational study undertaken with 226 nursing personnel from a teaching hospital. Data collection was undertaken through application of the Job Stress Scale, the Hospital Anxiety and Depression Scale and a sociodemographic questionnaire, with variables of Metabolic Syndrome. Univariate analyses and Chi-squared and Pearson tests were used for correlation between the variables, with a level of significance of 5%. RESULTS: 86 (38.1%) workers presented Metabolic Syndrome, of whom 183 (81.1%) were female, and 43 (19.9%) male, aged between 23 and 66 years old. In relation to anxiety and depression, 154 (68.1%) presented anxiety, with 48 (31.2%) also presenting Metabolic Syndrome; 185 (81.8%) presented depression, of whom 62 (33.5%) also had Metabolic Syndrome. It was ascertained that 61 (27.0%) workers presented stress and that of these, 14 (22.9%) presented Metabolic Syndrome. CONCLUSION: a correlation was observed between the variables of anxiety and Metabolic Syndrome and stress and Metabolic Syndrome, there being no correlation between the variables of depression and Metabolic Syndrome. PMID- 26155008 TI - Construction and validation of indicators and respective definitions for the nursing outcome Swallowing Status. AB - OBJECTIVE: to develop indicators for the nursing outcome Swallowing Status and the respective conceptual and operational definitions validated by experts and in a clinical setting among patients after having experienced a stroke. METHOD: methodological study with concept analysis and content and clinical validations. The Content Validation Index was verified for the scores assigned by 11 experts to indicators. Two pairs of nurses assessed 81 patients during the clinical validation: one pair used an instrument with definitions and the other used an instrument without definitions. The resulting assessments were compared using Intraclass Correlation Coefficient, Friedman's test, and Minimal Important Difference calculation. RESULTS: All the indicators, with the exception of the indicator Ability to bring food to mouth, presented Content Validation Index above 0.80. The pair using the instrument with definitions presented an Intraclass Correlation Coefficient above 0.80 for all the indicators and similarity was found in all the assessments, according to the Minimal Important Difference calculation. The pair using the instrument without definitions presented a low coefficient (rho<0.75) for all the indicators. CONCLUSION: the results showed that greater uniformity and accuracy was achieved by the pair of nurses using the conceptual and operational definitions for the indicators of the nursing outcome Swallowing Status. PMID- 26155009 TI - The Living, Dynamic and Complex Environment Care in Intensive Care Unit. AB - OBJECTIVE: to understand the meaning of the Adult Intensive Care Unit environment of care, experienced by professionals working in this unit, managers, patients, families and professional support services, as well as build a theoretical model about the Adult Intensive Care Unit environment of care. METHOD: Grounded Theory, both for the collection and for data analysis. Based on theoretical sampling, we carried out 39 in-depth interviews semi-structured from three different Adult Intensive Care Units. RESULTS: built up the so-called substantive theory "Sustaining life in the complex environment of care in the Intensive Care Unit". It was bounded by eight categories: "caring and continuously monitoring the patient" and "using appropriate and differentiated technology" (causal conditions); "Providing a suitable environment" and "having relatives with concern" (context); "Mediating facilities and difficulties" (intervenienting conditions); "Organizing the environment and managing the dynamics of the unit" (strategy) and "finding it difficult to accept and deal with death" (consequences). CONCLUSION: confirmed the thesis that "the care environment in the Intensive Care Unit is a living environment, dynamic and complex that sustains the life of her hospitalized patients". PMID- 26155010 TI - Impaired gas exchange: accuracy of defining characteristics in children with acute respiratory infection. AB - OBJECTIVE: to analyze the accuracy of the defining characteristics of the Impaired gas exchange nursing diagnosis in children with acute respiratory infection. METHOD: open prospective cohort study conducted with 136 children monitored for a consecutive period of at least six days and not more than ten days. An instrument based on the defining characteristics of the Impaired gas exchange diagnosis and on literature addressing pulmonary assessment was used to collect data. The accuracy means of all the defining characteristics under study were computed. RESULTS: the Impaired gas exchange diagnosis was present in 42.6% of the children in the first assessment. Hypoxemia was the characteristic that presented the best measures of accuracy. Abnormal breathing presented high sensitivity, while restlessness, cyanosis, and abnormal skin color showed high specificity. All the characteristics presented negative predictive values of 70% and cyanosis stood out by its high positive predictive value. CONCLUSION: hypoxemia was the defining characteristic that presented the best predictive ability to determine Impaired gas exchange. Studies of this nature enable nurses to minimize variability in clinical situations presented by the patient and to identify more precisely the nursing diagnosis that represents the patient's true clinical condition. PMID- 26155011 TI - The development of a risk score for unplanned removal of peripherally inserted central catheter in newborns. AB - OBJECTIVE: to develop a risk score for unplanned removal of peripherally inserted central catheter in newborns. METHOD: prospective cohort study conducted in a neonatal intensive care unit with newborn babies who underwent 524 catheter insertions. The clinical characteristics of the newborn, catheter insertion and intravenous therapy were tested as risk factors for the unplanned removal of catheters using bivariate analysis. The risk score was developed using logistic regression. Accuracy was internally validated based on the area under the Receiver Operating Characteristic curve. RESULTS: the risk score was made up of the following risk factors: transient metabolic disorders; previous insertion of catheter; use of a polyurethane double-lumen catheter; infusion of multiple intravenous solutions through a single-lumen catheter; and tip in a noncentral position. Newborns were classified into three categories of risk of unplanned removal: low (0 to 3 points), moderate (4 to 8 points), and high (>= 9 points). Accuracy was 0.76. CONCLUSION: the adoption of evidence-based preventative strategies based on the classification and risk factors faced by the newborn is recommended to minimize the occurrence of unplanned removals. PMID- 26155012 TI - Professional burnout, stress and job satisfaction of nursing staff at a university hospital. AB - OBJECTIVES: to describe the social and work characteristics of the nursing staff at a tertiary hospital in the Public Health Service of Andalucia, to assess the degree of professional professional burnout and job satisfaction of those professionals and to study the possible relation between the professional burnout variables and the stress and job satisfaction levels on the one hand and social and employment variables on the other. METHOD: descriptive and cross-sectional study in a sample of 258 baccalaureate and auxiliary nurses. As research instruments, an original and specific questionnaire was used to collect social and employment variables, the Maslach Burnout Inventory, the Nursing Stress Scale and the Font-Roja questionnaire. Descriptive, inferential statistics and multivariate analysis were applied. RESULTS: average scores were found for professional stress and satisfaction, corresponding to 44,23 and 65,46 points, respectively. As regards professional burnout, an average score was found on the emotional exhaustion subscale; a high score for depersonalization and a low score for professional accomplishment. Studies are needed to identify the scores on these subscales in health organizations and to produce knowledge on their interrelations. PMID- 26155013 TI - Nurses' adherence to the Kangaroo Care Method: support for nursing care management. AB - OBJECTIVE: construct an explanatory theoretical model about nurses' adherence to the Kangaroo Care Method at the Neonatal Intensive Care Unit, based on the meanings and interactions for care management. METHOD: qualitative research, based on the reference framework of the Grounded Theory. Eight nurses were interviewed at a Neonatal Intensive Care Unit in the city of Rio de Janeiro. The comparative analysis of the data comprised the phases of open, axial and selective coding. A theoretical conditional-causal model was constructed. RESULTS: four main categories emerged that composed the analytic paradigm: Giving one's best to the Kangaroo Method; Working with the complexity of the Kangaroo Method; Finding (de)motivation to apply the Kangaroo Method; and Facing the challenges for the adherence to and application of the Kangaroo Method. CONCLUSIONS: the central phenomenon revealed that each nurse and team professional has a role of multiplying values and practices that may or may not be constructive, potentially influencing the (dis)continuity of the Kangaroo Method at the Neonatal Intensive Care Unit. The findings can be used to outline management strategies that go beyond the courses and training and guarantee the strengthening of the care model. PMID- 26155014 TI - Meanings of quality of life held by patients with colorectal cancer in the context of chemotherapy. AB - OBJECTIVE: this study's aim was to interpret the meanings assigned to quality of life by patients with colorectal cancer undergoing chemotherapy. METHOD: the ethnographic method and the medical anthropology theoretical framework were used. Data were collected through semi-structured interviews and participant observations with 16 men and women aged from 43 to 75 years old undergoing chemotherapy in a university hospital. RESULTS: the meanings and senses describe biographical ruptures, loss of normality of life, personal and social suffering, and the need to respond to chemotherapy's side effects; chemotherapy is seen as a transitional stage for a cure. Quality of life is considered unsatisfactory because the treatment imposes personal and social limitations and QoL is linked to resuming normal life. CONCLUSIONS: the meanings show the importance of considering sociocultural aspects in the conceptualization and assessment of quality of life. PMID- 26155015 TI - Use and influence of Delivery and Birth Plans in the humanizing delivery process. AB - OBJECTIVES: get to know, analyze and describe the current situation of the Delivery and Birth Plans in our context, comparing the delivery and birth process between women who presented a Delivery and Birth Plan and those who did not. METHOD: quantitative and cross-sectional, observational, descriptive and comparative cohort study, carried out over two years. All women who gave birth during the study period were selected, including 9303 women in the study. RESULTS: 132 Delivery and Birth Plans were presented during the first year of study and 108 during the second. Among the variables analyzed, a significant difference was found in "skin to skin contact", "choice of dilation and delivery posture", "use of enema", "intake of foods or fluids", "eutocic deliveries", "late clamping of the umbilical cord" and "perineal shaving". CONCLUSIONS: the Delivery and Birth Plans positively influence the delivery process and its outcome. Health policies are needed to increase the number of Delivery and Birth Plans in our hospitals. PMID- 26155017 TI - Luminescent Mechanochromism in a Gold(I)-Copper(I) N-Heterocyclic Carbene Complex. AB - The silver(I) species [Ag(benzim(CH2py)2)2]PF6 (1) was prepared by refluxing the ligand precursor [H(benzim(CH2py)2)2]PF6 with Ag2O and aqueous sodium hydroxide in dichloromethane. Simple transmetalation of 1 with tetrahydrothiophenegold(I) chloride forms the gold(I) analogue [Au(benzim(CH2py)2)2]PF6 (2). The addition of 2 equiv of [Cu(NCCH3)4]PF6 to 2 in acetonitrile produces a blue-luminescent, trimetallic complex, [AuCu2(benzim(CH2py)2)2(NCCH3)4](PF6)3.2CH3CN (3.2CH3CN). When blue-luminescent 3.2CH3CN is exposed to air, the complex loses four acetonitrile molecules, and the emission of the desolvated complex (4) appears aquamarine. Crystallization of 4 from different solvents produces the complexes [AuCu2(benzim(CH2py)2)2](PF6)3 (5) and [AuCu2(benzim(CH2py)2)2(NCCH2CH3)2](PF6)3 (6). Upon grinding, both 3.2CH3CN and 4 exhibit mechanochromic transformations to a yellow-luminescent powder (ground-4). The reversible mechanochromic transformation of 3.2CH3CN to ground-4 is a crystalline-to-amorphous conversion accompanied by partial desolvation. The luminescent mechanochromism of 4 to ground-4 is an "amorphous-to-amorphous" process and does not require solvent loss. In addition to their mechanochromic properties, both 3.2CH3CN and 4 exhibit luminescent thermochromism through desolvation to form a weak luminescent powder (7). PMID- 26155016 TI - Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-A resolution. AB - Hepatitis C virus (HCV), a widespread human pathogen, is dependent on a highly structured 5'-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation of all of its proteins. The HCV IRES initiates translation by directly binding to the small ribosomal subunit (40S), circumventing the need for many eukaryotic translation initiation factors required for mRNA scanning. Here we present the cryo-EM structure of the human 40S ribosomal subunit in complex with the HCV IRES at 3.9 A resolution, determined by focused refinement of an 80S ribosome-HCV IRES complex. The structure reveals the molecular details of the interactions between the IRES and the 40S, showing that expansion segment 7 (ES7) of the 18S rRNA acts as a central anchor point for the HCV IRES. The structural data rationalizes previous biochemical and genetic evidence regarding the initiation mechanism of the HCV and other related IRESs. PMID- 26155020 TI - Managing premature menopause and sexual dysfunction. AB - PURPOSE OF REVIEW: Young women (<45 years of age) diagnosed with breast cancer face increased risk of sexual dysfunction as a result of their cancer-directed treatment. We will review the recent literature examining this critical challenge and discuss current efforts to address sexual dysfunction. RECENT FINDINGS: In the period since 2013, the literature has focused on sexual issues that result from the premature onset of menopausal symptoms and changes in sexual health following breast surgery. The impact of premature menopause in young women with breast cancer is profound and can affect all aspects of the sexual experience, from desire to function, and quality of life. Furthermore, the surgical treatment of breast cancer also has significant implications with respect to sexual desire and body image. There is a paucity of sexual health intervention for this population, though recent efforts suggest that sexual health outcomes may be improved if women are offered the appropriate intervention opportunities. However, the sexual function of young breast cancer patients is an under discussed and under-treated health issue that warrants greater research and clinical focus. SUMMARY: Further intervention trials must be completed in this population of young women for whom sexual function plays such a critical role in their personal and relationship well being. PMID- 26155021 TI - Palliative systemic therapy for young women with metastatic breast cancer. AB - PURPOSE OF REVIEW: Breast cancer in young women age less than 40 years remains a relatively rare disease. Emerging data suggest that the biology of breast cancer in younger women may differ from that of older women. Although metastatic breast cancer remains incurable, it is definitely treatable; especially in this era of emerging novel therapeutics. RECENT FINDINGS: Most women have hormone receptor positive disease and strategies that interfere with proliferation and the PI3 kinase pathway are reporting exciting results. The prognosis of the metastatic HER2 subtype has been extended to a median survival of 56 months with dual HER2 targeting agents in the first-line setting. Finally, triple negative breast cancer has an enlarging range of therapeutic options including immunotherapy, antiangiogenesis therapy, and targeted therapies including agents that interfere with androgen receptor signaling. SUMMARY: Combined palliative and holistic approaches are essential to help young women navigate the marathon of treatment for metastatic breast cancer. PMID- 26155022 TI - Commentary to 'Reliance of preoperative scrotal examination versus final operative findings in the evaluation of non-palpable testes'. PMID- 26155023 TI - Texas Nurses Set Guidelines for Nurses Serving as Consultants to Nursing Homes. PMID- 26155024 TI - KNOW YOUR COMMUNITY RESOURCES. PMID- 26155025 TI - Academic Progression for Associate Degree Nursing Students: Evolution, Not Revolution. PMID- 26155026 TI - Easing the Transition From Clinician to Nurse Educator: An Integrative Literature Review. AB - BACKGROUND: Experienced clinicians who choose to become academic nurse educators bring to their new faculty role strong clinical skills and a desire to influence the next generation of nurses. However, many find themselves unprepared for the challenges they encounter. Intentional mentoring is needed to ease their transition from clinician to nurse educator. METHOD: An integrative literature review was conducted to identify the essential components of a comprehensive mentoring program to facilitate a positive transition experience from expert clinician to novice nursing faculty. Searches were conducted of the ProQuest Central and CINAHL databases for peer-reviewed articles. RESULTS: A review of 17 publications and seven Web sites identified formal preparation for teaching, guidance navigating the academic culture, and a structured mentoring program as essential to clinicians' successful transition to academic nursing faculty. CONCLUSION: Sustainable mentoring programs require recognition of mentoring as central to nursing education and administrative investment of resources. PMID- 26155027 TI - Leadership Curricula in Nursing Education: A Critical Literature Review and Gap Analysis. AB - BACKGROUND: The Institute of Medicine's Future of Nursing report advises nursing education programs to integrate and embed leadership content within all areas of prelicensure nursing curriculum. This critical literature review synthesizes the state of the science of leadership curricula in prelicensure baccalaureate nursing education programs from 2008 to 2013. Gaps are identified and discussed. METHOD: The Academic Search Premier and Health Source databases were searched, using the keywords baccalaureate nursing education and leadership. The CINAHL database was searched, using the keywords leadership, education, nursing, and baccalaureate. RESULTS: The 13 peer-reviewed articles identified for inclusion comprised descriptive articles (n = 8), mixed-methods studies (n = 2), quantitative studies (n = 2), and a qualitative study (n = 1). CONCLUSION: The underlying theme identified is the study and use of active learning strategies. Subthemes within this context were the use of reflection, peer learning, interdisciplinary teams, organizational partnerships, and curricular reform. PMID- 26155028 TI - Academic and Institutional Review Board Collaboration to Ensure Ethical Conduct of Doctor of Nursing Practice Projects. AB - BACKGROUND: Navigating the regulations to protect human subjects and private health information for Doctor of Nursing Practice (DNP) projects can be a formidable task for students, faculty, and the institutional review board (IRB). METHOD: Key stakeholders from the University of Iowa College of Nursing and the Human Subjects Office developed a standardized process for DNP students to follow, using a decision algorithm, a student orientation to the human subjects review process conducted by faculty and IRB chairs and staff, and a brief Human Subjects Research Determination form. RESULTS: Over 2 years, 109 students completed the process, and 96.3% of their projects were deemed not to be human subjects research. Every student submitted documentation of adherence to the standardized process. Less time was spent by students, faculty, and the IRB in preparing and processing review requests. CONCLUSION: The interprofessional collaboration resulted in a streamlined process for the timely review of DNP projects. PMID- 26155029 TI - Undergraduate Nursing Students' Experience of Service-Learning: A Phenomenological Study. AB - BACKGROUND: Service-learning programs are becoming more evident in baccalaureate nursing curriculums. Anecdotal evidence describing student perceptions has been written; however, research has not been conducted regarding the in-depth student experience of service-learning with vulnerable populations in inner cities. METHOD: This study was conducted using Colaizzi's descriptive phenomenological method of inquiry. Through purposeful sampling, 10 students were interviewed who have participated in service-learning throughout their sophomore, junior, and senior years of nursing education. RESULTS: Five themes were identified Shattering Stereotypes, Overwhelmed With Their Need, Transitioning to Community Caregiver, Advocating, and Reciprocal Benefits-and a fundamental structure emerged. CONCLUSION: Listening to the voices of students participating in service learning enables educators to gain an in-depth perspective of their experience and, ultimately, to maximize the service-learning program and improve care delivered to this vulnerable inner city population. PMID- 26155030 TI - Dedicated Education Units: Partnerships for Building Leadership Competency. AB - BACKGROUND: To enable nurses to lead in health care transformation, nursing education must include opportunities for developing leadership, as well as clinical competencies. Dedicated education units (DEUs) provide supportive environments for competency development in undergraduate students. This study's aim was to explore the effects of a DEU experience on the leadership development of baccalaureate nursing students. METHOD: A mixed-methods design included a quantitative strand, using a quasi-experimental, pretest-posttest, multisite design with control groups and a qualitative strand using focus groups. RESULTS: Students in the DEUs demonstrated significant increases (p < 0.01) in leadership behaviors, as measured by the Student Leadership Practice Inventory. Focus group themes illuminate how the experiences of the students contributed to their leadership growth. CONCLUSION: Findings suggest that the DEU experience may promote enhanced undergraduate leadership competency development. PMID- 26155031 TI - Nurse Practitioner Students Learning From the Medically Underserved: Impact on Attitude Toward Poverty. AB - BACKGROUND: With no antecedent in the literature, this project examined the effects of exposure to clients living in poverty on nurse practitioner (NP) students' attitude toward poverty. METHOD: Students participating in adult health courses completed the Attitude Toward Poverty Scale at the start and end of the course. Eight students were immersed for a minimum of 32 hours with a faculty preceptor in a clinic caring for low-income, uninsured patients. These students also responded to open-ended questions regarding their experience. RESULTS: NP students had an increase in positive attitude toward impoverished patients after the course (p < 0.001). Themes that emerged from the immersion experience were (a) misconception, (b) lack of knowledge about cost and access to care, (c) importance of the clinical environment on learning to be an NP, and (d) empowerment. CONCLUSION: Planned clinical rotations with medically underserved populations may serve to dispel misconceptions about low-income patients. PMID- 26155032 TI - Impact of Integrating Community-Based Participatory Research Into a Baccalaureate Nursing Curriculum. AB - BACKGROUND: Community-based participatory research (CBPR) is rapidly gaining respect within the health care community as a means to promote public health and address health disparities. It has also recently been named as one of the competencies needed by public health professionals to be effective. METHOD: This article describes an educational innovation where CBPR is integrated into a baccalaureate nursing curriculum as a strategy to create meaningful learning experiences for nursing students while benefitting the health of the community. RESULTS: The impact of this approach was analyzed over a period of 12 years. The positive outcomes for the community, students, and faculty are described, along with the unique challenges. CONCLUSION: Integrating CBPR into a nursing curriculum is an innovation that is worthy of further assessment. PMID- 26155033 TI - Five Steps to Providing Effective Feedback in the Clinical Setting: A New Approach to Promote Teamwork and Collaboration. AB - BACKGROUND: Feedback is a major component of clinical education. Feedback reinforces or modifies behavior and helps learners to validate knowledge and feel motivated to learn. Traditionally, feedback is used by clinical educators who observe learners' behavior and provide expert direction. Teamwork and collaboration is one of the six Quality and Safety Education for Nurses core competencies developed for prelicensure and graduate nurses. These skills are important in the current complex health care environment. METHOD: On the basis of the literature and prior experience, a new approach for clinical educators is using feedback to teach teamwork and collaboration skills. RESULTS: Five steps educators can take to provide effective feedback in the clinical setting are to (a) create a culture of feedback, (b) use structured communication tools, (c) encourage dialogue, (d) acknowledge the human factor, and (e) embrace a leadership role. CONCLUSION: This new approach enhances feedback and teaches teamwork and collaboration. PMID- 26155034 TI - Resolving Bottlenecks: Converting Three High-Enrollment Nursing Courses to an Online Format. AB - BACKGROUND: Converting large undergraduate classes from the classroom to online has been an effective way to increase enrollments in high-demand courses in undergraduate education. However, challenges exist to maintaining students' high quality learning interaction and engagement in large online courses. This article presents a collaborative model between faculty in health sciences and instructional designers to redesign and redevelop three high-enrollment courses to online at Boise State University. METHOD: Health studies course faculty and eCampus instructional designers conducted this study to reflect the collaborative online course development process at Boise State. RESULTS: The offering of high enrollment nursing courses met enrollment demand and maintained student retention. Challenges related to instruction were addressed by using a careful course redesign process and continuous improvement. CONCLUSION: Implications of this educational innovation for health science educators, instructional designers, and lessons learned are provided. PMID- 26155035 TI - Mapping HIV Nursing Core Competencies in Entry-Level Education: A Pilot Project. AB - BACKGROUND: Many nursing specialty groups in Canada have developed their own entry-to-practice frameworks to inform nursing curricula. This article focuses on the framework of HIV/AIDS core competencies developed by the Canadian Association of Nurses in HIV/AIDS Care. METHOD: The goal of this pilot project was to map the courses offered in one entry-level program to assess the applicability of the framework as a tool to inform curriculum development. RESULTS: This project highlighted competencies that were well covered in the current courses offered in the program, as well as existing gaps. To address these gaps, five areas of improvement were identified. CONCLUSION: The gaps and areas of improvement identified in this project are similar those identified in the nursing literature. As such, they reinforce the importance of incorporating education and training in entry-level programs with actual clinical experiences with and exposure to people living with HIV. PMID- 26155036 TI - Care on a Continuum: Interactive Role-Playing Scenarios for Undergraduate Women's Health Students. PMID- 26155037 TI - Editorial. PMID- 26155038 TI - Isolation and Expansion of Hepatic Stem-like Cells from a Healthy Rat Liver and their Efficient Hepatic Differentiation of under Well-defined Vivo Hepatic like Microenvironment in a Multiwell Bioreactor. AB - BACKGROUND: Currently, undifferentiated cells are found in all tissue and term as local stem cells which are quiescent in nature and less in number under normal healthy conditions but activate upon injury and repair the tissue or organs via automated activating mechanism. Due to very scanty presence of local resident somatic local stem cells in healthy organs, isolation and expansion of these adult stems is an immense challenge for medical research and cell based therapy. Particularly organ like liver, there is an ongoing controversy about existence of liver stem cells. METHODS: Herein, Hepatic stem cells population was identified during culture of primary hepatocyte cells upon immediate isolation of primary hepatocyte cells. These liver stem cells has been expanded extensively and differentiated into primary hepatocytes under defined culture conditions in a nanostructured self assembling peptides modular bioreactor that mimic the state of art of liver microenvironment and compared with Matrigel as a positive control. Nanostructured self assembling peptides were used a defined extracellular matrix and Matrigel was used for undefined extracellular matrix. Proliferation of hepatic stem cells was investigated by two strategies. First strategy is to provide high concentration of hepatocyte growth factor (HGF) and second strategy is to evaluate the role of recombinant human erythropoietin (rHuEPO) in presence of trauma/ischemia cytokines (IL-6, TNF-alpha). Expansion to hepatic differentiation is observed by morphological analysis and was evaluated for the expression of hepatocyte-specific genes using RT-PCR and biochemical methods. RESULTS: Hepatocyte-specific genes are well expressed at final stage (day 21) of differentiation period. The differentiated hepatocytes exhibited functional hepatic characteristics such as albumin secretion, urea secretion and cytochrome P450 expression. Additionally, immunofluorescence analysis revealed that hepatic stem cells derived hepatocytes exhibited mature hepatocyte markers (albumin, CK-19, CPY3A1, alpha 1-antitrypsin). Expansion and hepatic differentiation was efficiently in nanostructured self assembling peptides without such batch to batch variation while there was much variation in Matrigel coated bioreactor. In conclusion, the results of the study suggest that the nanostructured self assembling peptides coated bioreactor supports expansion as well as hepatic differentiation of liver stem cells which is superior than Matrigel. CONCLUSION: This defined microenvironment conditions in bioreactor module can be useful for research involving bioartificial liver system, stem cell research and engineered liver tissue which could contribute to regenerative cell therapies or drug discovery and development. PMID- 26155039 TI - Rapid Reversal of Liver Steatosis With Life Style Modification in Highly Motivated Liver Donors. AB - BACKGROUND: Liver steatosis is the leading cause of donor rejection in living donor liver transplantation. Rapid weight loss is difficult to achieve in a short period of time, moreover it has been thought to worsen liver histology. METHODS: Donors who had significant steatosis based on liver biopsy were recommended 1200 Kcal/day and a minimum of 60 min/day moderate cardio training. Two patients were advised statins for dyslipidemia. None of the donors had metabolic syndrome. A second ultrasound guided liver biopsy was done at 28 +/- 10 days. Donors with nonalcoholic steatohepatitis/fibrosis or >30% steatosis were not included. RESULTS: From July 2010 to January 2015, 16 donors were advised aggressive life style modification after initial biopsy; 15 (10 males, age 27.5 +/- 6.5 years, baseline body mass index 28.4 +/- 2.1 Kg/M(2)) successfully reduced weight and 14 underwent donation after favorable second biopsy. Mean weight loss was 7 +/- 4.3 kg (8.4 +/- 4.6%). Second liver biopsy was done at 28 +/- 10 days, there was decrease in steatosis in all but one including normalization of liver biopsy in 7 donors. Three donors had mild inflammation on first biopsy and they had improvement in second biopsy. All the donors and their recipients had an uneventful post-operative course. CONCLUSION: Steatosis can be reversed in a short duration by aggressive life style modifications in highly motivated liver donors. PMID- 26155040 TI - Online-to-print Lags and Baseline Number of Citations in 5 Science Citation Index Journals Related to Liver Diseases (2013-2014). AB - OBJECTIVES: To analyze the length of online-to-print lags in 5 science citation index (SCI) journals related to liver diseases and their effect on the number of citations at the date of print publication. DESIGNS: All original papers that were published between April 2013 and April 2014 in 5 SCI journals of liver diseases were systematically collected. The length of the online-to-print lag was defined as the difference between the date of print publication and the date of online publication. The number of citations for an article was obtained on its print publication date (baseline number of citations) and every month thereafter. According to the 2012 journal impact factor (JIF), the journals were divided into high-JIF (JIF >=5) and low-JIF (JIF <5). RESULTS: During the collection period, a total of 1039 original articles were published in the 5 journals. The low-JIF journals had significantly longer online-to-print lags than the high-JIF journals (6.23 +/- 2.9 months versus 4.3 +/- 1.5 months, P < 0.001). The low-JIF journals had a significantly larger proportion of original articles with a baseline number of citations >=1 than the high-JIF journals (41.9% versus 32.3%, P = 0.002). A longer online-to-print lag was positively associated with a baseline number of citations >=1 in all 5 journals. CONCLUSIONS: Online-to-print lags are frequently observed in 5 SCI journals related to liver diseases. In contrast to the hypothesis that JIF was positively associated with the length of online-to-print lags, our study demonstrated that the low-JIF journals had significantly longer online-to-print lags than the high-JIF journals. PMID- 26155041 TI - Most Patients of Hepatitis C Virus Infection in India Present Late for Interferon Based Antiviral Treatment: An Epidemiological Study of 777 Patients from a North Indian Tertiary Care Center. AB - BACKGROUND: Interferon-based antiviral therapy is offered only to those HCV patients who have either chronic hepatitis or early cirrhosis. Advanced cirrhotics do not tolerate interferon-based therapy. Since HCV is asymptomatic in early stages and usually presents late, the eligibility for interferon-based therapy is thus limited. There are scarce studies from India, which looked specifically the eligibility of interferon-based therapy in HCV patients. AIM: To study the spectrum of presentation of HCV infection, determine their eligibility for interferon-based therapy, and follow for SVR. METHODS: The records of all consecutive patients of HCV, >14 years age, who presented to our department between 2008 and 2014, were analyzed for categorization into chronic hepatitis, cirrhosis and hepatocellular carcinoma. Patients with detectable HCV RNA who have chronic hepatitis or Child A cirrhosis were considered eligible for Peg interferon and ribavirin. Patients who received treatment were followed for SVR. RESULTS: 777 patients (median age 49 [range 15-95] years, males 69%) were included. Cirrhosis was the most common presentation (56%, 439/777) followed by chronic hepatitis (37%, 287/777) and HCC (7%, 51/777). Of patients who had cirrhosis (including those with HCC), 36% (174/490) were Child A; 51% (250/490) were Child B and 14% (66/490) were Child C. Only 347/777 (45%) were eligible for Peg-interferon-alpha and Ribavirin. Among the remaining 430 patients, in 326 (76%) the disease was far too advanced. Of eligible patients only 54% actually received Peg-interferon-alpha and Ribavirin and 81% patients could complete the course. Of them only 70% could achieve SVR. CONCLUSIONS: Most HCV patients in India present late and only about 45% are eligible for Interferon-based antiviral treatment. At presentation 56% patients already have cirrhosis and 7% have HCC. Since HCV is usually asymptomatic in early stages, awareness about screening should be increased so that more patients are diagnosed early before they develop cirrhosis or HCC. PMID- 26155042 TI - Could Stem Cell Therapy be the Cure in Liver Cirrhosis? AB - Over the past five decades, liver cirrhosis has become an increasingly prevalent disease and one that will often require considerable medical intervention. However, current treatment options have demonstrated severe problems that have prompted research to provide a suitable alternative. These treatments are scarcely available, very expensive and present at a huge cost to the patient's quality of life. The introduction of stem cell therapy into liver disease has been heralded as the future of personalized medicine and may be the alternative that the healthcare system desperately seeks. To truly determine the scientific basis surrounding this excitement, a literature search was carried out in January 2013 to determine all the data that was present in this topic area. All articles also underwent full cross-referencing to ensure no data was missed. 11 clinical trials were found to meet this criteria and trials were included in both English and non-English languages. The sporadic nature of the data across the trials, with various methods and stem cell types, made comparisons difficult. The basic trends from the data were positive and the majority deemed the use of stem cells safe and feasible in patients presenting with cirrhotic liver disease. However, there is a clear requirement for more research, not only to determine the most efficacious technique and stem cell type but also to further understand stem cells to enhance progress. There may also be a requirement for a framework that future stem cell trials can be based on, which would allow future data to be comparative and allow valid conclusions to be drawn which may propel this therapy into standard clinical practice. PMID- 26155044 TI - Primary Hepatic Burkitt Lymphoma: A Bizarre Site and Triumph Tale. AB - Primary hepatic Burkitt lymphoma (PHBL) is an extremely rare form extra nodal lymphoma and till now only 11 case reports have been found in the literature. We are reporting an adult female with primary hepatic Burkitt's lymphoma, who achieved complete remission after 5 months of combination chemotherapy containing vincristine, cyclophosphamide, doxorubicin, methotrexate, prednisolone and intrathecal chemotherapy. She is under regular follow up at our institute. PMID- 26155045 TI - Hepatocellular Carcinoma Without Cirrhosis Presenting With Hypercalcemia: Case Report and Literature Review. AB - BACKGROUND: Hepatocellular carcinoma (HCC) in non-cirrhotic livers is an uncommon finding and can present insidiously in patients. Another uncommon finding in HCC, and one of poor prognosis, is the presence of paraneoplastic diseases such as hypercalcemia. We report a case of a 66-year-old previous healthy Filipina woman who after routine laboratory evaluation was discovered to have hypercalcemia as the first sign of an advanced HCC without underlying cirrhosis. Because of the patient's relative lack of symptoms, healthy liver function, lack of classical HCC risk factors, and unexpected hypercalcemia, the diagnosis of a paraneoplastic syndrome caused by a noncirrhotic HCC was unanticipated. METHODS: Case Analysis with Pubmed literature review. RESULTS: It is unknown how often hypercalcemia is found in association with HCC in a non-cirrhotic liver. However, paraneoplastic manifestations of HCC, particularly hypercalcemia, can be correlated with poor prognosis. For this patient, initial management included attempts to lower calcium levels via zoledronate, which wasn't completely effective. Tumor resection was then attempted however the patient expired due to complications from advanced tumor size. CONCLUSIONS: Hypercalcemia of malignancy can be found in association with non-cirrhotic HCC and should be considered on the differential diagnosis during clinical work-up. PMID- 26155046 TI - Role of Pentoxifylline and Steroids for Alcoholic Hepatitis - Has the last word been said? PMID- 26155043 TI - The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis. AB - Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed. PMID- 26155048 TI - Recurrent Budd-Chiari Syndrome Presenting with Lower Limb Ulcers. PMID- 26155047 TI - Hepatobiliary Quiz (Answers)-14 (2015). PMID- 26155049 TI - Evaluation of functional outcome and complications of locking calcaneum plate for fracture calcaneum. AB - BACKGROUND: Open reduction and internal fixation (ORIF) is the treatment of choice for displaced intra-articular calcaneal fracture at many orthopaedic trauma centres. In this prospective study, we evaluated the functional outcome and complications of locking compressive calcaneum plate for displaced intra articular fracture calcaneum. METHODS: Between October 2011 and March 2012, 30 patients with displaced intra-articular fracture calcaneum attending the outdoor and emergency of our institute were included in the study. All the included patients were operated using standard lateral approach and followed up to 1 year. RESULTS: Of 30 patients, 14 (48%) patients were Sander's type II, 10 (33%) were type III, and 6 (20%) were type IV. All the patients were evaluated post operatively. Articular surface of posterior facet of calcaneum and crucial angle of Gissane was maintained in all patients. Four patients had post-operative Boehler's angle <20 degrees and 26 patients had between 21 degrees and 40 degrees . All the patients having post-operative Boehler's angle <20 degrees were type IV as compared to types II and III (statistically significant). Ninety six percentage of patients having post-operative Boehler's angle 21-40 degrees were more satisfied at 1 year as compared to 25% of patients having post operative Boehler's angle <20 degrees (statistically significant). Complications were present in 6 (20%) patients. CONCLUSION: ORIF with locking compressive plate in displaced intra-articular fracture calcaneum gives good outcome. Results are more favourable in less comminuted as compared to more comminuted. Maintenance of Boehler's angle is also necessary for satisfactory results along with maintenance of articular congruence of posterior facet of calcaneum and crucial angle of Gissane. PMID- 26155050 TI - Plating for intra-articular calcaneal fractures.... Is it an overkill? AB - OBJECTIVES: Even after evolution of computerized tomography and improved surgical measures, treatment of intraarticular calcaneal fractures remains a controversy. Hence this study was carried out to compare functional outcomes of displaced intraarticular calcaneal fractures, treated with operative management with plating and conservative management with cast. MATERIAL AND METHODS: This study was carried out as a prospective, comparative study. Twenty nine (30 fractures) patients with acute, displaced intraarticular fractures of calcaneum aged 18-50 years, were enrolled in the study. Open fractures and fractures older than two weeks were excluded. 30 fractures were divided into two groups (operative and conservative; n = 15 in each). Evaluation in form of post treatment restoration of Bohler's angle, heel varus angle and with Creighton-Nebraska (C-N) score for functional outcome was done at the end of 12 months. RESULTS: When we consider the clinical evaluation under the C-N score, the results of operatively managed calcaneal fractures are slightly better than those of the conservative group. But this did not have any statistical significance. Also, there was significant difference in pre and post treatment Bohler's angle and heel varus angle in operative group. Three cases of plating suffered from post-operative wound dehiscence. CONCLUSION: A relatively better functional outcome was observed in displaced and comminuted fractures in plating, provided that the Bohler's angle was restored. In conservative group, functional outcome of minimally displaced fractures were better than displaced comminuted fractures. Post treatment Bohlers angle has prognostic importance in functional outcome. PMID- 26155051 TI - Analysis of outcome of avascular necrosis of femoral head treated by core decompression and bone grafting. AB - BACKGROUND: Femoral head is the most common bone affected by avascular necrosis. Core decompression procedure, when done in the initial stages, before collapse, may arrest or reverse the progress of avascular necrosis and thereby may preserve the normal femoral head. Hence, we have analysed the clinical, functional and radiological outcome of core decompression and bone grafting in patients with Osteonecrosis of the femoral head (ONFH) upto stage IIB (Ficat & Arlet). MATERIALS AND METHOD: A study was undertaken at our institute from June 2010 to June 2013 wherein 20 patients (28 hips) of ONFH upto grade II B (Ficat & Arlet) were treated with core decompression and the outcomes were studied. Patients were subjected to core decompression of the affected hip. All the patients were operated in lateral position. In 26/28 hips, cancellous grafting was done after harvesting graft from the posterior iliac crest. In 2 patients cortical non vascularised fibular graft was used. RESULTS: Functional outcome was assessed by Harris hip score, wherein 19 hips (67.85%) had good or excellent outcome; 1 hip (3.57%) had fair out come. However, 8 hips (28.57%) showed poor result. For stage I, 12/13 hips (92.3%) improved, whereas for Stage IIA, 6/11 hips (54.54%) showed improvement and for stage IIB, only 2/4 hips (50%) showed improvement. Less than 25% of the hips required a replacement or salvage procedure. Strict non weight bearing was complied by 23 hips (82.14%), whereas 5 hips (17.85%) were not compliant. If we exclude non compliant patients, our success rate was 92.3% for grade I, 100% for grade IIA and 50% for grade IIB. CONCLUSION: Core decompression and bone grafting provide satisfactory outcome when patients are carefully selected in early stages of the disease, before the stage of collapse. PMID- 26155052 TI - Immobilisation of extra-articular distal radius fractures (Colles type) in dorsiflexion. The functional and anatomical outcome. AB - BACKGROUND: Cast immobilisation after successful closed reduction is a standard treatment for displaced extra-articular fractures of lower end radius. The position of the wrist during immobilisation is controversial. Immobilisation in dorsiflexion prevents redisplacement after closed reduction. Our aim is to determine the effectiveness of immobilization of wrist in dorsiflexion in such cases and evaluate anatomical and functional outcome. MATERIALS AND METHODS: Study included 54 patients, above 19 years of age with closed extra-articular fractures of lower end radius treated conservatively with below elbow cast application. The wrist was maintained in 15 degrees of dorsiflexion during plaster immobilisation. At 24 weeks, functional results were evaluated with subjective symptoms and objective signs, as per modified Demerit Point Score System. Anatomical result was evaluated based on the scheme devised by Lidstrom (1959) and modified by Sarmiento et al. (1980). RESULTS: 76% patients had Excellent to Good subjective symptoms. Out of 42 patients that had residual dorsal angulation of less than 10 degrees , 37 had excellent to good functional outcome. 39 of the 43 patients who had loss of radial length less than 6 mm had excellent to good functional outcome. 40 out of 49 patients having loss of radial angulation less than 9 degrees showed excellent to good functional outcome. Functional result was directly proportional to anatomical outcome. CONCLUSION: Cast immobilization of extra articular fractures of lower end radius with wrist in dorsiflexion prevents re-displacement of the fragments resulting in satisfactory anatomical & functional outcome. PMID- 26155054 TI - Arthroscopic decompression of paralabral cyst around suprascapular notch causing suprascapular neuropathy. AB - A case of 22 year old male gymnast, who suffered from suprascapular neuropathy due to compression of suprascapular nerve by paralabral cysts around suprascapular notch, leading to marked atrophy of supraspinatus and infraspinatus muscles. After arthroscopic decompression of paralabral cysts, weakness and atrophy of the supraspinatus and infraspinatus muscles improved. PMID- 26155055 TI - Non-union of calcaneum - A rare complication of calcaneal fracture - A case report with brief review of literature. AB - Intra-articular fractures of calcaneum are known to be difficult to manage and lead to multiple complications including subtalar arthritis and malunion. However, non-union of calcaneum is rarely encountered. Only a total of six studies reporting on 12 patients could be found on reviewing the available literature (English language only). One such case of non-union of calcaneal fracture and its successful management is being reported in this case report. In addition, extremely limited literature available on calcaneal non-union is also briefly reviewed. Role of subtalar arthrodesis with internal fixation of fracture and bone grafting for successful management of this rare complication is highlighted along with the possibility of under-reporting of this relatively unknown complication. PMID- 26155056 TI - Carpal tunnel syndrome: A rare manifestation of distal radius osteoid osteoma. AB - Osteoid Osteoma is a benign bone tumor that normally affects long bones and rarely affects distal radius. Because of its nonspecific presentation in the wrist, it remains a diagnostic challenge. We report an unusual case of Osteoid Osteoma at distal radius having symptoms resembling that of carpal tunnel syndrome. The diagnosis was confirmed preoperatively with X-rays; bone scintigraphy, CT, and MRI, later histological examination confirmed the diagnoses. Surgical excision lead to a dramatic improvement in the condition of the patient. PMID- 26155053 TI - Resurgence of vitamin D: Old wine in new bottle. AB - There are early references of it in ancient text and physicians have discussed its importance and features of its deficiency in the past. Vitamin D has again regained interest with recent dramatic rise in the incidence of deficiency in the developing as well as developing world. In this review article, we discuss the biochemical and role of vitamin D in the skeletal system. We also discuss the recommended dietary requirements and features of skeletal deficiency. Extra skeletal roles of vitamin D deficiency have been a matter of debate lately and it has also been discussed in detail in this article. In conclusion, it would not be wrong to label vitamin D as one of the most important vitamin involved in the metabolism of the musculoskeletal system and any clinician, especially the orthopaedician, should be well versed with its overall mechanism and roles in the human body. PMID- 26155057 TI - Snake bite induced cellulitis leading to infected open dislocation of the first metacarpophalangeal joint - A rare complication. AB - Non-traumatic open dislocation of the first metacarpophalangeal joint is a rare phenomenon. We present a rare such occurrence secondary to snake bite induced cellulitis. A 22-year-old girl presented with pain and instability of her right thumb two months. She had snake bite two months back following which she developed cellulitis which gradually became infected. She presented with raw area over her dorsal aspect of the thumb with active infection. Radiographs revealed metacarpophalangeal joint dislocation. She underwent debridement, stabilisation and soft tissue coverage. At final follow up, she was pain free and the wound healed completely. PMID- 26155058 TI - Medial femoral condyle fracture following traumatic allogenic bone transfer - A case report. AB - Open fractures can cause an "out-in" injury, wherein a foreign body can penetrate the skin causing fracture. There are few reports of allogenic bone getting embedded in soft tissue, but one causing fracture to the host bone has not been reported till date. We present a case, wherein a large cortical bony fragment from one individual penetrated the thigh of another person causing fracture of medial femoral condyle during a head-on collision involving two motorbikes. PMID- 26155059 TI - Comment on "Plant thorn synovitis of elbow in children". PMID- 26155060 TI - Revisiting 'The Double malleoli' sign in nutritional rickets. PMID- 26155061 TI - A novel technique of patella fracture fixation facilitating early mobilization and reducing re-operation rates. AB - OBJECTIVE: Fractures of patella constitute 1% of all fractures. Various techniques have been described for internal fixation of patella fractures. Superiority of one technique over the other has long been debated. We reviewed a series of fifty-one patients with transverse or comminuted fractures of patella treated with a novel technique to assess if it had any advantages over the existing methods of fixation. DESIGN: Retrospective. SETTING: A tertiary care centre. PATIENTS & METHODS: Fifty-one patients with patella fracture OTA 34C, with a mean age of 39 years (range 18-61) were treated with technique of cerclage and two tension bands at our institute. Forty-eight patients completed the study. MAIN OUTCOME MEASUREMENTS: Range of Motion and evidence of radiological union were assessed at regular follow-ups. RESULTS: Forty-four out of forty-eight patients had gained up-to 90 degrees of active flexion at the end of 1 week. Two patients (4.2%) developed superficial infection. All fractures had united at the end of 12 weeks. Five patients (10.3%) underwent a second surgery; four (8.3%) due to implant related complications. Malunion or non-union was not noted in any of the cases. CONCLUSION: The advantages of the described method are early mobilization, elimination of k-wire related complications, and ease of use in comminuted fracture pattern as well and a lower reoperation rates as compared to the available literature. We strongly recommend its use in cases of displaced comminuted/transverse fractures of patella as an alternate method of treatment. LEVEL OF EVIDENCE: Level III. PMID- 26155062 TI - Increasing awareness of Myology: it's time for its recognition as an independent discipline within the Medical Sciences. PMID- 26155063 TI - Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages. AB - Different genetic mutations underlying distinct pathogenic mechanisms have been identified as cause of muscle fibers degeneration and strength loss in limb girdle muscular dystrophies (LGMD). As a consequence, exercise tolerance is affected in patients with LGMD, either as a direct consequence of the loss of muscle fibers or secondary to the sedentary lifestyle due to the motor impairment. It has been debated for many years whether or not muscle exercise is beneficial or harmful for patients with myopathic disorders. In fact, muscular exercise would be considered in helping to hinder the loss of muscle tissue and strength. On the other hand, muscle structural defects in LGMD can result in instability of the sarcolemma, making it more likely to induce muscle damage as a consequence of intense muscle contraction, such as that performed during eccentric training. Several reports have suggested that supervised aerobic exercise training is safe and may be considered effective in improving oxidative capacity and muscle function in patients with LGMD, such as LGMD2I, LGMD2L, LGMD2A. More or less comfortable investigation methods applied to assess muscle function and structure can be useful to detect the beneficial effects of supervised training in LGMD. However, it is important to note that the available trials assessing muscle exercise in patients with LGMD have often involved a small number of patients, with a wide clinical heterogeneity and a different experimental design. Based on these considerations, resistance training can be considered part of the rehabilitation program for patients with a limb-girdle type of muscular dystrophy, but it should be strictly supervised to assess its effects and prevent possible development of muscle damage. PMID- 26155066 TI - XII CONGRESS OF MEDITERRANEAN SOCIETY OF MYOLOGY Naples, Italy - May 18-20, 2015 Program (Summary). PMID- 26155065 TI - Letter to the Editor. PMID- 26155064 TI - Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene. AB - Becker muscular dystrophy (BMD) was first described in 1953 by Emile Becker as a benign variant of Duchenne muscular Dystrophy (DMD). Compared with DMD, BMD is clinically more heterogeneous, with initial presentation in the teenage years and loss of ambulation beyond the age of 16 and a wide spectrum of clinical presentations, ranging from only myalgias and muscle cramps to exercise intolerance and myoglobinuria, asymptomatic elevation of serum creatin-kinase, or mild limb-girdle weakness and quadriceps myopathy. About 50% of patients become symptomatic by the age of 10 and the most part by the age of 20 years. However few patients can be free of symptoms till their fifties and cases of late-onset Becker Muscular Dystrophy have also been described. In this report we describe the clinical features of patients with dystrophinopathy sharing a deletion of exons 45-55, occasionally or retrospectively diagnosed. These data are important for both the prognostic aspects of children presenting this dystrophin gene mutation, and for the genetic counseling in these families (reassuring them on the benign course of the disease), and last but not least to keep in mind a diagnosis of BMD in asymptomatic adults with mild hyperckemia. PMID- 26155067 TI - XV CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY Naples, Italy - May 20-23, 2015 - Program (Summary). PMID- 26155068 TI - Further studies on water mites from Korea, with description of two new species (Acari, Hydrachnidia). AB - New records of water mites (Acari: Hydrachnidia) from streams in South Korea are presented. Two species are described as new to science: Torrenticolaneodentifera sp. n. (Torrenticolidae) and Atractidesermilovi sp. n. (Hygrobatidae). Five species are reported as first records for Korea: Wandesia (Wandesia) reducta Tuzovskij, 1987, Wandesia (Wandesia) cf.rara Tuzovskij, 1990, Sperchon (Sperchon) orientalis Tuzovskij, 1990, Feltria (Feltria) kuluensis Tuzovskij, 1988 and Atractides (Atractides) constrictus (Sokolow, 1934). The latter species is redescribed and elevated to species rank based on new material from the Russian Far East. PMID- 26155069 TI - Discovery of the genus Formosiepyris Terayama, (Hymenoptera, Bethylidae) in Vietnam, with a description of a new species. AB - Formosiepyrisvietnamensis sp. n. (Hymenoptera: Bethylidae) is described based on material collected from Da Lat, southern Vietnam. This is the first record of Formosiepyris Terayama from Vietnam. The new species can be distinguished from other Formosiepyris species by a narrow and rounded clypeus; a mandible with three teeth; a second metasomal tergite having small, sparsely distributed punctures and smooth interspaces, except for anterior 2/5, which is microreticulate; and a head length : width aspect ratio of 10 : 11. A key to the Oriental species of Formosiepyris is provided. PMID- 26155070 TI - Four new species of Cerambycidae (Coleoptera) from Paraguay. AB - Four new species of Cerambycidae are described from Paraguay: Eraninatomentilla (Hemilophini); Mimasyngenesconcolor (Desmiphorini); Recchiadrechseli (Aerenicini); and Microibidionbimaculatum (Neoibidionini). The new species are included in known keys. PMID- 26155071 TI - A new leafminer on grapevine and Rhoicissus (Vitaceae) in South Africa within an expanded generic concept of Holocacista (Insecta, Lepidoptera, Heliozelidae). AB - A grapevine leafminer found recently in table grape orchards and vineyards in the Paarl region (Western Cape, South Africa) is described as Holocacistacapensis sp. n. It has also been found on native Rhoicissusdigitata and bred on that species in the laboratory. It is closely related to Holocacistasalutans (Meyrick, 1921), comb. n. (from Antispila), described from Durban in KwaZulu-Natal, but widespread in southern Africa and a native leafminer of various Vitaceae: Rhoicissustomentosa, Rhoicissusdigitata, Rhoicissustridentata and Cissuscornifolia. Holocacistacapensis has been found on Vitisvinifera both in Gauteng and Western Cape, the earliest record being from 1950 in Pretoria. The initial host shift from native Vitaceae to Vitis must have occurred much earlier. The species is sometimes present in high densities, but hitherto no sizeable damage to the crops has been noted. The genus Holocacista Walsingham & Durrant, 1909, previously known from the single European grapevine leafminer Holocacistarivillei (Stainton, 1855), is expanded and redescribed and for the first time reported from Africa, East and South-East Asia and Australia. It comprises seven named species and at least 15 unnamed species. The following species are also recombined with Holocacista: transferred from Antispilina: South African Holocacistavarii (Mey, 2011), comb. n., feeding on Pelargonium, transferred from Antispila: the Indian species Holocacistamicrarcha (Meyrick, 1926), comb. n. and Holocacistapariodelta (Meyrick, 1929), comb. n., both feeding on Lanneacoromandelica, and Holocacistaselastis (Meyrick, 1926), comb. n. on Psychotriadalzelii. We also remove the following from Antispila: Heliozelaanna (Fletcher, 1920), comb. n. and Heliozelaargyrozona (Meyrick, 1918), comb. n., whereas the following Indian Vitaceae feeding species are confirmed to belong in Antispila s. str.: Antispilaargostoma Meyrick, 1916 and Antispilaaristarcha Meyrick, 1916. Holocacistasalutans and Holocacistavarii are redescribed and diagnosed against Holocacistacapensis and other South African Heliozelidae. DNA barcodes are provided for 13 species of Holocacista. PMID- 26155072 TI - Captive breeding of pangolins: current status, problems and future prospects. AB - Pangolins are unique placental mammals with eight species existing in the world, which have adapted to a highly specialized diet of ants and termites, and are of significance in the control of forest termite disaster. Besides their ecological value, pangolins are extremely important economic animals with the value as medicine and food. At present, illegal hunting and habitat destruction have drastically decreased the wild population of pangolins, pushing them to the edge of extinction. Captive breeding is an important way to protect these species, but because of pangolin's specialized behaviors and high dependence on natural ecosystem, there still exist many technical barriers to successful captive breeding programs. In this paper, based on the literatures and our practical experience, we reviewed the status and existing problems in captive breeding of pangolins, including four aspects, the naturalistic habitat, dietary husbandry, reproduction and disease control. Some recommendations are presented for effective captive breeding and protection of pangolins. PMID- 26155073 TI - Taxonomic revision of the genus Prionopelta (Hymenoptera, Formicidae) in the Malagasy region. AB - In this study we revise the taxonomy of the genus Prionopelta for the Malagasy region, treating seven species, six of which are newly described (Prionopeltalaurae sp. n., Prionopeltaseychelles sp. n., Prionopeltasubtilis sp. n., Prionopeltatalos sp. n., Prionopeltavampira sp. n., Prionopeltaxerosilva sp. n.), and one redescribed (Prionopeltadescarpentriesi Santschi). One species, Prionopeltaseychelles, is restricted to Seychelles, while the six remaining species treated are endemic to Madagascar. PMID- 26155074 TI - Electron microscopy in the understanding of lacrimal drainage system. PMID- 26155075 TI - Comparison of intravitreal ranibizumab between phakic and pseudophakic neovascular age-related macular degeneration patients: Two-year results. AB - BACKGROUND AND OBJECTIVE: To compare the efficacy of intravitreal ranibizumab (IVR) for the treatment of neovascular age-related macular degeneration (nAMD) between phakic and pseudophakic eyes after a follow-up of two years. MATERIALS AND METHODS: Data were analyzed retrospectively. The newly diagnosed and treatment naive nAMD patients were included in the study. The patients were divided into two subgroups: phakic group, and pseudophakic. All patients received 3 consecutive monthly IVR injections, and then the treatment was continued on an as-needed regimen. Patients were examined monthly, and the data at the baseline, at month 6, 12, 18, and 24 were evaluated. The changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of injections were compared between the two groups. RESULTS: The study included 92 eyes of 87 patients (58 phakic, 34 pseudophakic). Mean logarithm of the minimal angle of resolution (LogMAR) VA at the baseline, and at month 6, 12, 18, and 24 was 0.89, 0.74, 0.75, 0.73, and 0.75, in the phakic group; and 0.79, 0.71, 0.66, 0.70, and 0.70 in the pseudophakic group, respectively. The change in mean BCVA from the baseline to month 6, 12, 18, and 24 was not statistically different between the two groups (p = 0.4, p = 0.9, p = 0.5, p = 0.6, respectively). Mean injection number at month 24 was 7.9 and 8.1 in the phakic and pseudophakic group, respectively (p = 0.7). CONCLUSION: Intravitreal ranibizumab treatment on an as needed treatment regimen is effective in preserving vision and improving central retinal thickness in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment, and the number of injections were similar in the phakic and pseudophakic nAMD patients after a follow-up time of 24 months. PMID- 26155076 TI - Factors affecting visual acuity after one year of follow up after repeated intravitreal ranibizumab for macular degeneration. AB - AIM: Providing intravitreal ranibizumab therapy for neovascular age related macular degeneration (nARMD) is a source of increasing strain for many UK eye departments. Whilst most units attempt to adhere to the product licence of following up patients at four weekly intervals; delays in follow up appointments can and do occur. We aim to see if mean follow up intervals during the maintenance phase are correlated with visual outcomes at one year and perform a multivariate analysis of patient factors in a bit to understand the factors affecting visual acuity outcomes. METHOD: A continuously updated prospective audit of patients receiving ranibizumab therapy at the Royal Gwent Hospital was accessed and a coefficient of determination and Spearman's rank test undertaken to see whether mean follow up delays resulted in visual acuity penalties after nine months of maintenance. Multivariate analysis using ANOVA was then undertaken to examine in more detail the various factors affecting visual acuity outcomes. RESULTS: 805 eyes of 708 patients were included in the study. Mean follow up intervals varied between 28.0 and 96.3 days over the first six treatments of the maintenance phase (mean 49.2 - SD 10.7) with a mean change in visual acuity from baseline of +7.1 letters at 12 weeks and +4.6 letters at 52 weeks. There was a negative correlation seen between visual acuity gains after nine months of the maintenance phase and increasing clinic follow up times although Spearman's rank analysis demonstrated a correlation coefficient of only -0.078, which was not statistically significant. Variability in follow up appointments resulting in worse outcomes was however significant (p < 0.01), as was increasing age at presentation (p = 0.04). Smoking was found to decrease age of presentation by six years (74.2 years vs 80.0 years). The adjusted R (2) for the whole analysis was 0.44. CONCLUSION: Wide variation in follow up intervals was associated with a worse visual acuity outcome although longer mean follow up interval was not. Smokers presented at a significantly younger age than non-smokers or ex-smokers. This was a large study with an adjusted R (2) of 0.44. The results are relevant to other macular degeneration service providers around the world. PMID- 26155077 TI - Scleral buckling surgery using multiple radial buckles: A valid option? AB - PURPOSE: To determine whether radial buckling surgery using two or more radial buckles with or without circumferential silicone tires is still a treatment option for rhegmatogenous retinal detachment (RRD) in the current scenario. METHODS: Retrospective chart review. Patients with RRD with two or more horse shoe tears with/without proliferative vitreoretinopathy up to grade C1 who underwent buckling surgery using at least two radial buckle segments without encircling bands or drainage and with at least a 3 year follow up were included in the study. Data collected included demographics, corrected distance visual acuity (CDVA) at baseline and final follow up, details of the examination, surgical procedure(s) and complications noted, if any. Appropriate statistical analysis was done. Statistical significance was set at p < 0.05. OUTCOME MEASURES: Proportion of patients who had an attached retina at final follow up, improvement in CDVA and complications. RESULTS: 25 patients (25 eyes; 12 males and 13 females; 9 pseudophakic) were included. MEDIAN AGE: 35.15 +/- 8.32 years. Median baseline CDVA: 1.97 +/- 1.12 log MAR. Median final CDVA: 0.65 +/- 0.37 log MAR (significant improvement). Most common presenting complaint was decreased vision (87.5%). Number of radial buckle segments placed varied between 2 and 4 per eye. One patient required vitrectomy for persistent retinal detachment. One required buckle removal for infection 5 years after the primary procedure. One patient required strabismus surgery. MEDIAN FOLLOW UP: 12.25 years +/- 2.14 years. None of the other patients had any complications. CONCLUSION: Radial buckling surgery (two or more segments) is a reasonably safe and valid alternative to vitrectomy for RDs with multiple breaks in different planes. PMID- 26155078 TI - Efficacy and safety of 1% forskolin eye drops in open angle glaucoma - An open label study. AB - PURPOSE: Current treatment for glaucoma includes beta-blockers and prostaglandin analogues which have their own disadvantages. Thus a need exists for new ocular hypotensive agents that are more efficacious and have fewer side effects. Therefore, forskolin eye drops 1%, through herbal product; a clinical trial was carried out for the safety and efficacy in the treatment of open angle glaucoma. METHODS: Ninety adult male/female patients of 18-60 years of age, of either sex, suffering from open angle glaucoma with an intraocular pressure (IOP) of more than 24 mm Hg were enrolled in the study. Patients were advised to instill 2 drops thrice a day (8:00 h, 14:00 h and 20:00 h) and tonometric readings were recorded on baseline visit and on Visit 2, i.e. end of 1st week, Visit 3-2nd week, Visit 4-3rd week, and Visit 5-4th week. The reduction in IOP across each time point from untreated baseline visit and reduction in IOP across various study visits were measured. RESULTS: The mean (95% CI) difference in reduction in IOP was 4.5 mm Hg (P < 0.05) in the right eye and was 5.4 mm Hg (p < 0.05) in the left eye from baseline visit (Visit 1) to final visit (Visit 5). CONCLUSIONS: Forskolin 1% eye drops can be a safe alternative to beta blockers in glaucoma patients having concomitant asthma. PMID- 26155079 TI - Can ganglion cell complex assessment on cirrus HD OCT aid in detection of early glaucoma? AB - CONTEXT: Ganglion cell complex is damaged early in glaucoma. Does this loss of GCC help in early diagnosis of glaucoma. AIMS: To compare the RNFL thickness and ganglion cell complex (GCC) in diagnosed patients of glaucoma, pre-perimetric glaucoma and normal controls. SETTINGS AND DESIGN: Case controlled, observational study. METHODS AND MATERIAL: 33 glaucoma patients, 45 pre-perimetric glaucoma, and 30 controls were enrolled in the study. ONH parameters on cirrus HD OCT like CD ratio, para papillary RNFL thickness and GCC were calculated for each case. STATISTICAL ANALYSIS USED: ANOVA test to analyse differences between groups. ROC for ganglion cell layer. RESULTS: RNFL thickness was 71.6 MU and GCC was 69.19 MU in glaucoma patients. RNFL thickness was 77.31 MU and GCC was 71 MU in pre perimetric glaucoma and 99.6 MU and 85.16 MU in controls respectively. The difference of mean for RNFL and GCC by ANOVA was statistically significant for controls, glaucoma patients and pre-perimetric glaucoma patients. RNFL (p < 0.001) and GCC (p < 0.001). Receiver operating characteristic curve for GCC was 0.83 (p < 0.000). CONCLUSIONS: The RNFL analysis is increasingly being used as newer tool in diagnosis of glaucoma. In addition, GCC can be used as a supplementary tool in picking up cases of pre-perimetric glaucoma as loss is significant in pre-perimetric glaucoma also. PMID- 26155080 TI - Management of acquired punctal stenosis with perforated punctal plugs. AB - PURPOSE: To evaluate the efficiency of perforated punctal plug in acquired punctal stenosis. MATERIALS AND METHODS: Forty-five eyes of 33 patients who had epiphora due to punctal stenosis were included in this study. After biomicroscopic examination and lacrimal dilatation punctal stenosis was managed with the perforated punctal plugs in all patients. In the following period epiphora, plug tolerance, lacrimal drainage were evaluated and graded. Lacrimal drainage was evaluated with fluorescein dye disappearing test. RESULTS: The age of the patients ranged between 31 and 80 (mean 55.78 +/- 13.11). Preoperatively punctal dilatation and lacrimal system irrigations were performed on all patients. Lacrimal system irrigation was positive in all patients. Perforated punctal plugs were placed in the inferior puncti in all patients. The plugs were explanted 6 months after operation. The follow-up period ranged between 6 and 24 months. Plug tolerance was good in 97.8% of the eyes in the 1st month visit. Epiphora decreased remarkably in 88.9% of the patients 1 month after plug implantation, except one whose plug dropped off spontaneously in 2 weeks. Fluorescein disappearing times were found under 3 min in 97.8% of the eyes after plug explanations. CONCLUSION: Punctum stenosis is one of the several disorders that cause lacrimal drainage obstruction. Perforated punctal plugs are found convenient and effective in managing punctal stenosis. PMID- 26155081 TI - Retinal vascular fractals in Behcet's Disease: A screening method? AB - OBJECTIVE: The branching pattern of retinal vessels may be affected in Behcet's Disease (BD). Fractal analysis can be used as a new method to quantify the changes of the vascular branching pattern. In this study, we examined, for the first time, the relationship between retinal fractal dimension (D f) and retinal vascular changes seen in patients with BD. METHODS: We conducted a retrospective study of 10 new cases of BD with clinically ocular involvement. Color fundus images taken from both eyes of the participants have been analyzed, and D f of the whole retinal vasculature was quantified using a novel computer-based program. The resultant D f was compared with that of healthy individuals. RESULTS: The mean D f, calculated from 20 fundus images of cases with BD, was 1.59 +/- 0.064. It was lower than that of healthy participants (1.65 +/- 0.060) significantly (P = 0.013). CONCLUSION: Retinal fractal analysis of cases with BD has been performed for the first time, and the results showed that early retinal vascular changes seen in new cases of BD are associated with lower retinal D f. Retinal fractal analysis in BD can be practically utilized as a potential tool for screening of retinal involvement, evaluating the prognosis and the response to treatment. PMID- 26155083 TI - Glaucoma after open globe injury. AB - Ocular trauma remains a core root of avoidable blindness worldwide. Corneal scarring, lens injury, glaucoma, vitreous hemorrhage, retinal or choroidal detachment and endophthalmitis are sequel to ocular trauma that can lead to blindness. Very few studies have been published to tackle the risk of developing post-traumatic glaucoma after open globe injuries (OGI), however, there are many articles discussing closed eye injury. This review article aims to cover the incidence, risk factors, causes and treatment of glaucoma after open globe injury. PMID- 26155082 TI - Boston keratoprosthesis - Clinical outcomes with wider geographic use and expanding indications - A systematic review. AB - Over 2 decades of research, several design modifications, and improvements in post-operative management have made Boston keratoprosthesis (B-KPro) a viable option for patients with corneal blindness for whom traditional keratoplasty procedure has a very low probability of success. In this systematic review, we examined the indications, visual outcomes, complications and retention rate of the literature published in the past 10 years (2005-2014). While most of the studies report smaller datasets (typically <50 eyes), some of the recent multicenter studies have reported large datasets (up to 300 eyes). Most of the literature is published from the US; however, last few years have witnessed some papers reporting the successful use of B-Kpro from developing countries or arid climatic conditions (such as the Kingdom of Saudi Arabia). Due to differences in the causes of corneal blindness in different geographic regions, newer indications for B-Kpro are emerging (e.g. trachoma). Additionally, improving clinical outcomes and increasing surgeon confidence have also expanded indications to include cases of unilateral visual impairment and paediatric age. We observed that there is growing body of evidence of successful clinical use of B-KPro; however, financial challenges, lack of trained surgeons, shortage of donor corneas must be overcome to improve accessibility of B-KPro. PMID- 26155084 TI - Ocular problem in Ebola virus infection: A short review. AB - In 2014, the outbreak of Ebola virus infection occured in Africa and became the global concern. The infection is an acute febrile illness and the patient can have several clinical manifestations including the hemorrhage. The ocular manifestation of Ebola infection is interesting. In this brief review, the authors summarize on the ocular manifestation in Ebola virus infection. PMID- 26155085 TI - Optic neuropathy secondary to dasatinib in the treatment of a chronic myeloid leukemia case. AB - The drug dasatinib is a new therapeutic option for patients with chronic myeloid leukemia (CML) as well as acute lymphocytic lymphoblastic leukemia (ALL). However, the scientific literature has not reached a consensus regarding the types of secondary ophthalmologic effects that this drug may have. In this study, we present the case of a 36-year-old male patient who was treated with dasatinib. Two and a half months later, this patient began to experience progressive visual loss in the superior visual field of both eyes. After ruling out various diagnostic options and performing extensive complementary tests, the suspected diagnosis was compatible with optic neuropathy secondary to dasatinib. The patient partially improved after stopping this medication and receiving oral corticosteroid treatment. Although secondary ophthalmological effects related to dasatinib are practically non-existent, our case is the first to report optic neuropathy secondary to this drug. PMID- 26155086 TI - Steroid-induced central serous chorioretinopathy in a patient with non-arteritic anterior ischemic optic neuropathy. AB - Non-arteritic anterior ischemic optic neuropathy is a result of an infarction of the small vessel at the anterior portion of the optic disc and causes acute, unilateral, painless visual loss. There is no generally accepted treatment method for this condition but some medical and surgical treatments are recommended. Earlier studies show that visual acuity recovery was better with corticosteroid medication compared to non-treated patients. However corticosteroids may cause side effects such as cataract, increased intraocular pressure and rarely central serous chorioretinopathy. This case report presents a patient with central serous chorioretinopathy secondary to corticosteroid medication. PMID- 26155087 TI - Bilateral Mooren's ulcer - Customised corneal graft with additional amniotic membrane graft. AB - Mooren's ulcer (MU) is a rare and painful peripheral corneal ulceration which occurs in the absence of any associated scleritis, and any detectable systemic disease. A 60-year-old male patient was referred to us with bilateral peripheral corneal ulceration. Best corrected visual acuity (BCVA) in both eyes was counting finger at one metre. The right eye showed a 180 degrees thinning with perforation at 8 o'clock position. The left eye showed a 360 degrees thinning with central contact lens type cornea. After complete blood analysis we started the patient on cyclophosphamide orally along with high doses of oral steroids. A crescentic excision of the thinned cornea and crescentic customised corneal graft with additional amniotic membrane graft (AMG) was done first for the right eye and a 360 degrees peripheral lamellar corneal graft with additional AMG for the left eye. The BCVA of RE was 1/60 improving to 6/36 with plus ten aphakic glasses and LE was 3/60. Hand fashioned full thickness crescentic customised corneal graft with additional AMG and a peripheral 360 degrees lamellar corneal graft with additional AMG in these cases are a novel approach to Mooren's ulcer with gratifying results. PMID- 26155088 TI - Frontal osteomyelitis presenting as upper eyelid ectropion: A cautionary tale. AB - Frontal osteomyelitis is a rare clinical entity that can occur as sequelae to frontal sinusitis, head trauma, as a postoperative complication following sinus surgery or due to haematogenous spread. It usually presents with a soft, fluctuant forehead swelling with pain and fever. Cicatricial ectropion is an extremely rare feature of frontal osteomyelitis. We present a young male patient presenting with cicatricial ectropion that occurred as the sole manifestation of an underlying frontal osteomyelitis. Extensive Medline search did not find any such reported case. We feel that frontal osteomyelitis should be kept in mind as a possible etiology when considering the differential diagnosis of cicatricial ectropion. PMID- 26155089 TI - A case of choroidal melanocytoma mimicking a choroidal melanoma. AB - A 17-year-old young girl was seen by us with complaints of progressive, painless decreasing vision in one eye for the last 4 years. No other supporting history could be elucidated. On examination, a large choroidal mass was found. Since the features were suggestive of malignant melanoma of the choroid, an enucleation of the eye was performed. Subsequently, histopathological examination of the enucleated eye revealed findings consistent with melanocytoma of the choroid. This case is unique in that the patient was of relatively young age and the tumor was huge compared to previous such reports. PMID- 26155090 TI - Ultrastructural differentiation of sperm tail region in Diplometopon zarudnyi (an amphisbaenian reptile). AB - Diplometopon zarudnyi, a worm lizard belongs to amphisbaenia under trogonophidae family. This species exists in limited areas of the Arabian Peninsula and is an oscillating digger found in sub-surface soils. The present study aimed to investigate the sperm tail differentiation in D. zarudnyi. Ten male adults of D. zarudnyi were collected from Riyadh during April-May 2011. To study the sperm tail at the ultrastructural level the testes were fixed in 3% glutaraldehyde, than post fixed in 1% osmium tetaroxide followed by dehydration in ethanol grades; samples were cleared in propylene oxide and embedded in resin. Tail formation begins by the moving of centrioles and mitochondria towards the posterior pole of sperm head. Simultaneously many microtubules of the midpiece axoneme were enclosed by a thick layer of granular material. Mitochondria of midpiece lie alongside the proximal centriole which forms a very short neck region and possess tubular cristae internally and concentric layers of cristae superficially. During this course a fibrous sheath surrounds the axoneme of mid and principal piece. At the end dissolution of longitudinal manchette takes place. The mitochondria then rearrange themselves around the proximal and distal centrioles to form a neck region. Later, the fibrous sheath surrounds the proximal portion of the flagella. This part along with sperm head of D. zarudnyi provides a classical model that could be used in future for evolutionary and phylogenetic purposes of class reptilia. PMID- 26155091 TI - B and T cell values in peripheral blood in Polish mixed breed rabbits. AB - Due to the lack of reference values for immunological parameters in Polish mixed breed rabbits, the study was aimed at developing standards for B-cells with CD19+ receptor, and T-cells with CD5+ receptor, and their subpopulations, namely T cells with receptors CD4+, CD8+ and CD25+ in peripheral blood of Polish mixed breed rabbits, as well as at assessing the impact of four seasons and sex of the animals on such values. The results of the study not only are the source of reference values, but also revealed that the season of the year and sex of the rabbits affect the percentage of B- and T-cells and their subpopulations in peripheral blood. PMID- 26155092 TI - Effect of oral administration of kynurenic acid on the activity of the peripheral blood leukocytes in mice. AB - Kynurenic acid (KYNA), an endogenous tryptophan metabolite, is a selective ligand of the GPR35 receptor, expressed mainly on the immune cells. In inflammatory conditions, by affecting this receptor, KYNA inhibits the synthesis of pro inflammatory cytokines and probably protects tissues from oxidative damage. However, we lack data regarding the effect of exogenous KYNA on the activity of immune cells in healthy individuals. The objective of this study has been to determine the influence of kynurenic acid administered to mice in different doses (2.5, 25 or 250 mg/l) and for different time periods (3, 7, 14, 28 days) in drinking water, on the activity of their peripheral blood leukocytes. The determinations comprised the proliferative activity of lymphocytes (MTT assay) and the phagocytic activity as well as the respiratory burst activity of granulocytes and monocytes (Phagotest, Phagoburst). It was only the lowest KYNA dose that influenced the mitogenic response of lymphocytes, namely by increasing the proliferation of T cells. The impact on the phagocytic activity was varied with KYNA dose and administration time. However, all the KYNA doses significantly lowered the activity of oxidative burst in phagocytes, which was probably associated with its antioxidant properties. In the light of the research results, kynurenic acid may find applications as an immuno-modulating agent able to correct an excessive or insufficient response of phagocytizing cells, protecting an organism from oxidative stress. PMID- 26155093 TI - Feeding mice with Aloe vera gel diminishes L-1 sarcoma-induced early neovascular response and tumor growth. AB - Aloe vera (Aloe arborescens, aloe barbadensis) is a medicinal plant belonging to the Liliaceae family. Aloe vera gel prepared from the inner part of Aloe leaves is increasingly consumed as a beverage dietary supplement. Some data suggest its tumor growth modulatory properties. The aim of the present study was to evaluate in Balb/c mice the in vivo influence of orally administered Aloe vera drinking gel on the syngeneic L-1 sarcoma tumor growth and its vascularization: early cutaneous neovascular response, tumor-induced angiogenesis (TIA test read after 3 days), and tumor hemoglobin content measured 14 days after L-1 sarcoma cell grafting. Feeding mice for 3 days after tumor cell grafting with 150 MUl daily dose of Aloe vera gel significantly diminished the number of newly-formed blood vessels in comparison to the controls. The difference between the groups of control and Aloe-fed mice (150 MUl daily dose for 14 days) with respect to the 14 days' tumor volume was on the border of statistical significance. No difference was observed in tumor hemoglobin content. PMID- 26155094 TI - Dynamic changes of DC and T cell subsets in mice during Echinococcus multilocularis infection. AB - The aim of this study was to determine the dynamic changes of dendritic cell (DC) pheno-types and T cell in response to Echinococcus multilocularis (Em) infection in BALB/c mice. Mice comprised the control and Em-infected group. At day 0, 2, 7, 30, 60, 90 and 120 after infection, the size of larval cysts, the phenotype of DC and Th in splenocytes and the expression of CD40, CD86, TLR2 and TLR4, on DCs sulfur were examined. The results show that after 60 days' infection, larval cysts grow on the surface of liver, and they become larger over time. Compared with the control mice, MHC I and MHC II expressions on DC were significantly increased at day 7 (p < 0.05). At the same time, CD40, CD86, TLR2 and TLR4 increased rapidly, but after that they decreased gradually. At day 120, those markers were lower than in the control group. The ratio of CD4/CD8 was normal during 90 days of infection, while at day 120, a decline in CD4 T cell and increase in CD8 were foundleading to the inversion of the CD4/CD8 ratio. Our findings suggest that within the 120 days of Em infection, the major function of DC is to present antigens. Immune response is provided predominantly by Th1 cells, inducing host immune response against Em. However, after 120 days, DC matured and the function was suppressed. Furthermore, inversion of the CD4/CD8 ratio is beneficial to the growth of Em, thus favoring its immune evasion. PMID- 26155095 TI - Molecular cloning and sequencing analysis of the interferon beta from Coturnix. AB - One pair of primers was designed according to Gallus and Meleagris gallopavo interferon beta (IFN-beta) sequences published in GenBank. The primers and RNA extraction from the spleen of Coturnix were used to amplify Coturnix IFN-beta cDNA by real-time polymerase chain reaction (RT-PCR). The product was cloned into pEasy-T1 vector. Evaluating recombinant plasmid by PCR and restriction enzyme digestion. Sequence the cloning sequences, comparing the sequencing results by NCBI. We successfully got a Coturnix IFN-beta partial sequence. The sequence was subtyped and put to homologous analysis. The results suggested the homology of IFN-beta gene of Coturnix and gene of Coturnix and chicken (88.7%), the homology of IFN-beta gene of Coturnix and chicken (88.7%), the homology of IFN-beta gene of Coturnix and Anas platyrhynchos (72.5%), the homology of IFN-beta sequence registered in GenBank. The analysis of the genetic tree showed that the relationship of Coturnix and chicken IFN-beta had a high homology. It can be seen that in this study we successfully got a partial sequence of IFN-beta of quail. PMID- 26155096 TI - Immunomodulatory efficiency of Etroplus suratensis muscle protein. AB - The protein extract of Etroplus suratensis (E. suratensis) collected from Bavanisagar dam was found to be effective against all tested organisms with an inhibition zone ranging from 0.2 to 1.9 mm. When the result was compared with standard antibiotic Streptomycin, a moderate efficiency was observed. In vitro, an antibacterial assay was used to assess the efficacy of fish protein in inhibiting the growth of pathogenic microbes. The fish protein of E. suratensis collected from Bavanisagar had a broad spectrum of antibacterial potential. The minimal inhibitory concentrations of E. suratensis against pathogens are the highest in protein collected from Bavanisagar. In the fish protein collected from Bavanisagar, it has been shown that the minimum bactericidal concentration (MBC) value is higher in Bacillus subtilis (0.85/20 ug/ml) and the lowest in Micrococcus (0.1/100 ug/ml). The sub-lethal dose of fish protein was estimated at 1/10 of 96 h LD50 dose (30 ug/ml/Kg), the antibody response was significantly enhanced on day 14 and day 21 (p < 0.01). The highest IgG level was noticed on day 21, which decreased towards day 28. This result showed the antibody production with an increased IgG concentration. The above results demonstrate that fish protein extracts have great potential as immunostimulants against the microorganisms and they can be used in the treatment of infectious diseases caused by the microorganisms. PMID- 26155097 TI - Genetic and antigenic analysis of mink's immunoglobulin G Fc region. AB - Mink's immunoglobulin (Ig) G Fc gene was cloned, the gene was analyzed by phylogenetic analysis, and western blot was done to prove that the detection of distemper and canine parvovirus in dogs and minks can be universal. In order to get the certain length of Fc segment gene, a pair of primers is designed, which according to the Fc segment gene sequences of mink's IgG (L07789) published by GenBank, extracted total RNA from the spleen of minks and amplified it by RT-PCR. The results showed that the Fc segment gene contained 606 bp. Then it was sequenced after the amplified fragments were cloned into the vector PEasy-T1. Then the genetic evolution was analyzed. An antibody hybridization test was done through western blot. The results showed that nucleotide sequence homologies between minks and canines were 85%, and amino acid sequence homologies between minks and canines were 80.5%. Mink IgG heavy chain can effectively combine to anti-dog IgG by western blot. It was concluded that mink's and dog's IgG Fc had the closest relationship in mammalian through the analysis of the genetic evolution. Based on the above analysis and related literature, we concluded that we could detect mink diseases with a dog diagnosis reagent, or treat mink diseases with dog antiserum. PMID- 26155098 TI - Effects of microRNA-21 on the interleukin 12/signal transducer and activator of transcription 4 signaling pathway in asthmatic mice. AB - OBJECTIVE: To study the effect of microRNA-21 (miRNA-21) on the regulation of the interleukin 12 (IL-12)/signal transducer and activator of transcription 4 (STAT4) pathway in the lung tissue of asthmatic mice. MATERIAL AND METHODS: Forty five male C57BL/6 mice were randomly divided into three groups of 15 mice each: normal control, asthmatic model, and dexamethasone. Our mouse model of allergic asathma was established using OVA sensitization and challenge. Hematoxylin and eosin staining was performed to observe the pathological changes in lung tissue morphology. Both the total cell number and the amount of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) were manually counted. The expression of miRNA-21 was detected by real time quantitative PCR. The expression levels of IL 12 and STAT4 in lung tissue were assayed via western blot, and immunohistochemistry was used to observe the distribution of their expression. RESULTS: The expression levels of miRNA-21 as well as the total number of BALF cells and EOS were significantly higher in the asthmatic model group than in the control or dexamethasone groups, with significantly higher amounts found in the dexamethasone group than in the control group. The expression levels of IL-12 and STAT4 proteins were lower in the asthmatic model group than in the control and dexamethasone groups, with a significantly lower expression of IL-12 and STAT4 in the dexamethasone group than in the control group. CONCLUSIONS: The expression level of miRNA-21 was significantly increased and the expression level of IL-12 and STAT4 proteins was significantly decreased in allergic asthmatic mice compared with normal control mice. These findings suggest a role for miRNA-21 and the IL-12/STAT4 pathway in the development of allergic asthma. PMID- 26155099 TI - Purification of pituitary autoantigen by column liquid chromatography and chromatofocusing. AB - INTRODUCTION: Pituitary autoantibodies can be determined both in patients with pituitary disease as well as patients with autoimmune endocrine diseases. The purpose of the study was to isolate and purify pituitary autoantigen using sera of patients and the microsomal fraction of the pituitary. MATERIAL AND METHODS: To isolate a pituitary autoantigen, patient sera were used, which showed a strong immune response to pituitary antigens. Pituitary microsomal fractions were prepared from pituitary tissue homogenates. In the study, sera of patients with pituitary disease, Addison and Graves' disease were used. The initial stages were carried out by affinity chromatography on CN -Br sepharose column whereas purification was continued by column liquid chromatography on AcA54 Ultrogel. Chromatofocusing was performed by Polybuffer exchanger PBE 94. RESULTS: (125)I labeled pituitary antigens after isolation appeared in column chromatography in three peaks. The first peak contained 50-70 kDa proteins, the second peak - 17 to 22 kDa proteins and the third peak contains (125)-iodides. Three fractions obtained from filtration on Ultrogel were separated in a polyacrylamide gel. In the first peak two bands 67 and 55 kDa appeared. The second peak contained low molecular weight substances, and the third peak contained (125)I. The first peak from Ultrogel was isolated by chromatofocusing - the first peak with pH 5.9 and the second one with pH 4.9. CONCLUSIONS: Isolation and purification of pituitary autoantigen with the use of column liquid chromatography and chromatofocusing resulted in obtainment of two antigenic proteins of specific gravity of 67 and 55 kDa. PMID- 26155101 TI - Primary systemic amyloidosis as a real diagnostic challenge - case study. AB - Primary amyloidosis (AL) is a rare variety of plasma cell dyscrasia, the diagnosis of which is often difficult to establish. Pathogenesis of amyloidosis involves extracellular deposition of insoluble protein fibrils in tissues, leading to insufficiency of affected organs. According to various sources, mean survival rate of patients with primary amyloidosis ranges from 12 to 24 months, making primary amyloidosis a disease with a very poor prognosis. Survival rate is significantly lowered in case of cardiac manifestation of amyloidosis (about 6 months survival in untreated patients). In recent years a considerable progress in AL treatment has been observed. Nowadays we are able not only to delay progression of amyloidosis, but also to improve the function of the affected organs. Unfortunately as first signs and symptoms of AL are usually nonspecific, the diagnosis of AL is often delayed, resulting in late introduction of optimal therapy. There are many diagnostic tests which can be used in diagnostic process of amyloidosis, i.e. electrophoresis, serum and urine immunofixation or affected organs and bone marrow biopsy. On establishing the diagnosis in a patient with suspected amyloidosis it should be remembered that particular diagnostic methods vary considerably in sensitivity. The aim of this paper is to present a case report of a 27-year-old patient with primary amyloidosis focusing on diagnostic aspect of this condition. On the basis of this case, the authors would like to emphasize the value of precise diagnostic process, with immunological techniques playing undoubtedly a crucial role. PMID- 26155100 TI - Reactivity of the immunological system of rats stimulated with Biolex-Beta HP after cyclophosphamide immunosuppression. AB - The objective of this study was to determine the stimulating effect of the Biolex Beta HP (beta-1,3/1,6-D-glucan) dietary supplement on selected parameters of specific and non-specific humoral and cellular immunity in rats immunosuppressed with cyclophosphamide. The experimental material comprised 40 Wistar rats, divided into two equal groups: control and experimental. In the course of 3 successive days, the rats from the experimental group were administered cyclophosphamide intramuscularly at a rate of 50 mg/kg BW per day. On the 8(th) day of the experiment, 10 control and 10 experimental rats were sacrificed, and total protein and gamma-globulin levels, lysozyme and ceruloplasmin activity were determined in the blood serum. The proliferative response of blood lymphocytes after stimulation with lipopolysaccharide or concanavalin A, respiratory burst activity and the potential killing activity of phagocytes were determined in whole heparinised blood. Starting on the 8(th) day of the experiment, the feed of the remaining rats from the experimental and control groups was supplemented for 14 consecutive days with Biolex-Beta HP at a rate of 50 mg/kg BW per day. On day 22, arterial blood samples were collected and immune parameters were determined. The results indicate that beta-1,3/1,6-D-glucan has a positive effect on the analysed parameters of non-specific cellular and humoral immunity after cyclophosphamide-induced suppression. Nevertheless, the observed effect only marked a return to the norm, as most of the analysed parameters were merely restored to their initial levels, with the exception of lysozyme activity, which considerably exceeded the level noted before immunosuppression. PMID- 26155102 TI - Evaluation of complement regulatory components in patients with atypical hemolytic uremic syndrome. AB - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS), a rare disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure, is associated with mutations and polymorphisms in various components and regulators of the complement alternative pathway (AP), including factor H, factor I, membrane cofactor protein (MCP or CD46) and factor B. This impaired regulation of the alternative pathway leads to a procoagulant state with microthrombi formation in the renal vasculature, which influences disease onset and progression. AIM OF THE STUDY: To evaluate the role of complement regulatory factors in occurrence of aHUS; we also included evaluation of ADAMTS13 activity and autoantibody against ADAMTS13 in order to exclude thrombotic thrombocytopenic purpura (TTP) cases, which might have overlapping clinical and laboratory findings. MATERIAL AND METHODS: This study was conducted on 273 individuals with aHUS. Diagnosis was based on clinical manifestations, kidney function tests, red blood cell count, morphology and reticulocyte count. Then, the ADAMTS 13 autoantibody and activity and also complement factor B, complement factor H (CFH) and complement factor-I (CIF) were analyzed. Finally, the statistical analysis was performed by SPSS software. RESULTS: The mean age of our patients was 27.3 years, 55% were female and 45% were male. The mean levels of urea and creatinine concentration were 92.9 mg/dl and 5.1 mg/dl, respectively. The mean levels of RBC count, Hb and HCT in these patients were lower than normal but the mean percentage of reticulocyte count was higher than normal (2.5%). The assessment of complement regulatory factors revealed that the B and H factors levels were normal except in two cases but the level of factor I was higher than normal. CONCLUSIONS: According to the results of this study, it seems that up regulation of factor I had a significant role in occurrence of aHUS in our study group. PMID- 26155103 TI - Imbalance of Th17 and T-regulatory cells in peripheral blood and synovial fluid in treatment naive children with juvenile idiopathic arthritis. AB - OBJECTIVES: The imbalance between Th17 and T regulatory cells (Tregs) may be a key event in development of autoimmunity. The problem is poorly explored in juvenile idiopathic arthritis (JIA) so far. In this study, peripheral blood (PB) and synovial fluid (SF) Tregs and Th17 cells from were assessed in untreated JIA children. MATERIAL AND METHODS: In 50 children with JIA the PB or SF percentages of Tregs and Th17 cells were assessed by flow cytometry, in comparison with PB Tregs and Th17 cells from 28 healthy controls. Additionally, in both groups the levels of proinfammatory cytokines, such as interleukin (IL)-1beta, IL -6, IL 17, IL -21, IL -23 and tumor necrosis factor alpha (TN F-alpha) were assessed using ELI SA method. RESULTS: The proportion of JIA PB Th17 cells was significantly higher than in the controls (p = 0.01). Serum levels of IL -1beta, IL -6, IL -17, IL -23 were also significantly higher in JIA (p = 0.011, p = 0.007, p = 0.008 and p = 0.023, respectively). The highest serum IL -6 levels were observed in oligoarthritis JIA (p = 0.031). Synovial fluid IL -21 concentration was distinctly higher in polyarticular JIA. Synovial fluid levels of TN F-alpha, IL -1beta and IL -6 were significantly higher than in JIA PB (p = 0.038, p = 0.013 and p < 0.001, respectively). There was a significant correlation between IL -6 and PB Tregs (p = 0.02). CONCLUSIONS: The results of this comprehensive analysis indicate a role of Th17 cell activation in the pathogenesis of JIA. PMID- 26155104 TI - Multiple gene mutations in patients with type 2 autoimmune pancreatitis and its clinical features. AB - BACKGROUND: It is now clear that there are two histological types (type 1 and type 2) of autoimmune pancreatitis (AI P). The histological substance of type 1 AI P is known as lymphoplasmacytic sclerosing pancreatitis (LPSP) or traditional AIP, and type 2 AIP is characterized by distinct histology called idiopathic duct centric pancreatitis (IDCP). Serum IgG4 increase is considered as a marker for type 1 AI P. Far less is known about type 2 and it lacks predicting markers, so it easily leads to missed diagnosis and misdiagnosis. THE AIM OF THIS STUDY: The aim of this study was to describe multi-gene mutations in patients with type 2 AI P and its clinical features. MATERIAL AND METHODS: Three unrelated patients with type 2 AI P, 10 cases with type 1 AIP, 15 cases with other chronic pancreatitis and 120 healthy individuals were studied. The mutations and polymorphisms of 6 genes involved in chronic pancreatitis or pancreatic cancer - PRSS1, SPINK1, CFTR, MEN1, PKHD1, and mitochondrial DNA - were sequenced. Information of clinical data was collected by personal interview using a structured questionnaire. RESULTS: Novel mutations were found in the genes encoding for MEN1 (p.546 Ala > The) and PKHD1 (c. 233586 A > G and c. 316713 C > T) from patients with type 2 AIP. What is more, the serum TCR (T cell receptor) level is relatively higher in patients with type 2 AIP than in patients with type 1 AIP and other chronic pancreatitis or normal controls. Weight loss was the major manifestation and no patients had extrapancreatic involvement in type 2 AIP. CONCLUSIONS: Type 2 AIP may occur with multi-gene mutations. For screening purposes, it is more reasonable to evaluate TCR levels in serum. PMID- 26155105 TI - Predictors of coronary collaterals in patients with non ST-elevated acute coronary syndrome: the paradox of the leukocytes. AB - AIM OF THE STUDY: Atherosclerosis represents active inflammation in which leukocytes play significant role. Coronary collateral development is a response to myocardial ischaemia. In this study we aimed to investigate the association of the leukocytes with coronary collateral development in patients with non ST elevated acute coronary syndromes (NST-ACS). MATERIAL AND METHODS: A total of 251 consecutive patients were hospitalized in our hospital with a diagnosis of NST ACS. The blood samples were collected 1-hour after admission to the hospital and peripheral leukocytes (neutrophils, monocytes and lymphocytes) were examined. All patients underwent coronary angiography. The coronary collateral vessels (CCV) are graded according to the Rentrop scoring system. RESULTS: Group 1 consisted of 146 patients with Rentrop 0 and Group 2 consisted of 105 patients with Rentrop 1, 2 and 3. The presence of CCV was significantly associated with neutrophil count, lymphocyte count, monocyte count and neutrophil-lymphocyte ratio (NLR). In subgroup analyses, higher NLR was significantly associated with good CCV development in patients with NST-ACS. CONCLUSIONS: Higher neutrophil count, monocyte count and NLR and lower lymphocyte count on admission, were associated with the presence of CCV in patients with NST-ACS. High NLR may predict good collateral development in patients with NST-ACS. PMID- 26155106 TI - The prevalence of IgG and IgA against adenoviruses in serum of children aged 11 26 months, hospitalised in the Clinical Paediatric Hospital in Warsaw, Poland. AB - Adenoviruses are widely spread viruses causing infections related mainly to children. Contact with the pathogen may result in the presence of either immunoglobulin (Ig) A or IgG antibodies in the serum. The aim of this study was to assess the prevalence of IgA and IgG antibodies against adenoviruses in serum of children aged 11-27 months, hospitalised at the Public Children's Clinical Hospital in Warsaw. Immunoassay tests DRG Adenovirus IgA ELISA and IgG DRG Adenovirus ELISA detecting antibodies against all pathogenic serotypes of adenoviruses were performed in 128 sera samples. A low percentage of positive results for both immunoglobulins, 17 cases (13.28%) for IgA and 16 cases (12.50%) for IgG antibodies respectively were reported. We conclude, that the prevalence of antibodies against adenoviruses does not coincide with epidemiological data on the spread of infections among young children. The assays performed may be more useful in distinguishing the active form of the infection from seropositivity due to prior infection. PMID- 26155107 TI - Serial ImmuKnow assay in stable kidney transplant recipients. AB - OBJECTIVES: The ImmuKnow assay (cylex Inc., Columbia, MD) has been reported to measure the global immune monitoring tool for organ transplantation recipients. We assess immuKnow ATP values in stable kidney transplant patients. MATERIAL AND METHODS: Patients who were kidney transplanted between September 2008 and May 2011 were enrolled in the prospective serial ImmuKnow assay study. The criteria of inclusion were living donor kidney transplantation (KT), no evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and PRA less than 50%. ImmuKnow assay monitoring was performed at one day before operation, post operative weeks 4, 8, 12, 16, 20, 24, 36 and 52. We excluded patients who had undergone infectious syndrome or rejection episodes during the follow-up period. RESULTS: Among 71 patients who were enrolled in prospective serial ImmuKnow assay monitoring, 37 patients were proven to stable KT patients during the follow-up period. Two hundred and twenty-four samples from 37 patients were collected. ImmuKnow value and immunosuppression drug level were compared in post operative weeks 4, 8, 12, 16, 20, 24, 36 and 52. The value of ImmuKnow assay was significantly different depending on the length of time after transplant (p = 0.038). Interestingly, the pre-transplant ImmuKnow values were lower than those of the immediate post-transplant period. CONCLUSIONS: The ImmuKnow value of stable KT recipients is different according to "time after transplant". Therefore, "time after transplant" should be considered when applying an ImmuKnow assay in clinical practice. PMID- 26155108 TI - CD4(+)CD25(+) regulatory T cells as a therapeutic target in rheumatoid arthritis. AB - CD4(+)CD25(+) T cells are regulatory T cells (CD4(+)CD25(+) Tregs), which can strengthen immune tolerance. They play a critical role in controlling the development of autoimmune diseases in animals and humans. Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the peripheral joints and eventually leads to joint destruction. Although the pathogenesis of RA remains unknown, it is supposed to be affected by autoreactive T cells and antibodies. At the same time, to make the CD4(+)CD25(+) T cells active and to increase the number of the cells are responsible in the therapy of RA in recent studies. Now, many techniques about expansion of Tregs in vitro have been established to overcome the problem of their limited numbers in vivo. It is important to carry out a study of induction or amplification of Tregs in vitro. Here, we review our current understanding of CD4(+)CD25(+) T cells in RA and the targeting of these cells in RA therapy. PMID- 26155109 TI - Probiotic lactic acid bacteria and their potential in the prevention and treatment of allergic diseases. AB - Allergy is one of the most important and very common health problems worldwide. To reduce the proportion of people suffering from allergy, alternative methods of prevention and treatment are sought. The aim of this paper is to present the possibilities of probiotics in the prevention and treatment of allergic diseases. Probiotics are live microorganisms belonging mainly to the lactic acid bacteria. They modify the microflora of the human digestive system, especially the intestinal microflora. Prophylactic administration of probiotics in the early stages of life (naturally in breast milk or milk substitute synthetic compounds) is very important because intestinal microflora plays a huge role in the development of the immune system. Prevention of allergies as early as in the prenatal and postnatal periods provides huge opportunities for inhibiting the growing problem of allergy in emerging and highly developed societies. Effects of probiotic therapy depend on many factors such as the species of the microorganism used, the dose size and characteristics of the bacteria such as viability and capacity of adhesion to the intestinal walls. Authors of several studies showed beneficial effects of probiotics in the perinatal period, infancy, and also in adults in the prevention of atopic dermatitis or allergic rhinitis. Probiotics, due to their immunomodulatory properties and safety of use are a good, natural alternative for the prevention and treatment of many diseases including allergies. It is therefore important to explore the knowledge about their use and to carry out further clinical trials. PMID- 26155110 TI - Perforin: an important player in immune response. AB - Perforin is a glycoprotein responsible for pore formation in cell membranes of target cells. Perforin is able to polymerize and form a channel in target cell membrane. Many research groups focus on the role of perforin in various diseases, immune response to bacterial and viral infections, immune surveillance and immunopathology. In addition, perforin is involved in the pathogenesis of autoimmune diseases and allogeneic transplant rejection. Natural killer (NK) cells and CD8-positive T-cells are the main source of perforin. However, CD4 positive T-cells are also able to express a low amount of perforin, when classic cytotoxicity is ineffective or disturbed. Polymerized perforin molecules form channels enabling free, non-selective, passive transport of ions, water, small molecule substances and enzymes. In consequence, the channels disrupt protective barrier of cell membrane and destroy integrity of the target cell. This review will focus on mechanisms of action and structure of perforin. Also, in this review we discuss the problem of abnormal perforin production in diseases such as: hemophagocytic lymphohistiocytosis (HLH), leukemias and lymphomas, infectious diseases and autoimmune diseases. Better understanding of the role of these molecules in health and disease will open a new field of research with possible therapeutic implications. PMID- 26155111 TI - Neutrophil extracellular traps in physiology and pathology. AB - Neutrophil extracellular traps (NETs) are developed by nature to protect the body from furious invaders. On the other hand NET s can play an important role in human pathology. Recent studies have shown that neutrophils are able to perform beneficial suicide to create an unique microbicidal net composed from cellular content attached to chromatic frame. It is a powerful tool that primary serve as protector from severe infections, but this weapon is also a double ended sword of the immunity. If overproduced NET s provoke certain autoimmune diseases, coagulation disorders and even cancer metastases. Moreover, due to the competition between host and pathogens, the microorganism have developed a width repertoire of sophisticated evading mechanisms, like creation of polysaccharide capsule or changes in cell wall charge. Therefore it is important to increase the knowledge about paths underlying NET s formation and degradation processes if we want to efficiently fight with bacterial infections and certain diseases. PMID- 26155112 TI - Effect of routine Hepatitis B vaccination program in Southeast of Turkey? Comparing of the results of HBV DNA in terms of age groups for the years 2002 and 2012. AB - Diyarbakir is the largest residential area in the Southeastern Anatolia of Turkey. Routine HBV vaccination has begun to be implemented by the Ministry of Health in Turkey in 1998. The purposes of this study were to detect the levels of HBV DNA in patients with HBV in 2012, and to compare the results of the year 2002 according to age groups. HBV DNA results of patients were divided in to seven age groups (0-14, 15-20, 21-30, 31-40, 41-50, 51-60, and > 61 years) and for comparison of HBV DNA levels of 2002 and 2012, HBV DNA values in pg/ml of year 2002 were translated into IU/ml and HBV DNA levels were grouped as < 5 pg/ml < 2.43 * 10(5) IU/ml, 5-100 pg/ml 2.43 * 10(5)-4.86 * 106 IU/ ml, 101-2000 pg/ml 4.87 * 10(6)-9.72 * 10(7) IU/ml, > 2000 pg/ml > 9.72 * 10(7) IU/ml 2-3. A statistically significant decrease was seen in the number of individuals in 0-14 age group in 2012 compared with 2002. In 2002 the rate of individuals in 0-14 age group was 18.8% whereas 4.8% in 2012. Our study was suggested that that routine HBV vaccination program, contributed to the reduced risk of HBV infection in our region. PMID- 26155113 TI - Oral administration of Aloe vera gel, anti-microbial and anti-inflammatory herbal remedy, stimulates cell-mediated immunity and antibody production in a mouse model. AB - INTRODUCTION: Aloe vera (L.) Burm. f. (Aloe barbadensis Mill) Liliaceae, succulent plant native to northern Africa, is presently cultivated in many regions of the world. Traditionally, its inner part of parenchyma, which contains aloe gel, was used for the treatment of minor wounds, inflammatory skin disorders, thermal and radiation burns and to alleviate chronic osteoarthritis pain. It also possesses some antimicrobial activity. Now, aloe gel is also increasingly consumed as a dietary supplement. Some data suggest its immunomodulatory properties. THE AIM OF THE STUDY: The aim of the study was to evaluate the influence of orally administered aloe gel on some parameters of cellular and humoral immunity viz. mitogen-induced proliferation of splenic lymphocytes and their chemokinetic activity, and anti-sheep red blood cells (SRBC) antibody production in Balb/c mice. RESULTS: Daily treatment of mice for 14 and 21 days with 50 ul or 150 ul of aloe gel dose resulted in enhanced chemokinetic activity and stronger response of their splenic lymphocytes to mitogen PHA and enhancement of anti-SRBC antibody production. PMID- 26155114 TI - The effect of interleukin 17 and Toll-like receptor 2 on CD11b expression and apoptosis of neutrophils in zymosaninduced arthritis and paw oedema. AB - We investigated the effect of interleukin (IL)-17 on Ly6G(+) cell apoptosis in zymosan-induced arthritis (ZIA) and oedema (ZIO). Zymosan injection at the ankle joint caused swelling and coincided with histological joint alterations and IL 17A expression in areas with cell infiltrates. Flow cytometry of blood demonstrated increased frequencies of Ly6G(+)CD11b(+) cells and their decreased apoptosis in ZIA. Annexin V(+) neutrophils had lower CD11b expression, unlike Annexin V(-) cells. Cell survival for 12 hours was affected neither by IL-17 nor by zymosan alone, while both stimuli diminished Annexin V(+) cell frequencies and up-regulated CD11b on Annexin V(-) cells. Interleukin 17 antagonised to the effects of zymosan in 24-hour cultures. The administration of IL-17 in ZIO increased paw thickness, enlarged the blood Ly6G(+) pool, elevated CD11b expression and decreased apoptosis. We suggest that altered neutrophil apoptosis in arthritis can be overcome by anti-IL-17 therapy combined with an inhibition of Toll-like receptor (TLR) 2 and CD11b signalling. PMID- 26155115 TI - Umbilical cord blood-derived dendritic cells loaded with BGC823 tumor antigens and DC-derived exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumor immunity in vitro and in vivo. AB - BACKGROUND: Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells and from which a significant number of dendritic cells (DCs) can be produced. But the therapeutic role of DCs and exosomes (EXO) generated from DCs is not fully elucidated. MATERIAL AND METHODS: The UCB-derived DCs were loaded with tumor antigens generated from BGC823 cell line. Exosomes were derived from these DCs by ultracentrifugation. Dendritic cells and DCex were evaluated by light microscope, transmission electron microscope (TEM), flow cytometry, and western blot assay. The therapeutic role of DCs and EXO generated from DCs were then detected in vitro and in vivo. RESULTS: Dendritic cells isolated from umbilical cord blood after loading with tumor antigens generated from BGC823 cell line could express high levels of protein molecules: MHC-I, MHC-II, CD34, CD40, CD80, CD86, CD11c and CD54 and mediate a stronger promotion of T cells proliferation. And, they could also enhance the cytotoxicity effects of the generated CTL in vitro and in vivo. Exosomes isolated from these DCs were 40-90 nm round particles with a complete membrane structure and could also expressed molecules similar to DCs. Exosomes could stimulate T cell proliferation, produce effective cytotoxicity and induce more efficient in vivo antitumor immunity. CONCLUSIONS: These results suggested that tumor antigens loaded DCs derived from unrelated umbilical cord blood or DCex can induce tumor specific cytotoxicity and this may represent a novel immunotherapy for tumors. Because of their advantage of stable, easy to store, DCex have a more brilliant prospects in the tumor immunity. ADDITIONAL INFORMATION: We reported that exosomes derived from umbilical cord blood dendritic cell (UBDC), similar to DCs, can trigger activation of T cells significantly. These data demonstrate that DC-derived exosomes (DCex) can mediate essential adaptive immune functions. PMID- 26155116 TI - Modulating effects of leflunomide on the balance of Th17/Treg cells in collageninduced arthritis DBA/1 mice. AB - To evaluated the effect and mechanism of leflunomide (LEF) in murine model of collage-induced arthritis (CIA) on modulating the balance of Th17/Treg cells. DBA mice were divided into: control, CIA, CIA + LEF and CIA + Ibuprofen group. After 14 days immunization with bovine type II collagen (CII), except control group, mice were orally administered saline (CIA group), LEF or ibuprofen daily for 14 days. The severity of arthritis joint was assessed by using arthritis score. The numbers of CD3 + CD4 + interleukin 17 (IL-17) + Th17 cells and CD4 + CD25 + Foxp3+ Tregs were determined by flow cytometry, the expression of ROR-gammat, Foxp3 and IL-21 mRNA in spleen were quantified by RT-PCR and IL-17, IL-21 and transforming growth factor beta (TGF-beta) level in serum was measured by ELISA. In comparison with CIA group, CIA + LEF and CIA + Ibuprofen group reduced the disease severity obviously (p < 0.05). Leflunomide reduced Th17 cells, the expression of ROR-gammat and IL-21 mRNA (p < 0.05) and the levels of IL-17 and IL 21 in serum. In addition, Ibuprofen but not LEF has effect on Treg cells number, Foxp3 mRNA expression and TGF-beta secretion. These results indicate that LEF effect on the balance od Th17/Treg through suppressing Th17 cells, but not stimulating Treg cells. Leflunomide may act as a potential immunomodulator for the treatment of rheumatoid arthritis (RA). PMID- 26155117 TI - Molecular cloning and sequencing analysis of the interferon receptor (IFNAR-1) from Columba livia. AB - OBJECTIVE: Partial sequence cloning of interferon receptor (IFNAR-1) of Columba livia. MATERIAL AND METHODS: In order to obtain a certain length (630 bp) of gene, a pair of primers was designed according to the conserved nucleotide sequence of Gallus (EU477527.1) and Taeniopygia guttata (XM_002189232.1) IFNAR-1 gene fragment that was published by GenBank. Special primers were designed by the Race method to amplify the 3'terminal cDNA. RESULTS: The Columba livia IFNAR-1 displayed 88.5%, 80.5% and 73.8% nucleotide identity to Falco peregrinus, Gallus and Taeniopygia guttata, respectively. Phylogenetic analysis of the IFNAR1 gene showed that the relationship of Columba livia, Falco peregrinus and chicken had high homology. CONCLUSIONS: We successfully obtained a Columba livia IFNAR-1 gene partial sequence. Analysis of the genetic tree showed that the relationship of Columba livia and Falco peregrinus IFNAR-1 had high homology. This result can be used as reference for further research and practical application. PMID- 26155118 TI - Decreased serum and mucosa immunoglobulin A levels in vitamin Aand zinc-deficient mice. AB - Simultaneous zinc and vitamin A deficiency are common health problems in developing countries. The objective of this study was to assess the effect of vitamin A- and zinc-deficient diet on immunoglobulin A (IgA) response. Six-week old mice were assigned into two groups receiving a normal vitamin A and zinc or low vitamin A and zinc diet for five months. Serum and intestinal mucosa IgA levels were determined by the enzyme-linked immunosorbent assay method. The concentration of zinc in serum was determined using an inductively coupled plasma mass spectrometer. Vitamin A measurement in serum was carried out by high performance liquid chromatography. Mice maintained on a low vitamin A and zinc diet showed significantly greater food intake but lower production of IgA both in serum and mucosa. A mucosa IgA level was significantly higher in both control and deficient groups than the serum IgA level. Results indicated that zinc and vitamin A deficiency is associated with a lower production of IgA. Micronutrient intervention strategies addressing IgA-related gastrointestinal infections are needed. PMID- 26155119 TI - Recombinant human interleukin receptor antagonist influences serum chemokines in patients with rheumatoid arthritis. AB - OBJECTIVE: To investigate the serum expressions of chemokines CCL2 and CCL3 in patients with rheumatoid arthritis (RA) who were treated with recombinant human interleukin 1 (IL-1) receptor antagonist (IL-1Ra). MATERIAL AND METHODS: Serum CCL2 and CCL3 were determined using an enzyme-linked immunosorbent assay in 54 active RA patients before and after treatment with IL-1Ra or a placebo, as well as 36 healthy controls. RESULTS: Compared with the healthy controls, all the 54 RA patients exhibited higher serum CCL2 and CCL3 before and after treatment (p < 0.05). However, patients who had a good response to IL-1Ra treatment had significantly lower mean changes in the serum CCL2 and CCL3 levels from baseline to the last injection than IL-1Ra non-responders (p < 0.01). CONCLUSIONS: CCL2 and CCL3 may be useful efficacy markers of IL-1Ra treatment. PMID- 26155120 TI - The effect of Zingiber officinale R. rhizomes (ginger) on plasma pro-inflammatory cytokine levels in well-trained male endurance runners. AB - The aim of this study was to investigate the effect of ginger on the concentrations of plasma interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in welltrained male endurance runners. To this end, twenty-eight high-level endurance runners were randomly assigned to two groups (control and experimental). They performed the same weekly training volume for 12 weeks. The Bruce treadmill test was used three days before the start of the 12-week training period and after weeks 6 and 12 to evaluate the physiological effects of training and ginger administration. After completing the first 6-week period of exercise training protocol, two groups received 500 mg capsules of ginger powder and placebo, respectively, three times a day for the second 6-week period. Blood samples were collected before (resting blood sample) and after the Bruce treadmill test. IL-1beta, IL-6 and TNF-alpha were assayed using standard commercial ELISA kits. Two-way repeated measures analysis of variance (ANOVA) was used to determine significant differences between control and experimental plasma IL-6, IL-1beta and TNF-alpha concentration means of pre- and post-test periods. The IL-1beta, IL-6 and TNF-alpha concentrations at the end of week 12/weeks 6 and 12 between two training groups were significantly different (p = 0.01, p = 0.01, and p = 0.01). In the experimental group alone, there were also significant differences in the mean IL-1beta, IL-6 and TNF-alpha concentrations at the end of weeks 6 and 12 (p = 0.01, p = 0.01, and p = 0.01). Our findings indicated that post-exercise plasma elevations of several pro inflammatory cytokines can be attenuated by a six-week ginger administration period. PMID- 26155121 TI - Periodontal disease in relation to selected parameters of the cardiovascular system in a group of patients with stable angina pectoris. AB - INTRODUCTION: Periodontal diseases (PD), which are the cause of chronic inflammatory processes, can develop increased susceptibility to vascular diseases through atherosclerosis. Due to the raised inflammatory and thrombotic risk, PD can have a significant influence on the course and results of stable angina pectoris (SAP). OBJECTIVES: The aim of the study is to evaluate the influence of chosen PD parameters on selected cardiovascular system parameters, and the correlation between chosen parameters of periodontitis and cardiovascular system parameters. MATERIAL AND METHODS: The case group included 67 patients with SAP, <= 60 years of age. The occurrence of well-known cardiovascular disease risk factors was evaluated on the basis of the clinical interview, clinical examination and laboratory tests. The occurrence of known risk factors for cardiovascular diseases (CVD) was established on the basis of the interview, clinical research and laboratory tests. Periodontal examination included API (approximal plaque index), CAL (clinical attachment level), PD (pocket depth), and BI (bleeding index). IMT (intima-media thickness) and the size of atherosclerotic plaque in carotid arteries were assessed by ultrasound examination. Segmental contractility abnormalities were assessed on the basis of echocardiography examination, presence of the single-vessel vascular and multi vessel vascular disease on the basis of angiographic examination. RESULTS: In the study group of patients, numerous risk factors and a higher level of API, CAL, PD and BI were observed. A higher prevalence of multi-vessel disease (75%) than single-vessel disease (25%) was noted on the basis of angiographic examination. Patients with contractility abnormalities demonstrated also poor oral cavity health. In addition, a higher concentration of CRP (3.2 mg/dl), fibrinogen (3.3 g/l)) and the progression of atherosclerosis, e.g. increased IMT (2.1 mm) and formation of atherosclerotic plaques were noted. Results of multivariate logistic regression demonstrated that API and PD had a significant influence on IMT. In patients with BMI >= 30 kg/m(2), the risk of increased IMT (OR = 4.67) was fourfold higher. SUMMARY: Periodontitis may influence the occurrence and course of the atherosclerotic process in persons with stable angina. PMID- 26155122 TI - Invasive candidiasis serological diagnosis in solid organ transplant recipients. AB - Solid organ transplant recipients are at high risk of fungal infections, because of ongoing immunosuppressive treatment. There are three post organ transplant phases: early, intermediate, and late, all of them at risk of Candida infections. Since conventional tests are insufficient, specific secondary diagnostic tests are still being explored. Serological tests are currently the most common choice. The present study was to determine the usefulness of mannan antigen and anti mannan antibody detection in diagnosing invasive candidiasis in liver or kidney transplant recipients. The levels of mannan and anti-mannan antibodies were assessed with Platelia Candida Ag Plus, and Platelia Candida Ab Plus (Biorad, Marne-la-Coquette, France) commercial tests, according to manufacturer's guidelines. Sixty six serum samples were obtained from 25 patients (9 liver transplant recipients, 7 kidney transplant recipients, and 9 patients prepared for a kidney transplant), 29 serum samples from 15 patients tested positive for mannan antigen. Serum samples were obtained from 14 patients tested positive for anti- mannan antibodies. Fungal antigen detection in blood serum in patients under immunosuppression, especially with neutropenia, suggests that antifungal treatment should be administered. Serological tests, especially mannan and anti mannan ones, are very useful for confirmation or exclusion of invasive candidiasis in high-risk patients. PMID- 26155123 TI - Serum trypsin and TCR as novel markers for predicting disease activity in IgG4 related disease. AB - BACKGROUND: IgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD. MATERIAL AND METHODS: A prospective cohort study of 22 patients with IgG4-RD was carried out from May 2009 to December 2012, and 65 cases with acute pancreatitis, 60 cases with pancreatic cancer and 120 healthy individuals were studied as controls. Serum TCR, trypsin and IgG4 levels were measured during pre- and post-treatment in the patients with IgG4-RD and their correlations with IgG4 were also assessed. RESULTS: Serum IgG4 and IgE levels in all patients were significantly increased, and tumor markers (carbohydrate antigen 19-9 and/or carbohydrate antigen 125) were also increased (12/22). Serum trypsin in patients with IgG4-RD was lower than in the ones with acute pancreatitis, pancreatic cancer, and healthy individuals. But serum TCR of IgG4-RD was significantly higher than in the pancreatic cancer group and normal controls and it was inversely correlated with the levels of IgG4 (r = -3.160, p = 0.042). CONCLUSIONS: The results indicate that serum TCR and trypsin might be useful markers for predicting disease activity in IgG4-RD. PMID- 26155124 TI - Immune mechanisms and the role of oxidative stress in intrahepatic cholestasis of pregnancy. AB - INTRODUCTION: The purpose of this study was to investigate levels of inflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and neopterin and oxidative stress status in patients with intrahepatic cholestasis of pregnancy (ICP) as well as their potential role in the pathophysiology. MATERIAL AND METHODS: Thirty patients with ICP (Group 1) and 30 healthy pregnant women (Group 2) were included in this prospective case-control study. Levels of IL-6, TNF-alpha and neopterin were determined in both of the groups. Total anti-oxidant status (TAS) and total oxidative stress (TOS) levels were determined by means of a fully automated Erel method. Oxidative stress index (OSI) was calculated as the ratio of TOS to TAS. RESULTS: There was no significant difference between the groups in IL-6 and TNF-alpha levels (p = 0.105 and p = 0.722, respectively). The mean neopterin level was significantly higher in Group 1 compared to Group 2 (2.34 +/-0.77 and 1.57 +/-0.38, respectively, p = 0.001). In addition, TAS, TOS and OSI levels were significantly higher in Group 1 (p = 0.004, p = 0.001 and p = 0.001, respectively) compared to Group 2. DISCUSSION: Intrahepatic cholestasis of pregnancy is an inflammatory disorder in which maternal immune reaction may play a role. Interleukin 6 and TNF-alpha, which are some of the markers of humoral reaction, act as an indicator of abnormal reaction rather than acute-phase reaction in ICP. Further clinical trials and supportive placental findings are needed on the role of cytokines in cellular and humoral immune reactions during the symptomatic period and delivery to better understand the role of immune mechanisms in the aetiology of ICP. PMID- 26155125 TI - Hypomethylation of interleukin 6 correlates with renal involvement in systemic lupus erythematosus. AB - OBJECTIVE: To analyze peripheral blood interleukin 6 (IL-6) methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE). MATERIAL AND METHODS: Blood samples from 41 adult patients with SLE, and 20 healthy controls were collected. The methylation status of IL-6 was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR. Correlations between IL-6 methylation status and clinical features or laboratory findings in patients with SLE were investigated. RESULTS: The methylation status and expression of IL-6 in peripheral blood could reflect the level in peripheral blood mononucleated cells (PBMCs) of SLE. Significantly positive correlation was found between IL-6 hypomethylation and renal disorder. Interleukin 6 hypomethylation was found negatively correlated with serum C3. CONCLUSIONS: The detection of IL-6 methylation status in peripheral blood could reflect the status in PBMC with SLE. Interleukin 6 may play a role in renal disorder with SLE patients. Interleukin 6 could be considered as a new biomarker for predicting SLE flare. PMID- 26155126 TI - Expression of CD11b and CD18 on polymorphonuclear neutrophils stimulated with interleukin-2. AB - BACKGROUND: Interleukin-2 (IL-2) is a lymphocyte-activating and growth-promoting factor, and has been widely studied on T-cells and NK-cells. However, the interaction of polymorphonuclear neutrophils (PMNs) with IL-2 is poorly studied and thus, this study aimed at defining IL-2 participation in the expression of CD11b and CD18 on PMNs. MATERIAL AND METHODS: PMNs were isolated from heparinized whole blood of healthy donors. Purified cells were incubated with IL-2 (10 ng/ml) for 24 hours at 37 degrees C in a humidified incubator with 5% CO2. After 24 hours' incubation, surface molecules (CD11b and CD18) were measured by flow cytometry. RESULTS: Interestingly, the antibodies of IL-2Rbeta chain (CD122-FITC) were found in all observed cells. The induction of CD11b mean fluorescence intensity (MFI) in highly purified PMNs stimulated with IL-2 was clearly increased recording 43% in comparison to the freshly isolated PMNs and the un stimulated PMNs which were found to be 23% and 28% of CD11b, respectively. Furthermore, flow cytometry analysis demonstrated that the highly purified PMNs exposed to IL-2 showed an increase in CD18 MFI, recording 47% with respect to that of the freshly isolated PMNs and PMNs cultured with the medium alone which showed a small amount of 38% and 27%, respectively. CONCLUSIONS: Results demonstrated that CD11b and CD18 had been acquired on the surface of the IL-2-in vitro-activated PMNs. These findings indicated that IL-2 may play a crucial role in PMNs migration. PMID- 26155127 TI - Enhancement of soluble CD28 levels in the serum of Graves' disease. AB - Graves' disease is an autoimmune disease of the thyroid gland mediated by T cells. CD28, a member of costimulatory molecules, plays a pivotal role in regulating T-cell responses. Plasma-soluble CD28 is one form of CD28 in peripheral blood. To investigate the concentrations of soluble CD28 in patients with Graves' disease, we used a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of CD28. Our results suggested that mean concentrations of soluble CD28 in plasma of patients with Graves' disease were 1.79 +/-1.52 ng/ml, and levels of soluble CD28 in healthy subjects were only 0.83 +/-1.35 ng/ml. Concentrations of soluble CD28 detected in patients with Graves' disease were significantly higher than those of healthy subjects (p < 0.01). Moreover, there was a significant positive correlation between the concentrations of soluble CD28 in plasma and levels of FT3 (r = 0.663), FT4 (r = 0.624) and TRAb (r = 0.728) in serum, but a negative correlation was found between sCD28 levels and TSH (r = -0.726). Through in vitro experiments we observed that engagement of soluble CD28 protein and B7-1/B7-2 molecules expressed on dendritic cells could exert the secretion of cytokine IL 6, which may promote the production of autoantibody and aggravate Graves' disease. Therefore, aberrant elevation of plasma-soluble CD28 in patients with Graves' disease may reflect the dysregulation of immune system, and may serve as a useful biomarker in Graves' disease diagnosis. PMID- 26155128 TI - Cytokine patterns in paediatric patients presenting serious gastrointestinal and respiratory bacterial infections. AB - In the adaptive immune response, the types of cytokines produced define whether there is a cellular (T1) or a humoral (T2) response. Specifically, in the T1 response, interleukin 2 (IL-2), interferon gamma (IFN-gamma) and tumor necrosis factor beta (TNF-beta) are produced, whereas in the T2 response, IL-4, IL-5, IL- 6, IL-10 and IL-13 are primarily produced. Cytokines are primarily involved in the regulation of immune system cells. The aim of the present study was to evaluate the cytokine patterns (Type 1/Type 2) and TNF-alpha expression levels in children with severe gastrointestinal and respiratory bacterial infections. The enzyme-linked immunosorbent assay (ELISA) technique was used to identify the cytokines and the infectious agents. The results obtained demonstrated that, in general, children with bacterial infections experienced an increase in IL-2, IFN gamma and IL-4 concentrations and a decrease in TNF-alpha, IL-5 and IL-6 concentrations when compared to healthy children. Specifically, type 1 cytokines and an increased TNF-alpha concentration were found in children with gastrointestinal infections. However, patients with respiratory infections showed increased concentrations of both T2 (IL-4, IL-6 and IL-10) and T1 (IL-2 and IFN gamma) components. Thus, it was concluded that children with gastrointestinal infections exclusively developed a T1 response, whereas children with respiratory infections developed a T1/T2 response to fight the infection. PMID- 26155129 TI - Serum level of eight cytokines in Han Chinese patients with systemic lupus erythematosus using multiplex fluorescent microsphere method. AB - AIM OF THE STUDY: To investigate the role of 8 cytokines and their correlation with clinical characteristics in systemic lupus erythematosus (SLE) in Han Chinese population by detecting their serum levels using the multiplex fluorescent microsphere method. MATERIAL AND METHODS: Serum was separated from 79 patients with SLE and 40 healthy controls. The serum cytokine detection was conducted according to the instruction of MILLIPLEX MAP human cytokine detection kit on the Luminex liquid phase array platform with 0.01 pg/ml detectable level. The 8 cytokines were interferon alpha2 (IFN-alpha2), IFN-gamma, interleukin 6 (IL 6), IL-8, IL-10, IFN-gamma-inducible protein 10 (IP-10), tumor necrosis factor alpha (TNF-alpha) and IL-17. Variable data were in skewed distribution and were expressed with median (P25, P75). Mann-Whitney analysis was used in statistical analysis. RESULTS: At the baseline level without any stimulus, the level of IP-10 expression was the highest among the 8 cytokines and the second highest was IL-8. The level of IL-17 was too low to be detected. The level of 7 cytokines was higher in SLE patients than in healthy controls (p < 0.01). The level of dsDNA antibody, C3, CRP, ESR and anti-nucleosome antibody was correlated with IL-10. Proteinuria was not correlated with any cytokine. CONCLUSIONS: Eight cytokines were measured in our study, while not all of them were detected. The most important finding was the usefulness of IL-10 as a disease activity biomarker for Han Chinese patient with SLE. None of cytokines reflected kidney injury. PMID- 26155130 TI - The effects of calcitriol with calcium carbonate supplementation on inflammatory biomarkers in chronic kidney disease patients' with low vitamin D. AB - INTRODUCTION: Chronic kidney disease (CKD) patients' are at risk of low vitamin D and chronic inflammation. We studied the effect of 12 weeks calcitriol and calcium carbonate supplementation on inflammatory mediators serum; interleukin-6 (IL-6), interleukin-10 (IL-10) and highly sensitive C-reactive protein (hs-CRP). MATERIAL AND METHODS: A prospective randomized study in CKD stages 2-4 with serum 25-hydroxyvitamin D (25-OHD) levels < 30 ng/ml. Patients were randomized into the Vitamin D + Calcium (Vitamin D + C) or Calcium group. Serums were analyzed at baseline, week 6 and 12. RESULTS: Fifty patients, median age of 53 (13.5) years were recruited. Their median IL-10 was 13.35 (25.22) pg/ml. At week 12, serum IL 6 was reduced in both groups (p = 0.001), serum IL-10 was maintained in the Vitamin D + C group (p = 0.06) and was reduced in the Calcium group (p = 0.001). CKD-diabetic patients had reduced serum IL-6 in both study groups (p = 0.001) and a reduction was seen in the Vitamin D + C group of the non-diabetics counterparts (p = 0.005). Serum IL-10 was reduced in the Calcium group (p < 0.05) whereas serum 25-OHD rose in both groups, regardless of their diabetic status (p < 0.05). CONCLUSIONS: Twelve weeks, calcitriol supplementation maintained IL-10, had no effects on hs- CRP and had no additional benefit compared to calcium carbonate in reducing serum IL-6 except in non-diabetics. PMID- 26155131 TI - Relationship between hypoalbuminemia, hyperlipidemia and renal severity in patients with lupus nephritis: a prospective study. AB - AIM OF THE STUDY: The purpose is to evaluate the relationship between hypoalbuminemia, hyperlipidemia, nephrotic and renal severity in patients with lupus nephritis. MATERIAL AND METHODS: Autoantibodies and serological parameters were measured and analyzed in 429 patients with lupus nephritis in a single centre. RESULTS: The prevalence for anti-dsDNA, anti-nucleosome and anti-histone was higher in the nephrotic syndrome (NS) patients than that in non-NS patients (p < 0.0001 for all comparisons). The NS patients had a higher proportion of diffuse proliferative renal lesions (69.05%) and membranous lesions (68.00%). Serum total cholesterol and albumin levels were associated with activity and severity of renal disease. The levels of proteinuria and serum albumin were positively correlated with activity and chronicity index (p < 0.001 for all correlations). The incidence of a poor renal outcome (p = 0.0461) in the NS patients was significantly increased. On the other hand, the remission rate (p = 0.0002) was significantly reduced and recurrence rate (p = 0.0027) was significantly increased in NS patients. CONCLUSIONS: This paper highlights that nephrotic-range proteinuria, elevated total cholesterol level and decreased serum albumin levels may reflect the activity and severity of renal damage in SLE patients. PMID- 26155132 TI - Possible role of complement factors and their inhibitors in the myocardial infarction: an immunohistochemical study. AB - Ongoing development of our civilization is accompanied by a marked increase of incidence of cardiovascular diseases and cardiovascular mortality. Ischemic heart disease with its extreme form - myocardial infarction - is one of the main problems of modern medicine. Despite much research devoted to this disease entity, its pathomechanism remains incompletely understood. Basing on research reports, more and more emphasis is put on immune reactions in the myocardium. Available literature lacks detailed studies examining the role of complement system and its inhibitors in the development and pathogenesis of myocardial infarction. Cells of ischemic myocardium were proven to become foreign antigens for the immune system of the patient's body. This results in complement activation of formation of so called membrane attacking complex that injures myocardial cells. By binding to its surface, it extends the myocardial destruction caused by the infarction itself. Results of immunochemistry studies presented in this paper have demonstrated the existence colocalization of complement components (C4d, C9) and membrane inhibitors (CD55, CD59) as well as soluble inhibitors (factor H) of the complement in the examined muscle tissue that underwent ischemic necrosis. Positive immunohistochemical reaction was found in the myocardial cells, intercellular matrix and blood vessels. PMID- 26155133 TI - Obesity, adipose tissue function and the role of vitamin D. AB - INTRODUCTION: Obesity is not just a cosmetic problem. Pathological accumulation of body fat can cause many health problems: insulin resistance, impaired glucose tolerance, and diabetes mellitus type 2. It may also increase morbidity and mortality. Adipose tissue plays an important role in body homeostasis by producing and secreting several bioactive proteins known as adipokines: adiponectin, leptin, resistin, visfatin, and apelin, which are involved in the regulation of food intake, glucose and lipid metabolism, and insulin action. There can be observed nutritional deficiencies, despite increased food intake, in morbidly obese people. Data concerning concentrations of serum 25(OH)D3 presented an inverse correlation with obesity parameters like: BMI (body mass index), waist circumference, fat mass or percentage of body fat. Also, higher insulin sensitivity was associated with higher concentrations of vitamin D. CONCLUSIONS: Studies published up to now suggest that vitamin D plays an important role in adipose tissue function and could be involved in the synthesis and modulation of adipokine production. This article is a review of the literature on fatty tissue function and the role of vitamin D in obesity. PMID- 26155134 TI - Dendritic cell-glioma fusion activates T lymphocytes by elevating cytotoxic efficiency as an antitumor vaccine. AB - BACKGROUND: Hybrid cells produced by fusions of tumor and dendritic cells (DC) have demonstrated remarkable efficacy for priming the anti-tumor immune response. In the current study, we examined the antitumor activity of cytotoxic T lymphocytes (CTLs) primed in response to a tumor vaccine comprising a glioma-DC fusion as part of a therapeutic against glioma. MATERIAL AND METHODS: Primary cultured glioma cells were fused with peripheral blood DC under conditions of polyethylene glycol (PEG) incubation. Glioma cell suspensions were designated as three groups to include (1) CTL-effective cell group activated by fused cells; (2) CTL-effective cell group stimulated by co-cultured glioma cells and DC cells; and (3) lymphocyte-only group as a control, which was not stimulated by the DC. Cytotoxicity of CTLs on glioma cells was accessed by MTT assay in vitro. RESULTS: Glioma cells with peripheral blood DC were cultured and fused. The killing effect of CTLs pre-activated by fused cells was significantly higher than that of the co culture CTL group with unsensitized lymphocytes (p < 0.01). The killing activity, as measured by an enhanced efficiency ratio, was increased significantly in the co-cultures of fused cells with CTL groups (p < 0.01). CONCLUSIONS: The glioma dendritic cell fusion vaccine possessed a more effective anticancer activity by stimulating the effector activity of CTLs. PMID- 26155135 TI - Cytokine signatures of human whole blood for monitoring immunosuppression. AB - How to evaluate status of the immune system is extremely critical for clinical immunosuppressive treatment. In this study, we tested the secretion of cytokines in undiluted whole blood samples stimulated with Phorbol 12-myristate 13-acetate (PMA) and ionomycin (IONO), and compared the effects of dexamethasone (DEX), cyclosporine A (CsA) or mycophenolic acid (MPA), either alone or in combination, on cytokine profiles. The results showed that both DEX and CsA dose-dependently inhibited the production of eleven cytokines: interleukin (IL)-2, IL-4, IL-5, IL 6, IL-13, IL-17, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Unexpectedly, MPA showed no obvious influences except for the mild inhibition on GM-CSF production. In combination treatment, cytokine profiles reflect not only the synergistic effects among drugs, but also the specific effect of the individual drug. Thus, the effects of different immunosuppressants could be reflected through their specific cytokine signatures, which can be applied to maximize immunosuppressive effects, while to minimize risk of infections and help physicians to reasonably apply immunosuppressants. PMID- 26155136 TI - Xenotransplantation of human cultured parathyroid progenitor cells into mouse peritoneum does not induce rejection reaction. AB - INTRODUCTION: Parathyroid progenitor cells devoid of immunogenic antigens were used for human allotransplantation. Although there were many potential reasons for the expiry of transplant activity in humans, we decided to exclude a subclinical form of rejection reaction, and test the rejection reaction in an animal model. MATERIAL AND METHODS: Experiments were carried out on 40 conventional male mice in their third month of life. The animals were housed in groups of 10 per cage in 4 cages with fitted water dispensers and fed a conventional diet based on standard pellet food. They were divided into four groups of 10 animals each, three experimental groups and one control group. Identified progenitor cells were stored in a cell bank. After testing the phenotype, viability, and absence of immunogenic properties, the cells were transplanted into mouse peritoneum cavity. RESULTS: Animals were observed for 9 weeks. At 9 weeks of observation, the mean serum PTH concentration in the experimental groups was 2.0-2.5 pg/ml, while in the control group it did not exceed 1.5 pg/ml. The immunohistochemical assays demonstrated that millions of viable cells with a phenotype identical to the endocrine cells had survived in the peritoneum. Histologic specimens from different internal organs stained for PTH revealed positive cells labelled with anti-PTH Ab in the intestinal lamina, brain, liver, and spleen. CONCLUSIONS: In the present paper we have demonstrated that xenotransplantation may be used as a model for an explanation of the immunogenic properties of cells generated from postnatal organs for regenerative therapy. PMID- 26155137 TI - Use of laser microdissection in the analysis of renal-infiltrating T cells in murine lupus. AB - OBJECTIVE: To clarify the role of T cells in kidney pathology of three widely used murine lupus models. MATERIAL AND METHODS: Cells infiltrating the glomeruli and perivascular areas in MRL/lpr (n = 10 female), NZB* NZW F1 (B/W F1) (n = 9 female), and BXSB (n = 10 male) mice were captured by laser microdissection (LMD). Samples were subjected to nested reverse transcription polymerase chain reaction (RT-PCR) with primers specific to beta-actin, T-cell receptor beta chain (TCR-Cbeta), interleukin (IL)-10, IL-13, IL-17, and interferon-g (IFN-gamma). Frozen sections of lesions were also stained immunohistochemically for tissue and cellular characterization. RESULTS: T cells infiltrating the glomeruli and perivascular areas predominantly produced IFN-gamma, IL-13, and IL-17 in MRL/lpr, B/W F1, and BXSB mice, with IL-17 expression in glomeruli of BXSB mice being significantly lower than that of MRL/lpr and B/W F1 mice. IL-10 was detected only in the perivascular areas of MRL/lpr and B/W F1 mice and not in glomeruli isolates. Immunohistochemical staining revealed positive for the expression of Thy-1, CD4, CD8, and B220 in glomeruli and perivascular areas from all three strains of mice. CONCLUSIONS: Cytokine balance in murine SLE is complex and cannot be attributed simply to the balance between Th1 and Th2 cells. Th17 cells may play a critical role in disease pathology, possibly with greater contribution toward disease progression in MRL/lpr and B/W F1 mice than in BXSB mice. Furthermore, these findings lend support to the concept that different molecular mechanisms underlie glomerulonephritis as compared to vasculitis. PMID- 26155138 TI - Effects of the recombinant allergen rDer f 2 on neuro-endocrino-immune network in asthmatic mice. AB - Severe and life-threatening side effects can occur in patients receiving allergen specific immunotherapy (SIT), and recombinant allergens made from cDNA have been used in clinical trials for ten years and appear promising for SIT. The aim of this study is to explore the effects of the recombinant allergen Der f 2 (the group 2 allergen from Dermatophagoides farinae) on the neuro-endocrino-immune network in asthmatic mice. Twenty-eight mice were divided into four groups - A, B, C and D. To induce asthma, a crude extract of D. farinae was injected intraperitoneally into the mice in groups B, C and D. Later, the crude extract or recombinant allergen rDer f 2 was given to groups C and D, respectively. Normal saline was given to groups A and B. Serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), interleukin 4 (IL-4), and interferon gamma (IFN-gamma) were detected by immunoassay and the pathological change of lung tissue was observed by hematoxylin and eosin (HE) staining. Serum CRH, ACTH, CORT, and IFN-gamma were highest in healthy group A but lowest in asthma group B. Treatment with the crude extract or recombinant allergen rDer f 2 significantly attenuated this response in asthmatic mice, but there was no difference between the two treatments (p > 0.05). Serum IL-4 was elevated in asthma group B but lowest in healthy group A. Treatment with the crude extract or recombinant allergen rDer f 2 significantly attenuated this response in asthmatic mice, but there was no significant difference between the two treatments (p > 0.05). However, lung pathology as measured histologically (Underwood Score) showed that rDer f 2-treatment was significantly better than crude extract treatment (p < 0.05). In brief, recombinant allergen Der f 2 can strengthen the function of hypothalamus-pituitary-adrenal (HPA) axis, affect the balance of Th1 and Th2 cytokines, and reduce pulmonary inflammation in asthmatic mice. PMID- 26155139 TI - Effects of sufentanil on human gastric cancer cell line SGC-7901 in vitro. AB - Sufentanil is a new kind of opioid analgesic and acts on MU opioid receptor. In this study, we aim to investigate the effects of sufentanil on gastric cancer cell line SGC-7901, after being exposed to different concentrations of sufentanil. Gastric cancer cells were exposed to sufentanil for a predetermined time at concentrations of 0, 0.5, 5, 50 and 500 nmol/l, respectively. Cell viability at different time points after exposure to sufentanil was tested by CCK 8 assay. FDA-PI staining was used to observe membrane integrity of gastric cancer SGC7901 cells. The apoptosis of gastric cancer cells was analyzed by Annexin V FITC/PI Flow Cytometry and the changes of the cell cycle was determined by a detection kit. As a result, cell viability decreased in a dose- and time dependent manner. Furthermore, with the concentration of sufentanil increased, the proportion of dead and apoptotic SGC-7901 cells increased, and more cells were arrested in G2/M phase. In a word, sufentanil can inhibit the cell viability and induce the apoptosis of gastric cancer SGC-7901 cells in vitro. PMID- 26155140 TI - Diet-induced obesity mediates a proinflammatory response in pancreatic beta cell via toll-like receptor 4. AB - Toll-like receptor 4 has an important role in inflammation and immunity. Whether TLR4 signaling contributes to the link between insulin resistance and islet beta cell dysfunction is an unanswered question. Here, we show that in the face of the same high-fat continuous stimulation for 24 weeks, in TLR4-/- HF mice, the weight, fraction of the liver, epididymal fat pad fraction, as well as blood glucose and insulin levels were lower than in the WT HF group. In TLR4-/- HF mice, the O2 consumption, CO2 production and activities were higher than in the WT HF group. Glucose tolerance test, insulin tolerance test and insulin release test suggest that the impaired insulin secretion was significantly improved in TLR4-/- HF mice, compared with the WT HF group. In TLR4-/- HF mice, islet beta cell ultrastructure was not damaged in the face of the same high-fat continuous stimulation, compared to that in the WT HF group. By detecting glucose-stimulated insulin secretion in the primary islet, insulin secretion of TLR4-/- HF mice was better than that of the WT HF group, and in the TLR4-/- HF group, at the mRNA level, islet interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein 1 (MCP-1) were significantly lower than in the WT HF group. There was the islet macrophage infiltration in the WT HF group, but no significant macrophage infiltration in the TLR4-/- HF group. These data suggest that the damaged islet functions of the high fat diet-induced obesity mice may be linked to the TLR4 expression level, and the recruitment of macrophages into the islets. PMID- 26155141 TI - Acute meningitis in rats is associated with decreased levels of miR132 and miR146a. AB - INTRODUCTION: The pathogenesis of bacterial meningitis due to Streptococcus pneumoniae is still unclear. Despite early treatment with antibiotics, its morbidity and mortality is still high. MATERIAL AND METHODS: Streptococcus pneumoniae induced rat meningitis models were taken and divided into 2 groups; control (C) and meningitis (M). Western blot was used to detect toll like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-alpha), interleukin 1B (IL1B), nuclear factor kappaB (NFkappaB) and real time polymerase chain reaction were used to detect the expression of miR146a, miR132, respectively. RESULTS: We found that the expressions of TLR4, TNF-alpha, IL1B, NFkappaB were all up regulated in the acute stage of bacterial meningitis when compared to the control group. While for the post transcription factors, miR146a and miR132, the opposite was observed. They were down-regulated in the meningitis group. CONCLUSIONS: miR146a and miR132 may take part in the pathogenesis of SP bacterial meningitis as well as the TLR4- NFkappaB- TNF-alpha/IL1B signal transduction pathway. PMID- 26155142 TI - Analysis of humoral immune response of animals exposed to bacterial antigens. AB - From the Aeromonas hydrophila strain, five different types of antigens such as heat killed antigen, whole cell antigen, heat killed antigen with antiserum, whole cell antigen with antiserum and nucleotide antigens were prepared and injected into the experimental fish (Catla catla) groups for the study of immunomodulation. Analysis of immunogenicity of antigens against the fish Catla catla was estimated. The A. hydrophila produced beta hemolytic pattern on the blood agar plate. B lymphocyte counts using rosette forming assay revealed a significant decrement in pathogens exposed fishes as compared to controls. Fishes exposed to pathogenic strains (1/10(th) sublethal concentration) for 3 weeks showed a reduction in PFC. The effect or pathogenic antigens in direct spleenic plaque forming cells (1 g M producing cells) showed a reduction in the secondary plaque forming cell in the first 3 weeks and a time- and dose-dependent decrease in primary and secondary PFC response. A remarkable observation enhancement in B cell production due to immune complex of antigens was noted in the present study. The enhancement of this type of immune responses confirms the potential of immune complexes to be used as vaccines. PMID- 26155143 TI - Application of flow cytometry in diagnosing lymphomas in dogs and cats. AB - Classification of types of lymphomas is done by interpreting cell morphology results obtained in cytological and/or histological examinations. In recent years, additional methods like immunocytochemistry (ICC), immunohistochemistry (IHC), immunophenotyping by flow cytometry and polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR), have been used to diagnose and classify lymphomas. Unfortunately, none of these methods is completely specific and sensitive. Thus, a combination of several diagnostic methods or use of all available techniques allows for evaluation of morphological properties of cells like their maturity and diversification. Owing to the use of sets of antibodies it is possible to identify the phenotype of hyperplastic cells as well as their origin. Combination of results obtained through phenotypical analysis with flow cytometry examination with morphological, histological and genetic testing enables a detailed analysis of, in this case, lymphoproliferative diseases including reaction changes, primary and secondary immunological deficits as well as autoimmune diseases. PMID- 26155144 TI - Cutaneous expressions of interleukin-6 and neutrophil elastase as well as levels of serum IgA antibodies to gliadin nonapeptides, tissue transglutaminase and epidermal transglutaminase: implications for both autoimmunity and autoinflammation involvement in dermatitis herpetiformis. AB - INTRODUCTION: Dermatitis herpetiformis (DH) seems to be a chronic immune-mediated inflammatory disease of partially known origin. In light of its known biological functions and its involvement in tissue pathology in other disease states, particularly in nickel-induced allergic contact dermatitis coexisting with DH, it would appear that the central and peripheral response by neutrophils and their mediators (e.g. neutrophil elastase - NE) in DH may be partially mediated by interleukin-6 (IL-6). The aim of the study was to assess the role of IL -6 in DH lesions by examining the relationships between IL -6/NE cutaneous expression and levels of serum anti-nonapeptides of gliadin (npG) IgA, anti-tissue transglutaminase (tTG) immunoglobulin A (IgA), anti-epidermal transglutaminase (eTG) IgA in DH. MATERIAL AND METHODS: In total, 24 DH patients having IgA cutaneous deposition were studied. Immunohistochemistry on paraffin-embedded sections with quantitative digital morphometry was used to measure the intensity of IL -6 and NE cutaneous expressions. Levels of serum anti-npG IgA, anti-tTG IgA and anti-eTG IgA were evaluated with ELISA. RESULTS: We found no statistically significant correlation between the NE and IL -6 expression intensities. Our results revealed also a lack of correlations between NE/IL -6 expressions and levels of anti-npG IgA, anti-tTG IgA, anti-eTG IgA in DH. However, the IL -6 expression level was significantly lower than that of NE. CONCLUSIONS: The lack of correlations suggested no substantial interactions between IL -6, NE, IgA/npG, IgA/tTG or IgA/eTG in DH. Presented results might indicate the heterogenetic nature of DH pathogenesis suggesting further that both autoimmune and autoinflammatory phenomena may be involved in DH cutaneous pathology. PMID- 26155145 TI - CD4+CD25(high), CD8+CD28- cells and thyroid autoantibodies in breast cancer patients. AB - AIM OF THE STUDY: To investigate the percentage of CD4+CD25(high) cells (including Treg cells) and CD8+CD28- cells in breast cancer patients with and without high levels of autoimmune thyroid antibodies. MATERIAL AND METHODS: Thirty-five women with breast cancer (9 of them having high thyroid antibodies) and fourteen healthy subjects were enrolled in this study. Flow cytometry was used to count CD4+CD25(high) cells and CD8+CD28- suppressive cells (CD8 cell subtypes). RESULTS: In the patient group, the percentage of CD28- cells in CD8+ lymphocytes were higher [67.50% (55.1180.33) vs. 51.56% (42.5766.38); p = 0.021] and the percentage of CD28+CD45RO- cells (memory cells) in CD8+ lymphocytes were lower than in the control group. CD4+CD25(high) cell percentage in CD4+ lymphocytes was elevated in the patient group [6.44% (4.528.74) vs. 2.97% (1.724.34); p < 0.001]. When the cytometric parameters were compared between patients (with high vs. normal thyroid antibodies), the distribution of CD8+ cell subgroups was also similar. CD4+CD25(high) cells among CD4+ lymphocytes were decreased in patients with high levels of thyroid antibodies [5.19% (3.426.17) vs. 6.99% (4.829.95); p = 0.043]. CONCLUSIONS: CD4+CD25(high) cells may play a role in autoimmunity of breast cancer patients, and may be a predictive marker. Advanced studies which evaluate the possible links between regulatory cells and autoimmunity should be established in cancer patients. PMID- 26155146 TI - Abnormal levels of age-elastin derived peptides in sera of diabetic patients with arterial hypertension. AB - INTRODUCTION: An important factor in vascular wall alterations is degradation of elastic fiber major protein - elastin. As a result, elastin derived peptides (EDP) are found in circulation. Advanced glycation might also involve elastin, because it is a protein with slow metabolism. The aim of our study was to measure serum levels of glycated elastin derived peptides (AGE-EDP) of elastin in patients with type 2 diabetes mellitus (T2DM) and arterial hypertension (AH). MATERIAL AND METHODS: We adapted an ELISA technique for the determination of AGE EDP. Sera of 93 patients with T2DM and AH (mean age 61.4 +/-11.3 years, diabetes duration 9.88 +/-3.12 years; hypertension duration 9.28 +/-4.98) were tested. These values were compared to 42 age- and sex-matched controls. Diabetics were divided in two groups according to presence - Group 1 (n = 67) or absence - Group 2 (n = 26) of microangiopathy. RESULTS: Patients with T2DM and AH showed statistically significantly higher levels of AGEEDP in comparison with healthy controls 0.060 (0.053/0.065) vs. 0.039 (0.031/0.044) (KW = 35.2; p < 0.0001). Group 1 showed significantly higher levels of AGE-EDP than the control group 0.069 (0.051/0.070) vs. 0.039 (0.031/0.044) (KW = 33.0; p < 0.0001). Group 2 also showed significantly higher levels of AGE-EDP than controls 0.058 (0.049/0.064) vs. 0.039 (0.031/0.044) (KW = 22.1; p < 0.0001). AGE-EDP showed a correlation with an insulin dose (r = -0.28; p = 0.05), systolic blood pressure (r = 0.25; p = 0.01), BMI (r = 0.39; p = 0.01) and retinopathy (r = 0.18; p = 0.05). CONCLUSIONS: The measurement of non-invasive markers of elastin glycation may be useful in monitoring development of vascular wall alterations and therapeutic interventions. PMID- 26155147 TI - Bouquet variety of antiphospholipid antibodies in recurrent pregnancy loss. AB - Seventy-six female patients with two or more recurrent pregnancy losses (RPL) during the 1(st) trimester were studied. Based on the results of the aCL and aB2GPI antibodies testing, patients were divided in two groups: 22 patients with RPL and elevated immunoglobulin (Ig) G/IgM aCL and/or aB2GPI [RPL + antiphospholipid syndrome (APS)] and 54 patients with RPL alone (without high antibodies). Immunoglobulin G aPS and IgG a-AnV in patients with RPL + APS were higher than in controls and IgG aPS were higher in RPL + APS than in RPL alone. Additionally IgG a-AnV and IgM aPE are higher in RPL alone than in controls. In 18/22 (81%) patients with RPL + APS and 29/54 (54%) patients with RPL alone, there were one or more positive antibodies: aPS, aPT, a-AnV or aPE. These results raise a question whether or not these antiphospholipid antibodies should be routinely tested in women with RPL and especially in the context of the so-called "seronegative APS". PMID- 26155148 TI - Elastase and metalloproteinase-9 concentrations in saliva in patients with chronic periodontitis. AB - Elastase and metalloproteinase-9 (MMP-9) are two of numerous proteolytic enzymes released by neutrophilic granulocytes in the course of periodontitis. The aim of the study was to determine the concentrations of elastase and MMP-9 in saliva in patients with chronic periodontitis compared to healthy individuals. The enzyme linked immunosorbent assay method was employed to determine the concentrations of elastase and MMP-9 in saliva in patients with chronic periodontitis and with pocket depth (PD) >= 6 mm and PD < 6 mm, as well as in saliva of healthy individuals. Significantly higher concentrations of elastase and MMP-9 were observed in patients with periodontitis compared to healthy individuals (p < 0.01). Also a significant difference in elastase concentration in saliva was observed between the PD >= 4 mm and PD < 6 mm groups and between the PD >= 6 mm and control groups, and statistically significant differences in MMP-9 concentrations between the PD >= 6 mm and control groups. No statistically significant differences were observed between the PD < 6 mm and control groups for elastase concentrations in saliva as well as between the PD >= 6 mm and PD < 6 mm groups, and also between the PD < 6 mm and control groups for MMP-9 concentrations in saliva. Elastase and MMP-9 concentrations in saliva can be considered as biochemical indicators of severity of periodontitis. PMID- 26155149 TI - The effect of aerobic training on CXL5, tumor necrosis factor alpha and insulin resistance index (HOMA-IR) in sedentary obese women. AB - The purpose of the present study was to investigate the effects of a 12-week training program on serum CXC ligand 5, tumor necrosis factor alpha (TNF-alpha) and insulin resistance index in obese sedentary women. To this end, twenty-four obese sedentary women were evaluated before and after a 12-week exercise program including a brief warm-up, followed by ~45 min per session of aerobic exercise at an intensity of 60-75% of age-predicted maximum heart rate (~300 kcal/day), followed by a brief cool down, five times per week. After the exercise program, body weight, waist circumference, waist to hip ratio, percentage body fat mass, fasting glucose and insulin of participants were decreased. Furthermore, serum CXCL5 levels were significantly decreased from 2693.2 +/-375.8 to 2290.2 +/-345.9 pg/ml (p < 0.001) after the training program, which was accompanied with significantly decreased HOMA-IR (p < 0.001) and TNF-alpha (p < 0.001). Exercise training induced weight loss resulted in a significant reduction in serum CXCL5 concentrations and caused an improvement in insulin resistance in obese sedentary women. PMID- 26155150 TI - Expression of interleukin-17 in lesions of erythema multiforme may indicate a role for T helper 17 cells. AB - INTRODUCTION: The aim of this study was to evaluate levels of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-17A and interferon gamma (IFN-gamma) in the serum of patients with erythema multiforme (EM) and to search for the presence of IL-17 expressing cells in lesional samples of EM. MATERIAL AND METHODS: A total of 32 patients (22 females and 10 males) diagnosed with EM of the minor or major type were included in the study. Levels of IL-2, IL-6, IL-8, IL-10, IL-17A and IFN gamma in the serum were determined and compared with healthy controls. Biopsy specimens were stained with haematoxylin and eosin (HE) and monoclonal antibodies to CD4, CD8 and IL-17 for immunohistochemical examination. RESULTS: IL-2, 6, 8 and 17A were significantly higher in the patient group (p = 0.016, p = 0.001, p = 0.004, p = 0.006, respectively) and levels of IL-10 were significantly lower than in the control group (p = 0.046). The cellular infiltrate in lesions of EM was composed mainly of CD4+ T lymphocytes. The presence of IL-17-expressing cells, at proportion of 5 to 50%, was observed in the infiltrate. CONCLUSIONS: The demonstration of IL-17-expressing cells in lesions of EM in this study has brought forth the assumption that Th17 cells may be involved in the pathogenesis of EM. PMID- 26155151 TI - Impact on red blood cell immunity patterns in postoperative phase following total hip arthroplasty. AB - OBJECTIVE: In this study, we aimed to measure changes in red blood cell (RBC) immunity and cytokine levels after performing total hip replacement surgery. MATERIAL AND METHODS: Twenty patients receiving total hip arthroplasty were investigated by measuring presurgical and postoperative RBC natural tumor erythrocyte rosette rate (NTERR), RBC C3b receptor rosette rate (RC3bRR), RBC membrane CD35, CD58 and CD59 expression and cytokine levels [including tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN gamma), interleukin 10 (IL-10) and prostaglandin E2 (PGE2)]. Blood samples were collected on the day before surgery and on the first day after hip arthroplasty. RESULTS: Postoperative NTERR and RC3bRR were significantly lower than presurgical levels (p < 0.05). The RBC membrane CD35, CD58 and CD59 expressions were significantly decreased in the postoperative phase compared to pre-operative levels. Importantly, RBC promoting lymphocyte proliferation rates were significantly reduced after surgery. In addition, postoperative TNF-alpha, IL-2 and IFN-gamma levels in RBC and lymphocyte culture fluid were lower than those pre-operation, whereas IL-10 and PGE2 were significantly increased compared to presurgical levels (p < 0.05). CONCLUSIONS: The modification of RBC immune function may be involved in the occurrence and development of the infection following hip arthroplasty, and this suggests a novel strategy to prevent such infection. PMID- 26155152 TI - Interleukin-18 and NGAL in assessment of ESWL treatment safety in children with urolithiasis. AB - Urolithiasis is recurrent chronic disease and a complex nephro-urological problem. Currently it is diagnosed in very young children, even infants in the first quarter of life. Until recently the main method of treatment for stones, which for various reasons did not pass spontaneously, was open surgery. At present, the main method replacing open surgery is extracorporeal shock wave lithotripsy (ESWL). Usefulness of common known indicators of the renal function to assess the safety of ESWL procedure is evaluated and verified. The basic markers are serum creatinine, cystatin C, urea, glomerular filtration rate and albuminuria assessment. Unfortunately all these methods show little sensitivity in the case of acute injury processes. There are efforts to use new biomarkers of renal tubular activity, which include among others interleukin 18 (IL-18) and neutrophil gelatinase-associated lipocalin (NGAL). The aim of the study was to assess the safety of ESWL by means of albumin to creatinine ratio, serum cystatin C levels and concentration of two new markers: IL -18 and NGAL. Albumin to creatinine ratio (p = 0.28) and serum cystatin C (p = 0.63) collected before and 48 hours after ESWL did not show statistically significant differences. Similarly, both new markers (IL -18 and NGAL) showed no significant differences (urine IL -18 p = 0.31; serum NGAL p = 0.11; urine NGAL p = 0.29). In conclusion, serum cystatin C tests, urine albumin to creatinine ratio and new early markers of renal tubular injury confirmed the safety of the extracorporeal shock wave lithotripsy (ESWL) and show that the procedure does not cause any episode of acute renal injury. PMID- 26155153 TI - Cytomegalovirus pneumonia as the first manifestation of severe combined immunodeficiency. AB - Severe combined immunodeficiency (SCID) is characterized by the absence of functional T lymphocytes and impairment of adaptive immunity. While heterogeneity of the genetic background in SCID leads to the variability of immune phenotypes, most of affected newborns appear healthy but within the first few months they develop life-threatening opportunistic respiratory or gastrointestinal tract infections. The objective of the study was to define the presenting features and etiology of infections in children with SCID. We retrospectively reviewed five children in whom the diagnosis of SCID had been established in our pediatric immunology clinic over the last 10-year period. A viral respiratory tract infection was the first manifestation of SCID in all the children studied. Cytomegalovirus (CMV) pneumonia was recognized in as many as 4 cases and coronavirus pulmonary infection was diagnosed in one case, whereas Pneumocystis jiroveci was identified as a co-pathogen in one CMV-infected patient. Severe combined immunodeficiency is a pediatric emergency condition and given the significant impact of pulmonary CMV infection in SCID children, establishing an accurate etiological diagnosis is of essential importance in instituting the specific treatment and improving the outcome. PMID- 26155154 TI - Celiac disease as an autoimmune condition. AB - Autoimmune diseases have become a major medical problem of recent years. Celiac disease is an autoimmune disease model. The aim of our study was to follow the changes in the clinical autoimmunity picture of the celiac disease from recent years. The study of autoimmunity in celiac disease has focused on associated diseases with the aforementioned disease: type 1 diabetes mellitus, thyroid autoimmunity disease, Graves' disease, Hashimoto's disease, systemic lupus erythematosus, systemic sclerosis, spondyloarthritis, hyperprolactinemia, Turner syndrome, Addison's disease, sensory neuronopathies. Immune reactivity to tissue transglutaminase targeted autoantibodies and other autoantigens, including transglutaminase 3, actin, ganglioside, collagen, calreticulin or zonulin which have been reported in the celiac disease. New research directions given by celiac disease autoimmunity, interleukin 1, interleukin 2, protein tyrosine phosphatase non-receptor type 22, CD4+CD25+ T lymphocytes, cytotoxic T-lymphocyte antigen 4, infection with Necator americanus and definitive identification of pathogenic T cell epitopes, seem to provide a solution in celiac disease treatment. PMID- 26155156 TI - An anti-DEC-205 monoclonal antibody stimulates binding of thymocytes to rat thymic dendritic cells and promotes apoptosis of thymocytes. AB - DEC-205, a transmembrane receptor responsible for cross-presentation of apoptotic cell-derived antigens, is expressed by cortical thymic epithelial cells (TEC) and thymic dendritic cells (TDC) in humans and mice, but its function in T-cell development is still unclear. In this work we have studied for the first time the expression of DEC-205 in the rat thymus by HD83 monoclonal antibody (mAb) and immunohistochemistry, as well as the ability of this mAb to modulate thymocyte - TDC interactions in vitro. We showed the positivity of cortical TEC in situ, including thymic nurse cells (TNC) in suspension, and TDC, whereas subcapsular, perivascular and medullary TEC were negative. All examined DEC-205 positive and DEC-205 negative structures were MHC class II positive. HD83 mAb increased apoptosis of thymocytes in co-culture with TDC in vitro and the process was associated with increased binding of thymocytes to TDC in a rosette form. Since negative selection of thymocytes by clonal deletion (apoptosis) was mediated predominantly by TDC, our results suggest the possible indirect effect of the DEC 205 molecule in these mechanisms. PMID- 26155155 TI - Immunosuppressive therapy in allograft transplantation: from novel insights and strategies to tolerance and challenges. AB - Immunosuppression therapy is the key to successful post-transplantation outcomes. The need for ideal immunosuppression became durable maintenance of long-term graft survival. In spite of current immunosuppressive therapy regimens advances, surgical procedures, and preservation methods, organ transplantation is associated with a long-term poor survival and significant mortality. This has led to an increased interest to optimize outcomes while minimizing associated toxicity by using alternative methods for maintenance immunosuppression, organ rejection treatment, and monitoring of immunosuppression. T regulatory (Treg) cells, which have immunosuppressive functions and cytokine profiles, have been studied during the last decades. Treg cells are able to inhibit the development of allergen-specific cell responses and consequently play a key role in a healthy immune response to allergens. Mature dendritic cells (DCs) play a crucial role in the differentiation of Tregs, which are known to regulate allergic inflammatory responses. Advance in long-standing allograft outcomes may depend on new drugs with novel mechanisms of action with minimal toxicity. Newer treatment techniques have been developed, including using novel stem cell-based therapies such as mesenchymal stem cells, phagosomes and exosomes. Immunoisolation techniques and salvage therapies, including photopheresis and total lymphoid irradiation have emerged as alternative therapeutic choices. The present review evaluates the recent clinical advances in immunosuppressive therapies for organ transplantation. PMID- 26155157 TI - The influence of vitamin B12 supplementation on the level of white blood cells and lymphocytes phenotype in rats fed a low-protein diet. AB - Protein malnutrition has a negative effect on body composition and some blood parameters, especially in the young growing organism. One of nutritional factors which could protect against negative consequences of protein deficiency may be B group vitamins. The aim of the study was to investigate the effect of vitamin B12 supplementation on the immune system in rats fed a standard and a low-protein diet. Rats were fed a control (20% of energy from protein) or a protein-deficient diet (4.5% of energy from protein). Half of animals in each group were additionally supplemented with vitamin B12 (300% of the daily intake). The white blood cells analysis and lymphocytes immunophenotyping (number and percentage) were performed. Low-protein diets caused disturbances in WBC and lymphocyte subpopulations in both short- (30-day) as well as long-term periods (90-day). Vitamin B12 supplementation significantly reduced the negative impact of protein malnutrition after 30 days, however had no effect on long-term malnutrition. Furthermore, vitamin B12 addition in rats fed a control diet did not affect the studied parameters. This observation opens the promise of use of vitamin B12 supplementation to improve immune system parameters in protein malnourished organisms. PMID- 26155158 TI - Additive anti-allergic effects of anti-interleukin-33 and anti-Siglec-F treatments in a murine model of allergic asthma. AB - BACKGROUND: Anti-interleukin-33 (anti-IL-33) and anti-Siglec-F antibodies have potent anti-allergic effects on murine allergic asthma and rhinitis and induce eosinophil apoptosis. OBJECTIVE: We aimed to determine whether post-sensitization with anti-IL-33/anti-Siglec-F treatments exhibited more potent effects compared to individual treatments in a murine allergic asthma model. MATERIAL AND METHODS: Twenty-five BALB/c mice were separated into five groups (n = 5): Group A (control), Group B (ovalbumin [OVA] challenge), Group C (OVA + anti-IL-33), Group D (OVA + anti-Siglec-F), and Group E (OVA + anti-IL-33 + anti-Siglec-F). Serum total/ OVA-specific IgE, bronchoalveolar lavage (BAL) inflammatory cells and cytokines (IL-4 and IL-5), histopathological lung properties, and airway hyperreactivity were compared. RESULTS: Ovalbumin challenge induced strong immune and inflammatory responses with > 6-fold IgE level increases; 10- to 25-fold BAL eosinophil, neutrophil, and lymphocyte count increases; and > 1.5-fold IL-4 and IL-5 level increases (p < 0.05). Whereas anti-IL-33 reduced neutrophil counts, anti-Siglec-F and anti-IL-33/anti-Siglec-F reduced both eosinophil and neutrophil counts (p < 0.05). Individual treatments reduced OVA-mediated bronchiolar infiltration by 50% (p <0.05). Ovalbumin challenge increased airway hyperreactivity by 4-fold (Group B; 2000.0 +/-671.8% increase in Penh) compared to controls (Group A; 445.7 +/-33.5% increase in Penh) (p = 0.016). The anti-IL 33 (Group C: 1579.4 +/-973.6% increase in Penh) and anti-Siglec-F (Group D: 930.4 +/-236.5%) groups demonstrated significantly reduced hyperreactivity (p = 0.029). Anti-IL-33/anti-Siglec-F therapy showed synergism towards neutrophil counts, IL-5 concentrations, bronchial infiltration, and hyperreactivity (p < 0.05). CONCLUSIONS: Combination treatment with anti-IL-33/anti-Siglec-F had more potent anti-allergic effects, reducing eosinophilic infiltration through their additive effects in a murine allergic asthma model. PMID- 26155159 TI - Exposure to hypergravity increases serum interleukin-5 and pulmonary infiltration in mice with allergic asthma. AB - OBJECTIVE: We evaluated the effect of acute hypergravity (HG) on the immune response in a murine model of allergic asthma. MATERIAL AND METHODS: Twenty-eight BALB/c mice were used. Group A (control group, n = 7) mice were sensitized and challenged with normal saline. Group B (control HG exposure group, n = 7) mice were sensitized, challenged with saline, and exposed to acute HG (+10 Gz) for 4 hours. Group C (asthma group, n = 7) mice were challenged with intraperitoneal and intranasal ovalbumin (OVA) to induce asthma. Group D (asthma HG exposure group, n = 7) mice were exposed to HG for 4 hours after the induction of asthma. We estimated the total and OVA-specific serum IgE, serum titers of various cytokines, and the number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid. Histopathology of the lung was also evaluated. RESULTS: The serum level of interleukin (IL)-5 was significantly higher in Group D (12.9 +/-4.9 pg/ml) compared to that in Group C (4.7 +/-6.5 pg/ml, p = 0.017). In BAL fluid, the number of neutrophils was significantly increased in Group D compared to Group C (p = 0.014). Group D demonstrated a higher infiltration of inflammatory cells (9973.8 +/-1642.7 cells/mm(2)) compared to Group C (7666.3 +/-586.5 cells/mm(2), p = 0.017). This tendency of increase in infiltration was not significant in non-asthmatic animals (Group A: 4488.8 +/ 176.1 cells/mm(2) vs. Group B: 4946.3 +/-513.7 cells/mm(2), p > 0.05). CONCLUSIONS: Acute HG exacerbated the allergic response by increasing serum IL-5 levels and promoting pulmonary infiltration of inflammatory cells. PMID- 26155160 TI - Zinc improves the immune function and the proliferation of lymphocytes in Cadmium treated rats. AB - The effects of Cadmium (Cd) exposure and the treatment with Zinc (Zn) on immune functions of splenocytes and cultured lymphocytes of rats were studied. The exposure of rats to Cd was at a dose of 2.2 mg/kg CdCl2, injected subcutaneously four times weekly for 2 months. Rats were supplemented with Zn (2.2 mg/kg ZnCl2, injected subcutaneously four times weekly for 2 months) one hour prior to Cd exposure. Spleens were removed and splenocytes were isolated and cultured. The proliferation capacity of lymphocytes and their homing to the spleen were studied. Ribonucleic acid (RNA) was extracted from stimulated lymphocytes in order to analyse gene expressions using RT-PCR. Accordingly, proliferation of lymphocytes was found to be suppressed in Cd-treated rats, both in vivo and in vitro. Zinc served to activate the proliferation of B and T lymphocytes in Cd treated rats both in vivo and in vitro. Antigen-activated lymphocytes showed that Cd impaired the mRNA expression of CD68, Ccl22 and CXCL10. Zinc was not found to restore mRNA expression of these genes to the normal levels. Zinc was found to decrease the MDA level with replenishment of activity of key antioxidant enzymes and proteins in Cd-pre-treated animals significantly. Moreover, the histopathological examination of spleen samples also agreed with the molecular, immunological and redox findings. Hence, Zn is able to restore the normal structure, redox status and immunity in Cd-induced damage in the rat model system. PMID- 26155161 TI - Inhibition of proliferation, migration and invasiveness of endothelial murine cells culture induced by resveratrol. AB - Angiogenesis is a multi-stage process of new vessel development which involves migration, proliferation and differentiation of endothelial cells. Pathological angiogenesis plays a crucial role in the pathomechanism of various ischemic, malignant and inflammatory disorders. Among eye diseases, macular degeneration (AMD) and proliferative diabetic retinopathy are a major public health issue as the most common causes of blindness. Since angiogenesis plays a crucial role in these conditions, there has been an increased interest in evaluating anti angiogenic agents in their treatment. The polyphenol resveratrol found in the skin of red grapes, red wine, peanuts and other natural sources, controls proliferation of the cells, induces differentiation and induces apoptosis in various malignant cell lines. Modulation of angiogenesis by this compound has been considered as a very exciting topic and subject of further investigations. The aim of our study was in vitro assessment of resveratrol's influence on proliferation, migration and invasion of an immortalized murine endothelial cell line from peripheral lymph node HEC clone a10. Resveratrol was shown to inhibit the proliferation of the endothelial cells in MTT (at 1, 10 and 50 uM) and AlamarBlue (at 50 uM) assays, and at a concentration of 50 uM significantly inhibited migration of endothelial cells. A concentration-dependent decrease in invasion potential of endothelial cells incubated with resveratrol 10 uM and 50 uM was detected. These promising in vitro results might encourage investigators to test efficacy and safety of resveratrol more extensively in the clinical practice, as a natural and safe anti-angiogenic agent. PMID- 26155162 TI - Distribution of the type I interferon in different organs of chicken digestive system. AB - OBJECTIVE: Distribution of the type I interferon in different organs of the chicken digestive system. MATERIAL AND METHODS: In order to obtain a certain length (274 bp) of a fragment, a pair of primers was designed according to the conserved nucleotide sequence of gallus IFNAR-1 (EU477527.1) fragment that was published by the GenBank. The fragment was cloned by pEASY-T1 and amplified by relative fluorescence quantitative PCR with SYBR Green I; according to the results, we made a standard curve. The experimental group took interferon orally, while the control group took equivalent physiological saline orally, then we used relative fluorescence quantitative PCR to detect the copies of the IFNAR-1 gene of the palate, tongue, esophagus, craw, glandular stomach, duodenum and rectum of the experimental group and control group. Copies of the IFNAR-1 gene of those organs were calculated by Ct value. Finally, all the chickens were infected with the Newcastle Disease Virus after 48 hours. RESULTS: The results showed that the IFNAR-1 gene had the most expression in the esophagus. In the experiment of interferon antiviral activity detection, the chickens which took interferon orally were healthier than the other group. CONCLUSIONS: It is confirmed that the interferon receptor did exist in the digestive organs. However, according to the physical and chemical properties of interferon, interferon is easily inactivated in the acid and alkali environment, by pepsin and trypsin, so the absorption site for interferon exists in organs above the craw, especially in the esophagus and tongue. PMID- 26155163 TI - Paeoniflorin reduced BLP-induced inflammatory response by inhibiting the NF kappaB signal transduction in pathway THP-1 cells. AB - Sepsis is a severe illness in which the bloodstream is overwhelmed by bacteria. Despite effective antibiotic treatment, the mortality of septic shock remains high. In this study, we examined a potential usage of paeoniflorin, anti inflammatory component for the treatment of sepsis. We established an inflammatory cell line by stimulating human THP-1 cell line with bacterial lipoprotein (BLP), which resulted in an activation of nuclear factor kappaB (NF kappaB) p65 dependent-signal pathway, and in consequence, an increase in tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 expression. With this model, we studied the effect of paeoniflorin on the expression of NF-kappaB and Toll-like receptor 2 (TLR2) mediated signal transduction. Our data indicated that paeoniflorin directly inhibited activation of NF-kappaB p65, thereby reduced the expression of TNF-alpha and IL-6 in the BLP stimulated THP-1 cells. Paeoniflorin was also found to inhibit IkappaB phosphorylation and degradation. However, no significant differences in TLR2 and myeloid differentiation factor 88 (MyD88) expression were observed; therefore, these signaling molecules may not have much anti-inflammatory effect in our cellular model. As such, our current study provided a molecular base for the potential use of paeoniflorin in therapeutic treatment of sepsis induced by bacterial lipoprotein. PMID- 26155164 TI - A novel peptide from TCTA protein inhibits proliferation of fibroblast-like synoviocytes of rheumatoid arthritis patients. AB - BACKGROUND: We have demonstrated that a peptide, which we named 'Peptide A', derived from the extracellular domain of T-cell leukemia translocation-associated gene (TCTA) protein, inhibited human osteoclastogenesis. OBJECTIVE: In the current study, we examined whether this peptide inhibits the proliferation of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) or not. MATERIAL AND METHODS: Fibroblast-like synoviocytes obtained from five RA patients were cultured in the absence or presence of 1, 5, 10 ug/ml of peptide. We used 29-mer scrambled peptide as a control. RESULTS: The peptide inhibited the proliferation of RA FLS dose-dependently. On the other hand, the scrambled peptide showed no inhibition. CONCLUSIONS: The peptide inhibits both human osteoclastogenesis and the proliferation of RA FLS. Thus, the peptide may be used for the therapy of both osteoporosis and synovitis of RA patients. This is the first report of the new peptide we discovered, which inhibits both osteoclastogenesis and synovitis. Thus, this new peptide could be a new drug for patients with both osteoporosis and RA. PMID- 26155165 TI - The influence of aqueous and hydro-alcoholic extracts of roots and rhizomes of Rhodiola kirilowii on the course of pregnancy in mice. AB - Plants belonging to the Rhodiola genus, originating from Asia, are traditionally used as tonic, adaptogen, antidepressant and anti-inflammatory drugs. These plants have also potent immunomodulatory properties and in some situations possibly could be used instead of standard antibiotic therapy (e.g. during pregnancy or lactation). The aim of our present study was to establish whether aqueous (RKW) or hydro-alcoholic (RKW-A) extracts from roots and rhizomes of Rhodiola kirilowii given to pregnant mice influence the course of pregnancy and the number of progeny. Performed HPLC analysis showed that the RKW-A extract had a generally higher concentration of all identified polyphenols. The highest differences were observed for (+)-catechin, p-coumaric acid and naringenin. Everyday addition of the RKW or RKW-A extract did not change the length of pregnancy. At the same time, both RKW and RKW-A extracts significantly increased the number of mated females without offspring but only in the RKW-A group we noticed a few neonatal deaths in the first 5 days after delivery. The results reported in the present study do not encourage to the use of R. kirilowii hydro alcoholic extracts supplementation during pregnancy and lactation, however the possibility of limited dietary intake of R. kirilowii water extract should be thoroughly examined. PMID- 26155166 TI - Genetic diversity and phylogenetic analysis of Tams1 of Theileria annulata isolates from three continents between 2000 and 2012. AB - Theileria annulata, which is part of the Theileria sergenti/Theileria buffeli/Theileria orientalis group, preferentially infects cattle and results in high mortality and morbidity in the Mediterranean, Middle East, and Central Asia. The polypeptide Tams1 is an immunodominant major merozoite piroplasm surface antigen of T. annulata that could be used as a marker for epidemiological studies and phylogenetic analysis. In the present study, a total of 155 Tams1 sequences were investigated for genetic diversity and phylogenetic relationships through phylogenetic analysis. Results showed that the Tams1 sequences were divided into two major groups and that distribution for some isolates also exhibited geographic specificity. As targeting polymorphic genes for parasite detection may result in underestimation of infection, polymerase chain reaction (PCR) assay using two different probes targeting tams-1 genes of these two groups can be more credible. In addition, the direction of the spread of the disease was discovered to be from the Mediterranean or the tropical zone to the Eurasian peninsula, Middle East, Southern Asia, and Africa, particularly for Group 2. A similar occurrence was also found between the Ms1 gene of Theileria lestoquardi and the Tams1 gene of T. annulata, which explains cross-immunogenicity to a certain extent. However, no potential glycosylation site in the Tams1 of T. annulata was found in this study, which illustrated that instead of N-glycosylation, other modifications have more significant effects on the immunogenicity of the Tams1 protein. PMID- 26155167 TI - The innate immunity of wild Eurasian beaver from Poland - present knowledge and the need for research. AB - For the first time we tried to examine the basic parameters of innate immunity in beavers for developing the new methods of prevention against infectious diseases in different reintroduction and translocation programmes in Poland. The aim of the present study was to determine the selected innate immunity parameters in Eurasian beavers living in natural conditions. The analyses of the results showed that the phagocytic ability (RBA) and potential killing activity (PKA) of blood phagocytes were higher in adult beavers compared to the young animals. The similar pattern was observed in proliferative response of blood lymphocytes stimulated by mitogens Concanavalin A (Con A) and lipopolysaccharides (LPS). The highest proliferative response in adult Eurasian beavers was observed. The ceruloplasmin activity in plasma was on similar levels in adult and young Eurasian beavers. The results of humoral mediated immunity showed that the lysozyme activity, total protein and gamma-globulin levels in serum were higher in adult beavers compared to the young beavers. The results of this preliminary study are important in comparative and clinical immunology. PMID- 26155168 TI - Cellular immunity profile in children with congenital heart disease and bronchopneumonia: evaluation of lymphocyte subsets and regulatory T cells. AB - Children with congenital heart disease (CHD) have a predisposition to suffer from respiratory tract infections, such as bronchopneumonia (BP). In this study we investigated the characterization of lymphocyte subsets and regulatory T cells (Tregs) in these children. The frequencies of lymphocyte subsets and regulatory T cells were detected in peripheral blood of 400 children patients [100 with BP only, 100 with BP and CHD (BPCHD), 100 with BP and heart failure (BPHF), 100 healthy volunteers] by using three-color flow cytometry. In BPHF and BPCHD groups, lymphocyte subsets characterization of patients was analogous, with lower levels of CD3+, CD3+CD4+, CD3+CD8+, and CD4+/CD8+ ratio but higher levels of CD19+ and CD3-CD16+CD56+ in comparison to BP patients. The differences of the frequencies of CD4+CD25+CD127- T-cells in the four groups were not statistically significant. It was concluded that the cellular immunity function of children with CHD was vulnerable to being damaged after having suffered from BP when compared with the children without CHD, which might be associated with blood circulation difficulties in the majority of children with CHD. PMID- 26155169 TI - Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis. AB - INTRODUCTION: It has been known that vitamin D has some immunomodulatory effects and in autoimmune thyroid diseases, vitamin D deficiency was more prevalent. In this study, our aim was to investigate the relationship between thyroid autoantibodies and vitamin D. MATERIAL AND METHODS: Group 1 and 2 consisted of 254 and 27 newly diagnosed Hashimoto's thyroiditis (HT) and Graves' disease (GD) cases, respectively; age-matched 124 healthy subjects were enrolled as controls (group 3). All subjects (n = 405) were evaluated for 25OHD and thyroid autoantibody [anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti tg)] levels. RESULTS: Group 2 and group 1 patients had lower 25OHD levels than group 3 subjects 14.9 +/-8.6 ng/ml, 19.4 +/-10.1 ng/ml and 22.5 +/-15.4 ng/ml, respectively (p < 0.001). Serum 25OHD levels inversely correlated with anti-tg (r = -0.136, p = 0.025), anti-TPO (r = -0.176, p = 0.003) and parathormone (PTH) (r = -0.240, p < 0.001). Group 2 patients had higher anti-tg and anti-TPO levels than group 1 and 3 (p < 0.001). CONCLUSIONS: In this study, we found that patients with autoimmune thyroid disease (AITD) present with lower vitamin D levels and GD patients have higher prevalence. Since we found an inverse correlation between vitamin D levels and thyroid antibody levels, we may suggest that vitamin D deficiency is one of the potential factors in pathogenesis of autoimmune thyroid disorders. PMID- 26155170 TI - Gene expression disorders of innate antibacterial signaling pathway in pancreatic cancer patients: implications for leukocyte dysfunction and tumor progression. AB - The study was carried out to investigate changes in gene expression of innate antibacterial signaling pathways in patients with pancreatic cancer. Expression of the following genes was measured in peripheral blood leukocytes of 55 patients with pancreatic adenocarcinoma using real-time polymerase chain reaction (RT PCR): TLR4, NOD1, MyD88, TRAF6 and HMGB1. The levels of expression of TLR4, NOD1 and TRAF6 genes were significantly elevated (p = 0.007; p = 0.001 and p = 0.01, respectively), while MyD88 expression was markedly reduced (p = 0.0002), as compared to controls. Expression of TLR4 and NOD1 exceeded the normal level more than 3.5-fold and there was a significant correlation found between the expression of these genes (r = 0.558, p < 0.001). TLR4, NOD1 and MyD88 genes were expressed at a similar level both before and after surgery. No significant changes in the expression of HMGB1 gene were observed. The results of the study clearly indicate abnormal expression of genes belonging to innate antibacterial signaling pathways in peripheral blood leukocytes of patients with pancreatic cancer, which may lead to leukocyte dysfunction. Overexpression of TLR4, NOD1 and TRAF6 genes, and decreased MyD88 gene expression may contribute to chronic inflammation and tumor progression by up-regulation of the innate antibacterial response. The parameters tested are useful for monitoring innate immunity gene disorders and pancreatic cancer progression. PMID- 26155171 TI - Receptor activator of NF-kappaB ligand (RANKL) and CD 31 expressions in chronic periodontitis patients before and after surgery. AB - AIM OF THE STUDY: The present study investigated the hypothesis that upregulation of receptor activator of NF-kappaB ligand (RANKL) expression may be associated with upregulation of endothelial cell activitiy, which is common for periods of periodontal bone loss in chronic periodontitis. MATERIAL AND METHODS: RANKL expression of activated cells in soft tissue biopsies with CD 31 activity and the presence of RANKL and osteoprotegerin (OPG) in gingival crevicular fluid (GCF) were assessed in chronic periodontitis patients. Biopsies from 17 patients and 10 healthy subjects were immunohistochemically analyzed. Clinical measurements [plaque index (PI), the gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL) and gingival bleeding index (GBI)] and GCF samples were obtained before and after periodontal therapy. RESULTS: CD31 staining did not support the assumption that endothelium-like cells were predominantly associated with RANKL expression. CONCLUSIONS: RANKL-positive cells were widely distributed in periodontitis patients giving only partial support to the hypothesis that RANKL expression is restricted to T- and B-cell activation. PMID- 26155172 TI - Host response, malnutrition and oral diseases. Part 1. AB - Effective defense response of the body requires the proper nutritional and metabolic preparation and adequate energy expenditure. Every pathological process with coexisting malnutrition is subject to an increased risk of failure and complications in medical treatment, which is a serious threat to human health and life. Malnutrition, particularly protein-calorie malnutrition, is characterized by a decrease in resistance, particularly involving cellular immune deficiency, which in turn causes a significant decrease in resistance to infections. Inflammation is the price that the organism has to pay for the effective antimicrobial defense. Therefore, uncontrolled changes may occur in the immune system in nutrition disorders, especially in a significant protein-calorie malnutrition, which in turn prevents the correct response to microbial infection, including bacterial infection, which occurs in the course of periodontitis or untreated caries disease. Research determining the relationship between the clinical state of oral health, selected immune parameters and indicators of nutritional status of the organism, is an alternative to other attempts undertaken to reduce these risks. PMID- 26155173 TI - Host response, malnutrition and oral diseases. Part 2. AB - Acute phase proteins enhance antioxidant defenses; they are involved in the activation of complement components, opsonization and increase in platelet aggregation as well as inhibition of the respiratory burst in the course of inflammation. Malnutrition plays an important role in the course of response of acute phase proteins. The role of nutrients as antioxidants or as key components of antioxidant enzymes is commonly known. In the course of various inflammatory states, including oral diseases, disorders are observed in caloric requirements of the organism and the requirements for specific amino acids. Numerous experimental studies in animals have also confirmed the relationship between protein- calorie malnutrition and hypofunction of the salivary glands. Studies in children with malnutrition syndrome showed a significantly lower volume of saliva compared to properly nourished children. Depleted nutritional reserves due to long-term chronic malnutrition cause a significant reduction in resistance, progressive damage to the oral mucosa, and reduce resistance to colonization and invasion of pathogenic microorganisms. PMID- 26155174 TI - Immunological aspects of chronic venous disease pathogenesis. AB - Chronic venous disease (CVD) is a very common health problem concerning up to 1/3 of the society. Although venous hypertension and valvular incompetence have been long known to be crucial for development of the illness, its exact aetiology remains unclear. Recent findings indicate that inflammatory processes may be crucial for development of incompetent valves and vein wall remodelling. One of the most interesting theories describes "leucocyte trapping" as the mechanism responsible for elevated vein wall permeability and oxidative stress in the veins. At the same time, the cytokine profile of the blood in incompetent veins has not been thoroughly examined. Popular anti-inflammatory drugs relieve some symptoms but do not have much proved effects in prevention and treatment. We intend to summarize the existing knowledge of the immunological aspects of CVD in order to emphasize its importance for understanding the aetiology of this illness. We also wish to indicate some aspects that remain to be studied in more detail. PMID- 26155175 TI - The immune response to surgery and infection. AB - Surgical trauma affects both the innate and acquired immunity. The severity of immune disorders is proportional to the extent of surgical trauma and depends on a number of factors, including primarily the basic disease requiring surgical treatment (e.g. cancer), often coexisting infections and impaired nutritional status. Disorder of the immune response following surgical trauma may predispose to septic complications burdened with the highest mortality rate. Extensive surgery in cancer patients is associated with simultaneous activation of pro- and anti-inflammatory processes defined as SIRS (systemic inflammatory immune response) and CARS (compensatory anti-inflammatory immune response). However, it is generally believed that major surgical trauma is accompanied by sustained postoperative immunosuppression, which is particularly important in patients operated on for cancer, since the suppression of the immune system promotes not only septic complications, but also proliferation and tumor metastasis. This paper reviews the main features of immune response to surgical trauma and possibilities of its regulation. PMID- 26155176 TI - Synergistic anticancer activity of biologicals from green and black tea on DU 145 human prostate cancer cells. AB - There is considerable interest in the potential of botanicals in preventing and/or alleviating chronic ailments. Among the most studied botanicals are compounds present in green and black teas. Nontoxic tea polyphenols are potent antioxidants, and they also modulate several signalling pathways and inhibit proteins such as MMP-9 or protein plasminogen activator system, making them very attractive potential therapeutics. One criticism of the prophylactic or therapeutic use of green or black tea polyphenols was presumably the poor bioavailability of these chemicals when ingested. However, studies have shown that epigallocatechin-3-gallate (EGCG) and theaflavin (TF) can be detected in the small and large intestine, liver, and prostate of experimental animals after consumption of tea extracts. In particular, a study was carried out on 20 men scheduled for prostatectomy, who were assigned to consume teas for five days before surgery. Tea polyphenols were detected in the prostate. This fact contradicts the common misconception of poor bioavailability of TF and EGCG and makes feasible the application of green or black tea polyphenols as prophylactic and therapeutic agents. Theaflavins and catechins seem to act on cancer cells largely through different pathways, so utilisation of both could offer synergistic anticancer effects, but so far no work has been done on the cumulative effects of EGCG and TF on prostate cancer. Therefore, in this study we have investigated if EGCG in combination with TF can reduce the rate of prostate cancer growth, and we have observed greater cell death compared to application of either TF or EGCG alone. PMID- 26155177 TI - Influence of beta-glucan Leiber((r))Beta-S on selected innate immunity parameters of European eel (Anguilla anguilla) in an intensive farming system. AB - Nutritional support plays an important role in promoting high cellular and humoral innate immunity activity and in preventing outbreaks of disease. The effects of beta-glucan Leiber((r))Beta-S dietary supplementation on selected nonspecific immune parameters in juvenile European eel (Anguilla anguilla) in an intensive culture system were studied. The fish were fed commercial pellets containing either 0 (control group) or 200 mg Leiber((r))Beta-S kg-1 of feed (glucan-fed group). After four and eight weeks of feeding, the levels of the following immunological parameters were measured: phagocyte respiratory burst activity, phagocyte potential killing activity, lymphocyte proliferation stimulated by concanavaline A or lipopolysaccharide, serum lysozyme activity, and total immunoglobulin (Ig) serum levels. After four and eight weeks of feeding 200 mg Leiber((r))Beta-S kg feed-1 the levels of all immune parameters were statistically significantly higher (p < 0.05) in the glucan-treated group than in the control group. After eight weeks of feeding the fish 200 mg Leiber((r))Beta-S kg feed-1 and after an additional eight weeks in ponds, the levels of all immune parameters, excluding lymphocyte proliferation stimulated by concanavaline A, were statistically significantly higher (p < 0.05) in the glucan-fed group than in the control group. These data suggest that feeding juvenile eel Leiber((r))Beta-S for four and eight weeks might improve innate immunity. PMID- 26155178 TI - The effects of EGb761 on lipopolysaccharide-induced depressive-like behaviour in C57BL/6J mice. AB - There is an increasing body of evidence for the involvement of inflammation and brain-derived neurotrophic factor (BDNF) in depression. Ginkgo extract EGb761 possesses anti-inflammatory, anti-oxidative, anti-arteriosclerosis, and neuroprotective activities. But the effect of EGb761 on lipopolysaccharide (LPS) induced depressive-like behaviours has not been investigated. The present study mainly aimed to examine the antidepressant-like activities of Ginkgo extract EGb761 in mice after lipopolysaccharide administration. C57BL/6J male mice were pretreated with EGb761 or vehicle for 10 days. Then, a single dose of lipopolysaccharide was intraperitoneally administrated to mice to induce depressive-like behaviour. Forced swim test (FST), tail suspension test (TST), and sucrose preference test were performed to evaluate the depressive-like behaviours of the mice. Locomotor activity was examined by open field test. Levels of brain-derived neurotrophic factor, TNF-alpha, IL-1beta, IL-6, IL-17A, and IL-10 in hippocampus tissue homogenate were measured using ELISA kits. We found that LPS administration induced significant depressive-like behaviours, higher levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, IL-6, and IL-17A, but lower levels of BDNF and IL-10 in hippocampus tissue homogenate of the mice from the vehicle group compared to the control mice. Pretreatment with middle dose (100 mg/kg/day) and high dose (150 mg/kg/day) of EGb761 significantly attenuated depressive-like behaviours without affecting spontaneous locomotor activity, and inhibited the changes of hippocampal cytokines and BDNF induced by LPS administration. We conclude that EGb761 has antidepressant-like activities in mice with LPS-induced depressive-like behaviours. PMID- 26155179 TI - Comparison between magnetic activated cell sorted monocytes and monocyte adherence techniques for in vitro generation of immature dendritic cells: an Egyptian trial. AB - INTRODUCTION: Dendritic cells (DCs) are the most efficient antigen presenting cells, which are considered a central component of the immune system for their extraordinary capacity to initiate and modulate the immune responses elicited upon recognition of infectious agents. This has made them a major focus of interest in the conception of immunotherapeutic vaccine strategies. AIM OF THE STUDY: To standardise a protocol for in vitro differentiation of human peripheral blood monocytes into immature DCs (iDCs) upon treatment with specific growth factors and to compare two monocyte isolation methods including magnetic activated cell sorted (MACS) monocytes by CD14(+) immuno-magnetic beads and monocytes separated by adherence. MATERIAL AND METHODS: Immature DCs were generated from monocytes of human peripheral blood in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 after in vitro culture for seven days. Cultured cells were stained with surface markers of iDCs: FITC-anti-CD14, PE-anti-CD11c, PE-anti-CD1a, PE-Cy5-anti-HLA-DR, and PE anti-CD83 for flow cytometry analysis. RESULTS: We found that the viability of MACS-DCs was higher than DCs derived from monocytes separated by adherence (median 50 and interquartile range 45-50 vs. 25 and 10-30, respectively; p < 0.001). Flow cytometry analysis revealed that the median interquartile percentages of MACS-DCs expressing CD14(-) was significantly higher compared to the DCs derived from monocytes separated by adherence (median 80.2 and interquartile range 77.7-80.7 vs. 40.2 and 30.4-40.6, respectively; p < 0.001). However, MACS-DCs expressed the same levels of CD11c, CD1a, and HLA-DR as well as CD83 compared to the DCs derived from monocytes separated by adherence with p value > 0.05. CONCLUSIONS: Both positively selected monocytes and monocytes separated by adherence procedure gave the same results as regards cell surface marker expression, although the DCs purity and viability using MACS separated monocytes were better. PMID- 26155180 TI - The production of cross-reactive autoantibodies that bind to bovine serum albumin in mice administered reducing sugars by subcutaneous injection. AB - INTRODUCTION: In a previous study, we identified the formation of cross-reactive autoantibodies that bound to bovine serum albumin (BSA) in a D-galactose-induced aging mouse model. AIM OF THE STUDY: In this study, we investigated the effect of other reducing sugars (namely, glucose and fructose) on the formation of autoantibodies. The effects of concentration and route of administration on the formation of autoantibodies were examined in detail. MATERIAL AND METHODS: Three concentrations (100, 500, and 1,000 mg/kg) of reducing sugars were tested. The effects of different routes of administration (subcutaneous, oral, and intraperitoneal) on the formation of autoantibodies were also analysed. The immunoreactivities of serum samples from mice treated with reducing sugars were analysed by an enzyme-linked immunosorbent assay (ELISA) using BSA or mouse serum albumin antigens (MSA). RESULTS: Repeated subcutaneous administration of all reducing sugars lead to autoantibody formation in a concentration-dependent manner. However, these autoantibodies did not cross-react with MSA, and simultaneous treatment of aminoguanidine with reducing sugars did not show any inhibitory effects on the formation of autoantibodies. No autoantibodies were detected after oral or intraperitoneal administration of reducing sugars. Immunohistochemistry data showed that the target antigen(s) of the autoantibodies were present only in the skin tissue of mice treated with reducing sugars. CONCLUSIONS: Our results show that administration of reducing sugars by subcutaneous injection leads to the formation of autoantibodies that cross-react with BSA; the formation and target antigen(s) of the autoantibodies may originate from within the skin tissue treated with the reducing sugars. PMID- 26155181 TI - Proteomic and immunological identification of two new allergens from silkworm (Bombyx mori L.) pupae. AB - This study explored food allergy caused by eating silkworm (Bombyx mori L.) pupae, a traditionally accepted food and animal feed in East and Southeast Asia, and identified two new allergens by proteomic and immunological methods. Proteins isolated from silkworm pupae were separated by two-dimensional gel electrophoresis (2-DE); pooled sera from patients allergic to silkworm pupa proteins were used to detect immunoglobulin E (IgE)-binding proteins by western blotting, and allergens specific for silkworm pupa consumption-caused allergy were visualised with the ECL reagents. The selected allergen proteins were further identified by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) analysis. Finally, chitinase and paramyosin were identified as silkworm pupa proteins showing strong immunoglobulin (IgE)-binding reaction. Analysis of the sequence homology of the two proteins using the AllergenOnline database indicated that chitinase and paramyosin shared 24.8% and 62.8% sequence homology with known allergens Der f 18 (Dermatophagoides farinae) and Der p 11 (Dermatophagoides pteronyssinus), respectively. Our results shed light on the understanding and treatment of silkworm pupa allergy. PMID- 26155182 TI - Rhamnetin attenuates cognitive deficit and inhibits hippocampal inflammatory response and oxidative stress in rats with traumatic brain injury. AB - Activation of the immune system in the central nervous system and oxidative stress play important roles in traumatic brain injury (TBI)-induced cognitive impairment. Rhamnetin possesses anti-inflammatory and anti-oxidative properties. This study aimed to detect the possible effects of rhamnetin on cognitive deficit, hippocampal inflammatory factors, and oxidative stress in rats with TBI. In this study, we established the traumatic brain injury model in rats. Rats respectively received vehicle saline or rhamnetin for 21 days. Cognitive functions were evaluated by assessing the acquisition of spatial learning and memory retention in Morris Water Maze test from day 15 to 19 post TBI. Levels of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor a (TNF-a), IL-10, and nuclear factor kappaB (NF-kappaB) in hippocampal homogenate were measured using ELISA. Oxidative stress was analysed by investigating the activities of MDA, H2O2, SOD, and GSH-Px. We found that rhamnetin significantly improved cognitive impairment in rats with TBI, and inhibited the inflammatory response and oxidative stress in the hippocampus. The results suggested that rhamnetin could enhance the recovery of cognitive deficits induced by TBI, and that its mechanism might be associated with the inhibition of inflammation and oxidative stress in the hippocampus. PMID- 26155183 TI - Necrosis and apoptosis in Trichinella spiralis-mediated tumour reduction. AB - It is known that infection with different pathogens, including helminths, can alter the progression of malignant or other diseases. We studied the effect of chronic Trichinella spiralis infection or muscle larvae excretory-secretory (ES L1) antigens on the malignant tumour growth in the mouse melanoma model system in vivo and in vitro. Our results confirmed that chronic infection with T. spiralis possesses the capacity to slow down the progression of tumour growth, resulting in an impressive reduction in tumour size. We found that the phenomenon could, at least partially, be related to a lower level of tumour necrosis compared to necrosis present in control animals with progressive malignancy course. An increased apoptotic potential among the low percentage of cells within the total tumour cell number in vivo was also observed. ES L1 antigen, as a parasitic product that is released during the chronic phase of infection, reduced the survival and slightly, but significantly increased the apoptosis level of melanoma cells in vitro. Our results imply that powerful Trichinella anti malignance capacity does not rely only on necrosis and apoptosis but other mechanisms through which infection or parasite products manipulate the tumor establishment and expansion should be considered. PMID- 26155184 TI - In vitro interferon gamma improves the oxidative burst activity of neutrophils in patients with chronic granulomatous disease with a subtype of gp91phox deficiency. AB - AIM OF THIS STUDY: Chronic granulomatous disease (CGD) is a genetically heterogeneous primary immunodeficiency caused by a defect in phagocyte production of oxygen metabolites, and resulting in infections produced by catalase-positive microorganisms and fungi. Interferon gamma (IFN-gamma) has a multitude of effects on the immune system. Although preliminary studies with CGD patients on treatment with IFN-gamma showed that it enhanced phagocytosis and superoxide production, ongoing studies did not reveal a significant increase of this function. Here we investigated the oxidative capacity of phagocytes in different subtypes of CGD patients on treatment with IFN-gamma in vitro. MATERIAL AND METHODS: Fifty-seven patients with CGD from 14 immunology centres were enrolled to our multi-centre study. Twenty-one patients were studied as controls. Oxidative burst assay with dihydrorhodamine 123 (DHR) was used and the stimulation index (SI) was calculated with respect to CGD subtypes in both neutrophils and monocytes before, and then one and 24 hours after adding IFN-gamma. RESULTS: Upon comparison of the SIs of the patients' neutrophils before in vitro IFN-gamma at hour 0, and after adding IFN-gamma at hour 1 and 24 were compared, and the differences were determined between hours 0-24 and hours 1-24. This difference was especially apparent between hours 1-24. In CGD subtypes, particularly in gp91phox subtype, it was seen that, following in vitro IFN-gamma, SIs of neutrophils began to increase after hour 1, and that increase became more apparent at hour 24. CONCLUSIONS: Our study showed that IFN-gamma treatment may increase the oxidative bursting activity by increasing the superoxide production in neutrophils, particularly in gp91phox subtype. PMID- 26155185 TI - Mucosal interleukin-21 mRNA expression level is high in patients with Helicobacter pylori and is associated with the severity of gastritis. AB - Helicobacter pylori (H. pylori) infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells. Different clinical forms of the infection may reflect distinctive patterns of cytokine expression. Interleukin (IL)-17, IL-21, IL-22, and IL-23 have been reported to be involved in H. pylori-induced gastric mucosal inflammation, but the details and relationship to different patterns of inflammation and virulence factors remain unclear. The present study was launched to analyse IL-6 expression in H. pylori-infected and uninfected gastric patients and to investigate its correlation with chronic gastritis among H. pylori-infected patients. Total RNA was extracted from the gastric antrum biopsies of 48 H. pylori-infected patients and 38 H. pylori uninfected patients. Mucosal IL-21 mRNA expression level in H. pylori-infected and uninfected gastric biopsy was determined by real-time PCR. The presence of vacA (vacuolating cytotoxin A) and cagA (cytotoxin associated gene A) virulence factors were evaluated using PCR. Interleukin-21 mRNA expression was significantly high in biopsies of H. pylori-infected patients compared to H. pylori uninfected patients, and the mucosal IL-21 mRNA level was positively correlated with the grade of chronic inflammation. There was no association between virulence factors and IL-21 mRNA expression. We believe that IL-21 might be involved in the pathogenesis of H. pylori and might be an index of the severity of chronic gastritis. PMID- 26155186 TI - Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms. AB - In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1beta 31 T/C, IL-6 -174 G/C, tumor necrosis factor alpha (TNF-alpha) -308 G/A, and interferon gamma (IFN-gamma) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5' nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1beta, IL-6, TNF-alpha, and IFN-gamma were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1beta -31C, IL-6 -174G, TNF alpha -308G, and IFN-gamma +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns. PMID- 26155187 TI - Prohibitin as a novel autoantigen in rheumatoid arthritis. AB - THE AIM OF THIS STUDY: The aim of this study was to verify whether prohibitin is a novel autoantigen in rheumatoid arthritis. MATERIAL AND METHODS: First, recombinant human prohibitin (rhPHB) protein was cloned, expressed, and purified. Then the anti-prohibitin autoantibodies were detected by western blotting by using rhPHB protein to incubate sera from patients with rheumatoid arthritis (RA). Next, immunoprecipitation was employed to further illustrate whether anti prohibitin antibodies exist in RA patients. And finally, autoantibodies against the rhPHB protein were investigated using a homemade ELISA kit through the assessment of 258 real clinical samples. RESULTS: It was revealed that anti prohibitin antibodies existed in the sera of patients with RA. Reactivity of serum IgG against rhPHB was detected in 26 of 86 RA patients (30.3%), 7 of 86 systemic lupus erythematosus (SLE) patients (8.1%), and 1 of 86 apparently healthy donors (HC) (1.2%). CONCLUSIONS: Prohibitin was proved to be a novel autoantigen and the corresponding anti-prohibitin autoantibodies were present in the RA patients' blood circulation. PMID- 26155188 TI - Thrombocytopenia in common variable immunodeficiency patients - clinical course, management, and effect of immunoglobulins. AB - Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections. High prevalence of autoimmunity is characteristic for CVID, most commonly: thrombocytopaenia and neutropaenia, celiac disease, and systemic autoimmune diseases. The study included seven children diagnosed with CVID and treated with immunoglobulin substitution from 2 to 12 years. Thrombocytopenia was diagnosed prior to CVID in four children, developed during immunoglobulin substitution in three children. In one boy with CVID and thrombocytopaenia, haemolytic anaemia occurred, so a diagnosis of Evans syndrome was established. Therapy of thrombocytopaenia previous to CVID included steroids and/or immunoglobulins in high dose, and azathioprine. In children with CVID on regular immunoglobulin substitution, episodes of acute thrombocytopaenia were associated with infections and were treated with high doses of immunoglobulins and steroids. In two patients only chronic thrombocytopaenia was noted. Splenectomy was necessary in one patient because of severe course of thrombocytopaenia. The results of the study indicated a supportive role of regular immunoglobulin substitution in patients with CVID and chronic thrombocytopaenia. However, regular substitution of immunoglobulins in CVID patients did not prevent the occurrence of autoimmune thrombocytopaenia episodes or exacerbations of chronic form. In episodes of acute thrombocytopaenia or exacerbations of chronic thrombocytopaenia, infusions of immunoglobulins in high dose are effective, despite previous regular substitution in the replacing dose. PMID- 26155189 TI - Pneumocystis pneumonia in children - the relevance of chemoprophylaxis in different groups of immunocompromised and immunocompetent paediatric patients. AB - INTRODUCTION: Pneumocystis jirovecii is an opportunistic pathogen causing pneumocystis pneumonia (PCP), a life-threatening infection, in immunocompromised patients. In this study, retrospective analysis of the presence of P. jirovecii DNA in different samples collected from children with suspected PCP was carried out. MATERIAL AND METHODS: Three hundred and six specimens [152 bronchoalveolar lavage (BAL) specimens, 80 blood specimens, 18 bronchial secretions (BS), 34 induced sputum samples, 10 endotracheal aspirates (ETA), and 12 other type samples] obtained from patients with suspected PCP were examined by real-time PCR. RESULTS: Forty (13.1%) patients were positive for P. jirovecii: 4 (7.7%) patients with malignancies, 3 (6.8%) transplant recipients, 15 (23.1%) other immunocompromised patients, and 18 (12.4%) immunocompetent patients. Pneumocystis jirovecii DNA was detected in 20.4% of BAL specimens, 11.1% of BS samples, 10% of ETA sample, 8.8% of induced sputum samples, and in 3.7% of blood samples. Comparing the frequency of the presence of P. jirovecii DNA between the group of children treated with PCP chemoprophylaxis (malignancy patients and transplant recipients) and a group of children not receiving this prophylaxis (other immunocompromised and immunocompetent children), we found that the occurrence of PCP was twice as high in the latter group of children (7.3% and 15.7%, respectively). CONCLUSIONS: Respiratory samples, such as BS, BAL, or ETA specimens, are the material of choice for the diagnosis of PCP. Due to high incidence of PCP in certain groups of immunocompetent and immunocompromised patients, besides cancer patients and transplant recipients, consideration of PCP prophylaxis is required in these groups as well. PMID- 26155190 TI - Pro-inflammatory cytokines for evaluation of inflammatory status in endometriosis. AB - THE AIM OF THE STUDY: The aim of the study was to investigate the serum pro inflammatory cytokine profile in patients with diagnosed endometriosis. MATERIAL AND METHODS: The study included 160 women, who were divided in two study groups (Group I - endometriosis; Group 2 - healthy). We evaluated the serum levels of interleukin (IL)-1beta, IL-5, IL-6, IL-7, and IL-12, and of tumour necrosis factor alpha (TNF-alpha) with the use of Human Multiplex Cytokine Panels. RESULTS: The serum level of IL-1beta, IL-6, and TNF-alpha is significantly higher in women with endometriosis compared to women free of disease, from the control group (mean 10.777, 183.027, and 131.326, respectively, compared to 3.039, 70.043, and 75.285, respectively; p = 0.002, p < 0.001, and p = 0.015, respectively). No significant differences in the serum levels of IL-5 and IL-12 were observed between the studied groups, and IL-7 had a very low detection rate. CONCLUSIONS: Women with endometriosis have elevated levels of key pro inflammatory cytokines, i.e. IL-1beta, IL-6, and TNF-alpha. At the same time, IL 1beta and IL-6 could be used as predictors for endometriosis. PMID- 26155191 TI - The role of dendritic cells and regulatory T cells in the pathogenesis of morphea. AB - Morphea is one of diseases characterised by fibrosis of the skin and subcutaneous tissue. It is a chronic disease that does not shorten the life of the patient, yet significantly affects its quality. The group of factors responsible for its pathogenesis is thought to include disturbed functioning of endothelial cells as well as immune disturbances leading to chronic inflammatory conditions, accompanied by increased production of collagen and of other extracellular matrix components. Dendritic cells (DC) are a type of professional antigen-presenting cells and can be found in almost all body tissues. Individual investigations have demonstrated high numbers of plasmacytoid DC (pDC) in morphoeic skin lesions, within deeper dermal layers, around blood vessels, and around collagen fibres in subcutaneous tissue. It appears that DC has a more pronounced role in the development of inflammation and T cell activation in morphea, as compared to systemic sclerosis (SSc). Regulatory T (Treg) cells represent a subpopulation of T cells with immunosuppressive properties. Recent studies have drawn attention to the important role played by Treg in the process of autoimmunisation. Just a few studies have demonstrated a decrease in the number and activity of Treg in patients with SSc, and only such studies involve morphea. This article reviews recent studies on the role of DC and regulatory T cells in the pathogenesis of morphea. Moreover, mechanisms of phototherapy and potential therapeutic targets in the treatment of morphea are discussed in this context. PMID- 26155192 TI - Fabricated or induced illness in the oral cavity in children. A systematic review and personal experience. AB - INTRODUCTION: Munchausen syndrome by proxy (MSBP) describes a pattern in which a caregiver induces a disease in a child. The symptoms may manifest in the oral cavity. MATERIAL AND METHODS: PubMed was researched for articles between 1990 2014, presenting manifestations of MSPB, following PRISMA 2009 guidelines, and an in-house case of MSBP with oral manifestations was presented. REVIEW: Among 66 articles presenting MSBP symptoms, four included descriptions of oral lesions in five children. They included: tooth loss, ulcerations and ulcers on oral mucosa, scars due to old, healed lesions, bleeding, black tongue, polysialia, and discolouration and swelling in the lips. Munchausen syndrome by proxy with participation of the mother was diagnosed in four cases. CASE: A 13-year-old girl was hospitalised because of a non-healing ulcer of the septum, loose and lost mandibular teeth, skin lesions, and suspected immunodeficiency. She had been hospitalised numerous times at other facilities. Consultations and diagnostic tests did not confirm an organic disease. The patient and her mother agreed to undergo all examinations, and some symptoms 'went away' during the examinations. The behaviour of the patient and her mother during hospital stays, ambulatory care, and the psychiatric observations all pointed towards MPSB. They refused further treatment at the present facility. CONCLUSIONS: A dentist should take into account the potential 'fabrication' of symptoms in a child by the latter or by a caregiver. Consultations with a paediatrician or psychiatrist enable a diagnosis and treatment. PMID- 26155193 TI - Coexistence of hereditary angioedema in a case of familial Mediterranean fever with partial response to colchicine. AB - Hereditary angioedema (HAE) is a very rare and potentially life-threatening genetic disease characterised by episodes of edema in various parts of the body, including the extremities, face, and airway. The disease is usually associated with attacks of abdominal pain. On the other hand, familial Mediterranean fever (FMF) is an inherited condition characterised by recurrent episodes of painful inflammation in the abdomen, chest, or joints. In this report, we present a child with FMF and undiagnosed HAE, which made him a partial responder to colchicine treatment. Consequently, HAE must be considered in differential diagnosis of cases in which a partial response is obtained from FMF treatment, particularly in countries where FMF is frequently encountered, because early diagnosis of HAE can facilitate prevention of life-threatening complications, such as upper airway obstruction. To our knowledge, our patient is the first patient reported in the literature with the diagnosis of HAE and FMF together. PMID- 26155194 TI - Invasive pulmonary aspergillosis accompanied by soft tissue lesions during treatment of a patient with hyperthyroidism: a case report. AB - Invasive pulmonary aspergillosis (IPA) is difficult to diagnose because it requires histopathology and tissue culture, as well as due to its rapid progression. Invasive pulmonary aspergillosis is the primary cause of pulmonary mycosis in China, which can occur in patients with neutrophil deficiency, leukaemia or lymphoma, malignant tumours, or chronic obstructive pulmonary disease with long-term corticosteroid use or bacterial exacerbations. Such fungal infections can lead to disseminated disease and death within weeks, and the mortality rate for untreated invasive aspergillosis is high. Therefore, increased awareness of invasive aspergillosis in non-traditional hosts is warranted due to the high mortality rate experienced by patients with this disease. Invasive pulmonary aspergillosis has become a principal cause of life-threatening infections in immunocompromised patients. Invasive aspergillosis frequently involves the lung parenchyma and is infrequently accompanied by soft tissue lesions. We present an unusual case of a patient with agranulocytosis that was caused by methimazole that was given to control his hyperthyroidism, and IPA that was accompanied by unusual maxillofacial soft tissue swelling that required treatment with voriconazole. Upon follow-up 11 months later, a chest computed tomography scan (CT) revealed that most lesions had been completely absorbed. Moreover, his maxillofacial ulcers had become encrusted, and the soft tissue swelling had subsided. PMID- 26155195 TI - Successful treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disease with central nervous system involvement following allogeneic haematopoietic stem cell transplantation - a case study. AB - Post-transplant lymphoproliferative disease (PTLD) is a rare but severe form of Epstein-Barr virus (EBV)-driven complication that develops in patients after haematopoietic stem cell transplantation. In rare cases it manifests as primary central nervous system (CNS) involvement, which is thought to be the most unfavourable localisation with respect to outcome. Disease confined to the CNS is much more challenging than systemic PTLD, and one of the contributing factors is the limited drug penetration across the blood-brain barrier. We describe the case of a 29-year-old woman who was successfully treated for PTLD with CNS involvement. The patient was diagnosed with T-cell lymphoblastic lymphoma and underwent the procedure of haematopoietic stem cell transplantation from an unrelated donor. Two months after transplantation she manifested severe headache and progressive mental deterioration accompanied by enlargement of the lymph nodes. Magnetic resonance imaging (MRI) scan revealed segmental, asymmetrical thickening of the meninges. Based on the clinical picture and the laboratory findings diagnosis of PTLD was made. The patient was effectively treated with reduction of immunosuppressive therapy and intravenous rituximab. Initially started intrathecal chemotherapy was stopped due to iatrogenic complications. We conclude that in this case the involvement of meninges in the course of the lymphoproliferative process might have compromised the blood-brain barrier. This factor probably improved rituximab's penetration to CNS, contributing to our patient's recovery. PMID- 26155196 TI - Prevalence of perennial severe allergic asthma in Italy and effectiveness of omalizumab in its management: PROXIMA - an observational, 2 phase, patient reported outcomes study. AB - BACKGROUND: We designed the PROXIMA study (Patient-Reported Outcomes and Xolair((r)) In the Management of Asthma) to determine the proportion of patients with severe asthma sensitive to perennial allergens, and to evaluate asthma control and treatment adherence up to 12 months in patients treated with omalizumab in Italian population. In addition, an ancillary study was designed to explore protein biomarkers and characterize them in relation to severe allergic asthma and treatment effects by proteomic approach. METHODS: PROXIMA is an observational, multicenter, cross-sectional and prospective cohort study conducted at 25 centers in Italy, in outpatient settings. The study consists of two phases: 1) a cross-sectional phase plans to enroll 600 patients with severe allergic asthma, in step 4 therapy as per GINA guidelines, aged >=18 years, needing a step up in therapy, and 2) a longitudinal phase on patients who will start omalizumab add-on therapy per clinician's judgment at baseline visit (approximately 180-240 patients). The primary variable of the cross-sectional phase is the proportion of patients with severe asthma presenting with perennial form of allergy (skin prick test or in vitro test). The primary variable of longitudinal phase is proportion of patients who achieve disease control (assessed by Asthma Control Questionnaire [ACQ]) with omalizumab at 6 months, and maintain it at 12 months. Secondary variables are patient compliance to omalizumab, patient-reported perception of cognitive and emotional impact of the illness, assessed by Brief Illness Perception Questionnaire (Brief IPQ) and the health related quality of life evaluated by the EuroQoL 5D-3 L (EQ-5D-3 L). Safety endpoints will be recorded during the course of the study. Patients participating in the longitudinal phase will be enrolled for ancillary study if they provide additional informed consent. Protein species in complex mixtures will be identified using innovative MudPIT (Multidimensional Protein Identification Technology) method. CONCLUSIONS: The results of this observational study will provide estimate of patient population allergic to perennial allergens in Italy and information on patient-reported outcomes with omalizumab therapy in a real-world setting. The exploratory proteomic analysis on asthma biomarkers could eventually provide new data to identify responder patients to anti IgE therapy. PMID- 26155197 TI - Erratum: Prevalence of positive atopy patch test in an unselected pediatric population. AB - [This corrects the article DOI: 10.1186/s12948-015-0011-2.]. PMID- 26155198 TI - Discovery of porcine maternal factors related to nuclear reprogramming and early embryo development by proteomic analysis. AB - BACKGROUND: Differentiated cell nuclei can be reprogrammed to a pluripotent state in several ways, including incubation with oocyte extracts, transfer into enucleated oocytes, and induced pluripotent stem cell technology. Nuclear transfer-mediated reprogramming has been proven to be the most efficient method. Maternal factors stored in oocytes have critical roles on nuclear reprogramming and early embryo development, but remain elusive. RESULTS: In this study, we showed most of porcine oocytes became nuclear matured at 33 h of IVM and the rate had no significant difference with oocytes at 42 h of IVM (p > 0.05). Moreover, the cleavage and blastocyst rates of SCNT and PA embryos derived from 42O were significantly higher than that of 33O (p < 0.05). But 33O could sustain IVF embryo development with higher cleavage and blastocyst rates comparing to 42O (p < 0.05). To clarify the development potential difference between 33O and 42O, 18 differentially expressed proteins were identified by proteomic analysis, and randomly selected proteins were confirmed by Western blot. Bioinformatic analysis of these proteins revealed that 33O highly synthesized proteins related to fertilization, and 42O was rich in nuclear reprogramming factors. CONCLUSIONS: These results present a unique insight into maternal factors related to nuclear reprogramming and early embryo development. PMID- 26155199 TI - How much might a society spend on life-saving interventions at different ages while remaining cost-effective? A case study in a country with detailed data. AB - OBJECTIVE: We aimed to estimate the maximum intervention cost (EMIC) a society could invest in a life-saving intervention at different ages while remaining cost effective according to a user-specified cost-effectiveness threshold. METHODS: New Zealand (NZ) was used as a case study, and a health system perspective was taken. Data from NZ life tables and morbidity data from a burden of disease study were used to estimate health-adjusted life-years (HALYs) gained by a life-saving intervention. Health system costs were estimated from a national database of all publicly funded health events (hospitalizations, outpatient events, pharmaceuticals, etc.). For illustrative purposes we followed the WHO-CHOICE approach and used a cost-effectiveness threshold of the gross domestic product (GDP) per capita (NZ$45,000 or US$30,000 per HALY). We then calculated EMICs for an "ideal" life-saving intervention that fully returned survivors to the same average morbidity, mortality, and cost trajectories as the rest of their cohort. FINDINGS: The EMIC of the "ideal" life-saving intervention varied markedly by age: NZ$1.3 million (US$880,000) for an intervention to save the life of a child, NZ$0.8 million (US$540,000) for a 50-year-old, and NZ$0.235 million (US$158,000) for an 80-year-old. These results were predictably very sensitive to the choice of discount rate and to the selected cost-effectiveness threshold. Using WHO data, we produced an online calculator to allow the performance of similar calculations for all other countries. CONCLUSIONS: We present an approach to estimating maximal cost-effective investment in life-saving health interventions, under various assumptions. Our online calculator allows this approach to be applied in other countries. Policymakers could use these estimates as a rapid screening tool to determine if more detailed cost-effectiveness analyses of potential life-saving interventions might be worthwhile or which proposed life saving interventions are very unlikely to benefit from such additional research. PMID- 26155200 TI - Spontaneous and transgenic rodent models of inflammatory bowel disease. AB - Inflammatory Bowel Disease (IBD) is a multifactorial disorder with many different putative influences mediating disease onset, severity, progression and diminution. Spontaneous natural IBD is classically expressed as Crohn's Disease (CD) and Ulcerative Colitis (UC) commonly found in primates; lymphoplasmocytic enteritis, eosinophilic gastritis and colitis, and ulcerative colitis with neuronal hyperplasia in dogs; and colitis in horses. Spontaneous inflammatory bowel disease has been noted in a number of rodent models which differ in genetic strain background, induced mutation, microbiota influences and immunopathogenic pathways. Histological lesions in Crohn's Disease feature noncaseating granulomatous inflammation while UC lesions typically exhibit ulceration, lamina propria inflammatory infiltrates and lack of granuloma development. Intestinal inflammation caused by CD and UC is also associated with increased incidence of intestinal neoplasia. Transgenic murine models have determined underlying etiological influences and appropriate therapeutic targets in IBD. This literature review will discuss current opinion and findings in spontaneous IBD, highlight selected transgenic rodent models of IBD and discuss their respective pathogenic mechanisms. It is very important to provide accommodation of induced putative deficits in activities of daily living and to assess discomfort and pain levels in the face of significant morbidity and/or mortality in these models. Epigenetic, environmental (microbiome, metabolome) and nutritional factors are important in IBD pathogenesis, and evaluating ways in which they influence disease expression represent potential investigative approaches with the greatest potential for new discoveries. PMID- 26155201 TI - Prolonged oral administration of Gastrodia elata extract improves spatial learning and memory of scopolamine-treated rats. AB - Gastrodia elata (GE) is traditionally used for treatment of various disorders including neurodegenerative diseases such as Alzheimer's disease. To investigate the neuroprotective effect of GE, amyloid-beta peptide (Abeta)-treated PC12 cells were cultured with GE aqueous extract. In vitro assay demonstrated that 50 uM of pre-aggregated Abeta was lethal to about a half portion of PC12 cells and that Abeta aggregate-induced cell death was significantly decreased with GE treatment at <=10 mg/mL in a dose-dependent manner. To further examine in vivo cognitive improving effects, an artificial amnesic animal model, scopolamine-injected Sprague-Dawley rats, were orally administered the extract for 6 weeks followed by behavioral tests (the passive avoidance test and Morris water maze test). The results showed that an acute treatment with scopolamine (1 mg/kg of body weight) effectively induced memory impairment in normal rats and that the learning and memory capability of scopolamine-treated rats improved after prolonged administration of GE extract (50, 250 and 500 mg/kg of body weight for 6 weeks). These findings suggest that a GE regimen may potentially ameliorate learning and memory deficits and/or cognitive impairments caused by neuronal cell death. PMID- 26155202 TI - Tumor necrosis factor-alpha deficiency impairs host defense against Streptococcus pneumoniae. AB - Streptococcus pneumoniae is a major human pathogen that is involved in community acquired pneumonia. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that activates immune responses against infection, invasion, injury, or inflammation. To study the role of TNF-alpha during S. pneumoniae infection, a murine pneumococcal pneumonia model was used. We intranasally infected C57BL/6J wild-type (WT) and TNF-alpha knockout (KO) mice with S. pneumoniae D39 serotype 2. In TNF-alpha KO mice, continuous and distinct loss of body weight, and low survival rates were observed. Bacterial counts in the lungs and blood of TNF alpha KO mice were significantly higher than those in WT mice. Histopathological lesions in the spleen of TNF-alpha KO mice were more severe than those in WT mice. In TNF-alpha KO mice, severe depletion of white pulp was observed and the number of apoptotic cells was significantly increased. Interferon-gamma (IFN gamma), IL-12p70 and IL-10 levels in serum were significantly increased in TNF alpha KO mice. TNF-alpha is clearly involved in the regulation of S. pneumoniae infections. Early death and low survival rates of TNF-alpha KO mice were likely caused by a combination of impaired bacterial clearance and damage to the spleen. Our findings suggest that TNF-alpha plays a critical role in protecting the host from systemic S. pneumoniae infection. PMID- 26155203 TI - Comparison of three diagnostic assays for the identification of Helicobacter spp. in laboratory dogs. AB - A number of Helicobacter species may confound experimental data because of their association with disease progressing in various kinds of laboratory animals. Screening of Helicobacter species is particularly desirable, because they are prevalent in commercial and research animal facilities. The aim of the present study was to compare three diagnostic methods [e.g. Helicobacter stool antigen kit (HpSA), polymerase chain reaction (PCR) and rapid urease test (RUT)] for the identification of Helicobacter spp. in stools or gastric biopsy specimens collected from eight dogs suffering from gastritis. The gastroscopic biopsy specimens were tested using RUT and PCR, while stool specimens were evaluated using both HpSA and PCR. DNAs from the gastric biopsies and stool specimens were analyzed by both a consensus PCR that amplified the RNA polymerase beta-subunit coding gene (rpoB) of Helicobacter spp. and a species-specific PCR to amplify the urease B gene of Helicobacter heilmannii, Helicobacter pylori, and Helicobacter felis. Helicobacter spp. were detected in 62.5% of the dogs, while H. heilmannii and H. felis were identified in 37.5 and 25% of the dogs, respectively. The HpSA did not efficiently detect Helicobacter spp. in the stool samples compared to the RUT and PCR assays, both of which successfully detected Helicobacter spp. in the two sample types. Finally, we recommend that consensus PCR with stool specimens could be used before the species-specific PCR for identifying Helicobacter species in laboratory dogs. PMID- 26155204 TI - Expression of pancreatic and duodenal homeobox1 (PDX1) protein in the interior and exterior regions of the intestine, revealed by development and analysis of Pdx1 knockout mice. AB - We developed pancreatic and duodenal homeobox1 (Pdx1) knockout mice to improve a compensatory hyperinsulinemia, which was induced by hyperplasia in the beta cells or Langerhans' islands, as the diabetic model mice. For targeting of Pdx1 gene by homologous recombination, ES cells derived from a 129(+Ter) /SvJcl*C57BL/6JJcl hybrid mouse were electroporated and subjected to positive-negative selection with hygromycin B and ganciclovir. As these results, one of the three chimeric mice succeeded to produce the next or F1 generation. Then, the mouse fetuses were extracted from the mother's uterus and analyzed immunohistologically for the existence of a pancreas. The fetuses were analyzed at embryonic day 14.5 (E14.5) because Pdx1 knockout could not alive after birth in this study. Immunohistochemical staining revealed that 10 fetuses out of 26 did not have any PDX1 positive primordium of the pancreas and that the PDX1 expresses in both the interior and exterior regions of intestine. In particular, one the exterior of the intestine PDX1 was expressed in glands that would be expected to form the pancreas. The result of PCR genotyping with extracted DNA from the paraffin sections showed existence of 10 Pdx1-knockout mice and corresponded to results of immunostaining. Thus, we succeeded to establish a Pdx1-knockout (Pdx1 (-/-)) mice. PMID- 26155205 TI - Erratum: In vitro and in vivo anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract. AB - [This corrects the article on p. 28 in vol. 30, PMID: 24707302.]. PMID- 26155206 TI - Liver retransplantation for adult recipients. AB - Living donor liver graft can be used for the first or second liver transplantation. The timing of retransplantation also should be stratified as 2 types according to the reoperation timing. Combination of these two classifications results in 6 types of living donor liver transplantation (LDLT) associated retransplantation. However, late retransplantation to LDLT might have not been performed in most LDLT programs, thus other 4 types of LDLT-associated retransplantation can be taken into account. The most typical type of LDLT associated retransplantation might be early living donor-to-deceased donor retransplantation. For early living donor-to-living donor retransplantation, its eligibility criteria might be similar to those of early living donor-to-deceased donor retransplantation. For early deceased donor-to-living donor retransplantation, its indications are exactly the same to those for aforementioned living donor-to-living donor retransplantation. Late deceased donor retransplantation after initial LDLT has the same indication for ordinary late deceased donor retransplantation. PMID- 26155207 TI - Pancreas club international joint symposium on pancreatic cancer 2012, Kyoto: down staging chemo+/-radiotherapy for borderline resectable pancreatic cancer. AB - This manuscript summarized one section out of the international symposium, Pancreatic Cancer 2012, which was held last October 4th through 6th in Kyoto (Japan) under the theme, "We are the Team: Opening the Door to the Next Step for Pancreatic Cancer Therapy." Borderline resectable pancreatic cancer (BRPC) is a specific clinical presentation with features in between those of resectable and locally advanced pancreatic cancers. The classification of pancreatic cancer is an important issue given that a cancer may look resectable but be high-risk for R1 or R2 resection. Considering that margin-negative resection is a fundamental requirement for curing pancreatic cancer, this issue is one of the most interesting to pancreatic surgeons. At Pancreatic Cancer 2012 in Kyoto, BRPC was also discussed at the Pancreatic Club International Joint Symposium. In this manuscript, the contents of the presented topics are briefly summarized to facilitate understanding of recent issues in managing BRPC. PMID- 26155208 TI - Living donor liver transplantation for patients with alcoholic liver disease. AB - BACKGROUNDS/AIMS: Since most transplantation studies for alcoholic liver disease (ALD) were performed on deceased donor liver transplantation, little was known following living donor liver transplantation (LDLT). METHODS: The clinical outcome of 18 ALD patients who underwent LDLT from Febraury 1997 to December 2004 in a large-volume liver transplantation center was assessed retrospectively. RESULTS: The model for end-stage liver disease score was 23+/-11, and mean pretransplant abstinence period was 16+/-13 months, with 14 (77.8%) patients being abstinent for at least 6 months. Graft types were right lobe grafts in 11, left lobe grafts in 2 and dual grafts in 5. Graft to recipient body weight ratio was 0.94+/-0.16. The relapse rates in patients who did and did not maintain 6 months of abstinence were 7.1% and 50%, respectively (p=0.097). Younger recipient age was a significant risk factor for alcohol relapse (p=0.027). Five recipients with antibody to hepatitis B surface antigen (HBsAg) received core antibody positive liver graft, but two of them showed positive HBsAg seroconversion. Overall 5-year patient survival rate following LDLT was 87.8%, with a 5-year relapse rate of 16.7%. CONCLUSIONS: Pretransplant abstinence for 6 months appears to be benefical for preventing posttransplant relapse. Life-long prophylactic measure should be followed after use of anti-HBc-positive liver grafts regardless of hepatitis B viral marker status of the recipient. PMID- 26155209 TI - Therapeutic potentials occurring during the early differentiation process of mesenchymal stem cells in a rats model with thioacetamide-induced liver fibrosis. AB - BACKGROUNDS/AIMS: Mesenchymal stem cells (MSCs) have the capacity to differentiate into hepatocytes, The purpose of this study is to investigate the MSCs' differentiation process and therapeutic potentials by comparing isolated MSCs with HGF-treated MSCs in rat's model with thiacetamide (TAA)-induced cirrhosis. METHODS: Male Sprague-Dawley (SD) rats, weighing 100-150 g were used in this study. To induce liver fibrosis, recipient rats were taken with 0.04% thioacetamide (TAA) in the drinking water (400 mg TAA/L) for 8 weeks. The rats underlying liver cirrhosis were divided into 3 groups according to the transplanted materials, compared to normal saline as control (I) and isolated MSCs (II) HGF-treated MSCs. RESULTS: Severe hepatic fibrosis and hepatocyte destruction were detected in the control group. Less hepatic cirrhosis and collagen formation, more hepatocyte regeneration and glycogen storage were detected in isolated MSCs compared to HGF-treated MSCs group, Distribution of red autofluorescence is mainly localized near the sinusoids in isolated MSCs, scattered away the sinusoids in HGF-treated MSCs group. MSCs transdifferentiated into CK-19 postive Oval cells and then to albulmin-producing hepatocytes, HGF treated MSCs differentiated into hepatocyte without the intermediate oval cells phase. HGF treated MSCs became the CK18-positive, MSCs became CD 90-positive. CONCLUSIONS: Significant hepatocyte differentiation occurred in not HGF-treated MSCs but isolated MSCs group unexpectedly. These results suggest that the beneficial effect of MSCs on in rat's model with TAA-induced cirrhosis may occur during early differentiation course of MSCs. Mature hepatocyte itself has a little effect on the accelerated differentiation and functional capacity of hepatic lineage cell-line. PMID- 26155210 TI - Primary hepatic neuroendocrine carcinoma. AB - A 67-year-old woman was admitted to our hospital under suspicion of a hepatic tumor, which had been previously diagnosed to be an adenocarcinoma by fine needle aspiration. Computed tomography and magnetic resonance imaging revealed a large tumor measuring 9 cm in diameter in Couinaud's hepatic segments 4, 5, and 8. We diagnosed the patient to have primary liver cancer, and suspected intrahepatic cholangiocarcinoma preoperatively. We performed a central hepatectomy. According to the immunohistochemical findings of the resected specimen, the tumor was diagnosed to be a primary neuroendocrine carcinoma in the liver. The patient is presently alive without recurrence at 3 months after hepatic resection. PMID- 26155211 TI - A case of primary adenosquamous carcinoma of the liver. AB - Adenosquamous carcinoma (ASC) is a rare tumor of the liver, which carries a poor prognosis. It has been reported mostly in the form of case studies. Recently, we experienced a case of primary ASC of the liver that has been preoperatively considered as cholangiocelluar carcinoma of the liver. Microscopically, the tumor was composed of adenocarcinoma, squamous cell carcinoma, as well as transitional area, including the transformation of adenocarcinoma to squamous cell carcinoma. The patient remained well with no evidence of post-resection complication or recurrence for 15 month. PMID- 26155212 TI - Spontaneous rupture of intrahepatic bile duct following portal vein embolization in a patient with perihilar cholangiocarcinoma: a case of successful curative resection. AB - We herein present a case of spontaneous rupture of intrahepatic bile duct in a patient with perihilar cholangiocarcinoma, which were successfully treated by curative resection. A 60-year-old male patient with perihilar cholangiocarcinoma was decompressed with single percutaneous transhepatic biliary drainage. Two days after right portal vein embolization, the patient suffered from paralytic ileus with marked abdominal distension. Imaging study revealed that marked fluid collection around the liver and whole abdomen, suggesting intrahepatic bile duct rupture. With abdominal drainage and biliary decompression for 2 weeks, the biliary rupture was controlled. To enhance the safety of right hepatectomy, additional right hepatic vein embolization was performed. The patient underwent routine surgical procedures for right hepatectomy, caudate lobectomy and bile duct resection, and recovered uneventfully and discharged 18 days after surgery. This is the first report of a case of spontaneous rupture of intrahepatic bile duct in a patient with perihilar cholangiocarcinoma. PMID- 26155213 TI - Intrahepatic and extrahepatic intraductal papillary neoplasms of bile duct. AB - There has been an increase in the number of reported cases of biliary neoplasm of the hepatobiliary system characterized by markedly dilated and multifocal papillary epithelial lesions of the bile ducts or cystic biliary lesions with or without mucin secretion, and mucinous lesions or tumors, possibly due to recent advances in radiological diagnosis. This lesion of the bile duct is believed to show a better clinical course than non-papillary biliary neoplasm. Therefore, the early recognition and treatment is important. We report two cases of intrahepatic and extrahepatic intraductal papillary neoplasm of the bile duct that were completely resected. PMID- 26155214 TI - Hepatogenic differentiation of human mesenchymal stem cells from peritoneal adipose tissue. AB - BACKGROUNDS/AIMS: It has been reported that functional hepatogenic differentiation has the possibility to occur in subcutaneous adipose tissue derived stem cells. However, no studies have investigated whether the adipose tissue-driven stem cells present in various body parts differ according to hepatogenic differentiations. In this study, stem cells were separated from body visceral fat and abdominal subcutaneous adipose tissue, and cultured, and then hepatogenic differentiation was induced. We aim to investigate the possibilities and aspects of hepatogenic differentiations within the two types of fat cells. METHODS: Omental fat tissues were obtained as visceral fat and abdominal subcutaneous adipose tissues were obtained from patients who had suction-assisted lipectomy. Stem cells were separated from the obtained fat tissues, and then, hepatogenic differentiation was carried out by utilizing 2-step differentiation protocols. RESULTS: After the differentiation, two types of cultured cells that showed the similar neuron-like shapes were changed to cuboidal shapes and included several binucleated cells which could be characteristics of mature hepatocytes. We confirmed that hepatocyte specific genes and proteins such as albumin and CYP3A4 were being expressed. By utilizing the ELISA test, we were able to observe that the albumin was secreted into the culture fluids in both cells. After completing the differentiation, we observed the presence of the hepatocyte specific properties by confirming glycogen storage within the cells and the ICG reagent uptake. CONCLUSIONS: We confirmed that hepatogenic differentiation was possible to occur in the omental fat as well as subcutaneous adipose tissue. PMID- 26155215 TI - Delayed laparoscopic cholecystectomy after more than 6 weeks on easily controlled cholecystitis patients. AB - BACKGROUNDS/AIMS: There is debate on the timing of cholecystectomy in acute cholecystitis. Although there is a recent trend toward early laparoscopic cholecystectomy (eLC), that is, within 72 hours of symptom onset, some surgeons still prefer delayed operations, or operations after several weeks, expecting subsidence of the inflammation and therefore a higher chance of avoiding open conversion and minimizing complications. Our experience of LC for 10 years was reviewed retrospectively for the timing of the operation and perioperative outcomes, focusing on evaluating the feasibility of delayed LC (dLC). METHODS: The severity of the acute cholecystitis was classified into three grades: easily responding to antibiotics and mostly symptom-free (mild, grade I), symptoms persisting during the treatment (moderate, grade II), and worsening into a septic state (severe, grade III). RESULTS: Among 353 cholecystectomy patients, grade I (N=224) patients had eLC in 152 cases and dLC in 72 cases. Grade II (N=117) patients had eLC in 103 cases and 12 had dLC. All grade III patients (N=12) underwent open cholecystectomy. In Grade I patients, when the operation was delayed, there were fewer open conversion cases compared to eLC patients (20.45% vs 7.69%) (p<0.05), and complications also were decreased (p>0.05). Grade II patients' rate of open conversions (58.3% vs 44.2%) and complications (25.0% vs 19.5%) increased when the operations were delayed compared with eLC patients (p<0.05). In grade I and II patients, the most common reason for open conversion was bleeding, and the most common complication was also bleeding. CONCLUSIONS: For patients with cholecystits that easily responds to antibiotics (grade I), dLC showed a higher laparoscopic success rate than eLC at the expense of prolonged treatment time and examinations, With moderate to severe cholecystitis (grade II, III), however, there was no room for delayed operations. PMID- 26155216 TI - Fate of lost gallstones during laparoscopic cholecystectomy. AB - BACKGROUNDS/AIMS: The fate of gallstones that remain in the peritoneal cavity due to perforation of the gallbladder during laparoscopic cholecystectomy (LC) has been studied vigilantly since the early 1990s when this surgical procedure started to be used. But the complication statistics vary with each report. So we reviewed our 47 cases of lost stones that were traceable from 1998 to 2007. METHODS: Stones entered the peritoneal cavity through the perforation site during dissection of the body or Hartmann's pouch of gallbladder from the liver bed, despite trials of stone removal like irrigation and using a glove finger pouch especially in the case of numerous small stones. There were nine cases of lost stones that were caused by fragments of stone breaking from a large stone during its retrieval. RESULTS: No patient was forced into revision surgery or intervention for the missing stones but only negative suction drains were inserted, and information to the patients was given. Most of the stones (N=42, 89.4%) remained silent during the follow-up period of 10.4+/-3.6 years, and 5 patients (10.6%) developed inflammatory complications in the peritoneal cavity and abdominal wall. Two intraperitoneal abscesses were found in the right subhepatic area and a cul-de-sac and these were managed by laparotomy. Subhepatic abscess was later associated with intestinal obstruction. Two patients suffered an umbilical portal site fistula and a right flank portal fistula respectively, requiring prolonged wound care. One patient suffered immediate postoperative peritonitis that was cured by antibiotics. CONCLUSIONS: Lost stones should be retrieved or fragmented as much as possible for removal through a drain, and caution should be exercised during dissection of the gallbladder to avoid perforating the gallbladder. Considering the approximately 10% incidence of serious inflammatory complications of lost stones, the complications should be explained to patients to allow for earlier diagnosis of complications later. PMID- 26155217 TI - Ten-year experience on common bile duct exploration without T-tube insertion. AB - BACKGROUNDS/AIMS: Common bile duct (CBD) exploration has been a procedure necessary to remove stones which are not removable by endoscopic sphincterotomy (EST). T-tube was installed mainly in the concern of bile leakage after procedure. But T-tube itself can only cause bile peritonitis and thus, prolonged discomfort and care after operation. In addition, in the era of laparoscopy, T tube insertion adds much operation time and is technically difficult for installation during the procedure. METHODS: Our case of open cholecystectomy and primary closure of CBD not leaving T-tube (n=28, group I) with reports dating from July 1998 to June 2007 is presented here to see whether primary closure without T-tube is safe as compared with T-tube inserted cases performed at the same center (n=15, group II). Operative cholangiography, CT scan, ultrasound and biochemical data were followed up for both groups and surveyed on operative complications as well to determine the outcomes. RESULTS: Bile leakage in 1, recurrent stone in 2 and obstructive jaundice in 1 were all considered during the follow up period among 28 group I patients (n=6), when compared to T-tube inserted group II patients with 2 bile peritonitis, 1 residual stones and 1 pancreatitis (n=4), showing no meaningful differences (p=0.07). CONCLUSIONS: CBD exploration and direct primary closure not leaving T-tube is an acceptable operational option as recently tried in many choledochotomies. PMID- 26155218 TI - Closure of pancreatoduodenal fistula using vascular occluding coil embolization and fibrin glue injection: a case study. AB - The conventional management of pancreatoenteric fistulas and pancreatic abscess with aggressive surgery or percutaneous drainage catheter placement are associated with increased surgery-related morbidity and mortality, and a longer hospitalization. We report here a case of successful closing pancreatoduodenal fistula, which remained open after the percutaneous catheter drainage of pancreatic abscess, by using vascular coil embolization and fibrin glue injection. This procedure is a less invasive, more effective and better tolerated strategy for the management of pancreatoenteric fistula in a selected group of high risk patients and needs further investigation. PMID- 26155219 TI - Laparoscopic treatment for post-cholecystectomy Mirizzi syndrome. AB - The remnant cystic duct or gallbladder neck calculus may rarely result in post cholecystectomy Mirizzi syndrome. Various managements have been proposed for the treatment of post-cholecystectomy Mirizzi syndrome. Some previous cases of post cholecystectomy Mirizzi syndrome have been managed with open cholecystectomy and endoscopically. We report a case of a laparoscopic stone removal of post cholecystectomy Mirizzi syndrome that developed 7 months after laparoscopic cholecystectomy. To our knowledge, this is the first case of laparoscopic management of post-cholecystectomy Mirizzi syndrome. The mechanism, diagnosis and treatment of post-cholecystectomy Mirizzi syndrome are discussed. PMID- 26155220 TI - Acute acalculous cholecystitis after laparoscopic appendectomy in a young healthy patient: report of a case. AB - Acute acalculous cholecystitis (AAC) is defined as acute inflammation of the gallbladder in the absence of gallstones. AAC occurs in patients after major surgery and in the presence of serious co-morbidities such as severe trauma, burns, sepsis, prolonged intravenous hyperalimentation and hemodynamic instability. AAC is rare in patients with none of the established risk factors. We present a case of a 38-year-old woman who developed AAC after laparoscopic appendectomy. PMID- 26155221 TI - Delayed presentation of traumatic diaphragmatic rupture with complicated cholecystitis. AB - The right-sided diaphragmatic rupture is often clinically occulted due to buffering effects of the liver and thus, erroneous diagnosis of such rupture may result in life-threatening conditions. A 44-year-old female who had a history of car accident in 2006 was admitted to our hospital for pleuritic pain. On the chest computed tomography, she was diagnosed with diaphragmatic rupture accompanied by herniation of hypertrophic left liver with complicated cholecystitis and we carried out cholecystectomy, reduction of the liver, pleural drainage, and primary closure of the diaphragm via thoracic approaches. Our case is presented in three unique aspects: herniation of left hemiliver, hypertrophic liver herniated up to the 4(th) rib level, and combination of complicated cholecystitis. Although the diagnosis of right-sided diaphragmatic rupture can be challenging for the surgeon, an early diagnosis can prevent further complications on the clinical presentation. PMID- 26155222 TI - Fenofibrate, a peroxisome proliferator-activated receptor alpha-agonist, blocks lipopolysaccharide-induced inflammatory pathways in mouse liver. AB - BACKGROUNDS/AIMS: During the acute phase response, cytokines induce marked alterations in lipid metabolism including an increase in serum triglyceride levels and a decrease in hepatic fatty acid oxidation, in bile acid synthesis, and in high-density lipoprotein levels. METHODS: Peroxisome proliferator activated receptors (PPARs: PPARalpha, beta/delta, and gamma) regulate fatty acid metabolism, glucose homeostasis, cell proliferation, differentiation and inflammation. Proinflammatory profiles including tumor necrosis factor alpha (TNF alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) are the important pathological factors in inflammatory responses during the pathological progression of the acute phase response. Lipopolysaccarides (LPS) induced the expression of TNF-alpha, IL-1beta, and IL-6. LPS-induced inflammation decrease the expression of peroxisome proliferator-activated receptor alpha (PPARalpha), PPARbeta/delta, PPARgamma, and coactivators PPARgamma co-activator 1 alpha (PGC 1alpha), PGC-1beta messenger RNA (mRNA) in the liver of Balb/c mouse. In addition, LPS-induced inflammation diminishes the protein level of PPARalpha, PPARbeta/delta, and PPARgamma. Proinflammatory cytokines including TNFalpha, IL 1beta, and IL-6 are the principal reducer of PPARs. However, the knockout mouse model against TNFalpha and IL-6 does not block decrease of PPARs in serum and liver. The mice were pretreated with fenofibrate at 100 mg/kg for 2 days. RESULTS: These treatment protocols increased the amount of PPARs mRNA in the liver. Fenofibrate inhibited LPS-induced TNF-alpha, IL-1beta, and IL-6 production in the serum and liver. Similar results were obtained when human hepatoma HepG2 cells exposed to LPS were co-incubated with fenofibrate. LPS-treated HepG2 cells decreased expression of IkappaB. Moreover, activation of PPARs abrogated LPS induced degradation of IkappaB, thus suppressing LPS-induced NF-kappaB activities. CONCLUSIONS: Therefore, fenofibrate decreases the expression and secretion of TNF-alpha, IL-1beta, and IL-6 via the NF-kappaB signaling pathway, thus serving as therapeutic targets to attenuate inflammation that is involved in hepatic pathological progression. PMID- 26155223 TI - Technical knacks and outcomes of extended extrahepatic bile duct resection in patients with mid bile duct cancer. AB - BACKGROUNDS/AIMS: Mid bile duct cancers often involve the proximal intrapancreatic bile duct, and resection of the extrahepatic bile duct (EHBD) can result in a tumor-positive distal resection margin (RM). We attempted a customized surgical procedure to obtain a tumor-free distal RM during EHBD resection, so that R0 resection can be achieved without performing pancreaticoduodenectomy through extended EHBD resection. METHODS: We previously reported the surgical procedures of extended EHBD resection, in which the intrapancreatic duct excavation resembles a >=2 cm-long funnel. This unique procedure was performed in 11 cases of mid bile duct cancer occurring in elderly patients between the ages of 70 and 83 years. RESULTS: The tumor involved the intrapancreatic duct in all cases. Deep pancreatic excavation per se required about 30-60 minutes. Cancer-free hepatic duct RM was obtained in 10 patients. Prolonged leakage of pancreatic juice occurred in 2 patients, but all were controlled with supportive care. Adjuvant therapies were primarily applied to RM positive or lymph node-positive patients. Their 1-year and 3-year survival rates were 90.9% and 60.6%, respectively. CONCLUSIONS: We suggest that extended EHBD resection can be performed as a beneficial option to achieve R0 resection in cases in which pancreaticoduodenectomy should be avoided due to various causes including old age and expectation of a poor outcome. PMID- 26155224 TI - Prognosis of patients with pT1b/T2 gallbladder carcinoma who have undergone laparoscopic cholecystectomy as an initial operation. AB - BACKGROUNDS/AIMS: Laparoscopic cholecystectomy (LC) has become a standard procedure for treatment of benign gallbladder diseases. There has been a small proportion of gallbladder cancer (GBC) which was incidentally found in the gallbladder specimen, and LC has been tried in some patients with faintly suspected GBC. This study intended to analyze the prognosis of patients with pT1b/T2 GBC who have undergone LC and the outcome of extended re-operation. METHODS: After analyzing the institutional profiles of 500 GBC patients who have undergone surgical resection, we selected 64 patients who underwent LC initially from January 1996 to December 2008 and whose gallbladder pathology was confined to pT1b or pT2 lesions. Of them, 34 patients (53.1%) underwent extended reoperation. Their medical records were reviewed retrospectively. RESULTS: In the LC only group (n=30), mean age of the 16 pT1 patients was 65.7+/-12.5 years and mean age of the 14 pT2 patients was 66.7+/-10.1 years. In the reoperation group (n=34), mean age of the 8 pT1b patients was 52.6+/-9.9 years and in 26 pT2 patients, mean age was 59.2+/-7.9 years. The reoperation group showed a younger patient age pattern than the LC only group (p=0.001). The types of reoperation were liver resection with lymph node (LN) dissection in 17, bile duct resection with LN dissection in 2, and hepatectomy and bile duct resection with LN dissection in 15. In the LC only group, the 5-year survival rate (5-YSR) was 70.3% in pT1b and 43.2% in pT2. In the reoperation group, 5-YSR was 62.5% in pT1b (n=8) and 59.5% in pT2 (n=26). A survival comparison between the two groups showed no significant survival gain in pT1 patients (p=0.69) and in pT2 patients (p=0.14). In our whole database analysis, 5-YSR of pT1bNx lesions was 70% after cholecystectomy and 78% after extended cholecystectomy. Lymph node metastasis was identified in 11% of pT1b lesions. For pT2N0 lesions, overall 5-YSR was 62% after R0 resection, showing no survival difference between primary extended surgery and LC-redo operation (p=0.45). CONCLUSIONS: The survival gain of reoperation was not evident in pT1b lesions. In contrast, some noticeable but not statistically significant survival difference was observed in pT2 lesions. Thus, reoperation for pT1b/T2 GBC following LC is indicated for individualized reasons, especially in patients with pT1b lesions. Old age was one of the important factors in deciding not to reoperate. PMID- 26155225 TI - Surgical management and results for cystic neoplasms of pancreas. AB - BACKGROUNDS/AIMS: The diagnosis for cystic neoplasm of pancreas is based on the morphologic criteria through imaging studies, but the pre- and postoperative diagnoses are often inconsistent. This study aims at the analysis of clinical characteristics and the results of surgical treatments. METHODS: A retrospective review was performed on 93 patients who have undergone surgery for pancreatic cystic diseases in our hospital from January 2001 to February 2013. Among them, 69 patients were confirmed as cystic neoplasms based on pathologic findings. Their clinical manifestations, diagnostic accuracy, surgical method and complications, pathologic findings were analyzed. RESULTS: Serous cystic neoplasm was the most common (n=22), followed by mucinous cystic neoplasm (n=18), intraductal papillary mucinous tumor (n=11), solid pseudopapillary tumor (n=9), neuroendocrine tumor (n=7), and cystic lymphangioma (n=2). The most common clinical symptom is abdominal pains (49.3%). Preoperative imaging studies were consistent with pathological findings in 72% of patients. Cystic fluid CEA levels of 400 ng/ml or more were reliable to detect mucin secreting tumors. Pancreatoduodenectomy was performed for 13 cases and the remaining 54 patients were treated with left-side pancreatectomy. Malignancy was found in 9 cases (13%) of mucin secreting tumors; 5 cases (27.8%) in mucinous cystic neoplasm and 4 cases (36.4%) in intraductal papillary mucinous tumor. Two of these survived without recurrences during the follow-up periods. CONCLUSIONS: Exact treatment protocols for cystic neoplasm of pancreas are not decided because tumors are found with atypical forms. Surgical management is suggested for resectable tumors because a good prognosis can be expected with proper surgery if precancerous lesions are suspected at the time of discovery. PMID- 26155226 TI - Duodenum-preserving pancreatic head resection in benign and low-grade malignant pancreatic tumors. AB - BACKGROUNDS/AIMS: With development of imaging techniques, pancreatic tumors are being diagnosed more frequently. Applying the standard surgical procedures for pancreatic head tumors, such as pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy may seem too extensive for benign or low-grade malignant pancreas head tumors. Duodenum-preserving pancreatic head resection (DPPHR) has been safely performed in patients with chronic pancreatitis. Recently, DPPHR has been used as a limited surgical procedure to remove benign or low-grade malignant pancreatic head lesions. This study is aimed to evaluate the results of DPPHR in benign or low-grade malignant tumors. METHODS: Between 2004 and 2012, six patients underwent DPPHR due to benign or low-grade malignant pancreas tumor. We performed this retrospective analysis based on the medical records. RESULTS: Five of six patients were diagnosed as intraductal papillary mucinous neoplasms. Remaining one patient was diagnosed as solid pseudopapillary neoplasm. The median age of patients was 60.3 (27-75) years, and the median follow-up period was 24 months. The operation time, blood loss and length of stay were 442.5 minutes, 680 ml and 19.2 days, respectively. There was no mortality. Five patients experienced complications including 1 delayed gastric empting, 2 bile duct strictures, 1 pancreatic fistula and 1 duodenal stricture. No recurrence or metastasis was found during follow-up. CONCLUSIONS: In benign and low-grade malignant lesions of pancreatic head, DPPHR could be alternative to traditional surgery. For applying DPPHR in pancreas tumor, a thorough preoperative examination and utilization of frozen section for sufficient resection margin are required. PMID- 26155227 TI - Peribiliary cysts developed in normal underlying liver: report of a case. AB - Peribiliary cysts, known as cystic dilatation, of the extramural peribiliary glands of the bile duct are rare, and are usually detectable under conditions of pre-existing hepatobiliary diseases such as liver cirrhosis. Preoperative diagnosis is often difficult, because they are usually asymptomatic. Distinction of peribiliary cysts from premalignant or malignant cystic lesions is mandatory. Herein, we report a case of peribiliary cyst, which was preoperatively assumed as unilobar Caroli's diseases in healthy young patients and briefly discuss the management of the condition. PMID- 26155228 TI - Surgical treatment of bronchobiliary fistula due to radiofrequency ablation for recurrent hepatocellular carcinoma. AB - Bronchobiliary fistula (BBF) is a rare complication of radiofrequency ablation (RFA), in which there is abnormal communications between the biliary tract and the bronchial trees. Surgery should only be considered for BBF when non-invasive interventions have failed. In this report, we describe the surgical management for BBF when complicated by an abscess that was encountered after RFA in a 52 year-old woman with recurrent hepatocellular carcinoma (HCC). She had previously undergone central bisectionectomy of HCC 7 years ago, and had been treated with a sixth transarterial chemoembolization and first RFA for recurrent HCC after the operation. After the liver abscess and BBF occurred in the posterior section of the liver, she received posterior sectionectomy and hepaticojejunostomy, drainage of the lung abscess, diaphragmatic resection and repair because it was impossible to drain the abscess radiologically. Symptomatic improvements were being achieved through operative treatments where pleural effusion and pneumonic consolidation was obliterated on a 2-months follow-up image. PMID- 26155229 TI - Primary non-parasitic splenic cyst: a case report. AB - Cystic disease of the spleen is a relatively rare disease. It is classified either as a true primary cyst or as a secondary pseudocyst. Most splenic cysts are pseudocysts, which have non-epithelial lining, and are caused by previous abdominal blunt trauma. Conversely, primary splenic cysts have epithelial lining and are subdivided into parasitic and non-parasitic cyst. Non-parasitic primary splenic cyst is considered congenital and comprises about 10% of all splenic cysts. Total or partial splenectomy is the treatment of choice, but parasitic infection must be excluded prior to an operation. In this present report, we described a symptomatic, large primary non-parasitic splenic cyst, which was surgically treated with partial splenectomy. PMID- 26155230 TI - Comparison of remnant to total functional liver volume ratio and remnant to standard liver volume ratio as a predictor of postoperative liver function after liver resection. AB - BACKGROUNDS/AIMS: The future liver remnant (FLR) is usually calculated as a ratio of the remnant liver volume (RLV) to the total functional liver volume (RLV/TFLV). In liver transplantation, it is generally accepted that the ratio of the graft volume to standard liver volume (SLV) needs to be at least 30% to 40% to fit the hepatic metabolic demands of the recipient. The aim of this study was to compare RLV/TFLV versus RLV/SLV as a predictor of postoperative liver function and liver failure. METHODS: CT volumetric measurements of RLV were obtained retrospectively in 74 patients who underwent right hemihepatectomy for a malignant tumor from January 2010 to May 2013. RLV and TFLV were obtained using CT volumetry, and SLV was calculated using Yu's formula: SLV (ml)=21.585*body weight (kg)(0.732)*height (cm)(0.225). The RLV/SLV ratio was compared with the RLV/TFLV as a predictor of postoperative hepatic function. RESULTS: Postheptectomy liver failure (PHLF), morbidity, and serum total bilirubin level at postoperative day 5 (POD 5) were increased significantly in the group with the RLV/SLV <=30% compared with the group with the RLV/SLV >30% (p=0.002, p=0.004, and p<0.001, respectively). But RLV/TFLV was not correlated with PHLF and morbidity (p=1.000 and 0.798, respectively). RLV/SLV showed a stronger correlation with serum total bilirubin level than RLV/TFLV (RLV/SLV vs. RLV/TFLV, R=0.706 vs. 0.499, R(2)=0.499 vs. 0.239). CONCLUSIONS: RLV/SLV was more specific than RLV/TFLV in predicting the postoperative course after right hemihepatectomy. To determine the safe limit of hepatic resection, a larger-scaled prospective study is needed. PMID- 26155231 TI - Clinicopathological characteristics and prognostic factors in combined hepatocellular carcinoma and cholangiocarcinoma. AB - BACKGROUNDS/AIMS: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC CC) is an uncommon subtype of primary liver cancer that has rarely been reported in detail. This study was performed in order to evaluate the clinicopathological characteristics and prognostic factors of cHCC-CC in single center. METHODS: The clinicopathological features of patients diagnosed and operated with cHCC-CC at Chonbuk National Hospital between July 1998 and July 2007 were retrospectively studied by comparing them with patients with only hepatocellular carcinoma (HCC) who had undergone a hepatic resection during the same period. RESULTS: Ten out of 152 patients who had undergone a hepatic resection were diagnosed with cHCC-CC and thus included in this study (M : F=8 : 2, median age: 52+/-11.1 years). According to the parameters of the 7th American Joint Committee on Cancer T staging, there were 76 (50.0%), 44 (28.9%), 9 (5.9%), 18 (11.8%) and 5 (3.3%) patients with T stages 1, 2, 3a, 3b and 4, respectively. The overall survival period was longer in the HCC only group (68+/-40.4 months) than in the combined cHCC-CC group (23+/-40.1 months) (p<0.0001). The 5-year survival rate was 10% in the cHCC-CC group and 60% in the HCC group (p<0.0001). The disease free survival for patients with cHCC-HCC and HCC were 16+/-37.4 and 51+/-44.3 months, respectively (p<0.0001). Univariate analysis revealed that age, gender, transarterial chemoembolization (TACE), and T stage were statistically significant in terms of patient's overall survival. However, there were no significant clinicopathological factors identified by the multivariate analysis. CONCLUSIONS: Even after the hepatic resection in the HCC, the prognosis is poorer if the patient has cholangiocellular components compared to the usual HCC. PMID- 26155232 TI - Role of the 1-month protocol transarterial chemoinfusion in detecting intrahepatic metastasis after resection of large hepatocellular carcinoma greater than 10 cm. AB - BACKGROUNDS/AIMS: Tumor recurrence is very common after hepatic resection of hepatocellular carcinoma (HCC) >=10 cm. The purpose of this study was to validate the prognostic significance of the preoperative alkaline phosphatase (ALP) level and early intrahepatic metastasis in HCC patients who underwent resection of large HCC. METHODS: Clinical data of 100 large HCC patients who underwent liver resection were retrospectively reviewed. All of them underwent protocol transarterial chemoinfusion (TACI) at 1 month. RESULTS: Median tumor diameter was 13.8 cm, and 94% were single lesions. Systematic and non-systematic resections were performed in 91% and 9%, respectively, with R0 resection achieved in 84%. Overall 1-, 3- and 5-year survival rates were 76%, 38.5%, and 30.4%, respectively. Univariate analyses on patient survival revealed that intrahepatic metastasis on 1-month protocol TACI was the only significant risk factor (p=0.002). Mean ALP values according to the intrahepatic metastasis on 1-month protocol TACI were 124.6+/-76.9 IU/L and 145.1+/-92.6 IU/L, which did not show a statistical difference (p=0.23). CONCLUSIONS: In patients with large HCC, 1-month protocol TACI combined with hepatic resection may contribute to the early detection and timely treatment of potentially preexisting metastatic lesions. PMID- 26155233 TI - Cholecystectomy in octogenarians: recent 5 years' experience. AB - BACKGROUNDS/AIMS: Aging of population is leading to more operative treatments on elderly patients in various aspects. Growing numbers of patients are going through operations about cholecystitis in the same sense. We tried to survey them anew about remarkably increasing octogenarian patients and the outcome after operative management for cholecystitis seeking to improve treatment result. METHODS: For 5 years, from March 2007 to Febraury 2012, 57 octogenarian patients had cholecystectomy among total 380 cases. Patients were compared between total patients and octogenarians on perioperative follow-up findings in medical records. RESULTS: Underlying diseases were prevailing in octogenarian by more than 70% of cases. Severe acute cholecystitis was more often observed in octogenarians and procedures like endoscopic retrograde cholangiopancreaticography were more often performed preoperatively, showing more frequent conversion to open method from laparoscopic procedure. Complications such as peritonitis, sepsis, wound problem, including mortality were much more common in octogenarian cholecystectomy patients. When compared to total cholecystectomy patient group, octogenarian patients had more problems in every items significantly (p<0.05). CONCLUSIONS: High rates of complications and mortality accompanying prolonged symptoms and examinations was inevitable for octogenarian patients after cholecystectomy. Operative treatment per se appears to be inevitable, thus it should make the patients be informed about risks with more attention to every aspect of care. PMID- 26155234 TI - A model for predicting pancreatic leakage after pancreaticoduodenectomy based on the international study group of pancreatic surgery classification. AB - BACKGROUNDS/AIMS: With recent advances in pancreatic surgery, pancreaticoduodenectomy (PD) has become increasingly safe. However, pancreatic leakage is still one of the leading postoperative complications. An accurate prediction model for pancreatic leakage after PD can be helpful for pancreas surgeons. The aim of this study was to provide a new model that was simple and useful with high accuracy for predicting pancreatic leakage after PD. METHODS: To predict the occurrence of pancreatic leakage, several factors were selected using bivariate analysis and univariate logistic regression analysis. The final model was developed using multivariable logistic regression analysis in the model construction data set. RESULTS: Overall, 41 of 100 patients had pancreatic leakage by the International Study Group on Pancreatic Fistula (ISGPF) criteria. Soft pancreatic parenchyma, small pancreatic duct diameter (<=3 mm), and combined resection of SMV and portal vein were independently predictive of pancreatic leakage. The risk score (R) for individual patients can be calculated by combining the 3 prognostic values with the regression test: R=0.5986+(0.5533*pancreatic parenchyma)+(0.5448*pancreatic duct diameter)+(0.8453*combined resection). The overall predictive accuracy of the model, as measured by the receiver operating characteristic (ROC) curve, was 0.728. CONCLUSIONS: Although continued refinements and improvements in the model are needed, the present model may assist pancreatic surgeons in the prediction of pancreatic leakage after PD. PMID- 26155235 TI - Experience with partial cholecystectomy in severe cholecystitis. AB - BACKGROUNDS/AIMS: Partial cholecystectomy (PC) is often an inevitable operative procedure when Calot triangle is severely inflamed and fibrosed with conglomerated structures. We reviewed our clinical outcomes of PC to compare its feasibility with conventional total cholecystectomy (TC), especially for its possible application to laparoscopic procedure. METHODS: From Aug. 2000 to July 2008, 20 cases of PC by laparotomy were performed, including converted cases during laparoscopic cholecystectomy. Sixty-eight cases of TC by open method during the same period were compared in a mean follow-up period of 108 months. RESULTS: Bile fistula was observed in 3 cases of PC; one case needed endoscopic biliary stent for management and a second case showed fistula that closed by supportive care in 2 months. The last patient died from peritonitis. No bile fistula was observed in PC. Morbidities were found in 9 cases of PC (45%) and in 11 cases of TC (16.2%). Bile fistula (n=3) and wound infection (n=3) were prominent in the PC group, and wound infection (n=7) in the TC group. Reoperations were necessary for 5 (25.0%) and 4 (5.9%) patients from PC and TC, respectively. Mortality occurred in 2 (2/10 10%) and 4 cases (4/68 5.9%) of PC and TC, respectively. Two mortalities in each group resulted from direct extension of cholecystitis. CONCLUSIONS: Considering the higher risks of complications and mortality, PC should be avoided as long as possible, and patients should always be informed of its clinical outcomes postoperatively. Further elaboration of a safer operative plan should be sought. PMID- 26155236 TI - Cystic duct closure during partial cholecystectomy: ten years' experience. AB - BACKGROUNDS/AIMS: When surgeons face difficulties in dissecting the Calot triangle during cholecystectomy due to severe inflammation or fibrosis, the proximal portion of the gallbladder is left in place to avoid injury to the bile duct; this procedure is called partial cholecystectomy (PC), and it is associated with a much higher complication rate after the operation. METHODS: We surveyed the clinical outcomes of 25 cases of PC by laparotomy during ten years from January 1998 to December 2007, for a total of 95 months of the mean follow-up period. Patients were separated in two groups for comparison: group I (n=15), in which cystic duct closure was tried from the intraluminal cystic ductal opening; and group II (n=10), in which cystic ductal circumferential ligation was possible. RESULTS: Bile fistula occurred in 4 cases of group I, while no fistula occurred in group II. Postoperative peritonitis was observed in 4 cases from group I, with 3 of them caused by leakage of bile when the cystic duct could not be properly managed by stitches or staples. One of these peritonitis cases was fatal, but no case in group II showed peritonitis postoperatively. Wound infection, retained stone, and reoperations were also more frequent in group I, in 4, 2, and 5 cases. The mortality was 3 in group I and 1 in group II. CONCLUSIONS: When inevitable partial cholecystectomy is carried out, more attention should be focused on secure ligation of the cystic duct, with the expectation of an improved outcome of the operation on a large scale. Otherwise, patients should be clearly informed about the high risks of postoperative complications. PMID- 26155237 TI - Case report of a pancreatic squamoid cyst. AB - Squamoid cyst of the pancreas is a very rare disease and it has been proposed only recently as a distinct pathologic lesion. We herein present a case of pancreatic squamoid cyst in a patient who underwent laparoscopic resection. A 60 year-old woman had an abdominal computed tomography (CT) scan for a routine check up, and a multi-cystic lesion of 1.8-cm in size was incidentally found in the tail of the pancreas. Biochemical laboratory tests were within normal limits. At first, we presumed that the most likely diagnosis of the cystic lesion was an intraductal papillary mucinous neoplasm. To treat this lesion, we performed laparoscopic spleen-saving distal pancreatectomy. The patient showed the usual routine postoperative course and she was discharged 10 days after surgery. On examination of the resected specimen, a well-defined, oligolocular cystic mass was found in the pancreatic tail, without a solid portion. Histologic examination revealed that the cysts had linings ranging from flat squamoid cells to transitional cells with non-keratinization. After immunohistochemical staining, the final diagnosis was confirmed to be squamoid cyst of the pancreas. This lesion appears to be regarded as a benign entity, thus an extended operation should be avoided and resection of the lesion can be performed minimally. PMID- 26155238 TI - Collision tumor of the ampulla of Vater - Coexistence of neuroendocrine carcinoma and adenocarcinoma: report of a case. AB - Herein, we present a case of coexisting neuroendocrine carcinoma and conventional adenocarcinoma (collision tumor) in the ampulla of Vater, which has seldom been reported in the literature. A 51-year-old man presented with a month history of jaundice. MRCP disclosed about 1.9*1.8 cm sized heterogeneously enhancing mass in ampulla of Vater, causing obstructions of distal common bile duct. He underwent pylorus-preserving pancreaticoduodenectomy under the diagnosis on ampulla of Vater cancer. Pathologically, sections on the ampulla of Vater showed conventional ductal adenocarcinoma extended and collided with poorly differentiated neuroendocrine carcinoma. In conclusion, we hereby presented a case of coexisting neuroendocrine carcinoma and conventional adenocarcinoma in the ampulla of Vater. PMID- 26155239 TI - Clinical features and survival outcome of locally advanced extrahepatic cholangiocarcinoma. AB - BACKGROUNDS/AIMS: Little is known about clinical features and survival outcome in locally advanced unresectable extrahepatic cholangiocarcinoma (EHC). The aim was to investigate the clinical features and the survival outcome in these patients, and to evaluate the role of palliative resections in locally advanced unresectable EHC. METHODS: Between 1995 and 2007, 280 patients with locally advanced unresectable EHC were identified. Clinical, pathologic, and survival data were investigated. A comparative analysis was done between those who received palliative resection (PR) and those who were not operated on (NR). RESULTS: The overall median survival of the study population was 10+/-1 months, and the 3- and 5-year survival rates (YSR) were 8.5% and 2.5%, respectively. The median survival, 3- and 5-YSR of PR were 23 months, 32.1% and 13.1%, respectively. For NR, they were 9 months, 3.9% and 0%, which were significantly worse than PR (p<0.001). In univariate analysis, T classification, N classification, tumor location, palliative resection, adjuvant treatment, chemotherapy, and radiation therapy were factors that showed survival difference between PR and NR. Regional lymph node metastasis (RR, 2.084; 95% CI, 1.491 2.914; p<0.001), non-resections (RR, 2.270; 95% CI, 1.497-3.443; p<0.001), and no chemotherapy (RR, 1.604; 95% CI, 1.095-2.349; p=0.015) were identified as risk factors for poor outcome on multivariate analysis. CONCLUSIONS: Without evidence of systemic disease, palliative resection may provide some survival benefit in selected locally advanced unresectable EHCs and adjuvant treatment may further improve survival outcome. PMID- 26155240 TI - Analysis of gallbladder polypoid lesion size as an indication of the risk of gallbladder cancer. AB - BACKGROUNDS/AIMS: Recent advances in ultrasonography have contributed to the early detection of gallbladder cancer. We attempted to predict the progression of the disease by comparing the sizes of polypoid lesions, and we suggest that the size of the lesion would be a useful guideline to determine an appropriate primary surgical approach for polypoid lesions of the gallbladder. METHODS: We have retrospectively analyzed 253 patients that, during the operation period from January 2009 to December 2011, had had ultrasonographically detected gallbladder polypoid lesions, and who underwent cholecystectomy at Ulsan university hospital. We have analyzed the demographic data of the patients, the preoperative size of polypoid lesions, and pathologic findings. RESULTS: Of a total of 253 patients, 235 patients had benign lesions, and 18 patients had malignant lesions. Among the malignant polyp patients, 11 had pT1 cancer, 6 had pT2 cancer, and 1 had pT3 cancer. The average size of polypoid lesions was 9.1+/-3.1 mm and that of malignant lesions was 28.2+/-16.4 mm. The receiver operating characteristic (ROC) curve of the benign and malignant groups shows that 14.5 mm is the optimal point of prediction of the malignancy. Of a total of 18 patients of GB cancer, 11 had pT1 and the average size of their polypoid lesions was 20.5+/-5.8 mm 7 had pT2 with a size of 39.1+/-20.7 mm. ROC curve analysis of the pT1 and pT2 groups shows that 27 mm would be the optimal point to predict T2 and above cancer. CONCLUSIONS: In the case of an early cancer, curative treatment can be achieved through a simple and minimally invasive laparoscopic cholecystectomy. We attempted to predict early cancer occurrence among polypoid lesions of the gallbladder using the simplest standard, size. Although there are some limitations, size can be a simple and easy way to evaluate polypoid lesions of the gallbladder. PMID- 26155241 TI - Impact of critical pathway implementation on hospital stay and costs in patients undergoing pancreaticoduodenectomy. AB - BACKGROUNDS/AIMS: Recent studies have shown that pancreaticoduodenectomy (PD) can be performed quite safely. Critical pathway (CP) has been one of the key tools used to achieve excellent outcomes in high-quality, high-volume centers. This study was designed to evaluate the impact of CP implementation for PD patients. METHODS: The important components of CP for PD patients include the early start of an oral diet and removal of the abdomen drain following follow-up computed tomography, with the intention of shortening the postoperative hospital stay. The study group (CP group) comprised of 88 patients who underwent pylorus-preserving or classical PD from January 2009 to December 2010. The control group (pre-CP group) was 185 patients who underwent PD between January 2005 and December 2008. RESULTS: The two groups did not show significant differences in demographic profiles and the primary diagnosis. The incidences of overall postoperative complications such as delayed gastric emptying, fistula, and hemorrhage were similar or decreased in the CP group (54% vs. 40.9%). The incidence of clinically significant complications also showed a similar rate (5.4% vs. 4.5%) between the two groups. The nutritional status at discharge and re-admission rates were not different. The CP group showed a significantly shorter postoperative hospital stay (20.2+/-9.2 days vs. 14.9+/-5.1 days, p<0.001) and the total medical costs were also significantly reduced, by 15% (p<0.001). CONCLUSIONS: The results of this study indicated that the implementation of CP for PD patients can decrease the length of hospital stay and reduce medial costs, with maintenance or improvement of patient outcomes. Further investigation is necessary to validate the actual impact of CP for PD through multi-center high-volume studies. PMID- 26155242 TI - Preliminary results of binding pancreaticojejunostomy. AB - BACKGROUNDS/AIMS: The post-operative complications and clinical course of pancreaticoduodenectomy (PD) largely depend on the pancreaticojejunostomy (PJ). Several methods of PJ are in clinical use. We analyzed the early results of binding pancreaticojejunostomy (BPJ), a technique reported by SY Peng. METHODS: We retrospectively reviewed the clinical results of patients who received BPJ in Inha University Hospital from 2006 to 2011. 21 BPJs were performed with Peng's method. The definition of postoperative pancreatic fistula (PF) was a high amylase content (>3 times the upper normal serum value) of the drain fluid (of any measurable volume), at any time on or after the 3rd post-operative day. The pancreatic fistula was graded according to the International Study Group for Pancreatic Fistula (ISGPF) guidelines. RESULTS: Of the 21 patients who received BPJ, 11 were male. The median age was 61.2 years. PD surgery included 4 cases of Whipple's procedures and 17 cases of pylorus-preserving PD. According to the post operative course, 16 patients recovered well with no evidence of PF. A total of 5 patients (23.8%), including 3 grade A PFs and 2 grade C PFs, suffered from a pancreatic fistula. 3 patients with grade A PF recovered with conservative management. CONCLUSIONS: The BPJ appears to be a relatively safe procedure based on this preliminary study, but further study is needed to validate its safety. PMID- 26155243 TI - A comparative study regarding the effect of an intraperitoneal anti-adhesive agent application in left-liver living donors. AB - BACKGROUNDS/AIMS: After left-sided hepatectomy due to a living donor, the stomach can become adhered to the hepatic cut surface. An unwanted gastric stasis can occur. For prevention of such gastric adhesion and laparotomy-associated adhesive ileus, some anti-adhesive agents have been developed for intra-abdominal application. The purpose of this study is to evaluate the effect of an intraperitoneal anti-adhesive agent application compared with a historical control group. METHODS: The study group consisted of 220 consecutive living donors who donated a left-liver graft during the time period between January 2006 and December 2011. The anti-adhesive agent which was used was composed of sodium hyaluronate and sodium carboxymethyl cellulose. The historical control group which used no anti-adhesive agent included 220 consecutive left-liver donors during the time period between January 1998 and December 2004. RESULTS: An overt gastric stasis which required fasting was observed in 5 subjects (2.3%) in the study group and in 7 subjects (3.2%) in the control group (p=0.77). An additional work-up to determine gastric stasis or prolonged ileus was performed in 17 (7.7%) and 22 (10%) donors, respectively (p=0.51). Only one donor in the control group underwent a laparotomy for an intestinal obstruction. No clinical factors such as patient age, sex, body mass index, remnant right liver proportion, shape of skin incision, and duration of surgery were significant risk factors of gastric stasis or prolonged ileus. No harmful side-effects of the anti-adhesive agent were identified. CONCLUSIONS: As a result of this study, the application of an anti adhesive agent could not be proved as to be effective for prevention of gastric stasis and postoperative ileus. A further randomized and controlled study will be required to demonstrate the real benefits of an anti-adhesive application in left liver living donors. PMID- 26155244 TI - Non-typhoid salmonella septic arthritis in dual living liver transplant recipient: a case report. AB - Non-typhoid salmonellosis is an infectious disease caused by Salmonella species other than Salmonella typhi. Although the usual clinical course of non-typhoid salmonellosis is a benign self-limiting gastroenteritis, these bacteria are especially problematic in immunocompromised individuals, including patients with malignancies, human immunodeficiency virus, or diabetes, and those receiving corticosteroids or other immunotherapy agents. In addition to enteric symptoms, Salmonella species give rise to extra-intestinal complications, including self limiting arthritis, which appears 1 to 3 weeks after the onset of infection and lasts from a few weeks to several months. In some patients, however, this arthritis spears to be chronic in nature. We describe herein a living-donor liver transplant recipient who experienced non-typhoid Salmonella-triggered arthritis in the left hip. The patient recovered uneventfully after 6-month-long antibiotics treatment. Clinicians involved in transplantation should be aware of the possibility that transplant recipients, like other immunocompromised individuals, are at risk of salmonellosis and therefore require careful clinical and microbiological evaluation, with the goals of prevention and early recognition of infection. PMID- 26155245 TI - AFP-producing acinar cell carcinoma treated by pancreaticoduodenectomy in a patient with a previous radical subtotal gastrectomy by gastric cancer. AB - We report a case of alpha-fetoprotein (AFP)-producing acinar cell carcinoma (ACC) of the pancreas. The tumor was diagnosed in a 72 yearold female after radical subtotal gastrectomy (Billroth I) due to early gastric cancer six months before. The initial serum AFP levels were increased to 2,254.1 IU/ml and preoperative imaging studies showed a mass with approximately 2.5 cm in diameter near the neck of the pancreas. A pancreaticoduodenectomy was performed. The pathologic examination revealed an ill-defined lobulating tumor confined to the pancreas (T1 stage). Immunohistochemical study showed that the tumor cells expressed AFP. The Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) suggested that cisplatin would be more desirable than gemcitabine in AFP-producing ACC of the pancreas as an adjuvant chemotherapy. However, the adjuvant chemotherapy was not performed due to the early pathological stage. The patient died from carcinomatosis and pneumonia. Even if the tumor was on a relatively early stage, an adjuvant treatment should be considered ACC. PMID- 26155246 TI - Systemic capillary leak syndrome (Clarkson's disease) during elective pylorus preserving pancreaticoduodenectomy: case report. AB - Systemic capillary leak syndrome (SCLS), also called Clarkson's disease is rare and life-threatening disorder of unknown etiology, which is a characteristic triad of hypovolemic shock, hemoconcentration, and hypoalbuminemia. Unexplained capillary leakage from the intravascular to the interstitial space, which has been estimated up to 70% of the intravascular volume, is the proposed mechanism. Because the pathogenesis is unknown, it is diagnosed clinically after exclusion of other diseases that cause systemic capillary leak and no efficacious pharmacological treatment has been clearly established. The mortality rate ranges from 30% to 76%. In Korea, four cases of SCLS (5 cases in adult and 1 case in child) were reported by 2012. We describe a case of severe SCLS that suddenly occurred and rapidly progressed during pylorus preserving pancreaticoduodenectomy and review the literature. PMID- 26155247 TI - Assessment of right liver graft perfusion effectiveness between one and two catheter infusion methods. AB - BACKGROUNDS/AIMS: Conventional graft perfusion method using one small-caliber catheter takes a relatively long time for right liver graft perfusion, thus some modification is needed. In this study, we intended to assess the effectiveness of right liver graft perfusion methods through comparison of different infusion catheters. METHODS: The study consisted of two parts including one bench experiment to obtain data of hydraulic infusion and one clinical trial of 40 cases on graft perfusion with one- versus two-catheter infusion methods. These two graft infusion methods were compared in terms of the perfusion time and washing-out efficiency. RESULTS: At bench experiment, the infusion flow rate and infusion pressure were 3.3 ml/sec and 1.9 cmH20 in one blood transfusion catheter group, and 11.7 ml/sec and 3.1 cmH20 in single transurethral resection of prostate irrigation catheter group, and 6.6 ml/sec and 2.0 cmH20 in two blood transfusion catheters group, respectively. In clinical trial with 40 right liver grafts, two-catheter group had a shorter graft portal perfusion time for the first 2 L of histidine-tryptophan-ketoglutarate (HTK) solution than the conventional one-catheter group (375+/-25 seconds vs. 662+/-34 seconds; p=0.001) and a lower rate of incomplete blood washing-out after the initial 2 L portal perfusion (40% vs. 85%; p=0.03). CONCLUSIONS: The two-catheter infusion method appears to be more effective than the conventional one-catheter infusion method for right liver graft perfusion at the back table. Large size of right liver grafts seems to be its good indication. PMID- 26155248 TI - Tailored long-term immunosuppressive regimen for adult liver transplant recipients with hepatocellular carcinoma. AB - BACKGROUNDS/AIMS: There are few guidelines for tailored immunosuppressive regimens for liver transplantation (LT) recipients with hepatocellular carcinoma (HCC). To establish long-term immunosuppressive regimens suitable for Korean adult LT recipients, we analyzed those that were currently in use at a single high-volume institution. METHODS: This cross-sectional study comprises three parts including review of the immunosuppressive regimens used to manage 2,147 adult LT outpatients, review of LT recipients who were diagnosed of HCC at LT, and review of LT recipients who suffered from HCC recurrence. RESULTS: In 1,000 adult LT recipients who were living more than 5 years with no adverse events, 916 received a calcineurin inhibitor (CNI)-based therapy (CNI only in 520; CNI with mycophenolate mofetil [MMF] in 396) and 84 were receiving an MMF-based therapy (MMF only in 45; MMF with minimal CNI in 39). Tacrolimus was preferred over cyclosporine for both monotherapy and combination therapy along the passage of posttransplant period. There was no difference in selection of immunosuppressants, target blood concentration, and rate of combination therapy between LT recipients with and without HCC, except for the first 1 year. Sirolimus-based regimens were applied in 21 patients who showed HCC recurrence. Sorafenib was often used after conversion to sirolimus. CONCLUSIONS: Tailored immunosuppressive regimen covering the long-term posttransplant period should be established after consideration of individualized patient profiles including HCC. PMID- 26155249 TI - A survey of attitudes to clinical practice guidelines in general and adherence of the Korea practical guidelines for management of gallbladder polyp: a survey among private clinicians in Korea. AB - BACKGROUNDS/AIMS: While clinical practice guidelines are effective tools for improving the quality of patient care and provide specific recommendations for daily practice, the usage of them have been often suboptimal. Therefore, evaluation of physician attitude to guidelines is an important initial step in improving guideline adherence levels. The aim of this study was to survey the attitude on general guidelines and adherence with the Korea Practical Guidelines for gallbladder (GB) polyp two year after their publication and distribution among Korean private clinicians. METHODS: To evaluate the survey, questionnaires were sent with a stamp on an addressed envelope to 3,256 private clinicians who were registered at the Seoul Medical Association in April, 2010. From the 3,256 questionnaires, 376 clinicians (11.5%) responded to the survey. RESULTS: A total of 91.0% responders agreed to the statement that general guidelines were useful tools for improving patient care and quality of care. One hundred one responders (26.9%) stated that they were aware of the Korea GB polyp guidelines while 73 physicians (72.3%) founded the guideline had changed their practice and user friendly. Most of physicians (73.4%) agreed to practical procedures recommended by guidelines. CONCLUSIONS: Korean primary physicians were generally positive to the practical guidelines, as propagation of the guideline among primary physicians may improve adherence to guideline and patients care for GB polyps. PMID- 26155250 TI - Giant pedunculated hepatocellular carcinoma masquerading as a pelvic mass: a case report. AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with high frequency rates in Asia. Many of the patients have unresectable disease at the time of diagnosis, and early detection and surgical resection is the best hope for survival. But, if HCC is presenting as an extrahepatic mass, the diagnosis is difficult. Herein, we report a case of primary HCC masquerading as a pelvic mass. A 74-year-old woman was admitted to our hospital due to a palpable mass in the lower abdomen. CT scan detected an approximately 15.0*13.4*11.4 cm-sized multilobulated homogeneous enhancing mass in the right adnexa. Operative findings showed that the pelvic mass originated from the liver. We performed hepatic wedge resection. Permanent histopathologic report revealed primary HCC. Exophytic-growing hepatocellular carcinoma should be carefully diagnosed. PMID- 26155251 TI - Metastatic cholangiocarcinoma as a cause of appendicitis: a case report and literature review. AB - Metastatic carcinoma that causes appendicitis is extremely rare. To our knowledge, metastatic cholangiocarcinoma in the appendix has been reported in only 1 case in the English literature. We report herein the case of an 87-year old woman who presented with abdominal pain and jaundice. Advanced cholangiocellular carcinoma and a proximal appendiceal mass with appendicitis were detected on contrast-enhanced computed tomography and positron emission tomography/computed tomography. After elective laparoscopic appendectomy and wedge resection of the cecum, pathologic results revealed metastatic adenocarcinoma from extrahepatic cholangiocellular carcinoma in the appendix. PMID- 26155252 TI - Fatal liver injury complicated by percutaneous catheter drainage after distal pancreatosplenectomy in a patient with pancreatic cancer. AB - Postoperative pancreatic fistula (POPF) combined with postoperative fluid collection, bleeding and abscess formation is one of the most critical morbidities after distal pancreatectomy or pancreaticoduodenectomy. Percutaneous catheter drainage has been commonly used for managing for the postoperative management of abnormal fluid collection. Removal of the catheter is rarely associated with occurrence of life-threatening complication such as serious liver damage. Herein, we report a case of unexpected fatal liver injury complicated by percutaneous catheter drainage treatment after distal pancreatosplenectomy in a patient with pancreatic cancer. We suggest that prudent decision for timing of catheter removal and meticulous care during procedure can reduce the possibility of major liver injury in patients with percutaneous transhepatic catheter drainage. PMID- 26155253 TI - Recent classifications of the common bile duct injury. AB - Laparoscopic cholecystectomy is now a gold standard treatment modality for gallstone diseases. However, the incidence rate of bile duct injury has not been changed for many years. From initial classification published by Bismuth, there have been many classifications of common bile duct injury. The initial classification, levels and types of bile duct injury, and currently combined vascular injuries are reviewed here. PMID- 26155254 TI - Surveillance method and imaging characteristics of recurrent biliary cancer after surgical resection. AB - This is a review of the diagnostic imaging techniques and findings of recurrent biliary cancer after surgical resection of the extrahepatic bile duct and gallbladder. Radiological examination plays an important role in diagnosing postoperative recurrence of biliary cancers. Early detection and diagnosis of recurrent cancer is critical in obtaining proper treatment and improves the prognosis. In the surveillance of recurrent biliary cancer, several diagnostic imaging modalities are currently used. Usually CT is the most common method for surveillance of postoperative patients, but MRI and PET/CT scans are also widely used. Recurrent biliary cancer can manifest as local recurrence, liver metastasis, lymph node metastasis, and peritoneal metastasis. Imaging findings of a locally recurrent tumor or metastatic lymph node enlargement overlaps with benign postoperative changes, thus radiologists commonly overlook subtle CT findings or misinterpret them as benign postoperative changes. There are several reports that FDG-PET scan is more effective in the diagnosis of recurrent biliary tract cancer than CT. Multidisciplinary diagnostic approaches using CT, MRI, and FDG-PET as well as clinical information seem to be essential for the precise diagnosis of recurrent tumors. PMID- 26155255 TI - Extended distal pancreatectomy for advanced pancreatic neck cancer. AB - BACKGROUNDS/AIMS: We investigated the clinical application of extended distal pancreatectomy in patients with pancreatic neck cancer accompanied by distal pancreatic atrophy. In this study, we have emphasized on the technical aspects of using the linear stapling device for a bulky target organ. METHODS: From March 2010 to September 2013, 46 patients with pancreatic adenocarcinoma, who underwent pancreatic resection with radical intent at our institute, were reviewed retrospectively. Among them, three patients (6.5%) underwent extended distal pancreatectomy. A linear stapling device and vise-grip locking pliers were used for en bloc resection of the distal pancreas, first duodenal portion, and distal common bile duct. The results were compared with those after standard pancreatectomy. RESULTS: All three patients presented with jaundice, and the ratio of pancreatic duct to parenchymal thickness of the pancreatic body was greater than 0.5. Grade A pancreatic fistula developed in all of the cases, but none of these fistulae were lethal. Pathological staging was T3N1M0 in all of the patients. The postoperative daily serum glucose fluctuations and insulin requirements were comparable to those in patients who received pancreaticoduodenectomy or distal pancreatectomy. At the last follow-up, two patients were alive with liver metastasis at 4 and 10 months postoperatively, respectively, and one patient died of liver metastasis at 5 months postoperatively. CONCLUSIONS: While the prognosis of advanced pancreatic neck adenocarcinoma is still dismal, extended distal pancreatectomy is a valid treatment option, especially when there is atrophy of the distal pancreas. Also, the procedure is technically feasible, and further refinement is necessary to improve patient survival. PMID- 26155256 TI - Clinical feasibility and nutritional effects of early oral feeding after pancreaticoduodenectomy. AB - BACKGROUNDS/AIMS: Pancreaticoduodenctomy (PD) is associated with high rates of postoperative morbidity and mortality. Although many studies have shown that early postoperative enteral nutrition improves postoperative outcomes, limited clinical information is available on postoperative early oral feeding (EOF) after PD. The aim of this study was to evaluate the clinical feasibility, safety, and nutritional effects of EOF after PD. METHODS: Clinical outcomes were investigated in 131 patients who underwent PD between 2003 and 2013, including 81 whose oral feeding was commenced within 48 hours (EOF group) and 50 whose oral feeding was commenced after resumption of bowel movements (traditional oral feeding [TOF] group). Postoperative complications, energy intake, and length of stay (LOS) were reviewed. RESULTS: Demographic factors were similar in the two groups. The EOF group had a significantly shorter LOS (25.9+/-8.5 days vs. 32.3+/-16.3 days; p=0.01) than the TOF group. The rates of anastomotic leak (1.2% vs. 16%, p=0.00) and reoperation (3.7% vs. 20%, p=0.01) were significantly lower in the EOF group. In the clinically acute phase from postoperative day 1 to day 5, the mean daily calorie intake (847.0 kcal vs. 745.6 kcal; p=0.04) and mean daily protein intake (42.2 g vs. 31.9 g; p=0.00) in the EOF group were significantly higher than that in the TOF group. CONCLUSIONS: Postoperative EOF is a clinically safe, feasible, and effective method of nutritional support after PD. PMID- 26155257 TI - Does international study group on pancreatic fistula (ISGPF) classification need modification after distal pancreatectomy? AB - BACKGROUNDS/AIMS: Few reports have validated the clinical postoperative pancreatic fistula (PF) after distal pancreatectomy. The study intended to validate the predictability for clinical PF of drain amylase and lipase and to find out more appropriate postoperative day (POD) for diagnostic criterion of PF. METHODS: A total of 154 patients underwent distal pancreatectomy. We used the clinical database registry system of the Gangnam Severance Hospital and Severance Hospital, Yonsei University Health System for these analyses. The receiver operating characteristic curve of the drain amylase or lipase concentration on each day was used to predict clinical PF (International Study Group on Pancreatic Fistula [ISGPF] grade B or C) and areas under the curves (AUC) were compared. RESULTS: Amylase and lipase AUC values poorly predicted clinical PF before POD 3 and, gradually increased until POD 5 and became well correlated with clinical PF (ISGPF grade B or C). In contrast, the prediction of clinical PF using drain lipase did not differ from that using drain amylase. The drain amylase concentration on POD 6 was most precisely correlated with clinical PF. CONCLUSIONS: Clinical PF prediction was validated by using drain amylase and lipase concentrations, in which drain amylase assessment at POD 6 appeared to be an appropriate diagnostic criterion of PF after distal pancreatectomy. We suggest some modification of ISGPF definition, especially for distal pancreatectomy. PMID- 26155258 TI - Deceased donor liver transplantation performed one week after small bowel resection for complicated umbilical hernia: a case report. AB - Emergent abdominal surgery in cirrhotic patients with ascites can result in dismal postoperative outcomes such as sepsis and hepatic failure. In the present case, small bowel resection followed by anastomosis by the hand-sewn method was performed for small bowel strangulation caused by an umbilical hernia; deceased donor liver transplantation was performed one week after the bowel resection because of deterioration of hepatic function. To the best of our knowledge, this is the first case of liver transplantation performed at only one week after small bowel resection; and although we obtained a good result, the optimal time to perform liver transplantation in this situation requires further evaluation. PMID- 26155259 TI - Management of inferior vena cava thrombosis after blunt liver injury. AB - Inferior vena cava (IVC) thrombosis after traumatic liver injury is an extremely rare condition, and only 12 cases have been reported in the English literature since 1911. We report a case of a 26-year-old man who presented with IVC thrombosis after blunt liver injury. IVC thrombosis was incidentally detected by computed tomography 15 days after conservative management of blunt liver injury. The patient denied any symptoms of thrombophlebitis and did not have any evidence of hypercoagulable state. We placed an IVC filter via the right jugular vein and started the anticoagulation treatment. The patient recovered successfully without operative treatment and IVC thrombosis disappeared completely two months later. We suggest that that the possibility of IVC thrombosis should be considered in patients with a large hematoma of the liver, which may cause compression of the IVC. PMID- 26155260 TI - Superior mesenteric vein thrombosis accompanied with severe appendicitis. AB - Superior mesenteric vein (SMV) thrombosis caused by acute appendicitis is a very rare entity nowadays. We report a successfully treated case of a 21-year-old man with SMV thrombosis associated with severe acute appendicitis. Intravenous heparin was administered, and it was later substituted with warfarin. Systemic antibiotic therapy was continued for 1 week, and it was substituted with oral antibiotics, which were administered for 3 weeks. On the 45th postoperative day, follow-up computed tomography scan demonstrated dissolution of SMV thrombosis. Anticoagulation therapy was maintained for 3 months. He was discharged without any complications. SMV thrombosis can be treated successfully with emergency appendectomy, broad-spectrum antibiotics, and anticoagulation therapy. PMID- 26155261 TI - Influence of metabolic and other clinicopathologic factors on the prognosis of patients with hepatocellular carcinoma undergoing hepatic resection. AB - BACKGROUNDS/AIMS: The prognosis of hepatic resection for hepatocellular carcinoma (HCC) in patients with cirrhosis is worse than in those without cirrhosis. In Korea, the hepatitis B virus prevalence rate is higher than in other countries. Therefore, we investigated patients' clinicopathologic and metabolic factors that affect the postoperative outcomes of hepatic resection for HCC in our hospital in Korea. METHODS: From August 2000 to December 2012, 171 HCC patients underwent hepatic resections at our institution. Two operative mortality cases and two short-term follow up cases were excluded. Data was collected from a retrospective chart review. There were 133 males (79.6%) and 34 females (20.3%), with a mean age of 58.2+/-10.2 years (range, 22-81 years), and the relationship between clinicopathologic and metabolic factors and the prognosis of patients with HCC undergoing hepatic resection were evaluated by univariate and multivariate analysis. RESULTS: Hypertension, major surgery, perioperative transfusion, resection with radiofrequency ablation (RFA) or cryoablation, and resection margin were risk factors for overall survival, and hypertension, albumin, resection with RFA or cryoablation, perioperative transfusion, and tumor size were risk factors for disease-free survival. CONCLUSIONS: We found that hypertension, perioperative transfusion, and resection with RFA or cryoablation were risk factors for both disease-free and overall survival after hepatic resection in HCC patients. Further study is required to clarify the influence of metabolic and other clinicopathologic factors on the prognosis of HCC. PMID- 26155262 TI - Experience of laparoscopic liver resection for various liver diseases. AB - BACKGROUNDS/AIMS: We present our experience of laparoscopic liver resection for various liver diseases. METHODS: From April 2008 to August 2012 in Chungnam National University, 68 of 253 liver resections were performed laparoscopically. During the first year, laparoscopy-assisted liver resection was mainly performed and subsequently totally laparoscopic liver resection was the main operative type. Surgery type for treatment purposes was decided preoperatively. Clinical data were collected retrospectively and analyzed. RESULTS: Preoperatively, 43 patients (63.2%) were diagnosed with benign disease, 19 patients (27.9%) were malignant liver tumors and 6 patients (8.8%) were indeterminate liver tumor but favorable towards malignancy. Anatomical major liver resection was performed in 58 cases (85.3%) and 10 cases (14.7%) were non-anatomical resection. Left hemihepatectomy was performed in 38 cases (55.8%) followed by left lateral sectionectomy in 18 cases (26.5%), and segment IV and IVa segmentectomy, were each in 1 case. Mean operation time was 235.0 minutes (range, 60-470) and 14 patients (18.6%) had intraoperative transfusion. Mean postoperative hospital stay was 10.2 days (range, 4-32). Mean operation time of laparoscopy-assisted left lobectomy was 317 minutes and totally laparoscopic left lobectomy was 281 minutes, but there was no significant statistical difference between these two operation types. There were 11 episodes of postoperative complications in 8 patients. There was no mortality after laparoscopic liver resection. CONCLUSIONS: We concluded that laparoscopic liver resection is a feasible operation, but needs to be carefully conducted in malignant tumors. PMID- 26155263 TI - Feasibility of laparoscopic liver resection for giant hemangioma of greater than 6 cm in diameter. AB - BACKGROUNDS/AIMS: Liver hemangioma, the most common benign liver tumor, can be safely managed by clinical observation. However, surgical treatment should be considered in a subset of patients with giant hemangioma with abdominal symptoms. We reviewed the feasibility of total laparoscopic liver resection for giant hemangioma of >6 cm in diameter. METHODS: Nine consecutive patients who underwent total laparoscopic liver resection for giant hemangioma between August 2008 to December 2012 were included in this study. Medical records were retrospectively reviewed for demographic data, laboratory findings, and perioperative results. RESULTS: The median age of patients was 36 yrs (range, 31-63). Eight females and 1 male were included in the study. The median size of hemangioma was 11 cm in diameter (range, 6-18) and 5 patients had a hemangioma >10 cm. Indications for surgical treatments were abdominal symptoms in 4 patients, increased size in 5 patients, and uncertain diagnosis in 1 patient. The median operation time was 522 minutes for right hepatectomy, 220 minutes for left lateral sectionectomy, and 90 minutes for wedge resection. The median estimated blood loss was 400 ml (range, 50-900). There was no postoperative morbidity, including Clanvien-Dindo grade I. CONCLUSIONS: The resection of giant hemangioma demands meticulous surgical technique due to high vascularity and the concomitant risk of intraoperative hemorrhage. Laparoscopic liver resection is feasible with minimal operative complication. Therefore, laparoscopic liver resection can be considered as an option for surgical treatment for giant hemangioma. PMID- 26155264 TI - Comparative analysis of Laparoscopic versus open surgical radiofrequency ablation for malignant liver tumors. AB - BACKGROUNDS/AIMS: This study aims to evaluate the comparative effectiveness of two surgical approaches on the treatment outcomes of radiofrequency ablation (RFA) for malignant liver tumors. METHODS: Fifty-seven patients with malignant liver tumors, hepatocellular carcinoma, cholangiocarcinoma and liver metastases, who were candidates for RFA, underwent laparoscopic or open surgical treatments. RESULTS: The patients' characteristics were comparable in the two groups that received open (n=33, 57.9%) and laparoscopic (n=24, 42.1%) surgical treatments. There were no statistically significant differences between the two groups in terms of recurrence rate (p=0.337) and overall survival (p=0.423). However, patients in the laparoscopic RFA group had significantly shorter hospital stay (14.1 vs. 5.9 days, p<0.05) and experienced fewer complications (Grade I: 62.5% vs. 26.3%, p=0.102). CONCLUSIONS: Laparoscopic RFA can be performed for malignant liver tumors with lower morbidity rates, less invasiveness and lower expense compared to open surgical approach. PMID- 26155265 TI - Surgical outcome and prognostic factors in patients with gallbladder carcinoma. AB - BACKGROUNDS/AIMS: Gallbladder carcinoma is usually associated with an unfavorable prognosis, and the clinical outcome has not improved much. This study was conducted to evaluate outcomes with gallbladder carcinoma according to the type of surgery performed, and the prognostic factors for survival. METHODS: One hundred and six patients with gallbladder carcinoma, who underwent surgery for the purpose of curative resection between January 1999 and June 2012 were reviewed retrospectively. RESULTS: Out of 106 patients, curative resection was achieved in 75 (70.8%). The cumulative 1-, 2- and 5-year survival rates of the gallbladder carcinoma patients were 93.4%, 80.9% and 63.0%, respectively. Radical resections, including extended cholecystectomy, were more beneficial for long term survival of patients. The 5-year survival rate in patients who underwent curative resection (56.9%) was significantly higher than in those who underwent palliative resection (0%, p=0.000). Multivariate analysis revealed that curative resection, preoperative CA19-9, T-stage, N-stage and differentiation of histology were independently significant prognostic factors. CONCLUSIONS: Curative resection and early detection of patients with gallbladder carcinoma were the most important factors for long term survival. Radical resection improves survival for patients with localized gallbladder carcinoma and can help to access exact prognosis and treatments. PMID- 26155266 TI - Prognostic factors associated with early mortality after surgical resection for pancreatic adenocarcinoma. AB - BACKGROUNDS/AIMS: Identifying pancreatic cancer patients at high risk of early mortality following surgical resection for pancreatic cancer is important to make optimal treatment decisions in multidisciplinary setting. The purpose of this study was to identify the factors related to early mortality in patients who underwent pancreatic resection for pancreatic adenocarcinoma. METHODS: We reviewed our institution's experience with all consecutive patients who underwent pancreatectomy for pancreatic adenocarcinoma from January 2000 to December 2010. One thousand patients were eligible for our study. Fifty-three patients who did not meet the study criteria were excluded. Based on 12 months after surgery, patients were divided into early mortality group or the remaining group. We performed logistic regression analysis to identify predictors of early mortality. RESULTS: Among 947 patients who met our study criteria, 302 (31.9%) early mortality (defined as experiencing death within 12 months after surgery) occurred. Multivariate analysis revealed that patient age and surgery time period were statistically significant predictors of early mortality within six months after surgery. Poorly differentiated tumor and adjuvant chemotherapy were statistically significant predictors of early mortality within 12 months after surgery. Total pancreatectomy and lymphovascular invasion were significant (p<0.05) prognostic factors of early mortality within 6 or 12 months after surgery. CONCLUSIONS: We suggest followings to avoid early mortality after pancreatic resection: patients with multiple risk factors related to early mortality after pancreatectomy should be considered for alternative treatment; patient's general condition and surgical technique improvement are important; and adjuvant therapy should be taken into consideration. PMID- 26155267 TI - Outcomes of pancreaticoduodenectomy in patients with metastatic cancer. AB - BACKGROUNDS/AIMS: Metastatic cancer of pancreas is rarely resectable. Pancreaticoduodenectomy carries high risks of morbidities and mortalities that it is rarely performed for metastatic cancer. In this study, the clinical features and outcomes of metastatic cancer of pancreas after pancreaticoduodenectomy were reviewed and analyzed. METHODS: We retrospectively reviewed patients who underwent pancreaticoduodectomy from January 2000 to December 2012 in Samsung Medical Center. A total of 1045 patients were enrolled in this study. Inclusion criteria were patients who had metachronous lesions with tumors histologically confirmed as metastatic cancer. However, patients with tumors directly invaded pancreas head, bile duct, and duodenum were excluded from this study. Finally, a total of 12 patients who underwent pancreaticoduodenectomy due to metastatic cancer were used in this study. Clinicopathologic features and perioperative data of these 12 patients were retrospectively reviewed. RESULTS: The 12 patients included 6 females and 6 males who had metastatic lesions at pancreas head, duodenum 2nd-3rd portion, and distal common bile duct. The mean age of patients was 62.7 years old at the time of pancreaticoduodenectomy. The interval between the time of the first operation for primary cancer and pancreaticoduodenectomy was 67.7 months. The mean survival time after pancreaticoduodectomy was 38.6 months (range, 12 to 119 months). There was no fatal complication after the surgery. CONCLUSIONS: Pancreaticoduodenectomy is becoming a safer procedure with less complication compared to the past. Patients with recurrent metastatic cancer should be considered for metastectomy if tumors are resectable. Pancreaticoduodenectomy should be considered as one main treatment for patients with recurrent metastatic cancer to offer a chance of long-term survival in selected patients. PMID- 26155268 TI - Surgical outcomes of multifocal branch duct intraductal papillary mucinous neoplasms of pancreas. AB - BACKGROUNDS/AIMS: Appropriate management for multifocal branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas is still controversial. This study was intended to reveal surgical outcomes of surgical resection for multifocal BD-IPMNs, with BD-IPMNs in the remnant pancreas. METHODS: Between January 1995 and December 2013, 699 patients underwent the pancreatic resection due to IPMN of pancreas in our institution. Among them, 37 patients showed multifocal BD-IPMNs. After excluding patients who had BD-IPMNs completely resected, medical records of 22 patients with remained BD-IPMNs in the remnant pancreas were retrospectively reviewed. RESULTS: Mean patient age was 65+/-6.4 years. Types of surgery included central pancreatectomy (n=1), distal pancreatectomy (n=14), and standard pylorus-preserving pancreaticoduodenectomy (n=7). Specimen pathology showed that IPMN was either at low/intermediate-grade dysplasia (n=17) or at high-grade dysplasia (n=2). Three patients had IPMN associated with invasive carcinoma. Their mean follow-up period was 40.4 months. During follow-up, one mortality occurred 35.2 months after the operation which was not associated with IPMN. There was no clinically significant disease progression or recurrence of IPMN in the remnant pancreas during the follow-up period. CONCLUSIONS: Our results support that we can safely preserve the pancreas parenchyma with multifocal BD-IPMNs. Benign-looking multifocal BD-IPMNs in the remnant pancreas do not affect the survival of patients. PMID- 26155269 TI - An interim safety analysis of hepatocellular carcinoma patients administrating oral vitamin K with or without sorafenib. AB - BACKGROUNDS/AIMS: Vitamin K may plays a role in controlling hepatocellular carcinoma (HCC) cell growth. In this study, we intended to present 5-year experience of 72 patients receiving oral vitamin K with or without sorafenib. Its end-point was to evaluate the safety of combination therapy using sorafenib and vitamin K. METHODS: An interim analysis was performed as a single-arm cross sectional study, including 72 HCC patients who underwent liver resection or transplantation and administered oral vitamin K2 alone (n=47) or with sorafenib (n=25). RESULTS: In all patients, administration of vitamin K2 analog 45 mg/day did not show any noticeable adverse side-effect during vitamin K therapy of 23.3+/-10.6 months, except for one patient who experienced skin rash at the third day of vitamin K therapy. In 25 patients receiving sorafenib and vitamin K for 6 months or longer, any noticeable adverse side-effect suspected of vitamin K origin was not identified yet. A small proportion of patients showed unexpectedly favorable anti-tumor effects after use of vitamin K with or without sorafenib. CONCLUSIONS: Because add-on of oral vitamin K did not increase the adverse side effects of sorafenib, a combination therapy with these two agents appears to be worthy of further clinical trial with an expectation of synergistic therapeutic effects. PMID- 26155270 TI - Gallbladder perforation: a single center experience of 32 cases. AB - BACKGROUNDS/AIMS: Gallbladder perforation is a rare but potentially fatal disease. We herein present our clinical experience in diagnosis and management of 32 cases of gallbladder perforation. METHODS: This retrospective study was conducted with inclusion of all cases of gallbladder perforation that presented to our hospital from January 2012 to November 2014. Cases of traumatic gallbladder perforation and patients younger than 12 years of age were excluded from this study. RESULTS: This study included 32 patients (13 males and 19 females). The mean age of patients was 55.9 years. Gallbladder perforation was most common in the 5th and 6th decade of life. The mean age of patients with type I, II, and III gallbladder perforation was 57.0 years, 57.6 years, and 49.8 years, respectively. The most common site of perforation was the fundus, followed by the body and Hartmann's pouch (24 : 5 : 2). Most of the type I gallbladder perforations were diagnosed intraoperatively, type II gallbladder perforations were diagnosed by enhanced abdominal computed tomography, and type III gallbladder perforations were diagnosed during laparoscopic cholecystectomy converted to open cholecystectomy for cholelithiasis. Mortality was highest in patients with type I gallbladder perforation. The mean hospital stay was 10.1 days, 6.4 days, and 9.2 days in patients with type I, II, and III gallbladder perforation, respectively. The histopathologic analysis in 28 patients who were operated on showed acute cholecystitis in 19 cases, acute-on-chronic cholecystitis in 4 cases, chronic cholecystitis in 4 cases, and mucinous adenocarcinoma of the gallbladder in a single case. CONCLUSIONS: Gallbladder perforation represents a special diagnostic and surgical challenge. Appropriate classification and management are essential. PMID- 26155271 TI - Survival analysis following resection of AJCC stage III gallbladder carcinoma based on different combinations of T and N stages. AB - BACKGROUNDS/AIMS: According to 7th AJCC TNM staging system, gallbladder carcinoma (GBC) with lymph node (LN) metastasis is classified as N1 or N2; thus making the stage IIIB (N1) or IVB (N2). Stage IIIB consists of N1 status with wide coverage of T1-3, but T3N1 group often showed poorer outcomes than T1-2N1 groups. This study intended to assess post-resection prognosis of T3N1 versus other stage III subgroups. METHODS: We selected 103 patients from our institutional database of GBC who underwent R0 resection between July 1996 and June 2009 and whose GBC was confined to stage T3N0, T1-3N1 or T1-3N2. These patients were stratified into five groups, namely, T3N0 (n=26), T1N1 (n=13), T2N1 (n=35), T3N1 (n=20) and T1 3N2 (n=9), and were followed for >=5 years or until death. RESULTS: Surgical procedures were minor liver resection (n=53), minor liver resection with bile duct resection (n=23), major liver resection (n=12), major liver resection with bile duct resection (n=5), and hepatopancreatoduodenectomy (n=12). Mean follow-up period was 57.2+/-68.5 months. Overall 5-year survival rate based on all-cause death and cancer-associated death, respectively, was 57.7% and 60.6% in T3N0, 15.4% and 15.4% in T1N1 (n=13), 28.6% and 28.6% in T2N1 (n=35), 5.0% and 5.7% in T3N1 (n=20), and 22.2% and 22.2% in T1-3N2. The survival outcome of T3N1 group was the poorest among the four stage III groups and was comparable to that of stage IVB (p=0.53). CONCLUSIONS: The prognosis of T3N1 GBC is unusually poor even after R0 resection, thus we suggest extensive LN dissection may be necessary in patients with T3 tumors for accurate prognostic evaluation and radical removal of potential nodal micrometastasis. Further validation of this result is necessary in large patient populations from multiple centers. PMID- 26155272 TI - Therapeutic effect of trans-drain administration of antibiotics in patients showing intractable pancreatic leak-associated pus drainage after pancreaticoduodenectomy. AB - BACKGROUNDS/AIMS: To cope with intractable pus drainage from persistent pancreatic leak after pancreaticoduodenectomy (PD), we have empirically performed local administration of high-concentration antibiotics cocktail solution into abdominal drains. The purpose of this study was to assess its therapeutic effect in patients showing intractable pus drainage after PD. METHODS: The study group was 10 patients who underwent trans-drain administration of high-concentration antibiotics cocktail solution. Another 10 patients were selected through propensity score matching for the control group. Their medical records were retrospectively reviewed with focus on comparison of pancreatic fistula (PF) associated clinical sequences. RESULTS: Postoperative PF of grade B and C occurred in 7 and 3 patients in the study group and 9 and 1 patient in the control group, respectively (p=0.58). In the study group, a mean of 1.8 sessions of antibiotics cocktail solution (imipenem 500 mg and vancomycin 500 mg dissolved in 20 ml of normal saline) was administered. Two patients showed procedure associated febrile episodes that were spontaneously controlled within 48 hours. At 2-4 days after the first-session of antibiotics administration, pus-like drain discharge turned to be serous with significantly decreased amount. The study group showed shortened postoperative hospital stay comparing to the control group (25.2+/-4.6 vs. 31.8+/-5.6 days, p=0.011). In both groups, no patient received radiological or surgical intervention due to PF-associated complications. CONCLUSIONS: The results of our study demonstrated that trans-drain administration of antibiotics could be an effective therapeutic option for pancreaticojejunostomy leak-associated infection. Further validation of our result is necessary in large patient populations from multiple centers. PMID- 26155273 TI - Pneumatosis intestinalis after adult living donor liver transplantation: report of three cases and collective literature review. AB - BACKGROUNDS/AIMS: Pneumatosis intestinalis (PI) is a condition in which multiple gas-filled mural cysts develop in the gastrointestinal tract. Although its exact etiology remains obscure, PI is rarely observed in liver transplant (LT) recipients. METHODS: In 317 cases of adult living donor LT (LDLT) performed during 2011, PI developed in three patients during the 3 year follow-up. RESULTS: Of these three patients, the two who demonstrated PI at 6 weeks and 2 months after LT, respectively, were asymptomatic and showed no signs of secondary complications. Diagnosis was made incidentally using abdominal radiographs and computed tomography (CT) scans. PI was identified in the right ascending colon with concomitant pneumoperitoneum. These two patients received supportive care and maintained a regular diet. Follow-up CT scans demonstrated spontaneous resolution of PI with no complications. The third patient was admitted to the emergency room 30 months after LDLT. His symptoms included poor oral intake and intermittent abdominal pain with no passage of gas. Abdominal radiography and CT scans demonstrated PI in the entire small bowel, with small bowel dilatation, pneumoperitoneum, and pneumoretroperitoneum, but no peritonitis. Physical examination revealed abdominal distension but no tenderness or rebound tenderness. After 1 week of conservative treatment, including bowel rest and antibiotics therapy, PI and pneumoperitoneum resolved spontaneously without complications. CONCLUSIONS: We suggest that adult LDLT recipients who develop asymptomatic or symptomatic PI with no signs of secondary complications can be successfully managed with conservative treatment. PMID- 26155274 TI - Customized left-sided hepatectomy and bile duct resection for perihilar cholangiocarcinoma in a patient with left-sided gallbladder and multiple combined anomalies. AB - Left-sided gallbladder (LSGB) is a rare anomaly, but it is often associated with multiple combined variations of the liver anatomy. We present the case of a patient with LSGB who underwent successful resection of perihilar cholangiocarcinoma. The patient was a 67-year-old male who presented with upper abdominal pain and obstructive jaundice. Initial imaging studies led to the diagnosis of Bismuth-Corlette type IIIB perihilar cholangiocarcinoma. Due to the unique location of the gallbladder and combined multiple hepatic anomalies, LSGB was highly suspected. During surgery after hilar dissection, we recognized that the tumor was located at the imaginary hilar bile duct bifurcation, but its actual location was corresponding to the biliary confluence of the left median and lateral sections. The extent of resection included extended left lateral sectionectomy, caudate lobe resection, and bile duct resection. Since some of the umbilical portion of the portal vein was invaded, it was resected and repaired with a portal vein branch patch. Due to anatomical variation of the biliary system, only one right-sided duct was reconstructed. The patient recovered uneventfully without any complication. LSGB should be recognized as a constellation of multiple hepatic anomalies, and therefore, thorough investigations are necessary to enable the performance of safe hepatic and biliary resections. PMID- 26155275 TI - Endovascular stenting of the inferior vena cava in a patient with Budd-Chiari syndrome and main hepatic vein thrombosis: a case report. AB - Endovascular stenting is accepted as an effective treatment for patients with Budd-Chiari syndrome (BCS). We herein present a case of successful endovascular treatment. A 46-year-old woman, who was followed up for 10 years after a diagnosis of BCS, showed progression progressive of liver cirrhosis and deterioration deteriorated of liver function. Three main hepatic veins were thrombosed with complete occlusion of the suprahepatic of the inferior vena cava (IVC); thus, hepatic venous blood flow was draining into the inferior right hepatic veins through the intrahepatic collaterals and passed passing through the subcutaneous venous collaterals. She underwent endovascular stenting of the IVC for palliation. A septoplasty needle was passed through the occluded IVC through into the internal jugular vein access and then to access the femoral vein using a snare wire. Severe elastic recoiling was observed after balloon dilatation; thus, a 28*80 mm stenting was done inserted across the occlusion, and repeat double ballooning was performed. The final venogram shows showed restored IVC inflow. The patient began to lose body weight 1 day after stenting, and edema disappeared within 1 week. She is was doing well at the 6 month follow-up visit with nearly normal liver function and marked resolution of cutaneous venous engorgement. In conclusion, endovascular stenting appeared to be an effective treatment to alleviate portal pressure and to prevent BCS-associated complications; thus, endovascular stenting should be considered before marked hepatic vein stenosis or complete occlusion occurs in patients with BCS. PMID- 26155276 TI - Fenestration of liver cysts in polycystic liver disease to improve quality of life: a case report and literature review. AB - Polycystic liver disease (PCLD) is characterized by a large number of liver cysts scattered throughout the liver parenchyma. We herein intend to present the beneficial effect of palliative fenestration treatment on quality of life in a patient with symptomatic PCLD. A 48-year-old female patient had been followed up for 5 years for both polycystic liver and kidney diseases at another institution. During follow-up for last 1 year, we recognized that she had barely maintained her ability of function in daily activities due to progressive worsening of fatigue and dyspnea on exertion. The patient finally underwent surgical fenestration treatment. Multiple cysts in the enlarged liver were opened and the cyst walls were excised with electrocautery. No surgical complication occurred and the patient was discharged 10 days after the open fenestration surgery. The total liver volume was 3,870 ml before surgery and 3,125 ml at 1 week after surgery, showing a volume reduction of 19.3%. After surgery, her performance status improved significantly. In the present case, significant improvement in quality of life and daily activity performance was achieved after open fenestration treatment over 18 months of follow-up without disease recurrence. PMID- 26155277 TI - Toward angiogenesis of implanted bio-artificial liver using scaffolds with type I collagen and adipose tissue-derived stem cells. AB - BACKGROUNDS/AIMS: Stem cell therapies for liver disease are being studied by many researchers worldwide, but scientific evidence to demonstrate the endocrinologic effects of implanted cells is insufficient, and it is unknown whether implanted cells can function as liver cells. Achieving angiogenesis, arguably the most important characteristic of the liver, is known to be quite difficult, and no practical attempts have been made to achieve this outcome. We carried out this study to observe the possibility of angiogenesis of implanted bio-artificial liver using scaffolds. METHODS: This study used adipose tissue-derived stem cells that were collected from adult patients with liver diseases with conditions similar to the liver parenchyma. Specifically, microfilaments were used to create an artificial membrane and maintain the structure of an artificial organ. After scratching the stomach surface of severe combined immunocompromised (SCID) mice (n=4), artificial scaffolds with adipose tissue-derived stem cells and type I collagen were implanted. Expression levels of angiogenesis markers including vascular endothelial growth factor (VEGF), CD34, and CD105 were immunohistochemically assessed after 30 days. RESULTS: Grossly, the artificial scaffolds showed adhesion to the stomach and surrounding organs; however, there was no evidence of angiogenesis within the scaffolds; and VEGF, CD34, and CD105 expressions were not detected after 30 days. CONCLUSIONS: Although implantation of cells into artificial scaffolds did not facilitate angiogenesis, the artificial scaffolds made with type I collagen helped maintain implanted cells, and surrounding tissue reactions were rare. Our findings indicate that type I collagen artificial scaffolds can be considered as a possible implantable biomaterial. PMID- 26155278 TI - Prognostic effect of preoperative sequential transcatheter arterial chemoembolization and portal vein embolization for right hepatectomy in patients with solitary hepatocellular carcinoma. AB - BACKGROUNDS/AIMS: Both preoperative transcatheter arterial chemoembolization (TACE) alone and portal vein embolization (PVE) alone have a detrimental prognostic effect on the post-resection outcomes in patients with hepatocellular carcinoma (HCC). The main objective of this study was to assess the prognostic impact of preoperative TACE on the long-term survival outcomes in patients undergoing preoperative PVE and right liver resection for solitary HCC. METHODS: Patients who underwent macroscopic curative right liver resection of solitary HCC that lied between 3.0 and 7.0 cm (n=113) with or without preoperative TACE and PVE were selected for the study, making these subjects were divided into three groups; the TACE-PVE group (n=27), the PVE-alone group (n=13), and the control group (n=73). The subjects in the three groups were followed up for >=36 months or until death. RESULTS: The 1-, 3-, 5-, and 10-year overall patient survival rates of all 113 patients were 96.5%, 88.2%, 81.3% and 65.0%, respectively. The 1 , 3-, 5-, and 10-year overall patient survival rates were 96.3%, 83.4%, 83.4% and 47.6% respectively in the TACE-PVE group; 84.6%, 76.9%, 57.7% and 19.2% respectively in the PVE-alone group; and 98.6%, 91.7%, 85.1% and 81.7% respectively in the control group (p=0.047). Patients were also sub-grouped according to tumor size, and those with a tumor of up to cutoff at 5 cm showed no prognostic difference (p=0.774), but tumor size >5 cm was associated with inferior patient survival only in the TACE-PVE group (p=0.018). CONCLUSIONS: Preoperative sequential TACE and PVE appear to be compliant to the conventional oncological concept in addition to induction of the future remnant liver regeneration. Therefore, we suggest that preoperative TACE should be come first whenever preoperative PVE for major hepatectomy is planned, especially in patients with hypervascular HCC tumors. PMID- 26155279 TI - Balloon dilation of jejunal afferent loop functional stenosis following left hepatectomy and hepaticojejunostomy long time after pylorus-preserving pancreaticoduodenectomy: a case report. AB - We present a rare case of functional stenosis of the jejunal loop following left hepatectomy and hepaticojejunostomy long after pylorus-preserving pancreaticoduodenectomy (PPPD), which was successfully managed by balloon dilation. A 70-year-old Korean man had undergone PPPD 6 years before due to 1.8 cm-sized distal bile duct cancer. Sudden onset of obstructive jaundice led to diagnosis of recurrent bile duct cancer mimicking perihilar cholangiocarcinoma of type IIIb. After left portal vein embolization, the patient underwent resection of the left liver and caudate lobe and remnant extrahepatic bile duct. The pre existing jejunal loop and choledochojejunostomy site were used again for new hepaticojejunostomy. The patient recovered uneventfully, but clamping of the percutaneous transhepatic biliary drainage (PTBD) tube resulted in cholangitis. Biliary imaging studies revealed that biliary passage into the afferent jejunal limb was significantly impaired. We performed balloon dilation of the afferent jejunal loop by using a 20 mm-wide balloon. Follow-up hepatobiliary scintigraphy showed gradual improvement in biliary excretion and the PTBD tube was removed at 1 month after balloon dilation. This very unusual condition was regarded as disuse atrophy of the jejunal loop, which was successfully managed by balloon dilation and intraluminal keeping of a large-bore PTBD tube for 1 month. PMID- 26155280 TI - Long-term outcome of ischemic type biliary stricture after interventional treatment in liver living donors: a report of two cases. AB - The wall of normal proximal bile duct is occasionally thin with close approximation to the right hepatic artery. Thus, isolation of this hepatic artery can result in excessive weakening of the remnant proximal bile duct wall during hemiliver graft harvest. This type of injury can induce ischemic stricture of the donor common bile duct. This study aimed to review the clinical sequences of such ischemic type donor bile duct injuries primarily managed with endoscopic and radiological interventional treatments. A retrospective review of medical records was performed for two living donors who suffered from ischemic type donor bile duct injury. They were followed up for more than 10 years. The right and left liver grafts were harvested from these two donors. Bile duct anatomy was normal bifurcation in one and anomalous branching in the other. Bile duct stenosis was detected in them at 2 weeks and 1 week after liver donation. They underwent endoscopic balloon dilatation and temporary stent (endoscopic retrograde biliary drainage tube) insertion. After keeping the tube for 2 months, the tube was successfully removed in one donor. However, endoscopic treatment was not successful, thus additional radiological intervention was necessary in the other donor. On follow-up over 10 years, they are doing well so far with no recurrence of biliary stricture. Based on our limited experience, interventional treatment with subsequent long-term follow-up appears to be an essential and choice treatment for ischemic type biliary stricture occurring in liver living donors. PMID- 26155281 TI - Bilateral ovarian metastasis from distal common bile duct carcinoma developing after choledochal cyst excision. AB - Ovarian metastases represent about 3-5% of all ovarian malignancies. Most of these tumors originate in the digestive tract and cholangiocarcinoma rarely involves the ovary. A 60-year-old woman was admitted for the investigation of abdominal distension that had lasted 1 week. One and a half years prior, the patient had undergone choledochal cyst excision, Roux-en Y hepaticojejunostomy and cholecystectomy. Computed tomography scans of the abdomen revealed a papillary mass in the remnant distal common bile duct and enlargement of both ovaries with a huge amount of ascites. An explorative laparotomy disclosed no peritoneal seeding with resectable cholangiocarcinoma and bilateral ovarian mass. Pylorus-preserving pancreatoduodenectomy and bilateral salphingo-oophorectomy with hysterectomy were performed. Histologically, it was a well-differentiated adenocarcinoma and all surgical margins were free of tumor. Both ovarian masses were consistent with metastatic adenocarcinoma from the common bile duct. The patient received six cycles of postoperative adjuvant systemic chemotherapy, dying after 10 months due to pulmonary embolism. PMID- 26155282 TI - Gallstone ileus inducing obstructive jaundice at the afferent loop of Roux-en-Y hepaticojejunostomy after bile duct cancer surgery: a case report. AB - The diagnosis of gallstone ileus is occasionally challenging due to the variability of its presentation. We herein present a very rare case of gallstone ileus inducing obstructive jaundice at the afferent loop of Roux-en-Y hepaticojejunostomy after 10 years of bile duct cancer surgery. We describe the case of a 74-year-old Korean woman with obstructive jaundice, treated conservatively. She showed severely impaired liver function test and obstructive jaundice. The computed tomography (CT) scan led to a diagnosis of very rare type of gallstones ileus at the afferent jejunal loop. Since the clinical manifestation was improved, we decided to observe her closely. On the next follow up CT scan, the gallstone disappeared with mild distension of the afferent bowel loop, implicating spontaneous passage of the gallstone. She recovered and returned to normal life after 10 days of initiation of clinical manifestations. We presume that the gallstone may enter the afferent jejunal loop through the hepaticojejunostomy and later increase in size. The presence of narrow tract of intestine may facilitate the incidence of gallstone ileus. It appears to be the first report on this rare type of gallstone ileus inducing obstructive jaundice. PMID- 26155283 TI - A rare case of gallbladder torsion along the axis of body: a case report. AB - Abnormal attachment of the gallbladder to the liver is the main cause for gallbladder torsion. However, the present study reports a rare case of gallbladder torsion in which a portion of fundus is rotated along the axis of body. So far, very few similar cases have been reported. An 87-year-old woman complaining right upper quadrant abdominal pain for 4 days was admitted. Her body temperature was 38.5C with moderate dehydration. A large tender mass was palpated on the right abdomen extending to the right iliac fossa. Computed tomography of abdomen showed a large cavity with a diameter of 15 cm containing a big stone and a small normal looking gallbladder. Ultrasonographic scan showed a twisted portion of the gallbladder torsion. During emergency laparotomy, the middle portion of the gallbladder was found to be twisted counterclockwise with huge gangrenous gallbladder distal. The proximal body of the gallbladder was spared and attached firmly to the liver. Cholecystectomy was performed and the patient was discharged 2 weeks later without postoperative complications. Histological findings of specimen were consistent with operative findings. The current study reports on a rare case of gallbladder torsion by reviewing previous studies. PMID- 26155284 TI - Gallbladder neck cancer and perihilar cholangiocarcinoma - siblings, cousins or look alikes? AB - The gallbladder neck cancer and perihilar cholangiocarcinoma present as painless progressive surgical obstructive jaundice. Sometimes it becomes difficult to differentiate between them even on cross-sectional imaging studies including computed tomography and magnetic resonance imaging. Staging laparoscopy and positron emission tomography may be useful in detecting metastases in gallbladder neck cancer, but are not recommended in perihilar cholangiocarcinoma. Most patients with gallbladder neck cancer and perihilar cholangiocarcinoma require preoperative biliary drainage. The differentiation is, however, important because their behavior and prognosis are totally different. Gallbladder neck cancer is biologically aggressive, thus long-term surviver are rare even after major resection. On the other hand, perihilar cholangiocarcinoma is often less aggressive and major proceduresresections are justified. Gallbladder neck cancer and perihilar cholangiocarcinoma, though not siblings, they tend to look alike sometimes. PMID- 26155285 TI - The Basic Facts of Korean Breast Cancer in 2012: Results from a Nationwide Survey and Breast Cancer Registry Database. AB - The Korean Breast Cancer Society has constructed a nationwide breast cancer database through utilization of an online registration program. We have reported the basic facts about breast cancer in Korea in 2012, and analyzed the changing patterns in the clinical characteristics and management of breast cancer in Korea over the last 10 years. Data on patients newly diagnosed with breast cancer were collected for the year 2012 from 97 hospitals and clinics nationwide using a questionnaire survey, and from the online registry database. A total of 17,792 patients were newly diagnosed with breast cancer in 2012. The crude incidence rate of female breast cancer, including invasive cancer and in situ cancer, was 70.7 cases per 100,000 women. The median age at diagnosis was 51 years, and the proportion of postmenopausal women was higher than that of premenopausal women among those diagnosed with breast cancer. The proportion of cases of early breast cancer increased continuously, and breast-conserving surgery was performed in more cases than total mastectomy in that same year. The total number of breast reconstruction surgeries increased approximately 3-fold over last 10 years. The 5 year overall survival rate for all stages of breast cancer patients was extremely high. The clinical characteristics of breast cancer have changed in ways that resulted in high overall survival over the past 10 years in Korea, and the surgical management of the disease has changed accordingly. Analysis of nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea. PMID- 26155286 TI - Isocryptotanshinone Induced Apoptosis and Activated MAPK Signaling in Human Breast Cancer MCF-7 Cells. AB - PURPOSE: Isocryptotanshinone (ICTS) is a natural bioactive product that is isolated from the roots of the widely used medical herb Salvia miltiorrhiza. However, few reports exist on the mechanisms underlying the therapeutic effects of ICTS. Here, we report that ICTS has anticancer activity and describe the mechanism underlying this effect. METHODS: The antiproliferative effect of ICTS was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and clonogenic assays. The effect of ICTS on the cell cycle was measured using flow cytometry. Apoptosis was determined by Hoechst 33342 staining, DNA fragmentation assays, and Western blotting for apoptotic proteins. Finally, the effect of ICTS on mitogen-activated protein kinases (MAPKs) was determined by Western blotting. RESULTS: ICTS significantly inhibited proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 human liver cancer cells, and A549 human lung cancer cells in vitro. Among the tested cell lines, MCF-7 cells showed the highest sensitivity to ICTS. ICTS significantly inhibited colony formation by MCF-7 cells. Furthermore, exposure of MCF-7 cells to ICTS induced cell cycle arrest at the G1 phase and decreased mitochondrial membrane potential. Hoechst 33342 staining and Western blot analysis for apoptotic proteins suggested that ICTS induced apoptosis in MCF-7 cells. In addition, ICTS activated MAPK signaling in MCF-7 cells by inducing time and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK. CONCLUSION: Our results suggest that ICTS inhibited MCF-7 cell proliferation by inducing apoptosis and activating MAPK signaling pathways. PMID- 26155287 TI - Vitamin D Receptor Poly(A) Microsatellite Polymorphism and 25-Hydroxyvitamin D Serum Levels: Association with Susceptibility to Breast Cancer. AB - PURPOSE: According to previous studies, vitamin D exhibits protective effects against breast cancer via the vitamin D receptor (VDR). There is growing evidence that breast cancer incidence is associated with various polymorphisms of the VDR gene. This study investigates the association of VDR poly(A) microsatellite variants with 25-hydroxyvitamin D (25(OH)D) serum levels and breast cancer risk. METHODS: Polymorphism analysis was performed on a total of 261 blood samples, which were collected from 134 women with breast cancer and 127 controls. Single strand conformation polymorphism was assessed by polymerase chain reaction in combination with sequencing to detect poly(A) lengths for each sample. The vitamin D levels of samples were determined by electrochemiluminescence. RESULTS: The poly(A) variant L allele frequency was significantly higher in cancer patients than in controls (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.16-2.57; p=0.006). Thus, carriers of the L allele (LS and LL genotypes) have a higher risk for breast cancer (OR, 1.86; 95% CI, 1.13-3.05; p=0.013). A larger increase in the risk for breast cancer was found in individuals with the L carrier genotype and lowered 25(OH)D levels. CONCLUSION: The results primarily suggest that VDR gene polymorphism in the poly(A) microsatellite is associated with 25(OH)D levels and that it can affect the breast cancer risk in the female population from northern Iran. PMID- 26155288 TI - Recombinant Human Granulocyte Colony-Stimulating Factor Promotes Preinvasive and Invasive Estrogen Receptor-Positive Tumor Development in MMTV-erbB2 Mice. AB - PURPOSE: We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could promote the development of preinvasive and invasive breast cancer in mouse mammary tumor virus (MMTV-erbB2) mice with estrogen receptor positive tumors. METHODS: MMTV-erbB2 mice were randomly divided into three experimental groups with 20 mice in each group. MMTV-erbB2 mice were treated with daily subcutaneous injections of vehicle or rhG-CSF (low-rhG-CSF group, rhG-CSF 0.125 ug; vehicle-rhG-CSF group, normal saline 0.25 ug; and high-rhG-CSF group, rhG-CSF 0.25 ug) at 3 months of age. Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction. RESULTS: Low, but not high, rhG-CSF doses significantly accelerated mammary tumorigenesis in MMTV-erbB2 mice. Short term treatment with rhG-CSF could significantly promote the development of preinvasive mammary lesions. The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%. CONCLUSION: We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo. Identification of G-CSF genes helped us further understand the mechanism by which G-CSF promotes cancer. Low doses of rhG-CSF could significantly increase tumor latency and increase tumor multiplicity and burden. Moreover, rhG-CSF effectively promotes development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice. PMID- 26155289 TI - Influence of Androgen Receptor Expression on the Survival Outcomes in Breast Cancer: A Meta-Analysis. AB - PURPOSE: Despite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer. METHODS: We searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression. RESULTS: There were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26 0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73). CONCLUSION: Expression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes. PMID- 26155290 TI - Breast Cancer Subtype as a Predictor of Lymph Node Metastasis according to the SEER Registry. AB - PURPOSE: Breast cancer subtype correlates with response to systemic therapy and overall survival (OS), but its impact on lymphatic spread is incompletely understood. In this study, we used the Surveillance, Epidemiology, and End Results registry to assess whether the subtype can predict the presence of nodal metastasis or advanced nodal stage in breast cancer. METHODS: A total of 7,274 eligible patients diagnosed with T1-3 infiltrating ductal carcinoma with known estrogen or progesterone hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, who underwent surgical excision of the primary tumor and pathologic lymph node evaluation, were included in this analysis. Patients were categorized into four breast cancer subtypes: HR+/HER2-; HR+/HER2+; HR /HER2+; and HR-/HER2-. Binary logistic regression analysis was used to determine whether breast cancer subtype, tumor size, tumor grade, patient race, and patient age at diagnosis are independently predictive of lymph node positivity or advanced nodal stage. The Pearson chi-square test was used to determine whether progesterone receptor (PR) status had an impact on the incidence of lymph node positivity in estrogen receptor (ER) positive patients. RESULTS: Independent predictors of nodal positivity included breast cancer subtype (p=0.040), tumor size (p<0.001), tumor grade (p<0.001), and patient age (p<0.001), whereas only tumor size (p<0.001), grade (p=0.001), and patient age (p=0.005) predicted advanced nodal stage. Triple-negative cancers had a significantly lower risk of nodal positivity than the HR+/HER2- subtype (odds ratio, 0.686; p=0.004), but no other significant differences between subtypes were observed. There was also no difference in lymph node positivity between PR+ and PR- tumors amongst ER+/HER2- (p=0.228) or ER+/HER2+ tumors (p=0.713). CONCLUSION: The HR+/HER2-breast cancer subtype has a higher rate of lymph node involvement at diagnosis than the triple negative subtype. These findings may play a role in guiding regional management considerations if confirmed in further studies. PMID- 26155291 TI - Differences in Clinical Outcomes between Luminal A and B Type Breast Cancers according to the St. Gallen Consensus 2013. AB - PURPOSE: Human epidermal growth factor receptor 2 (HER2)-positive luminal B type comprises estrogen receptor (ER)-positive and HER2-positive cancers, and HER2 negative luminal B type comprises ER-positive cancers showing a Ki-67 labeling index >=14% or progesterone receptor (PR) expression of <20% according to the St. Gallen consensus 2013. The current study aimed to classify intrinsic subtypes according to the St. Gallen consensus 2013 and determine the differences in clinicopathological parameters and survival outcomes among the molecular types, especially among the luminal types. METHODS: Assessment of molecular types was performed for 267 invasive ductal carcinomas. The differences in clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) among the molecular types were analyzed. RESULTS: The luminal B type was the most prevalent, at 44.9%, followed by the luminal A, triple-negative (including basal-like type), and HER2 type, at 21.7%, 18.7%, and 14.6%, respectively. There were statistically significant differences in size (p=0.003), nodal status (p=0.046), histologic grade (p<0.001), p53 (p<0.001) and cyclooxygenase 2 (COX-2) positivity (p=0.002), recurrence (p=0.001) and death rates (p=0.036), DFS (p=0.002), and OS (p=0.039) among the molecular types. Significant differences in size (p=0.009), nodal metastasis (p=0.019), histologic grade (p<0.001), p53 positivity (p=0.001), and PR expression (p<0.001) were noted between the luminal A and B types. Among the luminal B type cancers, the distributions of ER and PR scores showed significant differences (p=0.003, p=0.003). p53 positivity in the luminal B type cancers was related to shortened DFS (p=0.034). In luminal type cancers, COX-2 positivity was related to longer DFS (p=0.026). CONCLUSION: Different management guidelines should be considered for the luminal A and luminal B breast cancer types. Positive p53 expression in luminal B type cancers and negative COX-2 expression in luminal type cancers seem to be related to poor clinical outcome. PMID- 26155292 TI - Risk Factors Associated with Distant Metastasis and Survival Outcomes in Breast Cancer Patients with Locoregional Recurrence. AB - PURPOSE: To decide the optimal treatment for breast cancer patients with locoregional recurrence (LRR), it is important to determine which group has the highest risk of subsequent distant metastasis (DM). We aimed to investigate the factors associated with DM in patients with LRR. METHODS: We reviewed the data of 208 patients with LRR as the first event after primary surgery for breast cancer at our institution between 1997 and 2010, to identify significant factors associated with DM. Subsequently, Kaplan-Meier curves and the Cox regression method were used to analyze the correlation between clinical factors and survival. RESULTS: DM occurred in 33.2% (68/208) of LRR patients. The median DM free interval was 23 months. Some clinical factors were associated with DM in univariate analysis, including the type of primary surgery (p=0.026), tumor size (p=0.005), nodal status (p=0.011), and administration of initial adjuvant chemotherapy (p=0.001). In addition, regional rather than local recurrence and a disease-free interval (DFI; duration between primary surgery and LRR) <=30 months were also significant (p<0.001 for both). However, only a shorter DFI reached significance in multiple logistic regression analysis. Cox regression analysis of DM-free survival showed that both a shorter DFI and regional recurrence were significant factors with hazard ratios of 2.1 (95% confidence interval [CI], 1.21 3.65) and 1.85 (95% CI, 1.04-3.28), respectively. CONCLUSION: DFI was the most important factor associated with subsequent DM in patients with LRR as a first event of failure. PMID- 26155293 TI - Treatment Outcome of Breast Cancer with Pathologically Proven Synchronous Ipsilateral Supraclavicular Lymph Node Metastases. AB - PURPOSE: The aim of this study was to investigate the prognosis, patterns of failure, and prognostic factors for breast cancer patients with pathologically proven synchronous ipsilateral supraclavicular lymph node (ISCLN) metastases. METHODS: We reviewed the records of breast cancer patients with pathologically proven ISCLN metastases. Local aggressive treatment was defined as treatment including surgery, axillary lymph node dissection (ALND), ISCLN excision, radiotherapy (RT), and chemotherapy. RESULTS: A total of 111 patients were included. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 64.2% and 56.2%, respectively. On univariate analysis, RT, ALND, trastuzumab treatment, hormone receptor (HR) status, and local aggressive treatment were identified as significant factors for OS. The 5-year OS for 73 patients who received local aggressive treatment was superior to that of 38 patients who received nonaggressive treatment (70.9% vs. 49.3%, p=0.036). Multivariate analysis showed that RT, HR status, and trastuzumab were significant variables for the 5-year OS and DFS. CONCLUSION: Multimodality treatment with surgery, taxane-based chemotherapy, hormone therapy, and RT is strongly recommended for breast cancer patients with synchronous ISCLN metastases. PMID- 26155294 TI - Axillary Lymph Node-to-Primary Tumor Standard Uptake Value Ratio on Preoperative (18)F-FDG PET/CT: A Prognostic Factor for Invasive Ductal Breast Cancer. AB - PURPOSE: This study assessed the axillary lymph node (ALN)-to-primary tumor maximum standard uptake value (SUVmax) ratio (ALN/T SUV ratio) in invasive ductal breast cancer (IDC) on preoperative (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to determine the effectiveness in predicting recurrence-free survival (RFS). METHODS: One hundred nineteen IDC patients (mean age, 50.5+/-10.5 years) with pathologically proven ALN involvement without distant metastasis and preoperative FDG PET/CT were enrolled in the study. SUVmax values of the ALN and primary tumor were obtained on FDG PET/CT, and ALN/T SUV ratio was calculated. Several factors were evaluated for their effectiveness in predicting RFS. These included several parameters on FDG PET/CT as well as several clinicopathological parameters: pathologic tumor/node stage; nuclear and histological grade; hormonal state; status with respect to human epidermal growth factor receptor 2, mindbomb E3 ubiquitin protein ligase 1 (MIB 1), and p53; primary tumor size; and ALN size. RESULTS: Among 119 patients with breast cancer, 17 patients (14.3%) experienced relapse during follow-up (mean follow-up, 28.4 months). The ALN/T SUV ratio of the group with disease recurrence was higher than that of the group without recurrence (0.97+/-1.60 and 0.45+/ 0.40, respectively, p=0.005). Univariate analysis showed that the primary tumor SUVmax, ALN SUVmax, ALN/T SUV ratio, ALN status, nuclear and histological grade, estrogen receptor (ER) status, and MIB-1 status were predictors for RFS. Among these variables, ALN/T SUV ratio with hazard ratio of 4.20 (95% confidence interval [CI], 1.74-10.13) and ER status with hazard ratio of 4.33 (95% CI, 1.06 17.71) were predictors for RFS according to multivariate analysis (p=0.002 and p=0.042, respectively). CONCLUSION: Our study demonstrated that ALN/T SUV ratio together with ER status was an independent factor for predicting relapse in IDC with metastatic ALN. ALN/T SUV ratio on preoperative FDG PET/CT may be a useful marker for selecting IDC patients that need adjunct treatment to prevent recurrence. PMID- 26155295 TI - Synchronous BI-RADS Category 3 Lesions on Preoperative Ultrasonography in Patients with Breast Cancer: Is Short-Term Follow-Up Appropriate? AB - PURPOSE: Breast ultrasonography (US) has been widely used in the preoperative examination of patients with breast cancer. Breast Imaging Reporting and Data System (BI-RADS) category 3 (C3) lesions (probably benign) are regarded as having a low probability of malignancy (<=2%). The purposes of this study were to verify the malignancy rates for synchronous BI-RADS C3 lesions in patients with breast cancer and consider appropriate management strategies for these lesions. METHODS: Between January 2010 and January 2013, a total of 161 patients underwent surgery in our institute for breast cancer and synchronous BI-RADS C3 lesions. In the US reports, we found records of 219 synchronous BI-RADS C3 nodules in 161 patients. They were excised during surgery for breast cancer management. Stepwise logistic regression analysis was used to identify predictors of malignancy for synchronous BI-RADS C3 lesions. RESULTS: The rate of malignancy among the 219 BI-RADS C3 lesions was 9.6%. In simple logistic regression analysis, the size of the primary tumor (p<0.001), pathologic T (pT) stage (p=0.002), and progesterone receptor (PR) status of the primary tumor (p=0.029) were significant predictive factors. In multiple logistic regression analysis, the pT stage and PR status of the primary tumor remained significant predictors (p=0.004 and p=0.003, respectively), and human epidermal growth factor receptor 2 (HER2) was identified as another significant factor (p=0.006). CONCLUSION: In patients with breast cancer who are scheduled for surgery, needle biopsy or excision should be considered for synchronous BI-RADS C3 lesions identified on preoperative US when the primary tumor has the following risk factors: large size, high PR expression, and HER2 positivity. PMID- 26155296 TI - Magnetic Resonance Imaging Features of Adenosis in the Breast. AB - PURPOSE: Adenosis lesions of the breast, including sclerosing adenosis and adenosis tumors, are a group of benign proliferative disorders that may mimic the features of malignancy on imaging. In this study, we aim to describe the features of breast adenosis lesions with suspicious or borderline findings on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: In our database, we identified 49 pathologically proven breast adenosis lesions for which the final assessment of the breast MRI report was classified as either category 4 (n=45) or category 5 (n=4), according to the Breast Imaging Reporting and Data System (BI-RADS) published by the American College of Radiology (ACR). The lesions had a final diagnosis of either pure adenosis (n=33, 67.3%) or mixed adenosis associated with other benign pathologies (n=16, 32.7%). RESULTS: Of the 49 adenosis lesions detected on DCE-MRI, 32 (65.3%) appeared as enhancing masses, 16 (32.7%) as nonmass enhancements, and one (2.1%) as a tiny enhancing focus. Analysis of the enhancing masses based on the ACR BI-RADS lexicon revealed that among the mass descriptors, the most common features were irregular shape in 12 (37.5%), noncircumscribed margin in 20 (62.5%), heterogeneous internal pattern in 16 (50.0%), rapid initial enhancement in 32 (100.0%), and wash-out delayed en hancement pattern in 21 (65.6%). Of the 16 nonmass enhancing lesions, the most common descriptors included focal distribution in seven (43.8%), segmental distribution in six (37.5%), clumped internal pattern in nine (56.3%), rapid initial enhancement in 16 (100.0%), and wash-out delayed enhancement pattern in eight (50.0%). CONCLUSION: Adenosis lesions of the breast may appear suspicious on breast MRI. Awareness of these suspi-cious-appearing features would be helpful in obviating unnecessary breast biopsies. PMID- 26155297 TI - Dermatomyositis and Paclitaxel-Induced Cutaneous Drug Eruption Associated with Metastatic Breast Cancer. AB - Dermatomyositis (DM) is an idiopathic autoimmune connective disease characterized by muscles and skin inflammation of and a well-recognized association with several human malignancies, especially breast cancer. Paclitaxel is a taxane antineoplastic agent with therapeutic effects against a wide range of cancers including breast cancer. This drug is well known for neurotoxicity and hypersensitivity reactions. However, cutaneous drug eruptions, especially those of grade III or higher, are not frequent. Here, we describe the case of a 55-year old woman with metastatic breast cancer who developed paraneoplastic DM and a paclitaxel-induced exanthematous drug eruption. This case report emphasizes the importance of evaluating internal malignancies, such as advanced breast cancer, in newly developed DM patients. In addition, it presents a rare case of paclitaxel-induced exanthematous drug eruption. The purpose of this case report highlights the immunological pathogenic mechanism of DM and drug eruption in underlying advanced breast cancer. PMID- 26155298 TI - Primary Inflammatory Myofibroblastic Tumors of the Breast with Metastasis: Radiographic and Histopathologic Predictive Factors. AB - Primary inflammatory myofibroblastic tumors (IMTs) of the breast are uncommon and metastasis of IMTs is extremely rare. To date, the natural course of this disease is not fully understood. Although patients with IMTs should undergo regular follow-up after complete surgical resection of the tumor, the appropriate interval and method of follow-up are unclear. We report the case of a patient with an IMT of the breast that metastasized 2 years after complete surgical resection. This unusual case emphasizes the importance of preoperative examinations to determine whether the IMT has atypical features that should guide the interval and method of follow-up. PMID- 26155300 TI - Health status and health-related quality of life of municipal waste collection workers - a cross-sectional survey. AB - BACKGROUND: Waste collection workers are exposed to several occupational stressors which may affect their quality of life. Our aim was to assess the health status and health-related quality of life (HRQoL) of municipal waste collection workers of a big German city. METHODS: Cross-sectional study with a non-random sample of 65 (62 male, 3 female) workers of the Hamburg sanitation department, volunteering to participate in the study. We assessed the prevalence of reported health complaints and health problems. HRQoL was assessed with the self-administered EQ-5D-5L questionnaire and its visual analogue scale (VAS). RESULTS: The most common health problems were musculoskeletal complaints (back pain reported by 67.2 %, other musculoskeletal complaints 15.4 %). Asthma or chronic obstructive pulmonary disease (COPD) was reported by 15.4 % of the workers. All participants reporting having a diagnosis of asthma or COPD had been or were active smokers. Our findings indicate an impaired HRQoL among the investigated occupational group. Regarding EQ-5D 68.3 % reported at least "slight" problems in one or more dimensions, and almost one third (31.7 %) reported "no problems" in any dimension. Problems were most frequently reported in the dimension "pain/discomfort" (64.1 % of the workers). The mean VAS value was 80.9 (13.2). The presence of back pain was associated with limitations in HRQoL (RR 3.1; 95 %-CI 1.5-6.1). The EQ5D VAS score was statistically significantly lower among waste collectors with back pain (77.9 SD 14.1) compared to those with no back complaints (88.0 SD 7.6, p < 0.01). CONCLUSIONS: Back complaints are common among municipal waste collectors and are associated with considerable impairments in their HRQoL. Interventions to enhance ergonomic work are needed in order to reduce back complaints and enhance HRQoL in this occupational group. PMID- 26155299 TI - Psychosocial treatment and interventions for bipolar disorder: a systematic review. AB - BACKGROUND: Bipolar disorder (BD) is a chronic disorder with a high relapse rate, significant general disability and burden and with a psychosocial impairment that often persists despite pharmacotherapy. This indicates the need for effective and affordable adjunctive psychosocial interventions, tailored to the individual patient. Several psychotherapeutic techniques have tried to fill this gap, but which intervention is suitable for each patient remains unknown and it depends on the phase of the illness. METHODS: The papers were located with searches in PubMed/MEDLINE through May 1st 2015 with a combination of key words. The review followed the recommendations of the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses statement. RESULTS: The search returned 7,332 papers; after the deletion of duplicates, 6,124 remained and eventually 78 were included for the analysis. The literature supports the usefulness only of psychoeducation for the relapse prevention of mood episodes and only in a selected subgroup of patients at an early stage of the disease who have very good, if not complete remission, of the acute episode. Cognitive-behavioural therapy and interpersonal and social rhythms therapy could have some beneficial effect during the acute phase, but more data are needed. Mindfulness interventions could only decrease anxiety, while interventions to improve neurocognition seem to be rather ineffective. Family intervention seems to have benefits mainly for caregivers, but it is uncertain whether they have an effect on patient outcomes. CONCLUSION: The current review suggests that the literature supports the usefulness only of specific psychosocial interventions targeting specific aspects of BD in selected subgroups of patients. PMID- 26155301 TI - Factors associated exclusive breastfeeding practices of urban women in Addis Ababa public health centers, Ethiopia: a cross sectional study. AB - BACKGROUND: Exclusive breastfeeding (EBF) is the best nutrition for the children during the first 6 months of life, yet despite knowing the clear benefits, the practice of EBF is low. The aim of the study is to determine prevalence of exclusive breastfeeding practice and associated factors in Addis Ababa. METHODS: A facility based cross-sectional study with internal comparison was conducted among 648 mothers attending immunization sessions in all public health centers in Addis Ababa, Ethiopia, in February 2011. Prevalence of EBF was determined using 'recall since birth' method. Multiple logistic regression was used to adjust for confounding effects while determining the association between exclusive breastfeeding practice and selected factors. RESULTS: The prevalence of EBF under six months was 29.3 % (95 % CI 25.9, 32.9). Mothers whose monthly income 500 - 1000birr (US$56 - 113) were more likely to exclusively breastfeed than those who earn more than 1000birr (US$113) (Adjusted Odds Ratio [AOR] = 2.49; 95 % Confidence Interval [CI] 1.06, 5.88). Mothers who reported having antenatal counseling (AOR = 1.99; 95 % CI 1.16, 3.43) and postnatal counseling were more likely to exclusively breastfeed than those who did not have counseling (AOR = 2.12; 95 % CI 1.28, 3.54). Mothers who gave birth vaginally were more likely to exclusively breastfeed than those who had a Caesarean section (AOR = 2.40; 95 % CI 1.25, 4.61). CONCLUSIONS: The prevalence of exclusive breastfeeding was low in Addis Ababa. Mothers' income, antenatal and postnatal counseling and mode of delivery were found to be associated with EBF practices. Recommendations include strengthening nutrition counseling during antenatal and postnatal sessions, further exploring the barriers to EBF for higher income mothers and offering continuous assistance and safe pain relief medication for mothers who gave birth by caesarean section. PMID- 26155302 TI - Focused abdominal sonography for trauma in the clinical evaluation of children with blunt abdominal trauma. AB - INTRODUCTION: In pediatric care, the role of focused abdominal sonography in trauma (FAST) remains ill defined. The objective of this study was to assess the sensitivity and specificity of FAST for detecting free peritoneal fluid in children. METHODS: The trauma registry of a single level I pediatric trauma center was queried for the results of FAST examination of consecutive pediatric (<18 years) blunt trauma patients over a period of 36 months, from January 2010 to December 2012. Demographics, type of injuries, FAST results, computerized tomography (CT) results, and operative findings were reviewed. RESULTS: During the study period, 543 injured pediatric patients (mean age 8.2 +/- 5 years) underwent FAST examinations. In 95 (17.5 %) FAST was positive for free peritoneal fluid. CT examination was performed in 219 (40.3 %) children. Positive FAST examination was confirmed by CT scan in 61/73 (83.6 %). CT detected intra peritoneal fluid in 62/448 (13.8 %) of the patients with negative FAST results. These findings correspond to a sensitivity of 50 %, specificity of 88 %, positive predictive value (PPV) of 84 %, and a negative predictive value (NPV) of 58 %. In patients who had negative FAST results and no CT examination (302), no missed abdominal injury was detected on clinical ground. FAST examination in the young age group (<2 years) yielded lower sensitivity and specificity (36 and 78 % respectively) with a PPV of only 50 %. CONCLUSIONS: This study shows that although a positive FAST evaluation does not necessarily correlate with an IAI, a negative one strongly suggests the absence of an IAI, with a high NPV. These findings are emphasized in the analysis of the subgroup of children less than 2 years of age. FAST examination tempered with sound clinical judgment seems to be an effective tool to discriminate injured children in need of further imaging evaluation. PMID- 26155303 TI - Inferior vena cava enteric fistula due to unresected colorectal metastasis. AB - A 57 year old male presented to our department with recurrent attacks of sepsis and upper gastrointestinal bleeding due to colorectal cancer metastasis that resulted in a fistula involving the inferior vena cava and the third part of the duodenum. Four and a half years ago he underwent laparoscopic right hemicolectomy due to colonic adenocarcinoma. A year prior to his recent hospitalization he underwent cytoreductive surgery followed by HIPEC due to peritoneal metastases in another hospital. During the operation a metastasis adherent to the inferior vena cava and the III part of the duodenum was revealed. The surgeon decided to mark the area with hemo- clips and after the patient recovered from surgery he was sent for radiotherapy aimed at controlling the left over metastases. In his current hospitalization he underwent an en bloc resection of the III part of the duodenum, the adherent vena cava and the right kidney. Gross pathology revealed a fistula between the vena cava and the duodenum with bile stained clot within the resected part of the vena cava. The patient recovered well with resolutions of his presenting symptoms. PMID- 26155304 TI - Panax Notoginseng flower saponins (PNFS) inhibit LPS-stimulated NO overproduction and iNOS gene overexpression via the suppression of TLR4-mediated MAPK/NF-kappa B signaling pathways in RAW264.7 macrophages. AB - BACKGROUND: Panax Notoginseng flower saponins (PNFS) are the main active component of Panax notoginseng (Burk) F. H. Chen flower bud (PNF) and possess significant anti-inflammatory efficacy. This study aims to explore the mechanisms underlying PNFS' antiflammatory action in RAW264.7 macrophages. METHODS: A cell counting kit-8 assay was used to determine the viability of RAW264.7 macrophages. Anti-inflammation effects of PNFS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were measured based on the detection of nitric oxide (NO) overproduction (Griess method, DAF-FM DA fluorescence assay and NO2 (-) scavenging assay), and interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha gene overexpression (real-time PCR and ELISA). Inducible nitric oxide synthase (iNOS) gene overexpression was determined by real-time PCR and western blotting. iNOS enzyme activity was also assayed. The mechanisms underlying the suppression of iNOS gene overexpression by PNFS were explored using real-time PCR and western blotting to assess mRNA and protein levels of components of the Toll-like receptor 4 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor-kappa B (NF-kappa B) signaling pathways. RESULTS: PNFS (50, 100, 200 MUg/mL) significantly reduced LPS-induced overproduction of NO (P < 0.001, P < 0.001, P < 0.001) and IL-6 (P = 0.103, P < 0.001, P < 0.001), but did not affect TNF-alpha overproduction. PNFS (50, 100, 200 MUg/mL) also markedly decreased LPS-activated iNOS (P < 0.001, P < 0.001, P < 0.001) and TLR4 gene overexpression (P = 0.858, P = 0.046, P = 0.005). Furthermore, treatment with PNFS (200 MUg/mL) suppressed the phosphorylation of MAPKs including P38 (P = 0.001), c-Jun N-terminal kinase (JNK) (P = 0.036) and extracellular-signal regulated kinase (ERK) 1/2 (P = 0.021). PNFS (200 MUg/mL) inhibited the activation of the NF-kappa B signaling pathway by preventing the phosphorylation of inhibitor of NF-kappa B alpha (I-kappa B alpha) (P = 0.004) and P65 (P = 0.023), but PNFS (200 MUg/mL) could not activate the LPS-induced PI3K-Akt signaling pathway. CONCLUSIONS: PNFS significantly down-regulated iNOS gene overexpression and thereby decreased NO overproduction via the inhibition of TLR4 mediated MAPK/NF-kappa B signaling pathways, but not the PI3K/Akt signaling pathway. PMID- 26155305 TI - Anti-leukemia activity of semi-synthetic phenolic derivatives from Polygonum limbatum Meisn. AB - BACKGROUND: The present report describes the semi-synthesis of a few O-prenylated phenolic derivatives and their in vitro antitumor activities. These compounds were prepared by modifying two naturally occurring antitumor phenols, 5,7 dihydroxy-3-(1'-hydroxy-1'-phenyl-methyl)-6-methoxy-chroman-4-one (A) and 2',4' dihydroxy-3',6'-dimethoxychalcone (B), previously isolated from Polygonum limbatum Meisn. (Polygonaceae). The structures were elucidated by spectroscopic means and comparison with published data. The cytotoxicity of compounds was determined by using the resazurin assay in the parental drug-sensitive CCRF-CEM cell line and its multidrug-resistant P-glycoprotein-over-expressing subline, CEM/ADR5000. RESULTS: We describe in the present paper four new semi-synthetic derivatives of A and B: 5-hydroxy-6-methoxy-7-O-(3'-methylbut-2'-enyl)chroman-4 one (1), trivially named metapchromone, 5-acetoxy-6-methoxy-7-O-[3'-methylbut 2'enyl]chroman-4-one (2), trivially named sargisin, 2'-hydroxy-3',6'-dimethoxy-4' O-(3"-methylbut-2"-enyl)chalcone (3) trivially named limbachalcone A, and 2' acetoxy-3',6'-dimethoxy-4'-O-(3"-methylbut-2"-enyl)chalcone (4) trivially named tsedengchalcone. Their preliminary cytotoxic activities have been determined. We also report herein the isolation of 1-methylhydantoin (C) and betulinic acid (D) from Polygonum limbatum for the first time. CONCLUSIONS: The study clearly suggests that semi-synthesis involving O-prenylation and acetylation of chalcones or other chromanones should be avoided in a search for anticancer drugs. This conclusion should be helpful when selecting substituents for the synthesis of potential anticancer drugs. PMID- 26155306 TI - Absorptive stripping voltammetry for cannabis detection. AB - BACKGROUND: Given that Delta(9)-tetrahydrocannabinol, the active constituent of cannabis, has been shown to greatly reduce driving ability, thus being linked to many drug driving accidents, its reliable detection is of great importance. RESULTS: An optimised carbon paste electrode, fabricated from graphite powder and mineral oil, is utilised for the sensitive detection of Delta(9) tetrahydrocannabinol (THC) in both aqueous solutions of pH 10.0 and in synthetic saliva solutions. "Absorptive Stripping Voltammetry" is exploited to that effect and the paste is used to pre-concentrate the carbon paste electrode with the target molecule. Practical limits of detection of 0.50 MUM and 0.10 MUM are determined for THC in stationary and stirred aqueous borate buffer solutions, respectively. Theoretical limits of detection are also calculated; values of 0.48 nM and 0.41 nM are determined for stationary and stirred THC aqueous borate buffer solutions, respectively. THC concentrations as low as 0.50 MUM are detected in synthetic saliva solutions. The sensitivity of the sensor was 0.12 MUA MUM(-1), 0.84 MUA MUM(-1) and 0.067 MUA MUM(-1) for the stationary buffer, the stirred buffer and the saliva matrix, respectively. CONCLUSIONS: "Absorptive Stripping Voltammetry" can be reliably applied to the detection of Delta(9) tetrahydrocannabinol, after suitable optimisation of the assay. Usefully low practical limits of detection can be achieved. PMID- 26155307 TI - Stakeholder analysis of the Programme for Improving Mental health carE (PRIME): baseline findings. AB - BACKGROUND: The knowledge generated from evidence-based interventions in mental health systems research is seldom translated into policy and practice in low and middle-income countries (LMIC). Stakeholder analysis is a potentially useful tool in health policy and systems research to improve understanding of policy stakeholders and increase the likelihood of knowledge translation into policy and practice. The aim of this study was to conduct stakeholder analyses in the five countries participating in the Programme for Improving Mental health carE (PRIME); evaluate a template used for cross-country comparison of stakeholder analyses; and assess the utility of stakeholder analysis for future use in mental health policy and systems research in LMIC. METHODS: Using an adapted stakeholder analysis instrument, PRIME country teams in Ethiopia, India, Nepal, South Africa and Uganda identified and characterised stakeholders in relation to the proposed action: scaling-up mental health services. Qualitative content analysis was conducted for stakeholder groups across countries, and a force field analysis was applied to the data. RESULTS: Stakeholder analysis of PRIME has identified policy makers (WHO, Ministries of Health, non-health sector Ministries and Parliament), donors (DFID UK, DFID country offices and other donor agencies), mental health specialists, the media (national and district) and universities as the most powerful, and most supportive actors for scaling up mental health care in the respective PRIME countries. Force field analysis provided a means of evaluating cross-country stakeholder power and positions, particularly for prioritising potential stakeholder engagement in the programme. CONCLUSION: Stakeholder analysis has been helpful as a research uptake management tool to identify targeted and acceptable strategies for stimulating the demand for research amongst knowledge users, including policymakers and practitioners. Implementing these strategies amongst stakeholders at a country level will hopefully reduce the knowledge gap between research and policy, and improve health system outcomes for the programme. PMID- 26155308 TI - The Chemical Validation and Standardization Platform (CVSP): large-scale automated validation of chemical structure datasets. AB - BACKGROUND: There are presently hundreds of online databases hosting millions of chemical compounds and associated data. As a result of the number of cheminformatics software tools that can be used to produce the data, subtle differences between the various cheminformatics platforms, as well as the naivety of the software users, there are a myriad of issues that can exist with chemical structure representations online. In order to help facilitate validation and standardization of chemical structure datasets from various sources we have delivered a freely available internet-based platform to the community for the processing of chemical compound datasets. RESULTS: The chemical validation and standardization platform (CVSP) both validates and standardizes chemical structure representations according to sets of systematic rules. The chemical validation algorithms detect issues with submitted molecular representations using pre-defined or user-defined dictionary-based molecular patterns that are chemically suspicious or potentially requiring manual review. Each identified issue is assigned one of three levels of severity - Information, Warning, and Error - in order to conveniently inform the user of the need to browse and review subsets of their data. The validation process includes validation of atoms and bonds (e.g., making aware of query atoms and bonds), valences, and stereo. The standard form of submission of collections of data, the SDF file, allows the user to map the data fields to predefined CVSP fields for the purpose of cross validating associated SMILES and InChIs with the connection tables contained within the SDF file. This platform has been applied to the analysis of a large number of data sets prepared for deposition to our ChemSpider database and in preparation of data for the Open PHACTS project. In this work we review the results of the automated validation of the DrugBank dataset, a popular drug and drug target database utilized by the community, and ChEMBL 17 data set. CVSP web site is located at http://cvsp.chemspider.com/. CONCLUSION: A platform for the validation and standardization of chemical structure representations of various formats has been developed and made available to the community to assist and encourage the processing of chemical structure files to produce more homogeneous compound representations for exchange and interchange between online databases. While the CVSP platform is designed with flexibility inherent to the rules that can be used for processing the data we have produced a recommended rule set based on our own experiences with the large data sets such as DrugBank, ChEMBL, and data sets from ChemSpider. PMID- 26155309 TI - Single Cell Assay for Molecular Diagnostics and Medicine: Monitoring Intracellular Concentrations of Macromolecules by Two-photon Fluorescence Lifetime Imaging. AB - Molecular organization of a cell is dynamically transformed along the course of cellular physiological processes, pathologic developments or derived from interactions with drugs. The capability to measure and monitor concentrations of macromolecules in a single cell would greatly enhance studies of cellular processes in heterogeneous populations. In this communication, we introduce and experimentally validate a bio-analytical single-cell assay, wherein the overall concentration of macromolecules is estimated in specific subcellular domains, such as structure-function compartments of the cell nucleus as well as in nucleoplasm. We describe quantitative mapping of local biomolecular concentrations, either intrinsic relating to the functional and physiological state of a cell, or altered by a therapeutic drug action, using two-photon excited fluorescence lifetime imaging (FLIM). The proposed assay utilizes a correlation between the fluorescence lifetime of fluorophore and the refractive index of its microenvironment varying due to changes in the concentrations of macromolecules, mainly proteins. Two-photon excitation in Near-Infra Red biological transparency window reduced the photo-toxicity in live cells, as compared with a conventional single-photon approach. Using this new assay, we estimated average concentrations of proteins in the compartments of nuclear speckles and in the nucleoplasm at ~150 mg/ml, and in the nucleolus at ~284 mg/ml. Furthermore, we show a profound influence of pharmaceutical inhibitors of RNA synthesis on intracellular protein density. The approach proposed here will significantly advance theranostics, and studies of drug-cell interactions at the single-cell level, aiding development of personal molecular medicine. PMID- 26155310 TI - Smart MoS2/Fe3O4 Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging. AB - The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during the cancer therapy. Here, magnetic targeted photothermal therapy was demonstrated by the integration of MoS2 (MS) flakes and Fe3O4 (IO) nanoparticles (NPs), where MoS2 converted near-infrared (NIR) light into heat and Fe3O4 NPs served as target moiety directed by external magnetic field to tumor site. The MoS2/Fe3O4 composite (MSIOs) functionalized by biocompatible polyethylene glycol (PEG) were prepared by a simple two-step hydrothermal method. And the as-obtained MSIOs exhibit high stability in bio-fluids and low toxicity in vitro and in vivo. Specifically, the MSIOs can be applied as a dual-modal probe for T2-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) imaging due to their superparamagnetic property and strong NIR absorption. Furthermore, we demonstrate an effective result for magnetically targeted photothermal ablation of cancer. All these results show a great potential for localized photothermal ablation of cancer spatially/timely guided by the magnetic field and indicated the promise of the multifunctional MSIOs for applications in cancer theranostics. PMID- 26155311 TI - A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy. AB - Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy. PMID- 26155312 TI - [18F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain. AB - We evaluated the efficacy of 2-[5-(4-[(18)F]fluoroethoxy-2-oxo-1,3-benzoxazol 3(2H)-yl)-N-methyl-N-phenylacetamide] ([(18)F]FEBMP) for positron emission tomography (PET) imaging of translocator protein (18 kDa, TSPO). Dissection was used to determine the distribution of [(18)F]FEBMP in mice, while small-animal PET and metabolite analysis were used for a rat model of focal cerebral ischemia. [(18)F]FEBMP showed high radioactivity uptake in mouse peripheral organs enriched with TSPO, and relatively high initial brain uptake (2.67 +/- 0.12% ID/g). PET imaging revealed an increased accumulation of radioactivity in the infarcted striatum, with a maximum ratio of 3.20 +/- 0.12, compared to non-injured striatum. Displacement with specific TSPO ligands lowered the accumulation levels in infarcts to those on the contralateral side. This suggests that the increased accumulation reflected TPSO-specific binding of [(18)F]FEBMP in vivo. Using a simplified reference tissue model, the binding potential on the infarcted area was 2.72 +/- 0.27. Metabolite analysis in brain tissues showed that 83.2 +/- 7.4% and 76.4 +/- 2.1% of radioactivity was from intact [(18)F]FEBMP at 30 and 60 min, respectively, and that this ratio was higher than in plasma (8.6 +/- 1.9% and 3.9 +/- 1.1%, respectively). In vitro autoradiography on postmortem human brains showed that TSPO rs6971 polymorphism did not affect binding sites for [(18)F]FEBMP. These findings suggest that [(18)F]FEBMP is a promising new tool for visualization of neuroinflammation. PMID- 26155313 TI - CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells. AB - Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6 GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future. PMID- 26155314 TI - DNA Aptamer Selected against Pancreatic Ductal Adenocarcinoma for in vivo Imaging and Clinical Tissue Recognition. AB - In this work, we have developed a truncated DNA aptamer, termed XQ-2d, with high affinity and specificity for pancreatic ductal adenocarcinoma (PDAC). Aptamer XQ 2d selectively binds to PL45 cells with a dissociation constant in the nanomolar range, as determined by its recognition of PL45 tumor cells in mice. Moreover, XQ 2d shows better recognition ratio for 40 tissue sections of clinical PDAC samples (82.5%) compared to the initial cell-SELEX selection library (5%). Therefore, XQ 2d can be considered a promising candidate as a tool for PDAC diagnosis and treatment. PMID- 26155315 TI - Concomitant Retrograde Coronary Venous Infusion of Basic Fibroblast Growth Factor Enhances Engraftment and Differentiation of Bone Marrow Mesenchymal Stem Cells for Cardiac Repair after Myocardial Infarction. AB - AIM: Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model. METHODS AND RESULTS: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1*10(8) cells) (n=5), MSCs (1*10(8) cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43+/-1.51% versus 10.07+/-2.94%; p<0.001). Morphologic analysis revealed an increased infarct wall thickness in the bFGF+MSCs group compared to all others (p<0.05), accompanied by increased vascular density and reduced apoptosis. Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05). CONCLUSIONS: Retrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury. PMID- 26155317 TI - An Innovative Strategy for the Fabrication of Functional Cell Sheets Using an Electroactive Conducting Polymer. AB - Here, we report the development of an electric field-assisted methodology for constructing 3D C2C12 cell sheets with the potential for cell surface modification. In this method, a conducting polymer, polypyrrole (Ppy), is electrodeposited via biotin doping, and then chemical conjugation of biotinylated bone morphogenetic protein 2 (BMP2) is achieved using a biotin-streptavidin cross linker. Subsequently, C2C12 cells are cultured on BMP2-immobilized Ppy surfaces to induce interactions between cell surface receptors and bound BMP2 ligands. Following these procedures, layers of BMP2-immobilized cells can be easily detached from the Ppy surface by applying an electrical potential. This novel method results in high affinity, ligand-bound cell sheets, which exhibit homogeneous coverage with membrane-bound proteins and signal activation that occurs via maximal receptor accessibility. Using this strategy to engineer the cell surface with desirable ligands results in structures that mimic in vivo tissues; thus, the method reported here has potential applications in regenerative medicine and tissue engineering. PMID- 26155316 TI - Current Approaches for Improving Intratumoral Accumulation and Distribution of Nanomedicines. AB - The ability of nanoparticles and macromolecules to passively accumulate in solid tumors and enhance therapeutic effects in comparison with conventional anticancer agents has resulted in the development of various multifunctional nanomedicines including liposomes, polymeric micelles, and magnetic nanoparticles. Further modifications of these nanoparticles have improved their characteristics in terms of tumor selectivity, circulation time in blood, enhanced uptake by cancer cells, and sensitivity to tumor microenvironment. These "smart" systems have enabled highly effective delivery of drugs, genes, shRNA, radioisotopes, and other therapeutic molecules. However, the resulting therapeutically relevant local concentrations of anticancer agents are often insufficient to cause tumor regression and complete elimination. Poor perfusion of inner regions of solid tumors as well as vascular barrier, high interstitial fluid pressure, and dense intercellular matrix are the main intratumoral barriers that impair drug delivery and impede uniform distribution of nanomedicines throughout a tumor. Here we review existing methods and approaches for improving tumoral uptake and distribution of nano-scaled therapeutic particles and macromolecules (i.e. nanomedicines). Briefly, these strategies include tuning physicochemical characteristics of nanomedicines, modulating physiological state of tumors with physical impacts or physiologically active agents, and active delivery of nanomedicines using cellular hitchhiking. PMID- 26155319 TI - Hypothesis on the Treatment of Gliomas with Acupuncture at the Primo Node Corresponding to Zusanli (ST 36). AB - Background: The primo vascular system (PVS) is an anatomical structure that is a network of ducts with fluid flowing in them, which are called primo vessels and correspond to acupuncture meridians, and primo nodes that correspond to acupoints. The PVS' main function is considered to be the maintenance of regenerative homeostasis in human and animal bodies. This system is distributed throughout the bodies of normal animals and develops around and in cancer tissues. This cancer-associated PVS may be a critical metastatic path besides the blood and the lymph vessels. The author of this article proposes a hypothesis on cancer treatment: Injecting anticancer drugs into acupoints according to the pharmacopuncture method can be effective as a result of the flow channels of the PVS. The author considers the acupoint Zusanli (ST 36) and the route of the primo vessels starting from it. This specific PVS route runs along the perineurium of the sciatic nerve, the pia mater, and the arachnoid mater of the spinal cord to the brain. Thus, by injecting a suitable anticancer drug into ST 36, one can deliver the drug into the brain to treat gliomas and other brain tumors. This new drug-delivery method is just one of the new clinical applications that are possible by combining acupuncture and using the PVS. Conclusions: Anticancer drugs for glioma can be injected into the primo node at the acupoint ST 36 to reach the cancer tissue through the PVS in the sciatic nerve, spine, and brain that can avoid the blood-brain barrier. PMID- 26155318 TI - Nanoparticles for Radiation Therapy Enhancement: the Key Parameters. AB - This review focuses on the radiosensitization strategies that use high-Z nanoparticles. It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy. Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist. In particular, we described and evaluated the influence of X-rays energy spectra using a numerical analysis. We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy. Pointing out the critical parameters of high-Z nanoparticles radiosensitization, this review is expected to contribute to a larger preclinical and clinical development. PMID- 26155320 TI - Acupuncture for Neoplasms: An Update from the PubMed Database. AB - Background: The therapeutic mainstays of cancer remain surgery, radiotherapy, and chemotherapy. However, radiotherapy and chemotherapy are often associated with serious side-effects, such as nausea and vomiting. Acupuncture has been used widely to treat disorders in clinical practice for at least 3000 years. According to the National Institutes of Health (NIH) Consensus Statement, chemotherapy induced nausea and vomiting are suitable for acupuncture intervention. Objectives: The goal of this review is to analyze the applications of acupuncture for treating cancer and to look ahead at the potential advantages of acupuncture for patients with cancer. Materials and Methods: The PubMed database was searched for articles on acupuncture therapy and neoplasms. The different distributions of scientific papers were analyzed preliminarily. Results: The articles found showed that acupuncture was used to address various symptoms related to different types of cancer. Conclusions: The results of clinical trials in acupuncture have provided important clues in oncologic practice. The evidence suggests that acupuncture is a safe and effective therapy for managing cancer and treatment related symptoms, such as nausea and vomiting and fatigue caused by chemotherapy. As more evidence emerges, the potential advantages of acupuncture in tumor treatment will eventually be clear. PMID- 26155321 TI - Treatment of Lymphedema with Saam Acupuncture in Patients with Breast Cancer: A Pilot Study. AB - Background: Lymphedema is a troublesome complication affecting quality of life (QoL) in many women after breast-cancer treatment. Recent studies have suggested that acupuncture can reduce symptoms of lymphedema in breast-cancer survivors. Objectives: This was a pilot study. It was designed to assess the feasibility and the safety of acupuncture with the Saam acupuncture method for treating lymphedema in Korean patients after surgical therapy for breast cancer. Materials and Methods: This was a prospective, single-arm, observational pilot study using before and after measurements. The study was conducted at the East-West Medical Center at the Daegu Catholic University Medical Center, in Daegu, Korea. The subjects were 9 patients with breast cancer who presented with lymphedema of the upper limb ipsilateral to surgery. Saam acupuncture was administered 3 times per week for 6 consecutive weeks, for 30+/-5 minutes at each session.The primary outcome measure was severity of lymphedema as assessed by stages of lymphedema, a visual analogue scale (VAS), and by circumferential measurements of the upper extremity. The secondary outcome measure was QoL, which was assessed by a self administered questionnaire using the Short Form-36 questionnaire. Results: Acupuncture reduced severity of lymphedema significantly, as assessed by the VAS (P<0.001) as well as by circumferential measurements of the upper extremity. Four weeks after the final treatment, symptoms were not aggravated. SF-36 scores remained significant for health status at the end of treatment. Conclusions: The Saam acupuncture method appeared to provide reduction of lymphedema among women after they had undergone surgery for breast cancer. A randomized, controlled prospective study with a larger sample size is required to clarify the role of acupuncture for managing lymphedema in patients with breast cancer. PMID- 26155322 TI - Noninvasive Skin Tightening Treatment. AB - Noninvasive skin tightening has become one of the most common cosmetic aesthetic procedures being performed today. The use of radiofrequency devices for these procedures has been at the forefront of this trend for the past several years. Newer and more sophisticated radiofrequency devices are being brought to the market and presented here are the Venus Freeze and Venus Legacy. PMID- 26155323 TI - Clindamycin Phosphate 1.2%/Tretinoin 0.025% Gel for the Treatment of Acne Vulgaris: Which Patients are Most Likely to Benefit the Most? AB - Clindamycin phosphate 1.2%/tretinoin 0.025% gel is a topical combination formulation used once daily for the treatment of acne vulgaris, with approval in the United States for patients >12 years of age. Three 12-week, randomized, vehicle-controlled, pivotal trials included > 1,800 actively treated subjects. In addition, an open-label, 52-week study was also completed with 442 subjects enrolled. The skin tolerability, safety, and efficacy of clindamycin phosphate 1.2%/tretinoin 0.025% gel applied once daily is well-established based on data from pivotal studies and analyses in other subsequent publications including from pooled analysis of results from 4,550 subjects. This article discusses results from the pivotal 12-week, Phase 3 studies of clindamycin phosphate 1.2%/tretinoin 0.025% gel applied once daily in 845 subjects with mild, moderate, or severe facial acne vulgaris and differentiates patterns of therapeutic response using study endpoint successes defined as clear, almost clear, or at least a 2-grade improvement in the AV severity rating. PMID- 26155324 TI - Efinaconazole Topical Solution, 10%, for the Treatment of Mild and Moderate Toenail Onychomycosis. AB - OBJECTIVE: To evaluate efficacy, safety, and tolerability of efinaconazole topical solution, 10%, in patients with mild (<=25% nail involvement) and moderate (>25% nail involvement) toenail onychomycosis. METHODS: A subgroup analysis of patients, aged 18 to 70 years, randomized to receive efinaconazole topical solution, 10%, or vehicle from two identical multicenter, double-blind, vehicle-controlled, 48-week studies evaluating safety and efficacy. The primary endpoint was complete cure rate (0% clinical involvement of target toenail and both negative potassium hydroxide examination and fungal culture) at Week 52. RESULTS: Mycologic cure rates were similar in mild and moderate onychomycosis patients treated with efinaconazole (58.2% and 55.5%, respectively), but markedly different with vehicle (25.0% and 14.1%, respectively). The primary endpoint, complete cure, was achieved in 25.8 percent of mild onychomycosis patients and 15.9 percent of moderate onychomycosis patients compared to 11.3 and 2.7 percent, respectively, with vehicle (both P<0.001). Treatment success (percent affected target toenail <=10%) for efinaconazole was 65.7 and 40.7 percent, respectively, depending on disease severity. Adverse events associated with efinaconazole were local site reactions and clinically similar to vehicle. CONCLUSIONS: Once-daily efinaconazole topical solution, 10%, may provide a useful topical option in the treatment of mild-to-moderate onychomycosis. PMID- 26155325 TI - Comprehensive Treatment of Periorbital Region with Hyaluronic Acid. AB - The periorbital subunit is one of the first facial regions to show signs of aging, primarily due to volume depletion of the soft tissue and bony resorption. Surgical and office-based nonsurgical procedures form an important basis for periorbital rejuvenation. It is important to make a detailed clinical evaluation of the patient to indicate the most appropriate procedure to be performed. With the objective of showing a nonsurgical procedure for the rejuvenation of the periorbital area, the authors describe a technique of applying fillers in the upper and lower periorbital regions, paying attention to the anatomy of this facial region and the type of product to be used besides the expected results of the procedure and its possible adverse effects and complications. The nonsurgical rejuvenation of the periorbicular region with hyaluronic acid is a new and innovative technique. In the opinion of the authors, it is a great aesthetic impact area and consequently brings high satisfaction to patients. PMID- 26155327 TI - Lichenoid Reactions in Association with Tumor Necrosis Factor Alpha Inhibitors: A Review of the Literature and Addition of a Fourth Lichenoid Reaction. AB - In this manuscript, a clinical case of a patient treated with adalimumab for Behcet's disease develops lichen planopilaris. A variety of mucocutaneous lichenoid eruptions have recently been described in association with tumor necrosis factor alpha inhibitors. The authors briefly discuss the clinical and pathological presentation of lichen planopilaris as well as a potential pathogenesis of cutaneous adverse effects seen as the result of tumor necrosis factor alpha inhibitor therapy. They review all case reports of lichen planopilaris occurring on tumor necrosis factor alpha inhibitors and suggest its classification as a fourth recognized pattern on this therapy. PMID- 26155326 TI - Light-emitting Diodes: A Brief Review and Clinical Experience. AB - BACKGROUND: In the early 1990s, the biological significance of light-emitting diodes was realized. Since this discovery, various light sources have been investigated for their cutaneous effects. STUDY DESIGN: A Medline search was performed on light-emitting diode lights and their therapeutic effects between 1996 and 2010. Additionally, an open-label, investigator-blinded study was performed using a yellow light-emitting diode device to treat acne, rosacea, photoaging, alopecia areata, and androgenetic alopecia. RESULTS: The authors identified several case-based reports, small case series, and a few randomized controlled trials evaluating the use of four different wavelengths of light emitting diodes. These devices were classified as red, blue, yellow, or infrared, and covered a wide range of clinical applications. The 21 patients the authors treated had mixed results regarding patient satisfaction and pre- and post treatment evaluation of improvement in clinical appearance. CONCLUSION: Review of the literature revealed that differing wavelengths of light-emitting diode devices have many beneficial effects, including wound healing, acne treatment, sunburn prevention, phototherapy for facial rhytides, and skin rejuvenation. The authors' clinical experience with a specific yellow light-emitting diode device was mixed, depending on the condition being treated, and was likely influenced by the device parameters. PMID- 26155328 TI - Chemical Burn from Vinegar Following an Internet-based Protocol for Self-removal of Nevi. AB - "Natural home remedies" for nevi removal found on the Internet can be ineffective, or worse, dangerous. Children and teens, in particular, may be more likely to attempt self-treatment in order to avoid discussing their concerns with their parents. Here, the authors report a case of an adolescent who presented with a chemical burn after following an Internet-based protocol for nevi removal using apple cider vinegar. PMID- 26155329 TI - The Application of Micropipette Aspiration in Molecular Mechanics of Single Cells. AB - Micropipette aspiration is arguably the most classical technique in mechanical measurements and manipulations of single cells. Despite its simplicity, micropipette aspiration has been applied to a variety of experimental systems that span different length scales to study cell mechanics, nanoscale molecular mechanisms in single cells, bleb growth, and nucleus dynamics, to name a few. Enabled by micro/nanotechnology, several novel microfluidic devices have been developed recently with better accuracy, sensitivity, and throughput. Further technical advancements of microfluidics-based micropipette aspiration would have broad applications in both fundamental cell mechanics studies and for disease diagnostics. PMID- 26155330 TI - Combination of Autofluorescence imaging and salivary protoporphyrin in Oral precancerous and cancerous lesions: Non-invasive tools. AB - BACKGROUND: Normal and cancerous tissues have distinct auto-fluorescence properties because of differences in their biophysical and biochemical agents. Scientific evidences related to diagnostic fluorescence imaging for detection of oral precancerous and cancerous lesions are very limited. OBJECTIVES: The aim of this study was to find out potential relationships between serum, salivary and tissue protoporphyrin IX ( PX) levels in subjects with or without oral precancerous and cancerous lesions. Also , to find out diagnostic value of fluorescence imaging (VELscope(r) system , LED Dental Inc., White Rock, B.C.) and salivary protoporphyrin IX (PX) in oral precancerous and cancerous lesions. Furthermore this study attempts to find out diagnostic value of the combination of approaches of fluorescence imaging and salivary protoporphyrin for detection of oral precancerous and cancerous lesions. MATERIAL AND METHODS: The study sample comprised 3 test groups, with biopsy confirmed precancerous (leukoplakia and lichen planus) and cancerous lesions (squamous cell carcinoma) and one control group of 25 healthy individuals. To find out sensitivity and specificity, another 100 patients presenting for routine dental care were selected and clinical examinations were followed by fluorescence imaging and normal photography, which were finally confirmed by biopsy. The clinical and histopathogical examinations were done in conjunction with photography of the oral cavity using digital camera and fluorescence imaging. Serum, tissue and salivary protoporphyrin (PX) levels were measured. RESULTS: Using fluorescence imaging, oral cancerous and precancerous lesions showed deep purple to deep brown and dark green colour respectively, while normal tissues showed pale green colour in contrast. The PX levels in serum, salivary and tissues were significantly higher in precancerous and cancerous lesions as compared to normal healthy tissues. Salivary and serum PX levels were highly correlated in all groups. The sensitivity and specificity to the discrimination of precancerous and cancerous lesions from the healthy tissues were higher by combination approaches of salivary protoporphyrin X and VELscope(r) system as compared individual approach. CONCLUSIONS: Combination approach of salivary protoporphyrin X and VELscope(r) system are more sensitive and specific to discriminate precancerous and cancerous lesions from the healthy tissues as compared to individual approach. Further studies are required on large samples of oral precancerous and cancerous lesions to test sensitivity and specificity and thus validate the clinical applicability of fluorescence imaging in (pre)cancerous diagnostics. Key words:Fluorescence imaging, oral cancerous, precancerous, protoporphyrin IX, saliva. PMID- 26155331 TI - Oral health status among Iranian veterans exposed to sulfur mustard: A case control study. AB - BACKGROUND: Sulfur mustard (SM) is a chemical warfare agent that has been repeatedly used since World War I. SM has chronic and deleterious effects on different body organs such as lungs, skin and eyes. OBJECTIVES: To determine dental and oral health status of chemical victims of SM who were exposed to SM during the Iraqi-Iran war. MATERIAL AND METHODS: In this case-control study, 100 male subjects exposed to SM were chosen as cases, and 100 non-exposed volunteers were chosen as controls. These groups were selected randomly according to their referral number, and were matched regarding age. Collection of information was performed using Oral Health Assessment Form designed by the World Health Organization. Quantitative and qualitative data were compared between the groups using independent samples t-test and Chi-square test, respectively. RESULTS: There was a significant difference between the case and control groups with respect to the frequencies of oral candidiasis, pharyngeal erythema and/or hyperplasia, hairy tongue and reflux disease, being higher in the former group. There was also a positive association between the frequency of candidiasis and the percentage of disability; pharyngeal erythema and/or hyperplasia and use of salmeterol spray; and between hairy tongue and antibiotic use in the case group. CONCLUSIONS: Exposure to SM and the use of drugs for controlling long-term complications does not increase the risk of tooth decay, tooth loss, and intra and/or extra oral lesions in patients, but may be associated with increased incidence of oral candidiasis, pharyngeal erythema and/or hyperplasia, hairy tongue and reflux disease.samples of oral precancerous and cancerous lesions to test sensitivity and specificity and thus validate the clinical applicability of fluorescence imaging in (pre)cancerous diagnostics. Key words:Sulfur mustard, oral health, candidiasis. PMID- 26155332 TI - Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery. AB - BACKGROUND: Surgical removal of mandibular third molars results in some degree of post-operative pain, swelling and trismus. These can be controlled by proper administration of local anesthesia, careful bone removal, minimal trauma to adjacent soft tissues and administration of methylprednisolone and serratiopeptidase drugs. The aim of the present study was to compare the efficacy of methylprednisolone and serratiopeptidase in controlling post-operative pain, swelling and trismus after surgical removal of impacted mandibular third molars. MATERIAL AND METHODS: The subjects were divided into two groups of 50 patients each undergoing surgical removal of mandibular third molars. Group A was given methylprednisolone 4mg orally every 8th hourly and Group B was given serratiopeptidase 10 mg every 12th hourly orally. Post-operatively pain, swelling and trismus were evaluated at the end of 1st, 3rd and 5thday. RESULTS: The results of this study showed that methylprednisolone is an effective analgesic, while serratiopeptidase has moderate analgesic activity. Serratiopeptidase is more effective than methylprednisolone in controlling post surgical swelling and trismus. Hence combination of these two drugs would be very effective than individual drug when widespread post-operative sequelae are expected after surgical removal of impacted lower third molars. CONCLUSIONS: We conclude that methylprednisolone affords better pain relief while serratiopeptidase exerts better anti-inflammatory and anti-swelling effects in the post-operative period. Synergistic combinations of these two drugs would however prove to be more effective when extensive post-operative sequelae are expected. Key words:Methylprednisolone, serratiopeptidase, pain, swelling, trismus, third molar. PMID- 26155333 TI - Immunohistochemical expression of MMP-2 and MMP-8 in oral squamous cell carcinoma. AB - BACKGROUND: Matrix metalloproteinases (MMPs) are endopeptidases that can degrade extracellular matrix components and affect invasiveness and aggressiveness of oral squamous cell carcinoma (OSCC). The aim of this study was to examine the immunohistochemical expression of MMP-2 and MMP-8 in OSCCs in patients presenting at the Tertiary Health facility in Nigeria. MATERIAL AND METHODS: Formalin-fixed, paraffin-embedded (FFPE) OSCC samples diagnosed between the years 2010 and 2012 were used for his study. The FFPE were processed for MMP-2 and MMP-8 using the specifications of the manufacturer. Two investigators reviewed the slides scoring the pattern and intensity of staining as negative (0), weakly positive (+1), moderately positive (+2) and strongly positive (+3). The data were analysed using version 20 of the SPSS. The level of significance was set at P < 0.05. RESULTS: Twenty-five OSCC consisting of 14 (56%) males and 11 females (44%) were used. The mean age was 54.6 +/- 17.9 years. A higher proportion (100%) of poorly differentiated OSCC strongly expressed MMP-2 compared with the well differentiated and moderately differentiated OSSC. There was no significant difference in the expression of MMP-2 amongst the three grades of OSCC (X2 = 2.87; p= 0.17). Only 5 (20%) OSCC cases positively expressed MMP-8. Moderate expression of MMP-8 was only seen in well-differentiated OSCCs. CONCLUSIONS: This study showed that a higher proportion of poorly differentiated OSSC strongly expressed MMP-2. Eighty percent of cases that express MMP-8 were females and moderate expression of MMP-8 was seen only in well differentiated OSCC. Key words:Oral squamous cell carcinoma, MMP-2, MMP-8, immunohistochemistry. PMID- 26155334 TI - Prevalence of oral mucosal lesions in a brazilian military police population. AB - BACKGROUND: Data obtained from oral health surveys are very important for identifying disease-susceptible groups and for developing dental care and prevention programs. So, the purpose of the current article was to investigate the prevalence of oral mucosa lesions (OMLs) in a population of Brazilian police. MATERIAL AND METHODS: Interviews and oral cavity examinations were performed on a sample of 395 police officers who were randomly selected by the calibrated researcher. The number of individuals was obtained by a sample calculation using the finite population correction. The diagnostic criteria were based on the WHO (1997) criteria and adapted to Brazilian surveys. RESULTS: In total, 8.61% of the population presented some OML. Traumatic injuries and benign migratory glossitis (BMG) were the most prevalent lesions. CONCLUSIONS: The prevalence of potentially malignant disorders was lower than among the Brazilian population.The most prevalent lesion among the police officers was related to trauma. Patients dissatisfied with oral health had a higher risk of presenting OMLs. Key words:Mouth disease, mouth mucosa, military personnel, public health, oral pathology, oral leukoplakia. PMID- 26155335 TI - In vitro study of the apical microleakage with resilon root canal filling using different final endodontic irrigants. AB - BACKGROUND: Endodontic microleakage or microfiltration refers to the percolation of fluids and micro-organisms at the interface of the obturation material and the walls of the root canal system. The aim of this in vitro study was to compare apical microfiltration of Resilon root canal filling by employing three different final irrigant solutions. MATERIAL AND METHODS: 128 single-rooted teeth were employed. The crowns were sectioned horizontally at the cemento-enamel junction and instrumented with 5.25% sodium hypochlorite (NaOCl) and 17% EDTA gel to obtain an instrumented 040 apical caliber. An intermediate irrigation was performed with distilled water. The roots were then randomly assigned to three experimental groups with three different final irrigants: (A) 20% citric acid (CA); (B) 2% chlorhexidine digluconate (CHX); and (C) 5.25% NaOCl, plus two control groups (positive and negative). They were then dried, obturated with RealSealTM, and cleared by Robertson's technique. Apical microleakage was measured by the dye penetration method and assessed with a 4.5x stereomicroscope. Data were statistically analyzed by one way ANOVA and post hoc analysis for multiple comparisons. RESULTS: Mean and standard deviations for apical microleakage were: 2% CHX (0.24 mm +/- 0.22), 20% CA (0.25 mm +/- 0.20), and 5.25% NaOCl (0.87 mm +/- 0.32). Significant differences were reported among the group irrigated with NaOCl, CHX and CA (P<0.001). CONCLUSIONS: A higher rate of apical microleakage was observed when the final irrigation was performed with NaOCl whilst lower rates were reported for CHX and CA. Key words:Apical filtration, endodontic irrigation, resin-based sealers, adhesion, root canal filling. PMID- 26155336 TI - A comparison of different irrigation systems and gravitational effect on final extrusion of the irrigant. AB - BACKGROUND: The aim of this study was to compare manual needle irrigation (MNI), RinsEndo (RE), and passive ultrasonic irrigation (PUI), and assess the effect of gravity on extrusion from the apex in vitro. MATERIAL AND METHODS: The distobuccal roots of molars were used and the canals were instrumented up to F2. Teeth were mounted on models, which permitted visualization and manipulation of the apices for necessary procedures. The models were placed in articulator to simulate the jaw. Six groups (G) were formed as: G1, G2 and G3 represented mandibular positioning of teeth and were irrigated with MNI, RE, and PUI, respectively, while G4, G5, and G6 represented maxillary positioning of teeth and were also irrigated in same sequence. Prior to the final irrigation, 72 cube shaped foam pieces covered with aluminum foil were weighed and the values were recorded as the initial weights. The cubes were then placed on the apical part of each sample. Final irrigation was performed with distilled water and the cubes were weighed again to determine their final weight. Data were analyzed using Kruskal-Wallis and Mann-Whitney U post-hoc test (p<0.05). RESULTS: Irrespective of the irrigation technique used, the amount of irrigant extruded from the apex showed a statistically significant difference related to the effect of gravity (p<0.05). There was no statistically significant difference between irrigation methods (p>0.05). When the irrigation systems were compared to examine the effect of gravity, the significant difference was found between G2 and G5 (p<0.05). CONCLUSIONS: Within the limitations of this study, MNI and PUI were found to be reliable irrigation systems. Caution should be exercised when using RinsEndo. Key words:Final irrigation, manual needle irrigation, passive ultrasonic irrigation, RinsEndo. PMID- 26155337 TI - Classification of impacted mandibular third molars on cone-beam CT images. AB - BACKGROUND: Neurological involvement is a serious complication associated to the surgical removal of impacted mandibular third molars and the radiological investigation is the first mandatory step to assess the risk of a possible post operative injury to the inferior alveolar nerve (IAN). The aim of this study was to introduce a new radiological classification that could be normally used in clinical practice to assess the relationship between an impacted third molar and mandibular canal on cone beam CT (CBCT) images. MATERIAL AND METHODS: CBCT images of 80 patients (133 mandibular third molars) were independently studied by three members of the surgical team to draw a classification that could describe all the possible relationships between third molar and IAN on the cross-sectional images. Subsequently, the study population was subdivided according to this classification. The SPSS software, version 15.0 (SPSS(r) Inc., Chicago, Illinois, USA) was used for the statistical analysis. RESULTS: Eight different classes were proposed (classes 0-7) and six of them (classes 1-6) were subdivided in two subtypes (subtypes A-B). The distribution of classes showed a prevalence of buccal or apical course of the mandibular canal followed by lingual position and inter-radicular one. No differences have resulted in terms of anatomic relationship between males and females apart from a higher risk of real contact without corticalization of the canal when the IAN had a lingual course for female group. Younger patients showed an increased rate of direct contact with a reduced calibre of the canal and/or without corticalization. CONCLUSIONS: The use of this classification could be a valid support in clinical practice to obtain a common language among operators in order to define the possible relationships between an impacted third molar and the mandibular canal on CBCT images. Key words:CBCT, classification, inferior alveolar nerve, third molars. PMID- 26155338 TI - Magnitude and distribution of stresses in composite resin and sound dentine interface with mechanical retentions. AB - BACKGROUND: Adhesive systems are constantly subjected to mechanical and chemical stresses that negatively impact the integrity and durability of the dentine adhesive interface. Despite the lack of evidence to support or reject the clinical indication for mechanical retention, the potential further contribution of these preparations to the behavior of the composite resin-sound dentine bond has been rarely addressed. The authors evaluated by finite element analysis the effect of mechanical retention on the magnitude and distribution of stresses in a composite resin-sound dentin bonding interface when subjected to tensile and shear forces. MATERIAL AND METHODS: A three-dimensional model was created based on three cylindrical volumes representing the sound dentin, adhesive system, and composite resin. From this main model, two models were designed to simulate dentine bonding: 1) a model with no mechanical retention, which considered flat adhesion; and 2) a model with retention, which considered four hemispherical holes on the dentine surface. Both groups were subjected to linear static analysis under tensile and shear loading of 200N. RESULTS: At the model with retentions' bonding interface under tensile and shear loading, a concentration of Von Mises equivalent stress was observed within the retentions, with a reduction of those stresses on the bonding boundary surface. CONCLUSIONS: Additional mechanical retention increases the tensile strength of the sound dentin-composite resin bonding interface, promoting a decrease in the magnitude of the stresses and their redistribution under tensile and shear loading. Key words:Adhesion, composite resins, dentine, finite element analysis. PMID- 26155339 TI - Dentin wettability enhancement for three irrigating solutions and their effect on push out bond strength of gutta percha / AH Plus. AB - BACKGROUND: The aim of this study was to investigate the effect of wettability enhancement for 17% EDTA, 2.5% sodium hypochlorite and 7% maleic acid solutions on push out bond strength of gutta percha /AH Plus to root dentin. MATERIAL AND METHODS: One hundred and eight extracted single rooted human lower premolars were instrumented up to Protaper Universal F5 then irrigated with 3ml of 2.5% NaOCl after each file. Irrigants were prepared and a pilot study for determination of Tween 80 concentration yielding the lowest surface tension value in every solution was conducted. Samples were randomly divided into a control group and two experimental groups (17% EDTA and 7% Maleate), further split into eight subgroups (n=12), according to Tween 80 implementation sequence. Roots were obturated using gutta percha and AH plus by lateral condensation. Bond strength was measured by push out test. Mode of failure was then evaluated quantitatively by stereomicroscopy. Data were statistically analyzed using one way ANOVA followed by Tukey-Kramer for multiple comparisons. RESULTS: Control group showed the lowest values. Maleic acid subgroups showed significantly higher overall values than EDTA subgroups (P<0.05). Protocols implementing surfactant containing NaOCl showed significantly lower values than plain counterparts. Failure pattern was predominantly cohesive for plain regimens and the ones implementing Tween 80 in maleic acid solutions with plain NaOCl. CONCLUSIONS: Tween 80 addition to demineralizing irrigants increased the bond strength values. Surfactant containing NaOCl solutions yielded lower bond strength than plain ones. Key words:Wettability enhancement for three irrigants vs. corresponding gutta percha/AH Plus bonding. PMID- 26155340 TI - Dentin bond strength and degree of conversion evaluation of experimental self etch adhesive systems. AB - BACKGROUND: The aim of this study was to investigate the effect of different concentrations of 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) monomer in one-step self-etch experimental adhesives on dentinal microshear bond strength (uSBS), their degree of conversion and bonded micro structure. MATERIAL AND METHODS: Composite resin cylinders (Clearfil AP-X) were bonded on human sound molar dentinal surfaces by using five experimental one-step self-etching adhesives (1-SEAs) containing 0% (E0), 5% (E5), 10% (E10), 15% (E15), 20% (E20) (by weight) 10-MDP monomer and Clearfil S3 Bond (CS3) as a control. After 24 hours, microshear bond strength was tested. The degree of conversion was also measured using Fourier transform infrared spectroscopy. Interfacial ultrastructure was observed under a scanning electron microscope in all the groups. RESULTS: A higher microshear bond strength was observed with adhesives containing 10% and 15% 10-MDP in comparison to study groups (P<.05). Clearfil S3 Bond and 10% MDP had a significantly greater degree of conversion than other groups (P<.05). CONCLUSIONS: The amount of functional monomer in 1-SEAs influences both the bonding performance and degree of conversion; 10% 10-MDP showed the best combination of bond strength and degree of conversion. Key words:Self-etch adhesives, 10-MDP, bond strength, degree of conversion. PMID- 26155341 TI - Fracture resistance and failure mode of posterior fixed dental prostheses fabricated with two zirconia CAD/CAM systems. AB - BACKGROUND: In recent years there has been an improvement of zirconia ceramic materials to replace posterior missing teeth. To date little in vitro studies has been carried out on the fracture resistance of zirconia veneered posterior fixed dental prostheses. This study investigated the fracture resistance and the failure mode of 3-unit zirconia-based posterior fixed dental prostheses fabricated with two CAD/CAM systems. MATERIAL AND METHODS: Twenty posterior fixed dental prostheses were studied. Samples were randomly divided into two groups (n=10 each) according to the zirconia ceramic analyzed: Lava and Procera. Specimens were loaded until fracture under static load. Data were analyzed using Wilcoxon's rank sum test and Wilcoxon's signed-rank test (P<0.05). RESULTS: Partial fracture of the veneering porcelain occurred in 100% of the samples. Within each group, significant differences were shown between the veneering and the framework fracture resistance (P=0.002). The failure occurred in the connector cervical area in 80% of the cases. CONCLUSIONS: All fracture load values of the zirconia frameworks could be considered clinically acceptable. The connector area is the weak point of the restorations. Key words:Fixed dental prostheses, zirconium-dioxide, zirconia, fracture resistance, failure mode. PMID- 26155342 TI - Tannerella forsythia is associated with increased levels of atherogenic low density lipoprotein and total cholesterol in chronic periodontitis. AB - BACKGROUND: Accumulating evidence suggests that acute and chronic infections with periodontopathogens are associated with an increased risk of cardiovascular disease. The objective of this study was to assess whether Tanerella forsythia and Porphyromonas gingivalis are associated with increased levels of atherogenic low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol (TC), triglycerides and body mass index (BMI) in chronic periodontitis patients. MATERIAL AND METHODS: Medical history and clinical and radiographic examination were conducted in 80 chronic periodontitis patients and 28 healthy individuals. Fasting blood samples were drawn for the measurement of the parameters of dyslipidemia. Anthropometric measurements such as height in meters and weight in kilograms were recorded. Both periodontitis and control subjects were asked to answer a questionnaire with regard to their socio-demographic and smoking status. The presence of T. forsythia, and P. gingivalis was detected using primers designed to target the respective 16S rRNA gene sequences. RESULTS: The occurrence of T. forsythia and P. gingivalis was higher in the group of subjects with periodontitis. Superior levels of triglycerides were observed in chronic periodontitis patients compared to healthy individuals. High levels of TC in periodontitis persons were significantly associated with increased bleeding on probing. Greater mean levels of TC and LDL were shown in the presence of T. forsythia (P<0.05). Likewise, higher proportions of patients with BMI >=25 kg/m2 related with T. forsythia (P<0.05). T. forsythia was a significant discriminating factor in the multivariate linear regression model emerging as significant explanatory of increased levels of TC (beta=17,879, 95% CI = 4,357-31,401; p=0.01) and LDL (beta=17,162, 95% CI= 4,009-30,316; p=0.01). CONCLUSIONS: Higher levels of serum total cholesterol and LDL were observed in the occurrence of T. forsythia and the presence of this periodontopathogen may increase the atherogenic potency of low-density lipoprotein that may augment the risk for atherosclerosis in periodontal disease patients. Key words:Periodontitis, dyslipidemia, Tannerella forsythia, cardiovascular disease. PMID- 26155343 TI - Laser-Casein phosphopeptide effect on remineralization of early enamel lesions in primary teeth. AB - BACKGROUND: The aim of this study was to assess the effect of Nd:YAG laser irradiation following casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) application on calcium and phosphate concentration and surface microhardness (SMH) of enamel surface in artificial white spot lesions of primary teeth. MATERIAL AND METHODS: Eighty teeth with artificial white spot lesions were randomly divided into four groups: (A) distilled and deionized water, (B) Nd:YAG laser, (C) CPP-ACP creme, & (D) CPP-ACP plus laser. SMH was measured using Vickers diamond indenter in Vickers Hardness Number (VHN). Two samples of each group were analyzed using scanning electron microscope (SEM). The results were analyzed with the SPSS 17/win. RESULTS: The subjects of group D demonstrated a significant increase in the calcium and phosphate contents of enamel surface compared to those of groups A (P < 0.001, P < 0.001), B (P < 0.001, P < 0.001) and C (P = 0.024, P = 0.04), respectively. A statistically significant difference was seen for mean VHN between groups A and B (P = 0.002). SEM evaluations confirmed the results. CONCLUSIONS: The combination of Nd:YAG laser and CPP-ACP creme could be recommended as an effective preventive modality for remineralizing of white spot lesions in primary teeth. Key words:CPP-ACP, enamel remineralization, microhardness, Nd:YAG, primary teeth, SEM. PMID- 26155344 TI - The relationship between tooth size discrepancy and archform classification in orthodontic patients. AB - BACKGROUND: To determine the relationship between clinically significant tooth size discrepancies (TSD) and archform classification in orthodontic patients. MATERIAL AND METHODS: Eighty teeth with artificial white spot lesions were randomly divided into four groups: (A) distilled and deionized water, (B) Nd:YAG laser, (C) CPP-ACP creme, & (D) CPP-ACP plus laser. SMH was measured using Vickers diamond indenter in Vickers Hardness Number (VHN). Two samples of each group were analyzed using scanning electron microscope (SEM). The results were analyzed with the SPSS 17/win. RESULTS: Reproducibility of the classification of archform was very good (unweighted Kappa statistic of 0.83 with a 95% confidence interval of 0.73, 0.93). There was no statistically significant difference in the distribution of archform type between group 1 and group 2 for the upper (p=0.3305) or lower (p=0.6310) arches. CONCLUSIONS: The presence of a clinically significant TSD and archform classification do not appear to be related. Key words:Tooth Size, Archform, Bolton discrepancy, digital models, polynomial curve, archform classification. PMID- 26155345 TI - Dentofacial abnormalities among adolescents: A study on the prevalence and severity. AB - BACKGROUND: The objectives of this investigation were to assess prevalence and severity of dentofacial abnormalities and orthodontic treatment need among adolescents in Mangalore taluk. MATERIAL AND METHODS: A cross-sectional study was conducted among 1340 children from randomly selected high schools. A proforma was used to record demographic data and components of the Dental Aesthetic Index [DAI] for each subject. The Chi squared test was used for analysis with p-value of < 0.05 considered statistically significant. RESULTS: Dentofacial abnormalities (DAI scores >= 26) were recorded in 38.5% subjects. Mean DAI score of the study population was 24.59 +/- 6.09. Female subjects presented with higher prevalence and higher mean DAI scores than their male counterparts (p > 0.05). Assessment of severity of malocclusion between age groups revealed no differences (p > 0.05). Orthodontic treatment was highly desirable in 11% and mandatory in 5.2% subjects. CONCLUSIONS: A high prevalence of dentofacial abnormalities was found among adolescents in Mangalore taluk pointing towards a need for designing effective programs for early diagnosis and treatment of this condition, especially among adolescents. Key words:Adolescents, Dental Aesthetic Index [DAI], dentofacial abnormalities, malocclusion, orthodontic treatment need, prevalence, severity. PMID- 26155346 TI - Post-fatigue fracture resistance of metal core crowns: press-on metal ceramic versus a conventional veneering system. AB - BACKGROUND: The aim of this in vitro study was to compare the mechanical failure behavior and to analyze fracture characteristics of metal ceramic crowns with two veneering systems - press-on metal (PoM) ceramic versus a conventional veneering system - subjected to static compressive loading. MATERIAL AND METHODS: Forty-six crowns were constructed and divided into two groups according to porcelain veneer manufacture. Group A: 23 metal copings with porcelain IPS-InLine veneering (conventional metal ceramic). Group B: 23 metal copings with IPS-InLine PoM veneering porcelain. After 120,000 fatigue cycles, the crowns were axially loaded to the moment of fracture with a universal testing machine. The fractured specimens were examined under optical stereomicroscopy and scanning electron microscope. RESULTS: Fracture resistance values showed statistically significant differences (Student's t-test) regarding the type of ceramic veneering technique (p=0.001): Group A (conventional metal ceramics) obtained a mean fracture resistance of 1933.17 N, and Group B 1325.74N (Press-on metal ceramics). The most common type of fracture was adhesive failure (with metal exposure) (p=0.000). Veneer porcelain fractured on the occlusal surface following a radial pattern. CONCLUSIONS: Metal ceramic crowns made of IPS InLine or IPS InLine PoM ceramics with different laboratory techniques all achieved above-average values for clinical survival in the oral environment according to ISO 6872. Crowns made with IPS InLine by conventional technique resisted fracture an average of 45% more than IPS InLine PoM fabricated with the press-on technique. Key words:Mechanical failure, conventional feldspathic, pressable ceramic, chewing simulator, thermocycling, compressive testing, fracture types, scanning electron microscope. PMID- 26155347 TI - Lip and oral lesions in children with Down syndrome. A controlled study. AB - BACKGROUND: Down syndrome (DS) is the most common chromosomal abnormality affecting numerous organs, including the orofacial region. The objective of the present study was to assess the prevalence of lip and oral soft tissue lesions, with particular emphasize on the incidence of fissured tongue, lip fissures and angular cheilitis, among individuals with DS in Yemen. MATERIAL AND METHODS: This controlled cross-sectional study included 50 children with DS (6-18 years), and 50 age-and gender-matched healthy controls. The prevalence of orofacial soft tissue lesions was evaluated in both groups. Data were analyzed by Chi-square and Fisher tests, and p < 0.05 was considered to be statistically significant. RESULTS: Ten orolabial lesions were identified among the subjects. The most frequently seen lesions were: Fissured tongue (78.0%), lip fissures (64.0%), angular cheilitis (38.0%) and Cheilitis (14.0%). The frequencies of these lesions were significantly higher in children with DS than healthy controls (P< 0.001). Most of lip fissures were in the lower lip, and 80% of the fissures were in the midline. CONCLUSIONS: The prevalence of lip and oral lesions among individuals with DS is remarkably high. Hence, oral physicians should be more aware of the orofacial findings seen more frequently in this genetic disorder. Key words:Down syndrome, lesions, lips, oral. PMID- 26155348 TI - Toxicity test of a dental commercial composite. AB - BACKGROUND: International rules must be followed for testing biosecurity in dental materials. A new brand of restorative material appeared in the market and regulations indicated that it should be tested for toxicity. OBJECTIVES: The aim of this study was to determine the 90-day sub chronic toxicity of one triethylene glycol dimethacrylate containing composite (MEDENTAL Light-Cure CompositeTM) orally administered to rats according to Organization for Economic Co-Operation and Development no. 48 guidelines and the requirements specified in the ISO 10993 11. MATERIAL AND METHODS: Wistar rats ate the polymerized composite during 90 days and were observed to determine changes in their behavior, eye and skin signs and other attitudes such as aggressiveness, posture, walking and response to handling. After 90 days were sacrificed to ascertain blood alterations, we did special hematological tests and assessed microscopic slides from 33 different organs. RESULTS: We recorded no significant changes in clinical behavior of the animals. Microscopic review of the H&E stained slides obtained from the analyzed organs showed no abnormal inflammatory or cytological changes and all hematological special tests were within normal limits. CONCLUSIONS: Results of this study show that under our experimental conditions the MEDENTAL Light-Cure CompositeTM does not produce inflammatory or cytological changes suggestive of toxicity. Key words:Dental materials, composite resin, toxicity, inflammation, TEGDMA. PMID- 26155349 TI - Case-control study of craniomandibular disorders in patients with fibromyalgia. AB - BACKGROUND: Fibromyalgia is a clinical syndrome characterized by chronic widespread pain, which is non-articular and is predominantly experienced in the muscles and vertebral column, and by extensive heightened sensitivity to local pressure at many specific points The purpose of this study was to measure differences in the level of painful symptoms and in the movements of the mandible in a group of patients who had been diagnosed as suffering from fibromyalgia, in comparison with a control group. The anxiety and subjective pain levels and their relation with mandibular mobility were also compared. MATERIAL AND METHODS: A case-control study was designed. The temporomandibular joints and masticatory muscles of the cases (n=20) and controls (n=18) were examined, anxiety was assessed by the STAI index and subjective pain was measured on a visual analogue scale. The data analysis was carried out with SPSS v.19.0 software. The descriptive data were expressed as means and proportions at a 95% confidence interval. The proportions were compared with the chi-square test and the means with the Mann-Whitney U test. Pearson's correlation coefficient was used to measure the association between quantitative variables. RESULTS: The fibromyalgia patients (the case group) presented a higher level of pain following the musculoskeletal examination and significantly greater symptoms at the examination points. Regarding joint mobility, significant differences in mandibular opening were found (cases 43.4 mm vs controls 47.2 mm, p = 0.042). The mean pain score of the cases was significantly higher than that of the controls (4.03 vs 1.8, p = 0.001) but no significant differences were found in the anxiety index (23.8 vs 23.4). CONCLUSIONS: patients with fibromyalgia are affected to a greater extent by craniomandibular disorders, with lower mouth opening and higher pain levels than healthy persons. However, the anxiety levels of the two groups are similar. Key words:Fibromyalgia, orofacial pain, temporomandibular disorder. PMID- 26155350 TI - Measurement of the percentage of root filling in oval-shaped canals obturated with Thermafil Obturators and Beefill 2in1: In vitro study. AB - BACKGROUND: The aim of the study was to measure the percentage of root canal fillings in long oval canals obturated with thermoplasticized gutta-percha techniques, Beefill 2in1(r) and Thermafil Obturators(r). MATERIAL AND METHODS: Fifty four mandibular incisors were selected after bucco-lingual and mesio-distal radiographs showed at 5 mm from apex an internal long:short diameter >=2. Teeth were instrumented with Protaper Universal and divided in two groups of 27. Group 1 was obturated with Thermafil Obturators(r) and group 2 with Beefill 2in1(r). Two horizontal sections were cut at 5 and 7 mm from the apex and photographed in a stereo-microscope. The total area of the canal and filled canal in cross sections were measured with AutoCad and the percentages of gutta-percha-sealer and voids in the canal were obtained. RESULTS: Both systems achieved high percentage of filled canal, Thermafil 96.8% and Beefill 2in1 98.9%. The percentages of voids in both groups were very low. No significant differences were found between the two groups . The percentage obtained at 5 and 7 mm from the apex in both groups showed no significant difference. CONCLUSIONS: The percentages of filled canal (gutta-percha-sealer) were high and these two thermoplasticized techniques are suitable for long oval canals obturation. Key words:Long oval canal, oval canal, thermoplasticized obturation. PMID- 26155351 TI - Comparison of the therapeutic effects of the dietary and topical forms of Zizyphus jujuba extract on oral mucositis induced by 5-fluorouracil: A golden hamster model. AB - BACKGROUND: Oral mucositis (OM) is a common inflammatory complication among cancerous patients as an adverse effect of chemotherapy and radiotherapy. The aim of this study was to evaluate the effects and identify the appropriate route of administration of extract of Zizyphus jujuba in 5-flurouracile induced OM induction in golden hamster. MATERIAL AND METHODS: In a prospective randomized double blind animal study, OM was induced in 56 male golden hamsters by 5-FU (60 mg/kg) on days 0, 5, and 10 of the study. The cheek pouch was scratched with a sterile needle on once daily on days 3 and 4. On days 14-17, 300 mg/kg dietary and 20% Z. jujuba gel and gel base groups were treated and then compared with a control group. Microscopic scores and pouch content of malondialdehyde (MDA), plus activities of superoxide dismutase and myeloperoxidase in pouch tissue were evaluated. RESULTS: Histopathology scores of mucositis were lower in the systemic and 20% Z. jujuba gel groups than the gel base and control groups (P<0.05). Also, lower MDA level and higher activities of MPO and SOD were detected in the systemic and 20% Z. jujuba gel groups in comparison to the gel base and control groups (P<0.001). CONCLUSIONS: The use of Z. jujuba hydroalcoholic extract in systemic and topical forms may be associated with reduced intensity of OM, diminished concentration of MDA, and increased activity of MPO and SOD on induced OM in golden hamster undergoing 5-FU consumption. Key words:Oral mucositis, 5 flurouracil, Zizyphus jujube, oxidative stress, histopathology score. PMID- 26155352 TI - Investigating activity of masticatory muscles in patients with hypermobile temporomandibular joints by using EMG. AB - BACKGROUND: Temporomandibular joint hypermobility (TMJH) can manifest higher range of motions in mandible. The aim of this study was to investigate and compare the activity of masticatory muscle of TMJs in healthy individuals and patients with mild, moderate and severe TMJH. MATERIAL AND METHODS: In this clinical study, 69 patients (between the ages of 22 to 42) with manifestation of TMJH were included. The patients were divided into three groups based on their maximum mouth opening (MMO): (light) with MMO of 50-55 mm; (moderate) with MMO between 55 to 65 mm; and (severe) with MMO >65 mm. Also, 20 healthy people with profiled tomography in the last 6 months were invited as control group (healthy) with normal MMO (<50 mm). All the groups subjected to electromyogram (EMG) in 2 steps: maximal voluntary clenching (MVC) of the jaws; and during chewing of bread by using one side of the jaws voluntary. The collected data were analyzed by Student T-test and Chi-Square tests using SPSS software version 15 at significant level of 0.05. RESULTS: Both TMJs of light, moderate and severe groups showed significant differences in frequency, time of activity and rest in comparison with healthy group during chewing and MVC (all p values < 0.01). CONCLUSIONS: Masticatory muscles activity reduced in relation with the severity of TMJH and higher excessive mouth opening. Key words:Electromyography, joint hypermobility, mouth opening, tempormandibular joint. PMID- 26155353 TI - Indirect sinus lift without bone graft material: Systematic review and meta analysis. AB - A systematic literature review and a meta-analysis of indirect sinus lift without the use of bone graft material was performed. A PubMed search was made from January 2005 to January 2012 with keywords: "sinus lift", "osteotome", "graft" and "maxillary sinus elevation". The inclusion criteria were: maxillary sinus lift technique with osteotomes with a minimum follow-up period of 5 months after surgery without bone graft material. 11 articles were included. The mean gain in residual crestal bone height after maxillary sinus lift without bone graft material was 3,43 mm +/- 0,09 (2,5 mm - 4,4 mm). The survival rate ranged from 94% to 100%. Placement of implants with sinus lift without bone graft material, is a valid surgical technique to gain residual crestal height and placed implants in an atrophic posterior maxillary with a crestal height from 5 to 9 mm. Key words:Sinus lift, osteotome, graft, maxillary sinus elevation. PMID- 26155354 TI - Influence of orthodontic treatment on temporomandibular disorders. A systematic review. AB - OBJECTIVES: The aim of this literature systematic review was to evaluate the possible association between malocclusions, orthodontic treatment and development of temporomandibular disorders. MATERIAL AND METHODS: A search was carried out on PubMed-Medline database from January 2000 to August 2013 using the keywords "orthodontics and temporomandibular disorders", "orthodontics and facial pain" and "malocclusion and temporomandibular disorders". Human studies included in the study were those assessing signs and symptoms of temporomandibular disorders in relation to orthodontic treatment. MATERIAL AND METHODS: A search was carried out on PubMed-Medline database from January 2000 to August 2013 using the keywords "orthodontics and temporomandibular disorders", "orthodontics and facial pain" and "malocclusion and temporomandibular disorders". Human studies included in the study were those assessing signs and symptoms of temporomandibular disorders in relation to orthodontic treatment. RESULTS: The search strategy resulted in 61 articles. After selection according to the inclusion/exclusion criteria 9 articles qualified for the final analysis. The articles which linked orthodontics and development of temporomandibular disorders showed very discrepant results. Some indicated that orthodontic treatment could improve signs and symptoms of temporomandibular disorders, but none of them obtained statistically significant differences. CONCLUSIONS: According to the authors examined, there is no evidence for a cause-effect relationship between orthodontic treatment and temporomandibular disorders, or that such treatment might improve or prevent them. More longitudinal studies are needed to verify any possible interrelationship. Key words:Malocclusion and temporomandibular disorders, orthodontics and facial pain, orthodontics and temporomandibular disorders, temporomandibular disorders, temporomandibular dysfunction. PMID- 26155355 TI - Pathological mandibular fracture: A severe complication of periimplantitis. AB - Nowadays, dental implant treatment is a very common option for patients even in medical compromised conditons. Some complications related to them have been described. Periimplantitis (PI) is one of the biggest concerns complications of these kind of treatments, probably has a multifactorial aethiology. Usually the consequences of PI are the loss of the implants and prostheses, expenses of money and time for dentists and patients. Very often PI implies the necesity of repeating the treatment . Pathological mandibular fracture due to PI is a severe but infrequent complication after dental implant treatment, especially after PI. In this study we present three cases of mandibular pathologic fractures among patients with different medical and dental records but similar management: two of them had been treated years ago of oral squamous cell carcinoma with surgery and radiotherapy, the other patient received oral bisphosphonates for osteoporosis some years after implantation. We analized the causes, consequences and posible prevention of these fractures as well as the special features of this kind of mandibular fractures and the different existing treatments. Key words:Periimplantitis, pathological mandibular fracture, mandibular atrophy, bicortical implants. PMID- 26155356 TI - Mucormycosis in a healthy elderly patient presenting as oro-antral fistula: Report of a rare incidence. AB - Mucormycosis is a rare opportunistic fungal infection that commonly affects patients who are immuno-compromised. It invariably presents as an acute spreading infection, with very poor prognosis if not treated promptly. We report a case of mucormycosis in immuno-competent elderly patient, presenting as oro-antral communication. Patient's history, clinical and laboratory evaluation revealed no systemic predisposing factors. The disease was non-fulminant, localized and showed remission after local measures, without parentral anti-fungal therapy. Key words:Mucormycosis, maxilla, elderly, oroantral communication. PMID- 26155357 TI - Hand, foot and mouth disease - a short case report. AB - Hand, foot and mouth disease, that was once considered a disease of cattle, has been emerging as a common human childhood disease in the last few years. It is a viral disease characterized by a brief febrile illness and typical vesicular rashes. In rare cases, patients may also develop neurological complications. This report describes a case of hand, foot and mouth disease, presented with typical clinical features in the South Indian region. Key words:Hand, foot and mouth disease, viral lesions, blisters. PMID- 26155358 TI - Alternative surgical management of oroantral fistula using auricular cartilage. AB - One of the clinical complications encountered by oral and maxillofacial surgeons is oroantral communication (OAC) with subsequent formation of oroantral fistula (OAF). Many techniques and treatment modalities have been described for the management of OAC and OAF. There are advantages and disadvantages of all these techniques. We report a 21-year-old male patient who was admitted to our department for the presence of an OAF and was treated using an auricular cartilage graft. This technique may be useful to treat OAF and to provide a solid alveolar bone site for subsequent pre-implant surgery. Key words:Auricular cartilage, implant surgery, oroantral fistula. PMID- 26155359 TI - Sunct syndrome. Report of a case and treatment update. AB - Short-lasting unilateral neuralgiform headache attacks with conjuntival injection and tearing (SUNCT) is considered a rare trigeminal autonomic cephalgias, a group of primary headache disorders characterized by brief episodes of severe unilateral headache in the distribution territory of the trigeminal nerve, accompanied by prominent ipsilateral and cranial parasympathetic autonomic features. The present report describes a SUNCT syndrome in a 64-year-old male who had been diagnosed with trigeminal neuralgia several years ago. The patient reported stabbing pain in the orbital zone and in the left upper maxillary region, of great intensity, brief duration, and a frequency of 20-100 attacks a day. Pain episodes were accompanied by conjunctival injection and tearing. Based on the anamnesis, clinical examination and a magnetic resonance imaging scan, episodic SUNCT syndrome was diagnosed and pharmacological treatment with topiramate was started. This reduced the intensity and number of attacks to 3-6 a day. Key words:Trigeminal autonomic cephalgias, SUNCT, Cluster headache, topiramate. PMID- 26155360 TI - Incarceration of the hepatic lobe in incisional hernia: A case report. AB - INTRODUCTION: Incisional hernias are abnormal peritoneal outward pouch-like protrusions that develop due to defects that arise as a result of the disruption of the fascia's continuity after abdominal surgery. PRESENTATION OF CASE: A 77 year-old female patient presented to the emergency department of our hospital with complaints of abdominal swelling, abdominal pain, nausea and vomiting. The patient was recommended for surgery. It was decided that the primary fascia closure and onlay patch was the most appropriate approach. DISCUSSION: When the defect in the abdominal wall grows, the functionality of the related abdominal wall is disrupted thereby eliminating the dynamic structure of the abdominal wall. Incisional hernias lead to a significant number of job losses and morbidity and negatively affect quality of life. Moreover, the formations in the hernia pouch might lead to higher risk of strangulation and dysfunction. CONCLUSION: Subcutaneous herniation of the left lobe of the liver passing through the abdominal wall is a very rare condition. PMID- 26155361 TI - Efficiency of herbal medicine Dai-kenchu-to on portal blood flow in rat models. AB - INTRODUCTION: To clarify the influence of Dai-Kenchu-To (DKT) on portal blood flow (PBF), PBF was continuously measured with Doppler ultrasound. METHODS: Normal liver rats were divided into a DKT 90 mg/kg, DKT 270 mg/kg administered group, and control, while cirrhotic liver rats were divided into a DKT-LC 90 mg/kg administered group and Control-LC. The PBF was measured after the administration of either DKT or water for 60 min by laser Doppler flowmetry system. RESULTS: The PBF in the DKT 90 increased approximately 10 min after DKT was administrated, and elevated levels were maintained for approximately 10 min. A comparison of the increase in PBF by the calculating the area under the curve (AUC) revealed that flow was significantly higher in the DKT 90 compared to either the control or the DKT 270 (p < 0.05). The cirrhotic liver group showed stable PBF in both the DKT-LC and Control-LC. The AUC, revealed no significant difference between the DKT-LC and Control-LC. DISCUSSION: DKT induced an increase in PBF in normal livers; however, its effects were insufficient to increase PBF in the cirrhotic livers. No increase in the portal blood flow in the cirrhotic liver rats was probably the result of the cirrhotic liver, which had fibrotic change, and, therefore, may not have had sufficient compliance to accept the increasing blood flow volume from the intestinal tract. CONCLUSION: We suggested DKT has the potential to protect the liver by increasing PBF when the liver has either normal or mild to moderate dysfunction. PMID- 26155362 TI - Lower extremity necrotizing fasciitis: A unique initial presentation of Crohn's disease. AB - Crohn's disease is a disease of the bowel, typically presenting with diarrhea, weight loss, and abdominal pain. Complications such as abscesses, fistulas, and strictures may require surgical intervention. We would like to report a patient with Crohn's disease who presented for the first time with left lower extremity necrotizing fasciitis. There are very few reports of necrotizing fasciitis in Crohn's disease as the initial presentation. PMID- 26155363 TI - Tumor-induced osteomalacia due to a recurrent mesenchymal tumor overexpressing several growth factor receptors. AB - Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. These tumors typically follow a benign clinical course and local recurrence occurs in <5% of cases. We investigated a 49 year-old man with a recurrent mesenchymal phosphaturic tumor showing no signs of malignancy. The patient suffered from chronic muscle weakness, myalgia and cramps. His medical record included the diagnosis of oncogenic osteomalacia, for which he was submitted to tumor resection in the left leg three times before. Laboratory examination showed hypophosphatemia, hyperphosphaturia and an elevated serum FGF23 level. A radical surgical approach (amputation) was advised, however, complete biochemical and clinical remission was not reached. Molecular analysis of the tumor cells demonstrated overexpression of growth factor receptors implicated in tumor angiogenesis and metastatic potential (platelet derived growth factor type A (PDGFRA), PDGFRB and vascular endothelial growth factor receptor) together with increased expression of FGF23, x-linked-phosphate regulating endopeptidase and KLOTHO. TIO is usually associated with benign phosphauturic tumors and, when identified, resection of the tumor leads to complete remission in the majority of cases. The underlying pathophysiology of recurrences in these tumors is not known. This is the first report showing increased expression of growth factor receptors in a locally aggressive but histopathologically benign phosphaturic mesenchymal tumor. LEARNING POINTS: TIO is usually associated with benign soft tissue or bone neoplasms of mesenchymal origin.These tumors typically follow a benign clinical course and even in the rare malignant cases local recurrence occurs in <5%.Successful identification and removal of the tumor leads to full recovery in the majority of cases. PMID- 26155365 TI - A short-term evaluation of the safety and the efficacy of bipolar transurethral resection of the prostate in patients with a large prostate (>90 g). AB - OBJECTIVE: To evaluate the efficacy and safety of bipolar transurethral resection of the prostate (TURP) in patients with a large prostate (>90 g), as a significant recent modification of TURP is the incorporation of bipolar technology, which uses the same technique as monopolar TURP but with normal saline as the irrigant. PATIENTS AND METHODS: Forty patients with a prostate of >90 g and who were considered at risk for monopolar TURP were treated by bipolar TURP. The operative duration, resection time, resected tissue weight, resection rate, resection ratio, amount of irrigation fluid used, the decrease in intraoperative haemoglobin level, haematocrit and serum sodium levels, and the blood loss were recorded. The follow-up data were analysed. RESULTS: The mean (SD) operative duration was 116.3 (25.52) min, the resection time was 106.5 (25.69) min, the resected volume was 78.9 (20.58) g, the decrease in haemoglobin levels was 1.67 (0.46) g/dL, the mean serum sodium decline was 2.60 (0.68) mmol/L, and the blood loss was 532 (101.2) mL. The blood loss/g of resected tissue was 6.85 (0.70) mL. The mean (SD) postoperative bladder irrigation time was 2.0 (0.32) days, the catheterisation time was 3.25 (0.55) days and the postoperative hospital stay was 3.25 (0.55) days. CONCLUSION: Bipolar technology makes it possible to use TURP to treat patients with very large prostates and who are at risk when treated by the standard monopolar technology, with a satisfactory safety profile and with favourable efficacy. PMID- 26155366 TI - The Clinical Relevance of Various Hypersensitivity Tests in Patients with Atopic Dermatitis as Assessed by Their History, SCORAD Changes, and Number of Days with Need of Anti-Inflammatory Treatment. AB - Immediate and delayed hypersensitivity reactions can play a role in the pathogenesis of atopic dermatitis (AD). We tested 71 patients (median age 5 years) with AD for hypersensitivity to grass and birch pollen, Dermatophagoides pteronyssinus, and Dermatophagoides farinae using atopy patch test (APT), skin prick test (SPT), and specific IgE measurement. The sensitivity (SE) and specificity (SP) of the tests were calculated on the basis of personal history of AD exacerbation, clinical AD score (SCORAD) changes, and the number of days with need for topical anti-inflammatory treatment (AITD) in relation to exposure to the allergens being tested. APT was positive in 45 patients, mostly to D. farinae (n=37). SPT and/or specific IgE were positive in 42 subjects, in most cases to grass and birch pollen (n=29). SE of APT reached 33%-56% for history, 33% for SCORAD, and 0%-60% for AITD; SP of APT was comparable for all three assessment standards (history, SCORAD, and AITD) (48%-67%). SE of SPT/specific IgE was higher for history (26%-63%) than for the other two standards of assessment (0% 67%); SP of SPT/specific IgE was also highest for history (69%-91%), and lower for SCORAD (59%-87%) and AITD (65%-80%). AD is often associated with hypersensitivity; its influence on AD, however, is clinically significant only in a minor group of patients. While personal history and SCORAD changes present themselves as possible standards in the evaluation of clinically relevant hypersensitivity in AD patients, the anti-inflammatory treatment days (AITD) appears to be unsuitable for this purpose. PMID- 26155367 TI - Identification of IL13 C1923T as a Single Nucleotide Polymorphism for Asthma in Children from Mauritius. AB - Background: Research increasingly suggests that asthma is a familial and hereditary disorder and that genetic and environmental factors play a key role in its pathogenesis. Objective: The aim of this study was to investigate the associations between 10 single nucleotide polymorphism (SNP) loci in the development of asthma in children from the Mauritian population. Methods: The study population consisted of 193 children with asthma and 189 healthy controls from the Mauritian population. Asthma was diagnosed in accordance with the American Thoracic Society criteria. TaqMan real-time quantitative polymerase chain reaction was used to detect the genotypes of the SNP loci. Results: No statistically significant differences (p>0.05) were found between the experimental and control group in genotype distribution among nine of the loci (MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA Q551R, IL4RA I75V, IL4 C-590T, IL13 A2044G, IL13 C-1112T, and CHI3L1 C-131G). However, the frequency of IL13 C1923T TT in the asthma group was significantly higher than in the control group (odds ratio=2.119, p=0.033) suggesting that carriers of IL13 C1923T TT in the Mauritian population may have a more significant risk of developing asthma. Conclusion: The nine loci have little contribution to the development of childhood asthma in the Mauritian population. IL13 C1923T TT has been detected to be the susceptible genotype and may have a significant effect on the pathogenesis of childhood asthma in the Mauritian population. PMID- 26155368 TI - Relationship Between Serum Interleukin-17F Level and Severity of Atopic Dermatitis in Children. AB - Background: Recent discovery of the Th17 pathway is providing new opportunities for understanding chronic immune-mediated diseases. The Th17 pathway has been historically associated with chronic inflammatory diseases such as psoriasis, multiple sclerosis, and rheumatoid arthritis. Among Th17 cytokines, pathogenic roles of IL-17A and IL-17F in asthma have been well described. Recently, the number of peripheral blood Th17 cells was found to correlate with disease severity in patients with atopic dermatitis (AD). This study aimed to investigate serum IL-17F levels in children with AD and to correlate this with severity of the disease. Methods: Enzyme-linked immunosorbent assay was used to measure IL 17F levels in the sera of 228 patients with AD and 62 control children. The SCORing Atopic Dermatitis (SCORAD) tool was used to determine the severity of disease. Results: The mean serum level of IL-17F in children with AD was significantly higher than that in the control group (p<0.05) Serum IL-17F levels were also higher in patients with severe AD than in those with mild AD (p<0.001), and IL-17F levels and SCORAD scores were positively correlated (p<0.05). Conclusions: Serum IL-17F level might be a useful marker in children with AD. PMID- 26155369 TI - Respiratory Severity Score Separates Upper Versus Lower Respiratory Tract Infections and Predicts Measures of Disease Severity. AB - Background: A respiratory severity score (RSS) describing acute respiratory illness (ARI) severity would be useful for research and clinical purposes. Methods: A total of 630 term infants presenting with ARI had their RSS measured. Results: RSS was higher in those with lower respiratory tract infection (LRTI) compared with those with upper respiratory infection (URI; LRTI 6.5 [4-8.5]; URI 1 [0-2], p<0.001) and in hospitalized infants compared with outpatients (hospitalized 6.5 [4-9]; outpatient 1 [0-3], p<0.001). Conclusions: RSS is higher in LRTI compared with URI and in hospitalized compared with nonhospitalized infants. PMID- 26155370 TI - Development of a Tool to Evaluate Asthma Preparedness and Management in Child Care Centers. AB - Introduction: Asthma is a common condition affecting many children in child-care centers. The National Asthma Education and Prevention Program offers recommendations about creating an asthma-friendly child-care setting. However, no studies have investigated the extent to which child-care centers adhere to these recommendations. This study describes the development of a novel instrument to determine the ability of child-care centers to meet national recommendations for asthma. Methods: The Preparing for Asthma in Child Care (PACC) Instrument was developed using information from existing recommendations and standards, the peer reviewed literature, site visits, and expert interviews. The survey questions were pilot-tested at 36 child-care centers throughout San Francisco. Results: The instrument is composed of 43 items across seven domains: smoking exposure, presence of a medical consultant and policies, management of ventilation and triggers, access to medication, presence of asthma action plans, staff training, and encouragement of physical activity. Discussion: The PACC Instrument is an evidence-based and comprehensive tool designed to identify areas to target to improve asthma care for children in child-care centers. PMID- 26155371 TI - Comparing Injection Site Pain with Paliperidone Palmitate Versus First-Generation Depot Antipsychotics in Subjects with Schizophrenia. PMID- 26155372 TI - Sexual Dysfunction and Depression in Individuals with Multiple Sclerosis: Is there a Link? PMID- 26155373 TI - Effects of Escitalopram on Autonomic Function in Posttraumatic Stress Disorder Among Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF). AB - OBJECTIVE: Posttraumatic stress disorder is a chronic, debilitating condition that has become a growing concern among combat veterans. Previous research suggests that posttraumatic stress disorder disrupts normal autonomic responding and may increase the risk of cardiovascular disease and mortality. Measures of heart rate variability and QT interval variability have been used extensively to characterize sympathetic and parasympathetic influences on heart rate in a variety of psychiatric populations. The objective of this study was to better understand the effects of pharmacological treatment on autonomic reactivity in posttraumatic stress disorder. DESIGN: A 12-week, Phase IV, prospective, open label trial of escitalopram in veterans with combat-related posttraumatic stress disorder and comorbid depression. SETTING: An outpatient mental health clinic at a Veterans Affairs Medical Center. PARTICIPANTS: Eleven male veterans of Operations Enduring Freedom and Iraqi Freedom diagnosed with posttraumatic stress disorder and comorbid depression. MEASUREMENTS: Autonomic reactivity was measured by examining heart rate variability and QT interval variability. Treatment safety and efficacy were also evaluated pre- and post-treatment. RESULTS: We observed a reduction in posttraumatic stress disorder and depression symptoms from pre- to post-treatment, and escitalopram was generally well tolerated in our sample. In addition, we observed a decrease in high frequency heart rate variability and an increase in QT variability, indicating a reduction in cardiac vagal function and heightened sympathetic activation. CONCLUSION: These findings suggest that escitalopram treatment in patients with posttraumatic stress disorder and depression can trigger changes in autonomic reactivity that may adversely impact cardiovascular health. PMID- 26155374 TI - Recurrence of Lobar Hemorrhage: A Red Flag for Cerebral Amyloid Angiopathy related Inflammation? AB - Background. Recurrent lobar intracerebral hemorrhage is more commonly associated with cerebral amyloid angiopathy and less likely associated with hypertension. Cerebral amyloid angiopathy-related inflammation is a subgroup of cerebral amyloid angiopathy that can present with lobar intracerebral hemorrhage, encephalopathy, and seizures; wherein corticosteroids may facilitate favorable outcome. Whether recurrence of lobar intracerebral hemorrhage in cerebral amyloid angiopathy is related to cerebral amyloid angiopathy-related inflammation is unknown. Case presentation. A 68-year-old woman presented with an acute onset of confusion. She was known to have a history of recurrent lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. Brain imaging revealed previous sequelae of cerebral amyloid angiopathy and a new lobar intracerebral hemorrhage. An empirical diagnosis of cerebral amyloid angiopathy-related inflammation was made given the patent's clinical course of recurrence. Utilizing current evidence of criteria used to diagnose cerebral amyloid angiopathy-related inflammation, corticosteroid therapy was initiated with significant improvement in clinical and imaging characteristics. Discussion. Inflammatory pathways incited as a result of cerebrovascular amyloid deposition play a vital role in pathogenesis of cerebral amyloid angiopathy-related inflammation. We highlight the need to consider corticosteroid therapy in patients presenting with recurrent lobar intracerebral hemorrhage in the setting of cerebral amyloid angiopathy since inflammation may play a role in its pathophysiology. Evidence in the literature is sparse to suggest that cerebral amyloid angiopathy-related inflammation might be the root cause for the lobar intracerebral hemorrhage recurrence in cerebral amyloid angiopathy. Further studies are needed to identify mechanisms of recurrent hemorrhage, its correlations with cerebral amyloid angiopathy-related inflammation, and the potential role of corticosteroid therapy. PMID- 26155375 TI - Conversion Disorder- Mind versus Body: A Review. AB - In this article, the authors accentuate the signs and symptoms of conversion disorder and the significance of clinical judgment and expertise in order to reach the right diagnosis. The authors review the literature and provide information on the etiology, prevalence, diagnostic criteria, and the treatment methods currently employed in the management of conversion disorder. Of note, the advancements of neuropsychology and brain imaging have led to emergence of a relatively sophisticated picture of the neuroscientific psychopathology of complex mental illnesses, including conversion disorder. The available evidence suggests new methods with which to test hypotheses about the neural circuits underlying conversion symptoms. In context of this, the authors also explore the neurobiological understanding of conversion disorder. PMID- 26155376 TI - IRRITABLE BOWEL SYNDROME: Relationships with Abuse in Childhood. AB - Irritable bowel syndrome is allegedly the most common gastrointestinal diagnosis in the United States. The etiology of this syndrome appears to entail the interaction of both genes and the environment. One potential environmental contributory factor to irritable bowel syndrome is abuse in childhood. Of the various forms of abuses previously examined, sexual abuse in childhood appears to be the most patent contributor. However, both emotional and physical abuses may also contribute to irritable bowel syndrome, although less distinctly. Studies examining a combined childhood-abuse variable (i.e., sexual, emotional, and/or physical abuses) in relationship to irritable bowel syndrome also indicate inconsistent results. Given the presence of childhood abuse as a potential factor in the development of irritable bowel syndrome, a number of pathophysiological events are postulated to explain this relationship, including alterations in norepinephrine and serotonin levels as well as dysregulation of the hypothalamic pituitary-adrenal axis. Only future research will clarify the specific abuse elements (i.e., further clarification of the individual types of abuse, duration of abuse, roles of the perpetrator/victim) and the pathophysiological changes that culminate in irritable bowel syndrome. PMID- 26155377 TI - FORCED NORMALIZATION: Epilepsy and Psychosis Interaction. AB - Forced normalization is the emergence of psychoses following the establishment of seizure control in an uncontrolled epilepsy patient. Two illustrative clinical vignettes are provided about people with epilepsy that was newly controlled and followed by emergence of a psychosis; symptoms appeared only after attaining ictal control. For recognition and differential diagnosis purposes, understanding forced normalization is important in clinical practice. PMID- 26155378 TI - Antibiofilm Properties of Acetic Acid. AB - Bacterial biofilms are known to be extremely tolerant toward antibiotics and other antimicrobial agents. These biofilms cause the persistence of chronic infections. Since antibiotics rarely resolve these infections, the only effective treatment of chronic infections is surgical removal of the infected implant, tissue, or organ and thereby the biofilm. Acetic acid is known for its antimicrobial effect on bacteria in general, but has never been thoroughly tested for its efficacy against bacterial biofilms. In this article, we describe complete eradication of both Gram-positive and Gram-negative biofilms using acetic acid both as a liquid and as a dry salt. In addition, we present our clinical experience of acetic acid treatment of chronic wounds. In conclusion, we here present the first comprehensive in vitro and in vivo testing of acetic acid against bacterial biofilms. PMID- 26155379 TI - Biofilms and Wounds: An Overview of the Evidence. AB - Significance: Microorganisms can exist both in the planktonic and biofilm state. Each phenotypic state has a role to play in delaying healing and causing infections of both acute and chronic wounds. However, the virulent biofilm state is the fundamental reason that chronic wounds do not heal in a timely manner. We hypothesize that because microorganisms attach to any surface, biofilms can be found in all chronic wounds. However, it is not the biofilm per se that represents the greatest obstacle to the healing of a chronic wound, but its virulence and pathogenicity. Recent Advances: Numerous studies with animals and humans have identified biofilms in wounds. In particular, these studies have highlighted how biofilms impede host fibroblast development, inflammatory responses, and the efficacy of antimicrobial therapy. Despite this, the role biofilms play in affecting the healing of wounds is still vigorously debated. Critical Issues: Clinicians must understand the role that pathogenic biofilms play in impairing the healing of chronic wounds and in increasing the risk for wound infection, with its potentially catastrophic outcomes. The composition of the biofilm, its physiochemical properties, the climaxed indigenous microbiota and their virulence/pathogenicity, microbial numbers and the host's pathophysiology, and immunological fitness will govern the sustainability of a pathogenic biofilm in a wound and its resistance to interventions. Future Directions: Establishing which specific pathogenic biofilms delay wound healing should help guide better wound care practices. PMID- 26155380 TI - Chronic Wound Biofilm Model. AB - Significance: Multispecies microbial biofilms may contribute to wound chronicity by derailing the inherent reparative process of the host tissue. In the biofilm form, bacteria are encased within an extracellular polymeric substance and become recalcitrant to antimicrobials and host defenses. For biofilms of relevance to human health, there are two primary contributing factors: the microbial species involved and host response which, in turn, shapes microbial processes over time. This progressive interaction between microbial species and the host is an iterative process that helps evolve an acute-phase infection to a pathogenic chronic biofilm. Thus, long-term wound infection studies are needed to understand the longitudinal cascade of events that culminate into a pathogenic wound biofilm. Recent Advances: Our laboratory has recently published the first long term (2 month) study of polymicrobial wound biofilm infection in a translationally valuable porcine wound model. Critical Issues: It is widely recognized that the porcine system represents the most translationally valuable approach to experimentally model human skin wounds. A meaningful experimental biofilm model must be in vivo, include mixed species of clinically relevant microbes, and be studied longitudinally long term. Cross-validation of such experimental findings with findings from biofilm-infected patient wounds is critically important. Future Directions: Additional value may be added to the experimental system described above by studying pigs with underlying health complications (e.g., metabolic syndrome), as is typically seen in patient populations. PMID- 26155381 TI - Biofilms and Wounds: An Identification Algorithm and Potential Treatment Options. AB - Significance: The presence of a "pathogenic" or "highly virulent" biofilm is a fundamental risk factor that prevents a chronic wound from healing and increases the risk of the wound becoming clinically infected. There is presently no unequivocal gold standard method available for clinicians to confirm the presence of biofilms in a wound. Thus, to help support clinician practice, we devised an algorithm intended to demonstrate evidence of the presence of a biofilm in a wound to assist with wound management. Recent Advances: A variety of histological and microscopic methods applied to tissue biopsies are currently the most informative techniques available for demonstrating the presence of generic (not classified as pathogenic or commensal) biofilms and the effect they are having in promoting inflammation and downregulating cellular functions. Critical Issues: Even as we rely on microscopic techniques to visualize biofilms, they are entities which are patchy and dispersed rather than confluent, particularly on biotic surfaces. Consequently, detection of biofilms by microscopic techniques alone can lead to frequent false-negative results. Furthermore, visual identification using the naked eye of a pathogenic biofilm on a macroscopic level on the wound will not be possible, unlike with biofilms on abiotic surfaces. Future Direction: Lacking specific biomarkers to demonstrate microscopic, nonconfluent, virulent biofilms in wounds, the present focus on biofilm research should be placed on changing clinical practice. This is best done by utilizing an anti-biofilm toolbox approach, rather than speculating on unscientific approaches to identifying biofilms, with or without staining, in wounds with the naked eye. The approach to controlling biofilm should include initial wound cleansing, periodic debridement, followed by the application of appropriate antimicrobial wound dressings. This approach appears to be effective in removing pathogenic biofilms. PMID- 26155382 TI - Clinical and Antibiofilm Efficacy of Antimicrobial Hydrogels. AB - Significance: Hydrogels have been shown to have a significant role to play in wound healing. Hydrogels are used to assist in the management of dry, sloughy, or necrotic wounds. However, recent scientific evidence has shown that biofilms delay wound healing and increase a wound propensity to infection. It is therefore essential that hydrogels incorporating antimicrobials demonstrate efficacy on biofilms. Consequently, it is the aim of this article to review the efficacy of hydrogels, incorporating antimicrobials, on wounds with specific reference to their efficacy on biofilms. Recent Advances: Technologies being developed for the management of wounds are rapidly expanding. In particularly next-generation hydrogels, incorporating copolymers, have been reported to enable the smart release of antimicrobials. This has led to the development of a more tailored patient-specific antimicrobial hydrogel therapy. Critical Issues: Evidence relating to the efficacy of hydrogels, incorporating antimicrobials, on biofilms within both the in vitro and in vivo environments is lacking. Future Direction: Studies that investigate the efficacy of antimicrobial hydrogel wound dressings on both in vivo and in vitro biofilms are important. However, there is a significant need for better and more reproducible in vivo biofilm models. Until this is possible, data generated from appropriate and representative in vitro models will help to assist researchers and clinicians in evaluating antimicrobial and antibiofilm hydrogel technology for the extrapolation of efficacy data relevant to biofilms present in the in vivo environment. PMID- 26155383 TI - Silver and Alginates: Role in Wound Healing and Biofilm Control. AB - Significance: Chronic wounds are known to be a significant issue globally. Of concern in wounds are the numbers and types of residing microorganisms and the ability of the host's immune system to control their proliferation. Wound healing is impeded by colonizing microorganisms growing within the biofilm phenotypic state. In this state microorganisms are recalcitrant to routinely impeded by used antimicrobial interventions. Recent advances: Silver has been reported to demonstrate efficacy on planktonic microorganisms both within the in vitro and in vivo environments. However, when silver is incorporated into a wound dressing, its antimicrobial efficacy on biofilms within the in vivo environment remains contentious. Critical Issues: Unequivocal evidence of the efficacy of silver, and wound dressings containing silver, on biofilms in clinical situations is lacking. This is principally due to the deficiency of definite biofilm definitions, markers, and evidence in the chronic wound environment. Future Direction: Research studies demonstrating antimicrobial efficacy on in vitro biofilms can be used to generate data and information appropriate for extrapolation and applicability to the in vivo environment. It is very important that inventors of antimicrobial wound dressings ensure efficacy against both planktonic and sessile microorganisms, within the in vitro and in vivo environments. PMID- 26155384 TI - EDTA: An Antimicrobial and Antibiofilm Agent for Use in Wound Care. AB - Significance: Methods employed for preventing and eliminating biofilms are limited in their efficacy on mature biofilms. Despite this a number of antibiofilm formulations and technologies incorporating ethylenediaminetetraacetic acid (EDTA) have demonstrated efficacy on in vitro biofilms. The aim of this article is to critically review EDTA, in particular tetrasodium EDTA (tEDTA), as a potential antimicrobial and antibiofilm agent, in its own right, for use in skin and wound care. EDTA's synergism with other antimicrobials and surfactants will also be discussed. Recent Advances: The use of EDTA as a potentiating and sensitizing agent is not a new concept. However, currently the application of EDTA, specifically tEDTA as a stand-alone antimicrobial and antibiofilm agent, and its synergistic combination with other antimicrobials to make a "multi-pronged" approach to biofilm control is being explored. Critical Issues: As pathogenic biofilms in the wound increase infection risk, tEDTA could be considered as a potential "stand-alone" antimicrobial/antibiofilm agent or in combination with other antimicrobials, for use in both the prevention and treatment of biofilms found within abiotic (the wound dressing) and biotic (wound bed) environments. The ability of EDTA to chelate and potentiate the cell walls of bacteria and destabilize biofilms by sequestering calcium, magnesium, zinc, and iron makes it a suitable agent for use in the management of biofilms. Future Direction: tEDTA's excellent inherent antimicrobial and antibiofilm activity and proven synergistic and permeating ability results in a very beneficial agent, which could be used for the development of future antibiofilm technologies. PMID- 26155385 TI - The Use of Silicone Adhesives for Scar Reduction. AB - Significance: This article discusses the history and developments of silicone gel sheeting (SGS) scar therapy. Furthermore, we review a breadth of literature to gain an insight into how and why topical silicone gels remain the favored treatment of medical experts in scar management. We also analyze an ever increasing number of alternative therapies claiming to provide enhanced scar reduction performance. Recent Advances: Topical silicone gel treatments seem to remain the first point of clinical recommendation in scar management. SGS has been used in scar therapy for over 30 years, during which its efficacy has been the subject of numerous clinical evaluations. Critical Issues: While the exact mechanisms by which SGS improves hypertrophic scars, keloid development and recovery are yet to be fully agreed upon, its ability to do so remains largely undisputed at present. However, there still is ongoing deliberation over the exact mechanism of action of silicone in improving a scar. At present it is likely that through occlusion of the scar site and hydration of the wound bed, the overactivity of scar-related cells is suppressed, and their activity normalized. Future Direction: The clinical support of topical silicone gel products, relative to all alternative scar therapies, is considered the internationally recommended first-line form of scar management, and favored by consensus among healthcare professionals. However, there still remains the need for further clinical evidence and a better understanding of the mechanism behind the benefit of silicone gel for use in the prevention of abnormal scarring. PMID- 26155386 TI - The Effect of pH on the Extracellular Matrix and Biofilms. AB - Significance: Chronic wounds become caught in a state of inflammation causing an increase in levels of degrading proteases, which destroy components of the extracellular matrix (ECM) that are essential for the wound healing process. This review aims to highlight and provide readers with an overview of what is currently known about the role of pH and its effect on the ECM and biofilms within healing and nonhealing wounds. Recent Advances: The pH profiles of healthy skin, acute wounds, and chronic wounds differ significantly. Chronic wounds have an alkaline pH whereas healthy skin has a slightly acidic pH. Although there is evidence on the effect of pH on protease production and bacterial proliferation in wounds, there is little evidence to show its effect on ECM synthesis and degradation. Critical Issues: The implications for the complex nature of chronic wounds are that no single treatment is relevant for all wounds, but rather a combination of methodologies must be adopted. It is known that pH of a wound reduces throughout the stages of healing, suggesting that wound pH measurements could be beneficial to identify nonhealing wounds earlier and decide on the most appropriate course of treatment. Future Direction: Wound healing is a very complex process with multiple factors known to play a role. All aspects of the nonhealing wound (defective ECM, pH, microbial invasion, and excess proteases) need to be taken into account when investigating or clinically treating a chronic wound. PMID- 26155387 TI - Extending the lifespan and efficacies of immune cells used in adoptive transfer for cancer immunotherapies-A review. AB - Cells used in adoptive cell-transfer immunotherapies against cancer include dendritic cells (DCs), natural-killer cells, and CD8+ T-cells. These cells may have limited efficacy due to their lifespan, activity, and immunosuppressive effects of tumor cells. Therefore, increasing longevity and activity of these cells may boost their efficacy. Four cytokines that can extend immune effector cell longevity are IL-2, IL-7, IL-21, and IL-15. This review will discuss current knowledge on effector-cell lifespans and the mechanisms by which IL-2, IL-7, IL 15, and IL-21 can extend effector-cell longevity. We will also discuss how lifespan and efficacy of these cells can be regulated to allow optimal clinical benefits. PMID- 26155388 TI - Trial Watch: Therapeutic vaccines in metastatic renal cell carcinoma. AB - Despite the renaissance of cancer immunotherapy, no novel immunotherapy has been approved for the treatment of renal cell cancer (RCC) since the availability of recombinant cytokines (interleukin-2, interferon-alpha). All vaccine trials have failed to meet their endpoints although they have highlighted potential predictive biomarkers (e.g., pre-existing immune response, hematological parameters, tumor burden). Recent advances in immunomodulatory therapies have prompted the study of combination treatments targeting the tumor immunosuppressive microenvironment consisting of regulatory T-cells (Treg), myeloid suppressor cells, and cytokines. Approaches under investigation are use of inhibitors to curb the overexpression of immune checkpoint ligands by tumor cells (e.g., anti-CTLA-4, anti-PD-1/PD-L1) and exploiting the immunomodulatory effects of anti-angiogenic agents that are the current standard of metastatic RCC care. Phase III trials are focusing on the possible synergy between therapeutic vaccines (e.g., IMA-901 and AGS-003) and anti-angiogenic agents. PMID- 26155389 TI - Rapid generation of NY-ESO-1-specific CD4+ THELPER1 cells for adoptive T-cell therapy. AB - Tumor-associated antigens such as NY-ESO-1 are expressed in a variety of solid tumors but absent in mature healthy tissues with the exception of germline cells. The immune system anti-cancer attack is mediated by cell lysis or induction of growth arrest through paralysis of tumor cells, the latter of which can be achieved by tumor-specific CD4+, IFNgamma-producing THelper type 1 (TH1) cells. Translation of these immune-mediated mechanisms into clinical application has been limited by availability of immune effectors, as well as the need for complex in vitro protocols and regulatory hurdles. Here, we report a procedure to generate cancer-testis antigen NY-ESO-1-targeting CD4+ TH1 cells in vitro for cancer immunotherapy in the clinic. After in vitro sensitization by stimulating T cells with protein-spanning, overlapping peptide pools of NY-ESO-1 in combination with IL-7 and low dose IL-2, antigen-specific T cells were isolated using IFNgamma capture technique and subsequently expanded with IL-2, IL-7 and IL-15. Large numbers of NY-ESO-1-specific CD4+ T cells with a TH1 cytokine profile and lower numbers of cytokine-secreting CD8+ T cells could be generated from healthy donors with a high specificity and expansion potential. Manufactured CD4+ T cells showed strong specific TH1-responses with IFNgamma+, TNFalpha+, IL-2+ and induced cell cycle arrest and apoptosis in tumor cells. The protocol is GMP-grade and approved by the regulatory authorities. The tumor-antigen specific CD4+ TH1 lymphocytes can be adoptively transferred as a T-cell therapy to boost anticancer immunity and this novel cancer treatment approach is applicable to both T cells from healthy allogeneic donors as well as to autologous T cells derived from cancer patients. PMID- 26155390 TI - Highly clonal regulatory T-cell population in follicular lymphoma - inverse correlation with the diversity of CD8+ T cells. AB - The immune microenvironment in follicular lymphoma (FL) plays an important role in controlling disease characteristics. To characterize the T-cell receptor (TCR) repertoire in follicular lymphoma (FL) tissues, we applied a next-generation sequencing platform and deeply sequenced TCR cDNAs of T-cell subset populations present in pretreatment FL biopsy specimens. T regulatory cell (Treg) TCRs in FL tissues revealed a highly oligoclonal expansion compared to those in control lymph nodes. Furthermore, an inverse correlation was observed between the diversity of Treg and CD8+ TCRs in FL specimens. Interestingly, a tumor from an FL patient, who had not received anticancer treatment for more than 10 years, was found to have missense mutations in the peptide-binding domain of both human leukocyte antigen (HLA) class I and II molecules, which might have presented tumor-specific antigens and enhanced host immune responses. Although further verification is required, our data suggest that the T-cell repertoire is skewed and restricted in FL and support the evolving understanding of the microenvironment in this disease. PMID- 26155392 TI - The mutually regulatory loop of epithelial-mesenchymal transition and immunosuppression in cancer progression. AB - Epithelial-mesenchymal transition and immunosuppression are crucial for cancer metastasis and treatment resistance. The mechanism by which these distinct processes are co-opted remains incompletely understood. Our recent work has exposed the "dirty affairs" of the 2 at the tumor site, thus calling for a combined therapy to break such a dangerous liaison. PMID- 26155391 TI - PDL1 expression is an independent prognostic factor in localized GIST. AB - Gastrointestinal stromal tumors (GIST) are the most frequently occurring digestive sarcomas. The prognosis of localized GIST is heterogeneous, notably for patients with an Armed Forces Institute of Pathology (AFIP) intermediate or high risk of relapse. Despite imatinib effectiveness, it is crucial to develop therapies able to overcome the resistance mechanisms. The immune system represents an attractive prognostic and therapeutic target. The Programmed cell Death 1 (PD1)/programmed cell death ligand 1 (PDL1) pathway is a key inhibitor of the immune response; recently, anti-PD1 and anti-PDL1 drugs showed very promising results in patients with solid tumors. However, PDL1 expression has never been studied in GIST. Our objective was to analyze PDL1 expression in a large series of clinical samples. We analyzed mRNA expression data of 139 operated imatinib untreated localized GIST profiled using DNA microarrays and searched for correlations with histoclinical features including postoperative metastatic relapse. PDL1 expression was heterogeneous across tumors and was higher in AFIP low-risk than in high-risk samples, and in samples without than with metastatic relapse. PDL1 expression was associated with immunity-related parameters such as T-cell-specific and CD8+ T-cell-specific gene expression signatures and probabilities of activation of interferon alpha (IFNalpha), IFNgamma, and tumor necrosis factor alpha (TNFalpha) pathways, suggesting positive correlation with a cytotoxic T-cell response. In multivariate analysis, the PDL1-low group was associated with a higher metastatic risk independently of the AFIP classification and the KIT mutational status. In conclusion, PDL1 expression refines the prediction of metastatic relapse in localized GIST and might improve our ability to better tailor adjuvant imatinib. In the metastatic setting, PDL1 expression might guide the use of PDL1 inhibitors, alone or associated with tyrosine kinase inhibitors. PMID- 26155393 TI - Chronic inflammation in endometriosis and endometriosis-associated ovarian cancer: New roles for the "old" complement pathway. AB - Immune escape is consequential for cancer development. Identifying abnormalities of the immune microenvironment during early carcinogenesis can provide insight into disease pathogenesis and unravel new preventive or therapeutic targets. We recently conducted a comprehensive immune gene expression analysis in endometriosis and endometriosis-associated ovarian cancer and explored new mechanistic roles for the complement pathway. PMID- 26155394 TI - TCR-dependent sensitization of human gammadelta T cells to non-myeloid IL-18 in cytomegalovirus and tumor stress surveillance. AB - Human gammadelta T cells contribute to tissue homeostasis under normal conditions and participate in lymphoid stress surveillance against infection and tumors. However, the molecular mechanisms underlying the recognition of complex cell stress signatures by gammadelta T cells are still unclear. Tumor cells and human cytomegalovirus (HCMV)-infected cells are known targets of gammadelta T cells. We show here that many tumor and CMV-infected cells express caspase-1 inflammasomes and release interleukin (IL)-18. Engagement of the T-cell receptor (TCR) on Vdelta2neg gammadelta T cells controlled the direct innate immune sensing of IL 18 that enhanced cytotoxicity and interferon gamma (IFNgamma) production. This TCR-dependent sensitization to IL-18 was mediated by the upregulation of the innate IL-18 receptor beta chain (IL-18Rbeta) expression. These findings shed light on inflammasomes as a unified stress signal of tumor and infected cells to alert gammadelta T cells. Moreover, uncovering the TCR-mediated sensitization of gammadelta T cells to inflammatory mediators establishes a molecular link between the innate and adaptive immune functions of gammadelta T cells that could fine tune the commitment of antigen-experienced gammadelta T cells to inflammatory responses. PMID- 26155395 TI - Expression profile of the human IDO1 protein, a cancer drug target involved in tumoral immune resistance. AB - Tryptophan catabolism by indoleamine 2,3-dioxygenase (IDO1) is a physiological immunoregulatory mechanism often hijacked by tumors. Our recent extensive study of IDO1 protein expression in human tissues showed expression in mature dendritic cells and in pulmonary and placental endothelial cells. IDO1 was also expressed in 56% of tumors, either by tumoral, stromal, or endothelial cells. These results and reagent will guide the clinical development of IDO1 inhibitors for cancer therapy. PMID- 26155396 TI - Shaping the tumor microenvironment with Modified Vaccinia Virus Ankara and TLR9 ligand. AB - Our preclinical data demonstrate that an intravenous injection of Modified Vaccinia virus Ankara induces CD8+ lymphocytes to infiltrate organs to control the growth of orthotopic renal carcinoma upon combination with a toll-like receptor 9 agonist. Such shaping of the tumor microenvironment could constitute the basis of more effective clinical protocols of tumor immunotherapy. PMID- 26155397 TI - CD39: A complementary target to immune checkpoints to counteract tumor-mediated immunosuppression. AB - We report that CD39-expressing-melanoma cells inhibited both T-cell proliferation and the generation of cytotoxic effectors in an adenosine-dependent manner, and that treatment with a CD39-blocking antibody alleviated tumor-mediated immunosuppression. Thus, blocking CD39 ectonucleotidase may represent a novel immunotherapeutic strategy to restore antitumor immunity. PMID- 26155398 TI - Time to Akt: Superior tumor-reactive T cells for adoptive immunotherapy. AB - T cells are crucial players in the protection against cancer, and can be used in adoptive cell therapy to prevent or treat relapse. However, their state of differentiation determines their effectiveness, with early memory cells being the most favorable. Here, we discuss restraining of differentiation to engineer the ultimate tumor-reactive T cell. PMID- 26155399 TI - Akt1 and -2 inhibition diminishes terminal differentiation and enhances central memory CD8+ T-cell proliferation and survival. AB - The CD8 + T-cell response comprises terminally differentiated effector cells and antigen-experienced memory T cells. The latter encompass central (TCM) and effector (TEM) memory cells. TCM cells are superior in their protection against viral and bacterial challenges and mediation of antitumor immunity due to their higher proliferative ability upon antigen re-encounter. Defining a mechanism to enhance TCM cells and delay terminal differentiation of CD8 + T cells is crucial for cancer immune therapy, as it can promote a better tumor immune response. The differentiation of CD8 + memory T cells is thought to be coordinated by the phosphoinositide 3-kinase (PI3K)/Akt pathway. We, therefore, investigated the role of Akt isoforms in the differentiation and proliferation of memory CD8 + T cells. We found that Akt1 and Akt2, but not Akt3, drive the terminal differentiation of CD8 + T cells, and their inhibition enhances the therapeutically superior TCM phenotype. Furthermore, the inhibition of Akt1 and Akt2, but not Akt 3, delays CD8 + T-cell exhaustion and preserves naive and TCM CD8 + T cells, thus enhancing their proliferative ability and survival and prolonging their cytokine and Granzyme B production ability. Here, we define a mechanism in which proliferative potential, function, and survival of CD8 + T cells are enhanced by maintaining a reservoir of TCM and naive cells using only Akt1 and Akt2 inhibition. Therefore, our findings strongly suggest the utility of using Akt1 and Akt2 inhibitors to modulate CD8 + T cells, both for adoptive cell transfer and vaccine-based cancer immune therapies. PMID- 26155400 TI - Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival. AB - There is increased production of plasmacytoid dendritic cells (pDCs) in the bone marrow (BM) of multiple myeloma (MM) patients and these favor Th22 cell differentiation. Here, we found that the frequency of interleukin (IL)-22+IL-17 IL-13+ T cells is significantly increased in peripheral blood (PB) and BM of stage III and relapsed/refractory MM patients compared with healthy donors and patients with asymptomatic or stage I/II disease. Th22 cells cloned from the BM of MM patients were CCR6+CXCR4+CCR4+CCR10- and produced IL-22 and IL-13 but not IL-17. Furthermore, polyfunctional Th22-Th2 and Th22-Th1 clones were identified based on the co-expression of additional chemokine receptors and cytokines (CRTh2 or CXCR3 and IL-5 or interferon gamma [IFNgamma], respectively). A fraction of MM cell lines and primary tumors aberrantly expressed the IL-22RA1 and IL-22 induced STAT-3 phosphorylation, cell growth, and resistance to drug-induced cell death in MM cells. IL-13 treatment of normal BM mesenchymal stromal cells (MSCs) induced STAT-6 phosphorylation, adhesion molecule upregulation, and increased IL-6 production and significantly favored MM cell growth compared with untreated BM MSCs. Collectively, our data show that increased frequency of IL-22+IL-17-IL-13+ T cells correlates with poor prognosis in MM through IL-22 and IL-13 protumor activity and suggest that interference with IL-22 and IL-13 signaling pathways could be exploited for therapeutic intervention. PMID- 26155402 TI - Restoration of defective cross-presentation in tumors by gemcitabine. AB - Tumor antigen cross-presentation by dendritic cells (DCs) to specific CD8+ T cells is central to antitumor immunity. Although highly efficient in draining lymph nodes, it is defective within the tumor site itself. Importantly, an immunogenic chemotherapy, gemcitabine, reverses this defect, allowing the potential re-stimulation of cytotoxic T lymphocytes within tumor sites. PMID- 26155401 TI - Antitumor immunization of mothers delays tumor development in cancer-prone offspring. AB - Maternal immunization is successfully applied against some life-threatening infectious diseases as it can protect the mother and her offspring through the passive transfer of maternal antibodies. Here, we sought to evaluate whether the concept of maternal immunization could also be applied to cancer immune prevention. We have previously shown that antibodies induced by DNA vaccination against rat Her2 (neu) protect heterozygous neu-transgenic female (BALB-neuT) mice from autochthonous mammary tumor development. We, herein, seek to evaluate whether a similar maternal immunization can confer antitumor protection to BALB neuT offspring. Significantly extended tumor-free survival was observed in BALB neuT offspring born and fed by mothers vaccinated against neu, as compared to controls. Maternally derived anti-neu immunoglobulin G (IgG) was successfully transferred from mothers to newborns and was responsible for the protective effect. Vaccinated mothers and offspring also developed active immunity against neu as revealed by the presence of T-cell-mediated cytotoxicity against the neu immunodominant peptide. This active response was due to the milk transfer of immune complexes that were formed between the neu extracellular domain, shed from vaccine-transfected muscle cells, and the anti-neu IgG induced by the vaccine. These findings show that maternal immunization has the potential to hamper mammary cancer in genetically predestinated offspring and to develop into applications against lethal neonatal cancer diseases for which therapeutic options are currently unavailable. PMID- 26155403 TI - Intratumoral delivery of mRNA: Overcoming obstacles for effective immunotherapy. AB - The immunosuppressive tumor microenvironment (TME) is a major obstacle in cancer immunotherapy. Therefore, it has gained attention as a target site. mRNA emerged as a versatile drug class for cancer therapy. We reported that intratumoral administration of mRNA encoding the fusokine Fbeta2 supports tumor-specific T cell immunity. This study provides proof of concept of the use of mRNA to modulate the TME. PMID- 26155404 TI - HLA class I as a predictor of clinical prognosis and CTL infiltration as a predictor of chemosensitivity in ovarian cancer. AB - Cytotoxic T lymphocytes (CTLs) recognize the human leukocyte antigen (HLA) class I and antigenic peptide complex, and they play a crucial role in cancer immunity. Our recent study revealed that HLA class I downregulation is related to poorer prognosis and a low level of intratumoral CTLs is associated with platinum resistance, indicating the significance of immunological surveillance. PMID- 26155405 TI - B cells drive Th2 responses by instructing human dendritic cell maturation. AB - Dendritic cells (DCs) are known to regulate the functions of various immune cells. Reciprocal signaling by these immune cells also "educate" the DCs and determine the quality of the ensuing immune responses. Recently, we demonstrated that human DCs undergo maturation upon interaction with activated B cells to acquire unique abilities to promote polarization of Th2 cells. PMID- 26155406 TI - Deciphering the genetic evolution of T-cell resistance in melanoma. AB - T-cell-based immunotherapy of melanoma becomes ineffective when beta2m-deficient tumor cells of a human leukocyte antigen (HLA) class I-negative phenotype grow out. We demonstrated that an early-acquired chromosomal deletion and subsequent inactivating gene mutation lead to beta2m deficiency, suggesting that melanoma cells can genetically evolve to avoid being recognized by CD8+ T cells. PMID- 26155407 TI - Personalized peptide vaccination for advanced colorectal cancer. AB - We have developed a novel approach in cancer immunotherapy, the personalized peptide vaccination (PPV), in which human leukocyte antigen (HLA)-matched peptides are selected on the basis of preexisting host immunity before vaccination. Recently, we demonstrated the feasibility of PPV in previously treated patients with advanced colorectal cancer, thus warranting further clinical development of this approach. PMID- 26155409 TI - New role for antigen-presenting activated pDCs in promoting Th17 cells and impacting antitumor immunity. AB - Plasmacytoid dendritic cells (pDCs) are not only potent inflammatory cytokine producers but also function as antigen-presenting cells (APCs). We have shown that vaccination using CpG-B activated tumor antigen (Ag) presenting pDCs induce Th17 cells that promote intratumoral immune cell recruitment, including antitumor cytotoxic T lymphocytes CTLs. Therefore, strategies targeting both innate and adaptive pDC functions may improve antitumor T-cell immunity. PMID- 26155410 TI - Tumor infiltrating CD8+ T lymphocyte count is independent of tumor TLR9 status in treatment naive triple negative breast cancer and renal cell carcinoma. AB - Toll-like receptor 9 (TLR9) is a cellular DNA-receptor of the innate immune system that is widely expressed in cancers. We demonstrated that low tumor TLR9 expression predicts poor disease-specific survival in triple negative breast cancer (TNBC) and renal cell carcinoma (RCC). We hypothesized that this is because TLR9 expression affects tumor immunophenotype. To begin to test this, we compared the number of tumor infiltrating CD8+ T lymphocytes with TLR9 expression in treatment naive breast cancer (n = 197) and RCC (n = 94) cohorts with known TLR9 expression status. CD8+ T lymphocyte counts were assayed with image analysis after immunohistochemistry (IHC). Tumor TLR9 expression was not correlated with CD8+ T cell counts in breast cancer or RCC. CD8+ T cell counts were significantly associated with tumor proliferation index in TNBC, but not in non-TNBC. CD8+ T cell counts were also significantly associated with tumor grade in non-TNBC, but not in TNBC. In RCC, CD8+ T cell counts were significantly associated with tumor stage. CD8+ T cell counts were significantly associated with prognosis in TNBC and RCC, but the presence of CD8+ T cells in these tumors had opposite effects on disease-specific survival: High CD8+ counts were associated with better prognosis in TNBC and worse prognosis in RCC. Among TNBC patients, those with low tumor TLR9 and low CD8+ T cell counts had the poorest prognosis (log-rank p = 0.0002 vs. high tumor TLR9 and high CD8+ T cell count). In conclusion, pre-treatment tumor TLR9 status is not associated with tumor infiltrating CD8+ T lymphocytes in TNBC or RCC. The combination of TLR9 and CD8+ TIL count might be a novel composite prognostic marker in TNBC. PMID- 26155408 TI - Trial watch: Naked and vectored DNA-based anticancer vaccines. AB - One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm. PMID- 26155411 TI - gammadelta T cells and epigenetic drugs: A useful merger in cancer immunotherapy? AB - gammadelta T cell-based immunotherapeutic strategies in cancer patients are as yet of limited success. Drugs targeting epigenetic mechanisms including histone acetylation and DNA methylation trigger cell death in tumor cells but in addition have immunomodulatory activity. Here, we discuss the potential benefit of combining both strategies in cancer immunotherapy. PMID- 26155412 TI - Cervical (pre)neoplastic microenvironment promotes the emergence of tolerogenic dendritic cells via RANKL secretion. AB - The progression of genital human papillomavirus (HPV) infections into preneoplastic lesions suggests that infected/malignant cells are not adequately recognized by the immune system. In this study, we demonstrated that cervical/vulvar cancer cells secrete factor(s) that affect both the maturation and function of dendritic cells (DC) leading to a tolerogenic profile. Indeed, DC cocultured with cancer cell lines display both a partially mature phenotype after lipopolysaccharide (LPS) maturation and an altered secretory profile (IL-10high and IL-12p70low). In addition, tumor-converted DC acquire the ability to alter T cell proliferation and to induce FoxP3+ suppressive T cells from naive CD4+ T cells. Among the immunosuppressive factors implicated in DC alterations in genital (pre)neoplastic microenvironment, we identified receptor activator of nuclear factor kappa-B ligand (RANKL), a TNF family member, as a potential candidate. For the first time, we showed that RANKL expression strongly increases during cervical progression. We also confirmed that RANKL is directly secreted by cancer cells and this expression is not related to HPV viral oncoprotein induction. Interestingly, the addition of osteoprotegerin (OPG) in coculture experiments reduces significantly the inhibition of DC maturation, the release of a tolerogenic cytokine profile (IL-12low IL-10high) and the induction of regulatory T (Treg) cells. Our findings suggest that the use of inhibitory molecules directed against RANKL in cervical/vulvar (pre)neoplastic lesions might prevent alterations of DC functionality and represent an attractive strategy to overcome immune tolerance in such cancers. PMID- 26155413 TI - Are BiTEs the "missing link" in cancer therapy? AB - Conventional treatment for cancer routinely includes surgical resection and some combination of chemotherapy and radiation. These approaches are frequently accompanied by unintended and highly toxic collateral damage to healthy tissues, which are offset by only marginal prognostic improvements in patients with advanced cancers. This unfortunate balance has driven the development of novel therapies that aim to target tumors both safely and efficiently. Over the past decade, mounting evidence has supported the therapeutic utility of T-cell centered cancer immunotherapy, which, in its various iterations, has been shown capable of eliciting highly precise and robust antitumor responses both in animal models and human trials. The identification of tumor-specific targets has further fueled a growing interest in T-cell therapies given their potential to circumvent the non-specific nature of traditional treatments. Of the several strategies geared toward achieving T-cell recognition of tumor, bispecific antibodies (bsAbs) represent a novel class of biologics that have garnered enthusiasm in recent years due to their versatility, specificity, safety, cost, and ease of production. Bispecific T-cell Engagers (BiTEs) are a subclass of bsAbs that are specific for CD3 on one arm and a tumor antigen on the second. As such, BiTEs function by recruiting and activating polyclonal populations of T-cells at tumor sites, and do so without the need for co-stimulation or conventional MHC recognition. Blinatumomab, a well-characterized BiTE, has emerged as a promising recombinant bscCD19*CD3 construct that has demonstrated remarkable antitumor activity in patients with B-cell malignancies. This clinical success has resulted in the rapid extension of BiTE technology against a greater repertoire of tumor antigens and the recent US Food and Drug Administration's (FDA) accelerated approval of blinatumomab for the treatment of a rare form of acute lymphoblastic leukemia (ALL). In this review, we dissect the role of T-cell therapeutics in the new era of cancer immunotherapy, appraise the value of CAR T-cells in the context of solid tumors, and discuss why the BiTE platform may rescue several of the apparent deficits and shortcomings of competing immunotherapies to support its widespread clinical application. PMID- 26155414 TI - Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell carcinoma is associated with poor prognosis. AB - Dendritic cells (DCs) essentially contribute to the induction and regulation of innate and adaptive immunity. Based on these important properties, DCs may profoundly influence tumor progression in patients. However, little is known about the role of distinct human DC subsets in primary tumors and their impact on clinical outcome. In the present study, we investigated the characteristics of human 6-sulfo LacNAc (slan) DCs in clear cell renal cell carcinoma (ccRCC). slanDCs have been shown to display various tumor-directed properties and to accumulate in tumor-draining lymph nodes from patients. When evaluating 263 ccRCC and 227 tumor-free tissue samples, we found increased frequencies of slanDCs in ccRCC tissues compared to tumor-free tissues. slanDCs were also detectable in the majority of 24 metastatic lymph nodes and 67 distant metastases from ccRCC patients. Remarkably, a higher density of slanDCs was significantly associated with a reduced progression-free, tumor-specific or overall survival of ccRCC patients. Tumor-infiltrating slanDCs displayed an immature phenotype expressing interleukin-10. ccRCC cells efficiently impaired slanDC-induced T-cell proliferation and programming as well as natural killer (NK) cell activation. In conclusion, these findings indicate that higher slanDC numbers in ccRCC tissues are associated with poor prognosis. The induction of a tolerogenic phenotype in slanDCs leading to an insufficient activation of innate and adaptive antitumor immunity may represent a novel immune escape mechanism of ccRCC. These observations may have implications for the design of therapeutic strategies that harness tumor-directed functional properties of DCs against ccRCC. PMID- 26155415 TI - Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival. AB - Exosomes in plasma of glioma patients hold promise as biomarkers of prognosis. We aimed to determine whether changes in total exosomal protein and mRNA expression levels could serve as surrogate markers of immunological and clinical responses in glioma patients receiving antitumor vaccines. Exosomes were isolated from pre/post-vaccine plasma specimens in 20/22 patients enrolled in a phase I/II trial with the antitumor vaccine. Exosomal protein content was analyzed and mRNA expression levels for 24 genes were simultaneously assessed by qRT-PCR. Pre- to post-vaccination changes in exosomal protein and DeltaCt values were correlated with immunological and clinical responses and survival using Spearman rank statistics and hazard ratios (HR). Exosomal protein levels positively correlated (p < 0.0043) with the WHO tumor grade at diagnosis. Protein levels were lower in post- vs. pre-vaccination exosome fractions. Post-therapy increases in tumor size were associated with elevations in exosome proteins in glioblastoma but not always in anaplastic astrocytoma (AA). Only exosomal DeltaCt values for IL-8, TIMP-1, TGF-beta and ZAP70 were significant (p < 0.04 to p < 0.001). The DeltaCt for IL-8 and TGF-beta mRNA positively correlated with post-vaccine immunologic responses to glioma antigens, while DeltaCt for TIMP-1 mRNA was negatively correlated to DeltaCt for IL-8 and TGF-beta. Only DeltaCt for IL-8 weakly correlated with OS and time to progression (TTP). In post-vaccine exosomes of the longest surviving patient with AA, mRNA for PD-1 was persistently elevated. Protein and mRNA expression levels for immune-related genes in plasma exosomes were useful in evaluating glioma patients' response to vaccination therapy. PMID- 26155416 TI - T cell receptor-therapy in HBV-related hepatocellularcarcinoma. AB - Adoptive transfer of lymphocytes expressing engineered T cell receptors (TCR) is a promising option for cancer treatment and could include hepatocellularcarcinoma (HCC), where therapeutic options are limited. We have recently investigated whether hepatitis B viral antigens can act as a HCC-specific antigen and thus be targeted by adoptively transferred HBV-specific TCR redirected T cells. PMID- 26155417 TI - Tumor-infiltrating plasmacytoid dendritic cells promote immunosuppression by Tr1 cells in human liver tumors. AB - CD4+ type 1 T regulatory (Tr1) cells have a crucial role in inducing tolerance. Immune regulation by these cells is mainly mediated through the secretion of high amounts of IL-10. Several studies have suggested that this regulatory population may be involved in tumor-mediated immune-suppression. However, direct evidence of a role for Tr1 cells in human solid tumors is lacking. Using ex vivo isolated cells from individuals with hepatocellular carcinoma (HCC; n = 39) or liver metastases from colorectal cancer (LM-CRC; n = 60) we identify a CD4+FoxP3-IL-13 IL-10+ T cell population in tumors of individuals with primary or secondary liver cancer that is characterized as Tr1 cells by the expression of CD49b and the lymphocyte activation gene 3 (LAG-3) and strong suppression activity of T cell responses in an IL-10 dependent manner. Importantly, the presence of tumor infiltrating Tr1 cells is correlated with tumor infiltration of plasmacytoid dendritic cells (pDCs). pDCs exposed to tumor-derived factors enhance IL-10 production by Tr1 cells through up-regulation of the inducible co-stimulatory ligand (ICOS-L). These findings suggest a role for pDCs and ICOS-L in promoting intra-tumoral immunosuppression by Tr1 cells in human liver cancer, which may foster tumor progression and which might interfere with attempts of immunotherapeutic intervention. PMID- 26155418 TI - Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment. AB - Extracellular vesicles (EVs) have been shown to transfer various molecules, including functional RNA between cells and this process has been suggested to be particularly relevant in tumor-host interactions. However, data on EV-mediated RNA transfer has been obtained primarily by in vitro experiments or involving ex vivo manipulations likely affecting its biology, leaving their physiological relevance unclear. We engineered glioma and carcinoma tumor cells to express Cre recombinase showing their release of EVs containing Cre mRNA in various EV subfractions including exosomes. Transplantation of these genetically modified tumor cells into mice with a Cre reporter background leads to frequent recombination events at the tumor site. In both tumor models the majority of recombined cells are CD45+ leukocytes, predominantly Gr1+CD11b+ myeloid-derived suppressor cells (MDSCs). In addition, multiple lineages of recombined cells can be observed in the glioma model. In the lung carcinoma model, recombined MDSCs display an enhanced immunosuppressive phenotype and an altered miRNA profile compared to their non-recombined counterparts. Cre-lox based tracing of tumor EV RNA transfer in vivo can therefore be used to identify individual target cells in the tumor microenvironment for further mechanistical or functional analysis. PMID- 26155420 TI - The crosstalk between acinar cells with Kras mutations and M1-polarized macrophages leads to initiation of pancreatic precancerous lesions. AB - Recent studies on the processes that lead to the development of pancreatic cancer indicate that inflammatory macrophages have key functions in the initiation of pre-neoplastic lesions. Specifically, acquisition of an activating Kras mutation in pancreatic acinar cells leads to upregulation of intercellular adhesion molecule-1 (ICAM-1), which serves as a chemoattractant for M1-polarized macrophages. M1 macrophages then contribute to acinar cell metaplasia and development of precancerous lesions through inflammatory cytokines and secreted proteases. PMID- 26155419 TI - Understanding high endothelial venules: Lessons for cancer immunology. AB - High endothelial venules (HEVs) are blood vessels especially adapted for lymphocyte trafficking which are normally found in secondary lymphoid organs such as lymph nodes (LN) and Peyer's patches. It has long been known that HEVs develop in non-lymphoid organs during chronic inflammation driven by autoimmunity, infection or allografts. More recently, HEVs have been observed in solid, vascularized tumors and their presence correlated with reduced tumor size and improved patient outcome. It is proposed that newly formed HEV promote antitumor immunity by recruiting naive lymphocytes into the tumor, thus allowing the local generation of cancerous tissue-destroying lymphocytes. Understanding how HEVs develop and function are therefore important to unravel their role in human cancers. In LN, HEVs develop during embryonic and early post-natal life and are actively maintained by the LN microenvironment. Systemic blockade of lymphotoxin beta receptor leads to HEV de-differentiation, but the LN components that induce HEV differentiation have remained elusive. Recent elegant studies using gene targeted mice have demonstrated clearly that triggering the lymphotoxin-beta receptor in endothelial cells (EC) induces the differentiation of HEV and that CD11c+ dendritic cells play a crucial role in this process. It will be important to determine whether lymphotoxin-beta receptor-dependent signaling in EC drives the development of HEV during tumorigenesis and which cells have HEV-inducer properties. This may reveal therapeutic approaches to promote HEV neogenesis and determine the impact of newly formed HEV on tumor immunity. PMID- 26155421 TI - Clinical relevance of miR-mediated HLA-G regulation and the associated immune cell infiltration in renal cell carcinoma. AB - In human tumors of distinct origin including renal cell carcinoma (RCC), the non classical human leukocyte antigen G (HLA-G) is frequently expressed, thereby inhibiting the cytotoxic activity of T and natural killer (NK) cells. Recent studies demonstrated a strong post-transcriptional gene regulation of the HLA-G by miR-152, -148A, -148B and -133A. Standard methods were applied to characterize the expression and function of HLA-G, HLA-G-regulatory microRNAs (miRs) and the immune cell infiltration in 453 RCC lesions using a tissue microarray and five RCC cell lines linking these results to clinical parameters. Direct interactions with HLA-G regulatory miRs and the HLA-G 3' untranslated region (UTR) were detected and the affinities of these different miRs to the HLA-G 3'-UTR compared. qPCR analyses and immunohistochemical staining revealed an inverse expression of miR-148A and -133A with the HLA-G protein in situ and in vitro. Stable miR overexpression caused a downregulation of HLA-G protein enhancing the NK and LAK cell-mediated cytotoxicity in in vitro CD107a activation assays revealing a HLA-G dependent cytotoxic activity of immune effector cells. A significant higher frequency of CD3+/CD8+ T cell lymphocytes, but no differences in the activation markers CD69, CD25 or in the presence of CD56+, FoxP3+ and CD4+ immune cells were detected in HLA-G+ compared to HLA-G- RCC lesions. This could be associated with higher WHO grade, but not with a disease-specific survival. These data suggest a miR-mediated control of HLA-G expression in RCC, which is associated with a distinct pattern of immune cell infiltration. PMID- 26155422 TI - Interferon-gamma-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression. AB - Inhibition of JAK1 or JAK2 in human tumor cells was previously shown to increase susceptibility of these cells to NK cell lysis. In the present study, we examined the cellular mechanisms that mediate this effect in hematopoietic tumor cell lines and primary tumor cells. Incubation of tumor cells with supernatant from activated NK cells or interferon-gamma (IFNgamma)-induced activation of pSTAT1 and increased expression of PD-L1 without altering expression of other activating or inhibitory NK cell ligands. These functional effects were blocked by chemical JAK inhibition or shRNAs targeting JAK1, JAK2 or STAT1. Inhibition of IFNgamma signaling also prevented the upregulation of PD-L1 and blocking PD-L1 resulted in increased tumor lysis by NK cells. These results show that NK cell activation and secretion of IFNgamma results in activation of JAK1, JAK2 and STAT1 in tumor cells, resulting in rapid up-regulation of PD-L1 expression. Increased expression of PD-L1 results in increased resistance to NK cell lysis. Blockade of JAK pathway activation prevents increased PD-L1 expression resulting in increased susceptibility of tumor cells to NK cell activity. These observations suggest that JAK pathway inhibitors as well as PD-1 and PD-L1 antibodies may work synergistically with other immune therapies by preventing IFN-induced inhibition of NK cell-mediated tumor cell lysis. PMID- 26155423 TI - Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy. AB - Melanoma is responsible for most skin cancer-related deaths and is one of the most common cancers diagnosed in young adults. In melanoma, tumors can become established by activation of the negative regulator of cytotoxic T lymphocytes (CTLs), CTL antigen-4 (CTLA-4). Ipilimumab blocks the interaction of CTLA-4 with CD80/CD86 and augments T-cell activation and proliferation. In electrochemotherapy (ECT), local application of short high-voltage pulses renders cell membranes transiently permeable to chemotherapeutic drugs. The combination of ipilimumab and ECT may be beneficial for the treatment of metastatic melanoma; however, no prospective data are available to date. Here, we report the retrospective analysis of patients treated with ipilimumab in an expanded access program (EAP) who also received ECT. Fifteen patients with previously treated metastatic melanoma who received ipilimumab 3 mg/kg every three weeks for four cycles and underwent ECT for local disease control and/or palliation of cutaneous lesions with bleomycin 15 mg/m2 after the first ipilimumab infusion were included in the analysis. Over the study period, a local objective response was observed in 67% of patients (27% complete response [CR] and 40% partial response [PR]). According to immune-related response criteria, a systemic response was observed in nine patients (five PR and four stable disease [SD]), resulting in a disease control rate of 60%. Evaluation of circulating T-regulatory (T-reg) cells demonstrated significant differences between responders and non-responders. Overall, treatment was well-tolerated and without notable toxicity. In conclusion, the combination of ipilimumab and ECT appears to be beneficial to patients with advanced melanoma, warranting further investigation in prospective trials. PMID- 26155425 TI - Immunotherapy of hematological cancers: PD-1 blockade for the treatment of Hodgkin's lymphoma. AB - The blockade of immunological checkpoints has been successfully employed for the treatment of various solid neoplasms including melanoma, mesothelioma, non-small cell lung carcinoma, and renal cell carcinoma. A recent study indicates that the vast majority of patients with advanced, heavily pretreated Hodgkin's lymphoma (HL) also respond to a monoclonal antibody targeting programmed cell death 1 (PDCD1, best known as PD-1). Thus, checkpoint blockers may soon become part of our therapeutic armamentarium against hematological tumors. This would be particularly important as it would spare (at least some) patients the deleterious toxic effects of combinatorial chemotherapies and bone marrow transplantation. We anticipate that the realm of immunotherapy will eventually conquer vast portions of the territory that now belongs to hematological malignancies. PMID- 26155424 TI - Modifications of the mouse bone marrow microenvironment favor angiogenesis and correlate with disease progression from asymptomatic to symptomatic multiple myeloma. AB - While multiple myeloma (MM) is almost invariably preceded by asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering MM (SMM), the alterations of the bone marrow (BM) microenvironment that establish progression to symptomatic disease are circumstantial. Here we show that in Vk*MYC mice harboring oncogene-driven plasma cell proliferative disorder, disease appearance associated with substantial modifications of the BM microenvironment, including a progressive accumulation of both CD8+ and CD4+ T cells with a dominant T helper type 1 (Th1) response. Progression from asymptomatic to symptomatic MM was characterized by further BM accrual of T cells with reduced Th1 and persistently increased Th2 cytokine production, which associated with accumulation of CD206+Tie2+ macrophages, and increased pro-angiogenic cytokines and microvessel density (MVD). Notably, MVD was also increased at diagnosis in the BM of MGUS and SMM patients that subsequently progressed to MM when compared with MGUS and SMM that remained quiescent. These findings suggest a multistep pathogenic process in MM, in which the immune system may contribute to angiogenesis and disease progression. They also suggest initiating a large multicenter study to investigate MVD in asymptomatic patients as prognostic factor for the progression and outcome of this disease. PMID- 26155426 TI - Immune checkpoint blockade in microsatellite instable colorectal cancers: Back to the clinic. AB - The active Th1/CTL immune microenvironment of Microsatellite Instable colorectal cancer (CRC) is counterbalanced by up-regulated expression of multiple immune checkpoints, suggesting that defective mismatch repair may be a biomarker to select CRC patients for treatment with checkpoint inhibitors. This hypothesis is currently being tested in two clinical trials. PMID- 26155427 TI - Delineating CSF-1-dependent regulation of myeloid cell diversity in tumors. AB - Myeloid cells contribute to increased malignancy and poor prognosis in breast cancer. We demonstrate that anti-CSF-1R therapy depletes a cell population sharing characteristics of tumor-associated macrophages (TAMs) and dendritic cells (DCs). Intravital imaging combined with cellular characterization has refined our understanding of anti-CSF-1R therapy on the tumor microenvironment. PMID- 26155429 TI - Implications of understanding the signaling, cellular, and cytotoxic mechanisms afforded by afucosylated antibodies. AB - Afucosylated antibodies potentiate natural killer (NK) cell-mediated antibody dependent cellular cytotoxicity (ADCC) by enhancing signaling pathways and cellular processes, which in turn, increases cytotoxic potential. Importantly, a better understanding of these processes and properties will aid in exploiting them to help design therapeutic antibodies and strategies that may be of the greatest benefit to patients. PMID- 26155428 TI - The tumoral and stromal immune microenvironment in malignant pleural mesothelioma: A comprehensive analysis reveals prognostic immune markers. AB - Antitumor immune responses against solid malignancies correlate with improved patient survival. We conducted a comprehensive investigation of immune responses in tumor and tumor-associated stroma in epithelioid malignant pleural mesothelioma with the goal of characterizing the tumor immune microenvironment and identifying prognostic immune markers. We investigated 8 types of tumor infiltrating immune cells within the tumor nest and tumor-associated stroma, as well as tumor expression of 5 cytokine/chemokine receptors in 230 patients. According to univariate analyses, high densities of tumoral CD4- and CD20 expressing lymphocytes were associated with better outcomes. High expression of tumor interleukin-7 (IL-7) receptor was associated with worse outcomes. According to multivariate analyses, stage and tumoral CD20 detection were independently associated with survival. Analysis of single immune cell infiltration for CD163+ tumor-associated macrophages did not correlate with survival. However, analysis of immunologically relevant cell combinations identified that: (1) high CD163+ tumor-associated macrophages and low CD8+ lymphocyte infiltration had worse prognosis than other groups and (2) low CD163+ tumor associated macrophages and high CD20+ lymphocyte infiltration had better prognosis than other groups. Multivariate analyses demonstrated that CD163/CD8 and CD163/CD20 were independent prognostic factors of survival. With a recent increase in immunotherapy investigations and clinical trials for malignant pleural mesothelioma patients, our observations that CD20+ B lymphocytes and tumor-associated macrophages are prognostic markers provide important information about the tumor microenvironment of malignant pleural mesothelioma. PMID- 26155430 TI - CD14+ macrophage-like cells as the linchpin of cervical cancer perpetrated immune suppression and early metastatic spread: A new therapeutic lead? AB - A number of studies point to an aberrant differentiation and accumulation of CD14+ PD-L1+ M2-macrophage-like cells in the microenvironment of cervical cancer, which promote immunosuppressive conditions and are associated with tumor invasion, angiogenesis and metastasis. Therapeutic targeting of these macrophages may tip the balance in favor of antitumor immunity. Cervical cancer is the fourth most common cancer among women worldwide and is caused by a persistent infection and subsequent integration of high-risk types of the human papillomavirus. Continuous expression of the viral oncoproteins E6 and E7 has been shown essential to maintain the transformed state of infected keratinocytes. As these non-self oncoproteins are immunogenic, cervical cancer requires a highly immune suppressed tumor microenvironment to metastasize through lymphovascular space invasion (LVSI) to the pelvic tumor-draining lymph nodes (TDLN). Unraveling the mechanisms underlying this immune suppression may uncover novel therapeutic targets aimed at loco-regional control of cervical cancer. PMID- 26155431 TI - Improving clinical benefit for prostate cancer patients through the combination of androgen deprivation and immunotherapy. AB - Androgen-deprivation therapy (ADT) induces prostate cancer immunogenic modulation (IM) by reducing human tumor cell expression of anti-apoptotic genes thus facilitating increased sensitivity to immune-mediated lysis. Through its stimulation of IM, ADT has been shown to synergize with active immunotherapy thereby significantly improving overall survival in a mouse model of prostate cancer. PMID- 26155432 TI - Regramming myeloid responses to improve cancer immunotherapy. AB - Infiltration by immunosuppressive myeloid cells helps tumors to overcome immune surveillance and can render patients less responsive to therapeutic intervention. Several recent studies have demonstrated that reprogramming myeloid responses can effectively enhance cancer immunotherapy, suggesting several new potential combination therapies for clinical testing. PMID- 26155433 TI - Glycyrrhizin down-regulates CCL2 and CXCL2 expression in cerulein-stimulated pancreatic acinar cells. AB - Many inflammatory chemokines release from leukocytes and pancreatic acinar cells which play important roles in pathophysiology of acute pancreatitis (AP). Of interests, CXCL2 and CCL2 have been shown elevated in the plasma of patients with AP. We have recently found that Glycyrrhizin (GZ) attenuates AP in mice model. In this study, we aimed to investigate the direct effect of GZ on expression levels of CCL2 and CXCl2 in isolated pancreatic acinar cells. Isolated acinar cells were isolated from the pancreas of healthy C57BL/6 mice, stimulated with cerulein (10( 7) M) and then treated with either PBS or different doses of GZ. The levels of CCL2 and CXCL2 expression at mRNA were assessed by qRT-PCR. Conditioned media from supernatants of each cells culture condition were collected for detection of CCL2 and CXCL2 levels by ELISA. First, we observed that cerulein significantly upregulates both cytokines expression in acinar cells. Moreover, we treated the acinar cells with GZ and found that GZ significantly downregulates CCL2 and CXCL2 expression at mRNA levels in a dose-dependent manner. Consistently, the conditioned media of GZ-treated cells contained a significant lower levels of CCL2 and CXCL2 (p<0.05). In conclusion, our data demonstrate for the first time that GZ directly downregulates CCL2 and CXCL2 levels in cerulein-stimulated acinar cells which may explain the mechanism of therapeutic effects of GZ in cerulein-induced AP in mice. PMID- 26155434 TI - Investigation of IL-21 gene polymorphisms (rs2221903, rs2055979) in cases with multiple sclerosis of Azerbaijan, Northwest Iran. AB - BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System that is immunologically mediated in genetically susceptible individuals. IL-21, a cytokine produced by TCD4(+) cells, particularly by Th-17 cells, is believed to play an important role in the MS pathogenesis. OBJECTIVE: This study was performed to investigate the impact of genetic polymorphisms in IL-21 gene on MS susceptibility and clinical profiles. METHODS: Seventy Iranian patients with clinically definite relapsing-remitting MS and 110 age, sex and ethic matched controls were genotyped for IL-21 gene polymorphisms using PCR-RFLP method. RESULTS: Our results showed that the IL-21 rs2221903 SNP is not polymorphic in our population. Also, the allelic and genotypic frequencies of the IL-21 rs2055979 did not differ significantly between the MS patients and controls (P = 0.413 and P = 0.565 respectively, and OR = 1.122, 95% CI = 0.79-1.87 for T allele). However, our results showed that IL-21 rs2055979 (G/T) T allele positive (TT+GT) MS patients had lower (PI <= 1.5) disease progression compared to rs2055979 T allele negative (GG) patients (P = 0.009). CONCLUSION: Our results showed that no outstanding association exists between IL-21 alleles and susceptibility to MS. However, our clinical analysis showed significant association of IL-21 gene polymorphism with the progression of multiple sclerosis disease. Our results indicate that the G allele promotes, or the T allele protects against disease progression. To clarify the role of IL-21 rs2055979 in MS pathogenesis, further comprehensive studies with larger sample sizes among different ethnicity populations are recommended. PMID- 26155435 TI - Does Age Influence Bariatric Surgery Outcomes? AB - Aim: The purpose of this study was to evaluate presurgical comorbidities, perioperative and postoperative complications, and postsurgical outcomes of minimally invasive bariatric surgery in patients aged 55 years and older to determine if age should be used as a selection criteria for bariatric surgery. Methods: A total of 750 patients underwent sleeve gastrectomy or robotic-assisted Roux-en-Y gastric bypass from January 2008 to June 2014. Patients were divided into three groups according to age: <55 years old; >=55 to <65 years old; and >=65 years old. Demographics, presurgical comorbidities, perioperative and postoperative complications (leaks or conversions to open surgery), and postsurgical outcomes were compared across the different groups. Results: Significant differences in presurgical comorbidities were found across age groups (p<0.001). Results from descriptive statistics revealed that patients younger than 55 years of age had a greater number of complications-defined as leaks (n=1) or conversions to open surgery (n=2)-than did patients older than 55 years of age. There were no significant differences across age groups regarding length of stay. Linear regression analysis failed to reveal significant associations between age and percentage excess weight loss at 6, 12, and 24 months follow-up. Conclusions: These initial results suggest that patient selection for bariatric surgery should not be based on age alone. PMID- 26155436 TI - Predictors of Postoperative Aftercare Attrition among Gastric Bypass Patients. AB - Background: Poor adherence to post-bariatric surgery aftercare continues to challenge surgical practices. The objective of this study was to identify factors that predict poor aftercare attendance among patients who underwent Roux-en-Y Gastric Bypass (RYGB) surgery. Method: A retrospective medical chart review of patients who underwent RYGB from 2002 to 2011 was conducted. Patients with four visits or more in the first 2 years (>50%) were categorized as "acceptable follow up" and with <=50% as "poor follow-up." Demographics, presurgical body mass index (BMI), and comorbidities were compared using multivariate analysis. Results: Out of 2,658 patients, 1,092 (41.1%) had acceptable follow-up. Preoperative factors that predicted acceptable follow-up included female gender (odds ratio [OR] 1.41 [95% confidence interval (CI) 1.15-1.72]), older age (OR 1.03 [95% CI 1.03 1.04]), higher BMI at surgery (OR 1.02 [95% CI 1.01-1.03]), and Hispanic ethnicity (OR 1.40 [95% CI 1.15-1.72]). Conversely, presence of diabetes mellitus (OR 0.58 [95% CI 0.39-0.88]), hypertension (OR 0.53 [95% CI 0.39-0.72]), and obstructive sleep apnea (OR 0.39 [95% CI 0.26-0.57]) predicted less adherence to RYGB aftercare. Conclusion: These findings suggest RYGB patients' age, gender, ethnicity, preoperative BMI, and certain comorbidities should be considered to maximize postoperative aftercare attendance. PMID- 26155437 TI - Association between societal costs and treatment response in children and adolescents with ADHD and their parents. A cross-sectional study in the Netherlands. AB - Attention Deficit Hyperactivity Disorder (ADHD) is associated with considerable burden of illness at a patient, family and societal level. Although pharmacological treatment is recommended by authoritative guidelines, evidence on its influence on the broader burden of illness is limited. As treatment induces costs, proper healthcare decision making requires evidence on the associated societal costs or benefits and particularly the difference that response to treatment can make. Data on ADHD related resource use of patients 8-18 years and parents were collected by means of a cross-sectional, online survey amongst members of the Dutch parent association. Children were stratified to responders and non-responders to treatment according to pre-defined expert definitions. Analyses were performed on 618 questionnaires (428 responders; 190 non-responders to treatment). Children were 11.8 years on average and mainly boys (82 %). Total monthly costs for children were ?578 and ?839 for responders and non-responders, respectively (p = 0.021), with a breakdown to direct medical costs (?322 vs. ?512; p = 0.068), direct non-medical costs (?222 vs. ?296; p = 0.090), and indirect non-medical costs (?34 vs. ?57; p < 0.001). For parents, total costs were ?246 vs. ?399 for the responding and non-responding children, respectively (p = 0.006), with a breakdown to direct medical costs (?130 vs. ?211; p = 0.010) and indirect non-medical costs (?116 vs. ?181; p = 0.092). Total monthly costs of children and their parents together were ?824 and ?1228 for responders and non responders to treatment, respectively (p = 0.002). These results stress the importance of a focus on response to treatment, not only beneficial for patients and their family, but also resulting in considerable societal benefits. PMID- 26155438 TI - Predictors of anemia in a multi-ethnic chronic kidney disease population: a case control study. AB - Anemia is a common complication of chronic kidney disease (CKD). However, risk factors of anemia in CKD patients in Singapore are not well established. Hence, a retrospective, case-control study involving non-dialysis CKD patients was conducted to determine possible predictors of anemia in the local CKD population. Non-dialysis adult CKD patients, not receiving renal replacement therapy or erythropoiesis-stimulating-agents were included. Parameters collected included demographics e.g. age, sex and race; clinical data e.g. CKD stage and medical/medication histories; and laboratory data e.g. serum electrolytes, urinary and hematologic parameters. Patients were classified as anemic or non anemic using a threshold hemoglobin level of 10 g/dL. The parameters were evaluated for their predictive value for anemia development using multivariate logistical regression and calculation of odds ratios. Statistical analyses were performed using STATA. A total of 457 patients (162 anemic and 295 non-anemic) were analysed. Multivariate analysis showed that probability of developing anemia was greater for patients with stage 5 CKD (OR 16.76, p < 0.001), with hematological disorders (OR 18.61, p < 0.001) and with respiratory disorders (OR 4.54, p = 0.004). The probability of developing anemia was lower for patients with higher previous hemoglobin concentration (OR 0.32, p < 0.001) and in those receiving iron supplements (OR 0.44, p = 0.031). Gender and race were not found to be significant predictors of anemia. Risk of anemia is increased in patients with advanced CKD, haematological disorders, respiratory disorders, and those not taking iron supplements. This study has increased our understanding of the patient subgroups at risk for anemia. PMID- 26155439 TI - Vertical distribution of dioxins in soil of Bien Hoa airbase, Vietnam. AB - Bien Hoa airbase is a known dioxin-contaminated hotspot in Vietnam. The contamination occurred during the Vietnam War at the site where dioxins were transported, stored, sprayed, and spilled in the area. Dioxins, which are cancer inducing substances, may transfer from the soil to food crops and finally to human beings living around the area. Many surveys of dioxins in soil, water, organisms, and human have been carried out in this study area since 2002. In this paper vertical distribution of dioxins in undisturbed soil cores were examined. Twelve soil samples from three drilled cores were collected to analyze dioxin levels according to the standard Japanese analytical method. The results showed that the toxicity equivalency quantity (TEQ) in one soil sample at a depth of 2.6 m reached 3,300 pg-TEQ/g-dw. High TEQs were also observed in the clay layer. This anomaly of dioxin concentrations could be attributed to the affinity of dioxins for the clay layer. The isomer patterns in the soils were different from those in the soil of Hokkaido in that 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) was the most dominant in the soil sample. This indicates that the dioxins originate from a defoliant Agent Orange disposed at the site after the Vietnam War. PMID- 26155440 TI - Automatic summarization of soccer highlights using audio-visual descriptors. AB - Automatic summarization generation of sports video content has been object of great interest for many years. Although semantic descriptions techniques have been proposed, many of the approaches still rely on low-level video descriptors that render quite limited results due to the complexity of the problem and to the low capability of the descriptors to represent semantic content. In this paper, a new approach for automatic highlights summarization generation of soccer videos using audio-visual descriptors is presented. The approach is based on the segmentation of the video sequence into shots that will be further analyzed to determine its relevance and interest. Of special interest in the approach is the use of the audio information that provides additional robustness to the overall performance of the summarization system. For every video shot a set of low and mid level audio-visual descriptors are computed and lately adequately combined in order to obtain different relevance measures based on empirical knowledge rules. The final summary is generated by selecting those shots with highest interest according to the specifications of the user and the results of relevance measures. A variety of results are presented with real soccer video sequences that prove the validity of the approach. PMID- 26155441 TI - Nimesulide induced leukocytoclastic vasculitis and hepatitis: a case report. AB - BACKGROUND: Nimesulide is a non-steroidal anti-inflammatory drug with antipyretic and analgesic properties, which is still used in many countries despite its known hepatotoxicity. Along with hepatotoxicity it has also been associated with several other Adverse Drug Reactions (ADRs) including leukocytoclastic vasculitis (LCV). CASE DESCRIPTION: A 38 year-old female presented with history of acute onset fever for which she took tablet nimesulide and paracetamol combination (100 mg Nimesulide + 500 mg paracetamol tablet), 1 tab three times daily for 4 days, following which she developed rash all over the body. She also had clinical and biochemical evidence of acute hepatitis. Histopathological examination of the skin rash documented the presence of LCV. She was managed symptomatically with anti-inflammatory and supportive therapy and was not further exposed to nimesulide. DISCUSSION AND EVALUATION: Our case demonstrates occurrence of acute hepatitis and LCV associated with nimesulide intake. The case meets the defining criteria for the diagnosis of LCV preceded by history of nimesulide intake. There was also clinical and biochemical evidence of hepato-cellular damage which supports the concurrent development of hepatitis along with the development of LCV following nimesulide use. To the best of our knowledge there is no previous published report of LCV and hepatitis occurring concurrently in the same patient following nimesulide intake. Nimesulide should be added to the list of agents associated with these serious adverse drug reactions. CONCLUSIONS: Nimesulide has been a contentious drug over many years. Under such evidence of serious ADRs the scientific community should consider ensuring strict pharmacovigilance with respect to its use especially in the developing countries where such monitoring systems are inadequate. PMID- 26155442 TI - The effect of anastrozole on bone mineral density during the first 5 years of adjuvant treatment in postmenopausal women with early breast cancer. AB - PURPOSE: The administration of aromatase inhibitors is associated with bone loss in postmenopausal women. We assessed changes in bone mineral density (BMD) from baseline to 60 months of treatment in patients receiving anastrozole as initial adjuvant therapy. METHODS: Postmenopausal women with hormone receptor-positive breast cancer receiving anastrozole as adjuvant therapy at our center since 2004 were enrolled in this study. BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24, 36, 48 and 60 months. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis having a T score of -2.5 or lower. RESULTS: Fifty-five patients were enrolled in the study between 2004 and 2011, and the mean follow-up period was 53.6 months. Thirty-five patients were administered Bis (risedronate in 27 patients, alendronate in 8 patients). After 6 months of hormone therapy, BMD decreased by 0.5% from baseline at the lumbar spine (LS) and BMD decreased by 1.5% at the femoral neck (FN). However, BMD increased by 1.9% at the LS and BMD decreased by 1.5% at the FN for 60 months of treatment. In patients treated with upfront Bis (n = 19), 5.4% BMD increase from baseline was noted at the LS whereas in those without Bis (n = 21) BMD decreased by 4.3% from baseline within 24 months (P < 0.0001). Fractures were observed in 4 patients (7.3%), and 1 patient (1.8%) had a fragility fracture. CONCLUSIONS: Upfront treatment of Bis with anastrozole significantly increased BMD at the LS and an optimal use of Bis would not increase bone fractures. TRIAL REGISTRATION: UMIN0000017571. PMID- 26155443 TI - Exploring the patterns of alpine vegetation of Eastern Bhutan: a case study from the Merak Himalaya. AB - A survey was conducted from March to September 2012 along the altitudinal gradient of the Jomokungkhar trail in the Merak Himalaya of Sakteng Wildlife Sanctuary to study the floristic compositions and the patterns of alpine vegetation of Eastern Bhutan. The vegetation of the sampled plots is classified into five types of communities based on the hierarchical cluster analysis at similarity index 63% viz., (1) Riverine Community; (2) Abies-Rhododendron Woodland Community; (3) Juniperus Scrub Community; (4) Rhododendron Krummholz and (5) Alpine Meadow, based on the floristic compositions. In addition, it was noticed that the fragile alpine environment of the Merak Himalaya has high plant diversity and important plants that are susceptible to the anthropogenic pressures. PMID- 26155444 TI - Gallbladder torsion within incisional hernia: an original cholecystitis. AB - Gallbladder torsion with ischemic wall necrosis is a rare condition, as gallbladder herniation. We describe here an original case of a patient with a symptomatic incisional hernia containing a gangrenous gallbladder twisted about its pedicle. We report preoperative findings on CT-scan and emergency surgical management. PMID- 26155445 TI - Treatment strategies for treatment naive HIV patients in Germany: evidence from claims data. AB - A recent observational study of HIV patients in Germany suggests that treatment naive patients that are in a more advanced stage of their disease are more likely to receive a treatment regimen based on a boosted protease inhibitor (PI/r) compared with a non-nucleoside reverse-transcriptase-inhibitor (NNRTI) base regimen. To validate those results we analysed claims data of seven German sickness funds from 2009 to 2012 with approximately 4 million beneficiaries. Patients in a more advanced disease state (CDC class C) had a higher likelihood to receive a PI/r based regime rather than a NNRTI based regimen as their initial treatment. There was also a significant correlation between PI/r based regimen and number of comorbidities but not with age. Our results confirm a highly significant relationship between being in a more severe stage of HIV disease and a PI/r based treatment regimen. PMID- 26155446 TI - Vascular tumors of the external auditory canal: three case reports and a review of the literature. AB - BACKGROUND: Benign vascular tumors are frequently found in the head and neck, however, such tumors of the external auditory canal are extremely rare. We report three cases of benign vascular tumors limited to the external auditory canal. CASE DESCRIPTION: A 50-year-old woman was diagnosed during an episode of ear fullness and hearing loss. A 10-year-old boy consulted our department about an episode of recurrent otorrhagia. A 20-year-old man found a bulge of his external auditory canal by chance. Complete surgical resection was performed for the first patient. The second patient underwent electro-coagulation of the lesion. In the third patient, to exclude the possibility of a malignant tumor, a biopsy was performed under local anesthesia. Histopathological analysis demonstrated the characteristic of vascular tumors. The lesion showed remarkable reduction during his treatment with antibiotics and cleaning. He remains under careful observation. DISCUSSION AND EVALUATION: In diagnosis, there is sometimes confusion between vascular tumors and malformations. Generally, vascular malformations can be differentiated from vascular tumors since they are present at birth and are generally stable. CONCLUSION: Decision making about treatment of benign vascular tumors is sometimes confusing because of the difficulty in diagnosis. We performed biopsy for only one of our three cases because we regard that informal biopsy should not be conducted for lesions with difficult hemostic conditions and locations. PMID- 26155447 TI - Effect of exercise-induced muscle damage on muscle hardness evaluated by ultrasound real-time tissue elastography. AB - PURPOSE: To assess the effect of exercise-induced muscle damage on muscle hardness and evaluate the relationship between muscle hardness and muscle damage indicators. METHODS: Seven men (mean 25.3 years; 172.7 cm; 66.8 kg) performed the single-leg ankle plantar flexion exercise involving both concentric and eccentric contractions (10 sets of 40 repetitions). The hardness of the medial gastrocnemius (MG) was evaluated using ultrasound real-time tissue elastography before, from day 1 to 4, and day 7 after exercise. The strain ratio between the MG and a reference material was calculated. Simultaneously, we evaluated the magnetic resonance T2 value (an index of edema) of the triceps surae, the ankle dorsiflexion range of motion (ROM), and calf muscle soreness. Serum creatine kinase activity was assessed before, 2 and 4 h, and from day 1 to 4 after exercise. RESULTS: The MG showed lower strain ratio, indicating increased muscle hardness, on day 4 post-exercise (P < 0.01) and higher T2 values on days 1-7 post exercise (P < 0.01) relative to each pre-exercise value. The ankle dorsiflexion ROM was lower on days 2-4 post-exercise (P < 0.01). The serum creatine kinase markedly increased on days 3 and 4 post-exercise (not significant). The degree of muscle soreness among the post-exercise time points was similar. The decreased strain ratio did not correlate with the increased T2, the decreased joint ROM or muscle soreness. CONCLUSION: Muscle hardness increased after strenuous resistance exercise, but the change was not related with muscle edema, decreased joint ROM, or muscle soreness resulting from muscle damage. PMID- 26155448 TI - The sit up test to exhaustion as a test for muscular endurance evaluation. AB - AIMS/HYPOTHESIS: The aim of this study was to examine the sit up test to exhaustion as a field test for muscular endurance evaluation in a sample of sedentary people of both sexes. METHODS: A cross-sectional study was performed. Three-hundred-eighty-one participants volunteered for the study (28.5 +/- 10.0 years; 168.2 +/- 8.9 cm; 65.1 +/- 11.1 kg), of which 194 males (27.5 +/- 10.2 years; 173.6 +/- 7.0 cm; 71.2 +/- 5.2 kg) and 187 females (29.6 +/- 10.1 years; 162.6 +/- 7.1 cm; 58.7 +/- 8.9 kg). Each subject voluntarily and randomly performed: a sit up test (SUT), a push up test (PUT), and a free weight squat test (ST), all till exhaustion. A multiple regression analysis was adopted for data analysis. Subsequently a percentile model for muscle endurance was developed. The 25th, 50th, and 75th percentile were identified as upper limit for low muscular endurance, average muscular endurance, and lower limit for high muscular endurance, respectively. RESULTS: Considering the sit up test as the dependent variable, the coefficients (R(2) = 0.23; r = 0.49; p < 0.001), and (R(2) = 0.31; r = 0.57; p < 0.001) emerged from a multiple regression analysis applied with respect to the push up test and the squat test, respectively. Gender stratification showed regression coefficients of (R(2) = 0.19; r = 0.44; p < 0.001) for SUT vs. PUT, and (R(2) = 0.30; r = 0.56; p < 0.001) for SUT vs. ST in male; and (R(2) = 0.23; r = 0.49; p < 0.001) for SUT vs. PUT, and (R(2) = 0.34; r = 0.59; p < 0.001) for SUT vs. ST in female. CONCLUSIONS/INTERPRETATION: The SUT showed low inter-relation with the other proposed tests indicating that the adoption of a single test for the global evaluation of muscle endurance is not the optimal approach. Moreover, the SUT was found to be inexpensive, safe, and appropriate for core muscle endurance measurement for both male and female. PMID- 26155450 TI - Towards a web-based archaeological excavation platform for smartphones: review and potentials. AB - The paper conducts a review questioning the usability of a web-based platform supporting archaeological excavations and related fields, which will execute on smartphones. Based on the thorough review and comparison of related work, the basic features of such a platform are outlined. The platform should support documenting content on an underlying XML database through a content management system, producing and exchanging notes, map interaction, use of a shared whiteboard, collaboration among archaeologists etc. The architecture of the platform is presented along with two case studies supporting usual practices on an archaeological field, some primary evaluation results and future work. PMID- 26155449 TI - Effect of training in hypoxia on repeated sprint performance in female athletes. AB - BACKGROUND: This study determined the effect of repeated sprint training in hypoxia (RSH) in female athletes. METHODS: Thirty-two college female athletes performed repeated cycling sprints of two sets of 10 * 7-s sprints with a 30-s rest between sprints twice per week for 4 weeks under either normoxic conditions (RSN group; FiO2, 20.9%; n = 16) or hypoxic conditions (RSH group; FiO2, 14.5%; n = 16). The repeated sprint ability (10 * 7-s sprints) and maximal oxygen uptake ([Formula: see text]) were determined before and after the training period. RESULTS: After training, when compared to pre-values, the mean power output was higher in all sprints during the repeated sprint test in the RSH group but only for the second half of the sprints in the RSN group (P <= 0.05). The percentage increases in peak and mean power output between before and after the training period were significantly greater in the RSH group than in the RSN group (peak power output, 5.0 +/- 0.7% vs. 1.5 +/- 0.9%, respectively; mean power output, 9.7 +/- 0.9% vs. 6.0 +/- 0.8%, respectively; P < 0.05). [Formula: see text] did not change significantly after the training period in either group. CONCLUSION: Four weeks of RSH further enhanced the peak and mean power output during repeated sprint test compared with RSN. PMID- 26155451 TI - Low-molecular-weight chitosan scavenges methylglyoxal and N (epsilon) (carboxyethyl)lysine, the major factors contributing to the pathogenesis of nephropathy. AB - Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction. Accumulation of MG and its downstream metabolite N (epsilon) (carboxyethyl)lysine (CEL) has been identified in several variations of nephropathy, including diabetic, hypertensive, and gentamicin-induced nephropathies. In this study, we investigated the effects of low-molecular-weight chitosan (lmw-chitosan) on MG-induced carbonyl stress in aristolochic acid induced nephropathy. We used a buffer to investigate whether MG could be scavenged by lmw-chitosan in vitro. In addition, we also used a mouse model of aristolochic acid-induced nephropathy, which exhibits 12-fold greater accumulation of MG in the kidneys than that found in control animals, to examine whether lmw-chitosan could decrease MG levels in vivo. Examination of the binding of lmw-chitosan with MG in vitro demonstrated that the concentration of lmw chitosan necessary to achieve 50% inhibition was 4.60 ug mL(-1). Treatment with lmw-chitosan (500 mg kg(-1) day(-1) orally) for 14 days significantly decreased renal MG accumulation from 212.86 +/- 24.34 to 86.15 +/- 33.79 ug g(-1) protein (p < 0.05) and CEL levels from 4.60 +/- 0.27 to 2.84 +/- 0.28 umol ug(-1) protein (p < 0.05) in the aristolochic acid-induced nephropathy model. These data suggest that lmw-chitosan might represent a novel treatment modality for MG-related diseases such as nephropathy. PMID- 26155452 TI - Pure ultrasonography-guided radiation-free percutaneous nephrolithotomy: report of 357 cases. AB - PURPOSE: To assess the safety and effectiveness of pure ultrasound-guided percutaneous nephrolithotomy. PATIENTS AND METHODS: Three hundred fifty-seven patients were treated; 139 women and 218 men, with a mean age of 33.7 years (range 21-69 years) and a mean stone size of 33.5 mm in maximum diameter (range 20-52 mm). Stone locations were renal pelvis (174), lower calyx (68) or both (115) with mild to moderate hydronephrosis seen on excretory urography. A ureteral stent was inserted by cystoscope, and saline was injected for better localization of the pelvicaliceal system (PCS), if needed. Puncture of the PCS was done by an 18-gauge nephrostomy needle through the lower pole calyx, and all the steps, including dilatation, were done under the guidance of ultrasonography. RESULTS: The day after the operation, 318 (89.07%) patients were stone-free in the kidneys, ureters, and bladder x-rays. Nineteen patients (5.3%) had multiple fragments that measured equal or less than 5 mm and passed them spontaneously in 2-4 weeks (total stone-free rate 94.4%). Access failure occurred in ten obese patients (2.8%) and fluoroscopy was required. Residual fragments with sizes of 10 12 mm were seen in seven patients, all of who underwent shock wave lithotripsy. In one patient, a fragment measuring 7-8 mm migrated into the distal part of the ureter. It was fragmented with ureteroscopy and pneumatic lithoclast 2 days after the operation. In two patients who had large (>15 mm) residual stone redo percutaneous nephrolithotomy was performed 48 h after the first procedure. CONCLUSION: Percutaneous nephrolithotomy guided by ultrasonography seems to be as effective as fluoroscopy in selected cases and poses no risk of surgeon and patient exposure to radiation; however, more experience is required. PMID- 26155453 TI - Bacteriological profile and antimicrobial susceptibility patterns of blood culture isolates among febrile patients in Mekelle Hospital, Northern Ethiopia. AB - Bacterial bloodstream infections are a major public health problem, which leads to high morbidity and mortality of patients. On time diagnosis and appropriate medication will be the best way to save the lives of affected ones. The aim of the present study was to determine the bacterial profile of bloodstream infections and their antibiotic susceptibility pattern in Mekelle Hospital. Cross sectional study method was carried out in 514 (269 females and 245 males) febrile patients in Mekelle hospital from March to October 2014. Standard bacteriological methods were used for blood collection, bacterial isolation and antimicrobial susceptibility pattern. Out of the total 514 febrile patients, 144 (28%) culture positive were isolated. Staphylococcus aureus 54 (37.5%), Coagulase-negative staphylococci 44 (30.6%), Escherichia coli 16 (3.1%), Citrobacter spp. 9 (1.7%) and Salmonella typhi 8 (1.6%) were the most dominant isolates, collectively accounting for >90% of the isolates. Antimicrobial resistance pattern for gram positive and gram negative bacteria was 0-83.3% and 0-100%, respectively. High resistance was seen to Trimethoprim-sulphamethoxazole 101 (70.1%), Oxacillin 65 (62.5%), Ceftriaxone 79 (58.9%) and Doxycycline 71 (49.3%). Fifty-nine percent of the isolated bacteria in this study were multi drug resistant. Most bacterial isolates were sensitive to Gentamicin, Ciprofloxacin and Amoxicillin clavulanic acid. All gram positive isolates in this current study were sensitive to vancomycin. Prevalence of bacterial isolates in blood was high. It also reveals isolated bacteria species developed multi drug resistance to most of the antibiotics tested, which highlights for periodic surveillance of etiologic agent, antibiotic susceptibility to prevent further emergence and spread of resistant bacterial pathogens. PMID- 26155454 TI - Antidiabetic, antioxidant, antihyperlipidemic effect of extract of Euryale ferox salisb. with enhanced histopathology of pancreas, liver and kidney in streptozotocin induced diabetic rats. AB - BACKGROUND: Ethanolic extract of Euryale ferox salisb. (EFx) may have an effect on the activity of hepatic antioxidant enzymes, glycemic control and lipid profile and histopathology of pancreas, liver and kidney of streptozotocin (STZ) induced diabetic wistar rats. METHODS: Wistar albino rats were divided into eight groups viz. non-diabetic (normal control), diabetic control (STZ-induced), diabetic treated (infused with different doses of Euryale ferox. Salisb. ethanolic extract) and diabetic conventional treated (treated with Glibenclamide). Diabetes was induced by administering streptozotocin (60 mg/kg body weight) intraperitoneal (i.p). The ethanolic extract was supplemented in different doses through oral route. Biochemical investigations were carried out according to previously reported methods. Histopathological examinations were done accordingly. RESULTS: The EFx supplemented diabetic rats significantly (p < 0.001) decreased the blood glucose level in a dose dependent manner. Plasma insulin level was significantly increased in EFx treated rats. The hepatic gluconeogenic enzymes activities were restored to normal in EFx treated rats. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) were significantly increased (p < 0.001) among EFx treated rats. Lipid profile was reinstated to nearly normal level among EFx treated rats. Histopathological investigations revealed that microscopic architecture of pancreatic, hepatic and renal cells improvised in EFx treated diabetic rats. CONCLUSION: EFx supplement could improve the glycemic control as well as lipid profile in diabetic rats along with improvised antioxidant enzymes which has beneficial effect in preventing the diabetic complications by scavenging the free radicals in diabetic rats. PMID- 26155455 TI - Phase III, randomized, double-blind, placebo-controlled, multicenter study of lipegfilgrastim in patients with non-small cell lung cancer receiving myelosuppressive therapy. AB - PURPOSE: The aim of this study was to demonstrate lipegfilgrastim superiority versus placebo in adults with non-small cell lung cancer receiving myelosuppressive chemotherapy. METHODS: This phase III, double-blind study randomized chemotherapy-naive patients to receive cisplatin and etoposide with either lipegfilgrastim 6 mg or placebo. Because of the placebo control, patients at individual high risk for febrile neutropenia (FN; >=20%) were excluded. Study drug was administered on day 4 (24 h after chemotherapy) of a 21-day cycle for <=4 cycles. Primary efficacy measure was FN incidence in cycle 1. Secondary assessments included duration of severe neutropenia (DSN), absolute neutrophil count (ANC) profile, and adverse events (AEs). RESULTS: The study included 375 patients (lipegfilgrastim, n = 250; placebo, n = 125). Lipegfilgrastim superiority for FN incidence in cycle 1 was not achieved but incidence was lower (2.4%) versus placebo (5.6%). Cycle 1 mean DSN was significantly shorter for lipegfilgrastim (0.6 +/- 1.1 days) versus placebo (2.3 +/- 0.5 days; p < 0.0001). Incidence of severe neutropenia was significantly lower for lipegfilgrastim versus placebo overall and in each cycle (all, p < 0.0001). Mean ANC nadir was lowest in cycle 1 but significantly higher for lipegfilgrastim (1.60 +/- 1.64) than placebo (0.67 +/- 0.85; p < 0.0001). Mean time to ANC recovery was shorter with lipegfilgrastim in each cycle. Treatment-emergent AEs were similar between treatment groups. CONCLUSIONS: Lipegfilgrastim was not statistically superior to placebo for incidence of FN in cycle 1, but was more effective in reducing incidence of severe neutropenia, DSN, and time to ANC recovery, with an acceptable safety profile. Controlled-trials.com identifier: ISRCTN55761467. PMID- 26155456 TI - Left frontal glioma induces functional connectivity changes in syntax-related networks. AB - BACKGROUND: A glioma leads to a global loss of functional connectivity among multiple regions. However, the relationships between performance/activation changes and functional connectivity remain unclear. Our previous studies (Brain 137:1193-1212; Brain Lang 110:71-80) have shown that a glioma in the left lateral premotor cortex or the opercular/triangular parts of the left inferior frontal gyrus causes agrammatic comprehension accompanied by abnormal activations in 14 syntax-related regions. We have also confirmed that a glioma in the other left frontal regions does not affect task performances and activation patterns. RESULTS: By a partial correlation method for the time-series functional magnetic resonance imaging data, we analyzed the functional connectivity in 21 patients with a left frontal glioma. We observed that almost all of the functional connectivity exhibited chaotic changes in the agrammatic patients. In contrast, some functional connectivity was preserved in an orderly manner in the patients who showed normal performances and activation patterns. More specifically, these latter patients showed normal connectivity between the left fronto-parietal regions, as well as normal connectivity between the left triangular and orbital parts of the left inferior frontal gyrus. CONCLUSIONS: Our results indicate that these pathways are most crucial among the syntax-related networks. Both data from the activation patterns and functional connectivity, which are different in temporal domains, should thus be combined to assess any behavioral deficits associated with brain abnormalities. PMID- 26155457 TI - A rare case of intramedullary 'whorling-sclerosing' variant meningioma. AB - A 52-year-old man with a seven-year history of progressive weakness, gait problems, and pain in his extremities presented with subacute worsening of his symptoms. Examination revealed weakness in all four extremities, increased tone, hyperreflexia, and sensory deficits. MRI of the cervical spine showed an area of signal abnormality and abnormal enhancement within the cervical cord at the C5-C6 level. The patient initially underwent biopsy followed a few days later by a debulking surgery. Postoperatively, the patient showed improvement in strength as well as ambulation. Intraoperatively, the lesion was confirmed to be intramedullary without any dural attachments. Histopathological examination revealed an extensively hyalinized tumor with sparse collections of cells that were immunopositive for both cytokeratin and GFAP, and immunonegative for EMA and progesterone receptor. This is an unusual pattern of expression, with cytokeratin immunopositivity suggesting a meningioma and GFAP immunopositivity suggesting a glioma. Considering the combination of extensive hyalinization with cytokeratin positivity the tumor was thought to be most consistent with a hyalinized meningioma with GFAP positivity. GFAP-positive meningiomas are rare, and these include the recently described 'whorling-sclerosing' variant. Only three cases of this tumor have been previously reported, all of which were intracranial. This is the first reported case of an intramedullary whorling-sclerosing meningioma. PMID- 26155458 TI - Impact of coping with interpersonal stress on the risk of depression in a Japanese sample: a focus on reassessing coping. AB - Reassessing coping, a concept first proposed in Asia, refers to efforts to wait patiently for an appropriate opportunity to act or for a change or improvement in a situation, and can be observed in individuals facing stressful relationship events. The main purpose of the present study was to determine if reassessing coping would be associated with a lower risk of depression. The author examined the relationships between depression risk using the Center for Epidemiologic Studies Depression Scale (CES-D) and coping strategies for interpersonal stressors, including reassessing coping, in a sample of 1,912 Japanese college students. In our sample, the proportions of women and men with depressive symptoms were 55.28% (95% confidence intervals (CIs) [52.35, 58.20]) and 46.08% (95% CIs [42.63, 49.52]), respectively, using the conventional CES-D cut-off score of 16. A multivariate logistic regression analysis revealed that reassessing coping was significantly associated with a lower risk of depression (OR = 0.92, 95% CIs [0.89, 0.95]), after adjusting for gender. Distancing coping (strategies to actively damage, disrupt, or dissolve a stressful relationship) and constructive coping (strategies to improve, maintain, or sustain a relationship without irritating others) were significantly associated with a greater depression risk. Reassessing coping for interpersonal stressors was associated with a low risk of depression among Japanese college students. PMID- 26155459 TI - Studying antibiotic-membrane interactions via X-ray diffraction and fluorescence microscopy. AB - Antibiotic drug resistance is a serious issue for the treatment of bacterial infection. Understanding the resistance to antibiotics is a key issue for developing new drugs. We used penicillin and sulbactam as model antibiotics to study their interaction with model membranes. Cholesterol was used to target the membrane for comparison with the well-known insertion model. Lamellar X-ray diffraction (LXD) was used to determine membrane thickness using successive drug to-lipid molar ratios. The aspiration method for a single giant unilamellar vesicle (GUV) was used to monitor the kinetic binding process of antibiotic membrane interactions in an aqueous solution. Both penicillin and sulbactam are found positioned outside the model membrane, while cholesterol inserts perpendicularly into the hydrophobic region of the membrane in aqueous solution. This result provides structural insights for understanding the antibiotic membrane interaction and the mechanism of antibiotics. PMID- 26155460 TI - Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice. AB - Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well as prostaglandin E2 production, and also suppressed RANKL expression, which is essential for osteoclast differentiation. LPS-induced bone resorption of mandibular alveolar bones was attenuated by EGCG in vitro, and the loss of mouse alveolar bone mass was inhibited by the catechin in vivo. PMID- 26155461 TI - Stepwise error-prone PCR and DNA shuffling changed the pH activity range and product specificity of the cyclodextrin glucanotransferase from an alkaliphilic Bacillus sp. AB - Cyclodextrin glucanotransferase (EC 2.4.1.19) from the alkaliphilic Bacillus sp. G-825-6 converts starch mainly to gamma-cyclodextrin (CD8). A combination of error-prone PCR and DNA shuffling was used to obtain variants of this enzyme with higher product specificity for CD8 and a broad pH activity range. The variant S54 with seven amino acid substitutions showed a 1.2-fold increase in CD8 synthesizing activity and the product ratio of CD7:CD8 was shifted to 1:7 compared to 1:3 of the wild-type enzyme. Nine amino acid substitutions of the cyclodextrin glucanotransferase were performed to generate the variant S35 active in a pH range 4.0-10.0. Compared to the wild-type enzyme which is inactive below pH 6.0, S35 retained 70% of its CD8-synthesizing activity at pH 4.0. PMID- 26155462 TI - Skin and subcutaneous mycoses in tilapia (Oreochromis niloticus) caused by Fusarium oxysporum in coinfection with Aeromonas hydrophila. AB - Subcutaneous mycoses in freshwater fish are rare infections usually caused by oomycetes of the genus Saprolegnia and some filamentous fungi. To date, Fusarium infections in farmed fish have only been described in marine fish. Here, we report the presence of Fusarium oxysporum in subcutaneous lesions of Nile tilapia (Oreochromis niloticus). Histopathologic evaluation revealed granuloma formation with fungal structures, and the identity of the etiological agent was demonstrated by morphological and molecular analyses. Some of the animals died as a result of systemic coinfection with Aeromonas hydrophila. PMID- 26155463 TI - Morphological and morphometric differentiation of dorsal-spined first stage larvae of lungworms (Nematoda: Protostrongylidae) infecting muskoxen (Ovibos moschatus) in the central Canadian Arctic. AB - Umingmakstrongylus pallikuukensis and Varestrongylus eleguneniensis are the two most common protostrongylid nematodes infecting muskoxen in the North American Arctic and Subarctic. First stage larvae (L1) of these lungworms have considerable morphological similarity that makes their differential diagnosis very difficult. Using light microscopy, we studied in detail the L1 of these two species and identified the key differences in morphological and morphometric attributes. Thirty L1 of each species from naturally infected muskox were heat killed and then assessed for morphological and morphometric features that could be used for species-level differentiation. Key differentiating features include: length and morphology of the tail extension, curvature of the body, ventral post anal transverse cuticular striations, and total body length. A laboratory guide for differentiation of L1 based on these species-specific characters was prepared and used by an experienced observer to identify an additional 35 L1 extracted from a different set of fecal samples from free-ranging muskoxen with mixed infections. The identities of these L1 were confirmed by sequence analysis of the ITS-2 region of the nuclear ribosomal DNA. Accuracy of morphological identification was 100 percent, reflecting the reliability of the proposed guide for differentiation. Using the guide, three minimally trained lab assistants each fixed and accurately identified 10 of 10 randomly selected L1. Ability to morphologically differentiate these facilitates the monitoring of overlapping range expansion of both parasites in the Canadian Arctic. Studies enabling species-level parasite identification are also critical for defining biodiversity, detecting mixed infections, and understanding host-parasite interactions. Morphological identification is a simple, reliable and cost effective alternative to labor and equipment intensive molecular methods and can easily be performed in low resource settings. PMID- 26155464 TI - Sea otter health: Challenging a pet hypothesis. AB - A recent series of studies on tagged sea otters (Enhydra lutris nereis) challenges the hypothesis that sea otters are sentinels of a dirty ocean, in particular, that pet cats are the main source of exposure to Toxoplasma gondii in central California. Counter to expectations, sea otters from unpopulated stretches of coastline are less healthy and more exposed to parasites than city associated otters. Ironically, now it seems that spillover from wildlife, not pets, dominates spatial patterns of disease transmission. PMID- 26155465 TI - Focal frontal epileptiform discharges in a patient with eyelid myoclonia and absence seizures. AB - Eyelid myoclonia with absences is classified as a unique type of generalized seizure. Its pathogenesis is proposed to involve the functional abnormalities in cortical-subcortical networks. Here, we describe the case of a 7-year-old boy who had eyelid myoclonia with absences, along with focal motor seizures. Video-EEG monitoring demonstrated eyelid myoclonia associated with 4- to 5-Hz generalized polyspike-waves preceded by focal frontal discharges. Interictal EEG showed focal epileptiform discharges over the frontal regions. Our case suggests an important role of the frontal lobe in the generation of eyelid myoclonia with absences. PMID- 26155466 TI - Cadaveric Study of Profunda Femoris Artery with Some Unique Variations. AB - BACKGROUND: Profunda femoris artery is the largest branch of femoral artery and chief supply of the thigh. It is useful for various clinical procedures like arteriography, ultrasonography and Doppler imaging and haemodialysis. Hence, accurate anatomical knowledge is very important for the clinicians. MATERIALS AND METHODS: Thirty three properly embalmed cadavers (17 males and 16 females) were selected for the study. Femoral artery, Profunda femoris artery and its branches were exposed and their distances of origin were measured. RESULTS: In present study of profunda femoris artery, we found posterolateral and lateral aspect of origin was common (71.21%) than posterior and posteromedial aspect of origin (24.24%). The site of origin of profunda femoris artery was between 21-40 mm on right side and 11-40 mm on left side. In 14 limbs (21.21%), we found high origin of profunda femoris artery (distance < 10mm). In two limbs (3.03%) Profunda femoris artery was originating from medial side of femoral artery and it coursed superficial to femoral vein. As per various literatures this is rare. In one female cadaver, on left side, we noted high origin (5mm away from mid inguinal point) of profunda femoris artery and site of origin was from anterolateral aspect of femoral artery and all the superficial branches of thigh took origin from it, while on right side of same cadaver findings were normal. In 13 limbs (19.69%) profunda femoris artery took origin as a common stem along with one of circumflex arteries while in three limbs (4.54%) trifurcation was observed, that is origin of profunda femoris and two circumflex arteries from single site. In four limbs (6.06%), superficial branches of femoral artery took origin from profunda femoris artery instead of femoral artery. CONCLUSION: In present study posterolateral and lateral side of origin is noted as common site of origin of profunda femoris artery. Rare variation like medial side origin of profunda Femoris artery was observed and it coursed on femoral vein. Very high incidence of high level of origin of profunda femoris artery was found. In one of the high origin limb profunda femoris artery originated from anterolateral side and all superficial branches of thigh took origin from it. Such variation is unique. Hence, this study will help the clinicians to avoid iatrogenic complications and also help them in various clinical procedures like puncture of femoral artery for interventional radiology. PMID- 26155467 TI - Morphometric Analysis of Axis and Its Clinical Significance -An Anatomical Study of Indian Human Axis Vertebrae. AB - BACKGROUND: The atlas and axis vertebra have unique shape and complex relationship with vertebral artery. Fracture of dens of axis accounts for 7-27% of all cervical spine fractures, but surgeries in these regions are highly risky because of the reported incidences of vertebral artery injury. AIM AND OBJECTIVES: The study was designed to measure morphometric data of human axis vertebra, of Indian origin. The different anatomical parameters on dry specimen of human axis vertebrae were established and the results were compared with other studies. MATERIALS AND METHODS: Thirty intact human axis vertebrae were measured with digital vernier caliper and mini-inclinometer. Various linear and angular parameters of axis were observed. RESULTS: The mean distance from the midline of body to the tip of transverse process of axis was 29.32 mm on right side and 29.06mm on left side. The mean distance from the midline of body to the lateral most edge of superior articulating facet was 22.8 mm on right side and 22.6 mm on left side. The mean value of anterior and posterior height of axis was 34.33+/ 2.69mm and 30.56+/-2.78mm respectively. The anterior and posterior height of body of axis was 19.67 mm and 16.67mm respectively. Mean A-P and transverse diameter of inferior surface of axis was 15.42mm and 17.7mm respectively. Mean transverse diameter and mean A-P diameter of odontoid process was 9.32 mm and 10.1 mm respectively. Mean anterior and posterior height of the odontoid process was 14.66 mm and 13.89mm respectively. Mean of dens axis sagittal angle (angle between an axis that was imagined to pass longitudinally through the dens axis and the vertical line on a sagittal plane) was 13.23 degree. The shape of superior articulating facets of C2 varies from oval to circular. In the present study, 84% of SAF were oval and 16% were circular. Inferior articulating facets were circular in shape in 90% cases, and oval in 10% vertebra. Mean pedicle width was 10.07mm on right side and 10.52mm on left side. Mean transverse diameter of vertebral canal was 22.37+/-1.73mm. Mean of A-P diameter of vertebral canal at inlet was 18.31+/-2.05mm and mean of A-P diameter of vertebral canal at outlet was 14.84+/-1.63mm. CONCLUSION: These results obtained from this study may be helpful for the surgeons in avoiding and minimizing complications such as vertebral artery injury, cranial nerve damage and injury to other vital structures while doing surgery around cranio-vertebral region. PMID- 26155468 TI - Agnathia Holoprosencephaly and Situs Inversus in A Neonate Born to an Alcoholic Mother. AB - Agnathia, holoprosencephaly and situs inversus complex is an extremely rare form of congenital malformation. Though a few cases have been reported from other parts of the world, to the best of our knowledge none has been reported from India so far. Maternal alcoholism is regarded as an important factor causing holoprosencephaly. Disruption of the Shh gene signaling pathway is also said to be a factor for the occurrence of holoprosencephaly as well as left right asymmetry. Though several factors are suspected as a cause of this deformity, the precise aetiopathogenesis is still under debate. Lack of knowledge might be due to paucity of data from cases due to its rarity. Hereby, we are presenting a case of agnathia, holoprosencephaly and situs inversus born at 32 wk of gestation by an alcoholic mother. Externally the child had agnathia and cyclopia. There was no mandible or any oral cavity. It was accompanied by noticeable limb deformity. Internally there was holoprosencephaly, situs inversus totalis with several visceral abnormalities. To the best of our knowledge this is the first case of agnathia, holoprosencephaly and situs inversus complex to be reported in an indexed literature from India. This report also strengthens the association of maternal alcoholism with occurrence of holoprosencephaly. PMID- 26155469 TI - A Bitendinous Palmaris Longus: Aberrant Insertions and Its Clinical Impact - A Case Report. AB - Palmaris longus, phylogenetically a retrogressive muscle, exhibits significant anatomical variations compared to other muscles of the upper extremity. It is of great surgical importance because, it is the first option tendon for graft procedures in various cosmetic, plastic and reconstructive surgeries. It has also been widely used in various tendon transfer procedures in treating facial paralysis, ptosis correction, lip augmentation and digital pulley reconstruction. We report a rare variant pattern of Palmaris longus with duplicated tendons and with multiple insertions to thenar and hypothenar muscles, fasciae and the flexor retinaculum along with its normal continuation as palmar aponeurosis. Variations in its insertions not only contribute, but also augment the various pathological processes such as Dupuytren's contracture, Carpal tunnel and Guyon's syndromes. So it is of utmost importance for surgeons, physicians and radiologists, to be aware of these variations, well in advance. PMID- 26155470 TI - Serological Analysis of Alpha-synuclein and NF-kappaB in Parkinson's Disease Patients. AB - INTRODUCTION: Several investigations have been made to determine the level of alpha-synuclein in the peripheral blood of Parkinson's disease patients, but the results were very contradictory and inconclusive. Nuclear factor kappa-light chain-enhancer of activated B cells (NF-kappaB) was also found to be involved in Parkinson's disease, but there is a lack of studies investigating NF-kappaB in Parkinson's disease patients. As far as our knowledge goes, no study reported the level of NF-kappaB in serum of Parkinson's disease patients. In this context, present study was designed to make a baseline study in order to evaluate the levels of total alpha-synuclein and NF-kappaB in serum of Parkinson's disease patients. MATERIALS AND METHODS: Serum samples were collected from Parkinson's disease patients (n=97) and healthy controls (n=97). Their levels were determined by using Enzyme linked immunosorbent assay. RESULTS: The levels of total alpha synuclein (patients=5.79+/-2.24 ng/ml, controls=6.20+/-1.61 ng/ml; p=0.14) and NF kappaB (patients=1.38+/-0.99 ng/ml, controls=1.65+/-1.00 ng/ml; p=0.71) were lower in Parkinson's disease patients than controls, but the differences were not statistically significant. This difference was also failed to reach significance between males (alpha-synuclein (p)=0.70, NF-kappaB (p)=0.84) and females (alpha synuclein (p)=0.06, NF-kappaB (p)=0.77) in both the groups as well as within the groups. The levels of total alpha-synuclein and NF-kappaB were also not associated with Parkinson's disease severity (alpha-synuclein (p) = 0.84, NF kappaB (p) = 0.73). CONCLUSION: A non-significant difference in the levels of total alpha-synuclein and NF-kappaB between Parkinson's disease patients and controls suggested that these are not valuable biomarkers for Parkinson's disease, more specifically in Indian population. PMID- 26155471 TI - ABER Assessment in Pre-school Children with Developmental Speech and Language Impairment. AB - INTRODUCTION: Developmental speech and language disorders (DLD) constitute a group of disorders when children with normal intelligence and hearing fail to develop language in an age-appropriate manner. There is no definite or surrogate neurophysiologic laboratory marker to quantitate the extent of speech and language impairment. The current study was designed to evaluate the abnormalities in Auditory Brainstem Evoked Responses (ABER) in children with speech and language impairment who do not have a hearing deficit or autism. MATERIALS AND METHODS: ABER recording was done in a cohort of 94 children (age 2-8 y) with DLD without overt hearing deficit or autism. The mean latencies for waves I, II, III, IV and V along with inter peak latencies for I-III, I-V, III-V and amplitude ratio of wave V/I was measured after click stimulus with intensities 110 db until 40 db and compared to age appropriate normograms. RESULTS: The peak latencies for waves I, III & V, inter-peak latencies I-III & I-V, III-V and wave amplitude ratio V/I was found within normal limits in both ears of all the children when compared to age appropriate normograms. CONCLUSION: The current study therefore emphasizes the fact that ABER may not be used/recommended as diagnostic or prognostic tool in children with speech and language impairment without autism or hearing deficit. The results and the recommendations of this study will definitely reduce the burden on electrophysiologist, laboratories and also save time and financial resources. PMID- 26155472 TI - A Study on Prevalence of Phenyl Thiocarbamide (PTC) Taste Blindness Among Obese Individuals. AB - INTRODUCTION: Taste blindness to the phenylthiocarbamide (PTC) is an inherited trait that is shown to influence our food and dietary preferences which in turn influence our body weight. Obesity is a global epidemic issue known to be on rise among the developing countries. Relating taste perception to obesity, the present study was undertaken to assess the prevalence of phenylthiocarbamide (PTC) taste blindness among obese individuals. MATERIALS AND METHODS: Three hundred and fifty individuals of age group 20-40 y were recruited from the local community for the present cross sectional study. Anthropometric measurements were taken and BMI was calculated. Subjects were classified as underweight, normal, overweight and obese based on their BMI. Normal, overweight and obese individuals were then asked to taste the commercially available PTC test papers and classified as non tasters and tasters of PTC. RESULTS: Out of 350 individuals, mean age group of 30+/-6.02 y, based on their BMI they were divided into 4 groups, Group A-underweight (16%), Group B-normal (35%), Group C-overweight (28%) and Group D-obese (21%) individuals. In group B, 28% were non tasters of PTC and 65% were tasters. In group C, 82% were non tasters and 13% were tasters and in Group D, 81% were non tasters and 19% were tasters of PTC. The PTC non taster phenotype individuals showed higher BMI as compared with the tasters' phenotype. CONCLUSION: Exploring the novel connections between taste perception and obesity would help us to gain a control over the global epidemic-Obesity, which is the crux factor for various other health problems. The study advocates the usage of PTC tasting as a reliable indicator of weight gain susceptibility. PMID- 26155473 TI - Effect of Prolonged Use of Mobile Phone on Brainstem Auditory Evoked Potentials. AB - OBJECTIVES: Mobile phones are being widely used throughout the world. Electromagnetic waves generated from mobile phones have raised concerns as these may have adverse effects on human auditory system owing to the daily use of mobile phones. The purpose of current study was to evaluate the effects of long term mobile phone usage on auditory brainstem evoked responses (ABR). MATERIALS AND METHODS: A retrospective, cross-sectional, case control study was carried out in a tertiary care hospital. Total 100 healthy subjects aged 18 to 30 years of both the genders were selected, out of which 67 subjects were long-term GSM mobile phone users (using mobile phone for more than 1 year) and 33 were controls who were mobile phone non users. Both the groups were investigated for ABR and changes were studied in both the ears of cases and controls to ascertain the effects of electromagnetic exposure. RESULTS: No significant difference (p>0.05) was found in latencies, interpeak latencies and amplitudes of ABR waves between cases and controls. CONCLUSION: Our study shows that long term usage of mobile phones does not affect propagation of electrical stimuli along the auditory nerve to auditory brainstem centres. PMID- 26155474 TI - Seroepidemiological Survey of Chikungunya in and Around the Regions of Bijapur (Vijayapura - North Karnataka). AB - BACKGROUND: Chikungunya is a debilitating, non-fatal, mosquito borne viral fever caused by Chikungunya virus (CHIVA). The disease is transmitted to humans by the bite of Aedes aegypti and Aedes albopictus mosquitoes. Severe outbreaks of Chikungunya have been reported in several countries of Africa and Asia. Chikungunya fever is characterized by fever with sudden onset, arthralgia, rash, headache and myalgia. However, arthralgia is painful and long-lasting, affecting primarily the peripheral joints. OBJECTIVES: To find out the prevalence of Chikungunya fever in and around the regions of Bijapur district. MATERIALS AND METHODS: The study was conducted from April 2011 to December 2014. Five hundred serum samples were collected from cases with pyrexia and arthralgia. Serum samples were tested for Chikungunya antibodies by Chikungunya IgM ELISA. RESULTS AND CONCLUSION: Out of 500 samples 33 samples were confirmed positive for Chikungunya IgM antibodies. The prevalence rate of Chikungunya was 6.6% with maximum number of cases in the year 2013 (8.5%) and age group 15 to 40 (8.3%). Females (6.9%) were more affected than males. Thus, continuous sero epidomological surveillance is needed for the control of Chikungunya fever. PMID- 26155475 TI - Rapid Detection of Mycobacterium tuberculosis in Sputum Samples by Cepheid Xpert Assay: A Clinical Study. AB - BACKGROUND AND OBJECTIVE: Tuberculosis (TB) is one of the commonest opportunistic infection and the leading cause of death in HIV patients in developing countries. HIV infection is a well recognised risk factor for both activation of initial infection and reactivation of latent infection. This study was done to find out the co-prevalence and the trend of HIV infection among tuberculosis patients and to determine the prevalence of MDR Tuberculosis in HIV positive patients using Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, United States). MATERIALS AND METHODS: The sputum samples are received from five districts of Punjab. Sputum samples of the patients with symptoms suggestive of pulmonary tuberculosis including both new cases and on treatment are received from the various district and civil hospitals of five districts. Sputum specimen was processed for TB detection by Cartridge Based Nucleic Acid Amplification testing (CB-NAAT) using Xpert MTB/RiF assay technology. RESULTS: The study period is from October 2013 to September 2014. A total of 907 patients with symptoms suggestive of pulmonary tuberculosis including both new cases and on treatment. Out of these patients 733 were reported MTB detected. Out of these 907 patients 29 were reported HIV positive and out of 733 patients 19(2.5%) were reported positive for (HIV +TUBERCULOSIS). Of these 19 cases 16(84.21%) cases were sensitive to rifampicin (RIF) and 3(15.78%) cases were showing resistance to rifampicin (RIF) Drug. CONCLUSION: Co-existence of HIV and tuberculosis is high and there is high Prevalence of MDR tuberculosis in HIV patients. PMID- 26155476 TI - Imaging and Serological-Evidence of Neurocysticercosis Among Patients with Seizures in Odisha, an Unexplored Eastern Coastal Province in India. AB - INTRODUCTION: Neurocysticercosis being a potential to human transmitted disease, is the major cause of seizures and a public health problem in tropical countries. Though India is known to be highly endemic, there are many provinces where reports are still unavailable thereby underestimating its actual burden. MATERIALS AND METHODS: Anti-Cysticercus IgG antibodies in sera from cases presenting with seizures were screened by ELISA in a preliminary study in Odisha state which is a province in Eastern coastal India that was never explored before. Patients presenting with recent onset of seizures within age group 5 to 50 years, either local residents of Odisha or inhabitants from other parts of the country living for at least one year period in the study area were included. RESULTS: The present study showed 43.75% cases with seizures to be confirmed neurocysticercosis (NCC) based on serology and brain imaging. However, statistically no association was established between anti-Cysticercus antibody detection and radio imaging characteristics (location, number of lesions, and stage). CONCLUSION: This is the first study in Odisha presenting a series of cases with serological evidence of exposure to the parasite along with imaging characteristics which was consistent with NCC. It is recommended that NCC must be considered for a differential diagnosis in each active epilepsy case irrespective of prior prevalence information in all unexplored provinces in India and other endemic regions; also a compulsory reporting is warranted in order to aid in quantifying its actual burden. PMID- 26155477 TI - Prevalence of Enterotoxin Genes and spa Genotypes of Methicillin-resistant Staphylococcus aureus from a Tertiary Care Hospital in China. AB - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes a variety of infections. MRSA has evolved resistance to multiple antibiotics. Genetic background and virulence differs in different geographic regions. The present study was aimed to investigate the prevalence of enterotoxin genes and spa genotypes of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) isolated from a tertiary care hospital of Jiangsu province, China. MATERIALS AND METHODS: HA-MRSA isolates from August 2013 to April 2014 at a tertiary care hospital of China were collected. We investigated antimicrobial pattern, spa types, SCCmec types and the presence of 14 virulence genes. RESULTS: Eighty HA-MRSA isolates were collected. Results from SCCmec typing revealed that 73.8% were type II; 13.8% were type III; 12.5% were type V. There were 19 different spa types. Spa type t2460 was the most common (35.0%), followed by t002 (11.3%). CC5 was the predominant MLST CCs type (50%). The most frequent toxin genes were sea, seb, sed, sel, sen and seo (100.0%). None of the investigated isolates carried the sec or tst. CONCLUSION: Genotypic and virulence evaluation of the isolated HA-MRSA revealed that the isolates with CC5 and SCCmec II were the predominant type and highly homological. The virulence profiles mainly existed in the genes of sea, seb, sed, sel, sen, seo and ser. The prevalence of t2460 was an outbreak and the predominant spa type. PMID- 26155478 TI - Correlation Study Between HCV Genotypes Distribution Pattern and Viral Load in a Tertiary Care Hospital in Kolkata, India. AB - BACKGROUND: Hepatitis C virus infection is a leading cause for chronic liver disease. It has wide population specific genotype variability. Genotype knowledge and viral load assessment are equally important for designing therapeutic strategies and as predictors of treatment outcome among hepatitis C (HCV) infected patients. MATERIALS AND METHODS: Between June 2012 and 2013 an observational study was conducted among 350 chronic hepatitis patients visiting Calcutta National Medical College, Kolkata, India. Among them, 110 anti-HCV antibody positive cases were diagnosed and subjected to viral RNA extraction, viral genotyping and viral load quantification using polymerase chain reaction (PCR) based techniques. STATISTICAL ANALYSIS: Statistical analysis was done with IBM SPSS Statistics software, version 20. p-value <0.05 was regarded as statically significant. RESULTS: Among 66 HCV RNA positive cases, genotypes 1a, 3a and 3b were observed among 18 (27%), 44(67%) and 4(6%) cases respectively. Genotype 3a had higher viral load than patients infected with genotypes 1and 3b. However, no statistical significance was observed for viral load among the various HCV RNA genotypes. CONCLUSION: Genotype 3a accounted for the highest number of cases with positive HCV RNA. However, no statistically significant difference existed for viral load among the various HCV RNA genotypes in this study. PMID- 26155479 TI - Association between Experimental Bacterial Meningitis and Periapical Lesion. AB - INTRODUCTION: Mortality and morbidity from bacterial meningitis in African adults is significantly higher than those in better resourced settings. At the same time, the periodontal diseases are highly prevalent and can affect up to 90% of the population. Dental caries in Uganda was recorded in 40% and 62.5% of the children and adults, respectively. We hypothesize that pneumococcal meningitis could interfere in the development of periapical lesion. The aim of this study was to evaluate periapical lesion in Wistar rats subjected to pneumococcal meningitis. MATERIALS AND METHODS: The animals were divided in control, control/periapical lesion, meningitis, and meningitis/periapical lesion groups. The surgical exposure of molars and the infection of the dental pulp were from the oral environment. Pulp necrosis was induced on the left mandibular first molars during adulthood. Dental pulps were exposed by drilling cavities on the central portion of the occlusal surface with a 1011 HL round bur in high speed to a depth nearly equal to the bur diameter. Animals were subjected to behavioral task and evaluation of the size of periodontal ligament. Data from periodontal ligament space and open field task were reported as mean +/- SEM and analysed by Two-way ANOVA and paired Student's t-test, respectively. RESULTS AND CONCLUSION: Meningitis/periapical increased the periodontal ligament space by 61% when compared with control/periapical. In the open-field task, there were no differences in the number of crossings and rearing movements between training and test session in meningitis and periapical lesion groups demonstrating habituation memory impairment. Bacterial meningitis and periapical lesion may play an important role in development of cognitive impairment. PMID- 26155480 TI - Abdominal Tuberculosis: A Diagnostic Dilemma. AB - BACKGROUND: Abdominal tuberculosis (TB) is the sixth most common form of extra pulmonary site of infection after lymphatic, genitourinary, bone and joint, miliary and meningeal TB with a rising incidence in recent years. TB can affect any part of the gastro-intestinal (GI) tract including anus, peritoneum and hepato-biliary system. The clinical manifestations of abdominal tuberculosis are non-specific and mimic various GI disorders and cause delay in diagnosis and management. AIM: To evaluate the various clinical, radiological and microbiological findings of abdominal tuberculosis and to define the role of histopathological examination in establishing the diagnosis in resource poor settings and to analyze the compliance and response to anti-tubercular treatment. MATERIALS AND METHODS: A five year retrospective study (January 2010 to December 2014) was done in a tertiary teaching hospital in Northern India and all the cases diagnosed as abdominal tuberculosis during the study period, were included. The relevant clinical informations, laboratory results, microbiological and radiological investigations were recorded. Histopathological examination of all the resected / excised specimens was done and Ziehl-Neelsen (ZN) staining to detect the tubercular bacilli and Periodic acid-Schiff (PAS) stain to rule out fungal infection was done in all the cases. RESULTS: Out of 48 cases with abdominal tuberculosis, the average age of presentation was 27.4 years with a slight male predominance (Male:Female=1.4:1). Abdominal pain (100%) was the most common presenting symptom followed by anorexia (98%), fever (88%) and intestinal obstruction (88%). The ileum was the most common site of involvement. All the 45 resected / excised tissue specimens (34 cases of intestinal resection and 11 cases of intesinal, omental and lymph nodes biopsies) showed epithelioid granulomas along with necrosis (in 38 cases) and Langhans giant cells (in 42 cases). Acid Fast Bacilli (AFB) positivity was seen in 5 tissue specimens only. All patients were put on anti-tubercular treatment and majority showed good response to therapy. CONCLUSION: Abdominal tuberculosis should be considered as a differential diagnosis in patients with vague GI symptoms. Study of histopathological findings can aid in the diagnosis in the settings where advanced molecular methods of diagnosis are not available, leading to early diagnosis and management. PMID- 26155481 TI - Primary Small Cell Carcinoma of The Esophagus - An Eight Year Retrospective Study. AB - INTRODUCTION: Primary small cell carcinoma of the esophagus is a rare and aggressive tumor. Patients present with metastatic disease and have a poor clinical outcome. The objective of the study was to correlate clinical and histopathological features of primary small cell carcinoma of the esophagus diagnosed and treated at our hospital. MATERIALS AND METHODS: A retrospective study of 11 patients diagnosed with primary small cell carcinoma of the esophagus in Kasturba Hospital, Manipal between 2006 and 2014 was done. The histopathological and immunohistochemical features were correlated with clinical and endoscopic findings. RESULTS: Eleven patients were diagnosed to have small cell carcinoma of esophagus with a male preponderance. Common presenting symptoms were dysphagia and weight loss. Majority of the patients showed mid esophageal ulceroproliferative growth. Biopsy findings were consistent with the characteristic morphology of small cell carcinoma and demonstrated immunoreactivity to neuroendocrine markers. In addition, few cases also showed adjacent squamous dysplasia/carcinoma. Most of the patients presented with metastatic disease, liver being the most common site. These patients were treated by chemotherapy and radiotherapy. CONCLUSION: Esophageal small cell carcinomas are aggressive tumors with high rates of distant metastasis. Presence of squamous dysplasia /squamous cell carcinoma in the adjacent mucosa supports the hypothesis that this neoplasm arise from pleuripotent stem cells. Presence of the latter is also useful to rule out spread from lung primary. PMID- 26155482 TI - Lymphangiomatous Polyp of Palatine Tonsil in A Child Presenting with Dysphagia and Dysarthria. AB - Pedunculated lymphangiomatous polyps of the tonsil are rare benign lesions that have been described in literature using varied nomenclature. Majority of the cases have been reported in adults with varying clinical symptoms. We report a case of lymphangiomatous polyp of left palatine tonsil in a 14-year-old male child who presented with dysphagia and dysarthria. Clinical examination revealed a large pedunculated polyp arising from upper pole of left tonsil. Patient underwent left tonsillectomy with excision of the polyp. Based on histopathological features a diagnosis of pedunculated lymphangiomatous polyp was made. We discuss the clinical and histopathological features of this lesion with differential diagnosis and short review of literature. PMID- 26155483 TI - Disseminated Congenital Neuroblastoma - An Autopsy Case Report. AB - Neuroblastoma is the most common malignant tumour in the neonatal age group. The tumour is derived from neural crest cells of adrenal gland medulla or sympathetic ganglia. Disseminated congenital neuroblastoma is very rare. We hereby report a case of congenital neuroblastoma with multiple metastases diagnosed on autopsy in a fetus of 23 weeks gestational age. Autopsy revealed enlarged bilateral adrenals, large fusiform mass in the right humerus, mass in the lower lobe of left lung and posterior chest wall. Diagnosis of disseminated congenital neuroblastoma was given after histopathological and immunohistochemical examination. We are reporting this case for its rare presentation of disseminated form of congenital neuroblastoma sparing liver. PMID- 26155484 TI - Signet Ring Dermatofibroma, a Rare and Confusing Variant. AB - Dermatofibroma is a common cutaneous benign fibrohistiocytic tumour, which is usually diagnosed without difficulty. In this report we demonstrated a signet ring variant of dermatofibroma as a rare variant of this common neoplasm together with the possible differential diagnosis.The presence of signet cells in cutaneous neoplasm does not necessarily means malignancy. Signet ring dermatofibroma is a rare variant eliciting differential diagnostic problems which can be solved by careful histopathological examination, searching for the classic areas and the help of immunohistochemistry. PMID- 26155485 TI - Extraskeletal Chondroma of the Gluteal Region Along with Sporadic Neurofibroma - An Unusual Presentation. AB - Extraskeletal or soft tissue chondroma is a benign cartilaginous tumour that predominantly involves the hands and feet. We present a rare case of gluteal extraskeletal chondroma in a 55-year-old Indian female. She presented with right gluteal mass measuring 5 cm in greatest dimension. The diagnosis was provided through histopathological examination of completely excised tumour mass. The patient also had sporadic neurofibroma in the supraclavicular region. Such a unique association has not been reported till date in the English literature. We describe the clinical and histopathological characteristics of our case, emphasizing the first reported association of extraskeletal chondroma and sporadic neurofibroma. PMID- 26155486 TI - Choroid Melanoma - A Rare Case Report. AB - Uveal tract encomprise melanomas of the iris, ciliary body and the choroid. The choroid melanomas are more frequent to occur in comparison to iris and ciliary body melanomas. Choroid melanoma though rare, is the most common occurring intraocular malignancy amongst the adults. Incidence of occurrence of choroid melanoma is around 20 per million cases per year globally. The uveal tract pigment producing melanocytes are the origin for the melanoma in the eye. Melanomas tend to commonly arise from sixth decade of age with increasing incidence with progressive age. We present a rare case choroidal melanoma, in a 65-year-old adult, who presented with three months history of headache and gradual dimunision of vision, his investigations revealed clinical diagnosis of choroid melanoma , an enucleation was carried. PMID- 26155487 TI - Foray of Cytologically Diagnosed Intramuscular Sarcocystosis- A Rarity. AB - Sarcocystosis is an uncommonly encountered zoonotic coccidial protozoal infestation of human beings. The sarcocystis species is known to produce intestinal and muscular infestations in humans. We report a rare case of a 35 year-old female with an intramuscular swelling in the lumbar region diagnosed cytologically as "Intramuscular Sarcocystosis" and subsequently confirmed on histopathology. This case highlights the role of fine needle aspiration cytology in the identification of Sarcocystis and its role in differentiating it from other intramuscular parasites which is of immense value in precise diagnosis and appropriate patient management. PMID- 26155488 TI - Metastatic Small Cell Carcinoma of Lung To Pancreas Mimicking As Acute Pancreatitis: A Case Report. AB - Small cell carcinoma (SCC) of lung is a highly malignant tumour and is notorious for early and widespread metastasis at the time of presentation. However, metastasis to pancreas occurs uncommonly. Metastatic lesions comprise of 3% of all pancreatic malignancies. We hereby present a rare case report where patient presented with symptoms of acute pancreatitis & diagnosed with SCC of lung, retrospectively. This case emphasize that acute pancreatitis can be a manifestation of malignancy and fine needle aspiration cytology can play a diagnostic role in such cases. PMID- 26155489 TI - Evaluation of the Analgesic Activity of Standardized Aqueous Extract of Terminalia chebula in Healthy Human Participants Using Hot Air Pain Model. AB - BACKGROUND: Pain affects millions of people worldwide, opioid analgesics have been used for chronic painful conditions. Due to their adverse effects, safer alternatives would be beneficial. Terminalia chebula, with proven analgesic action has been evaluated in the hot air pain model for its analgesic activity. AIM: To evaluate analgesic activity and safety of single oral dose of Terminalia chebula using hot air pain model in healthy human participants. SETTING AND DESIGN: Randomized, Double blind, Placebo controlled, Cross over study. MATERIALS AND METHODS: After taking written informed consent to IEC approved protocol, 12 healthy human participants were randomized to receive either single oral dose of two capsules of Terminalia chebula 500 mg each or identical placebo capsules in a double blinded manner. Thermal pain was assessed using hot air analgesiometer, to deliver thermal pain stimulus. Mean Pain Threshold time and Mean Pain Tolerance time measured in seconds at baseline and 180 minutes post drug. A washout period of two weeks was given for cross-over between the two treatments. RESULTS: Terminalia chebula significantly increased mean pain threshold and tolerance time compared to baseline and placebo. Mean pain threshold time increased from 34.06+/ 2.63 seconds to 41.00+/-2.99 seconds (p<0.001) and mean pain tolerance time increased from 49.67+/- 3.72 seconds to 57.30+/-3.07 seconds (p<0.001). The increase in mean percentage change for pain threshold time is 20.42% (p<0.001) and for pain tolerance time is 17.50% (p<0.001). CONCLUSION: In the present study, Terminalia chebula significantly increased Pain Threshold time and Pain Tolerance time compared to Placebo. Study medications were well tolerated. PMID- 26155490 TI - Cost Analysis of Commonly used Combination of Drugs in Primary Open Angle Glaucoma. AB - BACKGROUND: Glaucoma is second cause of blindness in the world. The financial burden on the patient during long-term treatment is immense and affects the compliance to medications, thus visual morbidity. OBJECTIVE: To analyse economic impact of three commonly used drug combinations (Dorzolamide + Timolol = DT; Brimonidine + Timolol = BT; Latanoprost+Timolol = LT) in primary open angle glaucoma. MATERIALS AND METHODS: This observational, prospective study was undertaken at M & J Institute of Ophthalmology, Civil Hospital, Ahmedabad, a western regional institute of Ophthalmology. A total of 257 patients were included in the study. Only101 patients could complete the 6 month follow-up, of which 35, 34 and 32 patients belonged to DT, BT and LT group respectively. Cost of drug, details of the transportation were noted at every visit. Total cost incurred per patient/eye was calculated. Cost effectiveness was calculated by cost per mm Hg IOP (Intra-Ocular Pressure) reduction. RESULTS: Treatment with DT, BT & LT group consumed 8.6%, 4.6% and 7.7% of the per annum income of the family, respectively. Cost of medications per annum (in INR)/eye for DT, BT & LT group were 2562 +/- 15.74, 1544 +/- 32.06, 3876 +/- 73.68 (Mean+/-SEM) respectively. Additional cost of travelling was different for patients coming from Ahmedabad (Locals) and outsiders (patients coming outside Ahmedabad, India). Outsiders has to bear the brunt of higher transport charges, where they spent an average of Rs. 914, 856 & 933 per annum (5 follow-ups), whereas, Locals spent an average of Rs. 104, 112, 100 for DT, BT & LT group respectively. CONCLUSION: Treatment with BT was found to be most cost-effective among three groups. Drug therapy takes substantial amount from per annum income of family and was an important compliance factor in the treatment of POAG. PMID- 26155491 TI - Multiple Adverse Effects of Systemic Corticosteroids: A Case Report. AB - Corticosteroids are among the effective treatments available for many medical conditions. Adverse effects such as osteoporosis, cataract and muscle weakness are widely recognized on long term administration and have considerable public health implications. Many reports are available that have dealt with individual adverse effects.Here, we report a case of a 55-year-old female, with systemic glucocorticoid induced bilateral cataract, osteoporosis, diabetes mellitus and hypothalamic pituitary axis (HPA) suppression. These were induced through self medication. She presented to the hospital for the treatment of acute exacerbation of bronchial asthma. PMID- 26155492 TI - Antioxidant Activity and Teratogenicity Evaluation of Lawsonia Inermis in BALB/c Mice. AB - BACKGROUND AND AIM: Lawsonia inermis is a medicinal plant with abortive properties. There has been no scientific study to evaluate the teratogenicity of this plant. This study was performed to determine the antioxidant activity and the possible side effect of L. inermis hydroalcoholic extract on development of congenital abnormalities in BALB/c mice. MATERIALS AND METHODS: In this experimental study, 120 female mature BALB/c mice were assigned to four groups and after mating and confirming the vaginal plug, the animals in the first group (G1) were kept with no intervention, and the second (G2), third (G3) and fourth (G4) groups were intraperitoneally (ip) injected with respectively saline (0.3 ml), and 10 and 100 mg/kg of L. inermis extract (for 7 days). On the 19th day, caesarean section was performed on the mice and embryos were examined for abnormalities. Their height and weight were measured. Data were analysed by ANOVA and post-hoc least significant difference tests. RESULTS: There were significant differences between G3 and G4, and G1 (p<0.001); no significant difference was seen between G3 and G4. At 100 mg/kg dose of L. inermis, the parietal bones were absent in 90% of embryos and more extra ribs were observed in both G3 and G4 (p = 0.01). CONCLUSION: L. inermis may have teratogenicity and should be used cautiously during pregnancy. PMID- 26155493 TI - Anti-Inflammatory Effect of Selected Dihydroxyflavones. AB - BACKGROUND: The mechanism of inflammation is attributed, to release of reactive oxygen species from activated neutrophils and macrophages. Over production of reactive oxygen species may result in tissue injury by damaging macromolecules. Flavones are the polyphenolic compounds with antioxidant property. This antioxidant property of flavones may have beneficial effect against inflammation. AIM: To study the anti-inflammatory effect of selected dihydroxyflavones (DHF) in albino rats. The prime objective of the present study is to identify safe and effective agents to treat inflammation from among the selected DHF group of compounds. MATERIALS AND METHODS: The present study was designed to investigate the anti-inflammatory action of four selected dihydroxyflavone derivatives; 2',3' dihydroxyflavone and 2', 4' -dihydroxyflavones, 5, 3'- dihydroxyflavone and 7, 3' dihydroxyflavone. The anti-inflammatory activity of selected DHF was studied in rats by carrageenan induced hind paw oedema method. RESULTS: All the selected dihydroxyflavone derivatives showed dose and time dependent inhibition of carrageenan induced paw oedema. PMID- 26155494 TI - Dose Dependent Hepatic and Endothelial Changes in Rats Treated with Dexamethasone. AB - AIMS AND OBJECTIVES: To study the effect of dexamethasone on liver and endothelium, and to determine the optimum dose which induces the abnormal changes in liver and endothelium in Wistar rats. MATERIALS AND METHODS: Albino Wistar rats were divided into 7 groups (n=6). Control group rats received normal saline. Graded doses of dexamethasone (0.5,1,2,4,8 and 16mg/kg/ i.p.) was administered to the groups for six days. Liver and aorta were dissected at the end of the study and examined for histopathological changes under microscope. RESULTS: Intraperitoneal administration of dexamethasone (4,8 and 16mg/kg) for six days resulted in fatty changes in liver and same doses have shown thickening of endothelial layers in aorta, in comparison to control group. There were not much significant changes seen in low doses of dexamethasone (0.5, 1 and 2mg/kg). CONCLUSION: It is concluded that the acute high doses of dexamethasone (4,8 and 16mg/kg) for six days caused hepatic steatosis and showed mild to moderate arteriosclerosis in aorta. These changes may be secondary consequences of insulin resistance. Hence, it can be used as new animal model to screen the various plants and medicines in the treatment of insulin resistance. PMID- 26155495 TI - Effect of Gabapentin and Pregabalin in Rat Model of Taxol Induced Neuropathic Pain. AB - BACKGROUND: Chemotherapy induced neuropathy pain remains as a major dose limiting side effect of many commonly used chemotherapeutic drugs. Presently newer antiepileptic agents have been developed with improved safety and tolerability profiles in alleviating neuropathic pain. OBJECTIVES: To evaluate the effect of Gabapentin and Pregabalin in Paclitaxel (Taxol) induced neuropathic pain and to compare the effect of these drugs in animal models. MATERIALS AND METHODS: Rats were randomly divided into four groups of six animals each. Group 1- vehicle, Group 2 - Paclitaxel (2mg/kg), Group 3 - Gabapentin (60mg/kg) with Paclitaxel, Group 4 - Pregabalin (30mg/kg) with Paclitaxel. Pain was induced by intraperitoneal injection of Paclitaxel on four alternate days. After taking the baseline values, the drugs treated groups (group 3 and 4) were administered with respective drugs once a day orally for eight consecutive days along with paclitaxel. All the animals were tested for thermal hyperalgesia and cold allodynia on day 0, 7, 14, 21 and 28 with Radiant heat method and Tail immersion test, Acetone drop method respectively. RESULTS: In Radiant heat method, gabapentin and pregabalin treated animals found to have significant increase in the tail latency period compared to control and paclitaxel treated groups in all periods of observation. Acetone drop test and tail immersion test also showed significant response similar to Radiant heat method. Pregabalin showed highly significant effect when compared to gabapentin group. CONCLUSION: Both gabapentin and pregabalin produced significant anti-hyperalgesic and anti-allodynic effects in experimental animal models. Pregabalin treated group showed highly significant effect compared to gabapentin treated animals. PMID- 26155496 TI - Publishing Case Reports and Case Series in Indian Biomedical Journals - Ethical Issue Often Neglected. PMID- 26155497 TI - Types, Risk Factors, Clinical symptoms and Diagnostic Tests of Acute Adult Meningitis in Northern Iran During 2006-2012. AB - BACKGROUND: Acute bacterial meningitis is a medical emergency condition that requires prompt diagnosis and treatment and otherwise associated with serious morbidity and mortality. AIM: The aim of this study was to assess types, risk factors, clinical symptoms and diagnostic tests of meningitis in hospitalized patients of Mazandaran University of medical sciences hospitals during 2006-2012. MATHERIALS AND METHODS: This is a retrospective descriptive study. Following approval of the ethics committee of Mazandaran University of Medical Sciences, records of adult patients diagnosed with acute meningitis from 2006 to 2012 were extracted from Mazandaran Provincial Health Center and patients attending hospitals affiliated to Mazandaran University of Medical Sciences. STATISTICAL ANALYSIS: Data were analyzed with SPSS-16 using descriptive statistics (frequency, mean, standard deviation, and median). RESULTS: In this study, of the 137 patients with meningitis, 73 (53.9%) were viral, 61 (46%) bacterial, 1 (0.7%) fungal, and 2 (1.4%) unknown. The majority of risk factors in patients were head trauma, upper respiratory infection, and drug addiction. The most common clinical signs were headache, fever, nausea and vomiting, and stiff neck. CONCLUSION: In this study, the incidence of meningitis was much lower than any other country. It could be due to geographic variation or incomplete recording of patient's data. It is recommended to perform a longitudinal study during the coming years on patients with meningitis. PMID- 26155498 TI - Prevalence of Intestinal Parasitic Infection Among Inhabitants and Tribes of Chelgerd, Iran, 2008-2009. AB - INTRODUCTION: Although a notable development in treating and controlling of parasitic infections in recent years has occurred but, these infections are still counted as important problems in many countries. AIM: The aim of this study is to determine the prevalence of intestinal parasitic infections in the inhabitant and tribe populations who were referred to central health care of Chelgerd, Iran. MATERIALS AND METHODS: This descriptive cross-sectional study was carried out from April 2008 to October 2009 in Chelgerd, Iran. A total of 655 samples of feces from inhabitants and tribes were collected and each sample was examined by Direct smear, formol- ethyl acetate concentration and Trichorom staining. RESULTS: Out of 655 stool samples, 367(56%) patients revealed at least one intestinal parasite (pathogenic /non-pathogenic protozoa/helminth), 233(67.7%) in tribes and 134(43%) in inhabitants. There was significant difference between infected inhabitants and infected tribes (p=0.001). Although the intestinal parasitic infections were more in female than male it was not statistically significant (p=0.52). There was no significant difference in various age groups. Common intestinal parasitic infections which were detected in both the populations were Giardia intestinalis (28.2%) and Blastocystis hominis (27.5%). CONCLUSIONS: We found that the prevalence of intestinal parasitic infections was higher in the tribe than inhabitant populations. Prevalence of intestinal protozoa infections was much higher than the helminthic infections. These findings reflect poor sanitary conditions in this region. They should be educated and provided better facilities to get rid of intestinal parasitic infections. PMID- 26155499 TI - Concentration of Fluoride in Cow's and Buffalo's Milk in Relation to Varying Levels of Fluoride Concentration in Drinking Water of Mathura City in India- A Pilot Study. AB - AIM: To estimate fluoride concentration in drinking water, cow's milk and buffalo's milk and to correlate the concentration of fluoride in cow's milk and buffalo's milk with varying levels of fluoride concentration in drinking water. MATERIALS AND METHODS: Ten households having both cows and buffalo's were selected by convenience in each of the 3 zones (below optimum fluoride <0.7 ppm (parts per million), optimum fluoride 0.7-1.2 ppm and above optimum fluoride areas > 1.2 ppm). From these selected households, 200 ml of fresh milk of both cows and buffaloes was collected along with 200 ml of drinking water for estimation of fluoride concentration by using a fluoride ion selective electrode method. The data was analysed using SPSS, version 11.5 for windows. RESULTS: The mean fluoride concentration of drinking water, cow's milk and buffalo's milk in three different fluoride zones was 0.89+/-0.39, 0.09+/-0.07, 0.09+/-0.08 respectively. Pearson's correlation found a statistically significant correlation between fluoride concentrations in cow's and buffalo's milk with varying levels of fluoride concentration in drinking water in zone B and zone C. However, this correlation was not statistically significant in zone A. CONCLUSION: With an increase in fluoride concentration in drinking water there was an increase in concentration of fluoride in cow's and buffalo's milk. We conclude that this association is seen in conjunction to not only a single factor but rather due to culmination of several other aspects. So, there is a need to elucidate the other factors that might be contributing to this increase and dental fluorosis. PMID- 26155500 TI - Exploring Factors that Influence Smoking Initiation and Cessation among Current Smokers. AB - INTRODUCTION: Worldwide, cigarette smoking kills 5 million people annually, and leads to illness, disability and death. This study aimed to assess the factors influencing smoking initiation and cessation among current smokers in Chennai, India. MATERIALS AND METHODS: This cross-sectional study was conducted in September 2013 in Chennai, India. A convenient sample of 100 current smokers aged >15 years was enrolled. A modified version of Alcohol, Smoking and Substance Involvement Screen Test (ASSIST) questionnaire was used to gather information on socio-demographics, smoking initiation and cessation, expenditure on smoking products and perceptions on incentives for smoking cessation. RESULTS: Surrounding influence (44%), stress (42%) and fun (40%) were major reasons for smoking initiation. Majority of participants (68%) attempted to quit smoking within past 6 months but failed. Health promotion programs (61%) and financial incentives (20%) were perceived to be helpful in smoking cessation. CONCLUSION: Smoking cessation strategies, especially at workplaces, should target the multi factorial nature of smoking initiation and cessation. There is a need to review national guidelines to evaluate the accessibility and availability of smoking products in and around the workplace. PMID- 26155501 TI - Fast Food Consumption Pattern and Its Association with Overweight Among High School Boys in Mangalore City of Southern India. AB - CONTEXT: Fast foods are quite popular among children owing to taste, appearance and hype created by mass media. However, the increased incidence of lifestyle disorders seen now-a-days at an early age could be attributed to fast foods. AIM: This study was done to assess the awareness of health hazards, consumption pattern of fast foods and to find out its association with overweight among high school students. SETTINGS AND DESIGN: This cross-sectional study was done among boys of 3 private schools in Mangalore city in March 2012. MATERIALS AND METHODS: Data was collected using a semi-structured self-administered questionnaire. STATISTICAL ANALYSIS: Chi-square test, one-way ANOVA and binary logistic regression analysis was used for analysis. P-value <= 0.05 was considered as statistically significant association. RESULTS: Mean age of boys was 13.5+/-0.9 years. Out of 300 participants, 41(13.7%) were overweight and 8 (2.7%) were obese. 292(97.3%) were fast food users of which 42(14.4%) consumed it every day. Majority of participants were introduced to fast foods through television commercials 193(64.3%). 73(57%) developed this habit as they were bored with home food. Awareness of harmful effects of fast food consumption was known to 186(62%) students and this was found to be associated with the perceived need to control its usage (p<0.001). Parental consumption of fast foods was found to influence fast food consumption among children (p=0.024). As many as 68(22.7%) and 206(68.7%) children were not eating vegetables and fruits respectively every day. Increased frequency of fast food consumption in a week was found to be associated with overweight or obesity among children after adjusting the effects of confounders (p=0.003). CONCLUSION: Awareness on health hazards of fast foods needs to be taught at schools so as to minimize its consumption. Parents have to set an example themselves by not eating fast foods and improving home food to support discouragement of fast foods. This would minimize life style disorders among children to a greater extent. PMID- 26155502 TI - Impact of Health Education on The Knowledge, Attitude and Practices of Teachers Regarding Reproductive Health of Adolescents of Amritsar, Punjab. AB - CONTEXT: Teachers play an important role in guiding the adolescents. Adolescents are ill equipped to deal with the impending changes in their body which makes them vulnerable to STDs, HIV/AIDS and premarital sex. This study attempts to study the impact of reproductive health education on the knowledge, attitude and practices of teachers, about which only a few studies are available. AIMS: To study the impact of health education on the knowledge, attitude and practices of teachers regarding reproductive health of adolescents. SETTINGS: Senior Secondary schools of Amritsar and Department of Community Medicine, Government Medical College, Amritsar, Punjab, India. STUDY PARTICIPANTS: Male teachers of senior secondary schools of Amritsar teaching class 9th-12th. STUDY DESIGN: Educational intervention study. SAMPLING METHOD: Purposive sampling. MATERIALS AND METHODS: The study was started with 155 teachers (teaching class 9th -12th) who willingly participated from 50 senior secondary schools of Amritsar district. It was carried out in three phases. In first phase, after taking informed consent, the teachers filled a pretested questionnaire which was followed by an interactive session on reproductive health in second phase. In third phase, to study the impact of the interactive session and the sustainability of knowledge gained, they were again administered the same questionnaire after a period of 3 months. STATISTICAL ANALYSIS: Microsoft Excel, SPSS, Chi-square test. RESULTS: Maximum 74 (47.7%) teachers were aware of the psychosocial problems of adolescents. Majority 110 (71%) of the teachers had only partial knowledge about pubertal changes. 117 (75.5%) teachers were unaware about genital hygiene. Only 33 (21.3%) teachers had adequate knowledge about different STDs. 91 (58.7%) and 54 (34.8%) of teachers had adequate knowledge about routes of transmission and prevention of AIDS respectively. Only 37 (23.9%) teachers were imparting sex education to students. After intervention significant favorable changes were seen in their knowledge, attitude and practices regarding most of above mentioned topics. CONCLUSION: Although the baseline knowledge of teachers in most aspects of reproductive health of adolescents was found to be low, significant favourable changes were observed after health education. PMID- 26155503 TI - Rhinosporidiosis: A Chronic Tropical Disease in Lateral Pharyngeal Wall. AB - Rhinosporidiosis is a chronic granulomatous disease caused by Rhinosporidium seeberi. It predominantly affects the mucous membranes of the nose and the nasopharynx. Clinically the lesion presents as a pink or red pedunculated polyp in one or both nostrils. Diagnosis can be made by aspiration cytology and examination with May-Grunwald-Giemsa, hematoxylin and eosin, Periodic acid-Schiff and mucicarmine staining. Definitive diagnosis is by histopathology of the specimen. We report a case of Rhinosporidiosis at the lateral pharyngeal wall which is a very rare site for Rhinosporidiosis to occur; was treated by diathermy excision of the mass and cauterization of the base and oral Dapsone to prevent recurrence of the disease. PMID- 26155504 TI - Comparative Analysis of Clinical Factors Associated with Ocular Surface Squamous Neoplasia in HIV Infected and Non HIV Patients. AB - INTRODUCTION: Ocular surface squamous neoplasia (OSSN) refers to a spectrum of conjunctival and corneal epithelial disease ranging from dysplasia to invasive carcinoma. HIV infection is an important risk factor postulated for the development of disease. AIM: To compare and to find out any statistically significant difference in patient demographics, clinical features and pathological findings in HIV infected and non-HIV infected histologically proven cases of ocular surface squamous neoplasia (OSSN). MATERIALS AND METHODS: In the present retrospective case study, data from indoor case records and ocular pathology records of histologically proven cases of OSSN was obtained. The data was then tabulated under various clinicopathological headings in HIV affected and non HIV affected groups. A chi-square test was applied to compare data of two groups and look for any significant difference between two groups. A p-value less than 0.05 was considered significant. RESULTS: Amongst the total of 48 patients, 11 were HIV positive and 37 were HIV negative. Age of the patients ranged from 14 66 years in HIV and 22-66 years in non HIV group with a preponderance of younger age patients in HIV positive group. 54.5% patients with lesion having base more than 5mm were observed at the time of presentation in HIV positive population as compared to 21.6% in non HIV cases. Feeder vessels were seen in all HIV patients and a significantly greater degree of fornicial involvement was noted in comparison with non-HIV group. Histopathological analysis showed 63.63% of cases to be of invasive carcinoma amongst the HIV positive group and 54.05% of invasive carcinoma in non HIV group. CONCLUSION: Younger age and aggressive looking tumour at presentation should caution ophthalmologist to look for an undiagnosed HIV infection in OSSN patients. PMID- 26155505 TI - Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report. AB - Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy. PMID- 26155506 TI - Effectiveness of Insulin Glargine on Recovery of Patients with Diabetic Ketoacidosis: A Randomized Controlled Trial. AB - BACKGROUND: Diabetic Ketoacidosis (DKA) is a major hyperglycemic emergency in diabetes mellitus (DM). The basic treatment is injection of Regular insulin (RI). This study was aimed to investigate the effects of insulin Glargine (GI) on recovery of patients with DKA. MATERIALS AND METHODS: A randomized clinical trial conducted on 40 patients (twenty patients in each group) with DKA. Both groups received standard treatment for DKA. Experimental group was given 0.4U/kg of GI within three hours of initiation of IV insulin infusion. RESULTS: The mean duration of acidosis correction time and recovery from DKA was 13.77+/-6.10 and 16.91+/-6.49 h in the intervention and control groups respectively (p=0.123). The mean dosage of RI until recovery from DKA was 84.8+/-45.6 in the intervention and 116.5+/-91.6 units in control groups (p=0.17). Hypokalemia occurred in three patients in intervention and four patients in control groups. In 35% of samples in intervention group and 51% in controls blood sugar was more than 10 mmol/l for 24 h after discontinuation of the insulin infusion (p=0.046). The mean duration of hospitalization was 5.1+/-1.88 in intervention and 5.9+/-2.19 d in control group (p=0.225). CONCLUSION: Adding GI to the standard treatment of DKA reduced average time of recovery from DKA, without incurring episodes of hypoglycemia and hypokalemia. This also reduced in the time of recovery from DKA, amount of required insulin and the duration of hospitalization. It seems that the non significant difference in the time of recovery from DKA be related to the small sample size and study design. Further studies are recommended. PMID- 26155507 TI - Coronary Artery Disease Risk Factors, Coronary Artery Calcification and Coronary Bypass Surgery. AB - INTRODUCTION: Atherosclerosis is an intimal disease which affects large and medium size arteries including aorta and carotid, coronary, cerebral and radial arteries. Calcium accumulated in the coronary arterial plaques have substantial contribution to the plaque volume. The aim of our study is to investigate the relationship between coronary artery disease (CAD) risk factors and coronary arterial calcification, and to delineate the importance of CACS in coronary artery bypass surgery. MATERIALS AND METHODS: The current study is retrospective and 410 patients admitted to our clinic with atypical chest pain and without known CAD were included. These individuals were evaluated by 16 slice electron beam computed tomography with suspicion of CAD and their calcium scores were calculated. Detailed demographic and medical history were obtained from all of the patients. RESULTS: In our study, we employed five different analyses using different coronary arterial calcification score (CACS) thresold levels reported in previous studies. All of the analyses, performed according to the previously defined thresold levels, showed that risk factors had strong positive relationship with CACS as mentioned in previous studies. CONCLUSION: Coronary arterial calcification is part of the athero-sclerotic process and although it can be detected in atherosclerotic vessel, it is absent in a normal vessel. It can be concluded that the clinical scores, even they are helpful, have some limitations in a significant part of the population for cardiovascular risk determination. It is important for an anastomosis region to be noncalcified in coronary bypass surgery. In a coronary artery, it will be helpness for showing of calcific field and anostomosis spot. PMID- 26155508 TI - Erasmus Syndrome in a 42-Year-Old Male: A Rare Case Report. AB - Erasmus syndrome is a rare entity in which systemic sclerosis develops following exposure to silica with or without silicosis. Few case reports are available in literature. We report here a case of Erasmus syndrome in a 42-year-old manual labourer. The patient presented with arthralgia, Raynoud's phenomenon, skin tightening and microstomia along with features of Interstitial Lung Disease (ILD) and pulmonary arterial hypertension. Evidence of Interstitial Lung Disease (ILD) with mediastinal lymphadenopathy as well as pulmonary arterial hypertension with vascular reactivity was found in appropriate investigations. Serological markers of systemic sclerosis were strongly positive. After a diagnosis of Erasmus syndrome was made, a combination of drugs including Prednisone, Cyclophosphamide and Nifedipine was instituted this led to moderate improvement in his symptoms over 6 months. PMID- 26155509 TI - Bindi Tuberculosis - Lupus Vulgaris Associated with Bindi Use: A Case Report. AB - Cutaneous lesions are relatively uncommon manifestations of tuberculosis (TB). A 40-year-old female presented with skin lesion over the forehead since two months. She used to apply bindi over the same area since past 25 years. Based on skin biopsy and other ancillary investigations, she was diagnosed as a case of lupus vulgaris and initiated on anti TB medications following which, the lesion regressed. Thus, we herein report the first case of cutaneous tuberculosis (lupus vulgaris) associated with long term use of bindi. PMID- 26155510 TI - Acute Kidney Injury and Quadriparesis Due to Rosuvastatin Induced Rhabdomyolysis- A Case Report. AB - Statins as lipid lowering drugs, are safe and effective in reducing cardiovascular disease risk, but rarely produce myopathy like myalgia, myositis or rhabdomyolysis. We report the case of Rosuvastatin induced rhabdomyolytic acute renal failure and quadriparesis in a 67-year old male, a known case of type 2 diabetes mellitus and with a history of coronary angioplasty four months back. He was on antihypertensive, oral hypoglycemic and antiplatelet medications with Rosuvastatin 40mg/day. He was admitted with altered sensorium, breathlessness, vomiting, muscle weakness and decreased urine output and had raised serum creatinine, creatinine phosphokinase and myoglobin. After ruling out all other causation for rhabdomyolysis, we stopped Rosuvastatin and started supportive management and hemodialysis. Patient showed gradual recovery in renal function and quadriparesis. Patient was discharged with good urine output and on antihypertensive, hypoglycemic drug and diet restrictions for lipid control. He recovered completely and had normal renal function with well controlled lipid level on follow up of 6 months after discharge. Thus, prompt diagnosis of Rhabdomyolysis due to Rosuvastatin in absence of other aetiology and the multidisciplinary management can prevent further complication with favorable outcome. PMID- 26155511 TI - Scrub Typhus with Acute Respiratory Distress Syndrome (ARDS) and its Management in Intensive Care Unit: A Case Report. AB - Scrub typhus is zoonotic disease caused by Orientia tsutsugamushi (O tsutsugamushi). It is transmitted to humans by the bite of trombiculid mite larvae (chiggers). It is a re-emerging infectious disease in India. Clinical manifestations include fever, headache, anorexia, myalgia, eschar, adenopathy and maculopapular rash. Complications of Scrub typhus develop after first week of illness. Complications include meningoencephalitis, jaundice, myocarditis, ARDS and renal failure. Eschar and rash may be unnoticed or absent. Thorough physical examination, identification of eschar/rash throws light in thinking about scrub typhus, treating and preventing further complications. Here, we report a case of scrub typhus with Acute Respiratory Distress Syndrome (ARDS) and its management with non invasive ventilation in the intensive care unit. PMID- 26155512 TI - Transient 2(nd) Degree Av Block Mobitz Type II: A Rare Finding in Dengue Haemorrhagic Fever. AB - Dengue has been a major problem as endemic occurs almost every year and causes a state of panic due to lack of proper diagnostic methods and facilities for proper management. Patients presenting with classical symptoms are easy to diagnose, however as a large number of cases occur every year, a number of cases diagnosed with dengue fever on occasion presents with atypical manifestations, which cause extensive evaluation of the patients, unnecessary referral to higher centre irrespective of the severity and therefore a rough idea of these manifestations must be present in the backdrop in order to prevent these problems. Involvement of cardiovascular system in dengue has been reported in previous studies, and they are usually benign and self-limited. The importance of study of conduction abnormalities is important as sometimes conduction blocks are the first sign of acute myocarditis in patients of Dengue Hemorrhagic Fever in shock. We present here a case of 2(nd) Degree Mobitz Type II atrioventricular AV block in a case of Dengue Hemorrhagic fever reverting to the normal rhythm in recovery phase and no signs thereafter on follow up. PMID- 26155513 TI - Multiple Sclerosis Like Condition in a Patient of Hepatitis C after Treatment with Interferon Alpha: A Case Report. AB - Hepatitis C virus affects millions of people around the world. The primary therapy comprises of interferon alpha and ribavarin. The most common side effects of this treatment include flu like symptoms and psychiatric issues. One of the rare complications of the combined therapy is the development of demyelinating lesions in the central nervous system. Our case report presents a 35-year-old man who was a known case of Hepatitis C presenting to us with altered level of consciousness and decreased vision. He had been treated as per the standard therapy for Hepatitis C infection with interferon alpha and ribavarin. During the course of this therapy, he developed significant loss of vision. This was in fact due to serious and rare complication of the treatment which was demonstrated on the MRI as demyelinating lesions in the deep periventricular white matter bilaterally. Visual Evoked Potential study was performed which concluded bilateral dysfunction of the optic pathway. The treatment of Hepatitis C with interferon alpha and ribavarin may present with a wide array of adverse effects which includes a rare complication of central nervous system demyelination as well. Research suggests that early treatment of Multiple Sclerosis (MS) is beneficial in the long run with a better prognosis and minimal changes on MRI of the patient. Therefore this complication of the treatment should be kept in mind as one of the main differential diagnosis. By finding the extent of the inflammation, and consequently doing an MRI alongside a lumbar puncture, can serve to diagnose a rare condition mimicking multiple sclerosis while treating with interferon alpha. PMID- 26155514 TI - Immunization in Patients with Rheumatic Diseases: A Practical Guide for General Practitioners. AB - Patients with rheumatic diseases are susceptible to various infections throughout the course of the disease. The increased risk of infections can be attributed partly to the aberrant immune system and partly to the effect of immunosuppressive drugs used in the treatment of the disease. Immunization appears to be an excellent strategy to prevent infections in such patients. However, the effect of vaccines in these patients is modified due to disease per se and/or immunosuppressive drugs. Biological agents, that frequently increase the susceptibility to infections, are now being initiated earlier in the course of the disease and also for new indications. Thus, concerns regarding safety, efficacy and potential adverse effects of vaccines in these patients are more complex than in any other immunosuppressive conditions. Different patients show different amount of immunosuppression in response to disease modifying drugs. Besides, there is lack of adequately powered randomised controlled trials investigating the efficacy of a vaccine in terms of actual prevention of the disease. Pneumococcal and influenza vaccines are the most studied vaccines and they are strongly recommended in rheumatic patients. In general, live vaccines should be avoided among patients receiving high doses of immunosuppressive drugs. However, they may be given to patients receiving low dose steroids and methotrexate. Non-live vaccines may be administered as per the recommendations of national guidelines. There is necessity to increase awareness among patients and doctors towards promoting the appropriate and judicious use of vaccines in the patients with rheumatic diseases. PMID- 26155515 TI - Relationship Between Second to Fourth Digit Ratios and Benign Prostatic Hyperplasia in Aging Men. AB - INTRODUCTION: Benign prostatic hyperplasia (BPH) is the most common prostate disease, characterized by benign enlargement of the prostate gland in aging men. Testosterone is said to be the major factor in development of BPH. The relative length of 2nd and 4th digit (2D:4D) is a marker for prenatal androgen exposure. A low 2D:4D ratio is associated with a high prenatal androgen exposure. The main objective of this study was to assess the causal relationship between the 2D:4D ratio and incidence of BPH. MATERIALS AND METHODS: Thirty five patients with BPH were compared with 35 non BPH subjects and 35 controls recruited from general population for measures of 2D:4D ratio. BPH status was determined by clinical & radiological evaluation. Both hands of all the participants were scanned and their second and fourth digit lengths were measured and the ratio calculated. RESULTS: In the present study, 2D:4D ratio was lower in BPH patients compared to non BPH subjects in both hands. Compared with controls, BPH patients had lower 2D:4D ratio in the right hand, but the difference between the groups in left hand 2D:4D ratios was not significant. Compared with controls, non BPH subjects had higher 2D:4D ratio in the left hand, but the difference between the groups in right hand 2D:4D ratios was not significant. CONCLUSION: Results of the present study indicate that individuals with lower 2D:4D ratios are at a higher risk of developing BPH and those with higher 2D:4D ratios are at a lower risk of developing BPH compared to the general population. PMID- 26155516 TI - Surgery for Colorectal Cancer in Elderly Patients: How Could We Improve Early Outcomes ? AB - BACKGROUND: Age is one of the causes behind the undertreatment of elderly colorectal cancer patients. The increase of mortality among elderly colorectal cancer (CRC) patients is due to competing causes of death occurring in the early post operative period. The purpose of this study was to evaluate the risk factors for post operative mortality and morbidity among elderly CRC patients. MATERIALS AND METHODS: A retrospective descriptive chart review was performed on consecutive patients older than 70 y with CRC. We have collected data of 124 patients who were admitted from January 2001 to January 2010. Demographic characteristics, operative and postoperative informations were retrospectively analysed. RESULTS: Early postoperative morbidity, operation related to morbidity and mortality were observed in 44 (35.5%), 9 (7.3%) and 20 (16.1%) cases, respectively. No other factors but ASA score (p = 0.002 and 0.005 in univariate and multivariate analyses, respectively) and emergency operations (p<0.001 and 10(-3) in univariate and multivariate analyses, respectively), were found to be risk factors of mortality. The results of multivariate analyses indicated that anaemia (p=0.021) and rectal cancer (p=0.015) had significant impact on the risk of anastomotic leakage. On the other hand, diabetes mellitus and rectal cancer were indicators that correlated with the width of hospitalization. CONCLUSION: Elderly CRC patients should no longer be undertreated only because of their age. They should be exposed to more aggressive management than they are currently receiving. Careful preoperative evaluation, followed by medical optimization and planning of perioperative care could improve outcomes of colorectal surgery for elderly patients. PMID- 26155517 TI - Splenic Injury in Situs Inversus Totalis - A Surgical Challenge. AB - Situs inversus totalis is a rare congenital anomaly in which position of the heart and all abdominal viscera is reversed. Situs abnormalities usually go unnoticed but may be recognized by radiography or ultrasonography as an incidental finding or during evaluation for congenital heart diseases. We present such an extremely rare and to the best of our knowledge the third reported case of an injured spleen in the right hypochondrium, following seemingly trivial blunt trauma in a patient with situs inversus totalis who underwent splenectomy. The presence of associated congenital heart defects, visceral anatomical variations and mirror imaging makes the anaesthetic management as well as the surgical exercise a challenging one in such cases. PMID- 26155518 TI - Congenital Bilateral Mid Ureteral Stenosis: A Rare Finding. AB - Bilateral congenital mid ureteric stenosis is a very rare entity causing hydroureteronephrosis. The pathophysiology and aetiology of this condition is uncertain. Congenital functional obstruction of the mid ureter has only 17 reported cases, that too of unilateral pathology. We report a case of an 11-year old male child who was presented with left sided lump in abdomen since one year. On bilateral retrograde ureteropyelography (RGP), bilateral mid ureteric stenosis was documented at the level of pelvic brim. Tc99m Diethylene Triamine Pentacaetic Acid (DTPA) scan showed non functioning left kidney and decreased function and retention on right side. We did a left nephroureterectomy and uretero ureterostomy without tapering over a Double-J stent (DJ), with excision of stenosed segment on right side. Pathological review of the ureteric segments of both sides revealed proximal dilatation with non-specific thickening of the muscular wall of the stenosed segments of ureter. The differential diagnosis must additionally include ureteral valves and fibro epithelial polyps. Important role of intravenous pyelography in such cases must be emphasized to localize the pathology site. In addition, retrograde ureteropyelography is essential in management of this anomaly to delineate the stenosed segment of the ureter preoperatively, so that the surgeon can be well prepared with final plan of management. PMID- 26155519 TI - Uncommon Surgical Causes Of Right Lower Quadrant Pain In Children. Single Center Experience. AB - Right lower quadrant pain is one of the major reasons of children reference at the emergency department. The most common surgical cause, which needs appropriate management, is acute appendicitis. The purpose of this study is to reveal uncommon surgical causes found during surgery in children who were misdiagnosed as acute appendicitis in our department during the last 10 y. Data of patients who have undergone appendicectomy during a ten year period (since Feb 2004 until Mar 2014) were collected retrospectively. Eight hundred twenty children have undergone appendicectomy in our department. In six children another uncommon cause of the symptoms was revealed during surgery. In one patient the cause was a duplication cyst of the terminal ileum, in two patients an omental torsion, in one patient a meckel diverticulum torsion, in one patient a splenic rupture and in one patient a retroperitoneal tumor. All of the patients were successfully managed during the first operation. The possibility of other uncommon causes of right quadrant abdominal pain should always be kept in mind, especially when there is a negative appendicitis. However, the transaction of further paraclinical examinations - ultrasonography or computed tomography- preoperatively is under discussion. Nevertheless a thoroughly taken case history is undoubtedly always necessary. PMID- 26155520 TI - Effect of Infertility on Sexual Function: A Cross-Sectional Study. AB - INTRODUCTION: Sexual dysfunction is an important psychological disorder that may increase in infertile couples. AIM: To evaluate the effect of infertility on sexual function in women attending in private and public institutions in Ilam during 2013. MATERIALS AND METHODS: In a cross - sectional study evaluated the sexual function among 384 women attending in health care centers of Ilam western of Iran during 2013. Participants were divided in two groups, fertilities and infertilities women. Data was collected by trained research midwives using demographic and FSFI questionnaires. SPSS software Package 16 was used to analyse the data of this project. Differences were regarded statistically significant with an alpha error of 0.05. RESULTS: The mean age was 29.29 +/- 6.7 years in fertile and 31.74 +/- 8.07 in infertile women. Significant difference was reported in mean age between fertile and infertile women (p=0.014). The Mean+/- SD of all demissions of female sexual function was difference between fertile and infertile women. Sexual function was lower in infertile women. CONCLUSION: All dimensions of sexual function were lower in infertile women in compared with fertile women. Further research should be done on this subject and ways to address such problems should be found. PMID- 26155521 TI - Manipal Cervical Scoring System by Transvaginal Ultrasound in Predicting Successful Labour Induction. AB - INTRODUCTION: Induction of labour (IOL) nowadays is a common procedure in obstetric practice. The success of IOL largely depends upon "favourability" or "readiness" cervix which is traditionally assessed by manual examination and Scored as Bishop Score. However, this method is limited by subjectivity and reproducibility and though done in all the patients prior to IOL, several studies have demonstrated poor correlation between Bishop Score and outcome of labour. OBJECTIVE: To evaluate the role of preinduction transvaginal ultrasonographic (TVS) cervical assessment in predicting labour outcome and to compare its performance against Bishop Score in patients undergoing induction of labour (IOL). SETTING: A tertiary medical college hospital in Southern India. DESIGN: Prospective observational and investigational study. MATERIALS AND METHODS: Transvaginal ultrasound was performed in 131 patients who underwent labour induction at term with intact membranes and live fetus. Bishop Score was assessed by pervaginal examination and was compared with preinduction TVS cervical Score (parameters being cervical length, funneling, position of cervix and distance of presenting part from external os). Labour was induced within one hour of cervical assessment. The labour induction was considered successful if patient could get into active labour i.e., onset of regular uterine contractions (at interval of 2 3 minutes) and cervical dilatation of 4 cm or greater within 24 hours of induction. RESULTS: Labour induction was successful in 86.9% of patients. At cut off Scores of >= 4, TVS cervical Score performed better than Bishop Score (Sensitivity 77% vs. 65%, Specificity 93% vs. 86%). ROC analysis indicated that Area Under Curve (AUC) was more for TVS Score (0.90, 95% CI 0.84 - 0.95), compared to Bishop Score. It was found that an increase in cervical length and distance from the os by 1 mm from their means were associated with an increase in odds for failure of induction and there by caesarean delivery by 6.5% and 11% respectively. CONCLUSION: In women experiencing labour induction, transvaginal ultrasound score comprising of five different parameters indicated success of induction better than Bishop Score. Further, two of its components (longer cervical length and increased distance of presenting part from external os) demonstrated significant and independent prediction of the likelihood of failure of induction and risk of operative delivery. PMID- 26155522 TI - Spontaneous Fingertip Endometriosis: A Rare Case Report. PMID- 26155523 TI - Lumbar Apophyseal Ring Fracture- A Case Report. AB - Posterior apophyseal ring fracture is a rare condition typically seen in adolescent age group because the ring apophysis and the adjacent vertebral body does not fuse completely and may separate at the cephalad or caudal edge. It usually simulates disc herniation in adolescents and children but disc lesion is very commonly associated with PRAF. The condition although is rare but a high index of suspicion should be there during evaluation of any adolescent patient with low back ache as it is often missed on conventional radiography. Multiple treatment options have been described in literature, both conservative and surgical. We hereby report a case of posterior apophyseal ring fracture with a calcified disc adherent to the dura for which decompression alone without discectomy was found to be an effective treatment. PMID- 26155524 TI - Neglected Thorn Injury Mimicking Soft Tissue Mass in a Child: A Case Report. AB - Thorn injuries are common especially in rural areas. The diagnosis of such in children is always missed. An untreated retained thorn may cause late soft tissue and osseous complications. Herein, we report a case of neglected thorn injury mimicking soft tissue mass in an 11-year-old male child. The presence of the thorn was confirmed with ultrasound scan and computerized tomography. The child was successfully managed with removal of thorn with excision of foreign body granuloma. PMID- 26155525 TI - A Study on Longevity of Immune Response after Vaccination with Salmonella Typhi Vi Conjugate Vaccine (PedatyphTM) in Children. AB - BACKGROUND AND OBJECTIVES: Owing to the limitations of the conventional polysaccharide vaccines, global efforts have been made to develop conjugated polysaccharide vaccines for typhoid. Duration of immune response induced by these vaccines is critical to define the efficacy and frequency of required booster dose. This study was done to determine the duration of immune response following vaccination with Salmonella Typhi Vi conjugate vaccine (PedatyphTM) in children and to assess the booster effect of second dose of conjugate typhoid vaccine. MATERIALS AND METHODS: Forty children were recalled from a cohort of 400 children, who received one dose or two doses of PedaTyphTM, 30 months after vaccination. Ten non-vaccinated children were also recalled. Their serum samples were assessed by ELISA for anti Vi antibody. RESULTS: Significantly high titers of anti-Vi polysaccharide IgG antibodies were present in vaccinated children even after 30 months of vaccination as compared to non-vaccinated children. Geometric mean titers (GMT) with 95% confidence intervals were 14 (4.8-29.8), 17 (7.4-33) and 6.4 (0.8-12) MUg/ml for single dose, two doses and control group respectively. The children in two doses group had higher antibody titers as compared to single dose group. However, the difference was not significant. INTERPRETATION AND CONCLUSION: PedaTyphTM was found to induce long term immune response as evidenced by presence of significant anti-Vi polysaccharide antibodies after 30 months of vaccination. No significant advantage of two doses regimen over one dose was found. Hence one dose vaccination with PedaTyphTM is suggested. PMID- 26155526 TI - Chronic Granulomatous Disease. AB - Chronic Granulomatous Disease (CGD) is an inherited immunodeficiency disorder characterized by defective functioning of NADPH oxidase enzyme in the phagocytes. This leads to recurrent infections by catalase positive organisms and later, granuloma formation in multiple organs. This condition usually presents in the age group of 2-5 y and is uncommon in neonates. In this case report, we describe a rare case of CGD in a 40-day-old male child who initially presented with a history of erythematous pustular rash on left forearm and refusal to feeds. He remained unresponsive to regular antibiotics. CT chest and abdomen revealed multiple ill-defined lesions suggestive of granulomas or developing abscesses. Immunodeficiency workup showed negative Nitroblue Tetrazolium test and positive Dihydrorhodamine test (flow cytometry). A diagnosis of CGD was then made and treated accordingly. The aim of this report is to highlight the fact that although it is rare for CGD to present at such an early age, but in a neonate with multiple granulomas or abscesses, it should be considered as a differential and worked up accordingly. Early diagnosis and treatment can significantly improve the prognosis. PMID- 26155527 TI - Case Presentation of a 23-Month-old Herpes Simplex Virus-infected Girl with Brain and Oesophageal Involvement. AB - Herpes simplex virus (HSV) is the most common identifiable cause of serious or life threatening sporadic, endemic encephalitis. Typical HSV encephalitis in patients outside neonatal age is caused by HSV-1. A 23-month-old girl was referred to our hospital with a three-day history of fever, listlessness, slurred speech, and suspicious oesophageal foreign body impaction. Laboratory evaluations showed white blood cell count of 10900 /mm3 with 65% neutrophils. Upper endoscopy revealed diffuse severe ulceration in middle to distal third of oesophagus and no foreign body was found in oesophagus or stomach. Parenteral acyclovir was prescribed for herpes encephalitis in addition to antibiotics for central nervous system infection. Chest X-ray and brain MRI was unremarkable. Lumbar puncture revealed normal protein and glucose with 10 white cell count. She developed a raising liver enzyme tests. Total and direct bilirubin was 1.2 mg/dc and 0.2 mg/dc respectively. Because of neurological symptoms, acyclovir was adopted for our patient from the beginning. The girl did not respond to medication and died after 28 days. Progression of her disease prior to referral appears to contribute to the administered treatment inefficacy. Severe rapid progression of disease prior to referral and potential resistance to acyclovir could cause treatment failure. PMID- 26155528 TI - CT Perfusion Dynamics of Intracranial Tuberculomas. AB - AIMS: To study perfusion characteristics of intracranial tuberculomas and analyze changes with anti tubercular treatment. MATERIALS AND METHODS: Nineteen patients of histologically proven intracranial tuberculomas were included in the study of which 9 were not on antitubercular treatment and ten were on antitubercular treatment (6 patients on treatment for less than 2 months and 4 were more than 6 months). All patients underwent CT perfusion (CTP) and CTP parameters like rCBV and rCBF were obtained from entire lesion, center and capsule of lesions and compared. RESULTS: CTP parameters like rCBF and rCBV were significantly low in all the three ROIs in the group not on treatment compared to that of on treatment ; rCBF and rCBV of entire lesion (p=0.018 and p=0.005 respectively), capsule (p=0.045 and p=0.010 respectively) and center of the lesion (p=0.020 and p=0.009) respectively). Tuberculomas on antitubercular treatment of more than six months showed reduced rCBF and rCBV in entire lesion (p=0.01 & p=0.01 respectively), capsule (p=0.04 & p=0.03 respectively) and center (p=0.08 & p=0.05 respectively) compared to those on treatment for less than two months. Similarly tuberculomas on treatment for six months did not show significant difference in rCBF and rCBV compared to tuberculomas who were not on treatment. Tuberculomas on treatment for less than two months showed statistically increased rCBF and rCBV in entire lesion (p=0.01 & p=0.04 respectively), capsule (p=0.03 & p=0.01 respectively) and center (p= 0.03 &=0.01) compared to those not on treatment. CONCLUSION: Intracranial tuberculomas not on treatment and those on treatment for around six months show low perfusion and tuberculomas on treatment for less than two months show high perfusion. These findings suggest that serial perfusion profiles of tuberculomas on treatment could possibly be seen as surrogate markers of response to treatment. PMID- 26155529 TI - Subhallucal Interphalangeal Sesamoiditis: A Rare Cause of Chronic Great Toe Pain. AB - Subhallucal interphalangeal sesamoiditis presenting as chronic great toe pain is a rarely reported clinical entity, being often overlooked and misdiagnosed for other pathologies. By altering the biomechanics of the movements at great toe, the interphalangeal sesamoid is prone to various painful pathologies like trauma, infection, degeneration, osteonecrosis and inflammation. Imaging plays an important role in narrowing down the differentials and guiding for appropriate therapy. Herein, we present a neglected case of hallucal interphalangeal sesamoiditis presenting as a case of chronic great toe pain and discuss the role of Magnetic resonance imaging (MRI) and Computed tomography (CT) scan in its diagnosis. PMID- 26155530 TI - Unilateral Obstructive Emphysema in Infancy due to Mediastinal Bronchogenic Cyst Diagnostic Challenge and Management. AB - Bronchogenic cysts are the most common cystic mediastinal lesion in children. Bronchogenic cyst causing unilateral obstructive emphysema is a rare presentation. We report the case of a one and half month old infant who presented with respiratory distress which was initially suspected as left pneumothorax on frontal chest radiograph but was later found to be due to hyperinflated left lung and hence the possibility of congenital lobar emphysema was considered. CT thorax and limited MRI sections revealed a cystic lesion in mediastinum causing obstructive emphysema and mediastinal displacement. He underwent an emergency thoracotomy and excision of the cyst via an extrapleural approach. Post operatively, rapid improvement of the infant was noticed both clinically as well as radiologically. Cross sectional imaging like CT or MR is required for reaching the correct and early diagnosis in paediatric patients with respiratory distress, when there is diagnostic dilemma based on chest radiograph. PMID- 26155531 TI - Imaging Diagnosis of Herlyn-Werner-Wunderlich Syndrome- An Extremely Rare Urogenital Anomaly. AB - Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital anomaly of the urogenital tract resulting from maldevelopment of both Mullerian and Wolffian ducts. It is characterized by the triad of uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis. It generally presents at puberty shortly following menarche with the symptom of acute pelvic pain. Management of these cases is surgical and consists mainly of vaginoplasty with excision of the vaginal septum in order to release the obstruction and prevent the long term complication of recurrent pyocolpos and infertility. We report here a case of Herlyn-Werner-Wunderlich syndrome in a 13-year-old adolescent girl, emphasizing the role of imaging in the accurate and prompt diagnosis of this rare developmental urogenital anomaly. Only a few hundred such cases have been reported in literature till date. PMID- 26155532 TI - Case Report - Pyknodysostosis. AB - Pyknodysostosis is an extremely rare lysosomal storage disease of the bone. Osteosclerosis of the skeleton is due to a decrease of the bone turnover. A plethora of clinical and radiological findings are observed. Patients are short statured with acroosteolysis and dense bones and develop multiple spontaneous bone fractures. A female patient presented with frontal bossing, small and thick fingers and toes. The classical clinical and radiological findings confirmed it as pyknodysostosis. PMID- 26155533 TI - "Inverted V sign" in Sub-Acute Combined Degeneration of Cord. PMID- 26155534 TI - Comparison of Efficacy of Clonidine versus Ondansetron for Prevention of Nausea and Vomiting Post Thyroidectomy: A Double Blind Randomized Controlled Trial. AB - BACKGROUND AND AIM: Postoperative nausea vomiting (PONV) is the most common symptom in patients post thyroidectomy. Literature search shows conflicting results regarding use of clonidine in PONV prophylaxis. We undertook this randomized controlled double blind trial to compare the efficacy of clonidine with dexamethasone versus ondansetron with dexamethasone for PONV prophylaxis in these patients. MATERIALS AND METHODS: In this prospective study, 60 consecutive patients posted for thyroidectomy from August 2013 to July 2014, were randomly assigned to two groups, ondansetron (N= 30) (Group A) and clonidine (N= 30) (Group B). Patients received either oral ondansetron 8mg or oral clonidine 150MUg as premedication. At the end of surgery, both groups received dexamethasone 8mg intravenously. They were monitored for occurrence of PONV and sore throat for next 24 h. Ramsay sedation scores and total time of analgesia was noted. The primary end point was incidence of PONV in post operative for 24 h. Pearson's chi square test and Students t tests were performed using SPSS for windows version 20 (SPSS Inc., Chicago, IL). RESULTS: Baseline characteristics of patients were comparable. A higher proportion of patients in clonidine group developed PONV than ondansetron (36.7% vs 30%; p=0.03). Clonidine group patients experienced early nausea and vomiting (1-2hrs of postoperative period), compared to ondansetron group patients (6-12 h). Ramsay sedation scores at arrival were higher in clonidine group compared to ondansetron group (2.1 +/- 0.3 versus 2.0; p=0.003). Total time of analgesia was higher with use of clonidine than ondansetron (919.5 +/- 622 mins versus 642 +/- 631 mins; p=0.09). Moderate sore throat was seen in 2 out of 30 patients in both groups. No major adverse events were observed in either group. CONCLUSION: Ondansetron with dexamethasone group was more effective in controlling PONV after thyroidectomy compared to clonidine with dexamethasone group. However, ramsay sedation scores and total time of analgesia were higher with clonidine than ondansetron. PMID- 26155535 TI - Bilateral Infraorbital Nerve Block Versus Intravenous Pentazocine: A Comparative Study on Post-operative Pain Relief Following Cleft Lip Surgery. AB - BACKGROUND AND OBJECTIVES: Infra orbital nerve block is utilized for postoperative pain control in children undergoing cleft lip repair. This study was conducted to compare the effectiveness, advantages and disadvantages of infra orbital nerve block and opioids for postoperative pain relief following cheiloplasty. MATERIALS AND METHODS: Sixty paediatric patients aged 3 months - 13 years undergoing cheiloplasty were selected by simple random sampling and were divided into two groups. All the children received standardized premedication with midazolam, were operated upon under general anaesthesia and the block was performed at the end of surgery before reversal. Group B patients were administered bilateral infra orbital nerve block with 0.25% Bupivacaine (upto 2 mg/kg). Group O patients received Pentazocine 0.5 mg / kg IV. Postoperatively, the heart rate and respiratory rates were recorded every 15 minutes for the first 60 minutes, half hourly till 4 hours and then at 12 and 24 hours. Behavioural assessment for pain / discomfort was done at intervals of 1/2, 1, 2, 3, 4, 12 and 24 hours. Need for supplementary analgesics and duration between the administration of block/opioid and the first dose of supplementary analgesics were noted. Side effects such as nausea and vomiting, pruritus, respiratory depression and bradycardia during each of these periods were noted. RESULTS: Both the groups were comparable for age, sex, weight and operative time with no statistical difference. The mean duration of analgesia for infra orbital nerve block was 357.5 minutes i.e. 5 hours 58 minutes and that for opioid was 231 minutes i.e. 3 hours 51 minutes which was significantly lower than the hours of analgesia provided by the block. Further, at the 4th hour, 76.6% of the patients in Group O required supplementary analgesics, in contrast to only 16.6% in Group B. The incidence of nausea and vomiting and pruritus was also higher in Group O. CONCLUSION: The results indicate that bilateral infra orbital nerve block provides effective analgesia in the postoperative period, lasting for 6 hours in comparison to 31/2 - 4 hours following the administration of intravenous Pentazocine, with no major untoward effects. PMID- 26155536 TI - BIS Targeted Propofol Sparing Effects of Dexmedetomidine Versus Ketamine in Outpatient ERCP: A Prospective Randomised Controlled Trial. AB - BACKGROUND: Endoscopic Retrograde Cholangio Pancreatography (ERCP) is routinely performed under propofol sedation. Adjuvant drugs have improved the quality of propofol sedation while minimizing complications. The aim of the study was to compare the propofol consumption, recovery and hemodynamic profiles of dexmedetomidine versus ketamine against a placebo control with BIS targeted in the sedative range for outpatient ERCP procedures. MATERIALS AND METHODS: The study comprised of 72 patients undergoing ERCP, who were randomly allocated into one of the 3 groups: Group Dexmedetomidine (n =24) receiving a bolus and infusion of dexmedetomidine (1MUg/kg and 0.5MUg/kg/hr); Group Ketamine (n = 24) receiving a bolus and infusion of ketamine (0.25mg/kg and 5MUg/kg/min) and Group Control (n =24) receiving saline placebo as a bolus and infusion with variable propofol boluses administered in all groups targeting BiSpectral Index between 60-70. RESULTS: The total propofol consumption was significantly lower in both Dexmedetomidine (162.5 +/- 71.7 mg ) and Ketamine groups (158.3 +/- 66.89 mg) when compared with Control group (255.83 +/- 114.12 mg)(p=0.001) .Time taken (minutes) to achieve Modified Aldrette Score (MAS) >9 and Observer Assessment of Alertness and Sedation (OAAS) score >4 was significantly prolonged in Dexmedetomidine group (MAS 16.6 +/- 3.18 and OAAS 16.67 +/- 2.82) compared to Ketamine (MAS 10 +/- 4.17 and OAAS 8.75 +/- 3.68) and Control (MAS 7.5 +/- 3.29 and OAAS 6.88 +/- 2.47) (p<0.001). Hemodynamic profiles were comparable although patients in dexmedetomidine had a statistically significant lower heart rate (p<0.001) although without clinical significance. CONCLUSION: Low dose ketamine with background propofol boluses resulted in lesser propofol consumption, with earlier recovery and favourable hemodynamics when compared with Dexmedetomidine and control group in outpatient ERCP. PMID- 26155537 TI - Anaesthesia for a Rare Case of Down's Syndrome with Morgagni's Hernia Undergoing Laparoscopic Repair. AB - Morgagni's hernia is a type of congenital diaphragmatic hernia and it is rare in children. The association between Down's syndrome and Morgagni's hernia in children is also rare. Laparoscopic repair is a preferred surgical approach than open surgical procedures as laparoscopy offers a bilateral view of Morgagni's hernia, minimal tissue damage and a faster recovery. When children with Down's syndrome and associated Morgagni's hernia present for laparoscopic repair, they pose several complex challenges to the anaesthetist due to the involvement of multiple organ systems, difficulties in airway management and effects of laparoscopic surgery on the organ systems. Therefore, such children need a very careful anaesthetic plan, including a thorough preoperative assessment and preparation for a successful perioperative outcome. PMID- 26155538 TI - A Safe Alternative in Neurofibromatosis for Lower Limb Surgeries: Combined Femoral and Sciatic Nerve Block. AB - Neurofibromatosis (NF) is a neurogenetic disease with multiple systemic involvement. In this case report we describe the successful management of a patient with NF posted for lower limb wound debridement with multiple neurofibromas over the back and face causing difficulty in spinal anesthesia and general anaesthesia. Combined femoral and sciatic nerve block was used as a safe alternative anaesthetic approach. PMID- 26155539 TI - Which is A More Debilitating Disorder Schizophrenia or Dysthymia? - A Comparative Study. AB - INTRODUCTION: Schizophrenia and Dysthymia are debilitating disorders that affect general health and functioning. Studies show that both vastly affect the quality of life (QOL) of patients and cause great amount of disability. OBJECTIVE: To evaluate and compare the QOL and Disability between patients with Schizophrenia and Dysthymia. MATERIALS AND METHODS: A cross sectional, observational, comparative study was done in a randomly chosen sample of 30 outpatients each of schizophrenia and dysthymia. QOL was assessed using WHOQOL-BREF scale and disability was assessed using the Indian Disability Evaluation and Assessment Scale (IDEAS). RESULTS: Patients of schizophrenia showed greater disability and poorer QOL than patients of dysthymia. The 'Social Relationships' domain of the WHOQOL-BREF scale was the worst affected domain in both groups of patients. Patients with dysthymia also did significantly (p=0.040) better in the 'Psychological' domain; while patients with schizophrenia were significantly (p=0.029) better in the 'Physical Health' domain. Patients with schizophrenia showed greater disability than patients with dysthymia in all the 4 domains of the IDEAS, significantly in the areas of Self care (p<0.001) and Communication Understanding (p<0.001). CONCLUSION: Schizophrenia is a more debilitating disorder than Dysthymia. This assumes significance when planning rehabilitation models for these disorders. PMID- 26155540 TI - Assessment of Quality of Life (QOL) in Obsessive Compulsive Disorder (OCD) and Dysthymic Disorder (DD): A Comparative Study. AB - INTRODUCTION: There is paucity of data on Quality of Life (QOL) in non-psychotic mental disorders. AIM: To assess the Quality of Life (QOL) in Obsessive Compulsive Disorder (OCD) and compare it with Dysthymic Disorder (DD). MATERIALS AND METHODS: This hospital based cross-sectional study was conducted in 30 patients each diagnosed to have OCD and DD during October 2009 to September 2011 in a medical institution in Davanagere, Karnataka, India. DSM-IV-TR (Diagnostic statistical manual-IV-Text Revised) criteria was used for diagnosis of OCD and DD. Yale Brown Obsessive Compulsive Scale (Y-BOCS) and WHO QOL BREF (brief form) scales were used. Data was analysed by independent sample t-test. RESULTS: Overall QOL score was 51.07(SD=11.47) and 50.91(SD=7.41) in OCD and DD groups respectively. QOL score was comparatively low in psychological domain with score of 44.12(SD=14.14) and 45.10(12.35) in OCD and DD respectively. There was no significant difference in the QOL score of the two groups with respect to socio demographic variables in OCD group, but it was different with respect to place of residence in DD group (p<0.05). In Q1(perception on quality of life) and Q2 (perception on quality of health) domain, QOL score was marginally higher than average in both the groups. In Y-BOCS scale, no statistical significant association was found between severity of OCD and QOL score in each of the domains (p>0.05). CONCLUSION: Overall QOL score was average and there was no significant difference of QOL score between the OCD and DD groups implying that both these non-psychotic mental disorders may have same influence or effect on QOL of the subjects. Further analytical studies will explore the associated factors of QOL in OCD and DD. PMID- 26155541 TI - A Rare Case of Myxedema Coma with Neuroleptic Malignant Syndrome (NMS). AB - Myxedema coma or hypothyroid crisis is an endocrine emergency and needs ICU management. Neuroleptic malignant syndrome (NMS) is another medical emergency which needs high degree of clinical suspicion else mortality can be high. There is a paradox in co existence of myxedema coma and NMS. While one is hypometabolic state another is hypermetabolic state and both can be precipitated by antipsychotics use. Hypothermia and flaccidity commonly expected in myxedema coma may mask fever and rigidity of classical NMS contributing to diagnostic problem and treatment delay. Scientific literature on coexistance of myxedema coma and NMS is sparse. We hereby report first case with coexisting myxedema coma and NMS in a patient of schizophrenia treated with antipsychotic, where classical symptoms of NMS were masked by myxedema coma. Prompt diagnosis and effective management by a team resulted in favourable outcome in our patient. This case is reported to alert intensive care physicians to atypical manifestations of NMS in presence of hypothyroidism. PMID- 26155542 TI - Psychogenic Lingual Paresthesia. AB - Oral paresthesias are common in clinical practice but they often go unnoticed and untreated. Psychogenic oral paresthesia is an unpleasant sensation of tingling or pricking or a feeling of swelling or burning, with spontaneous onset.It can result due to local, systemic, psychogenic or idiopathic causes. Among psychogenic causes; anxiety disorder and depression are common. We describe a 32 year-old patient presented with lingual paresthesia and features suggestive of depression. He responded to an antidepressant, fluoxetine 40 mg /day. PMID- 26155543 TI - Auditory Hallucinations with an Unusual Content. AB - Recurrent hair pulling resulting in hair loss, in the absence of a medical or another mental disorder is a diagnostic feature of trichotillomania. It is commonly seen in depression and many other psychiatric disorders. Trichotillomania rarely occurs as a co morbid condition in patients with schizophrenia. Even rarer is recurrent hair pulling in response to psychotic symptoms in schizophrenia. We present the case of a young adult male who presented with recurrent hair pulling due to command auditory hallucinations and discuss the salient differentiating features of hair pulling seen in our patient and hair pulling in patients with trichotillomania. PMID- 26155544 TI - Solitary Angiokeratoma: Report of Two Uncommon Cases. AB - Angiokeratomas are rare benign vascular skin lesions arising in isolation or in groups of multiple lesions, as solitary cutaneous forms or generalized systemic forms. They are ectasias of dermal capillaries with an acanthotic and hyperkeratotic epidermis. They can occur in both healthy individuals and in those with underlying systemic disease due to inherited enzyme deficiency or other acquired predisposing factors. The identification and reporting of these lesions is important as patients with these lesions should be evaluated to rule out underlying pathogenic conditions. We report two rare cases of isolated solitary cutaneous angiokeratoma occurring in two patients. PMID- 26155545 TI - Comparison of Two Therapeutic Regimes, Lenalidomide with Dexamethasone and Thalidomide with Dexamethasone, in the Treatment of Multiple Myeloma at a Tertiary Care Hospital in India. AB - BACKGROUND: Multiple myeloma accounts for 1% of all neoplastic disorders and 10% of all haematological malignancies. Drugs like thalidomide, lenalidomide and bortezomib have emerged as active drugs in the treatment of multiple myeloma.There are few studies which have compared thalidomide-dexamethasone (thal/dex) and lenalidomide-dexamethasone (len/dex) in the treatment of multiple myeloma in Indian scenario. AIM: To compare the efficacy and the adverse events observed with thalidomide-dexamethasone and lenalidomide-dexamethasone in the treatment of newly diagnosed cases of multiple myeloma. SETTINGS AND DESIGN: Observational Study conducted in tertiary care centre. MATERIALS AND METHODS: The case record files of patients from the year January 2006 to July 2011 with diagnosis of multiple myeloma were studied. STATISTICAL ANALYSIS: Primarily Descriptive. RESULTS: There was no significant difference between thal/dex and len/dex treatment groups with respect to efficacy and safety in our study. CONCLUSION: Studies with larger sample size and a longer follow up to compare efficacy and safety of thal/dex and len/dex in treatment of multiple myeloma are required to be carried out to provide significant results. PMID- 26155546 TI - Giant Renal Mixed Epithelial and Stromal Tumour in A Young Female: A Rare Presentation. AB - Mixed epithelial and stromal tumour of the kidney (MESTK), is a rare kidney tumour. About 100 cases so far have been reported in the literature. Although MESTK mostly presents in perimenopausal age group some rare cases in young females have been reported. We report a rare presentation of a 25 cm size giant MESTK arising from the left kidney in a young female in the absence of any clinically detectable hormonal abnormalities and successfully managed by nephron sparing surgery. PMID- 26155547 TI - Malignant Peripheral Nerve Sheath Tumour of Small Intestine Presenting as Ileo Ileal Intussusception - A Rare Tumour with Unusual Complication. AB - Malignant Peripheral Nerve Sheath Tumours (MPNST) arises from a peripheral nerve or exhibit nerve sheath differentiation on histology. Proximal portions of the upper and lower extremities and the trunk are the most common sites of occurrence. Around 50% are associated with Neurofibromatosis Type 1 (NF1) with incidence of two to five per cent in patients with NF1. The estimated incidence in general population without NF1 is 0.0001% of which gastrointestinal MPNST are extremely rare. A 45-year-old lady without pathological antecedent for NF1 was admitted with pain in right lower abdomen and multiple episodes of vomiting for 3 months. Preoperatively intussusception was diagnosed in the small bowel with USG and CECT abdomen showing characteristic target sign. On laparotomy Ileo-ileal intussusception (proximal ileum telescoping into distal ileum) was found 2 feet proximal to ileo-caecal junction with surrounding inflammed mesentery and presence of intraluminal tumour as lead point. Resection of involved segment of ileum along with its mesentery was done followed by ileo-ileal anastomosis. Histopathology was suggestive of high grade MPNST. Postoperative course and follow up for last 10 month is uneventful. This case is unique in terms of a rare tumour presenting with unusual complication and only one case had been reported so far in western literature. PMID- 26155548 TI - Novel Cytogenetic Aberrations in a Patient of Chronic Myeloid Leukemia with Blast Crisis. AB - Chronic myeloid leukaemia (CML) is a clonal haematological disease which is characterized by a diagnostic karyotypic abnormality t (9;22)(q34;q11) called as Philadelphia (Ph) chromosome. Occurrence of additional chromosomal abnormalities besides the Ph chromosome is defined as clonal evolution (CE) and considered to be a marker of disease progression. A 67-year-old male who was initially evaluated at a private hospital where a diagnosis of acute promyelocytic leukaemia was made on bone marrow aspirate with ambiguous RT-PCR report referred to our centre for further evaluation and treatment. On conventional karyotyping, Ph chromosome along with translocations t(5;13)(q12;p13), t(15;20)(q22;p13) and monosomy 13 was observed in all 20 metaphases. A final diagnosis of CML-myeloid blast crisis with complex cytogenetics was made. Patient succumbed to death within one month of initiation of imatinib therapy. PMID- 26155549 TI - Hyper-fractionated Intensity Modulated Radiation Therapy (HF-IMRT) in Head and Neck Cancer: The Technical Feasibility and Results of a Short Clinical Series. AB - Among various altered fractionation schedules, only hyper-fractionation has proven increased local control in head and neck cancers. MARCH (Metanalyses of Hyperfractionated or Accelerated radiotherapy in Head and neck cancer) concluded that hyper-fractionated radiotherapy in head and cancers had a survival benefit. This study attempts to combine the benefits of hyper-fractionation with the tissue sparing qualities of intensity modulated radiotherapy. Three patients with advanced oro-pharyngeal cancers were treated with HF-IMRT (Hyperfractionated IMRT) (2 oropharynx, 1 hypopharynx). Two phase treatment planning with phase I prescribed to high risk volume (HRV) and intermediate risk volume (IRV), 60Gy in 50 fractions at 1.2Gy per fraction, 2 fractions/day, 6-8 h apart. The low risk volume (LRV) received 55Gy to the 95% volume at 1.1Gy per fraction in the same 50 fractions. In phase II, HRV alone was prescribed 1960cGy in 20 fractions over two weeks. Total dose to HRV was 7960cGy in 7 wk. No concurrent chemotherapy was given. Treatment was completed as planned (<60 days; break of 11 days was due to radiation toxicity). Only one patient had grade III toxicity. All three required diet modifications, an average weight loss of 3 kg and no hospitalization required during treatment. This pilot study shows the feasibility of an effective hyper-fractionation with IMRT for head and neck cancers. A Phase II trial is required to prove its efficacy. PMID- 26155550 TI - Digital Cephalometric Tracings by PRO-CEPH V3 Software for Comparative Analyses of Vertical Dimension in Edentulous Patients. AB - BACKGROUND: Several methods, some physiological, some radiographical and some merely based on experience are taken upon by the practitioner to get him/her close to VDO in the edentulous patients. No single method can however claim to be the perfect answer. Lateral cephalograms have been a standard mode of determining the vertical dimensions in dentate and edentulous patients since the past. Due to unavoidable manual errors, there are chances of variations in the radiographic method too. Advancement in the digital technology has made recording jaw relations faster, simpler and more precise. AIM: This study compared the vertical dimension of occlusion in edentulous patients recorded by using three different physiological methods with the aid of digital cephalometric tracings using indigenously developed PRO-CEPH V3 software. MATERIALS AND METHODS: For the present study a total of 50 dentulous and 25 edentulous patients were selected through inclusion and exclusion criteria. A lateral cephalometric radiograph was taken for all the 50 dentulous subjects at Maximum Intercuspation (VDO) whereas three lateral cephalometric radiographs were obtained for all edentulous patients at the VDO following three different techniques- the Niswonger's method, Phonetics method and Swallowing threshold method. Cephalometric tracings were carried out using indigenously developed PRO-CEPH V3 software. Linear and angular measurement were made and analysed. CONCLUSION: The indigenously developed software PRO-CEPH V3 is capable of making both the linear and angular measurement and therefore provide with relative credibility information regarding the possible VDO in the edentulous patients through cephalometric radiography. PMID- 26155551 TI - Comparative Analysis of Canal Centering Ability of Different Single File Systems Using Cone Beam Computed Tomography- An In-Vitro Study. AB - BACKGROUND: The ability of an endodontic instrument to remain centered in the root canal system is one of the most important characteristic influencing the clinical performance of a particular file system. Thus, it is important to assess the canal centering ability of newly introduced single file systems before they can be considered a viable replacement of full-sequence rotary file systems. AIM: The aim of the study was to compare the canal transportation, centering ability, and time taken for preparation of curved root canals after instrumentation with single file systems One Shape and Wave One, using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Sixty mesiobuccal canals of mandibular molars with an angle of curvature ranging from 20(o) to 35(o) were divided into three groups of 20 samples each: ProTaper PT (group I) - full-sequence rotary control group, OneShape OS (group II)- single file continuous rotation, WaveOne WO - single file reciprocal motion (group III). Pre instrumentation and post instrumentation three dimensional CBCT images were obtained from root cross-sections at 3mm, 6mm and 9mm from the apex. Scanned images were then accessed to determine canal transportation and centering ability. The data collected were evaluated using one way analysis of variance (ANOVA) with Tukey's honestly significant difference test. RESULTS: It was observed that there were no differences in the magnitude of transportation between the rotary instruments (p >0.05) at both 3mm as well as 6mm from the apex. At 9 mm from the apex, Group I PT showed significantly higher mean canal transportation and lower centering ability (0.19+/-0.08 and 0.39+/ 0.16), as compared to Group II OS (0.12+/-0.07 and 0.54+/-0.24) and Group III WO (0.13+/-0.06 and 0.55+/-0.18) while the differences between OS and WO were not statistically significant. CONCLUSION: It was concluded that there was minor difference between the tested groups. Single file systems demonstrated average canal transportation and centering ability comparable to full sequence Protaper system in curved root canals. PMID- 26155552 TI - Effect of Contrast Inversion Enhancement on the Accuracy of Endodontic File Length Determination in Digital Radiography. AB - OBJECTIVE: The aim of this ex vivo study was to evaluate the accuracy of endodontic file length measurement on digital periapical radiographs after application of contrast inversion digital enhancement. MATERIALS AND METHODS: Forty single-rooted single-canal mature permanent human teeth with canals measuring 20-24 mm in length were used in this study. ISO #08 K-files were placed in the root canals of the teeth. The file lengths were measured with a digital caliper as the gold standard. Standard periapical digital images were obtained with the Digora storage phosphor plates and Digora Optime scanner as the original images. The contrast inversion option of Scanora software program version 5.1 was used to produce enhanced images. Three radiologists and three endodontists measured file lengths on the original and enhanced images. The measurements were compared using repeated measures ANOVA and Bonferroni tests (alpha=0.05). RESULTS: There were significant differences between the measurement accuracy of the original and enhanced images (p<0.05). The enhanced images exhibited longer measurements compared to the original images. However, the two sets of digital radiographs provided significantly longer measurements compared to the gold standard (p<0.05). CONCLUSION: The contrast inversion tool of Scanora software program decreases measurement accuracy of the length of small endodontic files on digital periapical radiographs. It is suggested that contrast inversion should not be used in determining the lengths of small endodontic files. PMID- 26155553 TI - Evaluation of Correlation of Blood Glucose and Salivary Glucose Level in Known Diabetic Patients. AB - INTRODUCTION: Diabetes mellitus is a chronic heterogenous disease in which there is dysregulation of carbohydrates, protein and lipid metabolism; leading to elevated blood glucose levels. The present study was conducted to evaluate the correlation between blood glucose and salivary glucose levels in known diabetic patients and control group and also to evaluate salivary glucose level as a diagnostic tool in diabetic patients. MATERIALS AND METHODS: A total number of 250 patients were studied, out of which 212 formed the study group and 38 formed the control group. RESULT: Among 250 patients, correlation was evaluated between blood glucose and salivary glucose values which on analysis revealed Pearson correlation of 0.073. The p-value was 0.247, which was statistically non significant. CONCLUSION: Salivary glucose values cannot be considered as a diagnostic tool for diabetic individuals. PMID- 26155554 TI - Influence of Ultrasonic Irrigation and Chloroform on Cleanliness of Dentinal Tubules During Endodontic Retreatment-An Invitro SEM Study. AB - BACKGROUND: Ultrasonic irrigation has been proved for its remarkable cleaning efficiency in the field of endodontics. But its role in endodontic re-treatment has been understated. There is not much data available to understand the effect of ultrasonic irrigation for the evaluation of cleanliness of dentinal tubules when it is used with or without chloroform, a gutta percha solvent during endodontic retreatment. AIM: To compare the influence of ultrasonic irrigation with syringe irrigation on cleanliness of dentinal tubules after gutta perch removal for endodontic retreatment with or without the use of chloroform a gutta percha solvent using scanning electron microscope (SEM). MATERIALS AND METHODS: Freshly extracted 45 human mandibular premolar teeth for periodontal and orthodontic reasons were taken and were occlusally adjusted to a working length of 19 mm. The root canals of all teeth were prepared chemo mechanically to a master apical file size 40 and were divided in various groups. In Group 1 (n = 5; control group), the canals remained unfilled. In Groups 2 and 3 (n = 20 each), the canals were filled using lateral compaction with gutta-percha and AH plus sealer, removal of root fillings was undertaken after 2 weeks using Gates Glidden drills and H files without chloroform in Group 2 and with chloroform in group 3. The specimen of Group 2 and 3 were further divided into two subgroups I and II (n=10). In subgroup I, irrigation was done using side vented needles and sodium hypochlorite. In subgroup II irrigation was done using passive ultrasonic irrigation with sodium hypochlorite. Thereafter, the roots were split and the sections were observed under SEM. The number of occluded dentinal tubules /total number of dentinal tubules were calculated for the coronal, middle and apical third of each root half. Statistical analysis was performed using one-way ANOVA followed by Tukey's test using standardized technique. RESULT: Results indicated that the cleanest dentinal tubules were found in the control group (Group 1 where the canals were unfilled) followed by the non chloroform group with ultrasonic irrigation (Group 3 subdivision II) followed by chloroform group with ultrasonic irrigation (Group 2 subdivision II), the non chloroform group with syringe irrigation (Group 3 subdivision I) and least cleanliness was found in the chloroform group with syringe irrigation (Group 2 subdivision I). CONCLUSION: Under the limitations of this study it could be concluded that both ultrasonic and syringe irrigation showed cleaner canals when chloroform was not used. Irrigation when done with ultrasonics leads to cleaner tubules than syringe irrigation. Hence, mechanical methods of retrieval in conjunction with use of passive ultrasonic irrigation should be a part of retreatment protocol. PMID- 26155555 TI - In Vivo Autofluorescence Spectroscopic Study and Evaluation of DNA Damage By Comet Assay in Smokers. AB - CONTEXT: Tobacco is known environmental factor to alter the chemical composition of cells and the structure of DNA. Cellular level changes of smoker's mucosa are assessed by autofluorescence spectroscopy and the DNA damage can be evaluated by single cell gel electrophoresis (comet assay). AIM: To substantiate the changes in the autofluorescence due to smoking with that of early DNA damage without any clinical change. MATERIALS AND METHODS: Group I consists of 20 individuals with normal mucosa and Group II consists of 40 individuals with smoking habit. Only males were included in this study and their age ranging from 25 to 35 years. In vivo fluorescence spectra from both groups were obtained by using hand held fiber optic probe attached to Varian Cary Eclipse fluorescence spectrophotometer and comet assay was carried out for normal and smokers by their peripheral blood. STATISTICAL ANALYSIS USED: Independent-Samples t-test was used for statistical analysis. P-value was obtained to discriminate the statistical differences between the two groups. RESULTS: The averaged excitation and emission spectra of normal and smoker's mucosa showed significant differences statistically. In comet assay, the mean tail length of smoker group was higher than the normal group. The results showed statistically significant differences (p <= 0.05). CONCLUSION: These techniques will be very useful for monitoring of very early changes of mucosa before clinical manifestation of the lesion in high risk smokers and thus prevents the occurrence of premalignant disorders and early invasive carcinoma. PMID- 26155556 TI - Expression of Proliferating Cell Nuclear Antigen (PCNA) in Oral Submucous Fibrosis: An Immunohistochemical Study. AB - BACKGROUND AND OBJECTIVES: Expression of Proliferating Cell Nuclear Antigen (PCNA) well-correlates with the cell division. The suprabasal expression of PCNA is considered to be a marker of dysplastic oral mucosa indicating a special proliferative cellular state in those lesions. Oral submucous fibrosis (OSMF) is considered to be a premalignant condition with potential to get transformed into oral squamous cell carcinoma (OSCC). The present study was done to assess the PCNA expression in different grades and in different layers of epithelium of OSMF and to compare the expression of PCNA in OSMF with OSCC. MATERIALS AND METHODS: A group of 40 histopathologically diagnosed, formalin fixed, paraffin embedded tissue samples were included in study. The study group was further divided into 2 groups; 30 OSMF and 10 OSCC. Theses samples were collected from Department of Oral and Maxillofacial Pathology, Government Dental College and Research Institute, Bangalore. The samples were subjected to immunohistochemical method using indirect immunoenzyme LSAB method. RESULTS: All 40 cases showed positivity for PCNA. The percentage of positive cells was more in basal and suprabasal layer both in OSMF and OSCC, whereas the greater percentage of positive cells was seen in the superficial layer of OSCC. All OSMF cases showed positive expression in basal and suprabasal layer and only 77% of cases showed positive PCNA expression in the superficial layer with variable immunoreactivity and 23% did not show any positive staining in the superficial layer. The percentage of positive cells and the intensity of staining increased as the disease severity increased in OSMF. CONCLUSION: Increased proportion of cells expressed PCNA staining which are in proliferative layers of OSMF. This biomarker provides an insight into the biological behaviour of the condition that substantiates its potentially malignant nature and may also provide an intermediate end point in chemotherapeutic trials. PMID- 26155557 TI - Clinical Implications of Preformed Archwire Selection on the Treatment of Angle Class I/II division 1 Malocclusions in Thais. AB - INTRODUCTION: The dental arch forms were compared of untreated Class I and Class II div 1 malocclusions to those of non-customized preformed archwires manufactured by American Orthodontics, G&H, Highland, Ormco, RMO, and 3MUnitek. Arch forms of post-treatment Class II div 1 malocclusions treated by four 1st premolar extractions are also compared. MATERIALS AND METHODS: Four metrics of archform shape and size (canine and 1(st) molar depth and inter-canine and inter 1(st) molar width) were measured on dental casts of 40 Class I and 22 Class II div 1 patients. These same metrics were also used to describe preformed archwire forms. RESULTS: Non-customized preformed wires all showed significantly narrowed mandibular arch forms. This was true for maxillary archwires, with four exceptions. The Highland Natural Arch form, G&H True form I, and RMO natural preformed archwires showed both inter-canine and 1(st) molar widths statistically the same as mean dental arch widths in both the untreated and post-treatment Class II groups. In Class I patients, these three archwires showed only inter canine widths equivalent to dental measurements. The Highland Progressive archwire matched only the 1(st) molar width in the untreated Class II group. CONCLUSION: None of these archwires - if used unadjusted, will produce a significant expansive force in either the maxillary or mandibular arch. Three maxillary non-customized preformed archwires showed both inter-canine and 1(st) molar arch widths statistically the same as Thai Class II div 1 dental arch dimensions. Using them to treat this malocclusion should minimally affect both pre and post-treatment maxillary arch form. PMID- 26155558 TI - A Comparative Evaluation of Shear Bond Strength Between Two Commercially Available Heat Cured Resilient Liners and Denture Base Resin with Different Surface Treatments. AB - BACKGROUND: Soft denture liners are widespread materials used in prosthetic dentistry. Their mechanical properties have to meet several key requirements such as adequate bond to denture base resins in order to provide right function of masticatory system and oral hygiene. AIM: To evaluate and compare the shear bond strength between two commercially available liners and polymethyl methacrylate (PMMA) denture base resin with different surface treatments. MATERIALS AND METHODS: The two soft denture liners - Luci-Sof (silicone based liner) and Super Soft (acrylic based liner) and a polymethyl methacrylate denture base resin (Trevalon) were chosen for the study. A total of 80 samples were made, 40 each for each of the two materials under investigation. The 40 samples were further divided into four groups, containing 10 samples each. Group I: Consisted of an untreated surface of polymethyl methacrylate which acted as the control. Group II: The surface of polymethyl methacrylate surface was sandblasted. Group III: The polymethyl methacrylate surface was treated with monomer. Group IV: The lining material was processed with acrylic resin dough. The samples after thermocycling for 500 cycles with temperatures from 5 degrees +/- 1 degrees C to 55 degrees +/- 1 degrees C and a 60 sec dwell time were subjected to shear loading on universal testing machine at crosshead speed of 20mm/sec. A Scanning Electron Microscope and stereomicroscope analysis of the bond interface between the liner and the denture base was conducted for all the groups of the two materials under study. STATISTICAL ANALYSIS: Data was analyzed using independent samples t-test, analysis of variance (ANOVA) and Post-Hoc Analysis. A significance level of alpha = 0.05 was used for statistical analyses. RESULTS: The bond strength was significantly different between Super- Soft and Luci-Sof (p<0.05) for all surface treatments. The scanning electron microscopy observations showed that the application of surface treatments modified the surface of the denture base resin. CONCLUSIONS: Super-Soft exhibited significantly higher bond strength than Luci-Sof. It was observed that Super-Soft when packed with the pre-polymerized samples produced highest bond strength values among all the groups for both the materials under study. The lowest bond strength was achieved for pre-polymerized samples when packed with Luci-Sof. PMID- 26155559 TI - Reliability of Panoramic Radiographs in the Localization of Mandibular Foramen. AB - OBJECTIVE: The present study evaluated the reliability and accuracy of panoramic radiographs in the localization of mandibular foramen. MATERIALS AND METHODS: Twenty five Indian dry human adult mandibles constituted the study material. Ten measurements were carried on each of them to evaluate the location of mandibular foramen with respect to adjacent anatomic landmarks. Panoramic radiographs were then made of the mandibles. Same distances were measured on the traced images of the radiographs. Paired t-test and Pearson's correlation test were applied to evaluate the accuracy and reliability of panoramic radiographs in localization of mandibular foramen. RESULTS: The mean distances measured on dry mandibles and panoramic radiographs showed statistically significant difference (p<0.05). There was strong positive correlation between the measurements on dry mandible and panoramic radiographs. CONCLUSION: The panoramic radiographs can serve as a guide in locating the anterosuperior point of mandibular foramen on panoramic radiographs. PMID- 26155560 TI - The Association Between Psychological Factors and Orofacial Pain and Its Effect on Quality of Life: A Hospital Based Study. AB - OBJECTIVE: To examine the hypothesis that psychological factors of psychological distress and perception of unhappiness in childhood are associated with self reported orofacial pain and to examine whether such patients have a poorer perception of their oral health related quality of life and if so then to what extent. MATERIALS AND METHODS: A cross-sectional hospital based study was conducted in Hitkarini Dental College and Hospital, Jabalpur amongst 400 cases and 400 controls. Patients were included based on Locker and Slade's criteria. Patients were asked to complete 27 items Questionnaire which included the General Health Questionnaire to assess for psychological distress and Oral Health Impact Profile-14 for evaluating impact on quality of life. Bivariate and logistic regression analyses were performed to determine the degree of association between psychological factors, unhappy childhood and quality of life. P-value of less than 0.05 was considered statistically significant. RESULTS: An increased propensity to report orofacial pain was seen for those individuals with higher levels of Psychological Distress and with perception of Unhappiness in Childhood. These individuals also reported with poorer perception of their oral health related Quality of Life. CONCLUSION: The present study has shown relationship between Orofacial Pain, Quality of Life and Psychological Factors. PMID- 26155561 TI - Does Hollowing of Complete Denture Enhance Retention? - A Pilot Study. AB - INTRODUCTION: Prosthetic rehabilitation is an extremely challenging task in extreme resorption cases of the maxillary denture-bearing area. Reducing the weight of a maxillary obturator has been seen as beneficial. But whether reducing the weight of conventional complete denture also increases retention or not, is still very dubious. The aim of this pilot study was to determine the effect of maxillary denture weight on denture retention and stability. MATERIALS AND METHODS: For this study, a total of 10 patients were considered for the pilot study (06 female and 04 male) with an average age of 70 y. Each patient was provided with two sets of maxillary complete dentures, one hollow labeled as A and one conventional maxillary denture labeled as B. RESULTS: It was shown that mean values for retention using MKIS for retention for hollow dentures (A) was 7.8 and for conventional dentures (B) it was 8.2 and the stability for maxillary dentures was more with conventional dentures (B) than hollow maxillary dentures (A) and it was significant as p-value was 0.015 (p<.1). CONCLUSION: The denture retention and stability, chewing and comfort values of conventional dentures and hollow dentures were slightly better for conventional dentures. PMID- 26155562 TI - Association Between Gingival Crevicular Fluid Leptin Levels and Periodontal Status - A Biochemical Study on Indian Patients. AB - AIM: The present study was carried out to evaluate and compare the gingival crevicular fluid (GCF) concentrations of leptin in periodontally healthy and diseased subjects, to compare GCF leptin levels with respect to Body Mass Index (BMI) among the study groups and essentially to obtain an insight into leptin's possible role in the initiation and progression of periodontal disease. MATERIALS AND METHODS: A total of 60 subjects; both males and females, based on their body mass index were selected for the study. They were categorized into three groups of 20 subjects each, based on their periodontal status, as follows: Group I (clinically healthy periodontium); Group II (gingivitis); Group III (chronic periodontitis). GCF samples of 1 MUl were collected extra-crevicularly using black color-coded 1-5 MUl calibrated volumetric microcapillary pipettes from one site in each person, and samples were analyzed for leptin using a commercially available ELISA kit. RESULTS: The concentration of leptin in GCF of patients in Group I (2272.25 pg/mL) was statistically higher (p < 0.001) than in those of Group II (1421.86 pg/mL) and Group III (1160.67 pg/mL). No statistically significant difference was found when comparing the mean values of leptin between BMI groups in each study group. CONCLUSION: As periodontal disease progressed, there was a substantial decrease in the gingival crevicular fluid leptin concentration. This suggests a protective role of leptin with regard to periodontal health. PMID- 26155563 TI - Quantitative Assessment of Calcium Profile in Whole Saliva From Smokers and Non Smokers with Chronic Generalized Periodontitis. AB - BACKGROUND: Measures of in vivo calcium status are important in understanding the mineralization capacity as it is an essential mineral component of both teeth and bone; and also play a vital role in the lipid profile and hormonal balance. AIM: To evaluate the existence of any disturbances in calcium metabolism and absorption induced by smoking, by quantitatively assessing the variations in the salivary calcium level between smokers and non-smokers with periodontitis and relating to their periodontal status. MATERIALS AND METHODS: A total of 50 male patients were selected and categorized as Group I (smokers with chronic generalized periodontitis) and Group II (non-smoker/ non-tobacco users with chronic generalized periodontitis). Clinical parameters such as Calculus Index and Community Periodontal Index were assessed. Subsequently two ml of unstimulated whole saliva was collected and subjected to biochemical analysis for the estimation of salivary calcium which was carried out in the next 20 min. RESULTS: Salivary calcium levels were significantly higher in Group I (2.2700) compared to Group II (1.7260). Higher calculus index and CPI index score were also seen in Group I when compared to Group II. CONCLUSION: Elevated salivary calcium level among the Group I emphasize the decreased calcium absorption efficiency among the smokers. High salivary calcium content hardens plaque more rapidly, indirectly influencing the level of oral hygiene. PMID- 26155564 TI - Evaluation of Oral Changes Among Tobacco Users of Aljouf Province, Saudi Arabia. AB - OBJECTIVE: To know the prevalence of tobacco associated changes among male population of Aljouf province of Saudi Arabia. MATERIALS AND METHODS: This study included 536 male subjects with positive history of tobacco habits. All the participants were asked to fill a questionnaire regarding the habit details and were examined clinically for the oral changes. RESULTS: Majority of the subjects used tobacco in smoked form (69.0%). Out of the 536 patients with tobacco smoking and chewing habits 72% showed changes in oral mucosa. Smokers melanosis (43.28%) was the most commonly observed oral change followed by leukoedema (27.05%) and smoker's palate (22.76%). Leukoplakia (3.17%) was the most commonly seen premalignant lesion. CONCLUSION: The study confirms the fact that use of tobacco can be positively correlated to the occurrence of various benign, premalignant and malignant oral changes. This study aids in creating awareness among the public regarding the deleterious effects of tobacco and may motivate them for cessation of tobacco use. PMID- 26155565 TI - Ergonomic Microscope: Need of the Hour. AB - BACKGROUND: Prolonged use of conventional microscope develops musculo-skeletal injuries like chronic pain syndrome, including shoulder, neck, back aches & fatigue. Since the problems go unnoticed, the injuries can lead to some serious permanent damages. This further leads to a compromise in the health and welfare of the person and the institute. Hence, an understanding about the ergonomics is the need of the hour in this postmodern era. Inspite of few studies and surveys about ergonomics, there is still a steep rise in the musculoskeletal disorders. AIM OF THE STUDY: The aim of our study was to gauge the general awareness of pathologists, microbiologists and oral pathologists towards ergonomics in their profession. MATERIALS AND METHODS: A cross-sectional survey based study was de signed, which included a questionnaire. The questionnaire included multiple choice questions with four alternatives. Professionals (pathologists, microbiologists and oral pathologists) were included in the survey. Teaching faculty (Professors, Associate Professors and Lecturers) and Post graduate students formed the study group. RESULTS AND OBSERVATIONS: The response to the questionnaire was 100%. Less than 50% of oral pathologists were aware of the importance of ergonomics in their profession. The most common site affected was neck and back. One of the drastic observations was that, Oral Pathologists suffered from a combination of problems affecting neck, back, eyes, headache, shoulders, arms and wrists. CONCLUSION: Increase in our understanding regarding ergonomic-ally designed microscopes can increase our efficiency and in turn improve our general well-being. With improvements in ergonomics, professionals would be able to modify and optimize their working conditions. Certain guidelines need to be followed by the profes-sionals to reduce chances of musculoskeletal disorders. PMID- 26155566 TI - Gingival Biotype Assessment in a Healthy Periodontium: Transgingival Probing Method. AB - BACKGROUND: Gingival biotype is the thickness of the gingiva in the faciopalatal dimension. It has a significant impact on the outcome of the restorative, regenerative and implant therapy. It has been suggested that a direct co-relation exists with the susceptibility of gingival recession followed by any surgical procedure. So, the study was aimed to assess gingival biotype in different age groups of males and females using transgingival probing method. MATERIALS AND METHODS: Gingival thickness (GT) was evaluated in 336 patients including males and females of different age groups. The latter was based on the transparency of the periodontal probe through the gingival margin while probing the buccal sulcus. Final data collected was then used for statistical analysis. RESULTS: A significant difference was found between males and females with males showing thick biotype. Out of the total samples 76.9% of males showed thick biotype compared to 13.3 % of females which was statistically significant. CONCLUSION: This was probably one of the few attempts to correlate gingival biotype with different age groups in males and females. A clear thick gingiva was found in more than two-third of the male subjects whereas majority of female subjects showed thin biotype. Also, it was seen that in females, the gingival biotype varies with age unlike in male. PMID- 26155567 TI - Adjunctive Effects of A Piscean Collagen-Based Controlled-Release Chlorhexidine Chip in the Treatment of Chronic Periodontitis: A Clinical and Microbiological Study. AB - INTRODUCTION: PerioChip a bovine origin gelatine based CHX chip has shown beneficial effects in the management of Chronic Periodontitis. A new fish collagen based CHX chip similar to PerioChip is currently available; however this product has not been thoroughly researched. AIM: The aim of the present study was to evaluate the effectiveness of a new Piscean collagen-based controlled-release chlorhexidine chip (CHX chip) as an adjunctive therapy to scaling and root planing (SRP). SETTINGS AND DESIGN: The study was conducted as a randomised, split-mouth, controlled clinical trial at Krishnadevaraya College of Dental Sciences, Bangalore, India. MATERIALS AND METHODS: In a split-mouth study involving 20 sites in 10 patients with chronic periodontitis, control sites received scaling and root planing and test sites received scaling and root planing (SRP) and the intrapocket CHX chip placement as an adjunct. Subgingival plaque samples were collected from both control and test sites at baseline, 11 days and 11 weeks and the anaerobic colony count were assessed. Clinical parameters that were recorded at baseline and 11 weeks were gingival index, Plaque index, Probing pocket depth (PPD), and Clinical attachment level (CAL). Plaque index was recorded additionally at 11 days. RESULTS: In the test group there was a statistically significant reduction in the total anaerobic colony count, gingival index and plaque scores from baseline as compared to control sites at all time intervals. An additional 0.8mm reduction in mean probing pocket depth was noted in the test group. Gain in Clinical attachment level was comparable in both groups. CONCLUSION: The adjunctive use of the new collagen based CHX chip yielded significant antimicrobial benefit accompanied by a reduction in probing depth and a clinical attachment level gain as compared to SRP alone. This suggests that it may be a useful treatment option of nonsurgical periodontal treatment of chronic periodontitis. PMID- 26155568 TI - Effect of Peracetic Acid as A Final Rinse on Push Out Bond Strength of Root Canal Sealers to Root Dentin. AB - BACKGROUND: Smear layer which was formed during the instrumentation of root canals hinders the penetration of root canal sealers to root dentin and affect the bond strength of root canal sealers to root dentin. Final irrigant such as demineralizing agents are used to remove the inorganic portion of the smear layer. In the present study, peracetic acid used as a final rinse, to effect the bond strength of root canal sealers to root dentin. AIM: The purpose of the present study was to evaluate the efficacy of peracetic acid as a final irrigant on bond strength of root canal sealers to root dentin. MATERIALS AND METHODS: Sixty six freshly extracted human single rooted mandibular premolars were used for this study. After decoronation the samples were instrumented with Protaper upto F3 and irrigated with 5.25% NaOcl. The teeth were then divided into three groups based on final irrigant used: Group-1(control group) Canals were irrigated with distilled water. Group-2: Canals were irrigated with peracetic acid. Group 3: Canals were irrigated with smear clear. Each group was further divided into three subgroups (n=30) based on the sealer used to obturate the canals. Subgroup 1: kerr, Subgroup-2: Apexit plus, Subgroup-3: AH PLUS. Each sealer was mixed and coated to master cone and placed in the canal. The bonding between sealer and dentin surface was evaluated using push out bond strength by universal testing machine. The mean bond strength values of each group were statistically evaluated using Two-way ANOVA followed by Tukey post-hoc test. RESULTS: Significant difference was found among the bond strength of the sealers. But, there is no statistically significant difference between the groups irrigated with peracetic acid and smear clear compared to control group. AH Plus showed highest bond strength irrespective of the final irrigant used. CONCLUSION: Peracetic acid when employed as final irrigant improved the bond strength of root canal sealers compared to control group but not statistically significant than smear clear. PMID- 26155569 TI - An In-Vitro Comparison of Micro Leakage Between Two Posterior Composites Restored with Different Layering Techniques Using Two Different LED Modes. AB - AIM: Composite resins have undergone various advances since their introduction, but their polymerization shrinkage remains a problem. Shrinkage can cause debonding of the restoration and can contribute to postoperative sensitivity, secondary caries, marginal staining and eventual failure of the restoration. So, our aim is to compare the effect of two different placement techniques and two different curing modes in reducing the marginal microleakage of two different composites in Class II cavities, where oblique and horizontal placement techniques and ramp & pulse curing modes of LED are used during the restoration. MATERIALS AND METHODS: Standardized slot preparations were prepared in 80 human multi-rooted teeth. The teeth were randomly divided into four groups. Group A and B: Restored with Filtek P60 (3M, ESPE), Group C and D: Restored with Filtek P90 (3M, ESPE). All groups were further divided into sub-groups on basis of placement technique and curing mode. The samples were stored in distilled water, followed by thermocycling and immersed in 2% methylene blue. The samples were sectioned and evaluated for microleakage at the gingival margin with an optical stereomicroscope. RESULTS: P60 composite when placed in the cavity with oblique incremental technique and cured with ramp mode of LED showed highest mean microleakage. There is no significant difference between horizontal and oblique placement technique (p=0.80); Pulse-curing and the ramp-curing mode (p=0.62). CONCLUSION: In restoring deep class II cavities, the use of a low-shrink composite with the oblique placement technique and ramp curing mode of LED is recommended to overcome the problem of marginal microleakage. PMID- 26155570 TI - The Attitudes of Dentists Towards the Prescription of Antibiotics During Endodontic Treatment in North of Saudi Arabia. AB - OBJECTIVE: The use of antimicrobial agents has been increased, leading to bacterial resistance. Therefore the health professionals should have a sound knowledge about the prescription of antibiotics to overcome the increasing bacterial resistance. The main objective of this study was to evaluate the attitudes of dentists towards the prescription of antibiotics during endodontic treatment in north of Saudi Arabia. MATERIALS AND METHODS: This was a survey based descriptive cross-sectional study. This study has been done among the dentists of northern region of Saudi Arabia. A questionnaire was designed, regarding pattern of prescription of antibiotics by the dentists in the north of Saudi Arabia and the use of antibiotics in the treatment of different endodontic conditions during endodontic treatment. This questionnaire was distributed among 200 dentists in the north of Saudi Arabia. This study will encourage the dentists of the northern region of Saudi Arabia to be up to date about the current and prospective guidelines for the prescription of antibiotics and follow these guidelines for the antibiotic prescription. RESULTS: The collected information was analysed by using a computer software SPSS version 18. Majority of the dentists were male accounting for 86%. The age range for 68% of the respondents was 25-35 years. Most of the dentists were having just a basic dental qualification i.e. 65.60%. Out of the total responding dentists, 50% were working in the ministry of health. 77% of the respondents prescribed the antibiotics for necrotic pulp with acute apical periodontitis; swelling present; mod/ severe preoperative symptoms. Out of the total responding dentists, 45.2% prescribed amoxicillin and clavulanic acid combination as the drug of choice. CONCLUSION: It is concluded from the present study that the dentists should know the scientific basis for the prescription of antibiotics during endodontic therapy. They should follow and should not neglect the current guidelines for antibiotic prescriptions. There should be community awareness programmes for the dentists regarding the misuse of antibiotics and antibiotic resistance so that they can play a role in controlling these global problems. PMID- 26155571 TI - Comparative Effects of Clonidine and Adrenaline with Lignocaine during Maxillary Infiltration Anaesthesia for Dental Extraction. AB - INTRODUCTION: Lignocaine is a commonly used local anaesthetic in dental practice. Many practitioners use adrenaline (epinephrine) as additive with lignocaine, and some have used clonidine, instead of adrenaline. Both having benefits and limitations. AIMS: Hence a study was undertaken in our department to evaluate the advantages and disadvantages of using (plain lidocaine local anaesthetic) versus (lidocaine with adrenaline as additive) versus (lidocaine with clonidine as additive). STUDY DESIGN: Randomised, prospective, double blind study. MATERIALS AND METHODS: Seventy five patients requiring extraction of maxillary molar teeth who fall under ASA I category were included and randomly divided into group - I (n=25) (Lignocaine), group - II (n=25) (Lignocaine +/- Adrenaline) and group - III (n=25) (Lignocaine +/- Clonidine). The observations recorded were, time of onset of anaesthesia, hemodynamic parameters, blood loss during procedure and duration of post operative analgesia. STATISTICAL ANALYSIS: The statistical analysis was carried out using SPSS 16 software. RESULTS: A statistically significant difference was seen in blood loss, being higher in group I and duration of anaesthesia, being shortest in group I. There was no statistical difference between the three groups amongst other parameters. CONCLUSION: Adrenaline at 10 MUg/ml and clonidine at 15 MUg/ml can be safely used as additives with lignocaine, in maxillary infiltration anaesthesia for dental extraction; with addition of either of these two drugs, having an equal advantage over use of plain lignocaine; in terms of lower blood loss and longer duration of anaesthesia; but, with no difference in the onset of anaesthesia and with no significant hemodynamic changes. PMID- 26155572 TI - Estimation of Salivary Glucose and Glycogen Content in Exfoliated Buccal Mucosal Cells of Patients with Type II Diabetes Mellitus. AB - BACKGROUND: Diabetes mellitus is a common metabolic disorder which shows an increasing incidence worldwide. Constant monitoring of blood glucose in diabetic patient is required which involves painful invasive techniques. Saliva is gaining acceptance as diagnostic tool for various systemic diseases which can be collected noninvasively and by individuals with limited training. AIM: The aim of the present study was to analyse the possibility of using salivary glucose and glycogen content of buccal mucosal cells as a diagnostic marker in Type II Diabetes mellitus patients which can be considered as adjuvant diagnostic tool to the gold standards. MATERIALS AND METHODS: Sample consists of 30 study and 30 control groups. Saliva was collected by passive drool method.Intravenous blood samples were collected for glucose estimation. Exfoliated buccal mucosal cells were collected from apparently normal buccal mucosa, smeared on dry glass slide and stained with PAS. Blood and salivary glucose are estimated by Glucose Oxidase endpoint method. For Glycogen estimation, number of PAS positive cells in fifty unfolded cells was analysed. RESULTS: The results of the present study revealed a significant increase in the salivary glucose level and the number of PAS positive buccal mucosal cells in the diabetics than in the controls. The correlation between the fasting serum glucose and fasting salivary glucose and also that between fasting serum glucose and PAS positive cells was statistically significant. But the correlation between the staining intensity and fasting serum glucose was statistically insignificant. CONCLUSION: With the results of the present study it is revealed that salivary glucose and PAS positive cells are increased in diabetics which can be considered as adjuvant diagnostic tool for Diabetes mellitus. PMID- 26155573 TI - Toothbrush Handles Individually Adapted for Use by Elderly Patients to Reduce Biofilm on Complete Dentures: A Pilot Study. AB - INTRODUCTION: Reduction of biofilm on dentures is important for maintaining denture wearers' health. OBJECTIVE: The aim of this study was to assess the effectiveness of toothbrush handles individually adapted in reducing of biofilm on dentures. MATERIALS AND METHODS: Study participants were 16 residents of the condo for the elderly, denture wearers, functionally independent and without cognitive impairment. Participants were randomly divided into two groups: Group 1 (adapted toothbrush handles) and Group 2 (conventional toothbrush). Biofilm from the inner surface of the basal area of the denture was observed using 5% erythrosine. Images obtained before starting the use of toothbrushes, after 7 and 21 days were sent for computer analysis. RESULTS: The average amount of biofilm on the first day was considered severe in both groups. At the end of the experiment, the average biofilm coverage in Group 1 was 44.7% (13.1% reduction) and in Group 2 it was 48.6% (4.8% reduction). However, the Friedman analysis of variance test showed that the reduction was statistically significant (p< 0.05) only in Group 1, demonstrating the effectiveness of the adapted brushes. CONCLUSION: The findings of this pilot study indicated that for the reduction of biofilm on dentures the adapted toothbrush handles were superior to the conventional type. PMID- 26155574 TI - Comparative Evaluation of Marginal Discrepancy in Tooth Colored Self Cure Acrylic Provisional Restorations With and Without Reinforcement of Glass Beads: An In Vitro Study. AB - CONTEXT: This invitro study was conducted to compare and evaluate marginal discrepancy in two types of tooth colored self cure provisional restorative materials {DPI&UNIFAST TRAD} before and after reinforcement of glass beads. AIM: The aim of the present study was to evaluate and compare marginal discrepancy in two types of provisional restorative materials (DPI and UNI FAST TRAD) before and after reinforcement with Glass beads. MATERIALS AND METHODS: Tooth shaped resin copings were fabricated on custom made brass metal die. A total of 60 resin copings were fabricated in which 30 samples were prepared with DPI and 30 samples with UNIFAST material. Each group of 30 samples were divided in to two sub groups in which 15 samples were prepared with glass bead reinforcement and 15 samples without reinforcement. The marginal discrepancy was evaluated with photomicroscope {Reichet Polyvar 2 met} by placing the resin copings on custom made brass resin coping holder. RESULTS: Measurements obtained were statistically analysed by unpaired t-test to know any significance between two variables. Unreinforced DPI specimens had shown lower marginal discrepancy (442.82) than reinforced specimens (585.77). Unreinforced UNIFAST specimens have shown high values of marginal discrepancy (592.83) than reinforced specimens (436.35). p value between reinforced and unreinforced specimens of DPI (p=0.0013) and UNIFAST (p= 0.0038) has shown statistical significance. CONCLUSION: This in-vitro study revealed that unreinforced DPI specimens have shown lower marginal discrepancy than reinforced specimens and unreinforced UNIFAST specimens have shown higher values of marginal discrepancy than reinforced specimens. PMID- 26155575 TI - Dentigerous Cyst Associated with Adenomatoid Odontogenic Tumour. AB - Adenomatoid odontogenic tumour (AOT), a tumour composed of odontogenic epithelium, is an uncommon tumour of odontogenic origin that accounts for only 2.2- 7.1% of all odontogenic tumours. Very few cases of AOT associated with Dentigerous cyst (DC) have been reported till date, most cases are in females and have a striking tendency to occur in the anterior maxilla. The present case is that of a 14-year-old female who revealed a large radiolucent lesion associated with the crown of an unerupted canine located in the left maxillary anterior region. The microscopic examination revealed the presence of AOT in the fibrous capsule of a DC. In this paper, we describe the importance of grossing, sectioning and complete examination of the slide to diagnose such hybrid lesions. PMID- 26155576 TI - Gingival Fibromatosis with Distinctive Facies - A Three Generation Case Report. AB - Hereditary gingival fibromatosis (HGF) is a rare disorder characterized by progressive and varying degrees of gingival overgrowth. Oral manifestations may vary from minimal involvement of only tuberosity area and the buccal gingiva around the lower molars to a generalized gingival enlargement. It can occur as an isolated disorder but can be one feature of a syndrome. Although the clinical and histopathological characteristics of HGF are well known and described, the pathogenic mechanism remains unknown. The goal of this article is to describe a family with three generations afflicted with a syndromic form of HGF known as gingival fibromatosis with distinctive facies, and discuss the diagnosis and treatment of the disease. PMID- 26155577 TI - Hemangiomatous Ameloblastoma- A Case Report of a Very Rare Variant of Ameloblastoma. AB - Ameloblastoma is a true benign odontogenic neoplasm with many classical histological variants, common being follicular and plexiform types. Hemangiomatous amelobalstoma is a very rare variant that shows unique histopathologic characteristics varying from conventional ameloblastoma. We present a rare variant of ameloblastoma in a 35-year-old female patient with a swelling over left mandibular region, showing mixed radiolucent-opacity, which on enucleation histopathologically revealed ameloblastomatous areas with extensive vascular component. PMID- 26155578 TI - Frog Appliance- An Innovative Treatment Option for the Replacement of Missing Teeth in An Epileptic Child. AB - Epilepsy is a chronic neurological disease which may result in various oro-facial injuries among which fracture of crown and avulsion of tooth are commonly reported. Challenges come in growing epileptic children where fixed prosthesis could not be delivered and it demands a fixed semi-permanent prosthesis that needs strength along with esthetics. The present paper reports an innovative appliance which has fulfilled fore mentioned criteria; with the appliance named frog appliance. PMID- 26155579 TI - Aesthetic Rehabilitation of Subgingival Fractures with Forced Eruption: Case Reports. AB - Aesthetic rehabilitation of sub-gingival crown fractures of the maxillary anterior tooth present extreme challenges to the dental surgeon. The prognosis of traumatized tooth depends on accurate diagnosis and physiological status of the involved tooth. This paper discusses two different cases of subgingival fracture of maxillary anterior tooth that was managed by two different technique of forced eruption. After endodontic management and forced eruption, esthetic rehabilitation was completed by placing post and core, and all ceramic crown. The final result was successful and resulted in good esthetics and secured periodontal health. PMID- 26155580 TI - Complete Denture in a Microstomia Patient. AB - Microstomia is the term used to describe a condition of reduction in the size of oral aperture which can be either acquired or congenital and affects the quality of life. Dentists occasionally come across patients with constricted oral openings. Limited oral opening makes access to the oral cavity for any dental procedure difficult. It's the duty of a dentist to provide every possible care to the patient with microstomia. This paper describes the treatment of a microstomia patient requiring complete dentures using sectional dentures. The cause of microstomia in the indexed patient was developmental in nature as all other causes of related conditions were ruled out. Finally upper and lower complete denture with sectional components were given to the patient after modification in conventional steps of its construction. PMID- 26155581 TI - Sarcomatoid Carcinoma of Anterior Maxilla: A Case Report and Immunohistochemical Analysis. AB - Sarcomatoid carcinoma is a rare and peculiar biphasic malignant neoplasm that occurs mainly in the upper aerodigestive tract. Sarcomatoid carcinoma is an unusual biphasic tumor composed of both malignant epithelial and malignant mesesnchymal component in association with, and usually dominated by, an abundant dysplastic-appearing spindle cells. This tumor consistently poses a significant diagnostic challenge to pathologists. Despite of several immunohistochemical, electron microscopic and genetic studies, precise histogenesis of sarcomatoid carcinoma is quite controversial. Here we are describing a case of sarcomatoid carcinoma in a 40 yr old male patient with special emphasis on immunohistochemical analysis. Here, we are describing a case of sarcomatoid carcinoma in a 40-year-old male who presented with a small swelling & pain in hard palate along with immunohistochemical analysis. PMID- 26155582 TI - Nasopalatine Duct Cyst Associated with a Mesiodens: Misdiagnosis or Missed Diagnosis? AB - Nasopalatine duct cyst ( NPDC) is described as most common non-odontogenic developmental cyst of the jaws. Despite being common, its clinical and radiographic presentation could be varied and it can sometimes be a diagnostic challenge. This paper presents an unusual case of an infected NPDC associated with an impacted inverted mesiodens and a history of trauma that misled the clinical diagnosis. PMID- 26155583 TI - Papillon-Lefevre Syndrome In An Adolescent Female: A Case Study. AB - Papillon-Lefevre Syndrome (PLS) is a rare inherited autosomal-recessive condition with one-third of the patients' showing consanguinity of the parents. Lesions are characterised by palmar-plantar hyperkeratosis and hyperhidrosis. Early onset of periodonditis, severe periodontal destruction in both primary and permanent dentitions, and calcification of the duramater form the three important features of this disease. Here, we present a case of a 14-year-old female who presented to the Department of Oral Medicine and Radiology with a complaint of mobility of the teeth since four months. Oral examination of the patient showed generalised mobility of the teeth. General physical examination of the patient showed dry scaly skin on dorsum of bilateral feet, hands, and knee. The patient had familial history positive for consanguinity. The patient was medically diagnosed as positive for PLS. The patients with PLS show combination of dermatological and dental lesions and it requires the dentist to assume a more prominent role in early treatment and rehabilitation. There is a need for symbiotic and synergetic approach between the two specialties for effective management of this rare disease. PMID- 26155584 TI - Novel Use of PRF and PDT in the Management of Trauma Induced Root Resorption and Infrabony Defect. AB - Root resorption is a common squeal of traumatic injury to the dentition. Its progression can be minimized by early diagnosis and appropriate treatment. This case report presents the diagnosis and management of a case of trauma induced trio of apical root resorption, intraradicular root resorption and infrabony defect in maxillary central incisor. The main aim in treating such cases of resorption is to limit the inflammatory response at the periapical region so as to halt the resorptive process. To allow faster regeneration of the periodontal tissues, Platelet rich fibrin (PRF), a second generation platelet concentrate was used as an apical matrix over which MTA plug was given. The periodontal defect was managed with the help of localized antimicrobial photodynamic therapy (aPDT). PMID- 26155585 TI - Odontogenic Myxoma of the Maxilla- A Rare case Report. AB - Odontogenic myxoma (OM) is an uncommon, benign, locally invasive, non metastasizing neoplasm arising from the odontogenic ectomesenchyme that usually occurs in the tooth bearing areas of the jaws. These lesions arouse special interest as they pose high diagnostic challenge. Here, we present a rare case of OM of the maxilla in an 18-year-old male. The clinical, radiographic and histopathological features of the lesion are discussed in this paper. PMID- 26155586 TI - Peripheral Primitive Neuroectodermal Tumour of the Maxilla and Paranasal Sinuses: A Rare Clinical Presentation. AB - Peripheral Primitive Neuroectodermal Tumours (pPNET) are rare aggressive tumours of neural crest cell origin. These tumours are more common in children and young adults. This is a unique report of one such presentation in a 23-year-old lady occurring in the left side posterior maxilla and Paranasal sinuses along with imaging characteristics, histopathologic features, immunohistochemical aspects and management. Though these tumours are rare, they should be considered in the differential diagnosis of rapidly growing soft tissue masses in young adults. Precise diagnosis with timely management is necessary for good prognosis. PMID- 26155587 TI - Multidisciplinary Management of An Unusual Isolated Alveolar Bone Infection- A Rare Case Report. AB - Restoration of proximal defect of tooth is of paramount importance as its improper restoration usually results in fracture of the restoration or deteriorated periodontal health. The article reports a case with a discreet mass of alveolar bone necrosis closed to the overhanged amalgam restoration in the proximal box of the maxillary molar. As a result of this improper proximal restoration it led to deep periodontal pocket and subsequent alveolar bone necrosis which was managed successfully with combined Endodontic-Periodontic treatment. This article highlights the unfortunate sequelae of bone necrosis as a consequence of an incorrect or overlooked dental treatment and its comprehensive management. PMID- 26155588 TI - Management of A Rare Case of Communicating Internal-External Inflammatory Resorption. AB - The present case describes the successful management of a rare case of communicating internal-external resorption in which both internal and external resorption seem to develop independent of each other. The case report highlights the importance of correct diagnosis and need of revision of classification system of resorptive defects. PMID- 26155589 TI - Multidisciplinary Approach in Management of a Large Cystic Lesion in Anterior Maxilla - A Case Report. AB - Management of large cystic lesion requires a multidisciplinary approach. In this case report a large radicular cyst is managed by conventional root canal treatment with triple antibiotic paste followed by surgical enucleation. In this case, patient presented with a 4 cm symptomatic swelling of the palate adjacent to teeth 21, 22 and 23. The swelling was soft on palpation and the overlying mucosa was of normal color. Radiographically, a well-defined unilocular radiolucency with corticated margins was seen. A full-thickness flap was reflected and revealed a large cyst-like lesion that had perforated the lingual cortical plate. The lesion was enucleated and submitted for microscopic examination. The biopsy report confirmed the diagnosis as radicular cyst.The patient was recalled after 6 months, and no symptoms or signs were noted. Radiograph showed the healing lesion. PMID- 26155590 TI - Hyperbaric Oxygen Therapy-A Novel Treatment Modality in Oral Submucous Fibrosis: A Review. AB - Oral submucous fibrosis (OSMF) is a chronic, debilitating disease characterized by juxta epithelial fibrosis of the oral cavity and regarded as a potentially malignant disorder. Numerous treatment modalities ranging from various drugs to behavioral therapy have been tried with inconsistent results with varying degrees of success reflecting low predictability, requiring further evaluation and standardization. Novel treatment modality such as Hyperbaric oxygen therapy (HBOT) involves inhalation of 100% oxygen at increased atmospheric pressure usually ranging between 2.0 and 2.5 atmospheres for periods between 60 and 120 min. HBOT which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve hypoxic environment of OSMF and also possesses potent anti-inflammatory properties. This article enlightens on possible beneficial effects of HBOT in the management of OSMF at cellular and molecular level. PMID- 26155591 TI - Expression and Significance of Cadherins and Its Subtypes in Development and Progression of Oral Cancers: A Review. AB - Cadherins are a family of transmembranous glycoproteins responsible for calcium dependent intercellular adhesion. Absence or loss of function of E-cadherin leads to the disappearance of epithelial characteristics of the cells and generates higher invasiveness for extracellular matrices. That is why cadherin expression is considered to be a decisive indicator for differentiation, aggressive behaviour, high proliferation, metastasis, poor prognosis and invasiveness of human carcinoma cells. In this review, the role of cadherin expression was focused on, both in development and carcinogenesis, paying particular attention to mechanisms involved in its down-regulation. The elements common to this process in both physiological and pathological situations was analysed, particularly in relation to one of the most common malignancy, oral squamous cell carcinoma. PMID- 26155592 TI - Approaches to Arresting Dental Caries: An Update. AB - BACKGROUND: Dental caries is one of the most prevalent chronic oral diseases across the globe that can be both treated and prevented. Preventive management strategies can effectively arrest and even completely reverse the caries process. This article aimed to review the literature on different approaches explored towards arresting caries progression. MATERIALS AND METHODS: Literature search of publications in Pubmed/Medline was carried out. Total 73 articles including clinical trials, invitro studies, case reports and review articles were reviewed. RESULTS: Twenty-two clinical trials and invitro studies were selected for review. Most studies suggested use of Silver Diamine Fluoride (SDF) as simple and effective caries arresting approach. Fluoride varnish treatment effectively arrests caries by inhibiting demineralization, resulting in highly significant caries reductions. Arginine with an insoluble calcium compound enhances arresting and reversing buccal, coronal and root caries. A few clinical studies have shown that sealants placed in caries fissures can arrest the caries process. CONCLUSION: Various fluoride containing agents are clinically effective in arresting progression of carious lesion. However, these materials should be used appropriately understanding their scope and limitations to arrest dental caries. PMID- 26155594 TI - Ghent Criteria an Aid to Diagnose Latent Systemic Diseases in Marfan Syndrome. PMID- 26155593 TI - Antioxidants in Endodontics: A Strategic Review. AB - Over the past few decades, the free radicals and antioxidants have attracted tremendous importance in the field of dentistry. Depending on the level of free radicals in the body, they can either be harmful or helpful. Antioxidants are the substances that interact with and stabilize free radicals thereby protecting cells from the damage caused by free radicals. The indigenous antioxidants may be useful in preventing the harmful effects of oxidative stress. The present article presents a review on the free radicals formation, their role in disease pathogenesis, antioxidants and their potential role in endodontics. PMID- 26155595 TI - Achondropasia and Dentigerous Cyst- A Coincidental Finding or any Relationship? PMID- 26155596 TI - Effects of Ramadan fasting on glucose homeostasis and adiponectin levels in healthy adult males. AB - BACKGROUND: Adiponectin is a hormone secreted by adipocytes during the fasting phase of the fast-fed cycle. Ramadan fasting involves prolonged fasting for up to twelve hours and thus could lead to increased secretion of adiponectin by adipocytes. However, studies on the role of adiponectin on glucose and body weight homeostasis during Ramadan fasting is still a matter of controversy. Thus the specific aim of this study was to assess the effect of fasting during Ramadan on the adiponectin levels, body weight and glucose homeostasis in healthy male Malaysian subjects. METHODS: Twenty healthy male (19-23 years) Muslim subjects were followed up during the fasting month of Ramadan. Anthropometry and blood samples were taken one week before and during the fourth week of fasting. Plasma glucose, insulin and adiponectin were estimated and insulin sensitivity indices were estimated using the Homeostasis Model Assessment. RESULTS: Subjects experienced a significant decrease in body weight (2.4 %, p < 0.001) and body mass index (5.5 %, p < 0.01). There was also a significant decrease of 12.3 %, 52.8 % and 45.6 % of plasma glucose, insulin and adiponectin respectively (p < 0.01). The drop in adiponectin was positively correlated with the decrease in body weight (r = 0.45, p < 0.05). There was also a significant increase in insulin sensitivity and a decrease in insulin resistance (p < 0.01). CONCLUSIONS: These results indicate that Ramadan fasting in young healthy individuals has a positive impact on the maintenance of glucose homeostasis. It also shows that adiponectin levels dropped along with significant loss in weight. We feel caloric restriction during the Ramadan fasting is in itself sufficient to improve insulin sensitivity in healthy individuals. PMID- 26155598 TI - [Prim. Dr. Vladimir Dugacki (26 February 1939 - 11 March 2014)]. PMID- 26155599 TI - WILDERNESS. PMID- 26155600 TI - QUALITY OF LIFE, CITIZENSHIP, AND NEW FORMS OF POWER IN THE GLOBAL ERA. PMID- 26155597 TI - Risk of HIV-1 acquisition among women who use diff erent types of injectable progestin contraception in South Africa: a prospective cohort study. AB - BACKGROUND: Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET EN), confer different risks of HIV-1 acquisition. METHODS: We included data from South African women who used injectable contraception while participating in theVOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012. Women were assessed monthly for contraceptive use and incident infection. We estimated the difference in incident HIV-1infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospective cohort. The VOICE trial is registered with ClinicalTrials.gov, NCT00705679. FINDINGS: 3141 South African women using injectable contraception were included in the present analysis: 1788 (56.9%)solely used DMPA, 1097 (34.9%) solely used NET-EN, and 256 (8.2%) used both injectable types at different times during follow-up. During 2733.7 person-years of follow-up, 207 incident HIV-1 infections occurred (incidence7.57 per 100 person-years, 95% CI 6.61-8.68). Risk of HIV-1 acquisition was higher among DMPA users (incidence 8.62 per 100 person-years, 95% CI 7.35 10.11) than among NET-EN users (5.67 per 100 person-years, 4.35-7.38;hazard ratio 1.53, 95% CI 1.12-2.08; p=0.007). This association persisted when adjusted for potential confoundingvariables (adjusted hazard ratio [aHR] 1.41, 95% CI 1.06 1.89; p=0.02). Among women seropositive for herpes simplex virus type 2 (HSV-2) at enrolment, the aHR was 2.02 (95% CI 1.26-3.24) compared with 1.09 (0.78 1.52)for HSV-2-seronegative women (pinteraction=0.07). INTERPRETATION: Although moderate associations in observational analyses should be interpreted with caution, thesefi ndings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence settings where NET EN is available. FUNDING: National Institutes of Health, Mary Meyer Scholars Fund, and the Ruth Freeman Memorial Fund. PMID- 26155601 TI - Extension of Effective Date for Temporary Pilot Program Setting the Time and Place for a Hearing Before an Administrative Law Judge. Final rule. AB - We are extending for one year our pilot program that authorizes the agency to set the time and place for a hearing before an administrative law judge (ALJ). Extending of the pilot program continues our commitment to improve the efficiency of our hearing process and to maintain a hearing process that results in accurate, high-quality decisions for claimants. The current pilot program will expire on August 10, 2015. In this final rule, we are extending the effective date to August 12, 2016. We are making no other substantive changes. PMID- 26155602 TI - Revocation of General Safety Test Regulations That Are Duplicative of Requirements in Biologics License Applications. Final rule. AB - The Food and Drug Administration (FDA) is amending the biologics regulations by removing the general safety test (GST) requirements for biological products. FDA is finalizing this action because the existing codified GST regulations are duplicative of requirements that are also specified in biologics license applications (BLAs), or are no longer necessary or appropriate to help ensure the safety, purity, and potency of licensed biological products. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation, in response to the Executive order. PMID- 26155603 TI - Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products. Final rule. AB - The Food and Drug Administration (FDA or the Agency) is amending its regulations to implement certain drug shortages provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA). The rule requires all applicants of covered approved drugs or biological products--including certain applicants of blood or blood components for transfusion and all manufacturers of covered drugs marketed without an approved application--to notify FDA electronically of a permanent discontinuance or an interruption in manufacturing of the product that is likely to lead to a meaningful disruption in supply (or a significant disruption in supply for blood or blood components) of the product in the United States. PMID- 26155604 TI - Effect of Social Factors on the Highest Global Incidence of Congenital Factor XIII Deficiency in Southeast of Iran. PMID- 26155605 TI - Laparoscopic Retroperitoneal Removal of Schwannoma. PMID- 26155606 TI - Authors' response. PMID- 26155607 TI - Problem solving with coronary CT angiography in cases of difficult coronary angiography. PMID- 26155608 TI - Delayed spinal cord ischaemia after hybrid thoraco-abdominal aneurysm (TAA) repair. PMID- 26155609 TI - Campylobacter: a change in public health approach. PMID- 26155610 TI - Two cases of primary adenocarcinoma of an ileal conduit: case reports and review of the literature. PMID- 26155611 TI - Adult small bowel malrotation--an audit of local practice. PMID- 26155612 TI - Trainee experience of open cholecystectomy in the laparoscopic era. PMID- 26155613 TI - [Rheumatic diseases and multimorbidity]. AB - In the past decade, investigators' undeniable and justified interest has not been fading in comorbidities in the presence of rheumatic diseases. The terms "comorbidity" and "multimorbidity" are frequently and not always consciously used as interinterchangeable, confusing the terminology and accordingly the elaboration of strategies for further researches. The concepts "(co-occurring disease" and "multimodality" are not mutually exclusive or contradictory, but these should be considered from another point of view than "comorbidity". The problem of multimorbid disease is the rule rather than the exception for clinicians treating primarily "typical" rheumatic patients. Recent researches could outline a few key areas for further study of the concept of multimorbidity in rheumatologic practice, which will be able to turn the international research community from rheumatic disease to the patient as a whole. PMID- 26155614 TI - [Time course of changes in the clinical manifestations of gout in men: data of a 7-year retrospective follow-up]. AB - AIM: To estimate the time course of changes in the clinical manifestations of gout and their risk factors during a long-term follow-up. SUBJECTS AND METHODS: A total of 160 male patients with gout were examined and followed up for a mean of 6.9 +/- 2.0 years. Their clinical assessment included determination of the type of arthritis over time, the frequency of arthritis attacks during one year prior to the examination, the presence and number of subcutaneous tophi, inflamed joints, comorbid or co-occurring diseases (CD), allopurinol adherence, dietary compliance, frequency of taking non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, and alcohol. The serum levels of uric acid (UA), glucose, total cholesterol, and glomerular filtration rate were estimated. RESULTS: The number of patients taking allopurinol increased from 19% to 64% (p < 0.0001), its average daily dose was 167.6 +/- 94.6 mg. The serum level of UA decreased; 16% of the patients achieved its target level. The number of patients with chronic arthritis was not significantly changed. Their serum level of UA was unchanged; the detection rate of subcutaneous tophi and CD rose. During one year, arthritis attacks were absent in 13% of the patients; 90% of them took allopurinol. In these patients, serum UA levels and body mass index significantly declined and the rate of CD was unchanged. None of 18 patients who had their diet and no allopurinol achieved the target level of UA. CONCLUSION: Among the gouty patients, 36% refrain from the use of allopurinol, only 23% out of them require that its dose be adjusted to achieve the target level of UA. Dietary compliance is insufficient to reach the target level of UA. Chronic arthritis is associated with the increased incidence of CD. PMID- 26155615 TI - [Left and right ventricular diastolic dysfunction in patients with early rheumatoid arthritis before prescribing disease-modifying antirheumatic therapy]. AB - AIM: To estimate the rate of diastolic dysfunction (DD) of the left and right ventricles (LV and RV) in patients with early rheumatoid arthritis (RA) before using disease-modifying antirheumatic drugs (DMARDs) therapy and to investigate its association with traditional risk factors (TRFs) for cardiovascular diseases (CVD) and inflammatory markers. SUBJECTS AND METHODS: The investigation enrolled 74 patients with a valid diagnosis of RA, including 56 (74%) women (median age, 54 years; disease duration, 7 months); the patients who were seropositive for rheumatoid factor (RF) (87%) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies (100%) who had not been on DMARDs or glucocorticosteroids. TRFs for CVD and carotid artery atherosclerosis were assessed from duplex scanning data and echocardiography was performed in all the patients with early RA before starting the therapy. The ratio of the maximum blood flow velocity during early diastolic filling (E) to that during atrial systole (A) was used as a criterion for LVDD and RVDD. There were 3 types of impaired ventricular filling: 1) E/A <1; 2) E/A = 1-2; 3) E/A > 2. RESULTS: LVDD and RVDD were detected in 35 (48%) and 17 (23%) patients, respectively. RVDD was recorded only in conjunction with LVDD. Among LVDD and RVDD, the former was prevalent. All the patients with early RA were divided into 3 groups: 1) patients with LVDD and RVDD; 2) those with LVDD; 3) those without ventricular DD. All the three groups were matched for the level of DAS28, anti-CCP antibodies, and RF. The incidence of arterial hypertension, dyslipidemia, and abdominal obesity was higher in the patients of Groups 1 and 2 than in those of Group 3. There was a progressive decrease in high-density lipoprotein (HDL) cholesterol concentrations and increases in triglyceride (TG) levels and atherogenic index from Group 3 to Group 1, with the concentrations of total cholesterol and low-density lipoprotein cholesterol being similar in the 3 groups. Coronary heart disease was recorded more frequently in Group 2 than in Group 3. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) proved to be also significantly higher in the patients with DD than in those without DD. Correlations were found between LV E/A and ESR, CRP, HDL cholesterol, TG, RV E/A and ESR, DAS28, TG. CONCLUSION: The patients with early-stage RA were found to have high incidence rates of LVDD and RVDD, which is related to the high prevalence of CVD, the high spread of TRF for CVD, and the high activity of an inflammatory process. PMID- 26155616 TI - [Clinical and hemodynamic characteristics and possibilities for therapy in patients with severe (functional class IV) pulmonary arterial hypertension associated with diffuse connective tissue diseases]. AB - AIM: To study the clinical and hemodynamic characteristics of a group of patients with Functional Class (FC) IV pulmonary arterial hypertension (PAH) developing in the presence of diffuse connective tissue diseases (DCTD) and to evaluate the efficacy of intravenous iloprost. SUBJECTS AND METHODS: The study enrolled 59 patients with PAN-DCTD, including 7 who had FC IV and 8 who developed this condition during a follow-up. The diagnosis of PAH was based on pulmonary artery catheterization findings. FC IV was diagnosed using the conventional New York Heart Association classification. All the patients received PAH-specific therapy (bosentan, sildenafil); the patients with FC IV had combined therapy; 4 patients were treated with intravenous iloprost calculated with reference to 0.5-2.5 ng/kg/min for 15 days. In addition to the patients with FC IV, 3 patients with unstable FC Ill were given iloprost. Besides targeted therapy, all the patients received standard treatment, including diuretics, and ionotropic therapy. RESULTS: Evaluation of hemodynamics in patients with different FCs revealed the most important differences in right atrial pressure, cardiac output, cardiac index, and pulmonary vascular resistance. A linear relationship was seen between the level of this indicator and FC, the closest correlation being for hemodynamic parameters characterizing right ventricular systolic function. There were no changes in mean pulmonary artery pressure; only the patients with FC IV were found to have its slight elevation (from 52 +/- 15 to 55 +/- 11 mm Hg). Pulmonary artery wedge pressure remained unchanged regardless of FC. Intravenous iloprost was noted to have an obvious positive effect on both clinical and hemodynamic parameters. Catheterization verified improvement in 6 out of the 7 patients; no hemodynamic changes were found in 1 patient during 15-day therapy. CONCLUSION: The patients with FC IV PAH-DCTD have clinical and hemodynamic features responsible for a fatal prognosis. The results of using intravenous iloprost in patients with decompensated PAH associated with scleroderma systematica convince to use its PAH-specific tablets in cases of verified clinical deterioration when taking its dosage form. PMID- 26155617 TI - [Microscopic polyangiitis associated with antineutrophil cytoplasmic antibodies: clinical features]. AB - AIM: To study the clinical features of early- and extended-stage microscopic polyangiitis (MPA) and its outcomes on the basis of a long-term follow-up in a rheumatologist's practice. SUBJECTS AND METHODS: The clinical features of early- and extended-stage MPA were studied in detail and the premorbid background and possible precipitating factors were analyzed in 70 patients with MPA and the proven hyperproduction of antineutrophil cytoplasmic antibodies (anti-proteinase 3 (anti-PR3) antibodies in 55% and anti-myeloperoxidase (anti-MPO) antibodies in 45%) who had been followed up for more than a year. RESULTS: There is evidence for the nosological unity of the two immunological types of MPA associated with anti-PR-3 or anti-MPO antibodies. MPA has been demonstrated to be an aggressive, polysyndromic disease prone to recurrences (52%), the typical manifestation of which is glomerulonephritis (94%) that is rapidly progressive in every four cases and accompanied by hemorrhagic alveolitis (69%) and involvement of other organs. ENT organs and lungs have been noted to be commonly involved in early-stage MPA, which was observed in 61% of the patients in the premorbid period, and to become the first manifestation of MPA (63%) concurrent with body temperature rises (64%), arthralgia or arthritis (41%). Respiratory tract involvement in MPA may be asymptomatic. Anti-PR-3-associated MPA may manifest itself more aggressively and in the first 2 years it is characterized by a poorer prognosis than of anti-MPO associated MPA (survival rates, 82 and 94%, respectively; p = 0.04). With time, the differences were levelled off; recurrences in the patients with anti-PR-3 and anti-MPO develop equally frequently and proceed showing the similar clinical picture; the survival curves converge by age 3. Anti-MPO-associated MPA is characterized by the highest rate of lung involvement in the clinical phase of the disease (61%) and by a propensity to develop hemorrhagic alveolitis, diffuse interstitial (22%) or circumscribed pulmonary fibrosis in the outcome. CONCLUSION. The findings emphasize how important to diagnose MPA early and to prescribe long-term active treatment using the entire current arsenal of medications as soon as possible until severe injury to organs and systems develops. To specify regularities in the development of MPA may be of value for the better diagnosis of the disease and the further elaboration of optimal treatment policy. PMID- 26155618 TI - [Efficacy and safety of intravenous methylprednisolone in the treatment of patients with active ankylosing spondylitis: results of a 12-week, prospective, open-label, pilot (METALL) study]. AB - AIM: To evaluate the efficacy and safety of intravenous methylprednisolone (MP) 500 mg in patients with active ankylosing spondylitis (AS) and the inefficiency, intolerability of or contraindications to treatment with 2 or more non-steroidal anti-inflammatory drugs (NSAIDs). SUBJECTS AND METHODS: The investigation enrolled 20 patients (age, 35.35 +/- 8.19 years) with a 10.2 +/- 9.2 year history of AS who met the modified New York criteria) and had its activity defined as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >= 4 scores and an inadequate response to and intolerance of >= 2 NSAIDs; there were 13 (65%) men. MP was given in a single intravenous dose of 500 mg. The main efficiency criterion (primary study endpoint) was considered to be the number of patients who had achieved an ASAS20 response at week 2. Additional rating criteria (secondary endpoints) (improved BASDAI/ASDAS; decreased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels; the number of patients achieving ASAS20/40/5/6 responses and ASAS partial remission, and improved ASDAS) were calculated 2, 4, and 12 weeks after MP administration. Safety was monitored estimating the frequency of adverse events (AEs) and controlling vital functions and laboratory indicators. RESULTS: Nine (45%) patients achieved an ASAS40 response at week 2. ASDAS was 3.48 at baseline and 2.21 at week 2 (p < 0.0001). ASDAS clinical improvement was established in 11 (55%) patients at week 2. There were decreases in BASDAI from 6.6 to 3.7 at week 2, to 3.5 at week 4, and to 3.2 at week 12 (p < 0.001). CRP levels declined from 6.1 to 3.15 mg/l at week 2 (p < 0.05), to 2.85 mg/l at week 4 (p < 0.001), and to 4.6 mg/l at week 12 (p < 0.05). ESR was 6.5 mm/h at baseline, 5.5 mm/h at week 2 (p < 0.05), 6.0 mm/h at week 4, and 7.0 mm/h at week 12 (p > 0.05). A total of 13 AEs were recorded and no serious AEs were noted. CONCLUSION: Pulse therapy with MP 500 mg is safe and effective in the short-term treatment of patients with active AS who have achieved no benefits of NSAIDs. PMID- 26155619 TI - [Cerebrovascular risks and prediction of complications in patients with backache during therapy with nonsteroidal anti-inflammatory drugs]. AB - AIM: To study the impact of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, meloxicam, etoricoxib, and nimesulide, on systolic and diastolic blood pressure (BP) changes in a short period (3 days), as well as the risk of acute transient ischemic attack, ischemic and hemorrhagic stroke, and acute cardiovascular events within 6 months after NSAID use. SUBJECTS AND METHODS: The follow-up included 66 patients (34 women and 32 men) who took NSAIDs for emergent low back pain. RESULTS: The findings may suggest that etoricoxib based therapy is highly effective and relatively safe for the management of acute nonspecific backache in patients with comorbidity. The important feature is the established tendency towards BP destabilization in patients with chronic cerebrovascular diseases treated with NSAIDs (diclofenac, meloxicam, to a lesser extent, nimesulide). After completion of drug intake for 14 days or longer, acute cerebral circulatory disorder and acute cerebrovascular event developed within 4.5 months in 3 and 2 patients, respectively. CONCLUSION: Thus, the spectrum of possible adverse cardiovascular effects of NSAIDs is rather broad. It is advisable to identify two major groups of NSAID-associated complications: 1) destabilized hypertension; 2) cardiovascular and cerebrovascular events. PMID- 26155621 TI - [Osteoarthritis in the adult population of the Republic of Kazakhstan]. AB - AIM: To analyze overall and new-onset osteoarthritis (OA) morbidity among the adult population in the Republic of Kazakhstan in 2011-2012. SUBJECTS AND METHODS: The data of annual statistical reports "On Population Health and Public Health System" (Form No. 12) in 2011-2012 were analyzed. The indicators in the Republic of Kazakhstan were taken from the statistical collected articles "Population Health in the Republic of Kazakhstan and Activities of Healthcare Facilities". RESULTS: A comparative analysis of the indicators revealed a rising trend in overall morbidity by 1%, including in the incidence of musculoskeletal diseases (MSD) by 3% (the increase rate per 100,000 population was 2%). An analysis of the incidence of MSD per 100,000 population in some regions of the Republic of Kazakhstan showed an upward trend in the Almaty Region: the incidence increased among the women and the 18 or more year olds by 23 and 16%, respectively. Among the adults (aged 18 years or older) and women, the number of patients with a newly diagnosed coxarthrosis (CA) increased by 43 and 18%, respectively; the number of those with gonarthrosis (GA) rose by 36 and 33%, respectively. The people older than 60 years of age and women showed 122 and 82% rises in the number of patients with a newly diagnosed CA; there were 78% increment rates in the patients with GA and 68% in the women. CONCLUSION: In the Republic of Kazakhstan, there was a high incidence of OA in both the people aged 18 years or older with newly diagnosed CA, GA and the people over 60 years of age, in women in particular. PMID- 26155620 TI - [Analysis of the state-of-the-art of consulting medical care to patients with glucocorticoid-induced osteoporosis or its risk according to the data of a questionnaire survey (GLUCOST study)]. AB - AIM: To analyze the state-of-the-art of consulting medical care to Russian patients with glucocorticoid-induced osteoporosis (GCOP) or its risk. SUBJECTS AND METHODS: This GLUCOST study was organized and conducted by the Russian Association of Osteoporosis. A total of 1129 patients with chronic inflammatory diseases, who had been taking oral glucocorticosteroids (OGCSs) a long time (3 months or more), were examined. The patients filled out an anonymous questionnaire on their own. Whether the measures taken to diagnose, prevent, and treat GCOP complied with the main points of Russian clinical guidelines was assessed. RESULTS: 61.8% of the patients knew that the long-term treatment of GCOP might cause osteoporosis. 48.1% of the respondents confirmed the results of bone densitometry; 78.1% of the patients reported that they had been prescribed calcium and vitamin D supplements by their physician, but their regular intake was confirmed by only 43.4%; 25.4% of the patients had sustained one low-energy fracture or more. Treatment for GCOP was prescribed for 50.8% of the patients at high risk for fractures, but was actually received by 40.2%. Therapeutic and diagnostic measures were implemented in men less frequently than in women. When the patient was aware of GCOP, the probability that he/she would take calcium and vitamin D supplements rose 2.7-fold (95% Cl; 2.1 to 3.5; p = 0.001) and that he/she would follow treatment recommendations did 3.5-fold (95% Cl; 2.3 to 5.3; p = 0.001). Bone densitometry increased the prescription rate for antiosteoporotic medication and patient compliance. CONCLUSION: According to the data of Russia's large-scale GLUCOST survey, every four patients with chronic inflammatory disease who are on long-term OGCS therapy have one low-energy fracture or more. Due to inadequate counseling, the patients are little aware of their health and do not get the care required to prevent the disease. Less than 50% of patients who have GCOP and a high risk for fractures undergo examination and necessary treatment aimed at preventing fractures. PMID- 26155622 TI - [Neurogenic copulative dysfunction in men: theoretical aspects, differential diagnosis, and rational therapy]. AB - Neurogenic copulative dysfunction (CD) is observed in different diseases and injuries of both the central and peripheral nervous system. CD concurrent with actual nervous system diseases has been established to be an important psychotraumatic factor that significantly reduces quality of life in these patients. AIM: To investigate the effect of aminophenylbutyric acid (Noophen) on male copulative function. SUBJECTS AND METHODS: Forty patients with chronic lumbosacral radiculopathy on an exacerbation and mild and moderate closed head injury were examined. RESULTS: The findings suggest that Noophen is effective in the combination therapy of neurogenic CD. CONCLUSION: The drug can normalize an autonomic control over nerve centers involved in the regulation of copulative function, and improve the psychoemotional status of patients. PMID- 26155623 TI - [Evaluation of endothelial function and estimation of the degree of apoptosis in patients with metabolic syndrome and non-alcoholic fatty liver disease]. AB - AIM: To evaluate endothelial function (EF) and to estimate the level of a serum apoptosis marker (caspase-8) in patients with metabolic syndrome (MS) and in those with non-alcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS: The investigation enrolled 76 patients: 43 with MS (out of them, 72.1% were found to have NAFLD) and 33 without MS and NAFLD. All the patients underwent evaluation of EF by photoplethysmography; the level of caspase-8 as one of the apoptosis markers was studied in all. RESULTS: Increased arterial stiffness was more common in a group of patients with MS. Systolic duration was higher in these patients (p < 0.05). In these patients, an occlusion test revealed the significantly more marked signs of endothelial dysfunction (ED), which correlated with some cardiovascular diseases (CVD), and hepatic steatosis (p < 0.05). The mean level of caspase-8 was significantly higher in the group of MS patients (p < 0.05). There was a positive correlation between caspase-8 levels and hepatic and pancreatic steatosis, obesity, aortic atherosclerosis, type 2 diabetes mellitus, and gastroesophageal reflux disease (p < 0.05). CONCLUSION: The study group of MS patients (among whom, there was a preponderance of those with NAFLD) had, firstly, higher arterial stiffness more frequently (as evidenced by photoplethysmography), secondly, longer systolic duration, which may be a risk factor for CVD; thirdly, more pronounced ED. Fourthly, according to the data of a study of caspase-8 levels, its indicator may serve as a prognostic marker for the development of CVD and NAFLD. It was, fifthly, shown that the administration of statins might reduce the degree of apoptosis. PMID- 26155624 TI - [Hemophagocytic syndrome in a patient with adult-onset Still's disease: diagnostic problems]. AB - Hemophagocytic syndrome (HPS) is a rare life-threatening condition caused by massive cytokine release from activated macrophages and lymphocytes. The paper depicts the development of HPS in different infections, malignancies, and autoimmune diseases. It describes a clinical case of hemophagocytic syndrome in a 63-year-old female patient with adult-onset Still's disease and high fever accompanied by neutrophil leukocytosis and a drastic left leukocyte count shift, high procalcitonin levels, hepatosplenomegaly, edematous syndrome, and progressive multiple organ dysfunction with the development of disseminated intravascular coagulation and adult respiratory distress syndrome. The diagnosis of HPS was established according to the diagnostic criteria and verified by autopsy: phagocytes in liver and lung tissues. PMID- 26155625 TI - [Primary hepatic lymphoma in a female patient with Sjogren's disease: A case report and literature review]. AB - The paper describes a case of primary hepatic diffuse large B-cell lymphoma in a 52-year-old woman with a 27-year history of Sjogren's disease. It gives the data available in the literature on the etiology, diagnosis, and morphological characteristics of primary hepatic lymphoma and touches upon the issues of differential diagnosis. PMID- 26155626 TI - [Behcet's disease and malignization: literature review and authors' data]. AB - The paper describes cancers (enteric adenocarcinoma in one case and acute leukemia in the other) in 2 patients with Behcet's disease (BD) followed up at the V.A. Nasonova Research Institute of Rheumatology. It gives the data available in the literature on BD concurrent with malignant tumors. This concurrence is noted to substantially worsen the prognosis of the disease as a whole. PMID- 26155627 TI - [Systemic vasculitides: some debatable aspects of the problem]. AB - A new nomenclature of systemic vasculitides (SV) and current approaches to their treatment have necessitated the discussion of some debatable questions on this condition. The paper gives the data of examining 325 patients with different forms of SV, followed up in the Interregional Consulting Center for SV patients, and the results of testing the American College of Rheumatology classification criteria for SV and the authors' criteria, by taking into account the International Chapel Hill Consensus Conference, USA (1994 and 2011) guidelines for CV nomenclature. It discusses the etiological factors and pathogenetic components of SV, morphological aspects, and relationships between the local and systemic forms of SV. The findings were compared with the data available in the literature. It is concluded that differentially diagnostic criteria for CV should be elaborated to specify the stage of the disease, the activity and use of adapted therapy regimens. PMID- 26155628 TI - [Algorithm for the management of patients with ventricular arrhythmias]. AB - The paper proposes an original algorithm for the management of patients with ventricular arrhythmia from its first registration to choice of treatment policy. Using modern diagnostic methods, much attention is paid to the identification of myocardial structural and ischemic changes and also to the involvement of the autonomic and central nervous systems in ventricular arrhythmogenesis. The diagnostic problems are solved step-by-step. The role of psychological diagnosis is accentuated. Longitudinal electrocardiogram monitoring with telemetric data transmission can promptly initiate treatment of patients in an outpatient setting and, in a number of cases, without discontinuing work. The key point of the algorithm proposed is to prevent sudden cardiac death. PMID- 26155629 TI - [Biological agents and fracture risk]. AB - In patients with chronic inflammatory diseases, including rheumatic ones, the risk of fractures exceeds that in the population. Chronic inflammation is one of the most discussed and most important pathogenic factors of reduced bone mineral density (BMD), its worse quality and increased fracture risk. The chronic inflammatory process contributes to the imbalance of bone remodeling toward bone resorption. The use of biological agents in patients with rheumatic and other autoimmune diseases effectively suppresses systemic inflammation and increases BMD. However, the effect of the biological agents in lessening the risk of fractures remains unproven. PMID- 26155630 TI - [Alginates in therapy for gastroesophageal reflux disease]. AB - This article presents evidence of the prevalence of gastroesophageal reflux disease (GERD) and highlights its main treatment options. Among its medications, particular emphasis is laid on alginates and their main mechanisms of action are described. There is information on the efficacy of alginates, including the alginate-antacid Gaviscon Double Action, in treating GERD. Recommendations for how to administer these drugs are given. PMID- 26155631 TI - [Role of animal gastric Helicobacter species in human gastric pathology]. AB - Animal Helicobacter species other than Helicobacter pylori are also able to cause human gastritis, gastric ulcers, and MALT lymphomas. Animal Helicobacter species are presented with typical spiral fastidious microorganisms colonizing the gastric mucosa of different animals. Bacteria initially received their provisional name Helicobacter heilmannii, and out of them at least five species colonizing the gastric mucosa of pigs, cats, and dogs were isolated later on. A high proportion of these diseases are shown to be zoonotic. Transmission of pathogens occurs by contact. The factors of bacterial pathogenicity remain little studied. PMID- 26155632 TI - [Place of probiotics in the prevention and treatment of antibiotic-associated diarrhea]. AB - The paper gives data on the prevalence and etiopathogenesis of antibiotic associated diarrhea and describes the major pathogens of this disease and methods for their diagnosis. It considers treatment policy in detail, with an emphasis on the use of probiotics for both the prevention and therapy of the disease described. Russian investigations on the alleged topic of a Linex probiotic complex, as well as the authors' original trial of this medication are presented. PMID- 26155633 TI - [FEATURES OF THE ORGANIZATION OF SANITARY-EPIDEMIOLOGICAL SURVEILLANCE DURING THE PERIOD OF PREPARATION AND HOSTING OF THE XXII OLYMPIC WINTER GAMES AND XI PARALYMPIC WINTER GAMES IN THE RESORT CITY OF SOCHI IN 2014]. AB - In the paper there are presented the basic principles of the organization of activities for the assurance ofthe sanitary- epidemiological welfare in the period ofpreparation and hosting of the XXII Olympic Winter Games and XI Paralympic Winter Games of 2014 in the Resort City of Sochi. There are considered features of the organization ofepidemiological surveillance in the pre-Olympic period, the period of the games and the state of the morbidity rate in the region after the Olympics. There are presented data on certain directions of the work of organs and institutions of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare on the disease control of the event. PMID- 26155634 TI - [THE USE OF RISK ASSESSMENT METHODOLOGY IN THE MANAGEMENT OF SOCIAL-HYGIENIC MONITORING FOR AMBIENT AIR AND THE RELATIONSHIP OF POPULATION'S HEALTH STATE WITH THE AIR POLLUTION IN NIZHNEVARTOVSK]. AB - In the course of the work there was performed the assessment of the risk for the atmospheric air pollution for the health of the population of the city of Nizhnevartovsk Khanty-Mansi Autonomous Area with the purpose of identification of a priority pollutants and detection of levels of their exposure to the health. There is considered the morbidity of the population, groups of the risk most exposed to the impact of pollutants in atmospheric air have been revealed. There was performed the detection of main sources of pollution and there was elaborated risk mitigation measures. PMID- 26155635 TI - [ORGANIZATION OF THE QUALITY CONTROL OF PLACEMENT AND ACCOMMODATION OF PARTICIPANTS ATTENDANTS AND GUESTS OF THE XXII OLYMPIC WINTER GAMES AND XI PARALYMPIC WINTER GAMES OF 2014 IN THE RESORT CITY OF SOCHI]. AB - There is presented the analysis of activities of the Federal Service for Supervision of Consumer Rights protection and Human Welfare to ensure adequate conditions of accommodation of the participants, attendants and guests of the XXII Olympic Winter Games and XI Paralympic Winter Games of 2014 in the Resort city of Sochi according to regulated requirements. There were detected ways of the strengthening the supervision for the quality of the accommodation during mass sports activities for the assurance of the rights for consumers. PMID- 26155636 TI - [ASSESSMENT OF THE QUALITY OF DRINKING WATER AND RISK FOR THE POPULATION'S HEALTH IN RURAL TERRITORIES IN THE IRKUTSK REGION]. AB - The hygienic analysis of centralized and decentralized water supply in rural population in Irkutsk region was performed. About 403 thousand of the upstaters use water wells, voids and springs. In drinking water there were detected significant concentrations of iron, nitrates, manganese. On the base of the application of risk assessment methodology there was calculated noncarcinogenic risk for adults (HI = 1.2-1.3) and children (HI = 1.1-2.9). Carcinogenic risk for water from groundwater sources supply is 1.56 . 10(-5)-2.1 . 10(-4) for 22.2 thousand of upstaters. There were determined priority carcinogenic ingredients: arsenic (contribution is 56.3-100%) and hexad chromium (contribution is 29.9 35.8%). PMID- 26155637 TI - [EXPERIENCE OF THE MULTIPLE ENVIRONMENTAL ASSESSMENT OF RISKS FOR POPULATION'S HEALTH WITH THE AIM TO PROVIDE THE SAFETY OF THE POPULATION OF THE CITY OF CHELIABINSK]. AB - For the purposes of the determination of reasons for the high cancer rates in the population ofthe city of Chelyabinsk there was performed the multiple environmental assessment of the carcinogenic risk from chemicals dissolved in drinking water, food, soil, air (from stationary sources). Based on this assessment there were determined the directions for sanitary and environmental measures. PMID- 26155638 TI - [SMOKING PREVALENCE AND RISK FOR THE SMOKING- RELATED LOSS OF HEALTH OF THE POPULATION OF THE KRASNOIARSK KRAI]. AB - There are presented data on the consumption of tobacco in the Krasnoyarsk Territory in the context of age-sex and social groups. Representatives of the workers specialties, students were shown to smoke more frequently, men smoke 2 times more often than women. For the population of the Krasnoyarsk Territory there were evaluated carcinogenic and non-carcinogenic risks for the loss of health, related with the factor of tobacco smoking. The significant portion of residents was established to accept tobacco smoking. The lack of a purposeful policy on the formation of the image of a non-smoker does as not only increase the interest in this bad habit from the part of young people as well determined the early age of the beginning of smoking, but also stimulates the continuation of smoking in an older age. The measures aimed at the reduction or cessation of smoking: education the population and informing about the dangers of smoking, promotion of healthy lifestyles; offensive disciplinary, civil, administrative responsibility; measures aimed on the increase in the cost, the provision of (free) medical care aimed at the treatment of tobacco dependence. PMID- 26155639 TI - [ASSESSMENT OF THE RISK OF ENVIRONMENTAL ATMOSPHERIC POLLUTANTS FOR THE HEALTH OF THE POPULATION OF THE CITY OF NORIL'SK]. AB - There are presented data on the non-carcinogenic and carcinogenic risks, the actual morbidity rate ofthe population of the city of Norilsk of the Krasnoyarsk Krai in relation with atmospheric air pollution by chemical substances. Contamination of the ambient air by harmful substances is shown to cause the formation of the unacceptable risks to the population's health. There are established relationships described by the equation of pair correlation between the air pollution indices and morbidity rates of the population. There are determined the proportions of the contributions of enterprises and atmospheric pollutants in the formation of children morbidity. There are detected priority ambient air contaminants for a substantiation of programs of preventive measures. PMID- 26155640 TI - [APPROACHES TO ENHANCING THE ORGANISM'S RESISTANCE TO THE ADVERSE EFFECTS OF NANOMATERIALS AS EXAMPLIFIED BY NANOSILVER AND NANOCOPPER OXIDE]. AB - Subchronic intoxications in rats induced by repeated intraperitoneal injections of stable water suspensions of silver or copper oxide nanoparticles in low dosage were manifested by adverse shifts in some functional and biochemical indices, by development of histo-structural changes in different tissues and by poly-organ fragmentation of DNA. All these manifestations of toxicity were substantially attenuated against the background of parallel oral administration of bioprotective complexes comprising vitamins, trace elements, pectin, some amino acids and a fish oil preparation rich in omega-3 fee fatty acids, this composition has been adjusted to mechanisms of action of this or that nanomaterial. PMID- 26155641 TI - [ANTIBIOTIC RESISTANCE OF SALMONELLA SPP. ISOLATED IN THE TERRITORY OF THE KRASNOIARSK REGION]. AB - There were studied Salmonella spp. isolated from various objects (sick patients, bacteria carriers, food, sewages) in the Krasnoyarsk region. Susceptibility to antimicrobial drugs was estimated with disc diffusion method. Bacterial cultures form sick patients were highly susceptible to aminoglycosides (amikacin and gentamicin)--susceptible strains accounted for 98-99%, carbapenems (imipenem)- 100%, cephalosporins (cephtriaxone)--97.8%, fluoroquinolones (ophloxacin)--95.8%, quinolones (ciprofloxacin)-- 88.9%, chloramphenicol--86.8%. Salmonella showed lesser susceptibility to sulphamethoxazole/trimethoprim 81.4%. Ampicillin--73.6% inhibitor protected antibiotic amoxicillin/clavulanic acid--86.4%. Salmonella spp. are the most resistant to tetracycline, the proportion of susceptible strains was less than a third--22.1%. The comparison of resistance of serovar S. enterica Enteritidis. with other serologic strains 'of S. enterica (S. Typhimurium, S. Infantis, S. Tshiongtve, S. Agama et al.) revealed greater resistance of anot Eneteritidis)) isolates to ampicillin, amoxicillin/ clavulanic acid,. ciprofloxacin and greater differences in resistance were to ofloksacin and, co-trimoxasol. The most high resistance ofthe all serovars S. enterica is to tetracycline (S. Enteritidis--26.2%, "non Enteritidis"--9.1%). Thus salmonella circulating in the Krasnoyarsk region are characterized by susceptibility to the most of antimicrobial drugs. The high resistance of islitates is revealed to tetracycline, ampicillin and sulfonamides. PMID- 26155642 TI - [THE RISK OF THE DEVELOPMENT OF OCCUPATIONAL CHRONIC FLUORIDE POISONING]. AB - On the basis of individual occupational fluoride loads (IOFN) it was established that under current levels of air pollution of the working area by fluorine compounds, occupational fluorosis can occur in mostly sensitive workers with 66 or more years of accumulated period of work, while the most vulnerable are workers with of 9.4 or more years of accumulated period of work. The results obtained in comparison of clinical data with individual fluoride load, testify that in the high-risk group for the development of occupational fluoride intoxication include workers with an average accumulated period of work of 10.5 years or more and Individual Occupational Fluoride Load (IOFL) as 67,7 or more grams. In the high-risk group there are included workers with an average accumulated period ofwork of 13.7 years and IOFL as 89.8 grams or more. With the use of ultrasound densitometry there was revealed a clear cut dynamics of the increase of the speed of ultrasonic wave with the rise in the accumulated period of work at the plant, which indicates to a gradual increase in bone tissue density. PMID- 26155643 TI - [MEDICAL AND PREVENTIVE MEASURES FOR REDUCING CHEMICAL OCCUPATIONAL RISKS IN THE PRODUCTION OF TITANIUM ALLOYS]. AB - An innovative approach in the prevention and rehabilitation of workers employed in the production of titanium alloys envisages the implementation of targeted multi-stage rehabilitation measures in groups with high occupational risk. PMID- 26155644 TI - [COMPARATIVE ANALYSIS OF THE IMMUNE PROFILE OF METALLURGICAL WORKERS EXPOSED TO DIFFERENT CHEMICAL FACTORS OF PRODUCTION ENVIRONMENT]. AB - There was performed a comparative analysis of the parameters of humoral immunity factors and topical immunity of 3000 workers of metallurgical enterprises exposed to effects of industrial mixts of different composition. Under exposure to aerosols with weak fibrogenic action there is observed simultaneous decrease of the number T-cytotoxic lymphocytes, and the increase of the number of T-helper cells, as under the influence of aerosols of complex composition (contains compounds with fibrogenc action--Silicon and irritants--nitrogen dioxide, sulfur there are formed signs of hyperergic immune response with the activation of humoral compartment, T-helper cells, and the inhibition of cytotoxic lymphocytes. Aerosols with fibrogenic action have the most pronounced suppressive effect on topical immunity PMID- 26155645 TI - [DETERIORATIONS OF HEALTH CONDITION IN FURNACE AND SMELTER EMPLOYEES OF THE TITANIUM AND MAGNESIUM INDUSTRY]. AB - There is presented the assessment of the impact of occupational risk factors on the health status of workers, carried out on the results of hygienic analysis of working conditions and the clinical and laboratory examination of workers. PMID- 26155646 TI - [FEATURES OF THE IMMUNE GENETIC PARAMETERS IN WORKERS IN NON-FERROUS METAL INDUSTRY]. AB - There was performed a comparative analysis of immunogenetic indices in non ferrous metallurgy employees under the exposure to different combinations of harmful occupational factors. The combined effect of chlorine and vanadium fumes, noise, overall vibration appeared to be associated with the gene polymorphism of cytokine regulation--VEGF and TNF (p < 0.05). In workers the combination offactors such as dust containing silicon dioxide, noise, elevated environmental thermal load was associated with cytochrome p450 gene polymorphism, allele variation ofwhich is formed owing to the homozygous genotype. At the same time there was observed an excess production of specific antibodies to vanadium and silicon, significantly differed from that of the indices in the reference group. There are proposed genetic (CYP1A1, VEGF TNFalfa) and immunological (IgG to vanadium and silicon) indices as markers of susceptibility and effect in health risk assessment of different combinations of harmful occupational factors, which will allow to increase the availability of laboratory control during surveillance activities at the objects. PMID- 26155647 TI - [ASSESSMENT ASSESSMENT OF THE CHEMICAL RISK AND ITS PREVENTION IN MANUFACTURE OF REFRACTORIES USING ORGANIC BINDER]. AB - Assessment of the occupational chemical risk of new industries and the development of measures for its mitigation is a priority task to ensure chemical safety in Russia. There was performed the assessment of the chemical risk in the manufacture of new types of refractories--periclase-carbon refractories, using organic binder) on the base of data of hygiene studies, indices of morbidity rates in workers and also of the investigation of the impact of such refractory dust on laboratory animals (intratracheal introduction). The main factors for chemical risk to the workers' health are magnesium oxide, volatile products of phenol-formaldehyde resins, silicon-containing dust, carbon monoxide, sulfur dioxide, nitrogen oxides, and in the use of a binder "Carbores"--benzo (a) pyrene and pitch cokes of the carbon dust. In employees of such industry there is recorded the elevated morbidity rate of diseases of upper respiratory rates. Dust of this type has on the body of animals general toxic and mild fibrogenic effect. According to the results of the assessment of the chemical risk measures have been developed for its mitigation in the workplace. PMID- 26155648 TI - [IMPACT OF THE CHEMICAL OCCUPATIONAL FACTORS ON THE DEVELOPMENT OF ALLERGIC DISEASES IN HEALTHCARE PRACTITIONERS]. AB - There was performed the assessment of the degree of the impact of the chemical occupational factors on the development of allergic diseases in healthcare practitioners of the Sverdlovsk Region. According to results of the certification of 145 workplaces in medical institutions of the Sverdlovsk Region's it was revealed that the health care professionals mostly contact with the chemical substances which were the strong allergens with potent nfavorable impact on the health. In the formation of allergic diseases in healthcare practitioners the leading role is belonged to antibiotics, vitamins and other medicines, as well as formaldehyde; there is less detected sensitization to cotton dust and synthetic detergents. PMID- 26155649 TI - [CHEMICAL AIR POLLUTION OF THE OCCUPATIONAL ENVIRONMENT AS A FACTOR FOR PROFESSIONAL RISK FOR WORKERS OF MAIN OCCUPATIONS IN THE COPPER AND NICKEL METALLURGY]. AB - There are presented the results of hygienic researches of the harmful substances content in the air of the working area ofthe copper and nickel metallurgy. Sulfur containing gases (primarily sulfur dioxide), to the effects of which there are exposed workers of drying, smelting, converter conversion, are shown to play a leading role among professional factors. PMID- 26155650 TI - [DISSOCIATION OF DISORDERS OF CARBOHYDRATE AND LIPID METABOLISM IN ALUMINUM INDUSTRY WORKERS ACCORDING TO MEDICAL EXAMINATION DATA]. AB - There were analyzed results of a periodical medical examination of 396 aluminum plant workers. There was established the significant dissociation of carbohydrate and lipid metabolism indices in people contacting with elevated concentrations qf inorganic fluorine compounds as compared to control group of patients which were not exposed to the toxic chemicals. This can testify to the risk of early onset of diabetes mellitus type 2 for aluminum industry workers and to the necessity of the implementation of timely measures for this worker category. PMID- 26155651 TI - [OCCUPATIONAL CANCER RISK. ASPECTS. EXPERTISES]. AB - This paper describes the problems associated with the solution of the expert questions with regard to the occupation-related malignant tumors. There are proposed approaches for the constructing a system of the reasoned expert decisions based on the results provided by the International Agency for Research of Cancer and the retrospective assessment of individual cancer risk. PMID- 26155652 TI - [OCCUPATIONAL HEALTH RISK ASSESSMENT AND MANAGEMENT IN WORKERS IN IMPROVEMENT OF NATIONAL POLICY IN OCCUPATIONAL HYGIENE AND SAFETY]. AB - In accordance with the international documents in the field of occupational safety and hygiene, the assessment and minimization of occupational risks is a key instrument for the health maintenance of workers. One of the main ways to achieve it is the minimization of occupational risks. Correspondingly, the instrument for the implementation of this method is the methodology of analysis of occupational risks. In Russian Federation there were the preconditions for the formation of the system for the assessment and management of occupational risks. As the target of the national (state) policy in the field of occupational safety in accordance with ILO Conventions it can be offered the prevention of accidents and injuries to health arising from work or related with it, minimizing the causes of hazards inherent in the working environment, as far as it is reasonably and practically feasible. Global trend ofusing the methodology of the assessment and management of occupational risks to life and health of citizens requires the improvement of national policies in the field of occupational hygiene and safety. Achieving an acceptable level of occupational risk in the formation of national policy in the field of occupational hygiene and safety can be considered as one of the main tasks. PMID- 26155653 TI - [TECHNOLOGIES FOR THE APPLICATION OF NATURAL HEALING FACTORS (THERAPEUTIC MUDS, MINERAL WATER) IN CHILDREN WITH THE PATHOLOGY OF HEPATOBILIARY SYSTEM RESIDING IN UNFAVORAUBLE ECOLOGICAL CONDITIONS]. AB - Health of children residing in the regions with polluted environment is significantly worse than the health of children not exposed to the emissions of industrial enterprises and motor vehicles. The gastrointestinal tract diseases occupy first places. There is elaborated the comprehensive treatment of the children with hepatobiliary diseases residing in unfavorable ecological conditions. There treatment includes factors possessing sanogenetic (mineral water therapeutic muds) and informative effects (EHF therapy). PMID- 26155654 TI - [THE CONTENT OF TRACE ELEMENTS IN THE HAIR OF YOUNGER SCHOOLCHILDREN IN VARIOUS CONDITIONS OF ANTHROPOGENIC LOAD]. AB - There was performed a comparative analysis of the contents of 12 chemical elements (Al, As, Ca, Cd, Co, Cu, Fe, K, Mg, Na, Pb, Zn) in 10-11 years old schoolchildren, residing in the city and Sayanogorsk and Askiz rural area of the Republic of Khakassia. There are established differences in the trace elemental status of schoolchildren residing in areas with different anthropogenic load. PMID- 26155655 TI - [METHODOLOGICAL APPROACHES TO THE ASSURANCE OF SANITARY-EPIDEMIOLOGICAL WELFARE ON THE BASE OF THE METHODOLOGY OF POPULATION'S HEALTH RISK MANAGEMENT]. AB - In the article there is considered the practice of the application of the current legislative regulatory and procedural base for the occupational health and labor medicine (hygiene) issues. There are discussed issues of the assessment of occupational risks in enterprises of the Sverdlovsk region. There are proposed approaches to the creating the occupational risk management and assessment systems. PMID- 26155656 TI - [COMPARATIVE ASSESSMENT OF THE MULTIMEDIA CANCER HEALTH RISKS CAUSED BY CONTAMINATION OF THE KRASNOIARSK KRAI REGIONS' ENVIRONMENT]. AB - Krasnoyarsk Krai is a region with developed mining and processing industries, notoriously known industries, as sources of carcinogenic emission. For 55 administrative units of the Krai 303 large enterprises' industrial emissions were preliminary prioritized and their location was designated. Only 52% out of the carcinogens emitted into the ambient air by industries were controlled, in other environments the figures ranged from 20% (soil, food) to 48% (drinking water), 10 carcinogens were not controlled in the environment at all. Based on the results of ranking carcinogenic emission and analysis of the carcinogens monitoring in the environment in 2007-2011 31 substances were selected. A comparative analysis of multiple environmental carcinogenic risks showed that 78% of the areas, based on the receipt ofcarcinogensfrom two media, and 80% ofthe areas taking into account the receipt ofcarcinogens from three media attributed to the alarming level of risk for population, that requires continuous monitoring and routine health interventions for its mitigation. The maximal multiple environmental risk values that took into account inputs from all sources were close to the upper boundary alarming level of risk, in Divnogorsk (7,80E-04), Norilsk (7,97 E-04), Krasnoyarsk (8,84E-04) and Achinsk (9,4 E-04). The greatest inputs to total individual cancer risk from polluted ambient air were made by benzene, chromium VI, formaldehyde and nickel, from drinking water--by arsenic, aldrin and heptachlor from soil--by arsenic and lead. The ambient air input into total multiple environmental carcinogenic risk ranged from 31.5 to 99.5%, drinking water input--from 0.5 to 68.5%, soil--up to 0.1%. Areas with maximum levels of total carcinogenic risk are characterized by the highest levels of average long term indices of cancer development. The study discussed in this article has screening nature. Further in-depth researches for carcinogenic and toxic multimedia risks are required. PMID- 26155657 TI - [METHODS AND TECHNOLOGIES OF HEALTH RISK ANALYSIS IN THE SYSTEM OF THE STATE MANAGEMENT UNDER ASSURANCE OF THE SANITATION AND EPIDEMIOLOGICAL WELFARE OF POPULATION]. AB - The methodology of the analysis of health risk at the present stage of development of Russian society is in-demand at all levels of government management. In conjunction with the methods of mathematical modeling, spatial temporal analysis and economic tools the risk assessment in the analysis of the situation makes it possible to determine the level of safety of the population, workers and consumers, to select prior resources, and threat factors as a point for exertion efforts. At the planning stage risk assessment is a basis for the establishment of most effective measures for the minimization of hazard and dangers. At the realization stage the methodology allows to estimate the efficiency of measures; at the control and supervision phase it permits to select out priorities for the concentration of efforts on the objects of maximal health risk for population. Risk assessments, including the elements of evolutionary modeling, are incorporated in the system of state hygienic regulation, the formation of evidence base of harm to health, the organization of control and supervisory activities. This allows you to harmonize the domestic legal framework with ternational legal requirements and ultimately enhances the credibility of the Russian data on the safety of the environment products and services. There is seemed to be actual the further assignment of enforcement of methodology of health risk analysis in the field of assurance of sanitary and epidemiological well-being and health of employers; he development of informational and analytical base in the part of the establishment of models of dependencies "exposure-response" for different types and levels of exposure and risk contingents; the accuracy enhancement of estimations of exposure; improvement of the economic aspects of health risk analysis and forecasting of measures aimed at mitigation of the losses associated with the negative impact of manifold factors on the health of citizens. PMID- 26155658 TI - [HYGIENIC DIAGNOSIS--A KEY ELEMENT IN THE HEALTH-PREVENTION TECHNOLOGIES FOR THE POPULATION RESIDING IN CONDITIONS OF HIGHER CHEMICAL LOAD]. AB - This article is devoted to the review of methods and technologies of hygienic diagnostics implemented in the frameworks of the regional system of socio hygienic monitoring for the Sverdlovsk Region for the purposes of the management ofthe quality ofenvironment and the state ofthe population's health. Under conditions of impossibility to take immediate performance of radical technological and technical measures mitigating adverse effects of industries and road transport on the living environment and due to limitation of financial expenses, the proposed algorithm of actions helps to establish priority factors, environmental objects, and routes ofexposure, evaluate predicted values of a multiple environmental assessment of health risk, specify dose-response relations in environmental epidemiological studies, substantiate the choice of the most susceptible groups of population, for which the implementation of targeted rehabilitation gives the significant medical and economic efficiency. PMID- 26155659 TI - [METHODICAL APPROACHES, EXPERIENCE AND PERSPECTIVES OF THE IMPLEMENTATION OF THE RISK MODEL OF SURVEILLANCE ACTIVITIES IN THE SPHERE OF THE ASSURANCE OF SANITARY AND EPIDEMIOLOGICAL WELFARE OF POPULATION, POPULATION'S HEALTH RISK MANAGEMENT AND THE CONSUMER RIGHTS PROTECTION]. AB - Control and supervision measures--one of the main technologies of Federal Service for Supervision of Consumer Rights protection and Human Welfare in the overall system of risk management for public health and damage to property consumers, aimed at the solution of the prior tasks in the field of assurance of the sanitary and epidemiological welfare of the population and consumer rights protection. The effectiveness of this technology depends on the correct choice of priority objects of supervision, which form the main problems in the sanitary and epidemiological situation and in the consumer market. The application of is approach has led to more effective oversight activity and the improvement of a number of indices characterizing the achievement of the objectives in the common system of risk management for public health and property of consumers. PMID- 26155660 TI - [MEDICAL AND PREVENTIVE TECHNOLOGIES OF THE MANAGEMENT OF THE RISK OF HEALTH DISORDERS ASSOCIATED WITH EXPOSURE TO ADVERSE ENVIRONMENTAL FACTORS]. AB - It the article there are reported methodological approaches to the development of medical and preventive technologies for rendering specialized medical, diagnostic and preventive care to the population residing in polluted areas. There is proposed the classification of medical and preventive technologies of specialized care to the population with risk- associated pathologies based on principles of assessing the character and level of risk, etiopathogenetic regularities of the development of risk-associated pathological process and the extent of its clinical and laboratory manifestation. There were distinguished four groups of medical and preventive technologies having specific goals and tasks, there was determined the group targeting of the medical and preventive actions, the area of there application and forms of their implementation. There were presented the main directions of medical and preventive actions taken within the technologies applied to various groups. PMID- 26155661 TI - [THE OPTIMIZATION OF THE ACTIVITY OF ORGANS OF FEDERAL SERVICE FOR SUPERVISION OF CONSUMER RIGHTS PROTECTION AND HUMAN WELFARE IN THE SVERDLOVSK REGION]. AB - In the Sverdlovsk region there have developed and implemented methodological approaches to the optimization oj the activity of the Directorate and the Centre directed to the improvement of the sanitary and epidemiological surveillance and in the sphere of the protection of the rights of consumers in the framework of the development of an comprehensive regional system of risk management for the population's health in the Sverdlovsk region. PMID- 26155662 TI - [ANALYSIS OF THE METHODIC APPROACHES TO THE OCCUPATIONAL RISK ASSESSMENT AT THE ENTERPRISES OF THE SVERDLOVSK REGION]. AB - This study is devoted to the practice of the application of the current legislative regulatory and procedural base for the occupational health and safety issues. The issues of the occupational risks assessment at the enterprises of the Sverdlovsk region are discussed Approaches to the creation of the occupational risk management and assessment systems are proposed. PMID- 26155663 TI - [MANAGEMENT OF THE MULTIPLE ENVIRONMENTAL RISK FOR THE HEALTH OF THE POPULATION OF INDUSTRIALIZED CITIES OF THE SVERDLOVSK REGION]. AB - In the Sverdlovsk region for the assessment and management of environment and health of the population over more than 10 years there is used a methodology for the assessment of the multiple environmental risk, allowing to identify priority routes of toxicants entering the body, to evaluate the possible dose-response relationships and elaborate targeted measures for their correction. In the article there is shown how are effective management decisions, elaborated on the base of the results of the assessment of multiple environmental risk to public health in cities of Pervouralsk and Revda of the Sverdlovsk region and directed to the mitigation of the exposure to chemical factors of the environment. PMID- 26155664 TI - [Effects of Aging Brain and Activation Methods of Its Compensatory Resources]. AB - The review contains recently finding mechanisms of aging brain and of age associated imbalances of architecture and functions of brain neural systems. The compensatory resources of a brain and the methods of its cognitive training influencing the integrity and development of intellectual functions are described. It is shown meaning life style in dynamics of brain aging. PMID- 26155665 TI - [Optogenetics in Investigations of Brain Mechanisms of Behavior]. AB - Optogenetics--new method which enables the control of selected cell type activity using light. This method significantly enhances the capabilities of modern neurobiology. In the review, the general concept of optogenetics and recent results and prospects of application of this approach in psycho-behavioral studies are discussed. PMID- 26155666 TI - [The Dual Nature of the Electrical Signals of the Brain (Electrical and Electrochemical) Which Were Recorded With the Help Polarizable Electrodes From Inert Metals]. AB - In the modern neurophysiology opinion was confirmed that the electrical signals of the brain in the frequency band from DC to electroencephalogram recorded with metallic conductors of inert metal implanted in the brain are formed solely by changes in the electric field of the brain. This paper presents a review of the literature and our own data, according to which the formation of these signals involves two factors. One factor is a change in the charge of the electric double layer electrode having a capacitor property and change the value of its charge with changes in the electric field volume conductor--the brain. Another factor is an electrochemical signal is defined by local changes in the redox potential (E) neuronal-glial populations surrounding the electrode. The paper provides an overviews the electrical and electrochemical properties of the electrodes of the inert metals used in electrophysiology. It is shown that each of these factors has the characteristic parameters over time and amplitude. The data of own studies of local changes in E cortex accompanying brain's response to the implantation of electrodes in the brain's cortex, the natural behavior of animals in the wake-sleep, integrative brain function and effect of pharmacological agents. These results give evidence of the highly informative study of local changes in brain E in order to study energy metabolism in the brain of waking animals, and lay the foundation for the study of local changes in brain energy metabolism in free animal behavior. PMID- 26155667 TI - [GABA(A)-Coupled Cl-/HCO3(-)-ATPase: Candidate for an Novel Primary Active Transporter in Neuronal Membranes]. AB - Cl(-)-transport systems in cell membranes from various origins (including neurons) play an important role in different processes of their vital functions. Various transport mechanisms involved in the maintenance of intracellular concentration of Cl- that differs from concentration equilibrium have been considered. This review provides the biochemical properties of the GABA(A) coupled Cl-/HCO3(-)-ATPase which is a candidate for an novel primary active system in neuronal membranes. Special emphasis has been placed on a review of the prerequisites for the existence of the GABA(A)-coupled ATPase. This work provides data for the benefit not only functional but also the alleged structural coupling of the enzyme with GABA(A)-receptors. It is concluded on the importance of the found ATPase in primary active transport processes across the plasma membrane of neuronal cells with different level of the organization. PMID- 26155668 TI - [Paleoamygdala as the Neuroendocrine Center of Regulation of Reproductive Processis]. AB - This review contains modern information about the representation of serotoninergic system in the Amygdala with detailed characteristics of the localization of serotonine fibers and serotonine receptors in nuclear and paleocortical structures. These data indicate the joint participation of serotonine and sex steroids in the regulation of the neuroedocrine function of Amygdala, which have a modulating effect on the secretion and release gonadotropine centers and sexual behavior centers in the hypothalamic area of the brain. The survey also gives information about changes in the exchange of serotonine in the Amygdala's structures in the process of alimentary, maternal, aggressive-defensive and emotional behavior. Systematizes the data on the role of serotonin and sex steroids in the mechanisms involved in the stress response of Amygdala, and its participation in the formation of mood, emotions and the genesis of depression. Presented data on changes in morphometric characteristics of brain structures caused by polymorphic variants of genes of serotoninergic systems and data on the asymmetry of its content. PMID- 26155669 TI - [Vascular endothelial Barrier Function]. AB - Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability. PMID- 26155670 TI - Identification and glycobiological characterization of circulating immune complexes in patients with visceral leishmaniasis and post kala azar dermal leishmaniasis. AB - Here, we investigated the quantitative and qualitative differences in antibody classes and subclasses in serum immune complexes (ICs) of Visceral Leishmaniasis (VL), Post Kala-azar Dermal Leishmaniasis (PKDL) and different cross reactive diseases like Malaria, Leprosy, Vitiligo as compared to control subjects. IC levels were measured through a newly developed PEG ELISA, using L. donovani promastigote membrane antigen coated plate. Antibody classes and subclasses were identified using polyspecific sera and monoclonal antibodies, respectively. ICs were purified using polyethylene glycol (PEG) precipitation. Conditional logistic regression showed an association between IgG1-containing ICs and increased risk of PKDL (OR = 75, P < 0.05) and an association of IgG-containing ICs with VL (OR = 621, P = 0.001). PEG ELISA demonstrated almost 13-15 fold higher IgG containing ICs titers in VL as compared to control (P < 0.001). The assay further established a significant (P < 0.05) difference in the IgG containing ICs titers between VL and PKDL. The isolated ICs were further analyzed by subjecting them to one-dimensional PAGE and subsequently stained with combination of periodic acid schiff (PAS) with silver. A differential banding pattern between VL and PKDL was obtained. Four distinct bands with carbohydrate rich glycoconjugates were identified in PKDL ICs, which were absent in VL and control group. It suggests the scope for developing a novel differential diagnostic assay. PMID- 26155671 TI - Down-regulation of osmotin (PR5) gene by virus-induced gene silencing (VIGS) leads to susceptibility of resistant Piper colubrinum Link. to the oomycete pathogen Phytophthora capsici Leonian. AB - Piper colubrinum Link., a distant relative of Piper nigrum L., is immune to the oomycete pathogen Phytophthora capsici Leonian that causes 'quick wilt' in cultivated black pepper (P. nigrum). The osmotin, PR5 gene homologue, earlier identified from P. colubrinum, showed significant overexpression in response to pathogen and defense signalling molecules. The present study focuses on the functional validation of P. colubrinum osmotin (PcOSM) by virus induced gene silencing (VIGS) using Tobacco Rattle Virus (TRV)-based vector. P. colubrinum plants maintained under controlled growth conditions in a growth chamber were infiltrated with Agrobacterium carrying TRV empty vector (control) and TRV vector carrying PcOSM. Three weeks post infiltration, viral movement was confirmed in newly emerged leaves of infiltrated plants by RT-PCR using TRV RNA1 and TRV RNA2 primers. Semi-quantitative RT-PCR confirmed significant down-regulation of PcOSM gene in TRV-PcOSM infiltrated plant compared with the control plants. The control and silenced plants were challenged with Phytophthora capsici which demonstrated that knock-down of PcOSM in P. colubrinum leads to increased fungal mycelial growth in silenced plants compared to control plants, which was accompanied by decreased accumulation of H2O2 as indicated by 3,3'-diaminobenzidine (DAB) staining. Thus, in this study, we demonstrated that Piper colubrinum osmotin gene is required for resisting P. capsici infection and has possible role in hypersensitive cell death response and oxidative burst signaling during infection. PMID- 26155672 TI - Isolation and gene expression analysis of Phospholipase C in response to abiotic stresses from Vigna radiata (L.) Wilczek. AB - Phosphatidylinositol (PtdIns) is a major phospholipid in eukaryotic cells. Many studies have revealed that the phosphoinositide (PI) signaling pathway plays an important role in plant growth and development. Phospholipase C (PLC) is reported to have a crucial role in the PI pathway. This work focuses on the isolation and investigation of PLC in response to abiotic stress factors in green gram. The PLC cDNA, designated VrPLC, encoding a protein of 591 amino acids was cloned and expressed in E. coli. The predicted isoelectric point (pI) and molecular weight were 5.96 and 67.3 kDa, respectively. The tertiary structure of the PLC was also predicted and found to be mainly composed of random coils. In addition, VrPLC expression analysis was performed under environmental stress and the results showed that the expression of VrPLC was rapidly induced in an abscisic acid independent manner in response to drought and salt stress. PLC expression was found to be up-regulated by SA and down-regulated by wound in leaf tissues; however, there was no significant difference in the expression of PLC in plants subjected to high temperature and H2O2. Our results suggest that a close link/relationship between PLC expression and stress responses in green gram. PMID- 26155673 TI - Indole acetic acid production by fluorescent Pseudomonas spp. from the rhizosphere of Plectranthus amboinicus (Lour.) Spreng. and their variation in extragenic repetitive DNA sequences. AB - Fluorescent Pseudomonas (FP) is a heterogenous group of growth promoting rhizobacteria that regulate plant growth by releasing secondary metabolic compounds viz., indole acetic acid (IAA), siderophores, ammonia and hydrogen cyanide. In the present study, IAA producing FPs from the rhizosphere of Plectranthus amboinicus were characterized morphologically, biochemically and at the molecular level. Molecular identification of the isolates were carried out using Pseudomonas specific primers. The effect of varying time (24, 48, 72 and 96 h), Trp concentrations (100, 200, 300, 400 and 500 MUg x ml(-1)), temperature (10, 26, 37 and 50 +/- 2 degrees C) and pH (6, 7 and 8) on IAA production by 10 best isolates were studied. Results showed higher IAA production at 72 h incubation, at 300 MUg x ml(-1) Trp concentration, temperature 26 +/- 2 degrees C and pH 7. TLC with acidified ethyl acetate extract showed that the IAA produced has a similar Rf value to that of the standard IAA. Results of TLC were confirmed by HPLC analysis. Genetic diversity of the isolates was also studied using 40 RAPD and 4 Rep primers. Genetic diversity parameters such as dominance, Shannon index and Simpson index were calculated. Out of 40 RAPD primers tested, 9 (2 OP-D series and 7 OP-E series) were shortlisted for further analysis. Studies using RAPD, ERIC, BOX, REP and GTG5 primers revealed that isolates exhibit significant diversity in repetitive DNA sequences irrespective of the rhizosphere. PMID- 26155674 TI - Phytase production through response surface methodology and molecular characterization of Aspergillus fumigatus NF191. AB - Phytase play an important role in phytic acid catalysis that act as a food inhibitor in cereals. Here, we isolated high phytase producing isolates NF191 closely related to Aspergillus fumigatus sp. from piggery soil. DNA was isolated from the fungal culture and amplified the ITS region using ITS1 and ITS4 primer using PCR. The 400-900 bp amplicon was gel eluted and subjected to sequencing. The sequencing results were assembled and compared with NCBI data base which showed the 99% identity of Aspergillus fumigatus. Different carbon sources viz., fructose, galactose, lactose, dextrose, sucrose, maltose and different nitrogen sources (organic & inorganic) NH4Cl, NH4NO3, (NH4)2SO4, KNO3, NaNO3, urea, yeast extract, peptone, beef extract were tested for optimal production. The 0.3% dextrose, 0.5% NH4NO3 and 96 h incubation time showed the best production and enzyme activity at 45 degrees C incubation temperature. The selected parameters, dextrose, ammonium sulphate and incubation time, when employed with statistical optimization approach involving response surface optimization using Box Behnken Design, gave a 1.3 fold increase in phytase production compared to unoptimized condition. PMID- 26155675 TI - Production of a cellulase-free alkaline xylanase from Bacillus pumilus MTCC 5015 by submerged fermentation and its application in biobleaching. AB - Here, we described the production of a cellulase-free alkaline xylanase from Bacillus pumilus MTCC 5015 by submerged fermentation and its application in biobleaching. Various process parameters affecting xylanase production by B. pumilus were optimized by adopting a Plackett-Burman design (PBD) as well as Response surface methodology (RSM). These statistical methods aid in improving the enzyme yield by analysing the individual crucial components of the medium. Maximum production was obtained with 4% yeast extract, 0.08% magnesium sulphate, 30 h of inoculum age, incubation temperature of 33.5 degrees C and pH 9.0. Under optimized conditions, the xylanase activity was 372 IU/ml. Media engineering improved a 5-fold increase in the enzyme production. Scanning electron microscopy (SEM) showed significant changes on the surface of xylanase treated pulps as a result of xylan hydrolysis. Increased roughness of paper carton fibres was apparent in scanning electron micrograph due to opening of the micro fibrils present on the surface by xylanase action. The untreated pulp did not show any such change. These results demonstrated that the B. pumilus MTCC 5015 xylanase was effective in bio-bleaching of paper carton. PMID- 26155676 TI - Bioprocess development for docosahexaenoic acid from novel fungal isolate of Fusarium solani. AB - Fungal cultures were isolated from soil samples collected from the Western Ghats regions of Kerala. Primary screening of isolated strains were done by Sudan black staining method and 15 lipid producing cultures were isolated. The fatty acid profiling of the positive strains were analyzed for docosahexaenoic acid (DHA) production. Selected oleaginous cultures were grown in submerged culture condition to study the biomass yield and poly unsaturated fatty acid, DHA production. The optimization of production process under submerged conditions was carried out using statistical experimental design and confirmation of DHA was done by GC analysis. Maximum DHA production of 150 mg/l was achieved on 4 days of incubation at submerged condition in the presence of glucose as carbon source. PMID- 26155677 TI - Phlorotannins from Brown Algae: inhibition of advanced glycation end products formation in high glucose induced Caenorhabditis elegans. AB - Advanced Glycation End products (AGE) generated in a non enzymatic protein glycation process are frequently associated with diabetes, aging and other chronic diseases. Here, we explored the protective effect of phlorotannins from brown algae Padina pavonica, Sargassum polycystum and Turbinaria ornata against AGEs formation. Phlorotannins were extracted from brown algae with methanol and its purity was analyzed by TLC and RP-HPLC-DAD. Twenty five grams of P. pavonica, S. polycystum, T. ornata yielded 27.6 +/- 0.8 MUg/ml, 37.7 MUg/ml and 37.1 +/- 0.74 MUg/ml of phloroglucinol equivalent of phlorotannins, respectively. Antioxidant potentials were examined through DPPH assay and their IC50 values were P. pavonica (30.12 +/- 0.99 MUg), S. polycystum (40.9 +/- 1.2 MUg) and T. ornata (22.9 +/- 1.3 MUg), which was comparatively lesser than the control ascorbic acid (46 +/- 0.2 MUg). Further, anti-AGE activity was examined in vitro by BSA-glucose assay with the extracted phlorotannins of brown algae (P. pavonica, 15.16 +/- 0.26 MUg/ml; S. polycystum, 35.245 +/- 2.3 MUg/ml; T. ornata, 22.7 +/- 0.3 MUg/ml), which revealed the required concentration to inhibit 50% of albumin glycation (IC50) were lower for extracts than controls (phloroglucinol, 222.33 +/- 4.9 MUg/ml; thiamine, 263 MUg/ml). Furthermore, brown algal extracts containing phlorotannins (100 MUl) exhibited protective effects against AGE formation in vivo in C. elegans with induced hyperglycemia. PMID- 26155678 TI - Characterization and biological activities of extracellular melanin produced by Schizophyllum commune (Fries). AB - Melanins are enigmatic pigments produced by a wide variety of microorganisms including bacteria and fungi. Here, we have isolated and characterized extracellular melanin from mushroom fungus, Schizophyllum commune. The extracellular dark pigment produced by the broth culture of S. commune, after 21 days of incubation was recovered by hot acid-alkali treatment. The melanin nature of the pigment was characterized by biochemical tests and further, confirmed by UV, IR, EPR, NMR and MALDI-TOF Mass Spectra. Extracellular melanin, at 100 MUg/ml, showed significant antibacterial activity against Escherichia coli, Bacillus subtilis, Klebsiella pneumoniae and Pseudomonas fluorescens and antifungal activity against Trichophyton simii and T. rubrum. At a concentration of 50 MUg/ml, melanin showed high free radical scavenging activity of DPPH (2,2 diphenyl-1-picrylhydrazyl) indicating its antioxidant potential. It showed concentration dependent inhibition of cell proliferation of Human Epidermoid Larynx Carcinoma Cell Line (HEP-2). This study has demonstrated characterization of melanin from basidiomycetes mushroom fungus, Schizophyllum commune and its applications. PMID- 26155679 TI - Bioleaching of nickel from spent petroleum catalyst using Acidithiobacillus thiooxidans DSM- 11478. AB - The present work deals with optimization of culture conditions and process parameters for bioleaching of spent petroleum catalyst collected from a petroleum refinery. The efficacy of Ni bioleaching from spent petroleum catalyst was determined using pure culture of Acidithiobacillus thiooxidans DSM- 11478. The culture conditions of pH, temperature and headspace volume to media volume ratio were optimized. EDX analysis was done to confirm the presence of Ni in the spent catalyst after roasting it to decoke its surface. The optimum temperature for A. thiooxidans DSM-11478 growth was found to be 32 degrees C. The enhanced recovery of nickel at very low pH was attributed to the higher acidic strength of sulfuric acid produced in the culture medium by the bacterium. During the bioleaching process, 89% of the Ni present in the catalyst waste could be successfully recovered in optimized conditions. This environment friendly bioleaching process proved efficient than the chemical method. Taking leads from the lab scale results, bioleaching in larger volumes (1, 5 and 10 L) was also performed to provide guidelines for taking up this technology for in situ industrial waste management. PMID- 26155680 TI - Phosphorus amendment competitively prevents chromium uptake and mitigates its toxicity in Spinacea oleracea L. AB - In this study, we assessed the role of phosphorus in preventing chromium uptake by plants. Two-factor complete randomized pot experiment (5x5 pattern) was conducted hydroponically with Spinacea oleracea L. (spinach), for 28 days in green house. Five concentrations of Cr (2.0, 3.5, 5.0, 6.5 and 8.0 mM), each amended with five concentrations of phosphorus (25, 50, 75, 100 and 125 mM) were supplied. With the phosphorus amendment in the growth medium, accumulation of chromium decreased up to 55% in root and 50% in shoot tissues. A 1.8-fold enhancement in total chlorophyll and 2-fold increase in the biomass of root and shoot were observed due to phosphorus amendment. Levels of superoxide dismutase, catalase, peroxidase and malondialdehyde were reduced by 27, 11.7, 38.1 and 45.5% in root tissues; and 27, 17.4, 32.3 and 35.1%, in shoot tissues, respectively. In conclusion, the phosphorus amendment has been shown not only to moderate the Cr toxicity in S. oleracea but also enrich chlorophyll content as well as the biomass. PMID- 26155681 TI - Differential effect of soil and environment on metabolic expression of turmeric (Curcuma longa cv. Roma). AB - Curcuma longa (Zingiberaceae) is known for its uses in medicine, cosmetics, food flavouring and textile industries. The secondary metabolites of turmeric like essential oil, oleoresin and curcumin are important for its multipurpose uses. These traits of turmeric vary from place to place due to the influence of environment, soil and agro-climatic conditions. Here, we analyzed turmeric from different agroclimatic regions for influence of various factors on its growth and yield of important phytochemicals. A high curcumin yielding cultivar i.e., Roma was collected from high altitude research station, Koraput (HARS) and planted in nine agroclimatic regions of Odisha. Analysis of soil texture, pH, organic carbon, micro and macro nutrients were done from all the studied zones up to 2nd generation. Plants grown in their released station i.e., Eastern Ghat High Land showed 5% of curcumin and were taken as control. Plants grown in different agroclimatic zones showed a range of 1.4-5% of curcumin and 0.3-0.7% of rhizome essential oil and 0.3-1% of leaf essential oil content. Gas chromatography and mass spectra analysis showed tumerone and alpha phellandrene as the major compounds in all the zones with 10-20% variation. The present study will be immensely helpful for standardization and management of environmental and ecological factors for high phytochemical yield in turmeric plant. PMID- 26155682 TI - Diversity of Drimia indica (Roxb.) Jessop and its relationship to Drimia nagarjunae using phenotypic traits and molecular markers. AB - In the present study, we explored the diversity of different accessions of Drimia indica and its relation to D. nagarjunae using phenotypic traits and molecular markers. Twenty populations of D. indica, from different parts of India, were compared with D. nagarjunae, an endangered medicinal plant collected from Andhra Pradesh, India. Two species showed appreciable phenotypic diversity in number of leaves, leaf indices, bulb circumference, bulb length and length of roots. The principal component analysis (PCA) performed on above 5 quantitative characters to determine relationship among populations, has distinguished D. nagarjunae from D. indica phenotypically. Genetic diversity was analysed using RAPD and ISSR primers which produced reproducible bands in 8 RAPD and 3 ISSR primers. A total of 89 amplicons were observed, of which 69 (77.53%) were polymorphic. Cluster diagram and phylogenetic linkage showed that D. nagarjunae formed a separate cluster, showing no similarity with any of the populations of D. indica. The molecular marker data correlated with PCA of phenotypic traits. Current investigations have demonstrated that the statistical approach for phenotypic characters and molecular markers analysis can be applied to study diversity in Drimia species. PMID- 26155683 TI - Comparative assessment of bacterial diversity associated with co-occurring eukaryotic hosts of Palk Bay origin. AB - Epibacterial communities of co-occurring eukaryotic hosts of Palk Bay origin (five seaweed species (Gracilaria sp, Padina sp, Enteromorpha sp, Sargassum sp, and Turbinaria sp) and one seagrass [Cymodaceae sp]) were analyzed for diversity and compared using 16S rRNA based Denaturant Gradient Gel Electrophoresis analysis. Diversity index revealed that Turbinaria sp hosts highest bacterial diversity while it was least in Gracilaria sp. The DGGE band profile showed that the epibacterial community differed considerably among the studied species. Statistical assessment using cluster analysis and Non-metric multidimensional scale analysis also authenticated the observed variability. Despite huge overlap, the composition of bacterial community structure differed significantly among the three closely related species namely Sargassum, Turbinaria and Padina. In addition, Enteromorpha and Sargassum, one being chlorophyta and the other phaeophyta showed about 80% similarity in bacterial composition. This differs from the general notion that epibacterial community composition will vary widely depending on the host phyla. The results extended the phenomenon of host specific epibacterial community irrespective of phylogeny and similarity in geographical location. PMID- 26155684 TI - Seeking Solutions on Tower Workers' Safety. PMID- 26155685 TI - Significant Revisions to OSHA 29 CFR 1910.269. AB - The updated OSHA 29 CFR 1910.269 requirements are significant for assisting employers in their efforts to protect their employees from electrical hazards. In addition, OSHA based these revisions on the latest consensus standards and improvements in electrical safety technology. Together, the updated regulation creates a unified and up-to-date set of requirements to help employers more effectively establish safe work practices to protect their workers. PMID- 26155688 TI - Safety Needs a Brand! PMID- 26155686 TI - Guide to Selecting the Right Ear Muff. PMID- 26155689 TI - Safety Incentive Programs Work. PMID- 26155690 TI - AED Macroeconomics 101: A Shifting Demand Curve. PMID- 26155691 TI - Chain of Survival Starts with Awareness and Preparedness. PMID- 26155692 TI - Keeping Oil and Gas Workers Safe and Avoiding Costly Penalties. PMID- 26155693 TI - Is Dialing 911 for Confined Space Rescue Right for the Oil and Gas Industry? PMID- 26155694 TI - A Safer Moving Experience. PMID- 26155695 TI - OSHA's Revised Recordkeeping Rule: Major Implications on Employers. PMID- 26155696 TI - DOT Driver Training Requirements. PMID- 26155697 TI - Teaming Up Against Heat Hazards. PMID- 26155698 TI - Tips for Protecting Construction Workers' Eyes in the Summer. PMID- 26155699 TI - The Most Important Issue of Your Vision Protection Program. PMID- 26155700 TI - Keeping Employees' Emergency Skills Current. PMID- 26155701 TI - Do You Really Know Your Safety Culture? PMID- 26155702 TI - Three Essentials for Elevating Safety Culture. PMID- 26155703 TI - [THE PROBLEM OF HEMORRHAGIC COMPLICATIONS OF PERCUTANEOUS CORONARY INTERVENTIONS IN ELDERLY PATIENTS WITH ACUTE CORONARY SYNDROME]. AB - The authors review the literature on the frequency of hemorrhagic complications of percutaneous coronary interventions with special reference to the patients of advanced age. PMID- 26155704 TI - [MENETRIER DISEASE]. AB - Menetrier disease (MD) is a very rare stomach pathology of unknown etiology characterized by manifest hypertrophy of gastric mucosa. The main causes of MD are believed to be Helicobacter pylori and cytomegalovirus infections. The most frequent symptom is epigastric pain. Also common are peripheral oedema due to hypoalbuminemia and increased permeability of gastric mucosa. The main diagnostic signs of MD include diffusive enhancement of mucosal folds, foveolar hyperplasia and glandular atrophy with a decrease in the number of main and parietal cells, hypoalbuminemia and peripheral oedema. MD being a very rare condition, the optimal methodfor its treatment is unknown. PMID- 26155705 TI - [IMMUNOMODULATORS IN THE TREATMENT AND PREVENTION OF HERPES VIRUS INFECTIONS]. AB - Herpes virus infections cause disbalance of the interferon system, suppress cellular andphagocytic reactions. This paper deals with modern classifications of immunomodulators and substantiates their application for the treatment of viral infections. Also, it demonstrates high efficacy of cycloferon as an additional agent for the treatment and prevention (immunorehabilitation) of recurrent genital herpes. Cycloferon exerts antiviral and immunomodulating action, does not interact with other medications, and is fairly well tolerated by the patients. PMID- 26155706 TI - [MODERN STRATEGY FOR THE TREATMENT OF PATIENTS WITH "HIBERNATING MYOCARDIUM"]. AB - The paper reports results of endovascular treatment of 66 patients with post infarction cardiosclerosis. It was shown that normalization of coronary circulation in patients with viable hibernating myocardium in the zone of the affected artery not only eliminates the signs of chronic ischemia and slows down post-infarction heart remodeling but also restores the lost functions of hibernating myocardium which has beneficial influence on prognosis of the disease. Functioning of hibernating myocardium depends on the timely restoration of coronary circulation. PMID- 26155707 TI - [SECONDARY PREVENTION OF ARTERIAL HYPERTENSION IN VEHICLE DRIVERS--EFFICIENCY, SPECIFIC SAFETY]. AB - AIM: To estimate effectiveness and safety of pharmacotherapy in vehicle drivers with arterial hypertension (AH). MATERIALS AND METHODS: 432 patients with grade I III AH including 82 with cardiovascular complications largely of II and III grade were under observation during 2.5-4 months using clinical and instrumental methods (24hr AP & ECG monitoring) as well as psychophysiological testing (PPT). RESULTS: Ramipril and atenolol were efficient in 77.4 and 91.6% of the cases respectively; side effects were documented in 23.9 and 10.9%, somnolence and apathy in 13%, signs of somnolence in 2.2% of the cases. PPT revealed deterioration of the ability to drive (p < 0.05) in the patients given rampiril and the absence of its change in those receiving atenolol. Teveten (eprosartan) and diroton (lisinopril) were efficient in 94.8 and 81% of the cases but 8.6% of the patients refused to continue therapy because of side effects, such as somnolence, dry cough. Diroton deteriorated results of PPT (p < 0.05) and teveten improved them (p < 0.01). The effectiveness of isradipine (lomir), clophiline, estulic and trandolapril was 93.7, 7-87.5, 5-81.2, 2-82%. Isradipine had beneficial effect on PPT results (p= 65 years old) use up to 30% of all commonly prescribed medication, and they suffer more their adverse effects than the general population. In order to minimize this risk, physicians should avoid polypharmacy, dangerous pharmacological interactions and take into account pharmacodynamic and senile pharmacokinetic changes before prescribing any medication to the elderly. The present review article originally describes how renal physiology changes secondary to aging such as dysautonomia, glomerular filtration rate reduction, tubular back-filtration, sodium, calcium and magnesium loss, potassium retention, altered dilution-concentration capability, tubular frailty, genetics, internal milieu and body composition are senile changes that when combined predispose elderly people to suffer from pharmacological adverse effects. Knowledge of these physiological modifications associated with aging and their impact on the pharmacology of particular drugs may help to optimize drug use and to avoid complications in this age group. PMID- 26155720 TI - Tri-layered chitosan scaffold as a potential skin substitute. AB - A tri-layered chitosan-based scaffold was successfully made to replicate the striation of a full-thickness skin more accurately than a single- or bi-layered scaffold, which needed weeks of co-culturing of fibroblasts and keratinocytes to achieve similar striation. Chitosan solution was freeze-dried and made into porous disks. Chitosan or chitosan-pectin in acetic acid solution was electrospun onto the chitosan disk to form a nanofibrous layer and a thin film. Examinations based on scanning electron spectroscopy showed that the scaffold was composed of a porous layer (2 mm) to simulate the dermis, a thin film (25-45 MUm) to mimic the basement membrane, and a layer of nanofibers (100-200 MUm) to serve as the protective epidermis. The tensile strength and modulus of the composite scaffold were significantly higher than those of the chitosan disk (p < 0.01). The composite was able to quickly absorb water and stayed intact throughout the course of the 14-day cell culture tests. The fibroblast cells seeded on both sides of the scaffolds were able to proliferate and stayed separated by the thin film. PMID- 26155721 TI - Simultaneous Observation of Cells and Nuclear Tracks from the Boron Neutron Capture Reaction by UV-C Sensitization of Polycarbonate. AB - The distribution of boron in tissue samples coming from boron neutron capture therapy protocols can be determined through the analysis of its autoradiography image on a nuclear track detector. A more precise knowledge of boron atom location on the microscopic scale can be attained by the observation of nuclear tracks superimposed on the sample image on the detector. A method to produce an "imprint" of cells cultivated on a polycarbonate detector was developed, based on the photodegradation properties of UV-C radiation on this material. Optimal conditions to generate an appropriate monolayer of Mel-J cells incubated with boronophenylalanine were found. The best images of both cells and nuclear tracks were obtained for a neutron fluence of 1013 cm-2, 6 h UV-C (254 nm) exposure, and 4 min etching time with a KOH solution. The imprint morphology was analyzed by both light and scanning electron microscopy. Similar samples, exposed to UV-A (360 nm) revealed no cellular imprinting. Etch pits were present only inside the cell imprints, indicating a preferential boron uptake (about threefold the incubation concentration). Comparative studies of boron absorption in different cell lines and in vitro evaluation of the effect of diverse boron compounds are feasible with this methodology. PMID- 26155722 TI - A Review of Guidelines for the Primary Prevention of Legionellosis in Long-Term Care Facilities. AB - Legionellosis is an important public health problem in the United States and other countries, and residents of long-term care facilities (LTCFs) are at higher risk for Legionnaires' disease than the general population. In this study, we reviewed published US and international guidelines for the primary prevention of legionellosis in LTCFs, including nursing homes, skilled nursing facilities, assisted living facilities, and aged care facilities. The results of this review indicate that most guidelines emphasize adequate design and maintenance of water systems and water temperatures; however, guidance regarding routine preventative environmental testing for Legionella bacteria is not uniform among various jurisdictions, and facilities are generally left without clear guidance on this issue. In the United States, the Centers for Disease Control and Prevention does not recommend such testing in LTCFs, in contrast to the Veterans Health Administration and Environmental Protection Agency. Internationally, the World Health Organization recommends routine environmental testing, as do Ireland; France; The Netherlands; South Africa; Vienna, Austria; and Queensland, Australia. Among domestic and international guidelines in favor of environmental testing, recommendations on the frequency of testing for Legionella in water systems vary. Further research to inform recommendations on the usefulness of routine environmental testing and other measures for the primary prevention of legionellosis in this setting is needed. PMID- 26155723 TI - Daily (In)Activities of Nursing Home Residents in Their Wards: An Observation Study. AB - OBJECTIVES: Research shows that nursing home residents are largely inactive. This inactivity negatively influences physical fitness, and participation in daily activities is known to have a positive influence on physical function and quality of life. Existing research does not provide sufficient insight into the daily activities in which nursing home residents participate. This insight is needed to develop future interventions so as to encourage nursing home residents to participate in daily activities and, thereby, decrease inactivity. The purpose of this study was to obtain insight into daily (in)activities of psychogeriatric and somatic nursing home residents during the day and their body positions during these (in)activities. DESIGN: Cross-sectional observation study. SETTING: Nursing homes in the Netherlands (19 psychogeriatric and 11 somatic wards). PARTICIPANTS: Participants were 723 home residents in 7 nursing homes. MEASUREMENTS: Observations were conducted using a self-developed observation list. Residents were observed in their wards during 5 random observation times between 7:00 am and 11:00 pm, in which the daily activity and position of the resident during this activity were scored. Percentages of activities and positions were calculated for each observation time. RESULTS: In total, 3282 observations (91% of the intended 3615 observations) were conducted. Nursing home residents of both psychogeriatric and somatic wards were mainly observed partaking in in activities, such as sleeping, doing nothing, and watching TV (range: 45%-77% of the 5 observation times). Furthermore, residents were engaged in activities of daily living (ADLs) (range: 15%-38%) that mainly comprised activities related to mobility (range: 10%-19%) and eating and drinking (range: 2%-17%). Engagement of residents in instrumental ADLs (IADLs) was rarely observed (up to 3%). Residents were largely observed in a lying or sitting position (range: 89%-92%). CONCLUSION: Most of the psychogeriatric and somatic nursing home residents spend their day inactive in a lying or sitting position in the ward. To encourage nursing home residents in daily activities in the wards, interventions are needed that (1) focus on increasing ADLs and IADLs, and (2) encourage standing and walking. PMID- 26155724 TI - Tissue Characterization of Coronary Plaques as a Key to Reno-Cardiac Syndrome. PMID- 26155726 TI - In vitro, fluorescence-quenching and computational studies on the interaction between lipoxygenase and 5-hydroxy-3',4',7-trimethoxyflavone from Lippia nodiflora L. AB - Lippia nodiflora L. is extensively used in traditional medicine for several medicinal purposes, including their use in inflammatory disorders. In this study, the folk use of L. nodiflora was validated using the isolated natural compound, 5 hydroxy-3',4',7-trimethoxyflavone (HTMF) by in vitro, fluorescence spectroscopic and molecular modeling studies with lipoxygenase (LOX), because LOX plays an essential role in inflammatory responses. In this perspective, the methanol extract and HTMF are shown to demonstrate prominent inhibitory activity against soybean lipoxygenase, with an IC50 value of 21.12 and 23.97 ug/ml, respectively. The data obtained from the spectroscopic method revealed that the quenching of intrinsic fluorescence of LOX is produced as a result of the complex formation of LOX-HTMF. The binding mode analysis of HTMF within the LOX enzyme suggested that hydrogen bond formation, hydrophobic interaction and pi-pi stacking could account for the binding of HTMF. Molecular dynamics results indicated the interaction of HTMF with LOX and the stability of ligand-enzyme complex was maintained throughout the simulation. The computational results are reliable with experimental facts and provided a good representation for understanding the binding mode of HTMF inside the active site of lipoxygenase enzyme. PMID- 26155725 TI - Neuropsychological Performance in Polyconsumer Men Under Treatment. Influence of Age of Onset of Substance Use. AB - Neurocognition is a key factor in the development and maintenance of Substance Use Disorders (SUD). However, there are still several aspects that need to be studied in this area. In this study, we elucidate the influence of age of onset of substance use (OSU) on the clinical course and neuropsychological performance of substance use disorder (SUD) patients, as well as to explore the influence of years of education, duration of drug use and premorbid intelligence quotient (IQ) on the cognitive results obtained. An exhaustive neuropsychological battery was used to assess different cognitive domains in 80 male polyconsumers, 41 with earlier OSU (16 years or before: OSU <= 16) and 39 with later OSU (17 years or later: OSU >= 17). The patients were under treatment with at least 4 months of abstinence confirmed by urinalysis. The OSU <= 16 group presented a worse clinical state, as well as a lower premorbid IQ and worse performance in processing speed, visual perception and planning skills. The duration of drug use may account for the differences in planning and processing speed. In this work we discuss the premorbid or acquired nature of the cognitive deficits found. PMID- 26155727 TI - Preface. Ethics and Responsible Conduct of Research within the Chemical Community. Ideas and Experiences Worth Sharing. PMID- 26155728 TI - Foreword. PMID- 26155729 TI - Ethics in Science: The Unique Consequences of Chemistry. AB - This article discusses the ethical issues unique to the science and practice of chemistry. These issues arise from chemistry's position in the middle between the theoretical and the practical, a science concerned with molecules that are of the right size to directly affect human life. Many of the issues are raised by the central activity of chemistry--synthesis. Chemists make thousands of new substances each year. Many are beneficial, but others are threats. Since the development of the chemical industry in the nineteenth century, chemistry has contributed to the deterioration of the environment but has also helped to reduce pollution. Finally, we discuss the role of codes of ethics and whether the current codes of conduct for chemists are adequate for the challenges of today's world. PMID- 26155730 TI - Tension in Chemistry and Its Contents. AB - This article makes a case for a positive role of tension in the creative process in chemistry. I begin with an argument that there is an inherent tension in what makes molecules interesting--their positioning along various polar axes. One of these, the age-old differentiation between useful (to society and for personal profit) commercialization and pure understanding of molecules and their reactions is characteristic. The question of whether there are any bad molecules then leads me to ethical concerns in chemistry, and a particular working out of these in interactions of chemists in the Middle East. An analysis is made of the special tensions involved in publishing, especially in citation ethics; chemists publish a lot, so this is situation ethics worked out on a daily basis. I then find in the literature of psychology good evidence for the positive value of moderate stress in stimulating creativity. It is obvious that too much tension leads to distress, and there are some institutional aspects of chemistry that do not come out well here. But all in all, the dynamic middle is alive, and it leads to good new science. PMID- 26155731 TI - Authorship Issues and Conflict in the U.S. Academic Chemical Community. AB - A survey on credit issues and related "responsible conduct of research" (RCR) behaviors was conducted with academic chemists in Ph.D. granting institutions in the U.S. Six hundred faculty members responded. Fifty percent of the respondents reported not receiving appropriate credit for contributions they had made to projects the results of which had been published, including when they themselves were students. Thirty percent of these individuals discussed this lack of credit with the "offending" individual, and as a consequence of those discussions, a small percentage of individuals were provided either co-authorship or an acknowledgment. The majority who did not enter into a discussion with the "offending" individual reported two primary reasons for not doing so: that they "could not imagine any good coming from such a conversation" and "I was afraid of being in a compromised situation." A discussion of relationship asymmetry in the academic setting is provided. Confronting one's colleague regarding credit is compared with whistleblowing, and the possible consequences of blacklisting are discussed. A number of recommendations for minimizing authorship disputes are provided. PMID- 26155732 TI - Ethics and the Responsible Conduct of Research in the Chemical Community: The Unique Role and Challenges of the News Media. AB - Journalists who cover scientific research, including chemistry research, have an obligation to report on alleged cases of research misconduct when knowledge of these surface. New Government definitions of research misconduct, beginning in the late 1990s with the Clinton Administration, have helped scientists, policymakers, as well as journalists sort out and make sense of alleged research misconduct. Journalistic reporting on research misconduct includes many challenges: gathering information from sources who are intimidated or afraid to speak, strict adherence to journalist ethics that take on a new dimension when careers, reputations, and research funding are at stake; efforts by government and institutional bureaucrats to dampen or thwart legitimate news coverage. The Internet, blogging, and social media have added still more complexity and ethical quandaries to this blend. The author, News Editor of Chemical & Engineering News published by the American Chemical Society, provides examples from his own career and that of colleagues. He suggests that an enhanced spirit of understanding and cooperation between journalists and members of the scientific community can lead to avenues of open discussion of research misconduct--discussions that might prevent and mitigate the very real damage caused by bad actors in science who betray themselves, their peers, and the body of modern day scientific knowledge when they make the decision to march into the darkness of dishonesty, plagiarism, or falsification. PMID- 26155733 TI - Social Media, Peer Review, and Responsible Conduct of Research (RCR) in Chemistry: Trends, Pitfalls, and Promises. AB - Over the last two decades, various themes inherent in the responsible conduct of research (RCR) in chemistry have been brought to light through prominent cases of research misconduct. This article will describe a few of these cases especially through the lens of social media such as blogs and Twitter. A case will be made that these wholly novel modalities of online discussion are now complementing, and in some cases even circumventing some of the limitations of traditional peer review in chemistry. We present in detail our evaluation of three recent cases of RCR along with several other social media illustrations. These cases have been selected to be representative and showcase several of the most prominent issues at the intersection of traditional and social-media based peer review. In each case, basic details are presented along with a brief discussion of the underlying issues-readers interested in deeper analysis of each subject are referred to a collection of relevant articles and websites. This perspective focuses on the most important RCR issues that have arisen in the past decade, a time which we believe coincides with the serious participation of the scientific community in general, and the chemistry community in particular, in social media-based, citizen-enabled peer-review. A discussion of important trends in RCR in the age of social media, outstanding developments in this area, and questions of enduring interest for the near future concludes the article. PMID- 26155735 TI - Epigenetic events regulating monoallelic gene expression. AB - In mammals, generally it is assumed that the genes inherited from each parent are expressed to similar levels. However, it is now apparent that in non-sex chromosomes, 6-10% of genes are selected for monoallelic expression. Monoallelic expression or allelic exclusion is established either in an imprinted (parent-of origin) or a stochastic manner. The stochastic model explains random selection while the imprinted model describes parent-of-origin specific selection of alleles for expression. Allelic exclusion occurs during X chromosome inactivation, parent-of-origin expression of imprinted genes and stochastic monoallelic expression of cell surface molecules, clustered protocadherin (PCDH) genes. Mis-regulation or loss of allelic exclusion contributes to developmental diseases. Epigenetic mechanisms are fundamental players that determine this type of expression despite a homogenous genetic background. DNA methylation and histone modifications are two mediators of the epigenetic phenomena. The majority of DNA methylation is found on cytosines of the CpG dinucleotide in mammals. Several covalent modifications of histones change the electrostatic forces between DNA and histones modifying gene expression. Long-range chromatin interactions organize chromatin into transcriptionally permissive and prohibitive regions leading to simultaneous regulation of gene expression and repression. Non coding RNAs (ncRNAs) are also players in regulating gene expression. Together, these epigenetic mechanisms fine-tune gene expression levels essential for normal development and survival. In this review, first we discuss what is known about monoallelic gene expression. Then, we focus on the molecular mechanisms that regulate expression of three monoallelically expressed gene classes: the X-linked genes, selected imprinted genes and PCDH genes. PMID- 26155736 TI - Association of TCF7L2 Polymorphism with Diabetic Nephropathy in the South Indian Population. AB - The transcription factor 7-like 2 (TCF7L2) gene plays a significant role in the development of type 2 diabetes and diabetic nephropathy. The aim of this study was to investigate the association of TCF7L2 rs12255372 (G/T)polymorphism with type 2 diabetic nephropathy in the South Indian population. A total of 2102 subjects, 927 normal glucose tolerant (NGT) subjects, 598 type 2 diabetic subjects without nephropathy (DM), and 577 type 2 diabetic subjects with nephropathy (DN) were genotyped by MassARRAY. As compared to the NGT group, the odds ratio (adjusted for age, sex, BMI, HbA1c, and systolic BP) computed for the GT/TT genotype taking the GG genotype as reference was found to be 2.02 (95% CI: 1.16-3.51, p = 0.013) for DN and 1.94 (95% CI: 1.36-2.78, p = 0.0002) for DM. The genotype frequency was not significantly different between the DM and DN groups. In conclusion, the rs12255372 polymorphism in the TCF7L2 gene is associated with type 2 diabetes and DN but its association with DN is mediated through diabetes. PMID- 26155738 TI - A Barcoding Strategy Enabling Higher-Throughput Library Screening by Microscopy. AB - Dramatic progress has been made in the design and build phases of the design build-test cycle for engineering cells. However, the test phase usually limits throughput, as many outputs of interest are not amenable to rapid analytical measurements. For example, phenotypes such as motility, morphology, and subcellular localization can be readily measured by microscopy, but analysis of these phenotypes is notoriously slow. To increase throughput, we developed microscopy-readable barcodes (MiCodes) composed of fluorescent proteins targeted to discernible organelles. In this system, a unique barcode can be genetically linked to each library member, making possible the parallel analysis of phenotypes of interest via microscopy. As a first demonstration, we MiCoded a set of synthetic coiled-coil leucine zipper proteins to allow an 8 * 8 matrix to be tested for specific interactions in micrographs consisting of mixed populations of cells. A novel microscopy-readable two-hybrid fluorescence localization assay for probing candidate interactions in the cytosol was also developed using a bait protein targeted to the peroxisome and a prey protein tagged with a fluorescent protein. This work introduces a generalizable, scalable platform for making microscopy amenable to higher-throughput library screening experiments, thereby coupling the power of imaging with the utility of combinatorial search paradigms. PMID- 26155739 TI - The mycobacterial P55 efflux pump is required for optimal growth on cholesterol. AB - Cholesterol catabolism is thought to be a key factor contributing to the pathogenesis of Mycobacterium tuberculosis. Previous epistasis and mutant screening studies predicted that the P55 efflux pump (Rv1410c) positively interacts with the Mce4 transporter, a major cholesterol import system of M. tuberculosis and is needed for optimal growth in vitro, in macrophages, and in vivo. Using a combination of cell growth kinetic techniques, cholesterol consumption, and [4-(14)C]cholesterol uptake studies, we demonstrated that the Mycobacterium bovis BCG rv1410c gene indeed is needed for optimal in vitro growth on cholesterol and other carbon sources. Our data, together with previous predictions, support hypotheses that the P55 efflux pump functions in maintaining general metabolism or as a subunit of the Mce4 transport apparatus (catalyzing its assembly or providing cell wall integrity) to allow more efficient cholesterol uptake. PMID- 26155737 TI - Myosin light chains: Teaching old dogs new tricks. AB - The myosin holoenzyme is a multimeric protein complex consisting of heavy chains and light chains. Myosin light chains are calmodulin family members which are crucially involved in the mechanoenzymatic function of the myosin holoenzyme. This review examines the diversity of light chains within the myosin superfamily, discusses interactions between the light chain and the myosin heavy chain as well as regulatory and structural functions of the light chain as a subunit of the myosin holoenzyme. It covers aspects of the myosin light chain in the localization of the myosin holoenzyme, protein-protein interactions and light chain binding to non-myosin binding partners. Finally, this review challenges the dogma that myosin regulatory and essential light chain exclusively associate with conventional myosin heavy chains while unconventional myosin heavy chains usually associate with calmodulin. PMID- 26155741 TI - Characterization of the Sprint and Repeated-Sprint Sequences Performed by Professional Futsal Players, According to Playing Position, During Official Matches. AB - The purposes of this study were to investigate sprints and to characterize repeated-sprint sequences (RS) performed by athletes during professional futsal matches. We analyzed 97 players during 5 official matches using the DVideo automatic tracking system. The sprints were analyzed during the first and second halves according to playing position, and RS were categorized according to the number of sprints and the time between them. The results showed an increase (F[1, 2520] = 3.96; P = .046) in the sprint duration from the first (mean = 3.1 +/- 1.3) to the second half (mean = 3.2 +/- 1.2). However, no differences were found for other variables (distance covered, peak velocity, initial velocity, recovery time between sprints, and sprints performed per minute) or among playing positions. In addition, when considering RS, the results showed that RS comprising two sprints interspersed with a maximum of 15 seconds of recovery were significantly more frequent than other RS. The findings of this study characterizing the sprinting features of futsal players can help coaches to plan physical training and assessments according to the requirements of the sport. PMID- 26155740 TI - Screen of FDA-approved drug library identifies maprotiline, an antibiofilm and antivirulence compound with QseC sensor-kinase dependent activity in Francisella novicida. AB - Development of new therapeutics against Select Agents such as Francisella is critical preparation in the event of bioterrorism. Testing FDA-approved drugs for this purpose may yield new activities unrelated to their intended purpose and may hasten the discovery of new therapeutics. A library of 420 FDA-approved drugs was screened for antibiofilm activity against a model organism for human tularemia, Francisella (F.) novicida, excluding drugs that significantly inhibited growth. The initial screen was based on the 2-component system (TCS) dependent biofilm effect, thus, the QseC dependence of maprotiline anti-biofilm action was demonstrated. By comparing their FDA-approved uses, chemical structures, and other properties of active drugs, toremifene and polycyclic antidepressants maprotiline and chlorpromazine were identified as being highly active against F. novicida biofilm formation. Further down-selection excluded toremifene for its membrane active activity and chlorpromazine for its high antimicrobial activity. The mode of action of maprotiline against F. novicida was sought. It was demonstrated that maprotiline was able to significantly down-regulate the expression of the virulence factor IglC, encoded on the Francisella Pathogenicity Island (FPI), suggesting that maprotiline is exerting an effect on bacterial virulence. Further studies showed that maprotiline significantly rescued F. novicida infected wax worm larvae. In vivo studies demonstrated that maprotiline treatment could prolong time to disease onset and survival in F. novicida infected mice. These results suggest that an FDA-approved drug such as maprotiline has the potential to combat Francisella infection as an antivirulence agent, and may have utility in combination with antibiotics. PMID- 26155742 TI - Staying in the 'sweet spot': A resilience-based analysis of the lived experience of low-risk drinking and abstention among British youth. AB - OBJECTIVE: The aim of this study was to understand how and why young people drink less or not at all when with their peers. Understanding the subjective experiences of moderate or non-drinkers may help identify protective processes facilitating resilience to cultural norm and influences that encourage excessive alcohol consumption among young people. DESIGN: Semi-structured interviews were conducted with 25 moderate- or non-drinkers aged 17-25 years (13 young women) living in South East England. Interviews explored recent experiences of social situations and encounters that did or did not involve alcohol. Transcripts were analysed using Interpretative Phenomenological Analysis. RESULTS: Analysis identified six conceptually coherent themes clustering within a superordinate theme of a healthy experience of moderate alcohol use or abstention: 'the sweet spot'. These themes were: feeling good in the body, feeling like you can be who you are, feeling like you belong, making a free choice, enjoying the moment, and feeling safe and secure. CONCLUSIONS: This resilience-based analysis showed how non-drinking and moderate-drinking may be experienced as a positive and proactive choice. Understanding the subjective experiences of young people may aid development of specific, realistic interventions to promote moderate drinking and abstention among young people in drinking cultures. PMID- 26155743 TI - Saprochaete capitata as an emerging fungus among patients with haematological malignencies. AB - Saprochaete capitata is a very rare pathogen that causes invasive disease particularly in patients with haematological malignancies. We recognised a clustering of S. capitata fungaemia in recent years. So, we report our 6-year surveillance study of fungaemia among patients with haematological malignancies and haematopoietic stem cell transplant. We performed a retrospective and observational study. Hospitalised patients aged >18 years with haematological malignancies were included in the study. A total of 51 fungaemia episodes of 47 patients were analysed. The characteristics of fungaemia in patients with S. capitata compared to patients with candidemia. Median duration of neutropenia was 21.5 days in patients with S. capitata fungaemia, whereas this duration was significantly shorter in patients with candidemia (8 days). Interval between first and last positive culture was significantly longer in patients with S. capitata fungaemia (P < 0.05). Previous use of caspofungin was significantly more common in patients with S. capitata fungaemia. Thirty-day mortality was found 40% for patients with candidemia, whereas it was 39% for patients with S. capitata. In conclusion, despite its limitations this study showed that a novel and more resistant yeast-like pathogen become prevalent due to use of caspofungin in patients with long-lasting neutropenia which was the most noteworthy finding of this 6-year surveillance study. PMID- 26155744 TI - Specific serum IgG at diagnosis of Staphylococcus aureus bloodstream invasion is correlated with disease progression. AB - Although Staphylococcus aureus is a prominent cause of infections, no vaccine is currently available. Active vaccination relies on immune memory, a core competence of the adaptive immune system. To elucidate whether adaptive immunity can provide protection from serious complications of S. aureus infection, a prospective observational study of 44 patients with S. aureus infection complicated by bacteremia was conducted. At diagnosis, serum IgG binding to S. aureus extracellular proteins was quantified on immunoblots and with Luminex based FLEXMAP 3DTM assays comprising 64 recombinant S. aureus proteins. Results were correlated with the course of the infection with sepsis as the main outcome variable. S. aureus-specific serum IgG levels at diagnosis of S. aureus infection were lower in patients developing sepsis than in patients without sepsis (P<0.05). The pattern of IgG binding to eight selected S. aureus proteins correctly predicted the disease course in 75% of patients. Robust immune memory of S. aureus was associated with protection from serious complications of bacterial invasion. Serum IgG binding to eight conserved S. aureus proteins enabled stratification of patients with high and low risk of sepsis early in the course of S. aureus infections complicated by bacteremia. SIGNIFICANCE: S. aureus is a dangerous pathogen of ever increasing importance both in hospitals and in the community. Due to the crisis of antibiotic resistance, an urgent need exists for new strategies to combat S. aureus infections, such as vaccination. To date, however, all vaccine trials have failed in clinical studies. It is therefore unclear whether the adaptive immune system is at all able to control S. aureus in humans. The paper demonstrates the use of proteomics for providing an answer to this crucial question. It describes novel results of a prospective study in patients with S. aureus infection complicated by bloodstream invasion. Immune proteomic analysis shows that robust immune memory of S. aureus - reflected by strong serum IgG antibody binding to S. aureus antigens - is associated with clinical protection from sepsis. This lends support to the notion of a vaccine to protect against the most serious complications of S. aureus infection. Hence, the data encourage further efforts in vaccine development. PMID- 26155745 TI - Suppression of hyperinsulinaemia in growing female mice provides long-term protection against obesity. AB - AIMS/HYPOTHESIS: Hyperinsulinaemia is associated with obesity but its causal role in the onset of obesity remains controversial. In this study, we tested the hypothesis that transient attenuation of diet-induced insulin hypersecretion in young mice can provide sustained protection against obesity throughout adult life. METHODS: Using 'genetically humanised' mice lacking both alleles of rodent specific Ins1, we compared mice heterozygous for the ancestral insulin gene Ins2 with Ins2(+/+) controls. Female Ins1(-/-):Ins2(+/-) and Ins1(-/-):Ins2(+/+) littermates were fed chow or high-fat diet (HFD). Insulin secretion, metabolic health variables and body mass/composition were tracked for over 1 year. We examined islet function and adipose transcript levels of adipogenic, lipogenic and lipolytic genes at two time points. RESULTS: In control Ins1(-/-):Ins2(+/+) mice, HFD resulted in elevated fasting and glucose-stimulated insulin secretion between 8 weeks and 27 weeks of age. Hyperinsulinaemia was reduced by nearly 50% in Ins1(-/-):Ins2(+/-) mice during this period, without lasting adverse effects on glucose homeostasis. This corresponded with attenuated weight gain and adiposity. White adipose tissue from Ins1(-/-):Ins2(+/-) mice had fewer large lipid droplets, although transcriptional changes were not detected. Importantly, Ins1(-/-):Ins2(+/-) mice remained lighter than Ins1(-/-):Ins2(+/+) littermates despite reaching an equivalent degree of hyperinsulinaemia on HFD by 52 weeks. CONCLUSIONS/INTERPRETATION: These data demonstrate that attenuation of hyperinsulinaemia in young, growing female mice provides a long-lasting protection against obesity. This protection persists despite a late-onset emergence of hyperinsulinaemia in HFD-fed Ins1(-/-):Ins2(+/-) mice. Given the evolutionary conserved roles of insulin, it is possible that suppressing hyperinsulinaemia early in life may have far-reaching consequences on obesity in full-grown adult humans. PMID- 26155746 TI - Association of subclinical inflammation with deterioration of glycaemia before the diagnosis of type 2 diabetes: the KORA S4/F4 study. AB - AIMS/HYPOTHESIS: The role of biomarkers of subclinical inflammation in the early deterioration of glycaemia before type 2 diabetes is largely unknown. We hypothesised that increased levels of circulating proinflammatory biomarkers and decreased circulating adiponectin would be associated with 7 year increases of HbA(1c) in non-diabetic individuals. METHODS: This study was based on individuals who participated in the prospective Cooperative Health Research in the Region of Augsburg (KORA) S4 survey (1999-2001) and the 7 year follow-up KORA F4 (2006 2008) survey. Individuals with type 2 diabetes at baseline or with a diagnosis of diabetes in the period between both surveys were excluded, which left a sample of 850 men and women. Multivariable linear regression analyses were performed to assess associations among baseline values of leucocyte count and levels of acute phase proteins (high-sensitivity C-reactive protein [hsCRP], serum amyloid A [SAA] and fibrinogen), IL-6 and adiponectin with changes in HbA1c between baseline and follow-up. RESULTS: A high leucocyte count and high hsCRP, SAA and IL-6 levels were positively associated with changes in HbA(1c) after adjusting for age, sex, lifestyle factors and baseline HbA(1c). In contrast, the adiponectin level was inversely associated with changes in HbA(1c) (p value between <0.0001 and 0.020). The associations of leucocyte count and levels of hsCRP and SAA with HbA(1c) changes remained significant after additional adjustment for waist circumference and circulating lipids at baseline and for the 7 year change in waist circumference (p value between 0.004 and 0.045). CONCLUSIONS/INTERPRETATION: An elevated leucocyte count and elevated hsCRP and SAA were associated with early deterioration of glycaemia before the diagnosis of type 2 diabetes. These associations were largely independent of baseline abdominal adiposity and increases in waist circumference. PMID- 26155748 TI - Patient perceptions of risky drinking: Knowledge of daily and weekly low-risk guidelines and standard drink sizes. AB - BACKGROUND: Effective intervention for risky drinking requires that clinicians and patients know low-risk daily and weekly guidelines and what constitutes a "standard drink." The authors hypothesized that most patients lack this knowledge, and that education is required. METHODS: Following primary care visits, patients completed anonymous exit questionnaires that included the 3 Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questions, "How many drinks (containing alcohol) can you safely have in one day?" and questions about size, in ounces, of a standard drink of wine, beer, and liquor. Descriptive analyses were done in Stata. RESULTS: Of 1,331 respondents (60% female, mean age: 49.6, SD = 17.5), 21% screened positive on the AUDIT-C for risky drinking. Only 10% of those accurately estimated daily low-risk limits, with 9% accurate on weekly limits, and half estimated low-risk limits at or below guidelines. Fewer than half who checked "Yes" to "Do you know what a 'standard drink' is?" provided accurate answers for beer, wine, or liquor. Patients with a positive screen were twice as likely to say they knew what a standard drink is, but only a third gave accurate estimates. When asked about plans in the next month regarding change in drinking behavior, 23% with a positive AUDIT-C indicated they were at least considering a change. CONCLUSIONS: Most patients in primary care don't know specifics of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines for low-risk drinking. Exploring patient perceptions of low-risk guidelines and current drinking behavior may reveal discrepancies worth discussing. For risky drinkers, most of whom don't know daily and weekly low-risk guidelines or standard drink sizes, education can be vital in intervening. Findings suggest the need for detailed and explicit social marketing and communication on exactly what low-risk drinking entails. PMID- 26155747 TI - Circulating microRNAs and diabetes: potential applications in medical practice. AB - The explosive increase in the worldwide prevalence of diabetes over recent years has transformed the disease into a major public health concern. While diabetes can be screened for and diagnosed by reliable biological tests based on blood glucose levels, by and large there are no means of detecting at-risk patients or of following diabetic complications. The recent discovery that microRNAs are not only chief intracellular players in many biological processes, including insulin secretion and action, but are also circulating, has put them in the limelight as possible biological markers. Here we discuss the potential role of circulating microRNAs as biomarkers in the context of diabetes and its associated complications. PMID- 26155750 TI - Noninvasive estimation of central blood pressure and analysis of pulse waves by applanation tonometry. PMID- 26155749 TI - Upregulation of canonical transient receptor potential channel in the pulmonary arterial smooth muscle of a chronic thromboembolic pulmonary hypertension rat model. AB - Chronic ligation of the left main pulmonary artery (PA) results in pulmonary vascular remodeling and sustained vasoconstriction. This method has been used to generate a postobstructive pulmonary vasculopathy model to mimic severe chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to examine the cellular and molecular mechanisms underlying CTEPH and to provide evidence for potential treatments. The CTEPH rat model was induced by surgical left PA ligation (LPAL). Right ventricular systolic pressure (RVSP), lung histochemistry and plasma D-dimer measurements were carried out to evaluate the model. A fluorescence microscope was used to measure the basal intracellular Ca(2+) concentration ([Ca(2+)]i) and store-operated Ca(2+) entry (SOCE) in rat distal pulmonary arterial smooth muscle cells through a Fura-2 fluorescence-based method. The expression of the canonical transient receptor potential channel 1 (TRPC1) and TRPC6 was determined by western blotting and real-time quantitative PCR in isolated distal pulmonary arteries (PA). At the time points of 2 and 5 weeks postsurgery, the RVSP showed significant increases in the LPAL groups in comparison with the respective control groups. LPAL also led to right ventricular hypertrophy (RVH), distal pulmonary arterial remodeling in unobstructed territories and persistently higher plasma D-dimer levels. Increases of the basal [Ca(2+)]i and SOCE in LPAL were associated with a clear upregulation of TRPC1 and TRPC6 expression in the distal PA. Our study demonstrated that LPAL successfully reproduced the vascular tone changes that mimic CTEPH pathogenesis. In this model, the increased RVSP and RVH are likely related to enhanced SOCE and upregulated TRPC1 and TRPC6 expression levels in the distal PA. PMID- 26155751 TI - Exercise may be detrimental in hypertension: too much of a good thing! PMID- 26155754 TI - Linking Item Response Model Parameters. AB - With a few exceptions, the problem of linking item response model parameters from different item calibrations has been conceptualized as an instance of the problem of test equating scores on different test forms. This paper argues, however, that the use of item response models does not require any test score equating. Instead, it involves the necessity of parameter linking due to a fundamental problem inherent in the formal nature of these models-their general lack of identifiability. More specifically, item response model parameters need to be linked to adjust for the different effects of the identifiability restrictions used in separate item calibrations. Our main theorems characterize the formal nature of these linking functions for monotone, continuous response models, derive their specific shapes for different parameterizations of the 3PL model, and show how to identify them from the parameter values of the common items or persons in different linking designs. PMID- 26155755 TI - Identifiability of Diagnostic Classification Models. AB - Diagnostic classification models (DCMs) are important statistical tools in cognitive diagnosis. In this paper, we consider the issue of their identifiability. In particular, we focus on one basic and popular model, the DINA model. We propose sufficient and necessary conditions under which the model parameters are identifiable from the data. The consequences, in terms of the consistency of parameter estimates, of fulfilling or failing to fulfill these conditions are illustrated via simulation. The results can be easily extended to the DINO model through the duality of the DINA and DINO models. Moreover, the proposed theoretical framework could be applied to study the identifiability issue of other DCMs. PMID- 26155752 TI - Blockade of glucocorticoid receptors with RU486 attenuates cardiac damage and adipose tissue inflammation in a rat model of metabolic syndrome. AB - Glucocorticoids are stress hormones that modulate metabolic, inflammatory and cardiovascular processes. We recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive (DS) and Zucker rats, as a new animal model of metabolic syndrome (MetS). We have now investigated the effects of glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology and gene expression, as well as on glucose metabolism in this model. DS/obese rats were treated with the GR blocker RU486 (2 mg kg(-1) per day, subcutaneous) for 4 weeks beginning at 9 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean) littermates of DS/obese rats served as controls. Treatment of DS/obese rats with RU486 attenuated left ventricular (LV) fibrosis and diastolic dysfunction, as well as cardiac oxidative stress and inflammation, without affecting hypertension or LV hypertrophy. Administration of RU486 to DS/obese rats also inhibited the upregulation of GR and 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression at the mRNA and protein levels in the heart; it attenuated adiposity and adipose tissue inflammation, as well as the upregulation of GR and 11beta-HSD1 mRNA and protein expression in adipose tissue; it ameliorated fasting hyperinsulinemia as well as insulin resistance and glucose intolerance. Our results thus implicate the glucocorticoid-GR axis in the pathophysiology of MetS, and they suggest that GR blockade has therapeutic potential for the treatment of this condition. PMID- 26155753 TI - The luteotrophic function of galectin-1 by binding to the glycans on vascular endothelial growth factor receptor-2 in bovine luteal cells. AB - The corpus luteum (CL) is a temporary endocrine gland producing a large amount of progesterone, which is essential for the establishment and maintenance of pregnancy. Galectin-1 is a beta-galactose-binding protein that can modify functions of membrane glycoproteins and is expressed in the CL of mice and women. However, the physiological role of galectin-1 in the CL is unclear. In the present study, we investigated the expression and localization of galectin-1 in the bovine CL and the effect of galectin-1 on cultured luteal steroidogenic cells (LSCs) with special reference to its binding to the glycans on vascular endothelial growth factor receptor-2 (VEGFR-2). Galectin-1 protein was highly expressed at the mid and late luteal stages in the membrane fraction of bovine CL tissue and was localized to the surface of LSCs in a carbohydrate-dependent manner. Galectin-1 increased the viability in cultured LSCs. However, the viability of LSCs was decreased by addition of beta-lactose, a competitive carbohydrate inhibitor of galectin-1 binding activity. VEGFR-2 protein, like galectin-1, is also highly expressed in the mid CL, and it was modified by multi antennary glycans, which can be recognized by galectin-1. An overlay assay using biotinylated galectin-1 revealed that galectin-1 directly binds to asparagine linked glycans (N-glycans) on VEGFR-2. Enhancement of LSC viability by galectin-1 was suppressed by a selective inhibitor of VEGFR-2. The overall findings suggest that galectin-1 plays a role as a survival factor in the bovine CL, possibly by binding to N-glycans on VEGFR-2. PMID- 26155756 TI - Sample Size Determination Within the Scope of Conditional Maximum Likelihood Estimation with Special Focus on Testing the Rasch Model. AB - This paper refers to the exponential family of probability distributions and the conditional maximum likelihood (CML) theory. It is concerned with the determination of the sample size for three groups of tests of linear hypotheses, known as the fundamental trinity of Wald, score, and likelihood ratio tests. The main practical purpose refers to the special case of tests of the class of Rasch models. The theoretical background is discussed and the formal framework for sample size calculations is provided, given a predetermined deviation from the model to be tested and the probabilities of the errors of the first and second kinds. PMID- 26155757 TI - Modeling and Testing Differential Item Functioning in Unidimensional Binary Item Response Models with a Single Continuous Covariate: A Functional Data Analysis Approach. AB - Differential item functioning (DIF), referring to between-group variation in item characteristics above and beyond the group-level disparity in the latent variable of interest, has long been regarded as an important item-level diagnostic. The presence of DIF impairs the fit of the single-group item response model being used, and calls for either model modification or item deletion in practice, depending on the mode of analysis. Methods for testing DIF with continuous covariates, rather than categorical grouping variables, have been developed; however, they are restrictive in parametric forms, and thus are not sufficiently flexible to describe complex interaction among latent variables and covariates. In the current study, we formulate the probability of endorsing each test item as a general bivariate function of a unidimensional latent trait and a single covariate, which is then approximated by a two-dimensional smoothing spline. The accuracy and precision of the proposed procedure is evaluated via Monte Carlo simulations. If anchor items are available, we proposed an extended model that simultaneously estimates item characteristic functions (ICFs) for anchor items, ICFs conditional on the covariate for non-anchor items, and the latent variable density conditional on the covariate-all using regression splines. A permutation DIF test is developed, and its performance is compared to the conventional parametric approach in a simulation study. We also illustrate the proposed semiparametric DIF testing procedure with an empirical example. PMID- 26155758 TI - Industry Speed Bumps on Local Tobacco Control in Japan? The Case of Hyogo. AB - BACKGROUND: Despite being a signatory since 2004, Japan has not yet fully implemented Article 8 of the World Health Organization's Framework Convention on Tobacco Control regarding 100% protection against exposure to second-hand smoke (SHS). The Japanese government still recognizes designated smoking rooms (DSRs) in public space as a valid control measure. Furthermore, subnational initiatives for tobacco control in Japan are of limited effectiveness. Through an analysis of the Hyogo initiative in 2012, we identified key barriers to the achievement of a smoke-free environment. METHODS: Using a descriptive case-study approach, we analyzed the smoke-free policy development process. The information was obtained from meeting minutes and other gray literature, such as public records, well as key informant interviews. RESULTS: Hyogo Prefecture established a committee to propose measures against SHS, and most committee members agreed with establishing completely smoke-free environments. However, the hospitality sector representatives opposed regulation, and tobacco companies were allowed to make a presentation to the committee. Further, political power shifted against completely smoke-free environments in the context of upcoming local elections, which was an obvious barrier to effective regulation. Throughout the approving process, advocacy by civil society for stronger regulation was weak. Eventually, the ordinance approved by the Prefectural Assembly was even weaker than the committee proposal and included wide exemptions. CONCLUSIONS: The analysis of Hyogo's SHS control initiative shed light on three factors that present challenges to implementing tobacco control regulations in Japan, from which other countries can also draw lessons: incomplete national legislation, the weakness of advocacy by the civil society, and the interference of the tobacco industry. PMID- 26155759 TI - Pyogenic Liver Abscess and Risk of Acute Pancreatitis. PMID- 26155760 TI - Authors' Reply to 'Pyogenic Liver Abscess and Risk of Acute Pancreatitis'. PMID- 26155762 TI - Transplantation and Stem Cell Therapy for Cerebellar Degenerations. AB - Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration. PMID- 26155761 TI - Emotion and Theory of Mind in Schizophrenia-Investigating the Role of the Cerebellum. AB - Social cognitive dysfunction, including deficits in facial emotion recognition and theory of mind, is a core feature of schizophrenia and more strongly predicts functional outcome than neurocognition alone. Although traditionally considered to play an important role in motor coordination, the cerebellum has been suggested to play a role in emotion processing and theory of mind, and also shows structural and functional abnormalities in schizophrenia. The aim of this systematic review was to investigate the specific role of the cerebellum in emotion and theory of mind deficits in schizophrenia using previously published functional neuroimaging studies. PubMed and PsycINFO were used to search for all functional neuroimaging studies reporting altered cerebellum activity in schizophrenia patients during emotion processing or theory of mind tasks, published until December 2014. Overall, 14 functional neuroimaging studies were retrieved. Most emotion studies reported lower cerebellum activity in schizophrenia patients relative to healthy controls. In contrast, the theory of mind studies reported mixed findings. Altered activity was observed across several posterior cerebellar regions involved in emotion and cognition. Weaker cerebellum activity in schizophrenia patients relative to healthy controls during emotion processing may contribute to blunted affect and reduced ability to recognise emotion in others. This research could be expanded by examining the relationship between cerebellum function, symptomatology and behaviour, and examining cerebellum functional connectivity in patients during emotion and theory of mind tasks. PMID- 26155763 TI - The Adult Repetitive Behaviours Questionnaire-2 (RBQ-2A): A Self-Report Measure of Restricted and Repetitive Behaviours. AB - In two studies we developed and tested a new self-report measure of restricted and repetitive behaviours (RRB) suitable for adults. In Study 1, The Repetitive Behaviours Questionnaire-2 for adults (RBQ-2A) was completed by a sample of 163 neurotypical adults. Principal components analysis revealed two components: Repetitive Motor Behaviours and Insistence on Sameness. In Study 2, the mean RBQ 2A scores of a group of adults with autism spectrum disorder (ASD; N = 29) were compared to an adult neurotypical group (N = 37). The ASD sample had significantly higher total and subscale scores. These results indicate that the RBQ-2A has utility as a self-report questionnaire measure of RRBs suitable for adults, with potential clinical application. PMID- 26155764 TI - Psychiatric Symptoms in Youth with a History of Autism and Optimal Outcome. AB - Since autism spectrum disorder (ASD) is often comorbid with psychiatric disorders, children who no longer meet criteria for ASD (optimal outcome; OO) may still be at risk for psychiatric disorders. A parent interview for DSM-IV psychiatric disorders (K-SADS-PL) for 33 OO, 42 high-functioning autism (HFA) and 34 typically developing (TD) youth, ages 8-21, showed that OO and HFA groups had elevated current ADHD and specific phobias, with tics in HFA. In the past, the HFA group also had elevated depression and ODD, and the OO group had tics. The HFA group also showed subthreshold symptoms of specific and social phobias, and generalized anxiety. Psychopathology in the OO group abated over time as did their autism, and decreased more than in HFA. PMID- 26155765 TI - Can pregabalin prevent paclitaxel-associated neuropathy?--An ACCRU pilot trial. AB - PURPOSE: Paclitaxel can cause an acute pain syndrome (P-APS), considered to be an acute form of neuropathy and chronic chemotherapy-induced peripheral neuropathy (CIPN). Anecdotal reports suggested that gabapentin may be helpful in the prevention of these toxicities. The purpose of this pilot study was to obtain data to support or refute the utility of pregabalin for the prevention of P-APS and CIPN. METHODS: Patients scheduled to receive weekly paclitaxel (80 mg/m(2)/dose) were randomized 1:1 to receive pregabalin 75 mg or a placebo, twice daily, during the 12 weeks of chemotherapy. Patients completed the European Organization of Research and Treatment of Cancer Quality of Life (EORTC QLQ) CIPN20 questionnaire at baseline, prior to each dose of paclitaxel and monthly for 6 months post-treatment. Patients completed a post-paclitaxel questionnaire for 6 days after each dose of paclitaxel and an acute pain syndrome symptom questionnaire on day 8. The primary end point was to determine the effect of pregabalin on the maximum of the worst acute pain scores for the week following paclitaxel administration for cycle 1. RESULTS: Forty-six patients were randomly assigned to the treatment or placebo arm. There was no suggestion of a difference between the two study arms with regard to P-APS measures. While there was a suggestion that pregabalin decreased numbness, there was no suggestion that it decreased tingling, pain, or the EORTC QLQ-CIPN20 subscale scores. There were no evident toxicity differences between the two study arms. CONCLUSIONS: The results of this pilot trial do not support that pregabalin is helpful for preventing P APS or paclitaxel-associated CIPN. PMID- 26155766 TI - Large-scale Direct Targeting for Drug Repositioning and Discovery. AB - A system-level identification of drug-target direct interactions is vital to drug repositioning and discovery. However, the biological means on a large scale remains challenging and expensive even nowadays. The available computational models mainly focus on predicting indirect interactions or direct interactions on a small scale. To address these problems, in this work, a novel algorithm termed weighted ensemble similarity (WES) has been developed to identify drug direct targets based on a large-scale of 98,327 drug-target relationships. WES includes: (1) identifying the key ligand structural features that are highly-related to the pharmacological properties in a framework of ensemble; (2) determining a drug's affiliation of a target by evaluation of the overall similarity (ensemble) rather than a single ligand judgment; and (3) integrating the standardized ensemble similarities (Z score) by Bayesian network and multi-variate kernel approach to make predictions. All these lead WES to predict drug direct targets with external and experimental test accuracies of 70% and 71%, respectively. This shows that the WES method provides a potential in silico model for drug repositioning and discovery. PMID- 26155767 TI - Reversible nanostructuration of microfluidic electrode devices by CNT magnetic co entrapment. AB - Carbon nanotubes (CNTs) have been extensively used to produce electrodes of enhanced performance but have only been very recently exploited in microfluidic devices. In these cases, CNT electrodes had to be produced prior to device assembly, which might damage the CNT layer. Here, we show a fast and simple method for the reversible nanostructuration of microfluidic electrode devices in situ. The procedure is based on the attachment of single-walled CNTs (SWCNTs) onto the surface of magnetic particles (MPs) and magnetic confinement of the MP/SWCNT composite onto the sensor in a two-step process that provided homogeneous coating. As it is shown, subsequent magnet removal allows MP/SWCNT release and electrode reutilization. Compared to most previously described methods, ours is faster, simpler and also reversible. PMID- 26155768 TI - Erratum to: The Minimum Clinically Important Difference of the Patient-rated Wrist Evaluation Score for Patients With Distal Radius Fractures. PMID- 26155770 TI - Editor's Spotlight/Take 5: Adipose-derived Mesenchymal Stem Cells Are Phenotypically Superior for Regeneration in the Setting of Osteonecrosis of the Femoral Head. PMID- 26155769 TI - 2015 Marshall Urist Young Investigator Award: Prognostication in Patients With Long Bone Metastases: Does a Boosting Algorithm Improve Survival Estimates? AB - BACKGROUND: Survival estimation guides surgical decision-making in metastatic bone disease. Traditionally, classic scoring systems, such as the Bauer score, provide survival estimates based on a summary score of prognostic factors. Identification of new factors might improve the accuracy of these models. Additionally, the use of different algorithms--nomograms or boosting algorithms- could further improve accuracy of prognostication relative to classic scoring systems. A nomogram is an extension of a classic scoring system and generates a more-individualized survival probability based on a patient's set of characteristics using a figure. Boosting is a method that automatically trains to classify outcomes by applying classifiers (variables) in a sequential way and subsequently combines them. A boosting algorithm provides survival probabilities based on every possible combination of variables. QUESTIONS/PURPOSES: We wished to (1) assess factors independently associated with decreased survival in patients with metastatic long bone fractures and (2) compare the accuracy of a classic scoring system, nomogram, and boosting algorithms in predicting 30-, 90-, and 365-day survival. METHODS: We included all 927 patients in our retrospective study who underwent surgery for a metastatic long bone fracture at two institutions between January 1999 and December 2013. We included only the first procedure if patients underwent multiple surgical procedures or had more than one fracture. Median followup was 8 months (interquartile range, 3-25 months); 369 of 412 (90%) patients who where alive at 1 year were still in followup. Multivariable Cox regression analysis was used to identify clinical and laboratory factors independently associated with decreased survival. We created a classic scoring system, nomogram, and boosting algorithms based on identified variables. Accuracy of the algorithms was assessed using area under the curve analysis through fivefold cross validation. RESULTS: The following factors were associated with a decreased likelihood of survival after surgical treatment of a metastatic long bone fracture, after controlling for relevant confounding variables: older age (hazard ratio [HR], 1.0; 95% CI, 1.0-1.0; p < 0.001), additional comorbidity (HR, 1.2; 95% CI, 1.0-1.4; p = 0.034), BMI less than 18.5 kg/m(2) (HR, 2.0; 95% CI, 1.2-3.5; p = 0.011), tumor type with poor prognosis (HR, 1.8; 95% CI, 1.6-2.2; p < 0.001), multiple bone metastases (HR, 1.3; 95% CI, 1.1-1.6; p = 0.008), visceral metastases (HR, 1.6; 95% CI, 1.4-1.9; p < 0.001), and lower hemoglobin level (HR, 0.91; 95% CI, 0.87-0.96; p < 0.001). The survival estimates by the nomogram were moderately accurate for predicting 30-day (area under the curve [AUC], 0.72), 90-day (AUC, 0.75), and 365-day (AUC, 0.73) survival and remained stable after correcting for optimism through fivefold cross validation. Boosting algorithms were better predictors of survival on the training datasets, but decreased to a performance level comparable to the nomogram when applied on testing datasets for 30-day (AUC, 0.69), 90-day (AUC, 0.75), and 365-day (AUC, 0.72) survival prediction. Performance of the classic scoring system was lowest for all prediction periods. CONCLUSIONS: Comorbidity status and BMI are newly identified factors associated with decreased survival and should be taken into account when estimating survival. Performance of the boosting algorithms and nomogram were comparable on the testing datasets. However, the nomogram is easier to apply and therefore more useful to aid surgical decision making in clinical practice. LEVEL OF EVIDENCE: Level III, prognostic study. PMID- 26155771 TI - Paenibacillus herberti sp. nov., an endophyte isolated from Herbertus sendtneri. AB - Strain R33(T), an endophyte recovered from Herbertus sendtneri, was identified as representing a novel species of the genus Paenibacillus by using a polyphasic taxonomic approach. The novel strain was observed to be a Gram-stain positive, aerobic, rod-shaped, motile and endospore-forming bacterium. The major polar lipids of strain R33(T) were identified as diphosphatidylglycerol, phosphatidylethanolamine, along with lesser amounts of phosphatidylglycerol, three unidentified aminophospholipids, two unidentified phospholipids and two unidentified lipids. The predominant isoprenoid quinone was identified as MK-7. The major fatty acids (>8.0 %) were found to be anteiso-C15:0 (40.0 %), C16:1 omega11c (9.4 %), C16:1 omega7c alcohol (8.5 %) and C16:0 (8.2 %). The diamino acid found in the cell-wall peptidoglycan was meso-diaminopimelic acid. The G+C content of genomic DNA was determined to be 56.9 mol%. The 16S rRNA gene sequence similarities of strain R33(T) to other Paenibacillus species ranged from 91.6 to 97.2 %, with high similarities to Paenibacillus humicus PC-147(T) and Paenibacillus pasadenensis SAFN-007(T). The phylogenetic analyses based on 16S rRNA gene sequences and the partial rpoB gene confirmed that strain R33(T) belongs to the genus Paenibacillus. However, strain R33(T) shows differential molecular characteristics compared to other related Paenibacillus species based on 16S rDNA-RFLP analyses; the DNA-DNA relatedness values between strain R33(T) and P. humicus PC-147(T), and that between strain R33(T) and P. pasadenensis SAFN 007(T), were 35.0 +/- 2.0 and 41.4 +/- 0.9 %, respectively. Based on its phenotypic, chemotaxonomic and phylogenetic properties, strain R33(T) is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus herberti is proposed (type strain R33(T) = CGMCC 1.15042(T) = DSM 29849(T)). PMID- 26155772 TI - Sphingomonas panacis sp. nov., isolated from rhizosphere of rusty ginseng. AB - The type strain DCY99(T) was isolated from soil collected from a ginseng field in Hwacheon, Republic of Korea. Strain DCY99(T) is Gram-negative, non-spore forming, motile, rod-shaped, and strictly aerobic. The bacteria grow optimally at 25-30 degrees C and pH 6.0-6.5. Phylogenetically, strain DCY99(T) is most closely related to Sphingomonas oligophenolica JCM 12082(T), followed by Sphingomonas asaccharolytica KCTC 2825(T), Sphingomonas mali KCTC 2826(T), Sphingomonas cynarae JCM17498(T), Sphingomonas pruni KCTC 2824(T), and Sphingomonas glacialis DSM 22294(T). The DNA-DNA relatedness between strain DCY99(T) and S. oligophenolica JCM 12082(T) was 15.6 +/- 0.4 %, and the DNA G+C content of strain DCY99(T) was 64.4 mol%. An isoprenoid quinone was detected and identified as ubiquinone Q-10, and sym-homospermidine was identified as the major polyamine of DCY99(T). The major polar lipids were identified as sphingoglycolipid, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylcholine. C14:02OH, C16:0, and summed feature 8 (C18:1 omega7c:/C18:1 omega6c) were identified as the major fatty acids present in DCY99(T). The results of physiological and biochemical tests allowed strain DCY99(T) to be differentiated phenotypically from other recognized species belonging to the genus Sphingomonas. Therefore, it is suggested that the newly isolated organism represents a novel species, for which the name Sphingomonas panacis sp. nov. is proposed with the type strain designated as DCY99(T) (=JCM 30806(T) =KCTC 42347(T)). PMID- 26155773 TI - Nitrospirillum irinus sp. nov., a diazotrophic bacterium isolated from the rhizosphere soil of Iris and emended description of the genus Nitrospirillum. AB - A polyphasic approach was used to characterize a novel nitrogen-fixing bacterial strain, designated YC6995(T), isolated from the rhizosphere soil of Iris ensata var. spontanea (Makino) Nakai inhabiting a wetland located at an altitude of 960 m on Jiri Mountain, Korea. Strain YC6995(T) cells were Gram-negative, and rod shaped, with motility provided by a single polar flagellum. Optimal growth conditions were 30 degrees C and pH 7.0. The major fatty acids of strain YC6995(T) were C18:1 omega7c, C18:1 2-OH and C16:0 3-OH. The major respiratory quinone was ubiquinone-10 (Q-10). The polar lipids were phosphatidylethanolamine, phosphatidyldimethylethanolamine, phosphatidylcholine, phosphatidylglycerol and unidentified glycolipids. The genomic DNA G+C content was 64.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed strain YC6995(T) to form a phyletic lineage with Nitrospirillum amazonense DSM 2787(T) with a high sequence similarity (97.2 %), but it displayed low sequence similarity with other remotely related genera, including Azospirillum (<93 %), Rhodocista (93.1-93.4 %), and Skermanella (91.2-93.3 %) in the family Alphaproteobacteria. Based on the phenotypic, chemotaxonomic, and phylogenetic evidences, strain YC6995(T) represents a novel species within the genus Nitrospirillum, for which the name Nitrospirillum irinus sp. nov. is proposed. The type strain is YC6995(T) (= KACC 13777(T) = DSM 22198(T)). An emended description of the genus Nitrospirillum is also proposed. PMID- 26155774 TI - Random regression models to account for the effect of genotype by environment interaction due to heat stress on the milk yield of Holstein cows under tropical conditions. AB - The present study had the following objectives: to compare random regression models (RRM) considering the time-dependent (days in milk, DIM) and/or temperature * humidity-dependent (THI) covariate for genetic evaluation; to identify the effect of genotype by environment interaction (G*E) due to heat stress on milk yield; and to quantify the loss of milk yield due to heat stress across lactation of cows under tropical conditions. A total of 937,771 test-day records from 3603 first lactations of Brazilian Holstein cows obtained between 2007 and 2013 were analyzed. An important reduction in milk yield due to heat stress was observed for THI values above 66 (-0.23 kg/day/THI). Three phases of milk yield loss were identified during lactation, the most damaging one at the end of lactation (-0.27 kg/day/THI). Using the most complex RRM, the additive genetic variance could be altered simultaneously as a function of both DIM and THI values. This model could be recommended for the genetic evaluation taking into account the effect of G*E. The response to selection in the comfort zone (THI <= 66) is expected to be higher than that obtained in the heat stress zone (THI > 66) of the animals. The genetic correlations between milk yield in the comfort and heat stress zones were less than unity at opposite extremes of the environmental gradient. Thus, the best animals for milk yield in the comfort zone are not necessarily the best in the zone of heat stress and, therefore, G*E due to heat stress should not be neglected in the genetic evaluation. PMID- 26155775 TI - Pericardial covered stent for coronary perforations. AB - OBJECTIVES: To evaluate initial and long term results of coronary perforation treatment with pericardial covered stent. BACKGROUND: Iatrogenic coronary perforation is a rare life threatening complication of percutaneous coronary interventions (PCI) occurring in 0.1-0.8% of cases. Covered stents are the mainstay of therapy for coronary perforation. However, polytetrafluoroethylene covered stents are bulky with limited flexibility and thus may not be easy to deliver in difficult anatomy. Therefore, they are reserved to perforations in proximal or mid straight segments where their delivery is relatively easy. The pericardial covered stent is a highly deliverable fully covered stent that may be used to treat coronary perforations. Only a single case has been reported of the use of this stent in its previous version for the treatment of coronary perforation. METHODS: The electronic databases of four tertiary medical centers were retrospectively reviewed for cases of coronary perforations in which PCS was used. During a five years period, between 2008 and 2013, 18,364 patients underwent PCI in these centers. Nine cases of perforations for which balloon dilatation was not sufficient and pericardial covered stent was used were recorded. RESULTS: All nine cases were successfully treated with pericardial covered stent. Six of the patients underwent repeated angiography at 2-15 months, and in two of them instent restenosis that warranted repeated angioplasty was observed. One of them was catheterized for NSTEMI 3 months after the covered stent implantation, and stent thrombosis was demonstrated. CONCLUSIONS: Pericardial covered stents offer a safe and effective therapy for coronary perforation when balloon inflation and reversal of anticoagulation are insufficient. PMID- 26155776 TI - Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant. AB - The Endothelial Protein C receptor (EPCR) is essential for the anticoagulant and cytoprotective functions of the Protein C (PC) system. Selected variants of the malaria parasite protein, Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) associated with severe malaria, including cerebral malaria, specifically target EPCR on vascular endothelial cells. Here, we examine the cellular response to PfEMP1 engagement to elucidate its role in malaria pathogenesis. Binding of the CIDRalpha1.1 domain of PfEMP1 to EPCR obstructed activated PC (APC) binding to EPCR and induced a loss of cellular EPCR functions. CIDRalpha1.1 severely impaired endothelial PC activation and effectively blocked APC-mediated activation of protease-activated receptor-1 (PAR1) and associated barrier protective effects of APC on endothelial cells. A soluble EPCR variant (E86A sEPCR) bound CIDRalpha1.1 with high affinity and did not interfere with (A)PC binding to cellular EPCR. E86A-sEPCR used as a decoy to capture PfEMP1, permitted normal PC activation on endothelial cells, normal barrier protective effects of APC, and greatly reduced cytoadhesion of infected erythrocytes to brain endothelial cells. These data imply important contributions of PfEMP1-induced protein C pathway defects in the pathogenesis of severe malaria. Furthermore, the E86A-sEPCR decoy provides a proof-of-principle strategy for the development of novel adjunct therapies for severe malaria. PMID- 26155777 TI - Compound eye formation in the termite Incisitermes minor (Isoptera: Kalotermitidae). AB - The postembryonic development and caste differentiation patterns of lower termites have been described multiple times in a variety of different species. However, most of these studies focused on gross ontogeny, without carefully describing the maturation of any particular organ or organ system. The few studies that have attempted to correlate caste development and organ differentiation have produced somewhat inconsistent results, especially in the area of eye formation. Therefore, in order to help further elucidate the relationship between eye formation and postembryonic differentiation in lower termites, we studied eye development in the termite, Incisitermes minor (Hagen). Eye formation in I. minor began in the earliest larvae, with only an eye primordium. However, in all later larval stages, characteristic eye structures were observed and were shown to progressively differentiate through larval and nymphal stages. Curiously, pigmentation began with three to eight groups of cells in early larvae and the number of these pigmented groups increased along the developmental time course. Ultimately, a uniformly pigmented eye area was formed by the early nymphal stage. The overall eye area also gradually increased along with normal caste development, but the characteristic lenses seen in a prototypical insect compound eye did not completely form until after the final nymphal stage. Electrophysiological measurements provided clear evidence that eyes were indeed functional at all stages of development where pigment was present. Based upon this data, the eye development pattern in I. minor appeared to follow a divergent pathway from holometabolous insects and an intermediate pathway between typical hemimetabolous eye development and the heterochronic shift observed in other termite species. PMID- 26155778 TI - Different Heavy Metal Accumulation Strategies of Epilithic Lichens Colonising Artificial Post-Smelting Wastes. AB - Lichens appear to be essential and effective colonisers of bare substrates including the extremely contaminated wastes of slag dumps. This study examines the metal accumulation capacity of epilithic lichens growing directly on the surface of artificial slag sinters. Four species representing different growth forms, i.e., crustose Candelariella aurella, Lecanora muralis, and Lecidea fuscoatra and fruticose Stereocaulon nanodes, were selected to evaluate the relationships between zinc, lead, cadmium, and nickel contents in their thalli and host substrates. Bioaccumulation factors of examined crustose lichens showed their propensity to hyperaccumulate heavy metals. Contrarily, concentrations of metals in fruticose thalli of S. nanodes were, as a rule, lower than in the corresponding substrates. This indicates that the growth form of thalli and degree of thallus adhesion to the substrate has a significant impact on metal concentrations in lichens colonising post-smelting wastes. Nonlinear regression models described by power functions show that at greater levels of Pb concentration in the substrate, the ability of C. aurella, L. muralis and L. fuscoatra to accumulate the metal experiences a relative decrease, whereas hyperbolic function describes a similar trend in relation to Ni content in S. nanodes. This phenomenon may be an important attribute of lichens that facilitates their colonisation of the surface of slag wastes. PMID- 26155779 TI - Adherence to WCRF/AICR lifestyle recommendations for cancer prevention and the risk of Barrett's esophagus onset and evolution to esophageal adenocarcinoma: results from a pilot study in a high-risk population. AB - PURPOSE: While adherence to the World Cancer Research Fund (WCRF) guidelines on lifestyle and cancer was recently proven to be associated with an increased risk of esophageal cancer, no investigation has yet been carried out on its role on Barrett's esophagus (BE) development and its progression to esophageal adenocarcinoma (EAC). The primary aim of this study was to evaluate the role of adherence to WCRF lifestyle recommendations in BE onset and progression. The secondary aim was to investigate the association between disease progression and specific aspects of diet and lifestyle. METHODS: Established risk factors for BE and EAC development and adherence to WCRF guidelines were assessed in 107 consecutive patients undergoing an upper gastrointestinal endoscopy for symptoms suggesting gastroesophageal reflux (GERD) and a suspected diagnosis of BE/dysplasia on BE. Patients were divided according to histology: those with GERD without metaplasia, with non-dysplastic BE, with low-grade dysplasia, with high grade dysplasia or with early EAC. The four groups were expressed as an ordered categorical variable of disease progression. An ordered logit model was estimated to identify the independent predictors of disease progression. RESULTS: Adherence to WCRF guidelines was identified as independent protective factor (OR 0.51, 95 % CI 0.37-0.67) of disease progression. Disease progression was associated with reduced adherence to guidelines on physical activity (from 48.2 to 5.3 %, p = 0.001), sedentary habits (from 33.3 to 0 %, p = 0.03), fruit consumption (from 37.0 to 5.6 %, p = 0.02) and processed meat consumption (from 51.9 to 10.5 %, p = 0.002). CONCLUSION: Adherence to WCRF guidelines has a protective factor in BE onset and its evolution to EAC. PMID- 26155781 TI - "Edgeboost": A Novel Technique to Extend the Ablation Zone Lateral to a Two-Probe Bipolar Radiofrequency Device. AB - BACKGROUND: The dual-electrode bipolar-RFA (B-RFA) is increasingly used to ablate large liver tumours (3-7 cm). However, the challenging aspect of B-RFA is the placement of the two electrodes around the tumour. Realignment often requires the electrodes to be extracted and reinserted. AIM: The aim of this study is to examine "Edgeboost", a novel technique to increase the lateral ablation dimension without requiring any realignment of the electrodes. METHODS AND MATERIALS: An egg-white model and an ex vivo calf liver model were used compare the standard bipolar mode ablation to Edgeboost-1 (reaching full impedance in bipolar mode initially, then cycling in unipolar mode between left and right probes) and Edgeboost-2 (similar to Edgeboost-1 but not reaching full impedance initially in bipolar mode in order to minimize charring and, thus, to increase total ablation time). RESULTS: A significantly larger outer lateral ablation dimension to the probe was achieved with Edgeboost-1 compared to the standard method in the liver model (1.14 cm, SD: 0.16 vs. 0.44 cm, SD: 0.24, p = 0.04). Edgeboost-2 achieved the largest outer lateral ablation dimension of 1.75 cm (SD: 0.35). A similar association was seen in the egg model. Edgeboost-2 almost doubled the mass ablated with standard bipolar alone (mass ratio: 1:1.94 in egg white and 1:1.84 in liver). CONCLUSION: This study demonstrates that the novel "Edgeboost" technique can increase the outer lateral ablation dimension without requiring the two inserted electrodes to be reinserted. This would be beneficial for interventionists who use the dual B-RFA. PMID- 26155780 TI - Pomegranate inhibits neuroinflammation and amyloidogenesis in IL-1beta-stimulated SK-N-SH cells. AB - PURPOSE: Pomegranate fruit, Punica granatum L. (Punicaceae), and its constituents have been shown to inhibit inflammation. In this study, we aimed to assess the effects of freeze-dried pomegranate (PWE) on PGE2 production in IL-1beta stimulated SK-N-SH cells. METHODS: An enzyme immunoassay (EIA) was used to measure prostaglandin E2 (PGE2) production from supernatants of IL-1beta stimulated SK-N-SH cells. Expression of COX-2, phospho-IkappaB, and phospho-IKK proteins was evaluated, while NF-kappaB reporter gene assay was carried out in TNFalpha-stimulated HEK293 cells to determine the effect of PWE on NF-kappaB transactivation. Levels of BACE-1 and Abeta in SK-N-SH cells stimulated with IL 1beta were measured with an in cell ELISA. RESULTS: PWE (25-200 MUg/ml) dose dependently reduced COX-2-dependent PGE2 production in SK-N-SH cells stimulated with IL-1beta. Phosphorylation of IkappaB and IKK was significantly (p < 0.001) inhibited by PWE (50-200 MUg/ml). Our studies also show that PWE (50-200 MUg/ml) significantly (p < 0.01) inhibited NF-kappaB transactivation in TNFalpha stimulated HEK293 cells. Furthermore, PWE inhibited BACE-1 and Abeta expression in SK-N-SH cells treated with IL-1beta. CONCLUSIONS: Taken together, our study demonstrates that pomegranate inhibits inflammation, as well as amyloidogenesis in IL-1beta-stimulated SK-N-SH cells. We propose that pomegranate is a potential nutritional strategy in slowing the progression of neurodegenerative disorders such as Alzheimer's disease. PMID- 26155782 TI - Wedge hybrid plasmonic THz waveguide with long propagation length and ultra-small deep-subwavelength mode area. AB - We present a novel design of wedge hybrid plasmonic terahertz (THz) waveguide consisting of a silicon (Si) nanowire cylinder above a triangular gold wedge with surrounded high-density polyethylene as cladding. It features long propagation length and ultra-small deep-subwavelength mode confinement. The mode properties of wedge hybrid plasmonic THz waveguide are comprehensively characterized in terms of propagation length (L), normalized mode area (Aeff/A0), figure of merit (FoM), and chromatic dispersion (D). The designed wedge hybrid plasmonic THz waveguide enables an ultra-small deep-subwavelength mode area which is more than one-order of magnitude smaller compared to previous rectangular one. When choosing the diameter of Si nanowire cylinder, a smaller diameter (e.g. 10 MUm) is preferred to achieve longer L and higher FoM, while a larger diameter (e.g. 60 MUm) is favorable to obtain smaller Aeff/A0 and higher FoM. We further study the impacts of possible practical fabrication errors on the mode properties. The simulated results of propagation length and normalized mode area show that the proposed wedge hybrid plasmonic THz waveguide is tolerant to practical fabrication errors in geometry parameters such as misalignment in the horizontal direction, variation of wedge tip angle, and variation of wedge tip curvature radius. PMID- 26155783 TI - Clinical findings in relation to mortality in non-tuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria. AB - We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p < 0.001) and had less fatal underlying diseases (23 % vs. 47 %, p = 0.001) as compared to other NTM patients. Symptoms compatible with NTM infection had lasted for less than a year in 34 % of MAC patients but in 54 % of other NTM patients (p = 0.037). Pulmonary MAC patients had a significantly lower risk of death compared to pulmonary other NTM (hazard ratio [HR] 0.50, 95 % confidence interval [CI] 0.33-0.77, p = 0.002) or subgroup of other slowly growing NTM (HR 0.55, 95 % CI 0.31-0.99, p = 0.048) or as rapidly growing NTM (HR 0.47, 95 % CI 0.25-0.87, p = 0.02). The median survival time was 13.0 years (95 % CI 5.9-20.1) for pulmonary MAC but 4.6 years (95 % CI 3.4-5.9) for pulmonary other NTM. Serious underlying diseases (HR 3.21, 95 % CI 2.05-5.01, p < 0.001) and age (HR 1.07, 95 % CI 1.04-1.09, p < 0.001) were the significant predictors of mortality and female sex was a predictor of survival (HR 0.38, 95 % CI 0.24-0.59, p < 0.001) in the multivariate analysis. Pulmonary MAC patients had better prognosis than pulmonary other NTM patients. The symptom onset suggests a fairly rapid disease course. PMID- 26155784 TI - Impact of HIV infection on sustained virological response to treatment against hepatitis C virus with pegylated interferon plus ribavirin. AB - It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naive hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation. PMID- 26155787 TI - Rapid recurrence and bilateral lungs, multiple bone metastasis of malignant solitary fibrous tumor of the right occipital lobe: report of a case and review. AB - BACKGROUND: Intracranial malignant solitary fibrous tumor (MSFT) is extremely rare. The authors report a case of MSFT of the right occipital lobe with a rapid recurrence and bilateral lung, multiple bone metastasis. CASE PRESENTATION: The patient was a 25-year-old male presenting with headache, nausea and visual disturbances without obvious cause. Three times right-side occipital craniotomies were performed and two times postoperative conformal radiotherapy were administered within one year. 4 months after the third time of right-side occipital craniotomy, the patient felt right chest pain and neck pain. Positron emission tomography/computed tomography (PET/CT) showed tumor recurrence of the right occipital lobe and bilateral lung metastasis, multiple bone metastasis including: vertebrae, libs, the left iliac wing, sacrum, the right ischium and upper parts of both femurs. Ultrasound guided puncture biopsy of left-side back of the neck and CT guided puncture biopsy of the third lumbar vertebra were performed. General sample showed grayish white or grayish red with irregular shape. Histopathologically, the tumor was composed of areas of alternating hypercellularity and hypocellularity with spindle-shaped cells, which arranged as fascicular, storiform pattern or patternless pattern, with intervening irregular eosinophilic collagen bundles. Some areas showed hemangiopericytoma-like perivascular pattern and perivascular hyalinization. Tumor cells were pleomorphic with mitotic counts of more than 4 per 10 high power fields and showed coagulative necrosis. Immunohistochemically, tumor cells were diffusely positive for vimentin and CD99, focal positive for CD34, bcl-2 and Actin. Ki-67 labelling index was more than 40%. The final pathological diagnosis was MSFT of the right occipital lobe, metastatic MSFT of left-side back of the neck and the third lumbar vertebra. CONCLUSION: The MSFT of the right occipital lobe with recurrence and bilateral lung, multiple bone metastasis is extremely rare. Although intracranial MSFT is extremely rare, it should be considered in the differential diagnosis. Definite diagnosis depended mainly on pathological morphology and immunohistochemistry. The prognosis of MSFT is poor due to recurrence and metastasis. Complete resection of intracranial MSFT is difficult, and carful follow-up is needed. PMID- 26155788 TI - Rheumatoid arthritis-associated autoantibodies in non-rheumatoid arthritis patients with mucosal inflammation: a case-control study. AB - INTRODUCTION: Rheumatoid arthritis-associated autoantibodies (RA-AAB) can be present in serum years before clinical onset of rheumatoid arthritis (RA). It has been hypothesized that initiation of RA-AAB generation occurs at inflamed mucosal surfaces, such as in the oral cavity or lungs. The aim of this study was to assess systemic presence of RA-AAB in patients without RA who had oral or lung mucosal inflammation. METHODS: The presence of RA-AAB (immunoglobulin A [IgA] and IgG anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), IgM and IgA rheumatoid factor (RF), IgG anti-carbamylated protein antibodies and IgG and IgA anti-citrullinated peptide antibodies against fibrinogen, vimentin and enolase) were determined in sera of non-RA patients with periodontitis (PD, n = 114), bronchiectasis (BR, n = 80) or cystic fibrosis (CF, n = 41). Serum RA-AAB levels were compared with those of periodontally healthy controls (n = 36). Patients with established RA (n = 86) served as a reference group. Association of the diseases with RA-AAB seropositivity was assessed with a logistic regression model, adjusted for age, sex and smoking. RESULTS: Logistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant. IgA anti-CCP seropositivity was associated with CF and RA. IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant. IgA RF seropositivity was associated with CF and RA. Apart from an influence of smoking on IgA RF in patients with RA, there was no influence of age, sex or smoking on the association of RA-AAB seropositivity with the diseases. Anti-CarP levels were increased only in patients with RA. The same held for IgG reactivity against all investigated citrullinated peptides. CONCLUSION: Although overall levels were low, RA-AAB seropositivity was associated with lung mucosal inflammation (BR and CF) and may be associated with oral mucosal inflammation (PD). To further determine whether mucosal inflammation functions as a site for induction of RA AAB and precedes RA, longitudinal studies are necessary in which RA-AAB of specifically the IgA isotype should be assessed in inflamed mucosal tissues and/or in their inflammatory exudates. PMID- 26155789 TI - Genome-wide characterization of intergenic polyadenylation sites redefines gene spaces in Arabidopsis thaliana. AB - BACKGROUND: Messenger RNA polyadenylation is an essential step for the maturation of most eukaryotic mRNAs. Accurate determination of poly(A) sites helps define the 3'-ends of genes, which is important for genome annotation and gene function research. Genomic studies have revealed the presence of poly(A) sites in intergenic regions, which may be attributed to 3'-UTR extensions and novel transcript units. However, there is no systematically evaluation of intergenic poly(A) sites in plants. RESULTS: Approximately 16,000 intergenic poly(A) site clusters (IPAC) in Arabidopsis thaliana were discovered and evaluated at the whole genome level. Based on the distributions of distance from IPACs to nearby sense and antisense genes, these IPACs were classified into three categories. About 70 % of them were from previously unannotated 3'-UTR extensions to known genes, which would extend 6985 transcripts of TAIR10 genome annotation beyond their 3'-ends, with a mean extension of 134 nucleotides. 1317 IPACs were originated from novel intergenic transcripts, 37 of which were likely to be associated with protein coding transcripts. 2957 IPACs corresponded to antisense transcripts for genes on the reverse strand, which might affect 2265 protein coding genes and 39 non-protein-coding genes, including long non-coding RNA genes. The rest of IPACs could be originated from transcriptional read-through or gene mis-annotations. CONCLUSIONS: The identified IPACs corresponding to novel transcripts, 3'-UTR extensions, and antisense transcription should be incorporated into current Arabidopsis genome annotation. Comprehensive characterization of IPACs from this study provides insights of alternative polyadenylation and antisense transcription in plants. PMID- 26155790 TI - Discordance between physician-rated health and an objective health measure among institutionalized older people. AB - BACKGROUND: Although physician-rated health is emerging as a potentially useful variable in research, with implications in practice, it has not been analyzed. Moreover, one of its most important aspects, namely, concordance with patients' objective health state, has not been investigated. This study sought to measure concordance between physician-rated health and an objective health measure, and assess both measures' validity in predicting death. METHODS: The data for the study were drawn from a 1998-1999 survey and subsequent mortality follow-up of residential and nursing homes in Madrid (Spain). Study subjects were 630 residents aged >=65 years, and their respective facility physicians. Measures included agreement between physicians' rating of residents' overall health (good, intermediate or poor) and an objective measure of residents' health (good, intermediate or poor), based on functional capacity, cognitive status, and number of chronic conditions. Overrating was defined as any case where health, rated as good by a physician, was objectively rated as poor. RESULTS: Whereas 45% of physicians and 55% of residents rated their health as good, only 4% of such residents had good objective health. Of those who received a physician rating of good/very good health, 39.0% had poor objective health. There was evidence of clear overrating in 18% of the population, and clear to moderate overrating in 73% of the population. In terms of power to predict mortality, the pattern of behavior shown by the objective health measure was good, graded and congruent, and better than that shown by physician-rated health. CONCLUSION: Physician overrating of the overall health of older persons in residential and nursing homes, would appear to be very high. Although some degree of contextualization by physicians in this setting might be considered reasonable, the degree of overrating in our population seems nevertheless excessive. PMID- 26155791 TI - Simultaneous diagnosis of severe imported Plasmodium falciparum malaria and HIV: report of three cases. AB - The increasing number of travellers to and from areas where considerable overlap between high malaria transmission and elevated prevalence of human immunodeficiency virus (HIV) infection exists, augment the probability that returning travellers to non-endemic countries might present with both infections. The presence of such co-infection can increase the severity of malaria episodes and also can change the progression of HIV infection. This article describes three travellers returning from malaria-endemic areas that had simultaneous diagnosis of severe Plasmodium falciparum malaria and HIV infection. Despite the severe forms of malaria and HIV co-infection, all patients responded successfully to anti-malarial treatment. Malaria and HIV interact with one another, with HIV infection increasing parasite burden, clinical severity and risk of complications of malaria; malaria seems to create an immunological interaction favourable to HIV spread and replication, with impact in progression to AIDS. The presence of malaria and HIV co-infection also poses other challenges related to treatment response, level of care and possible interactions of drugs. The authors recommend that all patients with fever returning from malaria endemic areas should be screened both for malaria and HIV infection. PMID- 26155793 TI - Less invasive investigation of perinatal death. PMID- 26155792 TI - Antitumor and antimetastatic activities of chloroform extract of medicinal mushroom Cordyceps taii in mouse models. AB - BACKGROUND: Cordyceps taii, an entomogenous fungus native to south China, is a folk medicine with varieties of pharmacological activities including anticancer effect. To validate the ethnopharmacological claim against cancer, the antitumor and antimetastatic activities of chloroform extract of C. taii (CFCT) were investigated in vivo. METHODS: The in vitro cytotoxic activities of CFCT against human lung cancer (A549) and gastric cancer (SGC-7901) cells were evaluated using the Sulforhodamine B (SRB) assay. In vivo anti tumor and antimetastatic activities, Kunming mice bearing sarcoma 180 and C57BL/6 mice bearing melanoma B16F10 were employed, respectively. The antitumor effects of CFCT were completely evaluated on the basis of the tumor weight, survival time, histologic analysis, and immune organ indices. The histopathological change, metastatic foci and malignant melanoma specific marker HMB45 in the lung tissue were detected for the evaluation of the antimetastatic activity of CFCT. RESULTS: CFCT exhibited dose- and time-dependent cytotoxicities against A549 and SGC-7901 cells with the IC50 values of 30.2 and 65.7 MUg/mL, respectively. Furthermore, CFCT at a dose of 50 or 100 mg/kg could significantly inhibit the tumor growth in vivo and prolonged the survival time in two different models as compared with the model group, especially when combined with the CTX at a low dose rate. And it also increased spleen index of Kunming mice and thymus index of C57BL/6 mice. Meanwhile, histologic analysis illustrated that CFCT alone or in combination with CTX could induce tumor tissue necrosis of both models. In addition, CFCT at a dose of 50 or 100 mg/kg inhibited the lung metastasis of melanoma B16F10 in tumor-bearing C57BL/6 mice. The antimetastatic effect was also observed when CFCT was used in combination with CTX. In comparison to any other groups, CFCT at a dose of 100 mg/kg could effectively enhance the GSH-Px activities of various tissues in tumor bearing C57BL/6 mice. CONCLUSIONS: These findings demonstrate that CFCT has potent in vivo antitumor and antimetastatic activities, and may be helpful to the development of anticancer chemopreventive agents from C. taii. PMID- 26155794 TI - The health and economic benefits of reducing intimate partner violence: an Australian example. AB - BACKGROUND: Intimate partner violence (IPV) has important impacts on the health of women in society. Our aim was to estimate the health and economic benefits of reducing the prevalence of IPV in the 2008 Australian female adult population. METHODS: Simulation models were developed to show the effect of a 5 percentage point absolute feasible reduction target in the prevalence of IPV from current Australian levels (27%). IPV is not measured in national surveys. Levels of psychological distress were used as a proxy for exposure to IPV since psychological conditions represent three-quarters of the disease burden from IPV. Lifetime cohort health benefits for females were estimated as fewer incident cases of violence-related disease and injury; deaths; and Disability Adjusted Life Years (DALYs). Opportunity cost savings were estimated for the health sector, paid and unpaid production and leisure from reduced incidence of IPV related disease and deaths. Workforce production gains were estimated by comparing surveyed participation and absenteeism rates of females with moderate psychological distress (lifetime IPV exposure) against high or very high distress (current IPV exposure), and valued using the friction cost approach (FCA). The impact of improved health status on unpaid household production and leisure time were modelled from time use survey data. Potential costs associated with interventions to reduce IPV were not considered. Multivariable uncertainty analyses and univariable sensitivity analyses were undertaken. RESULTS: A 5 percentage point absolute reduction in the lifetime prevalence of IPV in the 2008 Australian female population was estimated to produce 6000 fewer incident cases of disease/injury, 74 fewer deaths, 5000 fewer DALYs lost and provide gains of 926,000 working days, 371,000 days of home-based production and 428,000 leisure days. Overall, AUD371 million in opportunity cost savings could be achievable. The greatest economic savings would be home-based production (AUD147 million), followed by leisure time (AUD98 million), workforce production (AUD94 million) and reduced health sector costs (AUD38 million). CONCLUSIONS: This study contributes new knowledge about the economic impact of IPV in females. The findings provide evidence of large potential opportunity cost savings from reducing the prevalence of IPV and reinforce the need to reduce IPV in Australia, and elsewhere. PMID- 26155795 TI - The Link Between ADHD and the Risk of Sexual Victimization Among College Women: Expanding the Lifestyles/Routine Activities Framework. AB - Using data from a nationally representative sample of college women, the current study examines attention deficit hyperactivity disorder (ADHD) as a potential risk factor in the prediction of sexual victimization among college women and as an extension of the lifestyles/routine activities framework. The findings indicate that college women with ADHD experienced sexual victimization at significantly higher rates than college women without ADHD. Furthermore, ADHD emerged as a significant predictor of sexual victimization across models. The lifestyles/routine activities theory also received general support, particularly for the concepts of exposure, proximity, and guardianship. This research suggests that other risk factors outside the lifestyles/routine activities framework are important in the prediction of sexual victimization in college women. PMID- 26155796 TI - Health-related quality of life is impaired in primary hyperparathyroidism and significantly improves after surgery: a prospective study using the 15D instrument. AB - Health-related quality of life (HRQoL) is frequently impaired in primary hyperparathyroidism (PHPT) but it is unclear if surgery is beneficial. The objective was to prospectively assess HRQoL in PHPT (n=124) with the 15D instrument before and after surgery, to compare it with that of a comparable sample of the general population (n=4295), and search for predictors of HRQoL and its change. HRQoL, and clinical and laboratory parameters were measured before and at 6 and 12 months after surgery. Regression techniques were used to search for predictors of HRQoL and gains from treatment. Before surgery, PHPT patients had significantly lower mean 15D score compared to controls (0.813 vs 0.904, P<0.001). Excretion, mental function, discomfort and symptoms, distress, depression, vitality, and sexual activity were most impaired (all P<0.001). Number of medications (P=0.001) and subjective symptoms (P<0.05) but not calcium or parathyroid hormone (PTH) predicted impaired HRQoL. Serum 25-hydroxyvitamin D (25OHD) was of borderline significance (P=0.051). Compared to baseline, mean 15D score improved significantly 6 months after surgery (0.813 vs 0.865, P<0.001) and the effect sustained at 1 year (0.878, P<0.001). The improvement was clinically important in 77.4% of patients (P<0.001). Educational level independently predicted improvement (P<0.005). HRQoL is severely impaired in PHPT but improves significantly after surgery. The 15D is a sensitive tool for assessing HRQoL and recognizing patients likely to benefit from surgery. PMID- 26155797 TI - To Punish or Not to Punish-That Is the Question. AB - Attitudes toward punishment have long been of interest to policymakers, researchers, and criminal justice practitioners. The current study examined the relationship between academic education in criminology and attitudes toward punishment among 477 undergraduate students in three subgroups: police officers, correctional officers, and criminology students who were not employed by the criminal justice system (CJS). Our main findings concluded that (a) punitive attitudes of the correctional officers and police officers at the beginning of their academic studies were harsher than those of the criminology and criminal justice students who were not employed by the CJS, (b) punitive attitudes of the correctional officers at the end of their academic studies were less severe than their first-year counterparts, (c) fear of crime was higher among women than among men, and (d) the strongest predictor of punitive attitudes was a firm belief in the principles of the classical and labeling theories (beyond group). Implications of these results are discussed. PMID- 26155798 TI - 'Photographic negative of pulmonary oedema': a classical radiographic pattern of chronic eosinophilic pneumonia. PMID- 26155799 TI - Noncommunicable Diseases of Major Public Health Interest and Prevention. AB - Noncommunicable diseases (NCDs; mainly cancer, cardiovascular diseases, diabetes, and chronic respiratory diseases) are now responsible for more than 35 million deaths per annum in the world; more than 80% of these deaths occur in low- and middle-income countries. Dramatic worldwide changes in lifestyle and in the prevalence and incidence of major chronic diseases lends credence to the causative role of modifiable risk factors. For the elucidation of modifiable risk factors, large-scale prospective cohort studies with biobanks often combined in consortia are of paramount importance. Associations between selected risk factors and development of NCDs will be reviewed. In addition to the contribution of treatment, even larger proportions of NCDs can be prevented had risk factors been reduced to the optimum levels or eliminated. Individual-based approaches should be complemented by administrative regulations. PMID- 26155800 TI - Extended in vitro maturation affects gene expression and DNA methylation in bovine oocytes. AB - To mimic post-ovulatory ageing, we have extended the in vitro maturation (IVM) phase to 48 h and examined effects on (i) developmental potential, (ii) expression of a panel of developmentally important genes and (iii) gene-specific epigenetic marks. Results were compared with the 24 h IVM protocol (control) usually employed for bovine oocytes. Cleavage rates and blastocyst yields were significantly reduced in oocytes after extended IVM. No significant differences were observed in the methylation of entire alleles in oocytes for the genes bH19, bSNRPN, bZAR1, bOct4 and bDNMT3A. However, we found differentially methylated CpG sites in the bDNMT3Ls locus in oocytes after extended IVM and in embryos derived from them compared with controls. Moreover, embryos derived from the 48 h matured oocyte group were significantly less methylated at CpG5 and CpG7 compared with the 24 h group. CpG7 was significantly hypermethylated in embryos produced from the control oocytes, but not in oocytes matured for 48 h. Furthermore, methylation for CpG5-CpG8 of bDNMT3Ls was significantly lower in oocytes of the 24 h group compared with embryos derived therefrom, whereas no such difference was found for oocytes and embryos of the in vitro aged group. Expression of most of the selected genes was not affected by duration of IVM. However, transcript abundance for the imprinted gene bIGF2R was significantly reduced in oocytes analyzed after extended IVM compared with control oocytes. Transcript levels for bPRDX1, bDNMT3A and bBCLXL were significantly reduced in 4- to 8-cell embryos derived from in vitro aged oocytes. These results indicate that extended IVM leads to ageing-like alterations and demonstrate that epigenetic mechanisms are critically involved in ageing of bovine oocytes, which warrants further studies into epigenetic mechanisms involved in ageing of female germ cells, including humans. PMID- 26155801 TI - Age- and Sex-Specific Burden of Cardiovascular Disease Attributable to 5 Major and Modifiable Risk Factors in 10 Asian Countries of the Western Pacific Region. AB - Cardiovascular disease (CVD) is the leading cause of mortality worldwide, causing an estimated 18 million deaths annually. Much of the burden of CVD resides in lower- and middle-income countries, particularly those Asian countries comprising the Western Pacific Region. Epidemiological studies have convincingly shown that up to 90% of all CVD can be explained by a small number of modifiable risk factors, including blood pressure, smoking, diabetes, total cholesterol and excess body weight. However, the relationship between these risk factors and coronary artery disease and stroke often differ by age and sex, and yet these differences are often overlooked in burden of disease estimations. As such, that can result in either an over- or under-estimation of the disease burden in specific population subgroups, which may affect resource allocation of healthcare. In this review, we derive the most reliable and previously unpublished estimates of the age- and sex-specific burden of vascular disease attributable to the aforementioned risk factors for 10 of the most populous Asian countries in the Western Pacific Region. Understanding how the burden of vascular disease is distributed within and between populations is crucial for developing appropriate health policies and effective treatment strategies, particularly in resource-poor settings. PMID- 26155802 TI - Coexistent Types of Atrioventricular Nodal Re-Entrant Tachycardia: Implications for the Tachycardia Circuit. AB - BACKGROUND: There is evidence that atypical fast-slow and typical atrioventricular nodal re-entrant tachycardia (AVNRT) do not use the same limb for fast conduction, but no data exist on patients who have presented with both typical and atypical forms of this tachycardia. We compared conduction intervals during typical and atypical AVNRT that occurred in the same patient. METHODS AND RESULTS: In 20 of 1299 patients with AVNRT, both typical and atypical AVNRT were induced at electrophysiology study by pacing maneuvers and autonomic stimulation or occurred spontaneously. The mean age of the patients was 47.6+/-10.9 years (range, 32-75 years), and 11 patients (55%) were women. Tachycardia cycle lengths were 368.0+/-43.1 and 365.8+/-41.1 ms, and earliest retrograde activation was recorded at the coronary sinus ostium in 60% and 65% of patients with typical and atypical AVNRT, respectively. Thirteen patients (65%) displayed atypical AVNRT with fast-slow characteristics. By comparing conduction intervals during slow fast and fast-slow AVNRT in the same patient, fast pathway conduction times during the 2 types of AVNRT were calculated. The mean difference between retrograde fast pathway conduction during slow-fast AVNRT and anterograde fast pathway conduction during fast-slow AVNRT was 41.8+/-39.7 ms and was significantly different when compared with the estimated between-measurement error (P=0.0055). CONCLUSIONS: Our data provide further evidence that typical slow-fast and atypical fast-slow AVNRT use different anatomic pathways for fast conduction. PMID- 26155803 TI - Intramural Ventricular Recording and Pacing in Patients With Refractory Ventricular Tachycardia: Initial Findings and Feasibility With a Retractable Needle Catheter. AB - BACKGROUND: Ablation of ventricular arrhythmias (VA) can be limited by intramural substrate not amenable to endocardial or epicardial ablation. Feasibility of irrigated needle ablation has been shown, but optimal means of identifying targets is not clear. We analyzed intramural needle electrograms in relation to endocardial electrograms. METHODS AND RESULTS: Eight sequential patients (mean age, 56 years) who had failed 1 to 4 prior ablations underwent irrigated needle ablation were included. At selected sites, the needle was advanced into the myocardium. Bipolar and unipolar electrograms from the needle and catheter tip were analyzed. The needle was deployed at 75 sites with suspected intramural substrate among 2309 mapping sites. Intramural bipolar electrogram amplitude and duration correlated closely with endocardial electrograms, but were greater in amplitude and duration (1.5+/-1.4 versus 0.6+/-0.5 mV and 131+/-66 versus 112+/ 51 ms; P=0.001 for both). During sinus rhythm intramural late potentials tended to be more common than endocardial late potentials (53.6% versus 35.7%; P=0.12). Intramural electrograms during VA preceded endocardial electrograms (-29+/-34 versus -15+/-21 ms; P=0.001). Irrigated needle ablation terminated VA at 12 of 28 sites with ablation during VA. Termination site needle electrograms tended to be earlier than nontermination sites (-54+/-37 versus -36+/-33 ms pre-QRS; P=0.15). Pacemapping from the needle at 19 sites matched the VA at 18 and showed stimulus to QRS of 60+/-51 ms. CONCLUSIONS: Recordings from intramural needle may be useful for selecting ablation targets during ventricular tachycardia and for substrate mapping. Further study is needed to develop methods to guide selection of optimal sites for needle deployment and ablation. PMID- 26155804 TI - Preparation and Characterization of Dictyophora indusiata Polysaccharide-Zinc Complex and Its Augmented Antiproliferative Activity on Human Cancer Cells. AB - Dictyophora indusiata polysaccharide (DP1) was successfully chelated with zinc chloride to achieve its enhanced antiproliferative activity. The obtained DP1-Zn complex showed significant antiproliferative activity (18.1 +/- 2.84% viability of MCF-7 cells at 250 MUg/mL) on a group of human cancer cell lines through induction of apoptosis. The pro-apoptotic action of DP1-Zn was confirmed by morphological changes including chromatin condensation, DNA breakage, and S phase cell cycle arrest in human breast adenocarcinoma cells (MCF-7). The DP1-Zn induced apoptotic pathways were characterized by the activation of caspases-3, 8, and -9, mitochondrial dysfunction, and reactive oxygen species (ROS) overproduction (305 +/- 7.06% production of control at 250 MUg/mL). This study suggested that DP1-Zn can be developed as a candidate for cancer treatment and prevention, especially human breast adenocarcinoma. PMID- 26155805 TI - Flow and Microwave-Assisted Synthesis of N-(Triethylene glycol)glycine Oligomers and Their Remarkable Cellular Transporter Activities. AB - Peptidomimetics, such as oligo-N-alkylglycines (peptoids), are attractive alternatives to traditional cationic cell-penetrating peptides (such as R9) due to their robust proteolytic stability and reduced cellular toxicity. Here, monomeric N-alkylglycines, incorporating amino-functionalized hexyl or triethylene glycol (TEG) side chains, were synthesized via a three-step continuous-flow reaction sequence, giving the monomers N-Fmoc-(6-Boc aminohexyl)glycine and N-Fmoc-((2-(2-Boc-aminoethoxy)ethoxy)ethyl)glycine in 49% and 41% overall yields, respectively. These were converted into oligomers (5, 7, and 9-mers) using an Fmoc-based solid-phase protocol and evaluated as cellular transporters. Hybrid oligomers, constructed of alternating units of the aminohexyl and amino-TEG monomers, were non-cytotoxic and exhibited remarkable cellular uptake activity compared to the analogous fully TEG or lysine-like compounds. PMID- 26155806 TI - [Classifying Ontology towards an Application for Radiological Technology]. AB - This study aims to grasp the target area of the literature on ontology and to apply it in radiological technology. We used Google scholar to search the literature containing the keyword "ontology". Our search identified and extracted 162,381 words from 29 manuscripts and used the 8,706 nouns excluding duplicates as individual variable. Using a cluster analysis, we categorized the documents to one of the following five classifications: (1) "Systematization of vocabulary by text mining", (2) "Hierarchy of language information", (3) "Conceptualization of situation", (4) "Standardization of lexical information", and (5) "Visualization of the concepts related to the problem". We propose that the terminologies in (2), (4), and (5) cluster can be used in radiological technology field. PMID- 26155807 TI - [Development of an Optimizing Program of Scanning Parameters for Double Inversion Recovery MRI]. AB - The purpose of this study was to develop an optimizing program of scanning parameters for double inversion recovery (DIR) MRI. The optimization algorithm consists of the following steps: (1) obtaining the initial parameters (TR, TE, and T1 values of the two attenuated tissues); (2) iterative calculation for minimization of errors; and (3) determination of the optimized TI(1st) and TI(2nd). To evaluate the developed algorithm, we performed the phantom and simulation studies using the phantoms which were imitated T1 values of white and gray matters and cerebrospinal fluid. In addition, white matter attenuated inversion recovery (WAIR) and gray matter attenuated inversion recovery (GAIR) images were obtained by optimized scan parameters in one volunteer. The developed algorithm could calculate the optimized TI(1st) and TI(2nd) values at once. Results of summation of signal intensity (SI) of two attenuated tissues shows that the SI of the two tissues were well-attenuated using the theoretical values which were calculated using the developed algorithm. The correlation coefficient of the SI of the phantom of the gray matter between actual and simulation measurements was r=0.997. The SI obtained by actual measurements well correlated with the SI obtained by the simulation measurements. The WAIR and GAIR images in the volunteer were well enhanced gray or white matters. We thus conclude that it is possible to calculate the optimized parameters for the DIR-MRI using the developed algorithm. PMID- 26155808 TI - [The Impact That SPECT Collection Angle and Collection Orbit Gives to an Image: Myocardial Digital Phantom Study]. AB - PURPOSE: We evaluated the effect that collection angle and collection orbit condition gave to an image quantitatively by simulating the single photon emission computed tomography (SPECT) system. METHOD: Using the Software Package of the Nuclear Medicine Data Processor for Research, we performed making of the myocardial digital phantom, three ways of different simulation of the collection angle and collection orbit, and making of reference of the uniform picture element level. We calculated NMSE for uniformity evaluation and calculated myocardial thickness full width at half maximum (FWHM) for a spatial resolution evaluation. RESULTS: 360 degrees circular orbit collection had best uniformity. 180 degrees noncircular orbit collection had best spatial resolution. CONCLUSION: By using the digital phantom, we focused on only collection angle and collection orbit condition, and focused on two indexes of the uniformity and the spatial resolution and were able to show a quantitative index. PMID- 26155809 TI - [Examination of Whole Treatment Time Required for Multiple Metastatic Brain Tumors in Cobalt-60 Stereotactic Radiosurgery Procedures]. AB - A study was conducted to clarify the time required for each treatment procedure and whole treatment time from treatment records of 124 patients with metastatic brain tumors treated by Gamma Knife (GK) Perfexion during the period from June 2013 to November 2014. GK treatment procedure is as follows: a skull frame is attached to the patient's head, contrast-enhanced magnetic resonance (MR) imaging is acquired for treatment planning, the skull shape is provided by manual measurement, appropriate dose and dose distribution are determined for the target, irradiation is executed according to completed treatment plan, and the frame is removed after irradiation. As the results, it took 15.1+/-12.4 min for frame fixation, 30.1+/-11.5 min for MR scan, 5.0+/-1.0 min for skull measurement, 72.5+/-42.4 min for treatment planning, 91.3+/-56.1 min for irradiation, 99.2+/ 60.6 min as treatment time, and 5.6+/-5.1 min for frame removal. In conclusion, it was shown that GK Perfexion stereotactic radiosurgery has high treatment efficiency and less burden on patients. PMID- 26155810 TI - [10. Application of Monte Carlo Simulation to Radiological Technology -No.1 Focus on Photon for Radiation Therapy]. PMID- 26155811 TI - [7. Treatment of Cerebrovascular Disease]. PMID- 26155812 TI - [New Trend in Medical Image Management]. PMID- 26155813 TI - Validity of Ski Skating Center-of-Mass Displacement Measured by a Single Inertial Measurement Unit. AB - In regard to simplifying motion analysis and estimating center of mass (COM) in ski skating, this study addressed 3 main questions concerning the use of inertial measurement units (IMU): (1) How accurately can a single IMU estimate displacement of os sacrum (S1) on a person during ski skating? (2) Does incorporating gyroscope and accelerometer data increase accuracy and precision? (3) Moreover, how accurately does S1 determine COM displacement? Six world-class skiers roller-ski skated on a treadmill using 2 different subtechniques. An IMU including accelerometers alone (IMU-A) or in combination with gyroscopes (IMU-G) were mounted on the S1. A reflective marker at S1, and COM calculated from 3D full-body optical analysis, were used to provide reference values. IMU-A provided an accurate and precise estimate of vertical S1 displacement, but IMU-G was required to attain accuracy and precision of < 8 mm (root-mean-squared error and range of displacement deviation) in all directions and with both subtechniques. Further, arm and torso movements affected COM, but not the S1. Hence, S1 displacement was valid for estimating sideways COM displacement, but the systematic amplitude and timing difference between S1 and COM displacement in the anteroposterior and vertical directions inhibits exact calculation of energy fluctuations. PMID- 26155814 TI - Readability of Information Related to the Parenting of a Child With a Cleft. AB - BACKGROUND: Many parents look to various sources for information about parenting when their child has a cleft lip and/or palate. More than 8 million Americans perform health-related searches every day on the World Wide Web. Furthermore, a significant number of them report feeling "overwhelmed" by the language and content of the information. OBJECTIVE: The purpose of this study is to determine the readability of information related to parenting a child with cleft lip and/or palate. It was hypothesized that the readability of such materials would be at a level higher than 6th grade. METHODS: In February of 2012, a Web-based search was conducted using the search engine Google for the terms "parenting cleft lip and palate." RESULTS: A total of 15 websites, 7 books, and 8 booklets/factsheets (N=30) entered the readability analysis. Flesch-Kincaid Grade Level, Fog Scale Level, and Simple Measure of Gobbledygook (SMOG) index scores were calculated. The reading level of the websites and books ranged from 8th to 9th and 9th to10th grade, respectively. The average reading level of the booklets/factsheets was 10th grade. Overall, the mean readability of the media resources analyzed was considered "hard to read." No statistically significant mean difference was found for the readability level across websites, books, and booklets/factsheets (Kruskal-Wallis test, significance level .05). CONCLUSIONS: When considering websites, books, booklets, and factsheets analyzed, the average readability level was between 8th and 10th grade. With the US national reading level average at 8th grade and the general recommendation that health-related information be written at a 6th grade level, many parents may find the text they are reading too difficult to comprehend. Therefore, many families might be missing out on the opportunity to learn parenting practices that foster optimal psychosocial development of their children. PMID- 26155815 TI - Health Benefits of Daily Walking on Mortality Among Younger-Elderly Men With or Without Major Critical Diseases in the New Integrated Suburban Seniority Investigation Project: A Prospective Cohort Study. AB - BACKGROUND: Regular physical activity contributes to the prevention of cancer, cardiovascular disease, and other chronic diseases. However, the frequency of physical activity often declines with age, particularly among the elderly. Thus, we investigated the effects of daily walking on mortality among younger-elderly men (65-74 years) with or without major critical diseases (heart disease, cerebrovascular disease, or cancer). METHODS: We assessed 1239 community-dwelling men aged 64/65 years from the New Integrated Suburban Seniority Investigation Project. We estimated hazard ratios (HRs) of all-cause mortality and 95% confidence intervals (CIs) according to daily walking duration and adjusted for potential confounders, including survey year, marital status, work status, education, smoking and drinking status, BMI, regular exercise, regular sports, sleeping time, medical status, disease history, and functional capacity. RESULTS: For men without critical diseases, mortality risk declined linearly with increased walking time after adjustment for confounders (Ptrend = 0.018). Walking >=2 hours/day was significantly associated with lower all-cause mortality (HR 0.49; 95% CI, 0.27-0.90). For men with critical diseases, walking 1-2 hours/day showed a protective effect on mortality compared with walking <0.5 hours/day after adjustment for confounders (HR 0.29; 95% CI, 0.06-1.20). Walking >=2 hours/day showed no benefit on mortality in men with critical diseases, even after adjustment for confounders. CONCLUSIONS: Different duration of daily walking was associated with decreased mortality for younger-elderly men with or without critical diseases, independent of sociodemographic and lifestyle factors, BMI, medical status, disease history, and functional capacity. Incorporating regular walking into daily lives of younger-elderly men may improve longevity and successful aging. PMID- 26155816 TI - Metrics for the Human Proteome Project 2015: Progress on the Human Proteome and Guidelines for High-Confidence Protein Identification. AB - Remarkable progress continues on the annotation of the proteins identified in the Human Proteome and on finding credible proteomic evidence for the expression of "missing proteins". Missing proteins are those with no previous protein-level evidence or insufficient evidence to make a confident identification upon reanalysis in PeptideAtlas and curation in neXtProt. Enhanced with several major new data sets published in 2014, the human proteome presented as neXtProt, version 2014-09-19, has 16,491 unique confident proteins (PE level 1), up from 13,664 at 2012-12 and 15,646 at 2013-09. That leaves 2948 missing proteins from genes classified having protein existence level PE 2, 3, or 4, as well as 616 dubious proteins at PE 5. Here, we document the progress of the HPP and discuss the importance of assessing the quality of evidence, confirming automated findings and considering alternative protein matches for spectra and peptides. We provide guidelines for proteomics investigators to apply in reporting newly identified proteins. PMID- 26155817 TI - Cancer patients' emotional distress, coping styles and perception of doctor patient interaction in European cancer settings. AB - OBJECTIVE: As a part of a European study, we cross-culturally examined the rate of emotional distress and maladaptive coping and their association with cancer patients' satisfaction with their interactions with the physician responsible for their care. METHODS: Cancer patients (n = 302) from one Middle European (Austria) and two Southern European (Italy, Spain) countries completed the NCCN Distress Thermometer (DT), the Mini-Mental Adjustment to Cancer (Mini-MAC) Anxious Preoccupation (AP) and Hopelessness (H) sub-scales, and the Physician Patient Satisfaction with Doctors Questionnaire (PSQ). RESULTS: The prevalence of emotional distress (DT caseness) was 60% (26.1% mild, 18.8% moderate, and 14.9% severe distress). Maladaptive coping (Mini-MAC cases) was found in 22.8% (hopeless cases), and 22.5% (anxious preoccupation cases). PSQ-MD was significantly correlated with Mini-MAC/H and Mini-Mac/AP, while PSQ-PS was negatively correlated with Mini-MAC/H. DT cases and those with higher levels of hopelessness reported higher scores on PSQ-MD and lower on PSQ-PS than non-cases. Some differences were found between countries both as far as patients' coping and perception of the interaction with doctors. In hierarchical multiple regression analysis, after adjusting for socio-demographic and medical variables, Mini-MAC/H significantly predicted the scores on PSQ-MD (positive direction) and PSQ-PS (negative direction). SIGNIFICANCE OF RESULTS: The study confirms that about one out of three cancer patients have moderate to high level of emotional distress and about one out of four, clinically significant maladaptive coping. Also, patients showing hopelessness and distress tended to perceive their doctors as both disengaged and less supportive. These results highlights the need for physicians to monitor their patient's level of distress and coping mechanisms and to adjust their own relational and communication style according to patients' psychological condition. Also, cross-cultural issues should be taken into account when exploring psychosocial variables and cancer patients' perception of and satisfaction with the interaction with their doctors. PMID- 26155818 TI - Depression among patients with tuberculosis: determinants, course and impact on pathways to care and treatment outcomes in a primary care setting in southern Ethiopia--a study protocol. AB - INTRODUCTION: Depression is commonly comorbid with chronic physical illnesses and is associated with a range of adverse clinical outcomes. Currently, the literature on the role of depression in determining the course and outcome of tuberculosis (TB) is very limited. AIM: Our aim is to examine the relationship between depression and TB among people newly diagnosed and accessing care for TB in a rural Ethiopian setting. Our objectives are to investigate: the prevalence and determinants of probable depression, the role of depression in influencing pathways to treatment of TB, the incidence of depression during treatment, the impact of anti-TB treatment on the prognosis of depression and the impact of depression on the outcomes of TB treatment. METHODS AND ANALYSIS: We will use a prospective cohort design. 703 newly diagnosed cases of TB (469 without depression and 234 with depression) will be consecutively recruited from primary care health centres. Data collection will take place at baseline, 2 and 6 months after treatment initiation. The primary exposure variable is probable depression measured using the Patient Health Questionnaire-9. Outcome variables include: pathways to treatment, classical outcomes for anti-TB treatment quality of life and disability. Descriptive statistics, logistic regression and multilevel mixed effect analysis will be used to test the study hypotheses. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Institutional Review Board (IRB) of the College of Health Sciences, Addis Ababa University. Findings will be disseminated through scientific publications, conference presentations, community meetings and policy briefs. ANTICIPATED IMPACT: Findings will contribute to a sparse evidence base on comorbidity of depression and TB. We hope the dissemination of findings will raise awareness of comorbidity among clinicians and service providers, and contribute to ongoing debates regarding the delivery of mental healthcare in primary care in Ethiopia. PMID- 26155819 TI - Evaluation of the fidelity of an interactive face-to-face educational intervention to improve general practitioner management of back pain. AB - OBJECTIVES: Implementation intervention effects can only be fully realised and understood if they are faithfully delivered. However the evaluation of implementation intervention fidelity is not commonly undertaken. The IMPLEMENT intervention was designed to improve the management of low back pain by general medical practitioners. It consisted of a two-session interactive workshop, including didactic presentations and small group discussions by trained facilitators. This study aimed to evaluate the fidelity of the IMPLEMENT intervention by assessing: (1) observed facilitator adherence to planned behaviour change techniques (BCTs); (2) comparison of observed and self-reported adherence to planned BCTs and (3) variation across different facilitators and different BCTs. DESIGN: The study compared planned and actual, and observed versus self-assessed delivery of BCTs during the IMPLEMENT workshops. METHOD: Workshop sessions were audiorecorded and transcribed verbatim. Observed adherence of facilitators to the planned intervention was assessed by analysing the workshop transcripts in terms of BCTs delivered. Self-reported adherence was measured using a checklist completed at the end of each workshop session and was compared with the 'gold standard' of observed adherence using sensitivity and specificity analyses. RESULTS: The overall observed adherence to planned BCTs was 79%, representing moderate-to-high intervention fidelity. There was no significant difference in adherence to BCTs between the facilitators. Sensitivity of self-reported adherence was 95% (95% CI 88 to 98) and specificity was 30% (95% CI 11 to 60). CONCLUSIONS: The findings suggest that the IMPLEMENT intervention was delivered with high levels of adherence to the planned intervention protocol. TRIAL REGISTRATION NUMBER: The IMPLEMENT trial was registered in the Australian New Zealand Clinical Trials Registry, ACTRN012606000098538 (http://www.anzctr.org.au/trial_view.aspx?ID=1162). PMID- 26155821 TI - Considerations when using pharmacokinetic/pharmacodynamic modeling to determine the effectiveness of simple analgesics in children. AB - INTRODUCTION: Assessment of analgesic drugs includes comparative studies to other analgesics and local anesthesia blockade, number needed to treat estimates and opioid sparing descriptions. An additional methodology is to define the concentration-response relationship using pharmacokinetic/pharmacodynamic (PK/PD) modeling. AREAS COVERED: A concentration-response relationship allows analgesic effect comparison between drugs for different acute pain types. Covariates such as size, age and organ function impact greatly on PK in children. The cumulative effect of confounding factors (e.g., pharmacogenetics, placebo and changes in baseline pain over time) complicates PD. Other factors (outcome measures, method of measurement, failure to account for study attrition) impact on outcome. Population PK/PD modeling approaches allow us to account for these various factors to some extent. EXPERT OPINION: Nonlinear mixed effects models help interpret analgesic data and their use is increasing. The PK is relatively well understood. The next investigative step will involve investigation into covariate effects for PD. Mathematical functions for both placebo models and dropout models are well described and should be incorporated into analgesic effectiveness studies that investigate a range of doses. Improvements in pain assessment tools and a greater understanding of pharmacogenomics factors will help individualize analgesic therapy. PMID- 26155820 TI - Prospective cohort study protocol to describe the transfer of patients from intensive care units to hospital wards. AB - INTRODUCTION: The transfer of patient care between the intensive care unit (ICU) and the hospital ward is associated with increased risk of medical error and adverse events. This study will describe patient transfer from ICU to hospital ward by documenting (1) patient, family and provider experiences related to ICU transfer, (2) communication between stakeholders involved in ICU transfer, (3) adverse events that follow ICU transfer and (4) opportunities to improve ICU to hospital ward transfer. METHODS: This is a mixed methods prospective observational study of ICU to hospital ward transfer practices in 10 ICUs across Canada. We will recruit 50 patients at each site (n=500) who are transferred from ICU to hospital ward, and distribute surveys to enrolled patients, family members, and healthcare providers (ICU and ward physicians and nurses) after patient transfer. A random sample of 6 consenting study participants (patients, family members, healthcare providers) from each study site (n=60) will be offered an opportunity to participate in interviews to further describe stakeholders' experience with ICU to hospital ward transfer. We will abstract information from patient health records to identify clinical data and use of transfer tools, and identify adverse events that are related to the transfer. ETHICS AND DISSEMINATION: Research ethics board approval has been obtained at the coordinating study centre (UofC REB13-0021) and 5 study sites (UofA Pro00050646; UBC-PHC H14-01667; Sunnybrook 336-2014; QCH 14-07; Sherbrooke 14-172). Dissemination of the findings will provide a comprehensive description of transfer from ICU to hospital ward in Canada including the uptake of validated or local transfer tools, a conceptual framework of the experiences and needs of stakeholders in the ICU transfer process, a summary of adverse events experienced by patients after transfer from ICU to hospital ward, and opportunities to guide quality improvement efforts. PMID- 26155822 TI - New flavonoid from Patrinia villosa. AB - CONTEXT: Patrinia villosa (Thunb.) Juss (Valerianaceae) is an important ancient herbal medicine widely used for inflammation, wound healing, and abdominal pain. But little is known of the phytochemical constituents of this herbal plant. OBJECTIVE: The objective of this study is to isolate and identify the bioactive components from P. villosa. MATERIALS AND METHODS: A 70% EtOH extract of P. villosa was subjected to normal-phase silica, ODS silica gel column chromatography, and semi-preparative HPLC chromatography after partitioned successively with light petroleum, dichloromethane and n-BuOH. Chemical structures of the compounds were elucidated by spectroscopic methods including UV, 1D-NMR, 2D-NMR, HR-ESI-MS, and CD spectra. The cytotoxic activity of the new component was determined with the SMMC-7721 cell line using the MTT method after incubation for 48 h. RESULTS: A new flavonoid named patriniaflavanone A (1) along with four known compounds was isolated from P. villosa. The four known compounds were identified as luteolin 7-O-glucuronide-6"-methyl ester (2), p hydroxyphenylacetic acid methyl ester (3), trans-caffeic acid (4), and trans caffeic acid methylate (5) by comparison of their spectral data with the reported data. The IC50 value of patriniaflavanone A (1) on SMMC-7721 was 61.27 MUM. DISCUSSION AND CONCLUSION: This is the first report on the isolation and identification of patriniaflavanone A (1), and compounds 2-5 were isolated for the first time from the title plant. Patriniaflavanone A (1) exhibited moderate cytotoxic activity. PMID- 26155823 TI - Effects of high heeled shoes wearing experience and heel height on human standing balance and functional mobility. AB - This study aimed to examine the effects of high heeled shoes (HHS) wearing experience and heel height on human standing balance and functional mobility. Thirty young and healthy females (ten experienced and twenty inexperienced HHS wearers) participated in a series of balance tests when they wore shoes of four different heel heights: 1 cm (flat), 4 cm (low), 7 cm (medium) and 10 cm (high). Experimental results show that regardless of the wearing experience, the heel elevation induces more effort from lower limb muscles (particularly calf muscles) and results in worse functional mobility starting at 7 cm heel height. While the heel height increased to 10 cm, the standing balance also becomes worse. Experienced HHS wearers do not show significantly better overall performance on standing balance and functional mobility than inexperienced controls, even though they have better directional control (76.8% vs. 74.4%) and larger maximum excursion (93.3% vs. 89.7%). To maintain standing balance, experienced wearers exert less effort on tibialis anterior, vastus lateralis and erector spinae muscles at the cost of more intensive effort from gastrocnemius medialis muscle. PRACTITIONER SUMMARY: Many women wear high heeled shoes (HHS) to increase female attractiveness. This study shows that HHS induce more muscular effort and worse human standing balance and functional mobility, especially when heel height reaches 10 cm. HHS wearing experience only provides certain advantages to wearers on limits of stability in terms of larger maximum excursion and better directional control. PMID- 26155824 TI - Urine survivin, E-cadherin and matrix metalloproteinases as novel biomarkers in children with chronic kidney disease. AB - CONTEXT: Epithelial-mesenchymal transition (EMT) leads to renal fibrosis and chronic kidney disease (CKD). OBJECTIVE: The aim of this study was to assess the usefulness of survivin, E-cadherin and metalloproteinases (MMPs) as biomarkers of CKD-related complications. MATERIAL AND METHODS: Survivin, E-cadherin, MMP-2, MMP 9 and TGFbeta1 were assessed by ELISA in 41 children with CKD stages 3 to 5 and in 23 controls. RESULTS: The serum and urine values of analyzed parameters were significantly elevated in CKD patients versus controls and correlated with each other. CONCLUSIONS: The observed parameter changes indicate apoptosis, tissue remodeling and fibrosis in CKD children. Urine survivin may become a new biomarker of kidney-specific EMT. PMID- 26155825 TI - Self-efficacy, planning, and preparatory behaviours as joint predictors of physical activity: A conditional process analysis. AB - OBJECTIVE: Planning can bridge the gap between intentions and action, but what bridges the gap between planning and action? This study helps to answer the question by disentangling the interrelationships between self-efficacy, planning and preparatory behaviours in predicting physical activity. Preparatory behaviours are tested as a working mechanism of planning. Moreover, it is tested whether the utility of preparatory behaviours depends on an individual's level of self-efficacy. METHODS: A survey assessed planning, self-efficacy and preparatory behaviours for physical activity. Adults (N = 166) provided data at two measurement points. In a longitudinal model, preparatory behaviours were specified as a mediator between planning and physical activity. Self-efficacy was specified as a possible moderator at two points in the model. RESULTS: Preparatory behaviours mediated the relationship between planning and physical activity. An interaction between self-efficacy and preparatory behaviours on physical activity was found, indicating that individuals with low self-efficacy beliefs were more active if they engaged more frequently in preparatory behaviours. CONCLUSION: Planning seems to stimulate preparatory behaviours, which in turn make future physical activity more likely. Furthermore, as performing preparatory behaviours represent a step forward towards the enactment of behavioural goals, preparatory behaviours may be particular beneficial for individuals afflicted by self-doubts regarding physical activity. PMID- 26155826 TI - Fucophlorethol C, a phlorotannin as a lipoxygenase inhibitor. AB - Fucophlorethol C, a phlorotannin, was isolated from the brown alga Colpomenia bullosa (Scyto-siphonaceae) as a novel lipoxygenase (LOX) inhibitor. It was obtained as a free form from natural origin for the first time. The compound inhibited a soybean LOX to the same extent as the known inhibitor nordihydroguaiaretic acid. PMID- 26155827 TI - Time, timing, and the treatment of diffuse large B-cell lymphoma. PMID- 26155828 TI - A population-based analysis of second malignancies among patients with myeloproliferative neoplasms in the SEER database. PMID- 26155829 TI - Cryptic Hepatitis B and E in Patients With Acute Hepatitis of Unknown Etiology. AB - BACKGROUND: Up to 30% of acute viral hepatitis has no known etiology. To determine the disease etiology in patients with acute hepatitis of unknown etiology (HUE), serum specimens were obtained from 38 patients residing in the United Kingdom and Vietnam and from 26 healthy US blood donors. All specimens tested negative for known viral infections causing hepatitis, using commercially available serological and nucleic acid assays. METHODS: Specimens were processed by sequence-independent complementary DNA amplification and next-generation sequencing (NGS). Sufficient material for individual NGS libraries was obtained from 12 HUE cases and 26 blood donors; the remaining HUE cases were sequenced as a pool. Read mapping was done by targeted and de novo assembly. RESULTS: Sequences from hepatitis B virus (HBV) were detected in 7 individuals with HUE (58.3%) and the pooled library, and hepatitis E virus (HEV) was detected in 2 individuals with HUE (16.7%) and the pooled library. Both HEV-positive cases were coinfected with HBV. HBV sequences belonged to genotypes A, D, or G, and HEV sequences belonged to genotype 3. No known hepatotropic viruses were detected in the tested normal human sera. CONCLUSIONS: NGS-based detection of HBV and HEV infections is more sensitive than using commercially available assays. HBV and HEV may be cryptically associated with HUE. PMID- 26155830 TI - Venous thrombotic burden and the risk of subsequent overt cancer. PMID- 26155831 TI - Assessment of female sexual function in a group of uncircumcised obese Egyptian women. AB - The aim of the present study was to assess female sexual function in an obese group (250 women) and to compare it with a control group (100 women), among 25-35 year-old uncircumcised Egyptian women, using female sexual function index (FSFI) score. FSFI total score of ? 26.55 was considered diagnostic of Female Sexual Dysfunction (FSD). The percentage of FSD in the obese group was 73.6% while it was 71% in the control group, which was statistically insignificant (P > 0.05). The difference between both groups regarding the total (FSFI) score was insignificant (P > 0.05), but arousal and satisfaction domains scores were significantly lower in the obese group. In the obese group, a strong negative correlation between body mass index and arousal, orgasm and the total FSFI score was found. Women with excessive obesity had the lowest total FSFI score. In the obese group, college graduates had the highest total scores and all domain scores of FSFI followed by high school graduates while the least educated women had the lowest scores and when these subgroups were compared, significant differences were found among them. We conclude that in uncircumcised 25-35-year-old Egyptian women, obesity is not a major detrimental factor for FSD, but it may affect some sexual domains such as arousal and satisfaction, although excessive obesity is associated with FSD. Also, educational and cultural factors may have an impact on perception of sex and pleasure. PMID- 26155833 TI - Coherent control of radiation patterns of nonlinear multiphoton processes in nanoparticles. AB - We propose a scheme for the coherent control of light waves and currents in metallic nanospheres which applies independently of the nonlinear multiphoton processes at the origin of waves and currents. We derive conditions on the external control field which enable us to change the radiation pattern and suppress radiative losses or to reduce absorption, enabling the particle to behave as a perfect scatterer or as a perfect absorber. The control introduces narrow features in the response of the particles that result in high sensitivity to small variations in the local environment, including subwavelength spatial shifts. PMID- 26155832 TI - CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells. AB - Glioblastoma (GB) remains the most aggressive primary brain malignancy. Adoptive transfer of chimeric antigen receptor (CAR)-modified immune cells has emerged as a promising anti-cancer approach, yet the potential utility of CAR-engineered natural killer (NK) cells to treat GB has not been explored. Tumors from approximately 50% of GB patients express wild-type EGFR (wtEGFR) and in fewer cases express both wtEGFR and the mutant form EGFRvIII; however, previously reported CAR T cell studies only focus on targeting EGFRvIII. Here we explore whether both wtEGFR and EGFRvIII can be effectively targeted by CAR-redirected NK cells to treat GB. We transduced human NK cell lines NK-92 and NKL, and primary NK cells with a lentiviral construct harboring a second generation CAR targeting both wtEGFR and EGFRvIII and evaluated the anti-GB efficacy of EGFR-CAR-modified NK cells. EGFR-CAR-engineered NK cells displayed enhanced cytolytic capability and IFN-gamma production when co-cultured with GB cells or patient-derived GB stem cells in an EGFR-dependent manner. In two orthotopic GB xenograft mouse models, intracranial administration of NK-92-EGFR-CAR cells resulted in efficient suppression of tumor growth and significantly prolonged the tumor-bearing mice survival. These findings support intracranial administration of NK-92-EGFR-CAR cells represents a promising clinical strategy to treat GB. PMID- 26155835 TI - Factors affecting home gardens ownership, diversity and structure: a case study from Benin. AB - BACKGROUND: Home gardens (HGs) provide perspectives for conservation of plant genetic resources while contributing to improving livelihoods. However, knowledge of local factors shaping their ownership, plant diversity (PD) and structure is still limited especially in West-Africa, where food insecurity is acute. This is critical to ensure effective mainstreaming of HGs into future biodiversity conservation and food production policies. METHODS: Socio-economic and PD data were obtained from individual interviews (n = 470) and gardens inventories (n = 235) spanning humid, sub-humid and semi-arid zones of Benin. Generalised Linear Models, Hierarchical Cluster Analysis, Principal Component Analysis and Simple Correspondence Analysis were performed to examine socio-economic characteristics (age, gender, education level and main economic activity) affecting HGs ownership, and their effect coupled with intrinsic HGs characteristics (size, age) on PD and structure within HGs, across contrasting bio-geographical regions. RESULTS: HG ownership was significantly dependent upon a complex relationship between age, gender and education level of the farmers. The probability to own HG increased with age with an early involvement in home gardening for women. Similarly, with increasing age, it was more likely to find a male owner than a female owner among the uneducated informants and those of primary school. Inversely, it was more likely to find female owner than a male owner among secondary school level or more. PD increased with increasing owner age and size of the HG. Larger and more diversified HGs were found in sub-humid and semi-arid zones while smaller and less diversified HGs were encountered in the humid zone. HGs were multi-layered. Based on the prevailing plant groups, three categories of HG were distinguished: Herb based gardens, Herb and Shrub/Trees based gardens, and Palm and Liana based gardens. Their prevalence was dependent upon bio geographical zones and HG owner socio-economic characteristics, with herbs based HGs being mainly associated to women. CONCLUSION: Results suggest effects of complex interactions between socio-economic factors on HG ownership, and influence of these effects combined with intrinsic characteristics of HGs on PD. The early involvement of women in home gardening and their particular interest in herbs and shrubs are important assets for future conservation strategies based on HG and food production. Interventions are required to interfere with declining PD in HG across generations to accommodate multiple ecosystem service benefits. PMID- 26155834 TI - Involvement of PrP(C) in kainate-induced excitotoxicity in several mouse strains. AB - The cellular prion protein (PrP(C)) has been associated with a plethora of cellular functions ranging from cell cycle to neuroprotection. Mice lacking PrP(C) show an increased susceptibility to epileptic seizures; the protein, then, is neuroprotective. However, lack of experimental reproducibility has led to considering the possibility that other factors besides PrP(C) deletion, such as the genetic background of mice or the presence of so-called "Prnp flanking genes", might contribute to the reported susceptibility. Here, we performed a comparative analysis of seizure-susceptibility using characterized Prnp(+/+) and Prnp(0/0) mice of B6129, B6.129, 129/Ola or FVB/N genetic backgrounds. Our study indicates that PrP(C) plays a role in neuroprotection in KA-treated cells and mice. For this function, PrP(C) should contain the aa32-93 region and needs to be linked to the membrane. In addition, some unidentified "Prnp-flanking genes" play a role parallel to PrP(C) in the KA-mediated responses in B6129 and B6.129 Prnp(0/0) mice. PMID- 26155836 TI - Urinary tract infection with Corynebacterium aurimucosum after urethroplasty stricture of the urethra: a case report. AB - INTRODUCTION: Corynebacteria have an important place among the commensal flora of the skin and mucous membranes. Except for Corynebacterium diphtheriae, they were once considered contaminants of mucosa. Recent publications in medical bacteriology have highlighted the importance of several species, such as C. aurimucosum. To the best of our knowledge, we report the first isolation of this strain from urine. CASE PRESENTATION: We report a case of a patient with a urinary tract infection with C. aurimucosum. We isolated this bacterium from a 52 year-old man of Wolof ethniticity (an ethnic group in Senegal, West Africa) at the regional hospital of Saint Louis, Senegal. Microscopic examination of his total urine sample showed coryneform Gram-positive bacilli associated with a high leukocyte reaction. After repeated isolation of the corynebacteria in three samples from the patient's urine, it was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The strain was susceptible to antibiotics, except for penicillin and co-trimoxazole. The potential infectious role of these commensal species in several infections should be taken into consideration. CONCLUSIONS: This case highlights the significant proportion of species in the genus Corynebacterium other than dyphteriae in the infectious process. The use of mass spectrometry for identification highlights the originality of this work and the importance of these new diagnostic tools that are unavailable in most health facilities of countries with limited resources. We share the results of our method of identification of the isolated bacteria. This case should prompt attention to these rare bacteria, which can cause severe infections. PMID- 26155837 TI - Fried phenotype of frailty: cross-sectional comparison of three frailty stages on various health domains. AB - BACKGROUND: The population ageing in most Western countries leads to a larger number of frail older people. These frail people are at an increased risk of negative health outcomes, such as functional decline, falls, institutionalisation and mortality. Many approaches are available for identifying frailty among older people. Researchers most often use Fried and colleagues' description of the frailty phenotype. The authors describe five physical criteria. Other researchers prefer a combination of measurements in the social, psychological and/or physical domains. The aim of this study is to describe the levels of social, psychological and physical functioning according to Fried's frailty stages using a large cohort of Dutch community-dwelling older people. METHODS: There were 8,684 community dwelling older people (65+) who participated in this cross-sectional study. Based on the five Fried frailty criteria (weight loss, exhaustion, low physical activity, slowness, weakness), the participants were divided into three stages: non-frail (score 0), pre-frail (score 1-2) and frail (score 3-5). These stages were related to scores in the social (social network type, informal care use, loneliness), psychological (psychological distress, mastery, self-management) and physical (chronic diseases, GARS IADL-disability, OECD disability) domains. RESULTS: 63.2% of the participants was non-frail, 28.1% pre-frail and 8.7% frail. When comparing the three stages of frailty, frail people appeared to be older, were more likely to be female, were more often unmarried or living alone, and had a lower level of education compared to their pre-frail and non-frail counterparts. The difference between the scores in the social, psychological and physical domains were statistically significant between the three frailty stages. The most preferable scores came from the non-frail group, and least preferable scores were from the frail group. For example use of informal care: non-frail 3.9%, pre-frail 23.8%, frail 60.6%, and GARS IADL-disability mean scores: non frail 9.2, pre-frail 13.0, frail 19.7. CONCLUSION: When older people were categorised according to the three frailty stages, as described by Fried and colleagues, there were statistically significant differences in the level of social, psychological and physical functioning between the non-frail, pre-frail and frail persons. Non-frail participants had consistently more preferable scores compared to the frail participants. This indicated that the Fried frailty criteria could help healthcare professionals identify and treat frail older people in an efficient way, and provide indications for problems in other domains. PMID- 26155838 TI - The diagnostic application of targeted re-sequencing in Korean patients with retinitis pigmentosa. AB - BACKGROUND: Identification of the causative genes of retinitis pigmentosa (RP) is important for the clinical care of patients with RP. However, a comprehensive genetic study has not been performed in Korean RP patients. Moreover, the genetic heterogeneity found in sensorineural genetic disorders makes identification of pathogenic mutations challenging. Therefore, high throughput genetic testing using massively parallel sequencing is needed. RESULTS: Sixty-two Korean patients with nonsyndromic RP (46 patients from 18 families and 16 simplex cases) who consented to molecular genetic testing were recruited in this study and targeted exome sequencing was applied on 53 RP-related genes. Causal variants were characterised by selecting exonic and splicing variants, selecting variants with low allele frequency (below 1 %), and discarding the remaining variants with quality below 20. The variants were additionally confirmed by an inheritance pattern and cosegregation test of the families, and the rest of the variants were prioritised using in-silico prediction tools. Finally, causal variants were detected from 10 of 18 familial cases (55.5 %) and 7 of 16 simplex cases (43.7 %) in total. Novel variants were detected in 13 of 20 (65 %) candidate variants. Compound heterozygous variants were found in four of 7 simplex cases. CONCLUSION: Panel-based targeted re-sequencing can be used as an effective molecular diagnostic tool for RP. PMID- 26155839 TI - Implementation and evaluation of an interprofessional simulation-based education program for undergraduate nursing students in operating room nursing education: a randomized controlled trial. AB - BACKGROUND: The present study was designed to implement an interprofessional simulation-based education program for nursing students and evaluate the influence of this program on nursing students' attitudes toward interprofessional education and knowledge about operating room nursing. METHODS: Nursing students were randomly assigned to either the interprofessional simulation-based education or traditional course group. A before-and-after study of nursing students' attitudes toward the program was conducted using the Readiness for Interprofessional Learning Scale. Responses to an open-ended question were categorized using thematic content analysis. Nursing students' knowledge about operating room nursing was measured. RESULTS: Nursing students from the interprofessional simulation-based education group showed statistically different responses to four of the nineteen questions in the Readiness for Interprofessional Learning Scale, reflecting a more positive attitude toward interprofessional learning. This was also supported by thematic content analysis of the open-ended responses. Furthermore, nursing students in the simulation based education group had a significant improvement in knowledge about operating room nursing. CONCLUSIONS: The integrated course with interprofessional education and simulation provided a positive impact on undergraduate nursing students' perceptions toward interprofessional learning and knowledge about operating room nursing. Our study demonstrated that this course may be a valuable elective option for undergraduate nursing students in operating room nursing education. PMID- 26155840 TI - Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis. AB - Most hepatocellular carcinoma (HCC) patients have complications, including cirrhosis and malnutrition. The efficacy of dietary supplementation with oral branched-chain amino acids (BCAAs) in HCC patients undergoing interventions has not been confirmed. Relevant publications on the efficacy and safety of oral BCAA supplementation for HCC patients undergoing anti-HCC interventions through September, 2014 were searched for identification in the PubMed, Embase, Web of Science, and the Cochrane Library databases. The pooled risk ratio (RR) and standardized mean difference (SMD) were used to assess the supplementation effects. A total of 11 eligible studies (974 patients in total) were evaluated and included in our analysis. Oral BCAA supplementation helped to maintain liver reserve with higher serum albumin (SMD = 0.234, 95% CI: 0.033-0.435, P = 0.022), and lower rates of ascites (RR = 0.545, 95% CI: 0.316-0.938, P = 0.029) and edema (RR = 0.494, 95% CI: 0.257-0.952, P = 0.035) than in the control group. BCAA supplementation seemed to be effective in improving mortality, especially in Child-Pugh class B patients, but the efficacy was not confirmed. Apparent effects were not found in improving HCC recurrence, total bilirubin, ALT, or AST. BCAA supplementation was relatively safe without serious adverse events. BCAA supplementation may be clinically applied in improving liver functional reserve for HCC patients and further improving the quality of life. PMID- 26155842 TI - Tubular overexpression of Gremlin in transgenic mice aggravates renal damage in diabetic nephropathy. AB - Diabetic nephropathy (DN) is currently a leading cause of end-stage renal failure worldwide. Gremlin was identified as a gene differentially expressed in mesangial cells exposed to high glucose and in experimental diabetic kidneys. We have described that Gremlin is highly expressed in biopsies from patients with diabetic nephropathy, predominantly in areas of tubulointerstitial fibrosis. In streptozotocin (STZ)-induced experimental diabetes, Gremlin deletion using Grem1 heterozygous knockout mice or by gene silencing, ameliorates renal damage. To study the in vivo role of Gremlin in renal damage, we developed a diabetic model induced by STZ in transgenic (TG) mice expressing human Gremlin in proximal tubular epithelial cells. The albuminuria/creatinuria ratio, determined at week 20 after treatment, was significantly increased in diabetic mice but with no significant differences between transgenic (TG/STZ) and wild-type mice (WT/STZ). To assess the level of renal damage, kidney tissue was analyzed by light microscopy (periodic acid-Schiff and Masson staining), electron microscopy, and quantitative PCR. TG/STZ mice had significantly greater thickening of the glomerular basement membrane, increased mesangial matrix, and podocytopenia vs. WT/STZ. At the tubulointerstitial level, TG/STZ showed increased cell infiltration and mild interstitial fibrosis. In addition, we observed a decreased expression of podocin and overexpression of monocyte chemoattractant protein-1 and fibrotic-related markers, including transforming growth factor-beta1, Col1a1, and alpha-smooth muscle actin. Together, these results show that TG mice overexpressing Gremlin in renal tubules develop greater glomerular and tubulointerstitial injury in response to diabetic-mediated damage and support the involvement of Gremlin in diabetic nephropathy. PMID- 26155841 TI - Community-based navigators for tobacco cessation treatment: a proof-of-concept pilot study among low-income smokers. AB - BACKGROUND: A majority of continuing smokers in the United States are socioeconomically disadvantaged (SED) adults, who are less likely than others to achieve and maintain abstinence despite comparable quit-attempt rates. A national research initiative seeks effective new strategies for increasing successful smoking cessation outcomes among SED populations. There is evidence that chronic and acute stressors may interfere with SED smokers who try to quit on their own. Patient navigators have been effectively used to improve adherence to chronic disease treatment. We designed and have pilot-tested an innovative, non-clinical community-based intervention--smoking cessation treatment navigators--to determine feasibility (acceptance, adherence, and uncontrolled results) for evaluation by randomized controlled trial (RCT). METHODS: The intervention was developed for smokers among parents and other household members of inner city pre school for low-income children. Smoking cessation treatment navigators were trained and deployed to help participants choose and adhere to evidence-based cessation treatment (EBCT). Navigators provided empathy, resource-linking, problem-solving, and motivational reinforcement. Measures included rates of study follow-up completion, EBCT utilization, navigation participation, perceived intervention quality, 7-day point abstinence and longest abstinence at three months. Both complete-case and intent-to-treat analyses were performed. RESULTS: Eighty-five percent of study participants (n = 40) completed final data collection. More than half (53%) enrolled in a telephone quitline and nearly three-fourths (71%) initiated nicotine replacement therapy. Participants completed a mean 3.4 navigation sessions (mean 30 min duration) and gave the intervention very high quality and satisfaction ratings. Self-reported abstinence was comparable to rates for evidence-based cessation strategies (21% among study completers, 18% using intent-to-treat analysis; median 21 days abstinent among relapsers). CONCLUSIONS: The pilot results suggest that smoking cessation treatment navigators are feasible to study in community settings and are well accepted for increasing use of EBCT among low-income smokers. Randomized controlled trial for efficacy is warranted. PMID- 26155843 TI - The cpk model of recessive PKD shows glutamine dependence associated with the production of the oncometabolite 2-hydroxyglutarate. AB - Since polycystic kidney disease (PKD) was first noted over 30 years ago to have neoplastic parallels, there has been a resurgent interest in elucidating neoplasia-relevant pathways in PKD. Taking a nontargeted metabolomics approach in the B6(Cg)-Cys1(cpk/)J (cpk) mouse model of recessive PKD, we have now characterized metabolic reprogramming in these tissues, leading to a glutamine dependent TCA cycle shunt toward total 2-hydroxyglutarate (2-HG) production in cpk compared with B6 wild-type kidney tissue. After confirmation of increased 2 HG expression in immortalized collecting duct cpk cells as well as in human autosomal recessive PKD tissue using targeted analysis, we show that the increase in 2-HG is likely due to glutamine-sourced alpha-ketoglutarate. In addition, cpk cells require exogenous glutamine for growth such that inhibition of glutaminase 1 decreases cell viability as well as proliferation. This study is a demonstration of the striking parallels between recessive PKD and cancer metabolism. Our data, once confirmed in other PKD models, suggest that future therapeutic approaches targeting this pathway, such as using glutaminase inhibitors, have the potential to open novel treatment options for renal cystic disease. PMID- 26155844 TI - Shedding of klotho by ADAMs in the kidney. AB - The anti-aging gene klotho plays an important role in Ca(2+) and phosphate homeostasis. Membrane-bound klotho is an essential coreceptor for fibroblast growth factor-23 and can be cleaved by proteases, including a disintegrin and metalloproteinase (ADAM)10 and ADAM17. Cleavage of klotho occurs at a site directly above the plasma membrane (alpha-cut) or between the KL1 and KL2 domain (beta-cut), resulting in soluble full-length klotho or KL1 and KL2 fragments, respectively. The aim of the present study was to gain insights into the mechanisms behind klotho cleavage processes in the kidney. Klotho shedding was demonstrated using a Madin-Darby canine kidney cell line stably expressing klotho and human embryonic kidney-293 cells transiently transfected with klotho. Here, we report klotho expression on both the basolateral and apical membrane, with a higher abundance of klotho at the apical membrane and in the apical media. mRNA expression of ADAM17 and klotho were enriched in mouse distal convoluted and connecting tubules. In vitro ADAM/matrix metalloproteinase inhibition by TNF484 resulted in a concentration-dependent inhibition of the alpha-cut, with a less specific effect on beta-cut shedding. In vivo TNF484 treatment in wild-type mice did not change urinary klotho levels. However, ADAM/matrix metalloproteinase inhibition did increase renal and duodenal mRNA expression of phosphate transporters, whereas serum phosphate levels were significantly decreased. In conclusion, our data show that renal cells preferentially secrete klotho to the apical side and suggest that ADAMs are responsible for alpha-cut cleavage. PMID- 26155845 TI - Sphingolipids, new kids on the block, promoting glomerular fibrosis in the diabetic kidney. PMID- 26155846 TI - The ugly duckling of urinary acidification: what is the contribution of the thick ascending limb of the loop of Henle to urinary acidification? PMID- 26155847 TI - Leukemia inhibitory factor attenuates renal fibrosis through Stat3-miR-29c. AB - Leukemia inhibitory factory (LIF), as a member of the IL-6 family, has been reported to ameliorate myocardial fibrosis and myocardial cell death. The purpose of the present study was to investigate the effect of LIF on renal fibrosis and its underlying mechanism. Our results showed, first, that LIF inhibited collagen type 1 and collagen type 3 expression induced by ANG II in NRK-49F (rat kidney fibroblast) cells and in mice with unilateral ureteral obstruction. Second, LIF induced Stat3 Tyr(705) phosphorylation and inhibited Stat3 Tyr(705) and Ser(727) phosphorylation induced by ANG II in NRK-49F cells. Third, LIF exerted an antirenal fibrosis effect mainly through activation of Stat3 Tyr(705) phosphorylation in NRK-49F cells. These effects of LIF were not observed in Stat3(-/-) cells. Finally, LIF-Stat3 upregulated microRNA-29c expression, and the latter downregulated collagen type 1 and collagen type 3 expression in NRK-49F cells and in mice with unilateral ureteral obstruction. In conclusion, LIF played a role in antirenal fibrosis by competitively activating Stat3 Tyr(705) phosphorylation, which upregulated microRNA-29c to suppress collagen expression. PMID- 26155848 TI - Time trends, improvements and national auditing of rectal cancer management over an 18-year period. AB - AIM: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. METHOD: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. RESULTS: During the study period, overall, relative and disease free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. CONCLUSION: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference. PMID- 26155849 TI - Epidemiology of candidaemia in a tertiary care university hospital: 10-year experience with 381 candidaemia episodes between 2001 and 2010. AB - Defining the epidemiology of and risk factors for candidaemia is necessary to guide empirical treatment. The objectives of this study were to determine the ranking of Candida among positive blood cultures, to define the epidemiology of candidaemia and to investigate patient characteristics and their relationship with C. albicans vs. non-albicans Candida (NAC) candidaemia. Candidaemia episodes between January 2001 and December 2010 were evaluated retrospectively. Patient characteristics were compared across Candida species. Candida ranked as the fifth most frequently isolated pathogen. Among 381 candidaemia episodes, 58.3% were due to C. albicans, followed by C. parapsilosis (15.2%), C. tropicalis (13.4%) and C. glabrata (6.8%). No statistically significant difference was observed in the distribution of C. albicans vs. NAC (P = 0.432). Patients with NAC had significantly higher rates of haematological disorders (P < 0.001) and neutropenia (P = 0.003), and were older (P = 0.024) than patients with C. albicans, whereas patients with urinary catheters had higher rates of C. albicans (P = 0.007). On species basis, C. tropicalis was more frequently isolated from patients with haematological disorders (P < 0.001) and neutropenia (P = 0.008). Patients with urinary catheters were less likely to have C. parapsilosis (P = 0.043). C. glabrata was most prevalent among patients with solid organ tumours (P = 0.038), but not evident in patients with haematological disorders. Local epidemiological features and risk factors may have important implications for the management of candidaemia. PMID- 26155850 TI - Isolated Septal Branch Myocardial Infarction Due to Coronary Spasm Mimicking Non Ischemic Late Gadolinium Enhancement Pattern on Cardiac Magnetic Resonance Imaging. PMID- 26155851 TI - Prognostic Significance of Neuroadrenergic Dysfunction for Cardiovascular Events in Patients With Acute Myocardial Infarction. AB - BACKGROUND: The dysregulation of systemic blood pressure (BP) variation or cardiac neuroadrenergic dysfunction is associated with adverse cardiovascular events. We aimed to clarify the prognostic significance of neuroadrenergic dysfunction for cardiovascular events in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: We enrolled 63 AMI patients (mean age, 67+/-12 years) underwent ambulatory BP monitoring (ABPM) and cardiac iodine (123)metaiodobenzylguanidine (MIBG) imaging within 4 weeks after AMI onset. We analyzed the circadian BP pattern and heart-to-mediastinum (H/M) MIBG uptake ratio. All the patients were followed for 2 years. The study endpoint was a composite of major adverse cardiovascular events, including all-cause death, MI, coronary revascularization except for the MI culprit lesion, and stroke. Patients with a non-dipper pattern (n=29) or an H/M ratio <1.96 (n=28) had a worse prognosis than those with either a dipper pattern (n=34) or an H/M ratio >=1.96 (n=35; log-rank, P=0.013 and 0.010, respectively). Patients with both a non dipper pattern and an H/M ratio <1.96 (n=12) had a significantly worse prognosis than did the other patients (P=0.0020). CONCLUSIONS: Dysregulation of BP variation and cardiac MIBG uptake were associated with cardiovascular events following AMI. Examining ABPM with MIBG imaging may potentially improve risk stratification in these patients. PMID- 26155852 TI - Aortic Dissection as a Possible Underlying Cause of Acute Ischemic Stroke. PMID- 26155853 TI - Inside Out, Outside in - Vasa Vasorum and Coronary Spasm. PMID- 26155854 TI - Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors. AB - Overexpression of ATAD2 (ATPase family, AAA domain containing 2) has been linked to disease severity and progression in a wide range of cancers, and is implicated in the regulation of several drivers of cancer growth. Little is known of the dependence of these effects upon the ATAD2 bromodomain, which has been categorized as among the least tractable of its class. The absence of any potent, selective inhibitors limits clear understanding of the therapeutic potential of the bromodomain. Here, we describe the discovery of a hit from a fragment-based targeted array. Optimization of this produced the first known micromolar inhibitors of the ATAD2 bromodomain. PMID- 26155855 TI - Zeolite membranes - a review and comparison with MOFs. AB - The latest developments in zeolite membranes are reviewed, with an emphasis on the synthesis techniques, including seed assembly and secondary growth methods. This review also discusses the current industrial applications of zeolite membranes, the feasibility of their use in membrane reactors and their hydrothermal stability. Finally, zeolite membranes are compared with metal organic framework (MOF) membranes and the latest advancements in MOF and mixed matrix membranes are highlighted. PMID- 26155856 TI - [Imaging and endoscopic diagnosis in Crohn's disease from art to science, and to practice]. PMID- 26155857 TI - [Contribution of computed tomography enterography (CTE) to the diagnosis, follow up and prognosis of Crohn's disease]. PMID- 26155858 TI - [Advances of magnetic resonance imaging in Crohn's disease]. PMID- 26155859 TI - [Significances and issues for capsule endoscopy in patients with Crohn's disease toward the appropriate use]. PMID- 26155860 TI - [Double-balloon endoscopy for diagnosis and management of Crohn's disease]. PMID- 26155861 TI - [Imaging and endoscopic diagnoses of the lesions of the small intestine in the management of Crohn's disease: discussion]. PMID- 26155862 TI - [Clinical examination of cases of radiation proctitis after intensity-modulated radiation therapy for prostate cancer]. AB - In our series of 366 patients who received intensity-modulated radiation therapy (IMRT) for prostate cancer, radiation proctitis developed in 24 patients. We examined the endoscopic evidence and clinical characteristics of radiation proctitis in these patients. The onset time was 2-29 months after treatment, with bloody bowel discharge being the most common symptom (22 cases). Colonoscopy revealed that the lesions tended to be concentrated on the rectal right anterior wall. Severity, according to the Tada classification, was 0b or Ia in 70.8% of all cases. The incidence of radiation proctitis decreased, and the clinical and endoscopic findings showed only mild radiation proctitis after IMRT. PMID- 26155863 TI - [Successful treatment of enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome and acute encephalopathy]. AB - We report a case of a woman in her twenties with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome who developed acute encephalopathy on day 5 of admission. She recovered after treatment with steroid pulse therapy, plasmapheresis, and recombinant thrombomodulin, without any adverse sequelae. We report this interesting case and provide a summary of the recent outbreak of enterohemorrhagic Escherichia coli O111. PMID- 26155864 TI - [A case of idiopathic portal vein obstruction identified by severe bleeding after a routine hemorrhoid operation]. AB - We report our experiences of a case of repeated bleeding after hemorrhoid ligation. A 53-year-old man underwent hemorrhoid ligation for internal hemorrhoids at another hospital. Postoperatively, he developed severe and repeated bleeding. Scanning revealed extrahepatic portal venous obstruction. The severe bleeding persisted after transfer to our institution, where we re-sutured the ligature and performed superior rectal artery embolism, leading to arrest of bleeding. The rectal varix arose due to portal hypertension, which resulted in the diagnosis of idiopathic extrahepatic portal vein obstruction. PMID- 26155865 TI - [A case of asymptomatic Sjogren's syndrome who developed interstitial pneumonia during monoclonal antibody therapy of Crohn's disease]. AB - A 67-year-old woman was diagnosed with ileocolic Crohn's disease at 61 years of age. Remission had been induced by the monoclonal antibody adalimumab, and maintenance therapy had continued since her diagnosis. However, she developed respiratory symptoms, including a dry cough. A chest CT scan revealed interstitial shadows in the lower pulmonary lobes. Although no sicca symptoms were noted, she was serologically positive for both anti-Sjogren's syndrome related antigen A and B antibodies, and salivary gland biopsy showed lymphocytic infiltration. Consequently, she was diagnosed as having asymptomatic Sjogren's syndrome. Infection or drug-induced pulmonary disease was considered unlikely, and the interstitial pneumonia was considered an extra-glandular presentation of Sjogren's syndrome. Thus, interstitial shadows, which appear during immunotherapy for Crohn's disease, could indicate asymptomatic Sjogren's syndrome; clinicians should consider this rare clinical picture when assessing such a patient. PMID- 26155866 TI - [Nonfunctioning pancreatic neuroendocrine tumor with extensive calcification]. AB - A 54-year-old woman exhibited pancreatic calcification on abdominal ultrasonography. Diagnostic imaging revealed a 20-mm mass with a 12-mm calcification in the tail of the pancreas. The mass was weakly enhanced in the early phase of contrast-enhanced CT. We performed pancreatectomy and splenectomy. Histopathological diagnosis was a nonfunctioning pancreatic neuroendocrine tumor (PNET), grade 2. This is a rare case of PNET with extensive calcification. PMID- 26155867 TI - [Occupational cholangiocarcinoma in a printer that responded to neoadjuvant chemoradiotherapy]. AB - A 42-year-old man working at a printing company was referred to our hospital for examination and treatment of icterus. We diagnosed resectable hilar cholangiocarcinoma and provided neoadjuvant chemoradiotherapy, extended right hepatectomy, and extrahepatic bile duct resection. A detailed history revealed that he had used 1,2-dichloropropane as part of his work as an offset colour proof-printer, and he has subsequently been recognized as having occupational cholangiocarcinoma. He has survived without recurrence for more than 2 and half years since the liver resection. In the present report, we describe our valuable experience of neoadjuvant chemoradiotherapy for occupational cholangiocarcinoma. PMID- 26155868 TI - [Mixed adenoneuroendocrine carcinoma of the gallbladder diagnosed by endoscopic transpapillary catheterization using bile cytology assessed by the cell block method]. AB - A 65-year-old woman was suspected of having advanced gallbladder cancer based on imaging results. This was considered inoperable because it was accompanied by possible liver metastasis. To confirm the diagnosis prior to chemotherapy, endoscopic transpapillary catheterization in the gallbladder (ETCG) was performed. The bile cytology was analyzed by the cell block method, which revealed mixed adenoneuroendocrine carcinoma. Based on the cytological results, extended cholecystectomy and partial hepatectomy were performed for the metastatic lesions. Bile cytology by ETCG with the cell block method was useful for deciding the therapeutic strategy in this patient with metastatic gallbladder cancer. PMID- 26155869 TI - [A case of mucinous cystic neoplasm of the liver]. AB - We present a case of resected mucinous cystic neoplasm of the liver in a 71-year old woman admitted to our hospital with epigastric discomfort. Abdominal ultrasonography and computed tomography revealed a multi-locular cystic tumor measuring 35 mm in diameter in segment IV of the liver. Left hepatic lobectomy was performed based on the diagnosis of mucinous cystic neoplasm of the liver; subsequent histology revealed that the tumor was multi-locular, cystic, and lined with a single layer of columnar epithelium with low-grade atypia and was associated with a typical ovarian-like stroma. There was no evidence (imaging or histological) to support communication of the cyst with the intrahepatic bile duct, despite modest bile deposition being observed in the cystic wall. The definitive diagnosis was mucinous cystic neoplasm with low-grade intrahepatic epithelial neoplasia. PMID- 26155870 TI - Upper Limb Strength and Muscle Volume in Healthy Middle-Aged Adults. AB - Our purpose was to characterize shoulder muscle volume and isometric moment, as well as their relationship, for healthy middle- aged adults. Muscle volume and maximum isometric joint moment were assessed for 6 functional muscle groups of the shoulder, elbow, and wrist in 10 middle-aged adults (46–60 y, 5M, 5F). Compared with young adults, shoulder abductors composed a smaller percentage of total muscle volume (P = .0009) and there was a reduction in shoulder adductor strength relative to elbow flexors (P = .012). We observed a consistent ordering of moment-generating capacity among functional groups across subjects. Although total muscle volume spanned a 2.3-fold range, muscle volume was distributed among functional groups in a consistent manner across subjects. On average, 72% of the variation in joint moment could be explained by the corresponding functional group muscle volume. These data are useful for improved modeling of upper limb musculoskeletal performance in middle-aged subjects, and may improve computational predictions of function for this group. PMID- 26155871 TI - Synthesis, in Vitro and in Silico Studies of Some Novel 5-Nitrofuran-2-yl Hydrazones as Antimicrobial and Antitubercular Agents. AB - In this study, we synthesized two series of novel 5-nitrofuran-2-carbohydrazides 21a-h and 22a-e in addition to a third series of thiophene-2-carbohydrazides 23a g to develop potent antimicrobial and/or antitubercular agents. The newly synthesized compounds were evaluated in vitro for their antimicrobial and antimycobacterial activities. Most of the 5-nitrofuran-2-carbohydrazides 21a-h and 22a-e displayed variable activity against Aspergillus fumigates, Staphylococcus aureus, Streptococcus pneumonia, Bacillis subtilis, Salmonella typhimurium, Klebsiella pneumonia, Escherichia coli and Mycobacterium tuberculosis. The sulfonamide derivative 21f exhibited superior potency and broad spectrum antimicrobial activity with minimum inhibitory concentration (MIC)=0.06 0.98 ug/mL and antimycobacterial activity with MIC=3.9 ug/mL. The 5-nitrofuran-2 carbohydrazides 21a, b, g, h and 22a-c exhibited significant antibacterial activity with MIC values in the range of 0.12-7.81 ug/mL. The significances of the 5-nitrofuran moiety and sulfonamide function were explored via the structure activity relationship (SAR) study. In addition, docking studies revealed that the p-amino benzoic acid (PABA) and binding pockets of the dihydropteroate synthase (DHPS) were successfully occupied by compound 21f. Furthermore, two quantitative structure-activity relationship (QSAR) models were built to explore the structural requirements which controlled the activity. PMID- 26155872 TI - Editorial: ChemSpider--a tool for Natural Products research. PMID- 26155873 TI - The effect of the MC4R gene on boar taint compounds, sexual maturity and behaviour in growing-finishing boars and gilts. AB - Societal pressure to ban surgical castration of male piglets is rising due to animal welfare concerns, thus other methods to prevent boar taint need to be explored. Genetic selection against boar taint appears to be a long-term sustainable alternative. However, as boar taint is linked to reproductive hormones, it is important to consider possible negative side effects such as delayed sexual maturity or changes in behaviour. We reported earlier that the melanocortin-4 receptor (MC4R) marker can be used to reduce boar taint levels in fat of boars. The objective of this study was to evaluate whether MC4R marker assisted selection for lower boar taint prevalence affects plasma levels of boar taint compounds and testosterone; sexual maturity; behaviour; skin lesions; and lameness in boars and gilts. Using an intervention study with a 2*2 design, 264 boars and gilts differing on position 893 of the MC4R gene (AA v. GG) were compared. The MC4R polymorphism did not affect the plasma concentration of either androstenone or testosterone at different time points, whereas the concentration of skatole was significantly lower (P=0.003) and the concentration of indole tended to be lower (P=0.074) in GG compared with AA boars. A higher percentage of gilts of the GG genotype were in puberty at slaughter age compared with AA gilts (P<0.001). The age of the boars at sexual maturity (as indicated by the first positive preputial smear test) did not differ between AA and GG boars. In contrast, weight of GG boars at sexual maturity tended to be lower (P=0.065). During the period from 6 weeks of age to slaughter, boars and gilts of the GG genotype showed more playing behaviour (P=0.015) and less passive and feeding behaviour (P=0.003). They showed more skin lesions on their back and caudal area (P=0.022), and tended to show more skin lesions on their head and anterior area (P=0.093) compared with AA animals. In conclusion, the polymorphism in the MC4R gene can be used as a marker without negative effects on reproduction characteristics in boars and gilts. Genetic selection towards a lower prevalence of boar taint will lead to more active pigs with more skin lesions. Management strategies may therefore be necessary to reduce skin lesions in the selected animals. PMID- 26155874 TI - In Vitro Transcription/Translation System: A Versatile Tool in the Search for Missing Proteins. AB - Approximately 18% of all human genes purported to encode proteins have not been directly evidenced at the protein level, according to the validation criteria established by neXtProt, and are considered to be "missing" proteins. One of the goals of the Chromosome-Centric Human Proteome Project (C-HPP) is to identify as many of these missing proteins as possible in human samples using mass spectrometry-based methods. To further this goal, a consortium of C-HPP teams (chromosomes 5, 10, 16, and 19) has joined forces to devise new strategies to identify missing proteins by use of a cell-free in vitro transcription/translation system (IVTT). The proposed strategy employs LC-MS/MS data-dependent acquisition (DDA) and targeted selective reaction monitoring (SRM) methods to scrutinize low-complexity samples derived from IVTT. The optimized assays are then applied to identify missing proteins in human cells and tissues. We describe the approach and show proof-of-concept results for development of LC SRM assays for identification of 18 missing proteins. We believe that the IVTT system, when coupled with downstream mass spectrometric identification, can be applied to identify proteins that have eluded more traditional methods of detection. PMID- 26155875 TI - Theoretical pharmacokinetic drug alterations in pediatric celiac disease. AB - INTRODUCTION: The incidence of pediatric celiac disease has risen and many of these children will receive medications at some time in their life. However, the absorption of drugs in pediatric patients with celiac disease has never been studied. The few studies that do exist have only been performed in adults and indicate that drug concentrations can be altered for some drugs. It is also noteworthy that few researchers have conducted studies to determine if the distribution, metabolism, and excretion of drugs are altered in celiac disease. AREAS COVERED: The pharmacokinetics of drugs greatly differ between children and adults. Combined with the pathophysiological changes known to occur with celiac disease, there is compelling evidence to support that drug exposure in pediatric celiac disease may be altered. Relevant characteristics of celiac disease that may affect drug disposition include intestinal atrophy, hypoalbuminemia, reduced CYP3A enzymes, and thyroid dysfunction. EXPERT OPINION: The safety and efficacy of drug dosing in children with celiac disease can be enhanced with additional pharmacokinetic studies of commonly prescribed drugs in this population. Ideally, these studies should include drugs that have high bioavailability, are highly protein bound, undergo extensive CYP3A enzyme metabolism, and/or have a narrow therapeutic range. PMID- 26155877 TI - Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome. AB - CONTEXT: Elaboration of oral liquid formulations is the best alternative when no marketed forms are available for pediatrics. OBJECTIVE: The development, characterization and stability evaluation of methadone (MI, MII, MIII) and phenobarbital (PI, PII) can be used for the treatment of neonatal abstinence syndrome (NAS). MATERIAL AND METHODS: A standard operating procedure was established and parameters such as appearance, pH, rheological behavior and drug content were evaluated at three temperatures for 90 days. RESULTS AND DISCUSSION: Changes in color of phenobarbital made necessary the storage below 25 degrees C. pH did not change in methadone solutions and was able to maintain phenobarbital solubilized. Degradation data at 4 degrees C fitted to Plateau equation followed by one phase decay. MI was stable for 60 days at the three temperatures; MII for 90 days at 4 and 25 degrees C and 60 days at 40 degrees C; MIII for 60 days at 4 degrees C, 15 days at 25 degrees C and 7 days at 4 degrees C. PI was stable for 60 days at 4 degrees C and 30 days at 25 degrees C. PII was stable for 7 days at 4 and 25 degrees C. All solutions met microbial specifications. CONCLUSION: A correct dosage for the treatment of NAS was guaranteed. PMID- 26155878 TI - Trials of Intervention Principles: Evaluation Methods for Evolving Behavioral Intervention Technologies. AB - In recent years, there has been increasing discussion of the limitations of traditional randomized controlled trial (RCT) methodologies for the evaluation of eHealth and mHealth interventions, and in particular, the requirement that these interventions be locked down during evaluation. Locking down these interventions locks in defects and eliminates the opportunities for quality improvement and adaptation to the changing technological environment, often leading to validation of tools that are outdated by the time that trial results are published. Furthermore, because behavioral intervention technologies change frequently during real-world deployment, even if a tested intervention were deployed in the real world, its shelf life would be limited. We argue that RCTs will have greater scientific and public health value if they focus on the evaluation of intervention principles (rather than a specific locked-down version of the intervention), allowing for ongoing quality improvement modifications to the behavioral intervention technology based on the core intervention principles, while continuously improving the functionality and maintaining technological currency. This paper is an initial proposal of a framework and methodology for the conduct of trials of intervention principles (TIPs) aimed at minimizing the risks of in-trial changes to intervention technologies and maximizing the potential for knowledge acquisition. The focus on evaluation of intervention principles using clinical and usage outcomes has the potential to provide more generalizable and durable information than trials focused on a single intervention technology. PMID- 26155879 TI - Cerebrovascular involvement and clinical presentation of late-life depression, findings from the NESDO study. AB - OBJECTIVES: The vascular depression hypothesis, which supposes a causal relation of vascular risk factors and vascular disease with depression, has not been definitively accepted. Inconsistent findings may be due to different clinical presentations of depression in older people with and without a clear history of stroke. We therefore aimed to investigate the association between vascular pathology, with and without previous stroke, and different symptom domains of depression. METHOD: For our study, we used baseline data of 378 people aged 60 years and older with a current depression who participated in the Netherlands Study of Depression in Older persons (NESDO), an observational (multicentre) cohort study. Using all information on vascular pathology and risk factors, three classes were operationalized: a first class of depressed older people with previous stroke; a second class of depressed older people with cardiovascular and peripheral arterial diseases, but without stroke; and a third class of depressed older people with no vascular disease. RESULTS: The depressed older people with previous stroke were characterized by more 'motivational' symptoms, which distinguished them from other depressed older people. Inclusion in this stroke group was also associated with having increased prevalence of hypertension, smoking more cigarettes, and lower alcohol consumption. CONCLUSIONS: Our findings suggest that the 'vascular depression' connotation should be reserved for depressed (older) patients with vascular pathology and evident cerebral involvement. PMID- 26155891 TI - High Sustained Virologic Response to Daclatasvir Plus Asunaprevir in Elderly and Cirrhotic Patients with Hepatitis C Virus Genotype 1b Without Baseline NS5A Polymorphisms. AB - INTRODUCTION: Oral daclatasvir (DCV; pangenotypic NS5A inhibitor) plus asunaprevir (ASV; NS3 protease inhibitor) is approved in Japan and Korea for treatment of chronic hepatitis C virus (HCV) genotype 1. Response to DCV + ASV is affected by DCV resistance-associated polymorphisms (RAPs) in HCV NS5A. The prevalence and influence of these RAPs on 12-week sustained virologic response (SVR12) to DCV + ASV was evaluated in Asian and non-Asian patients. METHODS: Data were pooled from 5 national and international studies of patients with HCV genotype 1b (GT-1b) receiving DCV + ASV at their recommended doses. Baseline NS5A RAPs and their effect on SVR12 were assessed overall, in older (>=65 years) patients, patients with cirrhosis, and in patients stratified by baseline HCV RNA or prior treatment experience with interferon-based therapy. RESULTS: Baseline NS5A sequences were available from 988 patients (374 Japanese; 125 Korean/Taiwanese; 489 from non-Asian countries), 979 of whom were assessed for SVR12. Pretreatment NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were present in 18% of Japanese and 12-13% of non-Japanese patients; these RAPs reduced SVR12 by 54.9% overall (93.9% [787/838] SVR12 when absent, 39.0% [55/141] SVR12 when present), with comparable reductions observed in Asians and non-Asians and across all categories of treatment experience, age, and cirrhosis. RAP-associated SVR12 rates declined with increasing baseline HCV RNA (SVR12 with RAPs: 64.7% [11/17] at 5-6 log10 IU/mL, 29.8% [14/47] at 7-8 log10). Without baseline RAPs, very high SVR12 rates (92-100%) were observed in older patients and patients with cirrhosis irrespective of national origin, with similarly high rates observed among treatment-naive and interferon-experienced patients and those with high baseline HCV RNA. CONCLUSIONS: Following DCV + ASV treatment, the SVR12 rates in GT-1b patients without baseline NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were very high (approximately 90-100%), irrespective of age, cirrhosis, prior interferon treatment, or baseline HCV RNA. FUNDING: Bristol-Myers Squibb. PMID- 26155892 TI - Effects of thiol antioxidants on the atropselective oxidation of 2,2',3,3',6,6' hexachlorobiphenyl (PCB 136) by rat liver microsomes. AB - Chiral polychlorinated biphenyl (PCB) congeners, such as PCB 136, are atropselectively metabolized to various hydroxylated PCB metabolites (HO-PCBs). The present study investigates the effect of two thiol antioxidants, glutathione and N-acetyl-cysteine (NAC), on profiles and chiral signatures of PCB 136 and its HO-PCB metabolites in rat liver microsomal incubations. Liver microsomes prepared from rats pretreated with phenobarbital were incubated with PCB 136 (5 MUM) in the presence of the respective antioxidant (0-10 mM), and levels and chiral signatures of PCB 136 and its HO-PCB metabolites were determined. Three metabolites, 5-136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol), 4-136 (2,2',3,3',6,6'-hexachlorobiphenyl-4-ol), and 4,5-136 (2,2',3,3',6,6' hexachlorobiphenyl-4,5-diol), were detected in all incubations, with 5-136 being the major metabolite. Compared to microsomal incubations without antioxidant, levels of 4,5-136 increased with increasing antioxidant concentration, whereas levels of PCB 136 and both mono-HO-PCBs were not affected by the presence of either antioxidant. PCB 136, 4-136, and 5-136 displayed significant atropisomeric enrichment; however, the direction and extent of the atropisomeric enrichment was not altered in the presence of an antioxidant. Because 4,5-136 can either be conjugated to a sulfate or glucuronide metabolite that is readily excreted or further oxidized a potentially toxic PCB 136 quinone, the effect of both thiol antioxidants on 4,5-136 formation suggests that disruptions of glutathione homeostasis may alter the balance between both metabolic pathways and, thus, PCB 136 toxicity in vivo. PMID- 26155893 TI - Decalmodulation of Cav1 channels by CaBPs. AB - Ca(2+)-dependent inactivation (CDI) is a negative feedback regulation of voltage gated Cav1 and Cav2 channels that is mediated by the Ca(2+) sensing protein, calmodulin (CaM), binding to the pore-forming Cav alpha1 subunit. David Yue and his colleagues made seminal contributions to our understanding of this process, as well as factors that regulate CDI. Important in this regard are members of a family of Ca(2+) binding proteins (CaBPs) that are related to calmodulin. CaBPs are expressed mainly in neural tissues and can antagonize CaM-dependent CDI for Cav1 L-type channels. This review will focus on the roles of CaBPs as Cav1 interacting proteins, and the significance of these interactions for vision, hearing, and neuronal Ca(2+) signaling events. PMID- 26155894 TI - Factors that may affect outcome in cervical artificial disc replacement: a systematic review. AB - PURPOSE: To identify the factors that may affect outcome in C-ADR and provide the pooled results of postoperative success rate of implanted segment range of motion (ROM), incidence of heterotopic ossification (HO), incidence of radiographic adjacent segment degeneration (r-ASD)/adjacent segment disease (ASD), and surgery rate for ASD. METHODS: We systematically searched in PubMed, Embase, Cochrane library and Web of knowledge from 2001 to May 2015. Two independent reviewers screened the primary records. Eleven questions regarding the effect of patient selection issues and radiographic parameters issues on outcome were posed previously. Studies addressing the framed questions were included for analysis. RESULTS: Twenty-two studies were included for the final analysis. Results showed that number of surgical level (single versus double-level) had no effect on primary clinical outcome and radiographic outcome, surgical level had no effect on clinical and radiographic outcome, and smoking habits had negative effect on clinical outcome. No evidence for the effect of patient's age and pathology category (radiculopathy or myelopathy) on outcome was found. The overall success rate of ROM was 79.4%. ROM of the implanted segment and cervical sagittal alignment had no effects on clinical outcome. The pooled incidences of grade 1-4 HO and grade 3-4 HO were 27.7 and 7.8%, respectively. The pooled incidence of r ASD and surgery rate for ASD were 42.4 and 3.8%, respectively. CONCLUSIONS: The available evidence showed that most of the pre-selected factors had no effect on outcome after C-ADR, and the ROM success rate, incidence of HO and r-ASD/ASD, and surgery rate for ASD are acceptable. There is a lack of evidence from RCTs for some factors. PMID- 26155895 TI - Predictors of inpatient morbidity and mortality in adult spinal deformity surgery. AB - PURPOSE: This nationwide study identifies ASD surgical risk factors for morbidity/mortality. METHODS: NIS discharges from 2001 to 2010 aged 25+ with scoliosis diagnoses, 4+ levels fused, and procedural codes for anterior and/or posterior thoracic and/or lumbar spinal fusion and refusion were included. Demographics, comorbidities and procedure-related complications were determined for each subgroup (degenerative, congenital, idiopathic, other). Multivariate analysis reported as [OR (95% CI)]. RESULTS: 11,982 discharges were identified. Morbidity, excluding device-related, and mortality rates were 50.81 and 0.28%, respectively. Certain comorbidities were associated with increased morbidity/mortality: congestive heart failure (CHF) [1.62 (1.42-1.84)] [5.67 (3.30-9.73)], coagulopathy [3.52 (3.22-3.85)] [2.32 (1.44-3.76)], electrolyte imbalance [2.65 (2.52-2.79)] [4.63 (3.15-6.81)], pulmonary circulation disorders [9.45 (7.45-11.99)] [8.94 (4.43-18.03)], renal failure [1.29 (1.13-1.47)] [5.51 (2.57-11.82)], and pathologic weight loss [2.38 (2.01-2.81)] [7.28 (4.36-12.14)]. Chronic pulmonary disease was associated with higher morbidity [1.08 (1.02 1.14)]; liver disease was linked to increased mortality [36.09 (16.16-80.59)]. 9+ level fusions had increased morbidity vs 4-8 level fusions [1.69 (1.61-1.78)] and refusions [1.08 (1.02-1.14)]. Idiopathic scoliosis was associated with decreased morbidity vs all other subgroups [0.85 (0.80-0.91)]. Age >65 was associated with increased morbidity and mortality vs 25-64 group [1.09 (1.05-1.14)] [3.49 (2.31 5.29)]. Females had increased morbidity [1.18 (1.13-1.23)] and decreased mortality [0.30 (0.21-0.44)]. Mean comorbidity index (0.55) and age (64.38) for degenerative cohort were higher vs all other subgroups (P < 0.0001). CONCLUSIONS: Longer fusions were associated with increased morbidity. Age >65 was associated with increased morbidity/mortality, while females were associated with increased morbidity but decreased mortality. Idiopathic scoliosis had decreased morbidity. Degenerative ASD cases had higher comorbidity indices, potentially due to older age. This study is clinically useful for patient education, surgical decision making, and optimizing patient outcomes. PMID- 26155896 TI - An inflammatory pseudotumor in the thoracic epidural space presenting with progressive paraplegia: a histopathological diagnosis with clinical and radiological uncertainty. Case report with literature review. AB - INTRODUCTION: Inflammatory pseudotumors (IPTs) are benign lesions with unknown etiology, probably an immunological reaction to a traumatic or an infective insult or sometimes considered as an IgG4-related autoimmune disorder. It can occur as an isolated or multi-centric lesion and are reported to involve almost all parts of the human body. Although lung and orbital IPTs are reported commonly, central nervous system involvement is a rare occurrence. Only seven cases of spinal epidural IPTs have been reported to date. These are clinically and radiologically a diagnosis of exclusion. It is an exclusive histopathological diagnosis. CASE REPORT: We present here a 49-year-old female with 2 months history of progressive weakness in lower limbs, with no history suggestive of any traumatic, infective, inflammatory, or neoplastic pathology. Both clinical and radiological investigations were inconclusive. There was a mass lesion in the epidural space (predominantly in the posterior and right lateral space) at T1-T3 vertebral levels compressing the thoracic spinal cord. Considering the progressive nature of her neurological deficit, an emergency decompressive laminectomies of T1-T3 vertebrae were done with excision of the compressive mass lesion. Histopathological examination showed a rich lympho-plasmacytic cell infiltrates with storiform spindle cells and dense fibrosis, which was diagnostic of IPT. Post-operatively there was a rapid recovery in neurology and she became ambulatory at the end of 2 weeks. The purpose of this case report is to discuss the clinical, histopathological and radiological features, differential diagnosis, management, and prognosis of spinal IPT on the background of relevant literature review. PMID- 26155897 TI - Surgical correction of scoliosis in patients with severe cerebral palsy. AB - INTRODUCTION: There is a lack of data in the literature on surgical correction of severe neuromuscular scoliosis in patients with serious extent of cerebral palsy. The purpose of this retrospective cohort study was to analyze the radiological and clinical results after posterior-only instrumentation (group P) and combined anterior-posterior instrumentation (group AP) in severe scoliosis in patients with Gross Motor Function Classification System grades IV and V. MATERIALS AND METHODS: All eligible patients who underwent surgery in one institution between 1997 and 2012 were analyzed, and charts, surgical reports, and radiographs were evaluated with a minimum follow-up period of 2 years. RESULTS: Fifty-seven patients were included (35 in group P, 22 in group AP), with a median follow-up period of 4.1 years. The preoperative mean Cobb angles were 84 degrees (34 % flexibility) in group P and 109 degrees (27 % flexibility) in group AP. In group P, the Cobb angle was 39 degrees (54 % correction) at discharge and 43 degrees at the final follow-up, while in group AP the figures were 54 degrees (50 % correction) at discharge and 56 degrees at the final follow-up. Major complications occurred in 23 vs. 46 % of the patients, respectively. Preoperative curve flexibility was an important predictor for relative curve correction, independently of the type of surgery. CONCLUSION: Posterior-only surgery appears to lead to comparable radiological results, with shorter operating times and shorter intensive-care unit and hospital stays than combined surgery. The duration of surgery was a relevant predictor for complications. PMID- 26155898 TI - Predictors of surgical outcome in cervical spondylotic myelopathy: focusing on the quantitative signal intensity. AB - PURPOSE: The association between intramedullary increased signal intensity (ISI) on T2-weighted magnetic resonance imaging and surgical outcome in cervical spondylotic myelopathy (CSM) remains controversial. The purpose of this study is to assess the impact of quantitative signal change ratio (SCR) on the surgical outcome for CSM. METHODS: The prospective study included 108 consecutive patients who underwent surgical treatment for CSM. The Japanese Orthopaedic Association (JOA) score and recovery rate were used to evaluate clinical outcomes. JOA recovery rate less than 50% was defined as a poor clinical result. The SCR was defined as the signal intensity at the level of ISI or severely compressed cord (in cases with no ISI) divided by the signal intensity at the C7-T1 disc level. Age, sex, body mass index, duration of symptoms, surgical technique, preoperative JOA score, levels of compression, preoperative SCR, preoperative C2-7 angle, preoperative C2-7 range of motion were assessed. RESULTS: Forty patients (37.0%) had a recovery rate of less than 50%. Multivariate logistic regression analysis revealed that a higher preoperative SCR and a longer duration of symptoms were significant risk factors for a poor clinical outcome. Receiver operating characteristic (ROC) curve analysis showed that the optimal preoperative SCR cutoff value as a predictor of poor clinical result was 1.46. The area under the ROC curve of preoperative SCR for predicting a poor surgical outcome was 0.844. CONCLUSIONS: Preoperative SCR significantly reflected the surgical outcome in patients with CSM. Patients with SCR greater than or equal to 1.46 can experience poor recovery after surgery. PMID- 26155899 TI - What can patients do to facilitate shared decision making? A qualitative study of patients with depression or schizophrenia and psychiatrists. AB - PURPOSE: Patient involvement in decision making is endorsed by patients and professionals. While research has recently been conducted on how professionals can promote shared decision making (SDM), little is known about how patients can also facilitate SDM. METHODS: Seven focus groups were conducted: 3 with psychiatrists and 4 with patients with schizophrenia or depression. The focus groups were transcribed and independently coded line by line by 2 researchers. Data were analyzed using content analysis. RESULTS: Seven themes related to patient attitudes and behaviors were identified: honesty and openness with one's psychiatrist and oneself, trust in one's psychiatrist and patience with the treatment, respect and politeness, informing the psychiatrist and giving feedback, engagement/active participation during the consultation, gathering information/preparing for the consultation and implementing decisions. Barriers (e.g., avolition, lack of decisional capacity, powerlessness during involuntary treatment) and facilitators of active patient behavior were also identified. CONCLUSIONS: There are various ways in which patients can facilitate SDM/play a more active role in decision making, with patients emphasizing being open and honest and psychiatrists emphasizing being active in the consultation. Interventions to increase active patient behavior may enhance SDM in mental health care. PMID- 26155900 TI - Epidemiology and burden of bipolar disorder in Africa: a systematic review of data from Africa. AB - BACKGROUND: Bipolar disorder impacts negatively on the patient, the family, as well as the society. It taxes the health care services due to a combination of the illness with associated medical and psychiatric comorbidities. In Africa, unfortunately, knowledge of the epidemiology and burden of bipolar disorder is based mainly on studies from the USA and Europe. In this systematic review of literature from Africa, we highlight the epidemiology and burden of bipolar disorder. METHODS: A systematic review of publications from Africa relating to the epidemiology and burden of bipolar disorder was conducted. RESULT: Data from community surveys conducted in Nigeria and Ethiopia indicated a lifetime prevalence estimate of 0.1 % to 1.83 for bipolar disorder. Missed diagnosis rate of bipolar disorder was up to 36.2 %. In one study, 8.1 % of the males and 5.4 % of the females reported a previous suicide attempt. A study showed that up to 60 % of patients with bipolar disorder had at least one comorbidity. There were no reports on all-cause mortality and cost of illness. CONCLUSION: Bipolar disorder is a major mental health problem in Africa. Scientific findings on bipolar disorder from Africa are consistent with the existing literature from other parts of the world. There still exists a dearth of high quality studies addressing the epidemiological, clinical, social, and economic burden of the disorder. PMID- 26155902 TI - Identification of lncRNA MEG3 Binding Protein Using MS2-Tagged RNA Affinity Purification and Mass Spectrometry. AB - Long noncoding RNAs (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides. Recently in mammals, thousands of long noncoding RNAs have been identified and studied as key molecular players in different biological processes with protein complexes. As a long noncoding RNA, maternally expressed gene 3 (MEG3) plays an important role in many cellular processes. However, the mechanism underlying MEG3 regulatory effects remains enigmatic. By using the specific interaction between MS2 coat protein and MS2 RNA hairpin, we developed a method (MS2-tagged RNA affinity purification and mass spectrometry (MTRAP-MS)) to identify proteins that interact with MEG3. Mass spectrometry and gene ontology (GO) analysis showed that MEG3 binding proteins possess nucleotide binding properties and take part in transport, translation, and other biological processes. In addition, interleukin enhancer binding factor 3 (ILF3) and poly(A) binding protein, cytoplasmic 3 (PABPC3) were validated for their interaction with MEG3. These findings indicate that the newly developed method can effectively enrich lncRNA binding proteins and provides a strong basis for studying MEG3 functions. PMID- 26155901 TI - Duration of unspecific prodromal and clinical high risk states, and early help seeking in first-admission psychosis patients. AB - PURPOSE: Prevention of psychosis requires both presence of clinical high risk (CHR) criteria and early help-seeking. Previous retrospective studies of the duration of untreated illness (i.e. prodrome plus psychosis) did not distinguish between prodromal states with and without CHR symptoms. Therefore, we examined the occurrence of CHR symptoms and first help-seeking, thereby considering effects of age at illness-onset. METHODS: Adult patients first admitted for psychosis (n = 126) were retrospectively assessed for early course of illness and characteristics of first help-seeking. RESULTS: One-hundred and nine patients reported a prodrome, 58 with CHR symptoms. In patients with an early illness onset before age 18 (n = 45), duration of both illness and psychosis were elongated, and CHR symptoms more frequent (68.9 vs. 33.3 %) compared to those with adult illness-onset. Only 29 patients reported help-seeking in the prodrome; this was mainly self-initiated, especially in patients with an early illness onset. After the onset of first psychotic symptoms, help-seeking was mainly initiated by others. State- and age-independently, mental health professionals were the main first point-of-call (54.0 %). CONCLUSIONS: Adult first-admission psychosis patients with an early, insidious onset of symptoms before age 18 were more likely to recall CHR symptoms as part of their prodrome. According to current psychosis-risk criteria, these CHR symptoms, in principle, would have allowed the early detection of psychosis. Furthermore, compared to patients with an adult illness-onset, patients with an early illness-onset were also more likely to seek help on their own account. Thus, future awareness strategies to improve CHR detection might be primarily related to young persons and self perceived subtle symptoms. PMID- 26155903 TI - Stroke in HIV-infected African Americans: a retrospective cohort study. AB - The risk of having a first stroke is nearly twice as high among African Americans compared to Caucasians. HIV/AIDS is an independent risk factor for stroke. Our study aimed to report the risk factors and short-term clinical outcomes of African Americans with HIV infection and new-onset stroke admitted at the Johns Hopkins Hospitals (2000-2012). Multivariate linear regression was used to examine the association between potential predictors and odds of an unfavorable outcome, defined as a higher modified Rankin Scale (mRS) score on hospital discharge. African Americans comprised 105/125 (84%) of HIV-infected new-onset stroke inpatients (median age 50 years; 69% men; median CD4 140/mL; ischemic 77%; 39% taking highly active antiretroviral therapy). Vascular risk factors were common: hypertension (67%), cigarette smoking (66%), dyslipidemia (42%), hepatitis C (48%), intravenous drug abuse (32%), and prior myocardial infarction (29%). Prior aspirin and statin use were uncommon (18%, 9%). Unfavorable outcome (mRS score 4 6, n = 22 of 90 available records) was noted in 24% of patients, including seven in-hospital deaths. On multivariate analyses, higher CD4 count on hospital admission was associated with a lower mRS (-0.2 mRS points per 1 unit increase in CD4, 95% CI (-0.3, 0), p = 0.03). Intracerebral hemorrhage was also associated with a lower mRS (1.0 points lower, 95% CI (0.2, 1.8) compared to ischemic stroke, p = 0.01) after adjustment for other potential predictors. This underscores the importance of HIV infection on functional stroke outcomes beyond its recognized influence on stroke risk. PMID- 26155904 TI - Effect of low-level laser therapy on lung injury induced by hindlimb ischemia/reperfusion in rats. AB - To investigate the effect of low-level laser therapy (LLLT 650 nm) on the lung remote organ injury induced by hindlimb ischemia/reperfusion (I/R). The experiments were performed on 50 healthy mature male Wistar rats weighing mean 230 +/- 20 g. The rats were randomly allocated into five equal groups as follows: normal group (animals nonmanipulated), sham group (operated with no ischemia), laser group (animals nonmanipulated and irradiated with laser), I/R group, and I/R + LLLT group. Rats were prepared for sterile surgery, and then, right hindlimbs were subjected to I/R induced by the femoral artery occlusion for duration of 120 min, followed by a 60-min reperfusion. The LLLT (K30 handheld probe, AZOR, Technica, Russia, 650 nm, 30 mW, surface area = 1 cm(2), 60 S/cm(2), energy density = 1.8 J/cm(2)) was carried out by irradiating the rats over a unique point on the skin over the right upper bronchus for 5 and 15 min after initiating reperfusion for 3 min. At the end of the trial, rats were euthanized under deep anesthesia and the right lung tissues were removed. Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and nitric oxide (NO), malondialdehyde (MDA), and glutathione (GSH) levels were measured in the lung tissues. The tissue samples were further examined histopathologically under light microscopy. It was found that I/R elevated MPO activity, MDA, and NO levels accompanied by a reduction in SOD activities and GSH levels (P < 0.05). LLLT restored MDA and NO levels, MPO and SOD activity, GSH levels, and lung injury scores (P < 0.05). In light of these findings, the LLLT has alleviated the lung tissue injuries after skeletal muscle I/R in this experimental model. PMID- 26155905 TI - A new direction in psychology and health: Resistance exercise training for obese children and adolescents. PMID- 26155906 TI - Absorption and plasma kinetics of collagen tripeptide after peroral or intraperitoneal administration in rats. AB - Collagen tripeptide (CTP) is a collagen-derived compound containing a high concentration of tripeptides with a Gly-X-Y sequence. In this study, the concentrations and metabolites of CTP were monitored in rat plasma after its administration. We performed a quantitative analysis using high-performance liquid chromatography tandem mass spectrometry according to the isotopic dilution method with stable isotopes. We confirmed that the tripeptides Gly-Pro-Hyp, Gly Pro-Ala, and Gly-Ala-Hyp were transported into the plasma. Dipeptides, which are generated by degradation of the N- or C-terminus of the tripeptides Gly-Pro-Hyp, Gly-Pro-Ala, and Gly-Ala-Hyp, were also present in plasma. The plasma kinetics for peroral and intraperitoneal administration was similar. In addition, tripeptides and dipeptides were detected in no-administration rat blood. The pharmacokinetics were monitored in rats perorally administered with Gly-[(3)H]Pro Hyp. Furthermore, CTP was incorporated into tissues including skin, bone, and joint tissue. Thus, administering collagen as tripeptides enables efficient absorption of tripeptides and dipeptides. PMID- 26155908 TI - Drosophila melanogaster mitochondrial Hsp22: a role in resistance to oxidative stress, aging and the mitochondrial unfolding protein response. AB - Aging is characterized by the accumulation of dysfunctional mitochondria. Since these organelles are involved in many important cellular processes, different mechanisms exist to maintain their integrity. Among them is the mitochondrial unfolding protein response, which triggers the expression of a set of proteins aimed at re-establishing mitochondrial homeostasis. The induction of mitochondrial chaperones expression, particularly of Hsp60 and Hsp70, is a hallmark of this pathway. In Drosophila melanogaster, Hsp22 is also up-regulated by mitochondrial stress. This small heat shock protein is one of the members of the family to be localized inside mitochondria. One characteristic of Drosophila Hsp22 is its preferential up-regulation during aging and in oxidative stress conditions. It is a beneficial protein since its over-expression increases lifespan and resistance to stress while its down-regulation is detrimental. This review focuses on Drosophila Hsp22 and its links with the mitochondrial unfolding protein response and the aging process, in addition to highlight the important role of this sHSP in mitochondrial homeostasis. PMID- 26155909 TI - Letter to the editor. PMID- 26155907 TI - T-wave axis deviation is associated with biomarkers of low-grade inflammation. Findings from the MOLI-SANI study. AB - T-wave axis deviation (TDev) may help identifying subjects at risk for major cardiac events and mortality, but the pathogenesis of TDev is not well established; in particular, the possible association between TDev and inflammation is unexplored and unknown. We aimed at investigating the association between low-grade inflammation and TDev abnormalities by conducting a cross sectional analysis on 17,507 subjects apparently free from coronary heart and haematological diseases enrolled in the MOLI-SANI study. TDev was measured from a standard 12-lead resting electrocardiogram. High sensitivity (Hs) C-reactive protein (CRP), leukocyte (WBC) and platelet counts, neutrophil or granulocyte to lymphocyte ratios were used as markers of inflammation. In multivariable model subjects reporting high CRP levels had higher odds of having borderline and abnormal TDev (OR=1.70; 95 %CI: 1.53-1.90 and OR=1.72; 95 %CI: 1.23-2.41, respectively); the association was still significant, although reduced, after controlling for body mass index (OR=1.17; 95 %CI: 1.05-1.32, for borderline and OR=1.46; 95 %CI: 1.03-2.08, for abnormal). Similarly, higher neutrophil or granulocyte to lymphocyte ratios were associated with increased odds of having abnormal TDev. Neither platelet nor leukocyte counts were associated with abnormal TDev. The relationship between CRP with TDev abnormalities was significantly stronger in men, in non- obese or normotensive individuals, and in those without metabolic syndrome. In conclusion, C-reactive protein and some cellular biomarkers of inflammation such as granulocyte or neutrophil to lymphocyte ratios were independently associated with abnormal TDev, especially in subjects at low CVD risk. These results suggest that a low-grade inflammation likely contributes to the pathogenesis of T- wave axis deviation. PMID- 26155910 TI - Successful intraperitoneal rituximab treatment in a patient with therapy resistant malignant ascites due to mantle cell lymphoma. PMID- 26155911 TI - VLA-4 and CXCR4 expression levels show contrasting prognostic impact (favorable and unfavorable, respectively) in acute myeloid leukemia. AB - Very late antigen-4 (VLA-4) and CXC chemokine receptor 4 (CXCR4) perform critical roles in the adhesion of hematopoietic and leukemic stem cells to marrow stromal cells. This mechanism is associated with chemoresistance in patients with acute myeloid leukemia (AML). Here, we measured VLA-4 and CXCR4 expressions in leukemic myeloblasts to determine their prognostic implications. Using multicolor flow cytometry, positive VLA-4 and CXCR4 expressions were measured in leukemic myeloblasts in bone marrow aspirates that were obtained from newly diagnosed adult AML patients (n = 98). VLA-4 expression was higher in patients at favorable or intermediate cytogenetic risk than in patients at poor risk (p < 0.001 and p = 0.002, respectively), but CXCR4 expression was not significantly different. Among the 72 non-promyelocytic leukemia patients analyzed who received cytarabine + anthracycline-based induction chemotherapy, high VLA-4 expression was independently associated with a high probability of complete remission (p = 0.019) and superior relapse-free survival (RFS) (p < 0.001). However, high CXCR4 expression independently increased the probability of relapse (p = 0.002) and was associated with a shorter RFS (p = 0.006). When categorizing patients into three groups according to VLA-4 and CXCR4 expression levels, the group of high VLA-4 and low CXCR4 showed longer RFS (p = 0.001) and overall survival (OS) (p = 0.011) than the group of low VLA-4 or high CXCR4. PMID- 26155913 TI - Does everything a surgeon takes out have to be seen by a pathologist? A review of the current pathology practice. AB - Histopathologic examination of surgically removed tissues and organs is an important aspect of modern hospital quality health care. Most surgical specimens deserve to be submitted for pathologic examination, which may yield valuable new information relevant for the future treatment of the patient. A small number of specimens, recognized as providing limited or no valuable clinical data during pathologic examination, may be placed on the list of specimens "exempt from submission" or those that are labeled as "for gross examination only." Guidelines written by the committees of the national regulatory organizations provide general orientation on how to deal with various specimens, but the final decision on which type of specimen to eliminate and which ones to include for pathologic examination rests on local governing and advisory bodies of each institution. Particular lists of specimens exempt from pathologic examination are best generated through a consensus agreement of clinical and laboratory physicians. Even though there is general nationwide and even international consensus on which types of specimens deserve pathologic examination and which do not, there are still discussions about the necessity of some pathologic examinations. PMID- 26155915 TI - Three-dimensional macro-scale assessment of regional and temporal wall shear stress characteristics on aortic valve leaflets. AB - The aortic valve (AV) achieves unidirectional blood flow between the left ventricle and the aorta. Although hemodynamic stresses have been shown to regulate valvular biology, the native wall shear stress (WSS) experienced by AV leaflets remains largely unknown. The objective of this study was to quantify computationally the macro-scale leaflet WSS environment using fluid-structure interaction modeling. An arbitrary Lagrangian-Eulerian approach was implemented to predict valvular flow and leaflet dynamics in a three-dimensional AV geometry subjected to physiologic transvalvular pressure. Local WSS characteristics were quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI) and temporal shear gradient (TSG). The dominant radial WSS predicted on the leaflets exhibited high amplitude and unidirectionality on the ventricularis (TSM>7.50 dyn/cm(2), OSI < 0.17, TSG>325.54 dyn/cm(2) s) but low amplitude and bidirectionality on the fibrosa (TSM < 2.73 dyn/cm(2), OSI>0.38, TSG < 191.17 dyn/cm(2) s). The radial WSS component computed in the leaflet base, belly and tip demonstrated strong regional variability (ventricularis TSM: 7.50-22.32 dyn/cm(2), fibrosa TSM: 1.26-2.73 dyn/cm(2)). While the circumferential WSS exhibited similar spatially dependent magnitude (ventricularis TSM: 1.41-3.40 dyn/cm(2), fibrosa TSM: 0.42-0.76 dyn/cm(2)) and side-specific amplitude (ventricularis TSG: 101.73-184.43 dyn/cm(2) s, fibrosa TSG: 41.92-54.10 dyn/cm(2) s), its temporal variations were consistently bidirectional (OSI>0.25). This study provides new insights into the role played by leaflet-blood flow interactions in valvular function and critical hemodynamic stress data for the assessment of the hemodynamic theory of AV disease. PMID- 26155914 TI - Dysregulation of the Rb pathway in recurrent pleomorphic adenoma of the salivary glands. AB - Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and while mostly benign, recurrences (RPA) and malignant transformation to carcinoma ex-PA (CXPA) do occur. Cell cycle proteins important in its tumorigenesis have been studied as markers for PA with a high risk of RPA or CXPA. The aim of the present study was to investigate cell cycle markers p-16, cyclin D1, CDK4, E2F, and retinoblastoma (Rb) in this context. Expression of p16, cyclin D1, E2F, CDK4, and Rb was studied by immunohistochemistry in 24 cases of PA, 21 of RPA, and 2 of CXPA. The presence of HPV was assessed by in situ hybridization. Immunostaining for p16 and cyclin D1 was negative or weakly positive in most cases of PA while strongly positive in the majority of RPA and both CXPA cases. Staining for Rb and CDK4 was either negative or weakly positive in PA, RPA, and CXPA. Expression of E2F was stronger in RPA and CXPA than in PA. Nuclear reactivity for HPV was not observed in any case. In conclusion, the strong staining for p16, cyclinD1, and E2F in RPA and CXPA, while weak or negative in PA, suggests that these proteins might be involved in recurrence and malignant transformation of PA. PMID- 26155917 TI - Mammalian ranges are experiencing erosion of natural darkness. AB - The continuous increase in the intensity and extent of anthropogenic artificial light has significantly shaped Earth's nighttime environment. This environmental change has effects across the natural world, with consequences for organismal physiology and behaviour and the abundances and distributions of species. Here, we evaluate for the first time the relations between the spatio-temporal patterns of anthropogenic nighttime light and the distribution of terrestrial mammals, one of the most endangered species groups and one that expresses varying time partitioning strategies. Using descriptive statistics, trend tests and spatial prioritization analysis we show that in most places on earth there is a terrestrial mammal species whose range is experiencing detectable artificial light. For most species this tends only to be for small parts of their range, and those affected across large parts are typically rare. Over time (1992-2012), an increase in mean light intensity was found for the ranges of the majority of species, with very few experiencing a decrease. Moreover, nocturnal species are more likely to experience an increase in light within their ranges. This is of conservation concern as many terrestrial mammals are nocturnal and therefore often particularly vulnerable to a pressure such as artificial light at night. PMID- 26155916 TI - The effect of imipramine, ketamine, and zinc in the mouse model of depression. AB - Relationship between the chronic and excessive exposure to glucocorticoids and the development of psychiatric disorders, including depression, has been described in the literature. We decided to investigate whether a combination of agents with antidepressant activity (i.e., imipramine, ketamine, and Zn(2+)) may influence/reverse the depressogenic effect of dexamethasone therapy. The antidepressant-like effect was assessed by the forced swim test in adult mice. The inhibitory activity of dexamethasone was dose-dependent: only the highest tested dose of the glucocorticoid (i.e., 64 MUg/kg) given as a single injection increased immobility time, whereas 16 MUg/kg/day of dexamethasone administered repeatedly (for 14 days) induced a significant alteration in animal behavior. Both the acute or sub-chronic administration of the active doses of imipramine (10 mg/kg), Zn(2+) (30 mg/kg), and ketamine (30 mg/kg), and the combinations of their per se inactive doses reversed the inhibitory activity of dexamethasone (16 MUg/kg/day) administered for 14 consecutive days. Whereas a single injection of an inhibitory dose of dexamethasone (64 MUg/kg) was not able to abolish the antidepressant effect of imipramine (5 mg/kg), Zn(2+) (10 mg/kg), and imipramine Zn(2+) combination (2.5 and 5 mg/kg, respectively) given once a day for 14 consecutive days. Our findings indicate that the chronic dexamethasone injection procedure has some potential as an animal model of depression and they further support the theory of interplay between glutamatergic neurotransmission and the chronic or excessive exposition to glucocorticoids. PMID- 26155918 TI - Ten-year weight gain in smokers who quit, smokers who continued smoking and never smokers in the United States, NHANES 2003-2012. AB - BACKGROUND/OBJECTIVES: Weight gain after quitting smoking is a common concern for smokers and can discourage quit attempts. The purpose of this analysis was to describe the long-term weight gain, smoking cessation attributable (SCA) weight gain and describe their relationship to cigarette consumption and body mass index (BMI) 10 years ago in a contemporary, nationally representative sample of smokers who continued to smoke and those who quit. SUBJECTS/METHODS: In all, 12,204 adults ?36 years old were selected from the 2003-2012 National Health and Nutrition Examination Survey (NHANES). Ten-year weight gain for never, continuing and former smokers (who quit 1-10 years ago) was calculated by body mass index (BMI) 10 years ago and cigarettes per day (CPD). SCA weight gain was calculated by taking the difference between the adjusted mean 10-year weight gain of former smokers and that of continuing smokers. RESULTS: Mean 10-year weight gain among continuing smokers was 3.5 versus 8.4 kg among former smokers; the SCA weight gain was 4.9 kg. After Bonferroni correction, there was no significant difference in overall weight gain between continuing and former smokers of 1-14 CPD, and SCA weight gain was lowest in this group (2.0 kg, confidence interval (CI): 0.3, 3.7). SCA weight gain was highest for former smokers of ?25 CPD (10.3 kg, CI: 7.4, 13.2) and for those who were obese (7.1 kg, CI: 2.9, 11.3) mostly because of lower than average weight gain or weight loss among continuing smokers in these groups. CONCLUSIONS: In a current, nationally representative sample, baseline BMI and CPD were important factors that contributed to the magnitude of long-term weight gain following smoking cessation. Light to moderate smokers (<15 CPD) experienced little SCA weight gain, whereas heavy smokers (?25 CPD) and those who were obese before quitting experienced the most. PMID- 26155919 TI - Weight perceptions in a population sample of English adolescents: cause for celebration or concern? AB - OBJECTIVES: To examine the proportion of normal-weight adolescents who consider themselves to be too heavy (size overestimation), and the proportion of overweight or obese adolescents who consider themselves to be about the right weight or too light (size underestimation), in large population-based samples collected over 8 years in England. METHODS: Data were from the Health Survey for England between 2005 and 2012: an annual survey of households representative of the English population. We analysed data from 4979 adolescents (2668 boys, 2311 girls) aged 13 to 15 years old whose weight status was defined as normal weight or overweight/obese based on body mass index standard deviation scores (BMI-SDS) derived from objective measurements of height and weight and using International Obesity Task Force standards. Weight perception was based on the adolescent's choice from the following descriptors: 'about the right weight', 'too heavy' or 'too light'. RESULTS: The majority of normal-weight adolescents (83% of boys, 84% of girls) correctly identified themselves as 'about the right weight'. Overestimation was uncommon, with only 7% of normal-weight teens (4% of boys, 11% of girls) identifying themselves as 'too heavy'. In contrast, only 60% of overweight/obese adolescents (53% of boys, 68% of girls) correctly identified themselves as 'too heavy', whereas 39% (47% of boys, 32% of girls) underestimated, identifying themselves as 'about the right weight' or 'too light'. There were no significant changes in BMI-SDS or body size estimation over time (2005-2012). CONCLUSIONS: Overestimation of body weight among normal-weight adolescents is relatively uncommon; potentially a cause for celebration. However, almost half of boys and a third of girls with a BMI placing them in the overweight or obese BMI range perceived themselves to be about the right weight. Lack of awareness of excess weight among overweight and obese adolescents could be a cause for concern. PMID- 26155920 TI - Insulin resistance in obesity can be reliably identified from fasting plasma insulin. AB - BACKGROUND/OBJECTIVES: Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. SUBJECTS/METHODS: We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6 (2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. RESULTS: Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 MUmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd <37.3 MUmol kg(-1) min(-1) did not differ from insulin-sensitive obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110+/-49 vs 63+/-29 pmol l(-1), P<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) (4.5+/-2.2 vs 2.7+/-1.4, P=0.004). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). CONCLUSIONS: Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings. PMID- 26155921 TI - Developmental trajectories of adiposity from birth until early adulthood and association with cardiometabolic risk factors. AB - OBJECTIVE: To identify developmental trajectories of adiposity from birth until early adulthood, and to investigate how they relate with cardiometabolic risk factors at 21 years of age. METHODS: Participants' weight and height measurements were obtained using the EPITeen cohort protocol at 13, 17 and 21 years of age, and extracted from child health books as recorded during health routine evaluations since birth. Blood pressure, triglycerides, cholesterol and insulin resistance (HOMA-IR) were assessed at 21 years. Trajectories were defined using 719 participants contributing 11 459 measurements. The individual growth curves were modelled using mixed-effects fractional polynomial, and the trajectories were estimated using normal mixture modelling for model-based clustering. Differences in cardiometabolic risk factors at 21 years according to adiposity trajectories were estimated through analysis of covariance (ANCOVA), and adjusted means are presented. RESULTS: Two trajectories-'Average body mass index (BMI) growth' (80.7%) and 'Higher BMI growth' (19.3%)-were identified. Compared with those in 'Average BMI growth', 'Higher BMI growth' participants were more frequently delivered by caesarean section, mothers were younger and had higher BMI, and parental education was lower; and at 21 years showed higher adjusted mean systolic (111.6 vs 108.3 mm Hg, P<0.001) and diastolic blood pressure (71.9 vs 68.4 mm Hg, P<0.001), and lower high-density lipoprotein cholesterol (53.3 vs 57.0 mg dl(-1), P=0.001). As there was a significant interaction between trajectories and sex, triglycerides and HOMA-IR were stratified by sex and we found significantly higher triglycerides, in males, and higher HOMA-IR in both sexes in 'Higher BMI growth' trajectory. All the differences were attenuated after adjustment for BMI at 21 years. CONCLUSIONS: In this long-term follow-up, we were able to identify two adiposity trajectories, statistically related to the BMI and cardiometabolic profile in adulthood. Our results also suggest that the impact of the adiposity trajectory on cardiometabolic profile is mediated by current BMI. PMID- 26155922 TI - Effects of desloratadine citrate disodium injection on rat models of ovalbumin induced allergic rhinitis: involvement of T-cell responses modulation. AB - BACKGROUND: Allergic rhinitis (AR) is a very common worldwide problem; patients display a number of symptoms, such as sneezing, nasal itching, and rhinorrhea, and their lifestyle is affected. Desloratadine is a novel, long-acting inhibitor of histamine. However, very little is known about the effect of desloratadine citrate disodium injection (DLC injection) on AR, and the underlying mechanisms are yet unexplored. Herein, we sought to explore the effects and mechanisms of actions of DLC injection in ovalbumin (OVA)-induced immune responses in a rat model of AR. METHODS: Sixty rats were subjected to immunization with OVA (intraperitoneal [i.p.]), followed by a nasal challenge with OVA. Drugs or saline were given daily for treatment. Nasal symptoms and histology of the nasal mucosa were examined. Cytokines such as interleukin (IL)-4, IL-12, interferon (IFN) gamma, adhesion molecules such as soluble vascular cell adhesion molecule 1 (sVCAM-1), and inducible nitric oxide synthase (iNOS) expression were assessed by enzyme-linked immunosorbent assay (ELISA) kit. Nitric oxide (NO) concentration was also measured by NO assay kit. RESULTS: DLC treatment (intravenous [i.v.]) significantly decreased the frequency of sneezing and nasal scratching and alleviated nasal inflammation by increasing the serum levels of IFN-gamma and IL 12, while lowering the expression of IL-4. Thus, DLC (i.v.) treatment led to a marked elevation in T-helper 1/T-helper 2 (Th1/Th2) ratio when administered in the AR rats. The expression of sVCAM-1, iNOS, and NO were also reversed. CONCLUSION: DLC (i.v.), given after an allergen challenge, improved Th1 cytokines level and restrained Th2 responses alleviating the symptoms of AR. Our results indicate that DLC injection may exhibit such effects through the modulation of T cell responses. PMID- 26155924 TI - Numerical and experimental investigation of light trapping effect of nanostructured diatom frustules. AB - Recent advances in nanophotonic light-trapping technologies offer promising solutions in developing high-efficiency thin-film solar cells. However, the cost effective scalable manufacturing of those rationally designed nanophotonic structures remains a critical challenge. In contrast, diatoms, the most common type of phytoplankton found in nature, may offer a very attractive solution. Diatoms exhibit high solar energy harvesting efficiency due to their frustules (i.e., hard porous cell wall made of silica) possessing remarkable hierarchical micro-/nano-scaled features optimized for the photosynthetic process through millions of years of evolution. Here we report numerical and experimental studies to investigate the light-trapping characteristic of diatom frustule. Rigorous coupled wave analysis (RCWA) and finite-difference time-domain (FDTD) methods are employed to investigate the light-trapping characteristics of the diatom frustules. In simulation, placing the diatom frustules on the surface of the light-absorption materials is found to strongly enhance the optical absorption over the visible spectrum. The absorption spectra are also measured experimentally and the results are in good agreement with numerical simulations. PMID- 26155923 TI - Quantification of Aerosol Hydrofluoroalkane HFA-134a Elimination in the Exhaled Human Breath Following Inhaled Corticosteroids Administration. AB - Inhaled corticosteroids (ICS) and beta2-agonists are the primary pharmacotherapies of asthma management. However, suboptimal medication compliance is common in asthmatics and is associated with increased morbidity. We hypothesized that exhaled breath measurements of the aerosol used in the inhaled medications might prove useful as surrogate marker for asthma medication compliance. To explore this, 10 healthy controls were recruited and randomly assigned to ICS (Flovent HFA) or short acting bronchodilators (Proventil HFA). Both inhalers contain HFA-134a as aerosol propellant. Exhaled breath sampling and pulmonary function tests were performed prior to the inhaler medication dispersion, immediately after inhalation, then at 2, 4, 6, 8, 24, and 48 hours postadministration. At baseline, mean (SD) levels of HFA-134a in the breath were 252 (156) pptv. Immediately after inhalation, HFA-134a breath levels increased to 300 * 10(6) pptv and were still well above ambient levels 24 hours postadministration. The calculated ratio of forced expiratory volume in 1 second over forced vital capacity did not change over time following inhaler administration. This study demonstrates, for the first time, that breath HFA-134a levels can be used to assess inhaler medication compliance. It may also be used to evaluate how effectively the medicine is delivered. PMID- 26155925 TI - Influence of beta-blockers on heart rate recovery and rating of perceived exertion when determining training intensity for cardiac rehabilitation. AB - BACKGROUND: The influence of beta-blockers on heart rate recovery (HRR) and rating of perceived exertion (RPE) during Phase I cardiac rehabilitation (CR) for patients with a recent episode of acute myocardial infarction (AMI) is not clear. METHODS: From October 2009 to July 2011, 105 patients with a recent episode of AMI who received a successful percutaneous coronary intervention were recruited into this study. Before entering Phase II CR, each patient underwent a cardiopulmonary exercise test (CPET), where RPE was assessed every minute and related parameters were recorded. RESULTS: The participants entering CR had relatively low mean peak oxygen consumption (VO2max). However, the peak heart rate and VO2max were lower in those taking beta-blockers. The RPE value at the ventilatory threshold (VT) was significantly higher (12.7 +/- 1.7) in participants who were taking beta-blockers relative to those who were not (11.5 +/- 1.4). The HRR value was lower (12.5 +/- 8.8) in participants who were taking beta-blockers relative to those who were not (17.0 +/- 9.1). CONCLUSION: These findings suggest that use of beta-blockers increased the RPE value at the VT. In addition, HRR was attenuated by beta-blockers. In patients who do not undergo CPET, the use of beta-blockers should be taken into consideration when using RPE for the initial exercise prescription to determine training intensity. PMID- 26155927 TI - Lessons and Perspectives on Heart Failure Management From Considerations Based on the CHART-2 Study. PMID- 26155928 TI - Maternal Death Due to Stroke Associated With Pregnancy-Induced Hypertension. PMID- 26155929 TI - New ruthenium(II) coordination compounds possessing bidentate aminomethylphosphane ligands: synthesis, characterization and preliminary biological study in vitro. AB - Addition of aminomethylphosphane P{CH2N(CH2CH2)2O}3 (), PPh2{CH2N(CH2CH2)2O} () or PPh2{CH2N(CH2CH2)2NCH2CH3} () to a methanolic solution of RuCl3 results in reduction of ruthenium(iii) ions giving finally ttt-[RuCl2()2] (), ttt-[RuCl2()2] () and ttt-[RuCl2()2] (). The synthesized complexes are the first examples of ruthenium(ii) coordination compounds possessing aminomethylphosphanes chelating via phosphorus and nitrogen atoms. They were fully characterized (NMR, ESI-MS, IR, elemental analysis, X-ray crystallography). Preliminary studies of the in vitro cytotoxicity on the A549 cell line (human lung adenocarcinoma) and interactions with human serum proteins (albumin and apotransferrin) showed moderate activity of the complexes. Interestingly, the P,N-chelation leads to formation of strained 4-membered Ru-P-C-N-Ru rings, which in the case of and undergo opening in the presence of CH3CN, which results in rearrangement to ctc [RuCl2()2(CH3CN)2] () and ctc-[RuCl2()2(CH3CN)2] (). PMID- 26155930 TI - Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment. AB - Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts <=450 cel MUl(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis. PMID- 26155931 TI - Localized pulmonary histiocytic sarcomas in Pembroke Welsh Corgi. AB - Nineteen cases of histiocytic sarcomas in Pembroke Welsh Corgi were examined histopathologically. Focal or multiple masses were detected in the lung or in regional lymph nodes, or in both lung and nodes. All neoplastic lesions had common histological features characterized by the proliferation of pleomorphic histiocytic cells combined with various inflammatory cells. Most of the pleomorphic neoplastic cells were immunopositive for human leukocyte antigen (HLA)-DR and Iba-1. The median survival time for all dogs was 133 days. In the present study, several prognostic factors, such as gender, age, single or multiple lesions, lymph node involvement at the time of diagnosis, surgical resection status and additional chemotherapy, were examined, although none of these factors approached statistical significance. Histiocytic sarcoma must be considered in the differential diagnosis of dogs with pulmonary masses, especially in the canine breed. PMID- 26155926 TI - Gene flow between Drosophila yakuba and Drosophila santomea in subunit V of cytochrome c oxidase: A potential case of cytonuclear cointrogression. AB - Introgression is the effective exchange of genetic information between species through natural hybridization. Previous genetic analyses of the Drosophila yakuba D. santomea hybrid zone showed that the mitochondrial genome of D. yakuba had introgressed into D. santomea and completely replaced its native form. Since mitochondrial proteins work intimately with nuclear-encoded proteins in the oxidative phosphorylation (OXPHOS) pathway, we hypothesized that some nuclear genes in OXPHOS cointrogressed along with the mitochondrial genome. We analyzed nucleotide variation in the 12 nuclear genes that form cytochrome c oxidase (COX) in 33 Drosophila lines. COX is an OXPHOS enzyme composed of both nuclear- and mitochondrial-encoded proteins and shows evidence of cytonuclear coadaptation in some species. Using maximum-likelihood methods, we detected significant gene flow from D. yakuba to D. santomea for the entire COX complex. Interestingly, the signal of introgression is concentrated in the three nuclear genes composing subunit V, which shows population migration rates significantly greater than the background level of introgression in these species. The detection of introgression in three proteins that work together, interact directly with the mitochondrial-encoded core, and are critical for early COX assembly suggests this could be a case of cytonuclear cointrogression. PMID- 26155932 TI - Improving early infant HIV diagnosis in Kenya: study protocol of a cluster randomized efficacy trial of the HITSystem. AB - BACKGROUND: Early infant diagnosis among human immunodeficiency virus (HIV) exposed infants is a critical component of prevention of mother-to-child transmission programs. Barriers to early infant diagnosis include poor uptake, low retention at designated re-testing intervals, delayed test results, passive systems of communication, and poor linkage to treatment. This study will evaluate the HIV Infant Tracking System (HITSystem), an eHealth intervention that streamlines communication and accountability between the key early infant diagnosis stakeholders: HIV+ mothers and their HIV-exposed infants, healthcare providers, and central laboratory personnel. It is hypothesized that the HITSystem will significantly improve early infant diagnosis retention at 9 and 18 months postnatal and the timely provision of services. METHODS/DESIGN: Using a phased cluster-randomized controlled trial design, we will evaluate the impact of the HITSystem on eight primary benchmarks in the 18-month long cascade of care for early infant diagnosis. Study sites are six government hospitals in Kenya matched on geographic region, resource level, and patient volume. Early infant diagnosis outcomes of mother-infant dyads (n = 120 per site) at intervention hospitals (n = 3) where the HITSystem is deployed at baseline will be compared to the matched control sites providing standard care. After allowing for sufficient time for enrollment and 18-month follow-up of dyads, the HITSystem will be deployed at the control sites in the end of Year 3. Primary outcomes are retention among mother-infant dyads, initiation of antiretroviral therapy among HIV-infected infants, and the proportion of services delivered within the optimal time window indicated by national and study guidelines. Satisfaction interviews with participants and providers will inform intervention improvements. Cost effectiveness analyses will be conducted to inform the sustainability of the HITSystem. Hypothesized outcomes include significantly higher retention throughout the 18-month early infant diagnosis process, significantly more services provided on-time at intervention sites, and a potential savings to the healthcare system. DISCUSSION: This study will evaluate the public health impact of the HITSystem to improve critical early infant diagnosis outcomes in low resource settings. Cost-effectiveness analyses will inform the feasibility of scale-up in other settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02072603. PMID- 26155933 TI - Protein functional features are reflected in the patterns of mRNA translation speed. AB - BACKGROUND: The degeneracy of the genetic code makes it possible for the same amino acid string to be coded by different messenger RNA (mRNA) sequences. These "synonymous mRNAs" may differ largely in a number of aspects related to their overall translational efficiency, such as secondary structure content and availability of the encoded transfer RNAs (tRNAs). Consequently, they may render different yields of the translated polypeptides. These mRNA features related to translation efficiency are also playing a role locally, resulting in a non uniform translation speed along the mRNA, which has been previously related to some protein structural features and also used to explain some dramatic effects of "silent" single-nucleotide-polymorphisms (SNPs). In this work we perform the first large scale analysis of the relationship between three experimental proxies of mRNA local translation efficiency and the local features of the corresponding encoded proteins. RESULTS: We found that a number of protein functional and structural features are reflected in the patterns of ribosome occupancy, secondary structure and tRNA availability along the mRNA. One or more of these proxies of translation speed have distinctive patterns around the mRNA regions coding for certain protein local features. In some cases the three patterns follow a similar trend. We also show specific examples where these patterns of translation speed point to the protein's important structural and functional features. CONCLUSIONS: This support the idea that the genome not only codes the protein functional features as sequences of amino acids, but also as subtle patterns of mRNA properties which, probably through local effects on the translation speed, have some consequence on the final polypeptide. These results open the possibility of predicting a protein's functional regions based on a single genomic sequence, and have implications for heterologous protein expression and fine-tuning protein function. PMID- 26155934 TI - Novel use of the Nintendo Wii board as a measure of reaction time: a study of reproducibility in older and younger adults. AB - BACKGROUND: Reaction time (RT) has been associated with falls in older adults, but is not routinely tested in clinical practice. A simple, portable, inexpensive and reliable method for measuring RT is desirable for clinical settings. We therefore developed a custom software, which utilizes the portable and low-cost standard Nintendo Wii board (NWB) to record RT. The aims in the study were to (1) explore if the test could differentiate old and young adults, and (2) to study learning effects between test-sessions, and (3) to examine reproducibility. METHODS: A young (n = 25, age 20-35 years, mean BMI of 22.6) and an old (n = 25, age >=65 years, mean BMI of 26.3) study-population were enrolled in this within- and between-day reproducibility study. A standard NWB was used along with the custom software to obtain RT from participants in milliseconds. A mixed effect model was initially used to explore systematic differences associated with age, and test-session. Reproducibility was then expressed by Intraclass Correlation Coefficients (ICC), Coefficient of Variance (CV), and Typical Error (TE). RESULTS: The RT tests was able to differentiate the old group from the young group in both the upper extremity test (p < 0.001; -170.7 ms (95%CI -209.4; 132.0)) and the lower extremity test (p < 0.001; -224.3 ms (95%CI -274.6; 173.9)). Moreover, the mixed effect model showed no significant learning effect between sessions with exception of the lower extremity test between session one and three for the young group (-35,5 ms; 4.6%; p = 0.02). A good within- and between-day reproducibility (ICC: 0.76-0.87; CV: 8.5-12.9; TE: 45.7-95.1 ms) was achieved for both the upper and lower extremity test with the fastest of three trials in both groups. CONCLUSION: A low-cost and portable reaction test utilizing a standard Nintendo wii board showed good reproducibility, no or little systematic learning effects across test-sessions, and could differentiate between young and older adults in both upper and lower extremity tests. PMID- 26155936 TI - Successful Colistin Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infection Using a Rapid Method for Determination of Colistin in Plasma: Usefulness of Therapeutic Drug Monitoring. AB - A 56-year-old woman with systemic lupus erythematosus had bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDRP). She was initially treated with imipenem-cilastatin, tobramycin, and aztreonam; however, MDRP was still detected intermittently in her plasma. Multidrug-susceptibility tests demonstrated that MDRP was susceptible only to colistin. Therefore, in addition to these antibiotics, the administration of intravenous colistin methanesulfonate, a prodrug formula of colistin, was started at a daily dose of 2.5 mg/kg (as colistin base activity). The initial dose setting was based on the patient's renal function (baseline creatinine clearance=32.7 mL/min). After initiating colistin, the patient's C-reactive protein levels gradually decreased. Blood cultures showed no evidence of MDRP on days 8, 14, and 22 after colistin initiation. However, the patient's renal function went from bad to worse owing to septic shock induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. A few days later, the trough plasma levels of colistin were 7.88 mg/L, which appeared to be higher than expected. After decreasing the colistin dose, the patient's renal function gradually improved. On the final day of colistin treatment, the plasma levels decreased to 0.60 mg/L. MDRP could not be detected in blood culture after colistin treatment. Therefore, we successfully treated a case of bloodstream infection due to MDRP by therapeutic drug monitoring (TDM) of colistin. It is suggested that the monitoring of blood colistin levels by liquid chromatography-tandem mass spectrometry can contribute to safer, more effective antimicrobial therapy of MDRP because TDM facilitates quick decisions on dose adjustments. PMID- 26155935 TI - Recent advances in Brucella abortus vaccines. AB - Brucella abortus vaccines play a central role in bovine brucellosis control/eradication programs and have been successfully used worldwide for decades. Strain 19 and RB51 are the approved B. abortus vaccines strains most commonly used to protect cattle against infection and abortion. However, due to some drawbacks shown by these vaccines much effort has been undertaken for the development of new vaccines, safer and more effective, that could also be used in other susceptible species of animals. In this paper, we present a review of the main aspects of the vaccines that have been used in the brucellosis control over the years and the current research advances in the development of new B. abortus vaccines. PMID- 26155937 TI - Acute CT perfusion changes in seizure patients presenting to the emergency department with stroke-like symptoms: correlation with clinical and electroencephalography findings. AB - AIM: To determine acute computed tomography perfusion (CTP) changes in seizure patients presenting with stroke-like symptoms and to correlate those changes with clinical presentation and electroencephalography (EEG). MATERIALS AND METHODS: The medical records of all patients who presented to the emergency department with acute stroke-like symptoms and underwent CTP (n=1085) over a 5.5-year period were reviewed. Patients were included who had primary seizure as the final diagnosis, and underwent CTP within 3 hours of symptom onset. A subset of patients had a follow-up EEG within 7 days. The perfusion changes and EEG findings were compared between different clinical presentations. RESULTS: Eighteen of 1085 patients (1.7%) who underwent CTP following an acute stroke-like presentation were included. The abnormality on CTP was usually focal, unilateral hyperperfusion - increased relative cerebral blood flow (rCBF) and volume (rCBV) (n=14/18), which most often affected the temporal lobe. Those patients who presented with a motor or speech deficit (n=12) had a higher temporal lobe rCBV, and rCBF, and lower relative mean transit time (rMTT) compared to those with non focal neurological deficit at presentation. Early EEG was available in 13 patients; a sharp-spike epileptiform EEG discharge pattern (n=5) was associated with higher temporal lobe ipsilateral rCBF and rCBV, and lower rMTT on admission CTP examination. CONCLUSION: Seizure patients who present with a unilateral motor or speech deficit most commonly have contralateral hyperperfusion in the corresponding eloquent brain regions on the acute-stage CTP examination. In such patients, epileptiform discharges on the early follow-up EEG are associated with ipsilateral hyperperfusion on the admission CTP. PMID- 26155938 TI - Adolescent school absenteeism and service use in a population-based study. AB - BACKGROUND: School absenteeism is linked to a range of health concerns, health risk behaviors and school dropout. It is therefore important to evaluate the extent to which adolescents with absenteeism are in contact with health care and other services. The aim of the current study was to investigate service use of Norwegian adolescents with moderate and high absenteeism in comparison to students with lower rates of absence. METHODS: The study employs data from a population-based study from 2012 targeting all pupils in upper secondary education in Hordaland County, Norway (the youth@hordaland-survey). A total of 8988 adolescents between the ages of 16 and 18 were included in the present study. Information on service use was based on adolescent self-report data collected in the youth@hordaland-survey. Absence data was collected using administrative data provided by the Hordaland County Council. RESULTS: High absence (defined as being absent 15% or more the past semester) was found among 10.1% of the adolescents. Compared to their peers with low absence (less than 3% absence the past semester), adolescents with high absence were more likely to be in contact with all the services studied, including mental health services (odds ratio (OR) 3.96), adolescent health clinics (OR 2.11) and their general practitioner (GP) (OR 1.94). Frequency of contact was higher among adolescents with moderate and high absence and there seems to be a gradient of service use corresponding to the level of absence. Still, 40% of the adolescents with high absence had not been in contact with any services. CONCLUSIONS: Adolescents with high absence had increased use of services, although a group of youth at risk seems to be without such contact. This finding suggests a potential to address school absenteeism through systematic collaboration between schools and health personnel. PMID- 26155939 TI - Cisplatin inhibits MEK1/2. AB - Cisplatin (cDDP) is known to bind to the CXXC motif of proteins containing a ferrodoxin-like fold but little is known about its ability to interact with other Cu-binding proteins. MEK1/2 has recently been identified as a Cu-dependent enzyme that does not contain a CXXC motif. We found that cDDP bound to and inhibited the activity of recombinant MEK1 with an IC50 of 0.28 MUM and MEK1/2 in whole cells with an IC50 of 37.4 MUM. The inhibition of MEK1/2 was relieved by both Cu+1 and Cu+2 in a concentration-dependent manner. cDDP did not inhibit the upstream pathways responsible for activating MEK1/2, and did not cause an acute depletion of cellular Cu that could account for the reduction in MEK1/2 activity. cDDP was found to bind MEK1/2 in whole cells and the extent of binding was augmented by supplementary Cu and reduced by Cu chelation. Molecular modeling predicts 3 Cu and cDDP binding sites and quantum chemistry calculations indicate that cDDP would be expected to displace Cu from each of these sites. We conclude that, at clinically relevant concentrations, cDDP binds to and inhibits MEK1/2 and that both the binding and inhibitory activity are related to its interaction with Cu bound to MEK1/2. This may provide the basis for useful interactions of cDDP with other drugs that inhibit MAPK pathway signaling. PMID- 26155940 TI - miR-29b attenuates tumorigenicity and stemness maintenance in human glioblastoma multiforme by directly targeting BCL2L2. AB - Glioblastoma multiforme (GBM) is the most common malignant brain tumor and exhibits aggressive and invasive behavior. We previously identified four miRNAs miR-29b, 494, 193a-3p, and 30e-with enhanced expression in GBM following treatment of ionizing radiation by miRNA microarray analysis. In this study, we found that only miR-29b inhibited tumor cell migration and invasion by reducing MMP-2 activity via phospho-AKT/beta-catenin signaling, and stimulated a more epithelial-like morphology. Moreover, miR-29b inhibits angiogenesis by attenuating tube formation and the expression of VEGF and Ang-2, and stemness maintenance in GBM cells, as demonstrated by decreasing neurosphere formation and cancer stem cell marker protein expression. These findings support the anti-tumor properties of miR-29b in human GBM cells. Furthermore, miR-29b expression was inversely proportional to that of BCL2L2 mRNA or protein in various cancer cell types. Interestingly, BCL2L2 mRNA is highly expressed in the mesenchymal type of GBM. To further elucidate the relationship between miR-29b and BCL2L2 in GBM, we performed co-transfection reporter assays and determined that miR-29b downregulates BCL2L2 expression by directly binding its 3'UTR. Finally, we confirmed that BCL2L2 repression is of central importance to miR-29b anti-tumor activity using functional assays to examine cell migration, invasion, angiogenesis, and stemness. From these data, we propose that miR-29b may be a useful therapeutic agent in GBM. PMID- 26155941 TI - A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors. AB - BACKGROUND: This first-in-human study evaluated AMG 208, a small-molecule MET inhibitor, in patients with advanced solid tumors. METHODS: Three to nine patients were enrolled into one of seven AMG 208 dose cohorts (25, 50, 100, 150, 200, 300, and 400 mg). Patients received AMG 208 orally on days 1 and days 4-28 once daily. The primary objectives were to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of AMG 208. RESULTS: Fifty four patients were enrolled. Six dose-limiting toxicities were observed: grade 3 increased aspartate aminotransferase (200 mg), grade 3 thrombocytopenia (200 mg), grade 4 acute myocardial infarction (300 mg), grade 3 prolonged QT (300 mg), and two cases of grade 3 hypertension (400 mg). The MTD was not reached. The most frequent grade >=3 treatment-related adverse event was anemia (n = 3) followed by hypertension, prolonged QT, and thrombocytopenia (two patients each). AMG 208 exposure increased linearly with dose; mean plasma half-life estimates were 21.4 68.7 hours. One complete response (prostate cancer) and three partial responses (two in prostate cancer, one in kidney cancer) were observed. CONCLUSIONS: In this study, AMG 208 had manageable toxicities and showed evidence of antitumor activity, particularly in prostate cancer. PMID- 26155942 TI - Chemokines CCL2, 3, 14 stimulate macrophage bone marrow homing, proliferation, and polarization in multiple myeloma. AB - We previously showed that macrophages (MPhis) infiltrate the bone marrow (BM) of patients with myeloma and may play a role in drug resistance. This study analyzed chemokines expressed by myeloma BM that are responsible for recruiting monocytes to the tumor bed. We found that chemokines CCL3, CCL14, and CCL2 were highly expressed by myeloma and BM cells, and the levels of CCL14 and CCL3 in myeloma BM positively correlated with the percentage of BM-infiltrating MPhis. In vitro, these chemokines were responsible for chemoattracting human monocytes to tumor sites and in vivo for MPhi infiltration into myeloma-bearing BM in the 5TGM1 mouse model. Surprisingly, we also found that these chemokines stimulated MPhi in vitro proliferation induced by myeloma cells and in vivo in a human myeloma xenograft SCID mouse model. The chemokines also activated normal MPhi polarization and differentiation into myeloma-associated MPhis. Western blot analysis revealed that these chemokines promoted growth and survival signaling in MPhis via activating the PI3K/Akt and ERK MAPK pathways and c-myc expression. Thus, this study provides novel insight into the mechanism of MPhi infiltration of BM and also potential targets for improving the efficacy of chemotherapy in myeloma. PMID- 26155944 TI - Psychometric properties of a brief measure of autonomy support in breast cancer patients. AB - BACKGROUND: The Health Care Climate Questionnaire measures patient perceptions of their clinician's autonomy supportive communication. We sought to evaluate the psychometric properties of a modified brief version of the Health Care Climate Questionnaire (mHCCQ) adapted for breast cancer patients. METHODS: We surveyed 235 women aged 20-79 diagnosed with breast cancer within the previous 18 months at two cancer specialty centers using a print questionnaire. Patients completed the mHCCQ for their surgeon, medical oncologist, and radiation oncologist separately, as well as the overall treatment experience. Exploratory factor analysis (EFA) using principal components was used to explore the factor structure. RESULTS: One hundred sixty out of 235 (68.1%) women completed the survey. Mean age was 57 years and time since diagnosis was 12.6 months. For surgeon, medical oncologist, and radiation oncologist ratings separately, as well as overall treatment, women rated 6 dimensions of perceived physician autonomy support. Exploratory factor analysis indicated a single factor solution for each clinician type and for the overall experience. Further, all six items were retained in each clinician subscore. Internal consistency was 0.93, 0.94, 0.97, and 0.92 for the overall, surgeon, medical oncologist, and radiation oncologist scales, respectively. Hierarchical factor analysis demonstrated that a summary score of the overall treatment experience accounts for only 52% of the total variance observed in ratings of autonomy support for the three provider types. CONCLUSIONS: These results describe the first use of the mHCCQ in cancer patients. Ratings of the overall treatment experience account for only half of the variance in ratings of autonomy support, suggesting that patients perceive and report differences in communication across provider types. Future research is needed to evaluate the relationship between physician communication practices and the quality of decision making, as well as other outcomes among cancer patients. PMID- 26155943 TI - Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis. AB - Pathological angiogenesis is a hallmark of many diseases. We demonstrated that TR3/Nur77 is an excellent target for pro-angiogenesis and anti-angiogenesis therapies. Here, we report that TR3 transcriptionally regulates endothelial cell migration, permeability and the formation of actin stress fibers that is independent of RhoA GTPase. 1) Amino acid residues 344-GRR-346 and de phosphorylation of amino acid residue serine 351 in the DNA binding domain, and 2) phosphorylation of amino acid residues in the 41-61 amino acid fragment of the transactivation domain, of TR3 are required for its induction of the formation of actin stress fibers, cell proliferation, migration and permeability. The 41-61 amino acid fragment contains one of the three potential protein interaction motifs in the transactivation domain of TR3, predicted by computational modeling and analysis. These studies further our understanding of the molecular mechanism, by which TR3 regulates angiogenesis, identify novel therapeutic targeted sites of TR3, and set the foundation for the development of high-throughput screening assays to identify compounds targeting TR3/Nur77 for pro-angiogenesis and anti angiogenesis therapies. PMID- 26155945 TI - Cross-Sectional Study of the Impact of a Natural Disaster on the Delivery of Gynecologic Oncology Care. AB - OBJECTIVE: We aimed to compare access to gynecologic oncology care at a private and a city hospital, both of which closed for a period of time because of Hurricane Sandy. METHODS: This was a cross-sectional study of gynecologic oncology chemotherapy, radiotherapy, and surgical patients from October 29, 2012 (the eve of the storm), to February 7, 2013 (the reopening of the city hospital). New referrals during this time were excluded. Delays in chemotherapy, radiotherapy, and surgery were compared. RESULTS: Analysis included 113 patients: 59 private patients (52.2%) and 54 city patients (47.8%). Of the private patients, 33/59 received chemotherapy (55.9%), 1/59 received radiotherapy (1.7%), and 28/59 had planned surgery (47.5%). Of the city patients, 40/54 received chemotherapy (74.1%), 7/54 received radiotherapy (12.3%), and 18/54 had planned surgery (33.3%). The mean delay in chemotherapy was 7.6 days at the private hospital and 21.7 days at the city hospital (P=0.0004). The mean delay in scheduled surgery was 14.2 days at the private hospital and 22.7 days at the city hospital (P=0.3979). The mean delay in radiotherapy was 0.0 days at the private hospital and 25.0 days at the city hospital (P=0.0046). Loss to follow-up rates were 3/59 of the private patients (5.1%) and 3/54 of the city patients (5.6%). CONCLUSIONS: Gynecologic oncology care was maintained during a natural disaster despite temporary closure and relocation of services. Disparity in care was in access to chemotherapy. PMID- 26155946 TI - Aspirin and heparin in pregnancy. AB - INTRODUCTION: A pro-coagulant state during pregnancy can be involved in the occurrence of gestational vascular complications (GVCs) and venous thromboembolism (VTE). AREAS COVERED: Antithrombotic drugs are used to prevent GVCs and VTE. Aspirin is not efficacious to prevent recurrences in women with previous early loss, while it can prevent pre-eclampsia in some groups of women. Heparins are not effective in the prevention of early recurrent loss and there is uncertainty about their efficacy in women carrying inherited thrombophilias. They could be efficacious in the prevention of GVCs in carriers of inherited thrombophilias, as GVCs have heterogeneous causes, and future studies have to focus on more homogeneous groups of patients. Not enough data are available regarding prophylaxis with heparins to prevent pregnancy-related VTE, but an accurate risk stratification of women during pregnancy and puerperium is crucial for administering prophylaxis in moderate-/high-risk women. Aspirin does not improve live births after assisted reproductive technologies, while heparins increase the number of clinical pregnancies and live births. EXPERT OPINION: Aspirin is efficacious in the prevention of GVCs in women at risk for pre eclampsia and in those with antiphospholipid antibodies syndrome. Heparins could give benefit to women at risk for GVCs and/or pregnancy-related VTE. PMID- 26155947 TI - Capsosomes as Long-Term Delivery Vehicles for Protein Therapeutics. AB - We report the preparation of polymer capsules containing liposomal subcompartments, termed capsosomes, and their ability for the sustained delivery of protein therapeutics. Capsosomes were formed through the layer-by-layer (LbL) assembly of polymers and protein-loaded liposomes, followed by the formation of a capsule membrane based on disulfide cross-linked poly(methacrylic acid). The loading capacities of a model cargo (lysozyme) and brain-derived neurotrophic factor (BDNF), an important neurotrophin that has significant physiological functions on the nervous system, were determined, and the long-term release kinetics of the proteins was investigated in simulated physiological conditions. The capsosomes exhibited protein loading and release behavior that can be tuned by the lipid composition of the liposomal compartments, where inclusion of anionic lipids resulted in enhanced protein loading and slower release over the course of 80 days. These findings highlight the potential of capsosomes for the long-term delivery of protein therapeutics. PMID- 26155948 TI - A cuboctahedral platinum (Pt79) nanocluster enclosed by well defined facets favours di-sigma adsorption and improves the reaction kinetics for methanol fuel cells. AB - The methanol dehydrogenation steps are studied very systematically on the (111) facet of a cuboctahedral platinum (Pt79) nanocluster enclosed by well-defined facets. The various intermediates formed during the methanol decompositions are adsorbed at the edge and bridge site of the facet either vertically (through C- and O-centres) or in parallel. The di-sigma adsorption (in parallel) on the (111) facet of the nanocluster is the most stable structure for most of the intermediates and such binding improves the interaction between the substrate and the nanocluster and thus the catalytic activity. The reaction thermodynamics, activation barrier, and temperature dependent reaction rates are calculated for all the successive methanol dehydrogenation steps to understand the methanol decomposition mechanism, and these values are compared with previous studies to understand the catalytic activity of the nanocluster. We find the catalytic activity of the nanocluster is excellent while comparing with any previous reports and the methanol dehydrogenation thermodynamics and kinetics are best when the intermediates are adsorbed in a di-sigma manner. PMID- 26155949 TI - A statistical frame based TDMA protocol for human body communication. AB - BACKGROUND: Human body communication (HBC) using the human body as the transmission medium, which has been regarded as one of the most promising short range communications in wireless body area networks (WBAN). Compared to the traditional wireless networks, two challenges are existed in HBC based WBAN. (1) Its sensor nodes should be energy saving since it is inconvenient to replace or recharge the battery on these sensor nodes; (2) the coordinator should be able to react dynamically and rapidly to the burst traffic triggered by sensing events. Those burst traffic conditions include vital physical signal (electrocardiogram, electroencephalogram etc.) monitoring, human motion detection (fall detection, activity monitoring, gesture recognition, motion sensing etc.) and so on. To cope with aforementioned challenges, a statistical frame based TDMA (S-TDMA) protocol with multi-constrained (energy, delay, transmission efficiency and emergency management) service is proposed in this paper. METHODS: The scenarios where burst traffic is often triggered rapidly with low power consumption and low delay is handled in our proposed S-TDMA. A beacon frame with the contained synchronous and poll information is designed to reduce the possibility of collisions of request frames. A statistical frame which broadcasts the unified scheduling information is adopted to avoid packet collisions, idle listening and overhearing. Dynamic time slot allocation mechanism is presented to manage the burst traffic and reduce the active period in each beacon period. An emergency mechanism is proposed for vital signals to be transmitted. The theory analysis is proceed and the result is evaluated in the hardware platform. RESULTS: To verify its feasibility, S-TDMA was fully implemented on our independently-developed HBC platform where four sensor nodes and a coordinator are fastened on a human body. Experiment results show that S-TDMA costs 89.397 mJ every 20 s when the payload size is 122 bytes, 9.51% lower than Lightweight MAC (LMAC); the average data latency of S-TDMA is 6.3 ms, 7.02% lower than Preamble-based TDMA (PB-TDMA); the transmission efficiency of S-TDMA is 93.67%, 4.83% higher than IEEE 802.15.6 carrier sense multiple access/collision avoidance (CSMA/CA) protocol. CONCLUSIONS: With respect to the challenges of HBC based WBANs, a novel S-TDMA protocol was proposed in this paper. Compared to the traditional protocols, the results demonstrate that S-TDMA successfully meets the delay and transmission efficiency requirements of HBC while keeping a low energy consumption. We also believe that our S-TDMA protocol will promote development of HBC in wearable applications. PMID- 26155952 TI - Therapeutic ultrasound treatment for excessive skin on the upper arms due to extensive weight loss after bariatric surgery: A single blind, randomised, controlled trial. AB - BACKGROUND: Excessive skin is a side-effect of massive weight loss. The only evidence-based treatment for excessive skin is plastic surgery. Non-invasive treatments, therefore, need to be evaluated. The aim of this study was to investigate effects of therapeutic ultrasound treatment on excess skin on the upper arms after bariatric surgery. METHOD: Fourteen patients were randomised to receive five treatments, each lasting for 30 minutes with active ultrasound treatment by CellsonicTM (Cellsonic Ltd) on one arm. The other arm served as control. The effect was evaluated objectively by measuring arm volume, circumference, and ptosis, and subjectively by a questionnaire where the patients assessed the effect of the treatment and amount and/or discomfort of the excess skin. RESULT: No statistical differences were observed in the objectively measured variables. Some patients reported perceived effects and a majority reported positive experiences of the treatment. No side-effects were reported. CONCLUSION: This study could not find any objectively measured effect of ultrasound treatment on excessive skin after bariatric surgery. However, participants experienced relief of symptoms associated with excess skin, such as pain, looseness, and decreased skin burst, which indicates that ultrasonic treatment of patients with excessive skin should be further investigated. PMID- 26155950 TI - Can the breast screening appointment be used to provide risk assessment and prevention advice? AB - Breast cancer risk is continuing to increase across all societies with rates in countries with traditionally lower risks catching up with the higher rates in the Western world. Although cure rates from breast cancer have continued to improve such that absolute numbers of breast cancer deaths have dropped in many countries despite rising incidence, only some of this can be ascribed to screening with mammography, and debates over the true value of population-based screening continue. As such, enthusiasm for risk-stratified screening is gaining momentum. Guidelines in a number of countries already suggest more frequent screening in certain higher-risk (particularly, familial) groups, but this could be extended to assessing risks across the population. A number of studies have assessed breast cancer risk by using risk algorithms such as the Gail model, Tyrer-Cuzick, and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), but the real questions are when and where such an assessment should take place. Emerging evidence from the PROCAS (Predicting Risk Of Cancer At Screening) study is showing not only that it is feasible to undertake risk assessment at the population screening appointment but that this assessment could allow reduction of screening in lower-risk groups in many countries to 3-yearly screening by using mammographic density-adjusted breast cancer risk. PMID- 26155953 TI - A Privacy Preservation Model for Health-Related Social Networking Sites. AB - The increasing use of social networking sites (SNS) in health care has resulted in a growing number of individuals posting personal health information online. These sites may disclose users' health information to many different individuals and organizations and mine it for a variety of commercial and research purposes, yet the revelation of personal health information to unauthorized individuals or entities brings a concomitant concern of greater risk for loss of privacy among users. Many users join multiple social networks for different purposes and enter personal and other specific information covering social, professional, and health domains into other websites. Integration of multiple online and real social networks makes the users vulnerable to unintentional and intentional security threats and misuse. This paper analyzes the privacy and security characteristics of leading health-related SNS. It presents a threat model and identifies the most important threats to users and SNS providers. Building on threat analysis and modeling, this paper presents a privacy preservation model that incorporates individual self-protection and privacy-by-design approaches and uses the model to develop principles and countermeasures to protect user privacy. This study paves the way for analysis and design of privacy-preserving mechanisms on health related SNS. PMID- 26155954 TI - Agreement between physicians and liaison psychiatrists on depression in old age patients of a general hospital: influence of symptom severity, age and personality. AB - OBJECTIVE: Comorbid depressive episodes are common among general hospital inpatients. However, existing evidence shows that depression is often poorly recognized in patients aged over 60 years. The aim of the study was first to determine the degree of agreement between primary care physicians' and liaison psychiatrists' evaluation of depression, and second, to analyze how patients' clinical presentation and personality traits influence this degree of agreement. METHODS: Agreement was defined as the matching of the physicians' initial referral for depressive mood and the actual diagnosis of a major depressive disorder evaluated by the consultation-liaison service in 148 inpatients aged 60+ years. Nature and severity of psychiatric symptoms were rated on the HoNOS65+ scale and patients' personality traits were assessed with the Big Five Inventory. RESULTS: Forty percent of the patients referred for depressive mood were indeed diagnosed with major depression. Agreement between physicians and psychiatrists was most likely in patients with more severe depressive symptoms and younger age. In contrast, risk for non-agreement was increased for patients with more open personalities, yet lower levels of neuroticism, who were referred for depressive mood even though they presented another or even no psychiatric disorder. CONCLUSION: These data reveal that the detection of late-life depression in general hospitals may be critically influenced by age, symptoms severity and personality traits. PMID- 26155955 TI - Endoscopic ultrasonography-guided transjejunal drainage for postoperative pancreatic fistula using forward-viewing echoendoscope. AB - There are few reports on endoscopic ultrasonography (EUS)-guided transjejunal drainage. Here, we report a case with postoperative pancreatic fistula treated by endoscopic transjejunal drainage using a forward-viewing (FV) echoendoscope. A 69 year-old woman who had undergone pancreaticoduodenectomy was admitted because of pancreatic fistula. Placement of plastic stents into the pancreatic duct using a double-balloon enteroscope and EUS-guided transgastric drainage failed. We attempted EUS-guided transjejunal drainage using an FV echoendoscope that can advance through the acute-angled intestinal tract safely, and drainage was performed. There were no complications, and follow-up computed tomography showed complete resolution. PMID- 26155956 TI - NMR-Based Metabolomics Separates the Distinct Stages of Disease in a Chronic Relapsing Model of Multiple Sclerosis. AB - Relapsing experimental allergic encephalomyelitis (Cr-EAE) is commonly used to explore the pathogenesis and efficacy of new therapies for MS, but it is unclear whether the metabolome of Cr-EAE is comparable to human multiple sclerosis (MS). For MS, the diagnosis and staging can be achieved by metabolomics on blood using a combination of magnetic resonance spectroscopy and partial least squares discriminant analysis (PLS-DA). Here, we sought to discover whether this approach could be used to differentiate between sequential disease states in Cr-EAE and whether the same metabolites would be discriminatory. Urine and plasma samples were obtained at different time-points from a clinically relevant model of MS. Using PLS-DA modelling for the urine samples furnished some predictive models, but could not discriminate between all disease states. However, PLS-DA modelling of the plasma samples was able to distinguish between animals with clinically silent disease (day 10, 28) and animals with active disease (day 14, 38). We were also able to distinguish Cr-EAE mice from naive mice at all-time points and control mice, treated with complete Freund's adjuvant alone, at day 14 and 38. Key metabolites that underpin these models included fatty acids, glucose and taurine. Two of these metabolites, fatty acids and glucose, were also key metabolites in separating relapsing-remitting MS from secondary-progressive MS in the human study. These results demonstrate the sensitivity of this metabolomics approach for distinguishing between different disease states. Furthermore, some, but not all, of the changes in metabolites were conserved in humans and the mouse model, which could be useful for future drug development. PMID- 26155957 TI - Independent correlates of urinary albumin excretion within the normoalbuminuric range in patients with type 2 diabetes: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. AB - AIMS: Within the normoalbuminuric range, low albuminuria (LA, 10-29 mg/24 h) is associated with higher adverse cardiovascular and renal outcomes than normal albuminuria (NA, <10 mg/24 h). This cross-sectional analysis of the cohort from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study was aimed at assessing the independent correlates of LA versus NA in patients with type 2 diabetes. METHODS: This analysis involved 11,538 normoalbuminuric patients (73.2 % of the entire RIACE cohort): 6023 (52.2 %) with NA and 5515 (47.8 %) with LA. Binary logistic regression analysis with backward conditional variable selection was applied to assess the independent correlates of LA versus NA. RESULTS: Compared with NA subjects, LA patients were more frequently males, older and with family history of hypertension, had longer diabetes duration, lower HDL cholesterol, and higher haemoglobin (Hb) A1c, triglycerides, and blood pressure (BP), use of anti-hyperglycaemic and anti hypertensive drugs, and prevalence of metabolic syndrome, retinopathy, chronic kidney disease, any cardiovascular disease, myocardial infarction, and coronary and peripheral events. Men with LA were also more frequently current or former smokers and had higher body mass index, waist circumference, and non-HDL cholesterol. Independent correlates of LA were age (OR 1.018), family history of hypertension (OR 1.321), smoking status (former, OR 1.158; current, OR 1.237), HbA1c (OR 1.062), waist circumference (OR 1.050), triglycerides (OR 1.001), and diastolic BP (OR 1.014), together with use of anti-hyperglycaemic and anti hypertensive agents. CONCLUSIONS: Several risk factors are associated with increased albuminuria within the normoalbuminuric range. As most of these factors are potentially modifiable, treating them aggressively might reduce the excess risk associated with LA. TRIAL REGISTRATION: NCT00715481; www.ClinicalTrials.gov . PMID- 26155958 TI - Polypharmacy in elderly patients with type 2 diabetes receiving oral antidiabetic treatment. AB - AIM: Polypharmacy in older diabetics can have detrimental effects linked to poor adherence and the risk of drug interaction or more serious/frequent side effects. The aim of this study was to identify the characteristics associated with polypharmacy in a cohort of elderly diabetic patients being treated with oral hypoglycemic agents. METHODS: The study population consisted of 1342 diabetic patients consecutively enrolled in 57 diabetes centers in Italy participating in the METABOLIC Study. Patients meeting the following inclusion criteria were enrolled: diagnosis of type 2 diabetes mellitus, age >=65 years, and receiving oral antidiabetic treatment. Data concerning diabetes duration and complications, the medications the patients were taking, and the number of hypoglycemic events were registered. Multidimensional impairment was assessed using the Multidimensional Prognostic Index. RESULTS: The mean age of the participants was 73.3 +/- 5.5 years. Polypharmacy, defined as being prescribed contemporaneously at least five drugs, was found in 57.1 % of the study population. According to a multivariable logistic model, the female gender was significantly associated with polypharmacy, as were living in Northern Italian regions, diabetes duration longer than 4 years, and having a body mass index >=30 kg/m(2). Comorbidities, diabetes complications, a better cognitive performance on the Short Portable Mental Status Questionnaire, and being malnourished/at risk of malnourishment according to the mini nutritional assessment were associated with polypharmacy. CONCLUSIONS: Polypharmacy, a condition that may lead to many potential detrimental outcomes in older diabetic subjects, was significantly associated with some risk factors that may be useful to identify subjects at risk. PMID- 26155959 TI - iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines. AB - Computational vaccine design, also known as computational vaccinology, encompasses epitope mapping, antigen selection and immunogen design using computational tools. The iVAX toolkit is an integrated set of tools that has been in development since 1998 by De Groot and Martin. It comprises a suite of immunoinformatics algorithms for triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, eliminating regulatory T cell epitopes, and optimizing antigens for immunogenicity and protection against disease. iVAX has been applied to vaccine development programs for emerging infectious diseases, cancer antigens and biodefense targets. Several iVAX vaccine design projects have had success in pre-clinical studies in animal models and are progressing toward clinical studies. The toolkit now incorporates a range of immunoinformatics tools for infectious disease and cancer immunotherapy vaccine design. This article will provide a guide to the iVAX approach to computational vaccinology. PMID- 26155960 TI - Spatial and Seasonal Variations of Total Petroleum Hydrocarbon in Surface Water and Sediment in Pearl River Delta. AB - A field study in the Pearl River Delta of China was conducted in order to describe to the spatial and seasonal variation of occurrence and concentrations of total petroleum hydrocarbon (TPH) in surface water and sediments. Petroleum hydrocarbons and isoprenoid alkanes were quantified by UV spectroscopy and gas chromatography with a mass selective detector. The concentrations of TPH ranged from 4.3 to 68.7 ug L(-1) in surface water, and from 66.6 to 1445 ug g(-1) in surface sediments. The ratios of pristine to phytane suggested that the main sources of TPH in the sediment were petroleum importation. The highest concentrations of TPH were present in the spring season. When compared with results from previous studies, it can be concluded that the Pearl River Delta was moderately polluted by TPH. No statistically significant correlations were observed between the concentrations of TPH in surface water and sediments. PMID- 26155961 TI - Tolerance to Ammonia of Thulinius ruffoi (Bertolani, 1981), a Tardigrade Isolated from a Sewage Treatment Plant. AB - The acute toxicity of ammonia on Thulinius ruffoi (Bertolani, 1981), a eutardigrade isolated from a small waste water treatment plant (WWTP) in Poland, was estimated. Our results show that no active individuals survived a 24 h exposure to solutions equal to or higher than 125 mg/L of total ammonia nitrogen (NH3-N + NH4 (+)-N), which, under the conditions in our experiment, was equivalent to 1.17 mg/L of un-ionised ammonia (NH3). The LC50 concentration of total ammonia nitrogen was equal to 52 mg/L (or 0.65 mg/L un-ionised ammonia). Given that the norms for the concentration of ammonia in treated waters leaving WWTPs are usually several times lower than the LC50 for T. ruffoi, this species does not seem to be a good bioindicator candidate for WWTPs. In this paper we also note that various ecotoxicological studies use different methodological approaches and we suggest that a more uniform methodology may aid interspecific comparisons of LC50 values. PMID- 26155962 TI - Total Mercury in Six Antarctic Notothenioid Fishes. AB - We analyzed white muscle samples from six species of Antarctic fish (suborder Notothenioidei) collected in 2011 from McMurdo Sound, Ross Sea, Antarctica, to assess levels of total mercury (THg). Gymnodraco acuticeps and Trematomus bernacchii exhibited the highest concentrations of THg followed by Trematomus pennellii, Trematomus nicolai, Trematomus newnesi and Pagothenia borchgrevinki, (71.3, 53.9+/-32.1, 45.8+/-27.3, 37.2+/-18.6, 35.7+/-23.6, and 21.9+/-2.8 ng/g wet weight, respectively). The results from this study suggest that THg has the potential to bioaccumulate from various marine Antarctic ecosystems into biota. PMID- 26155963 TI - Effects of Nano Silver Oxide and Silver Ions on Growth of Vigna radiata. AB - Transformation of silver oxide nanoparticles (nano-Ag2O) to silver nanoparticles (nano-Ag) and silver ions in environment is possible which might pose toxicity to plants and other species. The objective of this study was to study effects of nano-Ag2O and silver ions on growth of Mung bean (Vigna radiata) seedlings. V. radiata seeds were exposed to nano-Ag2O and silver ions (concentration range: 4.3 * 10(-7), 4.3 * 10(-6), 4.3 * 10(-5), 4.3 * 10(-4), and 4.3 * 10(-3) mol/L) for 6 days. Root length, shoot length and dry weight of seedlings were found to decrease due to exposure of nano-Ag2O and silver ions. These findings indicate silver ions to be more toxic to V. radiata seeds than nano-Ag2O. Silver content in seedlings was found to increase with increasing concentrations of nano-Ag2O and silver ions. Overall, findings of the present study add to the existing knowledge of phytotoxicity of silver-based nanoparticles of different chemical compositions to V. radiata seeds and need to be considered during use of nanoparticles-contaminated water for irrigation purposes. PMID- 26155964 TI - Determination and Method Validation of the New Sulfone Fungicide 2-(4 Fluorophenyl)-5-Methylsulfonyl-1,3,4-Oxadiazole in Tomato and Soil by UPLC in Field Trial Samples from Guizhou Province, China. AB - A new method was developed and validated for the determination of 2-(4 fluorophenyl)-5-methylsulfonyl-1,3,4-oxadiazole (jiahuangxianjunzuo, JHXJZ) by ultra-performance liquid chromatography equipped with photo-diode array detector. JHXJZ from tomato and soil was extracted with ethyl acetate without further cleanup. The limits of detection and quantification of JHXJZ were 0.0083 and 0.025 mg kg(-1) in tomato, 0.0017 and 0.005 mg kg(-1) in soil, respectively. The average recoveries of tomato and soil were studied at three spiked levels and ranged from 84.51 % to 101.30 % and 85.30 % to 101.53 %, respectively, with relative standard deviations of 2.61 %-4.13 % and 1.21 %-4.80 %, respectively. The results indicated that the reported method could meet the requirement for the analysis of JHXJZ in trace amount in tomato and soil. PMID- 26155966 TI - Lithium Induces Glycogen Accumulation in Salivary Glands of the Rat. AB - Lithium is administered for the treatment of mood and bipolar disorder. The aim of this study was to verify whether treatment with different concentrations of lithium may affect the glycogen metabolism in the salivary glands of the rats when compared with the liver. Mobilization of glycogen in salivary glands is important for the process of secretion. Two sets of experiments were carried out, that is, in the first, the rats received drinking water supplemented with LiCl (38,25 and 12 mM of LiCl for 15 days) and the second experiment was carried out by intraperitoneal injection of LiCl solution (12 mg/kg and 45 mg LiCl/kg body weight) for 3 days. The active form of glycogen phosphorylase was not affected by treatment with LiCl considering the two experiments. The active form of glycogen synthase presented higher activity in the submandibular glands of rats treated with 25 and 38 mM LiCl and in the liver, with 25 mM LiCl. Glycogen level was higher than that of control in the submandibular glands of rats receiving 38 and 12 mM LiCl, in the parotid of rats receiving 25 and 38 mM, and in the liver of rats receiving 12 mM LiCl. The absolute value of glycogen for the submandibular treated with 25 mM LiCl, and the liver treated with 38 mM LiCl, was higher than the control value, although not statistically significant for these tissues. No statistically significant difference was found in the submandibular and parotid salivary glands for protein concentration when comparing experimental and control groups. We concluded that LiCl administered to rats influences the metabolism of glycogen in salivary glands. PMID- 26155965 TI - Validation of a Metallomics Analysis of Placenta Tissue by Inductively-Coupled Plasma Mass Spectrometry. AB - Trace elements can play an important role in maternal health and fetal development, and deficiencies in some essential minerals including zinc and copper have been correlated in some individuals to the development of birth defects and adverse health outcomes later in life. The exact etiology of conditions like preeclampsia and the effects of fetal exposure to toxic metals has not been determined, making the assessment of trace element levels crucial to the elucidation of the causes of conditions like preeclampsia. Previous studies analyzing serum and placenta tissue have produced conflicting findings, suggesting the need for a robust, validated sample preparation and analysis method for the determination of trace elements in placenta. In this report, an acid digestion method and analysis by ICP-MS for a broad metallomics/mineralomics panel of trace elements is developed and validated over three experimental days for inter- and intraday precision and accuracy, linear range, matrix impact, and dilution verification. Spike recovery experiments were performed for the essential elements chromium (Cr), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), and zinc (Zn), and the toxic elements arsenic (As), cadmium (Cd), and lead (Pb) at levels equal to and in excess of native concentrations in control placenta tissue. The validated method will be essential for the development of scientific studies of maternal health and toxic metal exposure effects in childhood. PMID- 26155967 TI - Semantic richness effects in lexical decision: The role of feedback. AB - Across lexical processing tasks, it is well established that words with richer semantic representations are recognized faster. This suggests that the lexical system has access to meaning before a word is fully identified, and is consistent with a theoretical framework based on interactive and cascaded processing. Specifically, semantic richness effects are argued to be produced by feedback from semantic representations to lower-level representations. The present study explores the extent to which richness effects are mediated by feedback from lexical- to letter-level representations. In two lexical decision experiments, we examined the joint effects of stimulus quality and four semantic richness dimensions (imageability, number of features, semantic neighborhood density, semantic diversity). With the exception of semantic diversity, robust additive effects of stimulus quality and richness were observed for the targeted dimensions. Our results suggest that semantic feedback does not typically reach earlier levels of representation in lexical decision, and further reinforces the idea that task context modulates the processing dynamics of early word recognition processes. PMID- 26155968 TI - Incidence and risk factors for heterotopic ossification after total hip arthroplasty: a meta-analysis. AB - BACKGROUND: This study aims to quantitatively summarize risk factors associated with heterotopic ossification after total hip arthroplasty. METHODS: The computerized and additional manual searches were performed in Medline, Embase, CNKI, and Cochrane central database (all through March 2014) for potential studies. Studies eligible had to meet the quality assessment criteria by Newcastle-Ottawa Scale and to evaluate the risk factors for heterotopic ossification after total hip arthroplasty. Two reviewers independently extracted the relevant data and any disagreement was solved by consensus. Stata11.0 was used to perform all the statistical analyses. RESULTS: Fourteen studies involving 6468 cases with total hip arthroplasty and 1939 heterotopic ossification (HOs) (30.0 %) were eligible and included in this meta-analysis. Our meta-analysis identified the significant increased risk factors for HO were male gender [odds ratio (OR) 2.11; 95 % confidence interval (CI) 1.80-2.48)], cemented implant (OR 1.48; 95 % CI 1.00-2.17), bilateral operations (OR 1.74; 95 % CI 1.24-2.45), ankylosing spondylitis (OR 1.90; 95 % CI 1.07-3.37) and ankylosed hip (OR 9.85; 95 % CI 2.61-37.24). Rheumatoid arthritis was protective for the development of HO (OR 0.51; 95 % CI 0.33-0.80). The other variables including age, use of NSAIDs, femoral neck fracture, previous hip fracture, hypertrophic osteoarthritis and osteophytes were identified not as the risk factors for development of HO (P > 0.05). CONCLUSION: Patients involved with the above-mentioned medical conditions should be carefully paid close attention by surgeons to reduce HO after total hip arthroplasty. LEVEL OF EVIDENCE: Level II, meta-analysis. PMID- 26155969 TI - Mitochondrial genome of Micrura bella (Nemertea: Heteronemertea), the largest mitochondrial genome known to phylum Nemertea. AB - The complete mitochondrial genome (mitogenome) of Micrura bella was sequenced and analyzed. Being the largest mitogenome known to phylum Nemertea, the genome is 16 847 bp in length. It encodes 37 genes typical to metazoan mitogenomes and has the same gene arrangement with the other Heteronemertea mitogenomes sequenced to date. The genome has the maximal number of non-coding nucleotides (2037 bp at 25 sites) in Nemertea mitogenomes, among which two large non-coding regions were found (507 and 508 bp, respectively). PMID- 26155970 TI - Phylogenetic relationships linking Duttaphrynus (Amphibia: Anura: Bufonidae) species based on 12S and 16S rDNA sequences. AB - Genus Duttaphrynus (Amphibia: Anura: Bufonidae) is endemic to southwestern and southern China and throughout southern Asia. Duttaphrynus phylogeny was also under debate for many years. 12S and 16S rDNAs help us to elucidate Duttaphrynus phylogeny. PMID- 26155971 TI - Human papillomavirus vaccination of the daughters of obstetricians and gynecologists in Japan. AB - BACKGROUND: Most adolescents in Japan have recently been refraining from receiving the human papillomavirus (HPV) vaccine, following media reports of adverse medical events surrounding the vaccination and suspension of the Japanese governmental recommendation. We have previously reported that HPV vaccination of young girls is heavily influenced by guidance from their physicians concerning the vaccine and by the knowledge and attitude of the girls' mothers towards cervical cancer. However, it has been unclear as to how the obstetricians and gynecologists were themselves affected by the negative media reports. METHODS: A questionnaire, including questions about their working status, attitudes toward HPV vaccination and about cervical cancer, and the HPV vaccination status of their daughters, was posted to obstetricians and gynecologists. RESULTS: None of the daughters of the responding obstetrician and gynecologists received the HPV vaccination after the announced suspension of the governmental recommendation for the vaccine. The number who received the HPV vaccine in the 6th to 9th grade in 2014 was significantly lower than those in 2012 (p = 0.012). However, 64.7 % of the responders whose daughters were eligible and in the 6th to 12th grade still intended to vaccinate their daughters in the future. Of the responders, 65 % also intended to recommend vaccination to their teenage patients. CONCLUSIONS: Our study revealed that obstetricians and gynecologists, like the general population, were negatively influenced by media reports of the adverse effect of the HPV vaccine and the suspension of the governmental recommendation. However, their intention to vaccinate their daughters was much higher than that of the general population. Restart of the governmental recommendation for HPV vaccines and better education about the HPV vaccine, including its adverse effects, and about cervical cancer and cervical cancer screening, are strongly recommended, for both the general public and for doctors, for improved prevention of cervical cancer. PMID- 26155973 TI - Exploration of the chlorpyrifos escape pathway from acylpeptide hydrolases using steered molecular dynamics simulations. AB - Acylpeptide hydrolases (APH) catalyze the removal of an N-acylated amino acid from blocked peptides. APH is significantly more sensitive than acetylcholinesterase, a target of Alzheimer's disease, to inhibition by organophosphorus (OP) compounds. Thus, OP compounds can be used as a tool to probe the physiological functions of APH. Here, we report the results of a computational study of molecular dynamics simulations of APH bound to the OP compounds and an exploration of the chlorpyrifos escape pathway using steered molecular dynamics (SMD) simulations. In addition, we apply SMD simulations to identify potential escape routes of chlorpyrifos from hydrolase hydrophobic cavities in the APH-inhibitor complex. Two previously proposed APH pathways were reliably identified by CAVER 3.0, with the estimated relative importance of P1 > P2 for its size. We identify the major pathway, P2, using SMD simulations, and Arg526, Glu88, Gly86, and Asn65 are identified as important residues for the ligand leaving via P2. These results may help in the design of APH-targeting drugs with improved efficacy, as well as in understanding APH selectivity of the inhibitor binding in the prolyl oligopeptidase family. PMID- 26155972 TI - Future Directions for Dissemination and Implementation Science: Aligning Ecological Theory and Public Health to Close the Research to Practice Gap. AB - Dissemination and implementation science (DI) has evolved as a major research model for children's mental health in response to a long-standing call to integrate science and practice and bridge the elusive research to practice gap. However, to address the complex and urgent needs of the most vulnerable children and families, future directions for DI require a new alignment of ecological theory and public health to provide effective, sustainable, and accessible mental health services. We present core principles of ecological theory to emphasize how contextual factors impact behavior and allow for the reciprocal impact individuals have on the settings they occupy, and an alignment of these principles with a public health model to ensure that services span the prevention to intervention continuum. We provide exemplars from our ongoing work in urban schools and a new direction for research to address the mental health needs of immigrant Latino families. Through these examples we illustrate how DI can expand its reach by embedding within natural settings to build on local capacity and indigenous resources, incorporating the local knowledge necessary to more substantively address long-standing mental health disparities. This paradigm shift for DI, away from an overemphasis on promoting program adoption, calls for fitting interventions within settings that matter most to children's healthy development and for utilizing and strengthening available community resources. In this way, we can meet the challenge of addressing our nation's mental health burden by supporting the needs and values of families and communities within their own unique social ecologies. PMID- 26155974 TI - Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants. AB - Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers. PMID- 26155975 TI - Phase I/II trial of neoadjuvant sunitinib administered with weekly paclitaxel/carboplatin in patients with locally advanced triple-negative breast cancer. AB - The purpose of the study is to evaluate the feasibility and efficacy of adding sunitinib to paclitaxel/carboplatin in the neoadjuvant therapy of patients with triple-negative breast cancer (TNBC). Patients had histologically proven, previously untreated, triple-negative adenocarcinoma, with disease limited to the breast and axilla (clinical T1-T3, N0-N2, M0; T1N1M0 excluded). Following determination of the maximum tolerated doses in the phase I portion, patients in the phase II study received paclitaxel 70 mg/m(2) IV days 1, 8, and 15; carboplatin AUC 5.0 IV day 1; sunitinib 25 mg orally daily; treatment was administered for six 28-day cycles followed by definitive surgery. Sunitinib was resumed postoperatively to complete a 52-week course. Pathologic complete response (pCR) rate was the primary endpoint. Fifty-four patients enrolled; 41 received treatment in the phase II study. Sixteen patients (39 %) were able to complete six cycles of neoadjuvant therapy; 18 additional patients had surgery after completing 2-5 cycles of treatment. The pCR rate in these 34 evaluable patients was 35 %. The toxicity of the regimen was considerable, with myelosuppression resulting in numerous dose reductions and/or omissions of paclitaxel and carboplatin. Eleven patients (27 %) discontinued sunitinib during neoadjuvant therapy, and six patients (14 %) completed 52 weeks of single-agent sunitinib. In the neoadjuvant treatment of patients with TNBC, the combination of paclitaxel, carboplatin, and sunitinib was difficult to administer, and produced a pCR rate comparable to other less toxic regimens. This combination is not recommended for further evaluation. At present, sunitinib has no defined role in the treatment of breast cancer. PMID- 26155976 TI - Biodegradable fibre scaffolds incorporating water-soluble drugs and proteins. AB - A new type of biodegradable drug-loaded fibre scaffold has been successfully produced for the benefit of water-soluble drugs and proteins. Model drug loaded calcium carbonate (CaCO3) microparticles incorporated into poly(lactic acid-co glycolic acid) (PLGA) fibres were manufactured by co-precipitation of CaCO3 and the drug molecules, followed by electrospinning of a suspension of such drug loaded microparticles in a PLGA solution. Rhodamine 6G and bovine serum albumin were used as model drugs for our release study, representing small bioactive molecules and protein, respectively. A bead and string structure of fibres was achieved. The drug release was investigated with different drug loadings and in different pH release mediums. Results showed that a slow and sustained drug release was achieved in 40 days and the CaCO3 microparticles used as the second barrier restrained the initial burst release. PMID- 26155977 TI - The grafting of a thin layer of poly(sodium styrene sulfonate) onto poly(epsilon caprolactone) surface can enhance fibroblast behavior. AB - Poly(sodium styrene sulfonate) (pNaSS) was grafted onto poly(epsilon-caprolatone) (PCL) surfaces via ozonation and graft polymerization. The effect of ozonation and polymerization time, as well as the Mohr's salt concentration in the grafting solution, on the degree of grafting was investigated. The degree of grafting was determined through toluidine blue staining. The surface chemical change was characterized by attenuated total reflection Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The result demonstrated that the grafting did not induce any degradation of PCL, and that pNaSS was grafted onto PCL as a thin and covalently stable layer. Furthermore, the modified PCL surface reveals a significant increase in the metabolic activity of fibroblastic cells, as well as a better cell spreading with higher adhesion strength. Consequently, bioactivity of PCL is greatly enhanced by immobilizing a thin layer of pNaSS onto its surface. The grafting of pNaSS is a promising approach to increase the bioactivity of PCL based materials used in tissue engineering applications, such as ligament reconstruction. PMID- 26155978 TI - Control of oxygen release from peroxides using polymers. AB - An important limitation in cell therapy for the regeneration of tissue is the initial lack of oxygen. After implantation of large 3D cell-seeded structures, cells die rather than contribute to tissue regenerating. Here we've tested oxygen releasing materials to improve cell survival and growth after implantation. Calcium peroxide (CaO2) in a polymer matrix was used as source of oxygen. Two polymers were tested in order to slow down and extend the period of oxygen release, poly(D,L-lactic acid) and poly(lactic-co-glycolic acid). Compared to CaO2 particles, both releasing systems showed an initially higher and shorter oxygen release. Human mesenchymal stromal cells cultured on casted films of these oxygen-releasing composites required catalase to proliferate, indicating the production of cytotoxic hydrogen peroxide as intermediate. Poly(D,L-lactic acid) and poly(lactic-co-glycolic acid) are less suited for slowly oxygen-releasing materials. Catalase was able to reduce the cytotoxic effect of H2O2. PMID- 26155979 TI - Scientific Integrity and the Importance of a Clear Methodological Presentation in the Journal of Gerontological Social Work. PMID- 26155980 TI - The Use of Polystyrene Beads to Prepare Arrayed Samples of Bacillus thuringiensis for Microscopic Examination. AB - A common activity in the global search for useful Cry toxins is the microscopic screening of bacterial colonies for the presence of Bacillus thuringiensis. High throughput screens require that aliquots from large numbers of colonies be arrayed on a microscopic slide. However, precisely placing a small amount of bacteria on a slide, and at a density that is useful for microscopic examination, is both difficult to achieve and time consuming. Herein we share a simple technique that utilizes a hooked wand and small polystyrene beads to quickly collect, and uniformly apply, aliquots of bacterial colonies onto gridded microscope slides in a manner optimal for viewing. If desired, libraries of examined bacteria can simultaneously be generated by discharging the beads into indexed multiwell plates. This simple and inexpensive method is robust, suitable for both light and phase contrast microscopy, and has been also used successfully to screen randomly mutated bacteria for phenotypic changes. PMID- 26155981 TI - Protection of mice against Staphylococcus aureus infection by a recombinant protein ClfA-IsdB-Hlg as a vaccine candidate. AB - Staphylococcus aureus is one of the most important causes of nosocomial infections. An effective vaccine to prevent S. aureus infections is urgently required due to the dramatic increase in the number of antibiotic-resistant strains. In this report, we evaluated a newly recombinant protein composed of selected antigenic regions of clumping factor A (ClfA), iron surface determinant B (IsdB) and gamma hemolysin B (HlgB) of S. aureus and sequence coding for hydrophobic linkers between three domains. The recombinant gene was constructed in pET-28a (+) and expressed in Escherichia coli BL21. In addition, sequence coding for a His(6)-tag was added followed by a hybrid procedure of nickel chelate protein purification. Immunization of BALB/c mice with the recombinant protein ClfA-IsdB-Hlg evoked antigen-specific antibodies that could opsonize S. aureus cells, enhancing in vitro phagocytosis by macrophages. Vaccination with the recombinant protein also reduced the bacterial load recovered from mice spleen samples and increased survival following the intraperitoneal challenge with pathogenic S. aureus compared to the control mice. Our results showed that the recombinant protein ClfA-IsdB-Hlg is a promising vaccine candidate for the prevention of S. aureus bacteremia infections. PMID- 26155982 TI - Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study. AB - Co-infection with CMV in HIV-positive pregnant women is associated with perinatal mother-to-child transmission (MTCT) of both viruses. This retrospective study reports on the incidence of maternal and neonatal CMV (presence of anti-CMV IgG and IgM, CMV DNA PCR and/or CMV virus isolation) in high-risk pregnancies due to maternal HIV infection, MTCT of HIV and/or CMV. One hundred and eleven maternal samples and 75 matched neonatal samples were available for HIV and subsequent CMV testing. In this cohort of HIV-positive pregnant women, 96 (86.5 %) serum samples were anti-CMV IgG positive. In nine (9.4 %) of these, anti-CMV IgM was detected, and in none of them a maternal primary CMV infection was suspected. Fifty-seven (51.8 %) maternal serum samples were tested retrospectively by CMV DNA PCR; one sample was positive (0.9 %). All matched neonates were tested for HIV by PCR in the first month of life; HIV transmission was detected in one case. In 74 (67.2 %) of neonates, CMV testing was performed. Sixty-six of these serum samples were tested retrospectively by CMV DNA PCR. Two newborns (2.7 %) showed laboratory markers for CMV infection (one by detection of CMV DNA in plasma, and one by isolation of CMV from a urine sample). In the follow-up, neither of these two showed clinical signs for active CMV disease. We discussed these findings in the light of the national official guidelines. All CMV transmissions occurred due to maternal reinfection or endogenous reactivation. This suggests the success of highly active antiretroviral therapy in preventing MTCT of HIV and CMV disease and highlights the importance of adequate care and follow-up. PMID- 26155983 TI - Fetal magnetic resonance imaging: exposure times and functional outcomes at preschool age. AB - BACKGROUND: Fetal magnetic resonance imaging (MRI) has been routinely used as a noninvasive diagnostic tool for more than a decade; however, there is a paucity of follow-up studies examining the effects of prenatal exposure to 1.5-T MRI on developmental outcome. OBJECTIVE: The objective of this study was to assess the safety of 1.5-T fetal MRI by evaluating functional outcomes of preschool children who were exposed in utero. MATERIALS AND METHODS: In the context of a prospective observational study, healthy pregnant women underwent a 1.5-T MRI study using single-shot fast spin echo (SSFSE) sequences during the second or third trimester of pregnancy. The study was approved by the institutional review board at our institution, and written informed consent was obtained from all study participants. MRI scanning times were recorded, and prenatal/postnatal clinical data were collected prospectively. Functional outcomes were assessed using the Vineland Adaptive Behavior Scale (VABS), a widely used, norm-referenced and psychometrically sound functional assessment. RESULTS: We studied 72 healthy pregnant women, who underwent fetal MRI at a mean gestational age of 30.5 +/- 3.1 weeks. The cohort of fetuses was composed of 43% females, and 18 fetuses were scanned during the second trimester. All fetuses were born at term with appropriate birth weights (3.54 +/- 0.5 kg) for gestational age. Mean age at follow-up testing was 24.5 +/- 6.7 months. All children had age-appropriate scores in the communication, daily living, socialization and motor skills subdomains of the VABS (z-scores, P > 0.05). Furthermore, all children passed their newborn otoacoustic emission test and had normal hearing at preschool age. MRI study duration and exposure time to radio frequency waves and SSFSE sequences were not associated with adverse functional outcomes or hearing impairment. CONCLUSION: Prenatal exposure to 1.5-T MRI during the second or third trimester of pregnancy in a cohort of healthy fetuses is not associated with disturbances in functional outcomes or hearing impairment at preschool age. PMID- 26155984 TI - Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT). AB - The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin. Whole-body F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) was performed to identify a focus of infection. It demonstrated an unusual aspect of the thymus, which led to further investigation and revealed isolated infiltration of the thymus by Langerhans cell histiocytosis. The patient was treated accordingly and is now disease free. As evaluation of Langerhans cell histiocytosis patients with F-18 FDG PET/CT is becoming more frequent, it is important to be aware of the scintigraphical characteristics of thymic Langerhans cell histiocytosis. PMID- 26155986 TI - Normocalcemic primary hyperparathyroidism: a survey in a small village of Southern Italy. AB - We investigated the prevalence of normocalcemic primary hyperparathyroidism (NPHPT) in the adult population living in a village in Southern Italy. All residents in 2010 (n=2045) were invited by calls and 1046 individuals accepted to participate. Medical history, calcium intake, calcium, albumin, creatinine, parathyroid hormone (PTH) and 25OHD were evaluated. NPHPT was defined by normal albumin-adjusted serum calcium, elevated plasma PTH, and exclusion of common causes of secondary hyperparathyroidism (SHPT) (serum 25OHD <30 ng/ml, estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m(2) and thiazide diuretics use), overt gastrointestinal and metabolic bone diseases. Complete data were available for 685 of 1046 subjects. Twenty subjects did not meet the inclusion criteria and 341 could not be evaluated because of thawing of plasma samples. Classical PHPT was diagnosed in four women (0.58%). For diagnosing NPHPT the upper normal limit of PTH was established in the sample of the population (n=100) who had 25OHD >=30 ng/ml and eGFR >=60 ml/min per 1.73 m(2) and was set at the mean+3s.d. Three males (0.44%) met the diagnostic criteria of NPHPT. These subjects were younger and with lower BMI than those with classical PHPT. Our data suggest, in line with previous studies, that NPHPT might be a distinct clinical entity, being either an early phenotype of asymptomatic PHPT or a distinct variant of it. However, we cannot exclude that NPHPT might also represent an early phase of non-classical SHPT, since other variables, in addition to those currently taken into account for the diagnosis of NPHPT, might cumulate in a normocalcemic subject to increase PTH secretion. PMID- 26155987 TI - Relationships between beak condition, preening behavior and ectoparasite infestation levels in laying hens. AB - The effects of beak condition on ectoparasite populations and preening in laying hens were investigated. Beak-trimmed and beak-intact caged Hy-Line W-36 hens were infested with either chicken body lice or northern fowl mites using a 2*2 factorial design with 4 replicate cages (each containing 2 hens)/treatment: 1) BTL: (beak-trimmed lice-infested); 2) BTM: (beak-trimmed mite-infested); 3) BIL: (beak-intact lice-infested); and 4) BIM: (beak-intact mite-infested). Mite scores and lice numbers were estimated weekly. Hens were video recorded the wk before infestation and at wk 6 and 9 post-infestation. Time spent preening on 6 body areas and in total were analyzed using a repeated measures ANOVA. There was a wk*beak condition interaction for lice loads, with BTL harboring approximately 17 times more lice than BIL from wk 7 to 10 post-infestation (P<0.0001). Beak condition affected mite loads (P<0.0001), with BTM having a higher mite score (3.8+/-0.26) than BIM (1.4+/-0.26). At peak infestation, BTL spent more total time preening (P=0.02, s+/-SE: 232.1+/-37.6) than prior to infestation (33.9+/ 37.6) and directed their preening behavior towards the vent. In contrast, BIL (73.9+/-37.6), BTM (9.4+/-1.6), and BIM (8.6+/-1.6) did not increase total time spent preening over pre-infestation levels (103.6+/-37.6, 5.8+/-1.6, 6.7+/-1.6 respectively), although BTM did redirect their preening behavior toward the vent. This study confirmed previous studies showing that an intact beak is important for reducing ectoparasite infestations. Preening behavior increased in response to lice infestation, but only in beak-trimmed hens; preening behavior and louse load were correlated at peak infestation. In contrast, mite infestation did not lead to increased preening, and there was no correlation between preening and mite load. However, both lice- and mite-infested hens directed preening behavior predominantly towards the vent where these parasites are typically found. PMID- 26155988 TI - In-situ observation for growth of hierarchical metal-organic frameworks and their self-sequestering mechanism for gas storage. AB - Although structures with the single functional constructions and micropores were demonstrated to capture many different molecules such as carbon dioxide, methane, and hydrogen with high capacities at low temperatures, their feeble interactions still limit practical applications at room temperature. Herein, we report in-situ growth observation of hierarchical pores in pomegranate metal-organic frameworks (pmg-MOFs) and their self-sequestering storage mechanism, not observed for pristine MOFs. Direct observation of hierarchical pores inside the pmg-MOF was evident by in-situ growth X-ray measurements while self-sequestering storage mechanism was revealed by in-situ gas sorption X-ray analysis and molecular dynamics simulations. The results show that meso/macropores are created at the early stage of crystal growth and then enclosed by micropore crystalline shells, where hierarchical pores are networking under self-sequestering mechanism to give enhanced gas storage. This pmg-MOF gives higher CO2 (39%) and CH4 (14%) storage capacity than pristine MOF at room temperature, in addition to fast kinetics with robust capacity retention during gas sorption cycles, thus giving the clue to control dynamic behaviors of gas adsorption. PMID- 26155985 TI - Predicting Clearance Mechanism in Drug Discovery: Extended Clearance Classification System (ECCS). AB - Early prediction of clearance mechanisms allows for the rapid progression of drug discovery and development programs, and facilitates risk assessment of the pharmacokinetic variability associated with drug interactions and pharmacogenomics. Here we propose a scientific framework--Extended Clearance Classification System (ECCS)--which can be used to predict the predominant clearance mechanism (rate-determining process) based on physicochemical properties and passive membrane permeability. Compounds are classified as: Class 1A--metabolism as primary systemic clearance mechanism (high permeability acids/zwitterions with molecular weight (MW) <=400 Da), Class 1B--transporter mediated hepatic uptake as primary systemic clearance mechanism (high permeability acids/zwitterions with MW >400 Da), Class 2--metabolism as primary clearance mechanism (high permeability bases/neutrals), Class 3A--renal clearance (low permeability acids/zwitterions with MW <=400 Da), Class 3B--transporter mediated hepatic uptake or renal clearance (low permeability acids/zwitterions with MW >400 Da), and Class 4--renal clearance (low permeability bases/neutrals). The performance of the ECCS framework was validated using 307 compounds with single clearance mechanism contributing to >=70% of systemic clearance. The apparent permeability across clonal cell line of Madin - Darby canine kidney cells, selected for low endogenous efflux transporter expression, with a cut-off of 5 * 10(-6) cm/s was used for permeability classification, and the ionization (at pH7) was assigned based on calculated pKa. The proposed scheme correctly predicted the rate-determining clearance mechanism to be either metabolism, hepatic uptake or renal for ~92% of total compounds. We discuss the general characteristics of each ECCS class, as well as compare and contrast the framework with the biopharmaceutics classification system (BCS) and the biopharmaceutics drug disposition classification system (BDDCS). Collectively, the ECCS framework is valuable in early prediction of clearance mechanism and can aid in choosing the right preclinical tool kit and strategy for optimizing drug exposure and evaluating clinical risk of pharmacokinetic variability caused by drug interactions and pharmacogenomics. PMID- 26155989 TI - Menadione Sodium Bisulphite (MSB) enhances the resistance response of tomato, leading to repel mollusc pests. AB - BACKGROUND: Snails and slugs are terrestrial gastropods representing an important biotic stress that adversely affects crop yields. These pests are typically controlled with molluscicides, which produce pollution and toxicity and further induce the evolution of resistance mechanisms, making pest management even more challenging. In our work, we have assessed the efficacy of two different plant defence activators, menadione sodium bisulphite (MSB) and 1,2,3-benzothiadiazole 7-thiocarboxylic acid S-methyl ester (BTH), as inducers of resistance mechanisms of the model plant for defence, Solanum lycopersicum, against the generalist mollusc Theba grasseti (Helicidae). The study was designed to test the feeding behaviour and choice of snails, and also to analyse the expression profile of different genes specifically involved in defence against herbivores and wounds. RESULTS: Our data suggest that, through the downregulation of the terpene volatile genes and the production of proteinase inhibitors, treated MSB plants may be less apparent to herbivores that use herbivore-induced plant volatiles for host location. By contrast, BTH was not effective in the treatment of the pest, probably owing to an antagonistic effect derived from the induction of both salicylic-acid-dependent and jasmonic-acid-dependent pathways. CONCLUSIONS: This information is crucial to determine the genetic basis of the choice of terrestrial gastropod herbivores in tomato, providing valuable insight into how the plant defence activators could control herbivore pests in plants. Our work not only reports for the first time the interaction between tomato and a mollusc pest but also presents the action of two plant defence inductors that seems to produce opposed responses by inducing resistance mechanisms through different defence pathways. PMID- 26155990 TI - New Pacific trade deal--good for pharma, bad for public health? PMID- 26155991 TI - Occupational Exposure to Trichloramine and Trihalomethanes in Swedish Indoor Swimming Pools: Evaluation of Personal and Stationary Monitoring. AB - INTRODUCTION: Chlorination is a method commonly used to keep indoor swimming pool water free from pathogens. However, chlorination of swimming pools produces several potentially hazardous by-products as the chlorine reacts with nitrogen containing organic matter. Up till now, exposure assessments in indoor swimming pools have relied on stationary measurements at the poolside, used as a proxy for personal exposure. However, measurements at fixed locations are known to differ from personal exposure. METHODS: Eight public swimming pool facilities in four Swedish cities were included in this survey. Personal and stationary sampling was performed during day or evening shift. Samplers were placed at different fixed positions around the pool facilities, at ~1.5 m above the floor level and 0-1 m from the poolside. In total, 52 personal and 110 stationary samples of trichloramine and 51 personal and 109 stationary samples of trihalomethanes, were collected. RESULTS: The average concentration of trichloramine for personal sampling was 71 ug m(-3), ranging from 1 to 240 ug m(-3) and for stationary samples 179 ug m(-3), ranging from 1 to 640 ug m(-3). The air concentrations of chloroform were well below the occupational exposure limit (OEL). For the linear regression analysis and prediction of personal exposure to trichloramine from stationary sampling, only data from personal that spent >50% of their workday in the pool area were included. The linear regression analysis showed a correlation coefficient (r2) of 0.693 and a significant regression coefficient beta of 0.621; (95% CI = 0.329-0.912, P = 0.001). CONCLUSION: The trichloramine exposure levels determined in this study were well below the recommended air concentration level of 500 ug m(-3); a WHO reference value based on stationary sampling. Our regression data suggest a relation between personal exposure and area sampling of 1:2, implying an OEL of 250 ug m(-3) based on personal sampling. PMID- 26155992 TI - Genetic profiles of cervical tumors by high-throughput sequencing for personalized medical care. AB - Cancer treatment is facing major evolution since the advent of targeted therapies. Building genetic profiles could predict sensitivity or resistance to these therapies and highlight disease-specific abnormalities, supporting personalized patient care. In the context of biomedical research and clinical diagnosis, our laboratory has developed an oncogenic panel comprised of 226 genes and a dedicated bioinformatic pipeline to explore somatic mutations in cervical carcinomas, using high-throughput sequencing. Twenty-nine tumors were sequenced for exons within 226 genes. The automated pipeline used includes a database and a filtration system dedicated to identifying mutations of interest and excluding false positive and germline mutations. One-hundred and seventy-six total mutational events were found among the 29 tumors. Our cervical tumor mutational landscape shows that most mutations are found in PIK3CA (E545K, E542K) and KRAS (G12D, G13D) and others in FBXW7 (R465C, R505G, R479Q). Mutations have also been found in ALK (V1149L, A1266T) and EGFR (T259M). These results showed that 48% of patients display at least one deleterious mutation in genes that have been already targeted by the Food and Drug Administration approved therapies. Considering deleterious mutations, 59% of patients could be eligible for clinical trials. Sequencing hundreds of genes in a clinical context has become feasible, in terms of time and cost. In the near future, such an analysis could be a part of a battery of examinations along the diagnosis and treatment of cancer, helping to detect sensitivity or resistance to targeted therapies and allow advancements towards personalized oncology. PMID- 26155993 TI - The anti-inflammatory effect of calcium for preventing endothelial cell activation in preeclampsia. AB - Preeclampsia is a disorder of pregnancy characterized by endothelial activation. It is believed to be a response to a 'toxin(s)' from the placenta including trophoblastic debris and inflammatory cytokines. Calcium is known to reduce the risk of preeclampsia but the mechanism of its protective effect remains unknown. In this study, we investigated the potential mechanism(s) of calcium supplementation for preventing endothelial activation induced by trophoblastic debris. Trophoblastic debris was harvested from preeclamptic placentae and also from first-trimester placentae, which had been treated with preeclamptic sera. Endothelial cells were then cultured with trophoblastic debris in the presence of calcium. Endothelial activation was measured by quantifying endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) and by U937 monocyte adhesion to endothelial cells. The expression of ICAM-1 and U937 adhesion to endothelial cells were significantly reduced following exposure of endothelial cells to trophoblastic debris from preeclamptic placenta or from first-trimester placentae treated with preeclamptic sera in the presence of calcium compared with treatment without calcium. The expression of ICAM-1 was also significantly reduced following exposure of endothelial cells to trophoblastic debris with the nitric oxide donor or following treatment of endothelial cells with interleukin (IL) 1beta in the presence of calcium. Our study demonstrated that calcium supplementation prevented endothelial cell activation induced by trophoblastic debris from preeclamptic placentae. The nitric oxide synthase (NOS) pathway and anti-inflammatory effects are involved in the action of calcium on endothelial cell activation. These findings may suggest, at least in part, the protective mechanism of calcium supplementation on preeclampsia. PMID- 26155994 TI - Renal denervation for treatment of uncontrolled hypertension in an Asian population: results from the Global SYMPLICITY Registry in South Korea (GSR Korea). AB - Reports detailing the response of hypertensive patients to renal denervation (RDN) in Asian patients are limited. We evaluated 6- and 12-month outcomes after RDN in an Asian population and compared outcomes to a primarily Caucasian population. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, worldwide registry that evaluates the safety and effectiveness of RDN and includes the Korean registry substudy (GSR Korea) and a Caucasian subset (GSR Caucasian). Given differences in baseline characteristics among GSR Korea (n=93) as compared with GSR Caucasian (n=169) patients, including lower baseline office systolic blood pressure (SBP), lower body mass index and differences in medications, propensity score adjustment was performed when comparing the change in SBP between subsets. The 6- and 12-month change in SBP in GSR Korea was 19.4+/-17.2 and -27.2+/-18.1 mm Hg, respectively (P<0.001 for both vs baseline). GSR Caucasian had a SBP change similar to GSR Korea at 6 months (-20.9+/-21.4 mm Hg, unadjusted P=0.547, adjusted P=0.998), whereas at 12 months the change was significantly less pronounced (-20.1+/-23.9 mm Hg, unadjusted P=0.004, adjusted P=0.002). There were no protocol-defined procedure-related adverse events and no chronic adverse events associated with the device in an Asian population. RDN provided a significant reduction in 6- and 12-month office SBP among Asian patients, with a favorable safety profile. The 12-month SBP reduction was larger than that observed in Caucasian patients. PMID- 26155995 TI - Transcendental meditation and blood pressure. PMID- 26155997 TI - Structural and cosmetic outcomes of medial epicanthoplasty: An outcome study of three different techniques. AB - AIM: The authors intended to evaluate the structural and cosmetic outcomes of medial epicanthoplasty. METHODS: Medical records and photographs of 92 eyes from 46 Korean patients who underwent medial epicanthoplasty were reviewed retrospectively. The patients underwent epicanthoplasty using root Z-plasty, Y-V plasty, Mustarde's technique, and modified one-armed Mustarde's technique, from January 2009 to August 2011. Postoperative changes in the horizontal fissure width were measured for the assessment of structural outcome. The cosmetic outcomes were assessed in terms of appearance, symmetry, and scarring using a three-point grading system. Postoperative outcomes were evaluated at 1, 3, and 6 months after surgery. RESULTS: Root Z-plasty, Y-V plasty, and Mustarde's method (including Mustarde's technique and modified one-armed Mustarde's technique combined) with medial canthopexy were performed on 64, 13, and 15 eyes, respectively. Six months after surgery, the horizontal fissure width increased by an average of 1.74 (8.4%), 1.64 (8.9%), and 1.89 mm (12.9%), respectively (p < 0.001, 0.041, and 0.027). In addition, root Z-plasty had a higher postoperative appearance grade than Y-V plasty and Mustarde's method (p < 0.001). Grades of symmetry were good for all methods, and grades of scarring were good for root Z plasty and fair for the others. Scarring was significantly improved until postoperative 6 months in root Z-plasty and Y-V plasty (p < 0.001 and p = 0.022, respectively). CONCLUSIONS: Medial epicanthoplasty increased the horizontal fissure width of about 1.7 mm. Most cosmetic outcomes were satisfactory, with root Z-plasty resulting in excellent outcomes. Scarring faded over time. PMID- 26155996 TI - Hyperhomocysteinemia independently associated with the risk of hypertension: a cross-sectional study from rural China. AB - This study was designed to investigate the current prevalence of hyperhomocysteinemia (Hhcy) and its association with hypertension in rural adults of Northeast China. A cross-sectional study was performed in subjects aged?35 years in a general Chinese population. Demographic data, laboratory examination of traditional cardiovascular risk factors and self-reported information on lifestyle factors, such as physical activities, current smoking and drinking status, dietary habits and familial factors were collected by trained personnel. A total of 7130 participants (3317 men and 3813 women) were included in this study and the mean Hhcy level of the whole population was 17.39+/-12.34 mmol l( 1), which was 20.99+/-14.83 mmol l(-1) in males and 14.19+/-8.51 mmol l(-1) in females, respectively. Prevalence of Hhcy in total population was 41.3%. Stratified by gender, the prevalence of Hhcy was higher in males than in females (59.0 vs 25.8%, P<0.05). After adjustment for conventional risk factors including age, salt intake, smoking, body mass index, diabetes, dyslipidemia, activity time and family history, multiple logistic regression analysis showed that Hhcy was independently associated with the risk of hypertension in males (odds ratio (OR)=1.501, 95% confidence interval (CI): 1.012-2.227; P<0.001), but not in females in this population (OR=1.182; 95% CI, 0.993-1.407; P=0.060). In conclusion, a high prevalence of Hhcy in the general adult population of rural northeast China was detected and Hhcy may be a risk factor for hypertension, particularly in males. PMID- 26155998 TI - Efficacy of Neutral pH Electrolyzed Water in Reducing Escherichia coli O157:H7 and Salmonella Typhimurium DT 104 on Fresh Produce Items using an Automated Washer at Simulated Food Service Conditions. AB - The objective of this study was to determine the efficacy of neutral pH electrolyzed (NEO) water (155 mg/L free chlorine, pH 7.5) in reducing Escherichia coli O157:H7 and Salmonella Typhimurium DT 104 on romaine lettuce, iceberg lettuce, and tomatoes washed in an automated produce washer for different times and washing speeds. Tomatoes and lettuce leaves were spot inoculated with 100 MUL of a 5 strain cocktail mixture of either pathogen and washed with 10 or 8 L of NEO water, respectively. Washing lettuce for 30 min at 65 rpm led to the greatest reductions, with 4.2 and 5.9 log CFU/g reductions achieved for E. coli O157:H7 and S. Typhimurium respectively on romaine, whereas iceberg lettuce reductions were 3.2 and 4.6 log CFU/g for E. coli O157:H7 and S. Typhimurium respectively. Washing tomatoes for 10 min at 65 rpm achieved reductions greater than 8 and 6 log CFU/tomato on S. Typhimurium and E. coli O157:H7 respectively. All pathogens were completely inactivated in NEO water wash solutions. No detrimental effects on the visual quality of the produce studied were observed under all treatment conditions. Results show the adoption of this washing procedure in food service operations could be useful in ensuring produce safety. PMID- 26155999 TI - Acute Myocardial Infarction That Resulted From Poor Adherence to Medical Treatment for Giant Coronary Aneurysm. AB - Coronary arterial complications associated with Kawasaki disease (KD), such as a giant coronary aneurysm, determine the relative risk of future cardiac events and require lifelong medical treatment. Here, we describe a 24-year-old man who developed myocardial infarction due to poor adherence to medical treatment for a giant coronary aneurysm in the chronic phase of KD. He was hospitalized two hours after the onset of chest pain. The presence of the giant coronary aneurysm made primary percutaneous coronary intervention (PCI) difficult. However, we were able to perform primary PCI successfully utilizing previous coronary computed tomography (CT) angiographic pictures as a reference. This case provides valuable insight for the management of coronary arterial complications associated with KD. Patients in the chronic phase of KD are usually asymptomatic, even in the presence of giant coronary aneurysms which have been reported to have a high risk of morbidity and mortality. Therefore, patient education is critical for preventing poor adherence to medical treatment for coronary arterial complications. In preparation for potential coronary intervention in the future, it is also useful to perform coronary CT angiography, coronary magnetic resonance (MR) angiography, and/or coronary angiography on a regular basis while patients remain free from serious cardiac events. PMID- 26156000 TI - A High Throughput Ambient Mass Spectrometric Approach to Species Identification and Classification from Chemical Fingerprint Signatures. AB - A high throughput method for species identification and classification through chemometric processing of direct analysis in real time (DART) mass spectrometry derived fingerprint signatures has been developed. The method entails introduction of samples to the open air space between the DART ion source and the mass spectrometer inlet, with the entire observed mass spectral fingerprint subjected to unsupervised hierarchical clustering processing. A range of both polar and non-polar chemotypes are instantaneously detected. The result is identification and species level classification based on the entire DART-MS spectrum. Here, we illustrate how the method can be used to: (1) distinguish between endangered woods regulated by the Convention for the International Trade of Endangered Flora and Fauna (CITES) treaty; (2) assess the origin and by extension the properties of biodiesel feedstocks; (3) determine insect species from analysis of puparial casings; (4) distinguish between psychoactive plants products; and (5) differentiate between Eucalyptus species. An advantage of the hierarchical clustering approach to processing of the DART-MS derived fingerprint is that it shows both similarities and differences between species based on their chemotypes. Furthermore, full knowledge of the identities of the constituents contained within the small molecule profile of analyzed samples is not required. PMID- 26156001 TI - Antibacterial property of Ag nanoparticle-impregnated N-doped titania films under visible light. AB - Photocatalysts produce free radicals upon receiving light energy; thus, they possess antibacterial properties. Silver (Ag) is an antibacterial material that disrupts bacterial physiology. Our previous study reported that the high antibacterial property of silver nanoparticles on the surfaces of visible light responsive nitrogen-doped TiO2 photocatalysts [TiO2(N)] could be further enhanced by visible light illumination. However, the major limitation of this Ag-TiO2 composite material is its durability; the antibacterial property decreased markedly after repeated use. To overcome this limitation, we developed TiO2(N)/Ag/TiO2(N) sandwich films in which the silver is embedded between two TiO2(N) layers. Various characteristics, including silver and nitrogen amounts, were examined in the composite materials. Various analyses, including electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and ultraviolet visible absorption spectrum and methylene blue degradation rate analyses, were performed. The antibacterial properties of the composite materials were investigated. Here we revealed that the antibacterial durability of these thin films is substantially improved in both the dark and visible light, by which bacteria, such as Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, and Acinetobacter baumannii, could be efficiently eliminated. This study demonstrated a feasible approach to improve the visible-light responsiveness and durability of antibacterial materials that contain silver nanoparticles impregnated in TiO2(N) films. PMID- 26156002 TI - The Role of Xylitol Gum Chewing in Restoring Postoperative Bowel Activity After Cesarean Section. AB - AIMS: The goal of this study was to evaluate the effects of xylitol gum chewing on gastrointestinal recovery after cesarean section. METHODS: Women who underwent cesarean section (N = 120) were randomly allocated into Group A (xylitol gum), Group B (nonxylitol gum), or the control group (no chewing gum). Every 2 hr post cesarean section and until first flatus, Groups A and B received two pellets of chewing gum and were asked to chew for 15 min. The times to first bowel sounds, first flatus, and first defecation were then compared among the three groups. RESULTS: Group A had the shortest mean time to first bowel sounds (6.9 +/- 1.7 hr), followed by Group B (8 +/- 1.6 hr) and the control group (12.8 +/- 2.5 hr; one-way analysis of variance, p < .001; Scheffe's post hoc comparisons, p < .05). The gum-chewing groups demonstrated a faster return of flatus than the control group did (p < .001), but the time to flatus did not differ significantly between the gum-chewing groups. Additionally, the differences in the time to first defecation were not significant. CONCLUSION: After cesarean section, chewing gum increased participants' return of bowel activity, as measured by the appearance of bowel sounds and the passage of flatus. In this context, xylitol-containing gum may be superior to xylitol-free gum. PMID- 26156003 TI - Serum Tryptophan Metabolite Levels During Sleep in Patients With and Without Irritable Bowel Syndrome (IBS). AB - Poor sleep and stress are more frequently reported by women with irritable bowel syndrome (IBS) than by healthy control (HC) women. The pathophysiology linking poor sleep and stress to gastrointestinal symptoms remains poorly understood. We used a metabolomic approach to determine whether tryptophan (TRP) metabolites differ between women with and without IBS and whether the levels are associated with sleep indices and serum cortisol levels. This study sample included 38 women with IBS and 21 HCs. The women were studied in a sleep laboratory for three consecutive nights. On the third night of the study, a social stressor was introduced, then blood samples were drawn every 20 min and sleep indices were measured. Metabolites were determined by targeted liquid chromatography tandem mass spectrometry in a sample collected 1 hr after the onset of sleep. The ratios of each metabolite to TRP were used for analyses. Correlations were controlled for age and oral contraceptive use. Melatonin/TRP levels were lower (p = .005) in the IBS-diarrhea group versus the IBS-constipation and HC groups, and kynurenine/TRP ratios tended to be lower (p = .067) in the total IBS and IBS diarrhea groups compared to HCs. Associations within the HC group included melatonin/TRP with polysomnography-sleep efficiency (r = .61, p = .006) and weaker positive correlations with the other ratios for either sleep efficiency or percentage time in rapid eye movement sleep (r > .40, p = .025-.091). This study suggests that reductions in early nighttime melatonin/TRP levels may be related to altered sleep quality in IBS, particularly those with diarrhea. PMID- 26156004 TI - A novel green-emitting phosphor Ba2Gd2Si4O13:Eu(2+) for near UV-pumped light emitting diodes. AB - A novel green-emitting phosphor Ba2Gd2Si4O13:Eu(2+) has been prepared using a conventional high-temperature solid-state method. X-ray diffraction and photoluminescence spectra were used to characterize the as-synthesized phosphor. The Ba2Gd2Si4O13:Eu(2+) phosphor exhibits a broad emission band centered at 503 nm under 365 nm excitation. Monitoring the 503 nm emission, the Ba2Gd2Si4O13:Eu(2+) phosphor shows an intense broad excitation band ranging from 200 to 410 nm. The concentration quenching mechanism has been investigated, and demonstrated to involve a dipole-dipole interaction. The critical concentration was found to be about 4 mol%. The critical distance calculated using the concentration method and spectral overlap method was 23.9 A and 27.1 A, respectively. The temperature-dependent photoluminescence and CIE chromaticity coordinate of the Ba2Gd2Si4O13:Eu(2+) phosphor were also investigated in this work. The results revealed that Ba2Gd2Si4O13:Eu(2+) possesses excellent thermal stability and the CIE value of the Ba2Gd2Si4O13:0.04 Eu(2+) phosphor upon 365 nm excitation is (0.211, 0.434), located in the green region. All the properties indicate that the Ba2Gd2Si4O13:Eu(2+) phosphor is a potential green-emitting phosphor fit for ultraviolet light pumped LEDs. PMID- 26156006 TI - Are we doing enough for our patients with terminal cancer? A moral imperative to step up palliative care practice in Sub-Saharan Africa. PMID- 26156005 TI - Preferred and actual place of death in haematological malignancy. AB - OBJECTIVES: Home is considered the preferred place of death for many, but patients with haematological malignancies (leukaemias, lymphomas and myeloma) die in hospital more often than those with other cancers and the reasons for this are not wholly understood. We examined preferred and actual place of death among people with these diseases. METHODS: The study is embedded within an established population-based cohort of patients with haematological malignancies. All patients diagnosed at two of the largest hospitals in the study area between May 2005 and April 2008 with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma, who died before May 2010 were included. Data were obtained from medical records and routine linkage to national death records. RESULTS: 323 deceased patients were included. A total of 142 (44%) had discussed their preferred place of death; 45.8% wanted to die at home, 28.2% in hospital, 16.9% in a hospice, 5.6% in a nursing home and 3.5% were undecided; 63.4% of these died in their preferred place. Compared to patients with evidence of a discussion, those without were twice as likely to have died within a month of diagnosis (14.8% vs 29.8%). Overall, 240 patients died in hospital; those without a discussion were significantly more likely to die in hospital than those who had (p<=0.0001). Of those dying in hospital, 90% and 75.8% received haematology clinical input in the 30 and 7 days before death, respectively, and 40.8% died in haematology areas. CONCLUSIONS: Many patients discussed their preferred place of death, but a substantial proportion did not and hospital deaths were common in this latter group. There is scope to improve practice, particularly among those dying soon after diagnosis. We found evidence that some people opted to die in hospital; the extent to which this compares with other cancers is of interest. PMID- 26156007 TI - Nutritional status and immune response in murine experimental Jorge Lobo's disease. AB - There are no studies investigating the role of nutritional status and immunity associated with Jorge Lobo's disease. The objective of this study was to evaluate the effects of protein-calorie malnutrition on the immune response of BALB/c mice inoculated with Lacazia loboi. In this study,the animals were divided into four groups: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. The animals of groups G1 and G2 were submitted to malnutrition for 20 days and once installed the animals were inoculated intradermally into the footpad. After 4 months, they were euthanised for the isolation of peritoneal lavage cells and removal of the footpad. The production of IL-2, IL-4, IL-10, IL-12, IFN-gamma, TNF-alpha, H2 O2 and nitric oxide (NO) was evaluated in the peritoneal lavage cells. The footpad was evaluated regarding the size of macroscopic lesions, number of fungi and viability index. The results showed that the infection did not exert great influence on the body weight of the mice and previous malnutrition was an unfavourable factor for viability index, number of fungi, macroscopic lesion size in the footpad and production of H2 O2 , NO, IL-12, IL-10 and IFN-gamma, suggesting that malnutrition significantly altered fungal activity and peritoneal cells. The results suggest considerable interaction between nutrition and immunity in Jorge Lobo's disease. PMID- 26156009 TI - Immunomodulation in host-protective immune response against murine tuberculosis through regulation of the T regulatory cell function. AB - Tuberculosis, caused by the bacteria Mycobacterium tuberculosis, is characterized by an infection in lung and spleen. In the present study, we have elucidated the mechanism by which Mycobacterium indicus pranii renders protection in in vivo Mycobacterium tuberculosis infection. We observed that Mycobacterium indicus pranii treated infected C57BL/6 mice showed a strong host-protective Th1 immune response along with a marked decrease in immunosuppressive cytokines, TGF-beta, and IL-10-secreting CD4(+) T cells. This Mycobacterium indicus pranii mediated decrease in immunosuppressive cytokines was correlated with the reduction in the elevated frequency of CD4(+)CD25(+) T regulatory cells, along with the reduced TGF-beta production from these T regulatory cells in tuberculosis-infected mice. This reduction in the T regulatory cell population was a result of effective modulation of STAT4-STAT5 transcription factor counter-regulation by Mycobacterium indicus pranii, which in turn, reduced the immunosuppressive activity of T regulatory cells. Thus, these findings put forward a detailed mechanistic insight into Mycobacterium indicus pranii mediated regulation of the T regulatory cell functioning during experimental murine tuberculosis, which might be helpful in combating Mycobacterium-induced pathogenesis. PMID- 26156008 TI - Tuberculous pleurisy drives marked effector responses of gammadelta, CD4+, and CD8+ T cell subpopulations in humans. AB - Although tuberculous pleurisy (TP) presumably involves a hypersensitivity reaction, there is limited evidence indicating overreactive effector responses of gammadelta T cells and alphabeta T cells and their interrelation with Foxp3(+) Tregs in pleural and other compartments. We found that TP induced reciprocal representations of Foxp3(+) Tregs and Mtb phosphoantigen-specific Vgamma2Vdelta2 T cells in different anatomic compartments. Patients with TP exhibited appreciable numbers of "proliferating" Ki-67(+) Vgamma2Vdelta2 T cells in the airway where Foxp3(+) Tregs were not dominant, whereas striking increases in Foxp3(+) Tregs in the blood and pleural compartments coincided with low frequencies of Vgamma2Vdelta2 T cells. Interestingly, anti-tuberculosis chemotherapy control of Mtb infection in patients with TP reversed reciprocal representations of Foxp3(+) Tregs and proliferating Vgamma2Vdelta2 T cells. Surprisingly, despite high-level Foxp3(+) Tregs, TP appeared to drive overreactive responses of IFN-gamma-producing Vgamma2Vdelta2, CD4(+)CD25(+), and CD8(+)CD25(+) T effector subpopulations, whereas IL-22-producing Vgamma2Vdelta2 T cells increased subtly. Th1 effector responses were sustained despite remarkable declines in Foxp3(+) Tregs at 1 mo after the treatment. Overreactive T effector responses of Mtb-reactive gammadelta T cells, alphabeta CD25(+)CD4(+), and CD25(+)CD8(+) T cell subpopulations appear to be immune features for TP. Increased Foxp3(+) Tregs might be responsive to overreactive TP but unable to influence T effector responses despite having an inverse relation with proliferating Vgamma2Vdelta2 T cells. PMID- 26156012 TI - Relationship between three novel SNPs of BRCA1 and canine mammary tumors. AB - The BRCA1 gene plays an important role in the development of human breast cancer, and recent research indicated that genetic variations of BRCA1 are also related to canine mammary tumors (CMTs). Here, using rapid amplification of cDNA ends (RACE), we cloned the 5'- and 3'-UTRs of BRCA1. By direct sequencing of the flanking sequences of the 5'- and 3'-UTRs of BRCA1, three previously unreported single-nucleotide polymorphisms (SNPs) were identified, two (-1228T >C, -1173C >T) in the putative promoter regions and one non-synonymous SNP (63449G >A) in exon 23. Compared with 16 normal samples, the sequences from 34 CMTs suggested that SNP (-1173C >T) was associated with the development of CMTs (odds ratio (OR)=2.57, 95% confidence interval (CI): 1.07-6.15). PMID- 26156013 TI - Pathogenicity of emerging Japanese type 1 porcine reproductive and respiratory syndrome virus in experimentally infected pigs. AB - To clarify the pathogenicity of Japanese type 1 porcine reproductive and respiratory syndrome virus (PRRSV) isolate in experimentally infected pigs, we evaluated clinical signs and monitored viremia for 21 days post-inoculation (dpi). Lungs were mottled, tanned and reddish in appearance; had lesions predominantly in the cranial, middle and accessory lobes; and failed to collapse at 10 dpi. Although microscopic lesions of lungs were reproduced using the Japanese emerging type 1 PRRSV isolate under experimental conditions, no significant differences were noted between the challenge and control groups regarding mean rectal temperature and daily weight gain. These results provide useful insights into the limited pathogenicity of single infection with the Japanese type 1 PRRSV isolate in piglets, which differ from findings in reported field cases. PMID- 26156015 TI - Comparison of 2-Dimensional, 3-Dimensional, and Surgical Measurements of the Tricuspid Annulus Size: Clinical Implications. AB - BACKGROUND: Associated tricuspid annuloplasty is recommended during left-heart valve surgery when the tricuspid annulus (TA) is dilated but methodology for the measurement of TA size and thresholds for TA enlargement are not clearly defined. METHODS AND RESULTS: Measurement of the TA diameter (TAD) was prospectively performed using 2-dimensional transthoracic echocardiography (2D-TTE) in 282 patients in 4 different views (parasternal long axis, parasternal short axis, apical 4-chamber [A4C], and subcostal). TAD was also measured using 3D transesophageal echocardiography in 183 patients (long axis), peroperatively in 120 patients who underwent a tricuspid valve surgery and using TTE (A4C) in 66 healthy volunteers. TAD was significantly different between the 4 2D-TTE views (3.85+/-0.58, 3.87+/-0.61, 4.02+/-0.69, and 3.92+/-0.65 cm, respectively; P<0.0001) but differences were small and the A4C was the most feasible (76%, 65%, 92%, and 73%, respectively; P<0.0001) and offered the highest reproducibility. TAD measured in A4C view was smaller than when measured by 3D-transesophageal echocardiography (3.90+/-0.63 versus 4.33+/-0.62 cm; P<0.0001) but correlation was excellent (r=0.84; P<0.0001) with a systematic 4-mm underestimation. In contrast, 2D-TTE measurements were significantly smaller and only modestly correlated to surgical measurements (4.11+/-0.61 versus 4.37+/-0.75 cm; P<0.0001; r=0.57; P<0.0001) which were poorly reproducible. In healthy volunteers, we suggested 42 mm or 23 mm/m(2) as pathological values for the TAD in A4C. CONCLUSIONS: Measurements of the TAD using 2D-TTE in A4C were highly feasible and reproducible and despite being systematically smaller than 3D measurements, accurately reflected the degree of TA enlargement as assessed using 3D transesophageal echocardiography. We proposed the thresholds that may be used in future prospective studies to demonstrate whether a preventive strategy would improve the outcome. PMID- 26156014 TI - Molecular Imaging of Platelet-Endothelial Interactions and Endothelial von Willebrand Factor in Early and Mid-Stage Atherosclerosis. AB - BACKGROUND: Nonthrombotic platelet-endothelial interactions may contribute to atherosclerotic plaque development, although in vivo studies examining mechanism without platelet preactivation are lacking. Using in vivo molecular imaging at various stages of atherosclerosis, we quantified platelet-endothelial interactions and evaluated the contribution of major adhesion pathways. METHODS AND RESULTS: Mice deficient for the low-density lipoprotein receptor and Apobec-1 were studied as an age-dependent model of atherosclerosis at 10, 20, 30, and 40 weeks of age, which provided progressive increase in stage from early fatty streak (10 weeks) to large complex plaques without rupture (40 weeks). Platelet targeted contrast ultrasound molecular imaging of the thoracic aorta performed with microbubbles targeted to GPIbalpha demonstrated selective signal enhancement as early as 10 weeks of age. This signal increased progressively with age (almost 8-fold increase from 10 to 40 weeks, analysis of variance P<0.001). Specificity for platelet targeting was confirmed by the reduction in platelet-targeted signal commensurate with the decrease in platelet count after immunodepletion with anti GPIb or anti-CD41 antibody. Inhibition of P-selectin in 20 and 40 weeks atherosclerotic mice resulted in a small (15% to 30%) reduction in platelet signal. Molecular imaging with microbubbles targeted to the A1 domain of von Willebrand factor demonstrated selective signal enhancement at all time points, which did not significantly increase with age. Treatment of 20 and 40 week mice with recombinant ADAMTS13 eliminated platelet and von Willebrand factor molecular imaging signal. CONCLUSIONS: Platelet-endothelial interactions occur in early atherosclerosis. These interactions are in part caused by endothelial von Willebrand factor large multimers, which can be reversed with exogenous ADAMTS13. PMID- 26156016 TI - Noninvasive Imaging of Atherosclerotic Plaque Progression: Status of Coronary Computed Tomography Angiography. AB - The process of coronary artery disease progression is infrequently visualized. Intravascular ultrasound has been used to gain important insights but is invasive and therefore limited to high-risk patients. For low-to-moderate risk patients, noninvasive methods may be useful to quantitatively monitor plaque progression or regression and to understand and personalize atherosclerosis therapy. This review discusses the potential for coronary computed tomography angiography to evaluate the extent and subtypes of coronary plaque. Computed tomographic technology is evolving and image quality of the method approaches the level required for plaque progression monitoring. Methods to quantify plaque on computed tomography angiography are reviewed as well as a discussion of their use in clinical trials. Limitations of coronary computed tomography angiography compared with competing modalities include limited evaluation of plaque subcomponents and incomplete knowledge of the value of the method especially in patients with low-to-moderate cardiovascular risk. PMID- 26156017 TI - Friend leukemia virus integration 1 activates the Rho GTPase pathway and is associated with metastasis in breast cancer. AB - Breast cancer is the most prevalent malignant disease in women worldwide. In patients with breast cancer, metastasis to distant sites directly determines the survival outcome. However, the molecular mechanism underlying metastasis in breast cancer remains to be defined. In this report, we found that Friend leukemia virus integration 1 (FLI1) proto-oncogene was differentially expressed between the aggressive MDA-MB231 and the non-aggressive MCF-7 breast cancer cells. Congruently, immunohistochemical staining of clinical samples revealed that FLI1 was overexpressed in breast cancers as compared with the adjacent tissues. The abundance of FLI1 protein was strongly correlated with the advanced stage, poor differentiation, and lymph node metastasis in breast cancer patients. Knockdown of FLI1 with small interfering RNAs significantly attenuated the potential of migration and invasion in highly metastatic human breast cancer cells. FLI1 oncoprotein activated the Rho GTPase pathway that is known to play a role in tumor metastasis. This study for the first time identifies FLI1 as a clinically and functionally important target gene of metastasis, providing a rationale for developing FLI1 inhibitors in the treatment of breast cancer. PMID- 26156018 TI - High copy number variation of cancer-related microRNA genes and frequent amplification of DICER1 and DROSHA in lung cancer. AB - A growing body of evidence indicates that miRNAs may be a class of genetic elements that can either drive or suppress oncogenesis. In this study we analyzed the somatic copy number variation of 14 miRNA genes frequently found to be either over- or underexpressed in lung cancer, as well as two miRNA biogenesis genes, DICER1 and DROSHA, in non-small-cell lung cancer (NSCLC). Our analysis showed that most analyzed miRNA genes undergo substantial copy number alteration in lung cancer. The most frequently amplified miRNA genes include the following: miR-30d, miR-21, miR-17 and miR-155. We also showed that both DICER1 and DROSHA are frequently amplified in NSCLC. The copy number variation of DICER1 and DROSHA correlates well with their expression and survival of NSCLC and other cancer patients. The increased expression of DROSHA and DICER1 decreases and increases the survival, respectively. In conclusion, our results show that copy number variation may be an important mechanism of upregulation/downregulation of miRNAs in cancer and suggest an oncogenic role for DROSHA. PMID- 26156019 TI - The endoplasmic reticulum mitochondrial calcium cross talk is downregulated in malignant pleural mesothelioma cells and plays a critical role in apoptosis inhibition. AB - The failure of apoptosis may contribute to the formation of cancer and to its resistance to therapy. Malignant pleural mesothelioma (MPM) is an aggressive tumor that responds poorly to standard chemo- and radio-therapies. Several studies have demonstrated that a plethora of oncogenes and tumor suppressors contribute to MPM onset/progression. Importantly, most of these genes are involved in the regulation of calcium (Ca2+)-handling. Cellular Ca2+ signaling is an important regulator of many physiological processes, and it has been widely reported to participate in the regulation of apoptotic cell death in cancer cells and tissues. However, in MPM the role of cellular Ca2+ has been poorly investigated. Therefore, we examined whether Ca2+ is involved in MPM. We found that mesothelioma cell lines and short-term cultures obtained from MPM-affected patients exhibited a critical dysregulation in Ca2+ signaling. We determined that this characteristic was associated with resistance to apoptotic stimuli and that correction of intracellular Ca2+ signaling resulted in the rescue of efficient apoptotic responses. In addition, we discovered that mitochondrial Ca2+-uptake plays a pivotal role as an inducer of apoptosis in MPM. Altogether, these findings suggest the identification of new MPM markers, which in turn could be potential targets for new therapeutic approaches. PMID- 26156020 TI - High expression of XPA confers poor prognosis for nasopharyngeal carcinoma patients treated with platinum-based chemoradiotherapy. AB - In this study, we tried to explore if xeroderma pigmentosum complementation group A (XPA) expression is likely a prognostic prediction factor for locally advanced nasopharyngeal carcinoma (NPC) patients treated with platinum-based chemoradiotherapy, which was considered to bring chemotherapy-related severe toxicity compared with radiotherapy alone. Firstly, MTT assay revealed that downregulating XPA expression in NPC HONE1 and CNE1 cells decreased IC50 of cisplatin and sensitized cells to cisplatin. XPA expression was detected by immunohistochemistry in cancer tissues from locally advanced NPC patients treated with platinum-based chemoradiotherapy. The relationships between XPA expression and clinicopathologic features, overall survival and progression-free survival of patients were evaluated. The results showed that XPA expression was not associated with clinicopathologic parameters, but was likely an independent prognostic factor for patient survival. High XPA level predicts a poor prognosis, and the prediction values were higher in subgroups of younger, higher EBV antibody titer, or treated with concurrent chemoradiotherapy. Combining XPA levels and T/N classifications, we successfully classified these patients into low, medium and high risk groups for platinum-based chemoradiotherapy. These findings suggest that XPA levels may be a potential predictor of prognosis in locally advanced NPC patients treated with platinum-based chemoradiotherapy, and helpful for selecting patients likely to need and benefit from this treatment in future. PMID- 26156021 TI - Are VEGFR-TKIs effective or safe for patients with advanced non-small cell lung cancer? AB - Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) might be new therapeutic strategies for advanced non-small cell lung cancer (NSCLC). Here a total of 12,520 patients from 23 randomized controlled trials (RCTs) were enrolled to evaluate the efficacy and safety of VEGFR-TKIs quantitatively in advanced NSCLC. Compared with non-VEGFR-TKIs, VEGFR-TKIs regimen significantly improved progression-free survival (PFS) [hazard ratio (HR): 0.839, 95% confidence interval (CI): 0.805-0.874, P < 0.001], objective response rates (ORR) [relative risk (RR): 1.374, 95%CI: 1.193-1.583, P < 0.001] and disease control rates (DCR) (RR: 1.113, 95%CI: 1.027-1.206, P =0.009), but not overall survival (OS) (HR: 0.960, 95%CI: 0.921-1.002, P =0.060) for NSCLC patients. The RR of all-grade neutropenia, thrombocytopenia, hypertension, hemorrhage, fatigue, anorexia, stomatitis, diarrhea, rash, hand-foot skin reaction (HFSR) were increased in patients received VEGFR-TKIs. As for high-grade (>=3) adverse events (AEs), VEGFR-TKIs were associated with higher RR of neutropenia, thrombocytopenia, hypertension, fatigue, stomatitis, diarrhea, rash and HFSR. This study demonstrates VEGFR-TKIs improve PFS, ORR and DCR, but not OS in advanced NSCLC patients. VEGFR-TKIs induce more frequent and serious AEs compared with control therapies. PMID- 26156022 TI - Excellent local control and survival after postoperative or definitive radiation therapy for sarcomas of the head and neck. AB - BACKGROUND: To report our results with postoperative or definitive radiation therapy in head and neck sarcomas. METHODS: We performed a retrospective analysis of 26 patients suffering from head and neck sarcomas, who received postoperative or definitive radiation therapy between 2003 and 2012. Median age was 64 years (19-88) and 69 % were male. Tumor locations were skull (including skin) in 31 %, paranasal sinus/orbita in 27 % and neck (including pharynx/larynx) in 42 %. Median tumor size was 4.6 cm (1-12 cm). 22 patients (85 %) presented in primary situation. Stage at presentation (UICC 7(th) for soft tissue sarcomas) was as follows: Ia:4 %, IIa:50 %, IIb:15 %, III:31 %. All except one patient suffered from high grade lesions (G2/3 FNCLCC), predominantly angiosarcoma (35 %), MFH (19 %) and synovial sarcoma (15 %). Surgery was performed in 21 pts (81 %), resulting in free margins in 10 (38 %), microscopically positive margins in 6 (23 %) and gross residual disease in 5 (19 %). Median dose to the primary tumor region was 66Gy (45-72Gy) in conventional fractionation, using 3D-CRT in 65 %, IMRT in 27 % and electrons in 8 %. 50 % of the patients also received sequential chemotherapy. RESULTS: Median follow up was 39 months (8-136). We observed three local recurrences, transferring into estimated 3- and 5-year local control rates of 86 %. One additional patient failed distantly, resulting in 3- and 5-year freedom from treatment failure rates of 82 %. Four patients have deceased, transferring into 3- and 5-year overall survival rates of 88 % and 82 %, respectively. Only two of the four deaths were sarcoma related. Maximum acute toxicity (CTCAE 3.0) was grade 1 in 27 % of the patients, grade 2 in 50 % and grade 3 in 23 %. Severe acute toxicity was mainly represented by mucositis and dysphagia. Maximum late toxicity was grade 1 in 31 %, grade 2 in 15 % and grade 3 in 19 % of the patients. Severe late toxicity included skin ulceration (n = 1), dysphagia with persistent tube dependency (n = 1), persistent sinusitis (n = 1) and hearing loss (n = 2). CONCLUSION: Excellent local control and overall survival rates can be achieved with postoperative or definitive radiation therapy with acceptable acute and late toxicities in patients suffering from sarcomas of the head and neck region. PMID- 26156023 TI - The Interplay of Disulfide Bonds, alpha-Helicity, and Hydrophobic Interactions Leads to Ultrahigh Proteolytic Stability of Peptides. AB - The contribution of noncovalent interactions to the stability of naturally occurring peptides and proteins has been generally acknowledged, though how these can be rationally manipulated to improve the proteolytic stability of synthetic peptides remains to be explored. In this study, a platform to enhance the proteolytic stability of peptides was developed by controllably dimerizing them into alpha-helical dimers, connected by two disulfide bonds. This platform not only directs peptides toward an alpha-helical conformation but permits control of the interfacial hydrophobic interactions between the peptides of the dimer. Using two model dimeric systems constructed from the N-terminal alpha-helix of RNase A and known inhibitors for the E3 ubiquitin ligase MDM2 (and its homologue MDMX), a deeper understanding into the interplay of disulfide bonds, alpha-helicity, and hydrophobic interactions on enhanced proteolytic stability was sought out. Results reveal that all three parameters play an important role on attaining ultrahigh proteolytic resistance, a concept that can be exploited for the development of future peptide therapeutics. The understanding gained through this study will enable this strategy to be tailored to new peptides because the proposed strategy displays substantial tolerance to sequence permutation. It thus appears promising for conveniently creating prodrugs composed entirely of the therapeutic peptide itself (i.e., in the form of a dimer). PMID- 26156026 TI - Possibilities for a Composite Approach: Summary of the Disaster Gerontology Panel at the International College of Geriatric Psychoneuropharmacology Annual Meeting (ICGP-2014). PMID- 26156027 TI - Fifty years of fat: news coverage of trends that predate obesity prevalence. AB - BACKGROUND: Obesity prevalence has risen in fifty years. While people generally expect media mentions of health risks like obesity prevalence to follow health risk trends, food consumption trends may precede obesity prevalence trends. Therefore, this research investigates whether media mentions of food predate obesity prevalence. METHODS: Fifty years of non-advertising articles in the New York Times (and 17 years for the London Times) are coded for the mention of less healthy (5 salty and 5 sweet snacks) and healthy (5 fruits and 5 vegetables) food items by year and then associated with annual obesity prevalence in subsequent years. Time-series generalized linear models test whether food-related mentions predate or postdate obesity prevalence in each country. RESULTS: United States obesity prevalence is positively associated with New York Times mentions of sweet snacks (b = 55.2, CI = 42.4 to 68.1, p = .000) and negatively associated with mentions of fruits (b = -71.28, CI -91.5 to -51.1, p = .000) and vegetables (b = 13.6, CI = -17.5 to -9.6, p = .000). Similar results are found for the United Kingdom and The London Times. Importantly, the "obesity followed mentions" models are stronger than the "obesity preceded mentions" models. CONCLUSIONS: It may be possible to estimate a nation's future obesity prevalence (e.g., three years from now) based on how frequently national media mention sweet snacks (positively related) and vegetables or fruits (negatively related) today. This may provide public health officials and epidemiologists with new tools to more quickly assess the effectiveness of current obesity interventions based on what is mentioned in the media today. PMID- 26156024 TI - Serological profile of foot-and-mouth disease in wildlife populations of West and Central Africa with special reference to Syncerus caffer subspecies. AB - The role which West and Central African wildlife populations might play in the transmission dynamics of FMD is not known nor have studies been performed in order to assess the distribution and prevalence of FMD in wild animal species inhabiting those specific regions of Africa. This study reports the FMD serological profile extracted from samples (n = 696) collected from wildlife of West and Central Africa between 1999 and 2003. An overall prevalence of FMDV NSP reactive sera of 31.0% (216/696) was estimated, where a significant difference in seropositivity (p = 0.000) was reported for buffalo (64.8%) as opposed to other wild animal species tested (17.8%). Different levels of exposure to the FMDV resulted for each of the buffalo subspecies sampled (p = 0.031): 68.4%, 50.0% and 0% for Nile Buffalo, West African Buffalo and African Forest Buffalo, respectively. The characterisation of the FMDV serotypes tested for buffalo found presence of antibodies against all the six FMDV serotypes tested, although high estimates for type O and SAT 3 were reported for Central Africa. Different patterns of reaction to the six FMDV serotypes tested were recorded, from sera only positive for a single serotype to multiple reactivities. The results confirmed that FMDV circulates in wild ruminants populating both West and Central Africa rangelands and in particular in buffalo, also suggesting that multiple FMDV serotypes might be involved with type O, SAT 2 and SAT 1 being dominant. Differences in serotype and spill-over risk between wildlife and livestock likely reflect regional geography, historical circulation and differing trade and livestock systems. PMID- 26156025 TI - Test characteristics and potential impact of the urine LAM lateral flow assay in HIV-infected outpatients under investigation for TB and able to self-expectorate sputum for diagnostic testing. AB - BACKGROUND: The commercially available urine LAM strip test, a point-of-care tuberculosis (TB) assay, requires evaluation in a primary care setting where it is most needed. There is currently inadequate data to guide implementation in TB and HIV-endemic settings. METHODS: Adult HIV-infected outpatients with suspected pulmonary TB able to self-expectorate sputum from four primary clinics in South Africa, Zambia and Tanzania underwent diagnostic evaluation [sputum smear microscopy, Xpert-MTB/RIF, and culture (reference standard)] as part of a prospective parent study. Urine LAM testing (grade-2 cut-point) was performed on archived samples. Performance characteristics of LAM alone or in combination with sputum-based diagnostics were evaluated. Potential impact on 2 and 6-month morbidity (TBscore), patient dropout rates, and prognosis (death/ loss to follow up) were evaluated. RESULTS: Among 583 participants with suspected TB that were HIV-infected or refused testing, the overall LAM sensitivity (95 % CI; n/N) and in the CD4 <= 100 cells/mm(3) sub-group was 22.7 % (16.6-28.7; 41/181) and 30.4 % (17.1-43.7; 14/46), respectively. Overall specificity was 93.0 % (90.5-95.6; 361/388). Amongst culture-positive TB cases, adjunctive LAM testing did not improve the sensitivity of either sputum Xpert-MTB/RIF [78.2 % (69.8-86.7; 72/92) versus 76.1 % (67.4-84.8; 70/92), p = 0.7] or smear-microscopy [56.2 % (45.9 66.5; 50/89) versus 43.8 % (33.5-54.1; 39/89), p = 0.1). Clinic-based LAM, as an adjunct to either smear microscopy or Xpert MTB/RIF same-day testing, would neither have decreased patient dropout, nor increased same-day treatment initiation in this clinical setting where same-day chest radiography was available. LAM positivity was associated with 6-month lost-to-follow-up/death (AOR 4.4; p = 0.002) but not TBscore (at baseline or change in TBscore 2-months post-treatment) (p = 0.17). CONCLUSIONS: In African HIV-TB co-infected outpatients able to self-expectorate sputum LAM had limited sensitivity even at low CD4 counts, and offered no significant incremental diagnostic yield over Xpert-MTB/RIF or smear microscopy. In primary care clinics with chest radiography and where empiric TB treatment is common, LAM seems unlikely to improve rates of same-day treatment initiation and patient dropout, however, the ability of LAM to identify patients at high risk of death or lost-to-follow-up may offer important prognostic value. PMID- 26156029 TI - Synthesis of self-reporting polymeric nanoparticles for in situ monitoring of endocytic microenvironmental pH. AB - The bis(pyrene) conjugated pH-sensitive polymers () were synthesized and self assembled into nanoparticles through hydrophobic interactions. The Nile red (NR) loaded nanoparticles showed red emission due to the FRET effect. The nanoparticles entered cells via endocytosis, and the microenvironmental pH in the endocytosis process was monitored in situ by the simultaneous dual-wavelength fluorescence changes. PMID- 26156030 TI - Excellent very early neointimal coverage of bioactive stents by optical coherence tomography. AB - OBJECTIVES: In a prospective study, we explored the extent of neointimal coverage of stent struts by optical coherence tomography 14 days following the implantation of bioactive stents in an unselected cohort. DESIGN: We enrolled 15 consecutive patients who underwent bioactive stent implantation. Optical coherence tomography images were obtained at 14-day follow-up. Morphometric analysis, strut coverage, strut apposition, neointimal hyperplasia, and possible thrombosis were evaluated at 1-mm intervals. Binary stent strut coverage was defined as the percentage of covered struts of all analyzed struts. RESULTS: Patients underwent optical coherence tomography examination at an average of 14.5 +/- 2.3 days following stent implantation. Mean age was 62 +/- 11 years; 86.7% were males; 26.7% diabetic. Three-hundred eighteen cross-sections were analyzed, including 2935 struts, an average of 9.2 +/- 3 struts per cross-section. Binary stent strut coverage was 96.3%; the prevalence of malapposed struts 1.8%. No thrombi were detected. Mean neointimal hyperplasia thickness was 71.5 +/- 53.7 MUm. CONCLUSIONS: In the current evaluation by optical coherence tomography at 14 day follow-up after bioactive stent implantation in an unselected cohort, binary stent strut coverage was fairly adequate, and the prevalence of malapposed struts was low. PMID- 26156031 TI - Intermittent insulin treatment mimics ischemic postconditioning via MitoKATP channels, ROS, and RISK. AB - OBJECTIVES: It has previously been demonstrated that 15-min continuous insulin infusion at immediate reperfusion affords cardioprotection. This study sought to reduce the treatment time of insulin and test if intermittent insulin infusions can mimic ischemic postconditioning. DESIGN: In a Langendorff perfused rat heart model of regional ischemia, hearts were at the onset of reperfusion subjected to either 5- or 1-min continuous insulin infusion or 3 * 30 s intermittent insulin infusions (InsPost); with or without inhibitors of Akt (SH-6), p70s6-kinase (rapamycin), mitochondrial ATP-sensitive potassium channels (5-hydroxydecanoic acid [5-HD]), or a scavenger of reactive oxygen species (ROS; 2-mercaptopropionyl glycine [MPG]). Infarct size is expressed as percent of area at risk and presented as mean +/- standard error of the mean or s.e.m. RESULTS: Only InsPost was able to reduce infarct size compared with controls (InsPost 33 +/- 6% vs. Ctr 52 +/- 4%, p < 0.05.). This cardioprotection was abrogated by co-administering SH 6, rapamycin, 5-HD, or MPG. (InsPost + SH-6 56 +/- 9%, InsPost + Rapa 55 +/- 8%, InsPost + 5-HD 56 +/- 7%, InsPost + MPG 60 +/- 3% vs. InsPost 33 +/- 6% p < 0.05). These results were corroborated by a significant increase in phosphorylated Akt and p70s6k in the InsPost group compared with controls. CONCLUSION: Short intermittent insulin infusions can mimic ischemic postconditioning and reduce myocardial infarct size via Akt/p70s6k and mKATP channels/ROS-dependent signaling. PMID- 26156032 TI - Epidemic Wave Dynamics Attributable to Urban Community Structure: A Theoretical Characterization of Disease Transmission in a Large Network. AB - BACKGROUND: Multiple waves of transmission during infectious disease epidemics represent a major public health challenge, but the ecological and behavioral drivers of epidemic resurgence are poorly understood. In theory, community structure-aggregation into highly intraconnected and loosely interconnected social groups-within human populations may lead to punctuated outbreaks as diseases progress from one community to the next. However, this explanation has been largely overlooked in favor of temporal shifts in environmental conditions and human behavior and because of the difficulties associated with estimating large-scale contact patterns. OBJECTIVE: The aim was to characterize naturally arising patterns of human contact that are capable of producing simulated epidemics with multiple wave structures. METHODS: We used an extensive dataset of proximal physical contacts between users of a public Wi-Fi Internet system to evaluate the epidemiological implications of an empirical urban contact network. We characterized the modularity (community structure) of the network and then estimated epidemic dynamics under a percolation-based model of infectious disease spread on the network. We classified simulated epidemics as multiwave using a novel metric and we identified network structures that were critical to the network's ability to produce multiwave epidemics. RESULTS: We identified robust community structure in a large, empirical urban contact network from which multiwave epidemics may emerge naturally. This pattern was fueled by a special kind of insularity in which locally popular individuals were not the ones forging contacts with more distant social groups. CONCLUSIONS: Our results suggest that ordinary contact patterns can produce multiwave epidemics at the scale of a single urban area without the temporal shifts that are usually assumed to be responsible. Understanding the role of community structure in epidemic dynamics allows officials to anticipate epidemic resurgence without having to forecast future changes in hosts, pathogens, or the environment. PMID- 26156033 TI - High-resolution OrbitrapTM-based mass spectrometry for rapid detection of peanuts in nuts. AB - Peanut represents one of the most harmful allergenic foods capable of triggering severe and sometimes lethal reactions in allergic consumers upon ingestion of even small amounts. Several proteins capable of inducing allergic reactions that have been recognised by patients' IgE antibodies have been identified from this nut source. Methods mainly based on ELISA assays have been developed in order to detect peanuts in several food commodities. In addition LC-MS/MS methods based on different mass analysers have also been devised for tracing peanut contamination in different foods achieving low limits of detection. The applicability of a benchtop high-resolution ExactiveTM mass spectrometer has never been investigated for the rapid screening of peanut contamination in complex food matrices like mixtures of nuts. We report in this paper the design of suitable peanut markers and the development of an high-resolution OrbitrapTM mass spectrometer-based method for peanut detection in a mixture of nuts species. With this aim, different types of samples were prepared: (1) nuts-based powder made up of a mixture of hazelnuts, pistachios, almonds and walnuts; and (2) nuts powder fortified with peanuts. Different levels of fortifications were produced and the applicability of the method was tested. Finally, a subset of six peptides fulfilling specific analytical requirements was chosen to check the suitability of the method tailored to the detection of peanuts in nuts-based products, and two of them, peptides VYD and WLG, were selected as quantitative markers. The method proved to be a suitable screening tool to assess the presence of traces of peanuts in other tree nuts with a limit of detection as low as 4 ug of peanuts proteins or 26 ug of peanuts in 1 g of matrix. PMID- 26156034 TI - Results of surgery plus postoperative radiotherapy for patients with malignant parotid tumor. AB - PURPOSE: The latest version of the World Health Organization (WHO) histologic classification of salivary gland malignancies was published in 2005. To contribute to data accumulation on the basis of this latest version, a retrospective study was performed. MATERIALS AND METHODS: Participants comprised 27 patients who underwent postoperative radiotherapy between 2000 and 2013. Two, eight, and 17 patients were allocated to low, intermediate, and high-grade groups, respectively, in accordance with the latest WHO classification. The radiation field included the tumor bed and ipsilateral regional lymph nodes for 25 patients. The radiation dose was 46-60 Gy (median 56 Gy). RESULTS: Median duration of follow-up was 41 months. Five-year locoregional control was 89 %. Two patients experienced local recurrence and 7 patients developed distant metastases. No patients in the low or intermediate-grade groups developed distant metastases. Overall 3 and 5-year survival for all patients were 81 and 75 %, respectively. Five-year overall survival for patients in the low and intermediate grade groups was 100 %, compared with 59 % for patients in the high-grade group (p = 0.03). CONCLUSION: Favorable locoregional control was achieved for patients with malignant parotid tumors who underwent surgery plus postoperative radiotherapy. Patients with high-grade tumors frequently experienced distant metastases and prognosis was poor. PMID- 26156035 TI - Nanostructured lipid carriers for percutaneous administration of alkaloids isolated from Aconitum sinomontanum. AB - BACKGROUND: Lipid-based nanosystems have great potential for transdermal drug delivery. In this study, nanostructured lipid carriers (NLCs) for short-acting alkaloids lappacontine (LA) and ranaconitine (RAN) isolated from Aconitum sinomontanum (AAS) at 69.47 and 9.16% (w/w) yields, respectively, were prepared to enhance percutaneous permeation. Optimized NLC formulations were evaluated using uniform design experiments. Microstructure and in vitro/in vivo transdermal delivery characteristics of AAS-loaded NLCs and solid lipid nanoparticles (SLNs) were compared. Cellular uptake of fluorescence-labeled nanoparticles was probed using laser scanning confocal microscopy and fluorescence-activated cell sorting. Nanoparticle integrity during transdermal delivery and effects on the skin surface were also investigated. RESULTS: NLC formulations were less cytotoxic than the AAS solution in HaCaT and CCC-ESF cells. Moreover, coumarin-6-labeled NLCs showed biocompatibility with HaCaT and CCC-ESF cells, and their cellular uptake was strongly affected by cholesterol and lipid rafts. Significantly greater cumulative amounts of NLC-associated LA and RAN than SLN-associated alkaloids penetrated the rat skin in vitro. In vivo microdialysis showed higher area under the concentration-time curve (AUC)0-t for AAS-NLC-associated LA and RAN than for AAS-SLN-associated alkaloids. CONCLUSIONS: NLC formulations could be good transdermal systems for increasing biocompatibility and decreasing cytotoxicity of AAS. AAS-NLCs showed higher percutaneous permeation than the other preparations. These findings suggest that NLCs could be promising transdermal delivery vehicles for AAS. PMID- 26156036 TI - The distribution, diversity, and importance of 16S rRNA gene introns in the order Thermoproteales. AB - BACKGROUND: Intron sequences are common in 16S rRNA genes of specific thermophilic lineages of Archaea, specifically the Thermoproteales (phylum Crenarchaeota). Environmental sequencing (16S rRNA gene and metagenome) from geothermal habitats in Yellowstone National Park (YNP) has expanded the available datasets for investigating 16S rRNA gene introns. The objectives of this study were to characterize and curate archaeal 16S rRNA gene introns from high temperature habitats, evaluate the conservation and distribution of archaeal 16S rRNA introns in geothermal systems, and determine which "universal" archaeal 16S rRNA gene primers are impacted by the presence of intron sequences. RESULTS: Several new introns were identified and their insertion loci were constrained to thirteen locations across the 16S rRNA gene. Many of these introns encode homing endonucleases, although some introns were short or partial sequences. Pyrobaculum, Thermoproteus, and Caldivirga 16S rRNA genes contained the most abundant and diverse intron sequences. Phylogenetic analysis of introns revealed that sequences within the same locus are distributed biogeographically. The most diverse set of introns were observed in a high-temperature, circumneutral (pH 6) sulfur sediment environment, which also contained the greatest diversity of different Thermoproteales phylotypes. CONCLUSIONS: The widespread presence of introns in the Thermoproteales indicates a high probability of misalignments using different "universal" 16S rRNA primers employed in environmental microbial community analysis. PMID- 26156037 TI - Early postoperative magnet resonance tomography after resection of cerebral metastases. AB - BACKGROUND: In contrast to malignant gliomas, the impact of an early postoperative MRI after surgery of cerebral metastasis is still unclear. The present study analyses early MRI-based postoperative resection controls and incidence of in-brain progression in 116 patients suffering from 130 cerebral metastases. METHODS: The extent of surgical resection was verified by an early postoperative contrast-enhanced 1.5-T MRI within 72 h after surgery of cerebral metastases and correlated with in-brain progression, leptomeningeal carcinomatosis, and progression-free survival. RESULTS: MRI confirmed complete resection was seen in 80 out of 130 metastases (61.5 %). In 24 metastases (18.5 %), no final decision on degree of resection could be made. Residual tumor was seen in 26 cases (20 %). Local in-brain progression was observed in 40 of 130 (30.8 %) cases. The incidence of in-brain progression significantly correlated with dural contact of the metastasis (p < 0.05) and residual tumor on early postoperative MRI (p < 0.0001). The odds ratio for local recurrence with residual tumor is 8.2-fold compared to no residual tumor. CONCLUSIONS: Residual tumor after metastasis extirpation was shown in nearly 20 % of patients by an early postoperative MRI and significantly correlated with local in-brain progression. Furthermore, dural contact of cerebral metastases was identified as a risk factor for local recurrence. Further studies are mandatory to clearly identify the incidence of incomplete resections of cerebral metastases and their oncologic impact. An early postoperative MRI after resection of cerebral metastases is recommended as residual tumor promotes local recurrence. PMID- 26156038 TI - Editorial: Health Impact and Management of a Disrupted Circadian Rhythm and Sleep in Critical Illnesses. PMID- 26156039 TI - [Surgical treatment of scoliosis in childhood and adolescence: Age group and etiology-related indications and choice of instrumentation]. AB - The indications for a corrective surgical procedure for the complex 3-dimensional deformations of the spine collectively known under the term scoliosis, essentially depend on knowledge of the underlying etiology, the time of initial diagnosis in relation to the growth curve of the child and on considerations about the general operability of the patient. An early onset of scoliosis in childhood under defined diagnostic criteria is usually associated with a fast progression of spinal curvature and requires early surgical intervention during the growth period, while scoliosis in adolescence often allows a delayed surgical intervention until all conservative means have been taken into consideration. Corrective measures in the growing spine require procedures and adjustable hardware which can be adapted to vertebral and thoracic growth and thus anticipate the threat of pulmonary insufficiency due to postural and spinal collapse. Towards the end of puberty when spinal growth slowly comes to an end, corrective spinal fusion procedures are considered in those cases of early and late onset scoliosis, where curvature progression is likely to occur. PMID- 26156040 TI - Potential New Agents for the Management of Hyperkalemia. AB - Hyperkalemia is a common electrolyte disturbance with multiple potential etiologies. It is usually observed in the setting of reduced renal function. Mild to moderate hyperkalemia is usually asymptomatic, but is associated with poor prognosis. When severe, hyperkalemia may cause serious acute cardiac arrhythmias and conduction abnormalities, and may result in sudden death. The rising prevalence of conditions associated with hyperkalemia (heart failure, chronic kidney disease, and diabetes) and broad use of renin-angiotensin-aldosterone system (RAAS) inhibitors and mineralocorticoid receptor antagonists (MRAs), which improve patient outcomes but increase the risk of hyperkalemia, have led to a significant rise in hyperkalemia-related hospitalizations and deaths. Current non invasive therapies for hyperkalemia either do not remove excess potassium or have poor efficacy and tolerability. There is a clear need for safer, more effective potassium-lowering therapies suitable for both acute and chronic settings. Patiromer sorbitex calcium and sodium zirconium cyclosilicate (ZS-9) are two new potassium-lowering compounds currently in development. Although they have not yet been approved by the US FDA, both have demonstrated efficacy and safety in recent trials. Patiromer sorbitex calcium is a polymer resin and sorbitol complex that binds potassium in exchange for calcium; ZS-9, a non-absorbed, highly selective inorganic cation exchanger, traps potassium in exchange for sodium and hydrogen. This review discusses the merits of both novel drugs and how they may help optimize the future management of patients with hyperkalemia. PMID- 26156041 TI - Involvement of epithelial Wntless in the regulation of postnatal hair follicle morphogenesis. AB - The roles of the Wnt cargo receptor Wntless (Wls) during hair follicle (HF) induction and postnatal HF cycling in skin have been elucidated. However, whether Wls regulates postnatal HF morphogenesis remains unclear. In this study, we found that Wls is expressed in developing HF during the morphogenesis stage after birth. By knocking out Wls in mouse skin epithelia with hypomorphic K14-cre, we found that Wls is required for normal HF morphogenesis. Wls-deficient HFs prematurely regressed, which was possibly caused by abnormally activated TGF beta/JNK pathway. Although Wls was reported to be a direct target of the Wnt/beta catenin pathway, we found that epithelial beta-catenin was not necessary to maintain Wls expression. Therefore, other signals are involved in regulating Wls transcription in mouse skin. PMID- 26156042 TI - Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan. AB - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a severe life threatening disease with frequent progression to end-stage renal disease (ESRD). Eculizumab, a humanized anti-C5 monoclonal antibody targeting the activated complement pathway, has recently been introduced as a novel therapy against aHUS. We, therefore, investigated the efficacy and safety of eculizumab in Japanese pediatric patients. METHODS: We retrospectively analyzed clinical course and laboratory data of the first ten children with aHUS treated with eculizumab nationwide. RESULTS: Seven patients were resistant to plasma therapy and three were dependent on it. Causative gene mutations were found in five patients. Two patients had anti-complement factor H autoantibody. Three patients had a family history of thrombotic microangiopathy (TMA). After initiation of eculizumab, all patients immediately achieved hematological remission and could successfully discontinue plasma therapy. The median periods to normalization of platelet count, lactate dehydrogenase levels and disappearance of schistocytes were 5.5, 17 and 12 days, respectively. Nine patients recovered their renal function and the median period to terminate renal replacement therapy (RRT) was 3 days. However, two patients progressed to ESRD and required chronic RRT at the last observation. No patients had a relapse of TMA under regular eculizumab therapy. No serious adverse events occurred during the follow-up period. CONCLUSIONS: Eculizumab is efficacious and well-tolerated therapy for children with aHUS. Although pathogenic mutations could not be detected in five patients, all patients showed immediate normalization of hematological abnormalities, strongly suggesting complement-related aHUS. This prompt hematological amelioration can become an indicator for therapeutic efficacy of eculizumab. However, appropriate indications and optimal duration of the treatment remain unclear. PMID- 26156043 TI - MMP-3 can distinguish isolated PMR from PMR with GCA: A retrospective study regarding PMR and GCA in Japan. AB - OBJECTIVE: We sought to identify clinical features at diagnosis that can distinguish isolated polymyalgia rheumatica (PMR) without giant cell arteritis (GCA) from PMR with GCA, and clinical features at diagnosis of isolated PMR that can predict subsequent relapse and corticosteroid discontinuation. METHODS: A retrospective study of 115 patients with isolated PMR and 29 patients with GCA was performed. A comparison between isolated PMR patients, GCA patients (with or without PMR), and PMR with GCA patients was performed. Predictors of relapse and corticosteroid discontinuation were identified using a logistic regression in the patients with isolated PMR. RESULTS: Matrix metalloproteinase-3 (MMP-3) level was significantly different among the patient groups. MMP-3: 230.5 +/- 201.5 ng/mL in isolated PMR, 80.5 +/- 47.5 ng/mL in GCA (p < 0.01), and 96.8 +/- 54.8 ng/mL in PMR with GCA (p = 0.03). In the patients with isolated PMR, female gender (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.16-6.41; p < 0.05) and creatinine (Cr) < 50 MUmol/L (OR, 2.48; 95% CI, 1.02-5.99; p < 0.05) were significant prognostic factors that predicted relapse. CONCLUSION: A low level of MMP-3 is an excellent positive predictor for PMR with GCA. Among patients with isolated PMR, female gender and Cr < 50 MUmol/L were significant prognostic factors that predicted relapse. PMID- 26156044 TI - Longer operative time is the risk for delayed wound healing after forefoot surgery in patients with rheumatoid arthritis. AB - OBJECTIVES: Forefoot deformities are common in patients with rheumatoid arthritis (RA) and often require operative treatment. There is a high rate of delayed wound healing after foot surgery, especially among patients with RA. The aim of this study was to identify risk factors of delayed wound healing in RA patients who had undergone forefoot surgery. METHODS: This study was a retrospective observational study designed to analyze the outcomes of all consecutive RA patients who had undergone toe arthroplasty from April 2010 through May 2014 at a single institute. Putative risk factors for delayed wound healing were assessed using univariate logistic regression analysis. Variables with alpha = 0.1 were then subjected to stepwise multivariate logistic regression analysis. RESULTS: A total of 192 RA patients (192 feet) were included in this study. Delayed wound healing was seen in 40 feet (40/192 [20.8%]). A stepwise multivariate logistic regression analysis revealed that longer operative time was the risk factor associated with delayed wound healing in RA patients undergoing forefoot surgery (p = 0.028, odds ratio = 1.19 [per 10 min], 95% confidence interval [CI]: 1.07 1.32). CONCLUSIONS: This finding emphasizes the importance of preventing operative complications during forefoot surgery. PMID- 26156045 TI - Measuring Effortful Control Using the Children's Behavior Questionnaire-Very Short Form: Modeling Matters. AB - Effortful control (EC) is an important concept in the research on self-regulation in children. We tested 2 alternative factor models of EC as measured by the Children's Behavior Questionnaire-Very Short Form (CBQ-VSF; Putnam & Rothbart, 2006 ) in a large sample of preschoolers (N = 1,007): 1 lower order and 1 hierarchical second-order structure. Additionally, convergent and predictive validity of EC as measured by the CBQ-VSF were investigated. The results supported a hierarchical model. Moderate convergent validity of the second-order latent EC factor was found in that it correlated with compliance and observed EC tasks. Both CBQ-VSF EC measures were also negatively correlated with child physical aggression. The results have implications for the measurement, modeling, and interpretation of EC applying the CBQ. PMID- 26156046 TI - Ethnic diversity in the genetics of venous thromboembolism. AB - Genetic susceptibility is considered as a crucial factor for the development of venous thromboembolism (VTE). Epidemiologic and genetic studies have revealed clear disparities in the incidence of VTE and the distribution of genetic factors for VTE in populations stratified by ethnicity worldwide. While gain-of-function polymorphisms in the procoagulant genes are common inherited factors in European origin populations, the most prevalent molecular basis for venous thrombosis in Asians is confirmed to be dysfunctional variants in the anticoagulant genes. With the breakthrough of genomic technologies, a set of novel common alleles and rare mutations associated with VTE have also been identified, in different ethnic groups. Several putative pathways contributing to the pathogenesis of thrombophilia in populations of African-ancestry are largely unknown, as current knowledge of hereditary and acquired risk factors do not fully explain the highest risk of VTE in Black groups. In-depth studies across diverse ethnic populations are needed to unravel the whole genetics of VTE, which will help developing individual risk prediction models and strategies to minimise VTE in all populations. PMID- 26156047 TI - Fish consumption and risk of myeloma: a meta-analysis of epidemiological studies. AB - PURPOSE: The relationship between fish consumption and multiple myeloma (MM) risk has not been consistent across epidemiological studies. We quantitatively assessed the aforementioned association through a systematic review and meta analysis. METHODS: PubMed was searched through the end of March 2015 for eligible studies. Fixed or random effects models were used to pool risk estimates. Five case-control studies that involved 1,366 cases and 8,259 controls were identified. Three studies had high methodological quality, and two studies had low quality based on the Newcastle-Ottawa Quality Assessment Scale. RESULTS: After pooling all risk estimates, a significant inverse association was found between the highest category versus lowest category of fish consumption and MM risk (relative risk = 0.65, 95% confidence interval = 0.46-0.91), with relatively high heterogeneity (I(2) = 55.6%). No evidence of publication bias was detected. The inverse association persisted in all subgroups according to study quality, type, location, and whether there were adjustments for confounders, although statistical significance was not detected in all strata. The dose-response analysis suggested a nonlinear dose-response relationship for the association, with the lowest risk linked to fish consumption once per week. CONCLUSION: This meta-analysis suggests that the highest versus lowest category of fish consumption is inversely associated with MM risk. Furthermore, a nonlinear dose response relationship was suggested for the association. Because this evidence is based on a small number of retrospective studies with mixed quality and because high heterogeneity was detected, further prospective studies are warranted to validate our findings and better characterize the relationship. PMID- 26156048 TI - Job Satisfaction Among Gerontological Social Workers in Ontario, Canada. AB - Little is known about job satisfaction among Canada's social work workforce in aging, although social workers remain a key component of interdisciplinary care in health and social service settings. This study begins to address this gap in knowledge by examining individual, interpersonal, and job-design factors influencing the job satisfaction of gerontological social workers in Ontario. Data were collected via two online surveys with a sample drawn from the Ontario Association of Social Workers' membership list (N = 104). A multiple regression model explained 37% of the variance in job satisfaction, F = 5.47[10, 93], p < .001). Three independent variables were significant (positive affect, beta = .21; promotional chances, beta = .21; and client acuity, beta = -.18). The results suggest the importance of promoting strategies for enhancing job satisfaction, advancing promotional opportunities for social work clinicians, and providing educational and clinical supports to clinicians. PMID- 26156049 TI - Statistical removal of background signals from high-throughput (1)H NMR line broadening ligand-affinity screens. AB - NMR ligand-affinity screens are vital to drug discovery, are routinely used to screen fragment-based libraries, and used to verify chemical leads from high throughput assays and virtual screens. NMR ligand-affinity screens are also a highly informative first step towards identifying functional epitopes of unknown proteins, as well as elucidating the biochemical functions of protein-ligand interaction at their binding interfaces. While simple one-dimensional (1)H NMR experiments are capable of indicating binding through a change in ligand line shape, they are plagued by broad, ill-defined background signals from protein (1)H resonances. We present an uncomplicated method for subtraction of protein background in high-throughput ligand-based affinity screens, and show that its performance is maximized when phase-scatter correction is applied prior to subtraction. PMID- 26156050 TI - delta2H, delta13C and delta18O from whole wood, alpha-cellulose and lignin methoxyl groups in Pinus sylvestris: a multi-parameter approach. AB - Novel tree ring parameters - delta(13)C and delta(2)H from methoxyl groups - have been developed to reconstruct palaeoclimate. Tests with delta(13)C and delta(18)O derived from whole wood and cellulose samples, however, indicated differences in the isotopic composition and climate signal, depending on the extracted wood component. We assess this signal dependency by analysing (i) delta(13)C and delta(18)O from whole wood and cellulose and (ii) delta(13)C and delta(2)H from methoxyl groups, using Pinus sylvestris L. growing near Altenkirchen (Germany). Results indicate significant correlations among the time series derived from whole wood, cellulose, and lignin methoxyl groups. Compared with the whole wood samples, delta(13)C from methoxyl groups showed a different and overall lower response to climate parameters. On the other hand, delta(2)H from methoxyl groups showed high correlations with temperature and was also correlated with ring width, indicating its potential as a temperature proxy. Isotope time series with the highest correlation with climatic parameter were: (i) whole wood and cellulose delta(13)C with growing season precipitation and summer temperature; (ii) methoxyl groups with spring precipitation; (iii) whole wood and cellulose delta(18)O correlates with annual evapotranspiration and water balance; and (iv) methoxyl group delta(2)H with spring temperatures. These findings reveal that multiple climate elements can be reconstructed from different wood components and that whole wood proxies perform comparably to cellulose time series. PMID- 26156051 TI - Hepatotoxicity due to chenodeoxycholic acid supplementation in an infant with cerebrotendinous xanthomatosis: implications for treatment. AB - We present a two-week old girl who was diagnosed with cerebrotendinous xanthomatosis (CTX), an inborn error of bile acid synthesis, after a diagnostic workup for convulsions which were shown to be caused by a parechovirus encephalitis. The diagnosis of CTX was confirmed with CYP27A1 mutation analysis. She was started on chenodeoxycholic acid (CDCA) supplementation, which inhibits cholestanol production through a feedback mechanism, at the advised dosage of 15 mg/kg/day. Within 6 weeks, she developed jaundice with hepatomegaly. CDCA supplementation was stopped after which liver size and function rapidly normalised. CDCA supplementation was then restarted and maintained at 5 mg/kg/day. Cholestanol, liver enzymes and total bilirubin were frequently monitored in the patient, who is now 2.8 years of age, and have remained within normal range. Her psychomotor development has been normal. CONCLUSION: adequate metabolic control was achieved in an infant with CTX with CDCA supplementation at a dosage of 5 mg/kg/day and was well tolerated. CDCA supplementation at 15 mg/kg/day seems hepatotoxic in infants and should not be used. This is relevant in view of the possible inclusion of CTX in newborn screening programs in the near future. WHAT IS KNOWN: Cerebrotendinous xanthomatosis (CTX), an inborn error of bile acid synthesis, is a progressive neurological disorder. Symptoms of CTX can be halted, and likely prevented, with chenodeoxycholic acid (CDCA) supplementation, making CTX a good candidate for newborn screening. What is New: CDCA supplementation at the advised dosage of 15 mg/kg/day in children seems hepatoxic in infants with CTX. Adequate metabolic control in an infant with CTX was achieved with CDCA supplementation at 5 mg/kg/day and well tolerated. PMID- 26156052 TI - Epidemiology of multiple sclerosis in the pediatric population of Sardinia, Italy. AB - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Several authors report MS affecting not only young adults but also children and adolescents. Sardinia is one of the regions at the highest risk for MS worldwide in the adult population; to date, no definite data exist on the pediatric population. The aim of this study was to estimate the incidence and prevalence of pediatric MS (pMS) in northern Sardinia. Patients with diagnosis of optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), demyelinating disorders, MS, or clinically isolated syndrome (CIS) according to McDonald criteria were enrolled, when disease onset occurred within the range of 0-18 years. From January 1, 2001 to December 31, 2012, 21 cases of pMS and 5 cases of CIS were found in northern Sardinia. The annual mean pMS incidence was 2.85 cases per 100,000 pediatric population, and the annual mean CIS incidence was 0.68 cases per 100,000 pediatric population. The pMS and CIS prevalence computed on 31 December 2012 was 26.92 and 6.41 per 100,000 pediatric population, respectively. CONCLUSION: Our pMS data among Sardinians corroborate the epidemiological scenario described in the adult population being the incidence estimates significantly higher than those reported elsewhere. WHAT IS KNOWN: Sardinia is one of the regions at the highest risk for MS worldwide in the adult population. To date, no definite data exist on the pediatric population. WHAT IS NEW: The pediatric MS incidence in Sardinia is estimated to be significantly higher than those reported elsewhere. The pediatric MS prevalence in Sardinia is among the highest values worldwide. PMID- 26156053 TI - One-Time Addition of Nano-TiO2 Triggers Short-Term Responses in Benthic Bacterial Communities in Artificial Streams. AB - Nano-TiO2 is an engineered nanomaterial whose production and use are increasing rapidly. Hence, aquatic habitats are at risk for nano-TiO2 contamination due to potential inputs from urban and suburban runoff and domestic wastewater. Nano TiO2 has been shown to be toxic to a wide range of aquatic organisms, but little is known about the effects of nano-TiO2 on benthic microbial communities. This study used artificial stream mesocosms to assess the effects of a single addition of nano-TiO2 (P25 at a final concentration of 1 mg l(-1)) on the abundance, activity, and community composition of sediment-associated bacterial communities. The addition of nano-TiO2 resulted in a rapid (within 1 day) decrease in bacterial abundance in artificial stream sediments, but bacterial abundance returned to control levels within 3 weeks. Pyrosequencing of partial 16S rRNA genes did not indicate any significant changes in the relative abundance of any bacterial taxa with nano-TiO2 treatment, indicating that nano-TiO2 was toxic to a broad range of bacterial taxa and that recovery of the bacterial communities was not driven by changes in community composition. Addition of nano-TiO2 also resulted in short-term increases in respiration rates and denitrification enzyme activity, with both returning to control levels within 3 weeks. The results of this study demonstrate that single-pulse additions of nano-TiO2 to aquatic habitats have the potential to significantly affect the abundance and activity of benthic microbial communities and suggest that interactions of TiO2 nanoparticles with environmental matrices may limit the duration of their toxicity. PMID- 26156054 TI - Genome-wide identification and Phylogenic analysis of kelch motif containing ACBP in Brassica napus. AB - BACKGROUND: Acyl-coA binding proteins (ACBPs) bind long chain acyl-CoA esters with very high affinity. Their possible involvement in fatty acid transportation from the plastid to the endoplasmic reticulum, prior to the formation of triacylglycerol has been suggested. Four classes of ACBPs were identified in Arabidopsis thaliana: the small ACBPs, the large ACBPs, the ankyrin repeats containing ACBPs and the kelch motif containing ACBPs. They differed in structure and in size, and showed multiple important functions. In the present study, Brassica napus ACBPs were identified and characterized. RESULTS: Eight copies of kelch motif ACBPs were cloned, it showed that B. napus ACBPs shared high amino acid sequence identity with A. thaliana, Brassica rapa and Brassica oleracea. Furthermore, phylogeny based on domain structure and comparison map showed the relationship and the evolution of ACBPs within Brassicaceae family: ACBPs evolved into four separate classes with different structure. Chromosome locations comparison showed conserved syntenic blocks. CONCLUSIONS: ACBPs were highly conserved in Brassicaceae. They evolved from a common ancestor, but domain duplication and rearrangement might separate them into four distinct classes, with different structure and functions. Otherwise, B. napus inherited kelch motif ACBPs from ancestor conserving chromosomal location, emphasizing preserved synteny block region. This study provided a first insight for exploring ACBPs in B. napus, which supplies a valuable tool for crop improvement in agriculture. PMID- 26156056 TI - Does Safety Have to Mean Control? PMID- 26156055 TI - Targeted BRAF and CTNNB1 next-generation sequencing allows proper classification of nonadenomatous lesions of the sellar region in samples with limiting amounts of lesional cells. AB - PURPOSE: To assess the role of high sensitivity next-generation sequencing (NGS) of CTNNB1 for the diagnosis of adamantinomatous craniopharyngiomas (aCPs) and of BRAF for that of papillary CPs (pCPs) in routinely processed surgical samples of non-adenomatous sellar lesions. METHODS: Forty-five cases of patients operated for non-adenomatous masses of the sellar region between 2004 and 2014 were retrieved from the files of the Anatomic Pathology unit of the Bellaria Hospital in Bologna, Italy. BRAF and CTNNB1 mutation status was analyzed by NGS in samples smaller than 1 cm(3) and histological re-evaluation was performed on all cases. RESULTS: CTNNB1 mutation analysis showed a sensitivity of 86.7 % and a specificity of 96.2 % for the diagnosis of aCPs. The specificity increased to 100 % considering that in one case, initially classified as a non-CP lesion (xanthogranuloma), the identification of a CTNNB1 S47R lead to histological re evaluation and reclassification of the lesion as aCP. BRAF mutation analysis had a sensitivity of 76.9 % and a specificity of 96.4 % for the diagnosis of pCPs. The specificity increased to 100 % considering that in one case, initially classified as a Rathke cyst, the identification of BRAF V600E lead to histological re-evaluation and reclassification of the lesion as pCP. CONCLUSIONS: This study confirms the diagnostic relevance of the molecular alterations recently identified in aCPs and pCPs and shows how the identification of BRAF and CTNNB1 mutations can be instrumental for the proper classification of samples that contain limiting amounts of diagnostic lesional tissue. PMID- 26156057 TI - Engagement as an Element of Safe Inpatient Psychiatric Environments. AB - BACKGROUND: The American Psychiatric Nurses Association (APNA) Institute for Safe Environments (ISE) has focused on key elements that affect safety in psychiatric treatment environments; one of these key elements is patient engagement. An ISE workgroup discussed and reviewed the literature on engagement and safety in inpatient psychiatric settings. This article presents what we have learned about the role that engagement plays in inpatient treatment of severely mentally ill individuals and evidence that links nurse-patient engagement to safety. OBJECTIVES: To describe, using supporting literature, the role that nurse-patient engagement plays in creating safe, therapeutic environments for individuals with severe mental illness. DESIGN: (1) Define engagement and describe why it is an important element of safe treatment environments; (2) identify what helps and what hinders patients in their engagement with nurses, and nurses in their engagement with patients; (3) describe how engagement may improve unit safety; and (4) propose recommendations and set future directions for practice, research, and education. CONCLUSION: Engagement may provide the foundation for safe, therapeutic, and recovery-oriented treatment. In the future, APNA's ISE plans to build upon this foundation by developing a clinical model of nurse-patient engagement and safety by drawing together emerging research and practice models. PMID- 26156058 TI - Commentary on "Engagement as an Element of Safe Inpatient Psychiatric Environments": Engagement Is Psychiatric-Mental Health Nursing. PMID- 26156059 TI - Exploration of Individual and Family Factors Related to Community Reintegration in Veterans With Traumatic Brain Injury. AB - BACKGROUND: Community reintegration (CR) poses a major problem for military veterans who have experienced a traumatic brain injury (TBI). Factors contributing to CR after TBI are poorly understood. OBJECTIVE: To address the gap in knowledge, an ecological framework was used to explore individual and family factors related to CR. DESIGN: Baseline data from an intervention study with 83 veterans with primarily mild to moderate TBI were analyzed. Instruments measured CR, depressive symptoms, physical health, quality of the relationship with the family member, and sociodemographics. Posttraumatic stress disorder and TBI characteristics were determined through record review. RESULTS: Five variables that exhibited significant bivariate relationships with CR (veteran rating of quality of relationship, physical functioning, bodily pain, posttraumatic stress disorder diagnosis, and depressive symptoms) were entered into hierarchical regression analysis. In the final analysis, the five variables together accounted for 35% of the variance, but only depression was a significant predictor of CR, with more depressed veterans exhibiting lower CR. CONCLUSIONS: Efforts to support CR of Veterans with TBI should carefully assess and target depression, a modifiable factor. PMID- 26156060 TI - Using Benford's law to investigate Natural Hazard dataset homogeneity. AB - Working with a large temporal dataset spanning several decades often represents a challenging task, especially when the record is heterogeneous and incomplete. The use of statistical laws could potentially overcome these problems. Here we apply Benford's Law (also called the "First-Digit Law") to the traveled distances of tropical cyclones since 1842. The record of tropical cyclones has been extensively impacted by improvements in detection capabilities over the past decades. We have found that, while the first-digit distribution for the entire record follows Benford's Law prediction, specific changes such as satellite detection have had serious impacts on the dataset. The least-square misfit measure is used as a proxy to observe temporal variations, allowing us to assess data quality and homogeneity over the entire record, and at the same time over specific periods. Such information is crucial when running climatic models and Benford's Law could potentially be used to overcome and correct for data heterogeneity and/or to select the most appropriate part of the record for detailed studies. PMID- 26156061 TI - Racial/ethnic differences in weekend delivery after induction of labor. AB - OBJECTIVE: To determine whether the frequency induction of labor (IOL) varies by day of the week based on maternal race/ethnicity. STUDY DESIGN: Gravid women in the US from 2007 to 2010 were stratified into <34, 34 to 36, 37 to 38 and ?39 weeks. Multivariable analyses estimated the association between weekend delivery, race/ethnicity (categorized as non-Hispanic white, Hispanic white, black and 'other') and their interaction with induction. RESULT: After 34 weeks, induction was less likely on the weekend (P<0.01) and less likely in black, Hispanic or 'other' women relative to non-Hispanic whites (P<0.01). However, there was a significant positive interaction between race/ethnicity and weekend delivery (P<0.001). During the late preterm gestation, weekend IOL was greater in black women (odds ratio, 1.08). CONCLUSION: The difference in IOL by race/ethnicity increased with gestational age. This difference was least on the weekends. PMID- 26156062 TI - Is routine preoperative transthoracic echocardiography necessary in newborns with myelomeningocele? AB - OBJECTIVE: Congenital heart disease (CHD) is common in newborns with myelomeningocele. Echocardiography before neonatal back closure has been recommended. Its utility in the era of prenatal diagnosis is unclear. STUDY DESIGN: We reviewed all newborns with myelomeningocele evaluated by preoperative echocardiography at our institution over 11 years. RESULT: Seventy-six successive newborns were identified. Ninety-one percent were prenatally diagnosed with myelomeningocele. In all, 1% had critical, 12% critical or non-critical and 22% critical, non-critical or possible CHD. The single case of critical CHD was both prenatally diagnosed and clinically identifiable. CONCLUSION: The prevalence of CHD in newborns with myelomeningocele is increased compared with the general population; however, critical disease is uncommon. We propose preoperative echocardiography is unnecessary when the myelomeningocele is prenatally diagnosed, antenatal cardiac screening is complete and normal, and the newborn is clinically well. PMID- 26156063 TI - Implementation of safe sleep practices in the neonatal intensive care unit. AB - OBJECTIVE: To increase the percentage of eligible infants engaging in safe sleep practices (SSP) in two level III neonatal intensive care units (NICUs) in the Boston, Massachusetts area. STUDY DESIGN: On the basis of eligibility criteria (?34 weeks or ?1800 g without acute medical conditions), all infants were eligible for two sleep practices: SSP or NICU therapeutic positioning (NTP) depending on their gestational age, weight, clinical illness and need for therapeutic interventions. Compliance with SSP was defined as: (1) supine positioning, (2) in a flat crib with no incline, (3) without positioning devices and (4) without toys, comforters or fluffy blankets. NTP comprised usual NICU care. Nursing education was comprised of a web-based learning module and in person teaching sessions with a study team member. Double-sided crib cards (SSP one side and NTP on the other) were attached to the bedside of every infant. Pre- and postintervention audits of all infants were carried out at both study sites. We compared compliance across all time points using generalized estimating equations to account for correlated data (SAS v9.3, Cary, NC, USA). RESULT: Of 755 cases, 395 (52.3%) were assessed to be eligible for SSP. From the pre- to post-intervention period, there was a significant improvement in overall compliance with SSP (25.9 to 79.7%; P-value<0.001). Adherence to each component of SSP also improved significantly following the intervention. CONCLUSION: Safe infant sleep practices can be integrated into the routine care of preterm infants in the NICU. Modeling SSP to families far in advance of hospital discharge may improve adherence to SSP at home and reduce the risk of sleep-related morbidity and mortality in this vulnerable population of infants. PMID- 26156064 TI - Dynamic thiol-disulfide homeostasis in hyperemesis gravidarum. AB - OBJECTIVE: To determine serum thiol-disulfide homeostasis in hyperemesis gravidarum. STUDY DESIGN: Twenty-six pregnant women with hyperemesis gravidarum and 37 healthy pregnant women were included in the study. Native thiol, disulfide and total thiol concentrations were measured with a novel automated method. RESULTS: Serum disulfide levels were 15.68+/-4.41 MUmol l(-1) in the hyperemesis gravidarum group and 13.49+/-2.81 MUmol l(-1) in the healthy group (P=0.031). Native thiol levels were 213.86+/-26.29 MUmol l(-1) in the hyperemesis gravidarum group and 232.18+/-19.21 MUmol l(-1) in healthy group (P=0.004), and total thiol levels were 245.23+/-28.58 MUmol l(-1) in the hyperemesis gravidarum group and 259.17+/-19.94 MUmol l(-1) in the healthy group (P=0.038). CONCLUSION: Native and total thiol were deficient in the hyperemesis gravidarum group and this deficiency was correlated with the severity of the disease. The thiol-disulfide balance has shifted to the oxidative side. This metabolic disturbance may have a role in the pathogenesis of hyperemesis gravidarum. PMID- 26156067 TI - Production of graphene oxide from pitch-based carbon fiber. AB - Pitch-based graphene oxide (p-GO) whose compositional/structural features are comparable to those of graphene oxide (GO) was firstly produced by chemical exfoliation of pitch-based carbon fiber rather than natural graphite. Incorporation of p-GO as nanofillers into poly(methyl methacrylate) (PMMA) as a matrix polymer resulted in excellent mechanical reinforcement. p-GO/PMMA nanocomposite (1 wt.-% p-GO) demonstrated 800% higher modulus of toughness of neat PMMA. PMID- 26156066 TI - Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus. AB - In order to elucidate the chemical structure of black to brown pigments, neuromelanins (NMs), in the substantia nigra (SN) and the locus coeruleus (LC) in the central nervous system of humans and other mammalian species during aging, chemical degradative methods are powerful tools. HPLC analysis after hydroiodic acid hydrolysis detected aminohydroxyphenylethylamines, aminohydroxyphenylacetic acids, and aminohydroxyethylbenzenes, which confirmed that SN-NM and LC-NM contain melanin derived not only from dopamine and norepinephrine (NE) but also from several other catecholic metabolites, such as 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxymandelic acid, 3,4 dihydroxyphenylethanol, and 3,4-dihydroxyphenylethylene glycol, in addition to the corresponding Cys-derivatives in varying degrees. However, hydroiodic acid hydrolysis showed that LC-NM produced the same degradation products as were detected in SN-NM. Thus, we needed to develop a new chemical detection method to validate the existence of NE in LC-NM. In the present study, we report that HCl hydrolysis of LC-NM in the presence of thioglycolic acid yields new products arising from substitution of the hydroxyl group by thioglycolic acid at the benzyl position of NE and cysteinyl-NE. This is the first chemical evidence showing that NE and cysteinyl-NE are incorporated into LC-NM. Using the chemical degradation methods for the determination of catechols in neuromelanin (NM), we have shown that dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4 dihydroxyphenylethanol (DOPE), and 3,4-dihydroxyphenylalanine (DOPA) are mainly responsible for the structure of NM from substantia nigra (SN), while norepinephrine (NE), 3,4-dihydroxymandelic acid (DOMA), and 3,4 dihydroxyphenylethylene glycol (DOPEG) are additionally responsible for the structure of NM from locus coeruleus (LC). PMID- 26156065 TI - A high burden of late-onset sepsis among newborns admitted to the largest neonatal unit in central Vietnam. AB - OBJECTIVE: The objective of this study is to determine the prevalence, causes and outcome of sepsis in hospitalized neonates in the largest neonatal unit in central Vietnam. STUDY DESIGN: A 1-year prospective cohort study of newborns admitted to the neonatal unit in Da Nang. A sepsis work-up including blood culture was undertaken before commencing antibiotics for neonates with suspected sepsis. RESULT: Of 2555 neonatal admissions, 616 neonates had 729 episodes of suspected invasive sepsis. A pathogen was isolated from blood in 115 (16%) episodes in 106 neonates. The prevalence of early-onset sepsis (EOS) was 8 (95% confidence interval (CI): 4 to 11) per 1000 admissions, and of late-onset sepsis (LOS) was 34 (95% CI: 27 to 41) per 1000 admissions. Of 86 neonates with LOS, 69 (80%) also fulfilled the criteria for nosocomial sepsis. The commonest bacterial causes of EOS were coagulase-negative Staphylococcus (CoNS) and Staphylococcus aureus, and of LOS were Acinetobacter, CoNS and Klebsiella pneumoniae. Fungal sepsis occurred in 35 neonates of which most were nosocomial sepsis. In vitro resistance to multiple antibiotics was common among Gram-negative bacteria. Antibiotics were prescribed and given to 68% of all admissions, and 14% of all admissions received four or more different antibiotics. The case fatality rate for confirmed sepsis was 46%. CONCLUSION: Late-onset, nosocomial sepsis was common and associated with a high mortality in hospitalized newborns in the largest neonatal unit in central Vietnam. These findings highlighted the need for improved infection control measures and antibiotic stewardship, which have since been implemented. PMID- 26156068 TI - Growth kinetics of white graphene (h-BN) on a planarised Ni foil surface. AB - The morphology of the surface and the grain orientation of metal catalysts have been considered to be two important factors for the growth of white graphene (h BN) by chemical vapour deposition (CVD). We report a correlation between the growth rate of h-BN and the orientation of the nickel grains. The surface of the nickel (Ni) foil was first polished by electrochemical polishing (ECP) and subsequently annealed in hydrogen at atmospheric pressure to suppress the effect of the surface morphology. Atmospheric annealing with hydrogen reduced the nucleation sites of h-BN, which induced a large crystal size mainly grown from the grain boundary with few other nucleation sites in the Ni foil. A higher growth rate was observed from the Ni grains that had the {110} or {100} orientation due to their higher surface energy. PMID- 26156070 TI - Mobility and biodegradability of an imidazolium based ionic liquid in soil and soil amended with waste sewage sludge. AB - Sorption on solids and biodegradation are main phenomena that can mitigate the pollution of soil and water by ionic liquids (ILs). ILs sorbed on soil particles become immobilized (temporarily or permanently) which prevents them from spreading into deeper layers of soil or groundwater but which also makes them less bioavailable. In this study we attempt to examine if amendment of soil with waste sludge has a potential to mitigate the transport and enhance biodegradation of ILs using 1-methyl-3-octylimidazolium chloride ([OMIM][Cl]) as an example. We present the results of adsorption test (batch and column) and ultimate biodegradation of [OMIM][Cl] using microbial communities derived from soil. Finally, we combine all of these processes together to examine the fate of [OMIM][Cl] in a continuous column flow-through system in soil amended with waste sewage sludge. Addition of sludge serves two purposes: firstly increasing soil organic matter (formerly proved to facilitate retardation), and secondly augmenting soil with versatile microbial communities previously shown to successfully degrade ILs. PMID- 26156069 TI - Kv1.3 contains an alternative C-terminal ER exit motif and is recruited into COPII vesicles by Sec24a. AB - BACKGROUND: Potassium channels play a fundamental role in resetting the resting membrane potential of excitable cells. Determining the intracellular trafficking and localization mechanisms of potassium channels provides a platform to fully characterize their maturation and functionality. Previous investigations have discovered residues or motifs that exist in their primary structure, which directly promote anterograde trafficking of nascent potassium channels. Recently, a non-conical di-acidic motif (E483/484) has been discovered in the C-terminus of the mammalian homologue of the Shaker voltage-gated potassium channel subfamily member 3 (Kv1.3), and was shown to disrupt the anterograde trafficking of Kv1.3. RESULTS: We have further investigated the intracellular trafficking requirements of Kv1.3 both in vivo and in vitro. First, three alternative C-terminal acidic residues, E443, E445, E447 were probed for their involvement within the early secretory pathway of Kv1.3. Single point (E443A, E445A, and E447A) and double point (E443A-E445A, E445A-E447A) mutations exhibited no significant changes in their endoplasmic reticulum (ER) retention. The triple point mutant E443A-E445A E447A displayed a modest ER retention while deletion of the C-terminus showed dramatic ER retention. Second, we demonstrate in vivo the requirement for the Sec24a isoform to confer anterograde trafficking using a siRNA knockdown assay. Third, we show in vitro the association of recombinantly expressed Kv1.3 and Sec24a proteins. CONCLUSION: These results expand upon previous studies aimed at deciphering the Kv1.3 secretory trafficking mechanisms and further show in vitro evidence of the association between Kv1.3 and the COPII cargo adaptor subunit isoform Sec24a. PMID- 26156072 TI - Rethinking governance for trade and health. PMID- 26156071 TI - Systemic connective tissue features in women with fibromuscular dysplasia. AB - Fibromuscular dysplasia (FMD) is a non-atherosclerotic disease associated with hypertension, headache, dissection, stroke, and aneurysm. The etiology is unknown but hypothesized to involve genetic and environmental components. Previous studies suggest a possible overlap of FMD with other connective tissue diseases that present with dissections and aneurysms. The aim of this study was to investigate the prevalence of connective tissue physical features in FMD. A total of 142 FMD patients were consecutively enrolled at a single referral center (97.9% female, 92.1% of whom had multifocal FMD). Data are reported for 139 female patients. Moderately severe myopia (29.1%), high palate (33.1%), dental crowding (29.7%), and early-onset arthritis (15.6%) were prevalent features. Classic connective features such as hypertelorism, cleft palate, and hypermobility were uncommon. The frequency of systemic connective tissue features was compared between FMD patients with a high vascular risk profile (having had ?1 dissection and/or ?2 aneurysms) and those with a standard vascular risk profile. A history of spontaneous pneumothorax (5.9% high risk vs 0% standard risk) and atrophic scarring (17.6% high risk vs 6.8% standard risk) were significantly more prevalent in the high risk group, p<0.05. High palate was observed in 43.1% of the high risk group versus 27.3% in the standard risk group, p=0.055. In conclusion, in a cohort of women with FMD, there was a prevalence of moderately severe myopia, high palate, dental crowding, and early-onset osteoarthritis. However, a characteristic phenotype was not discovered. Several connective tissue features such as high palate and pneumothorax were more prominent among FMD patients with a high vascular risk profile. PMID- 26156073 TI - Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial. AB - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment of renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double blind, placebo-controlled trial are presented. METHODS: Following favorable results from the primary analysis (data cutoff 30 June 2011) of the EXIST-2 trial, patients still receiving study treatment were allowed to enter an open label extension. Everolimus was initiated at 10 mg once daily and titrated based on tolerability. The primary outcome was angiomyolipoma response rate (>= 50% reduction from baseline in target lesion volumes). Safety was a secondary endpoint. RESULTS: As of the cutoff date (1 May 2013), 112 patients had received everolimus, and the response rate in 107 patients with angiomyolipoma (median duration of medication exposure of 28.9 months) was 54%. The proportion of patients achieving angiomyolipoma reductions of >= 30% and >= 50% increased over time, reaching 81.6% (62/76) and 64.5% (49/76), respectively, by Week 96. No everolimus-treated patients experienced renal bleeding. The long-term safety profile was consistent with previous reports; adverse events (AEs) were mostly Grade 1/2, and there were no new safety issues. The frequency of emerging AEs and severe AEs lessened over time. CONCLUSIONS: Longer term everolimus treatment appeared safe and effective in patients with TSC- or sporadic LAM-associated renal angiomyolipoma not requiring surgical intervention. Continued reduction in angiomyolipoma volume was demonstrated, and there was no angiomyolipoma-related bleeding; AEs were predictable and generally manageable. TRIAL REGISTRATION: clinicaltrialsgov identifier: NCT00790400 (http://clinicaltrials.gov/ct2/show/NCT00790400). PMID- 26156076 TI - Migraine aura symptoms: Duration, succession and temporal relationship to headache. AB - BACKGROUND: As there are no biological markers, a detailed description of symptoms, particularly temporal characteristics, is crucial when diagnosing migraine aura. Hitherto these temporal aspects have not been studied in detail. METHODS: We conducted a prospective diary-aided study of the duration and the succession of aura symptoms and their temporal relationship with headache. RESULTS: Fifty-four patients completed the study recording in a diary the characteristics of three consecutive auras ( ITALIC! n = 162 auras). The median duration of visual, sensory and dysphasic symptoms were 30, 20 and 20 minutes, respectively. Visual symptoms lasted for more than one hour in 14% of auras ( ITALIC! n = 158), sensory symptoms in 21% of auras ( ITALIC! n = 52), and dysphasic symptoms in 17% of auras ( ITALIC! n = 18). Twenty-six percent of patients had at least one aura out of three with one symptom lasting for more than one hour. In aura with multiple symptoms the subsequent symptom, second versus first one or third versus second, might either start simultaneously (34 and 18%), during (37 and 55%), with the end (5 and 9%), or after (24 and 18%) the previous aura symptom. The headache phase started before the aura (9%), simultaneously with the onset of aura (14%), during the aura (26%), simultaneously with the end of aura (15%) or after the end of aura (36%). CONCLUSION: We provide data to suggest that symptoms may last longer than one hour in a relevant proportion of auras or migraine with aura patients, and that there is a high variability of scenarios in terms of time relationship among aura symptoms and between aura and headache. PMID- 26156074 TI - IFN-gamma promotes tau phosphorylation without affecting mature tangles. AB - Inflammatory activation precedes and correlates with accumulating tau lesions in Alzheimer's disease and tauopathies. However, the relationship between neuroinflammation and etiology of pathologic tau remains elusive. To evaluate whether inflammatory signaling may promote or accelerate neurofibrillary tangle pathology, we explored the effect of recombinant adeno-associated virus (rAAV) mediated overexpression of a master inflammatory cytokine, IFN-gamma, on tau phosphorylation. In initial studies in primary neuroglial cultures, rAAV-mediated expression of IFN-gamma did not alter endogenous tau production or paired helical filament tau phosphorylation. Next, we tested the effect of rAAV-mediated expression of IFN-gamma in the brains of 2 mouse models of tauopathy: JNPL3 and rTg4510. In both models, IFN-gamma increased 1) signal transducer and activator of transcription 1 levels and gliosis, and 2) hyperphosphorylation and conformational alterations of soluble tau compared with control cohorts. However, sarkosyl-insoluble phosphorylated tau levels and ubiquitin staining were unaltered in the IFN-gamma cohorts. Notably, IFN-gamma-induced tau hyperphosphorylation was associated with release of the inhibitory effect of glycogen synthase kinase 3beta function by decreasing Ser9 phosphorylation. Our data suggest that type II IFN signaling can promote tau phosphorylation by modulating cellular kinase activity, though this is insufficient in accelerating neuritic tangle pathology. PMID- 26156078 TI - Ablative therapies for lung metastases: a need to acknowledge the efficacy and toxicity of stereotactic ablative body radiotherapy. PMID- 26156077 TI - Increased palmitate intake: higher acylcarnitine concentrations without impaired progression of beta-oxidation. AB - Palmitic acid (PA) is associated with higher blood concentrations of medium-chain acylcarnitines (MCACs), and we hypothesized that PA may inhibit progression of FA beta-oxidation. Using a cross-over design, 17 adults were fed high PA (HPA) and low PA/high oleic acid (HOA) diets, each for 3 weeks. The [1-(13)C]PA and [13 (13)C]PA tracers were administered with food in random order with each diet, and we assessed PA oxidation (PA OX) and serum AC concentration to determine whether a higher PA intake promoted incomplete PA OX. Dietary PA was completely oxidized during the HOA diet, but only about 40% was oxidized during the HPA diet. The [13 (13)C]PA/[1-(13)C]PA ratio of PA OX had an approximate value of 1.0 for either diet, but the ratio of the serum concentrations of MCACs to long-chain ACs (LCACs) was significantly higher during the HPA diet. Thus, direct measurement of PA OX did not confirm that the HPA diet caused incomplete PA OX, despite the modest, but statistically significant, increase in the ratio of MCACs to LCACs in blood. PMID- 26156080 TI - A case of nontraumatic gas gangrene in a common marmoset (Callithrix jacchus). AB - The common marmoset is widely used in neuroscience and regenerative medicine research. However, information concerning common marmoset disorders, particularly infectious diseases, is scarce. Here, we report a case of a female common marmoset that died suddenly due to gas gangrene. The animal presented with gaseous abdominal distention at postmortem, and Clostridium perfringens type A was isolated from several tissues. Vacuoles, a Gram-positive bacteremia and intravascular hemolysis were observed microscopically in the muscles, liver and lungs. On the basis of these findings, we diagnosed nontraumatic gas gangrene caused by Clostridium perfringens type A in this common marmoset. PMID- 26156079 TI - Expression and significance of CHIP in canine mammary gland tumors. AB - CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several oncogenic proteins. The expression of CHIP is frequently lower in human breast cancer than in normal breast tissue. However, the expression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. We investigated the potential correlation between CHIP expression and mammary gland tumor prognosis in female dogs. CHIP expression was measured in 54 dogs by immunohistochemistry and real-time RT-PCR. CHIP protein expression was significantly correlated with the histopathological diagnosis, outcome of disease and tumor classification. The transcriptional level of CHIP was significantly higher in normal tissues (P=0.001) and benign tumors (P=0.009) than it in malignant tumors. CHIP protein expression was significantly correlated with the transcriptional level of CHIP (P=0.0102). The log-rank test survival curves indicated that patients with low expression of CHIP had shorter overall periods of survival than those with higher CHIP protein expression (P=0.050). Our data suggest that CHIP may play an important role in the formation and development of CMGTs and serve as a valuable prognostic marker and potential target for genetic therapy. PMID- 26156081 TI - Right or Left Traumatic Pericardial Rupture: Report of a Thought-Provoking Case. AB - A 62-yr-old man was transferred to our institution with blunt chest trauma after being pinched between a car and a wall. Chest computed tomography revealed left sided rib fractures, bilateral pneumothorax, and pneumopericardium, but no displacement of the heart. The pneumopericardium caused us to suspect a tear in the pericardium. Since the left pneumothorax was slightly more marked than the right, we planned a left-sided thoracoscopic exploration. As a result, a right sided pericardial rupture was found and repaired under thoracotomy. It was difficult to judge the injured side of the pericardial tear. We learned a valuable lesson from this case: The extent of pleural air may be, but is not always, reliable for identification of the injured side of a pericardial rupture. Direct observation of the pleural space using a thoracoscope is necessary for definitive diagnosis. PMID- 26156082 TI - Organic Materials for Time-Temperature Integrator Devices. AB - Time-temperature integrators (TTIs) are devices capable of recording the thermal history of a system. They have an enormous impact in the food and pharmaceutical industries. TTIs exploit several irreversible thermally activated transitions such as recrystallization, dewetting, smoothening, chemical decomposition, and polymorphic transitions, usually considered drawbacks for many technological applications. The aim of this article is to sensitize research groups working in organic synthesis and surface science toward TTI devices, enlarging the prospects of many new materials. We reviewed the principal applications highlighting the need and criticisms of TTIs, which offer a new opportunity for the development of many materials. PMID- 26156083 TI - Childhood adversity and psychosis: generalised or specific effects? AB - BACKGROUND: This study examines relationships between childhood adversity and the presence of characteristic symptoms of schizophrenia. It was hypothesised that total adversity exposures would be significantly higher in individuals exhibiting these symptoms relative to patients without. Recent proposals that differential associations exist between specific psychotic symptoms and specific adversities was also tested, namely: sexual abuse and hallucinations, physical abuse and delusions, and fostering/adoption and delusions. METHOD: Data were collected through auditing 251 randomly selected medical records, drawn from adult patients in New Zealand community mental health centres. Information was extracted on presence and subtype of psychotic symptoms and exposure to ten types of childhood adversity, including five types of abuse and neglect. RESULTS: Adversity exposure was significantly higher in patients experiencing hallucinations in general, voice hearing, command hallucinations, visions, delusions in general, paranoid delusions and negative symptoms than in patients without these symptoms. There was no difference in adversity exposure in patients with and without tactile/olfactory hallucinations, grandiose delusions or thought disorder. Indication of a dose-response relationship was detected, in that total number of adversities significantly predicted total number of psychotic symptoms. Although fostering/adoption was associated with paranoid delusions, the hypothesised specificity between sexual abuse and hallucinations, and physical abuse and delusions, was not found. The two adversities showing the largest number of associations with psychotic symptoms were poverty and being fostered/adopted. CONCLUSIONS: The current data are consistent with a model of global and cumulative adversity, in which multiple exposures may intensify psychosis risk beyond the impact of single events. Implications for clinical intervention are discussed. PMID- 26156084 TI - Retinoid-related orphan receptor gamma t modulators: comparison of Glenmark's me too patent application (WO2015008234) with the originator application from Merck Sharp and Dohme (WO2012106995). AB - Retinoic acid receptor-related orphan nuclear receptor gamma t (RORgammat) is a key transcription factor for the development of TH17 cells. Inhibiting RORgammat activity is thought to be beneficial in targeting a variety of inflammatory and autoimmune disorders. In their patent application WO2015008234, Glenmark applied a scaffold-hop approach regarding to the originator application from Merck Sharp & Dohme (WO2012106995): a 6-membered annelated aromatic moiety is replaced by an annelated 5-membered heteroaryl (exemplified and claimed is however only thiophene), resulting in potent RORgammat inverse agonists with a thieno[3,2 b]pyrrole or thieno[3,2-c]pyrazole core. Based on the patent disclosure, the novelty and utility of these me-too compounds is discussed. PMID- 26156085 TI - DNA Brushing Shoulders: Targeted Looping and Scanning of Large DNA Strands. AB - We present a nanofluidic device for targeted manipulations in the quarternary structure of single DNA molecules. We demonstrate the folding and unfolding of hairpin-shaped regions, similar to chromatin loops. These loops are stable for minutes at nanochannel junctions. We demonstrate continuous scanning of two DNA segments that occupy a common nanovolume. We present a model governing the stability of loop folds and discuss how the system achieves specific DNA configurations without operator intervention. PMID- 26156086 TI - Comparison of breast simultaneous integrated boost (SIB) radiotherapy techniques. AB - PURPOSE: To dosimetrically evaluate different breast SIB techniques with respect to target coverage and organs at risk (OARs) doses. METHODS: Four IMRT techniques were compared in 12 patients. Three techniques employ tangential whole breast irradiation with either two coplanar fields (T-2F), or four non-coplanar fields (T-NC), or one Volumetric Modulated Arc Therapy (T-VMAT) for the boost volume. The fourth technique is a fully-modulated VMAT technique (f-VMAT). Dosimetric parameters were compared for the boost and breast target volumes as well as OARs. Delivery efficiency was analysed based on number of monitor units (MUs) and estimated delivery time. RESULTS: T-VMAT and f-VMAT ranked highest with respect to integral assessment of boost and breast treatment quality measures. T-VMAT significantly outperformed f-VMAT with respect to ipsi-lateral lung and left sided patients' heart volumes >= 5 Gy (35 % +/- 5 % vs. 52 % +/- 6 % and 11 % +/- 5 % vs. 22 % +/- 6 %, respectively). f-VMAT significantly outperformed T-VMAT with respect to ipsi-lateral lung volume >= 20 Gy (13 % +/- 2 % vs. 15 % +/- 3 %) and heart volume >= 30 Gy in left breast cancer (0 % +/- 0 % vs. 1 % +/- 1 %). T VMAT and f-VMAT needed 442 +/- 58 and 1016 +/- 152 MUs, respectively. CONCLUSIONS: The hybrid T-VMAT is considered the technique of choice due to its balance of quality, efficiency and dose to OARs. PMID- 26156088 TI - Au@TiO2 yolk-shell hollow spheres for plasmon-induced photocatalytic reduction of CO2 to solar fuel via a local electromagnetic field. AB - An electric field in a photocatalytic system consisting of Au@TiO2 yolk-shell hollow spheres is created to enhance the generation of electron-hole pairs and remit the charge-carrier recombination. Local surface plasmon resonance (LSPR) mediated local electromagnetic field nearby Au nanoparticles cannot only enhance the local generation and subsequent separation of electron-hole pairs in TiO2 shells to improve the photoreduction yield of CO2, but also facilitate chemical reactions involving multiple e(-)/H(+) transfer processes to allow the formation of high-grade carbon species (C2H6), which was rarely observed in precedent CO2 photocatalytic reduction systems. The work may provide a new viewpoint for designing photocatalysts for artificial photosynthesis involving multiple reactions. PMID- 26156087 TI - Neuropathologic analysis of Tyr69His TTR variant meningovascular amyloidosis with dementia. AB - Transthyretin/TTR gene mutations usually cause systemic amyloidotic diseases. Few TTR variants preferentially affect the central nervous system, manifesting as oculoleptomeningeal amyloidosis. Patients with TTR meningovascular amyloidosis often show dementia, however the neuropathologic features of dementia in these cases have not been elucidated. We report the neuropathologic findings from a brain autopsy of a 72-year-old man with the rare Tyr69His (Y69H) TTR gene variant, dementia and ataxia. Severe amyloid deposits were observed in the leptomeninges and in a subpial and subependymal distribution. Mass spectrometry analysis demonstrated that the amyloid deposits were comprised of over 80 % of the variant TTR. TTR was undetectable by mass spectrometry in the neocortex subjacent to the subpial amyloid deposits. Subpial TTR amyloid deposits were associated with brisk superficial reactive gliosis and siderosis in the neocortex and cerebellar cortex. Subependymal TTR amyloid deposits were associated with subjacent myelin pallor in the hippocampal outflow tract structures including the alveus, fimbria and fornix. Phospho-tau immunostains demonstrated transentorhinal stage neurofibrillary degeneration (Braak stage II) which, in the absence of neocortical amyloid-beta and neuritic plaques, was indicative of primary age related tauopathy (PART). However, distinctive phospho-tau aggregates were observed subjacent to the subpial TTR amyloid deposits in all regions of the neocortex, including the primary motor and striate cortices, suggesting a potential link between TTR amyloid and neocortical tauopathy. Our report reveals novel insights into the potential neuropathologic substrates of dementia in variant TTR amyloidosis that need to be investigated in larger autopsy series. PMID- 26156089 TI - Genomic Study Divides Up Cutaneous Melanomas. PMID- 26156090 TI - New Insight into Mucinous Ovarian Cancer. PMID- 26156091 TI - Device Captures CTC Clusters in Blood. PMID- 26156094 TI - Vertical distribution of Fe and Fe(III)-reducing bacteria in the sediments of Lake Donghu, China. AB - In lake sediments, iron (Fe) is the most versatile element, and the redox cycling of Fe has a wide influence on the biogeochemical cycling of organic and inorganic substances. The aim of the present study was to analyze the vertical distribution of Fe and Fe(III)-reducing bacteria (FeRB) in the surface sediment (30 cm) of Lake Donghu, China. At the 3 sites we surveyed, FeRB and Fe(II)-oxidizing bacteria (FeOB) coexisted in anoxic sediments. Geobacter-related FeRB accounted for 5%-31% of the total Bacteria, while Gallionella-related FeOB accounted for only 0.1%-1.3%. A significant correlation between the relative abundance of poorly crystalline Fe and Geobacter spp. suggested that poorly crystalline Fe favored microbial Fe(III) reduction. Poorly crystalline Fe and Geobacter spp. were significantly associated with solid-phase Fe(II) and total inorganic phosphorus levels. Pore water Fe(II) concentrations negatively correlated with NO3(-) at all sites. We concluded that Geobacter spp. were abundant in the sediments of Lake Donghu, and the redox of Fe might participate in the cycling of nitrogen and phosphorus in sediments. These observations provided insight into the roles of microbial Fe cycling in lake sediments. PMID- 26156092 TI - Focal segmental glomerulosclerosis: molecular genetics and targeted therapies. AB - Recent advances show that human focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy caused by podocyte-specific gene mutations including NPHS1, NPHS2, WT-1, LAMB2, CD2AP, TRPC6, ACTN4 and INF2. This review focuses on genes discovered in the investigation of complex FSGS pathomechanisms that may have implications for the current FSGS classification scheme. It also recounts recent recommendations for clinical management of FSGS based on translational studies and clinical trials. The advent of next-generation sequencing promises to provide nephrologists with rapid and novel approaches for the diagnosis and treatment of FSGS. A stratified and targeted approach based on the underlying molecular defects is evolving. PMID- 26156095 TI - Social inequality and age-specific gender differences in overweight and perception of overweight among Swedish children and adolescents: a cross sectional study. AB - BACKGROUND: Overweight among children and adolescents related to social inequality, as well as age and gender differences, may contribute to poor self image, thereby raising important public health concerns. This study explores social inequality in relation to overweight and perception of overweight among 263 boys and girls, age 7 to 17, in Vaxjo, Sweden. METHODS: Data were obtained through a questionnaire and from physical measurements of height, weight and waist circumference [WC]. To assess social, age and gender differences in relation to overweight, the independent sample t- and chi-square tests were used, while logistic regression modeling was used to study determinants for perception of overweight. RESULTS: Social inequality and gender differences as they relate to high ISO-BMI [Body Mass Index for children] and WC were associated with low maternal socioeconomic status [SES] among boys < 13 years [mean age = 10.4; n = 65] and with low paternal education level among boys >= 13 years [mean age = 15.0; n = 39] [p < 0.05]. One suggested explanation for this finding is maternal impact on boys during childhood and the influence of the father as a role model for adolescent boys. The only association found among girls was between high ISO BMI in girls >= 13 years [mean age = 15.0; n = 74] and low paternal occupational status. Concerning perception of overweight, age and gender differences were found, but social inequality was not the case. Among boys and girls < 13 years, perception of overweight increased only when overweight was actually present according to BMI or WC [p < 0.01]. Girls >= 13 years [mean age = 15.0] were more likely to unrealistically perceive themselves as overweight or "too fat," despite factual measurements to the contrary, than boys [p < 0.05] and girls < 13 years [mean age = 10.4; n = 83] [p < 0.001]. CONCLUSIONS: The association between social inequality and overweight in adolescence in this study is age- and gender specific. Gender differences, especially in perception of overweight, tend to increase with age, indicating that adolescence is a crucial period. When planning interventions to prevent overweight and obesity among children and adolescents, parental SES as well as age and gender-specific differences in social norms and perception of body weight status should be taken into account. PMID- 26156096 TI - The Prevalence and Characteristics of Emergency Medicine Patient Use of New Media. AB - BACKGROUND: Little is known about "new media" use, defined as media content created or consumed on demand on an electronic device, by patients in emergency department (ED) settings. The application of this technology has the potential to enhance health care beyond the index visit. OBJECTIVE: The objectives are to determine the prevalence and characteristics of ED patients' use of new media and to then define and identify the potential of new media to transcend health care barriers and improve the public's health. METHODS: Face-to-face, cross-sectional surveys in Spanish and English were given to 5,994 patients who were sequentially enrolled from July 12 to August 30, 2012. Data were collected from across a Southern Connecticut health care system's 3 high-volume EDs for 24 hours a day, 7 days a week for 6 weeks. The EDs were part of an urban academic teaching hospital, an urban community hospital, and an academic affiliate hospital. RESULTS: A total of 5,994 (89% response rate) ED patients reported identical ownership of cell phones (85%, P<.001) and smartphones (51%, P<.001) that were used for calling (99%, P<.001). The older the patient, however, the less likely it was that the patient used the phone for texting (96% vs 16%, P<.001). Income was positively associated with smartphone ownership (P<.001) and the use of health apps (P>.05) and personal health records (P<.001). Ownership of iPhones compared to Android phones were similar (44% vs 45%, P<.05). Race and ethnicity played a significant role in texting and smartphone ownership, with Hispanics reporting the highest rates of 79% and 56%, respectively, followed by black non Hispanics at 77% and 54%, respectively, and white non-Hispanics at 65% and 42%, respectively (P<.05). CONCLUSIONS: There is a critical mass of ED patients who use new media. Older persons are less comfortable texting and using smartphone apps. Income status has a positive relationship with smartphone ownership and use of smartphone apps. Regardless of income, however, texting and ownership of smartphones was highest for Latinos and black non-Latinos. These findings have implications for expanding health care beyond the ED visit through the use of cell phones, smartphones, texting, the Internet, and health care apps to improve the health of the public. PMID- 26156097 TI - Functional outcomes and recanalization rates of stent retrievers in acute ischaemic stroke: A systematic review and meta-analysis. AB - BACKGROUND AND PURPOSE: Intra-arterial therapy for acute ischaemic stroke has evolved rapidly in the last few years. Stent retrievers have now replaced 'first generation' devices, which have been the principle devices tested in stroke trials.Our aims were to determine the rates of successful recanalization and functional independence in acute stroke patients treated with stent retrievers. We also sought to assess the safety outcomes of stent retrievers by assessing the rates of mortality and intra-cranial haemorrhage. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of studies which utilized stent retrievers as sole treatment or as part of a multi-modal approach in acute ischaemic stroke. RESULTS: We identified 20 eligible studies: 17 on Solitaire (ev3/Covidien, Irvine, California, USA) (n = 762) and three on Trevo (Stryker, Kalamazoo, Michigan, USA) (n = 210). The mean age of participants was 66.8 (range 62.1-73.0) years and the M:F ratio was 1.1:1. The average stroke severity score (National Institutes of Health Stroke Scale (NIHSS)) at presentation was 17.2. The weighted mean symptom onset to arterial puncture and procedural duration were 265.4 minutes and 54.8 minutes, respectively.Successful recanalization was achieved in 84.5% of patients with a weighted mean of 2.0 stent retriever passes. Independent functional outcome was achieved in 51.2% and the mortality rate was 16.8%. CONCLUSION: Stent retrievers have the potential to achieve a high rate of recanalization and functional independence whilst being relatively safe. They should be assessed in well-designed randomized controlled trials to determine their efficacy and assess whether they compare favourably with 'standard treatment' in stroke. PMID- 26156098 TI - Prognostic value of coronary computed tomography angiography in diabetic patients without chest pain syndrome. AB - AIMS: Diabetic patients with coronary artery disease (CAD) are often free of chest pain syndrome. A useful modality for non-invasive assessment of CAD is coronary computed tomography angiography (CTA). However, the prognostic value of CAD on coronary CTA in diabetic patients without chest pain syndrome is relatively unknown. Therefore, the aim was to investigate the long-term prognostic value of coronary CTA in a large population diabetic patients without chest pain syndrome. METHODS: Between 2005 and 2013, 525 diabetic patients without chest pain syndrome were prospectively included to undergo coronary artery calcium (CAC)-scoring followed by coronary CTA. During follow-up, the composite endpoint of all-cause mortality, non-fatal myocardial infarction (MI), and late revascularization (>90 days) was registered. RESULTS: In total, CAC scoring was performed in 410 patients and coronary CTA in 444 patients (431 interpretable). After median follow-up of 5.0 (IQR 2.7-6.5) years, the composite endpoint occurred in 65 (14%) patients. Coronary CTA demonstrated a high prevalence of CAD (85%), mostly non-obstructive CAD (51%). Furthermore, patients with a normal CTA had an excellent prognosis (event-rate 3%). An incremental increase in event-rate was observed with increasing CAC-risk category or coronary stenosis severity. Finally, obstructive (50-70%) or severe CAD (>70%) was independently predictive of events (HR 11.10 [2.52;48.79] (P = .001), HR 15.16 [3.01;76.36] (P = .001)). Obstructive (50-70%) or severe CAD (>70%) provided increased value over baseline risk factors. CONCLUSION: Coronary CTA provided prognostic value in diabetic patients without chest pain syndrome. Most importantly, the prognosis of patients with a normal CTA was excellent. PMID- 26156099 TI - Measurement of ampicillin residue levels in chicken eggs during and after medicated feed administration by LC-MS/MS. AB - A simple and sensitive LC-MS/MS method was developed and validated for the determination of ampicillin (ABPC) in chicken eggs. Residues were extracted by reverse-phase solid-phase extraction. Chromatographic separation was performed using a reverse-phase column with an elution gradient. The limits of detection and quantification were 0.01 and 0.1 ng g(-1), respectively. For the 0.1-50 ng g( 1) concentration range, mean recovery and accuracy values were 93.9-98.5% and 100.2-118.0%, respectively. ABPC residue concentrations in eggs before, during and after 7 days of medicated feeding of maximum dosage (40 mg kg(-1) body weight day(-1)) of ABPC were determined with the LC-MS/MS method. The maximum concentration of ABPC in eggs was 3.6 +/- 1.7 ng g(-1) (mean +/- SD) on the last day of the administration period. Residue concentrations of ABPC in eggs during and after ABPC administration were not over the Japanese maximum residue limit of 0.01 mg kg(-1). PMID- 26156100 TI - What has been overlooked on study of Chinese materia medica in the West? AB - Chinese materia medica (CMM), including Chinese herbal, animal, and mineral medicine, has been widely researched in the past century for their biological and pharmacological activities. However, their mechanism and clinical efficacy studies did not always give expected results. For example, the most commonly used Chinese herb for menstrual disorders, Radix Angelicae sinensis, showed neither estrogenic nor progesteronic activity in laboratory and clinical studies. Its efficacy should not be denied simply based on such results, because it is mostly used together with other herbs in formulae. Moreover, its regulation on menstruation may take effect through other mechanisms, such as regulation of blood circulation. The key difference of Chinese medicine (CM) from conventional medicine is its unique holistic view on human body and diseases. CMM is mostly applied in clinic in the form of formulae. Study on individual CMM, simply using methods for development of conventional drugs, is unable to thoroughly reveal the power of CMM formulae. The reason may partly result from improper design due to the lack understanding about application principle of CMMs in CM, and/or to current lack of knowledge about the causes of some symptoms and diseases. This paper will introduce the importance of qi and blood in CM etiology and pathology, Zheng differentiation, formulation of CMMs, and explain why one formula can treat different diseases and one disease can be treated with different formulae. Examples in the paper will demonstrate that proper studies on Zheng and its corresponding clinically proven formulae could help scientists find new direction to explain and treat symptoms and diseases that so far modern medicine has been unable to, provided that the designer properly understands CM theories, etiology and pathology of CM, as well as modern medicine. Strategy suggestions about research methods for CMM and its formulae will be given at the end. PMID- 26156102 TI - Oral health-related quality of life after prosthetic rehabilitation: a longitudinal study with the OHIP questionnaire. AB - BACKGROUND: Aspects of oral health related quality of life (OHRQoL) attracted an increased attention recently. OBJECTIVE: The aim of the study was to assess self reported oral health related quality of life (OHRQoL) among patients requiring prosthetic rehabilitation and to determine the rate of improvement 1 month and 6 12 months after therapy. In addition, effect of age, gender, oral health indicators and denture types before treatment were assessed on OHRQoL as evaluated and reported by the patients. METHODS: Hungarian version of OHIP-49 (OHIP-49-H) questionnaire was completed before oral rehabilitation (T0-phase) by 389 patients undergoing prosthetic replacement. After 1 month (T1-phase) and 6-12 months (T2-phase) recall periods 235 and 92 patients completed the questionnaire. The median interquartile range (IQR) values of the total OHIP-49-H score were calculated for T0-, T1- and T2-phases. Reliability of the questionnaire was checked by Cronbach's statistics. Age, gender, oral health indicators and denture types of patients before and after treatment were recorded and treatment associated changes in OHRQoL were evaluated. RESULTS: The study demonstrated the excellent reliability and internal consistency of OHIP-49-H by a high and narrow range of Cronbach's alpha value (0.81-0.93). A median OHIP-49-H score of 52; IQR = 25-83 demonstrated a poor OHRQoL on first admission. Decreasing median total OHIP-49-H scores 1 month (24; IQR = 9-51; p < 0.001) and 6-12 months (20; IQR = 7 37; p = 0,055) after therapy indicated an improvement of OHRQoL. Patients' age and CPI value assessed before treatment proved to be significant factors of OHRQoL. CONCLUSIONS: Here we presented representative data about self-assessed OHRQoL of patients requiring prosthetic treatment from Hungary using OHIP-49-H questionnaire. The results demonstrated that the restoration of oral health was associated with an improvement in patients' OHRQoL. According to the demographical and T0 phase clinical status, the treatment was more effective in the respect of OHIP-49-H score improvement among females (than among males), among younger (than among more aged), and among patients with more serious CPI assessed at T0. The type of prosthetic interventions did not exert a significant effect on total OHIP-49-H score, suggesting that the improvement in OHRQoL is independent from the type of denture applied. PMID- 26156101 TI - Development of a training programme for home health care workers to promote preventive activities focused on a healthy lifestyle: an intervention mapping approach. AB - BACKGROUND: Lifestyle is an important aspect in maintaining good health in older adults, and home health care (HHC) workers can play an important role in promoting a healthy lifestyle. However, there is limited evidence in the literature regarding how to develop an effective training programme to improve the physical activity level and fruit and vegetable consumption of older adults within a HHC setting. The aim of this paper is to describe how Intervention Mapping (IM) was used to develop a training programme to promote preventive activities of HHC workers relating to the physical activity and fruit and vegetable intake of older adults living at home. METHODS: IM, a systematic theory and evidence-based approach was used to develop, implement and evaluate the training programme. This entailed a literature search, a survey, semi-structured interviews and consultation with HHC workers and various field experts, and a pilot training session. RESULTS: The determinants associated with the provision of preventive activities were identified, and an overview was created of those objectives, matching methods and practical applications that could influence these determinants. The performance objectives for the HHC workers were early detection and monitoring, promoting a healthy lifestyle, informing colleagues, continuing allocated preventive activities and referring to other experts and facilities. Findings were translated into a comprehensive training programme for HHC workers focused on motivating older adults to adopt and maintain a healthier lifestyle. CONCLUSIONS: IM was a useful tool in the development of a theory-based training programme to promote preventive activities by HHC workers relating to fruit and vegetable intake and physical activity of older adults. PMID- 26156104 TI - Antiherpes evaluation of soybean isoflavonoids. AB - The antiviral effects of soybean isoflavonoids have been investigated recently, especially those of genistein. It has been reported that this isoflavone is able to inhibit herpes simplex virus (HSV) replication, which is associated with skin and epithelial mucosa infections. The treatment of these infections with antiherpes drugs has resulted in the emergence of resistant viral strains. Based on this evidence, the aim of this study was to investigate the anti-HSV effects of soybean isoflavonoids: daidzein, genistein, glycitein, and coumestrol. Genistein and coumestrol inhibited HSV-1 (KOS and 29R strains, which are acyclovir sensitive and acyclovir resistant, respectively) and HSV-2 (333 strain) replication, whereas no antiviral effects were detected for daidzein and glycitein. The mechanisms of action were evaluated by different methodological strategies. Coumestrol affected the early stages of viral infection, and both compounds were able to reduce HSV-1 protein expression, as well as HSV-2 cell-to cell spread. PMID- 26156103 TI - PHDs govern plant development. AB - Posttranslational modifications present in the amino-terminal tails of histones play a pivotal role in the chromatin-mediated regulation of gene expression patterns that control plant developmental transitions. Therefore, the function of protein domains that specifically recognize these histone covalent modifications and recruit chromatin remodeling complexes and the transcriptional machinery to modulate gene expression is essential for a proper control of plant development. Plant HomeoDomain (PHD) motifs act as effectors that can specifically bind a number of histone modifications and mediate the activation or repression of underlying genes. In this review we summarize recent findings that emphasize the crucial role of this versatile family of chromatin "reader" domains in the transcriptional regulation of plant developmental processes such as meiosis and postmeiotic events during pollen maturation, embryo meristem initiation and root development, germination as well as flowering time. PMID- 26156105 TI - Role of angiotensin II in experimental Venezuelan equine encephalitis in rats. AB - Venezuelan equine encephalitis (VEE) is a viral disease transmitted by mosquitoes. The inflammation induced by the VEE virus is associated with a high mortality rate in mice. Angiotensin II (Ang II), a pro-inflammatory molecule, is produced in the normal rat brain. There is no information about the role of this molecule in the inflammatory events occurring during VEE and the effect of inflammation on the mortality rate in VEE-virus-infected rats. This study was designed to determine the role of Ang II in VEE and to analyze the effect of inflammation on mortality in infected rats. Two groups of rats were studied: 1) Virus-infected animals and controls (n = 60) were treated with losartan (a blocker of the Ang II-AT1 receptor) or with pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-kappaB) or left untreated and analyzed for morbidity and mortality. 2) Animals treated using the same protocol (n = 30) were sacrificed at day 4 postinfection and analyzed by immunohistochemistry and histopathology and for cytokine production. Increased expression of Ang II, ICAM-1, ED-1 and cytokines (IL-1alpha, MCP-1, IL-6 and IL-10) in infected animals was observed. The main histopathology findings were dilated capillaries and capillaries with endothelial detachment. Losartan and PDTC reduced the expression of IL-1alpha, MCP-1, and IL-10, and the number of dilated capillaries and capillaries with endothelial detachment. Survival analysis showed that 100% mortality was reached earlier in infected rats treated with losartan (day 14) or PDTC (day 11) than in untreated animals (day 19). These findings suggest that Ang II plays a role in VEE and that brain inflammation is protective against viral infection. PMID- 26156107 TI - Recovery from AKI in the critically ill: potential confounders in the evaluation. AB - PURPOSE: Studies on recovery from acute kidney injury (AKI) in ICU patients yield variable results. We assessed the impact of different recovery definitions, of different exclusion criteria, and of imputing missing baseline creatinine on AKI recovery in a heterogeneous ICU population. METHODS: Secondary analysis of the EPaNIC database. Recovery of kidney function in patients who developed AKI in ICU was assessed at hospital discharge. We studied recovery rates of different AKI stages with different definitions of recovery after inclusion or exclusion of non survivors and in patients with or without chronic kidney disease (CKD). In addition, the impact of imputing missing baseline creatinine was investigated. RESULTS: A total of 1310 AKI patients were studied of which 977 were discharged alive from hospital. Rate of complete recovery (absence of KDIGO criteria) was markedly higher in survivors than in all AKI patients (79.5 vs 67.0%), especially for more severe forms of AKI. For patients with CKD, only the need for renal replacement therapy worsened kidney outcome as compared with no-CKD patients. Using stricter definitions of complete recovery significantly reduced its occurrence. New or worsening CKD occurred in 30% of AKI survivors. In no-CKD patients with available baseline creatinine, using an imputed baseline did not affect recovery. Patients with unavailable baseline creatinine were different from those with known baseline and revealed different recovery patterns. CONCLUSION: These results indicate the need for rigorous description of AKI severity, the included population, definitions, and baseline creatinine handling in reports on AKI recovery. PMID- 26156106 TI - Options and Considerations for Procedural Sedation in Pediatric Imaging. AB - As pediatric imaging capabilities have increased in scope, so have the complexities of providing procedural sedation in this environment. While efforts by many organizations have dramatically increased the safety of pediatric procedural sedation in general, radiology sedation creates several special challenges for the sedation provider. These challenges require implementation of additional safeguards to promote safety during sedation while maintaining effective and efficient care. Multiple agent options are available, and decisions regarding which agent(s) to use should be determined by both patient needs (i.e., developmental capacities, underlying health status, and previous experiences) and procedural needs (i.e., duration, need for immobility, and invasiveness). Increasingly, combinations of agents to either achieve the conditions required or mitigate/counterbalance adverse effects of single agents are being utilized with success. To continue to provide effective imaging sedation, it is incumbent on sedation providers to maintain familiarity with continuing evolutions within radiology environments, as well as comfort and competence with multiple sedation agents/regimens. This review discusses the challenges associated with radiology sedation and outlines various available agent options and combinations, with the intent of facilitating appropriate matching of agent(s) with patient and procedural needs. PMID- 26156108 TI - Effect of a quality improvement program on weaning from mechanical ventilation: a cluster randomized trial. AB - PURPOSE: To evaluate the efficacy of a quality improvement (QI) program for protocol-directed weaning from mechanical ventilation. METHODS: This was a prospective, cluster randomized controlled trial. The study consisted of a baseline phase and a QI phase. Fourteen intensive care units (ICUs) in Beijing, China, were randomized into the QI group and non-QI group. The QI group received a QI program to improve the compliance with protocol-directed weaning during the QI phase. RESULTS: A total of 444 patients were enrolled in the non-QI group (193 for the baseline, 251 for the QI phase) and 440 in the QI group (199 for the baseline, 241 for the QI phase). During the QI phase in the QI group, compared with the non-QI group, total duration of mechanical ventilation decreased from 7.0 to 3.0 days (p = 0.003), the time before the first weaning attempt decreased from 3.63 to 1.96 days (p = 0.003), length of ICU stay decreased from 10.0 to 6.0 days (p = 0.004), length of hospital stay decreased from 23.0 to 19.0 days (p < 0.001). These differences were also significant in the QI group when the QI phase was compared with the baseline phase. In addition, there was a significant reduction in the percentage of mechanical ventilation exceeding 21 days (p = 0.001) when the baseline phase was compared with the QI phase in the QI group. CONCLUSIONS: The QI program involving protocol-directed weaning is associated with beneficial clinical outcomes in mechanically ventilated patients. PMID- 26156109 TI - Central venous catheters and insertion depths: are formulas still up to date? PMID- 26156110 TI - From weaning theory to practice: implementation of a quality improvement program in ICU. PMID- 26156111 TI - Clinical outcomes of primary surgical treatment for acquired vulvar lymphangioma circumscriptum. AB - OBJECTIVE: To assess the clinical outcomes of surgical treatment for acquired vulvar lymphangioma circumscriptum in patients who received radical surgery and/or adjuvant radiation therapy for cervical cancer. METHODS: A retrospective chart review of eight patients was performed to assess the demographic information, chief complaints, treatment modality for cervical cancer, location, and primary treatment modality for vulvar LC, postoperative changes in symptoms, and/or signs, the development of local recurrence and the outcome of patients. RESULTS: All eight patients were previously diagnosed with cervical cancer FIGO clinical stage IA to IIA and received surgery, radiation therapy, or concurrent chemoradiation therapy. Microscopic examination revealed multiple, dilated, D2-40 positive dermal vascular channels containing eosinophilic proteinaceous material, consistent with LC. Most chief complaints showed considerable improvements on assessment at the outpatient clinic after the primary surgery. No patient showed aggravation of symptoms. Two patients developed local recurrences. One patient developed recurrence on the opposite side 13 months after local excision. We performed a second wide local excision. Another patient developed recurrence 47 months after the primary surgery. Since the lesion was very small and localized, we decided to manage it conservatively, but monitor it very closely. The remaining six patients remained free of recurrence. CONCLUSION: It is not easy for gynecologists to have an initial clinical diagnosis of LC, because there are a number of diseases that exhibit similar clinical manifestation to that of vulvar LC. Even if it is diagnosed correctly, local recurrence often occurs. Relevant symptoms associated with LC are not only distressing, but also affect patients' quality of life. Based on our data, we propose that surgical treatment could provide a more long-lasting answer compared to other treatment modalities, since it is beneficial in terms of clinical outcomes. In the future, a long-term follow-up investigation is required to assess the prognosis and to compare the efficacy and side effects of each modality. PMID- 26156112 TI - Multi-Center Study of Diffusion-Weighted Imaging in Coma After Cardiac Arrest. AB - BACKGROUND: The ability to predict outcomes in acutely comatose cardiac arrest survivors is limited. Brain diffusion-weighted magnetic resonance imaging (DWI MRI) has been shown in initial studies to be a simple and effective prognostic tool. This study aimed to determine the predictive value of previously defined DWI MRI thresholds in a multi-center cohort. METHODS: DWI MRIs of comatose post cardiac arrest patients were analyzed in this multi-center retrospective observational study. Poor outcome was defined as failure to regain consciousness within 14 days and/or death during the hospitalization. The apparent diffusion coefficient (ADC) value of each brain voxel was determined. ADC thresholds and brain volumes below each threshold were analyzed for their correlation with outcome. RESULTS: 125 patients were included in the analysis. 33 patients (26%) had a good outcome. An ADC value of less than 650 * 10(-6) mm(2)/s in >=10% of brain volume was highly specific [91% (95% CI 75-98)] and had a good sensitivity [72% (95% CI 61-80)] for predicting poor outcome. This threshold remained an independent predictor of poor outcome in multivariable analysis (p = 0.002). An ADC value of less than 650 * 10(-6) mm(2)/s in >22% of brain volume was needed to achieve 100% specificity for poor outcome. CONCLUSIONS: In patients who remain comatose after cardiac arrest, quantitative DWI MRI findings correlate with early recovery of consciousness. A DWI MRI threshold of 650 * 10(-6) mm(2)/s in >=10% of brain volume can differentiate patients with good versus poor outcome, though in this patient population the threshold was not 100% specific for poor outcome. PMID- 26156113 TI - Differences in Sexual Orientation Diversity and Sexual Fluidity in Attractions Among Gender Minority Adults in Massachusetts. AB - This study characterized sexual orientation identities and sexual fluidity in attractions in a community-based sample of self-identified transgender and gender nonconforming adults in Massachusetts. Participants were recruited in 2013 using bimodel methods (online and in person) to complete a one-time, Web-based quantitative survey that included questions about sexual orientation identity and sexual fluidity. Multivariable logistic regression models estimated adjusted risk ratios (aRRs) and 95% confidence intervals (95% CIs) to examine the correlates of self-reported changes in attractions ever in lifetime among the whole sample (n = 452) and after transition among those who reported social gender transition (n = 205). The sample endorsed diverse sexual orientation identities: 42.7% queer, 19.0% other nonbinary, 15.7% bisexual, 12.2% straight, and 10.4% gay/lesbian. Overall, 58.2% reported having experienced changes in sexual attractions in their lifetime. In adjusted models, trans masculine individuals were more likely than trans feminine individuals to report sexual fluidity in their lifetime (aRR = 1.69; 95% CI = 1.34, 2.12). Among those who transitioned, 64.6% reported a change in attractions posttransition, and trans masculine individuals were less likely than trans feminine individuals to report sexual fluidity (aRR = 0.44; 95% CI = 0.28, 0.69). Heterogeneity of sexual orientation identities and sexual fluidity in attractions are the norm rather than the exception among gender minority people. PMID- 26156115 TI - Chlorophyll a is the crucial redox sensor and transmembrane signal transmitter in the cytochrome b6f complex. Components and mechanisms of state transitions from the hydrophobic mismatch viewpoint. AB - The cytochrome (cyt) b6f complex is involved in the transmembrane redox signaling that triggers state transitions in cyanobacteria and chloroplasts. However, the components and molecular mechanisms are still unclear. In an attempt to solve this long-standing problem, we first focused on the unknown role of a single chlorophyll a (Chla) in cyt b6f with a new approach based on Chla structural properties. Various b6f X-ray crystal structures were analyzed to identify their differences, which correlate with differences in Chla molecular volume. We found that the distance of the Rieske [2Fe-2S] cluster to Chla correlates with the distance between a pair of residues at the Qo-site and the distance between a pair of residues at the opposite membrane side. These correlations were accompanied by the rotation of a key peripheral residue and by changes in the hydrophobic thickness of cyt b6f. Parallel analysis of cyt bc1 crystal structures allowed us to conclude that Chla acts as the crucial redox sensor and transmembrane signal transmitter in b6f for changes in the plastoquinone pool redox state. The hydrophobic mismatch induced by the changed hydrophobic thickness of cyt b6f is the driving force for the structural reorganizations of the photosynthetic apparatus during induction and the progression of state transitions in cyanobacteria and chloroplasts. A mechanism for LHCII kinase activation in chloroplasts is also proposed. Our understanding of the dynamic structural changes in bc-complexes during turnover at the Qo-site and state transitions is augmented by the time-sequence ordering of 56 bc crystal structures. PMID- 26156114 TI - Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): a randomized, monocentric clinical trial. AB - BACKGROUND: Aim of the study was assessment of efficacy and safety of transcutaneous stimulation of the auricular branch of the vagal nerve (t-VNS) in the treatment of chronic migraine. METHODS: A monocentric, randomized, controlled, double-blind study was conducted. After one month of baseline, chronic migraine patients were randomized to receive 25 Hz or 1 Hz stimulation of the sensory vagal area at the left ear by a handhold battery driven stimulator for 4 h/day during 3 months. Headache days per 28 days were compared between baseline and the last month of treatment and the number of days with acute medication was recorded The Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires were used to assess headache-related disability. RESULTS: Of 46 randomized patients, 40 finished the study (per protocol). In the per protocol analysis, patients in the 1 Hz group had a significantly larger reduction in headache days per 28 days than patients in the 25 Hz group (-7.0 +/- 4.6 vs. -3.3 +/- 5.4 days, p = 0.035). 29.4 % of the patients in the 1 Hz group had a >=50 % reduction in headache days vs. 13.3 % in the 25 Hz group. HIT-6 and MIDAS scores were significantly improved in both groups, without group differences. There were no serious treatment-related adverse events. CONCLUSION: Treatment of chronic migraine by t-VNS at 1 Hz was safe and effective. The mean reduction of headache days after 12 weeks of treatment exceeded that reported for other nerve stimulating procedures. PMID- 26156116 TI - Solar-powered oxygen delivery: study protocol for a randomized controlled trial. AB - BACKGROUND: Pneumonia is a leading cause of childhood mortality globally. Oxygen therapy improves survival in children with pneumonia, yet its availability remains limited in many resource-constrained settings where most deaths occur. Solar-powered oxygen delivery could be a sustainable method to improve oxygen delivery in remote areas with restricted access to a supply chain of compressed oxygen cylinders and reliable electrical power. METHODS/DESIGN: This study is a randomized controlled trial (RCT). Solar-powered oxygen delivery systems will be compared to a conventional method (oxygen from cylinders) in patients with hypoxemic respiratory illness. Enrollment will occur at two sites in Uganda: Jinja Regional Referral Hospital and Kambuga District Hospital. The primary outcome will be the length of hospital stay. Secondary study endpoints will be mortality, duration of supplemental oxygen therapy (time to wean oxygen), proportion of patients successfully oxygenated, delivery system failure, cost, system maintenance and convenience. DISCUSSION: The RCT will provide useful data on the feasibility and noninferiority of solar-powered oxygen delivery. This technological innovation uses freely available inputs, the sun and the air, to oxygenate children with pneumonia, and can be applied "off the grid" in remote and/or resource-constrained settings where most pneumonia deaths occur. If proven successful, solar-powered oxygen delivery systems could be scaled up and widely implemented for impact on global child mortality. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT0210086 (date of registration: 27 March, 2014). PMID- 26156118 TI - Stress in crisis managers: evidence from self-report and psychophysiological assessments. AB - Directing disaster operations represents a major professional challenge. Despite its importance to health and professional performance, research on stress in crisis management remains scarce. The present study aimed to investigate self reported stress and psychophysiological stress responses in crisis managers. For this purpose, 30 crisis managers were compared with 30 managers from other disciplines, in terms of self-reported stress, health status and psychophysiological reactivity to crisis-related and non-specific visual and acoustic aversive stimuli and cognitive challenge. Crisis managers reported lower stress levels, a more positive strain-recuperation-balance, greater social resources, reduced physical symptoms, as well as more physical exercise and less alcohol consumption. They exhibited diminished electrodermal and heart rate responses to crisis-related and non-specific stressors. The results indicate reduced stress and physical complaints, diminished psychophysiological stress reactivity, and a healthier life-style in crisis managers. Improved stress resistance may limit vulnerability to stress-related performance decline and facilitate preparedness for major incidents. PMID- 26156119 TI - Social support buffering of the relation between low income and elevated blood pressure in at-risk African-American adults. AB - Socioeconomic disadvantage has been linked to elevated blood pressure (BP), and the purpose of this study was to assess whether interpersonal social supports buffer these adverse relations in African-American adults. In three communities matched demographically, a subsample of participants (N = 204) of the Positive Action for Today's Health trial provided measures of perceived social support, annual household income, and BP. Multiple regression analyses with cross-product interactions were conducted using follow-up data. The sample had a mean age of 52.8 years (SD = 15.1), and was predominantly female (66 %) with a high body mass index (M = 33.5, SD = 14.7). Results indicated an inverse relation between social support and diastolic BP (B = -.178, p = .005), and also an interaction with income (p = .046), such that higher social support related to lower diastolic BP in the lowest-income individuals (B = -1.05). The same direct (B = -.141, p = .025) and interacting (B = -1.42, p = .040) social support effects were present for systolic BP, however the omnibus model for systolic BP was not significant, F(6, 196) = 1.80, p = .09. The hypothesized buffering effect of social support on the adverse relation of income to BP was partially supported in at-risk African American adults. Future prevention efforts for reducing the impact of socioeconomic stress on BP may aim to increase perceptions of social support. PMID- 26156120 TI - For better or for worse: a longitudinal study on dyadic coping and quality of life among couples with a partner suffering from COPD. AB - In chronic obstructive pulmonary disease, impairments of dyadic coping are associated with reduced quality of life. However, existing studies have a cross sectional design. The present study explores changes in dyadic coping over time and its long-term effects on quality of life of both patients suffering from COPD and their partners. Dyadic coping, psychological distress, health-related quality of life, and exercise capacity were assessed in 63 patients suffering from COPD with their partners, at baseline and 3-year-follow-up. Correlation analyses and actor-partner interdependence models (APIMs) were conducted. Patients' delegated dyadic coping (taking over tasks) and common dyadic coping (mutual coping efforts when both partners are stressed) rated by the spouses decreased. Correlation analyses showed that patients' quality of life at follow-up was positively influenced by partners' stress communication (signaling stress). Partners' quality of life at follow-up was negatively influenced by patients' negative dyadic coping (reacting superficially, ambivalently or hostilely) and positively influenced by partners' delegated dyadic coping rated by patients (taking over tasks). APIMs mostly supported these results. It seems important that both partners communicate about stress and provide appropriate instrumental and emotional support to maintain quality of life. PMID- 26156121 TI - Do n-alkane biomarkers in soils/sediments reflect the delta2H isotopic composition of precipitation? A case study from Mt. Kilimanjaro and implications for paleoaltimetry and paleoclimate research. AB - During the last decade compound-specific deuterium ((2)H) analysis of plant leaf wax-derived n-alkanes has become a promising and popular tool in paleoclimate research. This is based on the widely accepted assumption that n-alkanes in soils and sediments generally reflect delta(2)H of precipitation (delta(2)H(prec)). Recently, several authors suggested that delta(2)H of n-alkanes (delta(2)H(n alkanes)) can also be used as a proxy in paleoaltimetry studies. Here, we present results from a delta(2)H transect study (~1500 to 4000 m above sea level [a.s.l.]) carried out on precipitation and soil samples taken from the humid southern slopes of Mt. Kilimanjaro. Contrary to earlier suggestions, a distinct altitude effect in delta(2)H(prec) is present above ~2000 m a.s.l., that is, delta(2)H(prec) values become more negative with increasing altitude. The compound-specific delta(2)H values of nC27 and nC29 do not confirm this altitudinal trend, but rather become more positive both in the O-layers (organic layers) and the Ah-horizons (mineral topsoils). Although our delta(2)H(n-alkane) results are in agreement with previously published results from the southern slopes of Mt. Kilimanjaro [Peterse F, van der Meer M, Schouten S, Jia G, Ossebaar J, Blokker J, Sinninghe Damste J. Assessment of soil n-alkane deltaD and branched tetraether membrane lipid distributions as tools for paleoelevation reconstruction. Biogeosciences. 2009;6:2799-2807], a re-interpretation is required given that the delta(2)H(n-alkane) results do not reflect the delta(2)H(prec) results. The theoretical framework for this re-interpretation is based on the evaporative isotopic enrichment of leaf water associated with the transpiration process. Modelling results show that relative humidity, decreasing considerably along the southern slopes of Mt. Kilimanjaro (from 78% in ~2000 m a.s.l. to 51% in 4000 m a.s.l.), strongly controls delta(2)H(leaf water). The modelled (2)H leaf water enrichment along the altitudinal transect matches well the measured (2)H leaf water enrichment as assessed by using the delta(2)H(prec) and delta(2)H(n-alkane) results and biosynthetic fractionation during n-alkane biosynthesis in leaves. Given that our results clearly demonstrate that n-alkanes in soils do not simply reflect delta(2)H(prec) but rather delta(2)H(leaf water), we conclude that care has to be taken not to over-interpret delta(2)H(n-alkane) records from soils and sediments when reconstructing delta(2)H of paleoprecipitation. Both in paleoaltimetry and in paleoclimate studies changes in relative humidity and consequently in delta(2)H(n-alkane) values can completely mask altitudinally or climatically controlled changes in delta(2)H(prec). PMID- 26156122 TI - Bendamustine in heavily pre-treated patients with relapsed or refractory multiple myeloma. AB - PURPOSE: Treatment options for patients with relapsed and refractory multiple myeloma have improved since the introduction of immune-modulating agents such as lenalidomide and thalidomide. However, almost all patients relapse and suffer from an increasing amount of adverse events due to multiple lines of therapy that eventually lead to a reduced quality of life. METHODS: In this bicentric retrospective analysis, 58 patients who had been treated with either bendamustine monotherapy (62 % of the patients) or combined steroid therapy were included. Further inclusion criteria were at least relapsed disease. Patients had previously been treated with a mean of four lines of therapy (range 1-10). They received a median of three cycles of treatment. Dosage varied from 60 to 300 mg/m(2) (median 120 mg/m(2)) and was administered intravenously on day 1 and 2 of a 28-day cycle. RESULTS: Observed toxicity was mild and most commonly led to hematological side effects such as thrombopenia and anemia. Response rates were as follows: no complete response, 20 % partial response, 39 % minimal response, 27 % stable disease and 14 % progressive disease. Median overall survival (OS) was 17 months. Median event-free survival was 7 months. Patients who had not received a concomitant steroid had a median OS of 17 months compared to 13 months median OS for patients who had received a concomitant steroid. CONCLUSION: Bendamustine monotherapy is an effective treatment option for heavily pre-treated myeloma patients due to its favorable response rate and mild toxicity. PMID- 26156124 TI - Whole Brain 1H-Spectroscopy: A Developing Technique for Advanced Analysis of Cerebral Metabolism. AB - OBJECTIVE: Accompanying the advance of neuroscientific research and modern therapeutic methods, efforts have been made to develop more practical and effective advanced magnetic resonance (MR) spectroscopic techniques. METHODS: We present a brief overview on (1)H-MRS techniques in neuroradiological diagnosis and several application examples of recently reported whole brain MR spectroscopic imaging technique (wbMRSI). RESULTS: Despite the benefits of using established (1)H-MRS techniques both single voxel MR spectroscopy (SVS) and chemical shift imaging (CSI) techniques suffer from limited spatial coverage. It is always necessary to define prior to the MRS examination which brain structure is physiologically or pathologically involved and thus should be targeted with (1)H-MRS. In contrast, the advanced wbMRSI allows estimating metabolite changes within a much larger brain region and at multiple brain structures simultaneously. CONCLUSIONS: As a developing technique for advanced analysis of cerebral metabolism a wide application of the wbMRSI in both clinical diagnostics and neuroscience could be expected. PMID- 26156125 TI - Photosystem II repair in marine diatoms with contrasting photophysiologies. AB - Skeletonema costatum and Phaeodactylum tricornutum are model marine diatoms with differing strategies for non-photochemical dissipation of excess excitation energy within photosystem II (PSII). We showed that S. costatum, with connectivity across the pigment bed serving PSII, and limited capacity for induction of sustained non-photochemical quenching (NPQ), maintained a large ratio of [PSII(Total)]/[PSII(Active)] to buffer against fluctuations in light intensity. In contrast, P. tricornutum, with a larger capacity to induce sustained NPQ, could maintain a lower [PSII(Total)]/[PSII(Active)]. Induction of NPQ was correlated with an active PSII repair cycle in both species, and inhibition of chloroplastic protein synthesis with lincomycin leads to run away over-excitation of remaining PSII(Active), particularly in S. costatum. We discuss these distinctions in relation to the differing capacities, induction and relaxation rates for NPQ, and as strain adaptations to the differential light regimes of their originating habitats. The present work further confirms the important role for the light-dependent fast regulation of photochemistry by NPQ interacting with PSII repair cycle capacity in the ecophysiology of both pennate and centric diatoms. PMID- 26156123 TI - Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates. AB - The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under long-term balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNA-binding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism. PMID- 26156127 TI - Bottom-up effects of a no-take zone on endangered penguin demographics. AB - Marine no-take zones can have positive impacts for target species and are increasingly important management tools. However, whether they indirectly benefit higher order predators remains unclear. The endangered African penguin (Spheniscus demersus) depends on commercially exploited forage fish. We examined how chick survival responded to an experimental 3-year fishery closure around Robben Island, South Africa, controlling for variation in prey biomass and fishery catches. Chick survival increased by 18% when the closure was initiated, which alone led to a predicted 27% higher population compared with continued fishing. However, the modelled population continued to decline, probably because of high adult mortality linked to poor prey availability over larger spatial scales. Our results illustrate that small no-take zones can have bottom-up benefits for highly mobile marine predators, but are only one component of holistic, ecosystem-based management regimes. PMID- 26156126 TI - Functional Roles of Aromatic Residues and Helices of Papiliocin in its Antimicrobial and Anti-inflammatory Activities. AB - A cecropin-like peptide, papiliocin, isolated from the swallowtail butterfly Papilio xuthus, possesses high selectivity against gram-negative bacteria. Since Trp(2) and Phe(5) are highly conserved residues in cecropin-like peptides, we investigated the role of Trp(2) and Phe(5) in antibacterial activity. Substitution of Trp(2) and Phe(5) in papiliocin with Ala (papiliocin-2A and papiliocin-5A) revealed that Trp(2) is a key residue in its antibacterial activities. In order to understand the structural requirements for papiliocin function and to design shorter, but more potent, peptide antibiotics, we designed papiliocin constructs, PapN (residues Arg(1)-Ala(22) from the N-terminal amphipathic helix). PapN exhibited significant broad-spectrum antibacterial activities without cytotoxicity. Bactericidal kinetics of peptides against E.coli showed that papiliocin completely and rapidly killed E.coli in less than 10 minutes at 2* MIC concentration, while papiliocin-2A and papiliocin-5A killed four times more slowly than papiliocin. The PapN series peptides permeabilized bacterial membranes less effectively than papiliocin, showing no antibacterial activities in an hour. The results imply that the Trp(2) and Phe(5) in the amphipathic N-terminal helix are important in the rapid permeabilization of the gram-negative bacterial membrane. The hydrophobic C-terminal residues permeabilize the hydrophobic bacterial cell membrane synergistically with these aromatic residues, providing selectivity against gram-negative bacteria. PMID- 26156128 TI - The costs of avian brood parasitism explain variation in egg rejection behaviour in hosts. AB - Many bird species can reject foreign eggs from their nests. This behaviour is thought to have evolved in response to brood parasites, birds that lay their eggs in the nest of other species. However, not all hosts of brood parasites evict parasitic eggs. In this study, we collate data from egg rejection experiments on 198 species, and perform comparative analyses to understand the conditions under which egg rejection evolves. We found evidence, we believe for the first time in a large-scale comparative analysis, that (i) non-current host species have rejection rates as high as current hosts, (ii) egg rejection is more likely to evolve when the parasite is relatively large compared with its host and (iii) egg rejection is more likely to evolve when the parasite chick evicts all the host eggs from the nest, such as in cuckoos. Our results suggest that the interactions between brood parasites and their hosts have driven the evolution of egg rejection and that variation in the costs inflicted by parasites is fundamental to explaining why only some host species evolve egg rejection. PMID- 26156129 TI - RAD sequencing and genomic simulations resolve hybrid origins within North American Canis. AB - Top predators are disappearing worldwide, significantly changing ecosystems that depend on top-down regulation. Conflict with humans remains the primary roadblock for large carnivore conservation, but for the eastern wolf (Canis lycaon), disagreement over its evolutionary origins presents a significant barrier to conservation in Canada and has impeded protection for grey wolves (Canis lupus) in the USA. Here, we use 127,235 single-nucleotide polymorphisms (SNPs) identified from restriction-site associated DNA sequencing (RAD-seq) of wolves and coyotes, in combination with genomic simulations, to test hypotheses of hybrid origins of Canis types in eastern North America. A principal components analysis revealed no evidence to support eastern wolves, or any other Canis type, as the product of grey wolf * western coyote hybridization. In contrast, simulations that included eastern wolves as a distinct taxon clarified the hybrid origins of Great Lakes-boreal wolves and eastern coyotes. Our results support the eastern wolf as a distinct genomic cluster in North America and help resolve hybrid origins of Great Lakes wolves and eastern coyotes. The data provide timely information that will shed new light on the debate over wolf conservation in eastern North America. PMID- 26156130 TI - The evolution and extinction of the ichthyosaurs from the perspective of quantitative ecospace modelling. AB - The role of niche specialization and narrowing in the evolution and extinction of the ichthyosaurs has been widely discussed in the literature. However, previous studies have concentrated on a qualitative discussion of these variables only. Here, we use the recently developed approach of quantitative ecospace modelling to provide a high-resolution quantitative examination of the changes in dietary and ecological niche experienced by the ichthyosaurs throughout their evolution in the Mesozoic. In particular, we demonstrate that despite recent discoveries increasing our understanding of taxonomic diversity among the ichthyosaurs in the Cretaceous, when viewed from the perspective of ecospace modelling, a clear trend of ecological contraction is visible as early as the Middle Jurassic. We suggest that this ecospace redundancy, if carried through to the Late Cretaceous, could have contributed to the extinction of the ichthyosaurs. Additionally, our results suggest a novel model to explain ecospace change, termed the 'migration model'. PMID- 26156131 TI - First evidence of neurons in the male copulatory organ of a spider (Arachnida, Araneae). AB - Spider males have evolved a remarkable way of transferring sperm by using a modified part of their pedipalps, the so-called palpal organ. The palpal organ is ontogenetically derived from tarsal claws; however, no nerves, sensory organs or muscles have been detected in the palpal bulb so far, suggesting that the spider male copulatory organ is numb and sensorily blind. Here, we document the presence of neurons and a nerve inside the male palpal organ of a spider for the first time. Several neurons that are located in the embolus are attached to the surrounding cuticle where stresses and strains lead to a deformation (stretching) of the palpal cuticle on a local scale, suggesting a putative proprioreceptive function. Consequently, the male copulatory organ of this species is not just a numb structure but likely able to directly perceive sensory input during sperm transfer. In addition, we identified two glands in the palpal organ, one of which is located in the embolus (embolus gland). The embolus gland appears to be directly innervated, which could allow for rapid modulation of secretory activity. Thus, we hypothesize that the transferred seminal fluid can be modulated to influence female processes. PMID- 26156132 TI - The influence of preceding dive cycles on the foraging decisions of Antarctic fur seals. AB - The foraging strategy of many animals is thought to be determined by their past experiences. However, few empirical studies have investigated whether this is true in diving animals. We recorded three-dimensional movements and mouth-opening events from three Antarctic fur seals during their foraging trips to examine how they adapt their behaviour based on past experience--continuing to search for prey in the same area or moving to search in a different place. Each dive cycle was divided into a transit phase and a feeding phase. The linear horizontal distance travelled after feeding phases in each dive was affected by the mouth opening rate during the previous 244 s, which typically covered two to three dive cycles. The linear distance travelled tended to be shorter when the mouth-opening rate in the previous 244 s was higher, i.e. seals tended to stay in the same areas with high prey-encounter rates. These results indicate that Antarctic fur seals follow decision-making strategies based on the past foraging experience over time periods longer than the immediately preceding dive. PMID- 26156133 TI - Efficient introgression of allelic variants by embryo-mediated editing of the bovine genome. AB - The recent development of designer nucleases allows for the efficient and precise introduction of genetic change into livestock genomes. Most studies so far have focused on the introduction of random mutations in cultured cells and the use of nuclear transfer to generate animals with edited genotypes. To circumvent the intrinsic uncertainties of random mutations and the inefficiencies of nuclear transfer we directed our efforts to the introduction of specific genetic changes by homology-driven repair directly in in vitro produced embryos. Initially, we injected zinc finger nuclease (ZFN)-encoding mRNA or DNA into bovine zygotes to verify cleavage activity at their target site within the gene for beta lactoglobulin (LGB) and detected ZFN-induced random mutations in 30% to 80% of embryos. Next, to precisely change the LGB sequence, we co-injected ZFNs or transcription activator-like effector nucleases (TALENs) with DNA oligonucleotides (ODNs). Analysis of co-injected embryos showed targeted changes in up to 33% (ZFNs) and 46% (TALENs) of blastocysts. Deep sequence analysis of selected embryos revealed contributions of the targeted LGB allele can reach 100% which implies that genome editing by zygote injections can facilitate the one step generation of non-mosaic livestock animals with pre-designed biallelic modifications. PMID- 26156134 TI - Real-Time Visualization of Platelet Interaction With Micro Structured Surfaces. AB - Improving the hemocompatibility of artificial implants by micro structuring their surfaces has shown promising results, but the mechanisms which lead to this improvement are not yet understood. Therefore, we built a test setup for real time visualization of platelet interaction with a plain and two micro structured surfaces. The micro structures, defined by the distance of the plain surface area between the structures, were chosen to be 3 and 30 MUm, representing a positive and a negative effect on the hemocompatibility. The main part of the test setup was a flow chamber containing films of low density polyethylene (LDPE) with the differently structured surfaces. For different wall shear stresses, no considerable differences were observed in the platelet-surface interaction for all surface types. Whereas, major differences in flow behavior were observed when comparing the surfaces to each other. The platelets "rolled" along the smooth surface, being in constant contact with the surface material. Although the platelets "rolled" over the surface with small structures as well, they were only in contact with the tips of the structure and therefore had less surface contact with the foreign material. The increased distance and height of the structures of the last surface led to a trapping of platelets between the structures. This resulted in a longer contact time with the foreign material as well as a larger contact area, which both increase the risk of platelet activation, adhesion, and finally clotting. Our results showed the mechanisms which lead to these effects and thus revealed why micro structuring of surfaces impacts the hemocompatibility. Furthermore, we established a test setup which can be used for future investigations on the platelet-structure interactions. PMID- 26156135 TI - Potential sources of airborne Alternaria spp. spores in South-west Spain. AB - Fungi belonging to the genus of Alternaria are recognised as being significant plant pathogens, and Alternaria allergens are one of the most important causes of respiratory allergic diseases in Europe. This study aims to provide a detailed and original analysis of Alternaria transport dynamics in Badajoz, SW Spain. This was achieved by examining daily mean and hourly observations of airborne Alternaria spores recorded during days with high airborne concentrations of Alternaria spores (>100 s m(-3)) from 2009 to 2011, as well as four inventory maps of major Alternaria habitats, the overall synoptic weather situation and analysis of air mass transport using Hybrid Single Particle Lagrangian Integrated Trajectory model and geographic information systems. Land use calculated within a radius of 100 km from Badajoz shows that crops and grasslands are potentially the most important local sources of airborne Alternaria spores recorded at the site. The results of back trajectory analysis show that, during the examined four episodes, the two main directions where Alternaria source areas were located were: (1) SW-W; and (2) NW-NE. Regional scale and long distance transport could therefore supplement the airborne catch recorded at Badajoz with Alternaria conidia originating from sources such as crops and orchards situated in other parts of the Iberian Peninsula. PMID- 26156136 TI - Chemical and microbiological characterization of an aged PCB-contaminated soil. AB - This study was aimed at complex characterization of three soil samples (bulk soil, topsoil and rhizosphere soil) from a site historically contaminated with polychlorinated biphenyls (PCB). The bulk soil was the most highly contaminated, with a PCB concentration of 705.95 mg kg(-1), while the rhizosphere soil was the least contaminated (169.36 mg kg(-1)). PCB degradation intermediates, namely chlorobenzoic acids (CBAs), were detected in all the soil samples, suggesting the occurrence of microbial transformation processes over time. The higher content of organic carbon in the topsoil and rhizosphere soil than in the bulk soil could be linked to the reduced bioaccessibility (bioavailability) of these chlorinated pollutants. However, different proportions of the PCB congener contents and different bioaccessibility of the PCB homologues indicate microbial biotransformation of the compounds. The higher content of organic carbon probably also promoted the growth of microorganisms, as revealed by phospholipid fatty acid (PFLA) quantification. Tag-encoded pyrosequencing analysis showed that the bacterial community structure was significantly similar among the three soils and was predominated by Proteobacteria (44-48%) in all cases. Moreover, analysis at lower taxonomic levels pointed to the presence of genera (Sphingomonas, Bulkholderia, Arthrobacter, Bacillus) including members with reported PCB removal abilities. The fungal community was mostly represented by Basidiomycota and Ascomycota, which accounted for >80% of all the sequences detected in the three soils. Fungal taxa with biodegradation potential (Paxillus, Cryptococcus, Phoma, Mortierella) were also found. These results highlight the potential of the indigenous consortia present at the site as a starting point for PCB bioremediation processes. PMID- 26156137 TI - The distribution of Polychlorinated Biphenyls (PCBs) in the River Thames Catchment under the scenarios of climate change. AB - Measurements have shown low levels of PCBs in water but relatively high concentrations in the resident fish of the River Thames (UK). To better understand the distribution and behaviour of PCBs in the Thames river basin and their potential risks, a level III fugacity model was applied to selected PCB congeners (PCB 52, PCB 118 and PCB 153). The modelling results indicated that fish and sediments represent environmental compartments with the highest PCB concentrations; but the greatest mass of PCBs (over 70%) is likely to remain in the soil. As emissions decline, soil could then act as a significant secondary source of PCBs with the river bed-sediment functioning as a long-term reservoir of PCBs. The predicted changes in temperature and rainfall forecast in the UK Climate Projections 2009 (UKCP09) over the next 80 years had only a modest influence on PCB fate in the model. The most significant result was a tendency for climate change to enhance the evaporation of PCBs from soil to air in the Thames catchment. PMID- 26156138 TI - Plasmakinetic resection technology for the treatment of benign prostatic hyperplasia: evidence from a systematic review and meta-analysis. AB - The aim of this study was to compare plasmakinetic resection of the prostate (PKRP) with transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) in terms of efficacy and safety. Published RCTs were searched from PubMed, Embase, Science Citation Index, and Cochrane Library up to April 10, 2014. After methodological quality assessment and data extraction, meta-analysis was performed using the STATA 12.0 software. 18 reports of 16 RCTs were included in this analysis. Meta-analyses showed that PKRP significantly improved Qmax at 12 months, but no significant difference was found for other efficacy outcomes. In terms of safety, treatment of PKRP was associated with reduced drop in serum sodium, lower TUR syndrome, reduced need of blood transfusion, clot retention, and shorter catheterization time and hospital stay; in contrast, there were no significant differences in the analysis of operative time, postoperative fever, and long-term postoperative complications. In summary, current evidence suggests that, although PKRP and TURP are both effective for BPH, PKRP is associated with additional potential benefits in efficacy and more favorable safety profile. It may be possible that PKRP may replace the TURP in the future and become a new standard surgical procedure. PMID- 26156139 TI - New routes to control nanoparticle synthesis: general discussion. PMID- 26156141 TI - Frequent and long-term follow-up of health-related quality of life following allogeneic haematopoietic stem cell transplantation. AB - Health-related quality of life (HRQL) was evaluated in 94 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) after myeloablative (MAC, n = 18) or reduced intensity conditioning (RIC, n = 76). HRQL was assessed with the EORTC QLQ C-30 during the inpatient period as well as during the following 3 years, i.e., at baseline and 12 times thereafter. Functional status and global quality of life decreased from baseline to weeks 2 and 3, especially role and social functions. Symptoms increased significantly during the first 3 weeks, particularly appetite loss, nausea and vomiting, diarrhoea and fatigue. It took at least 1 year for HRQL to return to the baseline level. The only function that improved significantly 3 years after HSCT was role function. Patients treated with MAC experienced significantly worse HRQL at baseline than patients treated with RIC, as well as more pain, sleep disturbance and appetite loss in weeks 3 and 4. Patients with extensive chronic graft-versus-host disease experienced reduced HRQL. These results provide a clinically useful overview of patients' HRQL during and after HSCT and indicate when they require increased support. The results demonstrate the importance of close follow-ups during the first year after HSCT to improve preventive or supportive interventions. PMID- 26156140 TI - Cell periphery-related proteins as major genomic targets behind the adaptive evolution of an industrial Saccharomyces cerevisiae strain to combined heat and hydrolysate stress. AB - BACKGROUND: Laboratory evolution is an important tool for developing robust yeast strains for bioethanol production since the biological basis behind combined tolerance requires complex alterations whose proper regulation is difficult to achieve by rational metabolic engineering. Previously, we reported on the evolved industrial Saccharomyces cerevisiae strain ISO12 that had acquired improved tolerance to grow and ferment in the presence of lignocellulose-derived inhibitors at high temperature (39 degrees C). In the current study, we used comparative genomics to uncover the extent of the genomic alterations that occurred during the evolution process and investigated possible associations between the mutations and the phenotypic traits in ISO12. RESULTS: Through whole genome sequencing and variant calling we identified a high number of strain unique SNPs and INDELs in both ISO12 and the parental strain Ethanol Red. The variants were predicted to have 760 non-synonymous effects in both strains combined and were significantly enriched in Gene Ontology terms related to cell periphery, membranes and cell wall. Eleven genes, including MTL1, FLO9/FLO11, and CYC3 were found to be under positive selection in ISO12. Additionally, the FLO genes exhibited changes in copy number, and the alterations to this gene family were correlated with experimental results of multicellularity and invasive growth in the adapted strain. An independent lipidomic analysis revealed further differences between the strains in the content of nine lipid species. Finally, ISO12 displayed improved viability in undiluted spruce hydrolysate that was unrelated to reduction of inhibitors and changes in cell wall integrity, as shown by HPLC and lyticase assays. CONCLUSIONS: Together, the results of the sequence comparison and the physiological characterisations indicate that cell-periphery proteins (e.g. extracellular sensors such as MTL1) and peripheral lipids/membranes are important evolutionary targets in the process of adaptation to the combined stresses. The capacity of ISO12 to develop complex colony formation also revealed multicellularity as a possible evolutionary strategy to improve competitiveness and tolerance to environmental stresses (also reflected by the FLO genes). Although a panel of altered genes with high relevance to the novel phenotype was detected, this study also demonstrates that the observed long term molecular effects of thermal and inhibitor stress have polygenetic basis. PMID- 26156142 TI - Machine learning approach for pooled DNA sample calibration. AB - BACKGROUND: Despite ongoing reduction in genotyping costs, genomic studies involving large numbers of species with low economic value (such as Black Tiger prawns) remain cost prohibitive. In this scenario DNA pooling is an attractive option to reduce genotyping costs. However, genotyping of pooled samples comprising DNA from many individuals is challenging due to the presence of errors that exceed the allele frequency quantisation size and therefore cannot be simply corrected by clustering techniques. The solution to the calibration problem is a correction to the allele frequency to mitigate errors incurred in the measurement process. We highlight the limitations of the existing calibration solutions such as the fact they impose assumptions on the variation between allele frequencies 0, 0.5, and 1.0, and address a limited set of error types. We propose a novel machine learning method to address the limitations identified. RESULTS: The approach is tested on SNPs genotyped with the Sequenom iPLEX platform and compared to existing state of the art calibration methods. The new method is capable of reducing the mean square error in allele frequency to half that achievable with existing approaches. Furthermore for the first time we demonstrate the importance of carefully considering the choice of training data when using calibration approaches built from pooled data. CONCLUSION: This paper demonstrates that improvements in pooled allele frequency estimates result if the genotyping platform is characterised at allele frequencies other than the homozygous and heterozygous cases. Techniques capable of incorporating such information are described along with aspects of implementation. PMID- 26156143 TI - Difficult access in the anaesthetic room leads to a difficult diagnosis. PMID- 26156144 TI - Isolation of strong constitutive promoters from Lactococcus lactis subsp. lactis N8. AB - The synthesis of heterologous proteins in Lactococcus lactis is strongly influenced by the promoter selected for the expression. The nisin A promoter is commonly used for induced expression of proteins in L. lactis, whereas few constitutive promoters (P45 and the weaker P32) have been used for protein expression studies. In this study, eight different putative strong constitutive promoters were identified through transcriptional analysis of L. lactis N8 and were investigated for their capability to drive nisZ gene expression with promoters P45 and P32 as control. Four strong promoters (P8, P5, P3 and P2) were identified as having a transcriptional activity that was higher than that of P45 through RT-qPCR and agar-diffusion experiments. In addition, these four promoters were fused to the erythromycin resistant gene (ermC) with promoter P45 as control and inserted into the backbone of the pNZ8048 vector. The transcriptional efficiencies of promoters P8, P5, P2 and P3 were all higher than promoter P45 based on the obtained MIC50 values and they all showed different activity levels. In conclusion, four strong constitutive promoters with a wide range of promoter activities were identified and are suitable for protein production in L. lactis. PMID- 26156145 TI - Knowledge, Attitude, and Practice Related to Diabetes Mellitus Among Diabetics and Nondiabetics Visiting Homeopathic Hospitals in West Bengal, India. AB - High prevalence of undiagnosed cases of diabetes mellitus and poor knowledge, awareness, and practice has increased premature death, costly complications, and financial burden. A cross-sectional survey was conducted in November 2014 on 273 diabetics and 355 nondiabetics in 3 government homeopathic hospitals in West Bengal, India. A self-administered questionnaire assessing knowledge, awareness, and practice related to diabetes was used. A total of 17.5% to 29.3% of the participants were aware of the normal blood sugar level. Lack of insulin, frequent urination, hypertension, and poor wound healing were identified most frequently as the cause, symptom, association, and complications. A total of 35.5% to 46.5% said that diabetes was preventable; 14.1% to 31.9% knew that diabetes was controllable rather than curable. Consumption of planned diet, avoiding sugar, and testing blood sugar were the most frequently identified components of healthy lifestyle, diabetic diet, and diagnostic domain. Diabetics had higher knowledge and awareness than nondiabetics (P < .0001); still the latter need to be made aware and knowledgeable to curtail the ever-increasing burden of diabetes. PMID- 26156147 TI - Cardiovascular Update: Risk, Guidelines, and Recommendations. AB - This article provides an update of the current status of cardiovascular disease (CVD) in the United States, including a brief review of the underlying pathophysiology and epidemiology. This article presents a discussion of the latest American Heart Association guidelines that introduce the concept of promoting ideal cardiovascular health, defined by seven identified metrics. Specific CVD risk factors and utilization of the 10-year CVD event prediction calculator are discussed. In addition, current management recommendations of health-related conditions that increase risk for CVD, such as hypertension and hypercholesterolemia, are provided. Finally, a discussion of detailed evidence based lifestyle recommendations to promote cardiovascular health and reduce CVD risks concludes the update. PMID- 26156146 TI - The Effects of Caffeine Use on Driving Safety Among Truck Drivers Who Are Habitual Caffeine Users. AB - The purpose of this study was to describe caffeine use among a group of habitual caffeine users, truck drivers, and to explore the associations between caffeine use and critical safety events by age in the naturalistic work setting. A secondary analysis of existing data from the Naturalistic Truck Driving Study was conducted. Analyses focused on the association between sleep and caffeine consumption by duty status, comparisons of sleep and caffeine use by age, and the associations between caffeine use and safety-critical events (SCEs). Findings indicated differences in caffeine use by duty status. However, no difference in sleep time by duty status, or between sleep time and caffeine use was found regardless of when the caffeine was consumed during the 5 hours prior to sleep. Sleep time did not vary significantly by age, although increasing age was associated with decreased caffeine use. Overall, a 6% reduction in the rate of SCEs per eight ounces of caffeinated beverage consumed was found. This study makes a unique scientific contribution because it uses real-time observations of truckers in the naturalistic work setting. It also does not involve caffeine withdrawal but rather an investigation of the effects of the naturalistic consumption of caffeine on sleep and driving performance. Findings suggest that caffeine use among habitual users offers a protective effect for safety-critical driving events. Occupational health nurses may use this information to counsel workers in the use of caffeine to enhance driving safety. PMID- 26156148 TI - First-in-Human Case of Transfemoral CardiAQ Mitral Valve Implantation. PMID- 26156149 TI - Effect of Pulmonary Hypertension Hemodynamic Presentation on Clinical Outcomes in Patients With Severe Symptomatic Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation: Insights From the New Proposed Pulmonary Hypertension Classification. AB - BACKGROUND: Pulmonary hypertension (PH) frequently coexists with severe aortic stenosis, and PH severity has been shown to predict outcomes after transcatheter aortic valve implantation (TAVI). The effect of PH hemodynamic presentation on clinical outcomes after TAVI is unknown. METHODS AND RESULTS: Of 606 consecutive patients undergoing TAVI, 433 (71.4%) patients with severe aortic stenosis and a preprocedural right heart catheterization were assessed. Patients were dichotomized according to whether PH was present (mean pulmonary artery pressure, >=25 mm Hg; n=325) or not (n=108). Patients with PH were further dichotomized by left ventricular end-diastolic pressure into postcapillary (left ventricular end diastolic pressure, >15 mm Hg; n=269) and precapillary groups (left ventricular end-diastolic pressure, <=15 mm Hg; n=56). Finally, patients with postcapillary PH were divided into isolated (n=220) and combined (n=49) subgroups according to whether the diastolic pressure difference (diastolic pulmonary artery pressure left ventricular end-diastolic pressure) was normal (<7 mm Hg) or elevated (>=7 mm Hg). Primary end point was mortality at 1 year. PH was present in 325 of 433 (75%) patients and was predominantly postcapillary (n=269/325; 82%). Compared with baseline, systolic pulmonary artery pressure immediately improved after TAVI in patients with postcapillary combined (57.8+/-14.1 versus 50.4+/-17.3 mm Hg; P=0.015) but not in those with precapillary (49.0+/-12.6 versus 51.6+/-14.3; P=0.36). When compared with no PH, a higher 1-year mortality rate was observed in both precapillary (hazard ratio, 2.30; 95% confidence interval, 1.02-5.22; P=0.046) and combined (hazard ratio, 3.15; 95% confidence interval, 1.43-6.93; P=0.004) but not isolated PH patients (P=0.11). After adjustment, combined PH remained a strong predictor of 1-year mortality after TAVI (hazard ratio, 3.28; P=0.005). CONCLUSIONS: Invasive stratification of PH according to hemodynamic presentation predicts acute response to treatment and 1-year mortality after TAVI. PMID- 26156150 TI - Multimodality Intra-Arterial Imaging Assessment of the Vascular Trauma Induced by Balloon-Based and Nonballoon-Based Renal Denervation Systems. AB - BACKGROUND: Renal denervation is a new treatment considered for several possible indications. As new systems are introduced, the incidence of acute renal artery wall injury with relation to the denervation method is unknown. We investigated the acute repercussion of renal denervation on the renal arteries of patients treated with balloon-based and nonballoon-based denervation systems by quantitative angiography, intravascular ultrasound, and optical coherence tomography (OCT). METHODS AND RESULTS: Twenty-five patients (50 renal arteries) underwent bilateral renal denervation with 5 different systems, 3 of which balloon-based (Paradise [n=5], Oneshot [n=6], and Vessix V2 [n=5)]) and 2 nonballoon-based (Symplicity [n=6] and EnligHTN [n=3]). Analysis included quantitative angiography and morphometric intravascular ultrasound measurements pre and post procedure and assessment of vascular trauma (dissection, edema, or thrombus) by OCT after denervation. A significant reduction in lumen size by quantitative angiography and intravascular ultrasound was observed in nonballoon denervation but not in balloon denervation. By postdenervation OCT, dissection was seen in 14 arteries (32.6%). The percentage of frames with dissection was higher in balloon-based denervation catheters. Thrombus and edema were detected in 35 (81.4%) and 32 (74.4%) arteries, respectively. In arteries treated with balloon-based denervation that had dissection by OCT, the balloon/artery ratio was higher (1.24 [1.17-1.32] versus 1.10 [1.04-1.18]; P<0.01). CONCLUSIONS: A varying extent of vascular injury was observed after renal denervation in all systems; however, different patterns were identified in balloon-based and in nonballoon-based denervation systems. In balloon denervation, the presence of dissections by OCT was associated with a higher balloon/artery ratio. PMID- 26156151 TI - Clinical Impact of Intravascular Ultrasound-Guided Chronic Total Occlusion Intervention With Zotarolimus-Eluting Versus Biolimus-Eluting Stent Implantation: Randomized Study. AB - BACKGROUND: There have been no randomized studies comparing intravascular ultrasound (IVUS)-guided versus conventional angiography-guided chronic total occlusion (CTO) intervention using new-generation drug-eluting stent Therefore, we conducted a prospective, randomized, multicenter trial designed to test the hypothesis that IVUS-guided CTO intervention is superior to angiography-guided intervention. METHODS AND RESULTS: After successful guidewire crossing, 402 patients with CTOs were randomized to the IVUS-guided group (n=201) or the angiography-guided group (n=201) and secondarily randomized to Resolute zotarolimus-eluting stents or Nobori biolimus-eluting stents. The primary and secondary end points were cardiac death and a major adverse cardiac event defined as the composite of cardiac death, myocardial infarction, or target-vessel revascularization, respectively. After 12-month follow-up, the rate of cardiac death was not significantly different between the IVUS-guided group (0%) and the angiography-guided group (1.0%; P by log-rank test=0.16). However, major adverse cardiac event rates were significantly lower in the IVUS-guided group than that in the angiography-guided group (2.6% versus 7.1%; P=0.035; hazard ratio, 0.35; 95% confidence interval, 0.13-0.97). Occurrence of the composite of cardiac death or myocardial infarction was significantly lower in the IVUS-guided group (0%) than in the angiography-guided group (2.0%; P=0.045). The rates of target-vessel revascularization were not significantly different between the 2 groups. In the comparison between Resolute zotarolimus-eluting stent and Nobori biolimus-eluting stent, major adverse cardiac event rates were not significantly different (4.0% versus 5.7%; P=0.45). CONCLUSIONS: Although IVUS-guided CTO intervention did not significantly reduce cardiac mortality, this randomized study demonstrated that IVUS-guided CTO intervention might improve 12-month major adverse cardiac event rate after new-generation drug-eluting stent implantation when compared with conventional angiography-guided CTO intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01563952. PMID- 26156152 TI - Everolimus Eluting Stents Versus Coronary Artery Bypass Graft Surgery for Patients With Diabetes Mellitus and Multivessel Disease. AB - BACKGROUND: In patients with diabetes mellitus and multivessel disease, coronary artery bypass graft surgery and percutaneous coronary intervention are treatment options. However, there is paucity of data comparing coronary artery bypass graft surgery against newer generation stents. METHODS AND RESULTS: Patients included in the New York State registries who had diabetes mellitus and underwent isolated coronary artery bypass graft surgery or percutaneous coronary intervention with everolimus eluting stent (EES) for multivessel disease were included. Propensity score matching was used to assemble a cohort with similar baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes were myocardial infarction (MI), stroke, and repeat revascularization. Short-term (within 30 days) and long-term outcomes were evaluated. Among 16,089 patients with diabetes mellitus and multivessel disease, 8096 patients with similar propensity scores were included. At short-term, EES was associated with a lower risk of death (hazard ratio [HR] =0.58; 95% confidence interval [CI], 0.34-0.98; P=0.04) and stroke (HR=0.14; 95% CI, 0.06-0.30; P<0.0001) but higher risk of MI (HR=2.44; 95% CI, 1.13-5.31; P=0.02). At long-term, EES was associated with a similar risk of death (425 [10.50%] versus 414 [10.23%] events; HR=1.12; 95% CI, 0.96-1.30; P=0.16), a lower risk of stroke (118 [2.92%] versus 157 [3.88%] events; HR=0.76; 95% CI, 0.58-0.99; P=0.04) but a higher risk of MI (260 [6.42%] versus 166 [4.10%] events; HR=1.64; 95% CI, 1.32-2.04; P<0.0001) and repeat revascularization (889 [21.96%] versus 421 [10.40%] events; HR=2.42; 95% CI, 2.12 2.76; P<0.0001). The higher risk of MI was not seen in the subgroup of EES patients who underwent complete revascularization (HR=1.37; 95% CI, 0.76-2.47; P=0.30). CONCLUSIONS: In patients with diabetes mellitus and multivessel disease, EES was associated with lower upfront risk of death and stroke when compared with coronary artery bypass graft surgery. However, at long-term, EES was associated with similar risk of death, a higher risk of MI (in those with incomplete revascularization), and repeat revascularization but a lower risk of stroke. PMID- 26156153 TI - Letter by Saito Regarding Article, "Collateral Donor Artery Physiology and the Influence of a Chronic Total Occlusion on Fractional Flow Reserve". PMID- 26156154 TI - Response to Letter Regarding Article, "Collateral Donor Artery Physiology and the Influence of a Chronic Total Occlusion on Fractional Flow Reserve". PMID- 26156155 TI - Patellectomy for osteoarthritis: a new tension preserving surgical technique to reconstruct the extensor mechanism with retrospective review of long-term follow up. AB - BACKGROUND: The management of severe patellofemoral arthritis in young patients remains a significant problem. For many, patellofemoral replacement is not a desirable option. Current surgical techniques for patellectomy disrupt the extensor lever arm causing weakness. We describe a new technique that maintains the extensor mechanism tension and a case series showing good results for patella only arthritis at a mean follow-up of 11 years. METHODS: Eight patellectomies were performed using a new surgical technique in patients with a mean age of 38 years, and an average follow-up of 11 years (range 8-16 years). Patients were followed up using a pain visual analogue scale, Lysholm knee score and patient reported outcome measures. RESULTS: All patients experienced pain relief following surgery. Those with patella-only arthritis had better outcomes than patients who had patella and trochlea disease. All patients had either full or near full extension. Lysholm scores were better in patients who had disease confined to the patella. CONCLUSION: We believe patellectomy with this tension preserving technique has a role for the management of anterior knee pain secondary to severe patella-only arthritis in young patients where arthroplasty is not desirable. PMID- 26156156 TI - Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial. AB - BACKGROUND: In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30% of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. METHODS/DESIGN: PRODIGE 22- ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and completeness of the surgery, initial radiological staging and radiological response to neoadjuvant chemotherapy, and the correlation between histopathological and radiological response. Taking into account a 50% prevalence of CC without RAS mutation, accrual of 165 patients is needed for this Phase II trial. TRIAL REGISTRATION: NCT01675999 (ClinicalTrials.gov). PMID- 26156159 TI - Singlet-triplet annihilation in single LHCII complexes. AB - In light harvesting complex II (LHCII) of higher plants and green algae, carotenoids (Cars) have an important function to quench chlorophyll (Chl) triplet states and therefore avoid the production of harmful singlet oxygen. The resulting Car triplet states lead to a non-linear self-quenching mechanism called singlet-triplet (S-T) annihilation that strongly depends on the excitation density. In this work we investigated the fluorescence decay kinetics of single immobilized LHCIIs at room temperature and found a two-exponential decay with a slow (3.5 ns) and a fast (35 ps) component. The relative amplitude fraction of the fast component increases with increasing excitation intensity, and the resulting decrease in the fluorescence quantum yield suggests annihilation effects. Modulation of the excitation pattern by means of an acousto-optic modulator (AOM) furthermore allowed us to resolve the time-dependent accumulation and decay rate (~7 MUs) of the quenching species. Inspired by singlet-singlet (S S) annihilation studies, we developed a stochastic model and then successfully applied it to describe and explain all the experimentally observed steady-state and time-dependent kinetics. That allowed us to distinctively identify the quenching mechanism as S-T annihilation. Quantitative fitting resulted in a conclusive set of parameters validating our interpretation of the experimental results. The obtained stochastic model can be generalized to describe S-T annihilation in small molecular aggregates where the equilibration time of excitations is much faster than the annihilation-free singlet excited state lifetime. PMID- 26156158 TI - Vaccine coverage and determinants of incomplete vaccination in children aged 12 23 months in Dschang, West Region, Cameroon: a cross-sectional survey during a polio outbreak. AB - BACKGROUND: Inadequate immunization coverage with increased risk of vaccine preventable diseases outbreaks remains a problem in Africa. Moreover, different factors contribute to incomplete vaccination status. This study was performed in Dschang (West Region, Cameroon), during the polio outbreak occurred in October 2013, in order to estimate the immunization coverage among children aged 12-23 months, to identify determinants for incomplete vaccination status and to assess the risk of poliovirus spread in the study population. METHODS: A cross-sectional household survey was conducted in November-December 2013, using the WHO two-stage sampling design. An interviewer-administered questionnaire was used to obtain information from consenting parents of children aged 12-23 months. Vaccination coverage was assessed by vaccination card and parents' recall. Chi-square test and multilevel logistic regression model were used to identify the determinants of incomplete immunization status. Statistical significance was set at p < 0.05. RESULTS: Overall, 3248 households were visited and 502 children were enrolled. Complete immunization coverage was 85.9% and 84.5%, according to card plus parents' recall and card only, respectively. All children had received at least one routine vaccination, the OPV-3 (Oral Polio Vaccine) coverage was >90%, and 73.4% children completed the recommended vaccinations before 1-year of age. In the final multilevel logistic regression model, factors significantly associated with incomplete immunization status were: retention of immunization card (AOR: 7.89; 95% CI: 1.08-57.37), lower mothers' utilization of antenatal care (ANC) services (AOR:1.25; 95% CI: 1.07-63.75), being the >= 3(rd) born child in the family (AOR: 425.4; 95% CI: 9.6-18,808), younger mothers' age (AOR: 49.55; 95% CI: 1.59-1544), parents' negative attitude towards immunization (AOR: 20.2; 95% CI: 1.46-278.9), and poorer parents' exposure to information on vaccination (AOR: 28.07; 95 % CI: 2.26-348.1). Longer distance from the vaccination centers was marginally significant (p = 0.05). CONCLUSION: Vaccination coverage was high; however, 1 out of 7 children was partially vaccinated, and 1 out of 4 did not complete timely the recommended vaccinations. In order to improve the immunization coverage, it is necessary to strengthen ANC services, and to improve parents' information and attitude towards immunization, targeting younger parents and families living far away from vaccination centers, using appropriate communication strategies. Finally, the estimated OPV-3 coverage is reassuring in relation to the ongoing polio outbreak. PMID- 26156157 TI - Engineering New Approaches to Cancer Vaccines. AB - Recently, a number of promising approaches have been developed using synthetic chemistry, materials science, and bioengineering-based strategies to address challenges in the design of more effective cancer vaccines. At the stage of initial priming, potency can be improved by maximizing vaccine delivery to lymph nodes. Because lymphatic uptake from peripheral tissues is strongly size dependent, antigens and adjuvants packaged into optimally sized nanoparticles access the lymph node with much greater efficiency than unformulated vaccines. Once primed, T cells must home to the tumor site. Because T cells acquire the necessary surface receptors in the local lymph node draining the tissue of interest, vaccines must be engineered that reach organs, such as the lung and gut, which are common sites of tumor lesions but inaccessible by traditional vaccination routes. Particulate vaccine carriers can improve antigen exposure in these organs, resulting in greater lymphocyte priming. Immunomodulatory agents can also be injected directly into the tumor site to stimulate a systemic response capable of clearing even distal lesions; materials have been designed that entrap or slowly release immunomodulators at the tumor site, reducing systemic exposure and improving therapeutic efficacy. Finally, lessons learned from the design of biomaterial-based scaffolds in regenerative medicine have led to the development of implantable vaccines that recruit and activate antigen presenting cells to drive antitumor immunity. Overall, these engineering strategies represent an expanding toolkit to create safe and effective cancer vaccines. PMID- 26156160 TI - Isolation, purification and in vitro differentiation of cytotrophoblast cells from human term placenta. AB - BACKGROUND: The syncytialization of cytotrophoblast cells to syncytiotrophoblast is central to human placental transport and hormone production. Many techniques for in vitro study of this process have been proposed and new investigators to the field may find the literature in the field daunting. Here, we present a straightforward and reliable method to establish this important model using modern but readily available tools and reagents. METHODS: Villous cytotrophoblast cells are obtained from term placenta using mild enzymatic degradation, Percoll gradient centrifugation, negative magnetic cell sorting using an antibody against classical major histocompatibility complex molecules and in vitro culture on a matrix-coated growth surface. RESULTS: The purity of isolated cytotrophoblast cells exceeds 98 % as assessed by cytokeratin-7 expression using flow cytometry. Contamination by mesenchymal cells, extravillous trophoblast cells, leukocytes, Hofbauer and endothelial cells is minimized (less than 2 % when analyzed for vimentin, HLA-G, CD45, CD163 and CD31 using flow cytometry). Isolated cytotrophoblast cells began to aggregate into monolayers of mononucleated cells within about 12 h of plating. By 72 h in culture, most cytotrophoblast cells have differentiated into syncytiotrophoblast as demonstrated by a loss of intercellular E-cadherin expression upon fusion into multinucleated syncytia. After 72 h in culture, nearly every cultured cell expresses syncytiotrophoblast markers, including cytokeratin-7, human chorionic gonadotropin-beta (beta-hCG) and the fusion-related proteins glial cell missing-1 (GCM-1) and syncytin. CONCLUSIONS: We present an efficient and reliable method for isolating of cytotrophoblast cells with high purity and complete differentiation into syncytiotrophoblast in vitro. PMID- 26156161 TI - Performance Evaluation of an Improved GC-MS Method to Quantify Methylmercury in Fish. AB - Here, we set out to improve our previously developed methylmercury analytical method, involving phenyl derivatization and gas chromatography-mass spectrometry (GC-MS). In the improved method, phenylation of methylmercury with sodium tetraphenylborate was carried out in a toluene/water two-phase system, instead of in water alone. The modification enabled derivatization at optimum pH, and the formation of by-products was dramatically reduced. In addition, adsorption of methyl phenyl mercury in the GC system was suppressed by co-injection of PEG200, enabling continuous analysis without loss of sensitivity. The performance of the improved analytical method was independently evaluated by three analysts using certified reference materials and methylmercury-spiked fresh fish samples. The present analytical method was validated as suitable for determination of compliance with the provisional regulation value for methylmercury in fish, set in the Food Sanitation haw. PMID- 26156162 TI - [A Simultaneous Determination Method with Acetonitrile-n-Hexane Partitioning and Solid-Phase Extraction for Pesticide Residues in Livestock and Marine Products by GC-MS]. AB - A simultaneous determination method was examined for 312 pesticides (including isomers) in muscle of livestock and marine products by GC-MS. The pesticide residues extracted from samples with acetone and n-hexane were purified by acetonitrile-n-hexane partitioning, and C18 and SAX/PSA solid-phase extraction without using GPC. Matrix components such as cholesterol were effectively removed. In recovery tests performed by this method using pork, beef, chicken and shrimp, 237-257 pesticides showed recoveries within the range of 70-120% in each sample. Validity was confirmed for 214 of the target pesticides by means of a validation test using pork. In comparison with the Japanese official method using GPC, the treatment time of samples and the quantity of solvent were reduced substantially. PMID- 26156163 TI - [Determination of Amantadine in Poultry Tissues and Egg by LC-MS/MS]. AB - An accurate and selective analytical method for amantadine, which is used as antiviral drug to treat influenza A virus infection, was developed using LC MS/MS. Residual amantadine was extracted from 4 kinds of food sample (poultry muscle, liver, gizzard and egg) with acetonitrile-pH 3.0 McIlvaine buffer (7 : 3), then cleaned up with an Oasis(r) MCX mini-cartridge. An external standard calibration curve was used for quantification, after sample purification by the combination of a reverse-phase strong cation exchange mixed mode cartridge for cleanup and a HILIC column for HPLC. The method was validated by performing recovery tests in accordance with Japanese guidelines for the validation of analytical methods for residual agricultural chemicals in food. Recovery ranged from 79.3% to 91.7%, RSDs of repeatability were under 3.3%, and RSDs of within laboratory reproducibility were under 8.4%. This new method was applied to samples of poultry and egg purehased in Tokyo, but residual amantadine was not detected at all. PMID- 26156164 TI - [Development of ICP-OES, ICP-MS and GF-AAS Methods for Simultaneous Quantification of Lead, Total Arsenic and Cadmium in Soft Drinks]. AB - In this study, we developed methods to quantify lead, total arsenic and cadmium contained in various kinds of soft drinks, and we evaluated their performance. The samples were digested by common methods to prepare solutions for measurement by ICP-OES, ICP-MS and graphite furnace atomic absorption spectrometry (GF-AAS). After digestion, internal standard was added to the digestion solutions for measurements by ICP-OES and ICP-MS. For measurement by GF-AAS, additional purification of the digestion solution was conducted by back-extraction of the three metals into nitric acid solution after extraction into an organic solvent with ammonium pyrrolidine dithiocarbamate. Performance of the developed methods were evaluated for eight kinds of soft drinks. PMID- 26156165 TI - [Classification of Histopathological Findings in the Liver Cited in the Pesticides Risk Assessment Reports Published by the Food Safety Commission of Japan and Thesaurus Construction Based on the International Harmonization of Nomenclature and Diagnostic (INHAND) Criteria]. AB - Histopathological findings are important to the understanding of toxicity profiles of pesticides. The liver is often a target organ of chemicals. In the present study, histopathological findings in the liver cited in the pesticides risk assessment reports published by the Food Safety Commission of Japan were classified. The histopathological findings were obtained in repeated-dose 90-day oral toxicity studies of mice, rats and dogs and carcinogenicity studies of rodents. After the classification, a thesaurus was constructed based on the International Harmonization of Nomenclature and Diagnostic (INHAND) Criteria. We recommend the use of INHAND criteria in risk assessment reports to improve mutual understanding between applicants and risk assessors. PMID- 26156166 TI - [Application of Coagulant in the Analysis of Lycorine and Galanthamine in Processed Foods]. AB - Analytical method by HPLC and LC-MS/MS for determining lycorine and galanthamine in processed food was newly developed. In this method, coagulant which has never been used in food analysis was applied on cleanup process. With coagulant approach, removal of interfering substances on determination for analytes was easily achieved. The method using HPLC showed recovery of 95.4-102.9% on both analytes with repeatability of less than 2.9% and reproducibility of less than 2.9%. The method using LC-MS/MS showed recovery of 97.4-107.6% with repeatability of less than 5.7% and reproducibility of less than 5.7%. On HPLC method, limit of quantification for lycorine was 0.004 g/kg and that of galanthamine was 0.006 g/kg. On LC-MS/MS method, limit of quantification for lycorine was 0.0008 g/kg and that of galanthamine was 0.0005 g/kg. PMID- 26156167 TI - [Trace Analysis of Lead in Copper Gluconate by Atomic Absorption Spectrometry after Separation by Co-Precipitation with Bismuth]. AB - In order to determine trace amounts of lead in copper gluconate by atomic absorption spectrometry (AAS), the authors investigated a separation and pre concentration procedure using a co-precipitation technique with bismuth. After ashing 2.0 g of the sample by means of a dry process, the ash was dissolved in (1 >100) nitric acid and 75 MUg of bismuth was added. Lead was co-precipitated by using an ammonium solution controlled to pH 9.5-10.5. The precipitate was left at room temperature for over 15 minutes to age, and then washed with a (3->100) ammonium solution three times. The precipitate was dissolved in (1->100) nitric acid and then analyzed by AAS. The quantification limit of this method was 0.5 mg/kg, and the trueness, repeatability and intermediate precision were 99.6%, 4.2% and 4.2% at the spiked concentration of 0.5 mg/kg, and 94.4%, 2.8% and 4.0% at the spiked concentration of 5.0 mg/kg, respectively. Thus, the present method for trace analysis of lead in copper gluconate was validated. PMID- 26156168 TI - Comprehensive Study of Pathogenic Genes Distributed in Escherichia coli Isolated from Cattle. AB - Pathogenic genes such as stx1, stx2, STh gene, STp gene, LT gene, invE, eae, aggR, afaD, astA, cdt and cnf were investigated in Escherichia coli isolated from cattle during Nov. 2012 and Aug. 2013. Plural pathogenic genes were concurrently detected by multiplex PCR, and screen-positive genes were confirmed and sub classified by PCR. Among 100 cattle investigated, 180 E. coli strains with diarrheic genes (DEC) were detected in 79 cattle, and 45 of them, isolated from 32 cattle, were Shiga toxin-producing E. coli (STEC). More than 30% of cattle carried astA, cdt, cnf and stx2 in descending order. STh gene, LT gene, invE, aggR and afaD were not detected in this study. Both stx1 and stx2 were concurrently detected from 6 of 45 STEC strains and stx2 alone was detected from 19. Seventeen STEC strains carried STp gene, astA, or cdt along with stx1 or stx2. Additionally, 135 remaining DEC were classified into 18 enterotoxigenic E. coli with STp gene, 25 enteropathogenic E. coli with eae, and 92 other DEC with astA, cdt and cnf. Both O and H serotypes were identified in 48 strains, including O157 : H7, O1H7 and so on. O157 : H7 were identified in 3 strains that carried stx2 and eae together, as found in human pathogenic strains isolated from patients with gastroenteritis and hemolytic-uremic syndrome. PMID- 26156169 TI - [Interlaboratory Study on Zinc Test for Food-Contact Rubber Products]. AB - Using six kinds of zinc solution in water and 4% acetic acid as samples, an interlaboratory study was performed to evaluate a zinc (Zn) test method for food contact rubber products, based on the Japanese Food Sanitation Law. Eighteen laboratories participated, and quantified Zn in six test solutions as blind duplicates using flame atomic absorption spectrometry, induced coupled plasma optical emission spectrometry or induced coupled plasma-mass spectrometry. Statistical analysis revealed that the trueness, repeatability (RSDr) and reproducibility (RSDr) were 97-103%, 0.7-4.9% and 1.7-8.9% by all measuring methods. The values of the performance parameter fulfilled the target value (trueness: 80-110%, RSDr: 10%, RSDr: 25%). The performance of these methods is sufficient for testing the adherence of samples to the specifications. PMID- 26156170 TI - Acute ischemic stroke in a child due to basilar artery occlusion treated successfully with a stent retriever. AB - Ischemic strokes in childhood are rare. Thrombolytic therapy with intravenous (IV) tissue plasminogen activator (tPA) has been the main intervention for the management of pediatric stroke patients, but safety data are lacking and efficacy has been questioned. Recently, successful endovascular treatments for acute ischemic stroke in children have been reported with increasing frequency, suggesting that mechanical thrombectomy can be a safe and effective treatment. We present the case of a 22-month-old child with acute ischemic stroke due to basilar artery occlusion that was successfully treated with a stent retriever. PMID- 26156171 TI - Spontaneous thrombosis of a basilar tip aneurysm after ventriculoperitoneal shunting. AB - We present a case of a large unruptured basilar tip aneurysm with concomitant hydrocephalus. Complete thrombosis of the aneurysm was observed after ventriculoperitoneal shunting. Analyzing preoperative and postoperative MRI and DSA images, we identified reduced intracranial pressure and widening of the aneurysm-artery inclination angle as possible factors influencing spontaneous thrombosis. To the best of our knowledge, this is the first report of aneurysm thrombosis occurring after CSF diversion. PMID- 26156172 TI - Vertebral-venous fistula: an unusual cause for ocular symptoms mimicking a carotid cavernous fistula. AB - Vertebral-venous fistulas (VVF), or vertebral-vertebral arteriovenous fistulas, are an uncommon clinical entity. Typically, they present as a result of a direct vascular connection between an extracranial branch of the vertebral artery or its radicular components and the epidural venous plexus. These may manifest with signs and symptoms referable to cervical myelopathy secondary to compression or steal phenomenon. To our knowledge, this is the first case to identify a patient who presented with classic ocular symptoms attributable to a carotid cavernous fistula but secondary to a VVF. We present its treatment and clinical outcome. In addition, we present a brief literature review surrounding this uncommon disease. PMID- 26156173 TI - A cold-tolerant evergreen interspecific hybrid of Ocimum kilimandscharicum and Ocimum basilicum: analyzing trichomes and molecular variations. AB - Ocimum (Lamiaceae) is an important source of essential oils and aroma chemicals especially eugenol, methyl eugenol, linalool, methyl chavicol etc. An elite evergreen hybrid has been developed from Ocimum kilimandscharicum and Ocimum basilicum, which demonstrated adaptive behavior towards cold stress. A comparative molecular analysis has been done through RAPD, AFLP, and ISSR among O. basilicum and O. kilimandscharicum and their evergreen cold-tolerant hybrid. The RAPD and AFLP analyses demonstrated similar results, i.e., the hybrid of O. basilicum and O. kilimandscharicum shares the same cluster with O. kilimandscharicum, while O. basilicum behaves as an outgroup, whereas in ISSR analysis, the hybrid genotype grouped in the same cluster with O. basilicum. Ocimum genotypes were analyzed and compared for their trichome density. There were distinct differences on morphology, distribution, and structure between the two kinds of trichomes, i.e., glandular and non-glandular. Glandular trichomes contain essential oils, polyphenols, flavonoids, and acid polysaccharides. Hair like trichomes, i.e., non-glandular trichomes, help in keeping the frost away from the living surface cells. O. basilicum showed less number of non-glandular trichomes on leaves compared to O. kilimandscharicum and the evergreen cold tolerant hybrid. Trichomes were analyzed in O. kilimandscharicum, O. basilicum, and their hybrid. An increased proline content at the biochemical level represents a higher potential to survive in a stress condition like cold stress. In our analysis, the proline content is quite higher in tolerant variety O. kilimandscharicum, low in susceptible variety O. basilicum, and intermediate in the hybrid. Gene expression analysis was done in O. basilicum, O. kilimandscharicum and their hybrid for TTG1, GTL1, and STICHEL gene locus which regulates trichome development and its formation and transcription factors WRKY and MPS involved in the regulation of plant responses to freezing and cold. The analysis showed that O. kilimandscharicum and the hybrid were very close to each other but O. basilicum was more distinct in all respects. The overexpression of the WRKY coding gene showed high expression in the hybrid as compared to O. kilimandscharicum and O. basilicum and the transcription factor microspore specific (MPS) promoter has also shown overexpression in the hybrid for its response against cold stress. The developed evergreen interspecific hybrid may thus provide a base to various industries which are dependent upon the bioactive constituents of Ocimum species. PMID- 26156175 TI - Medicine and philosophy: back to the antiquity. PMID- 26156174 TI - Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model. AB - BACKGROUND: Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. METHODS: In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. RESULTS: We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. CONCLUSION: Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009. PMID- 26156176 TI - Prevention of disease caused by fluoro-edenite fibrous amphibole: the way forward. AB - Few months after the publication of the monographic section of Annali dell'Istituto Superiore di Sanita second issue of 2014 "Health impact of fibres with fluoro-edenitic composition", the carcinogenicity of fluoro-edenite was assessed by the International Agency for Research on Cancer (IARC) in the frame of Monograph 111. The IARC Working Group concluded that there is sufficient evidence in humans that exposure to fluoro-edenite fibrous amphibole causes mesothelioma, and sufficient evidence of carcinogenicity in experimental animals. Fluoro-edenite was allocated to Group 1 (the agent is carcinogenic to humans). Now, in view of the recent IARC evaluation, preventive action in Biancavilla requires an upgrade. First of all, environmental monitoring has to be further implemented. All operations of house cleaning should be performed employing wet tools, in order to avoid dust-raising. It is very important that environmental and biological monitoring be related to epidemiological surveillance. The recently approved act of the Sicilian Government concerning a plan of health interventions in Biancavilla will favour cooperation between national, regional and local health institutions with the common goal of improving the quality and appropriateness of diagnostic and therapeutics procedures offered by the health services. PMID- 26156177 TI - The "Sportello Salute Giovani" project: Habits , lifestyles, risk behaviours of Italian University students and future perspectives. Preface. PMID- 26156178 TI - Study population, questionnaire, data management and sample description. AB - INTRODUCTION: This article describes methodological issues of the "Sportello Salute Giovani" project ("Youth Health Information Desk"), a multicenter study aimed at assessing the health status and attitudes and behaviours of university students in Italy. MATERIALS AND METHODS: The questionnaire used to carry out the study was adapted from the Italian health behaviours in school-aged children (HBSC) project and consisted of 93 items addressing: demographics; nutritional habits and status; physical activity; lifestyles; reproductive and preconception health; health and satisfaction of life; attitudes and behaviours toward academic study and new technologies. The questionnaire was administered to a pool of 12 000 students from 18 to 30 years of age who voluntary decided to participate during classes held at different Italian faculties or at the three "Sportello Salute Giovani" centers which were established in the three sites of the Universita Cattolica del Sacro Cuore (Catholic University of the Sacred Heart of Rome). RESULTS: The final study sample was composed by 8516 university students. The mean age of responders was 22.2 (Standard Deviation 2.0) and 5702 (67.0%) were females. According to the distribution in age classes, 3601 (43.3%) belonged to the 18-21 one, 3796 (44.5%) to the 22-24 class and 1019 (12.2%) to the 25-30 class. With respect to socio-economic status, data were available for 8410 responders and showed that 50.3% of students belonged to the middle class. DISCUSSION: The project took into consideration a large number of individuals from different regions of the country and therefore may be considered representative of the general population of Italian university students. Furthermore, it is the first to address, at the same time, several issues, in particular attitudes and behaviours toward health, in Italian university students. CONCLUSION: The analysis of data from such a large sample of university students sets the basis for identifying the most appropriate interventions in order to address the specific needs of this population. PMID- 26156179 TI - Nutritional habits in Italian university students. AB - INTRODUCTION: Dietary habits have been indicated by research as key elements in both disease pathogenesis and prevention and health promotion. MATERIALS AND METHODS: We analyzed data collected from Italian university students regarding consumption of fruits, vegetables, fast-foods, sweets, energizing drinks, and coffee, average number of eating episodes per day and regularity of breakfast habits. RESULTS: 44% of the university student population eats in average at least 1 portion of fruit per day. 22.5% eats at least 2 portions of vegetables per day. 8.5% eats in average 5 times per day with 48.6% declaring an average of 3 eating episodes per day. 11.3% consumes eccessive amounts of caffeine. 49.1% of the females reaches the recommended consumption of fruit, compared to only 33.8% of males (p < 0.05). 27.7% of females eats at least 2 portions of vegetables per day, compared to 12.0% of males (p < 0.05). Eccessive coffee drinkers pass from 8.9% in the 18-21 age group to 16% in the 25-30 year old age group (p < 0.05). DISCUSSION: This study showed that the eating habits of young adults do not follow national recommendations. Less than 50% of university students eats at least 1 portion of fruit per day and less than 1 out of 4 eats at least 2 portions of vegetables per day. Less than 10% of the students eats in average 5 times per day and more than 1 out of 3 does not have breakfast regularly every morning. CONCLUSION: Interventions targeting university students are required in order to increase their knowledge on healthy eating habits and to ameliorate their dietary behaviours. PMID- 26156180 TI - Physical activity and health promotion in Italian university students. AB - INTRODUCTION: Physical activity, diet plans, the mantainment of a certain Body Mass Index (BMI) and the use of various types of supplementation are common elements in the search for disease prevention, health promotion and well-being. MATERIALS AND METHODS: We analyzed the data regarding Italian university students' BMI, dieting behaviour, personal body perception, exercise habits, and use of dietary supplements and of doping substances. RESULTS: 13.7% resulted being underweight, 75.1% was in the normal range, 9.8% was overweight, and 1.4% was obese. 11.0% were on a diet. 25.8% of the students reported never doing any type of physical activity. 0.9% admitted consuming doping substances. The percentage of overweight/obese students increases from 8.8% of the 18-21 year olds to 18.1% of the 25-30 year olds. Similarly, the prevalence of overweight/obesity was 18.5% among male population and 7.5% among the female one. DISCUSSION: The data deriving from this questionnaire showed that while the majority of university students has a BMI in the normal range, 11.2% of the study population is overweight/obese. Males present a higher risk of being overweight or obese. An important part of the population showed to be sedentary even though data coming from our study are aligned to further evidence. CONCLUSION: The most important concern arising from the questionnaire is represented by physical inactivity. Indeed, it is necessary to encourage and plan initiatives aimed at promoting physical activity in university students. PMID- 26156181 TI - Risky behaviours among university students in Italy. AB - BACKGROUND: The use of psychoactive substances is one of the most important public health issues. Tobacco, alcohol and illicit drugs are among the top risk factors for ill-health defined by World Health Organisation. The risky behaviours acquired in teenage can be magnified or decreased during university when a person starts having more awareness about the importance of own wellness. This paper describes the results of the project "Sportello Salute Giovani" ("Youth Health Information Desk") with respect to risky behaviours in a large sample of Italian university students. MATERIALS AND METHODS: 18 questions of the survey "Sportello Salute Giovani" dealing with risky behaviors, the use of psychoactive substances such as tobacco, alcohol and illicit drugs were included. Absolute and relative frequencies were calculated. Besides, chi square test were used to test the differences in sex, age class and socio-economic status. RESULTS: About 24% of the interviewed students currently smokes. 89% and 42.2% respectively drinks at least rarely or weekly beer, wine or spirits. About 40% of students smoked at least a joint and about 2% used other drugs (mostly cocaine). CONCLUSION: The "Sportello Salute Giovani" survey suggests that the frequency of risky behaviours in Italian university students is not reassuring, although they should be aware about the negative consequences on their and others health because of their educational level. PMID- 26156182 TI - Italian university students' self-perceived health and satisfaction of life. AB - INTRODUCTION: Health is defined as a state of complete physical, social and mental well-being, therefore, it should not be considered as simply the absence of disease. In this light, the assessment of self-perceived health and life satisfaction plays an important role as it allows addressing the subjective perception of physical health, as well as mental health and social functioning. MATERIAL AND METHODS: This study analyzed data from 8516 university students enrolled in the "Sportello Salute Giovani" project ("Youth Health Information Desk"). In particular, it addressed self-perceived health and life satisfaction, reported somatic and psychological symptoms and ability to cope with daily problems of university students from 18 to 30 years old. RESULTS: Overall, 77.1% of students declared to have a good or very good health and the mean score of life satisfaction was 7.46. In respect to somatic and psychological symptoms, 25.8% of students reported to suffer almost daily of at least one among headache, stomach pain, back pain, tiredness, nervousness, dizziness and troubles falling asleep. Results varied on the basis of sex, with women showing lower self perceived health compared to men and reporting more symptoms. Furthermore, self perceived health was shown better in younger students and in those belonging to higher socio-economic level. DISCUSSION: The survey showed that concern exists with respect to university students' self-perceived health, which is different from that arising from other evidence. Female students had a significant lower self-perceived health and reported somatic and psychological symptoms more commonly than men. On the other hand, results about life satisfaction seem to be aligned with the literature. CONCLUSION: One of the most important implications of the study is the need to address self-perceived health and reported symptoms in university students in order to monitor them and initiate interventions aimed at improving well-being and controlling inequalities. PMID- 26156183 TI - Study habits and technology use in Italian university students. AB - BACKGROUND: Students' ability of learning is influenced by study habits. Among these, the use of technologies has assumed a controversial role. The aim of this paper is to analyse studying approach, the use of technologies and how they affect study habits in a population of university students addressed by the "Sportello Salute Giovani" ("Youth Health Information Desk") questionnaire. METHODS: 16 questions referred to the approach to studying and the use of technologies (number 77-93) were analyzed. Absolute and relative frequencies were calculated. Stratification for sex, age and socio-economic status were performed and Chi square test was used to test the difference between sex, age class and socio-economic groups. RESULTS: 99.7% of students declared to have at least one mobile phone and 68.7% to use smartphones, i-phones and i-pads. Males (20.9% vs 14.9% female, p < 0.05), older students (31.7% among 25-30 years old students vs 21.3% among 18-21 years old, p < 0.05) and students with the highest socio economic level (87.8% vs 54.2% of the lowest) seem more likely to use digital technologies/Internet for educational purposes. CONCLUSION: Our survey revealed that most college students still prefer approach the study using books instead of digital tools, but this attitude is conflicting with how many hours they use computers and surf Internet per weeks. Therefore, further studies are needed to understand better technology influence on study habits and its implication on health. PMID- 26156184 TI - Appropriateness of clinical and organizational criteria for intra-articular injection therapies in osteoarthritis. A Delphi method consensus initiative among experts in Italy. AB - OBJECTIVE: The aim of the study was to identify the main aspects involved in patient selection, the choice of therapeutic agents and the safety profile, as well as the medico-legal and organizational aspects of intra-articular injection therapies for osteoarthritis. METHODS: A committee of 10 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Fifty-two clinicians from a large number of Italian medical centers specialized in intra-articular injection therapy took part in a Delphi process aimed at obtaining consensus statements among the participants. RESULTS: Large consensus was obtained for statements grouped under the following main themes: treatment indications; drug/medical device choice; treatment efficacy; and appropriate setting. CONCLUSIONS: The consensus statements developed by a large number of experts may be used as a practical reference tool to help physicians treat osteoarthritis patients by means of intra articular injection therapies. PMID- 26156185 TI - Migratory behaviour of tumour cells: a scanning electron microscopy study. AB - BACKGROUND: Tumour cells utilize different migration strategies to invade surrounding tissues and elude anticancer treatments. It is therefore important to understand the mechanisms underlying migration process, in order to aid the development of therapies aimed at blocking the dissemination of cancer cells. AIMS: In this study tumour cell lines of different histological origin were analysed by combining 2D and 3D in vitro assays, biochemical tests and high resolution imaging by scanning electron microscopy (SEM) in order to look insight strategies adopted by tumour cells to invade extracellular matrix. RESULTS: Quantitative (computer-assisted colour camera equipped-light microscopy) and qualitative analysis (SEM) indicated that the most aggressive tumour cells adopt an "individual" behaviour. The analysis of intracellular signalling demonstrated that the highest invasive potential was associated with the activation of AKT, ERK, FAK and ERM proteins. The "individual" behaviour was positively related to the expression of VLA-2 and inversely related with the E-cadherin expression. CONCLUSIONS: The combination of 2D and 3D in vitro assays, biochemical tests and ultrastructural investigations proved to be a suitable test for the investigation of tumour cell migration and invasion. The high resolution imaging by SEM highlighted the interrelationships between cells in different migratory behaviours of tumour cells. PMID- 26156186 TI - Prevalence of major cardiovascular risk factors among oil and gas and energy company workers. AB - INTRODUCTION: Cardiovascular diseases (CVD) remain the biggest cause of disability and premature death throughout the world. AIM: The aim of this study was to describe and determine the prevalence of major cardiovascular risk factors emerged at the first medical examination carried out by a group of an oil and gas contractor company workers in the observation period 2000-2010. METHODS: An observational cross-sectional study was conducted on 1073 workers (mean age 41 years, SD = 9.5) presenting overweight BMI (body mass index) values, hypertension and cholesterol problems. RESULTS: In particular, we found that workers > 45 years had significant higher risk to have obesity (OR = 3.8, CI 95% = 2.5-5.7), hypertension (OR = 2.7, CI 95% = 2.1-3.6), high blood fasting glucose (OR = 2.6, CI 95% = 1.2-5.5), high cholesterol (OR = 2.7, CI 95% = 2.0-3.6), high triglycerides (OR = 1.8, CI 95% = 1.4-2.4) compared to younger (< 45 years). PMID- 26156187 TI - Assessment of lifestyle and eating habits among undergraduate students in northern Italy. AB - AIM AND METHODOLOGY: Dietary habits of university students were analyzed in order to investigate any differences between students living at and away from home. Two hundred and fifty-eight undergraduate students attending University of Ferrara completed a self-administered questionnaire on demographic characteristics, food frequency consumption habits and body weight perception. RESULTS: Students living at home practiced more sport and consumed more frequently raw and cooked vegetables, fish, meat and poultry, fresh fruit, eggs, bread/cereals. Conversely, students living away from home consumed more often packaged/ready food, beer and spirits, milk and chips. The majority of students living alone reported a modification of dietary habits since leaving family. Furthermore they perceived to have a weight condition different from normal in a greater extent than students living with family. DISCUSSION: Students living alone encountered more difficulties in adopting a healthy diet so it would be desirable to adopt nutritional educational interventions on university students, usually neglected by these measures. PMID- 26156188 TI - Cesarean section on maternal request: should it be formally prohibited in Italy? AB - BACKGROUND: Cesarean section on maternal request (CSMR) could represent an avoidable quota of cesareans. In Italy, this is a topical problem of health policy, involving ethical, juridical and medical issues. AIM AND METHODS: A 5 questions questionnaire to quantitatively assess the perspectives of medical, juridical and ethical issues of planned CSMR was administered to obstetricians and gynecologists, midwives, lawyers and pregnant women. It was assessed to what extent those issues matter on the final decision of planning a CSMR. RESULTS: Non homogeneous answers of stakeholders suggest different perspectives about issues on CSMR. The juridical issue seems to have the greatest impact on the final decision. CONCLUSION: Planning a CSMR associates overall with juridical issues in each group of respondents. Therefore, an obstetrician and gynecologist is unable to counsel a patient on CSMR from a medical point of view. The most direct way for reducing cesareans in Italy could be the formal prohibition of CSMR. PMID- 26156189 TI - Biomarkers of effect in endocrine disruption: how to link a functional assay to an adverse outcome pathway. AB - The development of in vitro testing strategies may achieve a cost-effective generation of comprehensive datasets on a large number of chemicals, according to the requirements of the European Regulation REACH. Much emphasis is placed on in vitro methods based on subcellular mechanisms (e.g., nuclear receptor interaction), but it is necessary to define the predictive value of molecular or biochemical changes within an adverse outcome pathway (AOP). AOP pivots on the description of the flow from a molecular initiating event through a cascade of intermediate events needed to produce a specific adverse effect at organism level: downstream responses at cell level are, therefore, essential to define an AOP. Several in vitro assays are based on human cell lines representative of endocrine-targeted tissues (e.g., prostate) and on functional biomarkers of clinical relevance (e.g., PSA secretion in human prostate epithelial cells). We discuss the implementation of such functional biomarkers in the AOP context. PMID- 26156190 TI - Sexual behaviours and preconception health in Italian university students. AB - INTRODUCTION: Risky sexual behaviours have been recognized as a threat for sexual and reproductive health. AIM: This article shows the results of the "Sportello Salute Giovani" project ("Youth Health Information Desk") in relation to determining how a large sample of university students in Italy cope with preconception health, especially in the domains of sexual transmitted infections (STIs), fertility and vaccination preventable disease. METHODS: Twentythree questions of the "Sportello Salute Giovani" survey about sexual behaviour and reproductive health were analysed. Besides, results were stratified for sex, age class and socio-economic status. RESULTS: 19.7% of students have had first sexual intercourse before age 15. 21.8% of female students used emergency contraception. 66.4% of the 74.0% sexual active students reported using contraceptives, but about 32% of them used methods ineffective against STIs. A general low coverage for rubella, measles and mumps vaccination was revealed. 63.7% of men and 30.9% of woman never had urologic or gynaecological examinations. DISCUSSION: Overall, young adults in Italy are not still enough sensitized on fertility and preconception care. High schools and universities should increase awareness towards preservation of male and female fertility and preconception care. PMID- 26156191 TI - Reduced Voluntary Activation During Brief and Sustained Contractions of a Hand Muscle in Secondary-Progressive Multiple Sclerosis Patients. AB - BACKGROUND: Secondary-progressive multiple sclerosis (SPMS) patients have structural cortical damage resulting in increased compensatory cortical activity during (submaximal) performance. However, functional effects of changed cortical output are difficult to measure. The interpolated-twitch technique allows for measurement of voluntary activation (VA) necessary for force production. This study aimed to determine VA, force, and muscle fatigue during brief and sustained contractions in SPMS patients. Because fatigue effects are not confined to the motor system, we additionally examined fatiguing effects on cognitive performance. METHODS: Twenty-five SPMS and 25 sex-, age-, and education-matched participants performed brief (5 seconds) and sustained (2 minutes) maximal index finger abductions. To evaluate VA, double-pulse twitches were evoked before, during, and after contractions. Additionally, data were compared with data obtained in relapsing-remitting multiple sclerosis (RRMS) patients. Subjects also performed choice-reaction time tasks before and after the sustained contraction. RESULTS: During brief contractions, VA (85% vs 94%,P= .004) and force (25 N vs 32 N,P= .011) were lower for SPMS patients than controls. During sustained contractions, VA (P= .001) was also lower, resulting in greater force decline (73% vs 63%,P< .001) and reduced peripheral fatigue (19% vs 50%,P< .001). Comparisons with RRMS resulted in lower VA, greater force decline, and greater estimated central fatigue in SPMS. SPMS patients were slower (P< .001) and made more errors (P< .001) than controls, but neither group reduced their performance after the sustained contraction. CONCLUSION: SPMS patients had lower VA than RRMS patients and controls. The importance of voluntary activation for muscle force and fatigability warrants targeted rehabilitation strategies. PMID- 26156192 TI - Predictive Value of Upper Limb Muscles and Grasp Patterns on Functional Outcome in Cervical Spinal Cord Injury. AB - OBJECTIVE: To determine which single or combined upper limb muscles as defined by the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI); upper extremity motor score (UEMS) and the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP), best predict upper limb function and independence in activities of daily living (ADLs) and to assess the predictive value of qualitative grasp movements (QlG) on upper limb function in individuals with acute tetraplegia. METHOD: As part of a Europe-wide, prospective, longitudinal, multicenter study ISNCSCI, GRASSP, and Spinal Cord Independence Measure (SCIM III) scores were recorded at 1 and 6 months after SCI. For prediction of upper limb function and ADLs, a logistic regression model and unbiased recursive partitioning conditional inference tree (URP-CTREE) were used. Results: Logistic regression and URP-CTREE revealed that a combination of ISNCSCI and GRASSP muscles (to a maximum of 4) demonstrated the best prediction (specificity and sensitivity ranged from 81.8% to 96.0%) of upper limb function and identified homogenous outcome cohorts at 6 months. The URP-CTREE model with the QlG predictors for upper limb function showed similar results. CONCLUSION: Prediction of upper limb function can be achieved through a combination of defined, specific upper limb muscles assessed in the ISNCSCI and GRASSP. A combination of a limited number of proximal and distal muscles along with an assessment of grasping movements can be applied for clinical decision making for rehabilitation interventions and clinical trials. PMID- 26156193 TI - Characterization and evaluation of phosphate microsensors to monitor internal phosphorus loading in Lake Erie sediments. AB - Monitoring phosphate concentration is very important to prevent and control eutrophication in natural waters. In this study, cobalt-based microsensors were modified, characterized, and tested to monitor internal soluble phosphorous (SRP) loading in lakes with improved detection limits. The effectiveness of surface modification on the performance of a cobalt-based microelectrode was fully examined by determining detection limit, response time, selectivity, interference with ions (sulfate, nitrate, and nitrite) and dissolved oxygen (DO). To assess their performance, phosphate sensors were applied to sediment samples collected from Lake Erie. SRP loading from sediments was determined under different DO conditions. After increasing the phosphate sensing area and modifying the surface, phosphate microsensors showed an increased detection limit of up to 10( 8) M concentration of phosphate ion. The phosphate microsensor also showed its ability to measure sediment SRP profiling without disturbing sediment structure, and diffusion coefficients of phosphate in sediment could be determined under both oxic and anoxic conditions. Modified phosphate sensors showed improved sensitivity and could be applied to both water and sediment samples with high spatial resolution; however, signal interferences (especially with oxygen) required consideration during sample analysis. Overall, obtained results showed that phosphate microsensors can be an effective tool for measurement of phosphate in lake water and sediment samples for SRP monitoring. PMID- 26156194 TI - The Outcomes and Quality of Life of Patients with Achalasia after Peroral Endoscopic Myotomy in the Short-Term. AB - PURPOSE: To assess the short-term efficacy and quality of life (QOL) of patients with achalasia after peroral endoscopic myotomy (POEM). METHODS: Thirty-five achalasia patients underwent POEM from May 2013 to December 2013. The data on clinical evaluation and QOL before therapy, at 1 month and 6 months postoperation were collected and analyzed. RESULTS: All the thirty-five patients underwent POEM successfully. By comparing the data of the preoperative with that of 1 month and 6 months after POEM respectively, we found that: mean Eckardt score decreased (6.83 vs 0.51, 6.83 vs 0.46, all P <0.05), esophagus diameter reduced (47.97 mm vs 32.00 mm, 47.97 mm vs 28.50 mm, all P <0.05), and esophageal manometry declined (29.5 mmHg vs 11.5 mmHg, 29.5 mmHg vs 10.3 mmHg, all P <0.05). Complications occurred in 14.3% (5/35) of the cases, and no recurrence was observed. At each time point, postoperative QOL scores were higher than those of preoperative (P <0.05). CONCLUSIONS: POEM is safe and effective for treating achalasia in the short-term, it can relieve clinic symptoms as well as improve patients' QOL. PMID- 26156195 TI - Primary cardiac solitary fibrous tumors. AB - Primary cardiac solitary fibrous tumors were reviewed. They are classified as pericardial tumors. Their incidences are very rare. Only 16 cases were reported in the literature. Basically, surgical treatments are performed. Their prognoses are generally good, although malignant cases are also reported. PMID- 26156196 TI - Protein Interfaces as Targets in Drug Discovery. PMID- 26156197 TI - The Dynamics of Drug Discovery. AB - Proteins are not static objects. To carry out their functions in the cells and participate in biochemical interaction networks, proteins have to explore different conformational substates, which favor the adaptation to different partners and ultimately allow them to respond to changes in the environment. In this paper we discuss the implications of including the atomistic description of protein dynamics and flexibility in the context of drug discovery and design. The underlying idea is that a better understanding of the atomistic details of molecular recognition phenomena and conformational cross-talk between a ligand and a receptor can in fact translate in unexplored opportunities for the discovery of new drug like molecules. We will illustrate and discuss dynamics based pharmacophores, the discovery of cryptic binding sites, the characterization and exploitation of allosteric regulation mechanisms and the definition of potential protein-protein interaction sites as potential sources of new bases for the rational design of small molecules endowed with specific biological functions. Overall, the inclusion of protein flexibility in the drug discovery process is starting to attract attention not only in the academic but also in the industrial community. This is supported by experimental tests that prove the actual feasibility of considering the explicit dynamics of drug-protein interactions at all relevant levels of resolution and the use of multiple receptor conformations in drug discovery, as affordable complements (if not an alternative) to classical High Throughput Screening (HTS) efforts based on static structures. PMID- 26156198 TI - Genotoxic and cytotoxic effects and gene expression changes induced by fixed orthodontic appliances in oral mucosa cells of patients: a systematic review. AB - CONTEXT: The accumulation of chronic or severe acute DNA and cellular damage in oral mucosa cells is one of the main factors that help initiate a wide range of malignant lesions in the oral cavity. There has been considerable controversy in the literature about the effect of such sustained genotoxic and cytotoxic damage to oral mucosa cells. OBJECTIVE: The aim of this systematic review, reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, is to investigate the effects of such interventions. METHODS: Electronic and manual searches were performed (15 May 2015) for Randomized Clinical Trials/quasi-Randomized Clinical Trials that analyzed the genotoxic/cytotoxic effects of these types of oral appliances in humans. A primary outcome (cell/DNA damage) and a number of secondary outcomes were examined. Two reviewers carried out the study selection and performed a "risk of bias" assessment [Cochrane Collaboration's tool]. Wherever possible the meta-analysis was conducted on homogenous groups. RESULTS: From the electronic search (2797), 6 studies met the eligibility criteria. Most studies (5/6) observed significant differences in most comparisons at the short-term (1-3 months) and long-term (24-48 months) evaluations, with respect to critically acute genotoxic/cytotoxic effects. Some of the studies (2/3) concluded that the post-removable effects at DNA/cellular levels were not significant (p > 0.05) with respect to the controls. CONCLUSIONS: Acute DNA/cellular damage in oral mucosa cells is induced by orthodontic appliances. Nevertheless, even though these effects were no longer detected after removing the appliances, more rigorous RCTs are needed to explore the extent to which acquired damage can be observed in the oral mucosa. PMID- 26156199 TI - Association of Alpha-Soluble NSF Attachment Protein with Epileptic Seizure. AB - Alpha-soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (alphaSNAP) is a ubiquitous and indispensable component of membrane fusion machinery. There is accumulating evidence that mild alterations of alphaSNAP expression may be associated with specific pathological conditions in several neurological disorders. This study aimed to assess alphaSNAP expression in temporal lobe epilepsy (TLE) patients and pilocarpine-induced rat model and to determine whether altered alphaSNAP expression leads to increased susceptibility to seizures. The expression of alphaSNAP was assessed in the temporal lobe from patients with TLE and pilocarpine-induced epileptic rats. In addition, alphaSNAP expression was silenced by lentivirus pLKD-CMV-GFP-U6-NAPA (primer: GGAAGCATGCGAGATCTATGC) in animals. At day 7, the animals were kindled by pilocarpine and then the time of latency to seizure and the incidence of chronic idiopathic epilepsy seizures were assessed. The immunoreactivity to alpha-SNAP was utilized to measure expression of this protein in the animal. By immunohistochemistry, immunofluorescence, and western blotting, we found significantly lower alphaSNAP levels in patients with TLE. alphaSNAP expression showed no obvious change in pilocarpine-induced epileptic rats, from 6 h to 3 days after seizure, compared with the control group, in the acute stage; however, alphaSNAP levels were significantly lower in the chronic phase (day 7, months 1 and 2) in epileptic rats. Importantly, behavioral data revealed that alphaSNAP small interfering RNA (siRNA) could decrease the time of latency to seizure and increase the incidence of chronic idiopathic epilepsy seizures compared with the control group. alphaSNAP is mainly expressed in the neuron brain tissue of patients with TLE and epileptic animals. Our findings suggest that decreasing alphaSNAP levels may increase epilepsy susceptibility, providing a new strategy for the treatment of this disease. PMID- 26156200 TI - Effects of a Terrified-Sound Stress on Serum Proteomic Profiling in Mice. AB - The serum proteomic profiles of mice exposed to terrified-sound-induced stress and after stress release were investigated. Serum samples from 32 mice were divided into four groups (n = 8 each) and analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry techniques (MALDI-TOF MS) combined with magnetic bead-based weak cation-exchange chromatography. ClinProTools software identified several distinct markers that differed between the stressed and control groups and between the stress released and stressed released controls. Of 33 m/z peaks that differed among the four groups, 17 were significantly different (P < 0.05). Five peaks (m/z: 2793.37, 2924.86, 1979.90, 3492.49, 3880.24) showed significant differences in expression after exposure to terrified-sound stress and returned to control levels after stress release. These were sequence identified as peptide regions of dimethylaniline monooxygenase, myosin-9, uncharacterized protein in Rattus norvegicus, apolipoprotein C-I, and plasma serine protease inhibitor (Serpina 5). Our study provides the first evidence of significant changes in serum proteomic profiles in mice exposed to terrified-sound stress, which suggests that protein expression profiles are affected by the stress. Normal expression levels were restored after stress release, suggesting the activation of self-adjustment mechanisms for the recovery of protein expression levels altered by this stress. PMID- 26156201 TI - RIP1 Inhibition Rescues from LPS-Induced RIP3-Mediated Programmed Cell Death, Distributed Energy Metabolism and Spatial Memory Impairment. AB - Receptor interacting protein 1 (RIP1) has a critical role in initiation of programmed necrosis or necroptosis. RIP1 in a close collaboration with RIP3 not only mediates necroptosis but also is involved in apoptosis and inflammatory signaling. However, the interpretation of the distinct function of RIP1 and RIP3 is complicated. Herein, we demonstrated that RIP1 inhibition in the context of LPS-induced neuroinflammation decreases RIP3 expression. Concomitant administration of Nec-1, specific inhibitor of RIP1, with LPS also attenuated the activating effect of RIP3 on metabolic enzymes, glutamate-ammonia ligase and glutamate dehydrogenase as bioenergetic determinants, in hippocampal and cortical cells. RIP1 inhibition possessed an anti-inflammatory effect and improved the antioxidant capacity against LPS. Interestingly, and opposed to some reports that necroptosis inhibition sensitizes cells to apoptosis, our results showed that RIP1 inhibition attenuates apoptotic cell death in response to LPS. The survival of neuronal function was also confirmed by measuring spontaneous alternations of rats in Y-maze. In conclusion, effects of RIP1 inhibition on RIP3 and cell death provide new approaches to ameliorate neuroinflammation and relative disorders. PMID- 26156202 TI - Gene Variant and Level of IL-1beta in Ischemic Stroke Patients With and Without Type 2 Diabetes Mellitus. AB - Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to explore, for the first time, the relationship between IL-1beta -31 T/C polymorphism and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). One hundred ninety-six patients with IS (117 diabetics and 79 nondiabetics) and 192 controls were recruited to enroll in this study. IL-1beta genotyping was performed by PCR RFLP technique. After adjusting for sex, age, smoking, obesity, dyslipidemia, and hypertension, there was no significant difference in the distribution of IL-1beta -31 T/C genotypes and allele frequencies between IS patients with or without type 2 diabetes mellitus and control group (p > 0.05). Moreover, a significant positive correlation between serum IL-1beta level and glucose (p1 = 0.044) was showed. In addition, serum levels of IL-1beta were found to be higher among TT genotype carriers than TC and CC genotype carriers in ischemic stroke patients with or without T2DM but these differences were not significant. These results indicate that IL-1beta gene polymorphism might not be a risk factor in the development of ischemic stroke in Tunisian population. PMID- 26156203 TI - Accessing disability services by people from culturally and linguistically diverse backgrounds in Australia. AB - PURPOSE: To examine whether differences in access to specialist disability services by people from culturally and linguistically diverse (CALD) backgrounds when compared with those born in Australia represent a service gap or the healthy migrant effect. METHOD: To use the latest disability statistics to measure the different rates of people with disability, and the rates of people with profound and severe disability, of people born in Australia and those born abroad; to compare the difference between those who mainly speak English with those who primarily speak a language other than English at home (LOTE); and examine the age specific and standardised disability rates of these subgroups. RESULTS: The rate of access of specialist disability services by people with disability who were from CALD backgrounds is highly disproportionate to their presence in the community. As a whole, people from CALD backgrounds have a similar level of disability as Australia-born people. They have a greater rate of profound and severe disability and a higher level of need for assistance in undertaking core activities. For younger age cohorts targeted by specialist disability services, there is little difference in the level of need for assistance between people from CALD backgrounds and the rest of community. Those people who mainly speak LOTE at home have a relatively higher level of need for assistance than those who speak mainly English at home. CONCLUSIONS: The paper reveals a substantial gap in specialist disability services between people from CALD and the broader community. This cannot be explained by the difference in the level of need for assistance between Australia-born and overseas-born populations, therefore raises some policy questions as to the barriers to the use of such services and how to effectively narrow the service access gap and improve utilisation rates. IMPLICATIONS FOR REHABILITATION: The paper reveals a substantial accessibility gap in specialist disability services between people from culturally and linguistically diverse (CALD) backgrounds and the broader community in Australia. Rehabilitation is a large component of disability services. Therefore, understanding the gap, promoting the awareness of the services, developing appropriate and effective services to respond the need of people with disability from CALD backgrounds, are critically important to rehabilitation services and related research. PMID- 26156204 TI - Kleiber's Law: How the Fire of Life ignited debate, fueled theory, and neglected plants as model organisms. AB - Size is a key feature of any organism since it influences the rate at which resources are consumed and thus affects metabolic rates. In the 1930s, size dependent relationships were codified as "allometry" and it was shown that most of these could be quantified using the slopes of log-log plots of any 2 variables of interest. During the decades that followed, physiologists explored how animal respiration rates varied as a function of body size across taxa. The expectation was that rates would scale as the 2/3 power of body size as a reflection of the Euclidean relationship between surface area and volume. However, the work of Max Kleiber (1893-1976) and others revealed that animal respiration rates apparently scale more closely as the 3/4 power of body size. This phenomenology, which is called "Kleiber's Law," has been described for a broad range of organisms, including some algae and plants. It has also been severely criticized on theoretical and empirical grounds. Here, we review the history of the analysis of metabolism, which originated with the works of Antoine L. Lavoisier (1743-1794) and Julius Sachs (1832-1897), and culminated in Kleiber's book The Fire of Life (1961; 2. ed. 1975). We then evaluate some of the criticisms that have been leveled against Kleiber's Law and some examples of the theories that have tried to explain it. We revive the speculation that intracellular exo- and endocytotic processes are resource delivery-systems, analogous to the supercellular systems in multicellular organisms. Finally, we present data that cast doubt on the existence of a single scaling relationship between growth and body size in plants. PMID- 26156205 TI - Changes in urodynamic measurements and bladder neck position after single incision trans-vaginal mesh for pelvic organ prolapse. AB - INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is common in patients with pelvic organ prolapse. This study hypothesized that SUI may be persistent, de novo, or even cured in women after ElevateTM mesh repair alone and that SUI is associated with urodynamic changes and bladder neck position. METHODS: This secondary analysis included a study cohort of 100 women who underwent Elevate repair. All of them underwent multi-channel urodynamic measurements, 1-h pad test, and bead chain urethrocystography to measure the bladder neck position pre-operatively and at 3 months post-surgery. RESULTS: Fifty-five women with pelvic organ prolapse were continent and 45 had concomitant SUI. Of the 55 continent women, 19 (35%) had de novo SUI after mesh repair surgery and 5 (9%) subsequently underwent anti-incontinence surgery. Of the 45 incontinent women, 11 (24%) became dry after mesh repair without additional anti incontinence surgery. Of the remaining 34 (76%) with persistent SUI, 15 (33%) underwent subsequent anti-incontinence surgery. Patients with de novo and persistent SUI had a greater decrease in maximal urethral closure pressure (MUCP) after mesh repair (p = 0.03 and 0.01 respectively). Those cured of SUI also had decreased MUCP (p = 0.12), but the bladder neck position while straining was significantly more elevated after mesh repair (p < 0.01) compared with those with persistent SUI. CONCLUSIONS: Elevate mesh reinforcement significantly decreases post-operative MUCP, which is associated with SUI, but can elevate the bladder neck position. Correcting a hyper-mobile urethra is associated with treatment of the concomitant SUI. PMID- 26156206 TI - Sacral neuromodulation: an effective treatment for lower urinary tract symptoms in multiple sclerosis. AB - INTRODUCTION AND HYPOTHESIS: Most subjects with multiple sclerosis (MS) suffer from lower urinary tract symptoms (LUTS). Detrusor overactivity, detrusor hypocontractility and detrusor-sphincter dyssynergia are the most common bladder dysfunctions. Management is not straightforward due to the progressive course of the disease. Sacral neuromodulation (SNM) has received increasing attention among new effective treatments for bladder disorders associated with MS. The aim of this study was to review the published literature on the role of SNM in the treatment of LUTS in patients with MS. METHODS: A literature search was carried out up to December 2014, using relevant search terms in MEDLINE and EMBASE databases. The ClinicalTrials.gov and Controlled-trials.com online trial registries and the abstracts from international scientific meetings were searched for English-language studies containing relevant search terms. Relevant reviews and trials and prospective studies were analysed by two independent reviewers. RESULTS: Two prospective studies and four retrospective studies were included. Overall, MS patients represented small series (4 to 25 subjects). The longest follow-up was 7 years and the evaluation of the treatment outcomes was not homogeneous among the studies. The definition of objective cure was often unclear. The subjective cure rate was 45 %, patients' reported satisfaction was 85 % and all the results were stable over time. CONCLUSIONS: SNM seems to be a safe and effective treatment for LUTS in MS patients. Further and larger studies as well as randomized controlled trials are needed to confirm its clinical role in patients with MS. PMID- 26156207 TI - Facile Preparation of Core-Shell Magnetic Metal-Organic Framework Nanoparticles for the Selective Capture of Phosphopeptides. AB - In regard to the phosphoproteome, highly specific and efficient capture of heteroideous kinds of phosphopeptides from intricate biological sample attaches great significance to comprehensive and in-depth phosphorylated proteomics research. However, until now, it has been a challenge. In this study, a new fashioned porous immobilized metal ion affinity chromatography (IMAC) material was designed and fabricated to promote the selectivity and detection limit for phosphopeptides by covering a metal-organic frameworks (MOFs) shell onto Fe3O4 nanoparticles, taking advantage of layer-by-layer method (the synthesized nanoparticle denoted as Fe3O4@MIL-100 (Fe)). The thick layer renders the nanoparticles with perfect hydrophilic character, super large surface area, large immobilization of the Fe(3+) ions and the special porous structure. Specifically, the as-synthesized MOF-decorated magnetic nanoparticles own an ultra large surface area which is up to 168.66 m(2) g(-1) as well as two appropriate pore sizes of 1.93 and 3.91 nm with a narrow grain-size distribution and rapid separation under the magnetic circumstance. The unique features vested the synthesized nanoparticles an excellent ability for phosphopeptides enrichment with high selectivity for beta-casein (molar ratio of beta-casein/BSA, 1:500), large enrichment capacity (60 mg g(-1)), low detection limit (0.5 fmol), excellent phosphopeptides recovery (above 84.47%), fine size-exclusion of high molecular weight proteins, good reusability, and desirable batch-to-batch repeatability. Furthermore, encouraged by the experimental results, we successfully performed the as-prepared porous IMAC nanoparticle in the specific capture of phosphopeptides from the human serum (both the healthy and unhealthy) and nonfat milk, which proves itself to be a good candidate for the enrichment and detection of the low-abundant phosphopeptides from complicated biological samples. PMID- 26156208 TI - Potential chemotherapeutic targets for Japanese encephalitis: current status of antiviral drug development and future challenges. AB - INTRODUCTION: Japanese encephalitis (JE) remains a public health threat in Asia. Although several vaccines have been licensed, ~ 67,900 cases of the disease are estimated to occur annually, probably because the vaccine coverage is low. Therefore, effective antiviral drugs are required to control JE. However, no licensed anti-JE drugs are available, despite extensive efforts to develop them. AREAS COVERED: We provide a general overview of JE and JE virus, including its transmission cycle, distribution, structure, replication machinery, immune evasion mechanisms and vaccines. The current situation in antiviral drug development is then reviewed and future perspectives are discussed. EXPERT OPINION: Although the development of effective anti-JE drugs is an urgent issue, only supportive care is currently available. Recent progress in our understanding of the viral replication machinery and immune evasion strategies has identified new targets for anti-JE drug development. To date, most candidate drugs have only been evaluated in single-drug formulations, and efficient drug delivery to the CNS has virtually not been considered. However, an effective anti-JE treatment is expected to be achieved with multiple-drug formulations and a targeted drug delivery system in the near future. PMID- 26156209 TI - A Computational Approach for Designing a Universal Epitope-Based Peptide Vaccine Against Nipah Virus. AB - Nipah virus (NiV) is highly pathogenic single-stranded negative sense RNA virus. It can cause severe encephalitis and respiratory disease in humans. In addition, NiV infects a large range of host including mammals. As a result of its higher zoonotic potential and pathogenicity for human, it has been rated as an alert in recent days. A therapeutic treatment or vaccines has become elusive to fight against this virus. In this study, the attachment (G) and fusion (F) glycoproteins of NiV, responsible for the viral attachment and entry to the host cell, were selected to develop epitope-based vaccine against Nipah virus. Epitopes were identified from the conserved region of G and F protein of NiV. Both B-cell and T-cell immunity were checked to affirm it that these epitopes will be able to induce humoral and cellular immunity. A total of 6 T-cell epitopes and 19 significant HLA-epitope interactions were identified. Eventually it has shown an acceptable percentage in population coverage (46.45 %) and efficient binding with HLA molecule by molecular docking study. PMID- 26156210 TI - Web-Based Study of Risk Factors for Pain Exacerbation in Osteoarthritis of the Knee (SPARK-Web): Design and Rationale. AB - BACKGROUND: Knee osteoarthritis (OA) is the most frequent cause of limited mobility and diminished quality of life. Pain is the main symptom that drives individuals with knee OA to seek medical care and a recognized antecedent to disability and eventually joint replacement. Many persons with symptomatic knee OA experience recurrent pain exacerbations. Knowledge and clarification of risk factors for pain exacerbation may allow those affected to minimize reoccurrence of these episodes. OBJECTIVE: The aim of this study is to use a Web-based case crossover design to identify risk factors for knee pain exacerbations in persons with symptomatic knee OA. METHODS: Web-based case-crossover design is used to study persons with symptomatic knee OA. Participants with knee pain and radiographic knee OA will be recruited and followed for 90 days. Participants will complete an online questionnaire at the baseline and every 10 days thereafter (totaling up to 10 control-period questionnaires); participants will also be asked to report online when they experience an episode of increased knee pain. Pain exacerbation will be defined as an increase in knee pain severity of two points from baseline on a numeric rating scale (NRS 0-10). Physical activity, footwear, knee injury, medication use, climate, psychological factors, and their possible interactions will be assessed as potential triggers for pain exacerbation using conditional logistic regression models. RESULTS: This project has been funded by the National Health and Medical Research Council (NHMRC). The enrollment for the study has started. So far, 343 participants have been enrolled. The study is expected to be finished in October 2015. CONCLUSIONS: This study will identify risk factors for pain exacerbations in knee OA. The identification and possible modification/elimination of such risk factors will help to prevent the reoccurrence of pain exacerbation episodes and therefore improve knee OA management. PMID- 26156211 TI - Efficacy of hyperbaric oxygen therapy combined with mild hyperthermia for improving the anti-tumour effects of carboplatin. AB - PURPOSE: The aim of this study was to evaluate the effects of hyperbaric oxygen therapy (HBO) on the enhancement of hyperthermic chemosensitisation to carboplatin at mild temperatures in experimental tumours. METHODS: SCCVII carcinoma in C3H/He mice was used to assess tumour growth delay. The mice received intraperitoneal injections of carboplatin. For HBO treatment, the mice were exposed to HBO at 2.0 atmospheres of absolute oxygen for 60 min. For mild hyperthermia (HT), treatment at 41.5 degrees C for 30 min was performed. The tumour tissue pO2 levels were measured with a digital pO2 monitor during and immediately after treatment. RESULTS: The average time taken to reach a threefold relative tumour size was significantly longer after treatment with carboplatin combined with mild HT and HBO than after treatment with carboplatin and mild HT. The relative sizes of the tumours after the combined treatment were smallest when the treatment sequence was carboplatin, mild HT, and HBO. The tumour tissue pO2 values were significantly higher immediately after mild HT followed by HBO than immediately after HBO followed by mild HT. The tumour tissue pO2 levels during mild HT and HBO generally increased, although the patterns of the increases varied. CONCLUSION: The administration of HBO increased the effects of hyperthermic chemosensitisation to carboplatin at mild temperatures on experimental tumours, particularly when given in the sequence of carboplatin, mild HT, and HBO, a finding that supports previous clinical outcomes for a novel combined therapy using carboplatin plus HT and HBO. PMID- 26156212 TI - Bipolar radiofrequency ablation with 2 * 2 electrodes as a building block for matrix radiofrequency ablation: Ex vivo liver experiments and finite element method modelling. AB - PURPOSE: Size and geometry of the ablation zone obtained by currently available radiofrequency (RF) electrodes is highly variable. Reliability might be improved by matrix radiofrequency ablation (MRFA), in which the whole tumour volume is contained within a cage of x * y parallel electrodes. The aim of this study was to optimise the smallest building block for matrix radiofrequency ablation: a recently developed bipolar 2 * 2 electrode system. MATERIALS AND METHODS: In ex vivo bovine liver, the parameters of the experimental set-up were changed one by one. In a second step, a finite element method (FEM) modelling of the experiment was performed to better understand the experimental findings. RESULTS: The optimal power to obtain complete ablation in the shortest time was 50-60 W. Performing an ablation until impedance rise was superior to ablation for a fixed duration. Increasing electrode diameter improved completeness of ablation due to lower temperature along the electrodes. A chessboard pattern of electrode polarity was inferior to a row pattern due to an electric field void in between the electrodes. Variability of ablation size was limited. The FEM correctly simulated and explained the findings in ex vivo liver. CONCLUSIONS: These experiments and FEM modelling allowed a better insight in the factors influencing the ablation zone in a bipolar 2 * 2 electrode RF system. With optimal parameters, complete ablation was obtained quickly and with limited variability. This knowledge will be useful to build a larger system with x * y electrodes for MRFA. PMID- 26156214 TI - Quantum dot-layer-encapsulated and phenyl-functionalized silica spheres for highly luminous, colour rendering, and stable white light-emitting diodes. AB - Although the quantum efficiencies of quantum dots (QDs) are approaching unity through advances in the synthesis of QD materials, their luminescence efficiencies after mixing with resin and thermal curing for white light-emitting diodes (LEDs) are seriously lowered because of aggregation and oxidation of QDs and poor adhesion of QDs to the resin. To overcome these problems, QD-layer encapsulated and phenyl-functionalized silica (SQS(Ph)) spheres were synthesized and applied for white LEDs, whereby the QDs were homogeneously distributed at radial equidistance from the center and near the surface of approximately 100 nm sized silica spheres and the surface was functionalized with phenylethyl groups. The inter-core distances of QDs were over ~14 nm, which is over the limit (<10 nm) for Forster resonance energy transfer (FRET) that leads to photoluminescence (PL) reduction. This hierarchical nanostructure excludes a chance of FRET between QDs and provides the QDs a gradually refractive index matching environment, which yields ~4-fold enhanced PL in SQS(Ph). More importantly, the SQS(Ph) acquired a highly adhesive property to silicone resin due to their phenyl functional group matching, which resulted in remarkably improved light extraction in white LEDs. When incorporated along with a yellow-emitting Y3Al5O12:Ce(3+) (YAG:Ce) phosphor and silicone resin on blue LED chips, the SQS(Ph) spheres presented significantly improved performance [luminous efficiency (LE) = 58.2 lm W(-1); colour rendering index Ra = 81.8; I/I0 = 0.98 after 60 h operation] than their original QDs (LE = 39.6 lm W(-1); Ra = 78.1; I/I0 = 0.91 after 60 h operation) under a forward bias current of 60 mA. PMID- 26156213 TI - Galangin attenuates airway remodelling by inhibiting TGF-beta1-mediated ROS generation and MAPK/Akt phosphorylation in asthma. AB - Galangin, a natural flavonol, has attracted much attention for its potential anti inflammatory properties. However, its role in the regulation of airway remodelling in asthma has not been explored. The present study aimed to elucidate the effects of galangin on chronic inflammation and airway remodelling and to investigate the underlying mechanisms both in vivo and in vitro. Ovalbumin (OVA) sensitised mice were administered with galangin 30 min before challenge. Our results showed that severe inflammatory responses and airway remodelling occurred in OVA-induced mice. Treatment with galangin markedly attenuated the leakage of inflammatory cells into bronchoalveolar lavage fluid (BALF) and decreased the level of OVA-specific IgE in serum. Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and alpha-SMA expression. Lowered level of TGF beta1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo. Consistently, the TGF-beta1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway. Taken together, the present findings highlight a novel role for galangin as a promising anti-remodelling agent in asthma, which likely involves the TGF-beta1-ROS-MAPK pathway. PMID- 26156215 TI - Nutritional regulation of the anabolic fate of amino acids within the liver in mammals: concepts arising from in vivo studies. AB - At the crossroad between nutrient supply and requirements, the liver plays a central role in partitioning nitrogenous nutrients among tissues. The present review examines the utilisation of amino acids (AA) within the liver in various physiopathological states in mammals and how the fates of AA are regulated. AA uptake by the liver is generally driven by the net portal appearance of AA. This coordination is lost when demands by peripheral tissues is important (rapid growth or lactation), or when certain metabolic pathways within the liver become a priority (synthesis of acute-phase proteins). Data obtained in various species have shown that oxidation of AA and export protein synthesis usually responds to nutrient supply. Gluconeogenesis from AA is less dependent on hepatic delivery and the nature of nutrients supplied, and hormones like insulin are involved in the regulatory processes. Gluconeogenesis is regulated by nutritional factors very differently between mammals (glucose absorbed from the diet is important in single-stomached animals, while in carnivores, glucose from endogenous origin is key). The underlying mechanisms explaining how the liver adapts its AA utilisation to the body requirements are complex. The highly adaptable hepatic metabolism must be capable to deal with the various nutritional/physiological challenges that mammals have to face to maintain homeostasis. Whereas the liver responds generally to nutritional parameters in various physiological states occurring throughout life, other complex signalling pathways at systemic and tissue level (hormones, cytokines, nutrients, etc.) are involved additionally in specific physiological/nutritional states to prioritise certain metabolic pathways (pathological states or when nutritional requirements are uncovered). PMID- 26156217 TI - A Biomimic Reconstituted High-Density-Lipoprotein-Based Drug and p53 Gene Co delivery System for Effective Antiangiogenesis Therapy of Bladder Cancer. AB - A biomimic reconstituted high-density-lipoprotein-based drug and p53 gene co delivery system (rHDL/CD-PEI/p53 complexes) was fabricated as a targeted co delivery nanovector of drug and gene for potential bladder cancer therapy. Here, CD-PEI was utilized to effectively condense the p53 plasmid, to incorporate the plasmid into rHDL, and to act as an antitumor drug to suppress tumor angiogenesis. The rHDL/CD-PEI/p53 complexes exhibited desirable and homogenous particle size, neutral surface charge, and low cytotoxicity in vitro. The results of confocal laser scanning microscopy and flow cytometry confirmed that SR-BI targeted function induced specific cytoplasmic delivery and high gene transfection efficiency in MBT-2 murine bladder cells. In addition, rHDL/CD PEI/p53 complexes co-delivering CD and p53 gene achieved synergistic angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor (VEGF) messenger RNA (mRNA) and protein via different pathways in vitro. In vivo investigation on C3H/He mice bearing MBT-2 tumor xenografts revealed that rHDL/CD-PEI/p53 complexes possessed strong antitumor activity. These findings suggested that rHDL/CD-PEI/p53 complexes could be an ideal tumor-targeting system for simultaneous transfer of drug and gene, which might be a new promising strategy for effective bladder cancer therapy. PMID- 26156218 TI - 3D Hierarchical Bi2S 3 Nanostructures by Polyvinylpyrrolidone (PVP) and Chloride Ion-Assisted Synthesis and Their Photodetecting Properties. AB - A solvothermal method has been employed to synthesize bismuth sulfide (Bi2S3) with three-dimensional (3D) hierarchical architectures. The influences of different types of surfactants and Cl(-) species on the size and morphology were investigated. A possible formation mechanism was also proposed on the basis of time-dependent experiments. The photoresponse properties show that the conductivity of Bi2S3 micro-flowers is significantly enhanced and the photocurrent is approximately two orders of magnitude larger than the dark current. The response and decay times are estimated to be 142 and 151 ms, respectively. It is expected that hierarchical architectures Bi2S3 may provide a new pathway to develop advanced nanomaterial for high-speed and high-sensitivity photoelectrical switches and photodetecting devices. PMID- 26156219 TI - Effect of anti-gliadin IgY antibody on epithelial intestinal integrity and inflammatory response induced by gliadin. AB - BACKGROUND: Pepsin-trypsin resistant gliadin (PT-gliadin) promotes intestinal tissue inflammation and increases paracellular permeability of immunogenic gliadin peptides into the lamina propria. This leads to the complications seen in the pathogenesis of celiac disease (CD). In this study, specific anti-gliadin IgY antibody was produced and evaluated for its efficacy on gliadin induced intestinal integrity impairment and proinflammatory effects on intestinal epithelial (Caco-2) cell culture model for CD. METHODS: Caco-2 (passages 20-24) monolayers were subjected to 7 experimental conditions (n=3 each): phosphate buffered saline (PBS; control), pancreatic digested-casein (PD-casein; negative control), PT-gliadin (positive control), non-specific IgY with PT-gliadin, and anti-wheat gliadin IgY with PT-gliadin at a ratio of 1:6,000, 1:3,000 and 1:1,500. Caco-2 monolayers were then evaluated for effects of gliadin and/or anti wheat gliadin IgY after 24 h exposure. Enzyme-linked immunosorbent assay (ELISA) was used to quantify anti-inflammatory markers (TNF-alpha and IL-1beta) 5 days after cells were exposed to PT-gliadin and/or anti-wheat gliadin IgY. RESULTS: Among other conditions, anti-wheat gliadin IgY at a ratio of 1:3,000 (anti gliadin IgY: PT-gliadin) significantly prevented gliadin toxicity on Caco-2 by maintaining intestinal integrity, inhibiting phenol red permeation, and inhibiting gliadin absorption and production of proinflammatory cytokines (TNF alpha and IL-1beta) as compared to PT-gliadin stimulated cultures (P < 0.05). CONCLUSION: The anti-wheat gliadin IgY antibody produced in this study has proved to inhibit absorption of gliadin and gliadin-induced inflammatory response in Caco2 cell culture model of CD. Anti-gliadin IgY, therefore has potential to be used as an oral passive antibody therapy to treat CD. PMID- 26156220 TI - Biodecolorization of Reactive Yellow-2 by Serratia sp. RN34 Isolated from Textile Wastewater. AB - Remediation of colored textile wastewaters is a matter of interest. In this study, 49 bacteria were isolated from the textile wastewater and tested for their ability to decolorize reactive yellow-2 (RY2) dye. The most efficient isolate, RN34, was identified through amplification, sequencing, and phylogenetic analysis of its 16S rDNA and was designated as Serratia sp. RN34. This bacterium was also found capable of decolorizing other related reactive azo-dyes, including reactive black-5, reactive red-120, and reactive orange-16 but at varying rates. The optimum pH for decolorization of RY2 by the strain RN34 was 7.5 using yeast extract as cosubstrate under static incubation at 30 degrees C. The strain RN34 also showed potential to decolorize RY2 in the presence of considerable amounts of hexavalent chromium and sodium chloride. A phytotoxicity study demonstrated relatively reduced toxicity of RY2 decolorized products on Vigna radiata plant as compared to the uninoculated RY2 solution. PMID- 26156221 TI - MONALISA for stochastic simulations of Petri net models of biochemical systems. AB - BACKGROUND: The concept of Petri nets (PN) is widely used in systems biology and allows modeling of complex biochemical systems like metabolic systems, signal transduction pathways, and gene expression networks. In particular, PN allows the topological analysis based on structural properties, which is important and useful when quantitative (kinetic) data are incomplete or unknown. Knowing the kinetic parameters, the simulation of time evolution of such models can help to study the dynamic behavior of the underlying system. If the number of involved entities (molecules) is low, a stochastic simulation should be preferred against the classical deterministic approach of solving ordinary differential equations. The Stochastic Simulation Algorithm (SSA) is a common method for such simulations. The combination of the qualitative and semi-quantitative PN modeling and stochastic analysis techniques provides a valuable approach in the field of systems biology. RESULTS: Here, we describe the implementation of stochastic analysis in a PN environment. We extended MONALISA - an open-source software for creation, visualization and analysis of PN - by several stochastic simulation methods. The simulation module offers four simulation modes, among them the stochastic mode with constant firing rates and Gillespie's algorithm as exact and approximate versions. The simulator is operated by a user-friendly graphical interface and accepts input data such as concentrations and reaction rate constants that are common parameters in the biological context. The key features of the simulation module are visualization of simulation, interactive plotting, export of results into a text file, mathematical expressions for describing simulation parameters, and up to 500 parallel simulations of the same parameter sets. To illustrate the method we discuss a model for insulin receptor recycling as case study. CONCLUSIONS: We present a software that combines the modeling power of Petri nets with stochastic simulation of dynamic processes in a user friendly environment supported by an intuitive graphical interface. The program offers a valuable alternative to modeling, using ordinary differential equations, especially when simulating single-cell experiments with low molecule counts. The ability to use mathematical expressions provides an additional flexibility in describing the simulation parameters. The open-source distribution allows further extensions by third-party developers. The software is cross-platform and is licensed under the Artistic License 2.0. PMID- 26156216 TI - Towards microbial fermentation metabolites as markers for health benefits of prebiotics. AB - Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed. PMID- 26156222 TI - Change management in pharmacy: a simulation game and pharmacy leaders' rating of 35 barriers to change. AB - OBJECTIVES: The primary objective was to rank barriers to change in pharmacy practice. Our secondary objective was to create a simulation game to stimulate reflection and discussion on the topic of change management. METHODS: The game was created by the authors and used during a symposium attended by 43 hospital pharmacy leaders from all regions of Canada (Millcroft Conference, Alton, Ontario, June 2013). The main theme of the conference was 'managing change'. KEY FINDINGS: The simulation game, the rating of 35 barriers to change and the discussion that followed provided an opportunity for hospital pharmacy leaders to reflect on potential barriers to change, and how change might be facilitated through the use of an organized approach to change, such as that described in Kotter's eight-step model. CONCLUSIONS: This simulation game, and the associated rating of barriers to change, provided an opportunity for a group of hospital pharmacy leaders in Canada to reflect on the challenges associated with managing change in the healthcare setting. This simulation game can be modified and used by pharmacy practitioners in other countries to help identify and rank barriers to change in their particular pharmacy practice setting. PMID- 26156224 TI - BBC is accused of bias in charging Indian government with suppressing report on child malnutrition. PMID- 26156225 TI - A modified Austin/chevron osteotomy for treatment of hallux valgus and hallux rigidus. AB - The purpose of this brief paper is to present the preliminary results of a modified Austin/chevron osteotomy for treatment of hallux valgus and hallux rigidus. In this procedure, the dorsal arm of the osteotomy is performed orthogonal to the horizontal plane of the first metatarsal, the main advantage being that this allows much easier and more accurate multiplanar correction of first metatarsal deformities. From 2010 to 2013, 184 consecutive patients with symptomatic hallux valgus and 48 patients with hallux rigidus without severe metatarsophalangeal joint degeneration underwent such modified chevron osteotomy. Mean patient age was 54.9 (range 21-70) years, and mean follow-up duration was 41.7 (range 24-56) months. Ninety-three percent of patients were satisfied with the surgery. Mean American Orthopaedic Foot and Ankle Society (AOFAS) score improved from 56.6 preoperatively to 90.6 at last follow-up, and mean visual analog scale (VAS) pain score decreased from 5.7 preoperatively to 1.6 at final follow-up (p < 0.05). In patients treated for hallux valgus, mean hallux valgus angle decreased from 34.1 degrees preoperatively to 6.2 degrees at final follow up, and mean intermetatarsal angle decreased from 18.5 degrees preoperatively to 4.1 degrees at final follow-up (p < 0.05). One patient developed postoperative transfer metatarsalgia, treated successfully with second-time percutaneous osteotomy of the minor metatarsals, whilst one patient had wound infection that resolved with systemic antibiotics. LEVEL OF EVIDENCE: Level IV. PMID- 26156223 TI - The Genetic Basis of Composite Spike Form in Barley and 'Miracle-Wheat'. AB - Inflorescences of the tribe Triticeae, which includes wheat (Triticum sp. L.) and barley (Hordeum vulgare L.) are characterized by sessile spikelets directly borne on the main axis, thus forming a branchless spike. 'Compositum-Barley' and tetraploid 'Miracle-Wheat' (T. turgidum convar. compositum (L.f.) Filat.) display noncanonical spike-branching in which spikelets are replaced by lateral branch like structures resembling small-sized secondary spikes. As a result of this branch formation 'Miracle-Wheat' produces significantly more grains per spike, leading to higher spike yield. In this study, we first isolated the gene underlying spike-branching in 'Compositum-Barley,' i.e., compositum 2 (com2). Moreover, we found that COM2 is orthologous to the branched head(t) (bh(t)) locus regulating spike branching in tetraploid 'Miracle-Wheat.' Both genes possess orthologs with similar functions in maize BRANCHED SILKLESS 1 (BD1) and rice FRIZZY PANICLE/BRANCHED FLORETLESS 1 (FZP/BFL1) encoding AP2/ERF transcription factors. Sequence analysis of the bh(t) locus in a collection of mutant and wild type tetraploid wheat accessions revealed that a single amino acid substitution in the DNA-binding domain gave rise to the domestication of 'Miracle-Wheat.' mRNA in situ hybridization, microarray experiments, and independent qRT-PCR validation analyses revealed that the branch repression pathway in barley is governed through the spike architecture gene Six-rowed spike 4 regulating COM2 expression, while HvIDS1 (barley ortholog of maize INDETERMINATE SPIKELET 1) is a putative downstream target of COM2. These findings presented here provide new insights into the genetic basis of spike architecture in Triticeae, and have disclosed new targets for genetic manipulations aiming at boosting wheat's yield potential. PMID- 26156226 TI - A pilot study about speech changes after partial Tucker's laryngectomy: the reduction of regressive voicing assimilation. AB - Partial frontolateral laryngectomy (PL) is performed to remove larynx tumor while preserving its main functions. So far, the speech changes induced by difficulties of voicing and the alterations to the vocal tract due to PL have been seldom addressed. The goal of our study was to make an acoustic analysis of regressive voicing assimilation (RVA) among patients after PL and to study the relationship with rates of speech. A retrospective study was conducted from January to April 2013. 11 subjects treated by partial frontolateral laryngectomy, and ten healthy subjects were included. Functional recordings of voice were analyzed and compared. For assimilation sequences we found a significant modification of voicing ratio in healthy subjects (p < 0.05) and PL patient at accelerated speaking rate only (p < 0.05). The vowel duration is significantly modified only for healthy subjects. For all subjects (PL patients and healthy) the duration of C1 consonant was not significantly modified. Our results highlight the presence of RVA in healthy subjects, but also in PL patients in the rapid speaking mode. PMID- 26156227 TI - The impact of tissue glue in wound healing of head and neck patients undergoing neck dissection. AB - We investigated the impact of fibrin glue on postoperative drainage amount and duration in head and neck cancer patients who underwent neck dissection. This study was a prospective randomized controlled trial. Patients who were scheduled to undergo neck dissection due to head and neck cancer were eligible for this study. After receiving a detailed explanation, all patients signed an informed consent form before enrollment. Patients were then randomly assigned to the study group (fibrin glue) or control group. In the study group, 2 ml of fibrin glue (Tissucol((r)); Duploject, Baxter AG) was applied on the surface of the surgical wound before closure. Basic demographic data along with tumor-related features, operation-related variables, postoperative drainage amount/duration, postoperative pain, and analgesic usage were collected and analyzed. A total of 15 patients were included in the final analyses, with eight patients in the study group and seven patients in the control group. No significant differences were found between the two groups in age, gender, primary site, clinical N stage, neck dissection levels, perioperative bleeding, postoperative drainage amount/duration, hospitalization duration, and postoperative pain status. The application of 2 ml fibrin glue by the method described herein did not reduce the postoperative drainage amount/duration nor the postoperative pain status in patients who underwent neck dissection. PMID- 26156228 TI - Cognitive and psychological flexibility after a traumatic brain injury and the implications for treatment in acceptance-based therapies: A conceptual review. AB - This paper provides a selective review of cognitive and psychological flexibility in the context of treatment for psychological distress after traumatic brain injury, with a focus on acceptance-based therapies. Cognitive flexibility is a component of executive function that is referred to mostly in the context of neuropsychological research and practice. Psychological flexibility, from a clinical psychology perspective, is linked to health and well-being and is an identified treatment outcome for therapies such as acceptance and commitment therapy (ACT). There are a number of overlaps between the constructs. They both manifest in the ability to change behaviour (either a thought or an action) in response to environmental change, with similarities in neural substrate and mental processes. Impairments in both show a strong association with psychopathology. People with a traumatic brain injury (TBI) often suffer impairments in their cognitive flexibility as a result of damage to areas controlling executive processes but have a positive response to therapies that promote psychological flexibility. Overall, psychological flexibility appears a more overarching construct and cognitive flexibility may be a subcomponent of it but not necessarily a pre-requisite. Further research into therapies which claim to improve psychological flexibility, such as ACT, needs to be undertaken in TBI populations in order to clarify its utility in this group. PMID- 26156230 TI - Energy allocation during the maturation of adults in a long-lived insect: implications for dispersal and reproduction. AB - Energy allocation strategies have been widely documented in insects and were formalized in the context of the reproduction process by the terms 'capital breeder' and 'income breeder'. We propose here the extension of this framework to dispersal ability, with the concepts of 'capital disperser' and 'income disperser', and explore the trade-off in resource allocation between dispersal and reproduction. We hypothesized that flight capacity was sex-dependent, due to a trade-off in energy allocation between dispersal and egg production in females. We used Monochamus galloprovincialis as model organism, a long-lived beetle which is the European vector of the pine wood nematode. We estimated the flight capacity with a flight mill and used the number of mature eggs as a proxy for the investment in reproduction. We used the ratio between dry weights of the thorax and the abdomen to investigate the trade-off. The probability of flying increased with the adult weight at emergence, but was not dependent on insect age or sex. Flight distance increased with age in individuals but did not differ between sexes. It was also positively associated with energy allocation to thorax reserves, which increased with age. In females, the abdomen weight and the number of eggs also increase with age with no negative effect on flight capacity, indicating a lack of trade-off. This long-lived beetle has a complex strategy of energy allocation, being a 'capital disperser' in terms of flight ability, an 'income disperser' in terms of flight performance and an 'income breeder' in terms of egg production. PMID- 26156229 TI - The combination of intravenous Reolysin and gemcitabine induces reovirus replication and endoplasmic reticular stress in a patient with KRAS-activated pancreatic cancer. AB - BACKGROUND: Activating mutations in RAS are present in the majority of pancreatic cancer cases and represent an ideal therapeutic target. Reolysin is a proprietary formulation of oncolytic reovirus that is currently being evaluated in multiple clinical trials due to its ability to selectively replicate in cells harboring an activated RAS pathway. Here we report for the first time the presence of reovirus replication and induction of endoplasmic reticular (ER) stress in a primary tumor specimen collected from a pancreatic cancer patient receiving intravenous Reolysin and gemcitabine. CASE PRESENTATION: We describe the case of a 54-year old patient diagnosed with pancreatic adenocarcinoma in February 2012. Analysis of a tumor biopsy revealed an activating KRAS mutation (G12D) and the patient was started on first-line treatment with Reolysin in combination with gemcitabine in March 2012. Stable disease was achieved with significant improvement in cancer related pain. Following 25 cycles of treatment over 23 months, a second biopsy was collected and immunohistochemical analyses revealed the presence of reovirus replication and induction of the ER stress-related gene GRP78/BIP and the pro apoptotic protein NOXA. Importantly, co-localization of reoviral protein and active caspase-3 was also observed in the biopsy specimen. CONCLUSION: This is the first report of reoviral protein detection in primary tumor biopsies taken from a pancreatic cancer patient receiving intravenous Reolysin therapy. The accumulation of reoviral protein was associated with ER stress induction and caspase-3 processing suggesting that Reolysin and gemcitabine treatment exhibited direct pro-apoptotic activity against the tumor. PMID- 26156231 TI - Dynamic CT perfusion measurement in a cardiac phantom. AB - Widespread clinical implementation of dynamic CT myocardial perfusion has been hampered by its limited accuracy and high radiation dose. The purpose of this study was to evaluate the accuracy and radiation dose reduction of a dynamic CT myocardial perfusion technique based on first pass analysis (FPA). To test the FPA technique, a pulsatile pump was used to generate known perfusion rates in a range of 0.96-2.49 mL/min/g. All the known perfusion rates were determined using an ultrasonic flow probe and the known mass of the perfusion volume. FPA and maximum slope model (MSM) perfusion rates were measured using volume scans acquired from a 320-slice CT scanner, and then compared to the known perfusion rates. The measured perfusion using FPA (P(FPA)), with two volume scans, and the maximum slope model (P(MSM)) were related to known perfusion (P(K)) by P(FPA) = 0.91P(K) + 0.06 (r = 0.98) and P(MSM) = 0.25P(K) - 0.02 (r = 0.96), respectively. The standard error of estimate for the FPA technique, using two volume scans, and the MSM was 0.14 and 0.30 mL/min/g, respectively. The estimated radiation dose required for the FPA technique with two volume scans and the MSM was 2.6 and 11.7 17.5 mSv, respectively. Therefore, the FPA technique can yield accurate perfusion measurements using as few as two volume scans, corresponding to approximately a factor of four reductions in radiation dose as compared with the currently available MSM. In conclusion, the results of the study indicate that the FPA technique can make accurate dynamic CT perfusion measurements over a range of clinically relevant perfusion rates, while substantially reducing radiation dose, as compared to currently available dynamic CT perfusion techniques. PMID- 26156233 TI - Differentiated tonsil-derived mesenchymal stem cells embedded in Matrigel restore parathyroid cell functions in rats with parathyroidectomy. AB - Parathyroid cells release parathyroid hormone (PTH), which controls calcium homeostasis. Loss of parathyroid cells results in hypoparathyroidism and consequent low-turnover bone disease. Here, we investigated whether our recently established human tonsil-derived mesenchymal stem cells (TMSC) restore in vivo parathyroid cell function in rats with parathyroidectomy (PTX). Compared with undifferentiated control TMSC, TMSC differentiated with activin A and soluble sonic hedgehog induced a significant release of PTH as early as day 7, with increased PTH release occurring in response to lower calcium levels and vice versa. Released PTH increased osteocalcin expression and alizarin red S staining in preosteoblastic cells, indicating its functional activity. PTX rats fed calcium-free diet only survived for ~10 days. Subcutaneous injection with TMSC alone did not increase their survival rates, regardless of differentiation. However, survival rates increased for up to 28 days in response to TMSC embedded in Matrigel (TMSC-MA), showing 40% and 80% in control and differentiated TMSC-MA, respectively. When compared with continuous increases by control TMSC-MA, stable levels of secreted PTH and serum ionized calcium were found in PTX rats with differentiated TMSC-MA. This is the first report that differentiated TMSC resemble parathyroid cells and, if embedded in Matrigel, restore in vivo parathyroid function. PMID- 26156232 TI - Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II-Induced Hypertension. AB - RATIONALE: Inflammation and adaptive immunity play a crucial role in the development of hypertension. Angiotensin II and probably other hypertensive stimuli activate the central nervous system and promote T-cell activation and end organ damage in peripheral tissues. OBJECTIVE: To determine if renal sympathetic nerves mediate renal inflammation and T-cell activation in hypertension. METHODS AND RESULTS: Bilateral renal denervation using phenol application to the renal arteries reduced renal norepinephrine levels and blunted angiotensin II-induced hypertension. Bilateral renal denervation also reduced inflammation, as reflected by decreased accumulation of total leukocytes, T cells, and both CD4+ and CD8+ T cells in the kidney. This was associated with a marked reduction in renal fibrosis, albuminuria, and nephrinuria. Unilateral renal denervation, which partly attenuated blood pressure, only reduced inflammation in the denervated kidney, suggesting that this effect is pressure independent. Angiotensin II also increased immunogenic isoketal-protein adducts in renal dendritic cells (DCs) and increased surface expression of costimulation markers and production of interleukin (IL)-1alpha, IL-1beta, and IL-6 from splenic DCs. Norepinephrine also dose dependently stimulated isoketal formation in cultured DCs. Adoptive transfer of splenic DCs from angiotensin II-treated mice primed T-cell activation and hypertension in recipient mice. Renal denervation prevented these effects of hypertension on DCs. In contrast to these beneficial effects of ablating all renal nerves, renal afferent disruption with capsaicin had no effect on blood pressure or renal inflammation. CONCLUSIONS: Renal sympathetic nerves contribute to DC activation, subsequent T-cell infiltration and end-organ damage in the kidney in the development of hypertension. PMID- 26156234 TI - Factors influencing the career choice and retention of community mental health workers in Ghana. AB - BACKGROUND: Whilst there have been several studies exploring retention in health workers, little is known about health workers engaged in the provision of mental health services and the factors that affect their recruitment and retention. AIMS: The objective of this research was to examine the views of stakeholders about the factors which influence career choices and retention of community mental health workers (CMHWs) in Ghana. METHODS: We administered three separate, self-administered, semi-structured questionnaires to 11 psychiatrists, 29 health policy directors and 164 CMHWs across Ghana, including 71 (43.3%) community psychiatric nurses (CPNs), 19 (11.6%) clinical psychiatric officers (CPOs) and 74 (45.1%) community mental health officers (CMHOs). RESULTS: Overall, 34 (20.7%) of all CMHWs chose to work in mental health because of the job prospects in mental healthcare. Overall, 12 (16.2%) CMHOs, 1 (5.3%) CPO and 20 (28.2%) CPNs reported they had considered leaving the mental health profession because of the stigma, with 4 (36.4%) psychiatrists and 12 (41.4%) health policy coordinators also reporting that they knew some CMHWs who had considered leaving the mental health profession because of stigma. Similarly, 16 (21.6%) CMHOs, 4 (22.1%) CPOs and 38 (53.5%) CPNs said they had considered leaving the mental health profession because of concerns about risk. Furthermore, 6 (54.5%) psychiatrists and 3 (10.3%) health policy directors said they knew some CMHWs who had considered leaving the mental health profession because of concerns about risk. Overall, 61 (37.2%) of CMHWs reported that they have considered leaving the mental health profession for other reasons other than stigma and risk including the following: the lack of support, respect and recognition from healthcare managers, lack of opportunities for professional development and poor conditions of service including low salaries, lack of office and personal accommodation and lack of risk allowance and transportation as well as poor inter-professional relationships. CONCLUSIONS: Several factors affect the recruitment and retention of CMHWs in Ghana, including the prospects of easy employment, stigma, risk, lack of opportunities for career progression and low salaries. PMID- 26156235 TI - Genetic variants influencing response to methotrexate in juvenile idiopathic arthritis and rheumatoid arthritis. PMID- 26156236 TI - Visual attention shifting in autism spectrum disorders. AB - INTRODUCTION: Abnormal visual attention has been frequently observed in autism spectrum disorders (ASD). Abnormal shifting of visual attention is related to abnormal development of social cognition and has been identified as a key neuropsychological finding in ASD. Better characterizing attention shifting in ASD and its relationship with social functioning may help to identify new targets for intervention and improving social communication in these disorders. Thus, the current study investigated deficits in attention shifting in ASD as well as relationships between attention shifting and social communication in ASD and neurotypicals (NT). METHOD: To investigate deficits in visual attention shifting in ASD, 20 ASD and 20 age- and gender-matched NT completed visual search (VS) and Navon tasks with attention-shifting demands as well as a set-shifting task. VS was a feature search task with targets defined in one of two dimensions; Navon required identification of a target letter presented at the global or local level. Psychomotor and processing speed were entered as covariates. Relationships between visual attention shifting, set shifting, and social functioning were also examined. RESULTS: ASD and NT showed comparable costs of shifting attention. However, psychomotor and processing speed were slower in ASD than in NT, and psychomotor and processing speed were positively correlated with attention shifting costs on Navon and VS, respectively, for both groups. Attention shifting on VS and Navon were correlated among NT, while attention shifting on Navon was correlated with set shifting among ASD. Attention-shifting costs on Navon were positively correlated with restricted and repetitive behaviors among ASD. CONCLUSIONS: Relationships between attention shifting and psychomotor and processing speed, as well as relationships between measures of different aspects of visual attention shifting, suggest inefficient top-down influences over preattentive visual processing in ASD. Inefficient attention shifting may be related to restricted and repetitive behaviors in these disorders. PMID- 26156238 TI - Recombinant Trichoderma harzianum endoglucanase I (Cel7B) is a highly acidic and promiscuous carbohydrate-active enzyme. AB - Trichoderma filamentous fungi have been investigated due to their ability to secrete cellulases which find various biotechnological applications such as biomass hydrolysis and cellulosic ethanol production. Previous studies demonstrated that Trichoderma harzianum IOC-3844 has a high degree of cellulolytic activity and potential for biomass hydrolysis. However, enzymatic, biochemical, and structural studies of cellulases from T. harzianum are scarce. This work reports biochemical characterization of the recombinant endoglucanase I from T. harzianum, ThCel7B, and its catalytic core domain. The constructs display optimum activity at 55 degrees C and a surprisingly acidic pH optimum of 3.0. The full-length enzyme is able to hydrolyze a variety of substrates, with high specific activity: 75 U/mg for beta-glucan, 46 U/mg toward xyloglucan, 39 U/mg for lichenan, 26 U/mg for carboxymethyl cellulose, 18 U/mg for 4-nitrophenyl beta D-cellobioside, 16 U/mg for rye arabinoxylan, and 12 U/mg toward xylan. The enzyme also hydrolyzed filter paper, phosphoric acid swollen cellulose, Sigmacell 20, Avicel PH-101, and cellulose, albeit with lower efficiency. The ThCel7B catalytic domain displays similar substrate diversity. Fluorescence-based thermal shift assays showed that thermal stability is highest at pH 5.0. We determined kinetic parameters and analyzed a pattern of oligosaccharide substrates hydrolysis, revealing cellobiose as a final product of C6 degradation. Finally, we visualized effects of ThCel7B on oat spelt using scanning electron microscopy, demonstrating the morphological changes of the substrate during the hydrolysis. The acidic behavior of ThCel7B and its considerable thermostability hold a promise of its industrial applications and other biotechnological uses under extremely acidic conditions. PMID- 26156237 TI - The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines. AB - Herceptin is considered an essential treatment option for double negative breast cancer. Resveratrol and didox are known chemopreventive agents with potential anticancer properties. The aim of the current study is to investigate the influence of resveratrol and didox on the cytotoxicity profile of herceptin in HER-2 receptor positive and HER-2 receptor negative breast cancer cell lines (T47D and MCF-7 cell lines, respectively). The IC50's of herceptin in T47D and MCF-7 were 0.133 +/- 0.005 ng/ml and 23.3795 +/- 1.99 ng/ml respectively. Equitoxic combination of herceptin with resveratrol or didox in T47D significantly reduced the IC50 to 0.052 +/- 0.001 and 0.0365 +/- 0.001 ng/ml, respectively and similar results were obtained in MCF-7. The gene expression of BCL-xl was markedly decreased in T47D cells following treatment with herceptin/resveratrol compared to herceptin alone. Immunocytochemical staining of HER-2 receptor in T47D cells showed a significant reduction after treatment with herceptin/resveratrol combination compared to herceptin alone. On the contrary, herceptin/didox combination had no significant effect on HER-2 receptor expression. Cell cycle analysis showed an arrest at G2/M phase for both cell lines following all treatments. In conclusion, herceptin/resveratrol and herceptin/didox combinations improved the cytotoxic profile of herceptin in both T47D and MCF-7 breast cancer cell lines. PMID- 26156239 TI - Spatiotemporal dynamics and determinants of planktonic bacterial and microeukaryotic communities in a Chinese subtropical river. AB - The spatiotemporal distribution of microbial diversity, community composition, and their major drivers are fundamental issues in microbial ecology. In this study, the planktonic bacterial and microeukaryotic communities of the Jiulong River were investigated across both wet and dry seasons by using denaturing gradient gel electrophoresis (DGGE). We found evidence of temporal change between wet and dry seasons and distinct spatial patterns of bacterial and microeukaryotic communities. Both bacterial and microeukaryotic communities were strongly correlated with temperature, NH4-N, PO4-P, and chlorophyll a, and these environmental factors were significant but incomplete predictors of microbial community composition. Local environmental factors combined with spatial and temporal factors strongly controlled both bacterial and microeukaryotic communities in complex ways, whereas the direct influence of spatial and temporal factors appeared to be relatively small. Path analysis revealed that the microeukaryotic community played key roles in shaping bacterial community composition, perhaps through grazing effects and multiple interactions. Both Betaproteobacteria and Actinobacteria were the most dominant and diverse taxa in bacterial communities, while the microeukaryotic communities were dominated by Ciliophora (zooplankton) and Chlorophyta (phytoplankton). Our results demonstrated that both bacterial and microeukaryotic communities along the Jiulong River displayed a distinct spatiotemporal pattern; however, microeukaryotic communities exhibited a stronger distance-decay relationship than bacterial communities and their spatial patterns were mostly driven by local environmental variables rather than season or spatial processes of the river. Therefore, we have provided baseline data to support further research on river microbial food webs and integrating different microbial groups into river models. PMID- 26156240 TI - Novel extracellular medium-chain-length polyhydroxyalkanoate depolymerase from Streptomyces exfoliatus K10 DSMZ 41693: a promising biocatalyst for the efficient degradation of natural and functionalized mcl-PHAs. AB - Cloning and biochemical characterization of a novel extracellular medium-chain length polyhydroxyalkanoate (mcl-PHA) depolymerase from Streptomyces exfoliatus K10 DSMZ 41693 are described. The primary structure of the depolymerase (PhaZSex2) includes the lipase consensus sequence (serine-histidine-aspartic acid) which is known for serine hydrolases. Secondary structure analysis shows 7.9 % alpha-helix, 43.9 % beta-sheet, 19.4 % beta-turns, and 31.2 % random coil, suggesting that this enzyme belongs to the alpha/beta hydrolase fold family, in agreement with other PHA depolymerases and lipases. The enzyme was efficiently produced as an extracellular active form in Rhodococcus and purified by two consecutive hydrophobic chromatographic steps. Matrix-assisted laser desorption time-of-flight (MALDI-TOF) analysis of the purified enzyme revealed a monomer of 27.6 kDa with a midpoint transition temperature of 44.2 degrees C. Remarkably, the activity is significantly enhanced by low concentrations of nonionic and anionic detergents and thermal stability is improved by the presence of 10 % glycerol. PhaZSex2 is an endo-exohydrolase that cleaves both large and small PHA molecules, producing (R)-3-hydroxyoctanoic acid monomers as the main reaction product. Markedly, PhaZSex2 is able to degrade functionalized polymers containing thioester groups in the side chain (PHACOS), releasing functional thioester-based monomers and oligomers demonstrating the potentiality of this novel biocatalyst for the industrial production of enantiopure (R)-3-hydroxyalkanoic acids. PMID- 26156241 TI - Highly efficient biosynthesis of astaxanthin in Saccharomyces cerevisiae by integration and tuning of algal crtZ and bkt. AB - Astaxanthin is a highly valued carotenoid with strong antioxidant activity and has wide applications in aquaculture, food, cosmetic, and pharmaceutical industries. The market demand for natural astaxanthin promotes research in metabolic engineering of heterologous hosts for astaxanthin production. In this study, an astaxanthin-producing Saccharomyces cerevisiae strain was created by successively introducing the Haematococcus pluvialis beta-carotenoid hydroxylase (crtZ) and ketolase (bkt) genes into a previously constructed beta-carotene hyperproducer. Further integration of strategies including codon optimization, gene copy number adjustment, and iron cofactor supplementation led to significant increase in the astaxanthin production, reaching up to 4.7 mg/g DCW in the shake flask cultures which is the highest astaxanthin content in S. cerevisiae reported to date. Besides, the substrate specificity of H. pluvialis CrtZ and BKT and the probable formation route of astaxanthin from beta-carotene in S. cerevisiae were figured out by expressing the genes separately and in combination. The yeast strains engineered in this work provide a basis for further improving biotechnological production of astaxanthin and might offer a useful general approach to the construction of heterologous biosynthetic pathways for other natural products. PMID- 26156242 TI - Establishment and characterization of a telomerase-immortalized canine bronchiolar epithelial cell line. AB - Dogs are susceptible to infectious diseases that occur primarily in the respiratory tract. The airway epithelium acts as a first line of defense and is constantly exposed to microorganisms present in the environment. Respiratory epithelial cells have recently gained wide use as a cell model for studying the pathogenesis of human, murine or swine respiratory pathogen infections. However, studies of the pathogenic mechanisms of canine pathogens have been hindered by the lack of reliable respiratory cell lines. Here, we cultured primary canine bronchiolar epithelial cells (CBECs), whose characteristics were confirmed by their expression of the epithelial cell-specific marker cytokeratin 18, and have provided protocols for their isolation and ex vivo expansion. Further, we established immortalized CBECs containing the human telomerase reverse transcriptase (hTERT) gene via transfection of primary CBECs with the recombinant plasmid pEGFP-hTERT. Immortalized bronchiolar epithelial cells (hTERT-CBECs) retain the morphological and functional features of primary CBECs, as indicated by reverse transcriptase polymerase chain reaction, proliferation assays, karyotype analysis, telomerase activity assay, and Western blotting, which demonstrate that hTERT-CBECs have higher telomerase activity, an extended proliferative lifespan, and a diploid complement of chromosomes, even after Passage 50. Moreover, this cell line is not transformed, as evaluated using soft agar assays and tumorigenicity analysis in nude mice, and can therefore be safely used in future studies. The isolation and establishment of stable hTERT-CBECs is of great importance for use as an in vitro model for mechanistic studies of canine pathogenic infections. PMID- 26156243 TI - The phylogenetic relationships of endemic Australasian trichostrongylin families (Nematoda: Strongylida) parasitic in marsupials and monotremes. AB - The phylogenetic relationships of the endemic (or largely endemic) Australasian trichostrongylin nematode families Herpetostrongylidae, Mackerrastrongylidae and Nicollinidae as well as endemic trichostrongylin nematodes currently placed in the families Trichostrongylidae and Molineidae were examined using the complete large subunit (28S) ribosomal RNA gene. The Herpetostrongylinae proved to be monophyletic. However, representatives of the Nicollinidae nested with the Herpetostrongylinae. The Mackerrastrongylidae was also a monophyletic group and included Peramelistrongylus, currently classified within the Trichostrongylidae. The Globocephaloidinae, currently considered to be a subfamily of the Herpetostrongylidae, was excluded from the family in the current analysis. Ollulanus and Libyostrongylus, included for the first time in a molecular phylogenetic analysis, were placed within the Trichostrongylidae. This study provided strong support for the Herpetostrongylidae (including within it the Nicollinidae, but excluding the Globocephaloidinae) and the Mackerrastrongylidae as monophyletic assemblages. Additional studies are required to resolve the relationships of the remaining endemic Australasian trichostrongylin genera. PMID- 26156244 TI - Respiratory Syncytial Virus Utilizes a tRNA Fragment to Suppress Antiviral Responses Through a Novel Targeting Mechanism. AB - Target identification is highly instructive in defining the biological roles of microRNAs. However, little is known about other small noncoding RNAs; for example, tRNA-derived RNA Fragments (tRFs). Some tRFs exhibit a gene-silencing mechanism distinctly different from that of typical microRNAs. We recently demonstrated that a respiratory syncytial virus (RSV)-induced tRF, called tRF5 GluCTC, promotes RSV replication. RSV is the single most important cause of lower respiratory tract infection in children. By using biochemical screening and bioinformatics analyses, we have identified apolipoprotein E receptor 2 (APOER2) as a target of tRF5-GluCTC. The 3'-portion of tRF5-GluCTC recognizes a target site in the 3'-untranslated region of APOER2 and suppresses its expression. We have also discovered that APOER2 is an anti-RSV protein whose suppression by tRF5 GluCTC promotes RSV replication. Our report represents the first identification of a natural target of a tRF and illustrates how a virus utilizes a host tRF to control a host gene to favor its replication. PMID- 26156247 TI - Comparison studies of rheological and thermal behaviors of ionic liquids and nanoparticle ionic liquids. AB - Novel nanoparticle ionic liquids (NILs) are prepared by grafting modified nanoparticles with long-chain ionic liquids (ILs). The NIL behaves like a liquid at ambient temperature. We studied the rheological behavior of the IL and NIL over the range of 10-55 degrees C and found an extraordinary difference between the IL and NIL: a small content of nanosilica (7%) moderately improves the crystallinity by 7% of the poly(ethylene glycol) (PEG) segment in the IL, and it improves the dynamic moduli significantly (by 5 times at room temperature). It retards the decay temperature (by 10 degrees C) of the dynamic moduli during heating as well. The thermal rheological hysteresis observed during heating cooling temperature sweeps is ascribed to the melting-recrystallization of the PEG segments. Meanwhile, the IL and NIL express accelerated crystallization behavior in comparison with the oligomeric anion. For the first time, we find that ILs and NILs are able to form nanoparticle-containing spherulites at room temperature after long time aging. PMID- 26156246 TI - Mortality among drowning rescuers in China, 2013: a review of 225 rescue incidents from the press. AB - BACKGROUND: Drowning is common worldwide. Rescue efforts attempted by untrained bystanders often lead to the death of the primary drowning victim (PDV), the rescuer or both. Our study aimed to inform prevention by identifying risk factors in rescuer drowning. METHODS: Data on drowning rescue incidents reported online in mainland China, 2013, were reviewed. Information on the drowning incidents, PDVs and rescuers were retrieved for analysis. RESULTS: A total of 225 rescue incidents were identified, of which 14 were victim-rescuer drowning incidents (VRDIs) (6.2%). A person-to-person rescue by swimming to PDVs was the most commonly used method (58.9%). Resuscitation was given immediately to 35.5% of PDVs after rescue. The mortality rate of the rescuers (13.3%) was similar to that of the PDVs (11.5%) (chi(2) = 0.5, p =0.49). Being an adult (OR = 0.2, 95% CI: 0.1-0.5) and other than the first rescuer (OR = 0.4, 95% CI: 0.2-0.9) decreased the risk of rescuers drowning. CONCLUSIONS: Most of the currently employed life saving methods are dangerous and even potentially life threatening. The idea of "rescuers' safety first" should be embraced, especially with teenage and child rescuers, who should never be encouraged to rescue others without first guaranteeing their own safety. Promotion of basic rescue skills should be implemented in the general public. PMID- 26156245 TI - Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues. AB - In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients. PMID- 26156248 TI - Virtual colonoscopy, optical colonoscopy, or fecal occult blood testing for colorectal cancer screening: results of a pilot randomized controlled trial. AB - BACKGROUND: No head-to-head randomized controlled trials have demonstrated the superiority of one colorectal screening modality over another in reducing colorectal cancer mortality. We conducted a pilot randomized controlled trial of fecal occult blood testing (FOBT), optical colonoscopy (OC), and virtual colonoscopy (VC), to inform the planning of a larger evaluative trial. METHODS: Eligible patients (aged 50 to 70) were recruited from five primary care practices in Hamilton, ON, Canada, between March 23, 2010 and August 11, 2010, and randomized 1:1:1 in a parallel design using an automated, centralized telephone service to either FOBT, OC, or VC. To reflect conventional practice, patients received no additional reminders to complete their allocated screening test beyond those received in usual practice. The primary outcome was completion of the assigned screening procedure. Results of the index test and any follow-up investigations were ascertained at 6 months. Participants, caregivers, and outcome assessors were not blinded to group assignment. The trial was stopped early due to lack of ongoing funding. RESULTS: A total of 198 participants were enrolled, of whom 67 were allocated to FOBT, 66 to OC, and 65 to VC. The allocated screening procedure was completed by 43 (64%) subjects allocated to FOBT (95% confidence interval [CI], 52-75%), 53 (80%) subjects allocated to OC (95% CI, 69-88%), and 50 (77%) subjects allocated to VC (95% CI, 65-85%); because the trial stopped early, we had insufficient statistical power to detect clinically relevant differences in completion rates. During 6 months follow-up, colorectal adenomas were detected in 0 (0%) subjects allocated to FOBT, 12 (18%) subjects allocated to OC, and 2 (3%) subjects allocated to VC. One subject in the OC arm had histological evidence of high-grade dysplasia. No subjects were diagnosed with colorectal cancer. CONCLUSIONS: In this pilot randomized controlled trial of colorectal cancer screening in a primary care setting, 64-80% of subjects completed their allocated screening test. These findings may be of value to investigators planning clinical trials to evaluate the effectiveness of colorectal cancer screening. TRIAL REGISTRATION: ClinicalTrials.gov NCT00865527. https://clinicaltrials.gov/ct2/show/NCT00865527. PMID- 26156249 TI - Three linked nomograms for predicting biochemical failure in prostate cancer treated with radiotherapy plus androgen deprivation therapy. AB - BACKGROUND: Nomograms were established to predict biochemical recurrence (BCR) after radiotherapy (RT) with a low weight of the characteristic variables of RT and androgen deprivation therapy (ADT). Our aim is to provide a new stratified tool for predicting BCR at 4 and 7 years in patients treated using RT with radical intent. MATERIALS AND METHODS: A retrospective, nonrandomized analysis was performed on 5044 prostate cancer (PCa) patients with median age 70 years, who received RT-with or without ADT-between November 1992 and May 2007. Median follow-up was 5.5 years. BCR was defined as a rise in serum prostate-specific antigen (PSA) of 2 ng/ml over the post-treatment PSA nadir. Univariate association between predictor variables and BCR was assessed by the log-rank test, and three linked nomograms were created for multivariate prognosis of BCR free survival. Each nomogram corresponds to a category of the Gleason score either 6,7, or 8-10-and all of them were created from a single proportional hazards regression model stratified also by months of ADT (0, 1-6, 7-12, 13-24, 25-36, 36-60). The performance of this model was analyzed by calibration, discrimination, and clinical utility. RESULTS: Initial PSA, clinical stage, and RT dose were significant variables (p < 0.01). The model showed a good calibration. The concordance probability was 0.779, improving those obtained with other nomograms (0.587, 0.571, 0.554) in the database. Survival curves showed best clinical utility in a comparison with National Comprehensive Cancer Network (NCCN) risk groups. CONCLUSION: For each Gleason score category, the nomogram provides information on the benefit of adding ADT to a specific RT dose. PMID- 26156250 TI - Accuracy of high-density genotype imputation in Japanese Black cattle. AB - Genotype imputation facilitates the identification of missing genotypes on a high density array using low-density arrays and has great potential for reducing genotyping costs for cattle populations. However, the imputation quality varies across breeds, which have different effective population sizes. Therefore, the accuracy of genotype imputation must be evaluated in each breed. The Japanese Black cattle population has a unique genetic background, and this study aimed to investigate different factors affecting imputation quality in this population. A total of 1368 animals were genotyped using the Illumina BovineHD BeadChip, and the accuracy of imputation was evaluated using information from four lower density arrays. The extent of linkage disequilibrium for this population was relatively higher than that in other beef breeds but lower than that in dairy breeds. The accuracy of arrays with more than 20 000 single nucleotide polymorphisms (SNPs) was similar to or higher than that of lower density arrays. In addition, the minor allele frequency of SNPs in the reference population affected the accuracy. The accuracy increased as the size of the reference population increased, up to 400 animals, beyond which there was little increase. A higher genetic relationship between the reference and test populations increased imputation accuracy. These results indicate that high imputation accuracy can be achieved using high-density arrays, having enough reference animals and including relatives in the reference population. PMID- 26156251 TI - Plant protein-based delivery systems for bioactive ingredients in foods. AB - The application of food-grade delivery systems for the encapsulation, protection and controlled release of bioactive food ingredients have recently gained increasing interest in the research fields of functional foods and pharmaceutics. Plant proteins (mainly soy proteins, zein and wheat gliadins), which are widely available and environmentally economic compared to animal derived proteins, can be made into various delivery platforms, such as micro- and nanoparticles, fibers, films and hydrogels. In this paper, we review the recent progress in the preparation of food-grade delivery systems based on plant proteins for bioactive ingredients, and highlight some of the challenges and directions that will be the focus of future research. The preparation and application of bifunctional particles, which were able to deliver the bioactives to oil/water interface and stabilize the interface, are also described, providing a novel perspective for the design of plant protein-based delivery system. PMID- 26156252 TI - Assessment of Long-Term Outcomes in Hbs Ag-Negative Renal Transplant Recipients Transplanted from Hbs Ag-Positive Donors. AB - BACKGROUND: The aim of this study was to evaluate the long-term outcomes of renal transplantation from Hbs Ag-positive donors to Hbs Ag-negative recipients. MATERIAL AND METHODS: A total of 78 patients who underwent renal transplantation in our clinic between January 2006 and May 2014 were included in the study. Patients were divided into 2 groups: Group 1: Donor Hbs Ag (+) (n=26, Hbs Ab (-), Hbe Ag (-), Hbe Ab (+), Hbc Ig total (+) and HBV DNA (+), male/female (M/F): 16 (61.5%)/10 (38.5%), and Group 2: Donor Hbs Ag (-) (n=52, M/F: 41 (78.8%)/11 (21.2%). Hbs Ab levels were similar in recipients in both groups. Data were collected retrospectively. Analyses were performed by using SPSS 20.0 software, and patient and graft survival were measured by using Kaplan-Meier survival curve and compared by using the log-rank test. RESULTS: Demographic data were similar in the 2 groups. The rate of acute Hepatitis B infection was significantly higher in Group 1 than in Group 2 [n=3 (11.5%) vs. n=0 (0%), respectively, p=0.012]. Acute hepatitis B attacks were detected in vaccinated patients. Graft survival rates (groups 1 and 2, respectively; at 1st, 3rd, 5th and 8th years: 95% vs. 96%, 95% vs. 94%, 85% vs. 88%, 85% vs. 82%, p=0.970) and patient survival rates (p=0.098), acute rejection rates (p=0.725), delayed graft function, chronic allograft dysfunction, new-onset diabetes after transplantation (NODAT), cytomegalovirus infection, and the need for postoperative dialysis and plasmapheresis were similar between groups. CONCLUSIONS: Our study revealed that the risk of developing acute hepatitis B was higher in patients renally transplanted from Hbs Ag (+) donors, but the other clinical outcomes were similar between groups. PMID- 26156253 TI - A model for integrating the assessment and management of geriatric syndromes into internal medicine continuity practice: 5-year report. AB - A geriatric ambulatory curriculum was created to improve internal medicine residents' care of geriatric patients. Second-year residents met for a 3-hour session weekly for 4 consecutive weeks during a block rotation with faculty geriatricians for a curriculum focused on dementia, falls, and urinary incontinence. After a 1-hour case-based didactic session, residents applied learned content and concepts to patient consultations. Consultative encounters were precepted by faculty and shared with the team. After completing our curriculum, residents reported knowledge acquired and enhanced evaluation and management skills of these three syndromes and were more likely to use all recommended screening tests in future practice. This article describes the process and strategies guiding development of a successful ambulatory geriatric curriculum model that can be embedded into preexisting internal medicine clinics to help future internists to better manage these and other common geriatric syndromes. PMID- 26156254 TI - [Natalizumab treatment in multiple sclerosis]. AB - Multiple sclerosis is a neurodegenerative and inflammatory immune disorder in the central nervous system (CNS). Most patients show relapse-remitting clinical course. Some disease modifying medications for preventing the relapses including natalizumab (NTZ) are approved in Japan. Natalizumab (NTZ), a monoclonal antibody against alpha4 integrin present on the surface of lymphocytes, inhibits the binding of lymphocytes to vascular cell adhesion molecule-1 (VCAM-1) of endothelial cells and blocks the penetration of encephalitogenic T cells into the CNS. This review provides an update on the efficacy of an inhibition of relapses, adverse effects including progressive multifocal leukoencephalopathy, treatment after NTZ discontinuation, and body weight based treatment. PMID- 26156255 TI - [Case of 55-year-old female with primary central nervous system lymphoma, presenting with brain and eye lesions and long-term relapsing/remitting course]. AB - We report the case of a 55-year-old immunocompetent female with primary central nervous system lymphoma (PCNSL). Seven years previously, the patient presented with left facial dysesthesia, and a right thalamus lesion was revealed by brain MRI. Both her dysesthesia and the lesion disappeared spontaneously in six months. One year previously, she noted motor disturbance of the right limbs, and brain MRI revealed lesions in the bilateral basal ganglia and the left internal capsule which gradually increased in size. She was admitted to our hospital owing to the brain MRI findings of a white matter lesion in the left occipital lobe and bilateral optic neuritis. Previously, she had experienced two episodes of steroid responsive uveitis in her left eye. An inflammatory disease such as multiple sclerosis was initially suspected because of the relapsing/remitting clinical course with a long time interval. Treatment with corticosteroids improved her clinical symptoms and decreased the size of the lesions, but the brain lesions and bilateral optic neuritis recurred within one month. At that time, the beta2 microglobulin level in the cerebrospinal fluid was high and the left occipital lobe lesions showed increased 18F-fluoro-deoxyglucose uptake in positron emission tomography and decreased Cho/NAA ratio in 1H-MR spectroscopy. These findings suggested PCNSL. A brain biopsy confirmed the presence of diffuse large B cell lymphoma. Both uveitis and optic neuritis were considered to be caused by intraocular lymphoma associated with PCNSL. Although patients with PCNSL may experience temporary spontaneous remission, our present case suggests that the time interval from remission to relapse can be much longer than generally expected. We suggest that it is necessary to consider PCNSL and perform a brain biopsy on patients presenting with atypical clinical manifestations of an inflammatory disease, even in cases with a long clinical course. PMID- 26156256 TI - [Radiation-induced lumbosacral plexopathy with severe burning pain after 17 years of radiation therapy for cervical cancer: a case report]. AB - A 73-year-old woman was admitted with severe burning pain, hyperesthesia, and weakness in the right lower extremity. The patient had undergone radio- and chemotherapy after surgery for cervical cancer 17 years earlier. We diagnosed radiation-induced lumbosacral plexopathy because of conduction block in the deep peroneal nerve and myokymic discharge in the tibialis anterior muscle. Pelvic computed tomography and magnetic resonance imaging ruled out recurrent tumor and nerve-compressing lesions. Although radiation-induced lumbosacral plexopathy is usually characterized by lower motor neuron syndrome, we report a rare case presenting with severe pain and hyperesthesia. PMID- 26156257 TI - [A case-series study on clinical presentation, neuroradiological characteristics, and outcome of 56 consecutive patients suspected of having spontaneous intracranial hypotension]. AB - The author reviewed the clinical records and neuroradiologic examinations of 86 consecutive patients with orthostatic headache who visited our clinic between April 1995 and December 2014. Fifty-six patients were suspected to have spontaneous intracranial hypotension (SIH). The baseline characteristics of these patients were essentially similar to those reported in other published case series of SIH: female preponderance, mean age of approximately 40 years, and frequent association with nausea, hearing disturbances, or vertigo. In 43 patients who underwent gadolinium-enhanced MRI, 15 had partial dural enhancement and 15 had diffuse enhancement. Of 13 patients who underwent radionuclide cisternography, a direct finding of cerebrospinal fluid (CSF) leakage was demonstrated in six patients. Ordinal scales were formulated for regression of the extent of dural enhancement on cranial MRI (none: 0, partial: 1, diffuse: 2) and severity of orthostatic headache (not so severe: 1, severe: 2). Ordinal logistic regression analysis demonstrated that the extent of dural enhancement was negatively associated with the severity of orthostatic headache. A possible explanation was that patients suspected of having SIH who showed severe orthostatic headache may lack the ability to compensate for CSF loss. Epidural blood patch (EBP) is targeted at the CSF leak site or at the lumbar level when the site of CSF leak has not been determined. The interval from EBP to disappearance of orthostatic headache did not significantly differ in six patients treated with targeted EBP and five patients with lumbar EBP. Linear regression analysis demonstrated that the duration of orthostatic headache was associated with the interval from onset of headache to initial visit to our clinic, with the slope of the regression line 1.243 and intercept 14.8 days. Thus, early diagnosis of SIH appeared to correlate with earlier disappearance of orthostatic headache. No other factors were found to predict the outcome of SIH. PMID- 26156258 TI - [Clinical, epidemiological and etiological studies of adult aseptic meningitis: Report of 13 cases with mumps meningitis]. AB - We experienced 13 cases (29.8 +/- 7.0 years) of mumps meningitis and 365 cases of adult aseptic meningitis during 11 years from 2004 to 2014. A small epidemic of mumps occurred for 3-4 years, and the incidence rate of adult mumps meningitis coincided with the epidemic without seasonal fluctuation. Parotitis was observed in 8 of the 13 mumps meningitis patients (61.5%) and orchitis in 2 of 7 male patients (28.6%). There were no differences in clinical manifestations, laboratory findings, and outcome between patients with adult mumps meningitis and those with echovirus 9 meningitis (9 patients), except for the low frequency of nausea/vomiting and a high percentage of mononuclear cells of the cerebrospinal fluid in those with mumps. Eight patients had contact with persons with mumps before the symptomatic stage of meningitis. Only one patient had received mumps vaccination in childhood. On the basis of the values of the anti-mumps IgM and IgG antibodies, we speculated primary infection and the re-infection of mumps in 6 and 2 patients, respectively. Moreover, second vaccine failure was suggested in the vaccinated patient. PMID- 26156259 TI - [Survey of the actual state of medical care of patients with Duchenne muscular dystrophy in Japan]. AB - It has been suggested that many physicians feel it is difficult to manage patients with Duchenne muscular dystrophy (DMD) and that support from experts is required. Therefore, to assess the effects of Japanese practical guidelines for DMD, we distributed a survey questionnaire to certified neurologists and child neurologists in Japan. The survey revealed the actual state of medical care for patients with DMD in Japan prior to publication of guidelines. Many pediatric patients visited academic medical centers (AMCs) and general hospitals (GHs). In contrast, adult patients visited mainly National Hospital Organization (NHO) hospitals and other hospitals that can manage cardiopulmonary care and inpatient therapy. Medical insurance approval for steroid therapy was well known by subjects surveyed. Beta-blockers and angiotensin converting enzyme inhibitors were widely used as cardioprotective agents. However, the rates of obtaining written informed consent before genetic testing, regular radiological testing for scoliosis, usage of mechanical-assisted cough, disaster response plan instruction for patients receiving mechanical ventilation, and management of patients with female dystrophinopathy were below satisfactory. More than 20% of doctors surveyed practiced or recommended muscle strengthening training. Although the details of the training were not specified, this may indicate overuse of resistance training exercises. Our goal is to promote an educational campaign to better disseminate best practice care and clinical guidelines. We plan to conduct another round of surveys in several years to assess the effects of the clinical guidelines. PMID- 26156260 TI - Outcomes of hospitalized neutropenic oncology patients with Pseudomonas aeruginosa bloodstream infections: focus on oral fluoroquinolone conversion. AB - BACKGROUND: Pseudomonas aeruginosa bacteremia is a major cause of morbidity and mortality, especially in neutropenic oncology patients. Few studies have been published in the last decade on treatment outcomes of neutropenic oncology patients with Pseudomonas aeruginosa bacteremia. In addition, there is a lack of data addressing the role of oral fluoroquinolones in this patient setting. METHODS: A retrospective chart review from 1999 to 2013 was conducted at a large academic medical center in neutropenic oncology patients with documented Pseudomonas aeruginosa bacteremia, who were initially treated with intravenous anti-pseudomonal antibiotics and then converted to an oral anti-pseudomonal fluoroquinolone. Patients were evaluated for the rate of cure and for the time from onset of intravenous antibiotic therapy to conversion to oral fluoroquinolones. RESULTS: Twenty-nine patients with Pseudomonas aeruginosa bacteremia were evaluated. The median absolute neutrophil count at the time of the first positive blood culture was 50 cells/mm(3), and the median duration of time below an absolute neutrophil count of 1000 cells/mm(3) was five days. The change to oral fluoroquinolones occurred at a median (range) of six (2-18) days after initiation of intravenous antibiotics and at a median absolute neutrophil count of 2610 (110-24790) cells/mm(3). The initial cure was 93.1%, while ultimate cure was 91.7%. CONCLUSION: Converting to oral fluoroquinolones after initial intravenous antibiotic therapy for Pseudomonas aeruginosa bacteremia in clinically stable neutropenic oncology patients appears to achieve successful outcomes. However, prospective trials are needed to validate these results in neutropenic oncology patients with Pseudomonas aeruginosa bacteremia who are converted to oral fluoroquinolones. PMID- 26156261 TI - "I Want to Come Home": Vietnam-Era Veterans' Presenting for Mental Health Care, Roughly 40 Years After Vietnam. AB - There continues to be an increase in the number of Vietnam-era veterans receiving a diagnosis of PTSD in the Veterans Health Administration, nearly four decades after Vietnam. In the present study, our aim was to better understand what prompts Vietnam-era veterans to present to a VHA mental health clinic, and to determine the meaning of this experience for them. Participants were interviewed regarding the experiences that prompted their visit to the mental health clinic at a VA medical center. Ensuing narratives were analyzed via phenomenological qualitative methods. Findings revealed that veterans did not hold a clear and determinate understanding of "PTSD" prior to attending the mental health clinic. Their engagement was instead the culmination of a long process wherein trusted others (e.g., family, other veterans, primary care doctors) suggested that their difficulties may be indicative of a problematic pattern that required attention beyond the everyday ways of dealing with them. In general, veterans suffered from a longstanding experience of social rejection, abandonment, and even betrayal following the war, including pervasive stigmatizations and perceived "weaknesses," and their own preferences for self-reliance over inattentive social and governmental institutions. Many veterans were newly focused on renewing meaning and purpose in their lives. The findings suggest the need to build stronger bridges between the VA and veterans' community supports, who greatly influenced veterans' care seeking. Further efforts to welcome Vietnam-era veterans home, validate their experiences of rejection and abandonment, and respectfully process their ensuing pain and anger are warranted. PMID- 26156263 TI - Editorial: Therapeutic Potential of microRNAs in Vascular Disease. AB - Cardiovascular disease has become the predominant cause of human morbidity and mortality in the industrialized world, devouring extraordinary efforts to determine the molecular and pathophysiological characteristics of the diseased heart and vasculature, while aiming to develop novel diagnostic and therapeutic strategies to treat the associated diseases. The collective work of multiple research groups has uncovered a complex transcriptional and posttranscriptional regulatory circuit, which is believed to be essential for maintaining vascular homeostasis. Recently, a novel class of small noncoding RNAs, called microRNAs, was identified as powerful posttranscriptional regulators, orchestrating the translational output of target messenger RNAs (mRNAs) by promoting mRNA degradation and/or inhibiting translation. With the discovery of microRNAs being powerful modulators in a wide variety of diseases, it is only a logical consequence that the possibilities of viewing microRNAs as promising therapeutic entities are being heavily investigated. PMID- 26156262 TI - To brood or not to brood: Are marine invertebrates that protect their offspring more resilient to ocean acidification? AB - Anthropogenic atmospheric carbon dioxide (CO2) is being absorbed by seawater resulting in increasingly acidic oceans, a process known as ocean acidification (OA). OA is thought to have largely deleterious effects on marine invertebrates, primarily impacting early life stages and consequently, their recruitment and species' survival. Most research in this field has been limited to short-term, single-species and single-life stage studies, making it difficult to determine which taxa will be evolutionarily successful under OA conditions. We circumvent these limitations by relating the dominance and distribution of the known polychaete worm species living in a naturally acidic seawater vent system to their life history strategies. These data are coupled with breeding experiments, showing all dominant species in this natural system exhibit parental care. Our results provide evidence supporting the idea that long-term survival of marine species in acidic conditions is related to life history strategies where eggs are kept in protected maternal environments (brooders) or where larvae have no free swimming phases (direct developers). Our findings are the first to formally validate the hypothesis that species with life history strategies linked to parental care are more protected in an acidifying ocean compared to their relatives employing broadcast spawning and pelagic larval development. PMID- 26156264 TI - Therapeutic Potential of Modulating microRNAs in Atherosclerotic Vascular Disease. AB - Atherosclerosis (also known as arteriosclerotic vascular disease) is a chronic inflammatory disease of the arterial wall, characterized by the formation of lipid-laden lesions. The activation of endothelial cells at atherosclerotic lesion-prone sites in the arterial tree results in the up-regulation of cell adhesion molecules and chemokines, which mediate the recruitment of circulating monocytes. Accumulation of monocytes and monocyte-derived phagocytes in the wall of large arteries leads to chronic inflammation and the development and progression of atherosclerosis. The lesion experiences the following steps: foam cell formation, fatty streak accumulation, migration and proliferation of vascular smooth muscle cells, and fibrous cap formation. Finally, the rupture of the unstable fibrous cap causes thrombosis in complications of advanced lesions that leads to unstable coronary syndromes, myocardial infarction and stroke. MicroRNAs have recently emerged as a novel class of gene regulators at the post transcriptional level. Several functions of vascular cells, such as cell differentiation, contraction, migration, proliferation and inflammation that are involved in angiogenesis, neointimal formation and lipid metabolism underlying various vascular diseases, have been found to be regulated by microRNAs and are described in the present review as well as their potential therapeutic application. PMID- 26156266 TI - Editorial: microRNAs: Potential Targets for the Treatment of Cardiovascular Disease. AB - Several non-coding microRNAs (miRs) are implicated in the pathogenesis of obesity, metabolic syndrome, diabetes mellitus, atherosclerosis and cardiovascular disease. Some of these miRs are beneficial but others are hazardous. Silencing of the latter by antisense oligonucleotides has been attempted in animal models with promising results. However, the replacement of down-regulated beneficial miRs, by manufactured miR mimics, or increasing their expression is much more demanding and has several limitations. The treatment of cardiovascular diseases through miR manipulation shows potential, provided safety and cost effectiveness issues are considered carefully before implementation in humans. PMID- 26156267 TI - New therapeutic effects of cilostazol in patients with ischemic disorders. AB - Cilostazol (CIL) is effective for the treatment of patients with peripheral arterial disease (PAD). CIL is an orally administered drug with multiple effects, including anti-platelets aggregation, favorable functions on plasmatic lipids and vasodilator ones, but how these effects might be related to improvement in patients walking affected by PAD is not fully understood. The latest data demonstrate that nitric oxide (NO) is induced by CIL through endothelial nitric oxide synthase (eNOS) activation via a cyclic-AMP (cAMP)/ protein kinase A (PKA)- and PI3K/Akt- dependent mechanism. This mechanism is also responsible for the vasodilatation dependent on endothelium which characterized patients receiving CIL. Other investigators have found that CIL notably reduces the exercise-induced host-inflammatory response in PAD patients, and consequently it improves lipid hydroperoxides and cell-adhesion molecule levels. We recently reported that CIL is able to cause neoangiogenesis in vivo by stimulating the production of proangiogenic proteins, such as vascular endothelial growth factor (VEGF), that increase levels of Endothelial progenitor cells (EPCs) and the formation of new blood vessels. The mechanisms of action of this drug are several and are not clear and established. The objective of the present review is to analyze the existing data about the therapeutic effects of CIL, with the purpose of providing practical indications about this topic for the management of subjects affected by ischemic disorders. PMID- 26156268 TI - Scientific delinquencies. PMID- 26156269 TI - Effectiveness of new vibration delivery system on pain associated with injection of local anesthesia in children. AB - AIM: Pain is highly subjective and it is neurologically proven that stimulation of larger diameter fibers - e.g., using appropriate coldness, warmth, rubbing, pressure or vibration - can close the neural "gate" so that the central perception of itch and pain is reduced. This fact is based upon "gate control" theory of Melzack and Wall. The present study was carried out to investigate the effects of vibration stimuli on pain experienced during local anesthetic injections. MATERIALS AND METHODS: Thirty patients aged 6-12 years old of both the genders with Frankel's behavior rating scale as positive and definitely positive requiring bilateral local anesthesia injections for dental treatment were included in the split-mouth cross over design. Universal pain assessment tool was used to assess the pain with and without vibration during the administration of local anesthesia and the results obtained were tabulated and statistically analyzed. RESULTS: Local anesthetic administration with vibration resulted in significantly less pain (P = 0.001) compared to the injections without the use of vibe. CONCLUSION: The results suggest that vibration can be used as an effective method to decrease pain during dental local anesthetic administration. PMID- 26156270 TI - Knowledge and attitude in regards to physical child abuse amongst medical and dental residents of central Gujarat: a cross-sectional survey. AB - CONTEXT: Child abuse is a state of emotional, physical, economic, and sexual maltreatment met out to a person below the age of 18 and is a globally prevalent phenomenon. However, in India, there has been no understanding of the extent, magnitude, and trends of the problem. AIMS: The aim of this study was to determine the level of knowledge and attitudes of medical and dental residents with regards to physical child abuse of central Gujarat. MATERIALS AND METHODS: A cross-sectional survey was conducted among the medical and dental residents of central Gujarat. Data were collected from a self-administered questionnaire for a total of 130 residents, in which 89 medical and 41 dental residents responded. RESULTS: Knowledge regarding the social indicator of child abuse was found to be poor in 27.7% (n = 36), average in 68.5% (n = 89), and good in 3.8% (n = 5); and for physical indicator it was found to be poor in 10.8% (n = 14), average 66.9% (n = 87), and good 22.3% (n = 29). Forty-nine percent (n = 64) of the respondents reported having formal training in recognizing child abuse, and 32% (n = 42) had read literature on the topic. Fifty-five percent (n = 72) stated that education regarding child abuse is extremely important. CONCLUSIONS: Result of the present study found that medical and dental residents are not sufficiently prepared to endure their role in protection of child from abuse. A significant gap existed between recognizing signs of physical child abuse and responding effectively. Improvements in child abuse education and continuing education courses are advised to provide adequate knowledge. PMID- 26156265 TI - Angiogenesis-regulating microRNAs and Ischemic Stroke. AB - Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and poststroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis. PMID- 26156271 TI - Finite element stress analysis of stainless steel crowns. AB - BACKGROUND: Though stainless steel crowns (SSCs) have often been stated as the best restorative modality, there are limited studies demonstrating its efficacy in restoring the functional integrity of the primary dentition. Hence has arisen, the necessity to establish the supremacy of SSCs. AIM: Evaluation of the efficacy of SSC to with stand compressive (0 degrees ), shearing (90 degrees ), and torsional (45 degrees ) stress when used as a restorative material. SETTINGS AND DESIGN: The study design employed four finite element models, each with differing amounts of tooth structure, which were exported to ANSYS software and subjected to an average simulated bite force of 245N. MATERIALS AND METHODS: Four maxillary deciduous primary molars restored with SSCs (3M ESPE) were subjected to spiral computed tomography (CT) in order to obtain three-dimensional (3D) images, which were then converted into finite element models. They were each subjected to forces along the long axis of the tooth and at 45 degrees and 90 degrees . RESULTS: The maximal equivalent von Mises stress was demonstrated in the SSCs of all the models with only a minimal amount observed in the underlying dentine. In all situations, the maximal equivalent von Mises stress was well below the ultimate tensile strength values of stainless steel and dentine. CONCLUSION: Even at maximal physiologic masticatory force levels, a grossly destructed tooth restored with SSC is able to resist deformation. PMID- 26156272 TI - Comparative evaluation of the effectiveness of audio and audiovisual distraction aids in the management of anxious pediatric dental patients. AB - OBJECTIVE: The aim of this study was to evaluate and compare audio and audiovisual distraction aids in management of anxious pediatric dental patients of different age groups and to study children's response to sequential dental visits with the use of distraction aids. STUDY DESIGN: This study was conducted on two age groups, that is, 4-6 years and 6-8 years with 30 patients in each age group on their first dental visit. The children of both the age groups were divided into 3 subgroups, the control group, audio distraction group, audiovisual distraction group with 10 patients in each subgroup. Each child in all the subgroups had gone through three dental visits. Child anxiety level at each visit was assessed by using a combination of anxiety measuring parameters. The data collected was tabulated and subjected to statistical analysis. RESULTS: Tukey honest significant difference post-hoc test at 0.05% level of significance revealed audiovisual group showed statistically highly significant difference from audio and control group, whereas audio group showed the statistically significant difference from the control group. CONCLUSION: Audiovisual distraction was found to be a more effective mode of distraction in the management of anxious children in both the age groups when compared to audio distraction. In both the age groups, a significant effect of the visit type was also observed. PMID- 26156273 TI - Comparative evaluation of smear layer removal by various chemomechanical caries removal agents: an in vitro SEM study. AB - OBJECTIVES: To comparatively evaluate the efficiency of various chemomechanical caries removal agents in smear layer removal. MATERIALS AND METHODS: Class V cavities were prepared on the buccal surface of 45 extracted, noncarious molars and were divided into three groups according to the chemical treatment received. The samples were then gold palladium coated and viewed under scanning electron microscope. The presence of smear layer was evaluated based on the microscopic observations. Result and Observation: The results indicated that smear layer removal was significantly higher in the sodium hypochlorite-based chemomechanical caries removal agents than in the papain-based chemomechanical caries removal agent and was least in the control group treated with saline. CONCLUSION: The smear layer removal was maximum with Carisolv followed by the cariecare and was minimum in the saline-treated group. PMID- 26156274 TI - Comparative evaluation of adequacy of final working length after using Raypex5 or radiography: an in vivo study. AB - AIM: The aim of this clinical study was to compare the effect of working length (WL) determination using electronic apex locator (EAL) or WL radiograph on the length adequacy of final WL. MATERIALS AND METHODS: A total of 153 patients with 153 teeth with single canal were randomized into two groups; in Group 1, the WL was determined by WL radiograph; whereas in Group 2, it was determined by the Raypex5 EAL (VDW, Munich, Germany). Length adequacy was assessed in each group for master cone and categorized into short, acceptable, and over cases. STATISTICAL ANALYSIS USED: The data were statistically analyzed using the Pearson chi-square test at a significance level of P < 0.05. RESULTS: There was no statistically significant difference between the groups in the rates of acceptable (Group 1 = 83.1% and Group 2 = 92.1%) and short cases (Group 1 = 3.9% and Group 2 = 5.2%). Over cases in master cone radiography were significantly more in Group 1 (13.1%) than Group 2 (2.6%) (P = 0.017). CONCLUSION: The results of our study have shown that under clinical condition, success of Raypex5 was comparable to the radiographic WL determination technique in terms of acceptable and short cases. However, there were significantly lesser over cases in EAL group, showing that EALs can avoid the overestimation of WL. PMID- 26156275 TI - Prevalence and severity of molar incisor hypomineralization in children aged 11 16 years of a city in Karnataka, Davangere. AB - INTRODUCTION: Molar incisor hypomineralization (MIH) describes the clinical picture of hypomineralization of systemic origin affecting one or more first permanent molar. There is a rarity of prevalence studies in Indian population. OBJECTIVES: The main aim of this study was to investigate the prevalence of MIH in a population of South Indian children. SETTINGS AND DESIGN: A cross-sectional epidemiological survey, included 2000 children aged 11-16 years chosen by stratified random sampling from government and private schools of Davangere, a city in South India. MATERIALS AND METHODS: Evaluation of MIH and decayed, missing and filled teeth was carried out in these children by a calibrated examiner. The severity of hypomineralization was recorded according to the Wetzel and Reckel scale. STATISTICAL ANALYSIS: Chi-square test was used to analyze the categorical data. P <= 0.05 was considered for statistical significance. RESULTS: About 8.9% of all examined children showed at least one ill-structured first permanent molar in terms of MIH. The male and female ratio was found to be 1:1.1. The decreasing order of occurrence of MIH affected teeth were permanent maxillary molars, maxillaryincisors, mandibular molars and the mandibular incisors. CONCLUSION: The prevalence of MIH in the permanent dentition of south Indian children was 8.9%. There is a need for a proper planned preventive and restorative program with regard to the increasing prevalence of MIH. PMID- 26156276 TI - Effect of different oral hygiene measures on oral malodor in children aged 7-15 years. AB - PURPOSE: To evaluate the effect of various oral hygiene measures individually and in combination in reducing oral malodor. MATERIALS AND METHODS: A total number of 120 children diagnosed as having oral malodor (oral malodor scores 2 and above) were included in the study. Children were then grouped under four oral hygiene categories (tooth brushing, tongue cleaning, mouth rinsing, and a combination group). There were 30 children in each group. The children were asked to perform oral hygiene methods individually and in combination. The children were then reassessed for oral malodor 2 h later. The results were analyzed and compared. RESULTS: Both individual oral hygiene measure or in combination of tooth brushing, tongue cleaning, and mouth rinsing; all were effective in reducing oral malodor. Significant reduction (P < 0.05) in oral malodor was seen when all three oral hygiene measures performed together. CONCLUSION: Oral malodor was significantly reduced after performing oral hygiene measures individually, but reduced more when used in combination. PMID- 26156277 TI - Behavioral response and pain perception to computer controlled local anesthetic delivery system and cartridge syringe. AB - AIM: The present study evaluated and compared the pain perception, behavioral response, physiological parameters, and the role of topical anesthetic administration during local anesthetic administration with cartridge syringe and computer controlled local anesthetic delivery system (CCLAD). DESIGN: A randomized controlled crossover study was carried out with 120 children aged 7-11 years. They were randomly divided into Group A: Receiving injection with CCLAD during first visit; Group B: Receiving injection with cartridge syringe during first visit. They were further subdivided into three subgroups based on the topical application used: (a) 20% benzocaine; (b) pressure with cotton applicator; (c) no topical application. Pulse rate and blood pressure were recorded before and during injection procedure. Objective evaluation of disruptive behavior and subjective evaluation of pain were done using face legs activity cry consolability scale and modified facial image scale, respectively. The washout period between the two visits was 1-week. RESULTS: Injections with CCLAD produced significantly lesser pain response, disruptive behavior (P < 0.001), and pulse rate (P < 0.05) when compared to cartridge syringe injections. Application of benzocaine produced lesser pain response and disruptive behavior when compared to the other two subgroups, although the result was not significant. CONCLUSION: Usage of techniques which enhance behavioral response in children like injections with CCLAD can be considered as a possible step toward achieving a pain-free pediatric dental practice. PMID- 26156278 TI - Apgar index as a probable risk indicator for enamel defects in primary dentition: a cross sectional study. AB - AIM: The aim of the present study was to investigate the association of Apgar index with that of enamel defects and to explore gender predilection as a co variable in the formation of enamel defects. MATERIALS AND METHODS: A random sample of 108 individuals (46 boys and 62 girls) aged 4-5 years (mean - 4.4 years) were included in the study. A questionnaire containing subject's demographic information, Apgar Index (AI), enamel hypoplasia and hypocalcification was collected. Intraoral examination of the subjects was performed by using the type III diagnostic criteria recommended by WHO for oral health surveys. According to the modified index for developmental enamel defects, visual and tactile examinations of the entire primary dentition were performed.The data obtained was analysed using chi-square test. RESULTS: Of all the examined individuals 18 (16.7%) showed enamel defects, of which 10 (9.3%) were having enamel hypoplasia, 4 (3.7%) were having enamel hypocalcification and 4 (3.7%) were having both. Correlation of the enamel defects such as hypoplasia, hypocalcification and both had no significant relationship with the gender (P = 0.36). CONCLUSION: Subjects with lower Apgar Index exhibited more hypoplastic and hypocalcified teeth both qualitatively and quantitatively. If the Apgar value is less than 6, the vulnerability for the development of enamel defects has considerably increased. Gender of the individuals did not influence the final outcome. PMID- 26156279 TI - Psychometric properties of the Malayalam version of ECOHIS. AB - BACKGROUND: The Early Childhood Oral Health Impact Scale (ECOHIS) has been developed in English for determining oral health-related quality of life (OHRQoL) in the preschool children. It has been translated and validated in different languages to suit different cultures. The ECOHIS is, till date, the only tool available for research in this field on preschool age children. A similar version of this tool is not available for use in the local language Malayalam. AIM: This study aimed to develop and validate a Malayalam version of the ECOHIS (M-ECOHIS). DESIGN: The study was conducted with a cross-sectional design. The ECOHIS was translated into Malayalam by forward-backward translation and tested for face and content validity. The parents of 300 children were administered the M-ECOHIS and an additional global oral health (GOH) question. The children were examined for the presence of early childhood caries (ECC) which was recorded using the defs index. The internal consistency reliability, test-retest reliability, interobserver reliability, and convergent and discriminant validity were assessed. RESULTS: The tool possessed good internal consistency (Cronbach's alpha = 0.879; item total correlation 0.2832-0.7617); the test-retest reliability and interobserver reliability assessed using ICC (ICC = 0.9457 and 0.9460, respectively) was acceptable. The Spearman's correlation coefficient of the ECOHIS and the GOH scores, r = 0.725; P = 0.01 supported the convergent validity. The mean ECOHIS scores of children having ECC with mean ECOHIS scores of children without ECC were compared using unpaired t-test and found to be statistically significant supporting the discriminant validity of the scale. CONCLUSION: The M ECOHIS can be used to assess the OHRQoL of preschool children in the Malayalam speaking community. PMID- 26156280 TI - Evaluation of nitrous oxide inhalation sedation during inferior alveolar block administration in children aged 7-10 years: a randomized control trial. AB - BACKGROUND: Nitrous oxide-oxygen (N 2 O-O 2 ) is being used in combination with many drugs and this possess risk for leading to deep sedation or reflexes being compromised. AIM: The purpose of our study was to use N 2 O-O 2 alone, to evaluate its effectiveness for pain control during inferior alveolar nerve block administration in children. DESIGN: This was a single-centered, simple randomized, double-blinded, placebo-controlled parallel-group study involving 40 children in the age group of 7-10 years divided into 2 groups: N 2 O-O 2 sedation and oxygen. Pain perception for local anesthesia was assessed using face, legs, activity, cry, consolability scale. Children's behavior was assessed using Frankl ratings, depth of sedation using Observer's Assessment of Alertness/Sedation scale. The vital signs and oxygen saturation were recorded. RESULTS: There was a significantly lower pain reaction to local anesthetic administration in the N 2 O O 2 group (P < 0.01). Improvement in the behavior of the children belonging to N 2 O-O 2 group during and after the procedure as compared to the O 2 group (P < 0.01) was also observed. All the vital signs recorded were in the normal physiologic limits in both the groups. CONCLUSION: Pain experienced by children receiving N 2 O-O 2 sedation was significantly lower. N 2 O-O 2 inhalation sedation produces adequate sedation with vital signs within normal limits and treatments successfully completed. PMID- 26156281 TI - A comparative effect of various surface chemical treatments on the resin composite-composite repair bond strength. AB - AIM: The aim of this in vitro study was an attempt to investigate the effect of different surface treatments on the bond strength between pre-existing composite and repair composite resin. MATERIALS AND METHODS: Forty acrylic blocks were prepared in a cuboidal mould. In each block, a well of 5 mm diameter and 5 mm depth was prepared to retain the composite resin (FiltekTM Z350, 3M/ESPE). Aging of the composite discs was achieved by storing them in water at 37 degrees C for 1 week, and after that were divided into 5 groups (n = 8) according to surface treatment: Group I- 37% phosphoric acid, Group II-10% hydrofluoric acid, Group III-30% citric acid, Group IV-7% maleic acid and Group V- Adhesive (no etchant). The etched surfaces were rinsed and dried followed by application of bonding agent (AdperTM Single Bond 2. 3M/ESPE). The repair composite was placed on aged composite, light-cured for 40 seconds and stored in water at 37 degrees C for 1 week. Shear bond strength between the aged and the new composite resin was determined with a universal testing machine (crosshead speed of 0.5 mm/min). STATISTICAL ANALYSIS: The compressive shear strengths were compared for differences using ANOVA test followed by Tamhane's T2 post hoc analysis. RESULTS: The surface treatment with 10% hydrofluoric acid showed the maximum bond strength followed by 30% citric acid, 7% maleic acid and 37% phosphoric acid in decreasing order. CONCLUSION: The use of 10% hydrofluoric acid can be a good alternative for surface treatment in repair of composite resin restoration as compared to commonly used 37% orthophosphoric acid. PMID- 26156282 TI - Dentine in a capsule: clinical case reports. AB - Biodentine TM , a calcium silicate based material has been popular now and can be used as an alternative to mineral trioxide aggregate (MTA) due to superior physical and biologic properties. It has been known by several terms as Biodentine, dentin substitute, and RD 94. It has varied clinical applications such as apexification, apexogenesis, pulpotomy, internal resorption, root perforation repair, retrograde filling, pulp capping procedure, and dentin replacement. This article describes the clinical case reports using Biodentine in apexification, apexogenesis, pulpotomy, and root perforation repair. PMID- 26156283 TI - Early treatment of Class III malocclusion by RME and modified Tandem appliance. AB - Patients with a skeletal Class III malocclusion and maxillary deficiency can be treated successfully using a combined protraction facemask and alternate rapid maxillary expansions and contractions (Alt-RAMEC). However, due to poor patient compliance during facemask therapy there has been growing interest in intraoral appliances for correcting Class III malocclusion. The tandem traction bow appliance (TTBA) is an intraoral appliance which has been used successfully for the treatment of growing Class III patients. This case report describes the management of a 10-year-old boy with a Class III malocclusion and maxillary deficiency treated with modified TTBA appliance. PMID- 26156284 TI - Management of congenital choanal atresia: a pedodontist's role. AB - Choanal atresia is a rare cryptic congenital anomaly with developmental failure of the nasal cavity to communicate with the nasophaynx, resulting in a significant physiological and anatomical alteration of the dento-facial complex. It is considered as a life-threatening or lethal congenital malformation in an obligatory nasal breathing neonate. Elective transnasal endoscopic repair is the most preferred and minimally invasive procedure to correct this anomaly. This case report describes the multi-disciplinary team approach that included pedodontists to manage the case of a 6-month-old infant with choanal atresia suffering from breathlessness, feeding difficulty, and disturbed sleep. PMID- 26156285 TI - High Serum Osteoprotegerin Is Associated with Arterial Stiffness in Kidney Transplant Patients. AB - Osteoprotegerin (OPG) is a cytokine that regulates bone resorption by inhibiting osteoclastogenesis, and OPG has been implicated in the process that causes vascular stiffness. An increase in serum OPG level has been associated with the development of arterial stiffness. Kidney transplant (KT) patients are susceptible to aortic stiffness, which is considered to be a predictor of cardiovascular events in this patient population. Carotid-femoral pulse wave velocity (cfPWV) has emerged as a gold standard for non-invasive evaluation of aortic stiffness. The aim of this study was to evaluate the relationship between serum OPG concentration and cfPWV among KT patients. Fasting blood samples were obtained from 57 KT patients and their cfPWV was measured using applanation tonometry. The serum OPG levels were measured using an enzyme-linked immunosorbent assay. Univariable linear regression analysis showed that the cfPWV in KT patients was significantly and positively correlated with age, body weight, waist circumference, body mass index, log-creatinine, systolic blood pressure, diastolic blood pressure, pulse pressure, and the log-OPG concentration. KT patients with metabolic syndrome had higher cfPWV values than those without metabolic syndrome (P = 0.036), which indicates a higher incidence of aortic stiffness in this patient population. Multivariable forward stepwise linear regression analysis of the significant variables showed that the log-OPG (P = 0.001), the log-creatinine (P = 0.004), and the SBP (P = 0.005) remained as independent and positive predictors of cfPWV values. These findings indicate that serum OPG levels are positively associated with cfPWV in KT patients. PMID- 26156286 TI - Estimation of Vitamin D Intake Based on a Scenario for Fortification of Dairy Products with Vitamin D in a Tehranian Population, Iran. AB - OBJECTIVE: The aim of this study was to evaluate possible effects of food fortification practices on vitamin D intake in adults. DESIGN AND SETTING: This was designed as a cross-sectional, population-based study. SUBJECTS: We investigated vitamin D intake in a population-based sample of 5224 adults, using a validated food frequency questionnaire. A theoretical model was conducted to evaluate the hypothetical effects of dairy product fortification. RESULTS: Dairy had the highest mean of vitamin D intake among food groups. If all types of milk were fortified by vitamin D (42 IU/100 grams of milk), the mean intake of vitamin D would reach 132 +/- 148 (92(180)) IU/day. If both milk and yogurt were fortified to 42 IU/100 g and 89 IU/100 g, respectively, the average mean vitamin D intake from foods in this population would increase from 84 +/- 88 IU/day to 308 +/- 240 IU/day. As the fortification level increased, the proportions of young people with more than the recommended daily allowance (RDA) of vitamin D increased from 1.1% to 77.4% in men and from 1.4% to 80% in women, but none of them achieved the tolerable upper intake level (UL) of vitamin D. CONCLUSION: The proposed fortification scenario would provide enough vitamin D intakes by RDA in a population aged between 18 and 50 years (about 80% of the population), with none of them achieving ULs. PMID- 26156289 TI - Facile Decoration of Multiwalled Carbon Nanotubes with Hetero-oligophenylene Stabilized-Gold Nanoparticles: Visible Light Photocatalytic Degradation of Rhodamine B Dye. AB - A hetero-oligophenylene derivative 3 has been designed and synthesized which forms fluorescent spherical aggregates in mixed aqueous media due to its aggregation-induced emission enhancement characteristics. These fluorescent aggregates act as a ratiometric probe for the detection of gold ions in aqueous media and serve as reactors and stabilizers for the preparation of gold nanoparticles. The in situ generated gold nanoparticles have been decorated on multiwalled carbon nanotubes to form AuNPs@MWCNTs nanohybrid materials, which serve as recyclable photocatalysts for carrying out degradation of rhodamine dye in aqueous media. PMID- 26156288 TI - The Neuroprotective Effect of Erythropoietin on Rotenone-Induced Neurotoxicity in SH-SY5Y Cells Through the Induction of Autophagy. AB - Currently, the autophagy pathway is thought to be important for the pathogenesis of Parkinson's disease (PD), and the modulation of autophagy may be a novel strategy for the treatment of this disease. Erythropoietin (EPO) has been reported to have neuroprotective effects through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms, and it has also been shown to modulate autophagy signaling in an oxygen toxicity model. Therefore, we investigated the effects of EPO on autophagy markers and evaluated its neuroprotective effect on rotenone-induced neurotoxicity. We adapted the rotenone-induced neurotoxicity model to SH-SY5Y cells as an in vitro model of PD. We measured cell viability using MTT and annexin V/propidium iodide assays and measured intracellular levels of reactive oxygen species. Immunofluorescence analysis was performed to measure the expression of LC3 and alpha-synuclein. Intracellular signaling proteins associated with autophagy were examined by immunoblot analysis. EPO mono treatment increased the levels of mammalian target of rapamycin (mTOR) independent/upstream autophagy markers, including Beclin-1, AMPK, and ULK-1. Rotenone treatment of SH-SY5Y cells reduced their viability, increased reactive oxygen species levels, and induced apoptosis and alpha-synuclein expression, and simultaneous exposure to EPO significantly reduced these effects. Rotenone enhanced mTOR expression and suppressed Beclin-1 expression, indicating suppression of the autophagy system. However, combined treatment with EPO restored Beclin-1 expression and decreased mTOR expression. EPO protects against rotenone-induced neurotoxicity in SH-SY5Y cells by enhancing autophagy-related signaling pathways. The experimental evidence for the EPO-induced neuroprotection against rotenone-induced dopaminergic neurotoxicity may significantly impact the development of future PD treatment strategies. PMID- 26156287 TI - Increased Spontaneous Central Bleeding and Cognition Impairment in APP/PS1 Mice with Poorly Controlled Diabetes Mellitus. AB - Alzheimer's disease (AD) and vascular dementia (VaD) are the most common causes of dementia, and borderlines are blurred in many cases. Aging remains the main risk factor to suffer dementia; however, epidemiological studies reveal that diabetes may also predispose to suffer AD. In order to further study this relationship, we have induced hypoinsulinemic diabetes to APPswe/PS1dE9 (APP/PS1) mice, a classical model of AD. APP/PS1 mice received streptozotocin (STZ) ip at 18 weeks of age, when AD pathology is not yet established in this animal model. Cognition was evaluated at 26 weeks of age in the Morris water maze and the new object discrimination tests. We observed that STZ-induced episodic and working memory impairment was significantly worsened in APP/PS1 mice. Postmortem assessment included brain atrophy, amyloid-beta and tau pathology, spontaneous bleeding, and increased central inflammation. Interestingly, in APP/PS1-STZ diabetic mice, we detected a shift in Abeta soluble/insoluble levels, towards more toxic soluble species. Phospho-tau levels were also increased in APP/PS1-STZ mice, accompanied by an exacerbated inflammatory process, both in the close proximity to senile plaque (SP) and in SP-free areas. The presence of hemorrhages was significantly higher in APP/PS1-STZ mice, and although pericytes and endothelium were only partially affected, it remains possible that blood-brain barrier alterations underlie observed pathological features. Our data support the implication of the diabetic process in AD and VaD, and it is feasible that improving metabolic control could delay observed central pathology. PMID- 26156290 TI - Abnormal subchondral bone microstructure following steroid administration is involved in the early pathogenesis of steroid-induced osteonecrosis. AB - Loss of bone microstructure integrity is thought to be related to osteonecrosis. But the relationship between the time when bone microstructure integrity loss appears and the onset of osteonecrosis has not yet been determined. Our study demonstrated abnormal changes of subchondral bone microstructure involved in the early pathogenesis of osteonecrosis. INTRODUCTION: Using a rabbit model, we investigated the changes of subchondral bone microstructure following steroid administration to identify the onset of abnormal bone microstructure development in steroid-induced osteonecrosis. METHODS: Fifty-five adult female Japanese White rabbits (mean body weight 3.5 kg; mean age 24 months) were used and randomly divided among three time points (3, 7, and 14 days) consisting of 15 rabbits each, received a single intramuscular injection of methylprednisolone acetate (MP; Pfizer Manufacturing Belgium NV) at a dose of 4 mg/kg, and a control group consisting of 10 rabbits was fed and housed under identical conditions but were not given steroid injections. A micro-CT scanner was applied to detect changes in the trabecular region of subchondral bone of excised femoral head samples. Parameters including bone volume fraction (BV/TV), bone surface (BS), trabecular bone pattern factor (Tb.Pf), trabecular thickness/number/separation (Tb.Th, Tb.N, and Tb.Sp), and structure model index (SMI) were evaluated using the software CTAn (SkyScan). After micro-CT scans, bilateral femoral heads were cut in the coronal plane at a thickness of 4 MUm. The sections were then stained with haematoxylin-eosin and used for the diagnosis of osteonecrosis and the rate of development of osteonecrosis. RESULTS: The BV/TV, BS, Tb.Th and Tb.N demonstrated a time-dependent decline from 3, 7, and 14 days compared with the control group, while the Tb.Pf, Tb.Sp and SMI demonstrated an increase at 3, 7, and 14 days compared with the control group. For the histopathology portion, osteonecrosis was not seen 3 days after steroid treatment, but was present 7 days after treatment and was obvious 14 days after treatment. Furthermore, the rate of osteonecrosis appearing between 7 and 14 days was not significantly different. In addition, the presence and variation of BV/TV, BS, Tb.Pf, Tb.Th, Tb.N, and SMI demonstrated significant changes at 7 days compared with the control group except Tb.Sp (at 14 days) and this is the time when osteonecrosis is thought to occur in this model. CONCLUSION: This study demonstrated that osteonecrosis in rabbits is chronologically associated with changes in subchondral bone microstructure. PMID- 26156291 TI - Development of an encapsulated stem cell-based therapy for diabetes. AB - INTRODUCTION: Islet transplantation can treat the most severe cases of type 1 diabetes but it currently requires deceased donor pancreata as an islet source and chronic immunosuppression to prevent rejection and recurrence of autoimmunity. Stem cell-derived insulin-producing cells may address the shortage of organ donors, whereas cell encapsulation may reduce or eliminate the requirement for immunosuppression, minimizing the risks associated with the islet transplantation procedure, and potentially prolonging graft survival. AREAS COVERED: This review focuses on the design principles for immunoisolation devices and on stem cell differentiation into insulin-producing cell products. The reader will gain understanding of the different types of immunoisolation devices and the key parameters that affect the outcome of the encapsulated graft. Progresses in stem cell differentiation towards mature endocrine islet cells, including the most recent clinical trials and the challenges associated with the application of immunoisolation devices designed for primary islets to stem-cell products, are also discussed. EXPERT OPINION: Recent advancements in the field of stem cell derived islet cell products and immunoisolation strategies hold great promise for type 1 diabetes. However, a combination product including both cells and an immunoisolation strategy still needs to be optimized and tested for safety and efficacy. PMID- 26156292 TI - Optimized quinoline amino alcohols as disruptors and dispersal agents of Vibrio cholerae biofilms. AB - The biofilm state is an integral part of the lifecycle of many bacterial pathogens. Identifying inhibitors as molecular probes against bacterial biofilms has numerous potential biomedical applications. Here we report quinoline amino alcohol as a highly potent disruptor of V. cholerae biofilms. Additionally, was able to disperse preformed biofilms, an activity exhibited by few compounds with biofilm inhibiting activity. PMID- 26156293 TI - MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors. AB - Objective: Currently, the treatment of BRAF V600-mutated metastatic melanoma with BRAF inhibitors gives a response rate of ~ 50% with a progression-free survival of ~ 6 -- 7 months. In order to identify predictive biomarkers capable of stratifying BRAF-mutated patients at high risk of shorter response duration to anti-BRAF therapy, the authors analyzed the expression of 15 microRNAs (miRNAs) targeting crucial genes involved in melanoma biology and drug response.Research design and methods: A total of 15 miRNAs and target gene expression were investigated in 43 patients (30 BRAF-mutated, and 13 BRAF wild-type). Moreover, 20 BRAF-mutated patients treated with vemurafenib were analyzed for miRNA expression in respect to time-to-progression.Results: All miRNAs except miR-192 showed low expression in BRAF-mutated as compared with BRAF wild-type patients. In particular, miR-101, miR-221,miR-21, miR-338-3p and miR-191 resulted in significant downregulation inBRAF-mutated patients. Moreover, high expression of miR-192 and miR-193b* and low expression of miR-132 resulted in significant association with shorter progression.Conclusion: Three miRNAs were significantly associated with clinical outcome in metastatic melanoma patients. An increased understanding of the molecular assessment of BRAF-mutated melanomas could allow development of specific molecular tests able to predict response duration. PMID- 26156294 TI - Ultrasound gel dispensing: There may be more going around than centripetal acceleration. PMID- 26156295 TI - In reply: Ultrasound gel dispensing: There may be more going around than centripetal acceleration. PMID- 26156296 TI - Differential resistance of human embryonic stem cells and somatic cell types to hydrogen peroxide-induced genotoxicity may be dependent on innate basal intracellular ROS levels. AB - Previously, we demonstrated that undifferentiated human embryonic stem cells (hESC) displayed higher resistance to oxidative and genotoxic stress compared to somatic cells, but did not further probe the underlying mechanisms. Using H2O2 induced genotoxicity as a model, this study investigated whether higher resistance of hESC to oxidative and genotoxic stress could be due to lower innate basal intracellular levels of reactive oxygen species (ROS), as compared to their differentiated fibroblastic progenies (H1F) and two other somatic cell types - human embryonic palatal mesenchymal (HEPM) cells and peripheral blood lymphocytes (PBL). Comet assay demonstrated that undifferentiated hESC consistently sustained lower levels of DNA damage upon acute exposure to H2O2 for 30 min, compared to somatic cells. DCFDA and HE staining with flow cytometry showed that undifferentiated hESC had lower innate basal intracellular levels of reactive oxygen species compared to somatic cells, which could lead to their higher resistance to genotoxic stress upon acute exposure to H2O2. PMID- 26156297 TI - Genomic architecture and functional relationships of intronless, constitutively- and alternatively-spliced genes in Brachypodium distachyon. AB - Splicing and alternative splicing (AS) are widespread co- and post transcriptional regulatory processes in plants. Recently, we characterized genome wide AS landscapes and virus-induced AS patterns in Brachypodium distachyon (Brachypodium), a C3 model grass. Brachypodium plants infected with Panicum mosaic virus (PMV) alone or in mixed infections with its satellite virus (SPMV) were used for high-throughput, paired-end RNA sequencing. Here, using gene attributes of ~5,655 intronless genes, ~13,302 constitutively spliced, and ~7,564 alternatively spliced genes, we analyzed the influence of genomic features on splicing incidence and AS frequency. In Brachypodium, gene length, coding sequence length, and exon and intron number were positively correlated to splicing incidence and AS frequency. In contrast, exon length and the percentage composition of GC (%GC) content were inversely correlated with splicing incidence and AS frequency. Although gene expression status had little correlation with splicing occurrence per se, it negatively correlated to AS frequency: i.e., genes with >=5 alternatively spliced transcripts were significantly less expressed compared to genes encoding <5 alternative transcripts. Further gene set enrichment analysis uncovered unique functional relationships among nonspliced, constitutively spliced and alternatively spliced genes. PMID- 26156298 TI - A hydrodynamic mechanism for attraction of undulatory microswimmers to surfaces (bordertaxis). AB - Although small nematodes significantly impact human and animal health, agriculture, and ecology, little is known about the role of hydrodynamics in their life cycles. Using the nematode Caenorhabditis elegans as a model undulatory microswimmer, we have observed that animals are attracted to and swim along surfaces. The attraction to surfaces does not require mechanosensory neuron function. In dilute swarms, swimmers aggregate near surfaces. Using resistive force-based theory, symmetry arguments, and direct hydrodynamic simulations, we demonstrate that forces resulting from the interaction between the swimmer induced flow field and a nearby surface cause a short-range hydrodynamic torque that stirs the swimmers towards the surface. When combined with steric forces, this causes locomotion along the surface. This surface attraction may affect nematode mate and food finding behaviour and, in the case of parasitic nematodes, may facilitate host penetration. Surface attraction must be accounted for when studying animals' responses to various stimuli, and suggests means of controlling undulatory microswimmers. PMID- 26156299 TI - A structural model for the in vivo human cornea including collagen-swelling interaction. AB - A structural model of the in vivo cornea, which accounts for tissue swelling behaviour, for the three-dimensional organization of stromal fibres and for collagen-swelling interaction, is proposed. Modelled as a binary electrolyte gel in thermodynamic equilibrium, the stromal electrostatic free energy is based on the mean-field approximation. To account for active endothelial ionic transport in the in vivo cornea, which modulates osmotic pressure and hydration, stromal mobile ions are shown to satisfy a modified Boltzmann distribution. The elasticity of the stromal collagen network is modelled based on three-dimensional collagen orientation probability distributions for every point in the stroma obtained by synthesizing X-ray diffraction data for azimuthal angle distributions and second harmonic-generated image processing for inclination angle distributions. The model is implemented in a finite-element framework and employed to predict free and confined swelling of stroma in an ionic bath. For the in vivo cornea, the model is used to predict corneal swelling due to increasing intraocular pressure (IOP) and is adapted to model swelling in Fuchs' corneal dystrophy. The biomechanical response of the in vivo cornea to a typical LASIK surgery for myopia is analysed, including tissue fluid pressure and swelling responses. The model provides a new interpretation of the corneal active hydration control (pump-leak) mechanism based on osmotic pressure modulation. The results also illustrate the structural necessity of fibre inclination in stabilizing the corneal refractive surface with respect to changes in tissue hydration and IOP. PMID- 26156300 TI - The effect of intramuscular fat on skeletal muscle mechanics: implications for the elderly and obese. AB - Skeletal muscle accumulates intramuscular fat through age and obesity. Muscle quality, a measure of muscle strength per unit size, decreases in these conditions. It is not clear how fat influences this loss in performance. Changes to structural parameters (e.g. fibre pennation and connective tissue properties) affect the muscle quality. This study investigated the mechanisms that lead to deterioration in muscle performance due to changes in intramuscular fat, pennation and aponeurosis stiffness. A finite-element model of the human gastrocnemius was developed as a fibre-reinforced composite biomaterial containing contractile fibres within the base material. The base-material properties were modified to include intramuscular fat in five different ways. All these models with fat generated lower fibre stress and muscle quality than their lean counterparts. This effect is due to the higher stiffness of the tissue in the fatty models. The fibre deformations influence their interactions with the aponeuroses, and these change with fatty inclusions. Muscles with more compliant aponeuroses generated lower forces. The muscle quality was further reduced for muscles with lower pennation. This study shows that whole-muscle force is dependent on its base-material properties and changes to the base material due to fatty inclusions result in reductions to force and muscle quality. PMID- 26156301 TI - Cell-cell signalling in sexual chemotaxis: a basis for gametic differentiation, mating types and sexes. AB - While sex requires two parents, there is no obvious need for them to be differentiated into distinct mating types or sexes. Yet this is the predominate state of nature. Here, we argue that mating types could play a decisive role because they prevent the apparent inevitability of self-stimulation during sexual signalling. We rigorously assess this hypothesis by developing a model for signaller-detector dynamics based on chemical diffusion, chemotaxis and cell movement. Our model examines the conditions under which chemotaxis improves partner finding. Varying parameter values within ranges typical of protists and their environments, we show that simultaneous secretion and detection of a single chemoattractant can cause a multifold movement impediment and severely hinder mate finding. Mutually exclusive roles result in faster pair formation, even when cells conferring the same roles cannot pair up. This arrangement also allows the separate mating types to optimize their signalling or detecting roles, which is effectively impossible for cells that are both secretors and detectors. Our findings suggest that asymmetric roles in sexual chemotaxis (and possibly other forms of sexual signalling) are crucial, even without morphological differences, and may underlie the evolution of gametic differentiation among both mating types and sexes. PMID- 26156302 TI - Copper-Catalyzed Intermolecular Trifluoromethylazidation and Trifluoromethylthiocyanation of Allenes: Efficient Access to CF3-Containing Allyl Azides and Thiocyanates. AB - A mild and efficient method for copper-catalyzed trifluoromethylazidation and trifluoromethylthiocyanation of allenes was explored. A series of CF3-containing allyl azides and thiocyanates were obtained with high yields and good stereoselectivities, which can be used for further transformation to some valuable compounds. PMID- 26156303 TI - TE and DP otoacoustic emission data from an Australian cross-sectional hearing study. AB - OBJECTIVE: This paper presents a summary of otoacoustic emission (OAE) data collected as part of an Australian hearing health survey ( Carter, 2011 ; Williams et al, 2014 ) designed to: (1) examine the relationship between audiological indicators and participant characteristics, and (2) extract audiological data suitable for reference use. DESIGN: Cross-sectional cohort study. Distortion product (DP) OAE and transient evoked (TE) OAE measures. STUDY SAMPLE: Age range 11-35 years; N = 1386 participants (2672 test ears). RESULTS: Descriptive statistics for amplitude and signal-to-noise ratio (SNR) were calculated for 327 participants (589 test ears; age 13 to 32 years). DPOAE amplitudes down to the 25th percentile were > 0 dB SPL for test frequencies up to 6 kHz. TEOAE SNRs down to the 25th percentile were > 6 dB SPL up to 4 kHz. SUMMARY: This dataset can be used as a clinical reference for similar populations, providing that the same test parameters are used. CONCLUSIONS: The clinical significance of OAE testing would be greater if agreed criteria were available. These data could be pooled with other datasets to build a substantial OAE database, similar to the existing international standards for pure-tone hearing threshold levels (HTLs) ( ISO, 2000 ). PMID- 26156304 TI - Dynamic phase coexistence in glass-forming liquids. AB - One of the most controversial hypotheses for explaining the heterogeneous dynamics of glasses postulates the temporary coexistence of two phases characterized by a high and by a low diffusivity. In this scenario, two phases with different diffusivities coexist for a time of the order of the relaxation time and mix afterwards. Unfortunately, it is difficult to measure the single particle diffusivities to test this hypothesis. Indeed, although the non-Gaussian shape of the van-Hove distribution suggests the transient existence of a diffusivity distribution, it is not possible to infer from this quantity whether two or more dynamical phases coexist. Here we provide the first direct observation of the dynamical coexistence of two phases with different diffusivities, by showing that in the deeply supercooled regime the distribution of the single-particle diffusivities acquires a transient bimodal shape. We relate this distribution to the heterogeneity of the dynamics and to the breakdown of the Stokes-Einstein relation, and we show that the coexistence of two dynamical phases occurs up to a timescale growing faster than the relaxation time on cooling, for some of the considered models. Our work offers a basis for rationalizing the dynamics of supercooled liquids and for relating their structural and dynamical properties. PMID- 26156305 TI - 'Pharmacists have been left out of the loop': exploring the role of pharmacists in the management of HIV/AIDS in South Africa. AB - OBJECTIVE: The aim of this paper is to portray and critically analyse the role played by pharmacists in the management of the HIV/AIDS epidemic in South Africa. METHODS: The data used for this article originate in secondary and primary sources. They were collected by means of a documentary analysis of all relevant documents of significance as well as exploratory telephone interviews conducted with a systematic random sample of community pharmacies in Greater Johannesburg in 2004 and 2010. KEY FINDINGS: It is clear from the original strategic framework that the government envisaged pharmacists playing a significant role in the various facets of the epidemic. Following these intentions, the South African Pharmacy Council and the Pharmaceutical Society of South Africa embarked on a process of establishing AIDS Resource Centres in pharmacies. However, although in some areas pharmacists are contributing to the management of HIV/AIDS, the overall scenario revealed is that of lack of willingness to go for additional training and/or to invest in restructuring the pharmacy to 'accommodate' the activities of an 'AIDS Resource Centre' without the prospects of adequate financial gains. In a parallel process, the original, more meaningful role for pharmacists in the management of HIV/AIDS has not been featured in recent professional and governmental documentation. CONCLUSION: The reality on the ground is that of a missed opportunity as the pharmacists have not risen to the challenge and they remain on the margins, and not at the centre, of those professionals managing HIV/AIDS in South Africa. PMID- 26156306 TI - Neck Circumference and Vocal Parameters in Women Before and After Bariatric Surgery. AB - BACKGROUND: Morbidly obese patients may suffer from vocal disorders, as vocal production is directly related to the volume of the vocal tract, and the large scale accumulation of fat in this region may interfere with voice production. The aim of this study was to analyze the neck circumference, fundamental frequency, and maximum phonation time of a group of morbidly obese women before and after bariatric surgery. METHODS: An observational, longitudinal, and descriptive study was performed with patients of the Obesity and Related Diseases Surgery Unit of a university hospital. A total of 21 morbidly obese women aged 28-68 years, with a mean age of 41.33 years, participated in the study. Neck circumference was measured using a tape measure. To obtain fundamental frequency values, the patient was asked to produce the vowel [a] at normal intensity and pitch for an average period of 3 s. After recording, the participants were asked to produce the sustained vowels [a], [i], and [u] at normal intensity and pitch, with a stopwatch used to measure maximum phonation time. Eight months after surgery, patients were reassessed using the same data collecting procedures as were carried out prior to surgery. RESULTS: After surgery, there was an increase in the average value of fundamental frequency and maximum phonation time for all the vowels and a reduction in neck circumference. The differences were statistically significant. CONCLUSIONS: Weight reduction and a consequent decrease in neck circumference affected the changes in maximum phonation time and fundamental frequency values in the voices of these patients, after weight loss. PMID- 26156307 TI - Risk of Biliary Events After Selective Cholecystectomy During Biliopancreatic Diversion with Duodenal Switch. AB - BACKGROUND: Approximately 20 % of adults over 40 years of age in the USA develop cholelithiasis (Topart et al. Surg Obes Relat Dis. 9(4):526-30, 2013). Despite a higher incidence of biliary complications reported in postbariatric patients, it remains controversial whether simultaneous routine cholecystectomy should be performed during biliopancreatic diversion and duodenal switch (BPD/DS) or if a selective approach is more appropriate. The aim of this study was to evaluate incidence of biliary complications in patients who underwent BPD/DS without simultaneous cholecystectomy. METHODS: Retrospective review of all patients who underwent BPD/DS between 2006 and 2012 was performed. RESULTS: A total of 361 consecutive patients were included in the study with mean age of 44.8 years (range 20-72), mean body weight of 317.2 lbs (range 205-547), and average body mass index (BMI) of 50.5 kg/m(2) (range 34-71.4). Ninety-seven patients were males (26.8 %). Out of 239 patients who still had their gallbladder after the BPD/DS, 52 patients (22.7 %) developed subsequent biliary symptoms (13 patients (5.4 %) in the first year, 25 (11 %) in the second year, and 14 (6.1 %) beyond the second year). During the study period, 40 patients eventually underwent elective laparoscopic cholecystectomy, and 11 had urgent cholecystectomy (9 laparoscopic and 2 open). One patient underwent open common bile duct exploration for ascending cholangitis. Average follow-up was 31 months (12-72 months) with follow-up rate of 95.6 % at 12 months and 92.8 % at 18 months. CONCLUSIONS: Leaving normal gallbladder in situ after BPD/DS is associated with an acceptable risk of biliary events. Risk of developing common bile duct stones is low; however, it may create treatment challenges. PMID- 26156308 TI - Resolving the viscoelasticity and anisotropy dependence of the mechanical properties of skin from a porcine model. AB - The mechanical response of skin to external loads is influenced by anisotropy and viscoelasticity of the tissue, but the underlying mechanisms remain unclear. Here, we report a study of the main effects of tissue orientation (TO, which is linked to anisotropy) and strain rate (SR, a measure of viscoelasticity), as well as the interaction effects between the two factors, on the tensile properties of skin from a porcine model. Tensile testing to rupture of porcine skin tissue was conducted to evaluate the sensitivity of the tissue modulus of elasticity (E) and fracture-related properties, namely maximum stress (sigmaU) and strain (epsilonU) at sigmaU, to varying SR and TO. Specimens were excised from the abdominal skin in two orientations, namely parallel (P) and right angle (R) to the torso midline. Each TO was investigated at three SR levels, namely 0.007-0.015 s(-1) (low), 0.040 s(-1) (mid) and 0.065 s(-1) (high). Two-factor analysis of variance revealed that the respective parameters responded differently to varying SR and TO. Significant changes in the sigmaU were observed with different TOs but not with SR. The epsilonU decreased significantly with increasing SR, but no significant variation was observed for different TOs. Significant changes in E were observed with different TOs; E increased significantly with increasing SR. More importantly, the respective mechanical parameters were not significantly influenced by interactions between SR and TO. These findings suggest that the trends associated with the changes in the skin mechanical properties may be attributed partly to differences in the anisotropy and viscoelasticity but not through any interaction between viscoelasticity and anisotropy. PMID- 26156309 TI - Penicillium chrysogenum as a model system for studying cellular effects of methylglyoxal. AB - BACKGROUND: alpha-oxoaldehydes are formed as toxic by-products during metabolic activity. The biologically most important compound of this class, methylglyoxal, results from spontaneous phosphate elimination from dihydroxyacetone phosphate and glyceraldehyde 3-phosphate which are intermediate glycolysis products. Methylglyoxal-mediated modification of lipids, nucleic acids and proteins is known to lead to the formation of advanced glycation end products. These modifications contribute to the aetiology of severe diseases like diabetes and neurodegenerative disorders. By using simple model organisms it is possible to conveniently study the effects of methylglyoxal on cellular processes. Here, results are presented on the effects of methylglyoxal on mycelium growth, stationary phase entry (monitored by autophagy induction), mitochondrial morphology and protein composition in the filamentous fungus Penicillium chrysogenum. RESULTS: Methylglyoxal leads to growth rate reduction of this fungus so that the entry into the stationary phase is delayed. Mitochondrial morphology is not changed by methylglyoxal. However, rapamycin-mediated fragmentation of mitochondria is prevented by methylglyoxal. Furthermore, three proteins are identified that are present in lower abundance when methylglyoxal is added to the growth medium (aldo-keto reductase [Pc22g04850], 5-methyl-tetrahydropteroyl triglutamate-homocysteine S-methyltransferase [Pc22g18630] and NAD-dependent formate dehydrogenase [Pc12g04310]). CONCLUSIONS: The presented results contribute to the understanding of cellular pathways and mechanisms that are affected by the ubiquitous alpha-oxoaldehyde methylglyoxal. PMID- 26156310 TI - The "Tree-in-Bud" Pattern on Chest CT: Radiologic and Microbiologic Correlation. AB - BACKGROUND: Tree-in-bud (TIB) is a radiologic pattern seen on high-resolution chest CT reflecting bronchiolar mucoid impaction occasionally with additional involvement of adjacent alveoli. Its microbiologic significance has not been systematically evaluated. OBJECTIVES: We aimed to establish the incidence of the TIB pattern as a proportion of all patients undergoing chest CT and to identify its etiology wherever possible. METHODS: We included all patients with TIB pattern detected on chest CT in our institution from January 2007 to June 2012 and correlated this radiologic finding to the microbiologic etiology, which were available, for each patient. RESULTS: During the study period, TIB pattern was described in 326 patients, which is 1.8% of all chest CTs. Of these, 220 (67.5%) patients had an infectious etiology and 34 (10.4%) had aspiration pneumonia. Other presumptive etiologies were in 13 (4%) lung malignancy, 31 (9.5%) other malignancies, 20 cases (6%) inconclusive etiology or incidental findings, and 8 (2.5%) had other inflammatory disorders. The relative incidence of the various organisms isolated reflected the overall incidence of these bacteria in community or hospital-acquired populations independent of the TIB pattern. No correlation was found between distribution of TIB, the immune status, and the organism isolated. CONCLUSIONS: TIB pattern reflects endobronchiolar inflammation due mainly but not exclusively to an infectious cause. The microbiologic etiology in patients with this finding is similar to that of the general population (community acquired versus hospital acquired). PMID- 26156312 TI - Corrigendum. PMID- 26156311 TI - Transbronchial Catheter Aspiration and Transbronchial Needle Aspiration in the Diagnostic Workup of Peripheral Lung Lesions. AB - PURPOSE: Increasingly frequent, it is clinically indicated to obtain tissue from a peripheral lung lesion (PLL) to yield a pathological diagnosis. The aim of the present study was to evaluate the diagnostic sensitivity of transbronchial needle aspiration (TBNA) and transbronchial catheter aspiration (TBCA) in addition to transbronchial forceps biopsy (TBB) at conventional bronchoscopy. METHODS: Eligible patients showing a PLL on computed tomography scans were included in the study. In all patients, following TBB, TBNA and TBCA were employed in randomised order under fluoroscopy. RESULTS: Fourty-eight patients were enrolled, of whom 46 patients with 46 PLLs were included in the analysis. The mean +/- SD diameter of the PLL was 27.0 +/- 13.3 mm. The overall sensitivity for all modalities was 69.6%; PLL <=20 or >20 and <=30 mm in diameter showed a sensitivity of 60.0 and 72.2%, respectively. For malignant PLL (n = 33), the combined sensitivity of TBNA + TBCA versus TBB was significantly higher (63.6 vs. 33.3%, p <= 0.05), and could not further be improved by TBB. For benign PLL, TBB was superior to TBNA + TBCA (76.9 vs. 38.5%). CONCLUSIONS: TBB, TBNA and TBCA are complementary to one another. Combining the three techniques, even allows transbronchial specimen collection of PLL <3 cm in diameter at conventional bronchoscopy. PMID- 26156314 TI - Development and population dynamics of Steinernema yirgalemense (Rhabditida: Steinernematidae) and growth characteristics of its associated Xenorhabdus indica symbiont in liquid culture. AB - Entomopathogenic nematodes have become a valuable addition to the range of biological control agents available for insect control. An endemic nematode, Steinernema yirgalemense, has been found to be effective against a wide range of key insect pests. The next step would be the mass production this nematode for commercial application. This requires the establishment of monoxenic cultures of both the nematode and the symbiotic bacterium Xenorhabdus indica. First-stage juveniles of S. yirgalemense were obtained from eggs, while X. indica was isolated from nematode-infected wax moth larvae. The population density of the various life stages of S. yirgalemense during the developmental phase in liquid culture was determined. The recovery of infective juveniles (IJs) to the third stage feeding juveniles, was 67 +/- 10%, reaching a maximum population density of 75,000 IJs ml- 1 on day 13 after inoculation. Adult density increased after 8 days, with the maximum female density being 4600 ml- 1 on day 15, whereas the maximum male density was 4300 ml- 1 on day 12. Growth curves for X. indica showed that the exponential phase was reached 15 h after inoculation to the liquid medium. The stationary phase was reached after 42 h, with an average of 51 * 107 colony-forming units ml- 1. Virulence tests showed a significant difference in insect mortality between in vitro- and in vivo-produced nematodes. The success obtained with the production of S. yirgalemense in liquid culture can serve as the first step in the optimizing and upscaling of the commercial production of nematodes in fermenters. PMID- 26156313 TI - Topological characterization of neuronal arbor morphology via sequence representation: I--motif analysis. AB - BACKGROUND: The morphology of neurons offers many insights into developmental processes and signal processing. Numerous reports have focused on metrics at the level of individual branches or whole arbors; however, no studies have attempted to quantify repeated morphological patterns within neuronal trees. We introduce a novel sequential encoding of neurite branching suitable to explore topological patterns. RESULTS: Using all possible branching topologies for comparison we show that the relative abundance of short patterns of up to three bifurcations, together with overall tree size, effectively capture the local branching patterns of neurons. Dendrites and axons display broadly similar topological motifs (over represented patterns) and anti-motifs (under-represented patterns), differing most in their proportions of bifurcations with one terminal branch and in select sub-sequences of three bifurcations. In addition, pyramidal apical dendrites reveal a distinct motif profile. CONCLUSIONS: The quantitative characterization of topological motifs in neuronal arbors provides a thorough description of local features and detailed boundaries for growth mechanisms and hypothesized computational functions. PMID- 26156315 TI - ANN modelling of sediment concentration in the dynamic glacial environment of Gangotri in Himalaya. AB - The present study explores for the first time the possibility of modelling sediment concentration with artificial neural networks (ANNs) at Gangotri, the source of Bhagirathi River in the Himalaya. Discharge, rainfall and temperature have been considered as the main controlling factors of variations in sediment concentration in the dynamic glacial environment of Gangotri. Fourteen feed forward neural networks with error back propagation algorithm have been created, trained and tested for prediction of sediment concentration. Seven models (T1-T7) have been trained and tested in the non-updating mode whereas remaining seven models (T1a-T7a) have been trained in the updating mode. The non-updating mode refers to the scenario where antecedent time (previous time step) values are not used as input to the model. In case of the updating mode, antecedent time values are used as network inputs. The inputs applied in the models are either the variables mentioned above as individual factors (single input networks) or a combination of them (multi-input networks). The suitability of employing antecedent time-step values as network inputs has hence been checked by comparative analysis of model performance in the two modes. The simple feed forward network has been improvised with a series parallel non-linear autoregressive with exogenous input (NARX) architecture wherein true values of sediment concentration have been fed as input during training. In the glacial scenario of Gangotri, maximum sediment movement takes place during the melt period (May-October). Hence, daily data of discharge, rainfall, temperature and sediment concentration for five consecutive melt periods (May-October, 2000-2004) have been used for modelling. High Coefficient of determination values [0.77 0.88] have been obtained between observed and ANN-predicted values of sediment concentration. The study has brought out relationships between variables that are not reflected in normal statistical analysis. A strong rainfall: sediment concentration and temperature: sediment concentration relationship is shown by the models which are not reflected in statistical correlation. It has also been observed that usage of antecedent time-step values as network inputs does not necessarily lead to improvement in model performance. PMID- 26156316 TI - Methods and measurement variance for field estimations of coral colony planar area using underwater photographs and semi-automated image segmentation. AB - Size and growth rates for individual colonies are some of the most essential descriptive parameters for understanding coral communities, which are currently experiencing worldwide declines in health and extent. Accurately measuring coral colony size and changes over multiple years can reveal demographic, growth, or mortality patterns often not apparent from short-term observations and can expose environmental stress responses that may take years to manifest. Describing community size structure can reveal population dynamics patterns, such as periods of failed recruitment or patterns of colony fission, which have implications for the future sustainability of these ecosystems. However, rapidly and non invasively measuring coral colony sizes in situ remains a difficult task, as three-dimensional underwater digital reconstruction methods are currently not practical for large numbers of colonies. Two-dimensional (2D) planar area measurements from projection of underwater photographs are a practical size proxy, although this method presents operational difficulties in obtaining well controlled photographs in the highly rugose environment of the coral reef, and requires extensive time for image processing. Here, we present and test the measurement variance for a method of making rapid planar area estimates of small to medium-sized coral colonies using a lightweight monopod image-framing system and a custom semi-automated image segmentation analysis program. This method demonstrated a coefficient of variation of 2.26% for repeated measurements in realistic ocean conditions, a level of error appropriate for rapid, inexpensive field studies of coral size structure, inferring change in colony size over time, or measuring bleaching or disease extent of large numbers of individual colonies. PMID- 26156317 TI - Ambient air quality and the effects of air pollutants on otolaryngology in Beijing. AB - To investigate temporal patterns, pollution concentrations and the health effects of air pollutants in Beijing we carried out time-series analyses on daily concentrations of ambient air pollutants and daily numbers of outpatient visits for otolaryngology over 2 years (2011-2012) to identify possible health effects of air pollutants. The results showed that PM10 was the major air pollutant in Beijing and that air quality was slightly better in 2012 than in 2011. Seasonal differences were apparent for SO2 and NO2. Both the background and urban areas of Beijing experienced particulate matter pollution in 2011. In addition to local air pollution, Beijing was also affected by pollutants transported from other regions, especially during heavy air pollution episodes. PM10, NO2, and SO2 concentrations showed positive associations with numbers of outpatient visits for otolaryngology during winter. NO2 and SO2 also had adverse ear, nose, and throat health effects outside of winter. The ear, nose, and throat health risks caused by air pollutants were higher during the winter than during the summer. NO2 had stronger influence on increased the likelihood of outpatient visits than SO2. The findings provide additional information about air quality and health effects of air pollution in Beijing. PMID- 26156318 TI - Effect of advanced chronic kidney disease in clinical and echocardiographic outcomes of patients treated with MitraClip system. AB - BACKGROUND: Data regarding the influence of different levels of renal dysfunction on clinical and echocardiographic results of MitraClip therapy are scarce. We aimed to evaluate the impact of baseline advance renal failure in the outcomes of a cohort of patients treated with MitraClip. METHODS AND RESULTS: We analyzed data from a multicenter registry of 173 patients treated with MitraClip between 2009 and 2012. Patients were classified as advanced chronic kidney disease (CKD, creatinine clearance [CrCl] <30 ml/min, group 1, n=20), moderate CKD (CrCl 30-60 ml/min, group 2, n=78) and normal renal function (CrCl >60 ml/min, group 3, n=75). Twenty patients (11.5%) presented advanced CKD. Procedural success was equal in the 3 groups (95.0% group 1, 100% in group 2 and 96.0% in group 3, p=0.180). Post-procedural MR and NYHA class at 1 month (MR >= 3+5.0% vs. 0% vs. 4.0% p=0.190 and NYHA>II 40.0% vs. 21.0% vs. 18.3%, p=0.101) and 6 months (MR >= 3+0% vs. 13.0% vs. 2.7%, p=0.330; and NYHA class>II 54.5% vs. 26.9% vs. 25.6%, p=0.298) did not differ between groups. However, patients in group 1 experienced higher frequency of the composite end-point of mortality or readmission at 16.2 +/- 11.1 months of follow-up (HR 4.8, CI 95% 1.1-21.3). CONCLUSION: Advanced CKD is linked to an excess of cardiac adverse events. This should be judiciously taken into account when selecting patients for MitraClip. PMID- 26156319 TI - The heart and coronary arteries as primary target in severe allergic reactions: Cardiac troponins and the Kounis hypersensitivity-associated acute coronary syndrome. PMID- 26156320 TI - Left ventricular diameters as a reflection of "extreme and mean ratio". PMID- 26156322 TI - The synergic effect of vincristine and vorinostat in leukemia in vitro and in vivo. AB - BACKGROUND: Combination therapy is a key strategy for minimizing drug resistance, a common problem in cancer therapy. The microtubule-depolymerizing agent vincristine is widely used in the treatment of acute leukemia. In order to decrease toxicity and chemoresistance of vincristine, this study will investigate the effects of combination vincristine and vorinostat (suberoylanilide hydroxamic acid (SAHA)), a pan-histone deacetylase inhibitor, on human acute T cell lymphoblastic leukemia cells. METHODS: Cell viability experiments were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle distributions as well as mitochondria membrane potential were analyzed by flow cytometry. In vitro tubulin polymerization assay was used to test tubulin assembly, and immunofluorescence analysis was performed to detect microtubule distribution and morphology. In vivo effect of the combination was evaluated by a MOLT-4 xenograft model. Statistical analysis was assessed by Bonferroni's t test. RESULTS: Cell viability showed that the combination of vincristine and SAHA exhibited greater cytotoxicity with an IC50 value of 0.88 nM, compared to each drug alone, 3.3 and 840 nM. This combination synergically induced G2/M arrest, followed by an increase in cell number at the sub-G1 phase and caspase activation. Moreover, the results of vincristine combined with an HDAC6 inhibitor (tubastatin A), which acetylated alpha-tubulin, were consistent with the effects of vincristine/SAHA co-treatment, thus suggesting that SAHA may alter microtubule dynamics through HDAC6 inhibition. CONCLUSION: These findings indicate that the combination of vincristine and SAHA on T cell leukemic cells resulted in a change in microtubule dynamics contributing to M phase arrest followed by induction of the apoptotic pathway. These data suggest that the combination effect of vincristine/SAHA could have an important preclinical basis for future clinical trial testing. PMID- 26156321 TI - Functional compensation among HMGN variants modulates the DNase I hypersensitive sites at enhancers. AB - DNase I hypersensitive sites (DHSs) are a hallmark of chromatin regions containing regulatory DNA such as enhancers and promoters; however, the factors affecting the establishment and maintenance of these sites are not fully understood. We now show that HMGN1 and HMGN2, nucleosome-binding proteins that are ubiquitously expressed in vertebrate cells, maintain the DHS landscape of mouse embryonic fibroblasts (MEFs) synergistically. Loss of one of these HMGN variants led to a compensatory increase of binding of the remaining variant. Genome-wide mapping of the DHSs in Hmgn1(-/-), Hmgn2(-/-), and Hmgn1(-/-)n2(-/-) MEFs reveals that loss of both, but not a single HMGN variant, leads to significant remodeling of the DHS landscape, especially at enhancer regions marked by H3K4me1 and H3K27ac. Loss of HMGN variants affects the induced expression of stress-responsive genes in MEFs, the transcription profiles of several mouse tissues, and leads to altered phenotypes that are not seen in mice lacking only one variant. We conclude that the compensatory binding of HMGN variants to chromatin maintains the DHS landscape, and the transcription fidelity and is necessary to retain wild-type phenotypes. Our study provides insight into mechanisms that maintain regulatory sites in chromatin and into functional compensation among nucleosome binding architectural proteins. PMID- 26156323 TI - Evidence based community mobilization for dengue prevention in Nicaragua and Mexico (Camino Verde, the Green Way): cluster randomized controlled trial. AB - OBJECTIVE: To test whether community mobilization adds effectiveness to conventional dengue control. DESIGN: Pragmatic open label parallel group cluster randomized controlled trial. Those assessing the outcomes and analyzing the data were blinded to group assignment. Centralized computerized randomization after the baseline study allocated half the sites to intervention, stratified by country, evidence of recent dengue virus infection in children aged 3-9, and vector indices. SETTING: Random sample of communities in Managua, capital of Nicaragua, and three coastal regions in Guerrero State in the south of Mexico. PARTICIPANTS: Residents in a random sample of census enumeration areas across both countries: 75 intervention and 75 control clusters (about 140 households each) were randomized and analyzed (60 clusters in Nicaragua and 90 in Mexico), including 85,182 residents in 18,838 households. INTERVENTIONS: A community mobilization protocol began with community discussion of baseline results. Each intervention cluster adapted the basic intervention-chemical-free prevention of mosquito reproduction-to its own circumstances. All clusters continued the government run dengue control program. MAIN OUTCOME MEASURES: Primary outcomes per protocol were self reported cases of dengue, serological evidence of recent dengue virus infection, and conventional entomological indices (house index: households with larvae or pupae/households examined; container index: containers with larvae or pupae/containers examined; Breteau index: containers with larvae or pupae/households examined; and pupae per person: pupae found/number of residents). Per protocol secondary analysis examined the effect of Camino Verde in the context of temephos use. RESULTS: With cluster as the unit of analysis, serological evidence from intervention sites showed a lower risk of infection with dengue virus in children (relative risk reduction 29.5%, 95% confidence interval 3.8% to 55.3%), fewer reports of dengue illness (24.7%, 1.8% to 51.2%), fewer houses with larvae or pupae among houses visited (house index) (44.1%, 13.6% to 74.7%), fewer containers with larvae or pupae among containers examined (container index) (36.7%, 24.5% to 44.8%), fewer containers with larvae or pupae among houses visited (Breteau index) (35.1%, 16.7% to 55.5%), and fewer pupae per person (51.7%, 36.2% to 76.1%). The numbers needed to treat were 30 (95% confidence interval 20 to 59) for a lower risk of infection in children, 71 (48 to 143) for fewer reports of dengue illness, 17 (14 to 20) for the house index, 37 (35 to 67) for the container index, 10 (6 to 29) for the Breteau index, and 12 (7 to 31) for fewer pupae per person. Secondary per protocol analysis showed no serological evidence of a protective effect of temephos. CONCLUSIONS: Evidence based community mobilization can add effectiveness to dengue vector control. Each site implementing the intervention in its own way has the advantage of local customization and strong community engagement. TRIAL REGISTRATION: ISRCTN27581154. PMID- 26156324 TI - The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma. AB - BACKGROUND: We aimed to evaluate the efficiency and safety of cis/carboplatin plus gemcitabine, which was previously used for mesothelioma but with no recorded proof of its efficiency, compared with cis/carboplatin plus pemetrexed, which is known to be effective in mesothelioma, in comparable historical groups of malignant pleural mesothelioma. METHODS: One hundred and sixteen patients received cis/carboplatin plus pemetrexed (group 1), while 30 patients received cis/carboplatin plus gemcitabine (group 2) between June 1999 and June 2012. The two groups were compared in terms of median survival and adverse events to chemotherapy. RESULTS: The mean ages of groups 1 and 2 were 60.7 and 60.8 years, respectively. Most of the patients (78.1%) had epithelial type tumors, and 47% of the patients had stage IV disease. There was no difference between the two groups in terms of age, gender, asbestos exposure, histology, stage, Karnofsky performance status, presence of pleurodesis, prophylactic radiotherapy, second line chemotherapy and median hemoglobin and serum albumin levels. The median survival time from diagnosis to death or the last day of follow up with a 95% confidence interval was 12 +/- 0.95 months (95% CI: 10.15-13.85) for group 1 and 11.0 +/- 1.09 months (95% CI: 8.85-13.15) for group 2 (Log-Rank: 0.142; p = 0.706). The median survival time from treatment to death or the last day of follow-up with a 95% confidence interval was 11.0 +/- 0.99 months (95% CI: 9.06 12.94) for group 1 and 11.0 +/- 1.52 months (95% CI: 8.02-13.97) for group 2 (Log Rank: 0.584; p = 0.445). The stage and Karnofsky performance status were found to be significant variables on median survival time by univariate analysis. After adjusting for the stage and Karnofsky performance status, the chemotherapy schema was not impressive on median survival time (OR: 0.837; 95% CI: 0.548-1.277; p = 0.409). The progression free survival was 7.0 +/- 0.61 months for group I and 6.0 +/- 1.56 months for group II (Log-Rank: 0.522; p = 0.470). The treatment was generally well tolerated, and the side effects were similar in both groups. CONCLUSIONS: The study indicates that platinum-based gemcitabine is effective and a safe schema in malignant pleural mesothelioma. Further research should include large randomized phase III trials comparing these agents. PMID- 26156326 TI - Next-Generation Sequencing and Immunohistochemistry as Future Gold Standard of ALK Testing in Lung Cancer? PMID- 26156325 TI - Long Noncoding RNA in Digestive Tract Cancers: Function, Mechanism, and Potential Biomarker. AB - Digestive tract cancers (DTCs) are a leading cause of cancer-related death worldwide. Current therapeutic tools for advanced stage DTCs have limitations, and patients with early stage DTCs frequently have a missed diagnosis due to shortage of efficient biomarkers. Consequently, it is necessary to develop novel biomarkers for early diagnosis and novel therapeutic targets for treatment of DTCs. In recent years, long noncoding RNAs (lncRNAs), a class of noncoding RNAs with >200 nucleotides, have been shown to be aberrantly expressed in DTCs and to have an important role in DTC development: the expression profiles of lncRNAs strongly correlated with poor survival of patients with DTCs, and lncRNAs acted as oncogenes or tumor suppressor genes in DTC progression. In this review, we summarized the functional lncRNAs and expounded on their regulatory mechanisms in DTCs. PMID- 26156328 TI - In Reply. PMID- 26156327 TI - Chemoimmunotherapy for Mucosa-Associated Lymphoid Tissue-Type Lymphoma: A Review of the Literature. AB - BACKGROUND: Biological treatments, chemoimmunotherapy, and radiotherapy are associated with excellent disease control in both gastric and extragastric mucosa associated lymphoid tissue (MALT) lymphomas. Systemic treatment approaches with both oral and i.v. agents are being increasingly studied, not only for patients with disseminated MALT lymphoma, but also for those with localized disease. To date, however, recommendations for the use of available systemic modalities have not been clearly defined. MATERIALS AND METHODS: The present report reviews the current data on systemic treatment options for patients with MALT lymphoma and provides recommendations for their use in everyday practice. RESULTS: Different chemotherapeutic agents, including anthracyclines, alkylators, and purine analogs, have been successfully tested in patients with MALT lymphoma. Reducing side effects while maintaining efficacy should be the main goal in treating these indolent lymphomas. From the data from the largest trial performed to date, the combination of chlorambucil plus rituximab (R) appears to be active as first-line treatment. Similarly, R-bendamustine also seems to be highly effective, but a longer follow-up period is needed. R-monotherapy results in lower remission rates, but seems a suitable option for less fit patients. New immunotherapeutic agents such as lenalidomide (with or without rituximab) or clarithromycin show solid activity but have not yet been validated in larger collectives. CONCLUSION: Patients with MALT lymphoma should be treated within prospective trials to further define optimal therapeutic strategies. Systemic treatment is a reasonable option with potentially curative intent in everyday practice. Based on the efficacy and safety data from available studies, the present review provides recommendations for the use of systemic strategies. PMID- 26156329 TI - Therapeutic Effects of Repurposed Therapies in Non-Small Cell Lung Cancer: What Is Old Is New Again. AB - The recent emergence of targeted and immunotherapeutic agents has dramatically changed the management for patients with non-small cell lung cancer (NSCLC). Despite these advances, lung cancer is not exempt from the challenges facing oncology drug development, including the huge financial cost and the time required for drug implementation. Repositioning noncancer therapies with potential antineoplastic properties into new therapeutic niches is an alternative treatment strategy offering the possibility of saving money and time and improving outcomes. The goal of such a strategy is to deliver an effective drug with a favorable toxicity profile at a reduced cost. Preclinical models and observational data have demonstrated promising activity for many of these agents, and they are now being studied in prospective trials. We review the relevant published data regarding the therapeutic effects of metformin, statins, nonsteroidal anti-inflammatory drugs, beta-blockers, and itraconazole in NSCLC, with a focus on the putative mechanisms of action and clinical data. As these drugs are increasingly being tested in clinical trials, we aim to highlight the salient challenges and future strategies to optimize this approach. PMID- 26156330 TI - Steroid-inducible BABY BOOM system for development of fertile Arabidopsis thaliana plants after prolonged tissue culture. AB - KEY MESSAGE: We describe a steroid-inducible BABY BOOM system that improves plant regeneration in Arabidopsis leaf cultures and yields fertile plants. Regeneration of Arabidopsis thaliana plants for extended periods of time in tissue culture may result in sterile plants. We report here a novel approach for A. thaliana regeneration using a regulated system to induce embryogenic cultures from leaf tissue. The system is based on BABY BOOM (BBM), a transcription factor that turns on genes involved in embryogenesis. We transformed the nucleus of A. thaliana plants with BBM:GR, a gene in which the BBM coding region is fused with the glucocorticoid receptor (GR) steroid-binding domain. In the absence of the synthetic steroid dexamethasone (DEX), the BBM:GR fusion protein is localized in the cytoplasm. Only when DEX is included in the culture medium does the BBM transcription factor enter the nucleus and turn on genes involved in embryogenesis. BBM:GR plant lines show prolific shoot regeneration from leaf pieces on media containing DEX. Removal of DEX from the culture media allowed for flowering and seed formation. Therefore, use of BBM:GR leaf tissue for regeneration of plants for extended periods of time in tissue culture will facilitate the recovery of fertile plants. PMID- 26156332 TI - Greatly Enhancing Catalytic Activity of Graphene by Doping the Underlying Metal Substrate. AB - Graphene-based solid-state catalysis represents a new direction in applications of graphene and has attracted a lot of interests recently. However, the difficulty in fine control and large-scale production of previously proposed graphene catalysts greatly limits their industrial applications. Here we present a novel way to enhance the catalytic activity of graphene, which is highly efficient yet easy to fabricate and control. By first-principles calculations, we show that when the underlying metal substrate is doped with impurities, the catalytic activity of the supported graphene can be drastically enhanced. Graphene supported on a Fe/Ni(111) surface is chosen as a model catalyst, and the chemical reaction of CO oxidation is used to probe the catalytic activity of graphene. When the underlying Fe/Ni(111) substrate is impurity free, the graphene is catalytically inactive. When a Zn atom is doped into the substrate, the catalytic activity of the supported graphene is greatly enhanced, and the reaction barrier of the catalyzed CO oxidation is reduced to less than 0.5 eV. Intriguing reaction mechanism of catalyzed CO oxidation is revealed. These studies suggest a new class of graphene-based catalysts and pave the way for future applications of graphene in solid-state catalysis. PMID- 26156331 TI - [Formula: see text]Differences in memory functioning between children with attention-deficit/hyperactivity disorder and/or focal epilepsy. AB - Prior research has shown that attention-deficit/hyperactivity disorder (ADHD) and epilepsy are frequently comorbid and that both disorders are associated with various attention and memory problems. Nonetheless, limited research has been conducted comparing the two disorders in one sample to determine unique versus shared deficits. Hence, we investigated differences in working memory (WM) and short-term and delayed recall between children with ADHD, focal epilepsy of mixed foci, comorbid ADHD/epilepsy and controls. Participants were compared on the Core subtests and the Picture Locations subtest of the Children's Memory Scale (CMS). Results indicated that children with ADHD displayed intact verbal WM and long term memory (LTM), as well as intact performance on most aspects of short-term memory (STM). They performed worse than controls on Numbers Forward and Picture Locations, suggesting problems with focused attention and simple span for visual spatial material. Conversely, children with epilepsy displayed poor focused attention and STM regardless of the modality assessed, which affected encoding into LTM. The only loss over time was found for passages (Stories). WM was intact. Children with comorbid ADHD/epilepsy displayed focused attention and STM/LTM problems consistent with both disorders, having the lowest scores across the four groups. Hence, focused attention and visual-spatial span appear to be affected in both disorders, whereas additional STM/encoding problems are specific to epilepsy. Children with comorbid ADHD/epilepsy have deficits consistent with both disorders, with slight additive effects. This study suggests that attention and memory testing should be a regular part of the evaluation of children with epilepsy and ADHD. PMID- 26156335 TI - A numbers game. PMID- 26156333 TI - Association between the MTHFR A1298C polymorphism and risk of cancer: evidence from 265 case-control studies. AB - Many molecular, epidemiological studies have been performed to explore the association between MTHFR A1298C polymorphism and cancer risk. However, the results were inconsistent or even contradictory. Hence, we performed a meta analysis to investigate the association between cancer risk and MTHFR A1298C (81,040 cases and 114,975 controls from 265 studies) polymorphism. Overall, significant association was observed between MTHFR A1298C polymorphism and cancer risk when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly increased cervical cancer (dominant model: OR 1.46, 95 % CI 1.13-1.90; AC vs. AA: OR 1.48, 95 % CI 1.13 1.92) and lymphoma (dominant model: OR 1.22, 95 % CI 1.04-1.44; recessive model: OR 1.66, 95 % CI 1.15-2.39; CC vs. AA: OR 1.75, 95 % CI 1.21-2.53) risk were observed in Asians, and significantly decreased colorectal cancer risk was found in Asians (recessive model: OR 0.75, 95 % CI 0.59-0.96; CC vs. AA: OR 0.77, 95 % CI 0.60-1.00). In summary, this meta-analysis suggests that MTHFR A1298C polymorphism is associated with increased cervical cancer and lymphoma risk in Asians, and MTHFR A1298C polymorphism is associated with decreased colorectal cancer risk in Asians. Moreover, this meta-analysis also points out the importance of new studies, such as oral cancer and chronic myeloid leukemia, because they had high heterogeneity in this meta-analysis (I (2) > 75 %). PMID- 26156336 TI - The HIV epidemic can be stopped. PMID- 26156334 TI - Occupational Complexity and Cognitive Reserve in a Middle-Aged Cohort at Risk for Alzheimer's Disease. AB - Higher occupational attainment has previously been associated with increased Alzheimer's disease (AD) neuropathology when individuals are matched for cognitive function, indicating occupation could provide cognitive reserve. We examined whether occupational complexity (OCC) associates with decreased hippocampal volume and increased whole-brain atrophy given comparable cognitive function in middle-aged adults at risk for AD. Participants (n = 323) underwent structural MRI, cognitive evaluation, and work history assessment. Three complexity ratings (work with data, people, and things) were obtained, averaged across up to 3 reported jobs, weighted by years per job, and summed to create a composite OCC rating. Greater OCC was associated with decreased hippocampal volume and increased whole-brain atrophy when matched for cognitive function; results remained substantively unchanged after adjusting for several demographic, AD risk, vascular, mental health, and socioeconomic characteristics. These findings suggest that, in people at risk for AD, OCC may confer resilience to the adverse effects of neuropathology on cognition. PMID- 26156337 TI - Cloud cover. PMID- 26156338 TI - We need a measured approach to metrics. PMID- 26156350 TI - Night-time storm chasers stalk their prey on US Plains. PMID- 26156351 TI - European labs set sights on continent-wide computing cloud. PMID- 26156352 TI - Plant denizens get the big-science treatment. PMID- 26156354 TI - Pluto fly-by: a graphical guide to the historic mission. PMID- 26156353 TI - US vaccine researcher sentenced to prison for fraud. PMID- 26156355 TI - The 24/7 search for killer quakes. PMID- 26156356 TI - How to beat HIV. PMID- 26156357 TI - Data analysis: Create a cloud commons. PMID- 26156358 TI - Policy: Development goals should enable decision-making. PMID- 26156362 TI - Carbon statistics: China should come clean on emissions. PMID- 26156363 TI - Commerce: Bolivia set to violate its protected areas. PMID- 26156364 TI - Unwanted mutations: Standards needed for gene-editing errors. PMID- 26156365 TI - Cytokine anniversary: TNF trailblazers five centuries apart. PMID- 26156366 TI - Unpaid researchers: Fieldwork grants would up diversity. PMID- 26156367 TI - Biogeochemistry: Iron's voyage from the abyss. PMID- 26156370 TI - Astrophysics: A twist in the tale of gamma-ray bursts. PMID- 26156368 TI - Biodiversity: Hidden impacts of logging. PMID- 26156371 TI - Feedback in low-mass galaxies in the early Universe. AB - The formation, evolution and death of massive stars release large quantities of energy and momentum into the gas surrounding the sites of star formation. This process, generically termed 'feedback', inhibits further star formation either by removing gas from the galaxy, or by heating it to temperatures that are too high to form new stars. Observations reveal feedback in the form of galactic-scale outflows of gas in galaxies with high rates of star formation, especially in the early Universe. Feedback in faint, low-mass galaxies probably facilitated the escape of ionizing radiation from galaxies when the Universe was about 500 million years old, so that the hydrogen between galaxies changed from neutral to ionized-the last major phase transition in the Universe. PMID- 26156372 TI - A very luminous magnetar-powered supernova associated with an ultra-long gamma ray burst. AB - A new class of ultra-long-duration (more than 10,000 seconds) gamma-ray bursts has recently been suggested. They may originate in the explosion of stars with much larger radii than those producing normal long-duration gamma-ray bursts or in the tidal disruption of a star. No clear supernova has yet been associated with an ultra-long-duration gamma-ray burst. Here we report that a supernova (SN 2011kl) was associated with the ultra-long-duration gamma-ray burst GRB 111209A, at a redshift z of 0.677. This supernova is more than three times more luminous than type Ic supernovae associated with long-duration gamma-ray bursts, and its spectrum is distinctly different. The slope of the continuum resembles those of super-luminous supernovae, but extends further down into the rest-frame ultraviolet implying a low metal content. The light curve evolves much more rapidly than those of super-luminous supernovae. This combination of high luminosity and low metal-line opacity cannot be reconciled with typical type Ic supernovae, but can be reproduced by a model where extra energy is injected by a strongly magnetized neutron star (a magnetar), which has also been proposed as the explanation for super-luminous supernovae. PMID- 26156373 TI - Long-range energy transport in single supramolecular nanofibres at room temperature. AB - Efficient transport of excitation energy over long distances is a key process in light-harvesting systems, as well as in molecular electronics. However, in synthetic disordered organic materials, the exciton diffusion length is typically only around 10 nanometres (refs 4, 5), or about 50 nanometres in exceptional cases, a distance that is largely determined by the probability laws of incoherent exciton hopping. Only for highly ordered organic systems has the transport of excitation energy over macroscopic distances been reported--for example, for triplet excitons in anthracene single crystals at room temperature, as well as along single polydiacetylene chains embedded in their monomer crystalline matrix at cryogenic temperatures (at 10 kelvin, or -263 degrees Celsius). For supramolecular nanostructures, uniaxial long-range transport has not been demonstrated at room temperature. Here we show that individual self assembled nanofibres with molecular-scale diameter efficiently transport singlet excitons at ambient conditions over more than four micrometres, a distance that is limited only by the fibre length. Our data suggest that this remarkable long range transport is predominantly coherent. Such coherent long-range transport is achieved by one-dimensional self-assembly of supramolecular building blocks, based on carbonyl-bridged triarylamines, into well defined H-type aggregates (in which individual monomers are aligned cofacially) with substantial electronic interactions. These findings may facilitate the development of organic nanophotonic devices and quantum information technology. PMID- 26156374 TI - Basin-scale transport of hydrothermal dissolved metals across the South Pacific Ocean. AB - Hydrothermal venting along mid-ocean ridges exerts an important control on the chemical composition of sea water by serving as a major source or sink for a number of trace elements in the ocean. Of these, iron has received considerable attention because of its role as an essential and often limiting nutrient for primary production in regions of the ocean that are of critical importance for the global carbon cycle. It has been thought that most of the dissolved iron discharged by hydrothermal vents is lost from solution close to ridge-axis sources and is thus of limited importance for ocean biogeochemistry. This long standing view is challenged by recent studies which suggest that stabilization of hydrothermal dissolved iron may facilitate its long-range oceanic transport. Such transport has been subsequently inferred from spatially limited oceanographic observations. Here we report data from the US GEOTRACES Eastern Pacific Zonal Transect (EPZT) that demonstrate lateral transport of hydrothermal dissolved iron, manganese, and aluminium from the southern East Pacific Rise (SEPR) several thousand kilometres westward across the South Pacific Ocean. Dissolved iron exhibits nearly conservative (that is, no loss from solution during transport and mixing) behaviour in this hydrothermal plume, implying a greater longevity in the deep ocean than previously assumed. Based on our observations, we estimate a global hydrothermal dissolved iron input of three to four gigamoles per year to the ocean interior, which is more than fourfold higher than previous estimates. Complementary simulations with a global-scale ocean biogeochemical model suggest that the observed transport of hydrothermal dissolved iron requires some means of physicochemical stabilization and indicate that hydrothermally derived iron sustains a large fraction of Southern Ocean export production. PMID- 26156376 TI - Neural fate decisions mediated by combinatorial regulation of Hes1 and miR-9. AB - In the nervous system, Hes1 shows an oscillatory manner in neural progenitors but a persistent one in neurons. Many models involving Hes1 have been provided for the study of neural differentiation but few of them take the role of microRNA into account. It is known that a microRNA, miR-9, plays crucial roles in modulating Hes1 oscillations. However, the roles of miR-9 in controlling Hes1 oscillations and inducing transition between different cell fates still need to be further explored. Here we provide a mathematical model to show the interaction between miR-9 and Hes1, with the aim of understanding how the Hes1 oscillations are produced, how they are controlled, and further, how they are terminated. Based on the experimental findings, the model demonstrates the essential roles of Hes1 and miR-9 in regulating the dynamics of the system. In particular, the model suggests that the balance between miR-9 and Hes1 plays important roles in the choice between progenitor maintenance and neural differentiation. In addition, the synergistic (or antagonistic) effects of several important regulations are investigated so as to elucidate the effects of combinatorial regulation in neural decision-making. Our model provides a qualitative mechanism for understanding the process in neural fate decisions regulated by Hes1 and miR-9. PMID- 26156377 TI - Single centre experience of the application of self navigated 3D whole heart cardiovascular magnetic resonance for the assessment of cardiac anatomy in congenital heart disease. AB - BACKGROUND: For free-breathing cardiovascular magnetic resonance (CMR), the self navigation technique recently emerged, which is expected to deliver high-quality data with a high success rate. The purpose of this study was to test the hypothesis that self-navigated 3D-CMR enables the reliable assessment of cardiovascular anatomy in patients with congenital heart disease (CHD) and to define factors that affect image quality. METHODS: CHD patients >=2 years-old and referred for CMR for initial assessment or for a follow-up study were included to undergo a free-breathing self-navigated 3D CMR at 1.5T. Performance criteria were: correct description of cardiac segmental anatomy, overall image quality, coronary artery visibility, and reproducibility of great vessels diameter measurements. Factors associated with insufficient image quality were identified using multivariate logistic regression. RESULTS: Self-navigated CMR was performed in 105 patients (55% male, 23 +/- 12y). Correct segmental description was achieved in 93% and 96% for observer 1 and 2, respectively. Diagnostic quality was obtained in 90% of examinations, and it increased to 94% if contrast enhanced. Left anterior descending, circumflex, and right coronary arteries were visualized in 93%, 87% and 98%, respectively. Younger age, higher heart rate, lower ejection fraction, and lack of contrast medium were independently associated with reduced image quality. However, a similar rate of diagnostic image quality was obtained in children and adults. CONCLUSION: In patients with CHD, self-navigated free-breathing CMR provides high-resolution 3D visualization of the heart and great vessels with excellent robustness. PMID- 26156378 TI - Enhanced daidzin production from jasmonic and acetyl salicylic acid elicited hairy root cultures of Psoralea corylifolia L. (Fabaceae). AB - Daidzin (7-O-glucoside of daidzein) has several pharmacological benefits in herbal remedy, as antioxidant and shown antidipsotropic activity. Hairy root culture of Psoralea corylifolia L. was developed for biomass and enhanced daidzin production using signalling compounds such as jasmonic acid (JA) and acetyl salicylic acid (ASA). Best response of 2.8-fold daidzin (5.09% DW) with 1 MUM JA treatment after second week and 7.3-fold (3.43% DW) with 10 MUM JA elicitation after 10th week was obtained from hairy roots compared to untreated control. ASA at 10 MUM promoted 1.7-fold increase in daidzin (1.49% DW) content after seventh week compared to control (0.83% DW). Addition of 25 MUM ASA resulted in 1.44% DW daidzin (1.5-fold increase) with 0.91% DW in control after fifth week and 1.44% DW daidzin (2.3-fold increase) after eighth week when compared to untreated control (0.62% DW). Reduced biomass with increased daidzin content was facilitated by elicited hairy root cultures. PMID- 26156379 TI - Adaptive categorization of sound frequency does not require the auditory cortex in rats. AB - A defining feature of adaptive behavior is our ability to change the way we interpret sensory stimuli depending on context. Rapid adaptation in behavior has been attributed to frontal cortical circuits, but it is not clear if sensory cortexes also play an essential role in such tasks. In this study we tested whether the auditory cortex was necessary for rapid adaptation in the interpretation of sounds. We used a two-alternative choice sound-categorization task for rats in which the boundary that separated two acoustic categories changed several times within a behavioral session. These shifts in the boundary resulted in changes in the rewarded action for a subset of stimuli. We found that extensive lesions of the auditory cortex did not impair the ability of rats to switch between categorization contingencies and sound discrimination performance was minimally impaired. Similar results were obtained after reversible inactivation of the auditory cortex with muscimol. In contrast, lesions of the auditory thalamus largely impaired discrimination performance and, as a result, the ability to modify behavior across contingencies. Thalamic lesions did not impair performance of a visual discrimination task, indicating that the effects were specific to audition and not to motor preparation or execution. These results suggest that subcortical outputs of the auditory thalamus can mediate rapid adaptation in the interpretation of sounds. PMID- 26156380 TI - Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation. AB - Gain-of-function missense mutations in voltage-gated sodium channel Nav1.7 have been linked to small-fiber neuropathy, which is characterized by burning pain, dysautonomia and a loss of intraepidermal nerve fibers. However, the mechanistic cascades linking Nav1.7 mutations to axonal degeneration are incompletely understood. The G856D mutation in Nav1.7 produces robust changes in channel biophysical properties, including hyperpolarized activation, depolarized inactivation, and enhanced ramp and persistent currents, which contribute to the hyperexcitability exhibited by neurons containing Nav1.8. We report here that cell bodies and neurites of dorsal root ganglion (DRG) neurons transfected with G856D display increased levels of intracellular Na(+) concentration ([Na(+)]) and intracellular [Ca(2+)] following stimulation with high [K(+)] compared with wild type (WT) Nav1.7-expressing neurons. Blockade of reverse mode of the sodium/calcium exchanger (NCX) or of sodium channels attenuates [Ca(2+)] transients evoked by high [K(+)] in G856D-expressing DRG cell bodies and neurites. We also show that treatment of WT or G856D-expressing neurites with high [K(+)] or 2-deoxyglucose (2-DG) does not elicit degeneration of these neurites, but that high [K(+)] and 2-DG in combination evokes degeneration of G856D neurites but not WT neurites. Our results also demonstrate that 0 Ca(2+) or blockade of reverse mode of NCX protects G856D-expressing neurites from degeneration when exposed to high [K(+)] and 2-DG. These results point to [Na(+)] overload in DRG neurons expressing mutant G856D Nav1.7, which triggers reverse mode of NCX and contributes to Ca(2+) toxicity, and suggest subtype-specific blockade of Nav1.7 or inhibition of reverse NCX as strategies that might slow or prevent axon degeneration in small-fiber neuropathy. PMID- 26156381 TI - Generalization and transfer of contextual cues in motor learning. AB - We continuously adapt our movements in daily life, forming new internal models whenever necessary and updating existing ones. Recent work has suggested that this flexibility is enabled via sensorimotor cues, serving to access the correct internal model whenever necessary and keeping new models apart from previous ones. While research to date has mainly focused on identifying the nature of such cue representations, here we investigated whether and how these cue representations generalize, interfere, and transfer within and across effector systems. Subjects were trained to make two-stage reaching movements: a premovement that served as a cue, followed by a targeted movement that was perturbed by one of two opposite curl force fields. The direction of the premovement was uniquely coupled to the direction of the ensuing force field, enabling simultaneous learning of the two respective internal models. After training, generalization of the two premovement cues' representations was tested at untrained premovement directions, within both the trained and untrained hand. We show that the individual premovement representations generalize in a Gaussian like pattern around the trained premovement direction. When the force fields are of unequal strengths, the cue-dependent generalization skews toward the strongest field. Furthermore, generalization patterns transfer to the nontrained hand, in an extrinsic reference frame. We conclude that contextual cues do not serve as discrete switches between multiple internal models. Instead, their generalization suggests a weighted contribution of the associated internal models based on the angular separation from the trained cues to the net motor output. PMID- 26156382 TI - Spatial variation of compound muscle action potentials across human gastrocnemius medialis. AB - The massed action potential (M wave) elicited through nerve stimulation underpins a wide range of physiological and mechanical understanding of skeletal muscle structure and function. Although systematic approaches have evaluated the effect of different factors on M waves, the effect of the location and distribution of activated fibers within the muscle remains unknown. By detecting M waves from the medial gastrocnemius (MG) of 12 participants with a grid of 128 electrodes, we investigated whether different populations of muscle units have different spatial organization within MG. If populations of muscle units occupy discrete MG regions, current pulses of progressively greater intensities applied to the MG nerve branch would be expected to lead to local changes in M-wave amplitudes. Electrical pulses were therefore delivered at 2 pps, with the current pulse amplitude increased every 10 stimuli to elicit different degrees of muscle activation. The localization of MG response to increases in current intensity was determined from the spatial distribution of M-wave amplitude. Key results revealed that increases in M-wave amplitude were detected somewhat locally, by 10 50% of the 128 electrodes. Most importantly, the electrodes detecting greatest increases in M-wave amplitude were localized at different regions in the grid, with a tendency for greater stimulation intensities to elicit M waves in the more distal MG region. The presented results indicate that M waves recorded locally may not provide a representative MG response, with major implications for the estimation of, e.g., the maximal stimulation levels, the number of motor units, and the onset and normalization in H-reflex studies. PMID- 26156383 TI - Twitch-related and rhythmic activation of the developing cerebellar cortex. AB - The cerebellum is a critical sensorimotor structure that exhibits protracted postnatal development in mammals. Many aspects of cerebellar circuit development are activity dependent, but little is known about the nature and sources of the activity. Based on previous findings in 6-day-old rats, we proposed that myoclonic twitches, the spontaneous movements that occur exclusively during active sleep (AS), provide generalized as well as topographically precise activity to the developing cerebellum. Taking advantage of known stages of cerebellar cortical development, we examined the relationship between Purkinje cell activity (including complex and simple spikes), nuchal and hindlimb EMG activity, and behavioral state in unanesthetized 4-, 8-, and 12-day-old rats. AS dependent increases in complex and simple spike activity peaked at 8 days of age, with 60% of units exhibiting significantly more activity during AS than wakefulness. Also, at all three ages, approximately one-third of complex and simple spikes significantly increased their activity within 100 ms of twitches in one of the two muscles from which we recorded. Finally, we observed rhythmicity of complex and simple spikes that was especially prominent at 8 days of age and was greatly diminished by 12 days of age, likely due to developmental changes in climbing fiber and mossy fiber innervation patterns. All together, these results indicate that the neurophysiological activity of the developing cerebellum can be used to make inferences about changes in its microcircuitry. They also support the hypothesis that sleep-related twitches are a prominent source of discrete climbing and mossy fiber activity that could contribute to the activity-dependent development of this critical sensorimotor structure. PMID- 26156384 TI - Diabetic hyperglycemia reduces Ca2+ permeability of extrasynaptic AMPA receptors in AII amacrine cells. AB - There is increasing evidence that diabetic retinopathy is a primary neuropathological disorder that precedes the microvascular pathology associated with later stages of the disease. Recently, we found evidence for altered functional properties of synaptic alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) receptors in A17, but not AII, amacrine cells in the mammalian retina, and the observed changes were consistent with an upregulation of the GluA2 subunit, a key determinant of functional properties of AMPA receptors, including Ca(2+) permeability and current-voltage (I-V) rectification properties. Here, we have investigated functional changes of extrasynaptic AMPA receptors in AII amacrine cells evoked by diabetes. With patch clamp recording of nucleated patches from retinal slices, we measured Ca(2+) permeability and I-V rectification in rats with ~3 wk of streptozotocin-induced diabetes and age-matched, noninjected controls. Under bi-ionic conditions (extracellular Ca(2+) concentration = 30 mM, intracellular Cs(+) concentration = 171 mM), the reversal potential (Erev) of AMPA-evoked currents indicated a significant reduction of Ca(2+) permeability in diabetic animals [Erev = -17.7 mV, relative permeability of Ca(2+) compared with Cs(+) (PCa/PCs) = 1.39] compared with normal animals (Erev = -7.7 mV, PCa/PCs = 2.35). Insulin treatment prevented the reduction of Ca(2+) permeability. I-V rectification was examined by calculating a rectification index (RI) as the ratio of the AMPA-evoked conductance at +40 and -60 mV. The degree of inward rectification in patches from diabetic animals (RI = 0.48) was significantly reduced compared with that in normal animals (RI = 0.30). These results suggest that diabetes evokes a change in the functional properties of extrasynaptic AMPA receptors of AII amacrine cells. These changes could be representative for extrasynaptic AMPA receptors elsewhere in AII amacrine cells and suggest that synaptic and extrasynaptic AMPA receptors are differentially regulated. PMID- 26156385 TI - Functional segregation of voltage-activated calcium channels in motoneurons of the dorsal motor nucleus of the vagus. AB - Calcium influx elevates mitochondrial oxidant stress (mOS) in dorsal motor nucleus of the vagus (DMV) neurons that are prone to Lewy body pathologies in presymptomatic Parkinson's disease (PD) patients. In experimental PD models, treatment with isradipine, the dihydropyridine with the highest affinity to Cav1.3 channels, prevents subthreshold calcium influx via Cav1.3 channels into midbrain dopamine neurons and protects them from mOS. In DMV neurons, isradipine is also effective in reducing mOS despite overwhelming evidence that subthreshold calcium influx is negligible compared with spike-triggered influx. To solve this conundrum we combined slice electrophysiology, two-photon laser scanning microscopy, mRNA profiling, and computational modeling. We find that the unusually depolarized subthreshold voltage trajectory of DMV neurons is positioned between the relatively hyperpolarized activation curve of Cav1.3 channels and that of other high-voltage activated (HVA) calcium channels, thus creating a functional segregation between Cav1.3 and HVA calcium channels. The HVA channels flux the bulk of calcium during spikes but can only influence pacemaking through their coupling to calcium-activated potassium currents. In contrast, Cav1.3 currents, which we show to be more than an order-of-magnitude smaller than the HVA calcium currents, are able to introduce sufficient inward current to speed up firing. However, Kv4 channels that are constitutively open in the subthreshold range guarantee slow pacemaking, despite the depolarizing action of Cav1.3 and other pacemaking currents. We propose that the efficacy of isradipine in preventing mOS in DMV neurons arises from its mixed effect on Cav1.3 channels and on HVA Cav1.2 channels. PMID- 26156386 TI - Locomotor adaptation is modulated by observing the actions of others. AB - Observing the motor actions of another person could facilitate compensatory motor behavior in the passive observer. Here we explored whether action observation alone can induce automatic locomotor adaptation in humans. To explore this possibility, we used the "broken escalator" paradigm. Conventionally this involves stepping upon a stationary sled after having previously experienced it actually moving (Moving trials). This history of motion produces a locomotor aftereffect when subsequently stepping onto a stationary sled. We found that viewing an actor perform the Moving trials was sufficient to generate a locomotor aftereffect in the observer, the size of which was significantly correlated with the size of the movement (postural sway) observed. Crucially, the effect is specific to watching the task being performed, as no motor adaptation occurs after simply viewing the sled move in isolation. These findings demonstrate that locomotor adaptation in humans can be driven purely by action observation, with the brain adapting motor plans in response to the size of the observed individual's motion. This mechanism may be mediated by a mirror neuron system that automatically adapts behavior to minimize movement errors and improve motor skills through social cues, although further neurophysiological studies are required to support this theory. These data suggest that merely observing the gait of another person in a challenging environment is sufficient to generate appropriate postural countermeasures, implying the existence of an automatic mechanism for adapting locomotor behavior. PMID- 26156387 TI - Effect of mechanical tactile noise on amplitude of visual evoked potentials: multisensory stochastic resonance. AB - The present investigation documents the electrophysiological occurrence of multisensory stochastic resonance in the human visual pathway elicited by tactile noise. We define multisensory stochastic resonance of brain evoked potentials as the phenomenon in which an intermediate level of input noise of one sensory modality enhances the brain evoked response of another sensory modality. Here we examined this phenomenon in visual evoked potentials (VEPs) modulated by the addition of tactile noise. Specifically, we examined whether a particular level of mechanical Gaussian noise applied to the index finger can improve the amplitude of the VEP. We compared the amplitude of the positive P100 VEP component between zero noise (ZN), optimal noise (ON), and high mechanical noise (HN). The data disclosed an inverted U-like graph for all the subjects, thus demonstrating the occurrence of a multisensory stochastic resonance in the P100 VEP. PMID- 26156388 TI - Consequences of acute and long-term removal of neuromodulatory input on the episodic gastric rhythm of the crab Cancer borealis. AB - For decades, the episodic gastric rhythm of the crustacean stomatogastric nervous system (STNS) has served as an important model system for understanding the generation of rhythmic motor behaviors. Here we quantitatively describe many features of the gastric rhythm of the crab Cancer borealis under several conditions. First, we analyzed spontaneous gastric rhythms produced by freshly dissected preparations of the STNS, including the cycle frequency and phase relationships among gastric units. We find that phase is relatively conserved across frequency, similar to the pyloric rhythm. We also describe relationships between these two rhythms, including a significant gastric/pyloric frequency correlation. We then performed continuous, days-long extracellular recordings of gastric activity from preparations of the STNS in which neuromodulatory inputs to the stomatogastric ganglion were left intact and also from preparations in which these modulatory inputs were cut (decentralization). This allowed us to provide quantitative descriptions of variability and phase conservation within preparations across time. For intact preparations, gastric activity was more variable than pyloric activity but remained relatively stable across 4-6 days, and many significant correlations were found between phase and frequency within animals. Decentralized preparations displayed fewer episodes of gastric activity, with altered phase relationships, lower frequencies, and reduced coordination both among gastric units and between the gastric and pyloric rhythms. Together, these results provide insight into the role of neuromodulation in episodic pattern generation and the extent of animal-to-animal variability in features of spontaneously occurring gastric rhythms. PMID- 26156390 TI - Unusual domain movement in a multidomain protein in the presence of macromolecular crowders. AB - Domain movements play a fundamental and critical role in the specific biological function that multidomain proteins have evolved to perform. A significant amount of research has been carried out to investigate the effects of macromolecular crowding agents, mostly on single domain proteins, thereby furthering our appreciation for the crowding phenomenon. However similar studies on proteins having multiple domains are relatively scarce. Using the plasma protein human serum albumin (HSA) as the protein of interest, we have probed the influence of dextran based crowding agents (Dextran 6, Dextran 40, and Dextran 70) on the relative movements of domains I and II using FRET, with Trp-214 in domain II acting as the donor and acrylodan (Ac) covalently attached to Cys-34 of domain I as the acceptor. Amongst the higher molecular weight crowders, while both Dextran 70 and Dextran 40 induced a significant decrease in the distance between the aforesaid domains, however for the latter macromolecular crowder (Dextran 40), beyond 50 g L(-1), no change in domain separation was observed even up to concentrations of 175 g L(-1). On the other hand, contrary to our expectations, Dextran 6, having the highest packing density by virtue of it being the smallest crowding agent used, provided an asymmetric excluded volume which resulted in forced elongation of HSA along the Trp-Ac FRET axis. Additionally both chemical and thermal studies performed at varying concentrations of the chemical denaturant, urea, reveal unusual movements of the two domains, an aspect that can have important implications with regard to HSA being an avid transporter of fatty acids, with the binding of latter being known to invoke appreciable domain displacements. We hypothesise that we see a distinct crossover from entropy dominated depletion effects in the case of Dextran 6 to significant enthalpic contribution for Dextran 70 with Dextran 40 lying midway between these two crowders, having characteristics of both. PMID- 26156389 TI - An MRI-based feasibility study of unilateral percutaneous vertebroplasty. AB - BACKGROUND: Percutaneous vertebroplasty (PVP) has been demonstrated to be effective in the treatment of osteoporotic fracture. The bilateral pedicular approach is the most frequently used method. However, unilateral PVP is becoming increasingly more attractive for surgeons because of its numerous benefits, including lower radiation exposure, less tissue injury, and less bone cement leakage. The purpose of this study was to investigate the anatomical feasibility of unilateral PVP by exploring the differences in the puncture success rate of the unilateral pedicular approach among different lumbar segments, between men and women, and between the left and right sides. METHODS: Punctures were simulated on magnetic resonance imaging scans of 200 patients (100 men, 100 women) at a maximum angle via a pedicular approach. The distance between the entry point and the midline of the vertebral body, the maximum puncture angle, the puncture success value, and the puncture success rate were measured and compared among different lumbar levels, between the two sexes, and between the left and right sides. RESULTS: The maximum puncture distance between the entry point and the midline gradually increased from L1 to L5, and the maximum puncture angle showed the same tendency from L1 to L5. The puncture success values for L3 and L4 were higher than those for the other lumbar levels (L1, 31.53 +/- 34.45; L2, 42.15 +/- 28.06; L3, 56.21 +/- 18.30; L4, 56.20 +/- 12.93; and L5, 48.01 +/- 6.88). The puncture success rates varied from 69.5 to 98.0 % among the different lumbar levels; L3 and L4 were the two highest (L3, 95.5 %; L4, 98.0 %). There were significant differences in these measurements between men and women and between the left and right sides. CONCLUSIONS: PVP with the unilateral puncture approach appears more likely to succeed at L3 to L5 than at L1 and L2. The unilateral approach might be more suitable for men than women at levels other than L5. Additionally, the left pedicular approach might be optimal for unilateral PVP procedures. PMID- 26156391 TI - Management of prehospital shoulder dislocation: feasibility and need of reduction. AB - PURPOSE: Dislocation of the shoulder is rare in the prehospital setting. The medical specialities of the emergency physicians are heterogeneous, and the level of experience is different. Aim of this study was to evaluate the feasibility, sufficiency, and need of prehospital reduction. METHODS: Over 12 months, 16 rescue stations in Germany and Austria documented cases. Points of examination were: incidence of reduction, influence of pathological findings, therapy and effectiveness of reduction. RESULTS: We included 70 patients. A reduction was undertaken in n = 47 (66.6 %). In n = 70 (100 %) perfusion was without pathological finding after reduction, all n = 7 (10 %) neurological pathologies declined after reduction. There was no significance in total implementation of prehospital reduction between surgeons and anaesthetists. N = 63 (90 %) of all patients received an immobilisation of the shoulder. N = 68 (97 %) of all patients were transported to a hospital. Time to arrival in hospital was in n = 50 (71.4 %) <=10 min, in n = 17 (24.2 %) <=20 min and in n = 3 (4.4 %) <=30 min. CONCLUSION: Implementation of reduction is independent of pathological neurological or vascular findings. Knowledge and skill is enough to perform a reduction quiet effectively in all emergency physicians. No specific technique can be recommended for prehospital use, the importance of being skilled is more important than one method. Early reduction was performed most rapidly in surgeons, but as well in the recommended time by other medical disciplines. On documented timings to admission hospital waiver of reduction is doubt. Therefore, a reduction in the prehospital setting is possible, but not obligatory. PMID- 26156393 TI - CpG site DNA methylation of the CCAAT/enhancer-binding protein, alpha promoter in chicken lines divergently selected for fatness. AB - CCAAT/enhancer-binding protein (C/EBP), alpha (CEBPA) is a master regulator of adipogenesis and, together with peroxisome proliferator-activated receptor gamma (PPARG), plays a critical role in adipocyte differentiation. Previous studies have demonstrated that CEBPA is regulated by DNA methylation and involved in the osteogenesis and adipogenesis of mouse C3H10T1/2 and bone marrow stromal cells. However, it is unclear whether CEBPA is regulated by DNA methylation in adipose tissues. Thus, the objectives of the present study were to investigate CpG site methylation in a 357-bp CEBPA promoter region and to assess the correlation between promoter CpG site methylation and CEBPA gene expression in the abdominal adipose tissues of Northeast Agricultural University broiler lines divergently selected for abdominal fat content. The results showed that the methylation percentage of the analyzed CEBPA promoter region was significantly higher in lean broilers than in fat broilers at 2 weeks (80.3% vs. 43.4%, P < 0.0001), 3 weeks (95.4% vs. 74.0%, P < 0.0001) and 7 weeks of age (82.6% vs. 57.2%, P < 0.0001). Real-time quantitative RT-PCR analysis showed that CEBPA expression was significantly higher in the fat vs. the lean line at 2 weeks of age (P = 0.0013) but not at 3 or 7 weeks of age. The correlation analysis showed that only at 2 weeks of age was the methylation percentage negatively correlated with CEBPA expression (Pearson's r = -0.8312, P = 0.0029). Of all seven tested CpGs, only two, the CpGs at -1494 and -1478 bp, displayed a significantly negative correlation with CEBPA mRNA expression. These results suggest that the CEBPA is methylated in adipose tissue and may regulate chicken early adipose development. PMID- 26156394 TI - Preclinical Development of an Anti-NaPi2b (SLC34A2) Antibody-Drug Conjugate as a Therapeutic for Non-Small Cell Lung and Ovarian Cancers. AB - PURPOSE: Antibody-drug conjugates (ADC) selectively deliver a cytotoxic drug to cells expressing an accessible antigenic target. Here, we have appended monomethyl auristatin E (MMAE) to an antibody recognizing the SLC34A2 gene product NaPi2b, the type II sodium-phosphate cotransporter, which is highly expressed on tumor surfaces of the lung, ovary, and thyroid as well as on normal lung pneumocytes. This study evaluated its efficacy and safety in preclinical studies. EXPERIMENTAL DESIGN: The efficacy of anti-NaPi2b ADC was evaluated in mouse ovarian and non-small cell lung cancer (NSCLC) tumor xenograft models, and its toxicity was assessed in rats and cynomolgus monkeys. RESULTS: We show here that an anti-NaPi2b ADC is effective in mouse ovarian and NSCLC tumor xenograft models and well-tolerated in rats and cynomolgus monkeys at levels in excess of therapeutic doses. Despite high levels of expression in normal lung of non-human primate, the cross-reactive ADC exhibited an acceptable safety profile with a dose-limiting toxicity unrelated to normal tissue target expression. The nonproliferative nature of normal pneumocytes, together with the antiproliferative mechanism of MMAE, likely mitigates the potential liability of this normal tissue expression. CONCLUSIONS: Overall, our preclinical results suggest that the ADC targeting NaPi2b provides an effective new therapy for the treatment of NSCLC and ovarian cancer and is currently undergoing clinical developments. PMID- 26156396 TI - Metabolic faecal fingerprinting of trans-resveratrol and quercetin following a high-fat sucrose dietary model using liquid chromatography coupled to high resolution mass spectrometry. AB - Faecal non-targeted metabolomics deciphers metabolic end-products resulting from the interactions among food, host genetics, and gut microbiota. Faeces from Wistar rats fed a high-fat sucrose (HFS) diet supplemented with trans-resveratrol and quercetin (separately or combined) were analysed by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Metabolomics in faeces are categorised into four clusters based on the type of treatment. Tentative identification of significantly differing metabolites highlighted the presence of carbohydrate derivatives or conjugates (3-phenylpropyl glucosinolate and dTDP-D mycaminose) in the quercetin group. The trans-resveratrol group was differentiated by compounds related to nucleotides (uridine monophosphate and 2,4 dioxotetrahydropyrimidine D-ribonucleotide). Marked associations between bacterial species (Clostridium genus) and the amount of some metabolites were identified. Moreover, trans-resveratrol and resveratrol-derived microbial metabolites (dihydroresveratrol and lunularin) were also identified. Accordingly, this study confirms the usefulness of omics-based techniques to discriminate individuals depending on the physiological effect of food constituents and represents an interesting tool to assess the impact of future personalized therapies. PMID- 26156395 TI - NEDD8 Inhibition Overcomes CKS1B-Induced Drug Resistance by Upregulation of p21 in Multiple Myeloma. AB - PURPOSE: CKS1B is significantly upregulated in multiple myeloma and associated with poor prognosis. The identification of novel therapies is essential for effective treatment of patients resistant to chemotherapy. The NEDD8 inhibitor MLN4924 selectively targets SCF(Skp2) activation and offers a more specific approach to protein degradation inhibition than total proteasomal inhibition. The goal of this study was to evaluate whether MLN4924 is effective in high CKS1B conditions and identify mechanisms regulating drug potency. EXPERIMENTAL DESIGN: Bortezomib and MLN4924 sensitivity was assessed through proliferation, viability, clonogenic potential, and senescence induction in cells overexpressing CKS1B. The mechanism for MLN4924 sensitivity was elucidated by immunoblot analysis of SCF(skp) substrates and confirmed by shRNA knockdown. The clinical relevance of the NEDD8 pathway was examined in gene expression profiles (GEP) derived from healthy people, patients with monoclonal gammopathy of undetermined significance (MGUS), and multiple myeloma. RESULTS: Cells overexpressing CKS1B were resistant to bortezomib but sensitive to MLN4924. Treatment of CKS1B-overexpressing cells with MLN4924 decreased proliferation, clonogenicity, and induced senescence. MLN4924, but not bortezomib, induced stabilization of p21 and knockdown of p21 resulted in loss of MLN4924 sensitivity. Patients with MGUS and multiple myeloma exhibited increased expression of NEDD8 pathway genes relative to normal plasma cells. Multiple myeloma patients with high NEDD8 expression were linked to bortezomib resistance in clinical trials, and had inferior outcomes. CONCLUSIONS: Our data demonstrate that cells with elevated CKS1B expression are resistant to bortezomib but sensitive to MLN4924 and offer a mechanism through the stabilization of p21. These findings provide rationale for targeting the NEDD8 pathway in multiple myeloma patients exhibiting elevated expression of CKS1B. Clin Cancer Res; 21(24); 5532-42. (c)2015 AACR. PMID- 26156397 TI - Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study. AB - BACKGROUND: Glioblastoma (GBM) is a highly invasive, aggressive, and incurable brain tumor. Genetic factors play important roles in GBM risk. The aim of this study was to elucidate the influence of gene polymorphism on GBM susceptibility. MATERIAL AND METHODS: In this case-control study, we included 72 GBM patients and 320 healthy controls to analyze the association between 29 single-nucleotide polymorphisms and GBM cancer risk in the Chinese Han population. The single nucleotide polymorphisms were determined by Sequenom MassARRAY RS1000 and statistical analysis was performed using SPSS software and SNPStats software. RESULTS: Using the chi(2) test, we found that rs2297440 and rs6010620 in RTEL1 increased risk of GBM. In the recessive model, we also found that the genotypes "CC" of rs2297440 and "GG" of rs6010620 in RTEL1 significantly increased GBM risk. The variant TT genotype of TREH rs17748 and the variant TT genotype of PHLDB1 rs498872 decreased GBM risk in the recessive model. We also found that the TREH rs17748 variant C allele showed an increased risk in males in the dominant model. CONCLUSIONS: Our results suggest a significant association between the RETL1, TREH, and PHLDB1 genes and GBM development in the Han Chinese population. PMID- 26156399 TI - Health Information Technology: An Expanded Care Coordination in Rural Tennessee. AB - The Expanded Care Coordination through the Use of Health Information Technology in Rural Tennessee was a 3-year initiative implemented by The University of Tennessee Children's Mental Health Services Research Center and the Helen Ross McNabb Center Regional Mental Health System. The program targeted rural adults in the East Tennessee area. This intervention utilized the Alcohol Use Disorder Identification Test (AUDIT), Drug Abuse Screening Test (DAST), and AC-COD screening tools. After the initial screening, the appropriate level of intervention was assessed. Clients completed modules on the program's website and met with a clinician for a minimum for four face-to-face meetings. Alcohol use and drug use declined significantly over the course of the program. Alcohol use and outpatient treatment for alcohol and substance abuse declined significantly over the course of the program. There were also significant decreases in days of probations, depression, physical complaints, and violent behaviors. Health information technology is becoming more common in mental health treatment facilities. However, more testing needs to be done with larger samples to assess the efficacy of the program. PMID- 26156398 TI - Does Triatoma brasiliensis occupy the same environmental niche space as Triatoma melanica? AB - BACKGROUND: Triatomines (Hemiptera, Reduviidae) are vectors of Trypanosoma cruzi, the causative agent of Chagas disease, one of the most important vector-borne diseases in Latin America. This study compares the environmental niche spaces of Triatoma brasiliensis and Triatoma melanica using ecological niche modelling and reports findings on DNA barcoding and wing geometric morphometrics as tools for the identification of these species. METHODS: We compared the geographic distribution of the species using generalized linear models fitted to elevation and current data on land surface temperature, vegetation cover and rainfall recorded by earth observation satellites for northeastern Brazil. Additionally, we evaluated nucleotide sequence data from the barcode region of the mitochondrial cytochrome c oxidase subunit I (CO1) and wing geometric morphometrics as taxonomic identification tools for T. brasiliensis and T. melanica. RESULTS: The ecological niche models show that the environmental spaces currently occupied by T. brasiliensis and T. melanica are similar although not equivalent, and associated with the caatinga ecosystem. The CO1 sequence analyses based on pair wise genetic distance matrix calculated using Kimura 2-Parameter (K2P) evolutionary model, clearly separate the two species, supporting the barcoding gap. Wing size and shape analyses based on seven landmarks of 72 field specimens confirmed consistent differences between T. brasiliensis and T. melanica. CONCLUSION: Our results suggest that the separation of the two species should be attributed to a factor that does not include the current environmental conditions. However, as the caatinga is a biome that has existed in the area for at least the last 18,000 years, past conditions might have had an influence in the speciation process. The DNA Barcoding approach may be extended to these members of the subfamily Triatominae. PMID- 26156400 TI - Teens and Preventive Care Use: Implications for EPSDT Outreach. AB - Teens have low overall preventive care utilization compared to other age groups. Low health care use by teens is a result of a variety of complex economic, social, and cultural factors. This study, completed by one local community health board responsible for the administration of the Early Periodic Screening Diagnosis and Treatment (EPSDT) program, produced findings that enhanced outreach to teens and supported the medical providers who serve them. More than 800 teens and young adults from a variety of cultures and communities across an urban Minnesota county were surveyed to understand the conditions under which they do and do not seek medical care. Findings suggest teens with structural barriers associated with poverty such as lack of insurance and transportation to clinics could benefit from intentional connections to medical programs. Psychosocial barriers, revolving around trust, relationships with providers, communication, and privacy, might be ameliorated through enhanced education and targeted outreach to clinics and teens, activities appropriate under the objectives and program activities of EPSDT. This study could be replicated in any community to gather data unique to local populations being served. PMID- 26156401 TI - Behavioral Health Providers for Persons Who Are Deaf, Deafblind, or Hard-of Hearing: A National Survey of the Structural and Process Domains of Care. AB - Research suggests higher prevalence of mental health problems for those with hearing problems than in the general population. Despite barriers, mental health services for persons who are deaf and hard-of-hearing (HOH) have developed to meet the cultural and communication needs of this population. The authors conducted a national survey of mental health service providers to persons who are deaf, deafblind, or HOH, to learn about their structural and process domains of care. Results indicate that services for persons who are deaf, deafblind, or HOH are inadequate for consumers with serious mental illness. Results also uncovered unique pathways to care and practitioners. PMID- 26156402 TI - Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal fibrosis compared with Th1-biased T-bet and Th17-biased RORgammat transgenic mice. AB - Encapsulating peritoneal sclerosis is one of the most serious complications of long-term peritoneal dialysis. The pathogenesis of encapsulating peritoneal sclerosis has not been elucidated, but several putative factors necessary for the development of peritoneum fibrosis (PF) have been reported. However, the roles of T helper (Th) cells in the progression of PF are unknown. The purpose of this study was to clarify the roles of Th1, Th2, and Th17 cells in the progression of PF. T-bet, GATA-3, and RORgammat are Th1, Th2, and Th17 lineage commitment transcription factors, respectively. We previously generated Th1-biased (T-bet transgenic (Tg)) mice, Th2-biased (GATA-3 Tg) mice, and Th17-biased (RORgammat Tg) mice. In this study, Th1, Th2, Th17-biased, and wild-type mice were administered chlorhexidine gluconate (CG) intraperitoneally and analyzed on day 21. CG-injected GATA-3 Tg mice showed a distended intestinal tract and developed marked thickening of the submesothelial space compared with the other groups. CG injected GATA-3 Tg mice also showed significant expression of alpha-SMA positive cells, macrophages, and collagen III in the submesothelium. In contrast, CG injected T-bet Tg mice only developed mild peritoneal fibrosis. Cytokines analysis in peritoneal fluid showed that IFN-gamma was significantly increased in CG-injected T-bet Tg mice and that IL-13 was significantly increased in CG injected GATA-3 Tg mice. Moreover, intraperitoneal administration of IFN-gamma improved PF in GC-injected wild-type mice. Our results suggest that Th2 cells may play roles in the development of experimental PF and that Th1 cells may alleviate the severity of experimental PF. PMID- 26156403 TI - Oncogenic Lmo3 cooperates with Hen2 to induce hydrocephalus in mice. AB - We previously reported that LMO3 and HEN2 act as oncogenes in neuroblastoma development through up-regulating MASH1 transcription by interfering with HES1. To confirm these results in vivo, we generated transgenic mice of these genes. Lmo3 or Hen2 was expressed under the control of Wnt1 promoter, which is expressed in the central nervous system and neural crest of the sympathoadrenal lineage from which neuroblastoma develops. Heterozygous Lmo3 and Hen2 transgenic mice (Tg (Lmo3) and Tg (Hen2)) developed hydrocephalus at higher frequency than for the wild type mice, and all heterozygous double-transgenic mice (Tg (Lmo3; Hen2)) developed hydrocephalus. Therefore, Lmo3 and Hen2 may be involved in and have synergistic effects on hydrocephalus development. Although aqueduct stenosis occurred in all genotypes, it was mild in Tg (Lmo3; Hen2) mice. Furthermore, hydrocephalus was detected at E18.5 in Tg (Lmo3; Hen2). These results suggest that the causes of hydrocephalus are not only aqueduct stenosis but also disorder of neocortical development. A similar phenotype was reported in Robo1/2(-/-) mice, in which Hes1 expression level was decreased in ventricular zone progenitors. Thus, it is suggested that the expression levels of Lmo3 and/or Hen2 could determine the fate of stem cells by inhibiting Hes1 function during nervous system development and might be a trigger of aberrant neurogenesis in vivo. PMID- 26156404 TI - Protective immune-response of aluminium hydroxide gel adjuvanted phage lysate of Brucella abortus S19 in mice against direct virulent challenge with B. abortus 544. AB - The prophylactic efficacies of plain and alum adsorbed lysate were evaluated by direct virulent challenge in mice model. A recently isolated brucellaphage 'phiLd' was used for generation of lysates. Twenty four h incubated Brucella abortus S19 broth cultures standardized to contain approximately 10(8) CFU/ml were found suitable for generation of lysates. Three lysate batches produced through separate cycles did not show any significant variation with respect to protein and polysaccharide contents, endotoxin level and phage counts, indicating that compositionally stable lysate preparations can be generated through an optimized production process. Three polypeptides of ~16, 19 and 23 kDa could be identified as immuno-dominant antigens of the lysate which induced both humoral and cell-mediated immune responses in a dose dependent manner. Results of efficacy evaluation trial confirmed dose-dependent protective potencies of lysate preparation. The lysate with an antigenic dose of 0.52 MUg protein and 60 MUg CHO adsorbed on aluminium gel (0.1 percent aluminium concentration) exhibited the highest protective potency which was greater than that induced by standard S19 vaccine. Phage lysate methodology provides a very viable option through which an improved immunizing preparation with all desirable traits can be developed against brucellosis, and integrated with immunization programmes in a more efficient manner. PMID- 26156407 TI - N-Acetylcysteine Inhibits Ventilation-Induced Collagen Accumulation in the Rat Lung. AB - Mechanical ventilation is the most important life supportive therapy for patients with acute respiratory distress syndrome (ARDS). However, increasing evidence from clinical studies suggests that mechanical ventilation can cause lung fibrosis, which may significantly contribute to morbidity and mortality. Recent studies also found fibroproliferation occurred in early stage of ARDS with poor outcome. We have hypothesized that mechanical ventilation-induced lung injury may be a major contributor to lung fibrosis, and antioxidant could be a potential therapeutic agent for the treatment to mechanic ventilation induced fibroproliferation. We therefore used Sprague-Dawley rats that were ventilated with large tidal volume (20 ml/kg) or low tidal volume (7 ml/kg). We analyzed the time course of collagen level in the lung and the effect of N-acetylcysteine (NAC), a thiol antioxidant, on mechanical ventilation-induced collagen accumulation. In addition, normal human lung fibroblasts (NHLF) were exposed to mechanical stretch, which mimics ventilator-induced lung inflation, to evaluate the collagen secretion in culture medium. We found that ventilation-induced collagen accumulation occurred even after 2-hour ventilation. Pretreatment with NAC (140 mg/kg) inhibited collagen accumulation in lungs of rats ventilated with large tidal volume. Moreover, mechanical stretch caused the accumulation of collagen in the culture medium of NHLF, the magnitude of which was decreased with the pretreatment with NAC (1 mM). These results indicate that mechanical ventilation can induce collagen accumulation within 2 hours. NAC alleviated the collagen accumulation induced by mechanical ventilation with high tidal volume. Therefore, NAC can be considered as a good candidate in preventing ventilation induced lung fibrosis. PMID- 26156406 TI - Insight into the structural requirements of aminopyrimidine derivatives for good potency against both purified enzyme and whole cells of M. tuberculosis: combination of HQSAR, CoMSIA, and MD simulation studies. AB - The Mycobacterium tuberculosis protein kinase B (PknB) is critical for growth and survival of M. tuberculosis within the host. The series of aminopyrimidine derivatives show impressive activity against PknB (IC50 < .5 MUM). However, most of them show weak or no cellular activity against M. tuberculosis (MIC > 63 MUM). Consequently, the key structural features related to activity against of both PknB and M. tuberculosis need to be investigated. Here, two- and three dimensional quantitative structure-activity relationship (2D and 3D QSAR) analyses combined with molecular dynamics (MD) simulations were employed with the aim to evaluate these key structural features of aminopyrimidine derivatives. Hologram quantitative structure-activity relationship (HQSAR) and CoMSIA models constructed from IC50 and MIC values of aminopyrimidine compounds could establish the structural requirements for better activity against of both PknB and M. tuberculosis. The NH linker and the R1 substituent of the template compound are not only crucial for the biological activity against PknB but also for the biological activity against M. tuberculosis. Moreover, the results obtained from MD simulations show that these moieties are the key fragments for binding of aminopyrimidine compounds in PknB. The combination of QSAR analysis and MD simulations helps us to provide a structural concept that could guide future design of PknB inhibitors with improved potency against both the purified enzyme and whole M. tuberculosis cells. PMID- 26156405 TI - Pretreatment quality of life as a prognostic factor for early survival and functional outcomes in patients with head and neck cancer. AB - PURPOSE: Quality of life (QOL) scores in cancer patients are associated with disease course and treatment outcomes. The aim of this study was to prospectively evaluate the associations between pretreatment QOL scores and survival or functional outcomes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: This prospective study enrolled a total of 141 patients with previously untreated HNSCC who underwent curative treatments from October 2010 to March 2012. Patients completed questionnaires on QOL including the European Organization of Research and Treatment of Cancer 30-item Core QOL questionnaire (EORTC QLQ-C30) and EORTC QOL questionnaire Head and Neck Cancer module (QLQ H&N35). Univariate and multivariate analyses were used to identify QOL scores significantly associated with overall survival (OS), disease-free survival (DFS), and functional outcomes of gastrostomy or tracheostomy dependence. RESULTS: The 2 year OS and DFS rates were 82.3 and 78.0%, respectively. The rates of gastrostomy and tracheostomy dependence were 9.2 and 14.9%, respectively. After controlling for clinical factors, specific QOL indices of 'dyspnea' (hazard ratio 1.023 [95% confidence interval 1.006-1.039]) and 'appetite loss' (1.020 [1.005-1.034]) were significantly associated with OS, while 'insomnia' (1.013 [1.002-1.025]) and 'appetite loss' (1.014 [1.001-1.026]) scores were significantly predictive of DFS (P < 0.05). Global health status score (0.967 [0.935-1.000]) and fatigue (1.048 [1.010-1.086]) were significantly associated with the dependence of tracheostomy (P < 0.05). There was no relationship between gastrostomy dependence and QOL indices. CONCLUSION: This study provides evidence of significant relationships between certain pretreatment QOL measures and survival or functional outcomes in HNSCC patients. PMID- 26156408 TI - [Effects of workers' interpersonal helping behavior enhancement program]. AB - OBJECTIVES: Interpersonal helping behavior in organizational citizenship behavior can enhance social support in the workplace. The purpose of this study was to determine whether a workers' interpersonal helping behavior enhancement program increased interpersonal helping behavior, social support, and quantitative workload, and reduced psychological stress responses. METHODS: A total of 72 workers in a manufacturing company in Japan participated in this study. After excluding 24 participants due to incomplete answers to a questionnaire, retirement, or absence from training, a total of 26 participants working in branch B assigned to an intervention group (22 male and 4 female) and a total of 22 participants working in branch C assigned to a control group (19 male and 3 female) were used for per-protocol analyses. In addition, after excluding 10 participants due to incomplete answers at pre test, a total of 35 participants working in branch B assigned to an intervention group (30 male and 5 female) and a total of 27 participants working in branch C assigned to a control group (23 male and 4 female) were used for intention to treat (ITT) analyses. Interpersonal helping behavior was assessed using the Japanese version of the Organizational Citizenship Behavior Scale. The Brief Job Stress Questionnaire was used to measure quantitative workload, psychological stress responses, and social support. Only the intervention group participants attended a seminar on psychological education, performed role-playing, and did four weeks' homework (HW). Both the intervention and control group participants answered pre test (pre), post test (post), and follow-up test (follow-up) at the same times. To evaluate the effects of the workers' interpersonal helping behavior enhancement program, two-way analysis of variances were performed for per-protocol analyses. Interpersonal helping behavior, quantitative workload, psychological stress responses, and social support were used as the dependent variables, time (pre, post, follow-up) and group (intervention, control) were used as the independent variables. A linear mixed model was established for ITT analyses. RESULTS: The post and follow-up scores of interpersonal helping behavior and coworker support were significantly higher than the pre scores in per-protocol analyses. However, the follow-up scores of coworker support were not significantly higher than the pre scores in the ITT analyses. CONCLUSIONS: The workers' interpersonal helping behavior enhancement program significantly improved interpersonal helping behavior and coworker support. However, the scores of supervisor support, quantitative workload, and psychological stress responses did not change significantly. The workers' interpersonal helping behavior enhancement program may enhance interpersonal helping behavior and coworker support. PMID- 26156409 TI - [The relationship between self-awareness of fatigue symptoms and working conditions in female nurses]. AB - OBJECTIVES: The aim of this study was to clarify the relationship between self awareness of fatigue symptoms and working conditions, in female nurses. METHODS: We studied personal background, working conditions, physical symptoms, "Pittsburgh Sleep Quality Index - Japanese version (PSQI-J)", and 13 items that represented the parts related to self-awareness of the "the self-Diagnosis Checklist for Workers' Accumulated Fatigue" in 3,855 female nurses. The targets for analysis were 983 nurses ("all subjects") and among those, 765 "shift workers". The total score (fatigue symptoms self-awareness score) was calculated for 13 items that represented the parts related to self-awareness of the "the self-Diagnosis Checklist for Workers' Accumulated Fatigue". The Mann-Whitney U test and the Kruskal-Wallis test were performed, and the fatigue symptoms self awareness score was studied, based on personal background, working conditions, physical symptoms and the PSQI-J score. RESULTS: For "all subjects", there was a significant difference in the fatigue symptoms self-awareness score for department in which they work, the form the work takes, and the PSQI-J score. The fatigue symptoms self-awareness score of nurses with a PSQI-J score of 5.5 or higher was a significantly high value. For "shift workers", there was a significant difference in the fatigue symptoms self-awareness score for presence or absence of a caregiver role, department in which they work, the form the work takes, the form the nap takes during night work and PSQI-J score. There was a significantly high value in the fatigue symptoms self-awareness score of subjects with a caregiver role, subjects working in surgical wards or internal medicine wards, subjects working on a three-shift system, and subjects who were unable to take naps during night work, subjects with a PSQI-J score of 5.5 or higher. DISCUSSION: These survey results suggest that it is important to set up a system that will ensure the ability to have naps during night work. It will also be necessary to consider the caregiver role and so on as items related to the fatigue of nurses. PMID- 26156410 TI - Magnetic anisotropy, unusual hysteresis and putative "up-up-down" magnetic structure in EuTAl4Si2 (T = Rh and Ir). AB - We present detailed investigations on single crystals of quaternary EuRhAl4Si2 and EuIrAl4Si2. The two compounds order antiferromagnetically at TN1 = 11.7 and 14.7 K, respectively, each undergoing two magnetic transitions. The magnetic properties in the ordered state present a large anisotropy despite Eu(2+)being an S-state ion for which the single-ion anisotropy is expected to be weak. Two features in the magnetization measured along the c-axis are prominent. At 1.8 K, a ferromagnetic-like jump occurs at very low field to a value one third of the saturation magnetization (1/3 M0) followed by a wide plateau up to 2 T for Rh and 4 T for Ir-compound. At this field value, a sharp hysteretic spin-flop transition occurs to a fully saturated state (M0). Surprisingly, the magnetization does not return to origin when the field is reduced to zero in the return cycle, as expected in an antiferromagnet. Instead, a remnant magnetization 1/3 M0 is observed and the magnetic loop around the origin shows hysteresis. This suggests that the zero field magnetic structure has a ferromagnetic component, and we present a model with up to third neighbor exchange and dipolar interaction which reproduces the magnetization curves and hints to an "up-up-down" magnetic structure in zero field. PMID- 26156411 TI - Erratum to: bioresorbable distraction device for the treatment of airway problems for infants with Robin sequence. PMID- 26156412 TI - Functions of Coenzyme Q10 Supplementation on Liver Enzymes, Markers of Systemic Inflammation, and Adipokines in Patients Affected by Nonalcoholic Fatty Liver Disease: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder related to inflammation. Coenzyme Q10 (CoQ10) is a natural compound that has recently been considered as an anti-inflammatory factor. In the current study we aimed to evaluate the effects of CoQ10 supplementation on liver enzymes, inflammation status, and adipokines in patients with NAFLD. METHODS: Forty-one subjects with NAFLD participated in the current randomized, double-blind, placebo controlled trial. The participants were randomly divided into 2 groups: one group received CoQ10 capsules (100 mg once a day) and the other received placebo for 12 weeks. Blood samples of each patient were taken before and after the 12-week intervention period for measurement of liver aminotransferases, inflammatory biomarkers, and adipokines (adiponectin and leptin). RESULTS: Taking 100 mg CoQ10 supplement daily resulted in a significant decrease in liver aminotransferases (aspartate aminotransferase [AST] and gamma-glutamyl transpeptidase [GGT]), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha, and the grades of NAFLD in the CoQ10 group in comparison to the control group (p < 0.05). In addition, patients who received CoQ10 supplement had higher serum levels of adiponectin (p = 0.016) and considerable changes in serum leptin (p = 0.053). However, no significant changes occurred in serum levels of interleukin-6 in both groups. CONCLUSION: The present study suggested that CoQ10 supplement at a dosage of 100 mg could be effective for improving the systemic inflammation and biochemical variables in NAFLD. PMID- 26156413 TI - Lipases in Medicine: An Overview. AB - Lipases are part of the family of hydrolases that act on carboxylic ester bonds. They are involved in catalyzing the hydrolysis of triglycerides (TG) into chylomicrons and very low density lipoprotein (VLDL) particles. Uses of lipases are evolving rapidly and currently they are reported to show high potential in medicine. Intensive study and investigations have led researchers to explore lipases for their use in substitution therapy, where in enzyme deficiency during diseased conditions is compensated by their external administration. In our body, they are used to break down fats present in food so that they can be absorbed in the intestine and deficiency of lipases leads to malabsorption of fats and fat soluble vitamins. Lipases help a person who has cystic fibrosis, Alzheimer's disease, atherosclerosis and act as a candidate target for cancer prevention and therapy. They act as diagnostic tool and their presence or increasing levels can indicate certain infection or disease. Obesity causes metabolic disease and is a serious health problem around the world. Thus inhibiting digestive lipase to reduce fat absorption has become the main pharmacological approach to the treatment of obesity in recent years. PMID- 26156414 TI - Therapeutic Impact of Sphingosine 1-phosphate Receptor Signaling in Multiple Sclerosis. AB - Multiple sclerosis (MS) is a female predominant autoimmune demyelinating disease of central nervous system. The proper etiology is not clear. The existing therapies with interferon beta (Betaseron, Rebif), glatiramer acetate (copolymer 1, copaxone) are found to be promising for MS patients. The alpha-4 integrin antagonist monoclonal antibody Natalizumab has been found to decrease brain inflammation in relapsing-remitting MS via inhibition of alpha-4 beta- 1 integrinmediated mode of action of antigen -primed T cells to enter into central nervous system through blood brain barrier. The advancement of drug development introduced prospects of CD52 monoclonal antibody Alemtuzumab and CD20 monoclonal antibody Rituximab in MS therapy. The benefit versus risk ratios of these therapeutic monoclonal antibodies are currently under clinical trial. The ongoing researches demonstrated the importance of HMG-CoA reductase inhibitor statins, NF kappaBp65 inhibitor NBD peptide, and antagonist of poly-ADP-ribose polymerase (PARP) in experimental autoimmune encephalomyelitis (EAE), animal model for MS. Recently, the clinical trials indicated the therapeutic prospect of G-protein coupled sphingosine 1-phosphate receptor (S1PR) in MS patients. Recent studies showed remyelination through selective activation of oligodendrocyte progenitor cells. In the context, role of S1PR-mediated signals following interaction with natural ligand S1P and agonist Fingolimod (FTY720) gain profound therapeutic importance in prevention of demyelination in MS brain. The S1PR agonist Fingolimod (FTY 720) has recently been approved by Food and Drug Administration for MS therapy. In the review, we provided an insight on S1PR mode of action in the aspect of treatment of autoimmune disorder, re-myelination and regeneration of axons in damaged central nervous system in multiple sclerosis. PMID- 26156416 TI - A System Review of Anti-fibrogenesis Effects of Compounds Derived from Chinese Herbal Medicine. AB - Chinese herbal medicine (CHM), an alternative and complementary medicine, has been applied in various diseases. Recently, a number of anti-liver fibrogenesis compounds exhibiting antiliver fibrosis effects have been discovered in CHM. In this review, we reviewed the published data on their anti-fibrosis effects and discussed the possible underlying mechanisms. More investigations are needed to improve the insight into therapeutic effect of CHM on liver fibrosis. PMID- 26156415 TI - Synthetic Aziridines in Medicinal Chemistry: A Mini-Review. AB - Azaheterocyclic compounds are well-known to have diverse types of biological activity. Among them, azacyclopropanes, commonly referred as aziridines, occupy a prominent place in synthetic organic and medicinal chemistry due to its occurrence in natural resources, complexity involved in synthesis due to ring strain, building blocks in organic synthesis, and its biological properties. Several novel compounds containing aziridine ring have been designed and synthesized recently by medicinal chemists for evaluating their biological profile. A number of compounds are reported as cysteine protease inhibitors, antibacterial, antifungal, anticancer, antileishmanial, and antimalarial agents. This review article summarizes the biological activity of such compounds. The preparation of such compounds is also described. PMID- 26156417 TI - Nitroimidazoles, Quinolones and Oxazolidinones as Fluorine Bearing Antitubercular Clinical Candidates. AB - Tuberculosis is a leading killer of lives worldwide and the global curse of multi drug resistant tuberculosis is attaining really dangerous levels. Synergistic interaction of HIV and TB is the twin epidemics in resource-limited countries as each potentiate progression of the other. The increasing emergence of MDR-TB and XDR-TB place an immense burden for the treatment of TB with currently available drugs. The situation urgently demands for the discovery of new drugs with novel mode of action and differs in structural features in order to overcome resistance appears in conventional TB therapeutics. The present report covers the discovery of three classes of antituberculosis drugs, Nitroimidazoles, Quinolones and Oxazolidinones, undergoing clinical development with fluorine atom in their structures. Highly electronegative fluorine atom plays a signature role in advancing medicinal innovations as it existence in the drug compounds critically influences metabolic stability and lipophilicity thereby delaying its elimination by the body which results into a long term in vivo efficiency of the drug. Presence of fluorine atom(s) in the drug structures described in this report, has been associated with the several fold increase in the overall potency of the compound as demonstrated since the early discoveries. 6 Fluorinated derivatives from these three classes as pretomanid, delamanid, moxifloxacin, gatifloxacin, linezolid and sutezolid have been discussed with their antituberculosis effects, mode of action, chemical synthetic routes and results of clinical studies. PMID- 26156418 TI - Two Important Polysaccharides as Carriers for Drug Delivery. AB - Chitosan can be used to prepare the carriers, such as nanoparticles (NPs), intelligent gels, microspheres, nano/microencapsulation, and so on. Its applications in the drug delivery are more broad. Dextran can be combined with drugs by non-covalent crosslinking method or covalent modification mode in the course of delivery. The applications of chitosan and dextran as carriers for drug delivery were summed up herein. PMID- 26156419 TI - The Role of Epigenetics in the Progression of Non-Alcoholic Fatty Liver Disease. AB - Non-alcoholic fatty liver disease encompasses a spectrum of pathologies ranging from simple steatosis to non-alcoholic steatohepatitis. Patients with non alcoholic steatohepatitis have increased risk of cirrhosis, liver failure and hepatocellular carcinoma. About 25% of subjects with simple steatosis progress to steatohepatitis; nowadays, the detailed pathological factors influencing the progression of non-alcoholic fatty liver disease remains unclear. It is proposed that genetic and environmental factors interact to determine the disease phenotype. Epigenetics could explain some relationships between genes and external influences. The epigenetic changes that have been related to non alcoholic fatty liver disease are DNA methylation, onecarbon metabolism, histone modifications and the presence of micro-RNA. DNA methylation and micro-RNAs have been investigated in human samples, whereas histone modifications have only been studied until now in animal and cellular models. The aim of this study is to review the most relevant information about epigenetic changes in non-alcoholic steatohepatitis. PMID- 26156421 TI - Recent Advances in the Development of Small-Molecular Inhibitors Target HIV Integrase-LEDGF/p75 Interaction. AB - Lens epithelium-derived growth factor (LEDGF/p75) plays an essential role in the HIV-1 replication. It acts by tethering integrase (IN) into the host cellular chromatin. Due to its significance of the IN-LEDGF/p75 interaction affords a novel therapeutic approach for the design of new classes of antiretroviral agents. To date, many small molecules have been found to be the inhibitors of INLEDGF/ p75 interaction. This review summarizes recent advances in the development of potential structure-based IN-LEDGF/p75 interaction inhibitors. The work will be helpful to shed light on the antiretroviral drug development pipeline in the next future. PMID- 26156420 TI - MicroRNAs Used in Combination with Anti-Cancer Treatments Can Enhance Therapy Efficacy. AB - MicroRNAs (miRNAs), a recently discovered class of small non-coding RNAs, constitute a promising approach to anti-cancer treatments when they are used in combination with other agents. MiRNAs are evolutionarily conserved non-coding RNAs that negatively regulate gene expression by binding to the complementary sequence in the 3'-untranslated region (UTR) of target genes. MiRNAs typically suppress gene expression by direct association with target transcripts, thus decreasing the expression levels of target proteins. The delivery to cells of synthetic miRNAs that mimic endogenous miRNA targeting genes involved in the DNA Damage Response (DDR) can perturb the process, making cells more sensitive to chemotherapy or radiotherapy. This review examines how cells respond to combined therapy and it provides insights into the role of miRNAs in targeting the DDR repair pathway when they are used in combination with chemical compounds or ionizing radiation to enhance cellular sensitivity to treatments. PMID- 26156422 TI - Primordial Odontogenic Cyst with Induction Phenomenon (Zonal Fibroblastic Hypercellularity) and Dentinoid Material Versus Archegonous Cystic Odontoma: You Choose! AB - The most recent A.F.I.P. fascicle defines primordial odontogenic cyst (POC) as a distinct, nonkeratinized, odontogenic cyst of "undetermined origin" forming in the place of a developing normal or supernumerary tooth. However, the majority of examples reported in the literature under this term represent odontogenic keratocysts (keratocystic odontogenic tumors). In addition, there are rare reported cases of cystic odontomas. An 18-year-old Caucasian male presented with a unilocular mandibular radiolucent lesion in the place of a congenitally missing molar. Histologically, it featured nonkeratinizing, thin stratified squamous epithelial lining with areas of spongiosis and foci of vacuolization of individual basal cells without significant nuclear palisading. Focally, budding of the basal cell layer was identified. A zone of increased cellularity featuring induction-type fibroblasts was present subepithelially as well as dentinoid deposits with odontogenic epithelial nests. Immunohistochemically, the epithelial lining was negative for calretinin and the induction-like zone negative for S100 protein, smooth muscle actin, and CD34. The case was externally reviewed by five oral pathologists who provided various diagnostic interpretations including primordial cyst, odontogenic cyst not otherwise specified (NOS), cyst with ameloblastic changes, and unicystic ameloblastoma. At that time, a final diagnosis of odontogenic cyst NOS was rendered with a comment that it may represent a true example of POC or a cystic odontoma. The lesion has not recurred within a 13 year follow-up period after initial excision. An unusual cystic lesion is presented that may represent a true example of POC with dentinoid formation or an archegonous cystic odontoma. PMID- 26156423 TI - Diagnostic Yield of Computed Tomography in the Evaluation of Idiopathic Vocal Fold Paresis. AB - OBJECTIVE: To determine the diagnostic yield of computed tomography (CT) in establishing an etiology in patients with idiopathic unilateral vocal fold paresis (IUVFP). To determine the proportion of CT scans yielding incidental findings requiring further patient management. STUDY DESIGN: Case series with chart review. SETTING: Tertiary laryngology practice. SUBJECTS: Laryngology clinic patients under the care of the 2 senior authors. METHODS: All clinic patients were identified who had a diagnosis of IUVFP and underwent CT of the skull base to the upper mediastinum from 2004 to 2014. Demographic, historical, examination, and investigation data were extracted. CT reports and endoscopic recordings were reviewed. Patients were excluded if there were insufficient clinical findings recorded or if there was a known neurologic disorder, complete vocal fold immobility, or bilateral involvement. RESULTS: A total of 174 patients with IUVFP who had also undergone contrast-enhanced CT were identified. Of the 174 patients, 5 had a cause for their paresis identified on CT. This equated to a diagnostic yield of 2.9% (95% confidence interval, 0.94% to 6.6%). Of the 174 patients, 48 had other incidental lesions identified that required further follow up, investigation, or treatment. This equated to an incidental yield of 27.6% (95% confidence interval, 21.1% to 34.9%). CONCLUSION: This is the second and largest study to evaluate the diagnostic yield of CT in the evaluation of IUVFP. It demonstrates a low diagnostic yield and a high incidental yield. These findings suggest that the routine use of CT in the evaluation of idiopathic vocal fold paresis should be given careful consideration and that a tailored approach to investigation with good otolaryngologic follow-up is warranted. PMID- 26156424 TI - The Aging Voice: Influence of Respiratory and Laryngeal Changes. AB - OBJECTIVES: To evaluate the impact on voice quality of 2 pathogenic factors involved in age-related dysphonia: glottal gap and decline in respiratory function. STUDY DESIGN: Cross-sectional prospective. SETTINGS: Tertiary referral center. SUBJECTS AND METHODS: A total of 105 healthy patients >=65 years old were included, with a maximum phonation time <=15 seconds for men and <=12 seconds for women. Laryngostroboscopy and spirometry were conducted to assess the glottal gap and respiratory function, and 4 profiles were defined according to their combination: glottal deficit, respiratory deficit, combined deficit, and no deficit. Differences across profiles in phonation times, acoustic parameters, and GRBAS scale and Voice Handicap Index-10 scores were analyzed according to Kruskal Wallis and Mann-Whitney nonparametric tests. Multiple regression was performed to estimate the influence of each pathogenic factor. RESULTS: Respiratory deficit was the most frequent profile (37%). When compared to the other groups, patients with combined deficit had shorter phonation times for men (8.5 seconds; Kruskal Wallis, P = .009) and women (7.8 seconds; P = .003), worse jitter (8.3%; P = .001), GRBAS scale (5.8; P < .001), and Voice Handicap Index-10 (7.7; P = .002). CONCLUSION: Age-related respiratory and laryngeal changes have a negative impact on vocal quality, especially when both deficits are present. PMID- 26156425 TI - Using stem cells to produce insulin. AB - INTRODUCTION: Tremendous progress has been made in generating insulin-producing cells from pluripotent stem cells. The best outcome of the refined protocols became apparent in the first clinical trial announced by ViaCyte, based on the implantation of pancreatic progenitors that would further mature into functional insulin-producing cells inside the patient's body. AREAS COVERED: Several groups, including ours, have contributed to improve strategies to generate insulin producing cells. Of note, the latest results have gained a substantial amount of interest as a method to create a potentially functional and limitless supply of beta-cell to revert diabetes mellitus. This review analyzes the accomplishments that have taken place over the last few decades, summarizes the state-of-art methods for beta-cell replacement therapies based on the differentiation of embryonic stem cells into glucose-responsive and insulin-producing cells in a dish and discusses alternative approaches to obtain new sources of insulin producing cells. EXPERT OPINION: Undoubtedly, recent events preface the beginning of a new era in diabetes therapy. However, in our opinion, a number of significant hurdles still stand in the way of clinical application. We believe that the combination of the private and public sectors will accelerate the process of obtaining the desired safe and functional beta-cell surrogates. PMID- 26156426 TI - Efficient Red-Emitting Platinum Complex with Long Operational Stability. AB - A tetradentate cyclometalated Pt(II) complex, PtN3N-ptb, was developed as an emissive dopant for stable and efficient red phosphorescent OLEDs. Devices employing PtN3N-ptb in electrochemically stable device architectures achieved long operational lifetimes with estimated LT97, of over 600 h at luminances of 1000 cd/m(2). Such long operational lifetimes were achieved utilizing only literature reported host, transporting and blocking materials with known molecular structures. Additionally, a thorough study of the effects of various host and transport materials on the efficiency, turn on voltage, and stability of the devices was carried out. Ultimately, maximum forward viewing EQEs as high as 21.5% were achieved, demonstrating that Pt(II) complexes can act as stable and efficient dopants with operational lifetimes comparable or superior to those of the best literature-reported Ir(III) complexes. PMID- 26156427 TI - Effects of dexamethasone, a synthetic glucocorticoid, on human periodontal ligament stem cells. AB - Recent studies have showed that psychosocial stress causes elevated secretion of cortisol, the principal glucocorticoid (GC), and thus increases the extent of periodontal breakdown. In this study, we investigated whether stress-associated periodontal disturbance may be due to GC-induced changes in the periodontal ligament stem cells (PDLSCs), one of the most promising candidates for periodontal tissue regeneration. Our results in this study showed that dexamethasone (Dex) treatment causes the translocation of the glucocorticoid receptor (GR) into the nucleus and increases the expression of many genes, including dickkopf-1 (DKK-1) in PDLSCs. ELISA showed that DKK-1 is secreted from PDLSCs in response to Dex treatment. The GR antagonist RU486 attenuated the Dex inducible DKK-1 messenger RNA (mRNA) expression. DKK-1 inhibited the growth of PDLSCs and suppressed Wnt-mediated activation of beta-catenin signaling in PDLSCs. Our results strongly suggest that stress-associated periodontal disturbance may be due to GC-induced changes in the activity of PDLSCs via DKK-1 expression and might provide a possible explanation for the deteriorating effect of stress on periodontal breakdown. PMID- 26156428 TI - Concise diastereoselective synthesis of calcaripeptide C via asymmetric transfer hydrogenation/Pd-induced chiral allenylzinc as a key reaction. AB - Synthesis of the natural product calcaripeptide C derived from the fungal metabolite mycelium KF525 of Calcarisporium sp. has been achieved. This complementary approach avoids the use of a stoichiometric amount of chiral auxiliary reagents as commonly used to generate enantioenriched advanced precursors. The enantioselective synthesis of calcaripeptide C is remarkable in that using catalytic reactions sets the two stereogenic centers efficiently with good levels of enantioselectivity. Further diversification of the calcaripeptide C structures is possible by employing a complementary catalytic enantioenriched Ru-catalyst. PMID- 26156429 TI - Effects of Agmatine on Depressive-Like Behavior Induced by Intracerebroventricular Administration of 1-Methyl-4-phenylpyridinium (MPP(+)). AB - Considering that depression is a common non-motor comorbidity of Parkinson's disease and that agmatine is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system disorders, this study investigated the antidepressant-like effect of agmatine in mice intracerebroventricularly (i.c.v.) injected with the dopaminergic neurotoxin 1 methyl-4-phenylpyridinium (MPP(+)). Male C57BL6 mice were treated with agmatine (0.0001, 0.1 or 1 mg/kg) and 60 min later the animals received an i.c.v. injection of MPP(+) (1.8 ug/site). Twenty-four hours after MPP(+) administration, immobility time, anhedonic behavior, and locomotor activity were evaluated in the tail suspension test (TST), splash test, and open field test, respectively. Using Western blot analysis, we investigated the putative modulation of MPP(+) and agmatine on striatal and frontal cortex levels of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF). MPP(+) increased the immobility time of mice in the TST, as well as induced an anhedonic-like behavior in the splash test, effects which were prevented by pre-treatment with agmatine at the three tested doses. Neither drug, alone or in combination, altered the locomotor activity of mice. I.c.v. administration of MPP(+) increased the striatal immunocontent of TH, an effect prevented by the three tested doses of agmatine. MPP(+) and agmatine did not alter the immunocontent of BDNF in striatum and frontal cortex. These results demonstrate for the first time the antidepressant like effects of agmatine in an animal model of depressive-like behavior induced by the dopaminergic neurotoxin MPP(+). PMID- 26156430 TI - MYCNOS functions as an antisense RNA regulating MYCN. AB - Amplification or overexpression of neuronal MYC (MYCN) is associated with poor prognosis of human neuroblastoma. Three isoforms of the MYCN protein have been described as well as a protein encoded by an antisense transcript (MYCNOS) that originates from the opposite strand at the MYCN locus. Recent findings suggest that some antisense long non-coding RNAs (lncRNAs) can play a role in epigenetically regulating gene expression. Here we report that MYCNOS transcripts function as a modulator of the MYCN locus, affecting MYCN promoter usage and recruiting various proteins, including the Ras GTPase-activating protein-binding protein G3BP1, to the upstream MYCN promoter. Overexpression of MYCNOS results in a reduction of upstream MYCN promoter usage and increased MYCN expression, suggesting that the protein-coding MYCNOS also functions as a regulator of MYCN ultimately controlling MYCN transcriptional variants. The observations presented here demonstrate that protein-coding transcripts can regulate gene transcription and can tether regulatory proteins to target loci. PMID- 26156431 TI - Does electronic medication reconciliation at hospital discharge decrease prescription medication errors? AB - PURPOSE: Medication errors are an important patient safety issue. Electronic medication reconciliation is a system designed to correct medication discrepancies at transitions in healthcare. The purpose of this paper is to measure types and prevalence of intravenous antibiotic errors at hospital discharge before and after the addition of an electronic discharge medication reconciliation tool (EDMRT). DESIGN/METHODOLOGY/APPROACH: A retrospective study was conducted at a tertiary hospital where house officers order discharge medications. In total, 100 pre-EDMRT and 100 post-EDMRT subjects were randomly recruited from the study center's clinical Outpatient Parenteral Antimicrobial Therapy (OPAT) program. Using infectious disease consultant recommendations as gold standard, each antibiotic listed in these consultant notes was compared to the hospital discharge orders to ascertain the primary outcome: presence of an intravenous antibiotic error in the discharge orders. The primary covariate of interest was pre- vs post-EDMRT group. After generating the crude prevalence of antibiotic errors, logistic regression accounted for potential confounding: discharge day (weekend vs weekday), average years of practice by prescribing physician, inpatient service (medicine vs surgery) and number of discharge mediations per patient. FINDINGS: Prevalence of medication errors decreased from 30 percent (30/100) among pre-EDMRT subjects to 15 percent (15/100) errors among post-EDMRT subjects. Dosage errors were the most common type of medication error. The adjusted odds ratio of discharge with intravenous antibiotic error in the post-EDMRT era was 0.39 (0.18, 0.87) compared to the pre-EDMRT era. In the adjusted model, the total number of discharge medications was associated with increased OR of discharge error. ORIGINALITY/VALUE: To the authors' knowledge, no other study has examined the impact of reconciliation on types and prevalence of medication errors at hospital discharge. The focus on intravenous antibiotics as a class of high-stakes medications with serious risks to patient safety during error events highlights the clinical importance of the findings. Electronic medication reconciliation may be an important tool in efforts to improve patient safety. PMID- 26156432 TI - Quantitative comparisons of urgent care service providers. AB - PURPOSE: The purpose of this paper is to develop, validate, and use a survey instrument to measure and compare the perceived quality of three types of US urgent care (UC) service providers: hospital emergency rooms, urgent care centres (UCC), and primary care physician offices. DESIGN/METHODOLOGY/APPROACH: This study develops, validates, and uses a survey instrument to measure/compare differences in perceived service quality among three types of UC service providers. Six dimensions measured the components of service quality: tangibles, professionalism, interaction, accessibility, efficiency, and technical quality. FINDINGS: Primary care physicians' offices scored higher for service quality and perceived value, followed by UCC. Hospital emergency rooms scored lower in both quality and perceived value. No significant difference was identified between UCC and primary care physicians across all the perspectives, except for interactions. RESEARCH LIMITATIONS/IMPLICATIONS: The homogenous nature of the sample population (college students), and the fact that the respondents were recruited from a single university limits the generalizability of the findings. PRACTICAL IMPLICATIONS: The patient's choice of a health care provider influences not only the continuity of the care that he or she receives, but compliance with a medical regime, and the evolution of the health care landscape. SOCIAL IMPLICATIONS: This work contributes to the understanding of how to provide cost effective and efficient UC services. ORIGINALITY/VALUE: This study developed and validated a survey instrument to measure/compare six dimensions of service quality for three types of UC service providers. The authors provide valuable data for UC service providers seeking to improve patient perceptions of service quality. PMID- 26156433 TI - Patient safety culture: finding meaning in patient experiences. AB - PURPOSE: The purpose of this paper is to determine what patient and family stories can tell us about patient safety culture within health care organizations and how patients experience patient safety culture. DESIGN/METHODOLOGY/APPROACH: A total of 11 patient and family stories of adverse event experiences were examined in September 2013 using publicly available videos on the Canadian Patient Safety Insitute web site. Videos were transcribed verbatim and collated as one complete data set. Thematic analysis was used to perform qualitative inquiry. All qualitative analysis was done using NVivo 10 software. FINDINGS: A total of three themes were identified: first, Being Passed Around; second, Not Having the Conversation; and third, the Person Behind the Patient. Results from this research also suggest that while health care organizations and providers might expect patients to play a larger role in managing their health, there may be underlying reasons as to why patients are not doing so. PRACTICAL IMPLICATIONS: The findings indicate that patient experiences and narratives are useful sources of information to better understand organizational safety culture and patient experiences of safety while hospitalized. Greater inclusion and analysis of patient safety narratives is important in understanding the needs of patients and how patient safety culture interventions can be improved to ensure translation of patient safety strategies at the frontlines of care. ORIGINALITY/VALUE: Greater acknowledgement of the patient and family experience provides organizations with an integral perspective to assist in defining and addressing deficiencies within their patient safety culture and to identify opportunities for improvement. PMID- 26156434 TI - Introducing modern technology to promote transparency in health services. AB - PURPOSE: Quantitative indicators show that Bangladeshi maternal and child healthcare is progressing satisfactorily. However, healthcare quality is still inadequate. It is hypothesised that modern technology enhances healthcare quality. Therefore, the purpose of this paper is to investigate how modern technology such as electronic record keeping and the internet can contribute to enhancing Bangladeshi healthcare quality. This study also explores how socio economic and political factors affect the healthcare quality. DESIGN/METHODOLOGY/APPROACH: This paper is based on a qualitative case study involving 68 in-depth interviews with healthcare professionals, elected representatives, local informants and five focus group discussions with healthcare service users to understand technology's effect on health service quality. The study has been conducted in one rural and one urban service organisations to understand how various factors contribute differently to healthcare quality. FINDINGS: The findings show that modern technology, such as the internet and electronic devices for record keeping, contribute significantly to enhancing health service transparency, which in turn leads to quality health and family planning services. The findings also show that information and communication technology (ICT) is an effective mechanism for reducing corruption and promoting transparency. However, resource constraints impact adversely on the introduction of technology, which leads to less transparent healthcare. Progress in education and general socio-economic conditions makes it suitable to enhance ICT usage, which could lead to healthcare transparency, but political and bureaucratic factors pose a major challenge to ensure transparency. PRACTICAL IMPLICATIONS: This paper can be a useful guide for promoting governance and healthcare quality in developing countries including Bangladesh. It analyses the ICT challenges that healthcare staff face when promoting transparent healthcare. ORIGINALITY/VALUE: This paper provides a deeper understanding of transparency and healthcare quality in an ICT context using empirical data, which has not been explored in Bangladesh. This critical thinking is useful for policy makers and healthcare practitioners for promoting health service quality. PMID- 26156435 TI - Quality of Big Data in health care. AB - PURPOSE: The current trend in Big Data analytics and in particular health information technology is toward building sophisticated models, methods and tools for business, operational and clinical intelligence. However, the critical issue of data quality required for these models is not getting the attention it deserves. The purpose of this paper is to highlight the issues of data quality in the context of Big Data health care analytics. DESIGN/METHODOLOGY/APPROACH: The insights presented in this paper are the results of analytics work that was done in different organizations on a variety of health data sets. The data sets include Medicare and Medicaid claims, provider enrollment data sets from both public and private sources, electronic health records from regional health centers accessed through partnerships with health care claims processing entities under health privacy protected guidelines. FINDINGS: Assessment of data quality in health care has to consider: first, the entire lifecycle of health data; second, problems arising from errors and inaccuracies in the data itself; third, the source(s) and the pedigree of the data; and fourth, how the underlying purpose of data collection impact the analytic processing and knowledge expected to be derived. Automation in the form of data handling, storage, entry and processing technologies is to be viewed as a double-edged sword. At one level, automation can be a good solution, while at another level it can create a different set of data quality issues. Implementation of health care analytics with Big Data is enabled by a road map that addresses the organizational and technological aspects of data quality assurance. PRACTICAL IMPLICATIONS: The value derived from the use of analytics should be the primary determinant of data quality. Based on this premise, health care enterprises embracing Big Data should have a road map for a systematic approach to data quality. Health care data quality problems can be so very specific that organizations might have to build their own custom software or data quality rule engines. ORIGINALITY/VALUE: Today, data quality issues are diagnosed and addressed in a piece-meal fashion. The authors recommend a data lifecycle approach and provide a road map, that is more appropriate with the dimensions of Big Data and fits different stages in the analytical workflow. PMID- 26156436 TI - Resource utilization in surgery after the revision of surgical fee schedule in Japan. AB - PURPOSE: The purpose of this paper is to examine whether the current surgical reimbursement system in Japan reflects resource utilization after the revision of fee schedule in 2014. DESIGN/METHODOLOGY/APPROACH: The authors collected data from all the surgical procedures performed at Teikyo University Hospital from April 1 through September 30, 2014. The authors defined the decision-making unit as a surgeon with the highest academic rank in the surgery. Inputs were defined as the number of medical doctors who assisted surgery, and the time of operation from skin incision to closure. An output was defined as the surgical fee. The authors calculated surgeons' efficiency scores using data envelopment analysis. FINDINGS: The efficiency scores of each surgical specialty were significantly different (p=0.000). ORIGINALITY/VALUE: This result demonstrates that the Japanese surgical reimbursement scales still fail to reflect resource utilization despite the revision of surgical fee schedule. PMID- 26156437 TI - Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions In Vitro and In Vivo. AB - Semaphorin 3F (SEMA3F) provides neuronal guidance cues via its ability to bind neuropilin 2 (NRP2) and Plexin A family molecules. Recent studies indicate that SEMA3F has biological effects in other cell types, however its mechanism(s) of function is poorly understood. Here, we analyze SEMA3F-NRP2 signaling responses in human endothelial, T cell and tumor cells using phosphokinase arrays, immunoprecipitation and Western blot analyses. Consistently, SEMA3F inhibits PI 3K and Akt activity, and responses are associated with the disruption of mTOR/rictor assembly and mTOR-dependent activation of the RhoA GTPase. We also find that the expression of vascular endothelial growth factor, as well as mTOR inducible cellular activation responses and cytoskeleton stability are inhibited by SEMA3F-NRP2 interactions in vitro. In vivo, local and systemic overproduction of SEMA3F reduces tumor growth in NRP2-expressing xenografts. Taken together, SEMA3F regulates mTOR signaling in diverse human cell types, suggesting that it has broad therapeutic implications. PMID- 26156438 TI - Protective effect of sesamol against 60Co gamma-ray-induced hematopoietic and gastrointestinal injury in C57BL/6 male mice. AB - Protection of gamma-ray-induced injury in hematopoietic and gastrointestinal (GI) systems is the rationale behind developing radioprotectors. The objective of this study, therefore, was to investigate the radioprotective efficacy and mechanisms underlying sesamol in amelioration of gamma-ray-induced hematopoietic and GI injury in mice. C57BL/6 male mice were pre-treated with a single dose (100 or 50 mg/kg, 30 min prior) of sesamol through the intraperitoneal route and exposed to LD50/30 (7.5 Gy) and sublethal (5 Gy) dose of gamma-radiation. Thirty-day survival against 7.5 Gy was monitored. Sesamol (100 mg/kg) pre-treatment reduced radiation-induced mortality and resulted survival of about 100% against 7.5 Gy of gamma-irradiation. Whole-body irradiation drastically depleted hematopoietic progenitor stem cells in bone marrow, B cells, T cell subpopulations, and splenocyte proliferation in the spleen on day 4, which were significantly protected in sesamol pre-treated mice. This was associated with a decrease of radiation-induced micronuclei (MN) and apoptosis in bone marrow and spleen, respectively. Sesamol pre-treatment inhibited lipid peroxidation, translocation of gut bacteria to spleen, liver, and kidney, and enhanced regeneration of crypt cells in the GI system. In addition, sesamol pre-treatment reduced the radiation induced pattern of expression of p53 and Bax apoptotic proteins in the bone marrow, spleen, and GI. This reduction in apoptotic proteins was associated with the increased anti-apoptotic-Bcl-x and PCNA proteins. Further, assessment of antioxidant capacity using ABTS and DPPH assays revealed that sesamol treatment alleviated total antioxidant capacity in spleen and GI tissue. In conclusion, the results of the present study suggested that sesamol as a single prophylactic dose protects hematopoietic and GI systems against gamma-radiation-induced injury in mice. PMID- 26156439 TI - [Personality traits in patients with chronic migraine: a categorial and dimensional study in a series of 30 patients]. AB - INTRODUCTION: The pathogenic role of personality in migraine has not yet been defined. It can be studied by means of dimensional or categorial measurement instruments, although there is no agreement as to the most suitable approach in this respect either. AIM: To analyse the personality of patients with chronic migraine from the dimensional and categorial point of view. PATIENTS AND METHODS: We used the Salamanca questionnaire as our categorial test and, as the dimensional test, we employed the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Mood disorders were evaluated with the hospital anxiety and depression scale and the impact of migraine was determined by means of the Headache Impact Test-6 (HIT-6). RESULTS: We included 30 patients (26 females), with a mean age of 40.7 +/- 9.6 years. One case (3.3%) presented criteria for depression and four (13.3%) for anxiety. In the Salamanca test, the most common personality traits were those included within cluster C: anankastic (n = 28; 93.3%), anxious (n = 18; 60%) and dependent (n = 7; 23.3%). On the MMPI-2, 16 patients (53.3%) fulfilled criteria for hypochondria; 7 (23.3%) for depression; and 10 (33.3%) for hysteria, which are traits included within the neurotic triad. A pattern called 'conversion V' was observed. No correlation was found between the personality traits and the length of time with chronic migraine, the intensity measured by HIT-6 or the excessive use of symptomatic medication. CONCLUSIONS: In the analysis of the personality in chronic migraine, what stood out from the dimensional point of view was neuroticism and as regards the categorial perspective, the obsessive-compulsive or anankastic trait was the most salient. More extensive series need to be conducted, together with comparisons with episodic migraine and population control. PMID- 26156440 TI - [Multisite study for norming and standardizing neuropsychological instruments in healthy people for Spanish population: methods and characteristics of Normacog project]. AB - INTRODUCTION: Many neuropsychological tests used in Spain have been normed on Spanish-speaking persons in the USA and South America. In addition, the normative samples often span limited age or educational ranges, potentially decreasing their representativeness of the population, the interpretation of test results, and clinical decisions based on them. This study is part of the Normacog project which seeks to standardize neuropsychological instruments in a representative sample of Spanish society. AIM: To present the normalization methodology undertaken in the Normacog project and the sociodemographic characteristics of participants and Spanish population. SUBJECTS AND METHODS: Seven hundred and eleven participants aged 18-90 years were recruited from different geographical regions in Spain. Their sociodemographic characteristics, medical history, habits, native language, bilingualism and handedness were taken into account. Each participant completed 19 tests that assess a wide variety of cognitive domains such as verbal and visual memory, executive functions, processing speed or naming and verbal fluency. RESULTS: The final normative sample mirrors the population of Spain in age, education, and sex distributions. CONCLUSIONS: This article describes the normalization methodology and the characteristics of participants included in the multicenter Normacog study. This study seeks to standardize and normalize neuropsychological instruments, taking into account the sociodemographic characteristics of Spanish population. The Normacog project will provide normative data that are appropriate to our cultural environment, and essential for using these measures to form reliable clinical and diagnostic inferences. PMID- 26156441 TI - [Drooling therapy in children with neurological disorders]. AB - INTRODUCTION: Drooling is the inability to retain saliva in the mouth and its progression to the digestive tract, being a common problem in pediatric patients with neurological disorders. Three different treatment options are available. AIM: To assess the effectiveness and safety of trihexyphenidyl, scopolamine and botulinum toxin infiltration in the treatment of drooling in children with neurological disorders. PATIENTS AND METHODS: This is an open and prospective type study. We include patients treated in the Neurology Service that present excessive drooling, affecting their quality of life, between 2009 and 2013. RESULTS: We enrolled 46 patients in the study. The treatment with oral trihexyphenidyl was indicated in 46, obtaining good result in 15 (32.6%), three with temporary effect and the rest with lasting effect. Three patients presented side effects (6.5%). Four out of 11 (36.36%) patients treated with scopolamine patch had beneficial effects. One was withdrawn due to lack of efficacy and six due to side effects. Twenty-five patients were infiltrated with botulinum toxin, with a significant decrease of drooling in 16 patients (64%) after the first injection. We observed no significant changes in nine patients. Only one out of 25 showed side effects (mild dysphagia). CONCLUSIONS: Currently there is not a fully effective therapeutic option for drooling. We recommend starting treatment with trihexyphenidyl. A second option could be the scopolamine patch and botulinum toxin as a third option. Botulinum toxin infiltration in salivary glands is shown as an effective and safe alternative in our study. PMID- 26156442 TI - [Aicardi syndrome with Dandy-Walker type malformation]. AB - INTRODUCTION: Aicardi syndrome (OMIM 304050) was first described in 1965. Its classic triad consists of infantile spasms, partial or total agenesis of the corpus callosum and ocular disorders, such as chorioretinal lacunae. It has been posited that it is due to a mechanism involving X-linked dominant inheritance. CASE REPORT: We report the case of a full-term female, with no pathological familial history or parental consanguinity, with a prenatal diagnosis of Dandy Walker type malformation, who presented convulsions, coloboma of the optic nerve, thoracic vertebral block with presence of scoliosis, transfontanellar ultrasound imaging showing agenesis of the corpus callosum and karyotype 46,XX. She was diagnosed with Aicardi syndrome and died at the age of one and a half months. The autopsy revealed supratentorial hydrocephalus with the presence of choroid plexus papilloma, a cyst in the posterior fossa (fourth ventricle), hypoplasia of the cerebellar vermis, agenesis of the left hemisphere of the corpus callosum and cerebellum, characteristic facial features of the syndrome, ogival palate, pectus excavatum, scoliosis, paraovarian cyst and hepatomegaly. CONCLUSIONS: Few cases of an association between the pathology and the presence of Dandy-Walker malformation have been described. We report a new case of the association, bearing in mind that the related disorders, mainly agenesis or hypoplasia of the corpus callosum, suggest the existence of an underlying genetic component. A study of the search for the aetiology must be focused on evaluating those genes that are related with neurodevelopment and its activation in the organogenesis stage. The definitive diagnosis establishes the prognosis, management and genetic counselling of the family. PMID- 26156443 TI - [Posterior reversible encephalopathy: beyond the original description]. AB - INTRODUCTION: Posterior reversible encephalopathy (PRE) is a clinical and radiological entity that is typically characterized by headache, visual disturbances and seizures associated with cortical and subcortical reversible vasogenic edema in neuroimaging. AIM: To present a review of the pathophysiology of this entity, and also the associations of the PRE described in the literature. DEVELOPMENT: Given its clinical presentation, often nonspecific and variable, magnetic resonance imaging is essential for diagnosis. There are a number of well known triggers, such as hypertensive crisis, eclampsia or certain drugs. The description of increasingly atypical cases from clinical and radiological point of view, and possible new triggers, requires a redefinition of this entity. CONCLUSIONS: The PRE is a set of clinical and radiological manifestations that may not be framed within the word 'syndrome'. Although, the PRE has been reported in some cases irreversible, reversibility concept should be maintained in the definition of this entity, since in most cases the rapid control of the triggering condition allows reversibility of the lesions. PMID- 26156444 TI - [Epidermic growth factor receptor (EGFR) in glioblastomas: the mechanism of tumorigenesis and its role as a therapeutic target]. AB - A glioblastoma is a primary brain tumour that is very aggressive and resistant to conventional treatment with chemo- or radiotherapy. Given that epidermic growth factor receptor (EGFR) is altered in 50% of glioblastomas, it is currently one of the most promising therapeutic targets in this kind of tumour. Yet, inhibitors of the kinase activity of EGFR have yielded poor results in clinical trials with patients with glioblastomas. In this review we analyse the function of EGFR in glioblastomas and outline the therapeutic approaches aimed against this receptor in this kind of tumour. This sort of analysis could be a starting point for improving the design of future therapies for glioblastomas, based on inhibiting the EGFR function. PMID- 26156445 TI - [Deletion of the RPS6KA3 gene in a female with a classical phenotype of Coffin Lowry syndrome including stimulus-induced drop attacks]. PMID- 26156447 TI - Evidence-based medicine remains one's best defense against quackery. PMID- 26156446 TI - Usefulness of suPAR in the risk stratification of patients with sepsis admitted to the emergency department. AB - To investigate the role of suPAR in patients with sepsis admitted to the Emergency Department (ED). We performed multicentre prospective trial including patients admitted to the ED of three different Italian hospitals. Patients were studied upon admission on day 1, 2, 4 and 7. They were subdivided into two groups: sepsis (group 1) and severe sepsis or septic shock (group 2). The two groups were comparable for age, gender and CRP level on day 1. Patients with severe sepsis or septic shock displayed significantly higher baseline levels of suPAR, PCT and lactate. In both groups, suPAR decreased across the time (p < 0.0005). Group 1 was not different from group 2 (p = 0.545) in mortality at 7 days, while group 2 had higher mortality at 30 days than group 1 (p = 0.022). At the multivariate analysis, lactate1 (p = 0.012) and age (p = 0.019) were independent predictors of mortality at 7 days, whereas suPAR1 (p = 0.023) and age (p = 0.032) were independent predictors of mortality at 30 days. Lactate and suPAR resulted the most predictive biomarkers in the risk stratification of patients with suspected infection initially admitted to the ED, according to their role in predicting 7- and 30-day mortality, respectively. PMID- 26156448 TI - Acute deep vein thrombosis (DVT) of the lower limbs in a 32-year-old man with chronic hypoplasia of the inferior vena cava (HIVC) without risk factors. PMID- 26156449 TI - Guided bone regeneration in standardized calvarial defects using beta-tricalcium phosphate and collagen membrane: a real-time in vivo micro-computed tomographic experiment in rats. AB - Guided bone regeneration (GBR) procedures using graft materials have been used for reconstruction of osseous defects. The aim of the present in vivo micro computed tomographic (uCT) and histologic study was to assess in real time the bone regeneration at GBR sites in standardized experimental calvarial defects (diameter 3.3 mm) using beta-tricalcium phosphate (beta-TCP) with and without collagen membrane (CM). A single full-thickness calvarial defect was created on the left parietal bone in young female Wistar albino rats (n = 30) weighing approximately 300 g and aged about 6 weeks. The animals were randomly divided into three groups for treatment, based on calvarial defect filling material: (1) control group (n = 10); (2) beta-TCP + CM group (n = 10); (3) beta-TCP group (n = 10). Real-time in vivo uCT analyses were performed immediately after surgery and at 2, 4, 6 and 10 weeks to determine the volume and mineral density of the newly formed bone (BVNFB, MDNFB) and remaining beta-TCP particles (VRBP, MDRBP). The animals were killed at 10 weeks and calvarial specimens were evaluated histologically. In the control group, MDNFB increased significantly at 6 weeks (0.32 +/- 0.002 g/mm(3), P < 0.01) compared to that at baseline. In beta-TCP + CM group, BVNFB (1.10 +/- 0.12 mm(3), P < 0.01) and MDNFB (0.13 +/- 0.02 g/mm(3), P < 0.01) significantly increased at the 4th week than baseline. In the beta-TCP group, BVNFB (1.13 +/- 0.12 mm(3), P < 0.01) and MDNFB (0.14 +/- 0.01 g/mm(3), P < 0.01) significantly increased at 6 weeks compared to that at baseline. Significant reduction in VRBP was neither seen in the beta-TCP + CM group nor in the beta-TCP group. While in the beta-TCP + CM group MDRBP was reduced significantly at 6 weeks (0.44 +/- 0.9 g/mm(3), P < 0.01) from baseline (0.98 +/- 0.03 g/mm(3)), similar significant reduction in MDRBP from baseline (0.92 +/- 0.07 g/mm(3)) was seen only at 10 weeks (0.45 +/- 0.06 g/mm(3), P < 0.05) in the beta-TCP group. Histologic findings at 10 weeks revealed greater amount of NFB with osteocytes in the matrix, in the beta-TCP + CM group than in the beta-TCP group. Biomechanical assessment of NFB for hardness (H) and elastic modulus (E) revealed significantly higher values for the beta-TCP + CM group (H = 612.6 +/- 4.28 Mpa; E = 13.57 +/- 0.07 Gpa) when compared to those of the control (H = 192.1 +/- 4.93 Mpa; E = 6.76 +/- 0.04 Gpa) and the beta-TCP groups (H = 241.9 +/- 6.29 Mpa; E = 4.34 +/- 0.06 Gpa). In conclusion, based on real-time assessment, NFB is formed in calvarial defects as early as 4 weeks following GBR with beta TCP + CM as compared to 6 weeks when beta-TCP alone was used. PMID- 26156450 TI - Simulating backspatter of blood from cranial gunshot wounds using pig models. AB - Few studies have examined the biomechanical basis for backspatter from cranial gunshot wounds. Backspatter is material which travels against the direction of fire following ejection from a gunshot entrance wound. Our paper focuses on the use of animals for reconstructing this phenomenon. Five live pigs and several slaughtered pigs were shot using either 9 * 19 mm, 115 grain, full metal jacketed ammunition or .22 long rifle, 40 grain, lead, round-nose ammunition. A high-speed camera was used to record the entrance wound formation and backspatter. A small amount of backspattered material was produced with all targets, and blood backspatter was seen in a few cases. However, we conclude that our model provides an understanding of the phenomenon of backspatter and the physical mechanisms associated with it. The various components of the mechanism of backspatter formation are complex and overlap. The principle mechanism observed in pig cranial gunshots was the high-speed impact response of the skin overlying the skull bone. This study has also produced evidence supporting the view that backspatter can result from the splashing of superficial blood if it is already present on the skin. Subcutaneous gas effects have been demonstrated for backspatter from contact shots. There has been no clear evidence of the role of the collapse of a temporary cavity within the brain. PMID- 26156451 TI - Postmortem computed tomography (PMCT) and autopsy in deadly gunshot wounds--a comparative study. AB - INTRODUCTION: Postmortem computed tomography (PMCT) data in gunshot-related death were evaluated by two reader groups and compared to the gold standard autopsy for the determination of forensic pathology criteria. MATERIALS AND METHODS: Reader group I consisted of two board-certified radiologists whereas one board-certified radiologist and one board-certified forensic pathologist formed group II. PMCT data of 51 gunshot-related deaths were evaluated for the forensic pathology criteria number of gun shots, localization of gunshot injury, caliber, and direction of the gunshot differentiating between entry and exit wound as well as associated injury to surrounding tissue. The results of both reader groups were compared to the each other and to autopsy findings considered as gold standard. RESULTS: Reader groups I and II and as gold standard the autopsy evaluation showed in general a good correlation between all results. The overall discrepancy rate was 12/51 (23.4%) cases for group I and 8/51 (15.6%) for group II. DISCUSSION: Ultimately, the designated reader is able to draw the following conclusion from the presented data. At first, physical autopsy is better than PMCT regarding the localization of most gunshot injuries. Second, PMCT presents with better results than physical autopsy in locating fragmented bullets/fragment clouds, and finally, PMCT results of two radiologists were equivalent to the results of one evaluating radiologist and one pathologist with the exception of caliber assessment. However, referring to the pure numbers, the slight but not significant difference in the overall discrepancy rate of both reader groups might indicate the advantage of combining expertise in evaluating imaging in cases of gunshot-related death. PMID- 26156455 TI - Perspective: Sloppiness and emergent theories in physics, biology, and beyond. AB - Large scale models of physical phenomena demand the development of new statistical and computational tools in order to be effective. Many such models are "sloppy," i.e., exhibit behavior controlled by a relatively small number of parameter combinations. We review an information theoretic framework for analyzing sloppy models. This formalism is based on the Fisher information matrix, which is interpreted as a Riemannian metric on a parameterized space of models. Distance in this space is a measure of how distinguishable two models are based on their predictions. Sloppy model manifolds are bounded with a hierarchy of widths and extrinsic curvatures. The manifold boundary approximation can extract the simple, hidden theory from complicated sloppy models. We attribute the success of simple effective models in physics as likewise emerging from complicated processes exhibiting a low effective dimensionality. We discuss the ramifications and consequences of sloppy models for biochemistry and science more generally. We suggest that the reason our complex world is understandable is due to the same fundamental reason: simple theories of macroscopic behavior are hidden inside complicated microscopic processes. PMID- 26156452 TI - Virtual CT morphometry of lower limb long bones for estimation of the sex and stature using postmortem Japanese adult data in forensic identification. AB - The application of computed tomography (CT) is useful for the documentation of whole-body anatomical data on routine autopsy, virtual reconstruction of skeletal structure, objective measurements, and reassessment by repetitive analyses. In addition, CT data processing facilitates volumetric and radiographic density analyses. Furthermore, a recently developed automated analysis system markedly improved the performance and accuracy of three-dimensional (3D) reconstruction. The present study investigated virtual CT morphometry of lower limb long bones, including the femur, tibia, fibula, and first metatarsus, to estimate the sex and stature using postmortem CT data of forensic autopsy cases of Japanese over 19 years of age (total n = 259, 150 males and 109 females). Bone mass volumes, lengths, and total CT attenuation values of bilateral femurs, tibias, and fibulas correlated with the stature; however, the mean CT attenuation (HU) values showed age-dependent decreases. Correlations with the stature were similar for the lengths and mass volumes of the femur, tibia, and fibula (r = 0.77-0.85) but were higher for the mass volume of the first metatarsus (r = 0.77 for right and r = 0.58 for left). In addition, the ratio of the bone volume to the length of each bone showed the most significant sex-related differences (males > females with accuracy of 75.8-98.1 %). These findings indicate the usefulness of virtual CT morphometry of individual lower limb long bones, including volumetry, to estimate the sex and stature in identification. PMID- 26156456 TI - Communication: spin densities within a unitary group based spin-adapted open shell coupled-cluster theory: analytic evaluation of isotropic hyperfine-coupling constants for the combinatoric open-shell coupled-cluster scheme. AB - We report analytical calculations of isotropic hyperfine-coupling constants in radicals using a spin-adapted open-shell coupled-cluster theory, namely, the unitary group based combinatoric open-shell coupled-cluster (COSCC) approach within the singles and doubles approximation. A scheme for the evaluation of the one-particle spin-density matrix required in these calculations is outlined within the spin-free formulation of the COSCC approach. In this scheme, the one particle spin-density matrix for an open-shell state with spin S and MS = + S is expressed in terms of the one- and two-particle spin-free (charge) density matrices obtained from the Lagrangian formulation that is used for calculating the analytic first derivatives of the energy. Benchmark calculations are presented for NO, NCO, CH2CN, and two conjugated pi-radicals, viz., allyl and 1 pyrrolyl in order to demonstrate the performance of the proposed scheme. PMID- 26156457 TI - Communication: structural interconversions between principal clathrate hydrate structures. AB - Gas clathrate hydrates formed with most gases belong to three common and well characterized crystalline structures known as sI, sII, and sH, although molecular mechanisms for their structural interconversions have remained poorly understood. Here, we present potential mechanisms for the interconversions between sI and sH and sII and sH, as observed within molecular simulations of the cross-nucleation of different methane hydrate phases. We find that a 4(1)5(10)6(2) cage intermediates the structural interconversion between sI and sH, while a sII crystal can form on a sH template directly. These structural interconversion pathways emphasize the diversity of possible clathrate hydrate phases characterized by a variety of tetrahedrally hydrogen-bonded structures. PMID- 26156458 TI - Communication: molecular dynamics and (1)H NMR of n-hexane in liquid crystals. AB - The NMR spectrum of n-hexane orientationally ordered in the nematic liquid crystal ZLI-1132 is analysed using covariance matrix adaptation evolution strategy (CMA-ES). The spectrum contains over 150 000 transitions, with many sharp features appearing above a broad, underlying background signal that results from the plethora of overlapping transitions from the n-hexane as well as from the liquid crystal. The CMA-ES requires initial search ranges for NMR spectral parameters, notably the direct dipolar couplings. Several sets of such ranges were utilized, including three from MD simulations and others from the modified chord model that is specifically designed to predict hydrocarbon-chain dipolar couplings. In the end, only inaccurate dipolar couplings from an earlier study utilizing proton-proton double quantum 2D-NMR techniques on partially deuterated n-hexane provided the necessary estimates. The precise set of dipolar couplings obtained can now be used to investigate conformational averaging of n-hexane in a nematic environment. PMID- 26156459 TI - Transport dissipative particle dynamics model for mesoscopic advection-diffusion reaction problems. AB - We present a transport dissipative particle dynamics (tDPD) model for simulating mesoscopic problems involving advection-diffusion-reaction (ADR) processes, along with a methodology for implementation of the correct Dirichlet and Neumann boundary conditions in tDPD simulations. tDPD is an extension of the classic dissipative particle dynamics (DPD) framework with extra variables for describing the evolution of concentration fields. The transport of concentration is modeled by a Fickian flux and a random flux between tDPD particles, and the advection is implicitly considered by the movements of these Lagrangian particles. An analytical formula is proposed to relate the tDPD parameters to the effective diffusion coefficient. To validate the present tDPD model and the boundary conditions, we perform three tDPD simulations of one-dimensional diffusion with different boundary conditions, and the results show excellent agreement with the theoretical solutions. We also performed two-dimensional simulations of ADR systems and the tDPD simulations agree well with the results obtained by the spectral element method. Finally, we present an application of the tDPD model to the dynamic process of blood coagulation involving 25 reacting species in order to demonstrate the potential of tDPD in simulating biological dynamics at the mesoscale. We find that the tDPD solution of this comprehensive 25-species coagulation model is only twice as computationally expensive as the conventional DPD simulation of the hydrodynamics only, which is a significant advantage over available continuum solvers. PMID- 26156460 TI - Solvent effects in the helix-coil transition model can explain the unusual biophysics of intrinsically disordered proteins. AB - We analyze a model statistical description of the polypeptide chain helix-coil transition, where we take into account the specificity of its primary sequence, as quantified by the phase space volume ratio of the number of all accessible states to the number corresponding to a helical conformation. The resulting transition phase diagram is then juxtaposed with the unusual behavior of the secondary structures in Intrinsically Disordered Proteins (IDPs) and a number of similarities are observed, even if the protein folding is a more complex transition than the helix-coil transition. In fact, the deficit in bulky and hydrophobic amino acids observed in IDPs, translated into larger values of phase space volume, allows us to locate the region in parameter space of the helix-coil transition that would correspond to the secondary structure transformations that are intrinsic to conformational transitions in IDPs and that is characterized by a modified phase diagram when compared to globular proteins. Here, we argue how the nature of this modified phase diagram, obtained from a model of the helix coil transition in a solvent, would illuminate the turned-out response of IDPs to the changes in the environment conditions that follow straightforwardly from the re-entrant (cold denaturation) branch in their folding phase diagram. PMID- 26156461 TI - A hybrid framework of first principles molecular orbital calculations and a three dimensional integral equation theory for molecular liquids: multi-center molecular Ornstein-Zernike self-consistent field approach. AB - In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl(-) + CH3Cl -> ClCH3 + Cl(-)) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF. PMID- 26156462 TI - An integral equation theory for solvation effects on the molecular structural fluctuation. AB - A new integral equation theory is proposed, which enables us to efficiently compute conformational distribution of a polyatomic molecule in solution phase. The solvation effect on the intramolecular correlation function is evaluated through a self-consistent procedure. In addition, the analytical expression of solvation free energy is derived, explicitly taking into account the molecular structural fluctuation. The derived equation establishes a direct route between the structural fluctuation and free energy of the molecule. The method was successfully applied to a series of n-alkanes in aqueous solutions to demonstrate the superiority of the proposed theory. PMID- 26156463 TI - Automatic differentiation method for numerical construction of the rotational vibrational Hamiltonian as a power series in the curvilinear internal coordinates using the Eckart frame. AB - We present a new numerical method to construct a rotational-vibrational Hamiltonian of a general polyatomic molecule in the Eckart frame as a power series expansion in terms of curvilinear internal coordinates. The expansion of the kinetic energy operator of an arbitrary order is obtained numerically using an automatic differentiation (AD) technique. The method is applicable to molecules of arbitrary size and structure and is flexible for choosing various types of internal coordinates. A new way of solving the Eckart-frame equations for curvilinear coordinates also based on the AD technique is presented. The resulting accuracy of the high-order expansion coefficients for the kinetic energy operator using our numerical technique is comparable to that obtained by symbolic differentiation, with the advantage of being faster and less demanding in memory. Examples for H2CO, NH3, PH3, and CH3Cl molecules demonstrate the advantages of the curvilinear internal coordinates and the Eckart molecular frame for accurate ro-vibrational calculations. Our results show that very high accuracy and quick convergence can be achieved even with moderate expansions if curvilinear coordinates are employed, which is important for applications involving large polyatomic molecules. PMID- 26156464 TI - Orbitals with intermediate localization and low coupling: spanning the gap between canonical and localized orbitals. AB - Localized orbitals are representations of electronic structure, which are easier to interpret than delocalized, canonical orbitals. While unitary transformations from canonical orbitals into localized orbitals have long been known, existing techniques maximize localization without regard to coupling between orbitals. Especially in conjugated pi spaces, orbitals are collapsed by unitary localization procedures into nonintuitive, strongly interacting units. Over localization decreases interpretability, results in large values of interorbital coupling, and gives unmeaningful diagonal Fock energies. Herein, we introduce orbitals of intermediate localization that span between canonical and fully localized orbitals. To within a specified error, these orbitals preserve the diagonal nature of the Fock matrix while still introducing significant locality. In systems composed of molecular fragments, pi spaces can be localized into weakly coupled units. Importantly, as the weakly coupled orbitals separate, highly coupled orbitals maintain their expected structure. The resulting orbitals therefore correspond well to chemical intuition and maintain accurate orbital energies, making this procedure unique among existing orbital localization techniques. This article focuses on the formation and physical analysis of orbitals that smoothly connect the known fully delocalized and fully localized limits. PMID- 26156465 TI - Wave packet propagation across barriers by semiclassical initial value methods. AB - Semiclassical initial value representation (IVR) formulas for the propagator have difficulty describing tunneling through barriers. A key reason is that these formulas do not automatically reduce, in the classical limit, to the version of the Van Vleck-Gutzwiller (VVG) propagator required to treat barrier tunneling, which involves trajectories that have complex initial conditions and that follow paths in complex time. In this work, a simple IVR expression, that has the correct tunneling form in the classical limit, is derived for the propagator in the case of one-dimensional barrier transmission. Similarly, an IVR formula, that reduces to the Generalized Gaussian Wave Packet Dynamics (GGWPD) expression [D. Huber, E. J. Heller, and R. Littlejohn, J. Chem. Phys. 89, 2003 (1988)] in the classical limit, is derived for the transmitted wave packet. Uniform semiclassical versions of the IVR formulas are presented and simplified expressions in terms of real trajectories and WKB penetration factors are described. Numerical tests show that the uniform IVR treatment gives good results for wave packet transmission through the Eckart and Gaussian barriers in all cases examined. In contrast, even when applied with the proper complex trajectories, the VVG and GGWPD treatments are inaccurate when the mean energy of the wave packet is near the classical transmission threshold. The IVR expressions for the propagator and wave packet are cast as contour integrals in the complex space of initial conditions and these are generalized to potentially allow treatment of a larger variety of systems. A steepest descent analysis of the contour integral formula for the wave packet in the present cases confirms its relationship to the GGWPD method, verifies its semiclassical validity, and explains results of numerical calculations. PMID- 26156467 TI - Direct summation of dipole-dipole interactions using the Wolf formalism. AB - We present an expanded Wolf formalism for direct summation of long-range dipole dipole interactions and rule-of-thumbs how to choose optimal spherical cutoff (Rc) and damping parameter (alpha). This is done by comparing liquid radial distribution functions, dipole-dipole orientation correlations, particle energies, and dielectric constants, with Ewald sums and the Reaction field method. The resulting rule states that alphasigma < 1 and alphaRc > 3 for reduced densities around rho(*) = 1 where sigma is the particle size. Being a pair potential, the presented approach scales linearly with system size and is applicable to simulations involving point dipoles such as the Stockmayer fluid and polarizable water models. PMID- 26156466 TI - Self-consistent description of electrokinetic phenomena in particle-based simulations. AB - A new computational method is presented for study suspensions of charged particles undergoing fluctuating hydrodynamic and electrostatic interactions. The proposed model is appropriate for polymers, proteins, and porous particles embedded in a continuum electrolyte. A self-consistent Langevin description of the particles is adopted in which hydrodynamic and electrostatic interactions are included through a Green's function formalism. An Ewald-like split is adopted in order to satisfy arbitrary boundary conditions for the Stokeslet and Poisson Green functions, thereby providing a formalism that is applicable to any geometry and that can be extended to deformable objects. The convection-diffusion equation for the continuum ions is solved simultaneously considering Nernst-Planck diffusion. The method can be applied to systems at equilibrium and far from equilibrium. Its applicability is demonstrated in the context of electrokinetic motion, where it is shown that the ionic clouds associated with individual particles can be severely altered by the flow and concentration, leading to intriguing cooperative effects. PMID- 26156468 TI - A hybrid molecular dynamics/fluctuating hydrodynamics method for modelling liquids at multiple scales in space and time. AB - A new 3D implementation of a hybrid model based on the analogy with two-phase hydrodynamics has been developed for the simulation of liquids at microscale. The idea of the method is to smoothly combine the atomistic description in the molecular dynamics zone with the Landau-Lifshitz fluctuating hydrodynamics representation in the rest of the system in the framework of macroscopic conservation laws through the use of a single "zoom-in" user-defined function s that has the meaning of a partial concentration in the two-phase analogy model. In comparison with our previous works, the implementation has been extended to full 3D simulations for a range of atomistic models in GROMACS from argon to water in equilibrium conditions with a constant or a spatially variable function s. Preliminary results of simulating the diffusion of a small peptide in water are also reported. PMID- 26156469 TI - Analytic first derivatives of floating occupation molecular orbital-complete active space configuration interaction on graphical processing units. AB - The floating occupation molecular orbital-complete active space configuration interaction (FOMO-CASCI) method is a promising alternative to the state-averaged complete active space self-consistent field (SA-CASSCF) method. We have formulated the analytic first derivative of FOMO-CASCI in a manner that is well suited for a highly efficient implementation using graphical processing units (GPUs). Using this implementation, we demonstrate that FOMO-CASCI gradients are of similar computational expense to configuration interaction singles (CIS) or time-dependent density functional theory (TDDFT). In contrast to CIS and TDDFT, FOMO-CASCI can describe multireference character of the electronic wavefunction. We show that FOMO-CASCI compares very favorably to SA-CASSCF in its ability to describe molecular geometries and potential energy surfaces around minimum energy conical intersections. Finally, we apply FOMO-CASCI to the excited state hydrogen transfer reaction in methyl salicylate. PMID- 26156470 TI - First assembly times and equilibration in stochastic coagulation-fragmentation. AB - We develop a fully stochastic theory for coagulation and fragmentation (CF) in a finite system with a maximum cluster size constraint. The process is modeled using a high-dimensional master equation for the probabilities of cluster configurations. For certain realizations of total mass and maximum cluster sizes, we find exact analytical results for the expected equilibrium cluster distributions. If coagulation is fast relative to fragmentation and if the total system mass is indivisible by the mass of the largest allowed cluster, we find a mean cluster-size distribution that is strikingly broader than that predicted by the corresponding mass-action equations. Combinations of total mass and maximum cluster size under which equilibration is accelerated, eluding late-stage coarsening, are also delineated. Finally, we compute the mean time it takes particles to first assemble into a maximum-sized cluster. Through careful state space enumeration, the scaling of mean assembly times is derived for all combinations of total mass and maximum cluster size. We find that CF accelerates assembly relative to monomer kinetic only in special cases. All of our results hold in the infinite system limit and can be only derived from a high-dimensional discrete stochastic model, highlighting how classical mass-action models of self assembly can fail. PMID- 26156471 TI - Polaron dynamics with a multitude of Davydov D2 trial states. AB - We propose an extension to the Davydov D2 Ansatz in the dynamics study of the Holstein molecular crystal model with diagonal and off-diagonal exciton-phonon coupling using the Dirac-Frenkel time-dependent variational principle. The new trial state by the name of the "multi-D2 Ansatz" is a linear combination of Davydov D2 trial states, and its validity is carefully examined by quantifying how faithfully it follows the Schrodinger equation. Considerable improvements in accuracy have been demonstrated in comparison with the usual Davydov trial states, i.e., the single D1 and D2 Ansatze. With an increase in the number of the Davydov D2 trial states in the multi-D2 Ansatz, deviation from the exact Schrodinger dynamics is gradually diminished, leading to a numerically exact solution to the Schrodinger equation. PMID- 26156472 TI - Efficient implementation of effective core potential integrals and gradients on graphical processing units. AB - Effective core potential integral and gradient evaluations are accelerated via implementation on graphical processing units (GPUs). Two simple formulas are proposed to estimate the upper bounds of the integrals, and these are used for screening. A sorting strategy is designed to balance the workload between GPU threads properly. Significant improvements in performance and reduced scaling with system size are observed when combining the screening and sorting methods, and the calculations are highly efficient for systems containing up to 10 000 basis functions. The GPU implementation preserves the precision of the calculation; the ground state Hartree-Fock energy achieves good accuracy for CdSe and ZnTe nanocrystals, and energy is well conserved in ab initio molecular dynamics simulations. PMID- 26156473 TI - Non-adiabatic molecular dynamics by accelerated semiclassical Monte Carlo. AB - Non-adiabatic dynamics, where systems non-radiatively transition between electronic states, plays a crucial role in many photo-physical processes, such as fluorescence, phosphorescence, and photoisomerization. Methods for the simulation of non-adiabatic dynamics are typically either numerically impractical, highly complex, or based on approximations which can result in failure for even simple systems. Recently, the Semiclassical Monte Carlo (SCMC) approach was developed in an attempt to combine the accuracy of rigorous semiclassical methods with the efficiency and simplicity of widely used surface hopping methods. However, while SCMC was found to be more efficient than other semiclassical methods, it is not yet as efficient as is needed to be used for large molecular systems. Here, we have developed two new methods: the accelerated-SCMC and the accelerated-SCMC with re-Gaussianization, which reduce the cost of the SCMC algorithm up to two orders of magnitude for certain systems. In most cases shown here, the new procedures are nearly as efficient as the commonly used surface hopping schemes, with little to no loss of accuracy. This implies that these modified SCMC algorithms will be of practical numerical solutions for simulating non-adiabatic dynamics in realistic molecular systems. PMID- 26156474 TI - Parametric sensitivity analysis for stochastic molecular systems using information theoretic metrics. AB - In this paper, we present a parametric sensitivity analysis (SA) methodology for continuous time and continuous space Markov processes represented by stochastic differential equations. Particularly, we focus on stochastic molecular dynamics as described by the Langevin equation. The utilized SA method is based on the computation of the information-theoretic (and thermodynamic) quantity of relative entropy rate (RER) and the associated Fisher information matrix (FIM) between path distributions, and it is an extension of the work proposed by Y. Pantazis and M. A. Katsoulakis [J. Chem. Phys. 138, 054115 (2013)]. A major advantage of the pathwise SA method is that both RER and pathwise FIM depend only on averages of the force field; therefore, they are tractable and computable as ergodic averages from a single run of the molecular dynamics simulation both in equilibrium and in non-equilibrium steady state regimes. We validate the performance of the extended SA method to two different molecular stochastic systems, a standard Lennard-Jones fluid and an all-atom methane liquid, and compare the obtained parameter sensitivities with parameter sensitivities on three popular and well-studied observable functions, namely, the radial distribution function, the mean squared displacement, and the pressure. Results show that the RER-based sensitivities are highly correlated with the observable based sensitivities. PMID- 26156475 TI - General criteria for determining rotation or oscillation in a two-dimensional axisymmetric system. AB - A self-propelled particle in a two-dimensional axisymmetric system, such as a particle in a central force field or confined in a circular region, may show rotational or oscillatory motion. These motions do not require asymmetry of the particle or the boundary, but arise through spontaneous symmetry breaking. We propose a generic model for a self-propelled particle in a two-dimensional axisymmetric system. A weakly nonlinear analysis establishes criteria for determining rotational or oscillatory motion. PMID- 26156476 TI - Complementary cavity-enhanced spectrometers to investigate the OH + CH combination band in trans-formic acid. AB - We have used continuous-wave cavity ring-down and femto-Fourier transform-cavity enhanced absorption spectrometers to record the spectrum of the OH-stretching + CH-stretching (nu1 + nu2) combination band in trans-formic acid, with origin close to 6507 cm(-1). They, respectively, allowed resolving and simplifying the rotational structure of the band near its origin under jet-cooled conditions (Trot = 10 K) and highlighting the overview of the band under room temperature conditions. The stronger B-type and weaker A-type subbands close to the band origin could be assigned, as well as the main B-type Q branches. The high resolution analysis was hindered by numerous, severe perturbations. Rotational constants are reported with, however, limited physical meaning. The nu1 + nu2 transition moment is estimated from relative intensities to be 24 degrees away from the principal b-axis of inertia. PMID- 26156477 TI - Analyses of bifurcation of reaction pathways on a global reaction route map: a case study of gold cluster Au5. AB - A global reaction route map is generated for Au5 by the anharmonic downward distortion following method in which 5 minima and 14 transition states (TSs) are located. Through vibrational analyses in the 3N - 7 (N = 5) dimensional space orthogonal to the intrinsic reaction coordinate (IRC), along all the IRCs, four IRCs are found to have valley-ridge transition (VRT) points on the way where a potential curvature changes its sign from positive to negative in a direction orthogonal to the IRC. The detailed mechanisms of bifurcations related to the VRTs are discussed by surveying a landscape of the global reaction route map, and the connectivity of VRT points and minima is clarified. Branching of the products through bifurcations is confirmed by ab initio molecular dynamics simulations starting from the TSs. A new feature of the reaction pathways, unification, is found and discussed. PMID- 26156478 TI - Excited-state dynamics of furan studied by sub-20-fs time-resolved photoelectron imaging using 159-nm pulses. AB - The excited-state dynamics of furan were studied by time-resolved photoelectron imaging using a sub-20-fs deep UV (198 nm) and vacuum UV (159 nm) light source. The 198- and 159-nm pulses produce photoionization signals in both pump-probe and probe-pump pulse sequences. When the 198-nm pulse precedes the 159-nm pulse, it creates the (1)A2(3s) Rydberg and (1)B2(pipi(*)) valence states, and the former decays exponentially with a time constant of about 20 fs whereas the latter exhibits more complex wave-packet dynamics. When the 159-nm pulse precedes the 198-nm pulse, a wave packet is created on the (1)A1(pipi(*)) valence state, which rapidly disappears from the observation window owing to structural deformation. The 159-nm photoexcitation also creates the 3s and 3px,y Rydberg states non adiabatically. PMID- 26156479 TI - Millimeter-wave spectroscopy of the FeCO radical in the nu2 and nu3 vibrationally excited states. AB - The pure rotational spectra of the FeCO radical in the nu2 (bending) and nu3 (Fe C stretching) vibrational states of the ground X(3)Sigma(-) electronic state were observed in the millimeter-wave region. The equilibrium rotational and centrifugal distortion constants were determined to be Be = 4374.631 (58) MHz and De = 1.1666 (20) kHz together with the spin-spin coupling constant lambdae = 691.89 (37) GHz and spin-rotation coupling constant gammae = - 1079.4 (55) MHz with use of the millimeter-wave results and the nu1 IR data. The equilibrium bond length for Fe-C was derived to be 1.725 A assuming that for C-O to be 1.159 A. Since the vibronic symmetry of the excited state of bending vibration is (3)Pi, the analysis of spectrum in the nu2 state required an effective spin-orbit interaction constant of A2 = 6.0219 (61) GHz together with three parity doubling constants of o2 = 36.168 (10) GHz, p2 = 85.18 (34) MHz, and q2 = 4.7024 (17) MHz. The effective spin-orbit interaction constant A2 is attributed to the vibronic mixing of the (3)Pi excited electronic states. The vibronic mixing also cause the parity doubling constants o2 and p2, but the main contribution to q2 is given by the vibrational l-type doubling. PMID- 26156480 TI - Structural evolution of the methane cation in subfemtosecond photodynamics. AB - An ab initio quantum dynamics study has been performed to explore the structural rearrangement of ground state CH4 (+) in subfemtosecond resolved photodynamics. The method utilizes time-dependent wave-packet propagation on the X~(2)T2 electronic manifold of the title cation in full dimensionality, including nonadiabatic coupling of the three electronic sheets. Good agreement is obtained with recent experiments [Baker et al., Science 312, 424 (2006)] which use high order harmonic generation to probe the attosecond proton dynamics. The novel results provide direct theoretical support of the observations while unravelling the underlying details. With the geometrical changes obtained by calculating the expectation values of the nuclear coordinates as a function of time, the structural evolution is predicted to begin through activation of the totally symmetric a1 and doubly degenerate e modes. While the former retains the original Td symmetry of the cation, the Jahn-Teller active e mode conducts it to a D2d structure. At ~1.85 fs, the intermediate D2d structure is further predicted to rearrange to local C2v minimum geometry via Jahn-Teller active bending vibrations of t2 symmetry. PMID- 26156481 TI - Photodissociation of D2 (+) induced by linearly chirped laser pulses. AB - Recently, it has been revealed that so-called light-induced conical intersections (LICIs) can be formed both by standing or by running laser waves even in diatomic molecules. Due to the strong nonadiabatic couplings, the existence of such LICIs has significant impact on the dynamical properties of a molecular system. In our former studies, the photodissociation process of the D2 (+) molecule was studied initiating the nuclear dynamics both from individual vibrational levels and from the superposition of all the vibrational states produced by ionizing D2. In the present work, linearly chirped laser pulses were used for initiating the dissociation dynamics of D2 (+). In contrast to the constant frequency (transform limited) laser fields, the chirped pulses give rise to LICIs with a varying position according to the temporal frequency change. To demonstrate the impact of these LICIs on the dynamical properties of diatomics, the kinetic energy release spectra, the total dissociation probabilities, and the angular distributions of the D2 (+) photofragments were calculated and discussed. PMID- 26156482 TI - A modified two-state empirical valence bond model for proton transport in aqueous solutions. AB - A detailed analysis of the proton solvation structure and transport properties in aqueous solutions is performed using classical molecular dynamics simulations. A refined two-state empirical valence bond (aTS-EVB) method, which is based on the EVB model of Walbran and Kornyshev and the anharmonic water force field, is developed in order to describe efficiently excess proton transport via the Grotthuss mechanism. The new aTS-EVB model clearly satisfies the requirement for simpler and faster calculation, because of the simplicity of the two-state EVB algorithm, while providing a better description of diffusive dynamics of the excess proton and water in comparison with the previous two-state EVB models, which significantly improves agreement with the available experimental data. The results of activation energies for the excess proton and water calculated between 300 and 340 K (the temperature range used in this study) are also found to be in good agreement with the corresponding experimental data. PMID- 26156483 TI - IR and SFG vibrational spectroscopy of the water bend in the bulk liquid and at the liquid-vapor interface, respectively. AB - Vibrational spectroscopy of the water bending mode has been investigated experimentally to study the structure of water in condensed phases. In the present work, we calculate the theoretical infrared (IR) and sum-frequency generation (SFG) spectra of the HOH bend in liquid water and at the water liquid/vapor interface using a mixed quantum/classical approach. Classical molecular dynamics simulation is performed by using a recently developed water model that explicitly includes three-body interactions and yields a better description of the water surface. Ab-initio-based transition frequency, dipole, polarizability, and intermolecular coupling maps are developed for the spectral calculations. The calculated IR and SFG spectra show good agreement with the experimental measurements. In the theoretical imaginary part of the SFG susceptibility for the water liquid/vapor interface, we find two features: a negative band centered at 1615 cm(-1) and a positive band centered at 1670 cm( 1). We analyze this spectrum in terms of the contributions from molecules in different hydrogen-bond classes to the SFG spectral density and also compare to SFG results for the OH stretch. SFG of the water bending mode provides a complementary picture of the heterogeneous hydrogen-bond configurations at the water surface. PMID- 26156484 TI - Mixed quantum/classical approach to OH-stretch inelastic incoherent neutron scattering spectroscopy for ambient and supercooled liquid water and ice Ih. AB - OH-stretch inelastic incoherent neutron scattering (IINS) has been measured to determine the vibrational density of states (VDOS) in the OH-stretch region for liquid water, supercooled water, and ice Ih, providing complementary information to IR and Raman spectroscopies about hydrogen bonding in these phases. In this work, we extend the combined electronic-structure/molecular-dynamics (ES/MD) method, originally developed by Skinner and co-workers to simulate OH-stretch IR and Raman spectra, to the calculation of IINS spectra with small k values. The agreement between theory and experiment in the limit k -> 0 is reasonable, further validating the reliability of the ES/MD method in simulating OH-stretch spectroscopy in condensed phases. The connections and differences between IINS and IR spectra are analyzed to illustrate the advantages of IINS over IR in estimating the OH-stretch VDOS. PMID- 26156486 TI - Line-tension-induced scenario of heterogeneous nucleation on a spherical substrate and in a spherical cavity. AB - Line-tension-induced scenario of heterogeneous nucleation is studied for a lens shaped nucleus with a finite contact angle nucleated on a spherical substrate and on the bottom of the wall of a spherical cavity. The effect of line tension on the free energy of a critical nucleus can be separated from the usual volume term. By comparing the free energy of a lens-shaped critical nucleus of a finite contact angle with that of a spherical nucleus, we find that a spherical nucleus may have a lower free energy than a lens-shaped nucleus when the line tension is positive and large, which is similar to the drying transition predicted by Widom [B. Widom, J. Phys. Chem. 99, 2803 (1995)]. Then, the homogeneous nucleation rather than the heterogeneous nucleation will be favorable. Similarly, the free energy of a lens-shaped nucleus becomes negative when the line tension is negative and large. Then, the barrier-less nucleation with no thermal activation called athermal nucleation will be realized. PMID- 26156485 TI - United polarizable multipole water model for molecular mechanics simulation. AB - We report the development of a united AMOEBA (uAMOEBA) polarizable water model, which is computationally 3-5 times more efficient than the three-site AMOEBA03 model in molecular dynamics simulations while providing comparable accuracy for gas-phase and liquid properties. In this coarse-grained polarizable water model, both electrostatic (permanent and induced) and van der Waals representations have been reduced to a single site located at the oxygen atom. The permanent charge distribution is described via the molecular dipole and quadrupole moments and the many-body polarization via an isotropic molecular polarizability, all located at the oxygen center. Similarly, a single van der Waals interaction site is used for each water molecule. Hydrogen atoms are retained only for the purpose of defining local frames for the molecular multipole moments and intramolecular vibrational modes. The parameters have been derived based on a combination of ab initio quantum mechanical and experimental data set containing gas-phase cluster structures and energies, and liquid thermodynamic properties. For validation, additional properties including dimer interaction energy, liquid structures, self diffusion coefficient, and shear viscosity have been evaluated. The results demonstrate good transferability from the gas to the liquid phase over a wide range of temperatures, and from nonpolar to polar environments, due to the presence of molecular polarizability. The water coordination, hydrogen-bonding structure, and dynamic properties given by uAMOEBA are similar to those derived from the all-atom AMOEBA03 model and experiments. Thus, the current model is an accurate and efficient alternative for modeling water. PMID- 26156487 TI - Crystal growth kinetics in Lennard-Jones and Weeks-Chandler-Andersen systems along the solid-liquid coexistence line. AB - Kinetics of crystal-growth is investigated along the solid-liquid coexistence line for the (100), (110), and (111) orientations of the Lennard-Jones (LJ) and Weeks-Chandler-Andersen (WCA) fcc crystal-liquid interface, using non-equilibrium molecular dynamics simulations. A slowing down of the growth kinetics along the coexistence line is observed, which is due to the decrease of the melting enthalpy with increasing coexistence temperature and pressure. Other quantities such as the melting pressure and liquid self-diffusion coefficient have a comparatively lesser impact on the kinetic growth coefficient. Growth kinetics of the LJ and WCA potentials become similar at large values of the melting temperature and pressure, when both resemble a purely repulsive soft-sphere potential. Classical models of crystallization from the melt are in reasonable qualitative agreement with our simulation data. Finally, several one-phase empirical melting/freezing rules are studied with respect to their validity along the coexistence line. PMID- 26156488 TI - The molecular dynamics of adsorption and dissociation of O2 on Pt(553). AB - Molecular adsorption and dissociation of O2 on the stepped Pt(553) surface have been investigated using supersonic molecular beam techniques and temperature programmed desorption. The initial and coverage-dependent sticking probability was determined with the King and Wells technique for various combinations of incident kinetic energy, surface temperature, incident angle, and surface coverage. A comparison with similar data for Pt(533) and Pt{110}(1 * 2) shows quantitatively the same high step-induced sticking at low incident energies compared to Pt(111). The enhancement is therefore insensitive to the exact arrangement of atoms forming surface corrugation. We consider energy transfer and electronic effects to explain the enhanced sticking. On the other hand, dissociation dynamics at higher incident kinetic energies are strongly dependent on step type. The Pt(553) and Pt(533) surfaces are more reactive than Pt(111), but the (100) step shows higher sticking than the (110) step. We relate this difference to a variation in the effective lowering of the barrier to dissociation from molecularly adsorbed states into atomic states. Our findings are in line with results from experimental desorption studies and theoretical studies of atomic binding energies. We discuss the influence of the different step types on sticking and dissociation dynamics with a one-dimensional potential energy surface. PMID- 26156489 TI - Self-organization of S adatoms on Au(111): ?3R30 degrees rows at low coverage. AB - Using scanning tunneling microscopy, we observe an adlayer structure that is dominated by short rows of S atoms, on unreconstructed regions of a Au(111) surface. This structure forms upon adsorption of low S coverage (less than 0.1 monolayer) on a fully reconstructed clean surface at 300 K, then cooling to 5 K for observation. The rows adopt one of three orientations that are rotated by 30 degrees from the close-packed directions of the Au(111) substrate, and adjacent S atoms in the rows are separated by ?3 times the surface lattice constant, a. Monte Carlo simulations are performed on lattice-gas models, derived using a limited cluster expansion based on density functional theory energetics. Models which include long-range pairwise interactions (extending to 5a), plus selected trio interactions, successfully reproduce the linear rows of S atoms at reasonable temperatures. PMID- 26156490 TI - Quantum dynamical simulation of the scattering of Ar from a frozen LiF(100) surface based on a first principles interaction potential. AB - In-plane two and three dimensional diffraction patterns are computed for the vertical scattering of an Ar atom from a frozen LiF(100) surface. Suitable collimation of the incoming wavepacket serves to reveal the quantum mechanical diffraction. The interaction potential is based on a fit to an ab initio potential calculated using density functional theory with dispersion corrections. Due to the potential coupling found between the two horizontal surface directions, there are noticeable differences between the quantum angular distributions computed for two and three dimensional scattering. The quantum results are compared to analogous classical Wigner computations on the same surface and with the same conditions. The classical dynamics largely provides the envelope for the quantum diffractive scattering. The classical results also show that the corrugation along the [110] direction of the surface is smaller than along the [100] direction, in qualitative agreement with experimental observations of unimodal and bimodal scattering for the [110] and [100] directions, respectively. PMID- 26156491 TI - Molecular dynamics study on condensation/evaporation coefficients of chain molecules at liquid-vapor interface. AB - The structure and thermodynamic properties of the liquid-vapor interface are of fundamental interest for numerous technological implications. For simple molecules, e.g., argon and water, the molecular condensation/evaporation behavior depends strongly on their translational motion and the system temperature. Existing molecular dynamics (MD) results are consistent with the theoretical predictions based on the assumption that the liquid and vapor states in the vicinity of the liquid-vapor interface are isotropic. Additionally, similar molecular condensation/evaporation characteristics have been found for long-chain molecules, e.g., dodecane. It is unclear, however, whether the isotropic assumption is valid and whether the molecular orientation or the chain length of the molecules affects the condensation/evaporation behavior at the liquid-vapor interface. In this study, MD simulations were performed to study the molecular condensation/evaporation behavior of the straight-chain alkanes, i.e., butane, octane, and dodecane, at the liquid-vapor interface, and the effects of the molecular orientation and chain length were investigated in equilibrium systems. The results showed that the condensation/evaporation behavior of chain molecules primarily depends on the molecular translational energy and the surface temperature and is independent of the molecular chain length. Furthermore, the orientation at the liquid-vapor interface was disordered when the surface temperature was sufficiently higher than the triple point and had no significant effect on the molecular condensation/evaporation behavior. The validity of the isotropic assumption was confirmed, and we conclude that the condensation/evaporation coefficients can be predicted by the liquid-to-vapor translational length ratio, even for chain molecules. PMID- 26156493 TI - Hydration-dependent dynamics of human telomeric oligonucleotides in the picosecond timescale: a neutron scattering study. AB - The dynamics of the human oligonucleotide AG3(T2AG3)3 has been investigated by incoherent neutron scattering in the sub-nanosecond timescale. A hydration dependent dynamical activation of thermal fluctuations in weakly hydrated samples was found, similar to that of protein powders. The amplitudes of such thermal fluctuations were evaluated in two different exchanged wave-vector ranges, so as to single out the different contributions from intra- and inter-nucleotide dynamics. The activation energy was calculated from the temperature-dependent characteristic times of the corresponding dynamical processes. The trends of both amplitudes and activation energies support a picture where oligonucleotides possess a larger conformational flexibility than long DNA sequences. This additional flexibility, which likely results from a significant relative chain end contribution to the average chain dynamics, could be related to the strong structural polymorphism of the investigated oligonucleotides. PMID- 26156492 TI - Dynamic behaviors and transport properties of ethanol molecules in transmembrane cyclic peptide nanotubes. AB - Classical molecular dynamics simulations have been performed to investigate the dynamic behaviors and transport properties of ethanol molecules in transmembrane cyclic peptide nanotubes (CPNTs) with various radii, i.e., 8*(WL-)n=3,4,5/POPE. The results show that ethanol molecules spontaneously fill the octa- and deca CPNTs, but not the hexa-CPNT. In the octa-CPNT, ethanol molecules are trapped at individual gaps with their carbon skeletons perpendicular to the tube axis and hydroxyl groups towards the tube wall, forming a broken single-file chain. As the channel radius increases, ethanol molecules inside the deca-CPNT tend to form a tubular layer and the hydroxyl groups mainly stretch towards the tube axis. Computations of diffusion coefficients indicate that ethanol molecules in the octa-CPNT nearly lost their diffusion abilities, while those in the deca-CPNT diffuse as 4.5 times as in a (8, 8) carbon nanotube with a similar tube diameter. The osmotic and diffusion permeabilities (pf and pd, respectively) of the octa- and deca-CPNTs transporting ethanol were deduced for the first time. The distributions of the gauche and trans conformers of ethanol molecules in two CPNTs are quite similar, both with approximately 57% gauche conformers. The non bonded interactions of channel ethanol with a CPNT wall and surrounding ethanol were explored. The potential of mean force elucidates the mechanism underlying the transporting characteristics of channel ethanol in a transmembrane CPNT. PMID- 26156494 TI - Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: a combined experimental and theoretical study. AB - Experimental studies (circular dichroism and ultra-violet (UV) absorption spectra) and large scale atomistic molecular dynamics simulations (accompanied by order parameter analyses) are combined to establish a number of remarkable (and unforeseen) structural transformations of protein myoglobin in aqueous ethanol mixture at various ethanol concentrations. The following results are particularly striking. (1) Two well-defined structural regimes, one at xEtOH ~ 0.05 and the other at xEtOH ~ 0.25, characterized by formation of distinct partially folded conformations and separated by a unique partially unfolded intermediate state at xEtOH ~ 0.15, are identified. (2) Existence of non-monotonic composition dependence of (i) radius of gyration, (ii) long range contact order, (iii) residue specific solvent accessible surface area of tryptophan, and (iv) circular dichroism spectra and UV-absorption peaks are observed. Interestingly at xEtOH ~ 0.15, time averaged value of the contact order parameter of the protein reaches a minimum, implying that this conformational state can be identified as a molten globule state. Multiple structural transformations well known in water-ethanol binary mixture appear to have considerably stronger effects on conformation and dynamics of the protein. We compare the present results with studies in water dimethyl sulfoxide mixture where also distinct structural transformations are observed along with variation of co-solvent composition. PMID- 26156495 TI - A member of the HSP90 family from ovine Babesia in China: molecular characterization, phylogenetic analysis and antigenicity. AB - Heat shock protein 90 (HSP90) is a key component of the molecular chaperone complex essential for activating many signalling proteins involved in the development and progression of pathogenic cellular transformation. A Hsp90 gene (BQHsp90) was cloned and characterized from Babesia sp. BQ1 (Lintan), an ovine Babesia isolate belonging to Babesia motasi-like group, by screening a cDNA expression library and performing rapid amplification of cDNA ends. The full length cDNA of BQHsp90 is 2399 bp with an open reading frame of 2154 bp encoding a predicted 83 kDa polypeptide with 717 amino acid residues. It shows significant homology and similar structural characteristics to Hsp90 of other apicomplex organisms. Phylogenetic analysis, based on the HSP90 amino acid sequences, showed that the Babesia genus is clearly separated from other apicomplexa genera. Five Chinese ovine Babesia isolates were divided into 2 phylogenetic clusters, namely Babesia sp. Xinjiang (previously designated a new species) cluster and B. motasi like cluster which could be further divided into 2 subclusters (Babesia sp. BQ1 (Lintan)/Babesia sp. Tianzhu and Babesia sp. BQ1 (Ningxian)/Babesia sp. Hebei). Finally, the antigenicity of rBQHSP90 protein from prokaryotic expression was also evaluated using western blot and enzyme-linked immunosorbent assay (ELISA). PMID- 26156496 TI - Platelet endothelial aggregation receptor-1: a novel modifier of neoangiogenesis. AB - AIMS: Platelet endothelial aggregation receptor-1 (PEAR1) is a cell membrane protein, expressed on platelets and endothelial cells (ECs). PEAR1 sustains alphaIIbbeta3 activation in aggregating platelets and attenuates megakaryopoiesis via controlling the degree of Akt phosphorylation. Its role in EC biology is unknown. The aim of this study was to determine the expression of PEAR1 in the human endothelium of various tissues and to investigate its role in ECs in vitro and in angiogenesis, using Pear1(-/-) mice. METHODS AND RESULTS: PEAR1 is present on the membrane and on filo- and lamellipodia of human cultured ECs, and its expression coincides with CD31 in various tissues. PEAR1 expression is variable in ECs of different origin. Lentiviral knockdown of PEAR1 in cultured ECs doubled EC proliferation and significantly stimulated EC migration, in turn enhancing in vitro tube formation on matrigel through the Akt/PTEN-dependent p21/CDC2 pathway. Even when physiological blood vessel formation was unaffected in Pear1(-/-) mice, neoangiogenesis in these mice was significantly increased both in a hind limb ischaemia ligation model [4.7-fold increase in capillary density in the ligated limb of Pear1(-/-) mice compared with ligated limbs in wild-type (WT) mice] and in a skin wound-healing model, resulting in a two-fold faster wound closure in Pear1(-/-) mice compared with WT littermates. CONCLUSION: We established an inverse correlation between endothelial PEAR1 expression and vascular assembly both in vitro and in vivo. These findings identify PEAR1 as a novel modifier of neoangiogenesis. PMID- 26156497 TI - Extracellular component hyaluronic acid and its receptor Hmmr are required for epicardial EMT during heart regeneration. AB - AIMS: After injury, the adult zebrafish can regenerate the heart. This requires the activation of the endocardium and epicardium as well as the proliferation of pre-existing cardiomyocytes to replace the lost tissue. However, the molecular mechanisms involved in this process are not completely resolved. In this work, we aim to identify the proteins involved in zebrafish heart regeneration and to explore their function. METHODS AND RESULTS: Using a proteomic approach, we identified Hyaluronan-mediated motility receptor (Hmmr), a hyaluronic acid (HA) receptor, to be expressed following ventricular resection in zebrafish. Moreover, enzymes that produce HA, hyaluronic acid synthases (has), were also expressed following injury, suggesting that this pathway may serve important functions in the regenerating heart. Indeed, suppression of HA production, as well as depletion of Hmmr, blocked cardiac regeneration. Mechanistically, HA and Hmmr are required for epicardial cell epithelial-mesenchymal transition (EMT) and their subsequent migration into the regenerating ventricle. Furthermore, chemical inhibition of Focal Adhesion Kinase (FAK) or inhibition of Src kinases, downstream effectors of Hmmr, also prevented epicardial cell migration, implicating a HA/Hmmr/FAK/Src pathway in this process. In a rat model of myocardial infarction, both HA and HMMR were up-regulated and localized in the infarct area within the first few days following damage, suggesting that this pathway may also play an important role in cardiac repair in mammals. CONCLUSION: HA and Hmmr are required for activated epicardial cell EMT and migration involving the FAK/Src pathway for proper heart regeneration. PMID- 26156498 TI - Shox2 is required for the proper development of the facial motor nucleus and the establishment of the facial nerves. AB - BACKGROUND: Axons from the visceral motor neurons (vMNs) project from nuclei in the hindbrain to innervate autonomic ganglia and branchial arch-derived muscles. Although much is known about the events that govern specification of somatic motor neurons, the genetic pathways responsible for the development of vMNs are less well characterized. We know that vMNs, like all motor neurons, depend on sonic hedgehog signaling for their generation. Similarly, the paired-like homeobox 2b (Phox2b) gene, which is expressed in both proliferating progenitors and post-mitotic motor neurons, is essential for the development of vMNs. Given that our previous study identified a novel role for the short stature homeobox 2 (Shox2) gene in the hindbrain, and since SHOX2 has been shown to regulate transcription of islet 1 (Isl1), an important regulator of vMN development, we sought to determine whether Shox2 is required for the proper development of the facial motor nucleus. RESULTS: Using a Nestin-Cre driver, we show that elimination of Shox2 throughout the brain results in elevated cell death in the facial motor nucleus at embryonic day 12.5 (E12.5) and E14.5, which correlates with impaired axonal projection properties of vMNs. We also observed changes in the spatial expression of the vMN cell fate factors Isl1 and Phox2b, and concomitant defects in Shh and Ptch1 expression in Shox2 mutants. Furthermore, we demonstrate that elimination of Shox2 results in the loss of dorsomedial and ventromedial subnuclei by postnatal day 0 (P0), which may explain the changes in physical activity and impaired feeding/nursing behavior in Shox2 mutants. CONCLUSIONS: Combined, our data show that Shox2 is required for development of the facial motor nucleus and its associated facial (VII) nerves, and serves as a new molecular tool to probe the genetic programs of this understudied hindbrain region. PMID- 26156499 TI - Effects of dietary fatty acids on mitochondrial phospholipid compositions, oxidative status and mitochondrial gene expression of zebrafish at different ages. AB - Mitochondrial decay is generally associated with impairment in the organelle bioenergetics function and increased oxidative stress, and it appears that deterioration of mitochondrial inner membrane phospholipids (PL) and accumulation of mitochondrial DNA (mtDNA) mutations are among the main mechanisms involved in this process. In the present study, mitochondrial membrane PL compositions, oxidative status (TBARS content and SOD activity) and mtDNA gene expression of muscle and liver were analyzed in zebrafish fed two diets with lipid supplied either by rapeseed oil (RO) or a blend 60:40 of RO and DHA500 TG oil (DHA). Two feeding trials were performed using zebrafish from the same population of two ages (8 and 21 months). Dietary FA composition affected fish growth in 8-month old animals, which could be related to an increase in stress promoted by diet composition. Lipid peroxidation was considerably higher in mitochondria of 8 month-old zebrafish fed the DHA diet than in animals fed the RO diet. This could indicate higher oxidative damage to mitochondrial lipids, very likely due to increased incorporation of DHA in PL of mitochondrial membranes. Lipids would be among the first molecules affected by mitochondrial reactive oxygen species, and lipid peroxidation could propagate oxidative reactions that would damage other molecules, including mtDNA. Mitochondrial lipid peroxidation and gene expression of 21-month-old fish showed lower responsiveness to diet composition than those of younger fish. Differences found in the effect of diet composition on mitochondrial lipids between the two age groups could be indicating age-related changes in the ability to maintain structural homeostasis of mitochondrial membranes. PMID- 26156501 TI - An evaluation of statistical methods for DNA methylation microarray data analysis. AB - BACKGROUND: DNA methylation offers an excellent example for elucidating how epigenetic information affects gene expression. beta values and M values are commonly used to quantify DNA methylation. Statistical methods applicable to DNA methylation data analysis span a number of approaches such as Wilcoxon rank sum test, t-test, Kolmogorov-Smirnov test, permutation test, empirical Bayes method, and bump hunting method. Nonetheless, selection of an optimal statistical method can be challenging when different methods generate inconsistent results from the same data set. RESULTS: We compared six statistical approaches relevant to DNA methylation microarray analysis in terms of false discovery rate control, statistical power, and stability through simulation studies and real data examples. Observable differences were noticed between beta values and M values only when methylation levels were correlated across CpG loci. For small sample size (n=3 or 6 in each group), both the empirical Bayes and bump hunting methods showed appropriate FDR control and the highest power when methylation levels across CpG loci were independent. Only the bump hunting method showed appropriate FDR control and the highest power when methylation levels across CpG sites were correlated. For medium (n=12 in each group) and large sample sizes (n=24 in each group), all methods compared had similar power, except for the permutation test whenever the proportion of differentially methylated loci was low. For all sample sizes, the bump hunting method had the lowest stability in terms of standard deviation of total discoveries whenever the proportion of differentially methylated loci was large. The apparent test power comparisons based on raw p values from DNA methylation studies on ovarian cancer and rheumatoid arthritis provided results as consistent as those obtained in the simulation studies. Overall, these results provide guidance for optimal statistical methods selection under different scenarios. CONCLUSIONS: For DNA methylation studies with small sample size, the bump hunting method and the empirical Bayes method are recommended when DNA methylation levels across CpG loci are independent, while only the bump hunting method is recommended when DNA methylation levels are correlated across CpG loci. All methods are acceptable for medium or large sample sizes. PMID- 26156500 TI - Investigation into effects of antipsychotics on ectonucleotidase and adenosine deaminase in zebrafish brain. AB - Antipsychotic agents are used for the treatment of psychotic symptoms in patients with several brain disorders, such as schizophrenia. Atypical and typical antipsychotics differ regarding their clinical and side-effects profile. Haloperidol is a representative typical antipsychotic drug and has potent dopamine receptor antagonistic functions; however, atypical antipsychotics have been developed and characterized an important advance in the treatment of schizophrenia and other psychotic disorders. Purine nucleotides and nucleosides, such as ATP and adenosine, constitute a ubiquitous class of extracellular signaling molecules crucial for normal functioning of the nervous system. Indirect findings suggest that changes in the purinergic system, more specifically in adenosinergic activity, could be involved in the pathophysiology of schizophrenia. We investigated the effects of typical and atypical antipsychotics on ectonucleotidase and adenosine deaminase (ADA) activities, followed by an analysis of gene expression patterns in zebrafish brain. Haloperidol treatment (9 uM) was able to decrease ATP hydrolysis (35%), whereas there were no changes in hydrolysis of ADP and AMP in brain membranes after antipsychotic exposure. Adenosine deamination in membrane fractions was inhibited (38%) after haloperidol treatment when compared to the control; however, no changes were observed in ADA soluble fractions after haloperidol exposure. Sulpiride (250 uM) and olanzapine (100 uM) did not alter ectonucleotidase and ADA activities. Haloperidol also led to a decrease in entpd2_mq, entpd3 and adal mRNA transcripts. These findings demonstrate that haloperidol is an inhibitor of NTPDase and ADA activities in zebrafish brain, suggesting that purinergic signaling may also be a target of pharmacological effects promoted by this drug. PMID- 26156504 TI - Correction. PMID- 26156503 TI - Association of exposure to di-2-ethylhexylphthalate replacements with increased blood pressure in children and adolescents. AB - Phthalates are environmental chemicals widely used in consumer and personal care products. In this study, we examined associations of urinary phthalates with blood pressure, triglycerides, and lipoproteins in children and adolescents, performing a cross-sectional analysis of a subsample of US children 6 to 19 years of age who participated in the National Health and Nutrition Examination Survey between the years 2009 and 2012. We quantified exposure to common environmental phthalates, with a focus on the dietary contaminant di-2-ethylhexylphthalate and 2 increasingly used replacements, di-isononyl phthalate and di-isodecyl phthalate, based on micromolar concentration of urinary metabolites. We assessed descriptive, univariate, and multivariable associations with blood pressure and lipids. Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass, metabolites of di-2-ethylhexylphthalate, di-isononyl phthalate, and di-isodecyl phthalate were associated with higher age-, sex- and height-standardized blood pressure. For each log unit increase in di-isodecyl phthalate metabolites, a 0.105 standard deviation unit increase in systolic blood pressure z score was identified (P=0.004); for di-isononyl phthalate metabolites, a 0.113 standard deviation unit increment was identified (P=0.008). For di-2 ethylhexylphthalate metabolites, a 0.103 standard deviation unit increment (P=0.013) was detected. Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products showed an association with blood pressure (>=90th percentile) in univariate analysis, but this was no longer significant in our full multivariable model, suggesting specificity. Phthalate metabolites were not associated with triglycerides or high-density lipoproteins. Further, longitudinal studies are needed to confirm these associations and to assess opportunities for intervention. PMID- 26156505 TI - Correction. PMID- 26156507 TI - Animal extremists' threats to neurologic research continue: Neuroreality II. PMID- 26156506 TI - Long-term neuropsychiatric outcomes after pallidal stimulation in primary and secondary dystonia. AB - OBJECTIVE: To evaluate changes in the diagnosis of Axis I psychiatric disorders in patients with primary and secondary dystonia after deep brain stimulation (DBS) of the globus pallidus internus (GPi). METHODS: Structured Clinical Interviews for the DSM-IV, Axis I psychiatric disorders, were prospectively performed before and after surgery. Diagnoses were made based on DSM-IV criteria. Psychiatric disorders were grouped into 5 categories: mood, anxiety, addiction, obsessive-compulsive disorders, and psychosis. Patients could be stratified to more than one category. Rates for unchanged diagnoses, diagnoses in remission, and new-onset diagnoses after surgery for each category were calculated. RESULTS: Fifty-seven patients with primary and secondary dystonia were included. Mean +/- SD age at surgery and dystonia duration at time of surgery was 50.6 +/- 13.8 and 19.0 +/- 13.2 years, respectively. Preoperatively, 37 Axis I diagnoses were made in 25 patients, 43.8% of those presenting with at least 1 Axis I diagnosis (mostly mood and anxiety disorders). Mean +/- SD duration of psychiatric follow up was 24.4 +/- 19.6 months. Overall, after surgery no significant changes (p = 0.16) were found in Axis I diagnoses (23 patients, 40.3%): 27 (73%) unchanged, 10 (27%) in complete remission, and 4 (12.9%) new-onset diagnoses. CONCLUSIONS: Our results support the overall psychiatric stability of patients with primary and secondary dystonia treated with GPi DBS. However, considering the high psychiatric morbidity in the dystonia population, psychiatric assessments before and after surgery are strongly recommended. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that GPi DBS does not change Axis I psychiatric diagnoses in patients with primary and secondary dystonia. PMID- 26156508 TI - CSF leak: A complication from vomiting after magnetic vestibular stimulation. PMID- 26156509 TI - Decline of clinical research in academic medical centers. AB - Marked changes in US medical school funding began in the 1960s with progressively increasing revenues from clinical services. The growth of clinical revenues slowed in the mid-1990s, creating a funding crisis for US academic health care centers, who responded by having their faculty increase their clinical duties at the expense of research activities. Surveys document the resultant stresses on the academic clinician researcher. The NIH provides greater funding for basic and translational research than for clinical research, and the new Patient-Centered Outcomes Research Institute is inadequately funded to address the scope of needed clinical research. An increasing portion of clinical research is funded by industry, which leaves many important clinical issues unaddressed. There is an inadequate supply of skilled clinical researchers and a lack of external support for clinical research. The impact on the academic environment in university medical centers is especially severe on young faculty, who have a shrinking potential to achieve successful academic careers. National health care research funding policies should encourage the right balance of life-science investigations. Medical universities need to improve and highlight education on clinical research for students, residents, fellows, and young faculty. Medical universities also need to provide appropriate incentives for clinical research. Without training to ensure an adequate supply of skilled clinical researchers and a method to adequately fund clinical research, discoveries from basic and translational research cannot be clinically tested and affect patient care. Thus, many clinical problems will continue to be evaluated and treated with inadequate or even absent evidence-based knowledge. PMID- 26156510 TI - Aerobic exercise in muscular dystrophy: gain without pain. PMID- 26156511 TI - Effects of subthalamic nucleus stimulation on motor cortex plasticity in Parkinson disease. AB - OBJECTIVE: We hypothesized that subthalamic nucleus (STN) deep brain stimulation (DBS) will improve long-term potentiation (LTP)-like plasticity in motor cortex in Parkinson disease (PD). METHODS: We studied 8 patients with PD treated with STN-DBS and 9 age-matched healthy controls. Patients with PD were studied in 4 sessions in medication (Med) OFF/stimulator (Stim) OFF, Med-OFF/Stim-ON, Med ON/Stim-OFF, and Med-ON/Stim-ON states in random order. Motor evoked potential amplitude and cortical silent period duration were measured at baseline before paired associated stimulation (PAS) and at 3 different time intervals (T0, T30, T60) up to 60 minutes after PAS in the abductor pollicis brevis and abductor digiti minimi muscles. RESULTS: Motor evoked potential size significantly increased after PAS in controls (+67.7% of baseline at T30) and in patients in the Med-ON/Stim-ON condition (+55.8% of baseline at T30), but not in patients in the Med-OFF/Stim-OFF (-0.4% of baseline at T30), Med-OFF/Stim-ON (+10.3% of baseline at T30), and Med-ON/Stim-OFF conditions (+17.3% of baseline at T30). Cortical silent period duration increased after PAS in controls but not in patients in all test conditions. CONCLUSIONS: Our findings suggest that STN-DBS together with dopaminergic medications restore LTP-like plasticity in motor cortex in PD. Restoration of cortical plasticity may be one of the mechanisms of how STN-DBS produces clinical benefit. PMID- 26156512 TI - Aerobic training and postexercise protein in facioscapulohumeral muscular dystrophy: RCT study. AB - OBJECTIVE: To investigate the effect of regular aerobic training and postexercise protein-carbohydrate supplementation in patients with facioscapulohumeral muscular dystrophy (FSHD). METHODS: In this randomized, double-blind, placebo controlled parallel study, we randomized untrained men (n = 21) and women (n = 20) with FSHD (age 19-65 years) to 2 training groups-training with protein supplement (n = 18) and training with placebo supplement (n = 13)-and a nonintervention control group (n = 10). We assessed fitness, walking speed, muscle strength, questionnaires, and daily activity levels before and after 12 weeks of interventions. Training involved 36 sessions of 30-minute cycle ergometer training. After each session, patients drank either a protein carbohydrate or placebo beverage. RESULTS: In the trained participants, fitness, workload, and walking speed improved (10% [confidence interval (CI) 4%-15%], 18% [CI 10%-26%], 7% [CI 4%-11%], respectively, p < 0.001, number needed to treat = 2.1). Self-assessed physical capacity and health (Short Form-36) also improved. Muscle strength and daily activity levels did not change with training. Protein carbohydrate supplementation did not result in further improvements in any tests compared to training alone. CONCLUSIONS: This randomized, controlled study showed that regular endurance training improves fitness, walking speed, and self assessed health in patients with FSHD without causing muscle damage. Postexercise protein-carbohydrate supplementation does not add any further improvement to training effects alone. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that regular aerobic training with or without postexercise protein carbohydrate supplementation improves fitness and workload in patients with FSHD. PMID- 26156513 TI - Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes. AB - OBJECTIVE: The aim of this prospective study was to investigate the relationships between inflammation, cerebral vasoregulation, and cognitive decline in type 2 diabetes mellitus (T2DM) over a 2-year span. METHODS: Sixty-five participants (aged 66 +/- 9.2 years, 35 with T2DM, 33 women) were enrolled for this 2-year prospective study. Continuous arterial spin labeling at 3-tesla MRI was used to measure global and regional cerebral perfusion and vasoreactivity. Neuropsychological measures were evaluated at the beginning and completion of the study. The associations between serum inflammatory markers, regional cerebral vasoreactivity, and cognitive functions were examined using least squares models. RESULTS: After 2 years of follow-up, participants with T2DM had diminished global and regional cerebral vasoreactivity and a decline in multiple cognitive tasks compared with baseline (p < 0.0001-0.012). In the T2DM group, lower cerebral vasoreactivity was associated with a greater decrease in daily living activities score (r(2) adj = 0.35, p = 0.04), and lower global vasodilation was associated with a greater decline in executive function (r(2) adj = 0.6, p = 0.047). Higher serum soluble intercellular and vascular adhesion molecules, higher cortisol, and higher C-reactive protein levels at baseline were associated with greater decreases in cerebral vasoreactivity and vasodilation only in the T2DM group (r(2) adj = 0.16-0.53, p = 0.007-0.048), independent of diabetes control and 24 hour blood pressure. Higher glycated hemoglobin A1c levels were associated with a greater increase in vasoconstriction in the T2DM group. CONCLUSIONS: Inflammation may further impair cerebral vasoregulation, which consequently accelerates decline in executive function and daily activities performance in older people with T2DM. PMID- 26156514 TI - Cognitive correlates of white matter lesion load and brain atrophy: the Northern Manhattan Study. AB - OBJECTIVE: We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population. METHODS: We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates. RESULTS: MRI and cognitive data were available for 1,163 participants (mean age 70 +/- 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE epsilon4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function. CONCLUSIONS: In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance. PMID- 26156515 TI - Diabetes and cognitive decline in a French cohort of patients infected with HIV 1. AB - OBJECTIVE: We investigated the relationship of diabetes and prediabetes with cognitive performances, assessed through raw test and z scores and according to neurocognitive impairment (NCI) classification in a cohort of individuals infected with HIV. METHODS: The ANRS CO3 Aquitaine cohort is a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in 6 public hospitals in southwestern France. Between 2007 and 2009, an ancillary study consisted of a neuropsychological battery of 10 tests at baseline and 2-year follow-up. The severity of NCI (normal, asymptomatic, mild, HIV dementia) was assessed according to international guidelines. RESULTS: At baseline (400 patients, 33 with prediabetes, 39 with diabetes), in cross sectional multivariable analyses, patients with diabetes performed significantly worse on 9 neuropsychological tests that assessed memory, executive functions, attention, psychomotor speed, language, and manual dexterity. Participants with prediabetes had worse performances compared with those who had normal glycemia in 5 tests. The longitudinal analysis of the association between glycemia status at baseline and change in cognitive performances over 2-year follow-up (n = 283) suggested that patients with diabetes also showed a slightly higher decline on 5 of the 10 tests, those involving executive functions and memory functioning. Glycemia status at baseline was not significantly associated with NCI severity in cross-sectional (p = 0.44) and longitudinal (p = 0.64) analyses. CONCLUSIONS: In this hospital-based cohort of people living with HIV, diabetes, but not the other cardiovascular risk factors, is associated with worse cognitive performances in several cognitive domains and with larger decline in fewer domains over the short term. PMID- 26156516 TI - Light-Curing Units: A Review of What We Need to Know. AB - For improved interstudy reproducibility, reduced risk of premature failures, and ultimately better patient care, researchers and dentists need to know how to accurately characterize the electromagnetic radiation (light) they are delivering to the resins they are using. The output from a light-curing unit (LCU) is commonly characterized by its irradiance. If this value is measured at the light tip, it describes the radiant exitance from the surface of the light tip, and not the irradiance received by the specimen. The value quoted also reflects only an averaged value over the total measurement area and does not represent the irradiance that the resin specimen is receiving locally or at a different moment in time. Recent evidence has reported that the spectral emission and radiant exitance beam profiles from LCUs can be highly inhomogeneous. This can cause nonuniform temperature changes and uneven photopolymerization within the resin restoration. The spectral radiant power can be very different between different brands of LCUs, and the use of irradiance values derived from dental radiometers to describe the output from an LCU for research purposes is discouraged. Manufacturers should provide more information about the light output from the LCU and the absorption spectrum of their resin-based composite (RBC). Ideally, future assessments and research publications should include the following information about the curing light: 1) radiant power output throughout the exposure cycle and the spectral radiant power as a function of wavelength, 2) analysis of the light beam profile and spectral emission across the light beam, and 3) measurement and reporting of the light the RBC specimen received as well as the output measured at the light tip. PMID- 26156518 TI - Web Accessibility for Older Adults: A Comparative Analysis of Disability Laws. AB - Access to the Internet is increasingly critical for health information retrieval, access to certain government benefits and services, connectivity to friends and family members, and an array of commercial and social services that directly affect health. Yet older adults, particularly those with disabilities, are at risk of being left behind in this growing age- and disability-based digital divide. The Americans with Disabilities Act (ADA) was designed to guarantee older adults and persons with disabilities equal access to employment, retail, and other places of public accommodation. Yet older Internet users sometimes face challenges when they try to access the Internet because of disabilities associated with age. Current legal interpretations of the ADA, however, do not consider the Internet to be an entity covered by law. In this article, we examine the current state of Internet accessibility protection in the United States through the lens of the ADA, sections 504 and 508 of the Rehabilitation Act, state laws and industry guidelines. We then compare U.S. rules to those of OECD (Organisation for Economic Co-Operation and Development) countries, notably in the European Union, Canada, Japan, Australia, and the Nordic countries. Our policy recommendations follow from our analyses of these laws and guidelines, and we conclude that the biggest challenge in bridging the age- and disability-based digital divide is the need to extend accessibility requirements to private, not just governmental, entities and organizations. PMID- 26156517 TI - Exosomes in cancer: small particle, big player. AB - Exosomes have emerged as a novel mode of intercellular communication. Exosomes can shuttle bioactive molecules including proteins, DNA, mRNA, as well as non coding RNAs from one cell to another, leading to the exchange of genetic information and reprogramming of the recipient cells. Increasing evidence suggests that tumor cells release excessive amount of exosomes, which may influence tumor initiation, growth, progression, metastasis, and drug resistance. In addition, exosomes transfer message from tumor cells to immune cells and stromal cells, contributing to the escape from immune surveillance and the formation of tumor niche. In this review, we highlight the recent advances in the biology of exosomes as cancer communicasomes. We review the multifaceted roles of exosomes, the small secreted particles, in communicating with other cells within tumor microenvironment. Given that exosomes are cell type specific, stable, and accessible from body fluids, exosomes may provide promising biomarkers for cancer diagnosis and represent new targets for cancer therapy. PMID- 26156519 TI - Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports. AB - OBJECTIVE: To follow up on previously reported associations between periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and specific birth defects using an expanded dataset from the National Birth Defects Prevention Study. DESIGN: Bayesian analysis combining results from independent published analyses with data from a multicenter population based case-control study of birth defects. SETTING: 10 centers in the United States. PARTICIPANTS: 17,952 mothers of infants with birth defects and 9857 mothers of infants without birth defects, identified through birth certificates or birth hospitals, with estimated dates of delivery between 1997 and 2009. EXPOSURES: Citalopram, escitalopram, fluoxetine, paroxetine, or sertraline use in the month before through the third month of pregnancy. Posterior odds ratio estimates were adjusted to account for maternal race/ethnicity, education, smoking, and prepregnancy obesity. MAIN OUTCOME MEASURE: 14 birth defects categories that had associations with SSRIs reported in the literature. RESULTS: Sertraline was the most commonly reported SSRI, but none of the five previously reported birth defects associations with sertraline was confirmed. For nine previously reported associations between maternal SSRI use and birth defect in infants, findings were consistent with no association. High posterior odds ratios excluding the null value were observed for five birth defects with paroxetine (anencephaly 3.2, 95% credible interval 1.6 to 6.2; atrial septal defects 1.8, 1.1 to 3.0; right ventricular outflow tract obstruction defects 2.4, 1.4 to 3.9; gastroschisis 2.5, 1.2 to 4.8; and omphalocele 3.5, 1.3 to 8.0) and for two defects with fluoxetine (right ventricular outflow tract obstruction defects 2.0, 1.4 to 3.1 and craniosynostosis 1.9, 1.1 to 3.0). CONCLUSIONS: These data provide reassuring evidence for some SSRIs but suggest that some birth defects occur 2-3.5 times more frequently among the infants of women treated with paroxetine or fluoxetine early in pregnancy. PMID- 26156520 TI - Using gene expression signatures to identify novel treatment strategies in gulf war illness. AB - BACKGROUND: Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failure and a lengthy cycle time. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline. METHODS: Here, we explore drug re-purposing opportunities in GWI by combining systems biology and bioinformatics techniques with pharmacogenomic information to find overlapping elements in gene expression linking GWI to successfully treated diseases. Gene modules were defined based on cellular function and their activation estimated from the differential expression of each module's constituent genes. These gene modules were then cross-referenced with drug atlas and pharmacogenomic databases to identify agents currently used successfully for treatment in other diseases. To explore the clinical use of these drugs in illnesses similar to GWI we compared gene expression patterns in modules that were significantly expressed in GWI with expression patterns in those same modules in other illnesses. RESULTS: We found 19 functional modules with significantly altered gene expression patterns in GWI. Within these modules, 45 genes were documented drug targets. Illnesses with highly correlated gene expression patterns overlapping considerably with GWI were found in 18 of the disease conditions studied. Brain, muscular and autoimmune disorders composed the bulk of these. CONCLUSION: Of the associated drugs, immunosuppressants currently used in treating rheumatoid arthritis, and hormone based therapies were identified as the best available candidates for treating GWI symptoms. PMID- 26156522 TI - Efficacy of praziquantel against urinary schistosomiasis and reinfection in Senegalese school children where there is a single well-defined transmission period. AB - BACKGROUND: Human schistosomiasis is a significant health problem in Sub-Saharan Africa. In Niakhar, West central Senegal, the transmission of S. haematobium occurs seasonally between July and November. No control measures have been implemented despite high prevalence reported in previous studies. This aim of this study was to i) determine the current prevalence of S. haematobium in children at Niakhar, ii) assess the efficacy of one dose of PZQ (40 mg/kg) against S. haematobium and iii) monitor reinfection. METHODS: The current study was carried out in a cohort of 329 children aged five to 15 years enrolled from six villages in Niakhar to determine the efficacy of one dose of PZQ, as well as reinfection. Parasitological screening was performed in June 2011 to determine the baseline prevalence of S. haematobium, and then a single dose of PZQ was administered to all selected subjects in the transmission season in August 2011. The efficacy of PZQ treatment and reinfection were monitored respectively five weeks after in September 2011 and from February to March 2012. RESULTS: At baseline, the overall prevalence and the heavy intensity of infection were 73.2% and 356.1 eggs/10 ml of urine. Significant differences in the prevalence and intensity of S. haematobium infection were noted between villages. A single dose of PZQ significantly reduced the prevalence of S. haematobium infection from 73.2% to 4.6% and the geometric mean intensity of infection from 356.1 to 43.3 eggs/10 ml of urine. The cure rates ranged from 89.4% to 100%. The egg reduction rates also ranged from 77.6% to 100%. Two to three months after the period of transmission, the overall rate of reinfection was 12.6% and was significantly higher in male children than in female children. The overall prevalence at this period was 13.8%, which was significantly lower than the prevalence at baseline (73.2%). CONCLUSION: The Niakhar study area remains a hot spot of urinary schistosomiasis in Senegal with differences in transmission between villages. This study suggests that when transmission is strictly seasonal, Praziquantel shows the expected efficacy in reducing the prevalence and intensity of infection, but also a significant effect on the occurrence of reinfection. PMID- 26156521 TI - The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer. AB - BACKGROUND: Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. METHODS/DESIGN: The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. DISCUSSION: The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the potential of metabolomic profiles for risk assessment and early detection and the signalling pathways controlling the metastatic tumour microenvironment. There is substantial synergy between the four projects and it is hoped that this integrated program of research will advance our understanding of key aspects of bone metastases from breast cancer to improve the prevention, prediction, detection, and treatment of these lesions. PMID- 26156523 TI - Short-term enhancement effect of nitrogen addition on microbial degradation and plant uptake of polybrominated diphenyl ethers (PBDEs) in contaminated mangrove soil. AB - Effects of nitrogen (N) addition on the microbial degradation and uptake of a mixture of BDE-47 and -209 by Aegiceras corniculatum, a typical mangrove plant species were investigated. At the end of 3-month experiment, a significant dissipation of BDE-47 was observed in the planted soil, and this dissipation, particularly in rhizosphere soil, was significantly accelerated by the frequent addition of N in the form of ammonium chloride. The removal percentage of BDE-47 in the rhizosphere soil without N addition was 47.3% and increased to 58.2% with N. However, the unplanted soil only removed less than 25% BDE-47, irrespective to N supply. The N addition in planted treatments significantly increased soil N content, urease and dehydrogenase activities, and the abundances of total bacteria and dehalogenating bacteria, leading to more microbial degradation of BDE-47. The N addition also enhanced the root uptake and translocation of PBDEs to above-ground tissues of A. corniculatum. These results suggested that N addition could enhance the phytoremediation of BDE-47-contaminated soil within a short period of time. Different from BDE-47, BDE-209 in all contaminated soils was difficult to be removed due to its persistence and low bioavailability. PMID- 26156524 TI - Regulation rewiring analysis reveals mutual regulation between STAT1 and miR-155 5p in tumor immunosurveillance in seven major cancers. AB - Transcription factors (TFs) and microRNAs (miRNAs) form a gene regulatory network (GRN) at the transcriptional and post-transcriptional level in living cells. However, this network has not been well characterized, especially in regards to the mutual regulations between TFs and miRNAs in cancers. In this study, we collected those regulations inferred by ChIP-Seq or CLIP-Seq to construct the GRN formed by TFs, miRNAs, and target genes. To increase the reliability of the proposed network and examine the regulation activity of TFs and miRNAs, we further incorporated the mRNA and miRNA expression profiles in seven cancer types using The Cancer Genome Atlas data. We observed that regulation rewiring was prevalent during tumorigenesis and found that the rewired regulatory feedback loops formed by TFs and miRNAs were highly associated with cancer. Interestingly, we identified one regulatory feedback loop between STAT1 and miR-155-5p that is consistently activated in all seven cancer types with its function to regulate tumor-related biological processes. Our results provide insights on the losing equilibrium of the regulatory feedback loop between STAT1 and miR-155-5p influencing tumorigenesis. PMID- 26156525 TI - Screening for TB by sputum culture in high-risk groups in Copenhagen, Denmark: a novel and promising approach. AB - INTRODUCTION: Evidence on screening high-risk groups for TB by mobile X-ray in low-incidence countries is building, but knowledge on other possible screening methods is limited. In this retrospective study we report results from a community based programme screening for TB by spot sputum culture. METHODS: On seven occasions, from September 2012 through June 2014, we offered TB screening to all persons present at 11 locations where socially marginalised people gather in Copenhagen. Spot sputum samples from participants were examined by smear microscopy and culture. Genotype, nucleic acid amplification test and chest X-ray were done if TB was found. RESULTS: Among 1075 participants, we identified 36 cases of TB. Twenty-four cases (66.7%) were identified at the first screening of each participant, that is, the prevalence of TB was 2233/100 000. Thirty-five (97%) of the TB cases were culture-positive and seven (19.4%) were smear positive. Twelve out of 21 (57.1%) cases tested were nucleic acid amplification test positive. Twenty-eight (77.8%) had chest X-ray suggestive of TB. All patients with TB started treatment, 30 (83.3%) had a successful outcome. DISCUSSION: Screening for TB by spot sputum culture is possible and a promising alternative to mobile X-ray in a community based screening programme. 22.2% did not have chest X-ray suggestive of TB and would not have been identified using mobile X-ray. Most of the TB cases were smear-negative, suggesting that they were identified at an early, less infectious stage, which is essential in order to prevent transmission and gain infection control. PMID- 26156527 TI - Independent Association Between Improvement of Nonalcoholic Fatty Liver Disease and Reduced Incidence of Type 2 Diabetes. AB - OBJECTIVE: Only a few studies have evaluated the long-term effects of nonalcoholic fatty liver disease (NAFLD) on type 2 diabetes mellitus (T2DM), and none have examined whether NAFLD improvement reduces T2DM incidence. We investigated the association between NAFLD improvement and T2DM incidence. RESEARCH DESIGN AND METHODS: Between 2000 and 2012, 4,604 participants who underwent a health check twice with >10 years between were enrolled. Exclusion criteria were positive hepatitis B surface antigen, positive hepatitis C antibody, ethanol intake >20 g/day, and diabetes. The 3,074 eligible participants were divided into an NAFLD group (n = 728) and a non-NAFLD group (n = 2,346) according to ultrasonography-detected fatty liver. The NAFLD group was categorized into an improved group (n = 110) and a sustained NAFLD group (n = 618) based on fatty liver disappearance at the second visit. Incident T2DM odds ratios (ORs) were estimated by logistic regression models adjusted for age, sex, BMI, impaired fasting glucose, family history of diabetes, dyslipidemia, hypertension, and physical exercise. RESULTS: T2DM occurred in 117 participants (16.1%) in the NAFLD group and 72 (3.1%) in the non-NAFLD group. NAFLD at baseline was associated with T2DM incidence (multivariate OR 2.37 [95% CI 1.60 3.52]). T2DM occurred in 7 participants (6.4%) in the improved group and in 110 (17.8%) in the sustained NAFLD group. NAFLD improvement was associated with reduced T2DM incidence (multivariate OR 0.27 [95% CI 0.12-0.61]). CONCLUSIONS: NAFLD improvement is associated with T2DM incidence reduction. PMID- 26156526 TI - Objectively measured sleep characteristics and prevalence of coronary artery calcification: the Multi-Ethnic Study of Atherosclerosis Sleep study. AB - BACKGROUND: We tested whether objectively measured indices of obstructive sleep apnoea (OSA) and sleep quality are associated with coronary artery calcification (CAC) prevalence independent of obesity, a classic confounder. METHODS: 1465 Multi-Ethnic Study of Atherosclerosis participants (mean age 68 years), who were free of clinical cardiovascular disease, had both coronary CT and in-home polysomnography and actigraphy performed. OSA categories were defined by the Apnea-Hypopnea Index (AHI). Prevalence ratios (PRs) for CAC >0 and >400 (high burden) were calculated. RESULTS: Participants with severe OSA (AHI >=30; 14.6%) were more likely to have prevalent CAC, relative to those with no evidence of OSA, after adjustment for demographics and smoking status (PR 1.16; 95% CI 1.06 to 1.26), body mass index (1.11; 1.02 to 1.21) and traditional cardiovascular risk factors (1.10; 1.01 to 1.19). Other markers of hypoxaemia tended to be associated with a higher prevalence of CAC >0. For CAC >400, a higher prevalence was observed with both a higher arousal index and less slow-wave sleep. Overall, associations were somewhat stronger among younger participants, but did not vary by sex or race/ethnicity. CONCLUSIONS: In this population-based multi-ethnic sample, severe OSA was associated with subclinical coronary artery disease (CAC >0), independent of obesity and traditional cardiovascular risk factors. Furthermore, the associations of the arousal index and slow-wave sleep with high CAC burden suggest that higher nightly sympathetic nervous system activation is also a risk factor. These findings highlight the potential importance of measuring disturbances in OSA as well as sleep fragmentation as possible risk factors for coronary artery disease. PMID- 26156529 TI - John T. Flynn, MD: Physician, Scholar, Educator, and Medical Editor. PMID- 26156530 TI - Pathogenesis and diagnostic criteria for rickets and osteomalacia - proposal by an expert panel supported by Ministry of Health, Labour and Welfare, Japan, The Japanese Society for Bone and Mineral Research and The Japan Endocrine Society. AB - Rickets and osteomalacia are diseases characterized by impaired mineralization of bone matrix. Recent investigations revealed that the causes for rickets and osteomalacia are quite variable. While these diseases can severely impair the quality of life of the affected patients, rickets and osteomalacia can be completely cured or at least respond to treatment when properly diagnosed and treated according to the specific causes. On the other hand, there are no standard criteria to diagnose rickets or osteomalacia nationally and internationally. Therefore, we summarize the definition and pathogenesis of rickets and osteomalacia, and propose the diagnostic criteria and a flowchart for the differential diagnosis of various causes for these diseases. We hope that these criteria and flowchart are clinically useful for the proper diagnosis and management of patients with these diseases. PMID- 26156531 TI - Confirmatory factor analysis of the Behavior Rating Inventory of Executive Functioning (BRIEF) in children and adolescents with ADHD. AB - The Behavior Rating Inventory of Executive Functioning (BRIEF) is a parent report measure designed to assess executive skills in everyday life. The present study employed a confirmatory factor analysis (CFA) to evaluate three alternative models of the factor structure of the BRIEF. Given the executive functioning difficulties that commonly co-occur with attention-deficit/hyperactivity disorder (ADHD), the participants included 181 children and adolescents with a diagnosis of ADHD. The results indicated that an oblique two-factor model, in which the Monitor subscale loaded on both factors (i.e., Behavioral Regulation, Metacognition) and measurement errors for the Monitor and Inhibit subscales were allowed to correlate, provided an acceptable goodness-of-fit to the data. This two-factor model is consistent with previous research indicating that the Monitor subscale reflects two dimensions (i.e., monitoring of task-related activities and monitoring of personal behavioral activities) and thus loads on multiple factors. These findings support the clinical relevance of the BRIEF in children with ADHD, as well as the multidimensional nature of executive functioning. PMID- 26156528 TI - Cross-sectional and longitudinal associations between objectively measured sedentary time and metabolic disease: the Coronary Artery Risk Development in Young Adults (CARDIA) study. AB - OBJECTIVE: Prolonged sedentary time (ST) might be contributing to the diabetes epidemic, but most studies have been cross-sectional and few have objectively measured ST. The purpose of this study was to evaluate cross-sectional and 5-year longitudinal relationships between ST and metabolic parameters and outcomes. RESEARCH DESIGN AND METHODS: This was an analysis of 2,027 Coronary Artery Risk Development in Young Adults (CARDIA) study participants (aged 38-50 years, 57% female, and mean BMI of 29.0 +/- 7.0 kg/m(2)) with accelerometry data (>=4 days with >=10 h/day) measured at the year 20 follow-up exam (2005-2006). Metabolic variables (fasting glucose, fasting insulin, 2-h postchallenge glucose, HOMA of insulin resistance [HOMA-IR], and HbA1c) and outcomes (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], prediabetes by HbA1c, and diabetes) were assessed concurrently and 5 years later. RESULTS: Average ST was 8.1 +/- 1.7 h/day or 55 +/- 10% of wear time. Each additional hour per day of ST was cross sectionally associated with a 3% higher fasting insulin and HOMA-IR (both P < 0.01) but not 5-year changes in metabolic parameters. Having >=10 h/day vs. <6 h/day of ST was associated with an odds ratio (OR) = 2.74 (95% CI 1.13, 6.62) for IGT and an OR = 3.80 (95% CI 1.39, 10.35) for diabetes. ST was not associated with prevalent IFG, prevalent prediabetes by HbA1c, or 5-year incidence of any metabolic outcomes (all P > 0.05). CONCLUSIONS: ST was independently related to insulin, HOMA-IR, and prevalent diabetes and IGT but did not predict 5-year changes in metabolic parameters or incidence of metabolic outcomes. These results suggest that higher ST may not be a risk factor for future metabolic outcomes, but more research with repeated ST measurement and longer follow-up is needed. PMID- 26156532 TI - The Effect of Bolus Consistency and Sex on Electrophysiological Measures of Hyolaryngeal Muscle Activity During Swallowing. AB - The purpose of this study was to investigate the effect of bolus consistency and sex on the activity of the submandibular hyolaryngeal muscles during swallowing. Twenty young, healthy adults (10 males, 10 females) swallowed four types of bolus material (thin liquid, thick liquid, pudding, and cookie) while being measured with surface electromyography. Measurements of peak contraction amplitude and contraction duration were computed from recorded electromyographic signals. Results from statistical analyses revealed a significant effect of bolus consistency on measures of peak contraction amplitude, but not contraction duration. There were no significant effects of sex on either measure. Findings from this study further the body of knowledge in electrophysiological measurements acquired during swallowing and their potential clinical application during assessment and treatment of dysphagia. PMID- 26156533 TI - Prostate cancer recurrence: can PSA guide imaging? PMID- 26156534 TI - Basal 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer. AB - AIM: To explore the relationship between basal (18) F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). METHODS: This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent (18) F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. RESULTS: The mean SUVmax +/- SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 +/- 5.57, 4.17 +/- 4.74 and 0.73 +/- 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax >= 6.05 or a nodal SUVmax >=2.25 were significantly correlated with DFS and OS. CONCLUSION: PET imaging with (18) F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. PMID- 26156535 TI - Bone kidney interactions. AB - The fact that bone disease and kidney disease co-exist is well known. Formally, this inter-relationship is called chronic kidney disease mineral bone disorder or CKD-MBD. Traditionally, it was thought that bone played a passive role in CKD-MBD - specifically that kidney disease caused disordered mineral metabolism which resulted in bone disease and ultimately fractures. More recently however our understanding of bone function in general and the role that bone plays in CKD-MBD in particular, has changed. This chapter will briefly review epidemiology of fractures in chronic kidney disease (CKD) and the roles that imaging and measuring markers of mineral metabolism can play in assessing fracture risk. We will then review more recent data consistent with the concept MBD occurs early in the course of CKD and, via the secretion of novel molecules and/or signalling pathways, the bone can influence other organ systems. PMID- 26156537 TI - Histopathology and immunophenotype of acrodermatitis chronica atrophicans correlated with ospA and ospC genotypes of Borrelia species. AB - BACKGROUND: Chronic cutaneous borreliosis (acrodermatitis chronica atrophicans, ACA) is a relatively rare manifestation of borreliosis attributed mainly to Borrelia afzelii. Chronic borreliosis has been associated with ospA and ospC genotypes. Literature on molecular investigations of Borrelia in lesions of ACA is scant. METHODS: Histopathological and immmunohistochemical features in 22 biopsies of ACA (16 patients) were examined. Paraffin-embedded biopsies were analyzed with polymerase chain reaction (PCR) assays targeting ospA and ospC genes, sequencing and phylogenetic analysis. RESULTS: Genotyping of ospA identified B. afzelii, serotype 2, in 12 of 16 patients. ospC-PCR was positive in seven patients revealing genotypes Af5 (n = 4), Af2 (n = 2) and Af6 (n = 1). Histopathologically, interstitial granulomatous infiltrates (CD68 positive) were common, combined with thickened collagen bundles and band-like infiltrates of CD4 positive T lymphocytes. Plasma cells were sparse/absent in 9 of 22 specimens even on staining with CD138. On CD34-staining, interstitial fibroblasts were often reduced akin to the situation in morphea. CONCLUSIONS: With assays targeting ospA and ospC genes we confirmed from paraffin-embedded biopsies that B. afzelii, serotype 2, osp C groups Af5, Af2 and Af6 is the main cause of ACA. Specimens commonly showed a combination of band-like T-cell-rich infiltrates with interstitial granulomatous features, a pattern previously under-recognized in ACA. This finding was particularly typical for lesions infected with ospC genotype Af5. PMID- 26156536 TI - Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells. AB - The formation of the immunological synapse between a T cell and the antigen presenting cell (APC) is critically dependent on actin dynamics, downstream of T cell receptor (TCR) and integrin (LFA-1) signalling. There is also accumulating evidence that mechanical forces, generated by actin polymerization and/or myosin contractility regulate T cell signalling. Because both receptor pathways are intertwined, their contributions towards the cytoskeletal organization remain elusive. Here, we identify the specific roles of TCR and LFA-1 by using a combination of micropatterning to spatially separate signalling systems and nanopillar arrays for high-precision analysis of cellular forces. We identify that Arp2/3 acts downstream of TCRs to nucleate dense actin foci but propagation of the network requires LFA-1 and the formin FHOD1. LFA-1 adhesion enhances actomyosin forces, which in turn modulate actin assembly downstream of the TCR. Together our data shows a mechanically cooperative system through which ligands presented by an APC modulate T cell activation. PMID- 26156538 TI - The Medical Use of Wheatgrass: Review of the Gap Between Basic and Clinical Applications. AB - A wide range of health benefits have been attributed to wheatgrass, the young grass of the common wheat plant Triticum aestivum. Its components include chlorophyll, flavonoids, and vitamins C and E. Forms of wheatgrass include fresh juice, frozen juice, tablets, and powders, with compositions varying according to their production processes, as well as to the growing conditions of the wheatgrass. Laboratory in vitro studies, mostly using the fermented wheat germ extract, have demonstrated anti-cancer potential and have identified apoptosis as a possible mechanism. In animal experiments, wheatgrass demonstrated benefits in cancer prevention and as an adjunct to cancer treatment, as well as benefits to immunological activity and oxidative stress. Clinical trials show that wheatgrass may induce synergistic benefits to chemotherapy and may attenuate chemotherapy related side effects, as well as benefit rheumatoid arthritis, ulcerative colitis, hematological diseases, diabetes, obesity, and oxidative stress. However, all the trials were small and a number of methodological problems arose. No adverse events of wheatgrass have been reported, although some forms pose problems of tolerability. The popularity of wheatgrass continues to grow. Nevertheless, the advantages seen in the clinical trials need to be proved in larger studies before clinical recommendations for the public can be given. PMID- 26156539 TI - Main Anti-tumor Angiogenesis Agents Isolated From Chinese Herbal Medicines. AB - With a long history of clinical use, Chinese herbal medicine (CHM) is emerging as a noticeable choice for its multi-level, multi-target and coordinated intervention effects against tumor. Recently, many agents from CHM have shown powerful anti-angiogenic activities against tumor. In this review, we discussed the anti-tumor angiogenic activities of 6 kinds of agents from CHM (sulfated polysaccharides/glycopeptides, flavonoids, artemisinin, arsenic trioxide, ginsenoside, and tanshinone). The underlying pharmacological mechanisms of cancer angiogenesis inhibition by these agents are also gradually shown to us. Sulfated polysaccharides/glycopeptides and flavonoids may have synergistic effects with targeted anti-angiogenic drugs mainly targeting VEGF pathway by inhibiting bFGF and HIF-1alpha pathway, respectively. It is interesting that artemisinin and arsenic trioxide, two famous natural products worldwide, also have antitumor activity at least in part via angiogenesis inhibition. In addition, some natural products that are widely used for patients with cancer, such as ginseng and danshen, act as double-edged swords for tumor angiogenesis. Our review is aimed at providing an understanding of anti-angiogenic compounds from CHM and we propose that these breakthrough findings may have important implications for targeted-angiogenesis therapy and modernization of CHM. PMID- 26156540 TI - Vitamin A and Diabesity: New Insight for Drug Discovery. AB - Obesity, insulin resistance, metabolic syndrome and type 2 diabetes have reached epidemic proportions, from the term: diabesity. Vitamin A is delivered by a specific binding protein called retinol-binding protein 4 (RBP4) a soluble protein, emerging to have a role in insulin resistance, the major cause of diabetes is highly associated with adipose tissue inflammation and obesity with action. RBP4, interacts with two receptors, the Toll-like receptor 4 (TLR4) and the plasma membrane protein are stimulated by retinoic acid 6 (STRA6), leading to the activation of c-Jun N-terminal protein kinase (JNK) pathways and JAK2/STAT5 cascade, respectively. Both mechanisms sustain insulin resistance. Therefore, ablation of STRA6 protects mice from RBP4-induced suppression of insulin signaling. In addition, mice harboring deletion of a specific chaperon for retinol, show infiltration of alpha-cells in the core of pancreatic islets, where usually only beta-cells reside, showing a pre-diabetic like phenotype. Not only proteins in vitamin A shuttle and signaling are emerging in diabesity, recently, the discovery of 9cis retinoic acid (9cRA) with effects on controlling glucose levels have opened a new scenario. So far, only pancreas beta-cells have been shown to synthesize it, and high levels of 9cRA correlate with obesity mice models. In this article, we summarize the recent literature present on this topic raising the hypothesis. PMID- 26156541 TI - Engineered Polymer-Based Nanomaterials for Diagnostic, Therapeutic and Theranostic Applications. AB - Nanomedicine can be defined as the medical application of molecular nanotechnology and it plays a key role and pharmaceutical research and development, especially related to cancer prevention, monitoring, diagnosis and treatment. In this context, nanomaterials are attracting significant research interest due to their abilities to stay in the blood for long time, accumulate in pathological sites including tumors or inflammatory areas via the enhanced permeability and retention (EPR) effect, and facilitate targeted delivery of specific therapeutic agents. In the last decades, considerable attention was attracted by the development of nano-sized carriers, based on natural or synthetic polymers, able to provide the controlled release of anticancer drugs in the aim to overcome the drawbacks associated to the conventional chemotherapy. Furthermore, when loaded with imaging agents, this kind of systems offers the opportunity to exploit optical or magnetic resonance imaging (MRI) in cancer diagnosis. Polymeric materials are characterized by several functionalities where both therapeutic and imaging components, and also targeting moieties, can be attached for simultaneous targeted therapy and imaging providing innovative platforms defined as theranostic agents with a great potential in monitoring and treatment of cancer. PMID- 26156542 TI - Stability-Indicating Methods for NSAIDs in Topical Formulations and Photoprotection in Host-Guest Matrices. AB - Photostability tests applied on topical commercial formulations containing non steroidal anti-inflammatory drugs have demonstrated a clear degradation of the active compounds when exposed to light. The photodegradation profile of these drugs is usually monitored by spectrophotometric or chromatographic techniques according to the international ICH rules for photostability testing. In the last years, the data are processed ever more by multivariate analysis, as principal component analysis, partial least squares, multivariate curve resolution. These techniques have proved to be able to resolve the complex data sets from evolving chemical processes, by estimating the number of the involved components, their pure spectra and concentration profiles. When applied to the study of drug photodegradation, the multivariate approach has been able to define completely the reaction mechanisms and kinetics parameters. Several novel pharmaceutical formulations have been described to improve the photostability of NSAIDs in topical formulations. The common use of light protective packaging has recently been replaced or supplemented by incorporating suitable excipients in the drug formulations. The addition of UV absorbent agents, deactivating quench reactions that are either singlet oxygen-driven or involve free radicals, has had good success. A clear improvement in the light protection has been shown by entrapping the drugs into supramolecular matrices as cyclodextrins, liposomes, niosomes and other host-guest matrices. The present review gives an updated overview on the stability-indicating methods adopted for a series of NSAIDs in topical formulations and the supramolecular matrices designed to minimize the drug photodegradation. PMID- 26156543 TI - Carbazole derivatives: a promising scenario for breast cancer treatment. AB - Chemotherapeutics used in cancer treatment may elicit pleiotropic effects interfering, for instance, directly on DNA metabolism or on endoplasmic organelles functions. Recently there has been a trend towards the use of molecular-targeted therapies as alternative treatments of cancer, arising from the need to overcome the onset of undesired side effects or drug-resistance. Thus, a major challenge is the design and synthesis of new agents able to interact with specific cellular components, often over-expressed or altered in cancerous cells, such as telomerase and topoisomerase or protein kinases, with reduced toxicity at effective doses. The main molecular targets for the development of new anticancer drugs include: cell surface receptors, signal transduction pathways, enzymes, gene transcription, ubiquitin-proteasome/heat shock proteins, and anti-angiogenic agents. Several natural or synthetic polycyclic molecules with carbazolic nucleus, which show attractive drug-like properties, were identified with the aim to increase their biological activities and their specificity, obtaining cytotoxic agents effective in a panel of cancer cell lines. The cytotoxic profile of these compounds has been assessed using several in vitro assays as, for instance, MTT, colony formation, and flow cytometry assays and some of these compounds showed an interesting profile at sub micromolar concentrations. The usefulness of some carbazole derivatives has been demonstrated, as well, in preclinical studies. PMID- 26156544 TI - Natural Products as Promising Antitumoral Agents in Breast Cancer: Mechanisms of Action and Molecular Targets. AB - Extensive research over the past several decades has identified numerous dietary and phytochemical compounds that have chemopreventive potential and could represent an important source of anti-cancer lead molecules. In this scenario several nutritional factors have attracted considerable attention as modifiable risk factor in the prevention of breast cancer, the most frequently diagnosed cancer and a major cause of death among women worldwide. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for breast cancers able also to counteract the recurrent phenomenon of resistance to hormonal and targeted therapy that represent the first-line treatment in the management of breast cancer patients. The present review focuses on chemopreventive and anti-cancer activities of different bioactive compounds obtained from dietary sources such as Omega-3 fatty acids, naturally present in fish, Resveratrol (3,5,40-trihydroxy-transstilbene), a phytoalexin found in grapes and Epigallocatechin Gallate, a polyphenolic compound found in green tea, or purified from medicinal plant (Oldenlandia Diffusa) and fruits (Ziziphus Jujube) highlighting their potential use in breast cancer treatment. Herein, we discuss the molecular mechanisms by which the bioactive compounds can inhibit carcinogenesis by regulating antioxidant enzyme activities, and inducing antiproliferative and apoptotic effects in different breast cancer cell lines. Understanding the mechanism of action of dietary compounds or traditionally used herbs having potential preventive and therapeutic effects on cancer may provide a rationale for further translational studies. This review emphasizes the importance, in the next future, of a proper scientific validation of these natural bioactive compounds for clinical use in the therapeutic portfolio for breast cancer. PMID- 26156545 TI - Bergamot (Citrus bergamia Risso) Flavonoids and Their Potential Benefits in Human Hyperlipidemia and Atherosclerosis: an Overview. AB - Elevated serum cholesterol, triglycerides and LDL levels are often associated with an increased incidence of atherosclerosis and coronary artery disease. The most effective therapeutic strategy against these diseases is based on statins administration, nevertheless some patients, especially those with metabolic syndrome fail to achieve their recommended LDL targets with statin therapy, moreover, it may induce many serious side effects. Several scientific studies have highlighted a strong correlation between diets rich in flavonoids and cardiovascular risk reduction. In particular, Citrus bergamia Risso, also known as bergamot, has shown a significant degree of hypocholesterolemic and antioxidant/radical scavenging activities. In addition, this fruit has attracted considerable attention due to its peculiar flavonoid composition, since it contains some flavanones that can act as natural statins. Hence, the study of bergamot flavonoids as metabolic regulators offers a great opportunity for screening and discovery of new therapeutic agents. Cholesterol metabolism, flavonoid composition and potential therapeutic use of C. bergamia Risso will be discussed in the following review. PMID- 26156546 TI - New Potential Pharmaceutical Applications of Hypericum Species. AB - The genus Hypericum includes more than 450 species distributed in Europe, North America, North Africa and West Asia. These plants are widely used in folk medicine for the treatment of inflammation, bacterial and viral infections, burns and gastric disorders. The use for alleviating inflammation and promoting wound healing is well known for H. Perforatum L. (St. John's wort) and other species. Because of its pharmacological activity, H. perforatum L. is one of the most important species of this genus. This plant has been largely utilized for its efficacy in the treatment of mild to moderate depression. However, some other species have been utilized in traditional medicine and have been studied for their phytochemical composition and for their biological activities to date. Hypericum species contain biologically active secondary metabolites belonging to at least ten different classes, with prevalence of naphthodianthrones (hypericin and pseudohypericin), phloroglucinols (hyperforin), flavonoids (rutin, hyperoside, isoquercitrin, quercitrin, quercetin, amentoflavone) and phenylpropanoids (chlorogenic acid). However, great variations in contents have been reported for wild populations worldwide. The purpose of this review is to provide an overview of most recent studies about potential pharmaceutical applications of plants belonging to Hypericum genus. The most interesting isolated active principles and both in vitro and in vivo effects of Hypericum extracts are presented and discussed. PMID- 26156547 TI - Nanotechnology for the Environment and Medicine. AB - Nanotechnology encompasses the production and applications of physical, chemical, and biological systems at scales ranging from individual atoms or molecules to around 100 nanometres, as well as the integration of the resulting nanostructures into larger systems. Nanomaterials differ from bulk materials for their relatively larger surface-area-to-mass ratio, consequently they become more chemically reactive and can show different optical, magnetic and electrical behaviours. In recent years, engineered nanomaterials have gained a particular attention in some fields such as environmental protection (soil, air and water remediation/treatment) and medicine (bio-sensing, imaging, and drug delivery). Nanoparticles can be used to monitor in real-time some pollutants (including heavy metal ions, organic compounds, microbiological pathogens, etc.) present even at extremely low concentrations in different environments. The use of nanomaterials for waste remediation/treatment results in a technology more cost effective and rapid than current conventional approaches thanks to their enhanced surface area, transport properties, and sequestration characteristics. In addition, the integration of molecular biology and medicine with nanotechnology has resulted in new active nanostructures able to interact with biological systems. Nanocarriers based on carbon nanotubes, fumed silica (SiO2), titanium dioxide (TiO2), and magnetite and maghemite (Fe3O4, and gamma-Fe2O3) nanoparticles have a distinct advantage over other drug carriers as they can be opportunely designed to reach the desired targets. As a consequence, such nanostructures can represent an important platform for enhanced medical imaging and controlled drug delivery. Here, some applications of nanomaterials as water purifying agents and drug delivery systems are reported. PMID- 26156548 TI - Recent Knowledge on Medicinal Plants as Source of Cholinesterase Inhibitors for the Treatment of Dementia. AB - Dementia is becoming a major public health problem worldwide. The most common form of dementia is Alzheimer's disease (AD), characterized by a deficient cholinergic transmission, deposition of amyloid plaques and neurofibrillary tangles, and neuro-inflammation that result in progressive degeneration and/or death of nerve cells and cognitive impairment. At present, AD cannot be prevented or cured, so the symptomatic relief obtainable by the use of acetylcholinesterase (AChE) inhibitors is one of the therapeutic strategies. Accumulated evidence suggests that naturally occurring compounds may potentially improve memory and cognitive function, and prevent neurodegeneration. Even today the search for new neuroprotective agents of natural origin is very active. The neuroprotective effects of medicinal plants covering studies of the last years will be summarized and discussed in this review choosing a family classification with particular emphasis on extracts and isolated compounds as promising new drugs. The search of a multifunctional potential anti-AD agent able to act on different crucial targets, such as galanthamine, quercetin and timosaponin AIII, could be a useful approach to recognizing therapeutics against AD. PMID- 26156549 TI - Carbon Nanohybrids as Electro-Responsive Drug Delivery Systems. AB - Electro-responsive nanomaterials are usually made with polyelectrolytes able to undergo shrinkage or swelling by tuning on electrical fields. Nevertheless, the electrical conductivity of many polymeric materials used for the fabrication of release devices is not high enough to achieve an effective modulation of the drug release. The incorporation of conducting materials (e.g. carbon nanostructures) in polymeric networks has been proposed as a valuable strategy to overcome this limitation. In this regard, carbon nanotubes and graphene, by virtue of their unique chemical structures and attractive physiochemical properties, have been receiving exciting attention primarily in biology and medicine. By their incorporation into composite hydrogels, the biocompatibility and biodegradability of polymers can be merged with the favorable properties of carbon nanostructures, such as enhanced cellular uptake, electromagnetic, and magnetic behavior. The applicability of carbon hybrid materials to modulate release of therapeutics in response to an external current voltage, is being extensively investigated in the present review. PMID- 26156550 TI - BIOCOMPATIBLE TARGETING HYDROGELS FOR BREAST CANCER TREATMENT. AB - Hydrogels have received growing attention as materials for drug delivery systems (DDS) because of their biodegradable and biocompatible properties. DDS were developed to optimize the therapeutic properties of drug products and to render them more safe, effective, and reliable. In the past, drugs were frequently administered orally, as liquids or in powder forms. To avoid problems incurred through the utilization of the oral route of administration, new dosage forms, DDS, containing the drugs were introduced. They can deliver drugs directly to the intended site of action and can also improve treatment efficacy, while minimizing unwanted side effects elsewhere in the body, which often limit the long-term use of many drugs, and provide better efficacy of treatment. Biocompatible hydrogels are an example of such systems available for therapeutic use. In this review, results from recent publications concerning these systems are discussed. Hydrogels show superior effectiveness over conventional methods of treatment providing controlled release of active substances. They are of interest in medical applications such as breast cancer treatment. PMID- 26156551 TI - Bioassay-guided isolation and POM analyses of a new immunomodulatory polyphenolic constituent from Callistemon viridiflorus. AB - Chromatographic separation of 80% EtOH extract of Callistemon viridiflorus leaves led to the isolation of six known constituents (1-6) along with a new polyphenolic compound 7 identified as apigenin 4'-O-beta-d-glucopyranosyl-(1"' -> 4")-O-beta-d-glucopyranoside. The ethanolic extract of C. viridiflorus leaves and isolated compounds were evaluated for in vitro immunomodulatory activity by means of RAW 264.7 macrophages proliferation (MTT) assay. Ethanolic extract of leaves and compounds 1, 3, 4, 6 and 7 caused a significant increase in macrophage proliferation; these findings may suggest that this medicinal plant could be utilised as an excellent source of compounds for immunomodulatory activity. PMID- 26156552 TI - An Efficient Strategy Developed for Next-Generation Sequencing of Endosymbiont Genomes Performed Using Crude DNA Isolated from Host Tissues: A Case Study of Blattabacterium cuenoti Inhabiting the Fat Bodies of Cockroaches. AB - Whole-genome sequencing has emerged as one of the most effective means to elucidate the biological roles and molecular features of obligate intracellular symbionts (endosymbionts). However, the de novo assembly of an endosymbiont genome remains a challenge when host and/or mitochondrial DNA sequences are present in a dataset and hinder the assembly of the genome. By focusing on the traits of genome evolution in endosymbionts, we herein developed and investigated a genome-assembly strategy that consisted of two consecutive procedures: the selection of endosymbiont contigs from an output obtained from a de novo assembly performed using a TBLASTX search against a reference genome, named TBLASTX Contig Selection and Filtering (TCSF), and the iterative reassembling of the genome from reads mapped on the selected contigs, named Iterative Mapping and ReAssembling (IMRA), to merge the contigs. In order to validate this approach, we sequenced two strains of the cockroach endosymbiont Blattabacterium cuenoti and applied this strategy to the datasets. TCSF was determined to be highly accurate and sensitive in contig selection even when the genome of a distantly related free living bacterium was used as a reference genome. Furthermore, the use of IMRA markedly improved sequence assemblies: the genomic sequence of an endosymbiont was almost completed from a dataset containing only 3% of the sequences of the endosymbiont's genome. The efficiency of our strategy may facilitate further studies on endosymbionts. PMID- 26156553 TI - Phylogenetic Diversity of aprA Genes in Subseafloor Sediments on the Northwestern Pacific Margin off Japan. AB - Markedly diverse sequences of the adenosine-5'-phosphosulfate reductase alpha subunit gene (aprA), which encodes a key enzyme in microbial sulfate reduction and sulfur oxidation, were detected in subseafloor sediments on the northwestern Pacific off Japan. The aprA gene sequences were grouped into 135 operational taxonomic units (90% sequence identity), including genes related to putative sulfur-oxidizing bacteria predominantly detected in sulfate-depleted deep sediments. Our results suggest that microbial ecosystems in the subseafloor biosphere have phylogenetically diverse genetic potentials to mediate cryptic sulfur cycles in sediments, even where sulfate is rarely present. PMID- 26156554 TI - Nitrosomonas stercoris sp. nov., a Chemoautotrophic Ammonia-Oxidizing Bacterium Tolerant of High Ammonium Isolated from Composted Cattle Manure. AB - Among ammonia-oxidizing bacteria, Nitrosomonas eutropha-like microbes are distributed in strongly eutrophic environments such as wastewater treatment plants and animal manure. In the present study, we isolated an ammonia-oxidizing bacterium tolerant of high ammonium levels, designated strain KYUHI-S(T), from composted cattle manure. Unlike the other known Nitrosomonas species, this isolate grew at 1,000 mM ammonium. Phylogenetic analyses based on 16S rRNA and amoA genes indicated that the isolate belonged to the genus Nitrosomonas and formed a unique cluster with the uncultured ammonia oxidizers found in wastewater systems and animal manure composts, suggesting that these ammonia oxidizers contributed to removing higher concentrations of ammonia in strongly eutrophic environments. Based on the physiological and phylogenetic data presented here, we propose and call for the validation of the provisional taxonomic assignment Nitrosomonas stercoris, with strain KYUHI-S as the type strain (type strain KYUHI S(T) = NBRC 110753(T) = ATCC BAA-2718(T)). PMID- 26156555 TI - Peritraumatic Distress and Dissociation in Prolonged Grief and Posttraumatic Stress Following Violent and Unexpected Deaths. AB - This study examined associations between the violence of a loss and the suddenness of a loss and symptom levels of prolonged grief disorder (PGD) and posttraumatic stress disorder (PTSD) after the death of a loved one. A further aim was to investigate whether peritraumatic distress (i.e., fear, helplessness, and horror) and peritraumatic dissociation mediate the emotional impact of violent losses and unexpected losses. We obtained self-reported data from 265 individuals bereaved in the previous 3 years by losses due to violent causes (17%) or illness (83%). Outcomes showed that participants who experienced violent losses (due to homicide, suicide, or accident) reported more PGD symptoms and PTSD symptoms compared to those confronted with illness loss. In this latter group, greater perceived unexpectedness was positively associated with PGD severity and PTSD severity. Multiple mediation analyses showed that the impact of violent loss and unexpectedness of the loss on PGD severity and PTSD severity was fully mediated by peritraumatic distress and dissociation; peritraumatic helplessness and peritraumatic dissociation (but not peritraumatic fear and horror) emerged as unique mediators. Findings suggest that both violent and unexpected losses exacerbate postloss psychopathology, which is at least partially because of such losses yielding more intense acute helplessness and dissociative responses. PMID- 26156557 TI - Suspected adverse reactions to contrast media in Campania Region (Italy): results from 14 years of post-marketing surveillance. AB - OBJECTIVE: During the last years in Italy, contrast media (CM) use increased. An increase of monitoring activities on CM-induced adverse drug reaction (ADR) is necessary, also in our regional territory. The main aim of this study was to give a preliminary evaluation of all Spontaneous Reports of ADRs (SRA) attributed to CM sent to Campania Pharmacovigilance Regional Center (CRFVC) from 01 January 2001 to 31 October 2014. RESEARCH DESIGN AND METHODS: For each SRA we evaluated: frequency and source, ADRs onset (time to event, seriousness and outcome), socio demographic characteristics and risk factors of cases, the most reported CM (checking for pharmacodynamic and pharmacokinetic interactions). RESULTS: A total of 111 SRA were sent to CRFVC; specialist in radiology was the main source of reports. Ninety-seven SRA (87.3%) were referable to hypersensitivity reactions. Thirty-four SRA (30.6%) reported serious ADRs. The most reported CM were iopamidol, gadobenic acid and gadoteric acid. We identified two SRA induced by pharmacokinetic and/or pharmacodynamic interactions. CONCLUSIONS: During 14 years of post-marketing surveillance, only few SRA concerning CM-induced ADRs were sent to CRFVC probably due to underreporting. We aim to improve monitoring activity on CM-induced ADRs especially in hospitals. Most reported ADR and CM were in line with current body of literature. PMID- 26156556 TI - The extended AT-hook is a novel RNA binding motif. AB - The AT-hook has been defined as a DNA binding peptide motif that contains a glycine-arginine-proline (G-R-P) tripeptide core flanked by basic amino acids. Recent reports documented variations in the sequence of AT-hooks and revealed RNA binding activity of some canonical AT-hooks, suggesting a higher structural and functional variability of this protein domain than previously anticipated. Here we describe the discovery and characterization of the extended AT-hook peptide motif (eAT-hook), in which basic amino acids appear symmetrical mainly at a distance of 12-15 amino acids from the G-R-P core. We identified 80 human and 60 mouse eAT-hook proteins and biochemically characterized the eAT-hooks of Tip5/BAZ2A, PTOV1 and GPBP1. Microscale thermophoresis and electrophoretic mobility shift assays reveal the nucleic acid binding features of this peptide motif, and show that eAT-hooks bind RNA with one order of magnitude higher affinity than DNA. In addition, cellular localization studies suggest a role for the N-terminal eAT-hook of PTOV1 in nucleocytoplasmic shuttling. In summary, our findings classify the eAT-hook as a novel nucleic acid binding motif, which potentially mediates various RNA-dependent cellular processes. PMID- 26156558 TI - Impact of KIBRA Polymorphism on Memory Function and the Hippocampus in Older Adults. AB - The single nucleotide polymorphism rs17070145 within the KIBRA gene (kidney and brain expressed protein) has been associated with variations in memory functions and related brain areas. However, previous studies yielded conflicting results, which might be due to divergent sample characteristics or task-specific effects. Therefore, we aimed to determine the impact of KIBRA genotype on learning and memory formation, and volume, microstructural integrity and functional connectivity (FC) of the hippocampus and its subfields in a well-characterized cohort of healthy older adults. One-hundred and forty subjects (72 women, age 50 80) were KIBRA genotyped and memory was tested using the Auditory Verbal Learning Task. Also, subjects underwent structural and resting-state functional magnetic resonance imaging at 3T. Subfields were delineated using automated segmentation (FreeSurfer software). Microstructural integrity was measured using mean diffusivity (MD) derived from diffusion tensor images. Seed-based analyses were used to assess FC patterns of the hippocampus. KIBRA T-allele carriers showed a trend for better memory performance, and in the hippocampus significantly higher volumes and partly lower MD, indicative for better microstructure, compared with non-T-allele carriers in the cornu ammonis (CA)2/3 and CA4/dentate gyrus subfields (all P?0.008, Bonferroni corrected). Also, T-allele carriers exhibited lower FC of the left hippocampus with areas outside the synchronized HC network. In sum, we could show for the first time that older T-allele carriers exhibited larger volumes and better microstructure within those hippocampus subfields that are implicated in long-term potentiation and neurogenesis, key features of memory processes. Moreover, T-allele carriers showed a more selective FC network of the hippocampus. PMID- 26156559 TI - Estradiol and Progesterone have Opposing Roles in the Regulation of Fear Extinction in Female Rats. AB - Fear extinction, the laboratory basis of exposure therapy for anxiety disorders, fluctuates across the female rat estrous cycle, where extinction is enhanced during proestrus (high estradiol and progesterone), and impaired during metestrus (low estradiol and progesterone). During the estrous cycle increasing levels of estradiol precede and then overlap with increased levels of progesterone. We sought to isolate the impact of these hormonal changes on fear extinction by systematically treating ovariectomized female rats with estradiol alone, or in combination with progesterone. We found that estradiol alone facilitated extinction recall, whereas the effects of progesterone on estradiol-treated rats were biphasic and dependent on the time interval between progesterone administration and extinction training. Progesterone potentiated estradiol's facilitation of extinction recall when extinction training occurred 6 h after progesterone administration. However, progesterone abolished estradiol's facilitation of extinction recall when extinction training occurred 24 h after progesterone administration. Furthermore, in naturally cycling rats, blocking progesterone receptor activation during proestrus (when progesterone levels peak) prevented the impairment in extinction recall in rats extinguished during metestrus. These results suggest that in naturally cycling females whereas cyclical increases in estradiol facilitate fear extinction, cyclical increases in progesterone may lead to fear extinction impairments. As extinction training took place after the hormonal treatments had been metabolized, we propose that genomic mechanisms may at least partly mediate the impact of cyclic fluctuations in sex hormones on fear extinction. PMID- 26156560 TI - Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial. AB - OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA. MATERIALS AND METHODS: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention. RESULTS: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05). CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls. PMID- 26156561 TI - Molecular characterization influencing metal resistance in the Cupriavidus/Ralstonia genomes. AB - Our environment is stressed with a load of heavy and toxic metals. Microbes, abundant in our environment, are found to adapt well to this metal-stressed condition. A comparative study among five Cupriavidus/Ralstonia genomes can offer a better perception of their evolutionary mechanisms to adapt to these conditions. We have studied codon usage among 1051 genes common to all these organisms and identified 15 optimal codons frequently used in highly expressed genes present within 1051 genes. We found the core genes of Cupriavidus metallidurans CH34 have a different optimal codon choice for arginine, glycine and alanine in comparison with the other four bacteria. We also found that the synonymous codon usage bias within these 1051 core genes is highly correlated with their gene expression. This supports that translational selection drives synonymous codon usage in the core genes of these genomes. Synonymous codon usage is highly conserved in the core genes of these five genomes. The only exception among them is C. metallidurans CH34. This genomewide shift in synonymous codon choice in C. metallidurans CH34 may have taken place due to the insertion of new genes in its genomes facilitating them to survive in heavy metal containing environment and the co-evolution of the other genes in its genome to achieve a balance in gene expression. Structural studies indicated the presence of a longer N-terminal region containing a copper-binding domain in the cupC proteins of C. metallidurans CH3 that helps it to attain higher binding efficacy with copper in comparison with its orthologs. PMID- 26156562 TI - Functional urology 2015. PMID- 26156563 TI - DNA-dependent targeting of cell nuclei by a lupus autoantibody. AB - A nuclear-penetrating lupus anti-DNA autoantibody, 3E10, has been found to inhibit DNA repair and selectively kill certain cancer cells that are highly vulnerable to DNA damage. In addition, a 3E10 single chain variable fragment (scFv) has been developed for use as a delivery vehicle to carry therapeutic cargo proteins into cell nuclei. A greater understanding of the mechanism by which 3E10 penetrates cell nuclei is needed to help determine the scope of its potential therapeutic applications. Here we show that the presence of extracellular DNA significantly enhances the nuclear uptake of 3E10 scFv. In addition, we find that 3E10 scFv preferentially localizes into tumor cell nuclei in vivo, likely due to increased DNA in the local environment released from ischemic and necrotic regions of tumor. These data provide insight into the mechanism of nuclear penetration by 3E10 and demonstrate the potential for use of 3E10 in therapeutic approaches to diseases ranging from malignancy to ischemic conditions such as stroke. PMID- 26156564 TI - Aflibercept in wet AMD beyond the first year of treatment: recommendations by an expert roundtable panel. AB - This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a 'treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for >=3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the re-treatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease. PMID- 26156565 TI - Rosette-forming glioneuronal tumor originating in the hypothalamus. AB - Rosette-forming glioneuronal tumors (RGNT) of the fourth ventricle are slow growing tumors that primarily involve the fourth ventricular region. We here report the first patient, an 8-year-old girl, with an RGNT originating in the hypothalamus and manifesting with precocious puberty. After partial removal, the remaining tumor showed rapid enlargement, and the pathologic diagnosis at the second surgery revealed histopathologic features similar to those found in the initial samples, including biphasic patterns of neurocytic rosettes and GFAP stained astrocytic components. These tumor cells had mildly atypical nuclei; however, mitotic figures and necrosis were absent. Eosinophilic granular bodies and a glomeruloid vasculature were found, but Rosenthal fibers were absent. The Ki-67 proliferative index was 3.5 % (vs 1.1 % at the initial surgery). No recurrence was recorded during the 3-year period after the proton radiotherapy. PMID- 26156566 TI - Demographic comparison of sweetpotato weevil reared on a major host, Ipomoea batatas, and an alternative host, I. triloba. AB - In this study, we collected life table data for the sweetpotato weevil, Cylas formicarius, grown on Ipomoea batatas and Ipomoea triloba, and analyzed them using an age-stage, two-sex life table. We also demonstrated the growth potential of C. formicarius on these two host plants by using population projection. These data will be useful to the growers to the selection or eradication of host plants in an integrated control strategy for C. formicarius for the entire area of the targeted areas. We found that C. formicarius developed faster on I. batatas than on I. triloba. The developmental times of the larval and pupal stages on I. batatas than on I. triloba were 37.01 and 8.3 days. The adult females emerged before and began to produce eggs at 42 days earlier when reared on I. batatas. The fecundity of females was 90.0 eggs on I. batatas significantly higher than the mean fecundity of 68.5 eggs on I. triloba. Although this insect has a higher intrinsic rate of increase on I. batatas, the study indicated that C. formicarius can successfully survive and reproduce on both host plants. PMID- 26156567 TI - Retinal pigment epithelial detachment associated with retinal pigment epithelium thinning revealed by optical coherence tomography. AB - PURPOSE: To clarify the characteristics and outcomes of unusual retinal pigment epithelial detachments (PEDs). These PEDs had one or several sites of apparent thinning of the RPE, or no RPE at all, as shown on optical coherence tomography (OCT). METHODS: Eight cases with PEDs showed apparent thinning of the RPE in the roof of the PED at one or more sites on OCT. Color fundus photographs, fundus examination records, fluorescein angiograms (FAs) and/or indocyanine green angiograms (ICGAs), obtained with simultaneous OCT using Spectralis((r)), and fundus autofluorescence were evaluated. Macular findings, prior to baseline PED detection, were investigated in three cases. Follow-up results were also reviewed in three cases. RESULTS: Well-delineated grayish-white lesions at the level of the choroid observed through a hypo- or unpigmented area corresponding to the area of thinning in the RPE on OCT. These lesions showed intense hyperfluorescence due to staining on both FAs and ICGAs as well as hypofluorescence on fundus autofluorescence. In three eyes, smaller PEDs had been observed at the same locations and were thus taken as the baseline PEDs on images obtained 22-94 months before this study. In two of the three eyes followed up for at least 35 months from baseline, the PEDs collapsed, leaving RPE choriocapillaris atrophy in one eye and RPE tear in the other. CONCLUSION: Lesions corresponding to the area of thinning in the RPE on OCT may indicate hypo or unpigmented RPE, possibly as a result of focal damage due to longstanding PEDs. These PEDs may lead to unexpected complications during long-term follow-up. PMID- 26156568 TI - The Differential Effects of Social Media Sites for Promoting Cancer Risk Reduction. AB - Social media are potentially valuable tools for disseminating cancer education messages, but the differential effects of various sites on persuasive outcomes are unknown. In an effort to inform future health promotion, this research tested the effects of Facebook, YouTube, Twitter, and blogs for delivering a cancer risk reduction message. Using an experimental design, participants were randomly placed in several conditions that delivered the same message but with different forms of social media. Effects on comprehension and attitudes were examined, as they are important variables in the behavior change process. YouTube led to higher comprehension and stronger attitudes toward cancer risk reduction than Twitter, but there were no differences between other sites. Additionally, YouTube led to stronger attitudes toward cancer risk reduction as compared to Facebook, but not any other sites. These results demonstrate that, even if the message is kept constant, the form of social media used to deliver content can have an effect on persuasive outcomes. More research is needed to determine the mechanisms behind the differences found, however. Altogether, this line of research is valuable for any individuals seeking to use social media for health promotion purposes and could have direct implications for the development of cancer risk reduction campaigns. PMID- 26156569 TI - Efficient routes towards a series of 5,5'-bithiazolidinylidenes as pi-electron acceptors. AB - Different approaches have been studied in order to prepare efficiently the sulfur rich electron acceptor, DEBTTT. Among the various routes used, the one going through the synthesis of a bicyclic derivative, where the thiazole-2-chalcogenone is fused with a 1,3-dithiole-2-one, leads to the target molecule under milder conditions and better yield. Thus, this approach has been explored for the synthesis of a series of acceptors either by modifying the substituent on the thiazole core or by changing the exocyclic chalcogen atoms. All these sulfur rich electron acceptors exhibit short intra- and intermolecular SS contacts in the solid state. Electrochemical investigations show that the nature of the exocyclic chalcogen atom of the thiazole ring has a significant influence on the accepting ability as a cathodic shift of about 220 mV is observed just by changing sulfur for oxygen. This structural modification enables the tuning of the redox properties. PMID- 26156571 TI - Magnetic susceptibility as a direct measure of oxidation state in LiFePO4 batteries and cyclic water gas shift reactors. AB - The possibility of correlating the magnetic susceptibility to the oxidation state of the porous active mass in a chemical or electrochemical reactor was analyzed. The magnetic permeability was calculated using a hierarchical model of the reactor. This model was applied to two practical examples: LiFePO4 batteries, in which the oxidation state corresponds with the state-of-charge, and cyclic water gas shift reactors, in which the oxidation state corresponds to the depletion of the catalyst. In LiFePO4 batteries phase separation of the lithiated and delithiated phases in the LiFePO4 particles in the positive electrode gives rise to a hysteresis effect, i.e. the magnetic permeability depends on the history of the electrode. During fast charge or discharge, non-uniform lithium distributionin the electrode decreases the hysteresis effect. However, the overall sensitivity of the magnetic response to the state-of-charge lies in the range of 0.03%, which makes practical measurement challenging. In cyclic water gas shift reactors, the sensitivity is 4 orders of magnitude higher and without phase separation, no hysteresis occurs. This shows that the method is suitable for such reactors, in which large changes of the magnetic permeability of the active material occurs. PMID- 26156570 TI - Emerging challenges in managing hepatitis B in HIV patients. AB - Roughly 10 % of HIV-positive individuals worldwide have concomitant chronic hepatitis B virus (HBV) infection, with large differences between geographical regions and/or risk groups. Hepatitis B is a preventable infection with vaccines. However, it cannot be eradicated once acquired, resembling HIV and in contrast with HCV. In developed countries, hepatitis B exhibits particular features in the HIV population. First, HBV infection is less frequently misdiagnosed than in the general population. Second, nucleos(t)ide analogs active against HBV are widely used as part of antiretroviral combinations and are taken by most HIV patients. Lastly, as the HIV population ages given the success of antiretroviral therapy, non-AIDS co-morbidities are becoming a major cause of disease, for which specific drugs are required, increasing the risk of interactions and hepatotoxicity. Furthermore, concern on HBV reactivation is rising as immunosuppressive drug therapies are increasingly been used for cancers and other non-malignant conditions. In this scenario, new challenges are emerging in the management of hepatitis B in HIV-positive individuals. Among them, major interest is focused on failures to suppress HBV replication, HBV breakthroughs and reactivations, the meaning of isolated anti-HBc, screening for liver cancer, and the complexity arising when hepatitis viruses C and/or D are additionally present. This review will focus on these challenges and the major advances in HBV coinfection in HIV. PMID- 26156572 TI - Pentatrichomonas hominis in laboratory-bred common marmosets. AB - Trichomonadid protozoa have been found in the intestinal tracts of common marmosets (Callithrix jacchus). However, there is little information available on species identification and the pathogenicity of these trichomonads. In this study, we conducted a fecal survey of a common marmoset colony maintained as laboratory animals in Japan and identified the trichomonad species. Screening using a fecal smear examination revealed that 66% (58/88) of the marmosets had trichomonadid trophozoites in their feces. The trichomonads were found in both normal feces (31/49, 63%) and diarrhea (27/39, 69%), with no significant difference in frequency. The protozoa were identified as Pentatrichomonas hominis using morphological characters and the 100% identity of the nucleotide sequence of the partial 18S rRNA gene (297 bp). The intraspecific genetic variability between P. hominis from the marmosets in this study and P. hominis from other reported mammal hosts was <=1% in the nucleotide sequence, including the internal transcribed spacer (ITS)-1, 5.8S rRNA gene, and ITS-2 (293 bp). P. hominis inhabits the large intestine of various mammalian hosts, including primates, and is considered nonpathogenic. These results suggest that P. hominis is transmitted among marmosets and other mammals but is not a primary cause of bowel disease in marmosets. PMID- 26156573 TI - Multiscaling Approach for Non-Destructive Adhesion Studies of Metal/Polymer Composites. AB - The adhesion of polyamide 6 (PA6) and polyethylene (PE) toward an aluminum alloy (Al-A) and a dual phase steel (DPS) is studied by contact angle (CA) measurements and atomic force microscopy (AFM). With the combination of the two methods the adhesion properties on a macro- and (sub)microscopic scale can be determined in a nondestructive way. The work of adhesion per area (Wad) of the studied metal/polymer hybrids qualitatively scales the same on both length scales, that is, Al-A/PA6 > DPS/PA6 > Al-A/PE, DPS/PE. The polymer dominates the adhesion. The lower adhesion for PE toward the metal surfaces is explained by dominating van der Waals attraction forces, whereas adhesion for PA6 can also be attributed to attractive polar forces such as hydrogen bonding. For metal/PA6, Wad on a macro- and microscopic length scale is similar. For metal/PE, a discrepancy is measured with lower adhesion values on the microscopic scale than on the macroscopic scale. PMID- 26156574 TI - Before Cumulative Culture : The Evolutionary Origins of Overimitation and Shared Intentionality. AB - In the 7 million years or so since humans shared a common ancestor with chimpanzees we have colonized more of the planet's terrestrial habitat than any other mammalian species and come to account for more biomass than all other terrestrial vertebrates combined. Chimpanzees, in contrast to and under pressure from ourselves, have veered toward extinction. There are multiple reasons for the stark evolutionary trajectories humans and chimpanzees have taken. Recent theoretical and empirical interest has focused on the emergence of cumulative culture whereby technological innovations are progressively incorporated into a population's stock of skills and knowledge, generating ever more sophisticated repertoires. Here we look at the role of high-fidelity imitation and intention reading in the establishment of cumulative culture. By focusing on the lithic record, we aim to identify when in our evolutionary history these skills became part of our ancestors' behavioral repertoire. We argue that evidence of cooperative construction in stone tool manufacture, along with speculation regarding changes to the mirror neurone system, hint at the foundations of overimitation and shared intentionality around 2 million years ago. However, these are not the only ingredients of cumulative culture, which is why we do not see convincing evidence for it until slightly more than a million years later. PMID- 26156575 TI - Clarithromycin regresses endometriotic implants in rat endometriosis model. AB - The aim of this study was to investigate the effect of clarithromycin in rat endometriosis and its association with matrix metalloproteinase-9 (MMP-9) expression. After surgical induction of endometriosis, 27 rats were randomised into three groups. Size of endometriotic implants were evalutated and rats in group I (n = 9) were given 100 mg/kg/day of oral clarithromycin, rats in group II (n = 9) were given single 1 mg/kg s.c. injection of leuprolide acetate and rats in group III (n = 9) were not given any medication for 21 days. At the end of 21 days of medication, remaining 23 rats were sacrificed to evaluate morphological and histological features of implants. There was a significant difference between the groups in implant volumes (p = 0.004) before and after medication. Regression of implants were significantly higher in groups I and II than that in control group (p = 0.009 and p = 0.011, respectively). After medication, in group I the implant volume decreased from 62 (12-166) mm(3) to 26 (3-87) mm(3) (p = 0.012) and in group II the volume decreased from 224 (76-1135) mm(3) to 62 (26-101) mm(3) (p = 0.028). There was a significant difference between groups in histopathological score (p = 0.024). The epithelial immunohistochemical score of MMP-9 was significantly lower in group II than that in control group (p = 0.014). In conclusion, clarithromycin regresses endometriotic implants in rats, but not via MMP-9. PMID- 26156577 TI - Stigma, shame and women's limited agency in help-seeking for intimate partner violence. AB - In Tanzania, 44% of women experience intimate partner violence (IPV) in their lifetime, but the majority never seeks help, and many never tell anyone about their experience. Even among the minority of women who seek support, only 10% access formal services. Our research explored the social and structural barriers that render Tanzanian women unable to exercise agency in this critical domain of their lives. We collected qualitative data in three regions of Tanzania through 104 key informant interviews with duty bearers and participatory focus groups with 96 male and female community members. The findings revealed numerous sociocultural barriers to help-seeking, including gendered social norms that accept IPV and impose stigma and shame upon survivors. Because IPV is highly normalised, survivors are silenced by their fear of social consequences, a fear reinforced by the belief that it is women's reporting of IPV that brings shame, rather than the perpetration of violence itself. Barriers to help-seeking curtail women's agency. Even women who reject IPV as a 'normal' practice are blocked from action by powerful social norms. These constraints deny survivors the support, services and justice they deserve and also perpetuate low reporting and inaccurate estimates of IPV prevalence. PMID- 26156578 TI - Immunophilin-protein interactions in Plasmodium falciparum. AB - Immunophilins comprise two protein families, cyclophilins (CYPs) and FK506 binding proteins (FKBPs), and are the major receptors for the immunosuppressive drugs cyclosporin A (CsA) and FK506 (tacrolimus), respectively. Most eukaryotic species have at least one immunophilin and some of them have been associated with pathogenesis of infectious or parasitic diseases or the action of antiparasitic drugs. The human malarial parasite Plasmodium falciparum has 13 immunophilin or immunophilin-like genes but the functions of their products are unknown. We set out to identify the parasite proteins that interact with the major CYPs, PfCYP19A and PfCYP19B, and the FKBP, PfFKBP35, using a combination of co immunoprecipitation and yeast two-hybrid screening. We identified a cohort of putative interacting partners and further investigation of some of these revealed potentially novel roles in parasite biology. We demonstrated that (i) P. falciparum CYPs interacted with the heat shock protein 70, (ii) treatment of parasites with CYP ligands disrupted transport of the rhoptry-associated protein 1, and (iii) PfFKBP35 interacted with parasite histones in a way that might modulate gene expression. These findings begin to elucidate the functions of immunophilins in malaria. Furthermore, the known antimalarial effects of CsA, FK506 and non-immunosuppressive derivatives of these immunophilin ligands could be mediated through these partner proteins. PMID- 26156579 TI - Comparing current fitness center members' perceptions of the motivational climate with non-members. AB - Researchers using an achievement goal theory and caring climate framework have highlighted the connection between fitness center members' climate perceptions and their exercise motivation. However, much of what is known comes from current members, with little known about former and non-members' perceptions. The purpose of this study was to compare current, former, and non-members' perceptions of the motivational climate of a university campus fitness facility. Faculty and staff ( N = 657) at a large American university completed a one-time mixed-methods survey about their perceptions of the motivational climate (i.e. caring climate; preference for caring, task-, ego-involving climate), staff behaviors (i.e. caring, task involving), and usage of their campus fitness facility. Despite usage, quantitative analyses indicated that all participants reported valuing a caring, task-involving climate over a non-caring, ego-involving climate when choosing a fitness center. When asked about the particular fitness center for this study, current members were more likely than former and never users to perceive a caring climate where staff engaged in task-involving behaviors. Content analysis of the qualitative comments revealed that three main themes emerged with regard to perceptions and fell into positive, negative, and neutral categories. Overall, current users were more likely to perceive caring behaviors among the staff such as taking measures to welcome members and supporting their individualized goals. Former and never users were more likely to perceive staff as unhelpful, unwelcoming, and unfriendly. In an effort to remove barriers to physical activity, fitness professionals should consider how their behaviors, interactions, and promotional materials impact individuals' decision of whether to exercise at their fitness facility. The findings include a discussion for fitness staff to consider when creating advertisement and outreach efforts as well as how to foster the most effective climate to attract and retain exercisers. PMID- 26156580 TI - Advancing the health-promoting prison: a call for global action. AB - The global prison population has grown exponentially in all five continents and consistent analysis shows that many diseases, illnesses and long-term conditions are over-represented in the prison population. Despite the myriad of health challenges in the population, the concept and practice of health promotion is both contested and underdeveloped with significant variation in its application in prison systems globally. The purpose of this commentary paper is twofold. The first is to provide a short overview of the health-promoting prison concept which we argue, at present, is a largely Eurocentric idea which has not been adopted on a global scale. Second, the paper makes a case for more global action on prison health promotion and invites further dialogue and discussion amongst the health promotion community. PMID- 26156581 TI - Proteomic analysis of Artemisia annua--towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin. AB - BACKGROUND: MS-based proteomics was applied to the analysis of the medicinal plant Artemisia annua, exploiting a recently published contig sequence database (Graham et al. (2010) Science 327, 328-331) and other genomic and proteomic sequence databases for comparison. A. annua is the predominant natural source of artemisinin, the precursor for artemisinin-based combination therapies (ACTs), which are the WHO-recommended treatment for P. falciparum malaria. RESULTS: The comparison of various databases containing A. annua sequences (NCBInr/viridiplantae, UniProt/viridiplantae, UniProt/A. annua, an A. annua trichome Trinity contig database, the above contig database and another A. annua EST database) revealed significant differences in respect of their suitability for proteomic analysis, showing that an organism-specific database that has undergone extensive curation, leading to longer contig sequences, can greatly increase the number of true positive protein identifications, while reducing the number of false positives. Compared to previously published data an order-of magnitude more proteins have been identified from trichome-enriched A. annua samples, including proteins which are known to be involved in the biosynthesis of artemisinin, as well as other highly abundant proteins, which suggest additional enzymatic processes occurring within the trichomes that are important for the biosynthesis of artemisinin. CONCLUSIONS: The newly gained information allows for the possibility of an enzymatic pathway, utilizing peroxidases, for the less well understood final stages of artemisinin's biosynthesis, as an alternative to the known non-enzymatic in vitro conversion of dihydroartemisinic acid to artemisinin. Data are available via ProteomeXchange with identifier PXD000703. PMID- 26156582 TI - Sex-specific effects of sympatric mitonuclear variation on fitness in Drosophila subobscura. AB - BACKGROUND: A number of recent studies have shown that the pattern of mitochondrial DNA variation and evolution is at odds with a neutral equilibrium model. Theory has suggested that selection on mitonuclear genotypes can act to maintain stable mitonuclear polymorphism within populations. However, this effect largely relies upon selection being either sex-specific or frequency dependent. Here, we use mitonuclear introgression lines to assess differences in a series of key life-history traits (egg-to-adult developmental time, viability, offspring sex-ratio, adult longevity and resistance to desiccation) in Drosophila subobscura fruit flies carrying one of three different sympatric mtDNA haplotypes. RESULTS: We found functional differences between these sympatric mtDNA haplotypes, but these effects were contingent upon the nuclear genome with which they were co-expressed. Further, we demonstrate a significant mitonuclear genetic effect on adult sex ratio, as well as a sex * mtDNA * nuDNA interaction for adult longevity. CONCLUSIONS: The observed effects suggest that sex specific mitonuclear selection contributes to the maintenance of mtDNA polymorphism and to mitonuclear linkage disequilibrium in this model system. PMID- 26156583 TI - Effect of jabuticaba peel extract on lipid oxidation, microbial stability and sensory properties of Bologna-type sausages during refrigerated storage. AB - This study investigated the lipid oxidation and the microbiological and sensory quality of Bologna-type sausages produced with the addition of jabuticaba peel extract (JPE). Instrumental parameters of color (L*, a* and b*), pH, thiobarbituric acid reactive substance (TBARS) values, microbiological profile, and sensory properties were determined during 35 days of storage. The addition of JPE had an effect on pH and protected the samples from color changes during storage. However, JPE had no positive effect on microbial stability during storage. Samples produced with 0.5, 0.75, and 1% JPE had significantly lower TBARS values (P<0.05) compared with the control group. The addition of up to 0.5% JPE did not affect sensory quality, but prevented the decrease of sensory acceptance during storage. Therefore, due to its antioxidant effect JPE can be used in Bologna-type sausages in order to improve the oxidative stability during the shelf life. PMID- 26156585 TI - Pregnancy through the Lens of Iranian Women with HIV: A Qualitative Study. AB - To explore the experience of pregnancy among Iranian women with HIV, 12 HIV infected pregnant women who referred to counseling center for behavioral diseases in Imam Khomeini Hospital were recruited through purposive sampling. Data were collected by face-to-face, semi-structured interview and were analyzed using conventional content analysis method. Four main themes emerged from the data: fear and hope, stigma and discrimination, marital life stability, and trust in God. Despite concerns about mother-to-child transmission of HIV, and uncertain life span, HIV-infected women tended to continue their pregnancy, and having children was viewed as a window of hope for them. PMID- 26156584 TI - Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets. AB - BACKGROUND: Small studies suggest an association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with primary graft failure (GF) following haploidentical stem cell transplantation, but primary graft rejection (GR) was not discriminated from primary poor graft function (PGF). In this study, we aimed to determine the association of DSAs with primary GF, including GR and PGF, in patients who underwent unmanipulated haploidentical blood and marrow transplantation. METHODS: A total of 345 subjects were prospectively recruited and randomly selected as training group (n = 173) and validation group (n = 172). Patient plasma/serum was screened. For HLA antibody positive samples with a median fluorescent intensity (MFI) >500, DSAs were further tested using a LABScreen Single Antigen Kit (One Lambda). RESULTS: A total of 342 patients (99.1%) achieved sustained myeloid engraftment. The median times to neutrophil engraftment and platelet engraftment were 13 days (range, 8-28 days) and 18 days (range, 6-330 days), respectively. The cumulative incidence of primary GF was 6.4 +/- 1.3% and included GR (0.9 +/- 0.5%) and PGF (5.5 +/- .2%). Of the 345 cases tested, 39 (11.3%) were DSA positive. Multivariate models showed that DSAs (MFI >= 10,000) were correlated to primary GR (P < 0.001) and that DSAs (MFI >= 2000) were strongly associated with primary PGF (P = 0.005). All patients were classified into three groups for analysis. Group A included cases that were DSA negative and those with a DSA MFI <2000 (n = 316), group B included cases with a 2000 <= MFI < 10,000 (n = 19), and group C included cases with a MFI >= 10,000 (n = 10). The DSAs were associated with an increased incidence of the primary GF (3.2 vs. 31.6 vs. 60%, for groups A, B, and C, respectively, P < 0.001), transplant-related mortality (TRM) rate (17.2 vs. 14.7 vs. 33.3%, for groups A, B, and C, respectively, P = 0.022), and inferior overall survival (OS, 77.3 vs. 85.3 vs. 44.4%, for groups A, B, and C, respectively, P = 0.015). The primary GF was independently associated with a higher incidence of TRM (P < 0.001), inferior disease-free survival (P < 0.001), and OS (P < 0.001). CONCLUSIONS: The findings confirmed the effect of DSAs on primary GF, including GR and PGF, and survival. Our results suggest incorporating DSAs in the algorithm for haploidentical donor selection. PMID- 26156586 TI - The effects and mechanisms of SLC34A2 in tumorigenesis and progression of human non-small cell lung cancer. AB - BACKGROUND: SLC34A2 with highest expressions in lung, small intestine and kidney encoded a type 2b sodium-dependent phosphate transporter (NaPi-IIb). In lung, SLC34A2 only expressed in the apical membrane of type II alveolar epithelium cells (ATII cells) and played a pivotal role during the fetal lung development and embryonic development. ATII cells acting as multifunctional stem cells might transform into NSCLC after undergoing exogenous or endogenous factors. Increasing evidences showed that the genes performing critical roles during embryogenesis were also expressed during the development of cancer. In addition, recent research found the expression of SLC34A2 had a significant difference between the surgical samples of NSCLC and normal tissues, and SLC34A2 was down-regulated in lung adenocarcinoma cell line A549 and up-regulation expression of SLC34A2 could significantly inhibit cell viability and invasion of A549 in vitro. These results suggested SLC34A2 might play an important role in the development of NSCLC. However, the role of SLC34A2 in tumorigenesis and progression of NSCLC remains unknown. RESULTS: Our study found that SLC34A2 was also significantly down regulated in 14/15 of examined NSCLC tissues. Moreover, we found that expressions of SLC34A2 were reduced in six NSCLC cell lines for the first time. Our result also revealed a dramatic inhibitory effects of SLC34A2 on cell growth, migration and invasion of several NSCLC cell lines. SLC34A2 also strongly inhibited tumor growth and metastasis ability in A549 subcutaneous tumor model and lung metastasis model, respectively. Further studies found that the suppressive effects of SLC34A2 on tumorigenesis and progression might be associated with the down-regulation of related protein in PI3K/Akt and Ras/Raf/MEK signal pathway. CONCLUSIONS: For the first time, our data indicated that SLC34A2 could exert significantly suppressive effects on tumorigenesis and progression of NSCLC. SLC34A2 might provide new insights for further understanding the early pathogenesis of human NSCLC. PMID- 26156587 TI - A novel device for assessing dark adaptation in field settings. AB - BACKGROUND: Aberrant dark adaptation is common to many ocular diseases and pathophysiological conditions, including vitamin A deficiency, cardiopulmonary diseases, and hypoxia. Scotopic vision and pupillary responsiveness have typically been measured using subjective, time-consuming methods. Existing techniques are particularly challenging for use in developing country settings, where vitamin A deficiency remains a major public health problem. Our aim was design a compact, low cost, and easily operated device to assess dark adaptation in the field. METHODS: The Portable Field Dark Adaptometer (PFDA) incorporates a digital camera, a retinal bleaching flash, and a Ganzfeld light source inside a pair of light-obscuring goggles. After a ~10 min period of dark adaption, the infrared camera digitally records afferent pupillary responses to graded light stimuli (-2.9 to 0.1 log cd/m(2)). We tested this device in a variety of field settings to assess: a) ease of use and b) whether test data could clearly and accurately depict the well-known dose-response relationship between light intensity and pupil contraction. A total of 822 videos were collected. We used an open source video analysis software to measure pupil size in pixel units. Pupillary responsiveness was expressed as the percent change in pupil size from pre- to post-light exposure. Box plots, t test, and multi-level mixed effects linear regression modeling were used to characterize the relationship between light intensity and pupillary response. RESULTS: The PFDA was employed with only minor technical challenges in Bangladesh, Kenya, Zambia, and Peru. Our data show a clear linear increase in pupillary constriction with increasing log light intensity. Light intensity was a strong predictor of pupillary response, regardless of baseline pupil size. CONCLUSIONS: The consistent physiological response demonstrated here supports the use of the PFDA as a reliable tool to measure dark adaptation. As a next step, PFDA measurements will be validated against biochemical indicators of vitamin A status and hypoxemia. Ultimately, this new technology may provide a novel approach for nutritional assessment, with potential clinical applications. PMID- 26156588 TI - Transcriptomic Analysis of Musca domestica to Reveal Key Genes of the Prophenoloxidase-Activating System. AB - The proPO system regulates melanization in arthropods. However, the genes that are involved in the proPO system in housefly Musca domestica remain unclear. Thus, this study analyzed the combined transcriptome obtained from M. domestica larvae, pupae, and adults that were either normal or bacteria-challenged by an Escherichia coli and Staphylococcus aureus mixture. A total of 54,821,138 clean reads (4.93 Gb) were yielded by Illumina sequencing, which were de novo assembled into 89,842 unigenes. Of the 89,842 unigenes, based on a similarity search with known genes in other insects, 24 putative genes related to the proPO system were identified. Eight of the identified genes encoded for peptidoglycan recognition receptors, two encoded for prophenoloxidases, three encoded for prophenoloxidase activating enzymes, and 11 encoded for serine proteinase inhibitors. The expression levels of these identified genes were investigated by qRT-PCR assay, which were consistent with expected activation process of the proPO system, and their activation functions were confirmed by the measurement of phenoloxidase activity in bacteria-infected larvae after proPO antibody blockage, suggesting these candidate genes might have potentially different roles in the activation of proPO system. Collectively, this study has provided the comprehensive transcriptomic data of an insect and some fundamental basis toward achieving understanding of the activation mechanisms and immune functions of the proPO system in M. domestica. PMID- 26156589 TI - Both TALENs and CRISPR/Cas9 directly target the HBB IVS2-654 (C > T) mutation in beta-thalassemia-derived iPSCs. AB - beta-Thalassemia is one of the most common genetic blood diseases and is caused by either point mutations or deletions in the beta-globin (HBB) gene. The generation of patient-specific induced pluripotent stem cells (iPSCs) and subsequent correction of the disease-causing mutations may be a potential therapeutic strategy for this disease. Due to the low efficiency of typical homologous recombination, endonucleases, including TALENs and CRISPR/Cas9, have been widely used to enhance the gene correction efficiency in patient-derived iPSCs. Here, we designed TALENs and CRISPR/Cas9 to directly target the intron2 mutation site IVS2-654 in the globin gene. We observed different frequencies of double-strand breaks (DSBs) at IVS2-654 loci using TALENs and CRISPR/Cas9, and TALENs mediated a higher homologous gene targeting efficiency compared to CRISPR/Cas9 when combined with the piggyBac transposon donor. In addition, more obvious off-target events were observed for CRISPR/Cas9 compared to TALENs. Finally, TALENs-corrected iPSC clones were selected for erythroblast differentiation using the OP9 co-culture system and detected relatively higher transcription of HBB than the uncorrected cells. This comparison of using TALENs or CRISPR/Cas9 to correct specific HBB mutations in patient-derived iPSCs will guide future applications of TALENs- or CRISPR/Cas9-based gene therapies in monogenic diseases. PMID- 26156590 TI - James Cave: Torn to shreds by Sister Harvey. PMID- 26156591 TI - A PBPK model describing a xenobiotic with a short PK event scale. AB - Physiologically-based pharmacokinetic (PBPK) modeling has been widely used in human risk assessment and in early drug development to predict human PK from in vitro and/or in vivo animal data. Recently, the application of PBPK modeling has been extended to the evaluation of drug-drug interactions. For most xenobiotic agents, the PK event scale such as elimination is in hours or days. This is much longer than the transit time of the agent in the body, and a PBPK model can be significantly simplified through lumping based on the physiochemical properties, mass transfer, and biotransformation. However, for a xenobiotic agent with a short PK event scale, e.g. in minutes, such an approach is not applicable. In this manuscript, the authors used the observed PK data from an ultrasound contrast agent to illustrate the role of a short PK event scale in the development of a suitable PBPK model. The model development process showed that a PBPK model assuming uniform venous and arterial blood pools, with a static lung model including alveolar and tissue regions, was unable to adequately capture the characteristics of the PK of the agent. Detailed information describing the pulmonary and cardiovascular circulation, and a heterogeneous dynamic lung model became necessary for the model. This exercise once again demonstrates the importance of the principles and methodologies that have been established since the 1960s that need to be followed during PBPK model development. PMID- 26156592 TI - Clinical significance of fluctuations in thyroid hormones after surgery for Cushing's syndrome. AB - Patients with Cushing's syndrome (CS) frequently develop hyperthyroidism after surgery due to SITSH (syndrome of inappropriate secretion of TSH) and this SITSH contributed to the symptoms of steroid withdrawal syndrome (SWS). However, the duration of fluctuations in thyroid hormones after surgery for CS remains unknown. The aim of this prospective study was to investigate the clinical course of fluctuation in thyroid hormone level in CS patients after surgery. Thyroid hormone levels [free T3 (FT3), free T4 (FT4) and TSH] and serum cortisol levels were measured before and 1, 3, 6 and 12 months after surgery in 8 patients with active CS (3 pituitary CS and 5 adrenal CS). FT3 levels were above the normal range in 75% of patients up to 6 months after surgery, but returned to the normal range by 12 months. However, TSH levels were not suppressed below the normal range throughout the first 12 months after surgery. Serious symptoms of SWS appeared during the 6-month period after surgery, but disappeared with normalization of thyroid function at 12 months, which was not related to the recovery of function hypothalamus-pituitary-adrenal axis after CS surgery. Therefore, T3 toxicosis could result in deterioration of SWS after surgery for CS. These results indicate that physicians need to take T3 toxicosis into consideration in the pathological evaluation of SWS within 12 months after surgery for CS. PMID- 26156593 TI - Serum fetuin-A concentrations are positively associated with serum VEGF levels in patients with newly diagnosed type 2 diabetes. AB - Fetuin-A was considered to be involved in pathogenesis of type 2 diabetes. On the other hand, higher vascular endothelial growth factor (VEGF) expression is associated with diabetes and its vascular complications, but the mechanisms leading to higher VEGF levels are still not clear. To the best of our knowledge, there are no data to show the associations between fetuin-A and VEGF in patients with type 2 diabetes. Therefore, the aim of this study is to investigate the relationship between serum fetuin-A concentrations and serum VEGF levels in patients with type 2 diabetes. We recruited 345 patients with newly diagnosed type 2 diabetes. Serum fetuin-A concentrations and serum VEGF levels were measured using enzyme-linked immunosorbent assay (ELISA) method. In this study, there was a significant positive correlation between serum fetuin-A concentrations and serum VEGF levels (r=0.223, P<0.001), and the correlation remained significant even after adjustment for other confounding factors in the multivariate regression model (beta=0.151, P=0.006). Mantel-Haenszel (M-H) stratified analysis showed that the degree of association of high concentrations of fetuin-A with high levels of VEGF is higher than that with low levels of VEGF (odds ratio of M-H [ORM-H], 2.938; 95% confidence interval [CI], 1.896-4.553). In addition, this study showed that both fetuin-A and VEGF were positively associated with fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c) and C-reactive protein (CRP). These data suggested that serum fetuin-A concentrations were positively associated with serum VEGF levels in patients with newly diagnosed type 2 diabetes. PMID- 26156594 TI - Training must be fit for purpose. PMID- 26156596 TI - Move to raise awareness of anaphylaxis caused by bee and wasp stings. PMID- 26156597 TI - Perinatal death figures prompt call to end postcode lottery of care. PMID- 26156598 TI - College urged to lobby ministers on reducing health inequalities. PMID- 26156599 TI - Lack of resources hinders palliative care. PMID- 26156600 TI - Better training will reduce asthma prescribing risks. PMID- 26156601 TI - Generic training will not prepare nurses of right calibre to care for children and families. PMID- 26156606 TI - Research essentials. Understanding the principles of data analysis. PMID- 26156607 TI - Research and commentary. Vital to explore any potential or actual psychosocial consequences. PMID- 26156609 TI - Guidelines on blended diet. PMID- 26156610 TI - Starting out--A case that made me stronger. PMID- 26156611 TI - Employers need to join the 21st century. PMID- 26156612 TI - Exploring the reasons why school students eat or skip breakfast. AB - BACKGROUND: Breakfast is considered to be the most important meal of the day. It provides the essential nutrients needed for the day's activities. AIMS: To determine the prevalence of breakfast consumption and to assess the nutritional status of students aged 12-18 years. METHODS: A school-based study carried out between September and October 2014 involved 1,303 school students from grades 7 to 12, aged 12 to 18 years, who completed a questionnaire on breakfast consumption. The chi-square test was used. An odds ratio and 95% confidence interval determined the predictive factors for skipping breakfast. RESULTS: The prevalence of breakfast consumption was 52.3%, statistically decreasing with age. Adjusted logistic regression analysis reflected a statistically high consumption among 12-15 year olds, those with highly educated mothers and those with low family income. CONCLUSION: For the target groups at risk, a community and school based health education programme, conducted by school nurses and other healthcare providers, would be beneficial. PMID- 26156613 TI - Challenges of identifying eczema in darkly pigmented skin. AB - There is a paucity of information about the difference in the presentation of eczema in darkly pigmented skin compared to children with fair or white skin. This article describes the possible challenges of diagnosing eczema in children with darkly pigmented skin. The physiological difference in darkly pigmented skin compared with fair or white skin is explored, and how eczema may be manifested and identified in darkly pigmented skin. The author uses the term darkly pigmented skin to describe children of black Caribbean, African or Asian descent. PMID- 26156614 TI - An introduction to growth and atypical growth in childhood and adolescence. AB - This is the first of a series of continuing professional development articles that provide insight into the sphere of practice of paediatric endocrinology nurse specialists. The article is aimed at registered nurses and nursing students who are interested in reviewing their knowledge of normal childhood growth and exploring potential reasons for, and consequences of, atypical growth. It discusses the stages and physiology of growth through childhood and adolescence. There is a focus on auxology, reviewing usual and more specialist measurement and assessment techniques used to collect data on a child's growth. Potential causes of atypical growth are explored, which may present as tall or short stature, requiring referral to specialist services. PMID- 26156615 TI - Management of a solitary pulmonary arteriovenous malformation by video-assisted thoracoscopic surgery and anatomic lingula resection: video and review. AB - BACKGROUND: Pulmonary arteriovenous malformations are abnormal communications between the pulmonary arterial and venous vasculature leading to a right-to-left blood shunt. Based on possible complications, including hypoxemia, hemorrhage, infection and paradoxical embolism, deactivation of the malformation from the circulation is the treatment option of choice, either by interventional embolization or by surgery. Embolization is less invasive and has widely replaced surgery, but bears the risk of revascularization, recanalization and downstream migration of the device with paradoxical embolism. METHODS: We report on the case of a 76-year-old male patient suffering from a complex, plexiform pulmonary arteriovenous malformation in the lingula, which was treated by video-assisted thoracoscopic surgery and anatomic lingula resection. Patient's medical history, clinical examination and imaging studies did not reveal any evidence of hereditary hemorrhagic telangiectasia. RESULTS: Left-sided anterior three-port video-assisted thoracoscopic surgery (VATS) approach was used. Instead of only wedge resecting the very peripherally located pulmonary arteriovenous malformation, the lingular vessels were controlled centrally and an anatomic lingula resection was performed in order to prevent a more central re malformation. To prevent rupture of the aneurysm sac through pressure overload, the feeding arteries were controlled before the draining vein. Duration of the total procedure was 151 min, the single chest tube was removed on the postoperative day 3, and the patient was discharged on the postoperative day 6. CONCLUSION: Although interventional embolism of the feeding artery of a pulmonary arteriovenous malformation is the current therapeutic gold standard, minimally invasive anatomic lung resection by video-assisted thoracoscopic surgery can be considered, especially for the treatment of solitary large arteriovenous malformations. By anatomic lung resection, the risk of recanalization, collateralization and peri-interventional paradoxical embolism may be reduced. PMID- 26156616 TI - Laparoscopic pancreatoduodenectomy with superior mesenteric artery-first approach and pancreatogastrostomy assisted by mini-laparotomy. AB - BACKGROUND: Laparoscopic pancreatoduodenectomy (LPD) is a complex procedure. Critical steps are achieving a negative retroperitoneal margin and re establishing pancreatoenteric continuity minimizing postoperative pancreatic leak risk. Aiming at increasing the rate of R0 resection during pancreatoduodenectomy, many experienced teams have recommended the superior mesenteric artery (SMA) first approach, consisting in early identification of the SMA at its origin, with further resection guided by SMA anatomic course. We describe our technique of LPD with SMA-first approach and pancreatogastrostomy assisted by mini-laparotomy. METHODS: The video concerns a 77-year-old man undergoing our variant of LPD for a 2.5-cm pancreatic head mass. After kocherization, the SMA is identified above the left renocaval confluence and dissected-free from the surrounding tissue. Dissection of the posterior pancreatic aspect exposes the confluence between splenic vein, superior mesenteric vein (SMV), and portal vein. Following duodenal section, the common hepatic artery is dissected and the gastroduodenal artery sectioned at the origin. The first jejunal loop is divided, skeletonized, and passed behind the superior mesenteric vessel. Following pancreatic transection, the uncinate process is dissected from the SMV and the SMA is cleared from retroportal tissue rejoining the previously dissected plain. Laparoscopic choledocojejunostomy is followed by a mini-laparotomy-assisted pancreatogastrostomy, performed as previously described, and a terminolateral gastrojejeunostomy. RESULTS: Twelve patients underwent our variant of LPD (July 2013-May 2015). Female/male ratio was 3:1, median age 65 years (range 57-79), median operation duration 590 min (580-690), intraoperative blood loss 150 cl (100-250). R0 resection rate was 100 %, and the median number of resected lymph nodes was 24 (22-28). Postoperative complications were grade II in two patients and IIIa in one. Median postoperative length of stay was 16 days (14-21). CONCLUSION: LPD with SMA-first approach with pancreatogastrostomy assisted by a mini-laparotomy well combines the benefits of laparoscopy with low risk of postoperative complications and high rate of curative resection. PMID- 26156617 TI - Endoscopic and oncologic outcomes according to indication criteria of endoscopic resection for early gastric cancer: a systematic review and meta-analysis. AB - BACKGROUND: The criteria for endoscopic resection for early gastric cancer (EGC) have been expanded recently, and it has become acceptable to use techniques that are regarded as having equivalent technical and pathological outcomes to absolute indication (AI). However, the long-term oncological outcomes of expanded indication (EI) have yet to be clarified. This meta-analysis aimed to assess the long-term outcome of EI versus AI, to identify the endoscopic feasibility and safety according to the indication, and to provide the appropriate recommendations for each indication. METHODS: Electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and KoreaMed were searched for articles published between January 2000 and October 2014. After screening, the reviewers extracted the information from 12 retrospective cohort studies. A total of 9635 EGC lesions, 4150 lesions in the EI group and 5485 lesions in the AI group, were included in this study. RESULTS: Meta-analyses showed that the local recurrence rate [risk ratio (RR) 1.34; 95% CI 0.67-2.70] was not significantly higher in the EI group compared with the AI group, although the metachronous recurrence rate was higher in the EI group than in the AI group (RR 1.60; 95% CI 1.22-2.10). The rates of en bloc resection [odds ratio (OR) 0.57; 95% CI 0.41-0.78), complete resection (OR 0.37; 95% CI 0.25-0.57), and curative resection (OR 0.34; 95% CI 0.20-0.58) were significantly inferior in the EI group than in the AI group, whereas overall bleeding risk (RR 1.47; 95% CI 1.19-1.82) and procedure-related perforation rate (OR 2.04; 95% CI 1.56-2.68) were significantly higher in the EI group than in the AI group. CONCLUSIONS: This meta-analysis suggests that the EI group showed acceptable long-term outcomes with local recurrence rate that was not significantly inferior, although the metachronous recurrence rate was higher compared with that in the AI group. PMID- 26156618 TI - Beyond decreased bowel enhancement: acute abnormalities of the mesenteric and portal vasculature. AB - Acute mesenteric ischemia (AMI) is a potentially life-threatening condition with an associated high mortality. Prompt diagnosis is crucial to achieve a favorable outcome. The radiologist plays a central role in the initial evaluation of a patient with suspected AMI. In this pictorial essay, we review the appropriate imaging evaluation of a patient with suspected AMI, and we review both the common and uncommon etiologies of mesenteric ischemia. With each etiology presented, relevant clinical and imaging findings, as well as potential treatments, are reviewed. PMID- 26156619 TI - DWI-associated entire-tumor histogram analysis for the differentiation of low grade prostate cancer from intermediate-high-grade prostate cancer. AB - PURPOSE: To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate-high-grade (HG) PCa in comparison with conventional ROI-based measurement. METHODS: DW images (b of 0-1400 s/mm(2)) from 126 pathology confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS <= 6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar's test. RESULTS: There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (rho = -0.225 to -0.406, p < 0.05). All above imaging indices reflected significant difference between LG-PCa and HG-PCa (all p values <0.01). Histogram 10th ADCs had dominantly high Az (0.738), Youden index (0.415), and positive likelihood ratio (LR+, 2.45) in stratifying tumor GS against mean, median and 90th ADCs, and ROI-based ADCs. Histogram mean, median, and 10th ADCs showed higher specificity (65.3%-74.1% vs. 44.9%, p < 0.01), but lower sensitivity (57.1%-71.3% vs. 84.4%, p < 0.05) than ROI-based ADCs in differentiating LG-PCa from HG-PCa. CONCLUSIONS: DWI-associated histogram analysis had higher specificity, Az, Youden index, and LR+ for differentiation of PCa Gleason grade than ROI-based approach. PMID- 26156620 TI - Molecular characterization of the circulating Bacillus anthracis in Jordan. AB - To understand the biomolecular charcteristics of Bacillus anthracis in Jordan, 20 blood smear slides from dead animals with suspected anthrax were analyzed using conventional and molecular approaches. All slides were positive for B. anthracis by conventional staining but no growth of the organism on selective media was detected. However, of the 20 samples, 16 were B. anthracis DNA-positive using polymerase chain reaction (PCR). Seven samples provided enough quantity and quality of DNA, and their multilocus variable tandem repeat analysis (MLVA)-15 loci analysis revealed two different genotypes. All genotypes were belonging to A.B..r. 008/009 which is very common in Asia and Europe. Single nucleotide repeat (SNR) analysis revealed that there were no sub genotypes. Molecular diagnosis of animal anthrax in Jordan is not used routinely; henceforth, official diagnosis of anthrax is based on the observation of the slides by optical microscope and this can often cause reading errors. Therefore, the prevalence of the disease in Jordan might be slightly lower than that reported by the official bodies. PMID- 26156621 TI - Single cell super-resolution imaging of E. coli OmpR during environmental stress. AB - Two-component signaling systems are a major strategy employed by bacteria, and to some extent, yeast and plants, to respond to environmental stress. The EnvZ/OmpR system in E. coli responds to osmotic and acid stress and is responsible for regulating the protein composition of the outer membrane. EnvZ is a histidine kinase located in the inner membrane. Upon activation, it is autophosphorylated by ATP and subsequently, it activates OmpR. Phosphorylated OmpR binds with high affinity to the regulatory regions of the ompF and ompC porin genes to regulate their transcription. We set out to visualize these two-components in single bacterial cells during different environmental stress conditions and to examine the subsequent modifications to the bacterial nucleoid as a result. We created a chromosomally-encoded, active, fluorescent OmpR-PAmCherry fusion protein and compared its expression levels with RNA polymerase. Quantitative western blotting had indicated that these two proteins were expressed at similar levels. From our images, it is evident that OmpR is significantly less abundant compared to RNA polymerase. In cross-sectional axial images, we observed OmpR molecules closely juxtaposed near the inner membrane during acidic and hyposomotic growth. In acidic conditions, the chromosome was compacted. Surprisingly, under acidic conditions, we also observed evidence of a spatial correlation between the DNA and the inner membrane, suggesting a mechanical link through an active DNA-OmpR EnvZ complex. This work represents the first direct visualization of a response regulator with respect to the bacterial chromosome. PMID- 26156622 TI - Epstein-Barr virus-positive T-cell-associated colitis mimicking inflammatory bowel disease: clinicopathological study of two cases. PMID- 26156623 TI - New phenyl derivatives from endophytic fungus Botryosphaeria sp. SCSIO KcF6 derived of mangrove plant Kandelia candel. AB - Two new phenyl derivatives (1 and 3), along with two new natural products (4 and 5), and three known compounds (2, 6 and 7), were isolated from an endophytic fungus Botryosphaeria sp. SCSIO KcF6. The structures of these compounds 1-7 were elucidated by the extensive 1D and 2D-NMR and HRESIMS Data analysis, and compared with those of reported data. The absolute configuration of the compounds 1 and 3 were assigned by optical rotation and CD data. The isolated compounds were evaluated for their cytotoxic, anti-inflammatory (COX-2) and antimicrobial activities. Compound 3 exhibited a specific COX-2 inhibitory activity with the IC50 value of 1.12 MUM. PMID- 26156624 TI - Pioglitazone Reduces Vascular Lipid Accumulation in Angiotensin II-Induced Hypertensive Rat. AB - AIM: In an insulin-resistant state, excess lipids may accumulate in various non adipose tissues, leading to histological and functional damage. It has been suggested that peroxisome proliferator-activated receptor-gamma (PPARgamma) may ameliorate disorganized lipid balance. In the current study, we analyzed whether pioglitazone, an agonist of PPARgamma, reduces angiotensin II-induced vascular lipid accumulation. METHODS: Angiotensin II was infused into rats at doses of 0.7 mg/kg/day via a subcutaneously implanted osmotic minipump for 7 consecutive days. Pioglitazone was orally given at a dose of 2.5 mg/kg/day for 7 days. RESULTS: Pioglitazone significantly reduced angiotensin II-induced enhanced lipid deposition and superoxide production in the adventitia of the aorta, as detected by oil red O and dihydroethidium (DHE) staining, respectively. Increased DHE signals, some observed at the site of lipid deposition, were mainly localized in ED-1-positive monocytes/macrophages. Angiotensin II-induced upregulation of the expression of LDL receptor and Nox1 was inhibited by pioglitazone treatment. In addition, angiotensin II significantly reduced the expression of PCSK9, and this reduction was ameliorated by pioglitazone. On the other hand, pioglitazone did not significantly alter the expression of the phosphorylated forms of AMPKalpha and ACC, which was downregulated by angiotensin II. CONCLUSIONS: Pioglitazone treatment suppressed excess lipid accumulation and superoxide production in the aorta in an angiotensin II-induced rat model of hypertension. PMID- 26156625 TI - A Trial of Pitavastatin Versus Rosuvastatin for Dyslipidemia in Chronic Kidney Disease. AB - AIM: To determine the lipid lowering effectiveness, cost effectiveness, and safety of rosuvastatin compared with pitavastatin in dyslipidemic patients with concurrent renal disorders. METHODS: This single-center, prospective, open-label, randomized, 12-month study evaluated rosuvastatin (2.5 mg) and pitavastatin (1 or 2 mg) in 134 dyslipidemic patients with concurrent chronic kidney disease (CKD; rosuvastatin group, n=68; pitavastatin group, n=66). Lipid parameters [i.e., low density lipoprotein cholesterol (LDL-C), etc.], renal function parameters [i.e., estimated glomerular filtration rate (eGFR), etc.], glycated hemoglobin (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (baseline), month 6, and month 12. RESULTS: The mean daily dose of rosuvastatin and pitavastatin was 2.5 mg and 1.4 mg, respectively. All lipid parameters were significantly more improved in the rosuvastatin group. eGFR improved from baseline in the rosuvastatin group (p < 0.0001) and showed no tendency to worsen in the pitavastatin group (p=0.2232). In multiple regression analysis (n=134), it was significantly associated with a percent change in total cholesterol (beta=0.2296; p=0.0112), smoking (beta=0.1927; p=0.0224), and HbA1c (beta= 0.1606; p=0.0585). Hs-CRP was significantly improved in both groups. An analysis eliminating the influence of antidiabetic medication showed a significant difference between groups in the change of HbA1c at month 6 from baseline (p=0.0016). No subjects in either group had new onset of diabetes mellitus. The cost of statin medication required to reduce LDL-C by 10 mg/dL was significantly lower for 2.5 mg of rosuvastatin (p=0.0116). CONCLUSIONS: Rosuvastatin 2.5 mg had superior lipid lowering and cost effectiveness in dyslipidemic patients with concurrent CKD.(UMIN ID: UMIN000005812). PMID- 26156626 TI - Psychometric properties of the Adolescent Dissociative Experiences Scale in a sample of Italian adolescents. AB - The purpose of this study was to examine the psychometric properties of the Italian translation of the Adolescent Dissociative Experiences Scale (A-DES). A sample of 1,806 high-school students between the ages of 13 and 18 years, recruited in 6 Italian cities, completed the A-DES. The A-DES showed high internal consistency, excellent item-to-scale homogeneity, good split-half reliability, and a single-factor structure. The scores of the Italian adolescents were comparable to those found in previous research with the measure. No gender differences were found in mean A-DES scores, but boys and girls showed different patterns of responses on A-DES items. Age differences were also found, with 13- and 18-year-old students scoring higher on the measure than the other participants. A cluster analysis showed that participants could be consistently grouped into 2 clusters of low- and high-dissociative adolescents. This study supports the A-DES as a reliable and valid screening measure for dissociative symptoms in adolescents. PMID- 26156628 TI - Dual function of a bacterial protein as an adhesin and extracellular effector of host GTPase signaling. AB - Bacterial pathogens often target conserved cellular mechanisms within their hosts to rewire signaling pathways and facilitate infection. Rho GTPases are important nodes within eukaryotic signaling networks and thus constitute a common target of pathogen-mediated manipulation. A diverse array of microbial mechanisms exists to interfere with Rho GTPase signaling. While targeting of GTPases by secreted bacterial effectors is a well-known strategy bacterial pathogens employ to interfere with the host, we have recently described pathogen adhesion as a novel extracellular stimulus that hijacks host GTPase signaling. The Multivalent Adhesion Molecule MAM7 from Vibrio parahaemolyticus directly binds host cell membrane lipids. The ensuing coalescence of phosphatidic acid ligands in the host membrane leads to downstream activation of RhoA and actin rearrangements. Herein, we discuss mechanistic models of lipid-mediated Rho activation and the implications from the infected host's and the pathogen's perspective. PMID- 26156627 TI - Lung inflammation and lack of genotoxicity in the comet and micronucleus assays of industrial multiwalled carbon nanotubes Graphistrength((c)) C100 after a 90 day nose-only inhalation exposure of rats. AB - BACKGROUND: Graphistrength ((c)) C100 multiwalled carbon nanotubes (MWCNT) provide superior electrical and mechanical properties for various applications. The evaluation of the intrinsic hazard properties of Graphistrength((c)) C100 is an essential step for safe use. A general feature of multiwalled carbon nanotubes after inhalation or intratracheal exposures is the induction of an inflammatory reaction in the lungs sometimes associated with local genotoxic effects. METHODS: After investigating different parameters for the aerosol generation and performing a 5-day inhalation range finding study, male and female Wistar rats were exposed nose-only for 90 days to target concentrations of 0.05, 0.25 and 5.0 mg/m(3) air of Graphistrength ((c)) C100 and sacrificed 24 h and 90 days after the last exposure. Broncho-alveolar lavage fluid (BALF) was also collected and analyzed for inflammatory parameters. Twenty-four hours post-exposure, chromosomal aberrations in the bone marrow cells were evaluated by the micronucleus test and DNA damages in the lung, kidney and liver cells by both the standard and the human 8-oxoguanine DNA N-glycosylase 1 (hOGG1)-modified comet assay. All studies were performed according to the OECD test guidelines. RESULTS: An inflammatory lung reaction and the release of inflammatory factors in the BALF were observed in all rats exposed to 5.0 mg/m(3), associated with changes in the differential white blood cells counts. The slight changes in BALF parameters at 0.25 mg/m(3) recovered and signs of lung clearance of the MWCNT were observed. No pathological changes were observed on the pleura. Neither increase in the number of micronucleated polychromatic erythrocytes nor increase in percent DNA damage were observed at any concentration. CONCLUSIONS: Lung inflammation characteristic of an overload with insoluble particles was observed after a 90-day exposure to 5.0 mg/m(3) of Graphistrength ((c)) C100. Clear signs of clearance and recovery were observed at 0.25 mg/m(3). No genotoxicity was detected locally in lung and distally in bone marrow, liver and kidney. Therefore, Graphistrength ((c)) C100 appears of low concern in term of local and systemic genotoxicity and a No Observed Adverse Effect Concentration (NOAEC) of 0.25 mg/m(3) (0.28 mg/m(3) as actual concentration) was established for the repeated-dose toxicity. PMID- 26156629 TI - The Cost of Smoking in California. AB - INTRODUCTION: The economic impact of smoking, including healthcare costs and the value of lost productivity due to illness and mortality, was estimated for California for 2009. METHODS: Smoking-attributable healthcare costs were estimated using a series of econometric models that estimate expenditures for hospital care, ambulatory care, prescriptions, home health care, and nursing home care. Lost productivity due to illness was estimated using an econometric model predicting how smoking status affects the number of days lost from work or other activities. The value of lives lost from premature mortality due to smoking was estimated using an epidemiological approach. RESULTS: Almost 4 million Californians still smoke, including 146 000 adolescents. The cost of smoking in 2009 totaled $18.1 billion, including $9.8 billion in healthcare costs, $1.4 billion in lost productivity from illness, and $6.8 billion in lost productivity from premature mortality. This amounts to $487 per California resident and $4603 per smoker. Costs were greater for men than for women. Hospital costs comprised 44% of healthcare costs. CONCLUSIONS: Despite extensive efforts at tobacco control in California, healthcare and lost productivity costs attributable to smoking remain high. Compared to costs for 1999, the total cost was 15% greater in 2009. However, after adjusting for inflation, real costs have fallen by 13% over the past decade, indicating that efforts have been successful in reducing the economic burden of smoking in the state. PMID- 26156630 TI - Beclabuvir for the treatment of hepatitis C. AB - INTRODUCTION: About 185,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). Currently, the most successful HCV infection antiviral therapies reduce the chance of progression towards the advanced phases of the hepatopathy (liver cirrhosis, hepatocellular carcinoma and death). Recently, however, several new direct-acting antivirals against HCV are available or are in an advanced phase of clinical development. AREAS COVERED: This review focuses on beclabuvir , an allosteric non-nucleotide inhibitor of HCV polymerase. The article covers its pharmacokinetics, mechanism of action, in addition to its tolerability and safety profile as well as its resistance pattern. EXPERT OPINION: The pharmacokinetic, efficacy and tolerability profile of beclabuvir, as well as its barrier to resistance, are very favorable. In particular, the combination of beclabuvir with asunaprevir and daclatasvir achieves very high rates of viral eradication (about 90%) in patients infected with HCV genotype 1, which is the most common genotype worldwide. Therefore, beclabuvir represents a powerful weapon against HCV infection and has to be considered an optimal option in tailored IFN-free combinations. PMID- 26156632 TI - Trimethoprim-sulfamethoxazole monotherapy should not be used for treatment of severe methicillin-resistant Staphylococcus aureus infections. PMID- 26156631 TI - TOL19-001 reduces inflammation and MMP expression in monolayer cultures of tendon cells. AB - BACKGROUND: Tendinopathies are tendon conditions associated with degeneration and disorganization of the matrix collagen fibers, tendon cells apoptosis and inflammation through up-regulation of proinflammatory cytokines, matrix metalloproteinase (MMP) expression, and prostaglandin E2 (PGE2) production. Currently, the pharmacological treatment is mainly based on non-steroidal anti inflammatory drugs (NSAIDs) use and corticosteroid injections, which both can lead to numerous side effects for patients. TOL19-001 is a diet supplementary composed mostly of spirulina and glucosamine sulfate whose antioxidant properties could be helpful to treat tendinopathies while avoiding taking NSAIDs. In this study we developed an in vitro model of tendinopathy in order to evaluate the therapeutic potential of TOL19-001. METHODS: Tendon cells were cultured on monolayer and treated with interleukin-1beta (IL-1beta) or ciprofloxacin (CIP), and then, MMPs, PGE2 and collagen expression was evaluated by RT-PCR or Elisa. In addition, a cotreatment with increased doses of TOL19-001 was done. Toxicity of TOL19-001 was evaluated using a metabolic activity assay. RESULTS: This study demonstrates that IL-1beta mimics some aspects of tendinopathies with PGE2 induction, MMP expression (mostly MMP1 and MMP3), and increases of type III/I collagen ratio. CIP, meanwhile, leads to an increase of MMP2 and p65 mRNA, whereas it reduces TIMP1 expression. Scleraxis expression was also increased by CIP whereas it was decreased by IL-1beta treatment. Besides, TOL19-001 cotreatment suppresses tendon cell inflammation in vitro, marked by the downregulation of PGE2, MMPs and type III collagen in IL-1beta stimulated-cells. TOL19-001 also represses CIP induced-changes. CONCLUSIONS: These findings indicate that TOL19-001 exerts anti-inflammatory effects on tendon cells, which might explain why TOL19-001 diet may improve tendon function in patients with tendon injury. Future research is required to determine TOL19-001 effect on injured or overused tendons in vivo. PMID- 26156633 TI - REST represses a subset of the pancreatic endocrine differentiation program. AB - To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3(+) progenitors, decreases beta and alpha cell mass by E18.5, and triggers diabetes in adulthood. Conditional inactivation of Rest in Pdx1(+) progenitors is not sufficient to trigger endocrine differentiation but up-regulates a subset of differentiation genes. Our results show that the transcriptional repressor REST is active in pancreas progenitors where it gates the activation of part of the beta cell differentiation program. PMID- 26156634 TI - Changes in circulating leptin levels during the initial stage of cessation are associated with smoking relapse. AB - RATIONALE: Leptin has been linked to tobacco craving and withdrawal-related symptoms. Very few studies have examined leptin prospectively in both male and female nonsmokers and smokers. OBJECTIVES: We examine leptin concentrations prospectively in both male and female nonsmokers and smokers to assess the associations of leptin with psychological symptoms and smoking relapse during ad libitum smoking, the first 48 h post quit, and 4 weeks post-cessation. METHODS: Self-report psychological, anthropomorphic, and biological measures (cotinine, carbon monoxide, and plasma leptin) were collected before and after 48 h of smoking abstinence. Smokers were stratified at 28 days post quit as abstinent or relapsed if they had smoked daily for seven consecutive days at any point in the 28 days. RESULTS: Leptin concentration (square root transformed ng/ml) increased over the 48-h abstinence, but only in female abstainers. In contrast, leptin was very stable across time for nonsmokers, relapsers, and males. Cox regression supported that increased leptin was associated with decreased risk of relapse. Leptin was correlated negatively with withdrawal symptoms for abstainers only. Females produce more leptin than males and this level increases from ad libitum smoking to 48-h post quit. CONCLUSIONS: The current analysis indicates that a leptin increase early in cessation predicts abstinence. The increase in women, but not men, in response to abstinence provides further evidence of important gender differences. The negative correlation between leptin and withdrawal symptoms indicates a possible protective effect of leptin. Further research is ongoing to elucidate the psychological and biological determinants of this effect. PMID- 26156635 TI - Aberrant approach-avoidance conflict resolution following repeated cocaine pre exposure. AB - RATIONALE: Addiction is characterized by persistence to seek drug reinforcement despite negative consequences. Drug-induced aberrations in approach and avoidance processing likely facilitate the sustenance of addiction pathology. Currently, the effects of repeated drug exposure on the resolution of conflicting approach and avoidance motivational signals have yet to be thoroughly investigated. OBJECTIVE: The present study sought to investigate the effects of cocaine pre exposure on conflict resolution using novel approach-avoidance paradigms. METHODS: We used a novel mixed-valence conditioning paradigm to condition cocaine pre-exposed rats to associate visuo-tactile cues with either the delivery of sucrose reward or shock punishment in the arms in which the cues were presented. Following training, exploration of an arm containing a superimposition of the cues was assessed as a measure of conflict resolution behavior. We also used a mixed-valence runway paradigm wherein cocaine-pre-exposed rats traversed an alleyway toward a goal compartment to receive a pairing of sucrose reward and shock punishment. Latency to enter the goal compartment across trials was taken as a measure of motivational conflict. RESULTS: Our results reveal that cocaine pre-exposure attenuated learning for the aversive cue association in our conditioning paradigm and enhanced preference for mixed-valence stimuli in both paradigms. CONCLUSIONS: Repeated cocaine pre-exposure allows appetitive approach motivations to gain greater influence over behavioral output in the context of motivational conflict, due to aberrant positive and negative incentive motivational processing. PMID- 26156636 TI - Motivational assessment of mice using the touchscreen operant testing system: effects of dopaminergic drugs. AB - RATIONALE: Touchscreens are widely used to examine rodent cognition. Current paradigms require animals to view stimuli and nose poke at an appropriate touchscreen location. After responding, there is little screen interaction and, as infra-red touchscreens eliminate the need for physical contact, minimal somatosensory feedback. It is therefore unclear if touchscreens can support the vigorous, repetitive responding required in paradigms like progressive ratio (PR) for assessing motivation and effort-related choice (ERC) for assessing decision making. OBJECTIVES: This study aims to adapt and validate PR and ERC for the rodent touchscreen. METHODS: Male C57Bl/6 mice were trained until responding on PR stabilised. Amphetamine, sulpiride and raclopride were administered via the intraperitoneal route to modify performance. Mice were transferred to ERC and paradigm parameters adjusted to demonstrate behavioural modification. ERC reward preference was assessed by home cage choice analysis. RESULTS: PR performance stabilised within seven sessions. Amphetamine (1 mg/kg) increased and raclopride (0.3 mg/kg) decreased performance by 63 and 28 %, respectively, with a 20-min injection-test interval. Sulpiride (50 mg/kg) decreased performance by 19 % following a 40-min injection-test interval. Increasing ERC operant requirements shifted responding from the operant response-dependent preferred reward towards the freely available alternative. CONCLUSIONS: Vigorous, repetitive responding is sustainable in touchscreen PR and ERC and task validation mirrors non-touchscreen versions. Thus, motivation and reward-related decision-making can be measured directly with touchscreens and can be evaluated prior to cognitive testing in the same apparatus to avoid confounding by motivational factors. PMID- 26156639 TI - Colorectal cancer: APC restores order. PMID- 26156637 TI - Control of cancer formation by intrinsic genetic noise and microenvironmental cues. AB - Differentiation therapies that induce malignant cells to stop growing and revert to normal tissue-specific differentiated cell types are successful in the treatment of a few specific haematological tumours. However, this approach has not been widely applied to solid tumours because their developmental origins are less well understood. Recent advances suggest that understanding tumour cell plasticity and how intrinsic factors (such as genetic noise and microenvironmental signals, including physical cues from the extracellular matrix) govern cell state switches will help in the development of clinically relevant differentiation therapies for solid cancers. PMID- 26156640 TI - Consumption Safety of Pastries, Confectioneries, and Potato Products as Related to Fat Content. AB - STUDY AIM: To determine the content of the main groups of fatty acids in pastries, confectionery, and potato products, paying special attention to trans fatty acids and the products of fat oxidation and hydrolysis, as factors affecting the safety of consumption. METHODS: A total of 157 products were collected in Poland in 2009-2010. In fats extracted from samples, products of oxidation and hydrolysis were assayed using peroxide (PV), anisidine (AnV), and acid (AV) values. The fatty acid (FA) composition, especially the trans FAs (TFAs) content, was determined by gas chromatography. When assessing the TFA intake, Household Budget Surveys were considered. RESULTS: Highest content of fat was found for wafers with filling and crisps (32.3% and 29.3%, respectively). In 4 out of 9 groups of pastry and confectionery products studied, the quality of fat was decreased due to an excessive oxidation, as evidenced by a substantial content of secondary products of fat oxidation. The extracted fat was rich in SFA (on average, 50 g SFA/100 g FA) except fries and mixes. A great diversity of TFA content in fat of the products was found (0.1-24.8 g TFA/100 g FA). Wafers were characterized by the highest average content of TFA in the group of pastries (1.94 g TFA/100 g of product). Products of natural origin supplied 0.496 g of TFA per day, and those of industrial origin supplied about 1.5 g. CONCLUSIONS: The average TFA consumption, about 2 g/day, does not seem to affect health. However, an excessive consumption of pastry and confectionery products may present a risk, due not only to TFA but also to a high consumption of toxic secondary oxidation lipid products. Moreover, because 75% of TFAs in the diet were isomers of industrial origin, their further limitation and monitoring of their level in food seems highly recommendable. PMID- 26156638 TI - Tumorigenesis: it takes a village. AB - Although it is widely accepted that most cancers exhibit some degree of intratumour heterogeneity, we are far from understanding the dynamics that operate among subpopulations within tumours. There is growing evidence that cancer cells behave as communities, and increasing attention is now being directed towards the cooperative behaviour of subclones that can influence disease progression. As expected, these interactions can add a greater layer of complexity to therapeutic interventions in heterogeneous tumours, often leading to a poor prognosis. In this Review, we highlight studies that demonstrate such interactions in cancer and postulate ways to overcome them with better-designed therapeutic strategies. PMID- 26156641 TI - A Trypsin Inhibitor from Clitoria fairchildiana Cotyledons is Active Against Digestive Enzymes of Aedes aegypti Larvae. AB - Aedes aegypti, the principal mosquito vector of yellow fever, dengue fever and chikungunya fever virus-transmitted diseases, is an insect closely associated with humans and their housing habitats. As there is no commercially available vaccine, prevention is the most suggested form of avoiding disease spreading and a number of studies are being developed in order to give support to vector control operations. The present study reports on the identification of a trypsin inhibitor isolated from cotyledons of the Clitoria fairchildiana amazonic tree seeds, which was able to reduce by 87.93 % the activity of digestive enzymes of fourth instar A. aegypti larva. A partial amino acid sequence showed strong similarity with sequences from several trypsin inhibitors already reported in the literature. The 13,000 Da isolated inhibitor was seen to be active solely against trypsin-like enzymes, neither acting on papain, alpha-amylase nor on other serine proteases, such as elastase, chymotrypsin or subtilisin. At least six from seven active digestive proteases from A. aegypti larvae, visualized by zymography, were severely affected soon after exposed to the inhibitor. The strong and specific action of the isolated inhibitor against trypsin digestive enzymes of this insect vector led us to believe that this protein may be a good candidate for a prospective alternative biocontrol method. PMID- 26156642 TI - Mycobacterium tuberculosis Rv1265 promotes mycobacterial intracellular survival and alters cytokine profile of the infected macrophage. AB - Mycobacterium tuberculosis cAMP and underlying regulatory network are crucial for its survival and thrive in the presence of numerous stresses mounted by the host. Our studies mainly focus on the cAMP-induced M. tuberculosis gene Rv1265, which was shown to be up-regulated under hypoxia and during macrophage infection by addition of exogenous cAMP. To explore the role of Rv1265 in host-pathogen interactions, Rv1265 was expressed in a non-pathogenic Mycobacterium smegmatis. We found that Rv1265 was associated with cell envelope and can up-regulate some cell wall fatty acid components, especially the C26:0. The survival of the recombinant Ms_Rv1265 was enhanced within macrophages and under stress conditions such as low pH and SDS. Macrophages infected with Ms_Rv1265 increased transcription of pro-inflammatory cytokines IL-1beta, IL-6, and IL-12 P40 and anti-inflammatory cytokine IL-10 possibly through activation of NF-kappaB and ERK1/2 pathway. Our findings indicate that Rv1265 can enhance mycobacterial survival within macrophages, and perturb the cytokine profile of macrophage. PMID- 26156643 TI - Current-induced Orbital and Spin Magnetizations in Crystals with Helical Structure. AB - We theoretically show that in a crystal with a helical lattice structure, orbital and spin magnetizations along a helical axis are induced by an electric current along the helical axis. We propose a simple tight-binding model for calculations, and the results can be generalized to any helical crystals. The induced magnetizations are opposite for right-handed and left-handed helices. The current induced spin magnetization along the helical axis comes from a radial spin texture on the Fermi surface. This is in sharp contrast to Rashba systems where the induced spin magnetization is perpendicular to the applied current. PMID- 26156645 TI - The power of comparison. PMID- 26156644 TI - A comparison of auditory brainstem responses across diving bird species. AB - There is little biological data available for diving birds because many live in hard-to-study, remote habitats. Only one species of diving bird, the black-footed penguin (Spheniscus demersus), has been studied in respect to auditory capabilities (Wever et al., Proc Natl Acad Sci USA 63:676-680, 1969). We, therefore, measured in-air auditory threshold in ten species of diving birds, using the auditory brainstem response (ABR). The average audiogram obtained for each species followed the U-shape typical of birds and many other animals. All species tested shared a common region of the greatest sensitivity, from 1000 to 3000 Hz, although audiograms differed significantly across species. Thresholds of all duck species tested were more similar to each other than to the two non-duck species tested. The red-throated loon (Gavia stellata) and northern gannet (Morus bassanus) exhibited the highest thresholds while the lowest thresholds belonged to the duck species, specifically the lesser scaup (Aythya affinis) and ruddy duck (Oxyura jamaicensis). Vocalization parameters were also measured for each species, and showed that with the exception of the common eider (Somateria mollisima), the peak frequency, i.e., frequency at the greatest intensity, of all species' vocalizations measured here fell between 1000 and 3000 Hz, matching the bandwidth of the most sensitive hearing range. PMID- 26156646 TI - A Team Effort: Working With Non-Dermatologists to Deliver Better Patient Care. PMID- 26156647 TI - Oral Squamous Cell Carcinoma Mimicking Cervico-Facial Actinomycosis: A Rare Presentation and Review of Literature. PMID- 26156648 TI - Verrucous Carcinoma on the Dorsal Aspect of the Hand. PMID- 26156649 TI - Deleterious Effect of Radiation Therapy on Epidermodysplasia Verruciformis Patients. AB - BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by specific human papillomavirus (HPV) types associated with the development of multiple squamous cell carcinomas (SCC). The treatment for this skin tumour may be difficult. Among the therapy options, radiotherapy (RT) should be avoided due to its deleterious effects on HPV-induced carcinogenesis. OBJECTIVE: To describe 4 patients with EV who underwent radiotherapy to treat cutaneous SCC. METHODS: This is a retrospective study. The evolution of cutaneous SCC after adjuvant radiotherapy in 4 patients with EV was observed. RESULTS: This study included 4 patients with diagnosis of EV. All 4 of the patients had cutaneous SCC. They underwent surgical resection and adjuvant radiotherapy. Over a period of up to 2 years, there was aggressive tumour recurrence. CONCLUSION: Radiotherapy might be associated with progression of SCC in patients with EV, and it is recommended that radiotherapy should be avoided in this patient population. PMID- 26156650 TI - The role of computerised tomography in predicting visual outcome in ocular trauma patients. PMID- 26156652 TI - High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. AB - BACKGROUND: Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer. METHODS: Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions to tumour, 50 Gy in 30 fractions to elective lymph node volumes, 5 Gy endorectal brachytherapy boost, and oral tegafur-uracil 300 mg/m(2)) every weekday for 6 weeks. Endoscopies and biopsies of the tumour were done at baseline, throughout the course of treatment (weeks 2, 4, and 6), and 6 weeks after the end of treatment. We allocated patients with complete clinical tumour regression, negative tumour site biopsies, and no nodal or distant metastases on CT and MRI 6 weeks after treatment to the observation group (watchful waiting). We referred all other patients to standard surgery. Patients under observation were followed up closely with endoscopies and selected-site biopsies, with surgical resection given for local recurrence. The primary endpoint was local tumour recurrence 1 year after allocation to the observation group. This study is registered with ClinicalTrials.gov, number NCT00952926. Enrolment is closed, but follow-up continues for secondary endpoints. FINDINGS: Between Oct 20, 2009, and Dec 23, 2013, we enrolled 55 patients. Patients were recruited from three surgical units throughout Denmark and treated in one tertiary cancer centre (Vejle Hospital, Vejle, Denmark). Of 51 patients who were eligible, 40 had clinical complete response and were allocated to observation. Median follow-up for local recurrence in the observation group was 23.9 months (IQR 15.3-31.0). Local recurrence in the observation group at 1 year was 15.5% (95% CI 3.3-26.3). The most common acute grade 3 adverse event during treatment was diarrhoea, which affected four (8%) of 51 patients. Sphincter function in the observation group was excellent, with 18 (72%) of 25 patients at 1 year and 11 (69%) of 16 patients at 2 years reporting no faecal incontinence at all and a median Jorge-Wexner score of 0 (IQR 0-0) at all timepoints. The most common late toxicity was bleeding from the rectal mucosa; grade 3 bleeding was reported in two (7%) in 30 patients at 1 year and one (6%) of 17 patients at 2 years. There were no unexpected serious adverse reactions or treatment-related deaths. INTERPRETATION: High-dose chemoradiotherapy and watchful waiting might be a safe alternative to abdominoperineal resection for patients with distal rectal cancer. FUNDING: CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology and The Danish Council for Strategic Research. PMID- 26156653 TI - Is it time for watchful waiting for rectal cancer? PMID- 26156654 TI - EGFR tyrosine kinase inhibitors in squamous cell lung cancer. PMID- 26156655 TI - A Cost Analysis of Preoperative Breast MRI Use for Patients with Invasive Lobular Cancer. AB - BACKGROUND: Whereas the impact of magnetic resonance imaging (MRI) of the breast on the surgical management of breast cancer patients is well documented, less is known about its effect on health care costs. This study aimed to evaluate whether MRI use for women with invasive lobular carcinoma (ILC) significantly changes the cost of care. METHODS: Patients with ILC were recruited to a prospective registry study of breast MRI. Women who met the same inclusion criteria but had not undergone breast MRI were retrospectively identified for comparison. A micro costing analysis using institutional billing records was conducted. Nonparametric bootstrapping was used to compare the unadjusted cost differences between the patients receiving MRI and those receiving no MRI. RESULTS: Of the patients in this study, 51 had preoperative MRI, and 60 did not. Method of diagnostic biopsy, disease stage, oncologic procedure, and rates of contralateral prophylactic mastectomy were similar between the two groups. The patients in the MRI group were younger (median age 55 vs. 64 years; p = 0.01) and more likely to undergo reconstruction (45.1 vs. 25 %; p = 0.03). The median costs of care were significantly higher in the MRI group ($24,781 vs. $18,921; p < 0.01). After adjustment for clinical factors, MRI remained significantly associated with increased cost (p = 0.03). Other factors associated with increased cost included type of oncologic procedure (mastectomy vs. lumpectomy; p < 0.01), number of operations required to achieve negative margins (1 vs. >1; p < 0.01), and use of reconstruction (p < 0.01). CONCLUSION: Preoperative breast MRI increases the median total cost of care per patient. However, the contribution to the overall cost of care is modest compared with the cost of other interventions. PMID- 26156657 TI - Improving Sentinel Lymph Node Detection in Patients with Cervical Cancer. PMID- 26156651 TI - Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. AB - BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov, NCT01523587. FINDINGS: 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6.7 months (IQR 3.1-10.2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2.4 months [95% CI 1.9-2.9] vs 1.9 months [1.9-2.2]; hazard ratio [HR] 0.82 [95% CI 0.68-1.00], p=0.0427). At the time of the primary analysis of overall survival (median follow-up 18.4 months [IQR 13.8-22.4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7.9 months [95% CI 7.2-8.7] vs 6.8 months [5.9-7.8]; HR 0.81 [95% CI 0.69-0.95], p=0.0077), as were progression-free survival (median 2.6 months [95% CI 2.0-2.9] vs 1.9 months [1.9-2.1]; HR 0.81 [95% CI 0.69-0.96], p=0.0103) and disease control (201 [51%] of 398 patients vs 157 [40%] of 397; p=0.0020). The proportion of patients with an objective response did not differ significantly between groups (22 [6%] vs 11 [3%]; p=0.0551). Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib (39 [10%] vs nine [2%]), of grade 3 stomatitis with afatinib (16 [4%] vs none), and of grade 3 rash or acne with erlotinib (23 [6%] vs 41 [10%]). INTERPRETATION: The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim. PMID- 26156656 TI - The Prognostic Value of Signet-Ring Cell Histology in Resected Gastric Adenocarcinoma. AB - BACKGROUND: Conflicting data exist on the prognostic implication of signet-ring cell (SRC) histology in gastric adenocarcinoma (GAC). METHODS: All patients who underwent curative-intent resection of GAC from the seven institutions of the U.S. Gastric Cancer Collaborative between 2000 and 2012 were included. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Stage specific analyses were performed. RESULTS: A total of 768 patients met the inclusion criteria. SRC was present in 40.6 % of patients and was associated with female sex (52.9 vs. 38.6 %; p < 0.001), younger age (61 vs. 67 years; p < 0.001), poor differentiation (94.8 vs. 50.3 %; p < 0.001), perineural invasion (PNI) (41.4 vs. 23 %; p < 0.001), microscopically positive resection margins (R1, 24.7 vs. 8.6 %; p < 0.001), distal location (82.2 vs. 70.1 %; p < 0.001), receipt of adjuvant therapy (63 vs. 51.2 %; p = 0.002), and more advanced stage (stage 3: 55.2 vs. 36.5 %; p < 0.001). SRC was associated with earlier recurrence (56.7 months vs. median not reached; p = 0.009) and decreased OS (33.7 vs. 46.6 months; p = 0.011). When accounting for other adverse pathologic features, PNI (hazard ratio [HR] 1.57; p = 0.016) and higher stage (HR 2.64; p < 0.001) were associated with decreased RFS, but SRC was not. Although PNI (HR 1.52; p = 0.007), higher stage (HR 2.11; p < 0.001), greater size (HR 1.05; p = 0.016), and adjuvant therapy (HR 0.50; p < 0.001) were associated with OS, SRC was not. Similarly, when accounting for adverse pathologic factors on multivariate analysis, stage specific analyses showed no association between SRC and RFS or OS. CONCLUSIONS: SRC histology is associated with adverse pathologic features including poor differentiation, higher stage, and microscopically positive resection margins but is not independently associated with reduced RFS or OS. Identification of signet ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy. PMID- 26156658 TI - In vivo efficacy and molecular docking of designed peptide that exhibits potent antipneumococcal activity and synergises in combination with penicillin. AB - We have previously designed a series of antimicrobial peptides (AMPs) and in the current study, the in vivo therapeutic efficacy and toxicity were investigated. Among all the peptides, DM3 conferred protection to a substantial proportion of the lethally infected mice caused by a strain of penicillin-resistant Streptococcus pneumoniae. Synergism was reported and therapeutic efficacy was significantly enhanced when DM3 was formulated in combination with penicillin (PEN). No toxicity was observed in mice receiving these treatments. The in silico molecular docking study results showed that, DM3 has a strong affinity towards three protein targets; autolysin and pneumococcal surface protein A (pspA). Thus AMPs could serve as supporting therapeutics in combination with conventional antibiotics to enhance treatment outcome. PMID- 26156659 TI - [Bone substitutes used for sinus lift]. AB - In dental surgery today a variety of bone substitutes are used for sinus lift. After the increased application of synthetics during the last decade there has now been a move back to autologous bone transplants, combined with allogenic and xenogenic augmentation materials. The effects of transforming growth factors and recombinant equivalents of bone morphogenetic proteins remain to be seen. Covering the augmented area with a collagen membrane is the basic standard in many cases. Concomitant illnesses of dental origin or of the maxillary sinus have to be assessed prior to any sinus lift. Once complications such as laceration of the Schneiderian membrane, infection or adverse reaction have occurred, early and consistent therapy is required. PMID- 26156660 TI - Synthesis and biological evaluation of hybrid acridine-HSP90 ligand conjugates as telomerase inhibitors. AB - The synthesis and biological evaluation of a series of bifunctional acridine HSP90 inhibitor ligands as telomerase inhibitors is herein described. Four hybrid acridine-HSP90 inhibitor conjugates were prepared using a click-chemistry approach, and subsequently shown to display comparable results to the established telomerase inhibitor BRACO-19 in the TRAP-LIG telomerase assay. The conjugates also demonstrated significant cyctotoxity against a number of cancer cell lines, in the sub-MUM range. PMID- 26156661 TI - Efficacy and safety profile of anti-interleukin-1 treatment in Behcet's disease: a multicenter retrospective study. AB - Growing data have provided encouraging results on the use of interleukin (IL)-1 inhibitors in Behcet's disease (BD). This study was aimed at reporting the largest experience with anti-IL-1 agents in BD patients. We evaluated 30 BD patients receiving treatment with anti-IL-1 agents. The primary aims of the study were to evaluate the efficacy of anakinra (ANA) and canakinumab (CAN) in a cohort of BD. The secondary aims were to evaluate the overall safety profile of the treatments, explore the timing of response to therapy and any adjustment of dosage and frequency of drugs studied, and investigate predictive factors of response to therapy. The frequency of first line therapy was 90 % with ANA and 10 % with CAN. The overall number of subjects in complete remission after 12 months of therapy with anti-IL-1 drugs was 13: 6 maintained the initial therapy regimen, 1 maintained the same initial anti-IL-1 drug with further therapeutic adjustments, and the remaining 6 shifted from ANA to CAN. Among them, 3 used CAN for at least 12 months without therapeutic adjustments, 1 had therapeutic adjustments, and 3 had an overall history of a 12-month complete remission. Adverse events (AEs) were reported in 15 % patients who received ANA, represented in all cases by local cutaneous reactions, while no AE were observed in patients who received CAN; we did not observe any serious AEs (SAEs) during the follow-up period. Our data have confirmed that the use of anti-IL-1beta drugs is efficacious and safe with an overall acceptable retention on treatment. PMID- 26156663 TI - On-surface synthesis of carbon-based scaffolds and nanomaterials using terminal alkynes. AB - The covalent linking of acetylene compounds is an important synthetic tool to control carbon-carbon bond formation and has been extensively studied for more than a century. Notably, Glaser coupling and subsequently developed refined procedures present an important route for the fabrication of distinct carbon based scaffolds incorporating units with both sp(2)- and sp-hybridizations, such as carbyne chains, or two-dimensional (2D) graphyne or graphdiyne networks. However, the realization of the envisioned regular low-dimensional compounds and nanoarchitectures poses formidable challenges when following conventional synthesis protocols in solution, which we briefly overview. Now, recent developments in on-surface synthesis establish novel means for the construction of tailored covalent nanostructures under ultrahigh vacuum conditions. Here we focus on the exploration of pathways utilizing interfacial synthesis with terminal alkynes toward the atomically precise fabrication of low-dimensional carbon-rich scaffolds and nanomaterials. We review direct, molecular-level investigations, mainly relying on scanning probe microscopy, providing atomistic insights into thermally activated reaction schemes, their special pathways and products. Using custom-made molecular units, the employed homocoupling, cyclotrimerization, cycloaddition, and radical cyclization processes indeed yield distinct compounds, extended oligomers or 2D networks. Detailed insights into surface interactions such as bonding sites or conformational adaptation, and specific reaction mechanisms, including hierarchic pathways, were gained by sophisticated density functional theory calculations, complemented by X-ray spectroscopy measurements. For the fabrication of regular nanostructures and architectures, it is moreover imperative to cope with spurious side reactions, frequently resulting in chemical diversity. Accordingly, we highlight measures for increasing chemo- and regioselectivity by smart precursor design, substrate templating, and external stimuli. The ensuing preorganization of functional groups and control of side reactions increases product yields markedly. Finally, the electronic band structures of selected cases of novel low-dimensional hydrocarbon materials accessible with the monomers employed to date are discussed with a specific focus on their differences to theoretically established graphyne- and graphdiyne-related scaffolds. The presented methodology and gained insights herald further advancements in the field, heading toward novel molecular compounds, low-dimensional nanostructures, and coherently reticulated polymeric layers, eventually presenting well-defined arrangements with specific carbon carbon bond sequencing and electronic characteristics. The functional properties of these or other foreseeable scaffolds and architectures bear significant prospects for a wide range of applications, for example, in nanoelectronics, photonics, or carbon-based technologies. PMID- 26156664 TI - Multispectral Imaging of Pancreatic Mixed Acinar-neuroendocrine-ductal Carcinoma with Triple-immunoenzyme Staining. PMID- 26156665 TI - Indwelling Drains Are Not Necessary for Patients Undergoing One-level Anterior Cervical Fixation Surgery. AB - BACKGROUND: Anterior cervical discectomy and fusion (ACDF) has become a common procedure for cervical spine surgeries, since it is safe and effective in most patients. However, some patients develop life-threatening problems such as respiratory obstruction arising from rare postoperative hematoma and edema, although intraoperative bleeding caused by the connective tissue splitting procedure or bleeding caused by postoperative insertion of a suction tube has rarely been reported. Investigation of the requirement for indwelling drains in patients who undergo cervical spine surgery is necessary because of the pain, anxiety, and discomfort caused despite the use of high-quality materials. METHODS: Enrolled in the study were 43 patients who underwent one-level anterior cervical fixation surgery, including 23 (randomly selected) who received an indwelling drain (group A, mean age: 57.78+/-14.46 years, range: 39-82 years, male/female: 13/10), and 20 who received no indwelling drain (group B, mean age: 57.00+/-13.99 years, range: 29-81 years, male/female: 12/8). Intraoperative bleeding amounts, lateral views of plain cervical spine radiographs, prevertebral space (PVS) changes on plain radiographs and computed tomography (CT) images, wound inspections, and pain assessments on the Numeric Rating Scale (NRS) were compared between groups. In addition, a history of risk factors for bleeding, such as hypertension, diabetes, and cerebrovascular diseases which require antiplatelet therapy, was determined. Hepatic failure was observed in none of the patients. RESULTS: Postoperative CT images obtained the day following surgery showed no densities indicating the presence of postoperative hematoma in any of the 43 patients. The maximum amount of intraoperative bleeding was 10 mL, with no significant difference between groups. No patients reported an obvious pain level on NRS, but the pain was significantly milder in group B (A: 1.326+/-0.911, B: 0.555+/-0.556, p=0.0037). The postoperative PVS increment on plain radiographs was comparable between groups (A: 1.778+/-0.992, B: 1.730+/-0.966, p=0.8728). DISCUSSION: Given the negligible intraoperative and postoperative bleeding observed in both groups, and the lack of difference in PVS increments between the groups, our results suggested that indwelling drains are not required for patients undergoing typical anterior cervical fixation surgery. However, it is important to take care of major vessels such as the superior and inferior thyroid arteries and the external jugular vein as well as the prevertebral venous plexus during surgery. PMID- 26156662 TI - Future Treatment of Hypertension: Shifting the Focus from Blood Pressure Lowering to Arterial Stiffness Modulation? AB - Isolated systolic hypertension is the commonest form of hypertension from middle age onwards. Achieving target systolic blood pressure (BP) control remains difficult in everyday clinical practice and even under clinical trial conditions. Most antihypertensive medicines were designed to lower peripheral vascular resistance, which was considered the haemodynamic determinant of hypertension; most are effective in reducing steady but not pulsatile components of BP. Arterial stiffness, defined via aortic length-specific pulse wave velocity (PWV), is thought to be an important determinant of pulse pressure widening through its effects on the timing and amplitude of pressure wave reflection, and/or the aorta's Windkessel function, or its excess 'reservoir' pressure. Whereas pulse pressure is neither an independent nor consistent cardiovascular risk factor, particularly below the age of about 60 years, PWV has become the most powerful predictor of cardiovascular outcomes including mortality, independent of systolic, pulse, mean or other BP components. PWV is therefore a more direct target for treatment. This review addresses the potential therapeutic options for targeting arterial stiffness and the role of pulse pressure. PMID- 26156666 TI - Three-dimensional Analysis of the Attachment and Path of the Transverse Carpal Ligament. AB - PURPOSE: The purpose of this study was to describe and evaluate the detailed anatomic locations and areas of ligamentous attachments and paths of the transverse carpal ligament (TCL) on a three-dimensional (3-D) surface model. METHODS: Ten fresh-frozen cadaver wrists were used to dissect and identify the TCL. Their ligament attachments and whole bone surfaces were digitized three dimensionally and their areas evaluated. The attachments of each ligament were represented in a model combining CT surfaces overlaid by a digitized 3-D surface, and were also visually depicted with a different color for each on 3-D images of the bones. RESULTS: The TCL was found to be composed of two or three discrete ligaments. Both the trapezium-hook of hamate ligament and the trapezium-pisiform ligament were identified in all ten specimens. The scaphoid-pisiform ligament was found in only two of the ten specimens. The average areas of the attachments of the TCL were 42.7 mm(2) on the trapezium, 30.0 mm(2) on the hook of hamate, 21.6 mm(2) on the pisiform, and 12.7 mm(2) on the scaphoid. CONCLUSIONS: The anatomic 3-D attachment sites of the TCL were visually shown qualitatively, and their areas quantified. This 3-D information offers further knowledge and understanding of the anatomy and biomechanics of the TCL. It could also help in the accurate assessment of radiographic images and treatment of various wrist injuries and diseases when performing such procedures as carpal tunnel release, Guyon's canal release, trapeziectomy, hook of hamate excision, or arthroscopy. PMID- 26156667 TI - Detection and Evaluation of Pulmonary Hypertension by a Synthesized Right-Sided Chest Electrocardiogram. AB - BACKGROUND: Current standard 12-lead electrocardiogram (ECG) criteria for diagnosing pulmonary hypertension (PH) have a low sensitivity. Although the right sided chest ECG (V3R-V5R) increases the diagnostic accuracy, these additional leads are not routinely recorded. The aim of the present study was to assess the usefulness of the synthesized right-sided chest ECG (Syn-ECG), generated from 12 lead ECG information, in the detection and evaluation of PH. PATIENTS AND METHODS: The Syn-ECG waveforms in 30 patients with PH, defined as an estimated pulmonary arterial systolic pressure (PASP) >35 mmHg, were compared to those in 30 age- and gender-matched normal subjects. RESULTS: The R wave amplitude and R/S ratio in the Syn-ECGs were significantly (P<0.01) greater in patients with PH than in the controls. The R wave amplitude in the Syn-ECGs exhibited a significant and better correlation (correlation coefficient 0.513-0.596, P<0.001) with the PASP than lead V1 (correlation coefficient 0.375, P=0.02). A receiver operating characteristic curve analysis showed that the R wave amplitude (AUC 0.802, P<0.001) and R/S ratio (AUC 0.823, P<0.001) in the synthesized V5R was a good predictor of PH. New criteria, including 1) an R in V5R>0.12 mV, and 2) R/S ratio in V5R>0.42, had an improved sensitivity (0.63 and 0.73, respectively) and comparable specificity (0.93 and 0.87, respectively) to the conventional criteria (sensitivity 0.10-0.43, specificity 0.90-1.00). CONCLUSION: The diagnostic criteria derived from the Syn-ECG provided better diagnostic accuracy than the known conventional criteria from the standard 12-lead ECG. This technique described in the present study may be useful for diagnosing and evaluating PH. PMID- 26156668 TI - Sellar Chondroma with Endocrine Dysfunction that Resolved after Surgery: Case Report. AB - Chondromas originating from the sella turcica are rare, and the most common initial symptoms are headache and visual disturbance. We describe a case of sellar chondroma with endocrine impairment as an initial manifestation that completely resolved after surgery. A 40-year-old Japanese woman with amenorrhea and galactorrhea for the last 2 years was referred to our department of neurosurgery for the evaluation of high prolactin levels and a tumor in the sella turcica. A biochemical assessment indicated endocrine dysfunction. Magnetic resonance imaging and computed tomography indicated a tumor in the sella turcica. The patient's presentation favored the preoperative diagnosis of pituitary adenoma or Rathke's cleft cyst. However, because calcification was detected, other types of tumors, such as craniopharyngioma, meningioma, and chordoma, were also considered. Endoscopic transsphenoidal surgery was performed, and the possibility of a bony tumor was recognized. Finally, the tumor was completely removed, and the histopathological findings confirmed chondroma. The postoperative course was uneventful, and endocrine function improved. Five years after surgery, the patient is doing well without pituitary insufficiency, pituitary hormone medications, or signs of tumor recurrence. In cases of sellar chondroma, endocrine dysfunction sometimes precedes other symptoms, such as headache and visual disturbance. When examining a patient with an intrasellar tumor harboring calcification, clinicians must consider the possibility of sellar chondroma. Furthermore, to the best of our knowledge, this case is the first of sellar chondroma treated with endoscopic surgery to be reported. PMID- 26156669 TI - Hobnail Hemangioma: A Case Report. AB - Hobnail hemangioma is a small, solitary, benign vascular tumor that shows a biphasic histological pattern of dilated vascular spaces in the superficial dermis and narrow vascular structures in the deeper dermis. In the superficial dermis, dilated, irregular, thin-walled vascular spaces are lined by plump endothelial cells with large nuclei which protrude into the lumina like hobnails. A 43-year-old Japanese man presented with an 11*8-mm bluish-red macule surrounding a 6*3-mm violaceous, slightly elevated papule of the lumbar region of 6 months' duration. Total resection was performed under local anesthesia. Microscopic examination revealed a biphasic pattern with dilated superficial vessels whose endothelial cells were plump with intraluminal papillary projections, showing a "hobnail" appearance, in the papillary layer and upper dermis, and vascular spaces forming slitlike spaces, some of them dissecting collagen fibers, in the deeper dermis. Neither true atypia nor mitotic figures were present. The findings were consistent with those of hobnail hemangioma. Immunohistochemical analysis of the endothelia of the superficial vessels showed that CD31 and D2-40 were expressed, factor VIII was focally expressed, and CD34 and alpha-SMA were not expressed. In the endothelia of the deeper vessels, CD31, CD34, factor VIII, and alpha-SMA were expressed, but D2-40 was not expressed. These findings suggest that hobnail hemangioma also shows a biphasic immunohistochemical pattern because of its origin from both lymphatic vessels and blood vessels. PMID- 26156670 TI - Placenta with Old, Diffuse Infarction that Was Difficult to Differentiate from a Placental Tumor. AB - Placental lesions, including placental infarction, are associated with fetal and neonatal mortality and morbidity. We present a case of fetal growth restriction associated with an old, diffuse placental infarction. Because the placenta had only a single viable cotyledon, the others being atrophic, the lesion appeared to be a placental tumor on prenatal ultrasonography. The patient did not have pregnancy-induced hypertension. At 31 weeks of gestation, a cesarean delivery was performed because of fetal growth arrest and breech presentation. A small-for gestational age infant was delivered with Apgar scores of 8 at both 1 and 5 minutes, and the infant had cleft palate and cleft lips. Pathological examination of the placenta revealed an old, diffuse infarction without neoplastic change. In cases in which a placental tumor causing fetal growth restriction is strongly suspected, diffuse placental infarction should be considered as part of the differential diagnosis, because placental tumors are associated with poor maternal prognosis. PMID- 26156671 TI - Pulmonary Nocardiosis due to Nocardia asiatica in an Immunocompetent Host. AB - We describe a case of pulmonary nocardiosis due to Nocardia asiatica in an immunocompent 64-year-old-female. Wadowsky-Yee-Okuda-alpha-ketoglutarate (WYOalpha) agar, a selective media for Legionella species, was useful for the detection based on the growth-inhibition of normal oral flora and growth promotion of Nocardia species. PMID- 26156672 TI - Habitual Alcohol Consumption during Pregnancy and Perinatal Outcomes. AB - We investigated perinatal outcomes in pregnant Japanese women who habitually consumed alcohol during pregnancies managed at our hospital. Of the 4,791 Japanese women with singleton deliveries at >=22 weeks' gestation, 44 (0.9%) were found to have habitually consumed alcohol during pregnancy. Multiple logistic regression analyses suggested that habitual alcohol consumption during pregnancy was not associated with adverse perinatal outcomes. However, 64% of the women who habitually consumed alcohol during pregnancy also habitually smoked; smoking leads to increased risks of a low birth weight and placental abruption. PMID- 26156673 TI - Evolution of magnetization due to asymmetric dimerization: theoretical considerations and application to aberrant oligomers formed by apoSOD1(2SH). AB - A set of coupled differential equations is presented describing the evolution of magnetization due to an exchange reaction whereby a pair of identical monomers form an asymmetric dimer. In their most general form the equations describe a three-site exchange process that reduces to two-site exchange under certain limiting conditions that are discussed. An application to the study of sparsely populated, transiently formed sets of aberrant dimers, symmetric and asymmetric, of superoxide dismutase is presented. Fits of concentration dependent CPMG relaxation dispersion profiles provide measures of the dimer dissociation constants and both on- and off-rates. Dissociation constants on the order of 70 mM are extracted from fits of the data, with dimeric populations of ~2% and lifetimes of ~6 and ~2 ms for the symmetric and asymmetric complexes, respectively. This work emphasizes the important role that NMR relaxation experiments can play in characterizing very weak molecular complexes that remain invisible to most biophysical approaches. PMID- 26156674 TI - Periodontal Inflammatory Burden and Salivary Matrix Metalloproteinase-8 Concentration Among Patients With Chronic Kidney Disease at the Predialysis Stage. AB - BACKGROUND: The aim of the present study is to compare periodontal inflammatory burden related to the salivary matrix metalloproteinase (MMP)-8 concentration among patients with chronic kidney disease (CKD) at the predialysis stage. METHODS: Salivary samples from 118 predialysis patients were assayed for MMP-8 by immunofluorometric assay. Of the patients, 43 (36%) had diabetic nephropathy, whereas 75 (64%) had other kidney disease. Clinical and radiographic oral health examination was made at Helsinki University Hospital. Oral and general health data including laboratory findings were recorded from hospital records, and the periodontal inflammatory burden index (PIBI) and the total dental index (TDI) were calculated. Results were analyzed with cross tabulation, Pearson chi(2) test, and Mann-Whitney U test. RESULTS: Results included elevated PIBI, increased TDI, and two or more sites with >= 6 mm or deeper periodontal pocket, associated with elevated salivary MMP-8 concentrations (P < 0.05 in all associations). The diabetic nephropathy group and patients with high hemoglobin A1c (HbA1c) values (>= 6.5%, >= 48 mmol/mol) exerted slightly elevated median salivary MMP-8 values compared with the other CKD group or regarding patients with HbA1c values < 6.5%, but these differences were not statistically significant. CONCLUSIONS: Elevated salivary MMP-8 associated significantly with more severe oral/periodontal inflammatory burden among patients with CKD at the predialysis stage. Thus, salivary MMP-8 analysis could give adjunctive information regarding oral health. PMID- 26156675 TI - Chlorhexidine Uptake and Release From Modified Titanium Surfaces and Its Antimicrobial Activity. AB - BACKGROUND: Decontamination by adjunctive antiseptic agents such as chlorhexidine (CHX) is often recommended for the treatment of peri-implant infections. However, its action on the titanium implant surface needs further research. This study is designed to evaluate the ability of modified titanium surfaces to release chlorhexidine after periodic CHX exposure. METHODS: Four titanium surfaces were prepared: 1) no surface treatment control (machined surface [MA]); 2) an acid mix of 10% HNO3 and 5% HF (HNF); 3) resorbable blast media (RBM); and 4) sandblasting and acid etching (SLA). Each surface was analyzed using a confocal laser scanning microscope and a scanning electron microscope. Each sample was incubated with whole saliva or phosphate-buffered saline for 2 hours. Measurements of CHX release were performed using spectrometry on days 1, 2, and 5 after 1-minute exposure to 0.5% chlorhexidine digluconate solution during a 5-day cycle. CHX releasing experiments were repeated three consecutive times for 15 days. The antimicrobial activity of CHX-adsorbed disks was determined by a disk diffusion test using Streptococcus gordonii. RESULTS: The CHX-adsorbed titanium surfaces exhibited a short-term release of CHX, and CHX levels dropped rapidly within 3 days. SLA and RBM with smaller and narrower depressions released more CHX than HNF and MA, specifically in the saliva-coated group. The disk diffusion test revealed that after CHX uptake, saliva-coated SLA and RBM showed the highest antimicrobial activity. CONCLUSION: This study suggests that CHX release is significantly influenced by titanium surface modifications and that SLA and RBM might provide effective CHX uptake capacity in the saliva-filled oral cavity. PMID- 26156676 TI - Effect of Cone-Beam Computed Tomography Field of View and Acquisition Frame on the Detection of Chemically Simulated Peri-Implant Bone Loss In Vitro. AB - BACKGROUND: The aim of this study is to determine the influence of field of view (FOV) and number of acquisition projection images (frames) on the detection of chemically simulated peri-implant defects by cone-beam computed tomography (CBCT) using an in vitro bovine rib bone model. METHODS: Eighty implants were placed in bovine ribs in which small and large bone defects were created using 70% perchloric acid. CBCT images were acquired at three acquisition protocols: protocol 1 (FOV 4 * 4 cm, 0.08-mm voxel size, 1,009 frames [high fidelity]; protocol 2 (same as protocol 1 except 512 frames [standard]); and protocol 3 (FOV 14 * 5 cm, 0.25-mm voxel size; high fidelity). Two oral and maxillofacial radiologists (OMRs) and two oral and maxillofacial surgeons (OMSs) rated the presence or absence of bone defects on a five-point scale. kappa and area under the curve (AUC) were calculated and compared using analysis of variance with post hoc Tukey test at P <= 0.05. RESULTS: Intra- and interobserver agreement for OMRs ranged from moderate to good and from slight to moderate for OMSs. For the detection of small lesions, protocol 1 (AUC 0.813 +/- 0.045) provided higher detection rates than protocol 2 (AUC 0.703 +/- 0.02) and protocol 3 (AUC 0.773 +/ 0.55) [F(2,9) = 1.6377]. For larger defects, the trends were similar, with protocol 1 (AUC 0.852 +/- 0.108) providing higher detection rates than protocol 2 (AUC 0.730 +/- 0.045) and protocol 3 (AUC 0.783 +/- 0.058) [F(2,9) = 1.9576]. CONCLUSION: Within the limits of this study, optimal detection of chemically simulated pericircumferential implant crestal bone defects is achieved at the least radiation detriment using the smallest FOV, the highest number of acquisition frames, and the smallest voxel. PMID- 26156677 TI - NSC-640358 acts as RXRalpha ligand to promote TNFalpha-mediated apoptosis of cancer cell. AB - Retinoid X receptor alpha (RXRalpha) and its N-terminally truncated version tRXRalpha play important roles in tumorigenesis, while some RXRalpha ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRalpha and tRXRalpha. Here we describe NSC-640358 (N-6), a thiazolyl pyrazole derived compound, acts as a selective RXRalpha ligand to promote TNFalpha-mediated apoptosis of cancer cell. N-6 binds to RXRalpha and inhibits the transactivation of RXRalpha homodimer and RXRalpha/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRalpha, essential for 9-cis-retinoic acid binding and activating RXRalpha transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRalpha by forming extra pi-pi stacking interactions with N-6, indicating a distinct RXRalpha binding mode of N 6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRalpha-LBD by binding to the ligand binding pocket of RXRalpha-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRalpha. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor alpha (TNFalpha)-induced AKT activation and stimulates TNFalpha-mediated apoptosis in cancer cells in an RXRalpha/tRXRalpha dependent manner. The inhibition of TNFalpha-induced tRXRalpha/p85alpha complex formation by N-6 implies that N-6 targets tRXRalpha to inhibit TNFalpha-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRalpha ligand with a unique RXRalpha binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFalpha-mediated cancer cell apoptosis by targeting RXRalpha/tRXRalpha. PMID- 26156678 TI - Sexual Minority Stressors, Internalizing Symptoms, and Unhealthy Eating Behaviors in Sexual Minority Youth. AB - BACKGROUND: Sexual minorities are more likely than heterosexuals to engage in unhealthy eating behaviors. PURPOSE: The purpose of this study is to examine sexual minority stressors and internalizing symptoms as predictors of unhealthy eating behaviors among sexual minority youths. METHODS: We used longitudinal data from 1461 sexual minority youths in the Growing Up Today Study, across ages 14-28 years. We hypothesized that sexual minority stressors would predict unhealthy eating behaviors, in part due to internalizing symptoms. Linear regression models fit via generalized estimating equations were stratified by gender and sexual orientation. RESULTS: Significant positive and inverse associations between stressors and eating behaviors were detected among females and males, with more significant associations among females. Associations were attenuated by up to 71 % for females and 12 % for males when internalizing symptoms were added to the models. CONCLUSIONS: Sexual minority stressors predicted unhealthy eating behaviors overall and more so for some sexual orientation and gender groups; associations were partially explained by internalizing symptoms. The conceptual model appears to best describe the experiences of bisexual females. Findings have clinical implications for adolescent health. PMID- 26156679 TI - Is ABO mismatch another risk factor for allogeneic hematopoietic stem cell transplantation in pediatric thalassemic patients? AB - The ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic HSCT. Nevertheless, conflicting data still exist about the influence of ABO incompatibility on transplant outcome in pediatric patients with thalassemia. Fifty-one children with beta-thalassemia major who underwent allogeneic HSCT were enrolled this study. Twenty-three of them (45%) received an ABO-incompatible transplant [minor ABO mismatch: six (26%), major ABO mismatch: fourteen (61%), and bidirectional mismatch: three (13%)]. In this study, ABO incompatibility did not significantly impair GVHD, VOD, neutrophil and platelet engraftment, TRM, OS and TFS. Particularly in major and bidirectional ABO mismatched patients, a delayed erythroid recovery was recorded as compared to the group receiving an ABO-compatible graft (median time, 31 and 38 days vs. 19.5 days; p: 0.02 and p: 0.03). Median time to red cell transfusion independence was significantly longer in major ABO-incompatible patients (median time, 87 days vs. 32 days; p: 0.001). Therefore, whenever feasible, major ABO-mismatched donors should be avoided in HSCT recipients, to prevent delayed erythroid recovery with prolonged RBC transfusion needs and impaired quality of life. PMID- 26156680 TI - One year outcome of hemi-Descemet membrane endothelial keratoplasty. AB - PURPOSE: To evaluate the 1-year clinical outcome after semi-circular Descemet membrane endothelial keratoplasty (hemi-DMEK) in a first case series. METHODS: In three eyes of three patients with Fuchs endothelial dystrophy, best corrected visual acuity (BCVA), endothelial cell density (ECD), pachymetry, and intra- and postoperative complications were evaluated after transplantation of a semi circular ~12 mm diameter Descemet graft (hemi-DMEK graft). RESULTS: All corneas cleared within 6 months and showed a stable pachymetry thereafter (527, 535, and 490 MUm, respectively). Compared to preoperative measurements, average central ECDs dropped by 51 % (56, 39, and 59 %, respectively) at 3 months, 53 % (57, 38, and 63 %, respectively) at 6 months, and 59 % (60, 47, and 71 %, respectively) at 12 months. Denuded stromal areas adjacent to the hemi-DMEK graft cleared and at 12 months peripheral ECD counts ranged from 724 to 1051 cells/mm(2). At 12 months, BCVA was 20/22 (0.9), 20/40 (0.5, amblyopic eye) and 20/17 (1.2). No postoperative complications occurred throughout the study period. CONCLUSIONS: Hemi-DMEK may provide visual outcomes similar to those in standard DMEK at the 1 year postoperative mark. If also graft survival and complication rates prove to be similar, hemi-DMEK could become the next step in endothelial keratoplasty, owing to its potential to double the yield of transplants from the same donor pool (two hemi-DMEK grafts can be prepared from one donor cornea). PMID- 26156681 TI - Aesthetic assessment in periciliary "v-incision" versus conventional external dacryocystorhinostomy in Asians. AB - PURPOSE: To determine the functional and aesthetic outcomes of periciliary "v incision" external dacryocystorhinostomy (DCR) and to compare with conventional approach. METHOD: Charts review of consecutive cases of "v-incision" (VDCR) or conventional DCR performed in a single institute, between January 2007 and March 2014. All procedures were performed or supervised by a single surgeon. Two periciliary incisions were made near the skin-mucosal junction at the upper and lower eyelid margins medial to the punctum joining at the medial canthal angle to form a "v" shape. Subcutaneous dissection was carried out inferomedially to reach the anterior lacrimal crest. DCR was then performed in the usual manner. Functional success was defined as no persistent or recurrent epiphora and patency on irrigation of the lacrimal drainage system at least 6 months post-surgery. A cross-sectional aesthetic survey was conducted by asking the patients to rate their scar appearance satisfaction on a visual analogue scale (VAS). External photographs were graded by two independent, masked physicians using VAS as well as the Stony Brook scar evaluation scale (SBSES). RESULTS: Sixty-one patients with median age of 64 years met the inclusion criteria, with median follow-up duration of 28 months. Thirty-eight eyes underwent VDCR, and 23 had conventional DCR. The functional success rate for VDCR was 83.3, 95 % confidence intervals (95%CI) [lower 0.68, upper 0.92] and for conventional DCR was 73.9 %, 95%CI [lower 0.54, upper 0.87]; without statistically significant difference (p = 0.38). VDCR patients rated higher aesthetic outcome on VAS (mean scores 95.5 +/- 16.8 vs 82.9 +/- 25.1, p = 0.03). On the SBSES, both observers gave higher aesthetic scores to the VDCR group (observer #1 4.6 +/- 1.1 and #2 4.7 +/- 1.2, p < 0.01) than conventional DCR (observer #1 3.1 +/- 2.8 and #2 2.8 +/- 2.1, p < 0.01). More patients reported that they could wear spectacles within 1 week post VDCR (44.7 vs 4.3 %, p < 0.01). CONCLUSION: "V-incision" external DCR has a similar functional success rate to that of the conventional approach and has superior aesthetic outcomes as reported by surgeons and patients. However, a higher proportion of trainees under supervision performed conventional DCR, and it is uncertain whether the outcomes were also influenced by the level of surgeon's expertise. PMID- 26156682 TI - Venting incisions in DSAEK: implications for astigmatism, aberrations, visual acuity, and graft detachment. AB - PURPOSE: To evaluate the impact of venting incisions on the best corrected visual acuity (BCVA), astigmatism, aberrations, and risk of graft detachment in Descemet stripping automated keratoplasty (DSAEK). METHODS: This was a retrospective, comparative, consecutive case series of DSAEK procedures performed with (n = 266) and without (n = 110) venting incisions. Patients were treated with DSAEK for Fuchs' endothelial dystrophy at Aarhus University Hospital between 2011 and 2013. Data included preoperative keratometry and postoperative BCVA, subjective astigmatism, and Pentacam(r) HR tomography with corneal front surface (CFS) aberrations at 1 to 2 years of follow-up. Numbers of triple procedures (concurrent cataract surgery) and post-operative graft detachments were also noted. The venting and non-venting groups were compared by the data-means. Unpaired t-tests and Mann-Whitney tests were used for normally and non-normally distributed data, respectively. Differences in graft detachments were analyzed with Fisher's exact and Chi square test. RESULTS: There was no significant difference in any parameter, except the numbers of triple procedures. BCVA (logMAR) was 0.25 +/- 0.18 in the venting group and 0.25 +/- 0.19 in the non venting group (p = 0.92), subjective astigmatism was -1.53 +/- 0.99 diopters and 1.33 +/- 0.78 diopters (p = 0.15), respectively. CFS astigmatism and higher order aberrations were statistically uniform. The relative risk (RR) of graft detachment was also uniform between the venting versus non-venting group (RR 0.72, p = 0.40), and between triple versus non-triple procedures (RR 0.71, p = 0.43). The preoperative corneal curvature had no impact on the risk of graft detachment (p = 0.74). CONCLUSION: Venting incisions in DSAEK do not significantly alter BCVA, astigmatism, CFS aberrations or reduce the risk of graft detachment in triple or non-triple procedures. PMID- 26156683 TI - Trends in the disapproval and use of marijuana among adolescents and young adults in the United States: 2002-2013. AB - BACKGROUND: Despite policy changes related to the use and distribution of marijuana in cities and states across the country, few studies have examined changes in disapproval and use of marijuana among American youth. OBJECTIVES: To examine trends in disapproval and use of marijuana among adolescents and young adults in the United States. METHOD: We employed nationally representative data spanning the period of 2002-2013. Analyses were based on self-reported measurements from 105,903 younger adolescents (aged 12-14); 110,949 older adolescents (aged 15-17); and 221,976 young adults (aged 18-25). RESULTS: Between 2002 and 2013 the proportion of adolescents aged 12-14 reporting "strong disapproval" of marijuana use initiation increased significantly from 74.4-78.9%. Concurrently, a significant decrease in past 12-month marijuana use (OR = 0.98, 95% CI = 0.97-0.99) was observed among younger adolescents. No significant trend was observed for marijuana use disapproval among adolescents aged 15-17 between 2002 and 2013. Yet a significant (OR = 0.99, 95% CI = 0.98-0.99) decrease in the past 12-month marijuana use was observed (2002 = 26.2%, 2013 = 21.9%) among this group. Among young adults (aged 18-25), a substantial decrease - from 40.5% in 2002 to 22.6% in 2013 - was observed in the proportion reporting "strong disapproval" of marijuana use initiation; however, increases in the past 12-month use were relatively small among young adults (Delta = 2.21) but statistically significant (OR = 1.02, 95% = 1.01-1.02). CONCLUSIONS: Changes are underway in the perception and use of marijuana among American youth. However, changes differ in important ways among youth from distinct developmental subgroups. PMID- 26156684 TI - Bioinformatic analysis of specific genes in diabetic nephropathy. AB - OBJECTIVE: We attempt to explore the pathogenesis and specific genes with aberrant expression in diabetic nephropathy (DN). METHODS: The gene expression profile of GSE1009 was downloaded from Gene Expression Omnibus database, including 3 normal function glomeruli and DN glomeruli from cadaveric donor kidneys. The differentially expressed genes (DEGs) were analyzed and the aberrant gene-related functions were predicted by informatics methods. The protein-protein interaction (PPI) networks for DEGs were constructed and the functional sub network was screened. RESULTS: A total of 416 DEGs were found to be differentially expressed in DN samples comparing with normal controls, including 404 up-regulated genes and 12 down-regulated genes. DEGs were involved in the process of combination to saccharides and the decline of tissue repairing ability of the organisms. The genes of VEGFA, ACTG1, HSP90AA1 had high degree in the PPI network. The main biological process of genes in the sub-network was related with cell proliferation and signal transmitting of cell membrane receptor. CONCLUSION: Significant nodes in PPI network provide new insights to understand the mechanism of DN. VEGFA, ACTG1 and HSP90AA1 may be the potential targets in the DN treatment. PMID- 26156685 TI - Single nucleotide polymorphisms near IL28B gene and response to treatment of chronic hepatitis C in hemodialysis patients. AB - BACKGROUND: It has been shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene were associated with sustained virological response following standard antivirological treatment of chronic hepatitis C. OBJECTIVES: The aim of the study was to evaluate the association between SNPs near the IL28B gene and response to the treatment of chronic hepatitis C in hemodialysis patients. PATIENTS AND METHODS: The study group included 24 hemodialysis patients with chronic hepatitis C routinely treated with pegylated interferon alpha-2 a. HCV genotype 1 was the cause of chronic hepatitis C in all study participants. Sustained virological response was determined by an assay with a sensitivity of 20 IU/mL, 6 months after completion of the antivirological treatment. The genotyping of the three most widely studied IL28B gene polymorphisms (rs12979860, rs8099917, and rs12980275) was performed in all study participants. RESULTS: Sustained virological response was achieved in 50% of the treated patients. The treatment response was significantly associated with the CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275 (p = 0.003, p = 0.009, and p = 0.012, respectively). CONCLUSIONS: The three most widely studied SNPs near the IL28B gene were associated with sustained virological response following antivirological treatment of chronic hepatitis C in hemodialysis patients. PMID- 26156686 TI - Left ventricular remodeling and arterial remodeling in patients with chronic kidney disease stage 1-3. AB - INTRODUCTION: Chronic kidney disease (CKD) is an independent factor for cardiovascular system complications, such as arterial hypertension, left ventricular hypertrophy (LVH), heart failure or accelerated atherosclerosis progression. The aim of the paper was to analyze left ventricular and arterial remodeling in patients with CKD stages 1-3 to identify the subclinical marker of cardiovascular system damage which changes first in the course of CKD. METHODS: The examined group consisted of 90 patients with CKD stage 1-3 and 30 subjects constituting the control group. Left ventricular mass index (LVMI), left ventricular relative wall thickness (RWT) and ejection fraction (EF) were determined by echocardiographic examination. Pulse wave velocity (PWV) between the carotid and femoral arteries as well as common carotid artery intima-media thickness (IMT) was measured. 24-h ambulatory blood pressure monitoring was performed in all subjects. RESULTS: No differences were found between blood pressure values in the examined groups of patients with CKD1, CKD2 and CKD3. Concentric remodeling was found in 20.0%, concentric hypertrophy in 22.2% and eccentric hypertrophy in 18.9% of patients. LVMI values in patients with CKD2 and 3 were higher than in the control group. IMT values in patients with CKD3 were higher than in patients with CKD2. PWV in patients with stage 3 CKD was significantly higher than in the control group (p < 0.05). CONCLUSIONS: In the course of CKD, the left ventricle undergoes remodeling earlier than large arterial vessels. Echocardiographic assessment of LVH in early stages of CKD may identify patients at increased cardiovascular risk. PMID- 26156688 TI - Capacity planning and appointment scheduling for new patient oncology consults. AB - To ensure that patients receive timely access to care, it has become increasingly important to use existing care provider capacity as efficiently as possible and to make informed capacity planning decisions. To support this decision-making process at a regional cancer center in British Columbia (Canada), we undertook a simulation and optimization based study that investigated the simultaneous impact of the available number of new patient consultation slots, appointment scheduling policies and oncologist specialization configurations on the timeliness of patient access to care and physician workload. The key contribution of this paper is the methodological framework it provides to decision makers who manage specialty clinics to ensure that they are using their resources efficiently and making informed strategic short- and mid-term capacity planning decisions for new patient demand. PMID- 26156687 TI - Striatal and Pallidal Activation during Reward Modulated Movement Using a Translational Paradigm. AB - Human neuroimaging studies of reward processing typically involve tasks that engage decision-making processes in the dorsal striatum or focus upon the ventral striatum's response to feedback expectancy. These studies are often compared to the animal literature; however, some animal studies include both feedback and nonfeedback events that activate the dorsal striatum during feedback expectancy. Differences in task parameters, movement complexity, and motoric effort to attain rewards may partly explain ventral and dorsal striatal response differences across species. We, therefore, used a target capture task during functional neuroimaging that was inspired by a study of single cell modulation in the internal globus pallidus during reward-cued, rotational arm movements in nonhuman primates. In this functional magnetic resonance imaging study, participants used a fiberoptic joystick to make a rotational response to an instruction stimulus that indicated both a target location for a capture movement and whether or not the trial would end with feedback indicating either a small financial gain or a neutral outcome. Portions of the dorsal striatum and pallidum demonstrated greater neural activation to visual cues predicting potential gains relative to cues with no associated outcome. Furthermore, both striatal and pallidal regions displayed a greater response to financial gains relative to neutral outcomes. This reward-dependent modulation of dorsal striatal and pallidal activation in a target-capture task is consistent with findings from reward studies in animals, supporting the use of motorically complex tasks as translational paradigms to investigate the neural substrates of reward expectancy and outcome in humans. PMID- 26156692 TI - [The X-VeRT study]. PMID- 26156691 TI - Efficacy and safety of B-mode ultrasound-guided percutaneous transhepatic gallbladder drainage combined with laparoscopic cholecystectomy for acute cholecystitis in elderly and high-risk patients. AB - BACKGROUND: Standards in treatment of acute cholecystitis (AC) in the elderly and high-risk patients has not been established. Our study evaluated the efficacy and safety of B-mode ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) in combination with laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) in elderly and high-risk patients. METHODS: Our study enrolled 35 elderly and high-risk AC patients, hospitalized between January 2010 and April 2014 at the Wenzhou People's Hospital. The patients underwent B-mode ultrasound guided PTGD and LC (PTGD + LC group). As controls, a separate group of 35 elderly and high-risk AC patients who underwent LC alone (LC group) during the same period at the same hospital were randomly selected from a pool of 186 such cases. The volume of bleeding, surgery time, postoperative length of stay, conversion rate to laparotomy and complication rates (bile leakage, bleeding, incisional hernia, incision infection, pulmonary infarction and respiratory failure) were recorded for each patient in the two groups. RESULTS: All patients in the PTGD + LC group successfully underwent PTGD. In the PTGD + LC group, abdominal pain in patients was relieved and leukocyte count, alkaline phosphatase level, total bilirubin and carbohydrate antigen 19-9 (CA19-9) decreased to normal range, and alanine aminotransferase and aspartate aminotransferase levels improved significantly within 72 h after treatment. All patients in the PTGD + LC group underwent LC within 6-10 weeks after PTGD. Our study revealed that PTGD + LC showed a significantly higher efficacy and safety compared to LC alone in AC treatment, as measured by the following parameters: duration of operation, postoperative length of hospital stay, volume of bleeding, conversion rate to laparotomy and complication rate (operation time of LC: 55.6 +/- 23.3 min vs. 91.35 +/- 25.1 min; hospitalized period after LC: 3.0 +/- 1.3 d vs. 7.0 +/- 1.7 d; intraoperative bleeding: 28.7 +/- 15.2 ml vs. 60.38 +/- 16.4 ml; conversion to laparotomy: 3 cases vs. 10 cases; complication: 3 cases vs. 8 cases; all P < 0.05 ). CONCLUSION: Our results suggest that B-mode ultrasound-guided PTGD in combination with LC is superior to LC alone for treatment of AC in elderly and high-risk patients, showing multiple advantages of minimal wounding, accelerated recovery, higher safety and efficacy, and fewer complications. PMID- 26156693 TI - [The ISAR-SAFE study]. PMID- 26156694 TI - [Use of echocardiography in critically ill patients: the cardiologist's point of view]. PMID- 26156695 TI - [Use of echocardiography in critically ill patients: the intensivist's point of view]. PMID- 26156696 TI - [Is echocardiography still helpful in cardiac resynchronization therapy?]. AB - Cardiac resynchronization therapy is an established approach for the treatment of patients with heart failure and left ventricular systolic dysfunction. In most centers, these patients are usually evaluated by echocardiography, which allows collecting a number of cardiac anatomical and functional parameters in a non invasive, repeatable way and without exposure to ionizing radiation. However, over the years, clinical studies have sometimes emphasized and sometimes reduced the role of this method in the setting of cardiac resynchronization therapy for cardiac dyssynchrony evaluation, prognostic stratification of patients, optimization of pacing, and follow-up. The purpose of this paper, therefore, is to review the current role of echocardiography before, during and after the implantation of a cardiac resynchronization therapy device. PMID- 26156697 TI - [Nonvalvular atrial fibrillation: data from the Observatory of Cardiovascular Diseases in the province of Trieste (Italy)]. AB - BACKGROUND: Nonvalvular atrial fibrillation (NVAF) is the most common arrhythmia in outpatients and is associated with increased mortality, thromboembolic and hemorrhagic events. Although several international studies have evaluated its prognostic impact in the real world, Italian data are still lacking. Our aim was to define the prevalence, comorbidity, treatment and outcome in a population of "real-life" outpatients with NVAF. METHODS: From 2009 to 2013, 21 282 consecutive patients referred to the Cardiovascular Center of Trieste were enrolled in the study. NVAF was defined in the absence of moderate-to-severe valvular disease, valvular interventions, rheumatic heart disease. Events evaluated in the follow up included mortality, hospitalizations, thromboembolism and hemorrhage. Clinical data and events were derived from the cardiac regional electronic patient records and the ICD-9 hospital discharge records. RESULTS: 3379 patients (15.8%) had NVAF (35.6% paroxysmal, 34.5% persistent, 29.9% permanent); compared to the general population these patients were older, predominantly male, with hypertension, diabetes and history of stroke/transient ischemic attack and heart failure. Oral anticoagulant therapy was prescribed in 54% of cases, above all in persistent or permanent forms, in patients with higher CHA2DS2-VASc score and younger age. The rate of all-cause mortality, cardiovascular hospitalization, thromboembolic and hemorrhagic events during follow-up was higher in patients with NVAF than in the general population. The use of oral anticoagulant therapy reduced the incidence of thromboembolic events. CHA2DS2-VASc score emerged as an independent predictor of thromboembolic events in patients with paroxysmal (35% higher risk), persistent (40% higher risk) and permanent atrial fibrillation (34% higher risk than patients without atrial fibrillation). CONCLUSIONS: In "real-life" outpatients NVAF is associated with older age, more comorbidities and increased cardiovascular events. CHA2DS2-VASc and HAS-BLED scores predict accurately the risk for thromboembolic and hemorrhagic events. Oral anticoagulation reduces thromboembolic events, but its use is limited to just half of the patients. PMID- 26156698 TI - [MGuard Dacron mesh-covered stent implantation in patients with ST-elevation myocardial infarction and high thrombotic burden: in-hospital and long-term outcome in a single high-volume center]. AB - BACKGROUND: The MGuard (MG) is a stainless-steel closed cell stent covered with an ultra-thin polymer mesh sleeve, which has the purpose of ensuring reduced distal embolization of thrombotic material, thus lowering the risk of no reflow/slow-flow phenomena. Only few data are available that evaluated the usefulness of the MG stent in patients with ST-elevation myocardial infarction (STEMI) with a high thrombotic burden. METHODS: We prospectively collected data of patients presenting with STEMI and high thrombotic burden (thrombus burden grade 4 or 5 according to the TIMI score) who underwent primary percutaneous coronary intervention (PCI) with MG stent implantation in our center. Lesions involving a bifurcation or very calcified and tortuous vessels were not included. Final TIMI 3 flow, normal myocardial blush grade (MBG), and complete ST-segment resolution were defined as short-term endpoints, whereas major adverse cardiovascular events were evaluated during follow-up. RESULTS: From August 2008 to June 2013, the MG stent was implanted in 104 (9.3%) of 1108 patients who underwent primary PCI. Cardiogenic shock on admission was present in 4 patients (3.8%). Final TIMI 3 flow was achieved in 97.1% of patients, MBG 3 in 56.7%, and regression of ST-segment elevation >=70% within 90 min was recorded in 64.4% of patients. In-hospital mortality was 2.9% (n=3), and at a mean follow-up of 455+/ 430 days overall major adverse cardiovascular events were 11 (10.6%). Cardiac death occurred in 5 patients (4.9%) and stent thrombosis in 2 (1.9%). CONCLUSIONS: In selected patients with STEMI undergoing primary PCI, the use of the mesh-covered MG stent in vessels with high thrombotic burden despite thrombus aspiration was effective and safe both immediately and at mid-term follow-up. PMID- 26156699 TI - [Spontaneous coronary artery dissection treated by intravascular ultrasound guided percutaneous coronary intervention: case report and review of the literature]. AB - Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic coronary artery disease, which typically affects women with a low cardiovascular risk profile, and its prevalence as a cause of acute coronary syndrome and sudden death is probably under-recognized. The pathophysiology of SCAD consists essentially in the formation of an intramural hematoma, with or without intimal tear, which causes luminal compression and obstruction. The most used technique for the diagnosis of SCAD is coronary angiography. Intravascular imaging tools, such as intravascular ultrasound and optical coherence tomography, provide a more accurate characterization of the coronary wall, allowing diagnosis when angiography is unclear. We present the case of a young woman admitted with typical chest pain associated with electrocardiographic changes and elevated cardiac troponin I. PMID- 26156700 TI - [The worst complication during percutaneous coronary intervention: left main coronary artery dissection]. AB - Although rare, left main coronary artery dissection is a cause of periprocedural mortality during percutaneous coronary interventions. We report a case of iatrogenic dissection of the left main coronary artery causing cardiogenic shock, treated by extracorporeal membrane oxygenation (ECMO) support and later on by multiple balloon angioplasty and drug-eluting stent deployment, due to clinical worsening despite patent left coronary arteries with preserved good TIMI flow grade. We also reviewed the management strategies of this complication reported in the literature. PMID- 26156701 TI - [Ventricular aneurysm as a complication of giant cell myocarditis]. AB - Ventricular aneurysm as late complication has been described in cardiac sarcoidosis and occasionally in giant cell myocarditis. The images from the present case of ventricular aneurysm formation as a late complication of giant cell myocarditis underline a potential cause of sudden arrhythmic death in patients who survive this life-threatening condition in the absence of recurrent inflammation and with preserved left ventricular ejection fraction. Follow-up with cardiac magnetic resonance can detect small aneurysms, and an implantable cardioverter-defibrillator may be considered when this complication occurs. PMID- 26156704 TI - "Living in a Shell of Something I'm Not": Transsexuality, Medical Ethics, and the Judeo-Christian Culture. AB - A surgeon participating in a 2008 congress on the topic of trans-identified people posed the question of whether doctors would have to defend themselves when "judgment day" comes for having employed surgical means to turn men into women or vice versa? What might be viewed as a certain level of (medical) irrationality surrounding transgender life, coupled with widely documented cases of violence directed at these groups may well partly be attributable to the deeply internalized doctrine of creation in Judeo-Christian culture. Objections, however, to the use of transgender medicine "in the name of normalization" cannot relate to the biblical tradition, for there is no normative concept of gender and no text whose scope is to articulate theory of gender. In the vast expanse and freedom of the Judeo-Christian creator there is space for diversity, variations, and, above all, for the development of individual freedom. PMID- 26156705 TI - Serotonin-immunoreactivity in the ventral nerve cord of Pycnogonida--support for individually identifiable neurons as ancestral feature of the arthropod nervous system. AB - BACKGROUND: The arthropod ventral nerve cord features a comparably low number of serotonin-immunoreactive neurons, occurring in segmentally repeated arrays. In different crustaceans and hexapods, these neurons have been individually identified and even inter-specifically homologized, based on their soma positions and neurite morphologies. Stereotypic sets of serotonin-immunoreactive neurons are also present in myriapods, whereas in the investigated chelicerates segmental neuron clusters with higher and variable cell numbers have been reported. This led to the suggestion that individually identifiable serotonin-immunoreactive neurons are an apomorphic feature of the Mandibulata. To test the validity of this neurophylogenetic hypothesis, we studied serotonin-immunoreactivity in three species of Pycnogonida (sea spiders). This group of marine arthropods is nowadays most plausibly resolved as sister group to all other extant chelicerates, rendering its investigation crucial for a reliable reconstruction of arthropod nervous system evolution. RESULTS: In all three investigated pycnogonids, the ventral walking leg ganglia contain different types of serotonin-immunoreactive neurons, the somata of which occurring mostly singly or in pairs within the ganglionic cortex. Several of these neurons are readily and consistently identifiable due to their stereotypic soma position and characteristic neurite morphology. They can be clearly homologized across different ganglia and different specimens as well as across the three species. Based on these homologous neurons, we reconstruct for their last common ancestor (presumably the pycnogonid stem species) a minimal repertoire of at least seven identified serotonin-immunoreactive neurons per hemiganglion. Beyond that, each studied species features specific pattern variations, which include also some neurons that were not reliably labeled in all specimens. CONCLUSIONS: Our results unequivocally demonstrate the presence of individually identifiable serotonin immunoreactive neurons in the pycnogonid ventral nerve cord. Accordingly, the validity of this neuroanatomical feature as apomorphy of Mandibulata is questioned and we suggest it to be ancestral for arthropods instead. The pronounced disparities between the segmental pattern in pycnogonids and the one of studied euchelicerates call for denser sampling within the latter taxon. By contrast, overall similarities between the pycnogonid and myriapod patterns may be indicative of single cell homologies in these two taxa. This notion awaits further substantiation from future studies. PMID- 26156706 TI - Redox engineering by ectopic expression of glutamate dehydrogenase genes links NADPH availability and NADH oxidation with cold growth in Saccharomyces cerevisiae. AB - BACKGROUND: Cold stress reduces microbial growth and metabolism being relevant in industrial processes like wine making and brewing. Knowledge on the cold transcriptional response of Saccharomyces cerevisiae suggests the need of a proper redox balance. Nevertheless, there are no direct evidence of the links between NAD(P) levels and cold growth and how engineering of enzymatic reactions requiring NAD(P) may be used to modify the performance of industrial strains at low temperature. RESULTS: Recombinant strains of S. cerevisiae modified for increased NADPH- and NADH-dependent Gdh1 and Gdh2 activity were tested for growth at low temperature. A high-copy number of the GDH2-encoded glutamate dehydrogenase gene stimulated growth at 15 degrees C, while overexpression of GDH1 had detrimental effects, a difference likely caused by cofactor preferences. Indeed, neither the Trp(-) character of the tested strains, which could affect the synthesis of NAD(P), nor changes in oxidative stress susceptibility by overexpression of GDH1 and GDH2 account for the observed phenotypes. However, increased or reduced NADPH availability by knock-out or overexpression of GRE3, the NADPH-dependent aldose reductase gene, eliminated or exacerbated the cold growth defect observed in YEpGDH1 cells. We also demonstrated that decreased capacity of glycerol production impairs growth at 15 but not at 30 degrees C and that 15 degrees C-grown baker's yeast cells display higher fermentative capacity than those cultivated at 30 degrees C. Thus, increasing NADH oxidation by overexpression of GDH2 would help to avoid perturbations in the redox metabolism induced by a higher fermentative/oxidative balance at low temperature. Finally, it is shown that overexpression of GDH2 increases notably the cold growth in the wine yeast strain QA23 in both standard growth medium and synthetic grape must. CONCLUSIONS: Redox constraints limit the growth of S. cerevisiae at temperatures below the optimal. An adequate supply of NAD(P) precursors as well as a proper level of reducing equivalents in the form of NADPH are required for cold growth. However, a major limitation is the increased need of oxidation of NADH to NAD(+) at low temperature. In this scenario, our results identify the ammonium assimilation pathway as a target for the genetic improvement of cold growth in industrial strains. PMID- 26156707 TI - Exertional rhabdomyolysis, profound lactic acidosis, and acute kidney injury in a young boy: Answers. PMID- 26156708 TI - Exertional rhabdomyolysis, profound lactic acidosis, and acute kidney injury in a young boy: Questions. PMID- 26156709 TI - Sleep-disordered breathing in children with chronic kidney disease. AB - BACKGROUND: The aim of our study was to ascertain the prevalence and type of sleep-disordered breathing (SDB) in paediatric patients with severe chronic kidney disease (CKD) based on the results of polysomnograms (PSGs). METHODS: Overnight PSGs were conducted on children with CKD stages 3-5 (dialysis dependent). Data were collected on patient demographics from the medical records. Study participants and/or their caregivers completed the paediatric modification of the Epworth Sleepiness Scale Score, the Pediatric Sleep Questionnaire (PSQ) and the Pediatric Quality of Life Inventory at the time of the PSG. RESULTS: Nineteen children were included in the study, of whom seven were on dialysis. The median (interquartile range) age at the time of the PSG was 13.5 (5.4-16.5) years, and eight (42%) of the children were male. There was a 37% (n = 7) prevalence of SDB in this cohort based on the PSG results. Central sleep apnea and obstructive sleep apnea were found in three children each. The PSQ scores did not correlate with the obstructive apnea-hypopnea index. CONCLUSIONS: There was a high prevalence of SDB in this cohort of children with CKD. The PSG and validated sleep questionnaires yielded discordant results, reinforcing the limitations of diagnosing SDB in the CKD population based solely on sleep questionnaires. PMID- 26156710 TI - Predictors of treatment failure for non-severe childhood pneumonia in developing countries--systematic literature review and expert survey--the first step towards a community focused mHealth risk-assessment tool? AB - BACKGROUND: Improved referral algorithms for children with non-severe pneumonia at the community level are desirable. We sought to identify predictors of oral antibiotic failure in children who fulfill the case definition of World Health Organization (WHO) non-severe pneumonia. Predictors of greatest interest were those not currently utilized in referral algorithms and feasible to obtain at the community level. METHODS: We systematically reviewed prospective studies reporting independent predictors of oral antibiotic failure for children 2-59 months of age in resource-limited settings with WHO non-severe pneumonia (either fast breathing for age and/or lower chest wall indrawing without danger signs), with an emphasis on predictors not currently utilized for referral and reasonable for community health workers. We searched PubMed, Cochrane, and Embase and qualitatively analyzed publications from 1997-2014. To supplement the limited published evidence in this subject area we also surveyed respiratory experts. RESULTS: Nine studies met criteria, seven of which were performed in south Asia. One eligible study occurred exclusively at the community level. Overall, oral antibiotic failure rates ranged between 7.8-22.9%. Six studies found excess age adjusted respiratory rate (either WHO-defined very fast breathing for age or 10 15 breaths/min faster than normal WHO age-adjusted thresholds) and four reported young age as predictive for oral antibiotic failure. Of the seven predictors identified by the expert panel, abnormal oxygen saturation and malnutrition were most highly favored per the panel's rankings and comments. CONCLUSIONS: This review identified several candidate predictors of oral antibiotic failure not currently utilized in childhood pneumonia referral algorithms; excess age specific respiratory rate, young age, abnormal oxygen saturation, and moderate malnutrition. However, the data was limited and there are clear evidence gaps; research in rural, low-resource settings with community health workers is needed. PMID- 26156711 TI - Alternatives to autograft evaluated in a rabbit segmental bone defect. AB - PURPOSE: This study was designed to identify strategies for treating bone defects that can be completed on the day of surgery. METHODS: Forty New Zealand white rabbits with unilateral rabbit radius segmental defects (15 mm) were treated with commercially available scaffolds containing either demineralised bone matrix (DBM) or a collagen/beta-tricalcium phosphate composite (Col:beta-TCP); each scaffold was combined with either bone marrow aspirate (BMA) or concentrated BMA (cBMA). Bone regeneration was assessed through radiographic and histological analyses. RESULTS: The concentration of nucleated cells, colony-forming unit fibroblasts and platelets were increased and haematocrit concentration decreased in cBMA as compared to BMA (p < 0.05). Radiographic analyses of bone formation and defect bridging demonstrated significantly greater bone regeneration in the defects treated with DBM grafts as compared to Col:beta-TCP grafts. The healing of bones treated with Col:beta-TCP was improved when augmented with cBMA. CONCLUSIONS: Scaffolds containing either DBM or Col:beta-TCP with BMA or cBMA are effective same-day strategies available to clinicians for the treatment of bone defects; the latter scaffold may be more effective if combined with cBMA. PMID- 26156712 TI - The role of platelet rich plasma in management of fracture neck femur: new insights. AB - PURPOSE: The aim of this study is evaluation of the efficacy of the use of platelet rich plasma (PRP) in management of femoral neck fractures. MATERIALS AND METHODS: This is a prospective study that was conducted between February 2010 and March 2013. A total of 60 patients were included in this study, categorized randomly into two groups. Group A included fracture neck femur treated by closed reduction and internal fixation with three cannulated screws and group B by addition of PRP to internal fixation. We planned to compare time of healing, need for revision and incidence of complications between the two groups. RESULTS: Union occurred in 53 patients (88.33 %) in both groups, 25 cases (83.3 %) in group A and 28 cases (93.3 %) in group B, including three cases (5 %) with avascular necrosis (AVN): two in group A (6.7 %) and one case in group B (3.3 %).Revision surgery was done for six cases (20 %) in group A and for two cases (6.7 %) in group B. In both groups, all united cases had good to excellent clinical outcome as regards Harris hip score (HHS) at the end of the follow up. CONCLUSION: Despite advances in surgical techniques and medical care, the risk of nonunion and avascular necrosis (AVN) after treatment of femoral neck fractures have not been changed appreciably in the last 50 years. Results of this study generally showed that both the median clinical and radiographic healing time were lower in group B compared to group A. PMID- 26156713 TI - Surgical site infection in hand surgery. AB - PURPOSE: As ambulatory surgery becomes increasingly common, there is growing interest in assessing, monitoring, and tracking complications that occur secondary to outpatient procedures. We sought to determine the rates of 14- and 30-day acute care visits for surgical site infection after outpatient hand surgery, and to identify associated factors. METHODS: Using the California State Ambulatory Surgery database for 2010 and 2011, we identified 44,305 patients undergoing common outpatient hand surgery procedures. Cases were linked to the State Emergency Department and the State Inpatient databases for postoperative acute care visits (e.g. hospitalizations, emergency department or ambulatory surgical visits) related to surgical site infection. RESULTS: Postoperative acute care visits for surgical site infection occurred in 1.7 per 1,000 hand surgery procedures (0.17 %) at 14 days, and 3.3 per 1,000 (0.33 %) at 30 days. Thirty-day infection rates were lowest after ganglion cyst (0.15 %) and deQuervain surgery (0.25 %), and highest following cubital tunnel release (0.56 %) and trapeziometacarpal arthroplasty (0.49 %). Fifty-three percent of postoperative visits were treated in the emergency department setting, 37 % in the inpatient setting, and 10 % required an additional outpatient surgical procedure. Patients with government-funded insurance-Medicaid in particular-and those residing in rural areas had higher odds of postoperative acute care visits for surgical site infection. Diabetes, obesity, and tobacco use were not associated with increased risk for infection leading to an acute care visit. CONCLUSION: The rates of postoperative acute care visits for surgical site infection after ambulatory hand procedures are low but not negligible-particularly given how common hand surgery is, and the fact that many of these events entail hospitalizations or additional ambulatory procedures. Reasons for the increased risk of acute care visits for infection among publicly insured and rural patients merit additional research. PMID- 26156714 TI - Three dimensional radiological imaging of normal lower-limb alignment in children. AB - PURPOSE: Our study aimed at evaluating age- and gender-specific references describing lower-limb alignment in a large population of children using an accurate and reliable method (EOS 2D/3D). METHODS: From our database, we selected 523 EOS records suitable for 3D modelling representing age groups between two and 16 years in which no relevant deviation influencing lower-limb biomechanics could be observed (the majority of the examined population had mild scoliosis). We performed reconstruction of both lower limbs, thus obtaining the value of the mechanical tibiofemoral angle (mTFA) and the femoral mechanical axis-femoral shaft angle (FM-FS) and calculated the anatomical tibiofemoral angle (aTFA) from previous parameters. Statistical analysis was carried out using the Kolmogorov Smirnov test, Spearman correlation, regression analysis and Welch test. RESULTS: The aTFA reaches its maximum by the age of three years: 13.07 degrees in boys and 10.73 degrees in girls; it then varies ~4.44 degrees in both genders. By the age of three years, the mTFA reaches 8.04 degrees in boys and 4.85 degrees in girls; it starts to decrease to -1.47 degrees in boys and 0.13 degrees in girls. By the age of three years, FM-FS increases to 5.02 degrees in boys, then fluctuates at ~4.08 degrees , while in girls, it increases to 5.87 degrees , then fluctuates at ~4.24 degrees . CONCLUSIONS: The pattern found in this study confirms the results of previous publications investigating Caucasian populations; however, absolute values differ significantly in several cases. PMID- 26156715 TI - Myocardial ischaemia after hip and knee arthroplasty: incidence and risk factors. AB - PURPOSE: Because the occurrence of postoperative myocardial ischaemia (MI) predicts subsequent cardiac morbidity and mortality, we determined the prevalence of and risk factors for MI in hip and knee arthroplasty patients. METHODS: High sensitivity cardiac troponin T (hs-cTnT) was measured on stored samples from postoperative day two in 394 hip and knee arthroplasty patients >= 65 years of age enrolled in the Genetics-InFormatics Trial (GIFT). RESULTS: Fifty-three (13.5 %) participants had MI, of whom only three were diagnosed clinically during their hospitalisation. The risk of MI increased with age [odds ratio (OR) 3.52 per decade, 95 % confidence interval (CI) 2.00-6.19] and diabetes (OR 2.23, 95 % CI 1.04-4.77). MI was rarer with statins (OR 0.74, 95 % CI 0.40-1.35) and more common with hypertension, coronary artery disease and tobacco use, although these were not statistically significant. CONCLUSIONS: Subclinical MI occurs frequently after arthroplasty. Diabetic and elderly patients are at highest risk. PMID- 26156716 TI - Using the anatomical tibial axis for total knee arthroplasty alignment may lead to an internal rotation error. AB - INTRODUCTION: Despite intensive research, current total knee arthroplasty (TKA) designs do not always provide the correct kinematics for the native joint and thus further optimisation is necessary. Several studies support the importance of malrotation of the tibial components in the failure of TKA. We hypothesise that using the anatomical tibial axis (ATA) to align tibial component rotation on the resected tibial surface may lead to an internal rotation error due to relative anterior shift of the lateral articular surface centre compared to the medial one. The aim of this study was to compare the anatomical tibial axis of the physiological tibial joint surface to the resected one. METHOD: Twenty formalin fixed cadaveric knees were obtained for study. After computed tomography scanning the data of each specimen were entered into a standardised coordinate system and virtual bone cuts were performed with 6, 8 and 10 mm resection depths. The positions of the articular surface centres were determined at each resection depth. RESULTS: The lateral articular surface centre had moved anteriorly after the resection by a mean 1.475 mm, while the medial one had not changed significantly. Resecting the tibia at a 6-mm cut and using the transverse tibial axis to align the prosthetic tibial plateau will result in a mean 4.0 degrees (95 % confidence interval, 2.5-5.5 degrees ) of internal rotation compared to the uncut tibia. DISCUSSION: The ATA lies in 6 degrees of external rotation compared to the perpendicular to the posterior tibial condylar axis (PTCA). Graw et al. suggest aligning the tibial component in 10 degrees of external rotation to the latter. Thus, if we accept the above suggestion, the ATA is 4 degrees internally rotated compared to the same line on the resected proximal tibia. These prior studies appear to be in accordance with our findings. CONCLUSIONS: We conclude that using the ATA on the resected tibial surface may contribute to an internal rotation error. PMID- 26156717 TI - Combined supracondylar femoral derotation osteotomy and patellofemoral ligament reconstruction for recurrent patellar dislocation and severe femoral anteversion syndrome: surgical technique and clinical outcome. AB - PURPOSE: Severly increased femoral anteversion is an important risk factor for patellofemoral instability. Recurrent dislocations cause a traumatic disruption of the medial patellofemoral ligament. Therefore a procedure that combines femoral derotation osteotomy and patellofemoral ligament reconstruction should be considered for patients with severely increased femoral anteversion. The aim of the study was to evaluate the subjective and objective outcomes after combined femoral derotation osteotomy and anatomical reconstruction of the MPFL. METHODS: 12 consecutive patients (12 knees) with patellofemoral instability and severely increased femoral anteversion underwent combined femoral derotation osteotomy and anatomical reconstruction of the MPFL. Preoperative radiographic examination included AP and lateral views to assess patella alta. MRI was performed to evaluate trochlear dysplasia and tibial tubercle-trochlear groove (TT-TG) distance. Additionally, MRI assessment of the rotational profile was performed. Evaluation included evaluation of cartilage injuries, preoperative and postoperative physical examination, visual analog scale (VAS), Kujala score, International Knee Documentation Committee score (IKDC), Activity Rating Scale (ARS) and Tegner activity score. RESULTS: The average age at the time of operation was 18.2 years (range, 15-26 years). The average follow-up after operation was 16.4 months postoperatively (range, 12-28 months). No recurrent dislocation occurred. The results showed a significant improvement of the Kujala score, IKDC score and VAS (p < 0.01). The activity level according to the Tegner activity score and ARS did not show statistically significant changes (p = 0.75; p = 1.0). CONCLUSION: Combined anatomical reconstruction of the MPFL and femoral derotation osteotomy resulted in significant improvement of knee function and good patient satisfaction in young patients with severely increased femoral anteversion. No re-dislocation of the patella occured. PMID- 26156718 TI - Comparison of the efficacy of three isolated gastrocnemius recession procedures in a cadaveric model of gastrocnemius tightness. AB - PURPOSE: Many surgical techniques for isolated gastrocnemius recession have been described. The purpose of the present study is to compare their therapeutic efficacy and intrinsic stability on a fresh cadaveric model of gastrocnemius tightness. METHODS: The cadaveric model was established by distracting the knee with spacers composed of low-temperature thermoplastic material, and was identified by the Silfverskiold test. Procedures of gastrocnemius recession described by Barouk, Baumann and Strayer were performed. The lengthening distance and improvement of ankle dorsiflexion were measured. RESULTS: The mean ankle angle of the cadaveric models was -15.4 degrees with the knee fully extended, and 8.4 degrees with the knee flexed. The increased angle achieved by the Strayer procedure was significantly greater than that achieved by the Barouk procedure and the Baumann procedure with one cut (P < 0.05), but similar to that of the Baumann procedure with two cuts (P > 0.05). Compared with the intramuscular lengthening of the gastrocnemius (Baumann and Barouk procedures), the stability of the lengthening after the Strayer procedure was the lowest. CONCLUSION: The three techniques of isolated gastrocnemius recession have different efficacy and stability in cadaver trials, depending on their own anatomical characteristics. Our study supplies an anatomical guide for the selection of a proper procedure. PMID- 26156719 TI - Impact of type of surgery on deep venous thrombi and pulmonary emboli: a look at twenty seven thousand hip fracture patients. AB - PURPOSE: Deep venous thrombi (DVT) and pulmonary emboli (PE) are common complications in hip fracture patients. It is imperative that orthopaedists know the patient risk factors for DVT and PE, including if type of surgery plays a role. To this end, we used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database to identify significant risk factors. METHODS: From the 2006-2011 ACS NSQIP database, 27,441 patients with hip fractures were identified using a Current Procedural Terminology (CPT) code search. DVT and PE complications, type of surgery based on CPT code, patient demographics, medical comorbidities and operative factors were identified for each patient. Fisher's exact tests were used to (1) determine if rates of DVT and PE significantly differed based on type of surgery and (2) identify significant associations between patient factors and development of DVT/PE. These significant factors were then used as covariates in multivariable analysis to determine which risk factors predicted postoperative DVT/PE. RESULTS: Of the 27,441 hip fracture patients, 449 (1.6 %) developed DVT/PE. There was a significant difference in rates of DVT/PE based on surgery (p = 0.015): patients undergoing intramedullary nailing of inter-/peri-/subtrochanteric femoral fractures had the highest rates of DVT/PE (2.06 %). After multivariate analysis, renal failure and recent surgery were significant risk factors for DVT/PE. CONCLUSIONS: This study was the first to show through large, multicentre, prospective data that type of hip fracture surgery impacts rates of DVT/PE. We further identified two additional risk factors orthopaedists should be aware of. Knowing these risk factors will help in peri-operative planning to reduce complications. PMID- 26156720 TI - Medieval orthopaedic history in Germany: Hieronymus Brunschwig and Hans von Gersdorff. AB - Hans von Gerssdorff and Hieronymus Brunschwig, who flourished in Germany in the latter half of the fifteenth century, have both left early printed treatises on Surgery which give excellent woodcuts showing pictures of instruments, operations, and costumes, at the end of the medieval period. Hieronymus Brunschwig or Hieronymus Brunschwygk (ca. 1450 - ca. 1512), was a German surgeon (wundartzot), alchemist and botanist. He was notable for his methods of treatment of gunshot wounds. His most influential book was the Buch der Cirurgia. Gersdorff(1455-1529) was a military surgeon who gained wide experience during 40 years of campaigning and was an expert in the treatment of battlefield injuries. His work covers anatomy, surgery, leprosy, and glossaries of anatomical terms, diseases, and medications. PMID- 26156721 TI - Fixation pattern of conical and cylindrical modular revision hip stems in different size bone defects. AB - PURPOSE: Femoral defects often make it difficult to achieve sufficient fixation of the stem during revision surgery. No clinical studies comparing modular stems are available and differentiated recommendations are rare. The aim of this study was to compare the fixation of different revision stems in an experimental and standardised manner. METHODS: Segmental AAOS type I and III defects were reproduced in four femur pairs and two modular stems of different shape (cylindrical and conical) were implanted. Interfacial stem-bone movements were measured under axial torque application to analyze the stem fixation depending on defect extension. RESULTS: Both stems showed adequate fixation in AAOS type I defect. The defect extension significantly reduced the fixation of both implants. The fixation pattern changed significantly for the cylindrical-shaped stem but was maintained for the conical-shaped stem. CONCLUSIONS: Shape as well as the extension of femoral defect have an impact on primary fixation. A type I defect seems to be bridgeable for both stems albeit in a different way. In contrast, stem-demanding activities during the healing phase have to be avoided for the conical-shaped stem in a type III defect, whereas the cylindrical-shaped stem has already ceased to be sufficiently stable in this case. PMID- 26156722 TI - Has a patient type with peri-prosthetic femoral fractures evolved? AB - PURPOSE: Peri-prosthetic fractures (PPF) have been showing a constant increase. The typical patient described in the SOFCOT symposium in 2005 with PPF was an elderly 77-year-old woman with hip athroplasty (HA). The purpose of this study was to actualize the characteristics of this population. Our hypothesis is that patient type remains a female, but much older, with an equal distribution between HA and knee arthroplasty (KA). METHODS: All cases of PPF were retrospectively gathered during an 18 month period. Besides regular epidemiologic data, we noted autonomy level (Parker, Devane), residence and dependence (Katz), the type of implant, of fracture, the severity of fracture, the onset and the state of solidity of the prosthesis. RESULTS: The series consisted of 81 patients (58 F, 23 M) (81 fractures), mean age of 82.2 years; 3.5% of them were admits from the emergency admits; and 69.1% lived at home. Parker's mean score was 4.6, Devane's mean score was 1.8 and Katz's mean score was 4.2. There were totals of 46 HA fractures and 39 total knee arthroplasty (TKA) of which four were inter prosthetic and three were either KA or proximal osteosynthesis. Onset before fracture for HA was 12.1 years, 7.9 years for KA, and 10.2 years for all series. Patients were younger for HA (80.8 years) than for KA (84.1 years). The fracture was mostly noticed in the third proximal (49.4%), spiral segment (44.5%) and around the implant, while 34.8% of loosening was observed for HA versus 7.7% for KA. DISCUSSION-CONCLUSION: The patient type has evolved confirming our hypothesis: they are always a female more than 82 years old with a number of fractures on KA similar to that of HA. The patients lived at home, had some autonomy, were somewhat independent in their daily activities but sedentary. Fractures were mostly on the third proximal femur, spiral segment and around the implant. PPF remains rare and a theoretical increase is yet to be confirmed. LEVEL OF EVIDENCE: prospective study type IV, cohort study. PMID- 26156723 TI - In-hospital cost comparison between the standard lateral and supercapsular percutaneously-assisted total hip surgical techniques for total hip replacement. AB - PURPOSE: The purpose of this study was to compare the in-hospital costs associated with the tissue-sparing supercapsular percutaneously-assisted total hip (SuperPath) and traditional Lateral surgical techniques for total hip replacement (THR). METHODS: Between April 2013 and January 2014, in-hospital costs were reviewed for all THRs performed using the SuperPath technique by a single surgeon and all THRs performed using the Lateral technique by another surgeon at the same institution. RESULTS: Overall, costs were 28.4% higher in the Lateral group. This was largely attributable to increased costs associated with transfusion (+92.5%), patient rooms (+60.4%), patient food (+62.8%), narcotics (+42.5%), physical therapy (+52.5%), occupational therapy (+88.6%), and social work (+92.9%). The only costs noticeably increased for SuperPath were for imaging (+105.9%), and this was because the SuperPath surgeon performed intraoperative radiographs on all patients while the Lateral surgeon did not. CONCLUSIONS: The use of the SuperPath technique resulted in in-hospital cost reductions of over 28%, suggesting that this tissue-sparing surgical technique can be cost-effective primarily by facilitating early mobilisation and patient discharge even during a surgeon's initial experience with the approach. PMID- 26156724 TI - Clinical experience with arthroscopically-assisted repair of peripheral triangular fibrocartilage complex tears in adolescents-technique and results. PMID- 26156725 TI - The use of navigation in medial opening wedge high tibial osteotomy can improve tibial slope maintenance and reduce radiation exposure. AB - PURPOSES: We sought to determine the usefulness and the disadvantages of the navigation in medial opening wedge high tibial osteotomy (MOWHTO) compared to the conventional technique, in terms of target coronal alignment achievement, tibial slope maintenance, radiation exposure and operative time. METHODS: We retrospectively compared 40 knees treated with navigated MOWHTO by one surgeon with 20 knees treated with conventional MOWHTO by another surgeon. Screw length of the plate was predetermined using validated simple algorithms only in the navigation group to facilitate the operation. The acceptable range of the postoperative coronal alignment was defined as 2 degrees -6 degrees of the mechanical tibiofemoral angle (mTFA) and 55%-70% of the weight loading line coordinate (WLL). The proportion of the coronal alignment outlier, posterior tibial slope change, fluoroscopy time and operative time were compared. RESULTS: The coronal alignment outliers were fewer in the navigation group, but the differences were not significant (mTFA outlier 18% vs. 30%, p = 0.326; WLL outlier 20% vs. 30%, p = 0.519). Tibial slope was maintained in the navigation group (+0.3 degrees , p = 0.732), whereas increased in the conventional group (+3 degrees , p < 0.001). The fluoroscopy time was shorter in the navigation group (10.4 seconds vs. 24.8 seconds, p < 0.001). The operative time was comparable in both groups (41.3 minutes vs. 39.2 minutes, p = 0.232). CONCLUSIONS: The use of navigation can improve tibial slope maintenance and reduce radiation exposure in MOWHTO, without considerable extension of operative time by optimising the surgical technique. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26156726 TI - Is height the best predictor for adequacy of semitendinosus-alone anterior cruciate ligament reconstruction? A study of hamstring graft dimensions and anthropometric measurements. AB - PURPOSE: To predict adequacy of semitendinosus (ST) graft dimension for ACLR from anthropometric measures. INTRODUCTION: Single tendon harvest for autograft hamstring ACLR could be beneficial to limit donor site morbidity; however, concerns for reconstruction failure based upon inadequate graft size may limit this surgical technique. METHODOLOGY: To predict adequacy, prospectively, 108 patients who underwent ACLR by hamstring graft (STG graft) were enrolled for the study. Mean age was 33.028 years +/- 9.539 SD (14-59) with 88 males and 20 females. Anthropometric measurements (height, weight, BMI, thigh and total limb length) and intraoperative data (graft dimensions and bone tunnel measurements) were collected for analysis. Semitendinosus graft can be used as 3-strand (ST3) or 4-strand (ST4) graft. Adequacy criteria for ST3 and ST4 graft dimensions were determined from data analysis. SPSS (v.17) Pearson's correlation coefficient and ROC curves were used for statistical analyses. RESULTS: A total of 74 out of 108 patients (68.52 %) had adequate graft dimensions for ST3 reconstruction. Height equal or greater than 158 cm was predictive of adequate graft for ST3 reconstruction. Only 23 patients (21.3 %) had adequate graft dimensions for ST4 reconstruction. Height equal or greater than 170 cm was predictive of adequate graft for ST4 reconstruction. Height variable had the highest ROC curve area of 0.840 and 0.910 for both ST3 graft and ST4 graft, respectively. Hence, height was used as best predictor to determine adequacy of the graft. CONCLUSION: Height can be predictive of adequate graft for single tendon ACL reconstruction. PMID- 26156727 TI - Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. AB - PURPOSE: The purpose of this study is to assess safety and feasibility of intradiscal bone marrow concentrate (BMC) injections to treat discogenic pain as an alternative to surgery. METHODS: A total of 26 patients (11 male, 15 female, aged 18-61 years, 13 single level, 13 two level) that met inclusion criteria of chronic (> 6 months) discogenic low back pain, degenerative disc pathology assessed by magnetic resonance imaging (MRI) with modified Pfirrmann grade of IV VII at one or two levels, candidate for surgical intervention (failed conservative treatment and radiologic findings) and a visual analogue scale (VAS) pain score of 40 mm or more at initial visit. Initial Oswestry Disability Index (ODI) and VAS pain score average was 56.5 % and 80.1 mm (0-100), respectively. Adverse event reporting, ODI score, VAS pain score, MRI radiographic changes, progression to surgery and cellular analysis of BMC were noted. Retrospective cell analysis by flow cytometry and colony forming unit-fibroblast (CFU-F) assays were performed to characterise each patient's BMC and compare with clinical outcomes. The BMC was injected into the nucleus pulposus of the symptomatic disc(s) under fluoroscopic guidance. Patients were evaluated clinically prior to treatment and at three, six, 12 and 24 months and radiographically prior to treatment and at 12 months. RESULTS: There were no complications from the percutaneous bone marrow aspiration or disc injection. Of 26 patients, 24 (92 %) avoided surgery through 12 months, while 21 (81 %) avoided surgery through two years. Of the 21 surviving patients, the average ODI and VAS scores were reduced to 19.9 and 27.0 at three months and sustained to 18.3 and 22.9 at 24 months, respectively (p <= 0.001). Twenty patients had follow-up MRI at 12 months, of whom eight had improved by at least one Pfirrmann grade, while none of the discs worsened. Total and rate of pain reduction were linked to mesenchymal stem cell concentration through 12 months. Only five of the 26 patients elected to undergo surgical intervention (fusion or artificial disc replacement) by the two year milestone. CONCLUSIONS: This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC, with durable pain relief (71 % VAS reduction) and ODI improvements (> 64 %) through two years. PMID- 26156728 TI - Equivalent results of medial and lateral parapatellar approach for total knee arthroplasty in mild valgus deformities. AB - PURPOSE: When performing total knee arthroplasty (TKA) in valgus knee deformities, a medial or lateral parapatellar approach can be performed, but the lateral approach is often considered technically more difficult. The purpose of this study was to compare intra-operative, early clinical and radiological outcomes of medial and lateral parapatellar approaches for TKA in the setting of moderate knee valgus (<10 degrees ). METHODS: We prospectively analysed 424 knees with pre-operative valgus deformity between 3 degrees and 10 degrees that underwent TKA over an 18-year period; 109 were treated with a medial approach and 315 with a lateral approach. Intra- and post-operative outcomes and complication rates after a minimum follow-up of one year were compared. RESULTS: Tourniquet (p = 0.25) and surgical (p = 0.62) time were similar between groups. The popliteus tendon was released more frequently in the medial-approach group (p = 0.04), while the iliotibial band was released more frequently in the lateral-approach group (p < 0.001). A tibial tuberosity osteotomy was performed more frequently in the lateral- than medial-approach group (p = 0.003). No significant differences in limb alignment (p = 0.78), or Knee Society Score (KSS) knee (p = 0.32) and function (p = 0.47) results were noted based on surgical approach, and complication rates were similar between groups (p = 0.53). CONCLUSIONS: Lateral parapatellar approach is a safe and effective surgical technique for performing TKA in moderately valgus knees. These equivalent early results are encouraging for systematic use of the lateral approach in moderately valgus knees. PMID- 26156729 TI - Long-term survivorship and complication rate comparison of a cementless modular stem and cementless fixed neck stems for primary total hip replacement. AB - PURPOSE: Modular necks used in total hip replacement (THR) have become an increasingly discussed topic with the recent recall of multiple modular systems, but it is anticipated that outcomes for these devices are highly design-specific. The objectives of this study were to determine if the survivorship and complication rates of a specific modular femoral stem (PROFEMUR(r) Z, MicroPort Orthopedics Inc., Arlington, TN, USA) were significantly lower than those of all cementless fixed neck stems in an arthroplasty registry. METHODS: The database of an arthroplasty registry was searched for all patients implanted with a specific modular stem and all those implanted with cementless fixed neck stems. Kaplan Meier survivorship and complication rates were compared between the two groups. RESULTS: The 12-year survivorship of the modular stem (95.8%) was not significantly less than that of all cementless fixed neck stems (96.1%). There was also no difference in revision rates for dislocation, periprosthetic fractures, aseptic loosening or septic loosening between the two groups. CONCLUSIONS: The use of the specific modular stem did not adversely affect long term component survivorship or complication rates when compared to all cementless fixed neck THRs in an arthroplasty registry. PMID- 26156730 TI - Open Achilles tenotomy and posterior capsulotomy for congenital talipes equinovarus. PMID- 26156731 TI - Treating Eyres type IV and V coracoid fracture using the acromion osteotomy approach. AB - PURPOSE: To introduce a surgical method of treating Eyres type IV and V coracoid fracture using the acromion osteotomy approach and to further analyse the clinical effectiveness of this surgical procedure. METHODS: Nine patients were included in this study with a mean follow-up time of 23.3 months (range, 14.0 34.0 months). Patients were evaluated with use of the Constant score, the Simple Shoulder Test (SST) score and a visual analogue scale (VAS) pain score. Moreover, the shoulder range of motion was also observed. RESULTS: The mean operation time was 91.6 min with a blood loss volume ranging from 310 to 530 ml. The fractures of eight patients had recovered between 10 and 12 weeks post operation with no signs of infection, screw loosening, plate breaking or other internal fixation failures, while one case had non-union at 34 months' follow-up. The mean Constant score increased from 75.6 points preoperatively to 91.0 points at follow-up. The mean VAS score decreased from 5.3 preoperatively to 1.0 at follow-up, while the average SST score increased from 7.1 points preoperatively to 10.0 points at follow-up. The mean abduction, forward flexion, external rotation, internal rotation and backward extension angles were 162 degrees , 159 degrees 50 degrees , 55 degrees and 47 degrees . Five cases were classified as excellent, three cases were marked as good and one case was classified as fair. CONCLUSIONS: Treating coracoid fracture through the approach of acromion osteotomy could be an effective treatment option with minimise damages. PMID- 26156732 TI - Predicting length of stay after robotic partial nephrectomy. AB - INTRODUCTION: To investigate factors predictive of length of stay (LOS) after robotic partial nephrectomy (RPN) in an effort to identify patients suitable for RPN with overnight stay at outpatient surgical facilities. MATERIALS AND METHODS: Retrospective chart review of patients who underwent RPN at Memorial Sloan Kettering Cancer Center from January 2007 to July 2012 was conducted. Univariate and multivariate analyses were performed to identify the main predictors of LOS. The discrimination of the multivariate model was measured using the area under the curve (AUC); tenfold cross-validation was performed to correct for over-fit. RESULTS: One hundred and eighty-six patients were included in the analysis; 84 (45 %) had LOS of <=1 day (median LOS 2 day; interquartile range 1-2). On univariate analysis, preoperative variables associated with LOS > 1 included larger tumors (P < 0.0001), lower estimated glomerular filtration rate (P = 0.003), older age (P = 0.006), female gender (P = 0.035), and higher comorbidity score (P = 0.015); operative variables associated with LOS > 1 day included greater estimated blood loss (P < 0.0001) and longer operative (P < 0.0001) and ischemia (P < 0.0001) times. The AUC of the preoperative model was 0.61 (95 % CI 0.52-0.69) after tenfold cross-validation. CONCLUSIONS: LOS after RPN is influenced by age, gender, medical comorbidities, and tumor size. However, when analyzed retrospectively, these factors had limited ability to predict LOS after RPN with sufficient accuracy to develop a prediction tool. PMID- 26156733 TI - Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial. AB - BACKGROUND: Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant. OBJECTIVE: The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)D(total). DESIGN: This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D <=20 ng/mL (by immunoassay) and administered 50,000 IU ergocalciferol/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure. RESULTS: On-study 25(OH)D(total) was assessed by liquid chromatography-tandem mass spectrometry. In the treated group, 25(OH)D(total) rose from 18 +/- 7 to 43 +/- 12 ng/mL (P < 0.001) with no change in the placebo group. Despite this increase, at 12 wk, there were no between-group differences in either insulin response or insulin sensitivity; nor were there differences in any measured secondary endpoints. There was no evidence of effect modification by sex, race, glucose tolerance status, baseline 25(OH)D(total), or BMI. CONCLUSION: In healthy persons with low 25(OH)D(total), ergocalciferol administration for 12 wk normalizes 25(OH)D(total) but does not improve insulin secretion, insulin sensitivity, or other markers of metabolic health. PMID- 26156734 TI - Vitamin and carotenoid intake and risk of head-neck cancer subtypes in the Netherlands Cohort Study. AB - BACKGROUND: Head and neck cancer (HNC) is the seventh most-common type of cancer worldwide. Evidence regarding the potential protective effect of vitamins and carotenoids on HNC is limited and mostly based on case-control studies. OBJECTIVE: We evaluated the association of intake of dietary vitamins C and E (including supplementation) and the most-common carotenoids (alpha-carotene, beta carotene, lutein plus zeaxanthin, lycopene, and beta-cryptoxanthin) and risk of HNC and HNC subtypes in a large prospective study. DESIGN: The Netherlands Cohort Study included 120,852 participants. For efficiency reasons, a case-cohort design was used. At baseline in 1986, participants completed a food-frequency questionnaire. A subcohort was randomly selected from the total cohort. After 20.3 y of follow-up, 3898 subcohort members and 415 HNC cases [131 oral cavity cancer (OCCs), 88 oro-/hypopharyngeal cancer (OHPs), and 193 laryngeal cancer cases] were available for analysis. Rate ratios and 95% CIs for highest (quartile 4) compared with lowest (quartile 1) quartiles of vitamin and carotenoid intake were estimated by using the Cox proportional hazards model. RESULTS: A strong inverse association was shown between vitamin C and HNC overall (multivariable adjusted rate ratio for quartile 4 compared with quartile 1: 0.39; 95% CI: 0.23, 0.66; P-trend < 0.001), OCC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.35; 95% CI: 0.16, 0.77; P-trend < 0.05), and OHPC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.29; 95% CI: 0.12, 0.67; P-trend < 0.01). No statistically significant results were shown for vitamin E, alpha-carotene, beta-carotene, lycopene, and lutein plus zeaxanthin. The association of vitamin E and HNC was modified by alcohol status (P-interaction = 0.003) with lower risks in alcohol abstainers. CONCLUSIONS: With this study, we show an inverse association between intake of vitamin C and the incidence of HNC and HNC-subtypes. Future research is recommended to investigate the underlying mechanisms and to confirm our results, which may be promising for the prevention of HNC. PMID- 26156735 TI - Dietary intake of soluble fiber and risk of islet autoimmunity by 5 y of age: results from the TEDDY study. AB - BACKGROUND: Deficient soluble fiber intake has been suggested to dysregulate the immune response either directly or through alterations of the microbial composition in the gut. OBJECTIVE: We hypothesized that a high intake of dietary soluble fiber in early childhood decreases the risk of type 1 diabetes (T1D) associated islet autoimmunity. DESIGN: We analyzed 17,620 food records collected between age 9 and 48 mo from 3358 children from the United States and Germany prospectively followed in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. HRs for the development of any/multiple islet autoantibodies (242 and 151 events, respectively) and T1D (71 events) by soluble fiber intake were calculated in Cox regression models and adjusted for potential confounders. RESULTS: There were no statistically significantly protective associations observed between a high intake of soluble fiber and islet autoimmunity or T1D. For example, the adjusted HRs (95% CIs) for high intake (highest compared with lowest quintile) at age 12 mo were 0.90 (0.55, 1.45) for any islet autoantibody, 1.20 (0.69, 2.11) for multiple islet autoantibodies, and 1.24 (0.57, 2.70) for T1D. In analyzing soluble fiber intake as a time-varying covariate, there were also no short-term associations between soluble fiber intake and islet autoimmunity development, with adjusted HRs of 0.85 (0.51, 1.42) for high intake and development of any islet autoantibody, for example. CONCLUSION: These results indicate that the intake level of dietary soluble fiber is not associated with islet autoimmunity or T1D in early life. PMID- 26156736 TI - Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals. AB - BACKGROUND: High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown. OBJECTIVE: We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically. DESIGN: In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence. RESULTS: Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally. CONCLUSIONS: High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification bias. PMID- 26156737 TI - Maternal vitamin D3 supplementation at 50 MUg/d protects against low serum 25 hydroxyvitamin D in infants at 8 wk of age: a randomized controlled trial of 3 doses of vitamin D beginning in gestation and continued in lactation. AB - BACKGROUND: Vitamin D supplementation is recommended for breastfed infants. Maternal supplementation beginning in gestation is a potential alternative, but its efficacy in maintaining infant 25-hydroxyvitamin D [25(OH)D] concentration after birth is unknown. OBJECTIVES: We determined the effect of 3 doses of maternal vitamin D supplementation beginning in gestation and continued in lactation on infant serum 25(OH)D and compared the prevalence of infant serum 25(OH)D cutoffs (>30, >40, >50, and >75 nmol/L) by dose at 8 wk of age. DESIGN: Pregnant women (n = 226) were randomly allocated to receive 10, 25, or 50 MUg vitamin D3/d from 13 to 24 wk of gestation until 8 wk postpartum, with no infant supplementation. Mother and infant blood was collected at 8 wk postpartum. RESULTS: At 8 wk postpartum, mean [nmol/L (95% CI)] infant 25(OH)D at 8 wk was higher in the 50-MUg/d [75 (67, 83)] than in the 25-MUg/d [52 (45, 58)] or 10 MUg/d [45 (38, 52)] vitamin D groups (P < 0.05). Fewer infants born to mothers in the 50-MUg/d group had a 25(OH)D concentration <30 nmol/L (indicative of deficiency) than infants in the 25- and 10-MUg/d groups, respectively (2% compared with 16% and 43%; P < 0.05). Fewer than 15% of infants in the 10- or 25 MUg/d groups achieved a 25(OH)D concentration >75 nmol/L compared with 44% in the 50-MUg/d group (P < 0.05). Almost all infants (~98%, n = 44) born to mothers in the 50-MUg/d group achieved a 25(OH)D concentration >30 nmol/L. At 8 wk postpartum, mean maternal 25(OH)D concentration was higher in the 50-MUg/d [88 (84, 91)] than in the 25-MUg/d [78 (74, 81)] or 10-MUg/d [69 (66, 73)] groups (P < 0.05). CONCLUSIONS: Maternal supplementation beginning in gestation with 50 MUg vitamin D3/d protects 98% of unsupplemented breastfed infants against 25(OH)D deficiency (<30 nmol/L) to at least 8 wk, whereas 10 or 25 MUg vitamin D/d protects only 57% and 84% of infants, respectively. PMID- 26156738 TI - Healthy obesity and objective physical activity. AB - BACKGROUND: Disease risk is lower in metabolically healthy obese adults than in their unhealthy obese counterparts. Studies considering physical activity as a modifiable determinant of healthy obesity have relied on self-reported measures, which are prone to inaccuracies and do not capture all movements that contribute to health. OBJECTIVE: We aimed to examine differences in total and moderate-to vigorous physical activity between healthy and unhealthy obese groups by using both self-report and wrist-worn accelerometer assessments. DESIGN: Cross sectional analyses were based on 3457 adults aged 60-82 y (77% male) participating in the British Whitehall II cohort study in 2012-2013. Normal weight, overweight, and obese adults were considered "healthy" if they had <2 of the following risk factors: low HDL cholesterol, hypertension, high blood glucose, high triacylglycerol, and insulin resistance. Differences across groups in total physical activity, based on questionnaire and wrist-worn triaxial accelerometer assessments (GENEActiv), were examined by using linear regression. The likelihood of meeting 2010 World Health Organization recommendations for moderate-to-vigorous activity (>=2.5 h/wk) was compared by using prevalence ratios. RESULTS: Of 3457 adults, 616 were obese [body mass index (in kg/m2) >=30]; 161 (26%) of those were healthy obese. Obese adults were less physically active than were normal-weight adults, regardless of metabolic health status or method of physical activity assessment. Healthy obese adults had higher total physical activity than did unhealthy obese adults only when assessed by accelerometer (P = 0.002). Healthy obese adults were less likely to meet recommendations for moderate-to-vigorous physical activity than were healthy normal-weight adults based on accelerometer assessment (prevalence ratio: 0.59; 95% CI: 0.43, 0.79) but were not more likely to meet these recommendations than were unhealthy obese adults (prevalence ratio: 1.26; 95% CI: 0.89, 1.80). CONCLUSIONS: Higher total physical activity in healthy than in unhealthy obese adults is evident only when measured objectively, which suggests that physical activity has a greater role in promoting health among obese populations than previously thought. PMID- 26156739 TI - Neuropeptide Y genotype, central obesity, and abdominal fat distribution: the POUNDS LOST trial. AB - BACKGROUND: Neuropeptide Y is a key peptide affecting adiposity and has been related to obesity risk. However, little is known about the role of NPY variations in diet-induced change in adiposity. OBJECTIVE: The objective was to examine the effects of NPY variant rs16147 on central obesity and abdominal fat distribution in response to dietary interventions. DESIGN: We genotyped a functional NPY variant rs16147 among 723 participants in the Preventing Overweight Using Novel Dietary Strategies trial. Changes in waist circumference (WC), total abdominal adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue (SAT) from baseline to 6 and 24 mo were evaluated with respect to the rs16147 genotypes. Genotype-dietary fat interaction was also examined. RESULTS: The rs16147 C allele was associated with a greater reduction in WC at 6 mo (P < 0.001). In addition, the genotypes showed a statistically significant interaction with dietary fat in relation to WC and SAT (P-interaction = 0.01 and 0.04): the association was stronger in individuals with high-fat intake than in those with low-fat intake. At 24 mo, the association remained statistically significant for WC in the high-fat diet group (P = 0.02), although the gene dietary fat interaction became nonsignificant (P = 0.30). In addition, we found statistically significant genotype-dietary fat interaction on the change in total abdominal adipose tissue, visceral adipose tissue, and SAT at 24 mo (P = 0.01, 0.05, and 0.04): the rs16147 T allele appeared to associate with more adverse change in the abdominal fat deposition in the high-fat diet group than in the low fat diet group. CONCLUSION: Our data indicate that the NPY rs16147 genotypes affect the change in abdominal adiposity in response to dietary interventions, and the effects of the rs16147 single-nucleotide polymorphism on central obesity and abdominal fat distribution were modified by dietary fat. PMID- 26156740 TI - Olive oil consumption and risk of type 2 diabetes in US women. AB - BACKGROUND: Olive oil has been shown to improve various cardiometabolic risk factors. However, to our knowledge, the association between olive oil intake and type 2 diabetes (T2D) has never been evaluated in the US population. OBJECTIVE: We aimed to examine the association between olive oil intake and incident T2D. DESIGN: We followed 59,930 women aged 37-65 y from the Nurses' Health Study (NHS) and 85,157 women aged 26-45 y from the NHS II who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by validated food-frequency questionnaires, and data were updated every 4 y. Incident cases of T2D were identified through self-report and confirmed by supplementary questionnaires. RESULTS: After 22 y of follow-up, we documented 5738 and 3914 incident cases of T2D in the NHS and NHS II, respectively. With the use of Cox regression models with repeated measurements of diet and multivariate adjustment for major lifestyle and dietary factors, the pooled HR (95% CI) of T2D in those who consumed >1 tablespoon (>8 g) of total olive oil per day compared with those who never consumed olive oil was 0.90 (0.82, 0.99). The corresponding HRs (95% CIs) were 0.95 (0.87, 1.04) for salad dressing olive oil and 0.85 (0.74, 0.98) for olive oil added to food or bread. We estimated that substituting olive oil (8 g/d) for stick margarine, butter, or mayonnaise was associated with 5%, 8%, and 15% lower risk of T2D, respectively, in the pooled analysis of both cohorts. CONCLUSIONS: Our results suggest that higher olive oil intake is associated with modestly lower risk of T2D in women and that hypothetically substituting other types of fats and salad dressings (stick margarine, butter, and mayonnaise) with olive oil is inversely associated with T2D. PMID- 26156742 TI - Studying dietary phosphorus intake: the challenge of when a gram is not a gram. PMID- 26156741 TI - Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study. AB - BACKGROUND: Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions. OBJECTIVES: Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed. DESIGN: Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips. RESULTS: Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage. CONCLUSIONS: As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer. PMID- 26156744 TI - Mechanisms of integrin and filamin binding and their interplay with talin during early focal adhesion formation. AB - Filamin plays a key role in cellular biomechanics as an actin cross-linker and as a versatile focal adhesion binding partner. It binds directly to integrins, a family of mechanosensitive transmembrane receptors that mediate attachment to several extracellular ligands such as fibronectin, collagen, and laminin. Filamin binds beta-integrin at its cytoplasmic tail, competing with talin, a major integrin activator that plays a chief role in cell adhesion. Herein, we develop molecular dynamics models to study the mechanism of early binding of alphaIIbbeta3 integrin with filamin A (FLNa). Our models predict three important electrostatic interactions and one stabilizing hydrophobic interaction that mediate binding between filamin and integrin. In its native conformation, filamin's integrin binding site is auto-inhibited. Our models help shed light on the role of integrin binding on regulating filamin activation. Finally, the effect of talin on the filamin-integrin interaction is explored and possible scenarios of the interplay among these molecules are examined. PMID- 26156743 TI - Prospective association between dietary folate intake and skin cancer risk: results from the Supplementation en Vitamines et Mineraux Antioxydants cohort. AB - BACKGROUND: The role of folate in skin carcinogenesis is unclear, with experimental data suggesting potentially protective but also deleterious effects. OBJECTIVE: Our main objective was to investigate the prospective association between dietary folate intake and risks of skin cancer (overall), nonmelanoma skin cancer (NMSC), and basal cell carcinoma (BCC). As an exploratory analysis, we also investigated the prospective association between erythrocyte folate concentration and skin cancer risk. DESIGN: In this study, we included 5880 participants in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort (follow-up: 1994-2007) who completed at least six 24-h dietary records during the first 2 y of the study. Associations between sex-specific tertiles of dietary and erythrocyte folate and skin cancer risk were assessed by using multivariate Cox proportional hazards models. RESULTS: After a median follow-up of 12.6 y, 144 incident skin cancers were diagnosed. Dietary folate intake was associated with increased risk of overall skin cancer [HR for tertile 3 compared with tertile 1 (HR(T3vs.T1)): 1.79; 95% CI: 1.07, 2.99; P-trend = 0.03], NMSC (HR(T3vs.T1): 1.85; 95% CI: 1.06, 3.23; P-trend = 0.03), and BCC (HR(T3vs.T1): 1.78; 0.98, 3.24; P-trend = 0.05). This association was observed in women (corresponding P-trend = 0.007, 0.009, and 0.009, respectively) but not in men (P-trend = 0.8, 0.8, and 0.9, respectively). P-interaction values between tertiles of dietary folate intake and sex were 0.04, 0.02, and 0.02 for overall skin cancer, NMSC, and BCC, respectively. Erythrocyte folate concentration was directly associated with increased risk of overall skin cancer (HR(T3vs.T1): 2.54; 95% CI: 0.95, 6.81; P-trend = 0.03), NMSC (HR(T3vs.T1): 3.49; 95% CI: 1.11, 11.0; P-trend = 0.01), and BCC (HR(T3vs.T1): 7.44; 95% CI: 1.57, 35.3; P-trend = 0.004) (men and women combined). CONCLUSIONS: This prospective study suggests an association between dietary folate intake and erythrocyte folate concentration and increased risk of overall skin cancer, NMSC, and BCC. Although several mechanistic hypotheses and 2 previous large prospective studies on BCC are in line with these results, epidemiologic literature is limited, and future research is needed to better elucidate the potential role of folate in the cause of skin cancers. PMID- 26156745 TI - Concomitant occurrence of Mikulicz's disease and immunoglobulin G4-related chronic rhinosinusitis: a clinicopathological study of 12 cases. AB - AIMS: Concomitant occurrence of Mikulicz's disease (MD) and immunoglobulin (Ig)G4 related chronic rhinosinusitis (IgG4-related CRS) is extremely rare. We evaluated the clinicopathological features of MD patients with concomitant IgG4-related CRS (CRS-MD). METHODS AND RESULTS: Twelve CRS-MD patients were evaluated clinically and biopsy samples were taken from the lacrimal/salivary glands (n = 12) and nasal mucosa (n = 7) for assessment of IgG4-positive cells, using immunohistochemical techniques. Similarly, nine MD patients and 10 patients with common CRS were evaluated as controls. CRS-MD patients had higher serum IgG and IgG4 concentrations than MD patients (P < 0.05 for both). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis was prominent in the lacrimal/salivary glands in both groups; however, the magnitude of IgG4-positive plasma cells infiltration in the CRS-MD group was significantly higher compared to the MD group (P = 0.004). Similarly, evaluation of nasal mucosa revealed greater lymphocyte, plasma cell and eosinophil infiltration and lymphoid follicle formation, together with significantly higher IgG4-positive plasma cell infiltration in the CRS-MD group compared to the common CRS group (P = 0.004). CONCLUSIONS: Concomitant MD and IgG4-related CRS were characterized by a combination of IgG4-positive plasma cells infiltration in the lacrimal/salivary glands and the nasal mucosa and increased serum IgG4. PMID- 26156746 TI - Two new dammarane-type triterpene sapogenins from Chinese red ginseng. AB - Two new dammarane-type triterpene sapogenins were isolated from the Chinese red ginseng. The new sapogenins were named as 24,26-dihydroxy-panaxdiol (1) and 24 hydroxy-panaxdiol (2). Their structures were elucidated by the combined analysis of NMR and mass spectrometry as 20(S),25(R)-epoxydammarane-3beta,12beta,24beta,26 tetraol (1) and 20(S),25-epoxydammarane-3beta,12beta,24alpha-triol (2). The complete signal assignments of the two compounds were carried out by 2D NMR spectral and NOE differential spectroscopy analysis. PMID- 26156748 TI - From Lipid Retention to Immune-Mediate Inflammation and Associated Angiogenesis in the Pathogenesis of Atherosclerosis. AB - Atherosclerosis is a leading cause of mortality and long-term morbidity worldwide. It is a lipoprotein-driven disease that leads to plaque formation at focal areas in the arterial blood vessels through intimal inflammation, necrosis, fibrosis, and calcification. Adventitial and intimal angiogenesis contributes to the progression of intimal hyperplasia and the development of a necrotic core. The volatile nature of an atheromatous plaque is responsible for approximately 60% of symptomatic carotid artery diseases and about 75% of acute coronary events. In this review the pathogenesis of atherosclerosis is discussed from the initial step of lipid retention to advanced stages of immune-mediate inflammation and associated angiogenesis. Mechanisms of plaque rupture are also discussed. PMID- 26156747 TI - Enrichment of H3K9me2 on Unsynapsed Chromatin in Caenorhabditis elegans Does Not Target de Novo Sites. AB - Many organisms alter the chromatin state of unsynapsed chromosomes during meiotic prophase, a phenomenon hypothesized to function in maintaining germline integrity. In Caenorhabditis elegans, histone H3 lysine 9 dimethylation (H3K9me2) is detected by immunolabeling as enriched on unsynapsed meiotic chromosomes. Loss of the SET domain protein, MET-2, greatly reduces H3K9me2 abundance and results in germline mortality. Here, we used him-8 mutations to disable X chromosome synapsis and performed a combination of molecular assays to map the sites of H3K9me2 accumulation, evaluate H3K9me2 abundance in germline vs. whole animals, and evaluate the impact of H3K9me2 loss on the germline transcriptome. Our data indicate that H3K9me2 is elevated broadly across the X chromosome and at defined X chromosomal sites in him-8 adults compared with controls. H3K9me2 levels are also elevated to a lesser degree at sites on synapsed chromosomes in him-8 adults compared with controls. These results suggest that MET-2 activity is elevated in him-8 mutants generally as well as targeted preferentially to the unsynapsed X. Abundance of H3K9me2 and other histone H3 modifications is low in germline chromatin compared with whole animals, which may facilitate genome reprogramming during gametogenesis. Loss of H3K9me2 has a subtle impact on the him-8 germline transcriptome, suggesting H3K9me2 may not be a major regulator of developmental gene expression in C. elegans. We hypothesize H3K9me2 may have a structural function critical for germline immortality, and a greater abundance of these marks may be required when a chromosome does not synapse. PMID- 26156749 TI - Reliability and Validity of the Dissociative Experiences Scale Among South Korean Patients With Schizophrenia. AB - The Dissociative Experiences Scale (DES) is the most widely used self-report tool for use with the general population and various clinical entities, including those with schizophrenia. This preliminary study tested the reliability of the DES, especially temporal stability and validity, in patients diagnosed with schizophrenia receiving inpatient or outpatient treatment. The DES was administered at a university-affiliated training hospital in South Korea to a total of 68 patients (39 inpatients and 29 outpatients) whose diagnosis of schizophrenia was confirmed using the Structured Clinical Interview for DSM-IV Axis Disorders. Internal consistency, 4-week test-retest reliability, and validity were calculated. Participants also completed the Childhood Trauma Questionnaire, the Beck Depression Inventory, and the Symptom Checklist Posttraumatic Stress Disorder Scale. Four-week test-retest reliability was moderate (r = .69) and internal consistency was good (Cronbach's alpha = .95). Total score on the DES was correlated with childhood trauma (r = .69, p < .001), posttraumatic symptoms (r = .50, p < .001), and depression (r = .52, p < .001), demonstrating the convergent validity of the scale. Our study confirms the psychometric soundness of the DES among patients with schizophrenia after the acute stage of illness (e.g., 3 weeks after admission), supporting use of the scale for screening and evaluating dissociative symptoms within this population. PMID- 26156750 TI - Fifty million people use computerised self triage. PMID- 26156751 TI - Endomembrane control of cell polarity: Relevance to cancer. AB - The role of polarity in cancer is an emerging research area and loss of polarity is widely considered an important event in cancer. Among the polarity regulating molecules, the small GTPase Cdc42 was extensively studied. Most attention was given to Cdc42 signaling at the plasma membrane, but whether and how Cdc42 is regulated at endomembranes remained poorly understood. Moreover, whether the endomembrane pool of Cdc42 is of any relevance to cell polarity was unknown. In our recent work, we identified a complex between the Golgi matrix protein GM130 and RasGRF and showed that it is responsible for regulating the Golgi pool of Cdc42, but had no effect on the plasma membrane pool of Cdc42. Depletion of GM130 disrupted apico-basal polarity as well as front-rear polarity, indicating that the spatial pool of Cdc42 is functionally relevant. The biomedical relevance of this finding was supported by the observation than GM130 is progressively lost in colorectal cancer. These findings support a role of the endomembrane pool of Cdc42 in cell polarity and point to a potential role of alterations of this pool in cancer. PMID- 26156752 TI - Pharmacodynamic considerations of small molecule targeted therapy for treating B cell malignancies in the elderly. AB - INTRODUCTION: Small molecule inhibitors are currently in various stages of preclinical and clinical trials and are expected to revolutionize the treatment of many neoplastic diseases, including B-cell lymphoid malignancies. AREAS COVERED: This article reviews the chemical structure, mechanisms of action, pharmacodynamic and pharmacokinetic properties, as well as clinical applications of small molecules in the treatment of elderly patients with B-cell hematological malignancies. Bibliographic research covering mainly the period from 2010 until February 2015 was conducted on the MEDLINE database for articles in English. Proceedings of the American Society of Hematology, European Hematology Association and American Society of Clinical Oncology conferences held during the last 5 years were also included. EXPERT OPINION: In the last few years, several preclinical and clinical trials have evaluated many small weight organic molecules which downregulate B-cell receptor (BCR) signaling and act via inhibition of either BCR-associated kinases or cyclin-dependent kinases, or which are antagonists of members of the B-cell lymphoma 2 protein family. Pharmacokinetic profiles of these agents as well as dosage used and adverse events in patients with lymphoid malignancies have been established. Some of these inhibitors satisfy therapeutic modalities as suitable for the elderly patients, including those with chronic lymphocytic leukemia and non-Hodgkin's lymphoma. PMID- 26156753 TI - Kallistatin inhibits TGF-beta-induced endothelial-mesenchymal transition by differential regulation of microRNA-21 and eNOS expression. AB - Kallistatin, an endogenous protein, consists of two structural elements: active site and heparin-binding domain. Kallistatin exerts beneficial effects on fibrosis by suppressing transforming growth factor (TGF)-beta synthesis in animal models. TGF-beta is the most potent inducer of endothelial-mesenchymal transition (EndMT), which contributes to fibrosis and cancer. MicroRNA (miR)-21 is an important player in organ fibrosis and tumor invasion. Here we investigated the potential role of kallistatin in EndMT via modulation of miR-21 in endothelial cells. Human kallistatin treatment blocked TGF-beta-induced EndMT, as evidenced by morphological changes as well as increased endothelial and reduced mesenchymal marker expression. Kallistatin also inhibited TGF-beta-mediated reactive oxygen species (ROS) formation and NADPH oxidase expression and activity. Moreover, kallistatin antagonized TGF-beta-induced miR-21 and Snail1 synthesis, Akt phosphorylation, NF-kappaB activation, and matrix metalloproteinase 2 (MMP2) synthesis and activation. Kallistatin via its heparin-binding site blocked TGF beta-induced miR-21, Snail1 expression, and ROS formation, as wild-type kallistatin, but not heparin-binding site mutant kallistatin, exerted the effect. Conversely, kallistatin through its active site stimulated the synthesis of endothelial nitric oxide synthase (eNOS), sirtuin 1 (Sirt1) and forkhead box O1 (FoxO1); however, these effects were blocked by genistein, a tyrosine kinase inhibitor. This is the first study to demonstrate that kallistatin's heparin binding site is crucial for preventing TGF-beta-induced miR-21 and oxidative stress, while its active site is key for stimulating the expression of antioxidant genes via interaction with an endothelial surface tyrosine kinase. These findings reveal novel mechanisms of kallistatin in protection against fibrosis and cancer by suppressing EndMT. PMID- 26156754 TI - Metabolic Syndrome and Osteoporosis in Relation to Muscle Mass. AB - This study aimed to examine the relationship between metabolic syndrome (MetS) and osteoporosis according to muscle mass levels and the joint relationship of MetS and muscle mass with osteoporosis in a representative population-based sample from the Korea National Health and Nutrition Examination Survey in 2010 2011. In 1654 men and 1979 women aged 50-93 years, body composition and bone mineral density at the femur and lumbar spine were measured using dual-energy X ray absorptiometry. Low- and high-muscle mass groups were identified using the mean sex-specific muscle mass of appendicular muscle mass/height(2). The covariates were age, health behaviors, serum 25-OH vitamin D and parathyroid hormone, calcium intake, and hormone replacement therapy for women. Men and women with MetS (defined by the Adult Treatment Panel III) had 43 and 31% lower odds for osteoporosis, respectively, compared with their MetS-free counterparts after adjusting for muscle mass and covariates. When stratified by muscle mass, MetS was not associated with osteoporosis in men, while associated in women with higher muscle mass (OR 0.65, 95% CI 0.46-0.91). Compared with MetS-free men and women with lower muscle mass, the odds for osteoporosis were 45% and 23, 52 and 15%, and 72 and 46% lower among those with low muscle mass and MetS, high muscle mass without MetS, and high muscle mass and MetS, respectively (P for trend <0.001). Combination of high muscle mass and MetS was associated with lower prevalence of osteoporosis in Korean men and women. PMID- 26156756 TI - A case of postoperative hepatic granuloma presumptively caused by surgical staples/clipping materials. AB - A 66-year-old man with postsigmoidectomy status for colon cancer received laparoscopic partial hepatectomy due to a hepatic mass with employing titanium clips were for a vascular clamp. Histological examination showed liver metastasis from sigmoid colon cancer. Twenty-nine months after the partial hepatectomy, a mass developed on the stump at the hepatic resection. Laparoscopic left lateral segmentectomy was conducted under suspicion of cancer recurrence and an automatic titanium stapling device was used. The macroscopically cut surface of the liver showed a grey-white solid nodule measuring 23 x 20 mm and involving metal clips. The nodule was consistent with granuloma microscopically. Twenty-three months after the segmentectomy, a mass reappeared on the hepatic radial margin and an open left lateral hepatic lobectomy was performed because of its growth tendency. Histopathological examination revealed granuloma similar to the previous instance. Since these nodules formed a granulomatous lesion surrounding metal staples/clips and evidence of caseous necrosis was lacking, granuloma due to surgical staples/clips was suspected. Sporadic case reports of postoperative pulmonary granuloma at the staple line have been published previously, but there are no articles detailing a case involving hepatic granuloma. We present our case as the first report of postoperative staple-line hepatic granuloma. PMID- 26156757 TI - Hannelore Wass: The Lasting Impact of a Death Educator, Scholar, Mentor, and Friend. AB - While there is no doubt that every individual's experiences with death and grief have a significant impact on his or her work as a death educator, scholar, or a clinician, it is a deeply personal choice whether or not one chooses to disclose those experiences to others thoughout one's career. Drawing upon memories of Dr. Hannelore Wass shared by colleagues, this article documents Wass's impact on the lives of thanatologists as a result of her talents as a scholar, death educator, and mentor as well as her friendship. PMID- 26156758 TI - Influence of Force Fields and Quantum Chemistry Approach on Spectral Densities of BChl a in Solution and in FMO Proteins. AB - Studies on light-harvesting (LH) systems have attracted much attention after the finding of long-lived quantum coherences in the exciton dynamics of the Fenna Matthews-Olson (FMO) complex. In this complex, excitation energy transfer occurs between the bacteriochlorophyll a (BChl a) pigments. Two quantum mechanics/molecular mechanics (QM/MM) studies, each with a different force-field and quantum chemistry approach, reported different excitation energy distributions for the FMO complex. To understand the reasons for these differences in the predicted excitation energies, we have carried out a comparative study between the simulations using the CHARMM and AMBER force field and the Zerner intermediate neglect of differential orbital (ZINDO)/S and time dependent density functional theory (TDDFT) quantum chemistry methods. The calculations using the CHARMM force field together with ZINDO/S or TDDFT always show a wider spread in the energy distribution compared to those using the AMBER force field. High- or low-energy tails in these energy distributions result in larger values for the spectral density at low frequencies. A detailed study on individual BChl a molecules in solution shows that without the environment, the density of states is the same for both force field sets. Including the environmental point charges, however, the excitation energy distribution gets broader and, depending on the applied methods, also asymmetric. The excitation energy distribution predicted using TDDFT together with the AMBER force field shows a symmetric, Gaussian-like distribution. PMID- 26156759 TI - Practical Considerations on the Multi-layer Mirrors for Superluminal Ring Laser Gyroscopes. AB - We have created a simple model to analyze the restrictions on superluminal ring laser gyroscopes arising from the absorption of coating materials. For a ring laser gyroscope with a cavity length of 15 cm, the scale factor enhancement is nearly impossible due to absorption from the high dispersion mirror. In order to obtain a practical superluminal ring laser gyroscope, the extinction coefficient of coating materials should be less than 1E-10, which is a challenge at present. PMID- 26156760 TI - Immunomodulatory effects of preparations from Anthroposophical Medicine for parenteral use. AB - BACKGROUND: Preparations from anthroposophical medicine (AM) are clinically used to treat inflammatory disorders. We wanted to investigate effects of a selection of AM medications for parenteral use in cell-based systems in vitro. METHODS: Colchicum officinale tuber D3, Mandragora D3, Rosmarinus officinale 5% and Bryophyllum 5% were selected for the experiments. Induction of apoptosis and necrosis (human lymphocytes and dendritic cells [DCs]) and proliferation of lymphocytes as well as maturation (expression of CD14, CD83 and CD86) and cytokine secretion (IL-10, IL12p70) of DCs were analyzed. Furthermore, proliferation of allogeneic human T lymphocytes was investigated in vitro in coculture experiments using mature DCs in comparison to controls. RESULTS: The respective preparations did not induce apoptosis or necrosis in lymphocytes or DCs. Lymphocyte proliferation was dose-dependently reduced by Colchicum officinale tuber D3 while the viability was unchanged. Rosmarinus officinale 5%, but not the other preparations, dose-dependently inhibited the maturation of immature DCs, reduced secretion of IL-10 and IL-12p70 and slightly inhibited proliferation of allogeneic CD4(+) T-lymphocytes in coculture experiments with DCs. CONCLUSION: The selected preparations from AM for parenteral use are nontoxic to lymphocytes and DCs. Rosmarinus officinale 5% has immunosuppressive properties on key functions of the immune system which propose further investigation. PMID- 26156761 TI - Environmental and scale-dependent evolutionary trends in the body size of crustaceans. AB - The ecological and physiological significance of body size is well recognized. However, key macroevolutionary questions regarding the dependency of body size trends on the taxonomic scale of analysis and the role of environment in controlling long-term evolution of body size are largely unknown. Here, we evaluate these issues for decapod crustaceans, a group that diversified in the Mesozoic. A compilation of body size data for 792 brachyuran crab and lobster species reveals that their maximum, mean and median body size increased, but no increase in minimum size was observed. This increase is not expressed within lineages, but is rather a product of the appearance and/or diversification of new clades of larger, primarily burrowing to shelter-seeking decapods. This argues against directional selective pressures within lineages. Rather, the trend is a macroevolutionary consequence of species sorting: preferential origination of new decapod clades with intrinsically larger body sizes. Furthermore, body size evolution appears to have been habitat-controlled. In the Cretaceous, reef associated crabs became markedly smaller than those in other habitats, a pattern that persists today. The long-term increase in body size of crabs and lobsters, coupled with their increased diversity and abundance, suggests that their ecological impact may have increased over evolutionary time. PMID- 26156763 TI - Population declines of tuna and relatives depend on their speed of life. AB - Larger-bodied species in a wide range of taxonomic groups including mammals, fishes and birds tend to decline more steeply and are at greater risk of extinction. Yet, the diversity in life histories is governed not only by body size, but also by time-related traits. A key question is whether this size dependency of vulnerability also holds, not just locally, but globally across a wider range of environments. We test the relative importance of size- and time related life-history traits and fishing mortality in determining population declines and current exploitation status in tunas and their relatives. We use high-quality datasets of half a century of population trajectories combined with population-level fishing mortalities and life-history traits. Time-related traits (e.g. growth rate), rather than size-related traits (e.g. maximum size), better explain the extent and rate of declines and current exploitation status across tuna assemblages, after controlling for fishing mortality. Consequently, there is strong geographical patterning in population declines, such that populations with slower life histories (found at higher cooler latitudes) have declined most and more steeply and have a higher probability of being overfished than populations with faster life histories (found at tropical latitudes). Hence, the strong, temperature-driven, latitudinal gradients in life-history traits may underlie the global patterning of population declines, fisheries collapses and local extinctions. PMID- 26156762 TI - Social setting, intuition and experience in laboratory experiments interact to shape cooperative decision-making. AB - Recent studies suggest that cooperative decision-making in one-shot interactions is a history-dependent dynamic process: promoting intuition versus deliberation typically has a positive effect on cooperation (dynamism) among people living in a cooperative setting and with no previous experience in economic games on cooperation (history dependence). Here, we report on a laboratory experiment exploring how these findings transfer to a non-cooperative setting. We find two major results: (i) promoting intuition versus deliberation has no effect on cooperative behaviour among inexperienced subjects living in a non-cooperative setting; (ii) experienced subjects cooperate more than inexperienced subjects, but only under time pressure. These results suggest that cooperation is a learning process, rather than an instinctive impulse or a self-controlled choice, and that experience operates primarily via the channel of intuition. Our findings shed further light on the cognitive basis of human cooperative decision-making and provide further support for the recently proposed social heuristics hypothesis. PMID- 26156764 TI - Evolution of protolinguistic abilities as a by-product of learning to forage in structured environments. AB - The skills required for the learning and use of language are the focus of extensive research, and their evolutionary origins are widely debated. Using agent-based simulations in a range of virtual environments, we demonstrate that challenges of foraging for food can select for cognitive mechanisms supporting complex, hierarchical, sequential learning, the need for which arises in language acquisition. Building on previous work, where we explored the conditions under which reinforcement learning is out-competed by seldom-reinforced continuous learning that constructs a network model of the environment, we now show that realistic features of the foraging environment can select for two critical advances: (i) chunking of meaningful sequences found in the data, leading to representations composed of units that better fit the prevalent statistical patterns in the environment; and (ii) generalization across units based on their contextual similarity. Importantly, these learning processes, which in our framework evolved for making better foraging decisions, had been earlier shown to reproduce a range of findings in language learning in humans. Thus, our results suggest a possible evolutionary trajectory that may have led from basic learning mechanisms to complex hierarchical sequential learning that can support advanced cognitive abilities of the kind needed for language acquisition. PMID- 26156765 TI - Indirect effects of parasitism: costs of infection to other individuals can be greater than direct costs borne by the host. AB - Parasitic infection has a direct physiological cost to hosts but may also alter how hosts interact with other individuals in their environment. Such indirect effects may alter both host fitness and the fitness of other individuals in the host's social network, yet the relative impact of direct and indirect effects of infection are rarely quantified. During reproduction, a host's social environment includes family members who may be in conflict over resource allocation. In such situations, infection may alter how resources are allocated, thereby redistributing the costs of parasitism between individuals. Here, we experimentally reduce parasite burdens of parent and/or nestling European shags (Phalacrocorax aristotelis) infected with Contracaecum nematodes in a factorial design, then simultaneously measure the impact of an individual's infection on all family members. We found no direct effect of infection on parent or offspring traits but indirect effects were detected in all group members, with both immediate effects (mass change and survival) and longer-term effects (timing of parents' subsequent breeding). Our results show that parasite infection can have a major impact on individuals other than the host, suggesting that the effect of parasites on population processes may be greater than previously thought. PMID- 26156766 TI - What you feel is what you see: inverse dynamics estimation underlies the resistive sensation of a delayed cursor. AB - How our central nervous system (CNS) learns and exploits relationships between force and motion is a fundamental issue in computational neuroscience. While several lines of evidence have suggested that the CNS predicts motion states and signals from motor commands for control and perception (forward dynamics), it remains controversial whether it also performs the 'inverse' computation, i.e. the estimation of force from motion (inverse dynamics). Here, we show that the resistive sensation we experience while moving a delayed cursor, perceived purely from the change in visual motion, provides evidence of the inverse computation. To clearly specify the computational process underlying the sensation, we systematically varied the visual feedback and examined its effect on the strength of the sensation. In contrast to the prevailing theory that sensory prediction errors modulate our perception, the sensation did not correlate with errors in cursor motion due to the delay. Instead, it correlated with the amount of exposure to the forward acceleration of the cursor. This indicates that the delayed cursor is interpreted as a mechanical load, and the sensation represents its visually implied reaction force. Namely, the CNS automatically computes inverse dynamics, using visually detected motions, to monitor the dynamic forces involved in our actions. PMID- 26156767 TI - delta-Conotoxin SuVIA suggests an evolutionary link between ancestral predator defence and the origin of fish-hunting behaviour in carnivorous cone snails. AB - Some venomous cone snails feed on small fishes using an immobilizing combination of synergistic venom peptides that target Kv and Nav channels. As part of this envenomation strategy, delta-conotoxins are potent ichtyotoxins that enhance Nav channel function. delta-Conotoxins belong to an ancient and widely distributed gene superfamily, but any evolutionary link from ancestral worm-eating cone snails to modern piscivorous species has not been elucidated. Here, we report the discovery of SuVIA, a potent vertebrate-active delta-conotoxin characterized from a vermivorous cone snail (Conus suturatus). SuVIA is equipotent at hNaV1.3, hNaV1.4 and hNaV1.6 with EC50s in the low nanomolar range. SuVIA also increased peak hNaV1.7 current by approximately 75% and shifted the voltage-dependence of activation to more hyperpolarized potentials from -15 mV to -25 mV, with little effect on the voltage-dependence of inactivation. Interestingly, the proximal venom gland expression and pain-inducing effect of SuVIA in mammals suggest that delta-conotoxins in vermivorous cone snails play a defensive role against higher order vertebrates. We propose that delta-conotoxins originally evolved in ancestral vermivorous cones to defend against larger predators including fishes have been repurposed to facilitate a shift to piscivorous behaviour, suggesting an unexpected underlying mechanism for this remarkable evolutionary transition. PMID- 26156768 TI - When and how did the terrestrial mid-Permian mass extinction occur? Evidence from the tetrapod record of the Karoo Basin, South Africa. AB - A mid-Permian (Guadalupian epoch) extinction event at approximately 260 Ma has been mooted for two decades. This is based primarily on invertebrate biostratigraphy of Guadalupian-Lopingian marine carbonate platforms in southern China, which are temporally constrained by correlation to the associated Emeishan Large Igneous Province (LIP). Despite attempts to identify a similar biodiversity crisis in the terrestrial realm, the low resolution of mid-Permian tetrapod biostratigraphy and a lack of robust geochronological constraints have until now hampered both the correlation and quantification of terrestrial extinctions. Here we present an extensive compilation of tetrapod-stratigraphic data analysed by the constrained optimization (CONOP) algorithm that reveals a significant extinction event among tetrapods within the lower Beaufort Group of the Karoo Basin, South Africa, in the latest Capitanian. Our fossil dataset reveals a 74 80% loss of generic richness between the upper Tapinocephalus Assemblage Zone (AZ) and the mid-Pristerognathus AZ that is temporally constrained by a U-Pb zircon date (CA-TIMS method) of 260.259 +/- 0.081 Ma from a tuff near the top of the Tapinocephalus AZ. This strengthens the biochronology of the Permian Beaufort Group and supports the existence of a mid-Permian mass extinction event on land near the end of the Guadalupian. Our results permit a temporal association between the extinction of dinocephalian therapsids and the LIP volcanism at Emeishan, as well as the marine end-Guadalupian extinctions. PMID- 26156769 TI - Agonistic reciprocity is associated with reduced male reproductive success within haremic social networks. AB - While individual variation in social behaviour is ubiquitous and causes social groups to differ in structure, how these structural differences affect fitness remains largely unknown. We used social network analysis of replicate bluebanded goby (Lythrypnus dalli) harems to identify the reproductive correlates of social network structure. In stable groups, we quantified agonistic behaviour, reproduction and steroid hormones, which can both affect and respond to social/reproductive cues. We identified distinct, optimal social structures associated with different reproductive measures. Male hatching success (HS) was negatively associated with agonistic reciprocity, a network structure that describes whether subordinates 'reciprocated' agonism received from dominants. Egg laying was associated with the individual network positions of the male and dominant female. Thus, males face a trade-off between promoting structures that facilitate egg laying versus HS. Whether this reproductive conflict is avoidable remains to be determined. We also identified different social and/or reproductive roles for 11-ketotestosterone, 17beta-oestradiol and cortisol, suggesting that specific neuroendocrine mechanisms may underlie connections between network structure and fitness. This is one of the first investigations of the reproductive and neuroendocrine correlates of social behaviour and network structure in replicate, naturalistic social groups and supports network structure as an important target for natural selection. PMID- 26156770 TI - Determination of growth stages and metabolic profiles in Brachypodium distachyon for comparison of developmental context with Triticeae crops. AB - Brachypodium distachyon is an emerging model plant for studying biological phenomena in temperate grasses. Study of the growth scale is essential to analyse spatio-temporal changes in molecular factors throughout the life cycle. For sensitive and robust staging based on morphology in B. distachyon, we demonstrated the utility of the BBCH (Biologische Bundesanstalt, Bundessortenamt and CHemical industry) scale, which is comparable to the Zadoks scale conventionally used for Triticeae crops. We compared the chronological progression of B. distachyon accessions Bd21 and Bd3-1, in addition to the progression of Chinese Spring wheat. The comparison of growth stages illustrates the morphological similarities and differences in the timing of life cycle events. Furthermore, we compared metabolite accumulation patterns across different growth stages and across different stress conditions using a widely targeted metabolome analysis. Metabolic profiling determined commonalities and specificities in chemical properties that were dependent on organisms, growth stages and/or stress conditions. Most metabolites accumulated equivalently in B. distachyon and wheat. This qualitative similarity indicated the superiority of B. distachyon as a model for Triticeae crops. The growth scale of B. distachyon should provide a conceptual framework for comparative analysis and for knowledge integration between this model grass and crops in the Pooideae subfamily. PMID- 26156771 TI - Sex differences in senescence: the role of intra-sexual competition in early adulthood. AB - Males and females frequently differ in their rates of ageing, but the origins of these differences are poorly understood. Sex differences in senescence have been hypothesized to arise, because investment in intra-sexual reproductive competition entails costs to somatic maintenance, leaving the sex that experiences stronger reproductive competition showing higher rates of senescence. However, evidence that sex differences in senescence are attributable to downstream effects of the intensity of intra-sexual reproductive competition experienced during the lifetime remains elusive. Here, we show using a 35 year study of wild European badgers (Meles meles), that (i) males show higher body mass senescence rates than females and (ii) this sex difference is largely attributable to sex-specific downstream effects of the intensity of intra-sexual competition experienced during early adulthood. Our findings provide rare support for the view that somatic maintenance costs arising from intra-sexual competition can cause both individual variation and sex differences in senescence. PMID- 26156772 TI - Does mixed-species flocking influence how birds respond to a gradient of land-use intensity? AB - Conservation biology is increasingly concerned with preserving interactions among species such as mutualisms in landscapes facing anthropogenic change. We investigated how one kind of mutualism, mixed-species bird flocks, influences the way in which birds respond to different habitat types of varying land-use intensity. We use data from a well-replicated, large-scale study in Sri Lanka and the Western Ghats of India, in which flocks were observed inside forest reserves, in 'buffer zones' of degraded forest or timber plantations, and in areas of intensive agriculture. We find flocks affected the responses of birds in three ways: (i) species with high propensity to flock were more sensitive to land use; (ii) different flock types, dominated by different flock leaders, varied in their sensitivity to land use and because following species have distinct preferences for leaders, this can have a cascading effect on followers' habitat selection; and (iii) those forest-interior species that remain outside of forests were found more inside flocks than would be expected by chance, as they may use flocks more in suboptimal habitat. We conclude that designing policies to protect flocks and their leading species may be an effective way to conserve multiple bird species in mixed forest and agricultural landscapes. PMID- 26156773 TI - Plant defences against ants provide a pathway to social parasitism in butterflies. AB - Understanding the chemical cues and gene expressions that mediate herbivore-host plant and parasite-host interactions can elucidate the ecological costs and benefits accruing to different partners in tight-knit community modules, and may reveal unexpected complexities. We investigated the exploitation of sequential hosts by the phytophagous-predaceous butterfly Maculinea arion, whose larvae initially feed on Origanum vulgare flowerheads before switching to parasitize Myrmica ant colonies for their main period of growth. Gravid female butterflies were attracted to Origanum plants that emitted high levels of the monoterpenoid volatile carvacrol, a condition that occurred when ants disturbed their roots: we also found that Origanum expressed four genes involved in monoterpene formation when ants were present, accompanied by a significant induction of jasmonates. When exposed to carvacrol, Myrmica workers upregulated five genes whose products bind and detoxify this biocide, and their colonies were more tolerant of it than other common ant genera, consistent with an observed ability to occupy the competitor-free spaces surrounding Origanum. A cost is potential colony destruction by Ma. arion, which in turn may benefit infested Origanum plants by relieving their roots of further damage. Our results suggest a new pathway, whereby social parasites can detect successive resources by employing plant volatiles to simultaneously select their initial plant food and a suitable sequential host. PMID- 26156774 TI - Diffusion tensor imaging of dolphin brains reveals direct auditory pathway to temporal lobe. AB - The brains of odontocetes (toothed whales) look grossly different from their terrestrial relatives. Because of their adaptation to the aquatic environment and their reliance on echolocation, the odontocetes' auditory system is both unique and crucial to their survival. Yet, scant data exist about the functional organization of the cetacean auditory system. A predominant hypothesis is that the primary auditory cortex lies in the suprasylvian gyrus along the vertex of the hemispheres, with this position induced by expansion of 'associative' regions in lateral and caudal directions. However, the precise location of the auditory cortex and its connections are still unknown. Here, we used a novel diffusion tensor imaging (DTI) sequence in archival post-mortem brains of a common dolphin (Delphinus delphis) and a pantropical dolphin (Stenella attenuata) to map their sensory and motor systems. Using thalamic parcellation based on traditionally defined regions for the primary visual (V1) and auditory cortex (A1), we found distinct regions of the thalamus connected to V1 and A1. But in addition to suprasylvian-A1, we report here, for the first time, the auditory cortex also exists in the temporal lobe, in a region near cetacean-A2 and possibly analogous to the primary auditory cortex in related terrestrial mammals (Artiodactyla). Using probabilistic tract tracing, we found a direct pathway from the inferior colliculus to the medial geniculate nucleus to the temporal lobe near the sylvian fissure. Our results demonstrate the feasibility of post-mortem DTI in archival specimens to answer basic questions in comparative neurobiology in a way that has not previously been possible and shows a link between the cetacean auditory system and those of terrestrial mammals. Given that fresh cetacean specimens are relatively rare, the ability to measure connectivity in archival specimens opens up a plethora of possibilities for investigating neuroanatomy in cetaceans and other species. PMID- 26156775 TI - Primary school education programmes can decrease child salt intake. PMID- 26156776 TI - Low-grade gliomas in children: single institutional experience in 198 cases. AB - INTRODUCTION: In pediatric population (0-18 years), low-grade gliomas (PLGG) are the most frequent brain tumors and majority are amenable for surgical removal. PATIENTS AND METHODS: A retrospective review of 198 children diagnosed with PLGG between 1980 and 2010 at HSJD was carried out. Several variables were studied to find prognostic factors related to the outcomes (progression-free survival (PFS) and overall survival (OS)). RESULTS: Median age at onset was 88.8 months (3.1 to 214.5 months, SD 53). Surgery was performed in 175 patients (88.4%), achieving gross total resection (GTR) in 77 (44%), subtotal resection (STR) in 87 (49.7%), and 11 (6.3%) biopsies. Pathological review classified 84 tumors as WHO grade I (48%) and 89 as grade II (50.8%). Adjuvant therapy (AT) was given to 75 patients (37.9%), radiotherapy in 24 (12.1%), chemotherapy in 33 (16.7%), and combined in 18 (9.1%). Sixteen patients (8.1%) died, 89 (43.4%) are alive with no evidence of disease, and 93 (47%) alive with disease, median follow-up 65.2 months. Outcome is significantly correlated with age (p = 0001, worse OS for patients younger than 12 months) and extent of tumor resection (p < 0001). OS for GTR/STR/biopsy was >200, 154.3, and 101.9 months, respectively. Patients treated with AT presented worse OS/PFS (p < 0.001) than those not treated. Histology was non significantly related to outcomes. CONCLUSION: In our series of PLGG, the best prognostic markers are tumor location (cerebellar) and the extent of tumor resection (GTR). Infants and patients who require adjuvant therapy because of tumor progression or recurrence have worse outcome. PMID- 26156777 TI - Histologically proven acute paediatric thoracic disc herniation causing paraparesis: a case report and review of literature. AB - PURPOSE: We describe an extremely rare and previously unreported presentation of acute progressive paraparesis secondary to traumatic thoracic disc herniation in a child presenting to our institution. METHODS: A 12-year-old girl presented with progressive paraparesis 24 h after falling from standing height while playing at school. She was being lifted up by her friends and fell landing on her feet then rolled onto her back initially with no pain or neurological sequelae. Over the next few hours, she developed back pain followed by progressive paraparesis associated with urinary retention and sensory impairment. RESULTS: MR imaging demonstrated an unusual lateral and dorsally based lesion at T7/8 causing cord compression which was thought to represent an epidural haematoma. Urgent posterior decompressive surgery was performed but no evidence of haematoma was seen, a large well-circumscribed solid piece of soft tissue was found in the extradural space causing significant cord compression. This was sent for histological analysis and subsequently reported as showing cartilaginous disc material. Postoperative MR imaging at 2 weeks and 3 months demonstrates complete resection of this disc material with no significant kyphotic deformity on standing X-ray at 18 months. Complete neurological recovery occurred over the subsequent 3 months following emergent surgery, and at 18-month review, the patient remains asymptomatic and fully independent. PMID- 26156778 TI - THE DEPTHS OF CELL MIGRATION. AB - A growing number of researchers are trying to tease out the cellular mechanisms of tumor metastasis. Sarah Webb examines the tools they are using to probe the mercurial movements of cancer cells. PMID- 26156779 TI - Comparison of plasma extracellular RNA isolation kits reveals kit-dependent biases. PMID- 26156780 TI - Surveying the repair of ancient DNA from bones via high-throughput sequencing. AB - DNA damage in the form of abasic sites, chemically altered nucleotides, and strand fragmentation is the foremost limitation in obtaining genetic information from many ancient samples. Upon cell death, DNA continues to endure various chemical attacks such as hydrolysis and oxidation, but repair pathways found in vivo no longer operate. By incubating degraded DNA with specific enzyme combinations adopted from these pathways, it is possible to reverse some of the post-mortem nucleic acid damage prior to downstream analyses such as library preparation, targeted enrichment, and high-throughput sequencing. Here, we evaluate the performance of two available repair protocols on previously characterized DNA extracts from four mammoths. Both methods use endonucleases and glycosylases along with a DNA polymerase-ligase combination. PreCR Repair Mix increases the number of molecules converted to sequencing libraries, leading to an increase in endogenous content and a decrease in cytosine-to-thymine transitions due to cytosine deamination. However, the effects of Nelson Repair Mix on repair of DNA damage remain inconclusive. PMID- 26156781 TI - MOTIFSIM: A web tool for detecting similarity in multiple DNA motif datasets. AB - Currently, there are a number of motif detection tools available that possess unique functionality. These tools often report different motifs, and therefore use of multiple tools is generally advised since common motifs reported by multiple tools are more likely to be biologically significant. However, results produced by these different tools need to be compared and existing similarity detection tools only allow comparison between two data sets. Here, we describe a motif similarity detection tool (MOTIFSIM) possessing a web-based, user-friendly interface that is capable of detecting similarity from multiple DNA motif data sets concurrently. Results can either be viewed online or downloaded. Users may also download and run MOTIFSIM as a command-line tool in stand-alone mode. The web tool, along with its command-line version, user manuals, and source codes, are freely available at http://biogrid-head.engr.uconn.edu/motifsim/. PMID- 26156782 TI - Rapid generation of secondary fibroblasts through teratoma formation. AB - The use of secondary or reprogrammable cells in the production of induced pluripotent stem cells (iPSCs) circumvents random infection by various viral particles and random, uncontrollable integrations of the viral genomes into different genomic loci. We have developed a convenient method for repeatedly producing genetically identical secondary fibroblasts via teratoma formation using pre-existing iPSCs. The iPSCs used in this study carried doxycycline (Dox) inducible transgenes for four transcription factors in their genome. Teratoma derived primary cells (TOFs) were obtained in a huge amount during the culture of teratomas and showed good ability to form iPSCs similar to that of regular secondary fibroblasts. Immunohistochemistry analysis demonstrated the potential of TOF-derived iPSCs to differentiate into all three germ layers. The gene expression profiles of these TOFs and their iPSCs closely mimicked those of regular embryonic fibroblasts and embryonic stem cells/iPSCs, respectively. The possibility that the iPSCs were derived from a small part of pluripotent cells lurking in the TOF population was precluded by the observation of doxycycline dependent and PluriSin (a compound selectively eliminating pluripotent cells)- independent formations of iPSCs. Our results showed that the TOFs retained the capability to mediate cellular reprogramming, similar to that of regular secondary fibroblasts. PMID- 26156783 TI - A method to simultaneously construct up to 12 differently sized Illumina Nextera long mate pair libraries with reduced DNA input, time, and cost. AB - Long mate pair (LMP) or "jump" libraries are invaluable for producing contiguous genome assemblies and assessing structural variation. However the consistent production of high quality (low duplication rate, accurately sized) LMP libraries has proven problematic in many genome projects. Input DNA length and quantity are key issues that can affect success. Here we demonstrate how 12 libraries covering a wide range of jump sizes can be constructed from <10 ug of DNA, thus ensuring production of the best LMP libraries from a given DNA sample. Finally, we demonstrate the accuracy of the insert sizes by mapping reads from each library back to an existing assembly. PMID- 26156784 TI - Reliability of two questionnaires on physical function in patients with stable coronary artery disease. AB - BACKGROUND: Exercise-based cardiac rehabilitation is highly recommended for patients with coronary artery disease, as it improves physical fitness and reduces mortality and morbidity. Physical fitness per se does not always correlate with the patient's physical function. For this reason, additional measurements of physical function could be included in cardiac rehabilitation programmes to further tailor interventions to suit the individual patient. As a result, reliable measurements to assess physical function are required for patients with coronary artery disease. AIM: The aim of this study was to evaluate the reliability of the Patient-Specific Functional Scale (PSFS) and the Disability Rating Index (DRI) in patients with stable coronary artery disease. MATERIAL: Fifty-one patients (11 women), age 63.9 (SD 7.6) years, with stable coronary artery disease and coronary-angiographic changes indicating an elective percutaneous coronary intervention, were recruited at the Cardiology Department at Sahlgrenska University Hospital, Gothenburg. METHODS: The reliability tests included stability over time, evaluated with a test-retest procedure using the intraclass correlation coefficient (ICC), and internal consistency, measured with Cronbach's alpha and item-total correlation coefficients. RESULTS: Both questionnaires were stable over time (DRI, ICC=0.74, and PSFS, ICC=0.72). The internal consistency for the DRI was good, with a Cronbach's alpha value of > 0.85 for all items. The item-total correlation coefficients presented acceptable values of > 0.40, apart from two items. CONCLUSION: We have provided introductory support for the reliability of the DRI and PSFS questionnaires in patients with stable CAD. These questionnaires can be used to assess physical function and to evaluate the effect of interventions in addition to measuring physical fitness. PMID- 26156785 TI - Increased intra- and extracellular granzyme expression in patients with tuberculosis. AB - Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. Granzymes (gzms) are proteases mainly found in cytotoxic lymphocytes, but also extracellularly. While the role of gzms in target cell death has been widely characterized, considerable evidence points towards broader roles related to infectious and inflammatory responses. To investigate the expression of the gzms in TB, intracellular gzms A, B and K were measured by flow cytometry in lymphocyte populations from peripheral blood mononuclear cells from 18 TB patients and 12 healthy donors from Bangladesh, and extracellular levels of gzmA and B were measured in serum from 58 TB patients and 31 healthy controls. TB patients showed increased expression of gzmA in CD8(+) T, CD4(+) T and CD56(+) T, but not NK, cells, and of gzmB in CD8(+) T cells, when compared to controls. GzmK expression was not altered in TB patients in any lymphocyte subset. The extracellular levels of gzmA and, to a lesser extent, of gzmB, were increased in TB patients, but did not correlate with intracellular gzm expression in lymphocyte subsets. Our results reveal enhanced intra- and extracellular expression of gzmA and B in patients with pulmonary TB, suggesting that gzms are part of the host response to tuberculosis. PMID- 26156786 TI - Magnetic patterning: local manipulation of the intergranular exchange coupling via grain boundary engineering. AB - Magnetic patterning, with designed spatial profile of the desired magnetic properties, has been a rising challenge for developing magnetic devices at nanoscale. Most existing methods rely on locally modifying magnetic anisotropy energy or saturation magnetization, and thus post stringent constraints on the adaptability in diverse applications. We propose an alternative route for magnetic patterning: by manipulating the local intergranular exchange coupling to tune lateral magnetic properties. As demonstration, the grain boundary structure of Co/Pt multilayers is engineered by thermal treatment, where the stress state of the multilayers and thus the intergranular exchange coupling can be modified. With Ag passivation layers on top of the Co/Pt multilayers, we can hinder the stress relaxation and grain boundary modification. Combining the pre-patterned Ag passivation layer with thermal treatment, we can design spatial variations of the magnetic properties by tuning the intergranular exchange coupling, which diversifies the magnetic patterning process and extends its feasibility for varieties of new devices. PMID- 26156787 TI - Perception of chasing in squirrel monkeys (Saimiri sciureus). AB - Understanding the intentions of others is crucial in developing positive social relationships. Comparative human and non-human animal studies have addressed the phylogenetic origin of this ability. However, few studies have explored the importance of motion information in distinguishing others' intentions and goals in non-human primates. This study addressed whether squirrel monkeys (Saimiri sciureus) are able to perceive a goal-directed motion pattern-specifically, chasing-represented by two geometric objects. In Experiment 1, we trained squirrel monkeys to discriminate a "Chasing" sequence from a "Random" sequence. We then confirmed that this discrimination transferred to new stimuli ("Chasing" and "Random") in a probe test. To determine whether the monkeys used similarities of trajectory to discriminate chasing from random motion, we also presented a non chasing "Clone" sequence in which the trajectories of the two figures were identical. Three of six monkeys were able to discriminate "Chasing" from the other sequences. In Experiment 2, we confirmed humans' recognition of chasing with the stimuli from Experiment 1. In Experiment 3, the three monkeys for which discrimination did not transfer to the new stimuli in Experiment 1 were trained to discriminate between "Chasing" and "Clone" sequences. At testing, all three monkeys had learned to discriminate chasing, and two transferred their learning to new stimuli. Our results suggest that squirrel monkeys use goal-directed motion patterns, rather than simply similarity of trajectory, to discriminate chasing. Further investigation is necessary to identify the motion characteristics that contribute to this discrimination. PMID- 26156788 TI - Evidence for the perceptual origin of right-sided feeding biases in cetaceans. AB - Foraging behaviour of many cetacean species features the side biases at the population level. The origin of these behavioural lateralisations remains generally unclear. Here we explored lateralisation in aerial display of resident orcas in different behavioural contexts. Side preferences were analysed in lunging during foraging and breaching. One event of each type of displays per individually identified orca was used for analysis. Orcas showed a population level preference to lunge on the right side when foraging (75% of lunges). In contrast, no lateralisation was found in breaching (54% of breaches to the right, 45% to the left). The right-sided bias in foraging found in orcas is in line with evidence from other whales, both baleen and toothed, and confirms the uniformity of feeding biases among cetaceans. In contrast to breaching, lunging in orcas was associated with fish pursuit, that is, with focused attention to and sensory perception of prey stimulus. The emergence of lateralisation in lunging and the absence of significant bias in breaching suggest that feeding biases in whales are underpinned by sensory lateralisation, that is, by lateralised hemispheric processing of sensory information about the prey. Evidence from orcas may be extrapolated to other cetaceans since right-sided biases in lunging during foraging is a very widespread phenomenon and likely to have a common origin. Our findings support the hypothesis that right-sided feeding biases are determined by left-hemisphere specialisation. PMID- 26156789 TI - Correction: An efficient phase-selective gelator for aromatic solvents recovery based on a cyanostilbene amide derivative. PMID- 26156790 TI - Perovskite Solar Cells with Near 100% Internal Quantum Efficiency Based on Large Single Crystalline Grains and Vertical Bulk Heterojunctions. AB - Imperfections in organometal halide perovskite films such as grain boundaries (GBs), defects, and traps detrimentally cause significant nonradiative recombination energy loss and decreased power conversion efficiency (PCE) in solar cells. Here, a simple layer-by-layer fabrication process based on air exposure followed by thermal annealing is reported to grow perovskite films with large, single-crystal grains and vertically oriented GBs. The hole-transport medium Spiro-OMeTAD is then infiltrated into the GBs to form vertically aligned bulk heterojunctions. Due to the space-charge regions in the vicinity of GBs, the nonradiative recombination in GBs is significantly suppressed. The GBs become active carrier collection channels. Thus, the internal quantum efficiencies of the devices approach 100% in the visible spectrum range. The optimized cells yield an average PCE of 16.3 +/- 0.9%, comparable to the best solution-processed perovskite devices, establishing them as important alternatives to growing ideal single crystal thin films in the pursuit toward theoretical maximum PCE with industrially realistic processing techniques. PMID- 26156792 TI - Prefrontal Cortex Vistas: A Serotonin Safari. PMID- 26156791 TI - Estrogens and Male Lower Urinary Tract Dysfunction. AB - Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology and affect the majority of men at some time during their lives. The development of BPH/LUTS is associated with an increased ratio of estrogen to androgen levels, and this ratio, when mimicked in a variety of animals, induces BPH and lower urinary tract dysfunction (LUTD). While the precise molecular etiology remains unclear, estrogens have been implicated in the development and maintenance of BPH. Numerous endogenous and exogenous estrogens exist in humans. These estrogens act via multiple estrogen receptors to promote or inhibit prostatic hyperplasia and other BPH-associated processes. The prostate is an estrogen target tissue, and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of estrogen action directly affecting prostate growth and differentiation in the context of BPH is an understudied area and remains to be elucidated. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation illustrating their potential roles in the development of BPH as therapy. More work will be required to identify estrogen signaling pathways associated with LUTD in order to develop more efficacious drugs for BPH treatment and prevention. PMID- 26156793 TI - Clinical and Electrocardiographic Characteristics of Electrical Storms Due to Monomorphic Ventricular Tachycardia Refractory to Intravenous Amiodarone. AB - BACKGROUND: Few reports are available on the characteristics of electrical storms of ventricular tachycardia (VT storm) refractory to intravenous (IV) amiodarone. METHODS AND RESULTS: IV-amiodarone was administered to 60 patients with ventricular tachyarrhythmia between 2007 and 2012. VT storms, defined as 3 or more episodes of VT within 24 h, occurred in 30 patients (68+/-12 years, 7 female), with 12 having ischemic and 18 non-ischemic heart disease. We compared the clinical and electrocardiographic characteristics of the patients with VT storms suppressed by IV-amiodarone (Effective group) to those of patients not affected by the treatment (Refractory group). IV-amiodarone could not control recurrence of VT in 9 patients (30%). The Refractory group comprised 5 patients with acute myocardial infarctions. Although there was no difference in the VT cycle length, the QRS duration of both the VT and premature ventricular contractions (PVCs) followed by VT was narrower in the Refractory group than in the Effective group (140+/-30 vs. 178+/-25 ms, P<0.01; 121+/-14 vs. 179+/-22 ms, P<0.01). In the Refractory group, additional administration of IV-mexiletine and/or Purkinje potential-guided catheter ablation was effective. CONCLUSIONS: IV amiodarone-refractory VT exhibited a relatively narrow QRS tachycardia. The narrow triggering PVCs, suggesting a Purkinje fiber origin, may be treated by additional IV-mexiletine and endocardial catheter ablation. PMID- 26156794 TI - Overview of the 79th Annual Scientific Meeting of the Japanese Circulation Society - Late-Breaking Cardiovascular Medicine From Japan. AB - The 79th Annual Scientific Meeting of the Japanese Circulation Society was held in Osaka on April 24-26, 2015. The main theme was "Late-breaking Cardiovascular Medicine from Japan". Recently, optimal medical treatment has been guided by evidence-based medicine. We aim to emphasize the research findings and advances in cardiology from Japan, in the hope that Japan will become one of the leaders in the field worldwide. Unlike previous meetings, this annual scientific meeting was held in late April. Approximately 18,000 people, including medical doctors, healthcare professionals, and management staff, attended. The meeting was successfully completed, and included discussions on state-of-the art medicine. PMID- 26156795 TI - The effect of confinement on the crystalline microstructure of polymer : fullerene bulk heterojunctions. AB - We investigate the effect of confinement on the crystalline microstructure of the polymer component of polymer : fullerene bulk heterojunction thin films using grazing incidence wide angle X-ray scattering. We find that the polymer crystallite size decreases and the alignment of the molecules along the surface normal increases, as the thin-film thickness is reduced from 920 nm to <20 nm and approaches the thin-film confinement regime. Furthermore, we find that the polymer crystallite size near the surface (air interface) is lower than the crystallite size in the bulk or the bottom (substrate interface) of bulk heterojunction films thicker than the confinement regime. Variation in polymer crystallite size can cause changes in charge carrier mobility and recombination rates, which in turn affect the performance of bulk heterojunction thin film devices such as photovoltaics and photodetectors. PMID- 26156796 TI - Hepatic Uptake of Rectally Administered Butyrate Prevents an Increase in Systemic Butyrate Concentrations in Humans. AB - BACKGROUND: Short-chain fatty acids (SCFAs), fermentation products of undigested fibers, are considered beneficial for colonic health. High plasma concentrations are potentially harmful; therefore, information about systemic SCFA clearance is needed before therapeutic use of prebiotics or colonic SCFA administration. OBJECTIVE: The aim of this study was to investigate the effect of rectal butyrate administration on SCFA interorgan exchange. METHODS: Twelve patients (7 men; age: 66.4 +/- 2.0 y; BMI 24.5 +/- 1.4 kg/m(2)) undergoing upper abdominal surgery participated in this randomized placebo-controlled trial. During surgery, 1 group received a butyrate enema (100 mmol sodium butyrate/L; 60 mL; n = 7), and the other group a placebo (140 mmol 0.9% NaCl/L; 60 mL; n = 5). Before and 5, 15, and 30 min after administration, blood samples were taken from the radial artery, hepatic vein, and portal vein. Plasma SCFA concentrations were analyzed, and fluxes from portal-drained viscera, liver, and splanchnic area were calculated and used for the calculation of the incremental area under the curve (iAUC) over a 30-min period. RESULTS: Rectal butyrate administration led to higher portal butyrate concentrations at 5 min compared with placebo (92.2 +/- 27.0 MUmol/L vs. 14.3 +/- 3.4 MUmol/L, respectively; P < 0.01). In the butyrate-treated group, iAUCs of gut release (282.8 +/- 133.8 MUmol/kg BW . 0.5 h) and liver uptake ( 293.7 +/- 136.0 MUmol/kg BW . 0.5 h) of butyrate were greater than in the placebo group [-16.6 +/- 13.4 MUmol/kg BW . 0.5 h (gut release) and 16.0 +/- 13.8 MUmol/kg BW . 0.5 h (liver uptake); P = 0.01 and P < 0.05, respectively]. As a result, splanchnic butyrate release did not differ between groups. CONCLUSION: After colonic butyrate administration, splanchnic butyrate release was prevented in patients undergoing upper abdominal surgery. These observations imply that therapeutic colonic SCFA administration at this dose is safe. The trial was registered at clinicaltrials.gov as NCT02271802. PMID- 26156798 TI - Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. AB - Autophagosome-lysosome fusion and autolysosome acidification constitute late steps in the autophagic process necessary to maintain functional autophagic flux and cellular homeostasis. Both of these steps are disrupted by the V-ATPase inhibitor bafilomycin A1, but the mechanisms potentially linking them are unclear. We recently revisited the role of lysosomal acidification in autophagosome-lysosome fusion, using an in vivo approach in Drosophila. By genetically depleting individual subunits of the V-ATPase, we confirmed its role in lysosomal acidification and autophagic cargo degradation. Surprisingly, vesicle fusion remained active in V-ATPase-depleted cells, indicating that autophagosome-lysosome fusion and autolysosome acidification are 2 separable processes. In contrast, bafilomycin A1 inhibited both acidification and fusion, consistent with its effects in mammalian cells. Together, these results imply that this drug inhibits fusion independently of its effect on V-ATPase-mediated acidification. We identified the ER-calcium ATPase Ca-P60A/dSERCA as a novel target of bafilomycin A1. Autophagosome-lysosome fusion was defective in Ca P60A/dSERCA-depleted cells, and bafilomycin A1 induced a significant increase in cytosolic calcium concentration and disrupted Ca-P60A/SERCA-mediated fusion. Thus, bafilomycin A1 disrupts autophagic flux by independently inhibiting V ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. PMID- 26156799 TI - Knockdown of PLCepsilon inhibits inflammatory cytokine release via STAT3 phosphorylation in human bladder cancer cells. AB - Phospholipase Cepsilon (PLCepsilon) is a multifunctional enzyme implicated in inflammatory functions. There are limited data, however, on how PLCepsilon can alter inflammatory cytokine by affecting downstream pathways. Recent studies suggest that inflammation is likely to have an important role in transitional cell carcinoma of bladder (TCCB) and cancer disease progression. Here, we showed that PLCepsilon and p-STAT3 expression were both elevated in TCCB tissues compared to adjacent tissues, and the increase of PLCepsilon level was associated with the increase of p-STAT3 level. Then, knockdown of PLCepsilon using adenovirus-shPLCepsilon significantly decreased inflammatory cytokine (IL-6, TNF alpha, IL-1beta) expression and inflammation-associated gene (TLR4, MyD88, p STAT3) expression. Furthermore, we demonstrated that PLCepsilon knockdown blocked LPS-induced inflammatory cytokine and p-STAT3 expression. Additionally, we found that combined treatment of STAT3 inhibitor S3I-201 with adenovirus-shPLCepsilon exhibited synergistic inhibitory effects on expression of p-STAT3. Our results suggested that STAT3 phosphorylation is involved in PLCepsilon-mediated inflammatory cytokine release. Our research is of potential importance in drug development programs using PLCepsilon as a therapeutic target for TCCB. PMID- 26156797 TI - Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women. AB - BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present ( 18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736. PMID- 26156800 TI - Astrocyte-elevated gene-1 mediates insulin-like growth factor 1-induced the progression of cardiac myxoma. AB - Recently, astrocyte-elevated gene-1 (AEG-1) and insulin-like growth factor 1 (IGF 1) have been involved in the regulation of multiple signaling pathways in tumorigenesis. To date, the detailed mechanisms underlying IGF-1-AEG-1 pathway induced proliferation and apoptosis in cardiac myxoma (CM) was not reported. In the present study, we used immnohistochemistry, immunoblotting, and qRT-PCR to detect the expression profile of IGF-1 and AEG-1 in 90 CM tissues, and then cultured CM cells were subjected to si-AEG-1, in vitro, and in vivo assays. Our findings showed that IGF-1 and AEG-1 were obviously upregulated in CM tissues and markedly associated with tumor size. When CM cells were treated with si-AEG-1, si AEG-1 attenuated IGF-1-induced CM cell growth and enhanced cell apoptosis. Mechanically, we validated the expression of AEG-1, p-Erk1/2, and p-Akt increased in CM cells in response to IGF-1 treatment in a time-dependent manner. However, si-AEG-1 affected the expression of these proteins. Functionally, we found the knockdown of AEG-1-inhibited G1/S transition and tumor formation of CM cells. In conclusion, AEG-1 regulates IGF-1-induced proliferation and apoptosis via Erk1/2 and Akt signaling in CM development, which suggests IGF-1-AEG-1 signaling could be recommended to be a useful target to exert anti-tumor effects on CM. PMID- 26156801 TI - High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders. AB - Many cell types release extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic bodies, which play a role in physiology and diseases. Presence and phenotype of circulating EVs in hematological malignancies (HMs) remain largely unexplored.The aim of this study was to characterize EVs in peripheral blood of HM patients compared to healthy subjects (controls). We isolated serum EVs from patients with chronic lymphocytic leukemia (CLL), non Hodgkin's lymphoma (NHL), Waldenstrom's macroglobulinemia (WM), Hodgkin's lymphoma (HL), multiple myeloma (MM), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and controls. EVs were isolated from serum of peripheral blood by ultracentrifuge steps and analyzed by flow cytometry to define count, size, and immunophenotype. MV levels were significantly elevated in WM, HL, MM, AML, and some MPNs and, though at a lesser degree, in CLL and NHL as compared to healthy controls. HL, MM, and MPNs generated a population of MVs characterized by lower size (below 0.3 MUm) when compared to controls. MVs from patients specifically expressed tumor related antigens, such as CD19 in B cell neoplasms, CD38 in MM, CD13 in myeloid tumors, and CD30 in HL. Both total and antigen-specific count of MVs significantly correlated with different HM clinical features such as Rai stage in CLL, International Prognostic Scoring System in WM, International Staging System in MM, and clinical stage in HL. MVs may represent a novel biomarker in HMs. PMID- 26156803 TI - MicroRNA-133a functions as a tumor suppressor by targeting IGF-1R in hepatocellular carcinoma. AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs and have critical roles in tumorigenesis and metastasis. A growing body of evidence showed that microRNA 133a (miR-133a) was downregulated and played tumor suppressor roles in gastric, colorectal, bladder, and lung cancer. However, the role and underlying molecular mechanism of miR-133a in hepatocellular carcinoma (HCC) remain unclear. In this study, we analyzed the expression of miR-133a in HCC tissues and HCC cell lines. We find that miR-133a was downregulated in HCC tissues and cell lines and that miR-133a expression negatively correlated with tumor differentiation (P < 0.01), TNM stage (P < 0.01), and lymph node metastasis (P < 0.01). Then, functional studies demonstrate that restoration of miR-133a in HepG2 cells significantly suppressed proliferation, colony formation, migration, and invasion, induced cell cycle arrest at G0/G1 stage and cell apoptosis in vitro, and decreased tumor size and weight in a nude mouse HepG2 xenograft model. Using bioinformatics method and dual luciferase assays identified insulin-like growth factor 1 receptor (IGF-1R) as a direct target of miR-133a in HCC cells. Furthermore, overexpression of miR 133a inhibited activation AKT and ERK signal pathway, which contributed to suppression of HCC cell growth. These findings suggest that miR-133a may act as a tumor suppressor and inhibited survival of HCC cells by targeting IGF-1R. PMID- 26156802 TI - The effect of recombinant lentiviral vector encoding miR-145 on human esophageal cancer cells. AB - miR-145, a newly identified microRNA molecule, is hypothesized to function as a tumor suppressor, but this activity has not been investigated in esophageal l carcinoma (EC). The aim of this study was to investigate the effect of miR-145 on the biological features of EC cells. miR-145 was obtained using PCR technology and cloned into the lentiviral vector, pLVX-IRES-ZsGreen1, to construct the resulting vector, pLVX-IZ-miR-145. The vector was packaged, the viral titer was tested, and ECA109 cells were infected with the optimal viral titer. Cells that were stably transfected with miR-145 were screened. Flow cytometry was used to analyze enhanced green fluorescence protein gene expression, and to measure cell apoptosis and cell cycle. miR-145 expression was detected by real-time fluorescent quantitative PCR. Furthermore, cell proliferation was assayed using CCK-8 assay. The pLVX-IZ-miR-145 vector was successfully constructed, and the viral titer achieved up to 5.0 * 10(8) TU/mL. The transfection efficiency was 90 %. Compared to the control group, the expression level of miR-145 in the transfected group was significantly higher (185-fold, P < 0.05). miR-145 overexpression significantly inhibited esophageal cancer cell proliferation (P < 0.05). Moreover, the number of cells at the G2/M stage, as well as the cell apoptotic rate, in the miR-145-transfected group was significantly increased (P < 0.05). Our study reveals that overexpression of miR-145 inhibits cell proliferation, increases apoptosis, and influences the cell cycle progression of EC cell. PMID- 26156804 TI - Speckle-type POZ protein is negatively associated with malignancies and inhibits cell proliferation and migration in liver cancer. AB - Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor that is frequently mutated in human cancers. Our previous findings have indicated that SPOP is mutated and functions as a novel tumor suppressor in hepatoblastoma (HB). However, the biological roles and clinical significance of this SPOP in hepatocellular carcinoma (HCC) remain unknown. In this study, we found that the expression level of SPOP was downregulated in HCC primary tumors by quantitative real-time PCR and the protein level of SPOP was also reduced in 72 pairs of HCC tissue microarrays by immunohistochemical analyses. Moreover, SPOP expression was observed to negatively correlate with the tumor grade and intrahepatic metastasis of HCC patients. Furthermore, we revealed that SPOP not only inhibits cell proliferation but also inhibits the motility of liver cancer cells. Finally, we discovered that one of the mechanisms through which SPOP inhibits liver cancer cell migration involves the disruption of ZEB2 expression and the associated epithelial-mesenchymal transition program. Together, our findings emphasize the critical role of SPOP in the regulation of proliferation and migration in liver cancer. PMID- 26156805 TI - The key role of astrocyte elevated gene-1 in CCR6-induced EMT in cervical cancer. AB - In recent years, astrocyte elevated gene-1 (AEG-1) has been recommended as an important mediator that is involved in the epithelial-to-mesenchymal transition (EMT) process. However, the mechanisms underlying the chemokine (C-C motif) ligand 20 (CCL20)/chemokine (C-C motif) receptor 6 (CCR6)-AEG-1 pathway-mediated EMT in cervical cancer (CC) have not been well featured till now. We used immunohistochemistry and immunoblotting to assess the expression of AEG-1 in 94 cervical cancer tissues and cells. Subsequently, cervical cancer SiHa cells were treated with si-AEG-1 and then subjected to in vitro assays. We observed that AEG 1 proteins were highly expressed in cervical cancer tissues and closely correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and metastasis. Importantly, we validated the expression of AEG-1, p Erk1/2, p-Akt, vimentin, N-cadherin, and matrix metalloproteinase 2 (MMP2) increased in SiHa with CCL20 treatment in a concentration-dependent manner. When cells were treated with si-AEG-1, the expression of p-Erk1/2, p-Akt, vimentin, N cadherin, and MMP2 was also downregulated. Using the cell cycle assay, the knockdown of AEG-1 inhibited the entry of G1 into S phase. In conclusion, AEG-1 mediates CCL20/CCR6-induced EMT development via both Erk1/2 and Akt signaling pathway in cervical cancer, which indicates that CCL20/CCR6-AEG-1-EMT pathway could be suggested as a useful target to affect the progression of cervical cancer. PMID- 26156808 TI - Real-time imaging of anti-biofilm effects using CP-OCT. AB - The objective of this study was to develop a method to reliably and reproducibly assess the physical properties of in vitro multi-species plaque derived biofilms. A custom flow cell (FC) was designed to model oral cavity shear stresses on biofilms grown on hydroxyapatite (HA) discs. A finite-element program (ANSYS 13) modeled flow velocities and wall shear stresses on the interior 3D dimensions. For the experiment, 1% chlorhexidine (CHX), 5 M urea, and a 1* phosphate-buffered saline (PBS) were flown through the FC simulating oral rinsing. Near infrared cross-polarization optical coherence tomography (CP-OCT) non-destructively imaged the fluid immersed biofilms in real time (20 frames/s). During low flow, the swell of the biofilm caused from 5 M urea was quite pronounced increase in vertical dimension. Biofilms exposed to 1% CHX showed a slight collapse in the vertical dimension of the biofilm during low flow. During high flow/high sheer stress, the 5 M urea solution effectively removed the biofilm, while both 1% CHX and 1* PBS did not remove biofilms even under high velocity/shear stress conditions. PMID- 26156806 TI - Physiological and molecular responses to an acute bout of reduced-exertion high intensity interval training (REHIT). AB - PURPOSE: We have previously shown that 6 weeks of reduced-exertion high-intensity interval training (REHIT) improves VO2max in sedentary men and women and insulin sensitivity in men. Here, we present two studies examining the acute physiological and molecular responses to REHIT. METHODS: In Study 1, five men and six women (age: 26 +/- 7 year, BMI: 23 +/- 3 kg m(-2), VO2max: 51 +/- 11 ml kg( 1) min(-1)) performed a single 10-min REHIT cycling session (60 W and two 20-s 'all-out' sprints), with vastus lateralis biopsies taken before and 0, 30, and 180 min post-exercise for analysis of glycogen content, phosphorylation of AMPK, p38 MAPK and ACC, and gene expression of PGC1alpha and GLUT4. In Study 2, eight men (21 +/- 2 year; 25 +/- 4 kg.m(-2); 39 +/- 10 ml kg(-1) min(-1)) performed three trials (REHIT, 30-min cycling at 50 % of VO2max, and a resting control condition) in a randomised cross-over design. Expired air, venous blood samples, and subjective measures of appetite and fatigue were collected before and 0, 15, 30, and 90 min post-exercise. RESULTS: Acutely, REHIT was associated with a decrease in muscle glycogen, increased ACC phosphorylation, and activation of PGC1alpha. When compared to aerobic exercise, changes in VO2, RER, plasma volume, and plasma lactate and ghrelin were significantly more pronounced with REHIT, whereas plasma glucose, NEFAs, PYY, and measures of appetite were unaffected. CONCLUSIONS: Collectively, these data demonstrate that REHIT is associated with a pronounced disturbance of physiological homeostasis and associated activation of signalling pathways, which together may help explain previously observed adaptations once considered exclusive to aerobic exercise. PMID- 26156809 TI - How many foods in the UK carry health and nutrition claims, and are they healthier than those that do not? AB - OBJECTIVE: The present study aimed to measure the prevalence of different types of health and nutrition claims on foods and non-alcoholic beverages in a UK sample and to assess the nutritional quality of such products carrying health or nutrition claims. DESIGN: A survey of health and nutrition claims on food packaging using a newly defined taxonomy of claims and internationally agreed definitions of claim types. SETTING: A national UK food retailer: Tesco. SUBJECTS: Three hundred and eighty-two products randomly sampled from those available through the retailer's website. RESULTS: Of the products, 32 % (95 % CI 28, 37 %) carried either a health or nutrition claim; 15 % (95 % CI 11, 18 %) of products carried at least one health claim and 29 % (95 % CI 25, 34 %) carried at least one nutrition claim. When adjusted for product category, products carrying health claims tended to be lower in total fat and saturated fat than those that did not, but there was no significant difference in sugar or sodium levels. Products carrying health claims had slightly higher fibre levels than products without. Results were similar for comparisons between products that carry nutrition claims and those that do not. CONCLUSIONS: Health and nutrition claims appear frequently on food and beverage products in the UK. The nutrient profile of products carrying claims is marginally healthier than for similar products without claims, suggesting that claims may have some but limited informational value. The implication of these findings for guiding policy is unclear; future research should investigate the 'clinical relevance' of these differences in nutritional quality. PMID- 26156810 TI - Methyl-CpG-Binding Protein 2 (MECP2) Polymorphism in Iranian Patients with Systemic Lupus Erythematosus. AB - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which involves many organs and presents with various symptoms. It has been shown that genetic and environmental factors play a major role in this disease and may affect the onset, activity, damage, and mortality of the disease. According to recent studies, methyl-CpG-binding protein 2 (MECP2) has been associated with SLE in various populations. Herein, we studied MECP2 polymorphism in Iranian lupus patients and controls. The study included a total of 884 samples of Iranian ancestry (492 independent SLE patients and 392 unrelated healthy controls). Healthy controls were gender-, ethnic-, and age-matched with the patients. Patient and control samples were genotyped for rs1734787, rs1734791, rs1734792, and rs17435 by applying the Allelic Discrimination Real-Time PCR System. Our results showed a significant association between rs1734787 and rs1734791 SNPs and the risk of SLE in the Iranian population (p = 0.028, p = 0.028), but did not show any significant association with rs1734792 and rs17435 SNPs (p = 075, p = 0.75). The rs1734787 C and the rs1734791 T allele frequencies in the patients were significantly higher than the control group (p = 0.014, p = 0.012). In addition, a significant CTAT haplotype frequency was observed in cases with SLE (p = 0.012), and a significant AAAT haplotype frequency was observed in the control group (p = 0.0003). However, there was no significant association between genotype frequencies and SLE patients. Also, there was no significant association between these SNPs and clinical features. The result of this study suggests that polymorphism in the MECP2 locus is associated with the susceptibility of Iranian SLE patients. PMID- 26156811 TI - Thymoquinone Inhibits IL-1beta-Induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing NF-kappaB and MAPKs Signaling Pathway. AB - Thymoquinone, an active ingredient isolated from Nigella sativa, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effect of thymoquinone on IL-1beta-stimulated osteoarthritis chondrocytes remains unclear. In this study, we designed to investigate the anti-inflammatory effects and elucidated the underlying mechanism of thymoquinone on IL-1beta-stimulated human osteoarthritis chondrocytes. The effects of thymoquinone on inflammatory mediators COX-2, iNOS, NO, PGE2, as well as MMP-1, MMP3, MMP13 production were detected. The results demonstrated that thymoquinone concentration-dependently inhibited IL-1beta-induced COX-2, iNOS, NO, and PGE2 production. Thymoquinone also suppressed IL-1beta-induced MMP-1, MMP3, and MMP13 production. We found that thymoquinone significantly inhibited IL-1beta-induced NF-kappaB activation and IkappaBalpha degradation. In addition, thymoquinone was found to suppress IL 1beta-induced mitogen-activated protein kinases (MAPKs) activation. In conclusion, thymoquinone inhibited IL-1beta-induced inflammatory mediator production by inhibition of NF-kappaB and MAPKs signaling pathways in osteoarthritis chondrocytes. Thymoquinone may be a potential agent in the treatment of osteoarthritis. PMID- 26156812 TI - Calcitriol Suppressed Inflammatory Reactions in IL-1beta-Stimulated Human Periodontal Ligament Cells. AB - Vitamin D has important roles on control of calcium and phosphate levels in the body. However, the role of vitamin D on the pathogenesis of periodontal disease is still uncertain. Therefore, we examined the effect of the hormonal form of vitamin D, calcitriol, on inflammatory responses of human periodontal ligament cells (HPDLC). We detected vitamin D receptor expression in non-stimulated HPDLC. Calcitriol inhibited interleukin (IL)-6, IL-8, CC chemokine ligand (CCL) 20, CXC chemokine ligand (CXCL) 10, and matrix metalloproteinase (MMP)-3 release from IL 1beta-stimulated HPDLC. Tissue inhibitor of metalloproteinase (TIMP)-1 production did not change by calcitriol. Moreover, we found c-jun N-terminal kinase (JNK) phosphorylation and IkappaB-alpha degradation in IL-1beta-stimulated HPDLC were inhibited by calcitriol, and JNK and nuclear factor (NF)-kappaB inhibitors could decrease IL-6, IL-8, CCL20, CXCL10, and MMP-3 productions in IL-1beta-treated HPDLC. These findings suggest that vitamin D could modulate inflammatory response in periodontal tissues. PMID- 26156814 TI - [Where are we going? The forced deinstitutionalization is a double-edged sword]. AB - In Italy the deep crisis of the judicial system, and in particular of the jail system, has allowed the development of an intense deinstitutionalization. A set of rules implemented since 2008 are leading to the closure of the Judicial Psychiatric Hospitals and, simultaneously, to the release of a large number of detainees, mainly restricted for drug offenses. There is a lack of effective structures for the management of this population, plagued with mental disorders. Social policies are needed that allow the development of structures for this complex population, which otherwise will be left to itself. PMID- 26156815 TI - [How do we treat the broad spectrum of patients with serious mental illness who have committed crimes? The Law 81/2014: limits and problems]. AB - In Italy an ongoing process of deinstitutionalization unprecedented in the world is been enacted. The Judicial Psychiatric Hospitals, that were never reformed in the past 80 years, are now on the edge of their closure. This process is being implemented through a layering of rules that had no purpose other than the rapid closure of these structures. The Mental Health Departments have now the responsibility of a multiplicity of new and highly specialized tasks, and an extension of their power to control. There is no previous organization for these tasks in the Mental Health System. Some of the recently enacted laws, such as the Law 81 of 2014, are intented to solve some problems, althought issues of deinstitutionalization are getting worse. In our opinion several management aspects of this population of severe psychiatric patients are unfit with the present organization of the Mental Health Services. There is need for legislative action coordinated and based on a long-term perspective. PMID- 26156816 TI - [Cognitive deficits in depressive illness: how many and which instruments to identify them?]. AB - INTRODUCTION: Major depressive disorder is a disabling illness that involves affect and cognition of a person, negatively influencing social and work functioning. Cognitive deficits are often present in depression, although they are often believed to be secondary to typical depressive symptoms. AIM: A detailed literature review has been carried out to assess the cognitive deficits identified in people with major depressive disorder and identify specific assessment tools used for their evaluation. METHODS: Using key-words, we selected papers published on Embase and PubMed/Medline, with a particular reference to those published in the last five years. RESULTS: The literature review confirmed that cognitive deficits are one of the most important causes of social disfunctioning in patients with major depressive disorder. Cognitive deficits can be observed already in the first depressive episode. Assessment tools for cognitive deficits are scarcely used in clinical practice. CONCLUSION: There is a need to identify cognitive deficits in people with major depressive disorder and their relation with social and work functioning, quality of life and risk of relapse as well as to assess the effects of therapeutic intervention on cognitive performance. To achieve this purpose, it is important to use appropriate and sensitive tools for the assessment of cognitive deficits. PMID- 26156817 TI - [Antidepressant use in pregnancy: a critical review of the risk and benefits]. AB - AIM: Pregnancy is considered a high-risk period for the development of a depressive disorder in women, particularly in those with a pre-existing affective disorder. The use of antidepressants in pregnancy may be responsible for congenital malformations and neonatal toxicity. The aim of the study is to review the literature examining the various antidepressants used in pregnancy and their relationship with the development of congenital malformation and neonatal diseases; in particular, we have focused on the evaluation of the risk/benefit in the administration of specific drugs, the possible teratogenicity and placental transfer. MATERIALS AND METHODS: We performed a computerized search of PubMed through the papers published from 1996 to 2014, identifying the studies that have showed a relationship between treatment with antidepressants in pregnancy and teratogenic effects and toxicity in the short and long term. RESULTS: The revision of the pharmacovigilance studies indicate that most of the selective serotonin reuptake inhibitors have a teratogenic risk substantially similar to that of unexposed controls. For other antidepressants (tricyclics, mirtazapine, venlafaxine, escitalopram, duloxetine) the evidences on the level of risk are still numerically inconsistent and need to be clarified by further research. CONCLUSIONS: Despite the lack of guidelines for the treatment of depressive disorders during pregnancy, clinically relevant data are continuing to accumulate in the literature. For many medications, compared to the past, we are now able to make a more rational and less approximate estimate of the risk/benefit ratio. PMID- 26156818 TI - [Timing and effectiveness of Brenner's IPT cognitive training in early psychosis. A pilot study]. AB - AIM: The present study evaluates the outcome of cognitive training as part of Brenner's Integrated Psychological Therapy (IPT) in two groups of individuals with a schizophrenic spectrum disorder (F20-F24 ICD-10). 28 participants were divided into either an experimental group or a control group. The experimental group was composed of 13 individuals (46%) with a mean age of 21.2 years and a mean duration of illness (since their first episode of psychosis FEP) of 15.6 months. The control group included 15 individuals (54%) with a mean age of 25.6 years and a mean duration of illness of 74.4 months (beyond the critical period). METHOD: Participants underwent an assessment of cognitive functioning which focused on attention, memory, executive functioning and cognitive flexibility as measured by the WCST (Wisconsin Card Sorting Test). Each individual was tested pre- and 6-month post-intervention. The original IPT method was altered by reducing the frequency of sessions to once a week and by limiting our sessions to 2-3 individuals per group. RESULTS: Cognitive flexibility (p<0.01) and long-term memory (p<0.01) improved only in the experimental group. These former skills worsened in the control group (p<0.01). Selective attention, short-term memory and verbal fluency improved in both groups (from p<0.05 to p<0.01). DISCUSSION AND CONCLUSIONS: IPT cognitive training, when delivered in the early stages of psychosis (within 18 months from FEP), seems to be particularly effective in improving cognitive flexibility and long-term memory. We did not see improvements in those who had a longer duration of illness who also underwent the same treatment. Cognitive flexibility is linked to clinical insight and social cognition. Therefore, improving this function may lead to a better outcome for patients. PMID- 26156819 TI - [Perinatal depression and affective bonds: experience in close relationship during pregnancy]. AB - AIM: This study aims to investigate the influence of the "romantic attachment" style, stressful life events, social factors on the risk of developing a depression during pregnancy and on the severity of depressive symptoms. METHODS: The study started with a screening on a sample of 453 women, during their third trimester of pregnancy, to which has been administered a survey data form, the Edinburgh Postnatal Depression Scale (EPDS) and the Experience in Close Relationship (ECR). Based on the results at EPDS, a clinical group of pre-natal depression (D=89) was selected and compared with a control group (C=89), in regards to psychopathological and social variables, exposure to stressful life events and attachment patterns. Analysis of correlation were performed to evaluate the influence of these factors on depressive symptoms severity. RESULTS: In D group, 52.8% of subjects reported previous psychiatric disorders and 49.4% a familiarity; 29.2% of these women complains of conflicts with their family of origin and 32.6% with partner. The ECR showed a prevalence of "fearful-avoidant" attachment style in clinical group (29.2% vs 1.1%, p=0.000); besides, ECR dimensions ("Avoidance", "Anxiety"), correlate with the severity of depressive symptoms. CONCLUSIONS: Positive family history for psychiatric disorders and an insecure romantic attachment might influence the development and the severity of perinatal depression. PMID- 26156820 TI - Psychotherapeutic treatment of eating disorders improve dissociative experiences and impulse regulation but not alexithymia. A case series report. AB - AIM: Eating disorders (EDs) are complex conditions associated with disability and a high rate of mortality. Typical characteristics of these diseases are dissociation, alexithymia and impulse dysregulation, all strategies dealing with negative emotions and regulate negative affect and anxiety. Our study aimed to assess the effectiveness of intensive psychological treatment for EDs, with particular reference to the above mentioned clinical characteristics. METHODS: Eight outpatients with eating disorders in psychotherapeutic treatment were evaluated in two stages after one year (T1 and T2), using the Eating Disorder Inventory II, the Toronto Alexithymia Scale 20, and the Dissociative Experiences Scale. RESULTS: Wilcoxon test showed significant reductions in DES score as well as in two subscales of the EDI-2, Impulse Regulation and Body Dissatisfaction (I EDI2 and BD-EDI2), while alexithymia levels did not show any difference. CONCLUSIONS: We can confirm the effectiveness of psychotherapy in people with EDs as regards dissociative moments, impulsivity and body dissatisfaction. However, alexithymia remains unchanged, possibly because of its deep emotional nature. PMID- 26156821 TI - Cannabis use and genital self-mutilation: an update of case reports. AB - We reported and compared two case reports of genital self-mutilation with concurrent increasing psychotic symptoms resulting from substance abuse such as cannabis and alcohol. PMID- 26156822 TI - [In Process Citation]. PMID- 26156823 TI - Association Between Childhood Residential Mobility and Non-medical Use of Prescription Drugs Among American Youth. AB - INTRODUCTION: Prescription drug abuse is a public health epidemic, resulting in 15,000 deaths annually. Disruption of childhood residence has been shown to increase drug-seeking behavior among adolescents; however, little research has explored its association specifically with non-medical use of prescription drugs (NMUPD). The objective of the study was to measure the association between residential mobility and NMUPD. METHODS: The 2010 National Survey on Drug Use and Health data were analyzed for 15,745 participants aged 12-17 years. NMUPD was defined as self-report of any non-medical use (i.e., taking a prescription drug that was not prescribed to them or consumption for recreational purposes) of tranquilizers, pain relievers, sedatives, or stimulants. Logistic regression for survey data was used to estimate the association between residential mobility and NMUPD, adjusting for potential confounders. RESULTS: After controlling for demographic, intrapersonal, interpersonal, and community factors, adolescents with low mobility (1-2 moves in the past 5 years) and residential instability (>=3 moves) were 16% (OR 1.16, 95% CI 1.01, 1.33) and 25% (OR 1.25, 95% CI 1.00, 1.56) more likely to report NMUPD compared to non-mobile adolescents (0 moves). Low-mobile adolescents were 18% (OR 1.18, 95% CI 1.01, 1.38) more likely to abuse pain relievers, specifically. No relationship was found between moving and tranquilizer, stimulant, or sedative use. DISCUSSION: Increasing childhood residential mobility is associated with NMUPD; therefore, efforts to prevent NMUPD should target mobile adolescents. Further examination of the psychological effects of moving and its association with pain reliever abuse is indicated. PMID- 26156824 TI - Adolescent and Adult Clients in Prenatal Case Management: Differences in Problems and Interventions Used. AB - OBJECTIVES: This study sought to characterize differences between pregnant adolescents and adults in the types of problems addressed by case managers, and to assess subsequent differences in the types of interventions used with both groups. METHODS: Data stem from 3947 client encounters, provided by 223 case managers in 92 Medicaid-reimbursed prenatal case management programs; the clients were confirmed to be either adolescents (<20 years of age) or adults. Case managers provided information on each client encounter that occurred during 10 workdays over a 20 workday period using the Case Management Intervention Record , a data collection tool. The Chi square test and the Mann-Whitney U test were used to compare the types and number of problems, the types of intervention received, and the mean number of intervention minutes between adolescents and adults. RESULTS: Adolescents experienced an average of 3.9 problems whereas adults experienced an average of 3.2 problems (p < 0.001). Compared to adults, adolescents were significantly more likely to experience problems in the areas of pregnancy health, family, education/job, transportation, and housing. With respect to breadth of interventions, adolescent clients were significantly more likely to receive support, clinical acts, and to be given tangible items compared to adult clients. On average, case managers spent significantly more time per encounter with adolescents than with adults overall (mean 56.6 vs. 50.3 min), and on educating, assessing, coaching, and monitoring. CONCLUSION: Age related differences have both programmatic and provider implications. The intervention typology can be used to evaluate PCM programs serving high risk population. PMID- 26156825 TI - First Trimester Levels of BV-Associated Bacteria and Risk of Miscarriage Among Women Early in Pregnancy. AB - OBJECTIVES: Prior studies have examined the role of bacterial vaginosis (BV) and increased risk of miscarriage; however the risk has been modest and many BV positive pregnant women deliver at term. BV is microbiologically heterogeneous, and thus the identification of specific BV-associated bacteria associated with miscarriage is warranted. METHODS: We measured the presence and level of seven BV associated bacteria prior to 14 weeks gestation among urban pregnant women seeking routine prenatal care at five urban obstetric practices at Temple University Hospital in Philadelphia PA from July 2008 through September 2011. 418 Pregnant women were included in this assessment and 74 experienced a miscarriage. RESULTS: Mean log concentration of BVAB3 was significantly higher among women experiencing a miscarriage (4.27 vs. 3.71, p value = 0.012). Younger women with high levels of BVAB3 had the greatest risk of miscarriage. In addition, we found a significant decreased risk of miscarriage among women with higher log concentrations of Leptotrichia/Sneathia species or Megasphaera phylotype 1-like species early in pregnancy. CONCLUSIONS FOR PRACTICE: The identification of selected vaginal bacteria associated with an increased risk of miscarriage could support screening programs early in pregnancy and promote early therapies to reduce early pregnancy loss. PMID- 26156826 TI - The Relationship Between Apparent Temperature and Daily Number of Live Births in Montreal. AB - OBJECTIVES: Temperature is a hypothesized determinant of early delivery, but seasonal and long term trends, delayed effects of temperature, and the influence of extreme cold temperatures have not yet been addressed. We aim to study the influence of apparent temperature on daily number of births, considering lag structures, seasonality and long term trends. METHODS: We used daily number of births in conjunction with apparent outdoor temperatures between 1981 and 2010 in Montreal. We used Poisson regression combined with a distributed lag nonlinear model to consider non-linear relationships between temperature and daily number of births across specific lag periods. RESULTS: We found that apparent temperature was associated with the daily number of births in Montreal, with a 1 day delay. We found an increase in births on hot days, and decrease on cold days, both offset by a harvesting effect after 4 and 5 days. CONCLUSIONS FOR PRACTICE: This study suggests that the number of births is affected by extreme temperatures. Obstetric and perinatal service providers should be prepared for spikes in the number of births caused by extreme temperatures. PMID- 26156827 TI - "Do You Wanna Breathe or Eat?": Parent Perspectives on Child Health Consequences of Food Insecurity, Trade-Offs, and Toxic Stress. AB - OBJECTIVES: This study among 51 parents of young children under age four investigated how parents that report marginal, low and very low food security characterize how trade-offs associated with food insecurity affect parents' mental health and child well-being. METHODS: We carried out 51 semi-structured audio-recorded interviews after participants responded to a survey regarding food security status and maternal depressive symptoms. Each interview was transcribed. Through a content analysis, we coded "meaning units" in each manuscript and organized them by themes in ATLAS.ti. Among participants reporting both food insecurity and depressive symptoms, we identified three primary areas of concern: trade-offs, mental health, and child well-being. RESULTS: Parents described how trade-offs associated with food insecurity have a profound relationship with their mental health and home environment that strongly affects young children. Descriptions of hardships include anxiety and depression related to overdue bills and shut-off notices, strains with housing costs, and safety. Parents described how their own frustration, anxiety, and depression related to economic hardship have a negative impact on their children's physical health, and their social and emotional development. CONCLUSIONS: Parents in food insecure households recognize that trade-offs between food and other basic necessities are associated with their personal stress and poor mental health that, in turn, affects their children's health and development. Partnerships between healthcare providers, policymakers, and parents are essential to successfully address and prevent the poor child health outcomes of toxic stress associated with food insecurity and poverty. PMID- 26156828 TI - Exploring Maternal Perceptions of Infant Sleep and Feeding Method Among Mothers in the United Kingdom: A Qualitative Focus Group Study. AB - BACKGROUND: In a context with strong rhetorical support for breastfeeding in the health system, yet extremely low rates of breastfeeding after hospital discharge, U.K. women's decisions about infant feeding reflect the reality of competing priorities in their lives, including obtaining adequate sleep. Popular wisdom in the U.K. tightly links breastfeeding and inadequate night-time sleep. Mothers are advised by peers and family to introduce formula or solid foods to infants to promote longer sleep. OBJECTIVES: The first objective of this study was to investigate women's understandings of the nature of infant sleep and their perceptions of links between infant feeding method and sleep. The second was to explore how these perceptions influence infant feeding and sleep practices. Underpinning our work is the understanding that infant care choices result from trade-offs by which mothers strive to balance infant- and self-care. METHODS: We conducted seven focus groups with mothers of infants in two regions of the U.K. Verbatim transcripts were thematically coded and emergent themes were identified. RESULTS: We found clearly diverging narratives between breastfeeding and formula feeding mothers. Breastfeeding mothers viewed the fragmentary nature of infant sleep as natural, while mothers who were formula feeding felt this was a problem to be fixed. CONCLUSIONS AND PRACTICE: The strategies used to promote infant and maternal sleep in each group were aligned with their underlying perception of how infant sleep works. Maternal perceptions of the nature of infant sleep and its relation to infant feeding method impact infant care practices in the first year of life. PMID- 26156829 TI - Maternal Chlamydia Infection During Pregnancy and Risk of Cyanotic Congenital Heart Defects in the Offspring. AB - OBJECTIVES: Genital Chlamydia is a common bacterial sexually-transmitted infection among reproductive aged women, particularly younger populations. Cyanotic congenital heart defects (CCHDs) constitute about one quarter of all cardiac malformations at birth, and are associated with high rate of morbidity and mortality. Epidemiological research on the association between maternal Chlamydia during pregnancy and CCHDs in the offspring is lacking. METHODS: Using data from the 2012 United States birth certificates, we examined the association between CCHDs and prenatal exposure to Chlamydia among live singleton births with CCHDs (n = 2487) and unaffected singleton births (n = 3,334,424). We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis for all CCHDs combined, and isolated CCHDs (without other major congenital malformations). RESULTS: Overall 1.7% of case and 1.7% of control women reported having Chlamydia during their pregnancies. After controlling for potential confounders, we found a weak positive association between maternal Chlamydia during pregnancy and all CCHDs combined (aOR = 1.39; 95% CI 1.02-1.90). The positive association persisted for isolated CCHD cases, but with marginal significance (aOR = 1.34; 95% CI 0.96 1.74). Subgroup analyses for younger women showed an increased risk for CCHDs; however, the associations were not statistically significant. CONCLUSIONS: Maternal exposure to Chlamydia during pregnancy was weakly associated with a higher risk of CCHDs in the offspring. The finding should be interpreted with caution due to limitations of birth certificate data. Future studies using more robust data sources are warranted to further study the association between maternal Chlamydia during pregnancy and CCHDs in the offspring. PMID- 26156830 TI - Ultrasonic assessment of the effects of self-assembling peptide scaffolds on preventing enamel demineralization. AB - OBJECTIVES: This study evaluates the effect of self-assembling peptide P11-4 (Curodont Repair, CDR) on bovine enamel remineralization by measuring changes in ultrasonic propagation velocity. METHODS: Six specimens per group were prepared by sectioning bovine teeth into enamel blocks. These blocks were then immersed in lactic acid buffer solution (pH = 4.75) for 10 min twice a day and stored in artificial saliva. Other specimens were first treated with CDR, followed by a 10 min immersion in the lactic acid buffer solution twice a day, before storage in artificial saliva. The propagation time of longitudinal ultrasonic waves was measured using a pulser/receiver. Six specimens were used for each treatment protocol. The obtained data were statistically analyzed using ANOVA followed by Tukey's honestly significant difference tests (alpha = 0.05). Specimens were observed using laser scanning microscopy and scanning electron microscopy. RESULTS: Sonic velocity was found to decrease with time for specimens stored in the demineralizing solution. On the other hand, increases in sonic velocity were found for specimens treated with CDR. These specimens also exhibited signs of mineral deposition. CONCLUSIONS: By measuring the ultrasonic propagation velocity, it can be concluded that CDR application has an ability to promote bovine enamel remineralization. PMID- 26156833 TI - A giant cyst of the wrist. PMID- 26156831 TI - High expression of carbonic anhydrase IX is significantly associated with glandular lesions in gastroesophageal junction and with tumorigenesis markers BMI1, MCM4 and MCM7. AB - BACKGROUND: Carbonic anhydrase IX (CA9) is a transmembrane glycoprotein related to hypoxia. Increased CA9 expression has been associated with decreased survival and cancer progression and has been targeted as a potential therapy for several cancers, including esophageal cancer. The reported percentages of expression of CA9 in esophageal adenocarcinoma vary, and CA9 expression in precancerous esophageal lesions has not been well studied. METHODS: In this study, we investigated CA9 expression in esophageal cancers and in precancerous lesions and explored the association of CA9 expression with prognostic factors and with stem cell and tumorigenesis-related markers including BMI1, cyclin E, ki67, MCM4 and MCM7 expression. Previously constructed tissue microarrays consisting of samples of 7 tissue types (columnar cell metaplasia, Barrett esophagus, low- and high grade dysplasia, esophageal adenocarcinoma, squamous epithelium, and squamous cell carcinoma) were used for the immunostaining of CA9, BMI1, cyclin E, Ki67, MCM4 and MCM7. RESULTS AND DISCUSSION: CA9 high expression occurred more frequently in glandular mucosa with or without dysplasia than in squamous epithelium or squamous cell carcinoma. Survival duration of esophageal adenocarcinoma did not significantly differ between patients with high CA9 expression and those with low expression. High CA9 expression is significantly associated with BMI1, cyclin E, Ki67, MCM4 and MCM7 expression. CONCLUSIONS: High CA9 expression may be related to the acidic environment caused by gastroesophageal reflux disease in the gastroesophageal junction and associated with tumorigenesis through BMI1, MCM4 and MCM7. PMID- 26156832 TI - May spa therapy be a valid opportunity to treat hand osteoarthritis? A review of clinical trials and mechanisms of action. AB - Osteoarthritis (OA) is the most common form of arthritis and its current treatment includes non-pharmacological and pharmacological modalities. Spa therapy represents a popular treatment for many rheumatic diseases. The aim of this review was to summarize the currently available information on clinical effects and mechanisms of action of spa therapy in OA of the hand. We conducted a search of the literature to extract articles describing randomized clinical trials (RCTs) in hand OA published in the period 1952-2015. We identified three assessable articles reporting RCTs on spa therapy in hand OA. Data from these clinical trials support a beneficial effect of spa therapy on pain, function and quality of life in hand OA. Spa therapy seems to have a role in the treatment of hand OA. However, additional RCTs are necessary to clarify the mechanisms of action and the effects of the application of thermal treatments. PMID- 26156834 TI - Vitamin D deficiency in a patient with HDR syndrome. AB - The case of a patient with clinical symptoms, laboratory and imaging findings of hypoparathyroidism, sensorineural deafness, renal dysplasia HDR, or Barakat syndrome (hypoparathyroidism, deafness, renal dysplasia), and vitamin D deficiency, is presented. A Caucasian man aged 51 years with a history of chronic hypocalcaemia since childhood, was admitted with hypertonia of the body and extremities, and loss of consciousness. On admission, he was found to have severe hypocalcaemia, hyperphosphataemia, severe hypoparathyroidism, low serum magnesium and mild renal insufficiency. Calcium gluconate was administered intravenously supplemented with magnesium, and the patient recovered consciousness while clinical and laboratory findings improved. Evaluation revealed left renal aplasia and sensorineural deafness affecting both ears. Vitamin D deficiency was also present. He was given calcium and vitamin D supplements orally, and the hypocalcaemia was corrected. This case is described as it is an extremely rare case of HDR syndrome with concurrent vitamin D deficiency. PMID- 26156835 TI - Aches, pains and headache: an unusual combination of hypothyroidism, vitamin D deficiency, cervical radiculopathy and cortical vein sinus thrombosis. AB - A young obese woman was admitted with vague aches and pains, including a headache. At first a provisional diagnosis of depression/myofacial pain syndrome was considered. Later, on evaluation, she was diagnosed to have hypothyroidism and vitamin D deficiency. One week into treatment, her neck pain and headache got worse. Examination of the fundus showed tortuous vessels, papilloedema and intraretinal haemorrhages. MR venogram of the brain was performed, which revealed the presence of thrombosis in the left transverse sinus, left sigmoid sinus and left internal jugular vein. This report is an unusual presentation of neuropsychiatric symptoms in a patient where overlapping diagnoses confound the clinical picture and test the clinical acumen of the physician. A careful history followed by a focused clinical examination and evaluation will help to delineate potential confounders. The report further highlights the importance of clinical medicine even in this era of 'investigative medicine'. PMID- 26156836 TI - Simultaneous occurrence of Meckel's diverticulum and patent urachus. AB - The simultaneous occurrence of a Meckel's diverticulum and a patent urachus is very uncommon. We describe the occurrence and surgical treatment of Meckel's diverticulum and an urachal anomaly in a 1-year-old boy. The patient had intermittent production of clear fluid from the patent urachus, which disappeared after surgical resection. PMID- 26156837 TI - Moxonidine for tramadol withdrawal symptoms during detoxification. AB - It is well documented in the literature that noradrenergic pathways are key in the manifestation of opioid withdrawal symptoms, which is why clonidine is used as an off-label agent in opioid detoxification regimens given its anti sympathetic properties. Moxonidine is a selective I1-imidazoline receptor agonist, similar to clonidine but with no alpha2-adrenergic agonist activity and subsequently fewer side effects. We report the case of a 33-year-old woman with a 15-year history of tramadol use who was admitted voluntarily for detoxification. She was started on moxonidine and had an uneventful detoxification. Two months after discharge, the patient maintained tramadol abstinence with good tolerability to moxonidine. To the best of our knowledge, this has not been previously reported in the medical literature. PMID- 26156838 TI - Cutaneous collagenous vasculopathy: a rare cause of generalised cutaneous telangiectasia. AB - Cutaneous collagenous vasculopathy is a rare cutaneous microangiopathy of unknown aetiology with only 27 cases reported to date. It is characterised clinically by generalised cutaneous telangiectasias and microscopically by dilation and marked thickening of the walls of superficial dermal blood vessels. Differential diagnosis should be performed with other causes of disseminated telangiectasias, including generalised essential telangiectasia, from which it is clinically indistinguishable. We report a new case of cutaneous collagenous vasculopathy in a 61-year-old woman presenting with a 5-year history of asymptomatic telangiectasias distributed symmetrically on her upper and lower limbs and highlight the importance of clinicopathological correlation for the diagnosis of this disease. PMID- 26156839 TI - Undetected supraventricular tachycardia causing congestive heart failure: a pitfall of remote monitoring system. AB - Remote monitoring systems with automated clinician alerts are a milestone development for implantable cardiovascular devices, and improve the quality of life for patients and physicians by reducing the number of conventional clinic visits. In addition, remote monitoring systems can detect many bradyarrhythmias and tachyarrhythmias earlier than traditional methods, although these devices are not perfect. We report the case of an 80-year-old woman with an implanted pacemaker and a remote monitoring system that failed to report acute heart failure at 10 months after implantation. ECG and telemetry revealed relatively slow supraventricular tachycardia, which did not trigger the alert, and catheter ablation successfully controlled the heart failure. Subsequent analysis revealed that the monitoring function had detected the arrhythmia as frequent premature ventricular contraction, although the arrhythmia did not trigger the automated clinician alert. Therefore, remote monitoring systems with accurate settings are essential, although conventional monitoring methods are still important for some patients. PMID- 26156840 TI - Urrets-Zavalia syndrome after laser-assisted in situ keratomileusis (LASIK). AB - We report a case of fixed, non-reactive pupil (Urrets-Zavalia syndrome) in a 34 year-old patient following laser-assisted in situ keratomileusis (LASIK) caused probably by intermittent postoperative intraocular pressure fluctuations. This case highlights the possibility of a fixed and dilated pupil even after LASIK, a technically non-intraocular surgery, which is due to a preventable cause: postoperative intraocular pressure fluctuations. To the best of our knowledge, this is the first report of Urrets-Zavalia syndrome following LASIK. PMID- 26156841 TI - Multiple whitish colonic sessile polyps in a patient with changes in bowel habit. PMID- 26156842 TI - Refractory ventricular fibrillation managed by coronary revascularisation performed during ongoing manual cardiac resuscitation lasting 11/2 h. AB - Myocardial infarction is the most common cause of ventricular arrhythmias. Although there have been several improvements and refinements in coronary catheterisation with percutaneous intervention over the years, this intervention is still rarely considered during active ongoing resuscitation of patients, especially in cases of persistent ventricular arrhythmias. We present a case of refractory ventricular fibrillations due to in-stent thrombosis that was managed by emergent coronary angiogram and stent placement during ongoing cardiopulmonary resuscitation in a code that lasted about 11/2 h. The patient subsequently made an excellent recovery and was discharged home 13 days later. PMID- 26156843 TI - Multicystic dedifferentiated retroperitoneal liposarcoma: tumour cyst fluid analysis and implications for management. AB - Liposarcomas are soft tissue sarcomas of adipocyte origin. We describe a case of a dedifferentiated retroperitoneal liposarcoma with an unusual presentation on recurrence as a large, multicystic tumour. The patient was a 72-year-old woman who had undergone multiple treatments including two prior resections. For her most recent locoregional disease recurrence, the patient was offered surgical debulking for symptom palliation. At this operation, performed after two cycles of chemotherapy, the tumour cyst fluid was analysed and found to have a predominance of immune cells with no identifiable malignant cells. This case and the results of our tumour cyst fluid analysis raise several interesting considerations for the management of this unique situation in a rare disease. PMID- 26156844 TI - Left ventricular pseudoaneurysm following undiagnosed myocardial infarction: the curious case of the woman with three ventricles. PMID- 26156845 TI - Pediatric Surgical Care in a Dutch Military Hospital in Afghanistan. AB - BACKGROUND: From August 2006-August 2010, as part of the ISAF mission, the Armed Forces of the Netherlands deployed a role 2 enhanced Medical Treatment Facility (R2E-MTF) to Uruzgan province, Afghanistan. Although from the principle doctrine not considered a primary task, care was delivered to civilians, including many children. Humanitarian aid accounted for a substantial part of the workload, necessitating medical, infrastructural, and logistical adaptations. Particularly pediatric care demanded specific expertise and equipment. In our pre-deployment preparations this aspect had been undervalued. Because these experiences could be influential in future mission planning, we analyzed our data and compared them with international reports. METHODS: This is a retrospective, descriptive study. Using the hospital's electronic database, all pediatric cases, defined as patients <17 years of age, who were admitted between August 2006 and August 2010 to the Dutch R2E-MTF at Multinational Base Tarin Kowt (MBTK), Urzugan, Afghanistan were analyzed. RESULTS: Of the 2736 admissions, 415 (15.2 %) were pediatric. The majority (80.9 %, 336/415) of these admissions were for surgical, often trauma-related, pathology and required 610 surgical procedures, being 26 % of all procedures. Mean length of stay was 3.1 days. The male to female ratio was 70:30. Girls were significantly younger of age than boys. In-hospital mortality was 5.3 %. CONCLUSION: Pediatric patients made up a considerable part of the workload at the Dutch R2E-MTF in Uruzgan, Afghanistan. This is in line with other reports from the recent conflicts in Iraq and Afghanistan, but used definitions in reported series are inconsistent, making comparisons difficult. Our findings stress the need for a comprehensive, prospective, and coalition-wide patient registry with uniformly applied criteria. Civilian disaster and military operational planners should incorporate reported patient statistics in manning documents, future courses, training manuals, logistic planning, and doctrines, because pediatric care is a reality that cannot be ignored. PMID- 26156846 TI - Short-Term Performance Improvement of a Continuing Medical Education Program in a Low-Income Country. AB - BACKGROUND: The Haitian Annual Assembly for Orthopaedic Trauma (HAAOT) is a CME conference designed to help Haitian orthopaedic surgeons improve their knowledge and skills. The effectiveness of international CME conferences has not been studied. We hypothesized that HAAOT improves participants' short-term performance on knowledge-based assessments. METHODS: Data were prospectively collected from 57 Haitian and 21 foreign orthopaedic surgeons and residents who attended HAAOT using pre- and post-presentation questions. An audience response system was used to capture responses to 40 questions. Five additional demographic questions were used to train participants and to record unique audience member responses. Questions were projected in English and in French. Two-sided paired t tests were used to compare pre- and post-test scores. ANOVA with post-hoc unpaired t tests was used to compare among demographic groups. RESULTS: Response rate Median response rate was 77.4 % per day (Range: 76.5-85.9 % per day). Pre-test scores Pre-test scores averaged 21 % for Haitians and 39 % for foreigners (p < 0.0001), and were similar among Haitian attendings and residents. Pre-post differences Scores improved by 8 % for Haitians (p < 0.0001) and 10 % for foreigners (p < 0.01) after didactic presentations. Among sub-groups, Haitian attendings improved on average by 18 % compared to 6 % for residents (p < 0.0001). Haitian attending improvement trended toward significance when compared to foreign attendings (p < 0.08). CONCLUSIONS: Our study is the first to show improved short-term knowledge performance using an audience response system during a CME conference in a low income country. CME conferences in low-income countries can be an effective tool to increase surgeon knowledge, and audience response systems can help engage participants and track outcomes. PMID- 26156847 TI - The SF-36 and 6-Minute Walk Test as Predictors of Complications After Major Surgery, Clinical Impact. PMID- 26156848 TI - Fluorometric CCHFV OTU protease assay with potent inhibitors. AB - Crimean-Congo hemorrhagic fever virus (CCHFV) is a deadly virus that has been listed in the Category C as a potential bioterror agent. There are no specific therapies against CCHFV, which urges identification of potential therapeutic targets and development of CCHFV therapies. CCHFV OTU protease takes an important role in viral invasion through antagonizing NF-kappaB signaling. Inhibition of CCHFV OTU protease by small molecules warrants an exciting potential as antiviral therapeutics. Here we report the expression and purification of a C-His-tagged recombinant CCHFV OTU protease in E. coli BL21 (DE3) host strain. Activity of the refolded purified recombinant viral OTU protease has been validated with a UB-AMC fluorescent assay. In addition, we show a dose-dependent inhibition of the viral OTU protease by two small molecules. This study provides a reliable approach for recombinant expression and purification of CCHFV OTU protease, and demonstrates validation of OTU protease activity and its inhibition based on a UB-AMC florescent assay. PMID- 26156849 TI - Repeated evolution and the impact of evolutionary history on adaptation. AB - BACKGROUND: Whether natural selection can erase the imprint of past evolutionary history from phenotypes has been a topic of much debate. A key source of evidence that present-day selection can override historically contingent effects comes from the repeated evolution of similar adaptations in different taxa. Yet classic examples of repeated evolution are often among closely related taxa, suggesting the likelihood that similar adaptations evolve is contingent on the length of time separating taxa. To resolve this, we performed a meta-analysis of published reports of repeated evolution. RESULTS: Overall, repeated evolution was far more likely to be documented among closely related than distantly related taxa. However, not all forms of adaptation seemed to exhibit the same pattern. The evolution of similar behavior and physiology seemed frequent in distantly related and closely related taxa, while the repeated evolution of morphology was heavily skewed towards closely related taxa. Functionally redundant characteristics alternative phenotypes that achieve the same functional outcome-also appeared less contingent. CONCLUSIONS: If the literature provides a reasonable reflection of the incidence of repeated evolution in nature, our findings suggest that natural selection can overcome contingent effects to an extent, but it depends heavily on the aspect of the phenotype targeted by selection. PMID- 26156850 TI - Development of a mixed feed strategy for a recombinant Pichia pastoris strain producing with a de-repression promoter. AB - BACKGROUND: Recombinant protein production in the yeast Pichia pastoris is usually based on the alcohol oxidase promoters pAOX1 and pAOX2, which are regulated by methanol and strongly repressed by other C-sources, like glycerol and glucose. However, the use of methanol brings several disadvantages, which is why current trends in bioprocess development with P. pastoris are focussing on minimizing the required amount of methanol or even avoid its employment. In this respect novel promoter systems which do not rely on methanol have been investigated and promoter variants were designed to fine-tune gene expression. Amongst these novel promoter systems, mutated AOX promoters, which are regulated by available carbon source concentration (so-called de-repressed promoters), are currently raising attention. However, the main disadvantage of such a production system is that expression and growth usually cannot happen concomitantly resulting in low space-time-yields. RESULTS: Here we show the development of a mixed-feed strategy for an industrial recombinant P. pastoris de-repression strain aiming at increased productivity and maximum space-time-yield. By doing dynamic experiments we determined a ratio between the specific substrate uptake rates of glycerol and sorbitol allowing a more than 2-fold increased productivity compared to the conventional single substrate de-repression strategy. CONCLUSION: Based on our results we recommend adjusting q(s glycerol) = 0.04 g g(-1) h(-1) and q(s sorbitol) = 0.055 g g(-1) h(-1) to obtain highest productivity with a P. pastoris de-repression strain. Our methodological approach of designing mixed feed strategies based on physiological strain characterization using dynamic experiments proved to be beneficial. PMID- 26156851 TI - Serum Stem Cell Factor Assay in Elderly Poor Responder Patients Undergoing IVF: A New Biomarker to Customize Follicle Aspiration Cycle by Cycle. AB - In humans, stem cell factor (SCF), produced during follicular phase, may reflect a successful stimulation and oocyte maturation and so it may be a predictor of in vitro fertilization (IVF) outcome. An observational cohort study was conducted on 37 poor responders scheduled for fresh nondonor IVF/intracytoplasmic sperm injection treatment with standard controlled ovarian stimulation (COS) using recombinant follicle-stimulating hormone (rFSH; S-COS group). A total of 35 women received a second treatment using both rFSH and recombinant luteinizing hormone (rLH; LH-COS group). From 144 samples collected at pickup day, serum concentration of SCF (s-SCF) and follicular levels of SCF (f-SCF) were measured by enzyme-linked immunosorbent assay (ELISA) kit. No differences were observed between the 2 protocols in terms of both f-SCF and s-SCF levels. The comparison between f-SCF and s-SCF levels showed a strong linear correlation. The comparison between s-SCF levels and clinical outcomes showed a statistically significant correlation between both the number of metaphase II (MII) oocytes retrieved and the embryos obtained after fertilization. Cases with at least 3 MII oocytes showed s-SCF values >800 pg/mL, 2 MII oocytes >600 pg/mL, and 1 MII oocytes >400 pg/mL. In 100% of cases with s-SCF <400 pg/mL, no MII oocytes were recovered. All 5 pregnancies occurred in patients with s-SCF values >1000 pg/mL. The introduction of s-SCF assay in the management of poor-responder patients may contribute to solving the dilemma of whether to cancel or proceed with the stimulation cycle. PMID- 26156852 TI - Effect of Exogenous Anti-Mullerian Hormone Treatment on Cryopreserved and Transplanted Mouse Ovaries. AB - Follicle loss occurs after ovary cryopreservation and transplantation. To preserve the follicle pool of cryopreserved or grafted ovaries, anti-Mullerian hormone (AMH), which inhibits ovarian follicle recruitment, was used in a mouse model. In experiment 1, ovaries were vitrified warmed with different doses of AMH (0, 5, 15, or 45 MUg/mL) supplementation. In experiment 2, AMH (0, 50, 250, and 1250 MUg/mL) was injected into mice before and/or after cryopreserved ovary autotransplantation, and the recipients remained for 7 or 28 days after grafting. Ovaries were evaluated by follicle morphology, density, and apoptosis ratio. Additionally, serum follicle-stimulating hormone was measured in experiment 2. Significantly decreased follicle apoptosis were detected in AMH-treated groups when compared to the control ovaries in experiment 1, meanwhile no positive effect of exogenous AMH was found in experiment 2. Thus, we suggest AMH supplementation during ovary vitrification warming has beneficial effect on reducing follicle apoptosis. PMID- 26156853 TI - Fas and Fas-Ligand in Eutopic and Ectopic Endometrium of Women With Endometriosis: The Possible Immune Privilege of Ectopic Endometrium. AB - The Fas/Fas-Ligand system is an important mediator of apoptosis. We analyzed their expression in tissue specimens obtained from 33 women with severe endometriosis and 18 women without endometriosis. Immunostaining for Fas-Ligand in the eutopic endometrium was stronger in the epithelial cells of secretory phase, while the epithelial cells of endometriotic lesions showed a significantly stronger staining for Fas-Ligand independently from the menstrual phase (P < 0.01). Immunostaining for Fas in the eutopic endometrium showed a reduced staining during the proliferative phase, whereas it was strong in the secretory phase. The epithelial cells of the ectopic endometrium showed a reduced staining for Fas independently from the menstrual phase with respect to the eutopic tissue (P < 0.01). The reduced expression of Fas in the ectopic endometrium with the contemporary higher expression of Fas-Ligand in the corresponding cells suggests a possible immune privilege of this tissue. PMID- 26156855 TI - Mode of Delivery in Stillbirth, 1995-2004. AB - OBJECTIVE: There are no national reports on the mode of delivery in pregnancies that end in stillbirth. We aimed at analyzing the cesarean delivery rates in pregnancies resulting in stillbirth over a 10-year period in the United States. MATERIALS AND METHODS: This was a retrospective analysis evaluating data from the 1995 to 2004 US linked live birth-infant death files reported by the National Center for Health Statistics to examine the cesarean delivery rates in singleton pregnancies with and without stillbirth. RESULTS: There were 39 797 616 singleton births registered in the database after the 20th week of gestation. During the study period, there were 243 979 stillbirths (0.61 per 100). Significant differences in stillbirths were noted in the African American population, nonmarried patients, in mothers who smoked, and at the extremes of the patients reproductive age (P < .01). The overall cesarean delivery rate in liveborn was 23.54% (9 309 961 cases) and 10.5% in stillbirth (25 558 cases; P < .01). The rate of cesarean delivery increased in liveborn (from 20.8% in 1995 to 28.9% in 2004; 28% overall increase) and in stillbirth (9.5% in 1995 to 11.23% in 2004; 15% overall increase). The rates of primary and repeat cesarean operations increased with gestational age in the stillbirth group. This pattern was not observed in the liveborn group. CONCLUSION: This analysis indicates that the cesarean delivery rates increased both in liveborn and in stillbirth from 1995 to 2004. This epidemiological observation deserves new clinical investigations to understand the clinical reasons, driving this obstetrical practice and the financial and societal impact that it portends. PMID- 26156854 TI - Damage-Associated Molecular Pattern and Fetal Membrane Vascular Injury and Collagen Disorganization in Lipopolysaccharide-Induced Intra-amniotic Inflammation in Fetal Sheep. AB - To understand the changes in the structural integrity of fetal membranes during intrauterine inflammation, we evaluated the time course of expression and localization of damage-associated molecular patterns (DAMPs) and injury/remodeling in collagen and vascular smooth muscle. Time-mated ewes received intra-amniotic (IA) saline or IA lipopolysaccharide (LPS) for 5 hours to 15 days prior to a preterm delivery at 125 +/- 2 days (n = 5-7 animals/group). The DAMP high mobility group box 1 (HMGB1) protein assessed by Western blot was induced within 24 hours after IA LPS in the fetal membranes, and HMGB1 expression was localized to amnion epithelium, chorion vascular endothelium, and infiltrating inflammatory cells by immunohistology. Markers of vascular injury, intercellular adhesion molecule 1, and tissue plasminogen activator messenger RNA (mRNA) expression increased 5 to 12 hours after IA LPS in the chorioamnion indicating vascular injury. Chorion vascular remodeling with increased chorion arteriolar smooth muscle actin expression by morphometric analyses of immunohistology was noted 15 days after IA LPS. Collagen expression was nonhomogeneous by histochemical staining, and there was a trend toward decreased mRNA expression of collagen subunit COL5A1 after IA LPS. CONCLUSIONS: Intrauterine inflammation induced early increases in HMGB1 in the chorioamnion with a concomitant vascular injury followed by chorion arteriolar hypertrophy. There was nonhomogeneous collagen expression in the chorioamnion. These results have implications for understanding the pathogenesis of IA inflammation-induced preterm rupture of membranes. PMID- 26156856 TI - Relative importance of AMH and androgens changes with aging among non-obese women with polycystic ovary syndrome. AB - BACKGROUND: To assess the changes in phenotypes and endocrine profiles of women with polycystic ovary syndrome (PCOS) with advancing age. METHODS: In a cross sectional study conducted at a private tertiary fertility clinical and research center we identified anonymized electronic records of 37 women who had presented with a prior diagnosis of PCOS. They were stratified as younger (<35 years) and older (>=40 years). As controls, we identified 43 women with age-specific low functional ovarian reserve and 14 young women with normal functional ovarian reserve. Endocrine profiles for each group were evaluated based on total (TT) and free testosterone (FT), anti-Mullerian hormone (AMH) and sex hormone binding globulin (SHBG). RESULTS: Patients including those with PCOS were mostly non obese, evidenced by normal BMIs (21.6 +/- 6.0) with no differences between study groups. Young PCOS patients presented with a typical pattern of significant hyperandrogenemia and elevated AMH in comparison to young women with normal functional ovarian reserve [TT 44.0 (32.9-58.7) vs. 23.9 (20.3-28.1) ng/dL, (P<0.05); and AMH 7.7 (6.2-9.1) vs. 2.5 (2.0-3.0) ng/mL, (P<0.05)]. With advancing age, hyperandrogenemia in PCOS diminished in comparison to young women with normal functional ovarian reserve, resulting in similar TT levels [28.6 (19.7-37.5) vs. 23.9 (20.3-28.1) ng/dL]. Though also declining, AMH remained significantly elevated in older PCOS women in comparison to young women with normal functional ovarian reserve [4.0 (2.7-5.2) vs. 2.5 (2.0-3.0) ng/mL, (P<0.05)]. Patients with low functional ovarian reserve demonstrated significantly lower AMH at both young and older ages compared to women with normal functional ovarian reserve (P<0.05 for both). However, among patients with low functional ovarian reserve no differences were observed at young compared to older ages in TT [17.6 (12.9-24.1) vs. 18.1 (13.6-24.1) ng/dL)] and AMH [0.4 (0.3 0.6) vs. 0.3 (0.2-0.5) ng/mL]. SHBG did not differ significantly between groups but trended opposite to testosterone. CONCLUSIONS: The PCOS population predominantly consisted of non-obese phenotype at both young and advanced ages. This suggests that patients with "classical" obese PCOS phenotype rarely reach tertiary infertility care, while non-obese PCOS patients may be more resistant to lower levels of infertility treatments. PCOS patients also demonstrate more precipitous declines in testosterone then AMH with advancing age. These data support incorporation of AMH as diagnostic criterion for PCOS regardless of age, and imply that testosterone should not be relied upon in the diagnosis of PCOS in older women. PMID- 26156858 TI - Temperature-controlled MPa-pressure ultrasonic cell manipulation in a microfluidic chip. AB - We study the temperature-independent impact on cell viability of relevant physical parameters during long-term, high-acoustic-pressure ultrasonic exposure in a microfluidic chip designed for ultrasonic-standing-wave trapping and aggregation of cells. We use a light-intensity method and 5 MUm polymer beads for accurate acoustic pressure calibration before injecting cells into the device, and we monitor the viability of A549 lung cancer cells trapped during one hour in an ultrasonic standing wave with 1 MPa pressure amplitude. The microfluidic chip is actuated by a novel temperature-controlled ultrasonic transducer capable of keeping the temperature stable around 37 degrees C with an accuracy better than +/-0.2 degrees C, independently on the ultrasonic power and heat produced by the system, thereby decoupling any temperature effect from other relevant effects on cells caused by the high-pressure acoustic field. We demonstrate that frequency modulated ultrasonic actuation can produce acoustic pressures of equally high magnitudes as with single-frequency actuation, and we show that A549 lung cancer cells can be exposed to 1 MPa standing-wave acoustic pressure amplitudes for one hour without compromising cell viability. At this pressure level, we also measure the acoustic streaming induced around the trapped cell aggregate, and conclude that cell viability is not affected by streaming velocities of the order of 100 MUm s(-1). Our results are important when implementing acoustophoresis methods in various clinical and biomedical applications. PMID- 26156857 TI - Subcutaneous fat necrosis in neonates with hypoxic ischaemic encephalopathy registered in the Swiss National Asphyxia and Cooling Register. AB - BACKGROUND: Neonates with hypoxic ischaemic encephalopathy (HIE) are routinely treated with therapeutic hypothermia (TH) for 72 h in order to improve neurological outcome. Subcutaneous fat necrosis (SCFN) is an adverse event occurring in neonates with HIE. METHODS: We analyzed risk factors for SCFN regarding demographic factors, cooling methods and deviation from target temperature range during hypothermia therapy. Data of all neonates registered in the National Asphyxia and Cooling Register in Switzerland between 2011 and 2013 were analyzed. RESULTS: 2.8% of all cooled neonates with HIE developed SCFN. Perinatal and neonatal characteristics did not differ between neonates with and without SCFN. Applied cooling methods did not correlate with the occurrence of SCFN. In neonates with SCFN 83.3% of all noted temperatures were within the target temperature range versus 77.5% in neonates without SCFN. Neonates with SCFN showed 3.6% of all measured temperatures below target temperature range compared to 12.7% in neonates without SCFN. CONCLUSION: Subcutaneous fat necrosis in the neonate with HIE undergoing TH is a potential adverse event that seems to occur independently from the whole-body cooling method applied and proportion of temperature measurements outside target temperature range. In this cohort, moderate overcooling associated with moderate hypothermia (33.0-34.0 degrees C) does not seem to be an independent risk factor for SCFN. There is no correlation between the severity of HIE and incidence of SCFN. PMID- 26156859 TI - Understanding the genetic architectonics of complex CNS traits: Lost by the association, but found in the interaction? AB - Recent evidence supports the value of endophenotypes and genome-wide association studies in psychiatric genetics, and their importance for dissecting the neural pathways and molecular mechanisms of complex neuropsychiatric disorders. Continuing this important discussion, here we outline three new mechanisms by which novel classes of genes may facilitate CNS pathogenesis without directly worsening its individual 'established' endophenotypes. These putative genetic mechanisms can apply to other human disorders in general, and may also be used for designing novel effective CNS drug treatments. PMID- 26156860 TI - Rating scales to measure side effects of antipsychotic medication: A systematic review. AB - INTRODUCTION: Many patients experience side effects during treatment with antipsychotics. This article reviews the clinical use and psychometric characteristics of rating scales used to assess side effects in patients treated with antipsychotics. METHODS: A systematic literature search was performed using the electronic databases PubMed and Embase, with predefined search terms. RESULTS: In total, 52 different scales were used in the 440 articles retrieved. For multiple side effects measured with one scale, the Udvalg for Kliniske Undersogelser Side Effects Rating Scale for Clinicians was used the most, whereas the Liverpool University Neuroleptic Side Effect Rating Scale had the best psychometric characteristics (Cronbach's alpha 0.81 and test-retest reliability 0.89). The Simpson Angus Scale was used the most to rate extrapyramidal side effects, although the Maryland Psychiatric Research Center scale had the best characteristics (Cronbach's alpha 0.80, test-retest reliability 0.92 and inter rater reliability 0.81-0.90). The Arizona Sexual Experience Scale was used the most to assess sexual dysfunction, but the Antipsychotics and Sexual Functioning Questionnaire and the Nagoya Sexual Functioning Questionnaire had the best characteristics. CONCLUSION: This review will help researchers and clinicians make a purpose-oriented choice of which scale to use. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42014013010. PMID- 26156861 TI - Biofunctional properties of Eruca sativa Miller (rocket salad) hydroalcoholic extract. AB - Eruca sativa Miller is a worldwide common alimentary plant (rocket leaves). The aim of this study was to correlate the potential in vitro scavenging activity of the E. sativa hydroalcoholic extract (HAE) with its in vivo hypoglycaemic effect. In DDPH free radical (DFR) and ferric-reducing antioxidant power assays, HAE in a concentration dependent manner (25-100 MUg/mL) displayed a strong scavenging activity with maximum effect of 88% and 75% at 100 MUg/mL, respectively. Daily administration of HAE (50 mg/kg; p.o.) in the in vivo model of alloxan-induced diabetic rabbits for 28 days showed significant reduction in glycaemia, also supported by recovery of body weight. In conclusion, our results give preliminary information on the potential use of this plant as a nutraceutical, useful to control and/or prevent a hyperglycaemic status. PMID- 26156862 TI - Human sporotrichosis beyond the epidemic front reveals classical transmission types in Espirito Santo, Brazil. AB - Sporotrichosis has emerged as the main subcutaneous mycosis of humans and animals around the world. With particular differences in frequency, the major species includes Sporothrix brasiliensis, S. schenckii, S. globosa and S. luriei. In Brazil, the main aspect of this epidemic is based on the zoonotic transmission through the scratches and bites of diseased cats contaminated with S. brasiliensis. Areas free of feline sporotrichosis are poorly characterised in Brazil. We investigated by molecular tools the epidemiology of human sporotrichosis in the Espirito Santo (ES) state, an area adjacent to Rio de Janeiro where is the epicentre of the long-lasting outbreak of cat-transmitted sporotrichosis. The human cases in the ES state reveal the prevalence of classical transmission types where subjects are mainly infected by accidental traumatic inoculation during manipulation of contaminated plant material. In agreement with an environmental source, Sporothrix schenckii was the major aetiological agent in the classical transmission. Unlike Rio de Janeiro, this study shows that cat-transmitted epidemic in Espirito Santo is still scanty, although the geographic proximity and similar climatic features. Sporothrix brasiliensis was the agent in the feline-transmitted cases. Sporothrix globosa was isolated from a patient with fixed cutaneous lesions that did not report any contact with diseased animals. In conclusion, beyond the borders of Rio de Janeiro epidemic, agents of sporotrichosis in Espirito Santo show a scattered occurrence with high species diversity. PMID- 26156863 TI - Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell. AB - The polyamines (PAs) spermidine, spermine, putrescine and cadaverine are an essential class of metabolites found throughout all kingdoms of life. In this comprehensive review, we discuss their metabolism, their various intracellular functions and their unusual and conserved regulatory features. These include the regulation of translation via upstream open reading frames, the over-reading of stop codons via ribosomal frameshifting, the existence of an antizyme and an antizyme inhibitor, ubiquitin-independent proteasomal degradation, a complex bi directional membrane transport system and a unique posttranslational modification hypusination-that is believed to occur on a single protein only (eIF-5A). Many of these features are broadly conserved indicating that PA metabolism is both concentration critical and evolutionary ancient. When PA metabolism is disrupted, a plethora of cellular processes are affected, including transcription, translation, gene expression regulation, autophagy and stress resistance. As a result, the role of PAs has been associated with cell growth, aging, memory performance, neurodegenerative diseases, metabolic disorders and cancer. Despite comprehensive studies addressing PAs, a unifying concept to interpret their molecular role is missing. The precise biochemical function of polyamines is thus one of the remaining mysteries of molecular cell biology. PMID- 26156864 TI - Inactivation of group II intron RmInt1 in the Sinorhizobium meliloti genome. AB - Group II introns are self-splicing catalytic RNAs that probably originated in bacteria and act as mobile retroelements. The dispersal and dynamics of group II intron spread within a bacterial genome are thought to follow a selection-driven extinction model. Likewise, various studies on the evolution of group II introns have suggested that they are evolving toward an inactive form by fragmentation, with the loss of the intron 3'-terminus, but with some intron fragments remaining and continuing to evolve in the genome. RmInt1 is a mobile group II intron that is widespread in natural populations of Sinorhizobium meliloti, but some strains of this species have no RmInt1 introns. We studied the splicing ability and mobility of the three full-length RmInt1 copies harbored by S. meliloti 1021, and obtained evidence suggesting that specific mutations may lead to the impairment of intron splicing and retrohoming. Our data suggest that the RmInt1 copies in this strain are undergoing a process of inactivation. PMID- 26156865 TI - Three-dimensional fluid-attenuated inversion recovery sequence for visualisation of subthalamic nucleus for deep brain stimulation in Parkinson's disease. AB - INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson's disease (PD). However, targeting the STN is difficult due to its relatively small size and variable location. The purpose of this study was to assess which of the following sequences obtained with the 3.0 T MR system can accurately delineate the STN: coronal 3D fluid attenuated inversion recovery (FLAIR), 2D T2*-weighted fast-field echo (T2*-FFE) and 2D T2-weighted turbo spin-echo (TSE) sequences. METHODS: We included 20 consecutive patients with PD who underwent 3.0 T MR for DBS targeting. 3D FLAIR, 2D T2*-FFE and T2-TSE images were obtained for all study patients. Image quality and demarcation of the STN were analysed using 4-point scales, and contrast ratio (CR) of the STN and normal white matter was calculated. The Friedman test was used to compare the three sequences. RESULTS: In qualitative analysis, the 2D T2* FFE image showed more artefacts than 3D FLAIR or 2D T2-TSE, but the difference did not reach statistical significance. 3D FLAIR images showed significantly superior demarcation of the STN compared with 2D T2*-FFE and T2-TSE images (P < 0.001, respectively). The CR of 3D FLAIR was significantly higher than that of 2D T2*-FFE or T2-TSE images in multiple comparison correction (P < 0.001), but there was no significant difference in the CR between 2D T2*-FFE and T2-TSE images. CONCLUSION: Coronal 3D FLAIR images showed the most accurate demarcation of the STN for DBS targeting among coronal 3D FLAIR, 2D T2*-FFE and T2-TSE images. PMID- 26156866 TI - Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis. AB - INTRODUCTION: The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. METHODS: Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. RESULTS: Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-alpha, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. CONCLUSIONS: Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A. PMID- 26156867 TI - Dissociation predicts treatment response in eye-movement desensitization and reprocessing for posttraumatic stress disorder. AB - Using clinical data from a specialized trauma clinic, this study investigated pretreatment clinical factors predicting response to eye-movement desensitization and reprocessing (EMDR) among adult patients diagnosed with posttraumatic stress disorder (PTSD). Participants were evaluated using the Clinician-Administered PTSD Scale (CAPS), the Symptom Checklist-90-Revised, the Beck Depression Inventory, and the Dissociative Experiences Scale before treatment and were reassessed using the CAPS after treatment and at 6-month follow-up. A total of 69 patients underwent an average of 4 sessions of EMDR, and 60 (87%) completed the posttreatment evaluation, including 8 participants who terminated treatment prematurely. Intent-to-treat analysis revealed that 39 (65%) of the 60 patients were classified as responders and 21 (35%) as nonresponders when response was defined as more than a 30% decrease in total CAPS score. The nonresponders had higher levels of dissociation (depersonalization and derealization) and numbing symptoms, but other PTSD symptoms, such as avoidance, hyperarousal, and intrusion, were not significantly different. The number of psychiatric comorbidities was also associated with treatment nonresponse. The final logistic regression model yielded 2 significant variables: dissociation (p < .001) and more than 2 comorbidities compared to none (p < .05). These results indicate that complex symptom patterns in PTSD may predict treatment response and support the inclusion of the dissociative subtype of PTSD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. PMID- 26156868 TI - Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics. AB - Biological and biomedical research relies on comprehensive understanding of protein-coding transcripts. However, the total number of human proteins is still unknown due to the prevalence of alternative splicing. In this paper, we detected 31,566 novel transcripts with coding potential by filtering our ab initio predictions with 50 RNA-seq datasets from diverse tissues/cell lines. PCR followed by MiSeq sequencing showed that at least 84.1% of these predicted novel splice sites could be validated. In contrast to known transcripts, the expression of these novel transcripts were highly tissue-specific. Based on these novel transcripts, at least 36 novel proteins were detected from shotgun proteomics data of 41 breast samples. We also showed L1 retrotransposons have a more significant impact on the origin of new transcripts/genes than previously thought. Furthermore, we found that alternative splicing is extraordinarily widespread for genes involved in specific biological functions like protein binding, nucleoside binding, neuron projection, membrane organization and cell adhesion. In the end, the total number of human transcripts with protein-coding potential was estimated to be at least 204,950. PMID- 26156869 TI - EndoS and EndoS2 hydrolyze Fc-glycans on therapeutic antibodies with different glycoform selectivity and can be used for rapid quantification of high-mannose glycans. AB - Enzymes that affect glycoproteins of the human immune system, and thereby modulate defense responses, are abundant among bacterial pathogens. Two endoglycosidases from the human pathogen Streptococcus pyogenes, EndoS and EndoS2, have recently been shown to hydrolyze N-linked glycans of human immunoglobulin G. However, detailed characterization and comparison of the hydrolyzing activities have not been performed. In the present study, we set out to characterize the enzymes by comparing the activities of EndoS and EndoS2 on a selection of therapeutic monoclonal antibodies (mAbs), cetuximab, adalimumab, panitumumab and denosumab. By analyzing the glycans hydrolyzed by EndoS and EndoS2 from the antibodies using matrix-assisted laser desorption ionization time of flight, we found that both the enzymes cleaved complex glycans and that EndoS2 hydrolyzed hybrid and oligomannose structures to a greater extent compared with EndoS. A comparison of ultra-high-performance liquid chromatography (LC) profiles of the glycan pool of cetuximab hydrolyzed with EndoS and EndoS2 showed that EndoS2 hydrolyzed hybrid and oligomannose glycans, whereas these peaks were missing in the EndoS chromatogram. We utilized this difference in glycoform selectivity, in combination with the IdeS protease, and developed a LC separation method to quantify high mannose content in the Fc fragments of the selected mAbs. We conclude that EndoS and EndoS2 hydrolyze different glycoforms from the Fc glycosylation site on therapeutic mAbs and that this can be used for rapid quantification of high mannose content. PMID- 26156871 TI - TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine. AB - BACKGROUND: In traditional medicine, there has been a great deal of research on the effects exhibited by medicinal materials. To study the effects, resources that can systematically describe the chemical compounds in medicinal materials are necessary. In recent years, numerous databases on medicinal materials and constituent compounds have been constructed. However, because these databases provide differing information and the sources of such information are unclear or difficult to verify, it is difficult to decide which database to use. Moreover, there is much overlapping information. The aim of this study was to construct a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine (TM-MC), for which medicinal materials are listed in the Korean, Chinese, and Japanese pharmacopoeias and information on the compound names of medicinal materials can easily be confirmed online. DESCRIPTION: To provide information on the chemical compounds of medicinal materials, chromatography articles from MEDLINE and PubMed Central were searched. After chemical compounds of medicinal materials were extracted by manually investigating the full-text of articles, a database of information on about 14,000 compounds from 536 medicinal materials was built. The database also provides links to the articles from which each medicinal material and chemical compound were extracted. CONCLUSION: TM-MC database provides information on medicinal materials and their chemical compounds from chromatography articles in MEDLINE and PubMed Central. Researchers can easily check relevant information through the links to articles. PMID- 26156870 TI - DOME/GALT type adenocarcimoma of the colon: a case report, literature review and a unified phenotypic categorization. AB - Several types of colorectal cancers are associated with a prominent lymphoid component, which is considered a positive prognostic factor. We report a case of a dome-type carcinoma of the cecum in a 57 year old female. The sessile, non polypoid lesion histologically consisted of a tubulovillous adenoma with low grade dysplasia. The submucosal invasive component showed low-grade architectural features that included cystically dilated glands containing eosinohilic debris. Immunohistochemical studies displayed retention of the four mistmach repair proteins, consistent with a stable phenotype. After 3 years, the patient remains free of recurrence. A literature review highlighted striking similarities between dome-type carcinoma and the gut-associated lymphoid tissue carcinoma, the two sharing an intimate association with the gut associated lymphoid tissue.The two variants might therefore be grouped into a unified category. PMID- 26156872 TI - Hypertension, Diabetes Type II, and Their Association: Role of Arterial Stiffness. AB - In patients with both hypertension and type II diabetes, the systolic blood pressure (SBP) increases linearly with age, while that of diastolic blood pressure (DBP) declines curvilinearly as early as age 45, all suggesting the development of increased arterial stiffness. Increased stiffness is an important, independent, and significant risk predictor in subjects with hypertension and diabetes. In patients with both diseases, stiffness assessed at the same mean arterial pressure (MAP) was significantly higher in diabetic patients. Arterial stiffness is related to age, heart rate (HR), and MAP, but in diabetic patients, it also related to diabetes duration and insulin treatment (IT). In the metabolic syndrome (MetSyn), diabetes also acts on the small arteries through capillary rarefaction to reduce the effective length of the arterial tree, increases the reflected pulse wave and thus the pulse pressure (PP). These studies indicate that diabetes and hypertension additively contribute to increased pulsatility and suggest that any means to reduce stiffness would be beneficial in these conditions. PMID- 26156873 TI - Blood Pressure Lowering Medication, Visit-to-Visit Blood Pressure Variability, and Cognitive Function in Old Age. AB - BACKGROUND: Visit-to-visit blood pressure (BP) variability is associated with cognitive impairment. We assessed to what extent the association between BP variability and cognitive impairment is mediated by the association of BP lowering medication (BPLM) with both BP variability and cognition. METHODS: We studied 5,606 participants from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). BP was measured every 3 months during 3.2 years; BP variability was defined as the SD of BP measurements during follow-up. Cognitive function was assessed at baseline and during follow-up using the Stroop test, Letter-Digit Coding test, and immediate and delayed Picture-Word Learning tests. Multivariate regression models were used with and without adjustments for BPLM to calculate the percentage to which BPLM mediated the association between BP variability and cognition. RESULTS: Participants taking calcium antagonists had a higher score in baseline Letter-Digit Coding test (mean difference (95% confidence interval (CI) 0.45 (0.06; 0.88). Participants taking beta-blockers had a steeper decline in Stroop test (additional change per year (95% CI) 0.40 (0.09; 0.70) and Letter-Digit Coding test (0.08 (-0.15; -0.02)). Furthermore, a steeper decline in Stroop test was found in participants taking renin-angiotensin system (RAS) inhibitors (0.50 (0.16; 0.85). Systolic BP variability was higher in participants taking beta-blockers and RAS inhibitors (mean difference in systolic BP variability in mm Hg (95% CI) 0.75 (0.45; 1.04) and 1.37 (1.04; 1.71) respectively). Participants taking diuretics, calcium antagonists, and RAS inhibitors had a higher diastolic BP variability (mean difference in diastolic BP variability in mm Hg (95% CI) 0.27 (0.04; 0.49), 0.37 (0.12; 0.62) and 0.65 (0.37; 0.93) SD, respectively). Beta estimates remained essentially the same when we adjusted for BPLM in the association of BP variability with cognitive function. CONCLUSIONS: The association between BP variability and cognitive impairment was not mediated by BPLM. PMID- 26156874 TI - Rethinking our approach to postpartum haemorrhage and uterotonics. PMID- 26156875 TI - GEANT4 calculations of neutron dose in radiation protection using a homogeneous phantom and a Chinese hybrid male phantom. AB - The purpose of this study is to verify the feasibility of applying GEANT4 (version 10.01) in neutron dose calculations in radiation protection by comparing the calculation results with MCNP5. The depth dose distributions are investigated in a homogeneous phantom, and the fluence-to-dose conversion coefficients are calculated for different organs in the Chinese hybrid male phantom for neutrons with energy ranging from 1 * 10(-9) to 10 MeV. By comparing the simulation results between GEANT4 and MCNP5, it is shown that using the high-precision (HP) neutron physics list, GEANT4 produces the closest simulation results to MCNP5. However, differences could be observed when the neutron energy is lower than 1 * 10(-6) MeV. Activating the thermal scattering with an S matrix correction in GEANT4 with HP and MCNP5 in thermal energy range can reduce the difference between these two codes. PMID- 26156876 TI - Hypometabolism of watershed areas of the brain in HTLV-1-associated myelopathy/tropical spastic paraparesis. AB - In previous studies of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), areas of slow blood flow in the spinal cord were related to pathological changes. While the pathological changes in the brain are milder than those in the spinal cord, they are also more significant in sites with slow blood flow. In this study, we investigated brain glucose metabolism in slow blood flow areas using fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Clinical features and brain (18)F FDG-PET parameters were analyzed in six patients with HAM/TSP. For comparison of PET data, eight healthy volunteers were enrolled as normal controls (NLs). Glucose metabolism in the watershed areas of the middle and posterior cerebral arteries, as compared with that in the occipital lobes as a control, was significantly lower in HAM/TSP patients than in NLs. This result confirmed the relationship between slow blood flow areas and hypometabolism in HAM/TSP, and is consistent with previous findings that pathological changes are accentuated in sites with slow blood flow. PMID- 26156877 TI - Hirschsprung's disease in children with Mowat-Wilson syndrome. AB - BACKGROUND: Hirschsprung's disease (HSCR) is cited as a classical component in the constellation of features found in children with Mowat-Wilson syndrome (MWS), which is caused by a mutation of the ZEB2 gene. The prevalence and phenotype of HSCR in those with MWS has yet to be determined. Similarly, it is not known if children with MWS who undergo a curative pull-through operation experience similar functional outcomes. We aimed to delineate the clinical features of those with MWS and HSCR and to determine if these patients experience unfavourable outcomes following pull-through surgery. METHODS: A systematic review of the literature using the key search term "Mowat Wilson" was performed using three online databases. Clinical data were collected on all patients with a diagnosis of MWS confirmed by ZEB2 analysis. Data regarding bowel function in children with biopsy-proven HSCR were recorded where available. Statistical analysis was performed using SPSS (v. 20.0). RESULTS: Fifty-two articles were reviewed in the final analysis, incorporating data on 256 patients with a diagnosis of MWS. HSCR was diagnosed in 111 patients (43.4%). Males with HSCR had a slightly increased risk of genital tract anomalies (e.g. hypospadias) compared to those without HSCR (RR 1.79, p = 0.05). Data pertaining to disease phenotype and functional outcome were only available on 42 and 13 patients, respectively. Rectosigmoid aganglionosis was the most common sub-type of HSCR, being described 26 patients (66.7%), albeit accounting for a lower proportion than would normally be expected in an HSCR population. Only two patients (15.4%) were described as having normal bowel function at follow-up with the remainder having terminal stomas, or experiencing troublesome persistent bowel symptoms and recurrent enterocolitis. CONCLUSION: Hirschsprung's disease is present in approximately 45% of patients diagnosed with MWS. Although there is a relative lack of data available on the clinical phenotype of HSCR in this group and their functional outcome following pull-through operation, our data suggest an increased prevalence of long-segment aganglionosis and an increased risk of clinically significant persistent bowel symptoms following pull-through surgery, in many cases necessitating terminal stoma formation. PMID- 26156878 TI - Rectal suction biopsy for the diagnosis of Hirschsprung's disease: a systematic review of diagnostic accuracy and complications. AB - PURPOSE: Rectal suction biopsy (RSB) combined with acetylcholinesterase (AChE) staining is currently the gold standard for the diagnosis of Hirschsprung's disease (HD). However, some pathologists are still reluctant to diagnose HD in RSBs as it requires thick submucosal tissue to confirm the absence of ganglion cells. Furthermore, insufficient specimens and adverse events have been reported. The objective of this study was to determine the diagnostic accuracy and incidence of complications of RSBs in patients suspected of HD based on a systematic review of the published literature. METHODS: A literature-based search for relevant publications was conducted using multiple online databases. Staining for AChE/hematoxylin and eosin should have been used to evaluate RSBs. The number of true-positive, false-positive, true-negative and false-negative results was recorded and data on RSB-related complications was extracted. Pooled incidence rates and odds ratios (ORs) with 95% confidence intervals (CI) were calculated using standardized statistical methodology. RESULTS: Fifty-eight studies met defined inclusion criteria, reporting a total of 14,053 RSBs. The median cohort size consisted of 72 patients (range 1-766) with a median age of 14.4 months (range 1 day-66 years) at time of biopsy. In 89.93% (CI 89.11-90.70%), RSB provided adequate tissue for the diagnosis of HD. Insufficient specimens were obtained in 10.07% (CI 9.30-10.89%) and in 8.46 % (CI 7.55-9.46%) RSB was repeated. The incidence of HD was 19.13% (CI 18.25-20.03%). Mean sensitivity of RSB was 96.84% (CI 95.57-97.47%) and mean specificity was 99.42% (CI 99.17 99.57%). The overall complication rate was 0.65% (CI 0.46-0.91%) with persistent rectal bleeding requiring blood transfusion in 0.53% (CI 0.36-0.77%), bowel perforation in 0.06% (CI 0.02-0.18%) and pelvic sepsis in 0.06% (CI 0.02-0.18%). Complications were significantly more frequent in newborns and infants compared to older children (OR 9.00 [CI 4.75-17.07], p < 0.0001). CONCLUSIONS: RSB combined with AChE staining is a simple, safe and accurate method for the diagnosis of HD. The risk for RSB-related complications is higher in newborns and infants. PMID- 26156879 TI - Syndromic Hirschsprung's disease and associated congenital heart disease: a systematic review. AB - PURPOSE: Hirschsprung's disease (HD) occurs as an isolated phenotype in 70% of infants and is associated with additional congenital anomalies or syndromes in approximately 30% of patients. The cardiac development depends on neural crest cell proliferation and is closely related to the formation of the enteric nervous system. HD associated with congenital heart disease (CHD) has been reported in 5 8% of cases, with septation defects being the most frequently recorded abnormalities. However, the prevalence of HD associated with CHD in infants with syndromic disorders is not well documented. This systematic review was designed to determine the prevalence of CHD in syndromic HD. METHODS: A systematic review of the literature using the keywords "Hirschsprung's disease", "aganglionosis", "congenital megacolon", "congenital heart disease" and "congenital heart defect" was performed. Resulting publications were reviewed for epidemiology and morbidity. Reference lists were screened for additional relevant studies. RESULTS: A total of fifty-two publications from 1963 to 2014 reported data on infants with HD associated with CHD. The overall reported prevalence of HD associated with CHD in infants without chromosomal disorders was 3%. In infants with syndromic disorders, the overall prevalence of HD associated with CHD ranged from 20 to 80 % (overall prevalence 51%). Septation defects were recorded in 57% (atrial septal defects in 29%, ventricular septal defects in 32%), a patent ductus arteriosus in 39%, vascular abnormalities in 16%, valvular heart defects in 4% and Tetralogy of Fallot in 7%. CONCLUSION: The prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities. PMID- 26156880 TI - Plasma Free Amino Acid Profiles Predict Four-Year Risk of Developing Diabetes, Metabolic Syndrome, Dyslipidemia, and Hypertension in Japanese Population. AB - Plasma free amino acid (PFAA) profile is highlighted in its association with visceral obesity and hyperinsulinemia, and future diabetes. Indeed PFAA profiling potentially can evaluate individuals' future risks of developing lifestyle related diseases, in addition to diabetes. However, few studies have been performed especially in Asian populations, about the optimal combination of PFAAs for evaluating health risks. We quantified PFAA levels in 3,701 Japanese subjects, and determined visceral fat area (VFA) and two-hour post-challenge insulin (Ins120 min) values in 865 and 1,160 subjects, respectively. Then, models between PFAA levels and the VFA or Ins120 min values were constructed by multiple linear regression analysis with variable selection. Finally, a cohort study of 2,984 subjects to examine capabilities of the obtained models for predicting four year risk of developing new-onset lifestyle-related diseases was conducted. The correlation coefficients of the obtained PFAA models against VFA or Ins120 min were higher than single PFAA level. Our models work well for future risk prediction. Even after adjusting for commonly accepted multiple risk factors, these models can predict future development of diabetes, metabolic syndrome, and dyslipidemia. PFAA profiles confer independent and differing contributions to increasing the lifestyle-related disease risks in addition to the currently known factors in a general Japanese population. PMID- 26156882 TI - The Internal Structure of Macroporous Membranes and Transport of Surface-Modified Nanoparticles. AB - Understanding the morphological structure of membranes is essential to improve performance of membrane-based applications. In this paper, macroporous membranes were investigated and two methods introduced as an alternative for characterization of stereo-structure of the membranes. We combined the use of synchrotron X-ray nanotomography and small-angle X-ray scattering to examine the internal structure of cellulose acetate membranes with studies of the capture of surface-modified gold nanoparticles within these membranes. Finally, the morphological structures of macroporous membranes were visualized and their relationships with penetration tendency of surface-modified gold nanoparticles were explained. PMID- 26156881 TI - Distal and Proximal Influences on Men's Intentions to Resist Condoms: Alcohol, Sexual Aggression History, Impulsivity, and Social-Cognitive Factors. AB - Recent scientific evidence demonstrates that many young men commonly resist condom use with their female sex partners and that both alcohol intoxication and a history of sexual aggression may increase the risk of condom use resistance (CUR). Using a community sample of heterosexual male non-problem drinkers with elevated sexual risk (N = 311), this alcohol administration study examined the direct and indirect effects of intoxication and sexual aggression history on men's CUR intentions through a sexual risk analogue. State impulsivity, CUR related attitudes, and CUR-related self-efficacy were assessed as mediators. Results demonstrated that alcohol intoxication directly increased CUR intentions, and sexual aggression history both directly and indirectly increased CUR intentions. These findings highlight the importance of addressing both alcohol use and sexual aggression in risky sex prevention programs, as well as indicate the continued worth of research regarding the intersection of men's alcohol use, sexual aggression, and sexual risk behaviors, especially CUR. PMID- 26156883 TI - Effect of P2Y12 inhibitors on inflammation and immunity. AB - Platelet P2Y12 inhibitors form a major part of the treatment strategy for patients with acute coronary syndromes (ACS) due to the importance of the platelet P2Y12 receptor in mediating the pathophysiology of arterial thrombosis. It has been increasingly recognised that platelets also have a critical role in inflammation and immune responses. P2Y12 inhibitors reduce platelet release of pro-inflammatory alpha-granule contents and the formation of pro-inflammatory platelet-leukocyte aggregates. These are important mediators of inflammation in a variety of different contexts. Clinical evidence shows that P2Y12 inhibition by clopidogrel is associated with a reduction in platelet-related mediators of inflammation, such as soluble P-selectin and CD40L, following atherothrombosis. Clopidogrel in addition to aspirin, compared to aspirin alone, also reduces markers of systemic inflammation such as tumour necrosis factor (TNF) alpha and C reactive protein (CRP) following ACS. The more potent thienopyridine P2Y12 inhibitor, prasugrel, has been shown to decrease platelet P-selectin expression and platelet-leukocyte aggregate formation compared to clopidogrel. The PLATO study suggested that the novel P2Y12 inhibitor ticagrelor might improve clinical outcomes from pulmonary infections and sepsis compared to clopidogrel in patients with ACS. Ticagrelor is a more potent P2Y12 inhibitor than clopidogrel and also inhibits cellular adenosine uptake via equilibrative nucleoside transporter (ENT) 1, whereas clopidogrel does not. Further examination of the involvement of these mechanisms in inflammation and immunity is therefore warranted. PMID- 26156884 TI - Iron triad (Fe, Co, Ni) nanomaterials: structural design, functionalization and their applications. AB - The structure and the composition are two key factors that influence the physical, chemical, and other properties of materials. Correspondingly, structural design and functionalization with inorganic or organic materials provide efficient routes to enhancing some properties. Herein, iron triad nanomaterials, with a wide range of applications in energy, environment and other fields, were chosen as the target materials. This paper reviews various approaches for designing three typical structures (hollow and porous, ultrathin two-dimensional, and complex three-dimensional structures) of iron triad nanomaterials with high specific surface areas as well as their feasible functionalization for special purposes. Furthermore, some amazing work in recent years is introduced and discussed, especially in the energy field including energy transfer, conversion and storage, and in the environment field, including the adsorption and removal of harmful inorganic ions and organic pollutants. This review aims at developing potential applications of the nanomaterials using structural adjustment and functionalization to overcome their intrinsic shortcomings and enhance their performance. PMID- 26156885 TI - Angiogenesis, Proliferative Activity and DNA Ploidy in Oral Verrucous Carcinoma: A Comparative Study Including Verrucous Hyperplasia and Squamous Cell Carcinoma. AB - Verrucous carcinoma (VC) is a rare and distinct clinicopathologic variant of well differentiated squamous cell carcinoma (SCC). This study aims to evaluate the histomorphology, proliferative activity, level of angiogenesis, and DNA ploidy of these pathological entities. This was a retrospective-prospective study of 18 cases of verrucous hyperplasia (VH), 41 cases of VC, and 44 cases of SCC. Immunohistochemical analysis for Ki-67 (MIB-1) and CD34 were performed. The tumor proliferative index, endothelial proliferative index and microvascular density were calculated. DNA ploidy was determined using image cytometry. The age range and gender ratio were similar in all three groups. The differences in MIB-1 labeling index (p = 0.0001), microvascular density (p = 0.01), and endothelial proliferative index (p = 0.001) between VC and SCC were found to be statistically significant. A non-significant increasing trend was observed in all of these parameters between VH and VC. On ploidy analysis, 100 % of SCC cases were aneuploid, compared to 39 % of VH and 86 % of VC cases. Our study demonstrates a significant difference in tumor proliferation, microvessel density, and ploidy between VC and SCC while increasing trend between VH and VC. These parameters, along with morphological findings, may be useful in differentiating these entities in small mucosal biopsies. PMID- 26156886 TI - Association and Prognostic Significance of the Functional -1562C/T Polymorphism in the Promoter Region of MMP-9 in Turkish Patients with Gastric Cancer. AB - Matrix metalloproteinases (MMPs) are a group of zinc-dependent peptidases that participate in matrix turnover in solid malignancies. The aim of this study was twofold. First, we sought to investigate under a case-control design the association between the functional -1562C/T polymorphism in the promoter region of MMP-9 and gastric cancer (GC) in a Turkish sample. Second, we examined its prognostic significance in GC patients. A total of 144 subjects were enrolled in the case-control study (79 GC cases and 65 controls). Overall survival (OS) and progression-free survival (PFS) served as the main outcome measures in the longitudinal study. The MMP-9 -1562C/T polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The odds ratio (OR) of GC for the CC genotype relative to the CT+TT genotypes was not significant (OR = 0.89, 95 % confidence interval [CI] = 0.44-1.82, P = 0.75). These results did not change after allowance for age and sex in multivariable regression analysis (OR = 0.81, 95 % CI = 0.40-1.94, P = 0.84). When the MMP-9 1562C/T polymorphism was analyzed among GC patients in relation to OS and PFS, we found no significant differences between subjects with the CC and CT+TT genotypes. In conclusion, the results of our study did not point toward a major role of the MMP-9 -1562C/T polymorphism in the pathogenesis and clinical course of GC in Turkish subjects. PMID- 26156887 TI - Formulation and Pharmacokinetic Evaluation of Polymeric Dispersions Containing Valsartan. AB - BACKGROUND: Valsartan exhibits poor aqueous solubility and dissolution rate limited absorption. The lower solubility in the upper part of gastrointestinal tract (pH-dependant solubility) where its absorption window exists further contributes to the low oral bioavailability of valsartan. OBJECTIVE: The present work was aimed to improve the in vivo pharmacokinetics of valsartan by preparing amorphous polymeric dispersions using Eudragit E 100 as carrier. Eudragit E 100 is a cationic polymer soluble in gastric fluid up to pH 5.0 and exhibits pH dependent release. Hence, the dispersions prepared using Eudragit E 100 rapidly dissolves at lower pH presenting drug in molecularly dispersed and soluble form at its absorption site. METHODS: Polymeric solid dispersions were prepared in different drug-to-carrier ratios. The prepared dispersions were evaluated for drug-carrier interactions, solid-state transitions and drug-release properties with the help of Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and in vitro dissolution studies. The optimized formulation containing valsartan was tested in rats for bioavailability and pharmacokinetic parameters and compared with that of valsartan pure drug. RESULTS: The results from FTIR studies indicated no interactions between drug and excipients. DSC studies confirmed reduction in crystallinity of drug. The dissolution studies performed in 0.1 N HCl showed significant improvement (p < 0.05) in the dissolution of valsartan. In vivo pharmacokinetic studies showed 199 % relative bioavailability with significant improvement (p < 0.05) in area under the curve compared to valsartan pure drug. CONCLUSION: Eudragit E 100 can be used to improve the dissolution of drugs that show low solubility at lower pH and thereby enhancing the bioavailability. PMID- 26156888 TI - Gamma glutamyl transferase in 1744 patients with obstructive sleep apnea. PMID- 26156889 TI - Serum gamma glutamyl transferase in patients with sleep apnea-hypopnea. PMID- 26156891 TI - A Comparison of the Effects of Ethics Training on International and US Students. AB - As scientific and engineering efforts become increasingly global in nature, the need to understand differences in perceptions of research ethics issues across countries and cultures is imperative. However, investigations into the connection between nationality and ethical decision-making in the sciences have largely generated mixed results. In Study 1 of this paper, a measure of biases and compensatory strategies that could influence ethical decisions was administered. Results from this study indicated that graduate students from the United States and international graduate students studying in the US are prone to different biases. Based on these findings, recommendations are made for developing ethics education interventions to target these decision-making biases. In Study 2, we employed an ethics training intervention based on ethical sensemaking and used a well-established measure of ethical decision-making that more fully captures the content of ethical judgment. Similar to Study 1, the results obtained in this study suggest differences do exist between graduate students from the US and international graduate students in ethical decision-making prior to taking the research ethics training. However, similar effects were observed for both groups following the completion of the ethics training intervention. PMID- 26156890 TI - Comorbid depression in obstructive sleep apnea: an under-recognized association. AB - BACKGROUND: Obstructive sleep apnea (OSA) and depression may coexist in the same patient. This article aims to review the link between OSA and comorbid depression and critically evaluate the results of studies that assessed the correlation between OSA and depression, the impact of OSA treatment on comorbid depression, and the impact of comorbid depression on continuous positive airway pressure (CPAP) adherence. METHODS: An integrative review was conducted on English language studies and reports that assessed the relationship between OSA and depression. Studies were identified by searching PubMed, Web of Science and Google Scholar databases, and reference lists of included studies. RESULTS: Generally, cross-sectional studies show a higher prevalence of depression among OSA patients with both community and sleep disorder clinic samples. Nevertheless, the relationship between OSA and depression is complicated by the fact that the disorders have overlapping symptoms. Longitudinal studies demonstrate an increased risk of developing depression among people with OSA, as well as an association between OSA severity and the likelihood of developing depression. On the other hand, studies assessing the impact of CPAP therapy on depression among OSA patients report conflicting results. Therefore, it is essential to consider how the disorders affect one another and to understand the clinical consequences of treating each disorder in isolation. CONCLUSION: Depression is prevalent among patients with OSA both in the community and in sleep disorder clinics. Clinicians in general should be aware of this significant association and should aim to treat both disorders. PMID- 26156892 TI - A cohort study on the evolution of psychosocial problems in older patients with breast or colorectal cancer: comparison with younger cancer patients and older primary care patients without cancer. AB - BACKGROUND: Although older cancer survivors commonly report psychosocial problems, the impact of both cancer and ageing on the occurrence of these problems remains largely unknown. The evolution of depression, cognitive functioning, and fatigue was evaluated in a group of older cancer patients in comparison with a group of younger cancer patients and older persons without cancer. METHODS: Older (>=70 years) and younger cancer patients (50-69 years) with breast or colorectal cancer stage I-III, and older persons without cancer (>=70 years) were included. Data were collected at baseline and one year follow up and were available for 536 persons. Depression was evaluated with the 15-item Geriatric Depression Scale. Cognitive functioning was measured with the cognitive functioning subscale of the European Organization for Research and Treatment of Cancer. Fatigue was measured with a Visual Analogue Scale. Risk factors for depression, cognitive functioning, and fatigue were analysed using multivariate logistic regression analyses. Risk factors included cancer- and ageing-related factors such as functional status, cancer treatment, and comorbidities. RESULTS: The evolution of psychosocial problems was similar for the group of older (N = 125) and younger cancer patients (N = 196): an increase in depression (p < 0.01), slight worsening in cognitive functioning (p = 0.01), and no clear change in fatigue. Also, compared to the group of people without cancer (N = 215), the differences were small and after one year of follow-up only depression was more frequent in older cancer patients compared to older persons without cancer (18% versus 9%, p = 0.04). In multivariate analyses the main risk factors for psychosocial problems after one year follow-up were changes in functional status and presence of baseline depression, fatigue, or cognitive impairment. CONCLUSION: Over the course of one year after a diagnosis of cancer, cancer patients face increasing levels of depression and increasing difficulties in cognitive functioning. The main risk factor for psychosocial problems was presence of the problem at baseline. This calls for regular screening for psychosocial problems and exchange of information on psychosocial functioning between different health care providers and settings during the treatment and follow-up trajectory of cancer patients. PMID- 26156893 TI - Severe neurological consequences of subclavian steal in the setting of cardiogenic shock. PMID- 26156894 TI - Work disability assessment of cancer survivors: insurance physicians' perspectives. AB - BACKGROUND: Assessing work disability in cancer survivors is a complex decision making process. In the Netherlands, physicians employed by the Dutch Social Security Agency (SSA) play a key role in assessing work disability of cancer survivors on long-term sick leave. AIMS: To investigate the aspects physicians consider in assessing work disability in cancer survivors, their experiences related to the use of guidelines and their needs related to the use of a prediction rule that aims to support work disability assessments. METHODS: A qualitative study involving three consecutive focus group interviews, using a predetermined topic list. The interviews were recorded, transcribed and independently analysed using standard procedures of thematic analysis. RESULTS: The 29 participating physicians reported feeling responsible primarily for making correct assessments of cancer survivors' work disability, in which they predominantly investigate medical factors. Secondarily, non-medical factors related to the person, their work and/or their social environment were considered. Adherence to guidelines aiming to support physicians making such assessments was variable. CONCLUSIONS: In assessing work disability among cancer survivors on long-term sick leave, physicians considered medical and non-medical factors. The relevance of non-medical factors became more prominent in cases where medical issues were less obvious. There seems to be a need to enhance adherence to guidelines in order to support the work disability assessment of cancer survivors. The development of an implementation strategy for a prediction rule to support the work disability assessment of cancer survivors should be considered. PMID- 26156895 TI - The Role of Family on Hookah Smoking Initiation in Women: A Qualitative Study. AB - Hookah smoking has recently emerged as a popular alternative to cigarette smoking particularly among young adults and women. This study focused on the role of family members' smoking behaviours as a possible risk factor for initiation of hookah smoking in women. 36 in-depth interviews were conducted with Iranian women of diverse ages for understanding the factors contributing to the initiation of hookah smoking. Four main themes were identified from the data. This study focused on the role of family as a facilitator for hookah smoking initiation. The results of this study indicate that the entry of hookah into homes can be effective in the spread of hookah smoking among adult and young women, in three ways: Girls' participation in the preparation of hookah and the frequent observation of people who smoke hookah at home can be effective in hookah smoking initiation among young girls; the husband of a young woman has an important role in the initiation of smoking hookah; when parents invite children to smoke hookah at home, in order to protect them against public censure, the mother (a middle aged woman) may intend to start smoking hookah. Therefore, tobacco use prevention interventions should be focused on targeting the family as well. PMID- 26156896 TI - Does Nutrition Knowledge and Practice of Athletes Translate to Enhanced Athletic Performance? Cross-Sectional Study Amongst Nigerian Undergraduate Athletes. AB - INTRODUCTION & OBJECTIVES: Nutrition knowledge of an athlete, as well as practice, is expected to influence athlete's performance. The study assessed the nutrition knowledge and practice as well as athletes' performance and identified the factors predicting the athletes' performance. METHODOLOGY: A cross-sectional survey, involved 110 purposively selected undergraduate athletes (47 females, 63 males) of University of Ibadan, Nigeria, between July 2013 and December 2013. A semi-structured, self-administered questionnaire assessed the nutrition knowledge and practice. 24-hr diet recall and food frequency questionnaire were done. Anthropometric measurements were taken; body composition was determined by bioelectrical impedance analysis method. Handgrip strength (HGS), as an indirect measure of athlete performance, was assessed with the hand dynamometer. Chi square and t-test analysis were used for the bivariate analysis. Pearson correlation and simple linear regression were used to determine relationships and predict athletic performance. The level of statistical significance was p<0.05. RESULTS: More than half (58.2%) had good nutrition knowledge (NK), and 62.7% had good nutrition practices (NP). Majority (75.4%) had normal handgrip strength (HGS). More than 70.0% frequently do not consume cereals, roots and tubers, fruits and vegetables, legumes /nuts. About 30.0-40.0% frequently do not consume eggs/milk, meat/fish. Having good NK was significantly associated with good NP (chi2=15.520, p=0.000), but not with athlete's performance (HGS). There is no significant correlation between NK, NP, and HGS. There is a significant positive correlation between HGS and lean muscle mass (LMM) (r=.670, p=0.000), weight (r=.492, p=0.000), height (r=.521, p=0.000) and energy intake (r=.386, p=0.000). There is a significant negative correlation between HGS and percentage body fat (r=-.400, p=0.000). Athletes' performance was significantly predicted by the resting metabolic rate (beta=.454 C.I=0.011 to 0.045, p=0.003), Lean muscle mass (beta=.297 C.I=.059 to 0.562, p=0.024) and the weight (beta=.228, C.I=1.852 to .489, p=0.047). CONCLUSION: Having good nutrition knowledge or practice did not directly determine athletic performance. However, there is the need for nutrition education interventions, to improve athlete's performance by promoting adequate energy intake, lean muscle mass and appropriate weight gain in athletes. PMID- 26156897 TI - The Lived Experience of Domestic Violence in Iranian HIV-Infected Women. AB - Domestic violence is one of the most prevalent problems linked to HIV. Domestic violence in HIV-infected women has not been sufficiently explored, particularly in developing countries including Iran. This study aimed to explore the lived experience of domestic violence in Iranian HIV-infected women. A qualitative approach was used to conduct the study. Data were collected through semi structured, in-depth interviews with ten HIV-infected women and were analyzed using content analysis. During the data analysis, four main themes emerged including, "regretful past", "disappointing future", "loneliness", and "no other option", which refer to the condition that the participants experienced in their lives due to challenges that mainly stem from the experience of HIV-related domestic violence. HIV infection can be a risk factor for domestic violence. Health care providers need to address domestic violence during the assessment of HIV-infected women and make appropriate referrals for abused women. PMID- 26156898 TI - Lifestyle and Outcomes of Assisted Reproductive Techniques: A Narrative Review. AB - BACKGROUND: Studies reveal that lifestyles such as physical activity patterns, obesity, nutrition, and smoking, are factors that affect laboratory test results and pregnancy outcomes induced by assisted fertility techniques in infertile couples. The present study is a narrative review of studies in this area. METHODS: In this study, researchers conducted their computer search in public databases Google Scholar general search engine, and then more specific: Science Direct, ProQuest, SID, Magiran, Irandoc, Pubmed, Scopus, cochrane library, and Psych info; Cumulative Index to Nursing and Allied Health Literature (CINAHL), using Medical Subject Headings (MeSH) keywords: infertility (sterility, infertility), lifestyle (life behavior, lifestyle), Assisted Reproductive Techniques (ART), antioxidant and infertility, social health, spiritual health, mental health, Alcohol and drug abuse, preventive factors, and instruments., and selected relevant articles to the study subject from 2004 to 2013. Firstly, a list of 150 papers generated from the initial search. Then reviewers studied titles and abstracts. Secondly, 111 papers were included. Finally, quality assessment of full text studies was performed by two independent reviewers. Researchers reviewed summary of all articles sought, ultimately used data from 62 full articles to compile this review paper. RESULTS: Review of literature led to arrangement of 9 general categories of ART results' relationship with weight watch and diet, exercise and physical activity, psychological health, avoiding medications, alcohol and drugs, preventing diseases, environmental health, spiritual health, social health, and physical health. CONCLUSION: The following was obtained from review of studies: since lifestyle is among important, changeable, and influential factors in fertility, success of these methods can be greatly helped through assessment of lifestyle patterns of infertile couples, and design and implementation of healthy lifestyle counseling programs, before and during implementing assisted fertility techniques. PMID- 26156899 TI - Physical Activity Status and Position of Governmental Employees in Changing Stage Based on the Trans-Theoretical Model in Hamadan, Iran. AB - Physical inactivity is the fourth leading risk factor for death worldwide. Given the key role of employees as valuable human resources and increasing sedentary life style among them, the aim of this study was to evaluate physical activity status and position of governmental employees in changing stage based on the Trans-Theoretical Model (TTM) in Hamadan, Iran, in 2014.This descriptive analytical study was performed on 1200 government employees selected using proportional stratified random sampling. Data collection was performed using a three-section questionnaire containing demographic characteristics, SQUASH (Short questionnaire to assess health-enhancing physical activity) questionnaire and Marcus et al's five-part algoritm. Data were analyzed by multiple linear and logistic regression, Chi-square, T-test and ANOVA using SPSS-20. The mean age of the participants was 38.12+/-8.04 years. About a half of the employees were in the preparatory stage of TTM.49.2% and 50.8% of the sample were classified as active and inactive, respectively .Associations between physical activity status and exercise stage of change were found. The associations between exercise stage of change and age, sex, work experience, education and marital status were significant (p<0.05). Work experience and education were strongly predictors of physical activity (PA) status and accounted for 31.2% of variance in PA (adjusted R2=0.312, R2 change=0.01). The results of this study showed that TTM was useful to evaluate and predict physical activity behavior among the Iranian governmental employees and can be utilized by health planners to inform appropriate intervention strategies, specifically in work place. PMID- 26156900 TI - High Intake of Manganese During Second Trimester, Increases the Risk of Preterm Delivery: A Large Scale Cohort Study. AB - Evidence indicates that nutrients and minerals might play an important role in preterm delivery (PTD). The aim of this study was to determine maternal nutritional status during second trimester of pregnancy and its association with preterm delivery (<34 weeks gestation) in Iranian women. In a large scale longitudinal study, 1033 pregnant women were recruited from prenatal clinics since December 2012 to June 2013. Dietary intake was assessed by Food Frequency Questionnaire (FFQ) in pregnant women of 14 to 20 weeks gestational age. The participants were followed up until delivery. Dietary intake of women with preterm delivery was compared with women who had term delivery. The results show that 61.2% of women were primiparous and that the incidence of preterm delivery was 7%. Manganese dietary intake was significantly higher in mothers with preterm delivery than those with term delivery (P=.03). Manganese was the only micronutrient correlated with preterm delivery after adjustment for maternal characteristics during second trimesters of pregnancy (OR=1.12; P=.01). These results suggest that high maternal manganese dietary intake during the second trimester of pregnancy may be associated with the risk of preterm delivery in Iranian pregnant women. PMID- 26156901 TI - Comparison of Quetiapine and Risperidone in Treatment of Acute Psychosis: A Double-Blind, Randomized-Controlled Study. AB - OBJECTIVE: The aim of this study was to evaluate the effectiveness of Quetiapine versus Risperidone in control of acute psychotic signs and symptoms in hospitalized patients during four weeks. METHODS: In this double-blind, randomized controlled study, a total of 90 patients with a confirmed diagnosis acute psychosis and were hospitalized in Zare Hospital, Sari, Iran, and they were treated with Quetiapine (mean 500 mg/day) or Risperidone (mean 5.2 mg/day), in a 4 week period. The positive and negative symptoms scale (PANSS) and Clinical Global Impression-Severity scale (CGI-s) were used to assess psychotic symptoms and severity of illness in first and the last day of the study. RESULTS: No significant difference found between two groups in decreasing positive and negative sub-scores in the PANSS. Risperidone was superior to Quetiapine in decreasing the PANSS general psychopathology sub-scores and total score (p<0.05). No significant difference found between two groups in decreasing CGI-s score. PMID- 26156902 TI - Determinants of Self-Care in Diabetic Patients Based on Health Belief Model. AB - INTRODUCTION: The aim of this study was to determine self-care predictors in diabetic patients based on health belief model. MATERIALS & METHODS: The cross sectional study was conducted on 110 diabetic patients referred to health service centers in Ardakan city, Yazd, Iran. The data was collected by a questionnaire including perceived benefits, barriers, severity, susceptibility, self-efficacy, social support, self-care behaviors and demographic variables. RESULTS: Regularly medicine use (mean=6.48 times per week) and shoes checking (mean=1.17 times per week) were reported as the highest and the lowest self-care behaviors respectively. Health belief model constructs including perceived benefits, barriers, severity, susceptibility, self-efficacy and social support predicted 33.5% of the observed variance of self-care behaviors. Perceived susceptibility and self-efficacy had positive effect on self-care behavior; whereas perceived barrier's has negative effect. Self-efficacy, perceived susceptibility and barriers were most powerful predictor respectively. CONCLUSION: The findings approved the efficiency of health belief model in prediction of self-care behaviors among diabetic patients. The findings realized the health belief model structure; therefore, it can be used as a framework for designing and implementing educational interventions in diabetes control plans. PMID- 26156903 TI - Learning Organization Profile of Educational Hospitals in Iran: Practice of Organizational Interlocking Systems. AB - BACKGROUND: Organizational learning has been identified as necessary for different organizations to improve their performance in the changing and competitive environment. PURPOSE: The main purpose of this research was to specify the learning organization profile of educational and health centers of Tehran and Qazvin Universities of Medical Sciences in Iran. METHODOLOGY: The present research was conducted using a cross-sectional method in the academic year of 2013-2014. A staff of 530 from educational hospitals subordinated to Tehran and Qazvin universities of medical sciences participated in the research. The participants were selected using stratified random sampling. That is to say, a random sample of a proportionate size was selected from each hospital. The instrument for data collection was a Likert-scale questionnaire involving 50 items. The statistical techniques of ANOVA, t-test, Chi-square, correlation coefficients (Pearson and Spearman), and regression were utilized to analyze the data. All of them were performed using the Statistical Package for Social Sciences (SPSS) 16.0 for windows. RESULT: the results indicated that 449 of participants (84.7%) had a B.S. degree and 78 of them (14.7%) had an M.S. or a Ph.D. degree. Among the fivefold dimensions of "Learning Organization" model (Learning, Organization, People, Knowledge, and Technology) in comparison of the two universities, the "people" dimension was the highest-rated dimension with the mean rating of 25.71+/-8.36 and the "learning" dimension was the lowest-rated dimension with the mean of 25.35+/-8.04. Comparison between the two universities yielded the result that educational hospitals in Tehran University of medical sciences with the rating of 126.56 had a more complete profile than that of educational hospitals in Qazvin university of medical sciences with the rating of 122.23. CONCLUSION: The hospitals of the two above-mentioned universities were, to a great extent, far from the characteristics of Learning Organization. In light of the massive mission of these centers to maintain and improve the community health and to train the skilled labor force, the centers should embark on updating the data and institutionalizing learning. Furthermore, to modify staff's behavior and performance and to achieve their goals, they should accentuate the importance of acquiring, creating, and transferring knowledge. PMID- 26156904 TI - Radiology Reporting System Data Exchange With the Electronic Health Record System: A Case Study in Iran. AB - INTRODUCTION: In order to better designing of electronic health record system in Iran, integration of health information systems based on a common language must be done to interpret and exchange this information with this system is required. BACKGROUND: This study provides a conceptual model of radiology reporting system using unified modeling language. The proposed model can solve the problem of integration this information system with the electronic health record system. By using this model and design its service based, easily connect to electronic health record in Iran and facilitate transfer radiology report data. METHODS: This is a cross-sectional study that was conducted in 2013. The study population was 22 experts that working at the Imaging Center in Imam Khomeini Hospital in Tehran and the sample was accorded with the community. Research tool was a questionnaire that prepared by the researcher to determine the information requirements. Content validity and test-retest method was used to measure validity and reliability of questioner respectively. Data analyzed with average index, using SPSS. Also Visual Paradigm software was used to design a conceptual model. RESULT: Based on the requirements assessment of experts and related texts, administrative, demographic and clinical data and radiological examination results and if the anesthesia procedure performed, anesthesia data suggested as minimum data set for radiology report and based it class diagram designed. Also by identifying radiology reporting system process, use case was drawn. CONCLUSION: According to the application of radiology reports in electronic health record system for diagnosing and managing of clinical problem of the patient, with providing the conceptual Model for radiology reporting system; in order to systematically design it, the problem of data sharing between these systems and electronic health records system would eliminate. PMID- 26156907 TI - Nurse Leaders' Experiences of Implementing Career Advancement Programs for Nurses in Iran. AB - BACKGROUND & PURPOSE: Career advancement programs are currently implemented in many countries. In Iran, the first career advancement program was Nurses' Career Advancement Pathway. The purpose of this study was to explore nurse leaders' experiences about implementing the Nurses' Career Advancement Pathway program in Iran. METHODS: This exploratory qualitative study was conducted in 2013. Sixteen nurse managers were recruited from the teaching hospitals affiliated to Shahid Behesthi, Qazvin, and Iran Universities of Medical Sciences in Iran. Participants were recruited using purposive sampling method. Study data were collected through in-depth semi-structured interviews. The conventional content analysis approach was used for data analysis. RESULTS: participants' experiences about implementing the Nurses' Career Advancement Pathway fell into three main categories including: a) the shortcomings of performance evaluation, b) greater emphasis on point accumulation, c) the advancement-latitude mismatch. CONCLUSION: The Nurses' Career Advancement pathway has several shortcomings regarding both its content and its implementation. Therefore, it is recommended to revise the program. PMID- 26156905 TI - Health-Risk Factors and the Prevalence of Chronic Kidney Disease: Cross-Sectional Findings from a National Cohort of 87,143 Thai Open University Students. AB - BACKGROUND: Chronic kidney disease (CKD) is becoming a major health challenge worldwide as its aetiology has transferred from predominantly infectious disease to emerging chronic diseases, especially diabetes and hypertension. A rapid health-risk transition driven by economic development is transforming Thailand which is now becoming an ageing country where chronic diseases are a major health burden. METHODS: This study used the 2005 baseline cross-sectional dataset of 87,143 Thai Cohort Study members to investigate risk factors associated with CKD. Using multivariate logistic regression, we looked into the relationship between CKD and demographic and socioeconomic factors, personal health status and various health-related behaviours. RESULTS: The prevalence of CKD in men was lower than that in women (2.5% vs 2.7%). In both sexes, CKD is associated with ageing, cigarette smoking and drinking alcohol, having diabetes, high lipids and hypertension. In men, CKD was associated with living in rural areas, having a low income, a higher BMI, short sleeping and having Western fast food. In women, marriage is associated with a higher risk of CKD. CONCLUSIONS: CKD is strongly associated with ageing, underlying diseases, smoking and drinking. Hypertension, elevated lipids, or diabetes are all risk factors that could be prevented or detected and treated. The Ministry of Public Health should encourage Thai people to consume healthy food, maintain a normal weight, stop smoking and drink alcohol in moderation, all of which will help prevent CKD. PMID- 26156906 TI - Factors Influencing Neurosurgeons' Decision to Retain in a Work Location: A Qualitative Study. AB - INTRODUCTION: Physician retention is a serious concern to have an effective and efficient health system; the key challenge is how best to encourage and retain health providers in their work location. There have been considerable studies on factors influencing physicians' retention but little research has been conducted in Iran. This study aims to determine the affecting factors from neurosurgeons' viewpoint to support policy makers in proposing a sort of evidence based retention strategies. METHODS: We conducted semi structured interviews with 17 neurosurgeons working in 9 provinces of Iran between September and November 2014. We included physicians remaining to work in a particular community for at least 3 years and asked them about the factors influenced their decision to retain in a work place. Data were thematically analyzed using "framework approach" for qualitative research. RESULTS: Satisfaction with monetary incentives, availability of adequate clinical infrastructure in a community and appropriate working condition were most commonly cited factors mentioned by all participants as key reasons for retention. Furthermore elements which contributed to the quality of living condition, personal background and incentives, family convenience were emphasized by majority of them. A small number of participants mentioned opportunity for continuing learning and updating knowledge as well as supportive organizational policies as important motivators in a workplace. CONCLUSION: Ministry of Health and Medical Education (MOHME) should consider a multifaceted and holistic approach to improve neurosurgeons' retention in their work location. Our findings suggests a combination of financial remuneration, establishment of adequate hospitals and clinical facilities, collaborative working environment with reasonable workload, proper living condition, family support and facilities for professional development to be employed as an effective strategy for promoting physicians' retention. PMID- 26156908 TI - Do Perceptions of Empowerment Affect Glycemic Control and Self-Care Among Adults with Type 2 Diabetes? AB - BACKGROUND: The Arab adult with T2DM is understudied with less known facts about the perception of empowerment and its relationship with self-care and glycemic control. PURPOSE: The purpose of this study was to determine the extent to which perception of empowerment by Arab adults living with Type 2 Diabetes Mellitus (T2DM) was associated with better glycemic control and self-care management. METHODS: A cross-sectional descriptive study was led among 300 Arab adults living in Oman with T2DM in an outpatient diabetes clinic. The Diabetes Empowerment Scale (DES), glycosylated haemaglobin (HbA1c) and Body mass index was assessed. The DES was found to be valid and reliable for the population. ANOVA, Regression analysis, and Structural equation modeling was used for analysis. RESULTS: The composite score and three subscales of DES were a significant and strong predictor of good glycemic control among Omani adults with T2DM (p<0.001). Age, education, duration of DM, prior DM education program and medications were significantly associated with DES. CONCLUSION: Diabetes nurse educators engaged in the care of adults with T2DM should assess self-empowerment and tailor interventions to increase empowerment for better glycemic control. Patient empowerment plays an essential role in maintaining self-care behaviours and HbA1c. PMID- 26156909 TI - Prevalence of Geographic tongue and Related Predisposing Factors in 7-18 Year-Old Students in Kermanshah, Iran 2014. AB - Geographic tongue is a benign lesion at the dorsum and margins of the tongue that sometimes causes pain and burning sensation. This lesion is characterized by an erythematous area with white or yellow folded edges. The predisposing factors of this lesion include heredity, allergies, psoriasis, stress, fissured tongue and consumption of some foods. The present study was conducted to investigate the prevalence of geographic tongue and its related factors among the 7-18 year-old students in Kermanshah, Iran. This descriptive cross-sectional study was carried out in three schools in Kermanshah using multi-stage random cluster sampling method. A total number of 3600 students were examined (1800 girls and 1800 boys). Demographic data and the results of examinations were recorded in a questionnaire. The factors affecting the incidence of geographic tongue were analyzed by the SPSS-20 software and the Chi-square test.The prevalence of geographic tongue was 7.86% (283 individuals). The incidence of this lesion was significantly higher in males than in females (p<0.01). There was no relationship between geographic tongue and psoriasis or fissured tongue. Pain and discomfort during eating was more prevalent in those with geographic tounge compared to those without this condition (p<0.02). The prevalence of geographic tongue among the studied population was 7.86%, and the prevalence of geographic tongue in male students was higher than in female students. PMID- 26156910 TI - Provider Visits for Asthma: Potential Barriers for Insured Children. AB - OBJECTIVE: The barriers to provider visits for asthma in insured children are not well understood. Our objective was to examine the relationship between parent, family, and child attributes and asthma visits in insured children. METHODS: This retrospective, cross-sectional analysis of 2007 Medical Expenditure Panel Survey Household Component data included insured children 0-17 years old reported to have active asthma. We summed the number of provider visits during which asthma was treated or diagnosed to represent the frequency of asthma visits during the year. Probit models were used to estimate the relationship between parent, family, and child attributes and asthma visits. RESULTS: Seventy percent of the 542 children did not have an asthma visit during the year. Children with parents employed full time were 16 percentage points less likely to have an asthma visit than children whose parents were not working (P=.01). CONCLUSION: Many insured children go more than a year without seeing a provider for their asthma, signaling that insurance is not sufficient to guarantee children will receive asthma monitoring. The attributes related to asthma visits suggest potential barriers that providers might want to consider to increase participation in asthma visits. PMID- 26156911 TI - Comparison of the Effect of Anesthesia With Midazolam-Fentanyl Versus Propofol Remifentanil on Bispectral Index in Patients Undergoing Coronary Artery Bypass Graft. AB - The aim of this study was to compare the effect of anesthesia with midazolam fentanyl versus propofol-remifentanil on the BIS (bispectral index) in patients undergoing coronary artery bypass grafting (CABG). Sixty-four patients undergoing CABG were randomly assigned to one of two study groups: midazolam-fentanyl (MF, N=32) or propofol-remifentanil (PR, N=32). The BIS was measured before induction of anesthesia, five minutes after induction of anesthesia, at skin incision, sternotomy, pericardiotomy, aorta cannulation, onset of cardiopulmonary bypass, during rewarming, five minutes after separation from cardiopulmonary bypass, at thorax closure, and at the end of the surgery. There were no significant differences between the two groups with regard to age and gender. The difference in mean BIS between the two groups was significant (P<0.05) at all times, except before induction, five minutes after induction, at skin incision and on rewarming. Changes in the BIS were lower in the PR group than in the MF group. Both techniques can provide adequate anesthesia in patients undergoing CABG. However, the probability of awareness during anesthesia is lower with propofol remifentanil than with midazolam-fentanyl. PMID- 26156912 TI - Nurses, the Oppressed Oppressors: A Qualitative Study. AB - Healthcare equity, defined as rightful and fair care provision, is a key objective in all health systems. Nurses commonly experience cases of equity/inequity when caring for patients. The present study was the first to explain nurses' experience of equal care. A qualitative study sought to describe the experiences of 18 clinical nurses and nurse managers who were selected through purposive sampling. The inclusion criteria were the nurses' familiarity with the subject of the study and willingness to participate. The data were collected through in-depth, unstructured, face-to-face interviews. The sampling continued up to data saturation. All the interviews were recorded and then transcribed word by word. The data were analyzed using thematic analysis. The major theme extracted in this study was the equation between submissiveness and oppression in nurses. It had two subthemes, namely the oppressed nurse and the oppressive nurse. The first subtheme comprised three categories including nurses' occupational dissatisfaction, discrimination between nursing personnel, and favoring physicians over nurses. The second subtheme consisted of three categories, namely habit-oriented care provision, inappropriate care delegation, and care rationing while neglecting patient needs. When equal care provision was concerned, the participating nurses fluctuated between states of oppression and submissiveness. Hence, equal conditions for nurses are essential to equal care provision. In fact, fair behavior toward nurses would lead to equity nursing care provision and increase satisfaction with the healthcare system. PMID- 26156913 TI - Quality of Life in Patients Undergoing Percutaneous Transluminal Coronary Angioplasty (PTCA). AB - BACKGROUND: Coronary artery diseases are the main causes of death in industrial Countries. Transluminal angioplasty is a common technique used to manage the condition of coronary arteries. The purpose of this study was to explore the quality of life in patients sustaining this measure in two stages before the procedure and then three consecutive after that 3, 6 and 12 months respectively. MATERIALS & METHODS: This research was a longitudinal study and data was collected between 2011-2013 years. 115 patients were included. Data were collected through using a questionnaire with 40 questions. The subjects before, 3, 6 and 12 months after the procedure filled out questioner. Data were analyzed by statistical tests including T-test, Fisher exact test, Wilcoxon and Friedman with Software SPSS version 16, P value<0.05. RESULTS: There were significant differences in the quality of life in patients with PTCA before procedure and 3 months after that (P=0.004). Quality of life of patients undergoing PTCA in the four levels, three, six and twelve months after the operation had a significant difference (P<0.001). CONCLUSIONS: Quality of life of people with PTCA operation three months after surgery is reduced. It is required during this period the patient treatment team and supports his family and put under the necessary training in this period to give patients and encourage them to pursue their condition should. PMID- 26156914 TI - Assessing the Awareness of Agents Involved in Issuance of Death Certificates About Death Registration Rules in Iran. AB - INTRODUCTION: In the death registration system, issuance of death certificate, as a binding rule, is considered among the major necessities of preparation of death statistics. In order to prepare death statistics that are adequately valid for subsequent applications, it is necessary to properly encode death certificates and fully follow rules on causes underlying death. This study aimed to assess the awareness and performance of agents involved in issuance of death certificate in the national death records system. METHODS: It was a descriptive cross-sectional research, which was performed from September 2013 to March 2014 on 96 agents involved in issuance of death certificate Imam Khomeini, Alavi, Fatemi and BuAli education and treatment centers of Ardebil University of Medical Sciences. The population included faculty staff physicians, residents and health information management staffs. The research scale was also a researcher-made questionnaire that questioned the demographic information as well as awareness and performance of participants regarding death certificate coding rules. Research data was analyzed based on descriptive statistics and the chi-square test method in the SPSS software at a confidence level of 95%. FINDINGS: A total of 34.42% of participants were aware of the general rules on issuance of death certificates while faculty staff higher specialists (41.67%) and clinical coders (38.34%) with five years of experience demonstrated the highest awareness levels. Only 23 participants (24.6%) were trained to issue death certificates. A total of 76 participants (79.3%) announced their need for learning how to complete death certificate forms on a constant basis. The awareness of participants about the general principle was assessed to be low (30.25%). Moreover, their awareness of selection rules and modification rules was low (27.75%) and moderate (45.25%), respectively. The chi-square test revealed a significant relationship between work experience and awareness of participants about coding rules (P=0.001), but no significant relationship was observed between education and awareness of coding rules (P=0.497). CONCLUSION: The awareness of participants about rules on coding death causes and their performance in this field was so satisfactory. That is to say, the awareness of faculty staff and health information management staffs was unexpectedly low. Seemingly, lack of adequate training is an international issue that causes mistakes in the recording of information on mortality. Hence, a short-term solution is to train faculty staff and residents and also revise the training provided to health information management staffs. As a long-term solution it is possible to provide related courses to general practitioner students. PMID- 26156915 TI - Dental Students' Educational Achievement in Relation to Their Learning Styles: A Cross-Sectional Study in Iran. AB - BACKGROUND & OBJECTIVES: In recent decades, many studies have been carried out on the importance of Kolb experiential learning theory (ELT) in teaching-learning processes and its effect on learning outcomes. However, some experts have criticized the Kolb theory and argue that there are some ambiguities on the validity of the theory as an important predictor of achievement. This study has been carried out on dental students' educational achievement in relation to their dominant learning styles based on Kolb theory in Mashhad University of Medical Sciences (Iran). METHODS: In a cross sectional study, Kolb Learning Style Inventory (LSI Ver. 3.1) as well as a questionnaire containing students' demographic data, academic achievement marks including grade point average (GPA), theoretical and practical courses marks, and the comprehensive basic sciences exam (CBSE) scores were administered on a purposive sample of 162 dental students who had passed their comprehensive basic sciences exam. Educational achievement data were analyzed in relation to students' dominant learning styles, using descriptive and analytical statistics including chi2, Kruskal-Wallis and two-way ANOVA tests. RESULTS: The dominant learning styles of students were Assimilating (53.1%), Converging (24.1%), Diverging (14.2%) and Accommodating (8.6%). Although, the students with Assimilating and Converging learning styles had a better performance on their educational achievement, there was no significant relationship between educational achievement and dominant learning style (P>=0.05). CONCLUSION: Findings support that the dominant learning style is not exclusively an essential factor to predict educational achievement. Rather, it shows learning preferences of students that may be considered in designing learning opportunities by the teachers. PMID- 26156916 TI - Undergraduate Medical Research Programme: A Cross-Sectional Study of Students' Satisfactions, Perceived Challenges, and Attitudes. AB - BACKGROUND: Implementing an undergraduate Medical Research Programme (MRP) in medical colleges may not only improve the subsequent career of medical students but also benefit the health system in general. If not designed effectively, however, such a programme could have the opposite impact. Therefore, the quality of a MRP should be evaluated continuously. This study aims to evaluate the MRP from medical students' perspective. METHODS: A cross-sectional survey study was conducted from March to April 2014 amongst undergraduate medical students at the College of Medicine, King Saud University for Health Sciences, Riyadh, Saudi Arabia. Satisfaction, perceived challenges, and attitudes towards the MRP were evaluated. RESULTS: A total of 154 responses were collected from the students; 81(52.6%) were in the 2nd year and 73 (47.4%) were in the 3rd year of the MRP, 97(63%) were males. The mean+/-SD age was 21.5+/-0.82 years. Overall, most students were satisfied with the MRP (51.3%). The majority of students were of the opinion that there was a shortage of time to complete their work (57.6%) and a lack of motivation to do research (53.3%). Significant differences were found in the satisfaction levels and perceived challenges between students in the 2nd and 3rd year of the MRP (P<=.013). DISCUSSION: Assessment of medical students' perspective towards the MRP is an important aspect of the educative process. We recommend more evaluation studies, because they ensure that programmes effectively meet their goals and continue to be improved. A solid MRP is essential and will increase the university's profile. PMID- 26156917 TI - A Case of Tuberous Sclerosis Without Multiorgan Involvement. AB - Tuberous sclerosis or Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant and progressive neurocutaneous disorder involves multiple organs mainly brain, heart, kidney, lung, liver, skin and eye. The diagnosis is typically made clinically. Here, we are reporting a case of TSC presented mainly with dermatologic findings and only neurologic manifestations on MRI. A 15-year old female with intellectual disability is followed up at neurology clinic for history of seizure. Intelligence evaluation showed that she has intellectual disability. She had wart like lesions distributed in form of butterfly over the face especially involving nose. She did not have any sign and symptom of heart, kidney, lung, bone and eye involvement. Also, her laboratory tests were normal. Despite the physical examination showed absolutely intact neurologic examination, but brain MRI and CT scan revealed several cortical and subcortical tubers, and subependymal glial nodules; no evidence of giant cell astrocytomas and aneurysm. Hypesignal foci are seen at subcortical white matter on long TR images. Fibers are involved. In this case, there is no evidence of giant cell astrocytomas and aneurysm. It seems that TSC could be the prevalent disorder and referring intellectual disability patients in birth with normal organs could be diagnosed as TSC. Therefore, there is necessary need to design genetic natal and post natal tests for diagnosis of TSC cases. Also, there is pivotal that similar cases must be reported; perhaps TSC is more prevalent than to be considered. PMID- 26156918 TI - What Really Motivates Iranian Nurses to Be Creative in Clinical Settings?: A Qualitative Study. AB - BACKGROUND: Creativity and innovation are key elements for organization improvement, particularly in nursing, and for finding alternatives for solving nurses' occupational problems. Nurses' creativity is affected by motivation. Although, there are many possible sources of motivation, the Iranian nurses' creativity is seldom clarified, and the most important factors motivating nurses to be creative in clinical settings has rarely been addressed. OBJECTIVES: The aim of this study was to explore Iranian nurses' experiences regarding the most important factors that motivate their creativity in clinical settings. METHODS: This qualitative study was conducted using conventional content analysis approach. A purposive sample of sixteen nurses was recruited from two educational hospitals affiliated to Tehran and Jahrom Universities of Medical Sciences in Iran. Data were gathered through conducting face-to-face semi-structured interviews and were analyzed by qualitative content analysis approach. FINDINGS: Five main themes emerged from the data analysis, including: (a) Intrinsic motivators, (b) Extrinsic motivators, (c) Achievement motivators, (d) Relational or altruistic motivators, and (e) Spiritual motivators. CONCLUSIONS: Study findings indicated that nurses are creative and innovative individuals. So nurse managers and health policy makers should consider creativity as an integral part of all health and clinical strategies and policies. They should support creative and innovative efforts of nurses and provide a climate in which nurses engage in more creative and productive behaviors. PMID- 26156919 TI - Cognitive factors related to drug abuse among a sample of Iranian male medical college students. AB - BACKGROUNDS: Drug abuse is one of the most serious social problems in many countries. College students, particularly at their first year of education, are considered as one of the at risk groups for drug abuse. The present study aimed to determine cognitive factors related to drug abuse among a sample of Iranian male medical college students based on the social cognitive theory (SCT). METHOD: This cross-sectional study was carried out on 425 Iranian male medical college students who were randomly selected to participate voluntarily in the study. The participants filled out a self-administered questionnaire. Data were analyzed by the SPSS software (ver. 21.0) using bivariate correlations, logistic and linear regression at 95% significant level. RESULTS: Attitude, outcome expectation, outcome expectancies, subjective norms, and self-control were cognitive factors that accounted for 49% of the variation in the outcome measure of the intention to abuse drugs. Logistic regression showed that attitude (OR=1.062), outcome expectancies (OR=1.115), and subjective norms (OR=1.269) were the most influential predictors for drug abuse. CONCLUSIONS: The findings suggest that designing and implementation of educational programs may be useful to increase negative attitude, outcome expectancies, and subjective norms towards drug abuse for college students in order to prevent drug abuse. PMID- 26156920 TI - Fairness of Financial Contribution in Iranian Health System: Trend Analysis of National Household Income and Expenditure, 2003-2010. AB - BACKGROUND: Social systems are dealing with the challenge of achieving fairness in the distribution of financial burden and protecting the risk of financial loss. The purpose of this paper is to present a trend analysis for the indicators related to fairness in healthcare's financial burden in rural and urban population of Iran during the eight years period of 2003 to 2010. METHODS: We used the information gathered by statistical center of Iran through sampling processes for the household income and expenditures. The indicators of fairness in financial contribution of healthcare were calculated based on the WHO recommended methodology. The indices trend analysis of eight-year period for the rural, urban areas and the country level were computed. RESULTS: This study shows that in Iran the fairness of financial contribution index during the eight-year period has been decreased from 0.841 in 2003 to above 0.827 in 2010 and The percentage of people with catastrophic health expenditures has been increased from 2.3% to above 3.1%. The ratio of total treatment costs to the household overall capacity to pay has been increased from 0.055 to 0.068 and from 0.072 to 0.0818 in urban and rural areas respectively. CONCLUSION: There is a decline in fairness of financial contribution index during the study period. While, a trend stability of the proportion of households who suffered catastrophic health expenditures was found. PMID- 26156921 TI - Green Tea Gargling Effect on Cough & Hoarseness After Coronary Artery Bypass Graft. AB - INTRODUCTION: Endotracheal intubation is a method necessary for controlling and maintaining airway during general anesthesia. Cough and hoarseness are common complications after endotracheal intubation. Inflammation has an important role in postoperative cough and hoarseness outbreak. Also it has been stated that green tea has anti-inflammatory properties. Therefore, the current study has been conducted to investigate green tea gargling solution effect on cough and hoarseness after coronary artery bypass graft (CABG) surgery. METHODS: In this single-blind, randomized, & controlled clinical trial, we enrolled 121 patients undergoing CABG admitted to the ICU. The intervention group participants were asked to gargle 30 cc of green tea solution. The control group patients gargled 30 cc of distilled water. An hour after extubation, the intervention group patients were asked to gargle 30 cc of green tea and the control group patients were required to gargle 30 cc of distilled water every 6 hour up to 24 hour (each patient for 4 times). Moreover, the cough and hoarseness questionnaire was also filled in 6, 12, and 24 hours after endotracheal extubation. RESULTS: The results showed no significant differences among the patients in both groups regarding age, gender, body mass index, smoking history, and anesthesia duration. There was a significant difference between the two groups in terms of cough 12 hours after removing the endotracheal tube. At other times, there was no significant difference between the two groups considering cough and hoarseness. CONCLUSION: The present study results showed that green tea gargling does not decrease hoarseness. Though, cough occurrence was less in the intervention group than the other group. PMID- 26156922 TI - Body Weight Reduction Results in Favorable Changes in Blood Pressure, Serum Lipids, and Blood Sugar in Middle-Aged Japanese Persons: A 5-Year Interval Observational Study of 26,824 Cases. AB - OBJECTIVE: We investigated the relationships between body weight (BWt) and metabolic syndrome (MS) risk factors to elucidate the effect of BWt (?BWt) change and body mass index (BMI) on these factors in the Japanese population. METHODS: Data were collected on MS-related parameters measured during two annual examinations of 16,640 men (mean age: 41.7+/-11.6 years) and 10,184 women (mean age: 45.0+/-12.2 years) without prior treatment of hypertension, diabetes mellitus, or dyslipidemia in 2006 and 2011 in Fukuoka, Japan. The subjects were divided into three groups according to BMI in 2006 (low, middle and high BMI) and into three groups according to change in BMI between 2006 and 2011 (decreased, stable, and increased BMI). Mean values for blood pressure (BP), systolic BP (SBP), diastolic BP (DBP), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), hemoglobin A1c (HbA1c), and fasting blood glucose (FBG) for each group were determined by sex and subjected to statistical analysis for comparison. RESULTS: High BMI (>26) was associated with higher SBP, LDL-C, FBG, and TG in both sexes. An increase>=1.1 BMI units in 5 years was associated with increased DBP, LDL-C, TG, HbA1c, and FBG and decreased HDL-C. In contrast, decreased BMI was associated with decreased BP and LDL-C and increased HDL-C in both sexes, and decreased TG in men and FBG in women. CONCLUSIONS: Maintaining a desirable weight or losing weight may help prevent hypertension and MS, even in non-obese individuals. PMID- 26156923 TI - Community Interventions to Improve Glycemic Control in African Americans with Type 2 Diabetes: A Systemic Review. AB - PURPOSE: The purpose of this study was to conduct a systematic review of published community interventions to evaluate different components of community interventions and their ability to positively impact glycemic control in African Americans with T2DM. METHODS: Medline, PsychInfo, and CINAHL were searched for potentially eligible studies published from January 2000 through January 2012. The following inclusion criteria were established for publications: (1) describe a community intervention, not prevention; (2) specifically indicate, in data analysis and results, the impact of the community intervention on African American adults, 18 years and older; (3) measure glycemic control (HbA1C) as an outcome measure; and (4) involve patients in a community setting, which excludes hospitals and hospital clinics. RESULTS: Thirteen studies out of 9,233 articles identified in the search met the predetermined inclusion criteria. There were 5 randomized control trials and 3 reported improved glycemic control in the intervention group compared to the control group at the completion of the study. Of the 8 studies that were not randomized control trials, 6 showed a statistically significant change in HbA1C. CONCLUSION: In general, the community interventions assessed led to significant reductions in HbA1C in African Americans with type 2 diabetes. Community health workers did not have a greater impact on glycemic control in this sample. The findings of this study provides insight for designing community-based interventions in the future, such as including use of multiple delivery methods, consideration of mobile device software, nutritionist educator, and curriculum-based approaches. PMID- 26156924 TI - The Impact of Cognitive, Social and Physical Limitations on Income in Community Dwelling Adults With Chronic Medical and Mental Disorders. AB - INTRODUCTION: As much as 45% of the US population has at least one chronic condition while 21% have multiple chronic diseases. The study examined the impact of cognitive, social and physical limitations on the personal income of U.S. adults with seven chronic diseases. METHODS: A cross-sectional analysis of 19,357 US adults with seven chronic diseases (diabetes, hypertension, heart disease, stroke, depression, emphysema and joint disease) from the 2006 Medical Expenditure Panel Survey (MEPS) was performed. The effect of seven chronic diseases and their associated cognitive, social, and physical limitations on personal income was assessed using a two-stage Heckman model. RESULTS: Depression emerged as the only chronic disease that was independently associated with a significant $1,914 decrease in personal income (95% CI -$2,938--$890). Social and cognitive limitations resulted in $1,944 (95% CI -$3,378--$511) and $3,039 (95% CI -$4,418-$1,659) decreases in personal incomes respectively while physical limitations did not result in a statistically significant reduction. Being Non Hispanic Black, Hispanic, Other Race, female, never married, married, less than a bachelor's degree, publicly insured, uninsured, or having a health status less than very good were also associated with significant reductions in personal income. CONCLUSIONS: The findings of this study suggest a need to determine the specific limitations associated with common chronic diseases and identify appropriate compensatory strategies to reduce their impact on income. PMID- 26156925 TI - Reengineering NHS Hospitals in Greece: Redistribution Leads to Rational Mergers. AB - The purpose of this study was to record and evaluate existing public hospital infrastructure of the National Health System (NHS), in terms of clinics and laboratories, as well as the healthcare workforce in each of these units and in every health region in Greece, in an attempt to optimize the allocation of these resources. An extensive analysis of raw data according to supply and performance indicators was performed to serve as a solid and objective scientific baseline for the proposed reengineering of the Greek public hospitals. Suggestions for "reshuffling" clinics and diagnostic laboratories, and their personnel, were made by using a best versus worst outcome indicator approach at a regional and national level. This study is expected to contribute to the academic debate about the gap between theory and evidence based decision-making in health policy. PMID- 26156926 TI - Iranian Nurses' Views on Barriers and Facilitators in Patient Education: A Cross Sectional Study. AB - BACKGROUND: As a major factor in patient-centered care, patient education has a great impact on the quality of care provided by nurses; however, clinical nurses' performance with regard to patient education is not satisfactory. This study is an attempt to investigate barriers and facilitators in patient education from nurses' point of view. METHODS: 122 nurses at Jahrom University of Medical Sciences participated in this descriptive-cross sectional study. Sampling was based on the census method. The questionnaire used to collect data included questions about nurses' demography, barriers (10 questions), and facilitators (10 questions) in patient education. The questionnaire was designed to be completed independently. To analyze the data, the researchers used descriptive statistics, including frequency, mean and standard deviation. RESULTS: The highest scores related to barriers to patient education were: nurses' insufficient knowledge, patients' physical and emotional unpreparedness, and lack of a proper environment for education. The most important facilitators, on the other hand, were: enhancement of instructing nurses' knowledge and skills, motivating nurses, and a step-by-step approach to patient education. CONCLUSION: It is important that nurses be prepared and motivated to train their patients. By satisfactory patient education on the part of nurses, patients will be more willing to cooperate in the treatment process. PMID- 26156927 TI - Assessment of Clinical Risk Management System in Hospitals: An Approach for Quality Improvement. AB - BACKGROUND: Clinical risks have created major problems in healthcare system such as serious adverse effects on patient safety and enhancing the financial burden for the healthcare. Thus, clinical risk management (CRM) system has been introduced for improving the quality and safety of services to health care. The aim of this study was to assess the status of CRM in the hospitals. METHODS: A cross-sectional study was conducted on 200 nursing staff from three teaching hospitals affiliated with the Kerman University of Medical Sciences in southeast of Iran. Data were collected from the participants using questionnaire and observational checklist in quality improvement offices and selected wards. The data were analyzed using SPSS version 20. RESULTS: Almost, 57% of persons participated in at least one of training sessions on CRM. The status of CRM system was rated from weak to moderate (2.93+/-0.72- 3.18+/-0.66). Among the six domains of CRM system, the highest mean belonged to domain the monitoring of analysis, evaluation and risk control (3.18+/-0.72); the lowest mean belonged to domain the staff's knowledge, recognition and understanding of CRM (2.93+/-0.66). There were no integrated electronic systems for recording and analyzing clinical risks and incidents in the hospitals. CONCLUSION: Attempts have been made to establish CRM through improvement quality approach such as clinical governance and accreditation, but not enough, however, health care should move toward quality improvement and safe practice through the effective integration of CRM in organizational process. PMID- 26156928 TI - Type 2 Diabetes Mellitus Screening and Risk Factors Using Decision Tree: Results of Data Mining. AB - OBJECTIVES: The aim of this study was to examine a predictive model using features related to the diabetes type 2 risk factors. METHODS: The data were obtained from a database in a diabetes control system in Tabriz, Iran. The data included all people referred for diabetes screening between 2009 and 2011. The features considered as "Inputs" were: age, sex, systolic and diastolic blood pressure, family history of diabetes, and body mass index (BMI). Moreover, we used diagnosis as "Class". We applied the "Decision Tree" technique and "J48" algorithm in the WEKA (3.6.10 version) software to develop the model. RESULTS: After data preprocessing and preparation, we used 22,398 records for data mining. The model precision to identify patients was 0.717. The age factor was placed in the root node of the tree as a result of higher information gain. The ROC curve indicates the model function in identification of patients and those individuals who are healthy. The curve indicates high capability of the model, especially in identification of the healthy persons. CONCLUSIONS: We developed a model using the decision tree for screening T2DM which did not require laboratory tests for T2DM diagnosis. PMID- 26156929 TI - The Frequency of Enterobius Vermicularis Infections in Patients Diagnosed With Acute Appendicitis in Pakistan. AB - INTRODUCTION: The main aim of this study was to determine the frequency of Enterobius vermicularis infections and other unique histopathological findings in patients diagnosed with acute appendicitis. MATERIALS: This retrospective study was conducted in a tertiary care hospital of Karachi, Pakistan over a time period of 9 years from 2005 to 2013. The recorded demographic and histopathological data for the 2956 appendectomies performed during this time frame were extracted using a structured template form. Negative and incidental appendectomies were excluded from the study. RESULTS: Out of the 2956 patients diagnosed with acute appendicitis, 84 (2.8%) patients had Enterobius vermicularis infections. Malignancy (n=2, 0.1%) and infection with Ascaris (n=1, 0.1%) was found very rarely among the patients.Eggs in lumen (n=22, 0.7%), mucinous cystadenoma (n=28, 1.0%), mucocele (n=11, 0.4%), lymphoma (n=9, 0.3%), obstruction in lumen (n=17, 0.6%) and purulent exudate (n=37, 1.3%) were also seldom seen in the histopathological reports. CONCLUSION: Enterobius vermicularis manifestation is a rare overall but a leading parasitic cause of appendicitis. Steps such as early diagnosis and regular de worming may help eradicate the need for surgeries. PMID- 26156930 TI - Measurement of Entrance Skin Dose and Calculation of Effective Dose for Common Diagnostic X-Ray Examinations in Kashan, Iran. AB - The knowledge of the radiation dose received by the patient during the radiological examination is essential to prevent risks of exposures. The aim of this work is to study patient doses for common diagnostic radiographic examinations in hospitals affiliated to Kashan University of Medical sciences, Iran. The results of this survey are compared with those published by some national and international values. Entrance surface dose (ESD) was measured based on the exposure parameters used for the actual examination and effective dose (ED) was calculated by use of conversion coefficients calculated by Monte Carlo methods. The mean entrance surface dose and effective dose for examinations of the chest (PA, Lat), abdomen (AP), pelvis (AP), lumbar spine (AP, Lat) and skull (AP, Lat) are 0.37, 0.99, 2.01, 1.76, 2.18, 5.36, 1.39 and 1.01 mGy, and 0.04, 0.1, 0.28, 0,28, 0.23, 0.13, 0.01 and 0.01 mSv, respectively. The ESDs and EDs reported in this study, except for examinations of the chest, are generally lower than comparable reference dose values published in the literature. On the basis of the results obtained in this study can conclude that use of newer equipment and use of the proper radiological parameter can significantly reduce the absorbed dose. It is recommended that radiological parameter in chest examinations be revised. PMID- 26156931 TI - Assessing the Factors Associated With Iran's Intra-Industry Trade in Pharmaceuticals. AB - BACKGROUND: Pharmaceutical industry is a sensitive and profitable industry. If this industry wants to survive, it should be able to compete well in international markets. So, study of Iran's intra-industry trade (IIT) in pharmaceuticals is essential in order to identify competitiveness potential of country and boost export capability in the global arena. METHODS: This study assessed the factors associated with Iran's intra-industry trade in pharmaceuticals with the rest of the world during the 2001-2012 periods using seasonal time series data at the four-digit SITC level. The data was collected from Iran's pharmaceutical Statistics, World Bank and International Trade Center. Finally, we discussed a number of important policy recommendations to increase Iran's IIT in pharmaceuticals. RESULTS: The findings indicated that economies of scale, market structure and degree of economic development had a significantly positive impact on Iran's intra-industry trade in pharmaceuticals and tariff trade barriers were negatively related to IIT. Product differentiation and technological advancement didn't have the expected signs. In addition, we found that Iran's IIT in pharmaceuticals have shown an increasing trend during the study period. Thus, the composition of Iran trade in pharmaceuticals has changed from inter-industry trade to intra-industry trade. CONCLUSIONS: In order to get more prepared for integration into the global economy, the development of Iran's IIT in pharmaceuticals should be given priority. Therefore, paying attention to IIT could have an important role in serving pharmaceutical companies in relation to pharmaceutical trade. PMID- 26156932 TI - Self-Esteem Among the Elderly Visiting the Healthcare Centers in Kermanshah-Iran (2012). AB - BACKGROUND & OBJECTIVE: Self-esteem is viewed the most decisive factor in the psychological development of the elderly. This study was performed to assess self esteem among the elderly referring to the elderly consulting unit of the healthcare centers in Kermanshah, Iran. METHODS: A cross-sectional study was completed with 201 elderly respondents visiting the consulting unit of the healthcare services in Kermanshah, Iran. The samples were selected through convenience sampling. Rosenberg Self-esteem Scale (RSC) was used to gather the required data. Data were analyzed by using both descriptive (frequency, mean, median and standard deviation) and inferential statistics (chi-square and independent t-test). RESULTS: The findings showed a mean of 35.63+/-5.25 for self esteem, indicating a high level of self-esteem (66.2%) among the elderly. A statistically significant difference was reported between the mean of self-esteem and career (p<0.001), marital status (p<0.04), history of health problems (p<0.04), residence (p<0.001), education (p<0.001) and income (p<0.001). CONCLUSION: The findings of this study indicated that approximately one third of the elderly had a low self-esteem, which is indicative of the need to promote the self-esteem of the elderly in order to reduce their physical, psychological and social problems. Thus, it is necessary for the healthcare authorities to provide the elderly with financial, social and psychological support. PMID- 26156933 TI - Evaluation of an Assertive Continuing Care Program for Hispanic Adolescents. AB - PURPOSE: This study evaluated an Adolescent Community Reinforcement Approach (A CRA) and Assertive Continuing Care (ACC) program targeting Hispanic adolescents at risk for substance abuse. METHOD: The Clinic for Education, Treatment, and Prevention of Addiction (CETPA, Inc.), a behavioral health provider offering culturally appropriate substance use and mental health services, carried out the intervention. We examined longitudinal substance use data in relation to time spent in the program and possible confounders. RESULTS: We analyzed data from 72 adolescent clients collected between 2010 and 2012. Self-reported data were evaluated to determine if time spent in the program was associated with substance use reduction. The data were correlated, zero-inflated, and overdispersed; consequently, we employed a mixed-effects zero-inflated negative-binomial model. Time spent in CETPA's program was significantly associated with reductions in the number of days of substance use (p=.039), but not with the likelihood of fully abstaining from use (p=.290). For non-abstinent participants who spend a year in the program, our models revealed an average decline of 46% in reported days of substance use. CONCLUSIONS: A culturally tailored and age-appropriate substance abuse program for Hispanic adolescents resulted in a significant reduction of the numbers of days using alcohol, drugs, or other illicit substances. The A-CRA/ACC approach can yield successful results in culturally diverse settings. PMID- 26156934 TI - General Health Among Parents Who Lost Their Children in the Bam Earthquake. AB - AIM: Bam earthquake and its profound tragedy of thousands killed has caused emotional and psychological trauma for tens of thousands of people who have survived. This study aimed to investigate general health of parents who lose their children in Bam earthquake 10 years after the earthquake. METHOD: General health of 166 parents who lost their children in Bam earthquake was assessed using a translated version of General Health Questionnarie-28 items. RESULTS: The mean score of GHQ was 25.63+/-15.28. Among all domains, the higher mean score belonged to the category of "anxiety/insomnia" and the lower one belonged to the category of "severe depression". The results revealed significant correlation between total GHQ mean score and gender as well as educational level (0.003). CONCLUSION: Providing reflective narrative environments in which survivors can express their own experiences and feelings about earthquake, their loss and how they cope with it seems to be as an effective approach to identify their psychosocial situation and its influential factors. In such narrative environments special attention should be given to older participants, females and those who are single. PMID- 26156935 TI - Sharp Injuries Among Medical Students. AB - INTRODUCTION: Sharp injuries threaten the health of healthcare employees. They cause the transmission of many diseases such as hepatitis B and C, AIDS, etc., which can increase the associated costs associated with them. The aim of this study was to investigate the frequency of sharp injuries among the students of Hormozgan University of Medical Sciences. METHOD: This cross-sectional study was conducted during 2012-2013 in Hormozgan University of Medical Sciences, IR Iran. The target population consisted of the medical, nursing, midwifery, operating room technician, and medical laboratory students in the 2012-2013 academic year. Census sampling was conducted, and accordingly, 500 students participated in the study Data was collected using modified questionnaire of the University of San Diego's injury report form. The collected data were entered into SPSS V.19 and analyzed using descriptive statistical tests. FINDINGS: Finally 377 students (75.4%) returned the questionnaire. Among the studied students, 184 students (39.3%) had had sharp injuries. The frequency of damaging Vein puncture was the most common mechanism of injury DISCUSSION & CONCLUSION: The prevalence of sharp injuries is high among students which can increase the risk of disease and its subsequent risks, and thus, increase the cost and stress among students. It seems that holding workshops and increasing students' awareness and skills to face these risks can be effective in mitigating them. PMID- 26156936 TI - Perception of the Image of a Child and Oneself in the Role of a Mother by Women Parenting Disabled Children. AB - The article discusses the role of the parent-child interaction in the development of a young child with disabilities. It mentions possible distortions of the said interaction. In addition, the submitted material contains the results of an empirical study on the structure and content of the image of a child and perception of oneself in the role of a mother by women parenting children with disabilities. PMID- 26156937 TI - Knowledge, Attitude and Practice of Carrier Thalassemia Marriage Volunteer in Prevention of Major Thalassemia. AB - INTRODUCTION: Thalassemia is the most common genetic disorder and rising in the world as a health problem. Due to the criticality of this disease, in our country thalassemia prevention programs are more importance. The aim of this study was investigation of knowledge, attitude and behavior of marrying partners who were thalassemia genetic carriers in prevention of the birth of the children with major thalassemia. METHODS: This study was a descriptive-analytic study. Data collection tool was a self-administered questionnaire that included 43 items. The content validity of questionnaire was investigated under the supervision of physicians, experts of health education and promotion. Its reliability was confirmed by Cronbach's Alpha test. The subjects in the study consisted of 100 marrying partners who were genetic carriers of thalassemia who referred to Premarital Counseling Center in Iranshahr City. Iranshahr is a a large city of Sistan and Balouchestan Province that located in southeast of Iran. The subjects were selected by convenience non-probability sampling method. Data analyzed using descriptive and analytic statistical tests in SPSS 16.00 and level of significance considered on alpha<0.05. FINDINGS: The average age of men and women that participated in this study was 21.92 and 24 years respectively. 88% of the partners had familial relationships. The educational level of most of the men (34%) was diploma and of women (44%) was pre-diploma. The research findings showed that 7% and 62% of the subjects had poor and mediocre levels of knowledge respectively. Also results showed that only 13% of them had a satisfactory behavior and educational status had a positive correlation with knowledge, behavior, perceived susceptibility and perceived severity (P<0.05). As well there was a significant statistical relationship between gender and familial relationship, and the perceived barriers of participants. (p=0.01). The survey viewpoint of participants showed that they believed knowledge increasing (40%), genetic counseling (33%) and premarital screening (27%) were the most important strategies for prevention of thalassemia. CONCLUSION: The perceived barriers were the strongest predictors for preventive behaviors of incidence of major thalassemia in marrying partners, therefor educational interventions should focused on perceived barriers removing in Volunteer marrying partners. PMID- 26156938 TI - Transdiagnostic dimensions of anxiety: Neural mechanisms, executive functions, and new directions. AB - Converging neuroscientific and psychological evidence points to several transdiagnostic factors that cut across DSM-defined disorders, which both affect and are affected by executive dysfunction. Two of these factors, anxious apprehension and anxious arousal, have helped bridge the gap between psychological and neurobiological models of anxiety. The present integration of diverse findings advances an understanding of the relationships between these transdiagnostic anxiety dimensions, their interactions with each other and executive function, and their neural mechanisms. Additionally, a discussion is provided concerning how these constructs fit within the Research Domain Criteria (RDoC) matrix developed by the National Institutes of Mental Health and how they relate to other anxiety constructs studied with different methods and at other units of analysis. Suggestions for future research are offered, including how to (1) improve measurement and delineation of these constructs, (2) use new neuroimaging methods and theoretical approaches of how the brain functions to build neural mechanistic models of these constructs, and (3) advance understanding of the relationships of these constructs to diverse emotional phenomena and executive functions. PMID- 26156939 TI - Selective looking at natural scenes: Hedonic content and gender. AB - Choice viewing behavior when looking at affective scenes was assessed to examine differences due to hedonic content and gender by monitoring eye movements in a selective looking paradigm. On each trial, participants viewed a pair of pictures that included a neutral picture together with an affective scene depicting either contamination, mutilation, threat, food, nude males, or nude females. The duration of time that gaze was directed to each picture in the pair was determined from eye fixations. Results indicated that viewing choices varied with both hedonic content and gender. Initially, gaze duration for both men and women was heightened when viewing all affective contents, but was subsequently followed by significant avoidance of scenes depicting contamination or nude males. Gender differences were most pronounced when viewing pictures of nude females, with men continuing to devote longer gaze time to pictures of nude females throughout viewing, whereas women avoided scenes of nude people, whether male or female, later in the viewing interval. For women, reported disgust of sexual activity was also inversely related to gaze duration for nude scenes. Taken together, selective looking as indexed by eye movements reveals differential perceptual intake as a function of specific content, gender, and individual differences. PMID- 26156940 TI - Evaluation of telemedicine centres in Madhya Pradesh, Central India. AB - In a developing country such as India, there is substantial inequality in health care distribution. Telemedicine facilities were established in Madhya Pradesh in 2007-2008. The purpose of this study was to evaluate the infrastructure, equipment, manpower, and functional status of Indian Space and Research Organisation (ISRO) telemedicine nodes in Madhya Pradesh. All district hospitals and medical colleges with nodes were visited by a team of three members. The study was conducted from December 2013-January 2014. The team recorded the structural facility situation and physical conditions on a predesigned pro forma. The team also conducted interviews with the nodal officers, data entry operator and other relevant people at these centres. Of the six specialist nodes, four were functional and two were non-functional. Of 10 patient nodes, two nodes were functional, four were semi-functional and four were non-functional. Most of the centres were not working due to a problem with their satellite modem. The overall condition of ISRO run telemedicine centres in Madhya Pradesh was found to be poor. Most of these centres failed to provide telemedicine consultations. We recommend replacing this system with another cost effective system available in the state wide area network (SWAN). We suggest the concept of the virtual out patient department. PMID- 26156941 TI - Physical exercise at the workplace reduces perceived physical exertion during healthcare work: cluster randomized controlled trial. AB - BACKGROUND: High physical exertion during work is a risk factor for musculoskeletal pain and long-term sickness absence. Physical exertion (RPE) reflects the balance between physical work demands and physical capacity of the individual. Thus, increasing the physical capacity through physical exercise may decrease physical exertion during work. This study investigates the effect of workplace-based versus home-based physical exercise on physical exertion during work (WRPE) among healthcare workers. METHODS: 200 female healthcare workers (age: 42.0, body mass index: 24.1, average pain intensity: 3.1 on a scale of 0 to 10, average WRPE: 3.6 on a scale of 0 to 10) from 18 departments at three participating hospitals. Participants were randomly allocated at the cluster level to 10 weeks of: (1) workplace physical exercise (WORK) performed in groups during working hours for 5*10 minutes per week and up to five group-based coaching sessions on motivation for regular physical exercise, or (2) home-based physical exercise (HOME) performed during leisure time for 5*10 minutes per week. Physical exertion was assessed at baseline and at 10-week follow-up. RESULTS: 2.2 (SD: 1.1) and 1.0 (SD: 1.2) training sessions were performed per week in WORK and HOME, respectively. Physical exertion was reduced more in WORK than HOME (p<0.01). Between-group differences in physical exertion at follow-up (WORK vs. HOME) was -0.5 points (95% CI -0.8 to -0.2). Within-group effect size (Cohen's d) in WORK and HOME was 0.43 and 0.13, respectively. CONCLUSIONS: Physical exercise performed at the workplace appears more effective than home-based exercise in reducing physical exertion during daily work tasks in healthcare workers. PMID- 26156943 TI - WHO is unfit for health emergencies, says independent panel. PMID- 26156942 TI - Clostridium difficile ribotypes in Austria: a multicenter, hospital-based survey. AB - A prospective, noninterventional survey was conducted among Clostridium difficile positive patients identified in the time period of July until October 2012 in 18 hospitals distributed across all nine Austrian provinces. Participating hospitals were asked to send stool samples or isolates from ten successive patients with C.difficile infection to the National Clostridium difficile Reference Laboratory at the Austrian Agency for Health and Food Safety for PCR-ribotyping and in vitro susceptibility testing. A total of 171 eligible patients were identified, including 73 patients with toxin-positive stool specimens and 98 patients from which C. difficile isolates were provided. Of the 159 patients with known age, 127 (74.3%) were 65 years or older, the median age was 76 years (range: 9-97 years), and the male to female ratio 2.2. Among these patients, 73% had health care-associated and 20% community-acquired C. difficile infection (indeterminable 7%). The all-cause, 30-day mortality was 8.8% (15/171). Stool samples yielded 46 different PCR-ribotypes, of which ribotypes 027 (20%), 014 (15.8%), 053 (10.5%), 078 (5.3%), and 002 (4.7%) were the five most prevalent. Ribotype 027 was found only in the provinces Vienna, Burgenland, and Lower Austria. Severe outcome of C. difficile infection was found to be associated with ribotype 053 (prevalence ratio: 3.04; 95% CI: 1.24, 7.44), not with the so-called hypervirulent ribotypes 027 and 078. All 027 and 053 isolates exhibited in vitro resistance against moxifloxacin. Fluoroquinolone use in the health care setting must be considered as a factor favoring the spread of these fluoroquinolone resistant C. difficile clones. PMID- 26156944 TI - Results of surgical treatment for secondary spontaneous pneumothorax according to underlying diseases. AB - OBJECTIVES: The outcome of surgical treatment for secondary spontaneous pneumothorax (SSP) has rarely been investigated. METHODS: We retrospectively reviewed 183 patients who underwent surgery for SSP. We categorized the patients into three groups according to underlying diseases: Group A (chronic obstructive pulmonary disease), Group B (interstitial pneumonia [IP]) and Group C (others). We defined treatment success as surgery without hospital mortality, postoperative complications, death within 6 months or ipsilateral recurrence of pneumothorax within 2 years. We assessed the risk factors for unsuccessful treatment using a Cox regression hazard model. RESULTS: There were 123 patients in Group A, 20 in Group B and 40 in Group C. The hospital mortality rates were 2, 15 and 0% in Groups A, B and C, respectively. The hospital mortality, morbidity and pneumothorax recurrence rates in the IP group were higher than in the other groups. The 5-year overall survival rates were 78, 32 and 84% in Groups A, B and C, respectively; the prognosis of the IP group was significantly poorer. The treatment success rates were 86, 45 and 83% in Groups A, B and C, respectively. SSPs caused by IP and SSPs requiring open surgery were identified as the risk factors for unsuccessful treatment. CONCLUSIONS: Surgery for SSP caused by underlying diseases other than IP yielded favourable results. However, a careful examination of surgical indication and a realistic disclosure for informed consent are required for patients with SSP caused by IP, because of the high treatment failure rate. PMID- 26156945 TI - Geometric ring annuloplasty as an adjunct to aortic valve repair: clinical investigation of the HAART 300 device. AB - OBJECTIVES: This study assessed the safety and efficacy of an internal geometric annuloplasty ring in a regulatory trial of aortic valve reconstruction (ClinicalTrials.gov Identifier: NCT01400841). METHODS: Sixty-five patients with predominant moderate-to-severe trileaflet aortic insufficiency (AI) underwent aortic valve repair with an average age of 63 +/- 13 years (mean +/- SD). All had initial implantation of an internal aortic annuloplasty ring to correct annular dilatation and facilitate leaflet reconstruction. Leaflet plication was performed for prolapse in 80% of patients, and more complex leaflet procedures, usually employing autologous pericardium, were required in 22%. Ascending aortic and/or root aneurysms were replaced in 62%. RESULTS: Follow-up was for a maximum of 3 years and a mean of 2 years. No in-hospital operative mortalities, major complications or early or late valve-related events occurred. The annular diameter before repair was 26.5 +/- 2.3 mm, and the average ring diameter used was 21.5 +/- 1.6 mm. The preoperative AI grade (0-4) was 2.9 +/- 0.8 and improved after repair to 0.6 +/- 0.7 (P < 0.0001), as did the NYHA class. The mean valve gradient was 8.6 +/- 4.3 mmHg, and at 3 years, the Kaplan-Meier survival rate was 95%, with no valve-related mortality. Over the 3 years, aortic valve replacement was required in 7 patients (10.8%) for reasons usually related to surgical technique. Most repair failures occurred early, and results stabilized after 6 months. No structural complications of the rings were observed. CONCLUSIONS: Geometric ring annuloplasty was a safe and effective adjunct to aortic valve repair. Initial correction of annular dilatation seemed to facilitate overall reconstruction. Because most early repair failures were technical, increasing experience with geometric ring annuloplasty for aortic valve reconstruction has the potential to standardize and improve outcomes. PMID- 26156946 TI - A 62-year-old Man with Facial and Finger Twitching. PMID- 26156947 TI - A 76 Year-Old Woman with Sleep and Waking Stridor, Sleep Talking, Orthostatic Hypotension, and Imbalance. PMID- 26156948 TI - Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases. AB - STUDY OBJECTIVES: The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. METHODS AND RESULTS: Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. CONCLUSIONS: Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. PMID- 26156949 TI - Long-Term Follow-up Investigation of Isolated Rapid Eye Movement Sleep Without Atonia Without Rapid Eye Movement Sleep Behavior Disorder: A Pilot Study. AB - STUDY OBJECTIVES: Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a harbinger of synuclein-mediated neurodegenerative diseases. It is unknown if this also applies to isolated REM sleep without atonia (RWA). We performed a long-term follow-up investigation of subjects with isolated RWA. METHODS: Participants were recruited from 50 subjects with isolated RWA who were identified at the sleep laboratory of the Department of Neurology at the Medical University of Innsbruck between 2003 and 2005. Eligible subjects underwent follow up clinical examination, polysomnography, and assessment of neurodegenerative biomarkers (cognitive impairment, finger speed deficit, impaired color vision, olfactory dysfunction, orthostatic hypotension, and substantia nigra hyperechogenicity). RESULTS: After a mean of 8.6 +/- 0.9 y, 1 of 14 participating subjects (7.3%) progressed to RBD. Ten of 14 RWA subjects (71.4%) were positive for at least one neurodegenerative biomarker. Substantia nigra hyperechogenicity and presence of mild cognitive impairment were both present in 4 of 14 subjects with isolated RWA. Electromyographic activity measures increased significantly from baseline to follow-up polysomnography ("any" mentalis and both anterior tibialis muscles: 32.5 +/- 9.4 versus 52.2 +/- 16.6%; p = 0.004). CONCLUSION: This study provides first evidence that isolated RWA is an early biomarker of synuclein-mediated neurodegeneration. These results will have to be replicated in larger studies with longer observational periods. If confirmed, these disease findings have implications for defining at-risk cohorts for Parkinson disease. PMID- 26156950 TI - Fiber and Saturated Fat Are Associated with Sleep Arousals and Slow Wave Sleep. AB - STUDY OBJECTIVES: Sleep restriction alters food intake, but less is known about how dietary patterns affect sleep. Current goals were to determine whether: (1) sleep is different after consumption of a controlled diet vs. an ad libitum diet, and (2) dietary intake during ad libitum feeding is related to nocturnal sleep. METHODS: Twenty-six normal weight adults (30-45 y), habitually sleeping 7-9 h/night, participated in a randomized-crossover inpatient study with 2 phases of 5 nights: short (4 h in bed) or habitual (9 h in bed) sleep. Only data from the habitual sleep phase were used for the present analyses. During the first 4 days, participants consumed a controlled diet; on day 5, food intake was self-selected. Linear regression was used to determine relations between daytime food intake and nighttime sleep on day 5. RESULTS: Sleep duration did not differ after 3 days of controlled feeding vs. a day of ad libitum intake. However, sleep after ad libitum eating had less slow wave sleep (SWS, P = 0.0430) and longer onset latency (P = 0.0085). Greater fiber intake predicted less stage 1 (P = 0.0198) and more SWS (P = 0.0286). Percent of energy from saturated fat predicted less SWS (P = 0.0422). Higher percent of energy from sugar and other carbohydrates not considered sugar or fiber was associated with arousals (P = 0.0320 and 0.0481, respectively). CONCLUSIONS: Low fiber and high saturated fat and sugar intake is associated with lighter, less restorative sleep with more arousals. Diet could be useful in the management of sleep disorders but this needs to be tested. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov, #NCT00935402. PMID- 26156951 TI - Predictors of Obstructive Sleep Apnea on Polysomnography after a Technically Inadequate or Normal Home Sleep Test. AB - STUDY OBJECTIVES: Home sleep testing (HST) is an accepted alternative to polysomnography (PSG) for diagnosing obstructive sleep apnea (OSA) in high-risk populations. Clinical guidelines recommend PSG in cases where the HST is technically inadequate (TI) or fails to establish the diagnosis of OSA in patients with high pretest probability. This retrospective study evaluated predictors of OSA on PSG within patients who had a TI or normal HST. METHODS: Electronic medical records were reviewed on 1,157 patients referred for HST at our sleep center. Two hundred thirty-eight patients had a TI or normal HST with subsequent PSG. Age, BMI, Epworth score, HST result, and PSG-based apnea-hypopnea index (AHI) were abstracted. RESULTS: Two hundred thirty-eight consecutive patients with either a normal HST (n = 127) or TI HST (n = 111) underwent subsequent PSG. Of 127 who had a normal HST, 76% had a normal PSG and 24% had OSA (23 mild, 6 moderate, 1 severe). Of 111 who had a TI HST, 29% had a normal PSG and 71% had OSA (43 mild, 19 moderate, 17 severe). Individuals younger than 50 years old with a normal HST were more likely to have a normal PSG. Older age predicted diagnosis of OSA on PSG among individuals with a TI HST. CONCLUSION: In this retrospective analysis of a clinical sample, when the HST is interpreted as normal in a younger patient population, the subsequent PSG is likewise normal in majority of the patients, although significant OSA is sometimes discovered. When a HST is read as TI, the majority of patients have OSA. PMID- 26156952 TI - A 5-Year Follow-up Study on the Relationship between Obstructive Sleep Apnea and Parkinson Disease. AB - STUDY OBJECTIVE: Sleep disturbances are among the most common nonmotor symptoms of Parkinson disease. However, no large epidemiological data regarding the association between obstructive sleep apnea (OSA) and Parkinson disease have been reported. The goal of this study was to investigate the risk for Parkinson disease during a 5-y follow-up period after a diagnosis of OSA using a population based dataset. METHODS: The data for this retrospective longitudinal cohort study were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We identified 1,532 patients with OSA as the study cohort and randomly selected 7,660 patients as the comparison cohort. Each subject was individually followed up for a 5-y period to identify those in whom Parkinson disease subsequently developed. Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-y risk of subsequent Parkinson disease between the study cohort and comparison cohort. RESULTS: Of the 9,192 total patients, Parkinson disease developed in 0.73% during the 5-y follow-up period: 1.24% and 0.63% in the OSA and control cohorts, respectively. After censoring patients who died during the follow-up period and adjusting for socio-demographic characteristics, the hazard ratio (HR) of Parkinson disease during the 5-y follow-up period for patients with OSA was 2.26 (95% confidence interval [CI] = 1.32-3.88) compared with comparison patients. In addition, among females, the adjusted HR of Parkinson disease was 3.54 (95% CI = 1.50-8.34) for patients with OSA compared to patients without OSA. However, among males, there was no significantly increased hazard of Parkinson disease for patients with OSA compared to those without OSA. CONCLUSIONS: Female patients with OSA were found to be at a significant risk of subsequent Parkinson disease during a 5-y follow-up period. PMID- 26156953 TI - A Young Man Running Out of Treatment Options. PMID- 26156954 TI - A Comparative Analysis of Sleep Disordered Breathing in Active Duty Service Members with and without Combat-Related Posttraumatic Stress Disorder. AB - STUDY OBJECTIVES: Posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are frequently co-occurring illnesses. The purpose of this study was to determine whether comorbid PTSD/OSA is associated with increased PTSD symptoms or decreased OSA severity compared to PTSD or OSA alone in recently deployed Active Duty Service Members (ADSM). METHODS: Cross-sectional observational study of ADSM who returned from combat within 24 months. Participants underwent an attended diagnostic polysomnogram and were assessed for PTSD, depression, combat exposure severity, sleepiness, and sleep quality with validated clinical instruments. RESULTS: Our study included 109 military personnel who returned from a combat deployment within 24 months with a mean age of 34.3 +/- 8.23 and BMI of 30.8 +/- 3.99. Twenty-four participants had PTSD/OSA, 68 had OSA, and 17 had PTSD. Mean PTSD Checklist- Military Version (PCL-M) scores were 62.0 +/- 8.95, 60.5 +/- 4.73, and 32.5 +/- 8.95 in PTSD/OSA, PTSD, and OSA, respectively. The mean AHI was 16.9 +/- 15.0, 18.9 +/- 17.0, and 1.73 +/- 1.3 for those with PTSD/OSA, OSA, and PTSD. PTSD symptoms and OSA severity in military personnel with comorbid PTSD/OSA were not significantly different from those with PTSD or OSA alone. On multivariate analysis, BMI was a significant predictor of OSA (OR, 1.21; 95% CI, 1.04-1.44) and age trended towards significance. Depression, but not OSA severity, was associated with PTSD symptoms. CONCLUSIONS: Following recent combat exposure, comorbid PTSD/OSA is not associated with increased PTSD symptoms or decreased severity of OSA. Early evaluation after traumatic exposure for comorbid OSA is indicated in PTSD patients with sleep complaints given the high co-occurrence and adverse clinical implications. PMID- 26156955 TI - Obstructive Sleep Apnea is Not Associated with an Increased Risk of Osteoporosis: a Systematic Review and Meta-Analysis. PMID- 26156956 TI - Is Metabolic Syndrome Associated with Obstructive Sleep Apnea in Obese Adolescents? AB - OBJECTIVE: To investigate whether there is an association between metabolic syndrome and obstructive sleep apnea syndrome (OSAS) in obese adolescents. METHODS: In total, 240 pubertal children or prepubertal children older than 11 y recruited consecutively from the pediatric endocrinology unit, obesity clinic. Patients with tonsillar and adenoid hypertrophy (grade 3/4), systemic illnesses, or chronic drug usage were excluded. After anthropometric measurement and laboratory study, patients were divided into two groups according to metabolic syndrome (MS): MS and non-MS. Overnight polysomnographic evaluation was performed and 104 subjects were included for statistical analysis. The two groups were compared in terms of sleep efficiency, number of awakenings per night, oxygen desaturation index, snoring time, and obstructive/central/ mixed apnea-hypopnea index (AHI). RESULTS: Of the obese adolescents, 51 had MS and 53 did not. The AHI was >= 1 in 25 of the 53 non-MS children (47.2%) and in 25 of the 51 MS children (49%). The median obstructive AHI value was 0.9 (0.2-2.4) and total AHI was 0.9 (0.2-2.5) in the MS group; these values were 0.9 (0.25-3.55) and 0.9 (0.3-3.55), respectively, in the non-MS group. Obstructive, central, mixed, and total AHI values in the MS and non-MS groups were not statistically significantly different (p > 0.05). CONCLUSIONS: In our study, we did not find an association between MS and sleep apnea in obese adolescents. PMID- 26156957 TI - The Association of Restless Legs Syndrome to History of Gestational Diabetes in an Appalachian Primary Care Population. AB - OBJECTIVES: Restless legs syndrome (RLS) is a burdensome sensorimotor disorder that has been linked to diabetes and obesity. However, the relationship of RLS to gestational diabetes mellitus (GDM), a common pregnancy complication strongly associated with obesity and a harbinger of diabetes, remains unknown. In this study, we examined the association of RLS to history of GDM in a sample of older female primary care patients. METHODS: Participants were community-dwelling women aged >= 40 years drawn from an anonymous survey study of West Virginia adult primary care patients. Data gathered included detailed information on demographics, lifestyle factors, reproductive history, sleep patterns, and medical history; the survey also included an RLS diagnostic questionnaire. Women who were pregnant or had missing data on key variables were excluded from the analyses. RESULTS: Of the 498 participants included in the final analytic sample, 24.5% met diagnostic criteria for RLS (17.9% with symptoms at least once/week). After adjustment for demographics, lifestyle characteristics, body mass index, diabetes and other comorbid conditions, parity, and other factors, those reporting history of GDM were almost three times as likely to meet criteria for RLS (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.3, 5.3). This association increased in magnitude with increasing symptom frequency (adjusted OR for RLS symptoms >= 3*/week = 4.8, CI 2.1, 11.2, p for trend = 0.004). CONCLUSIONS: History of GDM was strongly and positively related to RLS in this study of older female primary care patients, offering further support for a possible role of metabolic dysregulation in RLS development. PMID- 26156958 TI - Consumer Sleep Technologies: A Review of the Landscape. AB - OBJECTIVE: To review sleep related consumer technologies, including mobile electronic device "apps," wearable devices, and other technologies. Validation and methodological transparency, the effect on clinical sleep medicine, and various social, legal, and ethical issues are discussed. METHODS: We reviewed publications from the digital libraries of the Association for Computing Machinery, Institute of Electrical and Electronics Engineers, and PubMed; publications from consumer technology websites; and mobile device app marketplaces. Search terms included "sleep technology," "sleep app," and "sleep monitoring." RESULTS: Consumer sleep technologies are categorized by delivery platform including mobile device apps (integrated with a mobile operating system and utilizing mobile device functions such as the camera or microphone), wearable devices (on the body or attached to clothing), embedded devices (integrated into furniture or other fixtures in the native sleep environment), accessory appliances, and conventional desktop/website resources. Their primary goals include facilitation of sleep induction or wakening, self-guided sleep assessment, entertainment, social connection, information sharing, and sleep education. CONCLUSIONS: Consumer sleep technologies are changing the landscape of sleep health and clinical sleep medicine. These technologies have the potential to both improve and impair collective and individual sleep health depending on method of implementation. PMID- 26156959 TI - New Wnt/beta-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals. AB - OBJECTIVES: We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The signature included the canonical Wnt target gene BAMBI, which promoted experimental metastasis in mice. Here, we identified three new direct Wnt target genes from the signature, and studied their functions in epithelial-mesenchymal transition (EMT), cell migration and experimental metastasis. DESIGN: We examined experimental liver metastases following injection of selected tumour cells into spleens of NOD/SCID mice. Molecular and cellular techniques were used to identify direct transcription target genes of Wnt/beta-catenin signals. Microarray analyses and experiments that interfered with cell migration through inhibitors were performed to characterise downstream signalling systems. RESULTS: Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of beta-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways. CONCLUSIONS: We identified new direct Wnt/beta-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis. PMID- 26156960 TI - Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy. AB - OBJECTIVE: Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. DESIGN: In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. RESULTS: In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. CONCLUSIONS: Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. PMID- 26156961 TI - A Randomized Control Trial of Working Memory Training With and Without Strategy Instruction: Effects on Young Children's Working Memory and Comprehension. AB - Researchers are increasingly interested in working memory (WM) training. However, it is unclear whether it strengthens comprehension in young children who are at risk for learning difficulties. We conducted a modest study of whether the training of verbal WM would improve verbal WM and passage listening comprehension and whether training effects differed between two approaches: training with and without strategy instruction. A total of 58 first-grade children were randomly assigned to three groups: WM training with a rehearsal strategy, WM training without strategy instruction, and controls. Each member of the two training groups received a one-to-one, 35-min session of verbal WM training on each of 10 consecutive school days, totaling 5.8 hr. Both training groups improved on trained verbal WM tasks, with the rehearsal group making greater gains. Without correction for multiple group comparisons, the rehearsal group made reliable improvements over controls on an untrained verbal WM task and on passage listening comprehension and listening retell measures. The no-strategy instruction group outperformed controls on passage listening comprehension. When corrected for multiple contrasts, these group differences disappeared but were associated with moderate to large effect sizes. Findings suggest-however tentatively-that brief but intensive verbal WM training may strengthen the verbal WM and comprehension performance of young children at risk. Necessary caveats and possible implications for theory and future research are discussed. PMID- 26156962 TI - A marginalized two-part model for longitudinal semicontinuous data. AB - In health services research, it is common to encounter semicontinuous data, characterized by a point mass at zero followed by a right-skewed continuous distribution with positive support. Examples include health expenditures, in which the zeros represent a subpopulation of patients who do not use health services, while the continuous distribution describes the level of expenditures among health services users. Longitudinal semicontinuous data are typically analyzed using two-part random-effect mixtures with one component that models the probability of health services use, and a second component that models the distribution of log-scale positive expenditures among users. However, because the second part conditions on a non-zero response, obtaining interpretable effects of covariates on the combined population of health services users and non-users is not straightforward, even though this is often of greatest interest to investigators. Here, we propose a marginalized two-part model for longitudinal data that allows investigators to obtain the effect of covariates on the overall population mean. The model additionally provides estimates of the overall population mean on the original, untransformed scale, and many covariates take a dual population average and subject-specific interpretation. Using a Bayesian estimation approach, this model maintains the flexibility to include complex random-effect structures and easily estimate functions of the overall mean. We illustrate this approach by evaluating the effect of a copayment increase on health care expenditures in the Veterans Affairs health care system over a four year period. PMID- 26156963 TI - "Beyond aid" investments in private healthcare in developing countries. PMID- 26156966 TI - Surgical outcomes and prognostic factors of emergency surgery for colonic perforation: would fecal contamination increase morbidity and mortality? AB - PURPOSE: Complications resulting from colonic perforation are related to secondary peritonitis due to bacterial or fecal contamination. We investigated outcomes of emergency surgery for colonic perforation associated with fecal contamination with regard to early and late postoperative complication rates and mortality rates, and investigated prognostic factors influencing those outcomes. METHODS: A retrospective analysis of prospectively collected data on factors influencing complications and mortality rates was conducted on data from 152 patients who had undergone emergent operations for colonic perforation between January 2005 and December 2011. Patients were categorized into two groups: those with and without gross fecal contamination at the time of operation. RESULTS: Forty-one (26.9 %) patients had gross fecal contamination. Patients who had fetal contamination had a higher Mannheim peritonitis index (31.3 +/- 5.1 vs. 21.9 +/- 7.2, p < 0.001), higher organ failure rate (53.7 vs. 24.3 %, p = 0.001), and longer operating time (168.8 +/- 49.9 vs. 144.8 +/- 66.1 min, p = 0.036) than patients without fecal contamination. Early complications (<30 days) occurred more frequently in the fecal contamination group (82.9 vs. 49.5 %, p = 0.001), although late complications (46.2 vs. 39.3 %, p = 0.942) and mortality (17.1 vs. 8.1 %, p = 0.110) did not differ. In multivariate analysis, fecal contamination significantly predicted early complications (odds ratio, 2.78; p = 0.037) but not late complications or mortality. CONCLUSIONS: The frequency of early complications can increase if fecal contamination exists. However, when early complications are well managed, fecal contamination does not significantly influence occurrences late complications or mortality. PMID- 26156967 TI - Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise. AB - During submaximal exercise fatty acids are a predominant energy source for muscle contractions. An important regulator of fatty acid oxidation is acetyl-CoA carboxylase (ACC), which exists as two isoforms (ACC1 and ACC2) with ACC2 predominating in skeletal muscle. Both ACC isoforms regulate malonyl-CoA production, an allosteric inhibitor of carnitine palmitoyltransferase 1 (CPT-1); the primary enzyme controlling fatty acyl-CoA flux into mitochondria for oxidation. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is activated during exercise or by pharmacological agents such as metformin and AICAR. In resting muscle the activation of AMPK with AICAR leads to increased phosphorylation of ACC (S79 on ACC1 and S221 on ACC2), which reduces ACC activity and malonyl-CoA; effects associated with increased fatty acid oxidation. However, whether this pathway is vital for regulating skeletal muscle fatty acid oxidation during conditions of increased metabolic flux such as exercise/muscle contractions remains unknown. To examine this we characterized mice lacking AMPK phosphorylation sites on ACC2 (S212 in mice/S221 in humans-ACC2 knock-in [ACC2-KI]) or both ACC1 (S79) and ACC2 (S212) (ACC double knock-in [ACCD KI]) during submaximal treadmill exercise and/or ex vivo muscle contractions. We find that surprisingly, ACC2-KI mice had normal exercise capacity and whole-body fatty acid oxidation during treadmill running despite elevated muscle ACC2 activity and malonyl-CoA. Similar results were observed in ACCD-KI mice. Fatty acid oxidation was also maintained in muscles from ACC2-KI mice contracted ex vivo. These findings indicate that pathways independent of ACC phosphorylation are important for regulating skeletal muscle fatty acid oxidation during exercise/muscle contractions. PMID- 26156968 TI - Effects of 4-aminopyridine on action potentials generation in mouse sinoauricular node strips. AB - The physiological role of Ito has yet to be clarified. The goal of this study is to investigate the possible contribution of the transient outward current (Ito) on the generation of transmembrane action potentials (APs) and the sensitivity of mouse sinoauricular node (SAN) cells to a 4-aminopyridine (4AP) as Ito blocker. The electrophysiological identification of cells was performed in the sinoauricular node artery area (nstrips = 38) of the subendocardial surface using microelectrode technique. In this study, for the first time, it was observed that dependence duration of action potential at the level of 20% repolarization (APD20) level under a 4AP concentration in the pacemaker SAN and auricular cells corresponds to a curve predicted by Hill's equation. APD20 raised by 70% and spike duration of AP increased by 15-25%, when 4AP concentration was increased from 0.1 to 5.0 mmol/L. Auricular cells were found to be more sensitive to 4AP than true pacemaker cells. This was accompanied by a decrease in the upstroke velocity as compared to the control. Our data and previous findings in the literature lead us to hypothesize that the 4AP-sensitive current participates in the repolarization formation of pacemaker and auricular type cells. Thus, study concerning the inhibitory effects of lidocaine and TTX on APD20 can explain the phenomenon of the decrease in upstroke velocity, which, for the first time, was observed after exposure to 4AP. Duration of AP at the level of 20% repolarization (APD20) under a 4-AP concentration 0.5 mmol/L in the true pacemaker cells lengthen by 60-70% with a control. PMID- 26156971 TI - Analyzing Determinants of Hospitals' Accountable Care Organizations Participation: A Resource Dependency Theory Perspective. AB - Accountable care organizations (ACOs) are rapidly being implemented across the United States, but little is known about what environmental and organizational factors are associated with hospital participation in ACOs. Using resource dependency theory, this study examines external environmental characteristics and organizational characteristics that relate to hospital participation in Medicare ACOs. Results indicate hospitals operating in more munificent environments (as measured by income per capita: beta = 0.00002, p < .05) and more competitive environments (as measured by Health Maintenance Organization penetration: beta = 1.86, p < .01) are more likely to participate in ACOs. Organizational characteristics including hospital ownership, health care system membership, electronic health records implementation, hospital type, percentage of Medicaid inpatient discharge, and number of nursing home beds per 1,000 population over 65 are also related to ACO participation. Should the anticipated benefits of ACOs be realized, findings from this study can guide strategies to encourage hospitals that have not gotten involved in ACOs. PMID- 26156972 TI - Amoebic liver abscess: a report from central India. AB - Amoebic liver abscess is a serious but curable hepatic illness predominantly seen in tropical countries. We describe our experience of clinical presentation, laboratory parameters, radiological findings and treatment strategies. This is a retrospective analysis of 114 patients who were admitted from January 2012 to September 2014 at our centre. The mean age of presentation was 41.7 +/- 13.9 years, the majority of patients were male (86.8%) with chronic alcoholism (63.2%). Most of the patients had a solitary right lobe liver abscess. Abdominal pain, fever, tachycardia and hepatomegaly were the most common clinical findings while hypoalbuminaemia, anaemia, leucocytosis and electrolyte imbalance were the most common laboratory abnormalities. A significant number of patients could be managed with antibiotics only (45.6%), percutaneous radiological drainage techniques being an important adjunct in selected cases (percutaneous needle aspiration, 20.2%; percutaneous pigtail catheter drainage, 30.7%). Surgical intervention was required in only a few cases (3.5%). Mortality was 3.5%. PMID- 26156970 TI - Cushing's syndrome: update on signs, symptoms and biochemical screening. AB - Endogenous pathologic hypercortisolism, or Cushing's syndrome, is associated with poor quality of life, morbidity, and increased mortality. Early diagnosis may mitigate against this natural history of the disorder. The clinical presentation of Cushing's syndrome varies, in part related to the extent and duration of cortisol excess. When hypercortisolism is severe, its signs and symptoms are unmistakable. However, most of the signs and symptoms of Cushing's syndrome are common in the general population (e.g., hypertension and weight gain) and not all are present in every patient. In addition to classical features of glucocorticoid excess, such as proximal muscle weakness and wide purple striae, patients may present with the associated comorbidities that are caused by hypercortisolism. These include cardiovascular disease, thromboembolic disease, psychiatric and cognitive deficits, and infections. As a result, internists and generalists must consider Cushing's syndrome as a cause, and endocrinologists should search for and treat these comorbidities. Recommended tests to screen for Cushing's syndrome include 1 mg dexamethasone suppression, urine free cortisol, and late night salivary cortisol. These may be slightly elevated in patients with physiologic hypercortisolism, which should be excluded, along with exogenous glucocorticoid use. Each screening test has caveats and the choice of tests should be individualized based on each patient's characteristics and lifestyle. The objective of this review is to update the readership on the clinical and biochemical features of Cushing's syndrome that are useful when evaluating patients for this diagnosis. PMID- 26156969 TI - Unique gene program of rat small resistance mesenteric arteries as revealed by deep RNA sequencing. AB - Deep sequencing of RNA samples from rat small mesenteric arteries (MA) and aorta (AO) identified common and unique features of their gene programs. ~5% of mRNAs were quantitatively differentially expressed in MA versus AO. Unique transcriptional control in MA smooth muscle is suggested by the selective or enriched expression of transcription factors Nkx2-3, HAND2, and Tcf21 (Capsulin). Enrichment in AO of PPAR transcription factors and their target genes of mitochondrial function, lipid metabolism, and oxidative phosphorylation is consistent with slow (oxidative) tonic smooth muscle. In contrast MA was enriched in contractile and calcium channel mRNAs suggestive of components of fast (glycolytic) phasic smooth muscle. Myosin phosphatase regulatory subunit paralogs Mypt1 and p85 were expressed at similar levels, while smooth muscle MLCK was the only such kinase expressed, suggesting functional redundancy of the former but not the latter in accordance with mouse knockout studies. With regard to vaso regulatory signals, purinergic receptors P2rx1 and P2rx5 were reciprocally expressed in MA versus AO, while the olfactory receptor Olr59 was enriched in MA. Alox15, which generates the EDHF HPETE, was enriched in MA while eNOS was equally expressed, consistent with the greater role of EDHF in the smaller arteries. mRNAs that were not expressed at a level consistent with impugned function include skeletal myogenic factors, IKK2, nonmuscle myosin, and Gnb3. This screening analysis of gene expression in the small mesenteric resistance arteries suggests testable hypotheses regarding unique aspects of small artery function in the regional control of blood flow. PMID- 26156973 TI - Where can colorectal cancer screening interventions have the most impact? AB - BACKGROUND: Although colorectal cancer death rates in the United States have declined by half since 1970, large geographic disparities persist. Spatial identification of high-risk areas can facilitate targeted screening interventions to close this gap. METHODS: We used the Getis-Ord Gi* statistic within ArcGIS to identify contemporary colorectal cancer "hotspots" (spatial clusters of counties with high rates) based on county-level mortality data from the national vital statistics system. Hotspots were compared with the remaining aggregated counties (non-hotspot United States) by plotting trends from 1970 to 2011 and calculating rate ratios (RR). Trends were quantified using joinpoint regression. RESULTS: Spatial mapping identified three distinct hotspots in the contemporary United States where colorectal cancer death rates were elevated. The highest rates were in the largest hotspot, which encompassed 94 counties in the Lower Mississippi Delta [Arkansas (17), Illinois (16), Kentucky (3), Louisiana (6), Mississippi (27), Missouri (15), and Tennessee (10)]. During 2009 to 2011, rates here were 40% higher than the non-hotspot United States [RR, 1.40; 95% confidence interval (CI), 1.34-1.46], despite being 18% lower during 1970 to 1972 (RR, 0.82; 95% CI, 0.78-0.86). The elevated risk was similar in blacks and whites. Notably, rates among black men in the Delta increased steadily by 3.5% per year from 1970 to 1990, and have since remained unchanged. Rates in hotspots in west central Appalachia and eastern Virginia/North Carolina were 18% and 9% higher, respectively, than the non-hotspot United States during 2009 to 2011. CONCLUSIONS: Advanced spatial analysis revealed large pockets of the United States with excessive colorectal cancer death rates. IMPACT: These well-defined areas warrant prioritized screening intervention. PMID- 26156974 TI - Update on Benign Transient Hyperphosphatasemia: Recognizing an Underappreciated Condition. PMID- 26156975 TI - Bilious Emesis and Small Bowel Obstruction in a Young Male. PMID- 26156976 TI - Assessment of a Smartphone Otoscope Device for the Diagnosis and Management of Otitis Media. PMID- 26156977 TI - Vision Diagnoses Are Common After Concussion in Adolescents. AB - OBJECTIVE: To determine the prevalence of vision diagnoses after concussion in adolescents. METHODS: Cross-sectional study from July 1, 2013 to February 28, 2014, of patients aged 11 to 17 years with concussion evaluated in a comprehensive concussion program. RESULTS: A total of 100 adolescents were examined, with a mean age of 14.5 years. Overall, 69% had one or more of the following vision diagnoses: accommodative disorders (51%), convergence insufficiency (49%), and saccadic dysfunction (29%). In all, 46% of patients had more than one vision diagnosis. CONCLUSIONS: A high prevalence of vision diagnoses (accommodative, binocular convergence, and saccadic eye movement disorders) was found in this sample of adolescents with concussion, with some manifesting more than one vision diagnosis. These data indicate that a comprehensive visual examination may be helpful in the evaluation of a subset of adolescents with concussion. Academic accommodations for students with concussion returning to the classroom setting should account for these vision diagnoses. PMID- 26156978 TI - Prevalence of Undiagnosed Structural Heart Disease in Children Undergoing Echocardiography for Kawasaki Disease. PMID- 26156979 TI - Cleaning Earwax Impaction: Clinical Tips for the Primary Care Clinician. PMID- 26156980 TI - The Antibiogram Project: Using the Hospital Antibiogram to Introduce Antimicrobial Stewardship to Pediatric Medical Residents. PMID- 26156981 TI - Is There a General Role for the Monkey Oculomotor System in Perceptual Decision Making? PMID- 26156982 TI - Visual Learning Induces Changes in Resting-State fMRI Multivariate Pattern of Information. AB - When measured with functional magnetic resonance imaging (fMRI) in the resting state (R-fMRI), spontaneous activity is correlated between brain regions that are anatomically and functionally related. Learning and/or task performance can induce modulation of the resting synchronization between brain regions. Moreover, at the neuronal level spontaneous brain activity can replay patterns evoked by a previously presented stimulus. Here we test whether visual learning/task performance can induce a change in the patterns of coded information in R-fMRI signals consistent with a role of spontaneous activity in representing task relevant information. Human subjects underwent R-fMRI before and after perceptual learning on a novel visual shape orientation discrimination task. Task-evoked fMRI patterns to trained versus novel stimuli were recorded after learning was completed, and before the second R-fMRI session. Using multivariate pattern analysis on task-evoked signals, we found patterns in several cortical regions, as follows: visual cortex, V3/V3A/V7; within the default mode network, precuneus, and inferior parietal lobule; and, within the dorsal attention network, intraparietal sulcus, which discriminated between trained and novel visual stimuli. The accuracy of classification was strongly correlated with behavioral performance. Next, we measured multivariate patterns in R-fMRI signals before and after learning. The frequency and similarity of resting states representing the task/visual stimuli states increased post-learning in the same cortical regions recruited by the task. These findings support a representational role of spontaneous brain activity. PMID- 26156983 TI - Selective Gating of Neuronal Activity by Intrinsic Properties in Distinct Motor Rhythms. AB - Many neural circuits show fast reconfiguration following altered sensory or modulatory inputs to generate stereotyped outputs. In the motor circuit of Xenopus tadpoles, I study how certain voltage-dependent ionic currents affect firing thresholds and contribute to circuit reconfiguration to generate two distinct motor patterns, swimming and struggling. Firing thresholds of excitatory interneurons [i.e., descending interneurons (dINs)] in the swimming central pattern generator are raised by depolarization due to the inactivation of Na(+) currents. In contrast, the thresholds of other types of neurons active in swimming or struggling are raised by hyperpolarization from the activation of fast transient K(+) currents. The firing thresholds are then compared with the excitatory synaptic drives, which are revealed by blocking action potentials intracellularly using QX314 during swimming and struggling. During swimming, transient K(+) currents lower neuronal excitability and gate out neurons with weak excitation, whereas their inactivation by strong excitation in other neurons increases excitability and enables fast synaptic potentials to drive reliable firing. During struggling, continuous sensory inputs lead to high levels of network excitation. This allows the inactivation of Na(+) currents and suppression of dIN activity while inactivating transient K(+) currents, recruiting neurons that are not active in swimming. Therefore, differential expression of these currents between neuron types can explain why synaptic strength does not predict firing reliability/intensity during swimming and struggling. These data show that intrinsic properties can override fast synaptic potentials, mediate circuit reconfiguration, and contribute to motor-pattern switching. PMID- 26156984 TI - Dopaminergic Modulation of Decision Making and Subjective Well-Being. AB - The neuromodulator dopamine has a well established role in reporting appetitive prediction errors that are widely considered in terms of learning. However, across a wide variety of contexts, both phasic and tonic aspects of dopamine are likely to exert more immediate effects that have been less well characterized. Of particular interest is dopamine's influence on economic risk taking and on subjective well-being, a quantity known to be substantially affected by prediction errors resulting from the outcomes of risky choices. By boosting dopamine levels using levodopa (l-DOPA) as human subjects made economic decisions and repeatedly reported their momentary happiness, we show here an effect on both choices and happiness. Boosting dopamine levels increased the number of risky options chosen in trials involving potential gains but not trials involving potential losses. This effect could be better captured as increased Pavlovian approach in an approach-avoidance decision model than as a change in risk preferences within an established prospect theory model. Boosting dopamine also increased happiness resulting from some rewards. Our findings thus identify specific novel influences of dopamine on decision making and emotion that are distinct from its established role in learning. PMID- 26156985 TI - fMRI Analysis-by-Synthesis Reveals a Dorsal Hierarchy That Extracts Surface Slant. AB - The brain's skill in estimating the 3-D orientation of viewed surfaces supports a range of behaviors, from placing an object on a nearby table, to planning the best route when hill walking. This ability relies on integrating depth signals across extensive regions of space that exceed the receptive fields of early sensory neurons. Although hierarchical selection and pooling is central to understanding of the ventral visual pathway, the successive operations in the dorsal stream are poorly understood. Here we use computational modeling of human fMRI signals to probe the computations that extract 3-D surface orientation from binocular disparity. To understand how representations evolve across the hierarchy, we developed an inference approach using a series of generative models to explain the empirical fMRI data in different cortical areas. Specifically, we simulated the responses of candidate visual processing algorithms and tested how well they explained fMRI responses. Thereby we demonstrate a hierarchical refinement of visual representations moving from the representation of edges and figure-ground segmentation (V1, V2) to spatially extensive disparity gradients in V3A. We show that responses in V3A are little affected by low-level image covariates, and have a partial tolerance to the overall depth position. Finally, we show that responses in V3A parallel perceptual judgments of slant. This reveals a relatively short computational hierarchy that captures key information about the 3-D structure of nearby surfaces, and more generally demonstrates an analysis approach that may be of merit in a diverse range of brain imaging domains. PMID- 26156986 TI - Population Receptive Field Estimation Reveals New Retinotopic Maps in Human Subcortex. AB - The human subcortex contains multiple nuclei that govern the transmission of information to and among cortical areas. In the visual domain, these nuclei are organized into retinotopic maps. Because of their small size, these maps have been difficult to precisely measure using phase-encoded functional magnetic resonance imaging, particularly in the eccentricity dimension. Using instead the population receptive field model to estimate the response properties of individual voxels, we were able to resolve two previously unreported retinotopic maps in the thalamic reticular nucleus and the substantia nigra. We measured both the polar angle and eccentricity components, receptive field size and hemodynamic response function delay, in the these nuclei and in the lateral geniculate nucleus, the superior colliculus, and the lateral and intergeniculate pulvinars. The anatomical boundaries of these nuclei were delineated using multiple averaged proton density-weighted images and were used to constrain and confirm the functional activations. Deriving the retinotopic organization of these small, subcortical nuclei is the first step in exploring their response properties and their roles in neural dynamics. PMID- 26156987 TI - The Anatomical and Functional Organization of the Human Visual Pulvinar. AB - The pulvinar is the largest nucleus in the primate thalamus and contains extensive, reciprocal connections with visual cortex. Although the anatomical and functional organization of the pulvinar has been extensively studied in old and new world monkeys, little is known about the organization of the human pulvinar. Using high-resolution functional magnetic resonance imaging at 3 T, we identified two visual field maps within the ventral pulvinar, referred to as vPul1 and vPul2. Both maps contain an inversion of contralateral visual space with the upper visual field represented ventrally and the lower visual field represented dorsally. vPul1 and vPul2 border each other at the vertical meridian and share a representation of foveal space with iso-eccentricity lines extending across areal borders. Additional, coarse representations of contralateral visual space were identified within ventral medial and dorsal lateral portions of the pulvinar. Connectivity analyses on functional and diffusion imaging data revealed a strong distinction in thalamocortical connectivity between the dorsal and ventral pulvinar. The two maps in the ventral pulvinar were most strongly connected with early and extrastriate visual areas. Given the shared eccentricity representation and similarity in cortical connectivity, we propose that these two maps form a distinct visual field map cluster and perform related functions. The dorsal pulvinar was most strongly connected with parietal and frontal areas. The functional and anatomical organization observed within the human pulvinar was similar to the organization of the pulvinar in other primate species. SIGNIFICANCE STATEMENT: The anatomical organization and basic response properties of the visual pulvinar have been extensively studied in nonhuman primates. Yet, relatively little is known about the functional and anatomical organization of the human pulvinar. Using neuroimaging, we found multiple representations of visual space within the ventral human pulvinar and extensive topographically organized connectivity with visual cortex. This organization is similar to other nonhuman primates and provides additional support that the general organization of the pulvinar is consistent across the primate phylogenetic tree. These results suggest that the human pulvinar, like other primates, is well positioned to regulate corticocortical communication. PMID- 26156988 TI - Neural Correlate of the Thatcher Face Illusion in a Monkey Face-Selective Patch. AB - Compelling evidence that our sensitivity to facial structure is conserved across the primate order comes from studies of the "Thatcher face illusion": humans and monkeys notice changes in the orientation of facial features (e.g., the eyes) only when faces are upright, not when faces are upside down. Although it is presumed that face perception in primates depends on face-selective neurons in the inferior temporal (IT) cortex, it is not known whether these neurons respond differentially to upright faces with inverted features. Using microelectrodes guided by functional MRI mapping, we recorded cell responses in three regions of monkey IT cortex. We report an interaction in the middle lateral face patch (ML) between the global orientation of a face and the local orientation of its eyes, a response profile consistent with the perception of the Thatcher illusion. This increased sensitivity to eye orientation in upright faces resisted changes in screen location and was not found among face-selective neurons in other areas of IT cortex, including neurons in another face-selective region, the anterior lateral face patch. We conclude that the Thatcher face illusion is correlated with a pattern of activity in the ML that encodes faces according to a flexible holistic template. PMID- 26156989 TI - Neuronal Differentiation in Schwann Cell Lineage Underlies Postnatal Neurogenesis in the Enteric Nervous System. AB - Elucidation of the cellular identity of neuronal precursors provides mechanistic insights into the development and pathophysiology of the nervous system. In the enteric nervous system (ENS), neurogenesis persists from midgestation to the postnatal period. Cellular mechanism underlying the long-term neurogenesis in the ENS has remained unclear. Using genetic fate mapping in mice, we show here that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate in the postnatal period and contributes to the ENS. We found SCP-derived neurogenesis in the submucosal region of the small intestine in the absence of vagal neural crest-derived ENS precursors. Under physiological conditions, SCPs comprised up to 20% of enteric neurons in the large intestine and gave rise mainly to restricted neuronal subtypes, calretinin-expressing neurons. Genetic ablation of Ret, the signaling receptor for glial cell line-derived neurotrophic factor, in SCPs caused colonic oligoganglionosis, indicating that SCP-derived neurogenesis is essential to ENS integrity. Identification of Schwann cells as a physiological neurogenic source provides novel insight into the development and disorders of neural crest-derived tissues. SIGNIFICANCE STATEMENT: Elucidating the cellular identity of neuronal precursors provides novel insights into development and function of the nervous system. The enteric nervous system (ENS) is innervated richly by extrinsic nerve fibers, but little is known about the significance of extrinsic innervation to the structural integrity of the ENS. This report reveals that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate and differentiates into specific neuronal subtypes. SCP specific ablation of the Ret gene leads to colonic oligoganglionosis, demonstrating a crucial role of SCP-derived neurogenesis in ENS development. Cross-lineage differentiation capacity in SCPs suggests their potential involvement in the development and pathology of a wide variety of neural crest derived cell types. PMID- 26156990 TI - Network Anisotropy Trumps Noise for Efficient Object Coding in Macaque Inferior Temporal Cortex. AB - How neuronal ensembles compute information is actively studied in early visual cortex. Much less is known about how local ensembles function in inferior temporal (IT) cortex, the last stage of the ventral visual pathway that supports visual recognition. Previous reports suggested that nearby neurons carry information mostly independently, supporting efficient processing (Barlow, 1961). However, others postulate that noise covariation effects may depend on network anisotropy/homogeneity and on how the covariation relates to representation. Do slow trial-by-trial noise covariations increase or decrease IT's object coding capability, how does encoding capability relate to correlational structure (i.e., the spatial pattern of signal and noise redundancy/homogeneity across neurons), and does knowledge of correlational structure matter for decoding? We recorded simultaneously from ~80 spiking neurons in ~1 mm(3) of macaque IT under light neurolept anesthesia. Noise correlations were stronger for neurons with correlated tuning, and noise covariations reduced object encoding capability, including generalization across object pose and illumination. Knowledge of noise covariations did not lead to better decoding performance. However, knowledge of anisotropy/homogeneity improved encoding and decoding efficiency by reducing the number of neurons needed to reach a given performance level. Such correlated neurons were found mostly in supragranular and infragranular layers, supporting theories that link recurrent circuitry to manifold representation. These results suggest that redundancy benefits manifold learning of complex high-dimensional information and that subsets of neurons may be more immune to noise covariation than others. SIGNIFICANCE STATEMENT: How noise affects neuronal population coding is poorly understood. By sampling densely from local populations supporting visual object recognition, we show that recurrent circuitry supports useful representations and that subsets of neurons may be more immune to noise covariation than others. PMID- 26156991 TI - Glucose Induces Slow-Wave Sleep by Exciting the Sleep-Promoting Neurons in the Ventrolateral Preoptic Nucleus: A New Link between Sleep and Metabolism. AB - Sleep-active neurons located in the ventrolateral preoptic nucleus (VLPO) play a crucial role in the induction and maintenance of slow-wave sleep (SWS). However, the cellular and molecular mechanisms responsible for their activation at sleep onset remain poorly understood. Here, we test the hypothesis that a rise in extracellular glucose concentration in the VLPO can promote sleep by increasing the activity of sleep-promoting VLPO neurons. We find that infusion of a glucose concentration into the VLPO of mice promotes SWS and increases the density of c Fos-labeled neurons selectively in the VLPO. Moreover, we show in patch-clamp recordings from brain slices that VLPO neurons exhibiting properties of sleep promoting neurons are selectively excited by glucose within physiological range. This glucose-induced excitation implies the catabolism of glucose, leading to a closure of ATP-sensitive potassium (KATP) channels. The extracellular glucose concentration monitors the gating of KATP channels of sleep-promoting neurons, highlighting that these neurons can adapt their excitability according to the extracellular energy status. Together, these results provide evidence that glucose may participate in the mechanisms of SWS promotion and/or consolidation. SIGNIFICANCE STATEMENT: Although the brain circuitry underlying vigilance states is well described, the molecular mechanisms responsible for sleep onset remain largely unknown. Combining in vitro and in vivo experiments, we demonstrate that glucose likely contributes to sleep onset facilitation by increasing the excitability of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO). We find here that these neurons integrate energetic signals such as ambient glucose directly to regulate vigilance states accordingly. Glucose induced excitation of sleep-promoting VLPO neurons should therefore be involved in the drowsiness that one feels after a high-sugar meal. This novel mechanism regulating the activity of VLPO neurons reinforces the fundamental and intimate link between sleep and metabolism. PMID- 26156992 TI - Attentional Selection of Feature Conjunctions Is Accomplished by Parallel and Independent Selection of Single Features. AB - Experiments that study feature-based attention have often examined situations in which selection is based on a single feature (e.g., the color red). However, in more complex situations relevant stimuli may not be set apart from other stimuli by a single defining property but by a specific combination of features. Here, we examined sustained attentional selection of stimuli defined by conjunctions of color and orientation. Human observers attended to one out of four concurrently presented superimposed fields of randomly moving horizontal or vertical bars of red or blue color to detect brief intervals of coherent motion. Selective stimulus processing in early visual cortex was assessed by recordings of steady state visual evoked potentials (SSVEPs) elicited by each of the flickering fields of stimuli. We directly contrasted attentional selection of single features and feature conjunctions and found that SSVEP amplitudes on conditions in which selection was based on a single feature only (color or orientation) exactly predicted the magnitude of attentional enhancement of SSVEPs when attending to a conjunction of both features. Furthermore, enhanced SSVEP amplitudes elicited by attended stimuli were accompanied by equivalent reductions of SSVEP amplitudes elicited by unattended stimuli in all cases. We conclude that attentional selection of a feature-conjunction stimulus is accomplished by the parallel and independent facilitation of its constituent feature dimensions in early visual cortex. SIGNIFICANCE STATEMENT: The ability to perceive the world is limited by the brain's processing capacity. Attention affords adaptive behavior by selectively prioritizing processing of relevant stimuli based on their features (location, color, orientation, etc.). We found that attentional mechanisms for selection of different features belonging to the same object operate independently and in parallel: concurrent attentional selection of two stimulus features is simply the sum of attending to each of those features separately. This result is key to understanding attentional selection in complex (natural) scenes, where relevant stimuli are likely to be defined by a combination of stimulus features. PMID- 26156993 TI - Evolution of Network Synchronization during Early Epileptogenesis Parallels Synaptic Circuit Alterations. AB - In secondary epilepsy, a seizure-prone neural network evolves during the latent period between brain injury and the onset of spontaneous seizures. The nature of the evolution is largely unknown, and even its completeness at the onset of seizures has recently been challenged by measures of gradually decreasing intervals between subsequent seizures. Sequential calcium imaging of neuronal activity, in the pyramidal cell layer of mouse hippocampal in vitro preparations, during early post-traumatic epileptogenesis demonstrated rapid increases in the fraction of neurons that participate in interictal activity. This was followed by more gradual increases in the rate at which individual neurons join each developing seizure, the pairwise correlation of neuronal activities as a function of the distance separating the pair, and network-wide measures of functional connectivity. These data support the continued evolution of synaptic connectivity in epileptic networks beyond the latent period: early seizures occur when recurrent excitatory pathways are largely polysynaptic, while ongoing synaptic remodeling after the onset of epilepsy enhances intranetwork connectivity as well as the onset and spread of seizure activity. PMID- 26156994 TI - Disrupted Saccadic Corollary Discharge in Schizophrenia. AB - Disruptions in corollary discharge (CD), motor signals that send information to sensory areas and allow for prediction of sensory states, are argued to underlie the perceived loss of agency in schizophrenia. Behavioral and neurophysiological evidence for CD in primates comes largely from the saccadic double-step task, which requires participants to make two visually triggered saccadic eye movements in brief succession. Healthy individuals use CD to anticipate the change in eye position resulting from the first saccade when preparing the second saccade. In the current study with human participants, schizophrenia patients and healthy controls of both sexes performed a modified double-step task. Most trials required a saccade to a single visual target (T1). On a subset of trials, a second target (T2) was flashed shortly following T1. Subjects were instructed to look directly at T2. Healthy individuals also use CD to make rapid, corrective responses following erroneous saccades to T1. To assess CD in schizophrenia, we examined the following on error trials: (1) frequency and latency of corrective saccades, and (2) mislocalization of the corrective (second) saccade in the direction predicted by a failure to use CD to account for the first eye movement. Consistent with disrupted CD, patients made fewer and slower error corrections. Importantly, the corrective saccade vector angle was biased in a manner consistent with disrupted CD. These results provide novel and clear evidence for dysfunctional CD in the oculomotor system in patients with schizophrenia. Based on neurophysiology work, these disturbances might have their basis in medial thalamus dysfunction. SIGNIFICANCE STATEMENT: According to the World Health Organization, acute schizophrenia carries more disability weight than any other disease, but its etiology remains unknown. One promising theory of schizophrenia highlights alterations in a sense of self, in which self-generated thoughts or actions are attributed externally. Disruptions in corollary discharge (CD), motor signals sent to sensory areas that allow for the prediction of impending sensations, are proposed to underlie these symptoms. Direct physiological evidence, however, is limited. In nonhuman primates, inactivation of mediodorsal thalamic neurons disrupts CD associated with eye movements. Using the same task, we show similar impairments in schizophrenia patients, consistent with disrupted CD. These findings allow us to link clinical phenomenology to primate neurophysiology and interpret findings within a biological framework. PMID- 26156995 TI - Phasic Dopamine Modifies Sensory-Driven Output of Striatal Neurons through Synaptic Plasticity. AB - Animals are facing a complex sensory world in which only few stimuli are relevant to guide behavior. Value has to be assigned to relevant stimuli such as odors to select them over concurring information. Phasic dopamine is involved in the value assignment to stimuli in the ventral striatum. The underlying cellular mechanisms are incompletely understood. In striatal projection neurons of the ventral striatum in adult mice, we therefore examined the features and dynamics of phasic dopamine-induced synaptic plasticity and how this plasticity may modify the striatal output. Phasic dopamine is predicted to tag inputs that occur in temporal proximity. Indeed, we observed D1 receptor-dependent synaptic potentiation only when odor-like bursts and optogenetically evoked phasic dopamine release were paired within a time window of <1 s. Compatible with predictions of dynamic value assignment, the synaptic potentiation persisted after the phasic dopamine signal had ceased, but gradually reversed when odor like bursts continued to be presented. The synaptic plasticity depended on the sensory input rate and was input specific. Importantly, synaptic plasticity amplified the firing response to a given olfactory input as the dendritic integration and the firing threshold remained unchanged during synaptic potentiation. Thus, phasic dopamine-induced synaptic plasticity can change information transfer through dynamic increases of the output of striatal projection neurons to specific sensory inputs. This plasticity may provide a neural substrate for dynamic value assignment in the striatum. PMID- 26156996 TI - Chronic Back Pain Is Associated with Alterations in Dopamine Neurotransmission in the Ventral Striatum. AB - Back pain is common in the general population, but only a subgroup of back pain patients develops a disabling chronic pain state. The reasons for this are incompletely understood, but recent evidence implies that both preexisting and pain-related variations in the structure and function of the nervous system may contribute significantly to the development of chronic pain. Here, we addressed the role of striatal dopamine (DA) D2/D3 receptor (D2/D3R) function in chronic non-neuropathic back pain (CNBP) by comparing CNBP patients and healthy controls using PET and the D2/D3R-selective radioligand [(11)C]raclopride. D2/D3R availability was measured at baseline and during a pain challenge, yielding in vivo measures of receptor availability (binding potential, BPND) and DA release (change in BPND from baseline to activated state). At baseline, CNBP patients demonstrated reductions in D2/D3R BPND in the ventral striatum compared with controls. These reductions were associated with greater positive affect scores and pain tolerance measures. The reductions in D2/D3R BPND were also correlated with MU-opioid receptor BPND and pain-induced endogenous opioid system activation in the amygdala, further associated with measures of positive affect, the affective component of back pain and pain tolerance. During the pain challenge, lower magnitudes of DA release, and therefore D2/D3R activation, were also found in the ventral striatum in the CNBP sample compared with controls. Our results show that CNBP is associated with adaptations in ventral striatal D2/D3R function, which, together with endogenous opioid system function, contribute to the sensory and affective-motivational features of CNBP. SIGNIFICANCE STATEMENT: The neural systems that underlie chronic pain remain poorly understood. Here, using PET, we provide insight into the molecular mechanisms that regulate sensory and affective dimensions of pain in chronic back pain patients. We found that patients with back pain have alterations in brain dopamine function that are associated with measures of pain sensitivity and affective state, but also with brain endogenous opioid system functional measures. These findings suggest that brain dopamine-opioid interactions are involved in the pathophysiology of chronic pain, which has potential therapeutic implications. Our results may also help to explain individual variation in susceptibility to opioid medication misuse and eventual addiction in the context of chronic pain. PMID- 26156997 TI - Toll-Like Receptors and Dectin-1, a C-Type Lectin Receptor, Trigger Divergent Functions in CNS Macrophages. AB - Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid macrophage reaction; however, only dectin-1 activation causes macrophage-mediated demyelination and axonal injury. Coactivating TLR2 reduced the injurious effects of dectin-1 activation. When injected into traumatically injured spinal cord, TLR2 agonists enhance the endogenous macrophage reaction while conferring neuroprotection. Indeed, dieback of axons was reduced, leading to smaller lesion volumes at the peak of the macrophage response. Moreover, the density of NG2+ cells expressing vimentin increased in and near lesions that were enriched with TLR2-activated macrophages. In dectin-1-null mutant (knock-out) mice, dieback of corticospinal tract axons also is reduced after SCI. Collectively, these data support the hypothesis that the ability of macrophages to create an axon growth permissive microenvironment or cause neurotoxicity is receptor dependent and it may be possible to exploit this functional dichotomy to enhance CNS repair. SIGNIFICANCE STATEMENT: There is a growing appreciation that macrophages exert diverse functions in the injured and diseased CNS. Indeed, both macrophage mediated repair and macrophage-mediated injury occur, and often these effector functions are elicited simultaneously. Understanding the mechanisms governing the reparative and pathological properties of activated macrophages is at the forefront of neuroscience research. In this report, using in vitro and in vivo models of relevance to traumatic spinal cord injury (SCI), new data indicate that stochastic activation of toll-like and c-type lectin receptors on macrophages causes neuroprotection or neurotoxicity, respectively. Although this manuscript focuses on SCI, these two innate immune receptor subtypes are also involved in developmental processes and become activated in macrophages that respond to various neurological diseases. PMID- 26157000 TI - Deep Neural Networks Reveal a Gradient in the Complexity of Neural Representations across the Ventral Stream. AB - Converging evidence suggests that the primate ventral visual pathway encodes increasingly complex stimulus features in downstream areas. We quantitatively show that there indeed exists an explicit gradient for feature complexity in the ventral pathway of the human brain. This was achieved by mapping thousands of stimulus features of increasing complexity across the cortical sheet using a deep neural network. Our approach also revealed a fine-grained functional specialization of downstream areas of the ventral stream. Furthermore, it allowed decoding of representations from human brain activity at an unsurpassed degree of accuracy, confirming the quality of the developed approach. Stimulus features that successfully explained neural responses indicate that population receptive fields were explicitly tuned for object categorization. This provides strong support for the hypothesis that object categorization is a guiding principle in the functional organization of the primate ventral stream. PMID- 26156998 TI - Elimination of Microglia Improves Functional Outcomes Following Extensive Neuronal Loss in the Hippocampus. AB - With severe injury or disease, microglia become chronically activated and damage the local brain environment, likely contributing to cognitive decline. We previously discovered that microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for survival in the healthy adult brain, and we have exploited this dependence to determine whether such activated microglia contribute deleteriously to functional recovery following a neuronal lesion. Here, we induced a hippocampal lesion in mice for 25 d via neuronal expression of diphtheria toxin A-chain, producing both a neuroinflammatory reaction and behavioral alterations. Following the 25 d lesion, we administered PLX3397, a CSF1R inhibitor, for 30 d to eliminate microglia. This post-lesion treatment paradigm improved functional recovery on elevated plus maze and Morris water maze, concomitant with reductions in elevated proinflammatory molecules, as well as normalization of lesion-induced alterations in synaptophysin and PSD-95. Further exploration of the effects of microglia on synapses in a second cohort of mice revealed that dendritic spine densities are increased with long-term microglial elimination, providing evidence that microglia shape the synaptic landscape in the adult mouse brain. Furthermore, in these same animals, we determined that microglia play a protective role during lesioning, whereby neuronal loss was potentiated in the absence of these cells. Collectively, we demonstrate that microglia exert beneficial effects during a diphtheria toxin induced neuronal lesion, but impede recovery following insult. SIGNIFICANCE STATEMENT: It remains unknown to what degree, and by what mechanisms, chronically activated microglia contribute to cognitive deficits associated with brain insults. We induced a genetic neuronal lesion in mice for 25 d and found activated microglia to increase inflammation, alter synaptic surrogates, and impede behavioral recovery. These lesion-associated deficits were ameliorated with subsequent microglial elimination, underscoring the importance of developing therapeutics aimed at eliminating/modulating chronic microglial activation. Additionally, we found long-term microglial depletion globally increases dendritic spines by ~35% in the adult brain, indicating that microglia continue to sculpt the synaptic landscape in the postdevelopmental brain under homeostatic conditions. Microglial manipulation can therefore be used to investigate the utility of increasing dendritic spine numbers in postnatal conditions displaying synaptic aberrations. PMID- 26156999 TI - DOP-2 D2-Like Receptor Regulates UNC-7 Innexins to Attenuate Recurrent Sensory Motor Neurons during C. elegans Copulation. AB - Neuromodulation of self-amplifying circuits directs context-dependent behavioral executions. Although recurrent networks are found throughout the Caenorhabditis elegans connectome, few reports describe the mechanisms that regulate reciprocal neural activity during complex behavior. We used C. elegans male copulation to dissect how a goal-oriented motor behavior is regulated by recurrently wired sensory-motor neurons. As the male tail presses against the hermaphrodite's vulva, cholinergic and glutamatergic reciprocal innervations of post cloaca sensilla (PCS) neurons (PCA, PCB, and PCC), hook neurons (HOA, HOB), and their postsynaptic sex muscles execute rhythmic copulatory spicule thrusts. These repetitive spicule movements continue until the male shifts off the vulva or genital penetration is accomplished. However, the signaling mechanism that temporally and spatially restricts repetitive intromission attempts to vulva cues was unclear. Here, we report that confinement of spicule insertion attempts to the vulva is facilitated by D2-like receptor modulation of gap-junctions between PCB and the hook sensillum. We isolated a missense mutation in the UNC-7(L) gap junction isoform, which perturbs DOP-2 signaling in the PCB neuron and its electrical partner, HOA. The glutamate-gated chloride channel AVR-14 is expressed in HOA. Our analysis of the unc-7 mutant allele indicates that when DOP-2 promotes UNC-7 electrical communication, AVR-14-mediated inhibitory signals pass from HOA to PCB. As a consequence, PCB is less receptive to be stimulated by its recurrent synaptic partner, PCA. Behavioral observations suggest that dopamine neuromodulation of UNC-7 ensures attenuation of recursive intromission attempts when the male disengages or is dislodged from the hermaphrodite genitalia. SIGNIFICANCE STATEMENT: Using C. elegans male copulation as a model, we found that the neurotransmitter dopamine stimulates D2-like receptors in two sensory circuits to terminate futile behavioral loops. The D2-like receptors promote inhibitory electrical junction activity between a chemosensory and a mechanosensory circuit. Therefore, both systems are attenuated and the animal ceases the recursive behavior. PMID- 26157001 TI - Disrupted Frontoparietal Network Mediates White Matter Structure Dysfunction Associated with Cognitive Decline in Hypertension Patients. AB - Some previous reports have suggested that hypertension is a risk factor for dementia and cognitive impairments. Using behavioral data from 1007 elderly human subjects (405 hypertensive patients) of Han ethnicity from Beijing, China, the present study aimed to assess the effects of hypertension on cognitive performance and explore related neuronal changes via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data from 84 of these subjects (44 hypertensive patients). Cognitively, we found that patients with hypertension showed decreased executive functions and attention compared with those with normotension in the large sample. In magnetic resonance imaging scan sample, using independent component analysis to examine the functional connectivity difference between the two groups, we found that the frontoparietal networks in the hypertensive group exhibited altered patterns compared with the control group, mainly in the inferior parietal lobe, left inferior frontal lobe, and precuneus. Using tract-based spatial statistics to investigate the between group structural difference, we found that the hypertensive group showed significantly reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, using the mediation analysis, we found that the functional connectivity of the frontoparietal networks mediates the impact of white matter on executive function in the hypertensive group. The results demonstrate that hypertension targets a specific pattern of cognitive decline, possibly due to deficits in the white matter and functional connectivity in frontal and parietal lobes. Our findings highlight the importance of brain protection in hypertension. SIGNIFICANCE STATEMENT: Hypertension is a risk factor for cognitive decline and dementia. However, the neural mechanism underlying cognitive decline in hypertension is largely unknown. We studied the relationship among cognitive decline, brain functional, and structural changes in hypertensive patients via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data in a Chinese cohort. Hypertensive patients showed executive dysfunction, along with disrupted functional connectivity in frontoparietal (FP) networks and reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, the functional connectivity changes mediate the impact of white matter alterations on cognitive decline in the hypertensive group. Our findings provide a better understanding of the mechanism of cognitive decline in hypertension and highlight the importance of brain protection in hypertension. PMID- 26157002 TI - Integration of Multiple Spatial Frequency Channels in Disparity-Sensitive Neurons in the Primary Visual Cortex. AB - For our vivid perception of a 3-D world, the stereoscopic function begins in our brain by detecting slight shifts of image features between the two eyes, called binocular disparity. The primary visual cortex is the first stage of this processing, and neurons there are tuned to a limited range of spatial frequencies (SFs). However, our visual world is generally highly complex, composed of numerous features at a variety of scales, thereby having broadband SF spectra. This means that binocular information signaled by individual neurons is highly incomplete, and combining information across multiple SF bands must be essential for the visual system to function in a robust and reliable manner. In this study, we investigated whether the integration of information from multiple SF channels begins in the cat primary visual cortex. We measured disparity-selective responses in the joint left-right SF domain using sequences of dichoptically flashed grating stimuli consisting of various combinations of SFs and phases. The obtained interaction map in the joint SF domain reflects the degree of integration across different SF channels. Our data are consistent with the idea that disparity information is combined from multiple SF channels in a substantial fraction of complex cells. Furthermore, for the majority of these neurons, the optimal disparity is matched across the SF bands. These results suggest that a highly specific SF integration process for disparity detection starts in the primary visual cortex. SIGNIFICANCE STATEMENT: Our visual world is broadband, containing features with a wide range of object scales. On the other hand, single neurons in the primary visual cortex are narrow-band, being tuned narrowly for a specific scale. For robust visual perception, narrow-band information of single neurons must be integrated eventually at some stage. We have examined whether such an integration process begins in the primary visual cortex with respect to binocular processing. The results suggest that a subset of cells appear to combine binocular information across multiple scales. Furthermore, for the majority of these neurons, an optimal parameter of binocular tuning is matched across multiple scales, suggesting the presence of a highly specific neural integration mechanism. PMID- 26157005 TI - Local Circuits for Contrast Normalization and Adaptation Investigated with Two Photon Imaging in Cat Primary Visual Cortex. AB - Sensory neurons encode stimulus intensity in their instantaneous spike rate and adjust the set-points of the stimulus-response relationships by adaptation. In the visual cortex, adaptation is crucial because the mechanism of fast gain control (normalization) increases the contrast sensitivity of individual neurons at the cost of encoding a far narrower range of contrasts than is encountered in natural scenes. The mechanism of adaptation, however, is a slow process and has a time constant of seconds. Here we use two-photon calcium imaging of identified excitatory and inhibitory neurons in superficial layers of cat primary visual cortex to answer two questions: for a given set-point, what is range of contrasts represented within a local pool of neurons, and what accounts for the slow time constant of contrast adaptation? We found that a local patch of excitatory neurons has a large diversity of contrast tunings, which effectively extends the range of contrast that can be encoded instantaneously in cortex. Additionally, we identified a pool of parvalbumin-positive GABAergic neurons and neurons in the upper tier of imaging sites that showed a paradoxical slow increase in activity during adaptation, thus implicating them in the slow set-point adaptation of the excitatory population. Our results provide new insights into the circuits and mechanisms underlying cortical adaptation and gain control. SIGNIFICANCE STATEMENT: Neurons in the primary visual cortex (V1) respond near instantaneously over a limited range of contrasts but can also shift their operating range according to the average contrast of the scene. This "contrast adaptation" takes 5-10 s and ensures that a full range of contrasts can be encoded in V1, while remaining sensitive to small changes in local contrast. By optically recording many layer 2 neurons simultaneously, we discovered that networks of neurons collectively code for a much wider range of contrasts. Whereas most neurons responded to sustained increases in contrast by decreasing their spike firing rates, two types of inhibitory neurons in the cat's visual cortex paradoxically increased their firing rates and so could inhibit other neurons to produce contrast adaptation. PMID- 26157006 TI - Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling. AB - Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. SIGNIFICANCE STATEMENT: Since the early 2000s, functional MRI (fMRI) has demonstrated profound modifications in the recruitment of cortical areas during motor, cognitive, and sensory tasks in multiple sclerosis (MS) patients. Experimental autoimmune encephalomyelitis (EAE) represents a reliable model of the chronic-progressive variant of MS. fMRI studies in EAE have not been performed extensively up to now. This paper reports fMRI studies in a rat model of MS with somatosensory stimulation of the forepaw. We demonstrated modifications in the recruitment of cortical areas consistent with data from MS patients. To the best of our knowledge, this is the first report of cortical remodeling in a preclinical in vivo model of MS. PMID- 26157004 TI - Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson's Disease. AB - Sustained neuroinflammation mediated by resident microglia is recognized as a key pathophysiological contributor to many neurodegenerative diseases, including Parkinson's disease (PD), but the key molecular signaling events regulating persistent microglial activation have yet to be clearly defined. In the present study, we examined the role of Fyn, a non-receptor tyrosine kinase, in microglial activation and neuroinflammatory mechanisms in cell culture and animal models of PD. The well-characterized inflammogens LPS and TNFalpha rapidly activated Fyn kinase in microglia. Immunocytochemical studies revealed that activated Fyn preferentially localized to the microglial plasma membrane periphery and the nucleus. Furthermore, activated Fyn phosphorylated PKCdelta at tyrosine residue 311, contributing to an inflammogen-induced increase in its kinase activity. Notably, the Fyn-PKCdelta signaling axis further activated the LPS- and TNFalpha induced MAP kinase phosphorylation and activation of the NFkappaB pathway, implying that Fyn is a major upstream regulator of proinflammatory signaling. Functional studies in microglia isolated from wild-type (Fyn(+/+)) and Fyn knock out (Fyn(-/-)) mice revealed that Fyn is required for proinflammatory responses, including cytokine release as well as iNOS activation. Interestingly, a prolonged inflammatory insult induced Fyn transcript and protein expression, indicating that Fyn is upregulated during chronic inflammatory conditions. Importantly, in vivo studies using MPTP, LPS, or 6-OHDA models revealed a greater attenuation of neuroinflammatory responses in Fyn(-/-) and PKCdelta (-/-) mice compared with wild-type mice. Collectively, our data demonstrate that Fyn is a major upstream signaling mediator of microglial neuroinflammatory processes in PD. SIGNIFICANCE STATEMENT: Parkinson's disease (PD) is a complex multifactorial disease characterized by the progressive loss of midbrain dopamine neurons. Sustained microglia-mediated neuroinflammation has been recognized as a major pathophysiological contributor to chronic degenerative processes in PD; however, the key molecular signaling mechanisms underlying microglial activation are not entirely clear. Herein, we identified a novel role for the non-receptor tyrosine kinase Fyn in regulating neuroinflammatory responses in microglia. Our data clearly suggest that the Fyn-PKCdelta signaling axis acts as a major upstream signaling mediator of the sustained neuroinflammatory processes in cell culture and animal models of PD. Our finding has important clinical significance to PD because it identifies Fyn as a potential translational target for intervention of progressive neurodegenerative processes in PD. PMID- 26157007 TI - Matriptase activation and shedding through PDGF-D-mediated extracellular acidosis. AB - Activation of beta-platelet-derived growth factor receptor (beta-PDGFR) is associated with prostate cancer (PCa) progression and recurrence after prostatectomy. Analysis of the beta-PDGFR ligands in PCa revealed association between PDGF-D expression and Gleason score as well as tumor stage. During the course of studying the functional consequences of PDGF ligand-specific beta-PDGFR signaling in PCa, we discovered a novel function of PDGF-D for activation/shedding of the serine protease matriptase leading to cell invasion, migration, and tumorigenesis. The present study showed that PDGF-D, not PDGF-B, induces extracellular acidification, which correlates with increased matriptase activation. A cDNA microarray analysis revealed that PDGF-D/beta-PDGFR signaling upregulates expression of the acidosis regulator carbonic anhydrase IX (CAIX), a classic target of the transcriptional factor hypoxia-inducible factor-1alpha (HIF 1alpha). Cellular fractionation displayed a strong HIF-1alpha nuclear localization in PDGF-D-expressing cells. Treatment of vector control or PDGF-B expressing cells with the HIF-1alpha activator CoCl2 led to increased CAIX expression accompanied by extracellular acidosis and matriptase activation. Furthermore, the analysis of the CAFTD cell lines, variants of the BPH-1 transformation model, showed that increased PDGF-D expression is associated with enhanced HIF-1alpha activity, CAIX induction, cellular acidosis, and matriptase shedding. Importantly, shRNA-mediated knockdown of CAIX expression effectively reversed extracellular acidosis and matriptase activation in PDGF-D-transfected BPH-1 cells and in CAFTD variants that express endogenous PDGF-D at a high level. Taken together, these novel findings reveal a new paradigm in matriptase activation involving PDGF-D-specific signal transduction leading to extracellular acidosis. PMID- 26157003 TI - Multiple Forms of Endocannabinoid and Endovanilloid Signaling Regulate the Tonic Control of GABA Release. AB - Persistent CB1 cannabinoid receptor activity limits neurotransmitter release at various synapses throughout the brain. However, it is not fully understood how constitutively active CB1 receptors, tonic endocannabinoid signaling, and its regulation by multiple serine hydrolases contribute to the synapse-specific calibration of neurotransmitter release probability. To address this question at perisomatic and dendritic GABAergic synapses in the mouse hippocampus, we used a combination of paired whole-cell patch-clamp recording, liquid chromatography/tandem mass spectrometry, stochastic optical reconstruction microscopy super-resolution imaging, and immunogold electron microscopy. Unexpectedly, application of the CB1 antagonist and inverse agonist AM251 [N-1 (2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3 carboxamide], but not the neutral antagonist NESS0327 [8-chloro-1-(2,4 dichlorophenyl)-N-piperidin-1-yl-5,6-dihydro-4H-benzo[2,3]cyclohepta[2,4 b]pyrazole-3-carboxamine], significantly increased synaptic transmission between CB1-positive perisomatic interneurons and CA1 pyramidal neurons. JZL184 (4 nitrophenyl 4-[bis(1,3-benzodioxol-5-yl)(hydroxy)methyl]piperidine-1 carboxylate), a selective inhibitor of monoacylglycerol lipase (MGL), the presynaptic degrading enzyme of the endocannabinoid 2-arachidonoylglycerol (2 AG), elicited a robust increase in 2-AG levels and concomitantly decreased GABAergic transmission. In contrast, inhibition of fatty acid amide hydrolase (FAAH) by PF3845 (N-pyridin-3-yl-4-[[3-[5-(trifluoromethyl)pyridin-2 yl]oxyphenyl]methyl]piperidine-1-carboxamide) elevated endocannabinoid/endovanilloid anandamide levels but did not change GABAergic synaptic activity. However, FAAH inhibitors attenuated tonic 2-AG increase and also decreased its synaptic effects. This antagonistic interaction required the activation of the transient receptor potential vanilloid receptor TRPV1, which was concentrated on postsynaptic intracellular membrane cisternae at perisomatic GABAergic symmetrical synapses. Interestingly, neither AM251, JZL184, nor PF3845 affected CB1-positive dendritic interneuron synapses. Together, these findings are consistent with the possibility that constitutively active CB1 receptors substantially influence perisomatic GABA release probability and indicate that the synaptic effects of tonic 2-AG release are tightly controlled by presynaptic MGL activity and also by postsynaptic endovanilloid signaling and FAAH activity. SIGNIFICANCE STATEMENT: Tonic cannabinoid signaling plays a critical role in the regulation of synaptic transmission. However, the mechanistic details of how persistent CB1 cannabinoid receptor activity inhibits neurotransmitter release have remained elusive. Therefore, electrophysiological recordings, lipid measurements, and super-resolution imaging were combined to elucidate those signaling molecules and mechanisms that underlie tonic cannabinoid signaling. The findings indicate that constitutive CB1 activity has pivotal function in the tonic control of hippocampal GABA release. Moreover, the endocannabinoid 2 arachidonoylglycerol (2-AG) is continuously generated postsynaptically, but its synaptic effect is regulated strictly by presynaptic monoacylglycerol lipase activity. Finally, anandamide signaling antagonizes tonic 2-AG signaling via activation of postsynaptic transient receptor potential vanilloid TRPV1 receptors. This unexpected mechanistic diversity may be necessary to fine-tune GABA release probability under various physiological and pathophysiological conditions. PMID- 26157008 TI - Ion dependence of Na-K-ATPase-mediated epithelial cell adhesion and migration. PMID- 26157009 TI - Lmo7 is dispensable for skeletal muscle and cardiac function. AB - Emery-Dreifuss muscular dystrophy (EDMD) is a degenerative disease primarily affecting skeletal muscles in early childhood as well as cardiac muscle at later stages. EDMD is caused by a number of mutations in genes encoding proteins associated with the nuclear envelope (e.g., Emerin, Lamin A/C, and Nesprin). Recently, a novel protein, Lim-domain only 7 (lmo7) has been reported to play a role in the molecular pathogenesis of EDMD. Prior in vitro and in vivo studies suggested the intriguing possibility that Lmo7 plays a role in skeletal or cardiac muscle pathophysiology. To further understand the in vivo role of Lmo7 in striated muscles, we generated a novel Lmo7-null (lmo7(-/-)) mouse line. Using this mouse line, we examined skeletal and cardiac muscle physiology, as well as the role of Lmo7 in a model of muscular dystrophy and regeneration using the dystrophin-deficient mdx mouse model. Our results demonstrated that lmo7(-/-) mice had no abnormalities in skeletal muscle morphology, physiological function, or regeneration. Cardiac function was also unaffected. Moreover, we found that ablation of lmo7 in mdx mice had no effect on the observed myopathy and muscular regeneration exhibited by mdx mice. Molecular analyses also showed no changes in dystrophin complex factors, MAPK pathway components, and Emerin levels in lmo7 knockout mice. Taken together, we conclude that Lmo7 is dispensable for skeletal muscle and cardiac physiology and pathophysiology. PMID- 26157010 TI - JNK-dependent gene regulatory circuitry governs mesenchymal fate. AB - The epithelial to mesenchymal transition (EMT) is a biological process in which cells lose cell-cell contacts and become motile. EMT is used during development, for example, in triggering neural crest migration, and in cancer metastasis. Despite progress, the dynamics of JNK signaling, its role in genomewide transcriptional reprogramming, and involved downstream effectors during EMT remain largely unknown. Here, we show that JNK is not required for initiation, but progression of phenotypic changes associated with EMT. Such dependency resulted from JNK-driven transcriptional reprogramming of critical EMT genes and involved changes in their chromatin state. Furthermore, we identified eight novel JNK-induced transcription factors that were required for proper EMT. Three of these factors were also highly expressed in invasive cancer cells where they function in gene regulation to maintain mesenchymal identity. These factors were also induced during neuronal development and function in neuronal migration in vivo. These comprehensive findings uncovered a kinetically distinct role for the JNK pathway in defining the transcriptome that underlies mesenchymal identity and revealed novel transcription factors that mediate these responses during development and disease. PMID- 26157011 TI - Dizziness and Unstable Gait in Old Age: Etiology, Diagnosis and Treatment. AB - BACKGROUND: Dizziness and unsteady gait are common in the elderly but are too often dismissed as supposedly nonspecific, inevitable accompaniments of normal aging. For many affected persons, the factors leading to dizziness and gait impairment in old age are never identified, yet some of these factors can be specifically detected and treated. METHODS: This review is based on publications (2005-2014) retrieved by a selective search in PubMed on the terms "aging," "dizziness," "elderly," "gait," "gait disorder," "geriatric," "locomotion," and "vertigo." RESULTS: Dizziness interferes with the everyday activities of 30% of persons over age 70 and is so severe that it constitutes a reason for consulting a physician. The more common causes of dizziness and unsteady gait in old age are sensory deficits, such as bilateral vestibular failure, polyneuropathy, and impaired visual acuity; benign paroxysmal positioning vertigo; and central disorders such as cerebellar ataxia and normal-pressure hydrocephalus. Further relevant factors include sedative or antihypertensive medication, loss of muscle mass (sarcopenia), and fear of falling. Many elderly persons have multiple factors at the same time. Benign paroxysmal positioning vertigo can be effectively treated with specific physical maneuvers. Sedating drugs are indicated only for the treatment of acute rotatory vertigo and are not suitable for long-term use. Sarcopenia can be treated with physical training. CONCLUSION: If a specific cause can be identified, dizziness and gait unsteadiness in old age can often be successfully treated. The common causes can be revealed by systematic clinical examination. Controlled clinical trials on the efficacy of treatments for elderly persons are urgently needed. PMID- 26157013 TI - Unanswered Questions. PMID- 26157012 TI - The Diagnosis, Risk Stratification, and Treatment of Brugada Syndrome. AB - BACKGROUND: Brugada syndrome (BrS) is among the more common familial arrhythmia syndromes, with an estimated prevalence of 1 to 5 per 10 000 persons. It is characterized by a right ventricular conduction delay, dynamic or persistent ST segment elevations in the precordial leads V1-3 , and an elevated risk of syncope and sudden cardiac death in young adults without structural heart disease. METHODS: This article is based on original and review articles on BrS that appeared in English from 2010 onward and were retrieved by a selective search in PubMed, with special attention to international consensus publications on inherited arrhythmogenic diseases. RESULTS: According to the new diagnostic criteria, the diagnosis of BrS requires typical ECG changes in only one precordial lead. This will likely increase sensitivity, but may also lead to an increase in asymptomatic patients. Established risk markers include sudden cardiac arrest and a spontaneous type 1 ECG with arrhythmic syncope. Patients with these findings benefit from the implantation of a cardioverter defibrillator. There is no validated algorithm for risk stratification of asymptomatic patients. Because of the low prevalence of BrS, there have been no randomized controlled trials (RCTs) in this disease, and all recommendations are based on expert opinion. BrS is usually inherited in an autosomal dominant manner. Recently discovered gene polymorphisms modify the risk of BrS, challenging the conception of BrS as a monogenetic disease. Electro-anatomic mapping studies have revealed, for the first time, an arrhythmogenic substrate over the right ventricular outflow tract in BrS patients. CONCLUSION: BrS is one important differential diagnosis to consider in patients presenting with syncope or sudden cardiac arrest. The goal of current research is to achieve a deeper understanding of the genetic and electrophysiological changes underlying BrS. Further insights in these areas will probably enable better risk stratification of asymptomatic BrS patients in the future. PMID- 26157014 TI - Greater Differentiation Would Have Been Desirable. PMID- 26157015 TI - Motivation Is Crucial for Immunization Success. PMID- 26157016 TI - In Reply. PMID- 26157017 TI - Open Biportal Decompression of the Median Nerve. PMID- 26157018 TI - In Reply. PMID- 26157019 TI - The Drosophila Pericentrin-like-protein (PLP) cooperates with Cnn to maintain the integrity of the outer PCM. AB - Centrosomes comprise a pair of centrioles surrounded by a matrix of pericentriolar material (PCM). In vertebrate cells, Pericentrin plays an important part in mitotic PCM assembly, but the Drosophila Pericentrin-like protein (PLP) appears to have a more minor role in mitotic fly cells. Here we investigate the function of PLP during the rapid mitotic cycles of the early Drosophila embryo. Unexpectedly, we find that PLP is specifically enriched in the outer-most regions of the PCM, where it largely co-localizes with the PCM scaffold protein Cnn. In the absence of PLP the outer PCM appears to be structurally weakened, and it rapidly disperses along the centrosomal microtubules (MTs). As a result, centrosomal MTs are subtly disorganized in embryos lacking PLP, although mitosis is largely unperturbed and these embryos develop and hatch at near-normal rates. Y2H analysis reveals that PLP can potentially form multiple interactions with itself and with the PCM recruiting proteins Asl, Spd-2 and Cnn. A deletion analysis suggests that PLP participates in a complex network of interactions that ultimately help to strengthen the PCM. PMID- 26157020 TI - Interaction of maternal smoking and preterm birth on future risk of maternal cardiovascular disease: A population-based record linkage study. AB - BACKGROUND: While associations of smoking and preterm birth (PTB) with maternal cardiovascular disease (CVD) risks have been established, it is unknown whether the coexistence of these two conditions could synergistically increase the risks. METHODS: We linked birth records of 902,008 mothers with singleton infants during 1994-2011 in New South Wales, Australia to the mothers' subsequent CVD hospitalisation or death. Multiplicative interaction was tested through an interaction term in a multivariate Cox-proportional hazard regression model, while additive interaction was assessed by calculating the synergy index. RESULTS: Relative to never-smokers with term babies, the CVD risk in ever-smokers with PTBs (hazard ratio (HR) 3.35, 95% confidence interval (CI) 2.96-3.80) was significantly greater than the sum of risks in ever-smokers with term babies (HR 2.10, 95% CI 1.96-2.24) and in never-smokers with PTBs (HR 1.73, 95% CI 1.55 1.93), indicating an additive interaction (synergy index = 1.29, 95% CI 1.05 1.58). In ever-smokers, the association was stronger for extremely PTB (HR 3.83, 95% CI 3.23-4.69) than moderately PTB (HR 3.18, 95% CI 2.76-3.66), and for >=2 PTB (HR 4.47, 95% CI 3.39-5.88) than one PTB (HR 3.20, 95% CI 2.81-3.64). CONCLUSION: Maternal smoking and PTB interact on the additive scale to synergistically increase maternal CVD risks. The interaction was dose-dependent according to both the severity and number of PTBs. PMID- 26157023 TI - Strategies for fine-mapping complex traits. AB - Genome-wide association studies (GWAS) have identified thousands of robust and replicable genetic associations for complex disease. However, the identification of the causal variants that underlie these associations has been more difficult. This problem of fine-mapping association signals predates GWAS, but the last few years have seen a surge of studies aimed at pinpointing causal variants using both statistical evidence from large association data sets and functional annotations of genetic variants. Combining these two approaches can often determine not only the causal variant but also the target gene. Recent contributions include analyses of custom genotyping arrays, such as the Immunochip, statistical methods to identify credible sets of causal variants and the addition of functional genomic annotations for coding and non-coding variation to help prioritize variants and discern functional consequence and hence the biological basis of disease risk. PMID- 26157024 TI - The CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort. AB - Myoclonus-dystonia (M-D) is a very rare movement disorder, caused in ~30-50% of cases by mutations in SGCE. The CACNA1B variant c.4166G>A; (p.R1389H) was recently reported as the likely causative mutation in a single 3-generation Dutch pedigree with five subjects affected by a unique dominant M-D syndrome and cardiac arrhythmias. In an attempt to replicate this finding, we assessed by direct sequencing the frequency of CACNA1B c.4166G>A; (p.R1389H) in a cohort of 520 M-D cases, in which SGCE mutations had been previously excluded. A total of 146 cases (28%) had a positive family history of M-D. The frequency of the variant was also assessed in 489 neurologically healthy controls and in publicly available data sets of genetic variation (1000 Genomes, Exome Variant Server and Exome Aggregation Consortium). The variant was detected in a single sporadic case with M-D, but in none of the 146 probands with familial M-D. Overall, the variant was present at comparable frequencies in M-D cases (1 out of 520; 0.19%) and healthy controls (1 out of 489; 0.2%). A similar frequency of the variant was also reported in all publicly available databases. These results do not support a causal association between the CACNA1B c.4166G>A; (p.R1389H) variant and M-D. PMID- 26157025 TI - Distinct but Overlapping Patterns of Response to Words and Faces in the Fusiform Gyrus. AB - Converging evidence suggests that the fusiform gyrus is involved in the processing of both faces and words. We used fMRI to investigate the extent to which the representation of words and faces in this region of the brain is based on a common neural representation. In Experiment 1, a univariate analysis revealed regions in the fusiform gyrus that were only selective for faces and other regions that were only selective for words. However, we also found regions that showed both word-selective and face-selective responses, particularly in the left hemisphere. We then used a multivariate analysis to measure the pattern of response to faces and words. Despite the overlap in regional responses, we found distinct patterns of response to both faces and words in the left and right fusiform gyrus. In Experiment 2, fMR adaptation was used to determine whether information about familiar faces and names is integrated in the fusiform gyrus. Distinct regions of the fusiform gyrus showed adaptation to either familiar faces or familiar names. However, there was no adaptation to sequences of faces and names with the same identity. Taken together, these results provide evidence for distinct, but overlapping, neural representations for words and faces in the fusiform gyrus. PMID- 26157027 TI - Stopping superbugs, maintaining the microbiota. AB - The U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria will succeed only if we alter the definition of "antibiotic." PMID- 26157026 TI - Hierarchical Organization of Auditory and Motor Representations in Speech Perception: Evidence from Searchlight Similarity Analysis. AB - How humans extract the identity of speech sounds from highly variable acoustic signals remains unclear. Here, we use searchlight representational similarity analysis (RSA) to localize and characterize neural representations of syllables at different levels of the hierarchically organized temporo-frontal pathways for speech perception. We asked participants to listen to spoken syllables that differed considerably in their surface acoustic form by changing speaker and degrading surface acoustics using noise-vocoding and sine wave synthesis while we recorded neural responses with functional magnetic resonance imaging. We found evidence for a graded hierarchy of abstraction across the brain. At the peak of the hierarchy, neural representations in somatomotor cortex encoded syllable identity but not surface acoustic form, at the base of the hierarchy, primary auditory cortex showed the reverse. In contrast, bilateral temporal cortex exhibited an intermediate response, encoding both syllable identity and the surface acoustic form of speech. Regions of somatomotor cortex associated with encoding syllable identity in perception were also engaged when producing the same syllables in a separate session. These findings are consistent with a hierarchical account of how variable acoustic signals are transformed into abstract representations of the identity of speech sounds. PMID- 26157028 TI - Erratum for the Research Article: "Integration of Hedgehog and mutant FLT3 signaling in myeloid leukemia" by Y. Lim, L. Gondek, L. Li, Q. Wang, H. Ma, E. Chang, D. L. Huso, S. Foerster, L. Marchionni, K. McGovern, D. N. Watkins, C. D. Peacock, M. Levis, B. D. Smith, A. A. Merchant, D. Small, W. Matsui. PMID- 26157029 TI - Gene therapy for deafness: How close are we? AB - Virus-mediated transfer of genes encoding the mechanotransducer channel candidates TMC1 and TMC2 into hair cells of the ear partially restores hearing in animal models of human genetic deafness (Askew et al., this issue). PMID- 26157030 TI - Tmc gene therapy restores auditory function in deaf mice. AB - Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mouse models of genetic deafness. We focused on DFNB7/11 and DFNA36, which are autosomal recessive and dominant deafnesses, respectively, caused by mutations in transmembrane channel-like 1 (TMC1). Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36. We screened several adeno-associated viral (AAV) serotypes and promoters and identified AAV2/1 and the chicken beta-actin (Cba) promoter as an efficient combination for driving the expression of exogenous Tmc1 in inner hair cells in vivo. Exogenous Tmc1 or its closely related ortholog, Tmc2, were capable of restoring sensory transduction, auditory brainstem responses, and acoustic startle reflexes in otherwise deaf mice, suggesting that gene augmentation with Tmc1 or Tmc2 is well suited for further development as a strategy for restoration of auditory function in deaf patients who carry TMC1 mutations. PMID- 26157031 TI - The proinflammatory role of HECTD2 in innate immunity and experimental lung injury. AB - Invading pathogens may trigger overactivation of the innate immune system, which results in the release of large amounts of proinflammatory cytokines (cytokine storm) and leads to the development of pulmonary edema, multiorgan failure, and shock. PIAS1 is a multifunctional and potent anti-inflammatory protein that negatively regulates several key inflammatory pathways such as Janus kinase (JAK) signal transducer and activator of transcription (STAT) and nuclear factor kappaB (NF-kappaB). We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. We found that GSK3beta phosphorylation of PIAS1 provided a phosphodegron for HECTD2 targeting. We also identified a mislocalized HECTD2 polymorphism, HECTD2(A19P), that was present in 8.5% of the population and functioned to reduce inflammation. This polymorphism prevented HECTD2/PIAS1 nuclear interaction, thus preventing PIAS1 degradation. The HECTD2(A19P) polymorphism was also protective toward acute respiratory distress syndrome (ARDS). We then developed a small-molecule inhibitor, BC-1382, that targeted HECTD2 and attenuated lipopolysaccharide (LPS)- and Pseudomonas aeruginosa induced lung inflammation. These studies describe an unreported innate immune pathway and suggest that mutation or antagonism of the E3 ligase HECTD2 results in reduced severity of lung inflammation by selectively modulating the abundance of the anti-inflammatory protein PIAS1. PMID- 26157032 TI - Absence of sperm RNA elements correlates with idiopathic male infertility. AB - Semen parameters are typically used to diagnose male infertility and specify clinical interventions. In idiopathic infertile couples, an unknown male factor could be the cause of infertility even when the semen parameters are normal. Next generation sequencing of spermatozoal RNAs can provide an objective measure of the paternal contribution and may help guide the care of these couples. We assessed spermatozoal RNAs from 96 couples presenting with idiopathic infertility and identified the final reproductive outcome and sperm RNA elements (SREs) reflective of fecundity status. The absence of required SREs reduced the probability of achieving live birth by timed intercourse or intrauterine insemination from 73 to 27%. However, the absence of these same SREs does not appear to be critical when using assisted reproductive technologies such as in vitro fertilization with or without intracytoplasmic sperm injection. About 30% of the idiopathic infertile couples presented an incomplete set of required SREs, suggesting a male component as the cause of their infertility. Conversely, analysis of couples that failed to achieve a live birth despite presenting with a complete set of SREs suggested that a female factor may have been involved, and this was confirmed by their diagnosis. The data in this study suggest that SRE analysis has the potential to predict the individual success rate of different fertility treatments and reduce the time to achieve live birth. PMID- 26157036 TI - Detection of Mild and Reversible Neurohistopathological Changes in the Brain of Juvenile (Preweaned) Beagle Dogs Treated with Vigabatrin for up to 91 Days. AB - Neurohistopathological changes in the brain were assessed in juvenile beagle dogs given vigabatrin at 30 or 100 mg/kg/day by oral gavage from postnatal day 22 (PND22) until 16 weeks of age (PND112), when brain myelination is considered to reach the adult stage in dogs. Separate subgroups were treated from PND22 to PND35 or PND36 to PND49 to assess early effects. In addition to extensive brain histopathology, there were assessments of toxicokinetics, clinical condition, body weight, organ weights, and macroscopic pathology. In animals treated for 14 days from PND22, minimal or slight vacuolation was seen in the neuropil of the septal nuclei, hippocampus, hypothalamus, thalamus, cerebellum, and globus pallidus at 100 mg/kg/day and minimal vacuolation in the thalamus, globus pallidus, and cerebellum at 30 mg/kg/day. In animals given 100 mg/kg/day for 91 days from PND22, minimal or slight vacuolation was observed only in the hippocampus, hypothalamus, and thalamus. No vigabatrin-related brain vacuolation was observed in animals given 30 or 100 mg/kg/day for 14 days from PND36. Clear evidence of recovery was observed after 14-day and 6-week off-dose periods that followed treatment from PND22 to PND35 or PND22 to PND112, respectively. PMID- 26157037 TI - Hormone Receptor Expression in Spontaneous Uterine Adenocarcinoma in Fischer 344 Rats. AB - Most uterine cancers, the most common gynecological malignancies in women in developed countries, are hormone-dependent endometrial adenocarcinomas (EACs) that express estrogen and progesterone receptors. Although rat strains exist with a high spontaneous incidence of EAC, the Fischer 344 (F344) strain, previously one of the most commonly used strains in carcinogenicity testing, is not a high incidence strain. To better understand the biology of this neoplasm, we assessed estrogen receptor alpha (ER), progesterone receptor (PR), and Ki-67 expression using immunohistochemistry in spontaneous EAC in 18 F344 rats used as control animals in 2-year National Toxicology Program bioassays. Of the 18 tumors, 9 were well-differentiated and 9 were poorly differentiated. Most tumors, 7/18, were ER+PR+, as observed in women. Of the remainder, 6/18 were ER+PR-, 2/18 were ER PR+, and 3/18 were ER-PR-. Well-differentiated tumors were ER+ (8/9) more often than poorly differentiated tumors (5/9). The percentage of ER+ tumors (72%) in rats was similar to that seen in women, but rats less frequently had PR+ (50%) tumors than women. The heterogeneous estrogen and progesterone receptor immunophenotypes observed in F344 rats in this study highlight the importance of evaluating hormone receptor expression in animal models used for chemical evaluations. PMID- 26157035 TI - A homozygous mutation of VWA3B causes cerebellar ataxia with intellectual disability. AB - BACKGROUND: Hereditary cerebellar ataxia constitutes a heterogeneous group of neurodegenerative disorders, occasionally accompanied by other neurological features. Genetic defects remain to be elucidated in approximately 40% of hereditary cerebellar ataxia cases in Japan. We attempted to identify the gene responsible for autosomal recessive cerebellar ataxia with intellectual disability. METHODS: The present study involved three patients in a consanguineous Japanese family. Neurological examination and gene analyses were performed in all family members. We performed genome-wide linkage analysis including single nucleotide polymorphism arrays, copy-number variation analysis and whole exome sequencing. To clarify the functional alteration resulting from the identified mutation, we performed cell viability assay of cultured cells expressing mutant protein. RESULTS: One homozygous region shared among the three patients on chromosomes 2p16.1-2q12.3 was identified. Using whole exome sequencing, six homozygous variants in genes in the region were detected. Only one variant, VWA3B c.A1865C, results in a change of a highly conserved amino acid (p.K622T) and was not present in control samples. VWA3B encodes a von Willebrand Factor A Domain-Containing Protein 3B with ubiquitous expression, including the cerebellum. The viability of cultured cells expressing the specific K622T mutation was proved to decrease through the activation of apoptotic pathway. CONCLUSIONS: Mutated VWA3B was found to be likely associated with cerebellar degeneration with intellectual disability. Although a rare cause of cerebellar degeneration, these findings indicate a critical role for VWA3B in the apoptosis pathway in neuronal tissues. PMID- 26157034 TI - Computational Psychiatry: towards a mathematically informed understanding of mental illness. AB - Computational Psychiatry aims to describe the relationship between the brain's neurobiology, its environment and mental symptoms in computational terms. In so doing, it may improve psychiatric classification and the diagnosis and treatment of mental illness. It can unite many levels of description in a mechanistic and rigorous fashion, while avoiding biological reductionism and artificial categorisation. We describe how computational models of cognition can infer the current state of the environment and weigh up future actions, and how these models provide new perspectives on two example disorders, depression and schizophrenia. Reinforcement learning describes how the brain can choose and value courses of actions according to their long-term future value. Some depressive symptoms may result from aberrant valuations, which could arise from prior beliefs about the loss of agency ('helplessness'), or from an inability to inhibit the mental exploration of aversive events. Predictive coding explains how the brain might perform Bayesian inference about the state of its environment by combining sensory data with prior beliefs, each weighted according to their certainty (or precision). Several cortical abnormalities in schizophrenia might reduce precision at higher levels of the inferential hierarchy, biasing inference towards sensory data and away from prior beliefs. We discuss whether striatal hyperdopaminergia might have an adaptive function in this context, and also how reinforcement learning and incentive salience models may shed light on the disorder. Finally, we review some of Computational Psychiatry's applications to neurological disorders, such as Parkinson's disease, and some pitfalls to avoid when applying its methods. PMID- 26157038 TI - Introduction of Zinc-salt Fixation for Effective Detection of Immune Cell-related Markers by Immunohistochemistry. AB - Tissue localization of immune cells is critical to the study of disease processes in mouse models of human diseases. However, immunohistochemistry (IHC) for immune cell phenotyping in mouse tissue sections presents specific technical challenges. For example, CD4 and CD8 have been difficult to detect using IHC on formalin fixed and paraffin-embedded mouse tissue, prompting alternative methods. We investigated the use of formalin-free zinc-salt fixation (ZN) and optimized IHC protocols for detecting a panel of immune cell-related markers (CD3, CD4, CD8, Foxp3, B220, F4/80, CD68, and major histocompatibility complex [MHC] class-I, MHC class-II, and Gr-1). The IHC results for these markers were compared on mouse spleen tissue treated with neutral buffered formalin (NBF) or ZN with or ZN without antigen retrieval (AR). Whereas CD4 and CD8 were not detected in NBF treated tissue, all markers were detected in ZN-treated tissue without AR. Thus, the use of ZN treatment for IHC staining can be a good tool for studying immunoreactive lesions in tissues. PMID- 26157039 TI - Doppler Tissue Evaluation of Atrial Conduction Properties in Patients With Non alcoholic Fatty-liver Disease. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in clinical practice, and there is an increasing trend in its prevalence in the general population. Recent studies have demonstrated increased risk of atrial fibrillation (AF) in NAFLD. However, information on the mechanism of increased risk of AF in NAFLD is lacking. Impaired atrial conduction is an important factor in the pathophysiology of AF. We aimed to investigate atrial conduction properties in patients with NAFLD by tissue Doppler echocardiography. Fifty-nine ultrasound diagnosed NAFLD patients without clinical diagnosis of hypertension, diabetes mellitus, or cardiac disease and 22 normal subjects as controls were included in this study. Atrial conduction properties were assessed by electromechanical delay (EMD) derived from Doppler tissue echocardiography examination and P-wave dispersion (PWD) calculated from the 12-lead electrocardiogram. Inter-atrial and intra-atrial EMD intervals were significantly longer in NAFLD patients than in controls (inter-atrial EMD, 31.9 +/- 8.5 ms vs. 23.4 +/- 4.6 ms,p= 0.0001, and intra-atrial EMD, 14.3 +/- 5.2 vs. 10.2 +/- 4.0 ms,p= 0.001). Similarly, PWD was significantly higher in NAFLD patients compared with controls (49.2 +/- 6.3 ms vs. 43.3 +/- 4.2 ms,p= 0.0001). Maximum left atrial volume was also significantly higher in the NAFLD group than in controls (51 +/- 11 mL vs. 34 +/- 9 mL,p< 0.0001). This study demonstrated that atrial conduction is impaired in patients with NAFLD. Also, in a patient population of NAFLD without any clinical diagnosis of cardiac disease, diabetes, or hypertension, left atrial volume was increased compared with controls. These findings suggest impaired atrial conduction as a factor in increased risk of AF in NAFLD. PMID- 26157040 TI - Effectiveness of a Pregnancy Smoking Intervention: The Tennessee Intervention for Pregnant Smokers Program. AB - Despite the known dangers of pregnancy smoking, rates remain high, especially in the rural, Southern United States. Interventions are effective, but few have been developed and tested in regions with high rates of pregnancy smoking, a culture that normalizes smoking, and a hard-to-reach prenatal population. The goals were to describe a smoking cessation intervention, the Tennessee Intervention for Pregnant Smokers program, and examine the impact on quit rates compared to usual care. Additionally we sought to examine reduction in smoking levels and number of quit attempts related to the intervention and finally to examine the impact of the intervention on birth outcomes. Intervention and historical control group participants, all smokers at entry to prenatal care, were recruited from five medical practices providing prenatal care in rural, South-Central Appalachia. The intervention, an expanded 5A's (Ask, Advise, Assess, Assist, Arrange) model, was delivered by trained health educators. Over 28% of intervention group women quit smoking, compared to 9.8% in the control group. Two thirds of intervention group women significantly reduced smoking by delivery, with 40%+ attempting to quit at least once. Compared to controls, intervention group women saw significantly better birth outcomes, including newborns weighing 270g more and 50% less likely to have a neonatal intensive care unit admission. Among intervention group participants, those who quit smoking had significantly better birth outcomes than those who did not quit smoking. Findings point to the potential for appropriately tailored pregnancy smoking interventions to produce substantial improvements in birth outcomes within populations with health disparities. PMID- 26157041 TI - A Process Evaluation of the Alaska Native Colorectal Cancer Family Outreach Program. AB - This article presents the results of a process evaluation of the Alaska Native (AN) Colorectal Cancer (CRC) Family Outreach Program, which encourages CRC screening among AN first-degree relatives (i.e., parents, siblings, adult children; hereafter referred to as relatives) of CRC patients. Among AN people incidence and death rates from CRC are the highest of any ethnic/racial group in the United States. Relatives of CRC patients are at increased risk; however, CRC can be prevented and detected early through screening. The evaluation included key informant interviews (August to November 2012) with AN and non-AN stakeholders and program document review. Five key process evaluation components were identified: program formation, evolution, outreach responses, strengths, and barriers and challenges. Key themes included an incremental approach that led to a fully formed program and the need for dedicated, culturally competent patient navigation. Challenges included differing relatives' responses to screening outreach, health system data access and coordination, and the program impact of reliance on grant funding. This program evaluation indicated a need for more research into motivating patient screening behaviors, electronic medical records systems quality improvement projects, improved data-sharing protocols, and program sustainability planning to continue the dedicated efforts to promote screening in this increased risk population. PMID- 26157042 TI - Long-Term Refugee Health: Health Behaviors and Outcomes of Cambodian Refugee and Immigrant Women. AB - Refugees in the United States have high rates of chronic disease. Both long-term effects of the refugee experience and adjustment to the U.S. health environment may contribute. While there is significant research on health outcomes of newly resettled refugees and long-term mental health experiences of established refugees, there is currently little information about how the combined effects of the refugee experience and the U.S. health environment are related to health practices of refugees in the years and decades after resettlement. We examined cross-sectional survey data for Cambodian refugee and immigrant women 35 to 60 years old (n = 160) from an established refugee community in Lowell, Massachusetts, to examine the potential contributors to health behaviors and outcomes among refugees and immigrants postresettlement. In our representative sample, we found that smoking and betel nut use were very low (4% each). Fewer than 50% of respondents walked for at least 10 minutes on 2 or more days/week. Using World Health Organization standards for overweight/obese for Asians, 73% of respondents were overweight/obese and 56% were obese, indicating increased risk of chronic disease. Depression was also high in this sample (41%). In multivariate models, higher acculturation and age were associated with walking more often; lower education and higher acculturation were related to higher weight; and being divorced/separated or widowed and being older were related to higher risk of depression. The interrelated complex of characteristics, health behaviors, and health outcomes of refugees merits a multifaceted approach to health education and health promotion for long-term refugee health. PMID- 26157043 TI - Sildenafil Does Not Prevent Heart Hypertrophy and Fibrosis Induced by Cardiomyocyte Angiotensin II Type 1 Receptor Signaling. AB - Analyses of several mouse models imply that the phosphodiesterase 5 (PDE5) inhibitor sildenafil (SIL), via increasing cGMP, affords protection against angiotensin II (Ang II)-stimulated cardiac remodeling. However, it is unclear which cell types are involved in these beneficial effects, because Ang II may exert its adverse effects by modulating multiple renovascular and cardiac functions via Ang II type 1 receptors (AT1Rs). To test the hypothesis that SIL/cGMP inhibit cardiac stress provoked by amplified Ang II/AT1R directly in cardiomyocytes (CMs), we studied transgenic mice with CM-specific overexpression of the AT1R under the control of the alpha-myosin heavy chain promoter (alphaMHC AT1R(tg/+)). The extent of cardiac growth was assessed in the absence or presence of SIL and defined by referring changes in heart weight to body weight or tibia length. Hypertrophic marker genes, extracellular matrix-regulating factors, and expression patterns of fibrosis markers were examined in alphaMHC-AT1R(tg/+) ventricles (with or without SIL) and corroborated by investigating different components of the natriuretic peptide/PDE5/cGMP pathway as well as cardiac functions. cGMP levels in heart lysates and intact CMs were measured by competitive immunoassays and Forster resonance energy transfer. We found higher cardiac and CM cGMP levels and upregulation of the cGMP-dependent protein kinase type I with AT1R overexpression. However, even a prolonged SIL treatment regimen did not limit the progressive CM growth, fibrosis, or decline in cardiac functions in the alphaMHC-AT1R(tg/+) model, suggesting that SIL does not interfere with the pathogenic actions of amplified AT1R signaling in CMs. Hence, the cardiac/noncardiac cells involved in the cross-talk between SIL-sensitive PDE activity and Ang II/AT1R still need to be identified. PMID- 26157045 TI - Authors' Explanation of the Retraction. PMID- 26157044 TI - Activation of Mas Oncogene-Related G Protein-Coupled Receptors Inhibits Neurochemical Alterations in the Spinal Dorsal Horn and Dorsal Root Ganglia Associated with Inflammatory Pain in Rats. AB - Mas oncogene-related G protein-coupled receptor C (MrgC) is unequally expressed in sensory ganglia and has been shown to modulate pathologic pain. This study investigated the mechanism underlying the effect of MrgC receptors on inflammatory pain. Intrathecal administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) (30 nmol) inhibited complete Freund's adjuvant-evoked hyperalgesia. This was associated with the inhibition of protein kinase C-gamma and phosphorylated extracellular signal-regulated protein kinase in the spinal cord and/or dorsal root ganglia (DRG). The complete Freund's adjuvant injection in the hindpaw induced an increase in Gq, but not Gi and Gs, protein in the spinal dorsal horn. This increase was inhibited by the intrathecal administration of BAM8-22. The exposure of DRG cultures to bradykinin (10 MUM) and prostaglandin E2 (1 MUM) increased the expression of calcitonin gene-related peptide (CGRP) and neuronal nitric oxide synthase in small- and medium-sized neurons as well as the levels of CGRP, aspartate, and glutamate in the cultured medium. The bradykinin/prostaglandin E2-induced alterations were absent in the presence of BAM8-22 (10 nM). These results suggest that the activation of MrgC receptors can modulate the increase in the expression of CGRP and neuronal nitric oxide synthase as well as the release of CGRP and excitatory amino acids in DRG associated with inflammatory pain. This modulation results in the inhibition of pain hypersensitivity by suppressing the expression of Gq protein and protein kinase C-gamma and extracellular signal-regulated protein kinase signaling pathways in the spinal cord and/or DRG. The present study suggests that MrgC receptors may be a novel target for relieving inflammatory pain. PMID- 26157046 TI - Behavioral and Educational Interventions to Support Family Caregivers in End-of Life Care: A Systematic Review. AB - The demand for family caregivers steadily increases as the number of people receiving hospice and palliative care rises. Family caregivers play a significant role in supporting their loved ones in end-of-life care. However, there is limited evidence about the effectiveness of the interventions for supporting family caregivers. This article synthesizes behavioral and educational interventions that support family caregivers in end-of-life care. A systematic review was conducted and searched interventional studies published between 2004 and 2014 in PubMed, CINAHL, Embase, and The Cochrane Library electronic databases. Fourteen studies were identified and analyzed: 4 educational studies, 6 cognitive behavioral therapy studies, and 4 psychoeducational studies. All educational and behavioral interventions had developed structures and treatment manuals and improved family caregivers' outcomes. The cognitive behavioral therapy resulted in more positive outcomes than the other 2 interventions. More rigorous randomized controlled trials are needed to replicate current effective interventions with larger and diverse sample. Future studies need to develop tools for assessing family caregivers' needs, create consistent and specific tools to effectively measure family caregivers' outcomes, incorporate a cost effectiveness analysis, and find the most efficient intervention format and method. PMID- 26157047 TI - Galactomannan and Polymerase Chain Reaction-Based Screening for Invasive Aspergillosis Among High-Risk Hematology Patients: A Diagnostic Meta-analysis. AB - BACKGROUND: Screening of high-risk patients for invasive aspergillosis (IA) has the potential to decrease the use of empiric antifungal agents. However, the performance of different screening methods has not been studied. METHODS: We performed a meta-analysis of published studies to assess the diagnostic performance of galactomannan (GM) and polymerase chain reaction (PCR) as weekly screening tests in high-risk populations. The sensitivity and specificity of 6 approaches combining GM and PCR were estimated using the bivariate model. RESULTS: Thirteen studies with 1670 patients met our inclusion criteria. Single positive test results had modest sensitivity and specificity for screening (respectively, 92% and 90% for GM; 84% and 76% for PCR). The screening approach with the highest sensitivity was the one that used at least 1 GM- or PCR-positive result to define a positive episode, achieving a sensitivity of 99%, significantly higher than any single test (P = .0018 compared with GM and P < .0001 compared with PCR). Meanwhile, when both GM and PCR were positive for the same patient, the specificity increased to 98%, which was not significantly different compared to the specificity of at least 2 positive GM (95%, P = .56 for the comparison) or PCR results (93%, P = .07 for the comparison). CONCLUSIONS: When screening high-risk patients for IA with GM and PCR tests, the absence of any positive test can obviate the need for antifungal agents with a negative predictive value of 100%, whereas the presence of at least 2 positive results is highly suggestive of an active infection with a positive predictive value of 88%. PMID- 26157048 TI - Regarding Primary Care Patients Who Received Influenza Vaccine at Veteran Health Administration Medical Centers. PMID- 26157049 TI - Rosuvastatin Worsens Insulin Resistance in HIV-Infected Adults on Antiretroviral Therapy. AB - BACKGROUND: Statins are associated with increased diabetes risk in large, human immunodeficiency virus (HIV)-uninfected cohorts; the impact of statins on insulin resistance or diabetes in HIV-infected persons has not been assessed within a randomized controlled study. METHODS: HIV-infected participants on stable antiretroviral therapy with a low-density lipoprotein cholesterol level of <=130 mg/dL and heightened immune activation or inflammation were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. Fasting serum glucose, insulin, and hemoglobin A1C (HgbA1C) were measured; insulin resistance was estimated by calculating the homeostatic model assessment of insulin resistance (HOMA-IR); and a 2-hour oral glucose tolerance test was administered. RESULTS: Seventy-two participants were randomized to rosuvastatin therapy and 75 to placebo. Increases in fasting glucose were observed within both groups but were not different between study arms (P = .115); changes in glucose tolerance and HgbA1C did not differ between study arms (P = .920 and P = .650, respectively). Criteria for diabetes were met by 1 participant in the rosuvastatin and 3 in the placebo arm by week 96. Compared with placebo, rosuvastatin therapy was associated with significantly greater increases in insulin and HOMA-IR (P = .008 and P = .004, respectively). CONCLUSIONS: We detected a significant worsening in insulin resistance and an increase in the proportion of participants with impaired fasting glucose but not a clinical diagnosis of diabetes in the rosuvastatin arm. Our findings suggest that prescription of statin therapy should be accompanied by a careful consideration of the risks and benefits, particularly in patients with lower cardiovascular disease risk. CLINICAL TRIALS REGISTRATION: NCT01218802. PMID- 26157051 TI - Reply to Decker et al. PMID- 26157050 TI - Long-term Virological Outcomes of First-Line Antiretroviral Therapy for HIV-1 in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis. AB - BACKGROUND: More than 11.7 million people are currently receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs), and focused efforts are needed to ensure high levels of adherence and to minimize treatment failure. Recently, international targets have emphasized the importance of long-term virological suppression as a key measure of program performance. METHODS: We systematically reviewed publications and conference abstracts published between January 2006 and May 2013 that reported virological outcomes among human immunodeficiency virus type 1 (HIV-1)-infected adults receiving first-line ART for up to 5 years in LMICs. Summary estimates of virological suppression after 6, 12, 24, 36, 48, and 60 months of ART were analyzed using random-effects meta analysis. Intention-to-treat (ITT) analysis assumed all participants who were lost to follow-up, died, or stopped ART as having virological failure. RESULTS: Summary estimates of virological suppression remained >80% for up to 60 months of ART for all 184 included cohorts. ITT analysis yielded 74.7% (95% confidence interval [CI], 72.2-77.2) suppression after 6 months and 61.8% (95% CI, 44.0 79.7) suppression after 48 months on ART. Switches to second-line ART were reported scarcely. CONCLUSIONS: Among individuals retained on ART, virological suppression rates during the first 5 years of ART were high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years. PMID- 26157052 TI - Dermatomyositis presenting as a paraneoplastic syndrome with resolution of symptoms following surgical management of underlying breast malignancy. AB - Breast cancer is the most common cancer in women in the USA, with the lifetime incidence of 1 in 8 women. Dermatomyositis (DM) is an uncommon idiopathic inflammatory myopathy that can manifest as a paraneoplastic syndrome of an underlying malignancy. Here, we report a case of a patient who presented with breast cancer and DM symptoms. The patient's rash and muscle weakness progressed during the workup of her breast cancer, while she was already started on medical treatment of these symptoms with oral prednisone. Her cutaneous and musculoskeletal improved dramatically following the treatment of her breast cancer. Our case report describes the rapid progression and regression of her symptoms emphasizing the benefit of early diagnosis and treatment of DM as well as the underlying breast cancer. PMID- 26157053 TI - Laparo-endoscopic combined approach for excision of gastrointestinal stromal tumour close to the oesophagogastric junction. AB - Tumours close to the oesophagogastric junction (OGJ) are difficult to excise due to high risk of complications. Laparoscopic and endoscopic combined surgery allows minimally invasive access while increasing tumour visualization. Computed tomography (CT) scanning of a 68-year-old female demonstrated a lesion suspicious of a gastrointestinal stromal tumour located 2 cm from the OGJ on the posterior gastric wall. Stapled excision was performed intragastrically and followed by endoscopic removal. Gastroscopy 7 months post-op and follow-up CT scan at 5 years demonstrated no recurrence of the primary tumour and no new disease. Laparoscopic and endoscopic combined approach is a safe and effective method of removing tumours close to the OGJ. PMID- 26157054 TI - Combined facial heating and inhalation of hot air do not alter thermoeffector responses in humans. AB - The influence of thermoreceptors in human facial skin on thermoeffector responses is equivocal; furthermore, the presence of thermoreceptors in the respiratory tract and their involvement in thermal homeostasis has not been elucidated. This study tested the hypothesis that hot air directed on the face and inhaled during whole body passive heat stress elicits an earlier onset and greater sensitivity of cutaneous vasodilation and sweating than that directed on an equal skin surface area away from the face. Six men and two women completed two trials separated by ~1 wk. Participants were passively heated (water-perfused suit; core temperature increase ~0.9 degrees C) while hot air was directed on either the face or on the lower leg (counterbalanced). Skin blood flux (laser-Doppler flowmetry) and local sweat rate (capacitance hygrometry) were measured at the chest and one forearm. During hot-air heating, local temperatures of the cheek and leg were 38.4 +/- 0.8 degrees C and 38.8 +/- 0.6 degrees C, respectively (P = 0.18). Breathing hot air combined with facial heating did not affect mean body temperature onsets (P = 0.97 and 0.27 for arm and chest sites, respectively) or slopes of cutaneous vasodilation (P = 0.49 and 0.43 for arm and chest sites, respectively), or the onsets (P = 0.89 and 0.94 for arm and chest sites, respectively), or slopes of sweating (P = 0.48 and 0.65 for arm and chest sites, respectively). Based on these findings, respiratory tract thermoreceptors, if present in humans, and selective facial skin heating do not modulate thermoeffector responses during passive heat stress. PMID- 26157055 TI - Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3 independent taste transduction pathway in mice. AB - Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. PMID- 26157056 TI - N-methyl-d-aspartate receptor coagonist d-serine suppresses intake of high preference food. AB - d-Serine is abundant in the forebrain and physiologically important for modulating excitatory glutamatergic neurotransmission as a coagonist of synaptic N-methyl-d-aspartate (NMDA) receptor. NMDA signaling has been implicated in the control of food intake. However, the role of d-serine on appetite regulation is unknown. To clarify the effects of d-serine on appetite, we investigated the effect of oral d-serine ingestion on food intake in three different feeding paradigms (one-food access, two-food choice, and refeeding after 24-h fasting) using three different strains of male mice (C57Bl/6J, BKS, and ICR). The effect of d-serine was also tested in leptin signaling-deficient db/db mice and sensory deafferented (capsaicin-treated) mice. The expression of orexigenic neuropeptides [neuropeptide Y (Npy) and agouti-related protein (Agrp)] in the hypothalamus was compared in fast/refed experiments. Conditioned taste aversion for high-fat diet (HFD) was tested in the d-serine-treated mice. Under the one-food-access paradigm, some of the d-serine-treated mice showed starvation, but not when fed normal chow. HFD feeding with d-serine ingestion did not cause aversion. Under the two-food-choice paradigm, d-serine suppressed the intake of high-preference food but not normal chow. d-Serine also effectively suppressed HFD intake but not normal chow in db/db mice and sensory-deafferented mice. In addition, d-serine suppressed normal chow intake after 24-h fasting despite higher orexigenic gene expression in the hypothalamus. d-Serine failed to suppress HFD intake in the presence of L-701,324, the selective and full antagonist at the glycine-binding site of the NMDA receptor. Therefore, d-serine suppresses the intake of high preference food through coagonism toward NMDA receptors. PMID- 26157057 TI - Reviving the use of aldosterone inhibitors in treating hypertension in obesity. AB - Obesity is a multifactorial disease associated with hypertension. In the obese population, the incidence of hypertension is high and resistant hypertension is commonly observed. Mechanisms to explain the resistance to current antihypertensive treatments are still poorly understood. Emerging knowledge of the role of aldosterone in controlling blood pressure in obesity may have therapeutic benefit. Mineralocorticoid receptor (MR) inhibitors are currently used as the fourth line of treatment. Clinical studies summarized in this short review suggest that MR antagonists have a strong efficacy in decreasing blood pressure in the hypertensive obese population and could be used as a primary antihypertensive in obesity. PMID- 26157058 TI - Somatostatin receptor activation is involved in the control of daily torpor in a seasonal mammal. AB - Siberian hamsters (Phodopus sungorus) show spontaneous daily torpor only after ~2 mo in winter-like short photoperiods (SP). Although some SP-induced hormonal changes have been demonstrated to be necessary for the occurrence of seasonal torpor, the whole set of preconditions is still unknown. Recent findings provide evidence that the hypothalamic pituitary growth axis is involved in endocrine responses to SP exposure in the photoperiodic hamsters. To examine whether suppression of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion affects the incidence of daily torpor, we used two somatostatin receptor agonists, pasireotide (SOM230) and octreotide, with different affinity profiles for receptor subtypes. Pasireotide strikingly increased the torpor frequency in male hamsters compared with sham-treated controls, and torpor duration was often increased, which in some cases exceeded 12 h. In contrast, administration of octreotide reduced the body weight of SP hamsters but had only a marginal effect on torpor frequency in males and no effect in females. Together with measured concentrations of circulating IGF-1, the present results strongly suggest that reduced activity of the GH/IGF-1 axis is not critical for stimulation of torpor expression but activation of specific somatostatin receptors is critical. This putative role for certain somatostatin receptor subtypes in torpor induction provides a promising new approach to unravel the endocrine mechanisms of torpor regulation. PMID- 26157059 TI - Aerobic exercise training reduces cardiac function in adult male offspring exposed to prenatal hypoxia. AB - Intrauterine growth restriction (IUGR) has been associated with increased susceptibility to myocardial ischemia-reperfusion (I/R) injury. Exercise is an effective preventive intervention for cardiovascular diseases; however, it may be detrimental in conditions of compromised health. The aim of this study was to determine whether exercise training can improve cardiac performance after I/R injury in IUGR offspring. We used a hypoxia-induced IUGR model by exposing pregnant Sprague-Dawley rats to 21% oxygen (control) or hypoxic (11% oxygen; IUGR) conditions from gestational day 15 to 21. At 10 wk of age, offspring were randomized to a sedentary group or to a 6-wk exercise protocol. Transthoracic echocardiography assessments were performed after 6 wk. Twenty-four hours after the last bout of exercise, ex vivo cardiac function was determined using a working heart preparation. With exercise training, there was improved baseline cardiac performance in male control offspring but a reduced baseline cardiac performance in male IUGR exercised offspring (P < 0.05). In male offspring, exercise decreased superoxide generation in control offspring, while in IUGR offspring, it had the polar opposite effect (interaction P <= 0.05). There was no effect of IUGR or exercise on cardiac function in female offspring. In conclusion, in male IUGR offspring, exercise may be a secondary stressor on cardiac function. A reduction in cardiac performance along with an increase in superoxide production in response to exercise was observed in this susceptible group. PMID- 26157060 TI - Technical recommendations for the use of carotid duplex ultrasound for the assessment of extracranial blood flow. AB - Duplex ultrasound is an evolving technology that allows the assessment of volumetric blood flow in the carotid and vertebral arteries during a range of interventions along the spectrum of health and chronic disease. Duplex ultrasound can provide high-resolution diameter and velocity information in real-time and is noninvasive with minimal risks or contraindications. However, this ultrasound approach is a specialized technique requiring intensive training and stringent control of multiple complex settings; results are highly operator-dependent, and analysis approaches are inconsistent. Importantly, therefore, methodological differences can invalidate comparisons between different imaging modalities and studies; such methodological errors have potential to discredit study findings completely. The task of this review is to provide the first comprehensive, user friendly technical guideline for the application of duplex ultrasound in measuring extracranial blood flow in human research. An update on recent developments in the use of edge-detection software for offline analysis is highlighted, and suggestions for future directions in this field are provided. These recommendations are presented in an attempt to standardize measurements across research groups and, hence, ultimately to improve the accuracy and reproducibility of measuring extracranial blood flow both within subjects and between groups. PMID- 26157061 TI - Exploring the OVLT: insight into a critically important window into the brain. PMID- 26157063 TI - A Missed Opportunity to Improve Patient Satisfaction? Patient Perceptions of Inpatient Communication With Their Primary Care Physician. AB - Improving patient satisfaction is a major focus of hospitals. Patient satisfaction could be driven by patient perception of hospital team communication with their primary care physician (PCP). A retrospective mixed methods approach was used to characterize the relationship between patient satisfaction and patient perception of hospital team-PCP communication. Data were obtained through general medicine inpatient and postdischarge interviews, oversampling "vulnerable elders," and a faxed PCP survey. Among 1044 patients and their PCPs, 22.3% of PCPs were not aware of their patient's hospitalization. Among PCPs who reported that communication did not occur, half (49.2%) of their patients thought communication had occurred, implying a lack of patient awareness of discontinuity of care and possibly impeding safety. Patients who perceived that communication occurred were more satisfied with care (70.0% vs 53.1%, P < .001). Therefore, hospitals could potentially improve patient safety and satisfaction by seizing a missed opportunity to improve patient awareness of communication. PMID- 26157062 TI - Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia. AB - Brainstem catecholamine neurons modulate sensory information and participate in control of cardiorespiratory function. These neurons have multiple projections, including to the paraventricular nucleus (PVN), which contributes to cardiorespiratory and neuroendocrine responses to hypoxia. We have shown that PVN projecting catecholaminergic neurons are activated by hypoxia, but the function of these neurons is not known. To test the hypothesis that PVN-projecting catecholamine neurons participate in responses to respiratory challenges, we injected IgG saporin (control; n = 6) or anti-dopamine beta-hydroxylase saporin (DSAP; n = 6) into the PVN to retrogradely lesion catecholamine neurons projecting to the PVN. After 2 wk, respiratory measurements (plethysmography) were made in awake rats during normoxia, increasing intensities of hypoxia (12, 10, and 8% O2) and hypercapnia (5% CO2-95% O2). DSAP decreased the number of tyrosine hydroxylase-immunoreactive terminals in PVN and cells counted in ventrolateral medulla (VLM; -37%) and nucleus tractus solitarii (nTS; -36%). DSAP produced a small but significant decrease in respiratory rate at baseline (during normoxia) and at all intensities of hypoxia. Tidal volume and minute ventilation (VE) index also were impaired at higher hypoxic intensities (10-8% O2; e.g., VE at 8% O2: IgG = 181 +/- 22, DSAP = 91 +/- 4 arbitrary units). Depressed ventilation in DSAP rats was associated with significantly lower arterial O2 saturation at all hypoxic intensities. PVN DSAP also reduced ventilatory responses to 5% CO2 (VE: IgG = 176 +/- 21 and DSAP = 84 +/- 5 arbitrary units). Data indicate that catecholamine neurons projecting to the PVN are important for peripheral and central chemoreflex respiratory responses and for maintenance of arterial oxygen levels during hypoxic stimuli. PMID- 26157064 TI - Skin prick test results to artesunate in children sensitized to Artemisia vulgaris L. AB - Artemisia vulgaris L and Artemisia annua L (Chinese: qinghao) are similar plants of the Asterbaceae family. Artesunate, a semi-synthetic derivate of artemisin which is the active principle extract of the plant qinghao, has antimalarial properties. Some cases of severe allergic reactions to artesunate have been described. The purpose of this study was to evaluate the association between positive skin tests to Artemisia vulgaris L allergen and a preparation of injectable artesunate. A total of 531 children were skin prick tested with inhalants (including Artemisia vulgaris L), foods, and artesunate. Among the 59 patients positive to Artemisia vulgaris L only one child was also positive to artesunate. No child was positive to artesunate in those negative to Artemisia vulgaris L. We conclude that Artemisia vulgaris L sensitization is not associated with sensitization to artesunate; consequently, skin test to artesunate should not be carried out before using the drug considering the rare allergic reactions. PMID- 26157065 TI - Inhibitory effects of Chikusetsusaponin IVa on lipopolysaccharide-induced pro inflammatory responses in THP-1 cells. AB - This study investigated anti-inflammatory effects and possible mechanisms of Chikusetsusaponin IVa (Chi IVa), one of the main bioactive components in saponins from Panacis japonica (SPJ), which is used in traditional Tujia and Hmong Chinese medicine. To this end, changes in the inflammatory profiles of lipopolysacchride (LPS)-stimulated phrobol 12-myristate 13-acetate(PMA)-differented THP-1 macrophages were evaluated following Chi IVa treatment. The results showed that Chi IVa markedly decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) at both the mRNA and protein level, which proved to be dose-dependent. Further studies revealed that Chi IVa strongly suppressed NF-kappaB activation and downregulated the phosphorylation of ERK, p38, and JNK. Our present study demonstrates that Chi IVa suppresses the production of iNOS, COX-2, IL-1beta, IL-6, and TNF-alpha in LPS-stimulated THP-1 cells likely by inhibiting NF-kappaB activation and ERK, JNK, and p38 signal pathway phosphorylation. PMID- 26157066 TI - TLR4 Signaling Is a Major Mediator of the Female Tract Response to Seminal Fluid in Mice. AB - Seminal fluid interacts with epithelial cells lining the female reproductive tract to induce expression of proinflammatory cytokines and chemokines, initiating immune tolerance mechanisms to facilitate pregnancy. TGFB cytokines are key signaling agents in seminal plasma but do not fully account for the female response to seminal fluid. We hypothesized that additional molecular pathways are utilized in seminal fluid signaling. Affymetrix microarray was employed to compare gene expression in the endometrium of mice 8 h after mating with either intact males or seminal fluid deficient (SVX/VAS) males. Bioinformatics analysis revealed TLR4 signaling as a strongly predicted upstream regulator activated by the differentially expressed genes and implicated TGFB signaling as a second key pathway. Quantitative PCR and microbead data confirmed that seminal fluid induces endometrial synthesis of several TLR4-regulated cytokines and chemokines, including CSF3, CXCL1, CXCL2, IL1A, IL6, LIF, and TNF. In primary uterine epithelial cells, CSF3, CXCL1, and CXCL2 were strongly induced by the TLR4 ligand LPS but suppressed by TGFB, while IL1A, TNF, and CSF2 were induced by both ligands. TLR4 was confirmed as essential for the full endometrial cytokine response using mice with a null mutation in Tlr4, where seminal fluid failed to induce endometrial Csf3, Cxcl2, Il6, and Tnf expression. This study provides evidence that TLR4 contributes to seminal fluid modulation of the periconception immune environment. Activation of TLR4 signaling by microbial or endogenous components of seminal fluid is thus implicated as a key element of the female tract response to seminal fluid at the outset of pregnancy in mice. PMID- 26157067 TI - Maternal High-Fat Diet Causes a Sex-Dependent Increase in AGTR2 Expression and Cardiac Dysfunction in Adult Male Rat Offspring. AB - Maternal high-fat diet (HFD) is associated with cardiovascular disease later in life. This study tested the hypothesis that maternal HFD causes programming of increased cardiac angiotensin II receptor type 2 (AGTR2) expression, resulting in heightened cardiac susceptibility to ischemic injury in male offspring in a sex dependent manner. Pregnant rats were divided between control and HFD (HFD-fed during gestation) groups. Maternal HFD resulted in cardiac hypertrophy in only male offspring, but had no effect on cardiac systolic and diastolic function in both male and female offspring. In addition, maternal HFD increased heart susceptibility to ischemia-reperfusion injury in adult male offspring, but not female offspring. There was an increase in Agtr2 mRNA and protein abundance in male, but not female offspring. However, maternal HFD had no effect on angiotensin II receptor type 1 (AGTR1) expression in both male and female offspring. HFD resulted in decreased glucocorticoid receptors (GRs) binding to the glucocorticoid response elements at the Agtr2 promoter, which was due to decreased GRs in the hearts of adult male offspring. Inhibition of AGTR2 with PD123319 abrogated maternal HFD-induced increase in cardiac ischemic vulnerability in male adult rats. The results demonstrate that maternal HFD causes programming of increased Agtr2 gene expression in the heart by downregulation of GR, contributing to the heightened cardiac vulnerability to ischemic injury in adult male offspring in a sex-dependent manner. PMID- 26157068 TI - Analysis of the Expression of Tachykinins and Tachykinin Receptors in the Rat Uterus During Early Pregnancy. AB - The peptides of the tachykinin family participate in the regulation of reproductive function acting at both central and peripheral levels. Our previous data showed that treatment of rats with a tachykinin NK3R antagonist caused a reduction of litter size. In the present study, we analyzed the expression of tachykinins and tachykinin receptors in the rat uterus during early pregnancy. Uterine samples were obtained from early pregnant rats (Days 1-9 of pregnancy) and from nonpregnant rats during the proestrus stage of the ovarian cycle, and real-time quantitative RT-PCR, immunohistochemistry, and Western blot studies were used to investigate the pattern of expression of tachykinins and tachykinin receptors. We found that all tachykinins and tachykinin receptors were locally synthesized in the uterus of early pregnant rats. The expression of substance P, neurokinin B, and the tachykinin receptors NK1R and NK3R mRNAs and proteins underwent major changes during the days around implantation and they were widely distributed in implantation sites, being particularly abundant in decidual cells. These findings support the involvement of the tachykinin system in the series of uterine events that occur around embryo implantation in the rat. PMID- 26157070 TI - Sperm Factors and Oocyte Activation: Current Controversies and Considerations. AB - The beginning of embryogenesis is preceded by a sequence of events mediated by the release of intracellular calcium in the ooplasm, a multifaceted process known as oocyte activation. It is now well established that a sperm protein factor introduced into the oocyte at the time of gamete fusion is responsible for initiating the cascade of signaling events involved. Several sperm proteins have been hypothesized as the sperm oocyte-activating factor (SOAF) over the years, with phospholipase C zeta 1 (PLCZ1 or PLCzeta) emerging as the strongest candidate. A large body of consistent and reproducible evidence, from both biochemical and clinical settings, has accumulated in support of PLCzeta, and data clearly demonstrate that oocyte activation ability can be rescued in PLCzeta deficient sperm by either PLCzeta cRNA or recombinant PLCzeta protein. However, a series of recent publications has challenged the dominance of PLCzeta and proposed an alternative candidate protein, WBP2 N-terminal like (WBP2NL or PAWP). These events have led to significant debate, fueled by the opposing views of two independent laboratories, each defending its own respective SOAF candidate. This raises important questions with regards to the relative importance of these two proteins in diagnostic and therapeutic medicine, and invites urgent research attention. Here, it is our intention to reflect upon this now very controversial area in order to engage the scientific and clinical communities in addressing the true importance of these two sperm proteins. PMID- 26157069 TI - Serotonin reuptake inhibitor citalopram inhibits GnRH synthesis and spermatogenesis in the male zebrafish. AB - Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants for the treatment of depression. However, SSRIs cause sexual side effects such as anorgasmia, erectile dysfunction, and diminished libido that are thought to be mediated through the serotonin (5-hydroxytryptamine, 5-HT) system. In vertebrates, gonadotropin-releasing hormone (GnRH) neurons play an important role in the control of reproduction. To elucidate the neuroendocrine mechanisms of SSRI-induced reproductive failure, we examined the neuronal association between 5 HT and GnRH (GnRH2 and GnRH3) systems in the male zebrafish. Double-label immunofluorescence and confocal laser microscopy followed by three-dimensional construction analysis showed close associations between 5-HT fibers with GnRH3 fibers and preoptic-GnRH3 cell bodies, but there was no association with GnRH2 cell bodies and fibers. Quantitative real-time PCR showed that short-term treatment (2 wk) with low to medium doses (4 and 40 MUg/L, respectively) of citalopram significantly decreased mRNA levels of gnrh3, gonadotropins (lhb and fshb) and 5-HT-related genes (tph2 and sert) in the male zebrafish. In addition, short-term citalopram treatment significantly decreased the fluorescence density of 5-HT and GnRH3 fibers compared with controls. Short-term treatment with low, medium, and high (100 MUg/L) citalopram doses had no effects on the profiles of different stages of spermatogenesis, while long-term (1 mo) citalopram treatment with medium and high doses significantly inhibited the different stages of spermatogenesis. These results show morphological and functional associations between the 5-HT and the hypophysiotropic GnHR3 system, which involve SSRI induced reproductive failures. PMID- 26157071 TI - The Family Secrets of Avian Egg-Specific Ovalbumin and Its Related Proteins Y and X. AB - The ovalbumin gene family in Gallus gallus is composed of three homologous genes located within a 46 kb locus on chromosome 2: ovalbumin, ovalbumin-related protein Y (OVAY), and ovalbumin-related protein X (OVAX) genes. The expression of these genes in hen oviduct is under estrogen control, but their relative hormonal responsiveness and subsequent protein concentration in egg, is distinctive. Interestingly, all three proteins lack the classical signal peptide for secretion. Ovalbumin, OVAX, and OVAY belong to the serine protease inhibitor (serpin) family whose members share a common tertiary structure. Ovalbumin and OVAX are one of the few members of this family that do not express any protease inhibition activity whereas OVAY has been predicted to be inhibitory, by comparison with the consensus sequence for inhibitory serpins. In contrast to ovalbumin and OVAY, OVAX interacts with heparin, a negatively charged glycosaminoglycan, via a positively charged domain exposed at the surface of the molecule. Ovalbumin is the major egg white protein and might be a source of amino acids for the developing embryo. The physiological function of OVAY is not known, but recent data have revealed a possible role of this protein in early embryonic development. Considering the antibacterial activities of OVAX, this protein might play a role in egg defense. This review sheds light on the expression, biochemistry, and structural specificities of these three highly similar paralogs. It gives new clues in favor of diverging functions, which are likely to have arisen by duplication events from a common ancestral gene. PMID- 26157072 TI - Performance of Rodent Spermatozoa Over Time Is Enhanced by Increased ATP Concentrations: The Role of Sperm Competition. AB - Sperm viability, acrosome integrity, motility, and swimming velocity are determinants of male fertility and exhibit an extreme degree of variation among closely related species. Many of these sperm parameters are associated with sperm ATP content, which has led to predictions of trade-offs between ATP content and sperm motility and velocity. Selective pressures imposed by sperm competition have been proposed as evolutionary causes of this pattern of diversity in sperm traits. Here, we examine variation in sperm viability, acrosome integrity, motility, swimming velocity, and ATP content over time, among 18 species of closely related muroid rodents, to address the following questions: (a) Do sperm from closely related species vary in ATP content after a period of incubation? (b) Are these differences in ATP levels related to differences in other sperm traits? (c) Are differences in ATP content and sperm performance over time explained by the levels of sperm competition in these species? Our results revealed a high degree of interspecific variability in changes in sperm ATP content, acrosome integrity, sperm motility and swimming velocity over time. Additionally, species with high sperm competition levels were able to maintain higher levels of sperm motility and faster sperm swimming velocity when they were incubated under conditions that support sperm survival. Furthermore, we show that the maintenance of such levels of sperm performance is correlated with the ability of sperm to sustain high concentrations of intracellular ATP over time. Thus, sperm competition may have an important role maximizing sperm metabolism and performance and, ultimately, the fertilizing capacity of spermatozoa. PMID- 26157073 TI - The Expression Pattern of MicroRNAs and the Associated Pathways Involved in the Development of Porcine Placental Folds That Contribute to the Expansion of the Exchange Surface Area. AB - The development of the microscopically folded structure of the diffuse epitheliochorial placenta in pigs is important because it expands the surface area for maternal-fetal exchange, resulting in an increase in placental efficiency. To better understand the regulatory mechanisms involved in this process, we characterized miRNA expression profiles in porcine placentas during the initiation and establishment of placental fold development. A total of 42 miRNAs were found to be differentially expressed, and their putative target genes were predicted using four target prediction programs. Following a comparative analysis with published gene expression pattern data obtained from porcine placentas in the corresponding stages of placental fold development, only those genes that were negatively correlated with miRNA expression were retained for further function and pathway enrichment analysis. The results showed that the up regulated miRNAs were associated mainly with extracellular matrix remodeling and tissue morphogenesis, while the down-regulated miRNAs were related to cell proliferation and signal transduction. Furthermore, we provide evidence that miR 130b may facilitate the expression of HPSE, which has been reported to be a regulator of the folding of the pig placenta, by suppressing the expression of PPARG. In addition, we also reveal that the miRNA-target pairs expressed in the pig placenta may trigger the degradation of the stromal matrix and basement membrane (miR-29a-COL1A2, COL3A1, and LAMC1) and regulate trophoblast epithelial cell adherens junctions (the miR-200 family and miR-205-ZEB2-CDH1) and proliferation (miR-17-92 cluster-HBP1 and ULK1). Taken together, these results indicate that miRNAs and related pathways may have potential roles in porcine placental fold development. PMID- 26157074 TI - Autoenucleation in the context of psychosis. PMID- 26157075 TI - Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. AB - Current management of hemophilia A includes prophylaxis with factor VIII (FVIII) replacement every 2 to 3 days. BAX 855, Baxalta's pegylated full-length recombinant FVIII (rFVIII), was designed to increase half-life and, thus, reduce the frequency of prophylactic infusions while maintaining hemostatic efficacy. BAX 855 was evaluated in previously treated patients with severe hemophilia A who were aged 12 to 65 years. A phase 1 study compared the pharmacokinetic (PK) profile of BAX 855 with that of licensed rFVIII (Advate). In a pivotal study, the annualized bleeding rate (ABR), PK parameters, and efficacy of bleeding treatment were assessed. In the phase 1 study, the mean half-life (T1/2) and the mean residence time of BAX 855 compared with Advate were 1.4- to 1.5-fold higher. These results were confirmed in the pivotal study. The pivotal study met its primary endpoint: Prophylaxis with BAX 855 resulted in an ABR that was significantly lower than half the ABR of on-demand treatment (P < .0001). The median ABR was 1.9, and 39.6% of compliant subjects had no bleeding episodes during prophylaxis, whereas subjects treated on-demand had a median ABR of 41.5. BAX 855 was also efficacious for the treatment of bleeding episodes, with 95.9% of bleeding episodes treated with 1 to 2 infusions and 96.1% having efficacy ratings of excellent/good. No FVIII inhibitory antibodies or safety signals were identified. These studies provide evidence that BAX 855 was safe and efficacious for on-demand treatment and prophylaxis administered twice weekly in patients with hemophilia A. The trials were registered at www.clinicaltrials.gov as #NCT01736475 and #NCT01599819. PMID- 26157076 TI - Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. AB - This phase 3 trial (Eastern Cooperative Oncology Group [ECOG] E1A06) compared melphalan, prednisone, and thalidomide (MPT-T) with melphalan, prednisone, and lenalidomide (mPR-R) in patients with untreated multiple myeloma (MM). A noninferiority design was used, and inferiority was defined as a progression-free survival (PFS) hazard ratio (HR) of MPT-T/mPR-R <=0.82. A total of 306 patients enrolled, with a median age of 75.7 years. Median follow-up was 40.7 months. Median time on therapy was 12.1 months and 23.1 months for the 46.6% of treated patients who received maintenance, with no differences by arm. Median PFS was 21 months on MPT-T and 18.7 months on mPR-R (HR, 0.84; 95% confidence interval, 0.64 1.09). Overall survival was 52.6 months (MPT-T) vs 47.7 months (mPR-R) (P = .476). Per-protocol response rates were 63.6% (MPT-T) and 59.9% (mPR-R) (P = .557). Grade >=3 nonhematologic toxicity was 59.5% for MPT-T vs 40.0% for mPR-R (P = .001). Second malignancies were observed in 18 MPT-T patients vs 14 mPR-R patients. Quality-of-life analysis favored mPR-R by induction end (P = .007). Use of MPT-T or mPR-R in elderly patients with untreated MM demonstrates no statistical or clinically relevant differences in response rates, PFS, and OS; however, quality of life at end of induction was improved and lower toxicity reported with mPR-R. This trial was registered at www.clinicaltrials.gov as #NCT00602641. PMID- 26157078 TI - Mycetoma of the foot--diagnosis of the etiologic agent and surgical treatment. PMID- 26157077 TI - Evaluation of symptom checkers for self diagnosis and triage: audit study. AB - OBJECTIVE: To determine the diagnostic and triage accuracy of online symptom checkers (tools that use computer algorithms to help patients with self diagnosis or self triage). DESIGN: Audit study. SETTING: Publicly available, free symptom checkers. PARTICIPANTS: 23 symptom checkers that were in English and provided advice across a range of conditions. 45 standardized patient vignettes were compiled and equally divided into three categories of triage urgency: emergent care required (for example, pulmonary embolism), non-emergent care reasonable (for example, otitis media), and self care reasonable (for example, viral upper respiratory tract infection). MAIN OUTCOME MEASURES: For symptom checkers that provided a diagnosis, our main outcomes were whether the symptom checker listed the correct diagnosis first or within the first 20 potential diagnoses (n=770 standardized patient evaluations). For symptom checkers that provided a triage recommendation, our main outcomes were whether the symptom checker correctly recommended emergent care, non-emergent care, or self care (n=532 standardized patient evaluations). RESULTS: The 23 symptom checkers provided the correct diagnosis first in 34% (95% confidence interval 31% to 37%) of standardized patient evaluations, listed the correct diagnosis within the top 20 diagnoses given in 58% (55% to 62%) of standardized patient evaluations, and provided the appropriate triage advice in 57% (52% to 61%) of standardized patient evaluations. Triage performance varied by urgency of condition, with appropriate triage advice provided in 80% (95% confidence interval 75% to 86%) of emergent cases, 55% (47% to 63%) of non-emergent cases, and 33% (26% to 40%) of self care cases (P<0.001). Performance on appropriate triage advice across the 23 individual symptom checkers ranged from 33% (95% confidence interval 19% to 48%) to 78% (64% to 91%) of standardized patient evaluations. CONCLUSIONS: Symptom checkers had deficits in both triage and diagnosis. Triage advice from symptom checkers is generally risk averse, encouraging users to seek care for conditions where self care is reasonable. PMID- 26157079 TI - An unusual appearing skin lesion from Penicillium marneffei infection in an AIDS patient in central China. PMID- 26157080 TI - Abnormal extra heartbeats may be modifiable risk factor for heart failure, study shows. PMID- 26157081 TI - Speech recognition in the radiology department: a systematic review. AB - OBJECTIVE: To conduct a systematic review of the literature describing the impact of speech recognition systems on report error rates and productivity in radiology departments. METHODS: The search was conducted for relevant papers published from January 1992 to October 2013. Comparative studies reporting any of the following outcomes were selected: error rates, departmental productivity, and radiologist productivity. The retrieved studies were assessed for quality and risk of bias. RESULTS: The literature search identified 85 potentially relevant publications, but, based on the inclusion and exclusion criteria, only 20 were included. Most studies were before and after assessments with no control group. There was a large amount of heterogeneity due to differences in the imaging modalities assessed and the outcomes measured. The percentage of reports containing at least one error varied from 4.8% to 89% for speech recognition, and from 2.1% to 22% for transcription. Departmental productivity was improved with decreases in report turnaround times varying from 35% to 99%. Most studies found a lengthening of radiologist dictation time. CONCLUSION: Overall gains in departmental productivity were high, but radiologist productivity, as measured by the time to produce a report, was diminished. PMID- 26157082 TI - Lifting the weight of a diagnosis-related groups family change: a comparison between refined and non-refined DRG systems for top-down cost accounting and efficiency indicators. AB - Public healthcare providers in all Spanish Regions - Autonomous Communities (ACs) use All Patients Diagnosis-Related Groups (AP-DRGs) for billing non-insured patients, cost accounting and inpatient efficiency indicators. A national migration to All Patients Refined Diagnosis-Related Groups (APR-DRGs) has been scheduled for 2016. The analysis was performed on 202,912 inpatient care episodes ranging from 2005 to 2010. All episodes were grouped using AP-DRG v25.0 and APR DRG v24.0. Normalised DRG weight variations for an AP-DRG to APR-DRG migration scenario were calculated and compared. Major differences exist between normalised weights for inpatient episodes depending on the DRGs family used. The usage of the APR-DRG system in Spain without any adjustments, as it was developed in the United States, should be approached with care. In order to avoid reverse incentives and provider financial risks, coding practices should be reviewed and structural differences between DRG families taken into account. PMID- 26157083 TI - The role of information and communication technology in the transformation of the healthcare business model: a case study of Slovenia. AB - BACKGROUND: The Slovenian healthcare business model (BM) has largely failed to integrate information and communication technologies (ICT) into its operational context, instead maintaining its rigid structure and traditional 'way of doing business'wo managers of public clinics). RESULTS: Findings present a roadmap for the redefinition of BM elements and the transformation of the Slovenian healthcare BM. It includes the specific reconfiguration of BM actors and their interactions, and the application of advanced ICT solutions, which could facilitate more effective utilisation of healthcare resources and promote an improved delivery of healthcare services and products. CONCLUSION: The presented development approach and derived conceptual solution could be transferable to other countries with similar socio-economic characteristics and comparable healthcare systems, subject to certain adjustments and inclusion of national specifics. PMID- 26157084 TI - Stakeholder analysis for adopting a personal health record standard in Korea. AB - BACKGROUND: Interest in health information exchanges (HIEs) is increasing. Several countries have adopted core health data standards with appropriate strategies. OBJECTIVE: This study was conducted to determine the feasibility of a continuity of care record (CCR) as the standard for an electronic version of the official transfer note and the HIE in Korean healthcare. METHOD: A technical review of the CCR standard and analysis of stakeholders' views were undertaken. Transfer notes were reviewed and matched with CCR standard categories. The standard for the Korean coding system was selected. Stakeholder analysis included an online survey of members of the Korean Society of Medical Informatics, a public hearing to derive opinions of consumers, doctors, vendors, academic societies and policy makers about the policy process, and a focus group meeting with EMR vendors to determine which HIE objects were technically applicable. RESULTS: Data objects in the official transfer note form matched CCR standards. Korean Classification of Diseases, Korean Standard Terminology of Medicine, Electronic Data Interchange code (EDI code), Logical Observation Identifiers Names and Codes, and Korean drug codes (KD code) were recommended as the Korean coding standard.'Social history', 'payers', and 'encounters' were mostly marked as optional or unnecessary sections, and 'allergies', 'alerts', 'medication list', 'problems/diagnoses', 'results',and 'procedures' as mandatory. Unlike the US, 'social history' was considered optional and 'advance directives' mandatory.At the public hearing there was some objection from the Korean Medical Association to the HIE on legal grounds in termsof intellectual property and patients' personal information. Other groups showed positive or neutral responses. Focus group members divided CCR data objects into three phases based onpredicted adoption time in CCR: (i) immediate adoption; (ii) short-term adoption ('alerts', 'family history'); and (iii) long-term adoption ('results', 'advanced directives', 'functional status', 'medical equipment', 'vital signs', 'plan of care', 'social history'). CONCLUSION: There were no technical problems in generating the CCR standard document from EMRs. Matters of concern that arose from study results should be resolved with time and consultation. PMID- 26157085 TI - Reproducing increased dopamine with infection to evaluate the role of parasite encoded tyrosine hydroxylase activity. PMID- 26157086 TI - Reply to "reproducing increased dopamine with infection to evaluate the role of parasite-encoded tyrosine hydroxylase activity". PMID- 26157087 TI - Correction for Hervet et al., protein kinase LegK2 is a type IV secretion system effector involved in endoplasmic reticulum recruitment and intracellular replication of Legionella pneumophila. PMID- 26157088 TI - Correction for Massari et al., meningococcal porin PorB prevents cellular apoptosis in a Toll-like receptor 2- and NF-kappaB-independent manner. PMID- 26157089 TI - Correction for Ma et al., two functional type VI secretion systems in avian pathogenic Escherichia coli are involved in different pathogenic pathways. PMID- 26157091 TI - More day surgery and generic prescribing could increase productivity, King's Fund report says. PMID- 26157092 TI - Projects related to respiratory infectious diseases, gastrointestinal diseases, viral hepatitis, and miscellaneous infection. PMID- 26157093 TI - Molecular tests for rapid detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis. PMID- 26157094 TI - Direct identification and quantification of host and viral miRNAs after influenza infection using the next generation ultra-high throughput DNA sequencer. PMID- 26157095 TI - H5N1 virus resistant to antiviral drug. PMID- 26157096 TI - Live recombinant Salmonella oral vaccine against avian influenza viruses. PMID- 26157097 TI - The role of cathelicidin in control of Helicobacter pylori colonisation in the stomach. PMID- 26157098 TI - Institutional risk factors for outbreaks of acute gastroenteritis in homes for the elderly: a retrospective cohort analysis. PMID- 26157099 TI - Liver cirrhosis-specific glycoforms of serum proteins in chronic hepatitis B infection: identification by lectin affinity chromatography and quantitative proteomic profiling. PMID- 26157100 TI - Role of hepatitis B virus X protein in liver cancer. PMID- 26157101 TI - Viral mutant discovery in hepatitis B virus quasi-species in patients undergoing long-term lamivudine treatment. PMID- 26157102 TI - Identification of hepatitis B virus DNA reverse transcriptase variants associated with partial response to entecavir. PMID- 26157103 TI - Modulation of cytokine responses by adrenomedullin and adrenomedullin binding protein-1 in macrophages: a novel pathway in sepsis. PMID- 26157104 TI - Association of human adenovirus-36 with diabetes, adiposity, and dyslipidaemia in Hong Kong Chinese. PMID- 26157105 TI - An Accelerometer as an Alternative to a Force Plate for the Step-Up-and-Over Test. AB - The step-up-and-over test has been used successfully to examine knee function after knee injury. Knee function is quantified using the following variables extracted from force plate data: the maximal force exerted during the lift, the maximal impact force at landing, and the total time to complete the step. For various reasons, including space and cost, it is unlikely that all clinicians will have access to a force plate. The purpose of the study was to determine if the step-up-and-over test could be simplified by using an accelerometer. The step up-and-over test was performed by 17 healthy young adults while being measured with both a force plate and a 3-axis accelerometer mounted at the low back. Results showed that the accelerometer and force plate measures were strongly correlated for all 3 variables (r = .90-.98, Ps < .001) and that the accelerometer values for the lift and impact indices were 6-7% higher (Ps < .01) and occurred 0.07-0.1 s later than the force plate (Ps < .05). The accelerometer returned values highly correlated to those from a force plate. Compared with a force plate, a wireless, 3-axis accelerometer is a less expensive and more portable system with which to measure the step-up-and-over test. PMID- 26157106 TI - Promoting equality for ethnic minority NHS staff--what works? PMID- 26157107 TI - An Endplate-Based Joint Coordinate System for Measuring Kinematics in Normal and Abnormally-Shaped Lumbar Vertebrae. AB - Vertebral level-dependent, angular, and linear translations of the spine have been measured in 2D and 3D using several imaging methods to quantify postural changes due to loading conditions and tasks. Here, we propose and validate a semiautomated method for measuring lumbar intervertebral angles and translations from upright MRI images using an endplate-based, joint coordinate system (JCS). This method was validated using 3D printed structures, representing intervertebral discs (IVD) at predetermined angles and heights, which were positioned between adjacent cadaveric vertebrae as a gold standard. Excellent agreement between our measurements and the gold standard was found for intervertebral angles in all anatomical planes (ICC > .997) and intervertebral distance measurements (ICC > .949). The proposed endplate-based JCS was compared with the vertebral body-based JCS proposed by the International Society of Biomechanics (ISB) using the 3D printed structures placed between 3 adjacent vertebrae from a cadaver with scoliosis. The endplate-based method was found to have better agreement with angles in the sagittal plane (ICC = 0.985) compared with the vertebral body-based method (ICC = .280). Thus, this method is accurate for measuring 3D intervertebral angles in the healthy and diseased lumbar spine. PMID- 26157108 TI - Suicide in Canada: impact of injuries with undetermined intent on regional rankings. AB - The impact of underreporting or misclassifying suicides as injuries with undetermined intent is rarely evaluated. We assessed whether undetermined injury deaths influenced provincial rankings of suicide in Canada, using 2 735 152 Canadians followed for mortality from 1991 to 2001. We found that suicide rates increased by up to 26.5% for men and 37.7% for women after including injuries with undetermined intent, shifting provincial rankings of suicide. Attention to the stigma of suicide and to coding suicides as injuries with undetermined intent is merited for surveillance and prevention. PMID- 26157109 TI - Safety in Numbers for walkers and bicyclists: exploring the mechanisms. PMID- 26157110 TI - Do Knee Moments Normalized to Measures of Knee Cartilage Area Better Classify the Severity of Knee Osteoarthritis? AB - Investigations of joint loading in knee osteoarthritis (OA) typically normalize the knee adduction moment to global measures of body size (eg, body mass, height) to allow comparison between individuals. However, such measurements may not reflect knee size. This study used a morphometric measurement of the cartilage surface area on the medial tibial plateau, which better represents medial knee size. This study aimed to determine whether normalizing the peak knee adduction moment and knee adduction moment impulse during gait to the medial tibial bone cartilage interface could classify radiographic knee OA severity more accurately than traditional normalization techniques. Individuals with mild (N = 22) and severe (N = 17) radiographic knee OA participated. The medial tibial bone cartilage interface was quantified from magnetic resonance imaging scans. Gait analysis was performed, and the peak knee adduction moment and knee adduction moment impulse were calculated in nonnormalized units and normalized to body mass, body weight * height, and the medial tibial bone-cartilage interface. Receiver operating characteristic curves compared the ability of each knee adduction moment normalization technique to classify participants according to radiographic disease severity. No normalization technique was superior at distinguishing between OA severities. Knee adduction moments normalized to medial knee size were not more sensitive to OA severity. PMID- 26157111 TI - Cohort Profile: Health Watch-a 30-year prospective cohort study of Australian petroleum industry workers. PMID- 26157112 TI - Comment on: Clinical cure rates in subjects treated with azithromycin for community-acquired respiratory tract infections caused by azithromycin susceptible or azithromycin-resistant Streptococcus pneumoniae: analysis of Phase 3 clinical trial data. PMID- 26157113 TI - A Constitutively Active Allele of Phytochrome B Maintains Circadian Robustness in the Absence of Light. AB - The sensitivity of the circadian system to light allows entrainment of the clock, permitting coordination of plant metabolic function and flowering time across seasons. Light affects the circadian system via both photoreceptors, such as phytochromes and cryptochromes, and sugar production by photosynthesis. In the present study, we introduce a constitutively active version of phytochrome B Y276H (YHB) into both wild-type and phytochrome null backgrounds of Arabidopsis (Arabidopsis thaliana) to distinguish the effects of photoreceptor signaling on clock function from those of photosynthesis. We find that the YHB mutation is sufficient to phenocopy red light input into the circadian mechanism and to sustain robust rhythms in steady-state mRNA levels even in plants grown without light or exogenous sugars. The pace of the clock is insensitive to light intensity in YHB plants, indicating that light input to the clock is constitutively activated by this allele. Mutation of YHB so that it is retained in the cytoplasm abrogates its effects on clock function, indicating that nuclear localization of phytochrome is necessary for its clock regulatory activity. We also demonstrate a role for phytochrome C as part of the red light sensing network that modulates phytochrome B signaling input into the circadian system. Our findings indicate that phytochrome signaling in the nucleus plays a critical role in sustaining robust clock function under red light, even in the absence of photosynthesis or exogenous sources of energy. PMID- 26157114 TI - Identification, Functional Characterization, and Evolution of Terpene Synthases from a Basal Dicot. AB - Bay laurel (Laurus nobilis) is an agriculturally and economically important dioecious tree in the basal dicot family Lauraceae used in food and drugs and in the cosmetics industry. Bay leaves, with their abundant monoterpenes and sesquiterpenes, are used to impart flavor and aroma to food, and have also drawn attention in recent years because of their potential pharmaceutical applications. To identify terpene synthases (TPSs) involved in the production of these volatile terpenes, we performed RNA sequencing to profile the transcriptome of L. nobilis leaves. Bioinformatic analysis led to the identification of eight TPS complementary DNAs. We characterized the enzymes encoded by three of these complementary DNAs: a monoterpene synthase that belongs to the TPS-b clade catalyzes the formation of mostly 1,8-cineole; a sesquiterpene synthase belonging to the TPS-a clade catalyzes the formation of mainly cadinenes; and a diterpene synthase of the TPS-e/f clade catalyzes the formation of geranyllinalool. Comparison of the sequences of these three TPSs indicated that the TPS-a and TPS b clades of the TPS gene family evolved early in the evolution of the angiosperm lineage, and that geranyllinalool synthase activity is the likely ancestral function in angiosperms of genes belonging to an ancient TPS-e/f subclade that diverged from the kaurene synthase gene lineages before the split of angiosperms and gymnosperms. PMID- 26157115 TI - Extra-Large G Proteins Expand the Repertoire of Subunits in Arabidopsis Heterotrimeric G Protein Signaling. AB - Heterotrimeric G proteins, consisting of Galpha, Gbeta, and Ggamma subunits, are a conserved signal transduction mechanism in eukaryotes. However, G protein subunit numbers in diploid plant genomes are greatly reduced as compared with animals and do not correlate with the diversity of functions and phenotypes in which heterotrimeric G proteins have been implicated. In addition to GPA1, the sole canonical Arabidopsis (Arabidopsis thaliana) Galpha subunit, Arabidopsis has three related proteins: the extra-large GTP-binding proteins XLG1, XLG2, and XLG3. We demonstrate that the XLGs can bind Gbetagamma dimers (AGB1 plus a Ggamma subunit: AGG1, AGG2, or AGG3) with differing specificity in yeast (Saccharomyces cerevisiae) three-hybrid assays. Our in silico structural analysis shows that XLG3 aligns closely to the crystal structure of GPA1, and XLG3 also competes with GPA1 for Gbetagamma binding in yeast. We observed interaction of the XLGs with all three Gbetagamma dimers at the plasma membrane in planta by bimolecular fluorescence complementation. Bioinformatic and localization studies identified and confirmed nuclear localization signals in XLG2 and XLG3 and a nuclear export signal in XLG3, which may facilitate intracellular shuttling. We found that tunicamycin, salt, and glucose hypersensitivity and increased stomatal density are agb1-specific phenotypes that are not observed in gpa1 mutants but are recapitulated in xlg mutants. Thus, XLG-Gbetagamma heterotrimers provide additional signaling modalities for tuning plant G protein responses and increase the repertoire of G protein heterotrimer combinations from three to 12. The potential for signal partitioning and competition between the XLGs and GPA1 is a new paradigm for plant-specific cell signaling. PMID- 26157116 TI - Rapid Development of gp120-Focused Neutralizing B Cell Responses during Acute Simian Immunodeficiency Virus Infection of African Green Monkeys. AB - The initial phases of acute human immunodeficiency virus type 1 (HIV-1) infection may be critical for development of effective envelope (Env)-specific antibodies capable of impeding the establishment of the latent pool of HIV-1-infected CD4(+) T cells, preventing virus-induced immune hyperactivation to limit disease progression and blocking vertical virus transmission. However, the initial systemic HIV-1 Env-specific antibody response targets gp41 epitopes and fails to control acute-phase viremia. African-origin, natural simian immunodeficiency virus (SIV) hosts do not typically progress to AIDS and rarely postnatally transmit virus to their infants, despite high milk viral loads. Conversely, SIV infected rhesus macaques (RMs), Asian-origin nonnatural SIV hosts, sustain pathogenic SIV infections and exhibit higher rates of postnatal virus transmission. In this study, of acute SIV infection, we compared the initial systemic Env-specific B cell responses of AGMs and RMs in order to probe potential factors influencing the lack of disease progression observed in AGMs. AGMs developed higher-magnitude plasma gp120-specific IgA and IgG responses than RMs, whereas RMs developed more robust gp140-directed IgG responses. These gp120 focused antibody responses were accompanied by rapid autologous neutralizing responses during acute SIV infection in AGMs compared to RMs. Moreover, acute SIV infection elicited a higher number of circulating Env-specific memory B cells in peripheral blood of AGMs than in the blood of RMs. These findings indicate that AGMs have initial systemic Env-specific B cell responses to SIV infection distinct from those of a nonnatural SIV host, resulting in more functional SIV specific humoral responses, which may be involved in impairing pathogenic disease progression and minimizing postnatal transmission. IMPORTANCE: Due to the worldwide prevalence of HIV-1 infections, development of a vaccine to prevent infection or limit the viral reservoir remains an important goal. HIV-1-infected humans, as well as SIV-infected nonnatural SIV hosts, develop pathogenic infections and readily transmit the virus to their infants. Conversely, natural SIV hosts do not develop pathogenic infections and rarely transmit the virus to their infants. The immunologic factors contributing to these favorable outcomes in natural SIV hosts could prove invaluable for directing HIV-1 vaccine and therapy design. This study identified distinctions in the specificity and function of the initial systemic SIV envelope-specific B cell response that developed during acute SIV infection in natural and nonnatural SIV host species. Identification of distinct acute B cell responses in natural SIV hosts may inform vaccine strategies seeking to elicit similar responses prior to or during the initial phases of acute HIV-1 infection. PMID- 26157117 TI - Human and Murine IFIT1 Proteins Do Not Restrict Infection of Negative-Sense RNA Viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae Families. AB - Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5'-triphosphates (5'-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5'-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1(-/-) and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1(-/-) and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5' ends of IAV gene segments. The affinity for 5' ppp RNA was approximately 10-fold lower than that for non-2'-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. IMPORTANCE: Negative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this study, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis both in vitro and in vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses. PMID- 26157118 TI - Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy Species Barriers by Use of Real-Time Conversion. AB - The propensity for transspecies prion transmission is related to the structural characteristics of the enciphering and new host PrP, although the exact mechanism remains incompletely understood. The effects of variability in prion protein on cross-species prion transmission have been studied with animal bioassays, but the influence of prion protein structure versus that of host cofactors (e.g., cellular constituents, trafficking, and innate immune interactions) remains difficult to dissect. To isolate the effects of protein-protein interactions on transspecies conversion, we used recombinant PrP(C) and real-time quaking-induced conversion (RT-QuIC) and compared chronic wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE) prions. To assess the impact of transmission to a new species, we studied feline CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]). We cross-seeded fCWD and FSE into each species' full-length, recombinant PrP(C) and measured the time required for conversion to the amyloid (PrP(Res)) form, which we describe here as the rate of amyloid conversion. These studies revealed the following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii) conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as homologous sCJD prions. These results suggest that (i) at the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE and (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated. IMPORTANCE: We demonstrate that bovine spongiform encephalopathy prions maintain their transspecies conversion characteristics upon passage to cats but that chronic wasting disease prions adapt to the cat and are distinguishable from the original prion. Additionally, we showed that chronic wasting disease prions are effective at seeding the conversion of normal human prion protein to an amyloid conformation, perhaps the first step in crossing the species barrier. PMID- 26157119 TI - Microplitis demolitor Bracovirus Proviral Loci and Clustered Replication Genes Exhibit Distinct DNA Amplification Patterns during Replication. AB - Polydnaviruses are large, double-stranded DNA viruses that are beneficial symbionts of parasitoid wasps. Polydnaviruses in the genus Bracovirus (BVs) persist in wasps as proviruses, and their genomes consist of two functional components referred to as proviral segments and nudivirus-like genes. Prior studies established that the DNA domains where proviral segments reside are amplified during replication and that segments within amplified loci are circularized before packaging into nucleocapsids. One DNA domain where nudivirus like genes are located is also amplified but never packaged into virions. We recently sequenced the genome of the braconid Microplitis demolitor, which carries M. demolitor bracovirus (MdBV). Here, we took advantage of this resource to characterize the DNAs that are amplified during MdBV replication using a combination of Illumina and Pacific Biosciences sequencing approaches. The results showed that specific nucleotide sites identify the boundaries of amplification for proviral loci. Surprisingly, however, amplification of loci 3, 4, 6, and 8 produced head-to-tail concatemeric intermediates; loci 1, 2, and 5 produced head-to-head/tail-to-tail concatemers; and locus 7 yielded no identified concatemers. Sequence differences at amplification junctions correlated with the types of amplification intermediates the loci produced, while concatemer processing gave rise to the circularized DNAs that are packaged into nucleocapsids. The MdBV nudivirus-like gene cluster was also amplified, albeit more weakly than most proviral loci and with nondiscrete boundaries. Overall, the MdBV genome exhibited three patterns of DNA amplification during replication. Our data also suggest that PacBio sequencing could be useful in studying the replication intermediates produced by other DNA viruses. IMPORTANCE: Polydnaviruses are of fundamental interest because they provide a novel example of viruses evolving into beneficial symbionts. All polydnaviruses are associated with insects called parasitoid wasps, which are of additional applied interest because many are biological control agents of pest insects. Polydnaviruses in the genus Bracovirus (BVs) evolved ~100 million years ago from an ancestor related to the baculovirus-nudivirus lineage but have also established many novelties due to their symbiotic lifestyle. These include the fact that BVs are transmitted only vertically as proviruses and produce replication-defective virions that package only a portion of the viral genome. Here, we studied Microplitis demolitor bracovirus (MdBV) and report that its genome exhibits three distinct patterns of DNA amplification during replication. We also identify several previously unknown features of BV genomes that correlate with these different amplification patterns. PMID- 26157120 TI - Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release. AB - Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n = 11) or persistence (n = 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P < 0.01) and miR-885-5p (Pcorrected < 0.05) and a decrease in miR-494 (Pcorrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P < 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco based You Find Out (UFO) Study (n = 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR 885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P < 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans. IMPORTANCE: MicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe liver disease. We profiled plasma miRNAs in injection drug users before, during, and (in the people with resolution) after HCV infection. We discovered miRNA signatures of acute and persistent viremia and confirmed these findings two ways: (i) in a separate cohort of people with newly acquired HCV infection and (ii) in an HCV cell culture system. Our results demonstrate that acute HCV infection induces early changes in the abundance of specific plasma miRNAs that may affect the host response to HCV infection. PMID- 26157121 TI - The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis. AB - Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. IMPORTANCE: Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the small intestinal GALT are the essential early sites of prion accumulation. Furthermore, congruent infection with a large intestinal helminth (worm) around the time of oral prion exposure did not affect disease pathogenesis. This is important for our understanding of the factors that influence the risk of prion infection and the preclinical diagnosis of disease. The detection of prions within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, our data suggest that using these biopsy specimens may miss individuals in the early stages of oral prion infection and significantly underestimate the disease prevalence. PMID- 26157122 TI - Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate. AB - Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response. IMPORTANCE: Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation. PMID- 26157123 TI - Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies. AB - Since it was first recognized in 2004 that human parechoviruses (HPeV) are a significant cause of central nervous system and neonatal sepsis, their clinical importance, primarily in children, has started to emerge. Intravenous immunoglobulin treatment is the only treatment available in such life-threatening cases and has given moderate success. Direct inhibition of parechovirus infection using monoclonal antibodies is a potential treatment. We have developed two neutralizing monoclonal antibodies against HPeV1 and HPeV2, namely, AM18 and AM28, which also cross-neutralize other viruses. Here, we present the mapping of their epitopes using peptide scanning, surface plasmon resonance, fluorescence based thermal shift assays, electron cryomicroscopy, and image reconstruction. We determined by peptide scanning and surface plasmon resonance that AM18 recognizes a linear epitope motif including the arginine-glycine-aspartic acid on the C terminus of capsid protein VP1. This epitope is normally used by the virus to attach to host cell surface integrins during entry and is found in 3 other viruses that AM18 neutralizes. Therefore, AM18 is likely to cause virus neutralization by aggregation and by blocking integrin binding to the capsid. Further, we show by electron cryomicroscopy, three-dimensional reconstruction, and pseudoatomic model fitting that ordered RNA interacts with HPeV1 VP1 and VP3. AM28 recognizes quaternary epitopes on the capsid composed of VP0 and VP3 loops from neighboring pentamers, thereby increasing the RNA accessibility temperature for the virus-AM28 complex compared to the virus alone. Thus, inhibition of RNA uncoating probably contributes to neutralization by AM28. IMPORTANCE: Human parechoviruses can cause mild infections to severe diseases in young children, such as neonatal sepsis, encephalitis, and cardiomyopathy. Intravenous immunoglobulin treatment is the only treatment available in such life-threatening cases. In order to develop more targeted treatment, we have searched for human monoclonal antibodies that would neutralize human parechoviruses 1 and 2, associated with mild infections such as gastroenteritis and severe infections of the central nervous system, and thus allow safe treatment. In the current study, we show how two such promising antibodies interact with the virus, modeling the atomic interactions between the virus and the antibody to propose how neutralization occurs. Both antibodies can cause aggregation; in addition, one antibody interferes with the virus recognizing its target cell, while the other, recognizing only the whole virus, inhibits the genome uncoating and replication in the cell. PMID- 26157124 TI - Measles Virus Infection Inactivates Cellular Protein Phosphatase 5 with Consequent Suppression of Sp1 and c-Myc Activities. AB - Measles virus (MeV) causes several unique syndromes, including transient immunosuppression. To clarify the cellular responses to MeV infection, we previously analyzed a MeV-infected epithelial cell line and a lymphoid cell line by microarray and showed that the expression of numerous genes was up- or downregulated in the epithelial cells. In particular, there was a characteristic comprehensive downregulation of housekeeping genes during late stage infection. To identify the mechanism underlying this phenomenon, we examined the phosphorylation status of transcription factors and kinase/phosphatase activities in epithelial cells after infection. MeV infection inactivated cellular protein phosphatase 5 (PP5) that consequently inactivated DNA-dependent protein kinase, which reduced Sp1 phosphorylation levels, and c-Myc degradation, both of which downregulated the expression of many housekeeping genes. In addition, intracellular accumulation of viral nucleocapsid inactivated PP5 and subsequent downstream responses. These findings demonstrate a novel strategy of MeV during infection, which causes the collapse of host cellular functions. IMPORTANCE: Measles virus (MeV) is one of the most important pathogens in humans. We previously showed that MeV infection induces the comprehensive downregulation of housekeeping genes in epithelial cells. By examining this phenomenon, we clarified the molecular mechanism underlying the constitutive expression of housekeeping genes in cells, which is maintained by cellular protein phosphatase 5 (PP5) and DNA-dependent protein kinase. We also demonstrated that MeV targets PP5 for downregulation in epithelial cells. This is the first report to show how MeV infection triggers a reduction in overall cellular functions of infected host cells. Our findings will help uncover unique pathogenicities caused by MeV. PMID- 26157125 TI - Comparative Phylodynamics of Rabbit Hemorrhagic Disease Virus in Australia and New Zealand. AB - The introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand during the 1990s as a means of controlling feral rabbits is an important case study in viral emergence. Both epidemics are exceptional in that the founder viruses share an origin and the timing of their release is known, providing a unique opportunity to compare the evolution of a single virus in distinct naive populations. We examined the evolution and spread of RHDV in Australia and New Zealand through a genome-wide evolutionary analysis, including data from 28 newly sequenced RHDV field isolates. Following the release of the Australian inoculum strain into New Zealand, no subsequent mixing of the populations occurred, with viruses from both countries forming distinct groups. Strikingly, the rate of evolution in the capsid gene was higher in the Australian viruses than in those from New Zealand, most likely due to the presence of transient deleterious mutations in the former. However, estimates of both substitution rates and population dynamics were strongly sample dependent, such that small changes in sample composition had an important impact on evolutionary parameters. Phylogeographic analysis revealed a clear spatial structure in the Australian RHDV strains, with a major division between those viruses from western and eastern states. Importantly, RHDV sequences from the state where the virus was first released, South Australia, had the greatest diversity and were diffuse throughout both geographic lineages, such that this region was likely a source population for the subsequent spread of the virus across the country. IMPORTANCE: Most studies of viral emergence lack detailed knowledge about which strains were founders for the outbreak or when these events occurred. Hence, the human mediated introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand from known starting stocks provides a unique opportunity to understand viral evolution and emergence. Within Australia, we revealed a major phylogenetic division between viruses sampled from the east and west of the country, with both regions likely seeded by viruses from South Australia. Despite their common origins, marked differences in evolutionary rates were observed between the Australian and New Zealand RHDV, which led to conflicting conclusions about population growth rates. An analysis of mutational patterns suggested that evolutionary rates have been elevated in the Australian viruses, at least in part due to the presence of low-fitness (deleterious) variants that have yet to be selectively purged. PMID- 26157126 TI - The Vaginal Acquisition and Dissemination of HIV-1 Infection in a Novel Transgenic Mouse Model Is Facilitated by Coinfection with Herpes Simplex Virus 2 and Is Inhibited by Microbicide Treatment. AB - Epidemiological studies have demonstrated that herpes simplex virus 2 (HSV-2) infection significantly increases the risk of HIV-1 acquisition, thereby contributing to the expanding HIV-1 epidemic. To investigate whether HSV-2 infection directly facilitates mucosal HIV-1 acquisition, we used our transgenic hCD4/R5/cT1 mouse model which circumvents major entry and transcription blocks preventing murine HIV-1 infection by targeting transgenic expression of human CD4, CCR5, and cyclin T1 genes to CD4(+) T cells and myeloid-committed cells. Productive infection of mucosal leukocytes, predominantly CD4(+) T cells, was detected in all hCD4/R5/cT1 mice intravaginally challenged with an HIV-1 infectious molecular clone, HIV-Du151.2env-NLuc, which expresses an env gene (C.Du151.2) cloned from an acute heterosexually infected woman and a NanoLuc luciferase reporter gene. Lower genital tract HIV-1 infection after HIV Du151.2env-NLuc intravaginal challenge was increased ~4-fold in hCD4/R5/cT1 mice coinfected with HSV-2. Furthermore, HIV-1 dissemination to draining lymph nodes was detected only in HSV-2-coinfected mice. HSV-2 infection stimulated local infiltration and activation of CD4(+) T cells and dendritic cells, likely contributing to the enhanced HIV-1 infection and dissemination in HSV-2 coinfected mice. We then used this model to demonstrate that a novel gel containing tenofovir disoproxil fumarate (TDF), the more potent prodrug of tenofovir (TFV), but not the TFV microbicide gel utilized in the recent CAPRISA 004, VOICE (Vaginal and Oral Interventions to Control the Epidemic), and FACTS 001 clinical trials, was effective as preexposure prophylaxis (PrEP) to completely prevent vaginal HIV-1 infection in almost half of HSV-2-coinfected mice. These results also support utilization of hCD4/R5/cT1 mice as a highly reproducible immunocompetent preclinical model to evaluate HIV-1 acquisition across the female genital tract. IMPORTANCE: Multiple epidemiological studies have reported that genital herpes simplex virus 2 (HSV-2) infection increases the risk of HIV-1 sexual acquisition by severalfold. Understanding the underlying mechanisms by which HSV-2 facilitates HIV-1 infection and optimizing the efficacy of therapies to inhibit HIV-1 infection during HSV-2 coinfection should contribute to reducing HIV-1 transmission. Using our novel transgenic hCD4/R5/cT1 mouse model infectible with HIV-1, we demonstrated that HSV-2 infection enhances vaginal transmission and dissemination of HIV-1 infection while stimulating recruitment and activation of CD4(+) T cells and dendritic cells in the lower genital tract. HIV acquisition by hCD4/R5/cT1 mice vaginally coinfected with HSV 2 could be completely prevented in almost half the mice by preexposure prophylaxis (PrEP) with a novel gel containing tenofovir disoproxil fumarate (TDF), the tenofovir prodrug, but not with the tenofovir microbicide gel utilized in CAPRISA-004, VOICE, and FACTS-001 clinical trials. The hCD4/R5/cT1 mice represent a new preclinical mouse model to evaluate vaginal HIV-1 acquisition. PMID- 26157127 TI - Generation of a Recombinant Akabane Virus Expressing Enhanced Green Fluorescent Protein. AB - We generated a recombinant Akabane virus (AKAV) expressing enhanced green fluorescence protein (eGFP-AKAV) by using reverse genetics. We artificially constructed an ambisense AKAV S genome encoding N/NSs on the negative-sense strand, and eGFP on the positive-sense strand with an intergenic region (IGR) derived from the Rift Valley fever virus (RVFV) S genome. The recombinant virus exhibited eGFP fluorescence and had a cytopathic effect in cell cultures, even after several passages. These results indicate that the gene encoding eGFP in the ambisense RNA could be stably maintained. Transcription of N/NSs and eGFP mRNAs of eGFP-AKAV was terminated within the IGR. The mechanism responsible for this appears to be different from that in RVFV, where the termination sites for N and NSs are determined by a defined signal sequence. We inoculated suckling mice intraperitoneally with eGFP-AKAV, which resulted in neurological signs and lethality equivalent to those seen for the parent AKAV. Fluorescence from eGFP in frozen brain slices from the eGFP-AKAV-infected mice was localized to the cerebellum, pons, and medulla oblongata. Our approach to producing a fluorescent virus, using an ambisense genome, helped obtain eGFP-AKAV, a fluorescent bunyavirus whose viral genes are intact and which can be easily visualized. IMPORTANCE: AKAV is the etiological agent of arthrogryposis-hydranencephaly syndrome in ruminants, which causes considerable economic loss to the livestock industry. We successfully generated a recombinant enhanced green fluorescent protein-tagged AKAV containing an artificial ambisense S genome. This virus could become a useful tool for analyzing AKAV pathogenesis in host animals. In addition, our approach of using an ambisense genome to generate an orthobunyavirus stably expressing a foreign gene could contribute to establishing alternative vaccine strategies, such as bivalent vaccine virus constructs, for veterinary use against infectious diseases. PMID- 26157128 TI - Systemic Foot-and-Mouth Disease Vaccination in Cattle Promotes Specific Antibody Secreting Cells at the Respiratory Tract and Triggers Local Anamnestic Responses upon Aerosol Infection. AB - Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high-payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days postvaccination (dpv), reaching a plateau at 29 dpv. FMDV specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, although in lower numbers. At 29 dpv, a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animals (n = 10) exhibited FMD symptoms after oronasal challenge at 30 dpv. Three days postinfection, a large increase in ASC numbers and rapid isotype switches to IgG1 were observed, particularly in LN draining virus replication sites already described. These results indicate for the first time that systemic FMD vaccination in cattle effectively promotes the presence of anti-FMDV ASC in lymphoid tissues associated with the respiratory system. Oronasal infection triggered an immune reaction compatible with a local anamnestic response upon contact with the replicating FMDV, suggesting that FMD vaccination induces the circulation of virus-specific B lymphocytes, including memory B cells that differentiate into ASC soon after contact with the infective virus. IMPORTANCE: Over recent decades, world animal health organizations as well as national sanitary authorities have supported the use of vaccination as an essential component of the official FMD control programs in both endemic and disease-free settings. Very few works studied the local immunity induced by FMD vaccines at the respiratory mucosa, and local responses induced in vaccinated animals after aerosol infection have not been described yet. In this work, we demonstrate for the first time that systemic FMD vaccination (i) induced the early presence of active antigen-specific ASC along the respiratory tract and (ii) prompted a rapid local antibody response in the respiratory mucosa, triggered upon oronasal challenge and congruent with a memory B-cell response. This information may help to understand novel aspects of protective responses induced by current FMD vaccines as well as to provide alternative parameters to establish protection efficiency for new vaccine developments. PMID- 26157129 TI - A Dynein Light Chain 1 Binding Motif in Rabies Virus Polymerase L Protein Plays a Role in Microtubule Reorganization and Viral Primary Transcription. AB - Rabies virus (RABV) polymerase L together with phosphoprotein P forms the PL polymerase complex that is essential for replication and transcription. However, its exact mechanism of action, interactions with cellular factors, and intracellular distribution are yet to be understood. Here by imaging a fluorescently tagged polymerase (mCherry-RABV-L), we show that L accumulates at acetylated and reorganized microtubules (MT). In silico analysis revealed a dynein light chain 1 (DLC1) binding motif in L that could mediate MT binding through dynein motors. As DLC1 binding by polymerase cofactor P is known, we compared the impact of the DLC1-binding motifs in P and L. Viruses with mutations in the respective motifs revealed that both motifs are required for efficient primary transcription, indicating that DLC1 acts as a transcription enhancer by binding to both P and L. Notably, also the levels of cellular DLC1 protein were regulated by both motifs, suggesting regulation of the DLC1 gene expression by both P and L. Finally, disruption of the motif in L resulted in a cell-type specific loss of MT localization, demonstrating that DLC1 is involved in L mediated cytoskeleton reorganization. Overall, we conclude that DLC1 acts as a transcription factor that stimulates primary RABV transcription by binding to both P and L. We further conclude that L influences MT organization and posttranslational modification, suggesting a model in which MT manipulation by L contributes to efficient intracellular transport of virus components and thus may serve as an important step in virus replication. IMPORTANCE: Regulation of rabies virus polymerase complex by viral and cellular factors thus far has not been fully understood. Although cellular dynein light chain 1 (DLC1) has been reported to increase primary transcription by binding to polymerase cofactor phosphoprotein P, the detailed mechanism is unknown, and it is also not known whether the large enzymatic polymerase subunit L is involved. By fluorescence microscopy analysis of fluorescence-tagged rabies virus L, in silico identification of a potential DLC1 binding site in L, and characterization of recombinant rabies virus mutants, we show that a DLC1 binding motif in L is involved in cytoskeleton localization and reorganization, primary transcription regulation by DLC1, and regulation of cellular DLC1 gene expression. By providing evidence for a direct contribution of a DLC1 binding motif in L, our data significantly increase the understanding of rabies virus polymerase regulation and host manipulation by the virus as well. PMID- 26157130 TI - Downregulation of Poly(ADP-Ribose) Polymerase 1 by a Viral Processivity Factor Facilitates Lytic Replication of Gammaherpesvirus. AB - In Kaposi's sarcoma-associated herpesvirus (KSHV), poly(ADP-ribose) polymerase 1 (PARP-1) acts as an inhibitor of lytic replication. Here, we demonstrate that KSHV downregulated PARP-1 upon reactivation. The viral processivity factor of KSHV (PF-8) interacted with PARP-1 and was sufficient to degrade PARP-1 in a proteasome-dependent manner; this effect was conserved in murine gammaherpesvirus 68. PF-8 knockdown in KSHV-infected cells resulted in reduced lytic replication upon reactivation with increased levels of PARP-1, compared to those in control cells. PF-8 overexpression reduced the levels of the poly(ADP-ribosyl)ated (PARylated) replication and transcription activator (RTA) and further enhanced RTA-mediated transactivation. These results suggest a novel viral mechanism for overcoming the inhibitory effect of a host factor, PARP-1, thereby promoting the lytic replication of gammaherpesvirus. IMPORTANCE: Gammaherpesviruses are important human pathogens, as they are associated with various kinds of tumors and establish latency mainly in host B lymphocytes. Replication and transcription activator (RTA) of Kaposi's sarcoma-associated herpesvirus (KSHV) is a central molecular switch for lytic replication, and its expression is tightly regulated by many host and viral factors. In this study, we investigated a viral strategy to overcome the inhibitory effect of poly(ADP-ribose) polymerase 1 (PARP-1) on RTA's activity. PARP-1, an abundant multifunctional nuclear protein, was downregulated during KSHV reactivation. The viral processivity factor of KSHV (PF 8) directly interacted with PARP-1 and was sufficient and necessary to degrade PARP-1 protein in a proteasome-dependent manner. PF-8 reduced the levels of PARylated RTA and further promoted RTA-mediated transactivation. As this was also conserved in another gammaherpesvirus, murine gammaherpesvirus 68, our results suggest a conserved viral modulation of a host inhibitory factor to facilitate its lytic replication. PMID- 26157132 TI - Cross-cultural convergence of musical features. PMID- 26157131 TI - Selective Involvement of the Checkpoint Regulator VISTA in Suppression of B-Cell, but Not T-Cell, Responsiveness by Monocytic Myeloid-Derived Suppressor Cells from Mice Infected with an Immunodeficiency-Causing Retrovirus. AB - Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ~50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness. PMID- 26157133 TI - Structure of LacY with an alpha-substituted galactoside: Connecting the binding site to the protonation site. AB - The X-ray crystal structure of a conformationally constrained mutant of the Escherichia coli lactose permease (the LacY double-Trp mutant Gly-46->Trp/Gly-262 >Trp) with bound p-nitrophenyl-alpha-d-galactopyranoside (alpha-NPG), a high affinity lactose analog, is described. With the exception of Glu-126 (helix IV), side chains Trp-151 (helix V), Glu-269 (helix VIII), Arg-144 (helix V), His-322 (helix X), and Asn-272 (helix VIII) interact directly with the galactopyranosyl ring of alpha-NPG to provide specificity, as indicated by biochemical studies and shown directly by X-ray crystallography. In contrast, Phe-20, Met-23, and Phe-27 (helix I) are within van der Waals distance of the benzyl moiety of the analog and thereby increase binding affinity nonspecifically. Thus, the specificity of LacY for sugar is determined solely by side-chain interactions with the galactopyranosyl ring, whereas affinity is increased by nonspecific hydrophobic interactions with the anomeric substituent. PMID- 26157134 TI - Dissociation of HSV gL from gH by alphavbeta6- or alphavbeta8-integrin promotes gH activation and virus entry. AB - Herpes simplex virus (HSV) is an important human pathogen. It enters cells through an orchestrated process that requires four essential glycoproteins, gD, gH/gL, and gB, activated in cascade fashion by receptor-binding and signaling. gH/gL heterodimer is conserved across the Herpesviridae family. HSV entry is enabled by gH/gL interaction with alphavbeta6- or alphavbeta8-integrin receptors. We report that the interaction of virion gH/gL with integrins resulted in gL dissociation and its release in the medium. gL dissociation occurred if all components of the entry apparatus-receptor-bound gD and gB-were present and was prevented if entry was blocked by a neutralizing monoclonal antibody to gH or by a mutation in gH. We propose that (i) gL dissociation from gH/gL is part of the activation of HSV glycoproteins, critical for HSV entry; and (ii) gL is a functional inhibitor of gH and maintains gH in an inhibited form until receptor bound gD and integrins signal to gH/gL. PMID- 26157135 TI - Resolving cryptic aspects of cryptochrome signaling. PMID- 26157136 TI - Suppression of conformational heterogeneity at a protein-protein interface. AB - Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium's evasion of the host immune system. SpA includes five small three-helix-bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the Fc fragment of IgG was partially elucidated previously in the crystal structure 1FC2. Although informative, the previous structure was not properly folded and left many substantial questions unanswered, such as a detailed description of the tertiary structure of SpA domains in complex with Fc and the structural changes that take place upon binding. Here we report the 2.3-A structure of a fully folded SpA domain in complex with Fc. Our structure indicates that there are extensive structural rearrangements necessary for binding Fc, including a general reduction in SpA conformational heterogeneity, freezing out of polyrotameric interfacial residues, and displacement of a SpA side chain by an Fc side chain in a molecular-recognition pocket. Such a loss of conformational heterogeneity upon formation of the protein protein interface may occur when SpA binds its multiple binding partners. Suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins. PMID- 26157137 TI - Rectifying disordered brain dynamics to improve cognition in schizophrenia. PMID- 26157138 TI - Myosin light chain phosphorylation to the rescue. PMID- 26157139 TI - Filamin A is required in injured axons for HDAC5 activity and axon regeneration. AB - Microtubule dynamics are important for axon growth during development as well as axon regeneration after injury. We have previously identified HDAC5 as an injury regulated tubulin deacetylase that functions at the injury site to promote axon regeneration. However, the mechanisms involved in the spatial control of HDAC5 activity remain poorly understood. Here we reveal that HDAC5 interacts with the actin binding protein filamin A via its C-terminal domain. Filamin A plays critical roles in HDAC5-dependent tubulin deacetylation because, in cells lacking filamin A, the levels of acetylated tubulin are elevated markedly. We found that nerve injury increases filamin A axonal expression in a protein synthesis dependent manner. Reducing filamin A levels or interfering with the interaction between HDAC5 and filamin A prevents injury-induced tubulin deacetylation as well as HDAC5 localization at the injured axon tips. In addition, neurons lacking filamin A display reduced axon regeneration. Our findings suggest a model in which filamin A local translation following axon injury controls localized HDAC5 activity to promote axon regeneration. PMID- 26157140 TI - Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation. AB - Pituitary adenylate cyclase-activating peptide (PACAP) is a neurotrophic peptide involved in a wide range of nervous functions, including development, differentiation, and survival, and various aspects of learning and memory. Here we report that PACAP induces the expression of regulator of calcineurin 1 (RCAN1, also known as DSCR1), which is abnormally expressed in the brains of Down syndrome patients. Increased RCAN1 expression is accompanied by activation of the PKA-cAMP response element-binding protein pathways. EMSA and ChIP analyses demonstrate the presence of a functional cAMP response element in the RCAN1 promoter. Moreover, we show that PACAP-dependent neuronal differentiation is significantly disturbed by improper RCAN1 expression. Our data provide the first evidence of RCAN1, a Down syndrome-related gene, as a novel target for control of the neurotrophic function of PACAP. PMID- 26157141 TI - Mitochondrial Respiratory Dysfunction Induces Claudin-1 Expression via Reactive Oxygen Species-mediated Heat Shock Factor 1 Activation, Leading to Hepatoma Cell Invasiveness. AB - Although mitochondrial dysfunction has been implicated in tumor metastasis, it is unclear how it regulates tumor cell aggressiveness. We have reported previously that human hepatoma cells harboring mitochondrial defects have high tumor cell invasion activity via increased claudin-1 (Cln-1) expression. In this study, we demonstrated that mitochondrial respiratory defects induced Cln-1 transcription via reactive oxygen species (ROS)-mediated heat shock factor 1 (HSF1) activation, which contributed to hepatoma invasiveness. We first confirmed the inverse relationship between mitochondrial defects and Cln-1 induction in SNU hepatoma cells and hepatocellular carcinoma tissues. We then examined five different respiratory complex inhibitors, and complex I inhibition by rotenone most effectively induced Cln-1 at the transcriptional level. Rotenone increased both mitochondrial and cytosolic ROS. In addition, rotenone-induced Cln-1 expression was attenuated by N-acetylcysteine, an antioxidant, and exogenous H2O2 treatment was enough to increase Cln-1 transcription, implying the involvement of ROS. Next we found that ROS-mediated HSF1 activation via hyperphosphorylation was the key event for Cln-1 transcription. Moreover, the Cln-1 promoter region (from -529 to +53) possesses several HSF1 binding elements, and this region showed increased promoter activity and HSF1 binding affinity in response to rotenone treatment. Finally, we demonstrated that the invasion activity of SNU449 cells, which harbor mitochondrial defects, was blocked by siRNA-mediated HSF1 knockdown. Taken together, these results indicate that mitochondrial respiratory defects enhance Cln-1-mediated hepatoma cell invasiveness via mitochondrial ROS-mediated HSF1 activation, presenting a potential role for HSF1 as a novel mitochondrial retrograde signal-responsive transcription factor to control hepatoma cell invasiveness. PMID- 26157142 TI - JmjC Domain-containing Protein 6 (Jmjd6) Derepresses the Transcriptional Repressor Transcription Factor 7-like 1 (Tcf7l1) and Is Required for Body Axis Patterning during Xenopus Embryogenesis. AB - Tcf7l1 (also known as Tcf3) is a bimodal transcription factor that plays essential roles in embryogenesis and embryonic and adult stem cells. On one hand, Tcf7l1 works as transcriptional repressor via the recruitment of Groucho-related transcriptional corepressors to repress the transcription of Wnt target genes, and, on the other hand, it activates Wnt target genes when Wnt-activated beta catenin interacts with it. However, how its activity is modulated is not well understood. Here we demonstrate that a JmjC-domain containing protein, Jmjd6, interacts with Tcf7l and derepresses Tcf7l. We show that Jmjd6 binds to a region of Tcf7l1 that is also responsible for Groucho interaction, therefore making it possible that Jmjd6 binding displaces the Groucho transcriptional corepressor from Tcf7l1. Moreover, we show that Jmjd6 antagonizes the repression effect of Tcf7l1 on target gene transcription and is able to enhance beta-catenin-induced gene activation and that, vice versa, inhibition of Jmjd6 activity compromises gene activation in both cells and Xenopus early embryos. We also show that jmjd6 is both maternally and zygotically transcribed during Xenopus embryogenesis. Loss of Jmjd6 function causes defects in anterioposterior body axis formation and down regulation of genes that are involved in anterioposterior axis patterning. The results elucidate a novel mechanism underlying the regulation of Tcf7l1 activity and the regulation of embryonic body axis formation. PMID- 26157143 TI - Phosphatidylinositol-4-phosphate 5-Kinase 1alpha Modulates Ribosomal RNA Gene Silencing through Its Interaction with Histone H3 Lysine 9 Trimethylation and Heterochromatin Protein HP1-alpha. AB - Phosphoinositide signaling has been implicated in the regulation of numerous cellular processes including cytoskeletal dynamics, cellular motility, vesicle trafficking, and gene transcription. Studies have also shown that nuclear phosphoinositide(s) regulates processes such as mRNA export, cell cycle progression, gene transcription, and DNA repair. We have shown previously that the nuclear form of phosphatidylinositol-4-phosphate 5-kinase 1alpha (PIP5K), the enzyme responsible for phosphatidylinositol 4,5-bisphosphate synthesis, is modified by small ubiquitin-like modifier (SUMO)-1. In this study, we have shown that due to the site-specific Lys to Ala mutations of PIP5K at Lys-244 and Lys 490, it is unable to localize in the nucleus and nucleolus, respectively. Furthermore, by using chromatin immunoprecipitation assays, we have observed that PIP5K associates with the chromatin silencing complex constituted of H3K9me3 and heterochromatin protein 1alpha at multiple ribosomal DNA (rDNA) loci. These interactions followed a definite cyclical pattern of occupancy (mostly G1) and release from the rDNA loci (G1/S) throughout the cell cycle. Moreover, the immunoprecipitation results clearly demonstrate that PIP5K SUMOylated at Lys-490 interacts with components of the chromatin silencing machinery, H3K9me3 and heterochromatin protein 1alpha. However, PIP5K does not interact with the gene activation signature protein H3K4me3. This study, for the first time, demonstrates that PIP5K, an enzyme actively associated with lipid modification pathway, has additional roles in rDNA silencing. PMID- 26157144 TI - The Orphan Nuclear Receptor NR4A1 Protects Pancreatic beta-Cells from Endoplasmic Reticulum (ER) Stress-mediated Apoptosis. AB - The role of NR4A1 in apoptosis is controversial. Pancreatic beta-cells often face endoplasmic reticulum (ER) stress under adverse conditions such as high free fatty acid (FFA) concentrations and sustained hyperglycemia. Severe ER stress results in beta-cell apoptosis. The aim of this study was to analyze the role of NR4A1 in ER stress-mediated beta-cell apoptosis and to characterize the related mechanisms. We confirmed that upon treatment with the ER stress inducers thapsigargin (TG) or palmitic acid (PA), the mRNA and protein levels of NR4A1 rapidly increased in both MIN6 cells and mouse islets. NR4A1 overexpression in MIN6 cells conferred resistance to cell loss induced by TG or PA, as assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and TUNEL assays indicated that NR4A1 overexpression also protected against ER stress induced apoptosis. This conclusion was further confirmed by experiments exploiting siRNA to knockdown NR4A1 expression in MIN6 cells or exploiting NR4A1 knock-out mice. NR4A1 overexpression in MIN6 cells reduced C/EBP homologous protein (CHOP) expression and Caspase3 activation induced by TG or PA. NR4A1 overexpression in MIN6 cells or mouse islets resulted in Survivin up-regulation. A critical regulatory element was identified in Survivin promoter (-1872 bp to 1866 bp) with a putative NR4A1 binding site; ChIP assays demonstrated that NR4A1 physically associates with the Survivin promoter. In conclusion, NR4A1 protects pancreatic beta-cells against ER stress-mediated apoptosis by up-regulating Survivin expression and down-regulating CHOP expression, which we termed as "positive and negative regulation." PMID- 26157145 TI - beta-Arrestin Recruitment and Biased Agonism at Free Fatty Acid Receptor 1. AB - FFAR1/GPR40 is a seven-transmembrane domain receptor (7TMR) expressed in pancreatic beta cells and activated by FFAs. Pharmacological activation of GPR40 is a strategy under consideration to increase insulin secretion in type 2 diabetes. GPR40 is known to signal predominantly via the heterotrimeric G proteins Gq/11. However, 7TMRs can also activate functionally distinct G protein independent signaling via beta-arrestins. Further, G protein- and beta-arrestin based signaling can be differentially modulated by different ligands, thus eliciting ligand-specific responses ("biased agonism"). Whether GPR40 engages beta-arrestin-dependent mechanisms and is subject to biased agonism is unknown. Using bioluminescence resonance energy transfer-based biosensors for real-time monitoring of cell signaling in living cells, we detected a ligand-induced GPR40 beta-arrestin interaction, with the synthetic GPR40 agonist TAK-875 being more effective than palmitate or oleate in recruiting beta-arrestins 1 and 2. Conversely, TAK-875 acted as a partial agonist of Gq/11-dependent GPR40 signaling relative to both FFAs. Pharmacological blockade of Gq activity decreased FFA induced insulin secretion. In contrast, knockdown or genetic ablation of beta arrestin 2 in an insulin-secreting cell line and mouse pancreatic islets, respectively, uniquely attenuated the insulinotropic activity of TAK-875, thus providing functional validation of the biosensor data. Collectively, these data reveal that in addition to coupling to Gq/11, GPR40 is functionally linked to a beta-arrestin 2-mediated insulinotropic signaling axis. These observations expose previously unrecognized complexity for GPR40 signal transduction and may guide the development of biased agonists showing improved clinical profile in type 2 diabetes. PMID- 26157146 TI - Cytochrome P450 3A Enzymes Catalyze the O6-Demethylation of Thebaine, a Key Step in Endogenous Mammalian Morphine Biosynthesis. AB - Morphine, first characterized in opium from the poppy Papaver somniferum, is one of the strongest known analgesics. Endogenous morphine has been identified in several mammalian cells and tissues. The synthetic pathway of morphine in the opium poppy has been elucidated. The presence of common intermediates in plants and mammals suggests that biosynthesis occurs through similar pathways (beginning with the amino acid L-tyrosine), and the pathway has been completely delineated in plants. Some of the enzymes in the mammalian pathway have been identified and characterized. Two of the latter steps in the morphine biosynthesis pathway are demethylation of thebaine at the O(3)- and the O(6)-positions, the latter of which has been difficult to demonstrate. The plant enzymes responsible for both the O(3)-demethylation and the O(6)-demethylation are members of the Fe(II)/alpha ketoglutarate-dependent dioxygenase family. Previous studies showed that human cytochrome P450 (P450) 2D6 can catalyze thebaine O(3)-demethylation. We report that demethylation of thebaine at the O(6)-position is selectively catalyzed by human P450s 3A4 and 3A5, with the latter being more efficient, and rat P450 3A2. Our results do not support O(6)-demethylation of thebaine by an Fe(II)/alpha ketoglutarate-dependent dioxygenase. In rat brain microsomes, O(6)-demethylation was inhibited by ketoconazole, but not sulfaphenazole, suggesting that P450 3A enzymes are responsible for this activity in the brain. An alternate pathway to morphine, oripavine O(6)-demethylation, was not detected. The major enzymatic steps in mammalian morphine synthesis have now been identified. PMID- 26157147 TI - New tumour antigen PLAC1/CP1, a potentially useful prognostic marker and immunotherapy target for gastric adenocarcinoma. AB - AIM: To evaluate protein expression and clinical significance of PLAC1/CP1 antigen in primary gastric adenocarcinoma. METHODS: Protein expression of PLAC1/CP1 was analysed by tissue chip and immunohistochemistry in surgical specimens obtained from 119 patients with gastric cancer. The data were analysed using SPSS V.16.0 software applying the chi(2) test and Kaplan-Meier method. RESULTS: The positive expression frequency of PLAC1/CP1 protein was 61.3% (73/119 patients). The overall survival of patients with PLAC1/CP1 protein-positive expression was significantly lower than that of patients with PLAC1/CP1 protein negative expression (p<0.05). There was no significant relationship between PLAC1/CP1 expression and patient gender, age, tumour position, tumour size, differentiation, gross type, lymph node or TNM stage. CONCLUSIONS: PLAC1/CP1 protein is expressed in over half of cases of primary gastric cancer, and PLAC1/CP1 protein expression is inversely correlated with patient survival. The data indicate that PLAC1/CP1 provides a marker for identifying gastric cancers with poor prognosis, and suggest that PLAC1/CP1 may provide a useful target for immunotherapy. PMID- 26157148 TI - Comparison of FilmArray and Quantitative Real-Time Reverse Transcriptase PCR for Detection of Zaire Ebolavirus from Contrived and Clinical Specimens. AB - Rapid, reliable, and easy-to-use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are urgently needed. The goal of this study was to examine the agreement among emergency use authorization (EUA) tests for the detection of ZEBOV nucleic acids, including the BioFire FilmArray BioThreat (BT) panel, the FilmArray BT-E panel, and the NP2 and VP40 quantitative real-time reverse transcriptase (qRT) PCR assays from the Centers for Disease Control and Prevention (CDC). Specimens used in this study included whole blood spiked with inactivated ZEBOV at known titers and whole-blood, plasma, and urine clinical specimens collected from persons diagnosed with Ebola virus disease (EVD). The agreement for FilmArray and qRT-PCR results using contrived whole-blood specimens was 100% (6/6 specimens) for each ZEBOV dilution from 4 * 10(7) to 4 * 10(2) 50% tissue culture infective dose (TCID50)/ml, as well as the no-virus negative control sample. The limit of detection for FilmArray and qRT-PCR assays with inactivated ZEBOV, based on duplicate positive results, was determined to be 4 * 10(2) TCID50/ml. Rates of agreement between FilmArray and qRT-PCR results for clinical specimens from patients with EVD were 85% (23/27 specimens) for whole blood specimens, 90% (18/20 specimens) for whole-blood specimens tested by FilmArray testing and matched plasma specimens tested by qRT-PCR testing, and 85% (11/13 specimens) for urine specimens. Among 60 specimens, eight discordant results were noted, with ZEBOV nucleic acids being detected only by FilmArray testing in four specimens and only by qRT-PCR testing in the remaining four specimens. These findings demonstrate that the rapid and easy-to-use FilmArray panels are effective tests for evaluating patients with EVD. PMID- 26157149 TI - Support from Phylogenomic Networks and Subspecies Signatures for Separation of Mycobacterium massiliense from Mycobacterium bolletii. AB - Mycobacterium abscessus subspecies classification has important clinical implications. We used phylogenomic network and amino acid analyses to provide evidence for the separation of Mycobacterium bolletii and Mycobacterium massiliense into two distinct subspecies which can potentially be differentiated rapidly by their protein signatures. PMID- 26157150 TI - Infectious Middle East Respiratory Syndrome Coronavirus Excretion and Serotype Variability Based on Live Virus Isolates from Patients in Saudi Arabia. AB - The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 1,082 people, including 439 fatalities. So far, no empirical virus isolation study has been done to elucidate infectious virus secretion or serotype variability. Here, we used 51 respiratory samples from 32 patients with confirmed MERS-CoV infection for virus isolation in Vero B4 and Caco-2 cells. We found Caco-2 cells to significantly enhance isolation success over routinely used Vero cells. Isolation success correlated with viral RNA concentration and time after diagnosis as well as with the amount of IgA antibodies secreted in respiratory samples used for isolation. Results from plaque reduction neutralization assays using a representative range of serum samples and virus isolates suggested that all circulating human MERS-CoV strains represent one single serotype. The choice of prototype strain is not likely to influence the success of candidate MERS-CoV vaccines. However, vaccine formulations should be evaluated for their potential to induce IgA. PMID- 26157151 TI - Case-Control Study of Risk Factors for Sporadic Giardiasis and Parasite Assemblages in North West England. AB - Giardia duodenalis is a major cause of infectious gastroenteritis worldwide, and it is diversified into eight genetic assemblages (A to H), which are distinguishable only by molecular typing. There is some evidence that the assemblages infecting humans (assemblages A and B) may have different transmission routes, but systematically acquired data, combining epidemiological and molecular findings, are required. We undertook a case-control study with Giardia genotyping in North West England, to determine general and parasite assemblage-specific risk factors. For people without a history of foreign travel, swimming in swimming pools and changing diapers were the most important risk factors for the disease. People infected with assemblage B reported a greater number of symptoms and higher frequencies of vomiting, abdominal pain, swollen stomach, and loss of appetite, compared with people infected with assemblage A. More importantly, keeping a dog was associated only with assemblage A infections, suggesting the presence of a potential zoonotic reservoir for this assemblage. This is the first case-control study to combine epidemiological data with Giardia genotyping, and it shows the importance of integrating these two levels of information for better understanding of the epidemiology of this pathogen. PMID- 26157152 TI - Multilocus Sequence Analysis of Clinical "Candidatus Neoehrlichia mikurensis" Strains from Europe. AB - "Candidatus Neoehrlichia mikurensis" is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of "Ca. Neoehrlichia" has been studied only by comparing 16S rRNA genes and groEL operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical "Ca. Neoehrlichia" strains in Europe and their relatedness to other species within the Anaplasmataceae family. Six genes were selected: ftsZ, clpB, gatB, lipA, groEL, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed "Ca. Neoehrlichia" infection from Sweden (n = 9), the Czech Republic (n = 2), and Germany (n = 1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA, ftsZ, gatB, and groEL. According to the MLSA, among the Anaplasmataceae, "Ca. Neoehrlichia" is most closely related to Ehrlichia ruminantium, less so to Anaplasma phagocytophilum, and least to Wolbachia endosymbionts. To conclude, three sequence types of infectious "Ca. Neoehrlichia" were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe. PMID- 26157153 TI - Humicola sp. as a Cause of Peritoneal Dialysis-Associated Peritonitis. AB - Peritoneal dialysis is the renal replacement modality used by ~20% of patients with end-stage kidney disease (S. McDonald, P. Clayton, and K. Hurst, p. 6.2 6.27, in ANZDATA 2012 Annual Report, 35th ed., 2012). A major complication of peritoneal dialysis is the development of peritonitis. We describe a case of Humicola sp. causing peritoneal dialysis (PD)-associated peritonitis, successfully treated with a prolonged course of antifungal therapy. PMID- 26157154 TI - Characterization of a Clone of Mycobacterium tuberculosis Clinical Isolates with Mutations in KatG (A110V), EthA (Q269STOP), and the inhA Promoter (-15C->T). PMID- 26157156 TI - Correction for Thobakgale et al., Impact of HLA in Mother and Child on Disease Progression of Pediatric Human Immunodeficiency Virus Type 1 Infection. PMID- 26157158 TI - Water loss in tree weta (Hemideina): adaptation to the montane environment and a test of the melanisation-desiccation resistance hypothesis. AB - Montane insects are at a higher risk of desiccation than their lowland counterparts and are expected to have evolved reduced water loss. Hemideina spp. (tree weta; Orthoptera: Anostostomatidae) have both lowland (Hemideina femorata, Hemideina crassidens and Hemideina thoracica) and montane (Hemideina maori and Hemideina ricta) species. H. maori has both melanic and yellow morphs. We use these weta to test two hypotheses: that montane insects lose water more slowly than lowland species, and that cuticular water loss rates are lower in darker insects than lighter morphs, because of incorporation of melanin in the cuticle. We used flow-through respirometry to compare water loss rates among Hemideina species and found that montane weta have reduced cuticular water loss by 45%, reduced respiratory water loss by 55% and reduced the molar ratio of VH2 O:VCO2 by 64% compared with lowland species. Within H. maori, cuticular water loss was reduced by 46% when compared with yellow morphs. Removal of cuticular hydrocarbons significantly increased total water loss in both melanic and yellow morphs, highlighting the role that cuticular hydrocarbons play in limiting water loss; however, the dark morph still lost water more slowly after removal of cuticular hydrocarbons (57% less), supporting the melanisation-desiccation resistance hypothesis. PMID- 26157159 TI - Lung mechanics and pulmonary function testing in cetaceans. AB - We measured esophageal pressures, respiratory flow rates, and expired O2 and CO2 in six adult bottlenose dolphins (Tursiops truncatus) during voluntary breaths and maximal (chuff) respiratory efforts. The data were used to estimate the dynamic specific lung compliance (sCL), the O2 consumption rate (VO2 ) and CO2 production rates (VCO2 ) during rest. Our results indicate that bottlenose dolphins have the capacity to generate respiratory flow rates that exceed 130 l s(-1) and 30 l s(-1) during expiration and inspiration, respectively. The esophageal pressures indicated that expiration is passive during voluntary breaths, but active during maximal efforts, whereas inspiration is active for all breaths. The average sCL of dolphins was 0.31+/-0.04 cmH2O(-1), which is considerably higher than that of humans (0.08 cmH2O(-1)) and that previously measured in a pilot whale (0.13 cmH2O(-1)). The average estimated VO2 and VCO2 using our breath-by-breath respirometry system ranged from 0.857 to 1.185 l O2 min(-1) and 0.589 to 0.851 l CO2 min(-1), respectively, which is similar to previously published metabolic measurements from the same animals using conventional flow-through respirometry. In addition, our custom-made system allows us to approximate end tidal gas composition. Our measurements provide novel data for respiratory physiology in cetaceans, which may be important for clinical medicine and conservation efforts. PMID- 26157160 TI - Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation. AB - Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. PMID- 26157161 TI - Eye movements in chameleons are not truly independent - evidence from simultaneous monocular tracking of two targets. AB - Chameleons perform large-amplitude eye movements that are frequently referred to as independent, or disconjugate. When prey (an insect) is detected, the chameleon's eyes converge to view it binocularly and 'lock' in their sockets so that subsequent visual tracking is by head movements. However, the extent of the eyes' independence is unclear. For example, can a chameleon visually track two small targets simultaneously and monocularly, i.e. one with each eye? This is of special interest because eye movements in ectotherms and birds are frequently independent, with optic nerves that are fully decussated and intertectal connections that are not as developed as in mammals. Here, we demonstrate that chameleons presented with two small targets moving in opposite directions can perform simultaneous, smooth, monocular, visual tracking. To our knowledge, this is the first demonstration of such a capacity. The fine patterns of the eye movements in monocular tracking were composed of alternating, longer, 'smooth' phases and abrupt 'step' events, similar to smooth pursuits and saccades. Monocular tracking differed significantly from binocular tracking with respect to both 'smooth' phases and 'step' events. We suggest that in chameleons, eye movements are not simply 'independent'. Rather, at the gross level, eye movements are (i) disconjugate during scanning, (ii) conjugate during binocular tracking and (iii) disconjugate, but coordinated, during monocular tracking. At the fine level, eye movements are disconjugate in all cases. These results support the view that in vertebrates, basic monocular control is under a higher level of regulation that dictates the eyes' level of coordination according to context. PMID- 26157162 TI - Ipl1/Aurora-B is necessary for kinetochore restructuring in meiosis I in Saccharomyces cerevisiae. AB - In mitosis, the centromeres of sister chromosomes are pulled toward opposite poles of the spindle. In meiosis I, the opposite is true: the sister centromeres move together to the same pole, and the homologous chromosomes are pulled apart. This change in segregation patterns demands that between the final mitosis preceding meiosis and the first meiotic division, the kinetochores must be restructured. In budding yeast, unlike mammals, kinetochores are largely stable throughout the mitotic cycle. In contrast, previous work with budding and fission yeast showed that some outer kinetochore proteins are lost in early meiosis. We use quantitative mass spectrometry methods and imaging approaches to explore the kinetochore restructuring process that occurs in meiosis I in budding yeast. The Ndc80 outer kinetochore complex, but not other subcomplexes, is shed upon meiotic entry. This shedding is regulated by the conserved protein kinase Ipl1/Aurora-B and promotes the subsequent assembly of a kinetochore that will confer meiosis specific segregation patterns on the chromosome. PMID- 26157163 TI - Regulation of TGF-beta receptor hetero-oligomerization and signaling by endoglin. AB - Complex formation among transforming growth factor-beta (TGF-beta) receptors and its modulation by coreceptors represent an important level of regulation for TGF beta signaling. Oligomerization of ALK5 and the type II TGF-beta receptor (TbetaRII) has been thoroughly investigated, both in vitro and in intact cells. However, such studies, especially in live cells, are missing for the endothelial cell coreceptor endoglin and for the ALK1 type I receptor, which enables endothelial cells to respond to TGF-beta by activation of both Smad2/3 and Smad1/5/8. Here we combined immunoglobulin G-mediated immobilization of one cell surface receptor with lateral mobility studies of a coexpressed receptor by fluorescence recovery after photobleaching (FRAP) to demonstrate that endoglin forms stable homodimers that function as a scaffold for binding TbetaRII, ALK5, and ALK1. ALK1 and ALK5 bind to endoglin with differential dependence on TbetaRII, which plays a major role in recruiting ALK5 to the complex. Signaling data indicate a role for the quaternary receptor complex in regulating the balance between TGF-beta signaling to Smad1/5/8 and to Smad2/3. PMID- 26157164 TI - Actin remodeling by Nck regulates endothelial lumen formation. AB - Multiple angiogenic cues modulate phosphotyrosine signaling to promote vasculogenesis and angiogenesis. Despite its functional and clinical importance, how vascular cells integrate phosphotyrosine-dependent signaling to elicit cytoskeletal changes required for endothelial morphogenesis remains poorly understood. The family of Nck adaptors couples phosphotyrosine signals with actin dynamics and therefore is well positioned to orchestrate cellular processes required in vascular formation and remodeling. Culture of endothelial cells in three-dimensional collagen matrices in the presence of VEGF stimulation was combined with molecular genetics, optical imaging, and biochemistry to show that Nck-dependent actin remodeling promotes endothelial cell elongation and proper organization of VE-cadherin intercellular junctions. Major morphogenetic defects caused by abrogation of Nck signaling included loss of endothelial apical-basal polarity and impaired lumenization. Time-lapse imaging using a Forster resonance energy transfer biosensor, immunostaining with phospho-specific antibodies, and GST pull-down assays showed that Nck determines spatiotemporal patterns of Cdc42/aPKC activation during endothelial morphogenesis. Our results demonstrate that Nck acts as an important hub integrating angiogenic cues with cytoskeletal changes that enable endothelial apical-basal polarization and lumen formation. These findings point to Nck as an emergent target for effective antiangiogenic therapy. PMID- 26157165 TI - Disassembly activity of actin-depolymerizing factor (ADF) is associated with distinct cellular processes in apicomplexan parasites. AB - Proteins of the actin-depolymerizing factor (ADF)/cofilin family have been shown to be crucial for the motility and survival of apicomplexan parasites. However, the mechanisms by which ADF proteins fulfill their function remain poorly understood. In this study, we investigate the comparative activities of ADF proteins from Toxoplasma gondii and Plasmodium falciparum, the human malaria parasite, using a conditional T. gondii ADF-knockout line complemented with ADF variants from either species. We show that P. falciparum ADF1 can fully restore native TgADF activity, demonstrating functional conservation between parasites. Strikingly, mutation of a key basic residue (Lys-72), previously implicated in disassembly in PfADF1, had no detectable phenotypic effect on parasite growth, motility, or development. In contrast, organelle segregation was severely impaired when complementing with a TgADF mutant lacking the corresponding residue (Lys-68). Biochemical analyses of each ADF protein confirmed the reduced ability of lysine mutants to mediate actin depolymerization via filament disassembly although not severing, in contrast to previous reports. These data suggest that actin filament disassembly is essential for apicomplexan parasite development but not for motility, as well as pointing to genus-specific coevolution between ADF proteins and their native actin. PMID- 26157167 TI - Interferon-gamma-inducible Rab20 regulates endosomal morphology and EGFR degradation in macrophages. AB - Little is known about the molecular players that regulate changes in the endocytic pathway during immune activation. Here we investigate the role of Rab20 in the endocytic pathway during activation of macrophages. Rab20 is associated with endocytic structures, but the function of this Rab GTPase in the endocytic pathway remains poorly characterized. We find that in macrophages, Rab20 expression and endosomal association significantly increase after interferon gamma (IFN-gamma) treatment. Moreover, IFN-gamma and Rab20 expression induce a dramatic enlargement of endosomes. These enlarged endosomes are the result of homotypic fusion promoted by Rab20 expression. The expression of Rab20 or the dominant-negative mutant Rab20T19N does not affect transferrin or dextran 70 kDa uptake. However, knockdown of Rab20 accelerates epidermal growth factor (EGF) trafficking to LAMP-2-positive compartments and EGF receptor degradation. Thus this work defines a function for Rab20 in the endocytic pathway during immune activation of macrophages. PMID- 26157166 TI - Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport. AB - The importance of endosome-to-trans-Golgi network (TGN) retrograde transport in the anterograde transport of proteins is unclear. In this study, genome-wide screening of the factors necessary for efficient anterograde protein transport in human haploid cells identified subunits of the Golgi-associated retrograde protein (GARP) complex, a tethering factor involved in endosome-to-TGN transport. Knockout (KO) of each of the four GARP subunits, VPS51-VPS54, in HEK293 cells caused severely defective anterograde transport of both glycosylphosphatidylinositol (GPI)-anchored and transmembrane proteins from the TGN. Overexpression of VAMP4, v-SNARE, in VPS54-KO cells partially restored not only endosome-to-TGN retrograde transport, but also anterograde transport of both GPI-anchored and transmembrane proteins. Further screening for genes whose overexpression normalized the VPS54-KO phenotype identified TMEM87A, encoding an uncharacterized Golgi-resident membrane protein. Overexpression of TMEM87A or its close homologue TMEM87B in VPS54-KO cells partially restored endosome-to-TGN retrograde transport and anterograde transport. Therefore GARP- and VAMP4 dependent endosome-to-TGN retrograde transport is required for recycling of molecules critical for efficient post-Golgi anterograde transport of cell-surface integral membrane proteins. In addition, TMEM87A and TMEM87B are involved in endosome-to-TGN retrograde transport. PMID- 26157168 TI - Coupling between cytoplasmic concentration gradients through local control of protein mobility in the Caenorhabditis elegans zygote. AB - Cell polarity is characterized by the asymmetric distribution of factors at the cell cortex and in the cytoplasm. Although mechanisms that establish cortical asymmetries have been characterized, less is known about how persistent cytoplasmic asymmetries are generated. During the asymmetric division of the Caenorhabditis elegans zygote, the PAR proteins orchestrate the segregation of the cytoplasmic RNA-binding proteins MEX-5/6 to the anterior cytoplasm and PIE-1, POS-1, and MEX-1 to the posterior cytoplasm. In this study, we find that MEX-5/6 control the segregation of GFP::PIE-1, GFP::POS-1, and GFP::MEX-1 by locally increasing their mobility in the anterior cytoplasm. Remarkably, PIE-1, POS-1, and MEX-1 form gradients with distinct strengths, which correlates with differences in their responsiveness to MEX-5/6. We show that MEX-5/6 act downstream of the polarity regulators PAR-1 and PAR-3 and in a concentration dependent manner to increase the mobility of GFP::PIE-1. These findings suggest that the MEX-5/6 concentration gradients are directly coupled to the establishment of posterior-rich PIE-1, POS-1, and MEX-1 concentration gradients via the formation of anterior-fast, posterior-slow mobility gradients. PMID- 26157170 TI - Variation of floret fertility in hexaploid wheat revealed by tiller removal. AB - Grain number per spike, which is greatly influenced by floret fertility, is an important trait of wheat (Triticum aestivum L.) yield. Maximum floret primordia, fertile floret, and final grain number per spikelet are three crucial factors of floret fertility. Floral degradation plays a critical role in determining these three floret fertility-related traits. Twelve hexaploid spring wheat genotypes were selected to investigate the influence of detillering on floral degradation and floret fertility-related traits in the field and greenhouse. Notably, the green anther stage was found to consistently have the maximum floret primordia number. Visible floral degradation, however, was observed to occur at several floral developmental stages, specifically from green anther stage to anthesis. Detillering was able to delay floral degradation in most cases and was evidently highly associated with increased maximum floret primordia, fertile floret, and final grain number per spikelet, with only a few exceptions. Thermal time required for each floral developmental stage was overall not influenced by detillering. These data hereby reveal a predominant spikelet fertility pattern along the spike in which the number of fertile florets per spikelet at anthesis becomes developmentally confined. PMID- 26157169 TI - Cardiolipin's propensity for phase transition and its reorganization by dynamin related protein 1 form a basis for mitochondrial membrane fission. AB - Cardiolipin (CL) is an atypical, dimeric phospholipid essential for mitochondrial dynamics in eukaryotic cells. Dynamin-related protein 1 (Drp1), a cytosolic member of the dynamin superfamily of large GTPases, interacts with CL and functions to sustain the balance of mitochondrial division and fusion by catalyzing mitochondrial fission. Although recent studies have indicated a role for CL in stimulating Drp1 self-assembly and GTPase activity at the membrane surface, the mechanism by which CL functions in membrane fission, if at all, remains unclear. Here, using a variety of fluorescence spectroscopic and imaging approaches together with model membranes, we demonstrate that Drp1 and CL function cooperatively in effecting membrane constriction toward fission in three distinct steps. These involve 1) the preferential association of Drp1 with CL localized at a high spatial density in the membrane bilayer, 2) the reorganization of unconstrained, fluid-phase CL molecules in concert with Drp1 self-assembly, and 3) the increased propensity of CL to transition from a lamellar, bilayer arrangement to an inverted hexagonal, nonbilayer configuration in the presence of Drp1 and GTP, resulting in the creation of localized membrane constrictions that are primed for fission. Thus we propose that Drp1 and CL function in concert to catalyze mitochondrial division. PMID- 26157171 TI - IL-1 Receptor Antagonist Chimeric Protein: Context-Specific and Inflammation Restricted Activation. AB - Both IL-1alpha and IL-1beta are highly inflammatory cytokines mediating a wide spectrum of diseases. A recombinant form of the naturally occurring IL-1R antagonist (IL-1Ra), which blocks IL-1R1, is broadly used to treat autoimmune and autoinflammatory diseases; however, blocking IL-1 increases the risk of infection. In this study, we describe the development of a novel form of recombinant IL-1Ra, termed chimeric IL-1Ra. This molecule is a fusion of the N terminal peptide of IL-1beta and IL-1Ra, resulting in inactive IL-1Ra. Because the IL-1beta N-terminal peptide contains several protease sites clustered around the caspase-1 site, local proteases at sites of inflammation can cleave chimeric IL-1Ra and turn IL-1Ra active. We demonstrate that chimeric IL-1Ra reduces IL-1 mediated inflammation in vitro and in vivo. This unique approach limits IL-1 receptor blockade to sites of inflammation, while sparing a multitude of desired IL-1-related activities, including host defense against infections and IL-1 mediated repair. PMID- 26157172 TI - Processing of CD74 by the Intramembrane Protease SPPL2a Is Critical for B Cell Receptor Signaling in Transitional B Cells. AB - The invariant chain (CD74), a chaperone in MHC class II-mediated Ag presentation, is sequentially processed by different endosomal proteases. We reported recently that clearance of the final membrane-bound N-terminal fragment (NTF) of CD74 is mediated by the intramembrane protease signal peptide peptidase-like (SPPL)2a, a process critical for B cell development. In mice, SPPL2a deficiency provokes the accumulation of this NTF in endocytic vesicles, which leads to a B cell maturation arrest at the transitional 1 stage. To define the underlying mechanism, we analyzed the impact of SPPL2a deficiency on signaling pathways involved in B cell homeostasis. We demonstrate that tonic as well as BCR-induced activation of the PI3K/Akt pathway is massively compromised in SPPL2a(-/-) B cells and identify this as major cause of the B cell maturation defect in these mice. Altered BCR trafficking induces a reduction of surface IgM in SPPL2a deficient B cells, leading to a diminished signal transmission via the BCR and the tyrosine kinase Syk. We provide evidence that in SPPL2a(-/-) mice impaired BCR signaling is to a great extent provoked by the accumulating CD74 NTF, which can interact with the BCR and Syk, and that impaired PI3K/Akt signaling and reduced surface IgM are not directly linked processes. In line with disturbances in PI3K/Akt signaling, SPPL2a(-/-) B cells show a dysregulation of the transcription factor FOXO1, causing elevated transcription of proapoptotic genes. We conclude that SPPL2a-mediated processing of CD74 NTF is indispensable to maintain appropriate levels of tonic BCR signaling to promote B cell maturation. PMID- 26157173 TI - A Subset of CD8alphabeta+ Invariant NKT Cells in a Humanized Mouse Model. AB - Invariant NKT (iNKT) cells are unconventional innate-like T cells demonstrating potent antitumor function in conventional mouse models. However, the iNKT cell ligands have had limited efficacy in human antitumor clinical trials, mostly due to the profound differences in the properties and compositions of iNKT cells between the two species, including the presence of a CD8(+) subset of iNKT cells only in humans. To build reliable in vivo models for studying human iNKT cells, we recently developed the first humanized mouse model (hCD1d-KI) with human CD1d knocked in. To further humanize the mouse model, we now introduced the human invariant NKT TCRalpha-chain (Valpha24Jalpha18) into the hCD1d-knockin mice. Similar to humans, this humanized mouse model developed a subset of CD8alphabeta(+) iNKT cells among other human-like iNKT subsets. The presence of the CD8alphabeta(+) iNKT cells in the thymus suggests that these cells developed in the thymus. In the periphery, these NKT cells showed a strong Th1-biased cytokine response and potent cytotoxicity for syngeneic tumor cells upon activation, as do human CD8alphabeta(+) iNKT cells. The low binding avidity of iNKT TCRs to the human CD1d/lipid complex and high prevalence of Vbeta7 TCRbeta among the CD8(+) iNKT cells strongly point to a low avidity-based developmental program for these iNKT cells, which included the suppression of Th-POK and upregulation of eomesodermin transcriptional factors. Our establishment of this extensively humanized mouse model phenotypically and functionally reflecting the human CD1d/iNKT TCR system will greatly facilitate the future design and optimization of iNKT cell-based immunotherapies. PMID- 26157174 TI - Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1. AB - Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFNgamma and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection. PMID- 26157175 TI - Pak2 Links TCR Signaling Strength to the Development of Regulatory T Cells and Maintains Peripheral Tolerance. AB - Although significant effort has been devoted to understanding the thymic development of Foxp3(+) regulatory T cells (Tregs), the precise signaling pathways that govern their lineage commitment still remain enigmatic. Our findings show a novel role for the actin cytoskeletal remodeling protein, p21 activated kinase 2 (Pak2), in Treg development and homeostasis. The absence of Pak2 in T cells resulted in a marked reduction in both thymus- and peripherally derived Tregs, accompanied by the development of spontaneous colitis in Pak2 deficient mice. Additionally, Pak2 was required for the proper differentiation of in vitro-induced Tregs as well as maintenance of Tregs. Interestingly, Pak2 was necessary for generating the high-affinity TCR- and IL-2-mediated signals that are required by developing Tregs for their lineage commitment. These findings provide novel insight into how developing thymocytes translate lineage-specific high-affinity TCR signals to adopt the Treg fate, and they further posit Pak2 as an essential regulator for this process. PMID- 26157176 TI - Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus-Induced Immune Responses. AB - Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in children worldwide. Sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, has been associated with the induction of autophagy and the regulation of inflammatory mediators. We found that Sirt1 was upregulated in mouse lung after RSV infection. Infected animals that received EX-527, a selective SIRT1 inhibitor, displayed exacerbated lung pathology, with increased mucus production, elevated viral load, and enhanced Th2 cytokine production. Gene expression analysis of isolated cell populations revealed that Sirt1 was most highly upregulated in RSV-treated dendritic cells (DCs). Upon RSV infection, EX 527-treated DCs, Sirt1 small interfering RNA-treated DCs, or DCs from conditional knockout (Sirt1(f/f)-CD11c-Cre(+)) mice showed downregulated inflammatory cytokine gene expression and attenuated autophagy. Finally, RSV infection of Sirt1(f/f)-CD11c-Cre(+) mice resulted in altered lung and lymph node cytokine responses, leading to exacerbated pathology. These data indicate that SIRT1 promotes DC activation associated with autophagy-mediated processes during RSV infection, thereby directing efficient antiviral immune responses. PMID- 26157178 TI - Move Over, Strategic Plan: Make Way for the Culture Plan! PMID- 26157177 TI - Cutting Edge: Redox Signaling Hypersensitivity Distinguishes Human Germinal Center B Cells. AB - Differences in the quality of BCR signaling control key steps of B cell maturation and differentiation. Endogenously produced H2O2 is thought to fine tune the level of BCR signaling by reversibly inhibiting phosphatases. However, relatively little is known about how B cells at different stages sense and respond to such redox cues. In this study, we used phospho-specific flow cytometry and high-dimensional mass cytometry (CyTOF) to compare BCR signaling responses in mature human tonsillar B cells undergoing germinal center (GC) reactions. GC B cells, in contrast to mature naive B cells, memory B cells, and plasmablasts, were hypersensitive to a range of H2O2 concentrations and responded by phosphorylating SYK and other membrane-proximal BCR effectors in the absence of BCR engagement. These findings reveal that stage-specific redox responses distinguish human GC B cells. PMID- 26157179 TI - [Not Available]. PMID- 26157180 TI - Clinical Pharmacy Services in Canadian Emergency Departments: A National Survey. AB - BACKGROUND: Providing clinical pharmacy services in emergency departments (EDs) is important because adverse drug events commonly occur before, during, and after ED encounters. Survey studies in the United States have indicated a relatively low presence of clinical pharmacy services in the ED setting, but a descriptive survey specific to Canada has not yet been performed. OBJECTIVES: To describe the current status of pharmacy services in Canadian EDs and potential barriers to implementing pharmacy services in this setting. METHODS: All Canadian hospitals with an ED and at least 50 acute care beds were contacted to identify the presence of dedicated ED pharmacy services (defined as at least 0.5 full-time equivalent [FTE] position). Three different electronic surveys were then distributed by e-mail to ED pharmacy team members (if available), pharmacy managers (at hospitals without an ED pharmacy team), and ED managers (all hospitals). The surveys were completed between July and September 2013. RESULTS: Of the 243 hospitals identified, 95 (39%) had at least 0.5 FTE clinical pharmacy services in the ED (based on initial telephone screening). Of the 60 ED pharmacy teams that responded to the survey, 56 had pharmacists (27 of which also had ED pharmacy technicians) and 4 had pharmacy technicians (without pharmacists). Forty four (79%) of the 56 ED pharmacist services had been established within the preceding 10 years. Order clarification, troubleshooting, medication reconciliation, and assessment of renal dosing were the services most commonly provided. The large majority of pharmacy managers and ED managers identified the need for ED pharmacy services where such services do not yet exist. Inadequate funding, competing priorities, and lack of training were the most commonly reported barriers to providing this service. CONCLUSIONS: Although the establishment of ward-based pharmacy services in Canadian EDs has increased over the past 10 years, lack of funding and a lack of ED training for pharmacists were reported as significant barriers to the expansion of this role in most hospitals. PMID- 26157181 TI - Medication Reconciliation Practices in Canadian Emergency Departments: A National Survey. AB - BACKGROUND: As of 2015, Accreditation Canada's Qmentum program expects emergency departments (EDs) to initiate medication reconciliation for 2 groups of patients: (1) those with a decision to admit and (2) those without a decision to admit who meet the criteria of a risk-based, health care organization-defined selection process. Pharmacist-led best possible medication histories (BPMHs) obtained in the ED are considered more complete and accurate than BPMHs obtained by other ED providers, with pharmacy technicians obtaining BPMHs as effectively as do pharmacists. A current assessment of the role of pharmacy in BPMH processes in Canadian EDs is lacking. OBJECTIVES: To identify and describe BPMH and medication reconciliation practices in Canadian EDs, including those performed by members of the ED pharmacy team. METHODS: All Canadian hospitals with an ED and at least 50 acute care beds were contacted to identify the presence of dedicated ED pharmacy services (defined as at least a 0.5 full-time equivalent position). Different electronic surveys were then distributed to ED pharmacy team members (where available) and ED managers (all hospitals). RESULTS: Survey responses were obtained from 60 (63%) of 95 ED pharmacy teams and 128 (53%) of 243 ED managers. Only 38 (30%) of the 128 ED managers believed that their current BPMH processes were adequate to obtain a BPMH for all admissions. Fifty-nine (98%) of the ED pharmacy personnel reported obtaining BPMHs (most commonly 6-10 per day), with priority given to admitted patients. Only 14 (23%) of the 60 ED pharmacy teams reported that their EDs had adequate staffing to comply with Accreditation Canada's requirements for obtaining BPMHs. This result is supported by the 104 (81%) out of 128 ED managers who reported that additional ED staffing would be needed to comply with the requirements. Numerous ED managers identified the need to expand ED pharmacy services and improve information technology support. CONCLUSIONS: BPMH processes in Canadian EDs were variable and inadequately supported. Survey responses suggested that additional staff and significant improvements in structured processes would be required to meet Accreditation Canada standards. PMID- 26157182 TI - Cost-Consequence Analysis of Nitisinone for Treatment of Tyrosinemia Type I. AB - BACKGROUND: Tyrosinemia type I is a rare but severe genetic metabolic disorder. Nitisinone combined with a diet low in tyrosine and phenylalanine became first line therapy in 1994. OBJECTIVES: To estimate the direct medical costs of health care services related to the treatment of tyrosinemia type I, taking into consideration the real-life efficacy of nitisinone. METHODS: A cost-consequence analysis was performed for all children with a confirmed diagnosis of tyrosinemia type I who were treated in Quebec between January 1, 1984, and January 1, 2009. The costs of care were compared for 3 consecutive historical groups: no nitisinone (1984 to 1994), late intervention with nitisinone (first dose received between 1994 and 1997), and early intervention with nitisinone (first dose received between 1997 and 2008). Data were derived from patient charts, hospital databases, and the Regie de l'assurance maladie du Quebec and MED-ECHO administrative databases. Costs were reported in 2008 Canadian dollars. RESULTS: Nitisinone treatment was associated with significant reductions in the number and duration of hospital admissions, the number of admissions to a pediatric intensive care unit, and the number of liver transplants. The cost of hospitalization per person-year was significantly lower in the 2 groups treated with nitisinone: $673 and $5 590 for the early-intervention and late-intervention groups, respectively, as compared to $12 980 for the no-nitisinone group (p < 0.001). Hospital costs per person-year for liver transplant were $3 198 for the late-intervention group and $5 044 for the no-nitisinone group: there were no transplants in the early-intervention group. The cost of nitisinone per person year was $51 493 for the early-intervention group and $64 895 for the late intervention group. CONCLUSIONS: Nitisinone treatment significantly improved the outcomes of patients with tyrosinemia type I, while decreasing utilization of health care resources, liver transplants, and associated costs. PMID- 26157183 TI - Application of the Beers Criteria to Alternate Level of Care Patients in Hospital Inpatient Units. AB - BACKGROUND: The Beers criteria were developed to help in identifying potentially inappropriate medications (PIMs) for elderly patients. These medications are often associated with adverse events and limited effectiveness in older adults. Patients awaiting an alternate level of care (ALC patients) are those who no longer require acute care hospital services and are waiting for placement elsewhere. They are often elderly, have complex medication regimens, and are at high risk of adverse events. At the time of this study no studies had applied the Beers criteria to ALC patients in Canadian hospitals. OBJECTIVES: To determine the proportion of ALC patients receiving PIMs and the proportion experiencing selected PIM-related adverse events. METHODS: A retrospective chart review of ALC patients 65 years of age or older was performed to identify PIMs and the occurrence of selected adverse events (specifically central nervous system [CNS] events, falls, bradycardia, hypoglycemia, seizures, insomnia, gastrointestinal bleeding, and urinary tract infections). A logistic regression model with a random intercept for each patient was constructed to estimate odds ratios and probabilities of adverse events. RESULTS: Fifty-two ALC patients were included in the study. Of these, 48 (92%) were taking a PIM. Of the 922 adverse events evaluated, 407 (44.1%) were associated with a regularly scheduled PIM. Among patients who were taking regularly scheduled PIMs, there was a significantly increased probability of an adverse CNS event and of a fall (p < 0.001 for both). The most common PIM medication classes were first-generation antihistamines (24 [46%] of the 52 patients), antipsychotics (21 patients [40%]), short-acting benzodiazepines (15 patients [29%]), and nonbenzodiazepine hypnotics (14 patients [27%]). CONCLUSIONS: A high proportion of ALC patients were taking PIMs and experienced an adverse event that may have been related to these drugs. These findings suggest that the ALC population might benefit from regular medication review and monitoring to prevent or detect adverse events. PMID- 26157184 TI - Qualitative Research: Data Collection, Analysis, and Management. PMID- 26157185 TI - An Introduction to Health Care Administrative Data. PMID- 26157187 TI - Erratum: Measuring Anti-Factor Xa Activity to Monitor Low-Molecular-Weight Heparin in Obesity: A Critical Review - Correction. AB - [This corrects the article on p. 33 in vol. 68, PMID: 25762818.]. PMID- 26157186 TI - Intravenous versus Oral Acetaminophen for Pain: Systematic Review of Current Evidence to Support Clinical Decision-Making. AB - BACKGROUND: Intravenous (IV) acetaminophen is increasingly used around the world for pain control for a variety of indications. However, it is unclear whether IV administration offers advantages over oral administration. OBJECTIVE: To identify, summarize, and critically evaluate the literature comparing analgesic efficacy, safety, and pharmacokinetics for IV and oral dosage forms of acetaminophen. DATA SOURCES: A literature search of the PubMed, Embase, and International Pharmaceutical Abstracts databases was supplemented with keyword searches of Science Direct, Wiley Library Online, and Springer Link databases for the period 1948 to November 2014. The reference lists of identified studies were searched manually. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials comparing IV and oral dosage forms of acetaminophen were included if they assessed an efficacy, safety, or pharmacokinetic outcome. For each study, 2 investigators independently extracted data (study design, population, interventions, follow-up, efficacy outcomes, safety outcomes, pharmacokinetic outcomes, and any other pertinent information) and completed risk-of-bias assessments. DATA SYNTHESIS: Six randomized clinical trials were included. Three of the studies reported outcomes pertaining to efficacy, 4 to safety, and 4 to pharmacokinetics. No clinically significant differences in efficacy were found between the 2 dosage forms. Safety outcomes were not reported consistently enough to allow adequate assessment. No evidence was found to suggest that increased bioavailability of the IV formulation enhances efficacy outcomes. For studies reporting clinical outcomes, the results of risk-of-bias assessments were largely unclear. CONCLUSIONS: For patients who can take an oral dosage form, no clear indication exists for preferential prescribing of IV acetaminophen. Decision making must take into account the known adverse effects of each dosage form and other considerations such as convenience and cost. Future studies should assess multiple-dose regimens over longer periods for patients with common pain indications such as cancer, trauma, and surgery. PMID- 26157188 TI - [Not Available]. PMID- 26157189 TI - More than Just Chasing INRs: Patient-Centred Care in an Anticoagulation Clinic. PMID- 26157190 TI - Evaluation of an Educational Program for Clinical Pharmacists to Conduct Standardized Assessments for Medication-Induced Movement-Related Disorders. PMID- 26157191 TI - Should Hospital Pharmacists Provide Postdischarge Follow-Up Care to High-Risk Patients? PMID- 26157192 TI - Pharmaciens oeuvrant a la securite des patients. PMID- 26157193 TI - Pharmacists for Patient Safety. PMID- 26157196 TI - Leadership of education psychological services: fit for purpose? AB - At a time of great change for educational psychology services in England, this paper reviews current theories of leadership and proposes how an integration of key aspects of these can be applied to support a self review of leadership practice, both by individual leaders and by services. The message from current theory is that in the midst of complexity and rapid change, a primary focus on the head of service is outdated; there should instead be a focus to develop the leadership capacity of the service as a whole. Key constructs considered are systems thinking, social identity, authenticity, and leadership as social construction. PMID- 26157195 TI - Management of 3rd and 4th Degree Perineal Tears after Vaginal Birth. German Guideline of the German Society of Gynecology and Obstetrics (AWMF Registry No. 015/079, October 2014). PMID- 26157197 TI - Utility of the International Classification of Functioning, Disability and Health (ICF) for educational psychologists' work. AB - Despite embracing a bio-psycho-social perspective, the World Health Organization's International Classification of Functioning, Disability and Health (ICF) assessment framework has had limited application to date with children who have special educational needs (SEN). This study examines its utility for educational psychologists' work with children who have Autism Spectrum Disorders (ASD). Mothers of 40 children with ASD aged eight to 12 years were interviewed using a structured protocol based on the ICF framework. The Diagnostic Interview for Social and Communication Disorder (DISCO) was completed with a subset of 19 mothers. Internal consistency and inter-rater reliability of the interview assessments were found to be acceptable and there was evidence for concurrent and discriminant validity. Despite some limitations, initial support for the utility of the ICF model suggests its potential value across educational, health and care fields. Further consideration of its relevance to educational psychologists in new areas of multi-agency working is warranted. PMID- 26157194 TI - National German Guideline (S2k): Guideline for the Diagnosis and Treatment of Endometriosis: Long Version - AWMF Registry No. 015-045. AB - In this guideline, recommendations and standards for optimum diagnosis and treatment of endometriosis are presented. They are based on the analysis of the available scientific evidence as published in prospective randomized and retrospective studies as well as in systematic reviews. The guideline working group consisted of experts from Austria, Germany, Switzerland, and the Czech Republic. PMID- 26157198 TI - Mentalization-Based Treatment. AB - The concept of mentalizing has captured the interest and imagination of an astonishing range of people-from psychoanalysts to neuroscientists, from child development researchers to geneticists, from existential philosophers to phenomenologists-all of whom seem to have found it useful. According to the Thompson Reuter maintained Web of Science, the use of the term in titles and abstracts of scientific papers increased from 10 to 2,750 between 1991 and 2011. Clinicians in particular have enthusiastically embraced the idea, and have put it to innovative use in their practices. Mentalization-based treatment (MBT)-making mentalizing a core focus of therapy-was initially developed for the treatment of borderline personality disorder (BPD) in routine clinical services delivered in group and individual modalities. Therapy with mentalizing as a central component is currently being developed for treatment of numerous groups, including people with antisocial personality disorder, substance abuse, eating disorders, and at risk mothers with infants and children (A. Bateman & Fonagy, 2011). It is also being used with families and adolescents, in schools, and in managing social groups (Asen & Fonagy, 2011; Fonagy et al., 2009; Twemlow, Fonagy, & Sacco, 2005a, 2005b). In this article, we focus on MBT in the treatment of BPD. PMID- 26157199 TI - Concepts of context in music therapy. AB - In contemporary music therapy as well as in related interdisciplinary fields, the importance of context in relation to theory, research, and practice has been emphasized. However, the word context seems to be used in several different ways and conceptualizations of contextual approaches vary too. The objective of this theoretical article is to clarify traditions of language use in relation to context in music therapy. In reviewing and discussing the literature, we focus on the field of mental health care. When discussing issues related to context, this literature partly focuses on the surroundings of music therapy practice, partly on the ecology of reciprocal influences within and between situations or systems. On this basis, three types of context awareness in music therapy are identified: music therapy in context; music therapy as context; and music therapy as interacting contexts. The identified types of context awareness are exemplified through references to music therapy literature and then discussed in relation to two very different metaphors, namely context as frame and context as link. Implications for practice, research, and theory development in music therapy are suggested. PMID- 26157200 TI - "The Opposite of Treatment": A qualitative study of how patients diagnosed with psychosis experience music therapy. AB - Previous research studies regarding music therapy and severe mental illness have mainly adopted quantitative methodologies in order to study the effectiveness of music therapy interventions. Studies that have explored service users' experiences of participation in music therapy are small in number, and almost nonexistent in the field of psychosis. This study aimed to explore how mental health patients with a diagnosis of psychosis experienced participation in music therapy, in general, and more specifically how they experienced music therapy in relation to their current mental state and life situation. Nine inpatients with psychosis were interviewed using a semi-structured interview focusing on the participants' experiences of music therapy in individual sessions, groups, and performances. Through the use of interpretative phenomenological analysis, four super-ordinate themes central to the participants' experiences were found: freedom, contact, well-being, and symptom reduction. Based on the findings, mental health recovery, positive mental health, and agency are proposed as constituting a better framework for music therapy in mental healthcare than a primary focus on symptom remission and functional improvement. PMID- 26157201 TI - Plantarflexor training affects propulsive force generation during gait in children with spastic hemiplegic cerebral palsy: a pilot study. AB - [Purpose] The purpose of this preliminary study was to assess the trade-off relationship between the hip and ankle joints after plantarflexor training in children with spastic hemiplegic cerebral palsy (CP). [Subjects and Methods] Three boys aged 9, 10, and 13 years with spastic hemiplegic CP participated in the study. Gait analysis was performed using a three-dimensional motion analysis device and a floor reaction force detection device before and after plantarflexor training. Data on gait speed and stride length for both sides were collected. Peak hip and ankle powers in the sagittal plane and ankle-to-hip power ratio (A2/H3 ratio) were calculated. Plantarflexor training comprised heel raises and exercise band resistance at the participant's home (3 times/week for 12 weeks). [Results] The A2/H3 ratio increased significantly on both sides in two of three subjects after training. Peak A2 power increased significantly on both sides in subject 3 and on the affected side of subject 2. Peak H3 power decreased significantly on the non-affected side of subjects 1 and 2. [Conclusion] This study confirmed that two of three subjects demonstrated a trade-off relationship between the hip and ankle joints during gait after plantarflexor training. PMID- 26157202 TI - Tonic suppression of the soleus H-reflex during rhythmic movement of the contralateral ankle. AB - [Purpose] We investigated the effect of rhythmic ankle movement on the contralateral soleus H-reflex. The H-reflex was evoked from the right soleus muscle. [Subjects and Methods] Healthy humans rhythmically moved the left ankle (movement condition) or held the left ankle stationary (stationary condition) at one of three positions corresponding to the ankle positions at which the H-reflex was evoked in the movement condition. The background electromyographic amplitude in the right soleus muscle was maintained at 10% of the maximum voluntary contraction level, and that in the right tibialis anterior muscle was matched between the stationary and movement conditions. [Results] The soleus H-reflex was suppressed throughout all phases of contralateral rhythmic ankle movement. [Conclusion] Rhythmic movement of the contralateral joint suppresses the H-reflex in the muscle that is the prime mover of the joint homologous to the rhythmically moving joint. This inhibitory mechanism may be activated during unilateral rhythmic movement to isolate the motor control of the moving ankle from that of the contralateral stationary ankle. PMID- 26157203 TI - Test-retest reliability of the Quebec user evaluation of satisfaction with assistive technology 2.0-Korean version for individuals with spinal cord injury. AB - [Purpose] The study purpose was to investigate the test-retest reliability of the Quebec User Evaluation of Satisfaction with assistive Technology 2.0-Korean version (QUEST-K) for individuals with traumatic spinal cord injury. [Subjects and Methods] Seventy participants with spinal cord injury were enrolled in this study. The participants were assessed using the QUEST-K in two sessions conducted 3 days apart. This study also utilized the spinal cord independence measure III and modified Barthel index for determining their validity concurrently with the QUEST-K. [Results] The test-retest reliability (intraclass correlation coefficient 0.855) of the QUEST-K was high, indicating a good agreement. The results of the QUEST-K testing were not substantially positively correlated with those of the spinal cord independence measure III (r = -0.075) and Modified Barthel Index (r=-0.138). [Conclusion] The test-retest reliability of the QUEST-K was high in individuals with spinal cord injury. The QUEST-K could be a reliable measure for evaluating the satisfaction with assistive technology during functional performance in patients with spinal cord injury. The ability of the QUEST-K to detect actual changes is acceptable for research and clinical settings. PMID- 26157204 TI - The effects of combined hyperbaric oxygen therapy on patients with post-stroke depression. AB - [Purpose] To observe the effect of combined hyperbaric oxygen therapy on patients with post-stroke depression. [Subjects] Ninety patients with post-stroke depression were randomly divided into 3 groups: fluoxetine treatment group (n = 30), hyperbaric oxygen therapy group (n = 30), and hyperbaric oxygen combined treatment group (n = 30). [Methods] Fluoxetine treatment group received anti depression drugs (fluoxetine, 20 mg/day), hyperbaric oxygen therapy group received hyperbaric oxygen (once a day, 5 days/week), hyperbaric oxygen combined treatment group received fluoxetine and hyperbaric oxygen treatments as described above. All patients received routine rehabilitation therapy. Hamilton Depression Scale (HAMD), and Scandinavian Stroke Scale (SSS) scores were evaluated before and at the end of 4th week. The total effective rate of depression release between the 3 groups was also compared at the end of study. [Results] The end scores of HAMD and SSS in the 3 groups were significantly lower than those before treatment. The total effective rate of combined hyperbaric oxygen therapy group after treatment was higher than the other two groups. [Conclusions] Combined hyperbaric oxygen therapy plays an important role in the treatment of patients with post-stroke depression. The total effective rate of combined hyperbaric oxygen therapy was higher than other routine anti post-stroke depression treatments. PMID- 26157205 TI - Does restriction of glenohumeral horizontal adduction reflect posterior capsule thickening of the throwing shoulder? AB - [Purpose] Glenohumeral posterior capsule tightness possibly relates to posterior capsule thickness (PCT). The purpose of the current study was to analyze the relationships between PCT and glenohumeral range of motion (ROM) in horizontal adduction (HAdd) and internal rotation (IR). [Subjects and Methods] This study recruited 39 healthy collegiate baseball players. We measured PCT by using ultrasonography and ROM of the glenohumeral joint of the throwing shoulder by using a digital inclinometer. Pearson's correlation coefficients were calculated between PCT and HAdd or IR ROM. [Results] There was no correlation between PCT and HAdd ROM, but PCT was significantly correlated with IR ROM. [Conclusion] This result indicates that posterior shoulder capsule tightness only relates to IR ROM, and that restricted HAdd ROM might reflect tightness of other tissue, such as the posterior deltoid. PMID- 26157206 TI - The effect of neurac training in patients with chronic neck pain. AB - [Purpose] This study aimed to investigate the effects of neurac training on pain, function, balance, fatigability, and quality of life. [Subjects and Methods] Subjects with chronic neck pain who were treated in S hospital were included in this study; they were randomly allocated into two groups, i.e., the experimental group (n = 10) and the control group (n = 10). Both groups received traditional physical therapy for 3 sessions for 30 min per week for 4 weeks. The experimental group practiced additional neurac training for 30 min/day, for 3 days per week for 4 weeks. All subjects were evaluated using the visual analogue scale (VAS), the neck disability index (NDI), the biorescue (balance), the questionnaire for fatigue symptoms (fatigue), and the medical outcome 36-item short form health survey (SF-36) pre- and post-intervention. [Results] The experimental group effectively improved their pain, function, balance, fatigability, and quality of life. [Conclusion] Neurac training is thus considered an effective training program that enhances body functionality by improving pain, function, balance ability, fatigability, and quality of life in patients with chronic neck pain. PMID- 26157207 TI - Functional exercise capacity, physical activity, and respiratory and peripheral muscle strength in pulmonary hypertension according to disease severity. AB - [Purpose] This study investigated functional capacity, physical activity, and respiratory and peripheral muscle strength in different functional classes of pulmonary arterial hypertension (PAH) compared with healthy subjects. [Subjects and Methods] This study included 31 patients with class II (n = 16) or class III (n = 15) PAH, classified according to the World Health Organization. Fifteen healthy subjects served as controls. Functional capacity was assessed using the 6 minute walk test (6MWT). Physical activity was determined using the International Physical Activity Questionnaire Short Form (IPAQ-SF). Respiratory muscle strength was measured using a mouth pressure device. Peripheral muscle strength was evaluated using a dynamometer. [Results] The 3 groups had similar demographic variables (p > 0.05). There were significant differences in 6MWT distance, maximal inspiratory pressure, and IPAQ categorical classification between the 3 groups (p < 0.05). Maximal expiratory pressure; total IPAQ score; and knee extensor, shoulder abductor, and hand grip strength were significantly lower in PAH patients (classes II and III) than in healthy subjects (p < 0.05). [Conclusion] As PAH progresses, respiratory muscle strength, functional exercise capacity, and physical activity decrease. Functional class should be taken into consideration when planning rehabilitation programs for this patient group. PMID- 26157208 TI - Sensory processing dysfunction among Saudi children with and without autism. AB - [Purpose] There is a dearth of studies that have examined the occurrence of sensory processing dysfunction and its components in Saudi Arabian children with autism. Therefore, this study investigated the manifestation of sensory processing dysfunction in autism and compared the functional components of sensory processing between Saudi Arabian children with and without autism. [Subjects and Methods] A convenience sample of 46 Saudi Arabian children with autism and 30 children without autism participated in this study. The sensory processing functions of both groups were assessed with the Short Sensory Profile. [Results] The overall findings indicated that 84.8% of children with autism demonstrated definite sensory processing dysfunction. The most prevalent sensory processing dysfunctions involved the under-responsive/seeks sensation (89.13%), auditory filtering (73.90%), and tactile sensitivity (60.87%) domains. Most of the children without autism (66.66%) demonstrated typical sensory function; the most prevalent sensory processing dysfunctions involved the tactile sensitivity (33.3%), under-responsive/seeks sensation (23.33%), and movement sensitivity (20%) domains. [Conclusion] Saudi Arabian children with and without autism have clinically significant sensory dysfunctions. However, the prevalence of those sensory dysfunctions in children with autism is significantly higher than in the children without autism. PMID- 26157209 TI - The influence of gastrocnemius stretching combined with joint mobilization on weight-bearing ankle dorsiflexion passive range of motion. AB - [Purpose] The purpose of this study was to investigate the effect of gastrocnemius stretching combined with talocrural joint mobilization on weight bearing ankle dorsiflexion passive range of motion. [Subjects] Eleven male subjects with bilateral limited ankle dorsiflexion passive range of motion with knee extended participated in this study. [Methods] All subjects received talocrural joint mobilization while performing gastrocnemius stretching. Ankle dorsiflexion passive range of motion was measured using an inclinometer under weight-bearing conditions before and immediately after intervention. A paired t test was used to analyze the difference between weight-bearing ankle dorsiflexion passive range of motion pre- and post-intervention. [Results] A significant increase in weight-bearing ankle dorsiflexion passive range of motion was found post-intervention compared with pre-intervention. [Conclusion] These findings demonstrate that gastrocnemius stretching combined with joint mobilization is effective for increasing weight-bearing ankle dorsiflexion passive range of motion. PMID- 26157210 TI - Effects of controlled condylar rotation exercise on symmetrical mouth opening in patients with temporomandibular disorder. AB - [Purpose] The purpose of this study was to determine the effects of a 4-week program of active condylar rotation exercise on the extent of the lateral mandibular shift during mouth opening in patients with temporomandibular disorder. [Subjects and Methods] Patients with temporomandibular disorder (n = 12; 7 men and 5 women) were recruited. The active range of temporomandibular motion was recorded using 3-dimensional ultrasound-based motion analysis. The paired t-test was used to assess changes in lateral mandibular shift before and after active condylar rotation exercise. [Results] The degree of the lateral mandibular shift during mouth opening and the mouth opening-lateral mandibular shift ratio were significantly lower after active condylar rotation exercise than before the exercise. [Conclusion] Active condylar rotation exercise may effectively reduce the degree of the lateral mandibular shift during mouth opening to produce symmetrical mouth opening in patients with mild temporomandibular disorder. PMID- 26157211 TI - Influences of visual and supporting surface conditions on standing postural control and correlation with walking ability in patients with post-stroke hemiplegia. AB - [Purpose] To quantify the influence of visual and under-foot-surface conditions on standing balance in patients with post stroke hemiplegia and examine associations of this ordinal score with somatosensory disturbance and walking ability. [Subjects] Sixty-six patients with post-stroke hemiplegia. [Methods] Standing balance was tested in 4 conditions (firm floor or foam rubber surface with eyes open or eyes closed) for 30 s per condition and scored using a 5 category ordinal scale. The accuracy of the standing balance score to distinguish patients above/below cut-offs for the timed up-and-go test (14 s) and functional ambulation category (4) was determined. [Results] Standing balance score was correlated with sensory impairments (tactile and vibration perception) and walking ability (up-and-go and functional ambulation category). The standing balance score distinguished patients with up-and-go times <=14 and >14 s with moderate sensitivity and specificity, and distinguished patients with functional ambulation category <4 and >=4 with high sensitivity and specificity. [Conclusion] Patients with post-stroke hemiplegia may be unable to adapt to changing visual or surface conditions. Therapists should perform comprehensive balance tests. The standing balance ordinal scale score was moderately correlate with walking ability, distinguishing patients according to walking ability. This scale's validity and reliability must be assessed in clinical settings. PMID- 26157212 TI - Efficacy of pulmonary rehabilitation using cervical range of motion exercise in stroke patients with tracheostomy tubes. AB - [Purpose] In this study, stroke patients who were intubated with tracheostomy tubes performed cervical range of motion exercises, and changes in their pulmonary and coughing functions were examined. [Subjects and Methods] Twelve stroke patients who were intubated with tracheostomy tubes participated in the study. The subjects were randomly assigned to either the control group (n=6), which did not perform cervical range of motion exercises, or the experimental group (n=6), which did perform exercises. [Results] With regards to forced vital capacity, forced expiratory volume at one second, and peak cough flow rate before and after the exercises, the control group did not show any significant differences while the experimental group showed statistically significant increases in all three parameters. [Conclusion] The results indicate that cervical range of motion exercises can effectively improve the pulmonary function and coughing ability of stroke patients intubated with tracheostomy tubes, and that cervical range of motion exercises can help in the removal of tracheostomy tubes. PMID- 26157213 TI - Differences in lumbar and pelvic angles and gluteal pressure in different sitting postures. AB - [Purpose] To investigate the effects of erect sitting, slouched posture with cross-legged sitting, and erect posture with cross-legged sitting on the lumbar and pelvic angles, and gluteal pressure. [Subjects] For the experiments, 17 healthy women were recruited. [Methods] All subjects were asked to perform three sitting postures: erect sitting, slouched posture with cross-legged sitting, and erect posture with cross-legged sitting. Lumbar and pelvic angles were measured using a three-dimensional motion-capture system, and gluteal pressure was measured using a pressure mat. [Results] Compared to erector sitting, slouched posture with cross-legged sitting showed significantly greater lumbar flexion, posterior pelvic tilt, and left pelvic tilt. Compared to erect sitting, erect posture with cross-legged sitting showed significantly greater lumbar flexion and posterior pelvic tilt. Compared to erect posture with cross-legged sitting, slouched posture with cross-legged sitting showed significantly greater lumbar flexion and posterior pelvic tilt. Compared to erect sitting and erect posture with cross-legged sitting, slouched posture with cross-legged sitting showed significantly greater left gluteal pressure; there was no significant difference in right gluteal pressure. [Conclusion] An erect posture can reduce changes in lumbar and pelvic angles, and gluteal pressure compared to a slouched posture during cross-legged sitting. PMID- 26157214 TI - Effects of trunk-hip strengthening on standing in children with spastic diplegia: a comparative pilot study. AB - [Purpose] This study evaluated the effects of trunk-hip strengthening exercise on trunk-hip activation and pelvic tilt motion during standing in children with spastic diplegia and compared the improvement of pelvic tilt between the modified trunk-hip strengthening exercise and conventional exercise. [Subjects and Methods] Ten ambulant children with spastic diplegia were randomized to the modified trunk-hip strengthening exercise (n = 5) or conventional exercise (n = 5) group. The intervention consisted of a 6-week modified trunk-hip strengthening exercise 3 times per week. The children were tested for trunk-hip muscles activation and pelvic tilt motion during standing by surface electromyography and an inclinometer before and after the intervention. [Results] The anterior pelvic tilt angle and activation of the extensor spinae, rectus femoris, and semitendinosus during standing decreased significantly in the modified exercise group. The activation of extensor spinae differed significantly between groups. [Conclusion] Compared to the conventional exercise, the modified exercise was more effective for trunk-hip activation improvement and anterior pelvic tilt motion decrease during standing in children with spastic diplegia. We suggest clinicians use an individually tailored modified trunk-hip strengthening exercise for strengthening the weakest muscle groups in children with standing ability problems. PMID- 26157215 TI - Effect of heel pressure pad attached to ankle-foot orthosis on the energy conversion efficiency in post-stroke hemiplegic gait. AB - [Purpose] This study aimed to analyze the effect of heel pads in ankle-foot orthoses on dynamic motion aspects of gait in stroke patients from the viewpoint of energy conversion efficiency. [Subjects] Fourteen chronic stroke patients who were ambulatory and had lower extremity motor function categorized as Brunnstrom stage IV participated in the study. [Methods] A three-dimensional motion analysis system was used to assess the effect of heel pad intervention on dynamic motion gait parameters using a single-system A-B-A design. [Results] The results showed that a heel pad attached to the ankle-foot orthosis caused significant retention of the center-of-pressure at the heel during the heel rocker function and significant increase in the dorsiflexion moment and the height of the center of gravity. [Conclusion] The present study showed that a heel pad attached to the calcaneal region of an ankle-foot orthosis caused slight retention of the center of-pressure at the heel during the heel rocker function along with center of gravity elevation in the stance phase and improved the energy conversion efficiency, especially on the non-paretic side. PMID- 26157216 TI - The effects of changes in the sagittal plane alignment of running-specific transtibial prostheses on ground reaction forces. AB - [Purpose] To verify the effects of sagittal plane alignment changes in running specific transtibial prostheses on ground reaction forces (GRFs). [Subjects and Methods] Eight transtibial amputees who used running-specific prostheses during sprinting participated. The sprint movements were recorded using a Vicon-MX system and GRF measuring devices. The experiment levels were set as regularly recommended alignment (REG; the normal alignment for the subjects) and dorsiflexion or plantar flexion from the REG. [Results] The subjects were classified into fast (100-m personal best < 12.50 s) and slow (100-m personal best >= 12.50 s) groups. In both groups, there were no significant differences in the center of gravity speed; further, the difference in the stance time was significant in the slow group but not in the fast group. Significant differences were observed in the step length for the fast group, whereas the stance time and step rate significantly differed in the slow group. The GRF impulse showed significant differences in the vertical and braking directions in both groups. [Conclusion] The GRFs are affected by sagittal plane alignment changes in running specific prostheses. Moreover, our results suggest that the change in GRFs along with the altered sagittal plane alignment influenced the step length and step rate. PMID- 26157217 TI - The effects of task-oriented versus repetitive bilateral arm training on upper limb function and activities of daily living in stroke patients. AB - [Purpose] The purpose of this study was to investigate the effects of task oriented bilateral arm training and repetitive bilateral arm training on upper limb function and activities of daily living in stroke patients. [Subjects] Forty patients with hemiplegia resulting from stroke were divided into a task orientied bilateral arm training group (n=20) and a repetitive bilateral arm training group (n=20). [Methods] The task-oriented group underwent bilateral arm training with 5 functional tasks, and the repetitive group underwent bilateral arm training with rhythmin auditory cueing for 30 minutes/day, 5 times/week, for 12 weeks. [Results] The upper limb function and the ability to perform activities of daily living improved significantly in both groups. Although there were significant differences between the groups, the task-oriented group showed greater improvement in upper limb function and activities of daily living. [Conclusion] We recommend bilateral arm training as well as adding functional task training as a clinical intervention to improve upper limb function activities of daily living in patients with hemiplegia. PMID- 26157218 TI - Influence of transcutaneous electrical nerve stimulation on weight distribution in lower leg muscles. AB - [Purpose] The purpose of this study was to compare the effects of transcutaneous electrical nerve stimulation (TENS), with and without visual input, on weight distribution following exercise-induced fatigue in the dorsiflexor and plantar flexor muscles of the ankle. [Subjects and Methods] This study had a cross sectional design. Nineteen healthy adults (10 males, 9 females; mean age 21+/-0.8 years) were recruited to participate in a single group repeated measurements study lasting three days. On the first day, following exercise-induced fatigue, the standing position was maintained for 30 minutes, after which the postural sway was measured with eyes open (EO) and eyes closed (EC). On the second day, TENS was applied to the ankle dorsiflexors in the standing position for 30 minutes following exercise-induced fatigue. On the last day, TENS was applied to the plantar flexors, and the postural sway was measured with EO and EC following the same exercise-induced fatigue. [Results] On level terrain, with and without visual input, there was a significant difference between the baseline values and those following TENS on the tibialis anterior. On uneven terrain (simulated by a cushion), with and without visual input, there was a significant difference between the baseline values and those following TENS on the gastrocnemius. [Conclusion] Clinically, during walking on a flat surface for only a short period of time, TENS should be applied to the tibialis anterior. If walking training is performed on a variety of terrains for a longer time, TENS should be applied to the gastrocnemius. PMID- 26157219 TI - Assessing the impact of pain on the life of breast cancer survivors using the Brief Pain Inventory. AB - [Purpose] This study attempted to assess the impact of pain on the life of breast cancer survivors using the Brief Pain Inventory (BPI). [Subjects and Methods] A cross-sectional study was conducted. Participants comprised 30 women, aged 30-80 years, who had received treatment for breast cancer (surgery and complementary treatment) at least 12 months prior to the study and had reported chronic pain related to the treatment procedures. [Results] The highest scores were found for "mood" (median: 5.00 points; first quartile: 1.00 points; third quartile: 7.25 points), "normal work" (median: 5.00 points; first quartile: 0.00 points; third quartile: 8.00 points), and "sleep" (median: 4.50 points, first quartile: 0.00 points, third quartile: 8.00 points). [Conclusion] Pain exerts a negative impact primarily on mood, normal work, and sleep among breast cancer survivors. PMID- 26157220 TI - The effects of complex exercise on walking ability during direction change and falls efficacy in the elderly. AB - [Purpose] This study was to assessed the efficacy of a complex exercise program for the elderly, with respect to the effects on walking ability during direction change and on falls efficacy. [Subjects] In total, 40 subjects were selected for this study and assigned randomly to either a complex exercise (n = 20) or a general exercise (n = 20) group. [Methods] The complex exercise consisted of resistance and aerobic exercises. The exercise program was conducted three times a week for eight weeks. We assessed outcome measures of the four square step test, the figure-of-8 walk test, and the falls efficacy scale. [Results] After the intervention, the four step square test, figure-of-8 walk test, and falls efficacy scale values increased significantly in both the complex exercise program and general exercise groups. The complex exercise group showed a more significant improvement than the general exercise group in the figure-of-8 walk test step and falls efficacy scale scores. [Conclusion] Complex exercise improved walking ability during direction change and falls efficacy in elderly individuals. PMID- 26157221 TI - Clinical feasibility of cervical exercise to improve neck pain, body function, and psychosocial factors in patients with post-traumatic stress disorder: a randomized controlled trial. AB - [Purpose] To investigate the effect of cervical exercise on neck pain, disability, and psychosocial factors in patients with post-traumatic stress disorder. [Subjects] Thirty patients with post-traumatic stress disorder, who also complained of neck pain. [Methods] The cervical exercise group (n = 15) participated in cervical exercises for 30 min, 3 times/week for 6 weeks, and the control group (n = 16) underwent conventional physical therapy alone, without exercise. The exercises were performed in the following order: cervical relaxation, local muscle stabilization, and global muscle stabilization using a sling system. [Results] Compared to the control group, the cervical exercise group demonstrated significant decreases as follows: Visual analogue scale score, 4.2 vs. 1.0; Neck disability index, 3.9 vs. 1.9; and depression on the Symptom checklist-90-revised, 9.4 vs. 4.3 and on the Hopkins symptom checklist-25, 6.3 vs. 2.8. However, anxiety on the Symptom checklist-90-revised (3.1 vs. 1.3) was not significantly different. Effect sizes were as follows: Visual analogue scale score, 1.8; Neck disability index, 0.9; depression, 1.0; and anxiety on Symptom checklist-90-revised and Hopkins symptom checklist-25, 0.6 and 0.8, respectively. [Conclusion] Cervical exercise is effective in improving neck pain, disability, and efficacy of psychological treatment for depression in patients with post traumatic stress disorder. PMID- 26157222 TI - Reliability of ultrasound imaging of the transversus abdominis muscle in asymptomatic subjects. AB - [Purpose] The purpose of this study was to assess intra-rater and inter-rater procedural reliability of ultrasound imaging measurements of transversus abdominis thickness. [Subjects] Thirty therapists who attended the B Hospital in Hwaseong participated in the study. [Methods] Two examiners assessed transverse abdominis thickness at rest and during contraction. Intra-class correlation coefficient with 95% confidence interval and, standard error of measurement were calculated. [Results] The intra-rater procedural reliability of ultrasound imaging measurements of transverse abdominis thickness, assessed using the intra class correlation coefficient, was 0.65-0.86 (within-day, 0.65-0.86; between-day, 0.77-0.85). The inter-rater procedural reliability of ultrasound imaging measurements of transverse abdominis thickness, assessed using the intra-class correlation coefficient, was 0.72-0.86 (within-day, 0.72-0.86; between-day, 0.82 0.83). [Conclusion] Ultrasound imaging can be used as a reliable method for measurements of transverse abdominis thickness. PMID- 26157223 TI - Effects of robot training on bowel function in patients with spinal cord injury. AB - [Purpose] The purpose of this study was to compare the effects of body weight supported treadmill training (BWSTT) and robot-assisted rehabilitation (RAT) on bowel function in patients with spinal cord injury with respect to defecation time and defecation drug dose (enema). [Subjects] Twenty-four patients with spinal cord injury participated in the study. All subjects had an incomplete injury ranging from level T8 to L2. [Methods] The subjects were randomly divided into BWSTT and RAT groups. Walking training was provided to both groups for 20 minutes, four times a week, for one month. The defecation time and enema dose were measured before and after the experiment. [Results] The RAT group showed significant shortening of defecation time and decrease of enema dose. [Conclusion] The results demonstrated that significantly better improvement in bowel function can be achieved with RAT. PMID- 26157224 TI - Measuring cerebral hemodynamic changes during action observation with functional transcranial doppler. AB - [Purpose] The purpose of this study was to investigate the effects of action observation training (AOT) on cerebral hemodynamic changes including cerebral blood flow velocity (CBFV) and cerebral blood flow volume (CBFvol) in healthy subjects. [Subjects] Fifteen healthy subjects participated in this study. [Methods] All subjects were educated regarding AOT, and systolic peak velocity (Vs) as well as mean flow velocity (Vm) in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and posterior cerebral artery (PCA) were evaluated using functional transcranial doppler with a 2-MHz probe, before and after performing AOT. [Results] Healthy subjects showed significant differences in Vs and Vm in the MCA, ACA, and PCA after AOT compared with those before AOT. [Conclusion] Our findings indicate that AOT has a positive effect in terms of an increase in CBFV and CBFvol in healthy subjects, since the brain requires more blood to meet the metabolic demand during AOT. PMID- 26157225 TI - Prediction of motor outcomes and activities of daily living function using diffusion tensor tractography in acute hemiparetic stroke patients. AB - [Purpose] The efficacy of diffusion tensor imaging in the prediction of motor outcomes and activities of daily living function remains unclear. We evaluated the most appropriate diffusion tensor parameters and methodology to determine whether the region of interest- or tractography-based method was more useful for predicting motor outcomes and activities of daily living function in stroke patients. [Subjects and Methods] Diffusion tensor imaging data within 10 days after stroke onset were collected and analyzed for 25 patients. The corticospinal tract was analyzed. Fractional anisotropy, number of fibers, and apparent diffusion coefficient were used as diffusion tensor parameters. Motor outcomes and activities of daily living function were evaluated on the same day as diffusion tensor imaging and at 1 month post-onset. [Results] The fractional anisotropy value of the affected corticospinal tract significantly correlated with the motor outcome and activities of daily living function within 10 days post-onset and at 1 month post-onset. Tthere were no significant correlations between other diffusion tensor parameters and motor outcomes or activities of daily living function. [Conclusion] The fractional anisotropy value of the affected corticospinal tract obtained using the tractography-based method was useful for predicting motor outcomes and activities of daily living function in stroke patients. PMID- 26157226 TI - Recovery features in ulnar neuropathy at the elbow. AB - [Purpose] This study evaluated the effect of age, sex, and entrapment localization on recovery time in patients treated conservatively for ulnar neuropathy at the elbow. [Subjects] Thirty-five patients (16 women and 15 men) who were diagnosed with ulnar neuropathy at the elbow using short segment conduction studies were evaluated retrospectively. [Methods] Definition of recovey was made based on patient satisfaction. The absence of symptoms was considered as the marker of recovery. Patients who recovered within 0-4 weeks were in Group 1, and patients who recovered within 4 weeks to 6 months were in Group 2. The differences between Group 1 and Group 2 in terms of age, sex and entrapment localization were investigated. [Results] Entrapment was most frequent in the retroepicondylar groove (54.3%). No significant difference was found in terms of age and entrapment localizations between Groups 1 and 2. There was a statistically significant difference between the groups for the male sex. [Conclusion] In ulnar neuropathy at the elbow, age and entrapment localization do not affect recovery time. However, male sex appears to be associated with longer recovery time. PMID- 26157227 TI - Comparison of Maitland and Kaltenborn mobilization techniques for improving shoulder pain and range of motion in frozen shoulders. AB - [Purpose] This study compared the use of the Maitland mobilization and Kaltenborn mobilization techniques for improving pain and range of motion in patients with frozen shoulders. [Subjects and Methods] The subjects were 20 patients with frozen shoulder who visited Hospital H, Ulsan, Korea. The subjects were divided randomly into two groups to receive Maitland or Kaltenborn mobilization to the affected shoulder. Grade III anteroposterior oscillation and posterior translation were used for the Maitland and Kaltenborn mobilization groups, respectively. Pain and range of motion of external and internal rotation were evaluated pre- and post-intervention in both groups. Paired t-tests were used to compare the pre- and post-intervention results in both groups, and independent t tests were used to compare groups. [Results] Both groups exhibited significant decreases in pain post-intervention. Moreover, the range of motion of internal and external rotation increased significantly post-intervention in both groups. However, there was no significant difference between groups with respect to pain improvement or range of motion. [Conclusion] The posterior Maitland and Kaltenborn mobilization techniques are effective for improving pain and range of motion in frozen shoulder patients. Therefore, we recommend both techniques for such patients. PMID- 26157228 TI - Kinematic effect of Nintendo Wii(TM) sports program exercise on obstacle gait in elderly women with falling risk. AB - [Purpose] This study evaluated the changes in balance ability and obstacle gait after lumbar stabilization exercise and Nintendo Wii(TM) Sports in elderly at risk for falls. [Subjects and Methods] Twenty-four elderly women with at risk for falls were randomly divided into the control, lumbar stabilization exercise, and Nintendo Wii Sports groups. Static balance was measured by the Berg Balance Scale and functional reach test, dynamic balance by the timed up-and-go test, and obstacle negotiation function by crossing velocity and maximum vertical heel clearance. [Results] Both the lumbar stabilization exercise and Nintendo Wii Sports groups showed significant improvements in obstacle negotiation function after the exercise compared to the control group. Berg Balance Scale and functional reach test scores were greater in the lumbar stabilization exercise group, while the timed up-and-go test time was significantly better in the Nintendo Wii Sports groups. [Conclusion] Lumbar stabilization exercises and Nintendo Wii Sports improve falling related balance and obstacle negotiation function in elderly women at risk for falls. PMID- 26157229 TI - Risk factors for fatigue and stress among Korean police officers. AB - [Purpose] This study investigated factors that affect the health of police officers by analyzing job stress, psychosocial stress, and fatigue faced by police officers in order to provide basic data for the efficient management of police officers and future comparative research. [Subjects and Methods] Police officers admitted to the National Police Hospital from March to May 2013 were surveyed to investigate their degree of stress. The questionnaire consisted of 4 areas related to patient characteristics: general and demographic characteristics factors, job stress, psychosocial stress, and fatigue. [Results] The analysis of the relationships among job stress, psychosocial health, and fatigue showed the 0%, 44.7%, and 82% of those with healthy, potential, and high risks of stress had high job stress, respectively. Meanwhile, 40.8% and 77.9% of subjects with normal and high risks of fatigue had high job stress. [Conclusion] The studies can be used as basic and comparative data for the prevention and early control of job related diseases for police officers. PMID- 26157230 TI - Effects of the Neurac((r)) technique in patients with acute-phase subacromial impingement syndrome. AB - [Purpose] This study investigated the effects of the Neurac technique on shoulder pain, function, and range of motion in patients with acute-phase subacromial impingement syndrome. [Subjects] Thirteen patients (seven females and six males) with acute-phase subacromial impingement syndrome participated in this study. [Methods] Shoulder pain, function, and range of motion were assessed before and after the application of the Neurac technique. [Results] Pain and function scores were significantly lower after than before the Neurac intervention. Shoulder range of motion was significantly greater after Neurac intervention than before it. [Conclusion] The Neurac technique is a useful intervention for patients with acute-phase subacromial impingement syndrome. PMID- 26157231 TI - Factors associated with the annual change in forced expiratory volume in 1 second of officially acknowledged victims of pollution-related illness in improved environments: a longitudinal study. AB - [Purpose] We examined factors affecting annual change in pulmonary function in residents previously exposed to air pollution in an area where pollution has been reduced and a long time period has elapsed. [Subjects and Methods] Data of 730 officially acknowledged victims of pollution-related illness from an annual survey during 2000 to 2009 were analyzed. The primary outcome was forced expiratory volume in 1 second (FEV1), along with factors such as age, body composition, smoking habits, respiratory symptoms, and classification of medical management (an index of the need for treatment). Multiple regression analyses were used to identify factors associated with the annual change in FEV1. [Results] Three significant factors were identified: smoking habit, classification of medical management, and gender. Smoking habits and classification of medical management had stronger effects on the annual change in FEV1 than gender. [Conclusion] With an improved environment, continuation of smoking accelerates the decline in FEV1. PMID- 26157232 TI - Effects of neuromuscular joint facilitation on bridging exercises with respect to deep muscle changes. AB - [Purpose] This study examined the effects of neuromuscular joint facilitation on bridging exercises by assessing the cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis. [Subjects] Twelve healthy men. [Methods] Four exercises were evaluated: (a) supine resting, (b) bridging resistance exercise involving posterior pelvic tilting, (c) bridging resistance exercise involving anterior pelvic tilting, and (d) bridging resistance exercise involving neuromuscular joint facilitation. The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were measured during each exercise. [Results] The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were significantly greater in the neuromuscular joint facilitation group than the others. [Conclusion] Neuromuscular joint facilitation intervention improves the function of deep muscles such as the multifidus muscle and musculus transversus abdominis. Therefore, it can be recommended for application in clinical treatments such as that for back pain. PMID- 26157233 TI - Factors affecting the benefits of a six-month supervised exercise program on community-dwelling older adults: interactions among age, gender, and participation. AB - [Purpose] This study determined the effects of age, gender, and participation on the benefits of a 6-month supervised exercise program on older adults. [Subjects and Methods] Eighty-five (37 women, 48 men) community-dwelling older adults participated. The chair sit-and-reach test, the 8-foot up-and-go test, the 6 minute walk test, the Berg Balance Scale, lower-body flexibility, dynamic balance, aerobic endurance, balance, metabolic rate, muscle strength, and position sense were evaluated. Repeated-measures of analysis of variance was performed including dependent variables of age, gender, and participation in the exercise program as dependent inter-subject factors and time of assessment as an intra-subject factor. [Results] Mean exercise participation was 29.88 +/- 1.29 sessions. Flexibility, balance, position sense, and strength showed a significant main effect of time. There was a significant gender interaction for right shoulder flexion strength and knee extension strength, a significant gender participation interaction for pre-/post-intervention measures of functional mobility, and a significant age-participation interaction for flexibility. [Conclusion] Exercise training improved outcomes after 6 months of supervised exercise, but the changes were similar regardless of participation level. Changes in strength were more pronounced in men than women. PMID- 26157234 TI - Longitudinal study of bone loss in chronic spinal cord injury patients. AB - [Purpose] This prospective longitudinal study evaluated the changes in bone metabolism markers and bone mineral density of spinal cord injury patients over 3 years. We also assessed the relationships among the bone mineral density, bone metabolism, and clinical data of spinal cord injury patients. [Subjects and Methods] We assessed the clinical data (i.e., immobilization due to surgery, neurological status, neurological level, and extent of lesion) in 20 spinal cord injury patients. Bone mineral density, and hormonal and biochemical markers of the patients were measured at 0, 6, 12, and 36 months. [Results] Femoral neck T score decreased significantly at 36 months (p < 0.05). Among the hormonal markers, parathyroid hormone and vitamin D were significantly elevated, while bone turnover markers (i.e., deoxypyridinoline and osteocalcin) were significantly decreased at 12 and 36 months (p < 0.05). [Conclusion] Bone mineral density of the femoral neck decreases significantly during the long-term follow up of patients with spinal cord injury due to osteoporosis. This could be due to changes in hormonal and bone turnover markers. PMID- 26157235 TI - Effects of a 12-week healthy-life exercise program on oxidized low-density lipoprotein cholesterol and carotid intima-media thickness in obese elderly women. AB - [Purpose] This study examined the effects of a 12-week exercise program on plasma level of oxidized low-density lipoprotein cholesterol in obese elderly women, who are at increased risk of heart disease morbidity. [Subjects and Methods] Twenty participants were assigned into either a control (n = 10) or a supervised exercise program (n = 10) group. The 12-week exercise intervention was performed 3 days per week and involved combined aerobic exercise, resistance exercise, and traditional Korean dance. [Results] Two-factor analysis of variance revealed significant group * time interactions for body mass, diastolic blood pressure, appendicular muscle mass. For high-density lipoprotein cholesterol, oxidized low density lipoprotein cholesterol, and the ratio of oxidized low-/high-density lipoprotein cholesterol, two-factor analysis of variance revealed significant interactions (group * time), indicating responses differed significantly between the control and exercise groups after 12 weeks. [Conclusion] A 12-week low- to moderate-intensity exercise program appears to be beneficial for obese elderly women by improving risk factors for cardiovascular disease. PMID- 26157236 TI - Effects of self-selected dehydration and meaningful rehydration on anaerobic power and heart rate recovery of elite wrestlers. AB - [Purpose] This study aimed to verify the effects of self-directed weight loss on lower- and upper-body power, fatigue index, and heart rate recovery immediately before a meaningful competition (12 hours of recovery). In addition, this study tested the hypothesis that weight loss provides advantages in strength and power, as the relative power of the wrestlers is higher than that of opponents in the same weight class who do not reduce weight. [Subjects and Methods] Eleven well trained wrestlers volunteered for the study. At baseline, their mean +/- SD age, body mass, and height were 20.45 +/- 2.69 years, 74.36 +/- 9.22 kg, and 177 +/- 5.71 cm, respectively. Repeated-measures one-way analysis of variance was performed to analyze differences. [Results] Rapid weight loss achieved by restriction of energy and fluid intake resulted in exercise-impaired decreases in peak power and increased fatigue index. Moreover, weight loss by dehydration negatively affected cardiovascular stability. [Conclusion] Most of the negative effects of rapid weight loss disappear after a 12-hour recovery period, and relative peak power increases after weight loss. PMID- 26157237 TI - Aerobic training during hemodialysis improves body composition, muscle function, physical performance, and quality of life in chronic kidney disease patients. AB - [Purpose] We assessed the influences of individualized aerobic training on body composition, knee joint muscle function, physical performance, and quality of life in chronic kidney disease patients. [Subjects] Ten chronic kidney disease patients undergoing dialysis. [Methods] Overall physical function and quality of life before and after 12 weeks of aerobic training were evaluated by body composition, the six-minute walk test, cardiopulmonary exercise tests, and Short Form 36-item questionnaire. [Results] The six-minute walk test distance increased significantly after 12 weeks aerobic training. Resting metabolic rate, lactate threshold, maximum oxygen uptake, and quality of life tended to increase after training. Post-training weight, muscle mass, body fat mass, fat percentage, body mass index, and peak torque of right and left knee extension and flexion did not change significantly. [Conclusion] Intra-dialytic training can a safe approach to maintain or improve physical performance and quality of life of chronic kidney disease patients undergoing hemodialysis without adverse events or negative cardiovascular responses. Aerobic training may prevent a decline in body composition and knee joint muscle function due to inactivity in chronic kidney disease patients. Clinically, aerobic training may initially be adapted to maintain overall physical function or improve quality of life in chronic kidney disease patients undergoing hemodialysis. PMID- 26157238 TI - Effects of yoga exercise on maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity in female patients with skeletal muscle pain syndrome. AB - [Purpose] This study analyzed the effects of yoga exercise on maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity in female patients with skeletal muscle pain syndrome. [Subjects] The subjects were 24 female patients with skeletal muscle pain syndrome. [Methods] The subjects were divided into 2 groups: a yoga exercise group (n = 12) and a non-exercise control group (n = 12). Body composition, maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity were measured before and after a 12-week yoga exercise program. [Results] After the 12-week yoga exercise program, the exercise group exhibited slightly higher maximum oxygen uptake and creatine kinase myocardial bond activity than the control group, but the differences were not statistically significant. In addition, the exercise group exhibited a significant decrease in cortisol level. [Conclusion] Regular and continuous aerobic exercise such as yoga improves body composition, maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity in female patients with skeletal muscle pain syndrome. PMID- 26157239 TI - Effects of kinesiology taping on the upper-extremity function and activities of daily living in patients with hemiplegia. AB - [Purpose] This study determined the effects of kinesiology taping on the upper extremity function and activities of daily living of patients with hemiplegia. [Subjects] The experimental group and control group comprised 15 hemiplegia patients each. [Methods] This study was performed from June 4 to December 22, 2012, involving 30 hemiplegia patients. The experimental and controls groups performed task practices for 30 minutes, 3 times per week for 28 weeks with and without taping, respectively. [Results] After treatment, there were significant differences in every outcome measures within each group except for the Brunnstrom recovery stage of the hand. However, there was a significant difference in functional independence movements between the groups. [Conclusion] Task practice has the same effectiveness regardless of the taping of the upper extremities. Nevertheless, taping is helpful for improving both the functions and activities of daily living in patients with hemiplegia. PMID- 26157240 TI - The effects of stair gait training using proprioceptive neuromuscular facilitation on stroke patients' dynamic balance ability. AB - [Purpose] This study aims to examine stroke patients' changes in dynamic balance ability through stair gait training where in proprioceptive neuromuscular facilitation (PNF) was applied. [Subjects and Methods] In total 30 stroke patients participated in this experiment and were randomly and equally allocated to an experimental group and a control group. The experimental group received exercise treatment for 30 min and stair gait training where in PNF was applied for 30 min and the control group received exercise treatment for 30 min and ground gait training where in PNF was applied for 30 min. For the four weeks of the experiment, each group received training three times per week, for 30 min each time. Berg Balance Scale (BBS) values were measured and a time up and go (TUG) test and a functional reach test (FRT) were performed for a comparison before and after the experiment. [Results] According to the result of the stroke patients' balance performance through stair gait training, the BBS and FRT results significantly increased and the TUG test result significantly decreased in the experimental group. On the contrary, BBS and FRT results did not significantly increase and the TUG test result did not significantly decrease in the control group. According to the result of comparing differences between before and after training in each group, there was a significant change in the BBS result of the experimental group only. [Conclusions] In conclusion, the gait training group to which PNF was applied saw improvements in their balance ability, and a good result is expected when neurological disease patients receive stair gait training applying PNF. PMID- 26157241 TI - Effects of passive static stretching on blood glucose levels in patients with type 2 diabetes mellitus. AB - [Purpose] This study determined the effects of passive static stretching on blood glucose levels in patients with type 2 diabetes. [Subjects] Fifteen patients (8 males and 7 females) with type 2 diabetes were recruited and randomly assigned to the control group or passive static stretching group. [Methods] Glycated hemoglobin was measured before and after the 8-week training period. [Results] Glycated hemoglobin levels decreased significantly in the passive static stretching group, and there were significant differences in blood glucose levels between the 2 groups. [Conclusion] Passive static stretching of the skeletal muscles may be an alternative to exercise to help regulate blood glucose levels in diabetes patients. PMID- 26157242 TI - Tai chi improves cognitive and physical function in the elderly: a randomized controlled trial. AB - [Purpose] To investigate the effect of Tai Chi on cognitive and physical function in the elderly. [Subjects and Methods] A randomized trial design was used. A total 150 subjects were enrolled and were divided into Tai Chi and control groups. Subjects in the Tai Chi group participated Tai Chi for 6 months, and subjects in the control group participated in other non-athletic activities. [Results] There were no differences between the groups in the one leg standing time with eyes open, left grip strength, or the Frontal Assessment Battery at bedside after 3 and 6 months of intervention. The Mini-Mental State Examination scores after 3 and 6 months were higher in the Tai Chi group than in the control group. The right grip strength after 3 months increased more in the Tai Chi group than in the control group. Both the 5-m high walking speed and 10-m normal walking speed were significantly lower after 3 and 6 months of Tai Chi practice. [Conclusion] These results suggest that regular Tai Chi practice may improve cognitive and physical function in the elderly. PMID- 26157243 TI - Comparison of neck and upper-limb muscle activities between able-bodied and paraplegic individuals during wheelchair propulsion on the ground. AB - [Purpose] This study compared the muscle activities of the neck and upper-limb muscles between able-bodied individuals and persons with paraplegia during wheelchair propulsion on the ground. [Subjects and Methods] The muscle activities of the neck and upper-limb muscles of 8 normal individuals and 8 individuals with paraplegia were analyzed during wheelchair propulsion. The activities of the latissimus dorsi, pectoralis major, anterior/posterior deltoids, triceps brachii, extensor carpi radialis, and sternocleidomastoid muscles were assessed. [Results] The paraplegic group showed significantly higher sternocleidomastoid activity than the normal group. Latissimus dorsi activity was also higher in the paraplegia group than in the normal group, but the difference was not significant. There were no significant differences in the other muscle activities between groups. [Conclusion] Paraplegic patients tend to use the sternocleidomastoid and latissimus dorsi muscles with greater degrees of activity. Therefore, physiotherapists should not overlook the treatment of these muscles for paraplegic patients who are long-term wheelchair users. PMID- 26157244 TI - Development of an ankle torque measurement device for measuring ankle torque during walking. AB - [Purpose] To develop a device for measuring the torque of an ankle joint during walking in order to quantify the characteristics of spasticity of the ankle and to verify the functionality of the device by testing it on the gait of an able bodied individual and an equinovarus patient. [Subjects and Methods] An adjustable posterior strut (APS) ankle-foot orthosis (AFO) was used in which two torque sensors were mounted on the aluminum strut for measuring the anterior posterior (AP) and medial-lateral (ML) directions. Two switches were also mounted at the heel and toe in order to detect the gait phase. An able-bodied individual and a left hemiplegic patient with equinovarus participated. They wore the device and walked on a treadmill to investigate the device's functionality. [Results] Linear relationships between the torques and the corresponding output of the torque sensors were observed. Upon the analyses of gait of an able-body subject and a hemiplegic patient, we observed toque matrices in both AP and ML directions during the gait of the both subjects. [Conclusion] We developed a device capable of measuring the torque in the AP and ML directions of ankle joints during gait. PMID- 26157245 TI - The immediate effect of neuromuscular joint facilitation (NJF) treatment on the standing balance in younger persons. AB - [Purpose] The aim of this study was to investigate the change in standing balance of younger persons after neuromuscular joint facilitation (NJF) treatment. [Subjects] The subjects were 57 healthy young people, who were divided into three groups: The NJF group, and the Proprioceptive Neuromuscular Facilitation (PNF) group and the control group. [Methods] Functional reach test and body sway were measured before and after intervention in three groups. Four hip patterns of NJF or PNF were used. Two-way ANOVA and multiple comparisons were performed. [Results] The rate of change of FRT in the NJF group increased than the PNF group. The root mean square area at NJF and PNF group increased than control group. [Conclusion] The results suggest that caput femoris rotation function can be improved by NJF treatment, and that improvement of caput femoris rotation contributes to improve dynamic balance. PMID- 26157246 TI - Effects of high voltage pulsed current stimulation with a visible contraction intensity on expression of TGF-beta1 and synthesis of type I collagen in wound induced white rats. AB - [Purpose] This study aimed to examine the expression of transforming growth factor beta1 (TGF-beta1) and type I collagen by applying high voltage pulsed current stimulation (HVPCS) with a visible contraction intensity to white rats with induced wounds. [Subjects] Thirty-six white rats were used for this study. HVPCS with a non-visible contraction intensity was applied to experimental group I, and HVPCS with a visible contraction intensity was applied to experimental group II. Placebo stimulation was applied to the control group. [Methods] After wounds were triggered, the intervention appropriate for each group was applied. Changes in the size of their wounds and expression of TGF- beta1 and type I collagen were measured on the third, fifth, and seventh days. [Results] Comparison of the sizes of the wounds among the groups showed that the most significant decreases were found in experimental group II on the fifth and seventh days. TGF-beta1 expression comparison revealed that experimental group II had the most expression on the fifth day. [Conclusion] HVPCS with a visible contraction intensity was effective in promoting wound healing by increasing expression of TGF-beta1 and synthesis of type I collagen. PMID- 26157247 TI - Comparison of isokinetic muscle strength and muscle power by types of warm-up. AB - [Purpose] The purpose of this study was to clarify the influence of static stretching at warm-up on the isokinetic muscle torque (at 60 degrees /sec) and muscle power (at 180 degrees /sec) of the flexor muscle and extensor muscle of the knee joint. [Subjects and Methods] The subjects of this study were 10 healthy students with no medically specific findings. The warm-up group and warm-up with stretching group performed their respective warm-up prior to the isokinetic muscle torque evaluation of the knee joint. One-way ANOVA was performed by randomized block design for each variable. [Results] The results were as follows: First, the flexor peak torque and extensor peak torque of the knee joint tended to decrease at 60 degrees /sec in the warm-up with stretching group compared with the control group and warm-up group, but without statistical significance. Second, extensor power at 180 degrees /sec was also not statistically significant. However, it was found that flexor power increased significantly in the warm-up with stretching group at 180 degrees /sec compared with the control group and warm-up group in which stretching was not performed. [Conclusion] Therefore, it is considered that in healthy adults, warm-up including two sets of stretching for 20 seconds per muscle group does not decrease muscle strength and muscle power. PMID- 26157248 TI - Comparing trapezius muscle activity in the different planes of shoulder elevation. AB - [Purpose] The purpose of this study was to compare the upper, middle, and lower trapezius muscles' activity in the different planes of shoulder elevation. [Subjects] Twenty male subjects volunteered for this study. [Methods] Surface electromyographic (EMG) activity for each of the three regions of the trapezius muscles in the three different planes of elevation were collected while the participants maintained 30, 60, and 90 degrees of elevation in each plane. The EMG data were normalized with maximum voluntary isometric contraction (%MVIC), and compared among the planes at each angle of elevation. [Results] There were significantly different muscle activities among the elevation planes at each angle. [Conclusion] This study found that the three regions of the trapezius muscles changed their activity depending on the planes of shoulder elevation. These changes in the trapezius muscles could induce appropriate scapular motion to face the glenoid cavity in the correct directions in different planes of shoulder elevation. PMID- 26157249 TI - The effects of mirror therapy with tasks on upper extremity function and self care in stroke patients. AB - [Purpose] The purpose of this study was to determine the effects of mirror therapy with tasks on upper extremity unction and self-care in stroke patients. [Subjects] Thirty participants were randomly assigned to either an experimental group (n=15) or a control group (n=15). [Methods] Subjects in the experimental group received mirror therapy with tasks, and those in the control group received a sham therapy; both therapies were administered, five times per week for six weeks. The main outcome measures were the Manual Function Test for the paralyzed upper limb and the Functional Independence Measure for self-care performance. [Results] The experimental group had more significant gains in change scores compared with the control group after the intervention. [Conclusion] We consider mirror therapy with tasks to be an effective form of intervention for upper extremity function and self-care in stroke patients. PMID- 26157250 TI - Different cutoff values for 10-m walking speed simply classification of walking independence in stroke patients with or without cognitive impairment. AB - [Purpose] The aim of this study was to determine the threshold for classifying walking independence in stroke patients with and without cognitive disorders. [Subjects] The subjects were 130 patients with initial stroke hemiplegia. [Methods] The following factors were analyzed for associations with walking independence: Brunnstrom stage, one-leg standing time on the paralytic side, one leg standing time on the non-paralytic side, and 10-m walking speed. We classified the patients with Mini-Mental State Examination (MMSE) scores >=24 points into the high-score group and those with MMSE scores of <=23 points into the low-score group and examined the main factors and cutoff values associated with walking independence in each group. [Results] The high-score group included 69 subjects (53.1%), and the low-score group included 61 subjects (46.9%). The primary factor associated with high MMSE scores among the stroke patients was the 10-m walking time. Using a cutoff level for the 10-m walking speed of 41.4 m/min resulted in a positive likelihood ratio of 6.3. The primary factor associated with low MMSE scores among the stroke patients was the 10-m walking time. Using a cutoff level for the 10-m walking speed of 48.0 m/min resulted in a positive likelihood ratio of 7.6. [Conclusion] The cutoff value for the 10-m walking speed can be used to evaluate walking independence in patients with stroke among patients with high or low MMSE scores. PMID- 26157251 TI - The effects of squatting with visual feedback on the muscle activation of the vastus medialis oblique and the vastus lateralis in young adults with an increased quadriceps angle. AB - [Purpose] The purpose of this study was to identify the effects of performing squat exercises with visual feedback on the activation of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles in young adults with an increased quadriceps angle (Q-angle). [Subjects] This study used a motion analysis program (Dartfish, Switzerland) to select 20 young adults with an increased Q-angle, who were then divided into a squat group that received visual feedback (VSG, n=10) and a squat group that received no visual feedback (SG, n=10). [Methods] The intensity of exercises was increased every two weeks over a six-week exercise period in both groups. A visual marker was attached to the patella of the subjects in the VSG, and they then performed squat exercises with a maximum of 90 degrees of knee flexion within a route marked on a mirror. The SG performed squat exercises with a maximum 90 degrees of knee flexion without attaching a visual feedback device. [Results] Analysis of the muscle activation due to 90 degrees squat exercises indicated that both groups had statistically significant increases in activation of the VL. The VSG exhibited statistically significant increases in activation of the VMO. [Conclusion] This study confirmed that squat exercises with visual feedback are effective in activation of the VMO and VL muscles. The findings are meaningful in terms of preventing the occurrence of patellofemoral pain. PMID- 26157252 TI - Reproducibility and validity of the 50-meter walking test in community-dwelling elderly. AB - [Purpose] This study aimed to investigate the reproducibility and validity of the 50-m walking test. [Subjects] Reproducibility was investigated in 19 community dwelling elderly women (mean age, 76.3 years), and validity was investigated in 31 community-dwelling elderly individuals (12 men and 19 women; mean age, 75.7 years). [Methods] The time taken to walk 50 m, the time taken to walk each 10-m section (laps 1-5), the time taken to walk 10 m, and grip strength were measured. In addition, the functional reach test (FRT), one-leg standing test, and timed up and go (TUG) test were performed. [Results] In a reproducibility analysis, the interclass correlation coefficient (1,1) was 0.97. In a Bland-Altman analysis, no systematic error was found. The measured values from the 50-m walking test included a measurement error of 1.5 s, and the acceptable margin of error was confirmed to be 3.1 s. In a validity analysis, the 50-m walking test score was significantly correlated with the 10-m walking and TUG test scores. [Conclusion] Our results suggest that the 50-m walking test score may be a useful index of the walking ability of community-dwelling elderly. PMID- 26157253 TI - Effects of combined exercise on changes of lower extremity muscle activation during walking in older women. AB - [Purpose] The purpose of this study was to demonstrate the effects of combined exercise for a period of 12 weeks on the changes in lower extremity muscle activation during walking in older women. [Subjects] The subjects of this study were 22 elderly women who were 65 years of age or older and living in B-City. The subjects had no nervous system or muscular system diseases that might affect walking in the previous two years. [Methods] Muscle activation was measured by using surface EMG (QEMG-8, Laxtha, Daejeon, Republic of Korea). The subjects were asked to walk on an 8 m of footpath at a natural speed. In order to minimize the noise from the cable connecting the EMG measuring instrument to the electrodes, tape was used to affix the electrodes so that they would not fall off the subjects. The EMG data were analyzed by using the RMS. [Results] Muscle activation of the rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius was increased significantly after combined exercise for 12 weeks. However, no increase was observed in the left biceps femoris. [Conclusion] It was demonstrated that our exercise program, which includes aerobic walking exercises, senior-robics, and muscle strengthening exercises using elastic bands, is very effective for reorganizing the normal gait pattern in the cerebral cortex and improving muscle strength. PMID- 26157254 TI - The effects of core muscle release technique on lumbar spine deformation and low back pain. AB - [Purpose] The purpose of this study was to examine the effects of the core muscle release technique on correction of lumbar deformation and alleviation of low back pain. [Subjects] Ninety patients diagnosed with lumbar deformation and low back pain participated in this study. [Methods] The participants were divided into three groups according to method of treatment. The first group was treated with the core muscle release technique (CRT), the second group was treated with general exercise, and the third group was treated with electrotherapy. The core muscle release technique group received 50-minute of the core muscle release technique 5 times a week for 2 weeks, and the participants in this group were instructed not to receive any other treatments. After the 2 weeks of treatment, the patients were reexamined. The general exercise group performed Williams flexion exercises and McKenzie extension exercises 5 times a week for 2 weeks. The electrotherapy group was treated by application of electrotherapy with an interferential current therapy machine (TM-301. TOPMED. Seongnam, Republic of Korea) to the abdominal muscles and back muscles of the lumbar region. [Results] The data suggest that the core muscle release technique, general exercise, and electrotherapy all helped to decrease the alignment angle and VAS score. Of these treatment methods, however, the core muscle release technique was the most effective for treatment of lumbar spine deformation and low back pain. [Conclusion] The core muscle release technique was most effective for correction of lumbar spine deformation and pain alleviation. PMID- 26157255 TI - Comparison of ankle plantar flexor activity between double-leg heel raise and walking. AB - [Purpose] We aimed to evaluate the difference in the muscle activity between the double-leg heel raise (DHR) and treadmill walking. [Subjects] Thirty healthy males aged 21.5 +/- 1.6 years (body mass 63.6 +/- 9.3 kg, height 171.0 +/- 4.5 cm) participated in the study. [Methods] Electromyograms were simultaneously recorded from both heads of the gastrocnemius and the soleus of the right side during the DHR and treadmill walking. The DHR conditions were maximum plantar flexion (MPF), 3/4 MPF, 2/4 MPF, and 1/4 MPF, and the walking speeds were 20, 40, 60, 80, and 100 m/min. [Results] The muscle activity during the DHR and walking significantly increased with increments in the height of the heel raise and walking speed, respectively. Comparison of the muscle activity at MPF with that at each walking speed revealed that the muscle activity in the soleus and gastrocnemius medial head during walking exceeded that during the DHR in less than 3.3% of cases. [Conclusion] The DHR test is useful for evaluating the ankle plantar flexor activity necessary for walking. PMID- 26157256 TI - The effects of ankle loads on balance ability during one-leg stance. AB - [Purpose] The purpose of this study was to evaluate the effects of ankle loads on balance ability and to suggest an appropriate load amount. [Subjects and Methods] The 31 healthy subjects randomly put 0%, 1%, and 2% body weight loads on their ankles using a strap, and limit of stability was measured using a Biorescue system. Limits of stability were measured for 10 seconds using their dominant leg in the left, right, forward, and backward directions. [Results] All values for limit of stability increased significantly with the 1% load compared with the 0% load during a one-leg stance. However, all values except for the backward limit of stability showed a significant decrease with the 2% load compared with the 1% load. There was a significant difference between the 0% and 2% loads. [Conclusion] Application of loads on the ankles can be used as a training method for improving balance ability, and to increase efficiency, it is appropriate to apply 1% of the subject's body weight. PMID- 26157257 TI - Effects of a healthy life exercise program on arteriosclerosis adhesion molecules in elderly obese women. AB - [Purpose] The aim of this study was to investigate the change in the arteriosclerosis adhesion molecules after a healthy life exercise program that included aerobic training, anaerobic training, and traditional Korean dance. [Subjects] The subjects were 20 elderly women who were over 65 years of age and had 30% body fat. [Methods] The experimental group underwent a 12-week healthy life exercise program. To evaluate the effects of the healthy life exercise program, measurements were performed before and after the healthy life exercise program in all the subjects. [Results] After the healthy life exercise program, MCP-1 and the arteriosclerosis adhesion molecules sE-selectin and sVCAM-1 were statistically significantly decreased. [Conclusion] The 12-week healthy life exercise program reduced the levels of arteriosclerosis adhesion molecules. Therefore, the results of our study suggest that a healthy life exercise program may be useful in preventing arteriosclerosis and improving quality of life in elderly obese women. PMID- 26157258 TI - Effects of clinical practice focusing on level-3 OSCE items. AB - [Purpose] This study examined the effects of clinical training focusing on level 3 OSCE (analytical and therapeutic skills) items, and compared the achievement levels of physical (PT) and occupational (OT) therapist students. [Subjects] A total of 282 (165 PT and 117 OT) students enrolled at our university between 2008 and 2010 were studied. [Methods] OSCE scores were compared between before and after clinical training focusing on level-3 OSCE items, and between PT and OT students. [Results] Scores for 5 out of the 6 level-3a items were significantly higher after than before clinical training. Increases in scores of 2 or 3 level 3b and -3c items were also observed after clinical training. There were no marked differences between PT and OT students in scores for level-3a, -3b, and -3c items before clinical training. In contrast, after clinical training, OT students' scores for 3a and 3c items related to dressing were higher than those of PT students, and the latter's scores for 3b items related to transfer were higher than those of the former. [Conclusion] The results suggest level-3 OSCE items are effectively taught during clinical training. PMID- 26157259 TI - Relationships among hearing loss, cognition and balance ability in community dwelling older adults. AB - [Purpose] The purpose of this study was to determine the relationships among hearing loss, cognition, and balance ability in elderly individuals. [Subjects and Methods] In total, 46 elderly individuals over 65 years of age who were attending senior welfare centers participated in this study. Through a hearing test, the speech frequency pure tone average in the better ear was checked. We set a criterion of hearing loss if the better ear hearing level (BEHL) value was 25 dB or more. Cognition ability was evaluated using the Korean mini-mental state examination (K-MMSE). Dynamic balance ability was evaluated by the timed up and go (TUG) test, and static balance ability was tested using a one-leg stance test (OLST). [Results] The ages of the subjects were all related to BEHL, TUG, K-MMSE, and OLST. BEHL had a negative correlation with OLST, whereas it had no correlation with K-MMSE or TUG. The hearing loss group had a significantly shorter OLST time than the normal hearing group. [Conclusion] As elderly individuals get older, their hearing and cognition, as well as their balance abilities deteriorate. The results of this study indicate there is a significant correlation between hearing loss and static balance. PMID- 26157260 TI - The mediating effect of caregiver burden on the caregivers' quality of life. AB - [Purpose] Quality of life (QoL) can be closely related to caregiver burden, which may be a potential mediating effect on the relationships among stroke patient caregivers. This study investigated the predictors of caregiver's QoL based on patient and caregiver characteristics, with caregiver burden as a mediator. [Methods] This study was conducted using surveys, a literature review, and interviews. Survey data were collected from 238 subjects, who were diagnosed with stroke, and their family caregivers from October 2013 to April 2014. [Results] Caregiver health status, income, spouses caring for patients, and duration of hospitalization were identified as significant predictors of caregivers' QoL with a mediating effect of caregiver burden. The time spent on caregiving per day and patient education level were the only direct predictors of caregivers' QoL. [Conclusion] The responsibility of caring for patients with stroke, in particular for a spouse, must be administered by means of a holistic family-centered rehabilitation program. In addition, financial support and availability of various health and social service programs must be comprehensively provided in order to maintain caregivers' well-being. PMID- 26157261 TI - Comparison of the effects of hamstring stretching using proprioceptive neuromuscular facilitation with prior application of cryotherapy or ultrasound therapy. AB - [Purpose] Stretching using proprioceptive neuromuscular facilitation involve physiological reflex mechanisms through submaximal contraction of agonists which activate Golgi organ, promoting the relaxation reflex. The aim of this study was to evaluate the effects of proprioceptive neuromuscular facilitation alone and with prior application of cryotherapy and thermotherapy on hamstring stretching. [Subjects and Methods] The sample comprised of 32 young subjects with hamstring retraction of the right limb. The subjects were randomly allocated to four groups: the control, flexibility PNF, flexibility PNF associated with cryotherapy, flexibility PNF in association with ultrasound therapy. [Results] After 12 stretching sessions, experimental groups showed significant improvements compared to the control group. Moreover, we did not find any significant differences among the experimental groups indicating PNF stretching alone elicits similar results to PNF stretching with prior administration of cryotherapy or thermotherapy. [Conclusion] PNF without other therapy may be a more practical and less expensive choice for clinical care. PMID- 26157262 TI - Immediate effects of the activation of the affected lower limb on the balance and trunk mobility of hemiplegic stroke patients. AB - [Purpose] The purpose of this study was to determine the effects of the activation of the affected lower limb on balance and the trunk hemiplegic mobility of stroke patients. [Subjects] The gait group (GG) consisted of 6 subjects with hemiplegia and the non-gait group (NGG) consisted of 6 hemiplegic subjects. [Methods] The subjects in both groups were given foot facilitation training once for 30 min. The Spinal Mouse was used to measure the spinal alignment and the Berg balance scale (BBS) and sensory tests were also performed. [Results] In the GG, the sacral hip in upright to flexion, the lumbar spine in upright to extension, and the sacral hip and lumbar spine in flexion to extension showed significant increases in their angles after the intervention. In addition, there was a significant increase in the angle of the lumbar spine during extension from an upright position in the NGG. The BBS scores of both groups also increased significantly. [Conclusion] The intervention resulted in improvements in the angle of anterior pelvic tilt in the GG, and subjects in the NGG showed more extension of the thorax, which was regarded as compensation to avoid falling forward when flexing from an upright position. However, when extending backward from an upright position, both groups tended to control balance by using more lumbar flexion to keep the center of mass (COM) within the base of support (BOS). Both groups had better BBS scores. PMID- 26157263 TI - The changes in shoulder rotation strength ratio for various shoulder positions and speeds in the scapular plane between baseball players and non-players. AB - [Purpose] This study aimed to investigate the effect of shoulder positions and speeds on internal and external rotation torque of college baseball players and age-matched non-players. [Subjects] Twenty first-level collegiate baseball players and 19 college students were recruited. [Methods] A dynamometer system was used to evaluate the shoulder rotation strength in sitting postures. Three testing positions, namely shoulder abduction of 45 degrees , 70 degrees , and 90 degrees in the scapular plane, were combined with three testing speeds at 60 degrees /s, 120 degrees /s, and 210 degrees /s. [Results] The maximum external and internal rotation torques both occurred at shoulder abduction of 70 degrees . However, only external rotation torque was affected by the speed, with the peak value observed at 60 degrees /s. The internal rotation torque of baseball players was larger than that of the control group under all testing conditions, but the external rotation did not show any difference. The ratio of external to internal rotation torque changed with the testing positions and speeds in both groups. The ratio in the control group was greater than that in the player group. [Conclusion] The shoulder position could affect the rotational strength, and the baseball players could strengthen their external rotators for better performance and injury prevention. PMID- 26157264 TI - Factors influencing BMI classifications of Korean adults. AB - [Purpose] This study aimed to identify factors influencing the BMI classifications of 3,583 Korean adults using data from the fifth Korean National Health and Nutrition Examination Survey. [Subjects and Methods] Measures included lifestyle factors, physiologic factors, perceived health state, stress, subjective body recognition, health-related quality of life, and weight control behavior. [Results] Body perception scores were lower with underweight and higher with overweight and obesity than with a healthy weight. There was a lower proportion of underweight men and a higher proportion of overweight or obese men than women. Instances of Alcohol Use Identification Scores (AUDIT) >= 9 were proportionately lower with underweight and more with overweight or obesity relative to an AUDIT score < 9 with healthy weight. Hemoglobin A1c and systolic blood pressure were higher with obesity than with healthy weight. The total cholesterol level was greater with overweight and obesity than with healthy weight. [Conclusion] These results suggest that obesity intervention for adults should be based on age and sex and should include drinking habits and physical activity. PMID- 26157265 TI - Cardiorespiratory endurance in children with and without cerebral palsy as measured by an ergometer: a case series study. AB - [Purpose] This preliminary study aimed to determine the cardiorespiratory endurance of children with cerebral palsy (CP) using a case series study in order to provide the reference data required for interventions appropriate for South Korean CP sufferers, since aerobic ability evaluation and interventions for children with CP are not well recognized in South Korea. [Subjects and Methods] Four children and adolescents with CP GMFCS (Gross Motor Function Classification System) level I and II and two normally developing children (ND) (age: 7-15 years) were studied. Cycle ergometer testing was performed to determine their VO2 peak and RER peak concentrations as well as VE peak and 6MWT distance. [Results] The VO2 peak was lower in subject E (CP) at 44.5 than in subject B (ND), and it was lower in subject A (ND) at 22.9 than in subject C (CP). The 6MWT distance was longer in subjects A and B (ND) than in age-matched CP subjects. [Conclusion] This case report demonstrates that the cardiorespiratory parameters values of CP children were similar to those reported previously. Further research is required to evaluate the normative values of CP and the optimal cardiorespiratory parameters. PMID- 26157266 TI - Changes in heart-rate variability of survivors of nasopharyngeal cancer during Tai Chi Qigong practice. AB - [Purpose] To explore the changes in heart-rate variability (HRV) of survivors of nasopharyngeal cancer (NPC) before, during, and after a Tai Chi (TC) Qigong exercise. [Subjects and Methods] Eleven survivors of NPC participated voluntarily in the study. The heart rate of each participant was measured continuously for 1 minute before the TC Qigong intervention, during the 5-minute TC Qigong intervention, and for 1 minute after the intervention, using a Polar heart-rate monitor. Spectral HRV was expressed in terms of normalised low frequency (LF) power, normalised high frequency (HF) power, and the low frequency/high frequency (LF/HF) power ratio. [Results] Both the LF-power and the HF-power components had significant time effects. However, the time effect of the LF/HF power ratio was not significant. Post hoc contrast analysis revealed a significant decrease in LF power and a concomitant increase in HF power during the 4th minute and 5th minute of the TC Qigong exercise. [Conclusion] Five minutes of TC Qigong exercise was found to improve HRV by increasing HF power and decreasing LF power, but these effects were transient. TC Qigong might be an appropriate exercise for improving the ANS function and psychological and cardiac health of survivors of NPC. PMID- 26157267 TI - The effects of progressive functional training on lower limb muscle architecture and motor function in children with spastic cerebral palsy. AB - [Purpose] To investigate the effects of progressive functional training on lower limb muscle architecture and motor function of children with spastic cerebral palsy (CP). [Subjects] The subjects of this study were 26 children with spastic CP. [Methods] Thirteen subjects in the experimental group performed general neurodevelopmental treatment (NDT) and additional progressive functional trainings and 13 subjects in the control group performed only general NDT 3 times a week for 6 weeks. Ultrasonography, gross motor function measurement (GMFM) and the mobility questionnaire (MobQue) were evaluated. [Results] After the intervention, the muscle thickness of the quadriceps femoris (QF), cross sectional area of the rectus femoris (RF), pennation angle of the gastrocnemius (GCM) and the MobQue score of the experimental group were significantly greater than those of the control group. The muscle thickness of QF correlated with the cross-sectional area (CSA) of RF and the pennation angle of GCM, and GMFM score correlated with the pennation angle of GCM. [Conclusion] Progressive functional training can increase muscle thickness, CSA, and the pennation angle of the lower limb muscles, and improve the mobility of spastic CP children making it useful as a practical adjunct to rehabilitation therapy. PMID- 26157268 TI - The effects of modified constraint-induced therapy combined with mental practice on patients with chronic stroke. AB - [Purpose] The purpose of this study was to investigate the effects of the modified constraint-induced therapy (mCIT) combined with mental practice (MP) on patients with chronic stroke. [Subjects] The subjects were 26 patients with chronic stroke. [Methods] Patients were randomly assigned to the mCIMT + MP group or the MP group. All subjects were administered mCIT consisting of (1) therapy emphasizing affected arm use in functional activities 5 days/week for 6 weeks and (2) 4 hours of restraint of the less affected arm 5 days/week. The mCIT + MP subjects received 30-minute MP sessions provided directly after therapy sessions. To compare the two groups, the Action Research Arm Test (ARAT), Fugl-Meyer Assessment of Motor Recovery after stroke (FM), and Korean version of Modified Barthel Index (K-MBI) were performed. [Results] Both groups showed significant improvement in ARAT, FM, and K-MBI after the interventions. Also, there were significant difference in ARAT, FM, and K-MBI between the two groups. [Conclusion] mCIT remains a promising intervention. However, its efficacy appears to be enhanced by use of MP after mCIT clinical sessions. PMID- 26157269 TI - Effects of specific muscle imbalance improvement training on the balance ability in elite fencers. AB - [Purpose] The lunge Motion that occurs frequently in fencing training and matches results in imbalance of the upper and lower limbs muscles. This research focuses on the improvement of the imbalance that occurs in the national team fencers of the Republic of Korea through specific muscle imbalance improvement training. [Subjects] The subjects of this research were limited to right-handed male fencers. Nine male, right-handed national fencing athletes were selected for this study (4 epee, 5 sabre; age 28.2 +/- 2.2 years; height 182.3 +/- 4.0 cm; weight 76.5 +/- 8.2 kg; experience 12.4 +/- 3.0 years). [Methods] The specific muscle imbalance improvement training program was performed for 12 weeks and Pre-Post tests were to evaluate its effect on the experimental group. Measurements comprised anthropometry, test of balance, and movement analysis. [Results] After the training program, mediolateral sway of the nondominant lower limb and the balance scale showed statistically significant improvement. [Conclusion] The specific muscle imbalance improvement training program used in this research was proven to be effective for improving the muscle imbalance of elite fencers. PMID- 26157270 TI - Effect of space balance 3D training using visual feedback on balance and mobility in acute stroke patients. AB - [Purpose] The purpose of the study was to determine the effects of balance training with Space Balance 3D, which is a computerized measurement and visual feedback balance assessment system, on balance and mobility in acute stroke patients. [Subjects and Methods] This was a randomized controlled trial in which 52 subjects were assigned randomly into either an experimental group or a control group. The experimental group, which contained 26 subjects, received balance training with a Space Balance 3D exercise program and conventional physical therapy interventions 5 times per week during 3 weeks. Outcome measures were examined before and after the 3-week interventions using the Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and Postural Assessment Scale for Stroke Patients (PASS). The data were analyzed by a two-way repeated measures ANOVA using SPSS 19.0. [Results] The results revealed a nonsignificant interaction effect between group and time period for both groups before and after the interventions in the BBS score, TUG score, and PASS score. In addition, the experimental group showed more improvement than the control group in the BBS, TUG and PASS scores, but the differences were not significant. In the comparisons within the groups by time, both groups showed significant improvement in BBS, TUG, and PASS scores. [Conclusion] The Space Balance 3D training with conventional physical therapy intervention is recommended for improvement of balance and mobility in acute stroke patients. PMID- 26157271 TI - The Mulligan ankle taping does not affect balance performance in healthy subjects: a prospective, randomized blinded trial. AB - [Purpose] The aim of this study was to evaluate the immediate effects of Mulligan fibular taping on static and dynamic postural balance in healthy subjects using computerized dynamic posturography (CDP). [Subjects and Methods] Forty-four volunteers (26 males and 18 females) aged 21 +/-2 years participated in the study. The Mulligan tape was applied by a specialist in this technique. The placebo group received a treatment with a similar tape but with several cuts to avoid the fibular repositioning effect produced by Mulligan tape. MAIN OUTCOME MEASURES: The Sensory Organization Test (SOT) and the Motor Control Test (MCT) were performed by each subject at baseline and after the interventions. Outcome measures included equilibrium and strategy scores from each trial and condition of the SOT, and speed of reaction (latency period) from the MCT. [Results] Mulligan ankle taping did not have an impact on postural control during static and dynamic balance in subjects with healthy ankles when compared with placebo taping. [Conclusion] There was no difference in, equilibrium and strategy (SOT) and speed of reaction (MCT) in any of the subjects in this study. Therefore, this study suggests that Mulligan ankle taping does not have an impact on balance in healthy subjects. PMID- 26157272 TI - Effects of conventional overground gait training and a gait trainer with partial body weight support on spatiotemporal gait parameters of patients after stroke. AB - [Purpose] The purpose of this study was to confirm the effects of both conventional overground gait training (CGT) and a gait trainer with partial body weight support (GTBWS) on spatiotemporal gait parameters of patients with hemiparesis following chronic stroke. [Subjects and Methods] Thirty stroke patients were alternately assigned to one of two treatment groups, and both groups underwent CGT and GTBWS. [Results] The functional ambulation classification on the affected side improved significantly in the CGT and GTBWS groups. Walking speed also improved significantly in both groups. [Conclusion] These results suggest that the GTBWS in company with CGT may be, in part, an effective method of gait training for restoring gait ability in patients after a stroke. PMID- 26157273 TI - The effects of cervical joint manipulation, based on passive motion analysis, on cervical lordosis, forward head posture, and cervical ROM in university students with abnormal posture of the cervical spine. AB - [Purpose] The aim of this study was to determine the effect of cervical posture manipulation, based on passive motion analysis (MBPMA) and general mobilization, on cervical lordosis, forward head posture (FHP), and cervical ROM in university students with problems in cervical posture and range of motion (ROM). [Subjects] The Subjects were 40 university students in their 20s who displayed problems in cervical posture and ROM; they were divided into an MBPMA group (n=20) and a mobilization group (n=20). [Methods] Each group underwent MBPMA or mobilization three times a week for four weeks. The effects of MBPMA and mobilization on cervical lordosis, FHP, and cervical ROM were analyzed by radiography. [Results] MBPMA was effective in increasing the cervical lordosis, cervical extension ROM (CER), and ranges of flexion and extension motion (RFEM) and in decreasing FHP. Mobilization was effective in increasing CER and decreasing FHP. [Conclusion] MBPMA can be utilized as an effective method for decreasing FHP and improving cervical lordosis and cervical ROM. PMID- 26157274 TI - Effects of running in place accompanied by abdominal drawing-in on the posture of healthy adults. AB - [Purpose] This study aimed to determine the effect of running in place accompanied by abdominal drawing-in on the posture of healthy adults. [Subjects] A total of 30 subjects were divided into a training group and a control group, each containing 15 subjects. [Methods] The training group performed running in place accompanied by abdominal drawing-in for 30 min daily, three times a week for six weeks. Trunk inclination (TIN), trunk imbalance (TIM), pelvic position (PPO), pelvic torsion (PTO), pelvic rotation (PRO), and position of the scapulae (PSA) were assessed using BackMapper for both the training group and the control group before and after the experiment. [Results] Comparison of the results of the training and control groups before and after the experiment showed that the training group had statistically significant changes in TIN, TIM, PPO, PTO, and PSA, while the control group had no statistically significant changes in any items. [Conclusion] Running in place can be conveniently utilized by students or workers, regardless of time and place, as an exercise for postural improvement. PMID- 26157275 TI - Upper limb function evaluation scales for individuals with cerebral palsy: a systematic review. AB - [Purpose] The aim of the present study was to perform a systematic review of the literature on the scales and methods most often used for the evaluation of upper limb function in individuals with cerebral palsy. [Materials and Methods] Searches were conducted in the Medline, PEDro, Lilacs, Scielo, and PubMed databases. The following inclusion criteria were used for the selection of articles: randomized controlled study, evaluation of upper limb function in individuals with cerebral palsy, and publication between 2006 and 2014. The methodological quality of the articles was evaluated using the PEDro evidence scale. [Results] Five articles met the inclusion criteria and achieved 6 points or higher on the PEDro scale of methodological quality. [Conclusion] The studies analyzed used different evaluation scales, but no consensus has been reached thus far on which scale is the most appropriate. Thus, further studies are needed to establish an adequate method for the evaluation of upper limb function in individuals with cerebral palsy. PMID- 26157276 TI - Physical therapy education in Saudi Arabia. AB - [Purpose] To review the physical therapy educational program model, professional curriculum, and gender representation at major universities, as well as the quality and scope of physical therapy practice in Saudi Arabia. [Methods] Information regarding course curriculum, gender representation, and the quality and scope of physical therapy practice was collected from six universities in Saudi Arabia, the Saudi Physical Therapy Association, and the Saudi Health Commission. [Results] The first bachelor's degree course of physical therapy was started in Saudi Arabia more than 30 years ago. In the last 10 years, the number of universities offering a bachelor's degree in physical therapy has risen from 6 to 16, of which 14 are governmental and two are private. The 5- to 6 year bachelor's degree program in physiotherapy includes an internship and preparatory prerequisite courses. Postgraduate study in physical therapy was introduced in 2000. Most universities offer segregated physical therapy courses for male and female students. [Conclusion] The enrollment of students in physical therapy programs in Saudi Arabia is gradually increasing. There are many opportunities to extend the scope of practice and contribute to the health needs of the Arab population and international communities. PMID- 26157277 TI - Coexistence of osteopoikilosis with seronegative spondyloarthritis and spinal stenosis. AB - [Purpose] Osteopoikilosis is a rare hereditary bone disease that is usually asymptomatic. It is generally diagnosed incidentally on plain radiography. The coexistence of osteopoikilosis with seronegative spondyloarthritis or spinal stenosis is rarely reported. Here, we report the case of a 27-year-old male patient with osteopoikilosis, seronegative spondyloarthritis, and spinal stenosis. [Subject] A 27-year-old male patient with buttock pain and back pain radiating to the legs. [Methods] A plain anteroposterior radiograph of the pelvis revealed numerous round and oval sclerotic bone areas of varying size. Investigation of the knee joints showed similar findings, and the patient was diagnosed with osteopoikilosis. Lumbar magnetic resonance images showed spinal stenosis and degenerative changes in his lumbar facet joints. Magnetic resonance images of the sacroiliac joints showed bilateral involvement with narrowing of both sacroiliac joints, nodular multiple sclerotic foci, and contrast enhancement in both joint spaces and periarticular areas. HLA B-27 test was negative. [Results] The patient was diagnosed with osteopoikilosis, seronegative spondyloarthritis, and spinal stenosis. Treatment included asemetasin twice daily and exercise therapy. [Conclusion] Symptomatic patients with osteopoikilosis should be investigated for other possible coexisting medical conditions; this will shorten the times to diagnosis and treatment. PMID- 26157278 TI - Effect of joint mobilization using KEOMT and PNF on a patient with CLBP and a lumbar transitional vertebra: a case study. AB - [Purpose] The purpose of this case study was to identify the effects of joint mobilization using Kaltenborn-Evjenth orthopedic manual therapy (KEOMT) and proprioceptive neuromuscular facilitation (PNF) techniques on a patient with chronic low back pain (CLBP) and a lumbar transitional vertebra. [Methods] The intervention methods were joint mobilization using KEOMT and PNF techniques. The program consisted of 40-min sessions 3 days a week for 4 weeks. The spinal motion (thoracic and lumbar vertebrae), pain, and thickness of the multifidus were measured. [Results] The angle of spinal curvature increased, and the range of motions (ROMs) flexion and extension increased in the thoracic and lumbar vertebrae. The pain score as measured on a visual analogue scale (VAS) and the Oswestry disability index (ODI) score decreased. The thickness of the multifidus (L4) increased on the left and right sides. [Conclusion] These results suggest that joint mobilization using KEOMT and PNF techniques had a positive effect on the spinal motion, pain, and thickness of the multifidus of a patient with chronic low back pain and a lumbar transitional vertebra. PMID- 26157279 TI - A novel objective evaluation method for trunk function. AB - [Purpose] To investigate whether an objective evaluation method for trunk function, namely the "trunk righting test", is reproducible and reliable by testing on different observers (from experienced to beginners) and by confirming the test-retest reliability. [Subjects] Five healthy subjects were evaluated in this correlation study. [Methods] A handheld dynamometer was used in the assessments. The motor task was a trunk righting motion by moving the part with the sensor pad 10 cm outward from the original position. During measurement, the posture was held at maximum effort for 5 s. Measurement was repeated three times. Interexaminer reproducibility was examined in two physical therapists with 1 year experience and one physical therapist with 7 years of experience. The measured values were evaluated for reliability by using intraclass correlation coefficients (ICC 1.1) and interclass correlation coefficients (ICC 2.1). [Results] The test-retest reliability ICC 1.1 and ICC 2.1 were all high. The ICC 1.1 was >0.90. The ICC 2.1 was 0.93. [Conclusion] We developed the trunk righting test as a novel objective evaluation method for trunk function. As the study included inexperienced therapists, the results suggest that the trunk righting test could be used in the clinic, independent of the experience of the therapists. PMID- 26157280 TI - Pancreatic cancer - lessons from the past decade. PMID- 26157281 TI - Prophylactic cranial irradiation in breast cancer: A new way forward. PMID- 26157282 TI - Indian Council of Medical Research consensus document for the management of gall bladder cancer. AB - The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.All postcholecystectomy gallbladder specimens should be opened and examined carefully by the operating surgeon and be sent for histopathological examination.All "incidental" gall bladder cancers (GBCs) picked up on histopathological examination should have an expert opinion.Evaluation of a patient with early GBC should include essential tests: A computed tomography (CT) scan (multi-detector or helical) of the abdomen and pelvis for staging with a CT chest or chest X-ray, and complete blood counts, renal and liver function tests. magnetic resonance imaging/positron emission tomography (PET)-CT are not recommended for all patients.For early stage disease (up to Stage IVA), surgery is recommended. The need for adjuvant treatment would be guided by the histopathological analysis of the resected specimen.Patients with Stage IVB/metastatic disease must be assessed for palliative e.g. endoscopic or radiological intervention, chemotherapy versus best supportive care on an individual basis. These patients do not require extensive workup outside of a clinical trial setting.There is an urgent need for multicenter trials from India covering various aspects of epidemiology (viz., identification of population at high-risk, organized follow-up), clinical management (viz., bile spill during surgery, excision of all port sites, adjuvant/neoadjuvant therapy) and basic research (viz., what causes GBC). PMID- 26157283 TI - The fight against cancer: Is it worthwhile? AB - This article alludes to the findings of Tomasetti and Vogelstein and argues that for clinicians and scientists no matter how difficult understanding the pathogenesis of cancer may be, they remain the only hope for patients suffering from the disease. Data citing wide differences in cancer incidence in different parts of the world is presented to drive home the point that 'Bad luck' is not a good enough explanation for cancer pathogenesis. There remains a lot to be uncovered in cancer and clinicians and scientists should strive to this end. PMID- 26157284 TI - Management of solitary and multiple brain metastases from breast cancer. AB - As local and systemic control of breast cancer improves, metastasis to the brain remains a common event requiring a specialized management approach. Women diagnosed with breast cancer who develop brain metastases have superior overall survival compared to patients with other forms of metastatic carcinoma. This article summarizes some of the unique aspects of care for patients with breast cancer metastases to the brain. PMID- 26157285 TI - The changing nature of end of life care. AB - Good end of life care (EOLC) for patients with incurable cancer is becoming a greater priority for oncologists in recent years. Frameworks such as the Liverpool Care Pathway (LCP) have often been helpful in guiding good care at the end of life. However, in the past year, the LCP has been phased out of use in the United Kingdom (UK), following concerns that it was poorly implemented. This review describes the LCP's origins in the UK, its strengths and limitations, and the concerns that prompted a review of its use. It describes the recommendations for change made by an independent review, and the alternative strategies now being developed in the UK to guide good EOLC. Although the LCP is still being widely used worldwide, the lessons learned from the UK can be widely applied in other countries. PMID- 26157286 TI - Outcomes of pediatric glioblastoma treated with adjuvant chemoradiation with temozolomide and correlation with prognostic factors. AB - BACKGROUND: Pediatric glioblastoma (pGBM) patients are underrepresented in major trials for this disease. We aimed to explore the outcome of pGBM patients treated with concurrent and adjuvant temozolomide (TMZ). MATERIALS AND METHODS: 23 patients of pGBM treated from 2004 to 2010 were included in this retrospective analysis. Adjuvant therapy included conformal radiation 60 gray at 2 gray/fraction daily over 6 weeks with concurrent TMZ 75 mg/m(2) followed by six cycles of adjuvant TMZ 150-200 mg/m(2) (day 1-5) every 4 weeks. Kaplan-Meier estimates of overall survival (OS) were determined. Univariate analysis with log rank test was used to determine the impact of prognostic variables on survival. RESULTS: Median age at presentation was 11.5 years (range: 7-19 years) and M:F ratio was 15:8. All patients underwent maximal safe surgical resection; 13 gross total resection and 10 sub-total resection. At a median follow-up of 18 months (range: 2.1-126 months), the estimated median OS was 41.9 months. The estimated median OS for patients receiving only concurrent TMZ was 8 months while that for patients receiving concurrent and adjuvant TMZ was 41.9 months (P = 0.081). Estimated median OS for patients who did not complete six cycles of adjuvant TMZ was 9.5 months versus not reached for those who completed at least six cycles (P = 0.0005). Other prognostic factors did not correlate with survival. CONCLUSIONS: Our study shows the benefit of TMZ for pGBM patients. Both concurrent and adjuvant TMZ seem to be important for superior OS in this group of patients. PMID- 26157287 TI - Knowledge, attitudes and practice toward cervical cancer screening among Sikkimese nursing staff in India. AB - OBJECTIVES: To assess baseline knowledge of cancer cervix, screening and practice of Pap smear screening among Sikkimese staff nurses in India. MATERIALS AND METHODS: Between April 2012 and February 2013, a predesigned, pretested, self administered multiple responses questionnaire survey was conducted among staff nurses' working in various hospitals of Sikkim. Questionnaire contained information about their demographics, knowledge of cervical cancer, its risk factors, screening methods, attitudes toward cervical cancer screening and practice of Pap smear amongst themselves. RESULTS: Overall, 90.4% nurses responded that they were aware of cancer cervix. Three quarter of the staff nurses were not aware of commonest site being cancer cervix in women. Of the 320 participants, who had heard of cancer cervix, 253 (79.1%) were aware of cancer cervix screening. Pap smear screening should start at 21 years or 3 years after sexual debut was known to only one-third of the nursing staff. Age was found to be a significant predictor of awareness of Pap smear screening among nursing staff. Awareness was significantly more prevalent among older staff (P < 0.007). Married nursing staffs were significantly more likely to be aware of screening methods, and nursing staff of Christian and Buddhist religion were 1.25 times and 2.03 times more likely to aware of screening methods than Hindu religion respectively. Only 16.6% nurses, who were aware of a Pap smear (11.9% of the total sample), had ever undergone a Pap smear test. Most common reason offered for not undergoing Pap smear test were, they felt they were not at risk (41%), uncomfortable pelvic examination (25%) and fear of a bad result (16.6%). CONCLUSION: Knowledge of cancer cervix, screening and practice of Pap smear was low among Sikkimese nursing staff in India. There is an urgent need for re orientation course for working nurses and integration of cervical cancer prevention issues in the nurses' existing curriculum in India and other developing countries. PMID- 26157288 TI - Transforming growth factor-beta1 and TGF-beta2 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation. AB - BACKGROUND AND OBJECTIVES: Oral Submucous Fibrosis (OSF) is a potentially malignant oral disorder which leads to fibrosis of the oral mucosa and has a high rate of malignant transformation. The consumption of various forms of areca nut is causatively linked to the condition. The constituents of areca nut activate several pro-fibrotic cytokines, chiefly transforming growth factor-beta1, beta2, which leads to an increased deposition and decreased degradation of extracellular matrix and collagen. TGF-beta1, beta2 probably represent the major pathway in the deposition of collagen fibres in this condition. The present study aims to identify and correlate the expressions of TGF-beta1 and TGF-beta2 immunohistochemically on paraffin sections of various stages of OSF. A comparison was also made between normal oral mucosa and scar tissue and OSF to judge the mode, extent and type of expression of TGF beta1, beta2. METHODS: The expression of TGF-beta1 antibody (8A11, NovusBio, USA) and TGF-beta2 antibody (TB21, NovusBio, USA) was detected immunohistochemically on paraffin sections of 58 and 70 cases of OSF respectively, 10 cases of normal oral mucosal tissue and 4 cases of scar tissue. A mapping of the positivity of the two cytokines was done using JenOptik camera and ProReg image analysis software. The results were statistically analysed using one way ANOVA and students "t" test. RESULTS: Expression of TGF-beta1 and TGF-beta2 was more in OSF as compared with normal oral mucosa, scar/keloid tissue showing highest values. Positivity for both the markers was seen in epithelium, around the blood vessels, in areas of inflammatory infiltrate, fibroblasts and in muscles. TGF-beta1 expression was higher and more intense than that of TGF-beta2 in all the cases. TGF-beta2 was restricted in its expression to submucosal area with minimal involvement of the epithelium and the deeper muscle tissue. CONCLUSION: TGF-beta1 is the most prominent cytokine in the fibrotic pathway and TGF-beta2 plays a contributory role. PMID- 26157289 TI - Hormone receptor status (estrogen receptor, progesterone receptor), human epidermal growth factor-2 and p53 in South Indian breast cancer patients: A tertiary care center experience. AB - Breast cancer, in India, is the second commonest cancer in females. Receptor status with ER/PR/Her 2 is now routinely done in patients with invasive carcinoma. The tumour suppressor gene, p53, is also present in most breast cancers. Proteins produced by a mutated p53 gene, accumulate in the nucleus of tumour cells and are detected by immunohistochemistry (IHC). We have undertaken this study with the aim to evaluate the ER, PR, HER-2 and p53 expressions in invasive breast carcinomas by IHC and to compare the HER-2 expression with various clinicopathological parameters. MATERIALS AND METHODS: In this retrospective single institutional study from January 2001 to December 2010, 389 cases of histopathologically diagnosed infiltrating carcinoma of breast were evaluated taking into account various parameters like age, tumour size, grade, lymph node involvement, ER and PR. HER-2 and p53 was done in 352 cases. RESULTS: The age range was 23-90 years with a mean of 50.7 years. Majority of tumours were T2 (79.6%) and Grade II (60.9%). Our data showed overall 47.6% ER, 48.8% PR, 29.6% HER-2 and 69.2% p53 positivity. There was no significant correlation between HER-2 and age, tumour size, lymph node status, ER, and PR. There was significant correlation between HER-2 and tumour grade (P = 0.031), p53 (P < 0.001). There was no inverse correlation between HER-2 and combined ER, PR status. Triple-negative breast cancers which constituted 22.7% of our cases did not reveal any correlation with various parameters. CONCLUSION: In our study, ER status was low, and incidence of p53 was high. These findings suggest that many of the tumours in Indian females may be of an aggressive type, and novel treatment approaches may be tried. We conclude that the assessment of all four markers is desirable. PMID- 26157290 TI - Role of triple test score in the evaluation of palpable breast lump. AB - INTRODUCTION: Fine-needle aspiration cytology (FNAC) method is safe, reliable and time saving outdoor procedure with little discomfort to the patient for detecting Carcinoma breast. The efficacy can further be enhanced when physical breast examination, mammography and FNAC (the triple test [TT]) are jointly taken into consideration. AIMS AND OBJECTIVES: The aim was to evaluate the role of TT score (TTS) in palpable breast masses. MATERIALS AND METHODS: This prospective study was carried out from May 2010 to April 2012. In the subjects referred to the Department of Pathology for FNAC of the breast mass, the TTS was calculated, and histopathological findings were noted. RESULTS: In the study period TTS score was calculated in 200 cases out of 225 FNAC's of breast. Of 124 benign cases on cytology, only three showed discordant TTS. Out of 62 malignant cases, 61 showed concordant TTS and one case of mastitis on histopathology showed TTS of five. Out of all the benign lesions, two cases of fibrocystic disease and a single case of phylloides tumor gave a TTS >=6. These cases were diagnosed as infiltrating ductal carcinoma and angiosarcoma respectively on histopathology. Histopathological correlation was possible in only 70 patients. Of these 70, 28 were from the benign category and 42 were from the malignant category. TTS of >=6 has a sensitivity of 97.44%, specificity of 100%. FNAC has a sensitivity of 88.37%, specificity of 96.42%. CONCLUSIONS: TT reliably guides evaluation of palpable breast masses. Histological correlation indicated TTS to be better diagnostic tool than FNAC alone. PMID- 26157291 TI - Delivery of cancer care in rural India: Experiences of establishing a rural comprehensive cancer care facility. PMID- 26157292 TI - Excellent response to oral Metronomic chemotherapy in unresectable adenocarcinoma of external auditory canal. PMID- 26157293 TI - Updates from Gastrointestinal ASCO 2015. AB - This year at ASCO GI we saw important data presented that has continued to shape the way we treat GI malignancies. Several important questions were addressed. Can we avoid surgery among patients with rectal tumors? Data from a provocative retrospective study indicated that certain subgroups of patients might not need surgery thereby preserving the rectum without compromising survival outcome. What is the role of ramicurumab among patients with advanced colorectal cancers? Data from the phase III RAISE trial revealed that the addition of ramicurumab to second line therapy significantly improved median overall survival. What is the role of immunotherapy in GI malignancies? Interesting results from the KEYNOTE 012 trial was presented that looked at the efficacy of pembriluzumab among patients with advanced gastric cancer with the investigators reporting interesting results of an objective response rate of 22.1% and a 6 months progression free survival of 24%. In this review we will briefly present these and other important highlights of the ASCO GI meeting. PMID- 26157294 TI - From the Editor's desk. PMID- 26157295 TI - Sperm function test. AB - With absolute normal semen analysis parameters it may not be necessary to shift to specialized tests early but in cases with borderline parameters or with history of fertilization failure in past it becomes necessary to do a battery of tests to evaluate different parameters of spermatozoa. Various sperm function tests are proposed and endorsed by different researchers in addition to the routine evaluation of fertility. These tests detect function of a certain part of spermatozoon and give insight on the events in fertilization of the oocyte. The sperms need to get nutrition from the seminal plasma in the form of fructose and citrate (this can be assessed by fructose qualitative and quantitative estimation, citrate estimation). They should be protected from the bad effects of pus cells and reactive oxygen species (ROS) (leukocyte detection test, ROS estimation). Their number should be in sufficient in terms of (count), structure normal to be able to fertilize eggs (semen morphology). Sperms should have intact and functioning membrane to survive harsh environment of vagina and uterine fluids (vitality and hypo-osmotic swelling test), should have good mitochondrial function to be able to provide energy (mitochondrial activity index test). They should also have satisfactory acrosome function to be able to burrow a hole in zona pellucida (acrosome intactness test, zona penetration test). Finally, they should have properly packed DNA in the nucleus to be able to transfer the male genes (nuclear chromatic decondensation test) to the oocyte during fertilization. PMID- 26157296 TI - Understanding normal development of adolescent sexuality: A bumpy ride. AB - Adolescence, derived from the Latin word "adolescere" meaning "to grow up" is a critical developmental period. During adolescence, major biological as well as psychological developments take place. Development of sexuality is an important bio-psycho-social development, which takes an adult shape during this period. During adolescence, an individual's thought, perception as well as response gets colored sexually. Puberty is an important landmark of sexuality development that occurs in the adolescence. The myriad of changes that occurs in adolescents puts them under enormous stress, which may have adverse physical, as well as psychological consequences. Understanding adolescent sexuality has important clinical, legal, social, cultural, as well as educational implications. PMID- 26157297 TI - Factors associated with nonresponse to ovulation induction using letrozole among women with World Health Organization group II anovulation. AB - CONTEXT: Letrozole, a third generation aromatase inhibitor is gaining importance in ovulation induction. Some prefer to use it as a second line agent in women who fail to respond to clomifene citrate. However, our knowledge about the predictors of response to letrozole is limited. AIMS: The study was aimed at identifying the factors associated with letrozole resistance among women with World Health Organization (WHO) group II anovulation. SUBJECTS AND METHODS: Study was conducted at the infertility clinic at a tertiary care hospital in Sri Lanka. A case-control study design was used and included 50 subjects with WHO group II anovulation (25 clomifene responsive and 25 clomifene resistant). After a treatment cycle of letrozole, the factors were compared between the subjects who responded and those who failed to respond to treatment. RESULTS: Ovulation was achieved in 76% (n = 19) of subjects who had responded to clomifene previously and in 24% (n = 6) with clomifene resistance. The factors associated with letrozole resistance included the presence of hirsutism (odds ratio [OR]: 3.89; 95% confidence interval [CI]: 1.2-12.3) and clomifene resistance (OR: 10.03; 95% CI: 2.81-35.7). The early follicular phase mean (standard deviation) luteinizing hormone level was significantly higher among the nonresponders (9.75 [4.78] - 7.28 [2.3]; P = 0.02). Nonresponders showed significantly lower levels of oestradiol on the 5(th) and 9(th) days (28.50 [3.39] pg/mL vs. 7.49 [3.62] pg/mL; P = 0.0007 and 142.04 [76.22] pg/mL vs. 28.10 [12.8] pg/mL; P = 0.0001) of the menstrual cycle, respectively. CONCLUSIONS: The features associated with resistance to Letrozole at a dose of 2.5 mg show some overlap with those associated with clomifene resistance. However, some features do not show similar association. The effectiveness of letrozole at a dose of 2.5 mg in induction of ovulation among women with clomifene resistance is low and it does not seem to be a suitable treatment at a dose of 2.5 mg for this indication. PMID- 26157298 TI - Do increased levels of progesterone and progesterone/estradiol ratio on the day of human chorionic gonadotropin affects pregnancy outcome in long agonist protocol in fresh in vitro fertilization/intracytoplasmic sperm injection cycles? AB - BACKGROUND: The effect of elevated levels of serum progesterone (P4) and estradiol (E2) on the day of human chorionic gonadotropin and their cut-off value on in vitro fertilization (IVF) outcomes is still not clear. AIMS: The aim was to evaluate the association between serum P4, E2 and progesterone/estradiol ratio (P4/E2) on pregnancy outcome in IVF/intracytoplasmic sperm injection (ICSI) cycles with long agonist protocol. SETTING AND DESIGN: Retrospective, single center, cohort study. MATERIALS AND METHODS: A review of complete data of 544 women undergoing fresh IVF/ICSI cycles (539 cycles) with long agonist protocol from January 2012 to February 2014 was done. Data were stratified into Three groups according to the number of oocytes retrieved: low (<=4 oocytes obtained), intermediate (5-19 oocytes obtained), and high ovarian response (>=20 oocytes obtained). STATISTICAL ANALYSIS: Fishers exact test/Chi-square was carried for comparing categorical data. Receiver operating characteristics analysis was performed to determine the cut-off value for P4 and P4/E2 detrimental for pregnancy. RESULTS: A negative association was observed between pregnancy rate (PR) and serum P4 and P4/E2 levels with no effect on fertilization and cleavage rate. The overall cut-off value of serum P4 and P4/E2 ratio detrimental for pregnancy was found to be 1.075 and >=0.35, respectively. Different P4 threshold according to the ovarian responders were calculated, 1.075 for intermediate and 1.275 for high responders. Serum E2 levels were not found to be significantly associated with PR. CONCLUSION: Serum P4 levels and P4/E2 ratio are a significant predictor for pregnancy outcome without affecting cleavage and fertilization rate while serum estradiol levels do not seem to affect PR. PMID- 26157299 TI - Impact of different controlled ovarian stimulation protocols on the physical and psychological burdens in women undergoing in vitro fertilization/intra cytoplasmic sperm injection. AB - CONTEXT: Infertility treatment involves a considerable amount of physical and psychological burden which may impact the outcome. AIM: The objective was to understand the amount of physical and psychological burden in women undergoing their first in vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI) cycles. SETTING AND DESIGN: Multi-center, prospective, parallel, observational study. MATERIALS AND METHODS: The study was conducted across 12 IVF centers in India. A total of 692 women undergoing controlled ovarian stimulation as a part of the first cycle IVF/ICSI completed the trial. Women were recruited in 2 groups based on type of treatment (Group A - gonadotropin-releasing hormone [GnRH] antagonist; Group B - GnRH agonist) and were asked to fill questionnaires during the 2 treatment visits. RESULTS: The mean changes between Visit 1 (baseline) and Visit 2 in anxiety and depression (Hospital Anxiety and Depression Scale) scores in Group A for anxiety and depression were -0.5 (3.67), -0.1 (3.57) respectively and for Group B were -0.4 (3.68), 0.1 (3.67) respectively, which was not statistically significant. In Group A, the mean (+/-standard deviation [SD]) Hopkins Symptom Check List (HSCL) score was 17.9 (+/-5.17) in visit 1 and 19.1 (+/-5.45) Visit 2. The change between visits was 1.1 (P < 0.0001) with higher score reflecting higher somatic distress symptoms. In Group B, the mean (+/-SD) HSCL score was 18.2 (+/-5.19) in Visit 1 and 18.8 (+/-5.23) in visit 2. The change between visits was 0.6 (P < 0.0014). The difference of the mean change in physical burden between Group A and Group B was not statistically significant. CONCLUSION: A significant impact in both treatment protocols with respect to the physical burden was found between Visit 1 and Visit 2 but no difference in physical or psychological burden between the two treatment groups was observed. PMID- 26157300 TI - Hematocrit as a simple method to predict and manage ovarian hyperstimulation syndrome in assisted reproduction. AB - AIM: The aim was to analyze the hematocrit levels in cases of ovarian hyperstimulation syndrome (OHSS), syndrome occurring during in-vitro fertilization (IVF), and study its role as a prognostic indicator. SUBJECTS AND METHODS: Two years data of 66 women at high risk for developing OHSS was analyzed. Twenty-seven women who developed OHSS were further analyzed based on their hematocrit levels on the day of oocyte pick-up (OPU) and the day of embryo transfer (ET) to see if there was a prognostic trend. RESULTS: Of the total 225 IVF cases, 66 were deemed high risk for developing OHSS. Twenty-seven of these developed OHSS (40.9%). Of these 27, 21 (77.8%) had a hematocrit >35% on the day of OPU. The mean hematocrit in women developing OHSS on the day of OPU was 37.39% (standard deviation [SD] 2.66) as against 35.97% (2.80) in those not developing OHSS. This difference was statistically significant (P = 0.043). On the day of ET, 23/27 (85.8%) who developed OHSS had a hematocrit of >35%. The mean hematocrit was 39.29% (SD 3.85) in those who developed OHSS as against 34.7% (2.88) in those who did not. This difference (4.85) was statistically significant (P < 0.001). CONCLUSIONS: Women undergoing IVF were at a higher risk of developing OHSS when their hematocrit on the day of OPU and ET was >35%. Those who required cancellation of ET had a hematocrit of >35% on the day of ET or showed a significant increase of 3% from OPU to ET. PMID- 26157301 TI - Oocyte retrieval at 140-mmHg negative aspiration pressure: A promising alternative to flushing and aspiration in assisted reproduction in women with low ovarian reserve. AB - BACKGROUND: Oocyte retrieval in women with low ovarian reserve is challenging and often results in poor pregnancy outcomes. AIM: The aim was to compare outcomes of oocyte retrieval using three aspiration methods in women with normal and low antral follicle counts (AFCs). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. MATERIALS AND METHODS: Data from 172 women who underwent in-vitro fertilization/intracytoplasmic sperm injection over 3 years was studied after dividing into three groups: Group A (96) - normal AFC (>=10), direct oocyte retrieval at 120 mmHg, Group B (41) - low AFC (<10), direct retrieval at 140 mmHg, Group C (35) - low AFC, follicular flushing, and aspiration at 120-mmHg. In each group, oocyte yield, embryo quality, and pregnancy out comes were assessed. RESULTS: The oocyte and embryo yield in Groups A and B were comparable (P > 0.05) but were significantly less in Group C (P < 0.05). The pregnancy rates in Groups A and B were similar (35.4%, 39%) but were significantly less (17.1%) in Group C (P < 0.05). The live birth rate was 76% in Group A, 69% in Group B, and 50% in Group C. The miscarriage rates in the three groups were 21%, 31%, and 50%, respectively. CONCLUSION: Direct oocyte retrieval with 140-mmHg showed significantly better oocyte yield and pregnancy outcomes compared to flushing and aspiration in women with low AFC. PMID- 26157303 TI - Hypoactive sexual desire disorder caused by antiepileptic drugs. AB - Female sexual dysfunction is common but poorly understood sexual problem in women. Sexual dysfunction in female is multi-factorial in origin and also observed with intake of drug acting on central nervous system. This case report describes a female epileptic patient who developed sexual dysfunction with intake of antiepileptic drugs. PMID- 26157302 TI - Adipose tissue-derived mesenchymal stem cells repair germinal cells of seminiferous tubules of busulfan-induced azoospermic rats. AB - CONTEXT: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are less invasive than bone marrow mesenchymal stem cells to obtain for cell therapy. AIMS: The aims of this study were to evaluate the germinal cells characteristics and repairs in seminiferous tubules of busulfan-induced azoospermic rats after AT MSCs transplantation. SETTINGS AND DESIGN: Experimental case-control study. MATERIALS AND METHODS: In the present experimental study, donors AT-MSCs were isolated from subcutaneous adipose tissue of two Sprague-Dawley rats. The recipients (n = 5) were received two doses of 10 mg/kg of busulfan with 21 days interval to stop endogenous spermatogenesis. After induction of azoospermia by busulfan, rats were injected with the AT-MSCs into the efferent duct of right testes. After 60 days, the right testes were injected AT-MSCs were compared to left azoospermic testes. Five untreated male rats served as negative control. STATISTICAL ANALYSIS USED: Stereological indices were analyzed by one-way ANOVA and LSD post-hoc test. The spermatogenesis index was compared using Mann-Whitney U test. RESULTS: After stereological analyses, the seminiferous tubules treated with AT-MSCs had normal morphology. The untreated seminiferous tubules were empty. Spermatogenesis was observed in most cell-treated seminiferous tubules. CONCLUSIONS: The testis of busulfan-induced azoospermic rats accepted transplanted AT-MSCs. The transplanted AT-MSCs could induce spermatogenesis in seminiferous tubules of the rat. PMID- 26157304 TI - Novel balanced chromosomal translocations in females with recurrent spontaneous abortions: Two case studies. AB - Two couples with a history of recurrent pregnancy losses were referred to the Institute of Genetic Medicine and Genomic Science for cytogenetic evaluation. Chromosomal analysis of the phenotypically normal couples was done to investigate whether there are any new chromosomal abnormalities present in either of the couples caused recurrent pregnancy losses. Clinical and hormonal profile of the couples revealed normal parameters. The ultrasound scan of the females showed normal uterine and ovarian structures. Chromosomal analysis of the couples revealed normal 46, XY karyotypes in the both the male partners, and novel balanced reciprocal translocations 46, XX, t (5;8) (q35.3;q24.23) and 46, XX, t (4;13) (q12;q14) chromosomal constitutions in the female partners. Further, corroboration of the chromosome abnormalities was carried out by high resolution banding analysis. Unique and novel balanced reciprocal translocations were reported as an original investigation in two female partners from two different unrelated families both with the history of recurrent pregnancy losses. PMID- 26157305 TI - Changing Skin Color. PMID- 26157306 TI - Role of Recipient-site Preparation Techniques and Post-operative Wound Dressing in the Surgical Management of Vitiligo. AB - Vitiligo is an acquired skin disorder characterized by the destruction of melanocytes resulting in achromic macules and patches involving the affected skin. Multiple methods of treatments have emerged to manage vitiligo, including medical and surgical techniques. Among the surgical techniques described in the management of vitiligo are minipunch grafting, split-thickness skin grafting, hair follicle transplantation, suction blister grafting, and cultured and non cultured autologous melanocyte transplantation. However, prior to grafting optimal recipient-site preparation is needed for graft survival and successful repigmentation outcomes. Similarly, post-operative care of the recipient site is vital to yielding a viable graft irrespective of the transplantation technique employed. This article reviews the multiple methods employed to prepare the recipient site in vitiligo surgeries and the post-surgical conditions which optimize graft viability. A pubmed search was conducted utilizing the key words listed below. PMID- 26157307 TI - Photodynamic Therapy Followed by Mohs Micrographic Surgery Compared to Mohs Micrographic Surgery Alone for the Treatment of Basal Cell Carcinoma: Results of a Pilot Single-Blinded Randomised Controlled Trial. AB - INTRODUCTION: Basal cell carcinoma is a common cutaneous malignant tumour. Surgical excision is the "gold standard" treatment for most subtypes, with Mohs micrographic surgery (MMS) offering the highest cure rate. Other treatment modalities used include photodynamic therapy (PDT). BACKGROUND: We aimed to study the efficacy of combining MMS with PDT to see whether this would reduce the number of stages and final defect size when compared with MMS alone. MATERIALS AND METHODS: Our study was a single-centre, single-blinded, randomised and controlled pilot study involving a total of 19 patients. Nine patients were randomised to pre-treatment with PDT followed by MMS of whom two withdrew; the remaining 10 patients were randomised to the MMS alone. Follow-up visits were arranged at 3 and 6 months post-surgery. RESULTS: In the PDT arm, five out of the seven treated patients (71%) had their initial tumour size decreased following PDT treatment prior to MMS. The average number of stages in the PDT arm was 1.85, compared to 2.5 in the MMS arm. The average number of sections in the PDT arm was 4.2, in comparison to 5.2 in the MMS arm. CONCLUSION: Our pilot study showed a promising but limited role for PDT as an adjunct in MMS in the treatment of selected cases of basal cell carcinomas. Larger trials, preferably multi-centred are required to further examine the role of this combination therapy. PMID- 26157308 TI - Comparison of Local Flaps and Skin Grafts to Repair Cheek Skin Defects. AB - BACKGROUND AND OBJECTIVE: Selecting the appropriate technique for surgical incisions, and reconstruction of facial defects after skin tumour excision has always been one of the surgeon's biggest concerns. The aim of this study is to compare the results between the local flap and skin graft to reconstruct cheek defects after basal cell carcinoma excision. PATIENTS AND METHODS: In this retrospective study, 40 patients with skin defects resulting from skin tumour (Basal cell carcinoma) excision in cheek zones (16 sub-orbital, 18 bucco mandibular and six auricular) were treated using local flap (n = 20) and skin graft (n = 20) from October 2010 to April 2012. All patients were followed up for 12 months, postoperatively. In addition, general assessments including complications, patient satisfaction, tissue co-ordination, skin colour and hospitalisation days were obtained. RESULTS: Five patients had postoperative hyper-pigmentation complication in the skin graft group and none occurred in the local flap (P = 0.046). In the early postoperative period (2 weeks), mean scores in patient satisfaction, tissue co-ordination and skin colour were statistically significant increase in the local flaps (P < 0.001, P < 0.001, P < 0.001, respectively) and in the later postoperative period (12 months) only mean scores in skin colour significantly increased in the local flaps (P < 0.001). The mean postoperative length of hospitalisation days was 1.7 +/- 0.4 days in the local flap group, and 3.63 +/- 1.16 days in the skin graft group (P = 0.001). CONCLUSION: In the local flap group: Patient satisfaction, tissue co-ordination and skin colour were improved after 2 weeks. Also in 12-months follow up visits, skin colour was improved significantly and the hyperpigmentation was reduced. Generally, in this study the local flaps had better results in clinical outcomes and patient satisfaction. However, for each cheek defect the surgeon must choose the appropriate reconstruction strategy to avoid undesirable outcomes. PMID- 26157309 TI - Comparative Study of Diode Laser Versus Neodymium-Yttrium Aluminum: Garnet Laser Versus Intense Pulsed Light for the Treatment of Hirsutism. AB - INTRODUCTION: Lasers are widely used for the treatment of hirsutism. But the choice of the right laser for the right skin type is very important. Before starting with laser therapy, it is important to assess the skin type, the fluence, the pulse duration and the type of laser to be used. AIMS: To compare the efficacy and side effects of Diode laser, Neodymium-yttrium aluminum - garnet (Nd: YAG) laser and intense pulsed light (IPL) on 30 female patients of hirsutism. MATERIALS AND METHODS: Thirty female patients with hirsutism were selected for a randomised controlled study. The patients were divided into three groups of 10 patients each. In group I patients diode laser was used, in group II patients long pulsed Nd: YAG laser was used and in group III, IPL was used. The patients were evaluated and result graded according to a 4-point scale as excellent, >75% reduction; good, 50-75% reduction; fair; 25-50% reduction; and poor, <25% reduction in hair density. RESULTS: It was seen that the percentage of hair reduction after two sessions of treatment was maximum (40%) in the diode laser group, followed by 35% hair reduction in the Nd: Yag laser group and 10% hair reduction in the IPL group. The percentage of hair reduction after four sessions of treatment was maximum (64%) in the diode laser group, followed by 62% hair reduction in the Nd: Yag laser group and 48% hair reduction in the IPL group. The percentage of hair reduction after eight sessions of treatment was maximum (92%) in the diode laser group, followed by 90% hair reduction in the Nd: YAG group and 70% hair reduction in the IPL group. CONCLUSIONS: To conclude for the Indian skin with dark hairs, the diode laser still stands the test of time. But, since the diode laser has a narrow margin of safety, proper pre and post procedure cooling is recommended. Although, the side effects of Nd: YAG laser are less as compared to the diode laser, it is less efficacious as compared to the diode laser. PMID- 26157311 TI - How I Manage Complications in Aesthetic Surgery. PMID- 26157310 TI - Simple Technique for Facial Dimple. AB - BACKGROUND: Subjects seeking aesthetic surgery for facial dimples are increasing in number. Literature on dimple creation surgery are sparse. Various techniques have been used with their own merits and disadvantages. MATERIALS AND METHODS: Facial dimples were created in 23 cases. All the subjects were females. Five cases were bilateral and the rest were unilateral. RESULTS: Minor complications such as swelling and hematoma were observed in four cases. Infection occurred in two cases. Most of the subjects were satisfied with the results. CONCLUSIONS: Suturing technique is safe, reliable and an easily reproducible way to create facial dimple. LEVEL OF EVIDENCE: IV: Case series. PMID- 26157312 TI - Angiomatosis: A Rare Vascular Proliferation of Head and Neck Region. AB - Angiomatosis is a diffuse vascular lesion which clinically mimics hemangioma or vascular malformation. It usually involves multiple tissues and is histopathologically characterised by proliferation of vessels of varying calibre intimately admixed with large amount of adipose tissue. Its surgical removal is very difficult because of its infiltrative nature. Therefore, a precise histopathological diagnosis is of utmost importance. It is usually seen in females in the first two decades and commonly involves lower extremities. Angiomatosis of head and neck region is very rare. Here we present a rare case of angiomatosis of the lower face involving right cheek and lip in a 4-year-old boy clinically diagnosed as hemangioma. Histopathological differential diagnosis of angiomatosis is also discussed. PMID- 26157313 TI - Treatment of Laser Resistant Granuloma Faciale with Intralesional Triamcinolone acetonide and 5-Fluorouracil Combination Therapy. AB - This report describes a sixty year old male with biopsy proven Granuloma Faciale (GF). The patient had been unsuccessfully treated with multiple therapies. A mixture 0.8 ml 5-Fluorouracil (5FU) and 0.2 ml Kenacort-A was trialled initially to treat this patient, followed by a more varied mixture ratio. These were given at intervals ranging from two weeks to two months. The patient received a total of twenty injections over a period of more than three years. An excellent response was noted and the patient is now able to tolerate long treatment free periods of between nine and twelve months. 5FU is a simple injection material and can be considered by clinicians as an option for treatment of GF. PMID- 26157314 TI - Solitary cylindroma of tragus of the ear mimicking a keloid. AB - Cylindromas are very rare primitive sweat gland tumours differentiating towards eccrine or apocrine line. We present a case of cylindroma of tragus of external ear in a 50-year-old female. It was diagnosed clinically as keloid. After excision, histopathological and immunohistochemistry (IHC) studies confirmed diagnosis of solitary cylindroma. PMID- 26157315 TI - Linear Leucoderma Following Intralesional Steroid: A Report of Three Cases. PMID- 26157316 TI - Giant Acrochordon of Labia Majora: An Uncommon Manifestation of a Common Disease. PMID- 26157317 TI - Clinical Pearl: Use of Indian Dinner Plate 'Thali' as a Surgery Tray in Dermatosurgery and Aesthetics. PMID- 26157318 TI - Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment. AB - Patients with advanced esophageal cancer (T3-4, N) have a poor prognosis. Chemoradiation or chemotherapy before esophagectomy with adequate lymphadenectomy is the standard treatment for patients with resectable advanced esophageal carcinoma. However, only patients with major histopathologic response (regression to less than 10% of the primary tumor) after preoperative treatment will have a prognostic benefit of preoperative chemoradiation. Using current therapy regimens about 40% to 50% of the patients show major histopathological response. The remaining cohort does not benefit from this neoadjuvant approach but might benefit from earlier surgical resection. Therefore, it is an aim to develop tools for response prediction before starting the treatment and for early response assessment identifying responders. The current review discusses the different imaging techniques and the most recent studies about molecular markers for early response prediction. The results show that [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) has a good sensitivity but the specificity is not robust enough for routine clinical use. Newer positron emission tomography detector technology, the combination of FDG-PET with computed tomography, additional evaluation criteria and standardization of evaluation may improve the predictive value. There exist a great number of retrospective studies using molecular markers for prediction of response. Until now the clinical use is missing. But the results of first prospective studies are promising. A future perspective may be the combination of imaging technics and special molecular markers for individualized therapy. Another aspect is the response assessment after finishing neoadjuvant treatment protocol. The different clinical methods are discussed. The results show that until now no non-invasive method is valid enough to assess complete histopathological response. PMID- 26157319 TI - Prediction of radiosensitivity in primary central nervous system germ cell tumors using dynamic contrast-enhanced magnetic resonance imaging. AB - OBJECTIVE: To evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for predicting tumor response to radiotherapy in patients with suspected primary central nervous system (CNS) germ cell tumors (GCTs). METHODS: DCE-MRI parameters of 35 patients with suspected primary CNS GCTs were obtained prior to diagnostic radiation, using the Tofts and Kermode model. Radiosensitivity was determined in tumors diagnosed 2 weeks after radiation by observing changes in tumor size and markers as a response to MRI. Taking radiosensitivity as the gold standard, the cut-off value of DCE-MRI parameters was measured by receiver operating characteristic (ROC) curve. Diagnostic accuracy of DCE-MRI parameters for predicting radiosensitivity was evaluated by ROC curve. RESULTS: A significant elevation in transfer constant (K(trans)) and extravascular extracellular space (Ve) (P=0.000), as well as a significant reduction in rate constant (Kep) (P=0.000) was observed in tumors. K(trans), relative K(trans), and relative Kep of the responsive group were significantly higher than non-responsive groups. No significant difference was found in Kep, Ve, and relative Ve between the two groups. Relative K(trans) showed the best diagnostic value in predicting radiosensitivity with a sensitivity of 100%, specificity of 91.7%, positive predictive value (PPV) of 95.8%, and negative predictive value (NPV) of 100%. CONCLUSIONS: Relative K(trans) appeared promising in predicting tumor response to radiation therapy (RT). It is implied that DCE-MRI pre-treatment is a requisite step in diagnostic procedures and a novel and reliable approach to guide clinical choice of RT. PMID- 26157320 TI - Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer. AB - OBJECTIVE: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. METHODS: According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. RESULTS: In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. CONCLUSIONS: Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies. PMID- 26157321 TI - microRNA-218 suppresses the proliferation, invasion and promotes apoptosis of pancreatic cancer cells by targeting HMGB1. AB - OBJECTIVE: To detect the expression profiles of microRNA-218 (miR-218) in human pancreatic cancer tissue (PCT) and cells and their effects on the biological features of human pancreatic cancer cell line PANC-1 and observe the effect of miR-218 on the expression of the target gene high mobility group box 1 (HMGB1), with an attempt to provide new treatment methods and strategies for pancreatic cancer. METHODS: The expressions of miR-218 in PCT and normal pancreas tissue as well as in various pancreatic cancer cell lines including AsPC-1, BxPC-3, and PANC-1 were determined with quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The change of miR-218 expression in PANC-1 cells was detected using qRT-PCT after the transfection of miR-218 mimic for 48 h. Cell Counting Kit-8 (CCK-8) was applied for detecting the effect of miR-218 on the activity of PANC-1 cells. The effects of miR-218 on the proliferation and apoptosis of PANC-1 cells were analyzed using the flow cytometry. The effect of miR-218 on the migration of PANC-1 cells was detected using the Trans-well migration assay. The HMGB1 was found to be a target gene of miR-218 by luciferase reporter assay, and the effect of miR-218 on the expression of HMGB1 protein in cells were determined using Western blotting. RESULTS: As shown by qRT-PCR, the expressions of miR-218 in PCT and in pancreatic cancer cell line significantly decreased when compared with the normal pancreatic tissue (NPT) (P<0.01). Compared with the control group, the miR-218 expression significantly increased in the PANC-1 group after the transfection of miR-218 mimic for 48 h (P<0.01). Growth curve showed that the cell viability significantly dropped after the overexpression of miR-218 in the PANC-1 cells for two days (P<0.05). Flow cytometry showed that the S-phase fraction significantly dropped after the overexpression of miR-218 (P<0.01) and the percentage of apoptotic cells significantly increased (P<0.01). As shown by the Trans-well migration assay, the enhanced miR-218 expression was associated with a significantly lower number of cells that passed through a Transwell chamber (P<0.01). Luciferase reporter assay showed that, compared with the control group, the relative luciferase activity significantly decreased in the miR-218 mimic group (P<0.01). As shown by the Western blotting, compared with the control group, the HMGB1 protein expression significantly decreased in the PANC-1 group after the transfection of miR-218 mimic for 48 h (P<0.01). CONCLUSIONS: The miR-218 expression decreases in human PCT and cell lines. miR-218 can negatively regulate the HMGB1 protein expression and inhibit the proliferation and invasion of pancreatic cancer cells. A treatment strategy by enhancing the miR-218 expression may benefit the patients with pancreatic cancer. PMID- 26157322 TI - Clinicopathological features and survival analysis of gastroenteropancreatic neuroendocrine neoplasms: a retrospective study in a single center of China. AB - OBJECTIVE: To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) in a Chinese population. METHODS: We investigated 154 consecutive patients (88 males, 66 females; median age 56 years, age range 9-86 years) diagnosed with GEP NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved. RESULTS: The pancreas was the most common site of involvement (63/154, 40.9%). Tumor size varied from 0.3 to 16.0 cm (median, 1.2 cm). The patients were followed up for a median period of 22 months (range, 1-157 months). The estimated 3- and 5-year overall survival (OS) rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome. CONCLUSIONS: Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival. PMID- 26157323 TI - microRNA-218 promotes gemcitabine sensitivity in human pancreatic cancer cells by regulating HMGB1 expression. AB - OBJECTIVE: The purpose of this study was to examine the effect of gemcitabine (GEM) on microRNA-218 (miR-218) expression in human pancreatic cancer cells. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to examine the differences in miR-218 expression between the GEM sensitive BxPC-3 pancreatic cancer cells and GEM-resistant PANC-1 cells. The effect of GEM on the expression of miR-218 in PANC-1 cells was also investigated. PANC-1 cells were transfected either with HMGB1 siRNA to knock down the expression of HMGB1 or with the recombinant HMGB1 expression vector (pcDNA3.1 HMGB1) to overexpress HMGB1. The effect of ectopic expression of HMGB1 on the apoptosis of miR-218-transfected and GEM-treated PANC-1 cells was examined by flow cytometric analysis. RESULTS: The miR-218 expression level was lower in GEM resistant PANC-1 cells compared to GEM-sensitive BxPC-3 cells (P<0.05). The percentage of apoptotic PANC-1 cells was significantly increased in the miR-218 mimic + GEM group compared to the mimic ctrl + GEM group and the normal control group (P<0.01). The HMGB1 expression level was markedly decreased in PANC-1 cells transfected with HMGB1 siRNA but was significantly increased in PANC-1 cells transfected with the recombinant HMGB1 expression vector, pcDNA3.1-HMGB1 (P<0.01). The proportion of apoptotic PANC-1 cells was significantly lower in the miR-218 mimic + GEM + pcDNA3.1-HMGB1 group compared to the miR-218 mimic + GEM + HMGB1 siRNA group (P<0.01). CONCLUSIONS: The expression level of miR-218 was downregulated in the GEM-resistant cell line. miR-218 promoted the sensitivity of PANC-1 cells to GEM, which was achieved mainly through regulating the expression of HMGB1 in PANC-1 cells. PMID- 26157324 TI - Comparison of the clinical characteristics and survival between Uyghur patients with hepatitis virus-related and non-B, non-C hepatocellular carcinoma in Xinjiang, China. AB - OBJECTIVE: To compare the clinical characteristics and prognosis between hepatitis virus-related hepatocellular carcinoma (viral HCC) and non-B, non-C HCC (NBC-HCC) among Uyghur patients in Xinjiang province, China. METHODS: Between 01/01/2000 and 31/12/2012, 319 Uyghur HCC patients were treated at the Cancer Centre of The First Affiliated Hospital of Xinjiang Medical University. The data for the patients were obtained from a retrospective review of the patients' medical records. A total of 18 patients were excluded from the study because of incomplete information. The patients were classified into two groups: viral HCC and NBC-HCC. The clinical characteristics and prognostic factors were statistically analysed. RESULTS: For all 301 patients, gender (P=0.000), area of residence (P=0.002), diabetes mellitus (P=0.009), BMI (P=0.000), cirrhosis (P=0.000), tumour stage (P=0.004), Child-Pugh class (P=0.000), the TBIL level (P=0.000), and the alpha-fetoprotein (AFP) level (P=0.000) were significantly different between the NBC-HCC and viral HCC groups. The NBC-HCC patients tended to be diagnosed at advanced stages; however, the NBC-HCC patients exhibited lower Child-Pugh scores than the viral HCC patients. In all patients examined, the 0.5 , 1-, 3- and 5-year overall survival (OS) rates were 35.6%, 20.3%, 12.6% and 4.5%, respectively. No significant difference in OS was observed between the two groups (P=0.124). Cox multivariate analysis revealed that age (RR =1.539, P=0.001), TNM stage (RR =12.708, P=0.000), portal vein tumour thrombus (PVTT) (RR =2.003, P=0.000), Child-Pugh class (RR =1.715, P=0.000), and TACE + radiotherapy/RFA (RR =0.567, P=0.000) were significant independent prognostic factors for HCC patients. CONCLUSIONS: The clinical characteristics differ between Uyghur patients with NBC-HCC and viral HCC. HCC in the Xinjiang region displays specific regional characteristics. Age, TNM stage, PVTT, Child-Pugh class and TACE + radiotherapy/RFA are significant risk factors that influence patient survival. PMID- 26157325 TI - Presentation delay in breast cancer patients and its association with sociodemographic factors in North Pakistan. AB - BACKGROUND: There is strong evidence that delayed diagnosis of breast cancer is associated with poor survival. The objectives were to determine the frequency of breast cancer patients with delayed presentation, the reasons of delay and its association with different socio-demographic variables in our settings. METHODS: We interviewed 315 histologically confirmed breast cancer patients. Delay was defined as more than 3 months from appearance of symptoms to the consultation from doctor. Questions were asked from each patient which could reflect their understanding about the disease and which could be the likely reasons for their delayed presentation. RESULTS: A total of 39.01% (n=123) of patients presented late and out of those, 40.7% wasted time using alternative medicines; 25.2% were not having enough resources; 17.1% presented late due to painless lump; 10.6% felt shyness and 6.5% presented late due to other reasons. Higher age, negative family history, <8 school years of education and low to middle socio-economic status were significantly associated with delayed presentation (P<0.05). Education and socioeconomic status were two independent variables related to the delayed presentation after adjustment for others [odds ratios (OR) of 2.26, 2.29 and 95% confidence intervals (CI) was 1.25-4.10, 1.06-4.94 respectively]. CONCLUSIONS: Significant percentage of women with breast cancer in North Pakistan is experiencing presentation delay due to their misconceptions about the disease. Coordinated efforts with public health department are needed to educate the focused groups and mitigating the barriers identified in the study. Long term impact will be reduced overall burden of the disease in the region. PMID- 26157326 TI - Epidermal growth factor receptor mutation analysis in cytological specimens and responsiveness to gefitinib in advanced non-small cell lung cancer patients. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is the key predictor of EGFR tyrosine kinase inhibitors (TKIs) efficacy in non-small cell lung cancer (NSCLC). We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations. METHODS: A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system (ARMS). We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate (ORR), disease control rate (DCR) and progression free survival (PFS). RESULTS: Of all patients, EGFR mutation rate was 28.6% (60/210) by direct sequencing and 45.2% (95/210) by ARMS (P<0.001) respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR (48.0% vs. 80.9%, P=0.004) and shorter median PFS (7.4 vs. 10.5 months, P=0.009) as compared with that of EGFR mutation positive patients by both detection methods. CONCLUSIONS: Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy. PMID- 26157327 TI - Single nucleotide polymorphisms of MAGE-A3 gene and its clinical implications in Chinese patients with non-small cell lung cancer (NSCLC). AB - BACKGROUND: Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism (SNP) loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors. METHODS: Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR mRNA expression were detected by qRT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors. RESULTS: Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC (0.681)/CT (0.319), CC (0.660)/CG (0.340), CC (0.681)/CA (0.319), AA (0.984)/AT (0.016) and GG (1.000)/GA (0.000), respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi square tests showed the EGFR mRNA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients. CONCLUSIONS: Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR mRNA expression levels and helpful to the selection of patients for epidermal growth factor receptor (EGFR) targeted immunotherapy. PMID- 26157328 TI - Usefulness of human epididymis protein 4 in predicting cytoreductive surgical outcomes for advanced ovarian tubal and peritoneal carcinoma. AB - OBJECTIVE: Human epididymis protein 4 (HE4) is a promising biomarker of epithelial ovarian cancer (EOC). But its role in assessing the primary optimal debulking (OD) of EOC remains unknown. The purpose of this study is to elucidate the ability of preoperative HE4 in predicting the primary cytoreductive outcomes in advanced EOC, tubal or peritoneal carcinoma. METHODS: We reviewed the records of 90 patients with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at the Department of Obstetrics and Gynecology of Peking University People's Hospital between November 2005 and October 2010. Preoperative serum HE4 and CA125 levels were detected with EIA kit. A receiver operating characteristic (ROC) curve was used to determine the most useful HE4 cut-off value. Logistic regression analysis was performed to identify significant preoperative clinical characteristics to predict optimal primary cytoreduction. RESULTS: OD was achieved in 47.7% (43/48) of patients. The median preoperative HE4 level for patients with OD vs. suboptimal debulking was 423 and 820 pmol/L, respectively (P<0.001). The areas under the ROC curve for HE4 and CA125 were 0.716 and 0.599, respectively (P=0.080). The most useful HE4 cut-off value was 473 pmol/L. Suboptimal cytoreduction was obtained in 66.7% (38/57) of cases with HE4 >=473 pmol/L compared with only 27.3% (9/33) of cases with HE4 <473 pmol/L. At this threshold, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing suboptimal debulking were 81%, 56%, 67%, and 73%, respectively. Logistic regression analysis showed that the patients with HE4 >=473 pmol/L were less likely to achieve OD (odds ratio =5.044, P=0.002). CONCLUSIONS: Preoperative serum HE4 may be helpful to predict whether optimal cytoreductive surgery could be obtained or whether extended cytoreduction would be needed by an interdisciplinary team. PMID- 26157329 TI - Frequency of Apical and Laminal /s/ in Normal and Postglossectomy Patients. AB - American English can be produced with two types of /s/: apical or laminal. These productions differ in that the apical gesture requires independent tongue tip elevation, and the laminal does not. Postglossectomy speakers, who have lost a unilateral portion of the tongue body along the outer edge, lose innervation to the tongue tip. We hypothesize that postglossectomy patients, even those with a preserved tongue tip, will be more likely to use laminal tongue shapes because of reduced control of the tongue tip. This study examines /s/ type, palate height, and related parameters in 24 control participants and 13 patients with lateral resections using cine-MRI and dental casts. Results of this dataset show that palate height affects choice of /s/ in control participants, but not in patients. Patients tend to use laminal /s/. PMID- 26157330 TI - RNA-seq Reveals Complicated Transcriptomic Responses to Drought Stress in a Nonmodel Tropic Plant, Bombax ceiba L. AB - High-throughput transcriptome provides an unbiased approach for understanding the genetic basis and gene functions in response to different conditions. Here we sequenced RNA-seq libraries derived from a Bombax ceiba L. system under a controlled experiment. As a known medicinal and ornamental plant, B. ceiba grows mainly in hot-dry monsoon rainforests in Southeast Asia and Australia. Due to the specific growth environment, it has evolved a unique system that enables a physiologic response to drought stress. To date, few studies have characterized the genome-wide features of drought endurance in B. ceiba. In this study, we first attempted to characterize and identify the most differentially expressed genes and associated functional pathways under drought treatment and normal condition. Using RNA-seq technology, we generated the first transcriptome of B. ceiba and identified 59 differentially expressed genes with greater than 1,000 fold changes under two conditions. The set of upregulated genes implicates interplay among various pathways: plants growth, ubiquitin-mediated proteolysis, polysaccharides hydrolyzation, oxidative phosphorylation and photosynthesis, etc. In contrast, genes associated with stem growth, cell division, fruit ripening senescence, disease resistance, and proline synthesis are repressed. Notably, key genes of high RPKM levels in drought are AUX1, JAZ, and psbS, which are known to regulate the growth of plants, the resistance against abiotic stress, and the photosynthesis process. Furthermore, 16,656 microsatellite markers and 3,071 single-nucleotide polymorphisms (SNPs) were predicted by in silico methods. The identification and functional annotation of differentially expressed genes, microsatellites, and SNPs represent a major step forward and would serve as a valuable resource for understanding the complexity underlying drought endurance and adaptation in B. ceiba. PMID- 26157331 TI - Time-Frequency Analysis of Peptide Microarray Data: Application to Brain Cancer Immunosignatures. AB - One of the gravest dangers facing cancer patients is an extended symptom-free lull between tumor initiation and the first diagnosis. Detection of tumors is critical for effective intervention. Using the body's immune system to detect and amplify tumor-specific signals may enable detection of cancer using an inexpensive immunoassay. Immunosignatures are one such assay: they provide a map of antibody interactions with random-sequence peptides. They enable detection of disease-specific patterns using classic train/test methods. However, to date, very little effort has gone into extracting information from the sequence of peptides that interact with disease-specific antibodies. Because it is difficult to represent all possible antigen peptides in a microarray format, we chose to synthesize only 330,000 peptides on a single immunosignature microarray. The 330,000 random-sequence peptides on the microarray represent 83% of all tetramers and 27% of all pentamers, creating an unbiased but substantial gap in the coverage of total sequence space. We therefore chose to examine many relatively short motifs from these random-sequence peptides. Time-variant analysis of recurrent subsequences provided a means to dissect amino acid sequences from the peptides while simultaneously retaining the antibody-peptide binding intensities. We first used a simple experiment in which monoclonal antibodies with known linear epitopes were exposed to these random-sequence peptides, and their binding intensities were used to create our algorithm. We then demonstrated the performance of the proposed algorithm by examining immunosignatures from patients with Glioblastoma multiformae (GBM), an aggressive form of brain cancer. Eight different frameshift targets were identified from the random-sequence peptides using this technique. If immune-reactive antigens can be identified using a relatively simple immune assay, it might enable a diagnostic test with sufficient sensitivity to detect tumors in a clinically useful way. PMID- 26157332 TI - High-Throughput Sequencing of miRNAs Reveals a Tissue Signature in Gastric Cancer and Suggests Novel Potential Biomarkers. AB - Gastric cancer has a high incidence and mortality rate worldwide; however, the use of biomarkers for its clinical diagnosis remains limited. The microRNAs (miRNAs) are biomarkers with the potential to identify the risk and prognosis as well as therapeutic targets. We performed the ultradeep miRnomes sequencing of gastric adenocarcinoma and gastric antrum without tumor samples. We observed that a small set of those samples were responsible for approximately 80% of the total miRNAs expression, which might represent a miRNA tissue signature. Additionally, we identified seven miRNAs exhibiting significant differences, and, of these, hsa miR-135b and hsa-miR-29c were able to discriminate antrum without tumor from gastric cancer regardless of the histological type. These findings were validated by quantitative real-time polymerase chain reaction. The results revealed that hsa-miR-135b and hsa-miR-29c are potential gastric adenocarcinoma occurrence biomarkers with the ability to identify individuals at a higher risk of developing this cancer, and could even be used as therapeutic targets to allow individualized clinical management. PMID- 26157333 TI - Protective Effect of Piper aduncum Capsule on DMBA-induced Breast Cancer in Rats. AB - The possible protective effect of Piper aduncum capsule on DMBA (dimethylbenz[alpha]anthracene)-induced breast cancer in rats was assessed by monitoring the tumor and lung metastases incidence and recording hematological and biochemical parameters and frequency of micronuclei. Mammary carcinogenesis was induced in 36 female Holtzman rats by providing a single subcutaneous injection of DMBA. Oral administration of P. aduncum capsule lowered adenocarcinoma and lymph node metastases incidence. Pulmonary metastasis was significantly lowered (P < 0.05). Hematological indicators showed that the triglyceride level was significantly lowered (P < 0.01) and high-density lipoprotein (HDL) level was significantly increased (P < 0.01). Also, P. aduncum capsule significantly lowered the C reactive protein (CRP) level (P < 0.01) and malondialdehyde level (P < 0.05). There was a significant decrease in the frequency of DMBA-induced micronucleated polychromatic erythrocyte (P < 0.01). Considering the antitumorigenic, hypolipidemic, anti-inflammatory, antioxidant, and antigenotoxic properties of P. aduncum capsule, we conclude that it has a protective effect on DMBA-induced breast cancer in rats. PMID- 26157334 TI - Molecular Characterization of Pathogenic Acanthamoeba Isolated from Drinking and Recreational water in East Azerbaijan, Northwest Iran. AB - Acanthamoeba- related infections, such as amoebic keratitis and granulomatous amoebic encephalitis, can develop in high-risk population through contaminated water sources. Thus, surveying water resources, particularly those available for human use, is of the utmost importance. In the present study, 67 water samples were collected from water resources in East Azerbaijan, a province in northwestern Iran. Samples were cultured on enriched non-nutrient agar plates, and sequencing-based approaches were used for genotyping. The pathogenic potential of the isolates was determined using thermo- and osmo-tolerance tests. Acanthamoeba were detected in 17 (25.4%) of the 67 collected samples. Sequencing analysis revealed that the isolates belonged to the T3 (23.52%), mixed T3/T4 (5.88%), T4 (58.82%), T5 (5.88%), and T13 (5.88%) genotypes. Through thermo- and osmo-tolerance tests, 88.23% of isolates were resistant to 37 degrees C, 40 degrees C temperature, and 0.5 M and 1 M osmolarity; thus, these isolates had the potential for pathogenicity. These findings point toa serious public health concern in the studied region. This study is the first to report Acanthamoeba isolated from drinking and recreational water sources in East Azerbaijan and Acanthamoeba T13 isolated from tap water in Iran. PMID- 26157335 TI - Using Caffeine as a Water Quality Indicator in the Ambient Monitoring Program for Third Fork Creek Watershed, Durham, North Carolina. AB - Caffeine has been suggested as a chemical indicator for domestic wastewater in freshwater systems, although it is not included in water quality monitoring programs. The Third Fork Creek watershed in Durham, NC, is highly urbanized, with a history of receiving untreated wastewater from leaking and overflowing sanitary sewers. The poor water quality originating in the Third Fork Creek watershed threatens its intended uses and jeopardizes drinking water, aquatic life, and recreational activities provided by Jordan Lake. Organic waste contaminants have been detected in both Third Fork Creek watershed and Jordan Lake; however, the sampling periods were temporary, resulting in a few samples collected during nonstorm periods. It is recommended that (1) the concentration of caffeine and other organic waste contaminants are determined during storm and nonstorm periods and (2) caffeine is monitored regularly with traditional water quality indicators to evaluate the health of Third Fork Creek watershed. PMID- 26157336 TI - Elevated Expression of the Testis-specific Gene WBP2NL in Breast Cancer. AB - Breast cancer is one of the most common causes of cancer death in women; therefore, the study of molecular aspects of breast cancer for finding new biomarkers is important. Recent studies have shown that WW domain-binding protein 2 (WBP2) is important for the oncogenic property of breast cancer. WWP2 N terminal-like (WBP2NL) is a testis-specific signaling protein that induces meiotic resumption and oocyte activation events. Our previous study revealed that WBP2NL gene expression is elevated in actively dividing cells and it might be associated with cellular proliferation and tumorigenic process. However, the clinical relevance and importance of WBP2NL gene in cancer has not been understood yet. Therefore, we were interested in analyzing the expression of WBP2NL gene in human breast cancer tissues and breast cancer cell lines, for the first time. We used reverse transcription-polymerase chain reaction (RT-PCR) and semi-nested RT-PCR to evaluate the expression of WBP2NL in malignant breast cancer and adjacent noncancerous tissue (ANCT) samples, as well as MCF-7 and MDA MB-231 cell lines. The WBP2NL gene was expressed in 45 out of 50 (90%) breast cancer tissues and overexpressed in the MDA-MB-231 cell line. We suggest that WBP2NL may play roles in breast cancer activation maybe through binding to a group I WW domain protein. The elevated expression of WBP2NL gene in breast cancer and MDA-MB-231 cell line leads us to suggest that WBP2NL might be considered as a novel prognostic factor for early diagnosis of breast cancer. PMID- 26157337 TI - What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases. AB - High-intensity interval exercise (HIIE) has gained popularity in recent years for patients with cardiovascular and metabolic diseases. Despite potential benefits, concerns remain about the safety of the acute response (during and/or within 24 hours postexercise) to a single session of HIIE for these cohorts. Therefore, the aim of this study was to perform a systematic review to evaluate the safety of acute HIIE for people with cardiometabolic diseases. Electronic databases were searched for studies published prior to January 2015, which reported the acute responses of patients with cardiometabolic diseases to HIIE (>=80% peak power output or >=85% peak aerobic power, VO2peak). Eleven studies met the inclusion criteria (n = 156; clinically stable, aged 27-66 years), with 13 adverse responses reported (~8% of individuals). The rate of adverse responses is somewhat higher compared to the previously reported risk during moderate intensity exercise. Caution must be taken when prescribing HIIE to patients with cardiometabolic disease. Patients who wish to perform HIIE should be clinically stable, have had recent exposure to at least regular moderate-intensity exercise, and have appropriate supervision and monitoring during and after the exercise session. PMID- 26157338 TI - Renal Denervation in Heart Failure: A New Therapeutic Paradigm. AB - Heart failure constitutes a significant source of morbidity and mortality in the United States, and its incidence and prevalence continue to grow, increasing its burden on the health care system. Renal dysfunction in patients with heart failure is common and has been associated with adverse clinical outcomes. This complex interaction is characterized by a pathophysiological disequilibrium between the heart and the kidney, in which cardiac malfunction promotes renal impairment, which in turn feeds back, resulting in further deterioration of cardiovascular function. Multiple neurohumoral and hemodynamic mechanisms are involved in this cardiorenal dyshomeostasis, including resistance to compensatory cardiac natriuretic peptides, leading to sodium retention, volume overload, and organ remodeling. Previous studies in animal models of heart failure have demonstrated that renal denervation promotes a robust natriuresis and diuresis as well as increased response of endogenous and exogenous natriuretic agents. With the recent development of minimally invasive renal denervation in humans, it is possible to suggest that this technique may become effective and important in the management of renal sodium and water metabolism in heart failure. PMID- 26157339 TI - Revascularization in Severe Left Ventricular Dysfunction: Does Myocardial Viability Even Matter? AB - Left ventricular dysfunction is a powerful prognostic predictor in patients with coronary artery disease and increasing number of patients with CAD and ischemic left ventricular (LV) dysfunction is a major clinical problem. Congestive heart failure is a frequent complication which is associated with significant health care costs and two-third of cases have ischemic cardiomyopathy. In such patients, coronary revascularization can lead to symptomatic and prognostic improvement and reversal of LV remodeling which led to the concept of viable myocardium to select patients in whom recovery of LV function and improvement of prognosis will outweigh the risk of surgical revascularization. The aim of this review article is to understand the different modalities for assessing myocardial viability and clinical impact of revascularization in relation to the evidence of viability in patients with LV dysfunction. PMID- 26157340 TI - Non-Hodgkin Lymphoma of the Stomach in a Patient Treated with Natalizumab. AB - A 61-year-old man with relapsing-remitting multiple sclerosis developed extranodal large B-cell lymphoma of the stomach following monthly natalizumab infusions for 6 years. Development of lymphoproliferative disorders increases with chronic use of immunosuppression. Cases of primary central nervous system lymphoma as well as one case of peripheral T-cell lymphoma have previously been reported with natalizumab use. Given the absence of a known association between multiple sclerosis and extranodal presentations of diffuse large B-cell lymphoma, a causal association with natalizumab administration cannot be excluded. PMID- 26157341 TI - Silver nanoparticle exposure induced mitochondrial stress, caspase-3 activation and cell death: amelioration by sodium selenite. AB - Silver nanoparticles (AgNP), one of the most commonly used engineered nanomaterial for biomedical and industrial applications, has shown a toxic potential to our ecosystems and humans. In this study, murine hippocampal neuronal HT22 cells were used to delineate subcellular responses and mechanisms to AgNP by assessing the response levels of caspase-3, mitochondrial oxygen consumption, reactive oxygen species (ROS), and mitochondrial membrane potential in addition to cell viability testing. Selenium, an essential trace element that has been known to carry protecting property from heavy metals, was tested for its ameliorating potential in the cells exposed to AgNP. Results showed that AgNP reduced cell viability. The toxicity was associated with mitochondrial membrane depolarization, increased accumulation of ROS, elevated mitochondrial oxygen consumption, and caspase-3 activation. Treatment with sodium selenite reduced cell death, stabilized mitochondrial membrane potential and oxygen consumption rate, and prevented accumulation of ROS and activation of caspase-3. It is concluded that AgNP induces mitochondrial stress and treatment with selenite is capable of preventing the adverse effects of AgNP on the mitochondria. PMID- 26157342 TI - Regulation of beta-adrenergic receptor trafficking and lung microvascular endothelial cell permeability by Rab5 GTPase. AB - Rab5 GTPase modulates the trafficking of the cell surface receptors, including G protein-coupled beta-adrenergic receptors (beta-ARs). Here, we have determined the role of Rab5 in regulating the internalization of beta-ARs in lung microvascular endothelial cells (LMECs) and in maintaining the integrity and permeability of endothelial cell barrier. Our data demonstrate that lipopolysaccharide (LPS) treatment disrupts LMEC barrier function and reduces the cell surface expression of beta-ARs. Furthermore, the activation of beta-ARs, particularly beta2-AR, is able to protect the LMEC permeability from LPS injury. Moreover, siRNA-mediated knockdown of Rab5 inhibits both the basal and agonist provoked internalization of beta-ARs, therefore, enhancing the cell surface expression of the receptors and receptor-mediated ERK1/2 activation. Importantly, knockdown of Rab5 not only inhibits the LPS-induced effects on beta-ARs but also protects the LMEC monolayer permeability. All together, these data provide strong evidence indicating a crucial role of Rab5-mediated internalization of beta-ARs in functional regulation of LMECs. PMID- 26157343 TI - Magnolia bioactive constituent 4-O-methylhonokiol prevents the impairment of cardiac insulin signaling and the cardiac pathogenesis in high-fat diet-induced obese mice. AB - In obesity, cardiac insulin resistance is a putative cause of cardiac hypertrophy and dysfunction. In our previous study, we observed that Magnolia extract BL153 attenuated high-fat-diet (HFD)-induced cardiac pathogenic changes. In this study, we further investigated the protective effects of the BL153 bioactive constituent, 4-O-methylhonokiol (MH), against HFD-induced cardiac pathogenesis and its possible mechanisms. C57BL/6J mice were fed a normal diet or a HFD with gavage administration of vehicle, BL153, or MH (low or high dose) daily for 24 weeks. Treatment with MH attenuated HFD-induced obesity, as evidenced by body weight gain, and cardiac pathogenesis, as assessed by the heart weight and echocardiography. Mechanistically, MH treatment significantly reduced HFD-induced impairment of cardiac insulin signaling by preferentially augmenting Akt2 signaling. MH also inhibited cardiac expression of the inflammatory factors tumor necrosis factor-alpha and plasminogen activator inhibitor-1 and increased the phosphorylation of nuclear factor erythroid-derived 2-like 2 (Nrf2) as well as the expression of a Nrf2 downstream target gene heme oxygenase-1. The increased Nrf2 signaling was associated with decreased oxidative stress and damage, as reflected by lowered malondialdehyde and 3-nitrotyrosine levels. Furthermore, MH reduced HFD-induced cardiac lipid accumulation along with lowering expression of cardiac fatty acid translocase/CD36 protein. These results suggest that MH, a bioactive constituent of Magnolia, prevents HFD-induced cardiac pathogenesis by attenuating the impairment of cardiac insulin signaling, perhaps via activation of Nrf2 and Akt2 signaling to attenuate CD36-mediated lipid accumulation and lipotoxicity. PMID- 26157344 TI - Mild ischemic injury leads to long-term alterations in the kidney: amelioration by spironolactone administration. AB - Administration of the mineralocorticoid receptor antagonist spironolactone prevents the development of chronic kidney disease (CKD) after a severe ischemic injury. However, whether brief periods of ischemia lead to CKD and whether spironolactone administration after ischemia may be a useful therapeutic strategy to prevent the gradual deterioration of structure and function remains unexplored. Nineteen male Wistar rats were divided into four groups: rats that underwent renal bilateral ischemia for 10, 20, or 45 min were compared with sham operated rats. Additionally, thirteen male Wistar rats that underwent renal bilateral ischemia for 20 min were divided into an untreated ischemic group (I) and two groups receiving spironolactone, 20 mg/kg by gavage, at either 0 (Sp0) or 1.5-h after ischemia (Sp1.5). The rats were followed up and studied after 9 months. Mild (20 min) and severe (45 min) ischemia induced a progressive increase in proteinuria at varying magnitudes, whereas minor ischemia (10 min) did not modify proteinuria. CKD induced by moderate ischemia was characterized by renal hypertrophy and tubulointerstitial fibrosis. These effects were associated with activation of the transforming growth factor beta (TGFbeta) signaling pathway and up-regulation of endothelin receptor A (ETA) and alpha smooth muscle actin (alphaSMA). Spironolactone treatment immediately or 1.5-h after the ischemic insult prevented the onset of these disorders. Our results show that moderate ischemic insult leads to long-term structural and molecular changes that may compromise renal function in later stages. Additionally, we demonstrate that spironolactone administration after mild ischemia prevents this detrimental effect. PMID- 26157345 TI - Sleep deprivation induces changes in immunity in Trichinella spiralis-infected rats. AB - Sleep is considered an important predictor of immunity. A lack of sleep may reduce immunity, which increases susceptibility to any type of infection. Moreover, sleep deprivation in humans produces changes in both, the percent of circulating immune cells (T cells and NK cells) and cytokine levels (IL-1, IFNgamma, TNPhi-alphaalpha, IL-6 and IL-17). The aim of our study was to investigate whether sleep deprivation produces deregulation on immune variables during the immune response generated against the helminth parasite Trichinella spiralis. Because sleep deprivation is stressful per se, we designed another experiments to compared stress alone (consisting in movement restriction and single housing) with sleep deprivation, in both control (uninfected) and experimental (infected) rats. Our results demonstrate that the sleep deprivation and stress have a differential effect in mesenteric lymph nodes (MLN) and spleen. In uninfected rats sleep deprivation alone produces an increase in natural killer cells (NK+) and B cells (CD45+), accompanied by a decrease in cytotoxic T cells (CD3+CD8+) in spleen; while, in MLN, produces only an increase in natural killer cells (NK+). Both, SD and stress, produce an increased percentage of total T cells (CD3+) in spleen. In the MLN both are also associated to an increase in cytotoxic T cells (CD3+CD8+) and B cells (CD45+). In the spleens of parasitized rats, cell populations did not change. In spleens of both, sleep-deprived and stressed infected rats, we observed an increase in B cells (CD45+). In infected rats, sleep deprivation alone produced an increase in NK cells (NK+). In mesenteric node cell populations of parasitized rats, we observed a decrease in NK cells and an increase in T helper (CD4+) cells in both SD and stressed rats. Rats that were only subjected to stress showed a decrease in B cells (CD45+). These findings suggest that the immune response generated against infection caused by T. spiralis is affected when the sleep pattern is disrupted. These results support the notion that sleep is a fundamental process for an adequate and strong immune response generated against this parasite. PMID- 26157346 TI - Transmissible gastroenteritis virus (TGEV) infection alters the expression of cellular microRNA species that affect transcription of TGEV gene 7. AB - Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. TGEV infection has emerged as a major cause of severe gastroenteritis and leads to alterations of many cellular processes. Meanwhile, the pathogenic mechanism of TGEV is still unclear. microRNAs (miRNAs) are a novel class of small non-coding RNAs which are involved in the regulation of numerous biological processes such as viral infection and cell apoptosis. Accumulating data show that miRNAs are involved in the process of coronavirus infection such as replication of severe acute respiratory syndrome coronavirus (SARS-CoV). However, the link between miRNAs and TGEV infection is unknown. In this study, we performed microRNA microarray assay and predicted targets of altered miRNAs. The results showed TGEV infection caused the change of miRNAs profile. Then we selected miR-4331 for further analysis and subsequently identified cell division cycle-associated protein 7 (CDCA7) as the target of miR-4331. Moreover, miR-4331 showed the ability to inhibit transcription of TGEV gene 7 (a non-structure gene) via directly targeting CDCA7. In conclusion, differentially expressed miR-4331 that is caused by TGEV infection can suppress transcription of TGEV gene 7 via targeting cellular CDCA7. Our key finding is that TGEV selectively manipulates the expression of some cellular miRNAs to regulate its subgenomic transcription. PMID- 26157347 TI - Sensitization of chemo-resistant human chronic myeloid leukemia stem-like cells to Hsp90 inhibitor by SIRT1 inhibition. AB - Development of effective therapeutic strategies to eliminate cancer stem-like cells (CSCs), which play a major role in drug resistance and disease recurrence, is critical to improve cancer treatment outcomes. The current investigation was undertaken to examine the effectiveness of the combination treatment of Hsp90 inhibitor and SIRT1 inhibitor in inhibiting the growth of chemo-resistant stem like cells isolated from human chronic myeloid leukemia K562 cells. Inhibition of SIRT1 by use of SIRT1 siRNA or SIRT1 inhibitors (amurensin G and EX527) effectively potentiated sensitivity of Hsp90 inhibitors (17-AAG and AUY922) in CD44(high) K562 stem-like cells expressing high levels of CSC-related molecules including Oct4, CD34, beta-catenin, c-Myc, mutant p53 (mut p53), BCRP and P glycoprotein (P-gp) as well as CD44. SIRT1 depletion caused significant down regulation of heat shock factor 1 (HSF1)/heat shock proteins (Hsps) as well as these CSC-related molecules, which led to the sensitization of CD44(high) K562 cells to Hsp90 inhibitor by SIRT1 inhibitor. Moreover, 17-AAG-mediated activation of HSF1/Hsps and P-gp-mediated efflux, major causes of Hsp90 inhibitor resistance, was suppressed by SIRT1 inhibitor in K562-CD44(high) cells. Our data suggest that combined treatment with Hsp90 inhibitor and SIRT1 inhibitor could be an effective therapeutic approach to target CSCs that are resistant to current therapies. PMID- 26157348 TI - Yes-associated protein (Yap) is necessary for ciliogenesis and morphogenesis during pronephros development in zebrafish (Danio Rerio). AB - The Hippo signaling pathway and its transcriptional co-activator Yap are known as essential regulators for cell proliferation and organ size. However, little is known about their roles in kidney development and ciliogenesis. We examined expression of Yap during zebrafish embryogenesis, and its transcripts were detected in pronephric duct, while Yap protein was found to be localized in the cytoplasm and apical membrane in kidney epithelium cells. By morpholino (MO) knockdown of yap expression in zebrafish, the injected larve exhibits pronephic cysts and many aspects of ciliopathy, which can be rescued by full-length yap mRNA, but not yap (S127A) mRNA. With transgenic Tg(Na(+)/K(+) ATPase:EGFP), we found that lacking Yap led to expansion and discontinuities of pronephric duct, as well as disorganization of cloaca during pronephros morphogenesis. Mis-located Na(+)/K(+) ATPase and ciliary abnormalities are also detected in pronephric duct of yap morphants. In addition, genetic analysis suggests that yap interacts with ift20, ift88 and arl13b in pronephric cyst formation. Taken together, our data reveals that Yap is required for pronephric duct integrity, maintenance of baso lateral cell polarity, and ciliogenesis during zebrafish kidney development. PMID- 26157349 TI - Overexpression of FGF9 in prostate epithelial cells augments reactive stroma formation and promotes prostate cancer progression. AB - Bone metastasis is the major cause of morbidity and mortality of prostate cancer (PCa). Fibroblast growth factor 9 (FGF9) has been reported to promote PCa bone metastasis. However, the mechanism by which overexpression of FGF9 promotes PCa progression and metastasis is still unknown. Herein, we report that transgenic mice forced to express FGF9 in prostate epithelial cells (F9TG) developed high grade prostatic intraepithelial neoplasia (PIN) in an expression level- and time dependent manner. Moreover, FGF9/TRAMP bigenic mice (F9TRAMP) grew advanced PCa earlier and had higher frequencies of metastasis than TRAMP littermates. We observed tumor microenvironmental changes including hypercellularity and hyperproliferation in the stromal compartment of F9TG and F9TRAMP mice. Expression of TGFbeta1, a key signaling molecule overexpressed in reactive stroma, was increased in F9TG and F9TRAMP prostates. Both in vivo and in vitro data indicated that FGF9 promoted TGFbeta1 expression via increasing cJun mediated signaling. Moreover, in silico analyses showed that the expression level of FGF9 was positively associated with expression of TGFbeta1 and its downstream signaling molecules in human prostate cancers. Collectively, our data demonstrated that overexpressing FGF9 in PCa cells augmented the formation of reactive stroma and promoted PCa initiation and progression. PMID- 26157350 TI - Exosomal transfer of vasorin expressed in hepatocellular carcinoma cells promotes migration of human umbilical vein endothelial cells. AB - Vasorin (VASN) is a type I transmembrane protein that plays important roles in tumor development and vasculogenesis. In this paper, we showed that VASN could be a key mediator of communication between tumor cells and endothelial cells. We confirmed for the first time that HepG2-derived VASN can be transferred to human umbilical vein endothelial cells (HUVECs) via receptor mediated endocytosis of exosomes, at least in part through HSPGs. The HepG2-derived VASN containing exosomes promote migration of recipient HUVECs cells. Our results identify a novel pathway by which a functional protein expressed in tumor cells affects the biological fate of endothelial cells via exosomes. PMID- 26157351 TI - The saponin DT-13 attenuates tumor necrosis factor-alpha-induced vascular inflammation associated with Src/NF-kB/MAPK pathway modulation. AB - This study aimed to explore the effect of DT-13 (25(R,S)-ruscogenin- 1-O- [beta-d glucopyranosyl- (1->2)][beta-d-xylopyranosyl-(1->3)]-beta -d- fucopyranoside) on tumor necrosis factor (TNF)-alpha-induced vascular inflammation and the potential molecular mechanisms. In vitro, DT-13 suppressed TNF-alpha-induced adhesion and migration of human umbilical vein endothelial cells (HUVECs) by inhibiting the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). DT-13 markedly suppressed NF-kB p65 phosphorylation, and when NF-kB p65 was over-expressed, the inhibitory effect of DT-13 on adhesion molecular decreased. DT-13 also suppressed TNF-alpha induced luciferase activities of ICAM-1 and VCAM-1 promoter containing NF-kappaB binding sites. Furthermore, DT-13 markedly suppressed p38 phosphorylation and Src degradation induced by TNF-alpha, whereas had no significant effect on ERK and JNK activation. In vivo, DT-13 at 4 mg/kg prevented vascular inflammation and the expression of adhesion molecules induced by TNF-alpha in mice. These findings suggest that DT-13 abrogates vascular inflammation by down-regulating adhesion molecules associated with modulating the NF-kB, p38MAPK, Src signaling pathways, and NF-kappaB binding site is at least one of the targets of DT-13. This study provides novel information regarding the mechanism by which DT-13 exerts its effects on vascular inflammation, which is important for the onset and progression of various diseases. PMID- 26157352 TI - Significance of antioxidant potential of plants and its relevance to therapeutic applications. AB - Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants. PMID- 26157353 TI - The use of dried blood spot sampling for the measurement of HbA1c: a cross sectional study. AB - BACKGROUND: The use of dried blood spot (DBS) sampling is an alternative to traditional venous blood collection, and particularly useful for people living in rural and remote areas, and for those who are infirm, house-bound or time-poor. The objective of this study was to assess whether the measurement of glycated haemoglobin A1c (HbA1c) in DBS samples provided comparative and acceptably precise results. METHODS: Venous and capillary blood samples were collected from 115 adult participants. After proper instruction, each participant punctured his/her own finger and collected capillary blood samples on pieces of a proprietary cellulose filter paper. Each filter paper was subsequently placed inside a breathable envelope, stored at room temperature, and processed on the same day (D0), four (D4), seven (D7) and fourteen (D14) days after collection. HbA1c was measured in duplicates/triplicates in whole venous blood (WB), capillary blood (capDBS) and venous blood placed on the matrix paper (venDBS), by turbidimetric inhibition immunoassay. Intra-assay coefficients of variation (CV) were calculated. DBS values were compared to WB results using linear regression, Bland-Altman plots and cross-validation models. RESULTS: Eleven and 56 patients had type 1 and type 2 diabetes mellitus, respectively. Mean HbA1c levels were 6.22 +/- 1.11 % for WB samples (n = 115). The median intra-assay CV was lower than 3 % for WB and capDBS on all days. Results from capDBS and venDBS showed high correlation and agreement to WB results, with narrow 95 % limits of agreement (except for results from D14 samples), as observed in Bland-Altman plots. When capDBS values were applied to equations derived from regression analyses, results approached those of WB values. A cross-validation model showed that capDBS results on D0, D4 and D7 were close to the WB results, with prediction intervals that were narrow enough to be clinically acceptable. CONCLUSIONS: The measurement of HbA1c from DBS samples provided results that were comparable to results from WB samples, if measured up to seven days after collection. Intra-assay coefficients of variation were low, results were in agreement with the gold-standard, and prediction intervals were clinically acceptable. The measurement of HbA1c through DBS sampling may be considered in situations where traditional venipuncture is not available. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ID ACTRN12613000769785. PMID- 26157355 TI - Glycomic profiling of carcinoembryonic antigen isolated from human tumor tissue. AB - BACKGROUND: Carcinoembryonic antigen (CEA) is a protein commonly found in human serum, with elevated CEA levels being linked to the progression of a wide range of tumors. It is currently used as a biomarker for malign tumors such as lung cancer and colorectal cancer [Urol Oncol: Semin Orig Invest 352: 644-648, 2013 and Lung Cancer 80: 45-49, 2013]. However, due to its low specificity in clinical applications, CEA can be used for monitoring only, rather than tumor diagnosis. The function of many glycoproteins is critically dependent on their glycosylation pattern, which in turn has the potential to serve in tumor detection. However, little is known about the detailed glycan patterns of CEA. METHODS: To determine these patterns, we isolated and purified CEA proteins from human tumor tissues using immunoaffinity chromatography. The glycan patterns of CEA were then analyzed using a Matrix-Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry(3) (MALDI-TOF-MS(3)) approach. RESULTS: We identified 61 glycoforms in tumor tissue, where CEA is upregulated. These glycosylation entities were identified as bi-antennary, tri-antennary and tetra-antennary structures carrying sialic acid and fucose residues, and include a multitude of glycans previously not reported for CEA. CONCLUSION: Our findings should facilitate a more precise tumor prediction than currently possible, ultimately resulting in improved tumor diagnosis and treatment. PMID- 26157354 TI - Photoperiodic Regulation of Florigen Function in Arabidopsis thaliana. AB - One mechanism through which flowering in response to seasonal change is brought about is by sensing the fluctuation in day-length; the photoperiod. Flowering induction occurs through the production of the florigenic protein FLOWERING LOCUS T (FT) and its movement from the phloem companion cells in the leaf vasculature into the shoot apex, where meristematic reprogramming occurs. FT activation in response to photoperiod condition is accomplished largely through the activity of the transcription factor CONSTANS (CO). Regulation of CO expression and protein stability, as well as the timing of other components via the circadian clock, is a critical mechanism by which plants are able to respond to photoperiod to initiate the floral transition. Modulation of FT expression in response to external and internal stimuli via components of the flowering network is crucial to mediate a fluid flowering response to a variety of environmental parameters. In addition, the regulated movement of FT protein from the phloem to the shoot apex, and interactions that determine floral meristem cell fate, constitute novel mechanisms through which photoperiodic information is translated into flowering time. PMID- 26157356 TI - TRICK or TRP? What Trpc2(-/-) mice tell us about vomeronasal organ mediated innate behaviors. AB - The vomeronasal organ (VNO) plays an important role in mediating semiochemical communications and social behaviors in terrestrial species. Genetic knockout of individual components in the signaling pathways has been used to probe vomeronasal functions, and has provided much insights into how the VNO orchestrates innate behaviors. However, all data do not agree. In particular, knocking out Trpc2, a member of the TRP family of non-selective cationic channel thought to be the main transduction channel in the VNO, results in a number of fascinating behavioral phenotypes that have not been observed in other animals whose vomeronasal function is disrupted. Recent studies have identified signaling pathways that operate in parallel of Trpc2, raising the possibility that Trpc2 mutant animals may display neomorphic behaviors. In this article, I provide a critical analysis of emerging evidence to reconcile the discrepancies and discuss their implications. PMID- 26157357 TI - On the hodological criterion for homology. AB - Owen's pre-evolutionary definition of a homolog as "the same organ in different animals under every variety of form and function" and its redefinition after Darwin as "the same trait in different lineages due to common ancestry" entail the same heuristic problem: how to establish "sameness."Although different criteria for homology often conflict, there is currently a generalized acceptance of gene expression as the best criterion. This gene-centered view of homology results from a reductionist and preformationist concept of living beings. Here, we adopt an alternative organismic-epigenetic viewpoint, and conceive living beings as systems whose identity is given by the dynamic interactions between their components at their multiple levels of composition. We posit that there cannot be an absolute homology criterion, and instead, homology should be inferred from comparisons at the levels and developmental stages where the delimitation of the compared trait lies. In this line, we argue that neural connectivity, i.e., the hodological criterion, should prevail in the determination of homologies between brain supra-cellular structures, such as the vertebrate pallium. PMID- 26157358 TI - Orbitofrontal cortex mediates the differential impact of signaled-reward probability on discrimination accuracy. AB - Orbitofrontal cortex (OFC) function is critical to decision making and behavior based on the value of expected outcomes. While some of the roles the OFC plays in value computations and behavior have been identified, the role of the OFC in modulating cognitive resources based on reward expectancy has not been explored. Here we assessed the involvement of OFC in the interaction between motivation and attention. We tested mice in a sustained-attention task in which explicitly signaling the probability of reward differentially modulates discrimination accuracy. Using pharmacogenetic methods, we generated mice in which neuronal activity in the OFC could be transiently and reversibly inhibited during performance of our signaled-probability task. We found that inhibiting OFC neuronal activity abolished the ability of reward-associated cues to differentially impact accuracy of sustained-attention performance. This failure to modulate attention occurred despite evidence that mice still processed the differential value of the reward-associated cues. These data indicate that OFC function is critical for the ability of a reward-related signal to impact other cognitive and decision-making processes and begin to delineate the neural circuitry involved in the interaction between motivation and attention. PMID- 26157359 TI - Homolog of protein kinase Mzeta maintains context aversive memory and underlying long-term facilitation in terrestrial snail Helix. AB - It has been shown that a variety of long-term memories in different regions of the brain and in different species are quickly erased by local inhibition of protein kinase Mzeta (PKMzeta), a persistently active protein kinase. Using antibodies to mammalian PKMzeta, we describe in the present study the localization of immunoreactive molecules in the nervous system of the terrestrial snail Helix lucorum. Presence of a homolog of PKMzeta was confirmed with transcriptomics. We have demonstrated in behavioral experiments that contextual fear memory disappeared under a blockade of PKMzeta with a selective peptide blocker of PKMzeta zeta inhibitory peptide (ZIP), but not with scrambled ZIP. If ZIP was combined with a "reminder" (20 min in noxious context), no impairment of the long-term contextual memory was observed. In electrophysiological experiments we investigated whether PKMzeta takes part in the maintenance of long-term facilitation (LTF) in the neural circuit mediating tentacle withdrawal. LTF of excitatory synaptic inputs to premotor interneurons was induced by high-frequency nerve stimulation combined with serotonin bath applications and lasted at least 4 h. We found that bath application of 2 * 10(-6) M ZIP at the 90th min after the tetanization reduced the EPSP amplitude to the non-tetanized EPSP values. Applications of the scrambled ZIP peptide at a similar time and concentration didn't affect the EPSP amplitudes. In order to test whether effects of ZIP are specific to the synapses, we performed experiments with LTF of somatic membrane responses to local glutamate applications. It was shown earlier that serotonin application in such an "artificial synapse" condition elicits LTF of responses to glutamate. It was found that ZIP had no effect on LTF in these conditions, which may be explained by the very low concentration of PKMzeta molecules in somata of these identified neurons, as evidenced by immunochemistry. Obtained results suggest that the Helix homolog of PKMzeta might be involved in post-induction maintenance of long-term changes in the nervous system of the terrestrial snail. PMID- 26157360 TI - Sensory transduction at the frog semicircular canal: how hair cell membrane potential controls junctional transmission. AB - At the frog semicircular canals, the afferent fibers display high spontaneous activity (mEPSPs), due to transmitter release from hair cells. mEPSP and spike frequencies are modulated by stimulation that activates the hair cell receptor conductance. The relation between receptor current and transmitter release cannot be studied at the intact semicircular canal. To circumvent the problem, we combined patch-clamp recordings at the isolated hair cell and electrophysiological recordings at the cytoneural junction in the intact preparation. At isolated hair cells, the K channel blocker tetraethylammonium (TEA) is shown to block a fraction of total voltage-dependent K-conductance (IKD) that depends on TEA concentration but not on membrane potential (V m). Considering the bioelectric properties of the hair cell, as previously characterized by this lab, a fixed fractional block of IKD is shown to induce a relatively fixed shift in V m, provided it lies in the range -30 to -10 mV. The same concentrations of TEA were applied to the intact labyrinth while recording from single afferent fibers of the posterior canal, at rest and during mechanical stimulation. At the peak of stimulation, TEA produced increases in mEPSP rate that were linearly related to the shifts produced by the same TEA concentrations (0.1-3 mM) in hair cell V m (0.7-5 mV), with a slope of 29.8 Hz/mV. The membrane potential of the hair cell is not linearly related to receptor conductance, so that the slope of quantal release vs. receptor conductance depends on the prevailing V m (19.8 Hz/nS at -20 mV; 11 Hz/nS at -10 mV). Changes in mEPSP peak size were negligible at rest as well as during stimulation. Since ample spatial summation of mEPSPs occurs at the afferent terminal and threshold-governed spike firing is intrinsically nonlinear, the observed increases in mEPSP frequency, though not very large, may suffice to trigger afferent spike discharge. PMID- 26157361 TI - Hormones and immunity in cancer: are thyroid hormones endocrine players in the microglia/glioma cross-talk? AB - Accumulating evidence indicates that the endocrine and immune systems engage in complex cross-talks in which a prominent role is played by thyroid hormones (THs). The increase of resident vs. monocyte recruited macrophages was shown to be an important effector of the TH 3,3',5'-Triiodo-L-thyronine (T3)-induced protection against inflammation and a key role of T3 in inhibiting the differentiation of peripheral monocytes into macrophages was observed. Herein, we report on the role of T3 as a modulator of microglia, the specialized macrophages of the central nervous system (CNS). Mounting evidence supports a role of microglia and macrophages in the growth and invasion of malignant glioma. In this respect, we unveil the putative involvement of T3 in the microglia/glioma cell communication. Since THs are known to cross the blood-brain barrier, we suggest that T3 not only exerts a direct modulation of brain cancer cell itself but also indirectly promotes glioma growth through a modulation of microglia. Our observations expand available information on the role of TH system in glioma and its microenvironment and highlight the endocrine modulation of microglia as an important target for future therapeutic development of glioma treatments. PMID- 26157363 TI - Editorial: Development of the hypothalamus. PMID- 26157362 TI - Matricellular proteins of the Cyr61/CTGF/NOV (CCN) family and the nervous system. AB - Matricellular proteins are secreted proteins that exist at the border of cells and the extracellular matrix (ECM). However, instead of playing a role in structural integrity of the ECM, these proteins, that act as modulators of various surface receptors, have a regulatory function and instruct a multitude of cellular responses. Among matricellular proteins are members of the Cyr61/CTGF/NOV (CCN) protein family. These proteins exert their activity by binding directly to integrins and heparan sulfate proteoglycans and activating multiple intracellular signaling pathways. CCN proteins also influence the activity of growth factors and cytokines and integrate their activity with integrin signaling. At the cellular level, CCN proteins regulate gene expression and cell survival, proliferation, differentiation, senescence, adhesion, and migration. To date, CCN proteins have been extensively studied in the context of osteo- and chondrogenesis, angiogenesis, and carcinogenesis, but the expression of these proteins is also observed in a variety of tissues. The role of CCN proteins in the nervous system has not been systematically studied or described. Thus, the major aim of this review is to introduce the CCN protein family to the neuroscience community. We first discuss the structure, interactions, and cellular functions of CCN proteins and then provide a detailed review of the available data on the neuronal expression and contribution of CCN proteins to nervous system development, function, and pathology. PMID- 26157364 TI - Commentary: Greater addition of neurons to the olfactory bulb than to the cerebral cortex of eulipotyphlans but not rodents, afrotherians or primates. PMID- 26157365 TI - Contribution of LFP dynamics to single-neuron spiking variability in motor cortex during movement execution. AB - Understanding the sources of variability in single-neuron spiking responses is an important open problem for the theory of neural coding. This variability is thought to result primarily from spontaneous collective dynamics in neuronal networks. Here, we investigate how well collective dynamics reflected in motor cortex local field potentials (LFPs) can account for spiking variability during motor behavior. Neural activity was recorded via microelectrode arrays implanted in ventral and dorsal premotor and primary motor cortices of non-human primates performing naturalistic 3-D reaching and grasping actions. Point process models were used to quantify how well LFP features accounted for spiking variability not explained by the measured 3-D reach and grasp kinematics. LFP features included the instantaneous magnitude, phase and analytic-signal components of narrow band pass filtered (delta,theta,alpha,beta) LFPs, and analytic signal and amplitude envelope features in higher-frequency bands. Multiband LFP features predicted single-neuron spiking (1ms resolution) with substantial accuracy as assessed via ROC analysis. Notably, however, models including both LFP and kinematics features displayed marginal improvement over kinematics-only models. Furthermore, the small predictive information added by LFP features to kinematic models was redundant to information available in fast-timescale (<100 ms) spiking history. Overall, information in multiband LFP features, although predictive of single neuron spiking during movement execution, was redundant to information available in movement parameters and spiking history. Our findings suggest that, during movement execution, collective dynamics reflected in motor cortex LFPs primarily relate to sensorimotor processes directly controlling movement output, adding little explanatory power to variability not accounted by movement parameters. PMID- 26157366 TI - The olivocochlear system and protection from acoustic trauma: a mini literature review. AB - Large intersubject variability in the susceptibility to noise-induced hearing loss (NIHL) is known to occur in both humans and animals. It has been suggested that the olivocochlear system (OCS) plays a significant role in protecting the cochlea from exposure to high levels of noise. A mini literature review about the scientific evidence from animal and human studies about the association between the function of the OCS and susceptibility to NIHL was carried out. Animal data consistently show that de-efferented ears exhibit larger temporary threshold shift (TTS) and permanent threshold shift (PTS) than efferented ears. Data from human studies do not consistently show a correlation between the strength of the OCS function and amount of TTS. Further research on human subjects is required to determine how the OCS function could be used to predict susceptibility to NIHL in individual subjects. PMID- 26157367 TI - Theta oscillation and neuronal activity in rat hippocampus are involved in temporal discrimination of time in seconds. AB - The discovery of time cells revealed that the rodent hippocampus has information regarding time. Previous studies have suggested that the role of hippocampal time cells is to integrate temporally segregated events into a sequence using working memory with time perception. However, it is unclear whether hippocampal cells contribute to time perception itself because most previous studies employed delayed matching-to-sample tasks that did not separately evaluate time perception from working memory processes. Here, we investigated the function of the rat hippocampus in time perception using a temporal discrimination task. In the task, rats had to discriminate between durations of 1 and 3 s to get a reward, and maintaining task-related information as working memory was not required. We found that some hippocampal neurons showed firing rate modulation similar to that of time cells. Moreover, theta oscillation of local field potentials (LFPs) showed a transient enhancement of power during time discrimination periods. However, there were little relationships between the neuronal activities and theta oscillations. These results suggest that both the individual neuronal activities and theta oscillations of LFPs in the hippocampus have a possibility to be engaged in seconds order time perception; however, they participate in different ways. PMID- 26157368 TI - Heterogeneity in perceptual category learning by high functioning children with autism spectrum disorder. AB - Previous research suggests that high functioning (HF) children with autism spectrum disorder (ASD) sometimes have problems learning categories, but often appear to perform normally in categorization tasks. The deficits that individuals with ASD show when learning categories have been attributed to executive dysfunction, general deficits in implicit learning, atypical cognitive strategies, or abnormal perceptual biases and abilities. Several of these psychological explanations for category learning deficits have been associated with neural abnormalities such as cortical underconnectivity. The present study evaluated how well existing neurally based theories account for atypical perceptual category learning shown by HF children with ASD across multiple category learning tasks involving novel, abstract shapes. Consistent with earlier results, children's performances revealed two distinct patterns of learning and generalization associated with ASD: one was indistinguishable from performance in typically developing children; the other revealed dramatic impairments. These two patterns were evident regardless of training regimen or stimulus set. Surprisingly, some children with ASD showed both patterns. Simulations of perceptual category learning could account for the two observed patterns in terms of differences in neural plasticity. However, no current psychological or neural theory adequately explains why a child with ASD might show such large fluctuations in category learning ability across training conditions or stimulus sets. PMID- 26157369 TI - Association of oxytocin level and less severe forms of childhood maltreatment history among healthy Japanese adults involved with child care. AB - BACKGROUND: Oxytocin (OT) is known to play a role in stress regulation. The association between childhood maltreatment history and neuropeptide OT concentration is inconsistent due to the varying degrees of severity of childhood maltreatment, among other contributing factors. Less severe forms of childhood maltreatment history might enhance OT concentrations as a response to coping with social stress within the family. The purpose of this study is to investigate the association between less severe forms of childhood maltreatment history and OT concentrations among healthy adults. METHOD: Eighty adults (49 women and 31 men) with 18- to 48-month-old children were recruited using a snowball sample in Tokyo, Japan. Urine samples were collected for OT measurement. Less severe (low and moderate) childhood maltreatment history, including physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse, was assessed using the self-report questionnaire, the Childhood Trauma Questionnaire. RESULTS: Less severe physical abuse was significantly associated with higher OT concentration after adjusting for age (p = 0.014). Also, less severe forms of physical abuse were independently significantly associated with higher OT concentration after controlling for other types of childhood maltreatment (p = 0.027). A positive dose-response association between the number of less severe childhood maltreatment types and OT concentration was observed (p = 0.031). CONCLUSION: A history of less severe forms of childhood physical abuse was associated with higher OT concentration in healthy adults. Poly-victimization of several types of less severe childhood maltreatment was also associated with higher OT concentrations. Less severe forms of childhood maltreatment might enhance OT concentrations in order to cope with social stress. PMID- 26157370 TI - Lentiviral silencing of GSK-3beta in adult dentate gyrus impairs contextual fear memory and synaptic plasticity. AB - Attempts have been made to use glycogen synthase kinase-3 beta (GSK3beta) inhibitors for prophylactic treatment of neurocognitive conditions. However the use of lithium, a non-specific inhibitor of GSK3beta results in mild cognitive impairment in humans. The effects of global GSK3beta inhibition or knockout on learning and memory in healthy adult mice are also inconclusive. Our study aims to better understand the role of GSK3beta in learning and memory through a more regionally, targeted approach, specifically performing lentiviral-mediated knockdown of GSK3beta within the dentate gyrus (DG). DG-GSK3beta-silenced mice showed impaired contextual fear memory retrieval. However, cue fear memory, spatial memory, locomotor activity and anxiety levels were similar to control. These GSK3beta-silenced mice also showed increased induction and maintenance of DG long-term potentiation (DG-LTP) compared to control animals. Thus, this region specific, targeted knockdown of GSK3beta in the DG provides better understanding on the role of GSK3beta in learning and memory. PMID- 26157371 TI - Individual differences in the influence of task-irrelevant Pavlovian cues on human behavior. AB - Pavlovian-to-instrumental transfer (PIT) refers to the process of a Pavlovian reward-paired cue acquiring incentive motivational proprieties that drive choices. It represents a crucial phenomenon for understanding cue-controlled behavior, and it has both adaptive and maladaptive implications (i.e., drug taking). In animals, individual differences in the degree to which such cues bias performance have been identified in two types of individuals that exhibit distinct Conditioned Responses (CR) during Pavlovian conditioning: Sign-Trackers (ST) and Goal-Trackers (GT). Using an appetitive PIT procedure with a monetary reward, the present study investigated, for the first time, the extent to which such individual differences might affect the influence of reward-paired cues in humans. In a first task, participants learned an instrumental response leading to reward; then, in a second task, a visual Pavlovian cue was associated with the same reward; finally, in a third task, PIT was tested by measuring the preference for the reward-paired instrumental response when the task-irrelevant reward paired cue was presented, in the absence of the reward itself. In ST individuals, but not in GT individuals, reward-related cues biased behavior, resulting in an increased likelihood to perform the instrumental response independently paired with the same reward when presented with the task-irrelevant reward-paired cue, even if the reward itself was no longer available (i.e., stronger PIT effect). This finding has important implications for developing individualized treatment for maladaptive behaviors, such as addiction. PMID- 26157373 TI - Dreaming and Neuroesthetics. AB - This paper, which is limited to the art of painting, aims to support the idea that a substantial insertion of concepts and methods drawn on dream psychology and dream neuroscience can contribute to the advancements of Neuroesthetics. The historical and scientific reasons are discussed that have determined the so far poor role played by the dream phenomenon in the developments of Neuroesthetics. In the light of recent advancements in psychophysiological research, a method of analyzing artistic products is proposed that is based on the recognition of precise features proper of the dreaming experience. Four examples are given for application of this method, regarding works by Giorgione, Leonardo da Vinci, Vermeer, and Millais, respectively. PMID- 26157372 TI - The Neurobiology and Psychology of Pedophilia: Recent Advances and Challenges. AB - A pedophilic disorder is recognized for its impairment to the individual and for the harm it may cause to others. Pedophilia is often considered a side issue and research into the nature of pedophilia is delayed in comparison to research into other psychiatric disorders. However, with the increasing use of neuroimaging techniques, such as functional and structural magnetic resonance imaging (sMRI, fMRI), together with neuropsychological studies, we are increasing our knowledge of predisposing and accompanying factors contributing to pedophilia development. At the same time, we are faced with methodological challenges, such as group differences between studies, including age, intelligence, and comorbidities, together with a lack of careful assessment and control of child sexual abuse. Having this in mind, this review highlights the most important studies investigating pedophilia, with a strong emphasis on (neuro-) biological studies, combined with a brief explanation of research into normal human sexuality. We focus on some of the recent theories on the etiology of pedophilia such as the concept of a general neurodevelopmental disorder and/or alterations of structure and function in frontal, temporal, and limbic brain areas. With this approach, we aim to not only provide an update and overview but also a framework for future research and to address one of the most significant questions of how pedophilia may be explained by neurobiological and developmental alterations. PMID- 26157375 TI - Automatic sleep spindle detection: benchmarking with fine temporal resolution using open science tools. AB - Sleep spindle properties index cognitive faculties such as memory consolidation and diseases such as major depression. For this reason, scoring sleep spindle properties in polysomnographic recordings has become an important activity in both research and clinical settings. The tediousness of this manual task has motivated efforts for its automation. Although some progress has been made, increasing the temporal accuracy of spindle scoring and improving the performance assessment methodology are two aspects needing more attention. In this paper, four open-access automated spindle detectors with fine temporal resolution are proposed and tested against expert scoring of two proprietary and two open-access databases. Results highlight several findings: (1) that expert scoring and polysomnographic databases are important confounders when comparing the performance of spindle detectors tested using different databases or scorings; (2) because spindles are sparse events, specificity estimates are potentially misleading for assessing automated detector performance; (3) reporting the performance of spindle detectors exclusively with sensitivity and specificity estimates, as is often seen in the literature, is insufficient; including sensitivity, precision and a more comprehensive statistic such as Matthew's correlation coefficient, F1-score, or Cohen's kappa is necessary for adequate evaluation; (4) reporting statistics for some reasonable range of decision thresholds provides a much more complete and useful benchmarking; (5) performance differences between tested automated detectors were found to be similar to those between available expert scorings; (6) much more development is needed to effectively compare the performance of spindle detectors developed by different research teams. Finally, this work clarifies a long-standing but only seldomly posed question regarding whether expert scoring truly is a reliable gold standard for sleep spindle assessment. PMID- 26157374 TI - Combinations of stroke neurorehabilitation to facilitate motor recovery: perspectives on Hebbian plasticity and homeostatic metaplasticity. AB - Motor recovery after stroke involves developing new neural connections, acquiring new functions, and compensating for impairments. These processes are related to neural plasticity. Various novel stroke rehabilitation techniques based on basic science and clinical studies of neural plasticity have been developed to aid motor recovery. Current research aims to determine whether using combinations of these techniques can synergistically improve motor recovery. When different stroke neurorehabilitation therapies are combined, the timing of each therapeutic program must be considered to enable optimal neural plasticity. Synchronizing stroke rehabilitation with voluntary neural and/or muscle activity can lead to motor recovery by targeting Hebbian plasticity. This reinforces the neural connections between paretic muscles and the residual motor area. Homeostatic metaplasticity, which stabilizes the activity of neurons and neural circuits, can either augment or reduce the synergic effect depending on the timing of combination therapy and types of neurorehabilitation that are used. Moreover, the possibility that the threshold and degree of induced plasticity can be altered after stroke should be noted. This review focuses on the mechanisms underlying combinations of neurorehabilitation approaches and their future clinical applications. We suggest therapeutic approaches for cortical reorganization and maximal functional gain in patients with stroke, based on the processes of Hebbian plasticity and homeostatic metaplasticity. Few of the possible combinations of stroke neurorehabilitation have been tested experimentally; therefore, further studies are required to determine the appropriate combination for motor recovery. PMID- 26157376 TI - Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States. AB - Alcohol consumption patterns and recognition of health outcomes related to hazardous drinking vary widely internationally, raising the question whether these national differences are reflected in brain damage observed in alcoholism. This retrospective analysis assessed variability of alcoholism's effects on brain cerebrospinal fluid (CSF) and white matter volumes between France and the United States (U.S.). MRI data from two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) were acquired on 1.5T imaging systems in 287 controls, 165 uncomplicated alcoholics (ALC), and 26 alcoholics with Korsakoff's Syndrome (KS). All data were analyzed at the U.S. site using atlas-based parcellation. Results revealed graded CSF volume enlargement from ALC to KS and white matter volume deficits in KS only. In ALC from France but not the U.S., CSF and white matter volumes correlated with lifetime alcohol consumption, alcoholism duration, and length of sobriety. MRI highlighted CSF volume enlargement in both ALC and KS, serving as a basis for an ex vacuo process to explain correlated gray matter shrinkage. By contrast, MRI provided a sensitive in vivo biomarker of white matter volume shrinkage in KS only, suggesting a specific process sensitive to mechanisms contributing to Wernicke's encephalopathy, the precursor of KS. Identified structural brain abnormalities may provide biomarkers underlying alcoholism's heterogeneity in and among nations and suggest a substrate of gray matter tissue shrinkage. Proposed are hypotheses for national differences in interpreting whether the severity of sequelae observe a graded phenomenon or a continuum from uncomplicated alcoholism to alcoholism complicated by KS. PMID- 26157379 TI - The development of prospective memory across adolescence: an event-related potential analysis. AB - Prospective memory (PM) is an important cognitive function vital for day-to-day functioning. Although there has been extensive research into the decline of PM in older adulthood, little is known about its developmental trajectory throughout adolescence, a time of important brain maturation. In the present study, the development of PM was examined in 85 participants across the following groups: 12 to 13-year-olds (n = 19), 14 to 15-year-olds (n = 21), 16 to 17-year-olds (n = 19), and 18 to 19-year-olds (n = 26). A 30-cue (30 min) event-based PM task (with font-color stimuli as PM cues and a lexical-decision task as the ongoing task) was used while recording Event-Related Potentials (ERPs). The well-established neural correlates of PM, the N300 and parietal positivity, were examined across the age groups. In addition, hierarchical multiple regressions were used to examine the unique contribution of executive functioning measures (viz., the Self Ordered Pointing Task [SOPT], the Stroop task, and Trail Making Test [TMT]) on the ERP components of PM (after controlling for age). First, the established components of ERPs associated with prospective remembering (i.e., N300 and parietal positivity) were detected for each age group. Second, although there were no significant age- group differences on the amplitude of the N300, the amplitude of the parietal positivity was found to be different between the 12 to 13-year-olds and 18 to 19-year-olds (viz., the 12 to 13-year-olds had the highest amplitude). Third, for the contribution of executive functioning measures on the amplitude of the ERP components of PM, the regression on the N300 was not significant, however, the SOPT beta weights were significant predictors of the amplitude of the parietal positivity. This relationship was found to be specific for the central and right electrode region. These findings are discussed within the context of brain development and executive functioning along with particular task demands, which may contribute to age-related PM differences across adolescence. Moreover, the findings suggest that cognitive processes associated with parietal positivity may continue to develop across adolescence. PMID- 26157378 TI - Dose-response relationships using brain-computer interface technology impact stroke rehabilitation. AB - Brain-computer interfaces (BCIs) are an emerging novel technology for stroke rehabilitation. Little is known about how dose-response relationships for BCI therapies affect brain and behavior changes. We report preliminary results on stroke patients (n = 16, 11 M) with persistent upper extremity motor impairment who received therapy using a BCI system with functional electrical stimulation of the hand and tongue stimulation. We collected MRI scans and behavioral data using the Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) before, during, and after the therapy period. Using anatomical and functional MRI, we computed Laterality Index (LI) for brain activity in the motor network during impaired hand finger tapping. Changes from baseline LI and behavioral scores were assessed for relationships with dose, intensity, and frequency of BCI therapy. We found that gains in SIS Strength were directly responsive to BCI therapy: therapy dose and intensity correlated positively with increased SIS Strength (p <= 0.05), although no direct relationships were identified with ARAT or 9-HPT scores. We found behavioral measures that were not directly sensitive to differences in BCI therapy administration but were associated with concurrent brain changes correlated with BCI therapy administration parameters: therapy dose and intensity showed significant (p <= 0.05) or trending (0.05 < p < 0.1) negative correlations with LI changes, while therapy frequency did not affect LI. Reductions in LI were then correlated (p <= 0.05) with increased SIS Activities of Daily Living scores and improved 9-HPT performance. Therefore, some behavioral changes may be reflected by brain changes sensitive to differences in BCI therapy administration, while others such as SIS Strength may be directly responsive to BCI therapy administration. Data preliminarily suggest that when using BCI in stroke rehabilitation, therapy frequency may be less important than dose and intensity. PMID- 26157377 TI - Pathophysiology of ADHD and associated problems-starting points for NF interventions? AB - Attention deficit hyperactivity disorder (ADHD) is characterized by severe and age-inappropriate levels of hyperactivity, impulsivity and inattention. ADHD is a heterogeneous disorder, and the majority of patients show comorbid or associated problems from other psychiatric disorders. Also, ADHD is associated with cognitive and motivational problems as well as resting-state abnormalities, associated with impaired brain activity in distinct neuronal networks. This needs to be considered in a multimodal treatment, of which neurofeedback (NF) may be a promising component. During NF, specific brain activity is fed-back using visual or auditory signals, allowing the participants to gain control over these otherwise unaware neuronal processes. NF may be used to directly improve underlying neuronal deficits, and/or to establish more general self-regulatory skills that may be used to compensate behavioral difficulties. The current manuscript describes pathophysiological characteristics of ADHD, heterogeneity of ADHD subtypes and gender differences, as well as frequently associated behavioral problems such as oppositional defiant/conduct or tic disorder. It is discussed how NF may be helpful as a treatment approach within these contexts. PMID- 26157380 TI - "Brain MR spectroscopy in autism spectrum disorder-the GABA excitatory/inhibitory imbalance theory revisited". AB - Magnetic resonance spectroscopy (MRS) from voxels placed in the left anterior cingulate cortex (ACC) was measured from 14 boys with Autism Spectrum Disorder (ASD) and 24 gender and age-matched typically developing (TD) control group. Our main aims were to compare the concentration of gamma-aminobutyric acid (GABA) between the two groups, and to investigate the relationship between brain metabolites and autism symptom severity in the ASD group. We did find a significant negative correlation in the ASD group between Autism Spectrum Screening Questionnaire (ASSQ) and GABA+/Cr, which may imply that severity of symptoms in ASD is associated with differences in the level of GABA in the brain, supporting the excitatory/inhibitory (E/I) imbalance theory. However we did not find a significant difference between the two groups in GABA levels. PMID- 26157381 TI - An exponential filter model predicts lightness illusions. AB - Lightness, or perceived reflectance of a surface, is influenced by surrounding context. This is demonstrated by the Simultaneous Contrast Illusion (SCI), where a gray patch is perceived lighter against a black background and vice versa. Conversely, assimilation is where the lightness of the target patch moves toward that of the bounding areas and can be demonstrated in White's effect. Blakeslee and McCourt (1999) introduced an oriented difference-of-Gaussian (ODOG) model that is able to account for both contrast and assimilation in a number of lightness illusions and that has been subsequently improved using localized normalization techniques. We introduce a model inspired by image statistics that is based on a family of exponential filters, with kernels spanning across multiple sizes and shapes. We include an optional second stage of normalization based on contrast gain control. Our model was tested on a well-known set of lightness illusions that have previously been used to evaluate ODOG and its variants, and model lightness values were compared with typical human data. We investigate whether predictive success depends on filters of a particular size or shape and whether pooling information across filters can improve performance. The best single filter correctly predicted the direction of lightness effects for 21 out of 27 illusions. Combining two filters together increased the best performance to 23, with asymptotic performance at 24 for an arbitrarily large combination of filter outputs. While normalization improved prediction magnitudes, it only slightly improved overall scores in direction predictions. The prediction performance of 24 out of 27 illusions equals that of the best performing ODOG variant, with greater parsimony. Our model shows that V1-style orientation-selectivity is not necessary to account for lightness illusions and that a low-level model based on image statistics is able to account for a wide range of both contrast and assimilation effects. PMID- 26157382 TI - Crossmodal deficit in dyslexic children: practice affects the neural timing of letter-speech sound integration. AB - A failure to build solid letter-speech sound associations may contribute to reading impairments in developmental dyslexia. Whether this reduced neural integration of letters and speech sounds changes over time within individual children and how this relates to behavioral gains in reading skills remains unknown. In this research, we examined changes in event-related potential (ERP) measures of letter-speech sound integration over a 6-month period during which 9 year-old dyslexic readers (n = 17) followed a training in letter-speech sound coupling next to their regular reading curriculum. We presented the Dutch spoken vowels /a/ and /o/ as standard and deviant stimuli in one auditory and two audiovisual oddball conditions. In one audiovisual condition (AV0), the letter "a" was presented simultaneously with the vowels, while in the other (AV200) it was preceding vowel onset for 200 ms. Prior to the training (T1), dyslexic readers showed the expected pattern of typical auditory mismatch responses, together with the absence of letter-speech sound effects in a late negativity (LN) window. After the training (T2), our results showed earlier (and enhanced) crossmodal effects in the LN window. Most interestingly, earlier LN latency at T2 was significantly related to higher behavioral accuracy in letter-speech sound coupling. On a more general level, the timing of the earlier mismatch negativity (MMN) in the simultaneous condition (AV0) measured at T1, significantly related to reading fluency at both T1 and T2 as well as with reading gains. Our findings suggest that the reduced neural integration of letters and speech sounds in dyslexic children may show moderate improvement with reading instruction and training and that behavioral improvements relate especially to individual differences in the timing of this neural integration. PMID- 26157384 TI - Editorial: State-dependent brain computation. PMID- 26157383 TI - Task-concurrent anodal tDCS modulates bilateral plasticity in the human suprahyoid motor cortex. AB - Transcranial direct current stimulation (tDCS) is a non-invasive method to modulate cortical excitability in humans. Here, we examined the effects of anodal tDCS on suprahyoid motor evoked potentials (MEP) when applied over the hemisphere with stronger and weaker suprahyoid/submental projections, respectively, while study participants performed a swallowing task. Thirty healthy volunteers were invited to two experimental sessions and randomly assigned to one of two different groups. While in the first group stimulation was targeted over the hemisphere with stronger suprahyoid projections, the second group received stimulation over the weaker suprahyoid projections. tDCS was applied either as anodal or sham stimulation in a random cross-over design. Suprahyoid MEPs were assessed immediately before intervention, as well as 5, 30, 60, and 90 min after discontinuation of stimulation from both the stimulated and non-stimulated contralateral hemisphere. We found that anodal tDCS (a-tDCS) had long-lasting effects on suprahyoid MEPs on the stimulated side in both groups (tDCS targeting the stronger projections: F (1,14) = 96.2, p < 0.001; tDCS targeting the weaker projections: F (1,14) = 37.45, p < 0.001). While MEPs did not increase when elicited from the non-targeted hemisphere after stimulation of the stronger projections (F (1,14) = 0.69, p = 0.42), we found increased MEPs elicited from the non-targeted hemisphere after stimulating the weaker projections (at time points 30-90 min) (F (1,14) = 18.26, p = 0.001). We conclude that anodal tDCS has differential effects on suprahyoid MEPs elicited from the targeted and non targeted hemisphere depending on the site of stimulation. This finding may be important for the application of a-tDCS in patients with dysphagia, for example after stroke. PMID- 26157385 TI - A reconfigurable visual-programming library for real-time closed-loop cellular electrophysiology. AB - Most of the software platforms for cellular electrophysiology are limited in terms of flexibility, hardware support, ease of use, or re-configuration and adaptation for non-expert users. Moreover, advanced experimental protocols requiring real-time closed-loop operation to investigate excitability, plasticity, dynamics, are largely inaccessible to users without moderate to substantial computer proficiency. Here we present an approach based on MATLAB/Simulink, exploiting the benefits of LEGO-like visual programming and configuration, combined to a small, but easily extendible library of functional software components. We provide and validate several examples, implementing conventional and more sophisticated experimental protocols such as dynamic-clamp or the combined use of intracellular and extracellular methods, involving closed loop real-time control. The functionality of each of these examples is demonstrated with relevant experiments. These can be used as a starting point to create and support a larger variety of electrophysiological tools and methods, hopefully extending the range of default techniques and protocols currently employed in experimental labs across the world. PMID- 26157386 TI - Elderly Use Proprioception Rather than Visual and Vestibular Cues for Postural Motor Control. AB - Multiple factors have been proposed to contribute to the deficits of postural control in the elderly. They were summarized as sensory, motor, and higher-level adaptation deficits. Using a model-based approach, we aimed to identify which of these deficits mainly determine age-related changes in postural control. We analyzed postural control of 20 healthy elderly people with a mean age of 74 years. The findings were compared to data from 19 healthy young volunteers (mean age 28 years) and 16 healthy middle-aged volunteers (mean age 48 years). Postural control was characterized by spontaneous sway measures and measures of perturbed stance. Perturbations were induced by pseudorandom anterior-posterior tilts of the body support surface. We found that spontaneous sway amplitude and velocity were significantly larger, and sway frequencies were higher in elderly compared to young people. Body excursions as a function of tilt stimuli were clearly different in elderly compared to young people. Based on simple feedback model simulations, we found that elderly favor proprioceptive over visual and vestibular cues, other than younger subjects do. Moreover, we identified an increase in overall time delay challenging the feedback systems stability, and a decline in the amplitude of the motor feedback, probably representing weakness of the motor system. In general, these parameter differences between young and old may result from both deficits and compensation strategies in the elderly. Our model-based findings correlate well with deficits measured with clinical balance scores, which are widely used in clinical practice. PMID- 26157387 TI - Role of physical and mental training in brain network configuration. AB - It is hypothesized that the topology of brain networks is constructed by connecting nodes which may be continuously remodeled by appropriate training. Efficiency of physical and/or mental training on the brain relies on the flexibility of networks' architecture molded by local remodeling of proteins and synapses of excitatory neurons producing transformations in network topology. Continuous remodeling of proteins of excitatory neurons is fine-tuning the scaling and strength of excitatory synapses up or down via regulation of intra cellular metabolic and regulatory networks of the genome-transcriptome-proteome interface. Alzheimer's disease is a model of "energy cost-driven small-world network disorder" with dysfunction of high-energy cost wiring as the network global efficiency is impaired by the deposition of an informed agent, the amyloid beta, selectively targeting high-degree nodes. In schizophrenia, the interconnectivity and density of rich-club networks are significantly reduced. Training-induced homeostatic synaptogenesis-enhancement, presumably via reconfiguration of brain networks into greater small-worldness, appears essential in learning, memory, and executive functions. A macroscopic cartography of creation-removal of synaptic connections in a macro-network, and at the intra cellular scale, micro-networks regulate the physiological mechanisms for the preferential attachment of synapses. The strongest molecular relationship of exercise and functional connectivity was identified for brain-derived neurotrophic factor (BDNF). The allele variant, rs7294919, also shows a powerful relationship with the hippocampal volume. How the brain achieves this unique quest of reconfiguration remains a puzzle. What are the underlying mechanisms of synaptogenesis promoting communications brain <-> muscle and brain <-> brain in such trainings? What is the respective role of independent mental, physical, or combined-mental-physical trainings? Physical practice seems to be playing an instrumental role in the cognitive enhancement (brain <-> muscle com.). However, mental training, meditation or virtual reality (films, games) require only minimal motor activity and cardio-respiratory stimulation. Therefore, other potential paths (brain <-> brain com.) molding brain networks are nonetheless essential. Patients with motor neuron disease/injury (e.g., amyotrophic lateral sclerosis, traumatism) also achieve successful cognitive enhancement albeit they may only elicit mental practice. PMID- 26157388 TI - The disengagement of visual attention in Alzheimer's disease: a longitudinal eye tracking study. AB - INTRODUCTION: Eye tracking provides a convenient and promising biological marker of cognitive impairment in patients with neurodegenerative disease. Here we report a longitudinal study of saccadic eye movements in a sample of patients with Alzheimer's disease and elderly control participants who were assessed at the start of the study and followed up 12-months later. METHODS: Eye movements were measured in the standard gap and overlap paradigms, to examine the longitudinal trends in the ability to disengage attention from a visual target. RESULTS: Overall patients with Alzheimer's disease had slower reaction times than the control group. However, after 12-months, both groups showed faster and comparable reductions in reaction times to the gap, compared to the overlap stimulus. Interestingly, there was a general improvement for both groups with more accurately directed saccades and speeding of reaction times after 12-months. CONCLUSIONS: These findings point to the value of longer-term studies and follow up assessment to ascertain the effects of dementia on oculomotor control. PMID- 26157389 TI - Mechanisms for redox-regulation of protein kinase C. AB - Protein kinase C (PKC) is comprised of a family of signal-regulated enzymes that play pleiotropic roles in the control of many physiological and pathological responses. PKC isoforms are traditionally viewed as allosterically activated enzymes that are recruited to membranes by growth factor receptor-generated lipid cofactors. An inherent assumption of this conventional model of PKC isoform activation is that PKCs act exclusively at membrane-delimited substrates and that PKC catalytic activity is an inherent property of each enzyme that is not altered by the activation process. This traditional model of PKC activation does not adequately explain the many well-documented actions of PKC enzymes in mitochondrial, nuclear, and cardiac sarcomeric (non-sarcolemmal) subcellular compartments. Recent studies address this dilemma by identifying stimulus specific differences in the mechanisms for PKC isoform activation during growth factor activation versus oxidative stress. This review discusses a number of non canonical redox-triggered mechanisms that can alter the catalytic properties and subcellular compartmentation patterns of PKC enzymes. While some redox-activated mechanisms act at structural determinants that are common to all PKCs, the redox dependent mechanism for PKCdelta activation requires Src-dependent tyrosine phosphorylation of a unique phosphorylation motif on this enzyme and is isoform specific. Since oxidative stress contributes to pathogenesis of a wide range of clinical disorders, these stimulus-specific differences in the controls and consequences of PKC activation have important implications for the design and evaluation of PKC-targeted therapeutics. PMID- 26157390 TI - Relationships between predicted moonlighting proteins, human diseases, and comorbidities from a network perspective. AB - Moonlighting proteins are a subset of multifunctional proteins characterized by their multiple, independent, and unrelated biological functions. We recently set up a large-scale identification of moonlighting proteins using a protein-protein interaction (PPI) network approach. We established that 3% of the current human interactome is composed of predicted moonlighting proteins. We found that disease related genes are over-represented among those candidates. Here, by comparing moonlighting candidates to non-candidates as groups, we further show that (i) they are significantly involved in more than one disease, (ii) they contribute to complex rather than monogenic diseases, (iii) the diseases in which they are involved are phenotypically different according to their annotations, finally, (iv) they are enriched for diseases pairs showing statistically significant comorbidity patterns based on Medicare records. Altogether, our results suggest that some observed comorbidities between phenotypically different diseases could be due to a shared protein involved in unrelated biological processes. PMID- 26157391 TI - Human liver myofibroblasts during development and diseases with a focus on portal (myo)fibroblasts. AB - Myofibroblasts are stromal cells mainly involved in tissue repair. These cells present contractile properties and play a major role in extracellular matrix deposition and remodeling. In liver, myofibroblasts are found in two critical situations. First, during fetal liver development, especially in portal tracts, myofibroblasts surround vessels and bile ducts during their maturation. After complete development of the liver, myofibroblasts disappear and are replaced in portal tracts by portal fibroblasts. Second, during liver injury, myofibroblasts re-appear principally deriving from the activation of local stromal cells such as portal fibroblasts and hepatic stellate cells or can sometimes emerge by an epithelial-mesenchymal transition process. After acute injury, myofibroblasts play also a major role during liver regeneration. While myofibroblastic precursor cells are well known, the spectrum of activation and the fate of myofibroblasts during disease evolution are not fully understood. Some data are in accordance with a possible deactivation, at least partial, or a disappearance by apoptosis. Despite these shadows, liver is definitively a pertinent model showing that myofibroblasts are pivotal cells for extracellular matrix control during morphogenesis, repair and fibrous scarring. PMID- 26157392 TI - Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W. AB - Congenital chloride diarrhea is an autosomal recessive disease caused by mutations in the intestinal lumenal membrane Cl(-)/HCO(-) 3 exchanger, SLC26A3. We report here the novel SLC26A3 mutation G393W in a Mexican child, the first such report in a patient from Central America. SLC26A3 G393W expression in Xenopus oocytes exhibits a mild hypomorphic phenotype, with normal surface expression and moderately reduced anion transport function. However, expression of HA-SLC26A3 in HEK-293 cells reveals intracellular retention and greatly decreased steady-state levels of the mutant polypeptide, in contrast to peripheral membrane expression of the wildtype protein. Whereas wildtype HA SLC26A3 is apically localized in polarized monolayers of filter-grown MDCK cells and Caco2 cells, mutant HA-SLC26A3 G393W exhibits decreased total polypeptide abundance, with reduced or absent surface expression and sparse punctate (or absent) intracellular distribution. The WT protein is similarly localized in LLC PK1 cells, but the mutant fails to accumulate to detectable levels. We conclude that the chloride-losing diarrhea phenotype associated with homozygous expression of SLC26A3 G393W likely reflects lack of apical surface expression in enterocytes, secondary to combined abnormalities in polypeptide trafficking and stability. Future progress in development of general or target-specific folding chaperonins and correctors may hold promise for pharmacological rescue of this and similar genetic defects in membrane protein targeting. PMID- 26157393 TI - Human odontoblast-like cells produce nitric oxide with antibacterial activity upon TLR2 activation. AB - The penetration of cariogenic oral bacteria into enamel and dentin during the caries process triggers an immune/inflammatory response in the underlying pulp tissue, the reduction of which is considered a prerequisite to dentinogenesis based pulp regeneration. If the role of odontoblasts in dentin formation is well known, their involvement in the antibacterial response of the dental pulp to cariogenic microorganisms has yet to be elucidated. Our aim here was to determine if odontoblasts produce nitric oxide (NO) with antibacterial activity upon activation of Toll-like receptor-2 (TLR2), a cell membrane receptor involved in the recognition of cariogenic Gram-positive bacteria. Human odontoblast-like cells differentiated from dental pulp explants were stimulated with the TLR2 synthetic agonist Pam2CSK4. We found that NOS1, NOS2, and NOS3 gene expression was increased in Pam2CSK4-stimulated odontoblast-like cells compared to unstimulated ones. NOS2 was the most up-regulated gene. NOS1 and NOS3 proteins were not detected in Pam2CSK4-stimulated or control cultures. NOS2 protein synthesis, NOS activity and NO extracellular release were all augmented in stimulated samples. Pam2CSK4-stimulated cell supernatants reduced Streptococcus mutans growth, an effect counteracted by the NOS inhibitor L-NAME. In vivo, the NOS2 gene was up-regulated in the inflamed pulp of carious teeth compared with healthy ones. NOS2 protein was immunolocalized in odontoblasts situated beneath the caries lesion but not in pulp cells from healthy teeth. These results suggest that odontoblasts may participate to the antimicrobial pulp response to dentin invading Gram-positive bacteria through NOS2-mediated NO production. They might in this manner pave the way for accurate dental pulp healing and regeneration. PMID- 26157394 TI - Caspase-1-mediated cytokine release from gestational tissues, placental, and cord blood. AB - Distinguishing between fetal and maternal inflammatory responses is necessary for understanding the immune interplay either side of the placenta. Fetal immunity reaches maturity during extrauterine life and while basic inflammatory responses afford a certain degree of protection, fetuses are vulnerable to infection. With the discovery of inflammasomes-intracellular scaffolds that facilitate the elaboration of reactions resulting in the release of mature interleukin-1beta (IL 1beta)-it is necessary to consider how inflammatory stimuli are processed. The purinergic P2X7 receptor located on haematopoietic cells is a key intermediary in signal transduction initiated at Toll-like receptors (TLR) terminating in release of the mature IL-1beta product. We demonstrate herein that IL-1beta release from fetal membranes and mononuclear cells isolated from cord, placental, and maternal blood, obtained at term, is P2X7- and caspase-1 dependent. The P2X7-dependent release of the cytokine, which was highest from choriodecidua, was attenuated by progesterone (P4), prolactin and an NFkB inhibitor. The NLRP3 inflammasome appears necessary for the processing of IL-1beta in gestational tissues and leukocytes. PMID- 26157395 TI - Treating Traumatized Offenders and Veterans by Means of Narrative Exposure Therapy. AB - Violent offenders and soldiers are at high risk of developing appetitive aggression and trauma-related disorders, which reduce successful integration into societies. Narrative exposure therapy (NET) for forensic offender rehabilitation (FORNET) aims at reducing symptoms of traumatic stress (e.g., posttraumatic stress disorder) and controlling readiness for aggressive behavior. It follows the logic of the evidence-based trauma-focused NET with special emphasis on violent acts in past and future behavior. In NET, the therapist guides the client by means of exposure through his traumatic experiences in chronological order linking the negative emotions, such as fear, shame, and disgust, to the past context and integrating the traumatic experiences into the autobiographical memory. During FORNET, we also encourage verbalization of any positive emotions and experiences linked to past violent and aggressive behaviors. This recall of positive emotions (linked to the there and then) is contrasted with feelings that emerge during the narration process (here and now). In this way, the therapist helps the client to anchor the whole range of sensory and bodily experiences, cognitions, and emotions to the contextual cues. Over the process of the therapy, we support the client to begin the role change from a violent offender to a citizen, who is capable of living a non-violent and socially adjusted life. Finally, the client develops visions and wishes for the future to support a successful integration into society. Several studies with veterans and violent youths have proven the feasibility of FORNET, found evidence of a positive outcome (recovered mental health, fewer offenses committed, less drug intake, and improved integration into civil society), and highlighted the importance of addressing the whole range of experiences while treating violent offenders or veterans. PMID- 26157397 TI - Natural frequencies facilitate diagnostic inferences of managers. AB - In Bayesian inference tasks, information about base rates as well as hit rate and false-alarm rate needs to be integrated according to Bayes' rule after the result of a diagnostic test became known. Numerous studies have found that presenting information in a Bayesian inference task in terms of natural frequencies leads to better performance compared to variants with information presented in terms of probabilities or percentages. Natural frequencies are the tallies in a natural sample in which hit rate and false-alarm rate are not normalized with respect to base rates. The present research replicates the beneficial effect of natural frequencies with four tasks from the domain of management, and with management students as well as experienced executives as participants. The percentage of Bayesian responses was almost twice as high when information was presented in natural frequencies compared to a presentation in terms of percentages. In contrast to most tasks previously studied, the majority of numerical responses were lower than the Bayesian solutions. Having heard of Bayes' rule prior to the study did not affect Bayesian performance. An implication of our work is that textbooks explaining Bayes' rule should teach how to represent information in terms of natural frequencies instead of how to plug probabilities or percentages into a formula. PMID- 26157396 TI - Increased Amplitude of Low Frequency Fluctuations but Normal Hippocampal-Default Mode Network Connectivity in Schizophrenia. AB - BACKGROUND: Clinical and preclinical studies have established that the hippocampus is hyperactive in schizophrenia, making it a possible biomarker for drug development. Increased hippocampal connectivity, which can be studied conveniently with resting state imaging, has been proposed as a readily accessible corollary of hippocampal hyperactivity. Here, we tested the hypothesis that hippocampal activity and connectivity are increased in patients with schizophrenia. METHODS: Sixty-three schizophrenia patients and 71 healthy control subjects completed a resting state functional magnetic resonance imaging scan. We assessed hippocampal activity with the amplitude of low frequency fluctuations. We analyzed hippocampal functional connectivity with the default mode network using three common methods: group and single subject level independent component analysis, and seed-based functional connectivity. RESULTS: In patients with schizophrenia, we observed increased amplitude of low frequency fluctuations but normal hippocampal connectivity using independent component and seed-based analyses. CONCLUSION: Our results indicate that although intrinsic hippocampal activity may be increased in schizophrenia, this finding does not extend to functional connectivity. Neuroimaging methods that directly assess hippocampal activity may be more promising for the identification of a biomarker for schizophrenia. PMID- 26157399 TI - What makes a thriver? Unifying the concepts of posttraumatic and postecstatic growth. AB - The thriver model is a novel framework that unifies the concepts of posttraumatic and postecstatic growth. According to the model, it is not the quality of an event, but the way it is processed, that is critical for the occurrence of post event growth. The model proposes that meaning making, supportive relationships, and positive emotions facilitate growth processes after positive as well as traumatic experiences. The tenability of these propositions was investigated in two dissimilar cultures. In Study 1, participants from the USA (n = 555) and India (n = 599) answered an extended version of the Social Readjustment Rating Scale to rank the socioemotional impact of events. Results indicate that negative events are perceived as more impactful than positive ones in the USA, whereas the reverse is true in India. In Study 2, participants from the USA (n = 342) and India (n = 341) answered questions about the thriver model's main components. Results showed that posttraumatic and postecstatic growth are highly interrelated. All elements of the thriver model were key variables for the prediction of growth. Supportive relationships and positive emotions had a direct effect on growth, while meaning making mediated the direct effect of major life events. PMID- 26157398 TI - New perspectives for motivating better decisions in older adults. AB - Decision-making competence in later adulthood is affected by declines in cognitive skills, and age-related changes in affect and experience can sometimes compensate. However, recent findings suggest that age-related changes in motivation also affect the extent to which adults draw from experience, affect, and deliberative skills when making decisions. To date, relatively little attention has been given to strategies for addressing age-related changes in motivation to promote better decisions in older adults. To address this limitation, we draw from diverse literatures to suggest promising intervention strategies for motivating older recipients' motivation to make better decisions. We start by reviewing the life-span developmental literature, which suggests that older adults' motivation to put effort into decisions depends on the perceived personal relevance of decisions as well as their self-efficacy (i.e., confidence in applying their ability and knowledge). Next, we discuss two approaches from the health intervention design literature, the mental models approach and the patient activation approach, which aim to improve motivation for decision making by improving personal relevance or by building self-efficacy or confidence to use new information and skills. Using examples from these literatures, we discuss how to construct interventions to motivate good decisions in later adulthood. PMID- 26157400 TI - Structural constraints on pronoun binding and coreference: evidence from eye movements during reading. AB - A number of recent studies have investigated how syntactic and non-syntactic constraints combine to cue memory retrieval during anaphora resolution. In this paper we investigate how syntactic constraints and gender congruence interact to guide memory retrieval during the resolution of subject pronouns. Subject pronouns are always technically ambiguous, and the application of syntactic constraints on their interpretation depends on properties of the antecedent that is to be retrieved. While pronouns can freely corefer with non-quantified referential antecedents, linking a pronoun to a quantified antecedent is only possible in certain syntactic configurations via variable binding. We report the results from a judgment task and three online reading comprehension experiments investigating pronoun resolution with quantified and non-quantified antecedents. Results from both the judgment task and participants' eye movements during reading indicate that comprehenders freely allow pronouns to corefer with non quantified antecedents, but that retrieval of quantified antecedents is restricted to specific syntactic environments. We interpret our findings as indicating that syntactic constraints constitute highly weighted cues to memory retrieval during anaphora resolution. PMID- 26157402 TI - Reputational concerns, not altruism, motivate restraint when gambling with other people's money. AB - People may behave prosocially not only because they value the welfare of others, but also to protect their own reputation. We examined the separate roles of altruism and reputational concerns in moral-hazard gambling tasks, which allowed subjects to gamble with a partner's money. In Study 1, subjects who were told that their partner would see their choices were more prosocial. In Study 2, subjects were more prosocial to a single partner when their choices were transparent than when their choices were attributed to a third party. We conclude that reputational concerns are a key restraint on selfish exploitation under moral hazard. PMID- 26157401 TI - Dopamine D4 receptor polymorphism and sex interact to predict children's affective knowledge. AB - Affective knowledge, the ability to understand others' emotional states, is considered to be a fundamental part in efficient social interaction. Affective knowledge can be seen as related to cognitive empathy, and in the framework of theory of mind (ToM) as affective ToM. Previous studies found that cognitive empathy and ToM are heritable, yet little is known regarding the specific genes involved in individual variability in affective knowledge. Investigating the genetic basis of affective knowledge is important for understanding brain mechanisms underlying socio-cognitive abilities. The 7-repeat (7R) allele within the third exon of the dopamine D4 receptor gene (DRD4-III) has been a focus of interest, due to accumulated knowledge regarding its relevance to individual differences in social behavior. A recent study suggests that an interaction between the DRD4-III polymorphism and sex is associated with cognitive empathy among adults. We aimed to examine the same association in two childhood age groups. Children (N = 280, age 3.5 years, N = 283, age 5 years) participated as part of the Longitudinal Israel Study of Twins. Affective knowledge was assessed through children's responses to an illustrated story describing different emotional situations, told in a laboratory setting. The findings suggest a significant interaction between sex and the DRD4-III polymorphism, replicated in both age groups. Boy carriers of the 7R allele had higher affective knowledge scores than girls, whereas in the absence of the 7R there was no significant sex effect on affective knowledge. The results support the importance of DRD4-III polymorphism and sex differences to social development. Possible explanations for differences from adult findings are discussed, as are pathways for future studies. PMID- 26157403 TI - Preference bias of head orientation in choosing between two non-durables. AB - The goal of this study is to investigate how customers' gaze, head and body orientations reflect their choices. Although the relationship between human choice and gaze behavior has been well-studied, other behaviors such as head and body are unknown. We conducted a two-alternatives-forced-choice task to examine (1) whether preference bias, i.e., a positional bias in gaze, head and body toward the item that was later chosen, exists in choice, (2) when preference bias is observed and when prediction of the resulting choice becomes possible (3) whether human choice is affected when the body orientations are manipulated. We used real non-durable products (cheap snacks and clothing) on a shopping shelf. The results showed that there was a significant preference bias in head orientation at the beginning 1 s when the subjects stood straight toward the shelf, and that the head orientation was more biased toward the selected item than the gaze and the center of pressure at the ending 1 s. Manipulating body orientation did not affect the result of choice. The preference bias detected by observing the head orientation would be useful in marketing science for predicting customers' choice. PMID- 26157404 TI - Relational perceptions in high school physical education: teacher- and peer related predictors of female students' motivation, behavioral engagement, and social anxiety. AB - Although researchers have demonstrated the importance of interpersonal processes in school-based physical education (PE), there have been calls for further studies that account for multiple relational perspectives and provide a more holistic understanding of students' relational perceptions. Guided by principles outlined within self-determination theory and the tripartite efficacy model, our aim was to explore the ways in which students' perceptions about their teacher and classmates directly and/or indirectly predicted motivation, anxiety, and engagement in PE. A total of 374 female high-school students reported the extent to which their teachers and classmates independently (a) engaged in relatedness supportive behaviors, (b) satisfied their need for relatedness, and (c) were confident in their ability in PE (i.e., relation-inferred self-efficacy). Students also rated their motivation and anxiety regarding PE, and teachers provided ratings of in-class behavioral engagement for each student. Analyses demonstrated support for the predictive properties of both teacher- and peer focused perceptions. Students largely reported more positive motivational orientations when they held favorable perceptions regarding their teacher and peers, and autonomous motivation was in turn positively related to behavioral engagement ratings. These findings offer novel insight into the network of interpersonal appraisals that directly and indirectly underpins important in class outcomes in PE. PMID- 26157405 TI - The adaptive value associated with expressing and perceiving angry-male and happy female faces. AB - Facial expressions are valuable for conveying and understanding the inner thoughts and feelings of the expressor. However, the adaptive value associated with a specific expression on a male face is different from a female face. The present review uses a functional-evolutionary analysis to elucidate the evolutionary advantage in the expression and perception of angry-male and happy female faces over angry-female and happy-male faces. For the expressors, it is more advantageous for men to show angry facial expression as it signals dominance, averts aggression and deters mate poaching; it is more advantageous for women to display happy facial expression as it signals their willingness for childcare, tending and befriending. For the perceivers, those sensitive to angry men avoid being physically harmed while those sensitive to happy women gain social support. Extant evidence suggests that facial structure and cognitive mechanisms evolved to express and perceive angry-male and happy-female faces more efficiently compared to angry-female and happy-male faces. PMID- 26157406 TI - What exactly is Universal Grammar, and has anyone seen it? AB - Universal Grammar (UG) is a suspect concept. There is little agreement on what exactly is in it; and the empirical evidence for it is very weak. This paper critically examines a variety of arguments that have been put forward as evidence for UG, focussing on the three most powerful ones: universality (all human languages share a number of properties), convergence (all language learners converge on the same grammar in spite of the fact that they are exposed to different input), and poverty of the stimulus (children know things about language which they could not have learned from the input available to them). I argue that these arguments are based on premises which are either false or unsubstantiated. Languages differ from each other in profound ways, and there are very few true universals, so the fundamental crosslinguistic fact that needs explaining is diversity, not universality. A number of recent studies have demonstrated the existence of considerable differences in adult native speakers' knowledge of the grammar of their language, including aspects of inflectional morphology, passives, quantifiers, and a variety of more complex constructions, so learners do not in fact converge on the same grammar. Finally, the poverty of the stimulus argument presupposes that children acquire linguistic representations of the kind postulated by generative grammarians; constructionist grammars such as those proposed by Tomasello, Goldberg and others can be learned from the input. We are the only species that has language, so there must be something unique about humans that makes language learning possible. The extent of crosslinguistic diversity and the considerable individual differences in the rate, style and outcome of acquisition suggest that it is more promising to think in terms of a language-making capacity, i.e., a set of domain-general abilities, rather than an innate body of knowledge about the structural properties of the target system. PMID- 26157408 TI - Problems with the mapping of magic tricks. PMID- 26157407 TI - Genetic sensitivity to emotional cues, racial discrimination and depressive symptoms among African-American adolescent females. AB - Psychosocial stress, including stress resulting from racial discrimination (RD), has been associated with elevated depressive symptoms. However, individuals vary in their reactivity to stress, with some variability resulting from genetic differences. Specifically, genetic variation within the linked promoter region of the serotonin transporter gene (5-HTTLPR) is related to heightened reactivity to emotional environmental cues. Likewise, variations within this region may interact with stressful life events (e.g., discrimination) to influence depressive symptoms, but this has not been empirically examined in prior studies. The objective of this study was to examine whether variation in the 5-HTTLPR gene interacts with RD to predict depressive symptoms among a sample of African American adolescent females. Participants were 304 African-American adolescent females enrolled in a sexually transmitted disease prevention trial. Participants completed a baseline survey assessing psychosocial factors including RD (low vs. high) and depressive symptomatology (low vs. high) and provided a saliva sample for genotyping the risk polymorphism 5-HTTLPR (s allele present vs. not present). In a logistic regression model adjusting for psychosocial correlates of depressive symptoms, an interaction between RD and 5-HTTLPR group was significantly associated with depressive symptomatology (AOR = 3.79, 95% CI: 1.20 11.98, p = 0.02). Follow-up tests found that high RD was significantly associated with greater odds of high depressive symptoms only for participants with the s allele. RD and 5-HTTLPR status interact to differentially impact depressive symptoms among African-American adolescent females. Efforts to decrease depression among minority youth should include interventions which address RD and strengthen factors (e.g., coping, emotion regulation, building support systems) which protect youth from the psychological costs of discrimination. PMID- 26157409 TI - Eighteen-month-olds' memory interference and distraction in a modified A-not-B task is not associated with their anticipatory looking in a false-belief task. AB - Infants' performance in non-verbal false-belief tasks is often interpreted as if they have understood false beliefs. This view has been questioned by a recent account that explains infants' performance in non-verbal false-belief tasks as the result of susceptibility to memory interference and distraction. We tested this alternative account by investigating the relationship between infants' false belief understanding, susceptibility to memory interference and distraction, and general cognitive development in 18-month-old infants (N = 22). False-belief understanding was tested in an anticipatory looking paradigm of a standard false belief task. Susceptibility to memory interference and distraction was tested in a modified A-not-B task. Cognitive development was measured via the Mental Scale of the Bayley Scales of Infant Development. We did not find any relationship between infants' performance in the false-belief task and the A-not-B task, even after controlling for cognitive development. This study shows that there is no ubiquitous relation between susceptibility to memory interference and distraction and performance in a false-belief task in infancy. PMID- 26157410 TI - Discourse accessibility constraints in children's processing of object relative clauses. AB - Children's poor performance on object relative clauses has been explained in terms of intervention locality. This approach predicts that object relatives with a full DP head and an embedded pronominal subject are easier than object relatives in which both the head noun and the embedded subject are full DPs. This prediction is shared by other accounts formulated to explain processing mechanisms. We conducted a visual-world study designed to test the off-line comprehension and on-line processing of object relatives in German-speaking 5 year-olds. Children were tested on three types of object relatives, all having a full DP head noun and differing with respect to the type of nominal phrase that appeared in the embedded subject position: another full DP, a 1st- or a 3rd person pronoun. Grammatical skills and memory capacity were also assessed in order to see whether and how they affect children's performance. Most accurately processed were object relatives with 1st-person pronoun, independently of children's language and memory skills. Performance on object relatives with two full DPs was overall more accurate than on object relatives with 3rd-person pronoun. In the former condition, children with stronger grammatical skills accurately processed the structure and their memory abilities determined how fast they were; in the latter condition, children only processed accurately the structure if they were strong both in their grammatical skills and in their memory capacity. The results are discussed in the light of accounts that predict different pronoun effects like the ones we find, which depend on the referential properties of the pronouns. We then discuss which role language and memory abilities might have in processing object relatives with various embedded nominal phrases. PMID- 26157411 TI - Processing fluency hinders subsequent recollection: an electrophysiological study. AB - Although many behavioral studies have investigated the effect of processing fluency on subsequent recognition memory, little research has examined the neural mechanism of this phenomenon. The present study aimed to explore the electrophysiological correlates of the effects of processing fluency on subsequent recognition memory by using an event-related potential (ERP) approach. The masked repetition priming paradigm was used to manipulate processing fluency in the study phase, and the R/K paradigm was utilized to investigate which recognition memory process (familiarity or recollection) was affected by processing fluency in the test phase. Converging behavioral and ERP results indicated that increased processing fluency impaired subsequent recollection. Results from the analysis of ERP priming effects in the study phase indicated that increased perceptual processing fluency of object features, reflected by the N/P 190 priming effect, can hinder encoding activities, reflected by the LPC priming effect, which leads to worse subsequent recollection based recognition memory. These results support the idea that processing fluency can influence subsequent recognition memory and provide a potential neural mechanism underlying this effect. However, further studies are needed to examine whether processing fluency can affect subsequent familiarity. PMID- 26157412 TI - Early, but not late visual distractors affect movement synchronization to a temporal-spatial visual cue. AB - The ease of synchronizing movements to a rhythmic cue is dependent on the modality of the cue presentation: timing accuracy is much higher when synchronizing with discrete auditory rhythms than an equivalent visual stimulus presented through flashes. However, timing accuracy is improved if the visual cue presents spatial as well as temporal information (e.g., a dot following an oscillatory trajectory). Similarly, when synchronizing with an auditory target metronome in the presence of a second visual distracting metronome, the distraction is stronger when the visual cue contains spatial-temporal information rather than temporal only. The present study investigates individuals' ability to synchronize movements to a temporal-spatial visual cue in the presence of same modality temporal-spatial distractors. Moreover, we investigated how increasing the number of distractor stimuli impacted on maintaining synchrony with the target cue. Participants made oscillatory vertical arm movements in time with a vertically oscillating white target dot centered on a large projection screen. The target dot was surrounded by 2, 8, or 14 distractor dots, which had an identical trajectory to the target but at a phase lead or lag of 0, 100, or 200 ms. We found participants' timing performance was only affected in the phase-lead conditions and when there were large numbers of distractors present (8 and 14). This asymmetry suggests participants still rely on salient events in the stimulus trajectory to synchronize movements. Subsequently, distractions occurring in the window of attention surrounding those events have the maximum impact on timing performance. PMID- 26157413 TI - Controlling the message: preschoolers' use of information to teach and deceive others. AB - Effective communication entails the strategic presentation of information; good communicators present representative information to their listeners-information that is both consistent with the concept being communicated and also unlikely to support another concept a listener might consider. The present study examined whether preschool-age children effectively select information to manipulate others' semantic knowledge, by testing how children choose information to teach or deceive their listeners. Results indicate that preschoolers indeed effectively select information to meet some specific communicative goals. When asked to teach others, children selected information that effectively spanned the concept of interest and avoided overly restrictive or overly general information; when asked to deceive others, they selected information consistent with the intended deceptive messages under some circumstances. Thus, preschool children possess remarkable abilities to select the best information to manipulate what others believe. PMID- 26157414 TI - Studying social interactions through immersive virtual environment technology: virtues, pitfalls, and future challenges. AB - The goal of the present review is to explain how immersive virtual environment technology (IVET) can be used for the study of social interactions and how the use of virtual humans in immersive virtual environments can advance research and application in many different fields. Researchers studying individual differences in social interactions are typically interested in keeping the behavior and the appearance of the interaction partner constant across participants. With IVET researchers have full control over the interaction partners, can standardize them while still keeping the simulation realistic. Virtual simulations are valid: growing evidence shows that indeed studies conducted with IVET can replicate some well-known findings of social psychology. Moreover, IVET allows researchers to subtly manipulate characteristics of the environment (e.g., visual cues to prime participants) or of the social partner (e.g., his/her race) to investigate their influences on participants' behavior and cognition. Furthermore, manipulations that would be difficult or impossible in real life (e.g., changing participants' height) can be easily obtained with IVET. Beside the advantages for theoretical research, we explore the most recent training and clinical applications of IVET, its integration with other technologies (e.g., social sensing) and future challenges for researchers (e.g., making the communication between virtual humans and participants smoother). PMID- 26157415 TI - Enhancing "theory of mind" through behavioral synchrony. AB - Theory of mind refers to the abilities underlying the capacity to reason about one's own and others' mental states. This ability is critical for predicting and making sense of the actions of others, is essential for efficient communication, fosters social learning, and provides the foundation for empathic concern. Clearly, there is incredible value in fostering theory of mind. Unfortunately, despite being the focus of a wealth of research over the last 40 years relatively little is known about specific strategies for fostering social perspective taking abilities. We provide a discussion of the rationale for applying one specific strategy for fostering efficient theory of mind-that of engaging in "behavioral synchrony" (i.e., the act of keeping together in time with others). Culturally evolved collective rituals involving synchronous actions have long been held to act as social glue. Specifically, here we present how behavioral synchrony tunes our minds for reasoning about other minds in the process of fostering social coordination and cooperation, and propose that we can apply behavioral synchrony as a tool for enhancing theory of mind. PMID- 26157416 TI - On the interaction of speakers' voice quality, ambient noise and task complexity with children's listening comprehension and cognition. AB - Suboptimal listening conditions interfere with listeners' on-line comprehension. A degraded source signal, noise that interferes with sound transmission, and/or listeners' cognitive or linguistic limitations are examples of adverse listening conditions. Few studies have explored the interaction of these factors in pediatric populations. Yet, they represent an increasing challenge in educational settings. We will in the following report on our research and address the effect of adverse listening conditions pertaining to speakers' voices, background noise, and children's cognitive capacity on listening comprehension. Results from our studies clearly indicate that children risk underachieving both in formal assessments and in noisy class-rooms when an examiner or teacher speaks with a hoarse (dysphonic) voice. This seems particularly true when task complexity is low or when a child is approaching her/his limits of mastering a comprehension task. PMID- 26157417 TI - Cardiac Autonomic Dysfunction in Patients with Schizophrenia and Their Healthy Relatives - A Small Review. AB - The majority of excess mortality among people with schizophrenia seems to be caused by cardiovascular complications, and in particular, coronary heart disease. In addition, the prevalence of heart failure and arrhythmias is increased in this population. Reduced efferent vagal activity, which has been consistently described in these patients and their healthy first-degree relatives, might be one important mechanism contributing to their increased cardiac mortality. A decrease in heart rate variability and complexity was often shown in unmedicated patients when compared to healthy controls. In addition, faster breathing rates, accompanied by shallow breathing, seem to influence autonomic cardiac functioning in acute unmedicated patients substantially. Moreover, low-physical fitness is a further and independent cardiac risk factor present in this patient population. Interestingly, new studies describe chronotropic incompetence during physical exercise as an important additional risk factor in patients with schizophrenia. Some studies report a correlation of the autonomic imbalance with the degree of positive symptoms (i.e., delusions) and some with the duration of disease. The main body of psychiatric research is focused on mental aspects of the disease, thereby neglecting obvious physical health needs of these patients. Here, a joint effort is needed to design interventional strategies in everyday clinical settings to improve physical health and quality of life. PMID- 26157418 TI - Anatomical Location of the Mesencephalic Locomotor Region and Its Possible Role in Locomotion, Posture, Cataplexy, and Parkinsonism. AB - The mesencephalic (or midbrain) locomotor region (MLR) was first described in 1966 by Shik and colleagues, who demonstrated that electrical stimulation of this region induced locomotion in decerebrate (intercollicular transection) cats. The pedunculopontine tegmental nucleus (PPT) cholinergic neurons and midbrain extrapyramidal area (MEA) have been suggested to form the neuroanatomical basis for the MLR, but direct evidence for the role of these structures in locomotor behavior has been lacking. Here, we tested the hypothesis that the MLR is composed of non-cholinergic spinally projecting cells in the lateral pontine tegmentum. Our results showed that putative MLR neurons medial to the PPT and MEA in rats were non-cholinergic, glutamatergic, and express the orexin (hypocretin) type 2 receptors. Fos mapping correlated with motor behaviors revealed that the dorsal and ventral MLR are activated, respectively, in association with locomotion and an erect posture. Consistent with these findings, chemical stimulation of the dorsal MLR produced locomotion, whereas stimulation of the ventral MLR caused standing. Lesions of the MLR (dorsal and ventral regions together) resulted in cataplexy and episodic immobility of gait. Finally, trans neuronal tracing with pseudorabies virus demonstrated disynaptic input to the MLR from the substantia nigra via the MEA. These findings offer a new perspective on the neuroanatomic basis of the MLR, and suggest that MLR dysfunction may contribute to the postural and gait abnormalities in Parkinsonism. PMID- 26157419 TI - Editorial: "Thyroid Hormone in Brain and Brain Cells". PMID- 26157420 TI - The molecular dimension of microbial species: 1. Ecological distinctions among, and homogeneity within, putative ecotypes of Synechococcus inhabiting the cyanobacterial mat of Mushroom Spring, Yellowstone National Park. AB - Based on the Stable Ecotype Model, evolution leads to the divergence of ecologically distinct populations (e.g., with different niches and/or behaviors) of ecologically interchangeable membership. In this study, pyrosequencing was used to provide deep sequence coverage of Synechococcus psaA genes and transcripts over a large number of habitat types in the Mushroom Spring microbial mat. Putative ecological species [putative ecotypes (PEs)], which were predicted by an evolutionary simulation based on the Stable Ecotype Model (Ecotype Simulation), exhibited distinct distributions relative to temperature-defined positions in the effluent channel and vertical position in the upper 1 mm-thick mat layer. Importantly, in most cases variants predicted to belong to the same PE formed unique clusters relative to temperature and depth in the mat in canonical correspondence analysis, supporting the hypothesis that while the PEs are ecologically distinct, the members of each ecotype are ecologically homogeneous. PEs responded differently to experimental perturbations of temperature and light, but the genetic variation within each PE was maintained as the relative abundances of PEs changed, further indicating that each population responded as a set of ecologically interchangeable individuals. Compared to PEs that predominate deeper within the mat photic zone, the timing of transcript abundances for selected genes differed for PEs that predominate in microenvironments closer to upper surface of the mat with spatiotemporal differences in light and O2 concentration. All of these findings are consistent with the hypotheses that Synechococcus species in hot spring mats are sets of ecologically interchangeable individuals that are differently adapted, that these adaptations control their distributions, and that the resulting distributions constrain the activities of the species in space and time. PMID- 26157421 TI - Microbial- and thiosulfate-mediated dissolution of mercury sulfide minerals and transformation to gaseous mercury. AB - Mercury (Hg) is a toxic heavy metal that poses significant environmental and human health risks. Soils and sediments, where Hg can exist as the Hg sulfide mineral metacinnabar (beta-HgS), represent major Hg reservoirs in aquatic environments. Metacinnabar has historically been considered a sink for Hg in all but severely acidic environments, and thus disregarded as a potential source of Hg back to aqueous or gaseous pools. Here, we conducted a combination of field and laboratory incubations to identify the potential for metacinnabar as a source of dissolved Hg within near neutral pH environments and the underpinning (a)biotic mechanisms at play. We show that the abundant and widespread sulfur oxidizing bacteria of the genus Thiobacillus extensively colonized metacinnabar chips incubated within aerobic, near neutral pH creek sediments. Laboratory incubations of axenic Thiobacillus thioparus cultures led to the release of metacinnabar-hosted Hg(II) and subsequent volatilization to Hg(0). This dissolution and volatilization was greatly enhanced in the presence of thiosulfate, which served a dual role by enhancing HgS dissolution through Hg complexation and providing an additional metabolic substrate for Thiobacillus. These findings reveal a new coupled abiotic-biotic pathway for the transformation of metacinnabar-bound Hg(II) to Hg(0), while expanding the sulfide substrates available for neutrophilic chemosynthetic bacteria to Hg-laden sulfides. They also point to mineral-hosted Hg as an underappreciated source of gaseous elemental Hg to the environment. PMID- 26157422 TI - Anaerobic digestion of the microalga Spirulina at extreme alkaline conditions: biogas production, metagenome, and metatranscriptome. AB - A haloalkaline anaerobic microbial community obtained from soda lake sediments was used to inoculate anaerobic reactors for the production of methane rich biogas. The microalga Spirulina was successfully digested by the haloalkaline microbial consortium at alkaline conditions (pH 10, 2.0 M Na(+)). Continuous biogas production was observed and the obtained biogas was rich in methane, up to 96%. Alkaline medium acted as a CO2 scrubber which resulted in low amounts of CO2 and no traces of H2S in the produced biogas. A hydraulic retention time (HRT) of 15 days and 0.25 g Spirulina L(-1) day(-1) organic loading rate (OLR) were identified as the optimal operational parameters. Metagenomic and metatranscriptomic analysis showed that the hydrolysis of the supplied substrate was mainly carried out by Bacteroidetes of the "ML635J-40 aquatic group" while the hydrogenotrophic pathway was the main producer of methane in a methanogenic community dominated by Methanocalculus. PMID- 26157423 TI - Metabolic transition in mycorrhizal tomato roots. AB - Beneficial plant-microorganism interactions are widespread in nature. Among them, the symbiosis between plant roots and arbuscular mycorrhizal fungi (AMF) is of major importance, commonly improving host nutrition and tolerance against environmental and biotic challenges. Metabolic changes were observed in a well established symbiosis between tomato and two common AMF: Rhizophagus irregularis and Funneliformis mosseae. Principal component analysis of metabolites, determined by non-targeted liquid chromatography-mass spectrometry, showed a strong metabolic rearrangement in mycorrhizal roots. There was generally a negative impact of mycorrhizal symbiosis on amino acid content, mainly on those involved in the biosynthesis of phenylpropanoids. On the other hand, many intermediaries in amino acid and sugar metabolism and the oxylipin pathway were among the compounds accumulating more in mycorrhizal roots. The metabolic reprogramming also affected other pathways in the secondary metabolism, mainly phenyl alcohols (lignins and lignans) and vitamins. The results showed that source metabolites of these pathways decreased in mycorrhizal roots, whilst the products derived from alpha-linolenic and amino acids presented higher concentrations in AMF-colonized roots. Mycorrhization therefore increased the flux into those pathways. Venn-diagram analysis showed that there are many induced signals shared by both mycorrhizal interactions, pointing to general mycorrhiza-associated changes in the tomato metabolome. Moreover, fungus-specific fingerprints were also found, suggesting that specific molecular alterations may underlie the reported functional diversity of the symbiosis. Since most positively regulated pathways were related to stress response mechanisms, their potential contribution to improved host stress tolerance is discussed. PMID- 26157424 TI - Mechanisms of pressure-mediated cell death and injury in Escherichia coli: from fundamentals to food applications. AB - High hydrostatic pressure is commercially applied to extend the shelf life of foods, and to improve food safety. Current applications operate at ambient temperature and 600 MPa or less. However, bacteria that may resist this pressure level include the pathogens Staphylococcus aureus and strains of Escherichia coli, including shiga-toxin producing E. coli. The resistance of E. coli to pressure is variable between strains and highly dependent on the food matrix. The targeted design of processes for the safe elimination of E. coli thus necessitates deeper insights into mechanisms of interaction and matrix-strain interactions. Cellular targets of high pressure treatment in E. coli include the barrier properties of the outer membrane, the integrity of the cytoplasmic membrane as well as the activity of membrane-bound enzymes, and the integrity of ribosomes. The pressure-induced denaturation of membrane bound enzymes results in generation of reactive oxygen species and subsequent cell death caused by oxidative stress. Remarkably, pressure resistance at the single cell level relates to the disposition of misfolded proteins in inclusion bodies. While the pressure resistance E. coli can be manipulated by over-expression or deletion of (stress) proteins, the mechanisms of pressure resistance in wild type strains is multi-factorial and not fully understood. This review aims to provide an overview on mechanisms of pressure-mediated cell death in E. coli, and the use of this information for optimization of high pressure processing of foods. PMID- 26157425 TI - Occurrence of classes I and II integrons in Enterobacteriaceae collected from Zagazig University Hospitals, Egypt. AB - Integrons are genetic units characterized by the ability to capture and incorporate gene cassettes, thus can contribute to the emergence and transfer of antibiotic resistance. The objectives of this study were: (1) to investigate the presence and distribution of class I and class II integrons and the characteristics of the gene cassettes they carry in Enterobacteriaceae isolated from nosocomial infections at Zagzig University Hospital in Egypt, (2) to determine their impact on resistance, and (3) to identify risk factors for the existence of integrons. Relevant samples and full clinical history were collected from 118 inpatients. Samples were processed; isolated microbes were identified and tested for antibiotic susceptibilities. Integrons were detected by polymerase chain reaction (PCR) and were characterized into class I or II by restriction fragment length polymorphism (RFLP). Integron-positive isolates were subjected to another PCR to detect gene cassette, followed by gene cassette sequencing. Risk factors were analyzed by logistic regression analysis. Seventy-six Enterobacteriaceae isolates were recognized, 41 of them (53.9%) were integron positive; 39 strains carried class I and 2 strains carried class II integrons. Integrons had gene cassettes encoding different combinations and types of resistance determinants. Interestingly, blaOXA129 gene was found and ereA gene was carried on class I integrons. The same determinants were carried within isolates of the same species as well as isolates of different species. The presence of integrons was significantly associated with multidrug resistance (MDR). No risk factors were associated for integron carriage. We conclude that integrons carrying gene cassettes encoding antibiotic resistance are significantly present among Enterobacteriaceae causing nosocomial infection in our hospital. Risk factors for acquisition remain to be identified. PMID- 26157426 TI - Serotypes and antimicrobial susceptibility of Salmonella spp. isolated from farm animals in China. AB - Salmonella spp. can indirectly infect humans via transfer from animals and animal derived food products, and thereby cause potentially fatal diseases. Therefore, gaining an understanding of Salmonella infection in farm animals is increasingly important. The aim of this study was to identify the distribution of serotypes in Salmonella samples isolated from chickens (n = 837), pigs (n = 930), and dairy cows (n = 418) in central China (Henan, Hubei, and Hunan provinces) in 2010-2011, and investigate the susceptibility of strains to antimicrobial agents. Salmonella isolates were identified by PCR amplification of the invA gene, serotypes were determined by using a slide agglutination test for O and H antigens, and susceptibility to 24 antimicrobials was tested using the agar dilution method. In total, 248 Salmonella strains were identified: 105, 105, and 38 from chickens, dairy cows, and pigs, respectively. Additionally, 209 strains were identified in diseased pigs from the Huazhong Agricultural University veterinary hospital. Among these 457 strains, the dominant serotypes were Typhimurium in serogroup B, IIIb in serogroup C, and Enteritidis in serogroup D. In antimicrobial susceptibility tests, 41.14% of Salmonella spp. were susceptible to all antimicrobial agents, 48.14% were resistant to at least one, and 34.72% were resistant to more than three classes. Strains were highly resistant to sulfamethoxazole-trimethoprim (39.61%), nalidixic acid (39.17%), doxycycline (28.22%), and tetracycline (27.58%). Resistance to cephalosporins and fluoroquinolones ranged from 5.25 to 7.44% and 19.04 to 24.51%, respectively. Among penicillin-resistant and cephalosporin-resistant strains, 25 isolates produced extended-spectrum beta-lactamases (ESBLs). The multidrug-resistant and ESBL-producing Salmonella strains identified in healthy animals here will present a challenge for veterinary medicine and farm animal husbandry, and could also pose a threat to public health. The level of antibiotic resistance observed in this study further highlights the need for careful and selective use of antibiotics. PMID- 26157427 TI - Development of cell differentiation in the transition to multicellularity: a dynamical modeling approach. AB - Multicellularity has emerged and continues to emerge in a variety of lineages and under diverse environmental conditions. In order to attain individuality and integration, multicellular organisms must exhibit spatial cell differentiation, which in turn allows cell aggregates to robustly generate traits and behaviors at the multicellular level. Nevertheless, the mechanisms that may lead to the development of cellular differentiation and patterning in emerging multicellular organisms remain unclear. We briefly review two conceptual frameworks that have addressed this issue: the cooperation-defection framework and the dynamical patterning modules (DPMs) framework. Then, situating ourselves in the DPM formalism first put forward by S. A. Newman and collaborators, we state a hypothesis for cell differentiation and arrangement in cellular masses of emerging multicellular organisms. Our hypothesis is based on the role of the generic cell-to-cell communication and adhesion patterning mechanisms, which are two fundamental mechanisms for the evolution of multicellularity, and whose molecules seem to be well-conserved in extant multicellular organisms and their unicellular relatives. We review some fundamental ideas underlying this hypothesis and contrast them with empirical and theoretical evidence currently available. Next, we use a mathematical model to illustrate how the mechanisms and assumptions considered in the hypothesis we postulate may render stereotypical arrangements of differentiated cells in an emerging cellular aggregate and may contribute to the variation and recreation of multicellular phenotypes. Finally, we discuss the potential implications of our approach and compare them to those entailed by the cooperation-defection framework in the study of cell differentiation in the transition to multicellularity. PMID- 26157428 TI - The molecular dimension of microbial species: 3. Comparative genomics of Synechococcus strains with different light responses and in situ diel transcription patterns of associated putative ecotypes in the Mushroom Spring microbial mat. AB - Genomes were obtained for three closely related strains of Synechococcus that are representative of putative ecotypes (PEs) that predominate at different depths in the 1 mm-thick, upper-green layer in the 60 degrees C mat of Mushroom Spring, Yellowstone National Park, and exhibit different light adaptation and acclimation responses. The genomes were compared to the published genome of a previously obtained, closely related strain from a neighboring spring, and differences in both gene content and orthologous gene alleles between high-light-adapted and low light-adapted strains were identified. Evidence of genetic differences that relate to adaptation to light intensity and/or quality, CO2uptake, nitrogen metabolism, organic carbon metabolism, and uptake of other nutrients were found between strains of the different putative ecotypes. In situ diel transcription patterns of genes, including genes unique to either low-light-adapted or high light-adapted strains and different alleles of an orthologous photosystem gene, revealed that expression is fine-tuned to the different light environments experienced by ecotypes prevalent at various depths in the mat. This study suggests that strains of closely related PEs have different genomic adaptations that enable them to inhabit distinct ecological niches while living in close proximity within a microbial community. PMID- 26157429 TI - PE11 (Rv1169c) selectively alters fatty acid components of Mycobacterium smegmatis and host cell interleukin-6 level accompanied with cell death. AB - PE/PPE family proteins, named after their conserved PE (Pro-Glu) and PPE (Pro-Pro Glu) domains of N-terminal, are most intriguing aspects of pathologic mycobacterial genome. The roles of most members of this family remain unknown, although selected genes of this family are related to the virulence of Mycobacterium tuberculosis. In order to decipher the role of Rv1169c, the Mycobacterium smegmatis strain heterologous expressed this ORF was constructed and identified that Rv1169c was a cell wall associated protein with a novel function in modifying the cell wall fatty acids. The growth of Rv1169c expressing strain was affected under surface stress, acidic condition and antibiotics treatment. M. smegmatis expressing Rv1169c induced necrotic cell death of macrophage after infection and significantly decreased interlukin-6 production compared to controls. In general, these results underscore a proposing role of Rv1169c in virulence of M. tuberculosis, as it's role in the susceptibility of anti-mycobacteria factors caused by modified cell wall fatty acid, and the induced necrotic cell death by Rv1169c is crucial for M. tuberculosis virulence during infection. PMID- 26157430 TI - HIV-1 gp120 and morphine induced oxidative stress: role in cell cycle regulation. AB - HIV infection and illicit drugs are known to induce oxidative stress and linked with severity of viral replication, disease progression, impaired cell cycle regulation and neurodegeneration. Studies have shown that morphine accelerates HIV infection and disease progression mediated by Reactive oxygen species (ROS). Oxidative stress impact redox balance and ROS production affect cell cycle regulation. However, the role of morphine in HIV associated acceleration of oxidative stress and its link to cell cycle regulation and neurodegeneration has not been elucidated. The aim of present study is to elucidate the mechanism of oxidative stress induced glutathione synthases (GSS), super oxide dismutase (SOD), and glutathione peroxidase (GPx) impact cell cycle regulated protein cyclin-dependent kinase 1, cell division cycle 2 (CDK-1/CDC-2), cyclin B, and cell division cycle 25C (CDC-25C) influencing neuronal dysfunction by morphine co morbidity with HIV-1 gp120. It was observed that redox imbalance inhibited the GSS, GPx and increased SOD which, subsequently inhibited CDK-1/CDC-2 whereas cyclin B and CDC-25C significantly up regulated in HIV-1 gp120 with morphine compared to either HIV-1 gp120 or morphine treated alone in human microglial cell line. These results suggest that HIV positive morphine users have increased levels of oxidative stress and effect of cell cycle machinery, which may cause the HIV infection and disease progression. PMID- 26157431 TI - Analyzing the antagonistic potential of the lichen microbiome against pathogens by bridging metagenomic with culture studies. AB - Naturally occurring antagonists toward pathogens play an important role to avoid pathogen outbreaks in ecosystems, and they can be applied as biocontrol agents for crops. Lichens present long-living symbiotic systems continuously exposed to pathogens. To analyze the antagonistic potential in lichens, we studied the bacterial community active against model bacteria and fungi by an integrative approach combining isolate screening, omics techniques, and high resolution mass spectrometry. The highly diverse microbiome of the lung lichen [Lobaria pulmonaria (L.) Hoffm.] included an abundant antagonistic community dominated by Stenotrophomonas, Pseudomonas, and Burkholderia. While antagonists represent 24.5% of the isolates, they were identified with only 7% in the metagenome; which means that they were overrepresented in the culturable fraction. Isolates of the dominant antagonistic genus Stenotrophomonas produced spermidine as main bioactive component. Moreover, spermidine-related genes, especially for the transport, were identified in the metagenome. The majority of hits identified belonged to Alphaproteobacteria, while Stenotrophomonas-specific spermidine synthases were not present in the dataset. Evidence for plant growth promoting effects was found for lichen-associated strains of Stenotrophomonas. Linking of metagenomic and culture data was possible but showed partly contradictory results, which required a comparative assessment. However, we have shown that lichens are important reservoirs for antagonistic bacteria, which open broad possibilities for biotechnological applications. PMID- 26157432 TI - Electron transport phosphorylation in rumen butyrivibrios: unprecedented ATP yield for glucose fermentation to butyrate. AB - From a genomic analysis of rumen butyrivibrios (Butyrivibrio and Pseudobutyrivibrio sp.), we have re-evaluated the contribution of electron transport phosphorylation (ETP) to ATP formation in this group. This group is unique in that most (76%) genomes were predicted to possess genes for both Ech and Rnf transmembrane ion pumps. These pumps act in concert with the NifJ and Bcd Etf to form a electrochemical potential (DeltaMUH(+) and DeltaMUNa(+)), which drives ATP synthesis by ETP. Of the 62 total butyrivibrio genomes currently available from the Hungate 1000 project, all 62 were predicted to possess NifJ, which reduces oxidized ferredoxin (Fdox) during pyruvate conversion to acetyl CoA. All 62 possessed all subunits of Bcd-Etf, which reduces Fdox and oxidizes reduced NAD during crotonyl-CoA reduction. Additionally, 61 genomes possessed all subunits of the Rnf, which generates DeltaMUH(+) or DeltaMUNa(+) from oxidation of reduced Fd (Fdred) and reduction of oxidized NAD. Further, 47 genomes possessed all six subunits of the Ech, which generates DeltaMUH(+) from oxidation of Fdred. For glucose fermentation to butyrate and H2, the electrochemical potential established should drive synthesis of ~1.5 ATP by the F0F1-ATP synthase (possessed by all 62 genomes). The total yield is ~4.5 ATP/glucose after accounting for three ATP formed by classic substrate-level phosphorylation, and it is one the highest yields for any glucose fermentation. The yield was the same when unsaturated fatty acid bonds, not H(+), served as the electron acceptor (as during biohydrogenation). Possession of both Ech and Rnf had been previously documented in only a few sulfate-reducers, was rare in other rumen prokaryotic genomes in our analysis, and may confer an energetic advantage to rumen butyrivibrios. This unique energy conservation system might enhance the butyrivibrios' ability to overcome growth inhibition by unsaturated fatty acids, as postulated herein. PMID- 26157433 TI - Combinatorial synthesis and screening of cancer cell-specific nanomedicines targeted via phage fusion proteins. AB - Active tumor targeting of nanomedicines has recently shown significant improvements in the therapeutic activity of currently existing drug delivery systems, such as liposomal doxorubicin (Doxil/Caelyx/Lipodox). Previously, we have shown that isolated pVIII major coat proteins of the fd-tet filamentous phage vector, containing cancer cell-specific peptide fusions at their N terminus, can be used as active targeting ligands in a liposomal doxorubicin delivery system in vitro and in vivo. Here, we show a novel major coat protein isolation procedure in 2-propanol that allows spontaneous incorporation of the hydrophobic protein core into preformed liposomal doxorubicin with minimal damage or drug loss while still retaining the targeting ligand exposed for cell-specific targeting. Using a panel of 12 structurally unique ligands with specificity toward breast, lung, and/or pancreatic cancer, we showed the feasibility of pVIII major coat proteins to significantly increase the throughput of targeting ligand screening in a common nanomedicine core. Phage protein-modified Lipodox samples showed an average doxorubicin recovery of 82.8% across all samples with 100% of protein incorporation in the correct orientation (N-terminus exposed). Following cytotoxicity screening in a doxorubicin-sensitive breast cancer line (MCF-7), three major groups of ligands were identified. Ligands showing the most improved cytotoxicity included: DMPGTVLP, ANGRPSMT, VNGRAEAP, and ANDVYLD showing a 25 fold improvement (p < 0.05) in toxicity. Similarly DGQYLGSQ, ETYNQPYL, and GSSEQLYL ligands with specificity toward a doxorubicin-insensitive pancreatic cancer line (PANC-1) showed significant increases in toxicity (2-fold; p < 0.05). Thus, we demonstrated proof-of-concept that pVIII major coat proteins can be screened in significantly higher throughput to identify novel ligands displaying improved therapeutic activity in a desired cancer phenotype. PMID- 26157435 TI - Changes in gene expression of Prymnesium parvum induced by nitrogen and phosphorus limitation. AB - Prymnesium parvum is a globally distributed prymnesiophyte alga commonly found in brackish water marine ecosystems and lakes. It possesses a suite of toxins with ichthyotoxic, cytotoxic and hemolytic effects which, along with its mixotrophic nutritional capabilities, allows it to form massive Ecosystem Disruptive Algal Blooms (EDABs). While blooms of high abundance coincide with high levels of nitrogen (N) and phosphorus (P), reports of field and laboratory studies have noted that P. parvum toxicity appears to be augmented at high N:P ratios or P limiting conditions. Here we present the results of a comparative analysis of P. parvum RNA-Seq transcriptomes under nutrient replete conditions, and N or P deficiency to understand how this organism responds at the transcriptional level to varying nutrient conditions. In nutrient limited conditions we found diverse transcriptional responses for genes involved in nutrient uptake, protein synthesis and degradation, photosynthesis, and toxin production. As anticipated, when either N or P was limiting, transcription levels of genes encoding transporters for the respective nutrient were higher than those under replete condition. Ribosomal and lysosomal protein genes were expressed at higher levels under either nutrient-limited condition compared to the replete condition. Photosynthesis genes and polyketide synthase genes were more highly expressed under P-limitation but not under N-limitation. These results highlight the ability of P. parvum to mount a coordinated and varied cellular and physiological response to nutrient limitation. Results also provide potential marker genes for further evaluating the physiological response and toxin production of P. parvum populations during bloom formation or to changing environmental conditions. PMID- 26157434 TI - The absence of the Pseudomonas aeruginosa OprF protein leads to increased biofilm formation through variation in c-di-GMP level. AB - OprF is the major outer membrane porin in bacteria belonging to the Pseudomonas genus. In previous studies, we have shown that OprF is required for full virulence expression of the opportunistic pathogen Pseudomonas aeruginosa. Here, we describe molecular insights on the nature of this relationship and report that the absence of OprF leads to increased biofilm formation and production of the Pel exopolysaccharide. Accordingly, the level of c-di-GMP, a key second messenger in biofilm control, is elevated in an oprF mutant. By decreasing c-di-GMP levels in this mutant, both biofilm formation and pel gene expression phenotypes were restored to wild-type levels. We further investigated the impact on two small RNAs, which are associated with the biofilm lifestyle, and found that expression of rsmZ but not of rsmY was increased in the oprF mutant and this occurs in a c di-GMP-dependent manner. Finally, the extracytoplasmic function (ECF) sigma factors AlgU and SigX displayed higher activity levels in the oprF mutant. Two genes of the SigX regulon involved in c-di-GMP metabolism, PA1181 and adcA (PA4843), were up-regulated in the oprF mutant, partly explaining the increased c di-GMP level. We hypothesized that the absence of OprF leads to a cell envelope stress that activates SigX and results in a c-di-GMP elevated level due to higher expression of adcA and PA1181. The c-di-GMP level can in turn stimulate Pel synthesis via increased rsmZ sRNA levels and pel mRNA, thus affecting Pel dependent phenotypes such as cell aggregation and biofilm formation. This work highlights the connection between OprF and c-di-GMP regulatory networks, likely via SigX (ECF), on the regulation of biofilm phenotypes. PMID- 26157436 TI - The Cryptococcus neoformans capsule: lessons from the use of optical tweezers and other biophysical tools. AB - The fungal pathogen Cryptococcus neoformans causes life-threatening infections in immunocompromised individuals, representing one of the leading causes of morbidity and mortality in AIDS patients. The main virulence factor of C. neoformans is the polysaccharide capsule; however, many fundamental aspects of capsule structure and function remain poorly understood. Recently, important capsule properties were uncovered using optical tweezers and other biophysical techniques, including dynamic and static light scattering, zeta potential and viscosity analysis. This review provides an overview of the latest findings in this emerging field, explaining the impact of these findings on our understanding of C. neoformans biology and resistance to host immune defenses. PMID- 26157437 TI - High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo. AB - Although high-dose rifampicin holds promise for improving tuberculosis control by potentially shortening treatment duration, these effects attributed to eradication of persistent bacteria are unclear. The presence of persistent Mycobacterium tuberculosis was examined using resuscitation promoting factors (RPFs) in both in vitro hypoxia and in vivo murine tuberculosis models before and after treatment with incremental doses of rifampicin. Pharmacokinetic parameters and dose-dependent profile of rifampicin in the murine model were determined. The Cornell mouse model was used to test efficacy of high-dose rifampicin in combination with isoniazid and pyrazinamide and to measure relapse rate. There were large numbers of RPF-dependent persisters in vitro and in vivo. Stationary phase cultures were tolerant to rifampicin while higher concentrations of rifampicin eradicated plate count positive but not RPF-dependent persistent bacteria. In murine infection model, incremental doses of rifampicin exhibited a dose-dependent eradication of RPF-dependent persisters. Increasing the dose of rifampicin significantly reduced the risk of antibiotic resistance emergence. In Cornell model, mice treated with high-dose rifampicin regimen resulted in faster visceral clearance; organs were M. tuberculosis free 8 weeks post-treatment compared to 14 weeks with standard-dose rifampicin regimen. Organ sterility, plate count and RPF-dependent persister negative, was achieved. There was no disease relapse compared to the standard dose regimen (87.5%). High-dose rifampicin therapy results in eradication of RPF-dependent persisters, allowing shorter treatment duration without disease relapse. Optimizing rifampicin to its maximal efficacy with acceptable side-effect profiles will provide valuable information in human studies and can potentially improve current tuberculosis chemotherapy. PMID- 26157438 TI - Emergent Transcriptomic Technologies and Their Role in the Discovery of Biomarkers of Liver Transplant Tolerance. AB - Liver transplantation offers a unique window into transplant immunology due, in part, to the considerable proportion of recipients who develop immunological tolerance to their allograft. Biomarkers are able to identify and predict such a state of tolerance, and thereby able to establish suitable candidates for the minimization of hazardous immunosuppressive therapies, are not only of great potential clinical benefit but might also shed light on the immunological mechanisms underlying tolerance and rejection. Here, we review the emergent transcriptomic technologies serving as drivers of biomarker discovery, we appraise efforts to identify a molecular signature of liver allograft tolerance, and we consider the implications of this work on the mechanistic understanding of immunological tolerance. PMID- 26157439 TI - The Importance of Autoantibody Detection in Primary Biliary Cirrhosis. PMID- 26157440 TI - Corrigendum: Liver-Stage Specific Response among Endemic Populations: Diet and Immunity. AB - [This corrects the article on p. 125 in vol. 6, PMID: 25852693.]. PMID- 26157441 TI - Corrigendum: CD90(+) Stromal Cells are Non-Professional Innate Immune Effectors of the Human Colonic Mucosa. AB - [This corrects the article on p. 307 in vol. 4, PMID: 24137162.]. PMID- 26157442 TI - Editorial: Paradigm Changes are Required in HIV Vaccine Research. PMID- 26157443 TI - Transcriptomic landscape of Pueraria lobata demonstrates potential for phytochemical study. AB - Pueraria lobata (Willd.) Ohwi has a long and broad application in the treatment of disease. However, in the US and EU, it is treated as a notorious weed. The information to be gained from decoding the deep transcriptome profile would facilitate further research on P. lobata. In this study, more than 93 million fastq format reads were generated by Illumina's next-generation sequencing approach using five types of P. lobata tissue, followed by CLC de novo assembly methods, ultimately yielding about 83,041 contigs in total. Then BLASTx similarity searches against the NCBI NR database and UniProtKB database were conducted. Once the duplicates among BLASTx hits were eliminated, ID mapping against the UniProt database was conducted online to retrieve Gene Ontology information. In search of the putative genes relevant to essential biosynthesis pathways, all 1,348 unique enzyme commission numbers were used to map pathways against the Kyoto Encyclopedia of Genes and Genomes. Enzymes related to the isoflavonoid and flavonoid biosynthesis pathways were focused for detailed investigation and subsequently, quantitative real-time reverse transcription polymerase chain reaction was conducted for biological validation. Metabolites of interest, puerarin and daidzin were studied by HPLC. The findings in this report may serve as a footstone for further research into this promising medicinal plant. PMID- 26157444 TI - TCP24 modulates secondary cell wall thickening and anther endothecium development. AB - miR319-targeted TCP genes are believed to regulate cell division in leaves and floral organs. However, it remains unknown whether these genes are involved in cell wall development. Here, we report that TCP24 negatively regulates secondary wall thickening in floral organs and roots. The overexpression of the miR319a resistant version of TCP24 in Arabidopsis disrupted the thickening of secondary cell walls in the anther endothecium, leading to male sterility because of arrested anther dehiscence and pollen release. Several genes linked to secondary cell wall biogenesis and thickening were down-regulated in these transgenic plants. By contrast, the inhibition of TCP24 using the ectopic expression of a TCP24-SRDX repressor fusion protein, or the silencing of TCP genes by miR319a overexpression, increased cell wall lignification and the enhanced secondary cell wall thickening. Our results suggest that TCP24 acts as an important regulator of secondary cell wall thickening and modulates anther endothecium development. PMID- 26157445 TI - Soil versus foliar iodine fertilization as a biofortification strategy for field grown vegetables. AB - Iodine (I) biofortification of vegetables by means of soil and foliar applications was investigated in field experiments on a sandy loam soil. Supply of iodine to the soil in trial plots fertilized with potassium iodide (KI) and potassium iodate directly before planting (0, 1.0, 2.5, 7.5, and 15 kg I ha(-1)) increased the iodine concentration in the edible plant parts. The highest iodine accumulation levels were observed in the first growing season: In butterhead lettuce and kohlrabi the desired iodine content [50-100 MUg I (100 g FM)(-1)] was obtained or exceeded at a fertilizer rate of 7.5 kg IO3 (-)-I ha(-1) without a significant yield reduction or impairment of the marketable quality. In contrast, supplying KI at the same rate resulted in a much lower iodine enrichment and clearly visible growth impairment. Soil applied iodine was phytoavailable only for a short period of time as indicated by a rapid decline of CaCl2-extractable iodine in the top soil. Consequently, long-term effects of a one-time iodine soil fertilization could not be observed. A comparison between the soil and the foliar fertilization revealed a better performance of iodine applied aerially to butterhead lettuce, which reached the desired iodine accumulation in edible plant parts at a fertilizer rate of 0.5 kg I(-)-I ha(-1). In contrast, the iodine content in the tuber of sprayed kohlrabi remained far below the targeted range. The results indicate that a sufficient spreading of iodine applied on the edible plant parts is crucial for the efficiency of the foliar approach and leafy vegetables are the more suitable target crops. The low iodine doses needed as well as the easy and inexpensive application may favor the implementation of foliar sprays as the preferred iodine biofortification strategy in practice. PMID- 26157446 TI - Loss of function of 1-FEH IIb has more impact on post-harvest inulin degradation in Cichorium intybus than copy number variation of its close paralog 1-FEH IIa. AB - Key Message: The loss of mini-exon 2 in the 1-FEH IIb glycosyl-hydrolase results in a putative non-functional allele. This loss of function has a strong impact on the susceptibility to post-harvest inulin depolymerization. Significant variation of copy number was identified in its close paralog 1-FEH IIa, but no quantitative effect of copy number on carbohydrates-related phenotypes was detected. Inulin polyfructan is the second most abundant storage carbohydrate in flowering plants. After harvest, it is depolymerized by fructan exohydrolases (FEHs) as an adaptive response to end-season cold temperatures. In chicory, the intensity of this depolymerization differs between cultivars but also between individuals within a cultivar. Regarding this phenotypic variability, we recently identified statistically significant associations between inulin degradation and genetic polymorphisms located in three FEHs. We present here new results of a systematic analysis of copy number variation (CNV) in five key members of the chicory (Cichorium intybus) GH32 multigenic family, including three FEH genes and the two inulin biosynthesis genes: 1-SST and 1-FFT. qPCR analysis identified a significant variability of relative copy number only in the 1-FEH IIa gene. However, this CNV had no quantitative effect. Instead, cloning of the full length gDNA of a close paralogous sequence (1-FEH IIb) identified a 1028 bp deletion in lines less susceptible to post-harvest inulin depolymerization. This region comprises a 9 bp mini-exon containing one of the three conserved residues of the active site. This results in a putative non-functional 1-FEH IIb allele and an observed lower inulin depolymerization. Extensive genotyping confirmed that the loss of mini-exon 2 in 1-FEH IIb and the previously identified 47 bp duplication located in the 3'UTR of 1-FEH IIa belong to a single haplotype, both being statistically associated with reduced susceptibility to post-harvest inulin depolymerization. Emergence of these haplotypes is discussed. PMID- 26157447 TI - Transcriptional profiles of Arabidopsis stomataless mutants reveal developmental and physiological features of life in the absence of stomata. AB - Loss of function of the positive stomata development regulators SPCH or MUTE in Arabidopsis thaliana renders stomataless plants; spch-3 and mute-3 mutants are extreme dwarfs, but produce cotyledons and tiny leaves, providing a system to interrogate plant life in the absence of stomata. To this end, we compared their cotyledon transcriptomes with that of wild-type plants. K-means clustering of differentially expressed genes generated four clusters: clusters 1 and 2 grouped genes commonly regulated in the mutants, while clusters 3 and 4 contained genes distinctively regulated in mute-3. Classification in functional categories and metabolic pathways of genes in clusters 1 and 2 suggested that both mutants had depressed secondary, nitrogen and sulfur metabolisms, while only a few photosynthesis-related genes were down-regulated. In situ quenching analysis of chlorophyll fluorescence revealed limited inhibition of photosynthesis. This and other fluorescence measurements matched the mutant transcriptomic features. Differential transcriptomes of both mutants were enriched in growth-related genes, including known stomata development regulators, which paralleled their epidermal phenotypes. Analysis of cluster 3 was not informative for developmental aspects of mute-3. Cluster 4 comprised genes differentially up-regulated in mute 3, 35% of which were direct targets for SPCH and may relate to the unique cell types of mute-3. A screen of T-DNA insertion lines in genes differentially expressed in the mutants identified a gene putatively involved in stomata development. A collection of lines for conditional overexpression of transcription factors differentially expressed in the mutants rendered distinct epidermal phenotypes, suggesting that these proteins may be novel stomatal development regulators. Thus, our transcriptome analysis represents a useful source of new genes for the study of stomata development and for characterizing physiology and growth in the absence of stomata. PMID- 26157448 TI - Flower abscission in Vitis vinifera L. triggered by gibberellic acid and shade discloses differences in the underlying metabolic pathways. AB - Understanding abscission is both a biological and an agronomic challenge. Flower abscission induced independently by shade and gibberellic acid (GAc) sprays was monitored in grapevine (Vitis vinifera L.) growing under a soilless greenhouse system during two seasonal growing conditions, in an early and late production cycle. Physiological and metabolic changes triggered by each of the two distinct stimuli were determined. Environmental conditions exerted a significant effect on fruit set as showed by the higher natural drop rate recorded in the late production cycle with respect to the early cycle. Shade and GAc treatments increased the percentage of flower drop compared to the control, and at a similar degree, during the late production cycle. The reduction of leaf gas exchanges under shade conditions was not observed in GAc treated vines. The metabolic profile assessed in samples collected during the late cycle differently affected primary and secondary metabolisms and showed that most of the treatment-resulting variations occurred in opposite trends in inflorescences unbalanced in either hormonal or energy deficit abscission-inducing signals. Particularly concerning carbohydrates metabolism, sucrose, glucose, tricarboxylic acid metabolites and intermediates of the raffinose family oligosaccharides pathway were lower in shaded and higher in GAc samples. Altered oxidative stress remediation mechanisms and indolacetic acid (IAA) concentration were identified as abscission signatures common to both stimuli. According to the global analysis performed, we report that grape flower abscission mechanisms triggered by GAc application and C starvation are not based on the same metabolic pathways. PMID- 26157449 TI - Effects of damping-off caused by Rhizoctonia solani anastomosis group 2-1 on roots of wheat and oil seed rape quantified using X-ray Computed Tomography and real-time PCR. AB - Rhizoctonia solani is a plant pathogenic fungus that causes significant establishment and yield losses to several important food crops globally. This is the first application of high resolution X-ray micro Computed Tomography (X-ray MUCT) and real-time PCR to study host-pathogen interactions in situ and elucidate the mechanism of Rhizoctonia damping-off disease over a 6-day period caused by R. solani, anastomosis group (AG) 2-1 in wheat (Triticum aestivum cv. Gallant) and oil seed rape (OSR, Brassica napus cv. Marinka). Temporal, non-destructive analysis of root system architectures was performed using RooTrak and validated by the destructive method of root washing. Disease was assessed visually and related to pathogen DNA quantification in soil using real-time PCR. R. solani AG2 1 at similar initial DNA concentrations in soil was capable of causing significant damage to the developing root systems of both wheat and OSR. Disease caused reductions in primary root number, root volume, root surface area, and convex hull which were affected less in the monocotyledonous host. Wheat was more tolerant to the pathogen, exhibited fewer symptoms and developed more complex root systems. In contrast, R. solani caused earlier damage and maceration of the taproot of the dicot, OSR. Disease severity was related to pathogen DNA accumulation in soil only for OSR, however, reductions in root traits were significantly associated with both disease and pathogen DNA. The method offers the first steps in advancing current understanding of soil-borne pathogen behavior in situ at the pore scale, which may lead to the development of mitigation measures to combat disease influence in the field. PMID- 26157450 TI - Tomato SlRbohB, a member of the NADPH oxidase family, is required for disease resistance against Botrytis cinerea and tolerance to drought stress. AB - NADPH oxidases (also known as respiratory burst oxidase homologs, Rbohs) are key enzymes that catalyze the generation of reactive oxygen species (ROS) in plants. In the present study, eight SlRboh genes were identified in tomato and their possible involvement in resistance to Botrytis cinerea and drought tolerance was examined. Expression of SlRbohs was induced by B. cinerea and Pseudomonas syringae pv. tomato but displayed distinct patterns. Virus-induced gene silencing based silencing of SlRbohB resulted in reduced resistance to B. cinerea but silencing of other SlRbohs did not affect the resistance. Compared to non silenced plants, the SlRbohB-silenced plants accumulated more ROS and displayed attenuated expression of defense genes after infection with B. cinerea. Silencing of SlRbohB also suppressed flg22-induced ROS burst and the expression of SlLrr22, a marker gene related to PAMP-triggered immunity (PTI). Transient expression of SlRbohB in Nicotiana benthamiana led to enhanced resistance to B. cinerea. Furthermore, silencing of SlRbohB resulted in decreased drought tolerance, accelerated water loss in leaves and the altered expression of drought-responsive genes. Our data demonstrate that SlRbohB positively regulates the resistance to B. cinerea, flg22-induced PTI, and drought tolerance in tomato. PMID- 26157451 TI - Burkholderia phytofirmans PsJN induces long-term metabolic and transcriptional changes involved in Arabidopsis thaliana salt tolerance. AB - Salinity is one of the major limitations for food production worldwide. Improvement of plant salt-stress tolerance using plant-growth promoting rhizobacteria (PGPR) has arisen as a promising strategy to help overcome this limitation. However, the molecular and biochemical mechanisms controlling PGPR/plant interactions under salt-stress remain unclear. The main objective of this study was to obtain new insights into the mechanisms underlying salt-stress tolerance enhancement in the salt-sensitive Arabidopsis thaliana Col-0 plants, when inoculated with the well-known PGPR strain Burkholderia phytofirmans PsJN. To tackle this, different life history traits, together with the spatiotemporal accumulation patterns for key metabolites and salt-stress related transcripts, were analyzed in inoculated plants under short and long-term salt-stress. Inoculated plants displayed faster recovery and increased tolerance after sustained salt-stress. PsJN treatment accelerated the accumulation of proline and transcription of genes related to abscisic acid signaling (Relative to Dessication, RD29A and RD29B), ROS scavenging (Ascorbate Peroxidase 2), and detoxification (Glyoxalase I 7), and down-regulated the expression of Lipoxygenase 2 (related to jasmonic acid biosynthesis). Among the general transcriptional effects of this bacterium, the expression pattern of important ion-homeostasis related genes was altered after short and long-term stress (Arabidopsis K(+) Transporter 1, High-Affinity K(+) Transporter 1, Sodium Hydrogen Exchanger 2, and Arabidopsis Salt Overly Sensitive 1). In all, the faster and stronger molecular changes induced by the inoculation suggest a PsJN priming effect, which may explain the observed tolerance after short-term and sustained salt-stress in plants. This study provides novel information about possible mechanisms involved in salt-stress tolerance induced by PGPR in plants, showing that certain changes are maintained over time. This opens up new venues to study these relevant biological associations, as well as new approaches to a better understanding of the spatiotemporal mechanisms involved in stress tolerance in plants. PMID- 26157452 TI - Digital gene expression analysis of male and female bud transition in Metasequoia reveals high activity of MADS-box transcription factors and hormone-mediated sugar pathways. AB - Metasequoia glyptostroboides is a famous redwood tree of ecological and economic importance, and requires more than 20 years of juvenile-to-adult transition before producing female and male cones. Previously, we induced reproductive buds using a hormone solution in juvenile Metasequoia trees as young as 5-to-7 years old. In the current study, hormone-treated shoots found in female and male buds were used to identify candidate genes involved in reproductive bud transition in Metasequoia. Samples from hormone-treated cone reproductive shoots and naturally occurring non-cone setting shoots were analyzed using 24 digital gene expression (DGE) tag profiles using Illumina, generating a total of 69,520 putative transcripts. Next, 32 differentially and specifically expressed transcripts were determined using quantitative real-time polymerase chain reaction, including the upregulation of MADS-box transcription factors involved in male bud transition and flowering time control proteins involved in female bud transition. These differentially expressed transcripts were associated with 243 KEGG pathways. Among the significantly changed pathways, sugar pathways were mediated by hormone signals during the vegetative-to-reproductive phase transition, including glycolysis/gluconeogenesis and sucrose and starch metabolism pathways. Key enzymes were identified in these pathways, including alcohol dehydrogenase (NAD) and glutathione dehydrogenase for the glycolysis/gluconeogenesis pathway, and glucanphosphorylase for sucrose and starch metabolism pathways. Our results increase our understanding of the reproductive bud transition in gymnosperms. In addition, these studies on hormone-mediated sugar pathways increase our understanding of the relationship between sugar and hormone signaling during female and male bud initiation in Metasequoia. PMID- 26157453 TI - Seed shattering: from models to crops. AB - Seed shattering (or pod dehiscence, or fruit shedding) is essential for the propagation of their offspring in wild plants but is a major cause of yield loss in crops. In the dicot model species, Arabidopsis thaliana, pod dehiscence necessitates a development of the abscission zones along the pod valve margins. In monocots, such as cereals, an abscission layer in the pedicle is required for the seed shattering process. In the past decade, great advances have been made in characterizing the genetic contributors that are involved in the complex regulatory network in the establishment of abscission cell identity. We summarize the recent burgeoning progress in the field of genetic regulation of pod dehiscence and fruit shedding, focusing mainly on the model species A. thaliana with its close relatives and the fleshy fruit species tomato, as well as the genetic basis responsible for the parallel loss of seed shattering in domesticated crops. This review shows how these individual genes are co-opted in the developmental process of the tissues that guarantee seed shattering. Research into the genetic mechanism underlying seed shattering provides a premier prerequisite for the future breeding program for harvest in crops. PMID- 26157454 TI - Future opportunities and trends for e-infrastructures and life sciences: going beyond the grid to enable life science data analysis. AB - With the increasingly rapid growth of data in life sciences we are witnessing a major transition in the way research is conducted, from hypothesis-driven studies to data-driven simulations of whole systems. Such approaches necessitate the use of large-scale computational resources and e-infrastructures, such as the European Grid Infrastructure (EGI). EGI, one of key the enablers of the digital European Research Area, is a federation of resource providers set up to deliver sustainable, integrated and secure computing services to European researchers and their international partners. Here we aim to provide the state of the art of Grid/Cloud computing in EU research as viewed from within the field of life sciences, focusing on key infrastructures and projects within the life sciences community. Rather than focusing purely on the technical aspects underlying the currently provided solutions, we outline the design aspects and key characteristics that can be identified across major research approaches. Overall, we aim to provide significant insights into the road ahead by establishing ever strengthening connections between EGI as a whole and the life sciences community. PMID- 26157456 TI - Using parental phenotypes in case-parent studies. AB - In studies of case-parent triads, information is often collected about history of the condition in the parents, but typically parental phenotypes are ignored. Including that information in analyses may increase power to detect genetic association for autosomal variants. Our proposed approach uses parental phenotypes to assess association independently of the usual case-parent-based association test, enabling cross-generational internal replication for findings based on offspring and their parents. Our model for parental phenotypes also resists bias due to population stratification. We combine the information from the two generations into a single coherent model that can exploit approximate equality of parental and offspring relative risks to improve power and can also test that equality. We call the resulting procedure the Parent-phenotype Informed Likelihood Ratio Test (PPI-LRT). When some parental genotypes are missing, one can use the expectation-maximization algorithm to fit the combined model. We also develop a second composite test (PPI-CT) based on a linear combination of the parent-phenotype-based test statistic and that from the traditional log-linear, transmission-based test. We evaluate the proposed methods through non-centrality parameter calculations and simulation studies and compare them to the previously proposed approaches, parenTDT and combTDT. We show that incorporation of parental phenotype data often improves statistical power. As illustration, we apply our method to a study of young-onset breast cancer and find that it improved precision for SNPs in FGFR2 and that estimated relative risks based on triads are closely replicated using the parental data. PMID- 26157455 TI - From next-generation sequencing to systematic modeling of the gut microbiome. AB - Changes in the human gut microbiome are associated with altered human metabolism and health, yet the mechanisms of interactions between microbial species and human metabolism have not been clearly elucidated. Next-generation sequencing has revolutionized the human gut microbiome research, but most current applications concentrate on studying the microbial diversity of communities and have at best provided associations between specific gut bacteria and human health. However, little is known about the inner metabolic mechanisms in the gut ecosystem. Here we review recent progress in modeling the metabolic interactions of gut microbiome, with special focus on the utilization of metabolic modeling to infer host-microbe interactions and microbial species interactions. The systematic modeling of metabolic interactions could provide a predictive understanding of gut microbiome, and pave the way to synthetic microbiota design and personalized microbiome medicine and healthcare. Finally, we discuss the integration of metabolic modeling and gut microbiome engineering, which offer a new way to explore metabolic interactions across members of the gut microbiota. PMID- 26157457 TI - Poor Sleep Quality in Patients after Coronary Artery Bypass Graft Surgery: An Intervention Study Using the PRECEDE-PROCEED Model. AB - BACKGROUND: Poor sleep quality (SQ) is common among patients after coronary artery bypass graft surgery (CABG). This study attempted to determine the status of SQ following an intervention based on the PRECEDE-PROCEED model in patients with poor SQ after CABG. METHODS: This study was a randomized clinical trial. The study sample, including 100 patients referred to the Cardiac Rehabilitation Clinic of Tehran Heart Center, was assigned either to the intervention (recipient of exercise and lifestyle training plus designed intervention based on the PRECEDE-PROCEED model) or to the control group (recipient of exercise and lifestyle training). Eight training sessions over 8 weeks were conducted for the intervention group. Predisposing, enabling, and reinforcing factors as well as social support and SQ were measured in the intervention group before and one month after the intervention and compared to those in the control group at the same time points. RESULTS: The mean age of the patients in the intervention (24% women) and control (24% women) groups was 59.3 +/- 7.3 and 59.5 +/- 9.3 years, respectively. The results showed that the mean scores of SQ (p value < 0.001), knowledge (p value < 0.001), beliefs (p value < 0.001), sleep self-efficacy (p value < 0.001), enabling factors (p value < 0.001), reinforcing factors (p value < 0.001), and social support (p value < 0.001) were significantly different between the intervention and control groups after the intervention. CONCLUSION: Adding an intervention based on the PRECEDE-PROCEED model to the cardiac rehabilitation program may further improve the SQ of patients. PMID- 26157458 TI - Survey of Sleep Status and its Related Factors among Hospitalized Patients with Heart Failure. AB - BACKGROUND: Sleep disorders among heart failure (HF) patients negatively influence the quality of life. Awareness of sleep disturbances, as one of the disturbing factors of the quality of life among HF patients, and its related factors would help health care staff to provide more comprehensive care. Hence, this study was conducted to determine the quality of sleep and its related factors in hospitalized patients with HF. METHODS: This cross-sectional survey study was conducted on 240 patients with HF hospitalized in one of the health centers of Guilan University of Medical Sciences between July and December 2013. Samples were selected by convenience sampling. The Pittsburgh Sleep Quality Index and a researcher-designed questionnaire on sleep disturbing factors were the instruments of this study. The correlation and relationship between sleep quality and variables related to personal, environmental, and disease factors were assessed. RESULTS: The majority of the samples (91.2%) had a poor sleep quality. A significant positive correlation was found between sleep quality and age (r = 0.322; p value < 0.001), body mass index (r = 0.212; p value < 0.001), number of comorbidities (r = 0.205; p value = 0.001), number of hospitalizations (r = 0.202; p value < 0.001), number of drugs consumed (r = 0.178; p value = 0.003), and length of stay in hospital (r = 0.149; p value = 0.011). Also, significant differences were seen between sleep quality and sex (p value = 0.014), smoking (p value = 0.038), educational level (p value = 0. 047), and hospital noise (p value = 0. 004). CONCLUSION: Age, sex, educational level, smoking, and obesity were the most significant factors affecting the sleep quality in our HF patients. PMID- 26157459 TI - Relationship between Body Mass Index and Outcome of Elective Percutaneous Coronary Intervention. AB - BACKGROUND: Studies have shown controversial effects of obesity on major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI). We sought to investigate the impact of the body mass index (BMI) on the mid-term outcome following successful PCI. METHODS: Between March 2006 and August 2008, 3948 patients underwent successful elective PCI in Tehran Heart Center, Tehran, Iran, and were retrospectively included in this study. Patients who underwent PCI on the same day as the occurrence of myocardial infarction were excluded. The demographic, procedural, in-hospital, and follow-up information of these patients was extracted from the PCI Data Registry of our institution. The patients were divided into three groups: normal weight (No. 1058, BMI < 25 kg/m(2) age = 58 +/- 10 years); overweight (No. 1867, 25 <= BMI < 30 kg/m(2), age = 57 +/- 10 years); and obese (No. 1023, BMI >= 30 kg/m(2), age = 56 +/- 10 years). MACE included death, myocardial infarction, target vessel revascularization, and target lesion revascularization. RESULTS: Compared with the other patients, the obese individuals were significantly younger and more frequently female, had a higher ejection fraction, and more frequently presented with hypertension, diabetes, and hyperlipidemia. There was no association between the BMI and the angiographic and procedural findings in the univariate analysis. While no difference was found in the rate of in-hospital death between the groups, the number of the obese patients undergoing emergent cardiac surgery was marginally different in the univariate analysis (p value = 0.06). At 9 months' follow-up, MACE had occurred in 92 (2.3%) patients and cardiac mortality was 9 (0.2%). After adjustments for confounders, no significant difference was observed in terms of MACE between the BMI groups. CONCLUSION: The BMI had no significant effect on the rate of MACE at 9 months' follow-up in our study population. Interventionists' recommendations for patients undergoing PCI should, therefore, not be significantly influenced by the BMI status. PMID- 26157460 TI - Cross-Country Differences in the Additive Effects of Socioeconomics, Health Behaviors and Medical Comorbidities on Disability among Older Adults with Heart Disease. AB - BACKGROUND: Patients with heart disease experience limited activities of daily living (ADL). This is a cross-country comparison of the additive effects of Socioeconomics, health behaviors, and the number of medical comorbidities on disability among patients with heart disease. METHODS: The current study used a cross-sectional design. Data came from the Research on Early Life and Aging Trends and Effects (RELATE). The current analysis utilized data on elderly individuals (age >=60 y) from 13 countries. The outcome was any ADL limitation (i.e. bathing, dressing, using toilet, transferring, lifting heavy things, shopping, and eating meals). Socioeconomics (i.e. age, gender, education, and income), health behaviors (i.e. exercise, smoking, and drinking), and number of chronic medical conditions (i.e. hypertension, respiratory, arthritis, stroke, and diabetes) were entered into country-specific logistic regressions, considering at least one limitation in ADL as the main outcome. RESULTS: Number of comorbid medical conditions and age were positively associated with disability in 85% of the countries. Physical activity and drinking were linked to disability in 54%and 31% of countries, respectively. Higher education and income were associated with lower disability in 31% and 23% of the countries, respectively. Female gender was associated with higher disability only in 15% of the countries. Smoking was not associated with disability, while the effects of socioeconomics, drinking, exercise, and medical comorbidities were controlled. CONCLUSION: Determinants of disability depend on the country; accordingly, locally designed health promotion interventions may be superior to the universal interventions for patients with heart disease. Medical comorbidities, however, should be universally diagnosed and treated. PMID- 26157461 TI - Introducing the Tehran Heart Center's Premature Coronary Atherosclerosis Cohort: THC-PAC Study. AB - BACKGROUND: Data on premature coronary artery disease (CAD) are scarce. The Tehran Heart Center's Premature Coronary Atherosclerosis Cohort Study (THC-PAC) is the first study of its kind in the Middle East to assess major adverse cardiac events (MACE) in young CAD patients. METHODS: The cohort consists of CAD patients, males <= 45 years old and females <= 55 years old. The participants are residents of Tehran or its suburbs and underwent coronary angiography between June 2004 and July 2011. A 10-year follow-up, via either clinical visits or telephone calls at least once a year, was commenced in August 2012. The end point is considered MACE, encompassing death, myocardial infarction, stroke, new coronary involvement, percutaneous coronary intervention, and coronary artery bypass grafting. RESULTS: The cohort comprises 1232 eligible patients (613 [49.8%] males) at a mean age of 45.1 years (SD = 5.8). High frequencies of conventional risk factors, including hyperlipidemia (884 [71.8%]), hypertension (575 [46.7%]), positive family history (539 [43.8%]), cigarette smoking (479 [38.8%]), and diabetes mellitus (390 [31.7%]), were seen in the participants. The mean body mass index (BMI) of the enrolled patients was high (29.2 +/- 4.8 kg/m(2)), and 532 (43.3%) and 440 (35.8%) of them were overweight and obese, respectively. The females' BMI was higher (30.4 +/- 5.3 vs. 28.0 +/- 3.9 kg/m2; P < 0.001) and they had a greater mean abdominal circumference (99.9 +/- 13.5 vs. 98.1 +/- 9.3 cm; P = 0.035). Between August 2012 and August 2013, follow-up was successful in 1173 (95.2%) patients (median follow-up duration = 55.3 months, 95%CI: 53.5-57.0 months). CONCLUSION: Our younger patients with CAD had a high frequency of risk factors compared to the same-age general population and all-age CAD patients, which may predispose them to higher incidence of recurrent MACE. PMID- 26157462 TI - Beating Heart Mitral Valve Replacement Surgery without Aortic Cross-Clamping via Right Thoracotomy in a Patient with Compromised Left Ventricular Functions. AB - Global myocardial ischemia and ischemia-reperfusion injury are potential adverse events related with cardioplegic arrest. Beating heart surgery has avoided such complications and adapted to valve surgery following successful results published on myocardial revascularization. Difficulty in weaning from cardiopulmonary bypass may be lessened by using on-pump beating heart surgery for mitral valve interventions. Here we describe a 64-year-old male patient with severe mitral regurgitation and dilated cardiomyopathy. Beating heart mitral valve replacement surgery was performed without aortic cross-clamping through a right thoracotomy approach. We believe that, particularly in patients with poor left ventricular functions, beating heart mitral valve surgery may be advantageous. PMID- 26157463 TI - Right Ventricular Thrombus in a 36-Year-Old Man with Factor V Leiden. AB - Factor V Leiden deficiency is the most common hereditary hypercoagulable disease in the United States and involves 5% of the Caucasian population. Up to 30% of patients who present with deep vein thrombosis (DVT) or pulmonary thromboembolism present with this condition. This is a case report of a 36-year-old man who experienced one episode of DVT within the previous year and was admitted to our hospital due to productive coughs and hemoptysis. Paraclinical studies demonstrated a right ventricular thrombus. Additional investigation was done to find the underlying cause. Laboratory tests were positive for Factor V Leiden mutation. Other factors for hypercoagulability states were normal. Given that Factor V Leiden mutation is a life-threatening condition with a relatively high prevalence and considering its thrombogenesis, screening tests are necessary in young patients without obvious reasons for recurrent thrombus formation. It seems that medical noninvasive treatments can be an alternative therapy to surgery when a ventricular thrombus is suspected in these patients. PMID- 26157464 TI - Severe Tricuspid Regurgitation Diagnosed 13 Years after a Car Accident: A Case Report. AB - Blunt chest traumas mostly occur due to car accidents and can cause many cardiac complications such as septal rupture, free-wall rupture, coronary artery dissection or thrombosis, heart failure, arrhythmias, and chordae and papillary muscle rupture. One of the most serious complication is tricuspid regurgitation (TR), which can be simply diagnosed by physical examination and confirmed by echocardiography. We describe a 48-year-old female patient, diagnosed with severe TR 13 years after a blunt chest trauma due to a car accident. TR was diagnosed with transthoracic echocardiography and three dimensional transthoracic echocardiography had defined the exact pathology of the tricuspid valve. The patient underwent successful surgery with bioprosthetic valve implantation and was discharged at 6th postoperative day without any complication. The patient had no problem according to the follow-up one month and six months after operation. PMID- 26157465 TI - Huge Left Atrium Accompanied by Normally Functioning Prosthetic Valve. AB - Giant left atria are defined as those measuring larger than 8 cm and are typically found in patients who have rheumatic mitral valve disease with severe regurgitation. Enlargement of the left atrium may create compression of the surrounding structures such as the esophagus, pulmonary veins, respiratory tract, lung, inferior vena cava, recurrent laryngeal nerve, and thoracic vertebrae and lead to dysphagia, respiratory dysfunction, peripheral edema, hoarse voice, or back pain. However, a huge left atrium is usually associated with rheumatic mitral valve disease but is very rare in a normally functioning prosthetic mitral valve, as was the case in our patient. A 46-year-old woman with a past medical history of mitral valve replacement and chronic atrial fibrillation was admitted to our hospital with a chief complaint of cough and shortness of breath, worsened in the last month. Physical examination showed elevated jugular venous pressure, respiratory distress, cardiac cachexia, heart failure, hepatomegaly, and severe edema in the legs. Chest radiography revealed an inconceivably huge cardiac sell out. Transthoracic echocardiography demonstrated a huge left atrium, associated with thrombosis, and normal function of the prosthetic mitral valve. Cardiac surgery with left atrial exploration for the extraction of the huge thrombosis and De Vega annuloplasty for tricuspid regurgitation were carried out. The postoperative course was eventful due to right ventricular failure and low cardiac output syndrome; and after two days, the patient expired with multiple organ failure. Thorough literature review showed that our case was the largest left atrium (20 * 22 cm) reported thus far in adults with a normal prosthetic mitral valve function. PMID- 26157466 TI - A Diagnostic Analysis of Erroneous Language in Iranian Medical Specialists' Research Papers. AB - BACKGROUND: As English has increasingly become the lingua franca in science and international journals require native-like academic writing standards from nonnative researchers, there is more pressure on nonnative scholars to write their research articles more accurately and appropriately in English. This study was conducted to determine the most-occurring language-related errors which Iranian medical authors/researchers commit while trying to have their research published in international English journals. Also, this article seeks to provide useful guidelines to reduce such linguistic mistakes. METHODS: The present study investigated the most common language-related errors in Iranian medical specialists' research articles. To this end, the first drafts of 60 published research articles in medical sciences were cross-checked against their peer reviewed published versions in order to identify the most frequent non-target language forms which received discoursal, lexical, grammatical, and mechanical revisions by peer editors. RESULTS: The findings revealed that the editors had surprisingly dealt with discoursal errors more than any other linguistic aspects of these research articles. This was followed by lexical replacements. In third place were grammatical improvements, where erroneous structures mostly related to tenses, usage of articles and prepositions, and agreement between verbs and nouns were treated. The least common revisions were on the mechanics of academic writing, consisting of hyphenating, spelling, case lettering, spacing, and spacing with commas. CONCLUSION: Although most of the Iranian medical authors/researchers enjoyed a good level of proficiency in English, their manuscripts required discoursal, lexical, grammatical, and mechanical revisions before publication in credited international journals. PMID- 26157467 TI - Loss of Guide Wire: A Rare Complication of Intra-Aortic Balloon Pump Insertion. AB - At the final stages of a coronary artery bypass graft operation on a 64-year-old man, an experienced physician attempted to insert an intra-aortic balloon pump into the femoral artery via the Seldinger technique. However, while the balloon pump was being passed over the guide wire, the latter was completely lost. The guide wire should be held at the tip at all times to prevent passage into the vessel. Strict adherence to this rule will prevent guide-wire loss, which is, albeit rare and completely avoidable, a potentially life-threatening complication of central vein or artery catheterization, with reported fatality rates of up to 20% when the whole wire is lost. The literature contains several reports on guide wire loss during central venous, arterial, and hemodialysis catheterization, but we report for the first time the loss of a guide wire as a rare complication of intra-aortic balloon pump insertion. PMID- 26157468 TI - The combined molecular adjuvant CASAC enhances the CD8+ T cell response to a tumor-associated self-antigen in aged, immunosenescent mice. AB - BACKGROUND: Ineffective induction of T cell mediated immunity in older individuals remains a persistent challenge for vaccine development. Thus, there is a need for more efficient and sophisticated adjuvants that will complement novel vaccine strategies for the elderly. To this end, we have investigated a previously optimized, combined molecular adjuvant, CASAC (Combined Adjuvant for Synergistic Activation of Cellular immunity), incorporating two complementary Toll-like receptor agonists, CpG and polyI:C, a class-II epitope, and interferon (IFN)-gamma in aged mice. FINDINGS: In aged mice with typical features of immunosenescence, antigen specific CD8+ T cell responses were stimulated after serial vaccinations with CASAC or Complete/Incomplete Freund's Adjuvant (CFA/IFA) and a class I epitope, deriving either from ovalbumin (SIINFEKL, SIL) or the melanoma-associated self-antigen, tyrosinase-related protein-2 (SVYDFFVWL, SVL). Pentamer analysis revealed that aged, CASAC/SIL-vaccinated animals had substantially higher frequencies of H-2K(b)/SIL-specific CD8+ T cells compared to the CFA/IFA-vaccinated groups. Similarly, higher frequencies of H-2K(b)/SVL pentamer+ and IFN-gamma+ CD8+ T cells were detected in the aged, CASAC + SVL vaccinated mice than in their CFA/IFA-vaccinated counterparts. In both antigen settings, CASAC promoted significantly better functional CD8+ T cell activity. CONCLUSION: These studies demonstrate that functional CD8+ T cells, specific for both foreign and tumour-associated self-antigens, can be effectively induced in aged immunosenescent mice using the novel multi-factorial adjuvant CASAC. PMID- 26157469 TI - Less functional variants of TLR-1/-6/-10 genes are associated with age. AB - BACKGROUND: Determining the prerequisites for healthy aging is a major task in the modern world characterized by a longer lifespan of the individuals. Besides lifestyle and environmental influences genetic factors are involved as shown by several genome-wide association studies. Older individuals are known to have an impaired immune response, a condition recently termed "inflamm-aging". We hypothesize that the induction of this condition in the elderly is influenced by the sensitivity of the innate immune system. Therefore, we investigated genetic variants of the Toll-like receptor (TLR) family, one of the major family of innate immune receptors, for association with age in two cohorts of healthy, disease-free subjects. RESULTS: According to sex we found a positive association of loss-of-function variants of TLR-1 and -6 with healthy aging with odds ratios of 1.54 in males for TLR-6 (249 S/S), and 1.41, 1.66, and 1.64 in females for TLR 1 prom., TLR-1 (248 S/S), and TLR-1 (602 S/S), respectively. Thus, the presence of these variants increases the probability of achieving healthy old age and indicates that a reduced TLR activity may be beneficial in the elderly. CONCLUSIONS: This is the first report showing an association of TLR variants with age. While a loss of function of an important immune receptor may be a risk factor for acute infections as has been shown previously, in the setting of healthy ageing it appears to be protective, which may relate to "inflamm-aging". These first results should be reproduced in larger trials to confirm this hypothesis. PMID- 26157470 TI - Sensorial pedagogies, hungry fat cells and the limits of nutritional health education. AB - This article examines the way the category of 'the sensorial' is mobilised across obesity research and care practices for overweight persons in France. The 'natural' body is understood to have developed mechanisms that motivate eaters to seek out energy-dense foods, a hardwiring that is maladaptive in today's plethoric food environment. The article analyses the feedback models mobilised in scientific literature on the neuroendocrine processes regulating appetite. The analysis of how 'the sensorial' is studied and used to treat patients provides a vantage point onto the ways foods and bodies transform each other. Recent findings show that fat cells influence metabolism by secreting hormones, revealing that eaters are affected by the materiality of the foods they ingest. 'The sensorial' functions as a regulator in the feedback mechanisms where social norms regulating foodscapes become enfolded in the molecular processes that control appetite regulation. The article traces the work that the category of 'the sensorial' does as it flows through the loops and feedbacks between scientific evidence, policy and care. It examines the way pleasure and the sensations of eaters are increasingly foregrounded in French nutritional health promotion strategies in a context where informing eaters is increasingly deemed ineffective. PMID- 26157471 TI - Materiality matters: Blurred boundaries and the domestication of functional foods. AB - Previous scholarship on novel foods, including functional foods, has suggested that they are difficult to categorise for both regulators and users. It is argued that they blur the boundary between 'food' and 'drug' and that uncertainties about the products create 'experimental' or 'restless' approaches to consumption. We investigate these uncertainties drawing on data about the use of functional foods containing phytosterols, which are licensed for sale in the EU for people wishing to reduce their cholesterol. We start from an interest in the products as material objects and their incorporation into everyday practices. We consider the scripts encoded in the physical form of the products through their regulation, production and packaging and find that these scripts shape but do not determine their use. The domestication of phytosterols involves bundling the products together with other objects (pills, supplements, foodstuffs). Considering their incorporation into different systems of objects offers new understandings of the products as foods or drugs. In their accounts of their practices, consumers appear to be relatively untroubled by uncertainties about the character of the products. We conclude that attending to materials and practices offers a productive way to open up and interrogate the idea of categorical uncertainties surrounding new food products. PMID- 26157472 TI - A pin-fasten grafting method provides a non-sterile and highly efficient method for grafting Arabidopsis at diverse developmental stages. AB - BACKGROUND: Higher plants have evolved sophisticated communication systems to integrate environmental stimuli into their developmental programs. Grafting provides a powerful technique to examine transportation and systemic effects of mobile molecules. In Arabidopsis, many grafting approaches have been developed to investigate systemic molecules. However, these methods are usually limited to specific developmental stages or require sterilized conditions. To broaden the application of grafting for examining systemic signals at diverse developmental stages, we developed an Arabidopsis pin-fasten grafting method with insect pins used to assemble stocks and scions. RESULTS: We report the step-by-step protocol of Arabidopsis pin-fasten grafting. Arabidopsis wild-type or gl1-1 plants were grown under long- or short-day conditions. Insect pins were inserted into gl1-1 scions at different developmental stages for grafting onto epicotyls or hypocotyls of stocks. Successfully grafted scions with newly developed glabrous leaves were observed at 14 days after grafting. Further longitudinal sections of the graft union showed well-connected vascular tissues between grafted plants. Use of fluorescent phloem-limited dye carboxyfluorescein diacetate in grafted plants demonstrated a symplastic connection established at 6 days after grafting and almost fully developed at 8 days. CONCLUSIONS: Our method provides a simple and robust approach to grafting Arabidopsis at different developmental stages. Sterilized conditions are not required, which greatly improves the success of grafting and plant growth. PMID- 26157473 TI - An online peak extraction algorithm for ion mobility spectrometry data. AB - Ion mobility (IM) spectrometry (IMS), coupled with multi-capillary columns (MCCs), has been gaining importance for biotechnological and medical applications because of its ability to detect and quantify volatile organic compounds (VOC) at low concentrations in the air or in exhaled breath at ambient pressure and temperature. Ongoing miniaturization of spectrometers creates the need for reliable data analysis on-the-fly in small embedded low-power devices. We present the first fully automated online peak extraction method for MCC/IMS measurements consisting of several thousand individual spectra. Each individual spectrum is processed as it arrives, removing the need to store the measurement before starting the analysis, as is currently the state of the art. Thus the analysis device can be an inexpensive low-power system such as the Raspberry Pi. The key idea is to extract one-dimensional peak models (with four parameters) from each spectrum and then merge these into peak chains and finally two-dimensional peak models. We describe the different algorithmic steps in detail and evaluate the online method against state-of-the-art peak extraction methods. PMID- 26157474 TI - Inferring interaction type in gene regulatory networks using co-expression data. AB - BACKGROUND: Knowledge of interaction types in biological networks is important for understanding the functional organization of the cell. Currently information based approaches are widely used for inferring gene regulatory interactions from genomics data, such as gene expression profiles; however, these approaches do not provide evidence about the regulation type (positive or negative sign) of the interaction. RESULTS: This paper describes a novel algorithm, "Signing of Regulatory Networks" (SIREN), which can infer the regulatory type of interactions in a known gene regulatory network (GRN) given corresponding genome-wide gene expression data. To assess our new approach, we applied it to three different benchmark gene regulatory networks, including Escherichia coli, prostate cancer, and an in silico constructed network. Our new method has approximately 68, 70, and 100 percent accuracy, respectively, for these networks. To showcase the utility of SIREN algorithm, we used it to predict previously unknown regulation types for 454 interactions related to the prostate cancer GRN. CONCLUSIONS: SIREN is an efficient algorithm with low computational complexity; hence, it is applicable to large biological networks. It can serve as a complementary approach for a wide range of network reconstruction methods that do not provide information about the interaction type. PMID- 26157475 TI - Maxillofacial and neck trauma: a damage control approach. AB - Severe maxillofacial and neck trauma exposes patients to life threatening complications such as airway compromise and hemorrhagic shock. These conditions require rapid actions (diagnosis and management) and a strong interplay between surgeons and anesthesiologists. Effective airway management often makes the difference between life and death in severe maxillofacial and neck trauma and takes initial precedence over all other clinical considerations. Damage control strategies focus on physiological and biochemical stabilization prior to the comprehensive anatomical and functional repair of all injuries. Damage control surgery (DCS) can be defined as the rapid initial control of hemorrhage and contamination, temporary wound closure, resuscitation to normal physiology in the intensive care unit (ICU) and subsequent reexploration and definitive repair following restoration of normal physiology. Damage control resuscitation (DCR) consists mainly of hypotensive (permissive hypotension) and hemostatic (minimal use of crystalloid fluids and utilization of blood and blood products) resuscitation. Both strategies should be administered simultaneously in all of these patients. PMID- 26157476 TI - Viral non-coding RNA inhibits HNF4alpha expression in HCV associated hepatocellular carcinoma. AB - BACKGROUND: Hepatitis C virus (HCV) infection is an established cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC); however, it is unclear if the virus plays a direct role in the development of HCC. Hepatocyte nuclear factor 4alpha (HNF4alpha) is critical determinant of epithelial architecture and hepatic development; depletion of HNF4alpha is correlated with oncogenic transformation. We explored the viral role in the inhibition of HNF4alpha expression, and consequent induction of tumor-promoting genes in HCV infection associated HCC. METHODS: Western blot analysis was used to monitor the changes in expression levels of oncogenic proteins in liver tissues from HCV-infected humanized mice. The mechanism of HNF4alpha depletion was studied in HCV-infected human hepatocyte cultures in vitro. Targeting of HNF4alpha expression by viral non-coding RNA was examined by inhibition of Luciferase HNF4alpha 3'-UTR reporter. Modulation of invasive properties of HCV-infected cells was examined by Matrigel cell migration assay. RESULTS: Results show inhibition of HNF4alpha expression by targeting of HNF4alpha 3'-UTR by HCV-derived small non-coding RNA, vmr11. Vmr11 enhances the invasive properties of HCV-infected cells. Loss of HNF4alpha in HCV-infected liver tumors of humanized mice correlates with the induction of epithelial to mesenchymal transition (EMT) genes. CONCLUSIONS: We show depletion of HNF4alpha in liver tumors of HCV-infected humanized mice by HCV derived small non-coding RNA (vmr11) and resultant induction of EMT genes, which are critical determinants of tumor progression. These results suggest a direct viral role in the development of hepatocellular carcinoma. PMID- 26157477 TI - Nonsuicidal self-injury in sexual minority college students: a test of theoretical integration. AB - BACKGROUND: Individuals identifying as a sexual minority report engaging in nonsuicidal self-injury (NSSI) at substantially higher rates compared to their heterosexual peers. Given that NSSI is a known risk factor for suicide, it is important to understand the processes unique to being a sexual minority that increases risk for NSSI so that adequate prevention efforts can be established. The current study integrated Minority Stress Theory and the Interpersonal Theory of Suicide to test a model of NSSI and suicide risk. METHODS: A total of 137 college students who identified as a sexual minority completed an anonymous on line study assessing NSSI, suicidal thoughts/behaviors, and constructs of the minority stress and interpersonal theories. Two linear regressions using bootstrapping analyses were conducted to test our hypotheses. RESULTS: Minority stress was directly associated with NSSI and via perceived burdensomeness, explaining 27 % of the variance. NSSI was associated with increased risk for suicide thoughts/behaviors directly, and through acquired capability, explaining 45 % of the variance. CONCLUSIONS: These findings provide evidence that unique stressors individuals face as a result of their sexual minority status increases risk for self-harm by influencing cognitive and emotional processes such as burdensomeness and acquired capability. Implications for prevention, intervention, and future research are briefly discussed. PMID- 26157478 TI - Parenting behavior in families of female adolescents with nonsuicidal self-injury in comparison to a clinical and a nonclinical control group. AB - BACKGROUND: Nonsuicidal self-injury (NSSI) is often accompanied by dysfunctional familial relationships. Problems within the family are also frequent triggers for NSSI. METHODS: The current study investigated the parenting behavior in families of 45 female adolescents with NSSI disorder, 27 adolescents with other mental disorders (clinical controls, CCs), and 44 adolescents without mental disorders (nonclinical controls, NCs). The adolescents and their parents (92 mothers, 24 fathers) were surveyed using self-report measures. The parenting dimensions warmth and support, psychological control, and behavioral control (demands, rules, and discipline), as well as parental psychopathology and parental satisfaction were assessed. RESULTS: Adolescents with NSSI disorder reported significantly less maternal warmth and support than NCs (d = .64); this group difference was not evident in mothers' reports. No group differences emerged regarding adolescent-reported paternal parenting behavior. Mothers of adolescents with NSSI reported higher depression, anxiety, and stress scores than mothers in the NC group and less parental satisfaction than mothers in both control groups (CC and NC). CONCLUSIONS: Given the association between NSSI, low levels of adolescent-reported maternal warmth and support and low levels of mother-reported parental satisfaction, clinical interventions for adolescents with NSSI should focus on improving family communication and interaction. PMID- 26157479 TI - Characteristics of nonsuicidal self-injury associated with suicidal ideation: evidence from a clinical sample of youth. AB - BACKGROUND: Nonsuicidal self-injury (NSSI) and suicidal ideation (SI) are both distressing and quite common, particularly in youth. Given the relationship between these two phenomena, it is crucial to learn how we can use information about NSSI to understand who is at greatest risk of suicidal thoughts. In this study, we investigated how characteristics of nonsuicidal self-injury related to SI among treatment-seeking adolescents and young adults. METHODS: Data were collected during routine program evaluation for a self-injury treatment program. Correlations between recent SI and NSSI characteristics were calculated for adolescent and young adult patients (N = 1502). RESULTS: Low severity methods of NSSI (e.g. banging) were more strongly associated with SI than high severity methods (e.g. breaking bones). SI was associated with intrapersonal (automatic) NSSI functions. SI was associated with some indices of NSSI severity, such as number of methods and urge for NSSI, but not with others, such as age of onset. CONCLUSIONS: This study provides a valuable opportunity to expand our knowledge of suicide risk factors beyond those that may apply broadly to self-injurers and to non-injurers (e.g., depression, substance use) to NSSI-related factors that might be specifically predictive of suicidal thoughts among self-injurers. Findings inform clinical risk assessment of self-injurious youth, a population at high risk of suicidal thoughts and behaviors, and provide further insight into the complex NSSI/suicide relationship. PMID- 26157480 TI - Non-suicidal self-injury maintenance and cessation among adolescents: a one-year longitudinal investigation of the role of objectified body consciousness, depression and emotion dysregulation. AB - Using the objectification theory, scholars have theorized the sense of detachment and disregard for the body that results from continued body objectification are believed to put a person at greater risk for non-suicidal self-injury (NSSI), due to a lack of emotional investment in the body. The goal of the current study was to longitudinally investigate the association between body objectification and NSSI among an early adolescent sample. The overall sample consisted of 120 participants (56 % female) who ranged in age from 11 to 13 years of age (M = 12.34, SD = .48). Participants were followed over the course of a 12-month period, and classified into three groups of interest; adolescents who reported maintaining NSSI behaviour over the course of a year (NSSI Maintain group, n = 20), adolescents who reported stopping the behaviour over the course of a year (NSSI Stop group, n = 40), and a comparison group of adolescents who did not report engaging in NSSI (n = 60). Using a 3 (NSSI Maintain, NSSI Stop, and Comparison) X 2 (Gender) X 2 (Time 1 and Time 2) repeated measures multiple analysis of variance (MANOVA), results indicated a significant group by time interaction, showing group differences with respect to body shame and body surveillance over time. Specifically, both NSSI groups reported significantly greater body shame and body surveillance over time than the non-NSSI group. Additionally, the NSSI Maintain group reported significantly greater body surveillance at T2 when compared to the NSSI Stop and non-NSSI group. The NSSI Maintain group also reported significantly more emotion dysregulation difficulties and depressive symptoms at T2 when compared to the NSSI Stop and non NSSI group. The influence of body objectification as a core intrapersonal risk factor related to the maintenance and cessation of NSSI behaviour is discussed, as are clinical implications considering body objectification as an important variable in prevention and treatment efforts. PMID- 26157481 TI - The effects of nonsuicidal self-injury on parenting behaviors: a longitudinal analyses of the perspective of the parent. AB - BACKGROUND: The present study is the first to examine predictors and consequences of nonsuicidal self-injury (NSSI) in adolescence using parent-reported data in a longitudinal design. Across three time points, we examined the reciprocal effects of parent-reported parenting behaviors as they are related to adolescents' NSSI. METHODS: The present study is a three-wave prospective study in a large sample of community adolescents and their parents. At time 1 (age 12), the sample consisted of 1396 adolescent reports and 1438 parent reports. Time 2 (age 13) included 827 adolescent and 936 parent reports. At time 3 (age 14), 754 adolescent and 790 parent reports were obtained. Engagement in NSSI (adolescent report) was determined by an affirmative response to the item 'Have you intentionally injured yourself (e.g., cut, burn, scratch) this year, without the intent to die?'. Parental awareness of NSSI at age 13 and 14 was examined using a single-item screening question. Parenting behaviors were examined by the parent versions of the Parental Behavior Scale. RESULTS: Results showed that although NSSI was reported by 10 % of the adolescents, only 3 % of the parents were aware of the NSSI behaviors of their children. Cross-lagged analyses showed a reciprocal relationship between NSSI and parenting behaviors over time. We found a significant effect of both positive parenting and controlling parenting on the presence of NSSI at time 2. But vice versa NSSI also has an effect on parenting behaviors over time. Results showed that NSSI at time 1 has an impact on controlling parenting behaviors, namely punishment at time 2. NSSI at time 2 showed an impact on parent's perception of positive parenting, parental rule setting, punishment and harsh punishment. CONCLUSIONS: The present study examined predictors and consequences of NSSI in a longitudinal design, and emphasized the importance of examining reciprocal interactions between NSSI and parenting behaviors. Furthermore, it is the first study to examine parent-reported data in a longitudinal design and gives insight into parents' perspectives. PMID- 26157482 TI - The Ottawa Self-Injury Inventory: Evaluation of an assessment measure of nonsuicidal self-injury in an inpatient sample of adolescents. AB - BACKGROUND: The Ottawa Self-Injury Inventory (OSI) is a self-report measure that offers a comprehensive assessment of nonsuicidal self-injury (NSSI), including measurement of its functions and addictive features. In a preliminary investigation of self injuring college students who completed the OSI, exploratory analysis revealed four function factors (Internal Emotion Regulation, Social Influence, External Emotion Regulation and Sensation Seeking) and a single Addictive Features factor. Rates of NSSI are particularly high in inpatient psychiatry youth. The OSI can assistin both standardizing assessment regarding functions and potential addictive features and aid case formulation leading to informed treatment planning. This report will describe a confirmatory factor analysis (CFA) of the OSI on youth hospitalized in a psychiatric unit in southwestern Ontario. METHODS: Demographic and self-report data were collected from all youth consecutively admitted to an adolescent in-patient unit who provided consent or assent. RESULTS: The mean age of the sample was 15.71 years (SD = 1.5) and 76 (81 %) were female. The CFA proved the same four function factors relevant, as in the previous study on college students (chi (2)(183) = 231.98, p = .008; chi (2)/df = 1.27; CFI = .91; RMSEA = .05). The model yielded significant correlations between factors (rs = .44-.90, p < .001). Higher NSSI frequency was related to higher scores on each function factor (rs = .24-.29, p < .05), except the External Emotion Regulation factor (r = .11, p > .05). The factor structure of the Addictive Features function was also confirmed (chi (2)(14) = 21.96, p > .05; chi (2)/df = 1.57; CFI = .96; RMSEA = .08). All the items had significant path estimates (.52 to .80). Cronbach's alpha for the Addictive Features scale was .84 with a mean score of 16.22 (SD = 6.90). Higher Addictive Features scores were related to more frequent NSSI (r = .48, p < .001). CONCLUSIONS: Results show further support for the OSI as a valid and reliable assessment tool in adolescents, in this case in a clinical setting, where results can inform case conceptualization and treatment planning. PMID- 26157483 TI - The impact of attitudes as a mediator between sense of autonomy and help-seeking intentions for self-injury. AB - BACKGROUND: Self-injury is a complex issue, further complicated by the fact that up to half of young people who self-injure do not receive help. Young people who do receive help for self-injury claim they prefer to access family and friends over more formal sources of help. This original research set out to examine the influence of negative attitudes to professional help and a sense of autonomy on help-seeking intentions. METHODS: A cross-section of 220 university students and young adults from the community (Students = 131, other participants = 89; mean age = 24.64) completed anonymous online questionnaires measuring self-injurious behaviour and mental health related problems, attitudes toward seeking professional mental health help, autonomy, and intentions to seek help for self injury. Two separate mediation models were tested using a bootstrapping approach to investigate intentions to seek help - one on mental health problems, and one specifically on self-injury. RESULTS: More positive attitudes to help-seeking were significantly associated with greater intentions to seek help, while higher perceived autonomy was associated with lower intentions to seek help. Attitudes fully mediated the negative relationship between autonomy and willingness to seek help for self-injury. The model also maintained partial mediation for willingness to seek help for other mental health problems, beyond self-injury. Current self injurers expressed significantly more negative attitudes toward help-seeking compared to past self-injurers and those with no history of self-injury. Similarly, current self-injurers reported being less likely to seek help from anyone compared to both other groups. CONCLUSIONS: This study appears to be the first to set out to compare self-injurers' attitudes to help-seeking directly with those of non-self-injurers, and the first to show that attitudes mediate the relationship between autonomy and help-seeking. The findings provide evidence that will assist development of interventions targeting negative attitudes toward seeking professional help, in order to increase help-seeking among self-injurers who would otherwise not receive treatment. PMID- 26157484 TI - Prevalence, correlates, and prospective predictors of non-suicidal self-injury among New Zealand adolescents: cross-sectional and longitudinal survey data. AB - Non-suicidal self-injury (NSSI) is common among adolescents and linked to many maladaptive outcomes. This study aimed to assess the prevalence and correlates of NSSI among a community sample of New Zealand adolescents. A self-report questionnaire was administered to adolescents at time 1 (N = 1162, mean age = 16.35), and approximately five months later (time 2, N = 830, mean age = 16.49). Prevalence and bivariate correlations were assessed at both time points, and cross-lag correlations using matched data (N = 495, mean age = 16.23). Lifetime history of NSSI was 48.7 % (females 49.4 %, males 48 %). Consistent with previous international research, NSSI was associated with higher Alexithymia, depression, anxiety, bullying, impulsivity, substance abuse, abuse history and sexuality concerns and lower mindfulness, resilience and self-esteem. Cross-lag correlations suggested NSSI is directly (perhaps causally) related to psychological vulnerability in various domains (e.g., increased depression and lower self-esteem), while bullying may be more distal to NSSI, rather than a proximal predictor. PMID- 26157485 TI - PAX5-KIAA1549L: a novel fusion gene in a case of pediatric B-cell precursor acute lymphoblastic leukemia. AB - BACKGROUND: In B-cell precursor acute lymphoblastic leukemia (BCP-ALL) PAX5, a transcription factor pivotal for B-cell commitment and maintenance, is frequently affected by genetic alterations. In 2-3 % of the cases PAX5 rearrangements result in the expression of oncogenic fusion genes. The encoded chimeric proteins consist of the N-terminal PAX5 DNA-binding paired domain, which is fused to the C terminal domains of a remarkable heterogeneous group of partner proteins. RESULTS: Employing fluorescence in situ hybridization and molecular methods PAX5 KIAA1549L was identified as novel fusion gene in a case of pediatric BCP-ALL. CONCLUSION: Our report underlines the high diversity of PAX5 fusion partners in BCP-ALL and we describe the second involvement of KIAA1549L in a genetic rearrangement in acute leukemia. PMID- 26157486 TI - Preimplantation genetic screening of blastocysts by multiplex qPCR followed by fresh embryo transfer: validation and verification. AB - BACKGROUND: Aneuploidy is an important etiology of implantation failure and quantitative real-time polymerase chain reaction (qPCR) seems a promising preimplantation genetic screening (PGS) technology to detect aneuploidies. This verification study aimed at verifying the impact on reproductive outcomes in in vitro fertilization (IVF) cycles using fresh embryo transfer (FET) in which the embryos were selected by blastocyst biopsy with qPCR-based PGS in our settings. RESULTS: A total of 13 infertile couples with more than once failed in vitro fertilization were enrolled during July to October of 2014. PGS was conducted by qPCR with selectively amplified markers to detect common aneuploidies (chromosomes 13, 18, 21, X, and Y). The design of the qPCR molecular markers adopted the locked nucleic acid (LNA) strategy. The blastocyst biopsy was performed on Day 5/6 and the PGS was done on the same day, which enabled FET. A total of 72 blastocysts were biopsied. Successful diagnoses were established in all embryos and the rate of successful diagnosis was 100 %. The aneuploidy rate was 38.9 % (28/72). 28 embryos were transferred. The clinical pregnancy rate was 61.5 % (8/13) per cycle. Early first trimester abortion was encountered in 1 and the ongoing pregnancy rate was 53.8 % (7/13) per cycle. CONCLUSION: This study verified the favorable outcome of adopting PGS with qPCR + FET in our own setting. Expanding the repertoire of aneuploidies being investigated (from a limited set to all 24 chromosomes) is underway and a randomized study by comparing qPCR and other PGS technologies is warranted. PMID- 26157487 TI - Thyroid hormones and functional outcomes after ischemic stroke. AB - BACKGROUND: Stroke is the fifth leading cause of death and the primary cause of long-term adult disability in the United States. Increasing evidence suggests that low T3 levels immediately following acute ischemic stroke are associated with greater stroke severity, higher mortality rates, and poorer functional outcomes. Prognosis is also poor in critically ill hospitalized patients who have non-thyroidal illness syndrome (NTIS), where T3 levels are low, but TSH is normal. However, data regarding the association between TSH levels and functional outcomes are contradictory. Thus, this study investigated the role of TSH on stroke outcomes, concomitantly with T3 and T4. FINDINGS: In this work, blood was collected from patients with radiologically confirmed acute ischemic stroke at 24+/-6 hours post-symptom onset and serum levels of TSH, free T3, and free T4 were measured. Stroke outcomes were measured at discharge, 3 and 12 months using the modified Rankin scale and modified Barthel Index as markers of disability. Though we found that lower levels of free T3 were associated with worse prognosis at hospital discharge, and at 3 and 12 months post-stroke, none of these outcomes held after multivariate analysis. Thus, it is likely that thyroid hormones are associated with other factors that impact stroke outcomes, such as sex, age and stroke etiology. CONCLUSIONS: This study found that lower levels of free T3 were associated with poorer outcomes at hospital discharge, and at 3 and 12 months post stroke, however, these associations diminished after correction for other known predictors of stroke outcome. Thyroid hormones have a complex relationship with ischemic stroke and stroke recovery, which merits further larger investigations. PMID- 26157488 TI - The ratio of serum free triiodothyronine to free thyroxine in children: a retrospective database survey of healthy short individuals and patients with severe thyroid hypoplasia or central hypothyroidism. AB - BACKGROUND: The ratio of serum free triiodothyronine (FT3) to free thyroxine (FT4) has been shown to be constant in healthy adults. However, this ratio has been found to be decreased in athyreotic adult patients on levothyroxine (L-T4) supplementation. In order to better evaluate thyroid-related pathologies in children as well as to establish a reference range, we investigated the FT3/FT4 ratio in a pediatric population. Furthermore, we evaluated this ratio in children with congenital hypothyroidism as well as those with central hypothyroidism. METHODS: A reference range for the FT3/FT4 ratio was obtained from 129 Japanese children (3-17 y) with idiopathic short stature who were designated as the 'Control' group. Patients with congenital hypothyroidism due to athyreosis or severe thyroid hypoplasia (designated as 'A/Hypoplasia'), as well as patients with central hypothyroidism ('Central'), were recruited from the institutional database. For each group, the mean FT3/FT4 ratio was obtained. RESULTS: In the Control group, the FT3/FT4 ratio was 3.03 +/- 0.38 10(-2) pg/ng (mean +/- standard deviation) with no age or gender differences. A/Hypoplasia patients showed a significantly decreased mean FT3/FT4 ratio (2.17 +/- 0.33, P < 0.001) compared to Control patients, with decreased FT3 and elevated FT4 levels. The Central group also showed a significantly decreased FT3/FT4 ratio (2.55 +/- 0.45, P < 0.001) compared to the Control group, with decreased FT3 and equivalent FT4 levels. CONCLUSIONS: The FT3/FT4 ratio appears to be constant between the ages of 3-17 y. Children on L-T4 due to congenital thyroid a/hypoplasia or central hypothyroidism have a decreased FT3/FT4 ratio compared to short normal children. PMID- 26157489 TI - Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1. AB - BACKGROUND: The organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans. METHODS: We applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1 activity. RESULTS: We identified 16 amino acid substitutions potentially causing loss of OCT1 function and analyzed them together with five amino acid substitutions that were not expected to affect OCT1 function. The variants constituted 16 major alleles and 14 sub-alleles. Six major alleles showed improper subcellular localization leading to substrate-wide loss in activity. Five major alleles showed correct subcellular localization, but substrate-specific loss of activity. Striking differences were observed in the frequency of loss of OCT1 activity worldwide. While most East Asian and Oceanian individuals had completely functional OCT1, 80 % of native South American Indians lacked functional OCT1 alleles. In East Asia and Oceania the average nucleotide diversity of the loss-of-function variants was much lower than that of the variants that do not affect OCT1 function (ratio of 0.03) and was significantly lower than the theoretically expected heterozygosity (Tajima's D = -1.64, P < 0.01). CONCLUSIONS: Comprehensive genetic analyses showed strong global variations in the frequency of loss of OCT1 activity with selection pressure for maintaining OCT1 activity in East Asia and Oceania. These results not only enable pharmacogenetically-based optimization of drug treatment worldwide, but may help elucidate the functional role of human OCT1. PMID- 26157490 TI - Angiosarcoma of the Head and Neck. AB - Introduction Angiosarcoma of the head and neck is a rare vascular sarcoma associated with high rates of local recurrence and distant metastasis and a poor prognosis. Objective We describe our experience treating patients with angiosarcoma of the head and neck to evaluate the outcomes, patterns of failure, and current treatments. Methods We identified six patients with angiosarcoma of the head and neck and treated at our institution between 2000 and 2013. We compared our results to the literature from 1979 to 2013. Results Mean follow-up was 42 months. Local recurrence rate was 50% with disease-specific survival and 2 year disease-free survival rates of 33.3 and 20%, respectively. Prognostic factors included tumor size > 5 cm and surgical margin status, with no correlation between histologic grade and survival. Combined-modality therapy was only used for aggressive tumors with positive surgical margins but is suggested to improve local control and overall survival. Conclusions Our data series supports that angiosarcoma of the head and neck has a high rate of recurrence and is associated with a poor prognosis, despite current combined-modality therapy. The study highlights the importance of attaining negative margins during surgical resection, the utility of adjuvant therapies, as well as the need for continued research in developing new management strategies. PMID- 26157491 TI - Rhinosinusal Polyposis and Inverted Papilloma: A Morphometric Comparative Study. AB - Introduction Nasal obstruction is one of the main rhinologic complaints, and two diseases must be investigated as differential diagnosis: rhinosinusal polyposis and inverted papilloma. Using traditional methods, the differential diagnosis between these diseases may be difficult. The morphometric study may be a useful tool for differential diagnosis and to define prognosis. Objective Calculate the morphometric values of rhinosinusal polyposis and inverted papilloma and compare the average of variables obtained between the groups. Methods The nasal mucus of 10 patients who had surgery in the Department of Otorhinolaryngology and Surgery of Head and Neck was studied; 5 had rhinosinusal polyposis and 5 had inverted papilloma. After the capture and print of corresponding data of each slide, the largest and smallest diameters of the nuclei were measured and the morphometric variables were calculated: average diameter, perimeter, ratio between largest and smallest diameter, volume, area, ratio of volume to area, form coefficient, contour index, and eccentricity. Results We found a significant difference (p < 0.05) between the two groups in the following morphometric variables: largest diameter, smallest diameter, average diameter, volume, area, perimeter, and ratio of volume to area, indicating that these parameters can be useful in diagnostic differentiation between these diseases. Conclusion We founded morphometric variables higher in patients with inverted papilloma, which can be related to the neoplastic origin of the inverted papilloma. The analysis of nuclear parameters is an instrument of great value in the differential diagnosis between rhinosinusal polyposis and inverted papilloma. PMID- 26157492 TI - Venous Thromboembolism-Incidence of Deep Venous Thrombosis and Pulmonary Embolism in Patients with Head and Neck Cancer: A Tertiary Care Experience in Pakistan. AB - Introduction Although venous thromboembolism (VTE) is seen with morbidity and mortality in various surgical specialties, scarce data are available in the head and neck surgery domain. Objective We aim to determine the incidence of VTE in patients receiving surgery for head and neck cancer. Methods Four hundred thirteen patients who underwent head and neck surgery procedures between 2005 and 2013 were reviewed retrospectively. All patients with head and neck surgery had received thromboprophylaxis (i.e., compression stockings and subcutaneous heparin). Patient demographics, operating time, and length of hospital stay were analyzed. The incidence of symptomatic deep venous thrombosis (DVT) and pulmonary embolism (PE) during the initial postoperative hospitalization was assessed. Results Twelve patients were identified who developed VTE. Three patients developed DVT, and nine developed PE. The incidence of DVT and PE was 0.72 and 2.17%, respectively. Interestingly, all of these patients had undergone excision of extensive head and neck cancers accompanied by a reconstructive procedure. Patients who developed PE had a longer hospital stay compared with those who only had DVT. There were overall three mortalities in the nine patients who developed PE. Conclusion Although VTE has a low incidence, it is a known complication of extensive head and neck surgeries with life-threatening outcomes. We recommend early mobilization and physiotherapy with the possible aid from appropriate mechanical and pharmacologic thromboprophylaxis. PMID- 26157493 TI - Ambient Noise in Emergency Rooms and Its Health Hazards. AB - Introduction The occupational risk due to high levels of noise in the hospital environment has been recognized, and the National Agency of Sanitary Surveillance of the Ministry of Health recommends evaluation and control of noise in hospital areas. Objectives To assess the sound environment in the emergency ward of a general trauma reference hospital in the city of Curitiba, Parana State, Brazil. Methods In this descriptive study, noise levels were assessed on mornings, afternoons, and evenings using an integrating Bruel & Kjaer (Denmark) calibrated sound level meter, type 2230. Ten indoor points in the emergency ward were assessed; the helicopter as well as several available pieces of equipment in the ward were assessed individually. Results Noise levels in sound pressure level ambiance [dBA] ranged from 56.6 to 68.8. The afternoon period was the noisiest. The helicopter at 119 dBA and the cast saw at 90 dBA were the noisiest equipment, and the lowest noise level found was the activated oximeter at 61.0 dBA. Conclusion In all assessed points, noise levels were above the comfort levels recommended by the Brazilian Association of Technical Standards (1987), which may harm users' and professionals' health as well as influence professional performance in the emergency ward. Sound pressure levels of the helicopter and cast saw reach high hearing hazard levels, requiring professionals to use individual protection equipment, and point to the need for creation and implementation of effective control measures of noise levels in emergency wards. PMID- 26157494 TI - Hearing Aid Use and Adherence to Treatment in a Publicly-Funded Health Service from the City of Sao Paulo, Brazil. AB - Introduction Periodic follow-up appointments are important to ensure long-term effectiveness of rehabilitation with hearing aids. However, not all users are able to maintain adherence to recommendations prescribed during the fitting process and some do not attend those appointments, which compromises the effectiveness of treatment. Objective Compare hearing aid use after 1 year between subjects who did not attend a follow-up evaluation appointment at a publicly-funded health service (nonattenders) and those who attended the appointment (attenders). Reasons for nonuse of hearing aids and unscheduled appointments were also analyzed. Methods Prospective observational cross sectional study. Nonattenders and attenders in a follow-up evaluation appointment were interviewed by telephone about hearing aid use, reasons for nonuse, and unscheduled appointments. Results The nonattenders group consisted of 108 subjects and the attenders group had 200 subjects; in both groups, most users kept bilateral use but the nonuse rate was higher in nonattenders. The main reason for nonuse of hearing aids among nonattenders was health problems; fitting problems was the main reason for nonuse in the attenders group. Health problems and issues like unavailable companion and transportation difficulties were the reasons for unscheduled follow-up appointments. Conclusion Nonattenders had a greater nonuse rate and were more likely to abandon hearing aid use. Measures to increase hearing aid use and adherence to prescribed recommendations are also necessary to ensure long-term effectiveness of rehabilitation with hearing aids. PMID- 26157495 TI - Relationship between Otolaryngologic Complaints and Systemic Comorbidities Observed in a Group of Hearing Aid Users. AB - Introduction Optimization of the selection, adaptation, and benefit of hearing aids is necessary to characterize and manage hearing loss, user expectations, otolaryngologic symptoms, and systemic comorbidities. Objective To compare the occurrence of otologic complaints, systemic diseases, and effective use of hearing aids in men and women with deafness. Methods Patients from a Unified Health System-accredited hearing health service, who reported problems in adapting to their hearing aids, were evaluated by a physician and audiologist. An anamnesis, ENT evaluation, and audiological evaluation were performed. Results During the data collection period, 278 subjects came in for follow-up visits; of these, 61 (21%) reported otologic or operational problems with their equipment. The most prevalent type of hearing loss was basocochlear, a characteristic of presbycusis, in both men and women; the most frequently reported comorbidities were hypercholesterolemia (more significant in women) and hypertension (more significant in men). Fourteen subjects reported using their device discontinuously, with no significant difference between genders; the reasons for discontinuation of use were itching and ringing, with more complaints from women. Conclusion The incidence of systemic and audiological complaints is high in this population. These patients should be evaluated thoroughly, as resolutions of these complaints can contribute to improving the quality of life and assist in the process of hearing aid fitting. PMID- 26157496 TI - Study of the Hearing Threshold of Dance Teachers. AB - Introduction High sound pressure levels can cause hearing loss, beginning at high frequencies. Objective To analyze the hearing thresholds of dance teachers. Methods This study had a cross-sectional, observational, prospective, and descriptive design. Conventional and high-frequency hearing evaluations were performed with dance teachers and subjects in the control group. Results In all, 64 individuals were assessed, 32 in the research group and 32 in the control group. Results showed that individuals in the research group had hearing loss at frequencies between 4 and 8 kHz, but no significant difference was found between groups. Frequency analysis showed that individuals in the control group had higher thresholds than individuals in the research group at the frequency of 0.25 kHz. In the control group, men showed higher thresholds than women at the frequency of 9 kHz. Conclusion A low prevalence of hearing loss was found, with no difference between teachers and subjects from the control group. No difference was found for hearing thresholds at high frequencies between groups. Results have been partially affected by sex. PMID- 26157497 TI - The Effects of Unilateral Adaptation of Hearing Aids on Symptoms of Depression and Social Activity Constraints of Elderly. AB - Introduction Hearing loss is one of the most common problems in the elderly population. Besides compromising oral communication, it directly affects social relations and prevents elderly patients from living actively in society, possibly leading to the onset of depression or other conditions. Objective To analyze the effects of unilateral adaptation of hearing aids on symptoms of depression and the social activity constraints of elderly subjects with hearing impairment. Methods The sample consisted of elderly subjects with hearing loss who did not use hearing aids. Data were collected in two phases. Initially, all participants underwent an audiological assessment and answered the Hearing Handicap Inventory for Elderly (summarized version) and the Geriatric Depression Scale. All subjects participated in the selection and hearing aid adaptation processes and became monaural hearing aid users. After 30 days of hearing aid use, they were assessed with the same instruments. The results of the questionnaires before and after hearing aid adaptation were compared. Results The sample consisted of 13 individuals, between 60 and 90 years old (mean 72.85 +/- 11.05 years). Data analysis showed that there was significant improvement in social activity constraints (p < 0.001) and in symptoms of depression (p = 0.031). Conclusion Results show that, in the sample studied, unilateral hearing aid adaptation reduced social activity constraints and depression symptoms. PMID- 26157498 TI - Reflux Laryngitis: Correlation between the Symptoms Findings and Indirect Laryngoscopy. AB - Introduction The indirect laryngoscopy has an important role in the characterization of reflux laryngitis. Although many findings are nonspecific, some strongly suggest that the inflammation is the cause of reflux. Objective The aim of this study was to evaluate the correlation between reflux symptoms and the findings of indirect laryngoscopy. Methods We evaluated 27 patients with symptoms of pharyngolaryngeal reflux disease. Results Laryngoscopy demonstrated in all patients the presence of hypertrophy of the posterior commissure and laryngeal edema. The most frequent symptoms were the presence of dry cough and foreign body sensation. Conclusion There was a correlation between the findings at laryngoscopy and symptoms of reflux. PMID- 26157499 TI - Effectiveness of a Vestibular Rehabilitation Protocol to Improve the Health Related Quality of Life and Postural Balance in Patients with Vertigo. AB - Introduction Dizziness can be characterized as a balance disorder that causes discomfort, leading to several functional limitations. Currently, vestibular rehabilitation has been highlighted as a possible treatment. Objective Analyze the effects of completing a vestibular rehabilitation treatment protocol on quality of life and postural balance in patients with vestibular complaints, as well as to compare these effects between the patients taking or not taking antivertigo drugs. Methods A nonrandomized controlled trial was performed with 20 patients previously diagnosed with vestibular diseases. Information regarding vertigo symptoms, quality of life as assessed through the Dizziness Handicap Inventory, visual analog scale of dizziness, and stabilometry using force platform was collected. Patients were treated for 12 weeks by a custom protocol. The sample was divided into two groups according to the use (medicated group, n = 9) or not (control group, n = 11) of antivertigo drugs. Results There was improvement in quality of life (p < 0.001) and intensity of dizziness (p = 0.003) with the intervention. An improvement of postural balance was observed through functional tests. However, no statistically significant difference was noted in stabilometry. When both groups were compared, no statistically significant differences between the variations of the variables analyzed were found in the re evaluation session. Conclusion Quality of life and postural balance are improved with intervention. However, this improvement is not associated with pharmacologic treatment. PMID- 26157500 TI - Voice Outcome after Gore-Tex Medialization Thyroplasty. AB - Introduction Although medialization thyroplasty utilizing Gore-Tex (Gore and Associates, Newark, Delaware, United States) has been discussed in the literature, few reports have assessed voice quality afterward, and they did not use a full assessment protocol. Objective To assess the improvement in voice quality after medialization thyroplasty utilizing Gore-Tex in patients with glottic insufficiency of variable etiology. Methods Eleven patients with glottic insufficiency of different etiologies that failed compensation were operated by type 1 thyroplasty utilizing Gore-Tex. Pre- and postoperative (1 week, 3 months, and 6 months) voice assessment was done and statistical analysis was performed on the results. Results In all postoperative assessments, there was significant improvement in the grade of dysphonia (p < 0.004) and highly significant reduction in the size of glottic gap and prolongation of maximum phonation time (p < 0.0001). The difference in voice parameters in the early (1 week) and the late (3 and 6 months) postoperative period was not significant. None of the patients developed stridor or shortness of breath necessitating tracheotomy, and there was no implant extrusion in any patient during the study period. Conclusion Gore-Tex medialization provides reliable results for both subjective and objective voice parameters. It leads to a satisfactory restoration of voice whatever the etiology of glottic incompetence is. This technique is relatively easy and does not lead to major complications. Further studies with larger number of patients and more extended periods of follow-up are still required to assess the long-term results of the technique regarding voice quality and implant extrusion. PMID- 26157501 TI - Transient Evoked and Distortion Product Otoacoustic Emissions in a Group of Neonates. AB - Introduction The most commonly used method in neonatal hearing screening programs is transient evoked otoacoustic emissions in the first stage of the process. There are few studies comparing transient evoked otoacoustic emissions with distortion product, but some authors have investigated the issue. Objective To correlate the results of transient evoked and distortion product otoacoustic emissions in a Brazilian maternity hospital. Methods This is a cross-sectional, comparative, and prospective study. The study included 579 newborns, ranging from 6 to 54 days of age, born in a low-risk maternity hospital and assessed for hearing loss. All neonates underwent hearing screening by transient evoked and distortion product otoacoustic emissions. The results were analyzed using the Spearman correlation test to relate the two procedures. Results The pass index on transient evoked otoacoustic emissions was 95% and on distortion product otoacoustic emissions was 91%. The comparison of the two procedures showed that 91% of neonates passed on both procedures, 4.5% passed only on transient evoked otoacoustic emissions, 0.5% passed only on distortion product otoacoustic emissions, and 4% failed on both procedures. The inferential analysis showed a significant strong positive relationship between the two procedures. Conclusion The failure rate was higher in distortion product otoacoustic emissions when compared with transient evoked; however, there was correlation between the results of the procedures. PMID- 26157502 TI - Tinnitus Neural Mechanisms and Structural Changes in the Brain: The Contribution of Neuroimaging Research. AB - Introduction Tinnitus is an abnormal perception of sound in the absence of an external stimulus. Chronic tinnitus usually has a high impact in many aspects of patients' lives, such as emotional stress, sleep disturbance, concentration difficulties, and so on. These strong reactions are usually attributed to central nervous system involvement. Neuroimaging has revealed the implication of brain structures in the auditory system. Objective This systematic review points out neuroimaging studies that contribute to identifying the structures involved in the pathophysiological mechanism of generation and persistence of various forms of tinnitus. Data Synthesis Functional imaging research reveals that tinnitus perception is associated with the involvement of the nonauditory brain areas, including the front parietal area; the limbic system, which consists of the anterior cingulate cortex, anterior insula, and amygdala; and the hippocampal and parahippocampal area. Conclusion The neuroimaging research confirms the involvement of the mechanisms of memory and cognition in the persistence of perception, anxiety, distress, and suffering associated with tinnitus. PMID- 26157503 TI - Wegener Granulomatosis: Otologic Manifestation as First Symptom. AB - Introduction Wegener granulomatosis is a systemic vasculitis affecting small and medium-sized vessels of the upper and lower respiratory tract and kidneys. Objective To describe a case of Wegener disease with atypical manifestation. Resumed Report We describe the case of a 50-year-old woman with chronic otitis media and sensorineural hearing loss as the primary symptoms, without other manifestations. Conclusion In cases of acute ear manifestations with or without hearing loss and with poor response to usual treatments, Wegener granulomatosis should be included among the possible etiologies. After adequate diagnoses and treatment of this rare disease, there was favorable evolution. PMID- 26157504 TI - Telephone Usage and Cochlear Implant: Auditory Training Benefits. AB - Introduction Difficulties with telephone use by adult users of cochlear implants (CIs) are reported as a limitation in daily life. Studies to improve the speech understanding of CI users on the telephone are scarce in the Brazilian scientific literature. Objective To develop and evaluate the effectiveness of a training program of auditory abilities on the telephone for an adult CI user. Resumed Report The subject was a 55-year-old woman with a degree in accounting who used a CI for 24 months. The program consisted of three stages: pretraining evaluation, eight sessions of advanced auditory abilities training, and post-training evaluation. Auditory abilities with CI were evaluated before and after training in three conditions: sound field, telephone with the speech processor in the microphone function, and telephone with the speech processor in the telecoil function. Speech recognition was assessed by three different lists: one with monosyllabic and dissyllabic words, another with nonsense syllables, and another one with sentences. The Client Oriented Scale of Improvement (COSI) was used to assess whether the needs established by the CI user in everyday telephone use situations improved after training. The auditory abilities training resulted in a relevant improvement in the percentage of correct answers in speech tests both in the telephone use conditions and in the sound field condition. Conclusion The results obtained with the COSI inventory indicated a performance improvement in all situations presented at the beginning of the program. PMID- 26157505 TI - Thickened Pituitary Stalk Associated with a Mass in the Sphenoidal Sinus: An Alarm to Suspect Hypophysitis by Immunoglobulin G4? AB - Introduction Hypophysitis is a chronic inflammation of the pituitary gland of complex and still incompletely defined pathogenesis. It belongs to the group of non-hormone-secreting sellar masses, sharing with them comparable clinical presentation and radiographic appearance. Objectives Describe the case of immunoglobulin G4 (IgG4)-related hypophysitis presenting as a mass in the sphenoid sinus. Resumed Report A 40-year-old Brazilian man had a diagnosis of central diabetes insipidus since 2001 associated with pituitary insufficiency. Pituitary magnetic resonance imaging revealed a centered pituitary stalk with focal nodular thickening and the presence of heterogeneous materials inside the sphenoid sinus. The patient was treated with testosterone replacement therapy. Laboratory results revealed increased IgG4 serum. Conclusion IgG4-related hypophysitis should be considered in patients with pituitary insufficiency associated with sellar mass and/or thickened pituitary stalk. IgG4 serum measurement for early diagnosis of IgG4-related hypophysitis should be performed. PMID- 26157506 TI - Antibiotic Resistant and Virulence Determinants of Staphylococcus haemolyticus C10A as Revealed by Whole Genome Sequencing. AB - Staphylococcus haemolyticus is one of the pathogens that harbor a high level of antibiotic resistance. Here, we highlighted the potential determinants for multidrug resistance and virulence from the draft genome of Staphylococcus haemolyticus strain C10A, isolated from a patient with chronic obstructive pulmonary disease exacerbation. PMID- 26157507 TI - GLAD: an Online Database of Gene List Annotation for Drosophila. AB - We present a resource of high quality lists of functionally related Drosophila genes, e.g. based on protein domains (kinases, transcription factors, etc.) or cellular function (e.g. autophagy, signal transduction). To establish these lists, we relied on different inputs, including curation from databases or the literature and mapping from other species. Moreover, as an added curation and quality control step, we asked experts in relevant fields to review many of the lists. The resource is available online for scientists to search and view, and is editable based on community input. Annotation of gene groups is an ongoing effort and scientific need will typically drive decisions regarding which gene lists to pursue. We anticipate that the number of lists will increase over time; that the composition of some lists will grow and/or change over time as new information becomes available; and that the lists will benefit the scientific community, e.g. at experimental design and data analysis stages. Based on this, we present an easily updatable online database, available at www.flyrnai.org/glad, at which gene group lists can be viewed, searched and downloaded. PMID- 26157508 TI - MethPed: a DNA methylation classifier tool for the identification of pediatric brain tumor subtypes. AB - BACKGROUND: Classification of pediatric tumors into biologically defined subtypes is challenging, and multifaceted approaches are needed. For this aim, we developed a diagnostic classifier based on DNA methylation profiles. RESULTS: Methylation data generated by the Illumina Infinium HumanMethylation 450 BeadChip arrays were downloaded from the Gene Expression Omnibus (n = 472). Using the data, we built MethPed, which is a multiclass random forest algorithm, based on DNA methylation profiles from nine subgroups of pediatric brain tumors. DNA from 18 regional samples was used to validate MethPed. MethPed was additionally applied to a set of 28 publically available tumors with the heterogeneous diagnosis PNET. MethPed could successfully separate individual histology tumor types at a very high accuracy (kappa = 0.98). Analysis of a regional cohort demonstrated the clinical benefit of MethPed, as confirmation of diagnosis of tumors with clear histology but also identified possible differential diagnoses in tumors with complicated and mixed type morphology. CONCLUSIONS: We demonstrate the utility of methylation profiling of pediatric brain tumors and offer MethPed as an easy-to-use toolbox that allows researchers and clinical diagnosticians to test single samples as well as large cohorts for subclass prediction of pediatric brain tumors. This will immediately aid clinical practice and importantly increase our molecular knowledge of these tumors for further therapeutic development. PMID- 26157509 TI - Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX. AB - BACKGROUND: Profound methylation of CpG islands constitutes a distinct molecular subtype of colorectal cancer (CRC). The frequencies of methylation in CRC vary according to clinico-pathological characteristics including sex. However, interaction between these characteristics and prognostic influence of methylation status has not been clearly defined. We have investigated the prognostic role of promoter methylation using eight CpG island methylator phenotype (CIMP) markers in 497 stage II or III CRC patients who underwent curative resection followed by adjuvant FOLFOX. Overall survival (OS) and disease-free survival (DFS) were compared between subgroups classified by methylation status, and interactions with clinico-pathological features were analyzed. RESULTS: CIMP-high (>=5 methylated loci) and concurrent methylation in NEUROG1 and CDKN2A (p16) were found in 5.8 and 7.9 % of patients, respectively. Although CIMP-high status was not associated with survival, concurrent methylation in NEUROG1 and CDKN2A (p16) was associated with shorter OS and DFS. Moreover, the prognostic role of the concurrent methylation was different among sex. The negative prognostic impact was only observed in male but not in female (interaction p value = 0.026 for OS and 0.011 for DFS). In male, the 5-year OS was 61.6 % in concurrent methylation (+) and 91.7 % in concurrent methylation (-) (p < 0.001) whereas it was 95.0 and 92.8 % in female, respectively (p = 0.78). CONCLUSIONS: Concurrent methylation in NEUROG1 and CDKN2A is associated with poor survival in CRC treated with adjuvant FOLFOX. Interaction analysis indicates that the prognostic role is different according to sex. PMID- 26157510 TI - The necessity of connection structures in neural models of variable binding. AB - In his review of neural binding problems, Feldman (Cogn Neurodyn 7:1-11, 2013) addressed two types of models as solutions of (novel) variable binding. The one type uses labels such as phase synchrony of activation. The other ('connectivity based') type uses dedicated connections structures to achieve novel variable binding. Feldman argued that label (synchrony) based models are the only possible candidates to handle novel variable binding, whereas connectivity based models lack the flexibility required for that. We argue and illustrate that Feldman's analysis is incorrect. Contrary to his conclusion, connectivity based models are the only viable candidates for models of novel variable binding because they are the only type of models that can produce behavior. We will show that the label (synchrony) based models analyzed by Feldman are in fact examples of connectivity based models. Feldman's analysis that novel variable binding can be achieved without existing connection structures seems to result from analyzing the binding problem in a wrong frame of reference, in particular in an outside instead of the required inside frame of reference. Connectivity based models can be models of novel variable binding when they possess a connection structure that resembles a small-world network, as found in the brain. We will illustrate binding with this type of model with episode binding and the binding of words, including novel words, in sentence structures. PMID- 26157511 TI - Transition dynamics of EEG-based network microstates during mental arithmetic and resting wakefulness reflects task-related modulations and developmental changes. AB - We studied how maturation influences the organization of functional brain networks engaged during mental calculations and in resting state. Surface EEG measurements from 20 children (8-12 years) and 25 students (21-26 years) were analyzed. Interregional synchronization of brain activity was quantified by means of Phase Lag Index and for various frequency bands. Based on these pairwise estimates of functional connectivity, we formed graphs which were then characterized in terms of local structure [local efficiency (LE)] and overall integration (global efficiency). The overall data analytic scheme was applied twice, in a static and time-varying mode. Our results showed a characteristic trend: functional segregation dominates the network organization of younger brains. Moreover, in childhood, the overall functional network possesses more prominent small-world network characteristics than in early acorrect in xmldulthood in accordance with the Neural Efficiency Hypothesis. The above trends were intensified by the time-varying approach and identified for the whole set of tested frequency bands (from delta to low gamma). By mapping the time-indexed connectivity patterns to multivariate timeseries of nodal LE measurements, we carried out an elaborate study of the functional segregation dynamics and demonstrated that the underlying network undergoes transitions between a restricted number of stable states, that can be thought of as "network-level microstates". The rate of these transitions provided a robust marker of developmental and task-induced alterations, that was found to be insensitive to reference montage and independent component analysis denoising. PMID- 26157512 TI - EEG gamma-band activity during audiovisual speech comprehension in different noise environments. AB - The presence of cross-modal stochastic resonance in different noise environments has been proved in previous behavioral and event-related potential studies, while it was still unclear whether the gamma-band oscillation study was another evidence of cross-modal stochastic resonance. The multisensory gain of gamma-band activity between the audiovisual (AV) and auditory-only conditions in different noise environments was analyzed. Videos of face motion articulating words concordant with different levels of pink noise were used as stimuli. Signal-to noise ratios (SNRs) of 0, -4, -8, -12 and -16 dB were selected to measure the speech recognition accuracy and EEG activity for 20 healthy subjects. The power and phase of EEG gamma-band oscillations increased in a time window of 50-90 ms. The multisensory gains of evoked and total activity, as well as phase-locking factor, were greatest at the -12 dB SNR, which were consistent with the behavioral result. The multisensory gain of gamma-band activity showed an inverted U-shaped curve as a function of SNR. This finding confirmed the presence of cross-modal stochastic resonance. In addition, there was a significant correlation between evoked activity and phase-locking factor of gamma-band at five different SNRs. Gamma-band oscillation was believed to play a role in the rapid processing and information linkage strengthening of AV modalities in the early stage of cognitive processes. PMID- 26157513 TI - The electrocortical modulation effects of different emotion regulation strategies. AB - The current event-related potential study investigated the modulation effects of different emotion regulation strategies on electrocortical responses. When watching negative or neutral pictures, participants were instructed to perform three tasks: cognitive reappraisal, expressive suppression and passive viewing. We found that negative pictures elicited a larger late positive potential (LPP) than neutral pictures. Moreover, processes involved in strategy also had an effect on LPP amplitude, which was indicated by a larger LPP in reappraisal compared with suppression and viewing tasks when neutral pictures were presented. After the influence of processes on LPP was excluded, results showed that reappraisal effectively decreased the emotion-enhanced LPP than suppression and viewing. The difference in regulatory effect may be determined by the underlying processing mechanism. A larger frontal-central component, N2, was observed in suppression than reappraisal and viewing, which suggested that it involved the processes focusing on behavioral response. While the larger LPP found in reappraisal implicated that it recruited cognitive processes focusing on the picture meaning. PMID- 26157514 TI - Frequency-domain order parameters for the burst and spike synchronization transitions of bursting neurons. AB - We are interested in characterization of synchronization transitions of bursting neurons in the frequency domain. Instantaneous population firing rate (IPFR) [Formula: see text], which is directly obtained from the raster plot of neural spikes, is often used as a realistic collective quantity describing population activities in both the computational and the experimental neuroscience. For the case of spiking neurons, a realistic time-domain order parameter, based on [Formula: see text], was introduced in our recent work to characterize the spike synchronization transition. Unlike the case of spiking neurons, the IPFR [Formula: see text] of bursting neurons exhibits population behaviors with both the slow bursting and the fast spiking timescales. For our aim, we decompose the IPFR [Formula: see text] into the instantaneous population bursting rate [Formula: see text] (describing the bursting behavior) and the instantaneous population spike rate [Formula: see text] (describing the spiking behavior) via frequency filtering, and extend the realistic order parameter to the case of bursting neurons. Thus, we develop the frequency-domain bursting and spiking order parameters which are just the bursting and spiking "coherence factors" [Formula: see text] and [Formula: see text] of the bursting and spiking peaks in the power spectral densities of [Formula: see text] and [Formula: see text] (i.e., "signal to noise" ratio of the spectral peak height and its relative width). Through calculation of [Formula: see text] and [Formula: see text], we obtain the bursting and spiking thresholds beyond which the burst and spike synchronizations break up, respectively. Consequently, it is shown in explicit examples that the frequency-domain bursting and spiking order parameters may be usefully used for characterization of the bursting and the spiking transitions, respectively. PMID- 26157515 TI - Coupling relationship between the central pattern generator and the cerebral cortex with time delay. AB - Brain activity is a cooperative process among neurons and involves the coupling relationship, which is crucial to perform operational tasks in various specialized areas of the nervous system. A finite signal transmission speed along the axons results in a space-dependent time delay. The central pattern generator (CPG) can in principle produce basic locomotor rhythm in the absence of inputs from higher brain centers and peripheral sensory feedback. To study the dynamic performance of CPG with time delay and its coupling relationship with the cerebral cortex, a new CPG model with time delay and a model of the neural mass model (NMM) and the CPG are developed. The coupling model is based on biological experimental results. Bifurcation theories and maximal Lyapunov exponent are used to analyze the dynamic performance. From the results, some CPGs are suggested to be embedded in limbs and composed of the parameters space which corresponds to the one of the cerebral cortex. This embodiment of humans can reduce the burden of the brain and simplify the control of the locomotion. The results also show that the phase diagram of the CPG cannot keep the limit cycle, and that the state of the NMM becomes increasingly chaotic as time delay increases. This finding implies that a person with slow reaction can easily lose the stability of his or her locomotion. PMID- 26157516 TI - Exponential synchronization for fuzzy cellular neural networks with time-varying delays and nonlinear impulsive effects. AB - In this paper, the globally exponential synchronization of delayed fuzzy cellular neural networks with nonlinear impulsive effects are concerned. By utilizing inequality techniques and Lyapunov functional method, some sufficient conditions on the exponential synchronization are obtained based on [Formula: see text] norm. Finally, a simulation example is given to illustrate the effectiveness of the theoretical results. PMID- 26157517 TI - Sufficient and necessary conditions for Lyapunov stability of genetic networks with SUM regulatory logic. AB - In this paper, a nonlinear model for genetic regulator networks (GRNs) with SUM regulatory logic is presented. Four sufficient and necessary conditions of global asymptotical stability and global exponential stability for the equilibrium point of the GRNs are proposed, respectively. Specifically, three weak sufficient conditions and corresponding corollaries are derived by using comparing theorem and Dini derivative method. Then, a famous GRN model is used as the example to illustrate the effectiveness of our theoretical results. Comparing to the results in the previous literature, some novel ideas, study methods and interesting results are explored. PMID- 26157518 TI - Lognormal distribution of firing time and rate from a single neuron? AB - Even a single neuron may be able to produce significant lognormal features in its firing statistics due to noise in the charging ion current. A mathematical scheme introduced in advanced nanotechnology is relevant for the analysis of this mechanism in the simplest case, the integrate-and-fire model with white noise in the charging ion current. PMID- 26157519 TI - Prostate-Specific Antigen (PSA) and Prostate Volume: Better Predictor of Prostate Cancer for Bosnian and Herzegovina Men. AB - BACKGROUND: The serum prostate specific antigen for the early detection and screening for prostate cancer are very common used among physicians as the best screening tool for prostate cancer. The result of prostate specific antigen levels discriminates whether or not a prostate biopsy should be performed. The lack of specificity is a limitation of PSA as tumor marker, increased PSA concentrations are found not only in patients with prostate cancer but also in patients with benign prostatic disease. The object of this study was to improve the specificity and sensitivity of prostatic cancer detection. We evaluated total PSA levels, free PSA levels and the prostate volume in asymptomatic patients which came for routine check without medical history of prostate cancer. METHODS: We received medical record of 90 patients between 50-60 years. Total and free PSA in serum was measured with the analyzer Architeckt i2000 SR. Prostate volume was determined by transrectal ultrasound. RESULTS: The ratio of total and free PSA levels to prostate volume was significantly (p < 0.001) between all three groups. It was observed that increased prostate volume correlates with increased level of total and free PSA in serum. CONCLUSION: Early studies have demonstrated the advantage of measuring prostate volume with PSA total and free levels in serum as a useful tool for early diagnosis of prostate cancer. Data from this study on 90 patients with total PSA in the range from 0,22-7,0 ng/ml confirmed the well known correlation. All three parameters total PSA, free PSA and prostate volume showed significant correlation and a useful tool in prediction of prostate cancer for Bosnia and Herzegovina men. PMID- 26157520 TI - Homocysteine Induced Cerebrovascular Dysfunction: A Link to Alzheimer's Disease Etiology. AB - A high serum level of homocysteine, known as hyperhomocystenemia (HHcy) is associated with vascular dysfunction such as altered angiogenesis and increased membrane permeability. Epidemiological studies have found associations between HHcy and Alzheimer's disease (AD) progression that eventually leads to vascular dementia (VaD). VaD is the second most common cause of dementia in people older than 65, the first being AD. VaD affects the quality of life for those suffering by drastically decreasing their cognitive function. VaD, a cerebrovascular disease, generally occurs due to cerebral ischemic events from either decreased perfusion or hemorrhagic lesions. HHcy is associated with the hallmarks of dementia such as tau phosphorylation, Abeta aggregation, neurofibrillary tangle (NFT) formation, neuroinflammation, and neurodegeneration. Previous reports also suggest HHcy may promote AD like pathology by more than one mechanism, including cerebral microangiopathy, endothelial dysfunction, oxidative stress, neurotoxicity and apoptosis. Despite the corelations presented above, the question still exists - does homocysteine have a causal connection to AD? In this review, we highlight the role of HHcy in relation to AD by discussing its neurovascular effects and amelioration with dietary supplements. Moreover, we consider the studies using animal models to unravel the connection of Hcy to AD. PMID- 26157521 TI - Quantification of Amino Acid Neurotransmitters in Cerebrospinal Fluid of Patients with Neurocysticercosis. AB - BACKGROUND: Neurocysticercosis is a parasitic disease that affects the central nervous system. Its main clinical manifestations are epileptic seizures. The objective of this study was to investigate the correlation between neurotransmitter concentrations in cerebrospinal fluid (CSF) and the different evolutive forms of neurocysticercosis with or without seizures. METHODS: Neurotransmitter concentrations (Aspartate, Glutamate, GABA, Glutamine, Glycine, Taurine) were determined in CSF samples from 42 patients with neurocysticercosis divided into patients with the active cystic form (n = 24, 12 with and 12 without seizures) and patients with calcified form (n = 18, 12 with and 6 without seizures), and a control group consisting of 59 healthy subjects. RESULTS: Alterations in amino acid concentration were observed in all patients with neurocysticercosis. CONCLUSION: We conclude that disturbances in amino acid metabolism accompany the presentation of neurocysticercosis. Replacement of the terms inactive cyst by reactive inactive cyst and calcification by reactive calcification is suggested. PMID- 26157522 TI - Application of Pain Quantitative Analysis Device for Assessment of Postoperative Pain after Arthroscopic Rotator Cuff Repair. AB - PURPOSE: The PainVisionTM system was recently developed for quantitative pain assessment. Here, we used this system to evaluate the effect of plexus brachialis block on postoperative pain after arthroscopic rotator cuff repair. METHODS: Fifty-five patients who underwent arthroscopic rotator cuff repair were included in this study. First 26 cases received no plexus brachialis block (control group), and the next 29 cases received the plexus brachialis block before surgery (block group). Patients completed the visual analog scale at 4, 8, 16, and 24 hours after surgery, and the intensity of postoperative pain was assessed with PainVisionTM at 16 hours. The postoperative use of non-steroidal anti inflammatory agents was also recorded. RESULTS: The pain intensity at 16 hours after surgery assessed by PainVisionTM was significantly lower in the block group than in the control group (block, 252.0 +/- 47.8, control, 489.0 +/- 89.1, P < 0.05). However, there were no differences in the VAS values at 16 hours between the 2 groups (block, 4.3 +/- 0.6, control, 5.7 +/- 0.4, P = N.S.). The pain intensity and VAS at 16 hours after surgery were highly correlated (r = 0.59, P = 0.006 in the block group and r = 0.62, P = 0.003 in the control group). The effect size of the assessment by PainVisionTM was bigger than that of VAS (r=0.31 in VAS and 0.51 in Pain vision). CONCLUSION: The PainVisionTM system could be useful to evaluate postoperative pain because it enables the quantification and comparison of pain intensity independent of individual pain thresholds. PMID- 26157523 TI - Arthroplasty in the Valgus Knee: Comparison and Discussion of Lateral vs Medial Parapatellar Approaches and Implant Selection. AB - Constrained implants are frequently used for primary total knee arthroplasty (TKA) in patients with moderate and severe genu-valgum (>10). This deformity presents corrective challenges for ligament release. The lateral-parapatellar approach has been advocated as an alternative to the traditional medial parapatellar approach. Claimed advantages include better access for release of tight ligamentous structures, without requirement for release of the medial collateral ligament. We present our comparative experience of the use of an unconstrained knee-replacement prosthesis inserted by the lateral-parapatellar approach in comparison to a constrained-knee prosthesis inserted via the medial parapatellar approach. 49 primary total knee-replacements in 48 (6 males, 42 females) patients were performed; 32 through a lateral-parapatellar approach (group L) using an unconstrained-prosthesis and 17 through a medial-parapatellar approach more often requiring a constrained-prosthesis (group M). Mean preoperative valgus angle was 18.5 (range 11-34). Patient demographics (p=0.7) and valgus correctability were similar between the two groups. There was no significant difference in the mean post-operative valgus angle. This was 4.2 (range 1-9.5) using the lateral-parapatellar approach and 5.3 (range 0.3-10), p=0.12, using the medial-parapatellar approach. Transient common peroneal injury occurred in 2 patients, both group L, in the presence of valgus angles of greater than 20. To date no joints have been revised, or are unstable. The use of a lateral-parapatellar approach, appropriate soft tissue release, and an unconstrained PCL-preserving implant, yielded in all cases a stable, well aligned knee arthroplasty. This represents a viable alternative to the constrained prosthesis using a medial-parapatellar approach in patients with moderate and severe genu-valgum. PMID- 26157524 TI - Ulnar Shortening Osteotomy After Distal Radius Fracture Malunion: Review of Literature. AB - Malunion of distal radius fracture is often complicated with shortening of the radius with disturbed radio- ulnar variance, frequently associated with lesions of triangular fibrocartilage complex and instability of the distal radioulnar joint. Positive ulnar variance may result in wrist pain located in ulnar part of the joint, limited ulnar deviation and forearm rotation with development of degenerative changes due to the overloading that occurs between the ulnar head and corresponding carpus. Ulnar shortening osteotomy (USO) is the standard procedure for correcting positive ulnar variance. Goal of this procedure is to minimize the symptoms by restoring the neutral radio - ulnar variance. In this paper we present a variety of surgical techniques available for ulnar shorthening osteotomy, their advantages and drawbacks. Methods of ulnar shortening osteotomies are divided into intraarticular and extraarticular. Intraarticular method of ulnar shortening can be performed arthroscopically or through open approach. Extraarticular methods include subcapital osteotomy and osteotomy of ulnar diaphysis, which depending on shape can be transverse, oblique, and step cut. All of those osteotomies can be performed along wrist arthroscopy in order to dispose and treat possibly existing triangular fibrocartilage complex injuries. At the end we described surgical procedures that can be done in case of ulnar shorthening osteotomy failure. PMID- 26157525 TI - Efficacy of Percutaneous Vertebroplasty in the Treatment of Osteoporotic Vertebral Compression Fractures with Intravertebral Cleft. AB - Intravertebral cleft (IVC) is frequently observed in patients with painful osteoporotic vertebral compression fracture (OVCF). Some studies reported the usefulness of percutaneous vertebroplasty (PVP) for treating OVCF with IVC. However, systematic studies are scarce, and their results are conflicting. The purpose of this study was to evaluate the clinical and radiographic results of PVP in the treatment of painful OVCF with IVC. Two hundred ninety-one patients with OVCF with IVC underwent PVP. Back pain was measured using a visual analog scale (VAS), and physical disability was assessed using the Oswestry Disability Index (ODI). Three radiological parameters were assessed: the local kyphotic angle, percentage spinal canal cross-sectional area of compromise, and intravertebral instability of the affected vertebra. The mean follow-up period was 28 months. The mean values for the VAS and ODI were 8.4 and 60.0%, respectively, before PVP, versus 3.9 and 35.4%, respectively, at the final follow up. The average local kyphotic angle, percentage spinal canal cross-sectional area of compromise, and intravertebral instability were 10.5 degrees , 17.9% and 6.1 degrees , respectively, before PVP and 8.1 degrees , 15.2%, and 0.8 degrees , respectively, at the final follow-up. There were no neurological or systemic complications due to cement leakage. PVP is an effective and safe intervention for treating OVCF with IVC. PMID- 26157526 TI - Excellent Functionality Despite Clinico-Radiological Deformity in Osteomyelitis Variolosa - A Case Report. AB - Despite the eradication of smallpox from the world in 1980 the osteo-articular sequelae of smallpox are still occasionally noticed in previously endemic areas. The sequelae of osteomyelitis variolosa may raise a diagnostic challenge to the untrained eyes of the surgeon. We present a case of "osteomyelitis variolosa" in a 70 years old patient. The patient had bilateral dislocation of the elbow joint with multidirectional instability. There was distortion of the articular surfaces and ankylosis of the bilateral proximal radio-ulnar joint. Hypoplasia of the right ulna with short fourth and fifth metacarpals of the left hand and hypoplasia of right fourth metacarpal with cortical thickening was noted radiologically. The patient had minimal disability of his elbows despite the striking radiological abnormality and was functionally independent. PMID- 26157527 TI - Significant Efficacy of Tramadol/Acetaminophen in Elderly Patients with Chronic Low Back Pain Uncontrolled by NSAIDs: An Observational Study. AB - Chronic low back pain (LBP) is a common condition and is generally treated using non-steroidal anti-inflammatory drug (NSAID); however, chronic NSAID use can decrease renal function. Tramadol, a weak opioid agonist, may improve chronic LBP and disability, while avoiding adverse effects such as gastrointestinal and renal toxicity. However, few studies have evaluated the short-term efficacy of opioids in Asian patients with chronic LBP. In this study, 24 patients with chronic LBP unresponsive to NSAIDs (10 men, 14 women; mean age, 65.1 +/- 12.1 years) were prescribed tramadol/acetaminophen (37.5 mg/325 mg; four tablets daily) for 1 month. Then, the following parameters were assessed at baseline and after 1 week and 1 month of treatment: leg pain and LBP (Visual Analog Score [VAS]); activity of daily life (Roland-Morris Disability Questionnaire [RDQ]); and disability (Oswestry Disability Index [ODI]). Leg pain resolved within 1 week (p = 0.00093); however, LBP was relieved only at 1 month (p = 0.00034). The mean RDQ (p = 0.015) and ODI (p = 0.0032) scores were improved at 1 month. A total 41.6% of patients reported nausea and floating sensation beginning tramadol/acetaminophen treatment, and 12.5% (four patients) discontinued treatment as a result. LBP did not improve in 25% of patients administered tramadol/acetaminophen. Because this was an observational study, rather than a comparative study, further investigation is needed to evaluate the long-term efficacy of tramadol/acetaminophen in elderly patients with chronic LBP unresponsive to NSAIDs. PMID- 26157528 TI - A New Case of Fracture of a Modular Femoral Neck Device After a Total Hip Arthroplasty. AB - This report addresses a new case of a modular femoral neck fracture after total hip arthroplasty. A now seventy-three-year- old overweight female underwent total hip replacement of the right hip because of osteoarthritis in the year 2002. Then, years later, the head and the polyethylene were changed due to wear. In October 2014, the patient was transferred from the trauma department of her hometown to our department after she had slipped and fallen directly on her right hip. The x-rays done at the trauma department have shown no periprosthetic fracture but a fracture of the modular neck. Therefore, the patient was transferred to our department in order to undergo a revision arthroplasty with change of the stem and head after splitting the femur. PMID- 26157529 TI - Assessment of Dosing and Patient Factors on the Efficacy of Warfarin Following Total Joint Replacement. AB - The purpose of this study was to determine the percentage of patients discharged with a subtherapeutic INR <1.8 using our institutions inpatient warfarin dosing nomogram following total joint arthroplasty (TJA). We examined predisposing risk factors for a subtherapeutic discharge (INR <1.8), including increased body weight, age, gender, end stage renal disease (ESRD), smoking, and peri-operative transfusion. Chart review identified 249 patients for study inclusion. Logistic regression (LR) was used to identify associated risk factors for a subtherapeutic INR (<1.8) on day of discharge. The majority of patients (58.6%, 146 of 249) following TJA surgery were found to have a subtherapeutic INR level (INR<1.8) at discharge (mean length of stay 2.6 days). Multivariate LR analysis found that weight greater than 180 lbs. (OR 2.08, CI 1.09, 3.98, P=0.027) was found to increase the odds of a subtherapeutic INR on day of discharge. Our results were not significant for weight 20% beyond ideal body weight, age (>65y), gender, peri operative transfusion, smoking, ESRD or autoimmune disease. A patient's body weight influences response to warfarin following TJA. An inpatient warfarin dosing nomogram that takes into account a patient's weight should be used to reduce the risk of subtherapeutic INR levels in obese TJA patients. PMID- 26157530 TI - Complications and Predictors of Need for Return to the Operating Room in the Treatment of Supracondylar Humerus Fractures in Children. AB - Supracondylar humerus fractures are common pediatric injuries. Little is known about the risk factors for repeat operative procedures. A retrospective chart review of 709 patients treated for a displaced supracondylar humerus fracture was performed to identify risk factors for return to the operating room during the initial post-operative period. Deviations of routine fracture care were recorded and complication rates were compared between Gartland type 2 and 3 fractures using logistic regression. Type 3 fractures were found to have a higher complication rate, and, specifically, more peri-operative nerve palsies, more likely to need to return to the operating room for hardware removal, to lose fracture reduction, and require a return to the operating room for any reason. Five risk factors which may require returning to the operating room were identified: younger patient age, left sided fractures, type 3 fractures, peri operative nerve palsy, and post-operative infection. In conclusion, Gartland type 3 supracondylar humerus fractures are associated with more complications then type 2 fractures. Risk factors for the need to return to the operating room in the post-operative period include: younger patient age, left sided fractures, type 3 fractures, peri-operative nerve palsy, and post-operative infection. Patients with these risk factors should be considered at risk for return to the OR and fracture fixation and follow up protocols should be adjusted for this risk. LEVEL OF EVIDENCE: Prognostic Study, Level II. PMID- 26157531 TI - Meniscal Scaffolds - Preclinical Evidence to Support their Use: A Systematic Review. AB - Arthroscopic meniscal treatment is the most common procedure performed in the orthopedic practice. Current management of meniscal pathology relies on different therapeutic options, ranging from selective meniscectomy, suturing, and to meniscal replacement by using either allografts or scaffolds. The progresses made in the field of regenerative medicine and biomaterials allowed to develop several meniscal substitutes, some of those currently used in the clinical practice. Before reaching the clinical application, these devices necessarily undergo accurate testing in the animal model: the aim of the present manuscript is to systematically review the scientific evidence derived by animal model results for the use of meniscal scaffolds, in order to understand the current state of research in this particular field and to identify the trends at preclinical level that may influence in the near future the clinical practice. Thirty-four papers were included in the present analysis. In 12 cases the meniscal scaffolds were used with cells to further stimulate tissue regeneration. With the exception of some negative reports regarding dacron-based scaffolds, the majority of the trials highlighted that biomaterials and bio-engineered scaffolds are safe and could play a beneficial role in stimulating meniscal healing and in chondral protection. With regard to the benefits of cell augmentation, the evidence is limited to a small number of studies and no conclusive evidence is available. However, preclinical evidence seems to suggest that cells could enhance tissue regeneration with respect to the use of biomaterials alone, and further research should confirm the translational potential of cell-based approach. PMID- 26157532 TI - Lower Dislocation Rate Following Total Hip Arthroplasty via Direct Anterior Approach than via Posterior Approach: Five-Year-Average Follow-Up Results. AB - OBJECTIVE: The aim of the study was to compare the dislocation rate between total hip arthroplasty (THA) via direct anterior approach (DAA) and via posterior approach (PA). METHODS: We compared a consecutive series of 139 THAs via DAA with 177 THAs via PA. All study patients received ceramic-on-ceramic bearing surfaces and similar uncemented prostheses. Dislocation-free survival after THA was estimated using the Kaplan-Meier survival method and compared between groups using the log-rank test. RESULTS: In the DAA group, none of 139 hips experienced dislocations in five-year-average follow-up. In the PA group, seven hips experienced dislocations among 177 hips (4 %). The dislocation was significantly less in the DAA group compared to the PA group (p = 0.033). CONCLUSION: The dislocation rate of THA via DAA was significantly less than that of THA via PA. PMID- 26157533 TI - 10-Year Survival of Acetabular Reinforcement Rings/Cages for Complex Hip Arthroplasty. AB - INTRODUCTION: Acetabular reinforcement rings/ cages (AR) are commonly used for reconstruction of bone defects in complex hip arthroplasty. The aim of this study was to retrospectively investigate the 10-year survival rate of Ganz reinforcement rings and Burch-Schneider cages used in a single institution. MATERIAL AND METHODS: Between September 1999 and June 2002 all ARs, implanted in one institution, were identified. All patients had regular clinical and radiographic follow-up and were included in this study. Their prospectively collected clinical and radiographic data was retrospectively analyzed. In case of death before the 10-year follow-up examination, patient's families or their general practitioner was contacted by telephone. The main outcome measures were survival of the ARs and kind of revision surgery. RESULTS: The 10-year survival rate was 77.7%. At 10-year follow-up, 5/60 (8,3%) patients could not be located and had to be excluded therefore. 27/55 (49,1%) were dead, whereof 22 had no revision of the ARs before death (after a mean of 66 months; range: 0 - 123). Of the remaining 28/55 (50,9%) patients, 23 patients (24 ARs) had no revision of the ARs. CONCLUSION: Despite the high mortality rate of this study's collective, ARs for complex primary or revision total hip arthroplasty provided predictable long term results. LEVEL OF EVIDENCE: Clinical investigation. PMID- 26157534 TI - Evaluation of an Image-Based Tool to Examine the Effect of Fracture Alignment and Joint Congruency on Outcomes after Wrist Fracture. AB - Some mal-alignment of the wrist occurs in up to 71% of patients following a distal radius fracture. A multiple case study was used to provide proof of principle of an image-based technique to investigate the evolution and impact of post-traumatic joint changes at the distal radioulnar joint. Participants who had a unilateral distal radius fracture who previously participated in a prospective study were recruited from a single tertiary hand center. Long term follow-up measures of pain, disability, range of motion and radiographic alignment were obtained and compared to joint congruency measures. The inter-bone distance, a measure of joint congruency was quantified from reconstructed CT bone models of the distal radius and ulna and the clinical outcome was quantified using the patient rated wrist evaluation. In all four cases, acceptable post-reduction alignment and minimal pain/disability at 1-year suggested good clinical outcomes. However, 10 years following injury, 3 out of 4 patients had radiographic signs of degenerative changes occurring in their injured wrist (distal radioulnar joint/radio-carpal joint). Proximity maps displaying inter-bone distances showed asymmetrical congruency between wrists in these three patients. The 10-year PRWE (patient rated wrist evaluation) varied from 4 to 60, with 3 reporting minimal pain/disability and one experiencing high pain/disability. These illustrative cases demonstrate long-term joint damage post-fracture is common and occurs despite positive short-term clinical outcomes. Imaging and functional outcomes are not necessarily correlated. A novel congruency measure provides an indicator of the overall impact of joint mal-alignment that can be used to determine predictors of post-traumatic arthritis and is viable for clinical or large cohort studies. PMID- 26157535 TI - Effect of Osteonecrosis Intervention Rod Versus Core Decompression Using Multiple Small Drill Holes on Early Stages of Necrosis of the Femoral Head: A Prospective Study on a Series of 60 Patients with a Minimum 1-Year-Follow-Up. AB - INTRODUCTION: The conventional CD used 10 mm drill holes associated with a lack of structural support. Thus, alternative methods such as a tantalum implant, small drill holes, and biological treatment were developed to prevent deterioration of the joint. The treatment of CD by multiple 3.2 mm drill holes could reduce the femoral neck fracture and partial weight bearing was allowed. This study was aimed to evaluate the effect of osteonecrosis intervention rod versus core decompression using multiple small drill holes on early stages of necrosis of the femoral head. METHOD: From January 2011 to January 2012, 60 patients undergoing surgery for osteonecrosis with core decompression were randomly assigned into 2 groups based on the type of core decompression used: (1) a total of 30 osteonecrosis patients (with 16 hips on Steinburg stageI,20 hips on Steinburg stageII) were treated with a porous tantalum rod insertion. The diameter of the drill hole for the intervention rod was 10mm.(2) a total of 30 osteonecrosis patients (with 14 hips on Steinburg stageI,20 hips on Steinburg stageII) were treated with core decompression using five drill holes on the lateral femur, the diameter of the hole was 3.2 mm. The average age of the patient was 32.6 years (20-45 years) and the average time of follow-up was 25.6 months (12- 28 months) in the rod implanted group. The average age of the patient was 35.2 years (22- 43 years) and the average time of follow-up was 26.3 months (12-28 months) in the small drill holes group. RESULTS: The average of surgical time was 40 min, and the mean volume of blood loss was 30 ml in both surgical groups. The average of Harris score was improved from 56.2 +/- 7.1 preoperative to 80.2 +/- 11.4 at the last follow-up in the rod implanted group (p < 0.05). The mean Harris score was improved from 53.8 +/- 6.6 preoperative to 79.7 +/- 13.2 at the last follow-up in the small drill holes group (p<0. 05). No significant difference was observed in Harris score between the two groups. At the last follow-up, 28 of 36 hips were at the same radiographic stages as pre-operation, and 8 deteriorated in the rod implanted group. 26 of 34 hips were at the same radiographic stage as pre-operation, and 8 deteriorated in the small drill holes group. No significant difference was observed in radiographic stage between the two groups. There was no favourable result on the outcome of a tantalum intervention implant compared to multiple small drill holes. DISCUSSION: CD via multiple small drill holes would allow similar postoperative load-bearing and seems to result in similar or even better clinical outcome without the prolonged implantation of an expensive tantalum implant. A tantalum rod intervention and core decompression using multiple small drill holes were effective on the stage I hips rather than stage II hips. PMID- 26157536 TI - Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. AB - Treatment-emergent mutations and drug resistance were analyzed in virus from HIV infected children meeting virologic failure (VF) criteria over 48 weeks following treatment with unboosted fosamprenavir or fosamprenavir/ritonavir-containing regimens in studies APV20002 and APV29005. Both antiretroviral therapy (ART) naive and ART-experienced patients were enrolled. Patients met VF criteria by either failing to suppress HIV-RNA to <400 copies/mL through week 24 or after confirmed viral rebound (>=400 copies/mL) anytime through week 48. Viral isolates were analyzed for treatment-emergent mutations or reduced drug susceptibility. Through week 48, 25/109 (23%) of APV29005 and 9/54 (17%) APV20002 study patients met VF. VF was more common in ART-experienced patients (68% and 78%, respectively). Major or minor treatment-emergent mutations were detected at VF in virus from 3 patients receiving unboosted fosamprenavir-containing regimens and in virus from 10 patients receiving fosamprenavir/ritonavir-containing regimens across the two studies. Major protease inhibitor mutations and the reverse transcriptase mutation M184V were detected at VF in virus from 4 and 5 patients, respectively, across both studies. Reduced drug susceptibility to any drug emerged in virus from 9 patients at VF, although reduced fosamprenavir susceptibility emerged in virus from only 4 patients (2 ART-naive and 2 ART experienced). No cross-resistance to the protease inhibitor darunavir was observed. In conclusion, given the high proportion of ART-experienced children (71%) in these two studies, the overall incidence of children meeting VF criteria through 48 weeks was relatively low (21%) and development of fosamprenavir reduced drug susceptibility at VF was uncommon, further supporting the use of fosamprenavir-containing ART regimens in HIV-infected children. PMID- 26157537 TI - Factors Supporting and Inhibiting Adherence to HIV Medication Regimen in Women: A Qualitative Analysis of Patient Interviews. AB - Adherence to antiretroviral therapy reduces morbidity and mortality; however rates of non-adherence are variable among women for unclear reasons. This study was a single-center qualitative analysis of interviews with 18 female HIV positive non-adherent patients (defined by virologic failure) to explore psychosocial factors impacting adherence. Factors identified were categorized as promoting, inhibiting or having no effect on adherence. Three themes, characterized as social factors, illness factors and other societal pressures, were identified. Medical systems support, family support and compliance for children were most commonly identified as promoting adherence, while psychiatric comorbidities, lack of medical systems support and side effects were identified most often as inhibitors of adherence. While stigma was frequently identified, it was not seen as a barrier to adherence. Enhancing relationships between patients and their providers as well as their community support systems are critical avenues to pursue in improving compliance. Interventions to promote compliance are important avenues of future research. PMID- 26157539 TI - The Continuation of Care. PMID- 26157538 TI - Outcomes of Triplets reduced to Twins versus non-reduced Triplet Pregnancies. AB - INTRODUCTION: This study examined the outcomes of triplet pregnancies selectively reduced to twin pregnancies, compared with non-reduced triplet pregnancies using a standardized approach. MATERIAL AND METHODS: This study is an observational retrospective study of all women who presented to the Fetal Diagnostic Center between 1999-2009, had triplet pregnancies in the first trimester, received prenatal care and delivered at Abington Memorial Hospital. Data analysis was performed with SPPS version 15 for Windows using analysis of variance and Fisher's Exact test. RESULTS: 132 triplet pregnancies were identified. In the reduced group (n = 30) compared to the non-reduced triplet group (n = 102) average gestational age of delivery was longer 34.6 weeks versus 31.2 weeks gestation (P = <0.0005) and days in hospital were less 9.0 versus 26.7 days (P = .001). There was a significantly lower incidence of gestational diabetes and preterm labor in reduced pregnancies. Rate of loss, defined as delivery less than 24 weeks, were similar [3.3% versus 4.9%]. DISCUSSION: Women electing to reduce a triplet pregnancy to twins have higher gestational ages at delivery, lower rates of gestational diabetes and preterm labor, and spent fewer days in hospital than non-reduced triplet pregnancies. PMID- 26157541 TI - Oncology Innovation and Challenging Choices: Balancing Value and Funding Priorities in Light of an Abundance of New Treatment Options. PMID- 26157540 TI - Treatment Sequences and Pharmacy Costs of 2 New Therapies for Metastatic Castration-Resistant Prostate Cancer. AB - BACKGROUND: The approval of new therapies for metastatic castration-resistant prostate cancer (mCRPC), including the oral agents abiraterone acetate and enzalutamide, has altered the standard of care for patients with mCRPC. Little information exists regarding the sequences in which new therapies for mCRPC with evidence of survival benefits are used. OBJECTIVE: To describe the sequence of medication use for patients with mCRPC as observed in 3 healthcare data sets. METHODS: Three healthcare claims data sets were used to identify patients with mCRPC who had no previous use of and were newly initiating 1 of the 2 oral study drugs (ie, abiraterone acetate or enzalutamide). The index date was the first study drug claim after September 1, 2012. Patients were followed until the data cutoff or until being lost to follow-up. Descriptive statistics summarized the proportion of patients receiving 1 line of therapy versus >=2 lines of therapy. The use of a corticosteroid and the mean monthly pharmacy costs of abiraterone acetate or enzalutamide during the follow-up period were compared between the cohorts. RESULTS: A total of 3525 patients with mCRPC were identified from data set 1, 499 patients from data set 2, and 1949 patients from data set 3. The first line use of abiraterone acetate was observed in 74%, 82%, and 80% of data sets 1, 2, and 3, respectively, and the first-line use of enzalutamide was seen in 26%, 18%, and 20%, respectively, of these same populations. The concomitant use of corticosteroids was observed in patients receiving first-line abiraterone acetate and in patients receiving first-line enzalutamide in all 3 data sets. After September 2012, abiraterone acetate was the most frequently administered therapy for mCRPC among the 2 oral agents, abiraterone acetate and enzalutamide. The monthly pharmacy costs associated with abiraterone acetate were significantly lower than those associated with enzalutamide in all 3 data sets. CONCLUSIONS: Based on the data used in this study, abiraterone acetate was more frequently administered for patients with mCRPC than enzalutamide. The concomitant use of corticosteroids was common in patients receiving first-line abiraterone acetate or first-line enzalutamide therapy. Patients receiving abiraterone acetate had significantly lower monthly pharmacy costs than patients receiving enzalutamide. These findings may facilitate the estimation of the budgetary impact of a treatment mix for population health and for managed care stakeholders. PMID- 26157543 TI - The 2015 Oncology Drug Pipeline: Innovation Drives the Race to Cure Cancer. PMID- 26157542 TI - Estimating the Costs of Therapy in Patients with Relapsed and/or Refractory Multiple Myeloma: A Model Framework. AB - BACKGROUND: Multiple myeloma is a progressive cancer for which there is no cure. Despite treatment, almost all patients eventually experience periods of disease relapse and remission. With the increasing use of novel therapies, including bortezomib, lenalidomide, carfilzomib, pomalidomide, and panobinostat, benchmarks for assessing the value of these therapies in treating patients with relapsed or refractory multiple myeloma (RRMM) are needed for physicians and payers alike. OBJECTIVES: To develop a model framework and to calculate an annual estimate of the total costs per patient for the treatment of patients with RRMM using 7 common treatment regimens, including bortezomib plus dexamethasone; panobinostat, bortezomib, and dexamethasone; lenalidomide plus dexamethasone; lenalidomide, bortezomib, and dexamethasone; carfilzomib; carfilzomib, lenalidomide, and dexamethasone; and pomalidomide plus dexamethasone. METHODS: The expenditures for drugs and their administration, for prophylaxis and adverse event monitoring, and for the treatment of grade 3 or 4 adverse events were included in the calculations of the total pharmacy and medical costs. The drug costs were based on published pricing and labeled dosing schedules; the adverse event prophylaxis and monitoring costs were obtained from peer-reviewed publications; and the adverse event incidence rates were obtained from each regimen's prescribing information and from clinical trials. All the costs were summed over the duration of therapy for which the drugs were administered and were calculated separately for commercial and Medicare plans. The duration of therapy for each regimen was the time for which a patient had to be receiving the regimen to obtain 12 months of progression-free survival based on the duration-of-therapy to progression-free survival ratio observed from published clinical trials and/or the drug's labeling. RESULTS: The pharmacy costs were highest for pomalidomide plus dexamethasone, whereas the medical costs were highest for the combination of carfilzomib, lenalidomide, and dexamethasone. The total cost associated with available treatments for RRMM was highest for regimens that included lenalidomide (approximate range, $126,000-$256,000). Only bortezomib plus dexamethasone and the combination of panobinostat, bortezomib, and dexamethasone had total costs that were lower than $125,000 per patient. CONCLUSION: This study represents the first model developed to comprehensively estimate the costs of managing RRMM with all currently approved and guideline-recommended regimens in the United States. As such, it provides the framework and basis for further budget impact analyses and for cost-effectiveness comparisons with these regimens. PMID- 26157544 TI - Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia. AB - Herein, we report the structure-activity relationship of a novel series of (2(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-yl(aryl)methanones as potent, selective, and orally bioavailable metabotropic glutamate receptor subtype 5 (mGlu5) positive allosteric modulators (PAMs). On the basis of its robust in vitro potency and in vivo efficacy in multiple preclinical models of multiple domains of schizophrenia, coupled with a good DMPK profile and an acceptable therapeutic window, 17a (VU0409551/JNJ-46778212) was selected as a candidate for further development. PMID- 26157546 TI - An Aminopropyl Carbazole Derivative Induces Neurogenesis by Increasing Final Cell Division in Neural Stem Cells. AB - P7C3 and its derivatives, 1-(3,6-dibromo-9H-carbazol-9-yl)-3-(p-tolylamino)propan 2-ol (1) and N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-hydroxypropyl)-N-(3 methoxyphenyl)-4-methylbenzenesulfonamide (2), were previously reported to increase neurogenesis in rat neural stem cells (NSCs). Although P7C3 is known to increase neurogenesis by protecting newborn neurons, it is not known whether its derivatives also have protective effects to increase neurogenesis. In the current study, we examined how 1 induces neurogenesis. The treatment of 1 in NSCs increased numbers of cells in the absence of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), while not affecting those in the presence of growth factors. Compound 1 did not induce astrocytogenesis during NSC differentiation. 5-Bromo-2'-deoxyuridine (BrdU) pulsing experiments showed that 1 significantly enhanced BrdU-positive neurons. Taken together, our data suggest that 1 promotes neurogenesis by the induction of final cell division during NSC differentiation. PMID- 26157547 TI - Induction of Resistance to BRAF Inhibitor Is Associated with the Inability of Spry2 to Inhibit BRAF-V600E Activity in BRAF Mutant Cells. AB - The clinical benefits of oncogenic BRAF inhibitor therapies are limited by the emergence of drug resistance. In this study, we investigated the role of a negative regulator of the MAPK pathway, Spry2, in acquired resistance using BRAF inhibitor-resistant derivatives of the BRAF-V600E melanoma (A375P/Mdr). Real-time RT-PCR analysis indicated that the expression of Spry2 was higher in A375P cells harboring the BRAF V600E mutation compared with wild-type BRAF-bearing cells (SK MEL-2) that are resistant to BRAF inhibitors. This result suggests the ability of BRAF V600E to evade feedback suppression in cell lines with BRAF V600E mutations despite high Spry2 expression. Most interestingly, Spry2 exhibited strongly reduced expression in A375P/Mdr cells with acquired resistance to BRAF inhibitors. Furthermore, the overexpression of Spry2 partially restored sensitivity to the BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P cells, indicating that negative feedback including Spry2 may be bypassed in BRAF mutant melanoma cells. In addition, the siRNA-mediated knockdown of Raf-1 attenuated the rebound activation of ERK stimulated by PLX4720 in A375P cells, strongly suggesting the positive role of Raf-1 kinase in ERK activation in response to BRAF inhibition. Taken together, these data suggest that RAF signaling may be released from negative feedback inhibition through interacting with Spry2, leading to ERK rebound and, consequently, the induction of acquired resistance to BRAF inhibitors. PMID- 26157545 TI - Phosphorylation and Reorganization of Keratin Networks: Implications for Carcinogenesis and Epithelial Mesenchymal Transition. AB - Metastasis is one of hallmarks of cancer and a major cause of cancer death. Combatting metastasis is highly challenging. To overcome these difficulties, researchers have focused on physical properties of metastatic cancer cells. Metastatic cancer cells from patients are softer than benign cancer or normal cells. Changes of viscoelasticity of cancer cells are related to the keratin network. Unexpectedly, keratin network is dynamic and regulation of keratin network is important to the metastasis of cancer. Keratin is composed of heteropolymer of type I and II. Keratin connects from the plasma membrane to nucleus. Several proteins including kinases, and protein phosphatases bind to keratin intermediate filaments. Several endogenous compounds or toxic compounds induce phosphorylation and reorganization of keratin network in cancer cells, leading to increased migration. Continuous phosphorylation of keratin results in loss of keratin, which is one of the features of epithelial mesenchymal transition (EMT). Therefore, several proteins involved in phosphorylation and reorganization of keratin also have a role in EMT. It is likely that compounds controlling phosphorylation and reorganization of keratin are potential candidates for combating EMT and metastasis. PMID- 26157548 TI - Autophagy Regulates Formation of Primary Cilia in Mefloquine-Treated Cells. AB - Primary cilia have critical roles in coordinating multiple cellular signaling pathways. Dysregulation of primary cilia is implicated in various ciliopathies. To identify specific regulators of autophagy, we screened chemical libraries and identified mefloquine, an anti-malaria medicine, as a potent regulator of primary cilia in human retinal pigmented epithelial (RPE) cells. Not only ciliated cells but also primary cilium length was increased in mefloquine-treated RPE cells. Treatment with mefloquine strongly induced the elongation of primary cilia by blocking disassembly of primary cilium. In addition, we found that autophagy was increased in mefloquine-treated cells by enhancing autophagic flux. Both chemical and genetic inhibition of autophagy suppressed ciliogenesis in mefloquine-treated RPE cells. Taken together, these results suggest that autophagy induced by mefloquine positively regulates the elongation of primary cilia in RPE cells. PMID- 26157549 TI - Chitin from Cuttlebone Activates Inflammatory Cells to Enhance the Cell Migration. AB - Our previous report showed that the extract from cuttlebone (CB) had wound healing effect in burned lesion of rat and the extract was identified as chitin by HPLS analysis. We herein investigated the morphology in CB extract using scanning electron microscope (SEM). Chitin was used as a control. There is no difference in morphology between CB extract and chitin. We also assessed the role of CB extract on the production of inflammatory mediators using murine macrophages and the migration of inflammatory cells. The extract induced the production of nitric oxide (NO) in macrophages. While the extract of CB itself stimulated macrophages to increase the expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, CB extract suppressed the production of those cytokines by LPS. CB extract also induced the production of mouse IL-8 which is related to the cell migration, and treatment with CB enhanced fibroblast migration and invasion. Therefore, our results suggest that CB activates inflammatory cells to enhance the cell migration. PMID- 26157550 TI - Anti-Proliferative Effect of Naringenin through p38-Dependent Downregulation of Cyclin D1 in Human Colorectal Cancer Cells. AB - Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells. PMID- 26157551 TI - Anti-Influenza Activity of Betulinic Acid from Zizyphus jujuba on Influenza A/PR/8 Virus. AB - Betulinic acid, a pentacyclic triterpene isolated from Jujube tree (Zizyphus jujuba Mill), has been known for a wide range of biological and medicinal properties such as antibacterial, antimalarial, anti-inflammatory, antihelmintic, antinociceptive, and anticancer activities. In the study, we investigated the antiviral activity on influenza A/PR/8 virus infected A549 human lung adenocarcinoma epithelial cell line and C57BL/6 mice. Betulinic acid showed the anti-influenza viral activity at a concentration of 50 MUM without a significant cytotoxicity in influenza A/PR/8 virus infected A549 cells. Also, betulinic acid significantly attenuated pulmonary pathology including increased necrosis, numbers of inflammatory cells and pulmonary edema induced by influenza A/PR/8 virus infection compared with vehicle- or oseltamivir-treated mice in vivo model. The down-regulation of IFN-gamma level, which is critical for innate and adaptive immunity in viral infection, after treating of betulinic acid in mouse lung. Based on the obtained results, it is suggested that betulinic acid can be the potential therapeutic agent for virus infection via anti-inflammatory activity. PMID- 26157552 TI - The Pharmacological Effects of Benachio-F((r)) on Rat Gastrointestinal Functions. AB - Functional dyspepsia (FD) is a prevalent idiopathic upper gastrointestinal (GI) disorder characterized by diverse symptomatology including epigastric pain or discomfort, postprandial fullness, and early satiety. Although its pathophysiological mechanisms have not yet been fully established, the available studies suggest that the etiology of FD is invariably multifactorial. Benachio F((r)) (BF) is a proprietary liquid formulation of 7 herbal extracts that has been proposed to address this multifactorial etiology using multi-drug phytotherapy. The pharmacological effects of BF, in comparison with those of two other herbal products (Whalmyungsu((r)); WM and Iberogast((r)); IB) were evaluated in rats. In a laparotomy-induced rat model of delayed GI transit, BF significantly accelerated the delayed gastric emptying caused by morphine, apomorphine, and cisplatin, and also significantly increased mean gastric transit, as compared to the control animals. BF markedly increased gastric accommodation in rats and produced higher gastric volume values than did the control treatment. The effects of BF were generally comparable or superior to those of WM and IB in these models. Furthermore, BF significantly stimulated biliary flow, as compared to the control treatment. These results indicated that BF might have great potential as an effective phytotherapeutic agent capable of reducing GI symptoms and increasing quality of life in FD patients. PMID- 26157553 TI - Isorhamnetin Protects Human Keratinocytes against Ultraviolet B-Induced Cell Damage. AB - Isorhamnetin (3-methylquercetin) is a flavonoid derived from the fruits of certain medicinal plants. This study investigated the photoprotective properties of isorhamnetin against cell damage and apoptosis resulting from excessive ultraviolet (UV) B exposure in human HaCaT keratinocytes. Isorhamnetin eliminated UVB-induced intracellular reactive oxygen species (ROS) and attenuated the oxidative modification of DNA, lipids, and proteins in response to UVB radiation. Moreover, isorhamnetin repressed UVB-facilitated programmed cell death in the keratinocytes, as evidenced by a reduction in apoptotic body formation, and nuclear fragmentation. Additionally, isorhamnetin suppressed the ability of UVB light to trigger mitochondrial dysfunction. Taken together, these results indicate that isorhamnetin has the potential to protect human keratinocytes against UVB-induced cell damage and death. PMID- 26157554 TI - Pro-Apoptotic Activity of 4-Isopropyl-2-(1-Phenylethyl) Aniline Isolated from Cordyceps bassiana. AB - Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4 isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent. PMID- 26157555 TI - Effects of Resveratrol Supplementation on Oxidative Damage and Lipid Peroxidation Induced by Strenuous Exercise in Rats. AB - The purpose of the present study was to investigate the effects of resveratrol supplementation on oxidative damage and lipid peroxidation induced by strenuous exercise in rats. The rats were randomly divided into five groups: a sedentary control group, an exercise control group, and three treatment exercise groups administered increasing doses of resveratrol (25, 50, and 100 mg/kg body weight). Resveratrol was administered by oral gavage once daily for four weeks. At the end of the four-week period, the rats performed a strenuous exercise on the treadmill, and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2' deoxyguanosine (8-OHdG) were measured. The results showed that resveratrol supplementation had protective effects against strenuous exercise-induced oxidative damage and lipid peroxidation by lowering the levels of LDH, CK, MDA, 4 HNE, and 8-OHdG in the serum or muscle of rats. These beneficial effects are probably owing to the inherent antioxidant activities of resveratrol. PMID- 26157556 TI - Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE(TM). AB - The eye irritation potential of drug candidates or pharmaceutical ingredients should be evaluated if there is a possibility of ocular exposure. Traditionally, the ocular irritation has been evaluated by the rabbit Draize test. However, rabbit eyes are more sensitive to irritants than human eyes, therefore substantial level of false positives are unavoidable. To resolve this species difference, several three-dimensional human corneal epithelial (HCE) models have been developed as alternative eye irritation test methods. Recently, we introduced a new HCE model, MCTT HCE(TM) which is reconstructed with non transformed human corneal cells from limbal tissues. Here, we examined if MCTT HCE(TM) can be employed to evaluate eye irritation potential of solid substances. Through optimization of washing method and exposure time, treatment time was established as 10 min and washing procedure was set up as 4 times of washing with 10 mL of PBS and shaking in 30 mL of PBS in a beaker. With the established eye irritation test protocol, 11 solid substances (5 non-irritants, 6 irritants) were evaluated which demonstrated an excellent predictive capacity (100% accuracy, 100% specificity and 100% sensitivity). We also compared the performance of our test method with rabbit Draize test results and in vitro cytotoxicity test with 2D human corneal epithelial cell lines. PMID- 26157557 TI - Cardiovascular Safety Pharmacology of Sibutramine. AB - Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 MUM in patch clamp assay and increased the heart rate and blood pressure (76 Deltabpm in heart rate and 51 DeltammHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 MUM and 30 MUM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation. PMID- 26157558 TI - Correlation between Aerobic Fitness and Body Composition in Middle School Students. AB - BACKGROUND: Since correlations have been found between body composition and physical activity in different parts of the world, inactivity and poor physical condition likely contributes main factors in childhood obesity. This study was implemented to determine the relationship between cardiovascular fitness and body composition in a group of Iranian middle school students. METHODS: In this descriptive study, subjects comprised of 12,946 students (10,531 girls and 2,415 boys aged 11-13 years) in the city of Isfahan. Height, weight, body-fat percent, body mass index, and cardiovascular fitness of the aforesaid students were measured by valid tests. RESULTS: This study showed that fat percentage and aerobic fitness (VO2 max) of girls were 24.73%, and 29.5 (ml/kg/min) and boys19.32% and 36.4 (ml/kg/min) respectively. Results also revealed that there was a negative significant correlation between fat percent and aerobic fitness of boys (r = -0.81), and girls (r = -0.77) respectively. CONCLUSIONS: To conclude, this study signifies that fat percentage augmentation leads to a decrease in aerobic fitness of children. Thus, fat percentage can be associated with different chronic diseases such as cardiovascular ones. PMID- 26157559 TI - Short-term Effects of a Physical Activity Intervention on Obesity and Aerobic Fitness of Adolescent Girls. AB - BACKGROUND: In the past two decades, physical activity has decreased during both childhood and adolescence, and particularly adolescence. It seems that schools are attractive settings in which to implement interventions designed in order to promote physical activity in children; but in Iranian students, few studies have evaluated the effects of such interventions on overweight and obese children. The aim of this study was to evaluate the effects of a short-term school-based physical activity on obesity and aerobic fitness in 12-14 years aged girls. METHODS: This is a study with single group pretest and posttest design, in which 129 middle school girls in city of Isfahan were assessed based on preventive plan of inactivity in children at the Provincial Health Office. Variables, including weight, height, body mass index (BMI), waist-hip ratio (WHR), body fat percentage and aerobic power of subjects were measured using valid tests. RESULTS: This study showed that subjects' body fat percentage changed about 3.6% (37.74% pretest vs. 36.39% posttest), VO2 max changed 7.43% (29.72 pretest vs. 31.93 posttest), WHR changed 1.12% (0.89 pretest vs. 0.88 posttest), whereas BMI was changed 1.65% (27.80 pretest vs. 27.34 posttest). Findings also revealed that there were significant differences between fat percent, (P = 0.001) and VO2 max (P = 0.001) of subjects, but there was no difference between BMI of them in pre- and post-tests (P = 0.361). CONCLUSIONS: These results suggest that even a short term exercise intervention may lead to positive changes in body fat percentage, WHR and aerobic fitness of overweight children. Therefore, school-based physical activity interventions can be an effective preventive strategy to control obesity and overweight in students. PMID- 26157560 TI - Short-term Effects of a Physical Activity Intervention on Obesity and Cardiovascular Fitness of 12-14-year-old Boy Students. AB - BACKGROUND: Some local governments have implemented strategies to increase physical activity as a way to control obesity in children, but in Iranian students few studies have evaluated the effects of such interventions on overweight and obese children. The aim of this study was to evaluate the effects of a short-term school-based physical activity on obesity and cardiovascular fitness in 12-14-year-old boy students. METHODS: This study showed an intervention effect on some health-related fitness factors in students. A number of 127 boy students aged 12-14 years, in the city of Isfahan, based on preventive plan of inactivity in children at the provincial Health office selected randomly as subjects. Measurement variables include; weight, height, body mass index (BMI), waist-hip ratio (WHR), body-fat percent and aerobic power of subjects measured by valid tests. RESULTS: This study revealed that body-fat percentage of this students changed near to 17.84% (42.25% pretest vs. 34.71% posttest), WHR 0.44%, (0.915 pretest vs. 0.911 posttest), VO2 max changed 8.54% (27.84 pretest vs. 30.22 posttest) whereas BMI was changed 2.61% (26.81 pretest vs. 26.03 posttest). Results also revealed that there were significant differences between fat percent, (P = 0.001) and VO2 max (P = 0.001), but there was no difference between BMI of subjects in pre and posttests (P = 0.452). CONCLUSIONS: Findings of this study signify that an implementation of short-term intervention components in the school system may have a beneficial effect on body-fat percentage and cardiovascular fitness of overweight/obese children. PMID- 26157561 TI - Prevalence of Obesity and Overweight in 12-14-year-old Students in Isfahan-Iran. AB - BACKGROUND: Childhood obesity is a worldwide major public health problem in both developed and developing countries. The purpose of this study was to determine the prevalence of obesity and overweight in 12-14-year-old students in the city of Isfahan. METHODS: This study was conducted among 10,531 girls and 2415 boys aged 12-14 years in the city of Isfahan. Percentage of children in the corresponding body mass index (BMI) categories for overweight and obesity (specified by the Centers for Disease Control and Prevention criteria percentiles) were assessed, based on preventive plan of inactivity in children and youth of Isfahan province. RESULTS: Findings revealed that prevalence of overweight in children varied by age from 15.3% to 26.9% in boys and 12.9% to 29.9% in girls, and prevalence of obesity varied from 14.8% to 33.7% and 15% to 29.9% in boys and girls, respectively. Percentile norms for BMI of subjects were computed based on sex categories. CONCLUSIONS: To conclude, results of the study revealed that subjects have approximately the same percentage of overweight/obesity compared to other children have been studied; however, in comparison to previous studies, a higher rate was witnessed in grade 8 boy students. These situations indicate that there are needs to implement some intervention programs, as well as management policies. PMID- 26157562 TI - Knowledge and Practice of Junior and Senior High School Students Regarding Violent Behaviors in Isfahan Province. AB - BACKGROUND: Considering the importance of anger, aggression, violence and other misbehaviours in schoolchildren education, the present study was conducted to evaluate the knowledge and practice of students in Isfahan province regarding violence, in order to figure out the required interventions for violence reduction. METHODS: In a survey during 2008-2009, 5500 junior and senior high school students of Isfahan province were assessed in a multistage sampling process to determine their level of knowledge about various types of violent behaviors, causes of violence, its consequences, and preventive behaviors. Validity and reliability of the data collection tool (questionnaire) were assessed. RESULTS: The study revealed that the mean scores of violent behaviors knowledge, knowledge of violent behavior outcomes, and knowledge of violence preventive behaviors, were 6.6 +/- 2.1, 5.5 +/- 1.9, and 4.7 +/- 1.3, respectively. Sources of violent behaviors in 92% of urban students and 89% of rural students were personal reasons and family behaviors, and 85% of urban and 88% of rural students considered mass media and computer games blameworthy, and the differences were statistically significant in all cases (P < 0.0001). In terms of practice, overall, 69.7% of girls and 84.2% of boys had violent behaviors. Physical and verbal violence were 31.3% and 40.7%in girls, and 66% and 52.8% in boys, respectively (intersexes P values were P < 0.001 and P = 0.7 respectively, and intra-sex P value was P < 0.0001). CONCLUSIONS: Results showed that girls and city dwellers were more aware of recognizing violent behaviors, outcomes, and causes, compared with boys and villagers, and in terms of general practice, violence was observed among boys more than girls. Further complementary studies in this area seem required. PMID- 26157564 TI - Adolescent Perception on School Environment and Smoking Behavior: Analysis of Isfahan Tobacco use Prevention Program. AB - BACKGROUND: School provides a set of condition which is very important determinant for student smoking behavior. This study aims at exploring the association of the school environment on Iranian middle and high school students smoking. METHODS: A self-administered anonymous questionnaire was circulated among 5500 randomly selected students with 98.3% response rate. The questionnaire asked on demographic information, student smoking status, and their perception on the school environment. School environment factor was consist of teacher smoking, implementation of smoke-free policy at school, student adherence to this policy, student perception of school personnel attitude and attention on smoking and finally receiving information on smoke-related issues via teachers. Analyses were performed with SPSS software using Chi-square and multiple logistic regression. RESULTS: Boys with higher level of witness to teachers smoking had higher odds of being smoking (odds ratio [OR] =1.62, 95% confidence interval [CI] =1.17, 2.25); significant relationship was seen between boy's perception regarding school anti smoking rules and their smoking (OR = 1.40, 98% CI 1.12, 1.75); fewer concern of school personnel on student smoking behavior was correlated to boys smoking behavior (OR = 1.31, 98% CI 1.06-1.63). Among girls, only higher perceived teacher smoking (OR = 2.59, 95% CI = 1.04, 6.44) was associated with their smoking. CONCLUSIONS: Teachers have a crucial role in student smoking; therefore, they strategies must be taken to persuade the student, school staff, and students to adhere free-smoking policies in and out of school. PMID- 26157563 TI - Body Mass Index, Weight-for-age, and Stature-for-age Indices in Iranian School Children in Relation to Weight and Growth Disorders: A Population-based Survey. AB - BACKGROUND: Present study aimed to evaluate the prevalence of grades of nutritional status comprising underweight, normal weight, overweight, and obesity as well as other measurable anthropometric indicators of body mass index (BMI) in regard to gender, educational level, and living area among students settled in Isfahan province. METHODS: This cross-sectional study was conducted on a sample of 4700 individuals (2349 females and 2351 males) being from 9 to 15 years old, while they were students of either primary school or junior high school. Random cluster method was applied in both urban (84%) and rural (16%) areas of Isfahan province. BMI values were measured and then categorized using reference growth charts from the Centers for Disease Control and Prevention (CDC 2000). Weight-for age and stature-for-age indices were assessed as well in accordance with CDC growth charts. RESULTS: The overall prevalence of underweight, overweight, and obesity was 13.9, 10.4, and 5.7%, respectively. Boys and students of urban areas showed a higher tendency of obesity and overweight in comparison with girls and rural students respectively. Furthermore, rural students had poorer status in both weight-for-age and stature-for-age indices. In addition, educational level was the only statistically efficacious factor. CONCLUSIONS: This study and previous ones demonstrated that children and adolescents' nutritional status, which strongly affect general health status of individuals, should receive more exquisite attention. PMID- 26157565 TI - Development of a Questionnaire to Assess Drug Abuse among High School Students of Isfahan Province, Iran: An Action Research. AB - BACKGROUND: Considering the problem of drug abuse in Iran especially in adolescents and the youth, recent alterations in drug abuse rate and its trend, the necessity to have local information about this problem, applied research has a determining role in management of this problem and making proper decisions. Therefore, the current study was conducted to develop a questionnaire to assess the status of drug abuse among high school students of Isfahan Province, Iran. METHODS: This cross-sectional study was conducted out in 2009 in 20 cities of Isfahan Province. A researcher-made questionnaire was developed to determine knowledge, attitude, and practice of high school students regarding addictive drugs and their associated causes. This was accomplished by recruiting 7137 students who were selected by multistage random cluster sampling. RESULTS: The designed questionnaire identified the status quo of drug abuse according to age, gender, and different cities of Isfahan Province. We also accessed information about the type of abused drug, the most common causes of drug abuse for the first time, the most important causes of drug abuse, mean age of abusers and mean age at the first abuse, common time and locations of drug abuse, and the most common routes of drug abuse according to gender as well as urban and rural areas of Isfahan Province. Reliability of the questionnaire, based on the calculated Cronbach's alpha coefficient, was 77% considering a cut-off point of 0.07. CONCLUSIONS: According to the obtained results, the designed questionnaire is capable to assess the drug abuse status among high school students of Isfahan Province. Regarding the importance of teenage years in forming the future behaviors of adolescents and the opportunities provided at schools, it is prudent to pay more attention to interventions in this age group in order to increase their knowledge and correct their attitude toward illegal drugs and strengthening their confidence in this regard. These interventions can have an important role in decreasing the rate of drug abuse in this age group and consequently in the whole community. PMID- 26157566 TI - The Relationship of Parental Education with Knowledge and Practice Level of Middle School and High School Students of Isfahan Regarding Violent Behaviors. AB - BACKGROUND: It can be concluded from the existing theories that parental education status, by affecting socioeconomical status of families, can impact the incidence of violent behaviors in teenagers. Therefore, this study was conducted aiming at investigating the relationship between parental education and teenagers' knowledge of violent behaviors and their incidences. METHODS: For this cross-sectional, descriptive-correlational study, a sample of 5500 teenager students from Isfahan province were selected by random cluster sampling and responded to a 61-item questionnaire. The data collected from by questionnaire was analyzed by Spearman's statistical correlation and multiple regression methods. RESULTS: Most of the students under study (89.1%) were living in cities and the rest were rural dwellers. In terms of gender, female to male ratio was approximately equal (49.8% vs. 50.2%). The statistical results showed that there is a significant positive relationship between practice and knowledge (R = 0.092 and P = 0.00), but there is no significant relationship between parental education and practice and there is a significant relationship between parental education and knowledge (Mothers' education P = 0.00 and R = 0.121 and fathers' education P = 0.00 and R = 0.109). Moreover, there was a positive significant relationship between teenagers' knowledge of violence consequences (P = 0.005 and B = 0.048) violent behavior causes (P = 0.00 B = 0.085) and methods of preventing violent behaviors (P = 0.00 and B = 0.085) with teenagers' practice. CONCLUSIONS: Based on the results of the present study that indicates teenagers are less aware of the consequences of violent behavior compared to other subscales of knowledge, it is better that teenagers' education about the violent behaviors are more about the consequences of violent behavior rather than its definitions. Moreover, parental education is related to teenagers' knowledge of the violent behavior so it is better that in various grades more comprehensive and suitable information regarding violent behaviors be presented. PMID- 26157567 TI - The Status of School Events in Middle School Students in Isfahan Province. AB - BACKGROUND: Adolescents are being threatened by several accidents because of entering the new world of adulthood, separation from families, a greater presence in community individually, the lack of knowledge of rules and risk-taking spirit of adolescents, and events. The contribution of these damages and their related costs are higher in developing and low-income countries. The current study was conducted for proper planning focused on reducing accidents that have the highest incidence, evaluating school events, determining the place and time that most accidents happened to students and determining the body part injured. METHODS: A cross-sectional study using a multistage cluster sampling was conducted on 6933 students 11-14 years old (middle school) in 2009-2010 in Isfahan Province. The data were collected through observation and a researcher-made questionnaire and then entered into the EPi6 software, and analyzed by the SPSS 11.5 software and the statistical test of Chi-square. RESULTS: The findings showed that 49.9% of students were girls (n = 3462) and 50.1% (n = 3471) were boys, 84.5% of students (n = 5860) were living in urban areas and 15.5% of students (n = 1073) were living in rural areas. Frequency distribution of incidents was 53.9% (3739 cases) at school and 10.6% (732 cases) on the commuting route. The most injured body part was hand with 1018 cases (18.5%) and foot with 1267 cases (23.1%), and mostly they were injured in boys. CONCLUSIONS: The findings showed that a high percentage of students were injured at school, where the first step to prevent the incidence of such preventable incidents at school is to secure workshop environments and school yards. PMID- 26157568 TI - The Status of Preventive Behaviors in Traffic Accidents in Junior High School Students in Isfahan. AB - BACKGROUND: Population growth and use of the car in daily life entails new incidents and accidents everyday. Adolescents' entering the new world of adults, their insufficient knowledge of rules, and high-risk behaviors expose them to more risks. Accordingly, a study was conducted with the aim to evaluate the status of preventive behaviors in traffic accidents in boy and girl junior high school students in Isfahan regarding vehicle use. METHODS: A descriptive analytical cross-sectional study was conducted on 7000 junior high school boy and girl students from 20 towns in Isfahan Province using multi-stage cluster sampling method in 2009-2010. A researcher-made questionnaire was used as data collection tool, which evaluated students' practice and preventive behaviors with 21 questions, each examining students' practice in accidents and incidents that may occur in school and on the way to school. Data were analyzed with Epi 6 and SPSS software using t-test and Chi-square test. RESULTS: Girls comprised 49.9% of students and 50.1% were boys, 84% lived in urban areas and 15.5% in rural areas. The frequency of an accident location was school in 53.9% with 3739 cases and on the way to school in 10.6% with 732 cases. Mean practice score of preventive behaviors in traffic accidents involving cars, taxi, and school bus (72.6 +/- 17.52 girls, 72.7 +/- 18.31 boys, P = 0.88), motorbike (79.1 +/- 14.048 girls, 74.1 +/- 19.73 boys, P < 0.001), bicycle (71.4 +/- 16.56 girls, 68.5 +/- 14.69 boys, P = 0.152), bus and minibus (91.8 +/- 13.16 girls, 87 +/- 18.65 boys, P < 0.001), crossing the street (30.5 +/- 26.67 girls, 32.7 +/- 28.03 boys, P = 0.003), and skating (60.6 +/- 29.103 girls, 61.2 +/- 26.84 boys, P = 0.927). Results indicate that girls have better preventive practices than boys in use of motorbikes, buses, and minibuses. CONCLUSIONS: According to the results obtained, the majority of students walk to school and have the lowest practice score in this respect. It is recommended that as the first step, students be given necessary road traffic rules training, particularly how to cross the street. PMID- 26157569 TI - Nutritional Knowledge, Practice, and Dietary Habits among school Children and Adolescents. AB - BACKGROUND: Although nutritional status of children and adolescents is of great concern various interventions and modifications aiming at promotion of healthy eating behaviors have limited impact due to insufficient understanding of dietary habits between different age groups and genders. The aim of this study in not only evaluation of nutritional knowledge, practice, and dietary habits of primary school and junior high school students in Isfahan province, but also this research explore crucial differences regarding gender and living area of the above-mentioned population in Iran. METHODS: This cross-sectional study was conducted on 4700 primary school and junior high school pupils in Isfahan province. Data were collected through standard 24-h recall food frequency questionnaire and researcher-designed questionnaire. Independent t-test was applied for comparison of mean values of total units of consumed food materials. Qualitative variables were compared by using the Chi-square test. Data were analyzed by ACCESS 2010 and SPSS 18 software. RESULTS: Nutritional knowledge of female pupils and junior high school students was higher than their male and elementary school students respectively; still, theses superiorities did not lead to higher practice score. Bread and cereals group received daily intakes in accordance with food and drug administration (FDA) recommendations. Indeed, vegetables, milk, and dairy products, as well as meat daily intakes, were lower than the FDA recommendation, whereas fats, oils, and sugars intakes were higher. In comparison to females, male participants had significantly lower consumption of vegetables and fruits whilst they had a higher intake of carbohydrates, fats, and meats. CONCLUSIONS: Our results showed that adolescents failed to meet sufficient nutritional requirements, and they had an imbalanced diet, which was considerably low in several essential nutrients and high in some food materials. PMID- 26157570 TI - An Overview on the Comprehensive Program on Prevention and Control of High Risk Behaviors in 7-18-year-old Individuals in Isfahan, Iran. PMID- 26157571 TI - A Review Study of Substance Abuse Status in High School Students, Isfahan, Iran. AB - BACKGROUND: As the first experience of substance abuse often starts in adolescence, and studies have shown that drug use is mainly related to cigarette and alcohol consumption, an initial exploration of substance abuse prevalence, including cigarette and alcohol, seems to be the first step in preventing and controlling drug consumption. This study aimed to explore studies on drug use among high school students by investigating articles published in the past decade in Iran. METHODS: In this study, the databases inside the country were used to access articles related to substance abuse by students during 2001-2011, among which 7 articles on 14-19 years old high school students were studied. RESULTS: The seven studied articles showed that the highest drug use prevalence pertained to cigarette and hookah, followed by alcohol, opium, ecstasy, hashish and heroin. Opium and heroin use in Kerman city were, respectively, about 4 and 5 times of their use in other studied cities. CONCLUSIONS: Drug use is relatively high in the adolescent and effective group of the society, which requires particular attention and prompt and immediate intervention. PMID- 26157572 TI - Aggression and Violence among Iranian Adolescents and Youth: A 10-year Systematic Review. AB - BACKGROUND: Although the overwhelming majority of Iranian adolescents are well adjusted, a substantial group exhibits high levels of maladjustment and deficient functioning. Escalation of criminal violence among the youth population has become a major public policy issue and a serious public health problem. In reviewing a 10-year literature, this article aimed to describe and propose primary assumptions regarding the correlates of aggressive and violent behaviors in Iranian adolescents and youth. METHODS: Bibliographic databases such as PubMed and Google Scholar along with Iranian databases including PubMed, IranMedex, Magiran, Irandoc, Psychoinfo, and Emrofor Scientific Information Database, and Magiran constituted the databases which we searched for the relevant literature. Overall 98 articles met the inclusion criteria, allowing us to initiate the discussion. RESULTS: Reportedly, prevalence of violence and aggression among the Iranian adolescents and youth ranged from 30% to 65.5% while males being 21/2 times more affected than females. The role of gender, family environment, family size, socioeconomic status, and victimization in perpetuating the circumstances was apparent. CONCLUSIONS: Relatively high prevalence of violence and aggression among Iranian youth and adolescents is a warning sign and a great challenge to the social system. Reviewed studies suffer from certain methodological and conceptual limitations. Undertaking community-based studies to estimate the actual extent of the problem is warranted. PMID- 26157573 TI - The Relationships between Environmental Factors and Violent Behaviors in Adolescent Students of Isfahan, Iran. AB - BACKGROUND: Violence is a global issue that has received considerable attention during recent years. Available research has suggested various factors, mostly family and social factors, to possibly affect violence. As previous studies have not examined the relationship between these factors and violent behaviors in adolescents, this study aimed to assess the relationship between environmental factors and violence in adolescents. METHODS: This descriptive, correlational research used cluster sampling to select 5500 adolescent students from Isfahan Province (Iran). Data were collected through a 21-item researcher-made questionnaire. The questionnaire was modified according to the relevant experts' opinions and had Cronbach's alpha of 0.82. The collected data were analyzed by applying multiple regression analysis in SPSS (SPSS Inc., Chicago, IL, USA). RESULTS: Most participants (89.1%) lived in urban areas and about half (49.8%) of them were female. Linear regression test showed violent behaviors to have significant, inverse relationships with love and affection in the family (beta = 0.097; P < 0.001) and watching drama and comedy movies (beta = -0.128; P < 0.001 and beta = -0.032; P = 0.030, respectively). There were significant, direct relationships between violent behaviors in adolescents and aggressive behaviors in the family (beta =0.099; P < 0.001) and watching crime, police, and action movies (beta =0.129; P < 0.001, detective movies beta =0.043; P < 0.001, and beta =0.061; P < 0.001, respectively). However, the incidence of violent behaviors was not significantly related with the effects of peers and presence of sports facilities. CONCLUSIONS: Our findings confirmed love and affection and healthy pastime (e.g. watching comedy and drama movies) in the family to reduce violent behaviors in adolescents. In contrast, aggressive behaviors in the family, watching crime, police, and action movies were found to increase violent behaviors in adolescents. PMID- 26157575 TI - Determining the Prevalence and Seasonality of Fasciola hepatica in Pasture-based Dairy herds in Ireland using a Bulk Tank Milk ELISA. AB - BACKGROUND: Fasciola hepatica is a helminth parasite of global importance in livestock, with major economic impact. However information on F. hepatica infections in Irish pasture-based dairy herds is limited. Therefore this study was conducted in order to determine the prevalence, seasonality and management factors associated with F. hepatica. A total of 319 Irish dairy herds were selected for this study. Bulk tank milk (BTM) samples were collected from 290 dairy farms on a quarter year basis, while from a further 29 dairy farms BTM samples were collected on a monthly basis to provide a more detailed pattern of F. hepatica exposure in Irish herds. BTM samples were analysed using a commercially available F. hepatica antibody detection ELISA. Furthermore, within herd prevalence of F. hepatica was assessed in a subset of these 29 herds (n = 17); both individual serum samples and bulk tank milk samples were collected. RESULTS: A within-herd prevalence of <= 50 % was found for herds with negative bulk tank milk samples. The mean prevalence of the 290 study herds was 75.4 % (Range 52 %-75.1 %), with the highest prevalence being observed in November (75.1 %). The seasonal pattern of F. hepatica shows elevated antibodies as the grazing season progressed, reaching a peak in January. A significant association was found between F. hepatica and age at first calving. CONCLUSION: This study demonstrates that F. hepatica is present in a large proportion of Irish dairy herds and provides a basis on which control practices, particularly in adult dairy cows, can be reviewed. PMID- 26157574 TI - Wnt/beta-catenin signaling in heart regeneration. AB - The ability to repair damaged or lost tissues varies significantly among vertebrates. The regenerative ability of the heart is clinically very relevant, because adult teleost fish and amphibians can regenerate heart tissue, but we mammals cannot. Interestingly, heart regeneration is possible in neonatal mice, but this ability is lost within 7 days after birth. In zebrafish and neonatal mice, lost cardiomyocytes are regenerated via proliferation of spared, differentiated cardiomyocytes. While some cardiomyocyte turnover occurs in adult mammals, the cardiomyocyte production rate is too low in response to injury to regenerate the heart. Instead, mammalian hearts respond to injury by remodeling of spared tissue, which includes cardiomyocyte hypertrophy. Wnt/beta-catenin signaling plays important roles during vertebrate heart development, and it is re activated in response to cardiac injury. In this review, we discuss the known functions of this signaling pathway in injured hearts, its involvement in cardiac fibrosis and hypertrophy, and potential therapeutic approaches that might promote cardiac repair after injury by modifying Wnt/beta-catenin signaling. Regulation of cardiac remodeling by this signaling pathway appears to vary depending on the injury model and the exact stages that have been studied. Thus, conflicting data have been published regarding a potential role of Wnt/beta-catenin pathway in promotion of fibrosis and cardiomyocyte hypertrophy. In addition, the Wnt inhibitory secreted Frizzled-related proteins (sFrps) appear to have Wnt dependent and Wnt-independent roles in the injured heart. Thus, while the exact functions of Wnt/beta-catenin pathway activity in response to injury still need to be elucidated in the non-regenerating mammalian heart, but also in regenerating lower vertebrates, manipulation of the pathway is essential for creation of therapeutically useful cardiomyocytes from stem cells in culture. Hopefully, a detailed understanding of the in vivo role of Wnt/beta-catenin signaling in injured mammalian and non-mammalian hearts will also contribute to the success of current efforts towards developing regenerative therapies. PMID- 26157576 TI - The regulation of osteoclast differentiation by Wnt signals. AB - Wnt ligands activate beta-catenin-dependent canonical and -independent noncanonical signaling pathways. Wnt regulates many physiological events such as the development of organs and bone metabolism. In contrast, failed signaling leads to pathological conditions including cancer and osteoporosis. Analyses of loss-of-function mutations in the low-density lipoprotein receptor-related protein (Lrp) 5 gene revealed that Lrp5 acted as a co-receptor of Wnt/beta catenin signals and positively regulated bone mass in humans and mice. Many players in Wnt signals including sclerostin, an osteocyte-derived Wnt antagonist, also have since been found to influence bone mass. Bone mass is regulated by the activities of bone-forming osteoblasts, -resorbing osteoclasts and matrix embedded osteocytes. The roles of Wnt/beta-catenin signals in osteoblastogenesis and osteoclastogenesis have been established by the findings of a large number of in vitro and in vivo studies. In contrast, the roles of noncanonical Wnt signals in bone metabolism are only now being examined. In this review, we introduced and discussed recent information on the roles of Wnt signals in bone resorption. PMID- 26157577 TI - Genetic regulation of bone strength: a review of animal model studies. AB - Population- and family-based studies have established that fragility fracture risk is heritable; yet, the genome-wide association studies published to date have only accounted for a small fraction of the known variation for fracture risk of either the femur or the lumbar spine. Much work has been carried out using animal models toward finding genetic loci that are associated with bone strength. Studies using animal models overcome some of the issues associated with using patient data, but caution is needed when interpreting the results. In this review, we examine the types of tests that have been used for forward genetics mapping in animal models to identify loci and/or genes that regulate bone strength and discuss the limitations of these test methods. In addition, we present a summary of the quantitative trait loci that have been mapped for bone strength in mice, rats and chickens. The majority of these loci co-map with loci for bone size and/or geometry and thus likely dictate strength via modulating bone size. Differences in bone matrix composition have been demonstrated when comparing inbred strains of mice, and these matrix differences may be associated with differences in bone strength. However, additional work is needed to identify loci that act on bone strength at the materials level. PMID- 26157578 TI - Point mutations in an epigenetic factor lead to multiple types of bone tumors: role of H3.3 histone variant in bone development and disease. AB - Coordinated post-translational modifications (PTMs) of nucleosomal histones emerge as a key mechanism of gene regulation by defining chromatin configuration. Patterns of histone modifications vary in different cells and constitute core elements of cell-specific epigenomes. Recently, in addition to canonical histone proteins produced during the S phase of cell cycle, several non-canonical histone variants have been identified and shown to express in a DNA replication independent manner. These histone variants generate diversity in nucleosomal structures and add further complexity to mechanisms of epigenetic regulation. Cell-specific functions of histone variants remain to be determined. Several recent studies reported an association between some point mutations in the non canonical histone H3.3 and particular types of brain and bone tumors. This suggests a possibility of differential physiological effects of histone variants in different cells and tissues, including bone. In this review, we outline the roles of histone variants and their PTMs in the epigenetic regulation of chromatin structure and discuss possible mechanisms of biological effects of the non-canonical histone mutations found in bone tumors on tumorigenesis in differentiating bone stem cells. PMID- 26157580 TI - Lipid-rich diet enhances L-cell density in obese subjects and in mice through improved L-cell differentiation. AB - The enterohormone glucagon-like peptide-1 (GLP-1) is required to amplify glucose induced insulin secretion that facilitates peripheral glucose utilisation. Alteration in GLP-1 secretion during obesity has been reported but is still controversial. Due to the high adaptability of intestinal cells to environmental changes, we hypothesised that the density of GLP-1-producing cells could be modified by nutritional factors to prevent the deterioration of metabolic condition in obesity. We quantified L-cell density in jejunum samples collected during Roux-en-Y gastric bypass in forty-nine severely obese subjects analysed according to their fat consumption. In mice, we deciphered the mechanisms by which a high-fat diet (HFD) makes an impact on enteroendocrine cell density and function. L-cell density in the jejunum was higher in obese subjects consuming >30 % fat compared with low fat eaters. Mice fed a HFD for 8 weeks displayed an increase in GLP-1-positive cells in the jejunum and colon accordingly to GLP-1 secretion. The regulation by the HFD appears specific to GLP-1-producing cells, as the number of PYY (peptide YY)-positive cells remained unchanged. Moreover, genetically obese ob/ob mice did not show alteration of GLP-1-positive cell density in the jejunum or colon, suggesting that obesity per se is not sufficient to trigger the mechanism. The higher L-cell density in HFD-fed mice involved a rise in L-cell terminal differentiation as witnessed by the increased expression of transcription factors downstream of neurogenin3 (Ngn3). We suggest that the observed increase in GLP-1-positive cell density triggered by high fat consumption in humans and mice might favour insulin secretion and therefore constitute an adaptive response of the intestine to balance diet-induced insulin resistance. PMID- 26157579 TI - TGFbeta-Mediated induction of SphK1 as a potential determinant in human MDA-MB 231 breast cancer cell bone metastasis. AB - Mechanistic understanding of the preferential homing of circulating tumor cells to bone and their perturbation on bone metabolism within the tumor-bone microenvironment remains poorly understood. Alteration in both transforming growth factor beta (TGFbeta) signaling and sphingolipid metabolism results in the promotion of tumor growth and metastasis. Previous studies using MDA-MB-231 human breast cancer-derived cell lines of variable metastatic potential were queried for changes in sphingolipid metabolism genes to explore correlations between TGFbeta dependence and bone metastatic behavior. Of these genes, only sphingosine kinase-1 (SPHK1) was identified to be significantly increased following TGFbeta treatment. Induction of SPHK1 expression correlated to the degree of metastatic capacity in these MDA-MB-231-derived cell lines. We demonstrate that TGFbeta mediates the regulation of SPHK1 gene expression, protein kinase activity and is critical to MDA-MB-231 cell viability. Furthermore, a bioinformatic analysis of human breast cancer gene expression supports SPHK1 as a hallmark TGFbeta target gene that also bears the genetic fingerprint of the basal-like/triple-negative breast cancer molecular subtype. These data suggest a potential new signaling axis between TGFbeta/SphK1 that may have a role in the development, prognosis or the clinical phenotype associated with tumor-bone metastasis. PMID- 26157581 TI - Risk prediction of ICU readmission in a mixed surgical and medical population. AB - BACKGROUND: Readmission to intensive care units (ICU) is accompanied with longer ICU stay as well as higher ICU, in-hospital and 30-day mortality. Different scoring systems have been used in order to predict and reduce readmission rates. METHODS: The purpose of this study was to evaluate the Stability and Workload Index for Transfer (SWIFT) score as a predictor of readmission. Further, we wanted to study steps and measures taken at the ward prior to readmission. RESULTS: This was a retrospective study conducted at the mixed surgical and medical ICU at Linkoping University Hospital. One thousand sixty-seven patients >18 years were admitted to the ICU during 2 years and were included in the study. During the study period, 27 patients were readmitted to the ICU. Readmitted patients had a higher SWIFT score than the non-readmitted (16.1 +/- 6.8 vs. 13.0 +/- 7.5, p = 0.03) at discharge. The total ICU length of stay was longer (7.5 +/- 7.5 vs. 2.9 +/- 5.1, p = 0.004), and the 30-day mortality was higher (26 vs. 7 %, p < 0.001) for readmitted patients. Fifty-six percent of readmitted patients were assessed by the critical care outreach service (CCOS) at the ward prior to ICU readmission. A SWIFT score of 15 or more was associated with a significantly higher readmission rate (p = 0.03) as well as 30-day mortality (p < 0.001) compared to a score of <=14. CONCLUSIONS: A SWIFT score of 15 or more is associated with higher readmission rate and 30-day mortality. The SWIFT score could therefore be used for risk prediction for readmission and mortality at ICU discharge. PMID- 26157582 TI - Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study. AB - BACKGROUND: It is well known that anti-GAD (glutamic acid decarboxylase) serves as a marker for development of autoimmune diabetes in adults. On the other hand, the clinical implications of anti-GAD positivity in persistently non-diabetic (PND) adults are poorly elucidated. Our aim was to establish the frequency of anti-GAD in PNDs in an all-population-based cohort from the Nord-Trondelag health study (HUNT) and to prospectively test for associations with glucose tolerance and thyroid autoimmunity. METHODS: We formed a primary study population (4496 individuals), selected randomly from the age group 20-90 years (50% men/women), who were non-diabetic both at HUNT2 (1995-1997) and HUNT3 (2006-2008). Anti-GAD positive individuals at HUNT2, together with anti-GAD-negative individuals aged 20-29 years, were retested for anti-GAD positivity at HUNT3. A secondary study population consisted of individuals with type 2 diabetes (T2D, n=349) at HUNT3 who developed diabetes between HUNT2 and HUNT3. RESULTS: The frequency of anti GAD positivity in PND was 1.7% (n=76) at HUNT2. Positivity did not associate with gender, family history of diabetes, or glucose levels, but was associated with thyroid-associated autoimmunity (increased frequency of positivity for anti-TPO (thyroid peroxidase), p<0.002). HLA-DQA1/DQB1, a risk haplotype for autoimmunity, was also associated with anti-GAD positivity in PND. The incidence of anti-GAD positivity was low (0.4%) in the subsample of individuals who were anti-GAD negative in HUNT2. Anti-GAD positivity in PNDs was frequently evanescent, with 54% losing, usually low-grade, positivity between HUNT2 and HUNT3. An evanescent state of autoimmunity as assessed by anti-GAD positivity during "pre-diabetes" in individuals later diagnosed with T2D could, however, not be affirmed. CONCLUSIONS: Anti-GAD positivity in PND is associated with HLA risk haplotypes and thyroid autoimmunity but not with clinical parameters of diabetes. Fleeting anti-GAD positivity is common; however, results do not support the notion of a history of autoimmunity in T2D in the present cohort. PMID- 26157583 TI - An observational study of patient characteristics and mortality following hypoglycemia in the community. AB - OBJECTIVES: Characterize patients with diabetes with severe hypoglycemia requiring emergency services intervention at home and investigate 12-month mortality. RESEARCH DESIGN AND METHODS: Emergency services call-outs for hypoglycemia were recorded between 2005 and 2013 in an area covering 34 000 patients with diabetes. Patient characteristics were documented together with capillary blood glucose (CBG), glycated hemoglobin (HbA1c), and treatment for hypoglycemia; 12-month mortality and variables influencing survival were analyzed. RESULTS: In 1835 episodes among 1156 patients, 45% had type 1 diabetes (68.2% males) and 44% had type 2 diabetes (49.4% males), with a minority unclassified. CBG at presentation (mean+/-SD) was 1.76+/-0.72 mmol/L in patients with type 1 diabetes and 1.96+/-0.68 mmol/L in patients with type 2 diabetes (p<0.0001), with a higher HbA1c in the former group (8.3+/-1.52% (67.5+/-16.4 mmol/mol) and 7.8+/-1.74% (61.6+/-19.0 mmol/mol), respectively; p<0.0001). A third of patients with type 2 diabetes were not on insulin therapy and displayed lower HbA1c compared with insulin users. Glucagon was used in 37% of patients with type 1 diabetes and 28% of patients with type 2 diabetes (p<0.0001). One year mortality was 4.45% in type 1 diabetes and 22.1% in type 2 diabetes. Age and type of diabetes were predictive of mortality in multivariable analysis, whereas CBG levels/frequency of hypoglycemia had no effect. CONCLUSIONS: Severe hypoglycemia in the community is common with a male predominance in type 1 diabetes. Severe hypoglycemia in non-insulin treated patients with type 2 diabetes is associated with lower HbA1c compared with insulin users. Severe hypoglycemia appears to be associated with increased mortality at 12 months, particularly in type 2 diabetes. PMID- 26157584 TI - Lower urinary pH is useful for predicting renovascular disorder onset in patients with diabetes. AB - BACKGROUND AND OBJECTIVES: A lower urinary pH (UpH) is closely linked to diabetes. However, its relation to diabetic renovascular damage is unclear. This study aimed to identify the relationship between UpH and the exacerbation of diabetic renovascular disorders. METHODS: This is a 10-year observational study targeting 400 outpatients with diabetes who registered in 2003. We investigated the relationship between UpH in 2003 and renovascular damage from 2003 to 2013. RESULTS: A total of 350 participants were eligible for the analysis. During their 10-year outpatient treatment, a decrease was seen in glycated hemoglobin levels, blood pressure, and estimated glomerular filtration rates (eGFRs), and an increase was seen in their urinary albumin-creatinine ratios (ACRs), uric acid (UA) levels, and intima-media thickness (IMT). UpH negatively correlated with urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), body mass index, UA, and ACR, and positively correlated with eGFR. The results of a multiple regression analysis showed that the independent risk factors for UpH were 8-OHdG, UA, eGFR, and ACR. UpH also negatively correlated with the percent change in IMT (%IMT), the percent change in pulse wave velocity (%PWV), and the change in log ACR (Deltalog ACR), and positively correlated with the percent change in eGFR. A multiple regression analysis revealed that UpH was an independent risk factor for the %IMT, %PWV and Deltalog ACR. Obese patients with low UpH values frequently suffered from sleep apnea syndrome. CONCLUSIONS: These results suggest that UpH is a useful marker for predicting the onset of renovascular disorder in patients with diabetes. PMID- 26157585 TI - Artificially designed pathogens - a diagnostic option for future military deployments. AB - Diagnostic microbial isolates of bio-safety levels 3 and 4 are difficult to handle in medical field camps under military deployment settings. International transport of such isolates is challenging due to restrictions by the International Air Transport Association. An alternative option might be inactivation and sequencing of the pathogen at the deployment site with subsequent sequence-based revitalization in well-equipped laboratories in the home country for further scientific assessment. A literature review was written based on a PubMed search. First described for poliovirus in 2002, de novo synthesis of pathogens based on their sequence information has become a well established procedure in science. Successful syntheses have been demonstrated for both viruses and prokaryotes. However, the technology is not yet available for routine diagnostic purposes. Due to the potential utility of diagnostic sequencing and sequence-based de novo synthesis of pathogens, it seems worthwhile to establish the technology for diagnostic purposes over the intermediate term. This is particularly true for resource-restricted deployment settings, where safe handling of harmful pathogens cannot always be guaranteed. PMID- 26157587 TI - Spread of Efflux Pump Overexpressing-Mediated Fluoroquinolone Resistance and Multidrug Resistance in Pseudomonas aeruginosa by using an Efflux Pump Inhibitor. AB - BACKGROUND: Fluoroquinolone resistance in Pseudomonas aeruginosa may be due to efflux pump overexpression and/or target mutations. We designed this study to investigate the efflux pump mediated fluoroquinolone resistance and check the increasing effectiveness of fluoroquinolones in combination with an efflux pumps inhibitor among P. aeruginosa isolates from burn wounds infections. MATERIALS AND METHODS: A total of 154 consecutive strains of P. aeruginosa were recovered from separate patients hospitalized in a burn hospital, Tehran, Iran. The isolates first were studied by disk diffusion antibiogram for 11 antibiotics and then minimum inhibitory concentration (MIC) experiments were performed to detect synergy between ciprofloxacin and the efflux pump inhibitor, carbonyl cyanide-m chlorophenyl hydrazone (CCCP). Then to elucidate the inducing of multi drug resistance due to different efflux pumps activation in Fluoroquinolone resistant isolates, synergy experiments were also performed in random ciprofloxacin resistant isolates which have overexpressed efflux pumps phenotypically, using CCCP and selected antibiotics as markers for Beta-lactams and Aminoglycosides. The isolates were also tested by polymerase chain reaction (PCR) for the presence of the MexA, MexC and MexE, which encode the efflux pumps MexAB-OprM, MexCD-OprJ and MexEF-OprN. RESULTS: Most of the isolates were resistant to 3 or more antibiotics tested. More than half of the ciprofloxacin resistant isolates exhibited synergy between ciprofloxacin and CCCP, indicating the efflux pump activity contributed to the ciprofloxacin resistance. Also increased susceptibility of random ciprofloxacin resistant isolates of P. aeruginosa to other selected antibiotics, in presence of CCCP, implied multidrug extrusion by different active efflux pump in fluoroquinolones resistant strains. All of Ciprofloxacin resistant isolates were positive for MexA, MexC and MexE genes simultaneously. CONCLUSION: In this burn hospital, where multidrug resistant P. aeruginosa isolates were prevalent, ciprofloxacin resistance and multidrug resistance due to the overexpression of fluoroquinolones mediated efflux pumps has also now emerged. Early recognition of this resistance mechanism should allow the use of alternative antibiotics and use an efflux pumps inhibitor in combination with antibiotic therapy. PMID- 26157589 TI - Impact of an Antimicrobial Stewardship Program on Unnecessary Double Anaerobic Coverage Prescription. AB - BACKGROUND: Co-administration of two or more antimicrobials with anti-anaerobic activity is not recommended except in certain circumstances. We therefore conducted an intervention to reduce unnecessary double anaerobic coverage (DAC) prescription. MATERIALS AND METHODS: The intervention consisted of education using an institutional intranet and prospective audits and feedback provided through collaboration between a pharmacist and an infectious diseases physician in Seoul National University Bundang Hospital, a tertiary hospital in Seongnam, Republic of Korea, in 2013. The study period was 1 year which contained 6 months of pre-intervention period and 6 months of intervention period. To estimate the overall effect of the intervention, we compared the monthly number of patients receiving unnecessary DAC for more than 3 days and the proportion of patients receiving unnecessary DAC for more than 3 days among all patients receiving DAC. RESULTS: The average monthly number of patients receiving unnecessary DAC for more than 3 days after screening decreased by 73.9% in the intervention period from 26.8 to 7.0. Wilcoxon rank sum test revealed there was a significant statistical difference in the monthly number of patients receiving unnecessary DAC for more than 3 days (P = 0.005). The proportion of patients receiving unnecessary DAC for more than 3 days after screening among all patients identified as receiving necessary or unnecessary DAC also decreased by 67.8% in the intervention period from 42.3% to 13.6% (P < 0.001). CONCLUSION: The multidisciplinary antimicrobial stewardship program with combined methods reduced unnecessary DAC prescription successfully. PMID- 26157588 TI - Diagnostic Usefulness of Cytomegalovirus (CMV)-Specific T Cell Immunity in Predicting CMV Infection after Kidney Transplantation: A Pilot Proof-of-Concept Study. AB - BACKGROUND: Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Currently sero-positivity for CMV IgG before solid organ transplantation is the laboratory test of choice for stratifying the risk of CMV reactivation after solid organ transplantation. Theoretically, CMV specific cell-mediated immune responses before solid organ transplantation should further categorize patients as high or low risk of CMV development. We therefore evaluated the usefulness of the CMV-specific enzyme-linked immunospot (ELISPOT) assay in kidney transplant (KT) candidates for predicting the development of CMV infections after transplantation. MATERIALS AND METHODS: All adult CMV IgG (+) recipients admitted to the KT institute between March 2014 and June 2014 were enrolled, and CMV infections after KT were observed between March 2014 and December 2014. All patients underwent CMV pp65 and IE1-specific ELISPOT assays before transplantation. CMV infection was defined in the presence of CMV antigenemia, CMV syndrome, or tissue-invasive CMV disease. We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves. RESULTS: A total of 69 transplant recipients involving 54 (78%) living-donor KT, 9 (13%) deceased-donor KT, 3 (4%) kidney-pancreas transplants, and 3 (4%) pancreas transplants were enrolled. Of the 69 patients, 27 (39%) developed CMV infections. There was no association between the IE1-specific ELISPOT assay and CMV infection. However, only 15 (31%) of the 48 patients with positive pp65 specific ELISPOT results (>10 spots/2.0 * 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04). CONCLUSION: Negative pp65-specific ELISPOT assay results before transplantation appear to predict the subsequent development of CMV infections after transplantation in CMV IgG (+) KT recipients. Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development. PMID- 26157590 TI - Dual Time Point (18)F-FDG PET/CT Imaging Identifies Bilateral Renal Tuberculosis in an Immunocompromised Patient with an Unknown Primary Malignancy. AB - (18)F-FDG PET/CT imaging is an established imaging modality for cancer staging and response assessment. Its role in identifying infective and inflammatory pathologies from malignancy is debated. Dual time - point imaging is a refined technique used to overcome this interpretational dilemma. We present a 59 year old male with an unknown primary malignancy who was referred for a (18)F-FDG PET/CT imaging. Images revealed primary lung malignancy with co existing bilateral renal tuberculosis which otherwise would have gone amiss or would have been considered as metastases. PMID- 26157591 TI - An Unexpected Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in the Republic of Korea, 2015. AB - This report includes a summary of a current outbreak of the Middle East Respiratory Syndrome Coronavirus infection in the Republic of Korea as of June 23, 2015. Epidemiologic, clinical, and laboratory investigations of this outbreak are ongoing. PMID- 26157586 TI - Epidemiology and Characteristics of Metallo-beta-Lactamase-Producing Pseudomonas aeruginosa. AB - Metallo-beta-lactamase-producing Pseudomonas aeruginosa (MPPA) is an important nosocomial pathogen that shows resistance to all beta-lactam antibiotics except monobactams. There are various types of metallo-beta-lactamases (MBLs) in carbapenem-resistant P. aeruginosa including Imipenemase (IMP), Verona integron encoded metallo-beta-lactamase (VIM), Sao Paulo metallo-beta-lactamase (SPM), Germany imipenemase (GIM), New Delhi metallo-beta-lactamase (NDM), Florence imipenemase (FIM). Each MBL gene is located on specific genetic elements including integrons, transposons, plasmids, or on the chromosome, in which they carry genes encoding determinants of resistance to carbapenems and other antibiotics, conferring multidrug resistance to P. aeruginosa. In addition, these genetic elements are transferable to other Gram-negative species, increasing the antimicrobial resistance rate and complicating the treatment of infected patients. Therefore, it is essential to understand the epidemiology, resistance mechanism, and molecular characteristics of MPPA for infection control and prevention of a possible global health crisis. Here, we highlight the characteristics of MPPA. PMID- 26157592 TI - Fever and Prominent Arthralgia in a Traveler who Returned from Amazonia: Differentiating between Dengue Fever and Chikungunya Fever. PMID- 26157593 TI - Enterobacter cloacae Sacroiliitis with Acute Respiratory Distress Syndrome in an Adolescent. AB - Enterobacter cloacae has emerged as an important nosocomial pathogen, but is rarely a cause of sacroiliitis. Herein, we present the first reported case of Enterobacter cloacae sacroiliitis associated with sepsis and acute respiratory distress syndrome (ARDS). A previously healthy 14-year-old boy presented with low grade fever and pain in the left side of the hip that was aggravated by walking. Pelvic computed tomography (CT) showed normal findings, and the patient received supportive care for transient synovitis with no antibiotics. However, there was no clinical improvement. On the third day of hospitalization, magnetic resonance imaging of the hip revealed findings compatible with sacroiliitis, for which vancomycin and ceftriaxone were administered. The patient suddenly developed high fever with dyspnea. Chest radiography and CT findings and a PaO2/FiO2 ratio <200 mmHg were suggestive of ARDS; the patient subsequently received ventilatory support and low-dose methylprednisolone infusions. Within one week, defervescence occurred, and the patient was able to breathe on his own. Following the timely recognition of, and therapeutic challenge to, ARDS, and after 6 weeks of parenteral antimicrobial therapy, the patient was discharged in good health with no complications. PMID- 26157594 TI - Fever of Unknown Origin: An Unusual Presentation of Anti-N-Methyl-D-Aspartate Receptor Encephalitis. AB - Encephalitis associated with antibodies to the N-methyl-D-aspartate receptor (NMDAR) has variable clinical manifestations. Patients are often diagnosed with infectious processes because of prodromal symptoms and autonomic manifestations. Approximately 70% of patients have prodromal symptoms consisting of headache, fever, nausea, vomiting, and diarrhea, along with frequent autonomic manifestations, including tachycardia, and fluctuating blood pressure. A 36-year old woman presented with uncontrolled fever and skin and soft tissue infections. She had shown psychiatric symptoms and abnormal behavior, and had been diagnosed with bipolar disorder. Antibodies to NMDAR were positive in cerebrospinal fluid (CSF) and serum samples, and pelvic computed tomography detected a large ovarian teratoma. The patient improved dramatically after removal of the teratoma and administration of corticosteroid therapy. When confronted with a young woman with uncontrolled fever and acute psychiatric symptoms, physicians should suspect anti NMDAR encephalitis. PMID- 26157595 TI - Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus. AB - When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention. PMID- 26157596 TI - Toxocariasis: A Rare Cause of Multiple Cerebral Infarction. AB - Toxocariasis is a parasitic infection caused by the roundworms Toxocara canis or Toxocara cati, mostly due to accidental ingestion of embryonated eggs. Clinical manifestations vary and are classified as visceral larva migrans or ocular larva migrans according to the organs affected. Central nervous system involvement is an unusual complication. Here, we report a case of multiple cerebral infarction and concurrent multi-organ involvement due to T. canis infestation of a previous healthy 39-year-old male who was admitted for right leg weakness. After treatment with albendazole, the patient's clinical and laboratory results improved markedly. PMID- 26157597 TI - Overexpression of Efflux Pump in Multiresistant Pseudomonas aeruginosa: How You Will Discover and Treat It? PMID- 26157598 TI - Vaccination guideline for Immigrant in Korea by Korean Society of Infectious Diseases. PMID- 26157599 TI - Erratum: Revised Adult Immunization Guideline Recommended by the Korean Society of Infectious Diseases, 2014. AB - [This corrects the article on p. 68 in vol. 47, PMID: 25844267.]. PMID- 26157600 TI - Tendons, Concentric Tubes, and a Bevel Tip: Three Steerable Robots in One Transoral Lung Access System. AB - Lung cancer is the most deadly form of cancer, and survival depends on early stage diagnosis and treatment. Transoral access is preferable to traditional between-the-ribs needle insertion because it is less invasive and reduces risk of lung collapse. Yet many sites in the peripheral zones of the lung or distant from the bronchi cannot currently be accessed transorally, due to the relatively large diameter and lack of sufficient steerablity of current instrumentation. To remedy this, we propose a new robotic system that uses a tendon-actuated device (bronchoscope) as a first stage for deploying a concentric tube robot, which itself is a vehicle through which a bevel steered needle can be introduced into the soft tissue of the lung outside the bronchi. In this paper we present the various components of the system and the workflow we envision for deploying the robot to a target using image guidance. We describe initial validation experiments in which we puncture ex vivo bronchial wall tissue and also target a nodule in a phantom with an average final tip error of 0.72 mm. PMID- 26157601 TI - Niche distribution and influence of environmental parameters in marine microbial communities: a systematic review. AB - Associations between microorganisms occur extensively throughout Earth's oceans. Understanding how microbial communities are assembled and how the presence or absence of species is related to that of others are central goals of microbial ecology. Here, we investigate co-occurrence associations between marine prokaryotes by combining 180 new and publicly available metagenomic datasets from different oceans in a large-scale meta-analysis. A co-occurrence network was created by calculating correlation scores between the abundances of microorganisms in metagenomes. A total of 1,906 correlations amongst 297 organisms were detected, segregating them into 11 major groups that occupy distinct ecological niches. Additionally, by analyzing the oceanographic parameters measured for a selected number of sampling sites, we characterized the influence of environmental variables over each of these 11 groups. Clustering organisms into groups of taxa that have similar ecology, allowed the detection of several significant correlations that could not be observed for the taxa individually. PMID- 26157602 TI - Leadership and management influences the outcome of wildlife reintroduction programs: findings from the Sea Eagle Recovery Project. AB - Wildlife reintroductions and translocations are statistically unlikely to succeed. Nevertheless, they remain a critical part of conservation because they are the only way to actively restore a species into a habitat from which it has been extirpated. Past efforts to improve these practices have attributed the low success rate to failures in the biological knowledge (e.g., ignorance of social behavior, poor release site selection), or to the inherent challenges of reinstating a species into an area where threats have already driven it to local extinction. Such research presumes that the only way to improve reintroduction outcomes is through improved biological knowledge. This emphasis on biological solutions may have caused researchers to overlook the potential influence of other factors on reintroduction outcomes. I employed a grounded theory approach to study the leadership and management of a successful reintroduction program (the Sea Eagle Recovery Project in Scotland, UK) and identify four critical managerial elements that I theorize may have contributed to the successful outcome of this 50-year reintroduction. These elements are: 1. Leadership & Management: Small, dedicated team of accessible experts who provide strong political and scientific advocacy ("champions") for the project. 2. Hierarchy & Autonomy: Hierarchical management structure that nevertheless permits high individual autonomy. 3. Goals & Evaluation: Formalized goal-setting and regular, critical evaluation of the project's progress toward those goals. 4. Adaptive Public Relations: Adaptive outreach campaigns that are open, transparent, inclusive (esp. linguistically), and culturally relevant. PMID- 26157603 TI - Influence of sediment characteristics on the composition of soft-sediment intertidal communities in the northern Gulf of Mexico. AB - Benthic infaunal communities are important components of coastal ecosystems. Understanding the relationships between the structure of these communities and characteristics of the habitat in which they live is becoming progressively more important as coastal systems face increasing stress from anthropogenic impacts and changes in climate. To examine how sediment characteristics and infaunal community composition were related along the northern Gulf of Mexico coast, we sampled intertidal infaunal communities at seven sites covering common habitat types at a regional scale. Across 69 samples, the communities clustered into four distinct groups on the basis of faunal composition. Nearly 70% of the variation in the composition of the communities was explained by salinity, median grain size, and total organic content. Our results suggest that at a regional level coarse habitat characteristics are able to explain a large amount of the variation among sites in infaunal community structure. By examining the relationships between infaunal communities and their sedimentary habitats, we take a necessary first step that will allow the exploration of how changes in habitat and community composition influence higher trophic levels and ecosystem scale processes. PMID- 26157604 TI - Recent mobility of plastid encoded group II introns and twintrons in five strains of the unicellular red alga Porphyridium. AB - Group II introns are closely linked to eukaryote evolution because nuclear spliceosomal introns and the small RNAs associated with the spliceosome are thought to trace their ancient origins to these mobile elements. Therefore, elucidating how group II introns move, and how they lose mobility can potentially shed light on fundamental aspects of eukaryote biology. To this end, we studied five strains of the unicellular red alga Porphyridium purpureum that surprisingly contain 42 group II introns in their plastid genomes. We focused on a subset of these introns that encode mobility-conferring intron-encoded proteins (IEPs) and found them to be distributed among the strains in a lineage-specific manner. The reverse transcriptase and maturase domains were present in all lineages but the DNA endonuclease domain was deleted in vertically inherited introns, demonstrating a key step in the loss of mobility. P. purpureum plastid intron RNAs had a classic group IIB secondary structure despite variability in the DIII and DVI domains. We report for the first time the presence of twintrons (introns within-introns, derived from the same mobile element) in Rhodophyta. The P. purpureum IEPs and their mobile introns provide a valuable model for the study of mobile retroelements in eukaryotes and offer promise for biotechnological applications. PMID- 26157605 TI - Were early pterosaurs inept terrestrial locomotors? AB - Pterodactyloid pterosaurs are widely interpreted as terrestrially competent, erect-limbed quadrupeds, but the terrestrial capabilities of non-pterodactyloids are largely thought to have been poor. This is commonly justified by the absence of a non-pterodactyloid footprint record, suggestions that the expansive uropatagia common to early pterosaurs would restrict hindlimb motion in walking or running, and the presence of sprawling forelimbs in some species. Here, these arguments are re-visited and mostly found problematic. Restriction of limb mobility is not a problem faced by extant animals with extensive fight membranes, including species which routinely utilise terrestrial locomotion. The absence of non-pterodactyloid footprints is not necessarily tied to functional or biomechanical constraints. As with other fully terrestrial clades with poor ichnological records, biases in behaviour, preservation, sampling and interpretation likely contribute to the deficit of early pterosaur ichnites. Suggestions that non-pterodactyloids have slender, mechanically weak limbs are demonstrably countered by the proportionally long and robust limbs of many Triassic and Jurassic species. Novel assessments of pterosaur forelimb anatomies conflict with notions that all non-pterodactyloids were obligated to sprawling forelimb postures. Sprawling forelimbs seem appropriate for species with ventrally-restricted glenoid articulations (seemingly occurring in rhamphorhynchines and campylognathoidids). However, some early pterosaurs, such as Dimorphodon macronyx and wukongopterids, have glenoid arthrologies which are not ventrally restricted, and their distal humeri resemble those of pterodactyloids. It seems fully erect forelimb stances were possible in these pterosaurs, and may be probable given proposed correlation between pterodactyloid like distal humeral morphology and forces incurred through erect forelimb postures. Further indications of terrestrial habits include antungual sesamoids, which occur in the manus and pes anatomy of many early pterosaur species, and only occur elsewhere in terrestrial reptiles, possibly developing through frequent interactions of large claws with firm substrates. It is argued that characteristics possibly associated with terrestriality are deeply nested within Pterosauria and not restricted to Pterodactyloidea as previously thought, and that pterodactyloid-like levels of terrestrial competency may have been possible in at least some early pterosaurs. PMID- 26157607 TI - Is grazing exclusion effective in restoring vegetation in degraded alpine grasslands in Tibet, China? AB - Overgrazing is considered one of the key disturbance factors that results in alpine grassland degradation in Tibet. Grazing exclusion by fencing has been widely used as an approach to restore degraded grasslands in Tibet since 2004. Is the grazing exclusion management strategy effective for the vegetation restoration of degraded alpine grasslands? Three alpine grassland types were selected in Tibet to investigate the effect of grazing exclusion on plant community structure and biomass. Our results showed that species biodiversity indicators, including the Pielou evenness index, the Shannon-Wiener diversity index, and the Simpson dominance index, did not significantly change under grazing exclusion conditions. In contrast, the total vegetation cover, the mean vegetation height of the community, and the aboveground biomass were significantly higher in the grazing exclusion grasslands than in the free grazed grasslands. These results indicated that grazing exclusion is an effective measure for maintaining community stability and improving aboveground vegetation growth in alpine grasslands. However, the statistical analysis showed that the growing season precipitation (GSP) plays a more important role than grazing exclusion in which influence on vegetation in alpine grasslands. In addition, because the results of the present study come from short term (6-8 years) grazing exclusion, it is still uncertain whether these improvements will be continuable if grazing exclusion is continuously implemented. Therefore, the assessments of the ecological effects of the grazing exclusion management strategy on degraded alpine grasslands in Tibet still need long term continued research. PMID- 26157606 TI - Population structure among octocoral adults and recruits identifies scale dependent patterns of population isolation in The Bahamas. AB - Patterns of dispersal and connectivity of the Caribbean gorgonian Antillogorgia elisabethae in The Bahamas were assessed in both adults and recently settled recruits from 13 sites using microsatellite loci. Adult populations along the Little Bahama Bank (LBB) exhibited a clear pattern of isolation by distance (IBD) which described 86% of the variance in pairwise genetic distances. Estimates of dispersal based on the IBD model suggested dispersal distances along the LBB on the order of 100 m. Increasing the spatial scale to include sites separated by open ocean generated an apparent IBD signal but the relationship had a greater slope and explained less of the variance. This relationship with distance reflected both stepping stone based IBD and regional differentiation probably created by ocean currents and barriers to dispersal that are correlated with geographic distance. Analysis of recruits from 4 sites on the LBB from up to 6 years did not detect differences between years nor differences with adult populations. The result suggests that neither selection on recruits nor inter annual variation in dispersal affected adult population structure. Assignment tests of recruits indicated the most likely sources of the recruits were the local or adjacent populations. Most of the patterning in population structure in the northern Bahamas can be explained by geographic distance and oceanographic connectivity. Recognition of these complex patterns is important in developing management plans for A. elisabethae and in understanding the effects of disturbance to adult populations of A. elisabethae and similar species with limited dispersal. PMID- 26157608 TI - Global sensitivity analysis of a dynamic model for gene expression in Drosophila embryos. AB - It is well known that gene regulation is a tightly controlled process in early organismal development. However, the roles of key processes involved in this regulation, such as transcription and translation, are less well understood, and mathematical modeling approaches in this field are still in their infancy. In recent studies, biologists have taken precise measurements of protein and mRNA abundance to determine the relative contributions of key factors involved in regulating protein levels in mammalian cells. We now approach this question from a mathematical modeling perspective. In this study, we use a simple dynamic mathematical model that incorporates terms representing transcription, translation, mRNA and protein decay, and diffusion in an early Drosophila embryo. We perform global sensitivity analyses on this model using various different initial conditions and spatial and temporal outputs. Our results indicate that transcription and translation are often the key parameters to determine protein abundance. This observation is in close agreement with the experimental results from mammalian cells for various initial conditions at particular time points, suggesting that a simple dynamic model can capture the qualitative behavior of a gene. Additionally, we find that parameter sensitivites are temporally dynamic, illustrating the importance of conducting a thorough global sensitivity analysis across multiple time points when analyzing mathematical models of gene regulation. PMID- 26157609 TI - Divergent thermal specialisation of two South African entomopathogenic nematodes. AB - Thermal physiology of entomopathogenic nematodes (EPN) is a critical aspect of field performance and fitness. Thermal limits for survival and activity, and the ability of these limits to adjust (i.e., show phenotypic flexibility) depending on recent thermal history, are generally poorly established, especially for non model nematode species. Here we report the acute thermal limits for survival, and the thermal acclimation-related plasticity thereof for two key endemic South African EPN species, Steinernema yirgalemense and Heterorhabditis zealandica. Results including LT50 indicate S. yirgalemense (LT50 = 40.8 +/- 0.3 degrees C) has greater high temperature tolerance than H. zealandica (LT50 = 36.7 +/- 0.2 degrees C), but S. yirgalemense (LT50 = -2.4 +/- 0 degrees C) has poorer low temperature tolerance in comparison to H. zealandica (LT50 = -9.7 +/- 0.3 degrees C), suggesting these two EPN species occupy divergent thermal niches to one another. Acclimation had both negative and positive effects on temperature stress survival of both species, although the overall variation meant that many of these effects were non-significant. There was no indication of a consistent loss of plasticity with improved basal thermal tolerance for either species at upper lethal temperatures. At lower temperatures measured for H. zealandica, the 5 degrees C acclimation lowered survival until below -12.5 degrees C, where after it increased survival. Such results indicate that the thermal niche breadth of EPN species can differ significantly depending on recent thermal conditions, and should be characterized across a broad range of species to understand the evolution of thermal limits to performance and survival in this group. PMID- 26157610 TI - GenomePeek-an online tool for prokaryotic genome and metagenome analysis. AB - As more and more prokaryotic sequencing takes place, a method to quickly and accurately analyze this data is needed. Previous tools are mainly designed for metagenomic analysis and have limitations; such as long runtimes and significant false positive error rates. The online tool GenomePeek (edwards.sdsu.edu/GenomePeek) was developed to analyze both single genome and metagenome sequencing files, quickly and with low error rates. GenomePeek uses a sequence assembly approach where reads to a set of conserved genes are extracted, assembled and then aligned against the highly specific reference database. GenomePeek was found to be faster than traditional approaches while still keeping error rates low, as well as offering unique data visualization options. PMID- 26157612 TI - How reproducible are the measurements of leaf fluctuating asymmetry? AB - Fluctuating asymmetry (FA) represents small, non-directional deviations from perfect symmetry in morphological characters. FA is generally assumed to increase in response to stress; therefore, FA is frequently used in ecological studies as an index of environmental or genetic stress experienced by an organism. The values of FA are usually small, and therefore the reliable detection of FA requires precise measurements. The reproducibility of fluctuating asymmetry (FA) was explored by comparing the results of measurements of scanned images of 100 leaves of downy birch (Betula pubescens) conducted by 31 volunteer scientists experienced in studying plant FA. The median values of FA varied significantly among the participants, from 0.000 to 0.074, and the coefficients of variation in FA for individual leaves ranged from 25% to 179%. The overall reproducibility of the results among the participants was rather low (0.074). Variation in instruments and methods used by the participants had little effect on the reported FA values, but the reproducibility of the measurements increased by 30% following exclusion of data provided by seven participants who had modified the suggested protocol for leaf measurements. The scientists working with plant FA are advised to pay utmost attention to adequate and detailed description of their data acquisition protocols in their forthcoming publications, because all characteristics of instruments and methods need to be controlled to increase the quality and reproducibility of the data. Whenever possible, the images of all measured objects and the results of primary measurements should be published as electronic appendices to scientific papers. PMID- 26157611 TI - Bayesian phylogeny analysis of vertebrate serpins illustrates evolutionary conservation of the intron and indels based six groups classification system from lampreys for ~500 MY. AB - The serpin superfamily is characterized by proteins that fold into a conserved tertiary structure and exploits a sophisticated and irreversible suicide mechanism of inhibition. Vertebrate serpins are classified into six groups (V1 V6), based on three independent biological features-genomic organization, diagnostic amino acid sites and rare indels. However, this classification system was based on the limited number of mammalian genomes available. In this study, several non-mammalian genomes are used to validate this classification system using the powerful Bayesian phylogenetic method. This method supports the intron and indel based vertebrate classification and proves that serpins have been maintained from lampreys to humans for about 500 MY. Lampreys have fewer than 10 serpins, which expand into 36 serpins in humans. The two expanding groups V1 and V2 have SERPINB1/SERPINB6 and SERPINA8/SERPIND1 as the ancestral serpins, respectively. Large clusters of serpins are formed by local duplications of these serpins in tetrapod genomes. Interestingly, the ancestral HCII/SERPIND1 locus (nested within PIK4CA) possesses group V4 serpin (A2APL1, homolog of alpha 2 AP/SERPINF2) of lampreys; hence, pointing to the fact that group V4 might have originated from group V2. Additionally in this study, details of the phylogenetic history and genomic characteristics of vertebrate serpins are revisited. PMID- 26157613 TI - Genetic architecture of pollination syndrome transition between hummingbird specialist and generalist species in the genus Rhytidophyllum (Gesneriaceae). AB - Adaptation to pollinators is a key factor of diversification in angiosperms. The Caribbean sister genera Rhytidophyllum and Gesneria present an important diversification of floral characters. Most of their species can be divided in two major pollination syndromes. Large-open flowers with pale colours and great amount of nectar represent the generalist syndrome, while the hummingbird specialist syndrome corresponds to red tubular flowers with a less important nectar volume. Repeated convergent evolution toward the generalist syndrome in this group suggests that such transitions rely on few genes of moderate to large effect. To test this hypothesis, we built a linkage map and performed a QTL detection for divergent pollination syndrome traits by crossing one specimen of the generalist species Rhytidophyllum auriculatum with one specimen of the hummingbird pollinated R. rupincola. Using geometric morphometrics and univariate traits measurements, we found that floral shape among the second-generation hybrids is correlated with morphological variation observed between generalist and hummingbird-specialist species at the genus level. The QTL analysis showed that colour and nectar volume variation between syndromes involve each one major QTL while floral shape has a more complex genetic basis and rely on few genes of moderate effect. Finally, we did not detect any genetic linkage between the QTLs underlying those traits. This genetic independence of traits could have facilitated evolution toward optimal syndromes. PMID- 26157614 TI - Compact graphical representation of phylogenetic data and metadata with GraPhlAn. AB - The increased availability of genomic and metagenomic data poses challenges at multiple analysis levels, including visualization of very large-scale microbial and microbial community data paired with rich metadata. We developed GraPhlAn (Graphical Phylogenetic Analysis), a computational tool that produces high quality, compact visualizations of microbial genomes and metagenomes. This includes phylogenies spanning up to thousands of taxa, annotated with metadata ranging from microbial community abundances to microbial physiology or host and environmental phenotypes. GraPhlAn has been developed as an open-source command driven tool in order to be easily integrated into complex, publication-quality bioinformatics pipelines. It can be executed either locally or through an online Galaxy web application. We present several examples including taxonomic and phylogenetic visualization of microbial communities, metabolic functions, and biomarker discovery that illustrate GraPhlAn's potential for modern microbial and community genomics. PMID- 26157615 TI - Exploring the attitudes of medical faculty members and students in Pakistan towards plagiarism: a cross sectional survey. AB - Objective. The objective of this survey was to explore the attitudes towards plagiarism of faculty members and medical students in Pakistan. Methods. The Attitudes Toward Plagiarism questionnaire (ATP) was modified and distributed among 550 medical students and 130 faculty members in 7 medical colleges of Lahore and Rawalpindi. Data was entered in the SPSS v.20 and descriptive statistics were analyzed. The questionnaire was validated by principal axis factoring analysis. Results. Response rate was 93% and 73%, respectively. Principal axis factoring analysis confirmed one factor structure of ATP in the present sample. It had an acceptable Cronbach's alpha value of 0.73. There were 421 medical students (218 (52%) female, 46% 3rd year MBBS students, mean age of 20.93 +/- 1.4 years) and 95 faculty members (54.7% female, mean age 34.5 +/- 8.9 years). One fifth of the students (19.7%) trained in medical writing (19.7%), research ethics (25.2%) or were currently involved in medical writing (17.6%). Most of the faculty members were demonstrators (66) or assistant professors (20) with work experience between 1 and 10 years. Most of them had trained in medical writing (68), research ethics (64) and were currently involved in medical writing (64). Medical students and faculty members had a mean score of 43.21 (7.1) and 48.4 (5.9) respectively on ATP. Most of the respondents did not consider that they worked in a plagiarism free environment and reported that self-plagiarism should not be punishable in the same way as plagiarism. Opinion regarding leniency in punishment of younger researchers who were just learning medical writing was divided. Conclusions. The general attitudes of Pakistani medical faculty members and medical students as assessed by ATP were positive. We propose training in medical writing and research ethics as part of the under and post graduate medical curriculum. PMID- 26157616 TI - The phylogenetic affinities of the bizarre Late Cretaceous Romanian theropod Balaur bondoc (Dinosauria, Maniraptora): dromaeosaurid or flightless bird? AB - The exceptionally well-preserved Romanian dinosaur Balaur bondoc is the most complete theropod known to date from the Upper Cretaceous of Europe. Previous studies of this remarkable taxon have included its phylogenetic interpretation as an aberrant dromaeosaurid with velociraptorine affinities. However, Balaur displays a combination of both apparently plesiomorphic and derived bird-like characters. Here, we analyse those features in a phylogenetic revision and show how they challenge its referral to Dromaeosauridae. Our reanalysis of two distinct phylogenetic datasets focusing on basal paravian taxa supports the reinterpretation of Balaur as an avialan more crownward than Archaeopteryx but outside of Pygostylia, and as a flightless taxon within a paraphyletic assemblage of long-tailed birds. Our placement of Balaur within Avialae is not biased by character weighting. The placement among dromaeosaurids resulted in a suboptimal alternative that cannot be rejected based on the data to hand. Interpreted as a dromaeosaurid, Balaur has been assumed to be hypercarnivorous and predatory, exhibiting a peculiar morphology influenced by island endemism. However, a dromaeosaurid-like ecology is contradicted by several details of Balaur's morphology, including the loss of a third functional manual digit, the non ginglymoid distal end of metatarsal II, and a non-falciform ungual on the second pedal digit that lacks a prominent flexor tubercle. Conversely, an omnivorous ecology is better supported by Balaur's morphology and is consistent with its phylogenetic placement within Avialae. Our reinterpretation of Balaur implies that a superficially dromaeosaurid-like taxon represents the enlarged, terrestrialised descendant of smaller and probably volant ancestors. PMID- 26157617 TI - Histopathology of crustose coralline algae affected by white band and white patch diseases. AB - Crustose coralline algae (CCA) are major benthic calcifiers that play crucial roles in marine ecosystems, particularly coral reefs. Over the past two decades, epizootics have been reported for several CCA species on coral reefs worldwide. However, their causes remain often unknown in part because few studies have investigated CCA pathologies at a microscopic scale. We studied the cellular changes associated with two syndromes: Coralline White Band Syndrome (CWBS) and Coralline White Patch Disease (CWPD) from samples collected in Curacao, southern Caribbean. Healthy-looking tissue of diseased CCA did not differ from healthy tissue of healthy CCA. In diseased tissues of both pathologies, the three characteristic cell layers of CCA revealed cells completely depleted of protoplasmic content, but presenting an intact cell wall. In addition, CWBS showed a transition area between healthy and diseased tissues consisting of cells partially deprived of protoplasmic material, most likely corresponding to the white band characterizing the disease at the macroscopic level. This transition area was absent in CWPD. Regrowth at the lesion boundary were sometimes observed in both syndromes. Tissues of both healthy and diseased CCA were colonised by diverse boring organisms. Fungal infections associated with the diseased cells were not seen. However, other bioeroders were more abundant in diseased vs healthy CCA and in diseased vs healthy-looking tissues of diseased CCA. Although their role in the pathogenesis is unclear, this suggests that disease increases CCA susceptibility to bioerosion. Further investigations using an integrated approach are needed to carry out the complete diagnosis of these diseases. PMID- 26157618 TI - Once bitten, twice shy: experienced regret and non-adaptive choice switching. AB - When a good decision leads to a bad outcome, the experience of regret can bias subsequent choices: people are less likely to select the regret-producing alternative a second time, even when it is still objectively the best alternative (non-adaptive choice switching). The first study presented herein showed that nearly half of participants experiencing regret rejected a previous alternative they had recognized as the best one, and chose a non-optimal alternative instead. The second study investigated the mechanism underlying this bias, and results supported the hypothesis that this non-adaptive choice switching is caused by inhibition of the previous decision (direct effect of experienced regret), rather than by increased sensitivity to anticipated regret in subsequent choices (indirect effect of experienced regret mediated by anticipated regret). PMID- 26157619 TI - Enhancement of E. coli acyl-CoA synthetase FadD activity on medium chain fatty acids. AB - FadD catalyses the first step in E. coli beta-oxidation, the activation of free fatty acids into acyl-CoA thioesters. This activation makes fatty acids competent for catabolism and reduction into derivatives like alcohols and alkanes. Alcohols and alkanes derived from medium chain fatty acids (MCFAs, 6-12 carbons) are potential biofuels; however, FadD has low activity on MCFAs. Herein, we generate mutations in fadD that enhance its acyl-CoA synthetase activity on MCFAs. Homology modeling reveals that these mutations cluster on a face of FadD from which the co-product, AMP, is expected to exit. Using FadD homology models, we design additional FadD mutations that enhance E. coli growth rate on octanoate and provide evidence for a model wherein FadD activity on octanoate can be enhanced by aiding product exit. These studies provide FadD mutants useful for producing MCFA derivatives and a rationale to alter the substrate specificity of adenylating enzymes. PMID- 26157620 TI - Multi-level machine learning prediction of protein-protein interactions in Saccharomyces cerevisiae. AB - Accurate identification of protein-protein interactions (PPI) is the key step in understanding proteins' biological functions, which are typically context dependent. Many existing PPI predictors rely on aggregated features from protein sequences, however only a few methods exploit local information about specific residue contacts. In this work we present a two-stage machine learning approach for prediction of protein-protein interactions. We start with the carefully filtered data on protein complexes available for Saccharomyces cerevisiae in the Protein Data Bank (PDB) database. First, we build linear descriptions of interacting and non-interacting sequence segment pairs based on their inter residue distances. Secondly, we train machine learning classifiers to predict binary segment interactions for any two short sequence fragments. The final prediction of the protein-protein interaction is done using the 2D matrix representation of all-against-all possible interacting sequence segments of both analysed proteins. The level-I predictor achieves 0.88 AUC for micro-scale, i.e., residue-level prediction. The level-II predictor improves the results further by a more complex learning paradigm. We perform 30-fold macro-scale, i.e., protein level cross-validation experiment. The level-II predictor using PSIPRED-predicted secondary structure reaches 0.70 precision, 0.68 recall, and 0.70 AUC, whereas other popular methods provide results below 0.6 threshold (recall, precision, AUC). Our results demonstrate that multi-scale sequence features aggregation procedure is able to improve the machine learning results by more than 10% as compared to other sequence representations. Prepared datasets and source code for our experimental pipeline are freely available for download from: http://zubekj.github.io/mlppi/ (open source Python implementation, OS independent). PMID- 26157621 TI - Attitudes of medical students in Lahore, Pakistan towards the doctor-patient relationship. AB - Background. A good doctor-patient relationship is the centre stone of modern medicine. Patients are getting increasingly aware about exercising their autonomy and thus modern medicine cannot deliver all its advances to the patients if a good doctor-patient relationship is not established. We initiated this study with the aim to assess the leaning of medical students, who are the future physicians, towards either a doctor-centered or a patient-centered care, and to explore the effects of personal attributes on care such as gender, academic year, etc. Materials & Methods. A cross-sectional study was conducted between July and Sep 2013. CMH Lahore Medical and Dental College Ethical Review Committee approved the study questionnaire. The study population consisted of 1,181 medical students in years 1-5 from two medical colleges. The English version of Patient Practitioner Orientation Scale (PPOS) was used to assess attitudes of medical students towards doctor-patient relationship. PPOS yields a mean score range of 1-6, where 1 signifies tendency towards a doctor centered relationship and 6 signifies patient centered relationship. The relationship between PPOS scores and individual characteristics like gender, academic year etc. were examined by multiple regression. Results. A total of 783 students formed the final sample (response rate = 92%). Mean PPOS score of the entire sample was 3.40 (+/- .49 S.D.). Mean sharing sub-scale score was 3.18 (+/- 0.62 S.D. Mean caring sub-scale score was 3.63 (+/- 0.56 S.D.). Characteristics associated with most patient-centered attitudes were advanced academic year, having a clinical rotation, foreign background and studying in a private college. Gender, having doctor parents, relationship and residence status had no bearing on the attitudes (p > 0.05). Conclusion. Despite ongoing debate and the emphasis on a patient-centered curriculum, our study suggests that the current curriculum and its teachings are not producing the results they are designed to achieve. Students should be adequately exposed to the patients from the beginning of their medical education in clinical settings which are more sympathetic to a patient-centered care. PMID- 26157622 TI - US adolescents' friendship networks and health risk behaviors: a systematic review of studies using social network analysis and Add Health data. AB - Background. Documented trends in health-related risk behaviors among US adolescents have remained high over time. Studies indicate relationships among mutual friends are a major influence on adolescents' risky behaviors. Social Network Analysis (SNA) can help understand friendship ties affecting individual adolescents' engagement in these behaviors. Moreover, a systematic literature review can synthesize findings from a range of studies using SNA, as well as assess these studies' methodological quality. Review findings also can help health educators and promoters develop more effective programs. Objective. This review systematically examined studies of the influence of friendship networks on adolescents' risk behaviors, which utilized SNA and the Add Health data (a nationally representative sample). Methods. We employed the Matrix Method to synthesize and evaluate 15 published studies that met our inclusion and exclusion criteria, retrieved from the Add Health website and 3 major databases (Medline, Eric, and PsycINFO). Moreover, we assigned each study a methodological quality score (MQS). Results. In all studies, friendship networks among adolescents promoted their risky behaviors, including drinking alcohol, smoking, sexual intercourse, and marijuana use. The average MQS was 4.6, an indicator of methodological rigor (scale: 1-9). Conclusion. Better understanding of risky behaviors influenced by friends can be useful for health educators and promoters, as programs targeting friendships might be more effective. Additionally, the overall MQ of these reviewed studies was good, as average scores fell above the scale's mid-point. PMID- 26157623 TI - Comprehensive comparison of large-scale tissue expression datasets. AB - For tissues to carry out their functions, they rely on the right proteins to be present. Several high-throughput technologies have been used to map out which proteins are expressed in which tissues; however, the data have not previously been systematically compared and integrated. We present a comprehensive evaluation of tissue expression data from a variety of experimental techniques and show that these agree surprisingly well with each other and with results from literature curation and text mining. We further found that most datasets support the assumed but not demonstrated distinction between tissue-specific and ubiquitous expression. By developing comparable confidence scores for all types of evidence, we show that it is possible to improve both quality and coverage by combining the datasets. To facilitate use and visualization of our work, we have developed the TISSUES resource (http://tissues.jensenlab.org), which makes all the scored and integrated data available through a single user-friendly web interface. PMID- 26157624 TI - Influence of rimonabant treatment on peripheral blood mononuclear cells; flow cytometry analysis and gene expression profiling. AB - The cannabinoid receptor type 1 (CB1) antagonist rimonabant has been used as treatment for obesity. In addition, anti-proliferative effects on mitogen activated leukocytes have been demonstrated in vitro. We have previously shown that rimonabant (SR141716A) induces cell death in ex vivo isolated malignant lymphomas with high expression of CB1 receptors. Since CB1 targeting may be part of a future lymphoma therapy, it was of interest to investigate possible effects on peripheral blood mononuclear cells (PBMC) in patients treated with rimonabant. We therefore evaluated leukocyte subsets by 6 color flow cytometry in eight patients before and at treatment with rimonabant for 4 weeks. Whole-transcript gene expression profiling in PBMC before and at 4 weeks of rimonabant treatment was done using Affymetrix Human Gene 1.0 ST Arrays. Our data show no significant changes of monocytes, B cells, total T cells or T cell subsets in PBMC during treatment with rimonabant. There was a small but significant increase in CD3-, CD16+ and/or CD56+ cells after rimonabant therapy. Gene expression analysis detected significant changes in expression of genes associated with innate immunity, cell death and metabolism. The present study shows that normal monocytes and leukocyte subsets in blood remain rather constant during rimonabant treatment. This is in contrast to the induction of cell death previously observed in CB1 expressing lymphoma cells in response to treatment with rimonabant in vitro. These differential effects observed on normal and malignant lymphoid cells warrant investigation of CB1 targeting as a potential lymphoma treatment. PMID- 26157625 TI - HOODS: finding context-specific neighborhoods of proteins, chemicals and diseases. AB - Clustering algorithms are often used to find groups relevant in a specific context; however, they are not informed about this context. We present a simple algorithm, HOODS, which identifies context-specific neighborhoods of entities from a similarity matrix and a list of entities specifying the context. We illustrate its applicability by finding disease-specific neighborhoods of functionally associated proteins, kinase-specific neighborhoods of structurally similar inhibitors, and physiological-system-specific neighborhoods of interconnected diseases. HOODS can be used via a simple interface at http://hoods.jensenlab.org, from where the source code can also be downloaded. PMID- 26157626 TI - Factor structure of the happiness-increasing strategies scales (H-ISS): activities and coping strategies in relation to positive and negative affect. AB - Background. Previous research (Tkach & Lyubomirsky, 2006) shows that there are eight general happiness-increasing strategies: social affiliation, partying, mental control, goal pursuit, passive leisure, active leisure, religion, and direct attempts. The present study investigates the factor structure of the happiness-increasing strategies scales (H-ISS) and their relationship to positive and negative affect. Method. The present study used participants' (N = 1,050 and age mean = 34.21 sd = 12.73) responses to the H-ISS in structural equation modeling analyses. Affect was measured using the Positive Affect Negative Affect Schedule. Results. After small modifications we obtained a good model that contains the original eight factors/scales. Moreover, we found that women tend to use social affiliation, mental control, passive leisure, religion, and direct attempts more than men, while men preferred to engage in partying and clubbing more than women. The H-ISS explained significantly the variance of positive affect (R (2) = .41) and the variance of negative affect (R (2) = .27). Conclusions. Our study is an addition to previous research showing that the factor structure of the happiness-increasing strategies is valid and reliable. However, due to the model fitting issues that arise in the present study, we give some suggestions for improving the instrument. PMID- 26157627 TI - Photosynthetic response of Persian Gulf acroporid corals to summer versus winter temperature deviations. AB - With on-going climate change, coral susceptibility to thermal stress constitutes a central concern in reefconservation. In the Persian Gulf, coral reefs are confronted with a high seasonal variability in water temperature, and both hot and cold extremes have been associated with episodes of coral bleaching and mortality. Using physiological performance as a measure of coral health, we investigated the thermal susceptibility of the common acroporid, Acropora downingi, near Hengam Island where the temperature oscillates seasonally in the range 20.2-34.2 degrees C. In a series of two short-term experiments comparing coral response in summer versus winter conditions, we exposed corals during each season (1) to the corresponding seasonal average and extreme temperature levels in a static thermal environment, and (2) to a progressive temperature deviation from the annual mean toward the corresponding extreme seasonal value and beyond in a dynamic thermal environment. We monitored four indictors of coral physiological performance: net photosynthesis (Pn), dark respiration (R), autotrophic capability (Pn/R), and survival. Corals exposed to warming during summer showed a decrease in net photosynthesis and ultimately died, while corals exposed to cooling during winter were not affected in their photosynthetic performance and survival. Coral autotrophic capability Pn/R was lower at the warmer thermal level within eachseason, and during summer compared to winter. Corals exposed to the maximum temperature of summer displayed Pn/R < 1, inferring that photosynthetic performance could not support basal metabolic needs under this environment. Our results suggest that the autotrophic performance of the Persian Gulf A. downingi is sensitive to the extreme temperatures endured in summer, and therefore its populations may be impacted by future increases in water temperature. PMID- 26157628 TI - The last marine pelomedusoids (Testudines: Pleurodira): a new species of Bairdemys and the paleoecology of Stereogenyina. AB - The extinct Stereogenyina turtles form a relatively diverse Podocnemididae lineage, with twelve described and phylogenetically positioned species. They are characterized by a wide geographic and temporal range, from the Eocene of Africa to the Pleistocene of Southeast Asia, and a peculiar palate morphology, with a secondary palate that is unique among side-necked turtles. Here, we describe a new Stereogenyina species, based on an almost complete skull from the middle Miocene Capadare Formation, of Venezuela. A new phylogenetic analysis supports the assignment of the new species to the genus Bairdemys. Based on geometric morphometrics analyses, we related the development of the stereogenyin secondary palate with the acquisition of a durophagous diet. Based on a review of the sedimentary environments where their fossils are found, we also propose that stereogenyins were a marine radiation of podocnemidid turtles, as corroborated by previous studies of fossil eggs and limb morphology. These two inferences allowed us to hypothesize that stereogenyins occupied an ecological niche similar to that of the extant Carettini sea turtles, and that the rise of the latter group may be related to the Stereogenyina diversity fall in the end of the Miocene. PMID- 26157629 TI - Comparative analysis of tissue-specific transcriptomes in the funnel-web spider Macrothele calpeiana (Araneae, Hexathelidae). AB - The funnel-web spider Macrothele calpeiana is a charismatic Mygalomorph with a great interest in basic, applied and translational research. Nevertheless, current scarcity of genomic and transcriptomic data of this species clearly limits the research in this non-model organism. To overcome this limitation, we launched the first tissue-specific enriched RNA-seq analysis in this species using a subtractive hybridization approach, with two main objectives, to characterize the specific transcriptome of the putative chemosensory appendages (palps and first pair of legs), and to provide a new set of DNA markers for further phylogenetic studies. We have characterized the set of transcripts specifically expressed in putative chemosensory tissues of this species, much of them showing features shared by chemosensory system genes. Among specific candidates, we have identified some members of the iGluR and NPC2 families. Moreover, we have demonstrated the utility of these newly generated data as molecular markers by inferring the phylogenetic position M. calpeina in the phylogenetic tree of Mygalomorphs. Our results provide novel resources for researchers interested in spider molecular biology and systematics, which can help to expand our knowledge on the evolutionary processes underlying fundamental biological questions, as species invasion or biodiversity origin and maintenance. PMID- 26157630 TI - The destructive effect of botulinum neurotoxins on the SNARE protein: SNAP-25 and synaptic membrane fusion. AB - Synaptic exocytosis requires the assembly of syntaxin 1A and SNAP-25 on the plasma membrane and synaptobrevin 2 (VAMP2) on the vesicular membrane to bridge the two opposite membranes. It is believed that the three SNARE proteins assemble in steps along the dynamic assembly pathway. The C-terminus of SNAP-25 is known to be the target of botulinum neurotoxins (BoNT/A and BoNT/E) that block neurotransmitters release in vivo. In this study, we employed electron paramagnetic resonance (EPR) spectroscopy to investigate the conformation of the SNAP-25 C-terminus in binary and ternary SNARE complexes. The fluorescence lipid mixing assay shows that the C-terminal of SNAP-25 is essential for membrane fusion, and that the truncated SNAP-25 mutants cleaved by BoNT/A and BoNT/E display different inhibition effects on membrane fusion: SNAP-25E (Delta26) abolishes the fusion activity of the SNARE complex, while SNAP-25A (Delta9) loses most of its function, although it can still form a SDS-resistant SNARE complex as the wild-type SNAP-25. CW-EPR spectra validate the unstable structures of the SNARE complex formed by SNAP-25 mutants. We propose that the truncated SNAP-25 mutants will disrupt the assembly of the SNARE core complex, and then inhibit the synaptic membrane fusion accordingly. PMID- 26157631 TI - Species-level determination of closely related araucarian resins using FTIR spectroscopy and its implications for the provenance of New Zealand amber. AB - Some higher plants, both angiosperms and gymnosperms, can produce resins and some of these resins can polymerize and fossilize to form ambers. Various physical and chemical techniques have been used to identify and profile different plant resins and have then been applied to fossilized resins (ambers), to try to detect their parent plant affinities and understand the process of polymerization, with varying levels of success. Here we focus on resins produced from today's most resinous conifer family, the Araucariaceae, which are thought to be the parent plants of some of the Southern Hemisphere's fossil resin deposits. Fourier transform infrared (FTIR) spectra of the resins of closely related Araucariaceae species were examined to test whether they could be distinguished at genus and species level and whether the results could then be used to infer the parent plant of a New Zealand amber. The resin FTIR spectra are distinguishable from each other, and the three Araucaria species sampled produced similar FTIR spectra, to which Wollemia resin is most similar. Interspecific variability of the FTIR spectra is greatest in the three Agathis species tested. The New Zealand amber sample is similar in key shared features with the resin samples, but it does differ from the extant resin samples in key distinguishing features, nonetheless it is most similar to the resin of Agathis australis in this dataset. However on comparison with previously published FTIR spectra of similar aged amber and older (Eocene) resinites both found in coals from New Zealand and fresh Agathis australis resin, our amber has some features that imply a relatively immature resin, which was not expected from an amber of the Miocene age. PMID- 26157632 TI - Metabolic syndrome in hospitalized patients with chronic obstructive pulmonary disease. AB - Introduction. The metabolic syndrome (MS) affects 21-53% of patients with chronic obstructive pulmonary disease (COPD) with a higher prevalence in the early stages of COPD, with results being highly variable between studies. MS may also affect natural course of COPD-number of exacerbations, quality of life and lung function. Aim. To examine the prevalence of MS and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. Material and methods. 152 patients with COPD admitted for exacerbation were studied for presence of MS. All of them were also assessed for vitamin D status and diabetes mellitus type 2 (DM). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. Results. 25% of patients have MS. 23.1% of the male and 29.5% of the female patients have MS (p > 0.05). The prevalence of MS in this study is significantly lower when compared to a national representative study (44.6% in subjects over 45 years). 69.1% of all patients and 97.4% from MS patients have arterial hypertension. The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p = 0.002 and p = 0.001 respectively) and higher total CAT score (p = 0.017). Average BMI is 27.31. None of the patients have MS and BMI <25. There is a correlation between the presence of MS and DM (p = 0.008) and with the number of exacerbations in the last year (p = 0.015). There is no correlation between the presence of MS and the pulmonary function. Conclusion. This study among hospitalized COPD patients finds comparable but relatively low prevalence of MS (25%) compared to previously published data (21-53%) and lower prevalence compared to general population (44.6%). MS may impact quality of life and the number of exacerbations of COPD. Having in mind that MS is more common in the early stages and decreases with COPD progression, the COPD patients admitted for exacerbation may be considered as having advanced COPD. PMID- 26157633 TI - Identification of the underlying factor structure of the Derriford Appearance Scale 24. AB - Background. The Derriford Appearance Scale24 (DAS24) is a widely used measure of distress and dysfunction in relation to self-consciousness of appearance. It has been used in clinical and research settings, and translated into numerous European and Asian languages. Hitherto, no study has conducted an analysis to determine the underlying factor structure of the scale. Methods. A large (n = 1,265) sample of community and hospital patients with a visible difference were recruited face to face or by post, and completed the DAS24. Results. A two factor solution was generated. An evaluation of the congruence of the factor solutions on each of the the hospital and the community samples using Tucker's Coefficient of Congruence (rc = .979) and confirmatory factor analysis, which demonstrated a consistent factor structure. A main factor, general self consciousness (GSC), was represented by 18 items. Six items comprised a second factor, sexual and body self-consciousness (SBSC). The SBSC scale demonstrated greater sensitivity and specificity in identifying distress for sexually significant areas of the body. Discussion. The factor structure of the DAS24 facilitates a more nuanced interpretation of scores using this scale. Two conceptually and statistically coherent sub-scales were identified. The SBSC sub-scale offers a means of identifying distress and dysfunction around sexually significant areas of the body not previously possible with this scale. PMID- 26157634 TI - Depressive symptoms and other risk factors predicting suicide in middle-aged men: a prospective cohort study among Korean Vietnam War veterans. AB - Background. Few studies have prospectively examined whether depressive symptoms and other risk factors are associated with a higher risk of suicide death in individuals other than high-risk populations such as psychiatric patients and individuals with self-harm histories. The purpose of the study is to prospectively examine whether depressive symptoms assessed by the Beck Depression Inventory (BDI) are associated with greater risk of suicide death and whether depressive symptoms and other risk factors are independent predictors of suicide in general-risk populations. Another aim is to evaluate the sensitivity of the BDI for predicting suicide death. Methods. 10,238 Korean Vietnam War veterans (mean age: 56.3 years) who participated in two surveys in 2001 were followed up for suicide mortality over 7.5 years. Results. 41 men died by suicide. Severely depressed participants had a higher adjusted hazard ratio (aHR = 3.4; 95% CI [1.5 7.7]) of suicide than non-to-moderately depressed ones. Higher suicide risk was associated with more severe depressive symptoms (p for trend = 0.009). After adjustment for depressive symptoms and other factors, very poor health, low education, and past drinking were associated with higher suicide risk, while good health, body mass index, and marital status were not associated with suicide. The sensitivity at the cut-off score of 31 for detecting suicide was higher during the earlier 3.5 years of the follow-up (75%; 95% CI [50-90]) than during the latter 4 years (60%; 95% CI [41-76]). Conclusions. Depressive symptoms are a strong independent predictor and very poor health, low education, and drinking status may be independent predictors of future suicide. The BDI may have acceptable diagnostic properties as a risk assessment tool for identifying people with depression and suicidal potential among middle-aged men. PMID- 26157635 TI - Three dimensional reconstructions of Nummulites tests reveal complex chamber shapes. AB - Larger benthic foraminifera (LBF) are important and prolific carbonate producers both in modern and ancient shallow tropical seas. During the Paleogene the genus Nummulites was particularly abundant with a global distribution, leading it to be frequently used in biostratigraphy. However, their evolution is poorly understood as classification is Europe-centered and mostly based on external characters and equatorial thin sections. New occurrences from regions outside the northern Tethys which poorly fit in thus reference frame, show that a more rigid framework for the classification of Nummulites is needed. Here we apply micro computed tomographical scanning, a tool that recently has become available, to visualise 3D chamber shape of Nummulites djokdjokartae and compare these to traditional morphometrical characters. We find that despite the regular shape in equatorial and axial thin section the irregular 3D chamber shape is not predicted by these sections. We argue that 3D reconstructions of Nummulites tests will be a great aid in improving our understanding of lineages within the genus Nummulites, and to elucidate its evolutionary and biogeographical history. PMID- 26157636 TI - Comparing cestode infections and their consequences for host fitness in two sexual branchiopods: alien Artemia franciscana and native A. salina from syntopic populations. AB - The American brine shrimp Artemia franciscana is invasive in the Mediterranean region where it has displaced native species (the sexual A. salina, and the clonal A. parthenogenetica) from many salt pond complexes. Artemia populations are parasitized by numerous avian cestodes whose effects have been studied in native species. We present a study from the Ebro Delta salterns (NE Spain), in a salt pond where both A. franciscana and native A. salina populations coexist, providing a unique opportunity to compare the parasite loads of the two sexual species in syntopy. The native species had consistently higher infection parameters, largely because the dominant cestode in A. salina adults and juveniles (Flamingolepis liguloides) was much rarer in A. franciscana. The most abundant cestodes in the alien species were Eurycestus avoceti (in adults) and Flamingolepis flamingo (in juveniles). The abundance of E. avoceti and F. liguloides was higher in the A. franciscana population syntopic with A. salina than in a population sampled at the same time in another pond where the native brine shrimp was absent, possibly because the native shrimp provides a better reservoir for parasite circulation. Infection by cestodes caused red colouration in adult and juvenile A. salina, and also led to castration in a high proportion of adult females. Both these effects were significantly stronger in the native host than in A. franciscana with the same parasite loads. However, for the first time, significant castration effects (for E. avoceti and F. liguloides) and colour change (for six cestode species) were observed in infected A. franciscana. Avian cestodes are likely to help A. franciscana outcompete native species. At the same time, they are likely to reduce the production of A. franciscana cysts in areas where they are harvested commercially. PMID- 26157637 TI - Community- and population-level changes in diatom size structure in a subarctic lake over the last two centuries. AB - Climate change over the last two centuries has been associated with significant shifts in diatom community structure in lakes from the high arctic to temperate latitudes. To test the hypotheses that recent climate warming selects for species of smaller size within communities and a decrease in the average size of species within populations, we quantified the size of individual diatom valves from 10 depths in a sediment core covering the last ~200 years from a pristine subarctic lake. Over the last ~200 years, changes in the relative abundance of species of different average size and changes in the average valve size of populations of species contribute equally to the changes in community size structure, but are often opposite in sign, compensating for one another and moderating temporal changes in community size structure. In the surface sediments that correspond to the recent decades when air temperatures have warmed, the mean size of valves in the diatom community has significantly decreased due to an increase in the proportion of smaller-sized planktonic diatom species. PMID- 26157639 TI - Powerline noise elimination in biomedical signals via blind source separation and wavelet analysis. AB - The distortion of biomedical signals by powerline noise from recording biomedical devices has the potential to reduce the quality and convolute the interpretations of the data. Usually, powerline noise in biomedical recordings are extinguished via band-stop filters. However, due to the instability of biomedical signals, the distribution of signals filtered out may not be centered at 50/60 Hz. As a result, self-correction methods are needed to optimize the performance of these filters. Since powerline noise is additive in nature, it is intuitive to model powerline noise in a raw recording and subtract it from the raw data in order to obtain a relatively clean signal. This paper proposes a method that utilizes this approach by decomposing the recorded signal and extracting powerline noise via blind source separation and wavelet analysis. The performance of this algorithm was compared with that of a 4th order band-stop Butterworth filter, empirical mode decomposition, independent component analysis and, a combination of empirical mode decomposition with independent component analysis. The proposed method was able to expel sinusoidal signals within powerline noise frequency range with higher fidelity in comparison with the mentioned techniques, especially at low signal-to-noise ratio. PMID- 26157638 TI - A pilot study to investigate if New Zealand men with prostate cancer benefit from a Mediterranean-style diet. AB - Carcinoma of the prostate is the most commonly diagnosed malignancy and the third leading cause of mortality in New Zealand men, making it a significant health issue in this country. Global distribution patterns suggest that diet and lifestyle factors may be linked to the development and progression of this cancer. Twenty men with diagnosed prostate cancer adhered to a Mediterranean diet, with specific adaptations, for three months. Prostate-specific antigen, C reactive protein and DNA damage were evaluated at baseline and after three months of following the diet. Dietary data were collated from diet diaries and an adaptation of a validated Mediterranean diet questionnaire. A significant reduction in DNA damage compared to baseline was apparent, with particular benefit noted for overall adherence to the diet (p = 0.013), increased intake of folate (p = 0.023), vitamin C (p = 0.007), legumes (p = 0.004) and green tea (p = 0.002). Higher intakes of red meat and dairy products were inversely associated with DNA damage (p = 0.003 and p = 0.008 respectively). The results from this small feasibility study suggest that a high-antioxidant diet, modelled on Mediterranean traditions, may be of benefit for men with prostate cancer. Protection against DNA damage appears to be associated with the diet implemented, ostensibly due to reduction in reactive oxidant species. These findings warrant further exploration in a longer trial, with a larger cohort. PMID- 26157640 TI - Mice that gorged during dietary restriction increased foraging related behaviors and differed in their macronutrient preference when released from restriction. AB - Caloric restriction (CR) can trigger gorging behavior. We examined macronutrient choice and behavior in mice that gorged during restriction compared to restricted non-gorgers and controls. Fifty MF1 male mice were restricted to 75% of ad libitum food intake (FI), while ten controls were fed ad-lib. Body mass (BM) and FI were measured two and 24-h after food inclusion over 14-days. 'Gorging' mice were defined as those which ate over 25% of their daily FI in 2-h. The top 11 gorgers and the lowest 9 gorgers, along with 10 controls, had their behavior analysed during restriction, and were then provided with an unrestricted food choice, consisting of three diets that were high in fat, protein or carbohydrate. During restriction gorgers ate on average 51% of their daily FI in the 2-h following food introduction while the non-gorgers ate only 16%. Gorgers lost significantly more BM than non-gorgers possibly due to an increased physical activity linked to anticipation of daily food provision. Controls and non-gorgers spent most of their time sleeping. After restriction, both gorgers and non gorgers were hyperphagic until their lost weight was regained. All 3 groups favoured high fat food. Gorgers and non-gorgers had a significantly greater high carbohydrate diet intake than controls, and gorgers also had a significantly greater high protein diet intake than non-gorgers and controls. On unrestricted food, they did not continue to gorge, although they still had a significantly greater 2-h FI than the other groups. Elevated protein intake may play an important role in the recovery of the lost lean tissue of gorgers after restriction. PMID- 26157641 TI - A universal approach to determine footfall timings from kinematics of a single foot marker in hoofed animals. AB - The study of animal movement commonly requires the segmentation of continuous data streams into individual strides. The use of forceplates and foot-mounted accelerometers readily allows the detection of the foot-on and foot-off events that define a stride. However, when relying on optical methods such as motion capture, there is lack of validated robust, universally applicable stride event detection methods. To date, no method has been validated for movement on a circle, while algorithms are commonly specific to front/hind limbs or gait. In this study, we aimed to develop and validate kinematic stride segmentation methods applicable to movement on straight line and circle at walk and trot, which exclusively rely on a single, dorsal hoof marker. The advantage of such marker placement is the robustness to marker loss and occlusion. Eight horses walked and trotted on a straight line and in a circle over an array of multiple forceplates. Kinetic events were detected based on the vertical force profile and used as the reference values. Kinematic events were detected based on displacement, velocity or acceleration signals of the dorsal hoof marker depending on the algorithm using (i) defined thresholds associated with derived movement signals and (ii) specific events in the derived movement signals. Method comparison was performed by calculating limits of agreement, accuracy, between horse precision and within-horse precision based on differences between kinetic and kinematic event. In addition, we examined the effect of force thresholds ranging from 50 to 150 N on the timings of kinetic events. The two approaches resulted in very good and comparable performance: of the 3,074 processed footfall events, 95% of individual foot on and foot off events differed by no more than 26 ms from the kinetic event, with average accuracy between -11 and 10 ms and average within- and between horse precision <=8 ms. While the event-based method may be less likely to suffer from scaling effects, on soft ground the threshold based method may prove more valuable. While we found that use of velocity thresholds for foot on detection results in biased event estimates for the foot on the inside of the circle at trot, adjusting thresholds for this condition negated the effect. For the final four algorithms, we found no noteworthy bias between conditions or between front- and hind-foot timings. Different force thresholds in the range of 50 to 150 N had the greatest systematic effect on foot off estimates in the hind limbs (up to on average 16 ms per condition), being greater than the effect on foot-on estimates or foot-off estimates in the forelimbs (up to on average +/-7 ms per condition). PMID- 26157643 TI - A new perspective on how humans assess their surroundings; derivation of head orientation and its role in 'framing' the environment. AB - Understanding the way humans inform themselves about their environment is pivotal in helping explain our susceptibility to stimuli and how this modulates behaviour and movement patterns. We present a new device, the Human Interfaced Personal Observation Platform (HIPOP), which is a head-mounted (typically on a hat) unit that logs magnetometry and accelerometry data at high rates and, following appropriate calibration, can be used to determine the heading and pitch of the wearer's head. We used this device on participants visiting a botanical garden and noted that although head pitch ranged between -80 degrees and 60 degrees , 25% confidence limits were restricted to an arc of about 25 degrees with a tendency for the head to be pitched down (mean head pitch ranged between -43 degrees and 0 degrees ). Mean rates of change of head pitch varied between 0.00187 degrees /0.1 s and 0.00187 degrees /0.1 s, markedly slower than rates of change of head heading which varied between -0.3141 degrees /0.1 s and 0.01263 degrees /0.1 s although frequency distributions of both parameters showed them to be symmetrical and monomodal. Overall, there was considerable variation in both head pitch and head heading, which highlighted the role that head orientation might play in exposing people to certain features of the environment. Thus, when used in tandem with accurate position-determining systems, the HIPOP can be used to determine how the head is orientated relative to gravity and geographic North and in relation to geographic position, presenting data on how the environment is being 'framed' by people in relation to environmental content. PMID- 26157644 TI - Lack of association of vitamin D receptor BsmI gene polymorphism with bone mineral density in Spanish postmenopausal women. AB - Osteoporosis is a polygenic disorder that is determined by the effects of several genes, each with relatively modest effects on bone mass. The aim of this study was to determine whether the vitamin D receptor single nucleotide polymorphism BsmI is associated with bone mineral density (BMD) in Spanish postmenopausal women. A total of 210 unrelated healthy postmenopausal women aged 60 +/- 8 years were genotyped using TaqMan((r)) SNP Genotyping Assays. Lumbar and femoral BMD were determined by dual-energy X-ray absorptiometry (DEXA). Daily calcium and vitamin D intake were determined by a food questionnaire. No differences were found in the femoral neck, trochanter, Ward's Triangle, L2, L3, L4, L2-L4, or between the femoral neck and total hip BMD after further adjustment for potential confounding factors (P > 0.05) (age, BMI, years since menopause and daily calcium intake). The BsmI polymorphism in the VDR gene was not associated with BMD in Spanish postmenopausal women. PMID- 26157642 TI - A reproducible approach to high-throughput biological data acquisition and integration. AB - Modern biological research requires rapid, complex, and reproducible integration of multiple experimental results generated both internally and externally (e.g., from public repositories). Although large systematic meta-analyses are among the most effective approaches both for clinical biomarker discovery and for computational inference of biomolecular mechanisms, identifying, acquiring, and integrating relevant experimental results from multiple sources for a given study can be time-consuming and error-prone. To enable efficient and reproducible integration of diverse experimental results, we developed a novel approach for standardized acquisition and analysis of high-throughput and heterogeneous biological data. This allowed, first, novel biomolecular network reconstruction in human prostate cancer, which correctly recovered and extended the NFkappaB signaling pathway. Next, we investigated host-microbiome interactions. In less than an hour of analysis time, the system retrieved data and integrated six germ free murine intestinal gene expression datasets to identify the genes most influenced by the gut microbiota, which comprised a set of immune-response and carbohydrate metabolism processes. Finally, we constructed integrated functional interaction networks to compare connectivity of peptide secretion pathways in the model organisms Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa. PMID- 26157645 TI - Deep sequencing of the viral phoH gene reveals temporal variation, depth-specific composition, and persistent dominance of the same viral phoH genes in the Sargasso Sea. AB - Deep sequencing of the viral phoH gene, a host-derived auxiliary metabolic gene, was used to track viral diversity throughout the water column at the Bermuda Atlantic Time-series Study (BATS) site in the summer (September) and winter (March) of three years. Viral phoH sequences reveal differences in the viral communities throughout a depth profile and between seasons in the same year. Variation was also detected between the same seasons in subsequent years, though these differences were not as great as the summer/winter distinctions. Over 3,600 phoH operational taxonomic units (OTUs; 97% sequence identity) were identified. Despite high richness, most phoH sequences belong to a few large, common OTUs whereas the majority of the OTUs are small and rare. While many OTUs make sporadic appearances at just a few times or depths, a small number of OTUs dominate the community throughout the seasons, depths, and years. PMID- 26157647 TI - Whats new in critical illness and injury science: Predicting mortality in trauma! PMID- 26157646 TI - Microwave & Magnetic (M2) Proteomics of a Mouse Model of Mild Traumatic Brain Injury. AB - Short-term increases in oxidative stress and decreases in motor function, including debilitating effects on balance and motor control, can occur following primary mild traumatic brain injuries (mTBI). However, the long-term effects on motor unit impairment and integrity as well as the molecular mechanisms underlying secondary injuries are poorly understood. We hypothesized that changes in central nervous system-specific protein (CSP) expression might correlate to these long-term effects. To test our hypothesis, we longitudinally assessed a closed-skull mTBI mouse model, vs. sham control, at 1, 7, 30, and 120 days post injury. Motor impairment was determined by rotarod and grip strength performance measures, while motor unit integrity was determined using electromyography. Relative protein expression was determined by microwave & magnetic (M2) proteomics of ipsilateral brain tissue, as previously described. Isoprostane measurements were performed to confirm a primary oxidative stress response. Decoding the relative expression of 476 +/- 56 top-ranked proteins for each specimen revealed statistically significant changes in the expression of two well known CSPs at 1, 7 and 30 days post-injury: P < 0.001 for myelin basic protein (MBP) and P < 0.05 for myelin associated glycoprotein (MAG). This was confirmed by Western blot. Moreover, MAG, alphaII-spectrin (SPNA2) and neurofilament light (NEFL) expression at 30 days post-injury were directly related to grip strength (P < 0.05). While higher-powered studies of larger cohorts merit further investigation, this study supports the proof-of-concept that M2 proteomics is a rapid method to quantify putative protein biomarkers and therapeutic targets of mTBI and suggests the feasibility of CSP expression correlations to long-term effects on motor impairment. PMID- 26157648 TI - Predictors of 1 year mortality in adult injured patients admitted to the trauma center. AB - BACKGROUND: Traditional approach to predicting trauma-related mortality utilizes scores based on anatomical, physiological, or a combination of both types of criteria. However, several factors are reported in literature to predict mortality independent of severity scores. The objectives of the study were to identify predictors of 1 year mortality and determine their magnitude and significance of association in a resource constrained scenario. MATERIALS AND METHODS: Prospective observational study enrolled 572 patients. Information regarding factors known to affect mortality was recorded. Other factors which may be important in resource constrained settings were also included. This included referral from a peripheral hospital, number of surgeries performed on the patient, and his socioeconomic status (below poverty line (BPL) card). Patients were followed till death or upto a period of 1year. Logistic regression, actuarial survival analysis, and Cox proportionate hazard model were used to identify predictors of 1year mortality. Limited estimate of external validity of the study was obtained using bootstrapping. RESULTS: Age of patient, Injury Severity Score (ISS), abnormal activated partial thromboplastin time (APTT), Glasgow Coma Scale (GCS) score at admission, and systolic blood pressure (BP) at admission were found to significantly predict mortality on logistic regression and Cox proportionate hazard models. Abnormal respiratory rate at admission was found to significantly predict mortality in the logistic regression model, but no such association was seen in Cox proportionate hazard model. Bootstrapping of the logistic regression model and Cox proportionate hazard model provide us with a set of factors common to both the models. These were age, ISS, APTT, and GCS score at admission. CONCLUSION: Multivariate analysis (logistic and Cox proportionate hazard analysis) and subsequent bootstrapping provide us with a set of factors which may be considered as valid predictors universally. However, since bootstrapping only provides limited estimates of external validity, there is a need to test these factors against the well accepted requirements of external validity namely population, ecological, and temporal validity. PMID- 26157649 TI - Dynamic behavior of venous collapsibility and central venous pressure during standardized crystalloid bolus: A prospective, observational, pilot study. AB - INTRODUCTION: Measurement of intravascular volume status is an ongoing challenge for physicians in the surgical intensive care unit (SICU). Most surrogates for volume status, including central venous pressure (CVP) and pulmonary artery wedge pressure, require invasive lines associated with a number of potential complications. Sonographic assessment of the collapsibility of the inferior vena cava (IVC) has been described as a noninvasive method for determining volume status. The purpose of this study was to analyze the dynamic response in IVC collapsibility index (IVC-CI) to changes in CVP in SICU patients receiving fluid boluses for volume resuscitation. MATERIALS AND METHODS: A prospective pilot study was conducted on a sample of SICU patients who met clinical indications for intravenous (IV) fluid bolus and who had preexisting central venous access. Boluses were standardized to crystalloid administration of either 500 mL over 30 min or 1,000 mL over 60 min, as clinically indicated. Concurrent measurements of venous CI (VCI) and CVP were conducted right before initiation of IV bolus (i.e. time 0) and then at 30 and 60 min (as applicable) after bolus initiation. Patient demographics, ventilatory parameters, and vital sign assessments were recorded, with descriptive outcomes reported due to the limited sample size. RESULTS: Twenty patients received a total of 24 IV fluid boluses. There were five recorded 500 mL boluses given over 30 min and 19 recorded 1,000 mL boluses given over 60 min. Mean (median) CVP measured at 0, 30, and 60 minutes post-bolus were 6.04 +/- 3.32 (6.5), 9.00 +/- 3.41 (8.0), and 11.1 +/- 3.91 (12.0) mmHg, respectively. Mean (median) IVC-CI values at 0, 30, and 60 min were 44.4 +/- 25.2 (36.5), 26.5 +/- 22.8 (15.6), and 25.2 +/- 21.2 (14.8), respectively. CONCLUSIONS: Observable changes in both VCI and CVP are apparent during an infusion of a standardized fluid bolus. Dynamic changes in VCI as a measurement of responsiveness to fluid bolus are inversely related to changes seen in CVP. Moreover, an IV bolus tends to produce an early response in VCI, while the CVP response is more gradual. Given the noninvasive nature of the measurement technique, VCI shows promise as a method of dynamically measuring patient response to fluid resuscitation. Further studies with larger sample sizes are warranted. PMID- 26157650 TI - Comparative study on the prognosis of critical ill patients transferred from another island compared to those patients transferred from emergency department to intensive care unit. AB - OBJECTIVE: To compare outcomes of critically ill patients transferred from another island compared to those patients with direct admission from Emergency Department to intensive care unit (ICU). PATIENTS AND METHODS: Retrospective study of prospectively collected data during 8 years. The population studied was all critical adult patients transferred from another island to our hospital and those directly admitted from the Emergency Department. Variables were age, sex, clinical diagnosis (coronary, medical, surgical, or trauma), acute physiology and chronic health evaluation (APACHE) II score at admission, ICU days of stay, days of mechanical ventilation and ICU mortality. RESULTS: During the period of study, 3,115 patients coming from Emergency Department (Group 1) were admitted to our ICU and 138 were transferred from another island (Group 2). No significant statistically differences were found between both groups neither age, sex, APACHE II, ICU days, days of mechanical ventilation, and mortality rate (17.5% versus 20.3%, P = 0.43). The multivariate analysis showed that age, APACHE II score, ICU days of stay, type of patient, and days of mechanical ventilation were independent variables associated with mortality. CONCLUSIONS: No differences were found in the global prognosis of the admitted patients transferred from another island compared to those who were admitted directly from the Emergency Department. There is no impact on mortality in transferring a patient in our study population. PMID- 26157651 TI - Ultra fast-track extubation in heart transplant surgery patients. AB - BACKGROUND: Heart transplant surgeries using cardiopulmonary bypass (CPB) typically requires mechanical ventilation in intensive care units (ICU) in post operation period. Ultra fast-track extubation (UFE) have been described in patients undergoing various cardiac surgeries. AIM: To determine the possibility of ultra-fast-track extubation instead of late extubation in post heart transplant patients. MATERIALS AND METHODS: Patients randomly assigned into two groups; Ultra fast-track extubation (UFE) group was defined by extubation inside operating room right after surgery. Late extubation group was defined by patients who were not extubated in operating room and transferred to post operation cardiac care unit (CCU) to extubate. RESULTS: The mean cardiopulmonary bypass time was 136.8 +/- 25.7 minutes in ultra-fast extubation and 145.3 +/- 29.8 minutes in late extubation patients (P > 0.05). Mechanical ventilation duration (days) was 0 days in ultra-fast and 2.31 +/- 1.8 days in late extubation. Length of ICU stay was significantly higher in late extubation group (4.2 +/- 1.2 days) than the UFE group (1.72 +/- 1.5 days) (P = 0.02). In survival analysis there was no significant difference between ultra-fast and late extubation groups (Log-rank test, P = 0.9). CONCLUSIONS: Patients undergoing cardiac transplant could be managed with "ultra-fast-track extubation", without increased morbidity and mortality. PMID- 26157652 TI - A new approach using high volume blood patch for prevention of post-dural puncture headache following intrathecal catheter pump exchange. AB - BACKGROUND: In an observational study, complications of intrathecal catheter pumps necessitating surgical exchange were analyzed. Also the use of a high volume prophylactic epidural blood patch (EBP) during surgery for preventing post dural puncture headache (PDPH) with a follow-up for 1 year is described. MATERIALS AND METHODS: In 22 patients with refractory chronic pain of cancer/noncancer origin or severe spasticity, who were receiving intrathecal morphine including adjuvants or baclofen for symptom relief, catheter exchange with or without pump was performed. In patients with documented symptoms of PDPH following initial intrathecal catheter implantation, a prophylactic EBP with a high blood volume was used for PDPH prevention during surgery. Catheters were replaced using 40 mL EBP before entering dural space at a speed of 5mL/min into the epidural space. Patients were asked to quantify pain experience and functional ability. RESULTS: From a sample of 72 patients admitted for catheter exchange with or without pump, 22 patients (33%) (12 male, 10 female) had a history of PDPH following initial implantation. Diagnostic and therapeutic measures occurring with malfunction of intrathecal catheter pump systems were described. Twenty-one patients were successfully treated with prophylactic EBP, while one patient could not be properly evaluated because of intracranial bleeding as the underlying disease. CONCLUSIONS: A new approach using a high volume prophylactic EBP for preventing PDPH following catheter exchange is presented. The efficacy and safety of this technique for 1 year follow-up have been evaluated and was found to be safe and potentially effective. PMID- 26157653 TI - An epidemiological study of the burden of trauma in Makurdi, Nigeria. AB - BACKGROUND: Trauma leads to considerable morbidity and mortality. The aim of this study is to elucidate the pattern and characteristics of trauma at Benue State University Teaching Hospital (BSUTH), Makurdi, Nigeria. MATERIALS AND METHODS: Case records of all patients who presented to the Accident and Emergency (A and E) Department with trauma between January and December 2013 were analyzed for demographic data, types of injuries sustained, causes and circumstances of injuries, as well as outcome of treatment were extracted from the case files and entered onto a computerized questionnaire. Data were analyzed using the software Statistical Package for Social Sciences for Windows version 15.0 (SPSS Inc; Chicago, Illinois). RESULTS: A total of 250 traumatized patients were studied consisting of 203 (81.2%) males and 47 (18.8%) females with a modal age group of 21-30 years. Unintentional injuries were the most predominant form of trauma (n = 209, 83.6%) with road traffic accidents being the leading cause (n = 180, 72.0%). Open wounds (n = 95, 28.2%) were the most common form of injury sustained and the extremities (n = 148, 43.5%), the most frequently injured body region. Most patients (n = 133, 53.2%) were treated and discharged home without permanent disabilities, while death occurred in 15.2%. CONCLUSION: Trauma in Makurdi is a predominantly young adult male occurrence with road traffic accidents being the leading etiological factor. Reducing road traffic accidents will likely reduce mortality and morbidity due to trauma. PMID- 26157654 TI - Cardiac dysfunction following brain death after severe pediatric traumatic brain injury: A preliminary study of 32 children. AB - BACKGROUND: Cardiac dysfunction after brain death has been described in a variety of brain injury paradigms but is not well understood after severe pediatric traumatic brain injury (TBI). Cardiac dysfunction may have implications for organ donation in this patient population. MATERIALS AND METHODS: We conducted a retrospective cohort study of pediatric patients with severe TBI, both with and without a diagnosis of brain death, who underwent echocardiography during the first 2 weeks after TBI, between the period of 2003-2011. We examined cardiac dysfunction in patients with and without a diagnosis of brain death. RESULTS: In all, 32 (2.3%) of 1,413 severe pediatric TBI patients underwent echocardiogram evaluation. Most patients had head abbreviated injury score 5 (range 2-6) and subdural hematoma (34.4%). Ten patients with TBI had brain death compared with 22 severe TBI patients who did not have brain death. Four (40%) of 10 pediatric TBI patients with brain death had a low ejection fraction (EF) compared with 1 (4.5%) of 22 pediatric TBI patients without brain death who had low EF (OR = 14, P = 0.024). CONCLUSIONS: The incidence of cardiac dysfunction is higher among pediatric severe TBI patients with a diagnosis of brain death, as compared to patients without brain death. This finding may have implications for cardiac organ donation from this population and deserves further study. PMID- 26157655 TI - Eliciting road traffic injuries cost among Iranian drivers' public vehicles using willingness to pay method. AB - BACKGROUND AND AIM: To allocate resources at the national level and ensure the safety level of roads with the aim of economic efficiency, cost calculation can help determine the size of the problem and demonstrate the economic benefits resulting from preventing such injuries. This study was carried out to elicit the cost of traffic injuries among Iranian drivers of public vehicles. MATERIALS AND METHODS: In a cross-sectional study, 410 drivers of public vehicles were randomly selected from all the drivers in city of Tehran, Iran. The research questionnaire was prepared based on the standard for willingness to pay (WTP) method (stated preference (SP), contingent value (CV), and revealed preference (RP) model). Data were collected along with a scenario for vehicle drivers. Inclusion criteria were having at least high school education and being in the age range of 18 to 65 years old. Final analysis of willingness to pay was carried out using Weibull model. RESULTS: Mean WTP was 3,337,130 IRR among drivers of public vehicles. Statistical value of life was estimated 118,222,552,601,648 IRR, for according to 4,694 dead drivers, which was equivalent to 3,940,751,753 $ based on the dollar free market rate of 30,000 IRR (purchase power parity). Injury cost was 108,376,366,437,500 IRR, equivalent to 3,612,545,548 $. In sum, injury and death cases came to 226,606,472,346,449 IRR, equivalent to 7,553,549,078 $. Moreover in 2013, cost of traffic injuries among the drivers of public vehicles constituted 1.25% of gross national income, which was 604,300,000,000$. WTP had a significant relationship with gender, daily payment, more payment for time reduction, more pay to less traffic, and minibus drivers. CONCLUSION: Cost of traffic injuries among drivers of public vehicles included 1.25% of gross national income, which was noticeable; minibus drivers had less perception of risk reduction than others. PMID- 26157656 TI - Prior cholecystectomy predisposes to acute pancreatitis in codeine-prescribed patients. AB - In this paper, we report a case of drug-induced pancreatitis just after taking a pain pill including a low-dose combination of acetaminophen and codeine. Codeine induced pancreatitis has been rarely reported, however, well-established. The proposed mechanism for codeine-induced pancreatitis is by increasing Oddi sphincter pressure. However, the clinically important point is that the codeine induced pancreatitis is seen almost only in the cholecystectomized patients due to lacking of its reservoir capacity. Codeine is commonly used alone or in combination in pain medicine. Therefore, it is fairly important to question whether a patient underwent cholecystectomy when a physician decides to prescribe codeine-included preparations. PMID- 26157657 TI - Tracheobronchial injury due to blunt chest trauma. AB - Tracheobronchial avulsion resulting from blunt trauma is a very rare and serious condition, mostly due to high-speed traffic crashes. In this article, we briefly report the case of an 18-year-old man who was injured in a car accident and because of massive persistent air leakage (despite appropriate chest tube drainage), deemed to have a deep tracheobronchial injury. Due to a rapid drop in the patient's O2 saturation, he underwent an anterolateral thoracotomy. Endotracheal intubation was performed under direct visualization. The right mainstem bronchus was disrupted from the carina with a 1.5-cm stump remaining on the carina, and the remainder was crushed to the origin of the right superior lobe bronchus. Hence, a right superior lobectomy was performed and the postoperative course was uneventful. PMID- 26157658 TI - Spontaneous splenic rupture due to uremic coagulopathy and mortal sepsis after splenectomy. AB - Nontraumatic spontaneous splenic rupture (NSSR) has been encountered much more rarely compared with the traumatic splenic rupture. Although NSSR generally emerges in dialysis patients on account of such causes as the use of heparin during hemodialysis, uremic coagulopathy, infections, and secondary amyloidosis. Herein, we aimed to present a case of spontaneous splenic rupture which had developed soon after the inclusion of the case suffering from end-stage renal disease in routine hemodialysis program in the absence of any trauma or other prespecified risk factors for splenic rupture. A 55-year-old male patient was admitted to our hospital to have the ureteral double J stent removed. The operation was completed without any complication. Complaining an abdominal pain more prominent in the left upper abdominal quadrant in the first postoperative day, the patient underwent a through physical examination which disclosed abdominal distension, widespread tenderness, and rebound and defense positivity. The abdominal tomography depicted 122 * 114 * 95 mm lesion compatible with a hematoma. On the basis of these findings, an emergency exploratory operation was decided to be performed. Following clearance of the retroperitoneal hematoma, splenectomy was implemented. Experiencing progressive deterioration in his clinical status despite antibiotherapy, the patient unfortunately died of sepsis with multiorgan failure on the 25(th) postoperative day. In conclusion, NSSR is such an entity that may be missed out, can pursue variable clinical courses, and requires emergency therapy upon definitive diagnosis. The possibility of spontaneous bleedings should be kept in mind in any case with the history of hyperuricemia even in the absence of overt trauma, no matter if they are included in routine hemodialysis or not. PMID- 26157659 TI - Metronidazole encephalopathy: Uncommon reaction to a common drug. AB - Encephalopathy associated with metronidazole administration is an uncommon but potentially reversible disease and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. We present a case as well as a review of the literature regarding this rare but serious adverse event. PMID- 26157660 TI - Pulmonary leukostasis with severe respiratory impairment as a debut of acute myeloid leukemia. AB - We report the case of a woman, with severe respiratory impairment as a debut of acute myeloid leukemia who suspecting a pulmonary leukostasis, leukoapheresis was applied. PMID- 26157661 TI - Urine sodium changes a comparison between ill-starved and healthy children. PMID- 26157662 TI - A difficult extubation: Endotracheal tube ensnarement by a Kirschner wire. PMID- 26157663 TI - Sickle cell trait at high altitude. PMID- 26157664 TI - Comparison between transthoracic and transesophageal echocardiogram in the diagnosis of endocarditis: A retrospective analysis. PMID- 26157665 TI - Spontaneous fracture of sternum secondary to forceful coughing: A case report. PMID- 26157667 TI - Parents' Subjective Assessment of Effects of Antiepileptic Drug Discontinuation. AB - BACKGROUND AND PURPOSE: Many parents express worries about potential negative side effects of antiepileptic drugs (AED) on cognition, behavior, mood, and academic achievement. We aimed to evaluate parents' subjective feelings about cognitive or behavioral changes in their children and their quality of life after antiepileptic drug (AED) discontinuation. METHODS: A modified questionnaire based on the Korean-Quality of Life in Childhood Epilepsy and the Korean-Child Behavior Checklist was answered by parents whose children were seizure-free over the course of 1 month after AED discontinuation. All children were seizure-free for at least 2 years before AED withdrawal. RESULTS: Fifty-eight eligible patients (mean age, 14.1 +/- 4.5 years) were examined. Except valproate in cognition (p = 0.03), parents did not feel significant change after discontinuation of different drugs. They felt improvement of behavior in generalized epilepsy (p = 0.04) and better quality of life in children less than 6 year of age at diagnosis of epilepsy (p = 0.02). CONCLUSIONS: We propose that factors such as earlier age at diagnosis of epilepsy or type of epilepsy might influence parents' subjective feelings about their children's well-being after drug discontinuation, rather than the drug itself. PMID- 26157666 TI - Pharmacoresistant Epilepsy: A Current Update on Non-Conventional Pharmacological and Non-Pharmacological Interventions. AB - Uncontrolled seizure or epilepsy is intricately related with an increase risk of pharmacoresistant epilepsy. The failure to achieve seizure control with the first or second drug trial of an anticonvulsant medication given at the appropriate daily dosage is termed as pharmacoresistance, despite the fact that these drugs possess different modes of action. It is one of the devastating neurological disorders act as major culprit of mortality in developed as well as developing countries with towering prevalence. Indeed, the presence of several anti epileptic drug including carbamazepine, phenytoin, valproate, gabapentin etc. But no promising therapeutic remedies available to manage pharmacoresistance in the present clinical scenario. Hence, utility of alternative strategies in management of resistance epilepsy is increased which further possible by continuing developing of promising therapeutic interventions to manage this insidious condition adequately. Strategies include add on therapy with adenosine, verapamil etc or ketogenic diet, vagus nerve stimulation, focal cooling or standard drugs in combinations have shown some promising results. In this review we will shed light on the current pharmacological and non pharmacological mediator with their potential pleiotropic action on pharmacoresistant epilepsy. PMID- 26157668 TI - Evaluation of Short-term Mortality of Status Epilepticus and Its Risk Factors. AB - BACKGROUND AND PURPOSE: Status epilepticus (SE) is defined as epileptic seizures of greater than five minutes or more than one seizure within a five minute period without returning to normal consciousness between them. It is a life-threatening condition particularly if treatment is delayed. Previous studies reported age, duration and etiology of SE as primary determinants of mortality. METHODS: This prospective cross-sectional study performed on the patients with status epilepticus admitted in Rasoul-e-Akram hospital in Tehran. Patients followed at 30th day after SE to assess their living status. RESULTS: Sixty-five patients, (56.9% was male) with 15 to 88 years of age entered the study. Mean duration of SE was 40 minutes and for hospital stay was 7 days. 84.6% of patients responded to treatment and 11 patients (16.9%) died within 30 days after SE. Mortality rate in patients with refractory SE was 70%. Mean interval between SE and death was 11.9 +/- 11.7 days. Age, duration of SE and hospital stay, history of head trauma and neurosurgery were not predictors of mortality. Negative history for epilepsy had significantly higher mortality rate. Anoxic encephalopathy increased the mortality rate and response to treatment decreased it. CONCLUSIONS: Short-term mortality rate of SE was comparable with most of the previous reports Since our hospital has equipped emergency department, resuscitation and primary treatment of SE is usually start soon, percentage of anoxic encephalopathy is decreased and lower mortality rate is expected. We conclude that early treatment by decrease chance of anoxic encephalopathy, has significant role in outcome of SE. PMID- 26157669 TI - Anti-NMDA Receptor Antibody Encephalitis Presenting with Unilateral Non convulsive Status Epilepticus in a Male Patient. AB - Anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis is an autoimmune antibody encephalitis with psychiatric symptoms, memory disturbances, seizures and abnormal movements. It is more common in young women. We report a young man diagnosed as anti-NMDA receptor antibody encephalitis and presenting with confusion due to non-convulsive status epilepticus involving unilateral hemisphere. PMID- 26157670 TI - A Case of Hyperventilation Syndrome Mimicking Complex Partial Seizure: Usefulness of EEG Monitoring in Emergency Department. AB - Acute hyperventilation syndrome not only can be clinically misdiagnosed as epileptic seizures, but also complex partial seizures may involve hyperventilation as a part of aura. Although electrography (EEG) monitoring is one of the most important procedure to differentiate these conditions, it could not be widely used in emergency department. Variety forms of epileptic attack, mainly idiopathic generalized epilepsy, are provoked by voluntary hyperventilation. In contrast, it is not clear whether hyperventilation can activate the partial seizures. We reported a case of acute hyperventilation syndrome (HSV) mimicking first onset complex partial seizure, impending non convulsive status epilepticus, which was diagnosed by EEG in the emergency department. The electrographic seizure was provoked again by voluntary hyperventilation after clinical improvement. PMID- 26157671 TI - Seizures Related to Vitamin B6 Deficiency in Adults. AB - Vitamin B6 is closely associated with functions of the nervous, immune, and endocrine systems. Its deficiency may result in neurological disorders including convulsions and epileptic encephalopathy. Until today, this has only been reported in infants, children, and critically ill adult patients. We report a case of a 36year-old man with chronic alcoholism who presented with seizures after gastrointestinal disturbance. His seizures persisted even after treatment with antiepileptic drugs, but eventually disappeared after administration of pyridoxine. Hence, vitamin B6 deficiency may cause seizures in adult patients with chronic alcoholism. PMID- 26157672 TI - Mesial Temporal Lobe Epilepsy in Congenital Toxoplasmosis: A Case Report. AB - Toxoplasmosis is a rare disease caused by intracellular protozoan parasite, Toxoplasma gondii. Though most patients with toxoplasmosis are asymptomatic, congenital toxoplasmosis in the fetus can cause ocular involvement such as chorioretinitis and central nervous system disease including intracerebral calcification, nystagmus, hydrocephalus and microcephaly. Also, these brain lesions can cause seizure secondarily. Our patient was diagnosed with congenital toxoplasmosis, based on toxoplasma-specific serologic test with typical clinical symptoms, including chorioretinitis, nystagmus, hydrocephalus and cerebral palsy. Her brain imaging findings revealed not only the multifocal encephalomalacia, but also multifocal cerebral calcification including intracerebral calcification in left perihippocampal region. Her epileptogenic zone was defined as mesial temporal lobe including hippocampus on left side by seizure semiology, electroencephalogram and neuroimaging including single photon emission computed tomography and 18F-Fluorodeoxyglucose positron-emission tomography. Her seizures were refractory to multiple anti-epileptic drugs. We report a patient with congenital toxoplasmosis who showed intractable mesial temporal lobe epilepsy. PMID- 26157673 TI - Anti-NMDA Receptor Encephalitis in a Pregnant Woman. AB - Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is one of the most common types of autoimmune synaptic encephalitis. Anti-NMDA receptor encephalitis commonly occurs in young women with ovarian teratoma. It has variable clinical manifestations and treatment responses. Sometimes it is misdiagnosed as a psychiatric disorder or viral encephalitis. To the best of our knowledge, anti NMDA receptor encephalitis is a rare condition in pregnant women. We report a case of anti-NMDA receptor encephalitis in a pregnant woman who presented with abnormal behavior, epileptic seizure, and hypoventilation. PMID- 26157674 TI - Stereotactic radiotherapy for early stage non-small cell lung cancer. AB - Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice. PMID- 26157675 TI - The protective effects of trace elements against side effects induced by ionizing radiation. AB - Trace elements play crucial role in the maintenance of genome stability in the cells. Many endogenous defense enzymes are containing trace elements such as superoxide dismutase and metalloproteins. These enzymes are contributing in the detoxification of reactive oxidative species (ROS) induced by ionizing radiation in the cells. Zinc, copper, manganese, and selenium are main trace elements that have protective roles against radiation-induced DNA damages. Trace elements in the free salt forms have protective effect against cell toxicity induced by oxidative stress, metal-complex are more active in the attenuation of ROS particularly through superoxide dismutase mimetic activity. Manganese-complexes in protection of normal cell against radiation without any protective effect on cancer cells are more interesting compounds in this topic. The aim of this paper to review the role of trace elements in protection cells against genotoxicity and side effects induced by ionizing radiation. PMID- 26157676 TI - Multi-institutional analysis of T3 subtypes and adjuvant radiotherapy effects in resected T3N0 non-small cell lung cancer patients. AB - PURPOSE: We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse. RESULTS: The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively). CONCLUSION: The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC. PMID- 26157677 TI - Can we omit prophylactic inguinal nodal irradiation in anal cancer patients? AB - PURPOSE: To evaluate the appropriateness of prophylactic inguinal nodal irradiation (PINI), we analyzed patterns of failure in anal cancer patients who were inguinal node-negative at presentation and did not receive PINI. MATERIALS AND METHODS: We retrospectively reviewed the records of 33 anal cancer patients treated by definitive concurrent chemoradiation therapy (CCRT) between 1994 and 2013. Radiotherapy consisted of a total dose of 44-45 Gy (22-25 fractions in 5 weeks) on the whole pelvis, anus, and perineum. Except inguinal lymphadenopathy was present at initial diagnosis, the entire inguinal chain was not included in the radiation field. In other words, there was no PINI. RESULTS: The median follow-up duration was 50 months (range, 4 to 218 months). Median survival and progression-free survival (PFS) were 57 months (range, 10 to 218 months) and 50 months (range, 4 to 218 months), respectively. Among the survival, the median follow-up duration was 51 months (range, 12 to 218 months). The 5-year overall survival and PFS rates were 93.4% and 88.8%, respectively. Although none of the patients received inguinal node irradiation for prophylactic purposes, there was no inguinal recurrence. CONCLUSION: Treatment of anal cancer by omitting PINI might be considered in selected patients with clinically uninvolved inguinal nodes. PMID- 26157678 TI - Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer. AB - PURPOSE: To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). MATERIALS AND METHODS: From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. RESULTS: The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. CONCLUSION: The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication. PMID- 26157679 TI - Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy. AB - PURPOSE: The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. MATERIALS AND METHODS: Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. RESULTS: With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CONCLUSION: CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy related mucositis. The results of ongoing trials are awaited. PMID- 26157680 TI - Prognostic analysis of uterine cervical cancer treated with postoperative radiotherapy: importance of positive or close parametrial resection margin. AB - PURPOSE: To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute. MATERIALS AND METHODS: Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox regression was applied to analyze prognostic factors. RESULTS: The 5-year disease free survival was 79% and 5-year OS was 91%. In univariate analysis, positive or close PRM, LN metastasis, direct extension of parametrium, lymphovascular invasion, histology of adenocarcinoma, and chemotherapy were related with more DM and poor OS. In multivariate analysis, PRM and LN metastasis remained independent prognostic factors for OS. CONCLUSION: PORT after radical hysterectomy in uterine cervical cancer showed excellent OS in this study. Positive or close PRM after radical hysterectomy in uterine cervical cancer correlates with poor prognosis even with CCRT. Therefore, additional treatments to improve local control such as radiation boosting need to be considered. PMID- 26157681 TI - Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer. AB - PURPOSE: To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). MATERIALS AND METHODS: We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). RESULTS: With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. CONCLUSION: ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT. PMID- 26157682 TI - Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer. AB - PURPOSE: To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. RESULTS: The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. CONCLUSION: Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance in early uterine cervical cancer patients. More effective systemic treatments might be needed to reduce distant metastasis in these patients. PMID- 26157683 TI - Morphologic change of rectosigmoid colon using belly board and distended bladder protocol. AB - PURPOSE: This study investigates morphologic change of the rectosigmoid colon using a belly board in prone position and distended bladder in patients with rectal cancer. We evaluate the possibility of excluding the proximal margin of anastomosis from the radiation field by straightening the rectosigmoid colon. MATERIALS AND METHODS: Nineteen patients who received preoperative radiotherapy between 2006 and 2009 underwent simulation in a prone position (group A). These patients were compared to 19 patients treated using a belly board in prone position and a distended bladder protocol (group B). Rectosigmoid colon in the pelvic cavity was delineated on planning computed tomography (CT) images. A total dose of 45 Gy was planned for the whole pelvic field with superior margin of the sacral promontory. The volume and redundancy of rectosigmoid colon was assessed. RESULTS: Patients in group B had straighter rectosigmoid colons than those in group A (no redundancy; group A vs. group B, 10% vs. 42%; p = 0.03). The volume of rectosigmoid colon in the radiation field was significantly larger in group A (56.7 vs. 49.1 mL; p = 0.009). In dose volume histogram analysis, the mean irradiated volume was lower in patients in group B (V45 27.2 vs. 18.2 mL; p = 0.004). In Pearson correlation coefficient analysis, the in-field volume of rectosigmoid colon was significantly correlated with the bladder volume (R = 0.86, p = 0.003). CONCLUSION: Use of a belly board and distended bladder protocol could contribute to exclusion of the proximal margin of anastomosis from the radiation field. PMID- 26157684 TI - Development of new on-line statistical program for the Korean Society for Radiation Oncology. AB - PURPOSE: To develop new on-line statistical program for the Korean Society for Radiation Oncology (KOSRO) to collect and extract medical data in radiation oncology more efficiently. MATERIALS AND METHODS: The statistical program is a web-based program. The directory was placed in a sub-folder of the homepage of KOSRO and its web address is http://www.kosro.or.kr/asda. The operating systems server is Linux and the webserver is the Apache HTTP server. For database (DB) server, MySQL is adopted and dedicated scripting language is the PHP. Each ID and password are controlled independently and all screen pages for data input or analysis are made to be friendly to users. Scroll-down menu is actively used for the convenience of user and the consistence of data analysis. RESULTS: Year of data is one of top categories and main topics include human resource, equipment, clinical statistics, specialized treatment and research achievement. Each topic or category has several subcategorized topics. Real-time on-line report of analysis is produced immediately after entering each data and the administrator is able to monitor status of data input of each hospital. Backup of data as spread sheets can be accessed by the administrator and be used for academic works by any members of the KOSRO. CONCLUSION: The new on-line statistical program was developed to collect data from nationwide departments of radiation oncology. Intuitive screen and consistent input structure are expected to promote entering data of member hospitals and annual statistics should be a cornerstone of advance in radiation oncology. PMID- 26157685 TI - Exome sequencing in a breast cancer family without BRCA mutation. AB - PURPOSE: We performed exome sequencing in a breast cancer family without BRCA mutations. MATERIALS AND METHODS: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members. RESULTS: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined. CONCLUSION: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies. PMID- 26157686 TI - The using of megavoltage computed tomography in image-guided brachytherapy for cervical cancer: a case report. AB - We present a case of cervical cancer treated by concurrent chemoradiation. In radiation therapy part, the combination of the whole pelvic helical tomotherapy plus image-guided brachytherapy with megavoltage computed tomography of helical tomotherapy was performed. We propose this therapeutic approach could be considered in a curative setting in some problematic situation as our institution. PMID- 26157687 TI - Transsylvian-Transinsular Approach for Deep-Seated Basal Ganglia Hemorrhage: An Experience at a Single Institution. AB - OBJECTIVE: Treatment of spontaneous intracerebral hemorrhage (ICH) remains controversial. However, an extensive hemorrhage with a poor mental status is suitable for surgical evacuation. Our experience with the transsylvian transinsular (TS-TI) microsurgical approach for deep-seated basal ganglia (BG) ICH was investigated. MATERIAL AND METHODS: A retrospective review was conducted on 86 patients with BG ICH who underwent an operation at the Department of Neurosurgery of our Hospital from September 2011 to October 2014. Thirteen patients underwent craniotomy and the TS-TI microsurgical approach for hematoma evacuation. Twenty-seven patients underwent conventional craniotomy with the trans-cortical transtemporal (TC-TT) approach, and 46 patients underwent a burrhole operation and hematoma drainage using a frameless stereotaxic device (ST). RESULTS: The average age distribution was similar. The preoperative Glasgow coma scale (GCS) was similar for the TC-TT and TS-TI groups. The pre-operative hematoma levels were higher in the TC-TT (109.4 +/- 48.6 mL) and TS-TI (96.0 +/- 39.0 mL) groups than in the ST group (46.5 +/- 23.5 mL). The hematoma removal rate was 77% in the TC-TT group, 88% in the TS-TI group, and 34% in the ST group. The mean maintenance period of a hematoma catheter was 3.6 days in the ST group. The clinical outcome showed correlation with the preoperative neurological symptoms. CONCLUSION: The TS-TI group was superior to the TC-TT group for evacuation of an intracerebral hematoma. PMID- 26157688 TI - A Simple Method for Reconstruction of the Temporalis Muscle Using Contourable Strut Plate after Pterional Craniotomy: Introduction of the Surgical Techniques and Analysis of Its Efficacy. AB - OBJECTIVE: Pterional craniotomy (PC) using myocutaneous (MC) flap is a simple and efficient technique; however, due to subsequent inferior displacement (ID) of the temporalis muscle, it can cause postoperative deformities of the muscle such as depression along the inferior margin of the temporal line of the frontal bone (DTL) and muscular protrusion at the inferior portion of the temporal fossa (PITF). Herein, we introduce a simple method for reconstruction of the temporalis muscle using a contourable strut plate (CSP) and evaluate its efficacy. MATERIALS AND METHODS: Patients at follow-ups between January 2014 and October 2014 after PCs were enrolled in this study. Their postoperative deformities of the temporalis muscle including ID, DTL, and PITF were evaluated. These PC cases using MC flap were classified according to two groups; one with conventional technique without CSP (MC Only) and another with reconstruction of the temporalis muscle using CSP (MC + CSP). Statistical analyses were performed for comparison between the two groups. RESULTS: Lower incidences of ID of the muscle (p < 0.001), DTL (p < 0.001), and PITF (p = 0.001) were observed in the MC + CSP than in the MC Only group. The incidence of acceptable outcome was markedly higher in the MC + CSP group (p < 0.001). ID was regarded as a causative factor for DTL and PITF (p < 0.001 in both). CONCLUSION: Reconstruction of the temporalis muscle using CSP after MC flap is a simple and efficient technique, which provides an outstanding outcome in terms of anatomical restoration of the temporalis muscle. PMID- 26157689 TI - A Protocol-Based Decision for Choosing a Proper Surgical Treatment Option for Carotid Artery Stenosis. AB - OBJECTIVE: There are two established surgical treatment options for carotid artery stenosis. Carotid endarterectomy (CEA) has been accepted as a gold standard for surgical treatment while carotid artery stenting (CAS) has recently become an alternative option. Each treatment option has advantages and disadvantages for the treatment outcomes. We propose a protocol for selection of a proper surgical treatment option for carotid artery stenosis. MATERIALS AND METHODS: A total of 192 published articles on management of carotid artery stenosis were reviewed. Preoperatively considerable factors which had been repeatedly noted in those articles for the risk/benefits of CEA or CAS were selected. According to those factors, a protocol with four categories was established. RESULTS: CEA or CAS is indicated when the patient has a symptomatic stenosis >= 50%, or when the patient has an asymptomatic stenosis >= 80%. Each treatment option has absolute indications and favorable indications. Each absolute indication is scored with three points, and each favorable indication, one point. Based on the highest scores, a proper treatment option (CEA or CAS) is selected. CONCLUSION: We have been treating patients according to this protocol and evaluating the outcomes of our protocol-based decision because this protocol might be helpful in assessment of risk/benefit for selection of a proper surgical treatment option in patients with carotid artery stenosis. PMID- 26157690 TI - Endovascular Treatment in Ruptured Middle Cerebral Artery Dissection Preservation of Arterial Continuity. AB - Rupture of spontaneous dissecting aneurysms of the middle cerebral artery (MCA) is rare and its etiology remains obscure, although the risk of rebleeding is greater than with saccular aneurysms. Most reports concerning the treatment of a ruptured dissecting aneurysm of the anterior circulation involve surgical trapping or wrapping. Here, we report on a case of an MCA dissecting rupture treated with endovascular procedures. A 22-year-old female presented with sudden stuporous mental change following severe headache and left side hemiparesis. A computed tomography scan showed a diffuse subarachnoid hemorrhage and diffusion MR showed diffusion restriction at the right putamen and internal capsule. A 3 hour follow-up digital subtraction angiography (DSA) showed a dissecting aneurysm, which was not seen on an initial DSA. A stent assisted coil embolization was performed and double stents were applied to achieve flow diversion effects. A small remnant area of the dissecting aneurysm had disappeared at 60-day and was not observed on 12-month follow-up DSA. PMID- 26157691 TI - Seven Intracranial Aneurysms in One Patient: Treatment and Review of Literature. AB - Before the advent of endovascular coiling, patients with multiple intracranial aneurysms were treated with surgical clipping; however, with the advancements in endovascular technology, intracranial aneurysms can be treated with surgical clipping and/or endovascular coiling. We describe a case of subarachnoid hemorrhage in a patient with 7 intracranial aneurysms. A 45-year-old female developed a sudden headache and left sided hemiparesis. Initial workup showed a subarachnoid hemorrhage in the right Sylvian fissure. Further angiographic workup showed 7 intracranial aneurysms (left and right middle cerebral artery bifurcation, right middle cerebral artery, anterior communicating artery, left posterior communicating artery, right posterior inferior cerebellar artery, and left superior cerebellar artery). The patient underwent two craniotomies for surgical clipping of the anterior circulation aneurysms and endovascular stent assisted coils for the posterior circulation aneurysms. The need for anti platelet agents for endovascular treatment of the posterior circulation aneurysms and clinical presentation warranted surgical clipping of the anterior circulation aneurysms prior to endovascular therapy. We describe a case report and decision making for a patient with multiple intracranial aneurysms treated with surgical clipping and endovascular coiling. PMID- 26157692 TI - Characteristics of Pediatric Pancreatitis on Magnetic Resonance Cholangiopancreatography. AB - Pediatric pancreatitis is not uncommon and results in considerable morbidity and mortality in the affected children. Unlike adults, pediatric pancreatitis is more frequently associated with underlying structural abnormalities, trauma, and drugs rather than an idiopathic etiology. Magnetic resonance cholangiopancreatography (MRCP) is a good imaging modality for evaluating pancreatitis and determining etiology without exposure to radiation. This article focuses on MRCP findings associated with various causes of pancreatitis in children, particularly structural abnormalities of the pancreaticobiliary system, as well as describing the feasibility, limitations, and solutions associated with pediatric MRCP. PMID- 26157693 TI - Differences in Clinical and Laboratory Findings between Group D and Non-Group D Non-Typhoidal Salmonella Gastroenteritis in Children. AB - PURPOSE: To investigate the differences in clinical features and laboratory findings between group D and non-group D non-typhoidal Salmonella (NTS) gastroenteritis in children. METHODS: A retrospective chart review of children diagnosed with NTS confirmed by culture study was performed. The clinical features and laboratory findings of group D and non-group D NTS were compared. RESULTS: From 2003 to 2012, 75 cases were diagnosed as NTS at our center. The number of group D and non-group D patients was 45 and 30, respectively. The mean age was higher in group D than in non-group D patients (5.1 years vs. 3.4 years, p=0.038). Headaches were more frequently observed (p=0.046) and hematochezia was less frequently observed (p=0.017) in group D than in non-group D NTS gastroenteritis patients. A positive Widal test result was observed in 53.3% of group D and 6.7% of non-group D NTS cases (O-titer, p=0.030; H-titer, p=0.039). There were no differences in white blood cell counts, level of C-reactive protein and rate of antimicrobial resistance between group D and non-group D cases. CONCLUSION: The more severe clinical features such as headache, fever, and higher Widal titers were found to be indicative of group D NTS gastroenteritis. Additionally, group D NTS gastroenteritis was more commonly found in older patients. Therefore, old age, fever, headache, and a positive Widal test are more indicative of group D NTS than non-group D NTS gastroenteritis. Pathophysiological mechanisms may differ across serologic groups. PMID- 26157694 TI - Benefits of a Dedicated Breastfeeding Facility and Support Program for Exclusive Breastfeeding among Workers in Indonesia. AB - PURPOSE: A mother's working environment is believed to be a major determinant of exclusive breastfeeding (EBF) practice. We aimed to define the influence of a facility dedicated to breastfeeding and a breastfeeding support program at the workplace on breastfeeding practice. METHODS: A cross-sectional study was performed in five workplaces. The inclusion criteria were female workers whose last child was between 6 and 36 months old. Observational data were obtained and a questionnaire was filled out. The World Health Organization definition for EBF was used. RESULTS: Data from 186 subjects (74 office workers and 112 factory workers) were collected. Just over half (52%) of the mothers were between 20 and 46 years old, 75.3% had graduated from high school and university, 12.9% had more than two children and 36.0% owned a house. The prevalence of EBF during the last 6 months was 32.3%. A proper dedicated breastfeeding facility was available for 21.5% of the mothers, but only 7.5% had been in contact with a breastfeeding support program. The presence of a dedicated breastfeeding facility increased EBF practice almost threefold, by an odds ratio (OR) of 2.74 and a 95% confidence interval (CI) of 1.34-5.64 (p<0.05). Knowledge of the breastfeeding support program increased EBF practice by almost six times (OR, 5.93; 95% CI, 1.78-19.79) (p<0.05). CONCLUSION: Our findings suggest that Governments should make it obligatory for employers to offer a breastfeeding support program and a dedicated breastfeeding facility at the workplace as these simple measures significantly increase EBF. PMID- 26157695 TI - The Iron Status of Very Low Birth Weight Infants Receiving Multiple Erythrocyte Transfusions during Hospitalization in the Neonatal Intensive Care Unit. AB - PURPOSE: We investigated the iron status of very low birth weight infants receiving multiple erythrocyte transfusions during hospitalization in the neonatal intensive care unit (NICU). METHODS: We enrolled 46 very low birth weight infants who were admitted to the Kyungpook National University Hospital between January 2012 and December 2013. Serum ferritin was measured on their first day of life and weekly thereafter. We collected individual data of the frequency and volume of erythrocyte transfusion and the amount of iron intake. RESULTS: A total of 38 (82.6%) of very low birth weight infants received a mean volume of 99.3+/-93.5 mL of erythrocyte transfusions in NICU. The minimum and maximum serum ferritin levels during hospitalization were 146.2+/-114.9 ng/mL and 456.7+/-361.9 ng/mL, respectively. The total volume of erythrocyte transfusion was not correlated to maximum serum ferritin concentrations after controlling for the amount of iron intake (r=0.012, p=0.945). Non-transfused infants took significantly higher iron intake compared to infants receiving >=100 mL/kg erythrocyte transfusion (p<0.001). Minimum and maximum serum ferritin levels of non-transfused infants were higher than those of infants receiving <100 mL/kg erythrocyte transfusions (p=0.026 and p=0.022, respectively). Infants with morbidity including bronchopulmonary dysplasia or retinopathy of prematurity received a significantly higher volume of erythrocyte transfusions compared to infants without morbidity (p<0.001). CONCLUSION: Very low birth weight infants undergoing multiply erythrocyte transfusions had excessive iron stores and non transfused infants also might had a risk of iron overload during hospitalization in the NICU. PMID- 26157696 TI - Abdominal Subcutaneous Fat Thickness Measured by Ultrasonography Correlates with Hyperlipidemia and Steatohepatitis in Obese Children. AB - PURPOSE: The aim of this study is to evaluate the relationship between abdominal subcutaneous fat thickness measured by ultrasonography (US) and serum lipid profile and liver transaminases in obese children. METHODS: One hundred and sixty six children diagnosed with obesity from May 2001 to December 2013 were included in this study. Data on serum lipid profile and liver transaminases were collected from clinical records. Abdominal subcutaneous fat thickness and grade of hepatic steatosis were evaluated by US. RESULTS: Of the 166 children, 107 were diagnosed with hepatic steatosis by US, 46 with grade I, 56 with grade II, and five children with grade III. According to the grade of hepatic steasosis, the average values of midline abdominal subcutaneous fat thickness and right flank abdominal subcutaneous fat thickness measured 2.9+/-0.8 cm and 1.9+/-0.7 cm in the normal group, 3.3+/-0.8 cm and 2.0+/-0.7 cm in grade I, 3.8+/-0.8 cm and 2.3+/-0.8 cm in grade II, and 4.1+/-0.8 cm and 2.8+/-1.4 cm in grade III, respectively. Abdominal subcutaneous fat thickness correlated with grade of hepatic steatosis (p<0.01). In addition, abdominal subcutaneous fat thickness correlated with concentration of serum lipids and liver transaminases in the age group of 12-14 years (p<0.01). CONCLUSION: Abdominal subcutaneous fat thickness measured by US can be used as a reliable predictor of possible hyperlipidemia and steatohepatitis in children, especially during the adolescent stage. PMID- 26157697 TI - Pediatric Cholecystectomy: Clinical Significance of Cases Unrelated to Hematologic Disorders. AB - PURPOSE: Cholecystectomy is rarely performed in the child and adolescent. However, it is associated with several conditions. This study was conducted to describe the characteristics of pediatric patient who underwent cholecystectomy unrelated to hematologic disorders, and then to suggest its clinical significance in management by comparing a simple and complicated gallbladder disease. METHODS: We reviewed cases of cholecystectomy in pediatric patients (under 18 years old) at a single institution between January 2003 and October 2014. There were 143 cases during the study period and 24 were selected as the subject group. RESULTS: There were 7 male (29.2%) and 17 female (70.8%) patients. The mean age was 13.1 years old, and 66.6% of patients were older than 12 years. Mean body weight was 52.7 kg, and body mass index was 21.7 kg/m(2), with 41.7% of patients being overweight or obese. We could identify a female predominance and high proportion of overweight or obesity in a complicated disease. There were also significantly increased levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin in this group. Most patients (87.5%) underwent laparoscopic cholecystectomy. CONCLUSION: Cholecystectomy for diseases unrelated to hematologic disorders is rarely performed in the child and adolescent. In general, female patients who are overweight or obese, and those older than 12 years old, require laparoscopic cholecystectomy owing to multiple gallstones. This condition has a tendency to show a complicated gallbladder disease and significantly increased levels of AST, ALT, ALP, and bilirubin. PMID- 26157698 TI - Wilson's Disease in Bangladeshi Children: Analysis of 100 Cases. AB - PURPOSE: To evaluate clinical and laboratory profile of Wilson's disease (WD) in children. METHODS: This cross sectional study was conducted at Bangabandhu Sheikh Mujib Medical University Hospital. Bangladesh, over a period of 3 years. One hundred consecutive children of WD between 3 to 18 years of age were evaluated. RESULTS: Mean age was 8.5+/-1.5 years. Male female ratio was 2:1. Ninety-one percent of patients were Muslim and 9% Hindu. A total of 53% cases of hepatic WD presented between 5 to 10 years of age and most of the neurologic WD manifested in 10-15 years age group. Sixty-nine children presented only with hepatic manifestations, 6 only with neurological manifestations, 14 with both hepatic and neurological manifestation, 10 children was asymptomatic and 1 patient presented with psychiatric features. WD presented as chronic liver disease (CLD) in 42%, CLD with portal hypertension in 34%, acute hepatitis in 20% and fulminant hepatic failure in 4% cases. Stigmata of CLD were found in 18% patients. Keiser Fleischser ring was found in 76% total patients. Elevated serum transaminase was found in 85% cases, prolonged prothrombin time in 59% cases and hypoalbuminaemia in 53% cases. A total of 73% patients had low serum ceruloplasmin, basal urinary copper of >100 ug/day was found in 81% cases and urinary copper following penicillamine challenge of >1,200 ug/day was found in 92% cases. CONCLUSION: Majority of studied WD children presented with hepatic manifestation of which 76% presented with CLD. Any child presented with jaundice after the age of 3 years should be investigated for WD. PMID- 26157699 TI - A Case of Visceral Autonomic Neuropathy Complicated by Guillain-Barre Syndrome Accompanied with Cyclic Vomiting Syndrome-like Disorder in a Child. AB - We present a case of an 8-year-old boy with visceral autonomic neuropathy complicated by Guillain-Barre syndrome. In this pediatric patient, gastroparesis was the major symptom among the autonomic symptoms. Due to the gastroparesis, there was no progress with the oral diet, and nutrition was therefore supplied through a nasojejunal tube and gastrojejunal tube via Percutaneous endoscopic gastrostomy (PEG). After tube feeding for 9 months, the patient's gastrointestinal symptoms improved and his oral ingestion increased. The pediatric patient was maintained well without gastrointestinal symptoms for 3 months after removal of the PEG, had repeated vomiting episodes which lead to the suspicion of cyclic vomiting syndrome. Then he started treatment with low-dose amitriptyline, which resulted in improvement. Currently, the patient has been maintained well for 6 months without recurrence, and his present growth status is normal. PMID- 26157700 TI - A Case of Intussusception with Acute Appendicitis. AB - In children presenting to hospital with gastrointestinal symptoms, diseases such as intussusception and acute appendicitis require particular attention and careful examination. Early diagnosis and proper treatment are important because of possible severe complications such as peritonitis and death. Intussusception and appendicitis share similar clinical manifestations. More importantly, the presence of acute appendicitis together with intussusception in children is very rare. We describe an interesting case of a 38-month-old boy who presented with abdominal pain in the right lower quadrant. His vital signs were stable and laboratory test findings showed no specific alterations. We detected tenderness in the right lower quadrant. A computed tomography scan showed an ileocolic intussusception with no strangulation and diffuse wall thickening of the appendix trapped within the intussusception. The patient underwent an appendectomy and manual reduction. PMID- 26157701 TI - Clinical, Biochemical, and Genetic Characterization of Glycogen Storage Type IX in a Child with Asymptomatic Hepatomegaly. AB - Glycogen storage disease type IX (GSD IX) is caused by a defect in phosphorylase b kinase (PhK) that results from mutations in the PHKA2, PHKB, and PHKG2 genes. Patients usually manifest recurrent ketotic hypoglycemia with growth delay, but some may present simple hepatomegaly. Although GSD IX is one of the most common causes of GSDs, its biochemical and genetic diagnosis has been problematic due to its rarity, phenotypic overlap with other types of GSDs, and genetic heterogeneities. In our report, a 22-month-old boy with GSD IX is described. No other manifestations were evident except for hepatomegaly. His growth and development also have been proceeding normally. Diagnosed was made by histologic examination, an enzyme assay, and genetic testing with known c.3210_3212del (p.Arg1070del) mutation in PHKA2 gene. PMID- 26157702 TI - Atypical beta-Catenin Activated Child Hepatocellular Tumor. AB - Hepatocellular adenomas are a benign, focal, hepatic neoplasm that have been divided into four subtypes according to the genetic and pathological features. The beta-catenin activated subtype accounts for 10-15% of all hepatocellular adenomas and specific magnetic resonance imaging features have been defined for different hepatocellular adenomas subtypes. The current study aimed to report the magnetic resonance imaging features of a well differentiated hepatocellular carcinoma that developed on the basis of beta-catenin activated hepatocellular adenomas in a child. In this case, atypical diffuse steatosis was determined in the lesion. In the literature, diffuse steatosis, which is defined as a feature of the hepatocyte nuclear factor-1alpha-inactivated hepatocellular adenomas subtype, has not been previously reported in any beta-catenin activated hepatocellular adenomas case. Interlacing magnetic resonance imaging findings between subtypes show that there are still many mysteries about this topic and larger studies are warranted. PMID- 26157703 TI - Esophagus and Contralateral Lung-Sparing IMRT for Locally Advanced Lung Cancer in the Community Hospital Setting. AB - BACKGROUND: The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue-sparing IMRT can allow safe dose escalation resulting in decreased acute and late toxicity. METHODS: We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of three dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT). From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity, and overall survival. RESULTS: Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 vs. 60.8 Gy, p = 0.04), patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, esophageal V60, and mean esophagus doses compared to patients treated with standard RT (p <= 0.001). Patients in the normal tissue-sparing IMRT group had reduced acute grade >=3 esophagitis (0 vs. 11%, p < 0.001), acute grade >=2 weight loss (2 vs. 16%, p = 0.04), and late grade >=2 pneumonitis (7 vs. 21%, p = 0.02). The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p = 0.015). CONCLUSION: These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose-volume constraints are feasible in the community hospital setting without sacrificing disease control. PMID- 26157704 TI - Oncogenic RAS Mutants Confer Resistance of RMS13 Rhabdomyosarcoma Cells to Oxidative Stress-Induced Ferroptotic Cell Death. AB - Recent genomic studies revealed a high rate of recurrent mutations in the RAS pathway in primary rhabdomyosarcoma (RMS) samples. In the present study, we therefore investigated how oncogenic RAS mutants impinge on the regulation of cell death of RMS13 cells. Here, we report that ectopic expression of NRAS12V, KRAS12V, or HRAS12V protects RMS13 cells from oxidative stress-induced cell death. RMS13 cells engineered to express NRAS12V, KRAS12V, or HRAS12V were significantly less susceptible to loss of cell viability upon treatment with several oxidative stress inducers including the thioredoxin reductase inhibitor Auranofin, the glutathione (GSH) peroxidase 4 inhibitor RSL3 or Erastin, an inhibitor of the cysteine/glutamate amino acid transporter system [Formula: see text] that blocks GSH synthesis. Notably, addition of Ferrostatin-1 confers protection against Erastin- or RSL3-induced cytotoxicity, indicating that these compounds trigger ferroptosis, an iron-dependent form of programed cell death. Furthermore, RMS13 cells overexpressing oncogenic RAS mutants are significantly protected against the dual PI3K/mTOR inhibitor PI103, whereas they are similarly sensitive to DNA-damaging drugs such as Doxorubicin or Etoposide. This suggests that oncogenic RAS selectively modulates cell death pathways triggered by cytotoxic stimuli in RMS13 cells. In conclusion, our discovery of an increased resistance to oxidative stress imposed by oncogenic RAS mutants in RMS13 cells has important implications for the development of targeted therapies for RMS. PMID- 26157705 TI - Unfolding the Role of Stress Response Signaling in Endocrine Resistant Breast Cancers. AB - The unfolded protein response (UPR) is an ancient stress response that enables a cell to manage the energetic stress that accompanies protein folding. There has been a significant recent increase in our understanding of the UPR, how it integrates physiological processes within cells, and how this integration can affect cancer cells and cell fate decisions. Recent publications have highlighted the role of UPR signaling components on mediating various cell survival pathways, cellular metabolism and bioenergenics, and autophagy. We address the role of UPR on mediating endocrine therapy resistance and estrogen receptor-positive breast cancer cell survival. PMID- 26157706 TI - Determinants in the Uptake of the Human Papillomavirus Vaccine: A Systematic Review Based on European Studies. AB - BACKGROUND: Cervical cancer is the fourth most common cancer affecting women worldwide. Since 2006, two human papillomavirus vaccines (HPVV) have been licensed to protect women against the virus that causes cervical cancer. However, worldwide coverage remains unequal. Studies from the USA found strong evidence for differences in HPVV uptake by ethnicity and healthcare coverage. As the profile of ethnic groups and the healthcare system in the USA differ from countries in Europe where HPVV is free in most of the countries, we conducted a systematic review in order to analyze the determinants of HPVV uptake in Europe. METHODS: We performed a systematic Pubmed, Scopus, and Science Direct search to find articles published from HPVV availability in European countries until April 2014. No age restriction was applied. We included all studies assessing factors associated with HPVV uptake. Uptake refers to either initiation and/or completion of the three dose vaccination program. RESULTS: Out of the 23 eligible studies, 14 were retrospective reviews of data, six were cross-sectional surveys, and three were prospective cohort studies. Higher HPVV uptake was associated with ethnic majority populations, higher socio-economic status, regular cervical screening participation by the mother, and having received previous childhood vaccinations. CONCLUSION: Since the vaccine is offered for free in most of the European countries, the findings suggest that ethno-cultural and educational factors play an important role when it comes to HPVV uptake. Girls who were undervaccinated had also a lower uptake of standard childhood vaccines and mothers who were less likely to attend cervical cancer screening. This may indicate that only few parents have specific concerns with HPVV, and that preventive health care should seek ways to target these vulnerable groups. PMID- 26157707 TI - Overexpression of Brucella putative glycosyltransferase WbkA in B. abortus RB51 leads to production of exopolysaccharide. AB - Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in mammals. Brucella strains containing the O-polysaccharide in their cell wall structure exhibit a smooth phenotype whereas the strains devoid of the polysaccharide show rough phenotype. B. abortus strain RB51 is a stable rough attenuated mutant which is used as a licensed live vaccine for bovine brucellosis. Previous studies have shown that the wboA gene, which encodes a glycosyltransferase required for the synthesis of O-polysaccharide, is disrupted in B. abortus RB51 by an IS711 element. Although complementation of strain RB51 with a functional wboA gene results in O-polysaccharide synthesis in the cytoplasm, it does not result in smooth phenotype. The aim of this study was to determine if overexpression of Brucella WbkA or WbkE, two additional putative glycosyltransferases essential for O-polysaccharide synthesis, in strain RB51 would result in the O-polysaccharide synthesis and smooth phenotype. Our results demonstrate that overexpression of wbkA or wbkE gene in RB51 does not result in O polysaccharide expression as shown by Western blotting with specific antibodies. However, wbkA, but not wbkE, overexpression leads to the development of a clumping phenotype and the production of exopolysaccharide(s) containing mannose, galactose, N-acetylglucosamine, and N-acetylgalactosamine. Moreover, we found that the clumping recombinant strain displays increased adhesion to polystyrene plates. The recombinant strain was similar to strain RB51 in its attenuation characteristic and in its ability to induce protective immunity against virulent B. abortus challenge in mice. PMID- 26157709 TI - ATP-dependent potassium channels are implicated in simvastatin pretreatment induced inhibition of apoptotic cell death after renal ischemia/reperfusion injury. AB - BACKGROUND: Simvastatin is a widely used medication in cardiac care. Here we evaluate the role of ATP sensitive potassium (KATP) channels in simvastatin induced renal protection after renal ischemia/reperfusion (I/R) injury. METHODS: A total of 81 male Wistar rats, were treated with simvastatin (10 and 20mg/kg/day; gavage, one week). Some groups received glibenclamide (KATP channel inhibitor; 5mg/kg) before ischemia (45min) and reperfusion (24h). Finally the kidneys were processed for histological analysis and measurement of biochemical parameters including tissue malondialdehyde (MDA), blood urea nitrogen (BUN), fractional excretion of sodium (FENa), creatinine clearance rate (CCr) and Bcl2 associated X protein (Bax) expression. RESULTS: IR significantly increased serum Cr (p< 0.01) and BUN levels (p< 0.01), elevated FENa (p<0.01) and tissue MDA (p<0.01), and decreased CCr (p< 0.01) and induced histological damage. Bax pro apoptotic protein was upregulated in renal tissue after I/R injury and downregulated in simvastatin pretreated group. Simvastatin at doses of 10 and 20mg/kg/day significantly reduced serum Cr and BUN levels (p< 0.05 vs. IR group), tissue MDA contents and FENa (p< 0.05 vs. I/R) and increased CCr (p< 0.05 vs. IR). Renal tissue injury was improved only in simvastatin 20mg/kg/day group (p< 0.05). Glibenclamide significantly abolished protective effects of simvastatin and increased serum Cr and BUN and FENa and decreased CCr (p< 0.05). It also abolished the effects of simvastatin on tissue injury and MDA contents and downregulated the Bax protein after IR injury (p< 0.05). CONCLUSION: Opening of KATP channels is essential for simvastatin-induced renal protection against I/R injury. PMID- 26157708 TI - Targeting metabolic disorders by natural products. AB - The most prevalent metabolic disorders are diabetes mellitus, obesity, dyslipidemia, osteoporosis and metabolic syndrome, which are developed when normal metabolic processes are disturbed. The most common pathophysiologies of the above disorders are oxidative stress, Nrf2 pathways, epigenetic, and change in miRNA expression. There is a challenge in the prevention and treatment of metabolic disorders due to severe adverse effects of some synthetic drugs, their high cost, lack of safety and poverty in some conditions, and insufficient accessibility for the general population in the world. With increasing interest in shifting from synthetic drugs to phytotherapy as an alternative treatment, there is still a gap in scientific evidences of plant-derived therapeutic benefits. One reason may be slow rate of translation of animal studies' findings into human clinical trials. Since metabolic disorders are multifactorial, it seems that poly-herbal medications, or drug-herbal combination are needed for their treatment. However, further researches to determine the most effective plant-derived metabolites, and their cellular mechanism in order to set priorities for well-designed animal and clinical trials, and also more studies with strong scientific evidences such as systematic review and meta-analysis of controlled studies are needed. PMID- 26157710 TI - Plasma oxysterol level in patients with coronary artery stenosis and its changes in response to the treatment with atorvastatin. AB - BACKGROUND: Considering the increasing incidence of coronary artery stenosis and its related complications, the importance of its etiology and inconsistent reports we aimed to determine the relationship between oxysterol, serum levels and severity of coronary atherosclerosis and effect of statins onoxysterol. METHODS: A total of 85 patients referred to Taleghani Hospital, Tehran, Iran during 2011-2012 withcoronary artery stenosis more than 75%, as determined by angiography, participated in the currentstudy. Their demographic information and history of smoking and taking atorvastatin was carefullyrecorded. Two milliliters of venous blood was obtained from each patient. The serum oxysterol levelof samples was measured using the enzyme-linked immunosorbent assay (ELISA) method. Statisticalanalysis was performed using SPSS v.19. RESULTS: Eighty five patients completed the study. Mean age of patients was 64.4 years; 51 (60%)were male; 55 (68%) had acute coronary syndrome and 30 (32%) had chronic stable angina.Mean+/ SD of plasma level of oxysterol was 24.8+/-0.2 pmol/ml. The normal range of oxysterol levelwas 13pmol/ml. Mean+/-SD of plasma oxysterol level in patients under statin therapy was 24.4+/-2.1pmol/ml. In patients without receiving statins, plasma oxysterol level was 26.38+/-1.6pmol/ml. CONCLUSION: Findings of the present study indicated significant correlation between serum oxysteroland severity of coronary artery stenosis. It also demonstrated that receiving atorvastatin is associatedwith significant reduction of plasma oxysterol level. PMID- 26157711 TI - Reduction in ischemic brain injury following the administration of pentoxifylline after transient global ischemia/ reperfusion in a rat model. AB - BACKGROUND: It is well known that the hippocampus, the CA1 Pyramidal cells in particular, is selectively vulnerable during global cerebral ischemia. Recently, it is observed that pentoxifylline has a neuroprotective effect. This study explored the pharmacological relationship between ischemiainduced cell death of the hippocampus and the efficacy of a vasodilator agent (pentoxifylline) in the prevention of delayed neuronal death. METHODS: This experimental study was performed on 4 groups: control, ischemia, experimental (200mg/kg pentoxifylline injection one hour prior to and one hour following ischemia) and vehicle (normal saline). Transient global ischemia was induced by bilateral common carotid arteries occlusion. To investigate the apoptotic bodies and caspase-3 activities as a central role in the execution phase of apoptosis, the brains were prepared for the TUNEL technique. RESULTS: Pentoxifylline administration limited apoptosis and caspase-3 activities in rats' hippocampi. Our data showed no significant difference between the number of apoptotic bodies in the CA1 region of the hippocampus in the control and pentoxifylline -treated groups (p= 0.994). The results of one- way ANOVA revealed that that ischemia significantly increased caspase-3 levels in the hippocampus (p< 0.05); however, the level of caspase-3 in pentoxifylline -treated rats was less than the ischemic group. CONCLUSION: These results suggest that the neuroprotective effect of pentoxifylline (200mg/kg) may be accompanied by a reduction in ischemic damage within the CA1 region of the hippocampus in rats subjected to transient global cerebral ischemia. PMID- 26157712 TI - Correlation between compliance regimens with health locus of control in patients with hypertension. AB - BACKGROUND: Epidemiological changes leading to chronic diseases are becoming more important day by day. Hypertension is also known as a chronic disease. Worldwide prevalence of hypertension have caused serious complications. The disease has become a health problem in all communities. This research aims at analyze the correlation between compliance with the treatment regimen and health locus of control in hypertension patients. METHODS: In this study, 130 patients diagnosed with high blood pressure have been included using convenience sampling. Information has been gathered including demographic data, compliance with the treatment regimen and health locus of control. The patient's blood pressure was measured twice and the mean was compared with the first blood pressure recorded in medical records. Data were analyzed using SPSS 17. RESULTS: The results showed that there is a direct correlation between the adherence to the treatment regimen with internal health locus of control. In patients with internal health locus of control, better compliance with treatment regimen was detected. CONCLUSION: Health locus of control is associated with treatment regimen. Considering health locus control can help nurses and managers in their health programs and also can motivate patients to participate in their self-care and improve patients care quality. PMID- 26157713 TI - Comparison of quadruple and triple Furazolidone containing regimens on eradication of helicobacter pylori. AB - BACKGROUND: The effectiveness of classic standard triple therapy regimen of helicobacter pylori (H. pylori) eradication has decreased to unacceptably low levels, largely related to development of resistance to metronidazole and clarithromycin. Thus successful eradication of H. pylori infections remains challenging. Therefore alternative treatments with superior effectiveness and safety should be designed and appropriately tested in all areas depending on the native resistance patterns. Furazolidone has been used successfully in eradication regimens previously and regimens containing furazolidone may be an ideal regimen. METHODS: H. pylori infected patients with proven gastric or duodenal ulcers and /or gastric or duodenal erosions at Imam Khomeini Hospital in Sari/Northern Iran, were randomly allocated into three groups: group A (OABF) with furazolidone (F) (200 mg bid.), group B (OABM-F) metronidazole (M) (500 mg bid.) for the first five days, followed by furazolidone (F) (200 mg bid.) for the second five days and group C (OAF) with furazolidone (F) (200 mg tid.). Omeprazole (O) (20 mg bid.) and amoxicillin (A) (1000 mg bid.) were given in all groups; bismuth (B) (240 mg bid.) was prescribed in groups A & B. Duration of all eradication regimens were ten days. Eight weeks after treatment, a 14C-urea breath test was performed for evaluation of H. pylori eradication. RESULTS: A total of 372 patients were enrolled in three groups randomly (124 patients in each group); 120 (97%) patients in group A (OABF), 120 (97%) in group B (OABM-F) and 116 (93%) in group C (OAF) completed the study. The intention-to-treat eradication rates were 83.7% (95% CI= 77.3-90.4), 79.8% (95% CI= 72.6-87), and 84.6% (95% CI= 78.2-91.1) and per-protocol eradication rates were 86.6% (95% CI= 80.5-92.8), 82.5% (95% CI= 75.6-89.4), and 90.5% (95% CI= 85.1-95.9) for groups OABF, OABM-F, and OAF, respectively. No statistical significant differences were found in case of severe drug adverse effects between the above mentioned three groups (p> 0.05). The most common side effects, namely nausea and fever, occurred in all groups, but more frequently in group C (OAF) (p< 0.05). CONCLUSION: In developing countries such as Iran, furazolidone-based regimens can substitute clarithromycinbased regimens for H. pylori eradication because of a very low level of resistance, low cost and high effectiveness. Considering per-protocol eradication rate of ten days OAF regimen, and the acceptable limit of ninety percent, we recommend this regimen in developing countries such as Iran to be substituted of classic standard triple therapy. In order to minimize rare serious adverse effects, one week high dose OAF regimen should be taken into consideration in other studies. PMID- 26157714 TI - Clinical outcomes and cost effectiveness of two aftercare models provided by general physicians and nurses to patients with severe mental illness. AB - BACKGROUND: Implementing community-based psychiatric services is one of the priorities of the WHO/EMRO mental health programs. This study presents an aftercare service, as a community based-service, for patients with severe mental illness (SMIs). METHODS: In this randomized controlled clinical trial design, 176 patients, who attended selective hospitals with SMI, were allocated into three groups: clinical case managers provided by general practitioners, nurses and the control group (usual treatment). The clients and their caregivers received monthly home visits (education and treatment supervision). The effectiveness of the intervention was measured by indicators of psychopathology such as scores of YOUNG, caregivers' knowledge and satisfaction with the services. Health-related quality of life (SF-36) was considered as the primary outcome variable. Data were collected at baseline and at 12 months follow-up. Direct and indirect medical costs were obtained through a periodic completion of questionnaires and interviews by caregivers. Cost effectiveness ratio was estimated as cost per QALY gained in each group. SPSS 16.0 was used in this survey and statistical methods were chi-square, ANOVA, Scheffe as post-Hoc test and paired sample t-test with 95% confidence interval and 0.05 significance level. RESULTS: The results of our study revealed that the score of YOUNG, caregivers' knowledge and satisfaction with service were improved in both intervention groups after 12 months. Improvement in health-related quality of life was observed in the general practitioner and nurse group. The incremental cost effectiveness ratio was 5740807 IRR and 5048459 IRR per QALYs gained in the general practitioner and nurse groups, respectively. CONCLUSION: The model of aftercare services provided by trained nurses is the most cost- effective and feasible model for Iran's socio economic conditions with low resource allocations. PMID- 26157715 TI - Relation between parvovirus B19 infection and fetal mortality and spontaneous abortion. AB - BACKGROUND: Infection with parvovirus B19 may cause fetal losses including spontaneous abortion, intrauterine fetal death and non-immune hydrops fetalis. The aim of this study is to determine the frequency of parvovirus B19 in formalin fixed placental tissues in lost fetuses using real-time PCR method. METHODS: In this cross-sectional study, 100 formalin fixed placental tissues with unknown cause of fetal death were determined using real-time PCR method after DNA extraction. RESULTS: Six out of 100 cases (6%) were positive for parvovirus B19 using real-time PCR. Gestational age of all positive cases was less than 20 weeks with a mean of 12.3 weeks. Three cases have a history of abortion and all of positive cases were collected in spring. Mean age of positive cases were 28 years. CONCLUSION: Parvovirus B19 during pregnancy can infect red precursor cells and induces apoptosis or lyses these cells that resulting in anemia and congestive heart failure leading to fetal death. Management of parvovirus B19 infection in pregnant women is important because immediate diagnosis and transfusion in hydropsic fetuses can decrease the risk of fetal death. PMID- 26157717 TI - Anti-hemorrhagic activity of Punica granatum L. flower (Persian Golnar) against heavy menstrual bleeding of endometrial origin: a double-blind, randomized controlled trial. AB - BACKGROUND: Heavy menstrual bleeding of endometrial origin (HMB) is a major healthcare problem in premenopausal women and affects several aspects of women's health and quality of life (QoL). The aim of this study was to compare the efficacy of Persian Golnar (PG) and tranexamic acid (TA) on heavy menstrual bleeding of endometrial origin (HMB) and patients' QoL. METHODS: A double-blind randomized controlled trial with parallel design and block randomization technique was conducted. A total of 94 women with HMB were randomly assigned to take either PG or TA for 5 days from day 1 of menses for three consecutive menstrual cycles. Blood loss was measured by the pictorial blood loss assessment chart (PBAC). Hematological assessments were made before the intervention and after treatment. QoL as a secondary outcome was evaluated using SF-36 and the menorrhagia questionnaire (MQ). Statistical analysis was performed using t-test, paired ttest, chi2 test, Mann-Whitney test, and Wilcoxon signed-rank test. RESULTS: In each group, 38 women (80.8%) completed the 3-month follow-up. Both PG and TA reduced blood loss. PBAC mean (SD) score was reduced from 304.92 (176.17) and 304.44 (192.72) to 164.60 (100.24) and 143.13 (96.07) after the third treatment cycle, respectively (p< 0.001). Furthermore, mean hemoglobin, Hb (SD) concentrations in the PG and TA groups increased significantly from 12.06 (0.86) and 11.53 (0.86)mg/dl to 13.02 (0.82) and 12.72 (0.88) mg/dl (p< 0.001). QoL was significantly improved in both groups (p< 0.001). However, there were no significant differences between the groups after the intervention. CONCLUSION: The results of the present study demonstrate the efficacy of PG in treating HMB in terms of clinical and QoL indicators. PMID- 26157716 TI - Comparison of health related quality of life between two groups of veteran and non-veteran spinal cord injured patients. AB - BACKGROUND: Patients with spinal cord injury (SCI) have a lower health related quality of life (HRQOL) compared to both healthy controls and the normal population. The aim of this study was to compare HRQOL between two groups of veteran and non-veteran SCI patients. METHODS: All male paraplegic non-veterans who had sustained complete SCI before 1988 and were residents of Tehran province (Iran), and a similar group of SCI veterans who consecutively participated in a health screening program were enrolled in this study. Patients fewer than 35 and older than 65 years of age were not included in this study. The participants were interviewed based on the Persian version of SF-36 questionnaire by two psychologists. Eight sub-scales and two physical and mental component summaries of the instrument were assessed. We used chi-square, odds ratio, Mann-Whitney U, independent t-test and linear regression for analysis. RESULTS: Overall, 25 veterans and 22 non-veterans were enrolled in the study. The mean age, time since injury and the presence of comorbid illnesses were not significantly different between the two groups (P>0.05). A greater number of veterans were married (p= 0.003) and employed (p= 0.047). On average, veterans had more years of formal education than non-veterans (p= 0.001). The mean (SD) bodily pain sub-scale was 72.73(31.253) for non-veterans and 49.7 (28.287) for veterans (p=0.011). Absence of comorbid illnesses was associated with a better physical component summary (p< 0.001). Employment was associated with a better mental component summary (p= 0.022). CONCLUSION: We did not find any differences in HRQOL between the two groups except for the bodily pain sub-scale. Further studies with larger sample sizes are recommended. PMID- 26157718 TI - A study of professional radiation hazards in CT scan and nuclear medicine workers using GTG-banding and solid stain. AB - BACKGROUND: CT scan and nuclear medicine exams deliver a great part of medical exposures. This study examined professional radiation hazards in CT scan and nuclear medicine workers. METHODS: In a cross sectional study 30 occupationally exposed workers and 7 controls (all from personnel of a laboratory) were selected. Physical dosimetry was performed for exposed workers. Blood samples were obtained from the experimental and control groups. Three culture mediums for each one were prepared in due to routine chromosome analysis using G-banding and solid stain. RESULTS: There were significant increased incidence of chromatid gap (ctg) and chromatid break (ctb) with mean+/-SD frequencies of 3+/-0.84 and 3.1+/ 1.40 per 100 cells respectively in the nuclear medicine workers versus controls with mean+/-SD frequencies of 1.9+/-0.69 and 1.3+/-0.84 for ctg and ctb, respectively. Chromosome gaps (chrg) were higher significantly in the nuclear medicine population (2.47+/-0.91) than in controls (1.4+/-0.9) (p< 0.05). In CT scan group the ctg and ctb were increased with a mean+/-SD frequency of 2.7+/ 0.79 and 2.6+/-0.91 per 100 cells respectively compared with control group. The mean+/-SD frequencies of the chrb were 2.0+/-0.75 and 0.86+/-0.690 per 100 cells for exposed workers and control group, respectively. CONCLUSION: This study showed chromosome aberrations in peripheral lymphocytes using solid stain method are reasonable biomarker reflecting personnel radiation damage. PMID- 26157719 TI - Diagnostic accuracy of sonohysterography compared to endometrial biopsy in pre menopausal women with abnormal uterine bleeding. AB - BACKGROUND: AUB is a common cause of women's referring to gynecologists. Although hysteroscopy is known as the gold standard technique for diagnosing the cause of AUB, sonohysterography is less invasive, and it is performed by general gynecologists. The purpose of this study was to evaluate the diagnostic performance of sonohysterography compared to the results of the endometrial biopsy, guided by hysteroscopy in premenopausal women with AUB. METHODS: This cross- sectional Study was conducted at the gynecological clinic of Roointan Arash women's Hospital from February 2011 to February 2012. The study participants were 90 premenopausal female patients, who visited the clinic for AUB, for whom, hormonal, iatrogenic and systemic causes were ruled out. They underwent sonohysterography and hysteroscopy and endometrial biopsy. The results of sonohysterography and pathological reports of endometrial biopsy were compared, and the diagnostic accuracy of sonohysterography for normal endometrium, endometrial polyps, sub mucosal fibroids and endometrial hyperplasia was evaluated. RESULTS: The diagnostic accuracy of sonohysterography was found to be 89.1% for the normal endometrium, 90% for endometrial polyps, 99% for sub mucosal fibroids and 94.4% for endometrial hyperplasia. CONCLUSION: Sonohysterography is an accurate, non-invasive and cost-effective method for diagnosing AUB causes compared to hysteroscopy and endometrial biopsy. Therefore, as an initial diagnostic step, it can replace the alternative and less accurate methods such as transvaginal ultrasound, blind endometrial curettage or more costly and invasive methods such as hysteroscopy requiring anesthesia. PMID- 26157720 TI - Effect of coenzyme Q10 supplementation on exercise-induced response of inflammatory indicators and blood lactate in male runners. AB - BACKGROUND: Heavy exercise cause muscle damage associated with production of inflammatory agents. The purpose of present study was to determine the effect of acute and 14-day Coenzyme Q10 supplementation on inflammatory, blood lactate and muscle damage in male middle-distance runners. METHODS: Eighteen male middle distance runners in a randomized and quasi experimental study were allocated into two equal groups: supplement group (n=9, Coenzyme Q10: 5mg/kg/day) and placebo group (n= 9, Dextrose: 5mg/kg/day). After acute (1day) and 14-day supplementation, all subjects were participated in a training like running (competitive 3000 meters). Blood samples were obtained in the four phases: one hour before and 18-24 hours after two running protocols. Lactate, serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP) and creatine kinase (CK) were analyzed. Repeated ANOVA and Bonferuni as a post hoc tests were used to determine the changes in four stages. Differences between groups were determined by t-test. RESULTS: The results showed that acute and short-term Coenzyme Q10 supplementation had not significant effect on basal parameters. The acute coenzyme Q10 supplementation attenuated only the exercise induced increase in response of the plasma CRP. The short-term (14-day) coenzyme Q10 supplementation attenuated the exercise-induced increase in response of the lactate, serum interleukin- 6, tumor necrosis factor-alpha, and CRP in male middle-distance runners. However, the acute and short-term coenzyme Q10 supplementation had not any significant effect on the exerciseinduced increase response of total serum creatine kinase. CONCLUSION: Based on the present results, it can be concluded that the 14-day coenzyme Q10 supplementation (5mg.kg 1.day-1) is more effective than the acute supplementation to overcome the exercise-induced adverse responses in some oxidative, inflammatory and biochemical parameters. Therefore, short-term coenzyme Q10 supplementation is recommended to reduce exercise-induced adverse consequences. PMID- 26157721 TI - Comparison of c-Kit expression between primary and metastatic melanoma of skin and mucosa. AB - BACKGROUND: Melanoma causes the greatest morbidity and mortality of all skin cancers. Mucosal melanoma is a rare but highly aggressive neoplasm. According to previous studies the prevalence of KIT mutations in acral lentiginous and mucosal melanomas is relatively low (less than 15-20%), but it can have profound therapeutic implications for localized high risk or metastatic diseases. Our goal was to evaluate c-Kit expression in different types of primary and metastatic melanoma to discriminate potential candidates for targeted therapy. METHODS: We designed a cross-sectional study and selected 50 cases of malignant melanoma (primary, metastatic cutaneous, and mucosal) from the affiliated hospitals of Shiraz University of Medical Sciences in the period of 2008 to 2012. Immunohistochemistry for KIT expression was performed. Multistage sampling method was selected for sampling and chi-square test was used for statistical analysis. RESULTS: In our study, male to female ratio was 1.77. The male sex was correlated with higher tumor stage (p< 0.05). 62% (n= 31) of cases showed at least 5% of KIT positive cells, consist of 18% (n= 9) with 5-50%, 16% (n= 8) with 51-95%, and 28% (n= 14) of cases showed more than 95% of cells expressing KIT. But in 38% (n= 19) of cases KIT expression was less than 5% of positive cells. Tumor stage was positively correlated with tumor cell immunoreactivity and intensity (p< 0.05). Metastatic melanoma showed lower percentage (43%) of positivity. Intensity of staining and percentage of positive cells were positively correlated (p< 0.001). CONCLUSION: In primary melanomas, significant KIT expression was found by immunohistochemistry, which may be useful to screen the patients for advising to KIT mutation analysis and targeted therapy. PMID- 26157722 TI - Determinants of responsibility for health, spiritual health and interpersonal relationship based on theory of planned behavior in high school girl students. AB - BACKGROUND: Adolescence is a sensitive period of acquiring normal and abnormal habits for all oflife. The study investigates determinants of responsibility for health, spiritual health and interpersonal relations and predictive factors based on the theory of planned behavior in high school girl students in Tabriz. METHODS: In this Cross-sectional study, 340 students were selected thorough multi stage sampling. An author-made questionnaire based on standard questionnaires of Health Promotion and Lifestyle II (HPLPII), spiritual health standards (Palutzian & Ellison) and components of the theory of planned behavior (attitudes, subjective norms, perceived behavioral control, and behavioral intention) was used for data collection. The questionnaire was validated in a pilot study. Data were analyzed using SPSS v.15 and descriptive and analytical tests (Chi-square test, Pearson correlation co-efficient and liner regression test in backward method). RESULTS: Students' responsibility for health, spiritual health, interpersonal relationships, and concepts of theory of planned behavior was moderate. We found a significant positive correlation (p<0/001) among all concepts of theory of planned behavior. Attitude and perceived behavioral control predicted 35% of intention of behavioral change (p<0.001). Attitude, subjective norms, and perceived behavioral control predicted 74% of behavioral change in accountability for health (p<0.0001), 56% for behavioral change in spiritual health (p<0.0001) and 63% for behavioral change in interpersonal relationship (p<0.0001). CONCLUSION: Status of responsibility for health, spiritual health and interpersonal relationships of students was moderate. Hence, behavioral intention and its determinants such as perceived behavioral control should be noted in promoting intervention programs. PMID- 26157723 TI - The effect of exercise therapy on cognitive functions in multiple sclerosis patients: A pilot study. AB - BACKGROUND: The positive impacts of exercise therapy on patients' cognitive problems still remain unknown. This study was a pilot intervention to examine the effects of combined exercise on the cognitive problems of patients with multiple sclerosis (MS) in Iranian MS Society over 2012 to 2013. METHODS: This quasi experimental research was carried out in the form of a pretest/posttest study. Forty two patients with MS were selected from those visiting the rehabilitation center of Iranian MS Society, using non-probability convenience sampling. The Expanded Disability Status Scale (EDSS) of each patient was recorded before the intervention and Brief Repeatable Battery of Neuropsychological (BRB-N) test was administered before and after the intervention. The data were analyzed using the analytical tests such as Wilcoxon test. RESULTS: Of 21 participants, 17 subjects (82%, n=14) female with mean (+/-SD) age of 37 (+/-9.98) years and mean (+/-SD) EDSS of 2.35 (+/-0.90) completed all stages of the study. Changes in long-term storage and permanent long-term retrieval of information after the intervention were statistically significant (p<0.001). In addition, the change in the average of total delay after the intervention was also significant by 1.11 (p<0.001). CONCLUSION: Our study confirmed the possibility of change in the cognitive abilities of MS patients through physical interventions. This finding emphasizes the necessity of more clinical examinations and increases the hopes for new rehabilitation methods for the disorder. PMID- 26157724 TI - A 5-year scientometric analysis of research centers affiliated to Tehran University of Medical Sciences. AB - BACKGROUND: Since Tehran University of Medical Sciences (TUMS) has the oldest and highest number of research centers among all Iranian medical universities, this study was conducted to evaluate scientific output of research centers affiliated to Tehran University of Medical Sciences (TUMS) using scientometric indices and the affecting factors. Moreover, a number of scientometric indicators were introduced. METHODS: This cross-sectional study was performed to evaluate a 5 year scientific performance of research centers of TUMS. Data were collected through questionnaires, annual evaluation reports of the Ministry of Health, and also from Scopus database. We used appropriate measures of central tendency and variation for descriptive analyses. Moreover, uni-and multi-variable linear regression were used to evaluate the effect of independent factors on the scientific output of the centers. RESULTS: The medians of the numbers of papers and books during a 5-year period were 150.5 and 2.5 respectively. The median of the "articles per researcher" was 19.1. Based on multiple linear regression, younger age centers (p=0.001), having a separate budget line (p=0.016), and number of research personnel (p<0.001) had a direct significant correlation with the number of articles while real properties had a reverse significant correlation with it (p=0.004). CONCLUSION: The results can help policy makers and research managers to allocate sufficient resources to improve current situation of the centers. Newly adopted and effective scientometric indices are is suggested to be used to evaluate scientific outputs and functions of these centers. PMID- 26157725 TI - Serum levels of vitamins A and D, and zinc in children with acute diarrhea: A cross-sectional study. AB - BACKGROUND: Diarrhea is a leading cause of mortality and morbidity during the early life period especially in developing countries. Micronutrients deficiencies have been proposed either as a risk factor or a consequence of diarrhea. Association studies highlight the relation of vitamins and minerals' deficiencies with acute diarrhea. In this regard we aimed to evaluate the status of vitamins A and D, and zinc serum levels in children with acute diarrhea. METHODS: In this cross sectional study performed in a referral teaching hospital, we measured and compared baseline vitamin A, 25-hydroxy vitamin D (25(OH)D), and zinc serum levels in 25 children admitted with acute diarrhea and 25 other children who were admitted for undergoing elective surgeries. RESULTS: 25-(OH)D levels were significantly lower in the diarrhea group (p=0.03). We were unable to demonstrate a significant difference in the levels of vitamin A and zinc between the case and control groups (p= 0.14 and p=0.07, respectively). CONCLUSION: We observed lower serum 25(OH)D levels in children with acute diarrhea. Whether this finding indicates a premorbid risk factor or simply a consequence of diarrhea needs further studies. Regardless of the cause and effect relationship, supplementation with vitamin D in acute diarrhea remains as a plausible consideration. PMID- 26157726 TI - Integration of suicide prevention program into primary health care network: a field clinical trial in Iran. AB - BACKGROUND: Suicide prevention is one of the priorities in policies of Iranian Ministry of Health and Medical Education (MHME). The suicide prevention program had two main parts of identifying and treatment of the depressed and suicide high risk individuals by Primary Health Care (PHC) network. The main aim of this study was to evaluate the results of integration of the program into PHC network in two cities with moderate to high rate of suicide with diverse socio-cultural backgrounds. METHODS: This work as a field trial study was conducted in Nahavand and Savojbolagh from April 2010 to March 2011 (12 months). A screening tool was designed. Required capacities such as treatment, referral and registration system were provided six months before the main study. The intervention phase (for one year) including the treatment process and five consultation sessions was conducted to identify depressed people and individuals with high risk of suicide. The data were analyzed by Chi square test. RESULTS: After one year of intervention, the rate of committing suicide became 4.98 and 3.36 per one hundred thousand population in Nahavand and Savojbolagh, respectively (16 and 1.6 per 100,000 in the year of before intervention respectively, 2009-2010). The female: male ratio of committing suicide was 2:1 in Nahavand and 1:1 in Savojbolagh. The most common method of committing suicide was drug intoxication in both cities. The identified cases by health workers at rural setting were 33 to 44 per 1000, in which 1.3 cases per 1000 population had been approved by general physicians. CONCLUSION: This study approved the feasibility and efficacy of integration of suicide prevention program into PHC. The increased rate of suicide in Savojbolagh could be related to low rate of screening and lack of treatment facilities (hospitalization and electroconvulsive therapy (ECT), and part-time psychiatrist. Increasing the PHC capacities could improve the health network efficiency to identify and manage depressed and at risk of suicide individuals. Screening tool/s and method have to be improved to provide better results. PMID- 26157727 TI - Prevalence of gestational diabetes mellitus in Rafsanjan: a comparison of different criteria. AB - BACKGROUND: Gestational diabetes mellitus (GDM) is common during pregnancy. This survey was designed based on the frequency of GDM among an urban population according to the American Diabetes Association (ADA) and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. METHODS: We included all pregnant women who were admitted to a gynecology clinic from September 2012 until May 2013. The fasting blood sugar (FBS) was measured. Those having FBS>= 126 mg/dl were excluded from the study. All women underwent a standard OGTT (oral glucose tolerance test) by ingesting 75g of glucose in the 24th to 32nd week of their pregnancy. RESULTS: Two hundred ninety pregnant women with a mean+/-SD age of 27.72+/-5.091 years were included in the study. The mean+/-SD FBS, blood glucose one hour and two hours after ingesting 75g of glucose were 82.48+/-9.41, 146.86+/-34.22 and 114.21+/-27.79 mg/ dl, respectively. Based on the criteria of the ADA, 9.3% (n= 27) of the admitted patients suffered from GDM. For the IADPSG and the WHO, those numbers were 31% (n= 90) and 15.2% (n= 44), respectively. CONCLUSION: The prevalence of GDM was 1.5-times and 3 times higher when the IADPSG based data were compared to those of the WHO or the ADA. PMID- 26157728 TI - A youth-led reproductive health program in a university setting. AB - BACKGROUND: Reproductive health problems affect youths in all countries. There is an urgent need to enhance youths reproductive health services to provide a healthy life for this group. In this regard, the present study aimed to evaluate the Reproductive Health Peer Education Program based on the opinion of university students. METHODS: This interventional study was conducted in Qazvin University of Medical Sciences through the peer education method. The participants of this study were 24 peer educators who received training in a 40 hour peer educator training course. The peer education program was implemented in the university. In order to evaluate this community- based intervention, 329 students were selected through the stratified sampling method and their opinion was assessed. Descriptive statistical methods were used by SPSS software for data analysis. RESULTS: The results of the study revealed that peer education was accepted by 64.7% (n= 213) of the students, according to their opinion. The educational priorities of the students were as follows: pre-marriage counseling (78%, n= 166); STI/AIDS (17%, n= 36); and contraception (5%, n= 11). The peer education program was recognized as the most required reproductive health service in the university by 55.3% (n= 118) of the students. They believed that the most important duties of the peer educators were: education (33.5%, n= 71); counseling (30.4%, n= 65); referring to a counseling center (21.6%, n= 46) and referring to a therapeutic center (14.5%, n= 31). Also, the students stated that confidentiality (53%, n= 113), suitable communication (26%, n= 55) and sufficient knowledge (21%, n= 45) were desired characteristics for the peer educators. CONCLUSION: According to the students' opinion, peer education could provide suitable reproductive health services and could also be beneficial for reproductive health promotion and might reinforce positive behaviors in youths. Reproductive health peer- counseling is a sensitive process, and it is best to be conducted under the supervision of specialists. PMID- 26157729 TI - Improvement of Accuracy in Environmental Dosimetry by TLD Cards Using Three dimensional Calibration Method. AB - INTRODUCTION: The angular dependency of response for TLD cards may cause deviation from its true value on the results of environmental dosimetry, since TLDs may be exposed to radiation at different angles of incidence from the surrounding area. OBJECTIVE: A 3D setting of TLD cards has been calibrated isotropically in a standard radiation field to evaluate the improvement of the accuracy of measurement for environmental dosimetry. METHOD: Three personal TLD cards were rectangularly placed in a cylindrical holder, and calibrated using 1D and 3D calibration methods. Then, the dosimeter has been used simultaneously with a reference instrument in a real radiation field measuring the accumulated dose within a time interval. RESULT: The results show that the accuracy of measurement has been improved by 6.5% using 3D calibration factor in comparison with that of normal 1D calibration method. CONCLUSION: This system can be utilized in large scale environmental monitoring with a higher accuracy. PMID- 26157730 TI - A New Approach for Heterogeneity Corrections for Cs-137 Brachytherapy Sources. AB - BACKGROUND: Most of the current brachytherapy treatment planning systems (TPS) use the TG-43U1 recommendations for dosimetry in water phantom, not considering the heterogeneity effects. OBJECTIVE: The purpose of this study is developing a method for obtaining correction factors for heterogeneity for Cs-137 brachytherapy sources based on pre-calculated MC simulations and interpolation. METHOD: To simulate the effect of phantom heterogeneity on dose distribution around Cs-137 sources, spherical water phantoms were simulated in which there were spherical shells of bone with different thicknesses (0.2cm to 1.8cm with 0.1cm increment) at different distances (from 0.1cm to 10cm, with 0.5cm increment) from the source center. The spherical shells with 0.1cm thickness at different distances from 0.1cm to 10cm were used as tally cells. The doses at these cells were obtained by tally types F6, *F8, and *F4.The results indicate that the percentage differences between the doses in heterogeneity sections with the dose at the same positions inside the homogeneous water phantom vary when the distance of bone section from the source center increases, because of decreasing the average energy of photons reaching the bone layer. Finally, the results of Monte Carlo simulations were used as the input data of MATLAB software, and the percentage dose difference for each new configuration (i.e. different thickness of inhomogenity at different distances from the source) was estimated using the 2D interpolation of MATLAB. RESULTS: According to the results, the algorithm used in this study, is capable of dose estimation with high accuracy. CONCLUSION: The developed method using the results of Monte Carlo simulations and the dose interpolation can be used in treatment planning systems for heterogeneity corrections. PMID- 26157731 TI - A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins. AB - INTRODUCTION: Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects. MATERIALS AND METHODS: Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure. RESULTS: Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042). CONCLUSION: Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life threatening situations such as exposure to lethal doses of ionizing radiation. The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C. PMID- 26157732 TI - Assessment of the Radiation Attenuation Properties of Several Lead Free Composites by Monte Carlo Simulation. AB - BACKGROUND: In diagnostic radiology lead apron, are usually used to protect patients and radiology staff against ionizing radiation. Lead apron is a desirable shield due to high absorption and effective attenuation of x-ray photons in the diagnostic radiology range. OBJECTIVE: Although lead aprons have good radiation protection properties, in recent years, researchers have been looking for alternative materials to be used instead of lead apron because of some problems derived from lead-content of aprons. Because of its lead-content, these radiation protection garments are so heavy and uncomfortable for the staff to wear, particularly in long-time uses. In addition, lead is a toxic element and its disposal is associated with environmental and human-health hazards. METHOD: In this study, several new combinations of lead free materials ((W-Si), (W-Sn-Ba EPVC ), (W-Sn-Cd-EPVC)) have been investigated in the energy range of diagnostic radiology in two geometries: narrow and broad beam. Geometries of the radiation attenuation characteristics of these materials was assessed in 40, 60, 90 and 120 kVp and the results compared with those of some lead-containing materials ((Pb Si), (Pb-EPVC)). RESULTS: Lead shields still provide better protection in low energies (below 40 kVp). Combination of W-Sn-Cd-EPVC has shown the best radiation attenuation features in 60 and 90 kVp and the composition of (W-Sn-Ba-EPVC) represents the best attenuation in 120 kVp, even better than previously mentioned lead- containing composites. CONCLUSION: Lead free shields are completely effective for protection against X-ray energies in the range of 60 to 120 kVp. PMID- 26157733 TI - Comparison between Clinically Used Irregular Fields Shielded by Cerrobend and Standard Lead Blocks. AB - INTRODUCTION: In radiation therapy centers across Iran, protection of normal tissues is usually accomplished by either Cerrobend or lead block shielding. In this study, the influence of these two shielding methods on central axis dose distribution of photon beam a Cobalt unit was investigated in clinical conditions. MATERIALS AND METHODS: All measurements were performed for 60Co gamma ray beams and the Cerrobend blocks were fabricated by commercial Cerrobend materials. Standard lead block shields belonged to Cobalt unit. Data was collected through a calibrated ionization chamber, relative dosimetry systems and a TLD dosimetery. RESULTS: Results of the percent depth dose (PDD) measurements at depths of 0.5, 1, 5, 10, 15 and 20 cm for 23 different field sizes of patients with head and neck cancer showed no significant differences between lead and Cerrobend shielding methods. Measurement results of absolute dosimetry in depths of 1.5, 3, 5, 7, 10 and 12 cm also showed no significant differences between these two shielding methods. The same results were obtained by TLD dosimetry on patient skin. CONCLUSION: Use of melt shielding methods is a very easy and fast shield-making technique with no differences in PDD, absolute and skin dose between lead and Cerrobend block shielding methods. PMID- 26157734 TI - Corrigendum to: "Removing ECG Artifact from the Surface EMG Signal Using Adaptive Subtraction Technique" published in J Biomed Phys Eng 2014; 4(1):31-38. PMID- 26157735 TI - The assessment of cardiac function in veno-venous extracorporeal membrane oxygenation: the emerging role of bedside echocardiography. PMID- 26157736 TI - Major themes for 2014 in cardiothoracic and vascular anaesthesia and intensive care. AB - There has been significant progress throughout 2014 in cardiothoracic and vascular anaesthesia and intensive care. There has been a revolution in the clinical approach to acute and chronic adult aortic diseases. Contemporary management of adult aortic disease is based on etiology, clinical presentation, extent, and integrated intervention with medical, endovascular and/or surgical measures. Further European guidelines have explored in depth the cardiovascular management in non-cardiac surgery with a thematic focus to reduce perioperative mortality from the leading offender, namely myocardial ischemia. Integrated guidelines address the management of myocardial revascularization including the percutaneous and surgical options. Despite 50 years since the first coronary artery bypass grafting procedure and impressive advances in interventional cardiology, surgical revascularization remains a gold standard for many patients with coronary artery disease. These advances in 2014 will likely further improve perioperative outcomes for our patients. PMID- 26157737 TI - Myocardial recovery during mechanical circulatory support: cellular, molecular, genomic and organ levels. AB - Mechanical circulatory support is a life-saving therapy that will become either a bridge-to-transplantation or definitive therapy if heart transplantation is not possible. Failing hearts supported by a ventricular assist device were often found to recover at molecular and cellular level but translation of these changes into functionally-stable cardiac recovery allowing long-term heart transplantation/ventricular assist device-free outcomes after weaning from ventricular assist device is relatively rare and related to the etiology, severity and duration of myocardial damage. The reason for the discrepancy between high recovery rates on the cellular and molecular levels and the low rate of cardiac recovery allowing ventricular assist device explantation is unknown. PMID- 26157738 TI - Paracetamol: a review with specific focus on the haemodynamic effects of intravenous administration. AB - Paracetamol is one of the most commonly used drugs worldwide with non prescription sales exceeding 25 thousand million doses per year in the United States of America. The haemodynamic effects of the intravenous paracetamol formulations are largely understudied. There is an emerging body of evidence suggesting that intravenous paracetamol may cause iatrogenic hypotension. Little is known as to the mechanisms of this phenomenon or if intravenous paracetamol indeed does cause hypotension. As paracetamol has negligible solubility in aqueous solutions, many of the commercially available intravenous formulations contain mannitol (up to 3.91 g/100 mL paracetamol) as a stabilising ingredient. It is unknown if mannitol is a contributing factor in the observed hypotension. In this review, we outline the development of paracetamol's current intravenous formulations, describe the composition of these formulations, and overview the literature pertaining to the proposed phenomenon of paracetamol-induced altered hypotension. Understanding the pharmacokinetic and pharmacodymanic properties of intravenous paracetamol may have important clinical implications for vulnerable patients in subgroups where haemodynamic stability is at risk such as those undergoing elective and emergency surgery. PMID- 26157739 TI - The attractiveness of network meta-analysis: a comprehensive systematic and narrative review. AB - Network meta-analysis provides a global estimate of comparative treatment effectiveness combining both direct and indirect evidence. In the past decade, the medical literature has witnessed a rapid increase in the possibility to combine evidence from different treatment comparisons. This opportunity is attractive for clinicians since their major concern is to identify the single best available treatment. In addition, despite the sudden increase of publications concerning network meta-analysis, only a limited number focus on methodological and statistical aspects, and many issues remain unclear. The aim of our work was to explore and emphasize the potential attractiveness of network meta-analyses. We performed a systematic and narrative review (last updated on April 15, 2014) in order to assess the scholarly diffusion of network meta analyses. The following data were collected: author identification, year and journal of publication, PubMed index, number of treatments and studies included, characteristics of network configuration, nature of primary outcome, clinical indication, type of intervention investigated and medical area. Since 2003 there has been an exponential increase in the number of published network meta analyses. Out of 340 articles included according to our selection criteria, encompassing 248 treatment networks, cardiovascular and pulmonary diseases were the most prevalent topics, with an average of 5 treatments being compared stemming from an average of 10 controlled trials. In conclusion, network meta analyses are becoming increasingly attractive as they offer a comprehensive framework for decision-making. Whether they will also contribute to improvements in patient outlook remains to be proven. PMID- 26157740 TI - Use of levosimendan in patients with heart failure in different settings: case reports and treatment guidance. AB - INTRODUCTION: The inodilator levosimendan was developed as a treatment for acutely decompensated severe chronic heart failure. In recent years, its use has broadened to treatment of heart failure in different settings. These include advanced chronic heart failure, and other scenarios where haemodynamic stability is sought, such as pre-operative treatment of patients at risk of low cardiac output syndrome or peri-operative heart failure. The aims of this presentation of four case reports were to compare the use of levosimendan in different settings, and to highlight differences and similarities in the effects obtained, with the purpose of defining common guidance on the use of levosimendan. METHODS: We retrospectively reviewed the records of patients with heart failure in the registries of our wards, identified and described four cases where levosimendan was received in four different settings. We provide here a systematic report on these four cases. RESULTS: One patient suffered from acutely worsened chronic heart failure, one from advanced chronic heart failure, with repetitive treatment needed, one experienced acute ventricular failure as a result of a perioperative myocardial infarction, and one with left-ventricular function impairment and planned surgery. CONCLUSIONS: Heart failure arising from different aetiologies and occurring in different settings is amenable to successful treatment with levosimendan. PMID- 26157741 TI - Tricuspid annular plane systolic excursion (TAPSE) predicts poor outcome in patients undergoing acute pulmonary embolectomy. AB - INTRODUCTION: Right ventricular failure remains a major cause of mortality during acute pulmonary embolism. Right ventricular function can be assessed with transesophageal echocardiography. However, due to the complex right ventricular anatomy, only a few echocardiographic parameters are reliable and easily obtainable intraoperatively. Tricuspid annular plane systolic excursion is a validated parameter of global right ventricular function. METHODS: Data from 81 patients with acute pulmonary embolus undergoing pulmonary embolectomy were evaluated. Transesophageal echocardiography derived parameters of right ventricular function were obtained and compared to tricuspid annular plane systolic excursion measurements. Patients were then divided into two groups (TAPSE < 18 mm and >=18 mm). RESULTS: The patient population consisted of 46 males and 35 females, mean age 61.0 +/- 12.9 years. Patients in the TAPSE <18 mm group had significantly larger diastolic (p=0.0015) and systolic (p=0.0031) right ventricular diameters, lower right ventricular fractional area change (p=0.0065) and greater degrees of tricuspid regurgitation (p=0.0001) compared to patients with TAPSE >=18 mm. In addition, all patients who needed intraoperative cardiopulmonary resuscitation (11/81) or died intraoperatively (8/81) belonged to the TAPSE <18 mm group. Logistic regression analysis confirmed TAPSE <18 mm as an independent risk factor for intraoperative cardiopulmonary resuscitation and death. CONCLUSIONS: Transesophageal echocardiography derived TAPSE is easily obtainable and correlates well with other standardized parameters of right ventricular function. TAPSE <18 mm is an independent predictor of intraoperative cardiopulmonary resuscitation and death in patients undergoing emergent pulmonary embolectomy. PMID- 26157742 TI - Extracorporeal membrane oxygenation for Life-threatening ANCA-positive pulmonary capillaritis. A review of UK experience. AB - INTRODUCTION: Anti-neutrophil cytoplasmic antibody positive pulmonary capillaritis complicated by diffuse alveolar hemorrhage is a potentially fatal condition for which extracorporeal membrane oxygenation can facilitate improved outcomes and potential cure. Diffuse alveolar hemorrhage can be the initial presentation of an autoimmune disorder. The management is centered on the use of immunosuppressive therapy, which requires time, with fatality often occurring for these patients. We showed two very young patients with no previous history of vasculitis presenting with life threatening pulmonary hemorrhage due to anti neutrophil cytoplasmic antibody positive vasculitis, whose management was facilitated with extracorporeal membrane oxygenation. METHODS: We reviewed the clinical presentation and course of the first two patients with diffuse alveolar hemorrhage for anti-neutrophil cytoplasmic antibody positive vasculitis managed with veno-venous extracorporeal membrane oxygenation. We highlighted and analysed the unique challenges encountered in managing these patients. RESULTS: The two patients were referred for extracorporeal membrane oxygenation since conventional ventilation was inadequate to provide physiologic support for respiratory failure. Clinical improvement was achieved without exacerbation of the pulmonary hemorrhage despite the use of anticoagulants. This provided time for the immunosuppressants to take effect. Both patients were discharged and were cured of the underlying condition. CONCLUSIONS: Extracorporeal membrane oxygenation has a role in the management of patients with severe respiratory failure due to anti neutrophil cytoplasmic antibody positive capillaritis. Early recognition and referral for extracorporeal membrane oxygenation are vital to achieve a favourable outcome. PMID- 26157744 TI - Novel airway management in a child with Goldenhar Syndrome at a remote location. PMID- 26157743 TI - Ultrasound-guided carotid sheath block for carotid endarterectomy: a case series of the spread of injectate. AB - INTRODUCTION: We aimed to show the spread of local anesthetic following an ultrasound-guided, double-injection technique of a carotid sheath block before carotid endarterectomy. METHODS: The study included 15 patients scheduled for elective carotid endarterectomy. The carotid sheath block was performed after ultrasound-guided localization of the carotid bifurcation (level C4-C6) at the posterior border of the sternocleidomastoid muscle. A mix of 7.5 mL ropivacaine 0.75%, 7.5 mL prilocaine1% and 3 mL iopromidum was injected at the base of the carotid bifurcation. An additional 15 mL of the mixture was administered subcutaneously at the surgical incision line. Thirty minutes after the block, a computed tomography scan of the head, neck region and upper thorax was performed to reconstruct a 3-D distribution of the injectate. RESULTS: All patients achieved C2-C4 dermatomal sensory blockade. None required conversion to general anesthesia. The injectate spread ranged from the vertebral body of C1 to the vertebral body of T3. The mean volume of distribution was 97+/-13 mL, the craniocaudal spread 138+/-19 mm, dorsoventral 57+/-8 mm and coronal 53+/-8 mm. The mean carotid artery circumference contact was 252 degrees +/-77, with four patients (27%) presenting with a ring formation (360 degrees ) around the carotid artery. CONCLUSIONS: Ultrasound-guided carotid sheath block provided an extensive spread of local anesthetic. A complete ring formation of local anesthetic around the artery does not seem necessary for a successful anesthesia. The resulting nerve blockade thus appears sufficient for surgery, with minor risks compared to blind methods. PMID- 26157745 TI - Timing of tracheostomy and associated complications in cardiothoracic intensive care patients. PMID- 26157746 TI - Hepatitis C virus-induced hepatocellular carcinoma. AB - Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs. PMID- 26157747 TI - New perspectives on the management of hepatocellular carcinoma with portal vein thrombosis. AB - Despite advances in the treatment of hepatocellular carcinoma (HCC), managing HCC with portal vein thrombosis (PVT) remains challenging. PVT is present in 10-40% of HCC cases at the time of diagnosis and its therapeutic options are very limited. Current guidelines mainly recommend sorafenib for advanced HCC with PVT, but surgery, transarterial chemoemolization, external radiation therapy, radioembolization, transarterial infusion chemotherapy, and combination therapy are also still used. Furthermore, several new emerging therapies such as the administration of immunotherapeutic agents and oncolytic viruses are under investigation. This comprehensive literature review presents current and future management options with their relative advantages and disadvantages and summary data on overall survival. PMID- 26157748 TI - Hepatitis C virus infection in patients with hemophilia in Korea: Is antiviral therapy effective and safe? PMID- 26157749 TI - Highly effective peginterferon alpha-2a plus ribavirin combination therapy for chronic hepatitis C in hemophilia in Korea. AB - BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon alpha-2a plus ribavirin for CHC in hemophilia. METHODS: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests. RESULTS: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naive patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis. CONCLUSIONS: Peginterferon alpha-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events. PMID- 26157751 TI - Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis. AB - BACKGROUND/AIMS: Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs. METHODS: We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (alpha SMA). The levels of growth factors and cytokines were evaluated by an indirect co culture system of activated HSCs with BM-MSCs. RESULTS: The BM-MSCs in the direct co-culture system significantly decreased the production of alpha-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-beta1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of alpha-SMA and inducing the apoptosis of HSCs. CONCLUSIONS: These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs. PMID- 26157750 TI - Impact of prior lamivudine use on the antiviral efficacy and development of resistance to entecavir in chronic hepatitis B patients. AB - BACKGROUND/AIMS: To determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naive chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance. METHODS: We retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naive patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance. RESULTS: Genotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naive group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance. CONCLUSIONS: ETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance. PMID- 26157752 TI - Retrospective analysis of autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in Korea: characteristics, treatments, and outcomes. AB - BACKGROUND/AIMS: Overlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone. METHODS: This retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes. RESULTS: The AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups. CONCLUSIONS: The AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients. PMID- 26157753 TI - Predictive factors of contrast-enhanced ultrasonography for the response to transarterial chemoembolization in hepatocellular carcinoma. AB - BACKGROUND/AIMS: The predictive role of contrast-enhanced ultrasonography (CEUS) before performing transarterial chemoembolization (TACE) has not been determined. We assessed the possible predictive factors of CEUS for the response to TACE. METHODS: Seventeen patients with 18 hepatocellular carcinoma (HCC) underwent TACE. All of the tumors were studied with CEUS before TACE using a second generation ultrasound contrast agent (SonoVue(r), Bracco, Milan, Italy). The tumor response to TACE was classified with a score between 1 and 4 according to the remaining enhancing-tumor percentage based on modified response evaluation criteria in solid tumors (mRECIST): 1, enhancing tumor <25%; 2, 25%<=enhancing tumor<50%; 3, 50%<=enhancing tumor<75%; and 4, enhancing tumor>=75%). A score of 1 was defined as a "good response" to TACE. The predictive factors for the response to TACE were evaluated during CEUS based on the maximum tumor diameter, initial arterial enhancing time, arterial enhancing duration, intensity of arterial enhancement, presence of a hypoenhanced pattern, and the feeding artery to the tumor. RESULTS: The median tumor size was 3.1 cm. The distribution of tumor response scores after TACE in all tumors was as follows: 1, n=11; 2, n=4; 3, n=2; and 4, n=1. Fifteen tumors showed feeding arteries. The presence of a feeding artery and the tumor size (<=5 cm) were the predictive factors for a good response (P=0.043 and P=0.047, respectively). CONCLUSIONS: The presence of a feeding artery and a tumor size of less than 5 cm were the predictive factors for a good response of HCC to TACE on CEUS. PMID- 26157754 TI - The usefulness of contrast-enhanced ultrasonography in the early detection of hepatocellular carcinoma viability after transarterial chemoembolization: pilot study. AB - BACKGROUND/AIMS: The therapeutic effect of transarterial chemoembolization (TACE) against hepatocellular carcinoma (HCC) is usually assessed using multidetector computed tomography (MDCT). However, dense lipiodol depositions can mask the enhancement of viable HCC tissue in MDCT. Contrast-enhanced ultrasonography (CEUS) could be effective in detecting small areas of viability and patency in vessels. We investigated whether arterial enhancement in CEUS after treatment with TACE can be used to detect HCC viability earlier than when using MDCT. METHODS: Twelve patients received CEUS, MDCT, and gadoxetic-acid-enhanced dynamic magnetic resonance imaging (MRI) at baseline and 4 and 12 weeks after TACE. The definition of viable HCC was defined as MRI positivity after 4 or 12 weeks. RESULTS: Eight of the 12 patients showed MRI positivity at 4 or 12 weeks. All patients with positive CEUS findings at 4 weeks (n=8) showed MRI positivity and residual viable HCC at 4 or 12 weeks. Five of the eight patients with positive CEUS findings at 4 weeks had negative results on the 4-week MDCT scan. Four (50%) of these eight patients did not have MRI positivity at 4 weeks and were ultimately confirmed as having residual HCC tissue at the 12-week MRI. Kappa statistics revealed near-perfect agreement between CEUS and MRI (kappa=1.00) and substantial agreement between MDCT and MRI (kappa=0.67). CONCLUSIONS: In the assessment of the response to TACE, CEUS at 4 weeks showed excellent results for detecting residual viable HCC, which suggests that CEUS can be used as an early additive diagnosis tool when deciding early additional treatment with TACE. PMID- 26157755 TI - Caroli's disease misdiagnosed as intraductal papillary neoplasm of the bile duct. AB - Caroli's disease is a rare autosomal-recessive disorder caused by malformation of the ductal plate during embryonic development. Although it is present at birth, Caroli's disease is typically not diagnosed until between the second and fourth decades of life, as it was in the present patient. Here we report a rare case of Caroli's disease limited to one liver segment, which was initially misdiagnosed as an intraductal papillary neoplasm of the bile duct. The asymptomatic patient was treated with liver segmentectomy. PMID- 26157756 TI - Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report. AB - Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine. PMID- 26157757 TI - Cholangiolocellular carcinoma with satellite nodules showing intermediate differentiation. PMID- 26157758 TI - Benign nodules mimicking hepatocellular carcinoma on gadoxetic acid-enhanced liver MRI. PMID- 26157759 TI - Prostatic urethral lift: A minimally invasive treatment for benign prostatic hyperplasia. AB - Prostatic urethral lift (PUL) is a minimally invasive procedure for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia. The procedure may be performed under local, spinal, or general anesthesia. The PUL procedure involves the delivery of implants that retract obstructing prostate lobes. Unlike other benign prostatic hyperplasia treatment options including pharmacological therapy, and the current invasive gold-standard transurethral resection of the prostate, the PUL procedure achieves quantifiable improvements in functional outcomes and quality of life, in the absence of major adverse events. Furthermore, improvement in LUTS may be attained while preserving erectile and ejaculatory function. Adverse effects associated with the PUL procedure are mild to moderate, and are transient in nature. The PUL procedure provides an alternative for men seeking treatment for bothersome LUTS, with fewer side-effects. PMID- 26157760 TI - Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer. AB - PURPOSE: To assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife. METHODS: We extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over time, PSA velocity, and PSA nadir were evaluated from the completion of SBRT using CyberKnife. Biochemical recurrence (BCR)-free survival after primary SBRT using CyberKnife was determined using Kaplan-Meier analysis. RESULTS: The rate of PSA decrease was maximal in the first month (median -3.34 ng/mL/mo), which then fell gradually with median values of -1.51, 0.32, -0.28, -0.20, and -0.03 ng/mL/mo for durations of 3, 6, 9, 12, and 24 months after SBRT using CyberKnife, respectively. The median PSA nadir was 0.31 ng/mL after a median 23 months. Kaplan-Meier analysis calculates an actuarial 5 year BCR-free survival after SBRT using CyberKnife as 80.8%. CONCLUSIONS: PSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer. PMID- 26157761 TI - Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels. AB - PURPOSE: Prostate-specific antigen (PSA) is a surrogate marker of disease progression; however, its predictive ability in the extreme ranges is unknown. We determined the predictors of survival in patients with bone metastatic prostate cancer (BMPCa) and with extremely high PSA levels. METHODS: Treatment-naive patients (n = 248) diagnosed with BMPCa between December 2002 and June 2012 were retrospectively analyzed. Clinicopathological features at diagnosis, namely age, body mass index, serum alkaline phosphatase (ALP) and PSA levels, PSA nadir, time to PSA nadir and its maintenance period, PSA declining velocity, Gleason grade, clinical T stage, pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), and the number of bone metastases were assessed. The patients were stratified according to PSA ranges of <20 ng/mL, 20-100 ng/mL, 100-1000 ng/mL, and 1000-10,000 ng/mL. Study endpoints were castration-resistant PCa (CRPC)-free survival and cancer-specific survival (CSS). RESULTS: Patients with higher PSA and ALP levels showed more bone lesions (P < 0.001). During the follow up period (median, 39.9 months; interquartile range, 21.5-65.9 months), there were no differences between the groups in terms of the survival endpoints. High ALP levels, shorter time to PSA nadir, and pain were associated with an increased risk of progression to CRPC, and high ALP levels, ECOG PS >= 1, and higher PSA nadir independently predicted CSS. CONCLUSIONS: PSA response to androgen deprivation therapy and serum ALP are reliable predictors of survival in patients with BMPCa presenting with extremely high PSA levels. These patients should not be deterred from active treatment based on baseline PSA values. PMID- 26157762 TI - Efficacy and safety of degarelix in Korean patients with prostate cancer requiring androgen deprivation therapy: Open-label multicenter phase III study. AB - PURPOSE: To assess the noninferiority, efficacy, and safety of degarelix in achieving and maintaining testosterone at castrate levels (<=0.5 ng/mL) in Korean patients (CS42) versus non-Asian patients with prostate cancer (PCa). METHODS: A Phase III, open-label, multicenter, single-arm trial was conducted in Korean patients with PCa. Degarelix was administered at a starting dose of 240 mg followed by monthly (28-day intervals) maintenance doses of 80 mg (240/80 mg dose regimen) for 7 months. The results were compared with non-Asian patients receiving degarelix 240/80 mg in the CS21 study. RESULTS: The estimated difference in the cumulative probabilities of testosterone <=0.5 ng/mL from Day 28 to Day 196 between the trials was -2.3% (96.7% in CS42 vs. 99.0% in CS21). The lower limit of the 95% confidence interval was -5.5%, i.e., above the predefined noninferiority limit of -10% and thus noninferiority was established. Decreases in serum testosterone, prostate-specific antigen, and luteinizing hormone over time were similar in CS42 and CS21. There were no clinically significant differences in incidence of treatment-emergent adverse events (72% in CS42 vs. 70% in CS21) and changes in clinical chemistry and hematology parameters between the two trials. The most common adverse event was injection-site reaction. CONCLUSIONS: Overall, degarelix was effective and well tolerated in Korean patients. Testosterone suppression was noninferior to that in non-Asian patients and safety findings were as would be expected for elderly men with PCa undergoing androgen deprivation therapy. PMID- 26157763 TI - Long-term outcomes of nonpalpable prostate cancer (T1c) patients treated with radical prostatectomy. AB - PURPOSE: Various strategies have been used to treat patients with nonpalpable prostate cancer (T1c). As one of the treatments for this stage, a radical prostatectomy was performed and the outcomes were evaluated. METHODS: Between 1993 and 2002, 117 patients with T1c received a radical prostatectomy and their follow-up were examined by the end of 2013. Patients were classified according to risk groups using prostate-specific antigen (PSA) and Gleasson score, and outcomes of respective groups were compared. RESULTS: Approximately 60% of patients were in low risk group, and the remaining patients were grouped into the intermediate or high risks in half. In 22% insignificant cancer was detected. Biochemical failure occurred in 14%. One patient exhibited bone metastasis, but no deaths from prostate cancer ware observed. The five and ten year overall survival rates were 92% and 75%, respectively, and the biochemical failure-free survival rates were 92% and 89%, respectively. No different outcomes were observed for the different risk groups in the overall and biochemical failure free survival rates. T1c tumors contain a certain range of various stages of tumors, but most patients experienced favorable outcomes. CONCLUSION: Radical prostatectomy as monotherapy is one of the treatment option for T1c prostate cancer patients, who have a long life span and belong to intermediate or high risk groups. PMID- 26157764 TI - Is an adjustment by transurethral surgery simultaneously needed during the suprapubic open prostatectomy? AB - PURPOSE: To compare suprapubic open prostatectomy (SOP) and a novel SOP with transurethral adjustment of residual adenoma and bleeding (TURARAB) for large sized prostates. METHODS: Between March 2010 and March 2014, 49 patients with symptomatic BPH (>100 g) were scheduled for SOP or SOP with TURARAB. The patients were subdivided into two groups. In Group I, each patient underwent SOP. In Group II, each patient underwent SOP with TURARAB. Additional transurethral resection of residual adenoma and bleeding control were done through the urethra after enucleation of the prostate adenoma by SOP. Prior to intervention, all patients were analyzed by preoperative complete blood count, blood chemistry, prostate specific antigen, International Prostate Symptom Scores, and transrectal ultrasound of the prostate and uroflowmetry. SOP was performed by a suprapubic transvesical approach via a midline incision. The bladder neck mucosa was circularly incised to expose the prostate adenoma, and the plane between the adenoma and surgical capsule was developed by finger dissection. In addition, in Group II TURARAB was performed using Urosol. Postoperative outcome data were compared in the 1st month and 3rd month. RESULTS: There were no statistically significant differences in baseline characteristics between the two groups. Group I required a longer operative time than Group II. Blood transfusion during the operation was unnecessary due to the short amount of time available to control arterial bleeding in the prostatic fossa leading to a marked decrease in perioperative bleeding in Group II. Postoperative voiding function improved significantly in both groups. CONCLUSIONS: Even for large prostate glands, our novel procedure appears to be an effective and safe operation to reduce operation time, bleeding, and complications. PMID- 26157765 TI - Focal therapy for prostate cancer: The current status. AB - PURPOSE: In an era of increasing prostate cancer incidence and earlier detection, the assessment of clinical significance of prostate cancer is critical. Minimally invasive therapies are increasingly being investigated in localized prostate cancer. METHODS AND RESULTS: In this review, we discuss the current status of magnetic resonance imaging targeted fusion prostate biopsy and focal therapy for prostate cancer, its rationale, and techniques. CONCLUSION: Focal therapy offers a promising outlook for prostate cancer treatment, with the goal of effectively achieving cancer control while minimizing morbidity. Long term studies are needed. PMID- 26157766 TI - Docetaxel in very elderly men with metastatic castration-resistant prostate cancer. AB - PURPOSE: To evaluate the use of docetaxel in very elderly men with metastatic castration-resistant prostate cancer (mCRPC) treated in routine clinical care. METHODS: A retrospective case series of men with mCRPC aged >=80 years and treated with docetaxel between July 2006 and June 2012 at three community hospitals in Melbourne, Australia. RESULTS: Twenty patients were identified, with a median age of 83 years (range 80-93 years). Aside from one patient treated weekly, all patients were treated with a 3-weekly regimen of docetaxel with a median of six cycles (range 1-10 cycles) delivered. Eight patients (40%) had an initial dose reduction and 11 patients (55%) had subsequent dose delays or reductions. Eight patients (40%) completed planned treatment. Grade 3/4 hematologic toxicity was observed in nine patients (45%), and five patients (25%) were admitted to hospital with chemotherapy-related complications. Prostate specific antigen (PSA) response was assessable for 16 patients, of whom nine (56%) had a PSA response of >=50% and one (6%) had a PSA-complete response. The median overall survival in this cohort was 13.4 months. CONCLUSIONS: Very elderly patients (80 + years) with mCRPC are infrequently included in clinical trials, yet the use of chemotherapy in this population is likely to increase. Our series demonstrates significant response rates to docetaxel chemotherapy, but that a substantial number of patients had treatment-related complications. This highlights the need for careful patient selection and optimization of chemotherapy dosing. PMID- 26157767 TI - Can robot-assisted radical prostatectomy be taught to chief residents and fellows without affecting operative outcomes? AB - PURPOSE: To determine whether robot-assisted radical prostatectomy (RARP) may be taught to chief residents and fellows without influencing operative outcomes. METHODS: Between August 2011 and June 2012, 388 patients underwent RARP by a single primary surgeon (DIL) at our institution. Our teaching algorithm divides RARP into five stages, and each trainee progresses through the stages in a sequential manner. Statistical analysis was conducted after grouping the cohort according to the surgeons operating the robotic console: attending only (n = 91), attending and fellow (n = 152), and attending and chief resident (n = 145). Approximately normal variables were compared utilizing one-way analysis of variance, and categorical variables were compared utilizing two-tailed chi(2) test; P < 0.05 was considered statistically significant. RESULTS: There was no difference in mean age (P = 0.590), body mass index (P = 0.339), preoperative SHIM (Sexual Health Inventory for Men) score (P = 0.084), preoperative AUASS (American Urologic Association Symptom Score) (P = 0.086), preoperative prostate specific antigen (P = 0.258), clinical and pathological stage (P = 0.766 and P = 0.699, respectively), and preoperative and postoperative Gleason score (P = 0.775 and P = 0.870, respectively). Operative outcomes such as mean estimated blood loss (P = 0.807) and length of stay (P = 0.494) were similar. There was a difference in mean operative time (P < 0.001; attending only = 89.3 min, attending and fellow 125.4 min, and attending and chief resident 126.9 min). Functional outcomes at 3 months and 1 year postoperatively such as urinary continence rate (P = 0.977 and P = 0.720, respectively), and SHIM score (P = 0.661 and P = 0.890, respectively) were similar. The rate of positive surgical margins (P = 0.058) was similar. CONCLUSIONS: Training chief residents and fellows to perform RARP may be associated with increased operative times, but does not compromise short-term functional and oncological outcomes. PMID- 26157768 TI - Importance of cycles of chemotherapy and postdocetaxel novel therapies in metastatic castration-resistant prostate cancer. AB - PURPOSE: With the emergence of various novel therapies including new generation taxane and androgen-targeted therapies, the optimal sequence of systemic treatment in metastatic castration-resistant prostate cancer (mCRPC) patients remains to be defined. Our aim is to investigate the impact of duration of docetaxel-based chemotherapy and postdocetaxel treatment in mCRPC patients. METHODS: The medical data of 57 Chinese mCRPC patients who received docetaxel based chemotherapy in two oncology centers between 2003 and 2012 were reviewed. The treatment efficacy and toxicity were determined. The potential determinants of efficacy were also determined. RESULTS: Fifty-seven patients (median age 66 years, range 51-82 years) were given docetaxel-based chemotherapy, of whom 48 (84.2%) received 3-weekly docetaxel (52.5-75 mg/m(2)) and nine (15.8%) received weekly docetaxel (35 mg/m(2)). Postdocetaxel treatments were received by 31 (57.4%) patients, including abiraterone in 13 patients and cabazitaxel in one patient. The median follow-up time was 14.3 months. The median overall survival (OS) and progression-free survival were 20.8 months and 5.8 months, respectively. In multivariate analysis, eight cycles or more of chemotherapy [hazard ratio (HR) = 0.151, P < 0.0358], use of postdocetaxel treatment (HR = 0.346, P = 0.0005), and hemoglobin level of <10 (HR = 5.224, P < 0.0001) were independent determinants of OS. Patients who had received abiraterone and cabazitaxel as postdocetaxel treatment had significantly longer OS compared with those who received other postdocetaxel treatments (including rechallenge of docetaxel) and those who did not receive any postdocetaxel treatment (35.3 months vs. 20.8 months vs. 15.3 months, P = 0.00057). CONCLUSIONS: The results suggest that maximizing exposure to docetaxel-based chemotherapy followed by novel therapies would have a favorable survival impact on mCRPC patients. PMID- 26157769 TI - Oncologic aspects of long-term followed incidental prostate cancer detected by cystoprostatectomy in Korean patients. AB - PURPOSE: To determine the incidence and clinical features of incidentally discovered prostate adenocarcinoma in patients undergoing radical cystoprostatectomy (CPT) for bladder cancer. METHODS: Ninety-six consecutive patients scheduled to undergo CPT were prospectively enrolled. The prostates were excised completely during CPT. The CPT specimens were examined, and the clinicopathologic characteristics of incidental prostate cancer studied. Complete transverse sections of the prostate were taken from the apex to the base at 4-mm intervals and all prostates were examined by a single pathologist. RESULTS: The mean patient age and prostate-specific antigen level were 66.1 +/- 10.0 years and 2.8 +/- 5.0 ng/mL, respectively. Of the 96 patients, 35 (36.5%) had prostate cancer (PCa). Of these incidental PCas, 57.1% (20.8% of all patients undergoing CPT) were clinically significant. None of the patients who were age <=50 years had incidental PCa. However, the incidences of PCa in the 51-60 years, 61-70 years, and >=71 years age groups were 27.8% (5/18), 48.7% (19/39), and 35.5% (15/31), respectively, and the difference according to the age subgroup was significant (P = 0.048). During the median follow-up of 49 months, 29.2% (28/96) of patients died. There were no PCa-specific deaths, and two patients (2.1%) showed biochemical recurrences. CONCLUSION: Incidental PCas were diagnosed in ~40% of CPT specimens, and ~50% of incidental PCas were clinically significant. During radical CPT in patients aged >=60 years, the possibility of the presence of PCa and the potential oncologic risk of partial prostatectomy during CPT should be remembered. PMID- 26157770 TI - Prostate volume and prostate-specific antigen in men with Parkinson's disease are not different compared to age-matched control group: A prospective, case controlled multicenter study. AB - PURPOSE: Patients with Parkinson's disease (PD) suffer from gait disturbance as well as lower urinary tract symptoms (LUTS). There have been no reports that evaluated the prostate volume (PV) and prostate-specific antigen (PSA) of patients with PD. In this study, we prospectively evaluated PV and PSA in men with PD. METHODS: From May 2009 to January 2012, 60 PD patients and 60 age matched non-PD patients with LUTS enrolled at three centers in Korea. All participants (PD as well as non-PD patients) had LUTS at presentation. We measured the PV using a transrectal ultrasonography and checked the serum PSA level in patients with PD and their non-PD counterparts, who served as the age matched control group, and then compared the data of both groups. Patients with abnormal digital rectal examination results and/or serum PSA levels >4.0 ng/mL underwent prostate biopsy. RESULTS: The mean patient age was 71.37 +/- 7.36 years and 70.85 +/- 6.31 years for PD and non-PD patients (P = 0.651), respectively. There were no significant statistical differences between the two groups in terms of total PV (28.56 +/- 14.59 in PD vs. 29.21 +/- 10.41 in non-PD, P = 0.727), transition zone PV (12.72 +/- 8.76 vs. 12.73 +/- 6.68, P = 0.993), and total serum PSA (1.88 +/- 2.80 vs. 2.01 +/- 2.02, P = 0.759). In the PD group, seven patients had PSA levels >4.0 ng/mL (range, 4.12-11.18 ng/mL). Among these patients, prostate cancer (PC) was detected in two patients. In the non-PD group, PSA levels >4.0 ng/mL were detected in nine patients (range, 4.16-8.28 ng/mL). Among these patients, PC was detected in three patients. The PC occurrence rate was similar in both groups. CONCLUSIONS: Our data show that a neurologic lesion causing PD does not affect PV and PSA. As both groups have a similar PC occurrence rate, it is clear that prostate evaluation is necessary for PD as well as non-PD patients. PMID- 26157771 TI - Prevalence and factor association of premature ejaculation among adult Asian males with lower urinary tract symptoms. AB - PURPOSE: To determine the prevalence of premature ejaculation (PE) among adult Asian males presented with lower urinary tract symptoms (LUTS) and characterize its association with other clinical factors. METHODS: A cross-sectional study was conducted at a tertiary medical center to determine the prevalence of PE among adult male participants with LUTS during the Annual National Prostate Health Awareness Day. Basic demographic data of the participants were collected. All participants were assessed for the presence and severity of LUTS using the International Prostate Symptom Score (IPSS), and for the presence of PE using the PE diagnostic tool. Digital rectal examination was performed by urologists to obtain prostate size. LUTS was further categorized into severity, storage symptoms (frequency, urgency, and nocturia), and voiding symptoms (weak stream, intermittency, straining, and incomplete emptying) to determine their association with PE. Data were analyzed by comparing the participants with PE (PE diagnostic tool score >=11) versus those without PE, using the independent t test for continuous data, Mann-Whitney U test for ordinal data, and Chi-square test for nominal data. The statistical significance was set at P < 0.05. RESULTS: A total of 101 male participants with a mean +/- standard deviation age of 60.75 +/- 10.32 years were included. Among the participants, 33% had moderate LUTS, and 7% severe LUTS. The most common LUTS was nocturia (33%). The overall prevalence of PE was 27%. There was no significant difference among participants with PE versus those without PE in terms of age, marital status, prostate size, or total IPSS score. However, significant difference between groups was noted on the level of education (Mann-Whitney U, z = -1.993, P = 0.046) where high educational status was noted among participants with PE. Likewise, participants with PE were noted to have more prominent weak stream (Mann-Whitney U, z = -2.126, P = 0.033). CONCLUSIONS: Among the participants consulted with LUTS, 27% have concomitant PE. Educational status seems to have an impact in the self-reporting of PE, which may be due to a higher awareness of participants with higher educational attainment. A significant association between PE and weak stream that was not related to prostate size suggests a neuropathologic association. PMID- 26157772 TI - Mesenchymal niche: the sensor and effector of leukemogenesis. PMID- 26157773 TI - Reduced-intensity conditioning hematopoietic stem cell transplantation: looking forward to an international consensus. PMID- 26157774 TI - Gelatinous transformation of the bone marrow in hepatocellular carcinoma. PMID- 26157775 TI - Intraleukocytic hemozoin pigments in complicated Plasmodium falciparum cerebral malaria. PMID- 26157776 TI - Apoptosis: role in myeloid cell development. AB - Hematopoiesis is the process that generates blood cells in an organism from the pluripotent stem cells. Hematopoietic stem cells are characterized by their ability to undergo self-renewal and differentiation. The self-renewing ability ensures that these pluripotent cells are not depleted from the bone marrow niche. A proper balance between cell death and cell survival is necessary to maintain a homeostatic condition, hence, apoptosis, or programmed cell death, is an essential step in hematopoiesis. Recent studies, however, have introduced a new aspect to this process, citing the significance of the apoptosis mediator, caspase, in cell development and differentiation. Extensive research has been carried out to study the possible role of caspases and other apoptosis related factors in the developmental processes. This review focuses on the various apoptotic factors involved in the development and differentiation of myeloid lineage cells: erythrocytes, megakaryocytes, and macrophages. PMID- 26157777 TI - Down-regulation of the autophagy gene, ATG7, protects bone marrow-derived mesenchymal stem cells from stressful conditions. AB - BACKGROUND: Mesenchymal stem cells (MSCs) are valuable for cell-based therapy. However, their application is limited owing to their low survival rate when exposed to stressful conditions. Autophagy, the process by which cells recycle the cytoplasm and dispose of defective organelles, is activated by stress stimuli to adapt, tolerate adverse conditions, or trigger the apoptotic machinery. This study aimed to determine whether regulation of autophagy would affect the survival of MSCs under stress conditions. METHODS: Autophagy was induced in bone marrow-derived MSCs (BM-MSCs) by rapamycin, and was inhibited via shRNA-mediated knockdown of the autophagy specific gene, ATG7. ATG7 expression in BM-MSCs was evaluated by reverse transcription polymerase chain reaction (RT-PCR), western blot, and quantitative PCR (qPCR). Cells were then exposed to harsh microenvironments, and a water-soluble tetrazolium salt (WST)-1 assay was performed to determine the cytotoxic effects of the stressful conditions on cells. RESULTS: Of 4 specific ATG7-inhibitor clones analyzed, only shRNA clone 3 decreased ATG7 expression. Under normal conditions, the induction of autophagy slightly increased the viability of MSCs while autophagy inhibition decreased their viability. However, under stressful conditions such as hypoxia, serum deprivation, and oxidative stress, the induction of autophagy resulted in cell death, while its inhibition potentiated MSCs to withstand the stress conditions. The viability of autophagy-suppressed MSCs was significantly higher than that of relevant controls (P<0.05, P<0.01 and P<0.001). CONCLUSION: Autophagy modulation in MSCs can be proposed as a new strategy to improve their survival rate in stressful microenvironments. PMID- 26157778 TI - Bortezomib inhibits the survival and proliferation of bone marrow stromal cells. AB - BACKGROUND: Bortezomib is widely used for the treatment of multiple myeloma. Bone marrow stromal cells (BMSCs) endow myeloma cells with survival and growth advantages. However, the influence of bortezomib on BMSCs is not well elucidated. We examined the effects of bortezomib on the survival and growth of BMSCs in vitro. METHODS: The effects of bortezomib on the survival and proliferation of the BMSC MS-5 cell line and on BMSCs obtained from healthy individuals (N=4) and newly diagnosed myeloma patients (N=5) were investigated in vitro. Transmembrane cell migration was evaluated using the Transwell system. A short interfering RNA strategy was used to knock down the expression of chemokine (CXC motif) ligand 12 (CXCL12) mRNA. To examine the effects of bortezomib-exposed BMSCs on the migration and localization of myeloma cells, MS-5 monolayers were treated with bortezomib for 24 hr, washed, and then overlaid with human RPMI8226 myeloma cells. RESULTS: Bortezomib inhibited BMSC proliferation in a concentration dependent manner, and induced cellular apoptosis. Bortezomib decreased CXCL12 production by BMSCs. Knockdown of CXCL12 mRNA in BMSCs revealed that CXCL12 served as an autocrine growth factor. Short-term bortezomib treatment of BMSC monolayers reduced the tendency of myeloma cells to locate to positions under the monolayers. CONCLUSION: Bortezomib inhibits the survival and growth of BMSCs via downregulation of CXCL12, which may contribute to the clinical effects of this agent. PMID- 26157779 TI - Maximum standardized uptake value on positron emission tomography/computed tomography predicts clinical outcome in patients with relapsed or refractory diffuse large B-cell lymphoma. AB - BACKGROUND: Few clinical studies have clarified the prognostic factors that affect clinical outcomes for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) after immunochemotherapy. METHODS: A total of 158 patients with relapsed or refractory DLBCL were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) before and after salvage therapy. All enrolled patients previously received the ifosfamide, carboplatin, and etoposide regimen. Clinical outcomes were compared according to several factors (age >= 65 years, low age-adjusted International Prognostic Index [aa IPI], maximum standardized uptake value [SUVmax] <6.0 on PET/CT, time to relapse >=12 months, complete response after salvage therapy). A low aa-IPI, SUVmax <6.0, and time to relapse >= 12 months were independent prognostic factors for survival. RESULTS: In univariate analysis and multivariate analysis, SUVmax below 6.0 (P<0.001 for progression-free survival (PFS), P<0.001 for overall survival (OS)) and low aa-IPI (P<0.001 for PFS, P<0.001 for OS) were independent prognostic factors associated with favorable outcome. CONCLUSION: The aa-IPI and initial SUVmax were powerful prognostic factors in patients with relapsed or refractory DLBCL. PMID- 26157780 TI - Human coagulation factor VIII domain-specific recombinant polypeptide expression. AB - BACKGROUND: Hemophilia A is caused by heterogeneous mutations in F8. Coagulation factor VIII (FVIII), the product of F8, is composed of multiple domains designated A1-A2-B-A3-C1-C2. FVIII is known to interact with diverse proteins, and this characteristic may be important for hemostasis. However, little is known about domain-specific functions or their specific binding partners. METHODS: To determine F8 domain-specific functions during blood coagulation, the FVIII domains A1, A2, A3, and C were cloned from Hep3B hepatocytes. Domain-specific recombinant polypeptides were glutathione S-transferase (GST)- or polyhistidine (His)-tagged, over-expressed in bacteria, and purified by specific affinity chromatography. RESULTS: Recombinant polypeptides of predicted sizes were obtained. The GST-tagged A2 polypeptide interacted with coagulation factor IX, which is known to bind the A2 domain of activated FVIII. CONCLUSION: Recombinant, domain-specific polypeptides are useful tools to study the domain-specific functions of FVIII during the coagulation process, and they may be used for production of domain-specific antibodies. PMID- 26157781 TI - Stability of eosin-5'-maleimide dye used in flow cytometric analysis for red cell membrane disorders. AB - BACKGROUND: The eosin-5'-maleimide (EMA) binding test using flow cytometry is a common method to measure reduced mean channel fluorescence (MCF) of EMA-labeled red blood cells (RBCs) from patients with red cell membrane disorders. The basic principle of the EMA-RBC binding test involves the covalent binding of EMA to lysine-430 on the first extracellular loop of band 3 protein. METHODS: In the present study, the MCF of EMA was analyzed for samples derived from 12 healthy volunteers (controls) to determine the stability (i.e., the percentage decrease in fluorescence) of EMA over a period of 1 year. RESULTS: Comparison of periodical MCF readings over time, that is, at 2-month intervals, showed that there were no significant changes in mean channel fluorescence for up to 6 months; however, there was a significant decrease in MCF at 8 months. CONCLUSION: For optimal dye utilization, EMA remained stable only for up to 6 months. Therefore, we recommend reconstitution of the dye every 6 months when implementing this test and storage at -80C in dark conditions. PMID- 26157782 TI - Successful re-treatment with azacitidine in a patient with low blast count AML transformed from MDS after suspension of this agent. PMID- 26157783 TI - Prevalent factor XII deficiency in cancer patients with isolated aPTT prolongation. PMID- 26157784 TI - Pseudo gray platelet syndrome: the first case report in Korea. PMID- 26157785 TI - New approaches for cholestasis in hemoglobinopathies. PMID- 26157786 TI - Opsismodysplasia: Phosphate Wasting Osteodystrophy Responds to Bisphosphonate Therapy. AB - We present two siblings affected with opsismodysplasia (OPS), a rare skeletal dysplasia caused by mutations in the inositol polyphosphate phosphatase-like 1 gene. The skeletal findings include short stature with postnatal onset micromelia, marked platyspondyly, squared metacarpals, delayed skeletal ossification, metaphyseal cupping, and postnatal micromelia. Respiratory compromise, delayed ambulation, and progressive lower extremity deformities are described. The severity of findings is variable. Renal phosphate wasting is associated with severe bone demineralization and a more severe phenotype. This report represents the first described cases of opsismodysplasia treated with intravenous bisphosphonate (pamidronate). Surgical management for lower extremity deformities associated with OPS is also reviewed. LEVEL OF EVIDENCE: IV Case series. PMID- 26157788 TI - Improving Pediatric Cancer Care Disparities Across the United States-Mexico Border: Lessons Learned from a Transcultural Partnership between San Diego and Tijuana. AB - In 2007, the 5-year survival rate for children with acute leukemia in Baja California, Mexico was estimated at 10% (vs. 88% in the United States). In response, stakeholders at St. Jude Children's Research Hospital, Rady Children's Hospital San Diego, and the Hospital General de Tijuana (HGT) implemented a transcultural partnership to establish a pediatric oncology program. The aim was to improve clinical outcomes and overall survival for children in Baja California. An initial needs assessment evaluation was performed and a culturally sensitive, comprehensive, 5-year plan was designed and implemented. After six years, healthcare system accomplishments include the establishment of a fully functional pediatric oncology unit with 60 new healthcare providers (vs. five in 2007). Patient outcome improvements include a rise in 5-year survival for leukemia from 10 to 43%, a rise in new cases diagnosed per year from 21 to 70, a reduction in the treatment abandonment rate from 10% to 2%, and a 45% decrease in the infection rate. More than 600 patients have benefited from this program. Knowledge sharing has taken place between teams at the HGT and Rady Children's Hospital San Diego. Further, one of the most significant outcomes is that the HGT has transitioned into a regional referral center and now mentors other hospitals in Mexico. Our results show that collaborative initiatives that implement long term partnerships along the United States-Mexico border can effectively build local capacity and reduce the survival gap between children with cancer in the two nations. Long-term collaborative partnerships should be encouraged across other disciplines in medicine to further reduce health disparities across the United States-Mexico border. PMID- 26157789 TI - Assessing the Education and Training Needs of Nebraska's Public Health Workforce. AB - INTRODUCTION: In 2012, the Great Plains Public Health Training Center (Grant #UB6HP22821) conducted an online survey of state and local health departments and the American Indian (tribal clinics, tribal health departments, and urban Indian clinic) public health workforce across three professional levels. The objectives of the needs assessment were to determine the competency levels of the state's public health workforce, assess gaps in public health competencies, identify public health training interests, needs, and preferences, and to determine the barriers and motivators to participate in public health training. METHODS: The assessment was developed using the Council on Linkages Between Academia and Public Health Practice, Core Competencies for Public Health Professionals survey (1). The final assessment was created and piloted by numerous individuals representing practice and academia. RESULTS: Respondents identified cultural competency and communication skills as the two most important public health competency domains. Although the public health professionals perceived that they were least proficient in the area of policy development and program planning, participants identified the greatest needs for training in financial planning and management skills and analytical/assessment skills. In general, respondents preferred instructor-led interactive training sessions offered as onsite multi day workshops or computer-based courses. Respondents identified obesity, health disparities, physical activity, chronic diseases, and diabetes as the top five public health topical areas. CONCLUSION: These priorities align with State and National public health plans. The findings of the needs assessment were used to tailor educational opportunities to build the capacity of Nebraska's public health system. Additionally, the results were used to develop workforce development plans for numerous local health departments throughout Nebraska. PMID- 26157787 TI - Hypoxic Conditioning as a New Therapeutic Modality. AB - Preconditioning refers to a procedure by which a single noxious stimulus below the threshold of damage is applied to the tissue in order to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic preconditioning relies on complex and active defenses that organisms have developed to counter the adverse consequences of oxygen deprivation. The protection it confers against ischemic attack for instance as well as the underlying biological mechanisms have been extensively investigated in animal models. Based on these data, hypoxic conditioning (consisting in recurrent exposure to hypoxia) has been suggested a potential non-pharmacological therapeutic intervention to enhance some physiological functions in individuals in whom acute or chronic pathological events are anticipated or existing. In addition to healthy subjects, some benefits have been reported in patients with cardiovascular and pulmonary diseases as well as in overweight and obese individuals. Hypoxic conditioning consisting in sessions of intermittent exposure to moderate hypoxia repeated over several weeks may induce hematological, vascular, metabolic, and neurological effects. This review addresses the existing evidence regarding the use of hypoxic conditioning as a potential therapeutic modality, and emphasizes on many remaining issues to clarify and future researches to be performed in the field. PMID- 26157790 TI - Freshman College Students' Reasons for Enrolling in and Anticipated Benefits from a Basic College Physical Education Activity Course. AB - BACKGROUND: Given the rise in US obesity rates in adulthood, efforts are needed to assess physical activity engagement during the college years as a strategy to promote a lifetime of being physically active. This study identifies the reasons incoming college freshman enrolled in basic physical education activity courses (BPEAC) and the perceived benefits they anticipated receiving as a result of course participation. METHODS: Data collected from 302 college freshmen in September 2013 were analyzed. A paper-based questionnaire was administered to 78% of BPEAC sections offered at a large Southeastern University. Frequencies were presented for all participants, which were then compared by sex and course type. Kappa statistics were calculated to examine the concordance between participants' reasons for enrolling in the course and the benefits they anticipated from course enrollment. RESULTS: Diverse physical, mental, social, and academic reasons for enrolling in BPEAC were reported by study participants. Varied anticipated benefits from course participation were reported as well. Reported enrollment reasons and anticipated benefits differed by sex and course type. High concordance between matched enrollment reasons and anticipated benefits was observed. CONCLUSION: Implications highlight the need for universities to provide quality BPEAC, promote high-quality instruction, and offer a wide variety of physical education courses to meet the diverse needs of students. PMID- 26157791 TI - Structural Vulnerability Among Migrating Women and Children Fleeing Central America and Mexico: The Public Health Impact of "Humanitarian Parole". AB - Since October 2013, US Customs and Border Patrol has apprehended 15,979 families on the Southwest Border of the US. Daily, migrating women and children from Mexico and Central America that qualify for humanitarian parole are released from immigration detention to a humanitarian aid organization in Southern Arizona. After several days in detention facilities, these families arrive tired, hungry, dehydrated, and with minimal direction regarding their final destination, and adherence to the parameters of their parole. Project helping hands (PHHs) utilizes a network of volunteers to provide the women and children with food, water, clothing, hygiene products, hospitality, and legal orientation. The aim of this assessment was to document the experiences of families granted humanitarian parole through the lens of structural vulnerability. Here, we apply qualitative methods to elicit PHH lead volunteer perspectives regarding the migration experience of migrating families. Using inductive analysis, we found six major themes emerged from the qualitative data: reasons for leaving, experience on the journey, dehumanization in detention, family separation, vulnerability, and resiliency. These findings elucidate the different physical and psychological distresses that migrating families from Mexico and Central America experience before, during and after their arrival at the US-Mexico border. We posit that these distresses are a result of, or exacerbated by, structural vulnerability. Structural vulnerability has life-long health implications for a sub-population of young mothers and their children. The number of migrating families who have experienced traumatic events before and during their migration experience continues to expand and thus warrants consideration of mental health surveillance and intervention efforts for these families. More public health research is needed to better understand and combat the health challenges of this growing population. PMID- 26157792 TI - Economic Evaluation Enhances Public Health Decision Making. AB - Contemporary public health professionals must address the health needs of a diverse population with constrained budgets and shrinking funds. Economic evaluation contributes to evidence-based decision making by helping the public health community identify, measure, and compare activities with the necessary impact, scalability, and sustainability to optimize population health. Asking "how do investments in public health strategies influence or offset the need for downstream spending on medical care and/or social services?" is important when making decisions about resource allocation and scaling of interventions. PMID- 26157793 TI - Commentary: "Estrogenic and Anti-Androgenic Endocrine Disrupting Chemicals and Their Impact on the Male Reproductive System". PMID- 26157795 TI - CNS active O-linked glycopeptides. AB - Naturally occurring glycopeptides and glycoproteins play important roles in biological processes. Glycosylation is one of the most common post-translational modifications in vivo. Glycopeptides are involved in cell signaling and sorting, providing cell surface markers for recognition. From the drug design and synthesis perspective, modification of a peptide through glycosylation results in increased bioavailability and bioactivity of glycopeptides in living systems with negligible toxicity of degradation products. Glycopeptide synthesis can be accomplished through incorporation of a glycosylated amino acid in solid phase peptide synthesis (SPPS) to form the desired peptide, or via incorporation of sugar-amino acid moieties. Additionally, research indicates that glycosylation increases penetration of the blood-brain barrier (BBB) by peptides, which may lead to novel therapeutics for neurological disorders. Recent applications of glycopeptides have focused on the in vivo central nervous system (CNS) effects after peripheral administration of centrally active peptides modified with various carbohydrates. PMID- 26157796 TI - Tissue Engineering of Ureteral Grafts: Preparation of Biocompatible Crosslinked Ureteral Scaffolds of Porcine Origin. AB - The surgical reconstruction of ureteric defects is often associated with post operative complications and requires additional medical care. Decellularized ureters originating from porcine donors could represent an alternative therapy. Our aim was to investigate the possibility of manufacturing decellularized ureters, the characteristics of the extracellular matrix (ECM) and the biocompatibility of these grafts in vitro/in vivo after treatment with different crosslinking agents. To achieve these goals, native ureters were obtained from pigs and were decellularized. The success of decellularization and the ECM composition were characterized by (immuno)histological staining methods and a DNA assay. In vitro: scaffolds were crosslinked either with carbodiimide (CDI), genipin (GP), glutaraldehyde, left chemically untreated or were lyophilized. Scaffolds in each group were reseeded with Caco2, LS48, 3T3 cells, or native rat smooth muscle cells (SMC). After 2 weeks, the number of ingrown cells was quantified. In vivo: crosslinked scaffolds were implanted subcutaneously into rats and the type of infiltrating cells were determined after 1, 9, and 30 days. After decellularization, scaffold morphology and composition of ECM were maintained, all cellular components were removed, DNA destroyed and strongly reduced. In vitro: GP and CDI scaffolds revealed a higher number of ingrown 3T3 and SMC cells as compared to untreated scaffolds. In vivo: at day 30, implants were predominantly infiltrated by fibroblasts and M2 anti-inflammatory macrophages. A maximum of MMP3 was observed in the CDI group at day 30. TIMP1 was below the detection limit. In this study, we demonstrated the potential of decellularization to create biocompatible porcine ureteric grafts, whereas a CDI crosslink may facilitate the remodeling process. The use of decellularized ureteric grafts may represent a novel therapeutic method in reconstruction of ureteric defects. PMID- 26157797 TI - Bioinformatics and Moonlighting Proteins. AB - Multitasking or moonlighting is the capability of some proteins to execute two or more biochemical functions. Usually, moonlighting proteins are experimentally revealed by serendipity. For this reason, it would be helpful that Bioinformatics could predict this multifunctionality, especially because of the large amounts of sequences from genome projects. In the present work, we analyze and describe several approaches that use sequences, structures, interactomics, and current bioinformatics algorithms and programs to try to overcome this problem. Among these approaches are (a) remote homology searches using Psi-Blast, (b) detection of functional motifs and domains, (c) analysis of data from protein-protein interaction databases (PPIs), (d) match the query protein sequence to 3D databases (i.e., algorithms as PISITE), and (e) mutation correlation analysis between amino acids by algorithms as MISTIC. Programs designed to identify functional motif/domains detect mainly the canonical function but usually fail in the detection of the moonlighting one, Pfam and ProDom being the best methods. Remote homology search by Psi-Blast combined with data from interactomics databases (PPIs) has the best performance. Structural information and mutation correlation analysis can help us to map the functional sites. Mutation correlation analysis can only be used in very specific situations - it requires the existence of multialigned family protein sequences - but can suggest how the evolutionary process of second function acquisition took place. The multitasking protein database MultitaskProtDB (http://wallace.uab.es/multitask/), previously published by our group, has been used as a benchmark for the all of the analyses. PMID- 26157794 TI - Cysteine cathepsins: their role in tumor progression and recent trends in the development of imaging probes. AB - Papain-like cysteine proteases bear an enormous potential as drug discovery targets for both infectious and systemic human diseases. The considerable progress in this field over the last two decades has also raised interest in the visualization of these enzymes in their native context, especially with regard to tumor imaging. After a short introduction to structure and general functions of human cysteine cathepsins, we highlight their importance for drug discovery and development and provide a critical update on the current state of knowledge toward their involvement in tumor progression, with a special emphasis on their role in therapy response. In accordance with a radiopharmaceutical point of view, the main focus of this review article will be the discussion of recently developed fluorescence and radiotracer-based imaging agents together with related molecular probes. PMID- 26157798 TI - Capture, Unfolding, and Detection of Individual tRNA Molecules Using a Nanopore Device. AB - Transfer RNAs (tRNA) are the most common RNA molecules in cells and have critical roles as both translators of the genetic code and regulators of protein synthesis. As such, numerous methods have focused on studying tRNA abundance and regulation, with the most widely used methods being RNA-seq and microarrays. Though revolutionary to transcriptomics, these assays are limited by an inability to encode tRNA modifications in the requisite cDNA. These modifications are abundant in tRNA and critical to their function. Here, we describe proof-of concept experiments where individual tRNA molecules are examined as linear strands using a biological nanopore. This method utilizes an enzymatically ligated synthetic DNA adapter to concentrate tRNA at the lipid bilayer of the nanopore device and efficiently denature individual tRNA molecules, as they are pulled through the alpha-hemolysin (alpha-HL) nanopore. Additionally, the DNA adapter provides a loading site for phi29 DNA polymerase (phi29 DNAP), which acts as a brake on the translocating tRNA. This increases the dwell time of adapted tRNA in the nanopore, allowing us to identify the region of the nanopore signal that is produced by the translocating tRNA itself. Using adapter-modified Escherichia coli tRNA(fMet) and tRNA(Lys), we show that the nanopore signal during controlled translocation is dependent on the identity of the tRNA. This confirms that adapter-modified tRNA can translocate end-to-end through nanopores and provide the foundation for future work in direct sequencing of individual transfer RNA with a nanopore-based device. PMID- 26157799 TI - How to build personalized multi-omics comorbidity profiles. AB - Multiple diseases (acute or chronic events) occur together in a patient, which refers to the disease comorbidities, because of the multi ways associations among diseases. Due to shared genetic, molecular, environmental, and lifestyle-based risk factors, many diseases are comorbid in the same patient. Methods for integrating multiple types of omics data play an important role to identify integrative biomarkers for stratification of patients into groups with different clinical outcomes. Moreover, integrated omics and clinical information may potentially improve prediction accuracy of disease comorbidities. However, there is a lack of effective and efficient bioinformatics and statistical software for true integrative data analysis. With the availability of the wide spread huge omics, phenotype and ontology information, it is becoming more and more practical to help doctors in clinical diagnostics and comorbidity prediction by providing appropriate software tool. We developed an R software POGO to compute novel estimators of the disease comorbidity risks and patient stratification. Starting from an initial diagnosis, omics and clinical data of a patient the software identifies the association risk of disease comorbidities. The input of this software is the initial diagnosis of a patient and the output provides evidence of disease comorbidities. The functions of POGO offer flexibility for diagnostic applications to predict disease comorbidities, and can be easily integrated to high-throughput and clinical data analysis pipelines. POGO is compliant with the Bioconductor standard and it is freely available at www.cl.cam.ac.uk/~mam211/POGO/. PMID- 26157800 TI - Endometriosis and Vesico-Sphincteral Disorders. AB - OBJECTIVES: The aim of this mini review is to determine the relationship between endometriosis and urinary tract symptoms and to investigate the consequences of surgical treatment of mild to severe endometriosis, especially deep lesions, on the vesico-sphincteral function (lower urinary tract function). MATERIALS AND METHODS: We performed a literature review by searching the MEDLINE database for articles published between 2000 and 2014, limiting the searches to the words: urinary tract, vesico-sphincteral, dysfunction, endometriosis, symptoms, and surgery. RESULTS: The incidence of vesico-sphincteral symptoms in endometriosis varies from 3.4 up to 15.4%. The frequency of such symptoms seems to be under estimated because of a lack of specific questionnaire including urinary symptoms. Urodynamic evaluation could help to detect unsuspected abnormalities. It seems that endometriosis surgery (particularly deep infiltrating lesions) is a purveyor of de novo urinary dysfunction, with an incidence varying from 6.8 up to 17.5%. Nerve sparing processes such as neuro-navigators or neuro-stimulators seem to be promising techniques to avoid postoperative urinary tract dysfunction. CONCLUSION: A precise anamnesis and the use of specific validated questionnaires (IPSS and BFLUTS) improve the screening of vesico-sphincteral symptoms in case of endometriosis. No recommendation can be found in the literature about the place of urodynamic evaluation. Most publications lack of proof and therefore do not allow making recommendations about optimal treatment of endometriotic lesions to avoid urinary tract disorders. PMID- 26157801 TI - Structural modeling of the N-terminal signal-receiving domain of IkappaBalpha. AB - The transcription factor nuclear factor-kappaB (NF-kappaB) exerts essential roles in many biological processes including cell growth, apoptosis and innate and adaptive immunity. The NF-kappaB inhibitor (IkappaBalpha) retains NF-kappaB in the cytoplasm and thus inhibits nuclear localization of NF-kappaB and its association with DNA. Recent protein crystal structures of the C-terminal part of IkappaBalpha in complex with NF-kappaB provided insights into the protein-protein interactions but could not reveal structural details about the N-terminal signal receiving domain (SRD). The SRD of IkappaBalpha contains a degron, formed following phosphorylation by IkappaB kinases (IKK). In current protein X-ray structures, however, the SRD is not resolved and assumed to be disordered. Here, we combined secondary structure annotation and domain threading followed by long molecular dynamics (MD) simulations and showed that the SRD possesses well defined secondary structure elements. We show that the SRD contains 3 additional stable alpha-helices supplementing the six ARDs present in crystallized IkappaBalpha. The IkappaBalpha/NF-kappaB protein-protein complex remained intact and stable during the entire simulations. Also in solution, free IkappaBalpha retains its structural integrity. Differences in structural topology and dynamics were observed by comparing the structures of NF-kappaB free and NF-kappaB bound IkappaBalpha-complex. This study paves the way for investigating the signaling properties of the SRD in the IkappaBalpha degron. A detailed atomic scale understanding of molecular mechanism of NF-kappaB activation, regulation and the protein-protein interactions may assist to design and develop novel chronic inflammation modulators. PMID- 26157803 TI - A New ACG Journal is Born. PMID- 26157804 TI - Massive Gastric Dilatation Secondary to Internal Hernia Obstructing the Biliary Intestinal Limb of Whipple Procedure. PMID- 26157802 TI - Applications of hydrogen deuterium exchange (HDX) for the characterization of conformational dynamics in light-activated photoreceptors. AB - Rational design of optogenetic tools is inherently linked to the understanding of photoreceptor function. Structural analysis of elements involved in signal integration in individual sensor domains provides an initial idea of their mode of operation, but understanding how local structural rearrangements eventually affect signal transmission to output domains requires inclusion of the effector regions in the characterization. However, the dynamic nature of these assemblies renders their structural analysis challenging and therefore a combination of high and low-resolution techniques is required to appreciate functional aspects of photoreceptors. This review focuses on the potential of hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) for complementing the structural characterization of photoreceptors. In this respect, the ability of HDX-MS to provide information on conformational dynamics and the possibility to address multiple functionally relevant states in solution render this methodology ideally suitable. We highlight recent examples demonstrating the potential of HDX-MS and discuss how these results can help to improve existing optogenetic systems or guide the design of novel optogenetic tools. PMID- 26157805 TI - Small Bowel Metastasis from Renal Cell Carcinoma Identified on Capsule Endoscopy. PMID- 26157806 TI - Embedded Fishhook in the Gastric Cardia: Novel Removal Utilizing Electrocautery Needle-Knife Dissection. AB - Foreign body ingestions often consist of benign objects that will readily pass through the gastrointestinal tract (GI) without necessitating further intervention. While several retrieval devices and techniques are available to the endoscopist, we present a novel method of implementing a needle-knife sphincterotome in the removal of an ingested fishhook embedded in the gastric cardia of a 36-year-old man with underlying schizophrenia. The hook was successfully dissected from the gastric submucosa after several unsuccessful attempts at manual extraction with forceps. To our knowledge, our case represents one in only a handful of other reports of the successful removal of ingested foreign bodies utilizing this method. PMID- 26157807 TI - Hemospray for Life-Threatening Ulcer Bleeding: First Case Report in the United States. AB - A 13-year-old boy with metastatic rhabdomyosarcoma presented with biliary obstruction requiring ERCP for stent placement. Re-evaluation after recurrence of symptoms revealed external migration of the stent with formation of a contralateral wall bleeding duodenal ulcer. Endoscopic therapy was not feasible and bleeding persisted despite medical therapy and embolization. Given his life threatening condition, approval for the use of Hemospray (Cook Medical, Winston Salem, NC, USA) was obtained. Hemospray was applied to the visualized bleeding sites with subsequent hemostasis. Patient tolerated the procedure well. This is the first use of Hemospray in the United States outside of a clinical trial. PMID- 26157808 TI - Endoscopic Mucosal Resection of a Large Gastric Metastasis from Renal Cell Carcinoma. AB - Gastric metastasis from renal cell carcinoma (RCC) occurs in less than 1% of cases. A variety of management options have been described for this condition, however, total or partial gastrecomy is the most common therapeutic approach. We present a case of a large gastric metastatic lesion from a RCC diagnosed 10 years before. This was treated with endoscopic mucosal resection (EMR) without evidence of residual lesion after 10 months of follow-up. PMID- 26157809 TI - Iron Pill-Induced Gastritis. AB - Iron-deficiency anemia is a prevalent condition treated with iron supplementation. Iron pill-induced gastritis is an under-recognized, albeit serious potential complication of iron pill ingestion. This entity must be identified by healthcare providers who prescribe iron. We present a case of a 59 year-old male with iron deficiency anemia on ferrous sulfate tablets who underwent an upper endoscopy, during which a single superficial gastric ulceration in the body was noted. Biopsies revealed heavy iron deposition confirming the ulceration was a consequence of the iron tablets. Iron pill induced gastritis causes corrosive mucosal injury similar to that caused by chemical burns. PMID- 26157810 TI - A Case of Persistent Helicobacter pylori Infection Occurring with Anti-IgE Immunosuppression. AB - The increasingly widespread use of novel immunosuppressive drugs may lead to unexpected infectious complications. We report a case of persistent Helicobacter pylori (H. pylori) infection that failed to respond to antimicrobial therapy in a patient receiving omalizumab (XolairTM, Genentech USA Inc., San Francisco, CA and Novartis Pharmaceuticals, Basel, Switzerland), an anti-IgE monoclonal antibody approved by the FDA for treatment of severe persistent asthma. To our knowledge, this is the first case report linking an immunosuppressive regimen containing anti-IgE biologic therapy to persistent H. pylori infection. PMID- 26157811 TI - Kaposi's Sarcoma: An Unusual Cause of Gastric Outlet Obstruction. AB - Kaposi's sarcoma (KS) is the most common AIDS-related neoplasm and is one of the AIDS-defining illnesses. It most frequently presents with cutaneous lesions, but may also involve organ systems. Most cases of gastrointestinal (GI) involvement are clinically silent and found incidentally on imaging studies or endoscopy. Sole involvement of the GI tract can be seen with or without cutaneous disease; however, the latter has been reported as rare by some investigators. We report a case of a 25-year-old man with HIV who presented with gastric outlet obstruction (GOO) and disseminated GI involvement by KS. PMID- 26157812 TI - Intestinal Pseudo-Obstruction and Total Villous Atrophy of the Terminal Ileum: An Unusual Presentation of Untreated Celiac Disease. AB - Intestinal pseudo-obstruction (IPO) is a rare complication of celiac disease (CD) and has often resulted in laparotomy for diagnosis. We report an adult case of CD presenting as IPO with severe protein calorie malnutrition (PCM) and negative endomysial as well as tissue transglutaminase antibodies. This is the first case report of CD presenting with combined IPO, severe PCM, negative first-line celiac serologies, and terminal ileal atrophy that was diagnosed without laparotomy. A non-surgical diagnosis was achieved by expanded laboratory and endoscopic methods, including video capsule endoscopy. Extent of pathologic gut involvement and response to treatment with budesonide and gluten-free diet is described. PMID- 26157813 TI - Nearly Fatal Case of Whipple's Disease in a Patient Mistakenly on Anti-TNF Therapy. AB - Whipple's disease is a rare cause of chronic diarrhea and abdominal pain that may be confused with inflammatory bowel disease. We report a Whipple's case misdiagnosed as Crohn's disease in which treatment with anti-tumor necrosis factor (anti-TNF) therapy led to nearly fatal progression. Lymph node tissue obtained during laparotomy for suspected bowel necrosis stained dramatically with periodic acid-Schiff (PAS), and electron microscopy showed a bacterium consistent with Trophyrema whipplei. The patient made a remarkable recovery complicated only by cholestatic hepatitis, which was likely a treatment-associated inflammatory response. This case serves as a reminder that all granulomatous infections should be considered prior to initiation of anti-TNF therapies. PMID- 26157814 TI - True versus Pseudo-Intestinal Malrotation: Case Series and Review. AB - Intestinal malrotation is an anomaly of fetal intestinal rotation that can present with symptoms after birth or in early childhood, but is rarely diagnosed in adults. Patients who have symptomatic presentations require surgery. Other entities may mimic intestinal malrotation and respond to non-surgical management. We present 2 adult cases with the radiological diagnosis of intestinal malrotation: one with true malrotation presenting as a duodenal mass, and another with "pseudo-malrotation" due to altered anatomy. These cases illustrate the importance of recognizing and differentiating these rare adult presentations of true malrotation from "pseudo-malrotation" in regards to their acute management. PMID- 26157815 TI - Beware of the Patient with Thymectomy: Good's Syndrome in a Patient Presenting with Diarrhea. AB - Good's syndrome is a rare cause of immunodeficiency in adults associated with thymoma. We describe an 80-year-old female with chronic diarrhea, multiple opportunistic infections, and cytopenias. She underwent a thymectomy 5 years ago for a thymoma. Laboratory tests revealed neutropenia, hypogammaglobulinaemia, complete B-cell lymphopenia, and low CD4 T cells with inverted CD4:CD8 ratio, which is consistent with Good's syndrome. We recommend checking immunoglobulin levels in all patients with a history of thymoma. Good's syndrome should be considered as a differential diagnosis if patients present with chronic diarrhea, cytopenias, or recurrent infections. Cytomegalovirus (CMV) infection should be considered in patients with immune deficiency as a cause of chronic diarrhea. PMID- 26157816 TI - Giant Inflammatory Fibroid Polyp of the Descending Colon Treated with Endoscopic Resection. AB - Inflammatory fibroid polyps (IFPs) of the colon are very rare, reactive, non neoplastic polyps that may grow to large sizes but do not carry any risk of malignancy. Because of their size, IFPs are usually treated with surgery; however, size alone should not be an indication for surgery. Depending on the location and morphology of the polyp, endoscopic resection should be considered. We here describe a case of a giant IFP that was successfully removed with endoscopy without complication or recurrence. PMID- 26157817 TI - Not Your Everyday Case of Acute Pancreatitis: A Rare Complication of a Common Diagnosis. AB - Pancreaticopericardial fistula is an extremely rare complication of chronic pancreatitis and is virtually unheard of in the setting of acute pancreatitis. A 67-year-old male presented with acute pancreatitis complicated by pancreaticopericardial fistulization. The patient's initial presentation was consistent with tamponade physiology. Computed tomography demonstrated a gas containing pericardial fluid llection extending into the anterior upper abdomen and ill-defined fluid collections within the pancreas representing necrosis with probable infection. Surgical exploration of the window revealed a pancreatic pericardial fistula and an infected window. The patient ultimately passed away from septic shock. We present this rare complication of pancreatitis and review the relevant literature. PMID- 26157818 TI - Portal Biliopathy Causing Recurrent Biliary Obstruction and Hemobilia. AB - A 63-year-old man with extrahepatic portal vein thrombosis presented with biliary obstruction and hemobilia after a liver biopsy. Balloon sweep of the common bile duct removed clotted blood, and cholangiogram showed a common bile duct narrowing, treated with biliary stenting. A percutaneous biliary catheter was later required for recurrent biliary obstruction and hemobilia, and repeat cholangiogram confirmed portal biliopathy-a large peri-biliary varix was compressing the common bile duct, causing biliary obstruction and intermittent portal hypertensive hemobilia. A transjugular intrahepatic portosystemic shunt was inserted, followed by embolization of the peri-biliary varix. Delayed diagnosis of portal biliopathy may lead to significant patient morbidity. PMID- 26157819 TI - Minor Papilla Adenoma Management in Patients with Pancreas Divisum and Familial Adenomatous Polyposis. AB - Several case reports on endoscopic resection of minor papilla adenomas exist in the literature. However, there are no reported cases of endoscopic resection in patients with minor papilla adenomas with associated familial adenomatous polyposis (FAP) and pancreas divisum. We report a case of a minor papilla adenoma in a patient with FAP and pancreas divisum. The case demonstrates a new association between these disease processes. Defining pancreatic ductal anatomy prior to endoscopic intervention is essential. In addition, we demonstrate the safety and feasibility of endoscopic management of minor papilla tumors in patients with FAP and associated pancreas divisum. PMID- 26157820 TI - Emphysematous Cholecystitis Resulting in Secondary Biliary Cirrhosis: A Rare Complication of Endoscopic Retrograde Cholangiopancreatography. AB - A 48-year-old female developed acute emphysematous cholecystitis after an endoscopic retrograde cholangiopancreatography (ERCP) for evaluation of sphincter of Oddi dysfunction. Cholecystectomy was performed 2 days later. Cultures grew Clostridium perfringens. The patient received broad-spectrum antibiotics but developed recurrent cholangitic abscesses and intra- and extra-hepatic biliary necrosis. She was managed by percutaneous transhepatic biliary drains. For next 3 years, patient had recurrent episodes of biliary obstruction, cholangitis, and sepsis, resulting in secondary biliary cirrhosis requiring a liver transplantation. Emphysematous cholecystitis is a rare complication of ERCP. Prompt diagnosis and surgical management can prevent further spread of infection to biliary tree. PMID- 26157821 TI - Hepatotoxicity Associated with Herbal Tea Containing Kelp. AB - A 40-yr-old Sri Lankan female presented to the gastroenterology clinic with jaundice. Further work-up revealed extrahepatic cholestasis with a hepatocellular component; however, subsequent work-up revealed no significant findings. Hospitalization revealed hepatotoxicity associated with ingestion of a homemade herbal tea containing kelp (Laminaria), which was confirmed with further history. Hepatotoxicity associated with herbal tea ingestion is rare, but should be a consideration in patients with unexplained jaundice. Inquiries into dietary or herbal supplements should always be made during routine history taking, as it may be useful in achieving the diagnosis. PMID- 26157822 TI - Tea not Tincture: Hepatotoxicity Associated with Rooibos Herbal Tea. AB - A 52-year-old male presented with signs of acute hepatitis and liver failure. Laboratory investigations for common etiologies were unrevealing, but history suggested liver injury secondary to ingestion of a traditional South African herbal tea made with rooibos and buchu. Livery biopsy confirmed a toxin-mediated liver injury. The patient recovered liver function after stopping the herbal tea. Although hepatotoxicity associated with rooibos and buchu has rarely been reported, anecdotal correspondence with South African physicians confirmed suspected cases. Hepatotoxicity may be due to the heterogeneous composition of herbal teas due to small-batch manufacturing. Our case clearly outlines the need to suspect herbal causes of idiopathic liver injury. PMID- 26157823 TI - Visceral Leishmania as Unusual Cause of Splenic Peliosis in the United States. AB - A 3-year-old female presented with splenomegaly and hypersplenism manifestations, including anemia, thrombocytopenia, and abdominal pain/distention. All common metabolic, hematologic, gastrointestinal, and infectious etiologies for splenomegaly were excluded. Diagnosis of idiopathic splenic peliosis was made and splenectomy was recommended. History revealed that the patient's mother had acquired a nonspecific skin infection during a visit to the Middle East 2 years prior. Serum antibodies and confirmatory PCR testing for visceral leishmaniasis were positive. After treatment with liposomal amphotericin, at 6-month follow-up her hypersplenism manifestations had resolved and her splenomegaly had significantly decreased. Visceral leishmaniasis should be considered in cases of marked splenomegaly, anemia, and thrombocytopenia, especially with a history of visiting an endemic area. PMID- 26157825 TI - Editor's Note. PMID- 26157824 TI - Conjugated Hyperbilirubinemia in a Child with Streptococcus pneumoniae-associated Hemolytic Uremic Syndrome. AB - Conjugated hyperbilirubinemia is a rare complication of hemolytic uremic syndrome (HUS). We report a case of a 2-year-old female with Streptococcus pneumonia associated HUS (SP+ HUS) who developed severe cholestasis. It is important for pediatric gastroenterologists to be aware of manifestations of HUS, and that although rare, cholestasis can be one of the early findings in patients with SP+ HUS. PMID- 26157826 TI - Unexpected Capsule Endoscopy Images Reveal Aspiration. PMID- 26157827 TI - Chilaiditi's Sign: A Rare Cause of Abdominal Pain. PMID- 26157829 TI - A Rare Case of Childhood Undifferentiated Embryonal Sarcoma of the Liver Managed Successfully. PMID- 26157828 TI - Pneumatosis Intestinalis: Do Not Excise These "Polyps"! PMID- 26157831 TI - Transnasal Endoscope Locked in a Bent Position Causing Difficult Withdrawal. AB - We report a rare but severe complication of routine transnasal esophagogastroduodenoscopy (EGD). The tip of a transnasal endoscope was locked in a bent position. Since the bent tip was unable to be returned to a neutral position, the snare from another endoscope inserted transorally was used to straighten it, which allowed the transnasal endoscope to be withdrawn with only mild injury to the gastric mucosa. Endoscopists should be aware of this complication and how to manage it. PMID- 26157830 TI - Enterocutaneous Fistula From A Billroth II Afferent Limb: Successful Closure With Endoclips. AB - Recently, indications for endoscopic clips have expanded to include closure of gastrointestinal fistulae and perforations. A 62-year-old man with remote history of surgery for peptic ulcer underwent right hemicolectomy for a large hepatic flexure mass with proximal colonic dilatation. During surgery, inadvertent pinpoint duodenotomy of the afferent Billroth II limb resulted in a duodeno cutaneous fistula. Despite total parental nutrition, cutaneous bile drainage persisted. The duodenal fistula was closed during upper endoscopy using three endoclips. Cutaneous bile drainage stopped, and the abdominal wall defect healed. This is the first published case of endoclip closure of an iatrogenic duodenal fistula from a Billroth II afferent limb. PMID- 26157832 TI - Severe Ulcerative Esophagitis Induced by Crizotinib Therapy. AB - Crizotinib is an oral tyrosine-kinase inhibitor that inhibits anaplastic lymphoma kinase (ALK) in gene-rearranged non-small cell lung cancer (NSCLC). In 2011, the Food and Drug Administration approved crizotinib for treatment of locally advanced or metastatic ALK-positive NSCLC. The crizotinib adverse events profile included esophageal disorders in 11% of patients treated during trial phases I, II, and III, but none of them had severe events. We describe the development of severe ulcerative esophagitis secondary to crizotinib therapy and the re introduction of therapy at a lower dose without recurrence of esophageal symptoms. PMID- 26157833 TI - Rapunzel Syndrome in a Postpartum Patient after Caesarian Delivery. AB - A trichobezoar is an immobile, indigestible collection of hair or hair-like fibers that accumulates within the GI tract. Rapunzel syndrome is a rare variant in which a trichobezoar extends into the small intestine, potentially causing obstruction. We describe the first case, to our knowledge, of Rapunzel syndrome occurring in a postpartum patient after delivery by Caesarian section. PMID- 26157834 TI - Nodular Lymphoid Hyperplasia in a Patient Initially Believed to Have Familial Adenomatous Polyposis. AB - A 50-year-old male was initially thought to have familial adenomatous polyposis (FAP) after innumerable small nodules in the upper GI tract were discovered upon endoscopic retrograde cholangiopancreatography for common bile duct stone extraction. ERCP was unsuccessful due to inability to find the major papilla amongst the nodules found in the duodenum. Biopsy of the nodules was consistent with nodular lymphoid hyperplasia. The patient was later found to have common variable immunodeficiency. PMID- 26157835 TI - Bannayan Ruvalcaba Riley Syndrome. AB - A 63-year-old male with history of prostate cancer treated with radiation presented for a colonoscopy for small volume hematochezia. The colonoscopy revealed numerous polyps, which were found to be ganglioneuromas on histological examination. He was referred to medical genetics with suspicion for hamartomatous polyposis syndrome and was found to have a mutation in the PTEN gene. Based on this and suggestive clinical findings, he was diagnosed with Bannayan Ruvalcaba Riley syndrome. PMID- 26157836 TI - A Rare Case of Nephrocolic Fistula Resulting from Radio Frequency Ablation (RFA) of Renal Cell Carcinoma. AB - Nephrocolic fistula is a rare, abnormal fistulous connection between the urinary system (kidney/ureters) and colon. Different benign and malignant etiologies are implicated in the formation of a nephrocolic fistula. Even though conservative treatment options have been tried recently (especially for benign etiologies), surgical resection has been the treatment of choice and should be pursued if conservative management fails. We report the first case of a nephrocolic fistula after a radiofrequency ablation of a renal cell carcinoma, which required surgical resection after conservative management failed. PMID- 26157837 TI - Synchronous Small Cell Neuroendocrine Carcinoma and Adenocarcinoma of the Colon: A Link for Common Stem Cell Origin? AB - Synchronous carcinomas have been recognized for over a century, with synchronous primary adenocarcinoma of the colon reported to range from 2-11% of cases involving this type of malignancy. Small cell carcinomas occur frequently with colorectal adenomas; however, despite these reports and a known adenoma-to carcinoma sequence, scarce literature exists on synchronous colorectal adenocarcinoma and small cell carcinomas. We present a rare cancer of synchronous small cell neuroendocrine carcinomas and discuss a possible link between these two cancers. PMID- 26157838 TI - Ischemic Colitis, the Great Imitator: A Mass Completely Resolved. AB - Ischemic colitis (IC) is the most common type of intestinal ischemia, with a vast clinical spectrum of injury ranging from mild and transient ischemia to acute fulminant colitis. The pattern of injury is usually segmental, but it is mainly dictated by individual anatomy, duration of ischemia, and degree of re-perfusion injury. Analysis of clinical presentation, early endoscopic evaluation, and biopsy are all essential for prevention of misdiagnosis. We present a unique case of IC with mass-like features on regular imaging, emphasizing the importance of endoscopy and biopsy for accurate diagnosis. PMID- 26157839 TI - Recurrent Acute Pancreatitis Secondary to Graft Pancreas Divisum in a Patient with Modified Multi-Visceral Transplant. AB - A patient with modified multivisceral transplant developed recurrent acute pancreatitis (RAP) 1 year after transplant and was found to have graft pancreas divisum with otherwise negative work-up for identifying the etiology of RAP. Endoscopic retrograde cholangiopancreatography was performed with minor papilla sphincterotomy and pancreatic duct stent placement of the graft pancreas. The patient's symptoms resolved following endotherapy for a follow-up period of 2 years. This is a unique case of graft pancreatitis secondary to pancreas divisum. PMID- 26157840 TI - Pancreatitis Secondary to Celiac Trunk Dissection. AB - Dissection of the visceral arteries happens infrequently, with the superior mesenteric artery being the most commonly affected. Isolated dissection of the celiac trunk is rare, and only a few cases have been reported in the medical literature. We report the case of a 51-year-old male who presented with abdominal pain and was subsequently diagnosed with a celiac trunk dissection with secondary pancreatitis and pancreatic infarction. The patient's symptoms improved with conservative medical management. We review the current literature involving celiac trunk dissection and its management, and provide discussion regarding this unrecognized complication of pancreatitis. PMID- 26157841 TI - Undifferentiated Carcinoma with Osteoclast-Like Giant Cells of the Pancreas in a Patient with New Diagnosis of Follicular Non-Hodgkin's Lymphoma. AB - Pancreatic tumors with osteoclast-like giant cells are rare, with only 50 cases published to date. We report a case of a 67-year-old male with a new diagnosis of follicular non-Hodgkin's lymphoma with an incidental pancreatic body mass on abdominal imaging. Cytology from the pancreatic mass obtained via endoscopic ultrasound-directed fine-needle aspiration (EUS-FNA) revealed an undifferentiated carcinoma with osteoclast-like giant cells. PMID- 26157842 TI - A Rare Case of Icteric Acute Hepatitis C Infection Acquired Through Intranasal Methamphetamine Use. AB - Most patients with acute hepatitis C (HCV) infections are asymptomatic, while 15% present with jaundice. Intranasal drug use can uncommonly transmit HCV via contaminated instruments and nasal epithelial breakdown. Given a 15% prevalence of HCV infection in chronic methamphetamine users, recognition of potential transmission routes is important to target prevention and screening efforts in this population. PMID- 26157843 TI - Sorafenib-Induced Grade Four Hepatotoxicity in a Patient with Recurrent Gastrointestinal Stromal Tumor (GIST): A Case Report and Review of Literature. AB - Gastrointestinal stromal tumor is a rare mesenchymal tumor. Sorafenib is an effective medication in these tumors based on two phase II clinical trials and a retrospective analysis. We report a rare case of a 57-year-old male with acute hepatotoxicity from sorafenib. He was treated conservatively with IV fluids and prednisolone. Liver function tests improved over 2 months. We conclude that sorafenib could cause life-threatening hepatotoxicity and patients taking sorafenib need to be closely monitored. PMID- 26157844 TI - Tips for a Successful Case Report. PMID- 26157845 TI - Unusual Finding of an Intact Moth During Routine Colonoscopy. PMID- 26157846 TI - Emphysematous Gastritis: An Ominous Diagnosis Managed Conservatively. PMID- 26157847 TI - Endosonographic Findings in Colitis Cystica Profunda. PMID- 26157848 TI - Hepatobiliary Fascioliasis: An Uncommon Cause of Biliary Obstruction in the United States. PMID- 26157849 TI - A Novel Approach to Management of Esophageal Pill Impaction. AB - A 26-year-old male presented with symptoms of acute esophageal obstruction immediately after swallowing an 800-mg ibuprofen tablet. Multiple attempts to extract the pill with a variety of traditional endoscopic retrieval devices were unsuccessful. We successfully destroyed the pill using a threaded-tip biliary stent retrieval device to drill a hole in the center of the pill, which allowed us to use a rat-tooth forceps to crush the pill. This case report demonstrates a novel use of this device in a challenging esophageal pill extraction. PMID- 26157850 TI - Hepatic Portal Venous Gas: An Unusual Complication Following Upper Endoscopy and Dilation. AB - Hepatic portal venous gas (HPVG), a rare condition in which gas accumulates in the portal venous circulation, is often associated with a significant underlying pathology, such as intestinal ischemia, sepsis, and trauma. HPVG after endoscopy or dilation is an unusual complication. We report a case of HPVG following upper endoscopy and dilation for an esophageal stricture in a 34-year-old patient with eosinophilic esophagitis (EoE). The patient was treated conservatively, and his symptoms resolved. Follow-up computed tomography (CT) scan showed resolution of HPVG. This case highlights a rare and potentially ominous complication of upper endoscopy and dilation and underscores the role of conservative management. PMID- 26157851 TI - Acute Esophageal Necrosis: A Case of Black Esophagus Associated with Bismuth Subsalicylate Ingestion. AB - We present a case of acute esophageal necrosis (AEN) likely caused by chronic use of bismuth subsalicylate, an active ingredient in over-the-counter Pepto Bismol((r)), which contains 220 g of salicylic acid in each 30 mL quantity. While aspirin is known to cause gastritis and gastric ulcers, this is the first case, to our knowledge, reporting AEN after chronic bismuth subsalicylate use. PMID- 26157852 TI - A Treatment Option for Esophageal Intramural Pseudodiverticulosis. AB - Esophageal intramural pseudodiverticulosis (EIPD) is a rare condition often presenting with esophageal strictures. Treatment is often limited to endoscopic dilatation and treatment of the underlying esophageal pathology. We present a case of a patient with longstanding GERD on famotidine (she experienced anaphylaxis with proton pump inhibitors [PPIs]) who presented with dysphagia and weight loss. Work-up revealed a diagnosis of EIPD with a 5-mm mid-esophageal stricture. Therapy with dilatation was unsuccessful until the addition of sucralfate, after which dilatation was successful and symptoms resolved. In patients who are unable to take PPIs, the addition of sucralfate may enhance the success of dilatations of esophageal strictures and EIPD. PMID- 26157853 TI - Glass Microparticulate Ingestion: An Unusual and Difficult-to-Diagnose Cause of Chronic Abdominal Pain. AB - In the absence of overt structural abnormalities, the diagnostic approach to chronic abdominal pain can be challenging. Occupational particulate inhalation causing injury to an organ other than the lung is rare. We report a case of inadvertent glass microparticulate ingestion causing chronic abdominal pain with altered local and systemic inflammatory responses. PMID- 26157854 TI - Hemophagocytic Lymphohistiocytic Syndrome and Enteropathy-Associated T-cell Lymphoma in a Patient with Refractory Celiac Disease. AB - A 70-year-old woman with celiac disease presented with weight loss and diarrhea unresponsive to gluten-free diet (GFD) and prednisone. Diagnosis of type 2 refractory celiac disease (RCD) was made by small intestinal biopsies showing severe villous blunting and intraepithelial lymphocytosis. She was diagnosed with hemophagocytic lymphohistiocytic syndrome (HLH) after developing fever, pancytopenia, hypofibrinogenemia, elevated ferritin, and demonstration of hemophagocytosis on her bone marrow biopsy. An expert pathologist on lymphoma reviewed her biopsies and revised the final diagnosis to type 1 enteropathy associated T-cell lymphoma (EATL) based on large T-cells infiltrating the lamina propria. We describe the first case of HLH associated with localized EATL and RCD. PMID- 26157855 TI - Asymptomatic Duodenal Perforation from an Inferior Vena Cava Filter. AB - Recent exponential increase in inferior vena cava (IVC) filter placements has led to a higher rate of filter complications. A 46-year-old man with a past history of IVC filter placement for bilateral deep vein thrombosis presented with lower abdominal pain. Imaging studies demonstrated IVC filter strut penetrations into multiple structures. Upper endoscopy confirmed an uncomplicated single IVC filter strut penetration into the duodenal wall. The abdominal pain was determined to be unrelated to IVC filter strut penetration, and the patient was managed conservatively. Although IVC filter strut penetrations can cause significant complications, current guidelines remain unclear for management of asymptomatic enteric IVC filter strut penetrations. PMID- 26157856 TI - Hematochezia Associated with Sevalamer-Induced Mucosal Injury. AB - We present a case of a 61-year-old woman with end-stage renal disease (ESRD) who developed painless hematochezia following initiation of anticoagulation. Work-up revealed a large ulceration in the sigmoid colon, and histologic images revealed sevelamer crystals embedded in the colonic mucosa, consistent with sevelamer crystal-mediated injury. This is a novel cause of gastrointestinal hemorrhage that has not previously been described in the literature. Physicians should be aware of the potential for sevelamer-induced injury. PMID- 26157857 TI - Use of Serum Infliximab Level Prior to Cyclosporine Salvage Therapy in Severe Ulcerative Colitis. AB - Medical treatment options for severe, steroid refractory ulcerative colitis (UC) include infliximab (IFX) or cyclosporine (CSA), but general consensus has been that both agents should not be used together or even successively. We report a case of a 17-year-old male with severe UC refractory to IV steroids with successful sequential salvage therapy guided by serum IFX level. After primary lack of response to IFX, an undetectable serum IFX level and elevated IFX antibodies were followed by immediate transition to IV CSA. This case demonstrates the possibility of therapeutic drug monitoring of IFX levels when calculating the risk/benefit ratio for patients with steroid-refractory UC failing primary salvage therapy. PMID- 26157858 TI - A Unique Case of Hematemesis in a 17-Year-Old Female. AB - Hemosuccus pancreaticus (HP) is a rare cause of gastrointestinal bleeding (GIB) that should be considered in a patient with a history of pancreatitis and GIB. A 17-year-old female presented with nausea followed by an episode of hematemesis. Fourteen weeks prior to presentation, she had 3 episodes of vomiting within a week. Six weeks prior to presentation, she developed abdominal pain and was diagnosed with acute idiopathic pancreatitis. Computed tomography (CT) revealed a cystic lesion arising in the gastroduodenal artery (GDA), and coil embolization was performed. There are no reported cases of HP in an adolescent with acute idiopathic pancreatitis. PMID- 26157859 TI - Groove Pancreatitis: Four Cases from a Single Center and Brief Review of the Literature. AB - Groove pancreatitis is a rare form of chronic pancreatitis that affects the groove anatomical area between the head of the pancreas, duodenum, and common bile duct. We provide a summary of the clinical findings of 4 groove pancreatitis cases diagnosed at a tertiary academic medical center over a 5-year period. A detailed review of the current literature surrounding this clinical entity is also provided. Although rare, groove pancreatitis should be considered in the differential diagnosis of patients presenting with pancreatic head mass lesions, as appropriate diagnosis can help avoid unnecessary surgical procedures. PMID- 26157860 TI - Bouveret's Syndrome with Severe Esophagitis and a Purulent Fistula. AB - Bouveret's syndrome is a rare variant of gallstone ileus with an overall incidence of 1-3%. It is a rare cause of gastric outlet obstruction resulting from the passage and impaction of a large gallstone through a cholecysto-duodenal fistula. A combination of diagnostic modalities is often required for a diagnosis. Management options include endoscopy and surgery. The most commonly performed procedures are enterolithotomy or gastrostomy, either alone or with cholecystectomy and fistula repair. We describe a unique variant of chronic Bouveret's syndrome with the unusual associations of severe esophagitis and a purulent fistula. PMID- 26157861 TI - A Case of an Ectopic Ampulla of Vater in the Pyloric Channel. AB - A 51-year-old male presented with abdominal pain and jaundice. He was subsequently diagnosed with cholestatic jaundice and cholangitis. A side-viewing duodenoscope failed to identify the ampulla of Vater in the second portion of duodenum. A regular gastroscope was used, and an ectopic ampulla of Vater was identified in the pyloric channel. PMID- 26157862 TI - Sarcoidosis Presenting as Necrotizing Sarcoid Granulomatosis of the Liver, Sclerosing Cholangitis, and Gastric Ulcer. AB - Sarcoidosis is a multisystem granulomatous disease. The liver is affected in up to 50-90% of cases. Sarcoidosis typically presents as non-necrotizing epithelioid granuloma. The occurrence of non-infective necrotizing sarcoid granuloma (NSG) is infrequent, and the finding of NSG in the liver is rare. We report a case of NSG of the liver and lymph nodes, granulomatous gastric ulcer, and secondary cholangitis coexisting in a patient. We discuss the clinical features of the case and briefly review NSG. There is only 1 previously reported case of NSG of the liver in literature. PMID- 26157863 TI - Polymyositis Associated with Hepatitis B Virus Cirrhosis and Advanced Hepatocellular Carcinoma. AB - Polymyositis (PM) is an inflammatory condition of skeletal muscle and is believed to be a paraneoplastic syndrome associated with various types of cancer. PM associated with chronic hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is very rare. We report a case of advanced HCC with chronic HBV cirrhosis that presented with proximal muscle weakness. Further investigation showed elevation of muscle enzymes, myopathic pattern of electromyography (EMG), and evidence of myositis compatible with PM. Lamivudine and 1 mg/kg of oral prednisolone were given. Two sessions of transcatheter arterial chemoembolization (TACE) were performed and sorafenib was started. Muscle enzymes normalized after 6 weeks of treatment. Unfortunately, 5 months after treatment, patient was readmitted and died of severe bacterial pneumonia. PMID- 26157864 TI - Ceftriaxone-Induced Gallstones: Case Report and Literature Review. AB - We report a case of gallbladder and common bile duct stones occurring in a 14 year-old male who was exposed to ceftriaxone for 6 weeks. Ceftriaxone-induced gallstones are under-reported and remain an important cause of gallstones in patients exposed to this antibiotic. Gallstone development should be considered in the appropriate clinical context. PMID- 26157865 TI - Looking Back, Moving Forward. PMID- 26157867 TI - Delayed Presentation of Splenic Rupture After Endoscopy in a Patient With Hemophilia A: Case Report and Review of the Literature. AB - An 88-year-old female presented with dyspnea on exertion and severe anemia. Colonoscopy was unremarkable and the patient was transfused with packed red blood cells prior to discharge. The patient returned 2 weeks later with severe abdominal pain, hypotension, and anemia. Computed tomography revealed splenic hematoma and hemoperitoneum. She bled from the surgical sites during emergent splenectomy and work-up revealed hemophilia A. We present, to our knowledge, a case of the longest reported delay in presentation of post-colonoscopy splenic rupture and the first in a patient with hemophilia A. PMID- 26157869 TI - Endoscopic Therapy of Bleeding from Radiation Enteritis with Hypertonic Glucose Spray. AB - Non-variceal and non-ulcerative bleeding in the gastrointestinal (GI) tract, such as radiation enteritis with active and extensive oozing, is common, and management of these conditions can be challenging. We describe the first case in the literature to use hypertonic glucose spray in radiation enteritis-associated diffuse mucosal bleeding. PMID- 26157871 TI - Autonomic Dysreflexia Resulting in Seizure After Colonoscopy in a Patient With Spinal Cord Injury. AB - There are many potential procedural risks associated with colonoscopy. We present a case of autonomic dysreflexia complicated by seizure after colonoscopy in a patient with a spinal cord injury. Autonomic dysreflexia is a disorder characterized by hypertension, bradycardia, headache, and diaphoresis and is associated with spinal cord injuries above the level of T6. Episodes can be precipitated by a variety of factors, including bladder distension and stool impaction. We suspect that colonic/rectal distension and rectal stimulation associated with the colonoscopy precipitated autonomic dysreflexia in our patient. PMID- 26157866 TI - White Ball Sign. PMID- 26157873 TI - Multifocal Synchronous Granular Cell Tumors of the Gastrointestinal Tract. AB - Granular cell tumors (GCT) are rare and unusual tumors, which are usually benign and asymptomatic. Only 5-10% of cases involve the gastrointestinal tract, most commonly as singular, non-cancerous lesions in the esophagus. We report a rare case of symptomatic, multifocal, synchronous GCT involving the esophagus, stomach, and cecum. PMID- 26157870 TI - Novel Use of Endoscopic Clips as Fiducials for Radiotherapy in Small Bowel Lymphoma. AB - A 31-year-old woman was diagnosed with duodenal grade 1 follicular lymphoma. The patient underwent radiotherapy and on surveillance enteroscopy, the lymphoma was persistently identified in the duodenum and jejunum. Endoscopic clips were used as fiducials to better localize the tumor during radiotherapy. Endoscopic clips are increasingly used as tumor localization tools because of their favorable risk benefit ratio. In our case, endoscopic clipping was necessary to properly localize the tumor after prior treatment failure, and the patient now has no evidence of disease. Larger studies are needed to demonstrate the efficacy of clips in tumor localization and improved disease-related morbidity. PMID- 26157868 TI - Vascular Injury Following Pyloric Dilation: Unusual Cause of Ischemic Colitis. AB - A 57-year-old female with intrahepatic cholangiocarcinoma underwent hepatic trisegmentectomy and chemoradiation. Her course was complicated by recurrent episodes of radiation-induced gastric outlet obstruction requiring balloon dilations. She presented with right lower quadrant pain after routine upper endoscopy with pyloric dilation. A computed tomography (CT) showed isolated right sided ischemic colitis with vascular contrast in the mesentery. Repeat CT after conservative management revealed near resolution of the ischemic changes. Perforation at the level of the pylorus is a complication of endoscopic pyloric dilation but vascular injury has never been described. PMID- 26157874 TI - Synchronous Gastric Metastasis of Renal Cell Carcinoma With Absence of Gastrointestinal Symptoms. AB - Renal cell carcinoma (RCC) is a rare adult malignancy, and one-third of cases present with distant metastases at the time of diagnosis. Early gastric metastasis is exceedingly rare. We describe an adult male with synchronous gastric metastasis of RCC at the time of diagnosis in the absence of gastrointestinal symptoms. We report the fifth case of RCC with synchronous gastric metastasis and the only case with early presentation in the absence of gastrointestinal symptoms. PMID- 26157872 TI - Transjugular Intrahepatic Portosystemic Shunt Prior to Endoscopic Mucosal Resection for Barrett's Esophagus in the Setting of Varices. AB - Patients with Barrett's esophagus (BE) and cirrhosis who develop high-grade dysplasia (HGD) or adenocarcinoma in the setting of esophageal varices present a unique therapeutic dilemma. There is limited literature regarding the optimal management of varices prior to invasive procedures or surgery involving the distal esophagus. We present a case of variceal decompression with a transjugular intrahepatic portosystemic shunt (TIPS) allowing for successful endoscopic mucosal resection (EMR) of BE with HGD overlying esophageal varices. PMID- 26157875 TI - Metastatic Gastric Adenocarcinoma in Cirrhosis. AB - We report the case of a woman with a new diagnosis of gastric adenocarcinoma that was found to have multifocal hepatic metastasis on routine diagnostic transjugular liver biopsy. The finding of metastatic disease in a background of cirrhosis is an unexpected finding that has negative treatment implications regarding use of cytotoxic chemotheraputic agents. PMID- 26157876 TI - Vibrio parahaemolyticus: A Rare Cause of Chronic Diarrhea in a Heart Transplant Patient. AB - Vibrio parahaemolyticus usually causes a self-limiting acute diarrheal illness, and is rarely tested for in cases of chronic diarrhea. We present a rare case of chronic diarrhea caused by V. parahaemolyticus in a heart transplant patient requiring antibiotic treatment. PMID- 26157877 TI - Mallory-Weiss Tear in the Duodenum. AB - Mallory-Weiss tears are mucosal lacerations caused by forceful retching and are typically located at the gastroesophageal junction. Mallory-Weiss tears have not been described in the duodenum. We report of a Mallory-Weiss tear in the descending duodenum of a 57-year-old man who presented with hematemesis preceded by forceful retching. We discuss the pathophysiology of a duodenal injury in comparison to typical tears occurring at the gastroesophageal junction. PMID- 26157878 TI - Uncovered Self-Expanding Metal Stent (SEMS) Four Years After Placement for Long Term Treatment of a Benign Colonic Obstruction. AB - Self-expanding metal stents (SEMS) have emerged as an alternative to surgery in the treatment of malignant colorectal obstructions. There is limited data about their use for benign colonic obstructions, especially in regards to safety and long-term patency. We present a case in which long-term SEMS placement proved to be a durable option for over 4 years in a patient with a benign colonic stricture. PMID- 26157879 TI - Intramural Duodenal Hematoma with Acute Pancreatitis in a Patient With an Overt Pancreatic Malignancy. AB - Intramural hematomas have rarely been associated with pancreatitis, and to date there is only 1 case report of an intramural hematoma occurring with pancreatic adenocarcinoma. We describe a patient who presented with gastric outlet obstruction secondary to a spontaneous intramural duodenal hematoma and was found to have a pancreatic adenocarcinoma on endoscopic ultrasound (EUS) after it was not visualized by computed tomography (CT). PMID- 26157880 TI - Acute Liver Failure Following One Year of Daily Consumption of a Sugar-Free Energy Drink. AB - We report a 36-year-old man who presented with 1 week of right upper quadrant abdominal pain, jaundice, and fatigue. He consumed 3 sugar-free energy drinks daily for the past year with binge alcohol use. His liver function progressively deteriorated, requiring orthotopic liver transplantation. Submassive hepatic necrosis with eosinophilic infiltrate was seen on pathology, consistent with drug induced liver injury. Further investigation is warranted into identifying which individuals are susceptible to liver failure from energy drink consumption. PMID- 26157881 TI - Parastomal Variceal Bleeding Attributed to Obstructive Pathology Successfully Treated by Percutaneous Variceal Embolization. AB - Parastomal variceal bleeding is a rare cause of gastrointestinal bleeding, but it should be considered as a potential etiology in patients with portal hypertension and surgical stomas. Though standard endovascular management has not yet been established, transjugular intrahepatic portosystemic shunt (TIPS) is a recommended treatment option leading to decompression of underlying portal hypertension. We present a case of parastomal bleeding treated with percutaneous parastomal variceal embolization, which is an emerging alternative therapy when TIPS cannot be performed. PMID- 26157882 TI - SlimQuickTM-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation. AB - Green tea extract is a popular ingredient in herbal weight loss supplements. There have been reports of hepatotoxicity associated with the use of dietary supplements, some of these cases lead to fatal outcomes. To our knowledge, we report the first case of fulminant hepatic failure requiring orthotopic liver transplantation caused by SlimQuickTM (Wellnx Life Sciences, Wilmington, DE), a widely available weight loss supplement containing green tea extract. PMID- 26157884 TI - Tips for Performing High-Quality Peer Reviews. PMID- 26157883 TI - Omental Infarction: An Unusual Cause of Left-Sided Abdominal Pain. AB - Left-sided omental infarction (OI) is rare in both the adult and pediatric patients. To our knowledge, only 2 pediatric cases of a left-sided OI have been reported in the literature. We report a case of an obese 13-year-old male who presented with a 6-day history of intermittent, colicky, left upper quadrant abdominal pain. PMID- 26157885 TI - Incidental Plasmacytoma in a Patient With Pathologic Fractures. PMID- 26157886 TI - Chicken Bone Impaction Diagnosed by Computer Tomography Angiography: A Rare Cause of Lower Gastrointestinal Bleeding. PMID- 26157887 TI - The Third Esophageal Sphincter: A Case of Dysphagia Lusoria. PMID- 26157888 TI - Gastric Heterotopic Pancreas Presenting as a Submucosal Tumor in a 27-Year-Old Male. PMID- 26157889 TI - Hydralazine-Induced Vasculitis With Gastrointestinal Pseudomelanosis. PMID- 26157890 TI - Adult Duodenal Pleomorphic Rhabdomyosarcoma. PMID- 26157891 TI - Umbilical Varix in a Cirrhotic Patient. PMID- 26157892 TI - Symptomatic Presentation of Intrahepatic Portal Vein Aneurysm. PMID- 26157893 TI - Hereditary Hemorrhagic Telangiectasia With Liver Vascular Malformation Presenting With High-Output Heart Failure. PMID- 26157894 TI - Closure of a Chronic, Non-Healing Tracheoesophageal Fistula With a New Over-the Scope Clip. AB - Tracheoesophageal fistulas can arise from both benign and malignant conditions, and often present clinically as increased secretions, coughing with or without hypoxia after swallowing, and recurrent aspiration pneumonia. We describe a tracheoesophageal fistula in a post-chemotherapy lymphoma patient that was closed with use of an over-the-scope Aponos clip. PMID- 26157895 TI - Splenic Avulsion Following PEG Tube Placement: A Rare but Serious Complication. AB - Placement of a percutaneous endoscopic gastrostomy (PEG) tube is a common procedure to allow for enteral nutrition in patients with multiple indications. PEG tube placement is a safe procedure with minor complications such as site infection and irritation. One of the more severe complications is splenic laceration, which may result in intra-peritoneal bleeding and manifest as an acute abdomen. We present a rare case of intra-abdominal bleeding secondary to catastrophic splenic injury 12 hours after PEG tube placement resulting in hemodynamic compromise. The patient underwent splenectomy and had an uneventful recovery. PMID- 26157896 TI - Eltrombopag Use in Thrombocytopenia for Endoscopic Submucosal Dissection of a Gastric Carcinoid. AB - Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain platelet levels for the safe and complete endoscopic submucosal dissection of a gastric carcinoid in a patient with severe thrombocytopenia due to cirrhosis and idiopathic thrombocytopenic purpura. We performed complete and safe endoscopic removal of a gastric carcinoid after correcting the thrombocytopenia. PMID- 26157897 TI - Acute Mesenteric Ischemia Caused by Rare Cardiac Tumor Embolus. AB - Acute mesenteric ischemia (AMI) is a rare vascular emergency associated with a high mortality rate. The most common cause of AMI is cardiac emboli from thrombi associated with atrial fibrillation or following myocardial infarction. We present a case of AMI caused by a unique source of emboli, confirmed as an embolization of a cardiac sarcoma to the small bowel by matching biopsies obtained from the superior mesenteric artery (SMA) and the embolic source. PMID- 26157898 TI - An Unusual Case of Obstruction Due to Colonic Intussusception in a Scleroderma Patient. AB - Scleroderma is an autoimmune disease that can affect multiple organ systems, including the gastrointestinal tract. Intussusception, the telescoping of the bowel that can lead to intestinal obstruction, is an uncommon phenomenon in adults. We report the first case of sigmoid intussusception in a patient with scleroderma. PMID- 26157899 TI - Tacrolimus Therapy for Ulcerative Colitis-Associated Post-Colectomy Enteritis. AB - Ulcerative colitis (UC)-associated pan-enteritis is a newly identified clinical entity that occurs almost exclusively after colectomy. Characterized by diffuse small bowel mucosal inflammation not compatible with Crohn's disease, the optimal treatment modality for this condition is unknown. Tacrolimus is a potent calcineurin inhibitor that has been successfully used in the treatment of UC. We describe a case of severe refractory pan-enteritis after colectomy for UC that was successfully treated with oral tacrolimus after failing intravenous corticosteroid treatment. Tacrolimus may be a safe and effective treatment modality for diffuse enteritis after colectomy in UC patients. PMID- 26157900 TI - Endoscopic Retrograde Cholangiopancreatography as a Risk Factor for Pancreatic Panniculitis in a Post-Liver Transplant Patient. AB - Post endoscopic retrograde cholangiopancreatography (ERCP) pancreatic panniculitis is a rare condition caused by fat necrosis following release of pancreatic enzymes into the bloodstream. No previous reports of pancreatic panniculitis have been reported in post-liver transplant subjects undergoing ERCP. We present a 63-year-old cryptogenic cirrhotic female post-cadaveric liver transplant who underwent ERCP for suspected biliary stricture and subsequently developed pancreatic panniculitis. PMID- 26157901 TI - Treatment of Leptomeningeal Carcinomatosis in a Patient With Metastatic Cholangiocarcinoma. AB - A 49-year-old woman with cholangiocarcinoma metastatic to the lungs presented with new-onset unrelenting headaches. A lumbar puncture revealed malignant cells consistent with leptomeningeal metastasis from her cholangiocarcinoma. Magnetic resonance imaging (MRI) of the brain revealed leptomeningeal enhancement. An intrathecal (IT) catheter was placed and IT chemotherapy was initiated with methotrexate. Her case is notable for the rarity of cholangiocarcinoma spread to the leptomeninges, the use of IT chemotherapy with cytologic and potentially symptomatic response, and a possible survival benefit in comparison to previously reported cases of leptomeningeal carcinomatosis secondary to cholangiocarcinoma. PMID- 26157902 TI - A New-Onset Rash in the Setting of Rifaximin Treatment for Hepatic Encephalopathy. AB - We present one of the first cases in the literature to describe an association between Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and rifaximin treatment in a patient with a recent diagnosis of alcoholic hepatitis, stage 2 hepatic encephalopathy, and no known existing allergies. Although SJS/TEN may be a rare reaction with rifaximin, it should be an important clinical consideration. PMID- 26157903 TI - Osteopetrosis: A New Cause of Upper Gastrointestinal Bleeding. AB - Osteopetrosis is a genetic disorder of bone remodeling caused by osteoclast dysfunction. Clinical features include short stature, frequent fractures, and recurrent infections. Abnormal bone obliterates the marrow cavity, resulting pancytopenia and extramedullary hematopoiesis in the liver and spleen. The splenomegaly can lead to left-sided portal hypertension. We report the second case of osteopetrosis-induced portal hypertension and the first case of upper gastrointestinal bleeding in a 52-year-old woman with osteopetrosis. PMID- 26157904 TI - Aspirin-Induced Acute Liver Injury. AB - Aspirin is thought to be a relatively safe drug in adults. The association of aspirin and Reye syndrome in children is well documented. We report a 41-year-old female with pericarditis who was treated with high-dose aspirin and developed subsequent acute liver injury. After discontinuation of aspirin, liver enzyme elevation and right upper quadrant pain both resolved. We conclude that high-dose aspirin should be considered as a potentially hepatotoxic agent. PMID- 26157905 TI - Refractory Hypoglycemia Presenting as First Manifestation of Advanced Hepatocellular Carcinoma. AB - Hypoglycemia is a well-established paraneoplastic manifestation of hepatocellular carcinoma (HCC). However, hypoglycemia presenting as the primary presentation of HCC is extremely rare. Most cases are resistant to glucose infusion and may lead to severe complications such as hypoglycemic seizures. We present a patient who had hypoglycemia as first manifestation of HCC and was managed conservatively. PMID- 26157906 TI - Pseudo-Ludwig's Phenomenon: A Rare Clinical Manifestation in Liver Cirrhosis. AB - Pseudo-Ludwig's phenomenon, an exceedingly rare clinical entity, is characterized by non-infectious upper airway obstruction resulting from spontaneous hematoma in the sublingual space. The condition is often described in patients on anticoagulants with grossly deranged coagulation profile. We describe a case of pseudo-Ludwig's phenomenon in a cirrhotic patient with significantly deranged hemostasis profile; the first to be reported in medical literature. PMID- 26157907 TI - Graft-Versus-Host Disease of the Upper Gastrointestinal Tract After an Autologous Stem Cell Transplant. AB - Graft-versus-host disease (GVHD) in recipients of autologous stem cell transplantation (SCT) is less common compared to recipients of allogeneic SCT, but its existence has been well documented. Similarly, the diarrheal component of the disease is highlighted when discussing its gastrointestinal (GI) manifestations, with less emphasis given to upper GI symptoms like nausea and vomiting. We present a case illustrating the upper GI tract signs and symptoms of GVHD after autologous SCT, and emphasize that prompt treatment can rapidly improve morbidity and prevent disease progression. PMID- 26157908 TI - Neonatal Cholestasis Caused by Undiagnosed Maternal Graves' Disease. AB - Neonatal cholestasis results from a variety of etiologies, including anatomic, infectious, and metabolic abnormalities. Hyperthyroidism, in contrast to hypothyroidism, is infrequently associated with neonatal cholestasis. Newborn screening is an important tool to detect newborn metabolic disorders, including thyroid dysfunction. However, one must exercise caution when interpreting these reports; typically only high thyroid stimulating hormone (TSH) levels are flagged as abnormal, while low or undetectable levels may not be. We present a unique case of cholestasis in a hyperthyroid neonate of an untreated, undiagnosed mother with Graves' disease; the infant's metabolic screen was not flagged as abnormal. PMID- 26157909 TI - Successful Use of Esophageal Stent Placement to Treat a Postoperative Esophageal Stricture in a Toddler. AB - Esophageal atresia (EA) is the most common type of gastrointestinal atresia. The most common variant (type C) consists of a blind esophageal pouch with a fistula between the trachea and the distal esophagus. Surgical repair can be complicated by the development of benign stricture. Most strictures are amenable to dilation, but refractory strictures may require surgical intervention. A 24-month-old boy born with tracheoesophageal fistula and EA underwent surgical repair on day 1 of life. He developed esophageal stricture that responded to esophageal stent placement. Endoscopic biliary accessories can be safely used to dilate refractory esophageal strictures in children, and should be considered prior to seeking other complex alternatives. PMID- 26157910 TI - Improve Your Case Reports With Videos and Images. PMID- 26157911 TI - Post-Endoscopy Sialadenitis. PMID- 26157912 TI - Desiccant-Induced Esophageal Obstruction: An Emerging Patient Safety Issue. PMID- 26157913 TI - Diagnosis and Management of an Esophagogastric Fistula as a Rare Complication of Nissen Fundoplication. PMID- 26157914 TI - MALT Lymphoma Causing Gastric Outlet Obstruction. PMID- 26157915 TI - Pseudomelanosis Duodeni. PMID- 26157916 TI - Pyogenic Granuloma of the Descending Colon: A Rare Cause of Lower Gastrointestinal Bleeding. PMID- 26157917 TI - A Rare Case of Dual Cecae. PMID- 26157918 TI - Starry Liver: An Unexpected Diagnosis. PMID- 26157919 TI - Telaprevir-Induced DRESS Syndrome Associated With Salmonella typhi. PMID- 26157920 TI - Endoscopic Band Ligation For Treatment of a Colonic Polyp Extending Into the Colonic Diverticulum. AB - A 66-year-old male was referred for the treatment of a polyp extending into a diverticulum. Endoscopic band ligation (EBL) was used to resolve the diverticulum. The banded diverticulum resolved and scar formation was observed 2 months after EBL. Residual small polypoid lesions were resected using endoscopic mucosal resection (EMR), and no complications occurred after treatment. PMID- 26157921 TI - Caustic Injury and Stricture of the Esophagus After Long-Term Phenytoin Use. AB - A 50-year-old man with a history of epilepsy controlled with phenytoin presented for evaluation of dysphagia. History revealed the patient was taking his phenytoin daily without water. Barium esophagram showed severe stricturing of the mid-esophagus. Upper endoscopy revealed diffuse gross mucosal abnormality with a thick stricture and occasional exudate. Biopsies were consistent with a drug induced injury with lymphocytic infiltration and epithelial cell necrosis. PMID- 26157922 TI - Gastric Duplication Cyst With Elevated Amylase: An Unusual Presentation Mimicking Pancreatic Cystic Neoplasm. AB - Enteric duplication cysts (EDCs) are benign congenital anomalies that are found incidentally in adults. Gastric duplication cysts (GDCs) are the least common subtype of EDC, but when located near the pancreas, may resemble other neoplastic conditions. We report a case of GDC adjacent to the pancreas with high cystic fluid amylase and carcinoembryonic antigen (CEA) and 3 different epithelia (respiratory, gastric, and intestinal), all diagnosed via endoscopic ultrasound with fine-needle aspiration. PMID- 26157923 TI - Gastric Polyposis: A Rare Cause of Iron Deficiency Anemia in a Patient With Portal Hypertension. AB - Portal hypertension leading to gastric polyposis has rarely been reported. More common gastric manifestations of portal hypertension are portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE). We report a case of a patient in whom portal hypertension manifested as bleeding gastric polyps leading to transfusion-dependent iron deficiency anemia. PMID- 26157924 TI - A Case of Severe Sprue-Like Enteropathy Associated With Valsartan. AB - Olmesartan sprue-like enteropathy is an adverse drug reaction that mimics the appearance of celiac disease and is related to the use of olmesartan. We present the case of a 71-year-old female with severe enteropathy attributed to celiac disease for 5 years that improved only after valsartan cessation. This is the first case associating valsartan with sprue-like enteropathy. PMID- 26157925 TI - Celiac Crisis in a 64-Year-Old Woman: An Unusual Cause of Severe Diarrhea, Acidosis, and Malabsorption. AB - Celiac disease (CD) rarely presents with life-threatening complications in older individuals. We report a 64-year-old woman who presented with profuse diarrhea, weight loss, hemodynamic instability, hypokalemia, hypoproteinemia, acidosis, and vitamin and iron deficiency. Pathologic and serologic studies confirmed CD presenting with celiac crisis with extensive and severe intestinal disease. Although celiac crisis occurs mostly in childhood and early adulthood, it should be considered in adults presenting with acute severe diarrheal illness, electrolyte abnormalities, and malabsorption. PMID- 26157926 TI - Splenic Pseudoaneursym as the Cause of Recurrent Gastrointestinal Bleeding in a Woman With Diffuse Scleroderma. AB - A 67-year-old woman with a 15-year history of intestinal scleroderma presented with recurrent melena. Upper endoscopies revealed a healing, non-bleeding, large gastric ulcer. After the third bleed, angiography demonstrated bleeding from a splenic artery pseudoaneurysm adjacent to the gastric ulcer. Scleroderma patients are at risk of bleeding from esophagitis or gastric arteriovenous malformations, while splenic artery pseudoaneurysms are primarily attributed to pancreatitis and trauma. This is the first reported case of gastrointestinal bleeding from a splenic artery pseudoaneurysm in a patient with intestinal scleroderma and a large gastric ulcer. PMID- 26157927 TI - Biliary Obstruction After Transjugular Intrahepatic Portosystemic Shunt Placement in a Patient With Budd-Chiari Syndrome. AB - A 20-year-old male presented with 2 months of progressive abdominal distension due to ascites and Budd-Chiari syndrome. He underwent transjugular intrahepatic portosystemic shunt (TIPS) placement, but soon after had elevated liver enzymes. MRCP revealed mild left intrahepatic biliary dilatation without stones or obvious stricture. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a focal stricture due to compression by the TIPS. The stricture was dilated and a 10 Fr x 15-cm plastic stent was placed with excellent biliary drainage. The patient's symptoms and liver tests normalized within 1 week. This is the first case of biliary obstruction due to TIPS placement effectively managed by ERCP. PMID- 26157928 TI - Taking an Alternate Route Home: Stenting of Choledochoduodenal Fistula. AB - A 53-year-old male with adenocarcinoma of the rectum with metastasis to liver and porta hepatis region underwent biliary stenting due to aggressive distal common bile duct stricture. At the time of planned stent exchange, the guidewire could not be re-introduced, despite several techniques, including the SpyScope((r)) system. A small fistula was noted by contrast fluoroscopy extending between proximal biliary tree/porta hepatis and the duodenal bulb, likely secondary to previous chemotherapy and radiation. A stent was placed in this fistula, as this was the only pathway available for biliary drainage. PMID- 26157929 TI - Primary Amyloidosis Presenting as Common Bile Duct Obstruction With Cholangitis. AB - A 61-year-old woman presented with features of acute cholangitis and distal common bile duct obstruction. Histopathology from ampulla of Vater biopsy demonstrated extensive local amyloid deposition. Amyloidomas can cause local obstructive effects and have been described in the small intestine, stomach, and gallbladder. This is the second case of a discrete amyloid deposit causing extrahepatic biliary obstruction and cholangitis. PMID- 26157930 TI - Acalculous Cholecystitis as the Initial Presentation of Systemic Diffuse Large B Cell Lymphoma. AB - The involvement of the gallbladder in systemic lymphoma is extremely rare. We report a challenging case of systemic diffuse large B-cell lymphoma (DLBCL) that initially presented with septic shock from acalculous cholecystitis. After extensive investigation, DLBCL was found to be the underlying cause of gallbladder disease. PMID- 26157931 TI - Subhepatic Sterile Abscess 10 Years After Laparoscopic Cholecystectomy. AB - We present a case of a large, sterile, subhepatic abdominal wall abscess secondary to foreign body reaction to dropped gallstones during laparoscopic cholecystectomy performed 10 years ago. Dropped gallstones are common complications of laparoscopic cholecystectomy, but they rarely result in abscess formation. When abscesses do occur, they may present a few months to a few years after surgery. It is important to recognize dropped gallstones as an etiology for subhepatic abscess in patients with history of laparoscopic cholecystectomy. PMID- 26157932 TI - Amiodarone-Induced Liver Injury and Cirrhosis. AB - We present a case report of an 80-year-old woman with volume overload thought initially to be secondary to heart failure, but determined to be amiodarone induced acute and chronic liver injury leading to submassive necrosis and bridging fibrosis consistent with early cirrhosis. Her histopathology was uniquely absent of steatosis and phospholipidosis, which are commonly seen in AIC. PMID- 26157933 TI - A Case of Non-Cirrhotic Portal Hypertension Associated With Chronic Didanosine Therapy. AB - A 66-year-old man with HIV and recurrent thromboembolism presented with new-onset ascites with an extensive diagnostic work-up that was unremarkable. He was diagnosed with non-cirrhotic portal hypertension after a liver biopsy revealed mild fibrosis and hepatic venography revealed an elevated hepatic venous pressure gradient. The etiology of portal hypertension was attributed to didanosine therapy, a rare but noted side effect. PMID- 26157934 TI - Remission of Refractory Celiac Disease With Infliximab in a Pediatric Patient. AB - Refractory celiac disease (RCD) is a rare but life-threatening complication of celiac disease (CD), and only 1 pediatric case has been reported. We report a case of a 14-year-old girl with CD presenting with persistent symptoms and positive tissue celiac-specific antibodies despite a gluten-free diet. Push enteroscopy showed jejunal scalloping and partial villous atrophy on histology. She was diagnosed with RCD and treated with infliximab with subsequent complete serological and histological remission. PMID- 26157935 TI - How to Take Advantage of Mentorship. PMID- 26157936 TI - Portal Hypertensive Polyposis: A Consequence of Esophageal Variceal Ligation? PMID- 26157937 TI - Idiopathic Esophageal Ulcers in AIDS Completely Healed With Highly Active Anti Retroviral Therapy. PMID- 26157938 TI - Novel Endoscopic Finding Associated With Gastrointestinal Hemorrhage in a Post Stem Cell Transplant Patient With Light Chain Amyloidosis. PMID- 26157939 TI - Metastatic Choriocarcinoma of the Small Intestine Presenting as Refractory Anemia and Melena. PMID- 26157940 TI - A Patient With Gardner's Syndrome and Familial Adenomatous Polyposis Presenting With Extra-abdominal Desmoid Tumors and Diffuse Intestinal Polyposis. PMID- 26157941 TI - Colonic Lipoma With Gastrointestinal Bleeding and Intussusception. PMID- 26157942 TI - Malignant Coloduodenal Fistula: An Unusual Cause of Vomiting. PMID- 26157943 TI - Argon Plasma Coagulation for Extraction of an Impacted Trapezoid Basket in the Pancreatic Duct. AB - We performed endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy for pancreatic stent placement on a 55-year-old woman with a dilated pancreatic duct, pancreatic duct stone, and chronic pancreatitis. During follow-up ERCP, the lithotripter traction wire fractured during electrohydraulic lithotripsy and mechanical lithotripsy. Multiple attempts using standard techniques to clear the lithotripter and stone failed. Argon plasma coagulation (APC) was used to ablate 2 of the lithotripter wires, and the lithotripter was disengaged from the stone and removed. PMID- 26157944 TI - Pylephlebitis After Colonic Polypectomy Causing Fever and Abdominal Pain. AB - Pylephlebitis is a rare condition with a high mortality risk if not recognized and treated early. The most common symptoms include fever and abdominal pain, with the majority of cases manifesting with a polymicrobial bacteremia. We report an elderly woman with pylephlebitis presenting with fever, abdominal pain, diarrhea, and vomiting, likely secondary to a polypectomy 6 weeks prior. Abdominal CT revealed portal vein thrombus and blood cultures grew Streptococcus milleri and Haemophilus parainfluenza type V. Pylephlebitis should be considered when symptoms and signs of infection develop following endoscopic procedures, particularly in patients with an underlying hypercoaguable disease. PMID- 26157945 TI - Safety and Efficacy of Endoscopic Submucosal Dissection for Non-Ampullary Duodenal Neoplasms: A Case Series. AB - Sixteen non-ampullary duodenal neoplasms in 16 patients were treated with endoscopic submucosal dissection (ESD) performed by an endoscopist and an instrument assistant between February 2011 and November 2014. En bloc resection was performed in 15 cases (94%); lateral and vertical margins were pathologically free in 13 cases. Perforation occurred during submucosal dissection using a flex knife, but no perforations occurred in 15 cases using the hook knife only. No postoperative bleeding nor recurrence has been reported in any patient during the median 17-month follow-up period. Use of the hook knife as the main instrument and targeted training of the endoscopist and instrument assistant contributed to safe and effective duodenal ESD for non-ampullary duodenal neoplasms. PMID- 26157946 TI - Persistent Singultus: Addressing Complexity With Simplicity. AB - The hiccup reflex arc involving the brainstem, phrenic and vagus nerves, and the sympathetic chain is associated with singultus. There are many possible organic, psychogenic, idiopathic, and iatrogenic instigators. We describe a case of singultus in a 69-year-old man secondary to his CPAP mask, with resolution after he stopped using the mask. Our case establishes that CPAP may be a cause of iatrogenic aerophagia leading to gastric distention, singultus, and emesis and highlights the importance of a complete history. PMID- 26157947 TI - Alpha Fetoprotein-Secreting Gastric Cancer in the Setting of Chronic Hepatitis B: The Role of Endoscopy. AB - Alpha-fetoprotein (AFP) is a common tumor marker for hepatocellular carcinoma (HCC). We report a unique case of an AFP-producing gastric cancer in an elderly man with known chronic hepatitis B (HBV) and a markedly elevated AFP. Thorough diagnostic imaging failed to reveal a HCC, but a gastric adenocarcinoma was found on endoscopy. After successful resection, the serum AFP normalized. On histopathologic examination, the cancer demonstrated focal positive staining for AFP, in keeping with a hepatoid gastric adenocarcinoma. Endoscopy should be considered in clinical situations where increased serum AFP is detected but no HCC is found. PMID- 26157948 TI - Upper Gastrointestinal Bleeding as a Manifestation of Metastasis from Laryngeal Cancer. AB - Upper gastrointestinal (GI) bleeding can be a rare manifestation of primary or metastatic tumor in the stomach. Tumors that commonly metastasize to stomach include breast, lung, and malignant melanoma. Laryngeal cancer usually metastasizes to the lung and cervical spine. We report the first case of upper GI bleed as a manifestation of laryngeal cancer in the stomach. PMID- 26157949 TI - Giant Cystic Arteriovenous Malformation of the Mesentery and the Role of Cross Sectional Imaging in Occult Gastrointestinal Bleeding. AB - A 29-year-old woman presented with profound iron-deficiency anemia. Cross sectional imaging identified a mass in the ileal mesentery. Surgical resection was curative and revealed a giant cystic arteriovenous malformation. Our report highlights the role of cross-sectional imaging in the evaluation and management of iron-deficiency anemia and obscure gastrointestinal hemorrhage. PMID- 26157950 TI - Basaloid Squamous Cell Carcinoma of the Sigmoid Colon. AB - Basaloid squamous cell carcinoma (BSCC) of the colon is rarely found proximal to the anal canal. We report a case of an 81-year-old woman who was diagnosed with squamous cell carcinoma (SCC) of the lung without metastasis and BSCC of the sigmoid with differing histologic findings suggesting that these tumors were separate primary neoplasms. SCC of the colon has a dismal prognosis. Surgery is the primary method of treatment when feasible, in addition to chemotherapeutic agents. PMID- 26157951 TI - Cytomegalovirus Colitis Mimicking Rectal Carcinoma in a Young Immunocompetent Patient. AB - Cytomegalovirus (CMV) infection is often seen in immunocompromised patients. Rarely, immunocompetent patients may present with CMV as a self-limiting, flu like illness, though a few cases of significant organ-specific complications have been reported in these patients. We report a case in which a previously healthy man presented with hematochezia and an obstructing rectal mass thought to be rectal adenocarcinoma. Biopsy was positive for CMV, which was treated with full resolution of rectal mass confirmed with colonoscopy and barium contrast enema. This is the first reported case of CMV colitis mimicking rectal adenocarcinoma in an immunocompetent patient. PMID- 26157952 TI - Colonic Varices Due to Chronic Pancreatitis: A Rare Cause of Lower Gastrointestinal Bleeding. AB - A 75-year-old man with chronic pancreatitis presented with painless bloody stool. Computed tomography revealed a splenic vein occlusion with several collaterals towards the descending colon. Colonoscopy showed tortuous varices in the descending colon, which suggested recent bleeding. Sinistral portal hypertension (SPH) due to chronic pancreatitis was diagnosed, so splenectomy and distal pancreatectomy were performed. Our case illustrates a rare complication of SPH. PMID- 26157953 TI - Crohn's Disease Causes a Catastrophe. AB - Patients with Crohn's disease are at higher risk of developing antiphospholipid antibody syndrome (APS), of which 1% develop life-threatening, rapidly progressive clotting known as catastrophic APS (CAPS). A 17-year-old male presented with intermittent bloody diarrhea and abdominal pain. He developed myopericarditis, alveolar hemorrhage, left frontal and parieto-occipital infarct, superior sagittal sinus venous thrombosis, disseminated intravascular coagulation, and a pulmonary embolus. He was treated with high-dose pulse steroids, anticoagulation, and plasma exchange. Colonoscopy revealed a flare of Crohn's disease, and azathioprine was initiated. PMID- 26157954 TI - Anakinra Hepatotoxicity in a Patient With Adult-Onset Still's Disease. AB - We report a 46-year-old white woman with adult-onset Still's disease (AOSD) treated with anakinra, a IL-1B receptor antagonist. Within weeks, her liver enzymes deteriorated; subsequent cessation and rechallenge confirmed anakinra related drug-induced liver injury (DILI). Although AOSD has been associated with liver involvement, little is known about the hepatotoxicity of anakinra. Heightened awareness by gastroenterologists and hepatologists is warranted. PMID- 26157955 TI - Constrictive Pericarditis as a Cause of Refractory Ascites. AB - We report a 43-year-old man who presented for evaluation of ascites, varices, and hepatosplenomegaly. Initial labs were notable for normal platelets, mild liver synthetic dysfunction, and disproportionately elevated alkaline phosphatase. He was presumed to have underlying cirrhosis, and diuresis was attempted without success. A transjugular liver biopsy showed marked sinusoidal dilation without cirrhosis. Diagnostic paracentesis revealed fluid studies suggestive of cardiac ascites. Further cardiac evaluation confirmed constrictive pericarditis. The case highlights the importance of considering a broad differential in the evaluation of ascites. PMID- 26157956 TI - Drug-Induced Liver Injury After Soy Protein Supplement Use. AB - Drug-induced liver injury (DILI) is an important and often elusive cause of iatrogenic hepatic injury which complicates its recognition and treatment. We describe a rare case of severe liver injury in a previously healthy individual associated with a commonly used and reportedly safe soy protein powder supplement. Discontinuation of the supplements and initiation of ursodeoxycholic acid provided symptomatic relief, decreased pruritus, and resulted in a resolution of hepatic panel labs. PMID- 26157957 TI - Acute Liver Failure Due to Budd-Chiari Syndrome in the Setting of Cardiac Synovial Sarcoma. AB - Primary malignant tumors of the heart, specifically cardiac sarcomas, are rare and mainly diagnosed at autopsy. Acute Budd-Chiari syndrome is a recognized cause of acute liver failure and has been associated with several rare cardiac tumors: atrial myxoma, caval rhabdomyosarcoma, and primary cardiac adenocarcinoma. We present the first case of a fatal, highly differentiated cardiac synovial sarcoma that presented as acute liver failure from Budd-Chiari syndrome. PMID- 26157958 TI - Protein-Losing Gastroenteropathy Associated With Sjogren's Syndrome: First Known Case Reported Outside of Asia. AB - Protein-losing gastroenteropathy (PLGE) is a rare extraglandular manifestation of Sjogren's syndrome, reported in fewer than 10 cases. We report a 58-year-old white woman with Sjogren's syndrome, type 1 renal tubular acidosis, and PLGE, who presented with cachexia and 100-pound weight loss. The diagnosis was made based on hypoalbuminemia in the absence of significant proteinuria, low levels of fat soluble vitamins, low transferrin, and an elevated alpha-1 antitrypsin (A1AT) fecal clearance, supported by imaging and endoscopy, with biopsy showing lymphocytic infiltration. She was successfully treated with cyclophosphamide and prednisone. To our knowledge, this is the first such case outside of Asia. PMID- 26157959 TI - Lanthanum-Induced Gastrointestinal Histiocytosis. AB - A patient with end-stage renal disease (ESRD) on hemodialysis presented with fever, anorexia, and nausea shortly after starting oral lanthanum carbonate for phosphate control. Gastric and duodenal biopsies demonstrated diffuse histiocytosis with intracellular aggregates of basophilic foreign material. Transmission electron microscopy, an underutilized diagnostic test, revealed the nature of the aggregates as heavy metal particles, consistent with lanthanum. Symptoms and histiocytosis improved after discontinuation of lanthanum. Lanthanum may be an underdiagnosed cause of gastrointestinal histiocytosis. PMID- 26157960 TI - Primary Pancreatic Lymphoma Simulating Acute Cholestatic Hepatitis in a 7-Year Old Child. AB - Primary pancreatic lymphoma in children has been described infrequently in literature, and its acute presentation as cholestatic hepatitis is similarly rare. We report a case of a 7-year-old child with primary pancreatic lymphoma presenting as acute infective hepatitis, leading to delay in correct diagnosis and management. PMID- 26157961 TI - Welcome to Neurophotonics. PMID- 26157962 TI - The BRAIN Initiative. PMID- 26157963 TI - Programmable wireless light-emitting diode stimulator for chronic stimulation of optogenetic molecules in freely moving mice. AB - We produced a miniaturized, multicode, multiband, and programmable light-emitting diode (LED) stimulator for wireless control of optogenetic experiments. The LED stimulator is capable of driving three independent LEDs upon reception of an infrared (IR) signal generated by a custom-made IR transmitter. Individual LED photopulse patterns are assigned to different codes of the IR signals (up to 256 codes). The photopulse patterns can be programmed in the on-board microcontroller by specifying the parameters of duration ([Formula: see text]), frequency ([Formula: see text]), and pulse width ([Formula: see text]). The IR signals were modulated at multiple carrier frequencies to establish multiband IR transmission. Using these devices, we could remotely control the moving direction of a Thy1 ChR2-YFP transgenic mouse by transcranially illuminating the corresponding hemisphere of the primary motor cortex. IR transmitter and LED stimulator will be particularly useful in experiments where free movement or patterned concurrent stimulation is desired, such as testing social communication of rodents. PMID- 26157965 TI - Improving neurovascular outcomes with bilateral forepaw stimulation in a rat photothrombotic ischemic stroke model. AB - Restoring perfusion to the penumbra during the hyperacute phase of ischemic stroke is a key goal of neuroprotection. Thrombolysis is currently the only approved treatment for ischemic stroke. However, its use is limited by the narrow therapeutic window and side effect of bleeding. Therefore, other interventions are desired that could potentially increase the perfusion of the penumbra. Here, we hypothesized that bilateral peripheral electrical stimulation will improve cerebral perfusion and restore cortical neurovascular response. We assess the outcomes of bilateral forepaw electrical stimulation at intensities of 2 and 4 mA, administered either unilaterally or bilaterally. We developed a combined electrocorticogram (ECoG)-functional photoacoustic microscopy (fPAM) system to evaluate the relative changes in cerebral hemodynamic function and electrophysiologic response to acute, focal stroke. The fPAM system is used for cerebral blood volume (CBV) and hemoglobin oxygen saturation ([Formula: see text]) and the ECoG for neural activity, namely somatosensory-evoked potential (SSEP), interhemispheric coherence, and alpha-delta ratio (ADR) in response to forepaw stimulation. Our results confirmed the neuroprotective effect of bilateral forepaw stimulation at 2 mA as indicated by the 82% recovery of ADR and 95% improvement in perfusion into the region of penumbra. This experimental model can be used to study other potential interventions such as therapeutic hypertension and hypercarbia. PMID- 26157966 TI - Alternating current and infrared produce an onset-free reversible nerve block. AB - Nerve block can eliminate spasms and chronic pain. Kilohertz frequency alternating current (KHFAC) produces a safe and reversible nerve block. However, KHFAC-induced nerve block is associated with an undesirable onset response. Optical inhibition using infrared (IR) laser light can produce nerve block without an onset response, but heats nerves. Combining KHFAC with IR inhibition [alternating current and infrared (ACIR)] produces a rapidly reversible nerve block without an onset response. ACIR can be used to rapidly and reversibly provide onset-free nerve block in the unmyelinated nerves of the marine mollusk Aplysia californica and may have significant advantages over either modality alone. ACIR may be of great clinical utility in the future. PMID- 26157964 TI - Single-cell imaging tools for brain energy metabolism: a review. AB - Neurophotonics comes to light at a time in which advances in microscopy and improved calcium reporters are paving the way toward high-resolution functional mapping of the brain. This review relates to a parallel revolution in metabolism. We argue that metabolism needs to be approached both in vitro and in vivo, and that it does not just exist as a low-level platform but is also a relevant player in information processing. In recent years, genetically encoded fluorescent nanosensors have been introduced to measure glucose, glutamate, ATP, NADH, lactate, and pyruvate in mammalian cells. Reporting relative metabolite levels, absolute concentrations, and metabolic fluxes, these sensors are instrumental for the discovery of new molecular mechanisms. Sensors continue to be developed, which together with a continued improvement in protein expression strategies and new imaging technologies, herald an exciting era of high-resolution characterization of metabolism in the brain and other organs. PMID- 26157967 TI - Infrared neural stimulation: a new stimulation tool for central nervous system applications. AB - The traditional approach to modulating brain function (in both clinical and basic science applications) is to tap into the neural circuitry using electrical currents applied via implanted electrodes. However, it suffers from a number of problems, including the risk of tissue trauma, poor spatial specificity, and the inability to selectively stimulate neuronal subtypes. About a decade ago, optical alternatives to electrical stimulation started to emerge in order to address the shortcomings of electrical stimulation. We describe the use of one optical stimulation technique, infrared neural stimulation (INS), during which short (of the order of a millisecond) pulses of infrared light are delivered to the neural tissue. Very focal stimulation is achieved via a thermal mechanism and stimulation location can be quickly adjusted by redirecting the light. After describing some of the work done in the peripheral nervous system, we focus on the use of INS in the central nervous system to investigate functional connectivity in the visual and somatosensory areas, target specific functional domains, and influence behavior of an awake nonhuman primate. We conclude with a positive outlook for INS as a tool for safe and precise targeted brain stimulation. PMID- 26157968 TI - Multiscale vision model for event detection and reconstruction in two-photon imaging data. AB - Reliable detection of calcium waves in multiphoton imaging data is challenging because of the low signal-to-noise ratio and because of the unpredictability of the time and location of these spontaneous events. This paper describes our approach to calcium wave detection and reconstruction based on a modified multiscale vision model, an object detection framework based on the thresholding of wavelet coefficients and hierarchical trees of significant coefficients followed by nonlinear iterative partial object reconstruction, for the analysis of two-photon calcium imaging data. The framework is discussed in the context of detection and reconstruction of intercellular glial calcium waves. We extend the framework by a different decomposition algorithm and iterative reconstruction of the detected objects. Comparison with several popular state-of-the-art image denoising methods shows that performance of the multiscale vision model is similar in the denoising, but provides a better segmenation of the image into meaningful objects, whereas other methods need to be combined with dedicated thresholding and segmentation utilities. PMID- 26157969 TI - Combined two-photon imaging, electrophysiological, and anatomical investigation of the human neocortex in vitro. AB - Spontaneous synchronous population activity (SPA) can be detected by electrophysiological methods in cortical slices of epileptic patients, maintained in a physiological medium in vitro. In order to gain additional spatial information about the network mechanisms involved in the SPA generation, we combined electrophysiological studies with two-photon imaging. Neocortical slices prepared from postoperative tissue of epileptic and tumor patients were maintained in a dual perfusion chamber in a physiological incubation medium. SPA was recorded with a 24-channel extracellular linear microelectrode covering all neocortical layers. After identifying the electrophysiologically active regions of the slice, bolus loading of neuronal and glial markers was applied on the tissue. SPA-related [Formula: see text] transients were detected in a large population of neighboring neurons with two-photon microscopy, simultaneous with extracellular SPA and intracellular whole-cell patch-clamp recordings. The intracellularly recorded cells were filled for subsequent anatomy. The cells were reconstructed in three dimensions and examined with light- and transmission electron microscopy. Combining high spatial resolution two-photon [Formula: see text] imaging techniques and high temporal resolution extra- and intracellular electrophysiology with cellular anatomy may permit a deeper understanding of the structural and functional properties of the human neocortex. PMID- 26157970 TI - Characterization of the BAC Id3-enhanced green fluorescent protein transgenic mouse line for in vivo imaging of astrocytes. AB - Astrocytes are highly ramified glial cells with critical roles in brain physiology and pathology. Recently, breakthroughs in imaging technology have expanded our understanding of astrocyte function in vivo. The in vivo study of astrocytic dynamics, however, is limited by the tools available to label astrocytes and their processes. Here, we characterize the bacterial artificial chromosome transgenic Id3-EGFP knock-in mouse to establish its usefulness for in vivo imaging of astrocyte processes. Using fixed brain sections, we observed enhanced green fluorescent protein expression in astrocytes and blood vessel walls throughout the brain, although the extent and cell type specificity of expression depended on the brain area and developmental age. Using in vivo two photon imaging, we visualized astrocytes in cortical layers 1-3 in both thin skull and window preparations. In adult animals, astrocytic cell bodies and fine processes could be followed over many hours. Our results suggest that Id3 mice could be used for in vivo imaging of astrocytes and blood vessels in development and adulthood. PMID- 26157972 TI - Short-channel functional near-infrared spectroscopy regressions improve when source-detector separation is reduced. AB - In functional near-infrared spectroscopy (fNIRS) of human cerebral hemodynamics, dedicated surface-sensitive recording channels are useful for regressing out background hemodynamics and isolating activation-specific responses. A wide variety of source-detector separations have been utilized for this purpose. Here, we report a direct comparison of regression performance between two extremes of the reported range, 13 and 6 mm. Measurements of visual stimulation response (flickering radial checkerboard) were obtained from nine adults using a standard commercial source-detector grid with 13-mm diagonals, into which three extra detector fibers were placed to provide 6-mm channels at certain locations. When the NIRS recordings (17 total trials) were processed, the contrast-to-noise ratio was significantly higher with 6-mm regression channels than with 13 mm. The advantage could be due in part to the undesired sensing of brain activity by the 13-mm channels. We suggest that shorter distances be considered for optimal removal of superficial hemodynamics in NIRS signals from the adult brain. PMID- 26157971 TI - Neuropharmacological effect of methylphenidate on attention network in children with attention deficit hyperactivity disorder during oddball paradigms as assessed using functional near-infrared spectroscopy. AB - The current study aimed to explore the neural substrate for methylphenidate effects on attentional control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS), which can be applied to young children with ADHD more easily than conventional neuroimaging modalities. Using fNIRS, we monitored the oxy hemoglobin signal changes of 22 ADHD children (6 to 14 years old) performing an oddball task before and 1.5 h after methylphenidate or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Twenty-two age- and gender-matched normal controls without methylphenidate administration were also monitored. In the control subjects, the oddball task recruited the right prefrontal and inferior parietal cortices, and this activation was absent in premedicated ADHD children. The reduced right prefrontal activation was normalized after methylphenidate but not placebo administration in ADHD children. These results are consistent with the neuropharmacological effects of methylphenidate to upregulate the dopamine system in the prefrontal cortex innervating from the ventral tegmentum (mesocortical pathway), but not the noradrenergic system from the parietal cortex to the locus coeruleus. Thus, right prefrontal activation would serve as an objective neurofunctional biomarker to indicate the effectiveness of methylphenidate on ADHD children in attentional control. fNIRS monitoring enhances early clinical diagnosis and the treatment of ADHD children, especially those with an inattention phenotype. PMID- 26157973 TI - Optimizing the general linear model for functional near-infrared spectroscopy: an adaptive hemodynamic response function approach. AB - An increasing number of functional near-infrared spectroscopy (fNIRS) studies utilize a general linear model (GLM) approach, which serves as a standard statistical method for functional magnetic resonance imaging (fMRI) data analysis. While fMRI solely measures the blood oxygen level dependent (BOLD) signal, fNIRS measures the changes of oxy-hemoglobin (oxy-Hb) and deoxy hemoglobin (deoxy-Hb) signals at a temporal resolution severalfold higher. This suggests the necessity of adjusting the temporal parameters of a GLM for fNIRS signals. Thus, we devised a GLM-based method utilizing an adaptive hemodynamic response function (HRF). We sought the optimum temporal parameters to best explain the observed time series data during verbal fluency and naming tasks. The peak delay of the HRF was systematically changed to achieve the best-fit model for the observed oxy- and deoxy-Hb time series data. The optimized peak delay showed different values for each Hb signal and task. When the optimized peak delays were adopted, the deoxy-Hb data yielded comparable activations with similar statistical power and spatial patterns to oxy-Hb data. The adaptive HRF method could suitably explain the behaviors of both Hb parameters during tasks with the different cognitive loads during a time course, and thus would serve as an objective method to fully utilize the temporal structures of all fNIRS data. PMID- 26157974 TI - Intraoperative laser speckle contrast imaging with retrospective motion correction for quantitative assessment of cerebral blood flow. AB - Although multiple intraoperative cerebral blood flow (CBF) monitoring techniques are currently available, a quantitative method that allows for continuous monitoring and that can be easily integrated into the surgical workflow is still needed. Laser speckle contrast imaging (LSCI) is an optical imaging technique with a high spatiotemporal resolution that has been recently demonstrated as feasible and effective for intraoperative monitoring of CBF during neurosurgical procedures. This study demonstrates the impact of retrospective motion correction on the quantitative analysis of intraoperatively acquired LSCI images. LSCI images were acquired through a surgical microscope during brain tumor resection procedures from 10 patients under baseline conditions and after a cortical stimulation in three of those patients. The patient's electrocardiogram (ECG) was recorded during acquisition for postprocess correction of pulsatile artifacts. Automatic image registration was retrospectively performed to correct for tissue motion artifacts, and the performance of rigid and nonrigid transformations was compared. In baseline cases, the original images had [Formula: see text] noise across 16 regions of interest (ROIs). ECG filtering moderately reduced the noise to [Formula: see text], while image registration resulted in a further noise reduction of [Formula: see text]. Combined ECG filtering and image registration significantly reduced the noise to [Formula: see text] ([Formula: see text]). Using the combined motion correction, accuracy and sensitivity to small changes in CBF were improved in cortical stimulation cases. There was also excellent agreement between rigid and nonrigid registration methods (15/16 ROIs with [Formula: see text] difference). Results from this study demonstrate the importance of motion correction for improved visualization of CBF changes in clinical LSCI images. PMID- 26157975 TI - Neurophotonics Visibility, Indexing, and Impact. PMID- 26157977 TI - Greater contribution of cerebral than extracerebral hemodynamics to near-infrared spectroscopy signals for functional activation and resting-state connectivity in infants. AB - While near-infrared spectroscopy (NIRS) has been increasingly applied to neuroimaging and functional connectivity studies in infants, it has not been quantitatively examined as to what extent the deep tissue (such as cerebral tissue) as opposed to shallow tissue (such as scalp), contributes to NIRS signals measured in infants. A method for separating the effects of deep- and shallow tissue layers was applied to data of nine sleeping three-month-old infants who had been exposed to 3-s speech sounds or silence (i.e., resting state) and whose hemodynamic changes over their bilateral temporal cortices had been measured by using an NIRS system with multiple source-detector (S-D) distances. The deep layer contribution was found to be large during resting [67% at S-D 20 mm, 78% at S-D 30 mm for oxygenated hemoglobin (oxy-Hb)] as well as during the speech condition (72% at S-D 20 mm, 82% at S-D 30 mm for oxy-Hb). A left-right connectivity analysis showed that correlation coefficients between left and right channels did not differ between original- and deep-layer signals under no stimulus conditions and that of original- and deep-layer signals were larger than those of the shallow layer. These results suggest that NIRS signals obtained in infants with appropriate S-D distances largely reflected cerebral hemodynamic changes. PMID- 26157976 TI - Review of quantitative phase-digital holographic microscopy: promising novel imaging technique to resolve neuronal network activity and identify cellular biomarkers of psychiatric disorders. AB - Quantitative phase microscopy (QPM) has recently emerged as a new powerful quantitative imaging technique well suited to noninvasively explore a transparent specimen with a nanometric axial sensitivity. In this review, we expose the recent developments of quantitative phase-digital holographic microscopy (QP DHM). Quantitative phase-digital holographic microscopy (QP-DHM) represents an important and efficient quantitative phase method to explore cell structure and dynamics. In a second part, the most relevant QPM applications in the field of cell biology are summarized. A particular emphasis is placed on the original biological information, which can be derived from the quantitative phase signal. In a third part, recent applications obtained, with QP-DHM in the field of cellular neuroscience, namely the possibility to optically resolve neuronal network activity and spine dynamics, are presented. Furthermore, potential applications of QPM related to psychiatry through the identification of new and original cell biomarkers that, when combined with a range of other biomarkers, could significantly contribute to the determination of high risk developmental trajectories for psychiatric disorders, are discussed. PMID- 26157978 TI - Test-retest reliability of functional near infrared spectroscopy in infants. AB - There has been a rapid rise in the number of publications using functional near infrared spectroscopy (fNIRS) for human developmental research over the past decade. However test-retest reliability of this measure of brain activation in infants remains unknown. To assess this, we utilized data from a longitudinal cohort who participated in an fNIRS study on social perception at two age points. Thirteen infants had valid data from two sessions held 8.5 months apart (4 to 8 months and 12 to 16 months). Inter- and intrasession fNIRS test-retest reliability was assessed at the individual and group levels using the oxyhemoglobin ([Formula: see text]) signal. Infant compliance with the study was similar in both sessions (assessed by the proportion of time infants looked to the stimuli), and there was minimal discrepancy in sensor placement over the targeted area between sessions. At the group level, good spatial overlap of significant responses and signal reliability was seen (spatial overlap was 0.941 and average signal change within an region of interest was [Formula: see text]). At participant level, spatial overlap was acceptable ([Formula: see text] on average across infants) although signal reliability varied between participants. This first study of test-retest reliability of fNIRS in infants shows encouraging results, particularly for group-based analysis. PMID- 26157979 TI - Neuropharmacological effect of atomoxetine on attention network in children with attention deficit hyperactivity disorder during oddball paradigms as assessed using functional near-infrared spectroscopy. AB - The current study aimed to explore the neural substrate for atomoxetine effects on attentional control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS), which can be applied to young children with ADHD more easily than conventional neuroimaging modalities. Using fNIRS, we monitored the oxy hemoglobin signal changes of 15 ADHD children (6 to 14 years old) performing an oddball task before and 1.5 h after atomoxetine or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Fifteen age-, gender-, and intelligence quotient-matched normal controls without atomoxetine administration were also monitored. In the control subjects, the oddball task recruited the right prefrontal and inferior parietal cortices. The right prefrontal and parietal activation was normalized after atomoxetine administration in ADHD children. This was in contrast to our previous study using a similar protocol showing methylphenidate-induced normalization of only the right prefrontal function. fNIRS allows the detection of differential neuropharmacological profiles of both substances in the attentional network: the neuropharmacological effects of atomoxetine to upregulate the noradrenergic system reflected in the right prefrontal and inferior parietal activations and those of methylphenidate to upregulate the dopamine system reflected in the prefrontal cortex activation. PMID- 26157980 TI - Motion tracking and electromyography-assisted identification of mirror hand contributions to functional near-infrared spectroscopy images acquired during a finger-tapping task performed by children with cerebral palsy. AB - Recent studies have demonstrated functional near-infrared spectroscopy (fNIRS) to be a viable and sensitive method for imaging sensorimotor cortex activity in children with cerebral palsy (CP). However, during unilateral finger tapping, children with CP often exhibit unintended motions in the nontapping hand, known as mirror motions, which confuse the interpretation of resulting fNIRS images. This work presents a method for separating some of the mirror motion contributions to fNIRS images and demonstrates its application to fNIRS data from four children with CP performing a finger-tapping task with mirror motions. Finger motion and arm muscle activity were measured simultaneously with fNIRS signals using motion tracking and electromyography (EMG), respectively. Subsequently, subject-specific regressors were created from the motion capture or EMG data and independent component analysis was combined with a general linear model to create an fNIRS image representing activation due to the tapping hand and one image representing activation due to the mirror hand. The proposed method can provide information on how mirror motions contribute to fNIRS images, and in some cases, it helps remove mirror motion contamination from the tapping hand activation images. PMID- 26157981 TI - Differential effects of early postinjury treatment with neuroprotective drugs in a mouse model using diffuse reflectance spectroscopy. AB - The time required for the arrival of an ambulance crew and administration of first aid is critical to clinical outcome, particularly in the case of head injury victims requiring neuroprotective drugs following a car accident, falls, and assaults. Short response times of the medical team, together with proper treatment, can limit injury severity and even save a life before transportation to the nearest medical center. We present a comparative evaluation of five different neuroprotective drugs frequently used in intensive care and operating units in the early phase following traumatic brain injury (TBI): hypertonic saline (HTS), mannitol, morphine, melatonin, and minocycline. The effectiveness of these drugs in terms of changes in brain tissue morphology (cell organelle size, density, distribution, etc.) and biochemical tissue properties (chromophores' content) was experimentally evaluated through analysis of the spectral reduced scattering and optical absorption coefficient parameters in the near-infrared (NIR) optical range (650 to 1000 nm). Experiments were conducted on anesthetized male mice subjected to a noninvasive closed head weight-drop model of focal TBI ([Formula: see text] and [Formula: see text] control) and monitored using an NIR diffuse reflectance spectroscopy system utilizing independent source detector separation and location. After 10 min of baseline measurement, focal TBI was induced and measurements were conducted for 20 min. Subsequently, a neuroprotective drug was administrated and measurements were recorded for another 30 min. This work's major findings are threefold: first, minocycline was found to improve hemodynamic outcome at the earliest time postinjury. Second, HTS decreased brain water content and inhibited the increase in intracranial pressure. Third, the efficacy of neuroprotective drugs can be monitored noninvasively with diffuse reflectance spectroscopy. The demonstrated ability to noninvasively detect cerebral physiological properties following early administration of neuroprotective drugs underlines the need for more extensive investigation of the combined use of clinical drugs in larger-scale preclinical experiments to find the most beneficial drug treatment for brain injury patients. PMID- 26157982 TI - Exploring effective multiplicity in multichannel functional near-infrared spectroscopy using eigenvalues of correlation matrices. AB - Recent advances in multichannel functional near-infrared spectroscopy (fNIRS) allow wide coverage of cortical areas while entailing the necessity to control family-wise errors (FWEs) due to increased multiplicity. Conventionally, the Bonferroni method has been used to control FWE. While Type I errors (false positives) can be strictly controlled, the application of a large number of channel settings may inflate the chance of Type II errors (false negatives). The Bonferroni-based methods are especially stringent in controlling Type I errors of the most activated channel with the smallest [Formula: see text] value. To maintain a balance between Types I and II errors, effective multiplicity ([Formula: see text]) derived from the eigenvalues of correlation matrices is a method that has been introduced in genetic studies. Thus, we explored its feasibility in multichannel fNIRS studies. Applying the [Formula: see text] method to three kinds of experimental data with different activation profiles, we performed resampling simulations and found that [Formula: see text] was controlled at 10 to 15 in a 44-channel setting. Consequently, the number of significantly activated channels remained almost constant regardless of the number of measured channels. We demonstrated that the [Formula: see text] approach can be an effective alternative to Bonferroni-based methods for multichannel fNIRS studies. PMID- 26157983 TI - Concurrent fNIRS-fMRI measurement to validate a method for separating deep and shallow fNIRS signals by using multidistance optodes. AB - It has been reported that a functional near-infrared spectroscopy (fNIRS) signal can be contaminated by extracerebral contributions. Many algorithms using multidistance separations to address this issue have been proposed, but their spatial separation performance has rarely been validated with simultaneous measurements of fNIRS and functional magnetic resonance imaging (fMRI). We previously proposed a method for discriminating between deep and shallow contributions in fNIRS signals, referred to as the multidistance independent component analysis (MD-ICA) method. In this study, to validate the MD-ICA method from the spatial aspect, multidistance fNIRS, fMRI, and laser-Doppler-flowmetry signals were simultaneously obtained for 12 healthy adult males during three tasks. The fNIRS signal was separated into deep and shallow signals by using the MD-ICA method, and the correlation between the waveforms of the separated fNIRS signals and the gray matter blood oxygenation level-dependent signals was analyzed. A three-way analysis of variance ([Formula: see text]) indicated that the main effect of fNIRS signal depth on the correlation is significant [[Formula: see text], [Formula: see text]]. This result indicates that the MD-ICA method successfully separates fNIRS signals into spatially deep and shallow signals, and the accuracy and reliability of the fNIRS signal will be improved with the method. PMID- 26157984 TI - High-throughput spatial light modulation two-photon microscopy for fast functional imaging. AB - The optical monitoring of multiple single neuron activities requires high throughput parallel acquisition of signals at millisecond temporal resolution. To this aim, holographic two-photon microscopy (2PM) based on spatial light modulators (SLMs) has been developed in combination with standard laser scanning microscopes. This requires complex coordinate transformations for the generation of holographic patterns illuminating the points of interest. We present a simpler and fully digital setup (SLM-2PM) which collects three-dimensional two-photon images by only exploiting the SLM. This configuration leads to an accurate placement of laser beamlets over small focal volumes, eliminating mechanically moving parts and making the system stable over long acquisition times. Fluorescence signals are diffraction limited and are acquired through a pixelated detector, setting the actual limit to the acquisition rate. High-resolution structural images were acquired by raster-scanning the sample with a regular grid of excitation focal volumes. These images allowed the selection of the structures to be further investigated through an interactive operator-guided selection process. Functional signals were collected by illuminating all the preselected points with a single hologram. This process is exemplified for high-speed (up to 1 kHz) two-photon calcium imaging on acute cerebellar slices. PMID- 26157985 TI - Rat embryonic hippocampus and induced pluripotent stem cell derived cultured neurons recover from laser-induced subaxotomy. AB - Axonal injury and stress have long been thought to play a pathogenic role in a variety of neurodegenerative diseases. However, a model for studying single-cell axonal injury in mammalian cells and the processes of repair has not been established. The purpose of this study was to examine the response of neuronal growth cones to laser-induced axonal damage in cultures of embryonic rat hippocampal neurons and induced pluripotent stem cell (iPSC) derived human neurons. A 532-nm pulsed [Formula: see text] picosecond laser was focused to a diffraction limited spot at a precise location on an axon using a laser energy/power that did not rupture the cell membrane (subaxotomy). Subsequent time series images were taken to follow axonal recovery and growth cone dynamics. After laser subaxotomy, axons thinned at the damage site and initiated a dynamic cytoskeletal remodeling process to restore axonal thickness. The growth cone was observed to play a role in the repair process in both hippocampal and iPSC derived neurons. Immunofluorescence staining confirmed structural tubulin damage and revealed initial phases of actin-based cytoskeletal remodeling at the damage site. The results of this study indicate that there is a repeatable and cross species repair response of axons and growth cones after laser-induced damage. PMID- 26157988 TI - Neurophotonics Pioneers and News. PMID- 26157986 TI - Infrared neural stimulation of human spinal nerve roots in vivo. AB - Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans. PMID- 26157987 TI - Multimodal reconstruction of microvascular-flow distributions using combined two photon microscopy and Doppler optical coherence tomography. AB - Computing microvascular cerebral blood flow ([Formula: see text]) in real cortical angiograms is challenging. Here, we investigated whether the use of Doppler optical coherence tomography (DOCT) flow measurements in individual vessel segments can help in reconstructing [Formula: see text] across the entire vasculature of a truncated cortical angiogram. A [Formula: see text] computational framework integrating DOCT measurements is presented. Simulations performed on a synthetic angiogram showed that the addition of DOCT measurements, especially close to large inflowing or outflowing vessels, reduces the impact of pressure boundary conditions and estimated vessel resistances resulting in a more accurate reconstruction of [Formula: see text]. Our technique was then applied to reconstruct microvascular flow distributions in the mouse cortex down to [Formula: see text] by combining two-photon laser scanning microscopy angiography with DOCT. PMID- 26157990 TI - Montreal SfNIRS conference shines light on the brain. PMID- 26157992 TI - Pioneers in Neurophotonics: Special Section Honoring Professor Lawrence B. Cohen. PMID- 26157991 TI - Anatomical guidance for functional near-infrared spectroscopy: AtlasViewer tutorial. AB - Functional near-infrared spectroscopy (fNIRS) is an optical imaging method that is used to noninvasively measure cerebral hemoglobin concentration changes induced by brain activation. Using structural guidance in fNIRS research enhances interpretation of results and facilitates making comparisons between studies. AtlasViewer is an open-source software package we have developed that incorporates multiple spatial registration tools to enable structural guidance in the interpretation of fNIRS studies. We introduce the reader to the layout of the AtlasViewer graphical user interface, the folder structure, and user files required in the creation of fNIRS probes containing sources and detectors registered to desired locations on the head, evaluating probe fabrication error and intersubject probe placement variability, and different procedures for estimating measurement sensitivity to different brain regions as well as image reconstruction performance. Further, we detail how AtlasViewer provides a generic head atlas for guiding interpretation of fNIRS results, but also permits users to provide subject-specific head anatomies to interpret their results. We anticipate that AtlasViewer will be a valuable tool in improving the anatomical interpretation of fNIRS studies. PMID- 26157993 TI - Personal recollections: regarding the pioneer days of optical recording of membrane potential using voltage-sensitive dyes. PMID- 26157994 TI - Larry Cohen, indomitable pioneer. PMID- 26157995 TI - Larry Cohen-50 ways to DYE your science. PMID- 26157996 TI - Imaging with organic indicators and high-speed charge-coupled device cameras in neurons: some applications where these classic techniques have advantages. AB - Dynamic calcium and voltage imaging is a major tool in modern cellular neuroscience. Since the beginning of their use over 40 years ago, there have been major improvements in indicators, microscopes, imaging systems, and computers. While cutting edge research has trended toward the use of genetically encoded calcium or voltage indicators, two-photon microscopes, and in vivo preparations, it is worth noting that some questions still may be best approached using more classical methodologies and preparations. In this review, we highlight a few examples in neurons where the combination of charge-coupled device (CCD) imaging and classical organic indicators has revealed information that has so far been more informative than results using the more modern systems. These experiments take advantage of the high frame rates, sensitivity, and spatial integration of the best CCD cameras. These cameras can respond to the faster kinetics of organic voltage and calcium indicators, which closely reflect the fast dynamics of the underlying cellular events. PMID- 26157997 TI - Branch specific and spike-order specific action potential invasion in basal, oblique, and apical dendrites of cortical pyramidal neurons. AB - In neocortical pyramidal neurons, action potentials (APs) propagate from the axon into the dendritic tree to influence distal synapses. Traditionally, AP backpropagation was studied in the thick apical trunk. Here, we used the principles of optical imaging developed by Cohen to investigate AP invasion into thin dendritic branches (basal, oblique, and tuft) of prefrontal cortical L5 pyramidal neurons. Multisite optical recordings from neighboring dendrites revealed a clear dichotomy between two seemingly equal dendritic branches belonging to the same cell ("sister branches"). We documented the variable efficacy of AP invasion in basal and oblique branches by revealing their AP voltage waveforms. Using fast multisite calcium imaging, we found that trains of APs are filtered differently between two apical tuft branches. Although one dendritic branch passes all spikes in an AP train, another branch belonging to the same neuron, same cortical layer, and same path distance from the cell body, experiences only one spike. Our data indicate that the vast differences in dendritic voltage and calcium transients, detected in dendrites of pyramidal neurons, arise from a nonuniform distribution of A-type [Formula: see text] conductance, an aggregate number of branch points in the path of the AP propagation and minute differences in dendritic diameter. PMID- 26157998 TI - Computer-generated holography enhances voltage dye fluorescence discrimination in adjacent neuronal structures. AB - Voltage-sensitive fluorescence indicators enable tracking neuronal electrical signals simultaneously in multiple neurons or neuronal subcompartments difficult to access with patch electrodes. However, efficient widefield epifluorescence detection of rapid voltage fluorescence transients necessitates that imaged cells and structures lie sufficiently far from other labeled structures to avoid contamination from out of focal plane and scattered light. We overcame this limitation by exciting dye fluorescence with one-photon computer-generated holography shapes contoured to axons or dendrites of interest, enabling widefield detection of voltage fluorescence with high spatial specificity. By shaping light onto neighboring axons and dendrites, we observed that dendritic back-propagating action potentials were broader and slowly rising compared with axonal action potentials, differences not measured in the same structures illuminated with a large "pseudowidefield" (pWF) spot of the same excitation density. Shaped illumination trials showed reduced baseline fluorescence, higher baseline noise, and fractional fluorescence transient amplitudes two times greater than trials acquired with pWF illumination of the same regions. PMID- 26157999 TI - Voltage-sensitive dye imaging during functional development of the embryonic nervous system: a brief review with special thanks to Professor Larry Cohen. AB - Investigating the developmental organization of the embryonic nervous system is one of the major challenges in the field of neuroscience. Despite their significance, functional studies on the vertebrate embryonic central nervous system (CNS) have been hampered by the technical limitations associated with conventional electrophysiological methods. The advent of optical techniques using voltage-sensitive dyes, which were developed by Dr. Cohen and his colleagues, has enabled electrical activity in living cells to be monitored noninvasively and also facilitated the simultaneous recording of neural responses from multiple regions. Using optical recording techniques, it is now possible to follow the functional organization of the embryonic CNS and image the spatiotemporal dynamics involved in the formation of this neural network. We herein briefly reviewed optical studies on the embryonic CNS with a special emphasis on methodological considerations and the study of neuronal circuit formation, which demonstrates the utility of fast voltage-sensitive dye imaging as a powerful tool for elucidating the functional organization of the embryonic CNS. PMID- 26158000 TI - Using simultaneous voltage and calcium imaging to study fast Ca(2+) channels. AB - The combination of fluorescence measurements of membrane potential and intracellular [Formula: see text] concentration allows correlating the electrical and calcium activity of a cell with spatial precision. The technical advances allowing this type of measurement were achieved only recently and represent an important step in the progress of the voltage imaging approach pioneered over 40 years ago by Lawrence B. Cohen. Here, we show how this approach can be used to investigate the function of [Formula: see text] channels using the foreseen possibility to extract [Formula: see text] currents from imaging experiments. The kinetics of the [Formula: see text] current, mediated by voltage-gated [Formula: see text] channels, can be accurately derived from the [Formula: see text] fluorescence measurement using [Formula: see text] indicators with [Formula: see text] that equilibrate in [Formula: see text]. In this respect, the imaging apparatus dedicated to this application is described in detail. Next, we illustrate the mathematical procedure to extract the current from the [Formula: see text] fluorescence change, including a method to calibrate the signal to charge flux density. Finally, we show an example of simultaneous membrane potential and [Formula: see text] optical measurement associated with an action potential at a CA1 hippocampal pyramidal neuron from a mouse brain slice. The advantages and limitations of this approach are discussed. PMID- 26158001 TI - Optical recording of calcium currents during impulse conduction in cardiac tissue. AB - We explore the feasibility of obtaining a spatially resolved picture of [Formula: see text] inward currents ([Formula: see text]) in multicellular cardiac tissue by differentiating optically recorded [Formula: see text] transients that accompany propagating action potentials. Patterned growth strands of neonatal rat ventricular cardiomyocytes were stained with the [Formula: see text] indicators Fluo-4 or Fluo-4FF. Preparations were stimulated at 1 Hz, and [Formula: see text] transients were recorded with high spatiotemporal resolution ([Formula: see text], 2 kHz analog bandwidth) with a photodiode array. Signals were differentiated after appropriate digital filtering. Differentiation of [Formula: see text] transients resulted in optically recorded calcium currents (ORCCs) that carried the temporal and pharmacological signatures of L-type [Formula: see text] inward currents: the time to peak amounted to [Formula: see text] (Fluo-4FF) and [Formula: see text] (Fluo-4), full-width at half-maximum was [Formula: see text], and ORCCs were completely suppressed by [Formula: see text][Formula: see text]. Also, and as reported before from patch-clamp studies, caffeine reversibly depressed the amplitude of ORCCs. The results demonstrate that the differentiation of [Formula: see text] transients can be used to obtain a spatially resolved picture of the initial phase of [Formula: see text] in cardiac tissue and to assess relative changes of activation/fast inactivation of [Formula: see text] following pharmacological interventions. PMID- 26158002 TI - Linker length and fusion site composition improve the optical signal of genetically encoded fluorescent voltage sensors. AB - Several genetically encoded fluorescent sensors of voltage were created by systematically truncating the length of the linker sequence between the voltage sensing domain and the position of the fluorescent protein, Super Ecliptic A227D. In addition to varying the length, the amino acid composition at the fusion site for the fluorescent protein was modified. Both linker length and amino acid composition affected the size and voltage sensitivity of the optical signal. The truncation mutants revealed a potential structural periodicity with a maximum signal three amino acids from the voltage-sensing domain and another maximum 11 amino acids from the voltage-sensing domain. These results confirm that the linker length and composition can fine tune the size and voltage range of the sensor. The potential periodicity suggests that the orientation of the fluorescent protein could be important for improving the signal size implicating dimerization of the fluorescent protein. PMID- 26158003 TI - All-optical mapping of barrel cortex circuits based on simultaneous voltage sensitive dye imaging and channelrhodopsin-mediated photostimulation. AB - We describe an experimental approach that uses light to both control and detect neuronal activity in mouse barrel cortex slices: blue light patterned by a digital micromirror array system allowed us to photostimulate specific layers and columns, while a red-shifted voltage-sensitive dye was used to map out large scale circuit activity. We demonstrate that such all-optical mapping can interrogate various circuits in somatosensory cortex by sequentially activating different layers and columns. Further, mapping in slices from whisker-deprived mice demonstrated that chronic sensory deprivation did not significantly alter feedforward inhibition driven by layer 5 pyramidal neurons. Further development of voltage-sensitive optical probes should allow this all-optical mapping approach to become an important and high-throughput tool for mapping circuit interactions in the brain. PMID- 26158004 TI - Comparison of genetically encoded calcium indicators for monitoring action potentials in mammalian brain by two-photon excitation fluorescence microscopy. AB - Imaging calcium transients associated with neuronal activity has yielded important insights into neural physiology. Genetically encoded calcium indicators (GECIs) offer conspicuous potential advantages for this purpose, including exquisite targeting. While the catalogue of available GECIs is steadily growing, many newly developed sensors that appear promising in vitro or in model cells appear to be less useful when expressed in mammalian neurons. We have, therefore, evaluated the performance of GECIs from two of the most promising families of sensors, G-CaMPs [Nat. Biotechnol.2(2), 137-141 (2001)] and GECOs [Science2(2), 1888-1891 (2011)], for monitoring action potentials in rat brain. Specifically, we used two-photon excitation fluorescence microscopy to compare calcium transients detected by G-CaMP3; GCaMP6f; G-CaMP7; Green-GECO1.0, 1.1 and 1.2; Blue-GECO; Red-GECO; Rex-GECO0.9; Rex-GECO1; Carmine-GECO; Orange-GECO; and Yellow-GECO1s. After optimizing excitation wavelengths, we monitored fluorescence signals associated with increasing numbers of action potentials evoked by current injection in CA1 pyramidal neurons in rat organotypic hippocampal slices. Some GECIs, particularly Green-GECO1.2, GCaMP6f, and G-CaMP7, were able to detect single action potentials with high reliability. By virtue of greatest sensitivity and fast kinetics, G-CaMP7 may be the best currently available GECI for monitoring calcium transients in mammalian neurons. PMID- 26158005 TI - Usability and performance-informed selection of personalized mental tasks for an online near-infrared spectroscopy brain-computer interface. AB - Brain-computer interfaces (BCIs) allow individuals to use only cognitive activities to interact with their environment. The widespread use of BCIs is limited, due in part to their lack of user-friendliness. The main goal of this work was to develop a more user-centered BCI and determine if: (1) individuals can acquire control of an online near-infrared spectroscopy BCI via usability and performance-informed selection of mental tasks without compromising classification accuracy and (2) the combination of usability and performance informed selection of mental tasks yields subjective ease-of-use ratings that exceed those attainable with prescribed mental tasks. Twenty able-bodied participants were recruited. Half of the participants served as a control group, using the state-of-the-art prescribed mental strategies. The other half of the participants comprised the study group, choosing their own personalized mental strategies out of eleven possible tasks. It was concluded that users were, in fact, able to acquire control of the more user-centered BCI without a significant change in accuracy compared to the prescribed task BCI. Furthermore, the personalized BCI yielded higher subjective ease-of-use ratings than the prescribed BCI. Average online accuracies of [Formula: see text] and [Formula: see text] were achieved by the personalized and prescribed mental task groups, respectively. PMID- 26158006 TI - Target structures for cochlear infrared neural stimulation. AB - Infrared neural stimulation (INS) is a method to depolarize neurons with infrared light. While consensus exists that heating of the target structure is essential, subsequent steps that result in the generation of an action potential are controversially discussed in the literature. The question of whether cochlear INS is an acoustic event has not been clarified. Results have been published that could be explained solely by an acoustic event. However, data exist that do not support an acoustical stimulus as the dominant factor in cochlear INS. We review the different findings that have been suggested for the mechanism of INS. Furthermore, we present the data that clarify the role of an acoustical event in cochlear INS. Masking experiments have been performed in hearing, hearing impaired, and severely hearing impaired animals. In normal hearing animals, the laser response could be masked by the acoustic stimulus. Once thresholds to acoustic stimuli were elevated, the ability to acoustically mask the INS response gradually disappeared. Thresholds for acoustic stimuli were significantly elevated in animals with compromised cochlear function, while the thresholds for optical stimulation remained largely unchanged. The results suggest that the direct interaction between the radiation and the target structure dominates cochlear INS. PMID- 26158007 TI - Determination of epileptic focus side in mesial temporal lobe epilepsy using long term noninvasive fNIRS/EEG monitoring for presurgical evaluation. AB - Noninvasive localization of an epileptogenic zone is a fundamental step for presurgical evaluation of epileptic patients. Here, we applied long-term simultaneous functional near-infrared spectroscopy (fNIRS)/electroencephalogram (EEG) monitoring for focus diagnosis in patients with mesial temporal lobe epilepsy (MTLE). Six MTLE patients underwent long-term (8-16 h per day for 4 days) fNIRS/EEG monitoring for the occurrence of spontaneous seizures. Four spontaneous seizures were successfully recorded out of the six patients. To determine oxy-Hb amplitude, the period-average values of oxy-Hb across 20 s from the EEG- or clinically defined epileptic onset were calculated for both hemispheres from the simultaneously recorded fNIRS data. The average oxy-Hb values for the temporal lobe at the earlier EEG- or clinically defined epileptic onsets were greater for the epileptic side than for the contralateral side after EEG activity suppression, spike train, and clinical seizure in all four cases. The true laterality was determined based on the relief of seizures by selective amygdalo-hippocampectomy. Thus, oxy-Hb amplitude could be a reliable measure for determining the epileptic focus side. Long-term simultaneous fNIRS/EEG measurement serves as an effective tool for recording spontaneous seizures. Cerebral hemodynamic measurement by fNIRS would serve as a valuable supplementary noninvasive measurement method for presurgical evaluation of MTLE. PMID- 26158008 TI - Artifact reduction in long-term monitoring of cerebral hemodynamics using near infrared spectroscopy. AB - Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging technique used to assess cerebral hemodynamics. Its portability, ease of use, and relatively low operational cost lend itself well to the long-term monitoring of hemodynamic changes, such as those in epilepsy, where events are unpredictable. Long-term monitoring is associated with challenges including alterations in behaviors and motion that can result in artifacts. Five patients with epilepsy were assessed for interictal hemodynamic changes and alterations in behavior or motion. Based on this work, visual inspection was used to identify NIRS artifacts during a period of interest, specifically prior to seizures, in four patients. A motion artifact reduction algorithm (MARA, also known as the spline interpolation method) was tested on these data. Alterations in the NIRS measurements often occurred simultaneously with changes in motion and behavior. Occasionally, sharp shift artifacts were observed in the data. When artifacts appeared as sustained baseline shifts in the data, MARA reduced the standard deviation of the data and the appearance improved. We discussed motion and artifacts as challenges associated with long-term monitoring of cerebral hemodynamics in patients with epilepsy and our group's approach to circumvent these challenges and improve the quality of the data collected. PMID- 26158009 TI - How short is short? Optimum source-detector distance for short-separation channels in functional near-infrared spectroscopy. AB - In recent years, it has been demonstrated that using functional near-infrared spectroscopy (fNIRS) channels with short separations to explicitly sample extra cerebral tissues can provide a significant improvement in the accuracy and reliability of fNIRS measurements. The aim of these short-separation channels is to measure the same superficial hemodynamics observed by standard fNIRS channels while also being insensitive to the brain. We use Monte Carlo simulations of photon transport in anatomically informed multilayer models to determine the optimum source-detector distance for short-separation channels in adult and newborn populations. We present a look-up plot that provides (for an acceptable value of short-separation channel brain sensitivity relative to standard channel brain sensitivity) the optimum short-separation distance. Though values vary across the scalp, when the acceptable ratio of the short-separation channel brain sensitivity to standard channel brain sensitivity is set at 5%, the optimum short separation distance is 8.4 mm in the typical adult and 2.15 mm in the term-age infant. PMID- 26158010 TI - Vasodynamics of pial and penetrating arterioles in relation to arteriolo arteriolar anastomosis after focal stroke. AB - Changes in blood perfusion in highly interconnected pial arterioles provide important insights about the vascular response to ischemia within brain. The functional role of arteriolo-arteriolar anastomosis (AAA) in regulating blood perfusion through penetrating arterioles is yet to be discovered. We apply a label-free optical microangiography (OMAG) technique to evaluate the changes in vessel lumen diameter and red blood cell velocity among a large number of pial and penetrating arterioles within AAA abundant region overlaying the penumbra in the parietal cortex after a middle cerebral artery occlusion (MCAO). In comparison with two-photon microscopy, the OMAG technique makes it possible to image a large number of vessels in a short period of time without administering exogenous contrast agents during a time-constrained MCAO experiment. We compare vasodynamics in penetrating arterioles at various locations. The results show that the MCA connected penetrating arterioles close to a strong AAA dilate, while those belonging to a region away from AAAs constrict in various degrees. These results suggest AAAs play a major role in supporting the active dilation of the penetrating arterioles, thus compensating a significant amount of blood to the ischemic region, whereas the poor blood perfusion occurs at the regions away from AAA connections, leading to ischemia. PMID- 26158011 TI - Modified toolbox for optogenetics in the nonhuman primate. AB - Attracted by the appealing advantages of optogenetics, many nonhuman primate labs are attempting to incorporate this technique in their experiments. Despite some reported successes by a few groups, many still find it difficult to develop a reliable way to transduce cells in the monkey brain and subsequently monitor light-induced neuronal activity. Here, we describe a methodology that we have developed and successfully deployed on a regular basis with multiple monkeys. All devices and accessories are easy to obtain and results using these have been proven to be highly replicable. We developed the "in-chair" viral injection system and used tapered and thinner fibers for optical stimulation, which significantly improved the efficacy and reduced tissue damage. With these methods, we have successfully transduced cells in multiple monkeys in both deep and shallow cortical areas. We could reliably obtain neural modulation for months after injection, and no light-induced artifacts were observed during recordings. Further experiments using these methods have shown that optogenetic stimulation can be used to bias spatial attention in a visual choice discrimination task in a way comparable to electrical microstimulation, which demonstrates the potential use of our methods in both fundamental research and clinical applications. PMID- 26158013 TI - Optogenetics for suppression of cardiac electrical activity in human and rat cardiomyocyte cultures. AB - Optogenetics has revolutionized neuroscience by enabling precise control of neural excitation. The development of similar optogenetics strategies in the heart is just emerging and mainly focused on pacing with light activation of channelrhodopsin-2. Here, we aimed to develop an optogenetic approach to suppress local cardiac electrical activity by using engineered cell-grafts (HEK293-cells) transfected to express the light-sensitive hyperpolarizing proton-pump archaerhodopsin-3 (Arch3). To evaluate the ability of the engineered cells to couple and modulate the electrical activity of cardiomyocytes, we co-cultured the Arch3-HEK293 cells with neonatal rat cardiomyocytes (NRCMs) or human embryonic stem cells derived cardiomyocytes (hESC-CMs). The co-cultures' conduction and chronotropic properties were evaluated prior, during, and following application of focused monochromatic light (590 nm) using a multielectrode array mapping system. Application of focused illumination completely silenced electrical activity at the illuminated area in all NRCM co-cultures, leading to development of localized functional conduction blocks. Similarly, illumination significantly slowed spontaneous beating-rate in the hESCs-CMs co-cultures (from [Formula: see text] to [Formula: see text], [Formula: see text]). Interestingly, a transient acceleration in beating-rate was noted immediately postillumination. In conclusion, a combined gene and cell therapy approach, using light-sensitive hyperpolarizing proteins, could be used to modulate conduction and automaticity in cardiomyocyte cultures, opening the way for future optogenetic treatments for cardiac tachyarrhythmias. PMID- 26158012 TI - Red fluorescent proteins (RFPs) and RFP-based biosensors for neuronal imaging applications. AB - The inherent advantages of red-shifted fluorescent proteins and fluorescent protein-based biosensors for the study of signaling processes in neurons and other tissues have motivated the development of a plethora of new tools. Relative to green fluorescent proteins (GFPs) and other blue-shifted alternatives, red fluorescent proteins (RFPs) provide the inherent advantages of lower phototoxicity, lower autofluorescence, and deeper tissue penetration associated with longer wavelength excitation light. All other factors being the same, the multiple benefits of using RFPs make these tools seemingly ideal candidates for use in neurons and, ultimately, the brain. However, for many applications, the practical utility of RFPs still falls short of the preferred GFPs. We present an overview of RFPs and RFP-based biosensors, with an emphasis on their reported applications in neuroscience. PMID- 26158014 TI - Optrodes for combined optogenetics and electrophysiology in live animals. AB - Optical tissue properties limit visible light depth penetration in tissue. Because of this, the recent development of optogenetic tools was quickly followed by the development of light delivery devices for in vivo optogenetics applications. We summarize the efforts made in the last decade to design neural probes that combine conventional electrophysiological recordings and optical channel(s) for optogenetic activation, often referred to as optodes or optrodes. Several aspects including challenges for light delivery in living brain tissue, the combination of light delivery with electrophysiological recordings, probe designs, multimodality, wireless implantable system, and practical considerations guiding the choice of configuration depending on the questions one seeks to address are presented. PMID- 26158015 TI - Evolution of optogenetic microdevices. AB - Implementation of optogenetic techniques is a recent addition to the neuroscientists' preclinical research arsenal, helping to expose the intricate connectivity of the brain and allowing for on-demand direct modulation of specific neural pathways. Developing an optogenetic system requires thorough investigation of the optogenetic technique and of previously fabricated devices, which this review accommodates. Many experiments utilize bench-top systems that are bulky, expensive, and necessitate tethering to the animal. However, these bench-top systems can make use of power-demanding technologies, such as concurrent electrical recording. Newer portable microdevices and implantable systems carried by freely moving animals are being fabricated that take advantage of wireless energy harvesting to power a system and allow for natural movements that are vital for behavioral testing and analysis. An investigation of the evolution of tethered, portable, and implantable optogenetic microdevices is presented, and an analysis of benefits and detriments of each system, including optical power output, device dimensions, electrode width, and weight is given. Opsins, light sources, and optical fiber coupling are also discussed to optimize device parameters and maximize efficiency from the light source to the fiber, respectively. These attributes are important considerations when designing and developing improved optogenetic microdevices. PMID- 26158016 TI - Pericyte structure and distribution in the cerebral cortex revealed by high resolution imaging of transgenic mice. AB - Pericytes are essential for normal brain function, but many aspects of their physiology remain enigmatic due to a lack of tools to genetically target this cell population. Here, we characterize brain pericytes using two existing Cre recombinase driver mouse lines that can serve distinct purposes in cerebrovascular research. One line expresses an inducible version of Cre under the NG2 proteoglycan promoter, which provides the sparse labeling necessary to define the morphology of single cells. These mice reveal structural differences between pericytes adjacent to arterioles versus those broadly distributed in the capillary bed that may underlie differential roles in control of vessel caliber. A second line expresses Cre constitutively under the platelet-derived growth factor receptor beta promoter and provides continuous, highly specific and near complete labeling of pericytes and myocytes along the entire cerebrovasculature. This line provides a three-dimensional view of pericyte distribution along the cortical angioarchitecture following optical clearing of brain tissue. In combination with recent reporter lines for expression of optogenetic actuators and activity-sensitive probes, these mice may be key tools for studying pericyte biology in the intact brain. PMID- 26158017 TI - Photonics meets connectomics: case of diffuse, long-range horizontal projections in rat cortex. AB - Recent years have seen progress in characterizing connections between different regions of the rodent brain to establish a "connectome." This effort involves systematically collected new data together with tools to characterize network relationships in new and preexisting data. The choices made during data collection, analysis, and display in order to generate these connectomes have emphasized dense, specific connections between cortical regions defined using a priori parcellation schemes that may obscure certain spatial relationships in the data. One example of a pattern of connectivity not clearly evident in these connectomes is a diffusely radiating, apparently nonspecific, border-crossing, long-range horizontal axonal projection that is related to horizontal spreads of evoked activity in the rat cortex. Here, we describe the horizontal projection system and explore evidence for this projection within the connectome data. We consider how the differences in optical and histological methodologies and analyses used for the connectome studies and our own studies lead to different emphases concerning this important horizontal projection pattern. PMID- 26158018 TI - Comprehensive optical and data management infrastructure for high-throughput light-sheet microscopy of whole mouse brains. AB - Comprehensive mapping and quantification of neuronal projections in the central nervous system requires high-throughput imaging of large volumes with microscopic resolution. To this end, we have developed a confocal light-sheet microscope that has been optimized for three-dimensional (3-D) imaging of structurally intact clarified whole-mount mouse brains. We describe the optical and electromechanical arrangement of the microscope and give details on the organization of the microscope management software. The software orchestrates all components of the microscope, coordinates critical timing and synchronization, and has been written in a versatile and modular structure using the LabVIEW language. It can easily be adapted and integrated to other microscope systems and has been made freely available to the light-sheet community. The tremendous amount of data routinely generated by light-sheet microscopy further requires novel strategies for data handling and storage. To complete the full imaging pipeline of our high throughput microscope, we further elaborate on big data management from streaming of raw images up to stitching of 3-D datasets. The mesoscale neuroanatomy imaged at micron-scale resolution in those datasets allows characterization and quantification of neuronal projections in unsectioned mouse brains. PMID- 26158020 TI - Welcome to the Journal of Medical Imaging. PMID- 26158019 TI - Network analysis of mesoscale optical recordings to assess regional, functional connectivity. AB - With modern optical imaging methods, it is possible to map structural and functional connectivity. Optical imaging studies that aim to describe large-scale neural connectivity often need to handle large and complex datasets. In order to interpret these datasets, new methods for analyzing structural and functional connectivity are being developed. Recently, network analysis, based on graph theory, has been used to describe and quantify brain connectivity in both experimental and clinical studies. We outline how to apply regional, functional network analysis to mesoscale optical imaging using voltage-sensitive-dye imaging and channelrhodopsin-2 stimulation in a mouse model. We include links to sample datasets and an analysis script. The analyses we employ can be applied to other types of fluorescence wide-field imaging, including genetically encoded calcium indicators, to assess network properties. We discuss the benefits and limitations of using network analysis for interpreting optical imaging data and define network properties that may be used to compare across preparations or other manipulations such as animal models of disease. PMID- 26158021 TI - Quality evaluation of digital fundus images through combined measures. AB - The evaluation of image quality is an important step before an automatic analysis of retinal images. Several conditions can impair the acquisition of a good image, and minimum image quality requirements should be present to ensure that an automatic or semiautomatic system provides an accurate diagnosis. A method to classify fundus images as low or good quality is presented. The method starts with the detection of regions of uneven illumination and evaluates if the segmented noise masks affect a clinically relevant area (around the macula). Afterwards, focus is evaluated through a fuzzy classifier. An input vector is created extracting three focus features. The system was validated in a large dataset (1454 fundus images), obtained from an online database and an eye clinic and compared with the ratings of three observers. The system performance was close to optimal with an area under the receiver operating characteristic curve of 0.9943. PMID- 26158022 TI - Generalized method for partial volume estimation and tissue segmentation in cerebral magnetic resonance images. AB - An artifact found in magnetic resonance images (MRI) called partial volume averaging (PVA) has received much attention since accurate segmentation of cerebral anatomy and pathology is impeded by this artifact. Traditional neurological segmentation techniques rely on Gaussian mixture models to handle noise and PVA, or high-dimensional feature sets that exploit redundancy in multispectral datasets. Unfortunately, model-based techniques may not be optimal for images with non-Gaussian noise distributions and/or pathology, and multispectral techniques model probabilities instead of the partial volume (PV) fraction. For robust segmentation, a PV fraction estimation approach is developed for cerebral MRI that does not depend on predetermined intensity distribution models or multispectral scans. Instead, the PV fraction is estimated directly from each image using an adaptively defined global edge map constructed by exploiting a relationship between edge content and PVA. The final PVA map is used to segment anatomy and pathology with subvoxel accuracy. Validation on simulated and real, pathology-free T1 MRI (Gaussian noise), as well as pathological fluid attenuation inversion recovery MRI (non-Gaussian noise), demonstrate that the PV fraction is accurately estimated and the resultant segmentation is robust. Comparison to model-based methods further highlight the benefits of the current approach. PMID- 26158023 TI - Multiframe registration of real-time three-dimensional echocardiography time series. AB - Mosaicing of real-time three-dimensional echocardiography (RT3-DE) images aims at extending the field-of-view of overlapping images. Currently available methods discard most of the temporal information available in the time series. We investigate the added value of simultaneous registration of multiple temporal frames using common similarity metrics. We combine RT3-DE images of the left and right ventricles by registration and fusion. The standard approach of registering single frames, either end-diastolic (ED) or end-systolic (ES), is compared with simultaneous registration of multiple time frames, to evaluate the effect of using the information from all images in the metric. A transformation estimating the protocol-specific misalignment is used to initialize the registration. It is shown that multiframe registration can be as accurate as alignment of the images based on manual annotations. Multiframe registration using normalized cross correlation outperforms any of the single-frame methods. As opposed to expectations, extending the multiframe registration beyond simultaneous use of ED and ES frames does not further improve registration results. PMID- 26158024 TI - Automatic nuclear cataract grading using image gradients. AB - This paper deals with automatic grading of nuclear cataract (NC) from slit-lamp images in order to reduce the efforts in traditional manual grading. Existing works on this topic have mostly used brightness and color of the eye lens for the task but not the visibility of lens parts. The main contribution of this paper is in utilizing the visibility cue by proposing gray level image gradient-based features for automatic grading of NC. Gradients are important for the task because in a healthy eye, clear visibility of lens parts leads to distinct edges in the lens region, but these edges fade as severity of cataract increases. Experiments performed on a large dataset of over 5000 slit-lamp images reveal that the proposed features perform better than the state-of-the-art features in terms of both speed and accuracy. Moreover, fusion of the proposed features with the prior ones gives results better than any of the two used alone. PMID- 26158025 TI - Forecasting new development of tumor areas using spatial and temporal distribution profiles of hemoglobin saturation in a mouse model. AB - Features of the tumor microenvironment (TME), such as hemoglobin saturation (HbSat), can provide valuable information on early development and progression of tumors. HbSat correlates with high metabolism and precedes the formation of angiogenic tumors; therefore, changes in HbSat profile can be used as a biomarker for early cancer detection. In this project, we develop a methodology to evaluate HbSat for forecasting early tumor development in a mouse model. We built a delta ([Formula: see text]) cumulative feature that includes spatial and temporal distribution of HbSat for classifying tumor/normal areas. Using a two-class (normal and tumor) logistic regression, the [Formula: see text] feature successfully forecasts tumor areas in two window chamber mice ([Formula: see text] and 0.85). To assess the performance of the logistic regression-based classifier utilizing the [Formula: see text] feature of each region, we conduct a 10-fold cross-validation analysis (AUC of the [Formula: see text]). These results show that the TME features based on HbSat can be used to evaluate tumor progression and forecast new occurrences of tumor areas. PMID- 26158026 TI - Improved depth perception with three-dimensional auxiliary display and computer generated three-dimensional panoramic overviews in robot-assisted laparoscopy. AB - In comparison to open surgery, endoscopic surgery offers impaired depth perception and narrower field-of-view. To improve depth perception, the Da Vinci robot offers three-dimensional (3-D) video on the console for the surgeon but not for assistants, although both must collaborate. We improved the shared perception of the whole surgical team by connecting live 3-D monitors to all three available Da Vinci generations, probed user experience after two years by questionnaire, and compared time measurements of a predefined complex interaction task performed with a 3-D monitor versus two-dimensional. Additionally, we investigated whether the complex mental task of reconstructing a 3-D overview from an endoscopic video can be performed by a computer and shared among users. During the study, 925 robot-assisted laparoscopic procedures were performed in three hospitals, including prostatectomies, cystectomies, and nephrectomies. Thirty-one users participated in our questionnaire. Eighty-four percent preferred 3-D monitors and 100% reported spatial-perception improvement. All participating urologists indicated quicker performance of tasks requiring delicate collaboration (e.g., clip placement) when assistants used 3-D monitors. Eighteen users participated in a timing experiment during a delicate cooperation task in vitro. Teamwork was significantly (40%) faster with the 3-D monitor. Computer-generated 3-D reconstructions from recordings offered very wide interactive panoramas with educational value, although the present embodiment is vulnerable to movement artifacts. PMID- 26158027 TI - Automatic planning of atrial fibrillation ablation lines using landmark constrained nonrigid registration. AB - Catheter ablation is a common treatment option for drug-refractory atrial fibrillation. In many cases, pulmonary vein isolation is the treatment of choice. With current fluoro overlay methods or electroanatomic mapping systems, it is possible to visualize three-dimensional (3-D) anatomy as well as target ablation lines to provide additional context information. Today, however, these lines need to be set manually before the procedure by the physician, which may interrupt the clinical workflow. As a solution, we present an automatic approach for the planning of ablation target lines. Our method works on surface models extracted from 3-D images. To propose suitable ablation lines, a reference model annotated with reference ablation lines is nonrigidly registered to the model segmented from a new patient's 3-D data. After registration, the reference plan is transferred from the reference anatomy to the individual patient anatomy. Due to the high anatomical variations observed in clinical practice, additional landmark constraints are employed in the registration process to increase the robustness of our approach. We evaluated our method on 43 clinical datasets by benchmarking it against professionally planned ablation lines and achieved an average error over all datasets of [Formula: see text]. A qualitative evaluation of the ablation planning lines matched clinical expectations. PMID- 26158028 TI - Influence of study design in receiver operating characteristics studies: sequential versus independent reading. AB - Observer studies to assess new image processing devices or computer-aided diagnosis techniques are often performed, but little is known about the effect of the study design on observer performance results. We investigated the effect of the sequential and independent reading design on observer study results with respect to reader performance and their statistical power. For this we performed an observer study for the detection of lung nodules with bone-suppressed images (BSIs) compared with original chest radiographs. In a fully crossed observer study, eight observers assessed a series of 300 radiographs four times, including one assessment of the original radiograph with sequential BSI and two independent reading sessions with BSI. Observer performance was compared using multireader multicase receiver operating characteristics. No significant difference between the effect of BSI in the sequential and the independent reading sessions could be found ([Formula: see text]; [Formula: see text]). Compared with the original radiographs, increased performance with BSI was significant in the sequential and one of the independent reading sessions ([Formula: see text]; [Formula: see text]), and nonsignificant in the other independent reading session ([Formula: see text]). A strong increase of uncorrelated variance components was found in the independent reading sessions, masking the ability to demonstrate differences in observer performance across modalities. Therefore, the sequential reading design is the preferred design because it is less burdensome and has more statistical power. PMID- 26158029 TI - Detection of the spatial accuracy of a magnetic resonance and surgical computed tomography scanner in the region of surgical interest. AB - In image-guided surgeries (IGSs) and radiology, images are the main source of information. As image data provide the differentiation between normal and abnormal tissues in the human, the images need to be reliable and they need to provide accurate spatial representation of the patient. This research concentrates on the accuracy assessment of IGS devices in general and then specifically on the spatial accuracy of a common magnetic resonance (MR) imager and a mobile three-dimensional surgical computed tomography (CT) scanner. The accuracy assessment tool had been designed to be universal and to enable its use in the hospital setting. In this study, it was used in detecting the spatial accuracy of a commercial surgical CT scanner, the O-arm, and a 1.5-T MR imager. The results show the tendency of magnetic resonance imaging to produce slight decreases in spatial accuracy toward the fringes of the images from the isocenter. Furthermore, the results indicate that the accuracy of both scanners was within pixel size and thus highly accurate in the region of surgical interest of this study. PMID- 26158030 TI - Number of mammography cases read per year is a strong predictor of sensitivity. AB - Early detection of breast cancers affects the 5-year recurrence rates and treatment options for diagnosed patients, and consequently, many countries have instituted nationwide screening programs. This study compared the performance of expert radiologists from Australia and the United States in detection of breast cancer. Forty-one radiologists, 21 from Australia and 20 from the United States, reviewed 30 mammographic cases containing two-view mammograms. Twenty cases had abnormal findings and 10 cases had normal findings. Radiologists were asked to locate malignancies and assign a level of confidence. A jackknife free-response receiver operating characteristic, figure of merit (JAFROC, FOM), inferred receiver operating characteristic, area under curve (ROC, AUC), specificity, sensitivity, and location sensitivity were calculated using Ziltron software and JAFROC v4.1. A Mann-Whitney U test was used to compare the performance of Australian and U.S. radiologists. The results showed that when experience and the number of mammograms read per year were taken into account, the Australian radiologists sampled showed significantly higher sensitivity and location sensitivity ([Formula: see text]). JAFROC (FOM) and inferred ROC (AUC) analysis showed no difference between the overall performance of the two countries. ROC (AUC) and location sensitivity were higher for the Australian radiologists who read the most cases per year. PMID- 26158031 TI - Clinical cross-polarization optical coherence tomography assessment of subsurface enamel below dental resin composite restorations. AB - A newly designed intraoral swept source cross-polarization optical coherence tomography (CP-OCT) imaging system was used to examine the integrity of the subsurface enamel below resin composite restorations placed in primary teeth. CP OCT analysis was performed using images obtained from resin composite restoration in 62 ([Formula: see text]) pediatric subjects. Clinical examination was performed by a single examiner prior to CP-OCT imaging and analysis. CP-OCT images are presented using a unique combined intensity image, where a false color scale is overlaid on the grayscale intensity image. There was a clear difference in the distribution of the mean-backscattered intensity (mR) between restorations recently placed and those possessing frank cavitation (Student's t-test, [Formula: see text]). For mR above 15.49 dB, the sensitivity was 80% and specificity 86%. The Youden index J was 0.8 above 12.3 dB where sensitivity was 100% and specificity was 80%. CP-OCT imaging may be used to confirm the subsurface marginal integrity below resin composite restorations but with careful consideration of limitations of the imaging modality. CP-OCT imaging may be a useful adjunct to clinical visual investigation to confirm that a composite margin has a sound and well-adapted interface. PMID- 26158032 TI - Three-dimensional DNA image cytometry by optical projection tomographic microscopy for early cancer diagnosis. AB - Aneuploidy is typically assessed by flow cytometry (FCM) and image cytometry (ICM). We used optical projection tomographic microscopy (OPTM) for assessing cellular DNA content using absorption and fluorescence stains. OPTM combines some of the attributes of both FCM and ICM and generates isometric high-resolution three-dimensional (3-D) images of single cells. Although the depth of field of the microscope objective was in the submicron range, it was extended by scanning the objective's focal plane. The extended depth of field image is similar to a projection in a conventional x-ray computed tomography. These projections were later reconstructed using computed tomography methods to form a 3-D image. We also present an automated method for 3-D nuclear segmentation. Nuclei of chicken, trout, and triploid trout erythrocyte were used to calibrate OPTM. Ratios of integrated optical densities extracted from 50 images of each standard were compared to ratios of DNA indices from FCM. A comparison of mean square errors with thionin, hematoxylin, Feulgen, and SYTOX green was done. Feulgen technique was preferred as it showed highest stoichiometry, least variance, and preserved nuclear morphology in 3-D. The addition of this quantitative biomarker could further strengthen existing classifiers and improve early diagnosis of cancer using 3-D microscopy. PMID- 26158033 TI - Exciting Progress in the Growth of JMI. PMID- 26158034 TI - Accurate and reliable segmentation of the optic disc in digital fundus images. AB - We describe a complete pipeline for the detection and accurate automatic segmentation of the optic disc in digital fundus images. This procedure provides separation of vascular information and accurate inpainting of vessel-removed images, symmetry-based optic disc localization, and fitting of incrementally complex contour models at increasing resolutions using information related to inpainted images and vessel masks. Validation experiments, performed on a large dataset of images of healthy and pathological eyes, annotated by experts and partially graded with a quality label, demonstrate the good performances of the proposed approach. The method is able to detect the optic disc and trace its contours better than the other systems presented in the literature and tested on the same data. The average error in the obtained contour masks is reasonably close to the interoperator errors and suitable for practical applications. The optic disc segmentation pipeline is currently integrated in a complete software suite for the semiautomatic quantification of retinal vessel properties from fundus camera images (VAMPIRE). PMID- 26158035 TI - Global image registration using a symmetric block-matching approach. AB - Most medical image registration algorithms suffer from a directionality bias that has been shown to largely impact subsequent analyses. Several approaches have been proposed in the literature to address this bias in the context of nonlinear registration, but little work has been done for global registration. We propose a symmetric approach based on a block-matching technique and least-trimmed square regression. The proposed method is suitable for multimodal registration and is robust to outliers in the input images. The symmetric framework is compared with the original asymmetric block-matching technique and is shown to outperform it in terms of accuracy and robustness. The methodology presented in this article has been made available to the community as part of the NiftyReg open-source package. PMID- 26158036 TI - Incorporating texture features in a computer-aided breast lesion diagnosis system for automated three-dimensional breast ultrasound. AB - We investigated the benefits of incorporating texture features into an existing computer-aided diagnosis (CAD) system for classifying benign and malignant lesions in automated three-dimensional breast ultrasound images. The existing system takes into account 11 different features, describing different lesion properties; however, it does not include texture features. In this work, we expand the system by including texture features based on local binary patterns, gray level co-occurrence matrices, and Gabor filters computed from each lesion to be diagnosed. To deal with the resulting large number of features, we proposed a combination of feature-oriented classifiers combining each group of texture features into a single likelihood, resulting in three additional features used for the final classification. The classification was performed using support vector machine classifiers, and the evaluation was done with 10-fold cross validation on a dataset containing 424 lesions (239 benign and 185 malignant lesions). We compared the classification performance of the CAD system with and without texture features. The area under the receiver operating characteristic curve increased from 0.90 to 0.91 after adding texture features ([Formula: see text]). PMID- 26158037 TI - Change detection of medical images using dictionary learning techniques and principal component analysis. AB - Automatic change detection methods for identifying the changes of serial MR images taken at different times are of great interest to radiologists. The majority of existing change detection methods in medical imaging, and those of brain images in particular, include many preprocessing steps and rely mostly on statistical analysis of magnetic resonance imaging (MRI) scans. Although most methods utilize registration software, tissue classification remains a difficult and overwhelming task. Recently, dictionary learning techniques are being used in many areas of image processing, such as image surveillance, face recognition, remote sensing, and medical imaging. We present an improved version of the EigenBlockCD algorithm, named the EigenBlockCD-2. The EigenBlockCD-2 algorithm performs an initial global registration and identifies the changes between serial MR images of the brain. Blocks of pixels from a baseline scan are used to train local dictionaries to detect changes in the follow-up scan. We use PCA to reduce the dimensionality of the local dictionaries and the redundancy of data. Choosing the appropriate distance measure significantly affects the performance of our algorithm. We examine the differences between [Formula: see text] and [Formula: see text] norms as two possible similarity measures in the improved EigenBlockCD 2 algorithm. We show the advantages of the [Formula: see text] norm over the [Formula: see text] norm both theoretically and numerically. We also demonstrate the performance of the new EigenBlockCD-2 algorithm for detecting changes of MR images and compare our results with those provided in the recent literature. Experimental results with both simulated and real MRI scans show that our improved EigenBlockCD-2 algorithm outperforms the previous methods. It detects clinical changes while ignoring the changes due to the patient's position and other acquisition artifacts. PMID- 26158038 TI - In vivo reproducibility of robotic probe placement for a novel ultrasound-guided radiation therapy system. AB - Ultrasound can provide real-time image guidance of radiation therapy, but the probe-induced tissue deformations cause local deviations from the treatment plan. If placed during treatment planning, the probe causes streak artifacts in required computed tomography (CT) images. To overcome these challenges, we propose robot-assisted placement of an ultrasound probe, followed by replacement with a geometrically identical, CT-compatible model probe. In vivo reproducibility was investigated by implanting a canine prostate, liver, and pancreas with three 2.38-mm spherical markers in each organ. The real probe was placed to visualize the markers and subsequently replaced with the model probe. Each probe was automatically removed and returned to the same position or force. Under position control, the median three-dimensional reproducibility of marker positions was 0.6 to 0.7 mm, 0.3 to 0.6 mm, and 1.1 to 1.6 mm in the prostate, liver, and pancreas, respectively. Reproducibility was worse under force control. Probe substitution errors were smallest for the prostate (0.2 to 0.6 mm) and larger for the liver and pancreas (4.1 to 6.3 mm), where force control generally produced larger errors than position control. Results indicate that position control is better than force control for this application, and the robotic approach has potential, particularly for relatively constrained organs and reproducibility errors that are smaller than established treatment margins. PMID- 26158039 TI - Assessment of patient selection criteria for quantitative imaging with respiratory-gated positron emission tomography. AB - The objective of this investigation was to propose techniques for determining which patients are likely to benefit from quantitative respiratory-gated imaging by correlating respiratory patterns to changes in positron emission tomography (PET) metrics. Twenty-six lung and liver cancer patients underwent PET/computed tomography exams with recorded chest/abdominal displacements. Static and adaptive amplitude-gated [[Formula: see text]]fluoro-D-glucose (FDG) PET images were generated from list-mode acquisitions. Patients were grouped by respiratory pattern, lesion location, or degree of lesion attachment to anatomical structures. Respiratory pattern metrics were calculated during time intervals corresponding to PET field of views over lesions of interest. FDG PET images were quantified by lesion maximum standardized uptake value ([Formula: see text]). Relative changes in [Formula: see text] between static and gated PET images were tested for association to respiratory pattern metrics. Lower lung lesions and liver lesions had significantly higher changes in [Formula: see text] than upper lung lesions (14 versus 3%, [Formula: see text]). Correlation was highest ([Formula: see text], [Formula: see text], [Formula: see text]) between changes in [Formula: see text] and nonstandard respiratory pattern metrics. Lesion location had a significant impact on changes in PET quantification due to respiratory gating. Respiratory pattern metrics were correlated to changes in [Formula: see text], though sample size limited statistical power. Validation in larger cohorts may enable selection of patients prior to acquisition who would benefit from respiratory-gated PET imaging. PMID- 26158040 TI - Quantitative sparse array vascular elastography: the impact of tissue attenuation and modulus contrast on performance. AB - Quantitative sparse array vascular elastography visualizes the shear modulus distribution within vascular tissues, information that clinicans could use to reduce the number of strokes each year. However, the low transmit power sparse array (SA) imaging could hamper the clinical usefulness of the resulting elastograms. In this study, we evaluated the performance of modulus elastograms recovered from simulated and physical vessel phantoms with varying attenuation coefficients (0.6, 1.5, and [Formula: see text]) and modulus contrasts ([Formula: see text], [Formula: see text], and [Formula: see text]) using SA imaging relative to those obtained with conventional linear array (CLA) and plane-wave (PW) imaging techniques. Plaques were visible in all modulus elastograms, but those produced using SA and PW contained less artifacts. The modulus contrast-to noise ratio decreased rapidly with increasing modulus contrast and attenuation coefficient, but more quickly when SA imaging was performed than for CLA or PW. The errors incurred varied from 10.9% to 24% (CLA), 1.8% to 12% (SA), and [Formula: see text] (PW). Modulus elastograms produced with SA and PW imagings were not significantly different ([Formula: see text]). Despite the low transmit power, SA imaging can produce useful modulus elastograms in superficial organs, such as the carotid artery. PMID- 26158042 TI - Pioneers in Medical Imaging Series. PMID- 26158041 TI - Color accuracy and reproducibility in whole slide imaging scanners. AB - We propose a workflow for color reproduction in whole slide imaging (WSI) scanners, such that the colors in the scanned images match to the actual slide color and the inter-scanner variation is minimum. We describe a new method of preparation and verification of the color phantom slide, consisting of a standard IT8-target transmissive film, which is used in color calibrating and profiling the WSI scanner. We explore several International Color Consortium (ICC) compliant techniques in color calibration/profiling and rendering intents for translating the scanner specific colors to the standard display (sRGB) color space. Based on the quality of the color reproduction in histopathology slides, we propose the matrix-based calibration/profiling and absolute colorimetric rendering approach. The main advantage of the proposed workflow is that it is compliant to the ICC standard, applicable to color management systems in different platforms, and involves no external color measurement devices. We quantify color difference using the CIE-DeltaE2000 metric, where DeltaE values below 1 are considered imperceptible. Our evaluation on 14 phantom slides, manufactured according to the proposed method, shows an average inter-slide color difference below 1 DeltaE. The proposed workflow is implemented and evaluated in 35 WSI scanners developed at Philips, called the Ultra Fast Scanners (UFS). The color accuracy, measured as DeltaE between the scanner reproduced colors and the reference colorimetric values of the phantom patches, is improved on average to 3.5 DeltaE in calibrated scanners from 10 DeltaE in uncalibrated scanners. The average inter-scanner color difference is found to be 1.2 DeltaE. The improvement in color performance upon using the proposed method is apparent with the visual color quality of the tissue scans. PMID- 26158043 TI - Pioneers in Medical Imaging: Honoring the Memory of Robert F. Wagner. PMID- 26158044 TI - Nonparametric estimation receiver operating characteristic analysis for performance evaluation on combined detection and estimation tasks. AB - In an effort to generalize task-based assessment beyond traditional signal detection, there is a growing interest in performance evaluation for combined detection and estimation tasks, in which signal parameters, such as size, orientation, and contrast are unknown and must be estimated. One motivation for studying such tasks is their rich complexity, which offers potential advantages for imaging system optimization. To evaluate observer performance on combined detection and estimation tasks, Clarkson introduced the estimation receiver operating characteristic (EROC) curve and the area under the EROC curve as a summary figure of merit. This work provides practical tools for EROC analysis of experimental data. In particular, we propose nonparametric estimators for the EROC curve, the area under the EROC curve, and for the variance/covariance matrix of a vector of correlated EROC area estimates. In addition, we show that reliable confidence intervals can be obtained for EROC area, and we validate these intervals with Monte Carlo simulation. Application of our methodology is illustrated with an example comparing magnetic resonance imaging [Formula: see text]-space sampling trajectories. MATLAB(r) software implementing the EROC analysis estimators described in this work is publicly available at http://code.google.com/p/iqmodelo/. PMID- 26158045 TI - Energy weighting improves dose efficiency in clinical practice: implementation on a spectral photon-counting mammography system. AB - In x-ray imaging, contrast information content varies with photon energy. It is, therefore, possible to improve image quality by weighting photons according to energy. We have implemented and evaluated so-called energy weighting on a commercially available spectral photon-counting mammography system. The technique was evaluated using computer simulations, phantom experiments, and analysis of screening mammograms. The CNR benefit of energy weighting for a number of relevant target-background combinations measured by the three methods fell in the range of 2.2 to 5.2% when using optimal weight factors. This translates to a potential dose reduction at constant CNR in the range of 4.5 to 11%. We expect the choice of weight factor in practical implementations to be straightforward because (1) the CNR improvement was not very sensitive to weight, (2) the optimal weight was similar for all investigated target-background combinations, (3) aluminum/PMMA phantoms were found to represent clinically relevant tasks well, and (4) the optimal weight could be calculated directly from pixel values in phantom images. Reasonable agreement was found between the simulations and phantom measurements. Manual measurements on microcalcifications and automatic image analysis confirmed that the CNR improvement was detectable in energy weighted screening mammograms. PMID- 26158046 TI - Comparison of semiparametric receiver operating characteristic models on observer data. AB - The evaluation of medical imaging devices often involves studies that measure the ability of observers to perform a signal detection task on images obtained from those devices. Data from such studies are frequently regressed ordinally using two-sample receiver operating characteristic (ROC) models. We applied some of these models to a number of randomly chosen data sets from medical imaging and evaluated how well they fit using the Akaike and Bayesian information criteria and cross-validation. We find that for many observer data sets, a single parameter model is sufficient and that only some studies exhibit evidence for the use of models with more than a single parameter. In particular, the single parameter power-law model frequently well describes observer data. The power-law model has an asymmetric ROC curve and a constant mean-to-sigma ratio seen in studies analyzed with the bi-normal model. It is identical or very similar to special cases of other two-parameter models. PMID- 26158047 TI - Magnetization-prepared rapid acquisition with gradient echo magnetic resonance imaging signal and texture features for the prediction of mild cognitive impairment to Alzheimer's disease progression. AB - Early diagnoses of Alzheimer's disease (AD) would confer many benefits. Several biomarkers have been proposed to achieve such a task, where features extracted from magnetic resonance imaging (MRI) have played an important role. However, studies have focused exclusively on morphological characteristics. This study aims to determine whether features relating to the signal and texture of the image could predict mild cognitive impairment (MCI) to AD progression. Clinical, biological, and positron emission tomography information and MRI images of 62 subjects from the AD neuroimaging initiative were used in this study, extracting 4150 features from each MRI. Within this multimodal database, a feature selection algorithm was used to obtain an accurate and small logistic regression model, generated by a methodology that yielded a mean blind test accuracy of 0.79. This model included six features, five of them obtained from the MRI images, and one obtained from genotyping. A risk analysis divided the subjects into low-risk and high-risk groups according to a prognostic index. The groups were statistically different ([Formula: see text]). These results demonstrated that MRI features related to both signal and texture add MCI to AD predictive power, and supported the ongoing notion that multimodal biomarkers outperform single-modality ones. PMID- 26158048 TI - Generalized Roe and Metz receiver operating characteristic model: analytic link between simulated decision scores and empirical AUC variances and covariances. AB - Modeling and simulation are often used to understand and investigate random quantities and estimators. In 1997, Roe and Metz introduced a simulation model to validate analysis methods for the popular endpoint in reader studies to evaluate medical imaging devices, the reader-averaged area under the receiver operating characteristic (ROC) curve. Here, we generalize the notation of the model to allow more flexibility in recognition that variances of ROC ratings depend on modality and truth state. We also derive and validate equations for computing population variances and covariances for reader-averaged empirical AUC estimates under the generalized model. The equations are one-dimensional integrals that can be calculated using standard numerical integration techniques. This work provides the theoretical foundation and validation for a Java application called iRoeMetz that can simulate multireader multicase ROC studies and numerically calculate the corresponding variances and covariances of the empirical AUC. The iRoeMetz application and source code can be found at the "iMRMC" project on the google code project hosting site. These results and the application can be used by investigators to investigate ROC endpoints, validate analysis methods, and plan future studies. PMID- 26158049 TI - Cancer cell classification with coherent diffraction imaging using an extreme ultraviolet radiation source. AB - In cancer treatment, it is highly desirable to classify single cancer cells in real time. The standard method is polymerase chain reaction requiring a substantial amount of resources and time. Here, we present an innovative approach for rapidly classifying different cell types: we measure the diffraction pattern of a single cell illuminated with coherent extreme ultraviolet (XUV) laser generated radiation. These patterns allow distinguishing different breast cancer cell types in a subsequent step. Moreover, the morphology of the object can be retrieved from the diffraction pattern with submicron resolution. In a proof-of principle experiment, we prepared single MCF7 and SKBR3 breast cancer cells on gold-coated silica slides. The output of a laser-driven XUV light source is focused onto a single unstained and unlabeled cancer cell. With the resulting diffraction pattern, we could clearly identify the different cell types. With an improved setup, it will not only be feasible to classify circulating tumor cells with a high throughput, but also to identify smaller objects such as bacteria or even viruses. PMID- 26158050 TI - Comparative analysis of image-based phenotypes of mammographic density and parenchymal patterns in distinguishing between BRCA1/2 cases, unilateral cancer cases, and controls. AB - We statistically compare the contributions of parenchymal phenotypes to mammographic density in distinguishing between high-risk cases and low-risk controls. The age-matched evaluation included computerized mammographic assessment of breast percent density (PD) and parenchymal patterns (phenotypes of coarseness and contrast) from radiographic texture analysis (RTA) of the full field digital mammograms from 456 cases: 53 women with BRCA1/2 gene mutations, 75 with unilateral cancer, and 328 at low risk of developing breast cancer. Image based phenotypes of parenchymal pattern coarseness and contrast were each found to significantly discriminate between the groups; however, PD did not. From ROC analysis, PD alone yielded area under the fitted ROC curve (AUC) values of 0.53 ([Formula: see text]) and 0.57 ([Formula: see text]) in the classification task between BRCA1/2 gene-mutation carriers and low-risk women, and between unilateral cancer and low-risk women, respectively. In a round-robin evaluation with Bayesian artificial neural network (BANN) analysis, RTA yielded AUC values of 0.81 (95% confidence interval [0.71, 0.89]) and 0.70 (95% confidence interval [0.63, 0.77]) between the BRCA1/2 gene-mutation carriers and low-risk women, and between unilateral cancer and low-risk women, respectively. These results show that high-risk and low-risk women have different mammographic parenchymal patterns with significantly higher discrimination resulting from characteristics of the parenchymal patterns than just the breast PD. PMID- 26158051 TI - Multireader multicase reader studies with binary agreement data: simulation, analysis, validation, and sizing. AB - We treat multireader multicase (MRMC) reader studies for which a reader's diagnostic assessment is converted to binary agreement (1: agree with the truth state, 0: disagree with the truth state). We present a mathematical model for simulating binary MRMC data with a desired correlation structure across readers, cases, and two modalities, assuming the expected probability of agreement is equal for the two modalities ([Formula: see text]). This model can be used to validate the coverage probabilities of 95% confidence intervals (of [Formula: see text], [Formula: see text], or [Formula: see text] when [Formula: see text]), validate the type I error of a superiority hypothesis test, and size a noninferiority hypothesis test (which assumes [Formula: see text]). To illustrate the utility of our simulation model, we adapt the Obuchowski-Rockette-Hillis (ORH) method for the analysis of MRMC binary agreement data. Moreover, we use our simulation model to validate the ORH method for binary data and to illustrate sizing in a noninferiority setting. Our software package is publicly available on the Google code project hosting site for use in simulation, analysis, validation, and sizing of MRMC reader studies with binary agreement data. PMID- 26158052 TI - Impact of lesion segmentation metrics on computer-aided diagnosis/detection in breast computed tomography. AB - Evaluation of segmentation algorithms usually involves comparisons of segmentations to gold-standard delineations without regard to the ultimate medical decision-making task. We compare two segmentation evaluations methods-a Dice similarity coefficient (DSC) evaluation and a diagnostic classification task based evaluation method using lesions from breast computed tomography. In our investigation, we use results from two previously developed lesion-segmentation algorithms [a global active contour model (GAC) and a global with local aspects active contour model]. Although similar DSC values were obtained (0.80 versus 0.77), we show that the global + local active contour (GLAC) model, as compared with the GAC model, is able to yield significantly improved classification performance in terms of area under the receivers operating characteristic (ROC) curve in the task of distinguishing malignant from benign lesions. [Area under the [Formula: see text] compared to 0.63, [Formula: see text]]. This is mainly because the GLAC model yields better detailed information required in the calculation of morphological features. Based on our findings, we conclude that the DSC metric alone is not sufficient for evaluating segmentation lesions in computer-aided diagnosis tasks. PMID- 26158053 TI - Special historical reprint: An assortment of image quality indexes for radiographic film-screen combinations-can they be resolved? AB - Robert F. Wagner wrote his first SPIE paper(1) in 1972, within the first year of his joining the Bureau of Radiological Health, the precursor to the FDA's Center for Devices and Radiological Health. He had been hired to build a laboratory and develop methodologies for assessing the performance of diagnostic x-ray systems, in support of the passage of the Radiation Control for Health and Safety Act. In that first year, Bob met with leading scientists in medical imaging as well as other specialties including vision, communications, and television. He formulated a risk-benefit approach to his work, recognizing that the patient exposure associated with the creation of a medical image needed to be considered in light of the usefulness of that image. Bob's manuscript, reprinted in this special section of the Journal of Medical Imaging, provided an insightful review of the image quantification field, including modulation transfer functions, Wiener spectra, and the basis for receiver operating characteristic curves, along with a bold statement that laid the foundation for the entire field of medical imaging assessment to follow, that image quality "must be defined in terms of the task that the image is destined to perform." PMID- 26158054 TI - Evaluation of an iterative model-based reconstruction algorithm for low-tube voltage (80 kVp) computed tomography angiography. AB - The objective of this study was to investigate the improvement in diagnostic quality of an iterative model-based reconstruction (IMBR) algorithm for low-tube voltage (80-kVp) and low-tube-current in abdominal computed tomography angiography (CTA). A total of 11 patients were imaged on a 256-slice multidetector computed tomography for visualization of the aorta. For all patients, three different reconstructions from the low-tube-voltage data are generated: filtered backprojection (FBP), IMBR, and a mixture of both [Formula: see text]. To determine the diagnostic value of IMBR-based reconstructions, the image quality was assessed. With IMBR-based reconstructions, image noise could be significantly reduced, which was confirmed by a highly improved contrast-to-noise ratio. In the image quality assessment, radiologists were able to reliably detect more third-order and higher aortic branches in the IMBR reconstructions compared to FBP reconstructions. The effective dose level was, on average, 3.0 mSv for 80 kVp acquisitions. Low-tube-voltage CTAs significantly improve vascular contrast as presented by others; however, this effect in combination with IMBR enabled yet another substantial improvement of diagnostic quality. For IMBR, a significant improvement of image quality and a decreased radiation dose at low-tube-voltage can be reported. PMID- 26158055 TI - Quantitative simultaneous positron emission tomography and magnetic resonance imaging. AB - Simultaneous positron emission tomography and magnetic resonance imaging (PET-MR) is an innovative and promising imaging modality that is generating substantial interest in the medical imaging community, while offering many challenges and opportunities. In this study, we investigated whether MR surface coils need to be accounted for in PET attenuation correction. Furthermore, we integrated motion correction, attenuation correction, and point spread function modeling into a single PET reconstruction framework. We applied our reconstruction framework to in vivo animal and patient PET-MR studies. We have demonstrated that our approach greatly improved PET image quality. PMID- 26158056 TI - Noise properties and task-based evaluation of diffraction-enhanced imaging. AB - Diffraction-enhanced imaging (DEI) is an emerging x-ray imaging method that simultaneously yields x-ray attenuation and refraction images and holds great promise for soft-tissue imaging. The DEI has been mainly studied using synchrotron sources, but efforts have been made to transition the technology to more practical implementations using conventional x-ray sources. The main technical challenge of this transition lies in the relatively lower x-ray flux obtained from conventional sources, leading to photon-limited data contaminated by Poisson noise. Several issues that must be understood in order to design and optimize DEI imaging systems with respect to noise performance are addressed. Specifically, we: (a) develop equations describing the noise properties of DEI images, (b) derive the conditions under which the DEI algorithm is statistically optimal, PMID- 26158057 TI - Characterization of scatter magnitude and distribution in dedicated breast computed tomography with bowtie filters. AB - Scatter contamination of projection images in cone-beam computed tomography (CT) degrades the image quality. The use of bowtie filters in dedicated breast CT can decrease this scatter contribution. Three bowtie filter designs that compensate for one or more aspects of the beam-modifying effects due to differences in path length in a projection were studied. These designs have been investigated in terms of their ability to reduce the scatter contamination in projection images acquired in a dedicated breast CT geometry. The scatter magnitude was measured as the scatter-to-primary ratio (SPR) using experimental and Monte Carlo techniques for various breast phantom diameters and tube voltages. The results show that a 55% reduction in the center SPR value could be obtained with the bowtie filter designs. On average, the bowtie filters reduced the center SPR by approximately 18% over all breast diameters. The distribution of the scatter was calculated at a range of different locations to produce scatter distribution maps for all three bowtie filter designs. With the inclusion of the bowtie filters, the scatter distribution was more uniform for all breast diameters. The results of this study will be useful in designing scatter correction methods and understanding the benefits of bowtie filters in dedicated breast CT. PMID- 26158058 TI - Optimization of contrast-enhanced spectral mammography depending on clinical indication. AB - The objective is to optimize low-energy (LE) and high-energy (HE) exposure parameters of contrast-enhanced spectral mammography (CESM) examinations in four different clinical applications for which different levels of average glandular dose (AGD) and ratios between LE and total doses are required. The optimization was performed on a Senographe DS with a SenoBright(r) upgrade. Simulations were performed to find the optima by maximizing the contrast-to-noise ratio (CNR) on the recombined CESM image using different targeted doses and LE image quality. The linearity between iodine concentration and CNR as well as the minimal detectable iodine concentration was assessed. The image quality of the LE image was assessed on the CDMAM contrast-detail phantom. Experiments confirmed the optima found on simulation. The CNR was higher for each clinical indication than for SenoBright(r), including the screening indication for which the total AGD was 22% lower. Minimal iodine concentrations detectable in the case of a 3-mm diameter round tumor were 12.5% lower than those obtained for the same dose in the clinical routine. LE image quality satisfied EUREF acceptable limits for threshold contrast. This newly optimized set of acquisition parameters allows increased contrast detectability compared to parameters currently used without a significant loss in LE image quality. PMID- 26158059 TI - Implementing the complete beam hardening effect of the bowtie filter versus scaling beam intensities: effects on dosimetric applications in computed tomography. AB - The bowtie filter is an essential element of computed tomography scanners. Implementation of this filter in a Monte Carlo dosimetry platform can be based on Turner's method, which describes how to measure the filter thickness and relate the x-ray beam as a function of bowtie angle to the central beam. In that application, the beam hardening is accounted for by means of weighting factors that are associated to the photons according to their position (fan angle) and energy. We assessed an alternative approximation in which the photon spectrum is given a fan angle-dependent scaling factor. The aim of our investigation was to evaluate the effects on dose accuracy estimation when using the gold standard bowtie filter method versus a beam scaling approximation method. In particular, we wanted to assess the percentage dose differences between the two methods for several water thicknesses representative for different patients of different body mass index. The largest percentage differences were found for the thickest part of the bowtie filter and increased with patient size. PMID- 26158060 TI - Three-dimensional brain magnetic resonance imaging segmentation via knowledge driven decision theory. AB - Brain tissue segmentation on magnetic resonance (MR) imaging is a difficult task because of significant intensity overlap between the tissue classes. We present a new knowledge-driven decision theory (KDT) approach that incorporates prior information of the relative extents of intensity overlap between tissue class pairs for volumetric MR tissue segmentation. The proposed approach better handles intensity overlap between tissues without explicitly employing methods for removal of MR image corruptions (such as bias field). Adaptive tissue class priors are employed that combine probabilistic atlas maps with spatial contextual information obtained from Markov random fields to guide tissue segmentation. The energy function is minimized using a variational level-set-based framework, which has shown great promise for MR image analysis. We evaluate the proposed method on two well-established real MR datasets with expert ground-truth segmentations and compare our approach against existing segmentation methods. KDT has low computational complexity and shows better segmentation performance than other segmentation methods evaluated using these MR datasets. PMID- 26158061 TI - Description and classification of normal and pathological aging processes based on brain magnetic resonance imaging morphology measures. AB - We present a discrete compactness (DC) index, together with a classification scheme, based both on the size and shape features extracted from brain volumes, to determine different aging stages: healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). A set of 30 brain magnetic resonance imaging (MRI) volumes for each group was segmented and two indices were measured for several structures: three-dimensional DC and normalized volumes (NVs). The discrimination power of these indices was determined by means of the area under the curve (AUC) of the receiver operating characteristic, where the proposed compactness index showed an average AUC of 0.7 for HC versus MCI comparison, 0.9 for HC versus AD separation, and 0.75 for MCI versus AD groups. In all cases, this index outperformed the discrimination capability of the NV. Using selected features from the set of DC and NV measures, three support vector machines were optimized and validated for the pairwise separation of the three classes. Our analysis shows classification rates of up to 98.3% between HC and AD, 85% between HC and MCI, and 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indices to classify different aging stages. PMID- 26158062 TI - Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features. AB - Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the performance by leveraging the disconnected feature sets. Evaluation on the public ICPR12 mitosis dataset that has 226 mitoses annotated on 35 HPFs ([Formula: see text] magnification) by several pathologists and 15 testing HPFs yielded an [Formula: see text]-measure of 0.7345. Our approach is accurate, fast, and requires fewer computing resources compared to existent methods, making this feasible for clinical use. PMID- 26158063 TI - On the evaluation of segmentation editing tools. AB - Efficient segmentation editing tools are important components in the segmentation process, as no automatic methods exist that always generate sufficient results. Evaluating segmentation editing algorithms is challenging, because their quality depends on the user's subjective impression. So far, no established methods for an objective, comprehensive evaluation of such tools exist and, particularly, intermediate segmentation results are not taken into account. We discuss the evaluation of editing algorithms in the context of tumor segmentation in computed tomography. We propose a rating scheme to qualitatively measure the accuracy and efficiency of editing tools in user studies. In order to objectively summarize the overall quality, we propose two scores based on the subjective rating and the quantified segmentation quality over time. Finally, a simulation-based evaluation approach is discussed, which allows a more reproducible evaluation without the need for human input. This automated evaluation complements user studies, allowing a more convincing evaluation, particularly during development, where frequent user studies are not possible. The proposed methods have been used to evaluate two dedicated editing algorithms on 131 representative tumor segmentations. We show how the comparison of editing algorithms benefits from the proposed methods. Our results also show the correlation of the suggested quality score with the qualitative ratings. PMID- 26158064 TI - Robust optic nerve segmentation on clinically acquired computed tomography. AB - The optic nerve (ON) plays a critical role in many devastating pathological conditions. Segmentation of the ON has the ability to provide understanding of anatomical development and progression of diseases of the ON. Recently, methods have been proposed to segment the ON but progress toward full automation has been limited. We optimize registration and fusion methods for a new multi-atlas framework for automated segmentation of the ONs, eye globes, and muscles on clinically acquired computed tomography (CT) data. Briefly, the multi-atlas approach consists of determining a region of interest within each scan using affine registration, followed by nonrigid registration on reduced field of view atlases, and performing statistical fusion on the results. We evaluate the robustness of the approach by segmenting the ON structure in 501 clinically acquired CT scan volumes obtained from 183 subjects from a thyroid eye disease patient population. A subset of 30 scan volumes was manually labeled to assess accuracy and guide method choice. Of the 18 compared methods, the ANTS Symmetric Normalization registration and nonlocal spatial simultaneous truth and performance level estimation statistical fusion resulted in the best overall performance, resulting in a median Dice similarity coefficient of 0.77, which is comparable with inter-rater (human) reproducibility at 0.73. PMID- 26158065 TI - Interpolation-based super-resolution reconstruction: effects of slice thickness. AB - Standard clinical magnetic resonance imaging (MRI) is acquired in two-dimensions where the in-plane resolution is higher than the slice select direction. These acquisitions include axial, coronal, and sagittal planes. To date, there have been few attempts to combine the information of these three orthogonal orientations. This paper aims to take advantage of the different in-plane resolution acquired from each plane orientation and combine them into one volume in order to attain a higher resolution image. This combination of MRI data will allow the detection of smaller areas that would otherwise be missed using only one slice orientation. A comparison of slice thicknesses along with image registration is performed. The mean-squared error and peak signal-to-noise were computed for quantitative assessment. MRI and phantom scans and joint histograms were used for qualitative assessment. PMID- 26158066 TI - Computational hepatocellular carcinoma tumor grading based on cell nuclei classification. AB - Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer. HCC is graded according to the malignancy of the tissues. It is important to diagnose low-grade HCC tumors because these tissues have good prognosis. Image interpretation-based computer-aided diagnosis (CAD) systems have been developed to automate the HCC grading process. Generally, the HCC grade is determined by the characteristics of liver cell nuclei. Therefore, it is preferable that CAD systems utilize only liver cell nuclei for HCC grading. This paper proposes an automated HCC diagnosing method. In particular, it defines a pipeline-path that excludes nonliver cell nuclei in two consequent pipeline modules and utilizes the liver cell nuclear features for HCC grading. The significance of excluding the nonliver cell nuclei for HCC grading is experimentally evaluated. Four categories of liver cell nuclear features were utilized for classifying the HCC tumors. Results indicated that nuclear texture is the dominant feature for HCC grading and others contribute to increase the classification accuracy. The proposed method was employed to classify a set of regions of interest selected from HCC whole slide images into five classes and resulted in a 95.97% correct classification rate. PMID- 26158067 TI - Manually segmented template library for 8-year-old pediatric brain MRI data with 16 subcortical structures. AB - Manual segmentation of anatomy in brain MRI data taken to be the closest to the "gold standard" in quality is often used in automated registration-based segmentation paradigms for transfer of template labels onto the unlabeled MRI images. This study presents a library of template data with 16 subcortical structures in the central brain area which were manually labeled for MRI data from 22 children (8 male, [Formula: see text]). The lateral ventricle, thalamus, caudate, putamen, hippocampus, cerebellum, third vevntricle, fourth ventricle, brainstem, and corpuscallosum were segmented by two expert raters. Cross validation experiments with randomized template subset selection were conducted to test for their ability to accurately segment MRI data under an automated segmentation pipeline. A high value of the dice similarity coefficient ([Formula: see text], [Formula: see text], [Formula: see text]) and small Hausdorff distance ([Formula: see text], [Formula: see text], [Formula: see text]) of the automated segmentation against the manual labels was obtained on this template library data. Additionally, comparison with segmentation obtained from adult templates showed significant improvement in accuracy with the use of an age-matched library in this cohort. A manually delineated pediatric template library such as the one described here could provide a useful benchmark for testing segmentation algorithms. PMID- 26158068 TI - Segmenting pectoralis muscle on digital mammograms by a Markov random field maximum a posteriori model. AB - Accurate and automatic segmentation of the pectoralis muscle is essential in many breast image processing procedures, for example, in the computation of volumetric breast density from digital mammograms. Its segmentation is a difficult task due to the heterogeneity of the region, neighborhood complexities, and shape variability. The segmentation is achieved by pixel classification through a Markov random field (MRF) image model. Using the image intensity feature as observable data and local spatial information as a priori, the posterior distribution is estimated in a stochastic process. With a variable potential component in the energy function, by the maximum a posteriori (MAP) estimate of the labeling image, given the image intensity feature which is assumed to follow a Gaussian distribution, we achieved convergence properties in an appropriate sense by Metropolis sampling the posterior distribution of the selected energy function. By proposing an adjustable spatial constraint, the MRF-MAP model is able to embody the shape requirement and provide the required flexibility for the model parameter fitting process. We demonstrate that accurate and robust segmentation can be achieved for the curving-triangle-shaped pectoralis muscle in the medio-lateral-oblique (MLO) view, and the semielliptic-shaped muscle in cranio-caudal (CC) view digital mammograms. The applicable mammograms can be either "For Processing" or "For Presentation" image formats. The algorithm was developed using 56 MLO-view and 79 CC-view FFDM "For Processing" images, and quantitatively evaluated against a random selection of 122 MLO-view and 173 CC view FFDM images of both presentation intent types. PMID- 26158069 TI - Glaucoma progression detection using nonlocal Markov random field prior. AB - Glaucoma is neurodegenerative disease characterized by distinctive changes in the optic nerve head and visual field. Without treatment, glaucoma can lead to permanent blindness. Therefore, monitoring glaucoma progression is important to detect uncontrolled disease and the possible need for therapy advancement. In this context, three-dimensional (3-D) spectral domain optical coherence tomography (SD-OCT) has been commonly used in the diagnosis and management of glaucoma patients. We present a new framework for detection of glaucoma progression using 3-D SD-OCT images. In contrast to previous works that use the retinal nerve fiber layer thickness measurement provided by commercially available instruments, we consider the whole 3-D volume for change detection. To account for the spatial voxel dependency, we propose the use of the Markov random field (MRF) model as a prior for the change detection map. In order to improve the robustness of the proposed approach, a nonlocal strategy was adopted to define the MRF energy function. To accommodate the presence of false-positive detection, we used a fuzzy logic approach to classify a 3-D SD-OCT image into a "non-progressing" or "progressing" glaucoma class. We compared the diagnostic performance of the proposed framework to the existing methods of progression detection. PMID- 26158070 TI - Quantitative identification of magnetic resonance imaging features of prostate cancer response following laser ablation and radical prostatectomy. AB - Laser interstitial thermotherapy (LITT) is a relatively new focal therapy technique for the ablation of localized prostate cancer. In this study, for the first time, we are integrating ex vivo pathology and magnetic resonance imaging (MRI) to assess the imaging characteristics of prostate cancer and treatment changes following LITT. Via a unique clinical trial, which gave us the availability of ex vivo histology and pre- and post-LITT MRIs, (1) we investigated the imaging characteristics of treatment effects and residual disease, and (2) evaluated treatment-induced feature changes in the ablated area relative to the residual disease. First, a pathologist annotated the ablated area and the residual disease on the ex vivo histology. Subsequently, we transferred the annotations to the post-LITT MRI using a semi-automatic elastic registration. The pre- and post-LITT MRIs were registered and features were extracted. A scoring metric based on the change in median pre- and post-LITT feature values was introduced, which allowed us to identify the most treatment responsive features. Our results show that (1) image characteristics for treatment effects and residual disease are different, and (2) the change of feature values between pre- and post-LITT MRIs can be a quantitative biomarker for treatment response. Finally, using feature change improved discrimination between the residual disease and treatment effects. PMID- 26158071 TI - Accurate three-dimensional virtual reconstruction of surgical field using calibrated trajectories of an image-guided medical robot. AB - Brain tumor margin removal is challenging because diseased tissue is often visually indistinguishable from healthy tissue. Leaving residual tumor leads to decreased survival, and removing normal tissue causes life-long neurological deficits. Thus, a surgical robotics system with a high degree of dexterity, accurate navigation, and highly precise resection is an ideal candidate for image guided removal of fluorescently labeled brain tumor cells. To image, we developed a scanning fiber endoscope (SFE) which acquires concurrent reflectance and fluorescence wide-field images at a high resolution. This miniature flexible endoscope was affixed to the arm of a RAVEN II surgical robot providing programmable motion with feedback control using stereo-pair surveillance cameras. To verify the accuracy of the three-dimensional (3-D) reconstructed surgical field, a multimodal physical-sized model of debulked brain tumor was used to obtain the 3-D locations of residual tumor for robotic path planning to remove fluorescent cells. Such reconstruction is repeated intraoperatively during margin clean-up so the algorithm efficiency and accuracy are important to the robotically assisted surgery. Experimental results indicate that the time for creating this 3-D surface can be reduced to one-third by using known trajectories of a robot arm, and the error from the reconstructed phantom is within 0.67 mm in average compared to the model design. PMID- 26158072 TI - Evaluation of penalty design in penalized maximum-likelihood image reconstruction for lesion detection. AB - Detecting cancerous lesions is a major clinical application in emission tomography. Previously, we developed a method to design a shift-variant quadratic penalty function in penalized maximum-likelihood (PML) image reconstruction to improve the lesion detectability. We used a multiview channelized Hotelling observer (mvCHO) to assess the lesion detectability in three-dimensional images and validated the penalty design using computer simulations. In this study, we evaluate the benefit of the proposed penalty function for lesion detection using real patient data and artificial lesions. A high-count real patient dataset with no identifiable tumor inside the field of view is used as the background data. A Na-22 point source is scanned in air at variable locations and the point source data are superimposed onto the patient data as artificial lesions after being attenuated by the patient body. Independent Poisson noise is introduced to the high-count sinograms to generate 200 pairs of lesion-present and lesion-absent datasets, each mimicking a 5-min scan. Lesion detectability is assessed using a mvCHO and a human observer two-alternative forced choice (2AFC) experiment. The results show improvements in lesion detection by the proposed method compared with the conventional first-order quadratic penalty function and a total variation (TV) edge-preserving penalty function. PMID- 26158073 TI - Mechanical stability analysis of carrageenan-based polymer gel for magnetic resonance imaging liver phantom with lesion particles. AB - Medical imaging is an effective technique used to detect and prevent disease in cancer research. To optimize medical imaging, a calibration medium or phantom with tissue-mimicking properties is required. Although the feasibility of various polymer gel materials has previously been studied, the stability of the gels' properties has not been investigated. In this study, we fabricated carrageenan based polymer gel to examine the stability of its properties such as density, conductivity, permittivity, elastic modulus, and [Formula: see text] and [Formula: see text] relaxation times over six weeks. We fabricated eight samples with different carrageenan and agar concentrations and found that the density, elastic modulus, and compressive strength fluctuated with no specific pattern. The elastic modulus in sample 4 with 3 wt. % carrageenan and 1.5 wt. % agar fluctuated from 0.51 to 0.64 MPa in five weeks. The [Formula: see text] and [Formula: see text] relaxation times also varied by 23% to 29%. We believe that the fluctuation of these properties is related to the change in water content of the sample due to cycles of water expulsion and absorption in their containers. The fluctuation of the properties should be minimized to achieve accurate calibration over the shelf life of the phantom and to serve as the standard for quality assurance. Furthermore, a full liver phantom with spherical lesion particles was fabricated to demonstrate the potential for phantom production. PMID- 26158074 TI - Does preference influence performance when reading different sizes of cranial computed tomography? AB - Radiology practice is based on the implicit assumption that the preference for a particular presentation mode goes hand in hand with superior performance. The present experiment tests this assumption in what pertains to image size. Forty three radiologists were asked to identify intracranial hemorrhages on 20 cranial computed tomography scans in two image sizes, [Formula: see text] and [Formula: see text]. They were asked to indicate which size they preferred and subsequently rated each size on a continuous scale in terms of how much they liked them. The results show no correlation between the jackknife free-response receiver operating characteristic figure of merit and preference rated on a continuous scale (large image: [Formula: see text], [Formula: see text]; small images: [Formula: see text], [Formula: see text]). Similarly, there was no significant correlation between the time a radiologist took to read a case and preference rated on the continuous scale (large image: [Formula: see text], [Formula: see text]; small images: [Formula: see text], [Formula: see text]). When dividing radiologists into two groups according to their size preference, there was no significant difference in performance between groups with regard to either large or small images. The results suggest that the preference for an image size and performance with regard to it are not related. PMID- 26158075 TI - Automated speckle tracking algorithm to aid on-axis imaging in echocardiography. AB - Obtaining a "correct" view in echocardiography is a subjective process in which an operator attempts to obtain images conforming to consensus standard views. Real-time objective quantification of image alignment may assist less experienced operators, but no reliable index yet exists. We present a fully automated algorithm for detecting incorrect medial/lateral translation of an ultrasound probe by image analysis. The ability of the algorithm to distinguish optimal from sub-optimal four-chamber images was compared to that of specialists-the current "gold-standard." The orientation assessments produced by the automated algorithm correlated well with consensus visual assessments of the specialists ([Formula: see text]) and compared favourably with the correlation between individual specialists and the consensus, [Formula: see text]. Each individual specialist's assessments were within the consensus of other specialists, [Formula: see text] of the time, and the algorithm's assessments were within the consensus of specialists 85% of the time. The mean discrepancy in probe translation values between individual specialists and their consensus was [Formula: see text], and between the automated algorithm and specialists' consensus was [Formula: see text]. This technology could be incorporated into hardware to provide real-time guidance for image optimisation-a potentially valuable tool both for training and quality control. PMID- 26158076 TI - Evaluation environment for digital and analog pathology: a platform for validation studies. AB - We present a platform for designing and executing studies that compare pathologists interpreting histopathology of whole slide images (WSIs) on a computer display to pathologists interpreting glass slides on an optical microscope. eeDAP is an evaluation environment for digital and analog pathology. The key element in eeDAP is the registration of the WSI to the glass slide. Registration is accomplished through computer control of the microscope stage and a camera mounted on the microscope that acquires real-time images of the microscope field of view (FOV). Registration allows for the evaluation of the same regions of interest (ROIs) in both domains. This can reduce or eliminate disagreements that arise from pathologists interpreting different areas and focuses on the comparison of image quality. We reduced the pathologist interpretation area from an entire glass slide (10 to [Formula: see text]) to small ROIs ([Formula: see text]). We also made possible the evaluation of individual cells. We summarize eeDAP's software and hardware and provide calculations and corresponding images of the microscope FOV and the ROIs extracted from the WSIs. The eeDAP software can be downloaded from the Google code website (project: eeDAP) as a MATLAB source or as a precompiled stand-alone license-free application. PMID- 26158077 TI - On image quality metrics and the usefulness of grids in digital mammography. AB - Antiscatter grids are used in digital mammography to reduce the scattered radiation from the breast and improve image contrast. They are, however, imperfect and lead to partial absorption of primary radiation, as well as failing to absorb all scattered radiation. Nevertheless, the general consensus has been that antiscatter grids improve image quality for the majority of breast types and sizes. There is, however, inconsistency in the literature, and recent results show that a substantial image quality improvement can be achieved even for thick breasts if the grid is disposed of. The purpose of this study was to investigate if differences in the considered imaging task and experimental setup could explain the different outcomes. We estimated the dose reduction that can be achieved if the grid were to be removed as a function of breast thickness with varying geometries and experimental conditions. Image quality was quantified by the signal-difference-to-noise ratio (SDNR) measured using an aluminum (Al) filter on blocks of poly(methyl methacrylate) (PMMA), and images were acquired with and without grid at a constant exposure. We also used a theoretical model validated with Monte Carlo simulations. Both theoretically and experimentally, the main finding was that when a large [Formula: see text] Al filter was used, the SDNR values for the gridless images were overestimated up to 25% compared to the values for the small [Formula: see text] filter, and gridless imaging was superior for any PMMA thickness. For the small Al filter, gridless imaging was only superior for PMMAs thinner than 4 cm. This discrepancy can be explained by a different sensitivity to and sampling of the angular scatter spread function, depending on the size of the contrast object. The experimental differences were eliminated either by using a smaller region of interest close to the edge of the large filter or by applying a technique of scatter correction by subtracting the estimated scatter image. These results explain the different conclusions reported in the literature and show the importance of the selection of measurement methods. Since the interesting structures in mammography are below the 1-cm scale, we advocate the use of smaller contrast objects for assessment of antiscatter grid performance. PMID- 26158078 TI - Single-coil magnetic induction tomographic three-dimensional imaging. AB - Previously, magnetic induction tomography (MIT) has been considered for noncontact imaging of human tissue electrical properties. Commonly, multiple coils are used, with any one serving as the source while others detect eddy currents generated in the specimen. Here, imaging of low conductivity objects is shown feasible with a single coil acting simultaneously as source and detector, provided that the coil is repeatedly relocated while collecting coil loss data. To enable such "scanning," an analytical coil loss formula is derived in the quasistatic limit for a single coil consisting of several concentric circular wire loops, all within a common plane. Conductivity may vary arbitrarily in space, whereas permittivity and permeability are treated as uniform. The analytical form is used to build an algorithm for imaging electrical conductivity in human tissues. A practical device operating at 12.5 MHz is described and used in a clinical trial that "scans" the region between the scapulae while collecting coil loss data. Inversion of data leads to electrical conductivity distribution images for the thoracic spinal column which are the first of their kind to correctly distinguish such basic features as size and depth of spinal canal, as well as size, depth, and spacing of transverse spinal processes. PMID- 26158079 TI - Assessment of natural enamel lesions with optical coherence tomography in comparison with microfocus x-ray computed tomography. AB - A technology to characterize early enamel lesions is needed in dentistry. Optical coherence tomography (OCT) is a noninvasive method that provides high-resolution cross-sectional images. The aim of this study is to compare OCT with microfocus x ray computed tomography ([Formula: see text]) for assessment of natural enamel lesions in vitro. Ten human teeth with visible white spot-like changes on the enamel smooth surface and no cavitation (ICDAS code 2) were subjected to imaging by MUCT (SMX-100CT, Shimadzu) and 1300-nm swept-source OCT (Dental SS-OCT, Panasonic Health Care). In [Formula: see text], the lesions appeared as radiolucent dark areas, while in SS-OCT, they appeared as areas of increased signal intensity beneath the surface. An SS-OCT attenuation coefficient based on Beer-Lambert law could discriminate lesions from sound enamel. Lesion depth ranged from 175 to [Formula: see text] in SS-OCT. A correlation between [Formula: see text] and SS-OCT was found regarding lesion depth ([Formula: see text], [Formula: see text]) and also surface layer thickness ([Formula: see text], [Formula: see text]). The images obtained clinically in real time using the dental SS-OCT system are suitable for the assessment of natural subsurface lesions and their surface layer, providing comparable images to a laboratory high resolution [Formula: see text] without the use of x-ray. PMID- 26158080 TI - Etiology-based classification of brain white matter hyperintensity on magnetic resonance imaging. AB - Brain white matter lesions found upon magnetic resonance imaging are often observed in psychiatric or neurological patients. Individuals with these lesions present a more significant cognitive impairment when compared with individuals without them. We propose a computerized method to distinguish tissue containing white matter lesions of different etiologies (e.g., demyelinating or ischemic) using texture-based classifiers. Texture attributes were extracted from manually selected regions of interest and used to train and test supervised classifiers. Experiments were conducted to evaluate texture attribute discrimination and classifiers' performances. The most discriminating texture attributes were obtained from the gray-level histogram and from the co-occurrence matrix. The best classifier was the support vector machine, which achieved an accuracy of 87.9% in distinguishing lesions with different etiologies and an accuracy of 99.29% in distinguishing normal white matter from white matter lesions. PMID- 26158081 TI - Structured learning algorithm for detection of nonobstructive and obstructive coronary plaque lesions from computed tomography angiography. AB - Visual identification of coronary arterial lesion from three-dimensional coronary computed tomography angiography (CTA) remains challenging. We aimed to develop a robust automated algorithm for computer detection of coronary artery lesions by machine learning techniques. A structured learning technique is proposed to detect all coronary arterial lesions with stenosis [Formula: see text]. Our algorithm consists of two stages: (1) two independent base decisions indicating the existence of lesions in each arterial segment and (b) the final decision made by combining the base decisions. One of the base decisions is the support vector machine (SVM) based learning algorithm, which divides each artery into small volume patches and integrates several quantitative geometric and shape features for arterial lesions in each small volume patch by SVM algorithm. The other base decision is the formula-based analytic method. The final decision in the first stage applies SVM-based decision fusion to combine the two base decisions in the second stage. The proposed algorithm was applied to 42 CTA patient datasets, acquired with dual-source CT, where 21 datasets had 45 lesions with stenosis [Formula: see text]. Visual identification of lesions with stenosis [Formula: see text] by three expert readers, using consensus reading, was considered as a reference standard. Our method performed with high sensitivity (93%), specificity (95%), and accuracy (94%), with receiver operator characteristic area under the curve of 0.94. The proposed algorithm shows promising results in the automated detection of obstructive and nonobstructive lesions from CTA. PMID- 26158082 TI - Automated brain computed tomographic densitometry of early ischemic changes in acute stroke. AB - The Alberta Stroke Program Early CT score (ASPECTS) scoring method is frequently used for quantifying early ischemic changes (EICs) in patients with acute ischemic stroke in clinical studies. Varying interobserver agreement has been reported, however, with limited agreement. Therefore, our goal was to develop and evaluate an automated brain densitometric method. It divides CT scans of the brain into ASPECTS regions using atlas-based segmentation. EICs are quantified by comparing the brain density between contralateral sides. This method was optimized and validated using CT data from 10 and 63 patients, respectively. The automated method was validated against manual ASPECTS, stroke severity at baseline and clinical outcome after 7 to 10 days (NIH Stroke Scale, NIHSS) and 3 months (modified Rankin Scale). Manual and automated ASPECTS showed similar and statistically significant correlations with baseline NIHSS ([Formula: see text] and [Formula: see text], respectively) and with follow-up mRS ([Formula: see text] and [Formula: see text]), except for the follow-up NIHSS. Agreement between automated and consensus ASPECTS reading was similar to the interobserver agreement of manual ASPECTS (differences [Formula: see text] point in 73% of cases). The automated ASPECTS method could, therefore, be used as a supplementary tool to assist manual scoring. PMID- 26158083 TI - Consistency-based rectification of nonrigid registrations. AB - We present a technique to rectify nonrigid registrations by improving their group wise consistency, which is a widely used unsupervised measure to assess pair-wise registration quality. While pair-wise registration methods cannot guarantee any group-wise consistency, group-wise approaches typically enforce perfect consistency by registering all images to a common reference. However, errors in individual registrations to the reference then propagate, distorting the mean and accumulating in the pair-wise registrations inferred via the reference. Furthermore, the assumption that perfect correspondences exist is not always true, e.g., for interpatient registration. The proposed consistency-based registration rectification (CBRR) method addresses these issues by minimizing the group-wise inconsistency of all pair-wise registrations using a regularized least squares algorithm. The regularization controls the adherence to the original registration, which is additionally weighted by the local postregistration similarity. This allows CBRR to adaptively improve consistency while locally preserving accurate pair-wise registrations. We show that the resulting registrations are not only more consistent, but also have lower average transformation error when compared to known transformations in simulated data. On clinical data, we show improvements of up to 50% target registration error in breathing motion estimation from four-dimensional MRI and improvements in atlas based segmentation quality of up to 65% in terms of mean surface distance in three-dimensional (3-D) CT. Such improvement was observed consistently using different registration algorithms, dimensionality (two-dimensional/3-D), and modalities (MRI/CT). PMID- 26158084 TI - Automated segmentation of geographic atrophy in fundus autofluorescence images using supervised pixel classification. AB - Geographic atrophy (GA) is a manifestation of the advanced or late stage of age related macular degeneration (AMD). AMD is the leading cause of blindness in people over the age of 65 in the western world. The purpose of this study is to develop a fully automated supervised pixel classification approach for segmenting GA, including uni- and multifocal patches in fundus autofluorescene (FAF) images. The image features include region-wise intensity measures, gray-level co occurrence matrix measures, and Gaussian filter banks. A [Formula: see text] nearest-neighbor pixel classifier is applied to obtain a GA probability map, representing the likelihood that the image pixel belongs to GA. Sixteen randomly chosen FAF images were obtained from 16 subjects with GA. The algorithm-defined GA regions are compared with manual delineation performed by a certified image reading center grader. Eight-fold cross-validation is applied to evaluate the algorithm performance. The mean overlap ratio (OR), area correlation (Pearson's [Formula: see text]), accuracy (ACC), true positive rate (TPR), specificity (SPC), positive predictive value (PPV), and false discovery rate (FDR) between the algorithm- and manually defined GA regions are [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text], respectively. PMID- 26158085 TI - Mammographic density measurements are not affected by mammography system. AB - Mammographic density (MD) is a significant risk factor for breast cancer and has been shown to reduce the sensitivity of mammography screening. Knowledge of a woman's density can be used to predict her risk of developing breast cancer and personalize her imaging pathway. However, measurement of breast density has proven to be troublesome with wide variations in density recorded using radiologists' visual Breast Imaging Reporting and Data System (BIRADS). Several automated methods for assessing breast density have been proposed, each with their own source of measurement error. The use of differing mammographic imaging systems further complicates MD measurement, especially for the same women imaged over time. The purpose of this study was to investigate whether having a mammogram on differing manufacturer's equipment affects a woman's MD measurement. Raw mammographic images were acquired on two mammography imaging systems (General Electric and Hologic) one year apart and processed using VolparaDensityTM to obtain the Volpara Density Grade (VDG) and average volumetric breast density percentage (AvBD%). Visual BIRADS scores were also obtained from 20 expert readers. BIRADS scores for both systems showed strong positive correlation ([Formula: see text]; [Formula: see text]), while the VDG ([Formula: see text]; [Formula: see text]) and AvBD% ([Formula: see text]; [Formula: see text]) showed stronger positive correlations. Substantial agreement was shown between the systems for BIRADS ([Formula: see text]; [Formula: see text]), however, the systems demonstrated an almost perfect agreement for VDG ([Formula: see text]; [Formula: see text]). PMID- 26158086 TI - Implementation of a channelized Hotelling observer model to assess image quality of x-ray angiography systems. AB - Evaluation of flat-panel angiography equipment through conventional image quality metrics is limited by the scope of standard spatial-domain image quality metric(s), such as contrast-to-noise ratio and spatial resolution, or by restricted access to appropriate data to calculate Fourier domain measurements, such as modulation transfer function, noise power spectrum, and detective quantum efficiency. Observer models have been shown capable of overcoming these limitations and are able to comprehensively evaluate medical-imaging systems. We present a spatial domain-based channelized Hotelling observer model to calculate the detectability index (DI) of our different sized disks and compare the performance of different imaging conditions and angiography systems. When appropriate, changes in DIs were compared to expectations based on the classical Rose model of signal detection to assess linearity of the model with quantum signal-to-noise ratio (SNR) theory. For these experiments, the estimated uncertainty of the DIs was less than 3%, allowing for precise comparison of imaging systems or conditions. For most experimental variables, DI changes were linear with expectations based on quantum SNR theory. DIs calculated for the smallest objects demonstrated nonlinearity with quantum SNR theory due to system blur. Two angiography systems with different detector element sizes were shown to perform similarly across the majority of the detection tasks. PMID- 26158087 TI - Parameter estimation of atherosclerotic tissue optical properties from three dimensional intravascular optical coherence tomography. AB - We developed robust, three-dimensional methods, as opposed to traditional A-line analysis, for estimating the optical properties of calcified, fibrotic, and lipid atherosclerotic plaques from in vivo coronary artery intravascular optical coherence tomography clinical pullbacks. We estimated attenuation [Formula: see text] and backscattered intensity [Formula: see text] from small volumes of interest annotated by experts in 35 pullbacks. Some results were as follows: noise reduction filtering was desirable, parallel line (PL) methods outperformed individual line methods, root mean square error was the best goodness-of-fit, and [Formula: see text]-trimmed PL ([Formula: see text]-T-PL) was the best overall method. Estimates of [Formula: see text] were calcified ([Formula: see text]), fibrotic ([Formula: see text]), and lipid ([Formula: see text]), similar to those in the literature, and tissue classification from optical properties alone was promising. PMID- 26158088 TI - Experimental quantification of the tactile spatial responsivity of human cornea. AB - We present the first experimental quantification of the tactile spatial responsivity of the cornea and we teach a subject to recognize spatial tactile shapes that are stimulated on their cornea. PMID- 26158089 TI - Multipurpose nonlinear optical imaging system for in vivo and ex vivo multimodal histology. AB - We report on a flexible multipurpose nonlinear microscopic imaging system based on a femtosecond excitation source and a photonic crystal fiber with multiple miniaturized time-correlated single-photon counting detectors. The system provides the simultaneous acquisition of e.g., two-photon autofluorescence, second-harmonic generation, and coherent anti-Stokes Raman scattering images. Its flexible scan head permits ex vivo biological imaging with subcellular resolution such as rapid biopsy examination during surgery as well as imaging on small as well as large animals. Above all, such an arrangement perfectly matches the needs for the clinical investigation of human skin in vivo where knowledge about the distribution of endogenous fluorophores, second-harmonic generation-active collagen as well as nonfluorescent lipids is of high interest. PMID- 26158090 TI - Block selective redaction for minimizing loss during de-identification of burned in text in irreversibly compressed JPEG medical images. AB - Deidentification of medical images requires attention to both header information as well as the pixel data itself, in which burned-in text may be present. If the pixel data to be deidentified is stored in a compressed form, traditionally it is decompressed, identifying text is redacted, and if necessary, pixel data are recompressed. Decompression without recompression may result in images of excessive or intractable size. Recompression with an irreversible scheme is undesirable because it may cause additional loss in the diagnostically relevant regions of the images. The irreversible (lossy) JPEG compression scheme works on small blocks of the image independently, hence, redaction can selectively be confined only to those blocks containing identifying text, leaving all other blocks unchanged. An open source implementation of selective redaction and a demonstration of its applicability to multiframe color ultrasound images is described. The process can be applied either to standalone JPEG images or JPEG bit streams encapsulated in other formats, which in the case of medical images, is usually DICOM. PMID- 26158093 TI - Introduction to the LUNGx Challenge. PMID- 26158091 TI - Resolution enhancement in medical ultrasound imaging. AB - Image resolution enhancement is a problem of considerable interest in all medical imaging modalities. Unlike general purpose imaging or video processing, for a very long time, medical image resolution enhancement has been based on optimization of the imaging devices. Although some recent works purport to deal with image postprocessing, much remains to be done regarding medical image enhancement via postprocessing, especially in ultrasound imaging. We face a resolution improvement issue in the case of medical ultrasound imaging. We propose to investigate this problem using multidimensional autoregressive (AR) models. Noting that the estimation of the envelope of an ultrasound radio frequency (RF) signal is very similar to the estimation of classical Fourier based power spectrum estimation, we theoretically show that a domain change and a multidimensional AR model can be used to achieve super-resolution in ultrasound imaging provided the order is estimated correctly. Here, this is done by means of a technique that simultaneously estimates the order and the parameters of a multidimensional model using relevant regression matrix factorization. Doing so, the proposed method specifically fits ultrasound imaging and provides an estimated envelope. Moreover, an expression that links the theoretical image resolution to both the image acquisition features (such as the point spread function) and a postprocessing feature (the AR model) order is derived. The overall contribution of this work is threefold. First, it allows for automatic resolution improvement. Through a simple model and without any specific manual algorithmic parameter tuning, as is used in common methods, the proposed technique simply and exclusively uses the ultrasound RF signal as input and provides the improved B-mode as output. Second, it allows for the a priori prediction of the improvement in resolution via the knowledge of the parametric model order before actual processing. Finally, to achieve the previous goal, while classical parametric methods would first estimate the model order and then the model parameters, our approach estimates the model parameters and the order simultaneously. The effectiveness of the methodology is validated using two dimensional synthetic and in vivo data. We show that, compared to other techniques, our method provides better results from a qualitative and a quantitative viewpoint. PMID- 26158094 TI - LUNGx Challenge for computerized lung nodule classification: reflections and lessons learned. PMID- 26158095 TI - Evaluation of position-estimation methods applied to CZT-based photon-counting detectors for dedicated breast CT. AB - Semiconductor photon-counting detectors based on high atomic number, high density materials [cadmium zinc telluride (CZT)/cadmium telluride (CdTe)] for x-ray computed tomography (CT) provide advantages over conventional energy-integrating detectors, including reduced electronic and Swank noise, wider dynamic range, capability of spectral CT, and improved signal-to-noise ratio. Certain CT applications require high spatial resolution. In breast CT, for example, visualization of microcalcifications and assessment of tumor microvasculature after contrast enhancement require resolution on the order of [Formula: see text]. A straightforward approach to increasing spatial resolution of pixellated CZT-based radiation detectors by merely decreasing the pixel size leads to two problems: (1) fabricating circuitry with small pixels becomes costly and (2) inter-pixel charge spreading can obviate any improvement in spatial resolution. We have used computer simulations to investigate position estimation algorithms that utilize charge sharing to achieve subpixel position resolution. To study these algorithms, we model a simple detector geometry with a [Formula: see text] array of [Formula: see text] pixels, and use a conditional probability function to model charge transport in CZT. We used COMSOL finite element method software to map the distribution of charge pulses and the Monte Carlo package PENELOPE for simulating fluorescent radiation. Performance of two x-ray interaction position estimation algorithms was evaluated: the method of maximum-likelihood estimation and a fast, practical algorithm that can be implemented in a readout application specific integrated circuit and allows for identification of a quadrant of the pixel in which the interaction occurred. Both methods demonstrate good subpixel resolution; however, their actual efficiency is limited by the presence of fluorescent [Formula: see text]-escape photons. Current experimental breast CT systems typically use detectors with a pixel size of [Formula: see text], with [Formula: see text] binning during the acquisition giving an effective pixel size of [Formula: see text]. Thus, it would be expected that the position estimate accuracy reported in this study would improve detection and visualization of microcalcifications as compared to that with conventional detectors. PMID- 26158096 TI - Automatic segmentation of high- and low-field knee MRIs using knee image quantification with data from the osteoarthritis initiative. AB - Clinical studies including thousands of magnetic resonance imaging (MRI) scans offer potential for pathogenesis research in osteoarthritis. However, comprehensive quantification of all bone, cartilage, and meniscus compartments is challenging. We propose a segmentation framework for fully automatic segmentation of knee MRI. The framework combines multiatlas rigid registration with voxel classification and was trained on manual segmentations with varying configurations of bones, cartilages, and menisci. The validation included high- and low-field knee MRI cohorts from the Center for Clinical and Basic Research, the osteoarthritis initiative (QAI), and the segmentation of knee images10 (SKI10) challenge. In total, 1907 knee MRIs were segmented during the evaluation. No segmentations were excluded. Our resulting OAI cartilage volume scores are available upon request. The precision and accuracy performances matched manual reader re-segmentation well. The cartilage volume scan-rescan precision was 4.9% (RMS CV). The Dice volume overlaps in the medial/lateral tibial/femoral cartilage compartments were 0.80 to 0.87. The correlations with volumes from independent methods were between 0.90 and 0.96 on the OAI scans. Thus, the framework demonstrated precision and accuracy comparable to manual segmentations. Finally, our method placed second for cartilage segmentation in the SKI10 challenge. The comprehensive validation suggested that automatic segmentation is appropriate for cohorts with thousands of scans. PMID- 26158097 TI - Quantitative analysis of rib kinematics based on dynamic chest bone images: preliminary results. AB - An image-processing technique for separating bones from soft tissue in static chest radiographs has been developed. The present study was performed to evaluate the usefulness of dynamic bone images in quantitative analysis of rib movement. Dynamic chest radiographs of 16 patients were obtained using a dynamic flat-panel detector and processed to create bone images by using commercial software (Clear Read BS, Riverain Technologies). Velocity vectors were measured in local areas on the dynamic images, which formed a map. The velocity maps obtained with bone and original images for scoliosis and normal cases were compared to assess the advantages of bone images. With dynamic bone images, we were able to quantify and distinguish movements of ribs from those of other lung structures accurately. Limited rib movements of scoliosis patients appeared as a reduced rib velocity field, resulting in an asymmetrical distribution of rib movement. Vector maps in all normal cases exhibited left/right symmetric distributions of the velocity field, whereas those in abnormal cases showed asymmetric distributions because of locally limited rib movements. Dynamic bone images were useful for accurate quantitative analysis of rib movements. The present method has a potential for an additional functional examination in chest radiography. PMID- 26158098 TI - Synthesis of intensity gradient and texture information for efficient three dimensional segmentation of medical volumes. AB - We propose a framework that efficiently employs intensity, gradient, and textural features for three-dimensional (3-D) segmentation of medical (MRI/CT) volumes. Our methodology commences by determining the magnitude of intensity variations across the input volume using a 3-D gradient detection scheme. The resultant gradient volume is utilized in a dynamic volume growing/formation process that is initiated in voxel locations with small gradient magnitudes and is concluded at sites with large gradient magnitudes, yielding a map comprising an initial set of partitions (or subvolumes). This partition map is combined with an entropy-based texture descriptor along with intensity and gradient attributes in a multivariate analysis-based volume merging procedure that fuses subvolumes with similar characteristics to yield a final/refined segmentation output. Additionally, a semiautomated version of the aforestated algorithm that allows a user to interactively segment a desired subvolume of interest as opposed to the entire volume is also discussed. Our approach was tested on several MRI and CT datasets and the results show favorable performance in comparison to the state-of-the-art ITK-SNAP technique. PMID- 26158099 TI - Reconstruction of four-dimensional computed tomography lung images by applying spatial and temporal anatomical constraints using a Bayesian model. AB - Current four-dimensional computed tomography (4-D CT) lung image reconstruction methods rely on respiratory gating, such as surrogate, to sort the large number of axial images captured during multiple breathing cycles into serial three dimensional CT images of different respiratory phases. Such sorting methods may be subject to external surrogate signal noises due to poor reproducibility of breathing cycles. New image-matching-based reconstruction algorithms refine the 4 D CT reconstruction by matching neighboring image slices, and they generally work better for the cine mode of 4-D CT acquisition than the helical mode due to different table positions of axial images in the helical mode. We propose a Bayesian model (BM) based automated 4-D CT lung image reconstruction for helical mode scans. BM allows for applying new spatial and temporal anatomical constraints in the optimization procedure. Using an iterative optimization procedure, each axial image is assigned to a respiratory phase to make sure the anatomical structures are spatially and temporally smooth based on the BM framework. In experiments, we visually and quantitatively compared the results of the proposed BM-based 4-D CT reconstruction with the respiratory surrogate and the normalized cross-correlation based image matching method using both simulated and actual 4-D patient scans. The results indicated that the proposed algorithm yielded more accurate reconstruction and fewer artifacts in the 4-D CT image series. PMID- 26158100 TI - Noise distribution and denoising of current density images. AB - Current density imaging (CDI) is a magnetic resonance (MR) imaging technique that could be used to study current pathways inside the tissue. The current distribution is measured indirectly as phase changes. The inherent noise in the MR imaging technique degrades the accuracy of phase measurements leading to imprecise current variations. The outcome can be affected significantly, especially at a low signal-to-noise ratio (SNR). We have shown the residual noise distribution of the phase to be Gaussian-like and the noise in CDI images approximated as a Gaussian. This finding matches experimental results. We further investigated this finding by performing comparative analysis with denoising techniques, using two CDI datasets with two different currents (20 and 45 mA). We found that the block-matching and three-dimensional (BM3D) technique outperforms other techniques when applied on current density ([Formula: see text]). The minimum gain in noise power by BM3D applied to [Formula: see text] compared with the next best technique in the analysis was found to be around 2 dB per pixel. We characterize the noise profile in CDI images and provide insights on the performance of different denoising techniques when applied at two different stages of current density reconstruction. PMID- 26158101 TI - Semiautomated hybrid algorithm for estimation of three-dimensional liver surface in CT using dynamic cellular automata and level-sets. AB - Liver segmentation continues to remain a major challenge, largely due to its intense complexity with surrounding anatomical structures (stomach, kidney, and heart), high noise level and lack of contrast in pathological computed tomography (CT) data. We present an approach to reconstructing the liver surface in low contrast CT. The main contributions are: (1) a stochastic resonance-based methodology in discrete cosine transform domain is developed to enhance the contrast of pathological liver images, (2) a new formulation is proposed to prevent the object boundary, resulting from the cellular automata method, from leaking into the surrounding areas of similar intensity, and (3) a level-set method is suggested to generate intermediate segmentation contours from two segmented slices distantly located in a subject sequence. We have tested the algorithm on real datasets obtained from two sources, Hamad General Hospital and medical image computing and computer-assisted interventions grand challenge workshop. Various parameters in the algorithm, such as [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text], play imperative roles, thus their values are precisely selected. Both qualitative and quantitative evaluation performed on liver data show promising segmentation accuracy when compared with ground truth data reflecting the potential of the proposed method. PMID- 26158102 TI - Fully automatic initialization of two-dimensional-three-dimensional medical image registration using hybrid classifier. AB - X-ray video fluoroscopy along with two-dimensional-three-dimensional (2D-3D) registration techniques is widely used to study joints in vivo kinematic behaviors. These techniques, however, are generally very sensitive to the initial alignment of the 3-D model. We present an automatic initialization method for 2D 3D registration of medical images. The contour of the knee bone or implant was first automatically extracted from a 2-D x-ray image. Shape descriptors were calculated by normalized elliptical Fourier descriptors to represent the contour shape. The optimal pose was then determined by a hybrid classifier combining [Formula: see text]-nearest neighbors and support vector machine. The feasibility of the method was first validated on computer synthesized images, with 100% successful estimation for the femur and tibia implants, 92% for the femur and 95% for the tibia. The method was further validated on fluoroscopic x-ray images with all the poses of the testing cases successfully estimated. Finally, the method was evaluated as an initialization of a feature-based 2D-3D registration. The initialized and uninitialized registrations had success rates of 100% and 50%, respectively. The proposed method can be easily utilized for 2D-3D image registration on various medical objects and imaging modalities. PMID- 26158103 TI - Reduction of acquisition time in the intersection profile method for four dimensional magnetic resonance imaging reconstruction of thoracoabdominal organs. AB - We have previously proposed an intersection profile method for reconstructing four-dimensional (4-D) magnetic resonance imaging (MRI) consisting of one breathing cycle of the thoracoabdominal region. This method captures a set of temporal sequence images in a proper sagittal plane and sets of temporal sequence images in continuous coronal slices. The former set is used as a navigator slice and the latter sets are used as data slices. A 4-D MRI is reconstructed by synchronizing the respiratory pattern found in the navigator slice and the data slices. We propose a prospective method to reduce the acquisition time for data slices. During data slice acquisition, the synchronization process between the respiratory pattern found in the navigator slice and one data slice is monitored in real time. Data acquisition will be terminated and moved to the next data slice based on a threshold value. We used 14 data sets (seven patients with certain pulmonary disease and seven healthy volunteers) previously obtained for the original intersection profile method for a simulation using the proposed method to evaluate the time reduction and impact on image quality. Each of the data set was tested using three different threshold values and the acquisition time can be reduced up to 75%. Although the quantitative evaluation of image quality was slightly worse than that by the conventional method, the difference based on the visual inspection was subtle to human eyes. PMID- 26158104 TI - Automatic correction of dental artifacts in PET/MRI. AB - A challenge when using current magnetic resonance (MR)-based attenuation correction in positron emission tomography/MR imaging (PET/MRI) is that the MRIs can have a signal void around the dental fillings that is segmented as artificial air-regions in the attenuation map. For artifacts connected to the background, we propose an extension to an existing active contour algorithm to delineate the outer contour using the nonattenuation corrected PET image and the original attenuation map. We propose a combination of two different methods for differentiating the artifacts within the body from the anatomical air-regions by first using a template of artifact regions, and second, representing the artifact regions with a combination of active shape models and k-nearest-neighbors. The accuracy of the combined method has been evaluated using 25 [Formula: see text] fluorodeoxyglucose PET/MR patients. Results showed that the approach was able to correct an average of [Formula: see text] of the artifact areas. PMID- 26158105 TI - Parenchymal texture analysis in digital mammography: robust texture feature identification and equivalence across devices. AB - An analytical framework is presented for evaluating the equivalence of parenchymal texture features across different full-field digital mammography (FFDM) systems using a physical breast phantom. Phantom images (FOR PROCESSING) are acquired from three FFDM systems using their automated exposure control setting. A panel of texture features, including gray-level histogram, co occurrence, run length, and structural descriptors, are extracted. To identify features that are robust across imaging systems, a series of equivalence tests are performed on the feature distributions, in which the extent of their intersystem variation is compared to their intrasystem variation via the Hodges Lehmann test statistic. Overall, histogram and structural features tend to be most robust across all systems, and certain features, such as edge enhancement, tend to be more robust to intergenerational differences between detectors of a single vendor than to intervendor differences. Texture features extracted from larger regions of interest (i.e., [Formula: see text]) and with a larger offset length (i.e., [Formula: see text]), when applicable, also appear to be more robust across imaging systems. This framework and observations from our experiments may benefit applications utilizing mammographic texture analysis on images acquired in multivendor settings, such as in multicenter studies of computer-aided detection and breast cancer risk assessment. PMID- 26158106 TI - Preliminary assessment of dispersion versus absorption analysis of high spectral and spatial resolution magnetic resonance images in the diagnosis of breast cancer. AB - Water resonance lineshapes observed in breast lesions imaged with high spectral and spatial resolution (HiSS) magnetic resonance imaging have been shown to contain diagnostically useful non-Lorentzian components. The purpose of this work is to update a previous method of breast lesion diagnosis by including phase corrected absorption and dispersion spectra. This update includes information about the shape of the complex water resonance, which could improve the performance of a computer-aided diagnosis breast lesion classification scheme. The non-Lorentzian characteristics observed in complex breast lesion water resonance spectra are characterized by comparing a plot of the real versus imaginary components of the spectrum to that of a perfect complex Lorentzian spectrum, a "dispersion versus absorption" (DISPA) analysis technique. Distortion in the shape of the observed spectra indicates underlying physiologic changes, which have been shown to be correlated with malignancy. These spectral shape distortions in each lesion voxel are quantified by summing the deviations in DISPA radius from an ideal complex Lorentzian spectrum over all Fourier components, yielding a "total radial difference" (TRD). We limited our analysis to those voxels in each lesion with the largest TRD. The number of voxels considered was dependent on the lesion size. The TRD was used to classify voxels from 15 malignant and 8 benign lesions ([Formula: see text] voxels after voxel elimination). Lesion discrimination performance was evaluated for both the average and variance of the TRD within each lesion. Area under the receiver operating characteristic curve (ROC AUC) was used to assess both the voxel- and lesion-based discrimination methods in the task of distinguishing between malignant and benign. In the task of distinguishing voxels from malignant and benign lesions, TRD yielded an AUC of 0.89 (95% confidence interval [0.84, 0.91]). In the task of distinguishing malignant from benign lesions, the average radial difference yielded an AUC of 0.90 (95% confidence interval [0.71, 1.00]) and the variance in the radial difference yielded an AUC of 0.84 (95% confidence interval [0.61, 0.99]). We have applied the DISPA spectroscopic analysis method to HiSS data in order to identify and quantify voxels in breast lesions displaying non-Lorentzian characteristics. We have shown that a breast lesion classification scheme based on the absorption and dispersion spectral data obtained from HiSS acquisitions may outperform a similar classifier based on single off-peak component analysis, as it uses shape details of the entire spectrum instead of the magnitude at a single spectral location. PMID- 26158107 TI - Neuromorphometry of primary brain tumors by magnetic resonance imaging. AB - Magnetic resonance imaging is a technique for the diagnosis and classification of brain tumors. Discrete compactness is a morphological feature of two-dimensional and three-dimensional objects. This measure determines the compactness of a discretized object depending on the sum of the areas of the connected voxels and has been used for understanding the morphology of nonbrain tumors. We hypothesized that regarding brain tumors, we may improve the malignancy grade classification. We analyzed the values in 20 patients with different subtypes of primary brain tumors: astrocytoma, oligodendroglioma, and glioblastoma multiforme subdivided into the contrast-enhanced and the necrotic tumor regions. The preliminary results show an inverse relationship between the compactness value and the malignancy grade of gliomas. Astrocytomas exhibit a mean of [Formula: see text], whereas oligodendrogliomas exhibit a mean of [Formula: see text]. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of [Formula: see text], and the necrotic region presented a mean of [Formula: see text]. However, the volume and area of the enclosing surface did not show a relationship with the malignancy grade of the gliomas. Discrete compactness appears to be a stable characteristic between primary brain tumors of different malignancy grades, because similar values were obtained from different patients with the same type of tumor. PMID- 26158108 TI - Texture analysis of images using a two-dimensional fast time-frequency transform. AB - The two-dimensional S-transform (ST-2D) is a time-frequency representation that is widely used in medical image processing but prohibitive in both storage and computation time. The high computation time required for generating local spectrum discourages the use of ST-2D for analyzing textures in medical images. A two-dimensional fast time-frequency transform (FTFT-2D) for computing the local spectrum instantaneously and accurately is proposed. It can also be used to compute the complete redundant discrete ST-2D output, if needed. It reduces the storage requirement by generating a compressed form of the ST-2D. In addition, the memory efficient and adaptive nature of the FTFT-2D make it suitable for user specific requirements. PMID- 26158109 TI - Radiological technologists' performance for the detection of malignant microcalcifications in digital mammograms without and with a computer-aided detection system. AB - The aim of this study was to investigate the diagnostic performance of radiological technologists (RTs) in the detection of malignant microcalcifications and to evaluate how much computer-aided detection (CADe) improved their performances compared with those by expert breast radiologists (BRs). Six board-certified breast RTs and four board-certified BRs participated in a free-response receiver operating characteristic observer study. The dataset consisted of 75 cases (25 malignant, 25 benign, and 25 normal cases) of digital mammograms, selected from the digital database for screening mammography provided by the University of South Florida. Average figure of merit (FOM) of the RTs' performances was statistically analyzed using jack-knife free-response receiver operating characteristic and compared with that of expert BRs. The detection performance of RTs was significantly improved by using CADe; average sensitivity was increased from 46.7% to 56.7%, with a decrease in the average number of false positives per case from 0.19 to 0.13. Detection accuracy of an average FOM was improved from 0.680 to 0.816 ([Formula: see text]) and the difference in FOMs between RTs and radiologists failed to reach statistical significance. RTs' performances for the identification of malignant microcalcifications on digital mammography were sufficiently high and comparable to those of radiologists by using CADe. PMID- 26158110 TI - Parametric ultrasound and fluoroscopy image fusion for guidance of left ventricle lead placement in cardiac resynchronization therapy. AB - Recent studies show that the response rate to cardiac resynchronization therapy (CRT) could be improved if the left ventricle (LV) is paced at the site of the latest mechanical activation, but away from the myocardial scar. A prototype system for CRT lead placement guidance that combines LV functional information from ultrasound with live x-ray fluoroscopy was developed. Two mean anatomical models, each containing LV epi-, LV endo- and right ventricle endocardial surfaces, were computed from a database of 33 heart failure patients as a substitute for a patient-specific model. The sphericity index was used to divide the observed population into two groups. The distance between the mean and the patient-specific models was determined using a signed distance field metric (reported in mm). The average error values for LV epicardium were [Formula: see text] and for LV endocardium were [Formula: see text]. The validity of using average LV models for a CRT procedure was tested by simulating coronary vein selection in a group of 15 CRT candidates. The probability of selecting the same coronary branch, when basing the selection on the average model compared to a patient-specific model, was estimated to be [Formula: see text]. This was found to be clinically acceptable. PMID- 26158111 TI - Three-dimensional nonrigid landmark-based magnetic resonance to transrectal ultrasound registration for image-guided prostate biopsy. AB - Registration of three-dimensional (3-D) magnetic resonance (MR) to 3-D transrectal ultrasound (TRUS) prostate images is an important step in the planning and guidance of 3-D TRUS guided prostate biopsy. In order to accurately and efficiently perform the registration, a nonrigid landmark-based registration method is required to account for the different deformations of the prostate when using these two modalities. We describe a nonrigid landmark-based method for registration of 3-D TRUS to MR prostate images. The landmark-based registration method first makes use of an initial rigid registration of 3-D MR to 3-D TRUS images using six manually placed approximately corresponding landmarks in each image. Following manual initialization, the two prostate surfaces are segmented from 3-D MR and TRUS images and then nonrigidly registered using the following steps: (1) rotationally reslicing corresponding segmented prostate surfaces from both 3-D MR and TRUS images around a specified axis, (2) an approach to find point correspondences on the surfaces of the segmented surfaces, and (3) deformation of the surface of the prostate in the MR image to match the surface of the prostate in the 3-D TRUS image and the interior using a thin-plate spline algorithm. The registration accuracy was evaluated using 17 patient prostate MR and 3-D TRUS images by measuring the target registration error (TRE). Experimental results showed that the proposed method yielded an overall mean TRE of [Formula: see text] for the rigid registration and [Formula: see text] for the nonrigid registration, which is favorably comparable to a clinical requirement for an error of less than 2.5 mm. A landmark-based nonrigid 3-D MR-TRUS registration approach is proposed, which takes into account the correspondences on the prostate surface, inside the prostate, as well as the centroid of the prostate. Experimental results indicate that the proposed method yields clinically sufficient accuracy. PMID- 26158112 TI - Content-based image retrieval in radiology: analysis of variability in human perception of similarity. AB - We aim to develop a better understanding of perception of similarity in focal computed tomography (CT) liver images to determine the feasibility of techniques for developing reference sets for training and validating content-based image retrieval systems. In an observer study, four radiologists and six nonradiologists assessed overall similarity and similarity in 5 image features in 136 pairs of focal CT liver lesions. We computed intra- and inter-reader agreements in these similarity ratings and viewed the distributions of the ratings. The readers' ratings of overall similarity and similarity in each feature primarily appeared to be bimodally distributed. Median Kappa scores for intra-reader agreement ranged from 0.57 to 0.86 in the five features and from 0.72 to 0.82 for overall similarity. Median Kappa scores for inter-reader agreement ranged from 0.24 to 0.58 in the five features and were 0.39 for overall similarity. There was no significant difference in agreement for radiologists and nonradiologists. Our results show that developing perceptual similarity reference standards is a complex task. Moderate to high inter-reader variability precludes ease of dividing up the workload of rating perceptual similarity among many readers, while low intra-reader variability may make it possible to acquire large volumes of data by asking readers to view image pairs over many sessions. PMID- 26158113 TI - Comparison of retinal image evaluation techniques in novice clinicians. AB - Retinal fundus evaluation is learned through experience and training. This study aimed to determine the image presentation characteristics and the accompanying evaluation techniques, which led to the most accurate and efficient retinal pathology detection method. Phase I included 25 novice clinicians asked to evaluate 14 different pathologies using spatial versus temporal image presentations. Phase II included 25 different novice clinicians asked to evaluate five different simulated pathologies at three different pixel sizes presented in both spatial and temporal image presentations. Accuracy and speed of recognition were evaluated between the spatial and temporal presentations of the same simulated pathology. In phase l, subjects were significantly faster at simulated pathology detection using a temporal presentation with a 95% accuracy rate versus a spatial presentation with a 79% accuracy rate. In phase II, subjects demonstrated significant differences in speed of detection using the temporal technique at all 3 pixel number sizes with the greatest difference in detection times shown at the smallest retinal defects. Accuracy and speed of recognition in simulated pathology assessment were improved in a temporal presentation and the greatest improvements were demonstrated at the smallest pixel numbers. PMID- 26158114 TI - Variability and accuracy of different software packages for dynamic susceptibility contrast magnetic resonance imaging for distinguishing glioblastoma progression from pseudoprogression. AB - Determining whether glioblastoma multiforme (GBM) is progressing despite treatment is challenging due to the pseudoprogression phenomenon seen on conventional MRIs, but relative cerebral blood volume (CBV) has been shown to be helpful. As CBV's calculation from perfusion-weighted images is not standardized, we investigated whether there were differences between three FDA-cleared software packages in their CBV output values and subsequent performance regarding predicting survival/progression. Forty-five postradiation therapy GBM cases were retrospectively identified as having indeterminate MRI findings of progression versus pseudoprogression. The dynamic susceptibility contrast MR images were processed with different software and three different relative CBV metrics based on the abnormally enhancing regions were computed. The intersoftware intraclass correlation coefficients were 0.8 and below, depending on the metric used. No statistically significant difference in progression determination performance was found between the software packages, but performance was better for the cohort imaged at 3.0 T versus those imaged at 1.5 T for many relative CBV metric and classification criteria combinations. The results revealed clinically significant variation in relative CBV measures based on the software used, but minimal interoperator variation. We recommend against using specific relative CBV measurement thresholds for GBM progression determination unless the same software or processing algorithm is used. PMID- 26158115 TI - Fiber orientation measurements by diffusion tensor imaging improve hydrogen-1 magnetic resonance spectroscopy of intramyocellular lipids in human leg muscles. AB - Twelve healthy subjects underwent hydrogen-1 magnetic resonance spectroscopy ([Formula: see text]) acquisition ([Formula: see text]), diffusion tensor imaging (DTI) with a [Formula: see text]-value of [Formula: see text], and fat-water magnetic resonance imaging (MRI) using the Dixon method. Subject-specific muscle fiber orientation, derived from DTI, was used to estimate the lipid proton spectral chemical shift. Pennation angles were measured as 23.78 deg in vastus lateralis (VL), 17.06 deg in soleus (SO), and 8.49 deg in tibialis anterior (TA) resulting in a chemical shift between extramyocellular lipids (EMCL) and intramyocellular lipids (IMCL) of 0.15, 0.17, and 0.19 ppm, respectively. IMCL concentrations were [Formula: see text], [Formula: see text], and [Formula: see text] in SO, VL, and TA, respectively. Significant differences were observed in IMCL and EMCL pairwise comparisons in SO, VL, and TA ([Formula: see text]). Strong correlations were observed between total fat fractions from [Formula: see text] and Dixon MRI for VL ([Formula: see text]), SO ([Formula: see text]), and TA ([Formula: see text]). Bland-Altman analysis between fat fractions (FFMRS and FFMRI) showed good agreement with small limits of agreement (LoA): [Formula: see text] (LoA: [Formula: see text] to 0.69%) in VL, [Formula: see text] (LoA: [Formula: see text] to 1.33%) in SO, and [Formula: see text] (LoA: [Formula: see text] to 0.47%) in TA. The results of this study demonstrate the variation in muscle fiber orientation and lipid concentrations in these three skeletal muscle types. PMID- 26158116 TI - Automated working distance adjustment enables optical coherence tomography of the human larynx in awake patients. AB - Optical coherence tomography (OCT) provides structural information of laryngeal tissue which is comparable to histopathological analysis of biopsies taken under general anesthesia. In awake patients, movements impede clinically useful OCT acquisition. Therefore, an automatic compensation of movements was implemented into a swept source OCT-laryngoscope. Video and OCT beam path were combined in one tube of 10-mm diameter. Segmented OCT images served as distance sensor and a feedback control adjusted the working distance between 33 and 70 mm by synchronously translating the reference mirror and focusing lens. With this motion compensation, the tissue was properly visible in up to 88% of the acquisition time. During quiet respiration, OCT contrasted epithelium and lamina propria. Mean epithelial thickness was measured to be 109 and [Formula: see text] in female and male, respectively. Furthermore, OCT of mucosal wave movements during phonation enabled estimation of the oscillation frequency and amplitude. Regarding clinical issues, the OCT-laryngoscope with automated working distance adjustment may support the estimation of the depth extent of epithelial lesions and contribute to establish an indication for a biopsy. Moreover, OCT of the vibrating vocal folds provides functional information, possibly giving further insight into mucosal behavior during the vibratory cycle. PMID- 26158117 TI - Fast processing of digital imaging and communications in medicine (DICOM) metadata using multiseries DICOM format. AB - The digital imaging and communications in medicine (DICOM) information model combines pixel data and its metadata in a single object. There are user scenarios that only need metadata manipulation, such as deidentification and study migration. Most picture archiving and communication system use a database to store and update the metadata rather than updating the raw DICOM files themselves. The multiseries DICOM (MSD) format separates metadata from pixel data and eliminates duplicate attributes. This work promotes storing DICOM studies in MSD format to reduce the metadata processing time. A set of experiments are performed that update the metadata of a set of DICOM studies for deidentification and migration. The studies are stored in both the traditional single frame DICOM (SFD) format and the MSD format. The results show that it is faster to update studies' metadata in MSD format than in SFD format because the bulk data is separated in MSD and is not retrieved from the storage system. In addition, it is space efficient to store the deidentified studies in MSD format as it shares the same bulk data object with the original study. In summary, separation of metadata from pixel data using the MSD format provides fast metadata access and speeds up applications that process only the metadata. PMID- 26158118 TI - Dual-element needle transducer for intravascular ultrasound imaging. AB - A dual-element needle transducer for intravascular ultrasound imaging has been developed. A low-frequency element and a high-frequency element were integrated into one device to obtain images which conveyed both low- and high-frequency information from a single scan. The low-frequency element with a center frequency of 48 MHz was fabricated from the single crystal form of lead magnesium niobate lead titanate solid solution with two matching layers (MLs) and the high frequency element with a center frequency of 152 MHz was fabricated from lithium niobate with one ML. The measured axial and lateral resolutions were 27 and [Formula: see text], respectively, for the low-frequency element, and 14 and [Formula: see text], respectively, for the high-frequency element. The performance of the dual-element needle transducer was validated by imaging a tissue-mimicking phantom with lesion-mimicking area, and ex vivo rabbit aortas in water and rabbit whole blood. The results suggest that a low-frequency element effectively provides depth resolved images of the whole vessel and its adjacent tissue, and a high-frequency element visualizes detailed structure near the surface of the lumen wall in the presence of blood within the lumen. The advantages of a dual-element approach for intravascular imaging are also discussed. PMID- 26158119 TI - Diagnostic index of three-dimensional osteoarthritic changes in temporomandibular joint condylar morphology. AB - This study aimed to investigate imaging statistical approaches for classifying three-dimensional (3-D) osteoarthritic morphological variations among 169 temporomandibular joint (TMJ) condyles. Cone-beam computed tomography scans were acquired from 69 subjects with long-term TMJ osteoarthritis (OA), 15 subjects at initial diagnosis of OA, and 7 healthy controls. Three-dimensional surface models of the condyles were constructed and SPHARM-PDM established correspondent points on each model. Multivariate analysis of covariance and direction-projection permutation (DiProPerm) were used for testing statistical significance of the differences between the groups determined by clinical and radiographic diagnoses. Unsupervised classification using hierarchical agglomerative clustering was then conducted. Compared with healthy controls, OA average condyle was significantly smaller in all dimensions except its anterior surface. Significant flattening of the lateral pole was noticed at initial diagnosis. We observed areas of 3.88-mm bone resorption at the superior surface and 3.10-mm bone apposition at the anterior aspect of the long-term OA average model. DiProPerm supported a significant difference between the healthy control and OA group ([Formula: see text]). Clinically meaningful unsupervised classification of TMJ condylar morphology determined a preliminary diagnostic index of 3-D osteoarthritic changes, which may be the first step towards a more targeted diagnosis of this condition. PMID- 26158121 TI - Non-reducible palmar dislocation of the distal radioulnar joint. AB - A rare case of an isolated traumatic palmar dislocation of the distal radioulnar joint is presented. Clinically, there is a loss of pronation and supination. The dislocation was treated using an open reduction, reinsertion of the capsule ligamentous complex and temporary stabilization using K-wires. PMID- 26158120 TI - Assessing the accuracy and reproducibility of modality independent elastography in a murine model of breast cancer. AB - Cancer progression has been linked to mechanics. Therefore, there has been recent interest in developing noninvasive imaging tools for cancer assessment that are sensitive to changes in tissue mechanical properties. We have developed one such method, modality independent elastography (MIE), that estimates the relative elastic properties of tissue by fitting anatomical image volumes acquired before and after the application of compression to biomechanical models. The aim of this study was to assess the accuracy and reproducibility of the method using phantoms and a murine breast cancer model. Magnetic resonance imaging data were acquired, and the MIE method was used to estimate relative volumetric stiffness. Accuracy was assessed using phantom data by comparing to gold-standard mechanical testing of elasticity ratios. Validation error was [Formula: see text]. Reproducibility analysis was performed on animal data, and within-subject coefficients of variation ranged from 2 to 13% at the bulk level and 32% at the voxel level. To our knowledge, this is the first study to assess the reproducibility of an elasticity imaging metric in a preclinical cancer model. Our results suggest that the MIE method can reproducibly generate accurate estimates of the relative mechanical stiffness and provide guidance on the degree of change needed in order to declare biological changes rather than experimental error in future therapeutic studies. PMID- 26158122 TI - Score As You Lift (SAYL): A Statistical Relational Learning Approach to Uplift Modeling. AB - We introduce Score As You Lift (SAYL), a novel Statistical Relational Learning (SRL) algorithm, and apply it to an important task in the diagnosis of breast cancer. SAYL combines SRL with the marketing concept of uplift modeling, uses the area under the uplift curve to direct clause construction and final theory evaluation, integrates rule learning and probability assignment, and conditions the addition of each new theory rule to existing ones. Breast cancer, the most common type of cancer among women, is categorized into two subtypes: an earlier in situ stage where cancer cells are still confined, and a subsequent invasive stage. Currently older women with in situ cancer are treated to prevent cancer progression, regardless of the fact that treatment may generate undesirable side effects, and the woman may die of other causes. Younger women tend to have more aggressive cancers, while older women tend to have more indolent tumors. Therefore older women whose in situ tumors show significant dissimilarity with in situ cancer in younger women are less likely to progress, and can thus be considered for watchful waiting. Motivated by this important problem, this work makes two main contributions. First, we present the first multi-relational uplift modeling system, and introduce, implement and evaluate a novel method to guide search in an SRL framework. Second, we compare our algorithm to previous approaches, and demonstrate that the system can indeed obtain differential rules of interest to an expert on real data, while significantly improving the data uplift. PMID- 26158123 TI - Support Vector Machines for Differential Prediction. AB - Machine learning is continually being applied to a growing set of fields, including the social sciences, business, and medicine. Some fields present problems that are not easily addressed using standard machine learning approaches and, in particular, there is growing interest in differential prediction. In this type of task we are interested in producing a classifier that specifically characterizes a subgroup of interest by maximizing the difference in predictive performance for some outcome between subgroups in a population. We discuss adapting maximum margin classifiers for differential prediction. We first introduce multiple approaches that do not affect the key properties of maximum margin classifiers, but which also do not directly attempt to optimize a standard measure of differential prediction. We next propose a model that directly optimizes a standard measure in this field, the uplift measure. We evaluate our models on real data from two medical applications and show excellent results. PMID- 26158124 TI - Retraction Notice to: Ossifying Fibroma Tumor Stem Cells Are Maintained by Epigenetic Regulation of a TSP1/TGF-b/SMAD3 Autocrine Loop. PMID- 26158125 TI - Reply: To PMID 23588609. PMID- 26158126 TI - Reflections: Neurology And The Humanities. Wastebasket patient. PMID- 26158127 TI - Vocal Repertoire of Wild Blonde Capuchins (Sapajus flavius) and Contextual Use of Calls. AB - Despite advances in the study of capuchin monkeys (Cebus and Sapajus), there is fairly limited information on their vocal communication systems. The present study focused on investigating the structure and use of vocalizations by wild blonde capuchin monkeys, Sapajus flavius. The study subjects produced 29 different call types, which we grouped into 10 categories according to their behavioral context. The number of call types per context varied from one to six. Some of the call types in the vocal repertoire were only produced by individuals of specific age classes. The "nhan" call, for instance, was only emitted by infants, whereas the "ghrr" call was specific to adults. Other call types had no age-specificity and were produced by animals of two or more age categories. Discriminant Function Analysis correctly classified 77.4% of calls to type (n = 14 types). The "huh" and "huh-1var" calls, which are food-associated calls, were most commonly used, together representing approximately 52% of recorded vocalizations. Information on the vocal repertoire of blonde capuchins increases our knowledge of this very little known and Critically Endangered species. Ultimately, it may be used as a tool to help survey these animals in the wild and to assess welfare in captivity. PMID- 26158128 TI - [99mTc Tilmanocept and SPECT / CT to search after regional lymph node metastasis]. PMID- 26158129 TI - [Transoral video laryngoscopic surgery with good results]. PMID- 26158130 TI - [Risk of infection among biologics]. PMID- 26158132 TI - [How does periodontitis have an impact on RA]. PMID- 26158131 TI - [TNF-blocker therapy for Legionella]. PMID- 26158133 TI - Management of the Primary Tumor and Limited Metastases in Patients With Metastatic Pancreatic Cancer. AB - New combinations of cytotoxic chemotherapy have been proven to increase response rates and survival times compared with single-agent gemcitabine for patients with metastatic pancreatic cancer. These responses have been dramatic for a subset of patients, therefore raising questions about the management of limited metastatic disease with surgery or other ablative methods. Similarly, for patients having a complete radiographic response to chemotherapy in the metastatic compartment, whether to consider local therapy in the form of radiation or surgery for the primary tumor is now an appropriate question. Therefore, collaboration among experts in surgery, medical oncology, and radiation oncology has led to the development of guiding principles for local therapies to the primary intact pancreatic tumor for patients with limited metastatic disease and those who have had a significant response after systemic therapy. PMID- 26158134 TI - Systemic Therapy for Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck. AB - This article summarizes the systemic treatment options for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, with an emphasis on recommendations based on phase II and III comparison trials of commercially available agents. Many single-agent and combination regimens have activity against these cancers, but improvement in overall survival remains a challenge, and median survivals in this population with best available therapy remain less than 1 year. The major recent advancement has been the introduction of epidermal growth factor receptor inhibitors, with mixed success. Although single-agent treatment with methotrexate, paclitaxel, docetaxel, or 5 fluorouracil remains one standard for many patients, the use of cisplatin- or carboplatin-based multidrug regimens that include cetuximab has become more popular, primarily based on one randomized study demonstrating a modest survival improvement of approximately 3 months associated with the addition of cetuximab. The burdensome adverse event profile of multidrug regimens makes appropriate patient selection for such aggressive treatment challenging, and consideration should include factors such as need for palliation, performance status of the patients, history of prior treatment, convenience, and cost. Genetically targeted and immunologically mediated treatments are promising but remain experimental. Given the worrisome prognosis for these patients, innovative clinical trials are a good option for many patients and deserve support. PMID- 26158135 TI - In Memoriam: Carlos E. Baena-Cagnani. PMID- 26158136 TI - Comparison of Sorafenib and Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Study. AB - BACKGROUND/AIMS: This prospective non-randomized controlled trial aimed to compare the efficacy of sorafenib vs hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma. METHODOLOGY: Forty-seven patients treated with sorafenib (sorafenib group) and 77 patients treated with HAIC (HAIC group) were investigated retrospectively using propensity score matching (PSM) to minimize selection bias. The cumulative survival rate was investigated before and after PSM in each of the sorafenib and HAIC groups. The cumulative survival rate was compared between the sorafenib and HAIC groups, and among the TNM stage by the Liver Cancer Study Group of Japan (LCSGJ TNM stage). RESULTS: No significant difference was noted in overall survival (OS) between the sorafenib and HAIC groups regardless of before or after PSM. On comparison of the cumulative survival rate between the groups by the same LCSGJ TNM stage, significant prolongation of OS was noted in stage IVB only in the sorafenib group (p = 0.032) after PSM. CONCLUSIONS: It may be better to actively introduce sorafenib for stage IVB, i.e., patients with extrahepatic metastasis. PMID- 26158137 TI - The Clinical Evaluation of Laparoscopic Transcystic Duct Common Bile Duct Exploration in Elderly Choledocholithiasis. AB - Aims: To evaluate the feasibility and safety of Laparoscopic transcystic duct common bile duct exploration(LTCBDE) in elderly patients. METHODOLOGY: Between Jan 2010 and Dec 2011, 308 elderly patients (age 65 years) with CBD stones underwent surgery. 165 were initially treated with LTCBDE, 143 patients underwent open choledocholithotomy surgery. Two groups were compared with operative duration, incidence of postoperative complication, and the average days of in hospital. RESULTS: The LTCBDE was performed successfully in 157 of 165 patients 95.15%. 3 cases were converted to laparotomy and the other 5 were changed to laparoscopic choledocholithotomy and T-tube drainage. All he elderly patients receiving LTCBDE were dealt with primary closure of cystic duct. There were no severe complications such as bleeding and residual stones.The average duration of surgery was 102 +/- 35 min and the mean blood loss 43 +/- 20 ml. The postoperative hospital day was 3 +/- 0.5 days. 143 patients underwent open choledocholithotomy surgery. There were 2 (1.4%) cases abdominal wall incision infection, 5 (3.5%) cases pulmonary infection, 2 (1.4%) bile leakage, and 1 (0.7%) local bile leakage for part T-tube pulled out postoperation. The operation duration was about 120 +/- 30 minutes, and postoperative hospital day 7 +/- 1.5 days CONCLUSIONS: Elective LTCBDE to treat CBD stones in elderly patients is safe and effective. PMID- 26158138 TI - The Loop-Tip Wire for Selective Cannulation during ERCP in Patients with Billroth II Anastomosis: A Preliminary Feasibility Study. AB - BACKGROUND/AIMS: Selective cannulation of common bile duct remains technically challenging in patients with Billroth II anastomosis due to an altered anatomy. We aimed to determine the feasibility of performing wire-assisted cannulation using a loop-tip wire during ERCP in patients with Billroth II anastomosis. METHODOLOGY: We retrospectively analyzed a database of nine patients with Billroth II anastomosis who underwent ERCP using a loop-tip wire from January 2009 to July 2013 in the Hallym University Sacred Heart Hospital. Clinical characteristics and procedure-associated clinical outcomes were analyzed. RESULTS: The mean age of the patients was 73.7 years, and the male/female ratio was 2:1. The success rate of selective biliary cannulation was 77.8%. The mean cannulation time was 3.6 minutes (range, 1-9 minutes). Two patients who had failed in selective cannulation underwent infundibulotomy using a needle-knife papillotome, but one of the two patients had failed in biliary stone removal and finally underwent surgery. Six patients underwent endoscopic sphincterotomy. Complete clearance of bile duct stones was achieved in seven patients in one session. There was one case of mild post-ERCP pancreatitis (11.1%). CONCLUSIONS: The loop-tip wire can be an alternative instrument for wire-assisted selective cannulation in patients with Billroth II anastomosis. PMID- 26158139 TI - The Impact of Body Mass Index as a Predictive Factor of Steatocholecystitis. AB - BACKGROUND/AIMS: Obesity is a chronic inflammatory condition and is strongly linked to raised levels of pro-inflammatory factors and may lead to fatty infiltration of multiple internal organs including the gallbladder and liver, causing organ dysfunction. This study was performed to evaluate the relationship between body mass index (BMI) and acute and chronic cholecystitis, and cholecystitis and cholesterolosis. We investigated the clinical implications of BMI as a predictive factor of cholesterol associated cholecystitis. METHODS: This retrospective study covered the period from January 2007 to December 2011, we included 1,158 patients who had cholecystectomy. We excluded patients with gallbladder cancer, adenomyomatosis, and cholesterolosis without cholecystitis. Finally, we investigated the data of a total of 1,109 patients with cholecystitis. Laboratory test results and clinical data such as age, sex, BMI, height, weight and underlying diseases were examined. We retrospectively investigated acute and chronic cholecysti tis, cholesterol polyps, and other gallbladder diseases such as gallbladder cancer and adenomyomatosis according to the histopathologic findings. RESULTS: There was a significant difference of BMI between patients with cholecystitis with cholesterolosis and without cholesterolosis (P = 0.001). Among patients who had cholecystitis with cholesterolosis, the BMI was 25.2 kg/m2. Among patients with cholecystitis without cholesterolosis, the average BMI was 24.3 kg/m2. Weight, systolic blood pressure, platelet count, glucose, triglyceride, and LDL-cholesterol were different between the groups above (P < 0.05). However, there was no significant difference in BMI between acute and chronic cholecystitis (P = 0.05). CONCLUSIONS: BMI was associated with steatocholecystitis. However, we cannot predict whether cholecystitis is acute or chronic according to the BMI. We suggest that BMI can be used as one of the predictive factors of steatocholecystitis for obese patients. PMID- 26158140 TI - Preoperative Portal Vein Embolization before Major Hepatectomy in Patients with Excess Bilirubin does not Affect Hypertrophy of Remnant Liver and Postoperative Outcomes. AB - BACKGROUND/AIMS: Preoperative portal vein embolization (PVE) has commonly used in patients who were planned major hepatectomy for avoiding the postoperative liver failure. However, the influence of serum bilirubin concentration at the time of PVE on liver regeneration and subsequent surgical outcomes have not been clarified. METHODOLOGY: We retrospectively analyzed 36 patients who scheduled major hepatectomy for hepatobiliary malignancies after PVE. All patients had obstructive jaundice and underwent biliary drainage before PVE. Factors related to hypertrophy ratio of remnant liver volume (RLV) following PVE and postoperative morbidity and mortality were analysed. RESULTS: Hypertrophy ratio of RLV at 2 weeks after PVE correlated positively with emboli zed liver volume/entire liver volume (ELV) ratio and mean computed tomography attenuation of the liver. RLV/ELV ratio <40% represented the only significant risk factor for postoperative hyperbilirubinemia and mortality after major hepatectomy. Serum bilirubin concentration at the time of PVE did not affect hypertrophy ratio of RLV and postoperative outcomes after major hepatectomy. CONCLUSIONS: PVE in patients with elevated bilirubin levels dose not affect in hypertrophy of remnant liver and postoperative outcomes of subsequent major hepatectomy. Therefore, PVE can perform safely and effectively in patients with obstructive jaundice regardless of serum bilirubin concentration. PMID- 26158141 TI - Value of CT for ERCP Endoscopists to Identify the Type of Gastroenteric Anastomosis in Patients with Previous Subtotal Gastrectomy. AB - Background/Aims: The aim of this study was to evaluate whether endoscopic retrograde cholangiopancreatography (ERCP) endoscopists can distinguish the type of gastroenteric anastomosis in patients with previous subtotal gastrectomy based on CT findings, particularly in biliary emergencies. METHODOLOGY: A total of 70 abdominal CT scans from patients who had undergone gastrectomy (n = 36, Billroth I; n = 34, Billroth II) were enrolled. The shuffled images were reviewed by 3 ERCP endoscopists blinded to clinical data. The endoscopists were asked to provide the most probable type of anastomosis. The sensitivity, specificity and interobserver agreement were analyzed for identifying Billroth II gastrectomy. RESULTS: The ERCP endoscopists were able to identify the type of anastomosis based on CT findings with a sensitivity, specificity and interobserver agreement of 100%, 97.2%, and 0.98, respectively. The key CT features for distinguishing Billroth II gastrectomy from Billroth I gastrectomy were: i) loss of continuity between the remnant stomach and duodenum; ii) less distended duodenal bulb; iii) the presence of a closed duodenal stump with surgical staples and iv) the presence of continuity between the remnant stomach and the jejunum. CONCLUSIONS: ERCP endoscopists were able to use CT findings to distinguish the type of gastroenteric anastomosis in patients with previous gastrectomy. PMID- 26158142 TI - To Stent or Not To Stent Hepaticojejunostomy--Analysis of Risk Factors for Postoperative Bile Leaks and Surgical Complication. AB - BACKGROUND/AIMS: Hepaticojejunostomy (HJ) has remained an important component of many surgical procedures. Biliary leaks after HJ represent a major complication carrying a high risk for prolonged hospital stay, biliary peritonitis, and the need for placing interventional drains or even conducting a re-laparotomy. The aims of this study were to define predictive factors associated with the incidence of bile leaks and to compare the results of anastomotic stenting of HJ with those obtained without stenting. METHODOLOGY: A retrospective study was performed on patients who underwent HJ between January 2000 and December 2010 at Gunma University Hospital, Department of Surgery I. A bile leak was defined as a bilirubin concentration in the drains exceeding serum bilirubin or occurrence of a biloma requiring drainage. Transanastomotic techniques for HJ were compared between the stented (external diverting stent, internal stent) and non-stented groups with respect to bile leaks. RESULTS: An HJ leak was demonstrated in 15 patients (12.4%); the overall surgical morbidity was 29.2%. The incidence of clinically relevant bile leaks after HJ was significantly associated with simultaneous liver resection, preoperative biliary drainage (PBD) and the placement of stents through the anastomosis. CONCLUSIONS: We conclude that the routine use of a biliary stent is not justified before and after surgery. We consider that stenting is unnecessary when a full anastomosis of the bile duct to the jejuna mucosa is performed. However, when an anastomosis of the intrahepatic bile duct to the jejuna mucosa is performed, more careful method must be exercised during an anastomotic procedure. PMID- 26158143 TI - Concomitant Precise Hemihepatectomy to Improve the Efficacy of Surgical Treatment for Hilar Cholangiocarcinoma: Analysis of 38 Cases. AB - Background/Aims: Hilar cholangiocarcinoma (HC) is associated with low rates of resectability and curability, high morbidity and mortality, and poor long-term survival. Radical tumor resection with negative surgical margins provides the only chance of cure and long-term survival. The present study was to investigate the efficacy of concomitant precise hemihepatectomy for HC. METHODOLOGY: The clinical data of 38 patients who underwent surgery for HC with concomitant precise hemihepatectomy at our center from January 2009 to October 2012 were analyzed retrospectively. Survival curves were generated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazards model. RESULTS: R0 resection was performed in 32 patients (84.2%), R1 resection in 4 (10.5%), and R2 resection in 2 (5.3%). Two patients died during the perioperative period (mortality rate 5.3%). The most common postoperative complications were bile leakage (28.9%, 11/38) and hepatic dysfunction (21.1%, 8/38). The overall 1-, 2-, and 3-year survival rates were 65.8%, 36.8%, and 21.1%, respectively. The median survival time was 22.0 months. There were significant differences in survival between R0 and R1/R2 resection (chi2 = 4.516, P < 0.05) and between N0 and N1/N2 disease (chi2 = 10.397, P < 0.05). Univariate and multivariate analysis identified a positive surgical margin, lymph node metastasis and hepatic artery resection as prognostic indicators. CONCLUSIONS: Concomitant precise hemihepatectomy significantly improves the efficacy of radical surgical resection for HC. Precise liver resection, preservation of the hepatic artery, and selective preoperative biliary drainage are important to minimize postoperative morbidity and mortality. PMID- 26158144 TI - Safety of Human Hepatoma Cell-Line Constructing Bioartificial Liver Supporting System Treating Patients with Liver Failure. AB - BACKGROUND/AIMS: To observe the clinical safety of bioartificial liver supporting system constructed by human hepatoma cell line. METHODOLOGY: Seventeen patients with liver failure were treated with C3A-cell-constructed bioartificial liver supporting system, contrasting the difference of biochemical results and imaging data with 9 patients treated with non-bioartificial liver during 5-year treatment. RESULTS: 11 cases of Treatment Group survived at 3 months' follow-up, among whom 2 cases underwent hepatic transplantation. 9 cases without hepatic transplantation survived in 5-year follow-up, and 1 of them was found to occur focal liver lesion at the 5th years, and had hepatic lobectomy. Pathological prompt: hepatocellular carcinoma with moderate differentiation. Totally 4 patients in Control Group survived after 3 months' follow-up, including 1 patient of hepatic transplantation. All the 3 patients without hepatic transplantation survived the last 5-year follow-up, with basically normal biochemical indicators and no focal liver lesion were found by imaging examination. CONCLUSIONS: It was safe to use bioartificial liver constructed by tumor cell line C3A to treat liver failure. PMID- 26158145 TI - Comparative Study of Intragastric Balloon and Cognitive-Behavioral Approach for Non-Morbid Obesity. AB - BACKGROUND/AIMS: Intragastric balloon (IGB) and cognitive-behavioral therapy (CBT) are possible options for weight reduction. The aim of our study was to compare their effectivness in inducing weight loss and metabolic changes accompanying weight loss in non-morbidly obese patients. METHODOLOGY: Subjects were required to be between 18 and 55 years old and to have a BMI between 30 and 45 to be eligible. Exclusion criteria, besides those for IGB placement, were the presence of diabetes, depression, binge-eating disorder and the use of medications that affect body weight. Anthropometric, biochemical and blood pressure measurements were performed at baseline and after 6 months. A total of 114 subjects were recruited to the study and assigned to IGB (n = 60) or CBT group (n = 54). All patients completed the study. RESULTS: After 6 months, patients treated with IGB lost significantly (P < 0.01) more weight (%EWL = 44.6 +/- 23.9) than patients who participated in CBT (%EWL = 24.3 +/- 16.0). In IGB group 75% of patients achieved >= 10% loss of initial weight, and 42.6% of patients in CBT group respectively. A significant improvement in all indices of metabolic syndrome except HDL cholesterol was seen in both treatment groups but much more in subjects treated with IGB. CONCLUSIONS: Our results confirmed that intragastric balloon is useful method for promoting weight loss. Due to improvement of metabolic parameters and substantial benefit on liver function, obese people with metabolic syndrome appear to be the best candidates for IGB placement. Combining intragastric balloon treatment with cognitive-behavioral approach might prove valuable for even greater weight loss. PMID- 26158146 TI - Feasibility of Chemotherapy in Patients with Inflammatory Bowel Disease-Related Gastrointestinal Cancer. AB - BACKGROUND/AIMS: Long-standing inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), is a known risk factor for gastrointestinal (GI) cancer, especially colorectal cancer (CRC). However, the feasibility of chemotherapy for IBD-related GI cancer is not well understood in terms of efficacy and adverse events, because there are fewer GI cancer patients with IBD than without IBD. METHODOLOGY: We retrospectively analyzed the medical records of eight IBD patients (CD = 5 and UC = 3) who received chemotherapy for IBD-related GI cancer between April 2003 and March 2013. RESULTS: The most common gastrointestinal adverse event was diarrhea (75%); 38% of patients experienced grade 3 diarrhea. Moreover, all grade 3 diarrhea occurred in patients with CD. The most common hematologic adverse events were anemia (75%), leukopenia (38%), and neutropenia (30%); 25% of patients experienced grade 3 neutropenia. The other severe adverse events were grade 3 AST and ALT elevation (13%). CONCLUSIONS: In this study, the incidence of grade 3 diarrhea was higher in patients with CD. The length and dysfunction of the small intestine is the most likely reason that diarrhea occurred more frequently in patients with CD. PMID- 26158147 TI - Bile Duct Injury after Transcatheter Arterial Chemoembolization: Risk Factors and Clinical Implications. AB - BACKGROUND/AIMS: The current study aims to investigate the risk factors and clinical implications of bile duct injury after performing transcatheter arterial chemoembolization (TACE) for the treatment of patients with hepatic malignancy. METHODOLOGY: A total of 2340 patients with hepatic malignancies underwent 5656 TACE procedures without any radiographic evidence of biliary abnormalities pre TACE. Of these, 40 patients developed bile duct injuries 3 weeks to 3 months after TACE. RESULTS: TACE-induced bile duct injuries occurred in 30 out of 348 patients with liver metastatic tumors (8.6%) and in 10 out of 1992 patients with hepatocellular carcinoma (HCC) (0.5%). Bile duct injuries, including focal (n = 12) and multiple intrahepatic bile duct dilatation (n = 16), along with cystic lesions or bilomas (n = 12), were identified during follow-up post-TACE imaging. In addition, 6 patients with multiple bile duct injuries presented mild jaundice, and 8 patients with large biloma showed associated serious bacterial infections. The remaining 26 patients were asymptomatic. Biliary injury-related mortality occurred in 4 patients (10%). CONCLUSIONS: Knowledge of TACE-induced bile duct injury imaging findings can help interventional radiologists in providing correct diagnosis and treatment. Awareness of patients with high-risk factors may also reduce post-TACE ischemic biliary injuries. PMID- 26158148 TI - Efficacy of Sorafenib for Advanced Hepatocellular Carcinoma and Prognostic Factors. AB - BACKGROUND/AIMS: Sorafenib, a drug that inhibits Raf serine/threonine kinases mediating cell proliferation and receptor tyrosine kinases involved in angiogenesis, is approved for treatment of advanced hepatocellular carcinoma. The study aims to evaluate the efficacy and analyze the prognostic factors of sorafenib treatment in patients with advanced hepatocellular carcinoma (HCC). METHODOLOGY: Consecutive cases of HCC were treated with sorafenib (400 mg, Bid). Baseline clinical parameters, adverse events and survival were collected. RESULTS: A total of 60 patients received sorafenib and transarterial therapy. There was no CR; 2 (3.3%) patients achieved partial response, but 30 patients (50.0%) achieved stable disease. The median follow-up time was 16 months. The median OS and median TTP were 13.6 months and 4.4 months respectively. The common adverse events were dermal reaction (60.0%, 36/60), diarrhea (46.7.0%, 28/60), hypertension (5.0%, 3/60), hair loss (16.7%, 10/60), myelosuppression (20.0%, 12/60), and liver dysfunction (25.0%, 15/60). In most patients, these side effects were mild-to-moderate, and alleviated remarkably after symptomatic treatment. The patients with lower tumor burden and without extrahepatic spread had better prognosis. CONCLUSIONS: Soafenib is effective for unresectable primary HCC with tolerable toxicity. Tumor stage is a predominant prognostic factor. PMID- 26158149 TI - Evaluation of Preoperative Risk Factor for Converting Laparoscopic to Open Cholecystectomy: A Meta-Analysis. AB - Background/Aims: Laparoscopic cholecystectomy (LC) has become the gold standard for treating sy!m!ptomatic cholelithiasis. However, there are still some risk factors will lead to conversion to o!p!en cholecystectomy. The main aim of this meta-analysis is to evaluate preoperative risk fact!o!rs for converting laparoscopic to open cholecystectomy (LOC). METHODOLOGY: Evaluated risk factors of all clinical studies published from 1990 to 2012. All kinds of converting laparoscopic to open cholecystectomies were searched in the the Med-line, Embase, Science Citation Index, and PubMed databases. Random and fixed-effect models were used to aggregate the study endpoints and assess heterogeneity. The RevMan 5.2 was used for pooled estimates. RESULTS: Eleven NRCTs containing 14645 patients (940 in the LOC group and 13705 in the LC group) were included in the present meta-analysis. From the pooled analyses, age > 65 years (OR = 1.83, 95% CI (1.31, 2.45), P < 0.0001), male gender (OR = 2.23, 95% CI (1.59, 3.12), P < 0.00001), Diabetes Mellitus (OR = 1.89, 95% CI (1.30, 2.75), P = 0.0009), acute cholecystitis (OR = 3.37, 95% CI (1.83, 6.20), P < 0.0001), thickened gallbladder wall (OR = 6.04, 95% CI (4.11, 8.88), P < 0.00001) and previous upper abdominal surgery (OR = 4.43, 95% CI (2.17, 9.04), P < 0.00001) were independent predictive risk factors for conversion. Previous lower abdominal surgery, preoperative endoscopic retrograde cholangiopancreatography (ERCP) and the gallstone pancreatitis were not significantly associated with conversion (all P > 0.05). CONCLUSION: Our meta-analysis indicates that age > 65 years, male gender, acute cholecystitis, t!hickened gallbladder wall, Diabetes Mellitus and previous upper abdominal surgery were sign!i!ficantly associated with increased risk of conversion. Evaluating these factors was useful for t!h!e doctors to make suitable operation scheme. PMID- 26158150 TI - Management of Traumatic Splenic Rupture in Adults: A Single Center's Experience in Mainland China. AB - BACKGROUND/AIMS: We evaluated the effectiveness of various therapies to treat the traumatic splenic rupture by using data from our single center. METHODOLOGY: From July 2008 to Jan 2014, 125 patients who were diagnosis spleen rupture without other organ injury were included into our present study. We divided these patients into two groups according to the managements of the splenic rupture: the operative management (OM) group (48 patients) and the non-operative management (NOM) group (77 patients). We compared the baseline characteristics and long-term outcomes of two groups. the OM group was divided into three sub-groups according to the different operative methods: the total splenectomy group, partial splenectomy group and radiofrequency ablation (RFA) group. RESULTS: Splenic injuries were most commonly observed in abdominal trauma: traffic accidents (49 cases), fall from height (36 cases), strike (22 cases), assaults (11 cases), and sports (7 cases). Of the patients included in our study, 48 patients accepted OM, and 77 patients accepted NOM. The baseline characteristics, including age, gender, BMI, and underlying diseases, were comparable between the two groups. However, the OM group patients exhibited more severe splenic rupture according to the AAST grade (P = 0.000). The three subgroups in the OM group (total splenectomies group (26 cases), partial splenectomy (12 patients), RFA-assisted spleen-preserving surgery (10 patients) exhibited no significant differences with respect to intraoperative data or postoperative recovery. The length of hospital stay in the NOM group was significantly longer than that in the OM group (6.8 +/- 1.4 VS 3.4 +/- 0.8, P = 0.000), but the OM and NOM patients reported comparable quality of life according to the SF-36 scale. CONCLUSION: In conclusion, the outcomes of operative management for splenic rupture were comparable, and the OM and the NOM patients exhibited a similar quality of life after splenic rupture, although longer hospital stays were observed in the NOM group. PMID- 26158151 TI - Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy in Combination with Intravenous Chemotherapy as Postoperative Adjuvant Therapy for Advanced Gastric Cancer. AB - BACKGROUND/AIMS: The aim is to evaluate the preliminary efficacy and side effects of paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy in combination with cisplatin hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) as postoperative adjuvant therapy for patients of locally advanced gastric cancer (GC) at high risk for recurrence after curative resection. METHODOLOGY: Four GC patients who underwent radical gastrectomy with D2 lymphadenectomy were enrolled. All patients received paclitaxel 135 mg/m2 on day 1, 5-FU 500 mg/m2 on days 1-5, LV 200 mg/m2 on days 1-5 intravenous chemotherapy, cisplatin 75 mg/m2 on day 5, and HIPEC one month after surgery. It was repeated at 3 weeks intervals and at least two cycles administered. RESULTS: A total of 181 cycles of chemotherapy were administered (median, 4 cycles). The median disease free survival time of patients was 40.8 months. The median overall survival time was 48.0 months. The one-, two-, and three-year recurrence rates were 14.6%, 26.8%, and 46.3%, respectively. The main relapse patterns were remnant GC and metastases of retroperitoneal lymph nodes. The morbidity of grade 3 and 4 toxicities of myelosuppression, nausea/ vomiting were less than 10%. The side effects of grade 1 and 2 of hematologic toxicity, nausea and vomiting, abnormal function of liver, kidney or cardiac, fatigue and neurotoxicity were well tolerated. CONCLUSIONS: Cisplatin HIPEC combined with paclitaxel, 5 fluorouracil, and leucovorin intravenous chemotherapy regimen could improve the survival rate and decrease the postoperative recurrence of locally advanced GC. PMID- 26158152 TI - Accuracy of Endorectal Endoscopic Ultrasound (EUS) for Locally Advanced Rectal Cancer (LARC) Restaging After Neoadjuvant Chemoradiotherapy (NAT): A Meta Analysis. AB - BACKGROUND/AIMS: Endorectal endoscopic ultrasound (EUS) can provide accurate and reliable information for initial staging of locally advanced rectal cancer (LARC) in both the depth of rectal cancer penetration (T-stage) and regional lymph node involvement (N-stage). However, there is still no consensus about its accuracy in retagging LARC after neoadjuvant chemoradiotherapy (NAT). METHODOLOGY: In this study, we retrieved previous studies and performed a meta-analysis for assessing the accuracy of EUS for retagging of LARC after NAT. RESULTS: It was found the accuracy of EUS for T restaging of LARC was relatively low and over-staging was common, although the accuracy for assessing T3/4 was significantly higher than T0 T2 stage. The specificity of EUS for assessing N stage was relatively high, but the sensitivity was relatively low. CONCLUSIONS: Data obtained in this study confirmed the overall accuracy of EUS is not sufficient to serve as a basis for decisions on restaging Exploring the possible application of new techniques is necessary for better restaging. PMID- 26158153 TI - Prospective Blinded Comparison of Computed Tomographic Enterography and Small Bowel Endoscopy in Obscure Gastrointestinal Bleeding. AB - BACKGROUND/AIMS: This study investigated the value of computed tomographic enterography with new techniques, such as multi-planar reformation, curved planar reformation, and blood vessel reformation technique, in evaluation of obscure gastrointestinal bleeding by comparing computed tomographic enterography and small bowel endoscopy. METHODOLOGY: We retrospectively evaluated 30 patients with pathologically proven obscure gastrointestinal bleeding. Patients with acute gastrointestinal bleeding were excluded. All patients successfully underwent computed tomographic enterography and small bowel endoscopy at Yantai Yuhuangding Hospital. Results of both methods in the same patient were compared with pathologic biopsy results from clinical operations or endoscopy. RESULTS: Among the 30 patients retrospectively examined by computed tomographic enterography and small bowel endoscopy, the clinical diagnostic accuracy of the two methods was 70% (21/30) and 80% (24/30), respectively. Computed tomographic enterography and small bowel endoscopy showed no statistical difference in the diagnosis of obscure gastrointestinal bleeding (P = 0.37). CONCLUSIONS: Computed tomographic enterography can supplement or partly replace small bowel endoscopy in the diagnosis of obscure gastrointestinal bleeding. Computed tomographic enterography not only costs patients less and causes them less suffering, but is also technically easy to perform. PMID- 26158154 TI - Importance of the Postoperative Carcinoembryonic Antigen Level during Follow-Up after Curative Resection in Patients with Liver Metastatic Colorectal Carcinoma. AB - BACKGROUND/AIMS: To validate the conventional Japanese grading of liver metastasis for no residual tumor resection in Stage IV colorectal cancer (CRC) with liver metastasis and to identify risk factors for postoperative recurrence. METHODOLOGY: The subjects of this study were 1792 Stage IV CRC patients with liver metastasis. RESULTS: In 1792 cases, including unresectable cases, there was a significantly different prognosis by grade (P < 0.0001). In 421 R0 cases, there was no significant difference between Grade A and Grade B (P = 0.8527). In 381 cases without extra-hepatic metastasis, the prognosis was not significantly different among three grades. On multivariate analysis, carcinoembryonic antigen within 3 months from R0 operation (3M-CEA) was an independent risk factor regardless of extrahepatic metastasis. There was a significantly different prognosis (P < 0.0001) among Grade A', defined as a normal 3M-CEA level, Grade B', defined as Grade A or B and an abnormal 3M-CEA level, and Grade C', defined as Grade C and an abnormal 3M-CEA level. CONCLUSIONS: The postoperative CEA level is an important risk factor during follow-up after curative resection in patients with liver metastatic colorectal carcinoma. The combination of the 3M-CEA level and conventional grading of liver metastasis is useful for follow-up of R0 resection cases. PMID- 26158155 TI - The Prognostic Value of Preoperative Serum CEA and CA19-9 Values in Stage I-III Colorectal Cancer. AB - BACKGROUND/AIMS: There is disagreement about the prognostic value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients who have stage I-III colorectal cancer. Therefore, we investigated the relationship between preoperative serum CEA and CA19-9 levels and clinical outcome in patients with this disease. METHODOLOGY: The study included 724 patients who had received radical resection for stage I-III colorectal cancer in Fudan University Shanghai Cancer Center. We retrospectively investigated the relationship between patients' characteristics and survival, using univariate and multivariate analyses. In multivariate analysis, factors found significant in the univariate analysis were compared with patients' outcomes. RESULTS: In univariate analysis, differentiation (P < 0.001), depth of invasion (P < 0.001), number of lymph node metastases (P < 0.001), and elevated levels of CEA (P < 0.001) and CA19-9 (P < 0.001) were closely correlated with patients' survival. In multivariate analysis, the number of lymph node metastases (P < 0.001), preoperative CA19-9 (P = 0.015) and CEA (P = 0.028) values, differentiation (p = 0.040) and depth of invasion (p = 0.039) were independent prognostic factors for survival. CONCLUSIONS: Preoperative CA19-9 and CEA have independent prognostic values in stage I-III colorectal cancer. Elevation of and both CEA and CA19-9 values predicted the worst outcome. PMID- 26158156 TI - Number of Lymph Nodes in Rectal Cancer is Correlated with Response to Preoperative Chemoradiotherapy but is not Associated with Patient Survival. AB - BACKGROUND/AIMS: We aimed to clarify the oncological significance of the number of lymph nodes in rectal cancers treated with preoperative chemoradiotherapy. METHODOLOGY: We studied 126 curatively operated patients with clinical T3-T4 and M0 rectal cancers. The number of lymph nodes and clinicopathological features were compared between the patients treated with surgery alone (OP group, n = 45) and those treated with preoperative chemoradiotherapy (50-50.4 Gy in 25-28 fractions with tegafur-uracil and leucovorin, CRT group, n = 81). Factors influencing lymph node count and its prognostic significance were analyzed. RESULTS: The CRT group had significantly fewer lymph nodes than the OP group (12.4 vs. 21.1, P < 0.0001). High histological regression of rectal lesions was significantly correlated with decreased lymph node count in the CRT group. In the OP group, the 5-year cancer-specific survival rate of the patients with 12 or more lymph nodes was significantly better than those with fewer than 12 lymph nodes (75.1% vs. 33.3%, P = 0.02); in the CRT group, on the other hand, these survival rates did not differ (84.5% vs. 77.5%, P = 0.6). CONCLUSIONS: The number of lymph nodes in rectal cancer was correlated with the response of primary rectal lesions to chemoradiotherapy, and was not associated with patient survival. PMID- 26158157 TI - The Effect of Pyridoxine for Prevention of Hand-Foot Syndrome in Colorectal Cancer Patients with Adjuvant Chemotherapy Using Capecitabine: A Randomized Study. AB - BACKGROUND/Aims: To determine the effect of the pyridoxine for prevention of hand foot syndrome in colorectal cancer patients with adjuvant chemotherapy using capecitabine. METHODOLOGY: Colorectal cancer patients scheduled for capecitabine chemotherapy as adjuvant setting were randomly assigned to with or without concurrent oral pyridoxine (60 mg/d) groups. Patients were monitored whether being a development of National Cancer Institute Common Toxicity Criteria grade 2 or worse HFS until chemotherapy ended. RESULTS: Sixty patients were enrolled in this study. Relative dose intensity was 89.5% in total. The median number of chemotherapy cycles to grade 2 or worse HFS was four in both groups. Grade 2 or worse HES developed in 18 (60.0%) of 30 control patients and in 18 (60.0%) of 30 pyridoxine patients. The cumulative dose of capecitabine to grade 2 or worse HFS was not different between the two groups. CONCLUSIONS: Pyridoxine is not effective in prevention of capecitabine-associated HFS. PMID- 26158158 TI - Simultaneous Resection of Colorectal Cancer and Liver Metastases through Hand assisted Laparoscopic Surgery: Preliminary Exploration. AB - BACKGROUND/AIMS: To describe the initial experience of simultaneous resection of colorectal cancer and liver metastases through hand-assisted laparoscopy (HALS). METHODOLOGY: After endotracheal general anesthesia, patients were placed in the Trendelenburg with lithotomy position. A 5-cm longitudinal subumbilical port was created, and the Lap Disc device was placed and pneumoperitoneum was established. A laparoscope was inserted to explore the liver and the whole pelvic cavity. The surgeon stood on the right side or between the patient's legs, and a 10-mm trocar was placed in the abdominal wall based upon the location of the tumor. The liver and the colorectal lesion were reselected with the assisted-hand through the Lap Disc to establish the possibility of resection, the tumor margin, and metastasis. RESULTS: Simultaneous resection of colorectal cancer and liver metastases through HALS were successful in all eight patients with operating time of 2-4 h. Average intraoperative blood loss was 100-300 ml, and no severe postoperative complications were observed. The average length of postoperative hospital stay was 7.5 days. CONCLUSIONS: HALS for simultaneous resection of colorectal and metastatic liver cancer has the advantages of safety, feasibility, minimal invasion, shorter operation time, reduced operative difficulty less pain and rapid recovery. PMID- 26158159 TI - A Multicenter Feasibility Study with S-1, Oxaliplatin and Oral Leucovorin (SOL) for the Patients with Untreated Metastatic Colorectal Cancer: The Result of Final Analysis. AB - BACKGROUND/AIMS: S-1 combination with oxaliplatin and oral leucovorin (SOL regimen) demonstrated well tolerability and efficacy in Japanese patients with metastatic colorectal cancer. The present study was conducted to confirm the safety and efficacy of SOL regimen in Chinese patients with untreated metastatic colorectal cancer. METHODOLOGY: We planned to enroll 20 untreated, unresectable or recurrent advanced colorectal adenocarcinoma patients. The treatment schedule comprised S-1 40-60 mg bid and leucovorin (LV) 25 mg bid for one week and 2 hour drip infusion of oxaliplatin (L-OHP) 85 mg/m2 on day 1, 1 week off, repeated every 2 weeks. The primary study endpoints were safety. Secondary endpoints were overall response rate (ORR), progression free survival (PFS) and time to treatment failure (TTF). RESULTS: A total of 21 patients (median age: 65; range: 30-79) were enrolled between August 2009 and December 2009. There were 15 patients with colon cancer and 6 with rectal cancer. Data cut-off date was April, 2011. In total, 168 cycles were administered (median 7 per patient; range 1-19). The common toxicities were neutropenia, thrombocytopenia, fatigue, diarrhea, nausea/vomiting, peripheral neurotoxicity and anemia. The common grade 3/4 adverse events were diarrhea (19.1%), thrombocytopenia (9.5%) and nausea/vomiting (9.5%). Dose-adjusted was executed in 11 patients owing to AEs, including S-1 in 9 cases and L-OHP in 9 cases. Death due to adverse event was not observed. Responses were evaluated in 20 patients with measurable disease, the overall response rate was 45% (1 CR and 8 PR: 95% CI, 23-68%) and the disease control rate was 70% (95% CI, 46%-88%). Pathologic complete response was observed in 1 patient after 5 cycles of treatment. Median PFS was 9.0 (95% CI, 3.7- 14.4) months. Median TTF was 4.2 (95% Cl, 3.5-5.6) months. CONCLUSIONS: This result indicates that the SOL regimen is well tolerated and effective in Chinese patients with metastatic colorectal cancer. PMID- 26158160 TI - The Number of Risk Factors Determines the Outcome Of Stage II Colorectal Cancer Patients. AB - BACKGROUND/AIMS: We evaluated the prognostic significance of clinicopathologic features recommended by the majority of guidelines for identifying high-risk stage it colon cancer patients. METHODOLOGY: We enrolled 665 stage II colorectal cancer patients at Taipei Veterans General Hospital in 2002-2006. Patients who received preoperative or postoperative chemotherapy were excluded (124). The measured endpoint was disease-free survival. RESULTS: Of 541 patients, 59 showed stage T4 tumors; 35, lymphovascular invasion; 19, poor differentiation, and 251, carcinoembryonic antigen levels of > 5 ng/mL; 53 underwent emergent operations. Colorectal cancer recurred in 84 patients. The 5-year disease-free survival rate was 84.5%. Univariate and multivariate analyses revealed 3 independent factors affecting the prognosis significantly tumor stage T4, high carcinoembryonic antigen level, and presence of lymphovascular invasion. Considering the cumulative effect of risk factors, the 5-year disease-free survival rate of patients with tumors without any risk factor was 90.2%, which was significantly better than that of patients with 1 or 2 risk factors (82.3%, 61.6%). CONCLUSIONS: Stage II colorectal cancer patients had excellent outcome. Ad juvant chemotherapy may be warranted for patients with multiple risk factors. PMID- 26158161 TI - Analysis of Recurrent Cases after Laparoscopic Surgery for Colorectal Cancer. AB - BACKGROUND/AIMS: Although previous reports have shown similar recurrence rates and patterns between laparoscopic and open surgery for colorectal cancer, precise data regarding recurrent cases are lacking. METHODOLOGY: From January 2007 to December 2011, 137 Patients with colorectal cancer underwent laparoscopic surgery at our hospital. Of the 137 patients, 7 patients with recurrence were analyzed for oncological factors. Their outcomes were compared with those of 13 patients with recurrence of 160 patients who underwent open surgery for colorectal cancer between January 2005 and December 2006. RESULTS: In the laparoscopic group, 1 of 37 patients (2.7%) with pathological Stage II (pStage) and 6 of 37 (16.2%) with pStage III experienced recurrence; in the open surgery group, 4 of 56 patients (7.1%) with pStage II and 9 of 63 patients (14.3%) with pStage III experienced recurrence. Although majority of recurrent patterns was distant metastasis, peritoneal metastasis was observed in 2 patients with pT3 tumors in the laparoscopic group. In contrast, all 3 patients with peritoneal recurrence in the open surgery group had pT4 tumors. In the laparoscopic group, 2 patients with peritoneal metastasis were pT3N1M0, and 1 of them revealed peritoneal carcinomatosis 6 months after surgery and developed chylous ascites as a postoperative complication. CONCLUSIONS: Although the recurrence rates and sites were similar between the laparoscopic and open surgery groups, peritoneal recurrence developed only in patients with pT3 tumors in the laparoscopic group. Exfoliation of tumor cells from divided lymphatic vessels might lead to development of peritoneal recurrence after laparoscopic surgery. PMID- 26158162 TI - Long Term Results of Esophageal Bypass for Corrosive Strictures without Esophageal Resection Using a Modified Left Colon Esophagocoloplasty--A Report of 105 Consecutive Patients from a Single Unit Over 30 Years. AB - BACKGROUND/AIMS: Esophageal stricture due to corrosive ingestion is a common cause of benign esophageal obstruction in developing countries. The immediate and long-term results of surgical bypass using a modification of the left colon conduit, will be reviewed. METHODOLOGY: From 1977 to 2008, 105 patients underwent esophageal bypass for corrosive esophageal strictures using this procedure which has several modifications, detailed in the text, from the conventional left colon conduit. RESULTS: Acids were the most common corrosive implicated (70.5%). Eighty nine patients underwent a bypass based on the left colic vessel through the substernal route. The subcutaneous route was used in the rest for varying reasons. Postoperatively three patients died. Conduit necrosis was seen in only one patient. Postoperative morbidity included pneumothorax in 15, cervical anastomotic stenosis in one, cervical anastomotic leak in 13 (less than 3% the last 75 cases) and recurrent laryngeal nerve palsy in 6 (5.7%). 72 patients had normal swallowing and 33 had only occasional minor difficulty with solid food on follow-up. CONCLUSIONS: Surgical bypass using a modification of the left colon esophagocoloplasty remains a reliable procedure with acceptable morbidity and good relief of dysphagia. PMID- 26158163 TI - Multimodality Treatment and Prognosis in Esophageal Squamous Cell Carcinoma Requiring Esophagectomy. AB - BACKGROUND/AIMS: MuItimodality treatment improves esophageal squamous cell carcinoma (ESCC) prognosis, however the most optimal treatment still remains controversial. METHODOLOGY: In 213 ESCC patients who had operation at Kitasato University Hospital between 1996 and 2007, prognosis was evaluated in terms of cStage and adjuvant therapy. RESULTS: Survival outcome of with the 62 cStage I ESCC were excellent (2 recurrences) with infrequent postoperative treatment (Adj). Of 129 ESCC patients with cStage II/III, 45 patients including suspicious cT4 (cT3.5) were given neoadjuvant therapy (Neo), and pStage 0/I patients showed excellent prognosis. Of 84 cStage II/III patients not given Neo, 67 (79.8%) underwent R0 esophagectomy, among whom 20 cases had pN0 (pStage II/IIa) with 3 recurrences (15%) despite infrequent Adj. On the other hand, among the 45 cStage II/III patients with Neo, 8 pStage IIa patients exhibited poor prognosis with 5 recurrences (62.5%) as well as pStage III/IV. In pStage IIb ESCC, cStage IIa showed poorer prognosis than cStage I/IIb (P = 0.0072). Among the 21 cStage IV ESCC patients, 5 long-term survivors were experienced by multimodality treatments. CONCLUSIONS: Both cStage and Neo greatly affect ESCC prognosis irrespective of identical pStage, which must be allowed for in order to determine therapeutic strategy against ESCC. PMID- 26158164 TI - Duodenal-Jejunal Bypass Improves Insulin Resistance by Enhanced Glucagon-Like Peptide-1 Secretion Through Increase of Bile Acids. AB - BACKGROUND/AIMS: The aim of this study is to investigate the mechanisms of improvement in insulin resistance after duodenal-jejunal bypass (DIB), especially regarding the correlation between bile acids and glucagon-like peptide-1 (GLP-1). METHODOLOGY: SD rats were divided into two groups: DIB or Sham group. Blood glucose, insulin, GLP-1, bile acids, and the number of L cells in the small intestine were investigated three weeks after the operations. Next, to assess the effect of the bile acids on GLP-1 secretion in ileum, bile diversion model (=inhibition of rapid bile exposure to the ileum; BD group) were performed and postoperative glycemic parameters were measured. RESULTS: DJB improved insulin resistance and increased GLP-1 compared with sham. Higher bile acids in DJB were found than that in sham. The number of L cells in the common limb of DJB was increased compared with that in the distal segment of sham. In BD group, insulin resistance had not improved. GLP-1, bile acids, and the number of L cells revealed no significant changes compared with sham. CONCLUSIONS: DJB has a potential to improve insulin resistance, which may be related to enhanced GLP-1 secretion through the increase of bile acids in the common limb of the small intestine. PMID- 26158166 TI - Detection of Portal Vein Stenosis by Technetium-99m-Diethylenetriaminepentaacetic Acid-Galactosyl Human Serum Albumin Liver Scintigraphy after Living-Donor Liver Transplantation. AB - BACKGROUND/AIM: To investigate portal vein stenosis after living-donor liver transplantation by liver scintigraphy. METHODOLOGY: A 63-year-old woman with hepatic cirrhosis due to autoimmune hepatitis underwent living-donor liver transplantation using a graft donated by her daughter. Technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (Tc-99m-GSA) scintigraphy was used to determine the maximum rate of Tc-99m-GSA removal (GSA Rmax) by hepatocytes, as a parameter of hepatic functional reserve. RESULTS: Conventional liver function parameters on laboratory tests and graft volume on computed tomography (CT) were almost unchanged at postoperative month (POM) 12. GSA-Rmax was 0.11 mg/min before surgery and increased 5-fold to approximately 0.5 mg/min at POM 1 and 3, followed by a decrease to 0.25 mg/min at POM 6 and 12. Enhanced CT did not detect blood flow in the intra- or extrahepatic portions of the portal vein at POM 12. The portal vein stenosis was dilated with a balloon catheter, followed by deployment of a self-expanding stent across the stenotic segment via the transileocolic vein. GSA-Rmax recovered to 0.5 mg/min at POM 15, and subsequently remained high. CONCLUSIONS: Decreased GSA-Rmax at POM 6 indicated that the portal vein stenosis was affecting graft function. Tc-99m-GSA liver scintigraphy may be a useful noninvasive method for evaluation of graft functional reserve. PMID- 26158165 TI - Upper Gastrointestinal Bleeding in Japanese Patients Prescribed Antithrombotic Drugs: Differences in Trends over Time. AB - BACKGROUND/AIMS: We studied the features of upper gastrointestinal bleeding (UGIB) in patients taking antithrombotic drugs. METHODOLOGY: The records of 430 patients taking antithrombotic drugs who underwent emergency endoscopy for UGIB in Saga Medical School Hospital between 2002 and 2011 were studied. We also compared the characteristics of our cohort of 11,919 patients prescribed antithrombotic drugs in our hospital between 2002 and 2011. UBGI patients of variceal bleeding were not included in this study. RESULTS: 186 patients presented with UGIB in the first period (2002-2006) and 244 in the second period (2007-2011). The proportion of patients infected with Helicobacter pylori was lower in the second period, while the proportion taking antithrombotic drugs rose significantly. Peptic ulcer disease was responsible for the majority of bleeding episodes; however, bleeding from other sources is increasing. In the whole cohort, the risk of UGIB was 1.08%; however, of the 31.8% who also took an acid secretion inhibitor only 18 (0.28%) developed bleeding. In contrast, 102 (1.87%) of those not taking an acid-secretion inhibitor developed UGIB, a statistically significant difference. CONCLUSION: Risk of UGIB in Japanese patients taking antithrombotics was 1.01% and the incidence is increasing. Acid-secretion inhibitors reduced the risk of antithrombotic drug-related UGIB. PMID- 26158167 TI - Feasibility and Advantages of Large Liver Hemangioma Treated with Laparoscopic Microwave Ablation. AB - BACKGROUND/AIMS: To evaluate feasibility and superiority of large liver hemangioma treated with laparoscopic microwave ablation. METHODOLOGY: Between March 2006 and May 2013, 47 patients with liver hemangioma (5-10 cm) were surgically treated in our department, and were randomly divided into three groups, laparoscopic microwave ablation group (treatment group), traditional opening group, and laparoscopic resection group. Three groups were compared in respect of postoperative ambulation time, gastrointestinal function recovery time, postoperative liver function recovery time, intraoperative blood loss, postoperative hospital stay, using SPSS13.0 software and analysis of variance, P < 0.05 indicates significant, then adopting Student-Newman-Keuls method to compare mean value of every two groups. And the treatment group of patients were tracked and reviewed. RESULTS: With regard to above aspects, treatment group and two control groups were compared, P < 0.05 was considered statistically significant, then the result of S-N-K method showed that the treatment group was far better than the control group in the above four areas, however compared with traditional opening group laparoscopic resection group did not demonstrate any superiority. Tracking the patients of treatment group proved no recurrence, and one case's CT films before and after surgery were compared, further confirming the feasibility of microwave ablation. CONCLUSIONS: To large hepatic hemangioma, laparoscopic microwave ablation in respect of intraoperative injury, postoperative recovery and costs is superior to other methods, and the treatment effect is certain, it's feasible and worthy of promotion. PMID- 26158168 TI - Disease-Free Survival after Simultaneous or Delayed Resection of Synchronous Colorectal Liver Metastasis and Primary Cancer. AB - BACKGROUND/AIMS: The purpose of our study was to compare disease-free survival in patients with synchronous colorectal liver metastasis who underwent delayed hepatic resection or simultaneous resection. METHODOLOGY: All patients who underwent a curative resection of synchronous colorectal liver metastasis between 2000 and 2006 in our tertiary care referral centre were retrospectively included in our study. Patients who underwent the first stage of a two-stage hepatectomy during the primary resection were included in the delayed resection group. Disease-free survival was studied using a Kaplan-Meier method. Prognostic factors for disease-free and overall survival were determined by multivariate analysis using Cox models. RESULTS: One hundred and five patients underwent 85 delayed resections and 20 simultaneous resections. Three and five-year disease-free survival did not differ significantly between simultaneous (50% and 40%) and delayed (65% and 34%) resection groups (P = 0.47). Preoperative carcinoembryonic antigen (HR = 2.05, 95% CI, 1.07-3.92) and presence of extra-hepatic metastasis (HR = 2.85, 95% CI, 1.08-7.54) were independent prognostic factors for disease free survival. Three and five-year overall survival did not differ either (23% and 23%; 24% and 20%, P = 0.13). CONCLUSIONS: Simultaneous resection of synchronous colorectal liver metastasis and primitive cancer does not appear to impair long-term disease-free survival. PMID- 26158169 TI - STAT3 activation mediates epithelial-to-mesenchymal transition in human hepatocellular carcinoma cells. AB - BACKGROUND/AIMS: Epithelial-to-mesenchymal transition (EMT) is critical for the development of the invasion and metastasis in human cancers. Recently, signal transducer and activator of transcription 3 (STAT3) activation has been linked to EMT program in breast cancer. However, the actual association of STAT3 activation with EMT, and its mediated tumor invasion and metastasis remains elusive in hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between STAT3 activation and EMT, as well as the underlying mechanism involved in HCC progression. METHODOLOGY: We treated SMMC-7721 cells with a known STAT3 activator, epithelial growth factor (EGF); in the absence or presence of JSI-124, a selective STAT3 inhibitor. The EMT-associated morphologic and molecular changes of cells were analyzed. The EMT-mediated HCC cell invasion, migration and adhesion were evaluated. RESULTS: In this study, we found that STAT3 activation induced by EGF was associated significantly with morphologic changes, cytoskeleton rearrangement and molecular changes consistent with EMT in SMMC-7721 cells; STAT3 activation-mediated EMT may be transcriptionally induced by Twist. STAT3 activation-mediated EMT also promoted HCC cell invasion, migration and adhesion significantly. CONCLUSIONS: In summary, our study show for the first time that STAT3 activation may induce invasion and metastasis through the mediation of EMT in HCC cells. Activated STAT3 and EMT markers can serve as molecular targets for HCC treatment. PMID- 26158170 TI - Limitations of Living Donor Liver Transplantation in Egyptian Children. AB - BACKGROUND/AIMS: In Egypt, the liver transplantation (LTx) program that became available since 2001 is a living donor program. We aimed to assess the obstacles to pediatric LTx. METHODS: Over a six-month-period, 41 pediatric patients were indicated for LTx; their ages ranged between 1.5 months to 17 years. Patients and potential donors were evaluated according to the program protocol. RESULTS: The obstacles for performing LTx were classified into recipient, donor and program obstacles or limitations. Each patient may have more than one limitation. Late presentation and co-morbid conditions were on the top of the recipient list of obstacles. Refusal of potential donors to donate was the commonest limitation on the donor side (33%). The commonest program limitations were young age and small size of the recipient. CONCLUSIONS: Limitations in recipient characteristics as well as donor shortage are still the main obstacles for living donor liver transplantation (LDLT) in our pediatric liver disease patients. Small weight and young age of potential LDLT candidates are the principle causes for delaying this life saving procedure. Increasing community awareness about living organ donation and nutritional support for end stage liver disease (ESLD) babies is pivotal, given our limitation to a living donor program. PMID- 26158171 TI - Treatment Outcomes and Predictors of Response in Treatment-Naive HCV Patients Treated with Peginterferon Alfa/Ribavirin in Real-World Italian Clinics: Sub Analysis from the PROPHESYS Cohort. AB - BACKGROUND/AIMS: Within Europe, Italy has the highest incidence of HCV. PROPHESYS was a large, non-interventional, multinational cohort study of patients treated with peginterferon alfa-2a or -2b/ribavirin for CHC; 22.4% of patients were from Italian centers. This sub-analysis evaluates real-life practice and treatment outcomes in Italy. METHODOLOGY: The PROPHESYS 2 cohort included 1604 HCV mono infected, treatment-naive patients. All patients were prescribed peginterferon alfa/ribavirin at the discretion of the treating physician according to country specific requirements. RESULTS: The majority of G1-3 patients were White/Caucasian and 48.4% had HCV G1 infection. Overall, SVR24 rates of 44.9%, 81.4% and 69.1% were achieved in G1-, 2- and 3-infected patients. In G1 patients, SVR24 rates declined with increasing FIB-4 score; this trend was not observed for G2/3-infected patients. Virologic response by Week 2 and 4 was highly predictive of SVR24 (G1: 91.7%, 84.8%; G2: 91.1%, 89.7%; G3: 92.9%, 86.7%, respectively). Absence of virologic response by Week 12 had the highest negative predictive value across genotypes. CONCLUSIONS: In Italian patients, a virologic response by Week 2 or 4 was highly predictive of SVR24 across genotypes. These data demonstrate the importance of monitoring on-treatment response to help guide treatment decisions. FIB-4 score correlated well with SVR24 in G1 patients. PMID- 26158172 TI - The Feasibility of Central Pancreatectomy for Blunt Pancreatic Trauma: A Comparative Study of Central and Distal Pancreatectomy. AB - BACKGROUND/AIMS: Central pancreatectomy (CP) is an alternative technique of distal pancreatectomy (DP) for focal pancreatic tumors; however, the feasibility of CP for pancreatic trauma has not been adequately assessed. METHODOLOGY: Patients who underwent CP (n = 8) or DP (n = 8) for pancreatic duct injuries following blunt trauma were reviewed. Patient demographics, status of pancreatic duct injuries, and perioperative outcomes were compared between procedures. RESULTS: Pancreatic duct injuries occurred at the neck of the pancreas in 63% patients (10/16). Patient demographics and perioperative outcomes were comparable between the CP and DP groups. Polytrauma was found in 38% patients in both groups. No differences were found between patients treated with CP and DP in overall blood loss (median: 1025 mL vs 1800 mL, P = 0.418) and surgical duration (median: 284 min vs 188 mm, P = 0.172). The incidence of pancreas-related complications was comparable between groups (CP: 50% vs. DP: 38%, P = 0.614. CONCLUSIONS: Blunt pancreatic duct injuries tend to occur at the pancreatic neck, leaving the body and tail of the pancreas intact. CP is feasible for blunt pancreatic trauma in hemodynamically stable patients. PMID- 26158173 TI - Parenchyma-Sparing Pancreatic Resections: With or Without a Pancreaticojejunostomy? AB - BACKGROUND/AIM: Parenchyma-sparing pancreatic resections are used in low-grade malignant tumors, but result in a high incidence of pancreatic fistula. Pancreaticojejunostomy to the site of resection might decrease the risk of pancreatic fistula. The purpose of this study was to evaluate the influence of pancreaticojejunostomy on the outcomes of parenchyma-sparing resections. METHODOLOGY: The study group consisted of 21 patients (M/F = 4:17, mean age = 47 years). Local tumor resection with a pancreaticojejunostomy was performed in 11 patients and enucleation in 10 patients. Both groups were compared retrospectively with regard to perioperative variables. RESULTS: The operative time was significantly shorter in the enucleation group (median 180 min vs. 222 min, P = 0.005). The overall surgical morbidity was similar in both groups (81% vs. 70%, P = 0.64). The rate of clinically significant pancreatic fistula (64% vs. 40%, P = 0.39), hemorrhagic complications (27% vs. 10%, P = 0.59) and wound infection (18% vs. 40%, P = 0.36) were comparable in both groups. One patient died after central pancreatectomy. There were no new-onset cases of diabetes mellitus postoperatively. CONCLUSIONS: Local resection combined with pancreaticojejunostomy is an option to avoid extensive resection of the pancreatic parenchyma, but is still associated with a high incidence of pancreatic fistula which is comparable to that after enucleation. PMID- 26158174 TI - Laparoscopic Supracolic Pancreaticoduodenectomy: A Novel Technique For Complete Uncinate Process Resection. AB - BACKGROUND: Laparoscopic pancreaticoduodenectomy represents one of the most advanced surgical approaches for periampullary and pancreatic head tumors. This article aims to describe the novel technique for complete resection of the uncinate process from supracolic compartment only and summarizes the results from our institute. METHODOLOGY: Retrospective review of prospectively maintained database was performed for patients who underwent laparoscopic pancreaticoduodenectomy from April 2008 to March 2012 at our institute. RESULTS: A total of 38 patients with a mean age of 56.5 years (range: 35-70) underwent laparoscopic pancreaticoduodenectomy with this novel approach. Complete resection of uncinate process was achieved in 33 (86.84%) patients. The mean total operative time and resection time was 231.70 mins (range: 210-450) and 116.50 mins (range: 80-250), respectively. The mean blood loss was 183 ml (range 60 340). Major perioperative morbidity included pancreatic anastomotic leak (n = 3), billiary leak (n = 1) and hemorrhage (n = 1). Mean hospital stay was 14 days (range: 12-25 days). CONCLUSION: This novel supracolic approach for laparoscopic pancreaticoduodenectomy is feasible, safe and less time consuming. This technique can help achieving oncological outcomes comparable to those of the other techniques; though with the minimum invasion. This procedure can be performed conveniently by surgeons with substantial knowledge, experience and skills. PMID- 26158175 TI - Pancreatoduodenectomy: Risk Factors of Postoperative Pancreatic Fistula. AB - BACKGROUND/AIMS: The aim of the present study is the analysis of risk factors of postoperative pancreatic fistula (POPF) and of clinical outcome after pancreatoduodenectomy (PD) in a retrospective multicentric review of the patient cohort. METHODOLOGY: From January 2003 to July 2013 143 patients underwent PD: 138 cases were included and 3 groups were identified according to the different types of anastomosis: Group 1 invaginating end-to-end pancreatojejunostomy, Group 2 end-to-side pancreatojejunostomy with duct-to-mucosa anastomosis, Group 3 end to-side pancreatogastrostomy. RESULTS: Twenty-one % of patients developed POPF, 16% in Group 1, 27% in Group 2, 12% in Group 3. Forty % grade A, 13% grade B and 47% grade C total POPF. It results that POPF occurred in 16% of hard and in 40% of soft pancreatic texture; in 11.4% of dilated Wirsung versus 30.8% of non dilated (p = 0.007). Overall actuarial 1 and 3 year survival after PD is 69% and 48% respectively. Perioperative mortality is 5.8% overall, 17.85% for grade C. CONCLUSIONS: No differences have been found among surgical anastomosis techniques. Soft tissues seem to increase, while dilated Wirsung seems to decrease POPF rate. The development of POPF increase morbidity but it doesn't affect overall survival, more strictly related to tumour histopathology. PMID- 26158176 TI - Laparoscopy-Assisted Distal Gastrectomy for the Eldest Elderly Patients with Gastric Cancer. AB - BACKGROUND/AIMS: The number of the eldest elderly (aged 85 years and older) patients with gastric cancer has been rising in Japan. Laparoscopy-assisted distal gastrectomy (LADG) has been accepted as a less invasive treatment for gastric cancer. The purpose of this study is to evaluate the efficacy and safety of LADG for eldest elderly patents. METHODOLOGY: From January 2006 to July 2010, 262 patients underwent LADG for gastric cancer. Of these, 9 patients were 85 years old and over (eldest elderly group) and the remaining 253 patients were younger than 85 years (control group). Clinicopathological characteristics and operative outcomes were analyzed. RESULTS: Among clinicopathological characteristics analyzed in this study (gender, body mass index, co-morbidity, American Society of Anesthesiologists physical status and tumor status), only gender showed a significant difference between the eldest elderly and the control groups. There were no significant differences in operation time, blood loss, postoperative complication and postoperative hospital stay between the 2 groups. No serious complications or mortality were found in the eldest elderly group. CONCLUSIONS: It is suggested that LADG is a safe and efficient procedure for the treatment of gastric cancer, even in eldest elderly patients. PMID- 26158177 TI - Lin28 Mediates Cancer Chemotherapy Resistance via Regulation of miRNA Signaling. AB - Chemotherapy resistance is one of the major obstacles limiting the success of cancer drug treatment. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to P-Glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. Lin28 is a highly conserved RNA-binding protein, it consists of a cold shock domain and retroviral-type (CCHC) zinc finger motifs. In previous preclinical and clinical studies, positive Lin28 expression in cancer cells was correlated with decreased sensitivity to chemotherapy. And Lin28 could mediate cancer chemotherapy resistance via regulation of miR107 and Let-7 MiRNA. This article reviews current knowledge on predictive value of Lin28 in response to chemotherapy. Better understanding of its role may facilitate patient's selection of therapeutic regimen and lead to optimal clinical outcome. PMID- 26158178 TI - Effect of Combined General/Epidural Anesthesia on Postoperative NK Cell Activity and Cytokine Response in Gastric Cancer Patients Undergoing Radical Resection. AB - BACKGROUND/AIMS: Emerging evidence has shown that epidural anesthesia could reduce the excessive stress response after surgery, and may help to preserve the body's defenses against tumor progression in comparison with general anesthesia in malignant patients receiving operation. This study aims to evaluate the effect of epidural anesthesia on postoperative immune suppression in gastric cancer patients undergoing radical resection. METHODOLOGY: Seventy one gastric cancer patients receiving radical resection were randomized to combined general/epidural anesthesia (study group) or general anesthesia alone (control group). Natural killer cell activity and serum concentrations of protumorigenic cytokines IL 1beta and IL-6, and antitumorigenic cytokines IL-2 and IL-10 were measured before anesthesia (T1), 4h after skin incision (T2), and 24h after skin incision (T3) in both groups. RESULTS: In both groups, the concentrations of IL-10, IL-6, and IL 10 increased at T2 and T3 when compared with T1, whereas IL-2 concentration and NK cell activity decreased at T2 and T3. Furthermore, the study group exhibited less suppression of NK cell activity, higher levels of IL-2 and IL-10, and lower levels of IL-1beta and IL-6 in the early stage after operation, compared with the control group. CONCLUSIOns: Combined general/epidural anesthesia seems to helpful to maintain the body's perioperative immune function compared to general anesthesia alone in patients with gastric cancer operation. PMID- 26158179 TI - Pattern, Timing and Survival in Patients with Recurrent Gastric Cancer. AB - BACKGROUND/AIMS: The aim of this study was to investigate the recurrence patterns, the timing of recurrence, and the survival rate in recurrent cases of gastric cancer. METHODOLOGY: Of 1,029 patients who underwent curative resection for gastric cancer at the Department of Surgery, Korea University Guro Hospital between 2000 and 2006, 146 patients developed recurrence and were included in this study. Timing and patterns of recurrence, the recurrence pattern according to clinicopathological factors, and post-recurrence survival rate were analyzed retrospectively. RESULTS: The mean time to recurrence was 21.2 months. Forty-two patients (28.8%) had recurrence within 1 year, and 54 patients (37.0%) had recurrence 1-2 years after surgery. Single-site recurrence occurred in 72.6% of patients, and multiple-site recurrence in 27.4%. The most frequent pattern of recurrence was peritoneal recurrence in 39.7% of patients, hematogeneous in 24.7%, locoregional in 18.5%, and to a distant lymph node in 17.1%. In cases that showed recurrence within 1 year, the most frequent pattern of recurrence was hematogeneous recurrence, while it was peritoneal in the group with recurrence between 1 and 2 years after surgery. Patterns of recurrence significantly differed according to the sex and gross tumor morphology. The mean post recurrence survival time was 15.7 months. There was no statistically significant difference in the post-recurrence survival time according to the pattern of recurrence. CONCLUSIONS: The most frequent pattern of recurrence was peritoneal recurrence, and recurrence most often occurred within 2 years after curative resection. There was no significant difference in post-recurrence survival time according to the pattern of recurrence. PMID- 26158180 TI - Correlation between Vascular Endothelial Growth Factor and Somatostatin Receptor with Progression and Prognosis in Gastric Cancer. AB - BACKGROUND/AIMS: To investigate the expression of vascular endothelial growth factor (VEGF) and somatostatin receptor (SSTR) and their clinicopathological and prognostic value in gastric cancer (GC). METHODOLOGY: The expression of VEGF and SSTR in 107 cases of GC tissue and 30 cases of gastric mucosa were detected by immunohistochemistry. Clinicopathological and prognostic association of VEGF and SSTR in GC was analyzed RESULTS: The expression of VEGF in GC (70.1%) was significantly higher than that in gastric mucosa (20.0%) The expression of SSTR in GC (62.6%) was significantly lower than that in normal tissues (93.3%). VEGF and SSTR expression were both associated with histological differentiation, depth of invasion, TNM stage, and lymph node metastasis (P < 0.05). The negative expression of VEGF or the positive expression of SSTR was correlated with better overall survival of GC patients. The Cox analysis demonstrated that the expression of VEGF and SSTR, pathological type, TNM stage, and lymph node metastasis were the independent predictors for overall survival in GC (P = 0.005, P = 0.006, P = 0.003, P = 0.002, and P = 0.001, respectively). CONCLUSIONS: The expression of VEGF and SSTR were associated with progression and prognosis of GC. PMID- 26158181 TI - PCF Chemotherapy Combined with Surgical Treatment of Late Gastric Cancer. AB - BACKGROUND/AIMS: To investigate the efficacy and safety of PCF chemotherapy combined with surgery in the treatment of late-stage gastric cancer. METHODOLOGY: From July 2008 to February 2011, 72 cases of late-stage gastric cancer that could not be treated with R0 resection were treated prospectively. Patients received 2 4 cycles of paclitaxel plus cisplatin and 5-fluorouracil (PCF regimen) chemotherapy followed by cytoreductive surgery for the primary and metastatic tumors and another 2-4 cycles of PCF chemotherapy post-operatively. The treatment completion rate, patient tolerance and overall survival time were analyzed. RESULTS: There was one perioperative death. The overall response rate (complete and partial response) was 72.2%. Fifty patients (69.4%) completed chemotherapy and surgical resection as planned and 42 (58.3%) cases had R0 resection. The median survival time was 23.5 months (95% CI: 15.8-31.2 months). One-year and 2 year survival rates were 67.0% and 47.0%. The survival time of patients with surgical resection was much longer than that of the non-surgery group (30.2 vs. 8.9 months) (P < 0.01). The survival time of local advanced group was 30.3 months, and was significantly longer than 17.6 months of the distant metastasis group (P < 0.01); however, it had no significant difference compared to 28.2 months of the distant metastasis group with R0 resection. CONCLUSIONS: PCF chemotherapy combined with surgical resection were safe and effective, and can make survival benefits for some late-stage gastric cancer patients. PMID- 26158193 TI - Primary pyogenic spinal epidural abscess: How late is too late and how bad is too bad? - A study on surgical outcome after delayed presentation. AB - Spinal epidural abscess is a rare clinical entity with considerable morbidity. Even with prompt diagnosis and treatment, many patients are left with persistent residual neurological deficits. The present study details the outcome in 23 patients of primary pyogenic spinal epidural abscess, addressing the outcome following late presentation at a neurological facility. At presentation only 2 patients had relatively preserved neurological status. Eleven patients were paraplegic. All the patients underwent laminectomy and evacuation of abscess. A good functional outcome was observed in almost half of the patients, and there was a significant reduction in the number of the patients with severe disability. Factors influencing the outcome are described in this study. PMID- 26158195 TI - The relationship between lower-limb strength and match-related muscle damage in elite level professional European soccer players. AB - In professional soccer, the benefits of lower limb strength training have been advocated. However, from an aspect of performance development, specifically with respect to expression of fatigue and injury prevention, the advantages of increased lower body strength have received limited attention at the elite level of the game. The primary aim of this cross-sectional investigation was to examine the association between lower body strength and the expression of markers of fatigue as evaluated through muscle damage assessment following match play in professional soccer players. Ten male professional soccer players participated in this investigation (mean +/- SD age 26.2 +/- 4.3 years, height 181.6 +/- 4.8 cm and body mass 78.7 +/- 6.1 kg); creatine kinase (CK) was collected 2-days post match for a 5-month period and at three different time points (Phase 1, Phase 2 and Phase 3); muscular strength (e.g. 4 repetition half-squat) was measured 3-day post-match. No significant change in CK and muscular force across three time points was found (F = 0.60, P = 0.56, eta(2) = 0.06 and F = 2.65, P = 0.10, eta(2) = 0.23, respectively). Muscular force was negatively correlated (moderate to very large) with CK. It can be concluded that players who produce greater lower body force as a result of being stronger in the lower limbs show reduced levels of CK 48 h post-match. PMID- 26158194 TI - Insights into the nuclear export of murine leukemia virus intron-containing RNA. AB - The retroviral genome consists of an intron-containing transcript that has essential cytoplasmic functions in the infected cell. This viral transcript can escape splicing, circumvent the nuclear checkpoint mechanisms and be transported to the cytoplasm by hijacking the host machinery. Once in the cytoplasm, viral unspliced RNA acts as mRNA to be translated and as genomic RNA to be packaged into nascent viruses. The murine leukemia virus (MLV) is among the first retroviruses discovered and is classified as simple Retroviridae due to its minimal encoding capacity. The oncogenic and transduction abilities of MLV are extensively studied, whereas surprisingly the crucial step of its nuclear export has remained unsolved until 2014. Recent work has revealed the recruitment by MLV of the cellular NXF1/Tap-dependent pathway for export. Unconventionally, MLV uses of Tap to export both spliced and unspliced viral RNAs. Unlike other retroviruses, MLV does not harbor a unique RNA signal for export. Indeed, multiple sequences throughout the MLV genome appear to promote export of the unspliced MLV RNA. We review here the current understanding of the export mechanism and highlight the determinants that influence MLV export. As the molecular mechanism of MLV export is elucidated, we will gain insight into the contribution of the export pathway to the cytoplasmic fate of the viral RNA. PMID- 26158196 TI - Dithiophene-TTF Salts; New Ladder Structures and Spin-Ladder Behavior. AB - (alpha-DT-TTF)2[Au(i-mnt)2] and (alpha-DT-TTF)2[Co(mnt)2] are two new salts of the donor alpha-dithiophene-tetrathiafulvalene with stable diamagnetic anions, both presenting a ladder structure of the donors organized in paired segregated stacks. The first one is isostructural with previously reported closely related compounds and presents a magnetic spin-ladder behavior with J?= 83.5 K and J? = 110.3 K as estimated from spin susceptibility data in single crystals. (alpha-DT TTF)2[Co(mnt)2] presents a new structural type with a different arrangement of pairs of donor stacks, alternating with stacks of dimerized [Co(mnt)2] anions which are however arranged in an uncorrelated fashion perpendicular to the stacking axis. Due to the strong coupling between the disordered anion chains and the donor chains, this compound does not present a magnetic spin-ladder behavior. The low temperature superstructure of (DT-TTF)2[Cu(mnt)2] below the transition at 235 K, previously known to be associated with a lattice doubling along the stacking axis, was solved by synchrotron radiation diffraction in small single crystals. It is found that this dimerization is due to donor charge localization with the spin carriers being associated with fully oxidized donor species alternating with neutral donors. PMID- 26158197 TI - Improving f-element single molecule magnets. AB - Ever since the discovery that certain manganese clusters retain their magnetisation for months at low temperatures, there has been intense interest in molecular nanomagnets because of potential applications in data storage, spintronics, quantum computing, and magnetocaloric cooling. In this Tutorial Review, we summarise some key historical developments, and centre our discussion principally on the increasing trend to exploit the large magnetic moments and anisotropies of f-element ions. We focus on the important theme of strategies to improve these systems with the ultimate aim of developing materials for ultra high-density data storage devices. We present a critical discussion of key parameters to be optimised, as well as of experimental and theoretical techniques to be used to this end. PMID- 26158198 TI - Unsymmetrical Diarylmethanes by Ferroceniumboronic Acid Catalyzed Direct Friedel Crafts Reactions with Deactivated Benzylic Alcohols: Enhanced Reactivity due to Ion-Pairing Effects. AB - The development of general and more atom-economical catalytic processes for Friedel-Crafts alkylations of unactivated arenes is an important objective of interest for the production of pharmaceuticals and commodity chemicals. Ferroceniumboronic acid hexafluoroantimonate salt (1) was identified as a superior air- and moisture-tolerant catalyst for direct Friedel-Crafts alkylations of a variety of slightly activated and neutral arenes with stable and readily available primary and secondary benzylic alcohols. Compared to the use of classical metal-catalyzed alkylations with toxic benzylic halides, this methodology employs exceptionally mild conditions to provide a wide variety of unsymmetrical diarylmethanes and other 1,1-diarylalkane products in high yield with good to high regioselectivity. The optimal method, using the bench-stable ferroceniumboronic acid salt 1 in hexafluoroisopropanol as cosolvent, displays a broader scope compared to previously reported catalysts for similar Friedel Crafts reactions of benzylic alcohols, including other boronic acids such as 2,3,4,5-tetrafluorophenylboronic acid. The efficacy of the new boronic acid catalyst was confirmed by its ability to activate primary benzylic alcohols functionalized with destabilizing electron-withdrawing groups like halides, carboxyesters, and nitro substituents. Arene benzylation was demonstrated on a gram scale at up to 1 M concentration with catalyst recovery. Mechanistic studies point toward the importance of the ionic nature of the catalyst and suggest that factors other than the Lewis acidity (pKa) of the boronic acid are at play. A SN1 mechanism is proposed where ion exchange within the initial boronate anion affords a more reactive carbocation paired with the non-nucleophilic hexafluoroantimonate counteranion. PMID- 26158199 TI - Exploring MicroRNA Expression Profiles Related to the mTOR Signaling Pathway in Mouse Embryonic Fibroblast Cells Treated with Polyethylenimine. AB - Although the toxicology of poly(ethylenimine) (PEI) in gene expression levels has been previously investigated, little is known about the effects of PEI on the expression of microRNAs (miRNAs) that regulate gene expression at the post transcriptional level. In this study, we explored miRNA expression profiles related to cell death mechanisms in mouse embryonic fibroblast (MEF) cells treated with PEI by applying microarray analysis. Based on the analysis of the mTOR signaling pathway, three upregulated miRNAs (mmu-miR-3090-5p, mmu-miR-346 3p, and mmu-miR-494-3p) were verified in MEF cells treated with PEI at 24 h using real-time quantitative reverse transcriptase-polymerase chain reaction. We further demonstrated that these three upregulated miRNAs resulted in the decrease of gene and protein expressions of the target gene growth factor Igf1 in MEF cells treated with PEI or transfected with three upregulated miRNA mimics. However, these three upregulated miRNAs are not all cell-specific. Finally, we demonstrated that the mTOR signaling pathway is inhibited by autophagy induction and that the cell viability decreases in MEF cells treated with PEI or transfected with these three miRNA mimics. Collectively, our data suggested that PEI may affect the regulation of miRNAs in target cells. PMID- 26158200 TI - Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers. AB - Hypocholesterolemia has been epidemiologically identified as one of the causes of stroke (cerebral hemorrhage). We previously reported that lower protein levels of mevalonate pyrophosphate decarboxylase (MPD), which is responsible for reducing serum cholesterol levels in stroke-prone spontaneously hypertensive rats (SHRSP), in the liver were caused by a reduction in mRNA levels. However, the mechanism responsible for reducing MPD expression levels in the SHRSP liver remains unclear. Thus, we compared microRNA (miR)-214 combined with the 3'-untranslated region of MPD mRNA and heterogeneous nuclear RNA (hnRNA) between SHRSP and normotensive Wistar Kyoto rats (WKY). miR-214 levels in the liver were markedly higher in SHRSP than in WKY, whereas hnRNA levels were significantly lower. These results indicate that the upregulation of miR-214 and downregulation of MPD transcription in the liver both play a role in the development of hypocholesterolemia in SHRSP. PMID- 26158204 TI - Elevated Concentrations of U and Co-occurring Metals in Abandoned Mine Wastes in a Northeastern Arizona Native American Community. AB - The chemical interactions of U and co-occurring metals in abandoned mine wastes in a Native American community in northeastern Arizona were investigated using spectroscopy, microscopy and aqueous chemistry. The concentrations of U (67-169 MUg L(-1)) in spring water samples exceed the EPA maximum contaminant limit of 30 MUg L(-1). Elevated U (6,614 mg kg(-1)), V (15,814 mg kg(-1)), and As (40 mg kg( 1)) concentrations were detected in mine waste solids. Spectroscopy (XPS and XANES) solid analyses identified U (VI), As (-I and III) and Fe (II, III). Linear correlations for the release of U vs V and As vs Fe were observed for batch experiments when reacting mine waste solids with 10 mM ascorbic acid (~pH 3.8) after 264 h. The release of U, V, As, and Fe was at least 4-fold lower after reaction with 10 mM bicarbonate (~pH 8.3). These results suggest that U-V mineral phases similar to carnotite [K2(UO2)2V2O8] and As-Fe-bearing phases control the availability of U and As in these abandoned mine wastes. Elevated concentrations of metals are of concern due to human exposure pathways and exposure of livestock currently ingesting water in the area. This study contributes to understanding the occurrence and mobility of metals in communities located close to abandoned mine waste sites. PMID- 26158205 TI - Dry-Surface Simulation Method for the Determination of the Work of Adhesion of Solid-Liquid Interfaces. AB - We introduce a methodology, referred to as the dry-surface method, to calculate the work of adhesion of heterogeneous solid-liquid interfaces by molecular simulation. This method employs a straightforward thermodynamic integration approach to calculate the work of adhesion as the reversible work to turn off the attractive part of the actual solid-liquid interaction potential. It is formulated in such a way that it may be used either to evaluate the ability of force fields to reproduce reference values of the work of adhesion or to optimize force-field parameters with reference values of the work of adhesion as target quantities. The methodology is tested in the case of water on a generic model of nonpolar substrates with the structure of gold. It is validated through a quantitative comparison to phantom-wall calculations and against a previous characterization of the thermodynamics of the gold-water interface. It is found that the work of adhesion of water on nonpolar substrates is a nonlinear function of the microscopic solid-liquid interaction energy parameter. We also comment on the ability of mean-field approaches to predict the work of adhesion of water on nonpolar substrates. In addition, we discuss in detail the information on the solid-liquid interfacial thermodynamics delivered by the phantom-wall approach. We show that phantom-wall calculations yield the solid-liquid interfacial tension relative to the solid surface tension rather than the absolute solid-liquid interfacial tension as previously believed. PMID- 26158206 TI - The Use of Liprotides To Stabilize and Transport Hydrophobic Molecules. AB - Recently, it has been shown that different complexes consisting of protein and fatty acids, which we call liprotides, have common functional and structural features. Liprotides can transfer their fatty acid content to membranes, highlighting the potential to incorporate other small molecules and help transfer them to membranes. In this study, this potential was explored with regard to the poorly water-soluble vitamin E compound alpha-tocopherol (Toc). Uptake into liprotides increased Toc solubility and chemical stability. The liprotide-Toc complexes retained the characteristic liprotide structure with a core of fatty acid surrounded by protein. Toc and fatty acid could be transferred to artificial vesicles upon being incorporated into the liprotide complex. Extending this work, we found that free tryptophan and the vitamin A precursor retinaldehyde could also be incorporated in the liprotides; however, other small molecules failed to be taken up, and we conclude that successful incorporation requires a hydrophobic terminal moiety that can be accommodated within the micelle interior of the liprotides. Nevertheless, our work suggests that liprotides are able to stabilize and transport a number of otherwise insoluble small molecules with significant potential health benefits. PMID- 26158207 TI - A Straightforward Approach toward Multifunctionalized Pyridazines via Imination/Electrocyclization. AB - A facile synthesis of functionalized 3-carbamide pyridazines starting from readily available chlorovinyl aldehydes and oxamic acid thiohydrazides via cascade imination/electrocyclization is reported. In the presence of p toluenesulfuric acid, various ketones have been efficiently incorporated into the pyridazine derivatives through a two-step sequence involving a Vilsmeier-Haack reaction and imination. The synthetic value of this method has been demonstrated by efficient synthesis of steroidal pyridazines. PMID- 26158208 TI - Accumulation of Phenylpropanoids by White, Blue, and Red Light Irradiation and Their Organ-Specific Distribution in Chinese Cabbage (Brassica rapa ssp. pekinensis). AB - This study investigated optimum light conditions for enhancing phenylpropanoid biosynthesis and the distribution of phenylpropanoids in organs of Chinese cabbage (Brassica rapa ssp. pekinensis). Blue light caused a high accumulation of most phenolic compounds, including p-hydroxybenzoic acid, ferulic acid, quercetin, and kaempferol, at 12 days after irradiation (DAI). This increase was coincident with a noticeable increase in expression levels of BrF3H, BrF3'H, BrFLS, and BrDFR. Red light led to the highest ferulic acid content at 12 DAI and to elevated expression of the corresponding genes during the early stages of irradiation. White light induced the highest accumulation of kaempferol and increased expression of BrPAL and BrDFR at 9 DAI. The phenylpropanoid content analysis in different organs revealed organ-specific accumulation of p hydroxybenzoic acid, quercetin, and kaempferol. These results demonstrate that blue light is effective at increasing phenylpropanoid biosynthesis in Chinese cabbage, with leaves and flowers representing the most suitable organs for the production of specific phenylpropanoids. PMID- 26158209 TI - Enhancement of the antibiotic activity of aminoglycosides by extracts from Anadenanthera colubrine (Vell.) Brenan var. cebil against multi-drug resistant bacteria. AB - The aim of this work was to evaluate the antimicrobial activity of ethanol (EEAC) and hexane (HFAC) extracts from the stem bark of Anadenanthera colubrina (Vell.) Brenan var. cebil alone or in combination with aminoglycosides against multi-drug resistant (MDR) bacteria. Minimal inhibitory concentrations (MICs) of the extracts were determined by using microdilution assay. For the evaluation of extracts as modulators of antibiotic resistance, MICs of neomycin and amikacin were determined in presence or absence of each compound at sub-inhibitory concentrations. Both EEAC and HFAC did not show antimicrobial activity against MDR strains tested. However, the addition of EEAC and HFAC enhanced the activity of neomycin and amikacin against Staphylococcus aureus SA10 strain. When the natural products were replaced by chlorpromazine, the same effect was observed. Anadenanthera colubrine var. cebil may be a source of phytochemicals able to potentiate the aminoglycoside activity against MDR S. aureus by the inhibition of efflux pump. PMID- 26158210 TI - Numerical simulation of peristaltic flow of a biorheological fluid with shear dependent viscosity in a curved channel. AB - Peristaltic motion of a non-Newtonian Carreau fluid is analyzed in a curved channel under the long wavelength and low Reynolds number assumptions, as a simulation of digestive transport. The flow regime is shown to be governed by a dimensionless fourth-order, nonlinear, ordinary differential equation subject to no-slip wall boundary conditions. A well-tested finite difference method based on an iterative scheme is employed for the solution of the boundary value problem. The important phenomena of pumping and trapping associated with the peristaltic motion are investigated for various values of rheological parameters of Carreau fluid and curvature of the channel. An increase in Weissenberg number is found to generate a small eddy in the vicinity of the lower wall of the channel, which is enhanced with further increase in Weissenberg number. For shear-thinning bio fluids (power-law rheological index, n < 1) greater Weissenberg number displaces the maximum velocity toward the upper wall. For shear-thickening bio-fluids, the velocity amplitude is enhanced markedly with increasing Weissenberg number. PMID- 26158211 TI - The Chernobyl accident, the male to female ratio at birth and birth rates. PMID- 26158212 TI - Patterns of Intimate Partner Violence and Sexual Risk Behavior among Young Heterosexually Active Men. AB - Intimate partner violence (IPV) victimization is linked to sexual risk exposure among women. However, less is known about the intersection of IPV perpetration and sexual risk behavior among men. This study used data from a diverse, community sample of 334 heterosexually active young men, aged 18 to 25, across the United States to examine whether and how men with distinct IPV-related behavior patterns differed in sexual risk-related behavior and attitudes. Participants were recruited and surveyed online, and grouped conceptually based on the types of IPV perpetration behavior(s) used in a current or recent romantic relationship. Groups were then compared on relevant sexual risk variables. Men reporting both physical abuse and sexual coercion against intimate partners reported significantly higher numbers of lifetime partners, higher rates of nonmonogamy, greater endorsement of nonmonogamy, and less frequent condom use relative to nonabusive men or those reporting controlling behavior only. This group also had higher sexually transmitted infection (STI) exposure compared to men who used controlling behavior only and men who used sexual coercion only. Findings suggest that interventions with men who use physical and sexual violence need to account for not only the physical and psychological harm of this behavior but also the sexual risk to which men may expose their partners. PMID- 26158215 TI - Radiolabeled gastrin/CCK analogs in tumor diagnosis: towards higher stability and improved tumor targeting. AB - Cholecystokinin subtype 2 receptors (CCK2R) are overexpressed in several human cancers, including medullary thyroid carcinoma. Gastrin and cholecystokinin (CCK) peptides that bind with high affinity and specificity to CCK2R can be used as carriers of radioactivity to CCK2R-expressing tumor sites. Several gastrin and CCK related peptides have been proposed for diagnostic imaging and radionuclide therapy of primary and metastatic CCK2R-positive human tumors. Their clinical application has been restricted to a great extent by their fast in vivo degradation that eventually compromises tumor uptake. This problem has been addressed by structural modifications of gastrin and CCK motifs, which, however, often lead to suboptimal pharmacokinetic profiles. A major enzyme implicated in the catabolism of gastrin and CCK based peptides is neutral endopeptidase (NEP), which is widely distributed in the body. Coinjection of the NEP inhibitor phosphoramidon (PA) with radiolabeled gastrin and other peptide analogs has been recently proposed as a new promising strategy to increase bioavailability and tumor-localization of radiopeptides in tumor sites. Specifically, co administration of PA with the truncated gastrin analog [(111)In-DOTA]MG11 ([((111)In-DOTA)DGlu(10)]gastrin(10-17)) impressively enhanced the levels of intact radiopeptide in mouse circulation and has led to an 8-fold increase of CCK2R-positive tumor uptake in SCID mice. This increased tumor uptake, visualized also by SPECT/CT imaging, is expected to eventually translate into higher diagnostic sensitivity and improved therapeutic efficacy of radiolabeled gastrin analogs in CCK2R-expressing cancer patients. PMID- 26158217 TI - Sexual selection and cancer biology. PMID- 26158216 TI - Neutrophils trigger a NF-kappaB dependent polarization of tumor-supportive stromal cells in germinal center B-cell lymphomas. AB - Both tumor-associated neutrophils (TAN) and cancer-associated fibroblasts (CAFs) display specific phenotypic and functional features and contribute to tumor cell niche. However, their bidirectional crosstalk has been poorly studied, in particular in the context of hematological malignancies. Follicular lymphomas (FL) and diffuse large B-cell lymphomas (DLBCL) are two germinal center-derived lymphomas where various cell components of infiltrating microenvironment, including TAN and CAFs, have been demonstrated to favor directly and indirectly malignant B-cell survival, growth, and drug resistance. We show here that, besides a direct and contact-dependent supportive effect of neutrophils on DLBCL B-cell survival, mediated through the BAFF/APRIL pathway, neutrophils and stromal cells cooperate to sustain FL B-cell growth. This cooperation relies on an overexpression of IL-8 by lymphoma-infiltrating stromal cells that could thereafter efficiently promote neutrophil survival and prime them to neutrophil extracellular trap. Conversely, neutrophils are able to activate stromal cells in a NF-kappaB-dependent manner, inducing their commitment towards an inflammatory lymphoid stroma phenotype associated with an increased capacity to trigger malignant B-cell survival, and to recruit additional monocytes and neutrophils through the release of CCL2 and IL-8, respectively. Altogether, a better understanding of the lymphoma-supporting effects of neutrophils could be helpful to design new anti-tumor therapeutic strategies. PMID- 26158219 TI - Lindqvist Polyoxoniobate Ion-Assisted Electrodeposition of Cobalt and Nickel Water Oxidation Catalysts. AB - A method has been developed for the efficient electrodeposition of cobalt and nickel nanostructures with the assistance of the Lindqvist ion [Nb6O19](8-). Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Raman spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), inductively coupled plasma optical emission spectrometry, and a range of electrochemical techniques have been used to characterize the morphology, composition, catalytic water oxidation activity and stability of the films in alkaline solution. SEM images show that films consisting of nanoparticles with diameters of ca. 30 to 40 nm are formed after 40-50 potential cycles of deposition. Nb and Co/Ni are detected in the films by EDX. ICP-MS results show an elemental ratio of 1:1 for Co:Nb and 1:3 for Ni:Nb, respectively. Raman spectra reveal the presence of both [Nb6O19](8-) and Co(OH)2/Ni(OH)2. The films exhibit excellent stability and efficiency for electrocatalytic water oxidation in alkaline solution. Turnover frequencies of 12.9 and 13.2 s(-1) were determined by rotating ring disk electrode voltammetry at an overpotential of 480 mV for Co and Ni films, respectively. Fourier transformed large amplitude alternating current (FTAC) voltammetry reveals an additional underlying oxidation process for Co under catalytic turnover conditions, which indicates that a Co(IV) species is involved in the efficient catalytic water oxidation reactions. FTAC voltammetric data also suggest that the Ni films undergoes a clear phase transformation upon aging in aqueous 1 M NaOH and the electrogenerated higher oxidation state Ni from beta-NiOOH is the more active form of the catalyst. PMID- 26158220 TI - Diurnal modulation of visual motion prediction. AB - Predicting the future position of moving objects is an essential cognitive function used for many daily activities, such as driving, walking and reaching. The experiments described in this paper show a marked diurnal modulation of motion prediction in inflating image perception. This motion prediction was shown to be more accurate in the afternoon than in the morning. In contrast, such modulation could not be found in deflating image perception. Such diurnal fluctuations may be mediated by circadian properties of retinal cone photoreceptors. PMID- 26158218 TI - Oncogenic cancer/testis antigens: prime candidates for immunotherapy. AB - Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer/testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic functions, including support of growth, survival and metastasis. This novel insight into the function of cancer/testis antigens has the potential to deliver more effective cancer vaccines. Moreover, immune targeting of oncogenic cancer/testis antigens in combination with conventional cytotoxic therapies or novel immunotherapies such as checkpoint blockade or adoptive transfer, represents a highly synergistic approach with the potential to improve patient survival. PMID- 26158221 TI - Ubiquitous healthy diatoms in the deep sea confirm deep carbon injection by the biological pump. AB - The role of the ocean as a sink for CO2 is partially dependent on the downward transport of phytoplankton cells packaged within fast-sinking particles. However, whether such fast-sinking mechanisms deliver fresh organic carbon down to the deep bathypelagic sea and whether this mechanism is prevalent across the ocean requires confirmation. Here we report the ubiquitous presence of healthy photosynthetic cells, dominated by diatoms, down to 4,000 m in the deep dark ocean. Decay experiments with surface phytoplankton suggested that the large proportion (18%) of healthy photosynthetic cells observed, on average, in the dark ocean, requires transport times from a few days to a few weeks, corresponding to sinking rates (124-732 m d(-1)) comparable to those of fast sinking aggregates and faecal pellets. These results confirm the expectation that fast-sinking mechanisms inject fresh organic carbon into the deep sea and that this is a prevalent process operating across the global oligotrophic ocean. PMID- 26158222 TI - Insights into the effects of metal nanostructuring and oxidation on the work function and charge transfer of metal/graphene hybrids. AB - Graphene/metal heterojunctions are ubiquitous in graphene-based devices and, therefore, have attracted increasing interest of researchers. Indeed, the literature on the field reports apparently contradictory results about the effect of a metal on graphene doping. Here, we elucidate the effect of metal nanostructuring and oxidation on the metal work function (WF) and, consequently, on the charge transfer and doping of graphene/metal hybrids. We show that nanostructuring and oxidation of metals provide a valid support to frame WF and doping variation in metal/graphene hybrids. Chemical vapour-deposited monolayer graphene has been transferred onto a variety of metal surfaces, including d metals, such as Ag, Au, and Cu, and sp-metals, such as Al and Ga, configured as thin films or nanoparticle (NP) ensembles of various average sizes. The metal induced charge transfer and the doping of graphene have been investigated using Kelvin probe force microscopy (KPFM), and corroborated by Raman spectroscopy and plasmonic ellipsometric spectroscopy. We show that when the appropriate WF of the metal is considered, without any assumption, taking into account WF variations by nanostructure and/or oxidation, a linear relationship between the metal WF and the doping of graphene is found. Specifically, for all metals, nanostructuring lowers the metal WF. In addition, using gold as an example, a critical metal nanoparticle size is found at which the direction of charge transfer, and consequently graphene doping, is inverted. PMID- 26158223 TI - Effect of 5-caffeoylquinic acid on the NF-kappaB signaling pathway, peroxisome proliferator-activated receptor gamma 2, and macrophage infiltration in high-fat diet-fed Sprague-Dawley rat adipose tissue. AB - Obesity, considered as a consequence of overnutrition, sustains a low-degree inflammatory state and results in insulin-resistance and type 2 diabetes. Here, we investigated the anti-inflammatory effects of 5-caffeoylquinic acid (5-CQA) in high-fat diet-induced obese rats. Serum interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) levels were determined. Expression of genes related to TG metabolism, macrophage biomarkers, and inflammation was assessed by real-time PCR. Protein expression of NF-kappaB, PPARgamma2, and phosphorylated IkappaBalpha was evaluated by western blotting, and the histology of adipose tissue was examined. Supplementation of the rat diet with 5-CQA reduced obesity development, macrophage infiltration, and steatosis. Additionally, 5-CQA decreased the expression of NF-kappaB and downstream inflammatory cytokines, but increased the expression of PPARgamma2, in a dose dependent manner. Thus, 5-CQA improved obesity and obesity-related metabolic disturbances via PPARgamma2 and the NF-kappaB signaling pathway. PMID- 26158224 TI - Analysis of the Free Energy Landscapes for the Opening-Closing Dynamics of the Maltose Transporter ATPase MalK2 Using Enhanced-Sampling Molecular Dynamics Simulation. AB - Protein dynamics are considered significant for many physiological processes, such as metabolism, biomolecular recognition, and the regulation of several vital cellular processes. Due to their flexibility, proteins may stay in different substates with or without the existence of the cognate substrates. To describe these phenomena, two models have been proposed: the "induced fit" and the "conformational selection" mechanisms. In this study, we used MalK2, the subunits that mainly include the nucleotide-binding domains (NBDs) of the maltose transporter from Escherichia coli, as a target to understand the NBD dimerization mechanism. Accelerated and conventional molecular dynamics have been performed. The results revealed that Mg-ATP binding to MalK2 led to a significant change in the free energy profile and thus stabilized the closed conformation. On the contrary, when Mg-ATP was removed, the open conformation would be favored. The fact that ligand binding induces a drastic free energy change leads to a significant inference: MalK2 dimerization would occur through the induced-fit mechanism rather than the conformational selection mechanism. This study sheds new light on the NBD dimerization mechanism and would be of wide applicability to other ABC transporters. PMID- 26158225 TI - 8th vaccine renaissance: A creative nexus for vaccine developers. PMID- 26158226 TI - Internal Referencing for 13C Position-Specific Isotope Analysis Measured by NMR Spectrometry. AB - The intramolecular (13)C composition of a molecule retains evidence relevant to its (bio)synthetic history and can provide valuable information in numerous fields ranging from biochemistry to environmental sciences. Isotope ratio monitoring by (13)C NMR spectrometry (irm-(13)C NMR) is a generic method that offers the potential to conduct (13)C position-specific isotope analysis with a precision better than 10/00. Until now, determining absolute values also required measurement of the global (or bulk) (13)C composition (delta(13)Cg) by mass spectrometry. In a radical new approach, it is shown that an internal isotopic chemical reference for irm-(13)C NMR can be used instead. The strategy uses (1)H NMR to quantify both the number of moles of the reference and of the studied compound present in the NMR tube. Thus, the sample preparation protocol is greatly simplified, bypassing the previous requirement for precise purity and mass determination. The key to accurate results is suppressing the effect of radiation damping in (1)H NMR which produces signal distortion and alters quantification. The methodology, applied to vanillin with dimethylsulfone as an internal standard, has an equivalent accuracy (<10/00) to that of the conventional approach. Hence, it was possible to clearly identify vanillin from different origins based on the (13)C isotopic profiles. PMID- 26158228 TI - Voices from the past: Mental and physical outcomes described by American Civil War amputees. AB - Studies of trauma commonly concentrate on the psychological and physiological effects of recent violent events. Although today connections are becoming more explicitly drawn, early studies of the aftermath of amputation serve to shed light on modern understanding of the interaction of the physical and emotional. The study of combat amputation, dissociation, and related posttraumatic stress largely began with the work of 19th-century Philadelphia physician Silas Weir Mitchell, who brought attention to the phenomenon of phantom limb pain. Less known, however, are the data he and his son, John K. Mitchell, also collected on the mental outcomes of trauma. Using an archived collection of original surveys of double-amputee patients dating largely from 1893 housed at the Historical Medical Library at the College of Physicians of Philadelphia, an interdisciplinary team explored the historical, anthropological, and psychological background of the study of combat trauma. Almost 30 years following the end of hostilities, the majority of the sample of U.S. Civil War veterans indicated that their general disposition, general health, and sleeping or eating patterns had changed following limb amputation. More telling, possibly, are the written comments on the surveys and letters that indicate frustration with the continuous suffering and the knowledge of their mental and physical changes. These data illustrate the value of historical archives in documenting the development of the study of trauma and modern concepts of combat experiences. PMID- 26158227 TI - A palette of fluorescent proteins optimized for diverse cellular environments. AB - To perform quantitative live cell imaging, investigators require fluorescent reporters that accurately report protein localization and levels, while minimally perturbing the cell. Yet, within the biochemically distinct environments of cellular organelles, popular fluorescent proteins (FPs), including EGFP, can be unreliable for quantitative imaging, resulting in the underestimation of protein levels and incorrect localization. Specifically, within the secretory pathway, significant populations of FPs misfold and fail to fluoresce due to non-native disulphide bond formation. Furthermore, transmembrane FP-fusion constructs can disrupt organelle architecture due to oligomerizing tendencies of numerous common FPs. Here, we describe a powerful set of bright and inert FPs optimized for use in multiple cellular compartments, especially oxidizing environments and biological membranes. Also, we provide new insights into the use of red FPs in the secretory pathway. Our monomeric 'oxFPs' finally resolve long-standing, underappreciated and important problems of cell biology and should be useful for a number of applications. PMID- 26158229 TI - Shift happens: family background influences clinical variability in genetic neurodevelopmental disorders. PMID- 26158230 TI - Is prenatal cytogenetic diagnosis with genomic array indicated in pregnancies at risk for a molecular or metabolic disorder? PMID- 26158231 TI - Composition Directed Generation of Reactive Oxygen Species in Irradiated Mixed Metal Sulfides Correlated with Their Photocatalytic Activities. AB - The ability of nanostructures to facilitate the generation of reactive oxygen species and charge carriers underlies many of their chemical and biological activities. Elucidating which factors are essential and how these influence the production of various active intermediates is fundamental to understanding potential applications of these nanostructures, as well as potential risks. Using electron spin resonance spectroscopy coupled with spin trapping and spin labeling techniques, we assessed 3 mixed metal sulfides of varying compositions for their abilities to generate reactive oxygen species, photogenerate electrons, and consume oxygen during photoirradiation. We found these irradiated mixed metal sulfides exhibited composition dependent generation of ROS: ZnIn2S4 can generate (*)OH, O2(-*) and (1)O2; CdIn2S4 can produce O2(-*) and (1)O2, while AgInS2 only produces O2(-*). Our characterizations of the reactivity of the photogenerated electrons and consumption of dissolved oxygen, performed using spin labeling, showed the same trend in activity: ZnIn2S4 > CdIn2S4 > AgInS2. These intrinsic abilities to generate ROS and the reactivity of charge carriers correlated closely with the photocatalytic degradation and photoassisted antibacterial activities of these nanomaterials. PMID- 26158232 TI - Increased Autophagy Markers Are Associated with Ductular Reaction during the Development of Cirrhosis. AB - Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control. Patients with cirrhotic livers had significantly increased levels of various essential autophagy-related genes compared with noncirrhotic livers. In addition, colocalization of autophagy marker microtubule associated protein 1 light chain 3B (LC3B) with lysosome-associated membrane protein-1, increased levels of lysosome-associated membrane protein-2, and increased maturation of lysosomal cathepsin D were observed in cirrhotic livers. By using dual-immunofluorescence staining, we demonstrated that increased LC3B was located mainly in the cytokeratin 19-labeled ductular reaction (DR) in human cirrhotic livers and in an experimental cirrhosis induced by 2 acetylaminofluorene (AAF) with carbon tetrachloride (CCl4), indicating a conserved response to chronic liver damage. Furthermore, an AAF/CCl4-mediated increase in DR and fibrosis were attenuated after chloroquine treatment, suggesting that the autophagy-lysosome pathway was essential for AAF/CCl4-induced DR-fibrosis. In conclusion, we demonstrated that increased autophagy marker positively correlated with DR during the development of cirrhosis. Therefore, targeting autophagy may hold therapeutic value for liver cirrhosis. PMID- 26158233 TI - Biosynthetic infochemical communication. AB - There is an ever-increasing demand for data to be embedded in our environment at ever-decreasing temporal and spatial scales. Whilst current communication and storage technologies generally exploit the electromagnetic properties of media, chemistry offers us a new alternative for nanoscale signaling using molecules as messengers with high information content. Biological systems effectively overcome the challenges of chemical communication using highly specific biosynthetic pathways for signal generation together with specialized protein receptors and nervous systems. Here we consider a new approach for information transmission based upon nature's quintessential example of infochemical communication, the moth pheromone system. To approach the sensitivity, specificity and versatility of infochemical communication seen in nature, we describe an array of biologically-inspired technologies for the production, transmission, detection, and processing of molecular signals. We show how it is possible to implement each step of the moth pheromone pathway for biosynthesis, transmission, receptor protein binding/transduction, and antennal lobe processing of monomolecular and multimolecular signals. For each implemented step, we discuss the value, current limitations, and challenges for the future development and integration of infochemical communication technologies. Together, these building blocks provide a starting point for future technologies that can utilize programmable emission and detection of multimolecular information for a new and robust means of communicating chemical information. PMID- 26158234 TI - Notice of Retraction: Plagiarism in Win AZ. "Child Farm Laborers." Am J Public Health. 2015;105(7):1312. doi: 10.2105/AJPH.2015.302623. PMID- 26158237 TI - The Social Evil in Relation to the Health Problem. 1913. PMID- 26158238 TI - Information Entropy of Fullerenes. AB - The reasons for the formation of the highly symmetric C60 molecule under nonequilibrium conditions are widely discussed as it dominates over numerous similar fullerene structures. In such conditions, evolution of structure rather than energy defines the processes. We have first studied the diversity of fullerenes in terms of information entropy. Sorting 2079 structures from An Atlas of Fullerenes [ Fowler , P. W. ; Manolopoulos , D. E. An Atlas of Fullerenes ; Oxford : Clarendon , 1995 . ], we have found that the information entropies of only 14 fullerenes (<1% of the studied structures) lie between the values of C60 and C70, the two most abundant fullerenes. Interestingly, buckminsterfullerene is the only fullerene with zero information entropy, i.e., an exclusive compound among the other members of the fullerene family. Such an efficient sorting demonstrates possible relevance of information entropy to chemical processes. For this reason, we have introduced an algorithm for calculating changes in information entropy at chemical transformations. The preliminary calculations of changes in information entropy at the selected fullerene reactions show good agreement with thermochemical data. PMID- 26158240 TI - Iron-Catalyzed Cyclization of Alkynols with Diorganyl Diselenides: Synthesis of 2,5-Dihydrofuran, 3,6-Dihydro-2H-pyran, and 2,5-Dihydro-1H-pyrrole Organoselanyl Derivatives. AB - An iron-catalyzed system, using diorganyl diselenides as an organoselenium source, was used for the cyclization of 1,4-butyne-diols in the preparation of 3,4-bis(organoselanyl)-2,5-dihydrofurans. The optimized reaction conditions are compatible with many functional groups in 1,4-butyne-diols and diorganyl diselenides. In addition, this catalyst system was also efficient with diorganyl disulfides, but it did not work for diorganyl ditellurides. The same reaction conditions were also extended to pentyne-1,5-diol for the preparation of 4,5 bis(organoselanyl)-3,6-dihydro-2H-pyrans and to 4-amino-butynol for the preparation of 2,5-dihydro-1H-pyrrole derivatives. The synthetic utility of these heterocycles was studied using 5-bis(organoselanyl)-3,6-dihydro-2H-pyrans as substrate in a Kumada-type cross-coupling reaction. PMID- 26158241 TI - Treatment of Barrett's esophagus with a novel focal cryoablation device: a safety and feasibility study. AB - BACKGROUND AND AIMS: Currently, eradication of Barrett's epithelium is preferably achieved using radiofrequency ablation (RFA) or spray cryoablation (SCA). However, both modalities suffer from drawbacks such as the need for sizing, multiple deployment steps, large controller units (RFA), imprecise dosing and need for gas-venting (SCA). The new Cryoballoon Focal Ablation System (CbFAS) may address these limitations. This study assessed the safety, feasibility, and dose response of the CbFAS in patients with flat Barrett's epithelium with or without dysplasia. PATIENTS AND METHODS: In this multicenter, prospective non-randomized trial, 39 patients were each treated with one or two ablations of 6, 8, or 10 seconds. Symptoms were assessed immediately and 2 days post-cryoablation. Follow up endoscopy was performed 6-8 weeks post-procedure to assess response. Outcome parameters were incidence of adverse events, pain, esophageal stricture formation, and ablation response by cryogen dose. RESULTS: Of 62 ablations, 56 (10 with 6 seconds, 28 with 8 seconds, 18 with 10 seconds) were successfully performed. Six ablations failed because of device malfunction (n=3) and procedural or anatomic issues (n=3). Median procedure time was 7 minutes (interquartile range [IQR] 4-10). No major adverse events occurred; six patients experienced a minor mucosal laceration requiring no intervention. Mild pain was reported by 27% of patients immediately after cryoablation and by 14% after 2 days. No strictures were evident at follow-up. Full squamous regeneration was seen in 47 treated areas (6 [60%] of the 6-second areas; 23 [82%] of the 8-second areas; 18 [100%] of 10-second areas). CONCLUSIONS: Focal cryoablation of Barrett's epithelium with the CbFAS is feasible and safe, resulting in squamous regeneration in the majority of patients. PMID- 26158242 TI - Diagnostic accuracy of magnification endoscopy with acetic acid enhancement and narrow-band imaging in gastric mucosal neoplasms. AB - BACKGROUND AND STUDY AIMS: Magnification endoscopy with narrow-band imaging (NBIME) and NBIME with acetic acid enhancement (A-NBIME) visualize the capillary and microstructure patterns of the gastric mucosal surface, respectively. This study aimed to compare the diagnostic accuracy and interobserver agreement for white-light endoscopy (WLE), NBIME, and A-NBIME in the different histologic types of gastric mucosal neoplasm. PATIENTS AND METHODS: Consecutive gastric neoplasms (n = 220; 49 adenomas, 144 differentiated adenocarcinomas, and 27 undifferentiated adenocarcinomas) were photographed with WLE, NBIME, and A-NBIME. Macroscopic patterns using WLE, capillary patterns using NBIME, and microstructure patterns using A-NBIME were respectively classified into type M1/M2/M3, type C1/C2/C3/C4, and type S1/S2/S3, as the indicators of adenoma, differentiated adenocarcinoma, and undifferentiated adenocarcinoma (Type C4, unevaluable because of capillary invisibility), according to the previously reported classifications. Endoscopic images were independently reviewed by three experts and three non-experts. Diagnostic accuracy and interobserver diagnostic agreement were compared among the modalities. RESULTS: Kappa values (95 % confidence interval [CI]) for WLE, NBIME, and A-NBIME diagnosis were 0.36 (0.33 - 0.39), 0.58 (0.54 - 0.61), and 0.62 (0.55 - 0.68) for experts and 0.31 (0.29 - 0.33), 0.36 (0.34 - 0.38), and 0.52 (0.48 - 0.56) for non-experts, showing good reproducibility of A-NBIME diagnosis regardless of proficiency. All experts and non-experts diagnosed the histologic types statistically more accurately with A NBIME than with WLE and NBIME (P < 0.05). Overall the "experts-agreed" diagnostic accuracy (95 %CI) was 75.5 % (70.0 - 81.0) for WLE vs. 74.1 % (67.6 - 80.6) for NBIME vs. 90.5 % (86.7 - 94.1) for A-NBIME (P < 0.05). WLE and NBIME were insufficient to predict the diagnosis of adenomas and undifferentiated adenocarcinomas. CONCLUSION: A-NBIME showed statistically significantly higher diagnostic accuracy for gastric mucosal neoplasms, with good reproducibility, compared with WLE and NBIME, which provided similar lower accuracy. PMID- 26158243 TI - Differential response of GnIH in the brain and gonads following acute stress in a songbird. AB - Gonadotropin-inhibitory hormone (GnIH) acts to inhibit reproduction at all levels of the hypothalamo-pituitary-gonad axis. GnIH expression and/or immunoreactivity in the hypothalamus increase with acute stress in some birds and mammals, and thus may be involved in stress-induced reproductive inhibition. Much is known about GnIH and stress in seasonal and continuous breeders, but far less is known about these interactions in opportunistic breeders. For opportunistically breeding animals, reproductive readiness is closely associated with unpredictable environmental cues, and thus the GnIH system may be more sensitive to stress. To test this, we collected tissues from zebra finches immediately following capture or after 60 min of restraint. Restraint significantly increased plasma corticosterone in males and females but, contrary to studies on other species, restrained birds had significantly fewer GnIH immunoreactive (GnIH-ir) cell bodies than control birds. GnIH-ir cell number did not differ between the sexes. Stressed females had lower mRNA expression of the beta subunit of follicle stimulating hormone (FSHbeta) in the pituitary, suggesting that the reduction in observed GnIH immunoreactivity in females may have been due to increased GnIH release in response to acute stress. GnIH expression increased in the testes, but not the ovaries, of restrained animals. Our data suggest that although GnIH responsiveness to stress appears to be conserved across species, specific tissue response and direction of GnIH regulation is not. Variation in the GnIH response to stress between species might be the result of ecological adaptations or other species differences in the response of the GnIH system to stress. PMID- 26158244 TI - Significant radiative impact of volcanic aerosol in the lowermost stratosphere. AB - Despite their potential to slow global warming, until recently, the radiative forcing associated with volcanic aerosols in the lowermost stratosphere (LMS) had not been considered. Here we study volcanic aerosol changes in the stratosphere using lidar measurements from the NASA CALIPSO satellite and aircraft measurements from the IAGOS-CARIBIC observatory. Between 2008 and 2012 volcanism frequently affected the Northern Hemisphere stratosphere aerosol loadings, whereas the Southern Hemisphere generally had loadings close to background conditions. We show that half of the global stratospheric aerosol optical depth following the Kasatochi, Sarychev and Nabro eruptions is attributable to LMS aerosol. On average, 30% of the global stratospheric aerosol optical depth originated in the LMS during the period 2008-2011. On the basis of the two independent, high-resolution measurement methods, we show that the LMS makes an important contribution to the overall volcanic forcing. PMID- 26158245 TI - Delirium and Circadian Rhythm of Melatonin During Weaning From Mechanical Ventilation: An Ancillary Study of a Weaning Trial. AB - BACKGROUND: Delirium is frequent in patients in the ICU, but its association with the outcome of weaning from mechanical ventilation has not been assessed. Circadian rhythm alteration may favor delirium. In the current study, we assessed the impact of delirium during weaning and associated alterations in the circadian rhythm of melatonin excretion. METHODS: This was a substudy of 70 participants of the B-type Natriuretic Peptide for the Fluid Management of Weaning trial, comparing two fluid management strategies during weaning. Patients with or without delirium (as assessed using the Confusion Assessment Method for the ICU) were compared in terms of baseline characteristics and outcomes and the circadian rhythm of melatonin excretion using the 24-h excretion of its urinary metabolite 6-sulfatoxymelatonin (aMT6s). RESULTS: Among the 70 patients included, 43 (61.4%) experienced delirium at the initiation of weaning. Delirium at the initiation of weaning was associated with more alcohol consumption, a greater severity of illness, and medication use before weaning (including neuromuscular blockade, antibiotics, sedatives, and narcotics). Delirium at the initiation of weaning was associated with more respiratory and neurologic complications and a reduced probability of successful extubation (Cox multivariate model hazard ratio of successful extubation = 0.54; 95% CI, 0.30-0.95; P = .03). Delirium was also associated with a significant reduction in peak, mean, amplitude, and total values of aMT6s urinary excretion during the first 24 h of weaning (general linear model F statistic = 5.81, P = .019). CONCLUSIONS: Delirium is frequent at the initiation of ventilator weaning. It is associated with a prolongation of weaning and an alteration in the circadian rhythm of melatonin excretion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00473148; URL: www.clinicaltrials.gov. PMID- 26158247 TI - In Memoriam Madeleine Lejour. PMID- 26158248 TI - The Influence of Intraoperative Factors and Histopathological Staging on the Performance of Sentinel Node Biopsy in Colon Cancer. AB - BACKGROUND: The aim of this study was to assess sentinel node biopsy (SNB) results in colon cancer (CC) regarding intraoperative staging of the disease and pathological cancer features. MATERIAL AND METHODS: The study was conducted on the basis of 132 SNBs in CC. The elements of intraoperative staging of the disease and pathological cancer features were compared with accuracy, sensitivity and false negative results of SNB in CC by means of ROC curves and the tests for population proportions. RESULTS: ROC curve analysis did not reveal any statistical significance for tumour measurements (all p > 0.05). Statistically significantly worse results in sensitivity (not in accuracy) were achieved for T3 tumours in comparison with T2 tumours (83% vs 89%, p = 0.0066). Statistically significantly worse results in accuracy (not in sensitivity) of the method were obtained in the cases of involved lymph nodes (78% vs 100%, p < 0.0001), infiltration of the lymph node capsule (80% vs 97%, p = 0.0023) and infiltration of the perinodal tissue (73% vs 97%, p = 0.0002). The analyses of SNB sensitivity and accuracy in combination with other features showed no statistical significance (all p > 0.05). CONCLUSIONS: The sensitivity of the method is significantly worse for tumours with deeper infiltration of intestinal wall. The presence of nodal metastases, lymph node capsule and perinodal invasion significantly affects the accuracy results of SNB in CC. The problem of qualifying patients for the procedure in regard to the other analysed features, however, remains open and requires further analysis. PMID- 26158249 TI - Long Term Results of Kissing Stents in the Aortic Bifurcation. AB - BACKGROUND: To evaluate the long-term outcome after aortoiliac kissing stent placement and to analyze variables, which potentially influence the outcome of endovascular reconstruction of the aortic bifurcation. METHODS: All patients treated with aortoiliac kissing stents at our institution between April 1995 and August 2011 were retrospectively identified from a prospective single-center database. Data regarding patient characteristics (age, gender, smoking, cardio- and cerebrovascular risk factors, hyperlipidaemia, diabetes mellitus and use of antihypertensive medication), symptoms, pre-interventional examination and imaging, procedural details and follow-up were retrieved. Patency rates were calculated with Kaplan-Meier analysis. Factors affecting the patency were determined with Cox uni- and multivariate analysis. RESULTS: A total of 215 patients (63% men, mean age 61 +/- 10 years) were included. The median follow-up period was 31 (IQR 47.1) months. Primary, primary assisted, and secondary patency rates were 97%, 97%, and 99%, respectively, at one month; 92%, 95% and 94% at four months; 75%, 86%, and 91% at two years; 70%, 81%, and 91% at 5 years; and 67%, 81%, and 91% at ten years. Younger age and previous aortoiliac treatment were predictors for reduced primary and primary assisted patency. Smoking, previous aortoiliac intervention, TASC C and D lesions were predictors for reduced secondary patency. CONCLUSIONS: Reconstruction of the aortoiliac bifurcation with kissing stents is feasible, safe and effective in all types of lesions with satisfying long term patencies. TASC C and D lesions are associated with a higher occlusion rate. Younger age and previous aortoiliac interventions are predictors for reduced primary and primary assisted patency. PMID- 26158250 TI - Total Thyroidectomy for Management of Benign Multinodular Goitre in an Endemic Region: Review of 620 Case. AB - INTRODUCTION: The aim of this study was to evaluate the safety and efficiency of total thyroidectomy (TT) when performed by an experienced surgeon in benign multinodular goitre (BMNG) in an endemic region. MATERIAL AND METHODS: A total of six hundred and twenty consecutive patients, who underwent a total thyroidectomy for BMNG between July 2004 and May 2012, were reviewed in this study. RESULTS: Of the one hundred and nine men and 511 women examined, the mean +/- SD (standard deviation) ages were 48 +/- 14 in men (range: 19-79) and 51 +/- 16 in women (range: 18-84 years). The annual mean number of operation was 80 +/- 14 (range: 68-86). The mean operation time lasted 64 +/- 12 minutes (range: 48-95). About 2.3 +/- 0.4 (range: 1-4) parathyroid glands were observed during thyroidectomy. Parathyroid auto transplantation was performed in seventy-eight patients (12.5%). Patient-stay in hospital was approximately 2.3 +/- 0.3 days (range: 1-5). TT was performed in all patients as the primary operation. Pathologic findings revealed BMNG in four hundred and seventy (75.8%) cases, papillary carcinoma in 66 (10.3%), thyroiditis in 59 (9.5%), follicular carcinoma in 10 (1.6%), follicular adenoma in 5 (0.8%), and thyroid lymphoma in 3 cases (0.5%). Postoperatively, bilateral recurrent laryngeal nerve (RLN) injury was seen in one case (0.3%) and unilateral RLN injury in 5 (0.8%) cases. Three months later, only three cases (0.5%) were permanent. The histological diagnosis in all patients with permanent RLN injury was thyroiditis. Transient hypoparathyroidism was found in forty-eight cases (7.8%), three of which (0.5%) were permanent. Four cases were re-operated due to re-bleeding (0.6%). Seroma developed in three cases (0.5%) and wound infection in two (0.3%). CONCLUSION: TT can be performed safely by an experienced surgeon with a minimal risk in a high volume hospital. PMID- 26158251 TI - Significance of TNM staging, Demographic and Histologic Features in Predicting the Prognosis of Renal Cell Carcinoma. AB - BACKGROUND: The aim of this study was to evaluate the prognostic significance of clinical, demographic and detailed histopathological parameters in renal cell carcinoma (RCC). METHODS: A total of 102 patients who underwent partial or radical nephrectomy for a renal mass between 2008 and 2013 were evaluated retrospectively. Fuhrman grade, TNM stage, macroscopic satellite tumor nodule formation, histopathological subtype, renal vein invasion (RVI), necrosis, microvessel invasion (MVI), sarcomatoid differentiation and overall survival (OS) were evaluated to determine prognostic factors. RESULTS: The 102 patients consisted of 73 with clear cell tumor, 15 with papillary tumor, 12 with chromophobe tumor and 2 collecting duct RCC cases. A statistically negative relationship was observed between increasing age and OS when the patients were grouped as above and under 40 years of age. There was no statistical relationship between OS and histopathological subtype, adrenal gland invasion, and lymph node metastasis. The risk of death was 10-fold increased in patients with stage 4 tumor compared to patients with stage 1 tumor. Statistically significant macroscopical parameters for OS were satellite tumor nodule presence, Fuhrman grade, tumor size, renal sinus and perinephric fat invasion, distant metastasis, and RVI. The risk of death was 13-fold higher in cases with sarcomatoid differentiation. There was a strong correlation between the presence of a satellite tumor nodule, necrosis, sarcomatoid differentiation and the tumor stage. A statistically negative correlation was observed between OS and the MVI, sarcomatoid differentiation, and necrosis. CONCLUSION: We found the Fuhrman grade, tumor size, renal sinus and perinephric fat invasion, distant metastasis, RVI, MVI, sarcomatoid differentiation, necrosis and satellite tumor nodule to be all statistically significant parameters for OS. The addition of other variables to the TNM stage and grade may improve the prediction of outcomes for RCC patients. PMID- 26158252 TI - The Impact of Blunt Thoracic Aortic Injury on Patients Aged 80 Years or Older. AB - BACKGROUND: Blunt thoracic aortic injury (BTAI) is rare and associated with significant morbidity and mortality in trauma patients. As the population ages and life expectancy increases, the frequency of this injury will increase in the elderly and thus it behoves us to understand treatment and outcome in this patient population. METHODS: We analysed prospectively collected data of 10 patients > 80 years old with BTAI (Group A) treated among 26,000 trauma patients over a 20-year period in a Level 1 trauma center to investigate BTAI morbidity and mortality. Age, gender, and injurity severity score (ISS) matching was performed to create a case-control study of elderly trauma patients with (Group A) and without BTAI (Group B). RESULTS: Ten elderly trauma patients were found to have BTAI. Five (50%) were males and 5 (50%) were female. The cohort mean age was 86 years (range: 80 to 95). All but one patient (fall injury) were involved in motor vehicle accidents. The mean ISS in group A was 29 +/- 12. In group A, 2 (20%) patients (ISS = 36 and 33) succumbed in the emergency department. Six (60%) patients were treated non-operatively and the remaining 2 (20%) patients (88 and 84 years) underwent open aortic repair with patch angioplasty and Dacron interposition grafting. No postoperative paraplegia or stroke related to surgery occurred. Two patients in Group A survived hospitalization and were eventually discharged. Patients in Group B had lower overall LOS, ICU LOS and 30-day mortality rates despite similar ISS. CONCLUSION: Patients aged 80 or older who have experienced BTAI tend to have worse outcomes than those without BTAI regardless of similar ISS. Therefore, because of the low incident of this injury in general and particularly in the elderly, only pooled data from multiple institutions will be able to shed light on the complex issues surrounding treatment decisions in a group of patients with an a priori limited life expectancy. PMID- 26158253 TI - Contrast Enhanced Ultrasound (CEU) Using Microbubbles for Sentinel Lymph Node Biopsy in Breast Cancer: a Systematic Review. AB - BACKGROUND: The concept of sentinel lymph node (SLN) is not new to medical practice especially in breast cancer patients. CEU microbubble technique is an innovative technique which is applied with the same purpose. It utilizes ultrasound contrast agents based on the use of dispersion with sulfur hexafluoride gas. The aim of this review is to examine the clinical evidence on the role of intradermally injected microbubbles as a technique of preoperative identification of SLNs in patients with breast cancer. METHODS: A systematic search was performed in PubMed (5 October 2014), Scopus (5 October 2014) and Cochrane libraries (5 October 2014). RESULTS: Five prospective studies were included in the study. The total number of patients included was 727. The age of the included patients ranged from 19 to 93 years old. The median diameter of tumor ranged from 2 to 120 mm. Regarding the histological type, ductal carcinoma in situ was present in 31 patients, invasive ductal carcinoma in 438, invasive lobular carcinoma in 71 and not defined invasive breast tumors in 52 patients. The SLN identification rate ranged from 9.3% to 55.2% and the sensitivity from 61% to 89% while the false negative rate from 6.6% to 39% and the presence of micro/macrometastases from 1.9% to 64.3%. CONCLUSIONS: CEU microbubble technique is an alternative technique of SLN detection in breast cancer patients. Further studies are necessary to standardize the method and clarify its specificity and sensitivity. Moreover, randomized control trials are suggested in order to compare this technique with the current techniques used for SLN detection. PMID- 26158254 TI - Preclose Percutaneous EndurantTM Endografting with the ProglideTM Device: a Safe and Feasible Combination. AB - BACKGROUND: Endovascular repair of abdominal aortic aneurysms has been revolutionized over the last two decades. Opening the doors for a percutaneous approach by avoiding surgical exposure of the vascular access site. The goal of this report is to analyze the feasibility and efficacy of using Perclose ProglideTM through a preclose technique in a percutaneous approach to EndurantTM endografting for Asymptomatisch infrarenal aortic aneurysms in an elective setting. METHODS: Between April 2011 and April 2014, 45 consecutive patients underwent percutaneous endovascular aortic aneurysm repair (PEVAR) for an asymptomatic infrarenal aortic aneurysm. Closure of percutaneous access sites was ensured with Perclose Proglide in a "preclose" technique. Data were collected in a prospective maintained database with a follow-up period of one month. Patient demographics, aneurysmal characteristics, procedural details and complications were recorded. RESULTS: A total of 170 Proglide devices were used to close 85 access sites. Adequate hemostasis was obtained in 96.5 percent (82 of 85 access sites). Conversion to a femoral cutdown was necessary in 2.4% (2 of 85 access sites). The mean hospitalization was 2.6 days and 86.7 percent of patients were discharged within 2 days. The incidence of post-procedural access-related complications was 2.2%. CONCLUSIONS: PEVAR using the Perclose Proglide in preclosing 14Fr to 20Fr access sites for Endurant endografting in the treatment of asymptomatic infrarenal aortic aneurysms is feasible and effective. Moreover, the percutaneous approach allows for procedures to be performed under local anesthesia, while providing a low risk for access-related complications and a relatively short hospitalization. PMID- 26158255 TI - A Rare Case of Ileocolic Obstruction Due to Lithophagia Associated with Cervical Oesophageal Perforation. AB - Lithophagia is a rare syndrome characterized by a repetitive ingestion of stones and pebbles. We herein report a case of a 61-year old mentally retarded man, with a past surgical history of multiple laparotomies for stone ingestion, presenting with cervical oesophagus perforation due to a large butterfly screw and massive impaction of 89 stones and other foreign bodies in the caecum, with consequent mechanical bowel obstruction. PMID- 26158256 TI - Visceral Pseudoaneurysm Embolisation Using 'Ping-Pong' Technique: Importance of Dual Arterial Catheterisation to Prevent Rupture. AB - Supracolic peri-pancreatic visceral pseudoaneurysms combine the challenges of difficult location for open surgical repair with unpredictable risk of fatal exsanguination. Endovascular embolisation is a well-established method of safely decompressing these lesions using a variety of thrombogenic agents. A single catheter technique is commonly employed to achieve this outcome. However, there is also a risk of iatrogenic rupture during these procedures as a result of occlusion of one vessel allowing pressure to rise through any other vessel(s). Thus a thorough understanding of the flow dynamics prior to and during occlusion is essential for safe decompression. We report the adaptation of dual arterial catheter technique in treating these lesions in an 80-year old man with a large, leaking peripancreatic visceral pseudo-aneurysm. Our technique of alternating between intervention and observation of effect allows greater control of the potentially unpredictable haemodynamic situation. PMID- 26158257 TI - Severe Acute Postoperative Gastric Dilatation. PMID- 26158258 TI - Compensatory Lung Growth after Pneumonectomy: Case Report. AB - Lung expansion after pneumonectomy is well documented in animal models like dogs or mice. We present a lung expansion case after left pneumonectomy for an advanced carcinoid tumor in a 16-year-old patient with hemoptysis and acute dyspnea. This tumor was localized in the left upper lobe (LUL) invading the left main bronchus. During the follow-up we noticed a real growth of the remaining lung. PMID- 26158259 TI - Modified Sugiura Operation for Idiopathic Portal Hypertension with Bleeding Oesophageal Varices. A Case Report. AB - A case of a 36 years old man presenting massive upper GI bleeding due to oesophageal varices developed in the context of an idiopathic portal cavernoma and extensive porto-splenic thrombosis is discussed. He underwent a successful modified Sugiura operation (oesophago-gastric devascularisation and splenectomy [OGDS]) completed with interventional endoscopic treatment of residual oesophageal varices. The benefit of the modified Sugiura procedure proposed for the treatment of upper GI variceal bleeding developed in the context of splanchnic venous thrombosis is discussed. The procedure is a valid therapy in the treatment of symptomatic extra-hepatic hypertension when other options are inapplicable. PMID- 26158260 TI - The Cancer Diagnosis, Surgery and Cause of Death of Ivan Turgenev (1818-1883). PMID- 26158261 TI - The Development of Blood Transfusion: the Role of Albert Hustin and the Influence of World War I. PMID- 26158262 TI - Management of a Benign Phyllodes Tumor in a 13-Year-Old Girl with Trans-position of the Nipple Areola Complex and Breast Reconstruction. AB - Phyllodes tumor is a rare primary tumor of the breast. In children and adolescents, it is even rarer with only 20 cases, treatment of which vary in the literature. Herein we report the case of a 13-year-old female patient with a giant benign phyllodes tumor eroding the bottom of the breast skin and causing nipple retraction. We performed breast conservative surgery by mobilizing the areola, using skin flaps and inserting an implant. Breast malignancy, including phyllodes tumor (PT), is very rare in adolescents. PT, previously called cystosarcoma phylloides, consists of leaf-like fronds, from which the tumor gets its name (1, 2). Although PT is most often seen in the fourth decade of life, almost 20 cases have been reported in the adolescent period, most of which are benign. The histologic types are benign, borderline, and malignant, depending on the mitotic rate of the tumor (3, 4). PMID- 26158263 TI - Suggestions for health information technology trials for respiratory disorders in low- and middle-income country settings: what can we learn from trials in high income country settings? AB - Health Information Technology (HIT) is sometimes seen as a silver bullet for human resource, medical and economic challenges facing health systems. The evidence supporting widespread use of HIT is, however, still patchy and inconsistent. In this Perspective piece, we seek to interpret and draw key lessons from a selection of illustrative trials in developed countries with robust health-care settings in respiratory medicine that failed to demonstrate effectiveness, and offer suggestions to maximise the chances of success in subsequent HIT deployments. Particularly low- and middle-income countries, with relatively weak health infrastructures and limited health care, propose considerable room for improvement. Early experiences of studying HIT thus far in high-income country settings suggest that this process should preferably begin with trials of low-cost, well-established technologies in patient groups with a moderate burden of disease while carefully evaluating patient safety. PMID- 26158264 TI - gamma-PGA Hydrolases of Phage Origin in Bacillus subtilis and Other Microbial Genomes. AB - Poly-gamma-glutamate (gamma-PGA) is an industrially interesting polymer secreted mainly by members of the class Bacilli which forms a shield able to protect bacteria from phagocytosis and phages. Few enzymes are known to degrade gamma PGA; among them is a phage-encoded gamma-PGA hydrolase, PghP. The supposed role of PghP in phages is to ensure access to the surface of bacterial cells by dismantling the gamma-PGA barrier. We identified four unannotated B. subtilis genes through similarity of their encoded products to PghP; in fact these genes reside in prophage elements of B. subtilis genome. The recombinant products of two of them demonstrate efficient polymer degradation, confirming that sequence similarity reflects functional homology. Genes encoding similar gamma-PGA hydrolases were identified in phages specific for the order Bacillales and in numerous microbial genomes, not only belonging to that order. The distribution of the gamma-PGA biosynthesis operon was also investigated with a bioinformatics approach; it was found that the list of organisms endowed with gamma-PGA biosynthetic functions is larger than expected and includes several pathogenic species. Moreover in non-Bacillales bacteria the predicted gamma-PGA hydrolase genes are preferentially found in species that do not have the genetic asset for polymer production. Our findings suggest that gamma-PGA hydrolase genes might have spread across microbial genomes via horizontal exchanges rather than via phage infection. We hypothesize that, in natural habitats rich in gamma-PGA supplied by producer organisms, the availability of hydrolases that release glutamate oligomers from gamma-PGA might be a beneficial trait under positive selection. PMID- 26158265 TI - Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial. AB - Epidemiological studies suggest a dose-response relationship exists between physical activity and cognitive outcomes. However, no direct data from randomized trials exists to support these indirect observations. The purpose of this study was to explore the possible relationship of aerobic exercise dose on cognition. Underactive or sedentary participants without cognitive impairment were randomized to one of four groups: no-change control, 75, 150, and 225 minutes per week of moderate-intensity semi-supervised aerobic exercise for 26-weeks in a community setting. Cognitive outcomes were latent residual scores derived from a battery of 16 cognitive tests: Verbal Memory, Visuospatial Processing, Simple Attention, Set Maintenance and Shifting, and Reasoning. Other outcome measures were cardiorespiratory fitness (peak oxygen consumption) and measures of function functional health. In intent-to-treat (ITT) analyses (n = 101), cardiorespiratory fitness increased and perceived disability decreased in a dose-dependent manner across the 4 groups. No other exercise-related effects were observed in ITT analyses. Analyses restricted to individuals who exercised per-protocol (n = 77) demonstrated that Simple Attention improved equivalently across all exercise groups compared to controls and a dose-response relationship was present for Visuospatial Processing. A clear dose-response relationship exists between exercise and cardiorespiratory fitness. Cognitive benefits were apparent at low doses with possible increased benefits in visuospatial function at higher doses but only in those who adhered to the exercise protocol. An individual's cardiorespiratory fitness response was a better predictor of cognitive gains than exercise dose (i.e., duration) and thus maximizing an individual's cardiorespiratory fitness may be an important therapeutic target for achieving cognitive benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT01129115. PMID- 26158266 TI - Inhibition of Aerobic Glycolysis Represses Akt/mTOR/HIF-1alpha Axis and Restores Tamoxifen Sensitivity in Antiestrogen-Resistant Breast Cancer Cells. AB - Tamoxifen resistance is often observed in the majority of estrogen receptor positive breast cancers and it remains as a serious clinical problem in breast cancer management. Increased aerobic glycolysis has been proposed as one of the mechanisms for acquired resistance to chemotherapeutic agents in breast cancer cells such as adriamycin. Herein, we report that the glycolysis rates in LCC2 and LCC9--tamoxifen-resistant human breast cancer cell lines derived from MCF7--are higher than those in MCF7S, which is the parent MCF7 subline. Inhibition of key glycolytic enzyme such as hexokinase-2 resulted in cell growth retardation at higher degree in LCC2 and LCC9 than that in MCF7S. This implies that increased aerobic glycolysis even under O2-rich conditions, a phenomenon known as the Warburg effect, is closely associated with tamoxifen resistance. We found that HIF-1alpha is activated via an Akt/mTOR signaling pathway in LCC2 and LCC9 cells without hypoxic condition. Importantly, specific inhibition of hexokinase-2 suppressed the activity of Akt/mTOR/HIF-1alpha axis in LCC2 and LCC9 cells. In addition, the phosphorylated AMPK which is a negative regulator of mTOR was decreased in LCC2 and LCC9 cells compared to MCF7S. Interestingly, either the inhibition of mTOR activity or increase in AMPK activity induced a reduction in lactate accumulation and cell survival in the LCC2 and LCC9 cells. Taken together, our data provide evidence that development of tamoxifen resistance may be driven by HIF-1alpha hyperactivation via modulation of Akt/mTOR and/or AMPK signaling pathways. Therefore, we suggest that the HIF-1alpha hyperactivation is a critical marker of increased aerobic glycolysis in accordance with tamoxifen resistance and thus restoration of aerobic glycolysis may be novel therapeutic target for treatment of tamoxifen-resistant breast cancer. PMID- 26158268 TI - Predictors of Childhood Anxiety: A Population-Based Cohort Study. AB - BACKGROUND: Few studies have explored predictors of early childhood anxiety. OBJECTIVE: To determine the prenatal, postnatal, and early life predictors of childhood anxiety by age 5. METHODS: Population-based, provincial administrative data (N = 19,316) from Manitoba, Canada were used to determine the association between demographic, obstetrical, psychosocial, medical, behavioral, and infant factors on childhood anxiety. RESULTS: Risk factors for childhood anxiety by age 5 included maternal psychological distress from birth to 12 months and 13 months to 5 years post-delivery and an infant 5-minute Apgar score of <=7. Factors associated with decreased risk included maternal age < 20 years, multiparity, and preterm birth. CONCLUSION: Identifying predictors of childhood anxiety is a key step to early detection and prevention. Maternal psychological distress is an early, modifiable risk factor. Future research should aim to disentangle early life influences on childhood anxiety occurring in the prenatal, postnatal, and early childhood periods. PMID- 26158267 TI - Abnormal Accumulation of Collagen Type I Due to the Loss of Discoidin Domain Receptor 2 (Ddr2) Promotes Testicular Interstitial Dysfunction. AB - BACKGROUND: Loss of functional allele for discoidin domain receptor 2 (Ddr2) results in impaired Leydig cell response to luteinizing hormone (LH), low testosterone production and arrested spermatogenesis in older male Ddr2slie/slie mice. However, the underlying mechanism responsible for this phenotype remains unknown. Herein, we reported for the first time that the deregulated expression of Ddr2 cognate ligand, namely collagen type I (COL1), may account for the disruption of the testicular steroidogenesis in Ddr2slie/slie mutant testes. METHODOLOGY/PRINCIPAL FINDINGS: Expression of Ddr2 increased gradually along postnatal development, whereas COL1 expression became negligible from adulthood onwards. In Ddr2slie/slie mutant testis, however, in contrast to the undetectable staining of Ddr2, COL1 expression was constantly detected, with the highest values detected during adulthood. In the experimental vasectomy model, Ddr2slie/slie mutant mice exhibited an early androgen deficiency than wild-type mice, along with the accumulation of fibrotic tissue in the interstitium. Functionally, ablation of endogenous Ddr2 resulted in a significant decrease of testosterone (T) level in TM3 cells in the presence of higher concentration of COL1 treatment. Conversely, overexpression of Ddr2 could help TM3 cells to maintain a normal testicular steroidogenesis even in the presence of high concentration of COL1. Additionally, attenuated expression of Ddr2 correlates to the deregulated level of serum T levels in human pathological testes. CONCLUSIONS: Abnormal accumulation of interstitial COL1 may be responsible for the steroidogenic dysfunction in Ddr2slie/slie mutant testes. PMID- 26158269 TI - IDH-Mutation Is a Weak Predictor of Long-Term Survival in Glioblastoma Patients. AB - BACKGROUND: A very small proportion of patients diagnosed with glioblastoma (GBM) survive more than 3 years. Isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations define a small subgroup of GBM patients with favourable prognosis. However, it remains controversial whether long-term survivors (LTS) are found among those IDH1/2 mutated patients. METHODS: We retrospectively analyzed 207 GBM patients followed at Lariboisiere Hospital (Paris) between 2005 and 2010. Clinical parameters were obtained from medical records. Mutations of IDH1/2 were analyzed in these patients, by immunohistochemistry for the R132H mutation of IDH1 and by high-resolution melting-curve analysis, followed by Sanger sequencing for IDH1 and IDH2 exon 4 mutations. Mutation rates in LTS and non-LTS groups were compared by Chi square Pearson test. RESULTS: Seventeen patients with survival >3 years were identified (8.2% of the total series). The median overall survival in long term survivors was 4.6 years. Subgroup analysis found that the median age at diagnosis was significantly higher for non long-term survivors (non-LTS) compared to LTS (60 versus 51 years, p <0.03). The difference in the rate of IDH mutation between non-LTS and LTS was statistically not significant (1.16% versus 5.9%, p = 0.144). Among LTS, 10 out of 16 tumors presented a methylation of MGMT promoter. CONCLUSIONS: This study confirms that long-term survival in GBM patients is if at all only weakly correlated to IDH-mutation. PMID- 26158270 TI - Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent. AB - An increasing number of broadly neutralizing antibodies (bnAbs) are considered leads for HIV-1 vaccine development and novel therapeutics. Here, we systematically explored the capacity of bnAbs to neutralize HIV-1 prior to and post-CD4 engagement and to block HIV-1 cell-cell transmission. Cell-cell spread is known to promote a highly efficient infection with HIV-1 which can inflict dramatic losses in neutralization potency compared to free virus infection. Selection of bnAbs that are capable of suppressing HIV irrespective of the transmission mode therefore needs to be considered to ascertain their in vivo activity in therapeutic use and vaccines. Employing assay systems that allow for unambiguous discrimination between free virus and cell-cell transmission to T cells, we probed a panel of 16 bnAbs for their activity against 11 viruses from subtypes A, B and C during both transmission modes. Over a wide range of bnAb virus combinations tested, inhibitory activity against HIV-1 cell-cell transmission was strongly decreased compared to free virus transmission. Activity loss varied considerably between virus strains and was inversely associated with neutralization of free virus spread for V1V2- and V3-directed bnAbs. In rare bnAb virus combinations, inhibition for both transmission modes was comparable but no bnAb potently blocked cell-cell transmission across all probed virus strains. Mathematical analysis indicated an increased probability of bnAb resistance mutations to arise in cell-cell rather than free virus spread, further highlighting the need to block this pathway. Importantly, the capacity to efficiently neutralize prior to CD4 engagement correlated with the inhibition efficacy against free virus but not cell-cell transmitted virus. Pre-CD4 attachment activity proved strongest amongst CD4bs bnAbs and varied substantially for V3 and V1V2 loop bnAbs in a strain-dependent manner. In summary, bnAb activity against divergent viruses varied depending on the transmission mode and differed depending on the window of action during the entry process, underscoring that powerful combinations of bnAbs are needed for in vivo application. PMID- 26158271 TI - Biofilm Formation As a Response to Ecological Competition. AB - Bacteria form dense surface-associated communities known as biofilms that are central to their persistence and how they affect us. Biofilm formation is commonly viewed as a cooperative enterprise, where strains and species work together for a common goal. Here we explore an alternative model: biofilm formation is a response to ecological competition. We co-cultured a diverse collection of natural isolates of the opportunistic pathogen Pseudomonas aeruginosa and studied the effect on biofilm formation. We show that strain mixing reliably increases biofilm formation compared to unmixed conditions. Importantly, strain mixing leads to strong competition: one strain dominates and largely excludes the other from the biofilm. Furthermore, we show that pyocins, narrow-spectrum antibiotics made by other P. aeruginosa strains, can stimulate biofilm formation by increasing the attachment of cells. Side-by-side comparisons using microfluidic assays suggest that the increase in biofilm occurs due to a general response to cellular damage: a comparable biofilm response occurs for pyocins that disrupt membranes as for commercial antibiotics that damage DNA, inhibit protein synthesis or transcription. Our data show that bacteria increase biofilm formation in response to ecological competition that is detected by antibiotic stress. This is inconsistent with the idea that sub-lethal concentrations of antibiotics are cooperative signals that coordinate microbial communities, as is often concluded. Instead, our work is consistent with competition sensing where low-levels of antibiotics are used to detect and respond to the competing genotypes that produce them. PMID- 26158272 TI - SNP Analysis Infers that Recombination Is Involved in the Evolution of Amitraz Resistance in Rhipicephalus microplus. AB - Rhipicephalus microplus, better known as the Asiatic cattle tick, is a largely invasive ectoparasite of great economic importance due to the negative effect it has on agricultural livestock on a global scale, particularly cattle. Tick-borne diseases (babesiosis and anaplasmosis) transmitted by R. microplus are alarming as they decrease the quality of livestock health and production. In sub-Saharan Africa, cattle represent a major source of meat and milk, but this region of the world is severely affected by the Rhipicephalus microplus tick. The principal method for tick control is the use of chemical acaricides, notably amitraz, which was implemented in the 1990's after resistance to other acaricides surfaced. However, the efficiency of chemical control is hindered by an increase in the frequency of mutant resistance alleles to amitraz in tick populations. Presently, the only way to assess amitraz resistance is by means of larval packet tests, but this technique is time-consuming and not particularly cost effective. The main aims of this study were three-fold. First, we attempted to correlate two known SNPs in the octopamine/tyramine (OCT/Tyr) receptor with amitraz resistance in South African field samples of R. microplus. Second, we calculated gametic disequilibrium for these SNPs to determine whether they are randomly associated. Lastly, we conducted a study to assess the evolutionary effects of recombination within the OCT/Tyr receptor. Our results confirmed that the two SNPs are associated with amitraz resistance in the South African tick strain, and that they are in gametic disequilibrium. Additionally, recombination was detected in the OCT/Tyr receptor generating two recombinant haplotypes. These results are of concern to farmers in sub-Saharan Africa, and the emergence of amitraz resistance should be closely monitored in future. Therefore, we present a quick and affordable RFLP based diagnostic technique to assess amitraz resistance in field samples of R. microplus. PMID- 26158273 TI - Neorickettsia sennetsu as a Neglected Cause of Fever in South-East Asia. AB - Neorickettsia sennetsu infection is rarely recognized, with less than 100 globally reported patients over the last 50 years. The disease is thought to be contracted by eating raw fish, a staple of many South-East Asian cuisines. In 2009, the first patient with sennetsu was identified in the Lao PDR (Laos), raising the question as to how common this organism and related species are in patients presenting with fever. We investigated the frequency of N. sennetsu infection at hospitals in diverse areas of Laos. Consenting febrile hospital inpatients from central (Vientiane: n = 1,013), northern (Luang Namtha: n = 453) and southern (Salavan: n = 171) Laos were screened by PCR for N. sennetsu, if no previous positive direct diagnostic test was available. A PCR-restriction fragment length polymorphism assay was developed to differentiate between N. sennetsu, Ehrlichia chaffeensis and Anaplasma phagocytophilum. To allow more detailed studies of N. sennetsu, culture was successfully established using a reference strain (ATCC VR-367), identifying a canine-macrophage cell line (DH82) to be most suitable to visually identify infection. After screening, N. sennetsu was identified and sequence confirmed in four (4/1,637; 0.2%) Lao patients. Despite the previously identified high seroprevalence of N. sennetsu antibodies in the Lao population (~17%), acute N. sennetsu infection with sufficient clinical signs to prompt hospitalization appears to be rare. The reservoir, zoonotic cycle and pathogenicity of N. sennetsu remain unclear and require further investigations. PMID- 26158274 TI - Evaluating Spatial Interaction Models for Regional Mobility in Sub-Saharan Africa. AB - Simple spatial interaction models of human mobility based on physical laws have been used extensively in the social, biological, and physical sciences, and in the study of the human dynamics underlying the spread of disease. Recent analyses of commuting patterns and travel behavior in high-income countries have led to the suggestion that these models are highly generalizable, and as a result, gravity and radiation models have become standard tools for describing population mobility dynamics for infectious disease epidemiology. Communities in Sub-Saharan Africa may not conform to these models, however; physical accessibility, availability of transport, and cost of travel between locations may be variable and severely constrained compared to high-income settings, informal labor movements rather than regular commuting patterns are often the norm, and the rise of mega-cities across the continent has important implications for travel between rural and urban areas. Here, we first review how infectious disease frameworks incorporate human mobility on different spatial scales and use anonymous mobile phone data from nearly 15 million individuals to analyze the spatiotemporal dynamics of the Kenyan population. We find that gravity and radiation models fail in systematic ways to capture human mobility measured by mobile phones; both severely overestimate the spatial spread of travel and perform poorly in rural areas, but each exhibits different characteristic patterns of failure with respect to routes and volumes of travel. Thus, infectious disease frameworks that rely on spatial interaction models are likely to misrepresent population dynamics important for the spread of disease in many African populations. PMID- 26158275 TI - Analysis of the safety and efficacy of diabetic ketoacidosis management in a Community General Hospital, 2001-2010: a descriptive study. AB - BACKGROUND: The recommended place for treatment of diabetic ketoacidosis in children is a paediatric High Dependency Unit. This facility is not available in all areas where children with type 1 diabetes mellitus are cared for. AIMS: This study investigates the safety and efficacy of diabetic ketoacidosis management in a community general hospital without a paediatric high dependency unit. METHODS: Data from children with diabetic ketoacidosis were collected from all diabetes related admissions in Dr Gray's Hospital, Elgin from 2001 to 2010. Observations were compared with safety indicators (pH, bicarbonate, glucose, electrolytes and cerebral oedema) and were reviewed for the recovery to normal values (pH, bicarbonate), without abnormal fluctuation (electrolytes, glucose) and without neurological complications (cerebral oedema). RESULTS: The 114 patients generated 251 diabetes-related admissions, 118 for diabetic ketoacidosis treatment of whom 99 patients were treated with intravenous fluids and insulin. The mean time to recover to a pH of at least 7.30 was 655 minutes (120-1410 min). There were 79 (4.37% of 1808) glucose readings dropping more than 5.0 mmol/l per hour. There were six hypoglycaemic events (2.3-2.9 mmol/l) and in one case potassium dropped to 2.2 mmol/l. There was no case which developed into cerebral oedema. CONCLUSION: Treatment of diabetic ketoacidosis in a community general hospital managed with a protocol for fluids, insulin and strict monitoring has shown to be effective in achieving recovery and to safely avoid complications. PMID- 26158276 TI - What happens when GPs engage in commissioning? Two decades of experience in the English NHS. AB - OBJECTIVE: To review the evidence on commissioning schemes involving clinicians in the United Kingdom National Health Service, between 1991 and 2010; report on the extent and impact of clinical engagement; and distil lessons for the development of such schemes both in the UK and elsewhere. METHODS: A review of published evidence. Five hundred and fourteen abstracts were obtained from structured searches and screened. Full-text papers were retrieved for UK empirical studies exploring the relationship between commissioners and providers with clinician involvement. Two hundred and eighteen published materials were reviewed. RESULTS: The extent of clinical engagement varied between the various schemes. Schemes allowing clinicians to act autonomously were more likely to generate significant engagement, with 'virtuous cycles' (experience of being able to make changes feeding back to encourage greater engagement) and 'vicious cycles' (failure to influence services generating disengagement) observed. Engagement of the wider general practitioner (GP) membership was an important determinant of success. Most impact was seen in GP prescribing and the establishment of services in general practices. There was little evidence of GPs engaging more widely with public health issues. CONCLUSION: Evidence for a significant impact of clinical engagement on commissioning outcomes is limited. Initial changes are likely to be small scale and to focus on services in primary care. Engagement of GP members of primary care commissioning organizations is an important determinant of progress, but generates significant transaction costs. PMID- 26158278 TI - A Cogent Case for a New Child Custody Standard. PMID- 26158277 TI - A Critical Assessment of Child Custody Evaluations: Limited Science and a Flawed System. AB - -Most parents who live apart negotiate custody arrangements on their own or with the help of lawyers, mediators, or other professionals. However, psychologists and other mental health professionals increasingly have become involved in evaluating children and families in custody disputes, because of the large number of separated, divorced, and never-married parents and the substantial conflict that often accompanies the breakup of a family. Theoretically, the law guides and controls child custody evaluations, but the prevailing custody standard (the "best interests of the child" test) is a vague rule that directs judges to make decisions unique to individual cases according to what will be in children's future (and undefined) best interests. Furthermore, state statutes typically offer only vague guidelines as to how judges (and evaluators) are to assess parents and the merits of their cases, and how they should ultimately decide what custody arrangements will be in a child's best interests. In this vacuum, custody evaluators typically administer to parents and children an array of tests and assess them through less formal means including interviews and observation. Sadly, we find that (a) tests specifically developed to assess questions relevant to custody are completely inadequate on scientific grounds; (b) the claims of some anointed experts about their favorite constructs (e.g., "parent alienation syndrome") are equally hollow when subjected to scientific scrutiny; (c) evaluators should question the use even of well-established psychological measures (e.g., measures of intelligence, personality, psychopathology, and academic achievement) because of their often limited relevance to the questions before the court; and (d) little empirical data exist regarding other important and controversial issues (e.g., whether evaluators should solicit children's wishes about custody; whether infants and toddlers are harmed or helped by overnight visits), suggesting a need for further scientific investigation. We see the system for resolving custody disputes as deeply flawed, for reasons that go beyond the problem of limited science. The coupling of the vague "best interests of the child" test with the American adversary system of justice puts judges in the position of trying to perform an impossible task, and it exacerbates parental conflict and problems in parenting and coparenting, which psychological science clearly shows to be key factors predicting children's psychological difficulties in response to their parents' separation and divorce. Our analysis of the flawed system, together with our desire to sharply limit custody disputes and custody evaluations, leads us to propose three reforms. First, we urge continued efforts to encourage parents to reach custody agreements on their own-in divorce mediation, through collaborative law, in good-faith attorney negotiations, in therapy, and in other forums. Some such efforts have been demonstrated to improve parent-parent and parent-child relationships long after divorce, and they embrace the philosophical position that, in the absence of abuse or neglect, parents themselves should determine their children's best interests after separation, just as they do in marriage. Second, we urge state legislatures to move toward adopting more clear and determinative custody rules, a step that would greatly clarify the terms of the marriage contract, limit the need for custody evaluations, and sharply narrow the scope of the evaluation process. We find particular merit in the proposed "approximation rule" (recently embraced by the American Law Institute), in which postdivorce parenting arrangements would approximate parenting involvement in marriage. Third and finally, we recommend that custody evaluators follow the law and only offer opinions for which there is an adequate scientific basis. Related to this, we urge professional bodies to enact more specific standards of practice on this and related issues. PMID- 26158279 TI - Melatonin Interaction Resulting in Severe Sedation. AB - PURPOSE: Natural health products (NHPs), including melatonin, are widely used products. Despite the widespread assumption that all NHPs are safe, they contain pharmacologically active substances and can therefore have adverse effects and/or interact with pharmaceuticals. OBJECTIVE: To investigate the mechanism underlying NHP interactions identified through the Pharmacy SONAR active surveillance study. METHODS: Active surveillance was undertaken in community pharmacies to identify adverse events in patients who had recently taken NHPs together with conventional pharmaceuticals. For suspected NHP-pharmaceutical interactions, the possible mechanism of action was explored by in vitro analysis of samples of different products to identify cytochrome P450 enzyme (CYP) inhibition potential. RESULTS: Active surveillance identified a 19-year-old male taking citalopram, nortriptyline and oxycodone concomitantly and who experienced severe sedation when melatonin was added to this regimen. In vitro analysis involving several melatonin products showed product-dependent inhibition of CYP1A2, CYP2C19 and CYP3A7. CONCLUSION: The adverse event was likely due to a primary pharmacokinetic interaction between melatonin and citalopram; although mechanistically, interactions affecting cytochrome P450-mediated metabolism may have occurred with all of these health products. A pharmacodynamic interaction may also be possible, but beyond the capacity of this study to establish. PMID- 26158280 TI - Phytoestrogens Modulate Breast Cancer Resistance Protein Expression and Function at the Blood-Cerebrospinal Fluid Barrier. AB - PURPOSE: Breast cancer resistance protein (BCRP/ABCG2) is a drug efflux transporter expressed at the blood cerebrospinal fluid barrier (BCSFB), and influences distribution of drugs into the central nervous systems (CNS). Current inhibitors have failed clinically due to neurotoxicity. Novel approaches are needed to identify new modulators to enhance CNS delivery. This study examines 18 compounds (mainly phytoestrogens) as modulators of the expression/function of BCRP in an in vitro rat choroid plexus BCSFB model. METHODS: Modulators were initially subject to cytotoxicity (MTT) assessment to determine optimal non-toxic concentrations. Reverse-transcriptase PCR and confocal microscopy were used to identify the presence of BCRP in Z310 cells. Thereafter modulation of the intracellular accumulation of the fluorescent BCRP probe substrate Hoechst 33342 (H33342), changes in protein expression of BCRP (western blotting) and the functional activity of BCRP (membrane insert model) were assessed under modulator exposure. RESULTS: A 24 hour cytotoxicity assay (0.001 uM-1000 uM) demonstrated the majority of modulators possessed a cellular viability IC50 > 148 uM. Intracellular accumulation of H33342 was significantly increased in the presence of the known BCRP inhibitor Ko143 and, following a 24 hour pre-incubation, all modulators demonstrated statistically significant increases in H33342 accumulation (P < 0.001), when compared to control and Ko143. After a 24 hour pre incubation with modulators alone, a 0.16-2.5 -fold change in BCRP expression was observed for test compounds. The functional consequences of this were confirmed in a permeable insert model of the BCSFB which demonstrated that 17-beta estradiol, naringin and silymarin (down-regulators) and baicalin (up-regulator) can modulate BCRP-mediated transport function at the BCSFB. CONCLUSION: We have successfully confirmed the gene and protein expression of BCRP in Z310 cells and demonstrated the potential for phytoestrogen modulators to influence the functionality of BCRP at the BCSFB and thereby potentially allowing manipulation of CNS drug disposition. PMID- 26158281 TI - Efficient Peroral Delivery of Insulin via Vitamin B12 Modified Trimethyl Chitosan Nanoparticles. AB - PURPOSE: We investigated the effect of vitamin B12 (VB12) modification on the insulin absorption from trimethyl chitosan(TMC) nanoparticles (NPs) under the influence of mucus. METHODS: TMC and TMC-VB12 were synthesized and insulin loaded TMC/TMC-VB12 nanoparticles were prepared and characterized. Modified and unmodified nanoparticles were studied with Caco-2/HT29-MTX cell model and ligated rat ileum loop. RESULTS: Compared with unmodified NPs, VB12 modified NPs showed significantly higher drug internalization in Caco-2/HT29-MTX cell model. The internalization mechanism via VB12 mediation included caveolae and clathrin mediated endocytosis pathway. Meanwhile, an increased transportation of drugs was observed for VB12 modified NPs, possibly due to the ligand-receptor interaction via an intrinsic factor-dependent fashion. Although the uptake and transport of VB12 modified NPs could be partially influenced by mucus, they still showed higher drug permeation through Caco-2/HT29-MTX co-cultured cells than unmodified NPs in the presence or absence of mucus. Moreover, in situ study in ligated rat ileum loop demonstrated that VB12 modified nanoparticles could reduce the residual insulin in intestinal lumen (0.59 times) and increase their absorption in epithelial tissue (4.8 times) compared with the unmodified ones. CONCLUSION: VB12 modified trimethyl chitosan nanoparticle is a promising carrier for peroral delivery of insulin. PMID- 26158282 TI - Intracellular and Plasma Trough Concentration and Pharmacogenetics of Telaprevir. AB - PURPOSE: Triple therapy for HCV-1 infection consists in boceprevir or telaprevir, ribavirin and PEG-interferon. Telaprevir is a P-glycoprotein substrate and it is metabolized by CYP3A4/5. No data have been published on intracellular penetration of telaprevir. We determined peripheral blood mononuclear cells (PBMCs) and trough plasma S and R telaprevir isomers concentrations; moreover, we evaluated the influence of some single nucleotide polymorphisms (SNPs) on these pharmacokinetic data after 1 month of triple therapy in humans. METHODS: Plasma and intracellular telaprevir concentrations were determined at the end of dosing interval (Ctrough) using ULPC-MS/MS validated methods; allelic discrimination was performed through real-time PCR. RESULTS: Median telaprevir Ctrough plasma concentrations were 2579 ng/mL and 2233 ng/mL for the pharmacologically more active S, and R, enantiomers, respectively, with median S/R plasma ratio of 1.11. In PBMC, the medians were 6863 ng/mL and 1096 ng/mL for S and R, respectively, with median S/R being 5.73. The PBMC:plasma ratio for S was 2.59 for R. Plasma ribavirin concentrations were directly correlated with plasma S-telaprevir concentrations. In linear regression analysis, only CYP24A1_rs2585428 SNP (p=0.003) and body mass index (p=0.038) were able to predict S-telaprevir PBMC concentrations. CONCLUSIONS: Our preliminary data could increase the understanding of mechanisms underlying telaprevir intracellular and plasma exposure, suggesting the implementation of pharmacogenetics in these drug kinetic studies. PMID- 26158283 TI - Subsequent Entry Biologics in Canada: Current State of the Science. AB - The Canadian Society for Pharmaceutical Sciences organized a workshop on the current state of sciences of subsequent entry biologics (SEBs, biosimilars) on December 10th 2014 in the Health Canada location in Ottawa, ON. The day-long workshop provided an opportunity to discuss recent regulatory developments and a wide range of scientific issues related to SEBs. Following a discussion on the differences between the Canadian guidance and those of other countries, a series of presentations were made that focused on the regulatory requirements with regard to the product quality, methodology, non-clinical and clinical data. In addition, issues of extrapolation from one indication to another, interchangeability and reimbursement were articulated. It was also highlighted that both the patients and caregivers need to be better informed regarding the safety and efficacy of articulated SEBs. PMID- 26158284 TI - A Simple Method to Extract Whole Apolipoproteins for the Preparation of Discoidal Recombined High Density Lipoproteins as Bionic Nanocarriers for Drug Delivery. AB - PURPOSE: To develop a simple method to extract the whole apolipoproteins (apo) including apoA-I in native high density lipoproteins (HDLs) and prepare discoidal Tanshinone IIA-loaded reconstituted HDL (TA-rHDLs) as a dual functional drug delivery system with plaque-site target and therapeutic promises in atherosclerotic lesions. METHODS: A method based on isoelectric precipitation coupled with organic solvent precipitation was developed to isolate the whole apolipoproteins (apos). TA-rHDLs were prepared by incubating the resultant apos with liposomes and the incubation conditions were optimized using fluorescence quenching experiment. TA-rHDLs were characterized in terms of size, zeta potential, morphology, interaction between lipid and apos, safety, and bionic function. RESULTS: The extraction results showed that the yield of the HDL apos was 82.4%, with 59% being apoA-I type, similar ratio of apoA-I in the native apos. TA-rHDL prepared were disc-like with an average diameter of 157.6 +/- 4.8 nm, zeta potential of -20.90 +/- 0.15 mV, and entrapment efficiency of (90.13 +/- 1.4) %. The interaction between the lipids and apos was electrostatic and hydrophobic force and was associated with amino acid sequence. Haemolysis and cytotoxicity assays showed good biocompatibility of TA-rHDL. Sterol efflux assay from macrophages mediated by TA-rHDLs and structure remodeling behavior from discs to spheres proved that TA-rHDL could resemble the biological activity of native nascent HDL irrespective of the size. CONCLUSIONS: The simple approach to isolate apos may provide a convenient and economical resource to support the development of rHDL as a potential targeting nanocarrier for lipophilic cardiovascular drugs. PMID- 26158285 TI - Effect of Desflurane versus Sevoflurane in Pediatric Anesthesia: A Meta-Analysis. AB - PURPOSE: To compare the effect of desflurane versus sevoflurane in pediatric anesthesia by conducting meta-analysis. METHODS: Studies were searched from PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar up to July 2014. Weighted mean difference (WMD) or risk ratio (RR) and 95% confidence intervals (CIs) were considered as effect sizes. Heterogeneity across studies was assessed by Cochran Q test and I2 statistic. The random effects model was performed in the meta-analysis when heterogeneity was observed, or the fixed effect model was used. Review Manager 5.1 software was applied for the meta-analysis. RESULTS: A total of 11 studies (13 comparisons) involving 1,273 objects were included in this meta-analysis. No heterogeneity was observed between studies for any comparison but for postoperative extubation time. The results showed significant differences between desflurane and sevoflurane groups for postoperative extubation time (WMD = -3.87, 95%CI = -6.14 to -1.60, P < 0.01), eye opening time (WMD = -1.11, 95%CI = -1.49 to -0.72, P < 0.01), awakening time (WMD = -4.27, 95%CI = -5.28 to -3.26, P < 0.01) and agitation (RR = 1.44, 95%CI = 1.05 to 1.96, P = 0.02). No significant differences (P > 0.05) were detected for discharge from the recovery room, oculocardiac reflex, nausea and vomiting and severe pain. CONCLUSIONS: Desflurane may have less adverse effects than sevoflurane when used in pediatric anesthesia with significantly shorter postoperative extubation time, eye opening time and awakening time as well as slighter agitation. PMID- 26158286 TI - Extraction and Analysis of Methadone in Exhaled Breath Condensate Using a Validated LC-UV Method. AB - PURPOSE: A combined microextraction and separation method is presented for the determination of methadone in exhaled breath condensate (EBC) which is a promising non-invasive biological component for monitoring drug concentrations. METHODS: In this work, dispersive liquid-liquid microextraction (DLLME) and ultrasonic liquid-liquid microextraction (ULLME) procedure coupled with a validated liquid chromatography method were used for analysis of methadone in EBC collected using an in-house cold trap setup. The method has been validated according to the FDA guidelines using EBC-spiked samples and tested on a number of EBC samples collected from patients. RESULTS: The best DLLME conditions involved the use of a disperser solvent of methanol (1 mL), extraction solvent of chloroform (200 mL), EBC sample pH of 10.0 and centrifugation at 6000 rpm for 5 minutes. The conditions for ULLME were 150 mL of chloroform and the samples were sonicated for 4 minutes. The method was validated over the concentration range of 0.5-10 mg/L-1 in EBC. Inter- and intra-day precision and accuracy were less than 5 % where the acceptable levels are less than 20%. Furthermore, the validated method was successfully applied for the determination of methadone in patients' EBC samples. CONCLUSIONS: The outcomes indicate that the developed LC-UV combined with DLLME and/or ULLME extraction methods can be employed for the extraction and separation of methadone in EBC samples. PMID- 26158287 TI - Strategies for Developing Oral Vaccines for Human Papillomavirus (HPV) Induced Cancer using Nanoparticle mediated Delivery System. AB - Human Papillomaviruses (HPV) are a diverse group of small non-enveloped DNA viruses. Some HPVs are classified as low-risk as they are very rarely associated with neoplasia or cancer in the general population, and cause lenient warts. Other HPVs are considered as high-risk types because they are responsible for several important human cancers, including cervical cancer, a large proportion of other anogenital cancers, and a growing number of head and neck cancers. Transmission of HPV occurs primarily by skin-to-skin contact. The risk of contracting genital HPV infection and cervical cancer is influenced by sexual activity. Currently two prophylactic HPV vaccines, Gardasil(r) (Merck, USA) and Cervarix(r) (GlaxoSmithKline, UK), are available and recommended for mass immunization of adolescents. However, these vaccines have limitations as they are expensive and require cold chain storage and trained personnel to administer them by injection. The use of nano or micro particulate vaccines could address most of these limitations as they are stable at room temperature, inexpensive to produce and distribute to resource poor regions, and can be administered orally without the need for adjuvants in the formulation. Also it is possible to increase the efficiency of these particulate vaccines by decorating the surface of the nano or micro particulates with suitable ligands for targeted delivery. Oral vaccines, which can be delivered using particulate formulations, have the added potential to stimulate mucosa-associated lymphoid tissue located in the digestive tract and the gut-associated lymphoid tissue, both of which are important for the induction of effective mucosal response against many viruses. In addition, oral vaccines provide the opportunity to reduce production and administration costs and are very patient compliant. This review elaborately discusses different strategies that can be pursued to develop a nano or micro particulate oral vaccine for HPV induced cancers and other diseases. PMID- 26158288 TI - Puerarin Suppresses Angiotensin II-Induced Cardiac Hypertrophy by Inhibiting NADPH Oxidase Activation and Oxidative Stress-Triggered AP-1 Signaling Pathways. AB - PURPOSE: To examine the effects of puerarin (Pue) on angiotensin II (AngII) induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and oxidative stress-related signaling pathways in the hypertrophic response of cardiomyocytes. METHODS: Primary cardiomyocytes of neonatal C57BL/6J mice were pretreated with Pue (50, 100 MUmol/L) and were then stimulated with AngII 1 MUmol/L. NADPH oxidase activity and reactive oxygen species (ROS) levels were measured by lucigenin-enhanced chemiluminescence assay and flow cytometry. Western blotting was used to detect the distribution of the oxidase subunits, extracellular signal-regulated kinase (ERK1/2) and c-jun N-terminal kinase (JNK1/2) activation, and an electrophoretic mobility shift assay (EMSA) was performed to analyze the DNA binding activity of activator protein-1 (AP-1). Adult C57BL/6J mice were infused with AngII and were administered with Pue (100, 200 mg.kg-1.d-1) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were examined. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were measured, and heart morphometry was assessed. RESULTS: In vitro, Pue dose-dependently blocked the phosphorylation of ERK1/2 and JNK1/2 and eventually abolished AP-1 binding activity through the inhibition of ROS production. Further studies revealed that AngII treatment resulted in increased NADPH oxidase activity, which was suppressed by Pue via the disruption of Rac1 activation and membrane translocation of oxidase subunits. In vivo, Pue attenuated cardiac hypertrophy, as evaluated by decreased HW/BW, LVW/BW, myocyte surface area, and left ventricular wall thickness. CONCLUSIONS: The anti-hypertrophic mechanism of Pue occurred by blocking Rac1-dependent NADPH oxidase activation and downstream redox sensitive AP-1 signaling pathways. PMID- 26158289 TI - Transradial arterial access catheter knots: how to stay out of trouble. AB - Transradial access has nowadays become a standard of care for percutaneous coronary angiography and intervention. This approach has demonstrated significant reduction in bleeding rate, length of hospital stay, and improvement in clinical outcomes when compared to the traditional transfemoral approach. Due to its advantages this new access is also increasingly being used in non-coronary visceral or peripheral interventions. However, this novel approach may lead to severe catheter kinking and twisting and further manipulation may be required to unravel the catheter and avoid complication. Purpose of this technical review is to present the current techniques and trends in preventing and resolving issues related to radial access catheter kinks. PMID- 26158291 TI - MEL-18, a tumor suppressor for aggressive breast cancer. PMID- 26158290 TI - Six stroma-based RNA markers diagnostic for prostate cancer in European-Americans validated at the RNA and protein levels in patients in China. AB - We previously analyzed human prostate tissue containing stroma near to tumor and from cancer-negative tissues of volunteers. Over 100 candidate gene expression differences were identified and used to develop a classifier that could detect nearby tumor with an accuracy of 97% (sensitivity = 98% and specificity = 88%) based on 364 independent test cases from primarily European American cases. These stroma-based gene signatures have the potential to identify cancer patients among those with negative biopsies. In this study, we used prostate tissues from Chinese cases to validate six of these markers (CAV1, COL4A2, HSPB1, ITGB3, MAP1A and MCAM). In validation by real-time PCR, four genes (COL4A2, HSPB1, ITGB3, and MAP1A) demonstrated significantly lower expression in tumor-adjacent stroma compared to normal stroma (p value <= 0.05). Next, we tested whether these expression differences could be extended to the protein level. In IHC assays, all six selected proteins showed lower expression in tumor-adjacent stroma compared to the normal stroma, of which COL4A2, HSPB1 and ITGB3 showed significant differences (p value <= 0.05). These results suggest that biomarkers for diagnosing prostate cancer based on tumor microenvironment may be applicable across multiple racial groups. PMID- 26158293 TI - Unleashing rapamycin in fibrosis. PMID- 26158292 TI - p53 and rapamycin are additive. AB - Mechanistic target of rapamycin (mTOR) is a kinase found in a complex (mTORC1) that enables macromolecular synthesis and cell growth and is implicated in cancer etiology. The rapamycin-FK506 binding protein 12 (FKBP12) complex allosterically inhibits mTORC1. In response to stress, p53 inhibits mTORC1 through a separate pathway involving cell signaling and amino acid sensing. Thus, these different mechanisms could be additive. Here we show that p53 improved the ability of rapamycin to: 1) extend mouse life span, 2) suppress ionizing radiation (IR) induced senescence-associated secretory phenotype (SASP) and 3) increase the levels of amino acids and citric acid in mouse embryonic stem (ES) cells. This additive effect could have implications for cancer treatment since rapamycin and p53 are anti-oncogenic. PMID- 26158295 TI - A2MnU3O11 (A = K, Rb) and Li3.2Mn1.8U6O22: Three New Alkali-Metal Manganese Uranium(VI) Oxides Related to Natrotantite. AB - Single crystals of three new alkali-metal manganese uranium oxides, K2MnU3O11, Rb2MnU3O11, and Li3.2Mn1.8U6O22, have been grown from molten chloride fluxes and structurally characterized by single-crystal X-ray diffraction. The first two compounds crystallize in the trigonal space group, R3c, in the three-dimensional (3D), natrotantite structure composed of alpha-U3O8-topological layers connected via MnO6 octahedra. The Li-containing compound crystallizes in the monoclinic space group, Cc, with a related 3D structure, composed of beta-U3O8-topological sheets connected via irregular MnO7 polyhedra. All three compounds exhibit typical uranyl, UO2(2+), coordination environments consisting of either UO7 pentagonal bipyramids or UO6 flattened octahedra. The lattice parameters of the new oxides are K2MnU3O11, a = 6.8280(2) A, c = 36.8354(17) A; Rb2MnU3O11, a = 6.8407(2) A, c = 37.5520(17) A; and Li3.2Mn1.8U6O22, a = 11.8958(8) A, b = 10.9639(7) A, c = 13.3269(8) A, and beta = 91.442(4) degrees . The magnetic susceptibilities of the K and Rb phases are discussed. PMID- 26158296 TI - Hot-Electron-Induced Highly Efficient O2 Activation by Pt Nanoparticles Supported on Ta2O5 Driven by Visible Light. AB - Aerobic oxidation on a heterogeneous catalyst driven by visible light (lambda >400 nm) at ambient temperature is a very important reaction for green organic synthesis. A metal particles/semiconductor system, driven by charge separation via an injection of "hot electrons (e(hot)(-))" from photoactivated metal particles to semiconductor, is one of the promising systems. These systems, however, suffer from low quantum yields for the reaction (<5% at 550 nm) because the Schottky barrier created at the metal/semiconductor interface suppresses the e(hot)(-) injection. Some metal particle systems promote aerobic oxidation via a non-e(hot)(-)-injection mechanism, but require high reaction temperatures (>373 K). Here we report that Pt nanoparticles (~5 nm diameter), when supported on semiconductor Ta2O5, promote the reaction without e(hot)(-) injection at room temperature with significantly high quantum yields (~25%). Strong Pt-Ta2O5 interaction increases the electron density of the Pt particles and enhances interband transition of Pt electrons by absorbing visible light. A large number of photogenerated e(hot)(-) directly activate O2 on the Pt surface and produce active oxygen species, thus promoting highly efficient aerobic oxidation at room temperature. PMID- 26158294 TI - p53 directly activates cystatin D/CST5 to mediate mesenchymal-epithelial transition: a possible link to tumor suppression by vitamin D3. AB - Cystatin D (CST5) encodes an inhibitor of cysteine proteases of the cathepsin family and is directly induced by the vitamin D receptor (VDR). Interestingly, vitamin D3 exerts tumor suppressive effects in a variety of tumor types. In colorectal cancer (CRC) cells CST5 was shown to mediate mesenchymal-epithelial transition (MET). Interestingly, vitamin D3 was shown to exert tumor suppressive effects in a variety of tumor types, including colorectal cancer (CRC). We recently performed an integrated genomic and proteomic screen to identify targets of the p53 tumor suppressor in CRC cells. Thereby, we identified CST5 as a putative p53 target gene. Here, we validated and characterized CST5 as a direct p53 target gene. After activation of a conditional p53 allele, CST5 was upregulated on mRNA and protein levels. Treatment with nutlin-3a or etoposide induced CST5 in a p53-dependent manner. These regulations were direct, since ectopic and endogenous p53 occupied a conserved binding site in the CST5 promoter region. In addition, treatment with calcitriol, the active vitamin D3 metabolite, and simultaneous activation of p53 resulted in enhanced CST5 induction and increased repression of SNAIL, an epithelial-mesenchymal transition (EMT) inducing transcription factor. Furthermore, CST5 inactivation decreased p53 induced mesenchymal-epithelial transition (MET) as evidenced by decreased inhibition of SNAIL and of migration by p53. Furthermore, CST5 expression was directly repressed by SNAIL. In summary, these results imply CST5 as an important mediator of tumor suppression by p53 in colorectal cancer. In addition, they suggest that a combined treatment activating p53 and the vitamin D3 pathway may function via induction of CST5. PMID- 26158297 TI - Biomechanics of the ski cross start indoors on a customised training ramp and outdoors on snow. AB - An effective start enhances an athlete's chances of success in ski cross competitions. Accordingly, this study was designed to investigate the biomechanics of start techniques used by elite athletes and assess the influence of different start environments. Seven elite ski cross athletes performed starts indoors on a custom-built ramp; six of these also performed starts on an outdoor slope. Horizontal and vertical forces were measured by force transducers located in the handles of the start gate and a 12-camera motion capture system allowed monitoring of the sagittal knee, hip, shoulder, and elbow kinematics. The starting movement involved Pre, Pull, and Push phases. Significant differences between body sides were observed for peak vertical and resultant forces, resultant impulse, and peak angular velocity of the shoulder joint. Significantly lower peak vertical forces (44 N), higher resultant impulse (0.114 Ns/kg), and knee joint range of motion (12 degrees ) were observed indoors. Although movement in the ski cross start is generally symmetrical, asymmetric patterns of force were observed among the athletes. Two different movement strategies, i.e. pronounced hip extension or more accentuated elbow flexion, were utilised in the Pull phase. The patterns of force and movement during the indoor and outdoor starts were similar. PMID- 26158298 TI - Analytical validation of a proliferation-based molecular signature used as a prognostic marker in early stage lung adenocarcinoma. AB - AIMS: The aim of these studies was to validate the analytical performance of a cell cycle progression (CCP) gene signature that provides prognostic information for early stage lung adenocarcinomas. MATERIALS & METHODS: Formalin-fixed paraffin-embedded (FFPE) lung resections were evaluated by quantitative RT-PCR for the expression of 31 target and 15 housekeeper genes comprising the CCP score. RESULTS: The signature had a standard deviation (SD) of 0.06 score units and a dynamic range spanning CCP scores between -13 and 14. The average amplicon efficiencies for target and housekeeper genes were 107% and 105%, respectively. All but one amplicon had a SD <0.5 CT. CONCLUSION: These studies demonstrate that the gene signature is robust and reproducible, making it suitable for use in a clinical setting. PMID- 26158299 TI - Neural Zinc Finger Factor/Myelin Transcription Factor Proteins: Metal Binding, Fold, and Function. AB - Zinc finger (ZF) proteins make up a large family of metalloproteins that contain discrete domains with amino acid ligands (cysteine and histidine) that serve to coordinate zinc in a tetrahedral geometry. Upon zinc coordination, the domains adopt three-dimensional structure. The most well-studied ZFs are the "classical" ZFs, which use a Cys2His2 motif to bind zinc and adopt an antiparallel beta sheet/alpha helical fold. In addition to the classical ZF class, at least 13 other ZF classes, collectively termed nonclassical ZFs, have been identified. These other classes are distinguished by the combination and order of the cysteine and histidine ligands within each domain, the spacing between each ligand (i.e., number and type of amino acid), and the structural architecture that the domain adopts in the presence of zinc. One class of nonclassical ZFs, the neural zinc finger/myelin transcription factor (NZF/MyT) class, contains ZF domains with a Cys2His2Cys ligand set, adopts a fold that consists of a series of loops in the presence of zinc, and functions as transcription factors by binding to and regulating genes that are critical for the development of the central nervous system. This Current Topic focuses on our understanding of the NZF/MyT class of nonclassical ZFs and presents current hypotheses regarding this class' unique mechanism of metal-mediated folding and function. PMID- 26158300 TI - Mathematical Models for Estimating the Risks of Bovine Spongiform Encephalopathy (BSE). AB - When the bovine spongiform encephalopathy (BSE) epidemic first emerged in the United Kingdom in the mid 1980s, the etiology of animal prion diseases was largely unknown. Risk management efforts to control the disease were also subject to uncertainties regarding the extent of BSE infections and future course of the epidemic. As understanding of BSE increased, mathematical models were developed to estimate risk of BSE infection and to predict reductions in risk in response to BSE control measures. Risk models of BSE-transmission dynamics determined disease persistence in cattle herds and relative infectivity of cattle prior to onset of clinical disease. These BSE models helped in understanding key epidemiological features of BSE transmission and dynamics, such as incubation period distribution and age-dependent infection susceptibility to infection with the BSE agent. This review summarizes different mathematical models and methods that have been used to estimate risk of BSE, and discusses how such risk projection models have informed risk assessment and management of BSE. This review also provides some general insights on how mathematical models of the type discussed here may be used to estimate risks of emerging zoonotic diseases when biological data on transmission of the etiological agent are limited. PMID- 26158301 TI - Improving Concordance in Environmental Epidemiology: A Three-Part Proposal. AB - In observational research, evidence is usually derived from multiple studies, and any single result is rarely considered sufficient for public health decision making. Despite more than five decades of research and thousands of studies published, the ability to draw robust conclusions regarding the presence or absence of causal links between specific environmental exposures and human health remains limited. To develop policies that are protective of public health and can withstand scrutiny, agencies need to rely on investigations of satisfactory quality that follow sufficiently concordant protocols in terms of exposure assessment, outcome ascertainment, data analysis, and reporting of results. Absent such concordance, the ability of environmental epidemiology studies to inform decision making is greatly diminished. Systems and tools are proposed here to improve concordance among environmental epidemiology studies. Specifically, working systems in place in other fields of research are critically examined and used as guidelines to develop analogous policies and procedures for environmental epidemiology. A three-part path forward toward more concordant, transparent, and readily accessible environmental epidemiology evidence that parallels ongoing efforts in medical research is proposed. The three parts address methods for improving quality and accessibility of systematic reviews, access to information on ongoing and completed studies, and principles for reporting. The goals are to increase the value of epidemiological research in public health decision making and to stimulate discussions around solutions proposed herein. PMID- 26158302 TI - Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation. AB - High toxicity, poor selectivity, and severe side effects are major drawbacks of anticancer drugs. Various drug delivery systems could be proposed to overcome these limitations. The aim of this study was to fabricate polysaccharide microcontainers (MCs) loaded with thymoquinone (TQ) by a one-step ultrasonication technique and to study their cellular uptake and cytotoxicity in vitro. Two MC fractions with a mean size of 500 nm (MC-0.5) and 2 MUM (MC-2) were prepared and characterized. Uptake of the MCs by mouse melanoma M-3 cells was evaluated in both 2D (monolayer culture) and 3D (multicellular tumor spheroids) models by confocal microscopy, flow cytometry, and fluorimetry. The higher cytotoxicity of the TQ-MC-0.5 sample than the TQ-MC-2 fraction was in good correlation with higher MC-0.5 accumulation in the cells. The MC-0.5 beads were more promising than the MC-2 particles because of a higher cellular uptake in both 2D and 3D models, an enhanced antitumor effect, and a lower nonspecific toxicity. PMID- 26158306 TI - Telomere elongation chooses TERRA ALTernatives. AB - Alternative Lengthening of Telomeres (ALT) mechanisms allow telomerase-negative immortal cells to buffer replicative telomere shortening. ALT is naturally active in a number of human cancers and might be selected upon telomerase inactivation. ALT is thought to operate through homologous recombination (HR) occurring between telomeric repeats from independent chromosome ends. Indeed, suppression of a number of HR factors impairs ALT cell proliferation. Yet, how HR is initiated at ALT telomeres remains elusive. Mounting evidence suggests that the long noncoding telomeric RNA TERRA renders ALT telomeres recombinogenic by forming RNA:DNA hybrids with the telomeric C-rich strand. TERRA and telomeric hybrids act in concert with a number of other factors, including the RNA endoribonuclease RNaseH1 and the single stranded DNA binding protein RPA. The functional interaction network built upon these different players seems indispensable for ALT telomere maintenance, and digging into the molecular details of this previously unappreciated network might open the way to novel avenues for cancer treatments. PMID- 26158307 TI - Role of Hydrogen Bonding and Polyanion Composition in the Formation of Lipid Bilayers on Top of Polyelectrolyte Multilayers. AB - The self-assembly of mixed vesicles of zwitterionic phosphatidylcholine (PC) and anionic phosphatidylserine (PS) phospholipids on top of polyelectrolyte multilayers (PEMs) of poly(allylamine hydrochloride) (PAH), as a polycation, and polystyrenesulfonate (PSS), as a polyanion, is investigated as a function of the vesicle composition by means of the quartz crystal microbalance with dissipation (QCM-D), cryo-transmission electron microscopy (Cryo-TEM), atomic force microscopy (AFM), and atomic force spectroscopy (AFS). Vesicles with molar percentages of PS between 50% and 70% result in the formation of lipid bilayers on top of the PEMs. Vesicles with over 50% of PC or over 80% of PS do not assembly into bilayers. AFS studies performed with a PAH-modified cantilever approaching and retracting from the lipid assemblies reveal that the main interaction between PAH and the lipids takes place through hydrogen bonding between the amine groups of PAH and the carboxylate and phosphate groups of PS and with the phosphate groups of PC. The interaction of PAH with PS is much stronger than with PC. AFS measurements on assemblies with 50% PC and 50% PS revealed similar adhesion forces to pure PS assemblies, but the PAH chains can reorganize much better on the lipids as a consequence of the presence of PC. QCM D experiments show that vesicles with a lipid composition of 50% PC and 50% PS do not form bilayers if PSS is replaced by alginate (Alg) or poly(acrylic acid) (PAA). PMID- 26158308 TI - Antiangiogenic and Anticancer Properties of Bifunctional Ruthenium(II)-p-Cymene Complexes: Influence of Pendant Perfluorous Chains. AB - Two bifunctional ruthenium(II)-p-cymene complexes with perfluorinated side chains, attached via pyridine ligands, have been evaluated in a series of in vitro and in vivo assays. Their effects on human endothelial (ECRF24 and HUVEC) cells, noncancerous human embryonic kidney (HEK-293) cells, and various human tumor cells were investigated. The complex with the shorter chain, 1, inhibits the proliferation of the tumor cell lines and ECRF24, whereas 2 selectively inhibits ECRF24 and HUVEC proliferation. Neither inhibits the migration of ECRF24 cells whereas both compounds inhibit sprout formation in HUVEC cells. Using three preclinical models, i.e., vasculature formation in the chorioallantoic membrane (CAM) of the chicken embryo, human A2780 ovarian carcinoma tumors xenografted on the CAM, and human LS174T colorectal adenocarcinoma tumors grown in athymic mice, the angiostatic and anticancer activities of these two complexes were studied. Overall, 1 inhibited tumor growth predominantly through an anticancer effect whereas 2 inhibited tumor growth predominately via an antiangiogenic mechanism. PMID- 26158309 TI - Seat belt use and fit among drivers aged 75 years and older in their own vehicles. AB - OBJECTIVE: This article aims to describe seat belt wearing patterns and quality of seat belt fit among drivers aged 75 years and older. A secondary aim is to explore associations between body shape, comfort, and seat belt use patterns. METHODS: This is an observation and survey study of a cohort of 380 drivers aged 75 years and over. During home visits, photographs were taken of the drivers in their vehicles for later analysis of belt fit and a short survey was also administered to collect demographic data and information about seat belt use and comfort. Seat belt fit and use of belt and seat accessories were analyzed from the photographs. RESULTS: Data from 367 participants with photographs were analyzed. Whereas 97% reported using a seat belt and 90% reported their seat belt to be comfortable, 21% reported repositioning their seat belt to improve comfort. Good sash and lap belt fit were achieved in 53 and 59% of participants, respectively, but only 35% achieved overall good fit. Both poor sash and lap belt fit were observed in 23% of participants. Drivers who were in the obese category had over twice the odds (95% confidence interval [CI], 1.2-4.1) of having a poor lap belt fit than those in the normal body mass index [BMI] range, and drivers who were overweight had 1.8 times the odds (95% CI, 1.1-2.9) of having poor lap belt fit. Older females also had twice the odds (95% CI, 1.3-3.5) of poor lap belt fit compared to older males, regardless of BMI. Sash belt fit did not vary significantly by BMI, stature, or gender. However older drivers who reported that they had not made any adjustments to the D-ring height had 1.7 times the odds of having poor sash belt fit than those who made adjustments (1.2-2.9). Females were 7.3 times more likely to report comfort problems than males (95% CI, 3.2, 16.3) but there was no association between reported comfort and BMI or seat belt fit. Drivers who reported comfort problems had 6 times the odds (3.2-13.6) of also reporting active repositioning of the belt. CONCLUSIONS: The results suggest that older drivers face challenges in achieving comfortable and correct seat belt fit. This may have a negative impact on crash protection. Belt fit problems appear to be associated with body shape, particularly high BMI and gender. There is a need for further investigation of comfort accessories; in the interim, older drivers and occupants should be encouraged to use features such as D-ring adjusters to improve sash belt fit. PMID- 26158312 TI - Bioactive compounds from the endophytic fungus Fusarium proliferatum. AB - The crude extract of an endophytic fungus isolated from Syzygium cordatum and identified as Fusarium proliferatum showed 100% cytotoxicity against the brine shrimp Artemia salina at 100 MUg/mL. Seven coloured, biologically active metabolites - including ergosta-5,7,22-trien-3beta-ol, nectriafurone-8-methyl ether, 9-O-methyl fusarubin, bostrycoidin, bostrycoidin-9-methyl ether and 8 hydroxy-5,6-dimethoxy-2-methyl-3-(2-oxo-propyl)-1,4-naphthoquinone- were isolated from the extract. PMID- 26158313 TI - Generation and Ring Opening of Aziridines in Telescoped Continuous Flow Processes. AB - A simple method for the preparation of a variety of N-sulfonyl aziridines (10 examples) from 1,2-amino alcohols under continuous flow conditions is described. Using flow based methods, the aziridines can be further ring opened with oxygen, carbon, and halide nucleophiles or ring expanded to imidazolines by Lewis acid promoted reaction with nitriles. Telescoping the aziridine generation and ring opening steps together in a microfluidic reactor allows the chemistry to be undertaken with limited exposure to the potentially hazardous aziridine intermediates. PMID- 26158314 TI - Supramolecular Rotor and Translator at Work: On-Surface Movement of Single Atoms. AB - A supramolecular nanostructure composed of four 4-acetylbiphenyl molecules and self-assembled on Au (111) was loaded with single Au adatoms and studied by scanning tunneling microscopy at low temperature. By applying voltage pulses to the supramolecular structure, the loaded Au atoms can be rotated and translated in a controlled manner. The manipulation of the gold adatoms is driven neither by mechanical interaction nor by direct electronic excitation. At the electronic resonance and driven by the tunneling current intensity, the supramolecular nanostructure performs a small amount of work of about 8 * 10(-21) J, while transporting the single Au atom from one adsorption site to the next. Using the measured average excitation time necessary to induce the movement, we determine the mechanical motive power of the device, yielding about 3 * 10(-21) W. PMID- 26158318 TI - Multigenerational Dissociation: A Framework for Building Narrative. AB - This paper presents the concept of Multigenerational Dissociation (MGD), a behavior pattern that occurs in families in which violence and abuse are re enacted from one generation to the next, accompanied by denial that the trauma occurred, or if it did, that it was destructive. While revictimization, reenactment, and the intergenerational transmission of trauma are discussed extensively in the literature, MGD helps to view them within a broad historical framework. This is useful for conceptualizing cases therapeutically, and it can also contribute to research on dissociation and recovered memories of trauma and abuse by demonstrating the value of narrative clinical data. Case material is used to illustrate how MGD occurs in people's lives and affects their memories, demonstrating how it becomes a frame within which to convey the dynamics of how traumatic experiences are remembered. This also demonstrates that when clinicians contribute their own narrative data to research on traumatic memory, the science is more accurate, relevant, and comprehensible to clinical and nonclinical researchers. PMID- 26158320 TI - Unexpected Ultrafast Silver Ion Reduction: Dynamics Driven by the Solvent Structure. AB - Picosecond pulse radiolysis measurements have been performed in neutral and highly acidic aqueous solutions containing silver ions at different concentrations. Silver ion reduction is used to understand the ultrafast chemistry of irradiated water and aqueous solutions. The absorption band measured at the end of the 7-ps electron pulses has an intense band with a maximum at 360 nm due to the formation of silver atoms. Kinetics shows that the amount of silver atom formed at the end of the electron pulse in phosphoric acid solutions is greater than that in neutral water. This unexpectedly high yield of silver atom formation cannot be explained solely by the reaction between silver ions and solvated electrons in neutral solutions nor by the reaction with hydrogen atoms in phosphoric acid solutions. To explain the observed ultrafast reduction of silver ions, the presolvated electron, be it free or paired to the hydronium cation, must react very quickly with a silver ion, potentially competing with geminate recombination of the electron and its sibling radical cation. PMID- 26158319 TI - DNA vaccines targeting heavy chain C-terminal fragments of Clostridium botulinum neurotoxin serotypes A, B, and E induce potent humoral and cellular immunity and provide protection from lethal toxin challenge. AB - Botulinum neurotoxins (BoNTs) are deadly, toxic proteins produced by the bacterium Clostridium botulinum that can cause significant diseases in humans. The use of the toxic substances as potential bioweapons has raised concerns by the Centers for Disease Control and Prevention and the United States Military. Currently, there is no licensed vaccine to prevent botulinum intoxication. Here we present an immunogenicity study to evaluate the efficacy of novel monovalent vaccines and a trivalent cocktail DNA vaccine targeting the heavy chain C terminal fragments of Clostridium botulinum neurotoxin serotypes A, B, and E. These synthetic DNA vaccines induced robust humoral and polyfunctional CD4(+) T cell responses which fully protected animals against lethal challenge after just 2 immunizations. In addition, naive animals administered immunized sera mixed with the lethal neurotoxin were 100% protected against intoxication. The data demonstrate the protective efficacy induced by a combinative synthetic DNA vaccine approach. This study has importance for the development of vaccines that provide protective immunity against C. botulinum neurotoxins and other toxins. PMID- 26158321 TI - Validated Method for the Characterization and Quantification of Extractable and Nonextractable Ellagitannins after Acid Hydrolysis in Pomegranate Fruits, Juices, and Extracts. AB - Pomegranates are one of the main highly valuable sources of ellagitannins. Despite the potential health benefits of these compounds, reliable data on their content in pomegranates and derived extracts and food products is lacking, as it is usually underestimated due to their complexity, diversity, and lack of commercially available standards. This study describes a new method for the analysis of the extractable and nonextractable ellagitannins based on the quantification of the acid hydrolysis products that include ellagic acid, gallic acid, sanguisorbic acid dilactone, valoneic acid dilactone, and gallagic acid dilactone in pomegranate samples. The study also shows the occurrence of ellagitannin C-glycosides in pomegranates. The method was optimized using a pomegranate peel extract. To quantify nonextractable ellagitannins, freeze-dried pomegranate fruit samples were directly hydrolyzed with 4 M HCl in water at 90 degrees C for 24 h followed by extraction of the pellet with dimethyl sulfoxide/methanol (50:50, v/v). The method was validated and reproducibility was assessed by means of an interlaboratory trial, showing high reproducibility across six laboratories with relative standard deviations below 15%. Their applicability was demonstrated in several pomegranate extracts, different parts of pomegranate fruit (husk, peels, and mesocarp), and commercial juices. A large variability has been found in the ellagitannin content (150-750 mg of hydrolysis products/g) and type (gallagic acid/ellagic acid ratios between 4 and 0.15) of the 11 pomegranate extracts studied. PMID- 26158322 TI - Bioinspired toughening mechanism: lesson from dentin. AB - Inspired by the unique microstructure of dentin, in which the hard peritubular dentin surrounding the dentin tubules is embedded in the soft intertubular dentin, we explore the crack propagation in the bioinspired materials with fracture process zone possessing a dentin-like microstructure, i.e. the composite structure consisting of a soft matrix and hard reinforcements with cylindrical voids. A micromechanical model under small-scale yielding conditions is developed, and numerical simulations are performed, showing that the rising resistant curve (R-curve) is observed for crack propagation caused by the plastic collapse of the intervoid ligaments in the fracture process zone. The dentin-like microstructure in the fracture process zone exhibits enhanced fracture toughness, compared with the case of voids embedded in the homogeneous soft matrix. Further computational simulations show that the dentin-like microstructure can retard void growth, thereby promoting fracture toughness. The typical fracture mechanism of the bioinspired materials with fracture process zone possessing the dentin like structure is void by void growth, while it is the multiple void interaction in the case of voids in the homogeneous matrix. Based on the results, we propose a bioinspired material design principle, which is that the combination of a hard inner material encompassing voids and a soft outer material in the fracture process zone can give rise to exceptional fracture toughness, achieving damage tolerance. It is expected that the proposed design principle could shed new light on the development of novel man-made engineering materials. PMID- 26158323 TI - Insight into Trypsin Miscleavage: Comparison of Kinetic Constants of Problematic Peptide Sequences. AB - Trypsin, a high fidelity protease, is the most widely used enzyme for protein digestion in proteomic research. Optimal digestion conditions are well-known and so are the expected cleavage products. However, missed cleavage sites are frequently observed when acidic amino acids, aspartic and glutamic acids, are present near the cleavage site. Also, the sequence motifs with successive lysine and/or arginine residues represent a source of missed cleaved sites. In spite of an adverse role of missed cleaved peptides on proteomic research, the digestion kinetics of these problematic sequences is not well-known. In this work, synthetic peptides with various sequence motifs were used as trypsin substrates. Cleavage products were analyzed with reversed-phase high performance liquid chromatography, and the kinetic constants for selected missed cleavage sites were calculated. Relative digestion speed for lysine and arginine sites is compared, including the digestion motifs flanked with aspartic and glutamic acid. Our findings show that DK and DTR motifs are cleaved by trypsin with 3 orders of magnitude lower speed than the arginine site. These motifs are likely to produce missed cleavage peptides in protein tryptic digests even at prolonged digestion times. PMID- 26158324 TI - Presenting TLM's First Editors' Choice Award. PMID- 26158325 TI - Exam Success at Undergraduate and Graduate-Entry Medical Schools: Is Learning Style or Learning Approach More Important? A Critical Review Exploring Links Between Academic Success, Learning Styles, and Learning Approaches Among School Leaver Entry ("Traditional") and Graduate-Entry ("Nontraditional") Medical Students. AB - PHENOMENON: The literature on learning styles over many years has been replete with debate and disagreement. Researchers have yet to elucidate exactly which underlying constructs are measured by the many learning styles questionnaires available. Some academics question whether learning styles exist at all. When it comes to establishing the value of learning styles for medical students, a further issue emerges. The demographics of medical students in the United Kingdom have changed in recent years, so past studies may not be applicable to students today. We wanted to answer a very simple, practical question: what can the literature on learning styles tell us that we can use to help today's medical students succeed academically at medical school? APPROACH: We conducted a literature review to synthesise the available evidence on how two different aspects of learning-the way in which students like to receive information in a learning environment (termed learning "styles") and the motivations that drive their learning (termed learning "approaches")-can impact on medical students' academic achievement. FINDINGS: Our review confirms that although learning "styles" do not correlate with exam performance, learning "approaches" do: those with "strategic" and "deep" approaches to learning (i.e., motivated to do well and motivated to learn deeply respectively) perform consistently better in medical school examinations. Changes in medical school entrant demographics in the past decade have not altered these correlations. Optimistically, our review reveals that students' learning approaches can change and more adaptive approaches may be learned. Insights: For educators wishing to help medical students succeed academically, current evidence demonstrates that helping students develop their own positive learning approach using "growth mind-set" is a more effective (and more feasible) than attempting to alter students' learning styles. This conclusion holds true for both "traditional" and graduate-entry medical students. PMID- 26158326 TI - Patients' Attitudes Toward Medical Student Participation Across Specialties: A Systematic Review. AB - Phenomenon: Medical students commonly participate in patient care in a variety of different settings. However, a systematic review of patients' attitudes toward medical student participation across specialties has not been performed. APPROACH: The authors searched 7 databases (CINAHL, Cochrane Library, ERIC, MEDLINE, PsycINFO, Scopus, and Web of Science) between January 1, 1999, and August 5, 2014. Two authors independently screened the results and selected articles that were written in English, were published in a peer-reviewed journal, and used a structured or semistructured survey or interview to determine patients' attitudes toward medical student participation in their care. Study quality was assessed using the Medical Education Research Study Quality Instrument. FINDINGS: Fifty-nine studies were included. Average study quality was low. Sixty-one unique evaluation instruments were used, and 34 instruments (56%) lacked validity data. Patient satisfaction was not significantly affected by medical student participation. However, patients' acceptance of medical student participation varied widely between studies and depended on the type of participation. The most common reason for acceptance was a desire to contribute to the education of others, and the most common reason for refusal was concerns about privacy. Minorities were more likely to refuse medical student participation. Patients preferred to be informed before medical students participated in their care. Insights: Patient satisfaction is not significantly affected by medical student participation. However, patient satisfaction may be a poor surrogate marker of patients' acceptance of medical students. Future research should employ validated evaluation instruments to further explore patients' attitudes toward medical student participation. PMID- 26158327 TI - Lesbian, Gay, Bisexual, and Transgender Patient Care: Medical Students' Preparedness and Comfort. AB - Phenomenon: Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant barriers in accessing appropriate and comprehensive medical care. Medical students' level of preparedness and comfort caring for LGBT patients is unknown. APPROACH: An online questionnaire (2009-2010) was distributed to students (n = 9,522) at 176 allopathic and osteopathic medical schools in Canada and the United States, followed by focus groups (2010) with students (n = 35) at five medical schools. The objective of this study was to characterize LGBT related medical curricula, to determine medical students' assessments of their institutions' LGBT-related curricular content, and to evaluate their comfort and preparedness in caring for LGBT patients. FINDINGS: Of 9,522 survey respondents, 4,262 from 170 schools were included in the final analysis. Most medical students (2,866/4,262; 67.3%) evaluated their LGBT-related curriculum as "fair" or worse. Students most often felt prepared addressing human immunodeficiency virus (HIV; 3,254/4,147; 78.5%) and non-HIV sexually transmitted infections (2,851/4,136; 68.9%). They felt least prepared discussing sex reassignment surgery (1,061/4,070; 26.1%) and gender transitioning (1,141/4,068; 28.0%). Medical education helped 62.6% (2,669/4,262) of students feel "more prepared" and 46.3% (1,972/4,262) of students feel "more comfortable" to care for LGBT patients. Four focus group sessions with 29 students were transcribed and analyzed. Qualitative analysis suggested students have significant concerns in addressing certain aspects of LGBT health, specifically with transgender patients. Insights: Medical students thought LGBT-specific curricula could be improved, consistent with the findings from a survey of deans of medical education. They felt comfortable, but not fully prepared, to care for LGBT patients. Increasing curricular coverage of LGBT-related topics is indicated with emphasis on exposing students to LGBT patients in clinical settings. PMID- 26158328 TI - Family Medicine in Egypt From Medical Students' Perspective: A Nationwide Survey. AB - PHENOMENON: Attitudes of medical students toward family medicine as a specialty choice can provide information on the future supply of family physicians. Due to the current worldwide shortage of family physicians, these attitudes, with their subsequent effects on the state and dynamics of the healthcare system, are important to investigate. APPROACH: A web-based questionnaire was sent to 600 medical students, selected by a systematic random sampling technique, in 7 Egyptian medical schools. Participants were surveyed to assess their perception of the family medicine specialty as a future career and explore the impact of different factors, including undergraduate family medicine clerkships, on their attitudes toward family medicine. FINDINGS: We had a response rate of 75.2% (n = 451). Although 90.7% of students believed in the vital role that family medicine can play in Egypt's healthcare system, only 4.7% showed an intention to choose it as a future career. Students choosing family medicine as a first-career choice were more likely to have a prior contact with family physicians as consumers. Exposure to an undergraduate family medicine curriculum was associated with increased knowledge about family medicine but not the intentions to pursue it as a career. INSIGHTS: Medical students in Egypt have a positive perception of family medicine as an important specialty but low interest in its choice as a future career. PMID- 26158329 TI - Going Paperless? Issues in Converting a Surgical Assessment Tool to an Electronic Version. AB - CONSTRUCT: The competence of a trainee to perform a surgical procedure was assessed using an electronic tool. BACKGROUND: "Going paperless" in healthcare has received significant attention over the past decades given the numerous potential benefits of converting to electronic health records. Not surprisingly, medical educators have also considered the potential benefits of electronic assessments for their trainees. What literature exists on the transition from paper-based to electronic-based assessments suggests a positive outcome. In contrast, work done examining the transition to and implementation of electronic health records has noted that hospitals who have implemented these systems have not gone paperless despite the benefits of doing so. APPROACH: This study sought to transition a paper-based assessment tool, the Ottawa Surgical Competency Operating Room Evaluation (which has strong evidence for validity) to an electronic version, in three surgical specialties (Orthopedic Surgery, Urology, General Surgery). However, as the project progressed, it became necessary to change the focus of the study to explore the issues of transitioning to a paperless assessment tool as we identified an extremely low participation rate. RESULTS: Over the first 3 months 440 assessment cases were logged. However, only a small portion of these cases were assessed using the electronic tool (Orthopedic Surgery = 16%, Urology = 5%, General Surgery = 0%). Participants identified several barriers in using the electronic assessment tool such as increased time compared to the paper version and technological issues related to the log-in procedure. CONCLUSIONS: Essentially, users want the tool to be as convenient as paper. This is consistent with research on electronic health records implementation but different from previous work in medical education. Thus, we believe our study highlights an important finding. Transitioning from a paper-based assessment tool to an electronic one is not necessarily a neutral process. Consideration of potential barriers and finding solutions to these barriers will be necessary in order to realize the many benefits of electronic assessments. PMID- 26158330 TI - Standard Setting Methods for Pass/Fail Decisions on High-Stakes Objective Structured Clinical Examinations: A Validity Study. AB - CONSTRUCT: Authentic standard setting methods will demonstrate high convergent validity evidence of their outcomes, that is, cutoff scores and pass/fail decisions, with most other methods when compared with each other. BACKGROUND: The objective structured clinical examination (OSCE) was established for valid, reliable, and objective assessment of clinical skills in health professions education. Various standard setting methods have been proposed to identify objective, reliable, and valid cutoff scores on OSCEs. These methods may identify different cutoff scores for the same examinations. Identification of valid and reliable cutoff scores for OSCEs remains an important issue and a challenge. APPROACH: Thirty OSCE stations administered at least twice in the years 2010-2012 to 393 medical students in Years 2 and 3 at Aga Khan University are included. Psychometric properties of the scores are determined. Cutoff scores and pass/fail decisions of Wijnen, Cohen, Mean-1.5SD, Mean-1SD, Angoff, borderline group and borderline regression (BL-R) methods are compared with each other and with three variants of cluster analysis using repeated measures analysis of variance and Cohen's kappa. RESULTS: The mean psychometric indices on the 30 OSCE stations are reliability coefficient = 0.76 (SD = 0.12); standard error of measurement = 5.66 (SD = 1.38); coefficient of determination = 0.47 (SD = 0.19), and intergrade discrimination = 7.19 (SD = 1.89). BL-R and Wijnen methods show the highest convergent validity evidence among other methods on the defined criteria. Angoff and Mean-1.5SD demonstrated least convergent validity evidence. The three cluster variants showed substantial convergent validity with borderline methods. CONCLUSIONS: Although there was a high level of convergent validity of Wijnen method, it lacks the theoretical strength to be used for competency-based assessments. The BL-R method is found to show the highest convergent validity evidences for OSCEs with other standard setting methods used in the present study. We also found that cluster analysis using mean method can be used for quality assurance of borderline methods. These findings should be further confirmed by studies in other settings. PMID- 26158331 TI - Assessing Medical Students' Tobacco Dependence Treatment Skills Using a Detailed Behavioral Checklist. AB - CONSTRUCT: This article describes the development and implementation of an assessment intended to provide objective scores that would be valid indications of medical students' abilities to counsel patients about tobacco dependence. BACKGROUND: Assessing medical students' advanced communication skills, particularly in the context of providing tobacco-dependence treatment, consistently and accurately is challenging; doing so across multiple medical schools is even more difficult. APPROACH: Ten medical schools implemented a tobacco-dependence treatment case as part of an Objective Structured Clinical Examination for 3rd-year medical students. A 33-item checklist with detailed criteria and examples was developed for scoring students' performances. Trained coders viewed and coded 660 videotaped encounters; approximately 10% also were coded by the coding supervisor to check accuracy. RESULTS: Average time required to code an encounter was approximately 31 minutes; accuracy (i.e., agreement with the gold standard coder) was excellent. Overall, students performed an average of 1 in 4 of the 33 behaviors included on the checklist, and only 1 in 10 discussed setting a quit date. Most students (almost 9 in 10) asked how much the patient smoked in a day, and just over 7 in 10 informed the patient that the cough was due to smoking. CONCLUSIONS: The authors developed and implemented a rigorous assessment that will be used to evaluate medical students' tobacco-dependence treatment skills. Operationalizing the specific counseling behaviors, training coders to accurately capture students' performances using a structured checklist, and conducting the coding all required substantial time commitments but will provide confidence in the objectivity of the assessment results. In addition, this assessment can be used to provide formative information on medical students' tobacco-dependence treatment skills and to tailor ongoing training for medical students in this area. PMID- 26158332 TI - Content and Rationale of Junior and Senior Preceptors Responding to Residents' Educational Needs Revisited. AB - THEORY: Feedback and debriefing, as portrayed in expertise development and self assessment, play critical roles in providing residents with useful information to foster their progress. HYPOTHESES: Prior work has shown that clinical preceptors' use of conceptual frameworks (CFs; ways of thinking based on theories, best practices, or models) while giving feedback to residents was positively associated with a greater diversity of responses. Also, senior preceptors produced more responses, used more CFs, and asked more probing-challenging questions than junior preceptors. The purpose was to confirm the generalization of these initial findings with a broader and better defined sample of preceptors. METHOD: We conducted a mixed-method study with 20 junior and 20 senior preceptors in a controlled environment to analyze their responses and rationales to residents' educational needs as portrayed in 6 written vignettes. The preceptors were recruited from 3 primary care specialties preceptors (family medicine, internal medicine, pediatrics) of the 3 French-speaking faculties of medicine in Quebec, Canada. RESULTS: The preceptors increased the 2012 list of response topics (96 to 126) and doubled the number of distinct CFs (16 to 32). The junior and senior preceptors expressed the same number and diversity of CFs. On average, senior preceptors asked more clarification questions and reflected more than juniors on the learning process that occurs during case discussions. Preceptor specialty and prior training in medical education did not influence the number and diversity of responses and CFs, except that preceptors with prior training generated more responses per vignette and were more reflective. Senior preceptors had a stronger positive relationship between the number of total and distinct CFs and the number of responses than the juniors. CONCLUSIONS: Although senior preceptors did not give more responses or use more CFs compared to the prior study, they continue to probe residents more and reflected more. The positive relationship between responses and CFs has important implications for faculty development and calls for more research to better understand the specific contribution of CFs to feedback. PMID- 26158333 TI - Introducing Final-Year Medical Students to Pocket-Sized Ultrasound Imaging: Teaching Transthoracic Echocardiography on a 2-Week Anesthesia Rotation. AB - PROBLEM: The availability of less expensive and smaller ultrasound machines has enabled the use of ultrasound in virtually all major medical/surgical disciplines. Some medical schools have incorporated point-of-care ultrasound training into their undergraduate curriculum, whereas many postgraduate programs have made ultrasound training a standard. The Chinese University of Hong Kong has charged its Department of Anaesthesia and Intensive Care to spearhead the introduction of ultrasound into the final-year medical curriculum by introducing handheld transthoracic echocardiography as part of perioperative assessment. INTERVENTION: All 133 final-year students completed a 2-week anesthesia rotation, which began with a half-day session consisting of a lecture and hands-on practice session during which they learned 9 basic transthoracic echocardiography views using 4 basic ultrasound probe positions. CONTEXT: Each student was required to perform a transthoracic echocardiography-examine under supervision of 1 patient/week for 2 weeks, and their results were compared against that of the supervisor's. Most patients were elective cardiac surgery patients. One long question on transthoracic echocardiography was included in their end-of-year surgery examination paper. Students provided feedback on their experience. OUTCOME: Most students learned the basic transthoracic echocardiography views fairly efficiently and had variable, though generally favorable, success rates in identifying obvious cardiac anomalies, including use of color Doppler. A few common mistakes were identified but were easily correctable. Logistics for mobilizing enough bedside supervision were challenging. Students reported positive feedback on the teaching initiative. LESSONS LEARNED: We were able to execute a successful short training course on transthoracic echocardiography during the final-year medical degree anesthesia rotation. Our initiative may set an example for other clinical departments to design similar courses pertinent to their specialties and syllabuses. PMID- 26158334 TI - Innovation in Indigenous Health and Medical Education: The Leaders in Indigenous Medical Education (LIME) Network as a Community of Practice. AB - PROBLEM: The Leaders in Indigenous Medical Education (LIME) Network aims to improve the quality and effectiveness of Indigenous health in medical education as well as best practice in the recruitment, retention, and graduation of Indigenous medical students. INTERVENTION: In this article we explore the utility of Etienne Wenger's "communities of practice" (CoP) concept in providing a theoretical framework to better understand the LIME Network as a form of social infrastructure to further knowledge and innovation in this important area of health care education reform. CONTEXT: The Network operates across all medical schools in Australia and New Zealand. OUTCOME: Utilizing a model of evaluation of communities of practice developed by Fung-Kee-Fung et al., we seek to analyze the outcomes of the LIME Network as a CoP and assess its approach and contribution to improving the implementation of Indigenous health in the medical curriculum and the graduation of Indigenous medical students. LESSONS LEARNED: By reflecting on the Network through a community of practice lens, this article highlights the synthesis between the LIME Network and Wenger's theory and provides a framework with which to measure Network outputs. It also posits an opportunity to better capture the impact of Network activities into the future to ensure that it remains a relevant and sustainable entity. PMID- 26158335 TI - One Model of Residency Journal Clubs With Multifaceted Support. AB - PROBLEM: The field of medical education is represented by a fairly wide variety of models for utilizing journal clubs as an effective teaching tool, each with varying levels of empirical support. Our own prior attempts at developing and implementing an effective journal club required improvements. INTERVENTION: Our intervention consisted of an innovative, effective journal club model that has more well-defined elements that are readily adaptable for other residency programs. The collective strategies were based on the previous literature and our own experiences. CONTEXT: Our intervention was implemented in a department of psychiatry within a university-based medical school. Study participants came from a psychiatry department's residency programs (N = 36) during academic year 2011 2012 with senior residents having the option to attend journal club. Using a multifaceted approach, measures included attendance, presession quizzes, postsession evaluations, and a final postcourse evaluation of 11 dimensions (e.g., goals, objectives). OUTCOME: Thirty-one (86%) trainees attended journal club-a substantial increase from previous years. The presession-quiz median was 4.4 total correct out of 6 questions (range = 3.3-5.3), indicating that the articles were generally read before the session. The postsession-evaluation median was 4.6 (1-5 scale, 5 the highest; range = 4.1-4.8), indicating sessions were well received. The final postcourse-evaluation overall mean was 3.9 (1-5 scale, 5 the highest; subscale M range = 3.4-4.5). Qualitative and quantitative analyses of the postcourse evaluation indicated the following positive aspects: educational objectives generally met, overall structured format, quality of discussions, individuals involved (e.g., course directors, trainees, faculty facilitators), and availability of food. Areas of possible improvement included time management within the sessions, more contemporary and clinically relevant articles, consistency in faculty moderators, and evaluation process. Engagement in learning appeared to have been dramatically increased through five strategies: (a) meaningful incentives; (b) assigned, engaged consistently prepared faculty; (c) meaningful evaluation; (d) prejournal club preparations that helped residents assimilate critical appraisal with time-and-task-management skills; and (e) a planning group that developed and improved curricula and instruction to meet the objectives of the course. LESSONS LEARNED: Overall, effective, and successful journal clubs require systematic planning, implementation, modification, and refinement. PMID- 26158336 TI - Physician Depression and Suicide: A Shared Responsibility. AB - ISSUE: Although the exact number is often disputed, it has been reported that approximately 300 to 400 physicians in the United States take their own lives annually. Despite calls from key interest groups for prevention and treatment protocols of physician suicide, little systematic change has taken place. EVIDENCE: Research on suicide risk factors among physicians has expanded. Increasing reports are surfacing that highlight suicidal ideation and depression in medical school, residency training, and later professional practice. IMPLICATIONS: The purpose of this article is to draw attention to the problem of physician suicide with an emphasis on the role of medical education. Multiple accreditation bodies should be involved to effect a change in physician suicide prevalence. Thirty years have demonstrated that without mandates, large-scale change will not occur. We adapted some of the 2012 National Strategy for Suicide Prevention goals to medical education as a guide. PMID- 26158339 TI - Type II Inhibitors Targeting CDK2. AB - Kinases can switch between active and inactive conformations of the ATP/Mg(2+) binding motif DFG, which has been explored for the development of type I or type II inhibitors. However, factors modulating DFG conformations remain poorly understood. We chose CDK2 as a model system to study the DFG in-out transition on a target that was thought to have an inaccessible DFG-out conformation. We used site-directed mutagenesis of key residues identified in structural comparisons in conjunction with biochemical and biophysical characterization of the generated mutants. As a result, we identified key residues that facilitate the DFG-out movement, facilitating binding of type II inhibitors. However, surprisingly, we also found that wild type CDK2 is able to bind type II inhibitors. Using protein crystallography structural analysis of the CDK2 complex with an aminopyrimidine phenyl urea inhibitor (K03861) revealed a canonical type II binding mode and the first available type II inhibitor CDK2 cocrystal structure. We found that the identified type II inhibitors compete with binding of activating cyclins. In addition, analysis of the binding kinetics of the identified inhibitors revealed slow off-rates. The study highlights the importance of residues that may be distant to the ATP binding pocket in modulating the energetics of the DFG-out transition and hence inhibitor binding. The presented data also provide the foundation for a new class of slow off-rate cyclin-competitive CDK2 inhibitors targeting the inactive DFG-out state of this important kinase target. PMID- 26158340 TI - Pd-Catalyzed Highly Regio- and Stereoselective Formation of C-C Double Bonds: An Efficient Method for the Synthesis of Benzofuran-, Dihydrobenzofuran-, and Indoline-Containing Alkenes. AB - A highly regio- and stereoselective C-C double bond formation reaction via Pd catalyzed Heck-type cascade process with N-tosylhydrazones has been developed. Various N-tosylhydrazones derived from both ketones and aldehydes are found to be efficient substrates to provide di- and trisubstituted olefins with high regio- and stereoselectivity. Furthermore, this reaction has a good functional group tolerance and different benzofuran-, dihydrobenzofuran-, and indoline-containing alkene products were obtained with high selectivity. PMID- 26158341 TI - Relevance Vector Machines: Sparse Classification Methods for QSAR. AB - Sparse machine learning methods have provided substantial benefits to quantitative structure property modeling, as they make model interpretation simpler and generate models with improved predictivity. Sparsity is usually induced via Bayesian regularization using sparsity-inducing priors and by the use of expectation maximization algorithms with sparse priors. The focus to date has been on using sparse methods to model continuous data and to carry out sparse feature selection. We describe the relevance vector machine (RVM), a sparse version of the support vector machine (SVM) that is one of the most widely used classification machine learning methods in QSAR and QSPR. We illustrate the superior properties of the RVM by modeling eight data sets using SVM, RVM, and another sparse Bayesian machine learning method, the Bayesian regularized artificial neural network with Laplacian prior (BRANNLP). We show that RVM models are substantially sparser than the SVM models and have similar or superior performance to them. PMID- 26158342 TI - [Development and Implementation of a Comprehensive Health Management System (Fit for Work and Life) for Employees of a University Hospital - A Practice Report]. AB - Background: Due to the increase of sick leave, prolonging working life and the prediction of shortage of skilled workers in the future, health management systems are continuously gaining importance. Employees in a University Hospital are exposed to particular stress factors, which are also reflected in a higher than average amount of sick leave. Against this background, the project "Fit for Work and Life" (FWL) was developed and implemented by the Hannover Medical School (MHH). Aims: FWL aims to maintain, improve or recover the work ability of employees by offering both preventive and rehabilitative treatments. A second goal is to significantly reduce the days of sick leave. Methods: The project was jointly developed and implemented by five MHH departments and the DRV Braunschweig-Hannover (DRV BS-H) according to previously defined principles. It was scientifically evaluated by the following outcomes: average days of sick leave, work ability (WAI), quality of life (SF-36, WHOQOL), coping strategies (FERUS) and effort-reward imbalance (ERI). Results and Conclusions: So far, this project is unique in its concept. It has been successfully implemented in the organisational structures of the MHH. 376 employees have registered during the first project year. Up to now, 182 participants have completed their individual programmes. The results show that 60.4% of employees have moderate to poor WAI values. The average of the mental summary scale of the SF-36 was 44.9, indicating a high workload. PMID- 26158343 TI - [Quitting Attempts and Utilisation of Smoking Cessation Aids among Smokers in Germany: Results from the 2012 Epidemiological Survey of Substance Abuse]. AB - Aim: This study presents current data on smoking cessation and usage of smoking cessation aids among smokers in a representative sample of German smokers. Data of 2012 will be compared with data of the year 2000. Methods: The sample of the 2012 Epidemiological Survey of Substance Abuse (ESA) was randomly drawn from population registers and consisted of 9 084 individuals aged 18-64 years. A mixed mode design including questionnaires, telephone and Internet interviews was applied. The response rate was 53,6%. Number of smoking cessation attempts and usage of smoking cessation aids were assessed among actual and former smokers. Results: Of the 4 261 persons who had smoked in their lifetime 54,1% are actual and 45,9% former smokers. Among actual smokers 64,5% have tried to quit smoking at least once; 24,3% within the last 12 months. Quit attempts were mostly undertaken without formal help (53,7%). Users of smoking cessation aids report that they used social support (22,6%), self-help material (13,3%), nicotine replacement products (11,3%) and E-cigarettes (8,4%). Conclusions: Compared to the year 2000 the number of former smokers has increased. While the number of smoking cessation attempts among smokers is unchanged, more smokers use smoking cessation aids. Using E-cigarettes for smoking cessation is becoming more important. PMID- 26158344 TI - [Vaccine Refrigerator and Vaccine Management in General Practices: A Representative, Web-Based Survey among General Practitioners (Keep Cool I)]. AB - Aim: The purpose of this study was to analyse vaccine refrigerator and vaccine management in primary care and to identify physician- and practice-related influencing factors. Background: Adequate cooling of vaccines in a temperature range of 2-8 degrees C is essential to assure vaccine effectiveness. Studies from various countries have demonstrated cooling chain problems. We surveyed general practitioners about the quality of their vaccine refrigerator and vaccine management and aimed at identifying physician- and practice-related influencing factors. Methods: A cross-sectional, web-based questionnaire survey was performed among 3 physician populations in primary care: a 10% random sample of general practitioners (n=954), all teaching physicians of the Universities Duisburg-Essen (n=221) and Halle-Wittenberg (n=92). Surveyed were items on the following 6 aspects: (1) responsibilities within practice teams, (2) vaccine ordering and storing, (3) criteria for the vaccine pre-selection, (4) stocking system inside the refrigerator, (5) wrapping, and use of stocking boxes, (6) refrigerator and temperature control. The quality indicator "comprehensive refrigerator management" was defined to include 4 aspects: (1) separate refrigerator, (2) written temperature documentation (temperature-logbook), (3) regular storage control (wrapping, temperature and expiration date), and (4) storage in original wrappings. Results: A total of 278 physicians participated in the survey (22%). Of these, 80% had a separate refrigerator, 52% reported written temperature documentation, 93% documented regular storage control addressing vaccine wrappings, temperature and expiration dates, and 95% reported vaccine storage in original card box wrappings. A "comprehensive refrigerator management" was realised by 42% of the practices. This indicator was reached more frequently by practices with 3 or more physicians (p=0.01) and those with an additional qualification in travel medicine (p=0.036). Conclusion: Our survey showed good results for most aspects of the refrigerator and vaccine management but room for improvement with regard to temperature documentation. PMID- 26158345 TI - [Psychological Well-being of Highly-sensitive Persons in Transition to Parenthood - A Cross-sectional Study]. AB - BACKGROUND: Well-being of highly sensitive people in the transformation period to parenthood is of increasing concern. This study examines whether the transformation period to parenthood has a higher effect on the psychological well being (PWB) of highly sensitive people than on not highly sensitive people. METHOD: A cross-sectional study was undertaken of parents (n=614), highly sensitive (n=440) and not highly sensitive (n=174), at the transition to parenthood. Instruments were the Ryff psychological well-being scale. Independent variables and well-being were examined by descriptive and bivariate methods. RESULT: Well-being of highly sensitive parents is associated with transition to parenthood (b=-10,129; p<0.05) compared to the control group (7.3% of highly sensitive <50% of PWB; 0.6% of not highly sensitive <50% of PWB). CONCLUSION: As one of the first studies, this examination looks into the data of highly sensitive parents. It can be stated that there is an urgent need for research in this area. Because with a prevalence of 10-20% highly sensitive people within the population, it can be assumed that highly sensitive mostly young parents, could be an important target group of health promotion. PMID- 26158346 TI - Cloning and characterization of a novel PE_PGRS60 protein (Rv3652) of Mycobacterium tuberculosis H37 Rv exhibit fibronectin-binding property. AB - The binding of pathogenic bacteria to extracellular matrix components enhances adhesion and invasion of host cells. The host receptor proteins such as fibronectin (Fn) targeted to pathogenic ligands that have clinical importance. In the present study, we cloned, expressed, purified, and identified a novel Fn binding protein from PE_PGRS60 (Rv3652) of Mycobacterium tuberculosis H37 Rv. The protein product of Rv3652 showed optimum binding efficiency to 10 ng Fn at 0.2 ug purified protein of PE_PGRS60 and 20 ng Fn at 0.2 ug concentrations, respectively. PE_PGRS60 protein (primary sequences) of different pathogenic mycobacterium species retrieved from NCBI exhibited complete homology at the 104 residues on multiple sequence alignment. The primary sequence of protein from H37 Rv was further used to predict cleavage signals. The secondary structure prediction method revealed a number of residues responsible for alpha helices formation and percentage of residues participating in the random coils and extended strands. In addition, online prediction tools such as B- and T-cell epitopes showed the surface probability scale and antigenic propensity scale. The current finding opens new opportunity to mycobacterial survival and pathogenesis research of PE-polymorphic GC-rich repetitive sequences (PE-PGRS) family proteins. PMID- 26158347 TI - The effect of five Taraxacum species on in vitro and in vivo antioxidant and antiproliferative activity. AB - Plants belonging to the genus Taraxacum are considered a nutritious food, being consumed raw or cooked. Additionally, these plants have long been used in folk medicine due to their choleretic, diuretic, antitumor, antioxidant, antiinflammatory, and hepatoprotective properties. This genus, with its complex taxonomy, includes several species that are difficult to distinguish. Its traditional use must be related not only to T. officinale F.H. Wigg., the most studied species, but also to others. The aim of this work is to compare five different common South European species of Taraxacum (T. obovatum (Willd.) DC., T. marginellum H. Lindb., T. hispanicum H. Lindb., T. lambinonii Soest and T. lacistrum Sahlin), in order to find differences between antioxidant and cytotoxic activities among them. Dissimilarities between species in LC/MS patterns, in in vitro and intracellular antioxidant activity and also in the cytotoxicity assay were found. T. marginellum was the most efficient extract reducing intracellular ROS levels although in in vitro assays, T. obovatum was the best free radical scavenger. A relevant cytotoxic effect was found in T. lacistrum extract over HeLa and HepG2 cell lines. PMID- 26158348 TI - Converting between the oxides of nitrogen using metal-ligand coordination complexes. AB - The oxides of nitrogen (chiefly NO, NO3(-), NO2(-) and N2O) are key components of the natural nitrogen cycle and are intermediates in a range of processes of enormous biological, environmental and industrial importance. Nature has evolved numerous enzymes which handle the conversion of these oxides to/from other small nitrogen-containing species and there also exist a number of heterogeneous catalysts that can mediate similar reactions. In the chemical space between these two extremes exist metal-ligand coordination complexes that are easier to interrogate than heterogeneous systems and simpler in structure than enzymes. In this Tutorial Review, we will examine catalysts for the inter-conversions of the various nitrogen oxides that are based on such complexes, looking in particular at more recent examples that take inspiration from the natural systems. PMID- 26158349 TI - Palladium-catalyzed direct C-H arylations of dioxythiophenes bearing reactive functional groups: a step-economical approach for functional pi-conjugated oligoarenes. AB - A Pd-catalyzed single-step C-H arylation of dioxythiophene derivatives bearing unprotected reactive functional groups (-OH, -COOH, -N3) in a phosphine-free manner has been developed. Various dioxythiopene-based oligoarenes with extended pi-conjugation are obtained with good yields (up to 90%). These oligoarenes display suitable optical properties (absorption and emission maxima, quantum yields) and contain reactive functional groups suitable for further conjugations with bioactive molecules. This new methodology is step economical (fewer synthetic steps) and environmentally friendly (no toxic metal-containing by products) and the oligoarenes synthesized are potentially applicable for bio labeling, bioimaging, and biosensing. PMID- 26158351 TI - Adults Meeting Fruit and Vegetable Intake Recommendations - United States, 2013. AB - Eating more fruits and vegetables adds nutrients to diets, reduces the risk for heart disease, stroke, and some cancers, and helps manage body weight when consumed in place of more energy-dense foods. Adults who engage in <30 minutes of moderate physical activity daily should consume 1.5-2.0 cup equivalents of fruit and 2-3 cups of vegetables daily.* However, during 2007-2010, half of the total U.S. population consumed <1 cup of fruit and <1.5 cups of vegetables daily; 76% did not meet fruit intake recommendations, and 87% did not meet vegetable intake recommendations. Although national estimates indicate low fruit and vegetable consumption, substantial variation by state has been observed (3). Fruit and vegetable intake information from the Behavioral Risk Factor Surveillance System (BRFSS) is the sole source of dietary surveillance information for most states, but frequency of intake captured by BRFSS is not directly comparable to federal intake recommendations, which are expressed in cup equivalents. CDC analyzed median daily frequency of fruit and vegetable intake based on 2013 BRFSS data for the 50 states and the District of Columbia (DC) and applied newly developed prediction equations to BRFSS to calculate the percentage of each state's population meeting fruit and vegetable intake recommendations. Overall, 13.1% of respondents met fruit intake recommendations, ranging from 7.5% in Tennessee to 17.7% in California, and 8.9% met vegetable recommendations, ranging from 5.5% in Mississippi to 13.0% in California. Substantial new efforts are needed to build consumer demand for fruits and vegetables through competitive pricing, placement, and promotion in child care, schools, grocery stores, communities, and worksites. PMID- 26158350 TI - SERPINA1 is a direct estrogen receptor target gene and a predictor of survival in breast cancer patients. AB - Of all breast cancer patients, about 70% are ER+ and 10% are ER+/HER2+. The ER+/HER2+ patients have a worse outcome compared to ER+/HER2- patients. Currently there is a lack of effective prognosis biomarkers for the prediction of outcome in ER+/HER2+ patients. Genome-wide differences in ER binding between the endocrine-responsive and endocrine-resistant cells were discovered using ChIP seq, and combined with gene expression microarray data to identify direct ER target genes. These genes were correlated to survival outcome using publicly available breast cancer patient cohorts. We found the expression of the gene SERPINA1 to have a significant predictive value for the overall survival (OS) of ER+ patients in the TCGA cohort, and validated this finding in the Curtis cohort. SERPINA1 also has a significant predictive value for the OS of ER+/HER2+ patients in the TCGA cohort, with validation in the Bild cohort. The expression of SERPINA1 can be suppressed by fulvestrant and HER2 siRNA. Our results indicate that ER is constitutively activated, resulting in an E2-independent ER binding to the SERPINA1 gene and upregulation of SERPINA1 expression. Importantly, results of survival correlation suggests that high expression of SERPINA1 could be predictive for a better clinical outcome of ER+ and ER+/HER2+ patients. PMID- 26158352 TI - Community Knowledge, Attitudes, and Practices Regarding Ebola Virus Disease - Five Counties, Liberia, September-October, 2014. AB - As of July 1, 2015, Guinea, Liberia, and Sierra Leone have reported a total of 27,443 confirmed, probable, and suspected Ebola virus disease (Ebola) cases and 11,220 deaths. Guinea and Sierra Leone have yet to interrupt transmission of Ebola virus. In January, 2016, Liberia successfully achieved Ebola transmission free status, with no new Ebola cases occurring during a 42-day period; however, new Ebola cases were reported beginning June 29, 2015. Local cultural practices and beliefs have posed challenges to disease control, and therefore, targeted, timely health messages are needed to address practices and misperceptions that might hinder efforts to stop the spread of Ebola. As early as September 2014, Ebola spread to most counties in Liberia. To assess Ebola-related knowledge, attitudes, and practices (KAP) in the community, CDC epidemiologists who were deployed to the counties (field team), carried out a survey conducted by local trained interviewers. The survey was conducted in September and October 2014 in five counties in Liberia with varying cumulative incidence of Ebola cases. Survey results indicated several findings. First, basic awareness of Ebola was high across all surveyed populations (median correct responses = 16 of 17 questions on knowledge of Ebola transmission; range = 2-17). Second, knowledge and understanding of Ebola symptoms were incomplete (e.g., 61% of respondents said they would know if they had Ebola symptoms). Finally, certain fears about the disease were present: >90% of respondents indicated a fear of Ebola patients, >40% a fear of cured patients, and >50% a fear of treatment units (expressions of this last fear were greater in counties with lower Ebola incidence). This survey, which was conducted at a time when case counts were rapidly increasing in Liberia, indicated limited knowledge of Ebola symptoms and widespread fear of Ebola treatment units despite awareness of communication messages. Continued efforts are needed to address cultural practices and beliefs to interrupt Ebola transmission. PMID- 26158353 TI - Vital Signs: Demographic and Substance Use Trends Among Heroin Users - United States, 2002-2013. AB - BACKGROUND: Heroin use and overdose deaths have increased significantly in the United States. Assessing trends in heroin use among demographic and particular substance-using groups can inform prevention efforts. METHODS: FDA and CDC analyzed data from the National Survey on Drug Use and Health and National Vital Statistics System reported during 2002-2013. Trends in heroin use among demographic and substance using groups were compared for 2002-2004, 2005-2007, 2008-2010, and 2011-2013. A multivariable logistic regression model was used to identify characteristics associated with heroin abuse or dependence. RESULTS: Annual average rates of past-year heroin use increased from 1.6 per 1,000 persons aged >= 12 years in 2002-2004 to 2.6 per 1,000 in 2011-2013. Rates of heroin abuse or dependence were strongly positively correlated with rates of heroin related overdose deaths over time. For the combined data years 2011-2013, the odds of past-year heroin abuse or dependence were highest among those with past year cocaine or opioid pain reliever abuse or dependence. CONCLUSIONS: Heroin use has increased significantly across most demographic groups. The increase in heroin abuse or dependence parallels the increase in heroin-related overdose deaths. Heroin use is occurring in the context of broader poly-substance use. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Further implementation of a comprehensive response that targets the wider range of demographic groups using heroin and addresses the key risk factors for heroin abuse and dependence is needed. Specific response needs include reducing inappropriate prescribing and use of opioids through early identification of persons demonstrating problematic use, stronger prescription drug monitoring programs, and other clinical measures; improving access to, and insurance coverage for, evidence-based substance abuse treatment, including medication-assisted treatment for opioid use disorders; and expanding overdose recognition and response training and access to naloxone to treat opioid pain reliever and heroin overdoses. PMID- 26158354 TI - Manipulating the Excited States of Cyclometalated Iridium Complexes with beta Ketoiminate and beta-Diketiminate Ligands. AB - A series of cyclometalated iridium complexes with beta-ketoiminate and beta diketiminate ligands are described. Two different cyclometalating (C^N) ligands-2 phenylpridine (ppy) and 2-phenylbenzothiazole (bt)-are used in concert with three different ancillary (LX) ligands-a phenyl-substituted beta-ketoiminate (acNac(Me)), a phenyl-substituted beta-diketiminate (NacNac(Me)), and a fluorinated version of the beta-diketiminate (NacNac(CF3))-to furnish a suite of six complexes. The complexes are prepared by metathesis reactions of chloro bridged dimers [Ir(C^N)2(MU-Cl)]2 with potassium or lithium salts of the ancillary LX ligand. Four of the complexes are characterized by X-ray crystallography, and all six were subjected to in-depth optical and electrochemical interrogation. Cyclic voltammetry shows both reduction and oxidation waves, with the latter strongly dependent on the identity of the LX ligand. The complexes are all luminescent, with the nature of the emissive excited state and the quantum yield (Phi) dependent on the identity of both the C^N and LX ligands. Whereas the complexes Ir(ppy)2(NacNac(Me)) and Ir(ppy)2(acNac(Me)) are weakly luminescent (Phi ~ 0.01), the complexes Ir(bt)2(NacNac(Me)) and Ir(bt)2(acNac(Me)) are strongly luminescent, with the latter's quantum efficiency (Phi = 0.82) among the highest ever observed for cyclometalated iridium complexes. Fluorination of the NacNac ligand gives rise to completely disparate emission behavior suggestive of a NacNac-centered emissive state. The results described here, in comparison with previous groups' studies on acetylacetonate (acac) analogues, suggest that the weaker-field NacNac and acNac ligands raise the energy of the metal-centered HOMO, with energy of the HOMO increasing in the order NacNac(CF3) < acNac(Me) < NacNac(Me). PMID- 26158355 TI - Non-tuberculous mycobacterium skin infections after tattooing in healthy individuals: A systematic review of case reports. AB - In recent years, several case reports and outbreaks reported occurrence of non tuberculous mycobacteria (NTM) infections within 6 months after receiving a tattoo in healthy individuals. NTM species (e.g., Chelonae, Fortuitum, Hemophillum, and Abscessus) are widespread in the environment and it is often suspected that contamination may occur through unsterile instrumentation or unsterile water used for diluting tattoo ink to dilute color. In reported cases, lesions were mainly restricted to a single color 'gray' part of the tattoo. Mycobacterium Chelonae was the most common cause of tattoo associated NTM infections. Less than 50% of the case reports tested tattoo ink for acid fast bacilli stains and cultures. Subjects required treatment with either clarithromycin alone or in combination with quinolones for 6 to 9 months. An increase in NTM skin infections in healthy individuals after tattooing indicates the need for sterile standards during tattooing and improved local and regional regulatory oversight. PMID- 26158356 TI - The association of the sebum excretion rate with melasma, erythematotelangiectatic rosacea, and rhytides. AB - BACKGROUND: Rosacea and melasma are two common skin conditions in dermatology. Both conditions have a predilection for the centrofacial region where the sebaceous gland density is the highest. However it is not known if sebaceous function has an association with these conditions. AIMS AND OBJECTIVES: We aimed to assess the relationship between facial glabellar wrinkle severity and facial sebum excretion rate for individuals with rosacea, melasma, both conditions, and in those with rhytides. Secondly, the purpose of this study was to utilize high resolution 3D facial modeling and measurement technology to obtain information regarding glabellar rhytid count and severity. MATERIALS AND METHODS: A total of 21 subjects participated in the study. Subjects were divided into four groups based on facial features: rosacea-only, melasma-only, rosacea and melasma, rhytides-only. A high resolution facial photograph was taken followed by measurement of facial sebum excretion rate (SER). RESULTS: The SER was found to decline with age and with the presence of melasma. The SER negatively correlated with increasing Wrinkle Severity Rating Scale. Through the use of 3D facial modeling and skin analysis technology, we found a positive correlation between clinically based grading scores and computer generated glabellar rhytid count and severity. CONCLUSION: Continuing research with facial modeling and measurement systems will allow for development of more objective facial assessments. Future studies need to assess the role of technology in stratifying the severity and subtypes of rosacea and melasma. Furthermore, the role of sebaceous regulation may have important implications in photoaging. PMID- 26158357 TI - How to reduce out-of-pocket costs for prescription medications. AB - The cost of prescription medicines has recently been rising faster than other healthcare costs. This is also true for traditionally inexpensive generic medications that have long served as a fundamental healthcare safety net in the USA. These changes increasingly present challenges for individuals to obtain common medications. Owing to rising insurance co-pays, even patients who have prescription medication insurance coverage are beginning to experience challenges in this area. This document was created to help patients and their families consider various strategies and programs that exist in 2015 for reducing their out-of-pocket costs for their prescription medications. We believe that this information can also be helpful to healthcare providers when counseling patients about managing rapidly rising prescription drug costs. An effort has been made to make this document readable to patients and their families as well as to healthcare providers. PMID- 26158358 TI - Defining intrinsic vs. extrinsic atopic dermatitis. AB - Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by eczematous lesions, i.e. ill-demarcated erythematous patches and plaques. AD is commonly associated with elevated immunoglobulin E (IgE) and atopic disorders, such as asthma, hay fever, and food allergies. Rackemann and Mallory were some of the first to distinguish between asthma based on the presence ("extrinsic") or absence ("intrinsic") of allergy. This distinction has subsequently been applied to AD based on the presence ("extrinsic") or absence ("intrinsic") of increased IgE and atopic disease. Although the distinction between intrinsic and extrinsic AD is widely used, it remains controversial. PMID- 26158359 TI - Understanding the logic of common suturing techniques in dermatologic surgery. AB - Although most trainees in dermatology learn that different suturing techniques are designated for a specific purpose (i.e., certain functional and cosmetic outcomes), students often have a difficult time visualizing how a given suture functions in its designated capacity. In this article, we address the logic behind the most common suturing techniques in dermatologic surgery, including the direction and magnitude of their pulling force with respect to the wound edges and the ensuing displacement of dermal and epidermal structures. To aid better understanding, we diagram the vectors of suture force with each of the techniques discussed. PMID- 26158360 TI - Sclerodermoid lesions in a patient with multiple transplants and porphyria cutanea tarda. AB - Patients with chronic graft versus host disease may exhibit a range of sclerotic features. Herein we present a patient with confirmed porphyria cutanea tarda who subsequently developed chronic graft versus host disease. PMID- 26158361 TI - Pink plaque on the arm of a man after a trip to Mexico: cutaneous leishmaniasis. AB - Cutaneous leishmaniasis is a parasitic infection caused by protozoa of the Leishmania genus that presents as asymptomatic pink papules that may ulcerate. There are several species of Leishmania found in 98 endemic countries and whereas all are associated with cutaneous disease, only specific species can cause mucocutaneous or visceral disease. Although the diagnosis of cutaneous leishmaniasis can be confirmed with Giemsa staining of a biopsy or "touch prep" specimen, only speciation at specialized centers such as the Centers for Disease Control (CDC) can determine the risk of mucocutaneous or visceral disease. Treatment of cutaneous leishmaniasis is varied and depends on the extent of cutaneous disease and the risk of mucocutaneous or visceral disease. PMID- 26158362 TI - Tender, necrotic plaques of the glans penis due to calciphylaxis. AB - Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare, but often fatal condition involving vascular calcification that can result in tissue ischemia and cutaneous necrosis. It is most often seen in patients with renal failure among many other occasionally reported etiologies. Below, we present a rare and challenging case of calciphylaxis involving the glans penis and right leg in a man with end stage renal disease on hemodialysis. PMID- 26158363 TI - Repigmentation of hair following adalimumab therapy. AB - Repigmentation of canities, or age-related grey or white hair, is a rare occurrence. Generalized repigmentation of grey-white hair has been reported following inflammatory processes, and heterochromia (localized patches of hair repigmentation) is even more unusual, reported in association with medication use and malignancy. Tumor necrosis factor (TNF) inhibitors are increasingly utilized medications for inflammatory disorders, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Hair loss, or alopecia, has been described among the side effects of these medications, but changes in hair pigmentation in association with this class of drugs have not previously been reported. We describe a patient with hair repigmentation associated with adalimumab therapy. PMID- 26158364 TI - A case of self-healing juvenile cutaneous mucinosis. AB - IMPORTANCE: Self-healing juvenile cutaneous mucinosis is a very rare, self limiting disease characterized by the abrupt onset of asymptomatic papules and nodules located primarily on the face and periarticular regions of a juvenile patient. There have been less than 20 cases reported since it was first described in 1973. OBSERVATIONS: Most cases have been reported in children 15 years and younger. Herein we present a case affecting a 17-year-old. To our knowledge, this the oldest reported patient with this condition in the USA. CONCLUSIONS AND RELEVANCE: Despite the rarity of this disease, it is important to keep SHJCM on the differential in pediatric patients presenting with proliferating papules and nodules. Knowledge of this entity may prevent unnecessary diagnostic testing and aggressive treatment in the pediatric population with this self-limited disease. PMID- 26158365 TI - Post-radiation atypical vascular proliferation on the head of a young woman: a diagnostic challenge. AB - With improved outcomes associated with radiotherapy (RT), post-irradiation tumors are increasingly seen in long-term cancer survivors. We report a case of a young woman who presented with a three-year history of a vascular lesion on the temple, previously irradiated for a childhood brain tumor. The history of radiation, the clinical appearance, and the biopsy findings of an atypical vascular proliferation in the dermis, were worrisome for a malignant vascular neoplasm and prompted surgical excision. However, further tissue analysis of the excised specimen confirmed a benign atypical vascular lesion (AVL) overlying a banal pilar cyst. Distinguishing post-radiation benign from malignant vascular lesions can be difficult because they share overlapping clinical and histopathologic features. Thus, any vascular lesion that occurs in a previously irradiated field should be excised completely with tumor-free margins and examined histologically. PMID- 26158366 TI - A case of Graham-Little-Piccardi-Lasseur syndrome. AB - Graham-Little-Piccardi-Lasseur Syndrome (GLPLS) is a variant of lichen planopilaris, which is characterized by progressive cicatricial alopecia of scalp, non-cicatricial alopecia of axillae and pubic regions, and keratosis pilaris-like follicular papules over trunk and extremities. GLPLS is a disease of unknown etiology. However, recent reports support a central role for a T-cell mediated immune response in the pathogenesis of GLPLS. Besides, although GLPLS is believed to occur sporadically, a genetic predisposition also has been implicated in the pathogenesis. On the other hand, GLPLS typically affects middle-aged women, particularly of the postmenopausal age group. A diagnosis of GLPLS is generally apparent with the presence of characteristic findings in a postmenopausal woman. Herein, we report a case of GLPLS in a 75-year-old woman with the typical triad of alopecia of the scalp, non-cicatricial alopecia of axillae and pubis, and a follicular keratotic eruption on the trunk. PMID- 26158367 TI - Aquagenic palmar wrinkling in two Indian patients with special reference to its dermoscopic pattern. AB - Aquagenic palmar wrinkling (APW), synonymously known as aquagenic syringeal acrokeratoderma, transient aquagenic palmar hyperwrinkling, aquagenic palmoplantar keratoderma, or transient reactive papulotranslucent acrokeratoderma, is a distinctive dermatosis characterized by whitish papules, excessive wrinkling, and possible desquamation of the palms and/or soles after immersion into water for a short time. We describe herein two cases of aquagenic palmar wrinkling in Indian patients with special reference to its dermoscopic pattern. Since its initial description, only a few cases of APW have been described in literature. To the best of our knowledge, APW is a hitherto unreported condition in Indian population. PMID- 26158368 TI - Embedded tooth fragment masquerading as keloid for 11 months. AB - A foreign body retained in the skin can originate from numerous sources and most of the time these foreign bodies are removed without any sequelae. The present article reports a case of persistent swelling in the lower lip misdiagnosed as keloid, which later turned out to be an embedded tooth fragment identified post spontaneous extrusion after 11 months. PMID- 26158369 TI - Red-white and blue baby: a case of phacomatosis pigmentovascularis type V. AB - Phacomatosis pigmentovascularis is a rare genodermatosis characterized by the combination of an extensive pigmentary nevus with a widespread vascular nevus. The coexistence of aberrant dermal melanocytosis and cutis marmorata telangiectatica congenita has been termed phacomatosis pigmentovascularis type V or phacomatosis cesiomarmorata. Phacomatosis pigmentovascularis type V was first described in a 3-month-old boy in 2000. Since then, there have been a further seven cases published in the literature. PMID- 26158370 TI - Apremilast and adalimumab: a novel combination therapy for recalcitrant psoriasis. AB - Psoriasis is a chronic immune-mediated inflammatory condition that affects 2-3% of the population. Apremilast was FDA-approved in March 2014 for the treatment of psoriatic arthritis and in September 2014 for the treatment of moderate to severe plaque psoriasis. Apremilast appears to have lower efficacy than some biologic agents such as adalimumab and ustekinumab, which achieve a PASI-75 in approximately 70% of patients after 12-16 weeks of therapy. However, its ease of administration as an oral agent coupled with a mild side effect profile make it an attractive option for psoriasis treatment. Herein, we present a patient with a 17-year history of plaque type psoriasis recalcitrant to topical, oral, and biologic mediations who attained near-complete remission after therapy with a combination of adalimumab and apremilast. PMID- 26158371 TI - Overcalling a teledermatology selfie: a new twist in a growing field. AB - Teledermatology via patient-generated digital images or "selfies" has been increasing since the advent of portable devices capable of high resolution image capture. During these early days, doctors and patients are learning about uses and limitations. We describe a case in which a patient's selfie led three attending physicians to suspect an iatrogenic hematoma requiring urgent assessment. There was no hematoma at follow up, simply dark and smooth adherent crust, which was gently removed to reveal a well-healing wound. This case introduces a previously undescribed teledermatology-related issue, that of "overcalling" a selfie. An image supplied by a patient misleadingly appeared to show a serious complication requiring urgent treatment. PMID- 26158372 TI - Pachydermoperiostosis and bladder cancer. AB - Pachydermoperiostosis or the Touraine-Soulente-Gole syndrome is a rare monogenetic disorder characterized by pachydermia, periostosis and digital clubbing accounts for approximately 3~5% of all patients with hypertrophic osteoarthropathy. Missense mutations in SLCO2A1 and HPGD genes could plausibly underlie the pathogenesis of pachydermoperiostosis. Patients have usually a favorable outcome with very few cases associated with cancer. Herein, we report the first case of a patient with pachydermoperiostosis associated with bladder cancer. PMID- 26158373 TI - Melanoma in situ or superficial basal cell carcinoma? AB - Dermoscopy is a non-invasive, in vivo technique that increases accuracy in the diagnosis of both melanocytic and non-melanocytic skin tumors. A 74-year-old woman presented with a 3-year history of a slow-growing, asymptomatic, slightly pigmented plaque on the back. The dermoscopic differential diagnosis of melanoma in situ versus superficial basal cell carcinoma is discussed, based on the presentation of peripheral brown irregular finger-like projections. These were also associated with peripheral fine short telangiectasias, shiny white to red structureless areas, a few brown globules, and small erosions. Histopathological examination confirmed the diagnosis of superficial pigmented basal cell carcinoma. A brief review of the dermoscopic structures associated with this common nonmelanocytic skin tumor is also made. PMID- 26158374 TI - Guided self-help for generalized anxiety disorder in older adults. AB - OBJECTIVE: The main objective of this study was to examine the efficacy of a guided self-help treatment based on cognitive behavioral principles (CBT-GSH) for generalized anxiety disorder (GAD) in older adults. METHODS: Three older adults aged from 66 to 70 and diagnosed with GAD were included in a single-case experimental multiple-baseline protocol. Data were collected using daily self monitoring, standardized clinician ratings, and self-report questionnaires at pretest, posttest, and 6-month and 12-month follow-ups. Treatment consisted of awareness training, worry interventions, relaxation training, pleasant activities scheduling, and relapse prevention. Participants used a manual presenting weekly readings and at-home practice exercises. They also received weekly supportive phone calls from a therapist. RESULTS: At posttest, participants showed improvement on worries and GAD severity, on psychological process variables targeted by treatment (intolerance of uncertainty, negative problem orientation, cognitive avoidance, and perceived usefulness of worry), and on secondary variables associated with GAD (anxiety, depression, sleep difficulties, cognitive functioning, and disability). These results were generally maintained at 12 months after the end of treatment. Participants had favorable opinions toward the treatment. CONCLUSION: The results of this study suggest that CBT-GSH is both feasible and effective for the treatment of GAD in older adults. PMID- 26158375 TI - Nickel Hydroxide-Modified Sulfur/Carbon Composite as a High-Performance Cathode Material for Lithium Sulfur Battery. AB - Tailored sulfur cathode is vital for the development of a high performance lithium-sulfur (Li-S) battery. A surface modification on the sulfur/carbon composite would be an efficient strategy to enhance the cycling stability. Herein, we report a nickel hydroxide-modified sulfur/conductive carbon black composite (Ni(OH)2@S/CCB) as the cathode material for the Li-S battery through the thermal treatment and chemical precipitation method. In this composite, the sublimed sulfur is stored in the CCB, followed by a surface modification of Ni(OH)2 nanoparticles with size of 1-2 nm. As a cathode for the Li-S battery, the as-prepared Ni(OH)2@S/CCB electrode exhibits better cycle stability and higher rate discharge capacity, compared with the bare S/CCB electrode. The improved performance is largely due to the introduction of Ni(OH)2 surface modification, which can effectively suppress the "shuttle effect" of polysulfides, resulting in enhanced cycling life and higher capacity. PMID- 26158378 TI - Polyurethane Dispersions with Peptide Corona: Facile Synthesis of Stimuli Responsive Dispersions and Films. AB - Peptide-polymer hybrid particles of submicron size yielding stimuli-responsive macroscopic films are presented. A thermoplastic polyurethane (PU) carrying polysiloxane and polyester soft segments serves as core material to obtain flexible, yet semicrystalline films with temperature-sensitivity. The synthesis is based on the high-sheer emulsification of isocyanate-terminated PU prepolymers, which in our model system purposefully lack any ability of colloidal self-stabilization. While emulsification in water leads to immediate coagulation, stable dispersions of polyurethane nanoparticles were formed in aqueous solutions of a hydrolyzed protein from wool. A comparison of dispersion and film properties to nonreactive, otherwise identical dispersions suggests covalent attachment of the peptide to the PU backbone. We show that the colloidal stability of the hybrid particles is completely governed by the peptide corona, and hence pH triggered coagulation can be employed to induce particle deposition and film formation. Differential scanning calorimetry confirms partial crystallinity in the film and reveals strongly modified crystallization behavior due to the peptide. PMID- 26158380 TI - Capillary Force between Flexible Filaments. AB - Liquid droplets bridging filaments are ubiquitous in nature and technology. Although the liquid-surface shape and the capillary force and torque have been studied extensively, the effect of filament flexibility is poorly understood. Here, we show that elastic deformation (at large values of the elasto-capillary number) can significantly affect the liquid-surface shape and capillary force. The equilibrium state of parallel filaments is calculated using analytical approximations and numerical solutions for the fluid interface. The results compare well, and the numerical solution is then applied to crossing filaments. In the investigated range of parameters, the capillary force increases rapidly when the filaments touch. The force decreases continuously when decreasing the liquid volume for parallel hydrophilic filaments but produces a maximum for crossed filaments. The liquid volume at the maximum force is reported when changing the filament flexibility, crossing angle, and contact angle. These results may be beneficial in applications where the strength and structure of wet fibrous materials are important, such as in paper formation and when welding flexible components. PMID- 26158379 TI - Alternative polyadenylation coupled to transcription initiation: Insights from ELAV-mediated 3' UTR extension. AB - Transcription initiation and mRNA maturation were long considered co-occurring but separately regulated events of gene control. In the past decade, gene promoters, the platforms of transcription initiation, have been assigned additional functions such as the regulation of splicing and 3' end processing. In a recent study, Oktaba and Zhang and al. reveal that neural 3' UTR extension is dependent on promoter sequences. In Drosophila neurons, promoter regions of a subset of genes recruit the RNA-binding protein ELAV, which is required for subsequent ELAV-mediated alternative polyadenylation. Intriguingly, RNA Polymerase II pausing at promoters seems to facilitate ELAV recruitment. How transcription initiation and alternative polyadenylation, processes separated by an entire gene length, are functionally linked, remains unsolved. In this article, I summarize recent findings and discuss possible mechanisms. PMID- 26158381 TI - Boards of trustees must assume responsibility for making alcohol prevention on campus a top priority. AB - Few colleges have made the prevention of alcohol-related injuries and deaths an institutional priority, and even fewer have implemented prevention strategies with a solid evidentiary base. We look to presidents to provide leadership on this issue, but those who do are atypical. Boards of trustees should step in by asserting that student wellness be a primary focus in the institution's strategic plan, with specific, measurable goals; holding the president accountable for progress in reducing high-risk drinking and its consequences; and mandating a line item in the annual budget, with adequate staffing and revenues to put evidence-based practices in place. Boards will be more likely to respond when led to focus on the cost implications of the campus alcohol problem; the link between high-risk drinking and mission-critical institutional objectives such as academic performance, student engagement, and retention; and the institution's potential liability if evidence-based prevention strategies are not in place. PMID- 26158382 TI - Identification of rice blast resistance genes in the elite hybrid rice restorer line Yahui2115. AB - Rice blast, caused by the ascomycete fungus Magnaporthe oryzae, is one of the most serious rice diseases worldwide. We previously developed an elite hybrid rice restorer line with high resistance to rice blast, Yahui2115 (YH2115). To identify the blast resistance genes in YH2115, we first performed expression profiling on previously reported blast resistance genes and disease assay on monogenic lines, and we found that Pi2, Pi9, and Pikm were the most likely resistance candidates in YH2115. Furthermore, RNA interference and linkage analysis demonstrated that silencing of Pi2 reduced the blast resistance of YH2115 and a Pi2 linkage marker was closely associated with blast resistance in an F2 population generated from YH2115. These data suggest that the broad spectrum blast resistance gene Pi2 contributes greatly to the blast resistance of YH2115. Thus, YH2115 could be used as a new germplasm to facilitate rice blast resistance breeding in hybrid rice breeding programs. PMID- 26158383 TI - Synergistic interactions of biotic and abiotic environmental stressors on gene expression. AB - Understanding the response of organisms to multiple stressors is critical for predicting if populations can adapt to rapid environmental change. Natural and anthropogenic stressors often interact, complicating general predictions. In this study, we examined the interactive and cumulative effects of two common environmental stressors, lowered calcium concentration, an anthropogenic stressor, and predator presence, a natural stressor, on the water flea Daphnia pulex. We analyzed expression changes of five genes involved in calcium homeostasis - cuticle proteins (Cutie, Icp2), calbindin (Calb), and calcium pump and channel (Serca and Ip3R) - using real-time quantitative PCR (RT-qPCR) in a full factorial experiment. We observed strong synergistic interactions between low calcium concentration and predator presence. While the Ip3R gene was not affected by the stressors, the other four genes were affected in their transcriptional levels by the combination of the stressors. Transcriptional patterns of genes that code for cuticle proteins (Cutie and Icp2) and a sarcoplasmic calcium pump (Serca) only responded to the combination of stressors, changing their relative expression levels in a synergistic response, while a calcium-binding protein (Calb) responded to low calcium stress and the combination of both stressors. The expression pattern of these genes (Cutie, Icp2, and Serca) were nonlinear, yet they were dose dependent across the calcium gradient. Multiple stressors can have complex, often unexpected effects on ecosystems. This study demonstrates that the dominant interaction for the set of tested genes appears to be synergism. We argue that gene expression patterns can be used to understand and predict the type of interaction expected when organisms are exposed simultaneously to natural and anthropogenic stressors. PMID- 26158384 TI - Tyramide-FISH mapping of single genes for development of an integrated recombination and cytogenetic map of chromosome 5 of Allium cepa. AB - Chromosome 5 of onion carries major quantitative trait loci (QTL) that control dry-matter content, pungency and storability of bulbs, amounts and types of epicuticular waxes, and resistances to abiotic factors, all of which are of interest to breeders. SNPs, SSRs, and RFLPs in expressed regions of the onion genome have been genetically mapped, and we used these clones and sequences from the NCBI database to develop DNA probes for in situ hybridization to integrate the genetic and physical maps of onion chromosome 5. We produced genomic amplicons from expressed regions of the onion genome that carried both exons and introns in order to increase the hybridization specificity of the probes and to enlarge the target DNA sizes. Tyramide-FISH technique was used to increase the detection sensitivity of relatively short target DNA regions, which range from 950 to 2100 bp. Through the integration of genetic and chromosomal maps, we were able to estimate the distribution of recombination events along onion chromosome 5. We demonstrated the efficiency of chromosomal in situ mapping of exon-intron genomic clones for the extremely large genome of onion. PMID- 26158388 TI - Biomechanical jumping differences among elite female handball players with and without previous anterior cruciate ligament reconstruction: a novel inertial sensor unit study. AB - Persistent biomechanical and jumping capacity alterations have been observed among female athletes who have sustained anterior cruciate ligament (ACL) injuries. The purpose of this study was to examine if biomechanical jumping differences persist among a cohort of elite female handball players with previous ACL reconstruction several years after return to top-level competition. In order to achieve this goal, a direct mechanics simplified analysis by using a single Inertial Sensor Unit (IU) was used. Twenty-one elite female (6 anterior cruciate ligament reconstructed and 15 uninjured control players) handball players were recruited and evaluated 6.0 +/- 3.5 years after surgical anterior cruciate ligament reconstruction. Bilateral and unilateral vertical jumps were performed to evaluate the functional performance and a single inertial sensor unit was employed in order to collect 3D acceleration and 3D orientation data. Previously ACL-reconstructed analysed athletes demonstrated significant (p < 0.05) alterations in relation to the three-dimensional axis (X-Y-Z) supported accelerations and differing jump phase durations, including jumping performance values, in both bilateral and unilateral jumping manoeuvres several years after ACL reconstruction. Identification of the encountered deficits through the use of an IU devise could provide clinicians with a new reliable tool for movement analysis in a clinical setting. PMID- 26158389 TI - Tracking the Fate of Particle Associated Fukushima Daiichi Cesium in the Ocean off Japan. AB - A three year time-series of particle fluxes is presented from sediment traps deployed at 500 and 1000 m at a site 115 km southeast of Fukushima Daiichi Nuclear Power Plant (FDNPP). Results show a high fraction of lithogenic material and mass flux peaks that do not align between the trap depths, suggesting a lateral source of sediments. Fukushima cesium-137 and cesium-134 were enhanced in flux peaks that, given variations in trap (137)Cs/(210)Pbex ratios, are characteristic of material derived from shelf and slope sediments found from <120 to >500 m. These lateral flux peaks are possibly triggered by passing typhoons. The Cs fluxes are an order of magnitude higher than were previously reported for the trap located 100 km due east of FDNPP. We attribute this large difference to the position of our trap under the southeasterly currents that carry contaminated waters and resuspended sediments away from FDNPP and into the Pacific. These higher Cs sedimentary fluxes offshore are still small relative to the inventory of Cs currently buried nearshore. Consequently, we do not expect them to effect any rapid decrease in Cs levels for the coastal sediments near FDNPP that have been linked to enhanced Cs in demersal fish. PMID- 26158390 TI - Efficient Synthesis of 3,3'-Mixed Bisindoles via Lewis Acid Catalyzed Reaction of Spiro-epoxyoxindoles and Indoles. AB - An efficient strategy for the synthesis of 3-(3-indolyl)-oxindole-3-methanol has been developed to achieve a Lewis acid catalyzed, highly regioselective ring opening of spiro-epoxyoxindoles with indoles. The method is used for the gram scale formal total synthesis of (+/-)-gliocladin C. PMID- 26158391 TI - Effects of Temperature, Oxygen Level, Ionic Strength, and pH on the Reaction of Benzene with Hydroxyl Radicals at the Air-Water Interface in Comparison to the Bulk Aqueous Phase. AB - Atmospheric aerosols (e.g., fog droplets) are complex, multiphase mediums. Depending on location, time of day, and/or air mass source, there can be considerable variability within these droplets, relating to temperature, pH, and ionic strength. Due to the droplets' inherently small size, the reactions that occur within these droplets are determined by bulk aqueous phase and air-water interfacial conditions. In this study, the reaction of benzene and hydroxyl radicals is examined kinetically in a thin-film flow-tube reactor. By varying the aqueous volume (e.g., film thickness) along the length of the reactor, both bulk and interfacial reaction rates are measured from a single system. Temperature, pH, and ionic strength are varied to model conditions typical of fog events. Oxygen-poor conditions are measured to study oxygen's overall effect on the reaction pathway. Initial rate activation energies and the bulk aqueous phase and interfacial contributions to the overall rate constant are also obtained. PMID- 26158392 TI - Two new glycosides isolated from Sapindus mukorossi fruits: effects on cell apoptosis and caspase-3 activation in human lung carcinoma cells. AB - Two new glycosides (1, 2) and two saponins (3, 4) were isolated from the fruits of Sapindus mukorossi Gaertn. The two glycosides were designated as sapindoside G (1) and 4'',4'''''-O-diacetylmukurozioside IIa (2). All four compounds exhibited inhibitory effects against A549 human lung adenocarcinoma cells with inhibition rates up to 69.2-83.3% at a concentration of 100 MUg/mL. Flow cytometric analysis revealed that compounds 1-4 could suppress A549 cell growth by promoting cell apoptosis, which was related to the activation of caspase-3. PMID- 26158393 TI - Therapists Working With Trauma Victims: The Contribution of Personal, Environmental, and Professional-Organizational Resources to Secondary Traumatization. AB - This study examined the contribution of personal variables and resources (age, mastery, tolerance for ambiguity, and stressors), environmental resources (support from family and friends, colleague support), and professional organizational resources (size of caseload with trauma victims, organizational commitment) to secondary traumatization. The sample consisted of 217 social workers employed at social service departments in Israel who worked with families in situations of distress and crisis and with adolescent girls at risk. The findings indicated that tolerance for ambiguity contributed most significantly to explaining the variance in secondary traumatization, followed by stressors. The size of the social workers' caseload with trauma victims also contributed significantly to explaining the variance in secondary traumatization. In addition, an interaction was found between age and continuance commitment. Among younger social workers, a negative association was found between continuance commitment to the organization and secondary traumatization, whereas among older social workers the association was positive. However, the contribution of the other research variables (mastery, support from family and friends, and colleague support) to explaining the variance in secondary traumatization was not statistically significant. The findings highlight the important role of personal resources and professional-organizational resources in enabling therapists to cope with the negative implications of working with trauma victims. PMID- 26158394 TI - Comparing Wild American Grapes with Vitis vinifera: A Metabolomics Study of Grape Composition. AB - We analyzed via untargeted UHPLC-ESI-Q-TOF-MS the metabolome of the berry tissues (skin, pulp, seeds) of some American Vitis species (Vitis cinerea, Vitis californica, Vitis arizonica), together with four interspecific hybrids, and seven Vitis vinifera cultivars, aiming to find differences in the metabolomes of the American Vitis sp. versus Vitis vinifera. Apart from the known differences, that is, more complex content of anthocyanins and stilbenoids in the American grapes, we observed higher procyanidin accumulation (tens to hundreds of times) in the vinifera skin and seeds in comparison to American berries, and we confirmed this result via phloroglucinolysis. In the American grapes considered, we did not detect the accumulation of pleasing aroma precursors (terpenoids, glycosides), whereas they are common in vinifera grapes. We also found accumulation of hydrolyzable tannins and their precursors in the skin of the wild American grapes, which has never been reported earlier in any of the species under investigation. Such information is needed to improve the design of new breeding programs, lowering the risk of retaining undesirable characteristics in the chemical phenotype of the offspring. PMID- 26158396 TI - Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation. AB - Ninety percent of glucose filtered by the glomerulus is reabsorbed by a sodium glucose cotransporter 2 (SGLT2), which is mainly expressed on S1 and S2 segment of renal proximal tubules. Since SGLT-2-mediated glucose reabsorption is increased under diabetic conditions, selective inhibition of SGLT2 is a potential therapeutic target for the treatment of diabetes. We have recently shown that an inhibitor of SGLT2 has anti-inflammatory and antifibrotic effects on experimental diabetic nephropathy partly by suppressing advanced glycation end products formation and oxidative stress generation in the kidney. However, the direct effects of SGLT2 inhibitor on tubular cell damage remain unclear. In this study, we investigated the effects of tofogliflozin, a highly selective inhibitor of SGLT2 on oxidative stress generation, inflammatory and proapoptotic reactions in cultured human proximal tubular cells exposed to high glucose. Tofogliflozin dose dependently suppressed glucose entry into tubular cells. High glucose exposure (30 mM) for 4 and 24 h significantly increased oxidative stress generation in tubular cells, which were suppressed by the treatment of tofogliflozin or an antioxidant N-acetylcysteine (NAC). Monocyte chemoattractant protein-1 (MCP-1) gene expression and apoptotic cell death were induced by 4 h- and 8 day-exposure to high glucose, respectively, both of which were also blocked by tofogliflozin or NAC. The present study suggests that SGLT2-mediated glucose entry into tubular cells could stimulate oxidative stress and evoke inflammatory and proapoptotic reactions in this cell type. Blockade of glucose reabsorption in tubular cells by SGLT2 inhibitor might exert beneficial effects on tubulointerstitial damage in diabetic nephropathy. PMID- 26158397 TI - The Essential Role of Circulating Thyroglobulin in Maintaining Dominance of Natural Regulatory T Cell Function to Prevent Autoimmune Thyroiditis. AB - Several key findings from the late 1960s to mid-1970s regarding thyroid hormone metabolism and circulating thyroglobulin composition converged with studies pertaining to the role of T lymphocytes in autoimmune thyroiditis. These studies cemented the foundation for subsequent investigations into the existence and antigenic specificity of thymus-derived natural regulatory T cells (nTregs). These nTregs prevented the development of autoimmune thyroiditis, despite the ever-present genetic predisposition, autoantigen (thyroglobulin), and thyroglobulin-reactive T cells. Guided by the hypothalamus-pituitary-thyroid axis as a fixed set-point regulator in thyroid hormone metabolism, we used a murine model and compared at key junctures the capacity of circulating thyroglobulin level (raised by thyroid-stimulating hormone or exogenous thyroglobulin administration) to strengthen self-tolerance and resist autoimmune thyroiditis. The findings clearly demonstrated an essential role for raised circulating thyroglobulin levels in maintaining the dominance of nTreg function and inhibiting thyroid autoimmunity. Subsequent identification of thyroglobulin specific nTregs as CD4(+)CD25(+)Foxp3(+) in the early 2000s enabled the examination of probable mechanisms of nTreg function. We observed that whenever nTreg function was perturbed by immunotherapeutic measures, opportunistic autoimmune disorders invariably surfaced. This review highlights the step-wise progression of applying insights from endocrinologic and immunologic studies to advance our understanding of the clonal balance between natural regulatory and autoreactive T cells. Moreover, we focus on how tilting the balance in favor of maintaining peripheral tolerance could be achieved. Thus, murine autoimmune thyroiditis has served as a unique model capable of closely simulating natural physiologic conditions. PMID- 26158395 TI - Predictive and comparative analysis of Ebolavirus proteins. AB - Ebolavirus is the pathogen for Ebola Hemorrhagic Fever (EHF). This disease exhibits a high fatality rate and has recently reached a historically epidemic proportion in West Africa. Out of the 5 known Ebolavirus species, only Reston ebolavirus has lost human pathogenicity, while retaining the ability to cause EHF in long-tailed macaque. Significant efforts have been spent to determine the three-dimensional (3D) structures of Ebolavirus proteins, to study their interaction with host proteins, and to identify the functional motifs in these viral proteins. Here, in light of these experimental results, we apply computational analysis to predict the 3D structures and functional sites for Ebolavirus protein domains with unknown structure, including a zinc-finger domain of VP30, the RNA-dependent RNA polymerase catalytic domain and a methyltransferase domain of protein L. In addition, we compare sequences of proteins that interact with Ebolavirus proteins from RESTV-resistant primates with those from RESTV-susceptible monkeys. The host proteins that interact with GP and VP35 show an elevated level of sequence divergence between the RESTV resistant and RESTV-susceptible species, suggesting that they may be responsible for host specificity. Meanwhile, we detect variable positions in protein sequences that are likely associated with the loss of human pathogenicity in RESTV, map them onto the 3D structures and compare their positions to known functional sites. VP35 and VP30 are significantly enriched in these potential pathogenicity determinants and the clustering of such positions on the surfaces of VP35 and GP suggests possible uncharacterized interaction sites with host proteins that contribute to the virulence of Ebolavirus. PMID- 26158398 TI - Impact of sorafenib dosing on outcome from the European patient subset of the GIDEON study. AB - AIMS: To evaluate sorafenib dosing and safety in the Global Investigation of therapeutic GIDEON study's European subpopulation. PATIENTS & METHODS: Patient demographics, disease characteristics and treatment history were recorded at enrollment; dose, adverse events and efficacy were recorded at follow-up. RESULTS: Of 1113 evaluable patients, 82% started on 800 mg/day sorafenib; patients starting on 400 mg/day were slightly older, had baseline characteristics indicative of greater disease progression and higher adverse events incidences (96 vs 88%). Treatment duration (18.0 vs 13.0 weeks) and median overall survival (12.1 vs 9.4 months) were longer in patients receiving 800 mg/day. CONCLUSION: Imbalances in independent predictive factors may have led to longer survival in patients receiving 800 mg/day sorafenib; nonetheless, results suggest that the majority can start on this dose. PMID- 26158399 TI - Polarization influence on reflectance measurements in the spatial frequency domain. AB - In this work, we quantify the influence of crossed polarizers on reflectance measurements in the spatial frequency domain. The use of crossed polarizers is a very common approach for suppression of specular surface reflections. However, measurements are typically evaluated using a non-polarized scalar theory. The consequences of this discrepancy are the focus of our study, and we also quantify the related errors of the derived optical properties. We used polarized Monte Carlo simulations for forward calculation of the reflectance from different samples. The samples' scatterers are assumed to be spherical, allowing for the calculation of the scattering functions by Mie theory. From the forward calculations, the reduced scattering coefficient [Formula: see text] and the absorption coefficient MUa were derived by means of a scalar theory, as commonly used. Here, we use the analytical solution of the scalar radiative transfer equation. With this evaluation approach, which does not consider polarization, we found large errors in [Formula: see text] and MUa in the range of 25% and above. Furthermore, we investigated the applicability of the use of a reference measurement to reduce these errors as suggested in literature. We found that this method is not able to generally improve the accuracy of measurements in the spatial frequency domain. Our general recommendation is to apply a polarized theory when using crossed polarizers. PMID- 26158400 TI - Understanding physicians' professional knowledge and practice in research on skilled migration. AB - Research on the integration of migrant professionals into high-skilled labor markets either focuses on differences between nation states which may be exacerbated by national closure or it celebrates the global versatility of professional knowledge, especially in the natural and health sciences. Building on a pragmatist approach to professional knowledge, the article argues that professional knowledge should not be seen as either universal or local, but both the institutionalized and the incorporated aspects of cultural capital are characterized by 'local universality'. Professionals recreate professional knowledge in specific 'local' situations by relating to universal standards and to internalized 'libraries' of situated expert experience. While the more common notion of knowledge as a socially contested resource continues to be relevant for research on skilled migration, professional knowledge should also be seen as emerging in situations in response to socio-material problems. These problems can be structured by the nation-state, but they can also be transnational in nature. PMID- 26158401 TI - Vaccinations in prisons: A shot in the arm for community health. AB - From the first day of imprisonment, prisoners are exposed to and expose other prisoners to various communicable diseases, many of which are vaccine preventable. The risk of acquiring these diseases during the prison sentence exceeds that of the general population. This excess risk may be explained by various causes; some due to the structural and logistical problems of prisons and others to habitual or acquired behaviors during imprisonment. Prison is, for many inmates, an opportunity to access health care, and is therefore an ideal opportunity to update adult vaccination schedules. The traditional idea that prisons are intended to ensure public safety should be complemented by the contribution they can make in improving community health, providing a more comprehensive vision of safety that includes public health. PMID- 26158402 TI - Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients. AB - RATIONALE: Tools that screen inpatients for sepsis use the systemic inflammatory response syndrome (SIRS) criteria and organ dysfunctions, but most studies of these criteria were performed in intensive care unit or emergency room populations. OBJECTIVES: To determine the incidence and prognostic value of SIRS and organ dysfunctions in a multicenter dataset of hospitalized ward patients. METHODS: Hospitalized ward patients at five hospitals from November 2008 to January 2013 were included. SIRS and organ system dysfunctions were defined using 2001 International Consensus criteria. Patient characteristics and in-hospital mortality were compared among patients meeting two or more SIRS criteria and by the presence or absence of organ system dysfunction. MEASUREMENTS AND MAIN RESULTS: A total of 269,951 patients were included in the study, after excluding 48 patients with missing discharge status. Forty-seven percent (n = 125,841) of the included patients met two or more SIRS criteria at least once during their ward stay. On ward admission, 39,105 (14.5%) patients met two or more SIRS criteria, and patients presenting with SIRS had higher in-hospital mortality than those without SIRS (4.3% vs. 1.2%; P < 0.001). Fourteen percent of patients (n = 36,767) had at least one organ dysfunction at ward admission, and those presenting with organ dysfunction had increased mortality compared with those without organ dysfunction (5.3% vs. 1.1%; P < 0.001). CONCLUSIONS: Almost half of patients hospitalized on the wards developed SIRS at least once during their ward stay. Our findings suggest that screening ward patients using SIRS criteria for identifying those with sepsis would be impractical. PMID- 26158403 TI - Development and preliminary evaluation of a new test of ongoing speech comprehension. AB - OBJECTIVE: The overall goal of this work is to create new speech perception tests that more closely resemble real world communication and offer an alternative or complement to the commonly used sentence recall test. DESIGN: We describe the development of a new ongoing speech comprehension test based on short everyday passages and on-the-go questions. We also describe the results of an experiment conducted to compare the psychometric properties of this test to those of a sentence test. STUDY SAMPLE: Both tests were completed by a group of listeners that included normal hearers as well as hearing-impaired listeners who participated with and without their hearing aids. RESULTS: Overall, the psychometric properties of the two tests were similar, and thresholds were significantly correlated. However, there was some evidence of age/cognitive effects in the comprehension test that were not revealed by the sentence test. CONCLUSIONS: This new comprehension test promises to be useful for the larger goal of creating laboratory tests that combine realistic acoustic environments with realistic communication tasks. Further efforts will be required to assess whether the test can ultimately improve predictions of real-world outcomes. PMID- 26158404 TI - Dual Screening of BPTF and Brd4 Using Protein-Observed Fluorine NMR Uncovers New Bromodomain Probe Molecules. AB - Bromodomain-containing protein dysregulation is linked to cancer, diabetes, and inflammation. Selective inhibition of bromodomain function is a newly proposed therapeutic strategy. We describe a (19)F NMR dual screening method for small molecule discovery using fluorinated tryptophan resonances on two bromodomain containing proteins. The chemical shift dispersion of (19)F resonances within fluorine-labeled proteins enables the simultaneous analysis of two fluorinated bromodomains by NMR. A library of 229 small molecules was screened against the first bromodomain of Brd4 and the BPTF bromodomain. We report the first small molecule selective for BPTF over Brd4, termed AU1. The Kd = 2.8 MUM for AU1, which is active in a cell-based reporter assay. No binding is detected with Brd4. Three new Brd4 inhibitors with submicromolar affinity were also discovered. Brd4 hits were validated in a thermal stability assay and potency determined via fluorescence anisotropy. The speed, ease of interpretation, and low protein concentration needed for protein-observed (19)F NMR experiments in a multiprotein format offers a new method to discover and characterize selective ligands for bromodomain-containing proteins. PMID- 26158405 TI - Simultaneous Quantification of Methylated Cytidine and Adenosine in Cellular and Tissue RNA by Nano-Flow Liquid Chromatography-Tandem Mass Spectrometry Coupled with the Stable Isotope-Dilution Method. AB - The rising interest in understanding the functions, regulation, and maintenance of the epitranscriptome calls for robust and accurate analytical methods for the identification and quantification of post-transcriptionally modified nucleosides in RNA. Monomethylations of cytidine and adenosine are common post transcriptional modifications in RNA. Herein, we developed an LC-MS/MS/MS coupled with the stable isotope-dilution method for the sensitive and accurate quantifications of 5-methylcytidine (m(5)C), 2'-O-methylcytidine (Cm), N(6) methyladenosine (m(6)A), and 2'-O-methyladenosine (Am) in RNA isolated from mammalian cells and tissues. Our results showed that the distributions of m(5)C, Cm and Am are tissue-specific. In addition, the 2'-O-methylated ribonucleosides (Cm and Am) are present at higher levels than the corresponding methylated nucleobase products (m(5)C and m(6)A) in total RNA isolated from mouse brain, pancreas, and spleen but not mouse heart. We also found that the levels of m(5)C, Cm, and Am are significantly lower (by 6.5-43-fold) in mRNA than in total RNA isolated from HEK293T cells, whereas the level of m(6)A was slightly higher (by 1.6-fold) in mRNA than in total RNA. The availability of this analytical method, in combination with genetic manipulation, may facilitate the future discovery of proteins involved in the maintenance and regulation of these RNA modifications. PMID- 26158407 TI - An ethane-bridged porphyrin dimer as a model of di-heme proteins: inorganic and bioinorganic perspectives and consequences of heme-heme interactions. AB - Interaction between heme centers has been cleverly implemented by Nature in order to regulate different properties of multiheme cytochromes, thereby allowing them to perform a wide variety of functions. Our broad interest lies in unmasking the roles played by heme-heme interactions in modulating different properties viz., metal spin state, redox potential etc., of the individual heme centers using an ethane-bridged porphyrin dimer as a synthetic model of dihemes. The large differences in the structure and properties of the diheme complexes, as compared to the monoheme analogs, provide unequivocal evidence of the role played by heme heme interactions in the dihemes. This Perspective provides a brief account of our recent efforts to explore these interesting aspects and the subsequent outcomes. PMID- 26158408 TI - Divergent synthesis of various iminocyclitols from D-ribose. AB - A very efficient route to the diastereoselective synthesis of polyhydroxy pyrrolidines, piperidines and azepanes from an aldehyde derivative of ribose is reported. Asymmetric alpha-amination of aldehydes using proline catalysed hydrazination is the key step in the synthesis. The method utilizes the stereocenters present in ribose and the extra carbon atoms present in the target molecules are incorporated using Wittig reactions. The incorporation of the amino group is carried out asymmetrically to account for additional stereocenters. This synthetic route to iminocyclitols has the potential to be extended for the synthesis of a large class of such compounds starting from other sugar derived aldehydes. PMID- 26158406 TI - Agent-based model of angiogenesis simulates capillary sprout initiation in multicellular networks. AB - Many biological processes are controlled by both deterministic and stochastic influences. However, efforts to model these systems often rely on either purely stochastic or purely rule-based methods. To better understand the balance between stochasticity and determinism in biological processes a computational approach that incorporates both influences may afford additional insight into underlying biological mechanisms that give rise to emergent system properties. We apply a combined approach to the simulation and study of angiogenesis, the growth of new blood vessels from existing networks. This complex multicellular process begins with selection of an initiating endothelial cell, or tip cell, which sprouts from the parent vessels in response to stimulation by exogenous cues. We have constructed an agent-based model of sprouting angiogenesis to evaluate endothelial cell sprout initiation frequency and location, and we have experimentally validated it using high-resolution time-lapse confocal microscopy. ABM simulations were then compared to a Monte Carlo model, revealing that purely stochastic simulations could not generate sprout locations as accurately as the rule-informed agent-based model. These findings support the use of rule-based approaches for modeling the complex mechanisms underlying sprouting angiogenesis over purely stochastic methods. PMID- 26158409 TI - Laser-induced breakdown detection of temperature-ramp generated aggregates of therapeutic monoclonal antibody. AB - The detection and characterization of protein aggregation is essential during development and quality control of therapeutic proteins, as aggregates are typically inactive and may trigger anti-drug-antibody formation in patients. Especially large multi-domain molecules, such as the important class of therapeutic monoclonal antibodies (mAbs), can form various aggregates that differ in size and morphology. Although particle analysis advanced over the recent years, new techniques and orthogonal methods are highly valued. To our knowledge, the physical principle of laser-induced breakdown detection (LIBD) was not yet applied to sense aggregates in therapeutic protein formulations. We established a LIBD setup to monitor the temperature-induced aggregation of a mAb. The obtained temperature of aggregation was in good agreement with the results from previously published temperature-ramped turbidity and dynamic light scattering measurements. This study demonstrates the promising applicability of LIBD to investigate aggregates from therapeutic proteins. The technique is also adaptive to online detection and size determination, and offers interesting opportunities for morphologic characterization of protein particles and impurities, which will be part of future studies. PMID- 26158410 TI - MYC or BCL2 copy number aberration is a strong predictor of outcome in patients with diffuse large B-cell lymphoma. AB - Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). Patients with DLBCL harboring MYC aberrations concurrent with BCL2 or/and BCL6 aberrations constitute a specific group with extremely poor outcome. In this study, we retrospectively investigated the incidence and prognosis of MYC, BCL2, and BCL6 aberrations with DLBCL patients in Chinese population. We applied fluorescence in situ hybridization and immunohistochemical analysis in 246 DLBCL patients. The results showed that patients with MYC or BCL2 copy number aberration (CNA) had significantly worse overall survival (OS) and progression free survival (PFS) than negative cases (P < 0.0001). Patients with both MYC and BCL2 CNA had similar outcomes to those with classic double hit lymphoma or protein double expression lymphoma (MYC and BCL2/BCL6 coexpression). By multivariate analysis, MYC CNA, BCL2 CNA and double CNA were the independent worse prognostic factors. In conclusions, patients with MYC or BCL2 CNA constituted a unique group with extremely poor outcome and may require more aggressive treatment regimens. PMID- 26158411 TI - Transcriptome profiling of esophageal squamous cell carcinoma reveals a long noncoding RNA acting as a tumor suppressor. AB - Esophageal Squamous Cell Carcinoma (ESCC) is among the most common malignant cancers worldwide. In the past, extensive efforts have been made to characterize the involvement of protein-coding genes in ESCC tumorigenesis but few for long noncoding RNAs (lncRNAs). To investigate the transcriptome profile and functional relevance of lncRNAs, we performed an integrative analysis of a customized combined lncRNA-mRNA microarray and RNA-seq data on ESCCs and matched normal tissues. We identified numerous lncRNAs that were differentially expressed between the normal and tumor tissues, termed "ESCC-associated lncRNAs (ESCALs)", of which, the majority displayed restricted expression pattern. Also, a subset of ESCALs appeared to be associated with ESCC patient survival. Gene set enrichment analysis (GSEA) further suggested that over half of the ESCALs were positively-or negatively-associated with metastasis. Among these, we identified a novel nuclear retained lncRNA, named Epist, which is generally highly expressed in esophagus, and which is down-regulated during ESCC progression. Epist over-expression and knockdown studies further suggest that Epist inhibits the metastasis, acting as a tumor suppressor in ESCC. Collectively, our analysis of the ESCC transcriptome identified the potential tumor suppressing lncRNA Epist, and provided a foundation for future efforts to identify functional lncRNAs for cancerous therapeutic targeting. PMID- 26158412 TI - A MEK/PI3K/HDAC inhibitor combination therapy for KRAS mutant pancreatic cancer cells. AB - Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, metastatic disease with limited treatment options. Factors contributing to the metastatic predisposition and therapy resistance in pancreatic cancer are not well understood. Here, we used a mouse model of KRAS-driven pancreatic carcinogenesis to define distinct subtypes of PDAC metastasis: epithelial, mesenchymal and quasi mesenchymal. We examined pro-survival signals in these cells and the therapeutic response differences between them. Our data indicate that the initiation and maintenance of the transformed state are separable, and that KRAS dependency is not a fundamental constant of KRAS-initiated tumors. Moreover, some cancer cells can shuttle between the KRAS dependent (drug-sensitive) and independent (drug tolerant) states and thus escape extinction. We further demonstrate that inhibition of KRAS signaling alone via co-targeting the MAPK and PI3K pathways fails to induce extensive tumor cell death and, therefore, has limited efficacy against PDAC. However, the addition of histone deacetylase (HDAC) inhibitors greatly improves outcomes, reduces the self-renewal of cancer cells, and blocks cancer metastasis in vivo. Our results suggest that targeting HDACs in combination with KRAS or its effector pathways provides an effective strategy for the treatment of PDAC. PMID- 26158414 TI - Flawed validation of FRAX. PMID- 26158415 TI - Influence of Isolation Method of the Operative Field on Gingival Damage, Patients' Preference, and Restoration Retention in Noncarious Cervical Lesions. AB - OBJECTIVES: To evaluate the retention rates, gingival damage, and patients' preferences for adhesive restorations in noncarious cervical lesions (NCCL) associated with the use of rubber dam vs cotton rolls/retraction cord isolation. METHODS: Thirty patients having one pair of similar NCCL on opposing sides of the same arch were enrolled in this study. A total of 60 restorations were placed. In each patient one restoration was placed under rubber dam isolation (RD) using dental retainers, and the other one was placed using cotton rolls/retraction cord (CR/RC) isolation. Dental residents with more than 10 years of clinical experience restored all NCCL using the same adhesive (GO!, SDI Limited, Bayswater, Australia) and composite resin (Ice, SDI). The patients' preferences were recorded. The gingival condition (bleeding, gingival laceration, and gingival insertion level) was evaluated immediately after the restorative procedure and after one week. Gingival sensitivity was also assessed one week after the end of the restorative procedures. The clinical time required to perform each restoration was recorded. The performance of the restorations was assessed using the FDI criteria at baseline and six, 12, and 18 months after clinical service. All criteria evaluated were submitted to appropriate statistical analysis (alpha=0.05). RESULTS: The retention rates of the restorations at each recall time were not affected by the isolation method (p>0.05). No significant difference between isolation methods was found in regard to patients' preferences (p=0.86), gingival bleeding (p=0.57), laceration (p=0.64), insertion (p>0.52), gingival sensitivity (p=0.52), or chairside time (p=0.77). CONCLUSIONS: The use of CR/RC was shown to be similar to the use of RD in terms of retention rates, patient's preference, gingival damage, and chairside time for adhesive restorations in NCCL. PMID- 26158413 TI - TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney. AB - Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified. One tumor with t(10;17)(q22;p13) involving fusion of YHWAE with NUTM2B was identified. Integrated analysis of expression and methylation data identified promoter hypermethylation and low expression of the tumor suppressor gene TCF21 (Pod-1/capsulin/epicardin) in all CCSKs except the case with t(10;17)(q22;p13). TARID, the long noncoding RNA responsible for demethylating TCF21, was virtually undetectable in most CCSKs. TCF21 hypermethylation and decreased TARID expression were validated in an independent set of CCSK tumor samples. The presence of significant hypermethylation of TCF21, a transcription factor known to be active early in renal development, supports the hypothesis that hypermethylation of TCF21 and/or decreased TARID expression lies within the pathogenic pathway of most CCSKs. Future studies are needed to functionally verify a tumorigenic role of TCF21 down-regulation and to tie this to the unique gene expression pattern of CCSK. PMID- 26158421 TI - MicroRNAs in cancer: from developmental genes in worms to their clinical application in patients. AB - Several discoveries have paved the way to personalise cancer medicine and a tremendous gain of knowledge in genomics and molecular mechanisms of cancer progression cumulated over the last years. Big stories in biology commonly start in a simple model system. No wonder microRNAs have been identified as regulators of embryonic development in the nematode Caenorhabditis elegans. From the first identification in worms to the first-in-man microRNA-based clinical trial in humans, almost 20 years passed. In this review we follow the story of understanding microRNA alterations in cancer, describe recent developments in the microRNA field and critically discuss their potential as diagnostic, prognostic and therapeutics factors in cancer medicine. We will explain the rationale behind the use of microRNAs in cancer diagnosis and prognosis prediction, but also discuss the limitations and pitfalls associated with this. Novel developments of combined microRNA/siRNA pharmacological approaches will be discussed and most recently data about MXR34, the first-tested microRNA drug will be described. PMID- 26158416 TI - Cerebellar associative sensory learning defects in five mouse autism models. AB - Sensory integration difficulties have been reported in autism, but their underlying brain-circuit mechanisms are underexplored. Using five autism-related mouse models, Shank3+/DeltaC, Mecp2(R308/Y), Cntnap2-/-, L7-Tsc1 (L7/Pcp2(Cre)::Tsc1(flox/+)), and patDp(15q11-13)/+, we report specific perturbations in delay eyeblink conditioning, a form of associative sensory learning requiring cerebellar plasticity. By distinguishing perturbations in the probability and characteristics of learned responses, we found that probability was reduced in Cntnap2-/-, patDp(15q11-13)/+, and L7/Pcp2(Cre)::Tsc1(flox/+), which are associated with Purkinje-cell/deep-nuclear gene expression, along with Shank3+/DeltaC. Amplitudes were smaller in L7/Pcp2(Cre)::Tsc1(flox/+) as well as Shank3+/DeltaC and Mecp2(R308/Y), which are associated with granule cell pathway expression. Shank3+/DeltaC and Mecp2(R308/Y) also showed aberrant response timing and reduced Purkinje-cell dendritic spine density. Overall, our observations are potentially accounted for by defects in instructed learning in the olivocerebellar loop and response representation in the granule cell pathway. Our findings indicate that defects in associative temporal binding of sensory events are widespread in autism mouse models. PMID- 26158422 TI - Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland. AB - BACKGROUND: Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. METHODS: Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. RESULTS: In a population of 2.4 million, over a 10 year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P?0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos screening, P?0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P?0.001). CONCLUSIONS: Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer. PMID- 26158423 TI - Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer. AB - BACKGROUND: RNA-binding proteins have an important role in messenger RNA (mRNA) regulation during tumour development and carcinogenesis. In the present study, we examined the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; hereafter refered to as IMPs) and Lin28 family expressions in epithelial ovarian carcinoma (EOC) patients and correlated their expression levels with the response to chemotherapy, hCTR1 expression and patient survival. METHODS: Patients clinical information, real-time RT-PCR, immunohistochemistry, western blot, Transwell migration invasion assays, and cytotoxicity assays were used. RESULTS: From 140 EOC patients, high expression of IMP3 or Lin28B was associated with poor survival, and women diagnosed at advanced stages with elevated IMP3 and Lin28B were at higher risk of developing chemoresistance. High IMP3 levels combined with high Lin28B levels significantly correlated with the poorest 5-year survival rates. Knockdown of IMP3 or Lin28B decreased cell proliferation, migration, and invasion, and increased the platinum sensitivity, but not taxol sensitivity, of ovarian cancer cells through increased expression of hCTR1, a copper transporter involved in platinum uptake. High expression of hCTR1 correlated with low expression of IMP3/Lin28B and better progression-free survival in advanced-stage EOC patients. CONCLUSION: Testing for a combination of elevated IMP3 and Lin28B levels could further facilitate the identification of a patient subgroup with the worst prognosis. PMID- 26158426 TI - Anxiety among older psychiatric patients: a hidden comorbidity? AB - OBJECTIVES: Our aims were to explore prevalence of anxiety among patients admitted to departments of geriatric psychiatry for treatment of various diagnoses and to examine how often anxiety was registered as a previous or ongoing diagnosis. METHOD: In all, 473 patients admitted to one of five departments of geriatric psychiatry were included in a quality register and examined according to a standardized protocol. The Geriatric Anxiety Inventory (GAI) was used to measure anxiety during the first week after admission. Diagnoses were made at discharge. RESULTS: Using a cutoff on the GAI of 8/9, the prevalence of anxiety for the following diagnostic groups was depression 65.3%, psychosis 28%, dementia 38.8% and mania 33.3%. Of 24 patients with a primary diagnosis of anxiety, 66.7% scored above 8 on the GAI. Of 236 patients with a GAI score above 8, only 22 (9.3%) were reported to have a comorbid anxiety disorder by the treating psychiatrist. In a multiple regression analysis, we found that the severity of depression (beta 0.585, p < 0.001), being female (beta 0.096, p 0.028) and the use of antipsychotic drugs (beta 0.129, p 0.006) and anxiolytic drugs (beta 0.129, p 0.005) were associated with a higher GAI score. CONCLUSION: Anxiety is common in geriatric psychiatric patients, regardless of the primary diagnosis. Our findings suggest that anxiety is often a hidden comorbidity in various psychiatric disorders. A high score on the GAI was associated with the severity of depression, female gender and the use of antipsychotic and anxiolytic drugs. PMID- 26158425 TI - Pre-existing diabetes and breast cancer prognosis among elderly women. AB - BACKGROUND: The objective of this study was to assess the impact of pre-existing diabetes on breast cancer prognosis. METHODS: Women (n=2833) with centrally confirmed invasive breast cancer in the Women's Health Initiative, who were linked to Medicare claims data (CMS) were followed from the date of breast cancer diagnosis to date of death or 20 September 2013. Information on diabetes was identified through the CMS Chronic Condition Warehouse algorithm. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. A competing risks model (proportional subdistribution) model was used to estimate hazard ratios for breast cancer-specific mortality. RESULTS: Women with diabetes were more likely to have factors related to delayed diagnosis (less recent mammograms, and more advanced cancer stage) and were less likely to receive radiation therapy. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR=1.57, 95% CI: 1.23-2.01) and had nonsignificantly increased risk for breast cancer-specific mortality (HR=1.36, 95% CI: 0.86-2.15) before adjustment for factors related to delayed diagnosis and treatment. Adjustment for these factors resulted in a little change in the association of diabetes with overall mortality risk, but further attenuated the point estimate for breast cancer-specific mortality. CONCLUSIONS: Our study provides additional evidence that pre-existing diabetes increases the risk of total mortality among women with breast cancer. Very large studies with data on breast cancer risk factors, screening and diagnostic delays, treatment choices, and the biological influence of diabetes on breast cancer will be needed to determine whether diabetes also increases the risk for breast cancer specific mortality. PMID- 26158424 TI - Clinical utility of RASSF1A methylation in human malignancies. AB - The high frequency of RASSF1A methylation has been noted in a vast number of patients in a broad spectrum of malignancies, suggesting that RASSF1A inactivation is associated with cancer pathogenesis. However, whether this recurrent incidence of RASSF1A hypermethylation in human malignancies and its association with more aggressive tumour phenotype is a frequent event across different cancer types has not yet been discussed. In this review, we interrogated existing evidence for association of RASSF1A hypermethylation with clinicopathological characteristics that can indicate more invasive lesions. PMID- 26158427 TI - An SN1-type Reaction To Form the 1,2-Dioxepane Ring: Synthesis of 10,12 Peroxycalamenene. AB - The synthesis of the sesquiterpene endoperoxide natural product 10,12 peroxycalamenene has been achieved. Featured transformations include an intramolecular Heck reaction to build the fused bicyclic core and a cobalt catalyzed peroxidation to install the peroxide functional group. The final step involved an SN1-type ring closure catalyzed by DDQ to construct the 1,2-dioxepane ring. PMID- 26158428 TI - Bonding Study on the Chemical Separation of Am(III) from Eu(III) by S-, N-, and O Donor Ligands by Means of All-Electron ZORA-DFT Calculation. AB - We performed a theoretical investigation for the selectivity of Eu(III)/Am(III) ions depending on the donor atoms by means of all-electron ZORA-DFT calculation. We estimated their selectivity as the relative stability in the complex formation reaction. The B2PLYP functional reproduced the experimental selectivity in which S- and N-donor ligands favor Am(III) ion, but O-donor ligand favors Eu(III) ion. Mulliken's bond overlap population analysis revealed that the contribution of the f orbital to the bonding was small or zero for Eu complex, whereas it was large for Am complex. The bonding nature of the f orbital for Am ion was the bonding type to S- and N-donor ligands, while it was the antibonding type to O-donor ligand. It was suggested that the difference in the bonding nature between the f orbital in the metal and the donor atoms determines the selectivity of Eu(III)/Am(III) by donor ligands. PMID- 26158429 TI - Thermally activated delayed fluorescence sensitized phosphorescence: a strategy to break the trade-off between efficiency and efficiency roll-off. AB - Materials with thermally activated delayed fluorescence (TADF) realized 100% internal quantum efficiency (IQE) but suffered significant efficiency roll-off. Here, an exciton dynamics study reveals that materials with TADF may play opposite roles in affecting the efficiency roll-off: decreasing the triplet density due to the fast reverse intersystem crossing, on the one hand, and increasing the triplet density due to the weakened singlet radiation. We show theoretically and experimentally that TADF-sensitized phosphorescence can break this trade-off by exploiting the efficient Forster energy transfer and simultaneously achieve 100% IQE and low efficiency roll-off (with a critical current density of 460 mA cm(-2)). PMID- 26158430 TI - A Three-Step Scenario Involved in Particle Capture on a Pore Edge. AB - A scenario is proposed to describe the capture of a spherical particle around a cylindrical pore. This geometry, "ideal" as far as the problem of particle capture on a filtration membrane is concerned, is clearly relevant in view of the pore-scale geometry of nucleopore or microsieve filtration membranes, and also of some microfluidic systems used to perform fluid-particle separation. The present scenario consists of three successive steps: particle deposition on the membrane away from the pore, subsequent reentrainment of some of the deposited particles by rolling on the membrane surface, and final arrest by a stabilizing van der Waals torque when the particle rolls over the pore edge. A modeling of these three steps requires the hydrodynamic and physicochemical particle-membrane interactions to be detailed close to the singular pore edge region and raises questions concerning the role of particle surface roughness. The relevance and robustness of such of a scenario for rough micrometer-sized latex particles is emphasized and comparisons are made with existing experimental data. PMID- 26158432 TI - Light-Emitting Self-Assembled Materials Based on d(8) and d(10) Transition Metal Complexes. PMID- 26158431 TI - Point nodes persisting far beyond Tc in Bi2212. AB - In contrast to a complex feature of antinodal state, suffering from competing orders, the pairing gap of cuprates is obtained in the nodal region, which therefore holds the key to the superconducting mechanism. One of the biggest question is whether the point nodal state as a hallmark of d-wave pairing collapses at Tc like the BCS-type superconductors, or it instead survives above Tc turning into the preformed pair state. A difficulty in this issue comes from the small magnitude of the nodal gap, which has been preventing experimentalists from solving it. Here we use a laser ARPES capable of ultrahigh-energy resolution, and detect the point nodes surviving far beyond Tc in Bi2212. By tracking the temperature evolution of spectra, we reveal that the superconductivity occurs when the pair-breaking rate is suppressed smaller than the single-particle scattering rate on cooling, which governs the value of Tc in cuprates. PMID- 26158435 TI - Diplopia After a Sinus Infection. PMID- 26158436 TI - Bilateral Eyelid Nodules Impairing Eyelid Closure in 2 Siblings. PMID- 26158437 TI - Moniliform Blepharosis of Lipoid Proteinosis. PMID- 26158438 TI - Synchysis Scintillans in a Child. PMID- 26158439 TI - Silicone Oil Confined Within a Lamellar Macular Hole as Demonstrated by En Face Swept Source Optical Coherence Tomography. PMID- 26158440 TI - Invisible Retinoblastoma. PMID- 26158441 TI - Randomized Trial of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration With and Without Rapid On-site Evaluation for Lung Cancer Genotyping. AB - BACKGROUND: Experts and scientific society guidelines recommend that rapid on site evaluation (ROSE) be used with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to optimize lung cancer genotyping, but no comparative trial has been carried out to confirm and quantify its usefulness. METHODS: To assess the influence of ROSE on the yield of EBUS-TBNA for a multigene molecular analysis of lung cancer samples, consecutive patients with suspected or known advanced lung cancer were randomized to undergo EBUS-TBNA without ROSE (EBUS arm) or with ROSE (ROSE arm). The primary end point was the rate of the successful accomplishment of the institution's clinical protocol for molecular profiling of nonsquamous non-small cell lung cancer (EGFR and KRAS testing, followed by ALK testing for tumors with EGFR and KRAS wild-type status). RESULTS: Complete genotyping was achieved in 108 of 126 patients (85.7%) (90.8% in the ROSE arm vs 80.3% in the EBUS arm, P = .09). The patients in the ROSE arm were less likely to have samples that could be used only for pathologic diagnosis because of minimal tumor burden (0 vs 6, P = .05), and were more likely to have the bronchoscopy terminated after a single biopsy site (58.9% vs 44.1%, P = .01). CONCLUSIONS: ROSE prevents the need for a repeat invasive diagnostic procedure aimed at molecular profiling in at least one out of 10 patients with advanced lung cancer and significantly reduces the risk of retrieving samples that can be used only for pathologic subtyping because of minimal tumor burden. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01799382; URL: www.clinicaltrials.gov. PMID- 26158442 TI - In vitro and in vivo generation and characterization of Pseudomonas aeruginosa biofilm-dispersed cells via c-di-GMP manipulation. AB - Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a global secondary bacterial messenger that controls the formation of drug-resistant multicellular biofilms. Lowering the intracellular c-di-GMP content can disperse biofilms, and it is proposed as a biofilm eradication strategy. However, freshly dispersed biofilm cells exhibit a physiology distinct from biofilm and planktonic cells, and they might have a clinically relevant role in infections. Here we present in vitro and in vivo protocols for the generation and characterization of dispersed cells from Pseudomonas aeruginosa biofilms by reducing the intracellular c-di-GMP content through modulation of phosphodiesterases (PDEs). Unlike conventional protocols that demonstrate biofilm dispersal by biomass quantification, our protocols enable physiological characterization of the dispersed cells. Biomarkers of dispersed cells are identified and quantified, serving as potential targets for treating the dispersed cells. The in vitro protocol can be completed within 4 d, whereas the in vivo protocol requires 7 d. PMID- 26158444 TI - Risk of angle-closure glaucoma with bupropion and topiramate. AB - IMPORTANCE: Epidemiologic studies have shown that antidepressants may increase the risk of angle-closure glaucoma. We examined the risk of angle-closure glaucoma with bupropion hydrochloride, a unique, popular antidepressant also marketed as a smoking cessation aid. OBSERVATIONS: A nested case-control study was conducted using a large health claims database in the United States from January 1, 2006, to March 31, 2014. The database contained deidentified information pertaining to a cohort of 6 110 723 patients. Cases were defined according to the first coding for angle-closure glaucoma. For each case, 10 control participants were selected and matched to the cases using density-based sampling. Adjusted rate ratios were computed for bupropion, topiramate (positive control group drug), and esomeprazole (negative control group drug). The adjusted rate ratio was 1.09 (95% CI, 0.75-1.59) for bupropion and 2.59 (95% CI, 1.56 4.30) for topiramate. In a prespecified analysis of patients younger than 50 years, the adjusted rate ratio was 1.98 (95% CI, 1.02-3.84) for bupropion and 5.30 (95% CI, 2.54-11.04) for topiramate. CONCLUSIONS AND RELEVANCE: Both bupropion and topiramate are widely prescribed drugs. The risk of angle-closure glaucoma in patients younger than 50 years was twice as high in patients taking bupropion and more than 5 times higher in patients taking topiramate. PMID- 26158443 TI - High-throughput microfluidics to control and measure signaling dynamics in single yeast cells. AB - Microfluidics coupled to quantitative time-lapse fluorescence microscopy is transforming our ability to control, measure and understand signaling dynamics in single living cells. Here we describe a pipeline that incorporates multiplexed microfluidic cell culture, automated programmable fluid handling for cell perturbation, quantitative time-lapse microscopy and computational analysis of time-lapse movies. We illustrate how this setup can be used to control the nuclear localization of the budding yeast transcription factor Msn2. By using this protocol, we generate oscillations of Msn2 localization and measure the dynamic gene expression response of individual genes in single cells. The protocol allows a single researcher to perform up to 20 different experiments in a single day, while collecting data for thousands of single cells. Compared with other protocols, the present protocol is relatively easy to adopt and of higher throughput. The protocol can be widely used to control and monitor single-cell signaling dynamics in other signal transduction systems in microorganisms. PMID- 26158445 TI - PTEN regulates DNA replication progression and stalled fork recovery. AB - Faithful DNA replication is a cornerstone of genomic integrity. PTEN plays multiple roles in genome protection and tumour suppression. Here we report on the importance of PTEN in DNA replication. PTEN depletion leads to impairment of replication progression and stalled fork recovery, indicating an elevation of endogenous replication stress. Exogenous replication inhibition aggravates replication-originated DNA lesions without inducing S phase arrest in cells lacking PTEN, representing replication stress tolerance. iPOND analysis reveals the physical association of PTEN with DNA replication forks and PTEN-dependent recruitment of Rad51. PTEN deletion results in Rad51 dissociation from replication forks. Stalled replication forks in Pten-null cells can be reactivated by ectopic Rad51 or PTEN, the latter facilitating chromatin loading of Rad51. These data highlight the interplay of PTEN with Rad51 in promoting stalled fork restart. We propose that loss of PTEN may initiate a replication stress cascade that progressively deteriorates through the cell cycle. PMID- 26158446 TI - Parentage Reconstruction in Eucalyptus nitens Using SNPs and Microsatellite Markers: A Comparative Analysis of Marker Data Power and Robustness. AB - Pedigree reconstruction using molecular markers enables efficient management of inbreeding in open-pollinated breeding strategies, replacing expensive and time consuming controlled pollination. This is particularly useful in preferentially outcrossed, insect pollinated Eucalypts known to suffer considerable inbreeding depression from related matings. A single nucleotide polymorphism (SNP) marker panel consisting of 106 markers was selected for pedigree reconstruction from the recently developed high-density Eucalyptus Infinium SNP chip (EuCHIP60K). The performance of this SNP panel for pedigree reconstruction in open-pollinated progenies of two Eucalyptus nitens seed orchards was compared with that of two microsatellite panels with 13 and 16 markers respectively. The SNP marker panel out-performed one of the microsatellite panels in the resolution power to reconstruct pedigrees and out-performed both panels with respect to data quality. Parentage of all but one offspring in each clonal seed orchard was correctly matched to the expected seed parent using the SNP marker panel, whereas parentage assignment to less than a third of the expected seed parents were supported using the 13-microsatellite panel. The 16-microsatellite panel supported all but one of the recorded seed parents, one better than the SNP panel, although there was still a considerable level of missing and inconsistent data. SNP marker data was considerably superior to microsatellite data in accuracy, reproducibility and robustness. Although microsatellites and SNPs data provide equivalent resolution for pedigree reconstruction, microsatellite analysis requires more time and experience to deal with the uncertainties of allele calling and faces challenges for data transferability across labs and over time. While microsatellite analysis will continue to be useful for some breeding tasks due to the high information content, existing infrastructure and low operating costs, the multi-species SNP resource available with the EuCHIP60k, opens a whole new array of opportunities for high-throughput, genome-wide or targeted genotyping in species of Eucalyptus. PMID- 26158447 TI - Layer by Layer Ex-Situ Deposited Cobalt-Manganese Oxide as Composite Electrode Material for Electrochemical Capacitor. AB - The composite metal oxide electrode films were fabricated using ex situ electrodeposition method with further heating treatment at 300 degrees C. The obtained composite metal oxide film had a spherical structure with mass loading from 0.13 to 0.21 mg cm(-2). The structure and elements of the composite was investigated using X-ray diffraction (XRD) and energy dispersive X-ray (EDX). The electrochemical performance of different composite metal oxides was studied by cyclic voltammetry (CV) and galvanostatic charge-discharge (CD). As an active electrode material for a supercapacitor, the Co-Mn composite electrode exhibits a specific capacitance of 285 Fg(-1) at current density of 1.85 Ag(-1) in 0.5 M Na2SO4 electrolyte. The best composite electrode, Co-Mn electrode was then further studied in various electrolytes (i.e., 0.5 M KOH and 0.5 M KOH/0.04 M K3Fe(CN) 6 electrolytes). The pseudocapacitive nature of the material of Co-Mn lead to a high specific capacitance of 2.2 x 10(3) Fg(-1) and an energy density of 309 Whkg(-1) in a 0.5 M KOH/0.04 M K3Fe(CN) 6 electrolyte at a current density of 10 Ag(-1). The specific capacitance retention obtained 67% of its initial value after 750 cycles. The results indicate that the ex situ deposited composite metal oxide nanoparticles have promising potential in future practical applications. PMID- 26158449 TI - When Life Got in the Way: How Danish and Norwegian Immigrant Women in Sweden Reason about Cervical Screening and Why They Postpone Attendance. AB - INTRODUCTION: Danish and Norwegian immigrant women in Sweden have an increased risk of cervical cancer compared to Swedish-born women. In addition, Danish and Norwegian immigrant women follow the national recommendations for attendance at cervical screening to much lesser extent than Swedish-born women. The aim of this study was to explore how Danish and Norwegian immigrant women in Sweden reason about attending cervical screening, focusing on women's perceptions as to why they and their compatriots do not attend. METHODS: Eight focus group discussions (FGDs) were conducted with Danish and Norwegian immigrant women living in Stockholm. The women were between 26 and 66 years of age at the time of the FGDs, and were aged between <1 and 48 years old when they immigrated to Sweden. A FGD guide was used, which included questions related to cervical screening, and obstacles and motivators to attend cervical screening. The FGDs were tape recorded and transcribed, and the results analysed according to the principles of qualitative content analysis. RESULTS: The main theme was "Women have a comprehensive rationale for postponing cervical screening, yet do not view themselves as non-attenders". Investigation of women's rationale for non attendance after being invited to cervical screening revealed some complex reasons related to immigration itself, including competing needs, organisational and structural factors and differences in mentality, but also reasons stemming from other factors. Postponing attendance at cervical screening was the category that linked all these factors as the reasons to why women did not attend to cervical screening according to the recommendations of the authorities. CONCLUSIONS: The rationale used to postpone cervical screening, in combination with the fact that women do not consider themselves to be non-attenders, indicates that they have not actively taken a stance against cervical screening, and reveals an opportunity to motivate these women to attend. PMID- 26158448 TI - Genome Modeling System: A Knowledge Management Platform for Genomics. AB - In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms. PMID- 26158451 TI - Screening for asymptomatic lymphogranuloma venereum co-infection in men who have sex with men newly diagnosed with HIV, hepatitis C or syphilis. AB - Patients diagnosed with lymphogranuloma venereum have high rates of co-infection with HIV, syphilis and hepatitis C. The aim of this enhanced surveillance was to screen all men who have sex with men (MSM) newly diagnosed with HIV, syphilis or hepatitis C for co-infection with asymptomatic lymphogranuloma venereum as part of the recommended sexual health screen. Of the 145 patients screened, 21 patients were diagnosed with rectal Chlamydia trachomatis, one with both rectal and urethral chlamydia and six with urethral chlamydia. One rectal chlamydia positive sample, when tested, was equivocal for lymphogranuloma venereum. Our data suggested that there was not a pool of asymptomatic lymphogranuloma venereum infection in MSM recently diagnosed with HIV, hepatitis C and syphilis. However, there have been recent reports of an increased incidence of asymptomatic lymphogranuloma venereum, raising the question whether lymphogranuloma venereum should be screened for in high risk asymptomatic MSM. The prevalence of asymptomatic rectal chlamydia infections was 19%. PMID- 26158452 TI - A Bayesian Shrinkage Approach for AMMI Models. AB - Linear-bilinear models, especially the additive main effects and multiplicative interaction (AMMI) model, are widely applicable to genotype-by-environment interaction (GEI) studies in plant breeding programs. These models allow a parsimonious modeling of GE interactions, retaining a small number of principal components in the analysis. However, one aspect of the AMMI model that is still debated is the selection criteria for determining the number of multiplicative terms required to describe the GE interaction pattern. Shrinkage estimators have been proposed as selection criteria for the GE interaction components. In this study, a Bayesian approach was combined with the AMMI model with shrinkage estimators for the principal components. A total of 55 maize genotypes were evaluated in nine different environments using a complete blocks design with three replicates. The results show that the traditional Bayesian AMMI model produces low shrinkage of singular values but avoids the usual pitfalls in determining the credible intervals in the biplot. On the other hand, Bayesian shrinkage AMMI models have difficulty with the credible interval for model parameters, but produce stronger shrinkage of the principal components, converging to GE matrices that have more shrinkage than those obtained using mixed models. This characteristic allowed more parsimonious models to be chosen, and resulted in models being selected that were similar to those obtained by the Cornelius F-test (alpha = 0.05) in traditional AMMI models and cross validation based on leave-one-out. This characteristic allowed more parsimonious models to be chosen and more GEI pattern retained on the first two components. The resulting model chosen by posterior distribution of singular value was also similar to those produced by the cross-validation approach in traditional AMMI models. Our method enables the estimation of credible interval for AMMI biplot plus the choice of AMMI model based on direct posterior distribution retaining more GEI pattern in the first components and discarding noise without Gaussian assumption as requested in F-based tests or deal with parametric problems as observed in traditional AMMI shrinkage method. PMID- 26158450 TI - CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination. AB - CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63-deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death, and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63-deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination. PMID- 26158453 TI - Sero-Prevalence of Rodent Pathogens in India. AB - Health monitoring is an integral part of laboratory animal quality standards. However, current or past prevalence data as well as regulatory requirements dictate the frequency, type and the expanse of health monitoring. In an effort to understand the prevalence of rodent pathogens in India, a preliminary study was carried out by sero-epidemiology. Sera samples obtained from 26 public and private animal facilities were analyzed for the presence of antibodies against minute virus of mice (MVM), ectromelia virus (ECTV), lymphocytic choriomeningitis virus (LCMV), mouse hepatitis virus (MHV), Sendai virus (SeV), and Mycoplasma pulmonis in mice, and SeV, rat parvo virus (RPV), Kilham's rat virus (KRV) and sialodacryoadenitis virus (SDAV) in rats, by sandwich ELISA. It was observed that MHV was the most prevalent agent followed by Mycoplasma pulmonis and MVM in mice, and SDAV followed by RPV were prevalent in rats. On the other hand, none of the samples were positive for ECTV in mice, or SeV or KRV in rats. Multiple infections were common in both mice and rats. The incidence of MHV and Mycoplasma pulmonis was higher in facilities maintained by public organizations than in vivaria of private organizations, although the difference was not statistically different. On the other hand the prevalence of rodent pathogens was significantly higher in the northern part of India than in the South. These studies form the groundwork for detailed sero-prevalence studies which should further lay the foundations for country-specific guidelines for health monitoring of laboratory animals. PMID- 26158454 TI - Principal Component Analysis of Conformation and Blood Marker Traits at Pre- and Post-Weaning Stages of Growth in F2 Crossbred Nigerian Indigenous X Landrace Pigs. AB - Linear body measurements and blood hematology and biochemistry parameters were taken on 92 and 15 grower pigs, respectively, chosen randomly from a crossbred F2 population of Nigerian Indigenous (NI) x Landrace pigs to evaluate body conformation and blood marker traits using a multivariate approach. For linear body measurements at pre-weaning stage (4 weeks old), two principal components accounted for 91.63% of the total variation in body conformation traits, while at post weaning stage (12 weeks old), one principal component accounted for 73.63% of the total variations in body conformation traits. The first factor (principal component) accounted for 72.34% of the total variance (body weight) while the second factor accounted for 19.29% (ear length) at pre-weaning stage. While at post-weaning stage only one factor contributed to the total variability of the original six traits tested, with 73.63% (body length). For blood parameters, three principal components accounted for 81.85% of the total variation at pre weaning stage while 89.44% of the total variation at post-weaning stage was accounted for by four principal components. The first factor (principal component) accounted for 38.048% (Packed cell volume), the second accounted for 24.72% (hemoglobin) and the third accounted for 19.08% (aspartate transaminase). While at the post-weaning stage, the first factor was influenced by red blood corpuscles (37.17%), the second factor had its loading for hemoglobin (25.80%), the third factor had loading for white blood corpuscles (13.67%), while the fourth factor had loading for alkaline phosphatase only (12.80%). Using communality extraction factors, ear length best described body conformation at the pre-weaning stage; whereas, at post-weaning stage, body length was the best descriptor. In blood parameters, packed cell volume best described blood marker traits at the pre-weaning stage; whereas, at the post-weaning stage, red blood corpuscles best described it. Hence, the two extracted factors in linear body measurements and in blood parameters could be considered in breeding programs to improve and predict body conformation in crossbred pigs, as well as predict blood marker traits. PMID- 26158455 TI - Regulation of Stearoyl Coenzyme A Desaturase 1 Gene Promoter in Bovine Mammary Cells. AB - Stearoyl-Coenzyme A desaturase 1 (SCD1) belongs to the fatty acid family of desaturases. In lactating ruminants, the SCD1 protein is highly expressed in the mammary gland and is relevant for the fatty acid composition of milk and dairy products. Bovine mammary epithelial cells (BME-UV1), cultured in vitro, have been proposed as a model to reproduce the biology of the mammary gland. The present study was designed to investigate the responsiveness of bovine SCD1 promoter to serum, insulin, oleic acid, and NFY transcription factor in BME-UV1 cells. A luciferase-based reporter assay was used to monitor the transcriptional activity of the SCD1 promoter region in BME-UV1 cells treated or not with insulin and/or oleic acid. The level of endogenous SCD1 mRNA was evaluated by Real time PCR. Insulin (20 ng/mL) induced a 2.0 to 2.5-fold increase of SCD1 promoter activity. Additionally, the effect of insulin was inhibited by oleic acid, serum components, and NFY enforced expression. Serum and NFY showed no synergistic or additive effect on SCD1 promoter activity suggesting that they repress SCD1 transcription through the same responsive element. PMID- 26158456 TI - Effect of Embryonic Thermal Exposure on Heat Shock Proteins (HSPs) Gene Expression and Serum T3 Concentration in Two Broiler Populations. AB - The present experiment was conducted to evaluate the Hsp-70, 27 and Ubiquitin mRNA expressions and serum T3 concentration in synthetic colored broiler female lines, Punjab Broiler-2 (PB-2), and Naked neck (NN) broiler chicken whose eggs were exposed to 2 degrees C increased incubation temperature for 3 hours each on the 16th, 17 th, and 18th day of incubation. Another set of eggs were incubated at normal conditions that were utilized as the control. A total of 432 chicks, 216 from each breed (PB-2; NN) and treatment (Heat exposed: HE; normal: N), were randomly distributed and reared at high ambient temperatures (32 degrees C-45 degrees C) during the summer season in battery brooders. Birds were sacrificed at 0 and the 28th day post hatch and different tissues (heart, liver, muscle, spleen, and bursa) were collected to study Hsps and ubiquitin mRNA expression. There was no difference between the breeds and age of slaughter in Hsp-70 mRNA expression. The Hsp(70, 27, and ubiquitin) mRNA expression was significantly (P<=0.001) lower in HE birds than that of N birds in PB-2 chickens. Nonsignificant variation was observed in NN chicken. The Hsp-70 mRNA expression was highest in bursa and lowest in muscle and liver. Serum T3 concentration was similar in both HE and N birds. The study concludes that exposure to increased temperature during incubation results in reduced expressions of Hsp mRNA in almost all tissues indicating better thermotolerance of the HE birds. PMID- 26158457 TI - Loop-Mediated Isothermal Amplification for Rapid Detection and Differentiation of Wild-Type Bovine Herpesvirus-1 and Glycoprotein E-Deleted Marker Vaccine Strain. AB - Bovine herpesvirus-1 (BoHV-1) is an important viral pathogen affecting cattle and causing numerous reproductive disorders leading to significant economic losses to the cattle industry. The control programs for BoHV-1 are widely based on the use of glycoprotein E-deleted marker vaccines, wherein detection and differentiation of wild-type and gE-deleted vaccine strains is of crucial importance for proper disease management. In this study, we report rapid and simple loop-mediated isothermal amplification (LAMP) assays for detection and differentiation of gE deleted BoHV-1 from wild-type virus under isothermal conditions. The assays could be completed in 90 mintes, including viral DNA isolation, target amplification and visual interpretation of results with naked eye. The analytical sensitivity of the assays was 10 times higher than conventional PCR and could detect as little as 100 fg of viral DNA per reaction. The applicability of LAMP for detection of BoHV-1 in bovine semen was assessed by testing semen samples collected from breeding bulls and compared with TaqMan real-time PCR (as gold standard). The LAMP assays had diagnostic specificity of 100%. The diagnostic sensitivity was 88.2% and 83.3% for gB- and gE-LAMP, respectively, when compared with TaqMan real-time PCR. Our results have shown that the LAMP method developed in this study is a potential tool for rapid, sensitive, specific, cost-effective, and user-friendly detection and differentiation of wild type BoHV-1 from gE deleted marker vaccine. PMID- 26158458 TI - Formation of an Antral Follicle-Like Structure by Bovine Cumulus-Oocyte Complexes Embedded with Fragmin/Protamine Microparticles. AB - Fragmin/protamine microparticles (F/P MPs) approximately 0.5-1 uM in diameter were prepared by the simple mixing of fragmin with protamine. This study investigated the effects of F/P MP-containing collagen gels as a hormone carrier on the formation of antral follicle-like structures and on the development of growing bovine oocytes. The supplementation of F/P MPs in collagen gels contributed to the beneficial effects of follicle stimulating hormone (FSH) on the formation and size of antral follicle-like structures. The F/P MPs may serve as potential hormone carriers for the growth of cultured bovine oocytes from early antral follicles. PMID- 26158459 TI - Nucleotide Substitution in 3' Arm of Bovine MIR-2467 in Five Cattle Breeds. AB - The T > C single nucleotide polymorphism (SNP) in the MIR2467 gene was investigated in order to confirm its presence in cattle genome and to check for possible differences in its genotype distribution among different breeds. Additional purpose of the study was to investigate in silico potential effect of that substitution on the structure and stability of precursor mir-2467. The study involved 634 individuals of five cattle breeds: Angus, Hereford, Holstein Friesian, Jersey, and Limousin, which were genotyped using PCR-RFLP assay. In this study, the presence of T > C polymorphism at position 24 was observed in all the cattle breeds excepting Hereford. In addition, the differences in the genotype distribution among analyzed breeds were indicated. On the basis of minimum free energy structure prediction, the C allele was indicated to have possible impact on decreasing the stability of the pre-mir-2467, thus altering its ability to regulate target genes expression. PMID- 26158460 TI - Construction of a CRISPR-Cas9 System for Pig Genome Targeting. AB - A Cas9/sgRNA RNA-guided endonuclease expression system including a codon optimized Streptococcus pyogenes A20 Cas9 recombinant protein expression vector and a spacer-guide chimeric RNA expression vector using the porcine U6 promoter was constructed for application in pigs. Only the Flag2-NLS1-Cas9-NLS2 recombinant protein in complex with sgRNA was translocated into the nucleus; the Flag2-NLS1-Cas9-NLS2 protein alone was excluded from the nucleus. Up to 13% of porcine PK1 cells targeted in vitro were observed, regardless of transfection efficiency. PMID- 26158461 TI - BIEC2-808543 SNP in the LCORL Gene is Associated with Body Conformation in the Yili Horse. AB - Recently, a SNP (BIEC2-808543) was demonstrated to be associated with equine body size in horses. In this study, we genotyped BIEC2-808543 SNPs in 314 Yili horses in order to evaluate the association between genotype and body composition traits, such as body weight, withers height, chest circumference, and cannon circumference. Results indicate significant associations between polymorphisms of this SNP and body conformation in Yili horse populations. Based on these results, we hypothesize that BIEC2-808543 is strongly related to body conformation of Yili horses and has the potential to be used for marker-assisted selection. PMID- 26158462 TI - Production of Cloned Wuzhishan Miniature Pigs and Application for Alloxan Toxicity Test. AB - Wuzhishan miniature pig is one of the four most important pig breeds in China and has many major economic characteristics. Herein, we successfully used SCNT to clone Wuzhishan miniature pig. First, ear fibroblasts were isolated from a 2-year old female Wuzhishan miniature piglet to be used as the donor cell. Second, good quality COCs were selected from ovaries obtained from pigs at a local slaughterhouse and cultured. Mature eggs with the first polar body and ear fibroblasts were applied SCNT. Lastly, we in total produced 12 piglets with 7 piglets surviving to adults. Next, we used these pigs to test alloxan toxicity and to build T I D diabetes type. We know that diabetes mellitus is a chronic heterogeneous metabolic disease characterized by a high blood glucose level and abnormal insulin secretion. In this study, T I D (type I diabetes) was experimentally induced in cloned Wuzhishan miniature pigs with alloxan. In brief, an intravenous injection of alloxan (group B: 170 mg/kg, n = 3) was administered to pigs weighing between 27 and 39 kg. Sterile saline was administered to control pigs (n = 3). We determined the glycometabolism related index, performed an intravenous glucose tolerance test, and carried out immunohistochemistry experiments. There were no significant differences in body weight, blood glucose, and serum insulin in all groups, before treatment. The level of blood glucose was significantly higher (P < 0.05) in group B (12.18 +/- 0.70 mmol/L) than in the control (2.93 +/- 0.39 mmol/L). By contrast, the level of serum insulin was lower in group B (5.641 +/- 0.573 MUIU/mL) than in the control (7.578 +/- 0.539 MUIU/mL). Histological studies by hematoxylin and eosin (H&E) revealed a loss of beta-cells in the pancreas from pigs treated with 170 mg/kg alloxan. Immunolocalization studies showed a decrease in insulin reactivity in this treatment group as well. To conclude, our model holds promise in future studies of diabetes drug testing and islet xenotransplantation. PMID- 26158463 TI - Lipopolysaccharide and Concanavalin A Differentially Induce the Expression of Immune Response Genes in Caprine Monocyte Derived Macrophages. AB - Monocyte derived macrophages (MDMs), as an in vitro model in pathogen challenge studies, are generally induced with lipopolysaccharide (LPS) and concanavalin A (ConA) to assay cellular immunity. General immune responses to LPS and ConA have been studied in a wide range of species, but similar studies are limited to goats. In the present study, caprine MDMs were induced with LPS and ConA and the expression profile of immune response (IR) genes, namely, Tumor Necrosis Factor Alpha (TNFA), Interferon Gamma (IFNG), Interleukin 2 (IL2), Granulocyte Macrophage Colony Stimulating Factor (GMCSF), Interleukin 10 (IL10), Transforming Growth Factor Beta (TGFB), Natural Resistance-Associated Macrophage Protein-1 (NRAMP1), inducible nitric oxide synthase (NOS2), and caspase1 (CASP1) were studied to compare the potential of LPS and ConA in initiating immune responses in goat macrophages. Real Time quantitative PCR (RT-qPCR) analysis revealed that both LPS and ConA caused an upregulation (p < 0.05) of GMCSF, TGFB1, IL10, and IFNG and down-regulation of NRAMP1. TNFA and IL2, and NOS2 were upregulated (p < 0.05) by ConA and LPS, respectively. Whereas, the expression of CASP1 remain unaltered. Comparatively, the effect of ConA was more pronounced (p < 0.05) in regulating the expression of IR genes suggesting its suitability for studying the general immune responses in caprine MDM. PMID- 26158464 TI - Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study. AB - Neuroimaging studies have shown neuromuscular electrical stimulation (NMES) evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions. PMID- 26158465 TI - An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population. AB - OBJECTIVE: Analyze the economic value of replacing conventional fetal aneuploidy screening approaches with non-invasive prenatal testing (NIPT) in the general pregnancy population. METHODS: Using decision-analysis modeling, we compared conventional screening to NIPT with cell-free DNA (cfDNA) analysis in the annual US pregnancy population. Sensitivity and specificity for fetal aneuploidies, trisomy 21, trisomy 18, trisomy 13, and monosomy X, were estimated using published data and modeling of both first- and second trimester screening. Costs were assigned for each prenatal test component and for an affected birth. The overall cost to the healthcare system considered screening costs, the number of aneuploid cases detected, invasive procedures performed, procedure-related euploid losses, and affected pregnancies averted. Sensitivity analyses evaluated the effect of variation in parameters. Costs were reported in 2014 US Dollars. RESULTS: Replacing conventional screening with NIPT would reduce healthcare costs if it can be provided for $744 or less in the general pregnancy population. The most influential variables were timing of screening entry, screening costs, and pregnancy termination rates. Of the 13,176 affected pregnancies undergoing screening, NIPT detected 96.5% (12,717/13,176) of cases, compared with 85.9% (11,314/13,176) by conventional approaches. NIPT reduced invasive procedures by 60.0%, with NIPT and conventional methods resulting in 24,596 and 61,430 invasive procedures, respectively. The number of procedure-related euploid fetal losses was reduced by 73.5% (194/264) in the general screening population. CONCLUSION: Based on our analysis, universal application of NIPT would increase fetal aneuploidy detection rates and can be economically justified. Offering this testing to all pregnant women is associated with substantial prenatal healthcare benefits. PMID- 26158466 TI - Single Turnover Autophosphorylation Cycle of the PKA RIIbeta Holoenzyme. AB - To provide tight spatiotemporal signaling control, the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme typically nucleates a macromolecular complex or a "PKA signalosome." Using the RIIbeta holoenzyme as a prototype, we show how autophosphorylation/dephosphorylation of the RIIbeta subunit, as well as cAMP and metal ions, contribute to the dynamics of PKA signaling. While we showed previously that the RIIbeta holoenzyme could undergo a single turnover autophosphorylation with adenosine triphosphate and magnesium (MgATP) and trap both products in the crystal lattice, we asked here whether calcium could trap an ATP:RIIbeta holoenzyme since the RIIbeta holoenzyme is located close to ion channels. The 2.8A structure of an RIIbetap2:C2:(Ca2ADP)2 holoenzyme, supported by biochemical and biophysical data, reveals a trapped single phosphorylation event similar to MgATP. Thus, calcium can mediate a single turnover event with either ATP or adenosine-5'-(beta,gamma-imido)triphosphate (AMP-PNP), even though it cannot support steady-state catalysis efficiently. The holoenzyme serves as a "product trap" because of the slow off-rate of the pRIIbeta subunit, which is controlled by cAMP, not by phosphorylation of the inhibitor site. By quantitatively defining the RIIbeta signaling cycle, we show that release of pRIIbeta in the presence of cAMP is reduced by calcium, whereas autophosphorylation at the phosphorylation site (P-site) inhibits holoenzyme reassociation with the catalytic subunit. Adding a single phosphoryl group to the preformed RIIbeta holoenzyme thus creates a signaling cycle in which phosphatases become an essential partner. This previously unappreciated molecular mechanism is an integral part of PKA signaling for type II holoenzymes. PMID- 26158469 TI - Spectroscopic Properties of Naphthalene on the Surface of Ice Grains Revisited: A Combined Experimental-Computational Approach. AB - An experimental-computational method is used to investigate the spectroscopic behavior of naphthalene on the surface of ice grains. UV-vis diffuse reflectance and fluorescence spectroscopies of naphthalene combined with DFT and ADC(2) calculations provide evidence for the occurrence of excited-state associates. The measured and calculated bathochromic shifts of the S0 -> S1 electronic transitions related to naphthalene dimers or naphthalene-ice interactions do not exceed 3 nm. The bands observed in the emission spectrum of frozen naphthalene solutions are assigned to excited dimers of different mutual orientations, naphthalene phosphorescence, and fluorescence of anthracene present as a trace impurity and populated by the energy transfer from excited naphthalene. Photochemical reactivity in/on ice and snow is dependent on the absorption properties and speciation of the compounds present in these media. Hence, within this study, we exploit frozen solutions of naphthalene to demonstrate both the absence of considerable bathochromic shift and a strong tendency to aggregate. PMID- 26158467 TI - The Broad Neutralizing Antibody Responses after HIV-1 Superinfection Are Not Dominated by Antibodies Directed to Epitopes Common in Single Infection. AB - HIV-1 vaccines designed to date have failed to elicit neutralizing antibodies (Nabs) that are capable of protecting against globally diverse HIV-1 subtypes. One relevant setting to study the development of a strong, cross-reactive Nab response is HIV-1 superinfection (SI), defined as sequential infections from different source partners. SI has previously been shown to lead to a broader and more potent Nab response when compared to single infection, but it is unclear whether SI also impacts epitope specificity and if the epitopes targeted after SI differ from those targeted after single infection. Here the post-SI Nab responses were examined from 21 Kenyan women collectively exposed to subtypes A, C, and D and superinfected after a median time of ~1.07 years following initial infection. Plasma samples chosen for analysis were collected at a median time point ~2.72 years post-SI. Because previous studies of singly infected populations with broad and potent Nab responses have shown that the majority of their neutralizing activity can be mapped to 4 main epitopes on the HIV-1 Envelope, we focused on these targets, which include the CD4-binding site, a V1/V2 glycan, the N332 supersite in V3, and the membrane proximal external region of gp41. Using standard epitope mapping techniques that were applied to the previous cohorts, the present study demonstrates that SI did not induce a dominant Nab response to any one of these epitopes in the 21 women. Computational sera delineation analyses also suggested that 20 of the 21 superinfected women's Nab responses could not be ascribed a single specificity with high confidence. These data are consistent with a model in which SI with diverse subtypes promotes the development of a broad polyclonal Nab response, and thus would provide support for vaccine designs using multivalent HIV immunogens to elicit a diverse repertoire of Nabs. PMID- 26158468 TI - Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli. AB - Studies of subjective well-being have conventionally relied upon self-report, which directs subjects' attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID- 26158470 TI - Predicting Toxicities of Diverse Chemical Pesticides in Multiple Avian Species Using Tree-Based QSAR Approaches for Regulatory Purposes. AB - A comprehensive safety evaluation of chemicals should require toxicity assessment in both the aquatic and terrestrial test species. Due to the application practices and nature of chemical pesticides, the avian toxicity testing is considered as an essential requirement in the risk assessment process. In this study, tree-based multispecies QSAR (quantitative-structure activity relationship) models were constructed for predicting the avian toxicity of pesticides using a set of nine descriptors derived directly from the chemical structures and following the OECD guidelines. Accordingly, the Bobwhite quail toxicity data was used to construct the QSAR models (SDT, DTF, DTB) and were externally validated using the toxicity data in four other test species (Mallard duck, Ring-necked pheasant, Japanese quail, House sparrow). Prior to the model development, the diversity in the chemical structures and end-point were verified. The external predictive power of the QSAR models was tested through rigorous validation deriving a wide series of statistical checks. Intercorrelation analysis and PCA methods provided information on the association of the molecular descriptors related to MW and topology. The S36 and MW were the most influential descriptors identified by DTF and DTB models. The DTF and DTB performed better than the SDT model and yielded a correlation (R(2)) of 0.945 and 0.966 between the measured and predicted toxicity values in test data array. Both these models also performed well in four other test species (R(2) > 0.918). ChemoTyper was used to identify the substructure alerts responsible for the avian toxicity. The results suggest for the appropriateness of the developed QSAR models to reliably predict the toxicity of pesticides in multiple avian test species and can be useful tools in screening the new chemical pesticides for regulatory purposes. PMID- 26158471 TI - Asthenopia, Associated Phoria, and Self-Selected Prism. AB - PURPOSE: The vergence position of rest (phoria) has been found to vary over time. We asked whether the vergence position of rest is correlated with discomfort on reading. METHODS: We examined 20 subjects who reported strain on prolonged reading ("asthenopes") and 20 subjects who did not ("non-asthenopes"). The eyes were normal in all subjects. Associated phoria (AP) was determined by asking the subjects to align monocular markers in the Mallett Near Vision Unit. In addition, subjects were asked to adjust Risley prisms so that viewing appeared most relaxing while they were looking at fully fusionable pictures (self-selected prism=SSP). Both AP and SSP were determined at near. Each subject participated in 6 sessions. Before each session, the subjects read a text for 30 minutes. Immediately afterwards they indicated on a visual analogue scale the discomfort they had experienced during the 30 minutes. RESULTS: In asthenopic individuals, AP fluctuated up to 19Delta, SSP up to 20Delta. In non-asthenopic individuals, AP fluctuated up to 17Delta, SSP up to 20Delta. The correlation between AP and SSP was r=0.73 (p<0.001) in the non-asthenopes and r=0.81 (p<0.001) in the asthenopes. Neither AP nor SSP were significantly larger in the asthenopes than in the non-asthenopes. Intra-individually, among the 6 sessions, the magnitude of discomfort was not significantly correlated to AP or SSP, neither in the asthenopes nor in the non-asthenopes. Asthenopes who rated their discomfort higher did not have a larger heterophoria. CONCLUSION: The lack of a significant correlation between discomfort and (horizontal) heterophoria (determined as AP or SSP), especially intra-individually among repeated measurements, does not support a causal relationship. PMID- 26158472 TI - Development of a Persian Version of the Adult Strabismus Questionnaire and Evaluating the Effect of Strabismus Surgery on Health-Related Quality of Life. AB - PURPOSE: To develop a Persian version of the Adult Strabismus Questionnaire (AS 20) and use the new questionnaire to evaluate the effect of strabismus surgery on health-related quality of life (HRQOL). METHODS: The Persian version of the AS-20 was developed with the help of Beaton and colleagues' guidelines. The reliability of the final version was tested with the test-retest and internal consistency methods. The construct and criterion (concurrent) validity were also tested for the questionnaire. Then, 112 patients with strabismus completed the questionnaire 1 week before and 3 months after strabismus surgery. RESULTS: The Persian version showed high reliability and validity. The patients with preoperative diplopia had significantly poorer median preoperative total and functional scores than the patients without preoperative diplopia (p=0.04 and 0.009, respectively). In the cases with and without diplopia, the median total, psychosocial, and functional postoperative scores were significantly better than preoperative scores (p=0.01, 0.01, and 0.028, respectively, in diplopic cases, and p<0.0001 for all scores in non-diplopic cases). The females had significantly poorer median preoperative total, psychosocial, and functional scores (p=0.001, 0.02, and 0.0001, respectively) and more postoperative total, psychosocial, and functional score improvement than males (p=0.004, 0.003, and 0.03, respectively). CONCLUSIONS: Our version might be appropriate for evaluating HRQOL of the patients with strabismus. The significant increase in the total and subscale scores after strabismus surgery showed the importance of strabismus surgery in improving HRQOL of the patients, especially in psychosocial aspects. The strabismus surgery might have a greater benefit in improving HRQOL of the female patients. PMID- 26158473 TI - Ultrasound Biomicroscopy in Strabismus Surgery: Efficacy in Postoperative Assessment of Horizontal Muscle Insertions. AB - PURPOSE: To study the efficacy of ultrasound biomicroscopy (UBM) in assessment of extraocular muscle insertion sites after strabismus surgery. METHODS: This double masked prospective interventional study included 16 eyes of 15 patients with deviation <60 prism diopters (PD) who underwent primary horizontal strabismus surgery. Preoperative muscle insertion was measured by UBM and compared with measurements done intraoperatively by surgical caliper. Both measurements by surgical caliper were taken intraoperatively before and after performing the planned repositioning of the muscle insertion. Postoperatively muscle insertion was remeasured by UBM and compared with the presumed muscle insertion after surgery. Clinically limits of agreement of +/-1 mm were taken as acceptable. RESULTS: Mean age of patients was 21+/-3 years (range 16-28 years). Preoperative average distance of the medial rectus (MR) from limbus was 5.3+/-0.3 mm (4.9-5.9 mm) by the UBM and 5.6+/-0.3 (5-6 mm) by surgical caliper (p=0.05). For lateral rectus (LR), UBM measurements from the limbus were 6.8+/-0.7 mm (5.9-8.3 mm) and 7.1+/-0.4 mm (6.5-8 mm) by calipers (p=0.067). Post-op UBM at 3 months could visualize new muscle insertion for all operated MR muscles (i.e., 100% of cases) and for LR muscles in only 50% of cases. However, accuracy could be achieved only in 78.6% of cases for MR muscle and for LR in 62.5% of cases (among LR muscles that were visible post-op). Maximum distance posterior to the limbus that the UBM was able to detect MR was 11.2 mm and for LR was 13.5 mm. CONCLUSION: UBM does not detect the new position of LR with any consistency postoperatively. Even after detection of muscle, the new insertion is only within +/-1 mm of the actual muscle insertion in 62.5% of the cases. Hence it is not a reliable tool for planning resurgery. PMID- 26158474 TI - Factors Affecting Improvement of Stereopsis Following Successful Surgical Correction of Childhood Strabismus in Adults. AB - PURPOSE: To evaluate the factors affecting improvement of stereopsis following successful surgical correction of childhood strabismus in adults. METHODS: In a prospective study, consecutive patients with childhood-onset, comitant, horizontal, constant strabismus; stereoacuity of more than 480 seconds of arc in TNO stereo test (absent stereopsis in TNO); and who had successful postoperative alignment (within 10 prism diopters [PD] of orthotropia) were enrolled. Postoperative stereopsis testing was performed using the TNO stereo test at 3 months after surgery. RESULTS: A total of 34 patients (20 exotropes and 14 esotropes) were included. The mean age at the time of surgery was 26.08+/-10.53 years (range, 14-53 years). Stereopsis was improved in 8 of 34 patients (23.5%). Postoperative alignment had influence on improvement of stereopsis; 38.1% of patients who had orthotropia gained stereopsis, whereas none of patients who had horizontal heterotropia (esotropia or exotropia) of 10 PD or less gained stereopsis (p=0.01). Misalignment of 10 years' duration or longer did not preclude the development of postoperative stereoacuity (p=0.31). There was a statistically insignificant increase in improvement of stereopsis in nonamblyopic group (30.4%) compared with amblyopic group (9.1%) (p=0.22). Also, there was a statistically insignificant increase in improvement of stereopsis in exotropes (35%) compared with esotropes (7.1%) (p=0.1). The angle of preoperative deviation had no influence on improvement of stereopsis (p=0.44). CONCLUSION: A postoperative correction of orthotropia was the only predictive factor for improvement of stereopsis in adults with childhood strabismus. PMID- 26158475 TI - The Mechanism Underlying the Bruckner Effect Studied with an Automated, High Resolution, Continuously Scanning Bruckner Device. AB - INTRODUCTION: When an eye is illuminated by a light coaxial with the observing eye or camera, the light is reflected by the back of the eye and a red reflex will be observed through the pupil. The intensity of this red reflex varies with the angle of eccentric gaze. The red reflex darkens as the eye fixates at the light source. Bruckner described this principle in 1962. Although this effect has been used as a screening test for strabismus ever since, the mechanism that causes this effect is only partly known. None of the current explanations are accepted as conclusively proven. We developed an automated, high-resolution, continuously scanning Bruckner device to study the mechanisms underlying the Bruckner effect. METHOD: The right eyes of 6 subjects, students aged 22-31 years, were measured. A subject sat in front of a camera at a distance of about 0.75 m. The luminance of the red fundus reflex and the eye movements were measured continuously while the subject followed a fixation target that moved in two dimensions. Eye movement was also recorded objectively and in the analysis this was used in addition to the position of the fixation target. The eyes were illuminated coaxially using an infrared light source and a beam splitter. RESULT: By using two methods to record eye rotation and relating this to the continuously measured pupillary luminous intensity and pupillary area, we were able to construct 2-dimensional maps of pupillary luminance. All 6 subjects showed the expected general darkening of the pupil as fixation changed from eccentric fixation to foveal fixation at the center of the camera. However, there were many local fluctuations. The global minimum in pupillary luminance, the "dark spot," was often roughly circle-shaped with a radius of about 1 degrees . The pupillary luminance kept increasing beyond 2 degrees eccentricity. DISCUSSION: We measured the Bruckner effect continuously in two dimensions. Bruckner's original explanation--absorption by the macular pigment--cannot explain our findings as the macular pigment hardly absorbs light beyond 600 nm wavelength. If one assumes that reflection by the inner limiting membrane or diffuse backscatter in the thick retinal nerve fiber layer increase the luminance of the pupil, one would expect the pupil to be brightest at 2 degrees eccentricity, but the pupillary luminance continued to increase beyond that. We used a beam splitter and still found a dark pupil on coaxial fixation, implying that blocking the image that is projected back from the eye by the funduscope only plays a contributory role. PMID- 26158476 TI - The Physiologist Ewald Hering (1834-1918): Curriculum vitae. PMID- 26158477 TI - Expedient Access to Unsymmetrical Diarylindolylmethanes through Palladium Catalyzed Domino Electrophilic Cyclization-Extended Conjugate Addition Approach. AB - A palladium-catalyzed domino process to access unsymmetrical diarylindolylmethanes has been developed through the annulation of o alkynylanilines followed by 1,6-conjugate addition with p-quinone methides (p QMs) under relatively mild conditions. The broad substrate scope of this methodology was demonstrated through the use of a wide range of substituted o alkynylanilines and p-quinone methides, and in most cases, the unsymmetrical diarylindolylmethanes could be prepared in moderate to excellent yields. Notably, this method does not require any amino group protection. Moreover, 100% atom economy makes this transformation attractive from a green chemistry perspective. PMID- 26158478 TI - What Differences Make a Difference? The Promise and Reality of Diverse Teams in Organizations. AB - -As the workplace has become increasingly diverse, there has been a tension between the promise and the reality of diversity in team process and performance. The optimistic view holds that diversity will lead to an increase in the variety of perspectives and approaches brought to a problem and to opportunities for knowledge sharing, and hence lead to greater creativity and quality of team performance. However, the preponderance of the evidence favors a more pessimistic view: that diversity creates social divisions, which in turn create negative performance outcomes for the group. Why is the reality of diversity less than the promise? Answering this requires understanding a variety of factors, including how diversity is defined and categorized, and the moderating as well as mediating processes that affect the diversity-process-performance linkage. We start with a definition. The word diversity has been used to refer to so many types of differences among people that the most commonly used definition-"any attribute that another person may use to detect individual differences" (Williams & O'Reilly, 1998, p. 81)-while accurate, is also quite broad. As a result, various categorization schemes based on factors such as race or gender, or based on proportions such as the size of the minority, have been used to further refine the definition of diversity in teams. The choices researchers have made in using these categorization schemes, however, do lead to particular tradeoffs. Factor approaches, for example, allow an examination of multiple types of diversity and the interactions among them but ignore the sizes of factions and subgroups. Proportional approaches allow the consideration of minority-group size, and hence the study of issues such as tokenism, but also tend to focus on only one type of diversity and thereby overestimate its relevance relative to other types. The underlying effects of diversity, whichever way it is defined and categorized, have typically been understood through three primary theoretical perspectives: the similarity-attraction paradigm, self- and social categorization, and information processing. These approaches also have their biases. The predictions of similarity-attraction theory are straightforward: Similarity on attributes such as attitudes, values, and beliefs will facilitate interpersonal attraction and liking. Empirical research has supported that surface-level similarity tends to predict affiliation and attraction. The similarity-attraction paradigm was developed to understand dyadic relationships. Yet, individuals can express preferences for membership in particular groups even when they have had no prior social interaction with members of that group. This is primarily a cognitive process of categorization: Individuals are postulated to have a hierarchical structure of self-categorizations at the personal, group, and superordinate levels. Research has demonstrated that the specific categories on which we tend to focus in categorizing others-such as race, gender, values, or beliefs-are likely to be those that are the most distinctive or salient within the particular social context. The act of social categorization activates differential expectations for in-group and out-group members. This distinction creates the atmosphere for stereotyping, in which out-group members are judged more stereotypically than in-group members are. The self-categorization/social identity and similarity-attraction approaches both tend to lead to the pessimistic view of diversity in teams. In these paradigms, individuals will be more attracted to similar others and will experience more cohesion and social integration in homogeneous groups. The information-processing approach, by contrast, offers a more optimistic view: that diversity creates an atmosphere for enhancing group performance. The information-processing approach argues that individuals in diverse groups have access to other individuals with different backgrounds, networks, information, and skills. This added information should improve the group outcome even though it might create coordination problems for the group. As we disentangle what researchers have learned from the last 50 years, we can conclude that surface-level social- category differences, such as those of race/ethnicity, gender, or age, tend to be more likely to have negative effects on the ability of groups to function effectively. By contrast, underlying differences, such as differences in functional background, education, or personality, are more often positively related to performance-for example by facilitating creativity or group problem solving-but only when the group process is carefully controlled. The majority of these effects have typically been explained in terms of potential mediators such as social integration, communication, and conflict. However, the actual evidence for the input-process output linkage is not as strong as one might like. Clarifying the mixed effects of diversity in work groups will only be possible by carefully considering moderators such as context, by broadening our view to include new types of diversity such as emotions and networks, and by focusing more carefully on mediating mechanisms. As we delve into advice for organizational teams to enhance the assets of diversity and manage the liabilities, we focus on the benefits of "exploring" as opposed to "exploiting" types of tasks, of bridging diversity through values and goals, and of enhancing the power of the minority. Finally, we end with suggestions for how organizations can learn to create incentives for change within the firm. PMID- 26158479 TI - Diversity in Teams: A Two-Edged Sword Requires Careful Handling. PMID- 26158480 TI - Spatial distribution of electrical conductivity and stable isotopes in groundwater in large catchments: a geostatistical approach in the Quequen Grande River catchment, Argentina. AB - Stable isotopes and electrical conductivity in groundwater were used as natural tracers to adjust the hydrogeological conceptual model in one of the largest catchments within the inter-mountainous Pampa plain, Argentina. Geostatistical tools were used to define the model that best fitted the spatial distribution of each tracer, and information was obtained in areas where there was a lack of data. The conventional isotopic analysis allowed the identification of three groundwater groups with different isotopic fingerprints. One group containing 56% of the total groundwater samples suggested a well-mixed system and soil infiltration precipitation as the main recharge source to the aquifer. The other two groups included samples with depleted (25.5%) and enriched (18.5%) isotopic compositions, respectively. The combination of delta(18)O, delta(2)H and electrical conductivities maps suggested ascending regional flows and water transfer from the Quequen Grande River catchment to the Moro creek. The spatial interpretation of these tracers modified the conceptual hydrogeological model of the Quequen Grande River. PMID- 26158484 TI - Raindrop impact on sand: a dynamic explanation of crater morphologies. AB - As a droplet impacts upon a granular substrate, both the intruder and the target undergo deformation, during which the liquid may penetrate into the substrate. These three aspects together distinguish it from other impact phenomena in the literature. We perform high-speed, double-laser profilometry measurements and disentangle the dynamics into three aspects: the deformation of the substrate during the impact, the maximum spreading diameter of the droplet, and the penetration of the liquid into the substrate. By systematically varying the impact speed and the packing fraction of the substrate, (i) the substrate deformation indicates a critical packing fraction phi* ~ 0.585; (ii) the maximum droplet spreading diameter is found to scale with a Weber number corrected by the substrate deformation; and (iii) a model of the liquid penetration is established and is used to explain the observed crater morphology transition. PMID- 26158485 TI - Toward a realistic optoelectronic-based kinematic model of the hand: representing the transverse metacarpal arch reduces accessory rotations of the metacarpophalangeal joints. AB - A kinematic model representing the versatility of the human hand is needed to evaluate biomechanical function and predict injury risk in the workplace. We improved upon an existing optoelectronic-based kinematic hand model with grouped metacarpals by defining segmented metacarpals and adding the trapeziometacarpal joint of the thumb. Eight participants performed three static postures (neutral pose, cylinder grip, cap grip) to evaluate kinematic performance of three different models, with one, two, and four metacarpal segment(s). Mean distal transverse metacarpal arch angles in the four-segment metacarpal model were between 22.0 degrees +/- 3.3 degrees (neutral pose) and 32.1 degrees +/- 3.7 degrees (cap grip). Representation of the metacarpals greatly influenced metacarpophalangeal joint rotations. Both the two- and four-segment metacarpal models displayed significantly lower metacarpophalangeal joint 'supination' angles (than the one-segment model) for the fourth and fifth fingers. However, the largest reductions were for the four- versus one-segment models, with mean differences ranging from 9.3 degrees (neutral pose) to 17.0 degrees (cap grip) for the fourth finger and 16.3 degrees (neutral pose) to 33.0 degrees (cylinder grip) for the fifth finger. MCP joint abduction/adduction angles of the fourth and fifth fingers also decreased with segmentation of the metacarpals, although the lowest magnitudes generally occurred in the four-segment model. Overall, the four-segment metacarpal model produced the lowest accessory rotations in non dominant axes, and best matched previous radiological studies that found MCP joint pronation/supination angles were typically less than 10 degrees . The four segment metacarpal model, with improved anatomic fidelity, will better serve future studies of detailed actions of the hand in clinical or work applications. PMID- 26158487 TI - A Copper-Catalyzed Formal [3 + 2]-Cycloaddition for the Synthesis of All Different Aryl-Substituted Furans and Thiophenes. AB - A highly efficient formal [3 + 2]-cycloaddition was established using a copper catalyst. The resulting dihydrofurans were subjected to oxidation followed by arylations to produce tetraarylfurans. In addition, the dihydrofuran can be converted to diaryldihydrothiophene by using Lawesson's reagent. This protocol will facilitate the synthesis of all different aryl-substituted furans and thiophenes. PMID- 26158488 TI - Enrichment and Analysis of Intact Phosphoproteins in Arabidopsis Seedlings. AB - Protein phosphorylation regulates diverse cellular functions and plays a key role in the early development of plants. To complement and expand upon previous investigations of protein phosphorylation in Arabidopsis seedlings we used an alternative approach that combines protein extraction under non-denaturing conditions with immobilized metal-ion affinity chromatography (IMAC) enrichment of intact phosphoproteins in Rubisco-depleted extracts, followed by identification using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In-gel trypsin digestion and analysis of selected gel spots identified 144 phosphorylated peptides and residues, of which only 18 phosphopeptides and 8 phosphosites were found in the PhosPhAt 4.0 and P3DB Arabidopsis thaliana phosphorylation site databases. More than half of the 82 identified phosphoproteins were involved in carbohydrate metabolism, photosynthesis/respiration or oxidative stress response mechanisms. Enrichment of intact phosphoproteins prior to 2-DE and LC-MS/MS appears to enhance detection of phosphorylated threonine and tyrosine residues compared with methods that utilize peptide-level enrichment, suggesting that the two approaches are somewhat complementary in terms of phosphorylation site coverage. Comparing results for young seedlings with those obtained previously for mature Arabidopsis leaves identified five proteins that are differentially phosphorylated in these tissues, demonstrating the potential of this technique for investigating the dynamics of protein phosphorylation during plant development. PMID- 26158489 TI - Emission and Dispersion of Bioaerosols from Dairy Manure Application Sites: Human Health Risk Assessment. AB - In this study, we report the human health risk of gastrointestinal infection associated with inhalation exposure to airborne zoonotic pathogens emitted following application of dairy cattle manure to land. Inverse dispersion modeling with the USEPA's AERMOD dispersion model was used to determine bioaerosol emission rates based on edge-of-field bioaerosol and source material samples analyzed by real-time quantitative polymerase chain reaction (qPCR). Bioaerosol emissions and transport simulated with AERMOD, previously reported viable manure pathogen contents, relevant exposure pathways, and pathogen-specific dose response relationships were then used to estimate potential downwind risks with a quantitative microbial risk assessment (QMRA) approach. Median 8-h infection risks decreased exponentially with distance from a median of 1:2700 at edge-of field to 1:13 000 at 100 m and 1:200 000 at 1000 m; peak risks were considerably greater (1:33, 1:170, and 1:2500, respectively). These results indicate that bioaerosols emitted from manure application sites following manure application may present significant public health risks to downwind receptors. Manure management practices should consider improved controls for bioaerosols in order to reduce the risk of disease transmission. PMID- 26158490 TI - Tuning the formation of discrete coordination nanostructures. AB - Novel surface coordination nanostructures based on cyanosexiphenyl molecules are assembled on a gold surface and investigated by scanning tunneling microscopy and density functional theory. Their formation can be tuned by varying the surface temperature during deposition. Diffusing gold adatoms act as coordination centers for the cyano groups present on one end of the nonsymmetrical molecules. PMID- 26158491 TI - The role of lexical expertise in reading homophones. AB - In Experiment 1, university students classified on lexical expertise on the basis of spelling plus nonword pronunciation accuracy made lexical decisions to homophones and control words. Homophones were accepted as words more slowly than control words, but lexical experts showed a smaller homophone cost than the less skilled group. In Experiment 2, similarly classified groups showed a large difference in their ability to detect homophones, with the low-expertise group showing a yes bias to high-frequency words, and having difficulty detecting homophones when mate-frequency was low. The results suggest superior use of orthography in the lexical experts and more reliance on semantic information in nonexperts, and support the importance of facility with orthography-phonology mappings in lexical expertise. PMID- 26158494 TI - Grassland Arthropods Are Controlled by Direct and Indirect Interactions with Cattle but Are Largely Unaffected by Plant Provenance. AB - Cattle grazing and invasion by non-native plant species are globally-ubiquitous changes occurring to plant communities that are likely to reverberate through whole food webs. We used a manipulative field experiment to quantify how arthropod community structure differed in native and non-native California grassland communities in the presence and absence of grazing. The arthropod community was strongly affected by cattle grazing: the biovolume of herbivorous arthropods was 79% higher in grazed than ungrazed plots, whereas the biovolume of predatory arthropods was 13% higher in ungrazed plots. In plots where non-native grasses were grazed, arthropod biovolume increased, possibly in response to increased plant productivity or increased nutritional quality of rapidly-growing annual plants. Grazing may thus affect plant biomass both through the direct removal of biomass, and through arthropod-mediated impacts. We also expected the arthropod community to differ between native and non-native plant communities; surprisingly, arthropod richness and diversity did not vary consistently between these grass community types, although arthropod abundance was slightly higher in plots with native and ungrazed grasses. These results suggest that whereas cattle grazing affects the arthropod community via direct and indirect pathways, arthropod community changes commonly associated with non-native plant invasions may not be due to the identity or dominance of the invasive species in those systems, but to accompanying changes in plant traits or functional group composition, not seen in this experiment because of the similarity of the plant communities. PMID- 26158495 TI - Tuning Surface Charge and PEGylation of Biocompatible Polymers for Efficient Delivery of Nucleic Acid or Adenoviral Vector. AB - As an effective and safe strategy to overcome the limits of therapeutic nucleic acid or adenovirus (Ad) vectors for in vivo application, various technologies to modify the surface of vectors with nonimmunogenic/biocompatible polymers have been emerging in the field of gene therapy. However, the transfection efficacy of the polymer to transfer genetic materials is still relatively weak. To develop more advanced and effective polymers to deliver not only Ad vectors, but also nucleic acids, 6 biocompatible polymers were newly designed and synthesized to different sizes (2k, 3.4k, or 5k) of poly(ethylene) glycol (PEG) and different numbers of amine groups (2 or 5) based on methoxy poly(ethylene glycol)-b-poly{N [N-(2-aminoethyl)-2-aminoethyl]-l-glutamate (PNLG). We characterized size distribution and surface charge of 6 PNLGs after complexation with either nucleic acid or Ad. Among all 6 PNLGs, the 5 amine group PNLG showed the strongest efficacy in delivering nucleic acid as well as Ad vectors. Interestingly, cellular uptake results showed higher uptake ability in Ad complexed with 2 amine group PNLG than Ad/5 amine group PNLG, suggesting that the size of Ad/PNLGs is more essential than the surface charge for cellular uptake in polymers with charges greater than 30 mV. Moreover, the endosome escape ability of Ad/PNLGs increased depending on the number of amine groups, but decreased by PEG size. Cancer cell killing efficacy and immune response studies of oncolytic Ad/PNLGs showed 5 amine group PNLG to be a more effective and safe carrier for delivering Ad. Overall, these studies provide new insights into the functional mechanism of polymer-based approaches to either nucleic acid or Ad/nanocomplex. Furthermore, the identified ideal biocompatible PNLG polymer formulation (5 amine/2k PEG for nucleic acid, 5 amine/5k PEG for Ad) demonstrated high transduction efficiency as well as therapeutic value (efficacy and safety) and thus has strong potential for in vivo therapeutic use in the future. PMID- 26158498 TI - How Co-translational Folding of Multi-domain Protein Is Affected by Elongation Schedule: Molecular Simulations. AB - Co-translational folding (CTF) facilitates correct folding in vivo, but its precise mechanism remains elusive. For the CTF of a three-domain protein SufI, it was reported that the translational attenuation is obligatory to acquire the functional state. Here, to gain structural insights on the underlying mechanisms, we performed comparative molecular simulations of SufI that mimic CTF as well as refolding schemes. A CTF scheme that relied on a codon-based prediction of translational rates exhibited folding probability markedly higher than that by the refolding scheme. When the CTF schedule is speeded up, the success rate dropped. These agree with experiments. Structural investigation clarified that misfolding of the middle domain was much more frequent in the refolding scheme than that in the codon-based CTF scheme. The middle domain is less stable and can fold via interactions with the folded N-terminal domain. Folding pathway networks showed the codon-based CTF gives narrower pathways to the native state than the refolding scheme. PMID- 26158499 TI - Data Mining of Determinants of Intrauterine Growth Retardation Revisited Using Novel Algorithms Generating Semantic Maps and Prototypical Discriminating Variable Profiles. AB - OBJECTIVES: Intra-uterine growth retardation is often of unknown origin, and is of great interest as a "Fetal Origin of Adult Disease" has been now well recognized. We built a benchmark based upon a previously analysed data set related to Intrauterine Growth Retardation with 46 subjects described by 14 variables, related with the insulin-like growth factor system and pro inflammatory cytokines, namely interleukin-6 and tumor necrosis factor-alpha. DESIGN AND METHODS: We used new algorithms for optimal information sorting based on the combination of two neural network algorithms: Auto-contractive Map and Activation and Competition System. Auto-Contractive Map spatializes the relationships among variables or records by constructing a suitable embedding space where 'closeness' among variables or records reflects accurately their associations. The Activation and Competition System algorithm instead works as a dynamic non linear associative memory on the weight matrices of other algorithms, and is able to produce a prototypical variable profile of a given target. RESULTS: Classical statistical analysis, proved to be unable to distinguish intrauterine growth retardation from appropriate-for-gestational age (AGA) subjects due to the high non-linearity of underlying functions. Auto-contractive map succeeded in clustering and differentiating completely the conditions under study, while Activation and Competition System allowed to develop the profile of variables which discriminated the two conditions under study better than any other previous form of attempt. In particular, Activation and Competition System showed that ppropriateness for gestational age was explained by IGF-2 relative gene expression, and by IGFBP-2 and TNF-alpha placental contents. IUGR instead was explained by IGF-I, IGFBP-1, IGFBP-2 and IL-6 gene expression in placenta. CONCLUSION: This further analysis provided further insight into the placental key players of fetal growth within the insulin-like growth factor and cytokine systems. Our previous published analysis could identify only which variables were predictive of fetal growth in general, and identified only some relationships. PMID- 26158500 TI - A microengineered pathophysiological model of early-stage breast cancer. AB - A mounting body of evidence in cancer research suggests that the local microenvironment of tumor cells has a profound influence on cancer progression and metastasis. In vitro studies on the tumor microenvironment and its pharmacological modulation, however, are often hampered by the technical challenges associated with creating physiological cell culture environments that integrate cancer cells with the key components of their native niche such as neighboring cells and extracellular matrix (ECM) to mimic complex microarchitecture of cancerous tissue. Using early-stage breast cancer as a model disease, here we describe a biomimetic microengineering strategy to reconstitute three-dimensional (3D) structural organization and microenvironment of breast tumors in human cell-based in vitro models. Specifically, we developed a microsystem that enabled co-culture of breast tumor spheroids with human mammary ductal epithelial cells and mammary fibroblasts in a compartmentalized 3D microfluidic device to replicate microarchitecture of breast ductal carcinoma in situ (DCIS). We also explored the potential of this breast cancer-on-a-chip system as a drug screening platform by evaluating the efficacy and toxicity of an anticancer drug (paclitaxel). Our microengineered disease model represents the first critical step towards recapitulating pathophysiological complexity of breast cancer, and may serve as an enabling tool to systematically examine the contribution of the breast cancer microenvironment to the progression of DCIS to an invasive form of the disease. PMID- 26158501 TI - Neuroprotective actions of progesterone in an in vivo model of retinitis pigmentosa. AB - Progesterone has been shown to have neuroprotective effects in experimental acute brain injury models, but little is known about the effects of steroid sex hormones in models of retinitis pigmentosa (RP). The aim of this study was to asses whether progesterone had a protective effect in one animal model of RP (the rd1 mice), and whether its action was due at least in part, to its ability to reduce free radical damage or to increase antioxidant defences. Rd1 and wild type (wt) mice received an oral administration of 100 mg/kg body/weight of progesterone on alternate days starting at postnatal day 7 (PN7) and were sacrificed at different postnatal days. Our results show that progesterone decreases cell death, as the number of TUNEL-positive cells were decreased in the ONL of the retina from treated rd1 mice. At PN15, treatment with progesterone increased values of ERG b-wave amplitude (p<0,5) when compared with untreated mice. Progesterone also decreased the observed gliosis in RP, though this effect was transient. Treatment with progesterone significantly reduced retinal glutamate concentrations at PN15 and PN17. To clarify the mechanism by which progesterone is able to decrease retinal glutamate concentration, we examined expression levels of glutamine synthase (GS). Our results showed a significant increase in GS in rd1 treated retinas at PN13. Treatment with progesterone, significantly increase not only GSH but also oxidized glutathione retinal concentrations, probably because progesterone is able to partially increase glutamate cysteine ligase c subunit (GCLC) at PN15 and PN17 (p<0,05). In summary, our results demonstrate that oral administration of progesterone appears to act on multiple levels to delay photoreceptor death in this model of RP. PMID- 26158503 TI - Quantitative comparison of OSEM and penalized likelihood image reconstruction using relative difference penalties for clinical PET. AB - Ordered subset expectation maximization (OSEM) is the most widely used algorithm for clinical PET image reconstruction. OSEM is usually stopped early and post filtered to control image noise and does not necessarily achieve optimal quantitation accuracy. As an alternative to OSEM, we have recently implemented a penalized likelihood (PL) image reconstruction algorithm for clinical PET using the relative difference penalty with the aim of improving quantitation accuracy without compromising visual image quality. Preliminary clinical studies have demonstrated visual image quality including lesion conspicuity in images reconstructed by the PL algorithm is better than or at least as good as that in OSEM images. In this paper we evaluate lesion quantitation accuracy of the PL algorithm with the relative difference penalty compared to OSEM by using various data sets including phantom data acquired with an anthropomorphic torso phantom, an extended oval phantom and the NEMA image quality phantom; clinical data; and hybrid clinical data generated by adding simulated lesion data to clinical data. We focus on mean standardized uptake values and compare them for PL and OSEM using both time-of-flight (TOF) and non-TOF data. The results demonstrate improvements of PL in lesion quantitation accuracy compared to OSEM with a particular improvement in cold background regions such as lungs. PMID- 26158505 TI - Capturing the signal. AB - High-resolution structures provide new insights into how an RNA-protein complex recognizes the signal that targets membrane proteins to the endoplasmic reticulum before they aggregate. PMID- 26158502 TI - Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses. AB - It is well accepted that ethanol is able to produce major health and economic problems associated to its abuse. Because of its intoxicating and addictive properties, it is necessary to analyze its effect in the central nervous system. However, we are only now learning about the mechanisms controlling the modification of important membrane proteins such as ligand-activated ion channels by ethanol. Furthermore, only recently are these effects being correlated to behavioral changes. Current studies show that the glycine receptor (GlyR) is a susceptible target for low concentrations of ethanol (5-40mM). GlyRs are relevant for the effects of ethanol because they are found in the spinal cord and brain stem where they primarily express the alpha1 subunit. More recently, the presence of GlyRs was described in higher regions, such as the hippocampus and nucleus accumbens, with a prevalence of alpha2/alpha3 subunits. Here, we review data on the following aspects of ethanol effects on GlyRs: (1) direct interaction of ethanol with amino acids in the extracellular or transmembrane domains, and indirect mechanisms through the activation of signal transduction pathways; (2) analysis of alpha2 and alpha3 subunits having different sensitivities to ethanol which allows the identification of structural requirements for ethanol modulation present in the intracellular domain and C-terminal region; (3) Genetically modified knock-in mice for alpha1 GlyRs that have an impaired interaction with G protein and demonstrate reduced ethanol sensitivity without changes in glycinergic transmission; and (4) GlyRs as potential therapeutic targets. PMID- 26158506 TI - Structure and functional properties of Norrin mimic Wnt for signalling with Frizzled4, Lrp5/6, and proteoglycan. AB - Wnt signalling regulates multiple processes including angiogenesis, inflammation, and tumorigenesis. Norrin (Norrie Disease Protein) is a cystine-knot like growth factor. Although unrelated to Wnt, Norrin activates the Wnt/beta-catenin pathway. Signal complex formation involves Frizzled4 (Fz4), low-density lipoprotein receptor related protein 5/6 (Lrp5/6), Tetraspanin-12 and glycosaminoglycans (GAGs). Here, we report crystallographic and small-angle X-ray scattering analyses of Norrin in complex with Fz4 cysteine-rich domain (Fz4CRD), of this complex bound with GAG analogues, and of unliganded Norrin and Fz4CRD. Our structural, biophysical and cellular data, map Fz4 and putative Lrp5/6 binding sites to distinct patches on Norrin, and reveal a GAG binding site spanning Norrin and Fz4CRD. These results explain numerous disease-associated mutations. Comparison with the Xenopus Wnt8-mouse Fz8CRD complex reveals Norrin mimics Wnt for Frizzled recognition. The production and characterization of wild-type and mutant Norrins reported here open new avenues for the development of therapeutics to combat abnormal Norrin/Wnt signalling. PMID- 26158508 TI - Microscopic Investigations into the Effect of Surface Treatment of Cathode and Electron Transport Layer on the Performance of Inverted Organic Solar Cells. AB - Surface treatments of various layers in organic solar cells play a vital role in determining device characteristics. In this manuscript, we report on the influence of surface treatment of indium tin oxide (ITO) electrode and electron transport layer (ETL), ZnO, on the photovoltaic performance of inverted organic solar cells (IOSC) and their correlation with the surface chemistry and surface potential as studied using X-ray photoelectron spectroscopy (XPS) and Kelvin probe force microscopy (KPFM), using the device structure glass/ITO/ZnO/P3HT: PCBM/MoO3/(Au or Ag) (P3HT, poly(3-hexylthiophene-2,5-diyl), and PCBM, phenyl-C61 butyric acid methyl ester). Our results show that although ozonization of ITO leads to an improvement in the device power conversion efficiency, the ozonization of a subsequent ZnO layer results in a decreased performance mainly because of a decrease in the fill factor (FF). However, subsequent methanol (CH3OH) treatment of ZnO layer on an ozonized ITO electrode shows substantial improvement with device efficiencies exceeding ~4% along with superior reproducibility of the devices. Furthermore, a detailed analysis of the surface wettability, chemistry, and surface potential using contact angle measurements, XPS, and KPFM attribute the improvements to the elimination of surface defects and the changes in the surface potential. Finally, impedance analysis suggests that methanol treatment of the ZnO layers leads to the development of a favorable nanophase structure with higher conductivity, which is otherwise indiscernible using microscopic methods. PMID- 26158507 TI - Structures of the scanning and engaged states of the mammalian SRP-ribosome complex. AB - The universally conserved signal recognition particle (SRP) is essential for the biogenesis of most integral membrane proteins. SRP scans the nascent chains of translating ribosomes, preferentially engaging those with hydrophobic targeting signals, and delivers these ribosome-nascent chain complexes to the membrane. Here, we present structures of native mammalian SRP-ribosome complexes in the scanning and engaged states. These structures reveal the near-identical SRP architecture of these two states, show many of the SRP-ribosome interactions at atomic resolution, and suggest how the polypeptide-binding M domain selectively engages hydrophobic signals. The scanning M domain, pre-positioned at the ribosomal exit tunnel, is auto-inhibited by a C-terminal amphipathic helix occluding its hydrophobic binding groove. Upon engagement, the hydrophobic targeting signal displaces this amphipathic helix, which then acts as a protective lid over the signal. Biochemical experiments suggest how scanning and engagement are coordinated with translation elongation to minimize exposure of hydrophobic signals during membrane targeting. PMID- 26158509 TI - Biotin starvation causes mitochondrial protein hyperacetylation and partial rescue by the SIRT3-like deacetylase Hst4p. AB - The essential vitamin biotin is a covalent and tenaciously attached prosthetic group in several carboxylases that play important roles in the regulation of energy metabolism. Here we describe increased acetyl-CoA levels and mitochondrial hyperacetylation as downstream metabolic effects of biotin deficiency. Upregulated mitochondrial acetylation sites correlate with the cellular deficiency of the Hst4p deacetylase, and a biotin-starvation-induced accumulation of Hst4p in mitochondria supports a role for Hst4p in lowering mitochondrial acetylation. We show that biotin starvation and knockout of Hst4p cause alterations in cellular respiration and an increase in reactive oxygen species (ROS). These results suggest that Hst4p plays a pivotal role in biotin metabolism and cellular energy homeostasis, and supports that Hst4p is a functional yeast homologue of the sirtuin deacetylase SIRT3. With biotin deficiency being involved in various metabolic disorders, this study provides valuable insight into the metabolic effects biotin exerts on eukaryotic cells. PMID- 26158510 TI - Atrial Fibrillation Is Associated with a Marker of Endothelial Function and Oxidative Stress in Patients with Acute Myocardial Infarction. AB - BACKGROUND: Atrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI. METHODS: 273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) >=48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample. RESULTS: The incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly older than patients without AF (~ 20 y). There was a trend towards higher ADMA levels in patients with symptomatic AF than in patients with silent AF or no AF (0.53 vs 0.49 and 0.49 MUmol/L, respectively, p = 0.18,). After matching on age, we found that patients with symptomatic AF had a higher heart rate on admission and a higher rate of patients with LV dysfunction (28% vs. 3%, p = 0.025). Patients who developed symptomatic AF had a higher ADMA level than patients without AF (0.53 vs. 0.43 MUmol/L; p = 0.001). Multivariate logistic regression analysis to estimate symptomatic AF occurrence showed that ADMA was independently associated with symptomatic AF (OR: 2.46 [1.21-5.00], p = 0.013) beyond history of AF, LVEF<40% and elevated HR. CONCLUSION: We show that high ADMA level is associated with the occurrence of AF. Although no causative role can be concluded from our observational study, our work further supports the hypothesis that endothelial dysfunction is involved in the pathogenesis of AF in AMI. PMID- 26158511 TI - Special issue on South Asian mental health. PMID- 26158512 TI - Multiple sclerosis: getting personal with induced pluripotent stem cells. AB - Human induced pluripotent stem (iPS) cells can be derived from lineage-restricted cells and represent an important tool to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. Recently, patient-derived iPS cells, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. By offering an unlimited source of patient-specific disease-relevant cells, iPS cells hold great promise for understanding disease mechanisms, identifying molecular targets and developing phenotypic screens for drug discovery. This review will discuss the potential impact of using iPS cell-derived models in multiple sclerosis (MS) research and highlight some of the current challenges and prospective for generating novel therapeutic treatments for MS patients. PMID- 26158513 TI - Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents. AB - Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-kappaB (NF-kappaB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8 activating enzyme (NAE), abrogates stromal-mediated NF-kappaB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-kappaB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents. PMID- 26158514 TI - miR-612 negatively regulates colorectal cancer growth and metastasis by targeting AKT2. AB - Colorectal cancer (CRC) is one of the most common cancers worldwide, with a particularly high incidence in developed countries. Distant metastasis and recurrence are the main causes of CRC-related deaths. MicroRNAs (miRNAs) in the serum make them potential biomarkers for cancers, as reported in serum or tumor tissues from CRC patients. In this study, we found that miR-612 expression was significantly lower in CRC tissues or cells compared with peritumor tissues or normal cells, and lower in metastatic CRC specimens compared with non-metastatic specimens, whereas AKT2 exhibited opposite trend. Gain-of-function and loss-of function assays showed that miR-612 inhibited CRC cell proliferation and migration in vitro by Cell Counting Kit-8 and transwell assays. Further analysis revealed that miR-612 directly suppressed AKT2, which in turn inhibited the downstream epithelial-mesenchymal transition-related signaling pathway. These results were additionally validated in vivo by tumorigenesis and liver metastasis experiments. The results of this study suggested a critical role of miR-612 in the development of CRC. PMID- 26158515 TI - Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction. AB - The BH3-only protein Bim is a potent direct activator of the proapoptotic effector protein Bax, but the structural basis for its activity has remained poorly defined. Here we describe the crystal structure of the BimBH3 peptide bound to BaxDeltaC26 and structure-based mutagenesis studies. Similar to BidBH3, the BimBH3 peptide binds into the cognate surface groove of Bax using the conserved hydrophobic BH3 residues h1-h4. However, the structure and mutagenesis data show that Bim is less reliant compared with Bid on its 'h0' residues for activating Bax and that a single amino-acid difference between Bim and Bid encodes a fivefold difference in Bax-binding potency. Similar to the structures of BidBH3 and BaxBH3 bound to BaxDeltaC21, the structure of the BimBH3 complex with BaxDeltaC displays a cavity surrounded by Bax alpha1, alpha2, alpha5 and alpha8. Our results are consistent with a model in which binding of an activator BH3 domain to the Bax groove initiates separation of its core (alpha2-alpha5) and latch (alpha6-alpha8) domains, enabling its subsequent dimerisation and the permeabilisation of the mitochondrial outer membrane. PMID- 26158516 TI - First MCL-1-selective BH3 mimetics as potential therapeutics for targeted treatment of cancer. PMID- 26158517 TI - Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons. AB - Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals and axons precedes the demise of dopaminergic neurons in the substantia nigra, which finally results in the clinical symptoms of Parkinson disease (PD). The mechanisms underlying this early axonal degeneration are, however, still poorly understood. Here, we examined the effects of overexpression of human wildtype alpha-synuclein (alphaSyn-WT), a protein associated with PD, and its mutant variants alphaSyn-A30P and -A53T on neurite morphology and functional parameters in rat primary midbrain neurons (PMN). Moreover, axonal degeneration after overexpression of alphaSyn-WT and -A30P was analyzed by live imaging in the rat optic nerve in vivo. We found that overexpression of alphaSyn WT and of its mutants A30P and A53T impaired neurite outgrowth of PMN and affected neurite branching assessed by Sholl analysis in a variant-dependent manner. Surprisingly, the number of primary neurites per neuron was increased in neurons transfected with alphaSyn. Axonal vesicle transport was examined by live imaging of PMN co-transfected with EGFP-labeled synaptophysin. Overexpression of all alphaSyn variants significantly decreased the number of motile vesicles and decelerated vesicle transport compared with control. Macroautophagic flux in PMN was enhanced by alphaSyn-WT and -A53T but not by alphaSyn-A30P. Correspondingly, colocalization of alphaSyn and the autophagy marker LC3 was reduced for alphaSyn A30P compared with the other alphaSyn variants. The number of mitochondria colocalizing with LC3 as a marker for mitophagy did not differ among the groups. In the rat optic nerve, both alphaSyn-WT and -A30P accelerated kinetics of acute axonal degeneration following crush lesion as analyzed by in vivo live imaging. We conclude that alphaSyn overexpression impairs neurite outgrowth and augments axonal degeneration, whereas axonal vesicle transport and autophagy are severely altered. PMID- 26158518 TI - Estrogen receptor alpha regulates non-canonical autophagy that provides stress resistance to neuroblastoma and breast cancer cells and involves BAG3 function. AB - Breast cancer is a heterogeneous disease and approximately 70% of newly diagnosed breast cancers are estrogen receptor (ER) positive. Out of the two ER types, alpha and beta, ERalpha is the only ER that is detectable by immunohistochemistry in breast cancer biopsies and is the predominant subtype expressed in breast tumor tissue. ER-positive tumors are currently treated with anti-hormone therapy to inhibit ER signaling. It is well known that breast cancer cells can develop endocrine resistance and resistance to anti-hormone therapy and this can be facilitated via the autophagy pathway, but so far the description of a detailed autophagy expression profile of ER-positive cancer cells is missing. In the present study, we characterized tumor cell lines ectopically expressing ERalpha or ERbeta as well as the breast cancer-derived MCF-7 cell line endogenously expressing ERalpha but being ERbeta negative. We could show that ERalpha expressing cells have a higher autophagic activity than cells expressing ERbeta and cells lacking ER expression. Additionally, for autophagy-related gene expression we describe an ERalpha-specific 'autophagy-footprint' that is fundamentally different to tumor cells expressing ERbeta or lacking ER expression. This newly described ERalpha-mediated and estrogen response element (ERE)-independent non-canonical autophagy pathway, which involves the function of the co-chaperone Bcl2-associated athanogene 3 (BAG3), is independent of classical mammalian target of rapamycin (mTOR) and phosphatidylinositol 3 kinase (PI3K) signaling networks and provides stress resistance in our model systems. Altogether, our study uncovers a novel non-canonical autophagy pathway that might be an interesting target for personalized medicine and treatment of ERalpha positive breast cancer cells that do not respond to anti-hormone therapy and classical autophagy inhibitors. PMID- 26158519 TI - Single-cell imaging of inflammatory caspase dimerization reveals differential recruitment to inflammasomes. AB - The human inflammatory caspases, including caspase-1, -4, -5 and -12, are considered as key regulators of innate immunity protecting from sepsis and numerous inflammatory diseases. Caspase-1 is activated by proximity-induced dimerization following recruitment to inflammasomes but the roles of the remaining inflammatory caspases in inflammasome assembly are unclear. Here, we use caspase bimolecular fluorescence complementation to visualize the assembly of inflammasomes and dimerization of inflammatory caspases in single cells. We observed caspase-1 dimerization induced by the coexpression of a range of inflammasome proteins and by lipospolysaccharide (LPS) treatment in primary macrophages. Caspase-4 and -5 were only dimerized by select inflammasome proteins, whereas caspase-12 dimerization was not detected by any investigated treatment. Strikingly, we determined that certain inflammasome proteins could induce heterodimerization of caspase-1 with caspase-4 or -5. Caspase-5 homodimerization and caspase-1/-5 heterodimerization was also detected in LPS primed primary macrophages in response to cholera toxin subunit B. The subcellular localization and organization of the inflammasome complexes varied markedly depending on the upstream trigger and on which caspase or combination of caspases were recruited. Three-dimensional imaging of the ASC (apoptosis associated speck-like protein containing a caspase recruitment domain)/caspase-1 complexes revealed a large spherical complex of ASC with caspase-1 dimerized on the outer surface. In contrast, NALP1 (NACHT leucine-rich repeat protein 1)/caspase-1 complexes formed large filamentous structures. These results argue that caspase-1, -4 or -5 can be recruited to inflammasomes under specific circumstances, often leading to distinctly organized and localized complexes that may impact the functions of these proteases. PMID- 26158520 TI - Loss of apoptosis-inducing factor critically affects MIA40 function. AB - Mitochondrial apoptosis-inducing factor (AIF) influences the oxidative phosphorylation (OXPHOS) system and can be recruited as a mediator of cell death. Pathogenic mutations in the AIFM1 gene cause severe human diseases. Clinical manifestations include inherited peripheral neuropathies, prenatal cerebral abnormalities and progressive mitochondrial encephalomyopathies. In humans, rodents and invertebrates, AIF deficiency results in loss of respiratory complexes and, therefore, impaired OXPHOS. The molecular mechanisms underlying AIF-induced mitochondrial dysfunction remain elusive. Here we show that AIF physically interacts with the oxidoreductase CHCHD4/MIA40. In patient-derived fibroblasts as well as in tissues and glia cells from Harlequin (Hq) mutant mice, AIF deficiency correlates with decreased MIA40 protein levels, without affecting mRNA transcription. Importantly, MIA40 overexpression counteracts loss of respiratory subunits in Hq cells. Together, our findings suggest that MIA40 reduction contributes to the effects of AIF deficiency on OXPHOS, as it may impact on the correct assembly and maintenance of the respiratory subunits. This may be relevant for the development of new therapeutic approaches for AIF-related mitochondrial disorders. PMID- 26158521 TI - FV-162 is a novel, orally bioavailable, irreversible proteasome inhibitor with improved pharmacokinetics displaying preclinical efficacy with continuous daily dosing. AB - Approved proteasome inhibitors have advanced the treatment of multiple myeloma but are associated with serious toxicities, poor pharmacokinetics, and most with the inconvenience of intravenous administration. We therefore sought to identify novel orally bioavailable proteasome inhibitors with a continuous daily dosing schedule and improved therapeutic window using a unique drug discovery platform. We employed a fluorine-based medicinal chemistry technology to synthesize 14 novel analogs of epoxyketone-based proteasome inhibitors and screened them for their stability, ability to inhibit the chymotrypsin-like proteasome, and antimyeloma activity in vitro. The tolerability, pharmacokinetics, pharmacodynamic activity, and antimyeloma efficacy of our lead candidate were examined in NOD/SCID mice. We identified a tripeptide epoxyketone, FV-162, as a metabolically stable, potent proteasome inhibitor cytotoxic to human myeloma cell lines and primary myeloma cells. FV-162 had limited toxicity and was well tolerated on a continuous daily dosing schedule. Compared with the benchmark oral irreversible proteasome inhibitor, ONX-0192, FV-162 had a lower peak plasma concentration and longer half-life, resulting in a larger area under the curve (AUC). Oral FV-162 treatment induced rapid, irreversible inhibition of chymotrypsin-like proteasome activity in murine red blood cells and inhibited tumor growth in a myeloma xenograft model. Our data suggest that oral FV-162 with continuous daily dosing schedule displays a favorable safety, efficacy, and pharmacokinetic profile in vivo, identifying it as a promising lead for clinical evaluation in myeloma therapy. PMID- 26158522 TI - Dicentrine Analogue-Induced G2/M Arrest and Apoptosis through Inhibition of Topoisomerase II Activity in Human Cancer Cells. AB - Lindera megaphylla has been traditionally used as an antineoplastic and wound healing remedy. We previously demonstrated the antitumor effects of D-dicentrine, a natural aporphine alkaloid from the root of L. megaphylla. To generate analogues, series of phenanthrene alkaloids from D-dicentrine were synthesized by degradation with ethyl chloroformate in pyridine, base hydrolysis, and N alkylation. In this study, we demonstrated that one of the synthesized D dicentrine analogues (here after designated as analogue 1) exhibited more potent cytotoxic effects than D-dicentrine in colon adenocarcinoma, hepatoma, leukemia, and epidermoid carcinoma cells. We performed cell cycle and apoptotic analysis by flow cytometry, an apoptotic DNA detection ELISA assay, and topoisomerase II activity by the kinetoplast DNA concatenation assay for studying their cytotoxic mechanisms. We found that both D-dicentrine and analogue 1 induced apoptosis and G2/M arrest in HL-60 leukemia cells. The percentage of apoptotic cells induced by analogue 1 was 4.5-fold higher than that induced by D-dicentrine as evident from measuring the amount of histone-bound DNA fragments. Moreover, we found that analogue 1 was 28-fold more potent than D-dicentrine for inhibition of topoisomerase II activity by the kinetoplast DNA concatenation assay. Our findings indicate that D-dicentrine analogue 1 is very promising as a potential antitumor agent for future study. PMID- 26158524 TI - Balancing the Lifetime and Storage Overhead on Error Correction for Phase Change Memory. AB - As DRAM is facing the scaling difficulty in terms of energy cost and reliability, some nonvolatile storage materials were proposed to be the substitute or supplement of main memory. Phase Change Memory (PCM) is one of the most promising nonvolatile memory that could be put into use in the near future. However, before becoming a qualified main memory technology, PCM should be designed reliably so that it can ensure the computer system's stable running even when errors occur. The typical wear-out errors in PCM have been well studied, but the transient errors, that caused by high-energy particles striking on the complementary metal oxide semiconductor (CMOS) circuit of PCM chips or by resistance drifting in multi-level cell PCM, have attracted little focus. In this paper, we propose an innovative mechanism, Local-ECC-Global-ECPs (LEGE), which addresses both soft errors and hard errors (wear-out errors) in PCM memory systems. Our idea is to deploy a local error correction code (ECC) section to every data line, which can detect and correct one-bit errors immediately, and a global error correction pointers (ECPs) buffer for the whole memory chip, which can be reloaded to correct more hard error bits. The local ECC is used to detect and correct the unknown one-bit errors, and the global ECPs buffer is used to store the corrected value of hard errors. In comparison to ECP-6, our method provides almost identical lifetimes, but reduces approximately 50% storage overhead. Moreover, our structure reduces approximately 3.55% access latency overhead by increasing 1.61% storage overhead compared to PAYG, a hard error only solution. PMID- 26158523 TI - Computing Arm Movements with a Monkey Brainet. AB - Traditionally, brain-machine interfaces (BMIs) extract motor commands from a single brain to control the movements of artificial devices. Here, we introduce a Brainet that utilizes very-large-scale brain activity (VLSBA) from two (B2) or three (B3) nonhuman primates to engage in a common motor behaviour. A B2 generated 2D movements of an avatar arm where each monkey contributed equally to X and Y coordinates; or one monkey fully controlled the X-coordinate and the other controlled the Y-coordinate. A B3 produced arm movements in 3D space, while each monkey generated movements in 2D subspaces (X-Y, Y-Z, or X-Z). With long term training we observed increased coordination of behavior, increased correlations in neuronal activity between different brains, and modifications to neuronal representation of the motor plan. Overall, performance of the Brainet improved owing to collective monkey behaviour. These results suggest that primate brains can be integrated into a Brainet, which self-adapts to achieve a common motor goal. PMID- 26158525 TI - The Effect of NF-kappaB Signalling Pathway on Expression and Regulation of Nacrein in Pearl Oyster, Pinctada fucata. AB - Nacrein is the first identified and widely investigated molluscan matrix protein and is considered to play an important role in the shell formation of the pearl oyster, Pinctada fucata. Here, we investigate the effect of the NF-kappaB signalling pathway on Nacrein gene expression in P. fucata to elucidate the mechanisms involved in shell formation. Inhibition of NF-kappaB signalling decreased Nacrein promoter-dependent luciferase activity. However, co transfection of the Nacrein promoter vector with Pf-IKK or Pf-Rel expression plasmids could enhance luciferase activity, thus proving NF-kappaB signalling could regulate the transcriptional activity of the Nacrein promoter. Gene silencing by RNA interference and subsequent observation of the inner surface of the nacreous layer of oyster shells by SEM, showed that suppression of the gene Pf-Rel lead to a partial inhibition of Nacrein expression, not only at the mRNA level but also at the protein level. The inner surface of the shells became abnormal. Electrophoretic mobility shift assays (EMSAs) revealed that Pf-Rel could directly bind to the relative sites of the Nacrein promoter. These results confirm that an important component of the NF-kappaB signalling pathway, Pf-Rel, can directly bind the Nacrein promoter in P. fucata, and regulate its transcription and shell formation. PMID- 26158526 TI - Selective Reduction of THC's Unwanted Effects through Serotonin Receptor Inhibition. PMID- 26158527 TI - Why do men often not use condoms in their relationships with casual sexual partners in Uganda? AB - With a focus on Uganda, this paper examines men's condom use in sexual relationships with casual partners and what this might tell us about men's vulnerability to HIV-infection. We carried out repeat interviews with 31 men attending a clinic serving women at high risk for HIV infection and their partners in Kampala. We found that the experience of condom-less sex in the men's youth, itself the outcome of a restrictive home environment, was perceived as influencing later unsafe sexual behaviour. Peer pressure encouraged men to have multiple partners. Alcohol negatively affected condom use. Men often opted not to use a condom with women they thought looked healthy, particularly if they had had sex with the same woman before. Some men who were HIV-positive said they saw little point in using condoms since they were already infected. A concerted effort is required to reach men, like those in our study, to halt HIV and the transmission of other sexually transmitted infections. PMID- 26158528 TI - Septic Shock, Community-acquired Pneumonia, New-Onset Atrial Fibrillation, and Intensive Care Unit Outcomes. PMID- 26158529 TI - A Longitudinal Study of Alkaloid Synthesis Reveals Functional Group Interconversions as Bad Actors. PMID- 26158530 TI - DNA vaccines 2014 meeting: Highlights and overview. PMID- 26158532 TI - [Revolution of hepatitis C antiviral therapy: when will Icelanders gain access to the new drugs?[Editorial]]. PMID- 26158531 TI - Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo. AB - Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption. PMID- 26158533 TI - [Why is physical activity on prescription so important in health care? [Editorial]]. PMID- 26158534 TI - [Choledocholithiasis after cholecystectomy at Landspitali--The National University Hospital of Iceland 2008-2011]. AB - INTRODUCTION: Symptoms of choledocholithiasis can appear after cholecystectomy. Stones diagnosed during the first two years following surgery are assumed to have been present at the time of surgery. The purpose of this study was to study patients who presented with choledocholithiasis at Landspitali--The National University Hospital of Iceland, during the period 2008-2011, who had previously undergone cholecystecomy and to assess whether cholodocholithiasis is underdiagnosed at the time of cholecystectomy. MATERIAL AND METHODS: The study was retrospective, data was collected from medical records at Landspitali. Among recorded data were liver function tests, imaging results, time from surgery to diagnosis, treatment and complications. RESULTS: Forty patients presented with choledocholithiasis after previous cholecystectomy. Mean age was 50 years (20-89) and women were 24 (60%). Mean time from surgery to diagnosis was 382 days. Diagnosis was confirmed with imaging in 35 (87.5% cases). Thirty six (90%) patients were treated with ERCP, one with PTC and one underwent open surgery. Three patients healed without treatment. Three patients developed complications from treatment. Thirty one (77.5%) had choledocholithiasis in the first 2 years following surgery. Incidence of previous choledocholithiasis, elevated bilirubin or widening of the choledochus without visible stones where similar for those diagnosed with choledocholithiasis in the first two years and those diagnosed later. CONCLUSION: Majority of patients are treated without surgery. Most stones are diagnosed during the first two years following surgery. For the majority of cases it can not be concluded that stones should have been suspected at time of cholecystectomy. PMID- 26158535 TI - [Delirium after open cardiac surgery:systematic review of prevalence, risk factors and consequences]. AB - Delirium is a sudden and usually transient disturbance in consciousness, attention, cognition, perception and emotions. The pathophysiology is unknown but possible causes include neurotransmitter disturbances and inflammation reaction. Delirium is common in patients after open cardiac surgeries and can lead to serious consequences. Research shows that delirium is an underdiagnosed and undertreated problem. The purpose of this systematic review is to illuminate the prevalence, risk factors and outcome of postoperative delirium following open cardiac surgery. A systematic literature review from 2005-2013 was performed aiming to determine the prevalence, predisposing and precipitating factors and outcome after postoperative delirium following cardiac surgery. Web of Science, PubMed and Cinahl were searched. Findings of the systematic review shows that about one third of patients become delirious after cardiac surgery. Primary predisposing factors are advanced age, cognitive impairment, atrial fibrillation, depression and prior history of stroke. Among precipitating factors are pulmonary bypass, duration of mechanical ventilation, low cardiac output, respiratory failure, pneumonia, infections, blood cell transfusion and post-operative arrhythmias. Delirium causes prolonged hospital stay, reduced activity and higher mortality. Delirium prevention includes reducing risk factors. Delirium is a common and serious complication of open cardiac surgery. Knowledge of risk factors of delirium and regular screening for symptoms of delirium are important to reduce prevalence and to facilitate diagnosis and treatment. PMID- 26158536 TI - [Infection risks associated with importation of fresh food in Iceland]. AB - Access to safe food is a privilege for people living in Iceland. Rapid increase in antimicrobial resistance, related to factory farming and antimicrobial use in agriculture, is a major threat to public health. Increasing food trade between countries and continents facilitates global spread of pathogens and resistance. Icelandic agriculture has benefitted from its isolation and small size. After interventions to reduce the prevalence of Campylobacter and Salmonella at poultry farms, the incidence of human campylobacteriolsis is 17-43/100.000, of which about half is domestically acquired and Salmonella infections 10-15/100.000 mainly acquired abroad. Since Enterohaemorrhagic E. coli (EHEC) has not been detected in domestic cattle, the low incidence of infections is not surprising (0 0.6/100.000/year). A recent outbreak due to a multiresistant EHEC strain was traced to imported lettuce. Antimicrobial use in Icelandic agriculture is among the lowest in Europe and domestic infections caused by Salmonella and Campylobacter are rarely caused by resistant strains. Carbapenemase producing Enterobacteriaceae have not been found in Iceland. Low use of antimicrobials in Icelandic agriculture and actions to limit the spread of Campylobacter and Salmonella have been successful. The public should be informed of the importance of the origin of food and that Icelandic food products are among the safest. PMID- 26158539 TI - Flipping of the coordinated triazine moiety in Cu(I)-L2 and the small electronic factor, kappael, for direct outer-sphere cross reactions: syntheses, crystal structures and redox behaviour of copper(II)/(I)-L2 complexes (L = 3-(2-pyridyl) 5,6-diphenyl-1,2,4-triazine). AB - Six-coordinate [Cu(pdt)2(H2O)2](2+) and four-coordinate [Cu(pdt)2](+) complexes were synthesized and the cross redox reactions were studied in acetonitrile (pdt = 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine). Single crystal analyses revealed that [Cu(pdt)2(H2O)2](BF4)2 was of pseudo-D2h symmetry with two axial water molecules and two symmetrically coordinated equatorial pdt ligands, while the coordination structure of [Cu(pdt)2]BF4 was a squashed tetrahedron (dihedral angle = 54.87 degrees ) with an asymmetric coordination by two pdt ligands: one pdt ligand was coordinated to Cu(i) through pyridine-N and triazine-N2 while another pdt ligand was coordinated through pyridine-N and triazine-N4, and a stacking interaction between the phenyl ring on one pdt ligand and the triazine ring on another pdt ligand caused the squashed structure and non-equivalent Cu-N bond lengths. The cyclic voltammograms for [Cu(pdt)2(H2O)2](2+) and [Cu(pdt)2](+) in acetonitrile were identical to each other and quasi-reversible. The reduction of [Cu(pdt)2(H2O)2](2+) by decamethylferrocene and the oxidation of [Cu(pdt)2](+) by [Co(2,2'-bipyridine)3](3+) in acetonitrile revealed that both cross reactions were sluggish through a gated process (the structural change took place prior to the electron transfer) accompanied by slow direct electron transfer processes. It was found that the triazine ring of the coordinated pdt ligand rotates around the C-C bond between the triazine and pyridine rings with the kinetic parameters k = 51 +/- 5 s(-1) (297.8 K), DeltaH(?) = 6.2 +/- 1.1 kJ mol(-1) and DeltaS(?) = -192 +/- 4 J mol(-1) K(-1). The electron self-exchange process was directly measured using the line-broadening method: kex = (9.9 +/- 0.5) * 10(4) kg mol(-1) s(-1) (297.8 K) with DeltaH(?) = 44 +/- 7 kJ mol(-1) and DeltaS(?) = 0.2 +/- 2.6 J mol( 1) K(-1). By comparing this rate constant with the self-exchange rate constants estimated from the cross reactions using the Marcus cross relation, the non adiabaticity (electronic) factors, kappael, for the direct electron transfer processes between [Cu(pdt)2](+/2+) and non-copper metal (Fe(2+) and Co(3+)) complexes were estimated as ca. 10(-7), indicating that the electronic coupling between the d orbitals of copper and of non-copper metals is very small. PMID- 26158537 TI - TD-60 links RalA GTPase function to the CPC in mitosis. AB - TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical chromosomal passenger complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore-microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by the expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies. PMID- 26158538 TI - Genome-wide burden of deleterious coding variants increased in schizophrenia. AB - Schizophrenia is a common complex disorder with polygenic inheritance. Here we show that by using an approach that compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 controls, schizophrenia cases carry an increased burden of deleterious mutations. At a genome-wide level, our results implicate non-synonymous, splice site as well as stop-altering single-nucleotide variations occurring at minor allele frequency of >= 0.01% in the population. In an independent replication sample of 5,585 schizophrenia cases and 8,103 controls of European ancestry we confirm an enrichment in cases of the alleles identified in our study. In addition, the genes implicated by the increased burden of rare coding variants highlight the involvement of neurodevelopment in the aetiology of schizophrenia. PMID- 26158540 TI - Host Specificity of Ovine Bordetella parapertussis and the Role of Complement. AB - The classical bordetellae are comprised of three subspecies that differ from broad to very limited host specificity. Although several lineages appear to have specialized to particular host species, most retain the ability to colonize and grow in mice, providing a powerful common experimental model to study their differences. One of the subspecies, Bordetella parapertussis, is composed of two distinct clades that have specialized to different hosts: one to humans (Bpphu), and the other to sheep (Bppov). While Bpphu and the other classical bordetellae can efficiently colonize mice, Bppov strains are severely defective in their ability to colonize the murine respiratory tract. Bppov genomic analysis did not reveal the loss of adherence genes, but substantial mutations and deletions of multiple genes involved in the production of O-antigen, which is required to prevent complement deposition on B. bronchiseptica and Bpphu strains. Bppov lacks O-antigen and, like O-antigen mutants of other bordetellae, is highly sensitive to murine complement-mediated killing in vitro. Based on these results, we hypothesized that Bppov failed to colonize mice because of its sensitivity to murine complement. Consistent with this, the Bppov defect in the colonization of wild type mice was not observed in mice lacking the central complement component C3. Furthermore, Bppov strains were highly susceptible to killing by murine complement, but not by sheep complement. These data demonstrate that the failure of Bppov to colonize mice is due to sensitivity to murine, but not sheep, complement, providing a mechanistic example of how specialization that accompanies expansion in one host can limit host range. PMID- 26158541 TI - Metal complexes of curcumin for cellular imaging, targeting, and photoinduced anticancer activity. AB - Curcumin is a polyphenolic species. As an active ingredient of turmeric, it is well-known for its traditional medicinal properties. The therapeutic values include antioxidant, anti-inflammatory, antiseptic, and anticancer activity with the last being primarily due to inhibition of the transcription factor NF-kappaB besides affecting several biological pathways to arrest tumor growth and its progression. Curcumin with all these positive qualities has only remained a potential candidate for cancer treatment over the years without seeing any proper usage because of its hydrolytic instability involving the diketo moiety in a cellular medium and its poor bioavailability. The situation has changed considerably in recent years with the observation that curcumin in monoanionic form could be stabilized on binding to a metal ion. The reports from our group and other groups have shown that curcumin in the metal-bound form retains its therapeutic potential. This has opened up new avenues to develop curcumin-based metal complexes as anticancer agents. Zinc(II) complexes of curcumin are shown to be stable in a cellular medium. They display moderate cytotoxicity against prostate cancer and neuroblastoma cell lines. A similar stabilization and cytotoxic effect is reported for (arene)ruthenium(II) complexes of curcumin against a variety of cell lines. The half-sandwich 1,3,5-triaza-7-phosphatricyclo [3.3.1.1]decane (RAPTA)-type ruthenium(II) complexes of curcumin are shown to be promising cytotoxic agents with low micromolar concentrations for a series of cancer cell lines. In a different approach, cobalt(III) complexes of curcumin are used for its cellular delivery in hypoxic tumor cells using intracellular agents that reduce the metal and release curcumin as a cytotoxin. Utilizing the photophysical and photochemical properties of the curcumin dye, we have designed and synthesized photoactive curcumin metal complexes that are used for cellular imaging by fluorescence microscopy and damaging the cancer cells on photoactivation in visible light while being minimally toxic in darkness. In this Account, we have made an attempt to review the current status of the chemistry of metal curcumin complexes and present results from our recent studies on curcumin complexes showing remarkable in vitro photocytotoxicity. The undesirable dark toxicity of the complexes can be reduced with suitable choice of the metal and the ancillary ligands in a ternary structure. The complexes can be directed to specific subcellular organelles. Selectivity by targeting cancer cells over normal cells can be achieved with suitable ligand design. We expect that this methodology is likely to provide an impetus toward developing curcumin-based photochemotherapeutics for anticancer treatment and cure. PMID- 26158542 TI - Evaluation of a consumer fitness-tracking device to assess sleep in adults. AB - Wearable fitness-tracker devices are becoming increasingly available. We evaluated the agreement between Jawbone UP and polysomnography (PSG) in assessing sleep in a sample of 28 midlife women. As shown previously, for standard actigraphy, Jawbone UP had high sensitivity in detecting sleep (0.97) and low specificity in detecting wake (0.37). However, it showed good overall agreement with PSG with a maximum of two women falling outside Bland-Altman plot agreement limits. Jawbone UP overestimated PSG total sleep time (26.6 +/- 35.3 min) and sleep onset latency (5.2 +/- 9.6 min), and underestimated wake after sleep onset (31.2 +/- 32.3 min) (p's < 0.05), with greater discrepancies in nights with more disrupted sleep. The low-cost and wide-availability of these fitness-tracker devices may make them an attractive alternative to standard actigraphy in monitoring daily sleep-wake rhythms over several days. PMID- 26158543 TI - l0 Gradient Minimization Based Image Reconstruction for Limited-Angle Computed Tomography. AB - In medical and industrial applications of computed tomography (CT) imaging, limited by the scanning environment and the risk of excessive X-ray radiation exposure imposed to the patients, reconstructing high quality CT images from limited projection data has become a hot topic. X-ray imaging in limited scanning angular range is an effective imaging modality to reduce the radiation dose to the patients. As the projection data available in this modality are incomplete, limited-angle CT image reconstruction is actually an ill-posed inverse problem. To solve the problem, image reconstructed by conventional filtered back projection (FBP) algorithm frequently results in conspicuous streak artifacts and gradual changed artifacts nearby edges. Image reconstruction based on total variation minimization (TVM) can significantly reduce streak artifacts in few view CT, but it suffers from the gradual changed artifacts nearby edges in limited-angle CT. To suppress this kind of artifacts, we develop an image reconstruction algorithm based on l0 gradient minimization for limited-angle CT in this paper. The l0-norm of the image gradient is taken as the regularization function in the framework of developed reconstruction model. We transformed the optimization problem into a few optimization sub-problems and then, solved these sub-problems in the manner of alternating iteration. Numerical experiments are performed to validate the efficiency and the feasibility of the developed algorithm. From the statistical analysis results of the performance evaluations peak signal-to-noise ratio (PSNR) and normalized root mean square distance (NRMSD), it shows that there are significant statistical differences between different algorithms from different scanning angular ranges (p<0.0001). From the experimental results, it also indicates that the developed algorithm outperforms classical reconstruction algorithms in suppressing the streak artifacts and the gradual changed artifacts nearby edges simultaneously. PMID- 26158544 TI - Networking in metabolism and human disease. PMID- 26158545 TI - IER3 in pancreatic carcinogenesis. PMID- 26158546 TI - Gatekeepers of pancreas: TEAD and YAP. PMID- 26158547 TI - Radiation holidays stimulate tumor immunity. PMID- 26158548 TI - Alcohol and cardiovascular diseases: where do we stand today? AB - For centuries, multiple medical risks of heavy alcohol drinking have been evident with simultaneous awareness of a less harmful or sensible drinking limit. The increased risks of heavy drinking, defined as three or more standard-sized drinks per day, are both cardiovascular (CV) and non-CV. The CV risks include the following: (i) alcoholic cardiomyopathy (ACM), (ii) systemic hypertension, (iii) atrial arrhythmias, (iv) haemorrhagic stroke and, probably, ischaemic stroke. By contrast, modern epidemiological studies have shown lower morbidity and mortality amongst light-moderate drinkers, due mostly to a reduced risk of coronary artery disease (CAD), with contributions from ischaemic stroke and heart failure (HF). A low level of alcohol drinking has no clear relation to increased risk of any CV condition, except for haemorrhagic stroke. There is good evidence that supports the existence of mechanisms by which alcohol might protect against CAD, but the mechanisms for other alcohol-CV associations remain unclear. Interrelationships amongst the CV conditions affect the individual alcohol-disease relationships; for example, lower CAD risk in light-moderate drinkers is to a large extent responsible for the reduced HF risk. International comparison data plus the presence of proposed beneficial nonalcohol components in wine (particularly in red wine) suggest that this beverage type might afford extra CAD protection. However, the effect of beverage choice is confounded by a healthier drinking pattern and more favourable risk traits in wine drinkers. Debate persists about methodological and public health issues related to the epidemiology of alcohol related CV disease. PMID- 26158549 TI - Histopathology of Explanted Lungs From Patients With a Diagnosis of Pulmonary Sarcoidosis. AB - BACKGROUND: Pathologic features of end-stage pulmonary sarcoidosis (ESPS) are not well defined; anecdotal reports have suggested that ESPS may mimic usual interstitial pneumonia (UIP). We hypothesized that ESPS has distinct histologic features. METHODS: Twelve patients who received a diagnosis of pulmonary sarcoidosis and underwent lung transplantation were included. Control subjects were 10 age- and sex-matched lung transplant patients with UIP. Hematoxylin and eosin-stained tissue sections were examined for the following features: extent/pattern of fibrosis; presence and quantity (per 10 high-power fields) of fibroblast foci and granulomas; distribution and morphology of granulomas; and presence and extent of honeycomb change. Extent of fibrosis and honeycomb change in lung parenchyma was scored as follows: 1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%; 4 = 76% to 100% of lung parenchyma. RESULTS: Eight of 12 cases demonstrated histologic findings typical of ESPS. All showed well-formed granulomas with associated fibrosis distributed in a distinct lymphangitic fashion. Granulomas were present in hilar or mediastinal lymph nodes from six of six patients with ESPS and none of eight control subjects. The extent of fibrosis, honeycomb change, and fibroblast foci was significantly lower in ESPS cases compared with control cases. Two patients with remote histories of sarcoidosis showed histologic features of diseases other than ESPS (UIP and emphysema) without granulomas. Two patients with atypical clinical findings demonstrated nonnecrotizing granulomas combined with either severe chronic venous hypertension or UIP. CONCLUSIONS: ESPS and UIP have distinct histopathologic features in the lungs. Patients with a pretransplant diagnosis of sarcoidosis may develop other lung diseases that account for their end-stage fibrosis. PMID- 26158550 TI - Corrigendum. PMID- 26158552 TI - Robust human body model injury prediction in simulated side impact crashes. AB - This study developed a parametric methodology to robustly predict occupant injuries sustained in real-world crashes using a finite element (FE) human body model (HBM). One hundred and twenty near-side impact motor vehicle crashes were simulated over a range of parameters using a Toyota RAV4 (bullet vehicle), Ford Taurus (struck vehicle) FE models and a validated human body model (HBM) Total HUman Model for Safety (THUMS). Three bullet vehicle crash parameters (speed, location and angle) and two occupant parameters (seat position and age) were varied using a Latin hypercube design of Experiments. Four injury metrics (head injury criterion, half deflection, thoracic trauma index and pelvic force) were used to calculate injury risk. Rib fracture prediction and lung strain metrics were also analysed. As hypothesized, bullet speed had the greatest effect on each injury measure. Injury risk was reduced when bullet location was further from the B-pillar or when the bullet angle was more oblique. Age had strong correlation to rib fractures frequency and lung strain severity. The injuries from a real-world crash were predicted using two different methods by (1) subsampling the injury predictors from the 12 best crush profile matching simulations and (2) using regression models. Both injury prediction methods successfully predicted the case occupant's low risk for pelvic injury, high risk for thoracic injury, rib fractures and high lung strains with tight confidence intervals. This parametric methodology was successfully used to explore crash parameter interactions and to robustly predict real-world injuries. PMID- 26158551 TI - Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA. AB - Pseudogene-derived, long non-coding RNAs (lncRNAs) act as epigenetic regulators of gene expression. Here we present a panel of new mouse Oct4 pseudogenes and demonstrate that the X-linked Oct4 pseudogene Oct4P4 critically impacts mouse embryonic stem cells (mESCs) self-renewal. Sense Oct4P4 transcription produces a spliced, nuclear-restricted lncRNA that is efficiently upregulated during mESC differentiation. Oct4P4 lncRNA forms a complex with the SUV39H1 HMTase to direct the imposition of H3K9me3 and HP1alpha to the promoter of the ancestral Oct4 gene, located on chromosome 17, leading to gene silencing and reduced mESC self renewal. Targeting Oct4P4 expression in primary mouse embryonic fibroblasts causes the re-acquisition of self-renewing features of mESC. We demonstrate that Oct4P4 lncRNA plays an important role in inducing and maintaining silencing of the ancestral Oct4 gene in differentiating mESCs. Our data introduces a sense pseudogene-lncRNA-based mechanism of epigenetic gene regulation that controls the cross-talk between pseudogenes and their ancestral genes. PMID- 26158553 TI - High-sensitivity C-reactive protein predicts 10-year cardiovascular outcome after percutaneous coronary intervention. AB - AIMS: This study aimed to evaluate the prognostic value of high-sensitivity C reactive protein (hsCRP) during 10-year follow-up after percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between April and October 2002, hsCRP was measured in 468 all-comer patients who underwent PCI with sirolimus-eluting stent implantation for stable coronary artery disease or acute coronary syndrome. The primary endpoint was the composite of all-cause mortality or myocardial infarction at 10-year follow-up. Kaplan-Meier event curves displayed ongoing divergence of the hsCRP groups (hsCRP <1 mg/L: 14.7% vs. 1-3 mg/L: 31.1% vs. >3 mg/L: 43.1%). After adjustment for established cardiovascular risk factors and clinical presentation in a Cox regression model, higher CRP levels were associated with a higher incidence of the composite endpoint (>3 mg/L vs. <1 mg/L: HR 2.87, 95% CI: 1.69-4.87, p<0.001; 1-3 mg/L vs. <1 mg/L: HR 2.30, 95% CI: 1.31-4.03, p=0.004). Although adding hsCRP to a prediction model containing conventional cardiovascular risk factors did not significantly improve discriminatory power (area under the receiver operating characteristic curve 0.71 to 0.73, p=0.56), hsCRP was able to improve risk classification (net reclassification index=0.40, p=<0.001). CONCLUSIONS: In patients undergoing PCI, higher CRP levels at the time of the procedure are predictive for 10-year mortality and myocardial infarction. High-sensitivity CRP may be a useful biomarker to improve further risk assessment in patients undergoing PCI. PMID- 26158554 TI - Direct Flow valve-in-valve implantation in a degenerated mitral bioprosthesis. AB - AIMS: Mitral valve reoperations due to failing bioprostheses, in patients affected by multiple comorbidities, are associated with high morbidity and mortality. Transcatheter techniques may evolve as complementary approaches to surgery in these patients at high risk for surgery. METHODS AND RESULTS: We describe a case of Direct Flow 25 mm transcatheter valve implantation as valve-in valve in a degenerated mitral bioprosthesis through a transapical approach in a 63-year-old man affected by dilated cardiomyopathy. The patient was affected by Carpentier-Edwards 29 mm severe regurgitation. The 25 mm Direct Flow bioprosthesis was advanced through the mitral bioprosthesis into the left atrium and then positioned using the three independent positioning wires. Transoesophageal echocardiography evidenced normal Direct Flow function with no paravalvular regurgitation and a low transmitral gradient of 4 mmHg. CONCLUSIONS: Our successful experience, characterised by a Heart Team approach and multidisciplinary patient care, demonstrated the technical feasibility and procedural safety of Direct Flow valve-in-valve mitral implantation. PMID- 26158555 TI - Preprocedural planning and implantation of a transcatheter aortic valve without the use of contrast agent. PMID- 26158557 TI - Selective Fragmentation of Radiation-Sensitive Novel Polymeric Resist Materials by Inner-Shell Irradiation. AB - Two key concepts in extreme ultraviolet lithography (EUVL) are important for it to be a candidate for the mass production of future integrated circuits: the polymer formulation and the photofragmentation process. In this work, both concepts were carefully studied. The design and synthesis of radiation-sensitive organic polymeric materials based on the inclusion of a radiation-sensitive tetrahydrothiophenium functional group are outlined. A 1-(4 methacryloyoxy)naphthalene-1-yl)tetrahydro-1H-thiophenium trifluoromethanesulfonate (MANTMS) monomer containing the tetrahydrothiophenium group undergoes homo- and copolymerizations using free-radical polymerization with a 2,2'-azobis(isobutyronitrile) initiator. The surface photodegradation and oxidation of these novel polymeric materials were investigated using highly monochromatized soft X-rays from synchrotron radiation at the carbon K-edge excitation region. An efficient functionalization was observed when the excitation energy was tuned to C 1s -> pi*C?C. A high rate of defluorination and a loss of sulfonated groups as a result of an increase in the irradiation time for the MANTMS homopolymer thin films were mainly observed under the pi*C?C excitation of the naphthyl functional groups. On the contrary, excitation similar to C 1s -> pi*C?O or C 1s -> sigma*C-F did not produce important degradation, showing a highly selective process of bond breaking. Additionally, the presence of methyl methacrylate copolymer in the original MANTMS yielded a much higher degree of stability against inner-shell radiation damage. Our results highlight the importance of choosing the right polymer formulation and excitation energy to produce a sensitive material for EUVL without using the concept of chemical amplification. PMID- 26158556 TI - A Diffusive Homeostatic Signal Maintains Neural Heterogeneity and Responsiveness in Cortical Networks. AB - Gaseous neurotransmitters such as nitric oxide (NO) provide a unique and often overlooked mechanism for neurons to communicate through diffusion within a network, independent of synaptic connectivity. NO provides homeostatic control of intrinsic excitability. Here we conduct a theoretical investigation of the distinguishing roles of NO-mediated diffusive homeostasis in comparison with canonical non-diffusive homeostasis in cortical networks. We find that both forms of homeostasis provide a robust mechanism for maintaining stable activity following perturbations. However, the resulting networks differ, with diffusive homeostasis maintaining substantial heterogeneity in activity levels of individual neurons, a feature disrupted in networks with non-diffusive homeostasis. This results in networks capable of representing input heterogeneity, and linearly responding over a broader range of inputs than those undergoing non-diffusive homeostasis. We further show that these properties are preserved when homeostatic and Hebbian plasticity are combined. These results suggest a mechanism for dynamically maintaining neural heterogeneity, and expose computational advantages of non-local homeostatic processes. PMID- 26158558 TI - Wilhelm Fliess, Robert Fliess, Ernest Jones, Sandor Ferenczi and Sigmund Freud. PMID- 26158559 TI - Investigating the Potential of Amnion-Based Scaffolds as a Barrier Membrane for Guided Bone Regeneration. AB - Guided bone regeneration is a new concept of large bone defect therapy, which employs a barrier membrane to afford a protected room for osteogenesis and prevent the invasion of fibroblasts. In this study, we developed a novel barrier membrane made from lyophilized multilayered acellular human amnion membranes (AHAM). After decellularization, the AHAM preserved the structural and biomechanical integrity of the amnion extracellular matrix (ECM). The AHAM also showed minimal toxic effects when cocultured with mesenchymal stem cells (MSCs), as evidenced by high cell density, good cell viability, and efficient osteogenic differentiation after 21-day culturing. The effectiveness of the multilayered AHAM in guiding bone regeneration was evaluated using an in vivo rat tibia defect model. After 6 weeks of surgery, the multilayered AHAM showed great efficiency in acting as a shield to avoid the invasion of the fibrous tissues, stabilizing the bone grafts and inducing the massive bone growth. We hence concluded that the advantages of the lyophilized multilayered AHAM barrier membrane are as follows: preservation of the structural and mechanical properties of the amnion ECM, easiness for preparation and handling, flexibility in adjusting the thickness and mechanical properties to suit the application, and efficiency in inducing bone growth and avoiding fibrous tissues invasion. PMID- 26158561 TI - Estimation of the free energy of adsorption of a polypeptide on amorphous SiO2 from molecular dynamics simulations and force spectroscopy experiments. AB - Estimating the free energy of adsorption of materials-binding peptides is fundamental to quantify their interactions across bio/inorganic interfaces, but is difficult to achieve both experimentally and theoretically. We employ a combination of molecular dynamics (MD) simulations and dynamical force spectroscopy experiments based on atomic force microscopy (AFM) to estimate the free energy of adsorption DeltaGads of a (GCRL) tetrapeptide on amorphous SiO2 in pure water. The results of both equilibrium, advanced sampling MD and non equilibrium, steered MD are compared with those of two different approaches used to extract DeltaGads from the dependence of experimentally measured adhesion forces on the applied AFM loading rates. In order to obtain unambiguous peak forces and bond loading rates from steered MD trajectories, we have developed a novel numerical protocol based on a piecewise-harmonic fit of the adhesion work profile along each trajectory. The interpretation of the experiments has required a thorough quantitative characterization of the elastic properties of polyethylene glycol linker molecules used to tether (GCRL)15 polypeptides to AFM cantilevers, and of the polypeptide itself. All obtained DeltaGads values fall within a relatively narrow window between -5 and -9 kcal mol(-1), but can be associated with large relative error bars of more than 50%. Among the different approaches compared, Replica Exchange with Solute Tempering simulations augmented with MetaDynamics (RESTMetaD) and fitting of dynamic force spectroscopy experiments with the model of Friddle and De Yoreo lead to the most reliable DeltaGads estimates. PMID- 26158560 TI - The Effects of Statins on Infections after Stroke or Transient Ischemic Attack: A Meta-Analysis. AB - BACKGROUND: Previous studies have reported that statins can prevent infections, and these findings were ascribed to the anti-inflammatory and immunomodulatory properties of statins. However, the effects of statins on the risk of infection after stroke or transient ischemic attack (TIA) remain controversial. The aim of this study was to evaluate the relationship between statins and the risk of infection after stroke or TIA by means of a meta-analysis. METHODOLOGY AND FINDINGS: Studies were found by searching major electronic databases using key terms and restricting the results to studies published in English language and human studies. Pooled odds ratio (OR) for the association between infection and statins were analyzed using Stata software. A total of five studies that included 8,791 stroke or TIA patients (3,269 patients in the statin use group and 5,522 in the placebo group) were eligible and abstracted. Pooled analysis demonstrated that statins did not significantly affect the incidence of infection after stroke or TIA compared with a placebo (OR 0.819, 95% CI 0.582-1.151, I2 = 64.2%, p= 0.025). Sensitivity analyses showed that the removal of any single study did not significantly affect the pooled OR. Cumulative meta-analysis showed that the incidence of infection did not vary by publication year. No statistical evidence of publication bias was found among the studies selected, based on the results of Egger's (p = 1.000) and Begg's (p = 0.762) tests. CONCLUSIONS: This meta-analysis does not support the hypothesis that statins reduce the risk of infections in stroke or TIA patients. PMID- 26158564 TI - Diaryl Selenide Catalyzed Vicinal Trifluoromethylthioamination of Alkenes. AB - An efficient approach to vicinal trifluoromethylthioamination of alkenes with a broad substrate scope catalyzed by electron-rich diaryl selenide has been developed. This intermolecular amination strategy was successfully applied to SCF3-esterification of alkenes using weak acids as nucleophiles. PMID- 26158562 TI - Association of Diabetic Macular Nonperfusion With Outer Retinal Disruption on Optical Coherence Tomography. AB - IMPORTANCE: Diabetic macular nonperfusion leads to decreased perifoveal capillary blood flow, which in turn causes chronic ischemia of the retinal tissue. Using point-to-point correlation between spectral-domain optical coherence tomography (SD-OCT) and nonperfusion on fluorescein angiography, we observed that retinal capillary nonperfusion is associated with photoreceptor compromise on OCT. This study highlights a new concept of a possible contribution of the retinal deep capillary plexus to photoreceptor compromise in diabetic retinopathy in the absence of diabetic macular edema. OBJECTIVE: To report outer retinal structural changes associated with enlargement of the foveal avascular zone and/or capillary nonperfusion in the macular area of diabetic patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational cross-sectional study in 9 patients who were diagnosed as having diabetic retinopathy without diabetic macular edema and underwent fluorescein angiography and SD-OCT for diabetic retinopathy from July 8, 2014, to December 1, 2014, at a tertiary academic referral center. This analysis was conducted between December 2, 2014, and January 31, 2015. MAIN OUTCOMES AND MEASURES: Outer retinal changes on SD-OCT in areas of macular ischemia. RESULTS: The study included 13 eyes of 9 diabetic patients (4 men and 5 women aged 34-58 years) with a mean duration of diabetes mellitus of 14.5 years. Nine eyes showed outer retinal disruption revealed by SD-OCT that colocalized to areas of enlargement of the foveal avascular zone and macular capillary nonperfusion. Four fellow eyes with normal foveal avascular zones did not show any retinal changes on SD-OCT. CONCLUSIONS AND RELEVANCE: Macular ischemia in diabetic patients can be associated with photoreceptor compromise. The presence of disruption of the photoreceptors on OCT in diabetic patients can be a manifestation of underlying capillary nonperfusion in eyes without diabetic macular edema. Ischemia at the deep capillary plexus may play an important role in these outer retinal changes. PMID- 26158563 TI - Cobalt-Catalyzed Cross-Coupling of Grignards with Allylic and Vinylic Bromides: Use of Sarcosine as a Natural Ligand. AB - Sarcosine was discovered to be an excellent ligand for cobalt-catalyzed carbon carbon cross-coupling of Grignard reagents with allylic and vinylic bromides. The Co(II)/sarcosine catalytic system is shown to perform efficiently when phenyl and benzyl Grignards are coupled with alkenyl bromides. Notably, previously unachievable Co-catalyzed coupling of allylic bromides with Grignards to linearly coupled alpha-products was also realized with Co(II)/sarcosine catalyst. This method was used for efficient preparation of the key intermediate in an alternative synthesis of the antihyperglycemic drug sitagliptin. PMID- 26158565 TI - A Review of Computational Intelligence Methods for Eukaryotic Promoter Prediction. AB - In past decades, prediction of genes in DNA sequences has attracted the attention of many researchers but due to its complex structure it is extremely intricate to correctly locate its position. A large number of regulatory regions are present in DNA that helps in transcription of a gene. Promoter is one such region and to find its location is a challenging problem. Various computational methods for promoter prediction have been developed over the past few years. This paper reviews these promoter prediction methods. Several difficulties and pitfalls encountered by these methods are also detailed, along with future research directions. PMID- 26158566 TI - Synthesis and in Vitro Anti-Tumor Activity of A New Class of Acyclic Thioglycosides. AB - The reaction of sodium 2-cyano-ethylene-1-thiolate salts with 2,3,4,6-tetra-O acetyl-D-gluco- and D-galactopyranosyl bromides and with 2,3,4-tri-O-acetyl-D xylo-. and L-arabinopyranosyl bromides, respectively, afforded new thioglycosides. Heating of the resultout glycosides with hydrazine produced pyrazole derivatives. The cytotoxicities toward the hepatoma cell line (HEPG2) of some synthesized compounds were tested. Some compounds showed high cytotoxic activity against (HEPG2) cell line. The OH moieties in the free glycosides were vital for potency. The synthesis procedures, spectroscopic data and antitumor activities for the prepared compounds are reported herein. PMID- 26158567 TI - Regioselective 1-N-Alkylation and Rearrangement of Adenosine Derivatives. AB - Several methods for the preparation of some N(6)-substituted adenosines based on selective 1-N-alkylation with subsequent Dimroth rearrangement were developed. The proposed methods seem to be effective for the preparation of natural N(6) isopentenyl- and N(6)-benzyladenosines, which are known to possess pronounced biological activities. Direct 1-N-alkylation of 2',3',5'-tri-O-acetyladenosine and 3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides in N,N dimethylformamide (DMF) in the presence of BaCO3 and KI gave 1-N-substituted derivatives with quantitative yields, whereas 1-N-alkylation of adenosine was accompanied by significant O-alkylation. Moreover, the reaction of trimethylsilyl derivatives of N(6)-acetyl-2',3',5'-tri-O-acetyladenosine and N(6)-acetyl-3',5' di-O-acetyl-2'-deoxyadenosine with alkyl halides leads to the formation of the stable 1-N-substituted adenosines. Dimroth rearrangement of 1-N-substituted adenosines in aqueous ammonia yields pure N(6)-substituted adenosines. PMID- 26158568 TI - Synthesis and Biological Evaluations of Click-Generated Nitrogen Mustards. AB - This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological activity of synthesized compounds by testing their cytotoxicity on four representative cancer cell lines A431, JURKAT, K562, and U266. One structure, 1-benzyl-4-(N,N-di-2-chloroethylaminomethyl)-1H [1,2,3]triazole, showed an interesting cytotoxic effect. PMID- 26158569 TI - A New Organic Dye-Based Staining for The Detection of Plant DNA in Agarose Gels. AB - Ethidium bromide (EtBr) is used to stain DNA in agarose gel electrophoresis, but this dye is mutagenic and carcinogenic. We investigated N-719, which is a visible, reliable and organic Ruthenium-based dye, and five fluorescent alternatives for staining plant DNA. For prestaining and poststaining, N-719, GelRed, and SYBR Safe stained both DNA and PCR product bands as clearly as EtBr. SYBR Green I, methylene blue, and crystal violet were effective for poststaining only. The organic dye N-719 stained DNA bands as sensitively and as clearly as EtBr. Consequently, organic dyes can be used as alternatives to EtBr in plant biotechnology studies. PMID- 26158570 TI - Corrigendum. PMID- 26158571 TI - Trachoma Control: 14 Years Later. PMID- 26158572 TI - Global Elimination of Trachoma by 2020: A Work in Progress. PMID- 26158573 TI - Inter-Rater Agreement between Trachoma Graders: Comparison of Grades Given in Field Conditions versus Grades from Photographic Review. AB - PURPOSE: Trachoma surveillance is most commonly performed by direct observation, usually by non-ophthalmologists using the World Health Organization (WHO) simplified grading system. However, conjunctival photographs may offer several benefits over direct clinical observation, including the potential for greater inter-rater agreement. This study assesses whether inter-rater agreement of trachoma grading differs when trained graders review conjunctival photographs compared to when they perform conjunctival examinations in the field. METHODS: Three trained trachoma graders each performed an independent examination of the everted right tarsal conjunctiva of 269 children aged 0-9 years, and then reviewed photographs of these same conjunctivae in a random order. For each eye, the grader documented the presence or absence of follicular trachoma (TF) and intense trachomatous inflammation (TI) according to the WHO simplified grading system. RESULTS: Inter-rater agreement for the grade of TF was significantly higher in the field (kappa coefficient, kappa, 0.73, 95% confidence interval, CI 0.67-0.80) than by photographic review (kappa = 0.55, 95% CI 0.49-0.63; difference in kappa between field grading and photo grading 0.18, 95% CI 0.09 0.26). When field and photographic grades were each assessed as the consensus grade from the three graders, agreement between in-field and photographic graders was high for TF (kappa = 0.75, 95% CI 0.68-0.84). CONCLUSIONS: In an area with hyperendemic trachoma, inter-rater agreement was lower for photographic assessment of trachoma than for in-field assessment. However, the trachoma grade reached by a consensus of photographic graders agreed well with the grade given by a consensus of in-field graders. PMID- 26158574 TI - Risk of Infection with Chlamydia trachomatis from Migrants to Communities Undergoing Mass Drug Administration for Trachoma Control. AB - PURPOSE: To determine the risk of infection with Chlamydia trachomatis in children who are migrants to communities who are undergoing mass drug administration (MDA), and if their neighborhoods have higher rates of infection over time. METHODS: In four communities in Kongwa, Tanzania, all children were enrolled in a longitudinal study of infection and trachoma. New children were identified at census updates as having not been in the community at the previous census. Within communities, neighborhoods were defined as spatially close groups of households, or "balozi". All children in the communities were invited to be examined for trachoma, and have ocular swabs taken for evidence of infection. Trachoma was graded using the World Health Organization simplified grading scheme, and swabs were processed using Amplicor. RESULTS: Children who were migrants were more likely to be infected and to have trachoma than children who were resident in the community, which was significant by the time of the survey following the third year of MDA (odds ratio, OR, 2.49, 95% confidence interval, CI, 1.03-6.05). The neighborhoods where newcomers resided were more likely to have infection a year later than neighborhoods with no migrants, which was most pronounced following the third year of MDA (OR 2.86, 95% CI 1.07-7.65). CONCLUSION: Migrants to communities may be an important source of re-emergent infection, especially as MDA lowers infection among residents. Highly migrant populations may need a special surveillance and treatment program to avoid slowing progress in communities under MDA. PMID- 26158576 TI - Prevalence of Trachoma in Jigawa State, Northwestern Nigeria. AB - PURPOSE: To determine the magnitude of trachoma and the prevalent forms of the disease, and to provide baseline data for the establishment of a trachoma control program in Jigawa State, northwestern Nigeria. METHODS: A population-based cross sectional survey was conducted in Jigawa State in May 2007 using a 2-stage cluster random sampling technique to select 4598 persons from 40 villages based on probability proportional to size. All participants were examined using a penlight and a 2.5 * binocular loupe for signs of trachoma, and graded using the World Health Organization (WHO) simplified grading system. RESULTS: A total of 4598 people were seen with 99.96% coverage. Of these, 2460 (53.5%) were female and 2138 (46.5%) were male. Mean age was 21.6 years ( +/- 19.8 years). The prevalence of follicular trachoma in children aged <=9 years was 20.5% (95% confidence interval, CI, 18.7-22.4%) with no difference between the sexes. The prevalence of trichiasis in adults aged >=15 years was 5%, and the prevalence was higher in females than males (odds ratio 2.60, 95% CI 2.06-3.28; p < 0.001). CONCLUSION: Trachoma is a major problem in Jigawa State; there is a need to train trichiasis surgeons and empower them to carry out community-based surgery. District-level prevalence of trachoma needs to be determined to know which aspects of the WHO SAFE strategy (surgery, antibiotics, facial cleanliness and environmental improvements) need to be emphasized in each district. PMID- 26158575 TI - Baseline Trachoma Mapping in Malawi with the Global Trachoma Mapping Project (GTMP). AB - PURPOSE: To determine the prevalence of trachoma in all suspected endemic districts in Malawi. METHODS: A population-based survey conducted in 16 evaluation units from 12 suspected endemic districts in Malawi (population 6,390,517), using the standardized Global Trachoma Mapping Project (GTMP) protocol. A 2-stage cluster-random sampling design selected 30 households from each of 30 clusters per evaluation unit; all residents aged 1 year and older in selected households were examined for evidence of follicular trachoma (TF), intense trachomatous inflammation (TI), and trachomatous trichiasis (TT). RESULTS: Four of the 16 evaluation units were found to be endemic for trachoma, with a prevalence range of 10.0-13.5% for TF and 0.2-0.6% for TT. Nine evaluation units had a TF prevalence between 5.0% and 9.9% while three evaluation units had a TF prevalence <5.0%. CONCLUSION: The prevalence rates of active trachoma in Malawi were not uniform among suspected endemic evaluation units, with rates higher than the World Health Organization (WHO) threshold for implementation of community-based control measures (TF >= 10.0%) in only 4 of the 16 evaluation units. Trachoma remains a disease of public health importance in some parts of Malawi and adjoining (unmapped) districts should be prioritized for mapping. According to the survey, an additional 3,169,362 people require intervention to reduce active disease and 1557 trichiasis surgeries are needed to reduce the prevalence of TT below WHO recommended thresholds. PMID- 26158578 TI - Lower Postoperative Scar Height is Associated with Increased Postoperative Trichiasis 1 Year after Bilamellar Tarsal Rotation Surgery. AB - PURPOSE: To investigate the relationship between postoperative scar height and surgical success of the bilamellar tarsal rotation (BLTR) procedure, commonly used to correct trichiasis secondary to trachoma. METHODS: Using data from the Partnership for the Rapid Elimination of Trachoma surgical trial, comparing the new trachomatous trichiasis (TT) clamp with standard BLTR instrumentation, 145 sequential participants (245 eyelids) at their 1-year postoperative visit were examined. We measured internal and external scar heights from the upper eyelid margin for nasal, central and temporal sections and compared these to recurrence location at 1 year. We calculated odds of location-specific postoperative trichiasis and examined possible risk factors associated with postoperative trichiasis. RESULTS: A total of 77 eyelids (31%) had postoperative trichiasis, which most commonly occurred centrally. Regardless of instrumentation used, the closer the internal scar was to the eyelid margin, the higher the proportion that had recurrence, until 4.5 mm, at which point, the proportion leveled off. In bivariate analyses, the odds of central recurrence were significantly higher at all three locations when the internal scar height was <4.5 mm compared to higher scars. In multivariate analyses, central scar height <4.5 mm and severe baseline trichiasis were independently associated with central postoperative trichiasis. CONCLUSION: Internal scar height <4.5 mm measured 1 year after surgery is more likely to be associated with postoperative trichiasis. Given these findings and the current World Health Organization recommendation for an incision height of 3.0 mm, further study into optimum incision height to minimize postoperative trichiasis is warranted. PMID- 26158577 TI - Health Beliefs and Perceptions of Trachoma in Communities on the Bijagos Archipelago of Guinea Bissau. AB - PURPOSE: The World Health Organization aims to eliminate blinding trachoma by 2020 using the SAFE strategy: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Trachoma is hyperendemic on the remote Bijagos Archipelago of Guinea-Bissau, West Africa. Sociocultural factors remain unexplored here, despite their potential impact on disease control, particularly through the "F" and "E" aspects. By examining these, we aim to illuminate this population's unreported health beliefs, hygiene behaviors and disease perceptions. This understanding will help to optimize future public health interventions, and guide the distribution of limited healthcare resources. METHODS: Two unmatched interview series were conducted 1 year apart on Bubaque Island in the Bijagos Archipelago; one in rural villages using purposive snowball sampling, the other in a semi-urban settlement, using random-cluster sampling. Interviews were conducted and recorded in Kriolu, the local dialect, by a supervised local field assistant before translation into English for conventional content analysis. RESULTS: Trachoma was unheard of in either series, despite ongoing local trachoma research. A heterogeneous range of disease etiology and preventative measures were suggested, but the importance of hygiene was more widely reported by semi-urban interviewees. Although western medicine was well regarded, traditional practices continued, particularly in the rural populations. CONCLUSIONS: Differences in knowledge, beliefs and behaviors were apparent between the two series. Despite widespread rudimentary knowledge of disease prevention, targeted education might benefit both communities, particularly basic hygiene education for rural communities. Healthcare access should also be improved for rural populations. The impact of these measures could be assessed by future fieldwork. PMID- 26158579 TI - Prevalence and Risk Factors for Trachoma in Rural Areas of Sistan-va-Baluchestan Province, Iran: A Population-Based Study. AB - PURPOSE: To determine the prevalence of trachoma and risk factors associated with the disease in rural areas of the Sistan-va-Baluchestan province in Iran from 2012-2013. Population-based prevalence data for trachoma is lacking in this region. METHODS: In this population-based cross-sectional study, 80 clusters were selected using a systematic and probability proportional to size method. All participants underwent clinical eye examinations according to the World Health Organization simplified trachoma grading system. The prevalence of follicular trachoma (TF) in children aged 1-9 years and the prevalence of trachomatous trichiasis (TT) in women aged over 15 years were the most important clinical indicators of trachoma. RESULTS: The study surveyed 8187 individuals and analyzed 7912 participants (96.6%) including 3737 children aged 1-9 years and 4175 females >15 years. The prevalence of TF and TT in the relevant indicator groups were 0.59% (95% confidence interval, CI, 0.36-0.89%) and 0.02% (95% CI 0.00-0.13%), respectively. CONCLUSION: Previously, trachoma prevalence data for this region were lacking. This study confirms that the Sistan-va-Baluchestan region is not endemic for trachoma. This has important implications for national trachoma elimination activities. PMID- 26158581 TI - Task Shifting for Eye Care in Eastern Africa: General Nurses as Trichiasis Surgeons in Kenya, Malawi, and Tanzania. AB - PURPOSE: There are approximately 8 million people with trachomatous trichiasis globally; in the year 2009, less than 160,000 people had surgery. These numbers are too low in order to achieve the goal of elimination of blinding trachoma by the year 2020. Task shifting approaches have led to the training of general nurses in trichiasis surgery in eastern Africa. The overall aim of this study was to determine the attrition and productivity (and the factors associated with productivity) of trichiasis surgeons in Kenya, Tanzania, and Malawi. METHODS: A 3 year cohort study of trichiasis surgeons. RESULTS: The overall response rate was 86%. Defining high productivity as 50+ operations per year per surgeon, only 16.1% of the trichiasis surgeons were highly productive. Among the surgeons, 27.9% were no longer at their site and ceased providing surgery (attrition) over the 3 years of study. High productivity was associated with having been trained by an experienced trainer, supervised by a clinical officer, having more than three surgical sets, and having an outreach program. CONCLUSION: Attrition of general nurses trained in trichiasis surgery was high. Surgical productivity of trichiasis surgeons remained too low. It is likely that other approaches are needed to address the burden of trichiasis in the three countries. In terms of recommendations, training of trichiasis surgeons should be done in a "package," including a plan for provision of surgical equipment, continuous support and supervision, and outreach. PMID- 26158580 TI - The Global Trachoma Mapping Project: Methodology of a 34-Country Population-Based Study. AB - PURPOSE: To complete the baseline trachoma map worldwide by conducting population based surveys in an estimated 1238 suspected endemic districts of 34 countries. METHODS: A series of national and sub-national projects owned, managed and staffed by ministries of health, conduct house-to-house cluster random sample surveys in evaluation units, which generally correspond to "health district" size: populations of 100,000-250,000 people. In each evaluation unit, we invite all residents aged 1 year and older from h households in each of c clusters to be examined for clinical signs of trachoma, where h is the number of households that can be seen by 1 team in 1 day, and the product h * c is calculated to facilitate recruitment of 1019 children aged 1-9 years. In addition to individual-level demographic and clinical data, household-level water, sanitation and hygiene data are entered into the purpose-built LINKS application on Android smartphones, transmitted to the Cloud, and cleaned, analyzed and ministry-of-health-approved via a secure web-based portal. The main outcome measures are the evaluation unit level prevalence of follicular trachoma in children aged 1-9 years, prevalence of trachomatous trichiasis in adults aged 15 + years, percentage of households using safe methods for disposal of human feces, and percentage of households with proximate access to water for personal hygiene purposes. RESULTS: In the first year of fieldwork, 347 field teams commenced work in 21 projects in 7 countries. CONCLUSION: With an approach that is innovative in design and scale, we aim to complete baseline mapping of trachoma throughout the world in 2015. PMID- 26158582 TI - Population-Based Study of Trachoma in Guatemala. AB - PURPOSE: A prevalence survey for active trachoma in children aged under 10 years and trichiasis in women aged 40 years and older was carried out in four districts in the Solola region in Guatemala, which is suspected of still having a trachoma problem. METHODS: Population-based surveys were undertaken in three districts, within 15 randomly selected communities in each district. In addition, in a fourth district that borders the third district chosen, we surveyed the small northern sub-district, by randomly selecting three communities in each community, 100 children aged under 10 years were randomly selected, and all females over 40 years. Five survey teams were trained and standardized. Trachoma was graded using the World Health Organization simplified grading scheme and ocular swabs were taken in cases of clinical follicular or inflammatory trachoma. Prevalence estimates were calculated at district and sub-district level. RESULTS: Trachoma rates at district level varied from 0-5.1%. There were only two sub-districts where active trachoma approached 10% (Nahuala Costa, 8.1%, and Santa Catarina Costa, 7.3%). Trichiasis rates in females aged 40 years and older varied from 0 3%. Trachoma was likely a problem in the past. CONCLUSIONS: Trachoma is disappearing in the Solola region in Guatemala. Health leadership may consider further mapping of villages around the areas with an especially high rate of trachoma and infection, and instituting trichiasis surgery and active trachoma intervention where needed. PMID- 26158584 TI - Problems and challenges in relation to the treatment of patients with multimorbidity: General practitioners' views and attitudes. AB - OBJECTIVE: To explore views and attitudes among general practitioners (GPs) and researchers in the field of general practice towards problems and challenges related to treatment of patients with multimorbidity. SETTING: A workshop entitled Patients with multimorbidity in general practice held during the Nordic Congress of General Practice in Tampere, Finland, 2013. SUBJECTS: A total of 180 GPs and researchers. DESIGN: Data for this summary report originate from audio recorded, transcribed verbatim plenary discussions as well as 76 short questionnaires answered by attendees during the workshop. The data were analysed using framework analysis. RESULTS: (i) Complex care pathways and clinical guidelines developed for single diseases were identified as very challenging when handling patients with multimorbidity; (ii) insufficient cooperation between the professionals involved in the care of multimorbid patients underlined the GPs' impression of a fragmented health care system; (iii) GPs found it challenging to establish a good dialogue and prioritize problems with patients within the timeframe of a normal consultation; (iv) the future role of the GP was discussed in relation to diminishing health inequality, and current payment systems were criticized for not matching the treatment patterns of patients with multimorbidity. CONCLUSION: The participants supported the development of a future research strategy to improve the treatment of patients with multimorbidity. Four main areas were identified, which need to be investigated further to improve care for this steadily growing patient group. PMID- 26158586 TI - Self-powered smart window controlled by a high open-circuit voltage InGaN/GaN multiple quantum well solar cell. AB - A self-powered complementary electrochromic device (CECD) driven by a high open circuit voltage InGaN/GaN multiple quantum well (MQW) solar cell has been designed. The coloration and bleaching time of the system were 5 and 8 s, respectively. PMID- 26158585 TI - Student-centred GP ambassadors: Perceptions of experienced clinical tutors in general practice undergraduate training. AB - OBJECTIVE: To explore experienced general practitioner (GP) tutor perceptions of a skilled GP tutor of medical students. DESIGN: Interview study based on focus groups. SETTING: Twenty GPs experienced in tutoring medical students at primary health care centres in two Swedish regions were interviewed. METHOD: Four focus group interviews were analysed using qualitative content analysis. SUBJECTS: Twenty GP tutors, median age 50, specifically selected according to age, gender, and location participated in two focus groups in Gothenburg and Malmo, respectively. MAIN OUTCOME MEASURES: Meaning units in the texts were extracted, coded and condensed into categories and themes. RESULTS: Three main themes emerged: "Professional as GP and ambassador to general practice", "Committed and student-centred educator", and "Coordinator of the learning environment". CONCLUSION: Experienced GP tutors describe their skills as a clinical tutor as complex and diversified. A strong professional identity within general practice is vital and GP tutors describe themselves as ambassadors to general practice, essential to the process of recruiting a new generation of general practitioners. Leaders of clinical education and health care planners must understand the complexity in a clinical tutor's assignment and provide adequate support, time, and resources in order to facilitate a sustainable tutorship and a good learning environment, which could also improve the necessary recruitment of future GPs. PMID- 26158587 TI - Learning Multirobot Hose Transportation and Deployment by Distributed Round-Robin Q-Learning. AB - Multi-Agent Reinforcement Learning (MARL) algorithms face two main difficulties: the curse of dimensionality, and environment non-stationarity due to the independent learning processes carried out by the agents concurrently. In this paper we formalize and prove the convergence of a Distributed Round Robin Q learning (D-RR-QL) algorithm for cooperative systems. The computational complexity of this algorithm increases linearly with the number of agents. Moreover, it eliminates environment non sta tionarity by carrying a round-robin scheduling of the action selection and execution. That this learning scheme allows the implementation of Modular State-Action Vetoes (MSAV) in cooperative multi-agent systems, which speeds up learning convergence in over-constrained systems by vetoing state-action pairs which lead to undesired termination states (UTS) in the relevant state-action subspace. Each agent's local state-action value function learning is an independent process, including the MSAV policies. Coordination of locally optimal policies to obtain the global optimal joint policy is achieved by a greedy selection procedure using message passing. We show that D-RR-QL improves over state-of-the-art approaches, such as Distributed Q Learning, Team Q-Learning and Coordinated Reinforcement Learning in a paradigmatic Linked Multi-Component Robotic System (L-MCRS) control problem: the hose transportation task. L-MCRS are over-constrained systems with many UTS induced by the interaction of the passive linking element and the active mobile robots. PMID- 26158589 TI - Healthcare Reform and Preparing the Future Clinical Child and Adolescent Psychology Workforce. AB - The healthcare environment is undergoing important changes for both patients and providers, in part due to the Patient Protection and Affordable Care Act (ACA). Ultimately the healthcare delivery system will function very differently by the end of this decade. These changes will have important implications for the education, training, scientific inquiry, and practice of clinical child and adolescent psychologists. In this article we provide a brief description of the fundamental features of the ACA, with a specific focus on critical components of the act that have important, specific implications for clinical child and adolescents psychologists. We then provide recommendations to help position our field to thrive in the evolving healthcare environment to help facilitate further awareness and promote discussion of both challenges and opportunities that face our field in this evolving health care environment. PMID- 26158590 TI - The first case of Kawasaki disease in a 20-month old baby following immunization with rotavirus vaccine and hepatitis A vaccine in China: A case report. AB - Kawasaki disease (KD) after rotavirus and hepatitis A vaccination has not previously been reported in a baby in China. Herein, we describe a 20-month-old child who developed Kawasaki disease after receiving her second dose of Lanzhou lamb rotavirus vaccine (LLR) and her first dose of freeze-dried live attenuated hepatitis A vaccine. The case report was conducted by collecting and analyzing the hospital in-patient medical records and reviewing both the domestic and foreign pertinent literature. These findings will be important to note this possible side effect and to further investigate the association between the above 2 vaccines and Kawasaki disease. PMID- 26158591 TI - Histopathology of inner ear malformations: Do we have enough evidence to explain pathophysiology? AB - OBJECTIVE: To investigate the histopathology of inner ear malformations (IEMs) in order to explain their pathophysiology. METHOD: Light microscopy was used to study 33 specimens exhibiting various IEMs in the collection of the Otopathology Laboratory at Harvard University's Massachusetts Eye and Ear Infirmary. RESULTS: The investigation found 18 incidences of cochlear hypoplasia (CH) (3 CH-I, 10 CH II, 5 CH-III), 11 incomplete partitions (IPs) (5 IP-I, 6 IP-II), 2 vestibular dilatations, and 2 cases of cochlear nerve aplasia. The IP-I cases had characteristic defective endosteums, while the IP-II cases showed hydropic changes in the scala vestibuli. The CH cases were small in size externally, with normal or defective internal architecture. CONCLUSION: In combination with embryological data, these findings suggest that cases of CH-III and CH-IV are most probably genetically predetermined to be small in size, and that development of the membranous labyrinth stops at a point earlier than normal, so that it is shorter. At the time of complete ossification, this results in a cochlea with small external dimensions and normal internal architecture. In CH-I and CH-II cases, there is arrested development of the internal architecture, in addition to a small cochlea; it is most likely that in these cases, there is a severely defective vascular supply from the internal auditory canal (IAC). IP-I may be the result of a defective vascular supply from the blood vessels of the IAC. In IP II, an enlarged endolymphatic sac (EES) appears to be the genetic abnormality that causes the other abnormalities, as it allows high pressure to be transmitted into the cochlea and vestibule. In IP-III, the pathophysiology appears to be an abnormal vascular supply from the middle ear mucosa, caused by a genetic abnormality and resulting in a thinner otic capsule and the absence of the modiolus. PMID- 26158592 TI - Addition to "The Mechanism of a Ligand-Promoted C(sp(3))-H Activation and Arylation Reaction via Palladium Catalysis: Theoretical Demonstration of a Pd(II)/Pd(IV) Redox Manifold". PMID- 26158593 TI - Snapshots of Proton Accommodation at a Microscopic Water Surface: Understanding the Vibrational Spectral Signatures of the Charge Defect in Cryogenically Cooled H(+)(H2O)(n=2-28) Clusters. AB - We review the role that gas-phase, size-selected protonated water clusters, H(+)(H2O)n, have played in unraveling the microscopic mechanics responsible for the spectroscopic behavior of the excess proton in bulk water. Because the larger (n >= 10) assemblies are formed with three-dimensional cage morphologies that more closely mimic the bulk environment, we report the spectra of cryogenically cooled (10 K) clusters over the size range 2 <= n <= 28, over which the structures evolve from two-dimensional arrangements to cages at around n = 10. The clusters that feature a complete second solvation shell around a surface embedded hydronium ion yield spectral signatures of the proton defect similar to those observed in dilute acids. The origins of the large observed shifts in the proton vibrational signature upon cluster growth were explored with two types of theoretical analyses. First, we calculate the cubic and semidiagonal quartic force constants and use these in vibrational perturbation theory calculations to establish the couplings responsible for the large anharmonic red shifts. We then investigate how the extended electronic wave functions that are responsible for the shapes of the potential surfaces depend on the nature of the H-bonded networks surrounding the charge defect. These considerations indicate that, in addition to the sizable anharmonic couplings, the position of the OH stretch most associated with the excess proton can be traced to large increases in the electric fields exerted on the embedded hydronium ion upon formation of the first and second solvation shells. The correlation between the underlying local structure and the observed spectral features is quantified using a model based on Badger's rule as well as via the examination of the electric fields obtained from electronic structure calculations. PMID- 26158597 TI - Reversible thermo-pneumatic valves on centrifugal microfluidic platforms. AB - Centrifugal microfluidic systems utilize a conventional spindle motor to automate parallel biochemical assays on a single microfluidic disk. The integration of complex, sequential microfluidic procedures on these platforms relies on robust valving techniques that allow for the precise control and manipulation of fluid flow. The ability of valves to consistently return to their former conditions after each actuation plays a significant role in the real-time manipulation of fluidic operations. In this paper, we introduce an active valving technique that operates based on the deflection of a latex film with the potential for real-time flow manipulation in a wide range of operational spinning speeds. The reversible thermo-pneumatic valve (RTPV) seals or reopens an inlet when a trapped air volume is heated or cooled, respectively. The RTPV is a gas-impermeable valve composed of an air chamber enclosed by a latex membrane and a specially designed liquid transition chamber that enables the efficient usage of the applied thermal energy. Inputting thermo-pneumatic (TP) energy into the air chamber deflects the membrane into the liquid transition chamber against an inlet, sealing it and thus preventing fluid flow. From this point, a centrifugal pressure higher than the induced TP pressure in the air chamber reopens the fluid pathway. The behaviour of this newly introduced reversible valving system on a microfluidic disk is studied experimentally and theoretically over a range of rotational frequencies from 700 RPM to 2500 RPM. Furthermore, adding a physical component (e.g., a hemispherical rubber element) to induce initial flow resistance shifts the operational range of rotational frequencies of the RTPV to more than 6000 RPM. An analytical solution for the cooling of a heated RTPV on a spinning disk is also presented, which highlights the need for the future development of time programmable RTPVs. Moreover, the reversibility and gas impermeability of the RTPV in the microfluidic networks are validated on a microfluidic disk designed for performing liquid circulation. Finally, an array of RTPVs is integrated into a microfluidic cartridge to enable sequential aliquoting for the conversion of dengue virus RNA to cDNA and the preparation of PCR reaction mixtures. PMID- 26158598 TI - Catalytic Behavior of Lithium Nitrate in Li-O2 Cells. AB - The development of a successful Li-O2 battery depends to a large extent on the discovery of electrolyte solutions that remain chemically stable through the reduction and oxidation reactions that occur during cell operations. The influence of the electrolyte anions on the behavior of Li-O2 cells was thought to be negligible. However, it has recently been suggested that specific anions can have a dramatic effect on the chemistry of a Li-O2 cell. In the present paper, we describe how LiNO3 in polyether solvents can improve both oxygen reduction (ORR) and oxygen evolution (OER) reactions. In particular, the nitrate anion can enhance the ORR by enabling a mechanism that involves solubilized species like superoxide radicals, which allows for the formation of submicronic Li2O2 particles. Such phenomena were also observed in Li-O2 cells with high donor number solvents, such as dimethyl sulfoxide dimethylformamide (DMF) and dimethylacetamide (DMA). Nevertheless, their instability toward oxygen reduction, lithium metals, and high oxidation potentials renders them less suitable than polyether solvents. In turn, using catalysts like LiI to reduce the OER overpotential might enhance parasitic reactions. We show herein that LiNO3 can serve as an electrolyte and useful redox mediator. NO2(-) ions are formed by the reduction of nitrate ions on the anode. Their oxidation forms NO2, which readily oxidizes to Li2O2. The latter process moves the OER overpotentials down into a potential window suitable for polyether solvent-based cells. Advanced analytical tools, including in situ electrochemical quartz microbalance (EQCM) and ESR plus XPS, HR-SEM, and impedance spectroscopy, were used for the studies reported herein. PMID- 26158599 TI - A comparative study of screening instruments and biomarkers for the detection of cannabis use. AB - BACKGROUND: The aim of this study was to compare the usefulness of 3 different screening instruments (questionnaires) for the detection of cannabis use (CU) with biological markers in blood and hair. METHODS: Ninety-four students were recruited in October 2013. Participants filled out the Severity of Dependence Scale (SDS), the CAGE-AID ("Cut down Annoyed Guilty Eye-opener"-Adapted to Include Drugs), and ProbCannabis-DT questionnaires concerning their possible CU. Blood and hair samples were taken and analyzed by gas chromatography-mass spectrometry. Logistic regression (Nagelkerke R(2)) and receiver operating characteristic (ROC) curve analyses were performed. THCCOOH (Delta(9) tetrahydrocannabinoic acid) plasma of >=5 ng/mL and THC (Delta(9) tetrahydrocannabinol) hair concentrations of >=0.1 and >=0.02 ng/mg were used as the gold standard for CU. The questionnaire results were compared with different concentration ranges for THCCOOH in plasma (<5, 5-75, and >75 ng/mL, indicating the intensity of use) and THC in hair (>=0.02 ng/mg, >=0.1 ng/mg). RESULTS: The Nagelkerke R(2) for comparing the SDS, CAGE-AID, and ProbCannabis-DT with THCCOOH in plasma was 0.350, 0.489, and 0.335, respectively. The area under the ROC curve (95% confidence interval) was 0.772 (0.662-0.882), 0.797 (0.710-0.884), and 0.769 (0.669-0.870), respectively. Corresponding sensitivity/specificity were 70%/84%, 100%/59%, and 87%/67%, respectively. These values were similar to those compared to a 0.02 ng/mg THC cutoff in hair. CONCLUSIONS: Moderate agreement was found between all questionnaires and biomarkers of CU. The CAGE-AID and probCannabis-DT questionnaires were very sensitive, but less specific. SDS was less sensitive, but more specific. PMID- 26158601 TI - Are We There Yet? Biases in Hiring Women Faculty Candidates. PMID- 26158600 TI - Intercomparison of Aerosol Optical Thickness Derived from MODIS and in Situ Ground Datasets over Jaipur, a Semi-arid Zone in India. AB - The first detailed seasonal validation has been carried out for the Moderate Resolution Imaging Spectroradiometer (MODIS) Terra and Aqua satellites Level 2.0 Collection Version 5.1 AOT (tauMODIS) with Aerosol Robotic Network (AERONET) Level 2.0 AOT (tauAERONET) for the years 2009-2012 over semi-arid region Jaipur, northwestern India. The correlation between tauMODIS versus tauAERONET at 550 nm is determined with different spatial and temporal size windows. The tauMODIS overestimates tauAERONET within a range of +0.06 +/- 0.24 during the pre-monsoon (April-June) season, while it underestimates the tauAERONET with -0.04 +/- 0.12 and -0.05 +/- 0.18 during dry (December-March) and post-monsoon (October November) seasons, respectively. Correlation without (with) error envelope has been found for pre-monsoon at 0.71 (0.89), post-monsoon at 0.76 (0.94), and dry season at 0.78 (0.95). tauMODIS is compared to tauAERONET at three more ground AERONET stations in India, i.e., Kanpur, Gual Pahari, and Pune. Furthermore, the performance of MODIS Deep Blue and Aqua AOT550 nm (tauDB550 nm and tauAqua550 nm) with tauAERONET is also evaluated for all considered sites over India along with a U.S. desert site at White Sand, Tularosa Basin, NM. The statistical results reveal that tauAqua550 nm performs better over Kanpur and Pune, whereas tauDB550 nm performs better over Jaipur, Gual Pahari, and White Sand High Energy Laser Systems Test Facility (HELSTF) (U.S. site). PMID- 26158604 TI - An Unhealthy Start in Life- What Matters Most? PMID- 26158602 TI - Vibronic origin of long-lived coherence in an artificial molecular light harvester. AB - Natural and artificial light-harvesting processes have recently gained new interest. Signatures of long-lasting coherence in spectroscopic signals of biological systems have been repeatedly observed, albeit their origin is a matter of ongoing debate, as it is unclear how the loss of coherence due to interaction with the noisy environments in such systems is averted. Here we report experimental and theoretical verification of coherent exciton-vibrational (vibronic) coupling as the origin of long-lasting coherence in an artificial light harvester, a molecular J-aggregate. In this macroscopically aligned tubular system, polarization-controlled 2D spectroscopy delivers an uncongested and specific optical response as an ideal foundation for an in-depth theoretical description. We derive analytical expressions that show under which general conditions vibronic coupling leads to prolonged excited-state coherence. PMID- 26158603 TI - Neurotoxicants, Micronutrients, and Social Environments: Individual and Combined Effects on Children's Development. AB - -Systematic research evaluating the separate and interacting impacts of neurotoxicants, micronutrients, and social environments on children's cognition and behavior has only recently been initiated. Years of extensive human epidemiologic and animal experimental research document the deleterious impact of lead and other metals on the nervous system. However, discrepancies among human studies and between animal and human studies underscore the importance of variations in child nutrition as well as social and behavioral aspects of children's environments that mitigate or exacerbate the effects of neurotoxicants. In this monograph, we review existing research on the impact of neurotoxic metals, nutrients, and social environments and interactions across the three domains. We examine the literature on lead, mercury, manganese, and cadmium in terms of dispersal, epidemiology, experimental animal studies, effects of social environments, and effects of nutrition. Research documenting the negative impact of lead on cognition and behavior influenced reductions by the Center for Disease Control in child lead-screening guidelines from 30 micrograms per deciliter (MUg/dL) in 1975 to 25 MUg/dL in 1985 and to 10 MUg/dL in 1991. A further reduction is currently being considered. Experimental animal research documents lead's alteration of glutamate-neurotransmitter (particularly N-methyl D-aspartate) activity vital to learning and memory. In addition, lead induces changes in cholinergic and dopaminergic activity. Elevated lead concentrations in the blood are more common among children living in poverty and there is some evidence that socioeconomic status influences associations between lead and child outcomes. Micronutrients that influence the effects of lead include iron and zinc. Research documenting the negative impact of mercury on children (as well as adults) has resulted in a reference dose (RfD) of 0.1 microgram per kilogram of body weight per day (MUg/kg/day). In animal studies, mercury interferes with glutamatergic, cholinergic, and dopaminergic activity. Although evidence for interactions of mercury with children's social contexts is minimal, researchers are examining interactions of mercury with several nutrients. Research on the effects of cadmium and manganese on child cognition and behavior is just beginning. Experimental animal research links cadmium to learning deficits, manganese to behaviors characteristic of Parkinson's disease, and both to altered dopaminergic functioning. We close our review with a discussion of policy implications, and we recommend interdisciplinary research that will enable us to bridge gaps within and across domains. PMID- 26158605 TI - Testosterone Replacement in Androgen-Deficient Men With Ejaculatory Dysfunction: A Randomized Controlled Trial. AB - CONTEXT: Low T levels have been associated with ejaculatory dysfunction (EjD) in cross-sectional studies; however, the efficacy of T replacement in improving EjD has not been studied in a randomized controlled trial. OBJECTIVE: To evaluate the efficacy of T replacement in androgen-deficient men with EjD. DESIGN: A multicenter, double-blind, randomized, placebo-controlled, 16-week trial with T solution 2% versus placebo. SETTING: Medical centers in the United States, Canada, and Mexico. PATIENTS OR OTHER PARTICIPANTS: Seventy-six men with one or more EjD symptoms, including delayed ejaculation, anejaculation, reduced ejaculate volume, and/or reduced force of ejaculation, and two total T levels <300 ng/dL (<10.41 nmol/L) measured with liquid chromatography tandem mass spectrometry. INTERVENTIONS: Sixty milligrams of T solution 2% or placebo applied to the axillae for 16 weeks. MAIN OUTCOME MEASURES: The primary outcome was a change in the score of the three-item Male Sexual Health Questionnaire Ejaculatory Dysfunction-Short Form (MSHQ-EjD-SF); secondary outcomes included measured ejaculate volume, scores of the bother/satisfaction item of the MSHQ-EjD SF, the orgasmic function domain of the International Index of Erectile Function Questionnaire, and the sexual activity log. RESULTS: Seventy-six participants were randomized; 66 completed the study. Baseline demographic and clinical characteristics were comparable between the treatment arms. T replacement improved the MSHQ-EjD-SF score (mean score change, +3.1); however, this effect was not statistically different from placebo (mean score change, +2.5; P = .596). No differences were seen in any of the secondary outcomes or frequency of adverse events. CONCLUSION: T replacement was not associated with significant improvement in EjD in androgen-deficient men. PMID- 26158606 TI - Large-Scale Discovery and Validation Studies Demonstrate Significant Reductions in Circulating Levels of IL8, IL-1Ra, MCP-1, and MIP-1beta in Patients With Type 1 Diabetes. AB - CONTEXT: Previous studies have attempted to elucidate the potential role of various cytokines and chemokines in human type 1 diabetes (T1D); however, the precise role of these serum proteins in T1D is still controversial and undetermined primarily due to the small sample sizes of the previous studies. We profiled a panel of serum cytokines and chemokines using a large-scale, two-stage study design for the discovery and validation of the serum proteins associated with T1D. PARTICIPANTS: The participants were patients with T1D and islet autoantibody-negative control subjects from the Phenome and Genome of Diabetes Autoimmunity study. MAIN OUTCOME MEASURES: Thirteen cytokines and chemokines were measured in serum of 4424 subjects using multiplex immunoassays. RESULTS: Using 1378 samples in Stage 1, we found that four of the 13 proteins are significantly lower in patients with T1D than controls (IL8: odds ratio [OR] = 0.40; P = 5.7 * 10(-19); IL-1Ra: OR = 0.42; P = 1.1 * 10(-13); MCP-1: OR = 0.60; P = 6.7 * 10( 9); and MIP-1beta: OR = 0.63; P = 4.2 * 10(-7)). Our confirmation data with 3046 samples in Stage 2 further confirmed the significant negative associations of these four proteins with T1D (IL8: OR = 0.43; P = 8.9 * 10(-32); IL-1Ra: OR = 0.56, P = 3.7 * 10(-27); MCP-1: OR = 0.61, P = 4.3 * 10(-17); and MIP-1beta: OR = 0.69, P = 2.4 * 10(-13)). Quartile analyses also suggested that significantly more T1D cases have protein levels in the bottom quartile than in the top quartile for all four proteins: IL8 (OR = 0.09), IL-1Ra (OR = 0.18), MCP-1 (OR = 0.38), and MIP-1beta (OR = 0.44). Furthermore, the negative associations between T1D and serum levels of all four proteins are stronger in genetically high-risk groups compared with the moderate and low-risk groups. CONCLUSIONS: IL8, IL-1Ra, MCP-1, and MIP-1beta are significantly lower in patients with T1D than controls. PMID- 26158608 TI - Progress of Diabetic Severity and Risk of Dementia. AB - CONTEXT: Diabetes is a risk factor for dementia, but the effects of diabetic severity on dementia are unclear. OBJECTIVE: The purpose of this study was to investigate the association between the severity and progress of diabetes and the risk of dementia. DESIGN AND SETTING: We conducted a 12-year population-based cohort study of new-onset diabetic patients from the Taiwan National Health Insurance Research Database. The diabetic severity was evaluated by the adapted Diabetes Complications Severity Index (aDCSI) from the prediabetic period to the end of follow-up. Cox proportional hazard regressions were used to calculate the hazard ratios (HRs) of the scores and change in the aDCSI. PARTICIPANTS: Participants were 431,178 new-onset diabetic patients who were older than 50 years and had to receive antidiabetic medications. MAIN OUTCOME: Dementia cases were identified by International Classification of Diseases, ninth revision, code (International Classification of Diseases, ninth revision, codes 290.0, 290.1, 290.2, 290.3, 290.4, 294.1, 331.0), and the date of the initial dementia diagnosis was used as the index date. RESULTS: The scores and change in the aDCSI were associated with the risk of dementia when adjusting for patient factors, comorbidity, antidiabetic drugs, and drug adherence. At the end of the follow-up, the risks for dementia were 1.04, 1.40, 1.54, and 1.70 (P < .001 for trend) in patients with an aDCSI score of 1, 2, 3, and greater than 3, respectively. Compared with the mildly progressive patients, the adjusted HRs increased as the aDCSI increased (2 y HRs: 1.30, 1.53, and 1.97; final HRs: 2.38, 6.95, and 24.0 with the change in the aDCSI score per year: 0.51-1.00, 1.01-2.00, and > 2.00 vs < 0.50 with P < .001 for trend). CONCLUSIONS: The diabetic severity and progression reflected the risk of dementia, and the early change in the aDCSI could predict the risk of dementia in new-onset diabetic patients. PMID- 26158609 TI - Copeptin, Insulin Resistance, and Risk of Incident Diabetes in Older Men. AB - CONTEXT: Prior studies suggested a role for the arginine vasopressin (AVP) system in the pathogenesis of diabetes. Prospective studies on the association between copeptin (the C-terminal fragment of AVP hormone) and incident diabetes are limited. OBJECTIVE: We have examined the association between plasma copeptin and the risk of incident diabetes in older men. DESIGN: The British Regional Heart Study was a prospective study with an average of 13 years follow-up. SETTING: General practices in the United Kingdom were studied. PARTICIPANTS: Participants were 3226 men aged 60 to 79 years with no prevalent diabetes. OUTCOME: We measured 253 patients with incident diabetes. RESULTS: Copeptin was positively and significantly associated with renal dysfunction, insulin resistance (homeostasis model assessment of insulin resistance), metabolic risk factors (waist circumference, blood pressure, triglycerides, and liver function), C reactive protein, tissue plasminogen activator, and von Willebrand factor (endothelial dysfunction) but not with plasma glucose. The risk of incident diabetes was significantly elevated only in men in the top fifth of the copeptin distribution (>6.79 pmol/L), and this risk persisted after adjustment for several diabetes risk factors including metabolic risk factors and C-reactive protein (adjusted hazard ratio in the top fifth vs the rest = 1.78 [95% confidence interval, 1.34-2.37]). Risk was markedly attenuated although it remained significant after further adjustment for homeostasis model assessment of insulin resistance and plasma glucose (adjusted hazard ratio = 1.47 [1.11-1.97]). The increased risk was seen even when the analysis was restricted to men with no chronic kidney disease or to men with no impaired fasting glucose (<6.1 mmol/L). CONCLUSION: Copeptin is associated with a significantly increased risk of diabetes in older men. The association is partly mediated through lower insulin sensitivity. The findings suggest a potential role of the AVP system in diabetes. PMID- 26158610 TI - Assessment of Tandem Measurements of pH and Total Gut Transit Time in Healthy Volunteers. AB - OBJECTIVES: The variation of luminal pH and transit time in an individual is unknown, yet is necessary to interpret single measurements. This study aimed to assess the intrasubject variability of gut pH and transit time in healthy volunteers using SmartPill devices (Covidien, Minneapolis, MN). METHODS: Each subject (n=10) ingested two SmartPill devices separated by 24 h. Mean pH values were calculated for 30 min after gastric emptying (AGE), before the ileocecal (BIC) valve, after the ileocecal (AIC) valve, and before body exit (BBE). Intrasubject variability was determined by comparing mean values from both ingestions for an individual subject using standard deviations, 95% limits of agreement, and Bland-Altman plots. RESULTS: Tandem device ingestion occurred without complication. The median (full range) intrasubject standard deviations for pH were 0.02 (0.0002-0.2048) for AGE, 0.06 (0.0002-0.3445) for BIC, 0.14 (0.0018-0.3042) for AIC, and 0.08 (0.0098-0.5202) for BBE. There was a significant change in pH for AIC (mean difference: -0.45+/-0.31, P=0.0015) observed across all subjects. The mean coefficients of variation for transit time were 12.0+/-7.4% and 25.8+/-15.8% for small and large bowels, respectively (P=0.01). CONCLUSIONS: This study demonstrates the safety and feasibility of tandem gut transit and pH assessments using the SmartPill device. In healthy individuals and over 24 h, the gut pH profile does not markedly fluctuate in a given region with more variation seen in the colon compared with the small bowel, which has important implications for future physiology and drug delivery studies. PMID- 26158607 TI - Conventional and Nuclear Medicine Imaging in Ectopic Cushing's Syndrome: A Systematic Review. AB - CONTEXT: Ectopic Cushing's Syndrome (ECS) can be a diagnostic challenge with the hormonal source difficult to find. This study analyzes the accuracy of imaging studies in ECS localization. EVIDENCE ACQUISITION: Systematic review of medical literature for ECS case series providing individual patient data on at least one conventional imaging technique (computed tomography [CT]/magnetic resonance imaging) and one of the following: 111In-pentetreotide (OCT), 131I/123I metaiodobenzylguanidine, 18Ffluoro-2-deoxyglucose-positron emission tomography (FDG-PET), 18F-fluorodopa-PET (F-DOPA-PET), 68Ga- DOTATATE-PET/CT or 68Ga-DOTATOC PET/CT scan (68Gallium-SSTR-PET/CT). EVIDENCE SUMMARY: The analysis comprised 231 patients (females, 50.2%; age, 42.617 y). Overall, 52.4%(121/231) had "overt" ECS,18.6% had "occult" ECS, and 29% had "covert" ECS. Tumors were located in the lung (55.3%), mediastinum-thymus (7.9%), pancreas (8.5%), adrenal glands (6.4%), gastrointestinal tract (5.4%), thyroid (3.7%), and other sites (12.8%), and primary tumors were mostly bronchial neuroendocrine tumors (NETs) (54.8%), pancreatic NETs (8%), mediastinum-thymus NETs (6.9%), gastrointestinal NETs (5.3%), pheochromocytoma (6.4%), neuroblastoma (3.2%), and medullary thyroid carcinoma (3.2%). Tumors were localized byCTin66.2%(137/207), magnetic resonance imaging in 51.5% (53/103), OCT in 48.9% (84/172), FDG-PET in 51.7% (46/89), F DOPAPET in 57.1% (12/21), 131/123I-metaiodobenzylguanidine in 30.8% (4/13), and 68Gallium-SSTRPET/CT in 81.8% (18/22) of cases. Molecular imaging discovered 79.1% (53/67) of tumors unidentified by conventional radiology, with OCT the most commonly used, revealing the tumor in 64%, followed by FDG-PET in 59.4%. F-DOPA PET was used in only seven covert cases (sensitivity, 85.7%). Notably, 68Gallium SSTR-PET/CT had 100% sensitivity among covert cases. CONCLUSIONS: Nuclear medicine improves the sensitivity of conventional radiology when tumor site identification is problematic. OCT offers a good availability/reliability ratio, and FDG-PET was proven useful. 68Gallium-SSTR-PET/CT use was infrequent, despite offering the highest sensitivity. PMID- 26158611 TI - C. difficile Infection: Changing Epidemiology and Management Paradigms. AB - The incidence of Clostridium difficile infection (CDI) has been rising in hospitals, long-term care facilities, and within the community. Cases have been more severe with more complications, deaths, and higher healthcare-associated costs. With the emergence of a hypervirulent strain of C. difficile and the increasing prevalence of community-acquired CDI among healthy patients without traditional risk factors, the epidemiology of C. difficile has been evolving. This changing epidemiology requires a change in management. Taking into account new risk factors for CDI and growing subpopulations of affected individuals, diagnostic, treatment, and prevention approaches need to be adjusted. PMID- 26158612 TI - Minimally Invasive Versus Open Pancreaticoduodenectomy for Cancer: Practice Patterns and Short-term Outcomes Among 7061 Patients. AB - OBJECTIVES: To describe national practice patterns regarding utilization of minimally invasive pancreaticoduodenectomy (MIPD) and compare short-term outcomes with those following open pancreaticoduodenectomy for cancer. BACKGROUND: There is increasing interest in use of MIPD; however, published data are limited to single institutional experiences. METHODS: Adult patients undergoing pancreaticoduodenectomy were identified from the National Cancer Database, 2010 2011. Descriptive statistics and multivariable modeling were employed to characterize use of MIPD (laparoscopic or robotic) and compare short-term outcomes to those following open pancreaticoduodenectomy. RESULTS: A total of 7061 patients underwent pancreaticoduodenectomy: 983 had MIPD and 6078 had open procedures. The use of MIPD increased by 45% (179 cases) from 2010 to 2011. The majority of hospitals (92%) performing MIPD were low volume (<= 10 cases/2 years). Factors independently associated with undergoing MIPD included fewer comorbidities, treatment at an academic institution, and a neuroendocrine tumor diagnosis (all P < 0.01). The unadjusted 30-day mortality rate was 5.1% for MIPD versus 3.1% after open surgery. For patients with adenocarcinoma, there were no differences between MIPD and open pancreaticoduodenectomy after multivariable adjustment in number of lymph nodes removed, rate of positive surgical margins, length of stay, or readmissions. However, 30-day mortality was higher for patients undergoing MIPD versus open surgery (odds ratio = 1.87, confidence interval: 1.25-2.80, P = 0.002). CONCLUSIONS: While there is increasing interest in employing MIPD for adenocarcinoma, its use is associated with increased 30-day mortality. The majority of hospitals performing MIPD were low volume. These results may suggest that MIPD is a complex procedure for which comprehensive protocols outlining criteria for implementation might be warranted to optimize patient safety. PMID- 26158613 TI - [The Beautiful Gardens of Psychosomatic Medicine and Psychotherapy]. PMID- 26158614 TI - [Relational Frame Theory--A Theoretical Framework for Contextual Behavioral Science]. AB - Therapists have to deal with verbal systems and often work with verbal exchange. Therefore, a psychological theory is required, which teaches the therapist how to accomplish this task. The BRT is a theory of human language and cognition that explains how people use their verbal behavior as stimuli in their interrelations and how they act and react, based on the resulting relationships. This behavior is learned very early in the course of language acquisition and functions as a generalized operant. A prerequisite for this is the ability of people to undergo mental simulation. This enables them to construct diverse relational frameworks between individual stimuli. Without relational frameworks, people cannot function. The ability to establish a relational framework is a prerequisite for the formation of rule-governed behavior. Rule-governed behavior economizes complex decision processes, creates interpersonal security and enables dealing with events before they take place. On the other hand, the same properties that enable people to solve problems effectively can also contribute to rigid adherence to rules and experience avoidance. Relational frameworks, once established, outweigh other sources of behavioral regulation. Thus, it can become the basis of psychopathology. Poor contextual control makes it difficult for people to devote flexible, focused and voluntary attention to the present and align their actions with the immediate present. Contextual psychotherapy methods that are based on the BRT start precisely at this point: Targeted establishment of new contingencies in the therapeutic interaction through systematic strengthening of metacognitive mode and through the establishment of new rules that make possible a change in the rule-governed behavior enable undermining of dysfunctional rule-governed behavior and build up desirable behavior. This allows any therapeutic process to be more effective--regardless of the patient's expressed symptoms. PMID- 26158615 TI - Building an organic computing device with multiple interconnected brains. AB - Recently, we proposed that Brainets, i.e. networks formed by multiple animal brains, cooperating and exchanging information in real time through direct brain to-brain interfaces, could provide the core of a new type of computing device: an organic computer. Here, we describe the first experimental demonstration of such a Brainet, built by interconnecting four adult rat brains. Brainets worked by concurrently recording the extracellular electrical activity generated by populations of cortical neurons distributed across multiple rats chronically implanted with multi-electrode arrays. Cortical neuronal activity was recorded and analyzed in real time, and then delivered to the somatosensory cortices of other animals that participated in the Brainet using intracortical microstimulation (ICMS). Using this approach, different Brainet architectures solved a number of useful computational problems, such as discrete classification, image processing, storage and retrieval of tactile information, and even weather forecasting. Brainets consistently performed at the same or higher levels than single rats in these tasks. Based on these findings, we propose that Brainets could be used to investigate animal social behaviors as well as a test bed for exploring the properties and potential applications of organic computers. PMID- 26158617 TI - Epigenetic mechanisms and therapeutic targets of chemotherapy resistance in epithelial ovarian cancer. AB - Epithelial ovarian cancer is the most lethal gynaecological cancer with the majority of patients succumbing to chemotherapy-resistant disease. Unravelling the mechanisms of drug resistance and how it can be prevented or reversed is a pivotal challenge in the treatment of cancer. Epigenetic mechanisms appear to play a crucial role in the development of inherent and acquired resistance in ovarian cancer. Aberrant epigenetic states can be reversed by drug therapy, and thus maintenance of epigenetic change is a potential target to halt or reverse chemotherapy resistance. This review explores the evidence that demonstrates that DNA methylation, histone modification, and microRNAs are associated with inherent and acquired chemotherapy resistance in ovarian cancer and the current challenges associated with this. We also explore current epigenetic therapies used in patients with drug-resistant ovarian cancer and future potential targets. PMID- 26158618 TI - Free-Base and Protonated Nicotine in Electronic Cigarette Liquids and Aerosols. AB - As with other tobacco aerosols, nicotine delivery from e-cigarettes (ECIG) depends on the total nicotine and its partitioning between free-base (Nic) and protonated (NicH(+)) forms. Previous studies of ECIG nicotine emissions have generally reported "nicotine yield" without attention to whether the methods employed resulted in quantification of the total nicotine or only one of its forms, making reported results difficult to compare across studies or to evaluate against reported blood exposure. This study reports a convenient solvent extraction method for determining total nicotine and its partitioning in ECIG liquids and aerosols by gas chromatography. Commercial ECIG liquids and aerosols were analyzed, and it was found that most of the nicotine was in the Nic form, with aerosols exhibiting higher Nic fraction than the parent liquids. Apparent pH was found to correlate with nicotine partitioning and can provide a useful indirect measure when chromatography is unavailable. Finally, labeled ECIG liquid nicotine concentration in commercial products was often inconsistent with measured nicotine. PMID- 26158616 TI - Introgression of the SbASR-1 gene cloned from a halophyte Salicornia brachiate enhances salinity and drought endurance in transgenic groundnut (arachis hypogaea)and acts as a transcription factor [corrected]. AB - The SbASR-1 gene, cloned from a halophyte Salicornia brachiata, encodes a plant specific hydrophilic and stress responsive protein. The genome of S. brachiata has two paralogs of the SbASR-1 gene (2549 bp), which is comprised of a single intron of 1611 bp, the largest intron of the abscisic acid stress ripening [ASR] gene family yet reported. In silico analysis of the 843-bp putative promoter revealed the presence of ABA, biotic stress, dehydration, phytohormone, salinity, and sugar responsive cis-regulatory motifs. The SbASR-1 protein belongs to Group 7 LEA protein family with different amino acid composition compared to their glycophytic homologs. Bipartite Nuclear Localization Signal (NLS) was found on the C-terminal end of protein and localization study confirmed that SbASR-1 is a nuclear protein. Furthermore, transgenic groundnut (Arachis hypogaea) plants over expressing the SbASR-1 gene constitutively showed enhanced salinity and drought stress tolerance in the T1 generation. Leaves of transgenic lines exhibited higher chlorophyll and relative water contents and lower electrolyte leakage, malondialdehyde content, proline, sugars, and starch accumulation under stress treatments than wild-type (Wt) plants. Also, lower accumulation of H2O2 and O2.- radicals was detected in transgenic lines compared to Wt plants under stress conditions. Transcript expression of APX (ascorbate peroxidase) and CAT (catalase) genes were higher in Wt plants, whereas the SOD (superoxide dismutase) transcripts were higher in transgenic lines under stress. Electrophoretic mobility shift assay (EMSA) confirmed that the SbASR-1 protein binds at the consensus sequence (C/G/A)(G/T)CC(C/G)(C/G/A)(A/T). Based on results of the present study, it may be concluded that SbASR-1 enhances the salinity and drought stress tolerance in transgenic groundnut by functioning as a LEA (late embryogenesis abundant) protein and a transcription factor. PMID- 26158619 TI - Neglect and Motion Stimuli--Insights from a Touchscreen-Based Cancellation Task. AB - BACKGROUND AND PURPOSE: In stroke patients, neglect diagnostic is often performed by means of paper-pencil cancellation tasks. These tasks entail static stimuli, and provide no information concerning possible changes in the severity of neglect symptoms when patients are confronted with motion. We therefore aimed to directly contrast the cancellation behaviour of neglect patients under static and dynamic conditions. Since visual field deficits often occur in neglect patients, we analysed whether the integrity of the optic radiation would influence cancellation behaviour. METHODS: Twenty-five patients with left spatial neglect after right-hemispheric stroke were tested with a touchscreen cancellation task, once when the evenly distributed targets were stationary, and once when the identic targets moved with constant speed on a random path. The integrity of the right optic radiation was analysed by means of a hodologic probabilistic approach. RESULTS: Motion influenced the cancellation behaviour of neglect patients, and the direction of this influence (i.e., an increase or decrease of neglect severity) was modulated by the integrity of the right optic radiation. In patients with an intact optic radiation, the severity of neglect significantly decreased in the dynamic condition. Conversely, in patients with damage to the optic radiation, the severity of neglect significantly increased in the dynamic condition. CONCLUSION: Motion may influence neglect in stroke patients. The integrity of the optic radiation may be a predictor of whether motion increases or decreases the severity of neglect symptoms. PMID- 26158620 TI - Endothelial Functioning and Hemodynamic Parameters in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement. AB - OBJECTIVE: Subclinical hypothyroidism (SCH) and its associations with atherosclerosis (AS) and cardiovascular disease remain controversial. The purpose of our study was to observe changes in endothelial functioning and hemodynamics in rats with SCH and to determine whether L-thyroxine (L-T4) administration affects these changes. METHODS: In total, sixty male Wistar rats were randomly divided into the following three groups with 20 rats each: control euthyroid rats, SCH rats and SCH rats that had been treated with thyroxine (SCH+T4). The SCH rats were induced by administration of 10 mg x kg(-1) x d(-1) methimazole (MMI) once daily by gavage for 3 months. The SCH+T4 rats were administered the same dose of MMI for three months in addition to 2 MUg x kg(-1) x d(-1) L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage. RESULTS: The SCH group had significantly higher thyroid-stimulating hormone (TSH), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and endothelin (ET) levels and a lower nitric oxide (NO) level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure, heart rate and aorta ventralis blood flow were significantly lower in the SCH group than in the control and SCH+T4 groups. ACH treatment caused concentration-dependent relaxation, which was reduced in the SCH arteries compared with the control and SCH+T4 arteries. Histopathological examination revealed the absence of pathological changes in the SCH rat arteries. CONCLUSIONS: These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats. PMID- 26158622 TI - Optimal vaccination program for healthy adults in China. AB - There is still no suitable routine hepatitis B immunization strategy for adults in China. To establish an optimal vaccination schedule for healthy adults, we investigated various schedules in healthy adults. In this randomized 5143 healthy adults received 10 MUg hepatitis B vaccine at 0, 1 and 3 months(group A), 0, 1 and 6 months(group B), or 0, 1 and 12 months(group C). Blood samples were collected after 1 month and 12 months after the third dose. The geometric mean titer (GMT), seroconversion rate (levels of anti-HBs >= 10 mIU/mL) and high response rate (levels of anti-HBs >= 100 mIU/mL) were assayed. In our study, 2438 healthy adults finished the full vaccination program and follow-up. The seroconversion/sero-protective rate of groups A-C at one and 12 month after administration of the third vaccine dose was 100%, 99.9% and 97.9% verse 64.9%, 75.7% and 79.0%, respectively. GMT for anti-HBs tested in group A to C within 1 or 12 month after the third vaccination was 213.16, 432.58 and 451.47 mIU/ml verse 22.07, 46.70 and 56.18 mIU/ml, respectively. There were significant differences of seroconversion/sero-protective rate and GMT among the 3 groups (p < 0.01). Given the high anti-HBs seroconversion rate and GMT in all 3 groups, a flexible schedule for Hepatitis B vaccine should be recommended to adults, but 0 1-12 schedule is a better choice. PMID- 26158624 TI - Kinetico-mechanistic studies on the formation of seven-membered [C,N] platinacycles: the effect of methyl or fluoro substituents on the aryl ancillary ligands. AB - The reactions of dinuclear [Pt2(4-RC6H4)4(MU-SEt2)2] (R = Me or F), or mononuclear [Pt(4-RC6H4)2(SMe2)2] (R = Me or H), platinum(ii) compounds with imines of the general formula 2-X,6-YC6H3CH[double bond, length as m-dash]NCH2Ph (X = Br, Y = F; X = Cl, Y = F; X = Br, Y = H) produced seven-membered [C,N] platinacycles. The reaction consists of the initial formation of cyclometallated platinum(iv) compounds followed by a three step process: reductive elimination, isomerisation of the resulting non-cyclometallated intermediate and a final cycloplatination process. Combined (1)H NMR and UV-Vis kinetico-mechanistic studies indicated that the rate determining step of the process depends on the nature of the aryl-Pt ligand (phenyl, p-tolyl or p-fluorophenyl). PMID- 26158625 TI - [Antibiotic Resistance - The Last Stand[Editorial]]. PMID- 26158621 TI - Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors. AB - Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5 HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties. PMID- 26158623 TI - A drug-specific nanocarrier design for efficient anticancer therapy. AB - The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery. PMID- 26158626 TI - [Ms. Ragnheidur - Harm Reduction in Reykjavik]. PMID- 26158627 TI - [Outcome of surgical treatment for Pancoast lung carcinoma in Iceland]. AB - OBJECTIVE: Pancoast tumors are lung carcinomas that invade the apical chest wall and surrounding structures. Treatment is complex and often involves surgery together with radio- and chemotherapy. We studied the outcome of surgical resection for Pancoast tumors in Iceland. MATERIALS AND METHODS: A retrospective study including all patients that underwent resection of a Pancoast tumor with curative intent in Iceland in the years 1991-2010. Data on symptoms, complications, TNM-stage, relapse and survival were analyzed. RESULTS: Twelve patients were operated on; 7 on the right lung. Shoulder pain (n=5) and/or chest pain (n=3), cough (n=6) and weight loss (n=5) were the most common presenting symptoms. Adenocarcinoma (n=5) and squamous cell carcinoma (n=4) were the most frequent histological types. Average tumor size was 5,9 cm (range: 2,8-15). Five cases were stage IIB and 7 stage IIIA according to operative staging. In 10 cases (83%) the surgical margins were free of tumor. All patients survived surgery and only one patient suffered a major operative complication, an intraoperative bleeding. In one case induction chemo-radiation prior to surgery was administrated, and 8 patients received postoperative radiotherapy. Recurrent disease was diagnosed in 9 patients; four had local or regional recurrence, four had distant metastases and one patient was diagnosed with both local and distant recurrences simultaneously. Survival at 5 years was 33% and median survival was 27,5 months (range: 4-181). CONCLUSIONS: Operative and short-term outcomes for patients with Pancoast tumors in Iceland are excellent. However, long-term outcomes are not as favorable and recurrence rate is high compared to other studies, possibly due to incomplete preoperative staging and less use of chemo radiation therapy prior to surgery among these patients. PMID- 26158628 TI - [Acute exacerbations of chronic obstructive pulmonary disease - review]. AB - Chronic obstructive pulmonary disease is common and is associated with high morbidity and mortality. It leads to huge costs in the health care system. One of the reasons is acute exacerbations that lead to hospital admissions, increased medication use and other costly operations. They can also lead to death. In this review we will discuss the definition of acute exacerbation, causes and differential diagnosis. Treatment will be discussed and ways to avoid repeated exacerbations. Among ways to prevent acute exacerbations is drug treatment such as inhaled long-acting bronchodilators, inhaled corticosteroids and combination treatment. In selected cases antibiotics and antioxidants can be helpful. Influenza and pneumococcal vaccinations are important in addition to pulmonary rehabilitation. It is important to evaluate the role of co-morbidities and treat those diseases also. Examples of comorbidites are coronary artery disease and heart failure but also anxiety and depression. PMID- 26158629 TI - [Acute ischemic stroke in female adolescent - Case report]. AB - During soccer practice a fifteen year old girl experienced a sudden onset of pain in the left side of her neck and collapsed. Upon arrival at the emergency room she had right hemiparesis and expressive aphasia. On CT angiography a left carotid arterial dissection was suspected. Symptoms improved during the first three days but worsened again on the fourth and a CT scan showed an ischemic area in the brain. Conventional angiography showed decreased perfusion in the left middle cerebral artery but no evidence of dissection or thrombus. The most likely diagnosis was thought to be reverse cerebral vasoconstriction syndrome and the girl was treated with calcium channel inhibitors. Here we report the case and review the literature. PMID- 26158630 TI - Crucial roles of RSK in cell motility by catalysing serine phosphorylation of EphA2. AB - Crosstalk between inflammatory signalling pathways and receptor tyrosine kinases has been revealed as an indicator of cancer malignant progression. In the present study, we focus on EphA2 receptor tyrosine kinase, which is overexpressed in many human cancers. It has been reported that ligand-independent phosphorylation of EphA2 at Ser-897 is induced by Akt. We show that inflammatory cytokines promote RSK-, not Akt-, dependent phosphorylation of EphA2 at Ser-897. In addition, the RSK-EphA2 signalling pathway controls cell migration and invasion of metastatic breast cancer cells. Moreover, Ser-897-phosphorylated EphA2 co-localizes with phosphorylated active form of RSK in various human tumour specimens, and this double positivity is related to poor survival in lung cancer patients, especially those with a smoking history. Taken together, these results indicate that the phosphorylation of EphA2 at Ser-897 is controlled by RSK and the RSK-EphA2 axis might contribute to cell motility and promote tumour malignant progression. PMID- 26158633 TI - Altered expression of circadian clock genes during peripheral blood stem cell mobilization induced by granulocyte colony-stimulating factor. AB - Circulating hematopoietic stem cells exhibit robust circadian fluctuations, which influence the mobilized cell yield, even during enforced stem cell mobilization. However, alterations in the expression of circadian clock genes during granulocyte colony-stimulating factor (G-CSF)-induced peripheral blood stem cell (PBSC) mobilization are not fully elucidated. Therefore, we measured the expression of these genes in human peripheral blood leukocytes from 21 healthy donors. While CRY1 mRNA expression significantly increased by 3.9-fold (p < 0.01), the expression of PER3, CRY2 and BMAL1 mRNAs significantly decreased (by 0.2-fold, 0.2-fold, and 0.6-fold, respectively; p < 0.001) after G-CSF administration. Moreover, CRY1 mRNA expression was inversely correlated with the plasma level of noradrenaline (r = -0.36, p < 0.05), while PER3, CRY2, and BMAL1 mRNA expression directly correlated with the plasma level of noradrenaline (r = 0.55, r = 0.66, and r = 0.57, respectively; p < 0.001). Thus, significant correlations between the levels of circadian clock gene mRNAs and the plasma level of noradrenaline, a sympathetic nervous system neurotransmitter, were established. The modulation of sympathetic activation and of the circadian clock may be novel therapeutic targets for increasing stem cell yields in PBSC donors. PMID- 26158634 TI - A new "sweet" ligand for Toll-like receptor 4. PMID- 26158631 TI - TORC1 Inhibition by Rapamycin Promotes Antioxidant Defences in a Drosophila Model of Friedreich's Ataxia. AB - Friedreich's ataxia (FRDA), the most common inherited ataxia in the Caucasian population, is a multisystemic disease caused by a significant decrease in the frataxin level. To identify genes capable of modifying the severity of the symptoms of frataxin depletion, we performed a candidate genetic screen in a Drosophila RNAi-based model of FRDA. We found that genetic reduction in TOR Complex 1 (TORC1) signalling improves the impaired motor performance phenotype of FRDA model flies. Pharmacologic inhibition of TORC1 signalling by rapamycin also restored this phenotype and increased the lifespan and ATP levels. Furthermore, rapamycin reduced the altered levels of malondialdehyde + 4-hydroxyalkenals and total glutathione of the model flies. The rapamycin-mediated protection against oxidative stress is due in part to an increase in the transcription of antioxidant genes mediated by cap-n-collar (Drosophila ortholog of Nrf2). Our results suggest that autophagy is indeed necessary for the protective effect of rapamycin in hyperoxia. Rapamycin increased the survival and aconitase activity of model flies subjected to high oxidative insult, and this improvement was abolished by the autophagy inhibitor 3-methyladenine. These results point to the TORC1 pathway as a new potential therapeutic target for FRDA and as a guide to finding new promising molecules for disease treatment. PMID- 26158635 TI - KLF 6: a mitochondrial regulator in the kidney. PMID- 26158636 TI - N6-methyladenine: a potential epigenetic mark in eukaryotes. PMID- 26158637 TI - Effector Tregs: middle-men in TGFbeta activation. PMID- 26158638 TI - A nuclear sensor of mitochondrial function. PMID- 26158640 TI - Long-Term Care Services in the United States: 2013 Overview. AB - Long-term care services include a broad range of services that meet the needs of frail older people and other adults with functional limitations. Long-Term care services provided by paid, regulated providers are a significant component of personal health care spending in the United States. This report presents descriptive results from the first wave of the National Study of Long-Term Care Providers (NSLTCP), which was conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics (NCHS). Data presented in this report are drawn from five sources: NCHS surveys of adult day services centers and residential care communities, and administrative records obtained from the Centers for Medicare and Medicaid Services on home health agencies, hospices, and nursing homes. This report provides information on the supply, organizational characteristics, staffing, and services offered by providers of long-term care services; and the demographic, health, and functional composition of users of these services. Service users include residents of nursing homes and residential care communities, patients of home health agencies and hospices, and participants of adult day services centers. PMID- 26158641 TI - Detection of Binding Site Molecular Interaction Field Similarities. AB - Protein binding-site similarity detection methods can be used to predict protein function and understand molecular recognition, as a tool in drug design for drug repurposing and polypharmacology, and for the prediction of the molecular determinants of drug toxicity. Here, we present IsoMIF, a method able to identify binding site molecular interaction field similarities across protein families. IsoMIF utilizes six chemical probes and the detection of subgraph isomorphisms to identify geometrically and chemically equivalent sections of protein cavity pairs. The method is validated using six distinct data sets, four of those previously used in the validation of other methods. The mean area under the receiver operator curve (AUC) obtained across data sets for IsoMIF is higher than those of other methods. Furthermore, while IsoMIF obtains consistently high AUC values across data sets, other methods perform more erratically across data sets. IsoMIF can be used to predict function from structure, to detect potential cross reactivity or polypharmacology targets, and to help suggest bioisosteric replacements to known binding molecules. Given that IsoMIF detects spatial patterns of molecular interaction field similarities, its predictions are directly related to pharmacophores and may be readily translated into modeling decisions in structure-based drug design. IsoMIF may in principle detect similar binding sites with distinct amino acid arrangements that lead to equivalent interactions within the cavity. The source code to calculate and visualize MIFs and MIF similarities are freely available. PMID- 26158639 TI - Preparation and Characterization of Naringenin-Loaded Elastic Liposomes for Topical Application. AB - Excessive production of radical oxygen species in skin is a contributor to a variety of skin pathologies. Naringenin is a potent antioxidant. The purpose of the present study was to develop elastic liposomes for naringenin topical application. Naringenin-loaded elastic liposomes containing different amounts of Tween 80 and cholesterol were prepared. The physicochemical properties including vesicle size, surface charge, encapsulation efficiency, and permeability capacity were determined to evaluate the effect of components. The stability of formulation and skin irritation caused by drug-loaded elastic liposomes were also evaluated for assessment of the clinical utility of elastic liposomes. Saturated aqueous solution of naringenin and naringenin dissolved in 10% Tween 80 solution (5 mg/mL) were used as the control group. The result showed that in using elastic liposomes as carrier, the deposition amounts in the skin of naringenin were significantly increased about 7.3~11.8-fold and 1.2~1.9-fold respectively, when compared with the saturated aqueous solution and Tween 80 solution-treated groups. The level of drug was more than 98.89+/-3.90% after 3 months of storage at 4C. In a skin irritation test, the result showed experimental formulation exhibit considerably less irritating than the positive control (paraformaldehyde treated) group, suggesting its potential therapeutic application. PMID- 26158643 TI - Retraction. PMID- 26158642 TI - Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders. AB - BACKGROUND: Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease. METHODS: Clinical and pathologic data were reviewed as part of a Johns Hopkins-based natural history study of short telomere syndromes including dyskeratosis congenita. RESULTS: Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21%). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P < .001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed. CONCLUSIONS: This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting. PMID- 26158644 TI - Fine Tuning of a Type 1 Interferon Antagonist. AB - Type I interferons are multi-potent cytokines that serve as first line of defense against viruses and other pathogens, posses immunomudolatory functions and elicit a growth inhibitory response. In recent years it has been shown that interferons are also detrimental, for example in lupus, AIDS, tuberculosis and cognitive decline, highlighted the need to develop interferon antagonists. We have previously developed the antagonist IFN-1ant, with much reduced binding to the IFNAR1 receptor and enhanced binding to IFNAR2. Here, we further tune the IFN 1ant by producing three additional antagonists based on IFN-1ant but with altered activity profiles. We show that in all three cases the antiproliferative activity of interferons is blocked and the induction of gene transcription of immunomudolatory and antiproliferative associated genes are substantially decreased. Conversely, each of the new antagonists elicits a different degree of antiviral response, STAT phosphorylation and related gene induction. Two of the new antagonists promote decreased activity in relation to the original IFN-1ant, while one of them promotes increased activity. As we do not know the exact causes of the detrimental effects of IFNs, the four antagonists that were produced and analyzed provide the opportunity to investigate the extent of antagonistic and agonistic activity optimal for a given condition. PMID- 26158645 TI - Synthesis of quasi-free-standing bilayer graphene nanoribbons on SiC surfaces. AB - Scaling graphene down to nanoribbons is a promising route for the implementation of this material into devices. Quantum confinement of charge carriers in such nanostructures, combined with the electric field-induced break of symmetry in AB stacked bilayer graphene, leads to a band gap wider than that obtained solely by this symmetry breaking. Consequently, the possibility of fabricating AB-stacked bilayer graphene nanoribbons with high precision is very attractive for the purposes of applied and basic science. Here we show a method, which includes a straightforward air annealing, for the preparation of quasi-free-standing AB bilayer nanoribbons with different widths on SiC(0001). Furthermore, the experiments reveal that the degree of disorder at the edges increases with the width, indicating that the narrower nanoribbons are more ordered in their edge termination. In general, the reported approach is a viable route towards the large-scale fabrication of bilayer graphene nanostructures with tailored dimensions and properties for specific applications. PMID- 26158646 TI - Improving anterior deltoid activity in a musculoskeletal shoulder model - an analysis of the torque-feasible space at the sternoclavicular joint. AB - Modelling the shoulder's musculature is challenging given its mechanical and geometric complexity. The use of the ideal fibre model to represent a muscle's line of action cannot always faithfully represent the mechanical effect of each muscle, leading to considerable differences between model-estimated and in vivo measured muscle activity. While the musculo-tendon force coordination problem has been extensively analysed in terms of the cost function, only few works have investigated the existence and sensitivity of solutions to fibre topology. The goal of this paper is to present an analysis of the solution set using the concepts of torque-feasible space (TFS) and wrench-feasible space (WFS) from cable-driven robotics. A shoulder model is presented and a simple musculo-tendon force coordination problem is defined. The ideal fibre model for representing muscles is reviewed and the TFS and WFS are defined, leading to the necessary and sufficient conditions for the existence of a solution. The shoulder model's TFS is analysed to explain the lack of anterior deltoid (DLTa) activity. Based on the analysis, a modification of the model's muscle fibre geometry is proposed. The performance with and without the modification is assessed by solving the musculo tendon force coordination problem for quasi-static abduction in the scapular plane. After the proposed modification, the DLTa reaches 20% of activation. PMID- 26158648 TI - Temporal Coordination of Carbohydrate Metabolism during Mosquito Reproduction. AB - Hematophagous mosquitoes serve as vectors of multiple devastating human diseases, and many unique physiological features contribute to the incredible evolutionary success of these insects. These functions place high-energy demands on a reproducing female mosquito, and carbohydrate metabolism (CM) must be synchronized with these needs. Functional analysis of metabolic gene profiling showed that major CM pathways, including glycolysis, glycogen and sugar metabolism, and citrate cycle, are dramatically repressed at post eclosion (PE) stage in mosquito fat body followed by a sharply increase at post-blood meal (PBM) stage, which were also verified by Real-time RT-PCR. Consistent to the change of transcript and protein level of CM genes, the level of glycogen, glucose and trehalose and other secondary metabolites are also periodically accumulated and degraded during the reproductive cycle respectively. Levels of triacylglycerols (TAG), which represent another important energy storage form in the mosquito fat body, followed a similar tendency. On the other hand, ATP, which is generated by catabolism of these secondary metabolites, showed an opposite trend. Additionally, we used RNA interference studies for the juvenile hormone and ecdysone receptors, Met and EcR, coupled with transcriptomics and metabolomics analyses to show that these hormone receptors function as major regulatory switches coordinating CM with the differing energy requirements of the female mosquito throughout its reproductive cycle. Our study demonstrates how, by metabolic reprogramming, a multicellular organism adapts to drastic and rapid functional changes. PMID- 26158650 TI - Liquid levothyroxine and its potential use. PMID- 26158649 TI - Inhaled Pharmacotherapy and Stroke Risk in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Population Based Study Using Two-Stage Approach. AB - BACKGROUND AND PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) are at higher risk of stroke than those without COPD. This study aims to explore the impact of inhaled pharmacotherapy on stroke risk in COPD patients during a three-year follow-up, using a nationwide, population-based study and a matched cohort design. METHODS: The study cohort comprised 10,413 patients who had received COPD treatment between 2004 and 2006; 41,652 randomly selected subjects comprised the comparison cohort. Cox proportional hazard regressions and two-stage propensity score calibration were performed to determine the impact of various inhaled therapies including short-acting muscarinic antagonists, long acting muscarinic antagonists, short-acting beta-agonists (SABAs), long-acting beta-agonists (LABAs), and LABA plus inhaled corticosteroid (ICS), on the risk after adjustment for patient demographic characteristics and comorbid disorders. RESULTS: Of the 52,065 sampled patients, 2,689 (5.2%) developed stroke during follow-up, including 727 (7.0%) from the COPD cohort and 1,962 (4.7%) from the comparison cohort (p < 0.001). Treatment with SABA was associated with 1.67-fold (95% CI 1.45-1.91; p < 0.001) increased risk of stroke in COPD patients. By contrast, the cumulative incidence of stroke was significantly lower in those treated with LABA plus ICS than those treated without (adjusted hazard ratio 0.75, 95% CI 0.60-0.94, p = 0.014). CONCLUSIONS: Among COPD patients, the use of inhaled SABA is associated with an increased risk of stroke, and combination treatment with inhaled LABA and ICS relates to a risk reduction. Further prospective research is needed to verify whether LABA plus ICS confers protection against stroke in patients with COPD. PMID- 26158651 TI - Androgens as double-edged swords: Induction and suppression of follicular development. AB - Androgens, which are mediated via the androgen receptor (AR), play important roles in normal follicular development and female fertility. However, just like a double-edged sword, besides the positive effects of androgen on follicular development, abnormal androgen levels, especially as in hyperandrogenism, seriously suppress normal follicular development. A crucial balance exists between the importance of androgens in follicular development and their negative effects when in excess. As the first meiotic division and epigenetic reprogramming are two critical events in oogenesis, abnormal androgen levels or deficiency in androgen/AR signaling in the ovary may affect these vital events. Oocytes have a tendency to develop genomic instability, thus resulting in an increasing incidence of unpredictable adult diseases. Although many studies have explored the effects of androgens and AR on follicular development, the conclusions are controversial and there has been no thorough review of this topic. This review focuses on the roles of androgens in the physiological process of follicular development, summarizes new insights into the roles of androgens in the arrested development of follicles, and discusses the potential risk of adult diseases originating from abnormal follicular androgen levels or androgen receptor signals, which may determine areas for future studies. PMID- 26158652 TI - Primary hyperparathyroidism and the road to surgery: appraisal of the proceedings of the four international workshops (1990, 2002, 2008, 2014) on primary hyperparathyroidism. AB - Although surgery is unambiguously recommended for symptomatic primary hyperparathyroidism (PHPT) patients, management options for asymptomatic patients have varied between surgery, medications and follow-up. To deal with this issue, four International Workshops have taken place, in 1990, 2002, 2008 and 2014, during which a team of experts drew up criteria to stratify asymptomatic patients as surgery-eligible and surgery-ineligible. The efficacy of the criteria have however been questioned over the years and the majority of patients, both eligible and ineligible, may eventually have undergone surgery. Nevertheless, the criteria are still in use today and they clearly mirror the course of change in the treatment of PHPT patients. PMID- 26158653 TI - Pregnancy-Induced hypertension. AB - Pregnancy-induced hypertension (PIH) complicates 6-10% of pregnancies. It is defined as systolic blood pressure (SBP) >140 mmHg and diastolic blood pressure (DBP) >90 mmHg. It is classified as mild (SBP 140-149 and DBP 90-99 mmHg), moderate (SBP 150-159 and DBP 100-109 mmHg) and severe (SBP >= 160 and DBP >= 110 mmHg). PIH refers to one of four conditions: a) pre-existing hypertension, b) gestational hypertension and preeclampsia (PE), c) pre-existing hypertension plus superimposed gestational hypertension with proteinuria and d) unclassifiable hypertension. PIH is a major cause of maternal, fetal and newborn morbidity and mortality. Women with PIH are at a greater risk of abruptio placentae, cerebrovascular events, organ failure and disseminated intravascular coagulation. Fetuses of these mothers are at greater risk of intrauterine growth retardation, prematurity and intrauterine death. Ambulatory blood pressure monitoring over a period of 24 h seems to have a role in predicting deterioration from gestational hypertension to PE. Antiplatelet drugs have moderate benefits when used for prevention of PE. Treatment of PIH depends on blood pressure levels, gestational age, presence of symptoms and associated risk factors. Non-drug management is recommended when SBP ranges between 140-149 mmHg or DBP between 90-99 mmHg. Blood pressure thresholds for drug management in pregnancy vary between different health organizations. According to 2013 ESH/ESC guidelines, antihypertensive treatment is recommended in pregnancy when blood pressure levels are >= 150/95 mmHg. Initiation of antihypertensive treatment at values >= 140/90 mmHg is recommended in women with a) gestational hypertension, with or without proteinuria, b) pre-existing hypertension with the superimposition of gestational hypertension or c) hypertension with asymptomatic organ damage or symptoms at any time during pregnancy. Methyldopa is the drug of choice in pregnancy. Atenolol and metoprolol appear to be safe and effective in late pregnancy, while labetalol has an efficacy comparable to methyldopa. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists are contraindicated in pregnancy due to their association with increased risk of fetopathy. PMID- 26158654 TI - Maternal vitamin D status in pregnancy: a critical appraisal of current analytical data on maternal and neonatal outcomes. AB - Maternal hypovitaminosis D during pregnancy has been associated with a wide spectrum of adverse maternal and neonatal health outcomes, some manifesting stronger associations than others. Research in this field has entered the "era of systematic data evaluation" via the conducting of a series of meta-analyses in an attempt to synthesize the diverse data from observational and supplementation studies. The aim of this review was to provide a critical appraisal of published observational and interventional (supplementation) meta-analyses on the link between maternal vitamin D status and health consequences to both mothers and neonates. A literature review was performed by two reviewers in the Medline and Embase databases, from inception to March 2014, without any language restriction. Additional articles were identified by a manual search of the references from the key articles retrieved. The results provided evidence that the meta-analyses on the link between maternal vitamin D status and maternal / neonatal health consequences are characterized by a wide heterogeneity of studied populations as well as methodological pitfalls, including the absence of standardized vitamin D assays and evaluation of vital external regulators of vitamin D bio-networks. Based on the above, interpretation of these meta-analyses should be carried out with care. Future supplementation studies should take into consideration all these population and methodological issues by incorporating them in their research design and settings. PMID- 26158655 TI - Obesity, but not polycystic ovary syndrome, affects circulating markers of low grade inflammation in young women without major cardiovascular risk factors. AB - OBJECTIVE: The aim of this study was to evaluate the influence of polycystic ovary syndrome (PCOS) and obesity on circulating markers of low-grade inflammation-tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and high sensitive C-reactive protein (hsCRP)-in young women without major cardiovascular (CV) risk factors (diabetes, dyslipidemia and arterial hypertension). DESIGN: Twenty-five young women with PCOS and 23 eumenorrheic women without major CV risk factors and matched for body mass index (BMI) were studied. They were subdivided according to BMI and PCOS status and comparisons were made between the PCOS and Control groups, regardless of BMI, and between the Obese and Lean groups, regardless of the presence of PCOS. RESULTS: Levels of TNF alpha, IL-6 and hsCRP were similar between the PCOS group and the Control group (2.1 vs 1.9 pg/ml, p=0.397, 3.8 vs 5.7 pg/ml, p=0.805 and 0.9 vs 0.5 ng/ml, p=0.361, respectively). Levels of TNF-alpha were similar between the obese group and the lean group (2.1 vs 1.9 pg/ml, p=0.444). Levels of IL-6 and hsCRP were higher in the obese group than in the lean group (8.7 vs 2.0, p <0.001 and 1.4 vs 0.2 ng/ml, p <0.001, respectively). CONCLUSION: Obesity, but not polycystic ovary syndrome, affects circulating markers of low-grade inflammation in young women without major CV risk factors. PMID- 26158656 TI - Familial partial lipodystrophy type 3: a new mutation on the PPARG gene. PMID- 26158657 TI - A novel mutation of the calcium-sensing receptor gene in a Greek family from Nisyros. AB - PURPOSE: Inactivating mutations of the calcium-sensing receptor (CASR) gene cause familial hypocalciuric hypercalcaemia (FHH). Here we report three siblings with FHH caused by a novel mutation in the CASR. METHODS: The case subject was a 60 year-old patient referred because of mild hypercalcaemia, increased PTH levels and persistently low calcium/creatinine ratio. FHH was suspected and a family biochemical and genetic analysis was performed. RESULTS: Sequencing of the CASR gene revealed a frameshift mutation (Val258Arg) in the extracellular domain of the CASR that creates a premature 46 amino acids stop codon which leads to a truncated protein that might affect its function. This heterozygous loss-of function mutation in the CaSR gene causes reduced CaSR sensing ability resulting in the clinical manifestation of FHH. CONCLUSION: We hereby report the identification of a novel heterozygous loss-of-function mutation of the CASR gene in a Greek family from Nisyros island. Functional studies are needed to clarify the exact role of this mutation in CASR activity. PMID- 26158658 TI - History of the Cretan cohort of the Seven Countries Study. PMID- 26158659 TI - Considering psychoeducation on structural dissociation for dialectical behavior therapy patients experiencing high-risk dissociative behaviors. AB - Dialectical behavioral therapy (DBT) programs, particularly for low-functioning individuals at the safety and stabilization phase of therapy, work with a variety of high-risk and often complex cases, with a curriculum consisting primarily of concrete skill acquisition and application. A significant subset of individuals in DBT programs, however, may suffer high-risk dissociative episodes in which skill application may be less available to them, contributing to further destabilization, demoralization, and thoughts of self-inefficacy in treatment. This article evaluates the potential benefits of complementing traditional DBT with psychoeducation on structural dissociation for such patients, acknowledging and addressing some of the concerns that might accompany such a consideration. PMID- 26158660 TI - Scale-Free Navigational Planning by Neuronal Traveling Waves. AB - Spatial navigation and planning is assumed to involve a cognitive map for evaluating trajectories towards a goal. How such a map is realized in neuronal terms, however, remains elusive. Here we describe a simple and noise-robust neuronal implementation of a path finding algorithm in complex environments. We consider a neuronal map of the environment that supports a traveling wave spreading out from the goal location opposite to direction of the physical movement. At each position of the map, the smallest firing phase between adjacent neurons indicate the shortest direction towards the goal. In contrast to diffusion or single-wave-fronts, local phase differences build up in time at arbitrary distances from the goal, providing a minimal and robust directional information throughout the map. The time needed to reach the steady state represents an estimate of an agent's waiting time before it heads off to the goal. Given typical waiting times we estimate the minimal number of neurons involved in the cognitive map. In the context of the planning model, forward and backward spread of neuronal activity, oscillatory waves, and phase precession get a functional interpretation, allowing for speculations about the biological counterpart. PMID- 26158661 TI - Dimensional Crossover of Thermal Transport in Hybrid Boron Nitride Nanostructures. AB - Although boron nitride nanotubes (BNNT) and hexagonal-BN (hBN) are superb one dimensional (1D) and 2D thermal conductors respectively, bringing this quality into 3D remains elusive. Here, we focus on pillared boron nitride (PBN) as a class of 3D BN allotropes and demonstrate how the junctions, pillar length and pillar distance control phonon scattering in PBN and impart tailorable thermal conductivity in 3D. Using reverse nonequilibrium molecular dynamics simulations, our results indicate that although a clear phonon scattering at the junctions accounts for the lower thermal conductivity of PBN compared to its parent BNNT and hBN allotropes, it acts as an effective design tool and provides 3D thermo mutable features that are absent in the parent structures. Propelled by the junction spacing, while one geometrical parameter, e.g., pillar length, controls the thermal transport along the out-of-plane direction of PBN, the other parameter, e.g., pillar distance, dictates the gross cross-sectional area, which is key for design of 3D thermal management systems. Furthermore, the junctions have a more pronounced effect in creating a Kapitza effect in the out-of-plane direction, due to the change in dimensionality of the phonon transport. This work is the first report on thermo-mutable properties of hybrid BN allotropes and can potentially impact thermal management of other hybrid 3D BN architectures. PMID- 26158662 TI - Reconciliation of Decision-Making Heuristics Based on Decision Trees Topologies and Incomplete Fuzzy Probabilities Sets. AB - Complex decision making tasks of different natures, e.g. economics, safety engineering, ecology and biology, are based on vague, sparse, partially inconsistent and subjective knowledge. Moreover, decision making economists / engineers are usually not willing to invest too much time into study of complex formal theories. They require such decisions which can be (re)checked by human like common sense reasoning. One important problem related to realistic decision making tasks are incomplete data sets required by the chosen decision making algorithm. This paper presents a relatively simple algorithm how some missing III (input information items) can be generated using mainly decision tree topologies and integrated into incomplete data sets. The algorithm is based on an easy to understand heuristics, e.g. a longer decision tree sub-path is less probable. This heuristic can solve decision problems under total ignorance, i.e. the decision tree topology is the only information available. But in a practice, isolated information items e.g. some vaguely known probabilities (e.g. fuzzy probabilities) are usually available. It means that a realistic problem is analysed under partial ignorance. The proposed algorithm reconciles topology related heuristics and additional fuzzy sets using fuzzy linear programming. The case study, represented by a tree with six lotteries and one fuzzy probability, is presented in details. PMID- 26158663 TI - The Stroke Caregiver Unmet Resource Needs Scale: Development and Psychometric Testing. PMID- 26158664 TI - Introduction to the Special Issue: From Philosophical Thinking to Psychological Empiricism. PMID- 26158665 TI - Free Will in Scientific Psychology. AB - Some actions are freer than others, and the difference is palpably important in terms of inner process, subjective perception, and social consequences. Psychology can study the difference between freer and less free actions without making dubious metaphysical commitments. Human evolution seems to have created a relatively new, more complex form of action control that corresponds to popular notions of free will. It is marked by self-control and rational choice, both of which are highly adaptive, especially for functioning within culture. The processes that create these forms of free will may be biologically costly and therefore are only used occasionally, so that people are likely to remain only incompletely self-disciplined, virtuous, and rational. PMID- 26158666 TI - Why Heuristics Work. AB - The adaptive toolbox is a Darwinian-inspired theory that conceives of the mind as a modular system that is composed of heuristics, their building blocks, and evolved capacities. The study of the adaptive toolbox is descriptive and analyzes the selection and structure of heuristics in social and physical environments. The study of ecological rationality is prescriptive and identifies the structure of environments in which specific heuristics either succeed or fail. Results have been used for designing heuristics and environments to improve professional decision making in the real world. PMID- 26158667 TI - Schizophrenia. AB - Theoretical conceptualizations of schizophrenia have undergone significant change in the past century. Through the application of behavioral science methodology, psychologists have played a major role in the pivotal scientific advances that have led us to contemporary models. The field has moved from simplistic conceptualizations of mind-brain distinctions to models that encompass complex gene-environment interactions and neural pathways that mediate the relation between psychosocial events and brain dysfunction. PMID- 26158668 TI - Language: A Toolbox for Sharing and Influencing Social Reality. AB - The key role of language is often neglected in explicitly formulated theories of cognition, affect, and social behavior. Implicitly, though, the relationship between language and mind is at the heart of psychological science. Two major research programs-linguistic universals and linguistic relativity-originate in opposite philosophical positions, assuming either that language reflects the mind's ideas and free will or that language differences govern and restrict the mind. However, modern psychological research was able to begin illuminating the power and richness of linguistic influences only after the priority debate was given up and language and cognition were treated as integral parts of the same process. Beyond the confines of referential communication, conceived as cooperative transfer of symbols referring to common world knowledge, some of the most intriguing phenomena are detached from referential bonds, reflecting unintended, emergent, or even random outcomes of verbal interaction. Indeed, the effectiveness of verbal priming may be actually contingent on language users failure to understand the primes referential meanings and implications. PMID- 26158669 TI - Understanding the Vital Human Quest for Self-Esteem. AB - Authors have long noted the human penchant for self-esteem. Experimental research has revealed that this desire for self-esteem has wide-ranging effects on cognition, emotion, and behavior. Terror management theory explains that this desire for self-esteem results from a fundamental need for psychological security, which is engendered by humans' awareness of their own vulnerability and mortality. A large body of evidence has supported this explanation. Specifically, substantial lines of research have shown that self-esteem buffers anxiety and reduces defenses against death and that reminders of mortality increase efforts to defend and bolster self-esteem. Complementary findings have helped clarify the role of culture in self-esteem striving and the ways in which people can vary in their level, stability, and sources of self-esteem. I conclude by briefly considering how this contemporary knowledge regarding the quest for self-esteem informs current events and daily life. PMID- 26158670 TI - The Fascination of Wisdom: Its Nature, Ontogeny, and Function. AB - Wisdom has intrigued both scholars and laypersons since antiquity. On the one hand, its seemingly ethereal yet obvious qualities are timeless and universal. On the other hand, these same qualities are evolving and responsive to historical and cultural change. Novel societal and personal dilemmas emerge over time, and the ways and means to deal with recurring dilemmas are revisited and updated with prudence. Building on philosophical analyses of the role of theoretical and practical wisdom in good conduct and judgment about life matters, psychologists have begun to apply scientific methods to questions about the nature, function, and ontogeny of wisdom. We outline these research directions and focus on the Berlin Wisdom Paradigm, which was one of the first attempts to bring wisdom into the laboratory. Future research on wisdom would profit from interdisciplinary collaboration and creative application of new methods drawn from developmental, social, and cognitive psychology. PMID- 26158671 TI - Morality. AB - Moral psychology is a rapidly growing field with two principle lineages. The main line began with Jean Piaget and includes developmental psychologists who have studied the acquisition of moral concepts and reasoning. The alternative line began in the 1990s with a new synthesis of evolutionary, neurological, and social psychological research in which the central phenomena are moral emotions and intuitions. In this essay, I show how both of these lines have been shaped by an older debate between two 19th century narratives about modernity: one celebrating the liberation of individuals, the other mourning the loss of community and moral authority. I suggest that both lines of moral psychology have limited themselves to the moral domain prescribed by the liberation narrative, and so one future step for moral psychology should be to study alternative moral perspectives, particularly religious and politically conservative ones in which morality is, in part, about protecting groups, institutions, and souls. PMID- 26158672 TI - Love: What Is It, Why Does It Matter, and How Does It Operate? AB - Love is a perennial topic of fascination for scholars and laypersons alike. Whereas psychological science was slow to develop active interest in love, the past few decades have seen considerable growth in research on the subject, to the point where a uniquely psychological perspective on love can be identified. This article describes some of the more central and well-established findings from psychologically informed research on love and its influence in adult human relationships. We discuss research on how love is defined, the significance of love for human activity and well-being, and evidence about the mechanisms by which love is believed to operate. We conclude by describing several key questions and potentially important new directions for the next wave of psychological science. PMID- 26158673 TI - Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume. AB - Prostate enlargement leading to clinical benign prostatic hyperplasia (BPH) is associated with metabolic dysregulation and obesity. The genetic basis of this association is unclear. Our objective was to evaluate whether single nucleotide polymorphisms (SNPs) previously associated with metabolic disorders are also associated with prostate volume (PV). Participants included 876 men referred for prostate biopsy and found to be prostate cancer free. PV was measured by transrectal ultrasound. Samples were genotyped using the Illumina Cardio MetaboChip platform. Multivariable adjusted linear regression models were used to evaluate SNPs (additive coding) in relation to natural-log transformed (log) PV. We compared SNP-PV results from biopsy-negative men to 442 men with low-grade prostate cancer with similar levels of obesity and PV. Beta-coefficients from the discovery and replication samples were then aggregated with fixed effects inverse variance weighted meta-analysis. SNP rs11736129 (near the pseudo-gene LOC100131429) was significantly associated with log-PV (beta: 0.16, p-value 1.16x10(-8)) after adjusting for multiple testing. Other noteworthy SNPs that were nominally associated (p-value < 1x10(-4)) with log-PV included rs9583484 (intronic SNP in COL4A2), rs10146527 (intronic SNP in NRXN3), rs9909466 (SNP near RPL32P31), and rs2241606 (synonymous SNP in SLC12A7). We found several SNPs in metabolic loci associated with PV. Further studies are needed to confirm our results and elucidate the mechanism between these genetic loci, PV, and clinical BPH. PMID- 26158675 TI - Correction: Phosphorylation of Mouse Immunity-Related GTPase (IRG) Resistance Proteins Is an Evasion Strategy for Virulent Toxoplasma gondii. PMID- 26158674 TI - Rapid Quantification of 3D Collagen Fiber Alignment and Fiber Intersection Correlations with High Sensitivity. AB - Metastatic cancers aggressively reorganize collagen in their microenvironment. For example, radially orientated collagen fibers have been observed surrounding tumor cell clusters in vivo. The degree of fiber alignment, as a consequence of this remodeling, has often been difficult to quantify. In this paper, we present an easy to implement algorithm for accurate detection of collagen fiber orientation in a rapid pixel-wise manner. This algorithm quantifies the alignment of both computer generated and actual collagen fiber networks of varying degrees of alignment within 5 degrees degrees . We also present an alternative easy method to calculate the alignment index directly from the standard deviation of fiber orientation. Using this quantitative method for determining collagen alignment, we demonstrate that the number of collagen fiber intersections has a negative correlation with the degree of fiber alignment. This decrease in intersections of aligned fibers could explain why cells move more rapidly along aligned fibers than unaligned fibers, as previously reported. Overall, our paper provides an easier, more quantitative and quicker way to quantify fiber orientation and alignment, and presents a platform in studying effects of matrix and cellular properties on fiber alignment in complex 3D environments. PMID- 26158688 TI - External Oxidant-Free Oxidative Cross-Coupling: A Photoredox Cobalt-Catalyzed Aromatic C-H Thiolation for Constructing C-S Bonds. AB - An external oxidant-free oxidative coupling for aromatic C-H thiolation by visible-light photoredox cobalt-catalysis has been developed. Various substrates could afford benzothiazoles in good to excellent yields, and only H2 is generated as a side product. When catalytic TBAOH was used as the base, not only 2-aryl but also 2-alkylbenzothiazoles could be obtained through this novel dehydrogenative coupling reaction. This method could be scaled up and applied to the synthesis of biologically active molecules bearing benzothiazole structural scaffolds (potent antitumor agents). Furthermore, the unexpected oxidation byproduct amides, which are often generated in oxidative cyclization of thiobenzanilides, can be completely avoided. Mechanistic studies showed that the H2 originates from the substrates. The kinetic studies indicate that the interaction between the cobalt catalyst and proton might be involved in the rate-limiting process. PMID- 26158679 TI - Making Healthy Eating Policy Practice: A Group Randomized Controlled Trial on Changes in Snack Quality, Costs, and Consumption in After-School Programs. AB - PURPOSE: The aim of this study was to evaluate an intervention designed to assist after-school programs (ASPs) in meeting snack nutrition policies that specify that a fruit or vegetable be served daily and sugar-sweetened beverages/foods and artificially flavored foods eliminated. DESIGN: The study used a 1-year group randomized controlled trial. SETTING: The study took place in ASPs operating in South Carolina, United States. SUBJECTS: Twenty ASPs serving over 1700 children were recruited, match-paired postbaseline on enrollment size and days fruits/vegetables were served per week, and randomized to either intervention (n = 10) or control (n = 10) groups. INTERVENTION: The study used Strategies To Enhance Practice for Healthy Eating (STEPs-HE), a multistep adaptive intervention framework that assists ASP leaders and staff to serve snacks that meet nutrition policies while maintaining cost. MEASURES: Direct observation of snacks served and consumed and monthly snack expenditures as determined by receipts were used. ANALYSIS: The study used nonparametric and mixed-model repeated measures. RESULTS: By postassessment, intervention ASPs increased serving of fruits/vegetables to 3.9 +/- 2.1 vs. 0.7 +/- 1.7 d/wk and decreased serving sugar sweetened beverages to 0.1 +/- 0.7 vs. 1.8 +/- 2.4 d/wk and sugar-sweetened foods to 0.3 +/- 1.1 vs. 2.7 +/- 2.5 d/wk compared to controls, respectively. Cost of snacks increased by $0.02/snack in the intervention ASPs ($0.36 to $0.38) compared to a $0.01 per snack decrease in the control group ($0.39 to $0.38). Across both assessments and groups, 80% to 100% of children consumed FVs. CONCLUSIONS: The STEPs-HE intervention can assist ASPs in meeting nationally endorsed nutrition policies with marginal increases in cost. PMID- 26158689 TI - Disease burden of enterovirus 71 in rural central China: A community-based survey. AB - In recent years, the epidemics of hand, foot, and mouth disease (HFMD) centered in the Asian-Pacific region have been characterized by high morbidity and mortality. Enterovirus 71 (EV71) infections were responsible for the majority of the infections leading to severe cases of HFMD and death. This is a community based survey aimed to estimate the disease burden of EV71 in rural central China, especially for HFMD. From 2011 to 2013, demographic and socio-economic data were gathered from 343 ill children and their parents using a structured questionnaire. We quantified the health burden of disease resulting from EV71 infection in disability-adjusted life years (DALYs). Among 343 cases, 303 had confirmed HFMD, 6 presented with herpangina, 25 presented with respiratory symptoms, and 9 presented with non-specific symptoms. The number of severe cases was 47 (including 1 death) and all of these presented with HFMD. The total cost per patient for severe HFMD, mild HFMD, herpangina, respiratory disease, and non specific disease was $2149.47, $513.22, $53.28, $31.95, and $39.25, respectively. The overall cost of EV71-related diseases as a proportion of local farmers' per capita net income ranged from 0.18% for those with non-specific disease to 187.12% for those with severe HFMD. The loss of DALYs for the 5 forms of disease were 3.47, 1.76, 1.07, 1.44, 1.22 person-years per 1000 persons, respectively. This study provides data on cost of treatment and health burden for diseases caused by EV71, which can be used in the evaluation of EV71 vaccine cost effectiveness. PMID- 26158690 TI - Efficient Triplet-Triplet Annihilation-Based Upconversion for Nanoparticle Phototargeting. AB - High-efficiency upconverted light would be a desirable stimulus for triggered drug delivery. Here we present a general strategy to achieve photoreactions based on triplet-triplet annihilation upconversion (TTA-UC) and Forster resonance energy transfer (FRET). We designed PLA-PEG micellar nanoparticles containing in their cores hydrophobic photosensitizer and annihilator molecules which, when stimulated with green light, would undergo TTA-UC. The upconverted energy was then transferred by FRET to a hydrophobic photocleavable group (DEACM), also in the core. The DEACM was bonded to (and thus inactivated) the cell-binding peptide cyclo-(RGDfK), which was bound to the PLA-PEG chain. Cleavage of DEACM by FRET reactivated the PLA-PEG-bound peptide and allowed it to move from the particle core to the surface. TTA-UC followed by FRET allowed photocontrolled binding of cell adhesion with green light LED irradiation at low irradiance for short periods. These are attractive properties in phototriggered systems. PMID- 26158691 TI - Coming of Age: Gas-Phase Structural Information on Biomolecules by FRET. PMID- 26158693 TI - Iridium Oxide Nanoparticles and Iridium/Iridium Oxide Nanocomposites: Photochemical Fabrication and Application in Catalytic Reduction of 4 Nitrophenol. AB - Hydrous iridium oxide (IrOx) nanoparticles (NPs) with an average diameter of 1.7 +/- 0.3 nm were prepared via photochemical hydrolysis of iridium chloride in alkaline medium at room temperature. The photoinduced hydrolysis was monitored by time-dependent ultraviolet-visible (UV-vis) spectroscopy, and the effects of the incident wavelength and irradiation time on the production of IrOx NPs were systematically investigated. It was found that UV-vis irradiation is crucial for the generation of IrOx NPs during the hydrolysis of IrCl3, and once the irradiation was turned off, the hydrolysis reaction stopped immediately. The production rate of IrOx NPs greatly depended on the incident wavelength. There is a critical wavelength of 500 nm for the hydrolysis reaction, and IrOx NPs can only be produced under the illumination with an incident wavelength shorter than 500 nm. Moreover, the shorter the incident wavelength, the faster the growth rate of IrOx NPs. The obtained IrOx NPs were highly stable during two months of storage at 4 degrees C. The Ir/IrOx nanocomposites were prepared by surface reduction of IrOx NPs with NaBH4. The microstructure of the Ir/IrOx composite was characterized by transmission electron microscopy (TEM), and the presence of zero valence Ir was confirmed by the X-ray diffraction (XRD) result. The Ir/IrOx nanocomposite exhibited good catalytic activity and high recycling stability toward the reduction of 4-nitrophenol. The catalytic activity per unit surface area of the Ir/IrOx composite catalyst was increased by a factor of 15 compared to that of pure Ir catalyst. The presence of the Ir/IrOx interfaces in the composite catalyst is believed to be responsible for the high activity. PMID- 26158694 TI - Keeping Food on the Table: Human Responses and Changing Coastal Fisheries in Solomon Islands. AB - Globally the majority of commercial fisheries have experienced dramatic declines in stock and catch. Likewise, projections for many subsistence fisheries in the tropics indicate a dramatic decline is looming in the coming decades. In the Pacific Islands coastal fisheries provide basic subsistence needs for millions of people. A decline in fish catch would therefore have profound impacts on the health and livelihoods of these coastal communities. Given the decrease in local catch rates reported for many coastal communities in the Pacific, it is important to understand if fishers have responded to ecological change (either by expanding their fishing range and/or increasing their fishing effort), and if so, to evaluate the costs or benefits of these responses. We compare data from fish catches in 1995 and 2011 from a rural coastal community in Solomon Islands to examine the potentially changing coastal reef fishery at these time points. In particular we found changes in preferred fishing locations, fishing methodology and catch composition between these data sets. The results indicate that despite changes in catch rates (catch per unit effort) between data collected in 2011 and 16 years previously, the study community was able to increase gross catches through visiting fishing sites further away, diversifying fishing methods and targeting pelagic species through trolling. Such insight into local-scale responses to changing resources and/or fisheries development will help scientists and policy makers throughout the Pacific region in managing the region's fisheries in the future. PMID- 26158695 TI - Risk and Rationality in Adolescent Decision Making: Implications for Theory, Practice, and Public Policy. AB - Crime, smoking, drug use, alcoholism, reckless driving, and many other unhealthy patterns of behavior that play out over a lifetime often debut during adolescence. Avoiding risks or buying time can set a different lifetime pattern. Changing unhealthy behaviors in adolescence would have a broad impact on society, reducing the burdens of disease, injury, human suffering, and associated economic costs. Any program designed to prevent or change such risky behaviors should be founded on a clear idea of what is normative (what behaviors, ideally, should the program foster?), descriptive (how are adolescents making decisions in the absence of the program?), and prescriptive (which practices can realistically move adolescent decisions closer to the normative ideal?). Normatively, decision processes should be evaluated for coherence (is the thinking process nonsensical, illogical, or self-contradictory?) and correspondence (are the outcomes of the decisions positive?). Behaviors that promote positive physical and mental health outcomes in modern society can be at odds with those selected for by evolution (e.g., early procreation). Healthy behaviors may also conflict with a decision maker's goals. Adolescents' goals are more likely to maximize immediate pleasure, and strict decision analysis implies that many kinds of unhealthy behavior, such as drinking and drug use, could be deemed rational. However, based on data showing developmental changes in goals, it is important for policy to promote positive long-term outcomes rather than adolescents' short-term goals. Developmental data also suggest that greater risk aversion is generally adaptive, and that decision processes that support this aversion are more advanced than those that support risk taking. A key question is whether adolescents are developmentally competent to make decisions about risks. In principle, barring temptations with high rewards and individual differences that reduce self-control (i.e., under ideal conditions), adolescents are capable of rational decision making to achieve their goals. In practice, much depends on the particular situation in which a decision is made. In the heat of passion, in the presence of peers, on the spur of the moment, in unfamiliar situations, when trading off risks and benefits favors bad long-term outcomes, and when behavioral inhibition is required for good outcomes, adolescents are likely to reason more poorly than adults do. Brain maturation in adolescence is incomplete. Impulsivity, sensation seeking, thrill seeking, depression, and other individual differences also contribute to risk taking that resists standard risk-reduction interventions, although some conditions such as depression can be effectively treated with other approaches. Major explanatory models of risky decision making can be roughly divided into (a) those, including health-belief models and the theory of planned behavior, that adhere to a "rational" behavioral decision-making framework that stresses deliberate, quantitative trading off of risks and benefits; and (b) those that emphasize nondeliberative reaction to the perceived gists or prototypes in the immediate decision environment. (A gist is a fuzzy mental representation of the general meaning of information or experience; a prototype is a mental representation of a standard or typical example of a category.) Although perceived risks and especially benefits predict behavioral intentions and risk-taking behavior, behavioral willingness is an even better predictor of susceptibility to risk taking-and has unique explanatory power-because adolescents are willing to do riskier things than they either intend or expect to do. Dual-process models, such as the prototype/willingness model and fuzzy-trace theory, identify two divergent paths to risk taking: a reasoned and a reactive route. Such models explain apparent contradictions in the literature, including different causes of risk taking for different individuals. Interventions to reduce risk taking must take into account the different causes of such behavior if they are to be effective. Longitudinal and experimental research are needed to disentangle opposing causal processes-particularly, those that produce positive versus negative relations between risk perceptions and behaviors. Counterintuitive findings that must be accommodated by any adequate theory of risk taking include the following: (a) Despite conventional wisdom, adolescents do not perceive themselves to be invulnerable, and perceived vulnerability declines with increasing age; (b) although the object of many interventions is to enhance the accuracy of risk perceptions, adolescents typically overestimate important risks, such as HIV and lung cancer; (c) despite increasing competence in reasoning, some biases in judgment and decision making grow with age, producing more "irrational" violations of coherence among adults than among adolescents and younger children. The latter occurs because of a known developmental increase in gist processing with age. One implication of these findings is that traditional interventions stressing accurate risk perceptions are apt to be ineffective or backfire because young people already feel vulnerable and overestimate their risk. In addition, research shows that experience is not a good teacher for children and younger adolescents, because they tend to learn little from negative outcomes (favoring the use of effective deterrents, such as monitoring and supervision), although learning from experience improves considerably with age. Experience in the absence of negative consequences may increase feelings of invulnerability and thus explain the decrease in risk perceptions from early to late adolescence, as exploration increases. Finally, novel interventions that discourage deliberate weighing of risks and benefits by adolescents may ultimately prove more effective and enduring. Mature adults apparently resist taking risks not out of any conscious deliberation or choice, but because they intuitively grasp the gists of risky situations, retrieve appropriate risk-avoidant values, and never proceed down the slippery slope of actually contemplating tradeoffs between risks and benefits. PMID- 26158696 TI - Rationality and the Adolescent Mind. PMID- 26158697 TI - RNA Virus Reassortment: An Evolutionary Mechanism for Host Jumps and Immune Evasion. PMID- 26158698 TI - A demonstration project implementing extended-release naltrexone in Los Angeles County. AB - BACKGROUND: Extended-released naltrexone (XR-NTX) is a Food and Drug Administration (FDA)-approved medication associated with higher rates of abstinence, reduced cravings, and delayed relapse to use. However, there is a dearth of literature on real-world implementation of XR-NTX. The Los Angeles County Department of Public Health, in collaboration with UCLA Integrated Substance Abuse Programs, developed a demonstration project to increase access to XR-NTX. This article describes that project, along with data on the expansion of XR-NTX service delivery and patient uptake. METHODS: A secondary descriptive data analysis of demographics, substance use history, current substance use behaviors, health-related variables, and dosing records was conducted on 609 patients who received XR-NTX from Los Angeles County substance use disorder (SUD) treatment facilities from April 2010 through July 2013. A geographic information system approach mapped the distribution of XR-NTX-referring agencies across Los Angeles County. RESULTS: Of the 609 records analyzed, a majority of patients (64%) obtained more than 1 dose of XR-NTX. Most XR-NTX patients reported alcohol use disorder (71.9%; n = 438). Compared with the general Los Angeles County substance use disorder patients, XR-NTX recipients reported more severe substance use histories. Finally, XR-NTX was accessed by providers in 6 of the 8 Service Planning Areas of Los Angeles County. CONCLUSIONS: These findings reflect a higher XR-NTX cessation rate and a lower average number of doses, in contrast to similar demonstration projects in community settings with patients on parole or probation. However, this study shows that it is feasible to engage treatment providers in the use XR-NTX among their patients with alcohol or opioid use disorders. Several implications for future research and implementation are discussed. PMID- 26158699 TI - Telmisartan reduces atrial arrhythmia susceptibility through the regulation of RAS-ERK and PI3K-Akt-eNOS pathways in spontaneously hypertensive rats. AB - Telmisartan is an angiotensin II receptor blocker that displays unique PPAR-gamma modulating activity. PPAR-gamma agonists have been shown to decrease susceptibility to atrial fibrillation through their antioxidant and antiapoptotic effects. The aim of this study was to determine whether telmisartan would have a greater effect on susceptibility to atrial arrhythmia in a hypertensive rat model than valsartan, which is a traditional angiotensin II receptor blocker. In this study, spontaneously hypertensive rats were treated with 10 mg.(kg body mass)( 1).d(-1) telmisartan (TEL group), 10 mg.(kg body mass)(-1).d(-1) valsartan (VAL group), or vehicle (saline; SHR group) for 4 weeks. Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. After 4 weeks of treatment, we performed echocardiographic assessment, electrophysiological analysis, histological evaluation, and Western blot analysis. Telmisartan decreased systolic blood pressure to a similar extent as valsartan. Relative to the WKY controls, atrial arrhythmia susceptibility was significantly increased in the SHR group, and was significantly decreased by both telmisartan and valsartan, albeit to a greater extent with telmisartan. Arrhythmogenic atrial remodeling, including enlargement of the left atrium, myocyte hypertrophy, interstitial fibrosis, and myocyte apoptosis, was observed in the SHR group, and was accompanied by activated RAS-ERK signaling and suppressed PI3K-Akt-eNOS signaling. The results suggest that telmisartan reduced susceptibility to atrial arrhythmia to a greater extent than valsartan, ameliorated atrial remodeling, and reversed imbalances in the RAS-ERK and PI3K-Akt-eNOS pathways. PMID- 26158700 TI - A New Insight into Growth Mechanism and Kinetics of Mesoporous Silica Nanoparticles by in Situ Small Angle X-ray Scattering. AB - The growth mechanism and kinetics of mesoporous silica nanoparticles (MSNs) were investigated for the first time by using a synchrotron time-resolved small-angle X-ray scattering (SAXS) analysis. The synchrotron SAXS offers unsurpassed time resolution and the ability to detect structural changes of nanometer sized objects, which are beneficial for the understanding of the growth mechanism of small MSNs (~20 nm). The Porod invariant was used to quantify the conversion of tetraethyl orthosilicate (TEOS) in silica during MSN formation, and the growth kinetics were investigated at different solution pH and temperature through calculating the scattering invariant as a function of reaction time. The growth of MSNs was found to be accelerated at high temperature and high pH, resulting in a higher rate of silica formation. Modeling SAXS data of micelles, where a well defined electrostatic interaction is assumed, determines the size and shape of hexadecyltrimethylammonium bromide (CTAB) micelles before and after the addition of TEOS. The results suggested that the micelle size increases and the micelle shape changes from ellipsoid to spherical, which might be attributed to the solubilization of TEOS in the hydrophobic core of CTAB micelles. A new "swelling shrinking" mechanism is proposed. The mechanism provides new insights into understanding MSN growth for the formation of functional mesoporous materials exhibiting controlled morphologies. The SAXS analyses were correlated to the structure of CTAB micelles and chemical reaction of TEOS. This study has provided critical information to an understanding of the growth kinetics and mechanism of MSNs. PMID- 26158701 TI - Data-Driven Method to Estimate Nonlinear Chemical Equivalence. AB - There is great need to express the impacts of chemicals found in the environment in terms of effects from alternative chemicals of interest. Methods currently employed in fields such as life-cycle assessment, risk assessment, mixtures toxicology, and pharmacology rely mostly on heuristic arguments to justify the use of linear relationships in the construction of "equivalency factors," which aim to model these concentration-concentration correlations. However, the use of linear models, even at low concentrations, oversimplifies the nonlinear nature of the concentration-response curve, therefore introducing error into calculations involving these factors. We address this problem by reporting a method to determine a concentration-concentration relationship between two chemicals based on the full extent of experimentally derived concentration-response curves. Although this method can be easily generalized, we develop and illustrate it from the perspective of toxicology, in which we provide equations relating the sigmoid and non-monotone, or "biphasic," responses typical of the field. The resulting concentration-concentration relationships are manifestly nonlinear for nearly any chemical level, even at the very low concentrations common to environmental measurements. We demonstrate the method using real-world examples of toxicological data which may exhibit sigmoid and biphasic mortality curves. Finally, we use our models to calculate equivalency factors, and show that traditional results are recovered only when the concentration-response curves are "parallel," which has been noted before, but we make formal here by providing mathematical conditions on the validity of this approach. PMID- 26158709 TI - PAND: A Distribution to Identify Functional Linkage from Networks with Preferential Attachment Property. AB - Technology advances have immensely accelerated large-scale mapping of biological networks, which necessitates the development of accurate and powerful network based algorithms to make functional inferences. A prevailing approach is to leverage functions of neighboring nodes to predict unknown molecular function. However, existing neighbor-based algorithms have ignored the scale-free property hidden in many biological networks. By assuming that neighbor sharing is constrained by the preferential attachment property, we developed a Preferential Attachment based common Neighbor Distribution (PAND) to calculate the probability of the neighbor-sharing event between any two nodes in scale-free networks, which nearly perfectly matched the observed probability in simulations. By applying PAND to a human protein-protein interaction (PPI) network, we showed that smaller probabilities represented closer functional linkages between proteins. With the PAND-derive linkages, we were able to build new networks where the links are more functionally reliable than those of the human PPI network. We then applied simple annotation schemes to a PAND-derived network to make reliable functional predictions for proteins. We also developed an R package called PANDA (PAND derived functional Associations) to implement the methods proposed in this study. In conclusion, PAND is a useful distribution to calculate the probability of the neighbor-sharing events in scale-free networks. With PAND, we are able to extract reliable functional linkages from real biological networks and builds new networks that are better bases for further functional inference. PMID- 26158711 TI - [Depression in Old Age--Challenge of an Ageing Society]. AB - Besides dementia, depressive disorders belong to the most common mental disorders in the elderly. Along with the demographic change and the associated increasing proportion of older people aged 65 and more they become a central and urgent challenge. Depressive disorders in old age are treatable, although they involve special features when compared to younger adults. Guidelines are considered to be of great importance in the optimization of treatments. But how will the treatment of depressive disorders in the elderly displayed in the current guidelines? A systematic search for treatment recommendations in current evidence- and consensus-based guidelines regarding psychotherapeutic and psychosocial treatment approaches indicates that this highly relevant patient group has been strongly neglected so far. PMID- 26158710 TI - Deamidation of Human gammaS-Crystallin Increases Attractive Protein Interactions: Implications for Cataract. AB - Deamidation of proteins is one of the most prevalent post-translational modifications found upon aging, and in age-onset diseases. Specific asparagine and glutamine residues are often selectively deamidated during this process. In the human lens, deamidation has been shown to occur in many crystallins, but it is not clear how these deamidated proteins lead to lens opacity or cataract. Here we have modeled in vitro the effect of deamidation of specific asparagine and glutamine residues in human recombinant gammaS-crystallin (HGS) on the solution properties of the protein. The residues selected for deamidation in vitro are those that are found to be deamidated in aged and cataractous lenses in vivo. Two derivatives were prepared, one with Asn76 and Asn143 deamidated (2N-HGS) and the other with two additional Gln residues (92 and 120) deamidated (2N2Q-HGS). Isoelectric focusing measurements showed the expected lowering of the pI from 6.9 in HGS to ~6.5 in 2N-HGS and to ~6.1 in 2N2Q-HGS. However, spectroscopic studies showed no significant change in the secondary and tertiary structures of the deamidated proteins relative to the wild type. The stability of 2N-HGS and 2N2Q HGS, as measured by guanidinium hydrochloride unfolding, also remained comparable to that of HGS. The main difference was the altered protein-protein interaction among the three proteins. The net repulsive interactions that are characteristic of HGS are diminished in the deamidated derivatives as evidenced by static light scattering measurements of the second virial coefficient, B2 (B2 values for HGS, 2N-HGS, and 2N2Q-HGS of 8.90 * 10(-4), 7.10 * 10(-4), and 6.65 * 10(-4) mL mol g( 2), respectively). Further substantiation is provided by estimates of the excess binding energy of protein-protein interactions in the condensed phase, obtained from measurements of the PEG-induced liquid-liquid phase separation profiles for the three proteins. The data suggest that enhanced attractive protein-protein interactions, arising from the deamidation of HGS, promote protein aggregation, thereby leading to increased light scattering and opacity over time. PMID- 26158712 TI - [MVT - A Multiprofessional Behavioural Therapy Program for Inpatient Treatment of Depression in Old Age]. AB - OBJECTIVE: Depression in old age is common but patients are rarely treated in specialized units implementing a psychotherapeutic treatment approach. METHODS: A multiprofessional behavioral therapy program (MVT) for inpatient treatment of depressive elderlies was conceptualized, implemented and evaluated at a specialized unit of a hospital for psychiatry and psychotherapy. RESULTS: Preliminary analyses indicated that various behavioral group interventions were well accepted by patients. CONCLUSIONS: The implementation of a psychotherapeutic therapy program specifically designed for depressed elderly inpatients is feasible and could be more broadly applied to improve clinical practice for this patient group. PMID- 26158713 TI - [Depression Symptoms of Mothers and Fathers of Persons with Schizophrenia]. AB - OBJECTIVE: The purpose of the present study was to investigate if depression symptomatology of patients' parents is predicted by the symptoms of schizophrenia. METHODS: 101 mothers and 101 fathers of the same patients suffering from schizophrenia were included into this study. Parents filled in the "Beck Depression Inventory". Patients were assessed by means of the "Positive and Negative Syndrome Scale". For statistical analyses a Multidimensional Random Coefficients Multinomial Logit Model was applied. RESULTS: We found a significant positive association between negative symptoms and depression severity of fathers and mothers. Further, a significant positive association between positive symptoms and depression severity of fathers, but not of mothers was found. CONCLUSION: Our results show that depression of mothers and of fathers is associated with symptoms of schizophrenia even when controlling for potential predictors. PMID- 26158714 TI - [Trialogical Evaluation of a Gerontological Psychiatric Consulting and Liaison Service]. AB - Objective: The presented project shows the effects of a gerontological psychiatric consulting and liaison service (C&L) on nursing home residents and the care team. Methods: The implementation of the C&L was evaluated using a quasi experimental design in longitudinal section of residents', nursing, medical and family perspective using quantitative and qualitative methods. Results/Conclusion: The results provide evidence for the positive effects of C&L especially in relation to the "common action" within the care team. PMID- 26158715 TI - [Mental Health Professionals' Perspectives Towards Desire for Children and Family Planning Among Psychiatric Patients - Results of a Qualitative Study]. AB - Study aims: Analysis of mental health professionals' attitudes to reproductive issues among psychiatric patients. Method: 31 problem-centered semi-structured interviews with psychiatric professionals were conducted and analyzed by content analysis methods. Results: Outside of psychotherapeutic treatment the desire for children is generally assessed as less important in the context of mental health care, it is often limited to effective birth control with regard to drug treatment. Mental health professionals perceive moral concerns, lack of expertise among professionals and individual doubts as barriers when dealing with reproductive issues. Discussion: In order to meet psychiatric patients' reproductive needs, perceptions of barriers among mental health professionals in dealing with reproductive issues should be reflected and discussed. Recommendations could support professionals and help ensure adequate support for psychiatric patients. PMID- 26158716 TI - [Psychiatric Emergencies in the Emergency Room of the Ulm University Hospital in 2000 and 2010]. AB - Objective: Despite of the importance of psychiatric emergencies (PE) requiring treatment at an emergency room (ER) little is known about their frequency and current trends in terms of quantity and quality. Methods: A retrospective analysis of all PE treated at the ER of the University Hospital Ulm (Germany) in 2000 and 2010. Results: 6 % (2000) or 5 % (2010) of the ER cases were PE. Despite an increase from 369 to 430 cases (+ 16,5 %) their share decreased because of an even stronger increase of other emergencies (+ 33 %). The most frequent PE in 2000 was alcohol intoxication (37,7 %), while it was intoxication with prescribed and/or illicit drugs in 2010 (47,9 %). Patients with alcohol intoxications were significantly younger in 2010 as compared with 2000. Suicide attempts were seen in every fourth PE. They were significantly more frequent in 2010. PEs were generally more frequent in the evening and over the night. Conclusion: This study provides first insight into current trends in PE treated at the ER in Germany. Our data provide an empirical starting point for optimizing clinical care, although the study is limited by its retrospective and mono-centric design. PMID- 26158717 TI - [Barriers and Opportunities for Optimized Treatment of Late Life Depression]. AB - Objective: To identify barriers and opportunities of an optimized treatment of depression in late life in Germany. Methods: Qualitative analysis of 12 expert interviews. Results: Experts recognized much room for improvement regarding late life depression care. A number of barriers were identified on the part of individuals affected, caring relatives and physicians and other therapists, as well as at the structural level. Lack of knowledge as well as a number of structural barriers result in diagnostic deficits and limited or inadequate treatment. The potential for improvement is explored. Conclusions: Parallel initiatives at different levels of care are suggested to optimize the treatment of depressed elderly people in Germany. PMID- 26158718 TI - [Rejection of Care (Nursing or Medication) in Elder Psychiatric Patients]. AB - OBJECTIVE: Rejecting nursing or medication is an increasing challenge for professional care in elderly people. METHODS: This explorative study was part of the Gerontopsychiatry study Berlin (Gepsy-B), an investigation of the data of all older inpatients (>= 65 years) admitted to a psychiatric hospital within 3 years (1266 admissions). RESULTS: 150 cases (11.8 %) rejected care. 94 (7.4 %) refused nursing and 89 (7.0 %) medication intake. 79.3 % of them suffered from organic brain diseases, particularly from delirium superimposed on dementia (ICD-10 F05.1). Nursing was more often rejected by older and more severely cognitive impaired patients, while refusal of medication was associated with delusions. CONCLUSIONS: Resisting nursing and refusing medication are 2 separate behavioral syndromes that may also occur together. PMID- 26158719 TI - [Non-Pharmacological Interventions for the Prevention of Weight Gain in Schizophrenic Patients Treated with Antipsychotic Medication]. AB - OBJECTIVE: To evaluate the effect of non-pharmacological interventions to prevent anti-psychotic medication induced weight gain in patients with a first episode of schizophrenia. METHODS: We searched electronic databases Medline, Embase and PsychINFO and reference lists of articles. Controlled trials evaluating the beneficial effects of non-pharmacological interventions to prevent weight gain were eligible for inclusion. Two authors independently assessed the risk of bias of the studies and extracted data. RESULTS: 9 studies met the inclusion criteria. Evaluation of studies was carried out separately according to the different interventions. Six studies examined the effect of behavioral interventions. Two meta-analysis were conducted and found small effects on weight management in favor of the behavioral intervention. Three studies reported the effect of nutritional counselling yielding contradictory results . CONCLUSIONS: There is currently no clear evidence which intervention is the best to prevent antipsychotic-induced weight gain in patients with first episode of schizophrenia. Further trials of high methodological quality are necessary. PMID- 26158720 TI - Tunneling Desorption of Single Hydrogen on the Surface of Titanium Dioxide. AB - We investigated the reaction mechanism of the desorption of single hydrogen from a titanium dioxide surface excited by the tip of a scanning tunneling microscope (STM). Analysis of the desorption yield, in combination with theoretical calculations, indicates the crucial role played by the applied electric field. Instead of facilitating desorption by reducing the barrier height, the applied electric field causes a reduction in the barrier width, which, when coupled with the electron excitation induced by the STM tip, leads to the tunneling desorption of the hydrogen. A significant reduction in the desorption yield was observed when deuterium was used instead of hydrogen, providing further support for the tunneling-desorption mechanism. PMID- 26158722 TI - High-performance PdNi alloy structured in situ on monolithic metal foam for coalbed methane deoxygenation via catalytic combustion. AB - A monolithic Ni-foam@PdNi(alloy) catalyst is tailored for coalbed methane deoxygenation via galvanically depositing Pd nanoparticles on a Ni-foam surface followed by in situ activation. Experimental and theoretical studies unanimously reveal that the in situ formed PdNi alloy contributes to high activity/selectivity, good stability and oscillation elimination. PMID- 26158723 TI - Biodiversity on the Rocks: Macrofauna Inhabiting Authigenic Carbonate at Costa Rica Methane Seeps. AB - Carbonate communities: The activity of anaerobic methane oxidizing microbes facilitates precipitation of vast quantities of authigenic carbonate at methane seeps. Here we demonstrate the significant role of carbonate rocks in promoting diversity by providing unique habitat and food resources for macrofaunal assemblages at seeps on the Costa Rica margin (400-1850 m). The attendant fauna is surprisingly similar to that in rocky intertidal shores, with numerous grazing gastropods (limpets and snails) as dominant taxa. However, the community feeds upon seep-associated microbes. Macrofaunal density, composition, and diversity on carbonates vary as a function of seepage activity, biogenic habitat and location. The macrofaunal community of carbonates at non-seeping (inactive) sites is strongly related to the hydrography (depth, temperature, O2) of overlying water, whereas the fauna at sites of active seepage is not. Densities are highest on active rocks from tubeworm bushes and mussel beds, particularly at the Mound 12 location (1000 m). Species diversity is higher on rocks exposed to active seepage, with multiple species of gastropods and polychaetes dominant, while crustaceans, cnidarians, and ophiuroids were better represented on rocks at inactive sites. Macro-infauna (larger than 0.3 mm) from tube cores taken in nearby seep sediments at comparable depths exhibited densities similar to those on carbonate rocks, but had lower diversity and different taxonomic composition. Seep sediments had higher densities of ampharetid, dorvilleid, hesionid, cirratulid and lacydoniid polychaetes, whereas carbonates had more gastropods, as well as syllid, chrysopetalid and polynoid polychaetes. Stable isotope signatures and metrics: The stable isotope signatures of carbonates were heterogeneous, as were the food sources and nutrition used by the animals. Carbonate delta13Cinorg values (mean = -26.980/00) ranged from -53.30/00 to +10.00/00, and were significantly heavier than carbonate delta13Corg (mean = -33.830/00), which ranged from -74.40/00 to -20.60/00. Invertebrates on carbonates had average delta13C (per rock) = -31.00/00 (range -18.50/00 to -46.50/00) and delta15N = 5.70/00 (range -4.50/00 to +13.40/00). Average delta13C values did not differ between active and inactive sites; carbonate fauna from both settings depend on chemosynthesis-based nutrition. Community metrics reflecting trophic diversity (SEAc, total Hull Area, ranges of delta13C and delta15N) and species packing (mean distance to centroid, nearest neighbor distance) also did not vary as a function of seepage activity or site. However, distinct isotopic signatures were observed among related, co-occurring species of gastropods and polychaetes, reflecting intense microbial resource partitioning. Overall, the substrate and nutritional heterogeneity introduced by authigenic seep carbonates act to promote diverse, uniquely adapted assemblages, even after seepage ceases. The macrofauna in these ecosystems remain largely overlooked in most surveys, but are major contributors to biodiversity of chemosynthetic ecosystems and the deep sea in general. PMID- 26158724 TI - Validity and Reliability of the Brazilian Version of the Rapid Estimate of Adult Literacy in Dentistry--BREALD-30. AB - OBJECTIVE: The aim of the present study was to translate, perform the cross cultural adaptation of the Rapid Estimate of Adult Literacy in Dentistry to Brazilian-Portuguese language and test the reliability and validity of this version. METHODS: After translation and cross-cultural adaptation, interviews were conducted with 258 parents/caregivers of children in treatment at the pediatric dentistry clinics and health units in Curitiba, Brazil. To test the instrument's validity, the scores of Brazilian Rapid Estimate of Adult Literacy in Dentistry (BREALD-30) were compared based on occupation, monthly household income, educational attainment, general literacy, use of dental services and three dental outcomes. RESULTS: The BREALD-30 demonstrated good internal reliability. Cronbach's alpha ranged from 0.88 to 0.89 when words were deleted individually. The analysis of test-retest reliability revealed excellent reproducibility (intraclass correlation coefficient = 0.983 and Kappa coefficient ranging from moderate to nearly perfect). In the bivariate analysis, BREALD-30 scores were significantly correlated with the level of general literacy (rs = 0.593) and income (rs = 0.327) and significantly associated with occupation, educational attainment, use of dental services, self-rated oral health and the respondent's perception regarding his/her child's oral health. However, only the association between the BREALD-30 score and the respondent's perception regarding his/her child's oral health remained significant in the multivariate analysis. CONCLUSION: The BREALD-30 demonstrated satisfactory psychometric properties and is therefore applicable to adults in Brazil. PMID- 26158725 TI - The C-Reactive Protein/Albumin Ratio as an Independent Predictor of Mortality in Patients with Severe Sepsis or Septic Shock Treated with Early Goal-Directed Therapy. AB - BACKGROUND: Sepsis, including severe sepsis and septic shock, is a major cause of morbidity and mortality. Albumin and C-reactive protein (CRP) are considered as good diagnostic markers for sepsis. Thus, initial CRP and albumin levels were combined to ascertain their value as an independent predictor of 180-day mortality in patients with severe sepsis and septic shock. MATERIALS AND METHODS: We conducted a retrospective cohort study involving 670 patients (>18 years old) who were admitted to the emergency department and who had received a standardized resuscitation algorithm (early goal-directed therapy) for severe sepsis and septic shock, from November 2007 to February 2013, at a tertiary hospital in Seoul, Korea. The outcome measured was 180-day all-cause mortality. A multivariate Cox proportional hazard model was used to identify the independent risk factors for mortality. A receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the CRP/albumin ratio at admission. RESULTS: The 180-day mortality was 28.35% (190/670). Based on the multivariate Cox proportional hazard analysis, age, the CRP/albumin ratio at admission (adjusted HR 1.06, 95% CI 1.03-1.10, p<0.001), lactate level at admission (adjusted HR 1.10, 95% CI 1.05-1.14, p<0.001), and the Sequential Organ Failure Assessment (SOFA) score at admission (adjusted HR 1.12, 95% CI 1.07-1.18, p<0.001) were independent predictors of 180-day mortality. The area under the curve of CRP alone and the CRP/albumin ratio at admission for 180-day mortality were 0.5620 (P<0.001) and 0.6211 (P<0.001), respectively. CONCLUSION: The CRP/albumin ratio was an independent predictor of mortality in patients with severe sepsis or septic shock. PMID- 26158726 TI - Context-Specific Metabolic Model Extraction Based on Regularized Least Squares Optimization. AB - Genome-scale metabolic models have proven highly valuable in investigating cell physiology. Recent advances include the development of methods to extract context specific models capable of describing metabolism under more specific scenarios (e.g., cell types). Yet, none of the existing computational approaches allows for a fully automated model extraction and determination of a flux distribution independent of user-defined parameters. Here we present RegrEx, a fully automated approach that relies solely on context-specific data and l1-norm regularization to extract a context-specific model and to provide a flux distribution that maximizes its correlation to data. Moreover, the publically available implementation of RegrEx was used to extract 11 context-specific human models using publicly available RNAseq expression profiles, Recon1 and also Recon2, the most recent human metabolic model. The comparison of the performance of RegrEx and its contending alternatives demonstrates that the proposed method extracts models for which both the structure, i.e., reactions included, and the flux distributions are in concordance with the employed data. These findings are supported by validation and comparison of method performance on additional data not used in context-specific model extraction. Therefore, our study sets the ground for applications of other regularization techniques in large-scale metabolic modeling. PMID- 26158727 TI - The Alternative Sigma Factor SigX Controls Bacteriocin Synthesis and Competence, the Two Quorum Sensing Regulated Traits in Streptococcus mutans. AB - Two small quorum sensing (QS) peptides regulate competence in S. mutans in a cell density dependent manner: XIP (sigX inducing peptide) and CSP (competence stimulating peptide). Depending on the environmental conditions isogenic S. mutans cells can split into a competent and non-competent subpopulation. The origin of this population heterogeneity has not been experimentally determined and it is unknown how the two QS systems are connected. We developed a toolbox of single and dual fluorescent reporter strains and systematically knocked out key genes of the competence signaling cascade in the reporter strain backgrounds. By following signal propagation on the single cell level we discovered that the master regulator of competence, the alternative sigma factor SigX, directly controls expression of the response regulator for bacteriocin synthesis ComE. Consequently, a SigX binding motif (cin-box) was identified in the promoter region of comE. Overexpressing the genetic components involved in competence development demonstrated that ComRS represents the origin of bimodality and determines the modality of the downstream regulators SigX and ComE. Moreover these analysis showed that there is no direct regulatory link between the two QS signaling cascades. Competence is induced through a hierarchical XIP signaling cascade, which has no regulatory input from the CSP cascade. CSP exclusively regulates bacteriocin synthesis. We suggest renaming it mutacin inducing peptide (MIP). Finally, using phosphomimetic comE mutants we show that unimodal bacteriocin production is controlled posttranslationally, thus solving the puzzling observation that in complex media competence is observed in a subpopulation only, while at the same time all cells produce bacteriocins. The control of both bacteriocin synthesis and competence through the alternative sigma-factor SigX suggests that S. mutans increases its genetic repertoire via QS controlled predation on neighboring species in its natural habitat. PMID- 26158729 TI - Treatment of Prominent Ears and Otoplasty: A Contemporary Review. AB - Prominent ears affect approximately 5% of the population and can have a significant psychological impact on patients. A wide variety of otoplasty techniques have been described, all sharing the goal of re-creating the normal appearance of the ear and achieving symmetry between the 2 sides. Recent trends in otoplasty techniques have consistently moved toward less invasive options, ranging from nonsurgical newborn ear molding to cartilage-sparing surgical techniques and even incisionless, office-based procedures. Herein, we review anatomy of the external ear, patient evaluation, the evolution of nonsurgical and surgical otoplasty techniques, otoplasty outcomes, and future trends for treatment of prominent ears. PMID- 26158728 TI - Heterogeneous Network Edge Prediction: A Data Integration Approach to Prioritize Disease-Associated Genes. AB - The first decade of Genome Wide Association Studies (GWAS) has uncovered a wealth of disease-associated variants. Two important derivations will be the translation of this information into a multiscale understanding of pathogenic variants and leveraging existing data to increase the power of existing and future studies through prioritization. We explore edge prediction on heterogeneous networks- graphs with multiple node and edge types--for accomplishing both tasks. First we constructed a network with 18 node types--genes, diseases, tissues, pathophysiologies, and 14 MSigDB (molecular signatures database) collections--and 19 edge types from high-throughput publicly-available resources. From this network composed of 40,343 nodes and 1,608,168 edges, we extracted features that describe the topology between specific genes and diseases. Next, we trained a model from GWAS associations and predicted the probability of association between each protein-coding gene and each of 29 well-studied complex diseases. The model, which achieved 132-fold enrichment in precision at 10% recall, outperformed any individual domain, highlighting the benefit of integrative approaches. We identified pleiotropy, transcriptional signatures of perturbations, pathways, and protein interactions as influential mechanisms explaining pathogenesis. Our method successfully predicted the results (with AUROC = 0.79) from a withheld multiple sclerosis (MS) GWAS despite starting with only 13 previously associated genes. Finally, we combined our network predictions with statistical evidence of association to propose four novel MS genes, three of which (JAK2, REL, RUNX3) validated on the masked GWAS. Furthermore, our predictions provide biological support highlighting REL as the causal gene within its gene-rich locus. Users can browse all predictions online (http://het.io). Heterogeneous network edge prediction effectively prioritized genetic associations and provides a powerful new approach for data integration across multiple domains. PMID- 26158730 TI - Evaluation of Neoadjuvant Radiochemotherapy Response (RCT) in Squamous Esophageal Cancer (ESC) and Implications in Therapeutic Conduct. AB - The multidisciplinary approach in ESC emerged as a result of efforts to maximize the treatment outcome of this disease.Surgical approach as the only therapeutic option is not always followed by a good distance survival. A concomitant neoadjuvant radiochemotherapy in ESC may result in a favourable outcome for responding patients, reducing the size of the tumor and the degree of lymph node damage increasing resectability and the R0 resection rate, improving prognosis. For non-responding patients or if the disease continues to progress under RCT therapy, the surgical time is delayed, adverse effects of radiochemotherapy are added and postoperative morbidity and mortality are increased. The imaging methods for the assessment of response have only limited value and metabolic response; only FDG-PET manages to come close to pathological response. Determining the response degree is very important for the establishment of the surgical conduct: planned or necessity surgery, or non-surgical palliative therapy. PMID- 26158731 TI - The Role of Collagen Metabolism in the Formation and Relapse of Incisional Hernia. AB - Despite the continuous development of synthetic prosthetic meshes and their wide use, recurrent incisional hernias still appear in 5 to 20% of cases, with a linear incidence curve over the years, suggesting a multifactorial process rather than a simple failing technical repair as the underlying cause. Recent molecular biological research provide increasing evidence of connective tissue alterations such as a defective wound healing with impaired scarring process in patients with incisional hernia. Although there are some promising results, at present, in depth understanding of the pathophysiological mechanisms and of the role that collagens play in the development and recurrence of incisional hernia is rather scarce. The aim of this systematic review is to summarize and evaluate the biochemical mechanisms involved in incisional hernia formation and recurrence, with a primary focus on collagen I to III ratio. Also, the consequences for surgical practice are discussed. PMID- 26158732 TI - Morbidity after Ultra Low Anterior Resection of the Rectum. AB - Anterior resections of the rectum, used as an alternative to amputation of the rectum, are performed more and more frequently, being presently indicated for neoplasms located ata distance of 7 to 4 cm from the anus. Complications of low and ultra low anterior resections are not at all negligible, and local neoplastic recurrence rate is significantly higher than after amputation of the rectum. However, literature data recommends low and ultra low anterior rectal resections, even if sometimes the method indications are pushed to the limit or the interventions are performed at the patient's request, in order to avoid permanent colostomy. The authors of this article aim to outline a true picture of the changes caused by anterior resections of the rectum, low and ultra low, so that, without denying the merits of these resections, the entire postoperative pathology that occurs in these patients is depicted and understood. Ultra low rectal resections, up to 3-4 cm from the anus, bring important morphological and functional changes to the act of defecation and to anal continence. These changes in colo-anal bowel movement have a much higher incidence than postoperative genitourinary disorders. Another important aspect emerging from the present study is related to the increased incidence of anastomotic disunity, stenosis and various degrees of incontinence, complications that often can only be solved by completion of rectum amputation and permanent colostomy. In addition, the functional outcomes of these ultra low resections are not always at the level expected by the patient. Also, in terms of surgical performance, the higher share of specific complications of the procedure raises questions with regard to the technique. For all these reasons the authors consider it necessary to review the lower limit to which an anterior rectal resection can descend. PMID- 26158733 TI - "Difficult" Colorectal Polyps - Therapeutic Approach. AB - INTRODUCTION: Endoscopic polypectomy is the gold standard in the treatment of colorectal polyps. The importance of polypectomy rests primarily on the fact that polyp-type lesions present a high risk of malignant degeneration, colorectal polyps being able, if left unattended therapeutically, to generate a colorectal cancer (CRC) - a lesion with a far more negative prognosis. Although preferable, endoscopic polypectomy of colorectal polyps is not always possible, multiple factors generating difficulties in performing this therapeutic measure. MATERIAL AND METHOD: We performed a retrospective study in the First Surgical Clinic of the "Prof. Dr. Alexandu Trestioreanu" Bucharest Oncology Institute, spanning a period of 3 years (2008-2011), in which time 224 patients were diagnosed by colonoscopy with colorectal polyps, of whom 222 patients benefited from endoscopic polypectomy. The aim of the study was to identify "difficult" polyps and to identify the criteria for endoscopic surgery versus classic surgery as a therapeutic indication. RESULTS: Presence of "difficult" polyps was observed in 37.56% of the patients diagnosed with colorectal polyps. In over 88% of cases endoscopic polypectomy was possible, and for the remaining patients classic surgery was the therapeutic solution opted for. CONCLUSIONS: Presence of "difficult" polyps generates inconveniences in performing endoscopic polypectomy, increasing the risk of postoperative complication occurrence, as well as the duration of the operation. If the criteria for characterizing polyps as "difficult" are relatively well-established, the choice between endoscopic and classic surgery as a therapeutic measure is left at the free will of the operating surgeon, with the exception of situations in which classic surgery is resorted to for oncological reasons. PMID- 26158734 TI - Surgical Treatment with Radiofrequencies for Outpatients with Surgical Benign Ano Perianal Diseases. AB - INTRODUCTION: Nowadays, the occurrence of surgical benign ano-perianal diseases (SBAPD) is raising. Radiofrequency (RF) represents a surgical therapeutic method using high frequency radio waves to perform incisions, excisions and tissue coagulation. The main purpose of the study is to validate the possibility to use RF within the surgical treatment for outpatients with SBAPD; at the same time, a special consideration has been given to appreciate the efficiency of RF compared with other surgical methods. MATERIAL AND METHOD: The study presents the results accumulated in 11 years (December 2003 - December 2014) in "PROCTOLINE" International Medical Center; also, we have taken into account the accomplishments on 783 outpatients, submitted to RF surgery for 10 different types of SBAPD. Various RF surgeries (cuttings, excisions, coagulations, curettages etc.) have been performed under local anesthesia. RESULTS: The necessary time was usually less than 45 minutes, while the post-operatory duration for a total healing was in the range of 7 to 45 days. The percentage of minor complications was quite a small one (8,3%). Also, we might appreciate excellent post-treatment results (maximum value of 11 years); Typically, the patients return for periodic postoperative examination at first and fourth week after surgery. CONCLUSIONS: RF represents an efficient, rapid and secure method for the treatment of SBAPD; it may be used in ambulatory, only under local anesthesia, offering to the patient a minimal post-operatory discomfort, as well as a rapid, esthetic and functional recovery of wound. By comparison with "classical surgery", the complications are rather minor ones and their percentage occurs in a lesser one. PMID- 26158735 TI - GSTM1, GSTT1 and GSTP1 Genetic Variants in Multiple Urologic Cancers. AB - INTRODUCTION: Glutathione S-transferases (GSTs) are phase 2 enzymes responsible for catalyzing the biotransformation of a wide variety of electrophilic compounds, having a crucial role in the detoxification of active metabolites of procarcinogens produced by phase 1 reactions, tying them to glutathione and promoting their excretion in the urine. OBJECTIVES: we evaluated GSTM1, GSTT1 and GSTP1 genotypes in patients diagnosed with multiple malignancies, of which at least one was found in the prostate, bladder or kidney. MATERIALS AND METHODS: GSTM1, GSTT1 and GSTP1 genotypes were genetically assessed in 34 patients with multiple urologic cancers and 23 patients with urologic cancer associated with another type of cancer. RESULTS: in the group of patients with multiple urologic cancers, GSTT1 null genotype was found in 26.4% of patients compared to 0% in controls, 82.35 % of patients and 47% of witnesses carried at least one GSTM1 or GSTT1 null genotype, and in the group with different cancers, GSTM1 null genotype was found in 52.1% of patients compared to 4.3% witnesses in the control group; GSTT1 null genotype was found in 34.7% of patients compared to 4.3% of witnesses, atleast one GSTM1 or GSTT1 null genotype was found in 73.9% of patients compared to 8.6% of controls. CONCLUSIONS: GSTT1 null genotype is a risk factor for patients with more primitive urologic malignancies (bladder, prostate and kidney); GSTM1 or GSTT1 null genotype is more frequent in patients with multiple urologic tumors; GSTM1 and GSTT1 null genotypes are risk factors in patients with different types of cancer, with at least one affecting the urinary system. PMID- 26158736 TI - Value of Endorectal MRI in Romanian Men for High Risk of Prostate Cancer: MRI Findings Compared with Saturation Biopsy. AB - PURPOSE: To evaluate the potentials of T2 weighted (T2W)MRI and diffusion weighted (DW) MRI for prostate cancer(PCa) detection, local staging and treatment planning in high-risk group. MATERIAL AND METHODS: Endorectal MRI was performed in 17 Romanian men (median age: 66 years; range: 58 75 years), prostate specific antigen (PSA) serum levels (median: 20 ng mL; range: 8.6 100 ng mL) with positive findings for PCa(median Gleason score: 8; range: 7 - 9). Imaging findings were compared to standarised 20-core transperineal saturation biopsy. The prostate was divided into 16 standart sectors(10 posterior and 6 anterior). RESULTS: Overall, prostate cancer was detected in 16 patients(94%) on DW-MRI alone and in all 17 patients (100%) on T2W-MRI alone, and on combined imaging. On T2W-MRI165 sectors out of 272 were suspicious for PCa and 124 (75%)were cancer positive. On DW-MRI 126 sectors out of 272 were suspicious for PCa and 118 (95%) were cancer positive. On the combined imaging approach 134 sectors out of 272 were suspicious for PCa and 126 (94%) were cancer positive. This resulted in diagnostic accuracies per sector of 76% for T2WMRI, 86% for DW-MRI and 89% for combined imaging. Multifocal PCa was confirmed both on MR imaging and by biopsy in 8 of the 17 men (47%) Extra capsular extension(ECE) or seminal vesicles invasion (SVI) was highly suspected in 8 (47%) respectively 7 (41%) of the 17 patients. 6 patients(35%) presented both ECE and SVI. MRI findings were taken into account for treatment planning and none of these patients underwent radical prostatectomy and instead was treated with palliative cryotherapy, radiotherapy and hormone therapy. CONCLUSIONS: Endorectal MRI is highly accurate in PCa detection in the high-risk group and seems to have an important role in local staging and treatment planning for Romanian population. PMID- 26158737 TI - Laparoscopic Mesh Sacropexy for Voluminous Rectocele. AB - The rectocele represents a protrusion of the rectum through the rectovaginal fascia, which appears as a bulge in the posterior vaginal wall. Surgical treatment includes many procedures which can be performed by four types of approaches: transvaginal, transanal, transperineal and transabdominal.Voluminous rectocele cases are rare and often represent a surgical challenge. Only two types of approaches are proved to be feasible for the treatment of a voluminous rectocele, the transvaginal and the transabdominal approaches. To resolve these cases, the authors propose laparoscopic mesh sacropexy.The procedure implies retrorectal dissection and rectovaginal dissection down to the pelvic floor, followed by a rectovaginopexy to the sacral promontory, using an y-shaped polypropylene mesh. One arm of the mesh is fixed to the anterior rectal wall using four stitches and the other arm is sutured to the posterior vaginal wall. The end of the mesh is fixed to the promontory. Thus, the anchoring of the prolapsed rectum and the posterior vaginal fornix to the sacral ligamentis achieved, the damaged rectovaginal fascia being substituted by the polypropylene mesh. The main symptom that was tracked, difficulty in defecation, was significantly improved, none of the patients needed any longer digital maneuvers to empty the rectum. The good results of the first experience make us believe that this procedure is an attractive solution to resolve these difficult cases. PMID- 26158738 TI - Cervico-mediastinal Esophageal Duplication Cyst - Case Presentation. AB - INTRODUCTION: esophageal cysts can be divided into 2 categories: simple epithelial-lined cysts and esophageal duplication, which is an embryologic duplication of a portion of the muscle and submucosa of the esophagus without epithelial duplication. CASE PRESENTATION: 48 year-old male, with no relevant history, was transferred in our department with vomiting, dysphagia, anorexia, and weight loss. The CT scan highlights a tumor mass, well defined, with maximum size of 6.5 cm, developed in the left upper mediastinum and lower left cervical region. We decided to perform surgery in order to remove the mass completely. The approach was through a cervical incision, allowing access to the upper mediastinum, as well as for the anterior cervical region. DISCUSSION: Complete surgical excision is recommended for all foregut cyst malformations. Considering the localization of the esophageal cyst in our patient, we decided cervico sternotomy will be the best approach, giving a wide exposure of the mediastinum and of the lower cervical region if necessary. The lesion was carefully dissected from the surrounding structures and completely removed. CONCLUSION: All esophageal cysts should be evaluated and, eventually, resected. Most patients with esophageal cysts eventually become symptomatic; therefore, cysts should be resected when they are diagnosed. PMID- 26158739 TI - Esotracheal Fistula in Esophageal Stenoses of Malignant Origin - Case Report. AB - BACKGROUND: Approximately 80% of acquired eso-tracheal or mediastinal fistulae are of malignant nature. The occurrence of an eso-respiratory malignant fistula is a devastating complication for both patient and doctor, and, if not treated, records a survival time of 1 to 6 weeks. MATHERIAL AND METHOD: We present a patient, aged 51, smoker,with progressive dysphagia, at first to solids, then to semi-solids and liquids, followed by manifestation of post-deglutition cough due to eso-tracheal fistula, incapability of feeding, and decline of the general condition. Surgical intervention consists of esophageal transstenotic endo prosthesing by transtumoral drilling with prosthetic montage and the occlusion of the eso-tracheal fistulous orifice. RESULTS: The post-operatory evolution is favorable, the feeding per os resumes in 8 hours after surgery, good digestive tolerance. The radiologic examination using contrast medium, performed in 48 hours after surgery, reveals a permeable esophageal endo-prosthesis, without reflux of contrast substance in the tracheobronchial tree. CONCLUSIONS: The laparo-gastroscopic montage of prosthesis through transtumoral drilling, using siliconized semi-rigid prostheses, represents the only efficient palliative treatment of malignant eso-tracheal or eso-bronchial fistula. PMID- 26158740 TI - Metastatic Merkel Cell Carcinoma (MCC) of Pancreas. AB - Merkel cell carcinoma (MCC) is a rare, agressive, neurocutaneous malignancy with a high potential to metastasize. We present a 59 year-old woman referred to general surgery department with a complaint of epigastric pain. The abdominal computed tomography (CT) performed and revealed amass of 3 cm in the head of the pancreas. The significant debate in the patient's medical history was that she had a MCC in size of 5 cm removed from the left gluteal region 7 months ago. Following preoperative preparation a pancreatic oduodenectomy with Whipple procedure was performed fort hepancreatic head mass. As the tumor showed morphologically similar properties with the patient's primary neoplasm, it was accepted as a metastatic MCC. Following the operation the patient received adjuvant chemotherapy and at a 30 months follow-up it was observed that the patient is disease free and has no complications related to the disease progression or recurrence. Although MCC is an aggresive and poor prognostic tumor, good results can be obtained with correct diagnosis and proper surgical treatment. PMID- 26158741 TI - Ileal J-Pouch Perforation: Case Report. AB - A 34-year-old male patient who had undergone total colectomy and J-pouch ileanal anastomosis subsequent to diagnosis of familial adenomatous polyposis five years previously was admitted to the emergency room with complaints of severe abdominal pain of a four-day duration. Physical examination revealed widespread tenderness throughout the abdomen, especially in the lower quadrant. Abdominal ultrasonography revealed fluid between intestinal loops and computed tomography revealed free air and fluid in the abdomen. During laparotomy to expand the ileal J-pouch to approximately 12 cm in diameter, a 2-mm perforation was detected in the blind end of the ileal J-pouch. The perforation was repaired primarily and protective ileostomy was performed. During postoperative endoscopy, neither obstruction nor stasis was observed, but pouchitis was observed in the ileal J pouch. The patient was postoperatively discharged on the 20th day and followed endoscopically. The endoscopic findings were normal in the sixth month postsurgery. PMID- 26158742 TI - Rare Tumors, Rare Association: Ovarian Strumal Carcinoid - Retroperitoneal Cystic Lymphangioma. AB - INTRODUCTION: Strumal carcinoid is a rare neoplasm of the ovary containing thyroid (struma) and carcinoid component revealed by immunohistochemistry. Case present: A 55-years-old woman with hysterectomy and right oophorectomy for uterine leiomyoma and right ovarian cyst, performed 12 years ago, was referred to the First Surgical Clinic, St. Spiridon University Hospital Iasi with pain in hypogastrium present for 2 months. Laboratory tests are normal and serum testing for tumor markers is unchanged. Ultrasound and CT finds for topography of the left ovary a well-defined 63 57 71 mm cystic mass, with a non-uniform wall thickness. Exploration laparoscopy, after adhesiolysis, identifies a cystic tumor developed in mesosigmoid which was excised and auterine tube with cystic dilatation and left ovary with intactcapsule, for which we performed left adnexectomy and extracted pieces of tumors in endobag. Evolution is simple, the patient being discharged after 3 days postoperatively. Histopathological exam and immunohistochemistry reveal edovarian strumal carcinoid and cystic lymphangioma. After one year follow up the patient is disease free. CONCLUSION: This association between an ovarian strumal carcinoid with mesosigmoidian cystic lymphangioma is unusual and rare, not cited in the literature. A laparoscopic approach for the two conditions is safe with good immediate and distant postoperative course. PMID- 26158743 TI - Giant Esophageal GIST: Diagnostic and Therapeutic Challenge - Case Report. AB - GIST are rare mesenchymal tumors of the digestive tract (less than 1% of the digestive tract neoplasia). Of these, less than 1% are found in the esophagus. Surgery is the main treatment of GIST and is supported by targeted therapy with tyrosine kinase inhibitors like imatinibmesylate. We present the case of a female patient of 51 years, admitted in our clinic for a bulky tumor in the posterior mediastinum, diagnosed after investigations performed for fatigue for the great efforts. Clinical examination was unspecific. Chest X-ray and thoraco-abdominal CT identified a widening of the mediastinum through a posterior mediastinal tumor mass, determining a deviation to the left of the thoracic esophagus without causing not abledysphagia or respiratory symptoms. It was decided surgery by thoracotomy in V right intercostal space and total excision of the tumor was performed. Histopathology examination confirmed the preoperative suspicion of esophageal GIST. Prognosis is reserved, the risk of relapse is very high given the fact that the tumor was extracted fragmented. Currently the patient is under treatment with imatinib mesylate and entered into clinical and imaging follow-up program, according to clinical guidelines. PMID- 26158744 TI - Erratum: Photogated humidity-driven motility. PMID- 26158746 TI - Probing the Evaporation Dynamics of Mixed SOA/Squalane Particles Using Size Resolved Composition and Single-Particle Measurements. AB - An analysis of the formation and evaporation of mixed-particles containing squalane (a surrogate for hydrophobic primary organic aerosol, POA) and secondary organic aerosol (SOA) is presented. In these experiments, one material (D62 squalane or SOA from alpha-pinene + O3) was prepared first to serve as surface area for condensation of the other, forming the mixed-particles. The mixed particles were then subjected to a heating-ramp from 22 to 44 degrees C. We were able to determine that (1) almost all of the SOA mass is comprised of material less volatile than D62-squalane; (2) AMS collection efficiency in these mixed particle systems can be parametrized as a function of the relative mass fraction of the components; and (3) the vast majority of D62-squalane is able to evaporate from the mixed particles, and does so on the same time scale regardless of the order of preparation. We also performed two-population mixing experiments to directly test whether D62-squalane and SOA from alpha-pinene + O3 form a single solution or two separate phases. We find that these two OA types are immiscible, which informs our inference of the morphology of the mixed-particles. If the morphology is core-shell and dictated by the order of preparation, these data indicate that squalane is able to diffuse relatively quickly through the SOA shell, implying that there are no major diffusion limitations. PMID- 26158745 TI - Growth-regulating Mycobacterium tuberculosis VapC-mt4 toxin is an isoacceptor specific tRNase. AB - Toxin-antitoxin (TA) systems are implicated in the downregulation of bacterial cell growth associated with stress survival and latent tuberculosis infection, yet the activities and intracellular targets of these TA toxins are largely uncharacterized. Here, we use a specialized RNA-seq approach to identify targets of a Mycobacterium tuberculosis VapC TA toxin, VapC-mt4 (also known as VapC4), which have eluded detection using conventional approaches. Distinct from the one other characterized VapC toxin in M. tuberculosis that cuts 23S rRNA at the sarcin-ricin loop, VapC-mt4 selectively targets three of the 45 M. tuberculosis tRNAs (tRNA(Ala2), tRNA(Ser26) and tRNA(Ser24)) for cleavage at, or adjacent to, their anticodons, resulting in the generation of tRNA halves. While tRNA cleavage is sometimes enlisted as a bacterial host defense mechanism, VapC-mt4 instead alters specific tRNAs to inhibit translation and modulate growth. This stress linked activity of VapC-mt4 mirrors basic features of eukaryotic tRNases that also generate tRNA halves and inhibit translation in response to stress. PMID- 26158748 TI - This special issue of Substance Use & Misuse explores"Big Events," Substance Use, and Its Interventions. Introduction. PMID- 26158747 TI - Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. A systematic review and meta-analysis. AB - Variability in vitamin K antagonist (VKA) dosing is partially explained by genetic polymorphisms. We performed a meta-analysis to determine whether genotype guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding (primary outcome) and improve time in therapeutic range (TTR). We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomised trials comparing genotype-guided and standard (non genotype guided) VKA dosing algorithms in adults initiating anticoagulation. Data were pooled using a random effects model. Of the 12 included studies (3,217 patients), six reported all components of the primary outcome of mortality, thromboembolic events and major bleeding (2,223 patients, 87 events). Our meta-analysis found no significant difference between groups for the primary outcome (relative risk 0.85, 95% confidence interval [CI] 0.54-1.34; heterogeneity Chi(2)=4.46, p=0.35, I(2)=10%). Based on 10 studies (2,767 patients), TTR was significantly higher in the genotype-guided group (mean difference (MD) 4.31%; 95% CI 0.35, 8.26; heterogeneity Chi(2)=43.31, p<0.001, I(2)=79%). Pre-specified exploratory analyses demonstrated that TTR was significantly higher when genotype-guided dosing was compared with fixed VKA dosing (6 trials, 997 patients: MD 8.41%; 95% CI 3.50,13.31; heterogeneity Chi(2)=15.18, p=0.01, I(2)=67%) but not when compared with clinical algorithm-guided dosing (4 trials, 1,770 patients: MD 0.29%; 95% CI -2.48,1.90; heterogeneity Chi(2)=1.53, p=0.68, I(2)=0%; p for interaction=0.002). In conclusion, genotype-guided compared with standard VKA dosing algorithms were not found to decrease a composite of death, thromboembolism and major bleeding, but did result in improved TTR. An improvement in TTR was observed in comparison with fixed VKA dosing algorithms, but not with clinical algorithms. PMID- 26158749 TI - Historical Trauma, Substance Use, and Indigenous Peoples: Seven Generations of Harm From a "Big Event". AB - Indigenous peoples the world over have and continue to experience the devastating effects of colonialism including loss of life, land, language, culture, and identity. Indigenous peoples suffer disproportionately across many health risk factors including an increased risk of substance use. We use the term "Big Event" to describe the historical trauma attributed to colonial policies as a potential pathway to explain the disparity in rates of substance use among many Indigenous populations. We present "Big Solutions" that have the potential to buffer the negative effects of the Big Event, including: (1) decolonizing strategies, (2) identity development, and (3) culturally adapted interventions. Study limitations are noted and future needed research is suggested. PMID- 26158750 TI - On the Cost of Big Events: Are Weather-Related Disasters as Bad as Economic Recessions for Health Disparities Related to Drug Use? AB - This commentary reviews two manuscripts about big event empirical data exploring concepts and pathways of drug use and health-related events. Using basic concepts and tools, it proposes a focused framework in order to help comprehension of the multifactorial and multilevel components between macrosocial determinants of health, contextual pathways of drug use and drug-use harm and individual levels in the episode of a big event occurrence. The text also discusses implications of preexisting conditions that may be contributing factors for socially and economically segregated subsets of the population, groups possibly "at risk of risks," meaning unequally exposed to risks that generate exposure to other risks, amplifying preexistent inequities. PMID- 26158751 TI - Some Musings About Big Events and the Past and Future of Drug Use and of HIV and Other Epidemics. AB - The term "Big Events" began as a way to help understand how wars, transitions and other crises shape long-term HIV epidemiology in affected areas. It directs attention to the roles of ordinary people in shaping these outcomes. Big Events themselves can take years, as in long-term armed struggles like those in Colombia and also long-term political and economic changes like the turn over the last 15 years of many Latin American countries away from neoliberalism and towards attempts to build solidarity economies of some form. The effects of Big Events on HIV epidemics, at least, may run in phases: In the short term, by creating vulnerability to epidemic outbreaks among existing Key Populations like people who inject drugs (PWID) or men who have sex with men (MSM); then, in their non PWID (or non-MSM) risk networks; and perhaps, several years later, among youth who became involved in high-risk sexual or drug use networks and behaviors due to the social impacts of the Big Event. Issues of time loom large in other articles in this Special Issue as well. Some articles and commentaries in this issue point to another important phenomenon that should be studied more: The positive contributions that people who use drugs and other members of the population make towards helping other people in their communities during and after Big Events. Finally, this Commentary calls for more thought and research about an impending very Big Event, global climate change, and how it may exacerbate HIV, hepatitis C and other epidemics among people who use drugs and other members of their networks and communities. PMID- 26158753 TI - Minireview: Deciphering the Cellular Functions of PELP1. PMID- 26158754 TI - Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery. AB - Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pH-sensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 ug/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine. PMID- 26158756 TI - Discovery of Novel DNA Gyrase Inhibiting Spiropyrimidinetriones: Benzisoxazole Fusion with N-Linked Oxazolidinone Substituents Leading to a Clinical Candidate (ETX0914). AB - A novel class of bacterial type-II topoisomerase inhibitor displaying a spiropyrimidinetrione architecture fused to a benzisoxazole scaffold shows potent activity against Gram-positive and fastidious Gram-negative bacteria. Here, we describe a series of N-linked oxazolidinone substituents on the benzisoxazole that improve upon the antibacterial activity of initially described compounds of the class, show favorable PK properties, and demonstrate efficacy in an in vivo Staphylococcus aureus infection model. Inhibition of the topoisomerases DNA gyrase and topoisomerase IV from both Gram-positive and a Gram-negative organisms was demonstrated. Compounds showed a clean in vitro toxicity profile, including no genotoxicity and no bone marrow toxicity at the highest evaluated concentrations or other issues that have been problematic for some fluoroquinolones. Compound 1u was identified for advancement into human clinical trials for treatment of uncomplicated gonorrhea based on a variety of beneficial attributes including the potent activity and the favorable safety profile. PMID- 26158755 TI - Looking ahead: Anticipatory cueing of attention to objects others will look at. AB - Seeing a face gaze at an object elicits rapid attention shifts toward the same object. We tested whether gaze cueing is predictive: do people shift their attention toward objects others are merely expected to look at? Participants categorized objects while a face either looked at this object, at another object, or straight ahead. Unbeknownst to participants, one face would only look at drinks and the other at foods. We tested whether attention was drawn toward objects "favored" by a face even when currently looking straight ahead. Indeed, while gaze expectations initially had a disruptive effect, participants did shift attention to the faces' favored objects once learning had been established, as long as emotional expressions had indicated personal relevance of the object to the individual. These data support predictive models of social perception, which assume that predictions can drive perception and action, as if these stimuli were directly perceived. PMID- 26158757 TI - The difference between in bed and out of bed activity as a behavioral marker of cancer patients: A comparative actigraphic study. AB - The current study was conducted to provide normative data on actigraphic dichotomy index (I < O) (the percentage of in bed activity counts that are less than the median of out of bed counts) in healthy population and to assess whether the I < O could be an effective index in discriminating the circadian motor activity of cancer patients from healthy controls. In this retrospective study, we recovered 408 actigraphic records from two databases: healthy controls (n = 182; 79 males; mean age 38.7 +/- 12.6) and patients with metastatic colorectal cancer (n = 226; 149 males; mean age 58.4 +/- 11.4). Beside the usual actigraphic sleep parameters (time in bed, sleep onset latency, total sleep time, wake after sleep onset, sleep efficiency, number of awakenings, and mean motor activity), we also computed the dichotomy index and number of actigraphic wake parameters, namely, diurnal motor activity, diurnal total sleep time, number of sleep episodes, and the mean duration of the longest diurnal sleep episode. Using the Youden index, we calculated the cut off value that performed the best for I < O and actigraphic wake parameters. Finally, we created Receiver Operator Characteristic curves to test the efficacy of each actigraphic parameter to discriminate cancer patient from healthy controls. Mean I < O was 99.5% (SD, 0.48%) in the healthy group, as compared to 96.6% (SD, 3.6%) in the cancer group (p < 0.0001). Important age-related effects appeared unlikely after performing both the main analysis with age as a covariate, and a subset analysis in 104 subjects matched for age and sex. In the main analysis, all actigraphic parameters, except total sleep time, significantly differentiated the two groups of participants. However, the I < O was the one that clearly performed best. Here, we provide the first large dataset on I < O in healthy subjects, we confirm the relevance of this circadian index for discriminating advanced stage colorectal cancer patients from healthy subjects, and we lay the grounds for further investigations of this circadian index in patients with other chronic diseases. PMID- 26158758 TI - Synthesis of stable isotope-labeled epothilone D using a degradation reconstruction approach. AB - The stabilization of microtubules using epothilones represents a novel mechanism of action to treat Alzheimer's disease. Epothilone D is one such microtubule stabilizing drug that has been investigated by Bristol-Myers Squibb. An important step in the development process was the synthesis of a stable isotope-labeled analog for use in bioanalytical assays to accurately quantify the concentration of the drug in biological samples. A novel synthetic route to stable isotope labeled epothilone D is described. The synthetic route was based on a strategy to degrade epothilone B and then use that key intermediate to reconstruct stable isotope-labeled epothilone D. Epothilone B was treated with potassium osmate and sodium periodate. The thiazole moiety in epothilone B was efficiently cleaved to give (1S,3S,7S,10R,11S,12S,16R)-3-acetyl-7,11-dihydroxy-8,8,10,12,16-pentamethyl 4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione. The epoxide in the macrocyclic ring of that intermediate was cleanly removed by treatment with tungsten hexachloride and n-butyllithium to give the corresponding olefin (4S,7R,8S,9S,16S,Z)-16-acetyl-4,8-dihydroxy-5,5,7,9,13-pentamethyloxacyclohexadec 13-ene-2,6-dione. Bis(triethylsilyl) protection produced (4S,7R,8S,9S,16S,Z)-16 acetyl-5,5,7,9,13-pentamethyl-4,8-bis(triethylsilyloxy)-oxacyclohexadec-13-ene 2,6-dione. This intermediate was coupled to a stable isotope-labeled thiazole using a Wittig reaction as the key step to provide (13)C5, (15)N-labeled epothilone D. In summary, the synthesis was completed in nine total steps, only six of which involved isotopically labeled reagents. A total of 168 mg of (13)C5, (15)N-labeled epothilone D was prepared in an 8% overall yield from (13)C2, (15)N labeled thioacetamide and (13)C3-labeled ethyl bromopyruvate. PMID- 26158759 TI - Sleep-Related Breathing Disorders and the Chiari 1 Malformation. AB - The Chiari 1 malformation is characterized by > 5-mm herniation of the cerebellar tonsils through the foramen magnum. Consequent compression of the brain stem and nearby neuronal structures involved in respiratory control and maintenance of pharyngeal wall muscle tone may result in respiratory changes during sleep. These changes include respiratory failure and arrest, as well as sleep-related breathing disorders (ie, OSA and central sleep apnea). Although data have accrued on the significance of sleep-related breathing disorders in patients with the Chiari 1 malformation, many management questions remain unanswered. This article reviews the available literature on prevalence and management of sleep-related breathing disorders in patients with the Chiari 1 malformation. PMID- 26158760 TI - Silver(I)-Catalyzed Regioselective Construction of Highly Substituted alpha Naphthols and Its Application toward Expeditious Synthesis of Lignan Natural Products. AB - A novel route has been developed for regioselective synthesis of highly substituted alpha-naphthols, binaphthols, and anthracenol through silver(I) catalyzed C(sp(3))-H/C(sp)-H, C(sp(2))-H/C(sp)-H functionalization of beta ketoesters and alkynes, respectively, in a single step using water as a solvent. This protocol exhibited broad substrate scope and paved the way for synthesis of anticancer arylnaphthalene lignan natural products such as diphyllin, taiwanin E, and justicidin A with excellent selectivity. PMID- 26158761 TI - Thermal Desorption and Reaction of NO Adsorbed on Rhodium Cluster Ions Studied by Thermal Desorption Spectroscopy. AB - Cationic rhodium clusters, Rh(n)(+) (n = 4-8), were prepared in the gas phase by the laser ablation of a Rh rod. The Rh(n)(+) clusters were introduced into a reaction gas cell filled with nitric oxide (NO) diluted with He, where they were subjected to collisions with NO and He in a thermal equilibrium at 300 K. The NO molecules were found to adsorb sequentially on the Rh(n)(+) clusters forming Rh(n)(+)(NO)m. To examine the adsorption form and the reaction of NO, we heated Rh(n)(+)(NO)m in an extension tube located after the reaction gas cell and the thermal response of the clusters, desorption of the fragments, was recorded as a function of temperature (300-1000 K). The desorption of NO molecules was predominantly observed below 500 K, giving either Rh(n)(+)(NO)n+1 or Rh(n)(+)(NO)n+2, which indicates that there were NO molecules loosely adsorbed on the Rhn(+) clusters. Further desorption was found to proceed at higher temperatures (500-1000 K), whereby NO was released from the smaller clusters, Rh(n)(+) (n <= 5). In contrast, for the larger clusters (n >= 6), N2 release was clearly observed at high temperatures (>800 K). Thus, the reduction of NO occurred for larger clusters at higher temperatures. PMID- 26158762 TI - MiR-101 targets DUSP1 to regulate the TGF-beta secretion in sorafenib inhibits macrophage-induced growth of hepatocarcinoma. AB - Hepatocellular carcinoma (HCC)-associated macrophages accelerate tumor progression via growth factor release. Therefore, tumor-associated macrophages (TAMs)-initiated signaling cascades are potential therapeutic targets. To better understand anticancer effects of systemic HCC therapy, we studied sorafenib's effect on macrophage function, focusing on macrophage-related growth factor secretion. We found that dual specificity phosphatase 1 (DUSP1) is a direct target of miR-101. Transfection of miR-101 reduced DUSP1 induction in M2 macrophages and prolonged ERK1/2, p38 and JNK activation, whereas inhibition of miR-101 enhanced DUSP1 expression and decreased ERK1/2, p38 and JNK activation. miR-101 expression was decreased by sorafenib, and inhibition of PI3K/AKT blocked induction of miR-101 by LPS in M2 cells. M2 cells with greater TGF-beta and CD206 mRNA expression compared to M1 cells had increased hepatoma growth, metastases and EMT. Sorafenib inhibited miR-101 expression and enhanced DUSP1 expression and lowered TGF-beta and CD206 release in M2 cells, slowing macrophage-driven HCC. Our studies demonstrate miR-101 regulates macrophage innate immune responses to LPS via targeting DUSP1. Sorafenib alters macrophage polarization, reduces TGF beta driven cancer growth, metastases and EMT in vitro, and partially inhibits macrophage activation in vivo. Thus, macrophage modulation might explain the anticancer effects of sorafenib. PMID- 26158763 TI - Mastocytosis: a mutated KIT receptor induced myeloproliferative disorder. AB - Although more than 90% systemic mastocytosis (SM) patients express gain of function mutations in the KIT receptor, recent next generation sequencing has revealed the presence of several additional genetic and epigenetic mutations in a subset of these patients, which confer poor prognosis and inferior overall survival. A clear understanding of how genetic and epigenetic mutations cooperate in regulating the tremendous heterogeneity observed in these patients will be essential for designing effective treatment strategies for this complex disease. In this review, we describe the clinical heterogeneity observed in patients with mastocytosis, the nature of relatively novel mutations identified in these patients, therapeutic strategies to target molecules downstream from activating KIT receptor and finally we speculate on potential novel strategies to interfere with the function of not only the oncogenic KIT receptor but also epigenetic mutations seen in these patients. PMID- 26158766 TI - The time for an updated Canadian Food Guide has arrived. AB - Canada has published food guides since 1942 and the latest version, Eating Well with Canada's Food Guide (EWCFG), was released in 2007. The EWCFG is largely based on meeting nutrient requirements, while we are now in need of a food guide with strong guidance on the role of diet in the prevention of chronic diseases. This article systematically analyses the process and assumptions behind the EWCFG and presents suggestions for needed revisions to the next food guide. PMID- 26158764 TI - Extracellular galectin-3 programs multidrug resistance through Na+/K+-ATPase and P-glycoprotein signaling. AB - Galectin-3 (Gal-3, LGALS3) is a pleotropic versatile, 29-35 kDa chimeric gene product, and involved in diverse physiological and pathological processes, including cell growth, homeostasis, apoptosis, pre-mRNA splicing, cell-cell and cell-matrix adhesion, cellular polarity, motility, adhesion, activation, differentiation, transformation, signaling, regulation of innate/adaptive immunity, and angiogenesis. In multiple diseases, it was found that the level of circulating Gal-3 is markedly elevated, suggesting that Gal-3-dependent function is mediated by specific interaction with yet an unknown ubiquitous cell-surface protein. Recently, we showed that Gal-3 attenuated drug-induced apoptosis, which is one of the mechanisms underlying multidrug resistance (MDR). Here, we document that MDR could be mediated by Gal-3 interaction with the house-keeping gene product e.g., Na+/K+-ATPase, and P-glycoprotein (P-gp). Gal-3 interacts with Na+/K+-ATPase and induces the phosphorylation of P-gp. We also find that Gal-3 binds P-gp and enhances its ATPase activity. Furthermore Gal-3 antagonist suppresses this interaction and results in a decrease of the phosphorylation and the ATPase activity of P-gp, leading to an increased sensitivity to doxorubicin mediated cell death. Taken together, these findings may explain the reported roles of Gal-3 in diverse diseases and suggest that a combined therapy of inhibitors of Na+/K+-ATPase and Gal-3, and a disease specific drug(s) might be superior to a single therapeutic modality. PMID- 26158765 TI - CCAR2/DBC1 is required for Chk2-dependent KAP1 phosphorylation and repair of DNA damage. AB - Cell cycle and apoptosis regulator 2 (CCAR2, formerly known as DBC1) is a nuclear protein largely involved in DNA damage response, apoptosis, metabolism, chromatin structure and transcription regulation. Upon DNA lesions, CCAR2 is phosphorylated by the apical kinases ATM/ATR and this phosphorylation enhances CCAR2 binding to SIRT1, leading to SIRT1 inhibition, p53 acetylation and p53-dependent apoptosis. Recently, we found that also the checkpoint kinase Chk2 and the proteasome activator REGgamma are required for efficient CCAR2-mediated inhibition of SIRT1 and induction of p53-dependent apoptosis.Here, we report that CCAR2 is required for the repair of heterochromatic DNA lesions, as cells knock-out for CCAR2 retain, at late time-points after genotoxic treatment, abnormal levels of DNA damage-associated nuclear foci, whose timely resolution is reinstated by HP1beta depletion. Conversely, repair of DNA damages in euchromatin are not affected by CCAR2 absence.We also report that the impairment in heterochromatic DNA repair is caused by defective Chk2 activation, detectable in CCAR2 ablated cells, which finally impacts on the phosphorylation of the Chk2 substrate KAP1 that is required for the induction of heterochromatin relaxation and DNA repair.These studies further extend and confirm the role of CCAR2 in the DNA damage response and DNA repair and illustrate a new mechanism of Chk2 activity regulation. Moreover, the involvement of CCAR2 in the repair of heterochromatic DNA breaks suggests a new role for this protein in the maintenance of chromosomal stability, which is necessary to prevent cancer formation. PMID- 26158767 TI - LiSiCA: A Software for Ligand-Based Virtual Screening and Its Application for the Discovery of Butyrylcholinesterase Inhibitors. AB - We developed LiSiCA (ligand similarity using clique algorithm)--ligand-based virtual screening software that uses a fast maximum clique algorithm to find two- and three-dimensional similarities between pairs of molecules and applied it to the discovery of novel potent butyrylcholinesterase inhibitors. LiSiCA, which runs in parallel on multiple processor cores, was successfully tested on the Database of Useful Decoys-Enhanced, to evaluate its ability to discriminate active molecules from decoys. We then applied LiSiCA for the discovery of novel inhibitors of human butyrylcholinesterase, a promising anti-Alzheimer target, using a known inhibitor as the reference compound. We demonstrated that LiSiCA is capable of finding potent nanomolar inhibitors, whose scaffolds differed from the reference compound, thus proving its ability for scaffold hopping and usefulness in drug discovery. PMID- 26158768 TI - Aharonov-Bohm oscillations in a quasi-ballistic three-dimensional topological insulator nanowire. AB - Aharonov-Bohm oscillations effectively demonstrate coherent, ballistic transport in mesoscopic rings and tubes. In three-dimensional topological insulator nanowires, they can be used to not only characterize surface states but also to test predictions of unique topological behaviour. Here we report measurements of Aharonov-Bohm oscillations in (Bi1.33Sb0.67)Se3 that demonstrate salient features of topological nanowires. By fabricating quasi-ballistic three-dimensional topological insulator nanowire devices that are gate-tunable through the Dirac point, we are able to observe alternations of conductance maxima and minima with gate voltage. Near the Dirac point, we observe conductance minima for zero magnetic flux through the nanowire and corresponding maxima (having magnitudes of almost a conductance quantum) at magnetic flux equal to half a flux quantum; this is consistent with the presence of a low-energy topological mode. The observation of this mode is a necessary step towards utilizing topological properties at the nanoscale in post-CMOS applications. PMID- 26158769 TI - The Effect of Chinese Traditional Exercise-Baduanjin on Physical and Psychological Well-Being of College Students: A Randomized Controlled Trial. AB - BACKGROUND: The physical and mental health of college students tends to continuously decline around the world, therefore, it is important to improve their health during college period. Baduanjin, a traditional Chinese exercise which combines movements with breath and mind, may be one of the selectable effective exercises. However, the effect of Baduanjin exercise on college students has not been established. In this study, we systematically assessed the effectiveness and safety of Baduanjin exercise on physical and mental health of college students by a rigorous randomized, parallel-controlled design. METHODS: A total of 222 college students from Fujian University of Traditional Chinese Medicine were recruited and randomly allocated at an equal ratio into control or Baduanjin training. Participants in control group were informed to maintain their original activity habit, and those in Baduanjin exercise group received a 12-week Baduanjin exercise training with a frequency of 1 hour per day and 5 days per week on the basis of their original activity habit. The physical and psychological outcomes, including lumbar muscle strength, lower limb proprioception function, physical fitness, as well as self-reported symptom intensity, stress, self-esteem, mood, quality of life, quality of sleep, and adverse events, were evaluated at baseline, 13 weeks (at the end of 12-week intervention), and 25 weeks (after the 12-week follow-up period). Intention-to treat analysis was performed for the above outcomes. RESULTS: Compared with controls, significant improvements in Baduanjin exercise group at the end of 12 week intervention period were found on lower limb proprioception function (the rate of average trace error on right lower limb (%): control 23.50+/-5.50, Baduanjin 21.92+/-6.54, P=0.004; the rate of average trace error on left lower limb (%): control 22.32+/-6.62, Baduanjin 20.63+/-4.62, P=0.046), cardiorespiratory endurance (step test index: control 47.66+/-5.94, Baduanjin 50.07+/-9.30, P=0.025), flexibility (control 14.35+/-7.26cm, Baduanjin 15.39+/ 6.43cm, P=0.009) and explosive force of lower limb (standing long jump test (m): control 1.77+/-0.24, Baduanjin 1.79+/-0.22, P=0.005 for adjustment baseline) in physical outcomes, and attention (Schulte Grid test (second): control 210.4+/ 51.15, Baduanjin 192.4+/-47.14, P=0.034) in mental outcome. Lumbar muscle strength in Baduanjin group had been moderately enhanced but no significant difference compared to controls. No significant changes in other physical and mental outcomes, including vital capacity, blood pressure, heart rate, hand grip force, self-symptom intensity, stress, self-efficacy, quality of life, and quality of sleep, were found between groups. No adverse event was reported during the study period. CONCLUSION: Regular Baduanjin exercise had an advantage for college students on improvement of lower limb proprioception, enhance of cardiorespiratory endurance, flexibility, explosive force of lower limb and attention, compared with usual exercise. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-13003329 http://www.chictr.org. PMID- 26158770 TI - Development and pilot validation of a sensory reactivity scale for adults with high functioning autism spectrum conditions: Sensory Reactivity in Autism Spectrum (SR-AS). AB - BACKGROUND: Unusual reactions to sensory stimuli are experienced by 90-95% of people with an autism spectrum condition (ASC). Self-reported sensory reactivity in ASC has mainly been measured with generic questionnaires developed and validated on data from the general population. Interest in sensory reactivity in ASC increased after the inclusion of hyper- and hypo-reactivity together with unusual sensory interest as diagnostic markers of ASC in the DSM-5. AIMS: To develop and pilot validate a self-report questionnaire designed from first-hand descriptions of the target group of adults diagnosed with high functioning ASC. Psychometric properties of the questionnaire were evaluated on a sample of participants with ASC diagnoses (N = 71) and a random sample from the general population (N = 162). RESULTS: The Sensory Reactivity in Autism Spectrum (SR-AS is intended to be used as a screening tool in diagnostic processes with adults and for support in adapting compensating strategies and environmental adjustments. The internal consistency was high for both the SR-AS and its subscales. The total scale Cronbach's alpha was 0.96 and the subscales alphas were >= 0.80. Confirmatory factor analysis (CFA) showed best fit for a four factor model of inter-correlated factors: hyper and hypo-reactivity, strong sensory interest and a sensory/motor factor. The questionnaire discriminated well between ASC-diagnosed participants and participants from the general population. CONCLUSIONS: The SR-AS displayed good internal consistency and discriminatory power and promising factorial validity. PMID- 26158771 TI - Polycyclic Aromatic Hydrocarbons in the Mainstream Smoke of Popular U.S. Cigarettes. AB - The mainstream smoke yields of 14 polycyclic aromatic hydrocarbons (PAHs) were determined for 50 commercial U.S. cigarettes using a validated GC/MS method with the International Organization of Standardization (ISO) and Canadian Intense (CI) smoking machine regimens. PAH mainstream smoke deliveries vary widely among the commercial cigarettes with the ISO smoking regimen primarily because of differing filter ventilation. The more abundant, lower molecular weight PAHs such as naphthalene, fluorene, and phenanthrene predominantly comprise the total PAH yields. In contrast, delivery yields of high molecular weight PAHs such as benzo[b]fluoranthene, benzo[e]pyrene, benzo[k]fluoranthene, and benzo[a]pyrene (BaP) are much lower. Comparative analysis of PAHs deliveries shows brand specific differences. Correlation analysis shows strong positive associations between BaP and most of the other PAHs as well as total PAHs. The results suggest that BaP may be a representative marker for other PAH constituents in cigarette smoke generated from similarly blended tobacco, particularly those PAHs with similar molecular weights and chemical structures. PMID- 26158772 TI - Hypothalamic inflammation and food intake regulation during chronic illness. AB - Anorexia is a common symptom in chronic illness. It contributes to malnutrition and strongly affects survival and quality of life. A common denominator of many chronic diseases is an elevated inflammatory status, which is considered to play a pivotal role in the failure of food-intake regulating systems in the hypothalamus. In this review, we summarize findings on the role of hypothalamic inflammation on food intake regulation involving hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC). Furthermore, we outline the role of serotonin in the inability of these peptide based food-intake regulating systems to respond and adapt to changes in energy metabolism during chronic disease. PMID- 26158773 TI - Current advances and challenges in the development of Acinetobacter vaccines. AB - Acinetobacter baumannii is a major cause of healthcare-associated infections worldwide with high morbidity and mortality. The clinical treatment of A. baumannii infections has become increasingly difficult because of the rapid emerging of multidrug and extremely drug resistant strains. Thus, there is an urgent need for the development of novel intervention strategies to combat this multidrug-resistant pathogen. Vaccine is one of the most effective medical measures for infection control and is likely to overcome the development of multidrug resistance by A. baumannii. Here we discussed the recent advances and potential challenges in development of A. baumannii vaccines with a focus on the 3 most important steps in the preclinical vaccine development: antigen selection, immune correlates of protection, and animal models for efficacy evaluation. PMID- 26158774 TI - Agriculture intensifies soil moisture decline in Northern China. AB - Northern China is one of the most densely populated regions in the world. Agricultural activities have intensified since the 1980s to provide food security to the country. However, this intensification has likely contributed to an increasing scarcity in water resources, which may in turn be endangering food security. Based on in-situ measurements of soil moisture collected in agricultural plots during 1983-2012, we find that topsoil (0-50 cm) volumetric water content during the growing season has declined significantly (p < 0.01), with a trend of -0.011 to -0.015 m(3) m(-3) per decade. Observed discharge declines for the three large river basins are consistent with the effects of agricultural intensification, although other factors (e.g. dam constructions) likely have contributed to these trends. Practices like fertilizer application have favoured biomass growth and increased transpiration rates, thus reducing available soil water. In addition, the rapid proliferation of water-expensive crops (e.g., maize) and the expansion of the area dedicated to food production have also contributed to soil drying. Adoption of alternative agricultural practices that can meet the immediate food demand without compromising future water resources seem critical for the sustainability of the food production system. PMID- 26158776 TI - A (pentafluoroethyl)(trifluoromethyl)carbene complex of iridium and reductive activation of its sp(3)alpha, beta, and gamma carbon-fluorine bonds to give perfluoro-2-butyne, perfluoro-1,2,3-butatriene and perfluoro-1-irida-2-methyl-2 cyclobutene) complexes. AB - The (pentafluoroethyl)(trifluoromethyl)carbene complex Cp*Ir(CO)[[double bond, length as m-dash]C(CF3)(C2F5)] was synthesized by the reductive activation of the alpha-C-F bond in the perfluoro-sec-butyl-iridium complex Cp*Ir(CO)[CF(CF3)(C2F5)](I) with Na/Pb alloy. This compound exists as two geometric isomers in solution; the structure of one isomer has been determined by a single crystal X-ray diffraction study and contains two independent molecules in the asymmetric unit. Further reduction of this carbene complex with Na/Pb alloy afforded the perfluoro-2-butyne iridium complex Cp*Ir(CO)(eta(2) CF3C[triple bond, length as m-dash]CCF3) by an overall 2-electron reduction and elimination of two beta-fluorides. When magnesium graphite was utilized as the reducing agent for the further reduction, Cp*Ir(CO)(eta(2)-CF3C[triple bond, length as m-dash]CCF3) was produced as a minor product and the major product was the perfluoroiridacyclobutene complex Cp*Ir(CO)(eta(2,4)-CF3CCFCF2) resulting from a gamma-C-F bond activation. Direct reduction of the precursor Cp*Ir(CO)[CF(CF3)(C2F5)](i) with magnesium graphite generated the tetrafluorobutatriene iridium complex Cp*Ir(CO)(eta(2,3)-CF2[double bond, length as m-dash]C[double bond, length as m-dash]C[double bond, length as m-dash]CF2) along with the perfluoro-2-butyne complex and perfluoroiridacyclobutene complexes in a ratio of 1 : 2 : 6. These reductive inner-sphere pathways to unsaturated fluorocarbon ligands illustrate that carbon-fluorine bond activation can take place at alpha-, beta- and gamma-carbons but that selectivity in these heterogeneous reductions is difficult to control, with a variety of fluoride eliminations possible for complex perfluoroalkyl ligands. Density Functional Theory (DFT/B3LYP-D3/LACV3P**++) is used to explore the relative energetics of products and intermediates in these reactions. PMID- 26158777 TI - DFT-Derived Force Fields for Modeling Hydrocarbon Adsorption in MIL-47(V). AB - Generic force fields such as UFF and DREIDING are widely used for predicting molecular adsorption and diffusion in metal-organic frameworks (MOFs), but the accuracy of these force fields is unclear. We describe a general framework for developing transferable force fields for modeling the adsorption of alkanes in a nonflexible MIL-47(V) MOF using periodic density functional theory (DFT) calculations. By calculating the interaction energies for a large number of energetically favorable adsorbate configurations using DFT, we obtain a force field that gives good predictions of adsorption isotherms, heats of adsorption, and diffusion properties for a wide range of alkanes and alkenes in MIL-47(V). The force field is shown to be transferable to related materials such as MIL 53(Cr) and is used to calculate the free-energy differences for the experimentally observed phases of MIL-53(Fe). PMID- 26158775 TI - Differential Contribution of Acute and Chronic Inflammation to the Development of Murine Mammary 4T1 Tumors. AB - Based on the notion that inflammation favors tumorigenesis, our experiments comparatively assessed the influence of acute and chronic inflammation on the development of a murine mammary tumor (4T1). In addition, we characterized angiogenic and inflammatory markers in the tumor tissue and systemically. Subcutaneous implantation of polyether-polyurethane sponge discs in Balb/c mice was used to host 4T1 tumor cells (1x10(6)), which were inoculated intraimplant 24 h or 10 days post implantation. Flow cytometric analysis of enzyme-digested implants revealed that, after 24 hours, the population of leukocytes was primarily characterized by neutrophils (42.53% +/- 8.45) and monocytes (37.53% +/ 7.48), with some lymphocytes (16.27% +/- 4.0) and a few dendritic cells (1.82% +/- 0.36). At 10 days, macrophages were predominant (37.10% +/- 4.54), followed by lymphocytes (28.1% +/- 4.77), and monocytes (22.33% +/- 3.05), with some dendritic cells (13.60% +/- 0.55) and neutrophils (11.07% +/- 2.27). A mammary tumor grown in a chronic inflammatory environment was 2-fold when compared with one grown in acute inflammation and 5-fold when compared with tumor alone. The levels of pro-angiogenic cytokine (VEGF-Vascular Endothelial Growth Factor) were higher in implant-bearing tumor when 4T1 cells were grown in 10-day old implants as compared to the VEGF levels of the two other groups. Overall, the levels of the inflammatory markers evaluated (NAG -N-acetylglucosaminidase, TNF-alpha-Tumor Necrosis Factor-alpha) were higher in both groups of implant-bearing tumors and in serum from those animals when compared with the tumor alone levels. This inflammation-related difference in tumor growth may provide new insights into the contribution of different inflammatory cell populations to cancer progression. PMID- 26158778 TI - Matched trauma: The role of parents' and children's shared history of childhood domestic violence exposure in parents' report of children's trauma-related symptomatology. AB - Parents' childhood experiences of trauma may influence their reports of their children's behavior, and this may be particularly true when children are also traumatized. The present study proposed and tested a matched trauma hypothesis, positing that compared to parents without a childhood history of witnessing domestic violence (DV), parents with a childhood history of witnessing DV may report their children's trauma-related symptomatology differently following children's exposure to DV. Of 137 included parents (M age = 32 years; 93% mothers), 81 reported witnessing childhood DV (matched group), whereas 56 reported no childhood DV exposure (nonmatched comparison group). All parents reported on their 3- to 6-year-old children's dissociation and posttraumatic stress symptoms following children's DV exposure. An analysis of covariance controlling for parental life stress, dissociation symptoms, and other childhood traumatic events revealed that parents who witnessed childhood DV reported significantly fewer child dissociation symptoms than comparison parents. No difference was found for parents' reports of children's posttraumatic stress symptoms. Exploratory analyses on a subsample of children with teacher reports of child dissociation symptoms (n = 75) revealed that the strength of the association between parent and teacher reports of dissociation symptoms was moderated by matched versus nonmatched group membership. Findings suggest the importance of considering a parent's history of trauma when using parents as informants for children's trauma symptoms. PMID- 26158779 TI - A bioactive cycloartane triterpene from Garcinia hombroniana. AB - The dichloromethane bark extract of Garcinia hombroniana yielded one new cycloartane triterpene; (22Z,24E)-3beta-hydroxycycloart-14,22,24-trien-26-oic acid (1) together with five known compounds: garcihombronane G (2), garcihombronane J (3), 3beta acetoxy-9alpha-hydroxy-17,14-friedolanostan-14,24 dien-26-oic acid (4), (22Z, 24E)-3beta, 9alpha-dihydroxy-17,14-friedolanostan 14,22,24-trien-26-oic acid (5) and 3beta, 23alpha-dihydroxy-17,14-friedolanostan 8,14,24-trien-26-oic acid (6). Their structures were established by the spectral techniques of NMR and ESI-MS. These compounds together with some previously isolated compounds; garcihombronane B (7), garcihombronane D (8) 2,3',4,5' tetrahydroxy-6-methoxybenzophenone (9), volkensiflavone (10), 4''-O-methyll volkensiflavone (11), volkensiflavone-7-O-glucopyranoside (12), volkensiflavone-7 O-rhamnopyranoside (13), Morelloflavone (14), 3''-O-methyl-morelloflavone (15) and morelloflavone-7-O-glucopyranoside (16) were evaluated for cholinesterase enzymes inhibitory activities using acetylcholinesterase and butyrylcholinesterase. In these activities, compounds 1-9 showed good dual inhibition on both the enzymes while compounds 10-16 did not reasonably contribute to both the cholinesterases inhibitory effects. PMID- 26158780 TI - Two routes to senescence revealed by real-time analysis of telomerase-negative single lineages. AB - In eukaryotes, telomeres cap chromosome ends to maintain genomic stability. Failure to maintain telomeres leads to their progressive erosion and eventually triggers replicative senescence, a pathway that protects against unrestricted cell proliferation. However, the mechanisms underlying the variability and dynamics of this pathway are still elusive. Here we use a microfluidics-based live-cell imaging assay to investigate replicative senescence in individual Saccharomyces cerevisiae cell lineages following telomerase inactivation. We characterize two mechanistically distinct routes to senescence. Most lineages undergo an abrupt and irreversible switch from a replicative to an arrested state, consistent with telomeres reaching a critically short length. In contrast, other lineages experience frequent and stochastic reversible arrests, consistent with the repair of accidental telomere damage by Pol32, a subunit of polymerase delta required for break-induced replication and for post-senescence survival. Thus, at the single-cell level, replicative senescence comprises both deterministic cell fates and chaotic cell division dynamics. PMID- 26158781 TI - Deploying FLAREs to Visualize Functional Outcomes of Host-Pathogen Encounters. PMID- 26158782 TI - Reversible Lithium Storage in Manganese 1,3,5-Benzenetricarboxylate Metal-Organic Framework with High Capacity and Rate Performance. AB - Metal organic frameworks (MOFs) with diverse structural chemistry are being projected as futuristic electrode materials for Li-ion batteries. In this work, we report synthesis of Mn-1,3,5-benzenetricarboxylate MOF by a simple solvothermal method and its application as an anode material for the first time. Scanning electron microscopy of the synthesized MOF shows a bar shaped morphology where these bars, about 1 MUm wide and of varied lengths between 2 and 20 MUm, are made of porous sheets containing mesoporous walls and macroporous channels. The MOF anode, when examined in the potential window of 0.01-2.0 V versus Li/Li(+), shows high specific capacities of 694 and 400 mAh g(-1) at current densities of 0.1 and 1.0 A g(-1) along with good cyclability, retention of capacity, and sustenance of the MOF network. Ex situ X-ray diffraction, Fourier transform infrared, and X-ray photoelectron spectroscopy studies on the electrode material at different states of charge suggest that the usual conversion reaction for Li storage might not be applicable in this case. Conjugated carboxylates being weakly electron withdrawing ligands with a stronger pi-pi interaction, a probable alternative Li storage mechanism has been proposed that involves the organic moiety. The present results show promise for applying Mn-1,3,5 benzenetricarboxylate MOF as high performance <2 V anode. PMID- 26158783 TI - The 10-year effectiveness of combination antiretroviral treatment in perinatally HIV-infected children participating in Thailand's National Access Program. AB - BACKGROUND: The National Access to Antiretroviral Program for People Living with HIV/AIDS was launched in Thailand in 2002. HIV-infected, antiretroviral-naive, severely immunosuppressed children were initiated on highly active combination antiretroviral treatment (cART). This study aimed to determine the long-term effectiveness of cART. METHODS: Data were extracted from medical records. Primary end points were mortality rate, proportion of children who remained on first-line cART regimen and children with plasma HIV RNA level (pVL) <50 copies/ml at week 520. RESULTS: From August 2002 to July 2003, 107 children were enrolled. The baseline median age was 7.6 years (IQR 5.7-10.0), the median CD4(+) T-cell count was 60 cells/mm(3) (IQR 21-272) and the median pVL was 5.37 log10 copies/ml (IQR 5.01-5.76). The mortality rate during and after the first year was 3.7 and 0.006 deaths/100 person-years, respectively. At week 520, 90 (84%) continued to be actively followed. Their median age was 17.8 years (IQR 15.8-19.8). 73 (81% as treated) remained on the first-line regimen, while 18 (20%) had switched to a second-line cART regimen, at the median time of 272 weeks (IQR 256-363) after the first-line cART initiation. 69 (77%) had pVL<50 copies/ml and the median CD4(+) T cell count was 636 cells/mm(3) (IQR 466-804). 83 (92%) and 64 (71%) had CD4(+) T cell counts >=200 and >500 cells/mm(3), respectively. CONCLUSIONS: Long-term virological control, favourable immunological outcomes and healthy survival was achieved in severely immunosuppressed, perinatally HIV-infected children who started first-line NNRTI-based cART. Continuing surveillance for long-term complications is warranted. PMID- 26158784 TI - Direct Determination of Trace Antimony in Natural Waters by Photochemical Vapor Generation ICPMS: Method Optimization and Comparison of Quantitation Strategies. AB - A novel and sensitive approach for the accurate determination of antimony (Sb) in natural waters is described using photochemical vapor generation (PVG) coupled with inductively coupled plasma mass spectrometry (ICPMS) for detection. Utilizing a unique flow-through photochemical reactor capable of subjecting the samples to deep-UV (185 nm) radiation, generation efficiency was found to be independent of whether Sb(III), Sb(V), or organometallic species [trimethyltantimony(V)dibromine, TMSb(V)] were present, eliminating the shortcoming of Sb species depended sensitivity encountered during direct solution nebulization by ICPMS. Furthermore, the potentially severe matrix effect from seawater was efficiently eliminated by using a mixture of 5% (v/v) formic and 15% acetic acids (v/v) as the photochemical reductant, making direct determination of Sb in seawater feasible. The proposed method provides a 15-fold improvement in sensitivity over direct solution nebulization. A method detection limit of 0.0006 ng g(-1) based on external calibration was obtained (0.0002 ng g(-1) for isotope dilution), yielding a 15-fold improvement over that for direct solution nebulization. Accuracy is demonstrated by analysis of two water certified reference materials (CRMs, e.g., SLRS-6 and NIST 1640a) with satisfying results. In addition, spike recoveries of 100.6 +/- 5.5% and 100.8 +/- 3.8% (standard deviation, n = 3) were obtained for NASS-6 and CASS-5 seawater CRMs, respectively, since no certified values for Sb has been established for these materials. The performance of several calibration strategies, including double isotope dilution (ID), multiple and single-point gravimetric standard additions with internal standardization, as well as multiple and single-point gravimetric standard additions alone was examined. High precision of determination of Sb in four natural water samples (0.51-1.4%) was realized based on ID calibration, whereas one-point gravimetric standard addition calibration with internal standardization provided precisions of 1.6% and 3.3% at 0.22 and 0.44 ng g(-1) levels, respectively, in seawater. PMID- 26158786 TI - Ruthenium-Catalyzed Formal Dehydrative [4 + 2] Cycloaddition of Enamides and Alkynes for the Synthesis of Highly Substituted Pyridines: Reaction Development and Mechanistic Study. AB - Reported herein is a ruthenium-catalyzed formal dehydrative [4 + 2] cycloaddition of enamides and alkynes, representing a mild and economic protocol for the construction of highly substituted pyridines. Notably, the features of broad substrate scope, high efficiency, good functional group tolerance, and excellent regioselectivities were observed for this reaction. Density functional theory (DFT) calculations and experiments have been carried out to understand the mechanism and regiochemistry. DFT calculations suggested that this formal dehydrative [4 + 2] reaction starts with a concerted metalation deprotonation of the enamide by the acetate group in the Ru catalyst, which generates a six membered ruthenacycle intermediate. Then alkyne inserts into the Ru-C bond of the six-membered ruthenacycle, giving rise to an eight-membered ruthenacycle intermediate. The carbonyl group (which comes originally from the enamide substrate and is coordinated to the Ru center in the eight-membered ruthenacycle intermediate) then inserts into the Ru-C bond to give an intermediate, which produces the final pyridine product through further dehydration. Alkyne insertion step is a regio-determining step and prefers to have the aryl groups of the used alkynes stay away from the catalyst in order to avoid repulsion of aryl group with the enamide moiety in the six-membered ruthenacycle and to keep the conjugation between the aryl group and the triple C-C bond of the alkynes. Consequently, the aryl groups of the used alkynes are in the beta-position of the final pyridines, and the present reaction has high regioselectivity. PMID- 26158787 TI - Zipf's Law for Word Frequencies: Word Forms versus Lemmas in Long Texts. AB - Zipf's law is a fundamental paradigm in the statistics of written and spoken natural language as well as in other communication systems. We raise the question of the elementary units for which Zipf's law should hold in the most natural way, studying its validity for plain word forms and for the corresponding lemma forms. We analyze several long literary texts comprising four languages, with different levels of morphological complexity. In all cases Zipf's law is fulfilled, in the sense that a power-law distribution of word or lemma frequencies is valid for several orders of magnitude. We investigate the extent to which the word-lemma transformation preserves two parameters of Zipf's law: the exponent and the low frequency cut-off. We are not able to demonstrate a strict invariance of the tail, as for a few texts both exponents deviate significantly, but we conclude that the exponents are very similar, despite the remarkable transformation that going from words to lemmas represents, considerably affecting all ranges of frequencies. In contrast, the low-frequency cut-offs are less stable, tending to increase substantially after the transformation. PMID- 26158788 TI - Effects of shear rate and suspending viscosity on deformation and frequency of red blood cells tank-treading in shear flows. AB - The tank-treading rotation of red blood cells (RBCs) in shear flows has been studied extensively with experimental, analytical, and numerical methods. Even for this relatively simple system, complicated motion and deformation behaviors have been observed, and some of the underlying mechanisms are still not well understood. In this study, we attempt to advance our knowledge of the relationship among cell motion, deformation, and flow situations with a numerical model. Our simulation results agree well with experimental data, and confirm the experimental finding of the decrease in frequency/shear-rate ratio with shear rate and the increase of frequency with suspending viscosity. Moreover, based on the detailed information from our simulations, we are able to interpret the frequency dependency on shear rate and suspending viscosity using a simple two fluid shear model. The information obtained in this study thus is useful for understanding experimental observations of RBCs in shear and other flow situations; the good agreement to experimental measurements also shows the potential usefulness of our model for providing reliable results for microscopic blood flows. PMID- 26158790 TI - TiO2 nanotubes with ultrathin walls for enhanced water splitting. AB - We demonstrate, for the first time, the synthesis of titania nanotubes with ultrathin (3-5 nm) wall thickness. As revealed by the incident photon-to-current collection efficiency (IPCE) and electrochemical impedance spectroscopy measurements, the ultrathin walls, less than the charge carrier diffusion length, were essential to ensure fast and efficient charge carrier collection. PMID- 26158792 TI - Highlights from the Biennial International Congress on Schizophrenia Research (ICOSR), March 28-April 1, 2015. AB - The 2015 International Congress on Schizophrenia Research, held in Colorado Springs, Colorado, attracted over 1,000 attendees from March 28-April 1, 2015. With the gracious assistance of Congress directors Carol Tamminga and Chuck Schulz, as well as meeting staff Dorothy Denton and Cristan Tamminga, we bring you the following reports on various Congress sessions concerning approaches to prevention in schizophrenia and social cognition. PMID- 26158793 TI - Sources of social support and community integration among persons with serious mental illnesses in Korea. AB - BACKGROUND: Community integration is an important component of recovery for persons with serious mental illnesses (SMI). However, persons with SMI often experience barriers in using community resources, participating in community activities, and developing interactions with neighbors and other community members. AIMS: This study examines the association between different sources of social support, including family, friends and mental health services providers, and three dimensions of community integration. METHOD: A sample of 399 persons with SMI was interviewed from community-based mental health service agencies in South Korea. RESULTS: Family support and friendship support positively influenced all three aspects of community integration. More support from mental health professionals was associated with increased perceived accessibility to community resources but decreased involvement in community activities. CONCLUSION: Recommendations are made in supporting the role of natural networks and in advocating for a consumer-centered approach to service delivery. PMID- 26158795 TI - Anticancer Effects of Extracts from the Fruit of Morinda Citrifolia (Noni) in Breast Cancer Cell Lines. AB - Morinda citrifolia L. (NONI) fruits have been used for thousands of years for the treatment of many health problems including cancer, cold, diabetes, flu, hypertension, and pain. Plant extracts have reported several therapeutic benefits, but extraction of individual compound from the extract often exhibits limited clinical utility as the synergistic effect of various natural ingredients gets lost. They generally constitute polyphenols and flavonoids. Studies have suggested that these phytochemicals, especially polyphenols, display high antioxidant properties, which help to reduce the risk of degenerative diseases, such as cancer and cardiovascular diseases. Several in-vitro and in-vivo studies have shown that Noni fruits have antioxidant, anti-inflammatory, anti-dementia, liver-protective, anticancer, analgesic, and immunomodulatory effects. Till date about 7 in vitro cancer studies have been done, but a detailed in vitro study including cell cycle and caspase activation assay on breast cancer cell line has not been done. In the present study different Noni fruit fractions have tested on cancer cell lines MCF-7, MDA-MB-231 (breast adenocarcinoma) and one non-cancer cell line HEK-293 (Human embryonic kidney). Out of which ethylacetate extract showed a higher order of in vitro anticancer activity profile. The ethylacetate extract strongly inhibited the proliferation of MCF-7, MDA-MB-231 and HEK-293 cell lines with IC50 values of 25, 35, 60 ug/ml respectively. The extract showed increase in apoptotic cells in MCF-7 and MDA-MB-231 cells and arrested the cell cycle in the G1/S phase in MCF-7 and G0/G1 phase in MDA-MB-231 cells. Noni extract also decreases the intracellular ROS generation and mitochondrial membrane potential. PMID- 26158794 TI - A Pharmacokinetic/Pharmacodynamic Drug-Drug Interaction Study of Tofogliflozin (a New SGLT2 Inhibitor) and Selected Anti-Type 2 Diabetes Mellitus Drugs. AB - OBJECTIVE: Tofogliflozin is an oral hypoglycemic agent with a novel mechanism of action that reduces blood glucose levels by promoting glucose excretion in urine, achieved by selectively inhibiting sodium-glucose co-transporter 2 (SGLT2). We evaluated the effects of several selected anti-type 2 diabetes mellitus (T2DM) drugs-glimepiride, metformin, sitagliptin, pioglitazone, miglitol, nateglinide, and voglibose-on the pharmacokinetics and pharmacodynamics of tofogliflozin, and the effects of tofogliflozin on the pharmacokinetics of these anti-T2DM drugs in healthy male volunteers. METHODS: A single dose of either tofogliflozin alone, one of the anti-T2DM drugs alone, or co-administration of tofogliflozin and the anti-T2DM drug was administered to 108 healthy men. Cmax, AUCinf, and cumulative urine glucose excretion after co-administration of tofogliflozin and each of the anti-T2DM drugs was evaluated relative to the values of those parameters after administration of each drug alone. RESULTS: None of the anti-T2DM drugs had any effect on tofogliflozin exposure. Tofogliflozin had no or little effect on the exposure of any anti-T2DM drug. No anti-T2DM drug had any major effect on the cumulative urine glucose excretion induced by tofogliflozin. There were no safety concerns evident after administration of any drug alone or in co-administration. CONCLUSIONS: Neither the pharmacokinetics nor the pharmacodynamics of tofogliflozin was affected by any of the anti-T2DM drugs evaluated in this study, nor was the pharmacokinetics of any of the anti-T2DM drugs affected by tofogliflozin in healthy male volunteers. PMID- 26158796 TI - Trimethylaluminum and Oxygen Atomic Layer Deposition on Hydroxyl-Free Cu(111). AB - Atomic layer deposition (ALD) of alumina using trimethylaluminum (TMA) has technological importance in microelectronics. This process has demonstrated a high potential in applications of protective coatings on Cu surfaces for control of diffusion of Cu in Cu2S films in photovoltaic devices and sintering of Cu based nanoparticles in liquid phase hydrogenation reactions. With this motivation in mind, the reaction between TMA and oxygen was investigated on Cu(111) and Cu2O/Cu(111) surfaces. TMA did not adsorb on the Cu(111) surface, a result consistent with density functional theory (DFT) calculations predicting that TMA adsorption and decomposition are thermodynamically unfavorable on pure Cu(111). On the other hand, TMA readily adsorbed on the Cu2O/Cu(111) surface at 473 K resulting in the reduction of some surface Cu(1+) to metallic copper (Cu(0)) and the formation of a copper aluminate, most likely CuAlO2. The reaction is limited by the amount of surface oxygen. After the first TMA half-cycle on Cu2O/Cu(111), two-dimensional (2D) islands of the aluminate were observed on the surface by scanning tunneling microscopy (STM). According to DFT calculations, TMA decomposed completely on Cu2O/Cu(111). High-resolution electron energy loss spectroscopy (HREELS) was used to distinguish between tetrahedrally (Altet) and octahedrally (Aloct) coordinated Al(3+) in surface adlayers. TMA dosing produced an aluminum oxide film, which contained more octahedrally coordinated Al(3+) (Altet/Aloct HREELS peak area ratio ~ 0.3) than did dosing O2 (Altet/Aloct HREELS peak area ratio ~ 0.5). After the first ALD cycle, TMA reacted with both Cu2O and aluminum oxide surfaces in the absence of hydroxyl groups until film closure by the fourth ALD cycle. Then, TMA continued to react with surface Al-O, forming stoichiometric Al2O3. O2 half-cycles at 623 K were more effective for carbon removal than O2 half-cycles at 473 K or water half-cycles at 623 K. The growth rate was approximately 3-4 A/cycle for TMA+O2 ALD (O2 half-cycles at 623 K). No preferential growth of Al2O3 on the steps of Cu(111) was observed. According to STM, Al2O3 grows homogeneously on Cu(111) terraces. PMID- 26158798 TI - Feasibility and acceptability of an audio computer-assisted self-interview version of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) in primary care patients. AB - BACKGROUND: This study explores the feasibility and acceptability of a computer self-administered approach to substance use screening from the perspective of primary care patients. METHODS: Forty-eight patients from a large safety net hospital in New York City completed an audio computer-assisted self-interview (ACASI) version of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and a qualitative interview to assess feasibility and acceptability, comprehension, comfort with screening questions, and preferences for screening mode (interviewer or computer). Qualitative data analysis organized the participants' feedback into major themes. RESULTS: Participants overwhelmingly reported being comfortable with the ACASI ASSIST. Mean administration time was 5.2 minutes (range: 1.6-14.8 minutes). The major themes from the qualitative interviews were (1) ACASI ASSIST is feasible and acceptable to patients, (2) Social stigma around substance use is a barrier to patient disclosure, and (3) ACASI screening should not preclude personal interaction with providers. CONCLUSIONS: The ACASI ASSIST is an appropriate and feasible approach to substance use screening in primary care. Because of the highly sensitive nature of substance use, screening tools must explain the purpose of screening, assure patients that their privacy is protected, and inform patients of the opportunity to discuss their screening results with their provider. PMID- 26158803 TI - King v Burwell: Subsidizing US Health Insurance for Low- and Middle-Income Individuals. PMID- 26158802 TI - Galectin CvGal2 from the Eastern Oyster (Crassostrea virginica) Displays Unique Specificity for ABH Blood Group Oligosaccharides and Differentially Recognizes Sympatric Perkinsus Species. AB - Galectins are highly conserved lectins that are key to multiple biological functions, including pathogen recognition and regulation of immune responses. We previously reported that CvGal1, a galectin expressed in phagocytic cells (hemocytes) of the eastern oyster (Crassostrea virginica), is hijacked by the parasite Perkinsus marinus to enter the host, where it causes systemic infection and death. Screening of an oyster hemocyte cDNA library revealed a novel galectin, which we designated CvGal2, with four tandemly arrayed carbohydrate recognition domains (CRDs). Phylogentic analysis of the CvGal2 CRDs suggests close relationships with homologous CRDs from CvGal1. Glycan array analysis, however, revealed that, unlike CvGal1 which preferentially binds to the blood group A tetrasaccharide, CvGal2 recognizes both blood group A and B tetrasaccharides and related structures, suggesting that CvGal2 has broader binding specificity. Furthermore, SPR analysis demonstrated significant differences in the binding kinetics of CvGal1 and CvGal2, and structural modeling revealed substantial differences in their interactions with the oligosaccharide ligands. CvGal2 is homogeneously distributed in the hemocyte cytoplasm, is released to the extracellular space, and binds to the hemocyte surface. CvGal2 binds to P. marinus trophozoites in a dose-dependent and beta-galactoside specific manner. Strikingly, negligible binding of CvGal2 was observed for Perkinsus chesapeaki, a sympatric parasite species mostly prevalent in the clams Mya arenaria and Macoma balthica. The differential recognition of Perkinsus species by the oyster galectins is consistent with their relative prevalence in oyster and clam species and supports their role in facilitating parasite entry and infectivity in a host-preferential manner. PMID- 26158804 TI - Effect of the Conjugation Density of Triphenylphosphonium Cation on the Mitochondrial Targeting of Poly(amidoamine) Dendrimers. AB - Many clinically relevant diseases with known poor therapeutic outcomes, including cancer and neurodegenerative disorders, have been directly linked to mitochondrial dysfunction. The ability to efficiently target therapeutics to intracellular organelles such as mitochondria may represent new opportunities for the effective treatment of such ailments. The present study reports the synthesis, cellular uptake, cytotoxicity, and mitochondrial colocalization of conjugates of triphenylphosphonium cation (TPP) to amine-terminated, generation 4, poly(amidoamine) (PAMAM) dendrimer (G4NH2) nanocarriers. The mitochondrial targeting moiety TPP was either directly conjugated to G4NH2 (G4NH2-TPP) or to the dendrimer through a flexible polyethylene glycol (PEG) linker (G4NH2-PEGTPP). Conjugation was done at various TPP densities to assess their biological activity and potential for mitochondrial-targeted drug delivery. Tests in an in vitro model of the human alveolar carcinoma (A549 cells) showed that even at a low TPP density (~5 TPP) both the cellular internalization and mitochondrial targeting increase significantly, as determined by fluorescence activated cell sorting (FACS) and confocal microscopy (CM), respectively. At a density of ~10 TPP per G4NH2, further increase in cellular internalization and mitochondrial targeting was achieved. However, at this higher density, the nanocarriers also showed pronounced cytotoxicity. It was observed that the toxicity of the conjugates is decreased upon the addition of a PEG linker between the dendrimer and TPP (G4NH2 PEGTPP), while the mitochondrial targeting ability of the nanocarriers is not affected as the PEG density increases. The proposed strategies indicate that TPP conjugated G4NH2 dendrimers represent a potentially viable strategy for the targeting of therapeutic molecules to mitochondria, which may help improve therapeutic outcomes of diseases related to mitochondrial dysfunction. PMID- 26158806 TI - Close-Call Screening and Shared Decision Making. PMID- 26158807 TI - Utility of Physician Report Cards in Patient Referral. PMID- 26158805 TI - Patient-reported side effects, concerns and adherence to corticosteroid treatment for asthma, and comparison with physician estimates of side-effect prevalence: a UK-wide, cross-sectional study. AB - BACKGROUND: Non-adherence to corticosteroid treatment has been shown to reduce treatment efficacy, thus compromising asthma control. AIMS: To examine the experiences of treatment side effects, treatment concerns and adherence to inhaled (ICS) and oral corticosteroids (OCS) among people with asthma and to identify the degree of concordance between clinician estimates of side effects and the prevalence reported by patients. METHODS: Asthma UK members were sent validated questionnaires assessing treatment concerns, experiences of side effects and adherence. Questionnaires measuring clinicians' estimates of the prevalence of corticosteroid side effects were completed online. RESULTS: Completed questionnaires were returned by 1,524 people taking ICS, 233 taking OCS and 244 clinicians (67% of clinicians were primary care nurses). Among people with asthma, 64% of those taking ICS and 88% of those taking OCS reported ? 1 side effect. People reporting high adherence to ICS (t = -3.09, P<0.005) and those reporting low adherence to OCS (t = 1.86, P < 0.05; one-tailed test) reported more side effects. There was a disparity between clinicians' estimates of the frequency of side effects and the frequency reported by people with asthma: e.g., although 46% of people taking ICS reported sore throat, clinicians estimated that this figure would be 10%. Patients who reported side effects had stronger concerns about both ICS (r = 0.46, P < 0.0001) and OCS (r = 0.50, P < 0.0001). Concerns about corticosteroids were associated with low adherence to ICS (t = 6.90, P < 0.0001) and OCS (t = 1.71; P < 0.05; one-tailed test). CONCLUSIONS: An unexpectedly large proportion of people with asthma experienced side effects and had strong concerns about their treatment, which compromised adherence. These findings have implications for the design of interventions to optimise asthma control through improved adherence. PMID- 26158808 TI - Patient Satisfaction Reporting and Its Implications for Patient Care. PMID- 26158809 TI - 2013 Winning Essay: The Accountable Care Paradigm Shift: New Ethical Considerations. AB - The current state of our health care system is analogous to the status of science that Kuhn describes as "a proliferation of compelling articulations, the willingness to try anything, the expression of explicit discontent, the recourse to philosophy and to debate over fundamentals" [27]. ACOs represent a paradigm shift in the way health care is delivered. As with any dramatic public policy change, ethical issues will arise. These are surmountable challenges, and with open communication, physicians such as the Midstate group can partner effectively with hospital systems to ensure the delivery of quality, evidence-based care while at the same reorienting the culture to be attentive to its fiduciary responsibilities. PMID- 26158810 TI - Accountable Care Organizations: The First Two Years' Performance and Directions for the Future. PMID- 26158811 TI - Incentives for Physicians to Pursue Primary Care in the ACA Era. PMID- 26158812 TI - The Next Generation of Physician Report Cards. PMID- 26158813 TI - Comparative Effectiveness Research Would Contribute More to Ethical Policy Making if Cost Were Considered. PMID- 26158814 TI - Consumer Satisfaction with Health Insurance Coverage in Massachusetts. PMID- 26158815 TI - The Ethics of Expanding Health Coverage through the Private Market. PMID- 26158816 TI - The Distributional Effects of the Affordable Care Act's Cadillac Tax by Worker Income. PMID- 26158817 TI - What the ACA Should Have Included--Physician Perspectives at the University of Pennsylvania. PMID- 26158819 TI - Introduction to the Special Issue: Improving Psychological Science. PMID- 26158820 TI - Applying the Psychology of Science to the Science of Psychology: Can Psychologists Use Psychological Science to Enhance Psychology as a Science? AB - Added to the already tremendous diversity of subdisciplines of psychological science is the psychology of science. Although research on the psychology of science began in 1874, the field has seen a substantial expansion of activity in recent years. One particular subset of this research literature has special importance: namely, inquiries into the psychology of doing great science. These investigations may be assigned into four groups: cognitive, differential, developmental, and social. Each of these deal with critical questions that can, if answered, contribute directly to the improvement of psychology as a science. Potential applications include (a) the identification of scientific talent in psychology, (b) the education of future investigators in psychological science, and (c) the evaluation of psychology's progress as a scientific endeavor. PMID- 26158821 TI - We Have to Break Up. AB - Three mostly positive developments in academic psychology-the cognitive revolution, the virtual requirement for multiple study reports in our top journals, and the prioritization of mediational evidence in our data-have had the unintended effect of making field research on naturally occurring behavior less suited to publication in the leading outlets of the discipline. Two regrettable consequences have ensued. The first is a reduction in the willingness of researchers, especially those young investigators confronting hiring and promotion issues, to undertake such field work. The second is a reduction in the clarity with which nonacademic audiences (e.g., citizens and legislators) can see the relevance of academic psychology to their lives and self-interest, which has contributed to a concomitant reduction in the availability of federal funds for basic behavioral science. Suggestions are offered for countering this problem. PMID- 26158818 TI - Investigating impact of Vascular Endothelial Growth Factor Polymorphisms in Epithelial Ovarian Cancers: A Study in the Indian Population. AB - Epithelial ovarian cancer is one of the increasingly incident malignancies that is notorious because of its evasiveness for early diagnosis and high mortality rates. Epithelial ovarian cancers are highly dependent on pathologic vasculature and Vascular Endothelial Growth Factor is known to be one of the most efficient angiogenic factors. Polymorphisms of the VEGF gene, in this study, were assessed for association with the malignancy and other clinico-pathological factors. 300 case samples and 320 age and mensus status matched controls were inculcated into the study. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were the six single nucleotide polymorphisms that were scrutinized. Genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism. rs 3025039 showed immense promise as a marker for disease aggression and recurrence and a factor for poor prognosis. rs699947 showed least association with the disease and clinico-pathologic factors studied. rs833061, rs 1570360 showed significant association with some clinico-pathological factors such as bilateral affliction of ovaries and post operative CA-125 levels. rs2010963 associated with presence of ascites in higher volumes. The SNPs under consideration showed no formidable linkage in our study samples. A haplotype analysis (excluding rs699947 and rs1413711) revealed 5 frontrunners being present in >85% of the population with TGGC and CGCC associating significantly as protective and risk factors respectively. These haplotypes showed a dose dependent additive effect of their seeming functionality. This study is unique and a first of its kind carried out in the Indian population of South-east Asia. PMID- 26158822 TI - Minimally Sufficient Research. AB - Psychology would be improved if researchers stopped using complicated designs, procedures, and statistical analyses for the sole reason that they are able to do so. The present article reviews some of the classic studies in psychology, all of which are breathtakingly simple. The notion of minimally sufficient research is suggested as an ideal worth following. More generally, questions should dictate research methods and statistical analyses, not vice versa. PMID- 26158823 TI - What Are the Brain Mechanisms on Which Psychological Processes Are Based? AB - That the human brain is the organ of the mind is not in dispute, but we know remarkably little about the brain mechanisms underlying the mind. What are the functional structures and computational processes of the human brain that subserve cognition, emotion, and behavior? Given the complexity of the human brain, progress in understanding the functional organization and structure of the human brain depends on sophisticated theoretical specifications of the psychological representations and processes that differentiate two or more comparison conditions. Psychological scientists, therefore, are well positioned to lead the search for brain mechanisms underlying psychological processes. Doing so constitutes an expansion of the purview of psychological science beyond a science of behavior, and beyond a science of the mind, to include a science of the brain. Such an expansion of the mission of psychological science has implications for the infrastructure and training needs of the discipline. PMID- 26158824 TI - Why Can't We Be More Idiographic in Our Research? AB - Most psychological scientists make inferences about the relations among variables of interest by comparing aggregated data from groups of individuals. Although this method is unarguably a useful one that will continue to yield scientific advances, important limitations exist regarding the efficiency and flexibility of such designs, as well as with the generality of obtained results. Idiographic research strategies, which focus on the intensive study of individual organisms over time, offer a proficient and flexible alternative to group comparison designs; however, they are rarely taught in graduate training programs and are seldom used by psychological scientists. We highlight some of the unique strengths of idiographic methods, such as single case experimental designs, and suggest that psychological science will progress most efficiently with an increased use of such methods in both laboratory and clinical settings. PMID- 26158825 TI - Two Is Better Than One. AB - Psychologists too often rely on only one source of evidence to affirm the validity of a construct. However, they usually do not know all the conditions that can produce the evidence they gather. Hence, the inference is often limited to the data gathered and does not generalize to other categories of information. Examples of this habit are presented along with the suggestion that all social scientists should affirm the utility of their concepts with more than one class of information. PMID- 26158826 TI - It's Time We Brought Introspection Out of the Closet. AB - I identify the main reasons why introspection unofficially has been banned from the field for some 100 years, though it has been partly smuggled back in through the use of "verbal (self-) reports." I then show why introspection is indispensable to psychology. I argue that this ban has retarded the progress of psychology by taking attention away from the problem of the accuracy of self reports, limiting our understanding of concepts like emotion, discouraging psychologists from using introspection themselves, and ignoring the study of how to develop introspective skill. I conclude by suggesting some approaches to validating introspective reports. PMID- 26158827 TI - Evidence-Based Ethical Problem Solving (EBEPS). AB - Although there is usually agreement about the ethical principles that should govern human research, there may be little agreement on how those principles should be interpreted into research procedures in some instances. Empirical research on ethical issues can often elucidate ways to improve on existing research practices and resolve debates with one's institutional review board. PMID- 26158828 TI - Do IRBs Pass the Minimal Harm Test? AB - We describe examples of institutional review board (IRB) actions that have delayed or thwarted research that could not conceivably be considered to pose more than minimal risk to participants. We propose three changes to improve the IRB process and reduce both human and financial costs. PMID- 26158829 TI - What (and Where) Is the Ethical Code Concerning Researcher Conflict of Interest? AB - Decision makers are expected to identify and perhaps recuse themselves from actions that affect entities (such as relatives or corporations) to which their relationships create an appearance of conflict of interest. This article illustrates relationships that can create conflicts of interest for editors, grant decision makers, journal and grant reviewers, expert witnesses, and also for many researchers with method or theory commitments. The author urges psychology's professional associations to do what they now do either minimally or not at all: provide ethical guidelines that identify these conflicts and offer reasoned advice on managing them. PMID- 26158830 TI - Publishing in the Psychological Sciences: Enhancing Journal Impact While Decreasing Author Fatigue. AB - The publication process in the psychological sciences is unduly tedious and would benefit from the adoption of a publishing model typical of the neurosciences and basic sciences. The author argues that such a change would result in higher impact publications in the psychological sciences and would also conserve the time of busy scientists. PMID- 26158831 TI - Publishing in Scientific Journals: We're Not Just Talking to Ourselves Anymore. AB - Increasingly, psychological research is part of the integrative science that spans multiple disciplines, but variable publication standards undermine some of the integrative progress that might otherwise be made. Word limits for articles, norms for shorter reviews (which would improve turnaround time), electronic availability, and appropriate marketing of research will bring psychology closer to the central role it could play in integrative science. PMID- 26158832 TI - The Air We Breathe: A Critical Look at Practices and Alternatives in the Peer Review Process. AB - Anonymous peer review has served as the bedrock of research dissemination in scientific psychology for decades and has only sporadically been questioned. However, other disciplines, such as biomedicine and physics, have found the traditional peer-review system to be wanting and have begun to test and try alternative practices. In this article, we survey criticisms of the traditional peer-review system and describe several alternatives in the interests of facilitating discussion and debate. We also consider why the natural sciences tend to employ fewer reviewers and have lower rejection rates than do the social sciences. Our two recommendations are that a serious discussion of problems and alternatives to peer review should be started at all levels of psychology and that a science of research communication should be a priority, with psychologists as part of its advance guard because of their relevant substantive and methodological knowledge. PMID- 26158833 TI - The Psychology of Referencing in Psychology Journal Articles. AB - Citation statistics can affect major professional decisions, but little is known about how important a particular reference is to the citing document. We asked 49 psychologists to rate the importance of every reference in their own empirical paper and to indicate the primary citation reason. References cited for conceptual ideas or to justify methods and data analyses were regarded as more important than references cited for general background, limitations, or future research. The location, frequency, and length of a citation predicted its importance, but such relationships were weaker for self-citations. We make suggestions about referencing for authors, editors, and bibliographic database designers. PMID- 26158834 TI - The Peer-Review and Editorial System: Ways to Fix Something That Might Be Broken. AB - The present article focuses on ways to make the peer-review and editorial process more efficient and more equitable for authors. In particular, we focus on the role of editors and action editors in the process of selecting and managing reviewers, balancing their own impressions of the manuscript with the reviewers' feedback, and rendering a fair and equitable editorial decision. We advance several recommendations to conserve reviewer time, provide authors with appropriate recourse when their papers are rejected unfairly, and expedite the processing of manuscripts that do not meet the standards of the journal to which they have been submitted. PMID- 26158835 TI - Masked Reviews Are Not Fairer Reviews. AB - Many people believe that reviewers are less likely to produce unfair and biased reviews when they do not know the identity of the authors. However, there is surprisingly little evidence of such bias, there is little evidence that masked review is effective in addressing bias, and masked review has potential costs and drawbacks to the research community. More empirical work on the existence and nature of bias is needed. PMID- 26158836 TI - What If Social Scientists Had Reviewed Great Scientific Works of the Past? AB - One might question whether the great works in the history of science would get good reviews if subjected to the type of reviewing process to which psychologists are forced to submit their manuscripts. In some ways, behavioral scientists are too critical, and in other ways they are insufficiently so. To explore these issues, we imagine that great works from the history of nonsocial sciences were submitted for review in behavioral science journals and present simulated editor letters summarizing the comments of behavioral science reviewers. The philosophical underpinnings and justifications of the arguments are discussed, and recommendations for improved reviewing are offered. PMID- 26158837 TI - Are Social Scientists Harder on Their Colleagues Than Physical Scientists Were on Theirs in the Past? Commentary on Trafimow & Rice (2009). AB - Trafimow and Rice (2009; this issue) have written a thought-provoking article that addresses an important issue in a creative, informative, and engaging way. In a series of vignettes, the authors imagine how several of the better known developments of science might have fared if the manuscripts in which they were first described had been assessed according to the standards and predilections of current reviewers of manuscripts in the social sciences. In this commentary, I note points made by Trafimow and Rice with which I agree, mention some questions that the article raises that are important in my view, challenge the authors' assumption that contemporary social scientists generally treat the ideas of their colleagues more harshly than past physical scientists treated those of theirs, and express an opinion about the merits of the peer-review system as it currently functions in the social sciences. Although I acknowledge that the current system is far from perfect, I argue that it does a passably good job and question whether the reviews it produces are generally too harsh. PMID- 26158838 TI - Problems, Pitfalls, and Promise in the Peer-Review Process: Commentary on Trafimow & Rice (2009). AB - In their critique of the peer-review process, Trafimow and Rice (2009, this issue) dramatize a number of ways in which the review process can go awry. On the whole, I agree that the issues highlighted by the authors are indeed problems worthy of careful consideration. However, I fear that their treatment of these issues could send mixed and misleading messages to would-be reviewers about what constitutes proper reviewing behavior, in part because the authors had little to say on this topic. In the present commentary, I attempt to address this omission by discussing qualities of a good review and by distinguishing several responsibilities in the peer-review process that lie uniquely with the editor and the author. Finally, I identify three general strategies for improving the peer review process that center on providing better, more formalized training of reviewers; increasing accountability of both editors and reviewers; and reducing burden on the peerreview system. PMID- 26158839 TI - Learning for Life: An Ecological Approach to Pedagogical Research. AB - The trend to convert laboratory findings on the conditions associated with optimal memory into recommendations for teaching strategies and learning aids will harm students if findings fail to generalize to students' usual learning environments. Moreover, it is likely that pedagogies function differently for students with different degrees of background knowledge, time, and interest in the subject matter; that some support activities will prevent students from honing their ability learn from narrative material without guided learning; and that an overuse of learning aids will tax students' ability to use them effectively. We contrast two approaches to developing pedagogy-memory first and pedagogical ecology-and explain how the human factors approach of pedagogical ecology could be a more satisfying model for the scholarship of teaching and learning. PMID- 26158840 TI - Recapturing a Context for Psychology: The Role of History. AB - With the ever-increasing fragmentation of psychology into narrower subspecialties, the field devolves further and further into a focus on specialized knowledge, answering smaller questions and avoiding the larger and more meaningful ones. It is argued that specialized knowledge acquires its meaning only from an understanding of its place in a broader intellectual context. Psychology appears to have lost that context and perhaps the opportunity for a more significant role in modern science. An understanding of the history of psychological science offers a way to recapture that context and to prepare future psychologists to address the truly significant behavioral problems that face our world. PMID- 26158841 TI - Using New Interactive Media to Enhance the Teaching of Psychology (and Other Disciplines) in Developing Countries. AB - My idea for improving psychology responds to the challenge of teaching psychology in lower income, developing countries. With new Web-based e-books on the horizon, I suggest harnessing the Internet to deliver state-of-the-art, interactive, low cost, locally adapted content to students who cannot afford books. PMID- 26158842 TI - Solving Social Problems Like a Psychologist. AB - We suggest that psychologists can play a larger role in the solution of important social problems. Psychology brings two important qualities to the study of social problems: attention to psychological process and rigorous methodology. Our key task is to define social problems in part as psychological problems, and to conduct rigorous research that tests novel psychological solutions. Examples of research that has taken this path-research on race differences in academic performance, on the training of executive function and intelligence, and on the provision of socially constructive default decisions-are provided. We argue that addressing social problems can enrich our science by connecting psychologists to interdisciplinary teams and by providing contexts in which to demonstrate, in striking ways, the value of a psychological approach. PMID- 26158843 TI - Impact of Racism on Ethnic Minority Mental Health. AB - A problem in ethnic minority mental health that can be solved in the foreseeable future is understanding how subtle and covert forms of racism affect psychological health of racial minorities. Although scientific psychology has generated a large body of literature on racial prejudice, stereotypes, intergroup attitudes, and racial bias and their often implicit and automatic nature, relatively little is known about the effects of these subtle racial bias on minority individuals. Following a selective review of recent developments in experimental psychology and multicultural psychology, I suggest some promising approaches and opportunities for future integration that would advance the field. PMID- 26158844 TI - A New Approach to Reducing Disorder and Improving Well-Being. AB - Psychological science has usually approached the treatment of disorder through research on individual combinations of risk and protective factors (including life experiences, thinking styles, behaviors, social relationships and genes) and the application of interventions that focus on improvements in the individual. However, we can do better than this. Not only should we be aiming to enhance well being rather than merely reducing disorder, but we should also be doing so for the majority of people rather than the few who have a disorder. In this article, I focus on the mental health spectrum and make the case for a broad population based approach. I argue that a very small shift in the population mean of the underlying symptoms or risk factors can do more to enhance well-being and reduce disorder than would any amount of intervention with individuals who need help. Examples from research on alcohol abuse and psychological distress are presented to illustrate the value of a population-based approach. PMID- 26158845 TI - The Diagnostic Accuracy of the M2 Pyruvate Kinase Quick Stool Test--A Rapid Office Based Assay Test for the Detection of Colorectal Cancer. AB - BACKGROUND: M2 pyruvate kinase (M2PK) is an oncoprotein secreted by colorectal cancers in stools. This the first report on the accuracy of a rapid stool test in the detection of colorectal cancer (CRC). OBJECTIVE: To determine the sensitivity, specificity and positive and negative predictive value of a rapid, point of care stool test M2 PK- the M2PK Quick. METHODS: Consecutive cases of endoscopically diagnosed and histological proven CRC were recruited. Stools were collected by patients and tested with the immunochromatographic M2PK Quick Test (Schebo Biotech AC, Giessen, Germany). Controls were consecutively chosen from patients without any significant colorectal or gastrointestinal disease undergoing colonoscopy. CRC was staged according to the AJCC staging manual (7th Edition) and location of tumor defined as proximal or distal. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy were: 93%, 97.5%, 94.9%, 96.5% and 96.0% respectively. The positive predictive value for proximal tumors was significantly lower compared to distal tumors. No differences were seen between the different stages of the tumor. CONCLUSIONS: The M2-PK Quick, rapid, point-of-care test is a highly accurate test in the detection of CRC. It is easy and convenient to perform and a useful diagnostic test for the detection of CRC in a clinical practice setting. PMID- 26158846 TI - What Is a Mild Winter? Regional Differences in Within-Species Responses to Climate Change. AB - Climate change is known to affect ecosystems globally, but our knowledge of its impact on large and widespread mammals, and possibly population-specific responses is still sparse. We investigated large-scale and long-term effects of climate change on local population dynamics using the wild boar (Sus scrofa L.) as a model species. Our results show that population increases across Europe are strongly associated with increasingly mild winters, yet with region-specific threshold temperatures for the onset of exponential growth. Additionally, we found that abundant availability of critical food resources, e.g. beech nuts, can outweigh the negative effects of cold winters on population growth of wild boar. Availability of beech nuts is highly variable and highest in years of beech mast which increased in frequency since 1980, according to our data. We conclude that climate change drives population growth of wild boar directly by relaxing the negative effect of cold winters on survival and reproduction, and indirectly by increasing food availability. However, region-specific responses need to be considered in order to fully understand a species' demographic response to climate change. PMID- 26158847 TI - Minimal Inter-Fractional Fiducial Migration during Image-Guided Lung Stereotactic Body Radiotherapy Using SuperLock Nitinol Coil Fiducial Markers. AB - OBJECTIVES: Stereotactic body radiotherapy (SBRT) is being increasingly used for the treatment of patients with lung cancer or lung metastasis who are medically unfit to undergo resection. In order to improve accuracy and confidence in targeting tumors, many centers rely on fiducial implantation. We evaluated the migration of a novel fiducial marker specifically designed for lung tissue implanted via electromagnetic navigation bronchoscopy (ENB). METHODS: We retrospectively quantified the individual and group migrations of SuperLock nitinol coil fiducials for 15 patients receiving lung stereotactic body radiotherapy (SBRT), in order to evaluate the reliability of using these fiducials as a target surrogate for cases where tumors cannot be clearly delineated on cone beam CTs (CBCTs). For each fraction, we compared the individual and group migrations of the fiducials between the planning CT and the acquired CBCT. The group migration was defined as the distance between the centroids of the fiducial group and GTV. RESULTS: A total of 16 lung targets were included in our study for these 15 patients (one patient with two targets). Of 55 fiducials placed, we observed a 100% retention rate. The mean individual migration was 1.87 mm (range, 0.63-5.25 mm) with a standard deviation of 1.26 mm. The mean group migration was 1.94 mm (range, 0.03-6.19 mm) with a standard deviation of 1.45 mm. Overall, there was minimal change in the relative locations of the markers with respect to each other, as well as to the target. CONCLUSIONS: We found that the SuperLock nitinol coil fiducial marker positions are stable throughout the radiation treatment, and can be used as a reliable surrogate to target, and to avoid geometric misses during gated treatments. PMID- 26158848 TI - Reactions of Superoxide with Iron Porphyrins in the Bulk and the Near-Surface Region of Ionic Liquids. AB - The redox reaction of superoxide (KO2) with highly charged iron porphyrins (Fe(P4+), Fe(P8+), and Fe(P8-)) has been investigated in the ionic liquids (IL) [EMIM][Tf2N] (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and [EMIM][B(CN)4] (1-ethyl-3-methylimidazolium tetracyanoborate) by using time resolved UV/vis stopped-flow, electrochemistry, cryospray mass spectrometry, EPR, and XPS measurements. Stable KO2 solutions in [EMIM][Tf2N] can be prepared up to a 15 mM concentration and are characterized by a signal in EPR spectrum at g = 2.0039 and by the 1215 cm(-1) stretching vibration in the resonance Raman spectrum. While the negatively charged iron porphyrin Fe(P8-) does not react with superoxide in IL, Fe(P4+) and Fe(P8+) do react in a two-step process (first a reduction of the Fe(III) to the Fe(II) form, followed by the binding of superoxide to Fe(II)). In the reaction with KO2, Fe(P4+) and Fe(P8+) show similar rate constants (e.g., in the case of Fe(P4+): k1 = 18.6 +/- 0.5 M(-1) s(-1) for the first reaction step, and k2 = 2.8 +/- 0.1 M(-1) s(-1) for the second reaction step). Notably, these rate constants are four to five orders of magnitude lower in [EMIM][Tf2N] than in conventional solvents such as DMSO. The influence of the ionic liquid is also apparent during electrochemical experiments, where the redox potentials for the corresponding Fe(III)/Fe(II) couples are much more negative in [EMIM][Tf2N] than in DMSO. This modified redox and kinetic behavior of the positively charged iron porphyrins results from their interactions with the anions of the ionic liquid, while the nucleophilicity of the superoxide is reduced by its interactions with the cations of the ionic liquid. A negligible vapor pressure of [EMIM][B(CN)4] and a sufficient enrichment of Fe(P8+) in a close proximity to the surface enabled XPS measurements as a case study for monitoring direct changes in the electronic structure of the metal centers during redox processes in solution and at liquid/solid interfaces. PMID- 26158849 TI - Rapid neodymium release to marine waters from lithogenic sediments in the Amazon estuary. AB - Rare earth element (REE) concentrations and neodymium isotopic composition (ENd) are tracers for ocean circulation and biogeochemistry. Although models suggest that REE release from lithogenic sediment in river discharge may dominate all other REE inputs to the oceans, the occurrence, mechanisms and magnitude of such a source are still debated. Here we present the first simultaneous observations of dissolved (<0.45 MUm), colloidal and particulate REE and ENd in the Amazon estuary. A sharp drop in dissolved REE in the low-salinity zone is driven by coagulation of colloidal matter. At mid-salinities, total dissolved REE levels slightly increase, while ENd values are shifted from the dissolved Nd river endmember (-8.9) to values typical of river suspended matter (-10.6). Combining a Nd isotope mass balance with apparent radium isotope ages of estuarine waters suggests a rapid (3 weeks) and globally significant Nd release by dissolution of lithogenic suspended sediments. PMID- 26158851 TI - A Computational Model of a Descending Mechanosensory Pathway Involved in Active Tactile Sensing. AB - Many animals, including humans, rely on active tactile sensing to explore the environment and negotiate obstacles, especially in the dark. Here, we model a descending neural pathway that mediates short-latency proprioceptive information from a tactile sensor on the head to thoracic neural networks. We studied the nocturnal stick insect Carausius morosus, a model organism for the study of adaptive locomotion, including tactually mediated reaching movements. Like mammals, insects need to move their tactile sensors for probing the environment. Cues about sensor position and motion are therefore crucial for the spatial localization of tactile contacts and the coordination of fast, adaptive motor responses. Our model explains how proprioceptive information about motion and position of the antennae, the main tactile sensors in insects, can be encoded by a single type of mechanosensory afferents. Moreover, it explains how this information is integrated and mediated to thoracic neural networks by a diverse population of descending interneurons (DINs). First, we quantified responses of a DIN population to changes in antennal position, motion and direction of movement. Using principal component (PC) analysis, we find that only two PCs account for a large fraction of the variance in the DIN response properties. We call the two dimensional space spanned by these PCs 'coding-space' because it captures essential features of the entire DIN population. Second, we model the mechanoreceptive input elements of this descending pathway, a population of proprioceptive mechanosensory hairs monitoring deflection of the antennal joints. Finally, we propose a computational framework that can model the response properties of all important DIN types, using the hair field model as its only input. This DIN model is validated by comparison of tuning characteristics, and by mapping the modelled neurons into the two-dimensional coding-space of the real DIN population. This reveals the versatility of the framework for modelling a complete descending neural pathway. PMID- 26158850 TI - Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation. AB - The neonatal intestine is a very complex and dynamic organ that must rapidly adapt and remodel in response to a barrage of environmental stimuli during the first few postnatal weeks. Recent studies demonstrate that the zinc finger transcriptional repressor Blimp1/Prdm1 plays an essential role governing postnatal reprogramming of intestinal enterocytes during this period. Functional loss results in global changes in gene expression patterns, particularly in genes associated with metabolic function. Here we engineered a knock-in allele expressing an eGFP-tagged fusion protein under control of the endogenous regulatory elements and performed genome wide ChIP-seq analysis to identify direct Blimp1 targets and further elucidate the function of Blimp1 in intestinal development. Comparison with published human and mouse datasets revealed a highly conserved core set of genes including interferon-inducible promoters. Here we show that the interferon-inducible transcriptional activator Irf1 is constitutively expressed throughout fetal and postnatal intestinal epithelium development. ChIP-seq demonstrates closely overlapping Blimp1 and Irf1 peaks at key components of the MHC class I pathway in fetal enterocytes. The onset of MHC class I expression coincides with down-regulated Blimp1 expression during the suckling to weaning transition. Collectively, these experiments strongly suggest that in addition to regulating the enterocyte metabolic switch, Blimp1 functions as a gatekeeper in opposition to Irf1 to prevent premature activation of the MHC class I pathway in villus epithelium to maintain tolerance in the neonatal intestine. PMID- 26158852 TI - Identification of a Novel Agonist-Like Autoantibody in Preeclamptic Patients. AB - BACKGROUND: Recent studies have shown that preeclampsia (PE) is associated with the presence of autoantibodies (AABs) that activate the angiotensin II AT1 receptor, which could contribute to many of the symptoms of PE. METHODS: To investigate the frequency and the targets of AABs in preeclamptic women (31 cases) and healthy pregnant normotensive women (29 cases) in Brazil, antibodies from serum samples were detected by a bioassay using spontaneously beating neonatal rat cardiomyocytes in culture. In the cardiomyocytes, the agonistic AABs induce a positive or negative chronotropic response, mimicking the corresponding receptor agonists. The specificity of the AAB response was identified by specific receptor antagonists. RESULTS: Thirty preeclamptic patients (97%) presented AABs against the angiotensin II AT1 receptor. The agonistic effect of the AAB was blocked by irbesartan and neutralized by a peptide corresponding to the second extracellular loop of this receptor. Strikingly, we discovered that all sera from the severe preeclamptic patients (16 cases) contained a novel agonist-like AAB directed against the endothelin-1 ETA receptor in addition to the AABs against the angiotensin II AT1 receptor. This AAB was selectively blocked by the antagonist BQ-123, antagonized by the protein kinase C (PKC) inhibitor Calphostin C and neutralized by peptides corresponding to the second extracellular loop of the endothelin-1 ETA receptor subtype. CONCLUSIONS: We described, for the first time, the presence of endothelin-1 ETA receptor AABs in PE. Our results suggest that the presence of both agonistic AABs may be involved in the pathogenesis of severe PE. PMID- 26158853 TI - Comparison of 4 Admission Blood Pressure Indexes for Predicting 30-Day Mortality in Patients With ST-Segment Elevation Myocardial Infarction. AB - BACKGROUND: We compared admission systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting 30-day all-cause mortality in patients with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock. METHODS: A retrospective study was performed in 7,033 consecutive STEMI patients. Multivariate-adjusted hazard ratios (HRs) with a 10mm Hg increment and quartiles of each blood pressure were determined by Cox proportional hazard analyses; Wald chi (2) tests were used to compare the strength of relationships. RESULTS: Totally 593 (8.4%) patients died during follow-up. Of 4 indexes, only SBP (HR 0.94 per 10mm Hg, 95% confidence interval (CI) 0.91 to 0.98; P = 0.001) and PP (HR 0.89 per 10 mmHg, 95% CI 0.85 to 0.94; P < 0.001) were significantly associated with 30-day all cause mortality; these in the highest vs. lowest quartiles of SBP (>=140 vs. <110mm Hg) and PP (>=60 vs. <40mm Hg) had HRs of mortality of 0.70 (95% CI 0.55 to 0.87; P = 0.003) and 0.60 (95% CI 0.47 to 0.75; P < 0.001), respectively. Compared with SBP, PP was a better predictor for mortality no matter in men (chi (2) = 5.9 for per 10mm Hg, chi (2) = 10.8 for quartiles) or women (chi (2) = 15.1 for per 10mm Hg, chi (2) = 19.5 for quartiles), and the relationship remained significant after adjustment of SBP. There was a pattern of declining risk with increasing blood pressures for mortality, and this trend was mainly observed in age groups of more than 70 years. CONCLUSIONS: Pulse pressure was an independent predictor of mortality in patients with STEMI, and low admission blood pressure should serve as a warning sign. PMID- 26158854 TI - Trends in Elevated Blood Pressure Among US Children and Adolescents: 1999-2012. AB - BACKGROUND: The prevalence of elevated blood pressure (BP) has been reported to increase significantly among the US children and adolescents from 1988-1994 to 1999-2008. We aimed to examine the recent trends in BP levels and prevalence of elevated BP, as well as related influencing factors among US children and adolescents. METHODS: Data of National Health and Nutrition Examination Survey (NHANES) 1999-2012 were combined into 3 time periods (1999-2002, 2003-2008, and 2009-2012) for the analysis. A total of 14,270 US children and adolescents aged 8 17 years were included in the current analysis. The sex-, age-, and height-BP standards recommended by the US Fourth Report were used to define high BP and elevated BP (including pre-HBP and HBP). RESULTS: Mean systolic BP (SBP) and diastolic BP (DBP) decreased by 0.7 and 4.2mm Hg from 1999-2002 to 2009-2012, respectively. In 2009-2012, the prevalence of elevated BP and HBP in children and adolescents were 9.6% and 1.6%, with the absolute reduction of 2.8% and 1.3% from 1999-2002 to 2009-2012, respectively. In addition, daily intakes of total energy, carbohydrate, total saturated fatty acids, and caffeine decreased during the period between 1999-2002 and 2009-2012 (all P < 0.05), whereas daily intake of total polyunsaturated fatty acids and dietary fiber increased (P < 0.05). CONCLUSIONS: Mean BP levels as well as the prevalence of elevated BP and HBP among US children and adolescents have declined during the past decade. In addition, there might be an associated change in dietary factors. PMID- 26158856 TI - The Science of Eyewitness Testimony Has Come of Age. PMID- 26158855 TI - Eyewitness Evidence: Improving Its Probative Value. AB - The criminal justice system relies heavily on eyewitnesses to determine the facts surrounding criminal events. Eyewitnesses may identify culprits, recall conversations, or remember other details. An eyewitness who has no motive to lie is a powerful form of evidence for jurors, especially if the eyewitness appears to be highly confident about his or her recollection. In the absence of definitive proof to the contrary, the eyewitness's account is generally accepted by police, prosecutors, judges, and juries. However, the faith the legal system places in eyewitnesses has been shaken recently by the advent of forensic DNA testing. Given the right set of circumstances, forensic DNA testing can prove that a person who was convicted of a crime is, in fact, innocent. Analyses of DNA exoneration cases since 1992 reveal that mistaken eyewitness identification was involved in the vast majority of these convictions, accounting for more convictions of innocent people than all other factors combined. We review the latest figures on these DNA exonerations and explain why these cases can only be a small fraction of the mistaken identifications that are occurring. Decades before the advent of forensic DNA testing, psychologists were questioning the validity of eyewitness reports. Hugo Munsterberg's writings in the early part of the 20th century made a strong case for the involvement of psychological science in helping the legal system understand the vagaries of eyewitness testimony. But it was not until the mid- to late 1970s that psychologists began to conduct programmatic experiments aimed at understanding the extent of error and the variables that govern error when eyewitnesses give accounts of crimes they have witnessed. Many of the experiments conducted in the late 1970s and throughout the 1980s resulted in articles by psychologists that contained strong warnings to the legal system that eyewitness evidence was being overvalued by the justice system in the sense that its impact on triers of fact (e.g., juries) exceeded its probative (legal-proof) value. Another message of the research was that the validity of eyewitness reports depends a great deal on the procedures that are used to obtain those reports and that the legal system was not using the best procedures. Although defense attorneys seized on this nascent research as a tool for the defense, it was largely ignored or ridiculed by prosecutors, judges, and police until the mid 1990s, when forensic DNA testing began to uncover cases of convictions of innocent persons on the basis of mistaken eyewitness accounts. Recently, a number of jurisdictions in the United States have implemented procedural reforms based on psychological research, but psychological science has yet to have its fullest possible influence on how the justice system collects and interprets eyewitness evidence. The psychological processes leading to eyewitness error represent a confluence of memory and social-influence variables that interact in complex ways. These processes lend themselves to study using experimental methods. Psychological science is in a strong position to help the criminal justice system understand eyewitness accounts of criminal events and improve their accuracy. A subset of the variables that affect eyewitness accuracy fall into what researchers call system variables, which are variables that the criminal justice system has control over, such as how eyewitnesses are instructed before they view a lineup and methods of interviewing eyewitnesses. We review a number of system variables and describe how psychological scientists have translated them into procedures that can improve the probative value of eyewitness accounts. We also review estimator variables, variables that affect eyewitness accuracy but over which the system has no control, such as cross-race versus within-race identifications. We describe some concerns regarding external validity and generalization that naturally arise when moving from the laboratory to the real world. These include issues of base rates, multicollinearity, selection effects, subject populations, and psychological realism. For each of these concerns, we briefly note ways in which both theory and field data help make the case for generalization. PMID- 26158857 TI - Indoor Particulate Matter < 2.5 MUm in Mean Aerodynamic Diameter and Carbon Monoxide Levels During the Burning of Mosquito Coils and Their Association With Respiratory Health. AB - BACKGROUND: An estimated 700 million people suffer from mosquito-borne diseases worldwide. Various types of mosquito repellents are widely used to prevent mosquito bites. The objectives of this study were (1) to measure the indoor levels of particulate matter < 2.5 MUm in mean aerodynamic diameter (PM2.5) and carbon monoxide (CO) during the burning of mosquito coils (MCs) and study the impact of indoor ventilation patterns; and (2) to study and compare the prevalence of respiratory ailments in homes using different types of mosquito repellents. METHODS: Indoor PM2.5 and CO levels were measured inside a bedroom during the burning of MCs keeping the window and/or door open/closed over a 6-h duration. A cross-sectional survey was conducted in three villages where 465 individuals were administered a questionnaire that captured demographic details, type and duration of mosquito repellents used, and prevalence of respiratory symptoms and diseases. RESULTS: Fifty-three percent of the subjects burned MCs on most days of the week, and 63% did so with their doors and windows closed. Burning of MCs produced very high levels of PM2.5 (1,031 MUg/m(3) mean, 1,613 MUg/m(3) peak) and CO (6.50 parts per million (ppm) mean, 10.27 ppm peak) when both the door and window were closed. These levels reduced by around 50% when the window was opened and > 95% when both the window and the door were opened. The prevalence rates of respiratory symptoms and diseases were higher in subjects using MCs, although not statistically significant. Those living in smaller homes and using MCs had significantly greater morbidity. CONCLUSIONS: Burning of MCs produces indoor levels of PM2.5 and CO that are higher than those reported during the burning of biomass fuels for cooking purposes and may be associated with respiratory morbidity. PMID- 26158858 TI - Ligand-responsive RNA mechanical switches. AB - Ligand-responsive RNA mechanical switches represent a new class of simple switching modules that adopt well-defined ligand-free and bound conformational states, distinguishing them from metabolite-sensing riboswitches. Initially discovered in the internal ribosome entry site (IRES) of hepatitis C virus (HCV), these RNA switch motifs were found in the genome of diverse other viruses. Although large variations are seen in sequence and local secondary structure of the switches, their function in viral translation initiation that requires selective ligand recognition is conserved. We recently determined the crystal structure of an RNA switch from Seneca Valley virus (SVV) which is able to functionally replace the switch of HCV. The switches from both viruses recognize identical cognate ligands despite their sequence dissimilarity. Here, we describe the discovery of 7 new switches in addition to the previously established 5 examples. We highlight structural and functional features unique to this class of ligand-responsive RNA mechanical switches and discuss implications for therapeutic development and the construction of RNA nanostructures. PMID- 26158859 TI - Cystophloroketals A-E, Unusual Phloroglucinol-Meroterpenoid Hybrids from the Brown Alga Cystoseira tamariscifolia. AB - Cystophloroketals A-E (1-5), five new phloroglucinol-meroditerpenoid hybrids, have been isolated together with their putative biosynthetic precursor, the monocyclic meroditerpenoid 6, from the Mediterranean brown alga Cystoseira tamariscifolia. They represent the first examples of meroditerpenoids linked to a phloroglucinol through a 2,7-dioxabicyclo[3.2.1]octane moiety. The chemical structures, including absolute configurations, were elucidated on the basis of extensive spectroscopic analysis (HR-ESIMS, 1D and 2D NMR, and ECD) and TDDFT ECD calculations. Compounds 1-6 were tested for their antifouling activity against several marine colonizing species (bacteria, fungi, invertebrates, micro- and macroalgae). Compound 6 showed high potency for the inhibition of macrofoulers (invertebrates and macroalgae), while cystophloroketals B (2) and D (4) displayed strong inhibition of the germination of the two macroalgae tested and moderate antimicrobial activities (bacteria, microalgae, and fungi). PMID- 26158860 TI - CpG oligodeoxynucleotide CpG-685 upregulates functional interleukin-21 receptor on chronic lymphocytic leukemia B cells through an NF-kappaB mediated pathway. AB - CpG oligodeoxynucleotides (ODNs) upregulate the interleukin-21 receptor (IL21R) and enhance IL-21-mediated cytotoxicity in chronic lymphocytic leukemia (CLL) B cells. We demonstrate that treatment of CLL B cells with the ODN CpG-685 leads to increased IL21R expression, and that this increased expression enhances the effects of IL-21 treatment as evidenced by increased phosphorylation of JAK1, STAT1, and STAT3, as compared to IL-21 treatment without prior CpG stimulation. Induction of IL21R by CpG-685 also enhanced IL-21-mediated cytotoxicity. The mechanism by which CpG ODNs upregulate IL21R has not been elucidated, although IL21R regulation in T cells has been shown to be linked to T cell receptor induced Sp1 binding to the IL21R promoter. Here, we demonstrate that luciferase reporter constructs containing the Sp1 binding site have increased basal luciferase activity compared to constructs lacking the Sp1 binding site, but fail to increase luciferase activity with CpG-685 stimulation in CLL B cells. By treating CLL cells with an NF-kappaB inhibitor, we inhibit the CpG ODN-mediated induction of IL21R, thus demonstrating that CpG-685 upregulates IL21R through an NF-kappaB mediated pathway. These findings suggest an alternative mechanism for induction of IL-21 receptor in CLL B cells and provide a basis for creation of future combination therapies. PMID- 26158862 TI - Attenuated mutant strain of Salmonella Typhimurium lacking the ZnuABC transporter contrasts tumor growth promoting anti-cancer immune response. AB - Salmonella Typhimurium has been shown to be highly effective as antitumor agent. The aim of this study was to investigate the tumor targeting efficacy and the mechanism of action of a specific attenuated mutant strain of Salmonella Typhimurium (STM) devoid of the whole operon coding for the high-affinity zinc transporter ZnuABC, which is required for bacterial growth in environments poor in zinc and for conferring full virulence to different Gram-negative pathogens.We showed that STM is able to penetrate and replicate into tumor cells in in vitro and in vivo models. The subcutaneous administration of STM in mammary adenocarcinoma mouse model led to both reduction of tumor growth and increase in life expectancy of STM treated mice. Moreover, investigating the potential mechanism behind the favorable clinical outcomes, we provide evidence that STM stimulates a potent inflammatory response and a specific immune pattern, recruiting a large number of innate and adaptive immune cells capable to contrast the immunosuppressive environment generated by tumors. PMID- 26158861 TI - Selective impact of CDK4/6 suppression on patient-derived models of pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in 14 of the 15 explants. In the single resistant explant, we identified the rare loss of the RB tumor suppressor as the basis for resistance. Patient-derived xenografts (PDXs) were developed in parallel, and unlike the xenografts emerging from established cell lines, the PDXs maintained the histoarchitecture of the primary tumor. These PDXs were highly sensitive to CDK4/6 inhibition, yielding a complete suppression of PDA proliferation. Together, these data indicate that primary PDA is sensitive to CDK4/6 inhibition, that specific biomarkers can delineate intrinsic resistance, and that established cell line models may not represent an adequate means for evaluating therapeutic sensitivities. PMID- 26158863 TI - Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1'-S-1'-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors. AB - PURPOSE: Previous in vitro and in vivo studies have reported that 1'-S-1' acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis mediated cell death in tumour cells via dysregulation of the NF-kappaB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA. EXPERIMENTAL DESIGN: To study the synergistic effect of both agents on human cancer xenografts, athymic nude (Nu/Nu) mice were used and treated with various combination regimes intraperitoneally. Serum levels of tumour markers for carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) were assessed using sandwich ELISA. IHC and Western blotting were also conducted on in vivo tumour biopsies to investigate the involvement of NF-kappaB regulated genes and inflammatory biomarkers. Quantification and correlation between drug efficacies and AFP-receptors were done using IF-IC and Pearson's correlation analysis. RESULTS: Mice exposed to combined treatments displayed higher reductions in tumour volume compared to stand alone agents, consistent with in vitro cytotoxicity assays. Milder signs of systemic toxicity, such as loss in body weight and inflammation of vital organs were also demonstrated compared to stand alone treatments. Tumour marker levels were consistent within all rhAFP/ACA treatment groups where levels of CEA and PSA were initially elevated upon commencement of treatment, and consecutively reduced corresponding to a decrease in tumour bulk volume. Both IHC and Western blotting results indicated that the combined action of rhAFP/ACA was not only able to down-regulate NF-kappaB activation, but also reduce the expression of NF-kappaB regulated genes and inflammatory biomarkers. The efficacy of rhAFP/ACA complex was also found to be weakly negatively correlated to the level of surface AFP-receptors between tumour types. CONCLUSIONS: This drug complex formulation shows great therapeutic potential against AFP-receptor positive tumours, and serves as a basis to overcome insoluble and non-specific anti-neoplastic molecules. PMID- 26158864 TI - SNP interactions of Helicobacter pylori-related host genes PGC, PTPN11, IL1B, and TLR4 in susceptibility to gastric carcinogenesis. AB - A series of host genes that respond to Helicobacter pylori (H. pylori) infection are involved in the process of gastric carcinogenesis. This study sought to examine interactions among polymorphisms of H. pylori-related genes PGC, PTPN11, TLR4, and IL1B and assess whether their interaction effects were modified by H. pylori infection. Thirteen polymorphisms of the aforementioned genes were genotyped by the Sequenom MassARRAY platform in 714 gastric cancer patients, 907 atrophic gastritis cases and 1276 healthy control subjects. When we considered the host genetic effects alone, gene-gene interactions consistently decreased the risks of gastric cancer and/or atrophic gastritis, including three two-way interactions: PGC rs6912200-PTPN11 rs12229892, PGC rs4711690-IL1B rs1143623 and PTPN11 rs12229892-IL1B rs1143623 and a three-way interaction: PGC rs4711690-PGC rs6912200-PTPN11 rs12229892. When the effect modification of H. pylori infection was evaluated, the cumulative effects of the aforementioned three-way interaction on atrophic gastritis susceptibility switched from being beneficial to being risky by the status of H. pylori infection. These data showed that SNP interactions among H. pylori-related genes PGC, PTPN11, and IL1B, are associated with susceptibility to gastric carcinogenesis. Moreover, we provided important hints of an effect modification by H. pylori infection on the cumulative effect of PGC and PTPN11 polymorphisms. Functional experiments and further independent large-scale studies especially in other ethnic populations are still needed to confirm our results. PMID- 26158866 TI - Removal of Heavy Metal Ions Using a Functionalized Single-Walled Carbon Nanotube: A Molecular Dynamics Study. AB - The adsorption behaviors of heavy metal ions Cd(2+), Cu(2+), Pb(2+), and Hg(2+), in aqueous media using functionalized single-walled carbon nanotube (SWCNT) with functional groups -COO(-), -OH, and -CONH2 are studied using molecular dynamics (MD) simulations. The results show that adsorption capacity is improved significantly using surface modification of SWCNT with carboxyl, hydroxyl, and amide functional groups. In addition, the adsorption capacity is found to increase with increasing metal-ion concentration. It is observed that the CNT COO(-) surface effectively adsorbs over 150-230% more metal ions than the bare CNT surface. On the contrary, -OH and -CONH2 are relatively weak functional groups where excess metal-ion adsorption compared to the bare CNT is in the range 10-47%. The structural properties, self-diffusion coefficients, and adsorption isotherms of the metal ions are computed and analyzed in detail. Moreover, the potential of mean force (PMF) is computed to understand the free energy of metal ions, in the presence of functional groups, which is remarkly higher in absolute terms, leading to significant affinity for adsorption compared to the case for the bare CNT. In general, the following order of adsorption of the metal ions on functionalized CNT is observed: Pb(2+) > Cu(2+) > Cd(2+) > Hg(2+). PMID- 26158865 TI - Interleukin-33 promotes inflammatory cytokine production in chronic airway inflammation. AB - Interleukin (IL)-33, belonging to the IL-1 family, is a novel cytokine that plays an important role in several chronic inflammatory diseases. Its role in chronic airway inflammation that develops into COPD is widely unknown. To determine this, we identified the expression of IL-33 in human bronchial epithelial layer and detected the inflammatory effects of IL-33 stimulation and the relative signaling pathways in human bronchial epithelial (HBE) cells and peripheral blood mononuclear cells (PBMCs), respectively. In this study, the expression of IL-33 in human bronchial epithelial layer was upregulated in COPD patients compared with normal controls. The expressions of IL-6 and IL-8 were also increased in both HBE cells and PBMCs, stimulated by IL-33 alone or combining the cigarette smoke extract (CSE). And the increased expressions could be partially blocked by ST2-Fc and IL-1RacP-Fc in both HBE cells and PBMCs. The p42/p44 ERK inhibitor in HBE cells and the p38 MAPK inhibitor in PBMCs exerted similar effects. Our data showed that IL-33 could induce and enhance the expression of IL-6 and IL-8 in HBE cells and PBMCs of COPD patients via ST2/IL-1RacP pathway and MAPKs pathway. Thus, the IL-33 is a promoter of chronic airway inflammation that contributes to COPD development. PMID- 26158867 TI - Rh-Catalyzed Domino Addition-Enolate Arylation: Generation of 3-Substituted Oxindoles via a Rh(lll) Intermediate. AB - A Rh-catalyzed domino conjugate addition-arylation sequence via a Rh(III) intermediate is reported. This process involving a proposed intramolecular oxidative addition of a rhodium enolate was utilized to achieve the synthesis of 3-substituted oxindole derivatives in moderate to excellent yields. PMID- 26158868 TI - Effect of Endotracheal Tube Size on Vocal Outcomes After Thyroidectomy: A Randomized Clinical Trial. AB - IMPORTANCE: The optimum size of endotracheal tube (ETT) for general anesthesia remains unresolved. Choice of ETT size may be of particular relevance to thyroid surgery because of the increased risk of laryngeal trauma and concerns regarding postoperative vocal outcomes. OBJECTIVE: To test our hypothesis that intubation with a smaller ETT would lead to reduced postoperative vocal impairment and associated reduced laryngoscopic evidence of laryngeal trauma compared with intubation with a standard-size ETT. DESIGN, SETTING, AND PARTICIPANTS: This double-blind randomized clinical trial studied patients 18 years and older undergoing elective thyroidectomy at an academic teaching hospital from October 15, 2012, through June 13, 2013. INTERVENTIONS: Patients were randomized to group 1 (standard-size ETT, 8.0 mm for men and 7.5 mm for women; n = 24) or group 2 (small ETT, 7.0 mm for men and 6.5 mm for women; n = 25). Patients were assessed preoperatively and at 24 hours and 3 weeks postoperatively. MAIN OUTCOMES AND MEASURES: Fiberoptic videolaryngoscopy with modified scoring system, voice assessment using the GRBAS (grade, roughness, breathiness, asthenia, strain) rating scale, vocal self-assessment using the 30-item Voice Handicap Index, and subjective pain score. RESULTS: At 24 hours, no significant differences were found between patients in groups 1 and 2 in change in GRBAS scores, change in laryngoscopic score (1.71 vs 1.76, P = .90), or postoperative pain score (3.3 vs 3.2, P = .91). At 3 weeks, no significant differences were found in changes in the 30-item Voice Handicap Index score (-2.2 vs -1.3, P = .74), GRBAS scores, or laryngoscopic score (0.25 vs 0.16, P = .67). CONCLUSIONS AND RELEVANCE: We did not find evidence that smaller ETT size for thyroidectomy has any significant effect on postoperative vocal outcomes, incidence of laryngeal trauma as assessed by laryngoscopy, or pain scores. However, because of the small sample size, our study may have been underpowered to detect small differences. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02136459. PMID- 26158870 TI - Electrocardiographic Pad for Efficient Cardiac MR Gating. AB - PURPOSE: To assess feasibility and reliability of electrocardiographic (ECG) gated cardiac magnetic resonance (MR) imaging with a simplified reusable electrode design that does not touch the skin. MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant study, a silicon positioner held four ECG leads and detected ECG signals without requiring shaving, adhesive, or removal of the gown. The patient lies down on the device and the patient's weight ensures good lead contact against patient's gown; electrode gel that soaks through the gown provides electrical contact with the skin. It was tested at 1.5 T on 12 volunteers and 52 patients by using double inversion recovery, steady state, fast gradient-echo time course perfusion, and delayed inversion recovery sequences. Paired Student t test was used to assess the significance of differences in durations to apply and remove ECG pad and standard leads. Image quality was assessed and rated on a four-point scale by two readers. The ECG signal quality obtained from pad and leads was rated on a five-point scale. Ventricular septal sharpness and signal-to-noise ratio were measured on images generated by ECG gating from pads and standard leads. RESULTS: Application and removal duration was 444 seconds with standard leads compared with 296 seconds with the ECG pad, and mean difference in setup time was 148 seconds (P = .005). Ventricular septal sharpness (1/slope) was 165 for ECG pad and 152 for standard leads (P = .3). Septal signal-to-noise ratio on images generated by cardiac gating with ECG pad was 38 +/- 12 (standard deviation) compared with 39 +/- 14 for standard leads (P = .7). The qualitative image quality score for ECG pad (3.9 +/- 0.19) was comparable to ECG leads (3.8 +/- 0.45; P = .47). The mean ECG signal qualitative scores were also comparable (pad vs leads, 4.9 +/- 0.43 vs 4.9 +/- 0.14, respectively; P = .9). Volunteers preferred the ECG pad and reported that it was comfortable and convenient. ECG pad was successful in 50 of 52 (96%) patients. Two patients, including one with large pleural effusions and another with ventricular tachycardia, were not successfully gated. CONCLUSION: This simplified approach to ECG gating is faster to set up and more convenient and comfortable for patients. PMID- 26158871 TI - China's rising hydropower demand challenges water sector. AB - Demand for hydropower is increasing, yet the water footprints (WFs) of reservoirs and hydropower, and their contributions to water scarcity, are poorly understood. Here, we calculate reservoir WFs (freshwater that evaporates from reservoirs) and hydropower WFs (the WF of hydroelectricity) in China based on data from 875 representative reservoirs (209 with power plants). In 2010, the reservoir WF totaled 27.9 * 10(9) m(3) (Gm(3)), or 22% of China's total water consumption. Ignoring the reservoir WF seriously underestimates human water appropriation. The reservoir WF associated with industrial, domestic and agricultural WFs caused water scarcity in 6 of the 10 major Chinese river basins from 2 to 12 months annually. The hydropower WF was 6.6 Gm(3) yr(-1) or 3.6 m(3) of water to produce a GJ (10(9) J) of electricity. Hydropower is a water intensive energy carrier. As a response to global climate change, the Chinese government has promoted a further increase in hydropower energy by 70% by 2020 compared to 2012. This energy policy imposes pressure on available freshwater resources and increases water scarcity. The water-energy nexus requires strategic and coordinated implementations of hydropower development among geographical regions, as well as trade-off analysis between rising energy demand and water use sustainability. PMID- 26158869 TI - Telomeric G-quadruplexes are a substrate and site of localization for human telomerase. AB - It has been hypothesized that G-quadruplexes can sequester the 3' end of the telomere and prevent it from being extended by telomerase. Here we purify and characterize stable, conformationally homogenous human telomeric G-quadruplexes, and demonstrate that human telomerase is able to extend parallel, intermolecular conformations in vitro. These G-quadruplexes align correctly with the RNA template of telomerase, demonstrating that at least partial G-quadruplex resolution is required. A highly purified preparation of human telomerase retains this extension ability, establishing that the core telomerase enzyme complex is sufficient for partial G-quadruplex resolution and extension. The parallel specific G-quadruplex ligand N-methyl mesoporphyrin IX (NMM) causes an increase in telomeric G-quadruplexes, and we show that telomerase colocalizes with a subset of telomeric G-quadruplexes in vivo. The ability of telomerase to partially unwind, extend and localize to these structures implies that parallel telomeric G-quadruplexes may play an important biological role. PMID- 26158872 TI - Development of a low fat fresh pork sausage based on chitosan with health claims: impact on the quality, functionality and shelf-life. AB - A low fat fresh pork sausage based on chitosan was developed with the objective of obtaining a new functional meat product with improved properties and health claims promoting cholesterol reduction. Sausages were formulated with chitosan (2%, w/w) and different fat levels (5%, 12.5% and 20%, w/w). The results indicated that incorporation of 2% chitosan into produced pork sausages with health claims of reduction of cholesterol is technologically feasible. In addition, the chitosan reduced the microbial growth, revealing interesting fat and water absorption capacities, reduced lipid oxidation, provided greater stability in terms of colorimetric parameters and promoted positive firmer texture and gumminess. The reduction of fat content to levels of 5% was positively achieved with the incorporation of chitosan. Sensorial analysis showed that panelists did not detect any significant difference in taste and any unfavorable effect on the sausage appearance as a consequence of chitosan addition and variation of fat. PMID- 26158874 TI - The Lung Microbiome: New Principles for Respiratory Bacteriology in Health and Disease. PMID- 26158875 TI - War and Peace: Possible Approaches to Reducing Intergroup Conflict. AB - We discuss four potential ways to reduce conflict between groups: consideration of future consequences, independent leadership, outgroup empathy, and coordination. We review relevant empirical findings for each method and discuss how each can be used to promote intergroup cooperation. PMID- 26158873 TI - Gap geometry dictates epithelial closure efficiency. AB - Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. PMID- 26158876 TI - Affect and Cognition. AB - One of the greatest puzzles of human nature concerns the poorly understood interplay between affect and cognition-the rational and emotional ways of dealing with the social world around us. Affect is a ubiquitous and powerful phenomenon in our lives, yet research on human affectivity has been neglected until quite recently. This article reviews traditional and contemporary approaches to this issue, and recent theoretical and empirical work exploring the links between affect and cognition is considered. The major achievements and shortcomings of this now-thriving research area are discussed, and the future prospects of psychological research on human affectivity are considered. PMID- 26158877 TI - Self-Enhancement: Food for Thought. AB - Self-enhancement denotes a class of psychological phenomena that involve taking a tendentiously positive view of oneself. We distinguish between four levels of self-enhancement-an observed effect, an ongoing process, a personality trait, and an underlying motive-and then use these distinctions to organize the wealth of relevant research. Furthermore, to render these distinctions intuitive, we draw an extended analogy between self-enhancement and the phenomenon of eating. Among the topics we address are (a) manifestations of self-enhancement, both obvious and subtle, and rival interpretations; (b) experimentally documented dynamics of affirming and threatening the ego; and (c) primacy of self-enhancement, considered alongside other intrapsychic phenomena, and across different cultures. Self-enhancement, like eating, is a fundamental part of human nature. PMID- 26158878 TI - In Pursuit of Happiness: Empirical Answers to Philosophical Questions. AB - In this article, we provide an overview of what various philosophers throughout the ages have claimed about the nature of happiness, and we discuss to what extent psychological science has been able to substantiate or refute their claims. We first address concerns raised by philosophers regarding the possibility, desirability, and justifiability of happiness and then turn to the perennial question of how to be happy. Integrating insights from great thinkers of the past with empirical findings from modern behavioral sciences, we review the conditions and causes of happiness. We conclude our discussion with some thoughts about the future of happiness studies. PMID- 26158879 TI - Ideology: Its Resurgence in Social, Personality, and Political Psychology. AB - We trace the rise, fall, and resurgence of political ideology as a topic of research in social, personality, and political psychology. For over 200 years, political belief systems have been classified usefully according to a single left right (or liberal-conservative) dimension that, we believe, possesses two core aspects: (a) advocating versus resisting social change and (b) rejecting versus accepting inequality. There have been many skeptics of the notion that most people are ideologically inclined, but recent psychological evidence suggests that left-right differences are pronounced in many life domains. Implicit as well as explicit preferences for tradition, conformity, order, stability, traditional values, and hierarchy-versus those for progress, rebelliousness, chaos, flexibility, feminism, and equality-are associated with conservatism and liberalism, respectively. Conservatives score consistently higher than liberals on measures of system justification. Furthermore, there are personality and lifestyle differences between liberals and conservatives as well as situational variables that induce either liberal or conservative shifts in political opinions. Our thesis is that ideological belief systems may be structured according to a left-right dimension for largely psychological reasons linked to variability in the needs to reduce uncertainty and threat. PMID- 26158880 TI - Persuasion: From Single to Multiple to Metacognitive Processes. AB - This article provides a brief overview of major developments in the history of contemporary persuasion theory. The first intuitive and empirical approaches to persuasion were guided by main-effect questions (e.g., are experts more persuasive than nonexperts?). Furthermore, researchers focused on only one process by which variables (e.g., emotion, source credibility) would have an impact (e.g., emotion affected attitudes by classical conditioning). As data began to accumulate, so many new theories and effects were uncovered that the discipline faced collapse from the numerous inconsistencies evident. In response to the reigning confusion of the previous era, contemporary multiprocess theories were proposed (e.g., the elaboration likelihood model). According to these more integrative approaches, any one variable could affect attitudes by different processes in different situations and thereby sometimes produce opposite effects. Finally, we describe the role of a recently discovered new contributor to persuasion: self-validation. Unlike previous mechanisms that focus on primary cognition, this new process emphasizes secondary or meta-cognition. PMID- 26158881 TI - Validation of a Clinical Test of Thoracolumbar Dissociation in Chronic Low Back Pain. AB - STUDY DESIGN: Clinical test validation. OBJECTIVES: Preliminary study of concurrent and discriminant validity of a clinical test of thoracolumbar dissociation. BACKGROUND: Control deficits of back muscles and trunk movement are common in chronic/recurrent low back pain (LBP). A reliable clinical test to rate an individual's ability to dissociate lumbopelvic movement from the thoracolumbar region has been described. This test rates the performance quality of 5 key aspects against criterion standards. METHODS: Concurrent validity was examined by comparison of clinical test scores (overall score and each individual criterion) against spine kinematics. Discriminant validity was evaluated by comparison of scores between pain-free controls and participants with LBP. A receiver operating characteristic curve was calculated to determine the optimal cutoff or score to differentiate between good and poor performers. RESULTS: Concurrent validity was supported by the significant correlation between the total score and motion of the T5 vertebra relative to the S1 vertebra (P<.05). Scores for some (4 correlations of 14 measures) but not all individual criteria were correlated with the kinematic features that each criterion was expected to reflect. Discriminant validity was supported by higher test scores for pain-free controls than for participants with LBP after 2 minutes of training (P = .045). Scores of less than 5.5 were more prevalent in the LBP group (pretraining LBP versus control, 72% versus 35%; P = .008; posttraining LBP versus control, 48% versus 16%; P = .018). CONCLUSION: This preliminary study of concurrent and discriminant validity of the test provides a foundation to further investigate its utility to characterize thoracolumbar movement patterns in individuals with LBP. PMID- 26158882 TI - Gait Retraining for Injured and Healthy Runners Using Augmented Feedback: A Systematic Literature Review. AB - STUDY DESIGN: Systematic literature review. OBJECTIVES: This review sought to determine the efficacy of real-time visual and/or auditory feedback for modifying kinematics and kinetics during running gait. BACKGROUND: Real-time visual and auditory feedback has gained popularity in the clinical and research settings. Rehabilitation time and injury prevention may be improved when clinicians are able to modify running mechanics in a patient population. METHODS: A thorough search of PubMed, CINAHL, and Web of Science from 1989 to January 2015 was performed. The search sought articles that examined real-time visual or auditory feedback for the purposes of modifying kinematics or kinetics in injured or healthy runners. Study design and methodological quality were rated using a 20 point scale. RESULTS: Ten studies were identified for inclusion in the review, 2 of high and 8 of moderate methodological quality. There was a consensus in the literature that the use of real-time feedback is effective in reducing variables related to ground reaction forces, as well as in positively modifying previously identified risky lower extremity kinematic movement patterns in healthy runners and those with patellofemoral pain and chronic exertional compartment syndrome. No one method of feedback was identified as being superior. Mirror and 2 dimensional video feedback were identified as potential methods for running-gait modification in a clinical setting. CONCLUSION: In conjunction with traditional therapeutic interventions, real-time auditory and visual feedback should be considered for treating injured runners or addressing potentially injurious running mechanics in a healthy population. PMID- 26158883 TI - The Development and Psychometric Properties of the Patient Self-Report Neck Functional Status Questionnaire (NFSQ). AB - STUDY DESIGN: Retrospective analysis of cross-sectional data. OBJECTIVE: To describe the development of a new self-report Neck Functional Status Questionnaire (NFSQ) and to assess its psychometric properties and practical application. The NFSQ was designed to assess functional status in patients with cervical (spine) disorders who seek outpatient therapy. BACKGROUND: Many patients seek outpatient therapy due to cervical disorders. Currently, no patient-reported outcome measures exist that capture the ability to perform functional activity in a manner that reflects the experience of this patient population. METHODS: Four hundred thirty-nine patients who were being treated for cervical disorders responded to a set of survey questions to assess activity-related functional outcomes associated with cervical disorders. Using item response theory, we assessed candidate items for unidimensionality and local independence, item fit, person separation, precision, targeting, and differential item functioning. We also compared discriminant validity of functional status measures estimated by the item response theory model (NFSQ fixed) and measures generated using a simulated computerized adaptive test (NFSQ computerized adaptive test). RESULTS: Based on expert opinion and subsequent processing and analyses, a final set of 28 items was used to develop the NFSQ. Unidimensionality and local independence were supported. The mean +/- SD sample ability level of 57.6 +/- 14.3 (scale range, 0 100) matched well with the mean item difficulty of the NFSQ of 51.3 +/- 7.4. Differential item functioning was negligible for levels of age group, sex, and symptom acuity. The NFSQ computerized adaptive test measures were as precise as the NFSQ fixed measures. CONCLUSION: Study results supported the preliminary validity of the 28-item NFSQ for use in assessing patients with different levels of functional status related to their cervical disorders in outpatient rehabilitation settings. PMID- 26158884 TI - First Reported Case of Primary Intrahepatic Cholangiocarcinoma with Pure Squamous Cell Histology: A Case Report. AB - BACKGROUND: In the United States, approximately 2500 cases of cholangiocarcinoma occur each year. The average incidence is 1 case/100 000 persons each year. Surgical resection is the mainstay for the treatment of cholangiocarcinoma. The result of surgery depends on location of the tumor, extent of tumor penetration of the bile duct, tumor-free resection margins, and lymph node and distant metastases. There has been an increase in the incidence of intrahepatic cholangiocarcinoma (IHCC) globally over a period of 30 years from 0.32/100 000 to 0.85/100 000 persons each year. Epidemiologically, the incidence of IHCC has been increasing in the U.S. from year 1973 to 2010. CASE REPORT: We are reporting a first case of primary intrahepatic cholangiocarcinoma of pure squamous cell histology. A 64-year-old man presented with right upper-quadrant pain, jaundice, and weight loss. Imaging studies revealed a large hepatobiliary mass, intrahepatic bile duct dilation, normal common duct, and absence of choledocholithiasis. Delayed-contrast magnetic resonance imaging of the abdomen showed peripheral enhancement of the central lesion, which is typical of cholangiocarcinoma in contrast to hepatocellular carcinoma or metastasis. Cancer antigen 19-9 was markedly elevated. Liver function tests were deranged. Endoscopic retrograde cholangiopancreatography showed high degree of left hepatic duct stricture. Brush cytopathology was positive for atypia. The patient underwent exploratory laparotomy for en-bloc resection of the hepatobiliary mass with colon resection, liver resection, and cholecystectomy. Histology revealed keratinizing squamous cell carcinoma. Based on these findings, a definitive diagnosis of well-differentiated squamous cell carcinoma of the intrahepatic bile duct was made. CONCLUSIONS: Squamous cell carcinoma of the biliary tree is very rare and the majority of tumors are adenocarcinomas. Cholangiocarcinomas containing a squamous cell component have a poor prognosis due to its aggressive behavior. However, prognosis of cholangiocarcinoma with pure SCC histology is unknown because this is the first case in the literature. PMID- 26158886 TI - Patient perceptions of severe COPD and transitions towards death: a qualitative study identifying milestones and developing key opportunities. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a slowly disabling illness, with functional limitations and a high burden of symptoms. Palliative care services focus on quality of life for those facing life-limiting illness. Patients with COPD often see their illness as a 'way of life', not as a life threatening illness, which makes the interface difficult. AIMS: The aim of this study was to explore the experience of patients with advanced COPD after a life threatening event, particularly focusing on end-of-life issues. METHODS: Qualitative methods were used to capture patient experiences. Patients admitted for noninvasive ventilation for COPD were recruited and interviewed in their homes following discharge. The interview schedule explored the participants' understanding of their illness, concerns and plans, exploring end-of-life issues and perceptions of palliative care. RESULTS: Participants were recruited until themes were saturated. Six transition points or milestones emerged: loss of recreation, home environment, episodes of acute care, long-term oxygen treatment, panic attacks, and assistance with self-care were common themes throughout the narratives. CONCLUSIONS: Milestones accumulate in no particular order. They can be easily recognised and allow health professionals to develop a common language with their patients. In advancing COPD, milestones may trigger the reassessment of goals of care and integration of a palliative approach. PMID- 26158885 TI - Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine. AB - Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA-spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients. PMID- 26158887 TI - Cortical Drive to Breathe during Wakefulness in Patients with Obstructive Sleep Apnea Syndrome. AB - STUDY OBJECTIVES: The obstructive sleep apnea syndrome (OSAS) involves recurrent sleep-related upper airways (UA) collapse. UA mechanical properties and neural control are altered, imposing a mechanical load on inspiration. UA collapse does not occur during wakefulness, hence arousal-dependent compensation. Experimental inspiratory loading in normal subjects elicits respiratory-related cortical activity. The objective of this study was to test whether awake OSAS patients would exhibit a similar cortical activity. DESIGN: Descriptive physiology study. SETTING: Sleep laboratory in a large university affiliated tertiary hospital. PATIENTS: 26 patients with moderate OSAS according to polysomnography (5 < apnea hypopnea index [AHI] <= 30, n = 14) or severe OSAS (AHI > 30, n = 12); 13 non OSAS patients for comparison. INTERVENTIONS: None. MEASUREMENTS: Respiratory time locked electroencephalographic segments ensemble averaged and analyzed for slow premotor potentials preceding inspiration ("pre-inspiratory potentials" [PIPs]). RESULTS: PIPs were present in 1/13 controls and 11/26 patients (P = 0.0336; 4/14 "moderate" and 7/12 "severe" patients). Awake OSAS patients therefore exhibit respiratory-related cortical activity during quiet breathing significantly more frequently than non-OSAS individuals. The corresponding PIPs resemble those observed during prepared voluntary inspirations and in response to experimental inspiratory loads in normal subjects, which involve a cortical network comprising the supplementary motor area. CONCLUSIONS: A respiratory-related cortical activity could contribute to the increased neural drive to upper airway and to inspiratory muscles that has previously been described in obstructive sleep apnea, and could therefore contribute to the arousal-dependent compensation of upper airway abnormalities. Whether or not such cortical compensatory mechanisms have cognitive consequences remains to be determined. PMID- 26158888 TI - Negative Expiratory Pressure Technique: An Awake Test to Measure Upper Airway Collapsibility in Adolescents. AB - STUDY OBJECTIVES: Upper airway (UA) collapsibility is a major pathophysiologic feature of the obstructive sleep apnea syndrome (OSAS). In adolescents, it is measured by obtaining the slope of pressure-flow relationship (SPF) while applying negative nasal pressure during sleep. An easier technique to assess UA collapsibility, consisting of application of negative expiratory pressure (NEP) during wakefulness, has demonstrated differences between control and OSAS subjects. We hypothesized that the NEP technique would correlate with SPF as a measurement of UA collapsibility in adolescents. DESIGN: During wakefulness, NEP of -5 cm H2O in the seated and supine position was applied during the first second of expiration. The area under the expiratory flow-volume curve during NEP was compared to tidal breathing (RatioNEP). In addition, adolescents underwent SPF measurements during sleep. Two SPF techniques were performed to measure the activated and relatively hypotonic UA. SETTING: Pediatric sleep laboratory. PARTICIPANTS: Seven adolescents with OSAS and 20 controls. RESULTS: In the seated position, there was a correlation between RatioNEP and both hypotonic SPF (r = 0.39, P = 0.04) and activated SPF (r = -0.62, P = 0.001). In the supine position, there was a correlation between RatioNEP and activated SPF (r = -0.43, P = 0.03) and a trend for hypotonic SPF (r = -0.38, P = 0.06). CONCLUSIONS: The negative expiratory pressure (NEP) technique correlates with the hypotonic and activated slope of pressure-flow relationship measurements. The seated position showed the strongest correlation. The NEP technique can be used as an alternative method to evaluate upper airway collapsibility in adolescents. PMID- 26158889 TI - Efficacy of Cognitive Behavioral Therapy for Insomnia in Adolescents: A Randomized Controlled Trial with Internet Therapy, Group Therapy and A Waiting List Condition. AB - STUDY OBJECTIVES: To investigate the efficacy of cognitive behavioral therapy for insomnia (CBTI) in adolescents. DESIGN: A randomized controlled trial of CBTI in group therapy (GT), guided internet therapy (IT), and a waiting list (WL), with assessments at baseline, directly after treatment (post-test), and at 2 months follow-up. SETTING: Diagnostic interviews were held at the laboratory of the Research Institute of Child Development and Education at the University of Amsterdam. Treatment for GT occurred at the mental health care center UvAMinds in Amsterdam, the Netherlands. PARTICIPANTS: One hundred sixteen adolescents (mean age = 15.6 y, SD = 1.6 y, 25% males) meeting DSM-IV criteria for insomnia, were randomized to IT, GT, or WL. INTERVENTIONS: CBTI of 6 weekly sessions, consisted of psychoeducation, sleep hygiene, restriction of time in bed, stimulus control, cognitive therapy, and relaxation techniques. GT was conducted in groups of 6 to 8 adolescents, guided by 2 trained sleep therapists. IT was applied through an online guided self-help website with programmed instructions and written feedback from a trained sleep therapist. MEASUREMENTS AND RESULTS: Sleep was measured with actigraphy and sleep logs for 7 consecutive days. Symptoms of insomnia and chronic sleep reduction were measured with questionnaires. Results showed that adolescents in both IT and GT, compared to WL, improved significantly on sleep efficiency, sleep onset latency, wake after sleep onset, and total sleep time at post-test, and improvements were maintained at follow-up. Most of these improvements were found in both objective and subjective measures. Furthermore, insomnia complaints and symptoms of chronic sleep reduction also decreased significantly in both treatment conditions compared to WL. Effect sizes for improvements ranged from medium to large. A greater proportion of participants from the treatment conditions showed high end-state functioning and clinically significant improvement after treatment and at follow-up compared to WL. CONCLUSIONS: This study is the first randomized controlled trial that provides evidence that cognitive behavioral therapy for insomnia is effective for the treatment of adolescents with insomnia, with medium to large effect sizes. There were small differences between internet and group therapy, but both treatments reached comparable endpoints. CLINICAL TRIAL REGISTRATION: This study was part of the clinical trial: Effectiveness of cognitive behavioral therapy for sleeplessness in adolescents; URL: http://www.isrctn.com/ISRCTN33922163; registration: ISRCTN33922163. PMID- 26158890 TI - Short Sleep Makes Declarative Memories Vulnerable to Stress in Humans. AB - STUDY OBJECTIVE: This study sought to investigate the role of nocturnal sleep duration for the retrieval of oversleep consolidated memories, both prior to and after being cognitively stressed for ~30 minutes the next morning. DESIGN: Participants learned object locations (declarative memory task comprising 15 card pairs) and a finger tapping sequence (procedural memory task comprising 5 digits) in the evening. After learning, participants either had a sleep opportunity of 8 hours (between ~23:00 and ~07:00, full sleep condition) or they could sleep between ~03:00 and ~07:00 (short sleep condition). Retrieval of both memory tasks was tested in the morning after each sleep condition, both before (~08:30) and after being stressed (~09:50). SETTING: Sleep laboratory. PARTICIPANTS: 15 healthy young men. RESULTS: The analyses demonstrated that oversleep memory changes did not differ between sleep conditions. However, in their short sleep condition, following stress hallmarked by increased subjective stress feelings, the men were unable to maintain their pre-stress performance on the declarative memory task, whereas their performance on the procedural memory task remained unchanged. While men felt comparably subjectively stressed by the stress intervention, overall no differences between pre- and post-stress recalls were observed following a full night of sleep. CONCLUSIONS: The findings suggest that 8-h sleep duration, within the range recommended by the US National Sleep Foundation, may not only help consolidate newly learned procedural and declarative memories, but also ensure full access to both during periods of subjective stress. PMID- 26158891 TI - Narcolepsy in African Americans. AB - STUDY OBJECTIVES: Although narcolepsy affects 0.02-0.05% of individuals in various ethnic groups, clinical presentation in different ethnicities has never been fully characterized. Our goal was to study phenotypic expression across ethnicities in the United States. DESIGN/SETTING: Cases of narcolepsy from 1992 to 2013 were identified from searches of the Stanford Center for Narcolepsy Research database. International Classification of Sleep Disorders, Third Edition diagnosis criteria for type 1 and type 2 narcolepsy were used for inclusion, but subjects were separated as with and without cataplexy for the purpose of data presentation. Information extracted included demographics, ethnicity and clinical data, HLA-DQB1*06:02, polysomnography (PSG), multiple sleep latency test (MSLT) data, and cerebrospinal fluid (CSF) hypocretin-1 level. PATIENTS: 182 African Americans, 839 Caucasians, 35 Asians, and 41 Latinos with narcolepsy. RESULTS: Sex ratio, PSG, and MSLT findings did not differ across ethnicities. Epworth Sleepiness Scale (ESS) score was higher and age of onset of sleepiness earlier in African Americans compared with other ethnicities. HLA-DQB1*06:02 positivity was higher in African Americans (91.0%) versus others (76.6% in Caucasians, 80.0% in Asians, and 65.0% in Latinos). CSF hypocretin-1 level, obtained in 222 patients, was more frequently low (<= 110 pg/ml) in African Americans (93.9%) versus Caucasians (61.5%), Asians (85.7%) and Latinos (75.0%). In subjects with low CSF hypocretin-1, African Americans (28.3%) were 4.5 fold more likely to be without cataplexy when compared with Caucasians (8.1%). CONCLUSIONS: Narcolepsy in African Americans is characterized by earlier symptom onset, higher Epworth Sleepiness Scale score, higher HLA-DQB1*06:02 positivity, and low cerebrospinal fluid hypocretin-1 level in the absence of cataplexy. In African Americans, more subjects without cataplexy have type 1 narcolepsy. PMID- 26158892 TI - Daytime Napping and the Risk of Cardiovascular Disease and All-Cause Mortality: A Prospective Study and Dose-Response Meta-Analysis. AB - STUDY OBJECTIVES: To summarize evidence about the association between daytime napping and the risk of cardiovascular disease and all-cause mortality, and to quantify the potential dose-response relation. DESIGN: Meta-analysis of prospective cohort studies. METHODS AND RESULTS: Electronic databases were searched for articles published up to December 2014 using the terms nap, cardiovascular disease, and all-cause mortality. We selected well-adjusted prospective cohort studies reporting risk estimates for cardiovascular disease and all-cause mortality related to napping. Eleven prospective cohort studies were identified with 151,588 participants (1,625,012 person-years) and a mean follow-up period of 11 years (60% women, 5,276 cardiovascular events, and 18,966 all-cause deaths). Pooled analysis showed that a long daytime nap (>= 60 min/day) was associated with a higher risk of cardiovascular disease (rate ratio [RR]: 1.82 [1.22-2.71], P = 0.003, I(2) = 37%) compared with not napping. All-cause mortality was associated with napping for >= 60 min/day (RR: 1.27 [1.11-1.45], P < 0.001, I(2) = 0%) compared with not napping. In contrast, napping for < 60 min/day was not associated with cardiovascular disease (P = 0.98) or all-cause mortality (P = 0.08). Meta-analysis demonstrated a significant J-curve dose response relation between nap time and cardiovascular disease (P for nonlinearity = 0.01). The RR initially decreased from 0 to 30 min/day. Then it increased slightly until about 45 min/day, followed by a sharp increase at longer nap times. There was also a positive linear relation between nap time and all-cause mortality (P for non-linearity = 0.97). CONCLUSIONS: Nap time and cardiovascular disease may be associated via a J-curve relation. Further studies are needed to confirm the efficacy of a short nap. PMID- 26158893 TI - Diet/Energy Balance Affect Sleep and Wakefulness Independent of Body Weight. AB - STUDY OBJECTIVES: Excessive daytime sleepiness commonly affects obese people, even in those without sleep apnea, yet its causes remain uncertain. We sought to determine whether acute dietary changes could induce or rescue wake impairments independent of body weight. DESIGN: We implemented a novel feeding paradigm that generates two groups of mice with equal body weight but opposing energetic balance. Two subsets of mice consuming either regular chow (RC) or high-fat diet (HFD) for 8 w were switched to the opposite diet for 1 w. Sleep recordings were conducted at Week 0 (baseline), Week 8 (pre-diet switch), and Week 9 (post-diet switch) for all groups. Sleep homeostasis was measured at Week 8 and Week 9. PARTICIPANTS: Young adult, male C57BL/6J mice. MEASUREMENTS AND RESULTS: Differences in total wake, nonrapid eye movement (NREM), and rapid eye movement (REM) time were quantified, in addition to changes in bout fragmentation/consolidation. At Week 9, the two diet switch groups had similar body weight. However, animals switched to HFD (and thus gaining weight) had decreased wake time, increased NREM sleep time, and worsened sleep/wake fragmentation compared to mice switched to RC (which were in weight loss). These effects were driven by significant sleep/wake changes induced by acute dietary manipulations (Week 8 -> Week 9). Sleep homeostasis, as measured by delta power increase following sleep deprivation, was unaffected by our feeding paradigm. CONCLUSIONS: Acute dietary manipulations are sufficient to alter sleep and wakefulness independent of body weight and without effects on sleep homeostasis. PMID- 26158894 TI - Modafinil Increases Awake EEG Activation and Improves Performance in Obstructive Sleep Apnea during Continuous Positive Airway Pressure Withdrawal. AB - OBJECTIVES: We examined the changes in waking electroencephalography (EEG) biomarkers with modafinil during continuous positive airway pressure (CPAP) withdrawal in patients with obstructive sleep apnea (OSA) to investigate neurophysiological evidence for potential neurocognitive improvements. DESIGN: Randomized double-blind placebo-controlled crossover study. CPAP was used for the first night and then withdrawn for 2 subsequent nights. Each morning after the 2 CPAP withdrawal nights, patients received either 200 mg modafinil or placebo. After a 5-w washout, the procedure repeated with the crossover drug. SETTINGS: University teaching hospital. PARTICIPANTS: Stable CPAP users (n = 23 men with OSA). MEASUREMENT AND RESULTS: Karolinska Drowsiness Test (KDT) (awake EEG measurement with eyes open and closed), Psychomotor Vigilance Task (PVT), and driving simulator Performance were assessed bihourly during the 3 testing days following CPAP treatment and CPAP withdrawal nights. Compared to placebo, modafinil significantly increased awake EEG activation (faster EEG frequency) with increased alpha/delta (A/D) ratio (P < 0.0001) and fast ratio = (alpha+beta)/(delta+theta) (P < 0.0001) across the 2 days of CPAP withdrawal. The A/D ratio significantly correlated with the driving simulator response time (P = 0.015), steering variation (P = 0.002), and PVT reaction time (P = 0.006). In contrast, individual EEG band power of alpha, beta, theta, and delta did not correlate with any neurocognitive performance. CONCLUSIONS: Modafinil administration during continuous positive airway pressure (CPAP) withdrawal increased awake EEG activation, which correlated to improved performance. This study provides supporting neurophysiological evidence that modafinil is a potential short-term treatment option during acute CPAP withdrawal. PMID- 26158895 TI - Upper Airway Stimulation for Obstructive Sleep Apnea: Durability of the Treatment Effect at 18 Months. AB - OBJECTIVE: To determine the stability of improvement in polysomnographic measures of sleep disordered breathing, patient reported outcomes, the durability of hypoglossal nerve recruitment and safety at 18 months in the Stimulation Treatment for Apnea Reduction (STAR) trial participants. DESIGN: Prospective multicenter single group trial with participants serving as their own controls. SETTING: Twenty-two community and academic sleep medicine and otolaryngology practices. MEASUREMENTS: Primary outcome measures were the apnea-hypopnea index (AHI) and the 4% oxygen desaturation index (ODI). Secondary outcome measures were the Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire (FOSQ), and oxygen saturation percent time < 90% during sleep. Stimulation level for each participant was collected at three predefined thresholds during awake testing. Procedure- and/or device-related adverse events were reviewed and coded by the Clinical Events Committee. RESULTS: The median AHI was reduced by 67.4% from the baseline of 29.3 to 9.7/h at 18 mo. The median ODI was reduced by 67.5% from 25.4 to 8.6/h at 18 mo. The FOSQ and ESS improved significantly at 18 mo compared to baseline values. The functional threshold was unchanged from baseline at 18 mo. Two participants experienced a serious device related adverse event requiring neurostimulator repositioning and fixation. No tongue weakness reported at 18 mo. CONCLUSION: Upper airway stimulation via the hypoglossal nerve maintained a durable effect of improving airway stability during sleep and improved patient reported outcomes (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire) without an increase of the stimulation thresholds or tongue injury at 18 mo of follow-up. PMID- 26158896 TI - Validation of Sleep-Tracking Technology Compared with Polysomnography in Adolescents. AB - STUDY OBJECTIVES: To evaluate the accuracy in measuring nighttime sleep of a fitness tracker (Jawbone UP) compared to polysomnography (PSG). DESIGN: Jawbone UP and PSG data were simultaneously collected from adolescents during an overnight laboratory recording. Agreements between Jawbone UP and PSG sleep outcomes were analyzed using paired t tests and Bland-Altman plots. Multiple regressions were used to investigate which PSG sleep measures predicted Jawbone UP "Sound sleep" and "Light sleep." SETTING: SRI International Human Sleep Laboratory. PARTICIPANTS: Sixty-five healthy adolescents (28 females, mean age +/ standard deviation [SD]: 15.8 +/- 2.5 y). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Outcomes showed good agreements between Jawbone UP and PSG for total sleep time (mean differences +/- SD: -10.0 +/- 20.5 min), sleep efficiency (mean differences +/- SD: -1.9 +/- 4.2 %), and wake after sleep onset (WASO) (mean differences +/- SD: 10.6 +/- 14.7 min). Overall, Jawbone UP overestimated PSG total sleep time and sleep efficiency and underestimated WASO but differences were small and, on average, did not exceed clinically meaningful cutoffs of > 30 min for total sleep time and > 5% for sleep efficiency. Multiple regression models showed that Jawbone UP "Sound sleep" measure was predicted by PSG time in N2 (beta = 0.25), time in rapid eye movement (beta = 0.29), and arousal index (beta = -0.34). Jawbone UP "Light sleep" measure was predicted by PSG time in N2 (beta = 0.48), time in N3 (beta = 0.49), arousal index (beta = 0.38) and awakening index (beta = 0.28). Jawbone UP showed a progression from slight overestimation to underestimation of total sleep time and sleep efficiency with advancing age. All relationships were similar in boys and girls. CONCLUSIONS: Jawbone UP shows good agreement with polysomnography in measures of total sleep time and wake after sleep onset in adolescent boys and girls. Further validation is needed in other age groups and clinical populations before advocating use of these inexpensive and easy-to-use devices in clinical sleep medicine and research. PMID- 26158898 TI - New streams and springs after the 2014 Mw6.0 South Napa earthquake. AB - Many streams and springs, which were dry or nearly dry before the 2014 Mw6.0 South Napa earthquake, started to flow after the earthquake. A United States Geological Survey stream gauge also registered a coseismic increase in discharge. Public interest was heightened by a state of extreme drought in California. Since the new flows were not contaminated by pre-existing surface water, their composition allowed unambiguous identification of their origin. Following the earthquake we repeatedly surveyed the new flows, collecting data to test hypotheses about their origin. We show that the new flows originated from groundwater in nearby mountains released by the earthquake. The estimated total amount of new water is ~ 10(6) m(3), about 1/40 of the annual water use in the Napa-Sonoma area. Our model also makes a testable prediction of a post-seismic decrease of seismic velocity in the shallow crust of the affected region. PMID- 26158897 TI - MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing. AB - Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-beta signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis. PMID- 26158899 TI - Ebselen inhibits QSOX1 enzymatic activity and suppresses invasion of pancreatic and renal cancer cell lines. AB - Quiescin sulfhydryl oxidase 1 (QSOX1) is a highly conserved disulfide bond generating enzyme that is overexpressed in diverse tumor types. Its enzymatic activity promotes the growth and invasion of tumor cells and alters extracellular matrix composition. In a nude mouse-human tumor xenograft model, tumors containing shRNA for QSOX1 grew significantly more slowly than controls, suggesting that QSOX1 supports a proliferative phenotype in vivo. High throughput screening experiments identified ebselen as an in vitro inhibitor of QSOX1 enzymatic activity. Ebselen treatment of pancreatic and renal cancer cell lines stalled tumor growth and inhibited invasion through Matrigel in vitro. Daily oral treatment with ebselen resulted in a 58% reduction in tumor growth in mice bearing human pancreatic tumor xenografts compared to controls. Mass spectrometric analysis of ebselen-treated QSOX1 mechanistically revealed that C165 and C237 of QSOX1 covalently bound to ebselen. This report details the anti neoplastic properties of ebselen in pancreatic and renal cancer cell lines. The results here offer a "proof-of-principle" that enzymatic inhibition of QSOX1 may have clinical relevancy. PMID- 26158900 TI - miR-17 regulates melanoma cell motility by inhibiting the translation of ETV1. AB - Melanoma is an aggressive malignancy with a high metastatic potential. microRNA 17 (miR-17) is a member of the oncogenic miR-17/92 cluster. Here we study the effect of miR-17 on melanoma cell motility. Over expression of the mature or pri microRNA form of miR-17 in WM-266-4 and 624mel melanoma lines enhances cell motility, evident in both wound healing and transwell migration assays. TargetScan algorithm predicts the PEA3-subfamily member ETV1 as a direct target of miR-17. Indeed, a 3-4-fold decrease of ETV1 protein levels are observed following miR-17 transfection into the various melanoma lines, with no significant change in ETV1 mRNA expression. Dual luciferase experiments demonstrate direct binding of miR-17 to the 3'-untranslated region of ETV1, confirmed by abolishing point mutations in the putative binding site. These combined results suggest regulation of ETV1 by miR-17 by a direct translational repression. Further, in both melanoma cell lines ETV1 knockdown by selective siRNA successfully pheno-copies the facilitated cell migration, while overexpression of ETV1 inhibits cell motility and migration. Altered ETV1 expression does not affect melanoma net-proliferation. In conclusion, we show a new role for miR-17 in melanoma, facilitating cell motility, by targeting the translation of ETV1 protein, which may support the development of metastasis. PMID- 26158902 TI - IRX1 hypomethylation in osteosarcoma metastasis. PMID- 26158901 TI - Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. AB - Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC. PMID- 26158904 TI - Can highly sensitive antimullerian hormone testing predict failed response to ovarian stimulation? AB - OBJECTIVE: To determine whether a newer commercially available antimullerian hormone (AMH) enzyme-linked immunosorbent assay (picoAMH ELISA, AnshLabs) with a lower threshold of detection is predictive of successful ovarian stimulation in a population of women with diminished ovarian reserve (DOR). DESIGN: Retrospective case-control study. SETTING: University-based IVF program. PATIENT(S): Cases were patients whose first IVF cycle was cancelled for lack of ovarian response (<3 follicles; n = 24). Controls were patients with DOR (early follicular FSH of >=10 IU/L), whose first cycle resulted in aspiration of at least 3 oocytes (n = 24). INTERVENTION(S): Frozen serum samples collected during routine clinical care between 2008 and 2012 before starting IVF were analyzed for AMH using the picoAMH ELISA. MAIN OUTCOME MEASURE(S): Serum AMH levels in patients who successfully reached oocyte retrieval compared with patients with a failed controlled ovarian hyperstimulation (COH) cycle. Receiver operator curve analysis was used to identify a predictive threshold AMH value. RESULT(S): No demographic differences were found between groups. The successful group had a higher antral follicle count (8.5 vs. 6) and higher AMH levels (847 vs. 406 pg/mL). The AMH level correlated with the antral follicle count (R = 0.61). The AMH level of >500 pg/mL had 83.3% sensitivity and 70.8% specificity to detect patients who proceeded to successful oocyte retrieval. Below AMH levels of 100 pg/mL, no patients achieved oocyte retrieval. CONCLUSION(S): Due to a lower threshold of detection, picoAMH may be able to predict successful ovarian stimulation among women with DOR using a threshold of 500 pg/mL, with good sensitivity and specificity. PMID- 26158905 TI - Reliability of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy and American Society for Reproductive Medicine classification systems for congenital uterine anomalies detected using three-dimensional ultrasonography. AB - OBJECTIVE: To estimate the inter-rater/intrarater reliability of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE-ESGE) classification of congenital uterine malformations and to compare the results obtained with the reliability of the American Society for Reproductive Medicine (ASRM) classification supplemented with additional morphometric criteria. DESIGN: Reliability/agreement study. SETTING: Private clinic. PATIENT(S): Uterine malformations (n = 50 patients, consecutively included) and normal uterus (n = 62 women, randomly selected) constituted the study. These were classified based on real-time three-dimensional ultrasound single volume transvaginal (or transrectal in the case of virgins, 4 cases) ultrasonography findings, which were assessed by an expert rater based on the ESHRE-ESGE criteria. The samples were obtained from women of reproductive age. INTERVENTION(S): Unprocessed three-dimensional datasets were independently evaluated offline by two experienced, blinded raters using both classification systems. MAIN OUTCOME MEASURE(S): The kappa-values and proportions of agreement. RESULT(S): Standardized interpretation indicated that the ESHRE-ESGE system has substantial/good or almost perfect/very good reliability (kappa >0.60 and >0.80), but the interpretation of the clinically relevant cutoffs of kappa-values showed insufficient reliability for clinical use (kappa < 0.90), especially in the diagnosis of septate uterus. The ASRM system had sufficient reliability (kappa > 0.95). CONCLUSION(S): The low reliability of the ESHRE-ESGE system may lead to a lack of consensus about the management of common uterine malformations and biased research interpretations. The use of the ASRM classification, supplemented with simple morphometric criteria, may be preferred if their sufficient reliability can be confirmed real-time in a large sample size. PMID- 26158906 TI - Evaluating gammaH2AX in spermatozoa from male infertility patients. AB - OBJECTIVE: To investigate whether gammaH2AX levels were different in the spermatozoa of healthy men compared with infertility patients, and to assess the possible correlations between gammaH2AX and conventional semen parameters and double-stranded breaks (DSBs) identified with the use of comet assay. DESIGN: Prospective study. SETTING: Clinical laboratory. PATIENT(S): Semen from 100 male infertile patients and 100 healthy sperm donors. INTERVENTION(S): Human sperm samples were analyzed in terms of World Health Organization parameters. The gammaH2AX levels were detected by means of flow cytometry. DSBs of sperm were detected by means of comet assay. Morphology slides were made and the sperm morphology assessed according to strict criteria. MAIN OUTCOME MEASURE(S): Conventional semen analyses, gammaH2AX levels in sperm, DNA DSBs in sperm, and correlations among gammaH2AX, conventional semen analyses, and DSBs. RESULT(S): Concentration, viability, motility, and normal sperm morphology were significantly lower in male infertility patients compared with healthy men. Also, gammaH2AX levels and the number of DSBs were significantly higher in the sperm of infertile subjects compared with healthy men. gammaH2AX levels correlated negatively with conventional semen parameters and positively with DSBs. A threshold gammaH2AX level of 18.55% was identified as a cutoff value to discriminate infertile subjects from fertile control subjects with a specificity of 86.0% and a sensitivity of 83.0%. The positive and negative predictive values of the 18.55% gammaH2AX threshold were high: 87.7% and 85.5%, respectively. CONCLUSION(S): gammaH2AX levels were higher in the sperm of male infertility patients than in healthy men. gammaH2AX levels in sperm, as evaluated with the use of flow cytometry, might be a useful biomarker for evaluating DSBs in human spermatozoa. PMID- 26158907 TI - Donor conception from the viewpoint of the child: positives, negatives, and promoting the welfare of the child. AB - Use of donor egg and donor sperm has made parenthood a possibility for many who could not achieve it through natural conception. The use of donor gametes may also permit prospective parents to mitigate a number of health problems for the hoped-for child. Promoting the welfare of the hoped-for child, however, includes not only the consideration of good physical health but also necessitates consideration of psychological, emotional, and social well-being. This paper will review the impact of donor conception from the viewpoint of the resulting child including the psychological, emotional, and social well-being of donor-conceived children. It will discuss the topic of disclosure and closely consider the expansion of donor conception to older parents from the viewpoint of the child. PMID- 26158908 TI - Perovskite solar cell using a two-dimensional titania nanosheet thin film as the compact layer. AB - The compact layer plays an important role in conducting electrons and blocking holes in perovskite solar cells (PSCs). Here, we use a two-dimensional titania nanosheet (TNS) thin film as the compact layer in CH3NH3PbI3 PSCs. TNS thin films with thicknesses ranging from 8 to 75 nm were prepared by an electrophoretic deposition method from a dilute TNS/tetrabutylammonium hydroxide solution. The TNS thin films contact the fluorine-doped tin oxide grains perfectly. Our results show that a 8-nm-thick TNS film is sufficient for acting as the compact layer. Currently, the PSC with a TNS compact layer has a high efficiency of 10.7% and relatively low hysteresis behavior. PMID- 26158909 TI - Lansoprazole is an antituberculous prodrug targeting cytochrome bc1. AB - Better antibiotics capable of killing multi-drug-resistant Mycobacterium tuberculosis are urgently needed. Despite extensive drug discovery efforts, only a few promising candidates are on the horizon and alternative screening protocols are required. Here, by testing a panel of FDA-approved drugs in a host cell-based assay, we show that the blockbuster drug lansoprazole (Prevacid), a gastric proton-pump inhibitor, has intracellular activity against M. tuberculosis. Ex vivo pharmacokinetics and target identification studies reveal that lansoprazole kills M. tuberculosis by targeting its cytochrome bc1 complex through intracellular sulfoxide reduction to lansoprazole sulfide. This novel class of cytochrome bc1 inhibitors is highly active against drug-resistant clinical isolates and spares the human H(+)K(+)-ATPase thus providing excellent opportunities for targeting the major pathogen M. tuberculosis. Our finding provides proof of concept for hit expansion by metabolic activation, a powerful tool for antibiotic screens. PMID- 26158911 TI - Neighborhood greenspace and health in a large urban center. AB - Studies have shown that natural environments can enhance health and here we build upon that work by examining the associations between comprehensive greenspace metrics and health. We focused on a large urban population center (Toronto, Canada) and related the two domains by combining high-resolution satellite imagery and individual tree data from Toronto with questionnaire-based self reports of general health perception, cardio-metabolic conditions and mental illnesses from the Ontario Health Study. Results from multiple regressions and multivariate canonical correlation analyses suggest that people who live in neighborhoods with a higher density of trees on their streets report significantly higher health perception and significantly less cardio-metabolic conditions (controlling for socio-economic and demographic factors). We find that having 10 more trees in a city block, on average, improves health perception in ways comparable to an increase in annual personal income of $10,000 and moving to a neighborhood with $10,000 higher median income or being 7 years younger. We also find that having 11 more trees in a city block, on average, decreases cardio metabolic conditions in ways comparable to an increase in annual personal income of $20,000 and moving to a neighborhood with $20,000 higher median income or being 1.4 years younger. PMID- 26158910 TI - Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol. AB - The high pathogenicity of the Ebola virus reflects multiple concurrent processes on infection. Among other important determinants, Ebola fusogenic glycoprotein (GP) has been associated with the detachment of infected cells and eventually leads to vascular leakage and haemorrhagic fever. Here we report that the membrane-anchored GP is sufficient to induce the detachment of adherent cells. The results show that the detachment induced through either full-length GP1,2 or the subunit GP2 depends on cholesterol and the structure of the transmembrane domain. These data reveal a novel molecular mechanism in which GP regulates Ebola virus assembly and suggest that cholesterol-reducing agents could be useful as therapeutics to counteract GP-mediated cell detachment. PMID- 26158912 TI - Enhancing the Effectiveness of Work Groups and Teams. AB - Teams of people working together for a common purpose have been a centerpiece of human social organization ever since our ancient ancestors first banded together to hunt game, raise families, and defend their communities. Human history is largely a story of people working together in groups to explore, achieve, and conquer. Yet, the modern concept of work in large organizations that developed in the late 19th and early 20th centuries is largely a tale of work as a collection of individual jobs. A variety of global forces unfolding over the last two decades, however, has pushed organizations worldwide to restructure work around teams, to enable more rapid, flexible, and adaptive responses to the unexpected. This shift in the structure of work has made team effectiveness a salient organizational concern. Teams touch our lives everyday and their effectiveness is important to well-being across a wide range of societal functions. There is over 50 years of psychological research-literally thousands of studies-focused on understanding and influencing the processes that underlie team effectiveness. Our goal in this monograph is to sift through this voluminous literature to identify what we know, what we think we know, and what we need to know to improve the effectiveness of work groups and teams. We begin by defining team effectiveness and establishing the conceptual underpinnings of our approach to understanding it. We then turn to our review, which concentrates primarily on topics that have well-developed theoretical and empirical foundations, to ensure that our conclusions and recommendations are on firm footing. Our review begins by focusing on cognitive, motivational/affective, and behavioral team processes processes that enable team members to combine their resources to resolve task demands and, in so doing, be effective. We then turn our attention to identifying interventions, or "levers," that can shape or align team processes and thereby provide tools and applications that can improve team effectiveness. Topic specific conclusions and recommendations are given throughout the review. There is a solid foundation for concluding that there is an emerging science of team effectiveness and that findings from this research foundation provide several means to improve team effectiveness. In the concluding section, we summarize our primary findings to highlight specific research, application, and policy recommendations for enhancing the effectiveness of work groups and teams. PMID- 26158913 TI - The Science of Team Effectiveness. PMID- 26158914 TI - Potential predictors of lower extremity impairments in motor coordination of stroke survivors. AB - BACKGROUND: It is well recognized that the negative motor impairments following upper motor neuron damage, e.g., loss of strength and dexterity (motor coordination), mostly contribute to disability. Many factors may predict impairments in motor coordination (MC) and the identifications of these factors could help rehabilitation professionals to select variables to be considered in the evaluation and interventions aimed at improving MC of the lower limbs after stroke. AIM: To investigate the potential predictors of motor coordination (MC) of the paretic lower limb with stroke subjects, as assessed by the Lower Limb Motor Coordination Test (LEMOCOT). DESIGN: Cross-sectional, observational study. SETTING: University laboratory. POPULATION: One hundred and six stroke subjects. METHODS: The selected potential predictors of the LEMOCOT scores were age, gender, motor recovery and sensation of the lower limb, tonus of the knee extensor and plantar flexor muscles, and strength of the hip flexor and knee flexor/extensor muscles. Step-wise multiple regression was employed for analysis. RESULTS: Only motor recovery, tonus of the plantar flexor muscles, and age reached significance (P<0.05) and, consequently, were kept in the model. Motor recovery alone was able to explain 46% (F=89.0, P<0.001) of the variance in the LEMOCOT scores. When tonus of the plantar flexor muscles and age were included in the model, the explained variance increased to 54% (F=42.0, P<0.001). Lower limb motor recovery was positively associated with the LEMOCOT scores, whereas the tonus of the plantar flexor muscles and age were negatively correlated. CONCLUSIONS: Motor recovery of the lower limb, tonus of the plantar flexor muscles, and age were significant predictors of MC of the paretic lower limb. CLINICAL REHABILITATION IMPACT: These findings could help rehabilitation professionals to evaluate MC deficits and plan interventions aimed at improving MC of the lower limbs for stroke subjects, based upon the knowledge of the possible factors that could contribute to MC impairments. PMID- 26158915 TI - EURO-MUSCULUS/USPRM Basic Scanning Protocols for shoulder. AB - In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned shoulder structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers. PMID- 26158916 TI - EURO-MUSCULUS/USPRM Basic Scanning Protocols for elbow. AB - In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned elbow structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers. PMID- 26158917 TI - EURO-MUSCULUS/USPRM Basic Scanning Protocols for wrist and hand. AB - In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned wrist/hand structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers. PMID- 26158918 TI - Virtual reality for stroke rehabilitation: an abridged version of a Cochrane review. AB - Virtual reality and interactive video gaming have emerged as new treatment approaches in stroke rehabilitation settings over the last ten years. The primary objective of this review was to determine the effectiveness of virtual reality on upper limb function and activity after stroke. The impact on secondary outcomes including gait, cognitive function and activities of daily living was also assessed. Randomized and quasi-randomized controlled trials comparing virtual reality with an alternative intervention or no intervention were eligible to be included in the review. The authors searched a number of electronic databases including: the Cochrane Stroke Group Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, clinical trial registers, reference lists, Dissertation Abstracts and contacted key researchers in the field. Search results were independently examined by two review authors to identify studies meeting the inclusion criteria. A total of 37 randomized or quasi randomized controlled trials with a total of 1019 participants were included in the review. Virtual reality was found to be significantly more effective than conventional therapy in improving upper limb function (standardized mean difference [SMD] 0.28, 95% confidence intervals [CI] 0.08 to 0.49) based on 12 studies and significantly more effective than no therapy in improving upper limber function (SMD 0.44 [95% CI 0.15 to 0.73]) based on nine studies. The use of virtual reality also significantly improved activities of daily living function when compared to more conventional therapy approaches (SMD 0.43 [95% CI 0.18 to 0.69]) based on eight studies. While there are a large number of studies assessing the efficacy of virtual reality they tend to be small and many are at risk of bias. While there is evidence to support the use of virtual reality intervention as part of upper limb training programs, more research is required to determine whether it is beneficial in terms of improving lower limb function and gait and cognitive function. PMID- 26158919 TI - Physical rehabilitation for critical illness myopathy and neuropathy: an abridged version of Cochrane Systematic Review. AB - Intensive care unit (ICU) acquired or generalised weakness due to critical illness myopathy (CIM) and polyneuropathy (CIP) are major causes of chronically impaired motor function that can affect activities of daily living and quality of life. Physical rehabilitation of those affected might help to improve activities of daily living. Our primary objective was to assess the effects of physical rehabilitation therapies and interventions for people with CIP and CIM in improving activities of daily living such as walking, bathing, dressing and eating. Secondary objectives were to assess effects on muscle strength and quality of life, and to assess adverse effects of physical rehabilitation. On 16 July 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register and on 14 July 2014 we searched CENTRAL, MEDLINE, EMBASE and CINAHL Plus. In July 2014, we searched the Physiotherapy Evidence Database (PEDro) and three trials registries for ongoing trials and further data about included studies with no language restrictions. We also handsearched relevant conference proceedings and screened reference lists to identify further trials. We planned to include randomised controlled trials (RCTs), quasi-RCTs and randomised controlled cross-over trials of any rehabilitation intervention in people with acquired weakness syndrome due to CIP/CIM. We would have extracted data, assessed the risk of bias and classified the quality of evidence for outcomes in duplicate, according to the standard procedures of The Cochrane Collaboration. Outcome data collection would have been for activities of daily living (for example, mobility, walking, transfers and self care). Secondary outcomes included muscle strength, quality of life and adverse events. The search strategy retrieved 3587 references. After examination of titles and abstracts, we retrieved the full text of 24 potentially relevant studies. None of these studies met the inclusion criteria of our review. No data were suitable to be included in a meta-analysis. There are no published RCTs or quasi-RCTs that examine whether physical rehabilitation interventions improve activities of daily living for people with CIP and CIM. Large RCTs, which are feasible, need to be conducted to explore the role of physical rehabilitation interventions for people with CIP and CIM. This paper is based on a Cochrane Review published in in the Cochrane Database of Systematic Reviews (CDSR) 2015, Issue 3, DOI: 10.1002/14651858.CD010942.pub2. (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the CDSR should be consulted for the most recent version of the review. PMID- 26158920 TI - Exercise for treating patellofemoral pain syndrome: an abridged version of Cochrane systematic review. AB - BACKGROUND: Patellofemoral pain syndrome (PFPS) is a common knee problem characterised by retropatellar or peripatellar pain, which particularly affects adolescents and young adults. Exercise therapy is often prescribed. AIM: To assess the effects of exercise therapy in people with PFPS. DESIGN: Systematic review. SETTING: All settings. POPULATION: Adolescents and adults with PFPS. METHODS: A search was performed in nine databases up to May 2014, including the Cochrane Register, MEDLINE and EMBASE. Randomised and quasi-randomised trials evaluating the effect of exercise therapy in adolescents and adults with PFPS were considered for inclusion. Two review authors independently selected trials, extracted data and assessed risk of bias. RESULTS: In total, 31 trials including 1690 participants were included in this review, of which most were at high risk of performance bias and detection bias due to lack of blinding. The included studies provided evidence for: exercise therapy versus control; exercise therapy versus other conservative interventions (e.g. taping); and different exercises or exercise programmes. Pooled data favoured exercise therapy over control for pain during activity (short term MD -1.46 [-2.39, -0.54]), usual pain (short term estimated MD -1.44 [-2.48,-0.39]), functional ability; (short term estimated MD 12.21 [6.44, 18.09] and long term recovery (RR 1.35 [0.99, 1.84]). Pooled data favoured hip and knee exercise over knee exercises alone for pain during activity (short-term MD -2.20 [3.80, -0.60]) and usual pain (short term MD-1.77 [-2.78, 0.76]). CONCLUSION: This review found very low quality but consistent evidence that exercise therapy for PFPS may result in clinically important reduction in pain and improvement in functional ability, as well as enhancing long-term recovery. There is some very low quality evidence that hip plus knee exercises may be more effective in reducing pain than knee exercise alone. CLINICAL REHABILITATION IMPACT: Very low quality evidence but consistent evidence indicates that exercise therapy benefits patients with PFP. However, there is insufficient evidence to determine the best form of exercise therapy and it is unknown whether this result would apply to all people with PFPS. PMID- 26158921 TI - Balneotherapy (or spa therapy) for rheumatoid arthritis. An abridged version of Cochrane Systematic Review. AB - BACKGROUND: Treatment options for rheumatoid arthritis (RA) include pharmacological interventions, physical therapy treatments and balneotherapy. AIM: To evaluate the benefits and harms of balneotherapy in patients with RA. DESIGN: A systematic review. POPULATION: Studies were eligible if they were randomised controlled trials consisting of participants with definitive or classical RA. METHODS: We searched various databases up to December 2014. Balneotherapy had to be the intervention under study, and had to be compared with another intervention or with no intervention. We considered pain, improvement, disability, tender joints, swollen joints and adverse events among the main outcome measures. We excluded studies when only laboratory variables were reported as outcome measures. Two review authors independently selected trials, performed data extraction and assessed risk of bias. RESULTS: This review includes nine studies involving 579 participants. Most studies showed an unclear risk of bias in most domains. We found no statistically significant differences on pain or improvement between mudpacks versus placebo (1 study; N.=45; hand RA; very low level of evidence). As for the effectiveness of additional radon in carbon dioxide baths, we found no statistically significant differences between groups for all outcomes at three-month follow-up (2 studies; N.=194; low to moderate level of evidence). We noted some benefit of additional radon at six months in pain (moderate level of evidence). One study (N.=148) compared balneotherapy (seated immersion) versus hydrotherapy (exercises in water), land exercises or relaxation therapy. We found no statistically significant differences in pain or in physical disability (very low level of evidence) between groups. We found no statistically significant differences in pain intensity at eight weeks, but some benefit of mineral baths in overall improvement at eight weeks compared to Cyclosporin A (1 study; N.=57; low level of evidence). CONCLUSION: Overall evidence is insufficient to show that balneotherapy is more effective than no treatment; that one type of bath is more effective than another or that one type of bath is more effective than exercise or relaxation therapy. CLINICAL REHABILITATION IMPACT: We were not able to assess any clinical relevant impact of balneotherapy over placebo, no treatment or other treatments. PMID- 26158922 TI - Dynamics of Interstitial Fluid Pressure in Extracellular Matrix Hydrogels in Microfluidic Devices. AB - In order to understand how interstitial fluid pressure and flow affect cell behavior, many studies use microfluidic approaches to apply externally controlled pressures to the boundary of a cell-containing gel. It is generally assumed that the resulting interstitial pressure distribution quickly reaches a steady-state, but this assumption has not been rigorously tested. Here, we demonstrate experimentally and computationally that the interstitial fluid pressure within an extracellular matrix gel in a microfluidic device can, in some cases, react with a long time delay to external loading. Remarkably, the source of this delay is the slight (~100 nm in the cases examined here) distension of the walls of the device under pressure. Finite-element models show that the dynamics of interstitial pressure can be described as an instantaneous jump, followed by axial and transverse diffusion, until the steady pressure distribution is reached. The dynamics follow scaling laws that enable estimation of a gel's poroelastic constants from time-resolved measurements of interstitial fluid pressure. PMID- 26158923 TI - Lady in Red: Hormonal Predictors of Women's Clothing Choices. AB - Recent evidence supports the idea that women use red clothing as a courtship tactic, and results from one study further suggested that women were more likely to wear red on days of high fertility in their menstrual cycles. Subsequent studies provided mixed support for the cycle-phase effect, although all such studies relied on counting methods of cycle-phase estimation and used between subjects designs. By comparison, in the study reported here, we employed frequent hormone sampling to more accurately assess ovulatory timing and used a within subjects design. We found that women were more likely to wear red during the fertile window than on other cycle days. Furthermore, within-subjects fluctuations in the ratio of estradiol to progesterone statistically mediated the within-subjects shifts in red-clothing choices. Our results appear to represent the first direct demonstration of specific hormone measurements predicting observable changes in women's courtship-related behaviors. We also demonstrate the advantages of hormonal determination of ovulatory timing for tests of cycle phase shifts in psychology or behavior. PMID- 26158924 TI - Intra- Versus Intersex Aggression: Testing Theories of Sex Differences Using Aggression Networks. AB - Two theories offer competing explanations of sex differences in aggressive behavior: sexual-selection theory and social-role theory. While each theory has specific strengths and limitations depending on the victim's sex, research hardly differentiates between intrasex and intersex aggression. In the present study, 11,307 students (mean age = 14.96 years; 50% girls, 50% boys) from 597 school classes provided social-network data (aggression and friendship networks) as well as physical (body mass index) and psychosocial (gender and masculinity norms) information. Aggression networks were used to disentangle intra- and intersex aggression, whereas their class-aggregated sex differences were analyzed using contextual predictors derived from sexual-selection and social-role theories. As expected, results revealed that sexual-selection theory predicted male-biased sex differences in intrasex aggression, whereas social-role theory predicted male biased sex differences in intersex aggression. Findings suggest the value of explaining sex differences separately for intra- and intersex aggression with a dual-theory framework covering both evolutionary and normative components. PMID- 26158925 TI - Hydrogel Inlay for Presbyopia: Objective and Subjective Visual Outcomes. AB - PURPOSE: To evaluate changes in visual performance and ocular optical quality after implantation of a corneal hydrogel inlay as a treatment for presbyopia. METHODS: A Raindrop Near Vision Inlay (ReVision Optics, Lake Forest, CA) was implanted monocularly on the stromal bed of a femtosecond laser-assisted generated corneal flap of non-dominant eyes of 22 patients with emmetropic presbyopia (preoperative spherical equivalent range: -0.50 to 1.00 diopters). Efficacy was determined by measuring near and distance visual acuities and ocular aberrations, and satisfaction was assessed by a patient questionnaire. RESULTS: The preoperative monocular uncorrected near visual acuity of the inlay inserted eye was 20/129 +/- 1 Snellen (range: 20/135 to 20/61 Snellen) and improved to 20/35 +/- 2 Snellen (range: 20/61 to 20/20 Snellen) (P < .01) at 6 months postoperatively. The monocular uncorrected distance visual acuity of the eye receiving the inlay was 20/25 +/- 2 Snellen (range: 20/50 to 20/20 Snellen) preoperatively and 20/25 +/- 1 Snellen (range: 20/50 to 20/20 Snellen) at 6 months postoperatively (P =.257). According to the questionnaire responses, 82% of patients were satisfied. This was despite near glasses needs remaining in 13.6% of the cohort and the presence of glare and a decrease in night vision in approximately 40% of patients. The primary spherical aberration coefficient Z4(0) changed from positive to negative values in all patients (P < .01). However, the point spread function showed no significant change. CONCLUSIONS: Hydrogel corneal inlays improve uncorrected near visual acuity in patients with presbyopia with only moderate effect on visual quality. However, the satisfaction with this therapy was relatively lower in these Korean patients than that reported previously in Western patients. PMID- 26158926 TI - Changes in Aqueous Humor pH After Femtosecond Laser-Assisted Cataract Surgery. AB - PURPOSE: To compare aqueous humor pH values in patients during femtosecond laser assisted cataract surgery with patients during conventional phacoemulsification. METHODS: A prospective clinical study was conducted in 29 eyes of 29 patients who underwent cataract surgery by a single surgeon. The femtosecond laser group included 15 eyes operated on with a femtosecond laser platform (Catalys; Abbott Medical Optics, Santa Ana, CA) and the phacoemulsification group included 14 eyes that were operated on with conventional phacoemulsification. The femtosecond laser group was subdivided into low, medium, and high level of cavitation gas bubbles after docking and the femtosecond laser procedure, according to the judgment of the surgeon. Aqueous humor samples (0.10 to 0.15 mL) were collected through a paracentesis from each patient after docking, corneal incisions, and nucleus fragmentation in the femtosecond laser group and after corneal incisions but before injection of viscoelastic in the phacoemulsification group, then analyzed with a pH meter. RESULTS: The mean pH was 6.53 +/- 0.09 (range: 6.42 to 6.70) and 7.42 +/- 0.07 (range: 7.28 to 7.48) in the femtosecond laser and phacoemulsification groups, respectively (P < .001). In the femtosecond laser group, no significant differences in pH were observed between the three subgroups after docking and the femtosecond laser surgical procedure: low (6.55 +/- 0.09 [range: 6.53 to 6.57]), medium (6.54 +/- 0.07 [range: 6.52 to 6.55]), and high (6.42 +/- 0.00 [range: 6.40 to 6.44]) level of gas bubbles. CONCLUSIONS: Cavitation bubbles derived from the photodisruption process in femtosecond laser assisted cataract surgery lead to an acidic shift of the aqueous humor pH as a result of the transformation of carbon dioxide to carbonic acid. The level of gas bubbles visible after the laser photodisruption does not seem to correlate with this pH shift. Further analysis of femtosecond laser-assisted cataract surgery is necessary. PMID- 26158927 TI - Prospective Randomized Intraindividual Comparison of Posterior Capsule Opacification After Implantation of an IOL With and Without Heparin Surface Modification. AB - PURPOSE: To compare posterior capsule opacification (PCO) of a hydrophobic acrylic heparin surface modified intraocular lens (HSM-IOL) and an uncoated IOL (UC-IOL) 1 year after implantation. METHODS: One hundred two eyes of 51 patients underwent routine phacoemulsification with randomized implantation of a HSM-IOL in one eye (the HSM-IOL group) and a UC-IOL in the fellow eye (the UC-IOL group). Morphologic PCO evaluation was performed comparing digital photographs in retroillumination using the Evaluation of Posterior Capsule Opacification (EPCO) system, grading the density of the opacification from 0 to 4 (0 = none, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe). Distance visual acuities, subjective manifest refraction, pupil size, straylight measurements, flare in the anterior chamber using a laser flare meter, and contrast sensitivity were also evaluated. RESULTS: The mean total EPCO score was slightly higher in the HSM-IOL group (0.50 +/- 0.45) compared to the UC-IOL group (0.45 +/- 0.46), but did not reach statistical significance. No statistically significant differences were found in the other main outcome parameters (straylight measurement, distance visual acuities, flare in the anterior chamber, and mesopic and photopic contrast sensitivity) when comparing both IOLs. CONCLUSION: Although the HSM-IOL showed decreased flare 1 day postoperatively, no statistically significant differences regarding PCO were found 1 year postoperatively. PMID- 26158928 TI - Femtosecond Laser-Assisted Intrastromal Relaxing Incisions After Penetrating Keratoplasty: Effect of Incision Depth. AB - PURPOSE: To correlate the efficacy of femtosecond laser-assisted intrastromal relaxing incisions after penetrating keratoplasty with the posterior depth of corneal incisions. METHODS: Twenty eyes of 20 patients were treated for regular postoperative penetrating keratoplasty astigmatism. Sutures had been removed and refraction had stabilized. Ultrasound pachymetry was used to calculate incisional depth. Femtosecond laser-assisted paired arcuate incisions were made inside the graft stroma, leaving 90 um of intact anterior cornea including epithelium. The intact posterior corneal margin was 10% of the measured corneal thickness for 10 patients (10% group) and 125 um for the remaining 10 patients (125-um group). Follow-up visits consisted of biomicroscopy, intraocular pressure measurement, fundus examination, and topographic evaluation using anterior segment optical coherence tomography at 1 and 3 months. Postoperative corneal thickness and the depth of incisions were measured with optical coherence tomography. RESULTS: Corrected distance visual acuity improved from 0.5 to 0.3 logMAR (Snellen: 20/63 to 20/40, P < .05) in the 10% group and remained constant in the 125-um group. The refractive cylinder decreased by 34% in the 10% group (range: 0% to 60%), but did not change in the 125-um group. The topographic anterior cylinder decreased in both groups by 48% (range: 0% to 67%) and 13% (range: 0% to 38%), respectively. The smaller the posterior intact corneal margin, the higher the surgically induced astigmatism (P < .05). CONCLUSIONS: Efficacy of femtosecond laser-assisted intrastromal relaxing incisions is correlated with the posterior depth of the incisions. The deeper incisions were more effective. PMID- 26158929 TI - Biomechanical Modeling of Femtosecond Laser Keyhole endokeratophakia Surgery. AB - PURPOSE: To apply a finite element model to endokeratophakia and evaluate anterior and posterior corneal surface changes. METHODS: Spatial elevation data (Pentacam HR; Oculus, Wetzlar, Germany) were obtained for the front and back corneal surfaces of an eye prior to undergoing an endokeratophakia procedure. These were used to warp a spherical template finite element model of the cornea to create a patient-specific finite element mesh and the initial stress distribution was computed with an iterative approach. The finite element model (Optimeyes; Integrated Scientific Services, Biel, Switzerland) included non linear elastic characteristics of the stroma. The endokeratophakia procedure was recreated in the model: a donor lenticule (-10.50 diopters [D], 5.75-mm zone, 127 um thick) was inserted into a lamellar pocket (180-um deep, 6.25-mm diameter) and two 2-mm small incisions were made at 150 degrees and 330 degrees . Anterior and posterior surfaces, computed by the finite element model, were compared to clinical data to assess accuracy and reliability of finite element modeling. RESULTS: The postoperative axial curvature produced by the model closely resembled the patient data; average curvature was 48.01 D clinically and 48.23 D in the simulation, and corneal astigmatism was 3.01 D clinically and 2.88 D in the simulation. The posterior best-fit sphere elevation map also matched the patient data, replicating inward bulging of the posterior surface by approximately 40 um. Stress distribution modeling predicted a stress increase by 159.94% +/- 73% in the cap and a stress decrease by 32.41% +/- 21% in the stromal bed. CONCLUSIONS: Finite element modeling of the cornea reproduced the clinically observed anterior and posterior corneal surface changes following an endokeratophakia procedure. This case sets the stage for further study to refine and yield predictive finite element modeling for the evaluation of corneal refractive surgical procedures. PMID- 26158930 TI - A Modified Glued Transscleral Intraocular Lens Implantation: Suture-Assisted Sutureless Technique. AB - PURPOSE: To report a modified surgical technique as an alternative procedure for sutureless fibrin glue-assisted Transscleral intraocular lens (IOL) fixation. METHODS: Description of the modified surgical technique with an accompanying video. RESULTS: In the standard glued IOL fixation technique, the leading haptic is externalized using a forceps through the sclerotomy and an assistant holds the haptic while the second IOL haptic is bimanually externalized, using the handshake technique, through the other sclerotomy site. In the author's technique, called the suture-assisted sutureless technique, IOL haptics were tied with a looped 9-0 polypropylene suture with an attached curved needle. The suture needle was fastened to the haptic, passed through the sclerotomy site, and pulled out to externalize the haptic through the sclerotomy site. CONCLUSIONS: This technique is an easy, feasible, and assistant-free procedure for glued IOL implantation in aphakic eyes. PMID- 26158931 TI - Peep Into Visual Acuity Chart Through an Opening: A New Concept of Binocular Open view Visual Acuity Test. PMID- 26158932 TI - The Dynamic Safety for Cross-Linking in Thin Corneas With Extra Protection Under a Contact Lens. PMID- 26158933 TI - Morality: An Evolutionary Account. AB - Refinements in Darwin's theory of the origin of a moral sense create a framework equipped to organize and integrate contemporary theory and research on morality. Morality originated in deferential, cooperative, and altruistic "social instincts," or decision-making strategies, that enabled early humans to maximize their gains from social living and resolve their conflicts of interest in adaptive ways. Moral judgments, moral norms, and conscience originated from strategic interactions among members of groups who experienced confluences and conflicts of interest. Moral argumentation buttressed by moral reasoning is equipped to generate universal and impartial moral standards. Moral beliefs and standards are products of automatic and controlled information-processing and decision-making mechanisms. To understand how people make moral decisions, we must understand how early evolved mechanisms in the old brain and recently evolved mechanisms in the new brain are activated and how they interact. Understanding what a sense of morality is for helps us understand what it is. PMID- 26158934 TI - The Function of Fiction is the Abstraction and Simulation of Social Experience. AB - Fiction literature has largely been ignored by psychology researchers because its only function seems to be entertainment, with no connection to empirical validity. We argue that literary narratives have a more important purpose. They offer models or simulations of the social world via abstraction, simplification, and compression. Narrative fiction also creates a deep and immersive simulative experience of social interactions for readers. This simulation facilitates the communication and understanding of social information and makes it more compelling, achieving a form of learning through experience. Engaging in the simulative experiences of fiction literature can facilitate the understanding of others who are different from ourselves and can augment our capacity for empathy and social inference. PMID- 26158935 TI - A Blueprint for Social Cognitive Development. AB - The field of social cognitive development (SCD) has historically failed to emerge as a dominant approach in developmental psychology. We take this opportunity to articulate the assumptions, goals, and contributions of SCD with the aim of invigorating research from this perspective. We begin by describing the current landscape of social and cognitive development, suggesting what they have and have not given us. We then outline major goals of the social cognitive developmental approach and walk through examples of successful SCD research. Finally, we examine the unique potential of the social cognitive approach to cross-fertilize social and cognitive development (as well as related fields such as social psychology and neuroscience) and to answer new questions about development. PMID- 26158936 TI - A Comparison of Models for Interstate Wars and for Individual Violence. AB - It is assumed that violence is functional at both individual and societal levels. A model developed for violent individuals is compared with a proposed model for interstate wars. In both domains, the data are consistent with the assumption that violence is functional. At the societal level, the contingencies of training are provided by official staff and require reasonably well-socialized soldiers. At the individual level, reinforcers are provided by victims, and aggressors are usually socially incompetent. In the societal model, decision makers receive rein forcers for initiating and winning wars. The combat soldiers' behavior is somewhat paradoxical. Soldiers are thought to remain in harm's way out of love for their buddies. The actual reinforcers for their combat behavior are unknown. PMID- 26158937 TI - Hedonomics: Bridging Decision Research With Happiness Research. AB - One way to increase happiness is to increase the objective levels of external outcomes; another is to improve the presentation and choices among external outcomes without increasing their objective levels. Economists focus on the first method. We advocate the second, which we call hedonomics. Hedonomics studies (a) relationships between presentations (how a given set of out-comes are arranged among themselves or relative to other outcomes) and happiness and (b) relationships between choice (which option among alternative options one chooses) and happiness. PMID- 26158938 TI - Relating Psychology and Neuroscience: Taking Up the Challenges. AB - Advances in brain research have invigorated an ongoing debate about the relations between psychology and neuroscience. Cognitive science has historically neglected the study of neuroscience, although the influential subfield of cognitive neuroscience has since attempted to combine information processing approaches with an awareness of brain functioning. Although cognitive neuroscience does not necessarily support a reductionist approach, certain philosophers of mind have suggested that psychological constructs will eventually be replaced with descriptions of neurobiological processes. One implicitly popular response to this proposal is that neuroscience represents a level of implementation that is separate from a level of cognition. Although recent work in the philosophy of mind has gone some way to explicating the concept of psychological and neuroscience approaches as different levels, it is suggested here that a tidy framework of levels is somewhat tenuous. A particular challenge comes from the metatheoretical position of embodiment, which places the mind within the body and brain of an active organism which is deeply embedded in the world. In providing an integration of brain, body, mind, and culture, embodiment exemplifies an important line of defense against claims of the possible reduction of psychology by neuroscience. PMID- 26158939 TI - A New Solution to the Recovered Memory Debate. AB - The controversy regarding recovered memories of childhood sexual abuse (CSA) has been characterized by two perspectives. According to one perspective, some people repress their memories of abuse because these experiences have been so emotionally traumatic, and they become capable of recalling the CSA only when it is psychologically safe to do so many years later. According to the other perspective, many reports of recovered memories of sexual abuse are false memories, often inadvertently fostered by therapists. In this article, we provide evidence for a third interpretation that applies to a subset of people reporting recollections of CSA; it does not require the concepts of repression, trauma, or false memory. These people did not experience their CSA as traumatic; they either failed to think about their abuse for years or forgot their previous recollections, and they recalled their CSA spontaneously after encountering reminders outside of psychotherapy. Their recovered memories are corroborated at the same rate as those of people who never forgot their abuse. Hence, recalling CSA after many years is not the same thing as having recalled a previously repressed memory of trauma. PMID- 26158940 TI - The Consequences of False Memories for Food Preferences and Choices. AB - False memories, or memories for events that never occurred, have been documented in the real world and in the laboratory. In the real world, false memories involving trauma and abuse have resulted in real-life consequences. In the laboratory, researchers have just begun to study the consequences of false memories. We review this laboratory-based work and show how false memories for food-related experiences (e.g., becoming ill after eating egg salad) can lead to attitudinal and behavioral consequences (e.g., lowered self-reported preference for and decreased consumption of egg salad). PMID- 26158941 TI - Parental Divorce and Children's Adjustment. AB - This article reviews the research literature on links between parental divorce and children's short-term and long-term adjustment. First, I consider evidence regarding how divorce relates to children's externalizing behaviors, internalizing problems, academic achievement, and social relationships. Second, I examine timing of the divorce, demographic characteristics, children's adjustment prior to the divorce, and stigmatization as moderators of the links between divorce and children's adjustment. Third, I examine income, interparental conflict, parenting, and parents well-being as mediators of relations between divorce and children's adjustment. Fourth, I note the caveats and limitations of the research literature. Finally, I consider notable policies related to grounds for divorce, child support, and child custody in light of how they might affect children s adjustment to their parents divorce. PMID- 26158942 TI - The Utility and Ubiquity of Taboo Words. AB - Taboo words are defined and sanctioned by institutions of power (e.g., religion, media), and prohibitions are reiterated in child-rearing practices. Native speakers acquire folk knowledge of taboo words, but it lacks the complexity that psychological science requires for an understanding of swearing. Misperceptions persist in psychological science and in society at large about how frequently people swear or what it means when they do. Public recordings of taboo words establish the commonplace occurrence of swearing (ubiquity), although frequency data are not always appreciated in laboratory research. A set of 10 words that has remained stable over the past 20 years accounts for 80% of public swearing. Swearing is positively correlated with extraversion and Type A hostility but negatively correlated with agreeableness, conscientiousness, religiosity, and sexual anxiety. The uniquely human facility for swearing evolved and persists because taboo words can communicate emotion information (anger, frustration) more readily than nontaboo words, allowing speakers to achieve a variety of personal and social goals with them (utility). A neuro-psycho-social framework is offered to unify taboo word research. Suggestions for future research are offered. PMID- 26158943 TI - Impulse and Self-Control From a Dual-Systems Perspective. AB - Though human beings embody a unique ability for planned behavior, they also often act impulsively. This insight may be important for the study of self-control situations in which people are torn between their long-term goals to restrain behavior and their immediate impulses that promise hedonic fulfillment. In the present article, we outline a dual-systems perspective of impulse and self control and suggest a framework for the prediction of self-control outcomes. This framework combines three elements that, considered jointly, may enable a more precise prediction of self-control outcomes than they do when studied in isolation: impulsive precursors of behavior, reflective precursors, and situational or dispositional boundary conditions. The theoretical and practical utility of such an approach is demonstrated by drawing on recent evidence from several domains of self-control such as eating, drinking, and sexual behavior. PMID- 26158944 TI - Investigating the Awareness of Remembering. AB - There is a marked lack of consensus concerning the best way to learn how conscious experiences arise. In this article, we advocate for scientific approaches that attempt to bring together four types of phenomena and their corresponding theoretical accounts: behavioral acts, cognitive events, neural events, and subjective experience. We propose that the key challenge is to comprehensively specify the relationships among these four facets of the problem of understanding consciousness without excluding any facet. Although other perspectives on consciousness can also be informative, combining these four perspectives could lead to significant progress in explaining a conscious experience such as remembering. We summarize some relevant findings from cognitive neuroscience investigations of the conscious experience of memory retrieval and of memory behaviors that transpire in the absence of the awareness of remembering. These examples illustrate suitable scientific strategies for making progress in understanding consciousness by developing and testing theories that connect the behavioral expression of recall and recognition, the requisite cognitive transactions, the neural events that make remembering possible, and the awareness of remembering. PMID- 26158945 TI - The Origins of Face Processing in Humans: Phylogeny and Ontogeny. AB - Faces are crucial for nonverbal communication in humans and related species. From the first moments of life, newborn infants prefer to look at human faces over almost any other form of stimuli. Since this finding was first observed, there has been much debate regarding the "special" nature of face processing. Researchers have put forward numerous developmental models that attempt to account for this early preference and subsequent maturation of the face processing system. In this article, we review these models and their supporting evidence drawing on literature from developmental, evolutionary, and comparative psychology. We conclude that converging data from these fields strongly suggests that face processing is conducted by a dedicated and complex neural system, is not human specific, and is unlikely to have emerged recently in evolutionary history. PMID- 26158946 TI - Unlocking the Energy Dynamics of Executive Functioning: Linking Executive Functioning to Brain Glycogen. AB - Past work suggests that executive functioning relies on glucose as a depletable energy, such that executive functioning uses a relatively large amount of glucose and is impaired when glucose is low. Glucose from the bloodstream is one energy source for the brain, and glucose stored in the brain as glycogen is another. A review of the literature on glycogen suggests that executive functioning uses it in much the same way as glucose, such that executive functioning uses glycogen and is impaired when glycogen is low. Findings on stress, physical persistence, glucose tolerance, diabetes, sleep, heat, and other topics provide general support for this view. PMID- 26158947 TI - Development, Freedom, and Rising Happiness: A Global Perspective (1981-2007). AB - Until recently, it was widely held that happiness fluctuates around set points, so that neither individuals nor societies can lastingly increase their happiness. Even though recent research showed that some individuals move enduringly above or below their set points, this does not refute the idea that the happiness levels of entire societies remain fixed. Our article, however, challenges this idea: Data from representative national surveys carried out from 1981 to 2007 show that happiness rose in 45 of the 52 countries for which substantial time-series data were available. Regression analyses suggest that that the extent to which a society allows free choice has a major impact on happiness. Since 1981, economic development, democratization, and increasing social tolerance have increased the extent to which people perceive that they have free choice, which in turn has led to higher levels of happiness around the world, as the human development model suggests. PMID- 26158948 TI - Replication and p Intervals: p Values Predict the Future Only Vaguely, but Confidence Intervals Do Much Better. AB - Replication is fundamental to science, so statistical analysis should give information about replication. Because p values dominate statistical analysis in psychology, it is important to ask what p says about replication. The answer to this question is "Surprisingly little." In one simulation of 25 repetitions of a typical experiment, p varied from <.001 to .76, thus illustrating that p is a very unreliable measure. This article shows that, if an initial experiment results in two-tailed p = .05, there is an 80% chance the one-tailed p value from a replication will fall in the interval (.00008, .44), a 10% chance that p <.00008, and fully a 10% chance that p >.44. Remarkably, the interval-termed a p interval-is this wide however large the sample size. p is so unreliable and gives such dramatically vague information that it is a poor basis for inference. Confidence intervals, however, give much better information about replication. Researchers should minimize the role of p by using confidence intervals and model fitting techniques and by adopting meta-analytic thinking. PMID- 26158949 TI - Identifying Systematic Disobedience in Milgram's Obedience Experiments: A Meta Analytic Review. AB - A meta-analysis of data from eight of Mil-gram's obedience experiments reveals previously undocumented systematicity in the behavior of disobedient participants. In all studies, disobedience was most likely at 150 v, the point at which the shocked "learner" first requested to be released. Further illustrating the importance of the 150-v point, obedience rates across studies covaried with rates of disobedience at 150 v, but not at any other point; as obedience decreased, disobedience at 150 v increased. In contrast, disobedience was not associated with the learner's escalating expressions of pain. This analysis identifies a critical decision point in the obedience paradigm and suggests that disobedient participants perceived the learner's right to terminate the experiment as overriding the experimenter's orders, a finding with potential implications for the treatment of prisoners. PMID- 26158950 TI - Cognitive Conceptualism-Where Have All the Affects Gone? Additional Corrections for Barrett et al. (2007). AB - Barrett et al. (2007) claim that their approach to emotions covers more of the available evidence than does my affective neuroscience approach (Panksepp, 2007b). In fact, the weight of neurological evidence indicates that raw affect, as monitored by many behavioral tasks, is an aspect of the arousal of instinctual emotional networks. This provides an empirical approach to understanding how primary-process emotional feelings are constituted by neural activities (Panksepp, 2008). There is abundant evidence for the existence of a variety of primal emotions shared across mammalian species that are biologically ingrained tools for living and learning and that may allow higher brain regions to conceptualize what is really important in the world. Barrett et al., misrepresent my views; an accurate depiction of them can be found in this article and in Gallagher (2008). Abundant cross-species evidence of basic affective systems exists to enrich cognitive-conceptual and attributional theories of human emotions. PMID- 26158951 TI - What Do Sex, Twins, Spotted Hyenas, ADHD, and Sexual Orientation Have in Common? AB - The otoacoustic emissions (OAEs) measured in a collection of special populations of humans and certain nonhuman species suggest that OAEs may provide a window into some processes of human prenatal development and sexual differentiation. For reasons that are unclear, OAEs appear to be highly sensitive to events occurring during prenatal development that seem to be related to the degree of exposure to androgens a fetus receives. The (largely circumstantial) evidence for a relationship between androgen exposure and OAE strength comes from a series of studies of twins, children with attention-deficit/hyperactivity disorder, people of differing sexual orientations, and spotted hyenas, among others. Some conclusions are bolstered by parallel studies using auditory evoked potentials (AEPs). OAEs and AEPs are simple, objective, noninvasive measures that appear to have potential as tools of value to researchers working on a wide variety of basic and applied topics beyond audition. PMID- 26158952 TI - Harnessing Our Inner Angels and Demons: What We Have Learned About Want/Should Conflicts and How That Knowledge Can Help Us Reduce Short-Sighted Decision Making. AB - Although observers of human behavior have long been aware that people regularly struggle with internal conflict when deciding whether to behave responsibly or indulge in impulsivity, psychologists and economists did not begin to empirically investigate this type of want/should conflict until recently. In this article, we review and synthesize the latest research on want/should conflict, focusing our attention on the findings from an empirical literature on the topic that has blossomed over the last 15 years. We then turn to a discussion of how individuals and policy makers can use what has been learned about want/should conflict to help decision makers select far-sighted options. PMID- 26158954 TI - A Theory of the Emergence, Persistence, and Expression of Geographic Variation in Psychological Characteristics. AB - Volumes of research show that people in different geographic regions differ psychologically. Most of that work converges on the conclusion that there are geographic differences in personality and values, but little attention has been paid to developing an integrative account of how those differences emerge, persist, and become expressed at the geographic level. Drawing from research in psychology and other social sciences, we present a theoretical account of the mechanisms through which geographic variation in psychological characteristics emerge and persist within regions, and we propose a model for conceptualizing the processes through which such characteristics become expressed in geographic social indicators. The proposed processes were examined in the context of theory and research on personality traits. Hypotheses derived from the model were tested using personality data from over half a million U.S. residents. Results provided preliminary support for the model, revealing clear patterns of regional variation across the U.S. and strong relationships between state-level personality and geographic indicators of crime, social capital, religiosity, political values, employment, and health. Overall, this work highlights the potential insights generated by including macrolevel perspectives within psychology and suggests new routes to bridging theory and research across several disciplines in the social sciences. PMID- 26158955 TI - Explaining Away: A Model of Affective Adaptation. AB - We propose a model of affective adaptation, the processes whereby affective responses weaken after one or more exposures to emotional events. Drawing on previous research, our approach, represented by the acronym AREA, holds that people attend to self-relevant, unexplained events, react emotionally to these events, explain or reach an understanding of the events, and thereby adapt to the events (i.e., they attend less and have weaker emotional reactions to them). We report tests of new predictions about people's reactions to pleasurable events and discuss the implications of the model for how people cope with negative events, experience emotion in different cultures, and other topics. PMID- 26158953 TI - Analysis of Germline Stem Cell Differentiation Following Loss of GLP-1 Notch Activity in Caenorhabditis elegans. AB - Stem cells generate the differentiated progeny cells of adult tissues. Stem cells in the Caenorhabditis elegans hermaphrodite germline are maintained within a proliferative zone of ~230 cells, ~20 cell diameters in length, through GLP-1 Notch signaling. The distal tip cell caps the germline and supplies GLP-1 activating ligand, and the distal-most germ cells that occupy this niche are likely self-renewing stem cells with active GLP-1 signaling. As germ cells are displaced from the niche, GLP-1 activity likely decreases, yet mitotically cycling germ cells are found throughout the proliferative zone prior to overt meiotic differentiation. Following loss of GLP-1 activity, it remains unclear whether stem cells undergo transit-amplifying (TA) divisions or more directly enter meiosis. To distinguish between these possibilities we employed a temperature-sensitive (ts) glp-1 mutant to manipulate GLP-1 activity. We characterized proliferative zone dynamics in glp-1(ts) mutants at permissive temperature and then analyzed the kinetics of meiotic entry of proliferative zone cells after loss of GLP-1. We found that entry of proliferative zone cells into meiosis following loss of GLP-1 activity is largely synchronous and independent of their distal-proximal position. Furthermore, the majority of cells complete only a single mitotic division before entering meiosis, independent of their distal-proximal position. We conclude that germ cells do not undergo TA divisions following loss of GLP-1 activity. We present a model for the dynamics of the proliferative zone that utilizes cell cycle rate and proliferative zone size and output and incorporates the more direct meiotic differentiation of germ cells following loss of GLP-1 activity. PMID- 26158956 TI - Television Viewing and Aggression: Some Alternative Perspectives. AB - The focus of this article is on the examination of variables that moderate the influence of exposure to TV violence. The research on the relationship between TV violence and aggressive behavior of the audience has largely focused on addressing the social policy issue of whether witnessing TV violence fosters aggressive behavior in viewers, particularly children. There has been a dearth of research addressing the conditions that enhance the aggression stimulating effects of media violence, those that mitigate these effects, and those that may even result in reduced aggression after one witnesses media violence. To illustrate the importance of potential moderating factors, we present longitudinal correlational data relating the degree of viewing TV violence to various social behaviors and cognitive attributes of White and African-American male and female elementary-school-age children. Although TV violence viewing was associated with lower cognitive attributes and negative social behaviors in White males and females and African-American females, a very different pattern of relationships was found for African-American males. PMID- 26158957 TI - Familiarity Breeds Attempts: A Critical Review of Dual-Process Theories of Recognition. AB - Recognition memory and recall/recollection are the major divisions of the psychology of human memory. Theories of recognition have shifted from a "strength" approach to a dual-process view, which distinguishes between knowing that one has experienced an object before and knowing what it was. In this article, I discuss the history of this approach and the two processes of familiarity and recollection and locate their origin in pattern matching and organization. I evaluate various theories in terms of their basic requirements and their defining research and propose the extension of the original two process theory to domains such as pictorial recognition. Finally, I present the main phenomena that a dual-process theory of recognition must account for and discuss future needs and directions of research and development. PMID- 26158958 TI - Rethinking Rumination. AB - The response styles theory (Nolen-Hoeksema, 1991) was proposed to explain the insidious relationship between rumination and depression. We review the aspects of the response styles theory that have been well-supported, including evidence that rumination exacerbates depression, enhances negative thinking, impairs problem solving, interferes with instrumental behavior, and erodes social support. Next, we address contradictory and new findings. Specifically, rumination appears to more consistently predict the onset of depression rather than the duration, but rumination interacts with negative cognitive styles to predict the duration of depressive symptoms. Contrary to original predictions, the use of positive distractions has not consistently been correlated with lower levels of depressive symptoms in correlational studies, although dozens of experimental studies show positive distractions relieve depressed mood. Further, evidence now suggests that rumination is associated with psychopathologies in addition to depression, including anxiety, binge eating, binge drinking, and self harm. We discuss the relationships between rumination and worry and between rumination and other coping or emotion-regulation strategies. Finally, we highlight recent research on the distinction between rumination and more adaptive forms of self-reflection, on basic cognitive deficits or biases in rumination, on its neural and genetic correlates, and on possible interventions to combat rumination. PMID- 26158959 TI - The Founding of the Association for Psychological Science: Part 1. Dialectical Tensions Within Organized Psychology. AB - The founding of the Association for Psychological Science (APS) did not represent the first time a group of psychologists broke away from the American Psychological Association, the parent association of organized psychology in the United States. In fact, the history of organized psychology is replete with examples of splinter groups that sought to better represent the needs and interests of their specific constituencies. All of these breakaway efforts have occurred amid intradisciplinary tensions-the continual push and pull between unity on the one hand and autonomy on the other-that reflect some of the enduring challenges of the field. A historical examination of this dialectic provides a useful framework within which to understand the founding of the APS, its most recent instantiation. PMID- 26158960 TI - The Founding of the Association for Psychological Science: Part 2. The Tipping Point and Early Years. AB - The founding of the Association for Psychological Science (APS) occurred in the context of longstanding dialectical tensions within organized psychology. It represents the most recent breakaway effort from the American Psychological Association (APA), psychology's parent association in the United States. Beginning in the 1970s, numerous APA committees deliberated the Association's structure, making recommendations designed to appease the various constituencies within the changing organization; all but the last of these proposals were ultimately rejected by the APA Council. In 1987, the Assembly for Scientific and Applied Psychologists (ASAP) formed to encourage APA reorganization, and in early 1988, the APA Council approved a reorganization plan; that plan was, however, rejected by the membership. In August 1988, the ASAP became the APS. The early years of the APS were shaped by challenges and successes that would lay the groundwork for the APS to become a prominent organization in the promotion of scientific psychology. An understanding of these events may provide insight into the nature of organized psychology and its future. PMID- 26158961 TI - Understanding the Links Between Social Support and Physical Health: A Life-Span Perspective With Emphasis on the Separability of Perceived and Received Support. AB - Social support has been reliably related to physical health outcomes. However, the conceptual basis of such links needs greater development. In this article, I argue for a life-span perspective on social support and health that takes into account distinct antecedent processes and mechanisms that are related to measures of support over time. Such a view highlights the need to distinguish measures of perceived and received support and its links to more specific diseases (e.g., chronic, acute) and stages of disease development (e.g., incidence). I discuss both the novel implications of these theoretical arguments for research on social support and physical health, as well as the potential intervention approaches that are apparent from this perspective. PMID- 26158963 TI - Editor's Introduction to Vul et al. (2009) and Comments. PMID- 26158962 TI - Patterns of Thinking in Militant Extremism. AB - Recurrent features of the thinking pattern (or mind-set) of violent militant extremists are delineated, discussed, and related to previous research and theory. We examined extremist groups from a diverse range of continents, cultures, and political and religious orientations. We compared statements by (and, to some degree, statements about) these groups and formulated 16 themes common to the militant-extremist mind-set. Among these themes are perceptions of a crisis involving violations of posited sacred values, along with justifications for the use of violence to remediate such problems. There are indications that such themes are not infrequent in the general population. For example, research participants failed to strongly disassociate themselves from the sentiments and framings found in the fanatical items, which undercuts the notion that militant extremist thinking represents bizarre ideation. Militant-extremist thinking appears to represent a major, aggressive form of fanaticism affected by both dispositional and situational factors. Key themes in this thinking pattern might fit together to construct a potentially compelling narrative, which may be a key part of the ideological appeal of salient militant-extremist groups. PMID- 26158964 TI - Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition. AB - Functional magnetic resonance imaging (fMRI) studiesofemotion, personality, and social cognition have drawn much attention in recent years, with high-profile studies frequently reporting extremely high (e.g., >.8) correlations between brain activation and personality measures. We show that these correlations are higher than should be expected given the (evidently limited) reliability of both fMRI and personality measures. The high correlations are all the more puzzling because method sections rarely contain much detail about how the correlations were obtained. We surveyed authors of 55 articles that reported findings of this kind to determine a few details on how these correlations were computed. More than half acknowledged using a strategy that computes separate correlations for individual voxels and reports means of only those voxels exceeding chosen thresholds. We show how this nonindependent analysis inflates correlations while yielding reassuring-looking scattergrams. This analysis technique was used to obtain the vast majority of the implausibly high correlations in our survey sample. In addition, we argue that, in some cases, other analysis problems likely created entirely spurious correlations. We outline how the data from these studies could be reanalyzed with unbiased methods to provide accurate estimates of the correlations in question and urge authors to perform such reanalyses. The underlying problems described here appear to be common in fMRI research of many kinds-not just in studies of emotion, personality, and social cognition. PMID- 26158965 TI - Commentary on Vul et al.'s (2009) "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition". AB - The article "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition" (Vul, Harris, Winkielman, & Pashler, 2009, this issue) makes a broad case that current practice in neuroimaging methodology is deficient. Vul et al. go so far as to demand that authors retract or restate results, which we find wrongly casts suspicion on the confirmatory inference methods that form the foundation of neuroimaging statistics. We contend the authors' argument is overstated and that their work can be distilled down to two points already familiar to the neuroimaging community: that the multiple testing problem must be accounted for, and that reporting of methods and results should be improved. We also illuminate their concerns with standard statistical concepts such as the distinction between estimation and inference and between confirmatory and post hoc inferences, which makes their findings less puzzling. PMID- 26158966 TI - Big Correlations in Little Studies: Inflated fMRI Correlations Reflect Low Statistical Power-Commentary on Vul et al. (2009). AB - Vul, Harris, Winkielman, and Pashler (2009), (this issue) argue that correlations in many cognitive neuroscience studies are grossly inflated due to a widespread tendency to use nonindependent analyses. In this article, I argue that Vul et al.'s primary conclusion is correct, but for different reasons than they suggest. I demonstrate that the primary cause of grossly inflated correlations in whole brain fMRI analyses is not nonindependence, but the pernicious combination of small sample sizes and stringent alpha-correction levels. Far from defusing Vul et al.'s conclusions, the simulations presented suggest that the level of inflation may be even worse than Vul et al.'s empirical analysis would suggest. PMID- 26158967 TI - Correlations in Social Neuroscience Aren't Voodoo: Commentary on Vul et al. (2009). AB - Vul, Harris, Winkielman, and Pashler (2009), (this issue) claim that many brain personality correlations in fMRI studies are "likely ... spurious" (p. 274), and "should not be believed" (p. 285). Several of their conclusions are incorrect. First, they incorrectly claim that whole-brain regressions use an invalid and "nonindependent" two-step inferential procedure, a determination based on a survey sent to researchers that only included nondiagnostic questions about the descriptive process of plotting one's data. We explain how whole-brain regressions are a valid single-step method of identifying brain regions that have reliable correlations with individual difference measures. Second, they claim that large correlations from whole-brain regression analyses may be the result of noise alone. We provide a simulation to demonstrate that typical fMRI sample sizes will only rarely produce large correlations in the absence of any true effect. Third, they claim that the reported correlations are inflated to the point of being "implausibly high." Though biased post hoc correlation estimates are a well-known consequence of conducting multiple tests, Vul et al. make inaccurate assumptions when estimating the theoretical ceiling of such correlations. Moreover, their own "meta-analysis suggests that the magnitude of the bias is approximately .12-a rather modest bias. PMID- 26158968 TI - Discussion of "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition" by Vul et al. (2009). AB - In their article, Vul, Harris, Winkielman, and Pashler (2009), (this issue) raise the issue of nonindependent analysis in behavioral neuroimaging, whereby correlations are artificially inflated as a result of spurious statistical procedures. In this comment, I note that the phenomenon in question is a type of selection bias and hence is neither new nor unique to fMRI. The use of massive, complex data sets (common in modern applications) to answer increasingly intricate scientific questions presents many potential pitfalls to valid statistical analysis. Strong collaboration between statisticians and scientists and the development of statistical methods specific to the types of data encountered in practice can help researchers avoid these pitfalls. PMID- 26158969 TI - Correlations and Multiple Comparisons in Functional Imaging: A Statistical Perspective (Commentary on Vul et al., 2009). AB - Vul, Harris, Winkielman, and Pashler (2009), this issue) claim in their article that the correlations reported in fMRI studies are commonly overstated because researchers tend to report only the highest correlations or only those correlations that exceed some threshold. Their article has in a short time given rise to a spirited debate about key statistical issues at the heart of most functional neuroimaging studies. The debate provides a useful opportunity to discuss core statistical issues in neuroimaging and ultimately provides a chance for the field to grow and move forward. This commentary approaches the debate from a fundamentally statistical perspective. We begin by summarizing several of the key points under discussion, followed by our own commentary on these issues from a statistical point of view. We conclude our discussion by contemplating whether it may be time to move beyond the correlation and multiple comparisons framework that is causing so much confusion and instead represent all relevant research questions as parameters in one coherent multilevel model. PMID- 26158970 TI - Reply to Comments on "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition". PMID- 26158971 TI - Study Habits, Skills, and Attitudes: The Third Pillar Supporting Collegiate Academic Performance. AB - Study habit, skill, and attitude inventories and constructs were found to rival standardized tests and previous grades as predictors of academic performance, yielding substantial incremental validity in predicting academic performance. This meta-analysis (N = 72,431, k = 344) examines the construct validity and predictive validity of 10 study skill constructs for college students. We found that study skill inventories and constructs are largely independent of both high school grades and scores on standardized admissions tests but moderately related to various personality constructs; these results are inconsistent with previous theories. Study motivation and study skills exhibit the strongest relationships with both grade point average and grades in individual classes. Academic specific anxiety was found to be an important negative predictor of performance. In addition, significant variation in the validity of specific inventories is shown. Scores on traditional study habit and attitude inventories are the most predictive of performance, whereas scores on inventories based on the popular depth-of-processing perspective are shown to be least predictive of the examined criteria. Overall, study habit and skill measures improve prediction of academic performance more than any other noncognitive individual difference variable examined to date and should be regarded as the third pillar of academic success. PMID- 26158972 TI - Why Precedent in Law (and Elsewhere) is Not Totally (or Even Substantially) About Analogy. AB - Cognitive scientists who conduct research on analogical reasoning often claim that precedent in law is an application of reasoning by analogy. In fact, however, law's principle of precedent, as well as the use of precedent in ordinary argument, is quite different. The typical use of analogy in law, including analogies to earlier decisions, involves retrieval of a source analog (or exemplar) from multiple candidates in order to help make the best decision now. But the legal principle of precedent requires that a prior decision be treated as binding even if the current decision maker disagrees with that decision. When the identity between a prior decision and the current question is obvious and inescapable, precedent thus imposes a constraint different from the effect of a typical argument by analogy. The importance of distinguishing analogy from precedent is not so much in showing that a common claim in the psychological literature is mistaken, but that making decisions under the constraints of binding precedent is an important form of decision deserving to be researched in its own right and that it has been ignored because of the erroneous conflation of constraint by precedent with reasoning by analogy. PMID- 26158973 TI - Thought Speed, Mood, and the Experience of Mental Motion. AB - This article presents a theoretical account relating thought speed to mood and psychological experience. Thought sequences that occur at a fast speed generally induce more positive affect than do those that occur slowly. Thought speed constitutes one aspect of mental motion. Another aspect involves thought variability, or the degree to which thoughts in a sequence either vary widely from or revolve closely around a theme. Thought sequences possessing more motion (occurring fast and varying widely) generally produce more positive affect than do sequences possessing little motion (occurring slowly and repetitively). When speed and variability oppose each other, such that one is low and the other is high, predictable psychological states also emerge. For example, whereas slow, repetitive thinking can prompt dejection, fast, repetitive thinking can prompt anxiety. This distinction is related to the fact that fast thinking involves greater actual and felt energy than slow thinking does. Effects of mental motion occur independent of the specific content of thought. Their consequences for mood and energy hold psychotherapeutic relevance. PMID- 26158974 TI - Styles of Learning and Thinking Matter in Instruction and Assessment. AB - There are two styles of learning and thinking: ability based and personality based. The former are assessed by maximum-performance tests, and the latter are assessed by typical-performance tests. We argue that both kinds of styles matter for instruction and assessment in school. In particular, shaping lessons based on an awareness that people learn and think in different ways can lead to improved instructional outcomes. We describe one ability-based theory and one personality based theory and present supporting data from multiple studies relevant to each. PMID- 26158975 TI - Incorporating Individual Differences Into the Science of Learning: Commentary on Sternberg et al. (2008). AB - Sternberg, Grigorenko, and Zhang (2008, this issue) make a valiant effort to reinvigorate the somewhat dormant field of cognitive style by showing the implications of cognitive style for instruction and assessment. In support of their call to differentiate instruction for different kinds of learners, they summarize evidence showing that people learn better from a broad instructional method that is sensitive to multiple cognitive styles than they do from a narrow instructional method that is mainly addressed to one cognitive style. In support of their call for using multiple measures of learning potential, they summarize evidence showing that learning outcomes are better predicted by multiple measures of learning potential than by a single measure. In this commentary, I briefly examine Sternberg et al.'s claim that cognitive styles matter for instruction and assessment. PMID- 26158976 TI - Applying the Theory of Successful Intelligence to Education-The Good, the Bad, and the Ogre: Commentary on Sternberg et al. (2008). AB - Sternberg, Grigorenko, and Zhang (2008) have presented a creative model for the application of research on intelligence and personality to education. There are many positive aspects of their effort. These include the coordination of individual differences in cognition and personality and their extension of the concept of intelligence beyond skills that can be tested in the normal testing paradigm. Although various parts of their approach have appeared elsewhere, the development of a single package containing all these ideas is a worthwhile improvement in thinking about education. They cite numerous studies in support of their efforts. However, a close examination of some of the major studies shows that this evidence, though not inconsistent with their claims, is not as strong as their review indicates. If one applies conventional psychometric criteria, simpler explanations than those they propose could be found. Their model of thinking styles is probably too complex for many practical applications. However, a good case can be made that the appropriate criterion is "How useful will this approach be in education?" By this criterion, the total package is impressive and should be seriously considered by educators. PMID- 26158977 TI - A Reply to Two Stylish Critiques: Response to Hunt (2008) and Mayer (2008). AB - We reply to helpful critiques by Mayer (2008, this issue) and Hunt (2008, this issue) of our article on the role of styles of learning and thinking in instruction and assessment. We deal with issues of aptitude-treatment interaction, the range of variables important in instruction and assessment, the originality of our theories, overlap of our constructs with constructs in other theories, ethnic-group differences, and new data reported. PMID- 26158979 TI - Volume 3, 2008. PMID- 26158978 TI - Sex Differences in Variability in General Intelligence: A New Look at the Old Question. AB - The idea that general intelligence may be more variable in males than in females has a long history. In recent years it has been presented as a reason that there is little, if any, mean sex difference in general intelligence, yet males tend to be overrepresented at both the top and bottom ends of its overall, presumably normal, distribution. Clear analysis of the actual distribution of general intelligence based on large and appropriately population-representative samples is rare, however. Using two population-wide surveys of general intelligence in 11 year-olds in Scotland, we showed that there were substantial departures from normality in the distribution, with less variability in the higher range than in the lower. Despite mean IQ-scale scores of 100, modal scores were about 105. Even above modal level, males showed more variability than females. This is consistent with a model of the population distribution of general intelligence as a mixture of two essentially normal distributions, one reflecting normal variation in general intelligence and one refecting normal variation in effects of genetic and environmental conditions involving mental retardation. Though present at the high end of the distribution, sex differences in variability did not appear to account for sex differences in high-level achievement. PMID- 26158980 TI - Editor's Introduction: Special Issue on the Next Big Questions in Psychology. AB - In this issue of Perspectives on Psychological Science, we learn what 18 leading psychologists believe are the next big research questions in their respective fields. I invited about 20 of our most outstanding scholars to tell us what they believe are the most important questions to be asked in the upcoming decade. Not unexpectedly, the contributions are wide ranging both in content and in the way the authors framed the question of what is important. The range of articles, from psychoneuroimmunology to human-android interactions, clearly indicates the enormous scope of psychology. My hope is that both freshly minted and senior scientists alike might gain from these insights into the research they should pursue in the years ahead. PMID- 26158981 TI - Naive and Obvious Questions. AB - Psychology is the luckiest of the sciences because it owns the most interesting questions, the foremost being, "Why do people do what they do?" Naively, one might expect that research addressing this question would focus on the most important behaviors, but instead most studies choose behavioral dependent variables on the basis of their procedural feasibility and suitability for theory testing. The cumulative result is an uneven and unrepresentative map of the behavioral terrain. Situational variables are chosen in a similar manner with a parallel result. (Personality variables, in contrast, typically are designed to capture intrinsically important individual differences.) In this article, I proposes a simple research agenda that measures situational and behavioral variables selected on the basis of their intrinsic interest and consequentiality. This agenda promotes descriptive empirical research that is more likely to address the obvious (and good) questions that are the foundation of the widespread interest in psychology and to aid the development of theories that are interesting and widely relevant. PMID- 26158982 TI - The Nature (and Nurture?) of Plasticity in Early Human Development. AB - The effect of early experience is a long-standing concern in developmental psychology. Gaining further insight into the nature of human plasticity is central to efforts to prevent problems in development from arising and promote positive functioning. Evolutionary reasoning suggests that children should vary in their susceptibility to environmental influences, including parenting. Evidence indicates that rather than some children, such as those with negatively emotional temperaments or certain genotypes, being simply more vulnerable to the adverse effects of negative experiences, as commonly assumed, they may actually be more susceptible to both positive and negative experiences. In addition to raising questions about the nature of plasticity in human development, this article highlights unknowns regarding the role of nature and nurture in shaping individual differences in plasticity, including whether recent research linking maternal stress during pregnancy with child behavior problems illuminates a process whereby fetal programming shapes the child's susceptibility to postnatal environmental influences. Throughout this article, we raise concern about the potentially distorting influence that psychology's disproportionate focus on the adverse effect of negative experiences on developmental problems has on our understanding of human plasticity, and we propose that researchers should pay more attention to the positive side of the plasticity equation. PMID- 26158983 TI - How Can Evolutionary Psychology Successfully Explain Personality and Individual Differences? AB - Although evolutionary psychology has been successful in explaining some species typical and sex-differentiated adaptations, a large question that has largely eluded the field is this: How can the field successfully explain personality and individual differences? This article highlights some promising theoretical directions for tackling this question. These include life-history theory, costly signaling theory, environmental variability in fitness optima, frequency dependent selection, mutation load, and flexibly contingent shifts in strategy according to environmental conditions. Tackling the explanatory question also requires progress on three fronts: (a) reframing some personality traits as forms of strategic individual differences; (b) providing a nonarbitrary, evolutionary based formulation of environments as distributions and salience profiles of adaptive problems; and (c) identifying which strategies thrive and which falter in these differing problem-defined environments. PMID- 26158984 TI - How to Tell If a Particular Memory Is True or False. AB - How can you tell if a particular memory belonging to you or someone else is true or false? Cognitive scientists use a variety of techniques to measure groups of memories, whereas police, lawyers, and other researchers use procedures to determine whether an individual can be believed or not. We discuss evidence from behavioral and neuroimaging studies and research on lying that have attempted to distinguish true from false memories. PMID- 26158985 TI - How Can Decision Making Be Improved? AB - The optimal moment to address the question of how to improve human decision making has arrived. Thanks to 50 years of research by judgment and decision making scholars, psychologists have developed a detailed picture of the ways in which human judgment is bounded. This article argues that the time has come to focus attention on the search for strategies that will improve bounded judgment because decision-making errors are costly and are growing more costly, decision makers are receptive, and academic insights are sure to follow from research on improvement. In addition to calling for research on improvement strategies, this article organizes the existing literature pertaining to improvement strategies and highlights promising directions for future research. PMID- 26158986 TI - Know Thyself. AB - Self-knowledge has never been a central topic; in empirical psychology. There are pockets of research on self-knowledge in different subdisciplines of the field, but until now there has been little communication between them. I believe that these areas will converge in the next few years into a cohesive study of how people form judgments about their past, current, and future selves and about the accuracy of these judgments. I discuss theoretical developments in this area, the costs of poor self-knowledge, how people can know themselves better, and some of the obstacles to the study of self-knowledge. PMID- 26158987 TI - Giving Debiasing Away: Can Psychological Research on Correcting Cognitive Errors Promote Human Welfare? AB - Despite Miller's (1969) now-famous clarion call to "give psychology away" to the general public, scientific psychology has done relatively little to combat festering problems of ideological extremism and both inter- and intragroup conflict. After proposing that ideological extremism is a significant contributor to world conflict and that confirmation bias and several related biases are significant contributors to ideological extremism, we raise a crucial scientific question: Can debiasing the general public against such biases promote human welfare by tempering ideological extremism? We review the knowns and unknowns of debiasing techniques against confirmation bias, examine potential barriers to their real-world efficacy, and delineate future directions for research on debiasing. We argue that research on combating extreme confirmation bias should be among psychological science's most pressing priorities. PMID- 26158988 TI - Perspectives on Preference Aggregation. AB - For centuries, the mathematical aggregation of preferences by groups, organizations, or society itself has received keen interdisciplinary attention. Extensive theoretical work in economics and political science throughout the second half of the 20th century has highlighted the idea that competing notions of rational social choice intrinsically contradict each other. This has led some researchers to consider coherent democratic decision making to be a mathematical impossibility. Recent empirical work in psychology qualifies that view. This nontechnical review sketches a quantitative research paradigm for the behavioral investigation of mathematical social choice rules on real ballots, experimental choices, or attitudinal survey data. The article poses a series of open questions. Some classical work sometimes makes assumptions about voter preferences that are descriptively invalid. Do such technical assumptions lead the theory astray? How can empirical work inform the formulation of meaningful theoretical primitives? Classical "impossibility results" leverage the fact that certain desirable mathematical properties logically cannot hold in all conceivable electorates. Do these properties nonetheless hold true in empirical distributions of preferences? Will future behavioral analyses continue to contradict the expectations of established theory? Under what conditions do competing consensus methods yield identical outcomes and why do they do so? PMID- 26158989 TI - Achieving and Sustaining a Good Life. AB - How can we live well? To answer this question, psychology must acknowledge and integrate its descriptive and prescriptive components. One of psychology's strengths has been its willingness to embrace different purposes, perspectives, and approaches, and this recommendation is in the spirit of the field's history. At present, psychology knows more about people's problems and how to solve them than it does about what it means to live well and how to encourage and maintain such a life. Moreover, what is known is often fragmented because of psychology's specialization. Our article calls for further discussion in psychological terms of what it means to live well; the study of actual people and how they behave; multivariate, multimethod, and longitudinal research; more sophisticated interventions; interdisciplinary collaboration; and translational research. PMID- 26158990 TI - Human-Android Interaction in the Near and Distant Future. AB - In this article, a psychologist and an artificial-intelligence (AI) researcher speculate on the future of social interaction between humans and androids (robots designed to look and act exactly like people). We review the trajectory of currently developing robotics technologies and assess the level of android sophistication likely to be achieved in 50 years time. On the basis of psychological research, we consider obstacles to creating an android indistinguishable from humans. Finally, we discuss the implications of human android social interaction from the standpoint of current psychological and AI research and speculate on the novel psychological issues likely to arise from such interaction. The science of psychology will face a remarkable new set of challenges in grappling with human-android interaction. PMID- 26158991 TI - What Kind of Empirical Research Should We Publish, Fund, and Reward?: A Different Perspective. AB - When evaluating empirical papers for publication, grant proposals, or individual contributions (e.g., awarding tenure), the basic question one should ask is how much the contribution adds to understanding in psychology and not whether the contribution takes a particular form or represents one particular model of how to do empirical studies. Academic psychology has flourished with its mastery of the hypothesis-experiment model of science and its expertise in generating and eliminating alternative hypotheses and isolating causation. These accomplishments are a critical part of psychology, and they are well and appropriately taught by psychologists. However, they are only a part of science and should not comprise the almost exclusive criteria for evaluating research. In particular, discovery of fundamental phenomena, such as functional relations that apply to the real world and have generality, should have a higher priority in psychology. Such findings have been the basis for theoretical advances in other natural sciences. PMID- 26158992 TI - Beyond Money: Toward an Economy of Well-Being. AB - Policy decisions at the organizational, corporate, and governmental levels should be more heavily influenced by issues related to well-being-people's evaluations and feelings about their lives. Domestic policy currently focuses heavily on economic outcomes, although economic indicators omit, and even mislead about, much of what society values. We show that economic indicators have many shortcomings, and that measures of well-being point to important conclusions that are not apparent from economic indicators alone. For example, although economic output has risen steeply over the past decades, there has been no rise in life satisfaction during this period, and there has been a substantial increase in depression and distrust. We argue that economic indicators were extremely important in the early stages of economic development, when the fulfillment of basic needs was the main issue. As societies grow wealthy, however, differences in well-being are less frequently due to income, and are more frequently due to factors such as social relationships and enjoyment at work. Important noneconomic predictors of the average levels of well-being of societies include social capital, democratic governance, and human rights. In the workplace, noneconomic factors influence work satisfaction and profitability. It is therefore important that organizations, as well as nations, monitor the well-being of workers, and take steps to improve it. Assessing the well-being of individuals with mental disorders casts light on policy problems that do not emerge from economic indicators. Mental disorders cause widespread suffering, and their impact is growing, especially in relation to the influence of medical disorders, which is declining. Although many studies now show that the suffering due to mental disorders can be alleviated by treatment, a large proportion of persons with mental disorders go untreated. Thus, a policy imperative is to offer treatment to more people with mental disorders, and more assistance to their caregivers. Supportive, positive social relationships are necessary for well-being. There are data suggesting that well-being leads to good social relationships and does not merely follow from them. In addition, experimental evidence indicates that people suffer when they are ostracized from groups or have poor relationships in groups. The fact that strong social relationships are critical to well-being has many policy implications. For instance, corporations should carefully consider relocating employees because doing so can sever friendships and therefore be detrimental to well-being. Desirable outcomes, even economic ones, are often caused by well-being rather than the other way around. People high in well-being later earn higher incomes and perform better at work than people who report low well-being. Happy workers are better organizational citizens, meaning that they help other people at work in various ways. Furthermore, people high in well-being seem to have better social relationships than people low in well-being. For example, they are more likely to get married, stay married, and have rewarding marriages. Finally, well-being is related to health and longevity, although the pathways linking these variables are far from fully understood. Thus, well-being not only is valuable because it feels good, but also is valuable because it has beneficial consequences. This fact makes national and corporate monitoring of well-being imperative. In order to facilitate the use of well-being outcomes in shaping policy, we propose creating a national well-being index that systematically assesses key well-being variables for representative samples of the population. Variables measured should include positive and negative emotions, engagement, purpose and meaning, optimism and trust, and the broad construct of life satisfaction. A major problem with using current findings on well-being to guide policy is that they derive from diverse and incommensurable measures of different concepts, in a haphazard mix of respondents. Thus, current findings provide an interesting sample of policy-related findings, but are not strong enough to serve as the basis of policy. Periodic, systematic assessment of well being will offer policymakers a much stronger set of findings to use in making policy decisions. PMID- 26158993 TI - The Psychology of Confessions: A Review of the Literature and Issues. AB - Recently, in a number of high-profile cases, defendants who were prosecuted, convicted, and sentenced on the basis of false confessions have been exonerated through DNA evidence. As a historical matter, confession has played a prominent role in religion, in psychotherapy, and in criminal law-where it is a prosecutor's most potent weapon. In recent years, psychologists from the clinical, personality, developmental, cognitive, and social areas have brought their theories and research methods to bear on an analysis of confession evidence, how it is obtained, and what impact it has on judges, juries, and other people. Drawing on individual case studies, archival reports, correlational studies, and laboratory and field experiments, this monograph scrutinizes a sequence of events during which confessions may be obtained from criminal suspects and used as evidence. First, we examine the preinterrogation interview, a process by which police target potential suspects for interrogation by making demeanor-based judgments of whether they are being truthful. Consistent with the literature showing that people are poor lie detectors, research suggests that trained and experienced police investigators are prone to see deception at this stage and to make false-positive errors, disbelieving people who are innocent, with a great deal of confidence. Second, we examine the Miranda warning and waiver, a process by which police apprise suspects of their constitutional rights to silence and to counsel. This important procedural safeguard is in place to protect the accused, but researchers have identified reasons why it may have little impact. One reason is that some suspects do not have the capacity to understand and apply these rights. Another is that police have developed methods of obtaining waivers. Indeed, innocent people in particular tend to waive their rights, naively believing that they have nothing to fear or hide and that their innocence will set them free. Third, we examine the modern police interrogation, a guilt-presumptive process of social influence during which trained police use strong, psychologically oriented techniques involving isolation, confrontation, and minimization of blame to elicit confessions. Fourth, we examine the confession itself, discussing theoretical perspectives and research on why people confess during interrogation. In particular, we focus on the problem of false confessions and their corrupting influence in cases of wrongful convictions. We distinguish among voluntary, compliant, and internalized false confessions. We describe personal risk factors for susceptibility to false confessions, such as dispositional tendencies toward compliance and suggestibility, youth, mental retardation, and psychopathology. We then examine situational factors related to the processes of interrogation and show that three common interrogation tactics isolation; the presentation of false incriminating evidence; and minimization, which implies leniency will follow-can substantially increase the risk that ordinary people will confess to crimes they did not commit, sometimes internalizing the belief in their own culpability. Fifth, we examine the consequences of confession evidence as evaluated by police and prosecutors, followed by judges and juries in court. Research shows that confession evidence is inherently prejudicial, that juries are influenced by confessions despite evidence of coercion and despite a lack of corroboration, and that the assumption that "I'd know a false confession if I saw one" is an unsubstantiated myth. Finally, we address the role of psychologists as expert witnesses and suggest a number of possible safeguards. In particular, we argue that there is a need to reform interrogation practices that increase the risk of false confessions and recommend a policy of mandatory videotaping of all interviews and interrogations. PMID- 26158994 TI - The Devil in Confessions. PMID- 26158995 TI - Flawed Self-Assessment: Implications for Health, Education, and the Workplace. AB - Research from numerous corners of psychological inquiry suggests that self assessments of skill and character are often flawed in substantive and systematic ways. We review empirical findings on the imperfect nature of self-assessment and discuss implications for three real-world domains: health, education, and the workplace. In general, people's self-views hold only a tenuous to modest relationship with their actual behavior and performance. The correlation between self-ratings of skill and actual performance in many domains is moderate to meager-indeed, at times, other people's predictions of a person's outcomes prove more accurate than that person's self-predictions. In addition, people overrate themselves. On average, people say that they are "above average" in skill (a conclusion that defies statistical possibility), overestimate the likelihood that they will engage in desirable behaviors and achieve favorable outcomes, furnish overly optimistic estimates of when they will complete future projects, and reach judgments with too much confidence. Several psychological processes conspire to produce flawed self-assessments. Research focusing on health echoes these findings. People are unrealistically optimistic about their own health risks compared with those of other people. They also overestimate how distinctive their opinions and preferences (e.g., discomfort with alcohol) are among their peers-a misperception that can have a deleterious impact on their health. Unable to anticipate how they would respond to emotion-laden situations, they mispredict the preferences of patients when asked to step in and make treatment decisions for them. Guided by mistaken but seemingly plausible theories of health and disease, people misdiagnose themselves-a phenomenon that can have severe consequences for their health and longevity. Similarly, research in education finds that students' assessments of their performance tend to agree only moderately with those of their teachers and mentors. Students seem largely unable to assess how well or poorly they have comprehended material they have just read. They also tend to be overconfident in newly learned skills, at times because the common educational practice of massed training appears to promote rapid acquisition of skill-as well as self-confidence-but not necessarily the retention of skill. Several interventions, however, can be introduced to prompt students to evaluate their skill and learning more accurately. In the workplace, flawed self assessments arise all the way up the corporate ladder. Employees tend to overestimate their skill, making it difficult to give meaningful feedback. CEOs also display overconfidence in their judgments, particularly when stepping into new markets or novel projects-for example, proposing acquisitions that hurt, rather then help, the price of their company's stock. We discuss several interventions aimed at circumventing the consequences of such flawed assessments; these include training people to routinely make cognitive repairs correcting for biased self-assessments and requiring people to justify their decisions in front of their peers. The act of self-assessment is an intrinsically difficult task, and we enumerate several obstacles that prevent people from reaching truthful self-impressions. We also propose that researchers and practitioners should recognize self-assessment as a coherent and unified area of study spanning many subdisciplines of psychology and beyond. Finally, we suggest that policymakers and other people who makes real-world assessments should be wary of self assessments of skill, expertise, and knowledge, and should consider ways of repairing self-assessments that may be flawed. PMID- 26158996 TI - Blissfully Incompetent. PMID- 26158997 TI - In Response. PMID- 26158998 TI - Case closed: An economical treatment protocol for peristomal skin excoriation. PMID- 26158999 TI - Author's reply. PMID- 26159000 TI - Benefits of Meeting the Contraceptive Needs of Malawian Women. AB - (1) In 2013, an estimated 54% of pregnancies in Malawi were unintended. (2) More than four in 10 women have an unmet need for modern contraception-that is, they want to avoid pregnancy, but either are not practicing contraception or are using a relatively ineffective traditional method. (3) Meeting just half of this unmet need would prevent 213,000 unintended pregnancies annually, which would result in 34,000 fewer unsafe abortions and 800 fewer maternal deaths each year. (4) If all unmet need for modern contraception were met, maternal mortality would decline by more than two-fifths, and unintended births and unsafe abortions would drop by 87%. (5) Investing in contraceptive commodities and services to fulfill all unmet need for modern contraception would result in a net annual savings of US$11 million (4.1 billion Malawi kwachas) over what would otherwise be spent on medical costs associated with unintended pregnancies and their consequences. (6) Expanding contraceptive services confers substantial benefits to women, their families and society. All stakeholders-including the Malawi government and the private sector-should increase their investment in modern contraceptive services. PMID- 26159001 TI - Sexual and Reproductive Health Needs of Adolescents in Zimbabwe. AB - (1) As of 2011, 38% of young Zimbabwean women have had sex by age 18, as have 23% of young men; this difference has widened over time. Females now first have sex nearly two years sooner than males. (2) One-quarter of 15-19-year-old women have started childbearing; one-third of all births to adolescents are unplanned (wanted later or not at all). (3) Favorable trends of rising modern contraceptive use in urban areas were likely interrupted by the worst of the economic crisis in 2008. Use among married adolescents declined in urban areas (from 50% in 2006 to 29% in 2011), even as it rose in rural areas (from 30% to 37%). (4) Patterns in unmet need for contraception followed suit: In urban areas, the proportion of married adolescents who wanted to postpone childbearing but were not using a method rose between 2006 and 2011(from 14% to 28%); among their counterparts in rural areas, unmet need fell from 20% to 15% over this period. (5) Single, sexually active adolescents have by far the greatest unmet need--62% as of 2011, compared with 19% among their married counterparts. (6) Existing policies need clarification to assure that no adolescent is illegally denied services because of age. Youth-friendly sexual and reproductive health programs should be prioritized so today's HIV-positive adolescents, many of whom have been infected since birth, do not transmit the virus to yet another generation. PMID- 26159002 TI - Test early, treat early; in search of a common approach to HIV treatment. PMID- 26159003 TI - Up to 70% of HIV-positive individuals report experiencing symptoms related to atopy. PMID- 26159004 TI - Anti-Aging Treatment Claims: the Promises vs. the Science. PMID- 26159005 TI - The rise of superbugs. Dangerous infections that are resistant to antibiotics are spreading and growing stronger, with dire consequences. Medical experts say it's a mess of our own making--and the clock is ticking on when and how we must solve it. The first in a three-part series. PMID- 26159006 TI - Perspective. Commander's introduction. PMID- 26159007 TI - Performance differences between male and female marines on standardized physical fitness tests and combat proxy tasks: identifying the gap. AB - OBJECTIVES: For decades women have been restricted from direct assignment to certain military occupational specialties such as infantry. These restrictions can limit the advancement of women through the ranks of military leadership. Thus, the purpose of this effort was to identify those physical requirements most likely to serve as barriers for women wanting to enter closed combat arms positions, and to evaluate the quality of existing physical fitness tests as potential measures of assessment of combat readiness. METHODS: Data were collected from 3 different sites within the US Marine Corps Training and Education Command. All participants (409 male, 379 femaile) were active-duty Marines who recently completed the Physical Fitness Test (PFT) and Combat Fitness Test (CFT). Participants completed 6 physical tasks: 120-mm tank loading drill, 155-mm artillery round carry, negotiating an obstacle course wall while wearing a fighting load (~30 lb), pull-ups, deadlift, and clean and press. RESULTS: Overall, there was a high rate of successful completion on the combat proxy tasks (men, ~80% to 100%; women, ~70% to 100%), with the notable exception being the clean and press (men, 80%; women, 9%) and pull-ups (men, 16+/-4; women, 4+/-2). The PFT and CFT components tasks were also related, strongly in some cases, with performance on combat-related proxy tasks (Spearman's rho typically ranged from 0.60 to 0.80). Estimates of fat-free mass and VO2max were also strongly related to an overall measure of combat readiness (Spearman's rho=0.77 and rho=0.56, respectively). CONCLUSIONS: The primary physical obstacle for women is upper body strength. However, some women could successfully complete all of the proxy tasks and thus are physically capable of meeting the demands of closed combat occupations. The fact that some female Marines could complete the most challenging upper body strength tasks suggests that these barriers are not inherent but may be due to a lack of training specificity. PMID- 26159008 TI - Does Medicaid Make a Difference? Findings from the Commonwealth Fund Biennial Health Insurance Survey, 2014. AB - As millions of Americans gain Medicaid coverage under the Affordable Care Act, attention has focused on the access to care, quality of care, and financial protection that coverage provides. This analysis uses the Commonwealth Fund Biennial Health Insurance Survey, 2014, to explore these questions by comparing the experiences of working-age adults with private insurance who were insured all year, Medicaid beneficiaries with a full year of coverage, and those who were uninsured for some time during the year. The survey findings suggest that Medicaid coverage provides access to care that in most aspects is comparable to private insurance. Adults with Medicaid coverage reported better care experiences on most measures than those who had been uninsured during the year. Medicaid beneficiaries also seem better protected from the cost of illness than do uninsured adults, as well as those with private coverage. PMID- 26159009 TI - How Insurers Competed in the Affordable Care Act's First Year. AB - Prior to the Affordable Care Act (ACA), most states' individual health insurance markets were dominated by one or two insurance carriers that had little incentive to compete by providing efficient services. Instead, they competed mainly by screening and selecting people based on their risk of incurring high medical costs. One of the ACA's goals is to encourage carriers to participate in the health insurance marketplaces and to shift the focus from competing based on risk selection to processes that increase consumer value, like improving efficiency of services and quality of care. Focusing on six states--Arkansas, California, Connecticut, Maryland, Montana, and Texas--this brief looks at how carriers are competing in the new marketplaces, namely through cost-sharing and composition of provider networks. PMID- 26159010 TI - [On the Conditionality of "Disease" in Treating Different Diseases with the Same Method]. AB - Treating different diseases with the same method is a unique original thinking in Chinese medicine, which embodies the spirit of treatment based on syndrome differentiation. We briefly reviewed the origin and development of this concept. We also reviewed that thinking of combination of disease and syndrome is its premise and foundation. We put forward the conditionality of diseases in treating different diseases with the same method by cutting-in modern biological basic researches, that is to say, one kind specific diseases or disease of one specific system. We emphasized the importance of diseases conditionality in treating different diseases with the same method, which was of great significance in studies on combination of disease and syndrome, correspondence of prescription and syndrome, and modern biological basic researches of treating different diseases with the same method. PMID- 26159011 TI - [Modern Recognition and Practice of Chronic Airway Inflammation Based Fei-Shen Qi Deficiency Syndrome Connotation]. PMID- 26159012 TI - [Treatment of Mild-to-moderate Bronchial Asthma (Heat Wheezing Syndrome) Patients at Acute Onset with Western Medicine Combined Danlong Oral Liquid: a Multi center, Randomized Double- blinded, Positive-controlled Clinical Trial]. AB - OBJECTIVE: To observe the efficacy and safety of Danlong Oral Liquid (DOL) combined Western medicine (WM) in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset. METHODS: Totally 480 mild-to moderate bronchial asthma patients (heat wheezing syndrome) at acute onset were randomly assigned to two groups in the ratio 3:1, the treatment group (360 cases) and the control group (120 cases). All patients received basic WM treatment. Patients in the treatment group took DOL, 10 mL each time, 3 times per day for 7 days in total, while those in the control group took Kechuanning Oral Liquid (KOL) , 10 mL each time, 3 times per day for 7 days in total. Efficacy for asthma symptoms, lung functions and scores of TCM syndrome and/or main symptoms were evaluated. RESULTS: The percentage of clinical control and significant effectiveness of asthma symptoms in the treatment group was significantly higher than that of the control group (77.36% vs 56.07%, P < 0.01). The percentage of clinical control and significant effectiveness of lung functions in the treatment group was significantly higher than that of the control group (74.28% vs 50.00%, P < 0.01). The anterior-posterior difference in scores of TCM syndrome was significantly superior in the treatment group than in the control group (-11.26 +/- 4.70 vs -9.21 +/- 5.09, P < 0.01). The anterior-posterior difference in scores of main symptoms was significantly better in the treatment group than in the control group (-6.58 +/- 3.08 vs -5.16 +/- 3.45, P < 0.01). The incidence of adverse reactions was significantly lower in the treatment group than in the control group [1.73% (6/346 cases) vs 10.17% (12/118 cases) , P < 0.05]. CONCLUSION: DOL combined WM was superior to KOL in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset. PMID- 26159013 TI - [Effect of Peitu Shengjin Recipe on Nutritional States and Immune Functions of Stable Phase COPD Patients]. AB - OBJECTIVE: To explore the effect of Peitu Shengjin Recipe (PSR) on nutritional states and immune functions of stable phase chronic obstructive pulmonary disease (COPD) patients. METHODS: Totally 62 stable phase COPD patients were randomly assigned to the treatment group (30 cases) and the control group (32 cases). All patients inhaled Seretide (50/500 ug), twice per day. Besides, patients in the treatment group additionally received PSR, one dose per day. After three months of treatment, the COPD assessment test (CAT) score, the index of nutritional states [including body mass index (BMI) , thickness of skin fold (TSF), mid-arm muscle circumference (MAMC), serum albumin, serum prealbumin], and immune functions (including IgA, IgM, and IgG) were compared between the two groups. RESULTS: By the end of the treatment, the CAT score decreased more obviously in the treatment group than in the control group (P < 0.05). The improvement of BMI, TSF, MAMC, serum albumin, and serum prealbumin was better in the treatment group than in the control group (P < 0.05). IgM and IgG also increased more in the treatment group (P < 0.05). There was no statistical difference in IgA between the two groups (P > 0.05). CONCLUSIONS: Additionally use of PSR could improve nutritional states and immune functions of stable phase COPD patients to some extent. Meanwhile, it also could improve their health related quality of life. PMID- 26159014 TI - [Effect of Qi Benefiting Blood Activating Method on Plasma Fibrinogen and D-dimer in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease]. AB - OBJECTIVE: To explore the therapeutic effect of qi benefiting blood activating method (QB-BAM) on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with blood stasis syndrome (BSS) by observing its effect on plasma fibrinogen (Fg) and D-dimer (D-D) levels. METHODS: Sixty AECOPD patients with BSS were randomly assigned to the treated group and the control group, 30 in each group. All patients received conventional therapy for AECOPD. Those in the treated group were additionally injected with Shengmai Injection and Tanshinone IIA Injection. Clinical efficacy and indices including levels of Fg, D-D, PaO2, and PaCO2 were measured and compared before and after treatment. RESULTS: The effective rate was 93.3% (28/30 cases) in the treated group, higher than that of the control group [73.3% (22/30 cases) , P < 0.05]. There was no significant difference in all indices between the treated group and the control group before treatment (P >0.05). After treatment all indices were significantly improved in the two groups (P < 0.01). But in the treated group levels of Fg and D-D decreased more and levels of PaO2 increased more (P < 0.01). Plasma levels of Fg and D-D levels were negatively correlated with PaO2 (r = -0.493, r = -0.438, P < 0.01) before treatment, and also negatively correlated with PaO2 (r = -0.452, r = -0.325, P < 0.01, P < 0.05) after treatment, but they were not significantly correlated with PaCO2 before and after treatment (P >0.05). CONCLUSIONS: QBBAM could play a therapeutic role in improving prethrombotic states of AECOPD patients with BSS. Plasma levels of Fg and D-D were related to the severity of AECOPD. PMID- 26159015 TI - [Effect of Qingfei Decoction on Nitric Oxide and 8-isoPG in Exhaled Breath Condensate of ARDS Patients]. AB - OBJECTIVE: To observe the clinical significance of nitric oxide (NO) and 8 isoprostane (8-isoPG) changes in exhaled breath condensate ( EBC) of acute respiratory distress syndrome (ARDS) patients after treated by Qingfei Decoction (QD). METHODS: Totally 48 ARDS patients receiving mechanical ventilation were equally assigned to the QD treatment group and the control group by random digit table. EBC specimens were collected by modified Ecoscreen breath condensate collector (German JAEGER Company) on the first day and the fifth day after confirmed diagnosis of ARDS. Concentrations of NO and 8-isoPG in EBC were measured by ELISA. The oxygenation index and APACHE II scores were recorded at the same time. RESULTS: (1) The fatality rate in the QD treatment group was lower than that in the control group (8.3% vs 37.5%, P < 0.05). (2) After treatment NO and 8-isoPG concentrations in EBC were lower in the QD treatment group (34.49 +/- 5.67 umol/L, 30.09 +/- 7.89 ng/L) than in the control group (39.78 +/- 9.27 umol/L, 35.65 +/- 8.90 ng/L; P < 0.05). (3) After treatment improved oxygenation index value was higher in the QD treatment group than in the control group (120.88 +/- 35.16 vs 101.50 +/- 37.70, P < 0.05). After treatment APACHEII scores was lower in the QD treatment group than in the control group (6.21 +/- 3.51 vs 10. 26 +/- 4.33, P < 0.05). CONCLUSION: Treatment of ARDS patients by QD was favorable in controlling inflammation, alleviating lung injury, and improving clinical efficacy. PMID- 26159016 TI - [Treatment of Intractable Pediatric Mycoplasma Pneumonia by Qingfei Huoxue Recipe Combined Azithromycin: a Random Parallel Control Study]. AB - OBJECTIVE: To explore the effect of Qingfei Huoxue Recipe (QHR) combined azithromycin in treatment of intractable pediatric mycoplasma pneumonia. METHODS: Totally 124 intractable pediatric mycoplasma pneumonia patients at our hospital were recruited in this study, and randomly assigned to the treatment group and the control group, 62 in each group. Patients in the control group took azithromycin, while those in the treatment group additionally took QHR. All patients received omnibearing systematic nursing. Therapeutic efficacy, clinical indices (such as disappearance time of cough and rales, recovery time of body temperature) , and the incidence of adverse reactions were observed. RESULTS: After treatment the total effective rate was 91.94% (57/62 cases) in the treatment group and 77. 42% (48/62 cases) in the control group with statistical difference (P < 0.05). Compared with the control group, disappearance time of cough and rales, recovery time of body temperature were obviously shortened in the treatment group with statistical difference (P < 0.01). There was statistical difference in the incidence of adverse reactions between the two groups [3.23% (2/62 cases) vs 38.71% (24/62 cases) , P < 0.01]. CONCLUSION: In clinical treatment for intractable pediatric mycoplasma pneumonia, Chinese medicine combined Western medicine plus scientific and systematic nursing showed more obvious advantages with significant efficacy, which was worth spreading. PMID- 26159017 TI - [Effect of Acupuncture Combined Physical Training and Relearning on Stroke Rehabilitation: a Multi-center Randomized Controlled Clinical Study]. AB - OBJECTIVE: To observe the effect of acupuncture combined physical training and relearning on stroke patients. METHODS: A multi-center, randomized controlled trial design was adopted. A total of 364 stroke patients were recruited and randomly assigned to the experimental group (184 cases) and the control group (180 cases). Patients in the experimental group received acupuncture combined with physical training and relearning, while those in the control group only received physical training and relearning. All received four weeks of treatment. Effects on Fugl-Meyer motor function, neurological impairment, activities of daily living difference were compared before treatment, after treatment, 2 and 5 months after follow-ups between the two groups. RESULTS: Totally 353 patients completed this trial, 179 in the experimental group and 174 in the control group. (1) compared with before treatment, brief Fugl-Meyer motor functions scores and FIM scored obviously increased, and scores for neurological impairment obviously decreased in the two group. Besides, the increment of brief Fugl-Meyer motor functions scores and FIM scores was obviously higher in the experimental group than in the control group at month 2 and 5 of follow-ups; scores for neurological impairment was obviously lower in the experimental group than in the control group. The increment of FIM scores was obviously higher in the experimental group than in the control group at month 5 of follow-ups (P < 0.05, P < 0.01). (2) There was statistical difference in inter-group comparison of total Fugl-Meyer motor functions scores and FIM scores, or scores for neurological impairment (P < 0.01). The improvement of Fugl-Meyer motor functions grading and neurological impairment grading was obviously superior in the experimental group at month 2 and 5 of follow-ups. The distribution of FIM grading was also better in the experimental group at month 5 of follow-ups (P < 0.05, P < 0. 01). CONCLUSIONS: Both acupuncture combined exercise training and relearning and physical training and relearning could effectively promote the rehabilitation of stroke patients, reduce their neurological impairment degrees, improve motor functions and independent capacities. Better long-term efficacy could be obtained by acupuncture combined exercise training and relearning. PMID- 26159018 TI - [Design and Application of Distal Radius Anatomical Shape Bracket Splints]. AB - OBJECTIVE: To observe the clinical effect of anatomic shape bracket splints designed by 3D-MAX software. METHODS: Healthy adult volunteers' forearms and wrist data were measured and processed by 3D-MAX software. Then we designed and made anatomic shape bracket splints. Totally 60 distal radial fracture patients were equally assigned to the test group and the control group. After manual reduction, patients in the test group used anatomic shape bracket splints, while those in the control group used common splints. The palmar dip angle, ulnar fleet angle, and radius height of standard X-ray in normal and lateral positions were measured after treatment, at 1, 3, and 6 week after treatment, respectively. Meanwhile, the incidence of complications was recorded during the whole treatment process. RESULTS: Compared with the control group, the palmar dip angle and ulnar fleet angle were larger in the test group after one week of treatment (P < 0.05). The radius height of the treatment group was higher after one, three, and six weeks of treatment (P < 0.05). Compared with the control group, the incidence of complications was obviously less in the test group (P < 0.05). CONCLUSIONS: Anatomic shape bracket splints designed by 3D-MAX software fit local anatomic features and need no more shaping. Its easier use with lesser complications could maintain the stability of bone fracture better. PMID- 26159019 TI - [The Relationship Study between Expressions of P2X5 Receptor and Deficiency-cold Syndrome/Deficiency-heat Syndrome at Various Ambient Temperatures]. AB - OBJECTIVE: To detect the expression of the peripheral blood P2X5 receptor at various ambient temperatures, and to explore its relationship with deficiency cold syndrome and deficiency-heat syndrome. METHODS: Subjects were selected by questionnaire and expert diagnosis, and assigned to the normal control group, the deficiency-cold syndrome group, and the deficiency-heat syndrome group, 20 in each group. 5 mL venous blood was collected at room temperature (25 degrees C) and cold temperature (-4-5 degrees C) respectively. Then the expression of P2X5 receptor was relatively quantified by real-time fluorescence quantitative PCR, and compared at room temperature and cold temperature respectively. RESULTS: The expression of P2X5 receptor in deficiency-cold syndrome and deficiency-heat syndrome groups was lower than that in the normal control group at room temperature (P < 0.05). It decreased more at cold temperature in the deficiency cold syndrome group than in the normal control group (P < 0.01) as well as in the deficiency-heat syndrome group (P < 0.05). The expression of P2X5 receptor showed no difference in all groups at two different temperatures (P > 0.05). CONCLUSIONS: The expression of P2X5 receptor was different in different syndrome groups at various ambient temperatures. Ambient temperatures had insignificant effect on the expression of P2X5 receptor of the population with the same syndrome. PMID- 26159020 TI - [Efficacy of Chinese Herbs for Supplementing Qi and Activating Blood Circulation on Patients with Acute Coronary Syndrome and Type 2 Diabetes Mellitus after Percutaneous Coronary Intervention: a Clinical Observation]. AB - OBJECTIVE: To observe the efficacy of Chinese herbs for supplementing qi and activating blood circulation (CHSQABC) on patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM) after successful percutaneous coronary intervention (PCI). METHODS: In this ChiCTR-TRC-00000021, a total of 281 ACS patients complicated with type 2 DM after successful PCI were randomly assigned to the Western medicine treatment group (the control group, treated by routine Western medicine treatment) and the combined treatment group (the treatment group, treated by CHSQABC + routine Western medicine treatment). Patients in the combined treatment group took Xinyue Capsule (2 pills each time, 3 times per day) and Compound Chuanxiong Capsule (2 pills each time, 3 times per day for half a year and 1-year follow-ups). Primary endpoints covered incidence of death, nonfatal myocardial infarction (MI), ischemia-driven revascularization, and secondary endpoints included stroke, heart failure, and rehospitalization for ACS. At the same time scores for blood stasis syndrome (BSS) and the incidence of angina pectoris were evaluated before treatment, at month 1, 3, 6, 9, and 12 after treatment. RESULTS: The incidence of ischemia-driven revascularization was obviously less in the treatment group than in the control group (P < 0.05). No patient had nonfatal MI in the treatment group, while 5 patients in the control group had it. The incidence of non-fatal MI showed an obvious lowering tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). Four patients readmitted to hospital in the treatment group, while 12 patients readmitted. There existed obvious tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). The incidence of angina was significantly lower in the treatment group at month 6, 9, and 12 than that at month 1 , but it was lower in the control group at 9 months (P < 0.05). The incidence of angina was 15. 4% in the treatment group, obviously lower than that in the control group (26.2%, P < 0.05). Compared with before treatment, scores for BSS were obviously lowered in the treatment group at 1, 3, 6, 9, and 12 months of treatment and in the control group at 3, 6, 9, and 12 months of treatment (P < 0.05). It was obviously lower in the treatment group than in the control group at 3, 6, 9, and 12 months of treatment (P < 0.01). CONCLUSION: Administration of CHSQABC combined routine Western medicine treatment could reduce the event of revascularization and post-PCI recurrent angina, and improve scores for BSS of ACS patients complicated with DM after PCI. PMID- 26159021 TI - [The Incidence of Hypertension in Beijing Region Based on Yun-qi Theory: an Exploratory Research]. AB - OBJECTIVE: To explore the scientificity of Yunqi theory based on incidence of disease related recognitions such as year evolutive phase, host climatic qi, six climatic factors, celestial manager qi, qi in the earth by analyzing data of hypertension incidence. METHODS: A total of 1,265 inpatients with confirmed first diagnosis as hypertension were recruited at Dongzhimen Hospital, Beijing University of Chinese Medicine from February 4, 1999 to February 4, 2011. Each period (including year evolutive phase, host climatic qi, guest climatic qi) was deducted based on Yun-qi theory. Their ratios of different phases and qi in the total number of hypertension inpatients number were calculated and statistically tested. RESULTS: There was statistical difference in ratios at year evolutive phase, celestial manager qi, and qi in the earth (P < 0.05). CONCLUSION: The incidence of hypertension has certain difference in each period, which is consistent with Yun-qi theory. PMID- 26159022 TI - [Study on Inhibitory Effect of Aqueous Extract of Taxus Chinensis var. mairei Combined Erlotnib on A549 Xenograft in Nude Mice and Its Mechanism]. AB - OBJECTIVE: To study the effect of aqueous extract of Taxus chinensis var. mairei (AETC) combined Erlotnib on the growth of A549 xenograft in nude mice and its mechanism. METHODS: The xenograft model in nude mice was established by inoculating A549 cells subcutaneously. BALB/c nude mice bearing A549 xenograft were randomly divided into six groups, i.e., the low dose Erlotinib group (A) , the standard dose Erlotnib group (B) , the low dose Erlotinib combined AETC group (C), the standard dose Erlotnib combined AETC group (D), the AETC group (E), the control group (F), 12 in each group. Different medication was performed for 7 successive weeks after 24 h. One mL blood was withdrawn and tumor tissues taken. The tumor inhibition rate was calculated. The combined effect was analyzed by Jin's Formula [Q = Ea + b/(Ea + Eb-Ea x Eb) ]. mRNA and protein expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), and B cell lymphoma-2 (Bcl-2) in xenografts were detected using real-time RT-PCR and ELISA. RESULTS: Compared with Group F, the xenograft weight was obviously lowered in Group B-E (P < 0.05, P < 0.01). The q value was 0.92 in Group C and 0.96 in Group D, which was obtained by simple adding of the two drugs. Compared with Group F, EG- FR mRNA expression in Group D and E, COX-2 mRNA expression in Group A-E; Bcl 2 mRNA expression in Group B-D; COX-2 protein expression in Group B-E; Bcl-2 protein expression in Group C and D were obviously lowered with statistical difference (P < 0.05, P < 0.01). CONCLUSIONS: AETC combined low dose and standard dose Erlotinib had synergistic effect on tumor inhibition. Its mechanism might be associated with down-regulating mRNA and protein expression levels of COX-2 and Bcl-2. PMID- 26159023 TI - [Effect of 18-beta Glycyrrhetinic Acid on the Endoplasmic Reticulum of Nasal Epithelial Cells in Allergic Rhinitis Model Rats]. AB - OBJECTIVE: To explore the effect of 18-beta glycyrrhetinic acid (GA) on the endoplasmic reticulum of nasal epithelial cells in allergic rhinitis (AR) model rats. METHODS: Totally 96 Wistar rats were randomly divided into the blank group, the AR model group, the loratadine group, the GA group, 24 in each group. AR models were established by peritoneally injecting ovalbumin (OVA). Morphological scoring was performed. GA at 21. 6 mg/kg was intragastrically administered to rats in the GA group. Nasal mucosal tissues were taken for electron microscopic examinations at the second, fourth, sixth, and tenth week after drug intervention. RESULTS: The overlapping score was 2.10 +/- 0.45 in the blank group, 5.10 +/- 0.56 in the loratadine group, 5.10 +/- 0.56 in the AR model group, 5.20 +/- 0.78 in the GA group, showing statistical difference when compared with the blank group (P < 0.01). Results under transmission electron microscope showed that the number of the endoplasmic reticulum increased in the AR model group, with obvious cystic dilatation, a lot of vacuole formation, and degranulation. A large number of free ribosomes could be seen in cytoplasm. With persistent allergen exposure, changes mentioned above was progressively aggravated in the endoplasmic reticulum of nasal mucosal epithelium in the AR model group. But the dilation of endoplasmic reticulum, vacuole formation, and degranulation were relieved in the GA group, and got close to those of the blank group. CONCLUSION: 18-beta GA could improve the expansion, vacuolization, and degranulation of the endoplasmic reticulum of nasal epithelial cells in AR model rats. PMID- 26159024 TI - [Qangxin Granule Intervened Chronic Heart Failure Rats with Xin-qi Deficiency Complicated Blood Stasis and Edema Syndrome: an Experimental Study]. AB - OBJECTIVE: To study and evaluate the curative effect and mechanism of Qiangxin Granule (QXG) in intervening chronic heart failure (CHF) rats with Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BS-ES). METHODS: Totally 72 SD rats of clean grade were randomly divided to the normal control group (n =10) and the model group (n = 62). The XQD-BS-ES rat model was established by adriamycin plus propylthiouracil method. Survived modeled rats were then randomly divided to 5 groups i.e., the model group (n = 11, administered with normal saline by gastrogavage), the Western medicine (WM) group (n =11 , administered with perindopril and hydrochlorothiazide by gastrogavage), the low dose QXG (QXG(L)) group (n = 11, administered with 9.26 g/kg QXG by gastrogavage), the middle dose QXG (QXG(M)) group (n = 11, administered with 18.52 g/kg QXG by gastrogavage), the high dose QXG (QXG(H)) group (n = 11, administered with 37.04 g/kg QXG by gastrogavage). After 4 weeks of treatment, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), tri-iodothyronine (T3), tetra-iodothyronine (T4), thyroid stimulating hormone (TSH), as well as heart, lung, liver weight index and their pathological sections, and high sensitivity C-reactive protein (HS-CRP), angiotensin II (Ang II), carbohydrate antigen 125 (CA125) were detected and compared. RESULTS: Compared with the normal control group, LVEF, LVFS, BNP, HR, RR, urine output, ear temperature, EST, T3, T4, TSH, HS-CRP, Ang II, and CA125 changed significantly in the model group (P < 0.01). Compared with the model group after treatment, LVEF, LVFS, BNP, urine output, EST, T4, heart and liver weight index, HS-CRP, Ang II, CA125 were significantly improved in each QXG group (P < 0.05, P < 0.01). Moreover, TSH was improved in the QXGL and QXG(M) groups (P < 0.05); ear temperature and T3 in the QXG(M) were also improved (P < 0.05); the lung weight index decreased in the QXG(M) and QXG(H) groups (P < 0.01). Compared with the WM group, T4 and CA125 were obviously improved in all QXG groups (P < 0.01); BNP and ear temperature were obviously improved in QXG(L) and QXG(M) groups (P < 0.05, P < 0.01); LVEF, LVFS and TSH were obviously improved in the QXG(M) group (P < 0.05, P < 0.01). And as far as each treatment group, LVEF, LVFS, urine output increased significantly after treatment (P < 0.01); EST obviously increased in QXG(M) and QXG(H) groups (P < 0.01); ear temperature increased in all QXG groups (P < 0.05, P < 0.01). Moreover, compared with the model group, pathological changes of heart, lung, and liver were improved to some degree in each treatment group, especially in the QXG(M) group. CONCLUSIONS: Good curative effect was shown in each QXG group. QXG could improve LVEF, LVFS and BNP of CHF rats of XQD-BS-ES, as well as T3, T4, TSH, EST, urine output, and ear temperature. Moreover, QXG showed superiority than WM group in this respect. PMID- 26159025 TI - [Establishment of Uyghur Medicine Abnormal Savda Carrier MIRI Animal Model and its Cardiac Ultrastructural Changes]. AB - OBJECTIVE: To innovatively establish a new platform of myocardial ischemia reperfusion injury (MIRI) animal model by observing abnormal savda carrier MIRI indicators, and to observe changes of myocardial ultrastructure. METHODS: According to Uyghur medical theories, an abnormal savda carrier animal model was established and confirmed using multifactor, and then MIRI models set up. Totally 36 male white SD rats were randomly divided into the normal sham-operation group, the normal operation group, the model sham-operation group, and the model operation group, 9 in each group. ECG changes, myocardial enzymes (CK-MB), and cardiac troponin (cTnT), and ultramicrostructures were observed. RESULTS: Compared with the normal sham-operation group, some damage of ultramicrostructures occurred in heart muscles of rats in the normal operation group and the model operation group, such as lowered myoplasm density, loosely arranged myofilament, dilated myofibris, reduced mitochondria number, vacuole and swelling mitochondrion. Ultramicrostructural damage of cardiac muscle cells was more severe in rats of the model operation group. Compared with the normal sham operation group, CK-MB and cTnT increased in the normal operation group with statistical difference (P < 0.01). Compared with the normal sham-operation group, there was no statistical difference in CK-MB or cTnT in the model sham-operation group (P > 0.05). Compared with the model operation group, CK-MB and cTnT obviously decreased in the model sham-operation group and the normal operation group with statistical difference (all P < 0.01). CONCLUSION: Abnormal savda carrier MIRI model established in this experiment could provide favorable conditions for further MIRI intervention treatment. PMID- 26159026 TI - [Study on the Mechanism of Three Kinds Extracts of Qingxin Kaiqiao Recipe in Improving Learning and Memory Capabilities of AD Rats]. AB - OBJECTIVE: To explore the mechanism of three kinds extracts (saponins, volatile components, polysaccharide components) of Qingxin Kaiqiao Recipe (QKR) in improving learning and memory capabilities of Alzheimer's disease (AD) rats. METHODS: A controlled comparison method was used. Totally 56 male SD rats were randomly divided into seven groups, i.e., the normal control group, the sham operation group, the model group, the Aricept group, the saponin group, the benzene group, and the polysaccharide group, 8 in each group. AD rat model was established by bilateral hippocampus injection of Abeta1-40 (2 uL, 2.5 ug/uL). The next day after modeling rats in the saponin group, the benzene group, and the polysaccharide group, the saponin group, the Aricept group were intragastrically administered with saponin (at the daily dose of 9 mL/kg, 2.1 g/mL) , benzene (at the daily dose of 3.33 mL/kg, 5.7 g/mL) , polysaccharide (at the daily dose of 8.33 mL/kg, 2.28 g/mL), Aricept (at the daily dose of 1.67 mg/kg), respectively, once a day for 2 consecutive weeks from 10 am every day. Equal volume of normal saline was intragastrically administered to rats in the normal control group and the model group. Learning and memory capabilities were detected using water maze 2 weeks later. Expression levels of synaptotagmin-1 (Syt-1), interleukin-1beta (IL-1beta), glia fibrillary acidic protein (GFAP), and beta-amyloid precursor protein (betaAPP) in the cortex and hippocampus of AD rats were detected using immunohistochemistry. RESULTS: Learning and memory capabilities could be improved by three kinds extracts of QKR. There was no statistical difference in the escape latency between the polysaccharide group and the model group (P >0. 05). The escape lacency was shortened in the rest treatment groups (P < 0.05). The escape latency was obviously prolonged in three kinds extracts of QKR groups, when compared with the Aricept group (P < 0.05, P < 0.01). Compared with the model group, times for crossing platforms were significantly increased in the saponin group and the Aricept group (P < 0.05). Compared with the Aricept group, average times for crossing platforms were significantly lessened in three kinds extracts of QKR groups (P < 0.01). Compared with the sham-operation group, expression levels of Syt-1, IL-1beta, GFAP, and betaAPP in the cortex and hippocampus were increased in the model group (P < 0.01). Compared with the model group, the expression of cortical Syt-1 increased in the saponin group and the benzene group; the expression of cortical IL-1beta increased in the benzene group and the polysaccharide group; the expression of hippocampal GFAP increased in the three kinds extracts of QKR groups; expression levels of Syt-1, IL-1beta, GFAP, and beta-APP in the cortex and hippocampus decreased in the rest treatment groups (all P < 0.05, P < 0.01). Compared with the Aricept group, expression levels of Syt-1, IL-1beta, GFAP, and betaAPP in the cortex and hippocampus were significantly increased in three kinds extracts of QKR groups (P < 0.05, P < 0.01). CONCLUSION: Three kinds extracts of QKR might play roles in anti-AD possibly by decreasing expression levels of Syt-1, IL-1beta, GFAP, and betaAPP in the cortex and hippocampus. PMID- 26159027 TI - [The Analgesia of Oxymatrine Affecting Calcium Channel and GABA Release]. AB - OBJECTIVE: To explore the analgesia of oxymatrine (OMT) affecting high voltage dependent calcium channels (HVDCCs) and GABA release under neuropathic pain condition. METHODS: Totally 66 C57BL/6 mice were randomly divided into the sham operation group, the model group, and the OMT group, 22 in each group. Neuropathic pain models were established by partial sciatic nerve ligation (PSNL). Hind paw plantar mechanical response threshold (MWT) was measured by up and-down method with Von-Frey filament. mRNA expression of HVDCCs in brains and spinal cords was detected with Real-time PCR and concentration of GABA was determined using ELISA kit. RESULTS: Compared with day 0, the left hind paw MWTwas decreased on day 7, 10, and 14 in the model group (P < 0.05). Compared with the sham-operation group, the left hind paw MWT was significantly reduced in the model group on day 7 (P < 0.05). The MWT of PSNL ipsilateral hind paw was decreased on day 7 before OMT administration, when compared with day 0 (P < 0.05), and increased after OMT administration (P < 0.05). Compared with the sham operation group, mRNA levels of Cav1.2, Cav1.3, Cav2.1, and Cav2.3 in brain tissues were increased and those of Cav2.2 were decreased significantly in the model group (P < 0.05). In spinal cord tissues, mRNA levels of Cav1.2 and Cav1.3 were increased, but those of Cav2.1, Cav2.2, and Cav2. 3 were decreased significantly in the model group, when compared with those of the sham-operation group (P < 0.05). Compared with the model group, mRNA levels of Cavl.2, Cavl.3, Cav2.1, and Cav2. 3 in brain tissues were decreased, and those of Cav2.2 were increased significantly in the OMT group (P < 0.05). In spinal cord tissues of the OMT group, mRNA levels of Cav1.3 decreased and those of Cav2.1, Cav2.2, and Cav2.3 increased significantly with statistical difference, when compared with those of the model group (P < 0.05). Compared with the sham-operation group, GABA levels in brain tissues decreased in the model group (P < 0.05). Compared with the model group, GABA levels in brain tissues increased in the OMT group (P < 0.05). There was no statistical difference in GABA levels of spinal cord tissues among these groups (P > 0.05). CONCLUSIONS: OMT had analgesic effect on neuropathic pain, which might be probably related to HVDDCs. Cav2.2 might directly affect GABA release. PMID- 26159028 TI - [Acupuncture at Shangjuxu (ST37) to Inhibit Distention of Colon Induced Discharge Reaction of LC: an Experimental Study]. AB - OBJECTIVE: To study possible mechanisms of Shangjuxu (ST37) and the large intestine. METHODS: Totally 40 SD rats were selected. The distension of end colon was used as injured afferent stimulus. Activities of locus coeruleus (LC) neurons were recorded by extracellular microelectrode technique. Shangjuxu (ST37) and Hegu (L14) were needled to observe general features of discharge reactions, distention of colon induced discharge reactions of LC, and its effects on distention of colon induced discharge reactions of LC. RESULTS: Distention of colon could induce incrased discharge of LC neurons by 127.33% +/- 45.48%. But needling at Shangjuxu (ST37) and Hegu (L14) could inhibit this injured response by 38.24% +/- 7.69% and 21.29% +/- 13.16% respectively (all P < 0.01). CONCLUSIONS: Needling at Shangjuxu (ST37) and afferent signals of colon distension converged and interacted with each other. Needling at Shangjuxu (ST37) could significantly inhibit colon distension induced discharge of LC neurons, which might be one of mechanisms for Shangjuxu (ST37) and the large intestine relationship. PMID- 26159029 TI - [Effect of Banxia Qinlian Decoction on Th17/IL-17 Immune Inflammatory Way of Sjogren's Syndrome NOD Model Mice]. AB - OBJECTIVE: To explore the molecular mechanism of exocrine immune inflammatory injury of Sjogren's Syndrome and the intervention of Banxia Qinlian Decoction (BQD). METHODS: Totally 18 female NOD mice were randomly divided into the model group, the positive drug group, and the BQD group, 6 in each group. Six female BALB/c mice were recruited as a blank control group. Mice in the blank control group and the model group were gavaged with deionized water at the daily dose of 0.1 mL/10 g body weight. Tripterygium Tablet was administered by gastrogavage to mice in the positive group at the daily dose of 10 mg/kg. BQD was administered by gastrogavage to mice in the BQD group at the daily dose of 60 g crude drugs/kg. After 12 weeks of medication, mice were sacrificed. Their eyeballs were excised and blood collected. Tissues of bilateral parotids and submandibular glands were kept. mRNA transcriptional levels of IL-17, IL-6, type 3 muscarinic acetylcholine receptors (M3R), aquaporin protein-5 (AQP5) were detected by RT-PCR. Expression levels of M3R and AQP5 protein were detected by Western blot. Protein expression levels of IL-17 and IL-6 were detected by ELISA. RESULTS: Compared with the normal group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly up-regulated in the model group (P < 0.01). Compared with the model group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly down-regulated in the positive drug group and the BQD group with statistical difference (P < 0.01, P < 0.05). Compared with the BQD group, mRNA-transcriptional levels of IL 17, IL-6, and M3R, as well as M3R and AQP5 protein expression levels were significantly down-regulated in the positive drug group (all P < 0.01). CONCLUSION: The molecular mechanism of BQD in inhibiting SS exocrine neurotoxic injury might be possibly related to regulating Th17/IL-17 immune inflammatory way. PMID- 26159030 TI - [Melanin Synthesis was Affected by Extracts of 22 Kinds Chinese Herbs of Acid Taste: an Experi- mental Study]. AB - OBJECTIVE: To confirm the inhibitory effect of Chinese herbs of acid taste on melanin synthesis. METHODS: Active ingredients of 22 kinds Chinese herbs of acid tastes were extracted by alkali extraction and acid precipitation, alcohol extraction, and water extraction, respectively, which was then dispensed into 25.00, 12.50, and 6.25 g/L suspension. Their effects on activities of tyrosinase were detected using mushroom-tyrosinase-DOPA speed oxidation. Their inhibition rates on activities of tyrosinase were respectively compared with inhibition rates of 1.0, 0.5, and 0.1 mmol/L arbutin. RESULTS: The 22 kinds Chinese herbs of acid taste included Cornus Officinalis, Crataegus pinnatifida, dark plum fruit, Schisandra Chinensis, Chaenomeles sinensis Koehne, Reynoutria japonica Houtt, Achyranthes Bidentata, Sanguisorba officinalis L., Semen Ziziphi Spinosae, Herba Ecliptae, blueberry, immature bitter orange, submature bitter orange, Prunus mume Var, Hovenia acerba Lindl., Fructus Mori, Pomegranate Rind, white paeony root, Rosa laevigata Michx., Portulaca oleracea L, Terminalia chebula Retz, Rhus chinensis Mill. Their alkaline extractions showed inhibition to activities of tyrosinase to different degrees except Herba Ecliptae. Of them, the highest inhibition rate (88.49% +/- 9.98%) was got by dark plum fruit at 25 g/L, while the lowest inhibition rate (11.22% +/- 3.36%) was got by immature bitter orange at 6.25 g/L. Their alcohol extractions showed inhibition to activities of tyrosinase to different degrees except Herba Ecliptae. Of them, the highest inhibition rate (75.92% +/- 5.57%) was got by Hovenia acerba Lindl. at 25 g/L, while the lowest inhibition rate (9.60% +/- 1.15%) was got by submature bitter orange at 6.25 g/L. Their water extractions all had inhibition on activities of tyrosinase. Of them, the highest inhibition rate (54.23% +/- 3.56%) was got by Fructus Mori at 25 g/L, while the lowest inhibition rate (10.25% +/- 1.83%) was got by Semen Ziziphi Spinosae at 6.25 g/L. Compared with 1 mmol/L arbutin water solution, alkaline extractions of dark plum fruit, Schisandra Chinensis, Rhus chinensis Mill., Rosa laevigata Michx., blueberry, Chaenomeles sinensis Koehne, Portulaca oleracea L, Fructus Mori, Achyranthes Bidentata, Pomegranate Rind; alcohol extractions of dark plum fruit, Rhus chinensis Mill., Pomegranate Rind, Hovenia acerba Lindl., Crataegus pinnatifida, Achyranthes Bidentata; water extractions of Chaenomeles sinensis Koehne, blueberry, and Fructus Mori at 25 g/L got obviously higher inhibition rates (P < 0.05, P < 0.01). Compared with 0.5 mmol/L arbutin water solution, alcohol extraction of Chaenomeles sinensis Koehne and alcohol extraction of dark plum fruit at 12.5 g/L got obviously higher inhibition rates (P < 0.05, P < 0.01). CONCLUSION: Chinese herbs of acid taste could inhibit melanin synthesis, and its mechanism was related to inhibiting activities of tyrosinase. PMID- 26159031 TI - [Research on Prevention and Treatment of Cardiovascular Disease by Translational Medicine Based Chinese Medicine]. AB - Translational medicine is inevitable in the development of modern medicine, and the uprising concept of translational medicine provides an opportunity for the development of Chinese medicine (CM). Their ideas are well communicated. There are two patterns of researching on CM based on translational medicine: 'literature to bench to bedside' and 'bench to bedside to bench'. CM has her advantages in preventing and treating cardiovascular disease. Effective methods for preventing and treating cardiovascular disease by CM should be further studied based on translational medicine concepts. PMID- 26159032 TI - [Key Points for Design and Evaluation of Clinical Studies in Treating Children's Attention Deficit Hyperactivity Disorder by Chinese Medical New Drugs]. AB - Based on collecting data at home and abroad, we combined clinical practice of scientific researches. We also summarized key points for design and evaluation of clinical studies in treating children's attention deficit hyperactivity disorder by Chinese medical new drugs from objective and design, selection of diagnostic criteria, recruitment and dropping-out of subjects, effectiveness evaluation, safety evaluation, drug combination, and quality control, and so on. We hope to provide reference for design and evaluation of clinical studies by Chinese medical new drugs. PMID- 26159033 TI - [Study on Correlation between Chinese Medical Syndrome Types of HIV/AIDS and Activation of T Lymphocytes]. PMID- 26159034 TI - [Treatment of Chronic Kidney Disease by Modified Huanglian Wendan Decoction: a Case Report]. PMID- 26159035 TI - [Progress of Cancer Related Fatigue]. PMID- 26159036 TI - H-Bonding of Formic Acid with Its Decomposition Products: A Matrix Isolation and Computational Study of the HCOOH/CO and HCOOH/CO2 Complexes. AB - The infrared spectra of formic acid/argon matrix layers deposited after flowing over a drying agent show distinct new bands when compared to matrix layers deposited without going through a drying process. The new bands are assigned as due to a formic acid/carbon monoxide H-bonded complex. Several complexes of HCOOH/CO/H2O and HCOOH/CO2 composition have been characterized in B3LYP and MP2 calculations. Comparison with experimental results indicate that the best agreement is obtained for a 1:1 HCOOH-CO hydrogen bonded complex formed between formic acid and CO originating from the decomposition process HCOOH -> CO + H2O. Spectral and computational evidence is presented for the formation of HCOOH/CO2 complexes as a result of the HCOOH -> CO2 + H2 decomposition path. PMID- 26159038 TI - [SEIP-SERPE-SEOP consensus on musculoskeletal infections in children]. PMID- 26159039 TI - [Ebola in the first person]. PMID- 26159040 TI - Ultrastructural changes associated with myocardial apoptosis, in failing rat hearts induced by volume overload. AB - BACKGROUND: Myocardial apoptosis has been discussed to play a pivotal role in the development and progression of congestive heart failure (CHF). However, recently there is doubt on the evidence of myocardial apoptosis in heart failure as information on ultrastructural changes by electron microscopy is still scarce. This project therefore aimed to detect direct morphological evidence of myocardial apoptosis in an experimental heart failure model. METHOD: Following IRB approval, an aortocaval fistula (ACF) was induced in male Wistar rats using a 16G needle. 28+/-2days following ACF rats were examined by hemodynamic measurements, Western blot, immunofluorescence confocal and electron microscopic analysis. RESULTS: Within 28+/-2days of ACF heart (3.8+/-0.1 vs. 6.6+/-0.3mg/g) and lung (3.7+/-0.2 vs. 6.9+/-0.5mg/g) weight indices significantly increased in the ACF group accompanied by a restriction in systolic (LVEF: 72+/-2 vs. 39+/-3%) and diastolic (dP/dtmin.: -10,435+/-942 vs. -5982+/-745mmHg/s) function (p<0.01). Activated caspase-3 was significantly increased in failing hearts concomitant with mitochondrial leakage of cytochrome c into the cytosol. Finally, electron microscopy of the left ventricle (LV) of ACF rats revealed pronounced ultrastructural changes in >70% of examined cardiomyocytes, such as nuclear chromatin condensation, myofibril loss and disarray, contour irregularities and amorphous dense bodies, mitochondriosis and damaged cell-cell-contacts between cardiomyocytes. CONCLUSIONS: Volume overload induced heart failure is associated with activation of the mitochondrial apoptotic pathway. In addition, electron microscopy of the LV revealed direct ultrastructural evidence of extended myocardial apoptosis in ACF rats. PMID- 26159041 TI - Exosomal clusterin, identified in the pericardial fluid, improves myocardial performance following MI through epicardial activation, enhanced arteriogenesis and reduced apoptosis. AB - BACKGROUND: We recently demonstrated that epicardial progenitor cells participate in the regenerative response to myocardial infarction (MI) and factors released in the pericardial fluid (PF) may play a key role in this process. Exosomes are secreted nanovesicles of endocytic origin, identified in most body fluids, which may contain molecules able to modulate a variety of cell functions. Here, we investigated whether exosomes are present in the PF and their potential role in cardiac repair. METHODS AND RESULTS: Early gene expression studies in 3day infarcted mouse hearts showed that PF induces epithelial-to-mesenchymal transition (EMT) in epicardial cells. Exosomes were identified in PFs from non infarcted patients (PFC) and patients with acute MI (PFMI). A shotgun proteomics analysis identified clusterin in exosomes isolated from PFMI but not from PFC. Notably, clusterin has a protective effect on cardiomyocytes after acute MI in vivo and is an important mediator of TGFbeta-induced. Clusterin addition to the pericardial sac determined an increase in epicardial cells expressing the EMT marker alpha-SMA and, interestingly, an increase in the number of epicardial cells ckit(+)/alpha-SMA(+), 7days following MI. Importantly, clusterin treatment enhanced arteriolar length density and lowered apoptotic rates in the peri infarct area. Hemodynamic studies demonstrated an improvement in cardiac function in clusterin-treated compared to untreated infarcted hearts. CONCLUSIONS: Exosomes are present and detectable in the PFs. Clusterin was identified in PFMI exosomes and might account for an improvement in myocardial performance following MI through a framework including EMT-mediated epicardial activation, arteriogenesis and reduced cardiomyocyte apoptosis. PMID- 26159042 TI - Letter in response to: Elastin fracture and enhanced aortic pressure wave reflection in adult patients with congenital heart disease. PMID- 26159043 TI - Biodiesel production using fatty acids from food industry waste using corona discharge plasma technology. AB - This article aims to describe an alternative and innovative methodology to transform waste, frying oil in a potential energy source, the biodiesel. The biodiesel was produced from fatty acids, using a waste product of the food industry as the raw material. The methodology to be described is the corona discharge plasma technology, which offers advantages such as acceleration of the esterification reaction, easy separation of the biodiesel and the elimination of waste generation. The best conditions were found to be an oil/methanol molar ratio of 6:1, ambient temperature (25 degrees C) and reaction time of 110 min and 30 mL of sample. The acid value indicates the content of free fatty acids in the biodiesel and the value obtained in this study was 0.43 mg KOH/g. Peaks corresponding to octadecadienoic acid methyl ester, octadecanoic acid methyl ester and octadecenoic acid methyl ester, from the biodiesel composition, were identified using GC-MS. A major advantage of this process is that the methyl ester can be obtained in the absence of chemical catalysts and without the formation of the co-product (glycerin). PMID- 26159044 TI - Urban mining as a contribution to the resource strategy of the Canton of Zurich. AB - Urban mining is increasingly being recognised as an important component of resource strategies of public authorities, not only because it contributes to environmental protection, but also because it is a source of valuable recyclable materials. We demonstrate that the sustainable livelihoods (SL) framework can be used for public policy making in waste management by presenting the approach and experiences of a review study termed 'urban mining potential analysis' and its application to antimony, copper, gypsum, gold and rare earth elements. This article uses the rare earth element (REE) group to illustrate and present an overview over information and knowledge gaps concerning urban mining. The analysis shows that rare earth element recycling can be more environmentally friendly than primary production, particularly if the latter comes from countries with weak enforcement of environmental legislation. On the other hand REE recycling often cannot compete with large scale primary production because market prices do not reflect the social and environmental impacts of production, and because the avoided impacts of waste decontamination and reduced waste production are not considered. The urban mining potential analysis can be used to support decision making and the setting of priorities for future research and public action. The findings of the study and expert opinions based thereon contribute to the selection of measures and the formulation of public waste management and resource strategies in general. PMID- 26159045 TI - Risk of second primary malignancies and survival of adult patients with polycythemia vera: A United States population-based retrospective study. AB - Although the median survival in polycythemia vera (PV) is 14 years, mortality is higher than in an age- and sex-matched population. This study included 3941 PV patients diagnosed between 2000-2012 from Surveillance, Epidemiology and End Results (SEER) 13 registry to determine 5-year survival and the incidence of second primary malignancies (SPM). The actuarial 5 year survival in the overall cohort was 79.5%. The cumulative incidence of SPM was 13.1% at 10 years. SPMs occurred at a standardized incidence ratio (SIR) of 1.29 (95% CI = 1.16-1.43; p < 0.001) with an absolute excess risk (AER) of 42.49 per 10 000 population. A significantly higher risk was noted for acute myeloid leukemia (SIR = 12.24; 95% CI = 8.17-17.8; p-value < 0.001) and chronic myeloid leukemia (SIR = 10.66; 95% CI = 3.75-19.6; p-value < 0.001). Patients with PV are at a high risk of SPM and leukemic transformation, which may compromise long-term survival. PMID- 26159046 TI - A single-institution retrospective analysis of outcomes for stage I-II primary mediastinal large B-cell lymphoma treated with immunochemotherapy with or without radiotherapy. AB - As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes. PMID- 26159047 TI - Myelodysplastic syndromes spatial clusters in disease etiology and outcome. AB - The myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders. This study aims to advance the use of spatial modeling in disease etiology and monitoring based on reports on a large population (n = 984) of MDS patients diagnosed in the Eastern United States. The spatial MDS clustering was analyzed using SaTScan, and patient clinical characteristics were analyzed using logistic regression and Cox hazards models adjusting for covariates. One main and five secondary spatial clusters (p-value < 10-17-10-7) were identified. Patients living in high vs. low MDS incidence clusters tended to be older (ORadj = 1.04 [1.004, 1.07]) and smokers (ORadj = 2.9 [1.1, 7.4]). Mortality was associated with hemoglobin (HRadj = 0.7 [0.5, 0.9]), neutrophils (HRadj = 0.7 [0.6, 0.96]), platelets (HRadj = 0.5 [0.4, 0.7]), and blast (HRadj = 1.4 [1.1, 1.8]), but not clusters. The results suggest large geographic variations in MDS incidence rates. The biological aggressiveness of the disease is unlikely to be associated with its spatial distribution. PMID- 26159048 TI - Enhanced analgesic activity by cyclodextrins - a systematic review and meta analysis. AB - INTRODUCTION: Analgesics can be ineffective in treating some types of pain, hence, improved drug delivery systems could optimize their efficacy. AREA COVERED: The authors conducted a systematic review to evaluate the analgesic activity of compounds complexed in cyclodextrins, analyzing whether these complexes improved analgesic efficacy. The search terms 'analgesics', 'cyclodextrins' and 'drug effects' were used to retrieve articles in SCOPUS, PUBMED and EMBASE. A total of 22 papers were identified. In the clinical studies, there was greater efficacy in the complexed drug when compared with control groups, with differences ranging from 25 to 83%. Through a meta-analysis, the preclinical studies showed that the complexed drug had a significantly (p < 0.01) greater effect than the non-complexed drug. EXPERT OPINION: The use of cyclodextrins can improve the efficacy of analgesic compounds, and they are an important tool in the search for greater analgesic effect. They may also be a way to reduce the therapeutic doses, and hence increasing the potential of the drug. PMID- 26159049 TI - Role of Steroids in Hyperexcitatory Adverse and Anesthetic Effects of Sevoflurane in Neonatal Rats. AB - Recent studies have demonstrated that long-term developmental effects of neonatal anesthesia were more prominent in males. We tested whether steroids, in general, and sex steroids, in particular, are involved in the mediation of sevoflurane caused paradoxical cortical seizures during the early postnatal period. METHODS: Cortical electroencephalograms, hippocampal synaptic activity, serum levels of steroids and the loss of the righting reflex (LORR), a marker of anesthetic effect, were measured on postnatal days 4-6 in Sprague Dawley rats of both genders exposed to 2.1% sevoflurane. RESULTS: Episodes of seizures, persistent spikes in electroencephalograms and increases in serum corticosterone were similar in both genders. In the order of increasing potency, the corticosteroid receptor antagonist RU 28318, the estradiol receptor antagonist ICI 182780 and the estradiol synthesis inhibitor formestane decreased sevoflurane-induced seizures. Exogenous estradiol increased sevoflurane-caused seizures, spikes and serum levels of corticosterone. These estradiol-enhanced seizures and spikes were depressed by ICI 182780 and the NKCC1 inhibitor, bumetanide, while RU 28318 decreased seizures only. In hippocampal CA1 neurons, estradiol increased the amplitude, rise time and area under the curve of gamma-aminobutyric acid type A receptor (GABAAR)-mediated miniature postsynaptic currents. Exogenous estradiol shortened, while ICI 182780 and formestane lengthened the time needed for sevoflurane to induce LORR. CONCLUSION: These findings provide evidence for gender-independent acute electroencephalographic effects of sevoflurane at this age. Corticosterone and estradiol are involved in the mediation of sevoflurane induced seizures. Estradiol, but not corticosterone, also contributes to sevoflurane-caused spikes, by enhancing GABAAR-mediated excitation in the cortex. By increasing GABAAR-mediated inhibition in more mature caudal regions of the brain, estradiol contributes to sevoflurane-induced LORR. PMID- 26159050 TI - da Vinci and Open Radical Prostatectomy: Comparison of Clinical Outcomes and Analysis of Insurance Costs. AB - PURPOSE: To assess clinical outcomes and reimbursement costs of open and robotic assisted radical prostatectomies in Germany. METHODS: Perioperative data of 499 open (2003-2006) and 932 (2008-2010) robotic-assisted radical prostatectomies as well as longitudinal reimbursement costs of an anonymized health insurance research database from Germany containing data of patients who underwent robotic assisted or open radical prostatectomy were retrospectively analysed in a single centre study. RESULTS: Significantly better outcomes after robotic-assisted vs. open prostatectomy were observed in regards to positive surgical margins (13.3 vs. 22.4%; p < 0.0001), intraoperative transfusions (0.1 vs. 2.6%; p < 0.0001), hospitalization (8.7 vs. 15.2 days; p < 0.0001) and duration of catheter (6.6 vs. 12.8 days; p < 0.0001). Operating time was significantly longer with robotic assisted radical prostatectomy when compared to open surgery (184.4 vs. 128.0 min; p < 0.0001), while intraoperative complications showed a similar occurrence between both groups. Significant fewer postoperative complications were observed after robotic-assisted radical prostatectomy (26.5 vs. 42.5%; p < 0.0001) and rate of re-admission was lower for the robotic patients (13.6 vs. 19.4%; p = 0.0050). While insurance costs were higher in the 2 years before radical prostatectomy for the patients who underwent a robotic procedure (4,241.60 vs. 3,410.23 ?; p = 0.202), additive costs of care of the year of surgery plus the 2 following years were less for the robotic cohort when compared to the costs incurred by the open group (21,673.71 vs. 24,512.37 ?; p = 0.1676). CONCLUSIONS: The observed clinical advantages of robotic-assisted radical prostatectomy seem to result in reduced health insurance cost postoperatively when compared to open surgery. This should be taken into consideration regarding reimbursement and implementation of a clinically superior method. PMID- 26159051 TI - Autocrine amplification of immature myeloid cells by IL-6 in multiple myeloma infiltrated bone marrow. AB - Multiple myeloma (MM) invariably develops in the bone marrow (BM), indicating the strong requirement of this tumor for the peculiar BM microenvironment, rich in cytokine and hematopoietic precursor cells. Interleukin-6 (IL-6) and a proliferation inducing ligand (APRIL) are key cytokines implicated in MM development. Here, we show that MM cells changed the hematopoietic microenvironment early upon BM infiltration by strongly downregulating hematopoietic precursor cells from all lineages except myeloid precursor cells. Myeloid precursor cells constituted a major source of APRIL in MM-infiltrated BM, and their proliferative response to IL-6 upregulation explained their relative resistance to MM infiltration. The osteolytic molecule receptor activator of NF kB ligand (RANK-L) expressed by MM cells started this myeloid proliferation by inducing in a contact-dependent manner IL-6 production by myeloid precursor cells themselves. Taken together, our data demonstrate that MM cells do not simply displace hematopoietic cells upon BM infiltration, but rather selectively modulate the BM microenvironment to preserve a pool of high APRIL-producing myeloid precursor cells. Our data also identify a positive regulation of APRIL by IL-6 in myeloid precursor cells. PMID- 26159052 TI - [Serious and unexpected complications of benign prostatic obstruction surgery: Results of the LUTS Committee survey from urologists of the French Urological Association]. AB - PURPOSE: Rare and severe complications of benign prostatic hyperplasia (BPH) surgery are poorly documented in the literature. Our purpose was to make an inventory of severe and unexpected complications of BPH faced by urologists of the French Association of Urology (AFU). MATERIAL AND METHODS: A declarative 13 question survey was sent by e-mail 2 months before the 108th French Congress of Urology to the urologist's members of the AFU. Complications were split in complications due to material and complications directly related to the surgery. RESULTS: Overall, 216 (16.2%) urologists surveyed but only 85 forms were usable. Complications related to the material was divided into: excessive temperature of the serum irrigation leading to urethral and bladder burns (n=5), material default leading to interruption of the procedure (n=1) or incomplete hemostasis (n=2) and endoscope rupture (n=1). Peroperative complications related to surgery were divided into surgical complications: haemorrhage (n=7), urethral wounds (n=6), perforation and/or explosion (n=16), rectal wounds (n=11), obstructive renal failure (n=1); and medical complications: TURP syndrome (n=2), cardiovascular (n=5) and septic shock (n=6). CONCLUSION: This is the first French declarative study having allowed the identification of severe and unexpected complications of BPH surgery. The recorded occurred complications were very eclectic and secondary to all types of techniques used. PMID- 26159053 TI - [Renal transplantation using a Maastricht category III non-heartbeating donor: First French experience and review of the literature]. AB - In 2015, Annecy Hospital was the first French hospital to perform non heartbeating organ donation from a Maastricht category III donor (patient awaiting cardiac arrest after withdrawal of treatment). Non-heartbeating organ donation (NHBD), performed in France since 2006, had initially excluded this category, due to ethical questions concerning end of life and treatment withdrawal, as well as technical specificities linked to this procedure. Grenoble University Hospital and Edouard-Herriot Hospital in Lyon then performed the first kidney transplants, with satisfactory outcomes in both recipients. This article presents the details and results of this new experience, challenging both on a deontological and organizational level. Functional outcomes of kidney grafts from NHBD are now well known in the literature and confirm their benefit for patients, with similar results to those from heartbeating donors (HBD). International experiences concerning specifically Maastricht category III NHBD are encouraging and promising. PMID- 26159054 TI - [Urinary incontinence in non-professional female marathon runners]. AB - OBJECTIVE: To determine the prevalence of urinary incontinence within a population of female recreational runners during a marathon. METHODS: Observational study carried on a marathon from the analysis of questionnaire handed to the participants before the beginning of the marathon. The questionnaire was handed to 800 participants and among them, 517 (64.6%) agreed to fill it. Among the participants, 268 (52.4%) were marathon runners and 243 (47.5%) were relay runners. RESULTS: Mean age of the runners was 41.1 (+/-9.7), 479 (93.7%) of them were caucasian, mean body mass index was 20,7 (+/-1.9) kg/m(2) and 173 (34%) were nulliparous. Among responders, 157 (30.7%) runners declared to have urinary incontinence symptoms (any circumstances). Among 157 runners who declared an urinary incontinence, 83 (52,9%) presented with urinary leaks during the running. In half of the cases, these urinary leaks usually arose at the end of race. Urinary incontinence during coughing, sneezing or laughing was reported by 96/517 (18,5%) women. The prevalence of urge urinary incontinence was 63/517 (12%). Concerning the frequency of urinary incontinence, 39/517 (7.5%) women reported at least once weekly. For urinary incontinence bother, scores on the Visual Analogue Scale (VAS 0 to 100) was 1.6 (+/-1.7). CONCLUSION: In this series, the prevalence of urinary incontinence was 30.7% within a population of female recreational runners. This rate seems to be similar to the current prevalence in the general population. PMID- 26159055 TI - Probing the Surface Hydration of Nonfouling Zwitterionic and PEG Materials in Contact with Proteins. AB - Zwitterionic polymers and poly(ethylene glycol) (PEG) have been reported as promising nonfouling materials, and strong surface hydration has been proposed as a significant contributor to the nonfouling mechanism. Better understanding of the similarity and difference between these two types of materials in terms of hydration and protein interaction will benefit the design of new and effective nonfouling materials. In this study, sum frequency generation (SFG) vibrational spectroscopy was applied for in situ and real-time assessment of the surface hydration of the sulfobetaine methacrylate (SBMA) and oligo(ethylene glycol) methacrylate (OEGMA) polymer brushes, denoted as pSBMA and pOEGMA, in contact with proteins. Whereas a majority of strongly hydrogen-bonded water was observed at both pSBMA and pOEGMA surfaces, upon contact with proteins, the surface hydration of pSBMA remained unaffected, but the water ordering at the pOEGMA surface was disturbed. The effects of free sulfobetaine, free PEG chains with two different molecular weights, and PEG coated gold nanoparticles on the surface hydration of proteins were investigated. The results indicated that free sulfobetaine could strengthen the protein hydration layer, but free PEG chains greatly disrupt the protein hydration layer and likely directly interact with the protein molecules. In contrast to free PEG, the PEG chains anchored on the nanoparticles behave similarly to the pOEGMA surface and could induce strong hydrogen bonding of the water molecules at the protein surfaces. PMID- 26159056 TI - Very early osteoarthritis changes sensitively fluid flow properties of articular cartilage. AB - In this study, fibril-reinforced poroelastic (FRPE) modeling was used for rabbit knee after anterior cruciate ligament transection (ACLT) to assess how the mechanical properties of collagen, proteoglycans, and fluid in articular cartilage change in early osteoarthritis, and how site-specific these changes are. Unilateral ACLT was performed in eight skeletally mature, female New Zealand white rabbits. A separate control (CTRL) group consisted of knee joints of five non-operated rabbits. Animals were sacrificed at four weeks after ACLT and cartilage-on-bone samples from femoral groove, medial and lateral femoral condyles, and tibial plateaus were harvested. A stress-relaxation protocol in indentation geometry was applied and the FRPE model was fitted to the experimental force-time curve by minimizing the mean absolute error between experiment and simulation. The optimized parameters were: fibril network modulus (Ef), representing the collagen network; non-fibrillar matrix modulus (Enf), representing the PG matrix; and permeability (k), representing fluid flow. Permeability was increased significantly in the ACLT group compared to the CTRL group knees at all sites except for the medial tibial plateau. ACLT also caused a decrease in the Ef at all sites except for the medial and lateral tibial plateaus. The Enf of the ACLT group knees was altered only for the lateral femoral condyle. The results of this study suggest that early osteoarthritis primarily affects cartilage permeability and impairs the collagen network stiffness in a site-specific manner. These findings from early osteoarthritis indicate that fluid flow velocity in articular cartilage may change prior to quantifiable structural alterations in the tissue. PMID- 26159057 TI - Vertical accelerator device to apply loads simulating blast environments in the military to human surrogates. AB - The objective of the study was to develop a simple device, Vertical accelerator (Vertac), to apply vertical impact loads to Post Mortem Human Subject (PMHS) or dummy surrogates because injuries sustained in military conflicts are associated with this vector; example, under-body blasts from explosive devices/events. The two-part mechanically controlled device consisted of load-application and load receiving sections connected by a lever arm. The former section incorporated a falling weight to impact one end of the lever arm inducing a reaction at the other/load-receiving end. The "launch-plate" on this end of the arm applied the vertical impact load/acceleration pulse under different initial conditions to biological/physical surrogates, attached to second section. It is possible to induce different acceleration pulses by using varying energy absorbing materials and controlling drop height and weight. The second section of Vertac had the flexibility to accommodate different body regions for vertical loading experiments. The device is simple and inexpensive. It has the ability to control pulses and flexibility to accommodate different sub-systems/components of human surrogates. It has the capability to incorporate preloads and military personal protective equipment (e.g., combat helmet). It can simulate vehicle roofs. The device allows for intermittent specimen evaluations (x-ray and palpation, without changing specimen alignment). The two free but interconnected sections can be used to advance safety to military personnel. Examples demonstrating feasibilities of the Vertac device to apply vertical impact accelerations using PMHS head-neck preparations with helmet and booted Hybrid III dummy lower leg preparations under in-contact and launch-type impact experiments are presented. PMID- 26159058 TI - Intensity and generalization of treadmill slip training: High or low, progressive increase or decrease? AB - The purpose of this study was to investigate the efficacy of different treadmill slip training protocols on the transfer of reactive and proactive control of center of mass stability to a novel, over-ground slip. Four training protocols were investigated: high-intensity (HI; acceleration of all treadmill slips=12m/s(2)), low-intensity (LO; acceleration of all treadmill slips=6m/s(2)), progressively increasing intensity (INCR; acceleration of treadmill slips increasing from 6m/s(2) to 12m/s(2) over the course of training), and progressively decreasing intensity (DECR; acceleration of treadmill slips decreasing from 12m/s(2) to 6m/s(2) over the course of training). From a pool of 36 young subjects, nine were randomly assigned to each training protocol (HI, LO, INCR, and DECR). In each protocol, subjects underwent a series of 24 treadmill slips before they experienced a novel slip during over-ground walking. Measures from these subjects were compared across groups and to data from control subjects (CTRL, n=9) who had experienced a novel over-ground slip without treadmill training as part of a previous experiment. The results showed that treadmill slip training improved balance control on over-ground slip and had a larger effect on subjects' reactive control of stability (44.3%) than on proactive control (27.1%) in comparison with the CTRL group. HI yielded stronger generalization than LO, while INCR was only marginally better than DECR. Finally, the group means of stability displayed a clear ascending order from CTRL, LO, DECR, INCR, to HI. PMID- 26159059 TI - Role of gradients in vocal fold elastic modulus on phonation. AB - New studies show that the elastic properties of the vocal folds (VFs) vary locally. In particular strong gradients exist in the distribution of elastic modulus along the length of the VF ligament, which is an important load-bearing constituent of the VF tissue. There is further evidence that changes in VF health are associated with alterations in modulus gradients. The role of VF modulus gradation on VF vibration and phonation remains unexplored. In this study the magnitude of the gradient in VF elastic modulus is varied, and sophisticated computational simulations are performed of the self-oscillation of three dimensional VFs with realistic modeling of airflow physical properties. Results highlight that phonation frequency, characteristic modes of deformation and phase differences, glottal airflow rate, spectral-width of vocal output, and glottal jet dynamics are dependent on the magnitude of VF elastic modulus gradation. The results advance the understanding of how VF functional gradation can lead to perceptible changes in speech quality. PMID- 26159060 TI - Structural and mechanical properties of the human Achilles tendon: Sex and strength effects. AB - Tendons are elastic structures that connect muscle to the skeletal system and transmit force relative to the amount of stretch they experience. The mechanical properties of human tendons are difficult to measure non-invasively, so generic values are often assumed in musculoskeletal models to represent all subjects. We aimed to determine the in vivo mechanical properties of the human Achilles tendon by calculating tendon stiffness and resting length in 10 male and 10 female trained cyclists. B-mode ultrasound coupled with motion capture was used to track the tendon lengths for the medial and lateral gastrocnemii concurrently with ankle torque measurements during ramped isometric contractions. Achilles tendon stiffness was calculated as the slope of the linear portion of the force-length curve, and this was extrapolated to zero force to yield the tendon resting length. Average Achilles tendon stiffness was 201.8 +/- 5.9 N mm(-1). There was no difference in Achilles tendon stiffness or maximum isometric force between males and females, however tendon stiffness varied between individuals. The resting lengths of the MG and LG tendon were 0.209 +/- 0.002 m and 0.222 +/- 0.002 m respectively, and regression models determined that shank length was the best predictor of resting tendon length. Our results indicate that Achilles tendon stiffness varies with muscle strength and not sex. The variability in Achilles tendon stiffness between subjects support the need for experimentally measured subject-specific tendon properties as input parameters to improve the accuracy of musculoskeletal models. PMID- 26159061 TI - A novel assessment technique for measuring ankle orientation and stiffness. AB - The measurement of ankle orientation and stiffness can provide insight into improvements and allows for effective monitoring during a rehabilitation program. Existing assessment techniques have a variety of limitations. Dynamometer based methods rely on manual manipulation. The use of torque meter is usually for single degree-of-freedom (DOF) devices. This study proposes a novel ankle assessment technique that can be used for multiple DOFs devices working in both manual and automatic modes using the position sensor and the multi-axis load cell. As a preliminary evaluation, an assessment device for ankle dorsiflexion and plantarflexion was constructed. Nine subjects participated to evaluate the effectiveness of the assessment device in determining ankle orientation and stiffness. The measured ankle orientation was consistent with that from the NDI Polaris optical tracking system. The measured ankle torque and stiffness compared well with published data. The test-retest reliability was high with intraclass correlation coefficient (ICC2, 1) values greater than 0.846 and standard error of measurement (SEM) less than 1.38. PMID- 26159062 TI - A comparison of blood loss during the Halal slaughter of lambs following Traditional Religious Slaughter without stunning, Electric Head-Only Stunning and Post-Cut Electric Head-Only Stunning. AB - Blood lost at exsanguination during the Halal slaughter of lambs was compared between the slaughter methods of Traditional Religious Slaughter without stunning (TRS), Electric Head-Only Stunning (EHOS) and Post-Cut Electric Head-Only Stunning (PCEHOS). Two protocols were examined, Experimental (80 lambs) and Commercial (360 lambs), assessing varying periods of animal orientation during the 4 min bleeding process (upright orientation before vertical hanging). Live weight, blood weight (Experimental only), carcass weights and by-product weights were recorded. The Experimental protocol highlighted an increase in blood loss at 60s in EHOS and PCEHOS compared to TRS (P<0.001) but by 90 s there was no significant difference. A post-slaughter change in animal orientation from an upright to a vertical hanging position aided the amount of blood loss. The bleeding of lambs is largely completed by 2 min. There were no significant differences (P>0.05) in final blood loss between treatments. This research was undertaken to inform discussion on the merits of different slaughter methods compatible with Halal requirements. PMID- 26159063 TI - Nanotechnology in cosmetics. AB - Nanomaterials are being used in cosmetic products for various effects. However, their use also raises potential safety concerns. Some of these concerns can be addressed by determining the type of nanomaterials used, as well as stability, potential for skin absorption, route of exposure, and how they are formulated in cosmetic products. There has been considerable effort internationally to harmonize approaches in order to address definitional issues and safety concerns related to the use of nanomaterials in cosmetic products. PMID- 26159064 TI - Glutathione Is the Resolving Thiol for Thioredoxin Peroxidase Activity of 1-Cys Peroxiredoxin Without Being Consumed During the Catalytic Cycle. AB - AIMS: A three-step catalytic cycle is common to all peroxiredoxins (Prxs), despite structural and kinetic differences. The second step in 1-Cys type Prxs is a matter of debate since they lack an additional cysteine to play the resolving role, as happens with the 2-Cys Prxs. The aim of this study was to elucidate the role of glutathione (GSH) in the thioredoxin-dependent peroxidase activity of Saccharomyces cerevisiae mitochondrial Prx1p, a 1-Cys type Prx. RESULTS: The peroxidatic Cys91 residue of two Prx1p peptides can be linked by a disulfide, which can be reduced by thioredoxin and by GSH (Km=6.1 MUM). GSH forms a mixed disulfide with the peroxidatic cysteine spontaneously in vitro and in vivo. Mitochondrial Trx3p deglutathionylates Prx1p without formation of GSSG so that GSH is not consumed in the process. The structural unit of native Prx1p is a dimer whose subunits are not covalently linked, but a hexameric assembly of three disulfide-bound dimers can also be formed. INNOVATION: GSH is presented as a protective cofactor of Prx1p, which is not consumed during the peroxidase reaction, but provides a robust mechanism as the resolving cysteine and efficiently prevents Prx1p overoxidation. GSH exerts these roles at concentrations well below those commonly considered necessary for its antioxidant and redox buffering functions. CONCLUSION: A 1-Cys peroxide scavenging mechanism operates in yeast mitochondria involving an autonomous glutathione molecule and the thioredoxin system, which could have universal validity. Prx1p is fairly well protected from overoxidation, questioning its role in a floodgate mechanism for H2O2 signaling. PMID- 26159066 TI - Influence of water on the homogeneous gas-phase formation mechanism of polyhalogenated dioxins/furans from chlorinated/brominated phenols as precursors. AB - Water is of great chemical importance due to its ability to form hydrogen bond. Polyhalogenated dibenzo-p-dioxin/benzofurans (PHDD/Fs) are notorious due to their persistence, bioaccumulation and extremely high toxicity. Water is ubiquitous, and a deep knowledge of its influence on the formation mechanism of PHDD/Fs is necessary. This work investigated the influence of water on the homogeneous gas phase formation of PHDD/Fs from halogenated phenols (HPs) as precursors by using quantum chemical calculations with the aid of the MPWB1K theoretical approach in connection with the 6-31+G(d,p) and 6-311+G(3df,2p) basis sets. The schematic energy profile in the presence of water was constructed and compared with the situation without water. This study reveals for the first time that the introduction of water promotes the formation of halogenated phenoxy radicals (HPRs) from the H abstraction reactions of HPs with atomic H and OH radicals by lowering the reaction energy barriers and opening new low-energy pathways. Another intriguing finding of this work is that the inclusion of a water molecule produces a catalytic effect on the H-shift step involved in the formation of PHDFs and thus their formation potential is enhanced. PMID- 26159065 TI - Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. AB - BACKGROUND: Optimum management strategies for patients with advanced non-small cell lung cancer (NSCLC) with acquired resistance to EGFR tyrosine-kinase inhibitors are undefined. We aimed to assess the efficacy and safety of continuing gefitinib combined with chemotherapy versus chemotherapy alone in patients with EGFR-mutation-positive advanced NSCLC with acquired resistance to first-line gefitinib. METHODS: The randomised, phase 3, multicentre IMPRESS study was done in 71 centres in 11 countries in Europe and the Asia-Pacific region. Eligible patients were aged at least 18 years with histologically confirmed, chemotherapy-naive, stage IIIB-IV EGFR-mutation-positive advanced NSCLC with previous disease control with first-line gefitinib and recent disease progression (Response Evaluation Criteria in Solid Tumors version 1.1). Participants were randomly assigned (1:1) by central block randomisation to oral gefitinib 250 mg or placebo once daily in tablet form; randomisation did not include stratification factors. All patients also received the platinum-based doublet chemotherapy cisplatin 75 mg/m(2) plus pemetrexed 500 mg/m(2) on the first day of each cycle. After completion of a maximum of six chemotherapy cycles, patients continued their randomly assigned treatment until disease progression or another discontinuation criterion was met. All study investigators and participants were masked to treatment allocation. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The study has completed enrolment, but patients are still in follow-up for overall survival. This trial is registered with ClinicalTrials.gov, number NCT01544179. FINDINGS: Between March 29, 2012, and Dec 20, 2013, 265 patients were randomly assigned: 133 to the gefitinib group and 132 to the placebo group. At the time of data cutoff (May 5, 2014), 98 (74%) patients had disease progression in the gefitinib group compared with 107 (81%) in the placebo group (hazard ratio 0.86, 95% CI 0.65-1.13; p=0.27; median progression-free survival 5.4 months in both groups [95% CI 4.5-5.7 in the gefitinib group and 4.6-5.5 in the placebo group]). The most common adverse events of any grade were nausea (85 [64%] of 132 patients in the gefitinib group and 81 [61%] of 132 patients in the placebo group) and decreased appetite (65 [49%] and 45 [34%]). The most common adverse events of grade 3 or worse were anaemia (11 [8%] of 132 patients in the gefitinib group and five [4%] of 132 patients in the placebo group) and neutropenia (nine [7%] and seven [5%]). 37 (28%) of 132 patients in the gefitinib group and 28 (21%) of 132 patients in the placebo group reported serious adverse events. INTERPRETATION: Continuation of gefitinib after radiological disease progression on first-line gefitinib did not prolong progression-free survival in patients who received platinum-based doublet chemotherapy as subsequent line of treatment. Platinum-based doublet chemotherapy remains the standard of care in this setting. FUNDING: AstraZeneca. PMID- 26159067 TI - Formation of mixed halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs). AB - This contribution investigates mechanistic and kinetic parameters pertinent to formation of mixed dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) from the condensation reactions involving 2-chlorophenoxy (2-CPxy) and 2-bromophenoxy (2 BPxy) radicals. Keto-ether structures act as direct intermediates for the formation of DD, 1-MCDD, 1-MBDD, 1-B,6-CDD and 1-B,9-CDD molecules. Likewise, diketo adducts initiate the formation of 4-MCDF, 4-MBDF and 4-B,6-CDF compounds through interconversion and rearrangement reactions. As formation mechanisms of halogenated dibenzo-p-dioxins and dibenzofurans from precursors of brominated and chlorinated phenols are insensitive to substitution at meta and para sites, our mechanistic and kinetic analysis of reactions involving 2-BPxy and 2-CPxy should also apply to higher halogenated phenoxy radicals. PMID- 26159068 TI - Shear Wave Elastography (SWE): An Analysis of Breast Lesion Characterization in 83 Breast Lesions. AB - Qualitative and quantitative shear wave elastography (SWE) criteria were assessed to differentiate between malignant and benign breast lesions. This prospective study included 83 lesions. SWE features measured included maximal stiffness values inside the lesion (E(lesion)) and in the peri-lesion area (E(perilesion)) and ratio values (R(lesion) and R(perilesion)) according to the formula E(lesion) or E(perilesion)/E(fat), with E(fat) corresponding to normal fatty tissue. We compared ultrasonography (B-mode), SWE and histologic sizes. With qualitative and quantitative SWE analysis, sensitivity was 94% and specificity 73%. Malignant lesions appeared more heterogeneous, with higher stiffness and ratio values than benign lesions (p < 0.001). For malignant lesions, SWE size was better correlated to histologic size than B-mode size. Using benign SWE signs to selectively downgrade category 4a and 4b lesions, the specificity improved from 13% to 51% without loss in sensitivity (100%) compared to ultrasound. PMID- 26159069 TI - The Bacterial Phosphotransferase System: New Frontiers 50 Years after Its Discovery. AB - In 1964, Kundig, Ghosh and Roseman reported the discovery of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), which they subsequently proposed might catalyze sugar transport as well as sugar phosphorylation. What we have learned in the 50 years since its discovery is that, in addition to these primary functions, the PTS serves as a complex protein kinase system that regulates a wide variety of transport, metabolic and mutagenic processes as well as the expression of numerous genes. Recent operon- and genome sequencing projects have revealed novel PTS protein-encoding genes, many of which have yet to be functionally defined. The current picture of the PTS is that of a complex system with ramifications in all aspects of cellular physiology. Moreover, its mosaic evolutionary history is unusual and intriguing. The PTS can be considered to serve many prokaryotes in capacities of communication and coordination, as do the nervous systems of animals. PMID- 26159070 TI - PTS 50: Past, Present and Future, or Diauxie Revisited. AB - PAST: The title 'PTS 50 or The PTS after 50 years' relies on the first description in 1964 of the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system (PTS) by Kundig, Gosh and Roseman [Proc Natl Acad Sci USA 1964;52:1067-1074]. The system comprised proteins named Enzyme I, HPr and Enzymes II, as part of a novel PTS for carbohydrates in Gram-negative and Gram-positive bacteria, whose 'biological significance remained unclear'. In contrast, studies which would eventually lead to the discovery of the central role of the PTS in bacterial metabolism had been published since before 1942. They are primarily linked to names like Epps and Gale, J. Monod, Cohn and Horibata, and B. Magasanik, and to phenomena like 'glucose effects', 'diauxie', 'catabolite repression' and carbohydrate transport. PRESENT: The pioneering work from Roseman's group initiated a flood of publications. The extraordinary progress from 1964 to this day in the qualitative and in vitro description of the genes and enzymes of the PTS, and of its multiple roles in global cellular control through 'inducer exclusion', gene induction and 'catabolite repression', in cellular growth, in cell differentiation and in chemotaxis, as well as the differences of its functions between Gram-positive and Gram-negative bacteria, was one theme of the meeting and will not be treated in detail here. FUTURE: At the 1988 Paris meeting entitled 'The PTS after 25 years', Saul Roseman predicted that 'we must describe these interactions [of the PTS components] in a quantitative way [under] in vivo conditions'. I will present some results obtained by our group during recent years on the old phenomenon of diauxie by means of very fast and quantitative tests, measured in vivo, and obtained from cultures of isogenic mutant strains growing under chemostat conditions. The results begin to hint at the problems relating to future PTS research, but also to the 'true science' of Roseman. PMID- 26159071 TI - PTS-Mediated Regulation of the Transcription Activator MtlR from Different Species: Surprising Differences despite Strong Sequence Conservation. AB - The hexitol D-mannitol is transported by many bacteria via a phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS). In most Firmicutes, the transcription activator MtlR controls the expression of the genes encoding the D mannitol-specific PTS components and D-mannitol-1-P dehydrogenase. MtlR contains an N-terminal helix-turn-helix motif followed by an Mga-like domain, two PTS regulation domains (PRDs), an EIIB(Gat)- and an EIIA(Mtl)-like domain. The four regulatory domains are the target of phosphorylation by PTS components. Despite strong sequence conservation, the mechanisms controlling the activity of MtlR from Lactobacillus casei, Bacillus subtilis and Geobacillus stearothermophilus are quite different. Owing to the presence of a tyrosine in place of the second conserved histidine (His) in PRD2, L. casei MtlR is not phosphorylated by Enzyme I (EI) and HPr. When the corresponding His in PRD2 of MtlR from B. subtilis and G. stearothermophilus was replaced with alanine, the transcription regulator was no longer phosphorylated and remained inactive. Surprisingly, L. casei MtlR functions without phosphorylation in PRD2 because in a ptsI (EI) mutant MtlR is constitutively active. EI inactivation prevents not only phosphorylation of HPr, but also of the PTS(Mtl) components, which inactivate MtlR by phosphorylating its EIIB(Gat)- or EIIA(Mtl)-like domain. This explains the constitutive phenotype of the ptsI mutant. The absence of EIIB(Mtl)-mediated phosphorylation leads to induction of the L. caseimtl operon. This mechanism resembles mtlARFD induction in G. stearothermophilus, but differs from EIIA(Mtl)-mediated induction in B. subtilis. In contrast to B. subtilis MtlR, L. casei MtlR activation does not require sequestration to the membrane via the unphosphorylated EIIB(Mtl) domain. PMID- 26159073 TI - Fucose-Mediated Transcriptional Activation of the fcs Operon by FcsR in Streptococcus pneumoniae. AB - In this study, we explore the impact of fucose on the transcriptome of S. pneumoniae D39. The expression of various genes and operons, including the fucose uptake PTS and utilization operon (fcs operon) was altered in the presence of fucose. By means of quantitative RT-PCR and beta-galactosidase analysis, we demonstrate the role of the transcriptional regulator FcsR, present upstream of the fcs operon, as a transcriptional activator of the fcs operon. We also predict a 19-bp putative FcsR regulatory site (5'-ATTTGAACATTATTCAAGT-3') in the promoter region of the fcs operon. The functionality of this predicted FcsR regulatory site was further confirmed by promoter-truncation experiments, where deletion of half of the FscR regulatory site or full deletion led to the abolition of expression of the fcs operon. PMID- 26159072 TI - Synthesis and Physicochemical Characterization of D-Tagatose-1-Phosphate: The Substrate of the Tagatose-1-Phosphate Kinase in the Phosphotransferase System Mediated D-Tagatose Catabolic Pathway of Bacillus licheniformis. AB - We report the first enzymatic synthesis of D-tagatose-1-phosphate (Tag-1P) by the multicomponent phosphoenolpyruvate:sugar phosphotransferase system (PEP-PTS) present in tagatose-grown cells of Klebsiella pneumoniae. Physicochemical characterization by (31)P and (1)H nuclear magnetic resonance spectroscopy reveals that, in solution, this derivative is primarily in the pyranose form. Tag 1P was used to characterize the putative tagatose-1-phosphate kinase (TagK) of the Bacillus licheniformis PTS-mediated D-tagatose catabolic pathway (Bli-TagP). For this purpose, a soluble protein fusion was obtained with the 6 His-tagged trigger factor (TF(His6)) of Escherichia coli. The active fusion enzyme was named TagK-TF(His6). Tag-1P and D-fructose-1-phosphate are substrates for the TagK TF(His6) enzyme, whereas the isomeric derivatives D-tagatose-6-phosphate and D fructose-6-phosphate are inhibitors. Studies of catalytic efficiency (kcat/Km) reveal that the enzyme specificity is markedly in favor of Tag-1P as the substrate. Importantly, we show in vivo that the transfer of the phosphate moiety from PEP to the B. licheniformis tagatose-specific Enzyme II in E. coli is inefficient. The capability of the PTS general cytoplasmic components of B. subtilis, HPr and Enzyme I to restore the phosphate transfer is demonstrated. PMID- 26159074 TI - The Phosphotransferase System in Solventogenic Clostridia. AB - The acetone-butanol-ethanol fermentation employing solventogenic clostridia was a major industrial process during the 20th century, but declined for economic reasons. In recent times, interest in the process has been revived due to the perceived potential of butanol as a superior biofuel. Redevelopment of an efficient fermentation process will require a detailed understanding of the physiology of carbohydrate utilization by the bacteria. Genome sequences have revealed that, as in other anaerobes, the phosphotransferase system (PTS) and associated regulatory functions are likely to play an important role in sugar uptake and its regulation. The genomes of Clostridium acetobutylicum and C. beijerinckii encode 13 and 43 phosphotransferases, respectively. Characterization of clostridial phosphotransferases has demonstrated that they are involved in the uptake and phosphorylation of hexoses, hexose derivatives and disaccharides, although the functions of many systems remain to be determined. Glucose is a dominant sugar which represses the utilization of other carbon sources, including the non-PTS pentose sugars xylose and arabinose, by the clostridia. Targeting of the CcpA-dependent mechanism of carbon catabolite repression has been shown to be an effective strategy for reducing the repressive effects of glucose, indicating potential for developing strains with improved fermentation performance. PMID- 26159075 TI - A Search for Ribonucleic Antiterminator Sites in Bacterial Genomes: Not Only Antitermination? AB - BglG/LicT-like proteins are transcriptional antiterminators that prevent termination of transcription at intrinsic terminators by binding to ribonucleic antiterminator (RAT) sites and stabilizing an RNA conformation which is mutually exclusive with the terminator structure. The known RAT sites, which are located in intergenic regions of sugar utilization operons, show low sequence conservation but significant structural analogy. To assess the prevalence of RATs in bacterial genomes, we employed bioinformatic tools that describe RNA motifs based on both sequence and structural constraints. Using descriptors with different stringency, we searched the genomes of Escherichiacoli K12, uropathogenic E. coli and Bacillus subtilis for putative RATs. Our search identified all known RATs and additional putative RAT elements. Surprisingly, most putative RATs do not overlap an intrinsic terminator and many reside within open reading frames (ORFs). The ability of one of the putative RATs, which is located within an antiterminator-encoding ORF and does not overlap a terminator, to bind to its cognate antiterminator protein in vitro and in vivo was confirmed experimentally. Our results suggest that the capacity of RAT elements has been exploited during evolution to mediate activities other than antitermination, for example control of transcription elongation or of RNA stability. PMID- 26159076 TI - Regulation of the Utilization of Amino Sugars by Escherichia coli and Bacillus subtilis: Same Genes, Different Control. AB - Amino sugars are dual-purpose compounds in bacteria: they are essential components of the outer wall peptidoglycan (PG) and the outer membrane of Gram negative bacteria and, in addition, when supplied exogenously their catabolism contributes valuable supplies of energy, carbon and nitrogen to the cell. The enzymes for both the synthesis and degradation of glucosamine (GlcN) and N acetylglucosamine (GlcNAc) are highly conserved but during evolution have become subject to different regulatory regimes. Escherichia coli grows more rapidly using GlcNAc as a carbon source than with GlcN. On the other hand, Bacillus subtilis, but not other Bacilli tested, grows more efficiently on GlcN than GlcNAc. The more rapid growth on this sugar is associated with the presence of a second, GlcN-specific operon, which is unique to this species. A single locus is associated with the genes for catabolism of GlcNAc and GlcN in E. coli, although they enter the cell via different transporters. In E. coli the amino sugar transport and catabolic genes have also been requisitioned as part of the PG recycling process. Although PG recycling likely occurs in B. subtilis, it appears to have different characteristics. PMID- 26159077 TI - Cross-Talk between the Canonical and the Nitrogen-Related Phosphotransferase Systems Modulates Synthesis of the KdpFABC Potassium Transporter in Escherichia coli. AB - Many Proteobacteria possess the regulatory nitrogen-related phosphotransferase system (PTS(Ntr)), which operates in parallel to the transport PTS. PTS(Ntr) is composed of the proteins EI(Ntr) and NPr and the final phosphate acceptor EIIA(Ntr). Both PTSs can exchange phosphoryl groups among each other. Proteins governing K(+) uptake represent a major target of PTS(Ntr) in Escherichia coli. Nonphosphorylated EIIA(Ntr) binds and stimulates the K(+) sensor KdpD, which activates expression of the kdpFABC operon encoding a K(+) transporter. Here we show that this regulation also operates in an ilvG(+) strain ruling out previous concern about interference with a nonfunctional ilvG allele present in many strains. Furthermore, we analyzed phosphorylation of EIIA(Ntr). In wild-type cells EIIA(Ntr) is predominantly phosphorylated, regardless of the growth stage and the utilized carbon source. However, cross-phosphorylation of EIIA(Ntr) by the transport PTS becomes apparent in the absence of EI(Ntr): EIIA(Ntr) is predominantly nonphosphorylated when cells grow on a PTS sugar and phosphorylated when a non-PTS carbohydrate is utilized. These differences in phosphorylation are transduced into corresponding kdpFABC transcription levels. Thus, the transport PTS may affect phosphorylation of EIIA(Ntr) and accordingly modulate processes controlled by EIIA(Ntr). Our data suggest that this cross-talk becomes most relevant under conditions that would inhibit activity of EI(Ntr). PMID- 26159078 TI - Modeling the Interplay of Pseudomonas putida EIIA with the Potassium Transporter KdpFABC. AB - The nitrogen phosphotransferase system (PTS(Ntr)) of Pseudomonas putida is a key regulatory device that participates in controlling many physiological processes in a posttranscriptional fashion. One of the target functions of the PTS(Ntr) is the regulation of potassium transport. This is mediated by the direct interaction of one of its components with the sensor kinase KdpD of the two-component system controlling transcription of the kdpFABC genes. From a detailed experimental analysis of the activity of the kdpF promoter in P. putida wild-type and pts mutant strains with varying potassium concentrations, we had highly time-resolved data at hand, describing the influence of the PTS(Ntr) on the transcription of the KdpFABC potassium transporter. Here, this data was used to construct a mathematical model based on a black box approach. The model was able to describe the data quantitatively with convincing accuracy. The qualitative interpretation of the model allowed the prediction of two general points describing the interplay between the PTS(Ntr) and the KdpFABC potassium transporter: (1) the influence of cell number on the performance of the kdpF promoter is mainly by dilution by growth and (2) potassium uptake is regulated not only by the activity of the KdpD/KdpE two-component system (in turn influenced by PtsN). An additional controller with integrative behavior is predicted by the model structure. This suggests the presence of a novel physiological mechanism during regulation of potassium uptake with the KdpFABC transporter and may serve as a starting point for further investigations. PMID- 26159079 TI - Inactivation of the PTS as a Strategy to Engineer the Production of Aromatic Metabolites in Escherichia coli. AB - Laboratory and industrial cultures of Escherichia coli employ media containing glucose which is mainly transported and phosphorylated by the phosphotransferase system (PTS). In these strains, 50% of the phosphoenolpyruvate (PEP), which results from the catabolism of transported glucose, is used as a phosphate donor for its phosphorylation and translocation by the PTS. This characteristic of the PTS limits the production of industrial biocommodities that have PEP as a precursor. Furthermore, when E. coli is exposed to carbohydrate mixtures, the PTS prevents expression of catabolic and non-PTS transport genes by carbon catabolite repression and inducer exclusion. In this contribution, we discuss the main strategies developed to overcome these potentially limiting effects in production strains. These strategies include adaptive laboratory evolution selection of PTS( ) Glc(+) mutants, followed by the generation of strains that recover their ability to grow with glucose as a carbon source while allowing the simultaneous consumption of more than one carbon source. We discuss the benefits of using alternative glucose transport systems and describe the application of these strategies to E. coli strains with specific genetic modifications in target pathways. These efforts have resulted in significant improvements in the production of diverse biocommodities, including aromatic metabolites, biofuels and organic acids. PMID- 26159080 TI - Biofilm Growth of Escherichia coli Is Subject to cAMP-Dependent and cAMP Independent Inhibition. AB - We established that Escherichia coli strain 15 (ATCC 9723) produces both curli and cellulose, and forms robust biofilms. Since this strain is wild type with respect to the phosphoenolpyruvate:sugar phosphotransferase system (PTS), it is an ideal strain in which to investigate the effects of the PTS on the biofilm growth of E. coli. We began by looking into the effects of PTS and non-PTS sugars on the biofilm growth of this strain. All the sugars tested tended to activate biofilm growth at low concentrations but to inhibit biofilm growth at high concentrations. Acidification of the medium was an inhibitory factor in the absence of buffer, but buffering to prevent a pH drop did not prevent the inhibitory effects of the sugars. The concentration at which inhibition set in varied from sugar to sugar. For most sugars, cyclic (c)AMP counteracted the inhibition at the lowest inhibitory concentrations but became ineffective at higher concentrations. Our results suggest that cAMP-dependent catabolite repression, which is mediated by the PTS in E. coli, plays a role in the regulation of biofilm growth in response to sugars. cAMP-independent processes, possibly including Cra, also appear to be involved, in addition to pH effects. PMID- 26159081 TI - Control of Transposon-Mediated Directed Mutation by the Escherichia coli Phosphoenolpyruvate:Sugar Phosphotransferase System. AB - The phosphoenolpyruvate:sugar phosphotransferase system (PTS) has been shown to control transport, cell metabolism and gene expression. We here present results supporting the novel suggestion that in certain instances it also regulates the mutation rate. Directed mutations are defined as mutations that occur at higher frequencies when beneficial than when neutral or detrimental. To date, the occurrence of directed point mutations has not been documented and confirmed, but a few examples of transposon-mediated directed mutations have been reported. Here we focus on the first and best-studied example of directed mutation, which involves the regulation of insertion sequence-5 hopping into a specific site upstream of the glpFK glycerol utilization operon in Escherichia coli. This insertional event specifically activates expression of the glpFK operon, allowing the growth of wild-type cells with glycerol as a carbon source in the presence of nonmetabolizable glucose analogues which normally block glycerol utilization. The sugar-transporting PTS controls this process by regulating levels of cytoplasmic glycerol-3-phosphate and cyclic (c)AMP as established in previous publications. Direct involvement of the glycerol repressor, GlpR, and the cAMP receptor protein, Crp, in the regulation of transposon-mediated directed mutation has been demonstrated. PMID- 26159083 TI - Chronic administration of ghrelin regulates plasma glucose and normalizes insulin levels following fasting hyperglycemia and hyperinsulinemia. AB - Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor. The majority of the previous studies have shown that the short-term ghrelin treatment induces hyperglycemia and hypoinsulinemia in healthy humans and rodents. However, the results obtained from long-term treatment with ghrelin are not clear enough. In this study, we assessed acute (1 day) and chronic (21 days) effects of intraperitoneally administered ghrelin (at different doses of 1, 10 and 20 MUg/kg) during a 12-h fasting period in rats using glucose oxidase method and direct sandwich ELISA (the Enzyme-Linked Immunosorbent Assay) and then compared the effects of exogenous ghrelin on blood glucose and insulin levels on day 21 with those on day 1. The results showed that acute ghrelin administration markedly increased fasting plasma glucose at doses of 1 and 10 MUg/kg as well as insulin levels at 1 MUg/kg in comparison to control values. Ghrelin (at 1 MUg/kg) altered plasma glucose but not insulin levels on the 21st day compared to control values. In addition, the comparison of the influence of ghrelin administration on plasma glucose and insulin levels on day 21 with those on the first day revealed that the chronic administration of ghrelin notably decreased plasma glucose and insulin levels relative to the acute ghrelin treatment. These findings indicate that hyperglycemia and hyperinsulinemia caused by the exogenous ghrelin during acute treatment are temporary and prolonged treatment with ghrelin regulates plasma glucose and restores insulin to normal levels, suggesting a possible role for ghrelin in improving insulin resistance. PMID- 26159084 TI - What do you mean, 'resilient'? AB - In a world beset by environmental disasters and anthropogenic disturbances, resilience might be the key to the persistence of natural systems. Yet, the 'measurement' of resilience is hampered by the multiple (and often conflicting) processes that yield the response of systems to insult. We recommend the simultaneous consideration of 'resistance' and 'recovery' as measurable components that together represent resilience. PMID- 26159085 TI - Dosimetric distribution to the teeth of patients with head and neck cancer who underwent radiotherapy. PMID- 26159086 TI - Slow-growing mass and expansive swelling in the maxilla. PMID- 26159087 TI - A woman with rare blastic plasmacytoid dendritic cell neoplasm on the face. AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a recently classified cutaneous lymphoma derived from the precursor of plasmacytoid dendritic cells with extremely poor prognosis. It has atypical morphologic features and is rarely found on the face. We report here a case of a 37-year-old woman with the rare BPDCN involving the maxillofacial region. She had a 2-month history of violaceous and traumatic hematoma-like skin lesions located on the left side of the face. Pathologic diagnosis of BPDCN was established by a skin biopsy, and the patient died 2 months later. Thus, a strong suspicion and early detection of BPDCN are essential in the case of violaceous or traumatic hematoma-like skin lesions, especially on the face. PMID- 26159088 TI - Protective effect of berberine, an isoquinoline alkaloid ameliorates ethanol induced oxidative stress and memory dysfunction in rats. AB - Memory impairment induced by ethanol in rats is a consequence of changes in the CNS that are secondary to impaired oxidative stress and cholinergic dysfunction. Treatment with antioxidants and cholinergic agonists are reported to produce beneficial effects in this model. Berberine, an isoquinoline alkaloid is reported to exhibit antioxidant effect and cholinesterase (ChE) inhibitor activity. However, no report is available on the influence of berberine on ethanol-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in ethanol-induced rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameter of oxidative stress and cholinesterase (ChE) activity as a marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Forty five days after ethanol treated rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., once a day for 45days) improved cognitive performance, and lowered oxidative stress and ChE activity in ethanol treated rats. In another set of experiments, berberine (100mg/kg) treatment during training trials also improved learning and memory, and lowered oxidative stress and ChE activity. Chronic treatment (45days) with vitamin C, and donepezil during training trials also improved ethanol-induced memory impairment and reduced oxidative stress and/or cholinesterase activity. In conclusion, the present study demonstrates that treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in ethanol treated rats. PMID- 26159090 TI - Differences between follicular waves 1 and 2 in patterns of emergence of 2-mm follicles, associated FSH surges, and ovarian vascular perfusion in heifers. AB - The emergence (first detection) of 2-mm follicles, FSH surges, and ovarian vascular perfusion for follicular wave 1 and surge 1 (n = 26) and wave 2 and surge 2 (n = 25) were studied daily in heifers. The day the future dominant follicle was closest to 5.5 mm was designated Day 0 for each wave. In wave 1, many 2-mm follicles (41%) emerged on Days -5 to -3, whereas FSH surge 1 did not begin until Day -3. Concentration of FSH increased abruptly in 1 day to a peak on the day of maximal number of emerging 2-mm follicles, although the day of maximal number relative to Day 0 differed among individuals. The first emergence of 2-mm follicles in wave 2 occurred concurrently with the first increase in the FSH of surge 2. In wave 1, ovarian resistance to vascular perfusion was negatively correlated (r = -0.48, P < 0.05) with a number of 2-mm follicles on Days -4 to -1 for ovaries that did not contain the preovulatory follicle; vascular perfusion increased with an increase in the number of small follicles. The following hypotheses were supported for wave 1 but not for wave 2: (1) an increase in the number of emerging 2-mm follicles of a follicular wave occurs before the beginning of an increase in FSH, (2) the day of maximal number of emerging 2-mm follicles occurs concurrently with an abrupt FSH increase on different days among individuals, and (3) the association between the number of emerging 2-mm follicles and the extent of ovarian vascular perfusion is positive. PMID- 26159089 TI - Animal models of social contact and drug self-administration. AB - Social learning theories of drug abuse propose that individuals imitate drug use behaviors modeled by social peers, and that these behaviors are selectively reinforced and/or punished depending on group norms. Historically, animal models of social influence have focused on distal factors (i.e., those factors outside the drug-taking context) in drug self-administration studies. Recently, several investigators have developed novel models, or significantly modified existing models, to examine the role of proximal factors (i.e., those factors that are immediately present at the time of drug taking) on measures of drug self administration. Studies using these newer models have revealed several important conclusions regarding the effects of social learning on drug abuse: 1) the presence of a social partner influences drug self-administration, 2) the behavior of a social partner determines whether social contact will increase or decrease drug intake, and 3) social partners can model and imitate specific patterns of drug self-administration. These findings are congruent with those obtained in the human laboratory, providing support for the cross-species generality and validity of these preclinical models. This mini-review describes in detail some of the preclinical animal models used to study social contact and drug self administration to guide future research on social learning and drug abuse. PMID- 26159091 TI - Ectopic liver and gallbladder in a cloned dog: Possible nonheritable anomaly. AB - Ectopic liver and gallbladder are rare anomalies usually not accompanied by any symptoms and are found during surgical exploration or autopsy. We aimed to find a cause of this anomaly using somatic cell nuclear transfer (SCNT) technology, which can produce genetically identical organisms. A cloned beagle having ectopic organs was produced and died on the day of birth. Major and ectopic organs were fixed and underwent histologic analysis. SCNT was performed using cells derived from the dead puppy to produce reclones. Normality of internal organs in the original donor dog and recloned dogs was evaluated by computed tomography. While a liver without the gallbladder was located in the abdominal cavity of the cloned dog, a well-defined, reddish brown mass with a small sac was also positioned outside of the thoracic cavity. Histologically, they presented as normal liver and gallbladder. Five reclones were produced, and computed tomography results revealed that the original donor dog and reclones had normal liver and gallbladder structure and location. This is the first report of both ectopic liver and gallbladder in an organism and investigation on the etiology of these abnormalities. Normal organ structure and position in the original donor dog and reclones suggests that the ectopic liver and gallbladder is a possible nonheritable anomaly. PMID- 26159092 TI - Effect of different media additives on capacitation of frozen-thawed ram spermatozoa as a potential replacement for estrous sheep serum. AB - Capacitation is a key process through which spermatozoa acquire their fertilizing ability. This event is required for the successful application of assisted reproductive technologies such as IVF. The aim of the present study was to investigate the effect of using a synthetic oviductal fluid medium supplemented with either heparin-hypotaurine alone, in combination with progesterone (P4), 17beta-estradiol (E2), or BSA, or just beta-cyclodextrin, in replacement for estrous sheep serum (ESS) for ram sperm capacitation. After incubation in the corresponding media for 15 (time 0) or 60 minutes, sperm function was evaluated by computerized sperm motility analysis and flow cytometry (plasma membrane status and fluidity). Treatments rendering the best results in regards to sperm function parameters related to capacitation were used for an IVF test. Herein, neither heparin-hypotaurine (alone), or in combination with P4, or E2, nor beta cyclodextrin induced capacitation-related changes in frozen-thawed ram spermatozoa. Only the medium supplemented with heparin-hypotaurine-BSA was able to induce changes compatible with in vitro capacitation relating to sperm motility pattern and plasma membrane fluidity, comparable to those in ESS containing medium. Both media yielded sperm parameter values that differed (P < 0.05) from those obtained in the rest of the media tested. However, after the IVF trial, BSA was unable to support cleavage rates (21.80%) comparable to those obtained with ESS (52.60%; P < 0.05). We conclude that heparin-hypotaurine, P4, E2, beta-cyclodextrin, or BSA is not suitable for replacing ESS in capacitation and fertilization media for ram spermatozoa. PMID- 26159093 TI - Good governance competencies in public health to train public health physicians. AB - OBJECTIVES: This study aimed at assessing public health residents' perceived health system governance (HSG) training needs and to define a competency framework for "good governance" to improve Public Health physicians' curricula. METHODS: A questionnaire was administered to all Italian medical residents on postgraduate courses in Hygiene and Preventive medicine. Twenty-five (78.1%) of the 32 Italian Schools of Public Health and 299/535 residents (55.9%) took part in this survey. The public health governance competency framework was developed from roles and responsibility at different levels of governance in the Italian Health System context. RESULTS: The questionnaire revealed that residents felt the need for more training on all the proposed HSG-related topics. Different governance functions, strategic planning, operational planning, and operational programming were considered when defining roles and responsibilities. CONCLUSIONS: More efforts should be made to provide organic training plans tailored to the needs of local and national health system. The competencies framework for good governance could be useful for planning professional training in both the academic and the health system settings. PMID- 26159094 TI - Evaluation the effect of thiamin deficiency on intestinal immunity of young grass carp (Ctenopharyngodon idella). AB - Our study explored the effect of dietary thiamin on growth and immunity (intestine, head kidney, spleen and liver) of young grass carp (Ctenopharyngodon idella). Fish were fed diets containing six graded levels of thiamin at 0.12-2.04 mg/kg diet for 8 weeks. The percentage weight gain (PWG), feed intake and feed efficiency were lower in fish fed the 0.12 mg/kg diet. Thiamin deficiency decreased complement 3 content, lysozyme (LA) and acid phosphatase activities, mRNA levels of hepcidin and interleukin (IL) 10, elevated mRNA levels of interferon gamma2, tumor necrosis factor alpha, IL-1beta and IL-8 in intestine, head kidney, spleen and liver. The mRNA levels of inhibitor protein-kappaBalpha, target of rapamycin (TOR) and NF-E2-related factor 2 (Nrf2), the activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase were down-regulated, mRNA levels of myosin light-chain kinase (MLCK), IkappaB kinases (IKKbeta and IKKgamma), nuclear factor kappaB P65 (NF-kappaB P65) and Kelch-like-ECH-associated protein 1a (Keap1a) were up-regulated in the intestine of fish fed the thiamin-deficient diet. Additionally, thiamin deficiency decreased claudin b, c and 3, ZO-1 and occludin mRNA levels in each intestinal segment, increased claudin 12 and claudin 15a mRNA levels in distal intestine. In conclusion, thiamin deficiency decreased fish growth and immunity of intestine, head kidney, spleen and liver. The dietary thiamin requirement of young grass carp (242-742 g) based on intestinal LA activity or PWG were determined to be 1.15 or 0.90 mg/kg diet, respectively. PMID- 26159095 TI - Identification of five anti-lipopolysaccharide factors in oriental river prawn, Macrobrachium nipponense. AB - Anti-lipopolysaccharide factors (ALFs) are a group of antimicrobial peptides (AMPs) with broad-spectrum antimicrobial activities and antiviral activities mainly found in crustaceans and horseshoe crabs. In the present study, we identified 5 ALF expression sequence tags (ESTs) through analysis of the established M. nipponense transcriptome, and cloned their full-length cDNA sequences using rapid amplification of cDNA ends (RACE) method. The 5 ALFs were designated as MnALF1-5, and all of them showed high similarity with their Macrobrachium rosenbergii homologs in the phylogenetic analyses, especially in LPS binding domains. In healthy adult prawns, we found the highest expression of MnALF2 and MnALF4 in haemocytes, and the highest expression of MnALF4 and MnALF3 in intestine. Some isoforms of MnALF were down-regulated but the majority was up regulated in different prawn tissues upon Aeromonas hydrophila challenge. To conform the expected antimicrobial activities harbored in MnALFs' LPS binding domains, we used a synthesized peptide cMnALF24 that corresponds to the LPS binding domain of MnALF2 as a representative molecule for the antibacterial activity test, and found that cMnALF24 possessed strong and broad-spectrum antibacterial activity against Gram positive and Gram negative bacteria, but no inhibition activity against fungi; Meanwhile, in the hemolytic test, cMnALF24 showed weak hemolysis activities (around 10%) to the rabbit red blood cells at concentrations of 0.67-33.50 MUM. This study provides insights into understanding the antibacterial function of ALFs in the innate immunity of freshwater prawn, and reports a peptide that can be a potential drug candidate with good efficacy against bacterial infection and low toxicity to host cells. PMID- 26159096 TI - Placento-Cranial Adhesions in Amniotic Band Syndrome and the Role of Surgery in Their Management: An Unusual Case Presentation and Systematic Literature Review. AB - Amniotic band syndrome is a group of sporadic congenital anomalies that involve the limbs, craniofacial regions and trunk, ranging from simple digital band constriction to complex craniofacial and central nervous system abnormalities. Placento-cranial adhesions in amniotic band syndrome are extremely rare, and severe conditions are associated with high morbidity and mortality rates. In this study, we pooled placento-cranial adhesion case reports that were published in the medical literature and added an unpublished case from our institution. The purpose of this article was to review and discuss the clinical features and outcomes of placento-cranial adhesions in amniotic band syndrome. PMID- 26159097 TI - A Maximum Radius for Habitable Planets. AB - We compute the maximum radius a planet can have in order to fulfill two constraints that are likely necessary conditions for habitability: 1- surface temperature and pressure compatible with the existence of liquid water, and 2- no ice layer at the bottom of a putative global ocean, that would prevent the operation of the geologic carbon cycle to operate. We demonstrate that, above a given radius, these two constraints cannot be met: in the Super-Earth mass range (1-12 Mearth), the overall maximum that a planet can have varies between 1.8 and 2.3 Rearth. This radius is reduced when considering planets with higher Fe/Si ratios, and taking into account irradiation effects on the structure of the gas envelope. PMID- 26159098 TI - Decrease in levels of the evolutionarily conserved microRNA miR-124 affects oligodendrocyte numbers in Zebrafish, Danio rerio. AB - Oligodendrocytes produce multi-lamellar myelin membranes that surround axons in the central nervous system (CNS). Preservation and generation of myelin are potential therapeutic targets for dysmyelinating and demyelinating diseases. MicroRNAs (miRNAs) play a vital role in oligodendrocyte differentiation and overall CNS development. miR-124 is a well-conserved neuronal miRNA with important roles in neuronal differentiation and function. miR-124 levels increase following loss of myelin in both human and rodent brains. While the role of neuronal miR-124 in neurogenesis has been established, its effects on axonal outgrowth and oligodendrocytes are not currently known. We therefore explored the possible effect of selective knockdown of miR-124 in Danio rerio using a morpholino-based knockdown approach. No morphological abnormalities or loss of motor neurons were detected despite loss of axonal outgrowth. Morpholino-based knockdown of miR-124 led to reciprocal increases in mRNA levels of target genes that inhibit axonal and dendritic projections. Importantly, loss of miR-124 led to decreased oligodendrocyte cell numbers and myelination of axonal projections in the ventral hindbrain. Taken together, our results add a new dimension to the existing complexity of neuron-glial relationships and highlight the utility of Danio rerio as a model system to investigate such interactions. PMID- 26159099 TI - Droplet-based microfluidic platform for measurement of rapid erythrocyte water transport. AB - Cell membrane water permeability is an important determinant of epithelial fluid secretion, tissue swelling, angiogenesis, tumor spread and other biological processes. Cellular water channels, aquaporins, are important drug targets. Water permeability is generally measured from the kinetics of cell volume change in response to an osmotic gradient. Here, we developed a microfluidic platform in which cells expressing a cytoplasmic, volume-sensing fluorescent dye are rapidly subjected to an osmotic gradient by solution mixing inside a ~0.1 nL droplet surrounded by oil. The solution mixing time was <10 ms. Osmotic water permeability was deduced from a single, time-integrated fluorescence image of an observation area in which the time after mixing was determined through spatial position. Water permeability was accurately measured in aquaporin-expressing erythrocytes with half-times for osmotic equilibration down to <50 ms. Compared with conventional water permeability measurements using costly stopped-flow instrumentation, the microfluidic platform here utilizes sub-microliter blood sample volume, does not suffer from mixing artifacts, and replaces challenging kinetic measurements by single image capture using a standard laboratory fluorescence microscope. PMID- 26159100 TI - Resting-state functional connectivity of dentate nucleus is associated with tremor in Parkinson's disease. AB - Cerebello-thalamo-cortical circuit has been indicated important for tremor in Parkinson's disease (PD), but the role of dentate nucleus (DN) in parkinsonian tremor remains unclear. To investigate whether DN plays a role in PD tremor, we recruited 50 PD and 29 age-matched health controls (HC). The patients were divided into tremor-dominant (TD) and non-tremor-dominant (NTD) groups. We collected resting-state fMRIs data for each subject. The bilateral DN was then chosen as the region of interest to examine PD tremor-related network changes, as well as its correlation with tremor severity. Voxel-wise functional connectivity analysis revealed that the bilateral DN had higher connectivity with the bilateral cerebellar anterior lobe, and had lower connectivity with the bilateral prefrontal cortex in TD compared to the HC and NTD groups. Functional connectivity of the bilateral DN with the bilateral cerebellar posterior lobe was also higher in TD than NTD group. Functional connectivity between the bilateral DN and the bilateral cerebellar posterior lobe showed positive correlation with tremor severity, while that between the bilateral DN and the bilateral prefrontal cortex displayed negative correlation. Our study demonstrates higher dentato cerebellar connectivity and lower dentato-prefrontal connectivity in TD patients, which might be involved in the pathogenesis of PD tremor. And we conclude that DN might be associated with the pathogenesis of PD tremor. PMID- 26159101 TI - CSF pressure, papilledema grade, and response to acetazolamide in the Idiopathic Intracranial Hypertension Treatment Trial. AB - Previous reports suggest an association between the degree of optic nerve head edema and CSF pressure (CSFp) in idiopathic intracranial hypertension (IIH). We hypothesized that CSFp would be associated with Frisen papilledema grade (FPG) and other clinical features, and that FPG would modify the CSFp response to acetazolamide in participants in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). In the IIHTT, eligible patients underwent lumbar puncture (LP) prior to enrollment and were randomly assigned to one of two treatment groups: acetazolamide plus supervised diet or placebo plus supervised diet. Trial eligibility required baseline CSFp >=250 mm H2O or >=200 mm H2O with compelling clinical or imaging IIH findings. Associations between CSFp and FPG and other clinical features were examined at baseline. The effect of acetazolamide on 6-month change in CSFp was examined in those with low FPG (grades I-III) and those with high FPG (grades IV-V) at baseline. All 165 enrolled subjects had a baseline LP and 85 had an LP at 6 months. There was an association between CSFp and FPG at baseline: CSFp was more elevated in subjects with high FPG (378 +/- 90 mm H2O, n = 50) than in subjects with low FPG (331 +/- 77, n = 115, p = 0.002). At 6 months, acetazolamide had a similar effect on CSFp in subjects with high FPG (-79.9 mm H2O) and in subjects with low FPG (-50.9 mm H2O, p = 0.50). We found a modest association between CSFp and FPG. Acetazolamide had a beneficial effect on CSFp regardless of baseline FPG. PMID- 26159102 TI - Deep brain stimulation and cognitive decline in Parkinson's disease: The predictive value of electroencephalography. AB - Some Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) develop new-onset cognitive decline. We examined whether clinical EEG recordings can be used to predict cognitive deterioration in PD patients undergoing STN-DBS. In this retrospective study, we used the Grand Total EEG (GTE)-score (short and total) to evaluate pre- and postoperative EEGs. In PD patients undergoing STN-DBS (N = 30), cognitive functioning was measured using Mini-Mental State Test and DemTect before and after surgery. Severity of motor impairment was assessed using the Unified Parkinson's Disease Rating Scale III. Patients were classified into patients with or without cognitive decline after STN-DBS surgery. Epidemiological data, pre- and postoperative EEG recordings as well as neuropsychological and neurological data, electrode positions and the third ventricle width were compared. A logistic regression model was used to identify predictors of cognitive decline. Motor deficits significantly improved from pre- to post-surgery, while the mean GTE-scores increased significantly. Six patients developed cognitive deterioration 4-12 months postoperatively. These patients had significantly higher preoperative GTE scores than patients without cognitive deterioration, although preoperative cognitive functioning was comparable. Electrode positions, brain atrophy and neurological data did not differ between groups. Logistic regression analysis identified the GTE-score as a significant predictor of postoperative cognitive deterioration. Data suggest that the preoperative GTE-score can be used to identify PD patients that are at high risk for developing cognitive deterioration after STN-DBS surgery even though their preoperative cognitive state was normal. PMID- 26159103 TI - Structural hallmarks of amyotrophic lateral sclerosis progression revealed by probabilistic fiber tractography. AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive limb and/or bulbar muscular weakness and atrophy. Although ALS related alterations of motor and extra-motor neuronal networks have repeatedly been reported, their temporal dynamics during disease progression are not well understood. Recently, we reported a decline of motor system activity and a concurrent increase of hippocampal novelty-evoked modulations across 3 months of ALS progression. To address whether these functional changes are associated with structural ones, the current study employed probabilistic fiber tractography on diffusion tensor imaging (DTI) data using a longitudinal design. Therein, motor network integrity was assessed by DTI-based tracking of the intracranial corticospinal tract, while connectivity estimates of occipito-temporal tracts (between visual and entorhinal, perirhinal or parahippocampal cortices) served to assess structural changes that could be related to the increased novelty-evoked hippocampal activity across time described previously. Complementing these previous functional observations, the current data revealed an ALS-related decrease in corticospinal tract structural connectivity compared to controls, while in contrast, visuo-perirhinal connectivity was relatively increased in the patient group. Importantly, beyond these between-group differences, a rise in the patients' occipito-temporal tract strengths occurred across a 3-month interval, while at the same time no changes in corticospinal tract connectivity were observed. In line with previously identified functional alterations, the dynamics of these structural changes suggest that the affection of motor- and memory related networks in ALS emerges at distinct disease stages: while motor network degeneration starts primarily during early (supposedly pre-symptomatic) phases, the hippocampal/medial temporal lobe dysfunctions arise at later stages of the disease. PMID- 26159105 TI - The effect of Young's modulus on the neuronal differentiation of mouse embryonic stem cells. AB - There is substantial evidence that cells produce a diverse response to changes in ECM stiffness depending on their identity. Our aim was to understand how stiffness impacts neuronal differentiation of embryonic stem cells (ESC's), and how this varies at three specific stages of the differentiation process. In this investigation, three effects of stiffness on cells were considered; attachment, expansion and phenotypic changes during differentiation. Stiffness was varied from 2 kPa to 18 kPa to finally 35 kPa. Attachment was found to decrease with increasing stiffness for both ESC's (with a 95% decrease on 35 kPa compared to 2 kPa) and neural precursors (with a 83% decrease on 35 kPa). The attachment of immature neurons was unaffected by stiffness. Expansion was independent of stiffness for all cell types, implying that the proliferation of cells during this differentiation process was independent of Young's modulus. Stiffness had no effect upon phenotypic changes during differentiation for mESC's and neural precursors. 2 kPa increased the proportion of cells that differentiated from immature into mature neurons. Taken together our findings imply that the impact of Young's modulus on attachment diminishes as neuronal cells become more mature. Conversely, the impact of Young's modulus on changes in phenotype increased as cells became more mature. PMID- 26159104 TI - Acidic sweep gas with carbonic anhydrase coated hollow fiber membranes synergistically accelerates CO2 removal from blood. AB - The use of extracorporeal carbon dioxide removal (ECCO2R) is well established as a therapy for patients suffering from acute respiratory failure. Development of next generation low blood flow (<500 mL/min) ECCO2R devices necessitates more efficient gas exchange devices. Since over 90% of blood CO2 is transported as bicarbonate (HCO3(-)), we previously reported development of a carbonic anhydrase (CA) immobilized bioactive hollow fiber membrane (HFM) which significantly accelerates CO2 removal from blood in model gas exchange devices by converting bicarbonate to CO2 directly at the HFM surface. This present study tested the hypothesis that dilute sulfur dioxide (SO2) in oxygen sweep gas could further increase CO2 removal by creating an acidic microenvironment within the diffusional boundary layer adjacent to the HFM surface, facilitating dehydration of bicarbonate to CO2. CA was covalently immobilized onto poly (methyl pentene) (PMP) HFMs through glutaraldehyde activated chitosan spacers, potted in model gas exchange devices (0.0151 m(2)) and tested for CO2 removal rate with oxygen (O2) sweep gas and a 2.2% SO2 in oxygen sweep gas mixture. Using pure O2 sweep gas, CA PMP increased CO2 removal by 31% (258 mL/min/m(2)) compared to PMP (197 mL/min/m(2)) (P<0.05). Using 2.2% SO2 acidic sweep gas increased PMP CO2 removal by 17% (230 mL/min/m(2)) compared to pure oxygen sweep gas control (P<0.05); device outlet blood pH was 7.38 units. When employing both CA-PMP and 2.2% SO2 sweep gas, CO2 removal increased by 109% (411 mL/min/m(2)) (P<0.05); device outlet blood pH was 7.35 units. Dilute acidic sweep gas increases CO2 removal, and when used in combination with bioactive CA-HFMs has a synergistic effect to more than double CO2 removal while maintaining physiologic pH. Through these technologies the next generation of intravascular and paracorporeal respiratory assist devices can remove more CO2 with smaller blood contacting surface areas. STATEMENT OF SIGNIFICANCE: A clinical need exists for more efficient respiratory assist devices which utilize low blood flow rates (<500 mL/min) to regulate blood CO2 in patients suffering from acute lung failure. Literature has demonstrated approaches to chemically increase hollow fiber membrane (HFM) CO2 removal efficiency by shifting equilibrium from bicarbonate to gaseous CO2, through either a bioactive carbonic anhydrase enzyme coating or bulk blood acidification with lactic acid. In this study we demonstrate a novel approach to local blood acidification using an acidified sweep gas in combination with a bioactive coating to more than double CO2 removal efficiency of HFM devices. To our knowledge, this is the first report assessing an acidic sweep gas to increase CO2 removal from blood using HFM devices. PMID- 26159107 TI - Effect of TNF-Alpha on Caveolin-1 Expression and Insulin Signaling During Adipocyte Differentiation and in Mature Adipocytes. AB - BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNF-alpha)-mediated chronic low grade inflammation of adipose tissue is associated with obesity and insulin resistance. Caveolin-1 (Cav-1) is the central component of adipocyte caveolae and has an essential role in the regulation of insulin signaling. The effects of TNF alpha on Cav-1 expression and insulin signaling during adipocyte differentiation and in mature adipocytes were studied. METHODS: 3T3-L1 cells were differentiated (21 days) in the presence TNF-alpha (10 ng/mL) and mature adipocytes were also treated with TNF-alpha for 48 hours. Cav-1 and insulin receptor (IR) gene methylation were determined as well as Cav-1, IR, PKB/AKT-2 and Glut-4 expression and activation by real time RT-PCR and western blot. Baseline and insulin-induced glucose uptake was measured by the 2-[C14]-deoxyglucose uptake assay. RESULTS: TNF-alpha slowed down the differentiation program, hindering the expression of some insulin signaling intermediates without fully eliminating insulin-mediated glucose uptake. In mature adipocytes, TNF-alpha did not compromise lipid-storage capacity, but downregulated the expression of the insulin signaling intermediates, totally blocking insulin-mediated glucose uptake. Insulin sensitivity correlated with the level of activated phospho-Cav-1 in both situations, strongly suggesting the direct contribution of Cav-1 to the maintenance of this physiological response. CONCLUSION: Cav-1 activation by phosphorylation seems to be essential for the maintenance of an active and insulin-sensitive glucose uptake. PMID- 26159106 TI - The structural and optical properties of type III human collagen biosynthetic corneal substitutes. AB - The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2 methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2-9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. PMID- 26159108 TI - Gender Differences and Predictors of Mortality in Takotsubo Cardiomyopathy: Analysis from the National Inpatient Sample 2009-2010 Database. AB - OBJECTIVES: Takotsubo cardiomyopathy (TC) is characterized by left-ventricle apical ballooning with elevated cardiac biomarkers and electrocardiographic changes similar to an acute coronary syndrome. We studied the prevalence, in hospital mortality, and predictors of mortality in TC. METHODS: All patients >=18 years of age diagnosed with TC were identified in the Nationwide Inpatient Sample (NIS) 2009-2010 database using the 9th revision of the International Classification of Diseases (ICD) 429.83. Demographics, conventional risk factors (diabetes, hypertension, hyperlipidemia, and tobacco abuse), acute critical illnesses like sepsis, acute cerebrovascular disease (cerebrovascular accident; CVA), acute respiratory insufficiency, and acute renal failure, and chronic conditions (anxiety, depression, and malignancy) were studied. RESULTS: The prevalence of TC was 0.02% (n = 7,510). The total in-hospital mortality rate was 2.4%, with a higher mortality in men (4.8%) than in women (2.1%). Sepsis (9 vs. 4.2%; p < 0.01) was more prevalent in men with an increased prevalence of other critical illness, although this was not statistically significant. Age (OR 1.05; 95% CI 1.01-1.09), malignancy (OR 3.38; 95% CI 1.35-8.41), acute renal failure (OR 5.4; 95% CI 2.2-13.7), acute CVA (OR 9.4; 95% CI 2.96-29.8), and acute respiratory failure (OR 11.1; 95% CI 3.9-31.1) predicted mortality in fully adjusted models. CONCLUSION: A higher mortality was seen in men, likely related to the increased prevalence of acute critical illnesses, ventricular arrhythmia, and sudden cardiac arrest. Acute CVA and respiratory failure were the strongest predictors of mortality. (c) 2015 S. Karger AG, Basel. PMID- 26159109 TI - Reported positive and negative outcomes associated with a self-practice/self reflection cognitive-behavioural therapy exercise for CBT trainees. AB - OBJECTIVE: The aim of the current study was to identify outcomes of a self practice/self-reflection (SP/SR) exercise for trainee clinical psychologists. METHOD: Thirty-two trainees enrolled in their first year of a UK university doctoral clinical psychology training programme completed an online questionnaire following an eight-week exercise. RESULTS: Findings indicated an endorsement of many previously reported benefits of exercise participation, but also the identification of negative outcomes. Thematic analysis of qualitative data revealed that outcomes could be grouped into two main thematic domains (individual task outcomes and task organization issues) along with several subordinate themes. CONCLUSION: SP/SR is a useful tool in the development of trainee CBT therapist competences. There has been limited previous recognition of potential negative outcomes from this type of exercise. However, these can provide additional impetus for therapist skill development. PMID- 26159110 TI - Elevated serum and synovial fluid levels of interleukin-37 in patients with rheumatoid arthritis: Attenuated the production of inflammatory cytokines. AB - OBJECTIVES: To measure the serum and synovial fluid (SF) levels of interleukin (IL)-37 in patients with rheumatoid arthritis (RA) and to investigate the effect of recombinant human (rh)IL-37 on inflammatory cytokine production (tumor necrosis factor [TNF]-alpha, IL-6, IL-17 and IL-10) by peripheral blood mononuclear cells (PBMCs) in RA patients. METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to analyse the serum and SF IL-37 levels. RhIL-37 was used to stimulate RA patient PBMCs. The supernatant TNF-alpha, IL-17, IL-6 and IL-10 levels were detected with ELISAs. RESULTS: The serum IL-37 levels in RA patients were significantly increased compared with those of osteoarthritis (OA) and healthy controls (HC), and they were especially elevated in RA patients with positive rheumatoid factor (RF) and anti-citrullinated peptide antibody (CCP) levels. Furthermore, the serum IL-37 levels were positively correlated with RF values. In 20 matched RA SF and serum samples, the SF IL-37 levels were much higher than those in the serum. After anti-TNF-alpha therapy, the serum IL-37 levels significantly decreased. Additionally, rhIL-37 significantly down regulated TNF-alpha, IL-17 and IL-6 production by RA patient PBMCs. CONCLUSIONS: IL-37 is an important anti-inflammatory cytokine in the control of RA pathogenesis by suppressing inflammatory cytokine production. Thus, IL-37 administration may be a novel therapy for RA. PMID- 26159111 TI - Regulation of type I-interferon responses in the human epidermal melanocyte cell line SKMEL infected by the Ross River alphavirus. AB - Melanocytes are melanin-producing cells and with emerging innate immune functions including the expression of antiviral interferon-type I cytokines. We herein ascertained the susceptibility of the human melanocytes to Ross River alphavirus (RRV) infection and analyzed the subsequent immune responses. We demonstrated for the first time that (1) SKMEL-28 melanocyte cell line was susceptible to RRV infection and displaying major cytopathic activities and (2) RRV interfered with the interferon-type I response by altering nuclear translocation of pSTAT1 and pSTAT2 in infected SKMEL-28. These results suggest that the human melanoma cell line SKMEL-28 is a valuable model to analyze the mechanisms involved in severe skin manifestations and melanocyte's immunity at the portal of entry of major infection by arboviruses. PMID- 26159113 TI - Hunting for dark matter with ultra-stable fibre as frequency delay system. AB - Many cosmological observations point towards the existence of dark-matter(DM) particles and consider them as the main component of the matter content of the universe. The goal of revealing the nature of dark-matter has triggered the development of new, extremely sensitive detectors. It has been demonstrated that the frequencies and phases of optical clock have a transient shift during the DMs' arrival due to the DM-SM(Standard Model) coupling. A simple, reliable and feasible experimental scheme is firstly proposed in this paper, based on "frequency-delay system" to search dark-matter by "self-frequency comparison" of an optical clock. During the arrival of a dark-matter, frequency discrepancy is expected between two signals with a short time difference(~ms) of the same optical clock to exhibit the interaction between atoms and dark-matter. Furthermore, this process can determine the exact position of dark-matter when it is crossing the optical clocks, therefore a network of detecting stations located in different places is recommended to reduce the misjudgment risk to an acceptable level. PMID- 26159112 TI - Low serum 25-hydroxyvitamin D is associated with increased risk of stress fracture during Royal Marine recruit training. AB - The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training. Poor vitamin D status was associated with an increased risk of stress fracture. Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status. INTRODUCTION: Stress fracture is a common overuse injury in military recruits, including Royal Marine (RM) training in the UK. RM training is recognised as one of the most arduous basic training programmes in the world. Associations have been reported between serum 25-hydroxyvitamin D (25(OH)D) and risk of stress fracture, but the threshold of 25(OH)D for this effect remains unclear. We aimed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training. METHODS: We prospectively followed 1082 RM recruits (males aged 16-32 years) through the 32-week RM training programme. Troops started training between September and July. Height, body weight and aerobic fitness were assessed at week 1. Venous blood samples were drawn at weeks 1, 15 and 32. Serum samples were analysed for 25(OH)D and parathyroid hormone (PTH). RESULTS: Seventy-eight recruits (7.2 %) suffered a total of 92 stress fractures. Recruits with a baseline serum 25(OH)D concentration below 50 nmol L(-1) had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold (chi(2) (1) = 3.564, p = 0.042; odds ratio 1.6 (95 % confidence interval (CI) 1.0-2.6)). Baseline serum 25(OH)D varied from 47.0 +/- 23.7 nmol L(-1) in February, to 97.3 +/- 24.6 nmol L(-1) in July (overall mean 69.2 +/- 29.2 nmol L(-1), n = 1016). There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 (r = -0.209, p < 0.001) and week 32 (r = -0.214, p < 0.001), but not at baseline. CONCLUSION: Baseline serum 25(OH)D concentration below 50 nmol L(-1) was associated with an increased risk of stress fracture. Further studies into the effects of vitamin D supplementation on stress fracture risk are certainly warranted. PMID- 26159114 TI - Oxygen deteriorates arterial function in type 1 diabetes. AB - AIMS: Although oxygen is commonly used to treat various medical conditions, it has recently been shown to worsen vascular function (arterial stiffness) in healthy volunteers and even more in patients in whom vascular function might already be impaired. The effects of oxygen on arterial function in patients with type 1 diabetes (T1D) are unknown, although such patients display disturbed vascular function already at rest. Therefore, we tested whether short-term oxygen administration may alter the arterial function in patients with T1D. METHODS: We estimated arterial stiffness by augmentation index (AIx) and the pulse wave velocity equivalent (SI-DVP) in 98 patients with T1D and 49 age- and sex-matched controls at baseline and during hyperoxia by obtaining continuous noninvasive finger pressure waveforms using a recently validated method. RESULTS: AIx and SI DVP increased in patients (P < 0.05) but not in controls in response to hyperoxia. The increase in AIx (P = 0.05), systolic (P < 0.05), and diastolic (P < 0.05) blood pressure was higher in the patients than in the controls. CONCLUSIONS: Short-term oxygen administration deteriorates arterial function in patients with T1D compared to non-diabetic control subjects. Since disturbed arterial function plays a major role in the development of diabetic complications, these findings may be of clinical relevance. PMID- 26159115 TI - High-sensitivity C-reactive protein, but not white blood cell count, independently predicted incident diabetes in a Japanese health screening population. AB - AIMS: To compare high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) as a predictor of incident diabetes in a population where obesity is not prevalent. METHODS: This is a retrospective 6-year follow-up study in a Japanese health screening population including 1874 men and 1094 women. Using Cox regression methods, hazard ratios (HRs) of incident diabetes for hs-CRP and WBC adjusting for fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other confounders were calculated, and using areas under receiver operating characteristic curve (AUCs), diabetes-predicting abilities of hs-CRP and WBC were compared. Diabetes was defined as FPG >= 126 mg/dL and HbA1c >= 6.5 % or use of antidiabetic medication. RESULTS: During the 6-year follow-up period (mean +/- SD, 4.8 +/- 1.7 years), 71 men (3.8 %) and 19 women (1.7 %) developed incident diabetes. The fully adjusted HRs [95 % confidence intervals (CIs)] of incident diabetes for each 1 SD increase in log hs-CRP and WBC were 1.20 (0.92-1.56) (p = 0.174) and 1.01 (0.78-1.30) (p = 0.946), respectively. The fully adjusted HRs (95 % CIs) of incident diabetes for the highest tertile of hs-CRP and WBC compared with the lowest tertile were 2.57 (1.05-6.27) (p = 0.039) and 1.20 (0.53-2.70) (p = 0.665), respectively. The AUCs (95 % CIs) of hs-CRP and WBC for the discrimination of incident diabetes were 0.73 (0.68-0.77) and 0.67 (0.62-0.72), respectively. CONCLUSIONS: Hs-CRP, but not WBC, was independently associated with incident diabetes in a Japanese health screening population where obesity is not prevalent. PMID- 26159116 TI - Voltage amplification of thermopower waves via current crowding at high resistances in self-propagating combustion waves. AB - Combustion wave propagation in micro/nanostructured materials generates a chemical-thermal-electrical energy conversion, which enables the creation of an unusual source of electrical energy, called a thermopower wave. In this paper, we report that high electrical resistance regimes would significantly amplify the output voltage of thermopower waves, because the current crowding creates a narrow path for charge carrier transport. We show that the structurally defective regions in the hybrid composites of chemical fuels and carbon nanotube (CNT) arrays determine both the resistance levels of the hybrid composites and the corresponding output voltage of thermopower waves. A sudden acceleration of the crowded charges would be induced by the moving reaction front of the combustion wave when the supplied driving force overcomes the potential barrier to cause charge carrier transport over the defective region. This property is investigated experimentally for the locally manipulated defective areas using diverse methods. In this study, thermopower waves in CNT-based hybrid composites are able to control the peak voltages in the range of 10-1000 mV by manipulating the resistance from 10 Omega to 100 kOmega. This controllable voltage generation from thermopower waves may enable applications using the combustion waves in micro/nanostructured materials and better understanding of the underlying physics. PMID- 26159117 TI - Antifogging antireflective thin films: does the antifogging layer have to be the outmost layer? AB - Unusual antifogging antireflective thin films with a maximum transmittance of 98.9% have been realized surprisingly by depositing a hollow silica nanoparticle layer on top of an antifogging polymer layer, which was considered as an irrational design according to the previous knowledge. PMID- 26159118 TI - Assessing Trauma Care Capabilities of the Health Centers in Northern Ghana. AB - INTRODUCTION: Traffic-related injury is a major and increasing cause of global mortality, especially in low- and middle-income countries (LMICs). However, trauma systems, personnel, resources, and infrastructure are frequently insufficient to meet the needs of the population in this at-risk population in LMICs. In addition, these resources are not uniformly distributed, coordinated, nor well described within most countries. Trauma care resources have not previously been characterized in the Northern Region of Ghana. METHODS: We performed uniform site evaluations and interviews at 92 hospitals in Northern Ghana. Trauma systems, material resources, and human resources were quantified. Equipment was characterized as available in the Emergency Department (ED), in the hospital only, or unavailable. Hospitals were categorized as primary, district, or referral. RESULTS: Forty-two primary hospitals, 48 district hospitals, 3 regional hospitals, and 1 teaching hospital were surveyed. Over 95 % of hospitals reported having no training or systems for the care of injured patients. Substantial clinical equipment deficits were found at most primary hospitals. In over 90 % of these hospitals, the majority of circulation and monitoring, airway and breathing, and diagnostic imagining resources were not available. Equipment was also frequently unavailable at district and regional hospitals. When available, these resources were infrequently present in the ED. CONCLUSIONS: Although resources may be unavoidably constrained, there are substantial opportunities to improve the systematic management of trauma care and improve the education of the medical providers regarding care of injured patients in the region studied. PMID- 26159119 TI - Risk Factors and Managements of Bile Leakage After Hepatectomy. AB - BACKGROUND: The purpose of this study was to retrospectively determine the risk factors and evaluate the management of bile leakage. METHODS: Three hundred and thirty-four patients who underwent hepatectomy for Child classification grade A liver disease, without biliary reconstruction and laparoscopic procedures, between 2003 and 2013 were included. Risk factors were identified using multivariate analysis. RESULTS: Bile leakage was observed in 30 (9.0%) patients. Multivariate analysis demonstrated that type of hepatectomy (segmentectomy 1, medial sectionectomy, anterior sectionectomy, or central bisectionectomy) and operating time was independent risk factors for bile leakage. Among 30 patients with confirmed bile leakage, central type leakage that was in communication with the biliary tree occurred in 23 (76.7%) patients and peripheral type, which was not in communication with the biliary tree, in 7 (23.3%) patients. Ten patients were treated with only drainage. Endoscopic or percutaneous transhepatic procedures were performed in 15 cases with central type leakage. Ablation treatment using ethanol or minocycline was mainly performed for peripheral type leakage. Four cases with central type leakage had strictures of the right hepatic duct. Two of them were treated with ablation treatment, portal vein embolization, or fistulojejunostomy. Median duration from diagnosis to end of therapy was 77 days (11-323) in central type and 44 days (6-123) in peripheral type leakage, respectively. CONCLUSIONS: Complex hepatectomy and operating time are independent risk factors for postoperative bile leakage. Biliary exploration should be performed as soon as possible after diagnosis, because most bile leakage is the central type. Central type of bile leakage is sometimes refractory to therapy, needing various treatments and requiring a long time for recovery. PMID- 26159121 TI - Centrifugation-assisted Assembly of Colloidal Silica into Crack-Free and Transferrable Films with Tunable Crystalline Structures. AB - Self-assembly of colloidal particles into colloidal films has many actual and potential applications. While various strategies have been developed to direct the assembly of colloidal particles, fabrication of crack-free and transferrable colloidal film with controllable crystal structures still remains a major challenge. Here we show a centrifugation-assisted assembly of colloidal silica spheres into free-standing colloidal film by using the liquid/liquid interfaces of three immiscible phases. Through independent control of centrifugal force and interparticle electrostatic repulsion, polycrystalline, single-crystalline and quasi-amorphous structures can be readily obtained. More importantly, by dehydration of silica particles during centrifugation, the spontaneous formation of capillary water bridges between particles enables the binding and pre shrinkage of the assembled array at the fluid interface. Thus the assembled colloidal films are not only crack-free, but also robust and flexible enough to be easily transferred on various planar and curved substrates. PMID- 26159122 TI - The influence of curricula and role models on medical students' professional self identification: a reminder call. PMID- 26159123 TI - Collision cross sections of high-mannose N-glycans in commonly observed adduct states--identification of gas-phase conformers unique to [M-H](-) ions. AB - We report collision cross sections (CCS) of high-mannose N-glycans as [M + Na](+), [M + K](+), [M + H](+), [M + Cl](-), [M + H2PO4](-) and [M - H](-) ions, measured by drift tube (DT) ion mobility-mass spectrometry (IM-MS) in helium and nitrogen gases. Further analysis using traveling wave (TW) IM-MS reveal the existence of distinct conformers exclusive to [M - H](-) ions. PMID- 26159120 TI - Tube Thoracostomy: A Structured Review of Case Reports and a Standardized Format for Reporting Complications. AB - INTRODUCTION: Although seemingly straightforward, tube thoracostomy (TT) has been associated with complication rates as high as 30 %. A lack of a standardized nomenclature for reporting TT complications makes comparison and evaluation of reports impossible. We aim to develop a classification method in order to standardize the reporting of complications of TT and identify all reported complications of TT and time course in which they occurred to validate the reporting method. METHODS: A systematic search of MEDLINE, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews from each databases inception through November 5, 2013 was conducted. Original articles written in the English language reporting TT complications were searched. This review adhered to preferred reporting items for systematic reviews and meta-analyses (PRISMA) standards. Duplicate reviewers abstracted case reports for inclusion. Cases were then sorted into one of the five complication categories by two reviewers, and in case of disagreements, settled by a third reviewer. RESULTS: Of 751 papers reporting TT complications, 124 case reports were included for analysis. From these reports, five main categories of TT complications were identified: insertional (n = 65); positional (n = 36); removal (n = 11); infective and immunologic (n = 7); and instructional, educational, or equipment related (n = 5). Placement of TT has occurred in nearly every soft tissue and vascular structure in the thoracic cavity and intra-abdominal organs. CONCLUSION: Our classification method provides further clarity and systematic standardization for reporting TT complications. PMID- 26159125 TI - Posterior Vertical Bite Reconstructions of Erosively Worn Dentitions and the "Stamp Technique" - A Case Series with a Mean Observation Time of 40 Months. AB - PURPOSE: In the present case series, the authors report on seven cases of erosively worn dentitions (98 posterior teeth) which were treated with direct resin composite. MATERIALS AND METHODS: In all cases, both arches were restored by using the so-called stamp technique. All patients were treated with standardized materials and protocols. Prior to treatment, a waxup was made on die cast models to build up the loss of occlusion as well as ensure the optimal future anatomy and function of the eroded teeth to be restored. During treatment, teeth were restored by using templates of silicone (ie, two "stamps," one on the vestibular, one on the oral aspect of each tooth), which were filled with resin composite in order to transfer the planned, future restoration (ie, in the shape of the waxup) from the extra- to the intraoral situation. Baseline examinations were performed in all patients after treatment, and photographs as well as radiographs were taken. To evaluate the outcome, the modified United States Public Health Service criteria (USPHS) were used. RESULTS: The patients were re assessed after a mean observation time of 40 months (40.8 +/- 7.2 months). The overall outcome of the restorations was good, and almost exclusively "Alpha" scores were given. Only the marginal integrity and the anatomical form received a "Charlie" score (10.2%) in two cases. CONCLUSION: Direct resin composite restorations made with the stamp technique are a valuable treatment option for restoring erosively worn dentitions. PMID- 26159124 TI - Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells. AB - Cardiac cell therapies involving bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promising results, although their mechanisms of action are still poorly understood. Here, we investigated direct interactions between hMSCs and cardiomyocytes in vitro. Using a genetic Ca(2+) indicator gCaMP3 to efficiently label hMSCs in co-cultures with neonatal rat ventricular myocytes (NRVMs), we determined that 25-40% of hMSCs (from 4 independent donors) acquired periodic Ca(2+) transients and cardiac markers through spontaneous fusion with NRVMs. Sharp electrode and voltage-clamp recordings in fused cells showed action potential properties and Ca(2+) current amplitudes in between those of non-fused hMSCs and NRVMs. Time-lapse video-microscopy revealed the first direct evidence of active fusion between hMSCs and NRVMs within several hours of co-culture. Application of blebbistatin, nifedipine or verapamil caused complete and reversible inhibition of fusion, suggesting potential roles for actomyosin bridging and Ca(2+) channels in the fusion process. Immunostaining for Cx43, Ki67, and sarcomeric alpha-actinin showed that fused cells remain strongly coupled to surrounding NRVMs, but downregulate sarcomeric structures over time, acquiring a non-proliferative and non-contractile phenotype. Overall, these results describe the phenotype and mechanisms of hybrid cell formation via fusion of hMSCs and cardiomyocytes with potential implications for cardiac cell therapy. PMID- 26159126 TI - Biomechanical Behavior of Extensively Restored Premolars: Cusp Deformation, Marginal Integrity, and Fracture Resistance. AB - PURPOSE: To study the biomechanical behavior of extensively restored premolars by determining the effect of the composite type, presence of cusp weakening, and compressive loading on the cusp deformation (CD), marginal integrity (MI), and fracture resistance (FR) of directly restored premolars. MATERIALS AND METHODS: Forty premolars received Class II mesio-occlusal-distal (MOD) cavities and were divided into 4 groups (n = 10) in accordance with the two study variables: composite type (conventional: Filtek Z250 XT [Z250], 3M ESPE; low shrinkage: Venus Diamond [VD], Heraeus-Kulzer) and the presence of cusp weakening (with/without). Cusp deformation upon restoration was assessed using strain gauges during the restorative procedure and thereafter when the restorations were subjected to an occlusal load of 100 N. The samples were subjected to thermal and mechanical cycling. Epoxy resin replicas of the proximal tooth/restoration interfaces were made to analyze the marginal integrity (MI) using scanning electron microscopy. To determine the fracture resistance (FR), the teeth were loaded at a crosshead speed of 0.5 mm/min until fracture. RESULTS: The conventional composite Z250 had higher CD, lower MI, and lower FR than the low shrinkage composite VD. Cusp weakening had no influence on CD, but MI and FR decreased. CONCLUSION: The low-shrinkage composite VD performed better in restoring extensively destroyed premolars than did Z250. PMID- 26159127 TI - Effect of Solvents on Dentin Collagen Cross-linking Potential of Carbodiimide. AB - PURPOSE: This study compared the dentin collagen cross-linking potential of carbodiimide (EDC) prepared in three most commonly used solvents in dental adhesive systems: water, ethanol, and acetone. MATERIALS AND METHODS: Thirty eight extracted caries-free human permanent molars were used in this study. Demineralized dentin beams were prepared and cross linked by 0.3 M EDC in water, acetone, or ethanol. The modulus of elasticity of demineralized dentin, the resistance of dentin matrix to enzymatic degradation, the swelling ratio, and the mass change of demineralized dentin matrix were examined to compare the cross linking efficacy of EDC in their respective solvents. RESULTS: The modulus of elasticity of demineralized dentin cross linked by EDC in acetone was significantly higher (p < 0.05) than demineralized dentin cross linked by EDC in ethanol and EDC in water. Furthermore, the ultimate tensile strength of demineralized dentin cross linked by EDC in water and ethanol dropped significantly following enzymatic degradation, while the ultimate tensile strength of demineralized dentin cross linked by EDC in acetone was preserved. The swelling ratio of demineralized dentin cross linked by EDC in acetone and ethanol was significantly lower (p < 0.05) than that of demineralized dentin cross linked by EDC in water. Conversely, the mass change of demineralized dentin cross linked by EDC in acetone was significantly higher (p < 0.05) than demineralized dentin cross linked by EDC in water and EDC in ethanol. CONCLUSION: The dentin collagen cross-linking potential of EDC could be enhanced by using acetone as a solvent. PMID- 26159128 TI - Long-term Adhesion Study of Self-etching Systems to Plasma-treated Dentin. AB - PURPOSE: To determine the influence of atmospheric pressure plasma (APP) treatment on the microtensile dentin bond strength of two self-etching adhesive systems after one year of water storage as well as observe the contact angle changes of dentin treated with plasma and the micromorphology of resin/dentin interfaces using SEM. MATERIALS AND METHODS: For contact angle measurements, 6 human molars were sectioned to remove the occlusal enamel surface, embedded in PMMA resin, and ground to expose a flat dentin surface. Teeth were divided into two groups: 1) argon APP treatment for 30 s, and 2) blown air (control). For the microtensile test, 28 human third molars were used and prepared similarly to contact angle measurements. Teeth were randomly divided into 4 groups (n = 7) according to two self-etching adhesives and APP treatment (with/without). After making the composite resin buildup, teeth were sectioned perpendicular to the bonded interface to obtain beam specimens. The specimens were tested after 24 h and one year of water storage until failure. Bond strength data were analyzed by three-way ANOVA and Tukey's post-hoc test (alpha = 0.05%). Three beam specimens per group that were not used in the bond strength test were prepared for interfacial SEM analysis. RESULTS: APP application decreased the contact angle, but increased the bond strength only for one adhesive tested. SEM evaluation found signs of degradation within interfacial structures following 1-year aging in water. APP increased the dentin surface energy, but the effects of APP and 1 year water storage on dentin bond strength were product dependent. CONCLUSION: APP increased the dentin surface energy. It also increased the bond strength for Scotchbond Universal, but storage for one year negated the positive effect of APP treatment. PMID- 26159129 TI - Long-term Bond Strength between Layering Indirect Composite Material and Zirconia Coated with Silicabased Ceramics. AB - PURPOSE: This study evaluated the long-term shear bond strength between an indirect composite material and a zirconia framework coated with silica-based ceramics, taking the effect of different primers into account. MATERIALS AND METHODS: A total of 165 airborne-particle abraded zirconia disks were subjected to one of three pretreatments: no pretreatment (ZR-AB), airborne-particle abrasion of zirconia coated with feldspathic porcelain (ZR-PO-AB), and 9.5% hydrofluoric acid etching of zirconia coated with feldspathic porcelain (ZR-PO HF). An indirect composite material (Estenia C&B) was then bonded to the zirconia disks after they were treated with one of the following primers: Clearfil Photo Bond (CPB), Clearfil Photo Bond with Clearfil Porcelain Bond Activator (CPB + Activator), Estenia Opaque Primer (EOP), Porcelain Liner M Liquid B (PLB), or no priming (CON, control group). Shear bond strength was tested after 100,000 thermocycles, and the data were analyzed using the Steel-Dwass U-test (alpha = 0.05). RESULTS: For ZR-PO-AB and ZR-PO-HF specimens, bond strength was highest in the CPB+Activator group (25.8 MPa and 22.4 MPa, respectively). Bond strengths were significantly lower for ZR-AB specimens in the CON and PLB groups and for ZR PO-AB specimens in the CON, CPB, and EOP groups. CONCLUSION: Combined application of a hydrophobic phosphate monomer (MDP) and silane coupling agent enhanced the long-term bond strength of indirect composite material to a zirconia coated with silica-based ceramics. PMID- 26159130 TI - Influence of 3-month Simulated Pulpal Pressure on the Microtensile Bond Strength of Simplified Resin Luting Systems. AB - PURPOSE: To assess the influence of simulated pulpal pressure (SPP) on the microtensile bond strength (MUTBS) of four simplified luting strategies to indirect composite restorations. MATERIALS AND METHODS: Dentin disks from 40 human molars were prepared and treated with 4 different techniques: (1) SB+ARC: two-step etch-and-rinse adhesive + conventional dual-curing resin cement (Adper Single Bond 2 + RelyX ARC, 3M ESPE); (2) ED+PAN: self-etching primer + conventional dual-curing resin cement (ED Primer + Panavia F2.0, Kuraray Medical); (3) S3+PAN: one-step self-etching adhesive (Clearfil S3, Kuraray) + Panavia F2.0; (4) U200: self-adhesive resin cement (RelyX U200, 3M ESPE). Pre made indirect composite restorations (Filtek Z100, 3M ESPE) were luted onto the specimens. The luted specimens were cut into resin-dentin beams and the MUTBS was tested after two different aging regimes: water storage at 37 degrees C for one week (control) or three months under 20 cm H2O simulated pulpal pressure (SPP). The MUTBS data was analyzed with two-way ANOVA and Tukey's test (p < 0.05). RESULTS: SB+ARC showed significantly higher MUTBS after both aging regimes (p < 0.001). The statistically significantly lowest MUTBS was measured for control S3+PAN and U200 after 3 months SPP (p < 0.001). S3+PAN was the only group not negatively affected by SPP (p = 0.699). CONCLUSIONS: Two-step etch-and-rinse adhesives associated with dual-curing conventional resin cements may achieve the highest MUTBS, even after 3 months of SPP. The one-step self-etching adhesive along with the dualcuring conventional resin cement was able to maintain bond stability. PMID- 26159131 TI - A Structure-Activity Relationship Study of Naphthoquinone Derivatives as Antitubercular Agents Using Molecular Modeling Techniques. AB - Tuberculosis (TB) is one of the major causes of death worldwide. Mycobacterium tuberculosis, the leading causative agent of TB, is responsible for the morbidity and mortality of a large population worldwide. In view of above and as a part of our effort to develop new and potent anti-TB agents, a series of substituted naphthoquinone derivatives were subjected to molecular modeling using various feature selection methods. The statistically significant best 2D-QSAR model having correlation coefficient [Formula: see text] and cross-validated squared correlation coefficient [Formula: see text] with external predictive ability of [Formula: see text] was developed by SA-PLS, and group-based QSAR model having [Formula: see text] and [Formula: see text] with [Formula: see text] was developed by SA-PLS. Further analysis using three-dimensional QSAR technique identifies a suitable model obtained by SA-partial least square method leading to antitubercular activity prediction. k-nearest neighbor molecular field analysis was used to construct the best 3D-QSAR model using SA-PLS method, showing good correlative and predictive capabilities in terms of [Formula: see text] and [Formula: see text]. The pharmacophore analysis results obtained from this study show that the distance between the aromatic/hydrophobic and the naphthoquinone moiety sites to the aliphatic and acceptor groups should be connected with almost the same distance for significant antitubercular activity. The information rendered by QSAR models may lead to a better understanding of structural requirements of antitubercular activity and also can help in the design of novel potent antitubercular activity. PMID- 26159132 TI - [Bioethical Approach for Nursing Research -Focused on the Use of Research Ethics Committees]. AB - PURPOSE: This paper was written to introduce methods of using the research ethics committee (RES) from requesting the initial review to reporting the close-out for nursing researchers. METHODS: General ethical principles were described by reviewing the 'Bioethics and Safety Act' and other related guidelines, and constructing some questions and answers. RESULTS: The results were composed of three parts; definition of RES, steps in using RES, and archiving. The 7 steps for using RES were; identifying whether the study needed to be reviewed, by the RES identifying whether the study could be exempted, requesting the initial review after preparing documents, requesting the re-review, requesting an amendment review, requesting a continuing review and reporting the close-out. CONCLUSION: Nursing researchers need to receive RES approval before starting nursing research involving human subjects. Nursing researchers are urged to use the steps reported in this paper to receive RES approval easily and quickly. PMID- 26159133 TI - Methodological Issues in Questionnaire Design. AB - PURPOSE: The process of designing a questionnaire is complicated. Many questionnaires on nursing phenomena have been developed and used by nursing researchers. The purpose of this paper was to discuss questionnaire design and factors that should be considered when using existing scales. METHODS: Methodological issues were discussed, such as factors in the design of questions, steps in developing questionnaires, wording and formatting methods for items, and administrations methods. How to use existing scales, how to facilitate cultural adaptation, and how to prevent socially desirable responding were discussed. Moreover, the triangulation method in questionnaire development was introduced. RESULTS: Steps were recommended for designing questions such as appropriately operationalizing key concepts for the target population, clearly formatting response options, generating items and confirming final items through face or content validity, sufficiently piloting the questionnaire using item analysis, demonstrating reliability and validity, finalizing the scale, and training the administrator. Psychometric properties and cultural equivalence should be evaluated prior to administration when using an existing questionnaire and performing cultural adaptation. CONCLUSION: In the context of well-defined nursing phenomena, logical and systematic methods will contribute to the development of simple and precise questionnaires. PMID- 26159134 TI - [Factors Influencing Physical Activity among Community-dwelling Older Adults with Type 2 Diabetes: A Path Analysis]. AB - PURPOSE: The purpose of the study was to identify factors influencing physical activity among community-dwelling older adults with type 2 diabetes. The study design was based on the Theory of Triadic Influence. METHODS: A total of 242 older adults with type 2 diabetes participated in this study. Six variables related to physical activity in older adults, including self-efficacy, social normative belief, attitudes, intention, experience, and level of physical activity, were measured using reliable instruments. Data were analyzed using descriptive statistics, Pearson's correlation analyses, and a path analysis. RESULTS: The mean physical activity score was 104.2, range from zero to 381.21. The path analysis showed that self-efficacy had the greatest total effect on physical activity. Also, experience had direct and total effects on physical activity as well as mediated the paths of social normative beliefs to attitudes and intention to physical activity. These factors accounted for 10% of the total variance, and the fit indices of the model satisfied the criteria of fitness. CONCLUSION: The findings of the study reveal the important role of self-efficacy and past experience in physical activity in older adults with type 2 diabetes. PMID- 26159135 TI - [Effects of a Mobile Web-based Pregnancy Health Care Educational Program for Mothers at an Advanced Maternal Age]. AB - PURPOSE: This study was conducted to develop a mobile web-based pregnancy health care educational program for mothers who were at an advanced maternal age (AMA) and to verify the effects of the program on pregnancy health care. METHODS: This program was developed using a web-based teaching-learning system design model and composed of 10 subject areas. This research was a quasi-experimental study using a non-equivalent control group pretest-posttest time serial design and data were collected from April 2 to May 3, 2014. To verify the effects of the program, it was used for 2 weeks with 30 AMA mothers (experimental group). For the control group, a classroom education booklet for pregnant women used with 31 AMA mothers. RESULTS: The experimental group having participated in program had statistically significantly higher scores for knowledge (t=3.76, p<.001), self-efficacy (t=8.54, p<.001), and practice behavior (t=4.88, p<.001) of pregnancy health care, compared to the control group. CONCLUSION: The results of the program indicate that a Mobile web-based pregnancy health care educational program is effective in meeting the needs of AMA mothers and can be used as the prenatal educational program for AMA mothers and is appropriate as an educational media for theses mothers. PMID- 26159136 TI - [Effectiveness of the Self-determination Theory based a Motivational Interviewing YOU-TURN Program for Smoking Cessation among Adolescents]. AB - PURPOSE: In this study, the effectiveness of a motivational interviewing smoking cessation YOU-TURN program for adolescents was examined. The program was based on the self-determination theory. METHODS: The study was carried out with a nonequivalent control group pretest-posttest design. Participants in the present study were 136 high school students living in D city. The students were assigned to the experimental group (n=52) who participated in the motivational interviewing smoking cessation YOU-TURN program based on self-determination theory, or to the control group (n=84) who participated in a general smoking cessation program. Data were collected from September 1, 2013 through April 30, 2014. Collected data were analyzed using SPSS PC+ 21.0 with Chi-square test, Fisher's exact test, t-test, Mann-Whitney U test, Repeated Measures ANOVA, and MANOVA-Wilk's Lambda. RESULTS: The experimental group had a significant increase in basic psychological needs, and duration of quitting-smoking in comparison with the control group. The experimental group had a significant decrease in cigarettes smoked per day and cotinine in urine in comparison with the control group. CONCLUSION: The motivational interviewing YOU-TURN program, when delivered to adolescents who smoked, was effective in discouraging smoking, and can be utilized as an effective nursing intervention for adolescents who smoke. PMID- 26159137 TI - [Adaptation and Evaluation of the Incontinence Care Protocol]. AB - PURPOSE: This study was done to develop an evidence-based incontinence care protocol through an adaptation process and to evaluate the effects of the protocol. METHODS: The protocol was developed according to the guideline of adaptation. A non-randomized controlled trial was used for testing the effects of the new Incontinence Care Protocol. A total of 120 patients having bowel incontinence with Bristol stool type 5, 6, and 7 and admitted to intensive care units were recruited to this study. The newly developed incontinence care protocol was used with patients in the experimental group and conventional skin care was given to patients in the control group. Outcome variables were incontinence-associated dermatitis (IAD) severity, pressure ulcer occurrence and severity. RESULTS: The experimental group had significantly less severe IAD (t=6.69, p<.001), lower occurrence of pressure ulcers (chi2=7.35, p=.007), and less severity of pressure ulcers (Mann-Whitney=86.00, p=.009) than the control group. CONCLUSION: Use of this incontinence care protocol has the effects of preventing pressure ulcers and inhibiting worsening of IAD and pressure ulcers. Therefore, this incontinence care protocol is expected to contribute to managing IAD and pressure ulcers. PMID- 26159138 TI - [Effects of Blending Oil of Lavender and Thyme on Oxidative Stress, Immunity, and Skin Condition in Atopic Dermatitis Induced Mice]. AB - PURPOSE: The purpose of this study was to evaluate the effects of essential oil on oxidative stress, immunity, and skin condition in atopic dermatitis (AD) induced mice. METHODS: This study was a 3*3 factorial design. Factors were oil type (Lavender, Thyme, and 2:1 mixture of lavender and thyme oil [blending oil]) and treatment period (0 day, 7 days, and 21 days). The samples were 45 mice with AD and randomly assigned to nine groups of five mice per group. The dependent variables such as superoxide radical, IgE, degranulated mast cells, and epidermal thickness were measured. Data were collected from February to April in 2014. Descriptive statistics, One-way ANOVA, Two-way ANOVA, and Tukey's HSD test were performed using the SPSS WIN 20.0 program. RESULTS: Dependent variables were not statistically significantly different by the three oil types (p>.05). Essential oils such as lavender, thyme, and blending oil were all effective in reducing AD symptoms and especially 2:1 blending oil were most effective. There were statistically significant differences by the three treatment periods in all dependent variables (p<.001). There were statistically significant interactions between oil types and treatment periods in all dependent variables (p<.01). For decreasing superoxide radical, degranulated mast cells, and epidermal thickness, 2:1 mixed oil should be applied for at least 21 days. Otherwise to reduce IgE, 2:1 mixed oil should be used for at least 7 days. CONCLUSION: These findings provide bases for developing effective interventions for AD patients to manage their AD symptoms. PMID- 26159139 TI - [Symptom Clusters in Korean Patients with Acute Myocardial Infarction]. AB - PURPOSE: Acute myocardial infarction (AMI) leads to death if the patient does not receive emergency treatment. Thus it is very important to recognize the symptoms in the early stage. The purpose of this study was to identify clusters of symptoms that represent AMI in Koreans. METHODS: The study used a retrospective, descriptive design with secondary data analysis. Data were abstracted from 725 medical records of AMI patients admitted from June 1, 2006 to August 15, 2014 at a university hospital. RESULTS: Analysis of the AMI symptoms revealed five symptom clusters; Cluster 1 (n=140): middle chest pain (100%), shortness of breath, and cold sweating, Cluster 2 (n=256): substernal pain (100%), cold sweating, and shortness of breath, Cluster 3 (n=47): substernal pain (95.7%), left arm pain, shortness of breath, cold sweating, left shoulder pain, right arm pain, and the lower neck pain, Cluster 4 (n=212): shortness of breath (28.3%), left chest pain, and upper abdominal pain, and Cluster 5 (n=70): cold sweating (100%), left chest pain, shortness of breath, left shoulder pain, and upper abdominal pain. Length of hospital stay and mortality rate were significantly different according to symptom clusters (F=2.52, p=.040; F=3.62, p=.006, respectively). CONCLUSION: Symptom clusters of AMI from this study can be used for AMI patients in order to recognize their symptoms at an early stage. The study findings should be considered when developing educational prevention programs for Koreans with AMI. PMID- 26159140 TI - [Effects of Silver-Care-Robot Program on Cognitive Function, Depression, and Activities of Daily Living for Institutionalized Elderly People]. AB - PURPOSE: The purpose of this study was to identify the effects on cognitive function, depression, and activities of daily living of Silver-Care-Robot Program for institutionalized elders. METHODS: This study was a nonequivalent control group pretest-posttest design. The participants were 42 institutionalized elders (17 in the experimental group and 25 in the control group). The Silver-Care-Robot Program was provided as an intervention which was conducted twice a week for 5 weeks. The Silver-Care-Robot Program is an integrated entertainment program to help the mental, emotional, and physical health of elderly people. Pre-test was conducted on the two groups, and, in order to examine the effects of intervention, a post-test was conducted after 5 weeks. RESULTS: There were significant differences in cognitive function and ADL (activities of daily living) between two groups after the program. But the difference in depression in the institutionalized elders was not statistically significant between the two groups. CONCLUSION: The Silver-Care-Robot Program should be considered as a regular program for cognitive function and activities of daily living for institutionalized elders. PMID- 26159141 TI - [Experience of College Students on Suicide Attempts]. AB - PURPOSE: The purpose of the study was to explore and describe the experience of Korean college students on suicide attempts. METHODS: Eight students participated and data were collected through in-depth individual interviews between September, 2011 and April, 2012. Data were analyzed using Strauss and Corbin's grounded theory method. RESULTS: Analysis showed that the central phenomenon of suicide attempt experience of college students was 'inextricable despair'. Causal conditions were 'sense of shame by failure to achieve perfect independence' and 'a big gap between reality and ideals'. Contextual conditions were 'extreme situation of being cornered' and 'excessive changes in emotions'. Intervening conditions were 'important others' and 'perspectives on the world'. Action/interaction strategies were 'temporary efforts' and 'gathering up one's mind'. Consequences were 'trauma as one's own hurt', 'conflict between life and death' and 'becoming mature'. CONCLUSION: The results of this study provide an in depth understanding of the experience of college students with attempted suicide. It is necessary to develop programs to prevent suicide attempts by college students and these results can be used as a basis for program development. PMID- 26159142 TI - [Validity and Reliability of the Person-centered Care Assessment Tool in Long term Care Facilities in Korea]. AB - PURPOSE: The aim of this study was to evaluate the validity and reliability of the Korean version of the Person-centered Care Assessment Tool (P-CAT). METHODS: The English P-CAT was translated into Korean with forward and backward translation. Survey data were collected from 458 staff in 17 long-term care facilities in Korea. Construct validity and criterion related validity were evaluated. Cronbach's alpha was used to assess reliability. RESULTS: The Korean version of P-CAT was shown to be valid homogeneously by factor, item and content analysis. Internal consistency reliability was satisfactory in which the values of factor 1, factor 2 and the total scale were .84, .77 and .86 respectively. Exploratory factor analysis supported the construct validity with a two-factor solution. Factor loadings of the 13 items ranged in .34~.80. Criterion validity to the Person-centered Climate Questionnaire-staff (PCQ-S) was .74 (p<.001). CONCLUSION: The Korean version of the P-CAT was found to be an applicable instrument with satisfactory reliability and validity for further use in measuring successful person-centered care in long-term care facilities for older persons. PMID- 26159143 TI - [Factors associated with Self-Rated Health in Metabolic Syndrome and Relationship between Sleep Duration and Metabolic Syndrome Risk Factors]. AB - PURPOSE: Purpose was to explore associations between sleep duration and metabolic syndrome (MS) risks, and to determine factors associated with self-rated health (SRH) of adults with MS compared to other adults. METHODS: This is a secondary data analysis based on the Fifth Korea National Health and Nutrition Examination Survey KNHANES V (N=12662). Study instruments included sleep duration, MS risk factors, SRH and health-related quality of life (HRQoL). RESULTS: Mean age of participants was 43.68+/-12.26 years. Fifty-eight percent were women, and 18.3% were identified as having MS. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and SRH were significantly different according to sleep duration (p<.05) among all participants. In the non MS group, male gender, younger age (19~30 and 41~50 age brackets) upper income level, sufficient sleep duration, and high density lipoprotein (HDL) were positively associated with SRH, whereas, lower education levels (<=middle school), glucose level, and waist circumference were negatively associated with SRH (p<.05). In the MS group, lower income, lower education levels (<=middle school), glucose level, and waist circumference were negatively associated with SRH, whereas, having an occupation was positively associated with SRH (p<.05). CONCLUSION: Results suggest that tailored approaches are required for prevention and control of MS and sleep duration of each individual should be considered rather than applying standardized guidelines. However, as sleep quality was not included in the analysis, further investigations regarding influence of sleep quality on MS and SRH and controlling for other lifestyle and health behavior factors are required. PMID- 26159144 TI - [Development and Application of a Performance Prediction Model for Home Care Nursing Based on a Balanced Scorecard using the Bayesian Belief Network]. AB - PURPOSE: This study was conducted to develop key performance indicators (KPIs) for home care nursing (HCN) based on a balanced scorecard, and to construct a performance prediction model of strategic objectives using the Bayesian Belief Network (BBN). METHODS: This methodological study included four steps: establishment of KPIs, performance prediction modeling, development of a performance prediction model using BBN, and simulation of a suggested nursing management strategy. An HCN expert group and a staff group participated. The content validity index was analyzed using STATA 13.0, and BBN was analyzed using HUGIN 8.0. RESULTS: We generated a list of KPIs composed of 4 perspectives, 10 strategic objectives, and 31 KPIs. In the validity test of the performance prediction model, the factor with the greatest variance for increasing profit was maximum cost reduction of HCN services. The factor with the smallest variance for increasing profit was a minimum image improvement for HCN. During sensitivity analysis, the probability of the expert group did not affect the sensitivity. Furthermore, simulation of a 10% image improvement predicted the most effective way to increase profit. CONCLUSION: KPIs of HCN can estimate financial and non financial performance. The performance prediction model for HCN will be useful to improve performance. PMID- 26159145 TI - Psychometric Properties of the Korean Version of the HIV Self-Management Scale in Patients with HIV. AB - PURPOSE: The purpose of this study was to examine validity and reliability of Webel and colleagues' HIV Self-Management Scale when used with a Korean sample. METHODS: The original 20-item HIV Self-Management Scale was translated into Korean using translation and back-translation. Nine HIV nurse experts tested content validity. Principal component analysis (PCA) and confirmatory factor analysis (CFA) of data from 203 patients was used to test construct validity. Concurrent validity was evaluated using correlation with patients' self-rating as a "smart patient" measured using a visual analogue scale. Internal consistency was tested by Cronbach's alpha coefficients. RESULTS: All items were rated as having satisfactory content validity. Based on PCA and consideration of conceptual meaning, a three-factor solution was selected, explaining 48.76% of the variance. CFA demonstrated the adequacy of the three-domain structure of the construct HIV self-management: daily self-management health practices, social support and HIV self-management, and chronic nature of HIV self-management. Goodness-of-fit indices showed an acceptable fit overall with the full model (chi2/df(164)=1.66, RMSEA=0.06, SRMR=0.05, TLI=0.91, and CFI=0.92). The Korean version of the HIV Self-Management Scale (KHSMS) was significantly correlated with patients' self-rated smart patient (r=.41). The subscale Cronbach's alpha coefficients ranged from .78 to .81; alpha for the total scale was .89. CONCLUSION: The KHSMS provides a valid and reliable measure of self-management in Korean patients with HIV. Continued psychometric testing is recommended to provide further evidence of validity with this population. PMID- 26159146 TI - Associations of Breastfeeding Knowledge, Attitude and Interest with Breastfeeding Duration: A Cross-sectional Web-based Study. AB - PURPOSE: Maternal knowledge, positive attitudes and interest toward breastfeeding may improve the sustainability of breastfeeding. This study examined the associations of knowledge, attitudes, and interest toward breastfeeding with the duration of breastfeeding in Korean mothers who used the internet. METHODS: We conducted a cross-sectional study of 604 Korean mothers who breastfed their babies. Mothers were recruited through the internet and their knowledge, attitudes and interest toward breastfeeding were assessed using a web-based self administered questionnaire. Geometric means and odds ratio (OR) with 95% confidence intervals were calculated. RESULTS: Higher knowledge, attitudes, and interest toward breastfeeding were associated with longer duration of breastfeeding in Korean mothers. In particular, mothers who had optimal breastfeeding duration were more likely to be aware of the easiness of breast milk stimulation and breastfeeding, the development of attachment between mother and child, and pleasure from breastfeeding compared to those mothers with shorter duration. The association with optimal breastfeeding duration was more pronounced among mothers who graduated from high school for total attitude scores and total interest scores, compared to mothers who graduated from college or above. CONCLUSION: The results of this study suggest that it is important to improve maternal knowledge, attitudes, and interest toward breastfeeding in Korean mothers who use the internet as a source of knowledge. Also, the study results imply that the development of strategies to target mothers with relatively low education levels may improve breastfeeding rates. PMID- 26159147 TI - Wheel of Wellness Counseling in Community Dwelling, Korean Elders: A Randomized, Controlled Trial. AB - PURPOSE: The purpose of this study was to investigate the effects of Wheel of Wellness counseling on wellness lifestyle, depression, and health-related quality of life in community dwelling elderly people. METHODS: A parallel, randomized controlled, open label, trial was conducted. Ninety-three elderly people in a senior welfare center were randomly assigned to two groups: 1) A Wheel of Wellness counseling intervention group (n=49) and 2) a no-treatment control group (n=44). Wheel of Wellness counseling consisted of structured, individual counseling based on the Wheel of Wellness model and provided once a week for four weeks. Wellness lifestyle, depression, and health-related quality of life were assessed pre-and post-test in both groups. RESULTS: Data from 89 participants were analyzed. For participants in the experimental group, there was a significant improvement on all of the wellness-lifestyle subtasks except realistic beliefs. Perceived wellness and depression significantly improved after the in the experimental group (n=43) compared to the control group (n=46) from pre- to post-test in the areas of sense of control (p=.033), nutrition (p=.017), exercise (p=.039), self-care (p<.001), stress management (p=.017), work (p=.011), perceived wellness (p=.019), and depression (p=.031). One participant in the intervention group discontinued the intervention due to hospitalization and three in the control group discontinued the sessions. CONCLUSION: Wheel of Wellness counseling was beneficial in enhancing wellness for the community-dwelling elderly people. Research into long-term effects of the intervention and health outcomes is recommended. PMID- 26159148 TI - Prevalence and Correlates of School Bullying Victimization in Xi'an, China. AB - This study used the data from a representative sample to estimate the prevalence of child bullying victimization in Xi'an, China. Data on social demographic information and the experiences of different types of bullying victimization were collected from a randomly selected sample with 3,175 middle school students aged 15-17 years by self-administrated questionnaires. t Test, chi2 test, and multiple logistic regression analyses were used to test group differences and examine the correlates of bullying victimization. Results show that 54.9% and 44.6% of Chinese children have been bullied in a lifetime and in the preceding year, respectively. Correlates for direct and relational bullying victimization includes male participants, father's lower education level, father's unemployment, having one or more siblings, smoking, depression, borderline personality trait, posttraumatic stress disorder, and from rural schools. Overall, the prevalence of child bullying victimization in China is substantial. The multiple correlates suggest prevention and intervention of bullying victimization in a holistic and comprehensive way. PMID- 26159149 TI - Vaccination coverage in French 17-year-old young adults: an assessment of mandatory and recommended vaccination statuses. AB - We aimed to assess vaccination coverage (VC) in 17-year-old French young adults (YAs) participating in one mandatory Day of Defence and Citizenship (DDC). Between June 2010 and May 2011, YAs participating in 43 randomly selected mandatory sessions of the DDC programme in Poitou-Charentes (France) were asked to provide their personal vaccination record. Tetanus, diphtheria, polio, hepatitis B, Haemophilus influenzae b, pertussis, measles, mumps and rubella vaccination status were assessed at ages 2, 6, 13 and 17 years. Of 2610 participants, 2111 (81%) supplied documents for evaluation. Of these, 1838 (87%, M:F sex ratio 0.96) were aged 17 years (9% of the global population of this age in the area). The assessment of the 17-year-olds demonstrated the following rates of complete vaccination: diphtheria-tetanus-polio 83%; measles, mumps and rubella 83%; pertussis 69%; H. influenzae b 61%; human papillomavirus 47%; and hepatitis B 40%. At age 6 years, only 46% had received two doses of the vaccine against measles. The YAs were not aware of their status but were in favour of vaccination. VC in YAs is insufficient, particularly for hepatitis B, pertussis and measles. Combined vaccines and the simplification of vaccination schedules should improve VC. Preventive messages should focus on YAs. PMID- 26159150 TI - Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages. AB - BACKGROUND/AIM: Sodium 9-acetoxyltanshinone IIA sulfonate (ZY-1A4), a novel compound derived from sodium 9-hydroxyltanshinone IIA sulfonate, was synthesized with potential biological activities. This study aimed to explore the effects of ZY-1A4 on lipopolysaccharide (LPS)-triggered inflammatory response and the underlying mechanisms. METHODS: Activation of RAW264.7 macrophages was induced by LPS. The effects of ZY-1A4 on inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) generation, nuclear factor-kappaB (NF-kappaB) activation, heme oxygenase-1 (HO-1) expression, and nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway were evaluated to elucidate its underlying mechanisms on inflammatory responses. RESULTS: ZY-1A4 concentration-dependently reduced iNOS expression and NO production, and inhibited c-Jun-N-terminal kinase 1/2 (JNK1/2) phosphorylation and NF-kappaB activation in LPS-stimulated macrophages. In addition, ZY-1A4 concentration- and time-dependently induced HO-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of Nrf2, while the effect of ZY-1A4 was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Intriguingly, pharmacological inactivation of HO-1 with zinc protoporphyrin IX reversed anti inflammatory effect of ZY- 1A4, but the anti-inflammatory effect of ZY-1A4 was largely mimicked by HO-1 by-products carbon monoxide and bilirubin. Furthermore, the inhibitory effect of ZY-1A4 on LPS-induced iNOS expression and NO release was abolished by HO-1 siRNA or LY294002. CONCLUSION: Our results demonstrated that ZY 1A4 suppressed LPS-induced iNOS expression and NO generation via modulation of NF kappaB activation and HO-1 expression. This new finding might shed light to the prevention and therapy of cardiovascular diseases. PMID- 26159151 TI - A label-free fluorescent molecular beacon based on DNA-Ag nanoclusters for the construction of versatile Biosensors. AB - In this paper, we developed a simple, low-cost and sensitive DNA sequences detection biosensor based on a label-free molecular beacon (MB) whose DNA hairpin structure terminal has a guanine-rich sequence that can enhance fluorescence of silver nanoclusters (Ag NCs). Without hybridization between hairpin probe and target DNA, the Ag NCs presented bright fluorescence for the proximity of guanine rich sequences (GRSs). After binding with target DNA, the hairpin shape was destroyed which results in a decrease of the Ag NCs fluorescence intensity. With this biosensor, we detected three disease-related genes that were the human immunodeficiency virus (HIV) gene, hepatitis B virus (HBV) gene and human T lymphotropic virus type I (HTLV-I) gene. The detection limits based on S/N of 3 were 4.4 nM, 6.8 nM and 8.5 nM for HIV gene, HBV gene and HTLV-I gene, respectively. Our sensor was also of high selectivity and could distinguish even one nucleotide mismatched target. PMID- 26159152 TI - Gold nanoparticles-decorated graphene field-effect transistor biosensor for femtomolar MicroRNA detection. AB - Early detection is proven to be the best chance for successful cancer treatment. MiRNAs, as ideal biomarkers, can identify cancer in the early stage. Therefore, development of highly sensitive and selective detection methods for miRNA is still anticipated. Here we report on a gold nanoparticles (AuNPs)-decorated graphene field-effect transistor (FET) biosensor for highly sensitive, selective and label-free detection of miRNA. The AuNPs-decorated graphene FET biosensor was fabricated by drop-casting the reduced graphene oxide (R-GO) suspension onto the sensor surface, and subsequently decorating AuNPs onto the surface of R-GO. After peptide nucleic acid (PNA) probe was immobilized on the AuNPs surface, miRNA detection was carried out via PNA-miRNA hybridization. It was found that the developed FET biosensor was able to achieve a detection limit as low as 10 fM. In addition, the biosensor enabled an accurate distinction of complementary miRNA from one-base mismatched miRNA and noncomplementary miRNA. What's more, this highly sensitive and selective assay was also applied to the detection of miRNA in serum samples, making it a potential method for diagnosis of gene-related diseases. PMID- 26159153 TI - SPR-DNA array for detection of methicillin-resistant Staphylococcus aureus (MRSA) in combination with loop-mediated isothermal amplification. AB - In this study, we evaluated surface plasmon resonance imaging (SPR imaging) as a DNA biosensor for the detection of methicillin-resistant Staphylococcus aureus (MRSA) which is one of the most common causes of nosocomial infections. The DNA sample were collected from clinical specimens, including sputum and blood hemoculture were undergone LAMP amplification for 0.18 kbp and 0.23 kbp DNA fragments of femB and mecA genes, respectively. The self-assembled monolayer surface (SAMs) was used for immobilized streptavidin-biotinylated probes on the sensor surface for the detection of LAMP amplicons from MRSA. Both LAMP amplicons were simultaneously hybridized with ssDNA probes immobilized onto a bio functionalized surface to detect specific targets in the multiplex DNA array platform. In addition, the sensor surface could be regenerated allowing at least five cycles of use with a shortened assay time. The detection limit of LAMP-SPR sensing was 10 copies/ul and LAMP-SPR sensing system showed a good selectivity toward the MRSA. PMID- 26159154 TI - A nanoplasmonic biosensor for label-free multiplex detection of cancer biomarkers. AB - The development of highly sensitive, selective and multiplex sensors has become an important challenge for disease diagnosis. In this study, we describe a multiplex biosensor for the detection of cancer biomarkers based on unique plasmon response of single gold nanoparticles (AuNPs) and antibody-antigen binding activity. To demonstrate the ability of the plasmon biosensor to detect and quantify cancer biomarkers: a panel of biomarkers, including alpha fetoprotein (AFP), carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) was used as a model analyte for multiple detection. A novel and sensitive multiplex biosensor was developed by immobilizing plasmonic nanoparticles in a site-specific manner and functionalized with monoclonal antibodies that recognize the target protein on hydrophilic-hydrophobic patterned glass slide. The proposed multi-analyte biosensor exhibited outstanding selectivity and sensitivity. The limit of detection was determined to be 91 fM, 94 fM and 10 fM for AFP, CEA and PSA from patient-mimicked serum, respectively. Finally, using this sensing strategy, this platform presents an excellent approach for versatile molecular diagnostics in both research and clinical medical fields. PMID- 26159155 TI - Novel phenol biosensor based on laccase immobilized on reduced graphene oxide supported palladium-copper alloyed nanocages. AB - Developing new nanomaterials is of key importance to improve the analytical performances of electrochemical biosensors. In this work, palladium-copper alloyed nanocages supported on reduced graphene oxide (RGO-PdCu NCs) were facilely prepared by a simple one-pot solvothermal method. A novel phenol biosensor based on laccase has been constructed for rapid detection of catachol, using RGO-PdCu NCs as electrode material. The as-developed phenol biosensor greatly enhanced the electrochemical signals for catechol. Under the optimal conditions, the biosensor has two linear ranges from 0.005 to 1.155 mM and 1.655 to 5.155 mM for catachol detection at 0.6 V, the sensitivity of 12.65 uA mM(-1) and 5.51 uA mM(-1), respectively. This biosensor showed high selectivity, low detection limit, good reproducibility, and high anti-interference ability. PMID- 26159156 TI - Green in-situ synthesized silver nanoparticles embedded in bacterial cellulose nanopaper as a bionanocomposite plasmonic sensor. AB - Herein, we introduce a new strategy for green, in-situ generation of silver nanoparticles using flexible and transparent bacterial cellulose nanopapers. In this method, adsorbed silver ions on bacterial cellulose nanopaper are reduced by the hydroxyl groups of cellulose nanofibers, acting as the reducing agent producing a bionanocomposite "embedded silver nanoparticles in transparent nanopaper" (ESNPs). The fabricated ESNPs were investigated and characterized by field emission scanning electron microscopy (FE-SEM), UV-visible spectroscopy (UV vis), Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and energy-dispersive X-ray spectroscopy (EDX). The important parameters affecting the ESNPs were optimized during the fabrication of specimens. The resulting ESNPs were used as a novel and sensitive probe for the optical sensing of cyanide ion (CN(-)) and 2-mercaptobenzothiazole (MBT) in water samples with satisfactory results. The change in surface plasmon resonance absorption intensity of ESNPs was linearly proportional to the concentration in the range of 0.2-2.5 ug mL(-1) and 2-110 ug mL(-1) with a detection limit of 0.012 ug mL(-1) and 1.37 ug mL(-1) for CN(-) and MBT, respectively. PMID- 26159157 TI - Massive gastric polyposis associated with a germline SMAD4 gene mutation. AB - Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. Polyps are most common in the colorectum (98% of patients) and the stomach (14%). Causative mutations for JPS have been identified in two genes to date, SMAD4 and BMPR1A. SMAD4 mutations are associated with a higher incidence of gastric polyposis. In this case report, we describe two patients with massive gastric polyposis associated with a SMAD4 mutation. Both presented with anaemia and both had colonic polyps. Initial endoscopic findings revealed giant rugal folds suggestive of Menetrier disease. However, as other possible gastropathies could not be differentiated on the basis of histology, a definitive diagnosis of JPS required additional mutation analysis. In patients with polyposis predominant in or limited to the stomach, establishing a diagnosis based solely on the pathological features of polyps can be challenging due to difficulties in differentiating JPS from other hypertrophic gastropathies. Mutation analysis should be considered early in the diagnostic process in cases of suspected juvenile polyposis, thus facilitating rapid diagnosis and adequate follow-up. PMID- 26159158 TI - The role of motor memory in action selection and procedural learning: insights from children with typical and atypical development. AB - Motor memory is the process by which humans can adopt both persistent and flexible motor behaviours. Persistence and flexibility can be assessed through the examination of the cooperation/competition between new and old motor routines in the motor memory repertoire. Two paradigms seem to be particularly relevant to examine this competition/cooperation. First, a manual search task for hidden objects, namely the C-not-B task, which allows examining how a motor routine may influence the selection of action in toddlers. The second paradigm is procedural learning, and more precisely the consolidation stage, which allows assessing how a previously learnt motor routine becomes resistant to subsequent programming or learning of a new - competitive - motor routine. The present article defends the idea that results of both paradigms give precious information to understand the evolution of motor routines in healthy children. Moreover, these findings echo some clinical observations in developmental neuropsychology, particularly in children with Developmental Coordination Disorder. Such studies suggest that the level of equilibrium between persistence and flexibility of motor routines is an index of the maturity of the motor system. PMID- 26159159 TI - Incidence of second primary cancers in North Portugal-a population-based study. AB - PURPOSE: Longitudinal studies are needed to characterise the burden of second primary malignancies among cancer survivors. Therefore, we quantified the incidence rate and cumulative incidence of second primary cancers (SPC) and standardised incidence ratios (SIR) in a population-based cohort of subjects diagnosed with a first primary cancer (FPC). METHODS: We evaluated a cohort of cancer patients from the Portuguese North Region Cancer Registry (RORENO), with the first diagnosis in 2000-2003 (n = 39451), to estimate the incidence rate and cumulative incidence of SPC and standardised incidence ratios (SIR), for different periods of follow-up, up to 5 years; SPC were defined according to the International Association of Cancer Registries and the International Agency for Research on Cancer guidelines. RESULTS: The incidence rate of SPC was more than 5 fold higher in the first 2 months of follow-up than in the period between 2 months and 5 years (metachronous SPC), across which the incidence rates were relatively stable. Cancer survivors had an overall higher incidence rate of cancer than the general population (SIR = 1.31 (95 % confidence interval (CI), 1.25-1.38)), although that difference faded when only metachronous SPC were considered (SIR = 1.02 (95 % CI, 0.96-1.08)). Cancer incidence rates were higher among female lung FPC survivors and lower in prostate FPC cancer survivors than in the general population. The 5-year cumulative risk of developing a metachronous SPC was 3.0 % and reached nearly 5.0 % among patients with FPC associated with lower risk of death. CONCLUSIONS: Cancer survivors had higher incident rates of cancer that the general population, especially due to diagnoses in the first months following the FPC. Nevertheless, after this period SPC remain frequent events among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: SPC constitute an important dimension of the burden of cancer survivorship, and this needs to be taken into account when defining strategies for surveillance, prevention and counselling. PMID- 26159161 TI - Cranberry anthocyanin extract prolongs lifespan of fruit flies. AB - Cranberry is an excellent source of dietary antioxidants. The present study investigated the effect of cranberry anthocyanin (CrA) extract on the lifespan of fruit flies with focus on its interaction with aging-related genes including superoxide dismutase (SOD), catalase (CAT), methuselah (MTH), insulin receptor (InR), target of rapamycin (TOR), hemipterus (Hep), and phosphoenolpyruvate carboxykinase (PEPCK). Results showed that diet containing 20mg/mL CrA could significantly prolong the mean lifespan of fruit flies by 10% compared with the control diet. This was accompanied by up-regulation of SOD1 and down-regulation of MTH, InR, TOR and PEPCK. The stress resistance test demonstrated that CrA could reduce the mortality rate induced by H2O2 but not by paraquat. It was therefore concluded that the lifespan-prolonging activity of CrA was most likely mediated by modulating the genes of SOD1, MTH, InR, TOR and PEPCK. PMID- 26159160 TI - Dismantling the present and future threats of testicular cancer: a grounded theory of positive and negative adjustment trajectories. AB - PURPOSE: Testicular cancer commonly affects men in the prime of their lives. While survival rates are excellent, little previous research has examined men's experiences of adjustment to survivorship. We aimed to explore this issue in younger testicular cancer survivors. METHODS: In-depth qualitative interviews were conducted with testicular cancer survivors over two time points approximately 6 months apart in the year following treatment completion. Interviews were analysed using a grounded theory approach. RESULTS: The sample included 18 testicular cancer survivors between 22 and 44 years (mean age 34). A grounded theory was developed, which explained the process of positive adjustment over the first year following the treatment completion in terms of men's ability to dismantle the present and future threats of cancer, involving the key transitions of gaining a sense of perspective and striving to get on with life and restore normality. These were facilitated by six key processes. The processes that explained a negative adjustment trajectory are also presented. CONCLUSIONS: These findings contribute to the understanding of the psychosocial impact of testicular cancer on younger men's lives and have implications for the provision of support to testicular cancer survivors. Further investigation into the feasibility of one-on-one peer support interventions is warranted, as well as informal support that respects men's desire for independence. IMPLICATIONS FOR CANCER SURVIVORS: Understanding the processes involved in adjustment highlights ways in which health professionals can offer support to those struggling to adjust through challenging illness beliefs, encouraging emotional disclosure and facilitating peer mentoring. PMID- 26159162 TI - Sex differences with aging in the fatigability of dynamic contractions. AB - This study determined the sex difference with aging in fatigability of the elbow flexor muscles during a dynamic fatiguing task, and explored the associated mechanisms. We compared fatigability of the elbow flexor muscles in 18 young (20.2 +/- 1 years: 9 men) and 36 old adults (73.5 +/- 1 years: 16 men) during and in recovery from repeated dynamic contractions (~60 degrees /s) with a load equivalent to 20% of maximal voluntary isometric contraction (MVIC) torque until failure. Transcranial magnetic stimulation (TMS) was used to assess supraspinal fatigue (an increase in the superimposed twitch, SIT) and the peak rate of muscle relaxation. Time to failure was briefer for the men than the women (6.1 +/- 2.1 vs. 9.7 +/- 5.5 min, respectively; P=0.02) with no difference between young and old adults (7.2 +/- 2.9 vs. 8.4 +/- 5.2 min, respectively, P=0.45) and no interaction (P>0.05). The relative decline in peak relaxation rate with fatigability was similar for young and old adults (P=0.11), but greater for men than women (P=0.046). Supraspinal fatigue increased for all groups and was associated with the time to failure (P<0.05). Regression analysis however, indicated that the time to failure was best predicted by the peak relaxation rate (baseline values and slowing with fatigability) (r(2)=0.55). Rate-limiting contractile mechanisms (e.g. excitation-contraction coupling) were responsible for the increased fatigability of the elbow flexors of men compared with women for a dynamic fatiguing task of slow angular velocity, and this sex difference was maintained with aging. The age difference in fatigability for the dynamic task was diminished for both sexes relative to what is typically observed with isometric fatiguing contractions. PMID- 26159163 TI - Liver transplantation in acute on chronic liver failure: challenges and an algorithm for patient selection and management. AB - Acute on chronic liver failure is an entity distinct from acute liver failure and acute decompensation of chronic liver disease. Despite best medical therapy, it is associated with high short-term mortality due to infection and organ failure. Liver transplantation is a potentially curative treatment option that has been shown to have good outcomes in this setting. As there are no reliable ways of predicting which subset of patients will recover spontaneously, early transplantation before establishment of full blown sepsis or organ failure is expected to have favorable outcomes with an acceptable risk. This article reviews current literature on liver transplantation for acute on chronic liver failure, discusses challenges in patient selection, and proposes an algorithm for management. PMID- 26159164 TI - Plasma Derived From Human Umbilical Cord Blood Modulates Mitogen-Induced Proliferation of Mononuclear Cells Isolated From the Peripheral Blood of ALS Patients. AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the spinal cord and brain. This disease clinically manifests as gradual muscular weakness and atrophy leading to paralysis and death by respiratory failure. While multiple interdependent factors may contribute to the pathogenesis of ALS, increasing evidence shows the possible presence of autoimmune mechanisms that promote disease progression. The potential use of plasma derived from human umbilical cord blood (hUCB) as a therapeutic tool is currently in its infancy. The hUCB plasma is rich in cytokines and growth factors that are required for growth and survival of cells during hematopoiesis. In this study, we investigated the effects of hUCB plasma on the mitogen-induced proliferation of mononuclear cells (MNCs) isolated from the peripheral blood of ALS patients and apoptotic activity by detection of caspase 3/7 expression of the isolated MNCs in vitro. Three distinct responses to phytohemagglutinin (PHA) induced proliferation of MNCs were observed, which were independent of age, disease duration, and the ALS rating scale: Group I responded normally to PHA, Group II showed no response to PHA, while Group III showed a hyperactive response to PHA. hUCB plasma attenuated the hyperactive response (Group III) and potentiated the normal response in Group I ALS patients, but did not alter that of the nonresponders to PHA (Group II). The elevated activity of caspase 3/7 observed in the MNCs from ALS patients was significantly reduced by hUCB plasma treatment. Thus, study results showing different cell responses to mitogen suggest alteration in lymphocyte functionality in ALS patients that may be a sign of immune deficiency in the nonresponders and autoimmunity alterations in the hyperactive responders. The ability of hUCB plasma to modulate the mitogen cell response and reduce caspase activity suggests that the use of hUCB plasma alone, or with stem cells, may prove useful as a therapeutic in ALS patients. PMID- 26159165 TI - Optimal combination of feature selection and classification via local hyperplane based learning strategy. AB - BACKGROUND: Classifying cancers by gene selection is among the most important and challenging procedures in biomedicine. A major challenge is to design an effective method that eliminates irrelevant, redundant, or noisy genes from the classification, while retaining all of the highly discriminative genes. RESULTS: We propose a gene selection method, called local hyperplane-based discriminant analysis (LHDA). LHDA adopts two central ideas. First, it uses a local approximation rather than global measurement; second, it embeds a recently reported classification model, K-Local Hyperplane Distance Nearest Neighbor(HKNN) classifier, into its discriminator. Through classification accuracy-based iterations, LHDA obtains the feature weight vector and finally extracts the optimal feature subset. The performance of the proposed method is evaluated in extensive experiments on synthetic and real microarray benchmark datasets. Eight classical feature selection methods, four classification models and two popular embedded learning schemes, including k-nearest neighbor (KNN), hyperplane k nearest neighbor (HKNN), Support Vector Machine (SVM) and Random Forest are employed for comparisons. CONCLUSION: The proposed method yielded comparable to or superior performances to seven state-of-the-art models. The nice performance demonstrate the superiority of combining feature weighting with model learning into an unified framework to achieve the two tasks simultaneously. PMID- 26159166 TI - Fecal microbiota transplantation restores dysbiosis in patients with methicillin resistant Staphylococcus aureus enterocolitis. AB - BACKGROUND: Nosocomial Methicillin-resistant Staphylococcus aureus (MRSA) enteritis is rare but can be fatal unless it is detected at an early stage and treated effectively. Dysbiosis of the gut is one of the leading reasons of MRSA enteritis. Fecal microbiota transplantation (FMT) is a burgeoning treatment to rectify this imbalance. But the impact of FMT on MRSA enterocoitis is still unknown yet. METHODS: A total of 5 patients diagnosed as MRSA enteritis during the early postoperative period were given vancomycin 2 g/day for 3 days and FMT for three continuous days as a standard treatment. RESULT: There was a 100% clinical response rate that all the symptoms resulting from MRSA enterocolitis disappeared and MRSA in the feces eliminated clearly. The microbiota profile in feces of the patients also regained balance. CONCLUSION: FMT can be a preferential measure to restore the dysbiosis caused by MSRA enterocolitis. PMID- 26159167 TI - Treatment of cricopharyngeal dysfunction: a comparative pilot study. AB - BACKGROUND: Cricopharyngeal dysfunction is a narrowing at the level of the upper oesophageal sphincter caused by failed or incomplete sphincter opening as a result of lack of pharyngoesophageal coordination or reduction in the muscular compliance of the upper oesophageal sphincter. Oropharyngeal dysphagia is a typical symptom. Videomanometry allows direct comparison of pressure readings with dynamic anatomy during swallowing. METHODS: This is a prospective randomized pilot study that compares the effect of balloon dilatation and laser myotomy in cricopharyngeal dysfunction. We used videomanometry as an objective measure and the Swedish version of Sydney Swallowing Questionnaire as patient's self assessment at baseline and 1 and 6 months after treatment. RESULTS: The UES sagittal diameter increased from 5.6 mm pre-operatively to 8.4 mm 6 months post operatively with no differences between treatment groups. Preoperative mean Sydney Swallowing Questionnaire score was 770 and 6 months post-operative score 559, with no difference between the treatments in our cohort. CONCLUSION: Cricopharyngeal dysfunction treatment by either laser myotomy or balloon dilatation improved upper oesophageal sphincter opening during at least 6 months. TRIAL REGISTRATION: ISRCTN84905610, date: 081214. PMID- 26159168 TI - Genetic diversity of Plasmodium vivax in clinical isolates from Bangladesh. AB - BACKGROUND: Plasmodium vivax is the second most prevalent human malaria parasite in Bangladesh; however, there are no data of its genetic diversity. Several molecular markers are available where Pvcsp, Pvmsp 1 and Pvmsp 3alpha are most commonly used for P. vivax genotyping studies. The aim of the study was to investigate the population structure of P. vivax in Bangladesh. METHODS: A total of 102 P. vivax-positive blood samples were collected from different malaria endemic areas in Bangladesh and subsequently analysed for those three genotyping markers. Nested PCR was performed for diagnosis and genotyping analysis followed by PCR-RFLP to detect genetic diversity using Pvcsp, Pvmsp 1 and Pvmsp 3alpha markers. RESULTS: Analysis of Pvcsp showed that the VK210 repeat type was highly prevalent (64.7%, 66/102) compared to VK247 (35.3%, 36/102), although the prevalence of VK247 was higher than other Southeast Asian countries. Analysis of these three genes revealed a diverse, circulating population of P. vivax where a total of ten, 56 and 35 distinct genotypes were detected for Pvcsp, Pvmsp 1 and Pvmsp 3alpha, respectively. CONCLUSION: This genotyping observation of P. vivax is the first report from Bangladesh and will provide valuable information for establishing the genotyping methods and circulating genetic variants of these three markers available in Bangladesh. PMID- 26159170 TI - Corrigendum. AB - Roberto Da Cas, Anna Nigro, Salvatore Terrazzino, Grazia Sances, Michele Viana, Cristina Tassorelli, Giuseppe Nappi, Sarah Cargnin, Alessia Pisterna, Giuseppe Traversa and Armando A Genazzani. Triptan use in Italy: Insights from administrative databases. Cephalalgia 2015; 35: 619-626. DOI: 10.1177/0333102414550419. In the published version of this article, the author names and affiliations were represented as below: Roberto Da Cas,, Anna Nigro, Salvatore Terrazzino, Grazia Sances, Michele Viana, Cristina Tassorelli,Giuseppe Nappi, Sarah Cargnin, Alessia Pisterna, Giuseppe Traversa and Armando A Genazzani. National Centre for Epidemiology, Surveillance and Health Promotion, National Institute of Health, Italy S.C. Farmaceutica Territoriale, Italy Department of Pharmaceutical Sciences, "A. Avogadro" University, Italy Headache Science Center - C. Mondino National Neurological Institute, Italy However, the affiliations for Cristina Tassorelli should have been written correctly as follows: Cristina Tassorelli, Headache Science Center - C. Mondino National Neurological Institute, Italy Department of Brain and Behavioral Sciences, University of Pavia, Italy. The authors apologize for this mistake. PMID- 26159169 TI - Multifocal sclerosing angiomatoid nodular transformation of the spleen: a case report and review of literature. AB - Sclerosing angiomatoid nodular transformation (SANT) is a relatively new entity in the spleen, which usually presents in the form of single nodule. Only 5 multifocal SANT cases have been reported in English literature. The present case is the first report of a 38-years-old male patient with SANT in the form of multiple nodules, who has been cured via laparoscope. In comparison to solitary SANT, multifocal SANT occurs more likely in males than females and association with malignant neoplasm has not been described yet. Multifocal SANT as well as solitary SANT show some relationships with IgG4-related sclerosing disease. PMID- 26159171 TI - Experimental Investigation of Inter-Element Isolation in a Medical Array Transducer at Various Manufacturing Stages. AB - This work presents the experimental investigation of vibration maps of a linear array transducer with 192 piezoelements by means of a laser Doppler vibrometer at various manufacturing finishing steps in air and in water. Over the years, many researchers have investigated cross-coupling in fabricated prototypes but not in arrays at various manufacturing stages. Only the central element of the array was driven at its working frequency of 5 MHz. The experimental results showed that the contributions of cross-coupling depend on the elements of the acoustic stack: Lead Zirconate Titanate (PZT), kerf, filler, matching layer, and lens. The oscillation amplitudes spanned from (6 +/- 38%) nm to (110 +/- 40%) nm when the energized element was tested in air and from (6 +/- 57%) nm to (80 +/- 67%) nm when measurements were obtained under water. The best inter-element isolation of 22 dB was measured in air after cutting the kerfs, whereas the poorest isolation was -2 dB under water with an acoustic lens (complete acoustic stack). The vibration pattern in water showed a higher standard deviation on the displacement measurements than the one obtained in air, due to the influence of acousto-optic interactions. The amount increased to 30% in water, as estimated by a comparison with the measurements in air. This work describes a valuable method for manufacturers to investigate the correspondence between the manufacturing process and the quantitative evaluations of the resulting effects. PMID- 26159172 TI - Hospices still outperform hospitals on quality of care at end of life. PMID- 26159173 TI - Hidden Owners, Hidden Profits, and Poor Nursing Home Care: A Case Study. AB - The study examined the ownership transparency, financial accountability, and quality indicators of a regional for-profit nursing home chain in California, using a case study methodology to analyze data on the chain's ownership and management structure, financial data, staffing levels, deficiencies and complaints, and litigation. Secondary data were obtained from regulatory and cost reports and litigation cases. Qualitative descriptions of ownership and management were presented and quantitative analyses were conducted by comparing financial and quality indicators with other California for-profit chains, for profit non-chains, and nonprofit nursing home groups in 2011. The chain's complex, interlocking individual and corporate owners and property companies obscured its ownership structure and financial arrangements. Nursing and support services expenditures were lower than nonprofits and administrative costs were higher than for-profit non-chains. The chain's nurse staffing was lower than expected staffing levels; its deficiencies and citations were higher than in nonprofits; and a number of lawsuits resulted in bankruptcy. Profits were hidden in the chain's management fees, lease agreements, interest payments to owners, and purchases from related-party companies. Greater ownership transparency and financial accountability requirements are needed to ensure regulatory oversight and quality of care. PMID- 26159174 TI - Distributional Orientation and Health Outcomes in OECD Countries. AB - This study uses data from the Organisation for Economic Co-operation and Development countries over the 2008-2010 period to construct indicators of "pro primary" and "pro-secondary" distributions. The former is concerned with the original distribution of income through the market, whereas the latter is concerned with the redistribution efforts of the government. The study ranks these countries along these dimensions to create a distributional orientation map for such countries. It finds that the Scandinavian countries occupy the top rankings in terms of equity in pro-primary distribution, followed by countries with a Bismarckian welfare state regime. The Scandinavian countries also rank very high on equity in pro-secondary distribution, along with some of the top ranking Bismarckian countries. More significantly, the study finds that the countries' health outcomes are associated more strongly with the pro-primary distributional stance than with the pro-secondary distributional stance. A key policy implication is that to achieve better and more equitable health, it is more effective to design a level playing field for market participants in the first place, than to try to mend inequities after the fact through remedial social policy. PMID- 26159175 TI - Augmented Stat5 Signaling Bypasses Multiple Impediments to Lactogen-Mediated Proliferation in Human beta-Cells. AB - Pregnancy in rodents is associated with a two- to threefold increase in beta-cell mass, which is attributable to large increases in beta-cell proliferation, complimented by increases in beta-cell size, survival, and function and mediated mainly by the lactogenic hormones prolactin (PRL) and placental lactogens. In humans, however, beta-cell mass does not increase as dramatically during pregnancy, and PRL fails to activate proliferation in human islets in vitro. To determine why, we explored the human PRL-prolactin receptor (hPRLR)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5)-cyclin-cdk signaling cascade in human beta-cells. Surprisingly, adult human beta-cells express little or no PRLR. As expected, restoration of the hPRLR in human beta cells rescued JAK2-STAT5 signaling in response to PRL. However, rescuing hPRLR STAT5 signaling nevertheless failed to confer proliferative ability on adult human beta-cells in response to PRL. Surprisingly, mouse (but not human) Stat5a overexpression led to upregulation of cyclins D1-3 and cdk4, as well as their nuclear translocation, all of which are associated with beta-cell cycle entry. Collectively, the findings show that human beta-cells fail to proliferate in response to PRL for multiple reasons, one of which is a paucity of functional PRL receptors, and that murine Stat5 overexpression is able to bypass these impediments. PMID- 26159176 TI - A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly. AB - Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) are associated with pancreatic beta-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2alpha phosphorylation [CReP]) encoding the regulatory subunit of an eIF2alpha-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2alpha dephosphorylation and results in beta-cell apoptosis. Our findings support the concept that dysregulated eIF2alpha phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to beta-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities. PMID- 26159178 TI - Beneficial Role of Copper in the Enhancement of Durability of Ordered Intermetallic PtFeCu Catalyst for Electrocatalytic Oxygen Reduction. AB - Design of Pt alloy catalysts with enhanced activity and durability is a key challenge for polymer electrolyte membrane fuel cells. In the present work, we compare the durability of the ordered intermetallic face-centered tetragonal (fct) PtFeCu catalyst for the oxygen reduction reaction (ORR) relative to its counterpart bimetallic catalysts, i.e., the ordered intermetallic fct-PtFe catalyst and the commercial catalyst from Tanaka Kikinzoku Kogyo, TKK-PtC. Although both fct catalysts initially exhibited an ordered structure and mass activity approximately 2.5 times higher than that of TKK-Pt/C, the presence of Cu at the ordered intermetallic fct-PtFeCu catalyst led to a significant enhancement in durability compared to that of the ordered intermetallic fct-PtFe catalyst. The ordered intermetallic fct-PtFeCu catalyst retained more than 70% of its mass activity and electrochemically active surface area (ECSA) over 10 000 durability cycles carried out at 60 degrees C. In contrast, the ordered intermetallic fct PtFe catalyst maintained only about 40% of its activity. The temperature of the durability experiment is also shown to be important: the catalyst was more severely degraded at 60 degrees C than at room temperature. To obtain insight into the observed enhancement in durability of fct-PtFeCu catalyst, a postmortem analysis of the ordered intermetallic fct-PtFeCu catalyst was carried out using scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDX) line scan. The STEM-EDX line scans of the ordered intermetallic fct PtFeCu catalyst over 10 000 durability cycles showed a smaller degree of Fe and Cu dissolution from the catalyst. Conversely, large dissolution of Fe was identified in the ordered intermetallic fct-PtFe catalyst, indicating a lesser retention of Fe that causes the destruction of ordered structure and gives rise to poor durability. The enhancement in the durability of the ordered intermetallic fct-PtFeCu catalyst is ascribed to the synergistic effects of Cu presence and the ordered structure of catalyst. PMID- 26159177 TI - Early and Late G1/S Cyclins and Cdks Act Complementarily to Enhance Authentic Human beta-Cell Proliferation and Expansion. AB - beta-Cell regeneration is a key goal of diabetes research. Progression through the cell cycle is associated with retinoblastoma protein (pRb) inactivation via sequential phosphorylation by the "early" cyclins and cyclin-dependent kinases (cdks) (d-cyclins cdk4/6) and the "late" cyclins and cdks (cyclin A/E and cdk1/2). In beta-cells, activation of either early or late G1/S cyclins and/or cdks is an efficient approach to induce cycle entry, but it is unknown whether the combined expression of early and late cyclins and cdks might have synergistic or additive effects. Thus, we explored whether a combination of both early and late cyclins and cdks might more effectively drive human beta-cell cell cycle entry than either group alone. We also sought to determine whether authentic replication with the expansion of adult human beta-cells could be demonstrated. Late cyclins and cdks do not traffic in response to the induction of replication by early cyclins and cdks in human beta-cells but are capable of nuclear translocation when overexpressed. Early plus late cyclins and cdks, acting via pRb phosphorylation on distinct residues, complementarily induce greater proliferation in human beta-cells than either group alone. Importantly, the combination of early and late cyclins and cdks clearly increased human beta-cell numbers in vitro. These findings provide additional insight into human beta-cell expansion. They also provide a novel tool for assessing beta-cell expansion in vitro. PMID- 26159179 TI - Online Alcohol Assessment and Feedback for Hazardous and Harmful Drinkers: Findings From the AMADEUS-2 Randomized Controlled Trial of Routine Practice in Swedish Universities. AB - BACKGROUND: Previous research on the effectiveness of online alcohol interventions for college students has shown mixed results. Small benefits have been found in some studies and because online interventions are inexpensive and possible to implement on a large scale, there is a need for further study. OBJECTIVE: This study evaluated the effectiveness of national provision of a brief online alcohol intervention for students in Sweden. METHODS: Risky drinkers at 9 colleges and universities in Sweden were invited by mail and identified using a single screening question. These students (N=1605) gave consent and were randomized into a 2-arm parallel group randomized controlled trial consisting of immediate or delayed access to a fully automated online assessment and intervention with personalized feedback. RESULTS: After 2 months, there was no strong evidence of effectiveness with no statistically significant differences in the planned analyses, although there were some indication of possible benefit in sensitivity analyses suggesting an intervention effect of a 10% reduction (95% CI -30% to 10%) in total weekly alcohol consumption. Also, differences in effect sizes between universities were seen with participants from a major university (n=365) reducing their weekly alcohol consumption by 14% (95% CI -23% to -4%). However, lower recruitment than planned and differential attrition in the intervention and control group (49% vs 68%) complicated interpretation of the outcome data. CONCLUSIONS: Any effects of current national provision are likely to be small and further research and development work is needed to enhance effectiveness. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 02335307; http://www.isrctn.com/ISRCTN02335307 (Archived by WebCite at http://www.webcitation.org/6ZdPUh0R4). PMID- 26159181 TI - Novel nanostructured lipid carrier-based inserts for controlled ocular drug delivery: evaluation of corneal bioavailability and treatment efficacy in bacterial keratitis. AB - OBJECTIVES: The aim of the present study was to develop novel ofloxacin (OFX) loaded nanostructured lipid carrier (NLC)-based inserts for ocular application for treatment of bacterial keratitis. METHODS: NLC loaded with 0.3% OFX was prepared by means of high shear homogenization and 0.75% chitosan oligosaccharide lactate (COL) was added. Glycerin or PEG 400 at the range of 1 - 15% was added to NLCs as plasticizers and inserts were developed by solvent casting evaporation. Characterization, in vitro release, microbiological, ex vivo and in vivo studies were performed. RESULTS: The inserts developed with the addition of glycerin (Ins3OFX) was found as optimal. The kinetic studies revealed that the release of Ins3OFX was a combination of diffusion and swelling. Ins3OFX was more bioadhesive in texture profile analysis studies. In the in vivo studies performed with rabbits, the pre-ocular retention time was enhanced up to 24 h and Cmax was increased almost six times in comparison with commercial. The rabbits were infected with Staphylococcus aureus and keratitis was confirmed. This group was treated with Ins3OFX and they recovered in 7 days with no significant sign of conjunctival redness and corneal opacity. CONCLUSION: NLC-based inserts developed with COL and glycerin may be offered as appropriate vehicles for ocular delivery. PMID- 26159183 TI - Smad Anchor for Receptor Activation Regulates High Glucose-Induced EMT via Modulation of Smad2 and Smad3 Activities in Renal Tubular Epithelial Cells. AB - BACKGROUND: SARA is an essential adaptor protein in TGF-beta1 signaling and it is also involved in the process of Epithelial-mesenchymal transition (EMT) and fibrosis. Our aim was to investigate the effect of SARA on high glucose (HG) induced EMT and extracellular matrix (ECM) synthesis in renal tubular epithelial cells. METHODS: The cells were transfected with the following plasmids: wild-type SARA (SARA-WT), SARA-dSBD (SARA with Smad binding domain deletion) and then subjected to HG ambience (30 mM). The expression levels were assessed by Western blot, real-time PCR and immunofluorescence. RESULTS: HG-induced EMT phenotype with increased expression of ECM protein in HK-2 cells. This was associated with the decreased expression of SARA and Smad2. In comparison with the HG group, overexpression of SARA in HK-2 cells, a relatively high upregulation of ZO-1 expression was seen, while that of Vimentin, fibronectin and collagen I was decreased. The Smad2 protein expression was increased in HK-2 cells after transfection with SARA (WT) plasmid. Interestingly, the overexpression of SARA prolonged the activity period of Smad2 and shortened that of Smad3, which seemed consistent with the change of EMT phenotype and ECM changes in HK-2 cell induced by HG. CONCLUSIONS: SARA regulates HG-induced EMT and ECM excretion via modulation of the activation of Smad2 and Smad3 in renal tubular epithelial cells. In view of these findings, it is conceivable that SARA may serve as a potential novel target in pre-EMT states for the amelioration renal fibrosis seen in chronic kidney diseases. PMID- 26159182 TI - Effects of Long-Term Treatment with Estradiol and Estrogen Receptor Subtype Agonists on Serotonergic Function in Ovariectomized Rats. AB - Acute estradiol treatment was reported to slow the clearance of serotonin via activation of estrogen receptors (ER)beta and/or GPR30 and to block the ability of a selective serotonin reuptake inhibitor (SSRI) to slow serotonin clearance via activation of ERalpha. In this study, the behavioral consequences of longer term treatments with estradiol or ER subtype-selective agonists and/or an SSRI were examined in the forced swim test (FST). Ovariectomized rats were administered the following for 2 weeks: estradiol, ERbeta agonist (diarylpropionitrile, DPN), GPR30 agonist (G1), ERalpha agonist (PPT), and/or the SSRI sertraline. Similar to sertraline, longer-term treatment with estradiol, DPN or G1 induced an antidepressant-like effect. By contrast, PPT did not, even though it blocked the antidepressant-like effect of sertraline. Uterus weights, used as a peripheral measure of estrogenic activity, were increased by estradiol and PPT but not DPN or G1 treatment. A second part of this study investigated, using Western blot analyses in homogenates from hippocampus, whether these behavioral effects are accompanied by changes in the activation of specific signaling pathways and/or TrkB. Estradiol and G1 increased phosphorylation of Akt, ERK and TrkB. These effects were similar to those obtained after treatment with sertraline. Treatment with DPN increased phosphorylation of ERK and TrkB, but it did not alter that of Akt. Treatment with PPT increased phosphorylation of Akt and ERK without altering that of TrkB. In conclusion, activation of at least TrkB and possibly ERK may be involved in the antidepressant-like effect of estradiol, ERbeta and GPR30 agonists whereas Akt activation may not be necessary. PMID- 26159184 TI - Diesel Exhaust Particles Induce Impairment of Vascular and Cardiac Homeostasis in Mice: Ameliorative Effect of Emodin. AB - BACKGROUND/AIM: There is strong epidemiological and clinical evidence that components of the cardiovascular system are adversely affected by particulate air pollutants through the generation of inflammation and oxidative stress. Emodin (1,3,8-trihydroxy-6- methylanthraquinone), which is commonly found in the roots of rhubarb plant, has strong antioxidant and anti-inflammatory effects. However, its possible protective effect on the cardiovascular effect of particulate air pollutants has never been reported before. METHODS: We tested, in Tuck-Ordinary mice, the possible ameliorative effect of emodin on the acute (24h) cardiovascular effects of diesel exhaust particles (DEP, 1 mg/kg) or saline (control). Emodin (4 mg/kg) was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty four h following DEP exposure, several cardiovascular endpoints were assessed. RESULTS: Emodin significantly prevented the increase of leukocyte (n=8, P<0.001) and erythrocyte (n=8, P<0.01) numbers caused by DEP. Likewise, emodin abrogated DEP-induced increase of heart tissue levels of interleukin 1beta (n=8, P<0.01) and tumour necrosis factor alpha (n=8, P<0.05), and significantly mitigated the change of the activities of antioxidant enzymes superoxide dismutase (n=8, P<0.001) and glutathione reductase (n=8, P<0.05). Emodin abolished the in vivo prothrombotic effect of DEP in pial arterioles (n=6, P<0.01) and venules (n=6, P<0.001). Similarly, emodin prevented platelet aggregation in vitro in whole blood (n=4-5, P<0.01), and the shortening of activated partial thromboplastin time (n=4, P<0.001) and prothrombin time (n=4, P<0.01) caused by DEP. CONCLUSION: We conclude that emodin treatment has consistently protected against DEP-induced impairment of vascular and cardiac homeostasis in mice. Our study provides experimental evidence that the use of functional food such as emodin, pending further studies, can be considered a useful agent and may have the potential to protect or mitigate the cardiovascular detrimental effects observed in people living in cities with high concentrations of particulate air pollution. PMID- 26159185 TI - Optical sensing of phenylalanine in urine via extraction with magnetic molecularly imprinted poly(ethylene-co-vinyl alcohol) nanoparticles. AB - Incorporation of superparamagnetic nanoparticles into molecularly imprinted polymers (MIPs) is useful for both bioseparations and for concentration and sensing of biomedically relevant target molecules in physiological fluids, through the application of a magnetic field. In this study, we combined the separation and concentration of a target (phenylalanine) in urine, using magnetic molecularly imprinted polymeric composite nanoparticles, with optical sensing, to improve assay sensitivity. This target is important as a catecholamine precursor, and as an important amino acid constituent of proteins. Poly(ethylene-co-vinyl alcohol)s were imprinted with target molecules, and showed a high imprinting effectiveness (target binding compared with binding to non-imprinted polymer particles.) Fluorescence spectrophotometry was used to measure binding of the target, and also binding of possible interfering compounds. These measurements suggest that functional groups on phenylalanine dominate the selectivity of the synthesized MIPs. Finally, the composite nanoparticles were used to separate and sense the target molecule in urine by Raman scattering microscopy. PMID- 26159187 TI - An Acute Complication of Ventriculoperitoneal Shunt with Bladder Perforation and Extrusion through the Urethra in a Newborn: Case Report and Review of the Literature. AB - Ventriculoperitoneal shunt (VPS) surgery is a standard procedure for the management of hydrocephalus. Bladder perforation is an extremely rare complication of VPS surgery. Herein, we present for the first time an acute complication of VPS with bladder perforation and extrusion through the urethra in a newborn. We also reviewed the complication of VPS with bladder perforation as reported in the literature. PMID- 26159186 TI - Early Persistent Blood Eosinophilia in Necrotizing Enterocolitis Is a Predictor of Late Complications. AB - BACKGROUND: Eosinophils infiltrate intestinal tissue during necrotizing enterocolitis (NEC) and adult bowel diseases. We theorized that epithelial damage causes eosinophilic activation and recruitment at NEC onset. OBJECTIVE: We studied the relationship between persistent blood eosinophilia and medical or surgical complications during NEC. METHODS: NEC cases and controls at MU Children's Hospital (2008-2013) underwent review. A Likert scale measured NEC severity. We utilized an SPSS database for statistical analyses. RESULTS: Of 50 NEC cases, infants in group 1 (n = 15) had eosinophilia <2 days after onset and those in group 2 (n = 25) had NEC but no persistent eosinophilia. Group 3 (n = 46) consisted of controls, i.e. infants without NEC matched for birth weight and gestational age and group 4 (n = 4) of preterm infants with infection and <=5 days of eosinophilia. Hematologic assessment defined persistent eosinophilia as >=5% eosinophils for >=5 days after NEC onset. Absolute eosinophil counts were 2 times higher in group 1 than in group 2 (p = 0.002). The mean duration of eosinophilia was 8 days in group 1 versus 1 day in group 2 (p < 0.001). A Likert score of NEC severity was 3-fold higher in group 1 than in group 2 (p < 0.001). Compared to group 2, group 1 infants were 8 times more likely to have hepatic fibrosis or intestinal strictures. CONCLUSIONS: Early persistent blood eosinophilia is not currently a predictor of complications after the onset of NEC. This biomarker identifies immature infants at a high risk for adverse outcomes during NEC convalescence. PMID- 26159188 TI - Cognitive Improvement by Photic Stimulation in a Mouse Model of Alzheimer's Disease. AB - We previously reported that activity of the large conductance calcium-activated potassium (big-K, BK) channel is suppressed by intracellular Abeta in cortical pyramidal cells, and that this suppression was reversed by expression of the scaffold protein Homer1a in 3xTg Alzheimer's disease model mice. Homer1a is known to be expressed by physiological photic stimulation (PS) as well. The possibility thus arises that PS also reverses Abeta-induced suppression of BK channels, and thereby improves cognition in 3xTg mice. This possibility was tested here. Chronic application of 6-hour-long PS (frequency, 2 Hz; duty cycle, about 1/10; luminance, 300 lx) daily for 4 weeks improved contextual and tone-dependent fear memory in 3xTg mice and, to a lesser extent, Morris water maze performance as well. Hippocampal long-term potentiation was also enhanced after PS. BK channel activity in cingulate cortex pyramidal cells and lateral amygdalar principal cells, suppressed in 3xTg mice, were facilitated. In parallel, neuronal excitability, elevated in 3xTg mice, was recovered to the control level. Gene expression of BK channel, as well as that of the scaffold protein Homer1a, was found decreased in 3xTg mice and reversed by PS. It is known that Homer1a is an activity-dependently inducible immediate early gene product. Consistently, our previous findings showed that Homer1a induced by electrical stimulation facilitated BK channels. By using Homer1a knockouts, we showed that the present PS-induced BK channel facilitation is mediated by Homer1a expression. We thus propose that PS might be potentially useful as a non-invasive therapeutic measure against Alzheimer's disease. PMID- 26159190 TI - Amyloid-beta in the Cerebrospinal Fluid of APP Transgenic Mice Does not Show Prion-like Properties. AB - Early diagnosis of Alzheimer's disease (AD) is currently difficult and involves a complex approach including clinical assessment, neuroimaging, and measurement of amyloid-beta (Abeta) and tau levels in cerebrospinal fluid (CSF). A better mechanistic understanding is needed to develop more accurate and even presymptomatic diagnostic tools. It has been shown that Abeta derived from amyloid-containing brain tissue has prion-like properties: it induces misfolding and aggregation of Abeta when injected into human amyloid precursor protein (APP) transgenic mice. In contrast, Abeta in the CSF has been less studied, and it is not clear whether it also exhibits prion-like characteristics, which might provide a sensitive diagnostic tool. Therefore, we collected CSF from APP transgenic mice carrying the Swedish mutation (APP23 mice), and injected it intracerebrally into young mice from the same transgenic line. We found that CSF derived Abeta did not induce increased beta-amyloidosis, even after long incubation periods and additional concentration. This suggests that Abeta present in the CSF does not have the same prion-like properties as the Abeta species in the brain. PMID- 26159189 TI - Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer's Disease. AB - Alzheimer's disease (AD) is an aging-related multi-factorial disorder to which metabolic factors contribute at what has canonically been considered a centrally mediated process. Although the exact underlying mechanisms are still unknown, obesity is recognized as a risk factor for AD and the condition of insulin resistance seems to be the link between the two pathologies. Using mice with high fat diet (HFD) obesity we dissected the molecular mechanisms shared by the two disorders. Brains of HFD fed mice showed elevated levels of APP and Abeta40/Abeta42 together with BACE, GSK3beta and Tau proteins involved in APP processing and Abeta accumulation. Immunofluorescence, Thioflavin T staining experiments, confirmed increased Abeta generation, deposition in insoluble fraction and plaques formation in both the hippocampus and the cerebral cortex of HFD mice. Presence of Abeta40/Abeta42 in the insoluble fraction was also shown by ELISA assay. Brain insulin resistance was demonstrated by reduced presence of insulin receptor (IRs) and defects in Akt-Foxo3a insulin signaling. We found reduced levels of phospho-Akt and increased levels of Foxo3a in the nuclei of neurons where proapototic genes were activated. Dysregulation of different genes related to insulin resistance, especially those involved in inflammation and adipocytokines synthesis were analyzed by Profiler PCR array. Further, HFD induced oxidative stress, mitochondrial dysfunction and dynamics as demonstrated by expression of biomarkers involved in these processes. Here, we provide evidence that obesity and AD markers besides insulin resistance are associated with inflammation, adipokine dyshomeostasis, oxidative stress and mitochondrial dysfunction, all mechanisms leading to neurodegeneration. PMID- 26159191 TI - Screening of Early and Late Onset Alzheimer's Disease Genetic Risk Factors in a Cohort of Dementia Patients from Liguria, Italy. AB - Cohorts from a defined geographical area enable ad hoc genotype-phenotype correlation studies providing novel and unique insight into disease. We analysed genetic risk factors associated with early and late onset Alzheimer's disease (EOAD and LOAD) in a population from Liguria (northern Italy), as part of an ongoing longitudinal study. We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT, GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU, CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1, PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer's and non-Alzheimer's forms of dementias in all dementia cases might be warranted. The analysis of the LOAD risk factors revealed no association with AD or AD + MCI status after Bonferroni correction. Lack of association with APOE is supported by previous studies in the Italian population. Our data also evidenced: 1) a potentially protective haplotype at the PSEN2 locus; 2) a nominal association with the GWAS-risk allele A for rs3818361 in CR1 and; 3) a threefold prevalence of AD in the female population compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area. PMID- 26159192 TI - Mediterranean Diet and Risk of Dementia. AB - Dementia is a major global health challenge, as its burden on society will increase with population aging. Given the lack of effective pharmaceutical treatment for common types of dementia including Alzheimer's disease and vascular dementia, research interest in lifestyle modifications that could prevent, postpone the clinical syndrome or decelerate progression of dementia is growing. Among the various dietary patterns that were tested for their effects on cognition, the traditional Mediterranean diet (MeDi) has shown promising results. This review aims to summarize the epidemiological evidence on the effects of MeDi on the prevention of dementia, presenting data from cross-sectional as well as longitudinal observational studies conducted both in Mediterranean and non Mediterranean countries. These findings have been also reproduced in the context of one recent randomized-controlled clinical trial. Postulated mechanisms of action that may account for the potential protective effect of MeDi on cognitive impairment will be briefly discussed. Despite the fact that the link between MeDi and cognitive decline has been only explored for less than a decade, data on efficacy is rapidly increasing and allows optimism that MeDi could emerge as an alternative prophylactic treatment for dementia. PMID- 26159194 TI - Emotion and Destination Memory in Alzheimer's Disease. AB - Research shows beneficial effect of emotion on self-related information in patients with Alzheimer's Disease (AD). Our paper investigates whether emotion improves destination memory (e.g., did I tell you about the manuscript?), which is thought to be self-related (e.g., did I tell you about the manuscript?). To this aim, twenty-seven AD patients and thirty healthy older adults told 24 neutral facts to eight neutral faces, eight positive faces, and eight negative faces. On a subsequent recognition task, participants had to decide whether they had previously told a given fact to a given face or not. Data revealed no emotional effect on destination memory in AD patients. However, in healthy older adults, better destination memory was observed for negative faces than for positive faces, and the latter memory was better than for neutral faces. The absence of emotional effect on destination memory in AD is interpreted in terms of substantial decline in this memory in the disease. PMID- 26159193 TI - Increased Acetylation of Histone H4 at Lysine 12 (H4K12) in Monocytes of Transgenic Alzheimer's Mice and in Human Patients. AB - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Abeta) plaque formation, tau pathology, neurodegeneration and inflammatory processes. Monocytes are involved in inflammation in AD and are recruited to the diseased brain. Recently it has been shown that aberrant epigenetic processes including acetylation are associated with the development of AD. The aim of the present study was to examine acetylation of histone H4 at lysine 12 (H4K12) in monocytes in two transgenic AD mouse models (the triple transgenic 3xTg and a model overexpressing amyloid precursor protein APP with the Swedish-Dutch-Iowa mutations), and to compare with monocytes isolated from human patients with mild cognitive impairment (MCI) and AD. METHODS: Mouse and human monocytes were selectively isolated with a positive (PluriSelect) respectively with a negative selection method (Miltenyi). Histones were extracted and acetylation of H4K12 was analyzed by a quantification fluorometric kit. Moreover, monocyte cytokine release was measured and cell death analyzed by FACS using incorporation of 7-AAD. RESULTS: Our data show a significant increase of monocytic H4K12 acetylation in both transgenic AD mouse models early during development of the plaque deposition in the brain. In line with these data we found significantly elevated acetylation of H4K12 in human patients with MCI but not in patients with AD. Further we observed that the monocytes of AD mice and of AD patients were significantly more vulnerable to cell damage (as seen by 7-AAD incorporation in FACS analysis) and displayed an enhanced release of pro-inflammatory cytokines (MIP2 and TNFalpha). CONCLUSION: Our findings indicate that epigenetic changes in peripheral monocytes are an early event in AD-pathology. Thus H4K12 acetylation may be considered as a novel biomarker for early changes in AD development. PMID- 26159195 TI - Mitochondrial Deficits Accompany Cognitive Decline Following Single Bilateral Intracerebroventricular Streptozotocin. AB - BACKGROUND: Bilateral intracerebroventricular (ICV) administration of streptozotocin (STZ) causes Alzheimer's disease (AD)-type neurodegeneration in rats. The model is increasingly used for investigating pathology and therapeutic strategies for AD. OBJECTIVE: The present study investigated cognitive abilities in rats infused with STZ-ICV in relation to hippocampal and cortical mitochondrial functions during a period of 60 days. METHODS: Cognitive functions were assayed in rats employing various mazes. Mitochondrial state-3-respiration, complex-I activity and dynamin related protein-1 (DRP-1) expression were measured respectively by oxygraph, spectrophotometry and immunoblot assay. Amyloidosis was investigated employing Congo red staining. RESULTS: One-time ICV-STZ infused animals exhibited body-weight loss and impaired cognitive ability from 14(th) day post-infusion. A significant loss of mitochondrial electron transport chain complex-I activity in the hippocampi and cortices was found by 14 days, and persisted up to 60 days following ICV-STZ infusion. Mitochondrial state-3 respiration was unaltered in these brain regions by 14 days, but significantly decreased from 21 days after STZ administration. DRP-1 expression was significantly increased in the hippocampi and cortices of these animals 21 days after infusion, but persisted only in the hippocampi up to 60 days. Congophilic granules indicative of amyloidosis were detected in the hippocampus by 21 days. CONCLUSION: Our results suggest that the non-genetic sporadic AD (sAD) rat model developed by single-time STZ-ICV infusion exhibits protein aggregation and dementia probably resulting from increased mitochondrial fragmentation and functional aberrations. The present study reinforces the validity of this model for studying pathogenesis and potential therapies of sAD. PMID- 26159197 TI - A Co-Module Regulated by Therapeutic Drugs in a Molecular Subnetwork of Alzheimer's Disease Identified on the Basis of Traditional Chinese Medicine and SAMP8 Mice. AB - There are currently no approved effective therapies for Alzheimer's disease (AD). AD is a classic, multifactorial, complex syndrome. Thus, a polypharmacological or multitargeted approach to AD might provide better therapeutic benefits than monotherapies. However, it remains elusive which biological processes and biomolecules involved in the pathophysiologic processes of AD would constitute good targets for multitargeted therapy. This study proposes that a co-module, consisting of biological processes, cellular pathways and nodes, in a molecular subnetwork perturbed by different therapeutic drugs may be the optimal therapeutic target for an AD multitarget-based intervention. Based on this hypothesis, genes regulated in the hippocampus and cortex of senescence accelerated mouse prone-8 (SAMP8) mice by traditional Chinese medicine (TCM) prescriptions with different constituents and the same beneficial effects on AD, including the decoctions Liu-Wei-Di-Huang (LW), Ba-Wei-Di-Huang (BW), Danggui Shaoyao-San (DSS), Huang-Lian-Jie-Du (HL) and Tiao-Xin-Fang (TXF), were investigated via cDNA microarray, and the perturbed subnetworks were constructed and interpreted. After comparing 15 perturbed subnetworks based on genes affected by LW, BW, HL, DSS and TXF, the results showed that the most important common nodes perturbed by these interventions in the brains of SAMP8 mice were RPS6KA1 and FHIT, and that other important common nodes included UBE2D2, STUB1 and AMFR. These five drugs simultaneously and significantly disturbed the regulation of apoptosis and protein ubiquitination among biological processes. These nodes and processes were key components of the co-module regulated by therapeutic drugs in a molecular subnetwork of AD. These results suggest that targeting candidate regulator of apoptosis and protein ubiquitination might be effective for AD treatment, and that RPS6KA1, FHIT, UBE2D2, STUB1 and AMFR might be optimal combinational targets of an AD multitarget-based therapy. PMID- 26159196 TI - Long-Term Effects of Intracerebroventricular Streptozotocin Treatment on Adult Neurogenesis in the Rat Hippocampus. AB - Altered adult hippocampal neurogenesis (AN) plays a role in the etiopathology of Alzheimer's disease (AD), a disorder characterized by a progressive loss of memory and spatial orientation impairment. Diabetes is shown to be one risk factor for the development of the sporadic form of AD (sAD), which affects >95% of AD patients. Streptozotocin intracerebroventricularily (STZ icv) treated rats, which develop an insulin-resistant brain state and learning and memory deficits preceding amyloid beta and tau pathology, may act as an appropriate animal model for sAD. The goal of our quantitative immunohistochemistry study was to compare short-term (1 month) and long-term (3 months) effects of STZ icv treatment on different AN stages. Applying MCM2 antibodies we quantified cell (e.g. stem cell) proliferation, by the use of NeuroD and DCX antibodies we analyzed immature neurons. BrdU incorporation with approximately 27 days of survival before sacrifice allowed us to quantify and identify surviving newborn cells. Performing co-localization studies with antibodies detecting BrdU and cell-type specific markers we could confirm that STZ treatment does not affect the differentiation fate of newly generated cells. Whereas STZ icv treatment does not seem to considerably influence cell proliferation over a shortterm period (1 month), in the long-term (3 months) it significantly decreased generation of immature and mature neurons. This reduction seen after 3 months was specific for the septal hippocampus, discussed to be important for spatial learning. Moreover, AN changes display the same timeline as the development of amyloid beta pathology in this animal model of sAD. PMID- 26159198 TI - Functional Connectivity Hubs Could Serve as a Potential Biomarker in Alzheimer's Disease: A Reproducible Study. AB - Cortical hubs that link functionally specialized neural systems are crucial for cognition. Evidence suggests that the location and organization of hubs are related to Alzheimer's disease (AD). However, two issues remain unclear: (i) where and how hubs change in AD, and (ii) whether hubs could be a potential pre diagnosis biomarker for mild cognitive impairment (MCI)--a prodromal phase of AD. Accordingly, we examined the functional connectivity density (FCD) in two cohorts of resting-state functional magnetic resonance imaging (fMRI) scans (26 AD, 27 controls; 33 AD, 21 controls) and revealed consistently vulnerable FCD hub regions in AD compared with controls: within the default mode network, short range FCD decreases in the posterior cingulate cortex and increases in the medial prefrontal cortex; within the frontal lobe, long-range FCD increases in the medial prefrontal cortex, superior frontal gyrus and middle frontal gyrus. Furthermore, FCD correlates with cognitive score and could distinguish MCI from controls with high accuracy (71.08% in dataset 1, 81% in dataset 2). By reflecting a robust and reproducible global shift in brain functions, FCD provides an fMRI biomarker for the underlying mechanism in AD. PMID- 26159199 TI - Anti-dementia drugs-related changes in gait performance while single and dual tasking in patients with Alzheimer disease: a meta-analysis. AB - BACKGROUND: The effects of anti-dementia drugs on gait performance in Alzheimer disease (AD) are questionable. The objective of this meta-analysis was to examine the effects of anti-dementia drugs on the mean value and the coefficient of variation (CoV) of stride time among patients with AD while taking into account the type of drugs (i.e., acetylcholinesterase inhibitors [AChEIs] versus memantine) and the walking conditions (i.e., single versus dual-task). METHODS: An English and French Medline search was conducted in March 2015, with no limit of date, using the Medical Subject Headings terms "pharmaceutical preparations" combined with terms "Pharmaceutical preparations" OR "Therapeutic uses" OR "Drug substitution" OR "Drugs essential" OR "Drugs, Generic" OR "Psychotropic drugs" combined with "Delirium" OR "Dementia" OR "Amnestic" OR "Cognitive disorders" AND "Gait" OR "Gait Ataxia" OR "Gait disorders, Neurologic" OR "Gait apraxia". Fixed effects meta-analyses were used to examine anti-dementia drugs-related changes in mean value and CoV of stride time. RESULTS: Of the 66 identified abstracts, 5 (7.6%) were included in the meta-analysis. Inter-group comparison of between visit change underscored a significant decrease in CoV of stride time (P<0.004) in intervention group compared to control group, whatever the pooled analysis considered, but no significant change in the mean value (P>0.06). Intra-group changes in stride time parameters following the use of anti-dementia drugs showed a significant decrease for memantine (P<0.001) and while pooling AChEIs and memantine (P<0.001) under single task condition. Under dual task condition, only AChEIs improved significantly stride time parameters (P=0.002). CONCLUSION: Anti dementia drugs demonstrated a significant improvement of gait performance with specific class effect depending on the walking conditions and on the type of stride time parameters considered. PMID- 26159200 TI - Serum Fragments of Tau for the Differential Diagnosis of Alzheimer's Disease. AB - Differential diagnosis of AD is still a challenge due to overlapping features with other types of dementia. Biomarkers for the differential diagnosis of AD can improve the diagnostic value of the disease and ensure an appropriate treatment of patients. The aim of this study was to evaluate the potential of two neo epitope fragments of Tau as serum biomarkers for differential diagnosis of AD. The neo-epitope fragments of Tau were assessed in a cross-sectional cohort of subjects with AD, MCI, other dementias or subjects with non-dementia related memory complaints. The two Tau neo-epitope fragments were an ADAM10-generated fragment (Tau-A) and a caspase-3-generated fragment (Tau-C). The serum levels of the fragments were measured by two competitive ELISAs detecting Tau-A and Tau-C, respectively. Tau-A and Tau-C were able to separate subjects with AD and MCI from those with other dementias (p<0.0042 and p<0.05), and Tau-A could also discriminate between AD and MCI patients and subjects with non-dementia related memory complaints (p<0.05). Tau-A showed a significantly greater discrimination between AD and MCI subjects and patients with other dementias when compared to CSF biomarkers t-Tau and p-Tau. The ability of Tau-A to differentiate between AD and MCI from other dementias was comparable with CSF Abeta1-42, t-Tau/Abeta1-42 and p-Tau/Abeta1-42. The separation between the diagnostic groups was significantly improved when the CSF biomarkers as well as age and BMI were used in combination with Tau-A (AUC=0.87, 95% CI: 0.75-0.94) (p<0.0001). In conclusion, this study shows that a neoepitope fragment of Tau detected in serum can provide guidance on the differential diagnosis of AD. PMID- 26159201 TI - Effect of PSEN1 mutations on MAPT methylation in early-onset Alzheimer's disease. AB - The MAPT gene is a risk locus for multiple neurodegenerative diseases, including idiopathic Parkinson's and Alzheimer's disease. We examined whether altered DNA methylation of the MAPT promoter, with its potential to modulate gene expression, was a common phenomenon in Alzheimer's disease patients with differing aetiologies. We measured MAPT promoter methylation in a brain tissue cohort of early-onset Alzheimer's disease (EOAD) with defined causative mutations in the PSEN1 gene (Normal = 10, PSEN1 AD = 10), and idiopathic late-onset Alzheimer's disease (Normal = 12, LOAD = 12). We found a brain-region-specific decrease in MAPT promoter methylation in PSEN1 AD patients. Overexpression of PSEN1 reduced MAPT promoter activity in an in vitro luciferase study, and led to an increase in methylation of the endogenous MAPT promoter. Overexpression of PSEN1 with a deletion of exon 9 mutation (Deltaex9) led to a smaller reduction in MAPT promoter activity relative to wild-type PSEN1 in the luciferase assay, consistent with a decreased ability to modulate endogenous MAPT gene methylation. Our study indicates a novel effect of PSEN1 on MAPT methylation, and suggests a mutation specific effect of the PSEN1 Deltaex9 mutation. PMID- 26159202 TI - Prevalence of Sinusitis Detected by Magnetic Resonance Imaging in Subjects with Dementia or Alzheimer's Disease. AB - BACKGROUND: It has been reported that periodontitis is associated with Alzheimer's disease. However, the association between paranasal sinusitis and Alzheimer's disease has not been studied, although olfactory dysfunction frequently precedes the progress of dementia or Alzheimer's disease. METHODS: We studied 783 patients (283 men, 500 women; mean age 77.0 +/- 7.9 years) who visited the Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, and 2139 control subjects who participated in a population-based study conducted by the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA) in Japan. Sinusitis was evaluated using magnetic resonance imaging (MRI) according to the Lund-Mackay scoring system. A sinusitis score of >= 4 was classified as positive and a score of <= 3 was classified as negative. RESULTS: The prevalence of positive sinusitis was 6.3% in patients with a mini-mental state examination (MMSE) score of < 24 (n = 507), and 5.7% in patients with Alzheimer's disease (n = 280). The rate of positive sinusitis was7.2% in the control group. The prevalence of sinusitis was not significantly different between normal controls and patients with dementia or Alzheimer's disease after adjustments for age and sex. The rate of positive sinusitis was higher in male than in female subjects in both groups. CONCLUSION: The prevalence of sinusitis in patients with Alzheimer's disease or dementia was not higher than in the general population. PMID- 26159203 TI - A Cyclooxygenase-2 Inhibitor Reduces Vascular Wall Thickness and Ameliorates Cognitive Impairment in a Cerebral Small Vessel Diseases Rat Model. AB - Cerebral small vessel disease (CSVD) is a group of diseases that originate from changes in cerebral small vessels and that cause many conditions, such as cognitive impairment. However, there is no effective therapy for these diseases. Recent studies have suggested that inflammation is associated with this disease. Cyclooxygenase-2 (cox-2) is an inflammatory mediator; however, whether a cox-2 inhibitor could protect against the CSVD progression remains unknown. In the present study, stroke-prone spontaneously hypertensive rats (SHRsp) were used as a model of CSVD, and Sprague Dawley (SD) rats served as the control. SHRsp were treated with the cox-2 inhibitor celecoxib or vehicle. The Morris water maze test was performed, and vascular morphometry and the expression of collagen I and fibronectin were examined in cerebral small vessels and cerebral tissue. The results revealed that thickened small veesel walls, increased expression of collagen I and fibronectin and impaired cognitive function in SHRsp compared with SD rats. Additionally, celecoxib significantly down-regulated the expression of collagen I and fibronectin, attenuated the increase in vascular wall thickness and ameliorates the cognitive impairment. Our study indicated that this cox-2 inhibitor may serve as a promising candidate for the pharmacological intervention of CSVD. PMID- 26159204 TI - Quantitative MUPET Imaging of Cerebral Glucose Metabolism and Amyloidosis in the TASTPM Double Transgenic Mouse Model of Alzheimer's Disease. AB - Positron emission tomography studies of cerebral glucose utilization and amyloid beta deposition with fluoro-deoxy-D-glucose ([(18)F]-FDG) and amyloid tracers have shown characteristic pathological changes in Alzheimer's Disease that can be used for disease diagnosis and monitoring. Application of this technology to preclinical research with transgenic animal models would greatly facilitate drug discovery and further understanding of disease processes. The results from preclinical studies with these imaging biomarkers have however been highly inconsistent, causing doubts over whether animal models can truly replicate an AD like phenotype. In this study we performed in vivo imaging with [(18)F]-FDG and [(18)F]-AV45 in double transgenic TASTPM mice, a transgenic model that been previously demonstrated high levels of fibrillar amyloid-beta and decreases in cerebral glucose utilization with ex vivo techniques. Our results show widespread and significant retention of [(18)F]-AV45 (p < 0.0001) in aged TASTPM mice in addition to significant regional decreases in [(18)F]-FDG uptake (p < 0.05). In vivo quantification of amyloid-beta showed a strong (Pearson's r = 0.7078), but not significant (p = 0.1156), positive correlation with ex vivo measures suggesting some limitations on tracer sensitivity. In the case of [(18)F]-FDG, voxelwise analysis greatly enhanced detection of hypometabolic regions. We further evidenced modest neuronal loss (thalamus p = 0.0318) that could underlie the observed hypometabolism. This research was performed in conjunction with the European Community's Seventh Framework Program (FP7/2007-2013) for the Innovative Medicine Initiative under the PharmaCog Grant Agreement no.115009. PMID- 26159205 TI - Insulin Modulates In Vitro Secretion of Cytokines and Cytotoxins by Human Glial Cells. AB - Alzheimer's disease (AD) is the most common form of dementia worldwide. Type 2 diabetes (T2D) has been implicated as a risk factor for AD. Since T2D is a peripheral inflammatory condition, and AD brains exhibit exacerbated neuroinflammation, we hypothesized that inflammatory mechanisms could contribute to the observed link between T2D and AD. Abnormal peripheral and brain insulin concentrations have been reported in both T2D and AD. The neurotrophic role of insulin has been described; however, this hormone can also regulate inflammatory responses in the periphery. Therefore we used in vitro human cell culture systems to elucidate the possible effects of insulin on neuroinflammation. We show that human astrocytes and microglia express both isoforms of the insulin receptor as well as the insulin-like growth factor (IGF)-1 receptor. They also express insulin receptor substrate (IRS)-1 and IRS-2, which are required for propagation of insulin/IGF- 1 signaling. We show that at low nanomolar concentrations, insulin could be pro-inflammatory by upregulating secretion of interleukin (IL)-6 and IL-8 from stimulated human astrocytes and secretion of IL-8 from stimulated human microglia. This effect dissipates at higher insulin concentrations. In contrast, insulin at a broader concentration range (10 pM - 1 MUM) reduces the toxicity of stimulated human microglia and THP-1 monocytic cells towards SH-SY5Y neuronal cells. These data show that insulin may regulate the inflammatory status of glial cells by modulating their select functions, which in turn can influence the survival of neurons contributing to the observed link between T2D and AD. PMID- 26159206 TI - Dysfunction of Endoplasmic Reticulum (ER) and Mitochondria (MT) in Alzheimer's Disease: The Role of the ER-MT Cross-Talk. AB - A common feature of neurodegenerative diseases is the formation of misfolded, mostly enzyme resistant proteins. These substances may form toxic assemblies according to the current concept of the neurodegenerative diseases. Overlapping of the misfolded proteins is typical in these disorders. The formation of misfolded proteins and toxic aggregates point to a common pathway of these disorders: failure in normal protein folding in the ER as a consequence of ER stress and mitochondrial energy production. Alzheimer's disease (AD) is a rather heterogeneous, multifactorial disorder with wide clinical heterogeneity and is classified into several subtypes. In AD the processing of the amyloid precursor protein (APP) and formation of toxic beta-amyloid (Abeta) structures occur intraneuronally. Abeta affects both ER and mitochondria and disturbs Ca(2+) homeostasis of the cells. Mitochondrial dysfunction is one of the main pathological events in AD. Mitochondria accumulate Abeta derived from the ER/Golgi or from the mitochondria-associated ER-membranes (MAM). Free radicals, oxidative stress and increasing Ca(2+)-concentration in mitochondria cause decreased ATP production. Mitochondrial dynamic and trafficking are also altered as a result of Abeta toxicity. Synaptic mitochondria show a very high vulnerability. Depletion of Ca(2+) level in the ER results in dysfunction of protein folding and evokes unfolded protein response (UPR), and affects also mitochondria. MAM may play special role in the ER-mitochondria cross talk. Mitochondria themselves (using mitochondria-targeting antioxidants such as MitoQ) could be a special target for AD treatment. Another targets are the UPR cascade proteins (PERK, IRE1, ATF6) and receptors involved in Ca(2+) -level stabilization of the ER (Ryr, IP3R). PMID- 26159207 TI - Resonance frequency analysis (RFA) and insertional torque (IT) stability comparisons of implants placed using osteotomes versus drilling techniques: A preliminary case study. AB - OBJECTIVE: Poor bone density in the posterior maxilla often presents challenges in achieving implant stability. Insertional torque (IT) and resonance frequency analysis (RFA) have been used to objectively monitor the process of osseointegration. This study was designed to quantitatively assess the primary and secondary stability of fixtures placed using the osteotome or conventional drilling technique, in soft bone. The study also assessed if there was a correlation between IT and RFA measurements. METHOD AND MATERIALS: Sixteen implants of a standardized dimension were randomly assigned to two groups: osteotome or conventional drilling. IT was taken at the time of placement. RFA was recorded at baseline and 30, 60, and 90 days. RESULTS: Average IT and RFA were 36 Ncm (range 25-45 Ncm) and 61.5 implant stability quotient (ISQ; range 44 72 ISQ), respectively. RFA in the osteotome group increased from day 0 to day 30 (63.5 to 68.0 ISQ) whereas it decreased in the conventional drilling group (65.9 to 56.6 ISQ). At 90 days, both groups showed similar results. No statistically significant difference between IT and RFA was found across all time intervals. CONCLUSION: IT and ISQ values were shown to fluctuate depending on various local anatomical factors such as density of the bone. Additional clinical and radiographic studies are needed in type 1 to 4 bone to determine the utilization of RFA and IT for routine implant surgery. Adequate stability measurements are critical for implant placement. Future guidelines and knowledge of stability and bone density values may help in establishing loading protocols and improving success rate. PMID- 26159208 TI - Does the hybrid light source (LED/laser) influence temperature variation on the enamel surface during 35% hydrogen peroxide bleaching? A randomized clinical trial. AB - OBJECTIVE: The present study investigated how a hybrid light source (LED/laser) influences temperature variation on the enamel surfaces during 35% hydrogen peroxide (HP) bleaching. Effects on the whitening effectiveness and tooth sensitivity were analyzed. METHOD AND MATERIALS: Twenty-two volunteers were randomly assigned to two different treatments in a split-mouth experimental model: group 1 (control), 35% HP; group 2 (experimental), 35% HP + LED/laser. Color evaluation was performed before treatment, and 7 and 14 days after completion of bleaching, using a color shade scale. Tooth sensitivity was assessed using a visual analog scale (VAS; before, immediately, and 24 hours after bleaching). During the bleaching treatment, thermocouple channels positioned on the tooth surfaces recorded the temperature. Data on color and temperature changes were subjected to statistical analysis (alpha = 5%). Tooth sensitivity data were evaluated descriptively. RESULTS: Groups 1 and 2 showed mean temperatures (+/- standard deviation) of 30.7 +/- 1.2 degrees C and 34.1 +/ 1.3 degrees C, respectively. It was found that there were statistically significant differences between the groups, with group 2 showing higher mean variation (P < .0001). The highest temperature variation occurred for group 2, with an increase of 5.3 degrees C at the enamel surface. The color change results showed no differences in bleaching between the two treatment groups (P = .177). The variation of the average temperature during the treatments was not statistically associated with color variation (P = .079). Immediately after bleaching, it was found that 36.4% of the subjects in group 2 had mild to moderate sensitivity. In group 1, 45.5% showed moderate sensitivity. In both groups, the sensitivity ceased within 24 hours. CONCLUSION: Hybrid light source (LED/ laser) influences temperature variation on the enamel surface during 35% HP bleaching and is not related to greater tooth sensitivity. PMID- 26159209 TI - Socket seal surgery: Clinical uses in implant dentistry and guided bone regeneration procedures for single tooth replacement in the esthetic zone. AB - Restoring failing anterior teeth with a dental implant is considered a complex treatment even with thorough biologic knowledge of the situation. The goal is to produce a result in which the labial soft tissues and the papillae remain stable over time. Treatment of the fresh extraction socket in the alveolar ridge presents a challenge in everyday clinical practice. Regardless of the subsequent treatment, maintenance of the ridge contour will frequently facilitate all further therapeutic steps. Socket seal surgery and socket preservation in combination with immediate, early, or delayed implant placement can be valuable procedures for single tooth replacement. However, their potential as ridge preservation techniques in these different situations still needs to be demonstrated. The use of these procedures is illustrated in three consecutive cases. PMID- 26159210 TI - Clinical evaluation of periodontal disease in patients with rheumatoid arthritis: A cross-sectional study. AB - OBJECTIVE: The aim of this study was to determine the presence of periodontal disease among patients with rheumatoid arthritis (RA) in comparison with a control group. METHOD AND MATERIALS: The study included 44 patients diagnosed with RA according to American Rheumatism Association (ARA) criteria, who were attending the Morales Meseguer Hospital Rheumatology Service (Murcia, Spain), and 41 control subjects. Patients younger than 18 years or patients suffering systemic diseases that could affect the immune system were excluded. Age, sex, smoking habits, alcohol consumption, and body mass index were registered. Each patient underwent a full periodontal examination. RESULTS: Bleeding on probing was significantly greater in the RA group (0.9 +/- 0.36) than the control (P < .001). The Plaque Index was significantly higher in the RA group (0.76 +/- 0.34) versus the control group (0.55 +/- 0.2) (P < .001). RA patients showed a 0.13 increased risk of periodontal disease (95% confidence interval, 0.05-0.37). CONCLUSION: Patients with RA suffered a higher risk of periodontal disease and for this reason these patients must be instructed to intensify their oral hygiene regimes. PMID- 26159211 TI - Radiographic outcomes following treatment of intrabony defects by freeze-dried bone allograft combined with enamel matrix derivative: A retrospective study. AB - OBJECTIVE: The aim of this study was to evaluate the radiographic outcomes following regenerative surgery using enamel matrix derivative (EMD) + freeze dried bone allograft (FDBA). METHOD AND MATERIALS: In total, 74 two- or three wall intrabony defects were treated by a combination of EMD+FDBA followed by supportive periodontal therapy (SPT) for a minimum of 2 years. Radiographs were taken at baseline and after the follow-up period. The measurements taken were: baseline defect angle, CEJ to the coronal part of the alveolar bone crest (CEJ BC), CEJ to the apical part of the intrabony defect (CEJ- BD), the intrabony component of the defect (DL), and the defect angle between the lines CEJ-BC and CEJ-BD. RESULTS: Baseline defect angles were divided into three groups: first group defect angle <= 22 degrees; second group 22 degrees to 36 degrees; and third group >= 36 degrees. A significant difference in DL following treatment was found in all groups (6.930 mm, 4.202 mm, and 2.073 mm respectively; P < .01). The largest difference in DL was measured for the first group. A positive linear correlation was found between baseline values of the defect angle, CEJ-BD, CEJ BC, and the later change in DL (P < .01). CONCLUSION: The use of EMD+FDBA results in radiographic bone gain. Narrow defect angle and the depth of the intrabony component have significant positive correlation to radiographic bone gain. PMID- 26159212 TI - Volumetric comparison of three different innovative bone collecting devices for autogenous bone grafts. AB - OBJECTIVE: The aim of this study was to evaluate the clinical relevance of three different bone collecting devices in a volumetric comparison. METHOD AND MATERIALS: Bone harvesting for the collection of bone particles was performed on bovine mandibles. Three different types of bone collecting devices (Tests 1, 2, and 3) were used. Ten drilling sites in each group were prepared and bone particles were collected. Bone particles were sieved twice in sieves with 500 MUm and 1,000 MUm openings. The bone particles were divided into three groups: < 500 MUm (SP), 500-1,000 MUm (MP), and >1,000 MUm (LP). Total wet volume, fractional wet volume, fractional dry volume, and weight were measured. The shape of the dried particles was examined using a microscope. RESULTS: All particles in all three groups had a wood shaving-like appearance. With Test 1 and Test 2, LP were the most common (0.510 +/- 0.064 mL, 0.430 +/- 0.067 mL), and in Test 3, MP was the most common (0.112 +/- 0.019 mL). Among the SP and MP, the wet volume of Test 3 was significantly greater than those of Tests 1 and 2 (P < .001). However, among the LP, the wet volume sequentially increased from Test 1, to Test 2, and Test 3 (P < .001). The proportion of dry volume was similar to that of wet volume. CONCLUSION: Three innovative bone collecting devices could collect comparable amounts of bone particles to commercially available bone graft materials. PMID- 26159213 TI - Restoring proximal cavities of molars using the proximal box elevation technique: Systematic review and report of a case. AB - OBJECTIVE: For decades, dental restorative treatment of large and deep cavities of posterior teeth has been adequately ensured by amalgam or by indirect gold restorations; with the continuing advancements in material technology and clinical techniques, alternative and more esthetic types of restorations have become feasible. Proximal box elevation (PBE) using composite resins has been advocated for relocating subgingival cavity outlines; treatment success and effects of PBE require documentation. DATA SOURCES: An electronic search was performed on several literature databases to identify relevant articles published in indexed journals until April 2015. METHOD AND MATERIALS: The authors independently screened the relevant papers found (PBE with composite resins). RESULTS: This paper compiles the current knowledge about PBE (which is predominantly based on laboratory research, in particular with a focus on microleakage and marginal adaptation), revealing that flowable composites allow for a stepwise elevation of proximal cavity floors, thus simplifying treatment of deep lesions, and broadening the restorative spectrum. A case report revealing an advanced caries lesion and demonstrating the clinical application of the PBE technique together with an indirect computer-aided design/computer-assisted manufacture (CAD/CAM) all-ceramic restoration is presented, assuring the practitioner's familiarity with effective placement techniques. CONCLUSION: PBE represents a promising two-step treatment regimen, simultaneously encompassing the benefits of immediate dentin sealing and facilitating direct or indirect adhesive restorations of cavities with margins located beneath the gingival tissues. However, high-quality randomized clinical trials are required to confirm the laboratory outcomes. PMID- 26159215 TI - Isoflurane Preconditioning Promotes the Survival and Migration of Bone Marrow Stromal Cells. AB - BACKGROUND: Preconditioning with the volatile anesthetic isoflurane exerts protective effects in animal models of ischemia. The cytoprotective effects of isoflurane are dependent on the expression of hypoxia inducible factor-1 (HIF-1), a dimeric transcription factor that mediates cellular responses to hypoxia. METHODS: We investigated the effect of isoflurane preconditioning on bone marrow stromal cell (BMSC) survival and function. RESULTS: Short exposures to low isoflurane concentrations promoted in vitro survival and migration of BMSCs, whereas long exposures and high doses had the opposite effect. At specific doses and times, isoflurane upregulated the expression of HIF-1alpha and the stromal derived factor-1 receptor CXCR4, and induced the activation of Akt, similar to hypoxia, and the effect of isoflurane was abrogated by silencing of HIF-1alpha or inhibition of PI3K/Akt signaling. In vivo experiments showed that isoflurane preconditioning increased the engraftment of BMSCs into the ischemic brain and improved functional recovery in a mouse model of stroke. CONCLUSION: Isoflurane preconditioning at specific doses and times improves the survival and function of BMSCs through the upregulation of CXCR4 via a mechanism involving HIF-1alpha expression and the PI3K/Akt pathway, suggesting that anesthetic preconditioning could be developed as a strategy to improve the efficiency of cell therapy. PMID- 26159214 TI - Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs. AB - Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses >60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets. PMID- 26159216 TI - Induction of Angiogenesis by Matrigel Coating of VEGF-Loaded PEG/PCL-Based Hydrogel Scaffolds for hBMSC Transplantation. AB - hBMSCs are multipotent cells that are useful for tissue regeneration to treat degenerative diseases and others for their differentiation ability into chondrocytes, osteoblasts, adipocytes, hepatocytes and neuronal cells. In this study, biodegradable elastic hydrogels consisting of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(epsilon-caprolactone) (PCL) scaffolds were evaluated for tissue engineering because of its biocompatibility and the ability to control the release of bioactive peptides. The primary cultured cells from human bone marrow are confirmed as hBMSC by immunohistochemical analysis. Mesenchymal stem cell markers (collagen type I, fibronectin, CD54, integrin1beta, and Hu protein) were shown to be positive, while hematopoietic stem cell markers (CD14 and CD45) were shown to be negative. Three different hydrogel scaffolds with different block compositions (PEG:PCL=6:14 and 14:6 by weight) were fabricated using the salt leaching method. The hBMSCs were expanded, seeded on the scaffolds, and cultured up to 8 days under static conditions in Iscove's Modified Dulbecco's Media (IMDM). The growth of MSCs cultured on the hydrogel with PEG/PCL= 6/14 was faster than that of the others. In addition, the morphology of MSCs seemed to be normal and no cytotoxicity was found. The coating of the vascular endothelial growth factor (VEGF) containing scaffold with Matrigel slowed down the release of VEGF in vitro and promoted the angiogenesis when transplanted into BALB/c nude mice. These results suggest that hBMSCs can be supported by a biode gradable hydrogel scaffold for effective cell growth, and enhance the angiogenesis by Matrigel coating. PMID- 26159217 TI - Whole-Body Plethysmography in Suspected Asthma: A Prospective Study of Its Added Diagnostic Value in 302 Patients. AB - BACKGROUND: Whole-body plethysmography (WBP) with bronchial challenge testing to measure the (specific) airway resistance, (s)R(AW), is considered to be a more sensitive diagnostic procedure than spirometry, which can only measure the forced expiratory volume in one second (FEV1). The evidence for the added diagnostic value of WBP is not yet conclusive. METHODS: In a prospective diagnostic study, we carried out WBP with bronchial challenge testing as well as a bronchodilation test in 400 patients with suspected asthma from June 2010 to October 2011. The bronchial provocation test was considered positive if the FEV1 fell by at least 20% and/or the airway resistance doubled, with an increase of the sR(AW) to at least 2.0 kPA * s and/or of the R(AW) to 0.5 kPA * s/L. Follow-up evaluation was performed one year later. RESULTS: The prevalence of asthma in the 302 patients who completed follow-up was 27.5%. The sensitivity of WBP with sR(AW) measurement for asthma was 95.2% (95% confidence interval [CI] 88.3%-98.1%), and its specificity was 81.7% (95% CI 76.1%-86.3%). The sensitivity of FEV1 was 44.6% (95% CI 34.4%-55.3%), and its specificity was 91.3% (95% CI 86.6%-94.4%). The negative predictive value (NPV) of WBP with sR(AW) measurement was 97.8% (95% CI 94.5%-99.1%), while that of FEV1 was 81.3% (95% CI 76.0%-85.7%). The positive predictive value (PPV) of WBP with sR(AW) measurement was 66.4% (95% CI 57.5% 74.2%), while that of FEV1 was 66.1% (95% CI 53.0%-77.1%). CONCLUSION: With sR(AW) measurement, asthma can be ruled out with high certainty. Improving the positive predictive value of testing for asthma remains a challenge, however, as sR(AW) measurement does not yield any increase in specificity. PMID- 26159219 TI - Two Additional Aspects. PMID- 26159218 TI - Thermal Ablation of Renal Tumors: Indications, Techniques and Results. AB - BACKGROUND: About 15,000 persons receive the diagnosis of kidney cancer in Germany every year. Surgical resection is the standard treatment for locally confined tumors, but minimally invasive thermoablative techniques are increasingly being used as well. METHODS: This article is based on publications retrieved by a selective literature search in PubMed regarding the thermoablative techniques now used in clinical practice, with particular attention to radiofrequency ablation (RFA) and cryoablation (CA). RESULTS: RFA and CA are suitable for patients who cannot undergo surgery because of comorbid illnesses or who have contralateral recurrences or a hereditary precancerous condition. The primary technical success rate of these procedures ranges from 88% to 100%. More than 95% of tumors under 3 cm in diameter can be completely ablated. Reported complication rates range from 1% to 7%. New data on long-term outcomes reveal metastasis-free survival rates of 88% to 99% five years after ablation. A major advantage of these procedures is that thermoablation does not impair renal function to any relevant extent and is thus a good option for patients with limited renal function or a single kidney. CONCLUSION: The thermoablative techniques are an important addition to the armamentarium of effective treatments for locally confined renal tumors. The guidelines of the American and European urological societies now list thermoablation with RFA or CA as an option for the treatment of small renal tumors with curative intent. Thermoablation of renal tumors has not yet been studied in randomized controlled trials; these will be needed so that the efficacy of tumor control, survival rates, complication rates, and quality of life after treatment can be reliably evaluated to provide definitive confirmation of the value of interstitial techniques. PMID- 26159220 TI - Bio-psycho-social Aspects of an Overall Treatment Plan. PMID- 26159221 TI - List of Drugs That Can Cause Depression. PMID- 26159222 TI - Not Transferable to Outpatient Care. PMID- 26159223 TI - Hormone Replacement in Patients With Depression. PMID- 26159224 TI - Repetitive Transcranial Magnetic Stimulation. PMID- 26159225 TI - In Reply. PMID- 26159226 TI - Genome-scale long noncoding RNA expression pattern in squamous cell lung cancer. AB - In this study, we aimed to explore the long noncoding RNA expression pattern in squamous cell lung cancer (SQCC) on a genome-wide scale. Total RNAs were extracted from 16 lung SQCC patients' normal and matched lung cancer tissues by Trizol reagent. The expression level of genome-wide scale lncRNA and mRNA was determined by microarray. qRT-PCR was used to validate the lncRNA expression level in 47 patients. Data analyses were performed using R and Bioconductor. A total of 2,748 up and 852 down regulated probes were identified to be significantly and differentially expressed in tumor tissues. The annotation result of their co-expressed mRNAs showed that the most significantly related category of GO analysis was development and differentiation, while the most significantly related pathway was cell cycle. Subgroup analysis identified that 46 and 18 probes were specifically differentially expressed in smoking and moderately differentiated tumors, respectively. Our study indicated that clusters of lncRNAs were significantly and differentially expressed in SQCC compared with normal tissues in the same subject. They may exert a significant role in lung cancer development and could be potential targets for future treatment of SQCC. PMID- 26159227 TI - Metagenomic insights into strategies of aerobic and anaerobic carbon and nitrogen transformation in boreal lakes. AB - Thousands of net-heterotrophic and strongly stratifying lakes dominate the boreal landscape. Besides their central role as emitters of greenhouse gases, we have only recently begun to understand the microbial systems driving the metabolic processes and elemental cycles in these lakes. Using shotgun metagenomics, we show that the functional potential differs among lake types, with humic lakes being particularly enriched in carbon degradation genes. Most of the metabolic pathways exhibit oxygen- and temperature-dependent stratification over depth, coinciding with shifts in bacterial community composition, implying that stratification is a major factor controlling lake metabolism. In the bottom waters, rare and poorly characterized taxa, such as epsilon-Proteobacteria, but also autotrophs, such as photolithotrophic Chlorobia were abundant. These oxygen depleted layers exhibited high genetic potential for mineralization, but also for fixation of carbon and nitrogen, and genetic markers for both methane production and oxidation were present. Our study provides a first glimpse of the genetic versatility of freshwater anoxic zones, and demonstrates the potential for complete turnover of carbon compounds within the water column. PMID- 26159228 TI - Ancient DNA sequence revealed by error-correcting codes. AB - A previously described DNA sequence generator algorithm (DNA-SGA) using error correcting codes has been employed as a computational tool to address the evolutionary pathway of the genetic code. The code-generated sequence alignment demonstrated that a residue mutation revealed by the code can be found in the same position in sequences of distantly related taxa. Furthermore, the code generated sequences do not promote amino acid changes in the deviant genomes through codon reassignment. A Bayesian evolutionary analysis of both code generated and homologous sequences of the Arabidopsis thaliana malate dehydrogenase gene indicates an approximately 1 MYA divergence time from the MDH code-generated sequence node to its paralogous sequences. The DNA-SGA helps to determine the plesiomorphic state of DNA sequences because a single nucleotide alteration often occurs in distantly related taxa and can be found in the alternative codon patterns of noncanonical genetic codes. As a consequence, the algorithm may reveal an earlier stage of the evolution of the standard code. PMID- 26159229 TI - Preferred Molecular Orientation of Coumarin 343 on TiO2 Surfaces: Application to Dye-Sensitized Solar Cells. AB - The dye...TiO2 interfacial structure in working electrodes of dye-sensitized solar cells (DSCs) is known to influence its photovoltaic device performance. Despite this, direct and quantitative reports of such structure remain sparse. This case study presents the application of X-ray reflectometry to determine the preferred structural orientation and molecular packing of the organic dye, Coumarin 343, adsorbed onto amorphous TiO2. Results show that the dye molecules are, on average, tilted by 61.1 degrees relative to the TiO2 surface, and are separated from each other by 8.2 A. These findings emulate the molecular packing arrangement of a monolayer of Coumarin 343 within its crystal structure. This suggests that the dye adsorbs onto TiO2 in one of its lowest energy configurations; that is, dye...TiO2 self-assembly is driven more by thermodynamic rather than kinetic means. Complementary DSC device tests illustrate that this interfacial structure compromises photovoltaic performance, unless a suitably sized coadsorbant is interdispersed between the Coumarin 343 chromophores on the TiO2 surface. PMID- 26159230 TI - Embryonic Stem Cell-Related Protein L1TD1 Is Required for Cell Viability, Neurosphere Formation, and Chemoresistance in Medulloblastoma. AB - Misexpression of stem cell-related genes may occur in some cancer cells, influencing patient's prognosis. This is the case of medulloblastoma, a common and clinically challenging malignant tumor of the central nervous system, where expression of the pluripotency factor, OCT4, is correlated with poor survival. A downstream target of OCT4, L1TD1 (LINE-1 type transposase domain-containing protein 1 family member), encodes a novel embryonic stem cell (ESC)-related protein involved in pluripotency and self-renewal of ESCs. L1TD1 is still poorly characterized and its expression pattern and function in cancer cells are virtually unknown. Although normally restricted to non-neoplastic undifferentiated cells and germ cells, we found that high L1TD1 expression also occurs in medulloblastoma cells, reaching levels similar to those found in ESCs, and is correlated with poor prognosis. Conversely to what is reported during normal cell differentiation, when differentiated cells remain healthy, despite L1TD1 downregulation, depletion of L1TD1 protein levels by targeted gene silencing significantly reduced medulloblastoma cell viability, inhibiting cell proliferation and inducing apoptosis. More strikingly, L1TD1 depletion downregulated expression of the neural stem cell markers, CD133 and Nestin, inhibited neurosphere generation capability, and sensitized medulloblastoma cells to temozolomide and cisplatin, two chemotherapeutic agents of clinical relevance in medulloblastoma treatment. Our findings provide insights about the contribution of pluripotency-related genes to a more aggressive tumor phenotype through their involvement in the acquisition of stem-like properties by cancer cells and point out L1TD1 as a potential therapeutic target in malignant brain tumors. PMID- 26159231 TI - Bi-Institutional Comparison of Robot-Assisted Laparoscopic Versus Open Ureteroureterostomy in the Pediatric Population. AB - PURPOSE: Ureteroureterostomy (UU) is a useful surgical option for the management of duplication anomalies as well as obstructed single system ureters for children. We aimed to evaluate the safety, efficacy, and outcomes of robot assisted laparoscopic UU (RALUU) compared with open UU (OUU) in the pediatric population. PATIENTS AND METHODS: A retrospective review was performed at two institutions including six surgeons' experience with all cases of RALUU and OUU from January 2005 to June 2014. Indications for a surgical procedure included duplex systems with an upper pole ectopic ureter, obstructed ureterocele or lower pole vesicoureteral reflux, and obstruction in a single system. Transureteroureterostomy, laparoscopic UU, and major reconstruction cases where UU was the secondary procedure were excluded. RESULTS: There were 25 RALUU and 19 OUU cases included. All cases involved duplex systems except two proximal to distal anastomoses in single system obstructed kidneys. RALUUs were more likely to be performed proximally (P = 0.01) and with the use of cystoscopy and stent placement (P = <0.0001). Operative times and estimated blood loss were similar between the two groups. Postoperative complications included four febrile urinary tract infections in each group, one recurrence of nonfebrile urinary tract infection in the open group, and one postoperative obstruction at the ureterovesical junction because of attempted stent placement necessitating nephrostomy tube placement in the open group. This OUU patient was the only one to demonstrate more severe hydronephrosis after surgery on initial follow-up imaging that was again unrelated to the open UU procedure. RALUU had shorter hospital stays by 0.5 days (P = 0.04). CONCLUSION: Robot-assisted laparoscopic UU is a safe and effective alternative to open UU in children with duplication anomalies and single system obstructed ureters. Operative times and complication rates were comparable with slightly shorter length of hospitalization in robotic cases. PMID- 26159232 TI - First Nomogram Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients Undergoing Radioisotope Guided Sentinel Lymph Node Dissection. AB - INTRODUCTION: Existing nomograms predicting lymph node involvement (LNI) in prostate cancer (PCa) are based on conventional lymphadenectomy. The aim of the study was to develop the first nomogram for predicting LNI in PCa patients undergoing sentinel guided pelvic lymph node dissection (sPLND). MATERIALS AND METHODS: Analysis was performed on 1,296 patients with PCa who underwent radioisotope guided sPLND and retropubic radical prostatectomy (2005-2010). Median prostate specific antigen (PSA): 7.4 ng/ml (IQR 5.3-11.5 ng/ml). Clinical T-categories: T1: 54.8%, T2: 42.4%, T3: 2.8%. Biopsy Gleason sums: <= 6: 55.1%, 7: 39.5%, >= 8: 5.4%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram for predicting LNI. Accuracy was quantified using the area under the curve (AUC). RESULTS: The median number of LNs removed was 10 (IQR 7-13). Overall, 17.8% of patients (n = 231) had LNI. The nomogram had a high predictive accuracy (AUC of 82%). All the variables were statistically significant multivariate predictors of LNI (p = 0.001). Univariate predictive accuracy for PSA, Gleason sum and clinical stage was 69, 75 and 69%, respectively. CONCLUSIONS: The sentinel nomogram can predict LNI at a sPLND very accurately and, for the first time, aid clinicians and patients in making important decisions on the indication of a sPLND. The high rate of LN+ patients underscores the sensitivity of sPLND. PMID- 26159233 TI - Effects of Maternal Cortisol during Pregnancy on Children's Blood Pressure Responses. AB - BACKGROUND: It is well established that birth weight has an effect on subsequent blood pressure. Predominantly experimental studies have also reported effects of altered corticosteroid levels on subsequent cardiovascular responses. In the current study, we have examined the effects of both birth weight and maternal cortisol levels in a cohort of mothers and their pre-adolescent children. PROCEDURE: A total of 216 women and their 7- to 9-year-old children comprised the cohort. The women had been assessed for plasma cortisol during the first (n = 71), second (n = 72) and third (n = 73) trimester. Maternal cortisol had been measured on a fasting sample taken between 9 and 11 a.m. The children's blood pressure and heart rate were recorded in the resting state, in response to a 10 min video game stress challenge and during recovery. Resting values, incremental responses to stress and recovery were evaluated. OBSERVATION: Maternal cortisol levels increased with duration of pregnancy. There were inverse correlations between birth weight and all haemodynamic measures. The positive associations between maternal cortisol and children's haemodynamic measures were most evident in the first and second trimesters. Birth weight was inversely related to maternal cortisol. In multiple regression analyses, the effects of maternal cortisol were more consistent than those of birth weight. CONCLUSION: Both birth weight and maternal cortisol are predictive of children's resting and stress modulated haemodynamic measures. The effects of birth weight may partly mediate the effects of maternal cortisol. PMID- 26159234 TI - Clinical features and outcomes in 154 patients with haemorrhagic moyamoya disease: comparison of conservative treatment and surgical revascularization. AB - OBJECTIVES: Rebleeding is an unsatisfactory outcome for patients with haemorrhagic MMD. This study mainly investigated clinical features and outcomes in haemorrhagic MMD. METHODS: A retrospective review was performed on a total of 154 patients with haemorrhagic MMD comprising 126 surgically treated and 28 conservatively treated patients. RESULTS: There were 102 female and 52 male patients with a mean age at the initial bleeding of 33.95 years. Preoperative rebleeding occurred in 37 patients, and multivariate Cox regression analysis demonstrated that age at the time of initial bleeding (P < 0.001, HR = 1.093) was a risk factor for preoperative rebleeding. Of 124 patients with surgical revascularization, perioperative ischaemic stroke occurred in five (4.03%) and intracranial bleeding in four (3.23%). The mean follow-up period was 36.12 months. Recurrent bleeding occurred in six (10.17%) of 59 patients treated with direct revascularization, seven (20.69%) of 34 patients treated with indirect revascularization, two (6.45%) of 31 patients treated with combined revascularization and six (21.43%) of 28 patients treated conservatively. Kaplan Meier analysis revealed no statistical differences in preventing rebleeding between direct, indirect and combined revascularization and conservative treatment (P = 0.311). CONCLUSIONS: Age at the initial bleeding is a risk factor for rebleeding in haemorrhagic MMD. Although surgical revascularization show the tendency to decrease the rebleeding rate, there is no statistical difference between direct revascularization, indirect revascularization, combined revascularization and conservative treatment in preventing rebleeding. Further study is needed to determine whether surgical revascularization is effective in select population or with certain techniques. PMID- 26159235 TI - CuO nanowire/microflower/nanowire modified Cu electrode with enhanced electrochemical performance for non-enzymatic glucose sensing. AB - CuO nanowire/microflower structure on Cu foil is synthesized by annealing a Cu(OH)2 nanowire/CuO microflower structure at 250 degrees C in air. The nanowire/microflower structure with its large surface area leads to an efficient catalysis and charge transfer in glucose detection, achieving a high sensitivity of 1943 MUA mM(-1) cm(-2), a wide linear range up to 4 mM and a low detection limit of 4 MUM for amperometric glucose sensing in alkaline solution. With a second consecutive growth of CuO nanowires on the microflowers, the sensitivity of the obtained CuO nanowire/microflower/nanowire structure further increases to 2424 MUA mM(-1) cm(-2), benefiting from an increased number of electrochemically active sites. The enhanced electrocatalytic performance of the CuO nanowire/microflower/nanowire electrode compared to the CuO nanowire/microflower electrode, CuO nanowire electrode and CuxO film electrode provides evidence for the significant role of available surface area for electrocatalysis. The rational combination of CuO nanowire and microflower nanostructures into a nanowire supporting microflower branching nanowires structure makes it a promising composite nanostructure for use in CuO based electrochemical sensors with promising analytical properties. PMID- 26159236 TI - Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-kappaB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation. AB - BACKGROUND/AIMS: The effects of H2S on cerebral inflammatory reaction after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remain poorly understood. In this study, we investigated the effects of exogenous 40 ppm and 80 ppm H2S gas on inflammatory reaction and neurological outcome after CA/CPR. METHODS: CA was induced by ventricular fibrillation and followed by CPR. Forty or 80 ppm H2S was inhaled for 1 h immediately following CPR. The levels of IL-1beta, IL-6 and TNF-alpha, the myeloperoxidase (MPO) activity, the expression of iNOS and ICAM-1, and the phosphorylation and translocation of NF-kappaB were evaluated at 24 h after CA/ CPR. The tape removal test, survival rate and hippocampal neuronal counts were investigated at 14 d after CA/CPR. RESULTS: CA/CPR induced significant increases in IL-1beta, IL-6, TNF-alpha and MPO activity. The phosphorylation and translocation of NF-kappaB, and the expression of iNOS and ICAM-1 were increased significantly. Inhalation of 40 or 80 ppm H2S gas decreased these inflammatory cytokines. Furthermore, 40 or 80 ppm H2S inhibited the activation of NF-kappaB and the downstream proinflammatory mediators iNOS and ICAM-1. H2S inhalation also improved neurological function, 14-d survival rate, and reduced hippocampal neuronal loss. CONCLUSION: These results indicated that inhalation of H2S protected against brain injury after CA/CPR. The mechanisms underlying protective effects of H2S were associated with the inhibition of CA/ CPR-induced inflammation reactions by reducing IL-1beta, IL-6 and TNF-alpha, and concomitantly inhibiting the activation and infiltration of neutrophils. The beneficial effects of H2S might be mediated by downregulation of NF-kappaB and the downstream proinflammatory signaling pathway. PMID- 26159237 TI - Radioguided intraoperative detection of ectopic adrenocorticotropic hormone producing carcinoid tumor. PMID- 26159238 TI - Core-shell heterostructured metal oxide arrays enable superior light-harvesting and hysteresis-free mesoscopic perovskite solar cells. AB - To achieve highly efficient mesoscopic perovskite solar cells (PSCs), the structure and properties of an electron transport layer (ETL) or material (ETM) have been shown to be of supreme importance. Particularly, the core-shell heterostructured mesoscopic ETM architecture has been recognized as a successful electrode design, because of its large internal surface area, superior light harvesting efficiency and its ability to achieve fast charge transport. Here we report the successful fabrication of a hysteresis-free, 15.3% efficient PSC using vertically aligned ZnO nanorod/TiO2 shell (ZNR/TS) core-shell heterostructured ETMs for the first time. We have also added a conjugated polyelectrolyte polymer into the growth solution to promote the growth of high aspect ratio (AR) ZNRs and substantially improve the infiltration of the perovskite light absorber into the ETM. The PSCs based on the as-synthesized core-shell ZnO/TiO2 heterostructured ETMs exhibited excellent performance enhancement credited to the superior light harvesting capability, larger surface area, prolonged charge-transport pathways and lower recombination rate. The unique ETM design together with minimal hysteresis introduces core-shell ZnO/TiO2 heterostructures as a promising mesoscopic electrode approach for the fabrication of efficient PSCs. PMID- 26159239 TI - Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Several cohort studies have shown an association between low platelet counts in the first day(s) of life and patent ductus arteriosus (PDA) in preterm infants. However, these results have not been confirmed by other studies. OBJECTIVE: To perform a meta-analysis of all the studies addressing the relationship between platelet counts in the first day(s) of life and PDA in preterm infants. METHODS: PubMed/MEDLINE and EMBASE were searched from their inception until December 2014. Results from 11 cohort studies involving 3,479 preterm infants (gestational age <32 weeks) were pooled using random-effects modeling. RESULTS: Meta-analysis showed a significant positive association between PDA and platelet counts <150 * 10(9)/l [6 studies, risk ratio (RR) = 1.215, 95% CI: 1.027-1.436], between PDA and platelet counts <100 * 10(9)/l (5 studies, RR = 1.255, 95% CI: 1.034-1.525), and between significant PDA (SPDA) and platelet counts <100 * 10(9)/l (5 studies, RR = 1.254, 95% CI: 1.021-1.540). The association between SPDA and platelet counts <150 * 10(9)/l was not statistically significant (6 studies, RR = 1.289, 95% CI: 0.925-1.795). Pooled standard differences in mean platelet counts between infants with and without PDA/SPDA were not statistically different. CONCLUSION: This meta-analysis reveals a marginal but significant association between low platelet counts in the first day(s) of life and PDA/SPDA in very preterm infants. This association needs to be confirmed in prospective studies. PMID- 26159240 TI - Time-dependent effects of unfractionated heparin in patients with ST-elevation myocardial infarction transferred for primary angioplasty. AB - AIMS: Initial thrombolysis in myocardial infarction (TIMI) flow and mortality are related in ST-elevation myocardial infarction (STEMI) patients treated with primary angioplasty (PPCI). It is unclear whether early adjunctive treatment with unfractionated heparin (UFH) is beneficial for coronary patency. We investigated the effect of UFH administered before transfer versus in the catheterization laboratory (CathLab) on initial patency of the infarct related artery (IRA) in transferred STEMI patients treated with PPCI. METHODS AND RESULTS: Consecutive STEMI patients (n=1326, February 2007-December 2013) were allocated in two groups relative to UFH administration: pre-transfer group - administration by ambulance crew or physician-in-charge at the non-PPCI centre, 758 patients (57%); post transfer group - administration in the CathLab, 568 patients (43%). The time range between symptom onset (SO) and UFH administration (SO-UFH) was assessed and the 1-year mortality prediction was analysed by logistic regression. Initial IRA TIMI 2-3 flow was 30.3% in pre-transfer group vs. 21.2% in post-transfer group (p<0.001). A time-dependent association was found between SO-UFH and initial TIMI 2-3 in pre- vs. post-transfer groups [<120 min: 33.2% vs. 18%, p<0.001; 120-240 min: 29.2% vs. 22.8%, p=0.18; >240 min: 25% vs. 28%, p=0.57]. No differences in major bleeding were found between groups. UFH administration before transfer remained an independent predictor for initial TIMI 2-3 flow (OR 1.60 CI 95% 1.22 2.11, p=0.01) and for 1-year mortality (OR 0.51 CI 95% 0.29-0.91, p=0.02). CONCLUSIONS: Early UFH administration in STEMI patients transferred for PPCI results in higher IRA initial patency in a time-dependent manner and improves clinical outcomes. PMID- 26159241 TI - Inter-arm systolic blood pressure difference is a useful predictor for clinical outcome. PMID- 26159242 TI - The impact of initiating rivaroxaban versus low-molecular weight heparin plus warfarin in patients admitted to the hospital for venous thromboembolism. PMID- 26159243 TI - Interleukin-17 inhibition: An important target for attenuating myocardial ischemia and reperfusion injury. PMID- 26159244 TI - Vitamin D: A potential important therapeutic target for atrial fibrillation. PMID- 26159245 TI - Tinnitus preceding tachycardia and syncope. PMID- 26159246 TI - Risk of major cardiovascular events among incident dialysis patients: A Korean national population-based study. AB - BACKGROUND: Dialysis patients are at high risk for cardiovascular diseases, but until now there have been no detailed analyses of the incidences among Asian patients initiating dialysis. The aims of this study were to determine the incidence rates of major adverse cardiac and cerebrovascular events (MACCE) and to compare them between incident HD patients and PD patients. METHODS: We included all patients who had started dialysis between January 1, 2005 and December 31, 2008 in Korea, and analyzed 30,279 eligible patients [22,892 hemodialysis (HD) patients and 7387 peritoneal dialysis (PD) patients] by intention-to-treat. Median follow-up was 21.5 months. RESULTS: The crude incidence rates were as follows: MACCE, 182 per 1000 patient-years (PY); major adverse cardiac events (MACE), 138/1000 PY; all-cause mortality, 116/1000 PY; non fatal acute myocardial infarction (AMI), 18/1000 PY; target vessel revascularization (TVR), 17/1000 PY; and non-fatal stroke, 60/1000 PY. When comparing all baseline covariate-adjusted relative risks between HD and PD patients, HD is overall superior to PD in terms of MACCE. Further examined by each endpoint, all-cause mortality, non-fatal AMI, and TVR occurred significantly more frequently in patients on PD than in those on HD, whereas non-fatal hemorrhagic stroke occurred significantly more frequently in patients on HD than in those on PD. CONCLUSIONS: The incidence of MACCE may be different from Western dialysis patients. HD is overall superior to PD in terms of MACCE as an initial dialysis modality. Underlying mechanisms differentially affecting cardiovascular outcomes by dialysis modality remain to be further elucidated. PMID- 26159247 TI - Transcortical Transventricular Endoscopic Approach and Ommaya Reservoir Placement for Cystic Craniopharyngioma. AB - The treatment of craniopharyngioma is varied. It ranges from radical excision to direct radiotherapy. As the morbidity of excision is high, more conservative approaches are used. Placement of a catheter and reservoir is one such option for cystic craniopharyngiomas. The positioning of catheters has been performed by various means. A method of endoscopic reservoir catheter placement is described. Three children with ages ranging from 5 to 12 years presented with clinical features of raised intracranial pressure. They did not have vision impairment. Imaging showed a predominantly cystic craniopharyngioma extending into the third ventricle with hydrocephalus. All underwent precoronal burr hole, transcortical transventricular endoscopic biopsy of craniopharyngioma, and Ommaya reservoir placement. There were no complications. All children did well after surgery and did not require further cyst aspiration. PMID- 26159248 TI - Comparable survival for young rectal cancer patients, despite unfavourable morphology and more advanced-stage disease. AB - BACKGROUND: Young patients with rectal cancer tend to present with more advanced stage disease and unfavourable tumour morphology. The effects of these tumour characteristics on survival in this particular patient group are unclear. METHODS: Population-based data from the Netherlands Cancer Registry (NCR) were used. Data from patients diagnosed with rectal cancer between 1989 and 2010 were selected. Younger patients (? 40 years) were compared with middle-aged patients (41-70 years) with respect to disease stage, tumour characteristics, treatment and outcomes. Patients aged older than 70 years were excluded. Relative excess risk (RER) models were used to perform uni- and multivariate survival analyses. FINDINGS: A total of 37.056 patients were included (? 40 years n = 1.102). Compared with middle-aged patients, young patients were more likely to have stage III (33.8% versus 27.8%) and stage IV (24.3% versus 19.6%) disease (p < 0.001). Young patients also presented more frequently with mucinous tumours (10.8% versus 9.0%), signet cell carcinomas (2.6% versus 0.6%) and poorly differentiated tumours (16.6% versus 12.3%) (p = 0.001). The treatment of stage I-III patients did not differ between the two groups, except regarding adjuvant chemotherapy, which was more often given to young patients (24.3% versus 14.4%, p < 0.001). Young age was a prognostic factor for better survival in stage I-III patients (RER 0.82 CI 0.71-0.94). Adjuvant chemotherapy was associated with improved survival in stage I-III patients (RER 0.76, 95%CI 0.70-0.83). In an exploratory analysis, adjuvant chemotherapy in young stage III and pN1 patients was associated with improved survival. CONCLUDING STATEMENT: Young patients present with more advanced disease and have more unfavourable tumour characteristics compared with middle-aged patients. Despite these characteristics, survival rates are equal, and young age is a prognostic factor for better survival. Although the use of adjuvant chemotherapy is controversial, a positive correlation with survival was found in this study. PMID- 26159249 TI - Closure of a patent foramen ovale in patients with platypnoea-orthodeoxia: a rare and overlooked cause of dyspnoea and hypoxaemia. AB - OBJECTIVE: Platypnoea-orthodeoxia is a rare cause of dyspnoea and hypoxaemia induced by a change from supine to upright position resulting in veno-arterial shunting, usually through a patent foramen ovale. We aimed to describe our experience with closure of a patent foramen ovale in patients with platypnoea orthodeoxia, and to increase awareness of this diagnosis. DESIGN: Eight patients (mean age 63 +/- 12 years) were identified from hospital records between 2000 and 2013. RESULTS: The underlying diseases were aortic aneurism (n = 3), cardiac transplantation (n = 2), left ventricular dilatation (n = 1), pulmonary fibrosis (n = 1), and recurrent pleural/pericardial effusion (n = 1). At presentation, mean oxygen saturation was 81 +/- 8% in the upright position. All patients underwent transthoracic and transoesophageal echocardiography. Pulmonary pressures were normal at rest in all patients. A right-to-left shunt through a patent foramen was demonstrated after changing posture from supine to sitting. Closure of the patient foramen ovale was performed uncomplicated in all patients. Mean oxygen saturation post-procedure was 96 +/- 2%. All but one patient experienced marked symptom relief. CONCLUSION: The majority of patients with platypnoea-orthodeoxia can benefit from treatment of the underlying condition. In the present cohort, patients underwent uncomplicated catheter-based closure of the patient foramen ovale with subsequent improvement of oxygen saturation and symptom improvement. PMID- 26159250 TI - Marine n-3 PUFA protects hearts from I/R injury via restoration of mitochondrial function. AB - OBJECTIVES: Overwhelming evidence shows that dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) elicits protective effects on patients with cardiovascular disease. However, the detailed mechanisms underlying n-3 PUFA mediated cardioprotection are unknown, and examined in the present study. METHODS: We evaluated heart performances with Langendorff perfusion apparatus. Meanwhile, whole mitochondria were purified from non-perfused hearts for functional assessment, and lipid peroxidation level was measured as well. RESULTS: Compared with control groups, hearts from n-3 PUFA-supplemented rats showed improved functional recovery and reduced tissue injury following ischemia/reperfusion (I/R). Furthermore, the mitochondrial function of PUFA treated hearts was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity. In addition, thiobarbituric acid-reactive substance or TBARS assay revealed that lipid peroxidation product, malondialdehyde or MDA, in the mitochondria was significantly reduced by PUFA treatment. CONCLUSION: Taken together, our data indicate that marine n-3 PUFA could improve cardiac performance after I/R injury by restoring mitochondrial respiratory activities and attenuating lipid peroxidation. PMID- 26159251 TI - Catalyst-controlled divergence in cycloisomerisation reactions of N-propargyl-N vinyl sulfonamides: gold-catalysed synthesis of 2-sulfonylmethyl pyrroles and dihydropyridines. AB - Gold-catalysed, divergent synthesis of 2-sulfonylmethyl pyrroles and dihydropyridines from N-propargyl-N-vinyl sulfonamides has been achieved. Echavarren's gold(I) catalyst promoted the formation of pyrrole derivatives whereas the combination of PPh3AuCl and AgSbF6 afforded dihydropyridines. The aza enyne precursors for the cycloisomerisation reaction were prepared by a base mediated formal vinylic substitution reaction of 2-bromoallyl sulfones. PMID- 26159252 TI - Interaction Between IGF1 Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Chinese Children. AB - BACKGROUND/AIMS: IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' un-translated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman. Cell functional studies included real-time PCR, cell culture and transfection and luciferase assays. RESULTS: We found that rs6214 homozygous AA genotype and rs6218 homozygous CC genotype were significantly associated with increased risk of childhood ALL. In addition, rs6218 CC genotype was associated with increased level of IGF1 mRNA in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-miR-603 and hsa-miR-3941 in the 3'UTR of IGF1. CONCLUSION: Polymorphisms of rs6214 and rs6218 in the 3'UTR of IGF1 are associated with childhood ALL susceptibility, and the polymorphism of rs6218 is related with IGF1 expression at mRNA level. PMID- 26159253 TI - Anion exchangers with branched functional ion exchange layers of different hydrophilicity for ion chromatography. AB - Novel polystyrene-divinylbenzene (PS-DVB) based anion exchangers differing from each other in the structure of the branched functional ion exchange layer are prepared to investigate the role of linker and functional site on ion exchange selectivity. The proposed method of synthesis includes the obtaining of aminated PS-DVB particles by means of their acylation with following reductive amination with methylamine. Further modification of the obtained secondary aminogroups is provided by the alkylation with either 1,4-butanediol diglycidyl ether (1,4 BDDGE) or resorcinol diglycidyl ether (RDGE), which form the linkers of different hydrophobicity, and amination of terminal epoxide rings with trimethylamine (TMA), dimethylethanolamine (DMEA), methyldiethanolamine (MDEA) or triethanolamine (TEA). The variation of the structure and hydrophobicity of the linker and terminal quaternary ammonium sites in the functional layer allows the alteration of selectivity and separation efficiency of the obtained adsorbents. The ion exchange selectivity and separation efficiency of the anion exchangers are evaluated using the model mixtures of anions (F(-), HCOO(-), Cl(-), NO2(-), Br(-), NO3(-), HPO4(2-) and SO4(2-)) in potassium hydroxide eluents. The adsorbents show the decrease of selectivity with increasing the hydrophilicity of the terminal functional site. The anion exchangers having more flexible and hydrophilic 1,4-BDDGE linker provide smaller separation factors for most of the analytes as compared with RDGE-containing adsorbents with the same terminal ion exchange sites, but are characterized with higher column efficiencies and better peak symmetry for polarizable anions. In case of 1,4-BDDGE-modified anion exchangers of the particle size of 3.3MUm functionalized with DMEA and MDEA the calculated values of column efficiencies for polarizable NO3(-) and Br(-) are up to 49,000 and 53,000N/m, respectively, which is almost twice higher than the values obtained for the RDGE-containing analogues. PMID- 26159254 TI - Application of pH-sensitive magnetic nanoparticles microgel as a sorbent for the preconcentration of phenoxy acid herbicides in water samples. AB - Introducing new sorbents is an interesting and debatable issue in the field of sample preparation. In this study, for the first time, a pH-sensitive magnetic nanoparticles microgel, Fe3O4-SiO2-oly(4-vinylpyridine), was introduced as a new sorbent. The operating mechanism of this sorbent is based on changing the pH value of the sample and consequently the structure of this pH-sensitive microgel is changed. So that, at pH 6.0 the microgel was ready to accept and load the analytes (partial swelling), and when the pH was increased to 8.0, the microgel was closed and analytes were trapped inside the sorbent (deswelling). At pH 2.0 the microgel was opened and the analytes were released from the microgel (swelling). As the adsorption and desorption mechanism is based on changing the pH and only aqueous medium is used as the effluent solvent, this method is introduced as a green extraction method. The use of this microgel resulted in excellent figures of merit. The limits of quantitation and detection for herbicides were obtained within the range of 10-30 and 3-10 ng mL(-1), respectively. Finally, the proposed method was successfully applied to determine the concentration of phenoxy acid herbicides as hazardous materials in water samples. PMID- 26159255 TI - Biomechanical analysis of biphasic distribution of skull injury in falls from height. AB - Fall from height is one of the most common ways of suicide in Korea. Skull fractures are typically accompanied with these cases, but several autopsy cases show absence of skull fracture even with serious body injuries including sternal and vertebral fracture. The mechanism of this pattern of injury can be explained by impact of facial part on chest or abdomen when the back of the body touches the ground first. We tried to figure out the relevance of this pattern of injury to the height of fall using a computer simulation tool (MADYMO 7.5). For this experiment, a condition of initial pose was limited to leaning forward. The simulation showed that when the body rotated forward, the body parts which got injured by the ground depended on the height of fall. For relatively lower height, head got injured, but as the height was set higher, the point of first impact area changed to the back, hip and then legs. When the body struck first around hip area on supine position, the impact made forceful flexion of lumbar, thoracic and cervical vertebrae, leading to folding the body in two, which resulted in collision between the part of face and the anterior part of body. Through the current investigation, it was explained that the biphasic distribution of the number of head injury cases versus the height distribution was attributed to the forward rotation of the body during the fall. PMID- 26159256 TI - Homicidal assault to the neck with subsequent simulation of self-hanging. AB - When a body is found in suspended position, not only suicidal hanging has to be considered but also an accident or homicide. These alternatives and the criteria to be applied for their differentiation were already extensively discussed in the old medico-legal literature. Nevertheless, it is still a challenge for detectives and forensic experts to prove a homicidal assault when a suspended body is found. In the presented case, the findings collected at the scene and during autopsy seemed to be consistent with the assumption of suicide at first and the case has only been elucidated by supplementary inquiries and a secondary evaluation of the photos taken at the scene and during the autopsy. The victim, a 47-year-old woman, had been manually strangled in her flat. Subsequently, the perpetrator took her up to the attic and tried to hang her in order to simulate suicide. PMID- 26159257 TI - Incipient cytotoxicity: A time-independent measure of cytotoxic potency in vitro. AB - Time is an important determinant of toxicity but largely ignored in in vitro toxicity assays where exposure times chosen are rather arbitrary. To investigate the impact of time on the cytotoxic potency of chemicals in vitro, the concentration dependent cytotoxic action of selected chemicals (surfactants, metals, oxidative stressors, a mitochondrial poison) was determined after various exposure times (1-72 h) in cultures of Balb/c 3T3 cells. Time affected the cytotoxic potency as well as the cytotoxic efficacy. The median cytotoxic concentrations, EC50, decreased and in most cases approached an "incipient" value, EC50,infinity, within 72 h. Cytotoxicity due to mitochondrial insult occurred after a threshold time which was dependent on the medium glucose concentration. Within the chemicals studied the extent of potency change with time ranged from 3- to >1000-fold and the "time to incipient cytotoxicity", tic, from 4 to >72 h. Hence, also the relative cytotoxic potencies depend on exposure time. Ignoring this may lead to severe bias in toxicological hazard and risk assessment. Therefore it is recommended to determine the incipient cytotoxic potency of chemical compounds, represented by, e.g., the incipient median effect (EC50,infinity), no effect (NECinfinity) or lowest effect concentrations (LECinfinity) instead of measures obtained after arbitrary exposure times. If this is not possible, the 72 h-potency measurements appear to be useful surrogates. These time-independent incipient potency values can be reasonably compared between substances, endpoints, cells and biological test systems and may serve to define points of departure for quantitative in vitro-in vivo extrapolations. PMID- 26159258 TI - The Challenge of Drug-Induced Liver Injury (DILI) / Challenges and Management of Liver Cirrhosis. Preface. PMID- 26159259 TI - Drug-Induced Liver Injury Is a Major Risk for New Drugs. AB - Drug-induced liver injury (DILI), a relatively rare condition, is nevertheless a major reason for not approving a drug in development or for removing one already marketed. With a specific diagnostic biomarker lacking, finding elevated serum enzyme [alanine aminotransferase (ALT), aspartate aminotransferase and alkaline phosphatase] activities remains an initial signal for incipient liver injury. Enzyme elevations alone may not be harmful, but if caused by a drug and followed by jaundice (called 'Hy's law') there is a high possibility of serious DILI. In 1997 several drugs were approved by the Food and Drug Administration (FDA) of the USA that were later withdrawn from the market for serious liver toxicity. New drugs in development are now required to be monitored for liver injury, and the data is to be considered in the approval decision. A program called e-DISH (evaluation of drug-induced serious hepatotoxicity) was introduced in 2004 to aid medical reviewers to select from all subjects studied those few who show nontrivial liver injury and estimate the most likely cause. The threshold of enzyme elevation comprising a warning for possibly serious DILI is uncertain, although generally accepted as 3-5 times the 'upper limit of normal'. The new direct-acting antiviral agents for treating chronic hepatitis C virus, which often lead to a reduction of elevated ALTs, mandate that a later increase without viral breakthrough be compared to the new on-treatment level of values. The drug may be discontinued or interrupted for evaluation to exclude other possible causes of liver injury. The FDA has approved no drug since 1997 that has been withdrawn later because of serious hepatotoxicity. PMID- 26159261 TI - How to Diagnose and Exclude Drug-Induced Liver Injury. AB - The diagnosis of drug-induced liver injury (DILI) is largely a diagnosis of exclusion because, with the possible exception of protein:drug adducts in paracetamol overdose, there are no laboratory, biopsy or imaging tests that alone are capable of establishing an unequivocal diagnosis of DILI. However, it is increasingly appreciated that drugs that cause DILI typically have characteristic clinical presentations or 'signatures' that can be very useful in the diagnosis of DILI. Indeed, knowing a drug's DILI signature (or sometimes signatures) and the incidence rate of DILI during treatment with that drug are perhaps the most useful pieces of historical information in arriving at the diagnosis of DILI. Components of the signature include the typical latency from the onset of treatment, whether there are extrahepatic manifestations, whether the injury is hepatocellular, cholestatic or mixed, and sometimes characteristic features on biopsy or serological testing (e.g. liver autoantibodies). A major advance has been the establishment of the LiverTox website (http://livertox.nih.gov/) which provides open access to standardized entries for over 600 different drugs, including the characteristic clinical presentations of DILI when known. LiverTox will also calculate the causality score for individual cases using the RUCAM instrument and case-specific data entered by the site user. However, the problem with standard diagnostic instruments such as the RUCAM is that DILI signatures are not incorporated into the scoring system. The person entering data must therefore subjectively weigh the RUCAM score with the characteristic DILI signature(s) of the drug to arrive at a diagnosis. In the future, it should be possible to construct improved diagnostic instruments that objectively incorporate DILI signatures, data-based estimates of the incidence rates of DILI from each implicated drug, and perhaps genetic variants associated with the risk of DILI. PMID- 26159260 TI - Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients. AB - BACKGROUND: Drug-induced liver injury is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure at therapeutic doses in a very limited number of patients (<1:10,000). This idiosyncratic drug-induced liver injury, which is currently not predictable in preclinical safety studies, appears to depend on individual susceptibility and the inability to adapt to the cellular stress caused by a particular drug. In striking contrast to idiosyncratic drug-induced liver injury, drugs with dose dependent hepatotoxicity are mostly detected during preclinical studies and do not reach the market. One notable exception is acetaminophen (APAP, paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and acute liver failure after intentional and unintentional overdoses. Key Messages: APAP overdose is responsible for more acute liver failure cases in the USA or UK than all other etiologies combined. Since APAP overdose in the mouse represents a model for the human pathophysiology, substantial progress has been made during the last decade in understanding the mechanisms of cell death, liver injury and recovery. More recently, emerging evidence based on mechanistic biomarker analysis in patients and studies of cell death in human hepatocytes suggests that most of the mechanisms discovered in mice also apply to patients. The rapid development of N-acetylcysteine as an antidote against APAP overdose was based on the early understanding of APAP toxicity in mice. However, despite the efficacy of N-acetylcysteine in patients who present early after APAP overdose, there is a need to develop intervention strategies for late-presenting patients. CONCLUSIONS: The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent acute liver failure, and also to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure with poor outcome. PMID- 26159262 TI - Preventing Drug-Induced Liver Injury: How Useful Are Animal Models? AB - Drug-induced liver injury (DILI) is the most common organ toxicity encountered in regulatory animal toxicology studies required prior to the clinical development of new drug candidates. Very few reports have evaluated the value of these studies for predicting DILI in humans. Indeed, compounds inducing liver toxicity in regulatory toxicology studies are not always correlated with a risk of DILI in humans. Conversely, compounds associated with the occurrence of DILI in phase 3 studies or after market release are often tested negative in regulatory toxicology studies. Idiosyncratic DILI is a rare event that is precipitated in an individual by the simultaneous occurrence of several critical factors. These factors may relate to the host (e.g. human leukocyte antigen polymorphism, inflammation), the drug (e.g. reactive metabolites) or the environment (e.g. diet/microbiota). This type of toxicity therefore cannot be detected in conventional animal toxicology studies. Several animal models have recently been proposed for the identification of drugs with the potential to cause idiosyncratic DILI: rats treated with lipopolysaccharide, Sod2(+/-) mice, panels of inbred mouse strains or chimeric mice with humanized livers. These models are not suitable for use in the prospective screening of new drug candidates. Humans therefore constitute the best model for predicting and assessing idiopathic DILI. PMID- 26159263 TI - Drug-Induced Liver Injury and Individual Cell Models. AB - Drug-induced liver injury (DILI) is the most common cause of acute liver failure and accounts for the majority of regulatory actions on drugs. Furthermore, DILI is a relevant cause for project terminations in pharmaceutical development. The idiosyncratic form of DILI is especially a threat in late clinical development phases and postmarketing, respectively. Even the occurrence of only a few idiosyncratic DILI cases in late clinical development or postmarketing may suffice to terminate or withdraw an otherwise promising therapy. Despite advances in preclinical assessment of dose-dependent toxicity, idiosyncratic DILI is still a big challenge for in vitro research: it not only requires individualized models but also a huge number of tests. We have developed and investigated MetaHeps(r), a technology involving hepatocyte-like cells generated from peripheral monocytes without genetic modifications. These cells exhibit several hepatocyte-like characteristics and show donor-specific activities of drug-metabolizing enzymes. With MetaHeps we have performed in vitro investigations in patients with DILI suspicion. By investigating MetaHeps derived from DILI patients we could show increased in vitro susceptibility to the drugs involved in the individual patients. MetaHeps testing could also rule out DILI and help to identify other causes of acute liver injury. Moreover, MetaHeps identified the causative agent in polymedicated patients. In conclusion, in vitro research of idiosyncratic DILI requires individual cell models which produce results comparable to the clinical situation. We suggest the MetaHeps technology as a novel tool to cope with these challenges of DILI. PMID- 26159264 TI - Pathophysiology of Liver Fibrosis. AB - Progressive accumulation of fibrillar extracellular matrix (ECM) in the liver is the consequence of reiterated liver tissue damage due to infective (mostly hepatitis B and C viruses), toxic/drug-induced, metabolic and autoimmune causes, and the relative chronic activation of the wound-healing reaction. The process may result in clinically evident liver cirrhosis and hepatic failure. Although cirrhosis is the common result of progressive fibrogenesis, there are distinct patterns of fibrotic development related to the underlying disorders causing the fibrosis. These different patterns of fibrogenic evolution are related to different factors and particularly: (1) the topographic localization of tissue damage, (2) the relative concentration of profibrogenic factors and (3) the prevalent profibrogenic mechanism(s). The mechanisms responsible for the fibrogenic evolution of chronic liver diseases can be summarized in three main groups: chronic activation of the wound-healing reaction, oxidative stress related molecular mechanisms, and the derangement of the so-called 'epithelial mesenchymal' interaction leading to the generation of reactive cholangiocytes and peribiliary fibrosis. Most of the knowledge on the cell and molecular biology of hepatic fibrosis derives from in vitro studies employing culture of activated hepatic stellate cells isolated from rat, mouse or human liver. It is now evident that other ECM-producing cells, i.e. fibroblasts and myofibroblasts of the portal tract and circulating 'fibrocytes', are likely to contribute to liver fibrosis. More recently, the attention is progressively shifting to the profibrotic microenvironment of the liver with increasing interest for the role of immune cells and specific subsets of macrophages regulating the progression or the regression of fibrosis, the role of intestinal microbiota and the influence of tissue stiffness. Other major areas of development include the role of tissue hypoxia and the establishment of an anaerobic proinflammatory environment and the influence of epigenetic modification in conditioning the progression of fibrosis. PMID- 26159265 TI - Noninvasive Assessment of Liver Fibrosis. AB - BACKGROUND: The prognosis and management of chronic liver diseases greatly depend on the amount and progression of liver fibrosis with the risk of developing cirrhosis. Liver biopsy, traditionally considered as the reference standard for the staging of fibrosis, has been challenged over the past decade by the development of novel noninvasive methodologies. Key Messages: Noninvasive methods rely on two different but complementary approaches: a 'biological' approach based on the dosage serum biomarkers, and a 'physical' approach based on the measurement of liver stiffness using transient elastography (TE). There are two clinically relevant endpoints for the staging of liver fibrosis: (1) significant fibrosis (indication for antiviral treatment in viral hepatitis B and C), and (2) cirrhosis (indication for screening of esophageal varices and hepatocellular carcinoma). TE (FibroScan(r)), FibroTest(r) and APRI have been the most extensively studied and validated methods, mainly in chronic hepatitis C. Combining two unrelated methods, such as TE and biomarkers, is an attractive approach that increases diagnostic performance and limits the drawback of both methodologies. TE appears to be an excellent tool for the early detection of cirrhosis with likely prognostic value in this setting. Thus far, however, it cannot replace upper endoscopy for screening of esophageal varices. The main limitation of TE in clinical practice is the impossibility of obtaining reliable liver stiffness measurements in around 20% of cases, mainly comprising obese patients. CONCLUSION: An increasing number of reliable noninvasive methods are now available that are widely used in clinical practice, mostly in viral hepatitis, resulting in a significant decrease in the need for liver biopsy. PMID- 26159266 TI - Hepatic Fibrosis: Emerging Therapies. AB - There has been tremendous progress made in understanding the pathogenesis of hepatic fibrosis, which has created new opportunities for the treatment of this condition. Clinical evidence of fibrosis reversibility has established that the liver has the capacity to resorb scar tissue, and future therapies will be based in part on this insight. Additionally, the paradigm of hepatic stellate cell activation provides an important template for defining targets of antifibrotic therapy. Opportunities abound to accelerate drug approvals once biomarkers are improved and endpoints of clinical trials are better defined. Overall, there is heartening evidence that fibrosis is a tractable consequence of chronic liver disease that will be amenable to therapy even when the underlying disease has not been cured. PMID- 26159267 TI - Pathophysiology and a Rational Basis of Therapy. AB - Portal hypertension is a common complication of chronic liver disease. Its relevance comes from the fact that it determines most complications leading to death or liver transplantation in patients with cirrhosis of the liver: bleeding from esophageal or gastric varices, ascites and renal dysfunction, sepsis and hepatic encephalopathy. Portal hypertension results from increased resistance to portal blood flow through the cirrhotic liver. This is caused by two mechanisms: (1) distortion of the liver vascular architecture due to the liver disease causing structural abnormalities (nodule formation, remodeling of liver sinusoids, fibrosis, angiogenesis and vascular occlusion), and (2) increased hepatic vascular tone due to sinusoidal endothelial dysfunction, which results in a defective production of endogenous vasodilators, mainly nitric oxide (NO), and increased production of vasoconstrictors (thromboxane A2, cysteinyl leukotrienes, angiotensin II, endothelins and an activated adrenergic system). Hepatic endothelial dysfunction occurs early in the course of chronic liver disease as a consequence of inflammation and oxidative stress, and determines loss of the normal phenotype of liver sinusoidal endothelial cells (LSECs) that become proliferative, prothrombotic, proinflammatory and vasoconstrictor. The cross-talk between LSECs and hepatic stellate cells (HSCs) induces activation of the latter, which in turn proliferate, migrate and increase collagen deposition around the sinusoids, contributing to fibrogenesis, architectural disruption and angiogenesis, which further increase the hepatic vascular resistance and worsen liver failure by interfering with the blood perfusion of the liver parenchyma. An additional factor further worsening portal hypertension is an increased blood flow through the portal system due to splanchnic vasodilatation. This is an adaptive response to decreased effective hepatocyte perfusion, and is maximal once portal pressure has increased sufficiently to promote the development of intrahepatic shunts and portal-systemic collaterals, including varices, through which portal blood flow bypasses the liver. In human portal hypertension collateralization and hyperdynamic circulation start at a portal pressure gradient >10 mm Hg. Rational therapy for portal hypertension aims at correcting these pathophysiological abnormalities: liver injury, fibrogenesis, increased hepatic vascular tone and splanchnic vasodilatation. Continuing liver injury may be counteracted specifically by etiological treatments (the best example being the direct-acting antivirals for hepatitis C viral infection), while architectural disruption and fibrosis can be ameliorated by a variety of antifibrotic drugs and antiangiogenic strategies. Several drugs in this category are currently under investigation in phase II-III randomized controlled trials. Sinusoidal endothelial dysfunction is ameliorated by statins as well as by other drugs increasing NO availability. It is of note that simvastatin has already been proven to be clinically effective in two randomized controlled trials. Splanchnic hyperemia can be counteracted by nonselective beta-blockers (NSBBs), vasopressin analogs and somatostatin analogs, drugs that until recently were the only available treatments for portal hypertension, but that are not very effective in the initial stages of cirrhosis. There is experimental and clinical evidence indicating that a more effective reduction of portal pressure is obtained by combining agents acting on these different pathways. It is likely that the treatment of portal hypertension will evolve to use etiological treatments together with antifibrotic agents and/or drugs improving sinusoidal endothelial function in the initial stages of cirrhosis (preprimary prophylaxis), while NSBBs will be added in advanced stages of the disease. PMID- 26159268 TI - Clinical Evaluation and Prognosis. AB - BACKGROUND: Liver cirrhosis is no longer considered a homogeneous disease, with two different phases now identified: 'compensated' and 'decompensated' cirrhosis, in which complications of cirrhosis characterize the latter. Within each phase, different stages and predictors should be recognized in order to correctly stratify the prognosis and individualize possible therapeutic options. Key Messages: In compensated cirrhosis the presence of clinically significant portal hypertension [CSPH = hepatic venous pressure gradient (HVPG) >=10 mm Hg] constitutes the most important independent predictor of several relevant clinical endpoints (formation of esophageal varices; first clinical decompensation). An optimal HVPG response to medical therapy of portal hypertension (HVPG reduction <12 mm Hg or >=20% vs. the pretreatment value, responders) has been consistently linked to a decrease in the risk of variceal bleeding both in primary and secondary prophylaxis, and to a decrease in the risk of presenting other clinical decompensating events. Furthermore, in patients undergoing secondary prophylaxis of variceal bleeding, being an HVPG responder is associated with an improved survival. HVPG also maintains an independent prognostic value in patients with decompensated cirrhosis. Noninvasive alternatives to HVPG for the prediction of CSPH have been investigated; liver stiffness by transient elastography and the combination of liver stiffness, spleen size by ultrasound and platelet count are currently the best methods to noninvasively diagnose CSPH, with an accuracy of about 90%. Additional factors modulate prognosis in cirrhosis. Liver function (albumin, bilirubin, INR) is independently associated with prognosis both in compensated and decompensated cirrhosis, and in the latter phase renal function also plays a central role. Among clinical cofactors, obesity and diabetes are emerging as variables increasing the risk of progression to decompensation and death in cirrhosis. CONCLUSIONS: Prognostic stratification in patients with cirrhosis should take into account a complex interplay of several clinical, hemodynamic and biological variables. The present review summarizes the existing evidence regarding prognostic factors in cirrhosis, with particular emphasis on compensated cirrhosis. PMID- 26159269 TI - Therapies: Drugs, Scopes and Transjugular Intrahepatic Portosystemic Shunt--When and How? AB - Variceal bleeding is the most serious complication of portal hypertension. All cirrhotic patients should be screened endoscopically for varices which are present in about 30% of compensated and 60% of decompensated patients at diagnosis. In patients without varices, endoscopy surveillance should be continued every 2 years. Patients with high-risk varices (moderate or large in size, or with red color signs, or in Child-Pugh C patients) should be treated with a nonselective beta-blocker to prevent bleeding (propranolol, nadolol or carvedilol). Endoscopic banding ligation is also effective for the prevention of first bleeding, and it is the first choice in patients with contraindications or intolerance to beta-blockers. Acute variceal hemorrhage still has a high mortality rate (around 15%) and requires intensive care management and conservative blood transfusion policy. Treatment is based on the combined use of vasoactive drugs, endoscopic band ligation and prophylactic antibiotics. Failures are best managed by transjugular intrahepatic portosystemic shunt (TIPS). Balloon tamponade or specifically designed covered esophageal stents can be used as a bridge to definitive therapy in unstable patients. Early, preemptive TIPS might be the first choice in patients at high risk of failure (Child-Pugh B with active bleeding or Child-Pugh C up to 13 points). Patients surviving a variceal bleeding are at high risk of rebleeding. A combination of beta-blockers and endoscopic band ligation is the most effective therapeutic approach. Preliminary data suggest that the addition of simvastatin increases survival in these patients. PMID- 26159270 TI - Challenges and Management of Liver Cirrhosis: Pathophysiology of Renal Dysfunction in Cirrhosis. AB - Kidney dysfunction is a common complication of patients with advanced cirrhosis and is associated with poor prognosis. Patients with advanced cirrhosis show circulatory dysfunction characterized by reduced systemic vascular resistance due to splanchnic arterial vasodilation, which is caused by portal hypertension. The progressive reduction in systemic vascular resistance leads to effective arterial hypovolemia. In order to maintain arterial pressure within normal limits in this setting, there is activation of systemic vasoconstrictor systems, including the renin-angiotensin-aldosterone system, sympathetic nervous system and, in late stages, nonosmotic hypersecretion of vasopressin. Although these systems have positive effects in maintaining arterial pressure, they have a negative influence on kidney function, leading to the retention of sodium and solute-free water, and in late stages of the disease an intense kidney vasoconstriction develops, leading to decrease of the glomerular filtration rate and the development of hepatorenal syndrome (HRS). Moreover, bacterial translocation and the existence of a systemic inflammatory state in patients with advanced cirrhosis may play a role in the impairment of circulatory function. HRS is a unique cause of kidney failure of functional origin that develops in patients with cirrhosis. However, besides HRS, patients with cirrhosis may develop kidney failure due to other causes, including bacterial infections, prerenal kidney failure, shock, use of nephrotoxic drugs or intrinsic kidney diseases. Considering the existence of circulatory dysfunction and some degree of kidney vasoconstriction, patients with advanced cirrhosis have fragile kidney function and are susceptible to easily developing kidney failure associated with other complications of the disease, particularly bacterial infections and gastrointestinal bleeding. PMID- 26159271 TI - Definition and Diagnosis of Acute Kidney Injury in Cirrhosis. AB - BACKGROUND: Acute kidney injury (AKI) is a common complication of advanced cirrhosis. Type 1 hepatorenal syndrome is the best-known and most severe form of AKI, and it has a precise definition and a set of specific diagnostic criteria. More recently, it has become recognized that milder degrees of renal dysfunction also have a negative impact on patient outcome in various patient populations. Key Messages: Several definitions and criteria for staging the severity of AKI have been proposed, including the RIFLE (Risk, Injury, Failure, Loss of Function and End-Stage Renal Disease) group, the Acute Kidney Injury Network (AKIN), and the Kidney Disease: Improving Global Outcome (KDIGO) group. All of them incorporate some changes of serum creatinine and urine output in the definition and staging of AKI. The hepatology community has mostly embraced the AKIN diagnostic and staging criteria and has applied them in the prognostication of patients with advanced cirrhosis. However, the AKIN criteria have not been strictly applied in all studies on cirrhosis. This is partly related to the fact that changes in urine output are difficult to assess in advanced cirrhosis, and partly related to the difficulty in defining the baseline serum creatinine from which the change in serum creatinine is calculated. This has led to some confusion in the interpretation of results of the various studies on AKI in cirrhosis. More recently, some investigators have suggested incorporating the AKIN criteria with setting a lower limit of serum creatinine of 1.5 mg/dl in determining the diagnosis and prognosis of AKI in cirrhosis. CONCLUSIONS: This is an ongoing debate as to how best to define AKI in cirrhosis. In the near future there should be prospective clinical trials that will clarify which diagnostic and staging criteria of AKI will best serve the cirrhotic population. PMID- 26159272 TI - The Treatment of Hepatorenal Syndrome. AB - Hepatorenal syndrome (HRS) is a severe complication that often occurs in patients with cirrhosis and ascites. HRS is a functional renal failure that develops mainly as a consequence of a severe cardiovascular dysfunction which is characterized by an extreme splanchnic arterial vasodilation and a reduction of cardiac output. HRS may develop in two clinical types: as an acute and rapidly progressive renal failure (AKI-HRS) or as chronic and not progressive renal failure (CKD-HRS). Several small studies and some randomized control studies have been published on the use of terlipressin plus albumin in the treatment of HRS, mainly on AKI-HRS. Terlipressin plus albumin was shown to improve renal function in almost 35-45% of patients with AKI-HRS, as well as to improve short-term survival in these patients. Terlipressin was most commonly used by intravenous boluses moving from an initial dose of 0.5-1 mg every 4 h to 3 mg every 4 h in the case of a nonresponse. In other studies, terlipressin was also given by continuous intravenous infusion. Thus, the best way to administer terlipressin in the treatment of HRS has not yet been defined. alpha-Adrenergic drugs, such as intravenous norepinephrine or oral midodrine plus subcutaneous octreotide, administered with albumin have also been used in the treatment of AKI-HRS, with promising results. However, we need further studies in order to define whether they can represent a real therapeutic alternative. In conclusion, available data are sufficient to state that the use of terlipressin plus albumin has really changed the management of HRS. Nevertheless, some crucial unsolved issues still exist, in particular: (a) how to predict nonresponse to treatment, (b) how to manage nonresponse to treatment and (c) how to consider the response in those patients who are candidates for liver transplant in the priority allocation process. PMID- 26159273 TI - The Clinical Relevance of Minimal Hepatic Encephalopathy--A Critical Look. AB - Minimal hepatic encephalopathy (mHE) is diagnosed in patients with severe liver disease but no clinical symptoms of encephalopathy if either neuropsychological or neurophysiological tests indicate cerebral dysfunction and other possible causes of brain dysfunction have been excluded. mHE is characterized by deficits in attention, visuospatial orientation, visuoconstructive abilities and motor function. Accordingly, mHE can be expected to interfere with a subject's working ability, especially in those occupations that require handiwork, and driving ability. Indeed, about 60% of blue-collar workers with mHE have been shown to be assessed as unfit for work compared to only 20% of white-collar workers, and about 50% of patients with mHE have been judged unfit to drive a car in several studies. mHE interferes with a patient's quality of life and is associated with an increased risk of developing overt HE as well as increased mortality. Whether mHE is of importance for cognitive function after liver transplantation has still to be clarified. PMID- 26159274 TI - Diagnosis and Treatment of Low-Grade Hepatic Encephalopathy. AB - Minimal hepatic encephalopathy (mHE) is common among patients with cirrhotic liver disease and causes significant morbidity and mortality. It may present as cognitive impairment, behavioural changes and, less frequently, with neurological symptoms which make diagnosis of the disease challenging. A history of falls and accidents may also be suggestive of mHE. Diagnosis primarily relies on at least two positive psychometric tests of which the psychometric hepatic encephalopathy score (PHES) is essential. Alternatively, PHES and an electroencephalogram may be used to establish a diagnosis. Biochemical markers of encephalopathy currently have no role in the diagnosis of mHE. Treatment is not always advocated for a diagnosis of mHE but is dependent on the degree of impairment caused by the symptoms. After treatment of other metabolic abnormalities and co-morbidities associated with cirrhosis, more specific treatment for mHE largely relies on therapies used to lower ammonia levels. Laxatives and rifaximin are commonly used in treatment and work through decreasing ammonia absorption from the gut. Other therapies, such as BCAA, LOLA, L-carnitine and phenylbutyrate, modify responses to ammonia as well as enhancing metabolism and excretion. mHE resulting from spontaneous portosystemic shunts or transhepatic intraportal systemic shunts may require ablation or reduction of the shunt. Early detection and appropriate treatment of mHE is important to prevent significant cognitive impairments and progression to overt HE. PMID- 26159275 TI - Infection as a Trigger for Portal Hypertension. AB - BACKGROUND: Microbial infections are a relevant problem for patients with liver cirrhosis. Different types of bacteria are responsible for different kinds of infections: Escherichia coli and Klebsiella pneumoniae are frequently observed in spontaneous bacterial peritonitis or urinary tract infections, and Streptococcus pneumoniae and Mycoplasma pneumoniae in pulmonary infections. Mortality is up to 4-fold higher in infected patients with liver cirrhosis than in patients without infections. Key Messages: Infections in patients with liver cirrhosis are due to three major reasons: bacterial translocation, immune deficiency and an increased incidence of systemic infections. Nonparenchymal liver cells like Kupffer cells, sinusoidal endothelial cells and hepatic stellate cells are the first liver cells to come into contact with microbial products when systemic infection or bacterial translocation occurs. Kupffer cell (KC) activation by Toll-like receptor (TLR) agonists and endothelial sinusoidal dysfunction have been shown to be important mechanisms increasing portal pressure following intraperitoneal lipopolysaccharide pretreatment in cirrhotic rat livers. Reduced intrahepatic vasodilation and increased intrahepatic vasoconstriction are the relevant pathophysiological pathways. Thromboxane A2 and leukotriene (LT) C4/D4 have been identified as important vasoconstrictors. Accordingly, treatment with montelukast to inhibit the cysteinyl-LT1 receptor reduced portal pressure in cirrhotic rat livers. Clinical studies have demonstrated that activation of KCs, estimated by the amount of soluble CD163 in the blood, correlates with the risk for variceal bleeding. Additionally, intestinal decontamination with rifaximin in patients with alcohol-associated liver cirrhosis reduced the portal pressure and the risk for variceal bleeding. CONCLUSIONS: TLR activation of nonparenchymal liver cells by pathogens results in portal hypertension. This might explain the pathophysiologic correlation between microbial infections and portal hypertension in patients with liver cirrhosis. These findings are the basis for both better risk stratifying and new treatment options, such as specific inhibition of TLR for patients with liver cirrhosis and portal hypertension. PMID- 26159276 TI - Role of Infections in Acute-on-Chronic Liver Failure. AB - Patients with cirrhosis are prone to developing bacterial infections. Moreover, bacterial infection is the most common identifiable trigger of acute-on-chronic liver failure (ACLF), which is characterized by organ failures and a high risk of death. There is evidence of an excessive immune response of the host as a major mechanism leading to the development of organ failures in patients with cirrhosis. However, a role for direct tissue damage caused by bacterial toxins and virulence factors cannot be excluded. Failed tolerance mechanisms may also contribute to organ failures, although the involved mechanisms are unclear. A proportion of patients with infection-related ACLF have a prolonged stay in the intensive care unit. These patients have immune suppression, increased risk of superinfection and poor outcome. Immune suppression might be a consequence of the first infection episode that has led patients to be admitted to hospital. PMID- 26159277 TI - Treatment of Spontaneous Bacterial Peritonitis. AB - Spontaneous bacterial peritonitis (SBP) is an infection of patients with cirrhosis and ascites. This peculiarity is due to the frequent intestinal translocation that allows bacteria to cross the intestinal barrier, colonizing the ascitic fluid. In cirrhosis, SBP is inferior only to urinary tract infections. It is prevalently sustained by Gram-negative bacteria such as Escherichia coli and Klebsiella. Risk factors for developing SBP are advanced age, refractory ascites, variceal bleeding, renal failure, low albumin levels (below 2.5 g/ml), bilirubin over 4 mg/dl, Child-Pugh class C and a previous diagnosis of SBP. Thus, this is an indication for a long-term antibiotic prophylaxis with norfloxacin. Renal failure - especially the hepatorenal syndrome - complicates SBP in about 20% of cases independently of the efficacy of the antibiotic therapy. The mortality of these patients is about 90%. Infusion of albumin significantly reduces the incidence of hepatorenal syndrome and consequently the risk of death. Long-term quinolonic prophylaxis as well as increased antibiotic therapies are causing the emergence of multidrug-resistant agents as frequent causes of SBP. In such cases, the antibiotic sensitivity to quinolones is low, and European recommendations suggest a second-line antibiotic therapy, including meropenem or piperacillin plus tazobactam. Collection of blood, urine and ascitic fluid for cultures is important for bacterial recognition, possibly before starting an empirical antibiotic therapy. Indeed, the probability of positive cultures rapidly vanishes when they are performed during already implemented antibiotic administration. It is important to know that a failure of the first-line therapy is associated with an increased probability of death. PMID- 26159278 TI - Molecular Profiling and Research of Therapeutic Targets. AB - The heterogeneous nature of hepatocellular carcinoma (HCC) poses a challenge to effective therapy. Significant strides have been made in molecular profiling. Telomerase promoter mutations are now known to represent early events in linear carcinogenesis. However, the translation of these advances into clinical practice has been limited. Although further work is needed to extrapolate genetic information to patient care, progress has been made in using genetics and stratification for HCC therapy. Targeted therapies for patients with c-MET overexpression, VEGF-A amplification and Wnt beta-catenin-driven tumors offer promise. PMID- 26159279 TI - Systemic Treatment: Expecting Further Success. AB - From its approval in 2008, sorafenib is the recommended treatment option for advanced-stage patients and its safety and efficacy has been confirmed by several studies. However, its mechanism of action is not completely understood and many efforts have been dedicated to investigating possible treatment response predictors. Dermatological adverse events occurring within the first 2 months of treatment are predictors of longer survival, while the same role for hypertension and diarrhea still needs a prospective confirmation. This association is opposite to the strategy of starting at a low dose as it may imply suboptimal drug exposure. In case of radiological progression, the appearance of new extrahepatic metastasis or vascular invasion significantly worsens life expectancy if compared to other patterns of progression. To date no genetic or biologic marker is available to predict response, even if some encouraging results have been reported by the study of polymorphism of VEGF and its receptor. Currently, data are conflicting about the possible predictive role of alpha-fetoprotein. Due to failure or the progression of therapies for earlier evolutionary stages (BCLC B) some patients in such a clinical profile may be treated with sorafenib. Indeed, almost 50% of the sorafenib-treated patients belong to this class. Patients with severely decompensated liver disease (jaundice, ascites in need of intense diuretic therapy/paracentesis) may not benefit from treatment. The use of sorafenib in the waiting list for liver transplantation is controversial, while its use at an advanced age requires careful evaluation of existing comorbidities that may increase the risk of adverse events. Many strides have been made in the field of hepatocellular carcinoma systemic therapy, and many remain to be realized. Considering the disappointing results of the trials conducted on new agents, a more dynamic interpretation of events together with the development of new strategies is key to enriching new and hopefully more successful trials. PMID- 26159280 TI - Challenges and Management of Liver Cirrhosis: Practical Issues in the Therapy of Patients with Cirrhosis due to NAFLD and NASH. AB - Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH. PMID- 26159281 TI - Antiviral Therapy in Hepatitis B Virus-Associated Liver Cirrhosis. AB - BACKGROUND: Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of liver cirrhosis and hepatocellular carcinoma (HCC). Key Messages: In patients with advanced liver fibrosis or liver cirrhosis, antiviral therapy is mandatory to slow down, halt or reverse disease progression and possibly reduce the risk of HCC development. As in patients without advanced fibrosis, PEG-interferon and nucleoside/nucleotide analogues (NUCs) are available for antiviral therapy. NUC therapy should be performed indefinitely as the rates of HBs-Ag loss are low. Entecavir or tenofovir should be preferred due to their strong antiviral potency and their high barrier to resistance. PEG-interferon therapy can be administered to patients with compensated liver disease but should not be offered to patients with signs of hepatic decompensation. CONCLUSIONS: Antiviral therapy in chronic HBV infection can reduce liver fibrosis and even revert overt cirrhosis. Whether it also reduces the risk of HCC development in cirrhotic patients remains elusive and might vary in different countries and ethnicities. PMID- 26159282 TI - Antiviral Therapy in Patients with Hepatitis C Virus-Induced Cirrhosis. AB - BACKGROUND: Opportunities to treat infection with hepatitis C virus (HCV) are evolving rapidly. From the introduction of interferon (IFN)-alpha monotherapy in the early 1990s to the approval of telaprevir- and boceprevir-based triple therapies with pegylated (PEG)-IFN-alpha and ribavirin (RBV) in 2011, the chances of curing patients infected with HCV genotype 1 have improved dramatically to reach approximately 70%. Significant further improvements that may cure virtually all HCV patients with an all-oral, IFN-free regimen are becoming progressively available. Key Messages: Historically, a PEG-IFN/RBV combination therapy of patients with liver cirrhosis was associated with lower virological rates and a worse safety profile. The advent of the first protease inhibitor-based triple therapy was long expected, but the promise fell rapidly because of the numerous side effects and the requirement for intensive clinical management in cirrhotic patients. The newer direct-acting antivirals (DAAs) target the viral polymerase with either nucleos(t)ide analogues or nonnucleosidic inhibitors, the viral protease and the viral NS5A protein. Several clinical trials have now shown that a combination of sofosbuvir (nucleosidic polymerase inhibitor) with daclatasvir or ledipasvir (NS5A inhibitors), or sofosbuvir with simeprevir (protease inhibitor), or a combination of ABT-450 (protease inhibitor) with ritonavir (ABT 450/r), the nonnucleosidic polymerase inhibitor ABT-333 and the NS5A inhibitor ABT-267, can achieve a sustained virological response in up to 95% of naive patients or previously treated patients, even in those who failed prior treatment with first-generation protease inhibitors. The best treatment regimens enable the achievement of comparable results even in cirrhotics, while other regimens still require RBV or a longer treatment duration to achieve optimal results. This improved risk/benefit ratio justifies early access programs of IFN-free regimens for cirrhotic patients. The remaining difficult-to-treat patients are cirrhotics infected with HCV genotype 3 and those with decompensated cirrhosis, for whom novel DAA combinations should be evaluated in clinical trials. CONCLUSIONS: As new DAAs are becoming available in early access treatment programs, treatment strategy studies are being performed to optimize treatment regimens with respect to the choice of DAAs and treatment duration, based on viral genotypes, prior treatment response and the presence of liver cirrhosis. In the near future, this should allow: (i) a decrease in the complications of HCV-induced cirrhosis, (ii) liver transplantations to be performed in virally cured patients, and (iii) the rescue of patients in the worst clinical situation (decompensated cirrhosis and HCV recurrence on liver graft). PMID- 26159285 TI - The use of online discussions for post-clinical conference. AB - Nurse educators, at every level of pre-licensure nursing education, are charged with developing critical thinking skills within their students. Post-clinical conference is one teaching strategy that nurse educators can employ to help promote the development of critical thinking skills in pre-licensure nursing students. However, traditional face-to-face post-clinical conference is marred with issues and concerns, as identified in the nursing education literature. An alternative to face-to-face post-clinical conference, asynchronous online learning environment, mitigates the issues and concerns associated with traditional post-clinical conference. Adult learning theory supports the use of asynchronous online learning environment because the asynchronous online learning environment promotes student-centered teaching strategy in place of teacher centered learning, which by its nature traditional face-to-face post-clinical conference tends to support. PMID- 26159286 TI - Perinatal 17alpha-ethinylestradiol exposure affects formalin-induced responses in middle-aged male (but not female) rats. AB - 17alpha-Ethinylestradiol (EE), the main component of the contraceptive pill, is a synthetic estrogen found in rivers of the United States and Europe as an environmental contaminant. It is one of the most studied xenoestrogens due to its possible effect on the reproductive system. In the present study we evaluated the modulation of pain responses induced by formalin injection (licking, flexing, paw jerk) in 8-month-old male and female offspring of female rats treated with two different doses of EE (4ng/kg/day or 400ng/kg/day) during pregnancy and lactation. Spontaneous behaviors and gonadal hormone levels were also determined. Both concentrations of EE induced an increase of pain behaviors in males only, i.e. higher flexing and licking of the formalin-injected paw than in OIL-exposed rats, during the second, inflammatory, phase of the formalin test. Grooming duration was increased by EE exposure in both males and females. Prenatal EE exposure (both concentrations) decreased estradiol plasma levels in the formalin injected females but not in the males. These results underline the possibility that exposure to an environmental contaminant during the critical period of development can affect neural processes (such as those involved in pain modulation) during adulthood, indicating long-term changes in brain circuitry. However, such changes may be different in males and females. PMID- 26159287 TI - Peri-pubertal exposure to testicular hormones organizes response to novel environments and social behaviour in adult male rats. AB - Previous research has shown that exposure to testicular hormones during the peri pubertal period of life has long-term, organizational effects on adult sexual behaviour and underlying neural mechanisms in laboratory rodents. However, the organizational effects of peri-pubertal testicular hormones on other aspects of behaviour and brain function are less well understood. Here, we investigated the effects of manipulating peri-pubertal testicular hormone exposure on later behavioural responses to novel environments and on hormone receptors in various brain regions that are involved in response to novelty. Male rodents generally spend less time in the exposed areas of novel environments than females, and this sex difference emerges during the peri-pubertal period. Male Lister-hooded rats (Rattus norvegicus) were castrated either before puberty or after puberty, then tested in three novel environments (elevated plus-maze, light-dark box, open field) and in an object/social novelty task in adulthood. Androgen receptor (AR), oestrogen receptor (ER1) and corticotropin-releasing factor receptor (CRF-R2) mRNA expression were quantified in the hypothalamus, hippocampus and medial amygdala. The results showed that pre-pubertally castrated males spent more time in the exposed areas of the elevated-plus maze and light-dark box than post pubertally castrated males, and also confirmed that peri-pubertal hormone exposure influences later response to an opposite-sex conspecific. Hormone receptor gene expression levels did not differ between pre-pubertally and post pubertally castrated males in any of the brain regions examined. This study therefore demonstrates that testicular hormone exposure during the peri-pubertal period masculinizes later response to novel environments, although the neural mechanisms remain to be fully elucidated. PMID- 26159288 TI - Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential. AB - BACKGROUND: Low-risk patients suffering from prostate cancer (PCa) are currently placed under active surveillance rather than undergoing radical prostatectomy. However, clear parameters for selecting the right patient for each strategy are not available, and new biomarkers and treatment modalities are needed. Low molecular-weight protein tyrosine phosphatase (LMWPTP) could present such a target. OBJECTIVE: To correlate expression levels of LMWPTP in primary PCa to clinical outcome, and determine the role of LMWPTP in prostate tumor cell biology. DESIGN, SETTING, AND PARTICIPANTS: Acid phosphatase 1, soluble (ACP1) expression was analyzed on microarray data sets, which were subsequently used in Ingenuity Pathway Analysis. Immunohistochemistry was performed on a tissue microarray containing material of 481 PCa patients whose clinicopathologic data were recorded. PCa cell line models were used to investigate the role of LMWPTP in cell proliferation, migration, adhesion, and anoikis resistance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association between LMWPTP expression and clinical and pathologic outcomes was calculated using chi-square correlations and multivariable Cox regression analysis. Functional consequences of LMWPTP overexpression or downregulation were determined using migration and adhesion assays, confocal microscopy, Western blotting, and proliferation assays. RESULTS AND LIMITATIONS: LMWPTP expression was significantly increased in human PCa and correlated with earlier recurrence of disease (hazard ratio [HR]:1.99; p<0.001) and reduced patient survival (HR: 1.53; p=0.04). Unbiased Ingenuity analysis comparing cancer and normal prostate suggests migratory propensities in PCa. Indeed, overexpression of LMWPTP increases PCa cell migration, anoikis resistance, and reduces activation of focal adhesion kinase/paxillin, corresponding to decreased adherence. CONCLUSIONS: Overexpression of LMWPTP in PCa confers a malignant phenotype with worse clinical outcome. Prospective follow up should determine the clinical potential of LMWPTP overexpression. PATIENT SUMMARY: These findings implicate low-molecular-weight protein tyrosine phosphatase as a novel oncogene in prostate cancer and could offer the possibility of using this protein as biomarker or target for treatment of this disease. PMID- 26159289 TI - Simultaneous deletion of NOD1 and NOD2 inhibits in vitro alloresponses but does not prevent allograft rejection. AB - Pattern recognition receptors (PRRs) play an important role in host anti-donor responses to transplanted tissue. A key trigger of the host alloresponse involves recognition of foreign antigen presented on activated antigen presenting cells by the host T cells. Emerging data suggest that PRR blockade can abrogate host anti donor responses by interfering with activation of antigen presenting cells, particularly activation of dendritic cells. Our study asked whether blockade of a well-characterized family of intracellular PRRs, the NOD family, interfered with alloantigen recognition and allograft rejection. We found that deletion of either NOD1 or NOD2 in antigen presenting cells (APCs) had no effect on induction of T cell proliferation to alloantigen, but that simultaneous deletion of NOD1 and NOD2 significantly inhibited T cell responses. There was however no effect of the NOD deletion on skin graft rejection when NOD1*NOD2 skin was transplanted onto allogeneic hosts or when WT skin was transplanted onto NOD1*NOD2 deficient recipients. The conclusion of this study is that in vitro alloresponses are negatively impacted by the simultaneous deletion of NOD1 and NOD2, but that allograft rejection across a stringent allo barrier is not affected. Our results suggest that the NOD family members, NOD1 and NOD2, play a collaborative role in T cell activation by alloantigen and that their blockade in vitro can inhibit T cell responses. PMID- 26159290 TI - Laparoscopic repair of giant hiatal hernia. A single center experience. AB - INTRODUCTION: Giant hiatal hernia is a rare clinical entity with possibly serious complications, diagnosed mostly among older patients. The laparoscopic repair of such hernias is a therapeutic option, performed mostly in specialized centers by experienced surgeons. METHODS: From 1997 to 2012 fifty-five patients with giant hiatal hernia (median age of 72) were primarily treated by laparoscopic surgery at the surgical department of the Catholic Clinic Oberhausen. Demographic data, operating times, conversion rate, morbidity and mortality were recorded prospectively. Follow-up was conducted by means of a mailed questionnaire. RESULTS: Intraoperative complications occurred in 1,8% of the cases (n = 1). In this single case the procedure was converted to an open procedure due to technical difficulties imposed by hepatomegaly. The median operating time was 96 min (range, 30 to 350). Our rate of postoperative complications was 14,5% (n = 8). The median postoperative hospital stay was nine days. 14,5% (n = 8) of our patients underwent a redo-surgery for symptomatic recurrence. The median follow up was 64 months by means of a self-designed questionnaire. 34,5% (19/55) of the questioned patients responded to our survey. The difference between pre- and postoperative symptom intensity was found to be significant for heartburn (p < 0,001) and retrosternal/epigastric pain (p = 0,028). The difference was not found to be statistically significant for dysphagia (p = 0,8) and bloating (p = 0,3). 85% of the questioned patients stated they would have the operation again, if necessary. 80% reported an improvement of their overall quality of life. DISCUSSION: The laparoscopic repair of large hiatal hernias is a safe approach with an intraoperative complication rate of 1,8%, low post-operative morbidity (14,5%) and very low mortality (1,8%). There is a high patient satisfaction (85%) and a good postoperative quality of life (80%). CONCLUSION: The laparoscopic approach for repair of large hiatal hernias is a relatively safe method with significant long-term efficacy in terms of symptom control and quality of life. PMID- 26159292 TI - Physicochemical properties of 3D collagen-CS scaffolds for potential use in neural tissue engineering. AB - Collagen-based composite scaffolds have considerable potential due to their well known ability to regenerate skin, bone and cartilage. However, the precise composition and structure of scaffolds that optimize their interaction with neural cells remains incompletely understood and yet to be explored. In the present study, a new family of bi-component 3D scaffolds consisting of collagen (Col) and chondroitin sulphate (CS) were synthesized using a two-stage process: multiple freeze-drying followed by carbodiimide modification. Col-CS matrices had an average pore diameter of 31 MUm and a relatively high surface area to pore volume ratio. Importantly, the FTIR data indicated that the ratio between the intensity of amide III and 1452 cm(-1) for Col-CS scaffold was 0.87, which indicates that the Col triple helix was preserved during the formation of the bond between Col and CS. All experiments also clearly showed that the Col-CS matrices have a lower enzyme sensitivity and higher thermal resistance than Col alone. These differences are likely due to the relatively large amount of CS in the collagen sponges, which hinders access for attack at specific active sites of the Col triple helix. Improved binary composite scaffolds were designed for neural tissue engineering applications. PMID- 26159291 TI - Immunobiological barriers to xenotransplantation. AB - Binding of natural anti-pig antibodies in humans and nonhuman primates to carbohydrate antigens expressed on the transplanted pig organ, the most important of which is galactose-alpha1,3-galactose (Gal), activate the complement cascade, which results in destruction of the graft within minutes or hours, known as hyperacute rejection. Even if antibody is removed from the recipient's blood by plasmapheresis, recovery of antibody is associated with acute humoral xenograft rejection. If immunosuppressive therapy is inadequate, the development of high levels of T cell-dependent elicited anti-pig IgG similarly results in graft destruction, though classical acute cellular rejection is rarely seen. Vascular endothelial activation by low levels of anti-nonGal antibody, coupled with dysregulation of the coagulation-anticoagulation systems between pigs and primates, leads to a thrombotic microangiopathy in the graft that may be associated with a consumptive coagulopathy in the recipient. The most successful approach to overcoming these barriers is by genetically-engineering the pig to provide it with resistance to the human humoral and cellular immune responses and to correct the coagulation discrepancies between the two species. Organs and cells from pigs that (i) do not express the important Gal antigen, (ii) express a human complement-regulatory protein, and (iii) express a human coagulation regulatory protein, when combined with an effective immunosuppressive regimen, have been associated with prolonged pig graft survival in nonhuman primates. PMID- 26159293 TI - CiPA: Ongoing testing, future qualification procedures, and pending issues. AB - INTRODUCTION: The comprehensive in vitro proarrhythmia assay (CiPA) is a nonclinical, mechanism-based paradigm for assessing drug proarrhythmic liability. TOPICS COVERED: The first CiPA assay determines effects on cloned human cardiac ion channels. The second investigates whether the latter study-generated metrics engender proarrhythmic markers on a computationally reconstructed human ventricular action potential. The third evaluates conclusions from, and searches possibly missed effects by in silico analysis, in human stem cell-derived cardiomyocytes (hSC-CMs). CiPA ad hoc Expert-Working Groups have proposed patch clamp protocols for seven cardiac ion channels, a modified O'Hara-Rudy model for in silico analysis, detailed procedures for field (MEA) and action potential (VSD) measurements in hSC-CMs, and 29 reference drugs for CiPA assay testing and validation. DISCUSSION: CiPA adoption as drug development tool for identifying electrophysiological mechanisms conferring proarrhythmic liability to candidate drugs is a complex, multi-functional task requiring significant time, reflection, and efforts to be fully achieved. PMID- 26159295 TI - Bendable ITO-free Organic Solar Cells with Highly Conductive and Flexible PEDOT:PSS Electrodes on Plastic Substrates. AB - Flexible and transparent electrodes have great potential for photon transmission and charge-carrier collection for next generation electronics compared to rigid electronics with indium tin oxide (ITO)-coated glass substrates. This study describes a comprehensive study of the electrical, morphological, optical, structural, and mechanical properties of poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) films treated by methanol and methanesulfonic acid (MSA), which are coated on hydrophobic flexible plastic substrates. Such a film coated on hydrophobic plastic substrates exhibits a high conductivity up to 3560 S cm(-1) and a good mechanical flexibility. Moreover, the use of the films to fabricate bendable ITO-free organic solar cells (OSCs) integrated on plastic substrates was presented. The bendable devices based on P3HT:PCBM not only exhibit a high power conversion efficiency (PCE) up to 3.92%, which is comparable to 4.30% of the rigid devices with ITO-coated glass substrates, but also keep about 80% in PCE of the initial value after 100 time bending with a bending radius of 14 mm in the ambient atmosphere. This work provides a novel route to dramatically improve the conductivity of PEDOT: PSS electrodes, as well as the mechanical flexibility of highly efficient organic electronics with the flexible electrodes. PMID- 26159294 TI - Managing Medications During Home Hospice Cancer Care: The Needs of Family Caregivers. AB - CONTEXT: Family caregivers (FCGs) are often at the frontline of symptom management for patients with advanced illness in home hospice. FCGs' cognitive, social, and technical skills in complex medication management have been well studied in the literature; however, few studies have tested existing frameworks in clinical cases in home hospice. OBJECTIVES: This study sought to assess the applicability of caregiver medication management skills framework by Lau et al. in the context of family caregiving in home hospice to further the understanding of FCGs' essential medication management skills. METHODS: This was a secondary data analysis of 18 audio recorded home hospice visits transcribed verbatim; deductive content analysis of caregiver-nurse interactions was conducted. The target sample included FCGs of hospice patients who had cancer diagnoses in hospices located in the greater urban area of the Rocky Mountain West. Caregiver medication management skills were identified and categorized into the five domains of caregiver expertise. Exemplars of each domain were identified. RESULTS: An average of four medications (SD = 3.5) was discussed at each home hospice visit. Medication knowledge skills were observed in most home hospice visits (15 of 18). Teamwork skills were observed in 11 of 18 cases, followed by organizational and personhood skills (10 of 18). Symptom management skills occurred in 12 of 18 cases. An additional two subconstructs of the personhood domain-1) advocacy for the caregiver and 2) skills in discontinuing medications were proposed. CONCLUSION: These findings support framework by Lau et al. for caregiver medication management skills and expands on the existing domains proposed. Future interventions to assess FCGs' skills are recommended. PMID- 26159296 TI - PI3K/Akt in platelet integrin signaling and implications in thrombosis. AB - Blood platelets are anucleated circulating cells that play a critical role in hemostasis and are also implicated in arterial thrombosis, a major cause of death worldwide. The biological function of platelets strongly relies in their reactiveness to a variety of extracellular agonists that regulate their adhesion to extracellular matrix at the site of vascular injury and their ability to form rapidly growing cell aggregates. Among the membrane receptors expressed on the cell surface, integrins are crucial for both platelet activation, adhesion and aggregation. Integrin affinity for specific ligands is regulated by intracellular signaling pathways activated in stimulated platelets, and, once engaged, integrins themselves generate and propagate signals inside the cells to reinforce and consolidate platelet response and thrombus formation. Phosphatidylinositol 3 Kinases (PI3Ks) have emerged as crucial players in platelet activation, and they are directly implicated in the regulation of integrin function. This review will discuss the contribution of PI3Ks in platelet integrin signaling, focusing on the role of specific members of class I PI3Ks and their downstream effector Akt on both integrin inside-out and outside-in signaling. The contribution of the PI3K/Akt pathways stimulated by integrin engagement and platelet activation in thrombus formation and stabilization will also be discussed in order to highlight the possibility to target these enzymes in effective anti-thrombotic therapeutic strategies. PMID- 26159297 TI - Class I PI 3-kinases: Function and evolution. AB - In many human cell types, the class I phosphoinositide 3-kinases play key roles in the control of diverse cellular processes including growth, proliferation, survival and polarity. This is achieved through their activation by many cell surface receptors, leading to the synthesis of the phosphoinositide lipid signal, PIP3, which in turn influences the function of numerous direct PIP3-binding proteins. Here we review PI3K pathway biology and analyse the evolutionary distribution of its components and their functions. The broad phylogenetic distribution of class I PI3Ks in metazoa, amoebozoa and choannoflagellates, implies that these enzymes evolved in single celled organisms and were later co opted into metazoan intercellular communication. A similar distribution is evident for the AKT and Cytohesin groups of downstream PIP3-binding proteins, with other effectors and pathway components appearing to evolve later. The genomic and functional phylogeny of regulatory systems such as the PI3K pathway provides a framework to improve our understanding of the mechanisms by which key cellular processes are controlled in humans. PMID- 26159298 TI - Gonadal transcriptome analysis of wild contaminated female European eels during artificial gonad maturation. AB - Since the early 1980s, the population of European eels (Anguilla anguilla) has dramatically declined. Nowadays, the European eel is listed on the red list of threatened species (IUCN Red List) and is considered as critically endangered of extinction. Pollution is one of the putative causes for the collapse of this species. Among their possible effects, contaminants gradually accumulated in eels during their somatic growth phase (yellow eel stage) would be remobilized during their reproductive migration leading to potential toxic events in gonads. The aim of this study was to investigate the effects of organic and inorganic contaminants on the gonad development of wild female silver eels. Female silver eels from two sites with differing contamination levels were artificially matured. Transcriptomic analyses by means of a 1000 candidate gene cDNA microarray were performed on gonads after 11weeks of maturation to get insight into the mechanisms of toxicity of contaminants. The transcription levels of several genes, that were associated to the gonadosomatic index (GSI), were involved in mitotic cell division but also in gametogenesis. Genes associated to contaminants were mainly involved in the mechanisms of protection against oxidative stress, in DNA repair, in the purinergic signaling pathway and in steroidogenesis, suggesting an impairment of gonad development in eels from the polluted site. This was in agreement with the fact that eels from the reference site showed a higher gonad growth in comparison to contaminated fish. PMID- 26159299 TI - Transcriptional response of two metallothionein genes (OcMT1 and OcMT2) and histological changes in Oxya chinensis (Orthoptera: Acridoidea) exposed to three trace metals. AB - This study evaluated the transcriptional responses of two metallothionein (MT) genes (OcMT1 and OcMT2) in various tissues (brain, optic lobe, Malpighian tubules, fat bodies, foregut, gastric caeca, midgut and hindgut) of Oxya chinensis (Thunberg) (Orthoptera: Acridoidea) after exposed to the trace metals cadmium (Cd), copper (Cu) and zinc (Zn) for 48h. The study revealed that the exposure of O. chinensis to each of the three metals at the median lethal concentration (LC50) or lower concentration(s) up-regulated the transcriptions of both OcMT1 and OCMT2 in the eight tissues except for OcMT1 and OcMT2 with Cd in brain and gastric caeca, respectively, and OcMT2 with Cu in gastric caeca. These results suggested that the exposure of O. chinensis to the metals may enhance MT biosynthesis that protects tissues by binding these metals in various tissues. To examine possible histopathological effect of the metals, we examined the histological changes in the fat bodies after O. chinensis was exposed to each of these metals at LC50. The exposure of Cd significantly reduced the size and number of adipocytes as compared with the control. However, such an effect was not observed in O. chinensis exposed to either Cu or Zn. These results suggested that fat bodies might be either significantly affected by Cd or play a crucial role in detoxification of excessive trace metals. PMID- 26159300 TI - Mutation in galP improved fermentation of mixed sugars to succinate using engineered Escherichia coli AS1600a and AM1 mineral salts medium. AB - Escherichia coli KJ122 was engineered to produce succinate from glucose using the wild type GalP for glucose uptake instead of the native phosphotransferase system (ptsI mutation). This strain now ferments 10% xylose poorly. Mutants were selected by serial transfers in AM1 mineral salts medium with 10% xylose. Clones from this population all exhibited a similar improvement, co-fermentation of an equal mixture of xylose and glucose. One of these, AS1600a, produced 84.26 +/- 1.37 g/L succinate, equivalent to that produced by the parent (KJ122) from 10% glucose (85.46 +/- 1.78 g/L). AS1600a was sequenced and found to contain a mutation in galactose permease (GalP, G236D). This mutation was shown to be responsible for the improvement in fermentation using KJDeltagalP as the host and expression vectors with native galP and with mutant galP(*). Strain AS1600a and KJDeltagalP(pLOI5746; galP(*)) also co-fermented a mixture of glucose, xylose, arabinose, and galactose in sugarcane bagasse hydrolysate using mineral salts medium. PMID- 26159301 TI - Effects of water washing and torrefaction pretreatments on rice husk pyrolysis by microwave heating. AB - The influences of water washing, torrefaction and combined water washing torrefaction pretreatments on microwave pyrolysis of rice husk samples were investigated. The results indicated that the process of combined water washing torrefaction pretreatment could effectively remove a large portion of inorganics and improve the fuel characteristics to a certain extent. The gas products were rich in combustible compositions and the syngas quality was improved by pretreatment process. The liquid products contained less moisture content, acids and furans, while more concentrated phenols and sugars from microwave pyrolysis of rice husk after pretreatments, especially after the combined water washing torrefaction pretreatment. Biochar, produced in high yield, has the alkaline pH (pH 8.2-10.0) and high surface area (S(BET) 157.81-267.84 m(2)/g), they have the potential to be used as soil amendments. It is noteworthy that water washing increased the pore surface area of biochar, but torrefaction reduced the pore surface area. PMID- 26159302 TI - Impact of volatile fatty acids on microbial electrolysis cell performance. AB - This study investigated the performance of microbial electrolysis cells (MECs) fed with three common fermentation products: acetate, butyrate, and propionate. Each substrate was fed to the reactor for three consecutive-batch cycles. The results showed high current densities for acetate, but low current densities for butyrate and propionate (maximum values were 6.0 +/- 0.28, 2.5 +/- 0.06, 1.6 +/- 0.14 A/m(2), respectively). Acetate also showed a higher coulombic efficiency of 87 +/- 5.7% compared to 72 +/- 2.0 and 51 +/- 6.4% for butyrate and propionate, respectively. This paper also revealed that acetate could be easily oxidized by anode respiring bacteria in MEC, while butyrate and propionate could not be oxidized to the same degree. The utilization rate of the substrates in MEC followed the order: acetate > butyrate > propionate. The ratio of suspended biomass to attached biomass was approximately 1:4 for all the three substrates. PMID- 26159303 TI - Expression of Paxillin is Correlated with Clinical Prognosis in Colorectal Cancer Patients. AB - BACKGROUND: The aim of this study was to investigate the expression of Paxillin in colorectal carcinoma and its significance in clinical prognosis. MATERIAL AND METHODS: Tissue specimens from 242 colorectal cancer patients who underwent radical resection were collected in Shaanxi Provincial People's Hospital from 2010 to 2014. The mRNA levels of Paxillin in colorectal cancer tissue and tissue adjacent to carcinoma of 62 patients were measured by quantitative real-time PCR. Immunohistochemistry staining was used to detect the expression of Paxillin in 242 samples of paraffin-embedded tissues. RESULTS: The mRNA and protein level of Paxillin in colorectal cancer tissues were significantly higher than those in the tissue adjacent to carcinoma (P<0.001 and P=0.003, respectively). The expression of Paxillin was significantly correlated to tumor histological grade (P<0.001), tumor size (P=0.01), serum CA199 level (P<0.001), the clinical TNM stage (P<0.001), and distant metastasis (P<0.001). Survival analysis showed that the prognosis of the patients with high expression of Paxillin was poorer than those with low expression of Paxillin (P=0.03). Cox proportional hazards model with stepwise selection showed that age, Paxillin expression level, and the clinical TNM stage were independent prognostic factors influencing survival for patients (P=0.01, P=0.004 and P<0.001, respectively). CONCLUSIONS : Paxillin was expressed at significantly higher levels in colorectal cancer tissues and might serve as a potential prognostic indicator in patients with colorectal cancer. PMID- 26159304 TI - Extra-long interglacial in Northern Hemisphere during MISs 15-13 arising from limited extent of Arctic ice sheets in glacial MIS 14. AB - Knowledge of the behavior of Northern Hemisphere (NH) ice sheets over the past million years is crucial for understanding the role of orbitally driven insolation changes on glacial/interglacial cycles. Here, based on the demonstrable link between changes in Chinese loess grain-size and NH ice-sheet extent, we use loess grain-size records to confirm that northern ice-sheets were restricted during marine oxygen isotope stage (MIS) 14. Thus, an unusually long NH interglacial climate of over 100 kyr persisted during MISs 15-13, much longer than expected from marine oxygen isotope records. Taking a global view of the paleoclimate records, MIS 14 inception seems to be a response to changes in Antarctic ice-sheets rather than to NH cooling. Orbital configuration in the two Polar regions shows that the onset of MIS 14 was forced by austral insolation changes, rather than by boreal summer insolation, as Milankovitch theory proposes. Our analysis of MIS 14 raises the possibility that southern insolation forcing may have played an important role in the inception of several other glacials. We suggest that the extra-long NH interglacial climate during MISs 15 13 provided favorable conditions for the second major dispersal episode of African hominins into Eurasia. PMID- 26159305 TI - Socioeconomic burden of hand, foot and mouth disease in children in Shanghai, China. AB - In the near future, the inactivated enterovirus 71 (EV71) vaccine is expected to become available on the market in China. Since EV71 is a major cause of hand, foot and mouth disease (HFMD), the vaccine is expected to significantly reduce the number of cases, as well as the detrimental economic effect of the disease. However, for a national vaccination strategy to be developed, policy-makers need more information on the socioeconomic burden of EV71 HFMD infection. Based on the 2011 population data, we estimated the clinical and economic effect of EV71 HFMD infection in children aged 0-9 years in Shanghai, China. The annual cost related to HFMD is >US$7.66 million for a population of 1.42 million children aged 0-9 years with an average cost of US$208.2/case. The extrapolated cost for EV71 HFMD infection was US$3.53 million, comprising 46.1% of the overall cost associated with HFMD. Around 97% of all of the HFMD-related expenses were paid for by the families creating a considerable economic burden. Our findings could provide the necessary recommendations on the most effective national EV71 vaccine implementation, as well as a baseline data for assessing the cost-effectiveness of the vaccine in China. PMID- 26159307 TI - Genetic analyses of GII.17 norovirus strains in diarrheal disease outbreaks from December 2014 to March 2015 in Japan reveal a novel polymerase sequence and amino acid substitutions in the capsid region. AB - A novel GII.P17-GII.17 variant norovirus emerged as a major cause of norovirus outbreaks from December 2014 to March 2015 in Japan. Named Hu/GII/JP/2014/GII.P17 GII.17, this variant has a newly identified GII.P17 type RNA-dependent RNA polymerase, while the capsid sequence displays amino acid substitutions around histo-blood group antigen (HBGA) binding sites. Several variants caused by mutations in the capsid region have previously been observed in the GII.4 genotype. Monitoring the GII.17 variant's geographical spread and evolution is important. PMID- 26159306 TI - MitoTALEN: A General Approach to Reduce Mutant mtDNA Loads and Restore Oxidative Phosphorylation Function in Mitochondrial Diseases. AB - We have designed mitochondrially targeted transcription activator-like effector nucleases or mitoTALENs to cleave specific sequences in the mitochondrial DNA (mtDNA) with the goal of eliminating mtDNA carrying pathogenic point mutations. To test the generality of the approach, we designed mitoTALENs to target two relatively common pathogenic mtDNA point mutations associated with mitochondrial diseases: the m.8344A>G tRNA(Lys) gene mutation associated with myoclonic epilepsy with ragged red fibers (MERRF) and the m.13513G>A ND5 mutation associated with MELAS/Leigh syndrome. Transmitochondrial cybrid cells harbouring the respective heteroplasmic mtDNA mutations were transfected with the respective mitoTALEN and analyzed after different time periods. MitoTALENs efficiently reduced the levels of the targeted pathogenic mtDNAs in the respective cell lines. Functional assays showed that cells with heteroplasmic mutant mtDNA were able to recover respiratory capacity and oxidative phosphorylation enzymes activity after transfection with the mitoTALEN. To improve the design in the context of the low complexity of mtDNA, we designed shorter versions of the mitoTALEN specific for the MERRF m.8344A>G mutation. These shorter mitoTALENs also eliminated the mutant mtDNA. These reductions in size will improve our ability to package these large sequences into viral vectors, bringing the use of these genetic tools closer to clinical trials. PMID- 26159308 TI - Emergence of a novel GII.17 norovirus - End of the GII.4 era? AB - In the winter of 2014/15 a novel GII.P17-GII.17 norovirus strain (GII.17 Kawasaki 2014) emerged, as a major cause of gastroenteritis outbreaks in China and Japan. Since their emergence these novel GII.P17-GII.17 viruses have replaced the previously dominant GII.4 genotype Sydney 2012 variant in some areas in Asia but were only detected in a limited number of cases on other continents. This perspective provides an overview of the available information on GII.17 viruses in order to gain insight in the viral and host characteristics of this norovirus genotype. We further discuss the emergence of this novel GII.P17-GII.17 norovirus in context of current knowledge on the epidemiology of noroviruses. It remains to be seen if the currently dominant norovirus strain GII.4 Sydney 2012 will be replaced in other parts of the world. Nevertheless, the public health community and surveillance systems need to be prepared in case of a potential increase of norovirus activity in the next seasons caused by this novel GII.P17-GII.17 norovirus. PMID- 26159309 TI - Coincidental detection of the first outbreak of carbapenemase-producing Klebsiella pneumoniae colonisation in a primary care hospital, Finland, 2013. AB - In Finland, occurrence of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) has previously been sporadic and related to travel. We describe the first outbreak of colonisation with KPC-KP strain ST512; it affected nine patients in a 137-bed primary care hospital. The index case was detected by chance when a non-prescribed urine culture was taken from an asymptomatic patient with suprapubic urinary catheter in June 2013. Thereafter, all patients on the 38 bed ward were screened until two screening rounds were negative and extensive control measures were performed. Eight additional KPC-KP-carriers were found, and the highest prevalence of carriers on the ward was nine of 38. All other patients hospitalised on the outbreak ward between 1 May and 10 June and 101 former roommates of KPC-KP carriers since January had negative screening results. Two screening rounds on the hospital's other wards were negative. No link to travel abroad was detected. Compared with non-carriers, but without statistical significance, KPC-KP carriers were older (83 vs 76 years) and had more often received antimicrobial treatment within the three months before screening (9/9 vs 90/133). No clinical infections occurred during the six-month follow-up. Early detection, prompt control measures and repetitive screening were crucial in controlling the outbreak. PMID- 26159310 TI - Current prevalence of multidrug-resistant organisms in long-term care facilities in the Rhine-Main district, Germany, 2013. AB - Multidrug-resistant organisms (MDRO) and in particular multidrug-resistant Gram negative organisms (MRGN) are an increasing problem in hospital care. However, data on the current prevalence of MDRO in long-term care facilities (LTCFs) are rare. To assess carriage rates of MDRO in LTCF residents in the German Rhine-Main region, we performed a point prevalence survey in 2013. Swabs from nose, throat and perineum were analysed for meticillin-resistant Staphylococcus aureus (MRSA), perianal swabs were analysed for extended-spectrum beta-lactamase (ESBL) producing organisms, MRGN and vancomycin-resistant enterococci (VRE). In 26 LTCFs, 690 residents were enrolled for analysis of MRSA colonisation and 455 for analysis of rectal carriage of ESBL/MRGN and VRE. Prevalences for MRSA, ESBL/MRGN and VRE were 6.5%, 17.8%, and 0.4%, respectively. MRSA carriage was significantly associated with MRSA history, the presence of urinary catheters, percutaneous endoscopic gastrostomy tubes and previous antibiotic therapy, whereas ESBL/MRGN carriage was exclusively associated with urinary catheters. In conclusion, this study revealed no increase in MRSA prevalence in LTCFs since 2007. In contrast, the rate of ESBL/MRGN carriage in German LTCFs was remarkably high. In nearly all positive residents, MDRO carriage had not been known before, indicating a lack of screening efforts and/or a lack of information on hospital discharge. PMID- 26159311 TI - Phylogenetic analysis of highly pathogenic avian influenza A(H5N8) virus outbreak strains provides evidence for four separate introductions and one between-poultry farm transmission in the Netherlands, November 2014. AB - Phylogenetic analysis of highly pathogenic avian influenza A(H5N8) virus strains causing outbreaks in Dutch poultry farms in 2014 provides evidence for separate introduction of the virus in four outbreaks in farms located 16-112 km from each other and for between-farm transmission between the third and fourth outbreak in farms located 550 m from each other. In addition, the analysis showed that all European and two Japanese H5N8 virus strains are very closely related and seem to originate from a calculated common ancestor, which arose between July and September 2014. Our findings suggest that the Dutch outbreak virus strain 'Ter Aar' and the first German outbreak strain from 2014 shared a common ancestor. In addition, the data indicate that the Dutch outbreak viruses descended from an H5N8 virus that circulated around 2009 in Asia, possibly China, and subsequently spread to South Korea and Japan and finally also to Europe. Evolution of the virus seemed to follow a parallel track in Japan and Europe, which supports the hypothesis that H5N8 virus was exchanged between migratory wild waterfowl at their breeding grounds in Siberia and from there was carried by migrating waterfowl to Europe. PMID- 26159314 TI - Expression of concern for Euro Surveill. 2015;20(25). PMID- 26159315 TI - Author's correction for Euro Surveill. 2015;20(25). PMID- 26159316 TI - Muscle activation during three sets to failure at 80 vs. 30% 1RM resistance exercise. AB - PURPOSE: The purpose of this study was to investigate electromyographic amplitude (EMG AMP), EMG mean power frequency (MPF), exercise volume (VOL), total work and muscle activation (iEMG), and time under concentric load (TUCL) during, and muscle cross-sectional area (mCSA) before and after 3 sets to failure at 80 vs. 30 % 1RM resistance exercise. METHODS: Nine men (mean +/- SD, age 21.0 +/- 2.4 years, resistance training week(-1) 6.0 +/- 3.7 h) and 9 women (age 22.8 +/- 3.8 years, resistance training week(-1) 3.4 +/- 3.5 h) completed 1RM testing, followed by 2 experimental sessions during which they completed 3 sets to failure of leg extension exercise at 80 or 30 % 1RM. EMG signals were collected to quantify EMG AMP and MPF during the initial, middle, and last repetition of each set. Ultrasound was used to assess mCSA pre- and post-exercise, and VOL, total work, iEMG, and TUCL were calculated. RESULTS: EMG AMP remained greater at 80 % than 30 % 1RM across all reps and sets, despite increasing 74 and 147 % across reps at 80 and 30 % 1RM, respectively. EMG MPF decreased across reps at 80 and 30 % 1RM, but decreased more and was lower for the last reps at 30 than 80 % 1RM (71.6 vs. 78.1 % MVIC). mCSA increased more from pre- to post-exercise for 30 % (20.2-24.1 cm(2)) than 80 % 1RM (20.3-22.8 cm(2)). VOL, total work, iEMG and TUCL were greater for 30 % than 80 % 1RM. CONCLUSION: Muscle activation was greater at 80 % 1RM. However, differences in volume, metabolic byproduct accumulation, and muscle swelling may help explain the unexpected adaptations in hypertrophy vs. strength observed in previous studies. PMID- 26159317 TI - Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors. AB - BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases. OBJECTIVE :To identify a proxy for ACEI-induced ADRs in prescription databases. SETTING: The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the Netherlands and has included 14,926 subjects aged 45 years or older. METHODS: All ACEI starters from 2000 to 2011 were identified using prescription data within the Rotterdam Study. Participants were classified into 4 mutually exclusive groups: continuing, discontinuing, switching to angiotensin receptor blockers (ARBs), and switching to other antihypertensives. For categorization, the maximum time-interval between two prescription periods was set at 3 and 6 months. Subsequently, primary care physician files were searched and clinical events were classified as definite ADRs, probable ADRs, possible ADRs and definite non-ADRs. Finally the accuracy of different prescription patterns as indicators of ADRs was evaluated. Main outcome measure Positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of the prescription patterns of the 4 groups were calculated. RESULTS: Totally, 1132 ACEI starters were included. The PPV for a definite ADR was 56.1 % for switchers to ARB, while the PPVs for switchers to other antihypertensives, and discontinuation were 39.5 and 19.5 %, respectively. After including probable ADRs and possible ADRs, PPVs for switchers to ARB increased to 68.3 and 90.5 %. A 6-month interval gave slightly higher PPVs compared to a 3-month interval (maximum 6.1 % higher). The differences in NPVs between 3 and 6-months interval groups were approximately 1.0 %. CONCLUSIONS: Switching ACEIs to ARBs is the best marker for ACEI-induced ADRs in prescription databases. PMID- 26159318 TI - Differential contribution of aortic and carotid sinus baroreflexes to control of heart rate and renal sympathetic nerve activity. AB - We examined the roles of aortic and carotid sinus baroreceptors in control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in 17 decerebrate rats. The baroreflex curves between the changes in mean arterial blood pressure (MAP) and HR or RSNA in response to intravenous injection of phenylephrine (10-20 MUg/kg) or nitroprusside (10 MUg/kg) were identified before and following sequential denervation of all four baroafferent nerves. The slope of the MAP-HR curve in the pressor range was decreased (P < 0.05) to 31 +/- 7% of the control following denervation of bilateral aortic nerves, whereas it remained substantial (72 +/- 10%) following denervation of bilateral carotid sinus nerves. The slope for HR became negligible following complete denervation of all four baroafferent nerves. In contrast, the slope of the MAP-RSNA curve decreased as the sequential baroafferent denervation progressed, irrespective of the denervation order, and it remained well as long as any single baroafferent nerve was intact. The similar influences of sequential baroafferent denervation on the responses of HR and RSNA were observed in the depressor range. Thus, it is likely that aortic and carotid sinus baroreceptors play differential roles in control of HR but they contribute similarly to control of RSNA. PMID- 26159319 TI - Molecular identification and expression of the Foxl2 gene during gonadal sex differentiation in northern snakehead Channa argus. AB - Channa argus is one of the most commercially important fish species in China. Studies show that males of C. argus grow faster than females at the same age. In order to explore the sex differentiation mechanism of C. argus, we isolated the full length of the sex-related gene Foxl2 cDNA and analysed its expression patterns during gonadal sex differentiation. Alignment of known Foxl2 amino acid sequences from vertebrates confirmed the conservation of the Foxl2 open reading frame, especially the forkhead domain and C-terminal region. Quantitative RT-PCR revealed that Foxl2 is predominantly expressed in brain, pituitary, gill and ovary, with its highest level in ovary but low levels in testis and other tissues, reflecting a potential role for Foxl2 in the brain-pituitary-gonad axis in C. argus. Our ontogenetic stage data showed that C. argus Foxl2 expression was significantly upregulated from 1 to 11 days posthatching (dph) and that the initiation of expression preceded the first anatomical ovarian differentiation (27 dph), suggesting that Foxl2 might play a potential role in early gonadal sex differentiation in C. argus. In addition, the Foxl2 protein was primarily located in granulosa cells surrounding the oocytes of mature C. argus, implying that Foxl2 may have a basic function in granulosa cell differentiation and the maintenance of oocytes. PMID- 26159320 TI - Molecular cloning and expression analysis of the retinoid X receptor (RXR) gene in golden pompano Trachinotus ovatus fed Artemia nauplii with different enrichments. AB - The retinoid X receptors (RXRs) are involved in the skeletal development and other biological process such as blood vessel formation and metabolism. Partial sequences of RXRalpha and beta genes were obtained, and their expressions were quantified on golden pompano Trachinotus ovatus at 28 days post hatching (DPH) to explore the molecular response to nutritional manipulation in fish larvae. As live food, Artemia nauplii were separately enriched with Nannochloropsis and Algamac 3080 and non-enriched Artemia nauplii (control) for fish feeding. The expressions of RXRs were detected in the embryos and fish larvae at early stages, suggesting that the skeletal development in golden pompano initiated before yolk re-sorption completion. Fish fed non-enriched Artemia nauplii ended up with higher jaw malformation. The highest specific growth rate was obtained when fish were fed with the Artemia nauplii enriched with Algamac 3080, and the lowest growth rate was observed when fish were fed with unenriched Artemia nauplii. The highest survival was obtained when fish were fed with non-enriched or Nannochloropsis-enriched Artemia nauplii. This study indicates that the use of enriched formula for Artemia nauplii can significantly affect the expression levels of RXRs and jaw malformation of golden pompano larvae, but there is no clear correlation between RXRs expressions and malformation rates when fish are subjected to nutrient challenge. PMID- 26159322 TI - A single thalamic target for deep brain stimulation to treat hemi-body pain syndrome. AB - BACKGROUND: Patients experiencing hemi-body pain represent a difficult problem when using the thalamus as a DBS target given its anatomical topology. METHODS: A 50-year-old HIV positive male underwent a right unilateral thalamic DBS to treat his severe left hemi-body central post-stroke pain following years of unsuccessful medication therapy. RESULTS: The final active contact of the electrode corresponded to stimulation of the nucleus ventrocaudalis parvocellularis internis, which has provided prolonged pain relief. CONCLUSION: To our knowledge this was the first time this pattern of pain was treated by a single thalamic DBS electrode, suggesting stimulation in this region may be a feasible target for achieving relief from chronic severe hemi-body pain. PMID- 26159321 TI - Oxytocin evokes a pulsatile PGE2 release from ileum mucosa and is required for repair of intestinal epithelium after injury. AB - We measured the short-circuit current (Isc) in rat ileum mucosa to identify the effect of oxytocin (OT) on mucosal secretion in small intestine. We identified a COX-2-derived pulsatile PGE2 release triggered by OT in rat ileum mucosa. OT receptors (OTR) are expressed in intestine crypt epithelial cells. Notably, OT evoked a dynamic change of [Ca(2+)]i in ileum crypts, which was responsible for this pulsatile release of PGE2. OT ameliorated 5-FU-, radiation- or DSS- induced injury in vivo, including the improvement of weight loss, reduced villus height and impaired survival of crypt transit-amplifying cells as well as crypt. Moreover, these protective effects of OT against intestinal injury were eliminated by coadministration of a selective inhibitor of PGE2, AH6809. Our findings strongly suggest that OT, a novel and important regulator of intestine mucosa barrier, is required for repair of intestinal epithelium after injury. Considering that OT is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent chemo-radiotherapy induced intestine injury or to treat IBD. PMID- 26159323 TI - Neural sources of performance decline during continuous multitasking. AB - Multitasking performance costs have largely been characterized by experiments that involve two overlapping and punctuated perceptual stimuli, as well as punctuated responses to each task. Here, participants engaged in a continuous performance paradigm during fMRI recording to identify neural signatures associated with multitasking costs under more natural conditions. Our results demonstrated that only a single brain region, the superior parietal lobule (SPL), exhibited a significant relationship with multitasking performance, such that increased activation in the multitasking condition versus the singletasking condition was associated with higher task performance (i.e., least multitasking cost). Together, these results support previous research indicating that parietal regions underlie multitasking abilities and that performance costs are related to a bottleneck in control processes involving the SPL that serves to divide attention between two tasks. PMID- 26159324 TI - Anatomical substrates and neurocognitive predictors of daily numerical abilities in mild cognitive impairment. AB - Patients with mild cognitive impairment experience difficulties in mathematics that affect their functioning in the activities of everyday life. What are the associated anatomical brain changes and the cognitive correlates underlying such deficits? In the present study, 33 patients with Mild Cognitive Impairments (MCI) and 29 cognitively normal controls underwent volumetric MRI, and completed the standardized battery of Numerical Activities of Daily Living (NADL) along with a comprehensive clinical neuropsychological assessment. Group differences were examined on the numerical tasks and volumetric brain measures. The gray (GM) and white matter (WM) volume correlates were also evaluated. The results showed that relative to controls, the MCI group had impairments in number comprehension, transcoding, written operations, and in daily activities involving time estimation and money usage. In the volumetric measures, group differences emerged for the transcoding subtask in the left insula and left superior temporal gyrus. Among MCI patients, number comprehension and formal numerical performance were correlated with volumetric variability in the right middle occipital areas and right frontal gyrus. Money-usage scores showed significant correlations with left mesial frontal cortex, right superior frontal and right superior temporal cortex. Regression models revealed that neuropsychological measures of long-term memory, language, visuo-spatial abilities, and abstract reasoning were predictive of the patients' decline in daily activities. The present findings suggest that early neuropathology in distributed cortical regions of the brain including frontal, temporal and occipital areas leads to a breakdown of cognitive abilities in MCI that impacts on numerical daily functioning. The findings have implications for diagnosis, clinical and domestic care of patients with MCI. PMID- 26159326 TI - Nursing is a global concern. AB - I had the privilege last month of speaking at the International Council of Nurses (ICN) conference in Seoul, South Korea, where about 7,000 nurses from 119 different countries explored the importance of global co-operation in nursing. PMID- 26159325 TI - Bonobo habituation in a forest-savanna mosaic habitat: influence of ape species, habitat type, and sociocultural context. AB - Habituation is the term used to describe acceptance by wild animals of a human observer as a neutral element in their environment. Among primates, the process takes from a few days for Galago spp. to several years for African apes. There are also intraspecies differences reflecting differences in habitat, home range, and ape-human relationship history. Here, we present the first study of the process of bonobo habituation in a fragmented habitat, a forest-savanna mosaic in the community-based conservation area led by the Congolese nongovernmental organization Mbou-Mon-Tour, Democratic Republic of the Congo. In this area, local people use the forest almost every day for traditional activities but avoid bonobos because of a traditional taboo. Because very few flight reactions were observed during habituation, we focused on quantitative parameters to assess the development of ape tolerance and of the tracking efficiency of observer teams. During the 18-month study period (May 2012-October 2013), 4043 h (319 days) were spent in the forest and bonobos were observed for a total of 405 h (196 contacts on 134 days). The average contact duration was stable over time (124 min), but the minimal distance during a contact decreased with habituation effort. Moreover, bonobo location and tracking efficiency, daily ratio of contact time to habituation effort, and the number of observations at ground level were positively correlated with habituation effort. Our observations suggest that bonobos become habituated relatively rapidly. These results are discussed in relation to the habitat type, ape species, and the local sociocultural context of villagers. The habituation process involves changes in ape behavior toward observers and also more complex interactions concerning the ecosystem, including the building of an efficient local team. Before starting a habituation process, knowledge of the human sociocultural context is essential to assess the balance between risks and benefits. PMID- 26159327 TI - RCN congress calls on government to solve emergency care crisis. AB - RCN MEMBERS have called on the college's ruling council to put pressure on UK governments to address the crisis in emergency departments (EDs). PMID- 26159328 TI - Wearing skinny jeans can stop blood flow to your legs. AB - A WOMAN spent four days in hospital recovering from nerve compression syndrome due to prolonged squatting in 'skinny' jeans. PMID- 26159329 TI - Co-location will ease pressure on services, claims report. AB - PATIENTS WHO attend emergency departments (EDs) know that alternative healthcare services are available to them but cannot always access them, a report has concluded. PMID- 26159330 TI - Patient safety fears follow staffing guideline decision. AB - A DECISION to halt development of a guideline for safe nurse staffing in urgent and emergency care settings could have major implications for services this winter, experts have warned. PMID- 26159333 TI - 'Too many' in crisis receive poor care, warns watchdog. AB - PEOPLE FACING mental health crises often think they are being judged and disrespected by emergency care staff, according to evidence compiled by the Care Quality Commission (CQC). PMID- 26159334 TI - Board's eye view - Changing roles. AB - AS HEALTHCARE providers, we rely on the latest technology. It helps us to understand and treat complex health conditions, and to model clinical trials. PMID- 26159338 TI - Call for action. AB - AT RCN congress in Bournemouth last month, I presented a resolution calling on council to put pressure on the UK governments to address the crisis in the emergency care service. This was presented on behalf of the East Dorset branch. PMID- 26159344 TI - Workforce planning for urgent care services. AB - Due to major changes in how emergency care is delivered across different communities, one emergency department is no longer like another. Some have separate minor injury provision, some are general departments that cater for all types of patient, while others are designated major trauma centres. These differences in patient profile affect the required numbers and skill mix of nursing establishments so that the nursing workforce in each cannot be predicated on patient numbers alone. This article describes the development by the RCN Emergency Care Association of an evidence-based staffing tool and how it can be used in practice. PMID- 26159345 TI - Emergency departments: better safe than sorry? AB - Emergency departments (EDs) in the UK are under increasing pressure, partly because people use them inappropriately for non-urgent conditions. As part of NHS Wales Choose Well campaign, Betsi Cadwaladr University Health Board, based in Bangor, Gwynedd, commissioned research into public perceptions of EDs and alternative urgent care services. This article reports on the findings, one of which is that parents tend to choose EDs as the default option when their children are unwell. The article also asks how public trust in other NHS services can be built so that demand on EDs can be reduced. PMID- 26159346 TI - Boxer's fracture: management and outcomes. AB - Boxer's fractures are common hand injuries, but their management varies greatly. Two years ago, a boxer's fracture care pathway was developed for use in the Royal London Hospital emergency department to standardise management. This article describes a clinical service evaluation carried out to test the validity of the pathway. The evaluation examined the functional outcomes of patients with boxer's fractures with 50 degrees or less palmar angulation who were discharged with no follow up. Findings show that most returned to work immediately and had good functional outcomes, which suggests that the pathway is safe for uncomplicated fractures with 50 degrees or less palmar angulation. PMID- 26159347 TI - Death anxiety among emergency care workers. AB - Death anxiety, or 'thanatophobia', is a state in which people experience negative emotional reactions in recognition of their own mortality. Emergency and unscheduled healthcare workers, such as emergency nurses and paramedics, are constantly reminded of death and therefore of their own mortality, and this makes them susceptible to death anxiety. This article introduces the concept of death anxiety, and highlights the need for staff, employers and universities to recognise its signs and symptoms. It also suggests some interventions that could prevent the debilitating effects of death anxiety, to improve staff's mental health and the care they provide to patients. PMID- 26159348 TI - Keeping staff in step. AB - BRIAN MCENTEGGART, clinical practice facilitator (CPF) for emergency care at University College Hospital, London, recently plastered the broken foot of an Irish dancer in Michael Flatley's Lord of the Dance show in London's West End. PMID- 26159349 TI - [In Process Citation]. PMID- 26159350 TI - Analysis of cell growth dynamics of Pediococcus acidilactici in the presence of inulin in an optimized microenvironment. AB - The present investigation deals with the optimization of cell growth rate of the candidate probiotic Pediococcus acidilactici in the presence of the specific prebiotic inulin. Three independent variables viz. concentration of inulin, concentration of glucose and pH have been selected for optimization study using response surface methodology. Theoretical analysis indicates that the maximum cell growth rate occurs at pH 7, 20 g/dm(3) concentration of inulin and 20 g/dm(3) concentration of glucose. Validation of these values has been done through a set of programmed experiments. Studies on cell dynamics in the presence of different concentrations of inulin have also been carried out to identify any limitation on the initial inulin concentration. Results clearly indicate that cell growth is enhanced with the increase in inulin concentration. However, there is a critical value of the prebiotic concentration (20 g/dm(3) inulin) beyond which the cell growth is inhibited. A summative type growth model has been proposed to explain the growth behaviour of P. acidilactici in the presence of the dual substrate, i.e. glucose and inulin. While growth on glucose follows Monod model, Haldane-type substrate-inhibited growth model holds good for growth on inulin. Intrinsic kinetic parameters for all the model equations have been determined experimentally. PMID- 26159351 TI - Development and validation of a stability indicating method for S-carboxymethyl-L cysteine and related degradation products in oral syrup formulation. AB - A stability-indicating method for the determination of S-carboxymethyl-L-cysteine and related degradation impurities in Exputex(r) 250mg/5mL syrup was developed in anion-exchange liquid chromatography mode. A forced degradation study supported the method development to ensure stability indicating conditions. Aqueous solutions of the active pharmaceutical ingredient and syrup samples at different pH-values were stress-tested in different thermal, light exposure and headspace conditions. One degradation product was detected in thermal stress studies at 60 degrees C and 80 degrees C in the pH range 5.0-7.0 and was identified by mass spectrometry as 5-oxo-thiomorpholine-3-carboxylic acid (lactam of carbocysteine). A second degradation product was only generated in moderately strong oxidizing conditions (0.5% H2O2 aqueous solution) and was identified as S-carboxymethyl-L cysteine-(R/S)-sulphoxide (carbocysteine sulphoxide). The method was developed on a Zorbax SAX column, in isocratic mode. The mobile phase consisted of 200mM phosphate solution at pH 4.0 and acetonitrile (50:50 v/v) and UV detection was performed at a wavelength of 205nm. The method was linear for carbocysteine (R>0.9982) over a concentration range of 2.5-50MUg/mL and 0.4-0.6mg/mL. Linearity for the impurities was shown from the LOQ to 50MUg/mL. Specificity was verified and accuracy demonstrated for the active ingredient and its degradation products in syrup samples at 3 levels around their respective specification limits. Repeatability, intermediate precision and inter-laboratory reproducibility were assessed on three commercial batches, analyzed in triplicate by two operators at both the transferring and the receiving site and demonstrated a successful method transfer to the manufacturing quality control laboratory. PMID- 26159353 TI - Chronic Myeloid Leukemia Monitoring after Imatinib Failure: Still More Questions than Answers. PMID- 26159352 TI - A Nanotechnology-Based Platform for Extending the Pharmacokinetic and Binding Properties of Anti-methamphetamine Antibody Fragments. AB - To address the need for effective medications to aid in the treatment of methamphetamine (METH) abuse, we used a nanotechnology approach to customize the in vivo behavior of an anti-METH single chain antibody (scFv7F9Cys). Anti-METH scFv7F9Cys was conjugated to dendrimer nanoparticles via a polyethylene glycol (PEG) linker to generate high-order conjugates termed dendribodies. We found that the high affinity (KD = 6.2 nM) and specificity for METH was unchanged after nanoparticle conjugation. The dendribodies were administered in an i.v. bolus to male Sprague Dawley rats after starting a s.c. infusion of METH. The PCKN values for clearance and volume of distribution of scFv7F9Cys after conjugation to dendrimers decreased 45 and 1.6-fold respectively, and the terminal elimination half-life increased 20-fold. Organ distribution of scFv7F9Cys and dendribody in blood and urine agreed well with the PCKN data. Renal clearance appeared to be the major route of elimination for both experimental medications. We have thus successfully developed a novel multivalent METH-binding nanomedicine by conjugating multiple anti-METH scFvs to dendrimer nanoparticles, extending the scFv half-life from 1.3 (+/- 0.3) to 26 (+/- 2.6) hr. These data suggest that the dendribody design could be a feasible platform for generating multivalent antibodies with customizable PCKN profiles. PMID- 26159354 TI - The Infectious and Noninfectious Dermatological Consequences of Flooding: A Field Manual for the Responding Provider. AB - Meteorological data show that disastrous floods are increasingly frequent and more severe in recent years, perhaps due to climatic changes such as global warming. During and after a flood disaster, traumatic injuries, communicable diseases, chemical exposures, malnutrition, decreased access to care, and even mental health disorders dramatically increase, and many of these have dermatological manifestations. Numerous case reports document typical and atypical cutaneous infections, percutaneous trauma, immersion injuries, noninfectious contact exposures, exposure to wildlife, and exacerbation of underlying skin diseases after such disasters as the 2004 Asian tsunami, Hurricane Katrina in 2005, and the 2010 Pakistan floods. This review attempts to provide a basic field manual of sorts to providers who are engaged in care after a flooding event, with particular focus on the infectious consequences. Bacterial pathogens such as Staphylococcus and Streptococcus are still common causes of skin infections after floods, with atypical bacteria also greatly increased. Vibrio vulnificus is classically associated with exposure to saltwater or brackish water. It may present as necrotizing fasciitis with hemorrhagic bullae, and treatment consists of doxycycline or a quinolone, plus a third-generation cephalosporin and surgical debridement. Atypical mycobacterial infections typically produce indolent cutaneous infections, possibly showing sporotrichoid spread. A unique nontuberculous infection called spam has recently been identified in Satowan Pacific Islanders; combination antibiotic therapy is recommended. Aeromonas infection is typically associated with freshwater exposure and, like Vibrio infections, immunocompromised or cirrhotic patients are at highest risk for severe disease, such as necrotizing fasciitis and sepsis. Various antibiotics can be used to treat Aeromonas infections. Melioidosis is seen mainly in Southeast Asia and Australia, particularly in rice farmers, and can remain latent for many years before presenting as the host's immunocompetence wanes. It can present with a variety of skin findings or as a nonspecific febrile illness, and preferred treatment consists of ceftazidime or a carbapenem with trimethoprim/sulfamethoxazole (TMP/SMX) for 2 weeks, then continuing TMP/SMX for at least 3 months. Leptospirosis is a waterborne zoonosis that is often prevalent after heavy rains or flooding. Different forms exist, including Fort Bragg fever, which produces a distinctive erythematous papular rash on the shins. Doxycycline is often sufficient; however, volume and potassium repletion may be necessary if renal involvement exists. Chromobacterium violaceum infection may occur after open skin is exposed to stagnant or muddy water. Cultured colonies produce a unique violacein pigment, and treatment typically consists of a carbapenem. Both typical and atypical fungal infections are increased in the flooding disaster scenario, such as dermatophytosis, chromoblastomycosis, blastomycosis, and mucormycosis. Appropriate antifungals should be used. In addition, land inundated with water expands the habitat for parasites and/or vectors, thus increased vigilance for regional parasitic infections is necessary after a flood. Lastly, noninfectious consequences of a flooding disaster are also common and include miliaria, immersion foot syndromes, irritant and allergic contact dermatitis, traumatic wounds and animal bites, and arthropod assault, as well as exacerbation of existing skin conditions such as atopic dermatitis, psoriasis, and alopecia areata due to increased stress or nonavailability of daily medications. PMID- 26159355 TI - Percutaneous Renal Tumor Ablation: Radiation Exposure During Cryoablation and Radiofrequency Ablation. AB - INTRODUCTION: Once reserved solely for non-surgical cases, percutaneous ablation is becoming an increasingly popular treatment option for a wider array of patients with small renal masses and the radiation risk needs to be better defined as this transition continues. MATERIALS AND METHODS: Retrospective review of our renal tumor ablation database revealed 425 patients who underwent percutaneous ablation for treatment of 455 renal tumors over a 5-year time period. Imparted radiation dose information was reviewed for each procedure and converted to effective patient dose and skin dose using established techniques. Statistical analysis was performed with each ablative technique. RESULTS: For the 331 cryoablation procedures, the mean DLP was 6987 mGycm (SD = 2861) resulting in a mean effective dose of 104.7 mSv (SD = 43.5) and the mean CTDIvol was 558 mGy (SD = 439) resulting in a mean skin dose of 563.2 mGy (SD = 344.1). For the 124 RFA procedures, the mean DLP was 3485 mGycm (SD = 1630) resulting in a mean effective dose of 50.3 mSv (SD = 24.0) and the mean CTDIvol was 232 mGy (SD = 149) resulting in a mean skin dose of 233.2 mGy (SD = 117.4). The difference in patient radiation exposure between the two renal ablation techniques was statistically significant (p < 0.001). CONCLUSION: Both cryoablation and RFA imparted an average skin dose that was well below the 2 Gy deterministic threshold for appreciable sequela. Renal tumor cryoablation resulted in a mean skin and effective radiation dose more than twice that for RFA. The radiation exposure for both renal tumor ablation techniques was at the high end of the medical imaging radiation dose spectrum. PMID- 26159356 TI - Transcatheter Embolisation of Proximal Type 1 Endoleaks Following Endovascular Aneurysm Sealing (EVAS) Using the Nellix Device: Technique and Outcomes. AB - AIM: To evaluate the technical success and mid-term outcomes following transcatheter embolisation of type 1a endoleak after Nellix endovascular aneurysm sealing (EVAS). MATERIALS AND METHODS: Seven patients (5 men; mean age 83; range 79-90) underwent transcatheter embolisation between July 2013 and August 2014. The average time from EVAS to embolisation was 136 days (range 6-301) and from endoleak diagnosis to embolisation was 20 days (range 2-50). Embolisation was performed with coils and Onyx in six cases and Onyx only in one case. Technical success, imaging and clinical outcomes of embolisation were reviewed. Technical success was defined as elimination of the endoleak on completion angiography and first imaging follow-up. Clinical success was defined as unchanged or decreased aneurysm sac size on subsequent follow-up (average 8 months; range 103-471 days). RESULTS: All cases were technically successful. One patient required a second endovascular procedure following Onyx reflux into the Nellix endograft and another patient required surgical closure of a brachial puncture site. All patients are endoleak free with stable sac size on the latest available follow-up imaging. CONCLUSION: If a type 1 endoleak occurs after EVAS, embolisation using Onyx with or without coils is feasible and effective with high technical success and freedom from endoleak recurrence at mid-term follow-up. PMID- 26159358 TI - Studies on the interaction of the food colorant tartrazine with double stranded deoxyribonucleic acid. AB - Interaction of the food additive tartrazine with double-stranded DNA was studied by spectroscopic and calorimetric techniques. Absorbance studies revealed that tartrazine exhibited hypochromism in the presence of DNA without any bathochromic effects. Minor groove displacement assay of DAPI and Hoechst 33258 suggested that tartrazine binds in the minor groove of DNA. The complexation was predominantly entropy driven with a smaller but favorable enthalpic contribution to the standard molar Gibbs energy. The equilibrium constant was evaluated to be (3.68 +/- .08) * 10(4) M(-1) at 298.15 K. The negative standard molar heat capacity value along with an enthalpy-entropy compensation phenomenon proposed the involvement of dominant hydrophobic forces in the binding process. Tartrazine enhanced the thermal stability of DNA by 7.53 K under saturation conditions. PMID- 26159357 TI - Radiotherapy dose escalation with concurrent chemotherapy in locally advanced cervix cancer is feasible. AB - BACKGROUND: To test the feasibility of radiotherapy dose escalation using volumetric arc therapy (VMAT) and image-guided radiotherapy (IGRT) with concurrent chemotherapy in locally advanced cervix cancer (LACC) and compare this with whole-pelvis three-dimensional conformal radiation therapy (CRT) in terms of clinical toxicity. METHODS: Database was reviewed for all LACC patients treated during 2011 and 2012. Twenty patients who were treated with escalated dose of radiotherapy using VMAT were selected for analysis. A matched cohort of 40 patients who had 3DCRT between 2005 and 2008 was selected as control. Mean basal hemoglobin, average weekly hemoglobin, and maximal drop in hemoglobin were measured for both 3DCRT and VMAT groups and treatment toxicity scored according to RTOG criteria. Charts were also reviewed for other acute and late toxicities including the rate of compliance with prescribed treatment. RESULTS: Mean age was 46 (30-63) and 47 years (33-67), mean tumor size was 5.5 and 5 cm and blood transfusion rate was 55 and 45 % in CRT and VMAT groups, respectively. Hemoglobin toxicity (Grade I-II) was encountered in 97.5 and 90 % (p 0.0.3) while Grade I III Leukopenia was 90 and 70 % (p 0.02), respectively. There was no Grade 3 or 4 GI or GU toxicity. CONCLUSION: VMAT/IGRT with dose escalation is feasible in LACC without excessive toxicity as compared to CRT "Box". We propose a randomized control trial of this novel approach of higher radiation dose and volume against the standard prescription based on CRT. PMID- 26159359 TI - Biochemical, Histopathological and Immunohistochemical Evaluation of the Protective and Therapeutic Effects of Thymoquinone against Ischemia and Ischemia/Reperfusion Injury in the Rat Ovary. AB - AIM: To evaluate the antioxidant effects of thymoquinone (TQ) and to investigate the biochemical, histopathological and immunohistochemical changes in experimental rat ovarian torsion. METHODS: A total of 48 female adult rats were used in this study and randomly divided into 7 groups: (1) sham operation; (2) bilateral 3-hour ovarian ischemia; (3) 3-hour ischemia and 3-hour reperfusion; (4) and (5) rats were administered 20 and 40 mg/kg of TQ, respectively, before 0.5 h of ischemia, and then 3 h of ovarian ischemia was applied; (6) and (7) 3 hour ovarian ischemia was applied; 2.5 h after the induction of ischemia, rats were administered the same doses of TQ; at the end of 3 h of ischemia, a 3-hour reperfusion was applied. Histologic changes under light microscopy, immunoreactivity for anticaspase-3 and serum levels of malondialdehyde, interleukin-6, catalase and glutathione peroxidase were noted and compared between the 7 groups. RESULTS: Ischemia and ischemia/reperfusion cause a deterioration of biochemical and histopathological parameters. Administration of TQ seems to reverse these alterations and alleviate the injury. Antioxidant defense mechanisms appear to be enhanced by the administration of TQ. CONCLUSION: TQ at different doses attenuates ovarian ischemia and ischemia/reperfusion injury in rats. PMID- 26159360 TI - Suppression of Serum Prolactin Levels after Sports Concussion with Prompt Resolution Upon Independent Clinical Assessment To Permit Return-to-Play. AB - A significant outflow of neurotransmitters and metabolites with associated enhanced cortical excitation occurs after concussive head trauma. Cellular changes in the acute post-injury period cannot be observed directly in humans, and as such, require indirect evidence from systems sufficiently sensitive to central neuronal cellular excitation. Dopamine is a neurotransmitter with numerous targets in the central and peripheral nervous system. Changes to central dopaminergic tone result in reciprocal responses to the level of serum prolactin (PRL). Thus, a concussion may lead to abnormal dopaminergic tone, resulting in dynamic perturbations in the serum PRL concentration. To determine the effect of concussion on serum PRL concentrations, venipuncture was performed in the morning in four male intercollegiate athletes (age, 20 +/- 1 years; height, 71 +/- 5 inches; weight, 174 +/- 21 pounds) within 48 h of concussion and again at 7 and 14 days post-injury. Serum PRL concentrations for each visit were categorized by quartile within the normal range. In all athletes, serum PRL concentrations increased from the lower quartiles in samples obtained closer to the time of injury to the higher quartiles at 14 days post-injury. These serum PRL changes accompanied the resolution of symptoms and the clinical decision to permit return to-play. It may be postulated that transient augmentation of central dopaminergic tone resulted in inhibition of PRL secretion early after concussion and that disinhibition of PRL release occurred when central dopaminergic tone subsequently returned to baseline levels. This novel observation provides evidence for dopaminergic dysfunction after concussion that may be tracked by determination of serum PRL levels. PMID- 26159361 TI - ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP/AIF Pathway. AB - BACKGROUND/AIMS: Stroke is among the top causes of death worldwide. Neuroprotective agents are thus considered as potentially powerful treatment of stroke. METHODS: Using both HT22 cells and male Sprague-Dawley rats as in vitro and in vivo models, we investigated the effect of NaHS, an exogenous donor of H2S, on the focal cerebral ischemia-reperfusion (I/R) induced brain injury. RESULTS: Administration of NaHS significantly decreased the brain infarcted area as compared to the I/R group in a dose-dependent manner. Mechanistic studies demonstrated that NaHS-treated rats displayed significant reduction of malondialdehyde content, and strikingly increased activity of superoxide dismutases and glutathione peroxidase in the brain tissues compared with I/R group. The enhanced antioxidant capacity as well as restored mitochondrial function are NaHS-treatment correlated with decreased cellular reactive oxygen species level and compromised apoptosis in vitro or in vivo in the presence of NaHS compared with control. Further analysis revealed that the inhibition of PARP 1 cleavage and AIF translocation are involved in the neuroprotective effects of NaHS. CONCLUSION: Collectively, our results suggest that NaHS has potent protective effects against the brain injury induced by I/R. NaHS is possibly effective through inhibition of oxidative stress and apoptosis. PMID- 26159362 TI - Paramagnetic molecule induced strong antiferromagnetic exchange coupling on a magnetic tunnel junction based molecular spintronics device. AB - This paper reports our Monte Carlo (MC) studies aiming to explain the experimentally observed paramagnetic molecule induced antiferromagnetic coupling between ferromagnetic (FM) electrodes. Recently developed magnetic tunnel junction based molecular spintronics devices (MTJMSDs) were prepared by chemically bonding the paramagnetic molecules between the FM electrodes along the tunnel junction's perimeter. These MTJMSDs exhibited molecule-induced strong antiferromagnetic coupling. We simulated the 3D atomic model analogous to the MTJMSD and studied the effect of molecule's magnetic couplings with the two FM electrodes. Simulations show that when a molecule established ferromagnetic coupling with one electrode and antiferromagnetic coupling with the other electrode, then theoretical results effectively explained the experimental findings. Our studies suggest that in order to align MTJMSDs' electrodes antiparallel to each other, the exchange coupling strength between a molecule and FM electrodes should be ~50% of the interatomic exchange coupling for the FM electrodes. PMID- 26159363 TI - Body Mass Index, Outcomes, and Mortality Following Cardiac Surgery in Ontario, Canada. AB - BACKGROUND: The "obesity paradox" reflects an observed relationship between obesity and decreased morbidity and mortality, suggesting improved health outcomes for obese individuals. Studies examining the relationship between high body mass index (BMI) and adverse outcomes after cardiac surgery have reported conflicting results. METHODS AND RESULTS: The study population (N=78 762) was comprised of adult patients who had undergone first-time coronary artery bypass (CABG) or combined CABG/aortic valve replacement (AVR) surgery from April 1, 1998 to October 31, 2011 in Ontario (data from the Institute for Clinical Evaluative Sciences). Perioperative outcomes and 5-year mortality among pre-defined BMI (kg/m(2)) categories (underweight <20, normal weight 20 to 24.9, overweight 25 to 29.9, obese 30 to 34.9, morbidly obese >34.9) were compared using Bivariate analyses and Cox multivariate regression analysis to investigate multiple confounders on the relationship between BMI and adverse outcomes. A reverse J shaped curve was found between BMI and mortality with their respective hazard ratios. Independent of confounding variables, 30-day, 1-year, and 5-year survival rates were highest for the obese group of patients (99.1% [95% Confidence Interval {CI}, 98.9 to 99.2], 97.6% [95% CI, 97.3 to 97.8], and 90.0% [95% CI, 89.5 to 90.5], respectively), and perioperative complications lowest. Underweight and morbidly obese patients had higher mortality and incidence of adverse outcomes. CONCLUSIONS: Overweight and obese patients had lower mortality and adverse perioperative outcomes after cardiac surgery compared with normal weight, underweight, and morbidly obese patients. The "obesity paradox" was confirmed for overweight and moderately obese patients. This may impact health resource planning, shifting the focus to morbidly obese and underweight patients prior to, during, and after cardiac surgery. PMID- 26159364 TI - [Low-grade systemic inflammation and the development of metabolic diseases: from the molecular evidence to the clinical practice]. AB - BACKGROUND: Systemic inflammation is characterised by high circulating levels of inflammatory cytokines and increased macrophage infiltration in peripheral tissues. Most importantly, this inflammatory state does not involve damage or loss of function of the infiltrated tissue, which is a distinctive feature of the low-grade systemic inflammation. The term "meta-inflammation" has also been used to refer to the low-grade systemic inflammation due to its strong relationship with the development of cardio-metabolic diseases in obesity. OBJECTIVE: A review is presented on the recent clinical and experimental evidence concerning the role of adipose tissue inflammation as a key mediator of low-grade systemic inflammation. Furthermore, the main molecular mechanisms involved in the inflammatory polarization of macrophages with the ability to infiltrate both the adipose tissue and the vascular endothelium via activation of toll-like receptors by metabolic damage-associated molecular patterns, such as advanced glycation-end products and oxidized lipoproteins, is discussed. Finally, a review is made of the pathogenic mechanisms through which the low-grade systemic inflammation contributes to develop insulin resistance, dyslipidaemia, atherogenesis, type 2 diabetes, and hypertension in obese individuals. CONCLUSIONS: A better understanding of the molecular mechanisms of low-grade systemic inflammation in promoting cardio-metabolic diseases is necessary, in order to further design novel anti-inflammatory therapies that take into consideration clinical data, as well as the circulating levels of cytokines, immune cells, and metabolic damage associated molecular patterns in each patient. PMID- 26159365 TI - [Video-assisted thoracic surgery diagnosis of mucinous (colloid) lung adenocarcinoma: Case report]. AB - BACKGROUND: Mucinous colloid lung adenocarcinoma is an uncommon variant of lung carcinomas with similar features to tumours seen in the gastrointestinal tract. To distinguish between these tumours and other mucinous lung tumours, such as mucinous bronchioloalveolar cell carcinomas and metastatic mucinous lesions could be difficult with small biopsy specimens from fine needle aspiration. CLINICAL CASE: The case is described of a 49-year-old female with history of dyspnoea and cough with bloody sputum and weight lose. Thorax axial computed tomography demonstrated a right lower lobe spiculated mass with calcifications. Transthoracic computed tomography- guided fine needle biopsy reported negative results, and the biopsy obtained with video-assisted thoracic surgery was useful for an adequate cytology report of a colloid variant of mucinous lung adenocarcinoma. CONCLUSION: Video-assisted thoracic surgery is an appropriate option for obtaining a larger specimen in those cases where small biopsies are inconclusive for the diagnosis of thoracic pathologies such as malignant tumours. PMID- 26159366 TI - [Abdominal compartment syndrome by tension pneumoperitoneum secondary to barotrauma. Presentation case]. AB - BACKGROUND: Pneumoperitoneum is defined as the existence of extraluminal air in the abdominal cavity. In 80-90% of cases is due to perforation of a hollow organ. However, in 10-15% of cases, it is nonsurgical pneumoperitoneum. OBJECTIVE: The case of a patient undergoing mechanical ventilation, developing abdominal compartment syndrome tension pneumoperitoneum is reported. CLINICAL CASE: Female, 75 years old asking for advise due to flu of long term duration. Given her respiratory instability, admission to the Intensive Care Unit is decided. It is then intubated and mechanically ventilated. Chest x-ray revealed a large pneumoperitoneum but no pneumothorax neither mediastinum; and due to the suspicion of viscera perforation with clinical instability secondary to intra abdominal hypertension box, emergency surgery was decided. CONCLUSIONS: When discarded medical history as a cause of pneumoperitoneum, it is considered that ventilation is the most common cause. Benign idiopathic or nonsurgical pneumoperitoneum, can be be treated conservatively if the patient agrees. But if intraabdominal hypertension prevails, it can result in severe respiratory and hemodynamic deterioration, sometimes requiring abdominal decompression to immediately get lower abdominal pressure and thus improve hemodynamic function. PMID- 26159367 TI - [Histopathological evaluation of the subtotal laryngectomy specimen]. AB - INTRODUCTION: The goal of conservative surgical treatment of laryngeal cancer is to obtain oncological control with preservation of laryngeal function. The concept of laryngeal function preservation should be understood as the preservation of the patient's ability to breathe normally with neither tracheostomy nor aspiration, and maintaining intelligible speech. This can be achieved by a balance between two fundamental aspects, proper patient selection (based on tumour extension and preoperative laryngeal function), and an adequate histopathological analysis of the surgical specimen. Supracricoid subtotal laryngectomy is the voice conservative surgical technique that offers the best possibility of control in patients with locally advanced laryngeal cancer. The proper histopathological analysis allows staging and selecting patients for adjuvant therapy, avoiding unnecessary ones as well as designing monitoring and surveillance programs based on risk factors. OBJECTIVE: To highlight key points in the histopathological evaluation of the surgical specimen of a subtotal laryngectomy. CONCLUSION: The proper communication between the surgeon and pathologist, offering complete information on preoperative clinical evaluation and the knowledge of the key points in the evaluation of the surgical specimen (sites of tumour leakage and surgical resection margins) are fundamental parameters to achieve a proper histopathological evaluation of the surgical specimen. PMID- 26159368 TI - [Cervical sympathetic chain schwannoma associated with parathyroid adenoma]. AB - BACKGROUND: Schwannoma is a rare benign tumor derived from nerve sheaths. When derived from the cervical sympathetic chain, it usually presents itself as an asymptomatic mass located in the posterior cervical region, at paravertebral level. Its diagnosis is not easy, usually requiring multiple imaging tests. Its differential diagnosis includes parathyroid adenoma. CLINICAL CASE: A new case of schwannoma of the cervical sympathetic chain in a patient with a synchronous overactive parathyroid adenoma is reported. This case adds to the sixty described in the literature, although to our knowledge no association between schwannoma and parathyroid adenoma has been reported to date. CONCLUSIONS: Despite being a benign tumor, its treatment is a complete surgical resection. The most common complication after the surgery needed for these tumors is ipsilateral Horner syndrome. PMID- 26159369 TI - Large-scale freestanding nanometer-thick graphite pellicles for mass production of nanodevices beyond 10 nm. AB - Extreme ultraviolet lithography (EUVL) has received much attention in the semiconductor industry as a promising candidate to extend dimensional scaling beyond 10 nm. We present a new pellicle material, nanometer-thick graphite film (NGF), which shows an extreme ultraviolet (EUV) transmission of 92% at a thickness of 18 nm. The maximum temperature induced by laser irradiation (lambda = 800 nm) of 9.9 W cm(-2) was 267 degrees C, due to the high thermal conductivity of the NGF. The freestanding NGF was found to be chemically stable during annealing at 500 degrees C in a hydrogen environment. A 50 * 50 mm large area freestanding NGF was fabricated using the wet and dry transfer (WaDT) method. The NGF can be used as an EUVL pellicle for the mass production of nanodevices beyond 10 nm. PMID- 26159370 TI - The Specificity of the WINROP Algorithm Can Be Significantly Increased by Reassessment of the WINROP Alarm. AB - BACKGROUND: Retinopathy of prematurity (ROP) is a sight-threatening disease affecting extremely preterm infants. The introduction of new ROP screening surveillance systems, with higher sensitivity and specificity than established ROP screening guidelines, has the potential to reduce the number of stressful eye examinations in these infants. OBJECTIVES: To improve the specificity of the WINROP (Weight, Insulin-like growth factor-I, Neonatal, ROP) surveillance system, identifying extremely preterm infants requiring treatment for ROP. METHODS: Two cohorts that had previously been subjected to WINROP analyses were included and reevaluated in this study. The weight at WINROP alarm for extremely preterm infants, born at gestational age <27 weeks, was reevaluated and by establishing 'safe' WINROP alarm weight limits, an intersample reassessment of WINROP alarm was performed. The two cohorts were as follows: (1) the Extremely Preterm Infants in Sweden Study (EXPRESS) cohort, infants born in Sweden during 2004-2007 (n = 407), and (2) extremely preterm infants in a North American cohort, born during 2006-2009 (n = 566). RESULTS: In the EXPRESS cohort, 12.5% (40/319) of the infants who previously received a WINROP alarm were now reassessed as having no alarm; the specificity of WINROP in EXPRESS increased from 23.9% (86/360) to 35.0% (126/360). In the North American cohort, 15.4% (81/526) were reassessed as having no alarm; the specificity increased from 8.5% (38/447) to 26.6% (119/447). The sensitivity persisted as 97.5% in EXPRESS (45/47) and 98.3% (117/119) in the North American cohort. CONCLUSIONS: The specificity of the WINROP surveillance system for extremely preterm infants can be significantly improved by reassessment using the weight at WINROP alarm. PMID- 26159371 TI - The CAT: A Gender-Inclusive Measure of Controlling and Abusive Tactics. AB - Research has consistently found that partner violence, defined as physical abuse between married, cohabitating, or dating partners, is not the only type of abuse with long-term deleterious effects on victims. Male and female victims alike report that emotional abuse, along with controlling behaviors, are often as or more traumatic. Existing instruments used to measure emotional abuse and control have either been limited to male-perpetrated behaviors, as conceived in the well known Duluth "Power and Control" wheel, or field tested on dating or general population samples. This study discusses the genesis and evolution of a gender inclusive instrument, the Controlling and Abusive Tactics (CAT) Questionnaire, which was field tested on males and females with both a clinical and general population sample. For perpetration, a preliminary comparison across gender found no significant differences across gender for the great majority of items, with women reporting significantly higher rates on 9 items, and men reporting significantly higher rates on 6 items. Women reported higher rates of received abuse than men on 28 of 30 items in which gender differences were found to be significant, but both males and females reported higher victimization than perpetration rates on all items. Exploratory and confirmatory factor analyses resulted in the CAT-2, a valid and reliable instrument appropriate for clinical use by treatment providers as well as for research purposes. PMID- 26159372 TI - Multisensory integration in children with Developmental Coordination Disorder. AB - This study examines how multisensory stimuli affect the performance of children with Developmental Coordination Disorder (DCD) on a choice reaction time (CRT) task. Ten children with DCD, identified using the Movement Assessment Battery for Children-2, aged 7-10 years (4F, M=8 y 3 m, SD=17 m) and 10 typically developing peers (TDC) (5F, M=8 y 4 m, SD=17 m) reached to unimodal (auditory (AO), visual (VO)) and bimodal (audiovisual (AV)) stimuli at one of three target locations. A multisensory (AV) stimulus reduced RTs for both groups (p<0.001, eta(2)=0.36). While the children with DCD had a longer RT in all conditions, the AV stimulus produced RTs in children with DCD (494 ms) that were equivalent to those produced by the TDC to the VO stimulus (493 ms). Movement Time (DCD=486 ms; TDC=434 ms) and Path Length (DCD=25.6 cm; TDC=24.2 cm) were longer in children with DCD compared to TDC as expected (p<0.05). Only the TDC benefited from the AV information for movement control, as deceleration time of the dominant hand was seen to decrease when moving to an AV stimulus (p<0.05). Overall, data shows children with DCD do benefit from a bimodal stimulus to plan their movement, but do not for movement control. Further research is required to understand if this is a result of impaired multisensory integration. PMID- 26159373 TI - Adeno-Associated Virus (AAV) Mediated Dystrophin Gene Transfer Studies and Exon Skipping Strategies for Duchenne Muscular Dystrophy (DMD). AB - Duchenne muscular dystrophy (DMD), an X-linked inherited musclewasting disease primarily affecting young boys with prevalence of between1:3,500- 1:5,000, is a rare genetic disease caused by defects in the gene for dystrophin. Dystrophin protein is critical to the stability of myofibers in skeletal and cardiac muscle. There is currently no cure available to ameliorate DMD and/or its patho physiology. A number of therapeutic strategies including molecular-based therapeutics that replace or correct the missing or nonfunctional dystrophin protein have been devised to correct the patho-physiological consequences induced by dystrophin absence. We will review the current in vivo experimentation status (including preclinical models and clinical trials) for two of these approaches, namely: 1) Adeno-associated virus (AAV) mediated (micro) dystrophin gene augmentation/ supplementation and 2) Antisense oligonucleotide (AON)-mediated exon skipping strategies. PMID- 26159374 TI - Malignant Triton Tumor of the Kidney. New Location Not Previously Reported. AB - Malignant triton tumor (MTT) is a variant of the peripheral nerve sheath tumor. It is very uncommon but shows an aggressive course and limited survival. Half of the cases present symptoms related to neurofibromatosis type 1 disease. There is no standardized treatment, but multimodal approach is the best option. We present the case of a primary MTT located in the kidney, in a 43-year-old woman who received neoadjuvant chemotherapy as first-line treatment followed by surgical resection and adjuvant chemotherapy. PMID- 26159375 TI - Comparative efficacy and safety of daclatasvir/asunaprevir versus IFN-based regimens in genotype 1b hepatitis C virus infection. AB - AIM: Efficacy and safety comparison of daclatasvir/asunaprevir (DCV + ASV) versus peginterferon-alpha/ribavirin (A/R) alone or combined with telaprevir, boceprevir, simeprevir or sofosbuvir in chronic genotype 1b hepatitis C virus infection. METHODS: Network meta-analysis (NMA) and matching-adjusted indirect comparisons (MAICs). RESULTS: Among treatment-naive patients, DCV + ASV demonstrated higher sustained virologic response (SVR) rates than telaprevir + A/R, boceprevir + A/R and A/R in NMA and MAICs and simeprevir + A/R in NMA. DCV + ASV among treatment-experienced patients had higher SVR rates than telaprevir + A/R, boceprevir + A/R, simeprevir + A/R and A/R in MAICs. DCV + ASV had lower adverse events rates than comparators. CONCLUSION: DCV + ASV demonstrated superior efficacy and safety compared with A/R-based regimens. PMID- 26159376 TI - Controlling the flexibility and single-crystal to single-crystal interpenetration reconstitution of metal-organic frameworks. AB - By changing the ligand substituent groups near the open metal sites from hydrophilic to hydrophobic, the guest-induced structural dynamism of a series of isostructural 5-fold interpenetrated MOFs changed from interpenetration reconstitution to simple framework breathing. PMID- 26159377 TI - Review on technological and scientific aspects of feruloyl esterases: A versatile enzyme for biorefining of biomass. AB - With increasing focus on sustainable energy, bio-refining from lignocellulosic biomass has become a thrust area of research. With most of the works being focused on biofuels, significant efforts are also being directed towards other value added products. Feruloyl esterases (EC. 3.1.1.73) can be used as a tool for bio-refining of lignocellulosic material for the recovery and purification of ferulic acid and related hydroxycinnamic acids ubiquitously found in the plant cell wall. More and more genes coding for feruloyl esterases have been mined out from various sources to allow efficient enzymatic release of ferulic acid and allied hydroxycinnamic acids (HCAs) from plant-based biomass. A sum up on enzymatic extraction of HCAs and its recovery from less explored agro residual by products is still a missing link and this review brushes up the achieved landmarks so far in this direction and also covers a detailed patent search on this biomass refining enzyme. PMID- 26159378 TI - Effects of pre-fermentation and pulsed-electric-field treatment of primary sludge in microbial electrochemical cells. AB - The aim of this study was to investigate the combination of two technologies - pulsed electric field (PEF) pre-treatment and semi-continuous pre-fermentation of primary sludge (PS) - to produce volatile fatty acids (VFAs) as the electron donor for microbial electrolysis cells (MECs). Pre-fermentation with a 3-day solids retention time (SRT) led to the maximum generation of VFAs, with or without pretreatment of the PS through pulsed-electric-fields (PEF). PEF treatment before fermentation enhanced the accumulation of the preferred VFA, acetate, by 2.6-fold. Correspondingly, MEC anodes fed with centrate from 3-day pre-fermentation of PEF-treated PS had a maximum current density ~3.1 A/m(2), which was 2.4-fold greater than the control pre-fermented centrate. Over the full duration of batch MEC experiments, using pre-fermented centrate led to successful performance in terms of Coulombic efficiency (95%), Coulombic recovery (80%), and COD-removal efficiency (85%). PMID- 26159379 TI - Lipid production on free fatty acids by oleaginous yeasts under non-growth conditions. AB - Microbial lipids produced by oleaginous yeasts serve as promising alternatives to traditional oils and fats for the production of biodiesel and oleochemicals. To improve its techno-economics, it is pivotal to use wastes and produce high quality lipids of special fatty acid composition. In the present study, four oleaginous yeasts were tested to use free fatty acids for lipid production under non-growth conditions. Microbial lipids of exceptionally high fatty acid relative contents, e.g. those contained over 70% myristic acid or 80% oleic acid, were produced that may be otherwise inaccessible by growing cells on various carbon sources. It was found that Cryptococcus curvatus is a robust strain that can efficiently use oleic acid as well as even-numbered saturated fatty acids with carbon atoms ranging from 10 to 20. Our results provided new opportunity for the production of functional lipids and for the exploitation of organic wastes rich in free fatty acids. PMID- 26159380 TI - Performance of rapid HIV-1/HIV-2 INSTI on plasma and capillary blood for serological diagnosis of non B subtypes and circulating recombinant forms of HIV 1 in Gabon. PMID- 26159381 TI - Alcohol and disease prevention. PMID- 26159382 TI - A new universal simplified adhesive: 36-Month randomized double-blind clinical trial. AB - STATEMENT OF THE PROBLEM: It is still debatable which technique should be used with universal adhesives, either etch-and-rinse (wet or dry) or self-etch strategy (with or without selective enamel etching). PURPOSE OF THE STUDY: To evaluate the 36-month clinical performance of Scotchbond Universal Adhesive (SU, 3M ESPE) in non-carious cervical lesions (NCCLs) using two evaluation criteria. METHODS/MATERIALS: Thirty-nine patients participated in this study. Two-hundred restorations were assigned to four groups: ERm: etch-and-rinse+moist dentin; ERd: etch-and-rinse+dry dentin; Set: selective enamel etching; and SE: self-etch. The same composite resin was inserted for all restorations in up to 3 increments. The restorations were evaluated at baseline and at 6-, 18-, and 36-months using both the FDI and the USPHS criteria. Statistical analyses were performed with Friedman repeated measures ANOVA by rank and McNemar test for significance in each pair (alpha=0.05). RESULTS: Eight restorations (ERm: 1; ERd: 1; Set: 1 and SE: 5) were lost after 36 months, but only significant for SE when compared with baseline (p=0.02 for either criteria). Marginal staining occurred in 6.8% of the restorations (groups ERm, ERd, and Set) and 17.5% of the restorations (group SE), with significant difference for each group when compared with baseline using the FDI criteria (p<0.04), while statistical significance was reached only for SE when compared with baseline using the USPHS criteria (p<0.03). Twenty-eight and 49 restorations were scored as bravo for marginal adaptation using the USPHS and FDI criteria, respectively, with significant difference for each group when compared with baseline (p<0.05). CONCLUSIONS: While there was no statistical difference among bonding strategies when a universal adhesive was used, there were signs of degradation when the universal adhesive was applied in SE mode. The FDI criteria remain more sensitive than the USPHS criteria, especially for the criteria marginal staining and marginal adaptation. PMID- 26159383 TI - Clinical performance of CEREC AC Bluecam conservative ceramic restorations after five years--A retrospective study. AB - OBJECTIVES: The aim of this study was to assess the clinical performance of CAD/CAM partial coverage posterior restorations made by CEREC AC Bluecam system after 5 years. METHODS: 159 ceramic partial coverage posterior restorations were placed in 109 patients in a private practice. The restorations were made using CEREC AC Bluecam with CEREC Blocs or Empress CAD blocks. The clinical performance of the restorations was evaluated with modified California Dental Association (CDA) guidelines, gingival and plaque indices, probing pocket depth, and bleeding on probing in a period of 5 years. Patients' satisfaction was assessed using visual analogue scale. The Kaplan-Meier method was used to analyze survival probability of the restorations (alpha=0.05). RESULTS: The restorations included 102CEREC Blocs and 57 Empress CAD. The survival rates of CEREC Blocs and Empress CAD blocks were 96.0% and 94.6%, respectively (P=0.67). A total of 7 (4.5%) failures were found. The failures were not significantly influenced by restoration size, type and position of teeth. The ceramic fracture was significantly more in nonvital teeth (P=0.04). The periodontal parameters were not significantly different between the restored and control teeth except plaque index. The mean score of patients' satisfaction was 94.4 +/- 8.1. CONCLUSIONS: Chair-side CEREC AC ceramic partial coverage posterior restorations were clinically successful restorations with mean survival rate of 95.5% after 5 years. CLINICAL SIGNIFICANCE: Conservative chair-side CAD/CAM ceramic restorations with less reduction of tooth structure can be a successful restorative method with acceptable survival rate and patient's satisfaction. PMID- 26159384 TI - A clinical, randomized, controlled study on the use of desensitizing agents during tooth bleaching. AB - OBJECTIVES: To evaluate the efficacy of experimental proposals of desensitizing agents during tooth bleaching. METHODS: 140 participants without tooth sensitivity (TS) received 16% carbamide peroxide (14 days-04 h each) (T1) or 35% hydrogen peroxide (single session-45 min) (T2). Participants used concomitantly (10 per group): desensitizing dentifrices (D1-experimental bioactive glass ceramic; D2-commercial potassium nitrate; D3-commercial calcium and sodium phosphosilicate) in-home, daily and, desensitizing pastes (D4-experimental bioactive glass-ceramic; D5-experimental Bioglass type 45S5; D6-commercial calcium phosphate), in-office, immediately after the treatment and more 4 times. Participants in the control group did not use any desensitizing agent. We assessed TS with Visual Analogue Scale. Assessment point 1 was immediately after the first participant's exposure to the treatments; and points 2, 3, 4, and 5 were every 72 h along the period of the study. Two-way ANOVA (considering time and desensitizing as factors) and post-hoc Tukey test (alpha=0.05) analyzed the data. RESULTS: In the control group treated with 35% hydrogen peroxide, TS increased significantly on assessment points 1 and 2. The participants who used a 5% potassium nitrate dentifrice and in-office experimental pastes did not experience TS because of the 35% in-office bleaching treatment. CONCLUSIONS: TS caused by 35% hydrogen peroxide in-office tooth bleaching was controlled by experimental products prepared as pastes D4-experimental bioactive glass-ceramic and D5-experimental Bioglass type 45S5, but not by D1-experimental dentifrice containing bioactive glass-ceramic. CLINICAL SIGNIFICANCE: There is no a gold standard protocol for TS caused by tooth bleaching. The study of novel desensitizing agents that can obliterate the dentinal tubules in a faster-acting and long-lasting way may help meet this clinical need. PMID- 26159385 TI - Antibacterial effects of cavity lining: a systematic review and network meta analysis. AB - OBJECTIVES: Cavity liners are frequently used prior placing a restoration, with one main aim being to reduce the number of remaining bacteria. We systematically appraised studies comparing antibacterial effects of different liners against each other or no liner. DATA STUDIES: reporting the number of sterile cavities before/after lining or sealing, or the reduction in bacterial numbers (colony forming-units) in two or more treatment groups were included. Treatments were categorized as: no/placebo liner, calcium hydroxide, mineral trioxide aggregate, antibiotic/disinfectant, calcium phosphates, zinc oxide eugenol, black copper cement, and glass ionomer cement liners. Pairwise and network meta-analyses were performed. STUDY SELECTION: From 113 identified studies, 14 (500 treated lesions) were included. Risk of bias was high or unclear. Based on 11 studies, network meta-analysis found mineral trioxide lining to yield the greatest probability of achieving sterile cavities after a lining/sealing period (73%), followed by antibiotic/disinfectant (8%) and zinc oxide eugenol (7%). Only six studies assessed bacterial reduction after lining/sealing, and zinc oxide eugenol was found to have the highest probability of achieving a bacterial reduction. In both analyses, not providing any lining was found to have low antibacterial effects. CONCLUSION: Within the limitations of this review and the included studies, certain liners seem more suitable to achieve sterile cavities or reduce bacterial numbers than others. Given the paucity of data and the unclear impact of remaining bacteria on clinical outcomes, further recommendations for specific cavity treatments prior a restoration are not possible. CLINICAL SIGNIFICANCE: There is insufficient evidence to generally recommend cavity lining or the use of any specific liner based on their antibacterial effects. Dentists might continue to use liners, but should be aware that such use is not strongly supported by clinical studies. PMID- 26159386 TI - Comparison of photopolymerization temperature increases in internal and external positions of composite and tooth cavities in real time: Incremental fillings of microhybrid composite vs. bulk filling of bulk fill composite. AB - OBJECTIVES: This study evaluated temperature increases in the composite and pulpal side of dentin from incremental and bulk fillings in composite restorations. METHODS: Class-1 cavities (5 mm * 4 mm * 3 mm) were prepared in ten extracted third molars, filled with composite, and restored with two separate horizontal layers of Filtek Z250 (3M ESPE) in the incremental group or a single layer of SureFil SDR Flow (Dentsply) in the bulk-fill group (n=5). After placing the specimens in a 36.5 degrees C water bath, temperatures were measured with eight thermocouples at the bottom center (BC), middle center (MC), top center (TC), bottom corner (BE), middle corner (ME), and top corner (TE) of the cavity, at the pulpal side of the dentin within the pulp chamber (PD), and in the curing light (CL) tip during light curing at 750 mW/cm(2) for 20s and then analyzed with one-way analysis of variance and Tukey's HSD tests (alpha=0.01). RESULTS: Maximum temperatures ranged from 39.0 degrees C (PD 1st increment) to 60.0 degrees C (MC 1st increment) in the incremental group and from 42.0 degrees C (PD) to 74.9 degrees C (TC) in the bulk-fill group. In the incremental group, temperatures were similar between the 1st and 2nd increments, except at MC and BC. CONCLUSIONS: Bulk-fill group exhibited a greater increase in temperature during composite restoration. Regardless of the filling technique, more heat was generated at the center than at the corner and at the top than at the bottom of the composite. PD temperatures increased by 3.1 degrees C and 5.5 degrees C in the incremental group and bulk-fill group, respectively. CLINICAL SIGNIFICANCE: Although bulk fillings save clinical chair time, clinicians should be aware of the greater heat that is generated with increasing amounts of composites during polymerization, which can jeopardize the pulpal health, especially when a large and deep cavity is being restored. PMID- 26159387 TI - Investigating the Role of the Posttranscriptional Gene Regulator MiR-24- 3p in the Proliferation, Migration and Apoptosis of Human Arterial Smooth Muscle Cells in Arteriosclerosis Obliterans. AB - AIMS: To explore the expression of miR-24-3p in human arteries with arteriosclerosis obliterans (ASO) as well as the role of miR-24-3p in the pathogenesis of ASO. METHODS: We used quantitative real-time PCR (qRT-PCR) and in situ hybridization to monitor miR-24-3p expression in human arteries. To investigate the effect of miR-24-3p on human arterial smooth muscle cells (HASMCs), we applied cell counting and EdU assays to monitor proliferation and transwell and wound healing assays to investigate migration and flow cytometry to investigate apoptosis. Furthermore, we applied 3'-untranslated region (3'-UTR) luciferase assays to investigate the role of miR-24-3p in targeting platelet derived growth factor receptor B (PDGFRB) and c-Myc. RESULTS: MiR-24-3p was mainly located in the media of arteries and was downregulated in ASO arteries compared with normal arteries. Platelet-derived growth factor BB (PDGF-BB) treatment reduced the expression of miR-24-3p in primary cultured HASMCs. MiR-24 3p mimic oligos inhibited the proliferation and migration, and promotes apoptosis of HASMCs. Our 3'-UTR luciferase assays confirmed that PDGFRB and c-Myc were targets of miR-24-3p. CONCLUSION: The results suggest that miR-24-3p regulates the proliferation and migration of HASMCs by targeting PDGFRB and c-Myc. The PDGF/miR-24-3p/PDGFRB and PDGF/miR-24-3p/c-Myc pathways may play critical roles in the pathogenesis of ASO. These findings highlight the potential for new therapeutic targets for ASO. PMID- 26159388 TI - Resection of Obstructive Left-Sided Colon Cancer at a National Level: A Prospective Analysis of Short-Term Outcomes in 1,816 Patients. AB - BACKGROUND/AIMS: The prematurely closed Stent-In II trial in patients with left sided obstructive colon cancer may have influenced clinical decision making in The Netherlands. The aim of this study was to evaluate treatment of left-sided malignant colon obstruction at a population level since then. METHODS: Short-term outcomes of all patients who underwent resection for left-sided obstructive colon cancer between 2009 and 2012 were assessed based on a prospective national registry. RESULTS: In total, 1,816 evaluable patients were included; acute resection was performed in 1,485 (81.8%), and endoscopic stent or decompressing stoma followed by resection in 196 (10.8%) and 135 (7.4%), respectively. The use of endoscopic stenting significantly decreased from 18% (2009) to 6% (2012). Overall 30-day or in-hospital mortality rate was 6.9, 5.6, and 3.7%, respectively (p = 0.107). Mortality rate after acute resection was 2.9% in patients <70 [corrected] years, but mortality rates up to 32.2% were observed in high-risk elderly patients. CONCLUSION: Acute resection as first choice treatment seems justified for patients <70 [corrected] years of age given a mortality rate of 3%. For the elderly frail patients, mortality rates over 30% after acute resection stress the need for alternative treatment strategies. PMID- 26159389 TI - Modulation of hematopoietic progenitor cell fate in vitro by varying collagen oligomer matrix stiffness in the presence or absence of osteoblasts. AB - To recreate the in vivo hematopoietic cell microenvironment or niche and to study the impact of extracellular matrix (ECM) biophysical properties on hematopoietic progenitor cell (HPC) proliferation and function, mouse bone-marrow derived HPC (Lin-Sca1+cKit+/(LSK) were cultured within three-dimensional (3D) type I collagen oligomer matrices. To generate a more physiologic milieu, 3D cultures were established in both the presence and absence of calvariae-derived osteoblasts (OB). Collagen oligomers were polymerized at varying concentration to give rise to matrices of different fibril densities and therefore matrix stiffness (shear storage modulus, 50-800 Pa). Decreased proliferation and increased clonogenicity of LSK cells was associated with increase of matrix stiffness regardless of whether OB were present or absent from the 3D culture system. Also, regardless of whether OB were or were not added to the 3D co-culture system, LSK within 800 Pa collagen oligomer matrices maintained the highest percentage of Lin-Sca1+ cells as well as higher percentage of cells in quiescent state (G0/G1) compared to 50 Pa or 200Pa matrices. Collectively, these data illustrate that biophysical features of collagen oligomer matrices, specifically fibril density-induced modulation of matrix stiffness, provide important guidance cues in terms of LSK expansion and differentiation and therefore maintenance of progenitor cell function. PMID- 26159390 TI - Repeated fine-needle aspiration of solid tumours in mice allows the identification of multiple infiltrating immune cell types. AB - This paper describes a novel method for following the changes in mouse tumour infiltrating immune cell populations by repeated sampling of tumours by fine needle aspiration (FNA), followed by flow cytometry. Using this technique we were able to collect samples from P815 mouse mastocytomas, and identify and enumerate six tumour-infiltrating immune cell types at multiple time points for each mouse. We demonstrate good agreement between cell percentages obtained from FNA samples and matched whole tumour digests (WTDs). We also demonstrate that neither survival nor the incidence of liver metastasis is adversely affected by the procedure. Our method has a clear advantage over the common practice of sacrificing mice and collecting tissue at pre-determined time points, as the technique allows 1) repeated sampling of each mouse over time, thus many fewer mice are required, and 2) the correlation of survival data with tumour infiltrating immune cell types at different time points. This potentially allows immune cell types associated with increased or decreased survival to be identified. Therefore, our technique should greatly facilitate the characterisation of anti-tumour immunity induced in response to cancer therapy in small animal models. PMID- 26159391 TI - Faith-based organisations bolster health care in Rwanda. PMID- 26159392 TI - Controversies in faith and health care. AB - Differences in religious faith-based viewpoints (controversies) on the sanctity of human life, acceptable behaviour, health-care technologies and health-care services contribute to the widespread variations in health care worldwide. Faith linked controversies include family planning, child protection (especially child marriage, female genital mutilation, and immunisation), stigma and harm reduction, violence against women, sexual and reproductive health and HIV, gender, end-of-life issues, and faith activities including prayer. Buddhism, Christianity, Hinduism, Islam, Judaism, and traditional beliefs have similarities and differences in their viewpoints. Improved understanding by health-care providers of the heterogeneity of viewpoints, both within and between faiths, and their effect on health care is important for clinical medicine, public-health programmes, and health-care policy. Increased appreciation in faith leaders of the effect of their teachings on health care is also crucial. This Series paper outlines some faith-related controversies, describes how they influence health care provision and uptake, and identifies opportunities for research and increased interaction between faith leaders and health-care providers to improve health care. PMID- 26159393 TI - The view from above: faith and health. PMID- 26159394 TI - Strengthening of partnerships between the public sector and faith-based groups. AB - The sharpening focus on global health and the growing recognition of the capacities and scope of faith-based groups for improving community health outcomes suggest an intentional and systematic approach to forging strong, sustained partnerships between public sector agencies and faith-based organisations. Drawing from both development and faith perspectives, this Series paper examines trends that could ground powerful, more sustainable partnerships and identifies new opportunities for collaboration based on respective strengths and existing models. This paper concludes with five areas of recommendations for more effective collaboration to achieve health goals. PMID- 26159396 TI - Faith-based delivery of science-based care. PMID- 26159395 TI - Religion and Ebola: learning from experience. PMID- 26159397 TI - Avraham Steinberg: leading light in faith-based medical ethics. PMID- 26159398 TI - Understanding the roles of faith-based health-care providers in Africa: review of the evidence with a focus on magnitude, reach, cost, and satisfaction. AB - At a time when many countries might not achieve the health targets of the Millennium Development Goals and the post-2015 agenda for sustainable development is being negotiated, the contribution of faith-based health-care providers is potentially crucial. For better partnership to be achieved and for health systems to be strengthened by the alignment of faith-based health-providers with national systems and priorities, improved information is needed at all levels. Comparisons of basic factors (such as magnitude, reach to poor people, cost to patients, modes of financing, and satisfaction of patients with the services received) within faith-based health-providers and national systems show some differences. As the first report in the Series on faith-based health care, we review a broad body of published work and introduce some empirical evidence on the role of faith based health-care providers, with a focus on Christian faith-based health providers in sub-Saharan Africa (on which the most detailed documentation has been gathered). The restricted and diverse evidence reported supports the idea that faith-based health providers continue to play a part in health provision, especially in fragile health systems, and the subsequent reports in this Series review controversies in faith-based health care and recommendations for how public and faith sectors might collaborate more effectively. PMID- 26159399 TI - Physiology and proteomics research on the leaves of ancient Platycladus orientalis (L.) during winter. AB - Ancient trees have an important value in humanities and history, and also have an important scientific value in the investigation of the decline and senescence mechanisms. Thus, we conducted an environmental stress study using ancient trees. To evaluate age-dependent changes in physiology and the leaf proteome, we assessed the low-temperature stress responses of 20 +/- 5-, 500 +/- 100- and 1200 +/- 200-year-old Platycladus orientalis (L.) samples obtained outdoors during winter. Several physiological parameters were evaluated. Leaf proteomes were obtained using two-dimensional electrophoresis gels, and 77 protein spots were identified successfully using MALDI TOF/TOF MS/MS. The majority of the identified protein species were classified into functional categories including defense/stress-related, energy and carbohydrate metabolism, photosynthesis, and hormone-related functions. A general reduction in the abundance of protein species was observed as the age of the studied trees increased; reduction in photosynthesis and defense/stress-related categories were particularly apparent in the leaves of ancient trees. However, the number of protein species with functions in energy and carbohydrate metabolism increased with age. An increase in the abundance of lipid metabolism and hormone-related protein species was a primary characteristic of the leaves of ancient trees under low-temperature stress during winter. These results improve our understanding of the biochemical mechanisms of stress responses in ancient trees. BIOLOGICAL SIGNIFICANCE: Low temperature is the most common meteorological challenge in the study area. For evergreen plants, low-temperature stress has a great impact on the leaves of ancient P. orientalis. Thus, we conducted an environmental stress study using ancient trees. Recently, various studies were carried out in ancient trees. However, no information is available on the molecular mechanisms of defense to low-temperature stress in ancient trees. Therefore, this original study comprises the following differential proteomic analysis of ancient P. orientalis: (1) age dependent changes in the physiology and leaf proteome are evaluated under low temperature stress to (2) understand the differences in metabolic responses between ancient and adult trees under low-temperature stress during winter. This analysis will provide an understanding of the complex physiological changes that occur in ancient trees. The results suggest that certain identified proteins can be used as markers of low-temperature stress in ancient P. orientalis. PMID- 26159400 TI - Jaundice as a Rare Indication for Aortic Aneurysm Repair. AB - Compression of adjacent anatomic structures by an abdominal aortic aneurysm (AAA) can result in a variety of symptoms. We describe the case of an 88-year-old Caucasian woman with jaundice, elevated laboratory parameters for extrahepatic and intrahepatic cholestasis, and concomitant juxtarenal AAA compressing the liver hilum. Following exclusion of other common causes for cholestasis, the patient was considered to have a symptomatic AAA. Open abdominal aortic surgery revealed a contained rupture and was repaired. Obstructive jaundice secondary to a compromising AAA is a rare condition and to the best of our knowledge has not been reported to date. PMID- 26159401 TI - [Retinal vascular occlusions in Lome]. PMID- 26159402 TI - [Optic neuritis: Rare manifestation of neurobrucellosis]. PMID- 26159403 TI - Isolation of a novel LPS-induced component of the ML superfamily in Ciona intestinalis. AB - ML superfamily represents a group of proteins playing important roles in lipid metabolism and innate immune response. In this study, we report the identification of the first component of the ML superfamily in the invertebrate Ciona intestinalis by means of a subtractive hybridization strategy. Sequence homology and phylogenetic analysis showed that this protein forms a specific clade with vertebrate components of the Niemann-Pick type C2 protein and, for this reason, it has been named Ci-NPC2. The putative Ci-NPC2 is a 150 amino acids long protein with a short signal peptide, seven cysteine residues, three putative lipid binding site and a three-dimensional model showing a characteristic beta strand structure. Gene expression analysis demonstrated that the Ci-NPC2 protein is positively upregulated after LPS inoculum with a peak of expression 1 h after challenge. Finally, in-situ hybridization demonstrated that the Ci-NPC2 protein is preferentially expressed in hemocytes inside the vessel lumen. PMID- 26159404 TI - A specific cathepsin-L-like protease purified from an insect midgut shows antibacterial activity against gut symbiotic bacteria. AB - Because gut symbiotic bacteria affect host biology, host insects are expected to evolve some mechanisms for regulating symbiont population. The bean bug, Riptortus pedestris, harbors the Burkholderia genus as a gut symbiont in the midgut organ, designated as the M4 region. Recently, we demonstrated that the lysate of M4B, the region adjacent to M4, harbors potent antibacterial activity against symbiotic Burkholderia but not to cultured Burkholderia. However, the bona fide substance responsible for observed antibacterial activity was not identified in the previous study. Here, we report that cathepsin-L-like protease purified from the lysate of M4B showed strong antibacterial activity against symbiotic Burkholderia but not the cultured Burkholderia. To further confirm this activity, recombinant cathepsin-L-like protease expressed in Escherichia coli also showed antibacterial activity against symbiotic Burkholderia. These results suggest that cathepsin-L-like protease purified from the M4B region plays a critical role in controlling the population of the Burkholderia gut symbiont. PMID- 26159405 TI - Single-tube nested PCR assay for the detection of avian botulism in cecal contents of chickens. AB - This paper describes a novel diagnostic method for the detection of avian botulism caused by Clostridium botulinum type C and C/D, using single-tube nested PCR assay. This assay was developed to overcome the disadvantages of bioassays used in experiments with mice. Three primer pairs including an antisense primer were designed to target the N-terminal of the toxin gene from C. botulinum types C and C/D. The specificity of the PCR assay was confirmed by using 33 bacterial strains and chicken cecal contents from farms that experienced botulism outbreaks. The detection limit for purified DNA was 1.1 fg/MUl, and for bacterial spores was 4.3 spores/200 mg of cecal contents. While checking for specificity of the PCR assay, the reactions with the templates form C. botulinum type C and C/D which were tested became positive, but the rest of the reactions turned negative. However, the results for all clinical samples (n = 8) were positive. The PCR assay results for cecal samples obtained from 300 healthy chickens (150 Korean native chickens and 150 broilers) were all negative. This assay is rapid and straightforward and evades ethical issues associated with mouse bioassay. Moreover, it is more economical than real-time PCR. PMID- 26159406 TI - The detection of Dichelobacter nodosus and Fusobacterium necrophorum from ovine footrot in Kashmir, India. AB - In a study conducted, a total of 450 swab samples from footrot lesions of naturally infected sheep were collected in all the ten districts of the Kashmir valley and were examined for the presence of Dichelobacter nodosus (D. nodosus) and Fusobacterium necrophorum (F. necrophorum), in order to determine if F. necrophorum was associated with ovine footrot. The detection of F. necrophorum and D. nodosus was carried out by polymerase chain reaction targeting the leukotoxin (lktA) and 16S rRNA genes, respectively. In this study, only less than 50% of positive samples contained both the bacteria, so it is not possible to conclude with certainty that both bacteria are together required for the disease manifestation. PMID- 26159407 TI - Predicting loss of lung function in healthy people. PMID- 26159410 TI - Did AIDS mortality decrease the number of lifetime sexual partners in Kenya: an ecological analysis? AB - We assessed if there has been a decline in the median number of reported lifetime sexual partners in Kenya following the AIDS epidemic. The Wilcoxon rank-sum test was used to compare the median and interquartile range (IQR) of the number of lifetime sexual partners for men aged 20-54 years in the 1993 and 2008 Kenyan Demographic Health Surveys. The median number of sexual partners in 1993 increased rapidly to 10 partners reported at age 30 years then plateaued at this level. In 2008, the median number of sexual partners plateaued at around half the value of the 1993 plateau. The median number of lifetime sexual partners for men aged 20-54 years declined from 10 (IQR 4-20) in 1993 to 3 (IQR 2-7) in 2008 (P < 0.001). This decline could be due to a combination of the effects of AIDS mortality and a misreporting bias. PMID- 26159409 TI - Troponin T-release associates with cardiac radiation doses during adjuvant left sided breast cancer radiotherapy. AB - BACKGROUND: Adjuvant radiotherapy (RT) for left-sided breast cancer increases cardiac morbidity and mortality. For the heart, no safe radiation threshold has been established. Troponin T is a sensitive marker of myocardial damage. Our aim was to evaluate the effect of left-sided breast cancer RT on serum high sensitivity troponin T (hscTnT) levels and its association with cardiac radiation doses and echocardiographic parameters. METHODS: A total of 58 patients with an early stage, left-sided breast cancer or ductal carcinoma in situ (DCIS) who received adjuvant breast RT without prior chemotherapy were included in this prospective, non-randomized study. Serum samples were taken before, during and after RT. An increase of hscTnT >30 % was predefined as significant. A comprehensive 2D echocardiograph and electrocardiogram (ECG) were performed before and after RT. Dose-volume histograms (DVHs) were generated for different cardiac structures. RESULTS: The hscTnT increased during RT from baseline in 12/58 patients (21 %). Patients with increased hscTnT values (group A, N = 12) had significantly higher radiation doses for the whole heart (p = 0.02) and left ventricle (p = 0.03) than patients without hscTnT increase (group B, N = 46). For the left anterior descending artery (LAD), differences between groups A and B were found in volumes receiving 15 Gy (p = 0.03) and 20 Gy (p = 0.03) Furthermore, after RT, the interventricular septum thickened (p = 0.01), and the deceleration time was prolonged (p = 0.008) more in group A than in group B. CONCLUSIONS: The increase in hscTnT level during adjuvant RT was positively associated with the cardiac radiation doses for the whole heart and LV in chemotherapy-naive breast cancer patients. Whether these acute subclinical changes increase the risk of excessive long-term cardiovascular morbidity or mortality, will be addressed in the follow-up of our patients. PMID- 26159411 TI - Corrigendum to "Magnetic resonance beacon to detect intracellular microRNA during neurogenesis" [Biomaterials 41 (2015) 69-78]. PMID- 26159408 TI - Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study. AB - BACKGROUND: Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population. METHODS: We assessed longitudinal data on CC16 concentrations in serum and associations with decline in FEV1 and incidence of airflow limitation for adults who were free from COPD at baseline in the population-based Tucson Epidemiological Study of Airway Obstructive Disease ([TESAOD] n=960, mean follow up 14 years), European Community Respiratory Health Survey ([ECRHS-Sp] n=514, 11 years), and Swiss Cohort Study on Air Pollution and Lung Diseases in Adults ([SAPALDIA] n=167, 8 years) studies. Additionally, we measured circulating CC16 concentrations in samples from children aged 4-6 years in the Tucson Children's Respiratory Study (n=427), UK Manchester Asthma and Allergy Study (n=481), and the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (n=231) birth cohorts to assess whether low CC16 concentrations in childhood were predictive for subsequent lung function. FINDINGS: After adjustment for sex, age, height, smoking status and intensity, pack-years, asthma, and FEV1 at baseline, we found an inverse association between CC16 concentration and decline in FEV1 in adults in TESAOD (4.4 mL/year additional FEV1 decline for each SD decrease in baseline CC16 concentration, p=0.0014) and ECRHS-Sp (2.4 mL/year, p=0.023); the effect in SAPALDIA was marginal (4.5 mL/year, p=0.052). Low CC16 concentration at baseline was also associated with increased risk of incident stage 2 airflow limitation (ratio of FEV1 to forced expiratory volume [FEV1/FVC] less than 70% plus FEV1 % predicted less than 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 concentrations was associated with a subsequent FEV1 deficit of 68 mL up to age 16 years (p=0.0001), which was confirmed in children who had never smoked by age 16 years (-71 mL, p<0.0001). INTERPRETATION: Low concentrations of CC16 in serum are associated with reduced lung function in childhood, accelerated lung function decline in adulthood, and development of moderate airflow limitation in the general adult population. FUNDING: National Heart, Lung, and Blood Institute and European Union Seventh Framework Programme. PMID- 26159412 TI - Survival of planets around shrinking stellar binaries. AB - The discovery of transiting circumbinary planets by the Kepler mission suggests that planets can form efficiently around binary stars. None of the stellar binaries currently known to host planets has a period shorter than 7 d, despite the large number of eclipsing binaries found in the Kepler target list with periods shorter than a few days. These compact binaries are believed to have evolved from wider orbits into their current configurations via the so-called Lidov-Kozai migration mechanism, in which gravitational perturbations from a distant tertiary companion induce large-amplitude eccentricity oscillations in the binary, followed by orbital decay and circularization due to tidal dissipation in the stars. Here we explore the orbital evolution of planets around binaries undergoing orbital decay by this mechanism. We show that planets may survive and become misaligned from their host binary, or may develop erratic behavior in eccentricity, resulting in their consumption by the stars or ejection from the system as the binary decays. Our results suggest that circumbinary planets around compact binaries could still exist, and we offer predictions as to what their orbital configurations should be like. PMID- 26159413 TI - Correction to Supporting Information for Xu et al., Effects of anthropogenic emissions on aerosol formation from isoprene and monoterpenes in the southeastern United States. PMID- 26159414 TI - Correction for Delley et al., Proton transfers are key elementary steps in ethylene polymerization on isolated chromium(III) silicates. PMID- 26159415 TI - Correction for Xu et al., Effects of anthropogenic emissions on aerosol formation from isoprene and monoterpenes in the southeastern United States. PMID- 26159416 TI - Climate change and decadal shifts in the phenology of larval fishes in the California Current ecosystem. AB - Climate change has prompted an earlier arrival of spring in numerous ecosystems. It is uncertain whether such changes are occurring in Eastern Boundary Current Upwelling ecosystems, because these regions are subject to natural decadal climate variability, and regional climate models predict seasonal delays in upwelling. To answer this question, the phenology of 43 species of larval fishes was investigated between 1951 and 2008 off southern California. Ordination of the fish community showed earlier phenological progression in more recent years. Thirty-nine percent of seasonal peaks in larval abundance occurred earlier in the year, whereas 18% were delayed. The species whose phenology became earlier were characterized by an offshore, pelagic distribution, whereas species with delayed phenology were more likely to reside in coastal, demersal habitats. Phenological changes were more closely associated with a trend toward earlier warming of surface waters rather than decadal climate cycles, such as the Pacific Decadal Oscillation and North Pacific Gyre Oscillation. Species with long-term advances and delays in phenology reacted similarly to warming at the interannual time scale as demonstrated by responses to the El Nino Southern Oscillation. The trend toward earlier spawning was correlated with changes in sea surface temperature (SST) and mesozooplankton displacement volume, but not coastal upwelling. SST and upwelling were correlated with delays in fish phenology. For species with 20th century advances in phenology, future projections indicate that current trends will continue unabated. The fate of species with delayed phenology is less clear due to differences between Intergovernmental Panel on Climate Change models in projected upwelling trends. PMID- 26159417 TI - Correction for Lock et al., Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma. PMID- 26159418 TI - Formation of surface nanodroplets under controlled flow conditions. AB - Nanodroplets on a solid surface (i.e., surface nanodroplets) have practical implications for high-throughput chemical and biological analysis, lubrications, laboratory-on-chip devices, and near-field imaging techniques. Oil nanodroplets can be produced on a solid-liquid interface in a simple step of solvent exchange in which a good solvent of oil is displaced by a poor solvent. In this work, we experimentally and theoretically investigate the formation of nanodroplets by the solvent exchange process under well-controlled flow conditions. We find significant effects from the flow rate and the flow geometry on the droplet size. We develop a theoretical framework to account for these effects. The main idea is that the droplet nuclei are exposed to an oil oversaturation pulse during the exchange process. The analysis shows that the volume of the nanodroplets increases with the Peclet number Pe of the flow as ? Pe(3/4), which is in good agreement with our experimental results. In addition, at fixed flow rate and thus fixed Peclet number, larger and less homogeneously distributed droplets formed at less-narrow channels, due to convection effects originating from the density difference between the two solutions of the solvent exchange. The understanding from this work provides valuable guidelines for producing surface nanodroplets with desired sizes by controlling the flow conditions. PMID- 26159419 TI - Correction to Supporting Information for Delley et al., Proton transfers are key elementary steps in ethylene polymerization on isolated chromium(III) silicates. PMID- 26159420 TI - microRNAs and inherited retinal dystrophies. PMID- 26159421 TI - Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression. AB - The available evidence suggests that the lethality of glioblastoma is driven by small subpopulations of cells that self-renew and exhibit tumorigenicity. It remains unclear whether tumorigenicity exists as a static property of a few cells or as a dynamically acquired property. We used tumor-sphere and xenograft formation as assays for tumorigenicity and examined subclones isolated from established and primary glioblastoma lines. Our results indicate that glioblastoma tumorigenicity is largely deterministic, yet the property can be acquired spontaneously at low frequencies. Further, these dynamic transitions are governed by epigenetic reprogramming through the lysine-specific demethylase 1 (LSD1). LSD depletion increases trimethylation of histone 3 lysine 4 at the avian myelocytomatosis viral oncogene homolog (MYC) locus, which elevates MYC expression. MYC, in turn, regulates oligodendrocyte lineage transcription factor 2 (OLIG2), SRY (sex determining region Y)-box 2 (SOX2), and POU class 3 homeobox 2 (POU3F2), a core set of transcription factors required for reprogramming glioblastoma cells into stem-like states. Our model suggests epigenetic regulation of key transcription factors governs transitions between tumorigenic states and provides a framework for glioblastoma therapeutic development. PMID- 26159423 TI - Near-field collimation of light carrying orbital angular momentum with bull's-eye assisted plasmonic coaxial waveguides. AB - The orbital angular momentum (OAM) of light, as an emerging hotspot in optics and photonics, introduces many degrees of freedom for applications ranging from optical communication and quantum processing to micromanipulation. To achieve a high degree of integration, optical circuits for OAM light are essential, which are, however, challenging in the optical regime owing to the lack of well developed theory. Here we provide a scheme to guide and collimate the OAM beam at the micro- and nano-levels. The coaxial plasmonic slit was exploited as a naturally occurring waveguide for light carrying OAM. Concentric grooves etched on the output surface of the coaxial waveguide were utilized as a plasmonic metasurface to couple the OAM beam to free space with greatly increased beam directivity. Experimental results at lambda = 532 nm validated the novel transportation and collimating effect of the OAM beam. Furthermore, dynamic tuning of the topological charges was demonstrated by using a liquid crystal spatial light modulator (SLM). PMID- 26159422 TI - Structural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex. AB - Nonstructural protein 14 (nsp14) of coronaviruses (CoV) is important for viral replication and transcription. The N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping. The molecular basis of both these functions is unknown. Here, we describe crystal structures of severe acute respiratory syndrome (SARS)-CoV nsp14 in complex with its activator nonstructural protein10 (nsp10) and functional ligands. One molecule of nsp10 interacts with ExoN of nsp14 to stabilize it and stimulate its activity. Although the catalytic core of nsp14 ExoN is reminiscent of proofreading exonucleases, the presence of two zinc fingers sets it apart from homologs. Mutagenesis studies indicate that both these zinc fingers are essential for the function of nsp14. We show that a DEEDh (the five catalytic amino acids) motif drives nucleotide excision. The N7-MTase domain exhibits a noncanonical MTase fold with a rare beta-sheet insertion and a peripheral zinc finger. The cap precursor guanosine-P3-adenosine-5',5'-triphosphate and S-adenosyl methionine bind in proximity in a highly constricted pocket between two beta-sheets to accomplish methyl transfer. Our studies provide the first glimpses, to our knowledge, into the architecture of the nsp14-nsp10 complex involved in RNA viral proofreading. PMID- 26159424 TI - Vascular Anomalies Guidelines by the Italian Society for the study of Vascular Anomalies (SISAV). PMID- 26159425 TI - Retrospective assessment of self-reported exposure to medical ionizing radiation: results of a feasibility study conducted in Germany. AB - BACKGROUND: Exposure to medical ionizing radiation has been increasing over the past decades and constitutes the largest contributor to overall radiation exposure in the general population. While occupational exposures are generally monitored by national radiation protection agencies, individual data on medical radiation exposure for the general public are not regularly collected. The aim of this study was to determine the feasibility of assessing lifetime medical ionizing radiation exposure from diagnostic and therapeutic procedures retrospectively and prospectively within the framework of the German National Cohort study. METHODS: Retrospective assessment of individual medical radiation exposure was done using an interviewer-based questionnaire among 199 participants (87 men and 112 women) aged 20-69 randomly drawn from the general population at two recruitment locations in Germany. X-ray cards were distributed to 97 participants at one recruitment center to prospectively collect medical radiation exposure over a 6-month period. The Wilcoxon-Mann-Whitney test was used to test differences in self-reported median examination frequencies for the variables age, sex, and recruitment center. To evaluate the self-reported information on radiological procedures, agreement was assessed using health insurance data as gold standard for the time period 2005 to 2010 from 8 participants. RESULTS: Participants reported a median of 7 lifetime X-ray examinations (interquartile range 4-13), and 42% (n = 83) reported having had a CT scan (2, IQR = 1-3). Women reported statistically significant more X-ray examinations than men. Individual frequencies above the 75th percentile (>=15 X-ray examinations) were predominantly observed among women and in individuals >50 years of age. The prospective exposure assessment yielded a 60% return-rate of X-ray cards (n = 58). 16 (28%) of the returned cards reported radiological examinations conducted during the 6-month period but generally lacked more detailed exposure information. X-ray examinations reported for the period for which health insurance data were available provided a moderately valid measure of individual medical radiation exposure. CONCLUSIONS: The assessment of more recent medical examinations seems in the German National Cohort study feasible, whereas lifetime medical radiation exposure appears difficult to assess via self-reports. Health insurance data may be a potentially useful tool for the assessment of individual data on medical radiation exposure both retrospectively and prospectively. PMID- 26159426 TI - Localization and topology protected quantum coherence at the edge of hot matter. AB - Topological phases are characterized by edge states confined near the boundaries by a bulk energy gap. On raising temperature, these edge states are typically lost due to mobile thermal excitations. However, disorder can localize an isolated many-body system, potentially allowing for a sharply defined topological phase even in a highly excited state. We explicitly demonstrate this in a model of a disordered, one-dimensional magnet with spin one-half edge excitations. Furthermore, we show that the time evolution of a simple, highly excited state reveals quantum coherent edge spins. In particular, we demonstrate the coherent revival of an edge spin over a time scale that grows exponentially with system size. This is in sharp contrast to the general expectation that quantum bits strongly coupled with a hot many-body system will rapidly lose coherence. This result opens new directions in the study of topologically protected quantum dynamics. PMID- 26159427 TI - Computerized Analysis of Vocal Folds Vibration From Laryngeal Videostroboscopy. AB - OBJECTIVES: To develop an objective analysis of laryngeal videostroboscopy (VSS) movies in the space-time domain for quantitative determination of the true vocal folds (TVFs) vibratory pattern to allow for detection of local pathologies at early stages of development. METHODS: Contours of the TVF and false vocal folds (FVFs) were tracked on each frame of a VSS movie. A registration algorithm was used with respect to the centerline of the FVF to eliminate movements not related to TVF vibration. The registered contours of the TVF were analyzed in time and frequency domains. RESULTS: The TVF vibration demonstrated a sinusoidal pattern with the same fundamental frequency at every section along the folds of healthy subjects, as well as detection of an abnormal area with a different fundamental frequency in TVF with local pathologies. Analysis of the TVF vibration time delay of healthy subject revealed a posterior-to-anterior longitudinal wave that was not detected by visual observation. CONCLUSIONS: An objective analysis of laryngeal VSS movies was developed for quantitative determination of the TVF vibration. This analysis was able to detect and quantify TVF characteristics in normal subjects as well as in patients with pathologies beyond the ability of examinee's naked eyes. PMID- 26159428 TI - Iron and hepcidin as risk factors in atherosclerosis: what do the genes say? AB - BACKGROUND: Previous reports suggested a role for iron and hepcidin in atherosclerosis. Here, we evaluated the causality of these associations from a genetic perspective via (i) a Mendelian randomization (MR) approach, (ii) study of association of atherosclerosis-related single nucleotide polymorphisms (SNPs) with iron and hepcidin, and (iii) estimation of genomic correlations between hepcidin, iron and atherosclerosis. RESULTS: Analyses were performed in a general population sample. Iron parameters (serum iron, serum ferritin, total iron binding capacity and transferrin saturation), serum hepcidin and genome-wide SNP data were available for N = 1,819; non-invasive measurements of atherosclerosis (NIMA), i.e., presence of plaque, intima media thickness and ankle-brachial index (ABI), for N = 549. For the MR, we used 12 iron-related SNPs that were previously identified in a genome-wide association meta-analysis on iron status, and assessed associations of individual SNPs and quartiles of a multi-SNP score with NIMA. Quartile 4 versus quartile 1 of the multi-SNP score showed directionally consistent associations with the hypothesized direction of effect for all NIMA in women, indicating that increased body iron status is a risk factor for atherosclerosis in women. We observed no single SNP associations that fit the hypothesized directions of effect between iron and NIMA, except for rs651007, associated with decreased ferritin concentration and decreased atherosclerosis risk. Two of six NIMA-related SNPs showed association with the ratio hepcidin/ferritin, suggesting that an increased hepcidin/ferritin ratio increases atherosclerosis risk. Genomic correlations were close to zero, except for hepcidin and ferritin with ABI at rest [-0.27 (SE 0.34) and -0.22 (SE 0.35), respectively] and ABI after exercise [-0.29 (SE 0.34) and -0.30 (0.35), respectively]. The negative sign indicates an increased atherosclerosis risk with increased hepcidin and ferritin concentrations. CONCLUSIONS: Our results suggest a potential causal role for hepcidin and ferritin in atherosclerosis, and may indicate that iron status is causally related to atherosclerosis in women. PMID- 26159429 TI - Histopathological grading of breast ductal carcinoma in situ: validation of a web based survey through intra-observer reproducibility analysis. AB - BACKGROUND: Histopathological grading diagnosis of ductal carcinoma in situ (DCIS) of the breast may be very difficult even for experts, and it is important for therapeutic decisions. The challenge may be due to the inaccurate and/or subjective application of the diagnosis criteria. The aim of this study was to investigate the intra-observer agreement between a traditional method and a developed web-based questionnaire for scoring breast DCIS. METHODS: A cross sectional study was carried out to evaluate the diagnostic agreement of an electronic questionnaire and its point scoring system with the subjective reading of digital images for 3 different DCIS grading systems: Holland, Van Nuys and modified Black nuclear grade system. Three pathologists analyzed the same set of digitized images from 43 DCIS cases using two different web-based programs. In the first phase, they accessed a website with a newly created questionnaire and scoring system developed to allow the determination of the histological grade of the cases. After at least 6 months, the pathologists read again the same images, but without the help of the questionnaire, indicating subjectively the diagnoses. The intra-observer agreement analysis was employed to validate this innovative web-based survey. RESULTS: Overall, diagnostic reproducibility was similar for all histologic grading classification systems, with kappa values of 0.57 +/- 0.10, 0.67 +/- 0.09 and 0.67 +/- 0.09 for Holland, Van Nuys classification and modified Black nuclear grade system respectively. Only two 2-step diagnostic disagreements were found, one for Holland and another for Van Nuys. Both cases were superestimated by the web-based survey. CONCLUSION: The diagnostic agreement between the web-based questionnaire and a traditional method, both using digital images, is moderate to good for Holland, Van Nuys and modified Black nuclear grade system. The use of a scoring point system does not appear to pose a major risk of presenting large (2-step) diagnostic disagreements. These findings indicate that the use of this point scoring system in this web-based survey to grade objectively DCIS lesions is a useful diagnostic tool. PMID- 26159430 TI - Mohs micrographic surgery for periocular skin tumours in Ireland. AB - OBJECTIVE: To describe the shared care and outcomes of patients with periocular skin tumours who underwent Mohs micrographic surgery (MMS) performed by dermatologists, followed by oculoplastic reconstruction undertaken by ophthalmologists at two teaching and one private hospital in Ireland. RESEARCH DESIGN AND METHODS: This was a retrospective chart review at the Royal Victoria Eye and Ear Hospital, St James Hospital and the Hermitage Clinic. RESULTS: One hundred and twenty seven patients had periocular Mohs surgery between November 2006 and January 2013 mainly indicated for basal cell carcinoma. The mean follow up time was 2 years and to date there have been no local recurrences. CONCLUSIONS: MMS is available in Ireland and should be considered for patients with facial tumours in the ocular region. PMID- 26159431 TI - Procalcitonin: present and future. AB - Critically ill patients are frequently at risk of sepsis or inflammatory conditions. Procalcitonin (PCT) is a biomarker for critically ill patients to differentiate sepsis from non-infectious triggers of the systemic inflammatory response syndrome. It has been recently shown that PCT is a valuable tool to guide antibiotic treatment in patients with bacteria infections. However, PCT is also less than a universal and perfect biomarker, and its physiologic role remains unknown. An increase in PCT is associated not only with localized bacterial infection, but also with non-infectious disease or other microbial infections. Numerous studies have suggested that use of PCT would reduce patients' exposure to antibiotics; however, the use of PCT-guided management of antibiotics strategy needs further study to validate their safety in daily practice in ICU settings. Data supporting this concept from randomized trials are still required. Future studies should focus on PCT kinetics. On the other hand, the need for biologic role of PCT shall be highlighted. Immunoneutralization of PCT will likely be a therapeutic approach for human sepsis only if its physiologic effects are elaborated. The aim of this review is to summarize and discuss the current evidence for PCT in a series of clinical settings. PMID- 26159432 TI - Tonsillar colonisation of Fusobacterium necrophorum in patients subjected to tonsillectomy. AB - BACKGROUND: Fusobacterium necrophorum is a well-known cause of Lemirre's disease and accumulating evidence support its pathogenic role in peritonsillar abscess while its role in recurrent and chronic tonsillitis is uncertain. The objective of this study was to assess the prevalence of oropharyngeal colonisation with F. necrophorum and Beta-haemolytic streptococci in a cohort of patients scheduled for tonsillectomy due to recurrent or persistent throat pain, and to evaluate the dynamics of colonisation with repeated sampling during a follow-up time of 6 to 8 months. METHODS: Fifty-seven (57) patients aged 15-52 years scheduled for tonsillectomy due to chronic/recurrent tonsillitis or recurrent peritonsillar abscess were included. Throat swabs for the detection of F. necrophorum and Beta haemolytic streptococci and clinical data was collected at inclusion, at the time of surgery and 6 to 8 months after surgery. Statistical analysis was performed using the Chi-square, Fisher's exact and Mc Nemar tests. RESULTS: Fusobacterium necrophorum was found in 28, 30 and 16% of the patients at inclusion, surgery and follow up respectively. The corresponding results for beta-haemolytic streptococci were 5, 9 and 5%. Patients colonised with F. necrophorum at follow up, after tonsillectomy, were equally relieved from their previous throat pain as non-colonised patients. Looking at individual patients, the culture results for F. necrophorum varied over time, indicating a transient colonisation. CONCLUSION: Fusobacterium necrophorum was frequently found in throat cultures in this cohort of patients with recurrent or chronic throat pain leading to tonsillectomy. Colonisation was equally frequent in the asymptomatic cohort post-tonsillectomy, indicating that F. necrophorum is not alone causative of the symptoms. In an individual perspective, colonisation with F. necrophorum was transient over time. PMID- 26159433 TI - The electronic stethoscope. AB - Most heart diseases are associated with and reflected by the sounds that the heart produces. Heart auscultation, defined as listening to the heart sound, has been a very important method for the early diagnosis of cardiac dysfunction. Traditional auscultation requires substantial clinical experience and good listening skills. The emergence of the electronic stethoscope has paved the way for a new field of computer-aided auscultation. This article provides an in-depth study of (1) the electronic stethoscope technology, and (2) the methodology for diagnosis of cardiac disorders based on computer-aided auscultation. The paper is based on a comprehensive review of (1) literature articles, (2) market (state-of the-art) products, and (3) smartphone stethoscope apps. It covers in depth every key component of the computer-aided system with electronic stethoscope, from sensor design, front-end circuitry, denoising algorithm, heart sound segmentation, to the final machine learning techniques. Our intent is to provide an informative and illustrative presentation of the electronic stethoscope, which is valuable and beneficial to academics, researchers and engineers in the technical field, as well as to medical professionals to facilitate its use clinically. The paper provides the technological and medical basis for the development and commercialization of a real-time integrated heart sound detection, acquisition and quantification system. PMID- 26159434 TI - Water loss from litchi (Litchi chinensis) and longan (Dimocarpus longan) fruits is biphasic and controlled by a complex pericarpal transpiration barrier. AB - MAIN CONCLUSION: In litchi and longan fruits, a specialised pericarp controls water loss by a protective system consisting of two resistances in series and two water reservoirs separated by a barrier. In the fruits of litchi (Litchi chinensis) and longan (Dimocarpus longan), the pericarp is solely a protective structure lacking functional stomata and completely enclosing the aril that is the edible part. Maintaining a high water content of the fruits is crucial for ensuring the economic value of these important fruit crops. The water loss rates from mature fruits were determined and analysed in terms of the properties of the pericarps. Water loss kinetics and sorption isotherms were measured gravimetrically. The pericarps were studied with microscopy, and cuticular waxes and cutin were analysed with gas chromatography and mass spectrometry. The kinetics of fruit water loss are biphasic with a high initial rate and a lower equilibrium rate lasting for many hours. The outer and inner surfaces of the pericarps are covered with cuticles. Litchi and longan fruits have a unique type of transpiration barrier consisting of two resistances in series (endo- and exocarp cuticles) and two reservoirs of water (aril and mesocarp). The exocarp permeability controls the water loss from fresh fruits while in fruits kept for an extended time at low relative humidity it is determined by the endo- and exocarp permeabilities. Permeances measured are within the range for typical fruit cuticles. The findings may be used to design optimal postharvest storage strategies for litchi and longan fruits. PMID- 26159435 TI - Ecological turmoil in evolutionary dynamics of plant-insect interactions: defense to offence. AB - MAIN CONCLUSION: Available history manifests contemporary diversity that exists in plant-insect interactions. A radical thinking is necessary for developing strategies that can co-opt natural insect-plant mutualism, ecology and environmental safety for crop protection since current agricultural practices can reduce species richness and evenness. The global environmental changes, such as increased temperature, CO2 and ozone levels, biological invasions, land-use change and habitat fragmentation together play a significant role in re-shaping the plant-insect multi-trophic interactions. Diverse natural products need to be studied and explored for their biological functions as insect pest control agents. In order to assure the success of an integrated pest management strategy, human activities need to be harmonized to minimize the global climate changes. Plant-insect interaction is one of the most primitive and co-evolved associations, often influenced by surrounding changes. In this review, we account the persistence and evolution of plant-insect interactions, with particular focus on the effect of climate change and human interference on these interactions. Plants and insects have been maintaining their existence through a mutual service resource relationship while defending themselves. We provide a comprehensive catalog of various defense strategies employed by the plants and/or insects. Furthermore, several important factors such as accelerated diversification, imbalance in the mutualism, and chemical arms race between plants and insects as indirect consequences of human practices are highlighted. Inappropriate implementation of several modern agricultural practices has resulted in (i) endangered mutualisms, (ii) pest status and resistance in insects and (iii) ecological instability. Moreover, altered environmental conditions eventually triggered the resetting of plant-insect interactions. Hence, multitrophic approaches that can harmonize human activities and minimize their interference in native plant-insect interactions are needed to maintain natural balance between the existence of plants and insects. PMID- 26159436 TI - Ultrasound guidance versus direct palpation for radial artery catheterization by expert operators: a randomized trial among Canadian cardiac anesthesiologists. AB - PURPOSE: The use of ultrasound (US) for radial arterial catheterization has been reported to result in faster insertion times with fewer complications when compared with traditional direct palpation (DP). We sought to determine if this applies to expert operators and tested the hypothesis that, among cardiac anesthesiologists, US-guided insertion similarly results in faster insertion times as well as fewer re-directs, attempts, and complications. METHODS: Following Research Ethics Board Approval, we conducted a randomized clinical trial in 125 patients scheduled for cardiac surgery at a single tertiary/quaternary care centre. Patients were randomized to either US- or DP guided radial artery catheterization by attending cardiac anesthesiologists. The primary endpoint was time to catheter placement. Secondary endpoints included the number of attempts and re-directs as well as the failure rate. RESULTS: There were no differences between the DP- (n = 62) vs US-guided (n = 63) groups in median [interquartile range] time to placement (104 [76-212] sec vs 104 [68-270] sec, respectively; P = 0.66), number of re-directs (2 [0-6] vs 3 [1-5], respectively; P = 0.82), or number of attempts (1 [1-2] vs 1 [1-2], respectively; P = 0.08). The first-attempt success rate was 56.4% in the DP group and 71.4 % in the US group (P = 0.10). Failure rate and hematoma rate in the DP group were 21.0% and 22.6%, respectively, compared with 12.7% and 11.1% in the US group (P = 0.24 and 0.10, respectively). CONCLUSIONS: Among experienced cardiac anesthesiologists, the use of US to facilitate radial arterial catheterization did not affect insertion times, the number of re-directs, or the number of attempts when compared with DP. Ultrasound use had no significant effects on the rates of success on first attempt, failure, or hematoma formation. This trial was registered at www.clinicaltrials.gov : NCT02118441. PMID- 26159437 TI - Involvement of NO-cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia. AB - The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20 mg/kg, per os (p.o.) or L-NAME 20 mg/kg, intraperitoneally (i.p.) and TAD (20 mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55 +/- 2 degrees C. In carrageenan- and diabetes induced hyperalgesia, TAD (10 and 20 mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20 mg/kg) with TAD (20 mg/kg) showed significant difference in PWLs as compared to the TAD (20 mg/kg), indicating L NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect. PMID- 26159438 TI - Diagnosis and management of Transposition of great arteries within a pediatric cardiology network with the aid of telemedicine: A case report from Brazil. AB - We present a case of a newborn from a remote, underserved area in the inland of Paraiba, a state from Northeast Brazil. She presented with clinical cyanosis at birth. With the aid of telemedicine, a neonatologist under online cardiology supervision performed a screening echocardiogram. The session established the diagnosis of simple transposition of the great vessels in the baby's first few hours of life. During the same telemedicine session, the necessary arrangements for transferal to a larger maternity center took place. The baby was maintained stable on prostaglandins and was subsequently transferred to a tertiary cardiac center in the neighboring State, Pernambuco. She underwent anatomical correction at day 10, presented no surgical or postoperative complications, and was discharged home at the age of 21 days. She is now over three years old and continues her follow-up care mostly at her hometown, with local pediatricians under online supervision by a cardiologist in a virtual outpatient clinic. The establishment of a Pediatric Cardiology Network, with the aid of telemedicine, can produce a major impact on the access to specialized health care for poor regions of developing countries. PMID- 26159439 TI - Images in vascular medicine. Severe vasovagal event following attempted intubation in a patient with bilateral retropharyngeal carotid arteries. PMID- 26159440 TI - Photoacoustic image patterns of breast carcinoma and comparisons with Magnetic Resonance Imaging and vascular stained histopathology. AB - Photoacoustic (optoacoustic) imaging can visualize vasculature deep in tissue using the high contrast of hemoglobin to light, with the high-resolution possible with ultrasound detection. Since angiogenesis, one of the hallmarks of cancer, leads to increased vascularity, photoacoustics holds promise in imaging breast cancer as shown in proof-of-principle studies. Here for the first time, we investigate if there are specific photoacoustic appearances of breast malignancies which can be related to the tumor vascularity, using an upgraded research imaging system, the Twente Photoacoustic Mammoscope. In addition to comparisons with x-ray and ultrasound images, in subsets of cases the photoacoustic images were compared with MR images, and with vascular staining in histopathology. We were able to identify lesions in suspect breasts at the expected locations in 28 of 29 cases. We discovered generally three types of photoacoustic appearances reminiscent of contrast enhancement types reported in MR imaging of breast malignancies, and first insights were gained into the relationship with tumor vascularity. PMID- 26159441 TI - The Severity of Liver Fibrosis Influences the Prognostic Value of Inflammation Based Scores in Hepatitis B-Associated Hepatocellular Carcinoma. AB - BACKGROUND: This study was designed to evaluate the prognostic value of three systemic inflammation markers, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), for hepatocellular carcinoma (HCC) associated with hepatitis B (HBV). METHODS: This analysis included 234 HBV-HCC patients who underwent primary surgical resection at the Mount Sinai Medical Center between 1988 and 2013. Serum albumin and circulating neutrophil, lymphocyte, and platelet counts immediately before surgery were obtained to calculate NLR, PLR, and PNI. RESULTS: Patients with larger tumor size (>3 cm) had higher NLR, higher PLR, and lower PNI. Stratified analysis showed that the impact of three markers on outcome depends on the severity of liver fibrosis. High NLR, high PLR, or low PNI was associated with poor outcome only in patients without end-stage fibrosis (Ishak stage 0-5) and not in those with cirrhosis (Ishak stage 6). Multivariate analysis in Ishak stage 0-5 patients showed that only high NLR was associated with poor outcome independent of tumor size. Of the three markers, only NLR correlated with PD-L1 expression in center of tumor, but not in nonneoplastic liver. CONCLUSIONS: The prognostic value of these three markers following surgery was only significant for HBV-HCC patients without end-stage fibrosis, and among the three markers, only NLR remained a significant prognostic indicator independent of tumor size. The correlation of NLR with intratumoral PD-L1 expression raises a hypothesis for shared pathways leading to PD-L1-mediated local tolerance within tumor and systemic inflammatory responses represented by elevated NLR in HBV-HCC. PMID- 26159442 TI - Clinicopathologic Features and Outcomes of Non-B, Non-C Hepatocellular Carcinoma After Hepatectomy. AB - PURPOSE: This retrospective study aimed to investigate the clinical characteristics and long-term outcomes after hepatectomy in patients with non-B, non-C (NBNC) hepatocellular carcinoma (HCC) who were negative for hepatitis B virus surface antigen and anti-hepatitis C virus antibody. METHODS: We retrospectively reviewed 666 patients with HCC who underwent hepatectomy. The patients were divided into NBNC-HCC patients [n = 117 (17.6 %)] and hepatitis virus (HV)-HCC patients [n = 547 (82.4 %)]. We compared the clinicopathologic characteristics and long-term outcomes between the 2 groups. Two patients with incomplete virus-marker data were not analyzed. RESULTS: NBNC-HCC patients had better liver function but more advanced and larger HCCs and a high incidence of intrahepatic metastasis compared to HV-HCC patients. Recurrence-free and overall survival were similar in both groups. Multivariate analysis showed that aspartate aminotransferase (AST) and alpha-fetoprotein were independently associated with disease-free and overall survival in NBNC-HCC patients after hepatectomy. High AST was significantly associated with tumor size and rate of capsule formation with cancer cell infiltration in NBNC-HCC patients, but not with other liver function tests, fibrosis, or necrosis of noncancerous lesions. CONCLUSIONS: NBNC HCC patients have better liver function than HV-HCC patients, despite having more advanced HCC at diagnosis. There were no differences in long-term outcomes after hepatectomy between NBNC-HCC and HV-HCC patients. Preoperative AST and alpha fetoprotein were independently associated with the prognosis of NBNC-HCC after hepatectomy. Serum AST levels might be associated with tumor malignancy in NBNC HCC patients. PMID- 26159444 TI - Advances in pharmacotherapy to treat kidney transplant rejection. AB - INTRODUCTION: Current immunosuppressive combination therapy provides excellent prevention of T-cell-mediated rejection following renal transplantation; however, antibody-mediated rejection remains of high concern and accounts for a large number of long-term allograft losses. The recent development of protocol biopsies resulted in the definition of subclinical rejection (SCR), showing histologic evidence for rejection but unremarkable clinical course. AREAS COVERED: This review describes the current knowledge and evidence of pharmacotherapy to treat kidney allograft rejections and covers SCR treatment options. Each substance is analyzed with regard to its classical indication and further discussed for the treatment of other forms of rejection. EXPERT OPINION: Despite a lack of randomized trials, early acute T-cell-mediated rejection can be treated effectively in most cases without graft loss. The necessity to treat SCR is currently unclear. Due to a lack of effective therapies, new treatment approaches for antibody-mediated rejection are an urgent medical need to improve long-term outcomes. Future research should aim to better define pathophysiology and histology, stratify risk, and develop rational treatment strategies from randomized controlled trials, in order to establish the value of novel therapies in the arsenal of rejection pharmacotherapy. However, the effective prevention of rejection with minimal side effects still remains the goal in immunosuppression. PMID- 26159443 TI - Dietary and Behavioral Adjustments to Manage Bowel Dysfunction After Surgery in Long-Term Colorectal Cancer Survivors. AB - BACKGROUND: Bowel dysfunction is a known complication of colorectal cancer (CRC) surgery. Poor bowel control has a detrimental impact on survivors' health-related quality of life (HRQOL). This analysis describes the dietary and behavioral adjustments used by CRC survivors to manage bowel dysfunction and compares adjustments used by survivors with permanent ostomy to those with anastomosis. METHODS: This mixed-methods analysis included pooled data from several studies that assessed HRQOL in CRC survivors. In all studies, CRC survivors with or without permanent ostomies (N = 856) were surveyed using the City of Hope Quality of Life Colorectal Cancer tool. Dietary adjustments were compared by ostomy status and by overall HRQOL score (high vs. low). Qualitative data from 13 focus groups and 30 interviews were analyzed to explore specific strategies used by survivors to manage bowel dysfunction. RESULTS: CRC survivors made substantial, permanent dietary, and behavioral adjustments after surgery, regardless of ostomy status. Survivors who took longer after surgery to become comfortable with their diet or regain their appetite were more likely to report worse HRQOL. Adjustments to control bowel function were divided into four major strategies: dietary adjustments, behavioral adjustments, exercise, and medication use. CONCLUSIONS: CRC survivors struggled with unpredictable bowel function and may fail to find a set of management strategies to achieve regularity. Understanding the myriad adjustments used by CRC survivors may lead to evidence-based interventions to foster positive adjustments after surgery and through long-term survivorship. PMID- 26159445 TI - Advancements in the treatment of agitation in Alzheimer's disease. AB - INTRODUCTION: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks well-established long-term interventions that are both effective and safe. While non-pharmacological interventions are the suggested first-line treatment, it isn't effective in managing symptoms for every patient. In such cases, clinicians turn to the use of pharmacological interventions. Traditionally, these interventions consist of off label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine and antidepressants, where the efficacy doesn't necessarily outweigh the associated risks. AREAS COVERED: Gains made in understanding the neurobiological mechanisms underlying agitation have fueled several recent clinical trials. A comprehensive literature search for published articles evaluating pharmacologic interventions for agitation in AD was done. A review of some of these clinical trials was completed: dextromethorphan/quinidine, scyllo-inositol, brexpiprazole, prazosin, cannabinoids, dronabinol and citalopram show promise in treating agitation. EXPERT OPINION: Neurobiological findings and enhanced trial designs have re ignited the area of pharmacological treatment of NPS. Although further research is needed to fully determine the safety, tolerability and efficacy of these treatments, the mission to finding effective treatments for NPS such as agitation in patients with dementia is well underway. PMID- 26159446 TI - Pharmacological treatment for generalized anxiety disorder in adults: an update. AB - INTRODUCTION: Modest response and remission rates for the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, coupled with mounting evidence that the tolerability of the antidepressants (ADs) may have been overstated in the literature, has contributed to changes in prescribing patterns for generalized anxiety disorder (GAD). New interest in the absence of evidence that supports these standard therapies as superior to benzodiazepines stimulated a review of the literature. AREAS COVERED: A literature search was conducted in the MedLine database with search terms 'generalized anxiety disorder' and 'treatment' for purposes of including relevant literature related to pharmacologic treatment of GAD. Aside from a review of pivotal literature, the authors also included newer studies that evaluated novel drug treatments. Last, the database was searched for benzodiazepine comparisons to standard therapy secondary to concerns that such literature is sparse. The review of newer modalities and the decision to include related literature was also based on the strength of the evidence and the status of their approval for the treatment of GAD. EXPERT OPINION: Although ADs remain the most frequently prescribed medications for GAD, alternative and off-label therapies such as pregabalin, the atypical antipsychotics and vortioxetine are garnering interest. Based on the evidence available to us, it is our recommendation that along with the ADs, benzodiazepines be considered a possible first-line therapy in eligible patients based on the discretion and clinical judgment of the treating physician. PMID- 26159447 TI - Advances in pharmacotherapy for secondary hyperparathyroidism. AB - INTRODUCTION: Secondary hyperparathyroidism is a frequent complication of chronic kidney disease. This review will discuss the various therapeutic options available for the management of hyperparathyroidism. AREAS COVERED: The main therapeutic strategies available to prevent or slow down the progression of hyperparathyroidism will be detailed here. Reductions in phosphatemia may be achieved by controlling dietary phosphorus, administering phosphorus binders, or increasing the frequency of dialysis sessions. Vitamin D sterols reduce parathyroid hormone (PTH) secretion while normalizing calcium (Ca) and vitamin D levels. Calcimimetics decrease PTH levels, probably with an additional effect on hyperplasia. Percutaneous injections in parathyroids represent an option useful in cases of hyperparathyroidism resistant to pharmacological therapy. Pubmed was searched by combining the terms 'secondary hyperparathyroidism' and the name of each one of the drugs reported in this review. EXPERT OPINION: PTH increases from early stages of renal disease. One of the goals in pre-dialysis is the prevention of hyperphosphatemia and the maintenance of Ca levels in the normal range. The management of hyperparathyroidism in dialysis requires control of phosphorus level. In this stage, the decision to use calcimimetics and vitamin D derivatives should be made according to serum levels of Ca and phosphorus. PMID- 26159448 TI - Sodium zirconium cyclosilicate (ZS-9) for the treatment of hyperkalemia. AB - INTRODUCTION: Hyperkalemia is a common, sometimes fatal electrolyte abnormality seen in patients with heart failure (HF) or kidney disease. Acute treatments that cause the intracellular translocation of potassium can be effective in the short term but they simply buy time until definitive removal by dialysis or binding agents (e.g., sodium polystyrene sulfonate) can occur. In contrast, treatment for chronic hyperkalemia, which often occurs in the setting of HF treated with renin angiotensin-aldosterone inhibitors (RAASi) or mineralocorticoid receptor antagonists (MRA), is limited and has questionable efficacy. AREAS COVERED: Sodium zirconium cyclosilicate (ZS-9), a novel, non-absorbed, potassium-selective cation exchanger, has demonstrated activity in acutely lowering and maintaining normal potassium levels. When used chronically, maintenance of normal serum potassium has been demonstrated for up to 1 month. Although higher doses of ZS-9 have been associated with modest increases in the rates of edema and hypokalemia, the overall adverse event rate is similar to placebo. EXPERT OPINION: The efficacy of ZS9 has been shown in patients with chronic hyperkalemia, offering promise for conditions such as HF, where optimized therapy with RAASi and MRA is often limited by a concomitant, drug-induced increase in potassium. Further, in acute hyperkalemia it has potential to become an important option by rapidly lowering potassium levels, thus delaying or potentially averting the need for emergent dialysis. While further randomized trials demonstrating improved clinical outcomes are required for both these indications, initial data suggests a promising role for this agent in the management of both acute and chronic hyperkalemia. PMID- 26159450 TI - [Diagnostic value of left bundle branch block in patients with acute myocardial infarction. A prospective analysis]. AB - BACKGROUND: In contemporary practice with early catheterization in most patients with suspected acute myocardial infarction, the clinical utility of new or presumably new left bundle branch block (LBBB) as a diagnostic criterion equivalent to ST-segment elevation is not well established. This study therefore aimed to determine the predictive value of LBBB for the diagnosis of acute transmural myocardial infarction (or ST-segment elevation myocardial infarction, STEMI). PATIENTS AND METHODS: Between November 2006 and December 2011, 1,139 consecutive patients presenting to the heart center of the University of Cologne with suspected STEMI were examined. Of these patients, 935 presented with ST elevation, 72 with LBBB, and 132 had neither of these ECG changes. The diagnosis was confirmed with immediate coronary angiography. RESULTS: Compared with ST segment elevation, LBBB was associated with a higher prevalence of cardiovascular risk factors and end-organ damage, and more patients with LBBB presented with pulmonary edema or cardiogenic shock (Killip III/IV). STEMI was confirmed in 58.3 % of patients with LBBB and in 86.4 % with ST-segment elevation. The sensitivity (0.38 [0.29-0.46]; odds ratio: 1.24) and specificity (0.67 [0.58-0.77]) of LBBB for the prediction of STEMI were low. However, the additional assessment of troponin T (> 0.1 ug/l) increased the predictive value of LBBB significantly. After adjusting for age and gender, no difference in mortality was found between the groups. CONCLUSION: LBBB with acute chest pain characterizes a cohort of patients with high morbidity and mortality. For the triage of these patients at first contact, additional criteria should be evaluated, which could increase the specificity of LBBB for the diagnosis of STEMI. PMID- 26159451 TI - Is researching adverse events in hospital deaths a good way to describe patient safety in hospitals: a retrospective patient record review study. AB - OBJECTIVE: Adverse event studies often use patient record review as a way to assess patient safety. As this is a time-consuming method, hospitals often study inpatient deaths. In this article we will assess whether this offers a representative view of the occurrence of adverse events in comparison to patients who are discharged while still living. DESIGN: Retrospective patient record review study. SETTING AND PARTICIPANTS: A total of 11,949 hospital admissions; 50% of inpatient deaths; the other half of patients discharged while alive. The data originated from our two national adverse event studies in 2004 and 2008. MAIN OUTCOME MEASURES: Overall adverse events and preventable adverse events in inpatient deaths, and in admissions of patients discharged alive. We looked at size, preventability, clinical process and type of adverse events. RESULTS: Patients who died in hospital were on an average older, had a longer length of stay, were more often urgently admitted and were less often admitted to a surgical unit. We found twice as many adverse events and preventable adverse events in inpatient deaths than in patients discharged alive. Consistent with the differences in patient characteristics, preventable adverse events in inpatient deaths were proportionally less and were often related to the surgical process. Most types of adverse events and preventable adverse events occur in inpatient deaths as well as in patients discharged alive; however, these occur more often in inpatient deaths and are differently distributed. CONCLUSIONS: Reviewing patient records of inpatient deaths is more efficient in identifying preventable AEs than reviewing records of those discharged alive. Although many of the same types of adverse events are found, it does not offer a representative view of the number or type of adverse events. PMID- 26159452 TI - To tweet or not to tweet about schizophrenia systematic reviews (TweetSz): study protocol for a randomised controlled trial. AB - INTRODUCTION: The Cochrane Schizophrenia Group (CSzG) has produced and maintained systematic reviews of effects of interventions for schizophrenia and related illness. Each review has a Plain Language Summary (PLS), for those without specialised knowledge, and an abstract, which are freely available from The Cochrane Library (https://summaries.cochrane.org). Increasingly, evidence is being distributed using social media such as Twitter and Weibo (in China) alongside traditional publications. METHODS AND ANALYSIS: In a prospective two arm, parallel, open randomised controlled trial with a 1:1 allocation ratio, we will allocate 170 published systematic reviews into the intervention group (tweeting arm/Weibo arm) versus the control group (non-tweeting arm). Reviews will be stratified by baseline access activity, defined as high (>=19 views per week, n=14), medium (4.3 to 18.99 views per week, n=72) or low (<4.3 views per week, n=84), based on Google Analytics, which will also be used for evaluating outcomes. The intervention group will have three tweets daily using Hootsuite with a slightly different accompanying text (written by CEA and AB) and a shortened Uniform Resource Locator (URL) to the PLS: a) The review title as it appears in summaries.cochrane.org, b) A pertinent extract from results or discussion sections of the abstract and c) An intriguing question or pithy statement related to the evidence in the abstract. The primary outcome will be: total number of visits to a PLS in 7 days following the tweet. Secondary outcomes will include % new visits, bounce rate, pages per visit, visit duration, page views, unique page views, time on page, entrances, exiting behaviour and country distribution. ETHICS AND DISSEMINATION: This study does not involve living participants, and uses information available in the public domain. Participants are published systematic reviews, hence, no ethical approval is required. Dissemination will be via Twitter, Weibo and traditional academic means. TRIAL REGISTRATION NUMBER: ISRCTN84658943. PMID- 26159453 TI - Visual acuity and contrast sensitivity following Descemet stripping automated endothelial keratoplasty. AB - PURPOSE: To describe improvements in visual acuity and contrast sensitivity following Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: We analysed 128 consecutive patients (128 eyes) with Fuchs endothelial dystrophy (FED) and bullous keratopathy (BK) who underwent DSAEK at a single tertiary referral centre from January 2006 to September 2009. Our main outcome measures were best-corrected visual acuity (BCVA) and contrast sensitivity over 24 months follow-up. RESULTS: Median age was 67 (60-73) years with 55% women (n=70) and majority Chinese (74%, n=94) in our Asian population. There were no significant differences between demographics between the FED (48%, 61 eyes) and BK (52%, 67 eyes) groups. Forward multivariate linear regression adjusted for age, gender, donor graft thickness and diagnosis (FED vs BK) revealed that preoperative visual acuity was the most significant factor associated with visual acuity at 1 year (B=0.032, p=0.03, R(2)=0.122). Visual recovery was longer in eyes with BK, with a significantly better visual acuity in the FED group at 12 months (mean logarithm of the minimum angle of resolution BCVA BK: 0.27+/-0.1 vs FED: 0.22+/-0.9; p=0.001), but not significant at 24 months (p=0.154). Contrast sensitivity significantly improved more in the first 6 months in the FED when compared with the BK group (at 3.0, 6.0 and 12.0 cycles per degree, p<0.01). CONCLUSIONS: Our study suggests that while there was significant improvement in contrast sensitivity and visual acuity after DSAEK, poor preoperative visual acuity was associated with an inferior visual outcome and the time to recovery was longer in eyes with BK. PMID- 26159454 TI - Changing trends over the last decade in the aetiology of childhood blindness: a study from a tertiary referral centre. AB - AIMS: To discern treatable and preventable causes of childhood blindness by evaluating the aetiologic factors, and to compare the distribution of the most commonly affected anatomic sites of severe visual impairment (SVI) with our previous published data. METHODS: The charts of 11 871 patients followed between June 2002 and May 2014 were reviewed retrospectively, and 695 patients (5.9%) who had SVI or blindness in accordance with WHO criteria were enrolled. The results of ophthalmologic examinations and coexistence of any systemic disease were documented and checked against our published clinic data concerning the aetiology of childhood blindness before 2002. chi(2) test was used for statistics. RESULTS: Mean age was 47.0+/-51.9 months (median: 24 months). Cortical visual impairment (CVI) was present in 212 cases (30.5%) and 20.3% of those had a history of premature birth. The most common anatomic sites of SVI were retina (24.6%) and crystalline lens (17.1%). When compared with our previous data, we found a significant increase in the prevalence of CVI (p=0.046) and decrease in the frequency of SVI due to uveal disorders (p<0.001). Prevalence of blindness secondary to retinopathy of prematurity reduced by a third (p=0.280), and a significant decrease in aphakia-related SVI (p=0.028) was achieved within the last decade. CONCLUSIONS: The prevalence of CVI was found to be relatively increased due to the significant reduction in the frequency of preventable causes of SVI. Furthermore our clinical practice for visual rehabilitation in aphakia has resulted in a considerable decrease in SVI in the last decade. PMID- 26159455 TI - Pridopidine selectively occupies sigma-1 rather than dopamine D2 receptors at behaviorally active doses. AB - RATIONALE: Dopamine stabilizers have stimulatory actions under low dopamine tone and inhibitory actions under high dopamine tone without eliciting catalepsy. These compounds are dopamine D2 receptor (D2R) antagonists or weak partial agonists and may have pro-mnemonic and neuroprotective effects. The mechanism underlying their stimulatory and neuroprotective actions is unknown but could involve sigma-1R binding. OBJECTIVES: The present study examined sigma-1R and D2R occupancy by the dopamine stabilizer pridopidine (ACR16) at behaviorally relevant doses in living rats. METHODS: Rats were administered 3 or 15 mg/kg pridopidine, or saline, before injection of the radiotracer (11)C-SA4503 (sigma-1R) or (11)C raclopride (D2R). Some animals received 60 mg/kg pridopidine and were only scanned with (11)C-raclopride. Cerebral (11)C-SA4503 binding was quantified using metabolite-corrected plasma input data and distribution volume (V T) calculated by Logan graphical analysis. (11)C-raclopride binding was quantified using striatum-to-cerebellum ratios and binding potentials calculated with a simplified reference tissue model. RESULTS: Cunningham-Lassen plots indicated sigma-1R occupancies of 57 +/- 2 and 85 +/- 2% after pretreatment of animals with 3 and 15 mg/kg pridopidine. A significant (44-66%) reduction of (11)C-raclopride binding was only observed at 60 mg/kg pridopidine. CONCLUSIONS: At doses shown to elicit neurochemical and behavioral effects, pridopidine occupied a large fraction of sigma-1Rs and a negligible fraction of D2Rs. Significant D2R occupancy was only observed at a dose 20-fold higher than was required for sigma-1R occupancy. The characteristics of dopamine stabilizers may result from the combination of high sigma-1R and low D2R affinity. PMID- 26159456 TI - Prevention of the incubation of cocaine seeking by aerobic exercise in female rats. AB - BACKGROUND: Recent research has demonstrated that aerobic exercise can attenuate craving for drugs of abuse and reduce escalation and reinstatement of drug seeking behavior in animal models. The present study examined the effects of aerobic exercise on the development of the incubation of cocaine-seeking behavior or the progressive increase in cocaine seeking over a protracted withdrawal period from cocaine self-administration. METHODS: Female rats were trained to self-administer cocaine (0.4 mg/kg/inf) during daily 6-h sessions for 10 days. Subsequently, access to cocaine and cocaine-paired cues was discontinued during a 3- or 30-day withdrawal period when rats had access to either a locked or unlocked running wheel. At the end of the withdrawal period, rats were reintroduced to the operant conditioning chamber and reexposed to cocaine-paired cues to examine cocaine-seeking behavior under extinction conditions. RESULTS: Rats with access to a locked running wheel during 30 days of withdrawal had significantly greater cue-induced cocaine-seeking behavior than rats that had access to an unlocked running wheel for 30 days. Further, there was robust incubation of cocaine seeking in rats with access to a locked running wheel as cocaine seeking was notably elevated at 30 vs. 3 days of withdrawal. However, cocaine-seeking behavior did not differ between rats with access to an unlocked running wheel for 30 vs. 3 days, indicating that incubation of cocaine seeking was suppressed following access to exercise for 30 days. CONCLUSION: Aerobic exercise during extended withdrawal from cocaine self-administration decreased incubation of cue-induced cocaine-seeking behavior and may reduce vulnerability to relapse. PMID- 26159458 TI - BCR-ABL1 Transcript Levels at 3 and 6 Months Are Better for Identifying Chronic Myeloid Leukemia Patients with Poor Outcome in Response to Second-Line Second Generation Tyrosine Kinase Inhibitors after Imatinib Failure: A Report from a Single Institution. AB - Early reduction of BCR-ABL1 transcript levels has been associated with improved outcome in chronic myeloid leukemia (CML) treatment. We evaluated 54 chronic phase CML patients treated with imatinib who switched therapy to dasatinib (n = 33) or nilotinib (n = 21). BCR-ABL1 transcript levels were measured in peripheral blood using real-time quantitative PCR (RQ-PCR) every 3 months from the start of second-line treatment. Patients with BCR-ABL transcript levels >10% at 3 months and >1% at 6 months had significantly inferior progression-free (PFS) and event free survival (EFS) than patients with RQ-PCR <10% at 3 months and <1% at 6 months (66 vs. 100%, p = 0.01, and 33 vs. 73%, p = 0.02, respectively). Patients with RQ-PCR <10% at 3 months and >1% at 6 months also had inferior PFS and EFS than patients with RQ-PCR <10% at 3 months and <1% at 6 months (48 vs. 100%, p = 0.002, and 25 vs. 73%, p < 0.0001, respectively). Two measurements of BCR-ABL levels were better than a single one to stratify chronic-phase CML patients as failure after second-line therapy. PMID- 26159457 TI - Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice. AB - Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4 weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity. PMID- 26159459 TI - Myospherulosis of the Mandible Presenting as a Multilocular Lesion: A Case Report and Review of the Literature. AB - Myospherulosis is an uncommon foreign body reaction that occurs in tissues exposed to antibiotic and oil-based ointments. Radiographic imaging of this lesion may suggest other diagnoses. Treatment consists of conservative surgical removal, and is usually curative. We report herein a case of myospherulosis presenting as an extremely unusual multilocular radiolucent lesion. PMID- 26159460 TI - MiR-378 Plays an Important Role in the Differentiation of Bovine Preadipocytes. AB - BACKGROUND: Adipocyte, the main cellular component of white adipose tissue, plays a vital role in energy balance in higher eukaryotes. In recent years, adipocytes have also been identified as a major endocrine organ involved in immunological responses, vascular diseases, and appetite regulation. In farm animals, fat content and categories are closely correlated with meat quality. MicroRNAs (miRNAs), a class of endogenous single-stranded non-coding RNA molecules, participate in the regulation of adipocyte differentiation and adipogenesis through regulating the transcription or translation of target mRNAs. MiR-378 plays an important role in a number of biological processes, including cell growth, cell differentiation, tumor cell survival and angiogenesis. METHODS: In the present study, bioinformatics analysis and dual-luciferase reporter assay were used to identify and validate the target genes of miR-378. In vitro cell transfection, quantitative reverse transcription polymerase chain reaction (RT qPCR), western blot analysis, Oil Red O staining, and triglyceride content measurement were conducted to analyze the effects of miR-378 on bovine preadipocyte differentiation. RESULTS: MiR-378 was induced during adipocyte differentiation. In the differentiated adipocytes overexpressing miR- 378, the volume of lipid droplets was enlarged, and the triglyceride content was increased. Moreover, the mRNA expression levels of the adipocyte differentiation marker genes, peroxisome proliferator-activated receptor gamma (PPARgamma) and sterol regulatory element-binding protein (SREBP), were significantly elevated in the differentiated, mature adipocytes. In contrast, the mRNA expression level of preadipocyte factor 1 (Pref-1) was markedly reduced. E2F transcription factor 2 (E2F2) and Ras-related nuclear (RAN)-binding protein 10 (RANBP10) were the two target genes of miR-378. The mRNA expression levels of E2F2 and RANBP10 did not significantly change in bovine preadipocytes overexpressing miR-378. However, the protein expression levels of E2F2 and RANBP10 were markedly reduced. CONCLUSION: MiR-378 promoted the differentiation of bovine preadipocytes. E2F2 and RANBP10 were the two target genes of miR-378, and might involve in the effects of miR-378 on the bovine preadipocyte differentiation. PMID- 26159461 TI - Persisting Effects of Concussion on Heart Rate Variability during Physical Exertion. AB - The purpose of this study was to evaluate cardiac autonomic modulation in university athletes during the post-acute to late phase (mean, 95 days +/-63) of injury at rest and during physical exertion. We also sought to evaluate the effect of time since injury and number of injuries on heart rate variability (HRV). We hypothesized that physical exertion would reveal persisting modifications in HRV following a concussion. We included, in a cross-sectional design, athletes who sustained a concussion and matched controls. Concussions were identified by a medical doctor using established criteria. Twelve male concussed and 12 control athletes took part in the study. Control participants were teammates who were chosen to match the concussed athletes with regard to their height, weight, education, and age. The beat-to-beat electrocardiogram intervals of the participants were measured at rest and during physical exertion (isometric hand grip contraction; IHGC), which was sustained for 3 minutes at 30% of the participants' maximum. Linear and nonlinear parameters of HRV were calculated. The ratio between low and high frequency (LF/HF) bands was calculated to assess the sympathovagal balance. During the IHGC, but not at rest, concussed athletes presented significantly lower power in HF bands, leading to a significantly higher LF/HF ratio (p <= 0.05). Thus, asymptomatic athletes still may exhibit modifications in cardiac autonomic modulation weeks to months following injury. These modifications may only become apparent during physical exertion. Monitoring HRV may aid diagnosis and provide insight about safe return to play. PMID- 26159463 TI - Scrutinizing the role of size reduction on the exchange bias and dynamic magnetic behavior in NiO nanoparticles. AB - NiO nanoparticles (NPs) with a nominal size range of 2-10 nm, synthesized via high-temperature pyrolysis of a nickel nitrate, have been extensively investigated using neutron diffraction and magnetic (ac and dc) measurements. The magnetic behavior of the NPs changes noticeably when their diameter decreases below 4 nm. For NPs larger than or equal to this size, Rietveld analysis of the room temperature neutron diffraction patterns reveals that there is a reduction in the expected magnetic moment per [Formula: see text] ion with respect to bulk NiO, which is linked to the existence of a magnetically disordered shell at the NP surface. The presence of two peaks in the temperature dependence of both the dc magnetization after zero-field-cooling and the real part of the ac magnetic susceptibility is explained in terms of a core (antiferromagnetic, AFM)/shell (spin glass, SG) morphology. The high-temperature peak ([Formula: see text] K) is associated with collective blocking of the uncompensated magnetic moments inside the AFM core. The low-temperature peak ([Formula: see text] K) is a signature of a SG-like freezing of the surface [Formula: see text] spins. In addition, an exchange bias (EB) effect emerges due to the core/shell magnetic coupling. The cooling field and temperature dependences of the EB effect and the coercive field are discussed in terms of the core size and the effective magnetic anisotropy of the NPs. However, NiO NPs of 2 nm in size no longer show AFM order and the [Formula: see text] magnetic moments freeze into a SG-like state below [Formula: see text] K, with no evidence of EB effect. PMID- 26159462 TI - Regulation of Cardiac Autonomic Nervous System Control across Frailty Statuses: A Systematic Review. AB - BACKGROUND: Frailty is a geriatric syndrome that leads to impairment in interrelated physiological systems and progressive homeostatic dysregulation in physiological systems. OBJECTIVE: The focus of the present systematic review was to study the association between the activity of the cardiac autonomic nervous system (ANS) and frailty. METHODS: A systematic literature search was conducted in multiple databases: PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov; the last search was performed in March 2015. Inclusion criteria were: (1) that the studied population was classified for frailty according to a standard definition, such as Fried's criteria; (2) that the study had a nonfrail control group, and (3) that heart rate (HR) and/or heart rate variability (HRV) were parameters of interest in the study. RESULTS: Of the 1,544 articles screened, 54 were selected for full-text review and 6 studies met the inclusion criteria. Assessment of HRV using different standard time domain, frequency domain, and nonlinear domain approaches confirmed the presence of an impaired cardiac ANS function in frail compared to nonfrail participants. Furthermore, HR changes while performing a clinical test (e.g., the seated step test or the lying-to-standing orthostatic test) were decreased in the frail group compared to the nonfrail group. CONCLUSIONS: The current systematic review provides evidence that the cardiac ANS is impaired in frail compared to nonfrail older adults, as indicated by a reduction in the complexity of HR dynamics, reduced HRV, and reduced HR changes in response to daily activities. Four out of 6 included articles recruited only female participants, and in the other 2 articles the effect of gender on impairment of cardiac ANS was insufficiently investigated. Therefore, further studies are required to study the association between cardiac ANS impairments and frailty in males. Furthermore, HRV was studied only during static postures such as sitting, or without considering the level of activity as a potential confounder. Accordingly, simultaneous measurement of both physiological (i.e., HRV) and kinematic (e.g., using wearable sensor technology) information may provide a better understanding of cardiac ANS impairments with frailty while controlling for activity. PMID- 26159464 TI - Overcoming barriers to implementing patient-reported outcomes in an electronic health record: a case report. AB - In this case report, the authors describe the implementation of a system for collecting patient-reported outcomes and integrating results in an electronic health record. The objective was to identify lessons learned in overcoming barriers to collecting and integrating patient-reported outcomes in an electronic health record. The authors analyzed qualitative data in 42 documents collected from system development meetings, written feedback from users, and clinical observations with practice staff, providers, and patients. Guided by the Unified Theory on the Adoption and Use of Information Technology, 5 emergent themes were identified. Two barriers emerged: (i) uncertain clinical benefit and (ii) time, work flow, and effort constraints. Three facilitators emerged: (iii) process automation, (iv) usable system interfaces, and (v) collecting patient-reported outcomes for the right patient at the right time. For electronic health record integrated patient-reported outcomes to succeed as useful clinical tools, system designers must ensure the clinical relevance of the information being collected while minimizing provider, staff, and patient burden. PMID- 26159465 TI - WebDISCO: a web service for distributed cox model learning without patient-level data sharing. AB - OBJECTIVE: The Cox proportional hazards model is a widely used method for analyzing survival data. To achieve sufficient statistical power in a survival analysis, it usually requires a large amount of data. Data sharing across institutions could be a potential workaround for providing this added power. METHODS AND MATERIALS: The authors develop a web service for distributed Cox model learning (WebDISCO), which focuses on the proof-of-concept and algorithm development for federated survival analysis. The sensitive patient-level data can be processed locally and only the less-sensitive intermediate statistics are exchanged to build a global Cox model. Mathematical derivation shows that the proposed distributed algorithm is identical to the centralized Cox model. RESULTS: The authors evaluated the proposed framework at the University of California, San Diego (UCSD), Emory, and Duke. The experimental results show that both distributed and centralized models result in near-identical model coefficients with differences in the range [Formula: see text] to [Formula: see text]. The results confirm the mathematical derivation and show that the implementation of the distributed model can achieve the same results as the centralized implementation. LIMITATION: The proposed method serves as a proof of concept, in which a publicly available dataset was used to evaluate the performance. The authors do not intend to suggest that this method can resolve policy and engineering issues related to the federated use of institutional data, but they should serve as evidence of the technical feasibility of the proposed approach.Conclusions WebDISCO (Web-based Distributed Cox Regression Model; https://webdisco.ucsd-dbmi.org:8443/cox/) provides a proof-of-concept web service that implements a distributed algorithm to conduct distributed survival analysis without sharing patient level data. PMID- 26159466 TI - Engaging adolescents in a computer-based weight management program: avatars and virtual coaches could help. AB - OBJECTIVE: This research focuses on the potential ability of animated avatars (a digital representation of the user) and virtual agents (a digital representation of a coach, buddy, or teacher) to deliver computer-based interventions for adolescents' chronic weight management. An exploration of the acceptance and desire of teens to interact with avatars and virtual agents for self-management and behavioral modification was undertaken. MATERIALS AND METHODS: The utilized approach was inspired by community-based participatory research. Data was collected from 2 phases: Phase 1) focus groups with teens, provider interviews, parent interviews; and Phase 2) mid-range prototype assessment by teens and providers. RESULTS: Data from all stakeholder groups expressed great interest in avatars and virtual agents assisting self-management efforts. Adolescents felt the avatars and virtual agents could: 1) reinforce guidance and support, 2) fit within their lifestyle, and 3) help set future goals, particularly after witnessing the effect of their current behavior(s) on the projected physical appearance (external and internal organs) of avatars. Teens wanted 2 virtual characters: a virtual agent to act as a coach or teacher and an avatar (extension of themselves) to serve as a "buddy" for empathic support and guidance and as a surrogate for rewards. Preferred modalities for use include both mobile devices to accommodate access and desktop to accommodate preferences for maximum screen real estate to support virtualization of functions that are more contemplative and complex (e.g., goal setting). Adolescents expressed a desire for limited co user access, which they could regulate. Data revealed certain barriers and facilitators that could affect adoption and use. DISCUSSION: The current study extends the support of teens, parents, and providers for adding avatars or virtual agents to traditional computer-based interactions. Data supports the desire for a personal relationship with a virtual character in support of previous studies. The study provides a foundation for further work in the area of avatar-driven motivational interviewing. CONCLUSIONS: This study provides evidence supporting the use of avatars and virtual agents, designed using participatory approaches, to be included in the continuum of care. Increased probability of engagement and long-term retention of overweight, obese adolescent users and suggests expanding current chronic care models toward more comprehensive, socio-technical representations. PMID- 26159467 TI - Engineering of the thermodynamic properties of bilayer graphene by atomic plane rotations: the role of the out-of-plane phonons. AB - We investigated theoretically the specific heat of graphene, bilayer graphene and twisted bilayer graphene taking into account the exact phonon dispersion and density of states for each polarization branch. It is shown that contrary to a conventional belief the dispersion of the out-of-plane acoustic phonons - referred to as ZA phonons - deviates strongly from a parabolic law starting from the frequencies as low as ~100 cm(-1). This leads to the frequency-dependent ZA phonon density of states and the breakdown of the linear dependence of the specific heat on temperature T. We established that ZA phonons determine the specific heat for T <= 200 K while contributions from both in-plane and out-of plane acoustic phonons are dominant for 200 K <= T <= 500 K. In the high temperature limit, T > 1000 K, the optical and acoustic phonons contribute approximately equally to the specific heat. The Debye temperature for graphene and twisted bilayer graphene was calculated to be around ~1861-1864 K. Our results suggest that the thermodynamic properties of materials such as bilayer graphene can be controlled at the atomic scale by rotation of the sp(2)-carbon planes. PMID- 26159468 TI - Retraction Statement. Paper by Wang et al.: Oncology 2005;69:208-213 (DOI: 10.1159/000088332). PMID- 26159469 TI - Integrated algorithm for reconstruction of complex forms of Poland syndrome: 20 year outcomes. AB - BACKGROUND: The extent of breast and chest-wall deformity varies widely in Poland syndrome, and a variety of techniques are required to correct them. The aim of this study is to analyse our experience and long-term follow-up, and to propose an algorithmic approach to this complex deformity. PATIENTS AND METHODS: Retrospective case-note review from a prospectively maintained database was carried out on 37 patients. All patients treated between 1993 and 2013 were reviewed, and long-term outcome was assessed by an objective photographic documentation. The patients were invited to a photographic documentation, and the correlation between the subjective judgement and objective results in the late course was analysed. Based on our experience, we propose an algorithmic approach to this complex skeletal and soft-tissue deformity. RESULTS: Medical photographs were obtained from 32 patients (22 females and 10 males). The age range was 11-44 years. Significant reduction in asymmetry was possible in all patients. The mean follow-up time was 8.5 years (range, 2.2-20). The complex developmental defect involved the skin, subcutaneous tissue, breast, muscle, ribs and other skeletal abnormalities. The following treatments were applied alone or in combination: lipomodelling, liposuction, tissue expansion and implants, custom-made prosthesis, islanded pedicled latissimus dorsi muscle flaps, pedicled and free muscle-sparing transverse rectus abdominis flaps, prosthetic chest-wall reconstruction and various combinations including multistage procedures. Surgery on the contralateral breast in female and male patients was necessary in 22 patients (20 female and two male). Assessment of the late result by four non professionals (two females and two males) and one male plastic surgeon showed that the objective aesthetic results of the authors' reconstructions according to the proposed algorithm were sufficient. CONCLUSIONS: Poland syndrome is a complex developmental deformity in which several tissues are involved. It is crucial to have an armamentarium of techniques to tackle a variety of defects to meet patients' expectations, and to improve their quality of life. The clinical outcome of the currently presented algorithm proved beneficial in the decision process for the treatment of these congenital deformities. PMID- 26159470 TI - Funding analysis of bilateral autologous free-flap breast reconstructions in Australia. AB - INTRODUCTION: Bilateral breast reconstructions are being increasingly performed. Autologous free-flap reconstructions represent the gold standard for post mastectomy breast reconstruction but are resource intensive. This study aims to investigate the difference between hospital reimbursement and true cost of bilateral autologous free-flap reconstructions. METHODS: Retrospective analysis of patients who underwent bilateral autologous free-flap reconstructions at a single Australian tertiary referral centre was performed. Hospital reimbursement was determined from coding analysis. A true cost analysis was also performed. Comparisons were made considering the effect of timing, indication and complications of the procedure. RESULTS: Forty-six bilateral autologous free-flap procedures were performed (87 deep inferior epigastric perforators (DIEPs), four superficial inferior epigastric artery perforator flaps (SIEAs) and one muscle sparing free transverse rectus abdominis myocutaneous flap (MS-TRAM)). The mean funding discrepancy between hospital reimbursement and actual cost was $12,137 +/ $8539 (mean +/- standard deviation (SD)) (n = 46). Twenty-four per cent (n = 11) of the cases had been coded inaccurately. If these cases were excluded from analysis, the mean funding discrepancy per case was $9168 +/- $7453 (n = 35). Minor and major complications significantly increased the true cost and funding discrepancy (p = 0.02). CONCLUSION: Bilateral free-flap breast reconstructions performed in Australian public hospitals result in a funding discrepancy. Failure to be economically viable threatens the provision of this procedure in the public system. Plastic surgeons and hospital managers need to adopt measures in order to make these gold-standard procedures cost neutral. PMID- 26159471 TI - Parallel pocket incision: Less invasive surgical intervention for the treatment of intractable pressure ulcer with wound edge undermining. AB - BACKGROUND: The treatment of deep pressure ulcer with a wide wound edge undermining (pocket) is challenging, especially when conservative treatments are ineffective. As most patients with a pressure ulcer suffer from systemic comorbidities, invasive surgery cannot be performed on all patients, and less invasive treatment is required. METHODS: Less invasive surgical intervention to a deep pressure ulcer, parallel pocket incision (PPI), was performed on 10 patients with intractable pressure ulcers with a pocket formation. In PPI procedures, two parallel skin incisions were made to open up the deepest fold of the pocket and to preserve the skin overlying the pocket lesion; through the created incisions, the necrotic tissues around the deepest fold of the undermining could be easily removed, which facilitated spontaneous wound healing. Postoperative results and complications were evaluated. RESULTS: All PPI procedures were safely performed under local infiltration anesthesia without major postoperative complication; minor bleeding was seen intraoperatively in three patients, which could be easily controlled with electric cautery coagulation. Nine of 10 ulcers were cured after PPI, and one could not be followed up due to the patient's death non-related to the pressure ulcer. For the nine cured patients, the average time for cure was 14.9 weeks, and no recurrence was observed at postoperative 6 months. CONCLUSIONS: PPI is a simple, technically easy, and less invasive surgical intervention to an intractable pressure ulcer with a pocket, which can be safely performed under local infiltration anesthesia even on a patient with severe systemic comorbidities. PMID- 26159472 TI - Changes in flavour and microbial diversity during natural fermentation of suan cai, a traditional food made in Northeast China. AB - We measured changes in the main physical and chemical properties, flavour compounds and microbial diversity in suan-cai during natural fermentation. The results showed that the pH and concentration of soluble protein initially decreased but were then maintained at a stable level; the concentration of nitrite increased in the initial fermentation stage and after reaching a peak it decreased significantly to a low level by the end of fermentation. Suan-cai was rich in 17 free amino acids. All of the free amino acids increased in concentration to different degrees, except histidine. Total free amino acids reached their highest levels in the mid-fermentation stage. The 17 volatile flavour components identified at the start of fermentation increased to 57 by the mid-fermentation stage; esters and aldehydes were in the greatest diversity and abundance, contributing most to the aroma of suan-cai. Bacteria were more abundant and diverse than fungi in suan-cai; 14 bacterial species were identified from the genera Leuconostoc, Bacillus, Pseudomonas and Lactobacillus. The predominant fungal species identified were Debaryomyces hansenii, Candida tropicalis and Penicillium expansum. PMID- 26159473 TI - Influence of general stress-response alternative sigma factors sigma(S) (RpoS) and sigma(B) (SigB) on bacterial tolerance to the essential oils from Origanum vulgare L. and Rosmarinus officinalis L. and pulsed electric fields. AB - This study assessed the influence of general stress-response alternative sigma factors RpoS (sigma(S)) and SigB (sigma(B)) on tolerance of Escherichia coli (E. coli MG1655 and its isogenic mutant E. coli MG1655 DeltarpoS) and Listeria monocytogenes (L. monocytogenes EGD-e and its isogenic mutant L. monocytogenes EGD-e DeltasigB) to the essential oils (EOs) from Origanum vulgare L.-oregano (OVEO) and Rosmarinus officinalis L.-rosemary (ROEO), as well as the changes in tolerance of parental and DeltarpoS and DeltasigB mutant strains to OVEO, ROEO and pulsed electric fields (PEF) following overnight exposure to subinhibitory concentrations (1/2*minimum inhibitory concentration-MIC) of each tested EO. MIC values of OVEO and ROEO against the mutant cells were usually lower than those found against the parental cells. Survivor curves showed that mutant cells were more sensitive to these EOs than parental cells. The recovery of survivors in selective media showed a greater proportion of cells sublethally injured at their cell envelopes in the mutant strains compared with the parental strains. Induction of increased direct-tolerance to OVEO and ROEO or cross-tolerance to PEF was not observed after pre-exposure of parental and mutant cells to EOs. Otherwise, parental and mutant cells of E. coli and L. monocytogenes pre-exposed to OVEO or ROEO showed decreased tolerance when further treated with the homologous stressing agent at 2*MIC. Still, mutant cells pre-exposed to OVEO or ROEO showed lower tolerance to PEF than parental strains. These results showed the influence of sigma(S) and sigma(B) in tolerance of single strains of E. coli and L. monocytogenes, respectively, to OVEO and ROEO. Moreover, the deletion of sigma(S) and sigma(B) resulted in decreased tolerance to OVEO, ROEO or PEF in tested strains following exposure to OVEO or ROEO at a subinhibitory concentration. PMID- 26159474 TI - Stay-or-Leave Decision Making in Nonviolent and Violent Dating Relationships. AB - Data from the Toledo Adolescent Relationships Study were used to address how specific relationship dynamics, perceived alternatives, social support, and intimate partner violence (IPV) itself influenced breakups among respondents in nonviolent and violent dating relationships (n = 700). Both positive and negative relationship dynamics, perceived alternatives, and messages from significant others predicted whether individuals ended their relationships. In addition, these analyses indicated that violence was not associated with the odds of relationship termination. Among individuals reporting IPV (n = 245), similar factors influenced stay/leave decisions. Finally, the test for a threshold effect of IPV (n = 700) to determine whether higher levels of IPV experience "tipped the scales" and resulted in increased odds of relationship termination demonstrated that greater frequency of relationship violence was not associated with ending the relationship. PMID- 26159476 TI - Th22 cells in autoimmunity: a review of current knowledge. AB - Newly identified T helper cell 22 (Th22) is a subset of CD4+ T cells with specific properties apart from other known CD4+ T cell subsets. Th22 is obviously discrete from Th17 and Th1 subsets by production of interleukin (IL)-22 but not IL-17 or IFN-gamma, and also with distinguished expression of aryl hydrocarbon receptor (AHR) as the key transcription factor. This T helper subset, by producing pro-inflammatory cytokines such as IL-22 and tumor necrosis factor alpha (TNF-alpha), is implicated in the pathogenesis of inflammatory and autoimmune disorder. This review discusses the role of Th22 and its cytokine IL 22 in the immunopathogenesis of autoimmune disease including acute coronary syndrome, psoriasis, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, Behcet's disease, type 1 and 2 diabetes and immune thrombocytopenia. PMID- 26159475 TI - Prenatally Acquired Multiple Limb Ischemia in a Very Low Birth Weight Monochorionic Twin. AB - Limb ischemia is an extremely rare event occuring in monochorionic twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). The authors describe a case of TTTS and TAPS treated successfully using amnioreduction and laser ablation. However, severe ischemia of both lower extremities in the recipient twin developed after the fetal treatment. This serious complication was diagnosed on MRI in utero and confirmed postnatally. Elective amputation of the affected limbs was performed. The etiology of the disease remains unclear despite profound clinical and histopathological examinations; although the role of thromboembolism in monochorionic pregnancy seems to be most likely, this unique case of multiple limb ischemia with distinct macroscopic findings has not yet been described. PMID- 26159477 TI - Cross-reactivity of a new food ingredient, dun pea, with legumes, and risk of anaphylaxis in legume allergic children. AB - BACKGROUND: Legume allergy is the fifth food allergy in Europe. The dun pea (Pisum sativum sativum var. arvense), a pea belonging to the same subspecies as green pea, has been recently introduced as an ingredient in the human food industry. The aims of this study were to evaluate the cross-reactivity between dun pea and other legumes and to search for modification of allergenicity induced by food technologies. METHODS: A series of 36 patients with legume and/or peanut allergy was studied. They underwent skin tests to peanut and a panel of legumes including dun pea. Specific IgE to dun pea and cross-reactivity to peanut allergens, particularly to Ara h 1, were evaluated by ELISA. Proteins and allergens of different pea extracts were studied by SDS-PAGE and immunoblots. RESULTS: In France and Belgium, 7.7% of severe food anaphylaxis cases were due to legumes. Patients with isolated legume allergy had positive prick tests to dun pea, whereas patients with isolated peanut allergy had negative prick tests. Cross-reactivity between sIgE to peanut and dun pea was observed, and more frequently than expected (96%) peanut-allergic patients with legume sensitization or allergy had sIgE to Ara h 1. Analysis of dun pea allergens suggested that protein epitopes were presented differently in dun pea seeds, isolate and flour. CONCLUSIONS: This study identifies, for the first time, a risk of dun pea allergy in legume-allergic patients and in a subset of peanut-allergic patients. PMID- 26159478 TI - Anomalous cutaneous absorption of allergens as cause of skin prick testing adverse reactions in adult patients. Clinical and experimental evidence. AB - BACKGROUND: Paediatric age, active eczema and high number of allergens tested in poly-sensitized patients have been pinpointed as possible risk factors of systemic reactions by skin prick testing. As far as atopic eczema concerns, the higher penetration of the allergens into the skin because of the scraping or micro-injuries is an intuitive rationalization. Purpose of the present study is to provide documentary evidence that adverse reactions elicited by anomalous absorption of allergens can occur also in adult patients with apparently normal skin. METHODS: Report of some exemplifying clinical and experimental observations. Measuring the inoculum volume into impaired skin and its variability in relation to the variation of the chemical-physical characteristic of the solutions used for the tests by means of a method of direct assay based on the use of a gamma-camera. RESULTS: Localized impairments of the skin permeability can cause a significant increase in inoculum volume by prick-test. Critical amounts of allergens can be introduced into the skin because of the possibility of direct absorption, also without pricking, of allergy diagnostic solutions. The greater water content of the solutions used for prick-testing can significantly increase the inoculum volume. CONCLUSIONS: This study adds clinical and experimental evidences that localized impairments of permeability can occur in adult patients with apparently normal skin. Special precautions should be taken when a change of the drops' normal shape and cohesion is seen, because allergy prick-testing in such areas is potentially associated with increased risk of large local or systemic reactions. PMID- 26159479 TI - Can esophageal dilation be avoided in the treatment of severe esophageal stricture caused by eosinophilic esophagitis? AB - Eosinophilic esophagitis (EoE) is an inflammatory immune-mediated disease with predominant eosinophilic inflammation characterized by the presence of esophageal dysfunction symptoms. Treatment delay can be associated with disease complications, like esophageal strictures, that can justify the use of invasive procedures which are not deprived of side effects. We present a case report of a 14 year old child with severe esophageal stricture secondary to EoE, that was treated with topical and systemic corticosteroid before any invasive procedure was considered. After 26 weeks of medical treatment, significant improvement of esophageal dysfunction occurred with histological remission and stricture resolution. In patients with severe esophageal strictures secondary to EoE, the need for esophageal dilation procedures should be considered only after anti inflammatory treatment. PMID- 26159480 TI - Neighborhood Latino ethnic density and mortality among HIV-positive Latinos by birth country/region, Florida, 2005-2008. AB - OBJECTIVE: Lower mortality for Latinos has been reported in high Latino density areas. The objective was to examine the contribution of neighborhood Latino density to mortality among HIV-positive Latinos. METHODS: Florida HIV surveillance data for 2005-2008 were merged with the 2007-2011 American Community Survey data using zip code tabulation areas. Hazard ratios (HR) were calculated using multi-level weighted Cox regression and adjusted for individual-level factors and neighborhood poverty. RESULTS: Of 4649 HIV-positive Latinos, 11.8% died. There was no difference in mortality risk across categories of Latino ethnic density for Latinos as a whole. There were subgroup effects wherein mortality risk differed by ethnic density category for Latinos born in some countries/regions. Residing in an area with >=50% Latinos compared with <25% was associated with increased mortality risk for Latinos born in Puerto Rico (HR 1.67; 95% confidence interval [CI] [1.01-2.70]). Residing in an area where Mexicans were the majority Latino group was associated with increased mortality risk for Latinos born in Mexico (HR 3.57; 95% CI [1.43-10.00]). CONCLUSIONS: The survival advantage seen among the Latino population in high Latino density areas was not seen among HIV-positive Latinos. Research is needed to determine if this may be related to stigma or another mechanism. PMID- 26159481 TI - A computational view on the significance of E-ring in binding of (+)-arisugacin A to acetylcholinesterase. AB - A computational docking study of a series of de novo structural analogs of the highly potent, non-nitrogen containing, acetylcholinesterase inhibitor (+) arisugacin A is presented. In direct comparison to the recently reported X-ray single-crystal structure of (+)-territrem B bound hAChE, the modeling suggests that there is a unique conformational preference for the E-ring that is responsible for the superior inhibitory activity of (+)-arisugacin A against hAChE relative to (+)-territrem B, and that substitutions on the E-ring also play an important role in the protein-ligand interaction. PMID- 26159483 TI - The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation. AB - A facile method via 1,3-dipolar cycloaddition of substituted benzylidene-2 phenyloxazolone under mild conditions with azomethine ylides, which were generated in situ by a decarboxylative route from a common set of diverse isatins and amino acid derivatives was developed for a 15-membered library of regio- and stereoselective oxazolones-grafted spirooxindole-pyrrolidine, pyrrolizidines and pyrrolothiazoles. After screening their cytotoxic activities against a spectrum of cell-lines, compound 4h was identified as potent antitumor agent and inducing apoptosis. The present study has provided an effective entry to rapidly construct a chemical library of oxazolones-grafted spirooxindoles and developed a good lead compound for subsequent optimization. PMID- 26159484 TI - Dendritic hexadecapeptide as a cathepsin B degradable carrier for delivery of HSP90 inhibitor. AB - Biodegradable vehicles that degrade specifically at tumor sites are highly desirable since they can cause selective exposure of highly toxic drugs at tumor sites whereas keep the conjugates stable during blood circulation. Here, we evaluate the utility of a dendritic hexadecapeptide comprised of four arms, each having a tetrapeptide sequence recognized by an enzyme cathepsin B as a carrier system for heat shock protein 90 (HSP90) inhibitor geldanamycin (GDM). We report the synthesis of a carrier having GDM conjugated to the terminal end of each arm (>55% wt/wt drug). We further report the stability of the GDM containing peptidic dendrimer in various buffers and in the presence of serum along with its ability to release free drug in the presence of cathepsin B, the enzyme overexpressed in a variety of tumors. Using androgen-independent prostate cancer cell line (DU 145) we further demonstrate that the geldanamycin containing peptidic dendrimer has antiproliferative property similar to the free drug derivative. PMID- 26159485 TI - Ultrasound-guided contrast enema for meconium obstruction in very low birth weight infants: Factors that affect treatment success. AB - INTRODUCTION: This study aimed to assess the therapeutic results of ultrasound (US)-guided water-soluble contrast enema in very low birth weight (VLBW) preterm infants (<1,500 g) with meconium obstruction and to study factors that affect therapeutic results. METHODS: This study included a total of 33 consecutive VLBW infants with clinically diagnosed meconium obstruction underwent US-guided water soluble contrast enema, from April 2007 to March 2014. Patients were classified into two groups based on to procedure outcome: the success group (evacuation of the meconium plug resolution followed by improved bowel distention within 2 days of the procedure, without additional interventions), and the failure group (the contrast enema failed to relieve the obstruction, or other procedure-related complications occurred). Patient- and mother-related clinical factors and procedure-related factors were compared between both groups. RESULTS: Overall success rate was 54.5%, with 18 successful (M:F=10:8), and 15 failure (M:F=7:8) cases. When compared with the failure group, the success group patients showed statistically significant older gestational age (29(+1) vs. 27 weeks; p=0.028), larger birth weight (1023.1g vs. 790.3g; p=0.048), and higher body weight on the day of the procedure (1036.2g vs. 801.6g, p=0.049). However, no statistically significant differences were seen between other patient and maternal factors. Among the procedure-related factors, retrial of contrast injection during the procedure was associated with significantly higher success than the single trial (p=0.027). The presence of refluxed contrast into the distal ileum was the statistically significant predictor for success of the procedure (p=0.038). There were three cases of bowel perforation (9.1% per person). CONCLUSION: US-guided water-soluble contrast enema in VLBW infants with meconium obstruction showed a 54.5% success rate and a 9.1% perforation rate per person. Among the procedure related factors, retrial of contrast injection during the procedure and the presence of refluxed contrast into the distal ileum were related to the success of the procedure. PMID- 26159482 TI - Mitochondrial targeted beta-lapachone induces mitochondrial dysfunction and catastrophic vacuolization in cancer cells. AB - Mitochondria play important roles in tumor cell physiology and survival by providing energy and metabolites for proliferation and metastasis. As part of their oncogenic status, cancer cells frequently produce increased levels of mitochondrial-generated reactive oxygen species (ROS). However, extensive stimulation of ROS generation in mitochondria has been shown to be able to induce cancer cell death, and is one of the major mechanisms of action of many anticancer agents. We hypothesized that enhancing mitochondrial ROS generation through direct targeting of a ROS generator into mitochondria will exhibit tumor cell selectivity, as well as high efficacy in inducing cancer cell death. We thus synthesized a mitochondrial targeted version of beta-lapachone (XJB-Lapachone) based on our XJB mitochondrial targeting platform. We found that the mitochondrial targeted beta-lapachone is more efficient in inducing apoptosis compared to unconjugated beta-lapachone, and the tumor cell selectivity is maintained. XJB-Lapachone also induced extensive cellular vacuolization and autophagy at a concentration not observed with unconjugated beta-lapachone. Through characterization of mitochondrial function we revealed that XJB-Lapachone is indeed more capable of stimulating ROS generation in mitochondria, which led to a dramatic mitochondrial uncoupling and autophagic degradation of mitochondria. Taken together, we have demonstrated that targeting beta-lapachone accomplishes higher efficacy through inducing ROS generation directly in mitochondria, resulting in extensive mitochondrial and cellular damage. XJB Lapachone will thus help to establish a novel platform for the design of next generation mitochondrial targeted ROS generators for cancer therapy. PMID- 26159486 TI - [Vascular relationships of the right great splanchnic nerve in the thorax]. AB - AIM: The surgical assumption of responsibility of the pancreatic pain requires either a truncular coelioscopic or radicular neurectomy of greater splanchnic nerves (gsn). The goal of our work is to describe the way and relations of the right gsn which are variable and rarely described. This constitutes an undeniable peroperational hemorrhagic risk during splanchnicectomy. MATERIAL AND METHODS: After a double side thoracotomy and a bilateral sterno-clavicular desarticulation on 15 adult cadaveric subjects preserved by method of Winckler we removed the sterno-costal drill plate as well as the ventral rib arch and proceeded to a mediastinal evisceration of the thorax. Then we respected only the thoracic aorta and the oesophagus, the azygos venous system, the thoracic duct and the thoracic sympathetic chain. In some of the subjects, the azygos vein was injected (after catheterization of its stick) using gelatine coloured with blue paint. We studied the way and vascular relations of the right gsn. We measured the transverse distances between the origin of the gsn on one hand and the longitudinal axes of the azygos vein and the thoracic duct on the other hand. RESULTS: The relations of the right gsn trunk during its way related to the azygos vein in particular its constitutive origin and its affluents: ascending lumbar vein and twelfth intercostal vein. Sometimes the thoracic duct even a lymphatic node was near the gsn in the posterior infra-mediastinal space. A classification of the way and vascular relations of the right gsn in the thorax identified 3 anatomical types. The average distances separating the right gsn on one hand from the azygos vein and the thoracic duct on the other hand were respectively 5.7 mm and 11.2 mm. CONCLUSION: The vascular relations of the right gsn are very variable from one subject to another but primarily venous, sometimes lymphatic. They concerned the great thoracic vessels whose respect is essential in particular at the time of mini-invasive access procedure for a coelioscopic splanchnicectomy. PMID- 26159487 TI - Triglyceride sensing in the reward circuitry: A new insight in feeding behaviour regulation. AB - In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Obesity often involves a behavioural component in which, similar to drugs abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. The hypothalamus is one of the primary integration sites of circulating energy-related signals like leptin or ghrelin and is therefore considered as one of the main central regulators of energy balance. However, food intake is also modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a key actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable food and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the reward circuitry. PMID- 26159488 TI - Two persistent organic pollutants which act through different xenosensors (alpha endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose metabolism. AB - Individuals, typically, are exposed to mixtures of environmental xenobiotics affecting multiple organs and acting through different xenosensors and pathways in species and cell-type specific manners. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and alpha-endosulfan are Persistent Organic Pollutants (POPs) and endocrine disruptors which act through different xenosensors and accumulate in the liver. Our objective in this HEALS study was to investigate the effects of the mixture of these POPs on gene expression in a human-derived hepatocyte cell line, HepaRG. We found that, in spite of having largely uncorrelated effects, TCDD and alpha-endosulfan, when mixed, alter the expression of genes. The combined effects of the mixture of the POPs significantly altered the expression of 100 genes (42 up- and 58 down-regulated) whereas the same concentration of either POP alone did not alter significantly the expression of these genes. For 32 other genes, selective inhibitory crosstalk between TCDD and alpha-endosulfan was observed. One of the POPs inhibited the effect, on gene expression, of the other in the mixture although, when used alone, that POP did not affect expression. The expression of another 82 genes was significantly altered (up- or down-regulated) by a single POP. The addition of the second POP either increased, in the same direction, the effect on gene expression or had no further effect. At low concentrations (0.2 nM TCDD and 1 MUM alpha-endosulfan), the POPs still had significant effects and the levels of expression of the corresponding proteins were found to be affected for some genes. Particularly striking was the 80-90% inhibition, by the mixture, of the expression of a number of genes of several hepatic intermediary metabolic pathways (glycerolipid metabolism, FXR/RXR activation, glycolysis/gluconeogenesis, retinoid and bile acid biosynthesis), whereas each pollutant alone had only a moderate effect. PMID- 26159489 TI - MicroRNA-155 Promotes Atherosclerosis Inflammation via Targeting SOCS1. AB - AIMS: Accumulating evidence suggests that atherosclerotic progression depends on persistent and chronic inflammation in the arterial walls. MicroRNA-155 is reportedly involved in cardiovascular disease and has been implicated as a pro inflammation regulator. Although some researchers have focused on microRNA-155 as an atherosclerosis regulator, the mechanisms by which microRNA-155 functions as a putative pro-atherosclerosis microRNA are largely unknown. This study aims to analyze microRNA-155's effects on atherosclerotic inflammation and to explore its mechanism. METHODS: MicroRNA-155's effects on atherosclerotic inflammation were observed along with the expression and activity levels of SOCS1, STAT3 and NF kappaB though microRNA-155 inhibition or overexpression. RESULTS: Highly expressions of microRNA-155 in oxLDL-stimulated macrophages and atherosclerosis mice were inversely correlated with SOCS1 expression. Ectopic microRNA-155 overexpression significantly promoted inflammatory cytokine and chemokine production and atherosclerosis progression. We then observed microRNA-155's functional role in the atherosclerotic pathophysiological process in vivo and in vitro. The observation revealed that by enhancing STAT3 and NF-kappaB signaling and facilitating immune inflammation by targeting SOCS1, microRNA-155 plays a promotable role in atherosclerosis progression. CONCLUSIONS: microRNA-155 works as a promoter in the atherosclerotic procession. Its mechanism may include enhancing inflammatory response in atherosclerosis by increasing STAT3 and NF kappaB signaling via targeting SOCS1. PMID- 26159490 TI - The Role of Androgen Under Normal and Pathological Conditions in Sebaceous Glands: The Possibility of Target Therapy. AB - The androgen receptor plays a pivotal role in the sebaceous glands. Its primary function is to stimulate cell proliferation and differentiation in the sebaceous and its associate with acne. Previous studies have demonstrated expression of AR and steroidogenic enzymes in normal sebaceous glands and in all sebaceous disorders present evidence that androgen receptor may be a sensitive marker of sebaceous differentiation. It has been previously suggested that AR and steroidogenic enzymes immunohistochemistry may be useful particularly in identifying poorly sebaceous carcinoma. This review will provide an overview of the AR functions in the sebaceous glands and discussion of the therapeutic targets in acne and carcinoma. PMID- 26159491 TI - Recanalization Rate and Clinical Outcome in Acute Carotid-T Occlusion. AB - BACKGROUND: Acute carotid-T occlusion results in both low recanalization rates and poor outcomes. We investigated clinical outcomes and recanalization in a rare case of thrombolytic therapy. METHODS: A consecutive series of patients with acute carotid-T occlusion who were treated with either bridging intravenous (IV) plus intra-arterial (IA) thrombolysis or IA alone were analyzed. Complete recanalization was defined as a thrombolysis in cerebral infarction (TICI) grade of 3. A favorable outcome was defined as a modified Rankin Scale (mRS) score of <=2. RESULTS: Of the 40 patients, 6 (15%) had favorable outcomes, and 34 (85%) had poor outcomes. Favorable outcomes were significantly associated with a lower National Institutes of Health Stroke Scale (NIHSS) score after revascularization treatment and higher rates of complete recanalization (p < 0.01, p < 0.024, respectively). Complete recanalization was achieved in all patients with favorable clinical outcomes and 5 (83%) patients had received combined IV/IA thrombolysis (p = 0.381). CONCLUSIONS: The results suggest that complete recanalization for acute carotid-T occlusion improves clinical outcomes. In that regard, bridging IV/IA thrombolysis may be more efficacious than IA alone. PMID- 26159492 TI - The specificity of immune priming in silkworm, Bombyx mori, is mediated by the phagocytic ability of granular cells. AB - In the past decade, the phenomenon of immune priming was documented in many invertebrates in a large number of studies; however, in most of these studies, behavioral evidence was used to identify the immune priming. The underlying mechanism and the degree of specificity of the priming response remain unclear. We studied the mechanism of immune priming in the larvae of the silkworm, Bombyx mori, and analyzed the specificity of the priming response using two closely related Gram-negative pathogenic bacteria (Photorhabdus luminescens TT01 and P. luminescens H06) and one Gram-positive pathogenic bacterium (Bacillus thuringiensis HD-1). Primed with heat-killed bacteria, the B. mori larvae were more likely to survive subsequent homologous exposure (the identical bacteria used in the priming and in the subsequent challenge) than heterologous (different bacteria used in the priming and subsequent exposure) exposure to live bacteria. This result indicated that the B. mori larvae possessed a strong immune priming response and revealed a degree of specificity to TT01, H06 and HD-1 bacteria. The degree of enhanced immune protection was positively correlated with the level of phagocytic ability of the granular cells and the antibacterial activity of the cell-free hemolymph. Moreover, the granular cells of the immune-primed larvae increased the phagocytosis of a previously encountered bacterial strain compared with other bacteria. Thus, the enhanced immune protection of the B. mori larvae after priming was mediated by the phagocytic ability of the granular cells and the antibacterial activity of the hemolymph; the specificity of the priming response was primarily attributed to the phagocytosis of bacteria by the granular cells. PMID- 26159493 TI - Uroflowmetry with pelvic floor electromyography: inter-rater agreement on diagnosis of pediatric non-neurogenic voiding disorders. AB - INTRODUCTION: Uroflowmetry with electromyography (uroflow-EMG) is commonly used for evaluation of lower urinary tract (LUT) function in children. Diagnostic criteria based largely on uroflow-EMG findings have previously been proposed for several conditions collectively termed non-neurogenic voiding disorders (NNVDs). These include dysfunctional voiding (DV), idiopathic detrusor overactivity disorder (IDOD), detrusor underutilization disorder (DUD), and primary bladder neck dysfunction (PBND). It is unknown whether practitioners with varying levels of training and experience can apply the diagnostic criteria for these conditions with a high level of consistency. OBJECTIVE: To assess inter-rater agreement on diagnosis of NNVDs using uroflow-EMG studies. STUDY DESIGN: Six raters performed post hoc evaluation of 84 uroflow-EMG studies and associated clinical data from children with symptoms of LUT dysfunction and no evidence of neurologic or anatomic abnormalities. Each rater was asked to categorize the uroflow-EMG studies as being consistent with DV, IDOD, DUD, PBND, or normal/unclassifiable. A consensus diagnosis was noted for studies on which at least four raters agreed. Inter-rater agreement was assessed via calculation of unweighted Fleiss' kappa statistics. RESULTS: Overall inter-rater agreement on NNVD diagnoses was moderate (kappa 0.46, 95% CI 0.38-0.54). Agreement between individual raters ranged from 0.33 (fair) to 0.74 (substantial) (Figure). There was no consensus on diagnosis for 20 patients (24%). DISCUSSION: Several factors may contribute to inter-rater disagreement on diagnosis of NNVDs. These include instances where patients satisfy one criterion for a particular diagnosis while missing others - or have findings consistent with more than one diagnosis. Strategies to address this may involve simplifying the diagnostic criteria, developing a clear algorithm that prioritizes certain criteria, and/or allowing assignment of multiple diagnoses. Practitioners could also benefit from standardized education regarding the diagnostic criteria for NNVDs. Potential limitations of this analysis included the use of just one uroflow-EMG study per patient in almost all cases. Also, the raters had variable levels of previous experience using the diagnostic criteria for NNVDs, and it is possible that they were not always applied as originally intended. If this were the case, it would support development of a standardized education tool to facilitate practitioner understanding and application of the criteria. CONCLUSIONS: Uroflow-EMG has shown promise for improving clinical management of NNVDs associated with pediatric LUT dysfunction. However, inter rater agreement on NNVD diagnoses using current criteria is suboptimal. Various mechanisms should be explored to improve consistency in practitioners' diagnosis of NNVDs. PMID- 26159495 TI - Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells. AB - A20, also known as tumor necrosis factor-alpha (TNFalpha)-induced protein 3 (TNFAIP3), has been identified as a key regulator of cell survival in many solid tumors. However, little is known about the protein expression level and function of A20 in acute lymphoblastic leukemia (ALL). In this study, we found that A20 is up-regulated in ALL patients and several cell lines. Knockdown of A20 in Jurkat, Nalm-6, and Reh cells resulted in reduced cell proliferation, which was associated with cell cycle arrest. Phospho-ERK (p-ERK) was also down-regulated, while p53 and p21 were up-regulated in A20 knockdown cells. In addition, A20 knockdown induced apoptosis in Jurkat and Reh cells and enhanced the sensitivity of these cell lines to chemotherapeutic drugs. These results indicate that A20 may stimulate cell proliferation by regulating cell cycle progression. A20 inhibited apoptosis in some types of ALL cells, thereby enhancing their resistance to chemotherapy. This effect was abolished through A20 silencing. These findings suggest that A20 may contribute to the pathogenesis of ALL and that it may be used as a new therapeutic target for ALL treatment. PMID- 26159496 TI - The additional costs of catheter-related bloodstream infections in intensive care units. AB - PURPOSE: The additional costs of health care-associated infections vary depending on the reimbursement systems of different countries. We estimated the additional costs of central venous catheter-related bloodstream infections (CVC-CRBSI) in Japan, which has a universal health insurance system covering all citizens. METHODS: We conducted a retrospective matched case-control study. Twenty-two patients with CVC-CRBSI were identified among 2,148 patients treated between October 2011 and May 2014 in the intensive care unit of Tokyo Medical University Hospital (1,015 beds). Twenty-two matched controls were selected on the basis of 5 criteria. The drug and medical material costs and technical fees incurred from the date of catheter insertion until hospital discharge were examined using a fee for-service system. The additional costs of CVC-CRBSI were calculated as the difference between the costs of cases and controls. The contribution of antimicrobial drugs and the causative microorganism to the additional drug costs were also assessed. RESULTS: The additional costs of CVC-CRBSI were estimated at $57,090 per case. Antimicrobial agents comprised only about 10% of the additional drug costs. The additional costs of Candida infection were almost twice those of CVC-CRBSI caused by other microorganisms. CONCLUSIONS: The additional costs of CVC-CRBSI in Japan were estimated at $57,090 per case. PMID- 26159497 TI - Incidence of occupational exposure to blood and body fluids and measures taken by health care workers before and after exposure in regional hospitals of a developing country: a multicenter study. AB - This cross-sectional study was conducted on 371 health care workers working in government hospitals in the Northern Khorasan province of Iran. Exposure to sharp objects was 44% and 31% of participants had a history of being in contact with blood or body fluids of patients. Among health care workers who had needlestick injuries, 82 had a positive hepatitis B surface antibody titer measured after injury. PMID- 26159498 TI - Quantification of hand hygiene compliance in anesthesia providers at a tertiary care center in northern India. AB - Hand hygiene (HH) compliance continues to remain poor amongst anesthetists mainly because of multitasking and the need for repeated HH. We aimed to quantify HH compliance amongst anesthesia providers while performing anesthesia-related procedures inside operating rooms. The observations for HH before and after procedures, including placement of intravenous cannula, intubation, central line placement, arterial line placement, and neuraxial and peripheral nerve block, were made by a single observer in operating rooms where elective surgeries are carried out. The overall compliance of all health care workers was 39.6%. Resident physicians were less likely to be compliant than consultant physicians and there was significant variation in procedure-related HH with maximum compliance before neuraxial block (100%) followed by arterial line placement (93.7%), central line insertion (86.7%), and peripheral nerve block (80%) (P < .001). The compliance after performing the above procedures was <50% for all procedures. PMID- 26159499 TI - Clostridium difficile infections before and during use of ultraviolet disinfection. AB - BACKGROUND: We previously reported a significant decrease in hospital-acquired (HA) Clostridium difficile infection (CDI) coincident with the introduction of pulsed xenon ultraviolet light for room disinfection (UVD). The purpose of this study was to evaluate CDI cases in greater detail to understand the effect of UVD. METHODS: CDI rates (HA and community acquired [CA]), CDI patient length of stay, room occupancy, and number of days between a CDI case in a room and an HA CDI case in the same room were studied for the first year of UVD compared with the 1-year period pre-UVD. RESULTS: Compared with pre-UVD, during UVD, HA CDI was 22% less (P = .06). There was a 70% decrease for the adult intensive care units (ICUs) (P < .001), where the percentage of room discharges with UVD was greater (P < .001). During UVD, CA CDI increased by 18%, and length of stay of all CDI cases was lower because of the greater proportion of CA CDI. No significant difference was found in days to HA CDI in rooms with a prior CDI occupant. CONCLUSION: These data suggest that UVD contributed to a reduction in ICU acquired CDI where UVD was used for a larger proportion of discharges. Evaluation of UVD should include data for hospitalized CA CDI cases because these cases may impact the HA CDI rate. PMID- 26159500 TI - Bacteriuria and urinary tract infection after female urodynamic studies: risk factors and microbiological analysis. AB - BACKGROUND: This study was conducted to determine risk factors for infectious complications after urodynamic study (UDS) in women, which can assist clinicians in identifying high-risk subjects who would benefit from antibiotic prophylaxis before UDS. METHODS: In this prospective cohort study, we studied 232 women who underwent UDS at Santa Casa de Sao Paulo School of Medical Sciences between June 2013 and June 2014. Women ranging in age from 26 to 84 years who had urinary incontinence, pelvic organ prolapse, or voiding dysfunction were required to collect urine samples at 7 days before, on the day of, and 3-5 days after UDS. Urine cultures with >100,000 CFU/mL were considered positive. Risk factors associated with bacteriuria and urinary tract infection (UTI) after UDS were evaluated using multivariate analysis with multiple logistic regression. RESULTS: Two hundred thirty-two out of 257 women were subjected to further analysis. The incidence of bacteriuria, transient bacteriuria, and UTI after UDS was 11.6%, 7.3%, and 4.3%, respectively. On multivariate analysis, hypothyroidism (P = .04), body mass index (BMI) >30 (P = .025), and advanced pelvic organ prolapse (P = .021) were associated with a significantly increased risk of bacteriuria; however, only BMI >30 (P = .02) was associated with an increased risk for UTI. CONCLUSIONS: The rate of infectious complications after UDS was low, and advanced pelvic organ prolapse and hypothyroidism increased the risk for bacteriuria. However, only BMI >30 was associated with bacteriuria and UTI after UDS. PMID- 26159501 TI - Empirical therapies among adults hospitalized for community-acquired upper urinary tract infections: A decision-tree analysis of mortality, costs, and resistance. AB - BACKGROUND: Poor outcomes occur when patients with serious infections receive antibiotics to which the organisms are resistant. METHODS: Decision trees simulated in-hospital mortality, costs, incremental cost-effectiveness ratio per life year saved, and carbapenem resistance according to 3 empirical antibiotic strategies among adults hospitalized for community-acquired (CA) upper urinary tract infections (UTIs): ceftriaxone (CRO) plus gentamicin (GM) in the intensive care unit (ICU), imipenem (IMP), and individualized choice (IMP or CRO) based on clinical risk factors for CA- extended-spectrum beta-lactamase (ESBL). RESULTS: The estimated prevalence of CA-ESBL on admission was 5% (range, 1.3%-17.6%); 3% and 97% were admitted to the ICU and medical ward (MW), respectively. In the ICU, CRO plus GM was dominated; IMP was cost-effective (incremental cost-effectiveness ratio: ?4,400 per life year saved compared with individualized choice). In the MW, IMP had no impact on mortality and was less costly (-?142 per patient vs CRO, -?38 vs individualized choice). The dominance of IMP was consistent in sensitivity analyses. Compared with CRO, colonization by carbapenem-resistant pathogens increased by an odds ratio of 4.5 in the IMP strategy. CONCLUSION: Among the ICU patients, empirical IMP therapy reduces mortality at an acceptable cost. Among MW patients, individualized choice or CRO is preferred to limit carbapenem resistance at a reasonable cost. PMID- 26159502 TI - Retrospective cohort study of inappropriate piperacillin-tazobactam use for lower respiratory tract and skin and soft tissue infections: Opportunities for antimicrobial stewardship. AB - BACKGROUND: Patients with skin and skin structure infections (SSTIs) and lower respiratory tract infections (LRTIs) are frequently prescribed piperacillin tazobactam (TZP) on hospital admission. Inappropriate broad-spectrum coverage may be associated with patient harm, excess expenditure, and escalating rates of antimicrobial resistance. METHODS: Patients who received empirical TZP for a diagnosis of LRTI or SSTI from January 1-June 30, 2012, were identified retrospectively. Clinical and antimicrobial data were systematically collected from electronic hospital information systems. Using published guidelines, microbiologic results, and individual clinical responses, the appropriateness of TZP use was assessed. Drug utilization after potential standard audit of therapy on day 3 was also evaluated. RESULTS: We reviewed 60 patients with SSTI and 169 patients with LRTI. Inappropriate empirical TZP therapy was found in 41.7% in those with SSTI, and a further 15% had inappropriate continuation of therapy. In LRTI patients, 38.3% received inappropriate empirical TZP, and 10.3% of the treatment courses were continued inappropriately. Community-acquired pneumonia was the most frequent diagnosis where TZP was used inappropriately (96%). A day 3 audit of therapy may have saved 256 days of TZP. CONCLUSION: In our institution, inappropriate empirical TZP is common for community-onset infections of mild to moderate severity. A prospective audit and feedback program may be a strategy to reduce inappropriate use of TZP as empirical therapy. PMID- 26159503 TI - Additive impact of pneumococcal conjugate vaccines on pneumonia and empyema hospital admissions in England. AB - OBJECTIVES: A wider spectrum 13-valent pneumococcal vaccine (PCV13) replaced PCV7 in the child immunization schedule in England from 2010. We assessed the additional impact of PCV13 over PCV7 on all-cause pneumonia and empyema admissions. METHODS: We extracted Hospital Episode Statistics data from 2001 to 2014 on all-cause pneumonia (ICD-10 codes J12-18) and empyema admissions (J86.0, J86.9) for children <16 years in England. Trend analysis and rate ratios (RR) were calculated comparing the Pre-vaccine era to September 2006, the PCV7 era and the PCV13 era from April 2010. RESULTS: Annual hospital admissions for pneumonia and empyema were increasing in the Pre-vaccine era peaking in 2005 at 15,733 pneumonia and 382 empyema cases (158.6 and 3.9 per 100,000 children, respectively). These rates fell following PCV7 introduction in 2006 but began to climb soon afterwards until PCV13 was introduced. By 2013, admission rates for pneumonia and empyema were 102.2 and 1.9 per 100,000 children, respectively. We found no added benefit of PCV13 over PCV7 on pneumonia admissions following PCV13 introduction but there was a significant decrease in empyema admissions in children aged <2 years (RR 0.58; 95% CI 0.34-0.99). CONCLUSIONS: Additional serotypes covered by PCV13 may be more important in the aetiology of empyema and invasive disease than as a cause of uncomplicated pneumonia. PMID- 26159504 TI - Optimising filtering parameters for a 3D motion analysis system. AB - In the analysis of movement data it is common practice to use a low-pass filter in order to reduce measurement noise. However, the choice of a cut-off frequency is typically rather arbitrary. The aim of the present study was to evaluate a new method to find the optimal cut-off frequency for filtering kinematic data. In particular, we propose to use rigid marker clusters to determine the dynamic precision of a given 3D motion analysis system, and to use this precision as criterion to find the optimal cut-off frequency for filtering the data. We tested this method using a model-based approach in a situation in which measurement noise is a serious concern, namely the registration of the kinematics of swimming using a video-based motion analysis system. For the model data we found that filtering the data with a single cutoff frequency of 6Hz under some conditions decreased the accuracy of the reconstruction of the kinematics compared to using the unfiltered data. If the cut-off frequency was used that yielded optimal dynamic precision, then the accuracy improved by 29% compared to using raw data irrespective of the cluster position, close to the optimal accuracy improvement of 30%. We confirmed in an experiment that the cut-off frequency at which optimal precision was found varied between cluster positions and subjects, similar to the results obtained with the model. We conclude that 3D motion analysis systems can be made more accurate by optimising the cut-off frequency used in filtering the data with regard to their precision. Furthermore, the dynamic precision method seems useful to evaluate the effect of various filtering procedures. PMID- 26159505 TI - (18)F-FDG PET/CT for the detection of large vessel vasculitis in patients with polymyalgia rheumatica. AB - PURPOSE: Polymyalgia rheumatica (PMR) may present together with large vessel vasculitis (LVV), and frequently requires a more intensive therapy. The aim of the study was to evaluate the impact of (18)F-FDG PET/CT in the diagnosis and management of LVV associated to PMR. MATERIAL AND METHODS: This prospective study included 40 consecutive patients (27 women/13 men, 68.10+/-10.27 years) with PMR and suspicion of associated LVV submitted for (18)F-FDG PET/CT. A PET/CT scan was obtained 180 min after (18)F-FDG intravenous injection. A visual analysis was performed on the images. Five vascular regions were evaluated: supra-aortic trunks (SAT), thoracic aorta (TA), abdominal aorta (AA), iliac arteries (IA), and femoral/tibioperoneal arteries (FTA). The intensity of uptake was graded from 0 to 3. A final diagnosis of LVV was established in 26/40 patients (65%). RESULTS: In the 26 patients with a diagnosis of LVV, the highest intensity of (18)F-FDG uptake was observed in the TA, SAT, and FTA. All of these patients showed uptake at the TA, with grade 2 and 3 in most cases. In 4 of the 14 patients without LVV, no uptake was observed in any vascular region, and in the other 10 patients only a grade 1 uptake was observed in 1 or to 2 territories. Out of the 20 treated LVV patients, (18)F-FDG PET/CT led to a therapeutic change in 17 (85%). CONCLUSION: (18)F-FDG PET/CT was useful in identifying patients with LVV associated to PMR. The detection of vascular inflammation had an important impact, and led to a change of treatment in a high percentage of patients with LVV. PMID- 26159506 TI - Gastric S-nitrosothiol formation drives the antihypertensive effects of oral sodium nitrite and nitrate in a rat model of renovascular hypertension. AB - Many effects of nitrite and nitrate are attributed to increased circulating concentrations of nitrite, ultimately converted into nitric oxide (NO(*)) in the circulation or in tissues by mechanisms associated with nitrite reductase activity. However, nitrite generates NO(*) , nitrous anhydride, and other nitrosating species at low pH, and these reactions promote S-nitrosothiol formation when nitrites are in the stomach. We hypothesized that the antihypertensive effects of orally administered nitrite or nitrate involve the formation of S-nitrosothiols, and that those effects depend on gastric pH. The chronic effects of oral nitrite or nitrate were studied in two-kidney, one-clip (2K1C) hypertensive rats treated with omeprazole (or vehicle). Oral nitrite lowered blood pressure and increased plasma S-nitrosothiol concentrations independently of circulating nitrite levels. Increasing gastric pH with omeprazole did not affect the increases in plasma nitrite and nitrate levels found after treatment with nitrite. However, treatment with omeprazole severely attenuated the increases in plasma S-nitrosothiol concentrations and completely blunted the antihypertensive effects of nitrite. Confirming these findings, very similar results were found with oral nitrate. To further confirm the role of gastric S-nitrosothiol formation, we studied the effects of oral nitrite in hypertensive rats treated with the glutathione synthase inhibitor buthionine sulfoximine (BSO) to induce partial thiol depletion. BSO treatment attenuated the increases in S-nitrosothiol concentrations and antihypertensive effects of oral nitrite. These data show that gastric S-nitrosothiol formation drives the antihypertensive effects of oral nitrite or nitrate and has major implications, particularly to patients taking proton pump inhibitors. PMID- 26159507 TI - Perfluorooctanoic acid exposure induces endoplasmic reticulum stress in the liver and its effects are ameliorated by 4-phenylbutyrate. AB - Perfluoroalkyl acids (PFAAs) are a group of widely used anthropogenic compounds. As one of the most dominant PFAAs, perfluorooctanoic acid (PFOA) has been suggested to induce hepatotoxicity and several other toxicological effects. However, details on the mechanisms for PFOA-induced hepatotoxicity still need to be elucidated. In this study, we observed the occurrence of endoplasmic reticulum (ER) stress in mouse livers and HepG2 cells after PFOA exposure using several familiar markers for the unfolded protein response (UPR). ER stress in HepG2 cells after PFOA exposure was not significantly influenced by autophagy inhibition or stimulation. The antioxidant defense system was significantly disturbed in mouse livers after PFOA exposure, and reactive oxygen species (ROS) were increased in cells exposed to PFOA for 24 h. However, N-acetyl-L-cysteine (NAC) pretreatment did not satisfactorily alleviate the UPR in cells exposed to PFOA even though the increase of ROS was less evident. Furthermore, exposure of HepG2 cells to PFOA in the presence of sodium 4-phenylbutyrate (4-PBA), a chemical chaperone and ER stress inhibitor, suggested that 4-PBA alleviated the UPR and autophagosome accumulation induced by PFOA in cells. In addition, several toxicological effects attributed to PFOA exposure, including cell cycle arrest, proteolytic activity impairment, and neutral lipid accumulation, were also improved by 4-PBA cotreatment in cells. In vivo study demonstrated that PFOA induced lipid metabolism perturbation and liver injury were partially ameliorated by 4-PBA in mice after 28 days of exposure. These findings demonstrated that PFOA induced ER stress leading to UPR might play an important role in PFOA-induced hepatotoxic effects, and chemical chaperone 4-PBA could ameliorate the effects. PMID- 26159509 TI - The effect of treadmill training and N-acetyl-l-cysteine intervention on biogenesis of cytochrome c oxidase (COX). AB - Mitochondrial biogenesis refers to increased content of mitochondria, which has been shown to be promoted by aerobic exercise. During this process, oxidative stress is considered the essential initiator. Even though some studies have addressed the issue as to whether antioxidants would hamper the effects of exercise on mitochondrial biogenesis, no consensus has been achieved. Therefore, the purpose of the present study was to investigate the effects of exercise and antioxidant intervention on mitochondrial biogenesis, as well as COX biogenesis. Thirty-two clean-grade male ICR mice were randomly assigned to a control group (Con), exercise group (Ex), N-acetyl-l-cysteine group (NAC), or NAC plus exercise group (NEx). The NAC and NEx groups were injected with NAC (0.1 mg/g/2 days) intraperitoneally for 3 weeks, whereas the Con and Ex groups were administered saline for the same period of time. Mice assigned to Ex and NEx groups started exercise training 1 week before drug intervention was initiated. After 1 week of acclimatization, the mice were allowed to run at a speed of 28 m/min for 60 min, 6 days a week. The results showed that exercise training caused an increase in mRNA and protein levels of COXIV, whereas NAC intervention lowered the two so significantly that even exercise training could not reverse the effect of NAC intervention. Our data suggest that even though antioxidant intervention could alleviate oxidative damage caused by exercise, it was not necessarily beneficial for mitochondrial biogenesis. PMID- 26159508 TI - Pyridoxamine protects proteins from damage by hypohalous acids in vitro and in vivo. AB - Diabetes is characterized, in part, by activation of toxic oxidative and glycoxidative pathways that are triggered by persistent hyperglycemia and contribute to diabetic complications. Inhibition of these pathways may benefit diabetic patients by delaying the onset of complications. One such inhibitor, pyridoxamine (PM), had shown promise in clinical trials. However, the mechanism of PM action in vivo is not well understood. We have previously reported that hypohalous acids can cause disruption of the structure and function of renal collagen IV in experimental diabetes (K.L. Brown et al., Diabetes 64:2242-2253, 2015). In the present study, we demonstrate that PM can protect protein functionality from hypochlorous and hypobromous acid-derived damage via a rapid direct reaction with and detoxification of these hypohalous acids. We further demonstrate that PM treatment can ameliorate specific hypohalous acid-derived structural and functional damage to the renal collagen IV network in a diabetic animal model. These findings suggest a new mechanism of PM action in diabetes, namely sequestration of hypohalous acids, which may contribute to known therapeutic effects of PM in human diabetic nephropathy. PMID- 26159510 TI - Residual lymph node status is an independent prognostic factor in esophageal squamous cell Carcinoma with pathologic T0 after preoperative radiotherapy. AB - OBJECTIVE: To evaluate the prognostic factors affecting survival in esophageal squamous cell Carcinoma (ESCC) patients with pathologic T0 (ypT0) underwent preoperative radiotherapy. PATIENTS AND METHODS: Two hundred and ninety-six patients with ESCC who had received preoperative radiotherapy from 1980 to 2007 were retrospectively analyzed. One hundred patients were ypT0 after preoperative radiotherapy. Univariate and multivariate analyses were performed to evaluate the predictive impact of residual lymph node status on overall survival (OS) and progression-free survival (PFS). RESULTS: Among the originally analyzed 296 patients, 100 (33.7 %) patients had ypT0, including 78 patients (78 %) with ypT0N0, and 22 patients (22 %) with ypT0N1. The 5-year OS of the total patients was 42.4 %. Patients with ypT0N0 have significant improved 5-year OS and PFS than ypT0N1 patients (OS: 50.7 % vs 13.6 %, P = 0.004; PFS: 49.6 % vs 13.6 %, P = 0.003). In multivariate analysis, residual lymph node status was also an independent prognostic factors for OS (HR: 0.406, 95 % CI: 0.240-0.686, P = 0.001) and PFS (HR: 0.427, 95 % CI: 0.248-0.734, P = 0.002). CONCLUSION: Our results indicate that patients with ypT0N0 after preoperative radiotherapy had significantly better OS and PFS than patients with ypT0N1 in ESCC. Residual nodal metastasis of ESCC patients with pathological complete response of the primary tumor after neoadjuvant radiotherapy does influence prognosis. PMID- 26159511 TI - The importin alpha subunit PsIMPA1 mediates the oxidative stress response and is required for the pathogenicity of Phytophthora sojae. AB - The sensing of extracellular signals and their transduction into an appropriate response are crucial for the survival and virulence of plant pathogens. Eukaryotic plant pathogens must overcome the obstacles posed by nuclear membranes to manipulate gene expression to adapt to the host challenge. A highly sophisticated mechanism is the use of importins to transport proteins into the nucleus. In this study, we identified a conserved importin alpha gene, PsIMPA1, in Phytophthora sojae that was differentially expressed during the life cycle of this soybean pathogen. PsIMPA1 expression was lowest in zoospores and cysts but relatively consistent during the other life cycle stages, except for a slight increase at 6h post infection. Silenced mutants Psimpa1 had a decreased growth rate, an aberrant mycelial morphology, and a severely impaired ability to form oospores and sporangia. In addition, the Psimpa1 mutants exhibited reduced pathogenicity compared to the wild type. 3,3-Diaminobenzidine (DAB) staining and in vitro hydrogen peroxide tolerance assays showed that the scavenging of reactive oxygen species by these mutants was significantly impaired. Taken together, these results indicate that PsIMPA1 regulates multiple processes during the life cycle of P. sojae. PMID- 26159512 TI - Alveolar rhabdomyosarcoma of the anterior mediastinum with vessel invasion in a 4 month-old boy: a case report. AB - INTRODUCTION: Alveolar rhabdomyosarcomas of the mediastinum in children are rarely reported. Multimodality therapy including chemotherapy, surgery and radiotherapy make up the backbone of the treatment of childhood rhabdomyosarcomas. Complete resection whenever achievable is an important prognostic factor. However, complete resection of tumors in the mediastinum often poses a unique challenge to thoracic surgeons due to their close proximity to important neurovascular structures. Complete resection may not always be possible and judicious peri-operative planning and preparation are required to avoid creating unnecessary surgical morbidities resulting in delay of adjuvant therapy. CASE PRESENTATION: A 4-month-old Chinese baby boy was presented to our hospital with stridor, shortness of breath and episodes of cyanosis. Imaging studies found an anterior mediastinal mass compressing the trachea and other neurovascular structures and he was diagnosed to have alveolar rhabdomyosarcoma. Our patient received upfront chemotherapy and subsequently open resection of the mass was attempted via median sternotomy. Intraoperatively, the mass had invaded into the great vessels, precluding a complete resection. Debulking surgery was performed instead and our patient received timely postoperative chemoradiotherapy. CONCLUSIONS: We report a rare case of childhood alveolar rhabdomyosarcoma of the mediastinum with vascular invasion treated with chemoradiotherapy and debulking surgery. Complete resection was not possible due to the close proximity to the great vessels. Different surgical approaches to the mediastinum have been reported in adults and children alike. Regardless of the surgical access, the treatment of childhood rhabdomyosarcomas should be individualized, with careful balance between surgical clearance and surgical morbidity. PMID- 26159514 TI - Enlargement of the Internal Auditory Canal and Associated Posterior Fossa Anomalies in PHACES Association. AB - We noted enlargement of the internal auditory canal in several of our patients with posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, and sternal or supraumbilical defects (PHACES) association and hence evaluated children with PHACES for the presence of an enlarged internal auditory canal and potential associated findings, including infantile hemangioma within the internal auditory canal, to understand the genesis of this enlargement. We reviewed our records to identify children with PHACES association who had been evaluated with MR imaging at our institutions. Imaging was reviewed for abnormal enhancement in the internal auditory canal, internal auditory canal enlargement, cerebellar hypoplasia, prominence of the petrous ridge, and deformity of the calvarium. We raise the possibility of an association between enlargement of the internal auditory canal in PHACES and a generalized malformation of the posterior fossa with cerebellar and calvarial hypoplasia. PMID- 26159513 TI - Mobile element insertions are frequent in oesophageal adenocarcinomas and can mislead paired-end sequencing analysis. AB - BACKGROUND: Mobile elements are active in the human genome, both in the germline and cancers, where they can mutate driver genes. RESULTS: While analysing whole genome paired-end sequencing of oesophageal adenocarcinomas to find genomic rearrangements, we identified three ways in which new mobile element insertions appear in the data, resembling translocation or insertion junctions: inserts where unique sequence has been transduced by an L1 (Long interspersed element 1) mobile element; novel inserts that are confidently, but often incorrectly, mapped by alignment software to L1s or polyA tracts in the reference sequence; and a combination of these two ways, where different sequences within one insert are mapped to different loci. We identified nine unique sequences that were transduced by neighbouring L1s, both L1s in the reference genome and L1s not present in the reference. Many of the resulting inserts were small fragments that include little or no recognisable mobile element sequence. We found 6 loci in the reference genome to which sequence reads from inserts were frequently mapped, probably erroneously, by alignment software: these were either L1 sequence or particularly long polyA runs. Inserts identified from such apparent rearrangement junctions averaged 16 inserts/tumour, range 0-153 insertions in 43 tumours. However, many inserts would not be detected by mapping the sequences to the reference genome, because they do not include sufficient mappable sequence. To estimate total somatic inserts we searched for polyA sequences that were not present in the matched normal or other normals from the same tumour batch, and were not associated with known polymorphisms. Samples of these candidate inserts were verified by sequencing across them or manual inspection of surrounding reads: at least 85 % were somatic and resembled L1-mediated events, most including L1Hs sequence. Approximately 100 such inserts were detected per tumour on average (range zero to approximately 700). CONCLUSIONS: Somatic mobile elements insertions are abundant in these tumours, with over 75 % of cases having a number of novel inserts detected. The inserts create a variety of problems for the interpretation of paired-end sequencing data. PMID- 26159515 TI - Histologic Analysis of Retrieved Clots in Acute Ischemic Stroke: Correlation with Stroke Etiology and Gradient-Echo MRI. AB - BACKGROUND AND PURPOSE: It is unclear whether clot composition analysis is helpful to predict a stroke mechanism in acute large vessel occlusion. In addition, the relationship between early vessel signs on imaging studies and clot compositions has been poorly understood. The purpose of this study was to elucidate the relationship between clot composition and stroke etiology following mechanical thrombectomy and to investigate the effect of varied clot compositions on gradient-echo MR imaging of clots. MATERIALS AND METHODS: Histopathologic analysis of retrieved clots from 37 patients with acute MCA occlusion was performed. Patients underwent gradient-echo imaging before endovascular therapy. Retrieved clots underwent semiquantitative proportion analysis to quantify red blood cells, fibrin, platelets, and white blood cells by area. Correlations between clot compositions and stroke subtypes and susceptibility vessel signs on gradient-echo imaging were assessed. RESULTS: Stroke etiology was classified as cardioembolism in 22 patients (59.4%), large-artery atherosclerosis in 8 (21.6%), and undetermined in 7 (18.9%). The clots from cardioembolism had a significantly higher proportion of red blood cells (37.8% versus 16.9%, P = .031) and a lower proportion of fibrin (32.3% versus 48.5%, P = .044) compared with those from large-artery atherosclerosis. The proportion of red blood cells was significantly higher in clots with a susceptibility vessel sign than in those without it (48.0% versus 1.9%, P < .001), whereas the proportions of fibrin (26.4% versus 57.0%, P < .001) and platelets (22.6% versus 36.9%, P = .011) were significantly higher in clots without a susceptibility vessel sign than those with it. CONCLUSIONS: The histologic composition of clots retrieved from cerebral arteries in patients with acute stroke differs between those with cardioembolism and large-artery atherosclerosis. In addition, a susceptibility vessel sign on gradient-echo imaging is strongly associated with a high proportion of red blood cells and a low proportion of fibrin and platelets in retrieved clots. PMID- 26159516 TI - Single-Layer WEBs: Intrasaccular Flow Disrupters for Aneurysm Treatment Feasibility Results from a European Study. AB - BACKGROUND AND PURPOSE: The safety and efficiency of the dual-layer Woven EndoBridge (WEB) device has already been published. However, this international multicenter study sought to evaluate the safety of single-layer devices, which are the newest generation of the WEB intrasaccular flow-disrupter family. They have been designed to offer smaller-sized devices with a lower profile to optimize navigability and delivery, which may, in turn, broaden their range of use. MATERIALS AND METHODS: Data from all consecutive patients treated with a single-layer WEB device, in 10 European centers from June 2013 to May 2014 were included. Clinical presentations, technical details, intra- and perioperative complications, and outcomes at discharge were recorded. Clinical and angiographic data at last follow-up were also analyzed when available. RESULTS: Ninety patients with 98 WEB-treated aneurysms were included in this study. In 93 cases (95%), WEB placement was possible. Complete occlusion at the end of the procedure was obtained in 26 instances (26%). Additional treatment during the procedure (coiling and/or stent placement) was necessary in 12 cases (12.7%). Procedure related complications occurred in 13 cases, leading to permanent neurologic deficits in 4 patients (4.4%). Early vascular imaging follow-up data were available for 44 patients (57%), with an average time interval of 3.3 months. Treatment-related morbidity and mortality rates at last follow-up were 2.2% and 1.1%, respectively. CONCLUSIONS: In this study, the feasibility and safety of the single-layer WEB device was comparable with that of the double-layer. However, further studies are needed to evaluate long-term efficacies. PMID- 26159517 TI - Subspecialty Virtual Impact Factors within a Dedicated Neuroimaging Journal. AB - BACKGROUND AND PURPOSE: The growing number of subspecialties within neuroradiology compete for pages in neuroradiology journals. We performed a bibliometric analysis of the American Journal of Neuroradiology to identify the virtual Impact Factor of different journal subsections and article topics. MATERIALS AND METHODS: Original Research and Review Articles published in American Journal of Neuroradiology during 2010-2012 were evaluated. The journal section for each article was recorded, and the number of citations was evaluated by using the Web of Science database. Numbers of citations within the first 2 years after publication were evaluated, normalized to the 2013 journal Impact Factor (for American Journal of Neuroradiology, 3.675), and used to calculate a virtual Impact Factor for different journal subsections. RESULTS: One thousand forty-nine Original Research and Review Articles were published during this time, which obtained an average of 6.59 citations each within their first 2 years after publication; 91.8% of articles obtained at least 1 citation. Expedited Publications had the greatest number of citations, averaging 43.7 citations each (virtual Impact Factor, 24.39), followed by Review Articles averaging 9.39 citations each (virtual Impact Factor 5.23). Virtual Impact Factors for other sections were the following: Interventional, 4.54; Brain, 3.70; Pediatrics, 2.91; Functional, 2.74; Head & Neck, 2.24; and Spine, 1.86. Virtual Impact Factors for article topics were the following: interventional, 4.75; functional/advanced, 3.79; brain, 3.66; pediatrics, 2.99; head and neck, 2.46; and spine, 2.32. CONCLUSIONS: Citation patterns of Original Research and Review Articles in American Journal of Neuroradiology varied widely on the basis of subsections. Understanding the citation patterns of specific topics and subsections of a journal may aid authors and editors in evaluating the appropriate balance among various topics and allow authors to determine whether their articles are being cited at a level expected for similar ones in a journal. PMID- 26159518 TI - Assessing the Efficacy of Mdm2/Mdm4-Inhibiting Stapled Peptides Using Cellular Thermal Shift Assays. AB - Previous publications on stapled peptide inhibitors against Mdm2/Mdm4-p53 interactions have established that this new class of drugs have the potential to be easily optimised to attain high binding affinity and specificity, but the mechanisms controlling their cellular uptake and target engagement remain elusive and controversial. To aid in understanding the rules of peptide and staple design, and to enable rapid optimisation, we employed the newly-developed cellular thermal shift assay (CETSA). CETSA was able to validate stapled peptide binding to Mdm2 and Mdm4, and the method was also used to determine the extent of cellular uptake, cellular availability, and intracellular binding of the endogenous target proteins in its native environment. Our data suggest that while the stapled peptides engage their targets intracellularly, more work is needed to improve their cellular entry and target engagement efficiency in vivo. CETSA now provides a valuable tool to optimize such in vivo properties of stapled peptides. PMID- 26159520 TI - Draft Genome Sequence of a Highly Virulent Rabbit Staphylococcus aureus Strain. AB - We report the draft genome sequence of Staphylococcus aureus Sp17, a typical highly virulent (HV) rabbit strain. As current medicine apparently fails to effectively reduce disease and economical losses caused by this organism, it is essential to gain better insight on its genomic arrangement. PMID- 26159521 TI - Complete Genome Sequences of Serotype O Foot-and-Mouth Disease Viruses Recovered from Experimental Persistently Infected Cattle. AB - For the first time, the complete genome sequences of the six serotype O foot-and mouth disease viruses from persistently infected carrier cattle are reported here. No consistent amino acid changes were found in these viruses obtained from persistently infected cattle compared with the complete genome of the parent virus that was used to infect the cattle. PMID- 26159519 TI - Acquired genetic alterations in tumor cells dictate the development of high-risk neuroblastoma and clinical outcomes. AB - BACKGROUND: Determining the driving factors and molecular flow-through that define the switch from favorable to aggressive high-risk disease is critical to the betterment of neuroblastoma cure. METHODS: In this study, we examined the cytogenetic and tumorigenic physiognomies of distinct population of metastatic site- derived aggressive cells (MSDACs) from high-risk tumors, and showed the influence of acquired genetic rearrangements on poor patient outcomes. RESULTS: Karyotyping in SH-SY5Y and MSDACs revealed trisomy of 1q, with additional non random chromosomal rearrangements on 1q32, 8p23, 9q34, 15q24, 22q13 (additions), and 7q32 (deletion). Array CGH analysis of individual clones of MSDACs revealed genetic alterations in chromosomes 1, 7, 8, and 22, corresponding to a gain in the copy numbers of LOC100288142, CD1C, CFHR3, FOXP2, MDFIC, RALYL, CSMD3, SAMD12 AS1, and MAL2, and a loss in ADAM5, LOC400927, APOBEC3B, RPL3, MGAT3, SLC25A17, EP300, L3MBTL2, SERHL, POLDIP3, A4GALT, and TTLL1. QPCR analysis and immunoblotting showed a definite association between DNA-copy number changes and matching transcriptional/translational expression in clones of MSDACs. Further, MSDACs exert a stem-like phenotype. Under serum-free conditions, MSDACs demonstrated profound tumorosphere formation ex vivo. Moreover, MSDACs exhibited high tumorigenic capacity in vivo and prompted aggressive metastatic disease. Tissue microarray analysis coupled with automated IHC revealed significant association of RALYL to the tumor grade in a cohort of 25 neuroblastoma patients. Clinical outcome association analysis showed a strong correlation between the expression of CFHR3, CSMD3, MDFIC, FOXP2, RALYL, POLDIP3, SLC25A17, SERHL, MGAT3, TTLL1, or LOC400927 and overall and relapse-free survival in patients with neuroblastoma. CONCLUSION: Together, these data highlight the ongoing acquired genetic rearrangements in undifferentiated tumor-forming neural crest cells, and suggest that these alterations could switch favorable neuroblastoma to high-risk aggressive disease, promoting poor clinical outcomes. PMID- 26159522 TI - Draft Genome Sequence of a Natural Root Isolate, Bacillus subtilis UD1022, a Potential Plant Growth-Promoting Biocontrol Agent. AB - Bacillus subtilis, which belongs to the phylum Firmicutes, is the most widely studied Gram-positive model organism. It is found in a wide variety of environments and is particularly abundant in soils and in the gastrointestinal tracts of ruminants and humans. Here, we present the complete genome sequence of the newly described B. subtilis strain UD1022. The UD1022 genome consists of a 4.025-Mbp chromosome, and other major findings from our analysis will provide insights into the genomic basis of it being a plant growth-promoting rhizobacterium (PGPR) with biocontrol potential. PMID- 26159523 TI - Draft Genome Sequence of Microvirga vignae Strain BR 3299T, a Novel Symbiotic Nitrogen-Fixing Alphaproteobacterium Isolated from a Brazilian Semiarid Region. AB - Microvirga vignae is a recently described species of root-nodule bacteria isolated from cowpeas grown in a Brazilian semiarid region. We report here the 6.4-Mb draft genome sequence and annotation of M. vignae type strain BR 3299. This genome information may help to understand the mechanisms underlying the ability of the organism to grow under drought and high-temperatures conditions. PMID- 26159524 TI - Complete Genome Sequence of a Novel Porcine Reproductive and Respiratory Syndrome Virus That Emerged in China. AB - A novel porcine reproductive and respiratory syndrome virus (PRRSV) strain with 393 nucleotide deletions in the nonstructural protein 2 (Nsp2) region was examined in this study. Results will help improve our understanding of the epidemiology and genetic diversity of the North American-type PRRSV in China. PMID- 26159525 TI - Complete Genome Sequence of Tomato Mosaic Virus Isolated from Jasmine in the United States. AB - Tomato mosaic virus was reported from jasmine in Florida. We present the first complete genome sequence of a tomato mosaic virus isolate from this woody perennial plant in the United States. PMID- 26159526 TI - Draft Genome Sequence of Streptomyces incarnatus NRRL8089, which Produces the Nucleoside Antibiotic Sinefungin. AB - A draft genome sequence of Streptomyces incarnatus NRRL8089, which produces the nucleoside antibiotic sinefungin, is described here. The genome contains 8,897,465 bp in 76 contigs and 8,266 predicted genes. Interestingly, the genome encodes an open reading frame for selenocysteine-containing formate dehydrogenase O and the selenoprotein biosynthetic gene cluster selABCD. PMID- 26159527 TI - Metagenomic Assembly and Draft Genome Sequence of an Uncharacterized Prevotella sp. from Nelore Rumen. AB - Prevotella is one of the most abundant genera in bovine rumen, although no genome has yet been assembled by a metagenomics approach applied to Brazilian Nelore. We report the draft genome sequence of Prevotella sp., comprising 2,971,040 bp, obtained using the Illumina sequencing platform. This genome includes 127 contigs and presents a low 48% GC. PMID- 26159528 TI - Complete Genome Sequence of Pragia fontium 24613, an Environmental Bacterium from the Family Enterobacteriaceae. AB - The complete genome sequence of Pragia fontium 24613 was determined using PacBio RSII, Roche 454, and SOLiD sequencing. A total of 3,579 genes were predicted, including 3,338 protein-coding sequences and 146 pseudogenes. This is the first whole-genome sequence of a strain belonging to the environmental genera of the family Enterobacteriaceae. PMID- 26159529 TI - Complete Genome Sequence of a CTX-M-15-Producing Klebsiella pneumoniae Outbreak Strain from Multilocus Sequence Type 514. AB - We report here the genome sequence of a multidrug-resistant Klebsiella pneumoniae strain, which caused an outbreak in a neonatal ward in 2011. The genome consists of a single chromosome (5,278 kb) and three plasmids (362 kb, 5 kb, and 4 kb). PMID- 26159530 TI - Genome Sequence of Vibrio VPAP30, Isolated from an Episode of Massive Mortality of Reared Larvae of the Scallop Argopecten purpuratus. AB - We report here the 5.167-Mbp draft genome sequence of Vibrio VPAP30, isolated from an Argopecten purpuratus larval culture. Vibrio VPAP30 is the etiological agent of a vibriosis outbreak causing a complete collapse of a larval culture of the scallop A. purpuratus, which occurred in a commercial hatchery in Chile. PMID- 26159531 TI - Draft Whole-Genome Sequence of Serratia sp. Strain TEL, Associated with Oscheius sp. TEL-2014 (Nematoda: Rhabditidae) Isolated from a Grassland in South Africa. AB - Here, we report on the draft genome sequence of Serratia sp. strain TEL, associated with Oscheius sp. TEL-2014 (Nematoda: Rhabditidae, KM492926) isolated from a grassland in Suikerbosrand Nature Reserve near Johannesburg in South Africa. Serratia sp. strain TEL has a genome size of 5,000,541 bp with 4,647 genes and a G+C content of 59.1%. PMID- 26159532 TI - Genome Sequence of Arthrobacter sp. YC-RL1, an Aromatic Compound-Degrading Bacterium. AB - We report the 4.04-Mb draft genome sequence of Arthrobacter sp. YC-RL1, an aromatic compound-degrading bacterium. YC-RL1 could degrade a wide range of aromatic compounds, including naphthaline, 1,2,3,4-tetrachlorobenzene, fluorene, 4-nitrophenol, bisphenol A, biphenyl, and p-xylene. The genome sequence of YC-RL1 will promote the investigation of the biodegradation of aromatic compounds. PMID- 26159533 TI - Full-Genome Sequence of a Novel Varicella-Zoster Virus Clade Isolated in Mexico. AB - Varicella-zoster virus (VZV) is a member of the Herpesviridae family, which causes varicella (chicken pox) and herpes zoster (shingles) in humans. Here, we report the complete genome sequence of varicella-zoster virus, isolated from a vesicular fluid sample, revealing the circulation of VZV clade VIII in Mexico. PMID- 26159534 TI - Whole-Genome Sequences of Multidrug-Resistant Escherichia coli Strains Sharing the Same Sequence Type (ST410) and Isolated from Human and Avian Sources in Italy. AB - Extraintestinal pathogenic Escherichia coli (ExPEC) is involved in a wide spectrum of human diseases. Chickens have been suggested as reservoirs for fluoroquinolone (FQ)-resistant ExPEC strains. Here, we report the whole-genome sequences of 4 E. coli strains sharing the same sequence type (ST) (ST410) and that were isolated from human and avian sources in Italy. PMID- 26159535 TI - Draft Genome Sequence of the Carbofuran-Mineralizing Novosphingobium sp. Strain KN65.2. AB - Complete mineralization of the N-methylcarbamate insecticide carbofuran, including mineralization of the aromatic moiety, appears to be confined to sphingomonad isolates. Here, we report the first draft genome sequence of such a sphingomonad strain, i.e., Novosphingobium sp. KN65.2, isolated from carbofuran exposed agricultural soil in Vietnam. PMID- 26159536 TI - Draft Genome Sequences of the Two Unrelated Macrolide-Resistant Corynebacterium argentoratense Strains CNM 463/05 and CNM 601/08, Isolated from Patients in the University Hospital of Leon, Spain. AB - Corynebacterium argentoratense has been associated mainly with infections in the human respiratory tract. Genome sequencing of two unrelated clinical macrolide resistant strains, CNM 463/05 and CNM 601/08, revealed the presence of the antibiotic resistance gene erm(X) allocated to a specific genomic region with 100% similarity to the widely distributed transposable element Tn5432. PMID- 26159537 TI - Draft Genome Sequence of Clavibacter michiganensis subsp. nebraskensis Strain DOAB 397, Isolated from an Infected Field Corn Plant in Manitoba, Canada. AB - In 2014, the pathogen Clavibacter michiganensis subsp. nebraskensis was isolated from symptomatic corn leaves in Manitoba, Canada. We report the draft genome sequence of C. michiganensis subsp. nebraskensis DOAB 397, consisting of 3.059 Mb with 73.0% G+C content, 2,922 predicted protein-coding sequences, 45 tRNAs, 3 rRNAs, and 37 pseudogenes. PMID- 26159538 TI - Complete Genome Sequence of Mycoplasma hominis Strain Sprott (ATCC 33131), Isolated from a Patient with Nongonococcal Urethritis. AB - Presented here is the complete and annotated genome sequence of Mycoplasma hominis Sprott (ATCC 33131). The chromosome comprises 695,214 bp, which is approximately 30 kb larger than the syntenic genome of M. hominis PG21(T). Tetracycline resistance of strain Sprott is most probably conferred by the tetM determinant, harbored on a mosaic transposon-like structure. PMID- 26159539 TI - The percentage of lepidic growth is an independent prognostic factor in invasive adenocarcinoma of the lung. AB - BACKGROUND: The literature is inconclusive as to whether the percentage of the lepidic component of an invasive adenocarcinoma (AC) of the lung influences prognosis. We studied a population-based series of selected, resected invasive pulmonary ACs to determine if incremental increases in the lepidic component were an independent, prognostic variable. METHODS: Patients undergoing resection for lung cancer reported to the Cancer Registry of Norway and diagnosed in the period 1993-2002 with a bronchioloalveolar carcinoma (BAC) (old terminology) (adenocarcinoma in situ, AIS in the new terminology) in the lung were selected. A pulmonary pathologist reviewed all sections and estimated the percentage of the lepidic component. Follow-up of survival was to the end of 2013. RESULTS: One hundred thirty-one patients were identified, 102 had AC with lepidic growth. Of these, 44 had AC with a component of lepidic growth less than 50% and seven had AC with 95% lepidic component or more. One of the latter cases was considered to be AIS. In regression analyses, superior survival was associated with a greater lepidic component (p = 0.041). Mucinous tumors had a worse prognosis than non mucinous (p = 0.012) in regression analyses, as did increasing age and stage. The five-year observed survival was 69.0% for non-mucinous cases and 66.7% for the group with a lepidic component of 80% or greater. CONCLUSION: The percentage of the lepidic component appears to be an independent, significant prognostic factor in a selection of pulmonary AC. PMID- 26159540 TI - Remission of proteinuria indicates good prognosis in patients with diffuse proliferative lupus nephritis. AB - Proteinuria is a well-known risk factor for the progression of renal dysfunction in chronic kidney disease; however, its importance for estimating the prognosis of lupus nephritis requires verification. Korean adult patients with renal biopsy diagnosed diffuse proliferative lupus nephritis who had undergone three or more consecutive urine protein to creatinine ratio or urine dipstick tests within six months after renal biopsy were enrolled. The cumulative risks, predictors, and outcomes of proteinuric remission and flare were evaluated. This study included 26 men and 167 women with a mean age at renal biopsy of 31.2 +/- 9.8 years. Eighty-two (42.5%) patients experienced proteinuric remission during the follow up period. During a mean follow-up of 157.9 +/- 69.5 months, among patients who achieved proteinuric remission, one died, one developed end-stage renal disease (ESRD), and two had composite outcomes; among patients without remission, nine died, 24 developed ESRD, and 30 had composite outcomes. Patients who achieved proteinuric remission had a 0.089-fold risk (95% CI: 0.011-0.736) of mortality, 0.110-fold risk (95% CI: 0.013-0.904) of incident ESRD, and 0.210-fold risk (95% CI: 0.048-0.920) of a composite outcome compared to patients without remission. Among the 82 patients who achieved proteinuric remission, 59 (72.0%) experienced at least one proteinuria flare; however, relapse did not correlate with the incidence of outcomes. In conclusion, proteinuric remission is an independent predictive prognostic marker of good renal survival and mortality, regardless of the interval from biopsy to remission, recurrence of proteinuria after remission, renal function status at remission, or hematuria remission. PMID- 26159542 TI - Saluting our leaders. PMID- 26159541 TI - Within- and between-group regression for improving the robustness of causal claims in cross-sectional analysis. AB - BACKGROUND: A major objective of environmental epidemiology is to elucidate exposure-health outcome associations. To increase the variance of observed exposure concentrations, researchers recruit individuals from different geographic areas. The common analytical approach uses multilevel analysis to estimate individual-level associations adjusted for individual and area covariates. However, in cross-sectional data this approach does not differentiate between residual confounding at the individual level and at the area level. An approach allowing researchers to distinguish between within-group effects and between-group effects would improve the robustness of causal claims. METHODS: We applied an extended multilevel approach to a large cross-sectional study aimed to elucidate the hypothesized link between drinking water pollution from perfluoroctanoic acid (PFOA) and plasma levels of C-reactive protein (CRP) or lymphocyte counts. Using within- and between-group regression of the individual PFOA serum concentrations, we partitioned the total effect into a within- and between-group effect by including the aggregated group average of the individual exposure concentrations as an additional predictor variable. RESULTS: For both biomarkers, we observed a strong overall association with PFOA blood levels. However, for lymphocyte counts the extended multilevel approach revealed the absence of a between-group effect, suggesting that most of the observed total effect was due to individual level confounding. In contrast, for CRP we found consistent between- and within-group effects, which corroborates the causal claim for the association between PFOA blood levels and CRP. CONCLUSION: Between- and within-group regression modelling augments cross-sectional analysis of epidemiological data by supporting the unmasking of non-causal associations arising from hidden confounding at different levels. In the application example presented in this paper, the approach suggested individual confounding as a probable explanation for the first observed association and strengthened the robustness of the causal claim for the second one. PMID- 26159544 TI - European Union ERASMUS+ Program and the Jean Monnet Activities. PMID- 26159543 TI - Suppression of beta3-integrin in mice triggers a neuropilin-1-dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis. AB - Anti-angiogenic treatments against alphavbeta3-integrin fail to block tumour growth in the long term, which suggests that the tumour vasculature escapes from angiogenesis inhibition through alphavbeta3-integrin-independent mechanisms. Here, we show that suppression of beta3-integrin in mice leads to the activation of a neuropilin-1 (NRP1)-dependent cell migration pathway in endothelial cells via a mechanism that depends on NRP1's mobilisation away from mature focal adhesions following VEGF-stimulation. The simultaneous genetic targeting of both molecules significantly impairs paxillin-1 activation and focal adhesion remodelling in endothelial cells, and therefore inhibits tumour angiogenesis and the growth of already established tumours. These findings provide a firm foundation for testing drugs against these molecules in combination to treat patients with advanced cancers. PMID- 26159545 TI - Expression of Programmed Death 1 Ligand in Different Compartments of Chronic Lymphocytic Leukemia. AB - BACKGROUND: The programmed death 1 (PD-1) receptor pathway is responsible for the negative regulation of both T and B lymphocytes upon activation of these cells. There is growing evidence that chronic lymphocytic leukemia (CLL) cells exploit the PD-1 ligand (PD-L1) to resist antitumor immune reactions and maintain their survival by shaping their own microenvironment. METHODS: We used a quantitative RT-PCR method to analyze PD-L1 gene expression in bone marrow and peripheral blood mononuclear cells, representing the proliferation and accumulation compartments of CLL. RESULTS: PD-L1 expression was found to be significantly higher in 112 CLL patients than in controls. Levels of PD-L1 expression in bone marrow and peripheral blood were comparable and showed a positive correlation. Furthermore, expression of PDL1 strongly correlated with expression of PD-1 receptor in mononuclear cells from the same compartment, and was not affected by incubation with immunomodulatory drug thalidomide. CONCLUSION: PD-L1 expression is shared between CLL cells localized in distinct disease compartments, demonstrating that PD-1/PD-L1 a universal target for therapy. PMID- 26159546 TI - Cellphone-Based Hand-Held Microplate Reader for Point-of-Care Testing of Enzyme Linked Immunosorbent Assays. AB - Standard microplate based enzyme-linked immunosorbent assays (ELISA) are widely utilized for various nanomedicine, molecular sensing, and disease screening applications, and this multiwell plate batched analysis dramatically reduces diagnosis costs per patient compared to nonbatched or nonstandard tests. However, their use in resource-limited and field-settings is inhibited by the necessity for relatively large and expensive readout instruments. To mitigate this problem, we created a hand-held and cost-effective cellphone-based colorimetric microplate reader, which uses a 3D-printed opto-mechanical attachment to hold and illuminate a 96-well plate using a light-emitting-diode (LED) array. This LED light is transmitted through each well, and is then collected via 96 individual optical fibers. Captured images of this fiber-bundle are transmitted to our servers through a custom-designed app for processing using a machine learning algorithm, yielding diagnostic results, which are delivered to the user within ~1 min per 96 well plate, and are visualized using the same app. We successfully tested this mobile platform in a clinical microbiology laboratory using FDA-approved mumps IgG, measles IgG, and herpes simplex virus IgG (HSV-1 and HSV-2) ELISA tests using a total of 567 and 571 patient samples for training and blind testing, respectively, and achieved an accuracy of 99.6%, 98.6%, 99.4%, and 99.4% for mumps, measles, HSV-1, and HSV-2 tests, respectively. This cost-effective and hand-held platform could assist health-care professionals to perform high throughput disease screening or tracking of vaccination campaigns at the point-of care, even in resource-poor and field-settings. Also, its intrinsic wireless connectivity can serve epidemiological studies, generating spatiotemporal maps of disease prevalence and immunity. PMID- 26159547 TI - Effect of temperature on embryonic development of Melanotaenia boesemani (Allen and Cross, 1982). AB - The present study aimed to provide data on the time required for Melanotaenia boesemani to complete embryonic development, and to investigate the influence that incubation at different temperatures caused in this species. The effects of temperature on the time and hatching rate are presented, as well as information related to embryonic development stages. After fertilization, the eggs were kept in incubators at 23, 26, 29 or 32 degrees C and observed at predetermined times until the moment of hatching. Stages of development were identified and classified according to morphological and physiological characteristics. Oil droplets were visualized inside the eggs as well as filament adhesion present at the chorion. Embryonic development was similar to that observed in other species of the genus Melanotaenia with hatching and faster development in higher temperatures. PMID- 26159548 TI - Injury to hypopharynx by a foreign body with subsequent candida osteomyelitis of the upper cervical spine. PMID- 26159549 TI - Mobile lumbar spine ependymoma: case report and review of literature. AB - Migrating intra-spinal lesions are quite rare, and are most of the reported cases are schwannomas. Several theories have been proposed to explain the changing location of an intra-spinal tumor. We present a very rare case of migrating lumbar intra-spinal intra-dural lesion at the conus level, the pathology of which was an ependymoma, and review the possible etiologies of such a unique occurrence in view of the reported literature. We hypothesize loose connection to the tissue of origin, likely the filum, as the cause in our case. We thus highlight the importance of repeated imaging and careful planning before surgical intervention of intra-spinal intra-dural lesions, to avoid complications and wrong level surgery, especially when the lesions are in the cauda-equina area. PMID- 26159550 TI - Advantages and disadvantages of intraoperative language tasks in awake surgery: a three-task approach for prefrontal tumors. AB - Multidisciplinary efforts are being made to provide surgical teams with sensitive and specific tasks for language mapping in awake surgery. Researchers and clinicians have elaborated different tasks over time. A fair amount of work has been directed to study the neurofunctional correlates of some of these tasks, and there is recent interest in their standardization. However, little discussion exists on the advantages and disadvantages that each task poses from the perspective of the cognitive neuroscience of language. Such an approach may be a relevant step to assess task validity, to avoid using tasks that tap onto similar processes, and to provide patients with a surgical treatment that ensures maximal tumor resection while avoiding postoperative language deficits. An understanding of the language components that each task entails may also be relevant to improve the current assessments and the ways in which tasks are administered, and to disentangle neurofunctional questions. We reviewed 17 language mapping tasks that have been used in awake surgery. Overt production tasks have been a preferred choice over comprehension tasks. Tasks tapping lexico-semantic processes, particularly object-naming, maintain their role as gold standards. Automated speech tasks are used to detect speech errors and to set the amplitude of the stimulator. Comprehension tasks, reading and writing tasks, and tasks that assess grammatical aspects of language may be regularly administered in the near future. We provide examples of a three-task approach we are administering to patients with prefrontal lesions. We believe that future advances in this area are contingent upon reviewing gold standards and introducing new assessment tools. PMID- 26159551 TI - The use of TachoSil(r) associated to fibrin glue as dural sealant in spinal intradural tumors surgery. PMID- 26159552 TI - Low frequency of delayed ischemic events on MRI after flow diversion for intracranial aneurysms. AB - BACKGROUND: The rate of silent ischemia detected on Magnetic Resonance Imaging (MRI) in the long-term follow-up period following endovascular treatment of intracranial aneurysms with the Pipeline Embolization Device (PED) is not well established. The purpose of this study was to evaluate the occurrence rate of silent ischemia detected on MRI in patients undergoing treatment of intracranial aneurysms with PED receiving at least 6 months of MRI follow-up. METHODS: We evaluated our institution's database of patients receiving PED treatment of intracranial aneurysms. Imaging records were searched to identify which patients received an MRI at least six-months postoperatively. MR images were reviewed for evidence of new infarction and medical records were reviewed to determine the clinical outcome. RESULTS: Of the 68 patients with MR imaging following aneurysm treatment with PED, 40 patients had an MRI at least six months following treatment with the PED. Of patients with MRI at >=6 months following PED treatment, 2/40 (5.0%) had a new infarct. Of these, one had a lacunar infarct which was likely non-embolic and one patient had a punctate infarction in the contralateral centrum semiovale. None of these infarcts were symptomatic. CONCLUSIONS: In this study, a small number of silent ischemic events (5.0%) was found on routine long-term follow-up MRI of patients undergoing flow diversion. These events did not lead to any neurologic deficits. Our findings add to the available evidence on the long-term safety of flow diversion for the treatment of intracranial aneurysms. PMID- 26159553 TI - Ethnicity and coronary artery disease: the role of high-density lipoprotein - a change in paradigm. AB - Cardiovascular disease (CVD) is the number one killer of men and women across ethnic groups in the USA. Health disparities in CVD, especially coronary artery disease (CAD), are well documented in the diverse American population. Despite efforts taken toward reducing cardiovascular health disparities, there are still gaps in its diagnosis and management. Current risk assessment guidelines consider high high-density lipoprotein (HDL) levels a protective factor against CAD, although its significance across races remains poorly understood. Recent clinical trials focused on increasing HDL levels have been disappointing. In this article, the authors have explored the role of HDL in CAD, have analyzed its significance across gender and ethnic groups and have challenged the broad application of widely used HDL level cutoffs in CAD risk assessment tools across these vulnerable groups. The current evidence suggests a paradigm change from HDL quantity to quality and function in future CVD risk research. This may better explain why some ethnic minority groups with a seemingly more benign lipid profile experience a higher CAD burden. PMID- 26159554 TI - Discover natural compounds as potential phosphodiesterase-4B inhibitors via computational approaches. AB - cAMP, intracellular cyclic adenosine monophosphate, is a ubiquitous second messenger that plays a key role in many physiological processes. PDE4B which can reduce the cAMP level by hydrolyzing cAMP to 5'-AMP has become a therapeutic target for the treatment of human diseases such as respiratory disorders, inflammation diseases, neurological and psychiatric disorders. However, the use of currently available PDE4B inhibitors is restricted due to serious side effects caused by targeting PDE4D. Hence, we are attempting to find out subfamily selective PDE4B inhibitors from natural products, using computer-aided approaches such as virtual screening, docking, and molecular dynamics simulation. Finally, four potential PDE4B-selective inhibitors (ZINC67912770, ZINC67912780, ZINC72320169, and ZINC28882432) were found. Compared to the reference drug (roflumilast), they scored better during the virtual screening process. Binding free energy for them was -317.51, -239.44, -215.52, and -165.77 kJ/mol, better than -129.05 kJ/mol of roflumilast. The pharmacophore model of the four candidate inhibitors comprised six features, including one hydrogen bond donor, four hydrogen bond acceptors, and one aromatic ring feature. It is expected that our study will pave the way for the design of potent PDE4B-selective inhibitors of new drugs to treat a wide variety of diseases such as asthma, COPD, psoriasis, depression, etc. PMID- 26159555 TI - Elective pelvic versus prostate bed-only salvage radiotherapy following radical prostatectomy: A propensity score-matched analysis. AB - PURPOSE: To compare the impact of elective whole pelvic radiotherapy (WPRT) versus prostate bed-only radiotherapy (PBRT) on biochemical relapse-free survival (bRFS) in prostate cancer patients treated with salvage radiotherapy following radical prostatectomy (RP). PATIENTS AND METHODS: In our database, 163 lymph node negative prostate cancer patients who had undergone salvage radiotherapy (SRT) for biochemical relapse after RP between September 2004 and April 2012 were identified. PBRT was administered to 134 patients (the PBRT group), while the remaining 29 patients (the WPRT group) received WPRT. RESULTS: Median follow-up was 57 months (range 18-122 months). In the propensity score-matched cohort, the 4-year bRFS of the WPRT group was significantly higher compared to the PBRT group (63.1 vs. 43.4%, p = 0.034). Subgroup analysis showed that the bRFS of patients who had two or more risk factors (seminal vesicle invasion, Roach score for lymph node invasion >= 45%, and number of harvested lymph nodes <= 5) and were treated with WPRT was significantly improved compared to those who received PBRT (hazard ratio, HR 0.33; 95% confidence interval, CI 0.13-0.83; p = 0.018). CONCLUSION: Elective WPRT for SRT may improve bRFS in patients with unfavorable risk factors. These results need to be confirmed by a prospective randomized trial. PMID- 26159556 TI - PGD2 deficiency exacerbates food antigen-induced mast cell hyperplasia. AB - Prostaglandin D2 (PGD2) is a major prostanoid secreted mainly by mast cells. Although PGD2 has been identified as a modulator of allergic inflammation, its precise role remains unclear. Here we investigate the role of PGD2 in food allergy. Oral administration of ovalbumin induces allergic responses in sensitized wild-type (WT) mice. Systemic gene deficiency of haematopoietic PGD synthase (H-PGDS(-/-)) exacerbates all of the manifestations accompanying severe mast cell hyperplasia in the intestine. Morphological studies show that c kit/FcERI-positive WT mast cells strongly express H-PGDS. Transplantation of H PGDS(-/-) mast cells also aggravates ovalbumin-induced mast cell hyperplasia and allergic symptoms in mast cell null mice. H-PGDS deficiency accelerates the production of SDF-1alpha and the activity of MMP-9 in the antigen-stimulated intestine. SDF-1alpha receptor blockade or MMP-9 inhibition relieves the exacerbated mast cell hyperplasia and manifestations observed in H-PGDS(-/-). Thus, PGD2 deficiency results in food antigen-induced mast cell hyperplasia. PMID- 26159557 TI - Association of three 8q24 polymorphisms with prostate cancer susceptibility: evidence from a meta-analysis with 50,854 subjects. AB - The 8q24 polymorphisms have been implicated in various cancers. Three 8q24 polymorphisms (rs1447295 C>A, rs16901979 C>A, and rs6983267 T>G) have been extensively investigated for their association with prostate cancer (PCa) susceptibility, yet conclusions are contradictory. We conducted a comprehensive meta-analysis to reevaluate the associations between those polymorphisms and PCa susceptibility, according to the latest meta-analysis guidelines (PRISMA). Eligible publications were searched from MEDLINE, EMBASE and CBM. False positive report possibility analysis was performed. We totally collected 20184 cases and 20439 controls from 20 studies for the rs1447295 C>A, 1850 cases and 2090 controls from 7 studies for the rs16901979 C>A, and 12233 cases and 7582 controls from 17 studies for the rs6983267 T>G. Overall, each of studied 8q24 polymorphisms was significantly associated with PCa risk individually. Significant associations were also observed in stratified analysis by ethnicity, source of control, and quality score. Interestingly, the effect of rs1447295 on PCa risk was observed among Caucasians and Asians, but not Africa-Americans. The effect of rs16901979 was more prominent among Africa-Americans than Asians. Likewise, rs6983267 conferred a higher Pca risk among Caucasians than Asians. Collectively, these 8q24 variant(s) may modulate PCa risk in an ethnic-specific manner. PMID- 26159558 TI - Giant rotating magnetocaloric effect induced by highly texturing in polycrystalline DyNiSi compound. AB - Large rotating magnetocaloric effect (MCE) has been observed in some single crystals due to strong magnetocrystalline anisotropy. By utilizing the rotating MCE, a new type of rotary magnetic refrigerator can be constructed, which could be more simplified and efficient than the conventional one. However, compared with polycrystalline materials, the high cost and complexity of preparation for single crystals hinder the development of this novel magnetic refrigeration technology. For the first time, here we observe giant rotating MCE in textured DyNiSi polycrystalline material, which is larger than those of most rotating magnetic refrigerants reported so far. This result suggests that DyNiSi compound could be attractive candidate of magnetic refrigerants for novel rotary magnetic refrigerator. By considering the influence of demagnetization effect on MCE, the origin of large rotating MCE in textured DyNiSi is attributed to the coexistence of strong magnetocrystalline anisotropy and highly preferred orientation. Our study on textured DyNiSi not only provides a new magnetic refrigerant with large rotating MCE for low temperature magnetic refrigeration, but also opens a new way to exploit magnetic refrigeration materials with large rotating MCE, which will be highly beneficial to the development of rotating magnetic refrigeration technology. PMID- 26159559 TI - "Reuse" study of low-tube-voltage CT arterial phase in the spoiled gadoxetic-acid liver MRI. AB - OBJECTIVES: To compare diagnostic accuracy of gadoxetic acid-enhanced magnetic resonance imaging (MRI) (original set) and original MRI combined with the arterial phase of low-tube-voltage computed tomography (CT) (hybrid set). METHODS: In hybrid set, we substituted the CT arterial phase for MRI arterial phase. Three observers independently interpreted. The accuracy of each image set was evaluated using the alternative-free response receiver operating characteristic method. RESULTS: The mean Az values for original set (0.96+/-0.01) was higher than that for hybrid set (0.94+/-0.01), but the difference was not significant (P=.10). CONCLUSIONS: In cases with degradation of magnetic resonance arterial phase, reuse of CT arterial phase might be helpful instead of repeating MRI. PMID- 26159560 TI - Hemodynamics in a Pediatric Ascending Aorta Using a Viscoelastic Pediatric Blood Model. AB - Congenital heart disease is the leading cause of infant death in the United States with over 36,000 newborns affected each year. Despite this growing problem there are few mechanical circulatory support devices designed specifically for pediatric and neonate patients. Previous research has been done investigating pediatric ventricular assist devices (PVADs) assuming blood to be a Newtonian fluid in computational fluid dynamics (CFD) simulations, ignoring its viscoelastic and shear-thinning properties. In contrast to adult VADs, PVADs may be more susceptible to hemolysis and thrombosis due to altered flow into the aorta, and therefore, a more accurate blood model should be used. A CFD solver that incorporates a modified Oldroyd-B model designed specifically for pediatric blood is used to investigate important hemodynamic parameters in a pediatric aortic model under pulsatile flow conditions. These results are compared to Newtonian blood simulations at three physiological pediatric hematocrits. Minor differences are seen in both velocity and wall shear stress (WSS) during early stages of the cardiac cycle between the Newtonian and viscoelastic models. During diastole, significant differences are seen in the velocities in the descending aorta (up to 12%) and in the aortic branches (up to 30%) between the two models. Additionally, peak WSS differences are seen between the models throughout the cardiac cycle. At the onset of diastole, peak WSS differences of 43% are seen between the Newtonian and viscoelastic model and between the 20 and 60% hematocrit viscoelastic models at peak systole of 41%. PMID- 26159561 TI - Dioxins from medical waste incineration: Normal operation and transient conditions. AB - Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are key pollutants in waste incineration. At present, incinerator managers and official supervisors focus only on emissions evolving during steady state operation. Yet, these emissions may considerably be raised during periods of poor combustion, plant shutdown, and especially when starting-up from cold. Until now there were no data on transient emissions from medical (or hospital) waste incineration (MWI). However, MWI is reputed to engender higher emissions than those from municipal solid waste incineration (MSWI). The emission levels in this study recorded for shutdown and start-up, however, were significantly higher: 483 +/- 184 ng Nm(-3) (1.47 +/- 0.17 ng I-TEQ Nm(-3)) for shutdown and 735 ng Nm(-3) (7.73 ng I-TEQ Nm(-3)) for start-up conditions, respectively. Thus, the average (I-TEQ) concentration during shutdown is 2.6 (3.8) times higher than the average concentration during normal operation, and the average (I-TEQ) concentration during start-up is 4.0 (almost 20) times higher. So monitoring should cover the entire incineration cycle, including start-up, operation and shutdown, rather than optimised operation only. This suggestion is important for medical waste incinerators, as these facilities frequently start up and shut down, because of their small size, or of lacking waste supply. Forthcoming operation should shift towards much longer operating cycles, i.e., a single weekly start-up and shutdown. PMID- 26159562 TI - Feasibility study for retrofitting biogas cogeneration systems to district heating in South Korea. AB - A feasibility study was performed to assess the technical and economic merits of retrofitting biogas-based cogeneration systems to district heating networks. Three district heating plants were selected as candidates for accommodating heat recovery from nearby waste treatment stations, where a massive amount of biogas can be produced on a regular basis. The scenario involves constructing cogeneration systems in each waste treatment station and producing electricity and heat. The amounts of biogas production for each station are estimated based on the monthly treatment capacities surveyed over the most recent years. Heat produced by the cogeneration system is first consumed on site by the waste treatment system to keep the operating temperature at a proper level. If surplus heat is available, it will be transported to the nearest district heating plant. The year-round operation of the cogeneration system was simulated to estimate the electricity and heat production. We considered cost associated with the installation of the cogeneration system and piping as initial investments. Profits from selling electricity and recovering heat are counted as income, while costs associated with buying biogas are expenses. Simple payback periods of 2-10 years were projected under the current economic conditions of South Korea. We found that most of the proposed scenarios can contribute to both energy savings and environmental protection. PMID- 26159563 TI - A rare case of acute leukemia of ambiguous lineage overexpressing C-MYC with monosomy 7 and Philadelphia chromosome. PMID- 26159564 TI - Automated computational screening of the thiol reactivity of substituted alkenes. AB - Electrophilic olefins can react with the S-H moiety of cysteine side chains. The formation of a covalent adduct through this mechanism can result in the inhibition of an enzyme. The reactivity of an olefin towards cysteine depends on its functional groups. In this study, 325 reactions of thiol-Michael-type additions to olefins were modeled using density functional theory. All combinations of ethenes with hydrogen, methyl ester, amide, and cyano substituents were included. An automated workflow was developed to perform the construction, conformation search, minimization, and calculation of molecular properties for the reactant, carbanion intermediate, and thioether products for a model reaction of the addition of methanethiol to the electrophile. Known cysteine-reactive electrophiles present in the database were predicted to react exergonically with methanethiol through a carbanion with a stability in the 30-40 kcal mol(-1) range. 13 other compounds in our database that are also present in the PubChem database have similar properties. Natural bond orbital parameters were computed and regression analysis was used to determine the relationship between properties of the olefin electronic structure and the product and intermediate stability. The stability of the intermediates is very sensitive to electronic effects on the carbon where the anionic charge is centered. The stability of the products is more sensitive to steric factors. PMID- 26159565 TI - Modulation of superoxide dismutase (SOD) isozymes by organ development and high long-term salinity in the halophyte Cakile maritima. AB - Superoxide dismutase (SOD) activity catalyzes the disproportionation of superoxide radicals into hydrogen peroxide and oxygen. This enzyme is considered to be a first line of defense for controlling the production of reactive oxygen species (ROS). In this study, the number and type of SOD isozymes were identified in the principal organs (roots, stems, leaves, flowers, and seeds) of Cakile maritima. We also analyzed the way in which the activity of these SOD isozymes is modulated during development and under high long-term salinity (400 mM NaCl) stress conditions. The data indicate that this plant contains a total of ten SOD isozymes: two Mn-SODs, one Fe-SOD, and seven CuZn-SODs, with the Fe-SOD being the most prominent isozyme in the different organs analyzed. Moreover, the modulation of SOD isozymes, particularly CuZn-SODs, was only detected during development and under severe salinity stress conditions. These data suggest that, in C. maritima, the occurrence of these CuZn-SODs in roots and leaves plays an adaptive role since this CuZn-SOD isozyme might replace the diminished Fe-SOD activity under salinity stress to overcome this adverse environmental condition. PMID- 26159566 TI - Extracellular N-Acetylaspartate in Human Traumatic Brain Injury. AB - N-acetylaspartate (NAA) is an amino acid derivative primarily located in the neurons of the adult brain. The function of NAA is incompletely understood. Decrease in brain tissue NAA is presently considered symptomatic and a potential biomarker of acute and chronic neuropathological conditions. The aim of this study was to use microdialysis to investigate the behavior of extracellular NAA (eNAA) levels after traumatic brain injury (TBI). Sampling for this study was performed using cerebral microdialysis catheters (M Dialysis 71) perfused at 0.3 MUL/min. Extracellular NAA was measured in microdialysates by high-performance liquid chromatography in 30 patients with severe TBI and for comparison, in radiographically "normal" areas of brain in six non-TBI neurosurgical patients. We established a detailed temporal eNAA profile in eight of the severe TBI patients. Microdialysate concentrations of glucose, lactate, pyruvate, glutamate, and glycerol were measured on an ISCUS clinical microdialysis analyzer. Here, we show that the temporal profile of microdialysate eNAA was characterized by highest levels in the earliest time-points post-injury, followed by a steady decline; beyond 70 h post-injury, average levels were 40% lower than those measured in non-TBI patients. There was a significant inverse correlation between concentrations of eNAA and pyruvate; eNAA showed significant positive correlations with glycerol and the lactate/pyruvate (L/P) ratio measured in microdialysates. The results of this on-going study suggest that changes in eNAA after TBI relate to the release of intracellular components, possibly due to neuronal death or injury, as well as to adverse brain energy metabolism. PMID- 26159567 TI - Quality of life in rehabilitation outpatients: normal values and a comparison with the general Dutch population and psychiatric patients. AB - PURPOSE: To provide Dutch normal values for rehabilitation outpatients with chronic pain or musculoskeletal diseases utilizing the World Health Organization Quality of Life questionnaire abbreviated version (WHOQOL-BREF) and analyse influence of diagnosis and patient characteristics on normal values and increase understanding in those values. METHODS: Five hundred and forty-two outpatients were referred to a rehabilitation psychologist. Referral diagnoses were "musculoskeletal", "chronic pain", "neurological" and "miscellaneous". Comparisons between groups were made for each of the four domains of the WHOQOL BREF (scoring range 4-20). RESULTS: Domain scores of rehabilitation outpatients were physical domain 11.0 (+/-2.7), psychological domain 13.6 (+/-2.4), social domain 14.8 (+/-3.4) and environmental domain 14.2 (+/-2.2). Outpatients with chronic pain reported the lowest scores on the WHOQOL-BREF when compared to the "musculoskeletal", "neurological" and "miscellaneous" groups. Increased age, lower education, living alone and unemployment had a negative impact on WHOQOL BREF scores. Compared to the general Dutch population, rehabilitation outpatients scored, unadjusted for age, significantly lower difference for the physical domain 4.5 [95% confidence interval (CI) 4.2; 4.8], the environment domain 1.7 (95% CI 1.5; 2.0), the psychological domain 1.1 (95% CI 0.4; 1.2) and the social domain 0.4 (95% CI 0.0; 0.8). CONCLUSIONS: WHOQOL-BREF scores of rehabilitation outpatients are lower and differed significantly from normal values of a Dutch population in all four domains. Therefore, the WHOQOL-BREF can be used to measure the subjective impact of their disease or injury. The subjective impact of chronic pain was found to be particularly high. PMID- 26159568 TI - Stimulation of Wnt/beta-Catenin Signaling to Improve Bone Development by Naringin via Interacting with AMPK and Akt. AB - BACKGROUND/AIMS: Naringin is a naturally existing compound in citrus fruits and has been elucidated to promote bone development and maintenance. METHODS: The biological roles of naringin were investigated in vitro using osteoblast-like UMR 106 cells, and in vivo through performing ovariectomy to mimic osteoporosis in female mice. Since Wnt/beta-catenin signaling is involved in osteoblastogenesis, the effect of naringin on Wnt/beta-catenin signaling was studied. RESULTS: Naringin promoted the mRNA and protein expressions of beta-catenin, and improved Ser552 phosphorylation on beta-catenin in UMR-106 cells, which leads to the activation of lymphoid enhancer factor (LEF)/ T-cell factor (TCF) transcription factors. The recruitments of protein kinase B (Akt) inhibitor (Akti-1/2) and AMP activated protein kinase (AMPK) inhibitor (Dorsomorphin) reduced the influence of naringin on beta-catenin phosphorylation, suggesting naringin activates beta catenin via regulating Akt and AMPK. In ovariectomized (OVX) mice naringin treatment improved the bone strength while AMPK and Akt inhibitors partly reversed the effect, which further proved the involvements of Akt and AMPK in the action of naringin in vivo. CONCLUSION: Our study points to a novel finding on the mechanism of naringin in facilitating bone formation via Akt and AMPK signaling. PMID- 26159571 TI - Application of capillary electrophoresis with electrokinetic supercharging and sweeping for the on-line preconcentration of phenolic acids. AB - Phenolic acids are natural antioxidants. Many studies have confirmed that these compounds can reduce the risk of developing chronic diseases such as diabetes, cardiovascular diseases, and certain cancers. In this work, we developed a rapid and efficient capillary electrophoresis method with an on-line preconcentration technique that could be used to simultaneously analyze 10 commonly found phenolic acids in plants. Briefly, phosphate buffer solution (pH 2) was filled into an uncoated fused silica capillary as the leading electrolyte, and then samples which were prepared in borate buffer (as the terminating ion) were loaded by electrokinetic injection (-10 kV, 900 s). After sample injection, both ends of the capillary were switched to the vial containing phosphate buffer with sodium dodecyl sulfate. The separation was then performed in micellar electrokinetic chromatography (MEKC) mode at -20 kV. During the method validation, the correlation coefficient of the regression curve was measured as greater than 0.997 and the relative standard deviation and relative error were lower than 9.63 % and 4.7 %, respectively. The limits of detection (LODs, S/N = 3) of these 10 analytes ranged from 0.01 to 2.5 ng/mL. Compared with the conventional capillary zone electrophoresis (CZE) method, the sensitivity for the analytes could be increased up to 25,000-fold. The method that we developed here was applied successfully to the detection of phenolic acids in fruit juices. PMID- 26159570 TI - Indirect detection of superoxide in RAW 264.7 macrophage cells using microchip electrophoresis coupled to laser-induced fluorescence. AB - Superoxide, a naturally produced reactive oxygen species (ROS) in the human body, is involved in many pathological and physiological signaling processes. However, if superoxide formation is left unregulated, overproduction can lead to oxidative damage to important biomolecules, such as DNA, lipids, and proteins. Superoxide can also lead to the formation of peroxynitrite, an extremely hazardous substance, through its reaction with endogenously produced nitric oxide. Despite its importance, quantitative information regarding superoxide production is difficult to obtain due to its high reactivity and low concentrations in vivo. MitoHE, a fluorescent probe that specifically reacts with superoxide, was used in conjunction with microchip electrophoresis (ME) and laser-induced fluorescence (LIF) detection to investigate changes in superoxide production by RAW 264.7 macrophage cells following stimulation with phorbol 12-myristate 13-acetate (PMA). Stimulation was performed in the presence and absence of the superoxide dismutase (SOD) inhibitors, diethyldithiocarbamate (DDC) and 2-metoxyestradiol (2 ME). The addition of these inhibitors resulted in an increase in the amount of superoxide specific product (2-OH-MitoE(+)) from 0.08 +/- 0.01 fmol (0.17 +/- 0.03 mM) in native cells to 1.26 +/- 0.06 fmol (2.5 +/- 0.1 mM) after PMA treatment. This corresponds to an approximately 15-fold increase in intracellular concentration per cell. Furthermore, the addition of 3-morpholino-sydnonimine (SIN-1) to the cells during incubation resulted in the production of 0.061 +/- 0.006 fmol (0.12 +/- 0.01 mM) of 2-OH-MitoE(+) per cell on average. These results demonstrate that indirect superoxide detection coupled with the use of SOD inhibitors and a separation method is a viable method to discriminate the 2-OH MitoE(+) signal from possible interferences. PMID- 26159569 TI - In-depth LC-MS/MS analysis of the chicken ovarian cancer proteome reveals conserved and novel differentially regulated proteins in humans. AB - Ovarian cancer (OVC) remains the most lethal gynecological malignancy in the world due to the combined lack of early-stage diagnostics and effective therapeutic strategies. The development and application of advanced proteomics technology and new experimental models has created unique opportunities for translational studies. In this study, we investigated the ovarian cancer proteome of the chicken, an emerging experimental model of OVC that develops ovarian tumors spontaneously. Matched plasma, ovary, and oviduct tissue biospecimens derived from healthy, early-stage OVC, and late-stage OVC birds were quantitatively characterized by label-free proteomics. Over 2600 proteins were identified in this study, 348 of which were differentially expressed by more than twofold (p <= 0.05) in early- and late-stage ovarian tumor tissue specimens relative to healthy ovarian tissues. Several of the 348 proteins are known to be differentially regulated in human cancers including B2M, CLDN3, EPCAM, PIGR, S100A6, S100A9, S100A11, and TPD52. Of particular interest was ovostatin 2 (OVOS2), a novel 165-kDa protease inhibitor found to be strongly upregulated in chicken ovarian tumors (p = 0.0005) and matched plasma (p = 0.003). Indeed, RT quantitative PCR and Western blot analysis demonstrated that OVOS2 mRNA and protein were also upregulated in multiple human OVC cell lines compared to normal ovarian epithelia (NOE) cells and immunohistochemical staining confirmed overexpression of OVOS2 in primary human ovarian cancers relative to non cancerous tissues. Collectively, these data provide the first evidence for involvement of OVOS2 in the pathogenesis of both chicken and human ovarian cancer. PMID- 26159572 TI - Cleaning-in-place of immunoaffinity resins monitored by in situ ATR-FTIR spectroscopy. AB - In the next 10 years, the pharmaceutical industry anticipates that revenue from biotherapeutics will overtake those generated from small drug molecules. Despite effectively treating a range of chronic and life-threatening diseases, the high cost of biotherapeutics limits their use. For biotherapeutic monoclonal antibodies (mAbs), an important production cost is the affinity resin used for protein capture. Cleaning-in-place (CIP) protocols aim to optimise the lifespan of the resin by slowing binding capacity decay. Binding assays can determine resin capacity from the mobile phase, but do not reveal the underlying causes of Protein A ligand degradation. The focus needs to be on the stationary phase to examine the effect of CIP on the resin. To directly determine both the local Protein A ligand concentration and conformation on two Protein A resins, we developed a method based on attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy. ATR-FTIR spectroscopic imaging revealed that applying a carefully controlled load to agarose beads produces an even and reproducible contact with the internal reflection element. This allowed detection and quantification of the binding capacity of the stationary phase. ATR-FTIR spectroscopy also showed that Protein A proteolysis does not seem to occur under typical CIP conditions (below 1 M NaOH). However, our data revealed that concentrations of NaOH above 0.1 M cause significant changes in Protein A conformation. The addition of >0.4 M trehalose during CIP significantly reduced NaOH-induced ligand unfolding observed for one of the two Protein A resins tested. Such insights could help to optimise CIP protocols in order to extend resin lifetime and reduce mAb production costs. PMID- 26159573 TI - Combining vibrational biomolecular spectroscopy with chemometric techniques for the study of response and sensitivity of molecular structures/functional groups mainly related to lipid biopolymer to various processing applications. AB - The objectives of this project were to (1) combine vibrational spectroscopy with chemometric multivariate techniques to determine the effect of processing applications on molecular structural changes of lipid biopolymer that mainly related to functional groups in green- and yellow-type Crop Development Centre (CDC) pea varieties [CDC strike (green-type) vs. CDC meadow (yellow-type)] that occurred during various processing applications; (2) relatively quantify the effect of processing applications on the antisymmetric CH3 ("CH3as") and CH2 ("CH2as") (ca. 2960 and 2923 cm(-1), respectively), symmetric CH3 ("CH3s") and CH2 ("CH2s") (ca. 2873 and 2954 cm(-1), respectively) functional groups and carbonyl C=O ester (ca. 1745 cm(-1)) spectral intensities as well as their ratios of antisymmetric CH3 to antisymmetric CH2 (ratio of CH3as to CH2as), ratios of symmetric CH3 to symmetric CH2 (ratio of CH3s to CH2s), and ratios of carbonyl C=O ester peak area to total CH peak area (ratio of C=O ester to CH); and (3) illustrate non-invasive techniques to detect the sensitivity of individual molecular functional group to the various processing applications in the recently developed different types of pea varieties. The hypothesis of this research was that processing applications modified the molecular structure profiles in the processed products as opposed to original unprocessed pea seeds. The results showed that the different processing methods had different impacts on lipid molecular functional groups. Different lipid functional groups had different sensitivity to various heat processing applications. These changes were detected by advanced molecular spectroscopy with chemometric techniques which may be highly related to lipid utilization and availability. The multivariate molecular spectral analyses, cluster analysis, and principal component analysis of original spectra (without spectral parameterization) are unable to fully distinguish the structural differences in the antisymmetric and symmetric CH3 and CH2 spectral region (ca. 3001-2799 cm(-1)) and carbonyl C=O ester band region (ca. 1771-1714 cm(-1)). This result indicated that the sensitivity to detect treatment difference by multivariate analysis of cluster analysis (CLA) and principal components analysis (PCA) might be lower compared with univariate molecular spectral analysis. In the future, other more sensitive techniques such as "discriminant analysis" could be considered for discriminating and classifying structural differences. Molecular spectroscopy can be used as non-invasive technique to study processing-induced structural changes that are related to lipid compound in legume seeds. PMID- 26159574 TI - The Forgotten Variable of Shear Stress in Mitral Annular Calcification: Whole Blood Viscosity. AB - OBJECTIVE: The aim of this research was to assess the relationship between mitral annular calcification (MAC) and whole blood viscosity (WBV). SUBJECTS AND METHODS: A total of 184 patients with MAC and 133 patients without MAC were enrolled in the study. The WBV was calculated with a confirmed formulation using the hematocrit and total plasma protein at a low shear rate (LSR) and high shear rate (HSR). Early diastolic mitral annular velocity (Ea) and late diastolic mitral annular velocity (Aa) were measured using pulse Doppler tissue echocardiography. Pearson's correlation analysis was performed to assess the relationship between WBV and mitral annular motion velocities. The effects of different variables on the occurrence of MAC were assessed in univariate and multivariate logistic regression analysis. RESULTS: In patients with MAC, WBV values were significantly higher at HSR (18.04 +/- 0.84 vs. 17.25 +/- 0.96 208 s( 1), p < 0.001) and at LSR (78.0 +/- 14.2 vs. 61.9 +/- 17.1 0.5 s(-1), p < 0.001). The WBV at HSR and LSR were significantly correlated with Ea (r = -0.477, p < 0.001; r = -0.385, p < 0.001, respectively) and Aa (r = -0.544, p < 0.001; r = 0.323, p < 0.001, respectively). Multivariate analysis showed that WBV of both shear rates was an independent predictor of MAC. Using the ROC curve, a cut-off value of 70.1 for WBV at LSR had a sensitivity of 83.7% and a specificity of 73.7% (AUC 0.785, p < 0.001) and a WBV cut-off value of 17.5 at HSR had a sensitivity of 79.6% and a specificity of 71.4% (AUC 0.761, p < 0.001) for the prediction of MAC. CONCLUSION: Patients with MAC had significantly higher WBV, which independently predicted the presence of MAC. WBV had an inverse correlation with mitral annular motion velocities, indicating that a higher WBV may lead to greater limitation in annular motion and, thus, more calcification. PMID- 26159575 TI - Design of linear anti-scatter grid geometry with optimum performance for screen film and digital mammography systems. AB - A detailed 3D Monte Carlo simulation of the grid geometrical parameters in screen film mammography (SFM) and digital mammography (DM) systems has been performed. A combination of IEC 60627:2013 international standard conditions and other more clinically relevant parameters were used for this simulation. Accuracy of our results has been benchmarked with previously published data and good agreement has been obtained. Calculations in a wide range of linear anti-scatter grid geometries have been carried out. The evaluated parameters for the SFM system were the Bucky factor (BF) and contrast improvement factor (CIF) and for the DM system it was signal difference-to-noise ratio improvement factor (SIF). The CIF parameter was chosen to be nearly the same as the commercial grade, the BF and SIF were significantly improved compared to commercial grids in use today. Our optimized grid parameters for the SFM system were lead strip thickness d = 12 um, grid ratio r = 5 and strip density N = 65 lines/cm. And for the DM system these parameters were d = 5 um, r = 3 and N = 100 lines/cm. Both optimized grid sets have thinner d and higher N compared to the commercial grids. PMID- 26159576 TI - Screening of quinoline, 1,3-benzoxazine, and 1,3-oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis. AB - Elevated activity of methionyl-tRNA synthetase (MRS) in many cancers renders it a possible drug target in this disease area, as well as in a series of parasitic diseases. In the present work, we report the synthesis and in vitro screening of a library of 1,3-oxazines, benzoxazines and quinoline scaffolds against human MRS. Among the compounds tested, 2-(2-butyl-4-chloro-1-(4-phenoxybenzyl)-1H imidazol-5-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane (compound 21) and 2-(2-butyl-4-chloro-1-(4-nitrobenzyl)-1H-imidazol-5-yl)-2,4-dihydro-1H benzo[d][1,3]oxazine (compound 8) were found to be potent inhibitors of MRS. Additionally, these compounds significantly suppressed the proliferation of A549 and HCT116 cells with IC50 values of 28.4, 17.7, 41.9, and 19.8 MUM respectively. Molecular docking studies suggested that the ligand binding orientation overlaps with the original positions of both methionine and adenosine of MRS. This suggests the binding of compound 21 against MRS, which might lead the inhibitory activity towards cancer cells. PMID- 26159577 TI - Prevalence and Related Risk Factors of Overweight and Obesity among the Adult Population in the Balearic Islands, a Mediterranean Region. AB - OBJECTIVE: To assess the prevalence and risk factors of overweight (OW) and obesity (OB) by BMI and abdominal obesity (AO) by waist-to-height ratio, (WHtR) among the Balearic Islands' adult population. METHODS: Cross-sectional nutritional survey carried out in the Balearic Islands (2009-2010). A random sample (n = 1,081) of young (18-35 years) and middle-aged adults (36-55 years) were interviewed and anthropometrically measured. OW (BMI 25.0-29.9 kg/m(2)) and OB (BMI >= 30 kg/m(2)) were defined according to WHO criteria. AO was defined as WHtR >= 0.5. Socio-economic and lifestyle determinants were considered. RESULTS: The overall prevalence of OW/OB and AO was 29.4% (95% confidence interval (95% CI) 26.9-32.3%), 11.2% (95% CI 9.5-13.2%) and 33.1% (95% CI 30.4-36.0%), respectively. Men showed higher prevalence of OW (35.9%, 95% CI 31.6-40.5%) and AO (37.9%, 95% CI 33.6-42.5%) than women (OW 24.9%, 95% CI 21.7-28.4%; AO 29.7%, 95%CI 26.2-33.4%). Overall prevalence of OB was 11.8% (95% CI 9.1-15.1%) in men and 10.8% (95% CI 8.6-13.5%) in women. Age and no leisure-time physical activity (LTPA) were main risk factors associated with OW/OB and AO. Living with at least one child at home and to be married in men as well as to be unemployed, to be born in South America, and a low level of education in women were associated with AO. CONCLUSIONS: Men showed higher prevalence of OW and AO than women. In both sexes, age is the main risk factor associated with OW/OB and AO; in men also the absence of LTPA plays a significant role. PMID- 26159578 TI - Seroprevalence of anti-Toxoplasma IgG and IgM among individuals who were referred to medical laboratories in Mazandaran province, northern Iran. AB - Toxoplasma gondii (T. gondii) is a protozoan parasite that can cause toxoplasmosis in humans. However, there is no current data regarding Toxoplasma infection among individuals who were referred to medical laboratories in Mazandaran province (northern Iran). Therefore, we performed a population-based study of Toxoplasma seroprevalence in this region. A total of 1832 sera samples (from 654 men and 1178 women) were collected from people who were referred to medical laboratories in different cities throughout Mazandaran province between March and July 2012. The serum titers of anti-T. gondii IgG and IgM were measured using enzyme-linked immunosorbent assays. The seroprevalence of anti-Toxoplasma IgG was 55.5%; and 14.4% of the positive samples were seropositive for anti Toxoplasma IgM. The highest seroprevalence was observed among people who were >50 years old (90.6%), and the lowest seroprevalence was observed among children who were 0-9 years old (9.4%; P<0.001). There was no significant difference in the seroprevalences for each sex in the study population. However, a regional sex specific difference in seroprevalence was observed between men (54.1%) and women (70.6%; P=0.003) in the western cities of Mazandaran. As the seroprevalence of T. gondii in western and eastern Mazandaran was higher than that in the central cities, there is a need to evaluate the nature of the infection chain in these areas. PMID- 26159579 TI - Mechanical properties of a bioabsorbable nerve guide tube for long nerve defects. AB - The mechanical properties of nerve guide tubes must be taken into consideration when they are being developed. We previously reported the feasibility of using 50:50 tubes in a canine 40mm peroneal nerve defect model, where 50:50 represents the proportion of poly(L-lactic) acid (PLLA) and polyglycolic acid (PGA). The aim of the current study was to show that 50:50 tubes have suitable mechanical properties for repairing long nerve defects. Four types of nerve guide tubes made with PLLA to PGA fiber ratios of 100:0 (i.e. 100% PLLA) (100:0 tube), 50:50 (50:50 tube), 10:90 (10:90 tube), and 0:100 (0:100 tube) were designed and created using a tubular braiding machine. Their mechanical properties were examined in vitro (up to 16 weeks). In compression testing, 50:50 tubes had the highest normalized force value, followed in order by the 100:0, 10:90, and 0:100 tubes up to 8 weeks after immersion. From the point of view of biomechanics and bioresorbability, out of the 4 tube types tested, 50:50 tubes appeared to have the optimal mechanical properties for longer nerve defects. PMID- 26159580 TI - Transfer of the rhomboid nerve to the suprascapular nerve: An anatomical feasibility study. AB - Paralysis of the suprascapular nerve, in partial injuries of the brachial plexus, most often warrants a nerve transfer. Transfer of the spinal accessory nerve to the suprascapular nerve is performed most often. We propose to directly transfer the nerve of the rhomboid muscles (branch of the dorsal scapular nerve) to the suprascapular nerve in the supraspinatus fossa. This anatomical study included 10 shoulders. Dissection of the suprascapular nerve and the branch of dorsal scapular nerve to rhomboid muscles (rhomboid nerve) was performed through a posterior approach. Once the nerves were freed, the possibility of suturing the two nerves together was evaluated. Tensionless suture of the rhomboid nerve to the suprascapular nerve was possible in all shoulders in this study. In addition, the diameter of the two nerves was macroscopically compatible: the average diameter of the rhomboid and suprascapular nerve was 2.9 and 3mm, respectively. The diameter of the rhomboid nerve is more suitable than that of the spinal accessory nerve for a transfer to the suprascapular nerve. Moreover, the spinal accessory nerve is preserved in this technique, thereby preserving the function of the trapezius muscle, which could be used for muscle transfer if the nerve surgery fails. In addition, use of the rhomboid nerve allows the suture to be performed downstream to the suprascapular notch and avoids poor results linked to multilevel injuries of this nerve. Finally, if the posterior approach is extended laterally, associated transfer of the nerve to the long head of the triceps brachii to the axillary nerve is also possible. Rhomboid nerve transfer to the suprascapular nerve is anatomically possible. A clinical study will now be necessary to confirm this hypothesis and set out preliminary results. PMID- 26159581 TI - Old Weapons for New Wars: Bioactive Molecules From Cnidarian Internal Defense Systems. AB - The renewed interest in the study of genes of immunity in Cnidaria has led to additional information to the scenario of the first stages of immunity evolution revealing the cellular processes involved in symbiosis, in the regulation of homeostasis and in the fight against infections. The recent study with new molecular and functional approach on these organisms have therefore contributed with unexpected information on the knowledge of the stages of capturing activities and defense mechanisms strongly associated with toxin production. Cnidarians are diblastic aquatic animals with radial symmetry; they represent the ancestral state of Metazoa, they are the simplest multicellular organisms that have reached the level of tissue organization.The Cnidaria phylum has evolved using biotoxins as defense or predation mechanisms for ensure survival in hostile and competitive environments such as the seas and oceans. From benthic and pelagic species a large number of toxic compounds that have been determined can have an active role in the development of various antiviral, anticancer and antibacterial functions. Although the immune defense response of these animals is scarcely known, the tissues and the mucus produced by cnidarians are involved in immune defense and contain a large variety of peptides such as sodium and potassium channel neurotoxins, cytolysins, phospholipase A2 (PLA2), acid-sensing ion channel peptide toxins (ASICs) and other toxins, classified following biochemical and pharmacological studies on the basis of functional, molecular and structural parameters. These basal metazoan in fact, are far from "simple" in the range of methods at their disposal to deal with potential prey but also invading microbes and pathogens. They could also take advantage of the multi-functionality of some of their toxins, for example, some bioactive molecules have characteristics of toxicity associated with a potential antimicrobial activity. The interest in cnidarians was not only directed to the study of toxins and venom, but also to the fact these animals have been suggested as source of new molecules potentially relevant for biotechnology and pharmaceutical applications. Here, we review the cnidarian type of toxins regarding their multifunctional role and the future possibility of drawing important applications in fields ranging from biology to pharmacology. PMID- 26159582 TI - Combined Quantitative Assessment of Myocardial Perfusion and Coronary Artery Calcium Score by Hybrid 82Rb PET/CT Improves Detection of Coronary Artery Disease. AB - Hybrid PET myocardial perfusion imaging (MPI) with CT allows the incorporation of coronary artery calcium (CAC) into the clinical protocol. We aimed to determine whether the combined analysis of MPI and CAC could improve the diagnostic accuracy of PET MPI in detection of obstructive coronary artery disease (CAD). METHODS: Consecutive patients (n = 152; mean age +/- SD, 69 +/- 12 y) without prior CAD, referred to (82)Rb PET MPI followed by invasive coronary angiography performed within 14 days, were studied. Myocardial perfusion was quantified automatically for left anterior descending, left circumflex, and right coronary artery territories as an ischemic total perfusion deficit (ITPD) for 456 vessels. Global and per-vessel CAC Agatston scores were calculated. Obstructive CAD was defined as 50% or greater stenosis of the left main and 70% or greater stenosis in the left anterior descending, left circumflex, and right coronary arteries. Logistic regression and 10-fold cross validation were used to derive and validate the combined ITPD/logCAC (logarithm of coronary calcium) scores. RESULTS: In the prediction of per-vessel obstructive CAD, the receiver-operating-characteristic area under the curve for combined per-vessel ITPD/logCAC score was higher, 0.85 (95% confidence interval [CI], 0.81-0.89), than standalone ITPD area under the curve, 0.81 (95% CI: 0.76-0.85), and logCAC score, 0.73 (95% CI, 0.68-0.78; P < 0.05). The integrated discrimination improvement of combined per-vessel ITPD/logCAC analysis was 0.07 (95% CI, 0.04-0.09; P < 0.0001), as compared with ITPD alone. CONCLUSION: Combined automatically derived per-vessel ITPD and logCAC score improves accuracy of (82)Rb PET MPI for detection of obstructive CAD. PMID- 26159583 TI - How Should Lumped Constant Be Estimated for Hepatic 18F-FDG Glucose in Humans? PMID- 26159584 TI - Alzheimer Disease: Approaches to Early Diagnosis and High-Accuracy Imaging. PMID- 26159585 TI - Phantom and Clinical Evaluation of the Bayesian Penalized Likelihood Reconstruction Algorithm Q.Clear on an LYSO PET/CT System. AB - Q.Clear, a Bayesian penalized-likelihood reconstruction algorithm for PET, was recently introduced by GE Healthcare on their PET scanners to improve clinical image quality and quantification. In this work, we determined the optimum penalization factor (beta) for clinical use of Q.Clear and compared Q.Clear with standard PET reconstructions. METHODS: A National Electrical Manufacturers Association image-quality phantom was scanned on a time-of-flight PET/CT scanner and reconstructed using ordered-subset expectation maximization (OSEM), OSEM with point-spread function (PSF) modeling, and the Q.Clear algorithm (which also includes PSF modeling). Q.Clear was investigated for beta (B) values of 100 1,000. Contrast recovery (CR) and background variability (BV) were measured from 3 repeated scans, reconstructed with the different algorithms. Fifteen oncology body (18)F-FDG PET/CT scans were reconstructed using OSEM, OSEM PSF, and Q.Clear using B values of 200, 300, 400, and 500. These were visually analyzed by 2 scorers and scored by rank against a panel of parameters (overall image quality; background liver, mediastinum, and marrow image quality; noise level; and lesion detectability). RESULTS: As beta is increased, the CR and BV decreases; Q.Clear generally gives a higher CR and lower BV than OSEM. For the smallest sphere reconstructed with Q.Clear B400, CR is 28.4% and BV 4.2%, with corresponding values for OSEM of 24.7% and 5.0%. For the largest hot sphere, Q.Clear B400 yields a CR of 75.2% and a BV of 3.8%, with corresponding values for OSEM of 64.4% and 4.0%. Scorer 1 and 2 ranked B400 as the preferred reconstruction in 13 of 15 (87%) and 10 of 15 (73%) cases. The least preferred reconstruction was OSEM PSF in all cases. In most cases, lesion detectability was highest ranked for B200, in 9 of 15 (67%) and 10 of 15 (73%), with OSEM PSF ranked lowest. Poor lesion detectability on OSEM PSF was seen in cases of mildly (18)F-FDG-avid mediastinal nodes in lung cancer and small liver metastases due to background noise. Conversely, OSEM PSF was ranked second highest for lesion detectability in most pulmonary nodule evaluation cases. The combined scores confirmed B400 to be the preferred reconstruction. CONCLUSION: Our phantom measurement results demonstrate improved CR and reduced BV when using Q.Clear instead of OSEM. A beta value of 400 is recommended for oncology body PET/CT using Q.Clear. PMID- 26159586 TI - Gastrointestinal Motility, Part 2: Small-Bowel and Colon Transit. AB - Because of the difficulty often encountered in deciding whether a patient's symptoms originate in the upper or lower gastrointestinal tract, gastrointestinal transit scintigraphy is a uniquely suited noninvasive, quantitative, and physiologic method of determining whether there is a motility disorder affecting the stomach, small bowel, or colon. Small-bowel and colon transit studies can be performed alone or together with gastric emptying studies after oral administration of an appropriately radiolabeled meal. It is hoped that newly published standards for performing these studies and the anticipated arrival of new Current Procedural Terminology codes in the United States for small-bowel and colon transit studies will increase their availability and use. PMID- 26159587 TI - 18F-FDG PET/CT to Predict Response to Neoadjuvant Chemotherapy and Prognosis in Inflammatory Breast Cancer. AB - The aim of this prospective study was to assess the predictive value of (18)F-FDG PET/CT imaging for pathologic response to neoadjuvant chemotherapy (NACT) and outcome in inflammatory breast cancer (IBC) patients. METHODS: Twenty-three consecutive patients (51 y +/- 12.7) with newly diagnosed IBC, assessed by PET/CT at baseline (PET1), after the third course of NACT (PET2), and before surgery (PET3), were included. The patients were divided into 2 groups according to pathologic response as assessed by the Sataloff classification: pathologic complete response for complete responders (stage TA and NA or NB) and non pathologic complete response for noncomplete responders (not stage A for tumor or not stage NA or NB for lymph nodes). In addition to maximum standardized uptake value (SUVmax) measurements, a global breast metabolic tumor volume (MTV) was delineated using a semiautomatic segmentation method. Changes in SUVmax and MTV between PET1 and PET2 (DeltaSUV1-2; DeltaMTV1-2) and PET1 and PET3 (DeltaSUV1-3; DeltaMTV1-3) were measured. RESULTS: Mean SUVmax on PET1, PET2, and PET3 did not statistically differ between the 2 pathologic response groups. On receiver operating-characteristic analysis, a 72% cutoff for DeltaSUV1-3 provided the best performance to predict residual disease, with sensitivity, specificity, and accuracy of 61%, 80%, and 65%, respectively. On univariate analysis, the 72% cutoff for DeltaSUV1-3 was the best predictor of distant metastasis-free survival (P = 0.05). On multivariate analysis, the 72% cutoff for DeltaSUV1-3 was an independent predictor of distant metastasis-free survival (P = 0.01). CONCLUSION: Our results emphasize the good predictive value of change in SUVmax between baseline and before surgery to assess pathologic response and survival in IBC patients undergoing NACT. PMID- 26159589 TI - Diabody Pretargeting with Click Chemistry In Vivo. AB - Radioimmunotherapy and nuclear imaging (immuno-PET/SPECT) of cancer with radiometal-labeled antibody fragments or peptides is hampered by low tumor-to kidney ratios because of high renal radiometal retention. Therefore, we developed and evaluated a pretargeting strategy using click chemistry in vivo to reduce kidney uptake and avoid unwanted radiation toxicity. We focused on the bioorthogonal reaction between a trans-cyclooctene (TCO)-functionalized TAG72 targeting diabody, AVP04-07, and a low-molecular-weight radiolabeled tetrazine probe that was previously shown to have low kidney retention and relatively fast renal clearance. METHODS: AVP04-07 diabodies were functionalized with TCO tags, and in vitro immunoreactivity toward bovine submaxillary mucin and tetrazine reactivity were assessed. Next, pretargeting biodistribution studies were performed in LS174T tumor-bearing mice with AVP04-07-TCO(n) (where n indicates the number of TCO groups per diabody) and radiolabeled tetrazine to optimize the TCO modification grade (0, 1.8, or 4.7 TCO groups per diabody) and the (177)Lu tetrazine dose (0.1, 1.0, or 10 Eq with respect to the diabody). Radiolabeled tetrazine was injected at 47 h after diabody injection, and mice were euthanized 3 h later. A pretargeting SPECT/CT study with (111)In-tetrazine was performed with the optimized conditions. RESULTS: Immunoreactivity for native AVP04-07 was similar to that for TCO-functionalized AVP04-07, and the latter reacted efficiently with radiolabeled tetrazine in vitro. The combination of the pretargeting component AVP04-07 functionalized with 4.7 TCO groups and 1 Eq of (177)Lu-tetrazine with respect to the diabody showed the most promising biodistribution. Specifically, high (177)Lu-tetrazine tumor uptake (6.9 percentage injected dose/g) was observed with low renal retention, yielding a tumor-to-kidney ratio of 5.7. SPECT/CT imaging confirmed the predominant accumulation of radiolabeled tetrazine in the tumor and low nontumor retention. CONCLUSION: Pretargeting provides an alternative radioimmunotherapy and nuclear imaging strategy by overcoming the high renal retention of low-molecular-weight radiometal tumor-homing agents through the separate administration of a tumor homing agent and a radioactive probe with fast clearance. PMID- 26159588 TI - Image Quality and Diagnostic Performance of a Digital PET Prototype in Patients with Oncologic Diseases: Initial Experience and Comparison with Analog PET. AB - We report our initial clinical experience for image quality and diagnostic performance of a digital PET prototype scanner with time-of-flight (DigitalTF), compared with an analog PET scanner with time-of-flight (GeminiTF PET/CT). METHODS: Twenty-one oncologic patients, mean age 58 y, first underwent clinical (18)F-FDG PET/CT on the GeminiTF. The scanner table was then withdrawn while the patient remained on the table, and the DigitalTF was inserted between the GeminiTF PET and CT scanner. The patients were scanned for a second time using the same PET field of view with CT from the GeminiTF for attenuation correction. Two interpreters reviewed the 2 sets of PET/CT images for overall image quality, lesion conspicuity, and sharpness. They counted the number of suggestive (18)F FDG-avid lesions and provided the TNM staging for the 5 patients referred for initial staging. Standardized uptake values (SUVs) and SUV gradients as a measure of lesion sharpness were obtained. RESULTS: The DigitalTF showed better image quality than the GeminiTF. In a side-by-side comparison using a 5-point scale, lesion conspicuity (4.3 +/- 0.6), lesion sharpness (4.3 +/- 0.6), and diagnostic confidence (3.4 +/- 0.7) were better with DigitalTF than with GeminiTF (P < 0.01). In 52 representative lesions, the lesion maximum SUV was 36% higher with DigitalTF than with GeminiTF, lesion-to-blood-pool SUV ratio was 59% higher, and SUV gradient was 51% higher, with good correlation between the 2 scanners. Lesions less than 1.5 cm showed a greater increase in SUV from GeminiTF to DigitalTF than those lesions 1.5 cm or greater. In 5 of 21 patients, DigitalTF showed an additional 8 suggestive lesions that were not seen using GeminiTF. In the 15 restaging patients, the true-negative rate was 100% and true-positive rate was 78% for both scanners. In the 5 patients for initial staging, DigitalTF led to upstaging in 2 patients and showed the same staging in the other 3 patients, compared with GeminiTF. CONCLUSION: DigitalTF provides better image quality, diagnostic confidence, and accuracy than GeminiTF. DigitalTF may be the most beneficial in detecting small tumor lesions and disease staging. PMID- 26159590 TI - Methodologic Considerations for Quantitative 18F-FDG PET/CT Studies of Hepatic Glucose Metabolism in Healthy Subjects. AB - PET with the glucose analog (18)F-FDG is used to measure regional tissue metabolism of glucose. However, (18)F-FDG may have affinities different from those of glucose for plasma membrane transporters and intracellular enzymes; the lumped constant (LC) can be used to correct these differences kinetically. The aims of this study were to investigate the feasibility of measuring human hepatic glucose metabolism with dynamic (18)F-FDG PET/CT and to determine an operational LC for (18)F-FDG by comparison with (3)H-glucose measurements. METHODS: Eight healthy human subjects were included. In all studies, (18)F-FDG and (3)H-glucose were mixed in saline and coadministered. A 60-min dynamic PET recording of the liver was performed for 180 min with blood sampling from catheters in a hepatic vein and a radial artery (concentrations of (18)F-FDG and (3)H-glucose in blood). Hepatic blood flow was determined by indocyanine green infusion. First, 3 subjects underwent studies comparing bolus administration and constant-infusion administration of tracers during hyperinsulinemic-euglycemic clamping. Next, 5 subjects underwent studies comparing fasting and hyperinsulinemic-euglycemic clamping with tracer infusions. Splanchnic extraction fractions of (18)F-FDG (E*) and (3)H-glucose (E) were calculated from concentrations in blood, and the LC was calculated as ln(1 - E*)/ln(1 - E). Volumes of interest were drawn in the liver tissue, and hepatic metabolic clearance of (18)F-FDG (mL of blood/100 mL of liver tissue/min) was estimated. RESULTS: For bolus versus infusion, E* values were always negative when (18)F-FDG was administered as a bolus and were always positive when it was administered as an infusion. For fasting versus clamping, E* values were positive in 4 of 5 studies during fasting and were always positive during clamping. Negative extraction fractions were ascribed to the tracer distribution in the large volume of distribution in the prehepatic splanchnic bed. The LC ranged from 0.43 to 2.53, with no significant difference between fasting and clamping. CONCLUSION: The large volume of distribution of (18)F-FDG in the prehepatic splanchnic bed may complicate the analysis of dynamic PET data because it represents the mixed tracer input to the liver via the portal vein. Therefore, dynamic (18)F-FDG data for human hepatic glucose metabolism should be interpreted with caution, but constant tracer infusion seems to yield more robust results than bolus injection. PMID- 26159591 TI - Reply: Alzheimer Disease: Approaches to Early Diagnosis and High-Accuracy Imaging. PMID- 26159592 TI - 15-Year Experience of 18F-FDG PET Imaging in Response Assessment and Restaging After Definitive Treatment of Merkel Cell Carcinoma. AB - The objective of this study was to evaluate the utility of (18)F-FDG PET in restaging and response assessment of patients who underwent definitive treatment for Merkel cell carcinoma (MCC). METHODS: A retrospective review of patients undergoing (18)F-FDG PET imaging for MCC between January 1997 and October 2010 at the Peter MacCallum Cancer Centre with follow-up until February 2015 was performed. Data analysis was performed on patients who were treated definitively and underwent post-treatment PET imaging performed either as a restaging scan for ongoing monitoring, suspicion of recurrence, or assessment for suitability of salvage treatment or as response assessment within 1-6 mo of treatment. Management plans were recorded prospectively before (18)F-FDG PET imaging and compared with post-imaging management to assess the impact of the study as per our previously defined categories: high if the primary treatment modality or intent was changed and medium if the radiotherapy technique or dose was altered. In total, 62 patients were included in the analysis. Thirty-six patients underwent 53 restaging scans, and 37 patients underwent a response-assessment scan. The median follow-up of patients in the restaging group was 5.3 y (95% confidence interval [CI], 4.6-9.4), and it was 5.7 y (95% CI, 4.3-10.8) in the response-assessment group. RESULTS: Restaging (18)F-FDG PET scans had a high impact in 24 of 53 cases (45%) and a medium impact in 6 of 53 cases (11%). In the response-assessment group, 24 of 37 patients had a complete metabolic response (CMR). Patients without a CMR had a 15% 1-y overall survival (95% CI, 0.04-0.55). Those with a CMR had an 88% 2-y overall survival (95% CI, 0.75-1.00) and a 68% 5 y overall survival (95% CI, 0.49-0.95). The presence of a CMR (P < 0.001) and nodal involvement (P = 0.016) were statistically significant prognostic factors for overall survival. CONCLUSION: (18)F-FDG PET imaging had a high impact on restaging after definitive treatment in patients with MCC. Metabolic response was significantly associated with overall survival. (18)F-FDG PET may play an important role in ongoing post-treatment management of MCC. PMID- 26159597 TI - Racial/ethnic variations in the main and buffering effects of ethnic and nonethnic supports on depressive symptoms among five ethnic immigrant groups in Toronto. AB - OBJECTIVES: This study examined variations in the main and buffering effects of ethnic and nonethnic social support on depressive symptoms associated with discrimination among five immigrant groups in Toronto. DESIGN: Data were taken from the Toronto Study of Settlement and Health, a cross-sectional survey of adult immigrants from five ethnic communities (Vietnamese, Ethiopian, Iranian, Korean, and Irish) in Toronto. A total of 900 surveys were collected through face to-face interviews conducted between April and September 2001. RESULTS: Significant ethnic variations were observed in the effects of both ethnic and nonethnic social supports on discrimination-related depressive symptoms. Regarding the main effect, ethnic social support was significantly stronger for Iranian, Ethiopian, and Korean immigrants than for Irish immigrants. The benefits of nonethnic support were stronger for Iranian immigrants compared to the effect found in the Irish sample. With respect to stress-buffering or stress-moderating effects of social support, ethnic support was significant in all ethnic groups, except the Vietnamese group. Nonethnic support aggravated the negative impact of discrimination on depressive symptoms in the Irish group, but exerted a stress buffering effect in the Iranian group. CONCLUSIONS: Overall, social supports received from fellow ethnic group members had significant main effects (suppressing depressive symptoms) and stress-buffering effects and were most pronounced in the minority ethnic immigrant groups of Ethiopians, Koreans, and Iranians. The effects were least evident among the Vietnamese and Irish. Evidence for the stress-suppressing and stress-buffering role of cross-ethnic group supports was unclear, and even inverted among Irish immigrants. Empirical evidence from the current study seems to support the sociocultural similarity hypothesis of social support. PMID- 26159598 TI - Report on the EUROMAC McArdle Exercise Testing Workshop, Madrid, Spain, 11-12 July 2014. PMID- 26159599 TI - Early versus Delayed Therapy of Advanced Gastric Cancer Patients--Does It Make a Difference? AB - BACKGROUND: Nearly 50% of gastric cancer patients are diagnosed with advanced gastric cancer (AGC). Therapy is palliative but results in ill effects. The median overall survival (OS) of AGC patients is often <12 months. It is unclear if the early initiation of therapy in all AGC patients is beneficial. METHODS: A retrospective analysis of AGC patients in our database was carried out. The patients were divided into two groups: asymptomatic or symptomatic. We sought to assess whether the delay of systemic therapy was harmful in asymptomatic patients. RESULTS: A total of 135 patients were analyzed. Most patients were symptomatic (68%), males (67%), and had low ECOG scores (0-1; 85%). In univariate analyses, ECOG performance status 0 (p = 0.005), delayed initiation of therapy (p = 0.03), and lack of symptoms (p = 0.03) were associated with a longer OS. The multivariate model for OS identified only ECOG performance status as an independent prognosticator of longer OS (p = 0.02). Asymptomatic patients who had delayed (>= 4 weeks) systemic therapy had an OS rate of 77% at 1 year compared to 58% for patients treated within 4 weeks (p = 0.47). CONCLUSION: Symptomatic AGC patients had a poor outcome compared to asymptomatic AGC patients. Treatment delay in asymptomatic patients had no detrimental effect on OS, suggesting that the timing of therapy can be based on patient selection. PMID- 26159600 TI - Replication and contradiction of highly cited research papers in psychiatry: 10 year follow-up. AB - BACKGROUND: Contradictions and initial overestimates are not unusual among highly cited studies. However, this issue has not been researched in psychiatry. Aims: To assess how highly cited studies in psychiatry are replicated by subsequent studies. METHOD: We selected highly cited studies claiming effective psychiatric treatments in the years 2000 through 2002. For each of these studies we searched for subsequent studies with a better-controlled design, or with a similar design but a larger sample. RESULTS: Among 83 articles recommending effective interventions, 40 had not been subject to any attempt at replication, 16 were contradicted, 11 were found to have substantially smaller effects and only 16 were replicated. The standardised mean differences of the initial studies were overestimated by 132%. Studies with a total sample size of 100 or more tended to produce replicable results. CONCLUSIONS: Caution is needed when a study with a small sample size reports a large effect. PMID- 26159601 TI - Excess cause-specific mortality in in-patient-treated individuals with personality disorder: 25-year nationwide population-based study. AB - BACKGROUND: Although personality disorders are associated with increased overall mortality, less is known about cause of death and personality type. AIMS: To determine causes of mortality in ICD personality disorders. METHOD: Based on data from Swedish nationwide registers, individuals admitted to hospital with a primary diagnosis of personality disorder between 1987 and 2011 were followed with respect to mortality until 31 December 2011. Standardised mortality ratios (SMRs) with 95% confidence intervals and underlying causes of death were calculated. RESULTS: All-cause SMRs were increased, overall and in all clusters, for natural as well as unnatural causes of death. The overall SMR was 6.1 in women and 5.0 in men, as high as previously reported for anorexia nervosa, with higher rates in cluster B and mixed/other personality disorders. The SMR for suicide was 34.5 in women and 16.0 in men for cluster B disorders. Somatic and psychiatric comorbidity increased SMRs. CONCLUSIONS: The SMR was substantially increased for all personality disorder clusters. Thus, there was an increased premature mortality risk for all personality disorders, irrespective of category. PMID- 26159602 TI - Suicide by people in a community justice pathway: population-based nested case control study. AB - The elevated risk of suicide in prison and after release is a well-recognised and serious problem. Despite this, evidence concerning community-based offenders' suicide risk is sparse. We conducted a population-based nested case-control study of all people in a community justice pathway in England and Wales. Our data show 13% of general population suicides were in community justice pathways before death. Suicide risks were highest among individuals receiving police cautions, and those having recent, or impending prosecution for sexual offences. Findings have implications for the training and practice of clinicians identifying and assessing suicidality, and offering support to those at elevated risk. PMID- 26159603 TI - Antidepressant use in 27 European countries: associations with sociodemographic, cultural and economic factors. AB - BACKGROUND: Prescribing of antidepressants varies widely between European countries despite no evidence of difference in the prevalence of affective disorders. AIMS: To investigate associations between the use of antidepressants, country-level spending on healthcare and country-level attitudes towards mental health problems. METHOD: We used Eurobarometer 2010, a large general population survey from 27 European countries, to measure antidepressant use and regularity of use. We then analysed the associations with country-level spending on healthcare and country-level attitudes towards mental health problems. RESULTS: Higher country spending on healthcare was strongly associated with regular use of antidepressants. Beliefs that mentally ill people are 'dangerous' were associated with higher use, and beliefs that they 'never recover' or 'have themselves to blame' were associated with lower and less regular use of antidepressants. CONCLUSIONS: Contextual factors, such as healthcare spending and public attitudes towards mental illness, may partly explain variations in antidepressant use and regular use of these medications. PMID- 26159604 TI - Abnormal brain activation in excoriation (skin-picking) disorder: evidence from an executive planning fMRI study. AB - BACKGROUND: Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. AIMS: To probe the function of fronto-striatal circuitry in SPD. METHOD: Eighteen participants with SPD and 15 matched healthy controls undertook an executive planning task (Tower of London) during functional magnetic resonance imaging (fMRI). Activation during planning was compared between groups using region of interest and whole-brain permutation cluster approaches. RESULTS: The SPD group exhibited significant functional underactivation in a cluster encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. CONCLUSIONS: Abnormalities of neural regions involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive-compulsive spectrum disorders. PMID- 26159605 TI - Sleep and Cognitive Decline: A Strong Bidirectional Relationship. It Is Time for Specific Recommendations on Routine Assessment and the Management of Sleep Disorders in Patients with Mild Cognitive Impairment and Dementia. AB - BACKGROUND: Sleep disturbances and disruption of the neural regulation of the sleep-wake rhythm appear to be involved in the cellular and molecular mechanisms of cognitive decline. Although sleep problems are highly prevalent in mild cognitive impairment (MCI) and many types of dementia, they have not been systematically investigated in the clinical setting and are often only investigated by sleep specialists upon individual request. SUMMARY: This review discusses sleep disorders in the context of cognitive decline and provides an overview of the clinical diagnosis and management of these disorders in patients with dementia and MCI. Key Messages: Sleep disorders are largely underestimated and do not receive sufficient attention in the global management of dementia patients. Sleep disturbances have a significant impact on cognitive and physical functions in individuals with cognitive decline and may be associated with important psychological distress and depression. They are positively associated with the severity of behavioral problems and cognitive impairment. CLINICAL IMPLICATIONS: The recent recommendations by the Sleep Study Group of the Italian Dementia Research Association can be used as a guideline for the clinical assessment and management of sleep disorders in MCI and dementia patients. Sleep disorders should be carefully investigated using an in-depth sleep history, physical examination, questionnaires and clinical scales and should be validated with the support of a direct caregiver. The recommendations for older adults can be used as a framework to guide the diagnosis and treatment of sleep disorders in individuals with dementia and MCI. The management strategy should be based on the choice of different treatments for each sleep problem present in the same patient, while avoiding adverse interactions between treatments. PMID- 26159606 TI - Mutations in LRRK2 potentiate age-related impairment of autophagic flux. AB - Autophagy is thought to play a pivotal role in the pathophysiology of Parkinson's disease, but little is known about how genes linked to PD affect autophagy in the context of aging. We generated lines of C. elegans expressing reporters for the autophagosome and lysosome expressed only in dopaminergic neurons, and examined autophagy throughout the lifespan in nematode lines expressing LRRK2 and alpha synuclein. Dopamine neurons exhibit a progressive loss of autophagic function with aging. G2019S LRRK2 inhibited autophagy and accelerated the age-related loss of autophagic function, while WT LRRK2 improved autophagy throughout the life span. Expressing alpha-synuclein with G2019S or WT LRRK2 caused age-related synergistic inhibition of autophagy and increase in degeneration of dopaminergic neurons. The presence of alpha-synuclein particularly accentuated age-related inhibition of autophagy by G2019S LRRK2. This work indicates that LRRK2 exhibits a selective, age-linked deleterious interaction with alpha-synuclein that promotes neurodegeneration. PMID- 26159607 TI - Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs. AB - Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2 specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs. PMID- 26159608 TI - Impact of urgent coronary angiography on mid-term clinical outcome of comatose out-of-hospital cardiac arrest survivors presenting without ST-segment elevation. AB - BACKGROUND: Timing of coronary angiography (CAG) is still controversial in the out-of-hospital cardiac arrest survivors who present without ST-segment elevation. METHODS AND RESULTS: We analysed a prospective registry of 158 comatose survivors of out-of-hospital cardiac arrest. For further analysis, we included 99 patients without ST-segment elevation on the initial electrocardiogram. All patients underwent temperature management. Urgent CAG (<2h from admission) was performed in 25% of the patients. A definite cause of the cardiac arrest could be identified during the index hospitalization in 82 patients: 36 had a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and 46 had a non-ACS diagnosis. Eighty-seven patients (88%) survived the index hospitalization and 65 (66%) were alive at six months. A favourable neurological status (cerebral performance category <= 2) was observed in 56% of the patients at discharge and in 56% after six months of follow-up. Neither the survival nor the neurological outcome differed between the patients in whom the CAG was performed urgently upon the admission and the patients in whom the CAG was initially not performed, regardless of the aetiology of the cardiac arrest. On the other hand, performing an urgent CAG was safe and it did not prolong the average time to achieve an effective hypothermia. CONCLUSIONS: Performing an urgent CAG in comatose cardiac arrest survivors without ST-segment elevation was not associated with better clinical and neurological outcome as compared to the initially conservative approach. PMID- 26159610 TI - Electrocardiographic findings of intracranial haemorrhage as a cause of out-of hospital cardiac arrest. PMID- 26159609 TI - Impact of time to return of spontaneous circulation on neuroprotective effect of targeted temperature management at 33 or 36 degrees in comatose survivors of out of hospital cardiac arrest. AB - AIM: Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33 degrees C over 36 degrees C on the prognostic importance of time to ROSC. METHODS: In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days. RESULTS: Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM. CONCLUSION: Time to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33 degrees C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36 degrees C. PMID- 26159611 TI - Cooling rate for triage decisions should exclude post-extrication cooling in avalanche victims. PMID- 26159612 TI - Neuroprognostication following out of hospital cardiac arrest--A retrospective study of departmental practice. PMID- 26159613 TI - Cerebral oximetry and return of spontaneous circulation after cardiac arrest: A systematic review and meta-analysis. AB - AIM: The prediction of return of spontaneous circulation (ROSC) during resuscitation of patients suffering of cardiac arrest (CA) is particularly challenging. Regional cerebral oxygen saturation (rSO2) monitoring through near infrared spectrometry is feasible during CA and could provide guidance during resuscitation. METHODS: We conducted a systematic review and meta-analysis on the value of rSO2 in predicting ROSC both after in-hospital (IH) or out-of-hospital (OH) CA. Our search included MEDLINE (PubMed) and EMBASE, from inception until April 4th, 2015. We included studies reporting values of rSO2 at the beginning of and/or during resuscitation, according to the achievement of ROSC. RESULTS: A total of nine studies with 315 patients (119 achieving ROSC, 37.7%) were included in the meta-analysis. The majority of those patients had an OHCA (n=225, 71.5%; IHCA: n=90, 28.5%). There was a significant association between higher values of rSO2 and ROSC, both in the overall calculation (standardized mean difference, SMD -1.03; 95%CI -1.39,-0.67; p<0.001), and in the subgroups analyses (rSO2 at the beginning of resuscitation: SMD -0.79; 95%CI -1.29,-0.30; p=0.002; averaged rSO2 value during resuscitation: SMD -1.28; 95%CI -1.74,-0.83; p<0.001). CONCLUSIONS: Higher initial and average regional cerebral oxygen saturation values are both associated with greater chances of achieving ROSC in patients suffering of CA. A note of caution should be made in interpreting these results due to the small number of patients and the heterogeneity in study design: larger studies are needed to clinically validate cut-offs for guiding cardiopulmonary resuscitation. PMID- 26159614 TI - Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. AB - Agouti-related-peptide (AgRP) neurons-interoceptive neurons in the arcuate nucleus of the hypothalamus (ARC)-are both necessary and sufficient for driving feeding behavior. To better understand the functional roles of AgRP neurons, we performed optetrode electrophysiological recordings from AgRP neurons in awake, behaving AgRP-IRES-Cre mice. In free-feeding mice, we observed a fivefold increase in AgRP neuron firing with mounting caloric deficit in afternoon vs morning recordings. In food-restricted mice, as food became available, AgRP neuron firing dropped, yet remained elevated as compared to firing in sated mice. The rapid drop in spiking activity of AgRP neurons at meal onset may reflect a termination of the drive to find food, while residual, persistent spiking may reflect a sustained drive to consume food. Moreover, nearby neurons inhibited by AgRP neuron photostimulation, likely including satiety-promoting pro opiomelanocortin (POMC) neurons, demonstrated opposite changes in spiking. Finally, firing of ARC neurons was also rapidly modulated within seconds of individual licks for liquid food. These findings suggest novel roles for antagonistic AgRP and POMC neurons in the regulation of feeding behaviors across multiple timescales. PMID- 26159616 TI - The changing role of a Vaidya (non-codified traditional doctor) in the community health of Kerala, Southern India: comparison of treatment-seeking behaviours between the Vaidya's patients and community members. AB - BACKGROUND: This study aimed at exploring the roles of a Vaidya - an uncodified traditional doctor - in a community in Kerala State, India. Special attention was paid to the characteristics of the Vaidya's patients in comparison with the treatment-seeking behaviour of the community members. METHODS: Both qualitative and quantitative data about the Vaidya, 97 of his patients, and 31 community members were gathered via participatory fieldwork and open-ended interviews. RESULTS: It was found that the community members seldom consulted the Vaidya who lived in their community; thus, the role of the Vaidya as the community's primary health care provider had nearly disappeared. Nonetheless, the Vaidya was deeply respected as one of the community's leaders by its members because of the spiritual and financial support he provided to them. On the other hand, a number of patients visited the Vaidya from outside the village, which implied that the Vaidya played a new role under the changes caused by medical pluralism. Even a codified traditional medicine, Ayurveda, was less popular among the community members. These findings were interesting, because while the traditional Indian medical system has been becoming popular and common in other societies, such as European societies, as an alternative medicine, the traditional medical system was becoming less important in the rural Indian context. CONCLUSION: It is thus concluded that the medical practice has changed depending on its cultural and social contexts, even though its medicinal effects had been proven by scientific survey. PMID- 26159615 TI - Slit2 as a beta-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation. AB - Neuromuscular junction formation requires proper interaction between motoneurons and muscle cells. beta-Catenin (Ctnnb1) in muscle is critical for motoneuron differentiation; however, little is known about the relevant retrograde signal. In this paper, we dissected which functions of muscle Ctnnb1 are critical by an in vivo transgenic approach. We show that Ctnnb1 mutant without the transactivation domain was unable to rescue presynaptic deficits of Ctnnb1 mutation, indicating the involvement of transcription regulation. On the other hand, the cell-adhesion function of Ctnnb1 is dispensable. We screened for proteins that may serve as a Ctnnb1-directed retrograde factor and identified Slit2. Transgenic expression of Slit2 specifically in the muscle was able to diminish presynaptic deficits by Ctnnb1 mutation in mice. Slit2 immobilized on beads was able to induce synaptophysin puncta in axons of spinal cord explants. Together, these observations suggest that Slit2 serves as a factor utilized by muscle Ctnnb1 to direct presynaptic differentiation. PMID- 26159618 TI - MiR-1271 Inhibits Cell Proliferation, Invasion and EMT in Gastric Cancer by Targeting FOXQ1. AB - BACKGROUND/AIMS: FOXQ1 overexpression has been reported to enhance tumor growth and invasion. However, the biological function of FOXQ1 and the mechanism underlying its upregulation in gastric cancer (GC) remain unknown. METHODS: QPCR was used to detect the expression of miR-1271 and FOXQ1 in specimens from GC patients. FOXQ1-siRNA, and miR- 1271 mimics and inhibitor were transfected into human MGC-803 and SGC-7901 cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. Markers of epithelial-mesenchymal transition (EMT) were detected by western blot analysis. RESULTS: MiR-1271 was downregulated in both GC tissues and GC cell lines. The expression of miR-1271 was inversely correlated with tumor size (P = 0.017), tumor stage (P = 0.035), lymph node metastasis (P = 0.018), and TNM stage (P = 0.025). Ectopic expression of miR-1271 dramatically suppressed GC cell proliferation, invasion, and EMT. Furthermore, FOXQ1 was identified as a direct target of miR-1271. Knockdown of FOXQ1 inhibited GC cell malignant behavior, whereas FOXQ1 overexpression partially restored the suppression effects of miR-1271. Additionally, miR-1271 expression was negatively correlated with FOXQ1 in GC tissues. CONCLUSIONS: MiR-1271 inhibits cell proliferation, invasion, and EMT in GC by directly suppressing FOXQ1 expression. PMID- 26159617 TI - Molecular basis of hERG potassium channel blockade by the class Ic antiarrhythmic flecainide. AB - The class Ic antiarrhythmic drug flecainide inhibits KCNH2-encoded "hERG" potassium channels at clinically relevant concentrations. The aim of this study was to elucidate the underlying molecular basis of this action. Patch clamp recordings of hERG current (IhERG) were made from hERG expressing cells at 37 degrees C. Wild-type (WT) IhERG was inhibited with an IC50 of 1.49MUM and this was not significantly altered by reversing the direction of K(+) flux or raising external [K(+)]. The use of charged and uncharged flecainide analogues showed that the charged form of the drug accesses the channel from the cell interior to produce block. Promotion of WT IhERG inactivation slowed recovery from inhibition, whilst the N588K and S631A attenuated-inactivation mutants exhibited IC50 values 4-5 fold that of WT IhERG. The use of pore-helix/selectivity filter (T623A, S624A V625A) and S6 helix (G648A, Y652A, F656A) mutations showed <10-fold shifts in IC50 for all but V625A and F656A, which respectively exhibited IC50s 27 fold and 142-fold their WT controls. Docking simulations using a MthK-based homology model suggested an allosteric effect of V625A, since in low energy conformations flecainide lay too low in the pore to interact directly with that residue. On the other hand, the molecule could readily form pi-pi stacking interactions with aromatic residues and particularly with F656. We conclude that flecainide accesses the hERG channel from the cell interior on channel gating, binding low in the inner cavity, with the S6 F656 residue acting as a principal binding determinant. PMID- 26159619 TI - Genome-wide analysis of signatures of selection in populations of African honey bees (Apis mellifera) using new web-based tools. AB - BACKGROUND: With the development of inexpensive, high-throughput sequencing technologies, it has become feasible to examine questions related to population genetics and molecular evolution of non-model species in their ecological contexts on a genome-wide scale. Here, we employed a newly developed suite of integrated, web-based programs to examine population dynamics and signatures of selection across the genome using several well-established tests, including F ST, pN/pS, and McDonald-Kreitman. We applied these techniques to study populations of honey bees (Apis mellifera) in East Africa. In Kenya, there are several described A. mellifera subspecies, which are thought to be localized to distinct ecological regions. RESULTS: We performed whole genome sequencing of 11 worker honey bees from apiaries distributed throughout Kenya and identified 3.6 million putative single-nucleotide polymorphisms. The dense coverage allowed us to apply several computational procedures to study population structure and the evolutionary relationships among the populations, and to detect signs of adaptive evolution across the genome. While there is considerable gene flow among the sampled populations, there are clear distinctions between populations from the northern desert region and those from the temperate, savannah region. We identified several genes showing population genetic patterns consistent with positive selection within African bee populations, and between these populations and European A. mellifera or Asian Apis florea. CONCLUSIONS: These results lay the groundwork for future studies of adaptive ecological evolution in honey bees, and demonstrate the use of new, freely available web-based tools and workflows ( http://usegalaxy.org/r/kenyanbee ) that can be applied to any model system with genomic information. PMID- 26159621 TI - P-glycoprotein expression and amyloid accumulation in human aging and Alzheimer's disease: preliminary observations. AB - P-glycoprotein (P-gp), part of the blood-brain barrier, limits drug access to the brain and is the target for therapies designed to improve drug penetration. P-gp also extrudes brain amyloid-beta (Abeta). Accumulation of Abeta is a hallmark of Alzheimer's disease (AD). Abeta accumulates in normal aging and in AD primarily due to decreased Abeta clearance. This is a preliminary report on the relative protein and messenger RNA expression of P-gp in human brains, ages 20-100 years, including AD subjects. In these preliminary studies, cortical endothelial P-gp expression decreased in AD compared with controls (p < 0.001). Trends in P-gp expression in human aging are similar to aging rats. Microvessel P-gp messenger RNA remained unchanged with aging and AD. Abeta plaques were found in 42.8% of normal subjects (54.5% of those older than 50 years). A qualitative analysis showed that P-gp expression is lower than the group mean in subjects older than 75 years but increased if younger. Decreased P-gp expression may be related to Abeta plaques in aging and AD. Downregulating P-gp to allow pharmaceuticals into the central nervous system may increase Abeta accumulation. PMID- 26159620 TI - Difficult healthcare transitions: Ethical analysis and policy recommendations for unrepresented patients. AB - BACKGROUND: In Ontario, Canada, patients who lack decision-making capacity and have no family or friends to act as substitute decision-makers currently rely on the Office of the Public Guardian and Trustee to consent to long-term care (nursing home) placement, but they have no legal representative for other placement decisions. OBJECTIVES: We highlight the current gap in legislation for difficult transition cases involving unrepresented patients and provide a novel framework for who ought to assist with making these decisions and how these decisions ought to be made. RESEARCH DESIGN: This paper considers models advanced by Volpe and Steinman with regard to who ought to make placement decisions for unrepresented patients, as well as current ethical models for analyzing how these decisions should be made. PARTICIPANTS AND RESEARCH CONTEXT: We describe an anonymized healthcare transition case to illustrate the fact that there is no legally recognized decision-maker for placement destinations other than long-term care facilities and to show how this impacts all stakeholders. ETHICAL CONSIDERATIONS: The case provided is an anonymized vignette representing a typical transition case involving an unrepresented patient. FINDINGS: As a result of a gap in provincial legislation, healthcare providers usually determine the appropriate placement destination without a clear framework to guide the process and this can cause significant moral distress. DISCUSSION: We argue for a team decision-making approach in the short term, and a legislative change in the long term, to respect the patient voice, evaluate benefit and risk, enhance collaboration between healthcare providers and patients, and promote social justice. We believe that our approach, which draws upon the strengths of interprofessional teams, will be of interest to all who are concerned with the welfare and ethical treatment of the patients for whom they care. CONCLUSIONS: One of the main strengths of our recommendation is that it provides all members of the healthcare team (including nurses, social workers, therapists, and others) an increased opportunity to advocate on behalf of unrepresented patients. PMID- 26159622 TI - Possible Impact of Yearly Childhood Vaccination With Trivalent Inactivated Influenza Vaccine (TIV) on the Immune Response to the Pandemic Strain H1N1. AB - BACKGROUND: Annual vaccination of children against seasonal influenza with trivalent inactivated influenza vaccine (TIV) has shown to be beneficial. However, this yearly practice may have unintended effect. Studies have shown that infection with wild type influenza A viruses can stimulate protective heterotypic immunity against unrelated or new influenza subtypes. We hypothesized that a consequence of yearly TIV vaccination is lack of induction of heterotypic immunity against the recent H1N1 pandemic. METHODS: This was a retrospective case control study. We reviewed the medical records of polymerase chain reaction confirmed cases of 2009 H1N1 influenza infection in children 6 months to 18 years and a matched control group seen during the pandemic. RESULTS: We identified 353 polymerase chain reaction-confirmed H1N1 cases and 396 matching control subjects. Among the H1N1 group, 202/353 (57%) cases received a total of 477 doses of seasonal TIV compared with 218/396 (55%) in the control group who received a total of 435 doses. Seasonal TIV uptake was significantly higher in the H1N1 group 477/548 (87%) than in the control group, 435/532 (81%) (P = .017). CONCLUSION: Seasonal TIV uptake was significantly higher in H1N1-infected group. The finding suggests that the practice of yearly vaccination with TIV might have negatively affected the immune response against the novel pandemic H1N1 strain. Given the rarity of pandemic novel influenza viruses, and the high predictability of seasonal influenza occurrence, the practice of yearly influenza vaccination should be continued. However, the use of live attenuated intranasal vaccine, as opposed to TIV, may allow for the desirable development of a vigorous heterotypic immune response against future pandemics. PMID- 26159623 TI - A single sym plasmid type predominates across diverse chromosomal lineages of Cupriavidus nodule symbionts. AB - Cupriavidus nodule symbionts from Mimosa host legumes indigenous to five locations around the Caribbean region were analyzed by sequencing portions of five chromosomal housekeeping loci and five sym plasmid loci in 80 isolates. Nodule symbionts did not form a single clade separated from non-symbiotic reference strains of Cupriavidus and Ralstonia, implying that either convergent losses or independent gains of the trait of legume symbiosis have taken place. Chromosomal genes exhibited significantly higher nucleotide polymorphism and haplotype diversity than sym plasmid loci. A single derived sym plasmid haplotype (A1) was found to predominate in four of the populations, and was shared by multiple housekeeping gene clades. This suggests that one sym plasmid variant has recently spread geographically and has been acquired by diverse chromosomal lineages within the region. Inoculation of two Mimosa host species indicated that strains carrying the predominant A1 haplotype ranked either first or second among the five major sym plasmid haplotype groups with respect to plant growth enhancement. Symbiotic outcomes also varied greatly among chromosomally diverse strains that all shared the A1 haplotype. Thus, chromosomal as well as sym plasmid variants likely contribute to differential interactions with Mimosa host species. PMID- 26159624 TI - Evaluating the efficacy of a web-based self-help intervention with and without chat counseling in reducing the cocaine use of problematic cocaine users: the study protocol of a pragmatic three-arm randomized controlled trial. AB - BACKGROUND: Web-based self-help interventions that aim to reduce problematic substance use are able to reach "hidden" consumer groups in the general population who often fear stigmatization and thus avoid institutional addiction treatment. In Western European countries, including Switzerland, cocaine is the most widely used psychoactive substance after alcohol, tobacco, and cannabis. Although approximately one in six users develop serious problems of dependency, only a minority seeks help from psychiatrists or in outpatient counseling centers or psychiatric hospitals. Offering web-based therapy treatment may potentially reach users who hesitate to approach institutional treatment services and help them reduce their cocaine use before they get into more serious trouble. METHODS/DESIGN: The study will use a three-arm randomized controlled trial (RCT) design to test the efficacy of a web-based self-help intervention with or without guided chat counseling compared with that of a waiting list control condition in reducing or stopping cocaine use. The primary outcome measure will be the weekly quantity of cocaine used. Secondary outcome measures will include the number of cocaine use days in the past 30 days, the severity of cocaine dependence, the use of alcohol, tobacco, and/or other illicit drugs, changes in mental health symptoms, and treatment retention. The self-help intervention will consist of eight modules that are designed to reduce cocaine use and depression symptoms. These modules are based on the principles of Motivational Enhancement Therapy and Cognitive Behavioral Therapy, such as Behavioral Self-Management. The three individual chat therapy sessions will be based on the same therapy approaches and will be tailored to participants' self-help data and aim to assist the reinstatement of social rewards and the improvement of social support and relationships. DISCUSSION: This study will be the first RCT to test the effectiveness of a web-based self-help intervention in combination with or without chat counseling in reducing cocaine use. The expected findings will contribute substantial knowledge that may help design effective guided and unguided web-based treatment for cocaine users. Moreover, the study will elucidate to what extent a therapeutic alliance with cocaine users can be established in a guided Internet-delivered setting. Additionally, the present study will investigate changes in social support with specific guided therapy interventions that aim to ameliorate social support and social perceptions and compare these changes with those in an unguided self-help intervention TRIAL REGISTRATION: Current Controlled Trials ISRCTN12205466 . Registered 24 February 2015. PMID- 26159625 TI - Bing-Neel syndrome: Two unexpected cases and a review of the literature. AB - Waldenstrom macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the proliferation of small B-lymphocytes in the bone marrow that produce monoclonal immunoglobulin M (IgM). We describe two patients with WM who presented with neurological symptoms due to infiltration of lymphoplasmacytoid tumor cells in the central nervous system, a condition known as Bing-Neel syndrome. A literature review revealed that this syndrome is rare and commonly missed in clinical practice due to its variable presentation and a lack of awareness or knowledge. Brain and spinal magnetic resonance imaging may show a focal mass or diffuse infiltration. The diagnosis of Bing-Neel syndrome requires proof of IgM or lymphoplasmacytoid cells in cerebrospinal fluid or in a brain biopsy. Treatment with intravenous and/or intrathecal chemotherapy and cranial radiotherapy is described in literature with generally poor outcome, although a combination of these therapies seems to improve outcome. Nevertheless, insufficient data are currently available to make general treatment recommendations. PMID- 26159626 TI - Do executive dysfunction and freezing of gait in Parkinson's disease share the same neuroanatomical correlates? AB - Current hypotheses postulate a relationship between executive dysfunction and freezing of gait (FOG) in Parkinson's disease (PD). Hitherto, most evidence comes from entirely clinical approaches, while knowledge about this relationship on the morphological level is sparse. The aim of this study was therefore to assess the overlap of gray matter atrophy associated with FOG and executive dysfunction in PD. We included 18 PD patients with FOG and 20 without FOG in our analysis. A voxel-based morphometry approach was used to reveal voxel clusters in the gray matter which were associated with FOG and executive dysfunction as measured by the Frontal Assessment Battery, respectively. Conjunction analysis was applied to detect overlaps of the associated patterns. FOG correlated with different cortical clusters in the frontal and parietal lobes, whereas those associated with the FAB scores were, although widespread, widely confined to the frontal lobe. Conjunction analysis revealed a significant cluster of gray matter loss in the right dorsolateral prefrontal cortex. We could show that the patterns of neurodegeneration associated with FOG and executive dysfunction (as measured by the FAB) share atrophic changes in the same cortical areas. However, there is also a considerable number of cortical areas where neurodegenerative changes are only unique for either sign. Particularly, the involvement of parietal lobe areas seems to be more specific for FOG. PMID- 26159627 TI - Childhood Adversity Among Institutionalized Male Juvenile Offenders and Other High-Risk Groups Without Offense Records in Portugal. AB - The literature has shown that delinquent adolescents report high rates of childhood adversity and family dysfunction. However, it is important to know both the degree of adversity among delinquent adolescents in comparison with other high-risk samples and the contribution of each single form of adversity to this comparison. The purpose of this study was to evaluate childhood adversity, psychopathology, and risk behaviors among 4 high-risk groups, including incarcerated delinquent youths. The participants were 120 male youths between 13 and 19 years old (M = 16.18, SD = 1.26), including 30 youths who were arrested and held in detention centers as a consequence of violent crimes; 30 youths who were identified by Child Protective Services (CPS) and remained with their families; 30 youths who were identified by CPS, removed from their homes, and placed in child and youth residential care; and 30 youths who were randomly selected from schools. The incarcerated youths reported significantly more adversity, global psychopathology, and global index of risk behaviors. When considering each risk behavior, the incarcerated youths reported higher percentages of alcohol abuse, drug use, early smoking initiation, physical assault, carrying weapons, early initiation of sexual intercourse, sexual intercourse under the influence of drugs, and sexual intercourse without condom use. The logistic regression analyses showed that only emotional neglect was significantly associated with delinquency. This study suggests that delinquent youths are exposed to a great magnitude of adversities in childhood, with emotional neglect as an independent risk factor for delinquency. In addition, these youths have higher rates of psychopathology and risk behaviors compared to other high-risk samples. PMID- 26159628 TI - Comparison of three media for transport and storage of the samples collected for detection of avian influenza virus. AB - Detection of avian influenza viruses (AIVs) is important for diagnosis, surveillance and control of avian influenza which is of great economic and public health significance. Proper transport and storage of samples is critical for the detection when the samples cannot be detected immediately. As recommended by some international or national authoritative entities and some publications, phosphate buffered saline (PBS), PBS-glycerol and brain heart infusion broth (BHIB) are frequently used for transport and storage of the samples collected for detection of AIVs worldwide. In this study, we compared these three media for transport and storage of simulated and authentic swab and feces samples collected for detection of AIVs using virus isolation and reverse transcription-PCR. The results suggest that PBS-glycerol is superior to PBS and BHIB as the sample transport and storage media. The results also suggest that the samples collected for detection of AIVs should be detected as soon as possible because the virus concentration of the samples may decline rapidly during storage within days at 4 or -20 degrees C. PMID- 26159629 TI - Dengue fever in Czech travellers: A 10-year retrospective study in a tertiary care centre. AB - BACKGROUND: Dengue fever is a frequent cause of morbidity in travellers. The objective was to describe the epidemiological and clinical characteristics of dengue fever in Czech travellers. METHOD: This descriptive study includes patients with acute dengue fever diagnosed at Hospital Na Bulovce during 2004 2013. Data were collected and analysed retrospectively. RESULTS: A total of 132 patients (83 males and 49 females) of median age 33 years (IQR 29-40) were included. Diagnosis was established by NS1 antigen detection in 87/107 cases (81.3%) and/or RT-PCR in 50/72 (69.4%) and by serology in 25 cases (18.9%). Dengue was acquired in South-East Asia in 69 cases (52.3%), followed by South Asia (48 cases; 36.3%), Latin America (14; 10.6%) and Sub-Saharan Africa (1; 0.8%). The most frequent symptoms included fever, rash and headache. Initial leukocyte and lymphocyte counts were lower in patients who presented in the early phase (0-4 days), however, platelet count was lower and AST, ALT and LDH activity higher in patients with a longer symptoms duration (>=5 days). The clinical course was mostly uncomplicated. CONCLUSIONS: Dengue fever is becoming a frequent cause of fever in Czech travellers. Clinicians should be familiar with the typical clinical findings and novel diagnostic methods. PMID- 26159630 TI - Risk factors and clinical implication of superimposed Campylobacter jejuni infection in patients with underlying ulcerative colitis. AB - BACKGROUND AND AIMS: Superimposed Campylobacter jejuni infection (CJI) has been described in patients with ulcerative colitis (UC). Its risk factors and impact on the disease course of UC are not known. Our aims were to evaluate the risk factors for CJI in UC patients and the impact of the bacterial infection on outcomes of UC. METHODS: Out of a total of 918 UC patients tested, 21 (2.3%) of patients were found to be positive for CJI (the study group). The control group comprised 84 age-matched UC patients who had tested negative for CJI. Risk factors for CJI and UC-related outcomes at 1 year after diagnosis of CJI were compared between the two groups. RESULTS: Ten patients (47.6%) with CJI required hospital admission at the time of diagnosis, including eight for the management of "UC flare". Treatment with antibiotics resulted in improvement in symptoms in 13 patients (61.9%). On multivariate analysis, hospital admission in the preceding year was found to be an independent risk factor for CJI [odds ratio (OR): 3.9; 95% confidence interval (CI): 1.1-14.1] and there was a trend for chronic liver disease as a strong risk factor (OR: 5.0; 95% CI: 0.9-28.3). At 1 year follow up, there was a trend for higher rates of UC-related colectomy (28.8% vs. 14.3%; P = 0.11), and mortality (9.5% vs. 1.2%; P = 0.096) in the study group. CONCLUSION: Recent hospitalization within 1 year was found to be associated with increased risk for CJI in UC patients. There was a trend for worse clinical outcomes of UC with in patients with superimposed CJI, which was frequently associated with UC flare requiring hospital admission. PMID- 26159631 TI - Knowledge about non-invasive diagnostic tests for varices in liver cirrhosis: A questionnaire survey to the Gastroenterology Branch of the Liaoning Medical Association, China. AB - BACKGROUND AND AIMS: Due to the invasiveness of upper gastrointestinal endoscopy, non-invasive diagnostic tests for varices in liver cirrhosis have been widely established by numerous studies. A questionnaire survey, which was aimed at understanding the current knowledge about non-invasive diagnostic tests for varices in liver cirrhosis, was distributed among the members of Gastroenterology Branch of the Liaoning Medical Association. METHODS: A questionnaire assessing the knowledge about non-invasive diagnostic tests for varices was sent to 42 members who participated in the entire ninth committee. They were from 33 hospitals in 13 cities of Liaoning Province, China. RESULTS: Overall, 97.6% (41/42) of participants responded to the questionnaire. A majority of participants were chief physicians (85.4%), had >20 years of experience in clinical work of digestive diseases (80.5%) and worked at tertiary hospitals (97.6%). In 46.3% of participants' departments, there were >200 patients with liver cirrhosis and gastroesophageal varices admitted every year. In 90.2% of participants' departments, upper gastrointestinal endoscopy was regularly employed for the diagnosis of gastroesophageal varices. Only six (15%) participants often used non-invasive diagnostic tests for varices in clinical practice. Thirty (75%) participants knew at least one non-invasive diagnostic test for varices. The knowledge of at least one non-invasive diagnostic test was significantly associated with the number of cirrhotic patients with varices (P = 0.038) or the regular use of gastrointestinal endoscopy to diagnose varices (P = 0.022). CONCLUSIONS: This questionnaire survey suggested that non-invasive diagnostic tests for varices in liver cirrhosis were rarely or never used in clinical practices in Liaoning Province, China. Reliable, non-invasive indexes should be further explored in a well-designed multi-center observational study. PMID- 26159632 TI - Beyond conventional routes, an unprecedented metal-free chemoselective synthesis of anthranilate esters via a multicomponent reaction (MCR) strategy. AB - A hitherto unreported route for the synthesis of anthranilate esters is demonstrated using 2-nitrobenzaldehyde, malonitrile and an alcohol or amine via a metal and oxidant free multicomponent reaction (MCR) strategy. This process simultaneously installs an ester and urea or urethane functionality via CO and CN bond formations via concurrent oxidation of the aldehyde group and reduction of the nitro group involving an intramolecular redox process. PMID- 26159633 TI - Social Media Use in Chronic Disease: A Systematic Review and Novel Taxonomy. AB - PURPOSE: The purpose of this study is to evaluate clinical outcomes from applications of contemporary social media in chronic disease; to develop a conceptual taxonomy to categorize, summarize, and then analyze the current evidence base; and to suggest a framework for future studies on this topic. METHODS: We performed a systematic review of MEDLINE via PubMed (January 2000 to January 2015) of studies reporting clinical outcomes on leading contemporary social media (ie, Facebook, Twitter, Wikipedia, YouTube) use in 10 chronic diseases. Two reviewers independently performed data extraction and quality assessment; characterization of study outcomes as positive, negative, neutral, or undefined impact; and inductive, thematic analysis to develop our taxonomy. RESULTS: Of 378 citations identified, 42 studies examining the use of Facebook (n = 16), blogs (n = 13), Twitter (n = 8), wikis (n = 5), and YouTube (n = 4) on outcomes in cancer (n = 14), depression (n = 13), obesity (n = 9), diabetes (n = 4), heart disease (n = 3), stroke (n = 2), and chronic lower respiratory tract infection (n = 1) were included. Studies were classified as support (n = 16), patient education (n = 10), disease modification (n = 6), disease management (n = 5), and diagnosis (n = 5) within our taxonomy. The overall impact of social media on chronic disease was variable, with 48% of studies indicating benefit, 45% neutral or undefined, and 7% suggesting harm. Among studies that showed benefit, 85% used either Facebook or blogs, and 40% were based within the domain of support. CONCLUSIONS: Using social media to provide social, emotional, or experiential support in chronic disease, especially with Facebook and blogs, appears most likely to improve patient care. PMID- 26159634 TI - Nutritional, Physical, Cognitive, and Combination Interventions and Frailty Reversal Among Older Adults: A Randomized Controlled Trial. AB - BACKGROUND: It is important to establish whether frailty among older individuals is reversible with nutritional, physical, or cognitive interventions, singly or in combination. We compared the effects of 6-month-duration interventions with nutritional supplementation, physical training, cognitive training, and combination treatment vs control in reducing frailty among community-dwelling prefrail and frail older persons. METHODS: We conducted a parallel group, randomized controlled trial in community-living prefrail and frail old adults in Singapore. The participants' mean age was 70.0 years, and 61.4% (n = 151) were female. Five different 6-month interventions included nutritional supplementation (n = 49), cognitive training (n = 50), physical training (n = 48), combination treatment (n = 49), and usual care control (n = 50). Frailty score, body mass index, knee extension strength, gait speed, energy/vitality, and physical activity levels and secondary outcomes (activities of daily living dependency, hospitalization, and falls) were assessed at 0 months, 3 months, 6 months, and 12 months. RESULTS: Frailty score and status over 12 months were reduced in all groups, including control (15%), but were significantly higher (35.6% to 47.8%) in the nutritional (odds ratio [OR] 2.98), cognition (OR 2.89), and physical (OR 4.05) and combination (OR 5.00) intervention groups. Beneficial effects were observed at 3 months and 6 months, and persisted at 12 months. Improvements in physical frailty domains (associated with interventions) were most evident for knee strength (physical, cognitive, and combination treatment), physical activity (nutritional intervention), gait speed (physical intervention), and energy (combination intervention). There were no major differences with respect to the small numbers of secondary outcomes. CONCLUSIONS: Physical, nutritional, and cognitive interventional approaches were effective in reversing frailty among community-living older persons. PMID- 26159635 TI - Digoxin: The Art and Science. AB - The use of digoxin in the therapy of systolic heart failure and certain supraventricular tachycardias is controversial. This review of the art and science of digoxin presents information needed by physicians considering digoxin therapy for these common cardiovascular disorders. PMID- 26159636 TI - Reinventing the US Institute of Medicine: A Second Coming. PMID- 26159637 TI - Family Business of Aortopathies. PMID- 26159638 TI - Bruised Black and Blue: Acquired Hypoprothrombinemia. PMID- 26159639 TI - The hierarchy of evidence and quantum theory. PMID- 26159640 TI - How to promote transparency and accountability in clinical and behavioral research. PMID- 26159641 TI - Proteomic analysis of murine testes lipid droplets. AB - Testicular Leydig cells contain abundant cytoplasmic lipid droplets (LDs) as a cholesteryl-ester store for releasing cholesterols as the precursor substrate for testosterone biosynthesis. Here, we identified the protein composition of testicular LDs purified from adult mice by using mass spectrometry and immunodetection. Among 337 proteins identified, 144 were previously detected in LD proteomes; 44 were confirmed by microscopy. Testicular LDs contained multiple Rab GTPases, chaperones, and proteins involved in glucuronidation, ubiquination and transport, many known to modulate LD formation and LD-related cellular functions. In particular, testicular LDs contained many members of both the perilipin family and classical lipase/esterase superfamily assembled predominately in adipocyte LDs. Thus, testicular LDs might be regulated similar to adipocyte LDs. Remarkably, testicular LDs contained a large number of classical enzymes for biosynthesis and metabolism of cholesterol and hormonal steroids, so steroidogenic reactions might occur on testicular LDs or the steroidogenic enzymes and products could be transferred through testicular LDs. These characteristics differ from the LDs in most other types of cells, so testicular LDs could be an active organelle functionally involved in steroidogenesis. PMID- 26159642 TI - Child maltreatment in United States military families: The military Family Advocacy Program has given increased attention to the prevention of family violence. PMID- 26159643 TI - Prehospital Stroke Identification: Factors Associated with Diagnostic Accuracy. AB - BACKGROUND: Stroke patients misdiagnosed by emergency medical services (EMS) providers have been shown to receive delayed in-hospital care. We aim at determining the diagnostic accuracy of Fire Department of New York (FDNY) EMS providers for stroke and identifying potential reasons for misdiagnosis. METHODS: Prehospital care reports of all patients transported by FDNY EMS to 3 hospitals from January 1, 2010, to December 31, 2011, were compared against the American Heart Association Get With The Guidelines (GWTG) database (reference standard) for the diagnosis of stroke. Age-adjusted logistic regression models were generated to explore prehospital patient characteristics which are associated with stroke misdiagnosis. RESULTS: Of 72,984 patient transports during the study period, 750 had a GWTG diagnosis of stroke, 468 (62%) of which were identified correctly in the field and 282 (38%) were missed. An additional 268 patients were misdiagnosed as stroke when in fact they had an alternative diagnosis. Overall sensitivity was 62.4% (95% confidence interval [CI], 58.9-65.8) and specificity was 99.6% (95% CI, 99.6-99.7). No patients who presented with unilateral weakness, facial weakness, or speech problems were missed, whereas patients with atypical complaints like general malaise, dizziness, and headache were more likely to be missed. Seizures led the EMS providers to both overcall a stroke and miss the diagnosis. CONCLUSIONS: FDNY EMS care providers missed more than a third of stroke cases. Seizures and other atypical presentations contribute significantly to stroke misdiagnosis in the field. Our findings highlight the need for better prehospital stroke identification methods. PMID- 26159644 TI - The Severity of White Matter Lesions Possibly Influences Stroke Recurrence in Patients with Histories of Lacunar Infarctions. AB - BACKGROUND: To investigate the recurrent stroke types associated with white matter lesions (WMLs), we prospectively observed recurrences in patients with histories of lacunar infarctions (LIs). METHODS: We prospectively analyzed the types of stroke recurrences in 305 patients (138 women, 70.2 +/- 11.7 years old) consecutively admitted to our hospital with LIs from April 2004 to December 2011. WMLs were graded using Fazekas' grades (Gr). Recurrence-free rate curves were generated by the Kaplan-Meier method using the log-rank test. RESULTS: The follow up period was 50.7 +/- 32.8 (.25-114) months. During this period, 62 strokes recurred. The incidences of strokes (all types), LIs, and deep intracerebral hemorrhages (ICHs) presenting as recurrences in 112 patients with Gr 2-3 were 6.2, 2.0, and 1.5 %/year, respectively, values that were significantly greater than those seen in 79 patients with Gr 0 (2.1 [P = .0001], .6 [P = .014], and .5 %/year [P = .016], respectively), and in 114 patients with Gr 1 (2.8 [P = .003], .9 [P = .009], and .6 %/year [P = .043], respectively). There was no significant difference among Gr 0, 1, and 2-3 in incidences of recurrences presenting as lobar ICHs, atherothrombotic infarctions, or cardioembolic infarctions. Multivariate analyses demonstrated that Gr 2-3 significantly and independently elevated the rate of deep ICHs or LIs presenting as recurrences after adjustment for risk factors. CONCLUSIONS: The presence of high-grade WMLs elevated the rate of stroke recurrences presenting as LIs and deep ICHs, but not other types. PMID- 26159645 TI - Endovascular Embolization of a Nondominant Vertebral Artery Compressed by an Osteophyte to Prevent Recurrence of Vertebrobasilar Infarctions. AB - BACKGROUND: Vertebral artery compression by cervical osteophyte is a rare cause of vertebrobasilar ischemic stroke. This mechanism of stroke has been reported as the Bow Hunter syndrome defined by vertebrobasilar insufficiency because of mechanical stenosis of the vertebral artery at the cervical level triggered by head movement. The most common treatment is surgical decompression. However, in most cases, a dominant vertebral artery is involved, and its dynamic extrinsic compression is demonstrated on angiography. CASE REPORT: We report a patient with recurrent posterior circulation infarctions because of the compression of a nondominant vertebral artery by a cervical osteophyte. The dynamic angiography did not show any worsening of the vertebral stenosis by head movements but an irregularity of the vertebral artery with regard to the osteophyte compression, suggesting a direct artery wall injury. We concluded to an embolic mechanism through thrombus formation from the artery wall injury at the stenosed site. Because neither surgical decompression nor stenting was deemed to be a relevant treatment option, endovascular coil embolization of the compressed vertebral artery was performed after a clamping test to check the efficiency of the collateral circulation. The procedure was a success. During the 12-month follow up, the patient did not have any recurrent stroke. CONCLUSIONS: In case of recurrent symptomatic extrinsic compression of a nondominant vertebral artery, endovascular embolization after a clamping test may be considered. PMID- 26159646 TI - Variants in the Atherogenic ALOX5AP, THBD, and KNG1 Genes Potentiate the Risk of Ischemic Stroke via a Genetic Main Effect and Epistatic Interactions in a Chinese Population. AB - BACKGROUND: Ischemic stroke (IS) is a multifactorial disease that displays a strong genetic predisposition. However, the genetic architecture of IS has yet to be fully elucidated. It was hypothesized that epistasis between genes in multiple atherothrombotic pathways may play a vital role in determining the susceptibility to IS. The aim of the present study was to investigate the contributions of the hypothesized genetic factors to IS and the interactions between these genetic factors in a Chinese population. METHODS: In this study, 351 cases with IS and 417 control subjects from a Chinese population were genotyped for single nucleotide polymorphisms (SNPs) in 12 genes hypothesized to be involved in atherosclerosis, coagulation, and related pathways. We examined SNP main effects and epistatic interactions between these polymorphic loci. RESULTS: rs710446 of the KNG1 gene was associated with IS susceptibility based on an additive genetic model (rs710446: P = .012; odds ratio [OR], 1.247; 95% confidence interval [CI], 1.050-1.481) after adjusting for covariates. Furthermore, an epistatic interaction between the ALOX5AP, THBD, and KNG1 gene was also identified in association with stroke susceptibility (P < .001 after 1000 permutations). Based on the chi-squared test, the OR of the high-risk combination of the three-locus model increased the risk of IS by 2.53-fold (95% CI, 1.60-4.01; P < .0001). CONCLUSIONS: Our findings support the association of the epistatic interactions of ALOX5AP, THBD, and KNG1 and present novel evidence for the main effect of KNG1 gene on IS susceptibility, suggesting a modulation of stroke risk by a genetic main effect and gene-gene interactions. PMID- 26159647 TI - Maternally derived trypsin may have multiple functions in the early development of turbot (Scopthalmus maximus). AB - Trypsin is an important serine protease that is considered to be involved in digestion of protein in teleost fish. Nevertheless, studies on trypsin/trypsinogen in fish embryos are very limited. In this study, the trypsinogen of turbot (Scophthalmus maximus) (tTG) was identified and the expression patterns and activity of trypsinogen/trypsin were investigated. The results showed that the tTG mRNA was evenly distributed in the oocytes and was also expressed along the yolk periphery in early embryos. At later embryo stages and 1 days after hatching (dph), the tTG mRNA concentrated at the alimentary tract and head. Quantitative expression analysis showed that the tTG transcripts decreased after fertilization until the gastrula stage, then increased with the embryo and larvae development. This result was also confirmed by the specific activity analysis of trypsin and in-situ-hybridization (ISH). All of the results indicated that tTG in early embryo stages was maternally derived and expressed by itself after gastrula stages. Additionally, location of tTG mRNA in embryos and larvae was investigated; we considered that trypsin may have multiple functions during the embryo development process. Based on our results regarding trypsinogen in embryos and early development, we concluded that the trypsin/trypsinogen in turbot embryos was inherited from a maternal source and we suggested that trypsin in early development has multiple functions in the process of development. PMID- 26159648 TI - In vitro oxygen exposure promotes maturation of the oxygen sensitive contraction in pre-term chicken ductus arteriosus. AB - The ductus arteriosus (DA) are O2-sensitive, embryonic blood vessels that serve as a right-to-left shunt in developing avian embryos. Prior to internal pipping, the chicken DA produces a weak O2-induced contraction. During hatching, the O2 sensitivity of the avian DA vessels increases significantly. To see if we could accelerate the maturation of chicken DA O2-sensitivity, we exposed the vessel in vitro to elevated O2 (25 kPa) for 3-h prior to internal pipping on day 19 of incubation. The DA initially responded to increasing O2 with a weak contraction (0.15+/-0.04 N/m) that significantly increased in strength (0.63+/-0.06 N/m) during 3-h 25 kPa O2 exposure. A tonic influence of nitric oxide, not present at low O2, appeared during the 3-h 25 kPa O2 exposure. The long-term O2-induced contraction was mediated by both L-type Ca(2+) channels and internal Ca(2+) stores. The Rho-kinase pathway inhibitors Y-27632 and fasudil produced significant relaxation, suggesting a role for Ca(2+) sensitization in the contractile response to the 3h of elevated O2. While the day 19 DA initially exhibited an immature contractile response to O2, maturation of the pathways regulating O2-induced contraction was accelerated by exposure to 25 kPa O2, producing contractions similar in magnitude to those found during the final stage of hatching. This suggests that maturation of O2-sensitivity may be accelerated in vivo by increasing arterial O2 levels. PMID- 26159650 TI - Clinical Management of Posterior Reversible Encephalopathy Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Series and Review of the Literature. AB - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). Among others, calcineurin inhibitors (CNI) for prophylaxis of graft versus-host disease (GvHD) may promote the development of PRES, but the pathomechanism is still controversial. Discontinuation of CNI facilitates remission of symptoms but might contribute to the unfavorable prognosis of PRES due to an elevated incidence of GvHD. METHODS: This is a case series of 7 patients with PRES from a retrospective analysis of 146 consecutive patients who received alloHSCT for hematologic malignancies. RESULTS: At the onset of PRES, all patients presented a systemic infection, while no influence was seen for underlying disease, conditioning regimen, donor type, or GvHD. Discontinuation of CNI and control of the blood pressure reversed neurological symptoms in 6 patients, while 1 patient died from septic multiorgan failure. After bridging with prednisolone and/or mycophenolic acid, replacement of CNI by the mammalian target of rapamycin (mTOR) inhibitor everolimus effectively prevented severe GvHD without recurrence of PRES. CONCLUSIONS: A systemic infection/inflammation may be an important cause of PRES. Prophylaxis of GvHD by the mTOR inhibitor everolimus in case of PRES after alloHSCT demonstrated promising results but needs to be validated in larger cohorts. PMID- 26159649 TI - A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening. AB - Sodium bicarbonate is a well-known antidote for tricyclic antidepressant (TCA) poisoning. It has been used for over half a century to treat toxin-induced sodium channel blockade as evidenced by QRS widening on the electrocardiogram (ECG). The purpose of this review is to describe the literature regarding electrophysiological mechanisms and clinical use of this antidote after poisoning by tricyclic antidepressants and other agents. This article will also address the literature supporting an increased serum sodium concentration, alkalemia, or the combination of both as the responsible mechanism(s) for sodium bicarbonate's antidotal properties. While sodium bicarbonate has been used as a treatment for cardiac sodium channel blockade for multiple other agents including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine, it has uncertain efficacy with bupropion, propranolol, and taxine-containing plants. PMID- 26159651 TI - Differential protein folding and chemical changes in lung tissues exposed to asbestos or particulates. AB - Environmental and occupational inhalants may induce a large number of pulmonary diseases, with asbestos exposure being the most risky. The mechanisms are clearly related to chemical composition and physical and surface properties of materials. A combination of X-ray fluorescence (MUXRF) and Fourier Transform InfraRed (MUFTIR) microscopy was used to chemically characterize and compare asbestos bodies versus environmental particulates (anthracosis) in lung tissues from asbestos exposed and control patients. MUXRF analyses revealed heterogeneously aggregated particles in the anthracotic structures, containing mainly Si, K, Al and Fe. Both asbestos and particulates alter lung iron homeostasis, with a more marked effect in asbestos exposure. MUFTIR analyses revealed abundant proteins on asbestos bodies but not on anthracotic particles. Most importantly, the analyses demonstrated that the asbestos coating proteins contain high levels of beta-sheet structures. The occurrence of conformational changes in the proteic component of the asbestos coating provides new insights into long-term asbestos effects. PMID- 26159652 TI - Update on percutaneous intervention for left main coronary artery stenosis. AB - Percutaneous coronary intervention (PCI) using drug-eluting stents (DES) is currently considered as a viable alternative to coronary artery bypass graft surgery (CABG) for selected patients with left main coronary artery disease. The updated results of the landmark randomized trials comparing CABG versus PCI demonstrated comparable 5-year outcomes and are in line with the current guidelines that designate PCI as a reasonable treatment in this disease subset. Given that the completed randomized trials did not include contemporary DESs, the upcoming results of the ongoing trials evaluating the performance of new generation DES compared with CABG (such as the EXCEL trial), may further help to clarify the current role and future recommendations of PCI for left main coronary artery disease. Apart from the recent stent technology, further improvements in outcomes after PCI may be possible when it is used with an integrated approach that combines functional concepts for decision-making, adjunctive imaging support and optimal pharmacotherapies. PMID- 26159654 TI - Erratum: MORC1 represses transposable elements in the mouse male germline. PMID- 26159653 TI - Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation. AB - Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology. PMID- 26159655 TI - Determining bronchial morphology for the purposes of segregating so-called heterotaxy. AB - Introduction Heterotaxy is a unique clinical entity in which lateralisation of the thoraco-abdominal organs is abnormal, typically with isomerism of the bronchial tree and atrial appendages. This study was carried out to determine whether routine clinical imaging such as chest radiographs, angiographic images, and CT/MRI can determine bronchial isomerism, and how sidedness of bronchial isomerism correlates with overall features anticipated in hearts with isomeric atrial appendages. Methods and results We identified 73 patients with heterotaxy, in whom imaging clearly demonstrated the bronchial tree, seen at our institution since 1998. We calculated bronchial angles and lengths using all the available imaging modalities to determine the presence and sidedness of bronchial isomerism. This was then compared with the anticipated presence of isomeric atrial appendages based on the overall clinical findings, as the appendages themselves had not specifically been imaged. The ratio of bronchial lengths revealed bronchial isomerism in all patients, with bronchial angles permitting distinction of right as opposed to left isomerism. We noted discordances between the identified bronchial isomerism and the presumed arrangement of the atrial appendages in nearly 20% of the patients in our cohort. CONCLUSION: Routine clinical imaging with chest radiographs, angiographic imaging, and CT/MRI can determine the presence of bronchial isomerism in patients with so-called heterotaxy. Right as opposed to left isomerism can be distinguished based on bronchial angles. The finding of bronchial isomerism correlates well, but not totally, with the presumed isomerism of the atrial appendages as predicted from the identified intra-cardiac morphology. PMID- 26159656 TI - Grover's disease and cutaneous melanoma: a fortuitous association or a paraneoplastic case? PMID- 26159657 TI - Alexithymia, dissociation, and trauma in patients with chronic skin conditions. AB - BACKGROUND: There is considerable literature concerning psychological distress and dermatological diseases. Recent studies highlight the role of emotion dysregulation in several skin diseases. Our study sought to explore emotion regulation in patients with chronic skin conditions and the frequency of traumatic experiences they had encountered. METHODS: Forty-nine sequential dermatological patients were compared with 49 healthy adults. Both groups were studied by means of validated scales for alexithymia (Toronto Alexithymia Scale [TAS-20]) and dissociation (Dissociation Experiences Scale [DES-II] and they completed a checklist for traumatic events (Traumatic Experiences Checklist [TEC]). RESULTS: Our results indicated that subjects suffering from chronic dermatological diseases presented more severe alexithymic and dissociative traits. Furthermore, they had suffered a greater number of stressful experiences than had individuals in the control group. CONCLUSIONS: Our findings appear to be consistent with literature linking skin diseases and emotion regulation, highlighting a psychosomatic specificity in these conditions. PMID- 26159658 TI - Dynamic Solvent Control of a Reaction in Ionic Deep Eutectic Solvents: Time Resolved Fluorescence Measurements of Reactive and Nonreactive Dynamics in (Choline Chloride + Urea) Melts. AB - Dynamic fluorescence anisotropy and Stokes shift measurements of [f choline chloride + (1 - f) urea)] deep eutectic solvents at f = 0.33 and 0.40 have been carried out using a dipolar solute, coumarin 153 (C153), in the temperature range 298 <= T <= 333 K. Subsequently, measured time-dependent solvent response is utilized to investigate the dynamic solvent control on the measured rates of photoexcited intramolecular charge transfer (ICT) reactions of two molecules, 4 (1-azetidinyl)benzonitrile (P4C) and 4-(1-pyrrolidinyl)benzonitrile (P5C), occurring in these media. Measured average reaction time scales (?tau(rxn)?) exhibit the following dependence on average solvation times scales (?tau(s)?): ?tau(rxn)? ? ?tau(s)?(alpha) with alpha = 0.5 and 0.35 for P4C and P5C, respectively. Such a strong dynamic solvent control of ?tau(rxn)?, particularly for P4C, is different from earlier observations with these ICT molecules in conventional molecular solvents. Excitation wavelength-dependent fluorescence emissions of C153 and trans-2-[4-(dimethylamino)styryl]-benzothiazole (DMASBT), which differ widely in average fluorescence lifetimes (?tau(life)?), suggest the presence of substantial spatial heterogeneity in these systems. Dynamic heterogeneity is reflected via the following fractional viscosity (eta) dependences of ?tau(s)? and ?tau(r)? (?tau(r)? being solute's average rotation time): ?taux? ? (eta/T)(p) with 0.7 <= p <= 0.9. Different correlations between ?tau(s)? and ?tau(r)? emerge at different temperature regimes, indicating variable frictional coupling at low and high temperatures. Estimated dynamic Stokes shifts in these media vary between ~1200 and ~1600 cm(-1), more than 50% of which possess a time scale much faster than the temporal resolution (~75 ps) employed in these measurements. Estimated activation energy for eta is closer to that for ?tau(r)? than that for ?tau(s)?, suggesting ?tau(s)? being more decoupled from eta than ?tau(r)?. PMID- 26159659 TI - Preparation and characterization of alginate-gelatin microencapsulated Bacillus subtilis SL-13 by emulsification/internal gelation. AB - Gelatin was blended with sodium alginate (NaALG) to obtain a novel microbial fungicide, and dispersed micron Bacillus subtilis SL-13 microspheres prepared by emulsification/internal gelation method. Microscopic examination revealed that microcapsules were nearly spherical in shape. Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction confirmed that the electrostatic interaction was occurred when gelatin added into NaALG. The maximum encapsulation efficiency was 93.44% at a gelatin concentration of 1.5%. Particle size, swelling, and biodegradation of beads increased with gelatin content increase. Furthermore, the viability of encapsulated SL-13 could be preserved at more than 10(8) CFU/mL after 120 d storage at 25 degrees C. The number of viable cells released from microcapsules presented an initial rapid increase followed by a gradual increase, and reached the maximum as 10(10) CFU/mL on day 35. Thus, it is feasible to prepare uniform, rounded shape, and well dispersed micron microcapsules of SL-13 via emulsification/internal gelation using NaALG and gelatin composites. This encapsulation strategy could be considered as a potential alternative to future applications in the agricultural industry. PMID- 26159660 TI - Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry. AB - PURPOSE: Geant4-DNA is used to calculate S-values for different subcellular distributions of low-energy electron sources in various cell geometries. METHOD: Calculations of cellular S-values for monoenergetic electron sources with energy from 1 to 100 keV and the Auger-electron emitting radionuclides Tc-99m, In-111, and I-125 have been made using the Geant4 Monte Carlo toolkit. The Geant4-DNA low energy extension is employed for simulating collision-by-collision the complete slowing-down of electron tracks (down to 8 eV) in liquid water, used as a surrogate of human cells. The effect of cell geometry on S-values is examined by simulating electron tracks within different cell geometries, namely, a spherical, two ellipsoidal, and an irregular shape, all having equal cellular and nuclear volumes. Algorithms for randomly sampling the volume of the nucleus, cytoplasm, surface, and whole cell for each cell phantom are presented. RESULTS: Differences between Geant4-DNA and MIRD database up to 50% were found, although, for the present radionuclides, they mostly remain below 10%. For most source-target combinations the S-values for the spherical cell geometry were found to be within 20% of those for the ellipsoidal cell geometries, with a maximum deviation of 32%. Differences between the spherical and irregular geometries are generally larger reaching 100-300%. Most sensitive to the cell geometry is the absorbed dose to the nucleus when the source is localized on the cell surface. Interestingly, two published AAPM spectra for I-125 yield noticeable differences (up to 19%) in cellular S-values. CONCLUSION: Monte Carlo simulations of cellular S-values with Geant4-DNA reveal that, for the examined radionuclides, the widely used approximation of spherical cells is reasonably accurate (within 20-30%) even for ellipsoidal geometries. For irregular cell geometries the spherical approximation should be used with caution because, as in the present example, it may lead to erroneous results for the nuclear dose for the commonly encountered situation where the source is localized to the cell surface. PMID- 26159661 TI - Automated electrophilic radiosynthesis of [18F]FBPA using a modified nucleophilic GE TRACERlab FXFDG. AB - We modified a commercially available synthesis module for nucleophilic [(18)F]fluorinations (TRACERlab(TM) FXFDG, GE Healthcare) to enable the reliable synthesis of 2-[(18)F]fluoro-4-borono-L-phenylalanine ([(18)F]FBPA) via direct electrophilic substitution of 4-borono-L-phenylalanine with [(18)F]F2 gas. [(18)F]FBPA was obtained with a RCY of 8.5+/-2.0% and a radiochemical purity of 98+/-1% in a total synthesis time of 72+/-7 min (n=22). The modified synthesis module might also be useful for the synthesis of other [(18)F]radiopharmaceuticals via electrophilic substitution reactions while still being suitable for nucleophilic substitution reactions. PMID- 26159662 TI - Improved synthesis of [18F]FS-PTAD as a new tyrosine-specific prosthetic group for radiofluorination of biomolecules. AB - A novel prosthetic group, 4-(p-([(18)F]fluorosulfonyl)phenyl)-1,2,4-triazoline 3,5-dione ([(18)F]FS-PTAD) for site-specific radiofluorination of tyrosine residue in small molecules is described. Coupling of [(18)F]FS-PTAD with L tyrosine, N-acetyl-L-tyrosine methyl amide and phenol as model compounds were achieved in buffered aqueous solution at room temperature, resulting in the corresponding fluorinated tyrosine and phenol derivatives. The total synthesis time including radiosynthesis, HPLC purification and formulation was less than 60 min (n=15) with >=98% radio chemical purity. An initial in vitro evaluation of [(18)F]FS-PTAD-tyrosine in glioma cell lines revealed moderate uptake. PMID- 26159663 TI - Application of support vector machine to rapid classification of uranium waste drums using low-resolution gamma-ray spectra. AB - We investigated the feasibility of using support vector machine (SVM), a computer learning method, to classify uranium waste drums as natural uranium or reprocessed uranium based on their origins. The method was trained using 12 training datasets were used and tested on 955 datasets of gamma-ray spectra obtained with NaI(Tl) scintillation detectors. The results showed that only 4 out of 955 test datasets were different from the original labels-one of them was mislabeled and the other three were misclassified by SVM. These findings suggest that SVM is an effective method to classify a large quantity of data within a short period of time. Consequently, SVM is a feasible method for supporting the scaling factor method and as a supplemental tool to check original labels. PMID- 26159664 TI - Sphingomonas chloroacetimidivorans sp. nov., a chloroacetamide herbicide degrading bacterium isolated from activated sludge. AB - Strain Y1(T), a Gram-negative, non-spore-forming, rod-shaped bacterium, was isolated from activated sludge. This strain is able to degrade several commonly used chloroacetamide herbicides, such as butachlor, acetochlor and alachlor. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Y1(T) is a member of the genus Sphingomonas and shows high sequence similarities with S. starnbergensis 382(T) (95.7 %), S. sanxanigenens NX02(T) (95.7 %) and S. haloaromaticamans A175(T) (95.3 %), and shows low (<95 %) sequence similarities to all other Sphingomonas species. Chemotaxonomic analysis revealed that strain Y1(T) possesses Q-10 as the predominant ubiquinone, C14:0 2-OH as the major 2 hydroxy fatty acid and sym-homospermidine as the major polyamine. The main cellular fatty acids of strain Y1(T) were found to be C18:1 omega7c (38.2 %), C16:1 omega6c/C16:1 omega7c (28.5 %), C16: 0 (10.7 %) and C14:0 2-OH (14.3 %). The main polar lipids were determined to be diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipids (SGL1-SGL3), phosphatidyl dimethylethanolamine and aminophospholipid. The DNA G+C content was found to be 66 +/- 0.4 mol%. Based on phylogenetic analysis, phenotypic characteristics and chemotaxonomic data, strain Y1(T) is considered to represent a novel species of the genus Sphingomonas, for which the name Sphingomonas chloroacetimidivorans sp. nov. is proposed. The type strain is Y1(T) (=CCTCC AB 2011178(T) = KACC 16607(T)). PMID- 26159665 TI - Equivalent spin-orbit interaction in the two-polariton Jaynes-Cummings-Hubbard model. AB - A cavity quantum electrodynamics (cavity-QED) system combines two or more distinct quantum components, exhibiting features not seen in the individual systems. In this work, we study the one-dimensional Jaynes-Cummings-Hubbard model in the two-excitation (two-polariton) subspace. We find that the centre momentum of two-excitation induces a magnetic flux piercing the equivalent Hamiltonian Hk in the invariant subspace with momentum k, which can be described as a 4-leg ladder in the auxiliary space. Furthermore, it is shown that the system in pi centre-momentum subspace is equivalent to a lattice system for spin-1 particle with spin-orbit coupling. On the basis of this concise description, a series of bound-pair eigenstates which display long-range polaritonic entanglement is presented as a simple application. PMID- 26159666 TI - [Patient with a Fontan circulation undergoing caesarean section: Anesthesiological management]. AB - Adults suffering from congenital heart diseases (CHD) represent a challenge to anesthesiologists because of the diverse pathologies, complex pathophysiology and special treatment strategies. Due to improved therapeutic options for CHD, patient quality of life and life expectancy is increasing, leaving them as a growing population including pregnant patients with CHD. This article presents the main principles of the pathophysiology and anesthesiological management of pregnant patients living with a Fontan circulation based on a case report, which was complicated by an aortic coarctation and atonic uterine hemorrhage. PMID- 26159668 TI - [Comments on: High-flow oxygen administration through a nasal cannula in acute hypoxemic respiratory failure]. PMID- 26159667 TI - [CVP - farewell? Please don't! : Comments on the S3 guidelines on "intravascular volume therapy in adults"]. PMID- 26159669 TI - Topographic deficits in alpha-range resting EEG activity and steady state visual evoked responses in schizophrenia. AB - Deficits in both resting alpha-range (8-12Hz) electroencephalogram (EEG) activity and steady state evoked potential (SSVEP) responses have been reported in schizophrenia. However, the topographic specificity of these effects, the relationship between resting EEG and SSVEP, as well as the impact of antipsychotic medication on these effects, have not been clearly delineated. The present study sought to address these questions with 256 channel high-density EEG recordings in a group of 13 schizophrenia patients, 13 healthy controls, and 10 non-schizophrenia patients with psychiatric diagnoses currently taking antipsychotic medication. At rest, the schizophrenia group demonstrated decreased alpha EEG power in frontal and occipital areas relative to healthy controls. With SSVEP stimulation centered in the alpha band (10Hz), but not with stimulation above (15Hz) or below (7Hz) this range, the occipital deficit in alpha power was partially reverted. However, the frontal deficit persisted and contributed to a significantly reduced topographic relationship between occipital and frontal alpha activity for resting EEG and 10Hz SSVEP alpha power in schizophrenia patients. No significant differences were observed between healthy and medicated controls or between medicated controls and schizophrenia. These findings suggest a potential intrinsic deficit in frontal eyes-closed EEG alpha oscillations in schizophrenia, whereby potent visual stimulation centered in that frequency range results in an increase in the occipital alpha power of these patients, which however does not extend to frontal regions. Future research to evaluate the cortical and subcortical mechanisms of these effects is warranted. PMID- 26159670 TI - A GATA2/3 gene potentially involved in larval shell formation of the Pacific oyster Crassostrea gigas. AB - Shells are one of the most notable features of the majority of mollusks. In addition, the shell is also considered a key characteristic during molluscan evolution and development. However, although the morphological changes during larval shell formation have been well described, the underlying molecular mechanisms remain poorly understood. In this study, we focused on the potential involvement of a GATA gene in shell formation because GATA genes are often downstream genes of BMP (bone morphogenetic protein) signaling pathways, which have been suggested to participate in molluscan shell formation. In the Pacific oyster Crassostrea gigas, we observed that the expression of a GATA2/3 homolog (cgi-gata2/3) was clearly restricted to the edge of the shell field in early larval stages (trochophore and D-veliger). This expression pattern supports the notion that cgi-gata2/3 gene plays conserved roles in bilaterian ectodermal development. It is possible that cgi-gata2/3 is one shell-formation gene under the regulation of BMP signaling pathways. In addition, cgi-gata2/3 was also detected in the ventral side of embryos. The expression of cgi-gata2/3 away from the shell field may be involved in hematopoiesis. Our results provide fundamental support for studies into the molecular mechanisms of larval shell formation and the functions of molluscan GATA genes. PMID- 26159671 TI - Perfluoroalkyl substances measured in breast milk and child neuropsychological development in a Norwegian birth cohort study. AB - Perfluoroalkyl substances (PFASs) are chemicals with potential neurotoxic effects although the current evidence is still limited. This study investigated the association between perinatal exposure to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and neuropsychological development assessed at 6, 12 and 24 months. We measured PFOS and PFOA in breast milk samples collected one month after delivery by mothers of children participating in the HUMIS study (Norway). Cognitive and psychomotor development was measured at 6 and at 24 months using the Ages and Stages Questionnaire (ASQ-II). Behavioral development was assessed using the infant-toddler symptom checklist (ITSC) at 12 and at 24 months. Weighted logistic regression and weighted negative binomial regression models were applied to analyze the associations between PFASs and ASQ-II and ITSC, respectively. The median concentration of PFOS was 110 ng/L, while the median for PFOA was 40 ng/L. We did not detect an increased risk of having an abnormal score in ASQ-II at 6 months or 24 months. Moreover, no consistent increase in behavioral problems assessed at 12 and 24 months by ITSC questionnaire was detected. We observed no association between perinatal PFOS and PFOA exposure and early neuropsychological development. Further longitudinal studies are needed to confirm the effects of these compounds on neuropsychological development in older children. PMID- 26159672 TI - Role of innate immune system in systemic sclerosis. AB - Recognition of microbial or viral compounds is crucial to elicit an immune response and pattern recognition receptors (PRRs) form the first line of defence. An important family of PRRs are the Toll-like receptors (TLRs) with numerous evidences indicating their crucial role in identifying microbial or viral compounds. However, the danger theory, where the innate immune system responds to danger signals such as proteins released during damage or necrosis rather than only non-self is gaining ground. Indeed, TLRs are able to recognise endogenous molecules and have been implicated as key players in numerous autoimmune diseases including systemic sclerosis (SSc). TLR2 is known to be upregulated in SSc and has been shown to respond to the endogenous ligand amyloid A resulting in increased IL-6 secretion. TLR4 is now known to respond to a variety of endogenous ligands including fibronectin, containing alternatively spliced exons encoding type III repeat extra domain (EDA). EDA is only expressed upon tissue damage, and elevated levels can be found in SSc patients, idiopathic pulmonary fibrosis and cardiac allograft fibrosis, while deletion of EDA or TLR4 in mice reduces their fibrotic response. Further, stimulation of TLR8 with single-stranded RNA leads to increased expression of TIMP-1. This has been shown to require both IRAK4 and NF kappaB with evidence suggesting autoantibodies bind to RNA to stimulate TIMP-1 production in monocytes. Therefore, TLR-mediated signalling provides numerous potential therapeutic targets for development of therapies for the treatment of multi-systemic autoimmune diseases. PMID- 26159673 TI - Measurement of homoarginine in human and mouse plasma by LC-MS/MS and ELISA: a comparison and a biological application. AB - Homoarginine (hArg) is a non-essential amino acid that was identified as a risk marker for cardiovascular disease. Several analytical methods have been described for the quantification of hArg in biological samples. The aim of this study was to compare a liquid chromatography-tandem mass spectrometric (LC-MS/MS) approach with a commercially available enzyme-linked immunosorbent assay (ELISA). Determination of hArg concentrations in ELISA calibration standards measured by both methods revealed a correlation coefficient r (2) of 0.99, for LC-MS/MS calibrators r (2) was 0.997. However, linear regression analysis between the two assays for hArg concentrations in human plasma samples revealed a correlation coefficient r (2) of 0.78. Plasma concentrations obtained from LC-MS/MS are on average 29 % higher than those by ELISA. We investigated the hArg-isobaric N (epsilon)-trimethyllysine as potential source for the higher observed values, but evaluation of mass spectra indicated that N (epsilon)-trimethyllysine did not interfere with hArg quantification in our LC-MS/MS method. Both quantification methods were applied to measure hArg in (1) a case-control study of acute coronary syndrome and (2) L-arginine:glycine amidinotransferase-deficient mice. Our LC-MS/MS and the commercially available ELISA assay are suitable for hArg measurement in human and mouse plasma, but different reference values for each method need to be considered. PMID- 26159674 TI - A self-regulating antimicrobial model based on the ion-exchange stimuli. AB - In this study, a novel intelligent antimicrobial model was constructed based on the antibiotic properties of nano-silver and the ion-exchange response of dehydrated alginate (Alg) gel. Through the process of reducing reaction, hydrogel formation and dehydration, the model composed of Alg and nano-silver was fabricated. The distinguished feature of this model lies in its antimicrobial properties and biocompatibility. In this model, the releasing level of nano silver is determined by the outside-in swelling of Alg composites, which is further self-regulated by the volume of wound exudates. The results showed that the released nano-silver was intelligently maintained within a constant concentration range, so that it could be further designed to exhibit antimicrobial activity without cytotoxicity. Furthermore, the murine wound infection model conducted with these composites resulted in a significant decrease of bacteria number. The self-regulating swelling feature based on the ion-exchange response of Alg along with the controlled release of nano-silver made this composite a promising intelligent model for antimicrobial wound dressing applications. PMID- 26159675 TI - Partial replacements of Stylosanthes scabra forage for lucerne in total mixed ration diet of Saanen goats. AB - The inclusion of Stylosanthes scabra cv. Seca forage in the total mixed ration (TMR) as partial replacement of lucerne (alfalfa) was evaluated for its effects on voluntary feed intake, nutrient digestibility and nitrogen balance in Saanen goats. Three experimental diets were formulated having 0 % Seca (T1), 15 % Seca (T2) and 30 % Seca (T3) as partial replacement of lucerne forage in the TMR diet for goats. Eighteen Saanen goats of about 7 months old were divided into three groups of six animals per group. Each group was randomly assigned to one of the three dietary treatments in a complete randomised design, and the study lasted for a period of 21 days. There was an increase in fibre and mineral content of the diets as Seca inclusion increased, but this resulted in the decrease of crude protein contents and in vitro organic matter digestibility. Animals that were fed 15 % Seca recorded higher voluntary dry matter and nutrient (organic matter and fibres) intake, but the difference was not statistically significant (P > 0.05) as compared to the other treatments. Nutrient digestibility as well as nitrogen balance was not significantly different across the three diets. The lack of significant differences in feed intake, nutrient digestibility and nitrogen utilisation following the inclusion of Seca in the TMR suggests that S. scabra forage can partially replace lucerne in the TMR diet of goats. PMID- 26159678 TI - Escin Increases the Survival Rate of LPS-Induced Septic Mice Through Inhibition of HMGB1 Release from Macrophages. AB - BACKGROUND: Previous studies have described the effects of Escin on improving the survival rate of endotoxemic animals. The purpose of this study was to explore the molecular mechanisms of this potentially beneficial treatment. METHODS: First, the survival rate of endotoxemic mice was monitored for up to 2 weeks after Escin pretreatment, Escin post-treatment, or Escin post-treatment + rHMGB1. The effects of Escin on the release of pro-inflammatory cytokines such as TNF alpha, IL-1beta, IL-6 and HMGB1 in the serum of endotoxemic mice and LPS-induced macrophages were evaluated by ELISA. Furthermore, the mRNA and protein levels of HMGB1 in LPS-induced macrophages were measured by qRT-PCR and Western blot, respectively. Additionally, the release of pro-inflammatory cytokines such as TNF alpha, IL-1beta, IL-6 was evaluated by ELISA in rHMGB1-induced macrophages. Finally, the protein levels and the activity of NF-kappaB in macrophages were checked by Western blot and ELISA, respectively. RESULTS: Both pretreatment and post-treatment with Escin could improve the survival rate of endotoxemic mice, while exogenous rHMGB1 reversed this effect. In addition, Escin decreased the level of the pro-inflammatory cytokinesTNF-alpha,IL-1beta, IL-6 and HMGB1 in endotoxemic mice and in LPS-induced macrophages. Escin could also inhibit the mRNA levels and activity of HMGB1. The release of the pro-inflammatory cytokinesTNF-alpha,IL-1beta, IL-6 could be suppressed in rHMGB1-induced macrophages by Escin. Finally, Escin could suppress the activation of NF- kappaB in LPS-induced macrophages. CONCLUSION: Escin could improve the survival of mice with LPS-induced endotoxemia. This effect maybe meditated by reducing the release of HMGB1, resulting in the suppression of the release of pro-inflammatory cytokines. PMID- 26159679 TI - A theoretical investigation of substituent effects on the stability and reactivity of N-heterocyclic olefin carboxylates. AB - A theoretical study of substituent effects on the stability and reactivity of novel synthesized N-heterocyclic olefin (NHO) carboxylates has been performed using a combination of density functional theory (DFT) calculations, molecular electrostatic potential (MESP) minimum and nucleophilicity index analyses. These calculations demonstrate that the nucleophilicity of free NHO is stronger than that of the NHO-CO2 adduct and, hence, the thermally unstable NHO-CO2 adduct should be a more efficient organocatalyst for nucleophile-mediated reactions. The stability of the NHO-CO2 adduct, as well as the reactivity of free NHO, is strongly dependent on the electronic and steric effects of the C- and N substituents on the imidazole ring. This dependency is reflected by the measured MESP minimum for the carboxylate moiety, the NHO-CO2 adduct (Vmin1), and the terminal carbon atom of free NHO (Vmin2). C-Substituents exert only electronic effects while N-substituents exert both electronic and steric effects. In general, the electron-withdrawing groups on the C- and N-positions favor decarboxylation while weakening the reactivity of NHO. These positions favor decarboxylation due to the simultaneous decrease of the electronic density on the carboxyl moiety of the NHO-CO2 and the terminal carbon atom of olefins. Additionally, the balance between the stability of the NHO-CO2 and the reactivity of free NHO can be tuned by the combined effects of the C- and N-substituents. The introduction of weak electron-withdrawing groups at the C-position and aromatic substituents or similar ring-strained entities at the N-position favors decarboxylation of the NHO-CO2 adduct and ensures the free NHO as a strong nucleophile. PMID- 26159677 TI - Hypertension and Stroke: Epidemiological Aspects and Clinical Evaluation. AB - The strong relationship between stroke and hypertension has been the object of several studies and trials. These studies addressed the epidemiology of stroke and hypertension, in order to estimate their worldwide distribution and time evolution, and investigated the effects of the management of hypertension on stroke outcomes. Evidences coming from these studies are essential to plan proper health services, optimise economic resources, and estimate the effectiveness of therapeutic strategies in primary and secondary prevention. Additional suggestions are needed to tailor the pharmacologic management of hypertension on the individual needs of patients and to select the most appropriate treatment to avoid stroke recurrences on the basis of the first-ever stroke subtype. Moreover, an increasing attention has been given, over the last years, to the relationship between the presence of hypertension and the development of an end-organ brain damage leading to early cognitive dysfunctions. A better understanding of this relationship is the prerequisite to promote successful aging and well-being. PMID- 26159676 TI - Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury. AB - Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and regeneration. We investigated the diagnostic and prognostic values of serum BDNF in traumatic brain injury (TBI). We examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency departments (EDs) of the Johns Hopkins Hospital (JHH; n = 76) and San Francisco General Hospital (SFGH, n = 80), and a control group of JHH ED patients without TBI (n = 150). Findings were subsequently validated in the prospective, multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study (n = 159). We investigated the association between BDNF, glial fibrillary acidic protein (GFAP), and ubiquitin C terminal hydrolase-L1 (UCH-L1) and recovery from TBI at 6 months in the TRACK-TBI Pilot cohort. Incomplete recovery was defined as having either post-concussive syndrome or a Glasgow Outcome Scale Extended score <8 at 6 months. Median day-of injury BDNF concentrations (ng/mL) were lower among TBI cases (JHH TBI, 17.5 and SFGH TBI, 13.8) than in JHH controls (60.3; p = 0.0001). Among TRACK-TBI Pilot subjects, median BDNF concentrations (ng/mL) were higher in mild (8.3) than in moderate (4.3) or severe TBI (4.0; p = 0.004. In the TRACK-TBI cohort, the 75 (71.4%) subjects with very low BDNF values (i.e., =5 MUg/ml), significantly decreased forward scatter (>=5 MUg/ml), significantly increased ROS abundance (5 MUg/ml), significantly increased [Ca2+]i (7.5 MUg/ml) and significantly increased ceramide abundance (10 MUg/ml). The up-regulation of annexin- V-binding following mefloquine treatment was significantly blunted but not abolished by removal of extracellular Ca2+. Even in the absence of extracellular Ca2+, mefloquine significantly increased annexin-V-binding. CONCLUSIONS: Mefloquine treatment leads to erythrocyte shrinkage and erythrocyte membrane scrambling, effects at least partially due to induction of oxidative stress, increase of [Ca2+]i and up-regulation of ceramide abundance. PMID- 26159704 TI - A New Versatile Immobilization Tag Based on the Ultra High Affinity and Reversibility of the Calmodulin-Calmodulin Binding Peptide Interaction. AB - Reversible, high-affinity immobilization tags are critical tools for myriad biological applications. However, inherent issues are associated with a number of the current methods of immobilization. Particularly, a critical element in phage display sorting is functional immobilization of target proteins. To circumvent these problems, we have used a mutant (N5A) of calmodulin binding peptide (CBP) as an immobilization tag in phage display sorting. The immobilization relies on the ultra high affinity of calmodulin to N5A mutant CBP (RWKKNFIAVSAANRFKKIS) in presence of calcium (KD~2 pM), which can be reversed by EDTA allowing controlled "capture and release" of the specific binders. To evaluate the capabilities of this system, we chose eight targets, some of which were difficult to overexpress and purify with other tags and some had failed in sorting experiments. In all cases, specific binders were generated using a Fab phage display library with CBP fused constructs. KD values of the Fabs were in subnanomolar to low nanomolar (nM) ranges and were successfully used to selectively recognize antigens in cell based experiments. Some of these targets were problematic even without any tag; thus, the fact that all led to successful selection endpoints means that borderline cases can be worked on with a high probability of a positive outcome. Taken together with examples of successful case specific, high-level applications like generation of conformation-, epitope- and domain-specific Fabs, we feel that the CBP tag embodies all the attributes of covalent immobilization tags but does not suffer from some of their well-documented drawbacks. PMID- 26159703 TI - Prophylactic melatonin significantly reduces Alzheimer's neuropathology and associated cognitive deficits independent of antioxidant pathways in AbetaPP(swe)/PS1 mice. AB - BACKGROUND: Alzheimer's disease (AD) underlies dementia for millions of people worldwide, and its occurrence is set to double in the next 20 years. Currently, approved drugs for treating AD only marginally ameliorate cognitive deficits, and provide limited symptomatic relief, while newer substances under therapeutic development are potentially years away from benefiting patients. Melatonin (MEL) for insomnia has been proven safe with >15 years of over-the-counter access in the US. MEL exerts multiple complementary mechanisms of action against AD in animal models; thus it may be an excellent disease-modifying therapeutic. While presumed to provide neuroprotection via activation of known G-protein-coupled melatonin receptors (MTNRs), some data indicate MEL acts intracellularly to protect mitochondria and neurons by scavenging reactive oxygen species and reducing free radical formation. We examined whether genetic deletion of MTNRs abolishes MEL's neuroprotective actions in the AbetaPP(swe)/PSEN1dE9 mouse model of AD (2xAD). Beginning at 4 months of age, both AD and control mice either with or without both MTNRs were administered either MEL or vehicle in drinking water for 12 months. RESULTS: Behavioral and cognitive assessments of 15-month-old AD mice revealed receptor-dependent effects of MEL on spatial learning and memory (Barnes maze, Morris Water Maze), but receptor-independent neuroprotective actions of MEL on non-spatial cognitive performance (Novel Object Recognition Test). Similarly, amyloid plaque loads in hippocampus and frontal cortex, as well as plasma Abeta1-42 levels, were significantly reduced by MEL in a receptor independent manner, in contrast to MEL's efficacy in reducing cortical antioxidant gene expression (Catalase, SOD1, Glutathione Peroxidase-1, Nrf2) only when receptors were present. Increased cytochrome c oxidase activity was seen in 16 mo AD mice as compared to non-AD control mice. This increase was completely prevented by MEL treatment of 2xAD/MTNR+ mice, but only partially prevented in 2xAD/MTNR- mice, consistent with mixed receptor-dependent and independent effects of MEL on this measure of mitochondrial function. CONCLUSIONS: These findings demonstrate that prophylactic MEL significantly reduces AD neuropathology and associated cognitive deficits in a manner that is independent of antioxidant pathways. Future identification of direct molecular targets for MEL action in the brain should open new vistas for development of better AD therapeutics. PMID- 26159706 TI - Proteomic analysis of purified turkey adenovirus 3 virions. AB - Turkey adenovirus 3 (TAdV-3) causes high mortality and significant economic losses to the turkey industry. However, little is known about the molecular determinants required for viral replication and pathogenesis. Moreover, TAdV-3 does not grow well in cell culture, thus detailed structural studies of the infectious particle is particularly challenging. To develop a better understanding of virus-host interactions, we performed a comprehensive proteomic analysis of proteinase K treated purified TAdV-3 virions isolated from spleens of infected turkeys, by utilizing one-dimensional liquid chromatography mass spectrometry. Our analysis resulted in the identification of 13 viral proteins associated with TAdV-3 virions including a novel uncharacterized TaV3gp04 protein. Further, we detected 18 host proteins in purified virions, many of which are involved in cell-to cell spread, cytoskeleton dynamics and virus replication. Notably, seven of these host proteins have not yet been reported to be present in any other purified virus. In addition, five of these proteins are known antiviral host restriction factors. The availability of reagents allowed us to identify two cellular proteins (collagen alpha-1 (VI) chain and haemoglobin) in the purified TAdV-3 preparations. These results represent the first comprehensive proteomic profile of TAdV-3 and may provide information for illustrating TAdV-3 replication and pathogenesis. PMID- 26159707 TI - From the periphery to the brain: Lipocalin-2, a friend or foe? AB - Lipocalin-2 (LCN2) is an acute-phase protein that, by binding to iron-loaded siderophores, acts as a potent bacteriostatic agent in the iron-depletion strategy of the immune system to control pathogens. The recent identification of a mammalian siderophore also suggests a physiological role for LCN2 in iron homeostasis, specifically in iron delivery to cells via a transferrin-independent mechanism. LCN2 participates, as well, in a variety of cellular processes, including cell proliferation, cell differentiation and apoptosis, and has been mostly found up-regulated in various tissues and under inflammatory states, being its expression regulated by several inducers. In the central nervous system less is known about the processes involving LCN2, namely by which cells it is produced/secreted, and its impact on cell proliferation and death, or in neuronal plasticity and behaviour. Importantly, LCN2 recently emerged as a potential clinical biomarker in multiple sclerosis and in ageing-related cognitive decline. Still, there are conflicting views on the role of LCN2 in pathophysiological processes, with some studies pointing to its neurodeleterious effects, while others indicate neuroprotection. Herein, these various perspectives are reviewed and a comprehensive and cohesive view of the general function of LCN2, particularly in the brain, is provided. PMID- 26159708 TI - Visual attention: Linking prefrontal sources to neuronal and behavioral correlates. AB - Attention is a means of flexibly selecting and enhancing a subset of sensory input based on the current behavioral goals. Numerous signatures of attention have been identified throughout the brain, and now experimenters are seeking to determine which of these signatures are causally related to the behavioral benefits of attention, and the source of these modulations within the brain. Here, we review the neural signatures of attention throughout the brain, their theoretical benefits for visual processing, and their experimental correlations with behavioral performance. We discuss the importance of measuring cue benefits as a way to distinguish between impairments on an attention task, which may instead be visual or motor impairments, and true attentional deficits. We examine evidence for various areas proposed as sources of attentional modulation within the brain, with a focus on the prefrontal cortex. Lastly, we look at studies that aim to link sources of attention to its neuronal signatures elsewhere in the brain. PMID- 26159709 TI - Kinetics of the unimolecular reaction of CH2OO and the bimolecular reactions with the water monomer, acetaldehyde and acetone under atmospheric conditions. AB - Stabilized Criegee Intermediates (sCIs) have been identified as oxidants of atmospheric trace gases such as SO2, NO2, carboxylic acids or carbonyls. The atmospheric sCI concentrations, and accordingly their importance for trace gas oxidation, are controlled by the rate of the most important loss processes, very likely the unimolecular reactions and the reaction with water vapour (monomer and dimer) ubiquitously present at high concentrations in the troposphere. In this study, the rate coefficients of the unimolecular reaction of the simplest sCI, formaldehyde oxide, CH2OO, and its bimolecular reaction with the water monomer have been experimentally determined at T = (297 +/- 1) K and at atmospheric pressure by using a free-jet flow system. CH2OO was produced by the reaction of ozone with C2H4, and CH2OO concentrations were probed indirectly by detecting H2SO4 after titration with SO2. Time-resolved experiments yield a rate coefficient of the unimolecular reaction of k(uni) = (0.19 +/- 0.07) s(-1), a value that is supported by quantum-chemical and statistical rate theory calculations as well as by additional measurements performed under CH2OO steady state conditions. A rate coefficient of k(CH2OO+H2O) = (3.2 +/- 1.2) * 10(-16) cm(3) molecule(-1) s(-1) has been determined for sufficiently low H2O concentrations (<10(15) molecule cm(-3)) that allow separation from the CH2OO reaction with the water dimer. In order to evaluate the accuracy of the experimental approach, the rate coefficients of the reactions with acetaldehyde and acetone were reinvestigated. The obtained rate coefficients k(CH2OO+acetald) = (1.7 +/- 0.5) * 10(-12) and k(CH2OO+acetone) = (3.4 +/- 0.9) * 10(-13) cm(3) molecule(-1) s(-1) are in good agreement with literature data. PMID- 26159710 TI - Sun Safety at Work Canada: a multiple case-study protocol to develop sun safety and heat protection programs and policies for outdoor workers. AB - BACKGROUND: CAREX Canada has identified solar ultraviolet radiation (UV) as the second most prominent carcinogenic exposure in Canada, and over 75 % of Canadian outdoor workers fall within the highest exposure category. Heat stress also presents an important public health issue, particularly for outdoor workers. The most serious form of heat stress is heat stroke, which can cause irreversible damage to the heart, lungs, kidneys, and liver. Although the need for sun and heat protection has been identified, there is no Canada-wide heat and sun safety program for outdoor workers. Further, no prevention programs have addressed both skin cancer prevention and heat stress in an integrated approach. The aim of this partnered study is to evaluate whether a multi-implementation, multi-evaluation approach can help develop sustainable workplace-specific programs, policies, and procedures to increase the use of UV safety and heat protection. METHODS/DESIGN: This 2-year study is a theory-driven, multi-site, non-randomized study design with a cross-case analysis of 13 workplaces across four provinces in Canada. The first phase of the study includes the development of workplace-specific programs with the support of the intensive engagement of knowledge brokers. There will be a three-points-in-time evaluation with process and impact components involving the occupational health and safety (OHS) director, management, and workers with the goal of measuring changes in workplace policies, procedures, and practices. It will use mixed methods involving semi-structured key informant interviews, focus groups, surveys, site observations, and UV dosimetry assessment. Using the findings from phase I, in phase 2, a web-based, interactive, intervention planning tool for workplaces will be developed, as will the intensive engagement of intermediaries such as industry decision-makers to link to policymakers about the importance of heat and sun safety for outdoor workers. DISCUSSION: Solar UV and heat are both health and safety hazards. Using an occupational health and safety risk assessment and control framework, Sun Safety at Work Canada will support workplaces to assess their exposure risks, implement control strategies that build on their existing programs, and embed the controls into their existing occupational health and safety system. PMID- 26159711 TI - Fueling the Fire with Fibers: Bacterial Amyloids Promote Inflammatory Disorders. AB - Bacterial infection is associated with increased morbidity in patients with systematic lupus erythematosus. In a recent Immunity paper, Gallo et al. (2015) report that extracellular DNA is bound tightly by bacterial amyloid fibrils during biofilm formation and that amyloid/DNA composites are immune stimulators when injected into mice, leading to autoimmunity. PMID- 26159712 TI - Macrophage Supply and Demand at the Core of the Necrotic Granuloma. AB - Central necrosis of granulomas is linked to progression of major diseases, including tuberculosis and atherosclerosis. In this issue of Cell Host & Microbe, Pagan et al. (2015) reveal that necrotic granulomas develop when macrophage supply is insufficient. These findings suggest augmenting macrophage availability as a therapeutic strategy in tuberculosis. PMID- 26159713 TI - The Bug Stops Here: Innate Lymphoid Cells in Clostridium difficile Infection. AB - The contribution of the innate immune response to the resolution of Clostridium difficile infection (CDI) remains incompletely defined. In this issue of Cell Host & Microbe, Abt et al. demonstrated that innate lymphoid cells and the effector cytokine IFN-gamma are important for recovery from the acute phase of CDI. PMID- 26159715 TI - Calcium Builds Strong Host-Parasite Interactions. AB - Apicomplexan parasite invasion of host cells is a multistep process, requiring coordinated events. In this issue of Cell Host & Microbe, Paul et al. (2015) and Philip and Waters (2015) leverage experimental genetics to show that the calcium regulated protein phosphatase, calcinuerin, regulates invasion in multiple parasite species. PMID- 26159714 TI - Bacterial Reductionism: Host Thiols Enhance Virulence. AB - Intracellular bacteria exploit host cytosolic signals to upregulate virulence genes. In this issue of Cell Host & Microbe, Wong et al. (2015) show that Burkholderia pseudomallei senses host cytosolic glutathione, a low-molecular weight thiol, through the membrane-bound histidine sensor kinase VirA, highlighting the importance of inter-kingdom signaling in bacterial pathogenesis. PMID- 26159716 TI - Expanding the Molecular Toolkit for Chlamydia. AB - Although historically a genetically intractable bacterium, Chlamydia is experiencing a renaissance for molecular genetic manipulation. Two new studies published in Cell Host & Microbe, Mirrashidi et al. (2015) and Kokes et al. (2015), have dramatically changed the landscape of what is possible for molecular dissection of Chlamydia-host interactions. PMID- 26159717 TI - Myeloid Growth Factors Promote Resistance to Mycobacterial Infection by Curtailing Granuloma Necrosis through Macrophage Replenishment. AB - The mycobacterial ESX-1 virulence locus accelerates macrophage recruitment to the forming tuberculous granuloma. Newly recruited macrophages phagocytose previously infected apoptotic macrophages to become new bacterial growth niches. Granuloma macrophages can then necrose, releasing mycobacteria into the extracellular milieu, which potentiates their growth even further. Using zebrafish with genetic or pharmacologically induced macrophage deficiencies, we find that global macrophage deficits increase susceptibility to mycobacterial infection by accelerating granuloma necrosis. This is because reduction in the macrophage supply below a critical threshold decreases granuloma macrophage replenishment to the point where apoptotic infected macrophages, failing to get engulfed, necrose. Reducing macrophage demand by removing bacterial ESX-1 offsets the susceptibility of macrophage deficits. Conversely, increasing macrophage supply in wild-type fish by overexpressing myeloid growth factors induces resistance by curtailing necrosis. These findings may explain the susceptibility of humans with mononuclear cytopenias to mycobacterial infections and highlight the therapeutic potential of myeloid growth factors in tuberculosis. PMID- 26159718 TI - Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection. AB - Infection with the opportunistic enteric pathogen Clostridium difficile is an increasingly common clinical complication that follows antibiotic treatment induced gut microbiota perturbation. Innate lymphoid cells (ILCs) are early responders to enteric pathogens; however, their role during C. difficile infection is undefined. To identify immune pathways that mediate recovery from C. difficile infection, we challenged C57BL/6, Rag1(-/-) (which lack T and B cells), and Rag2(-/-)Il2rg(-/-) (Raggammac(-/-)) mice (which additionally lack ILCs) with C. difficile. In contrast to Rag1(-/-) mice, ILC-deficient Raggammac(-/-) mice rapidly succumbed to infection. Rag1(-/-) but not Raggammac(-/-) mice upregulate expression of ILC1- or ILC3-associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Raggammac(-/ ) mice. While ILC3s made a minor contribution to resistance, loss of IFN-gamma or T-bet-expressing ILC1s in Rag1(-/-) mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile. PMID- 26159720 TI - Co-option of Membrane Wounding Enables Virus Penetration into Cells. AB - During cell entry, non-enveloped viruses undergo partial uncoating to expose membrane lytic proteins for gaining access to the cytoplasm. We report that adenovirus uses membrane piercing to induce and hijack cellular wound removal processes that facilitate further membrane disruption and infection. Incoming adenovirus stimulates calcium influx and lysosomal exocytosis, a membrane repair mechanism resulting in release of acid sphingomyelinase (ASMase) and degradation of sphingomyelin to ceramide lipids in the plasma membrane. Lysosomal exocytosis is triggered by small plasma membrane lesions induced by the viral membrane lytic protein-VI, which is exposed upon mechanical cues from virus receptors, followed by virus endocytosis into leaky endosomes. Chemical inhibition or RNA interference of ASMase slows virus endocytosis, inhibits virus escape to the cytosol, and reduces infection. Ceramide enhances binding of protein-VI to lipid membranes and protein-VI-induced membrane rupture. Thus, adenovirus uses a positive feedback loop between virus uncoating and lipid signaling for efficient membrane penetration. PMID- 26159719 TI - Flavivirus Antagonism of Type I Interferon Signaling Reveals Prolidase as a Regulator of IFNAR1 Surface Expression. AB - Type I interferon (IFN-alpha/beta or IFN-I) signals through two receptor subunits, IFNAR1 and IFNAR2, to orchestrate sterile and infectious immunity. Cellular pathways that regulate IFNAR1 are often targeted by viruses to suppress the antiviral effects of IFN-I. Here we report that encephalitic flaviviruses, including tick-borne encephalitis virus and West Nile virus, antagonize IFN-I signaling by inhibiting IFNAR1 surface expression. Loss of IFNAR1 was associated with binding of the viral IFN-I antagonist, NS5, to prolidase (PEPD), a cellular dipeptidase implicated in primary immune deficiencies in humans. Prolidase was required for IFNAR1 maturation and accumulation, activation of IFNbeta-stimulated gene induction, and IFN-I-dependent viral control. Human fibroblasts derived from patients with genetic prolidase deficiency exhibited decreased IFNAR1 surface expression and reduced IFNbeta-stimulated signaling. Thus, by understanding flavivirus IFN-I antagonism, prolidase is revealed as a central regulator of IFN I responses. PMID- 26159721 TI - Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus. AB - Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure-based vaccine development. PMID- 26159722 TI - In vitro evaluation and comparison of 5 rapid antigen detection tests for the diagnosis of beta-hemolytic group A streptococcal pharyngitis. AB - Streptococcus pyogenes (group A Streptococcus [GAS]) is the leading cause of bacterial pharyngitis. To perform a rapid diagnosis of GAS pharyngitis, rapid antigen detection tests (RADTs) have been developed. In this study, we evaluated and compared the sensitivity and specificity of 5 RADTs (bioNexia Strep A plusTM, bioNexia Strep A dipstickTM, Clearview Strep ATM, QuickVue Strep A plusTM, and StreptatestTM), using analytical approaches combining dilutions in NaCl 0.9% or in pharyngeal flora. The practicability of each RADT was also determined. Among the 630 RADTs performed in this work, all were specific, as no false positive was found resulting in a specificity of 100%. The 5 RADTs detected GAS at 10(6)CFU/mL in NaCl 0.9% or pooled pharyngeal flora. Regarding the practicability analysis, bioNexia Strep A plus, bioNexia Strep A dipstick and Streptatest RADTs obtained the highest scores for secondary items including kit content and instructions for use information. We concluded that these 5 easy-to-use RADTs are suitable for diagnosis of GAS pharyngitis, as they all detect GAS at a concentration commonly found during pharyngitis. PMID- 26159725 TI - [Hyponatremia, alcohol and ataxia]. PMID- 26159726 TI - [Asthenia and chronic joint pain in a 73-year-old woman]. PMID- 26159727 TI - Heavy metal spatial variability and historical changes in the Yangtze River estuary and North Jiangsu tidal flat. AB - This research focuses on the spatial and temporal patterns of heavy metals from the Yangtze River estuary and the tidal flat of north Jiangsu. Most heavy metals in the surficial sediments after normalization to Ti decreased seaward at the Yangtze River estuary. The core records showed that the heavy metal variations in the last 50years were primarily linked to natural weathering input of trace elements. However, significant heavy metal pollution (mainly Ni, Pb, Cd, Cu and As) were in the two study areas, with anthropogenic inventories accounting for 23 40% percent of the total pollution. Sequential extraction showed that Pb, Cu and Ni were present largely in the non-residual fraction, which indicated the potential bioavailability in the study areas. The SEM/EDS together with sequential extraction facilitated the easy tracing of the origin/sources of heavy metals in a simple way in the estuary and the tidal flat. PMID- 26159723 TI - Co-targeting of Cyclooxygenase-2 and FoxM1 is a viable strategy in inducing anticancer effects in colorectal cancer cells. AB - BACKGROUND: Cross-talk between deregulated signaling pathways in cancer cells causes uncontrolled growth and proliferation. These cancers cells become more aggressive and quickly develop resistance to therapy. Therefore targeting of these deregulated pathways simultaneously can result in efficient cell death of cancer cells. In this study we investigated co-expression of Cox-2 and FoxM1 in a cohort of colorectal carcinoma (CRC) samples and also examined whether inhibition of Cox-2 and FoxM1 simultaneously can lead to inhibition of cell viability and induction of apoptosis in colorectal cancer cell lines and in vivo xenografts. METHODS: Protein expression of Cox-2 and FoxM1 was determined in a large cohort of 770 clinical CRC samples in a tissue micro-array format by immunohistochemistry. Cell death was measured using live dead assay. Apoptosis was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Calcusyn software was utilized to estimate the synergistic doses using chou and Talalay method. RESULTS: Co-expression of Cox-2 and FoxM1 was detected in 33.3 % (232/697) of CRC's and associated with an aggressive phenotype characterized by younger age (p = 0.0191), high proliferative index marker; Ki-67 (p = 0.004) and MMP-9 (p = 0.0116) as well as activation of AKT (p = 0.0214). In vitro, inhibition of FoxM1 and Cox-2 with pharmacological inhibitors; Thiostrepton and NS398 resulted in efficient down regulation of FoxM1 and Cox-2 expression along with in-activation of AKT and inhibition of colony formation, invasion and migratory capability of CRC cells. In addition, there was also inhibition of cell viability and induction of apoptosis via the mitochondrial apoptotic pathway in CRC cell lines. Finally, treatment of CRC xenograft tumors in nude mice with combination of Cox-2 and FoxM1 inhibitors inhibited tumor growth significantly via down-regulation of Cox 2 and FoxM1 expression. CONCLUSIONS: These findings demonstrate that co expression of Cox-2 and FoxM1 might play a critical role in the pathogenesis of CRC. Therefore, targeting of these pathways simultaneously with sub toxic doses of pharmacological inhibitors can be a potential therapeutic approach for the treatment of this subset of CRC. PMID- 26159724 TI - Transcriptome sequencing of microglial cells stimulated with TLR3 and TLR4 ligands. AB - BACKGROUND: Resident macrophages in the CNS microglia become activated and produce proinflammatory molecules upon encountering bacteria or viruses. TLRs are a phylogenetically conserved diverse family of sensors that drive innate immune responses following interactions with PAMPs. TLR3 and TLR4 recognize viral dsRNA Poly (I:C) and bacterial endotoxin LPS, respectively. Importantly, these receptors differ in their downstream adaptor molecules. Thus far, only a few studies have investigated the effects of TLR3 and TLR4 in macrophages. However, a genome-wide search for the effects of these TLRs has not been performed in microglia using RNA-seq. Gene expression patterns were determined for the BV-2 microglial cell line when stimulated with viral dsRNA Poly (I:C) or bacterial endotoxin LPS to identify novel transcribed genes, as well as investigate how differences in downstream signaling could influence gene expression in innate immunity. RESULTS: Sequencing assessment and quality evaluation revealed that common and unique patterns of proinflammatory genes were significantly up regulated in response to TLR3 and TLR4 stimulation. However, the IFN/viral response gene showed a stronger response to TLR3 stimulation than to TLR4 stimulation. Unexpectedly, TLR3 and TLR4 stimulation did not activate IFN-beta and IRF3 in BV-2 microglia. Most importantly, we observed that previously unidentified transcription factors (TFs) (i.e., IRF1, IRF7, and IRF9) and the epigenetic regulators KDM4A and DNMT3L were significantly up-regulated in both TLR3- and TLR4-stimulated microglia. We also identified 29 previously unidentified genes that are important in immune regulation. In addition, we confirmed the expressions of key inflammatory genes as well as pro-inflammatory mediators in the supernatants were significantly induced in TLR3-and TLR4 stimulated primary microglial cells. Moreover, transcriptional start sites (TSSs) and isoforms, as well as differential promoter usage, revealed a complex pattern of transcriptional and post-transcriptional gene regulation upon infection with TLR3 and TLR4. Furthermore, TF motif analysis (-950 to +50 bp of the 5' upstream promoters) revealed that the DNA sequences for NF-kappaB, IRF1, and STAT1 were significantly enriched in TLR3- and TLR4-stimulated microglia. CONCLUSIONS: These unprecedented findings not only permit a comparison of TLR3-and TLR4-stimulated genes but also identify new genes that have not been previously implicated in innate immunity. PMID- 26159729 TI - Network analysis for a network disorder: The emerging role of graph theory in the study of epilepsy. AB - Recent years have witnessed a paradigm shift in the study and conceptualization of epilepsy, which is increasingly understood as a network-level disorder. An emblematic case is temporal lobe epilepsy (TLE), the most common drug-resistant epilepsy that is electroclinically defined as a focal epilepsy and pathologically associated with hippocampal sclerosis. In this review, we will summarize histopathological, electrophysiological, and neuroimaging evidence supporting the concept that the substrate of TLE is not limited to the hippocampus alone, but rather is broadly distributed across multiple brain regions and interconnecting white matter pathways. We will introduce basic concepts of graph theory, a formalism to quantify topological properties of complex systems that has recently been widely applied to study networks derived from brain imaging and electrophysiology. We will discuss converging graph theoretical evidence indicating that networks in TLE show marked shifts in their overall topology, providing insight into the neurobiology of TLE as a network-level disorder. Our review will conclude by discussing methodological challenges and future clinical applications of this powerful analytical approach. PMID- 26159728 TI - Prospective cohort study of the relationship between neuro-cognition, social cognition and violence in forensic patients with schizophrenia and schizoaffective disorder. AB - BACKGROUND: There is a broad literature suggesting that cognitive difficulties are associated with violence across a variety of groups. Although neurocognitive and social cognitive deficits are core features of schizophrenia, evidence of a relationship between cognitive impairments and violence within this patient population has been mixed. METHODS: We prospectively examined whether neurocognition and social cognition predicted inpatient violence amongst patients with schizophrenia and schizoaffective disorder (n = 89; 10 violent) over a 12 month period. Neurocognition and social cognition were assessed using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Using multivariate analysis neurocognition and social cognition variables could account for 34 % of the variance in violent incidents after controlling for age and gender. Scores on a social cognitive reasoning task (MSCEIT) were significantly lower for the violent compared to nonviolent group and produced the largest effect size. Mediation analysis showed that the relationship between neurocognition and violence was completely mediated by each of the following variables independently: social cognition (MSCEIT), symptoms (PANSS Total Score), social functioning (SOFAS) and violence proneness (HCR-20 Total Score). There was no evidence of a serial pathway between neurocognition and multiple mediators and violence, and only social cognition and violence proneness operated in parallel as significant mediators accounting for 46 % of the variance in violent incidents. There was also no evidence that neurocogniton mediated the relationship between any of these variables and violence. CONCLUSIONS: Of all the predictors examined, neurocognition was the only variable whose effects on violence consistently showed evidence of mediation. Neurocognition operates as a distal risk factor mediated through more proximal factors. Social cognition in contrast has a direct effect on violence independent of neurocognition, violence proneness and symptom severity. The neurocognitive impairment experienced by patients with schizophrenia spectrum disorders may create the foundation for the emergence of a range of risk factors for violence including deficits in social reasoning, symptoms, social functioning, and HCR-20 risk items, which in turn are causally related to violence. PMID- 26159730 TI - Chikungunya virus pathogenesis: From bedside to bench. AB - Chikungunya virus (CHIKV) is an arbovirus transmitted to humans by mosquito bite. A decade ago, the virus caused a major outbreak in the islands of the Indian Ocean, then reached India and Southeast Asia. More recently, CHIKV has emerged in the Americas, first reaching the Caribbean and now extending to Central, South and North America. It is therefore considered a major public health and economic threat. CHIKV causes febrile illness typically associated with debilitating joint pains. In rare cases, it may also cause central nervous system disease, notably in neonates. Joint symptoms may persist for months to years, and lead to arthritis. This review focuses on the spectrum of signs and symptoms associated with CHIKV infection in humans. It also illustrates how the analysis of clinical and biological data from human cohorts and the development of animal and cellular models of infection has helped to identify the tissue and cell tropisms of the virus and to decipher host responses in benign, severe or persistent disease. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World". PMID- 26159731 TI - Towards basic ionic liquid-based hybrid membranes as hydroxide-conducting electrolytes under low humidity conditions. AB - We have developed basic ionic liquid-based hybrid membranes with ionic liquid modified zeolitic imidazolate frameworks (ZIFs) as fillers, aiming to enhance the electrochemical and physical properties of the membrane. PMID- 26159732 TI - Safety Strategy Use Among Women Seeking Temporary Protective Orders: The Relationship Between Violence Experienced, Strategy Effectiveness, and Risk Perception. AB - This study examined safety strategy use in relation to intimate partner violence (IPV) victimization, perceived effectiveness of the strategies, and perception of danger from IPV among 197 abused women. More than 90% of the women used 1 or more strategies in the 6 months prior to their interview. Severe physical and sexual violence were significantly associated with an increased use of placating strategies. Perceived effectiveness of the strategies was high yet not associated with strategy use. Increased perception of danger from IPV was significantly associated with increased use of safety planning strategies. The findings suggest that safety planning should be tailored to fit women's specific contexts. Safety planning discussions should focus on strategies that reduce women's risk of continued violence and build on women's strengths. PMID- 26159733 TI - Robust hematopoietic progenitor cell commitment in the presence of a conflicting cue. AB - Hematopoietic lineage commitment is regulated by cytokines and master transcription factors, but it remains unclear how a progenitor cell chooses a lineage in the face of conflicting cues. Through transcript counting in megakaryocyte-erythroid progenitors undergoing erythropoiesis, we show that the expression levels of the pro-erythropoiesis transcription factor EKLF (also known as KLF1) and receptor EpoR are inversely correlated with their pro megakaryopoiesis counterparts, FLI-1 and TpoR (also known as MPL). Notably, as progenitors commit to the erythrocyte lineage, EpoR is upregulated and TpoR is strongly downregulated, thus boosting the potency of the pro-erythropoiesis cue erythropoietin and effectively eliminating the activity of the pro megakaryopoiesis cue thrombopoietin. Based on these findings, we propose a new model for exclusive decision making that explicitly incorporates signals from extrinsic cues, and we experimentally confirm a model prediction of temporal changes in transcript noise levels in committing progenitors. Our study suggests that lineage-specific receptor levels can modulate potencies of cues to achieve robust commitment decisions. PMID- 26159734 TI - The prion protein inhibits monocytic cell migration by stimulating beta1 integrin adhesion and uropod formation. AB - The broad tissue distribution and evolutionary conservation of the glycosylphosphatidylinositol (GPI)-anchored prion protein (PrP, also known as PRNP) suggests that it plays a role in cellular homeostasis. Given that integrin adhesion determines cell behavior, the proposed role of PrP in cell adhesion might underlie the various in vitro and in vivo effects associated with PrP loss of-function, including the immune phenotypes described in PrP(-/-) mice. Here, we investigated the role of PrP in the adhesion and (transendothelial) migration of human (pro)monocytes. We found that PrP regulates beta1-integrin-mediated adhesion of monocytes. Additionally, PrP controls the cell morphology and migratory behavior of monocytes: PrP-silenced cells show deficient uropod formation on immobilized VCAM and display bleb-like protrusions on the endothelium. Our data further show that PrP regulates ligand-induced integrin activation. Finally, we found that PrP controls the activation of several proteins involved in cell adhesion and migration, including RhoA and its effector cofilin, as well as proteins of the ERM family. We propose that PrP modulates beta1 integrin adhesion and migration of monocytes through RhoA-induced actin remodeling mediated by cofilin, and through the regulation of ERM-mediated membrane-cytoskeleton linkage. PMID- 26159735 TI - Caveolae - mechanosensitive membrane invaginations linked to actin filaments. AB - An essential property of the plasma membrane of mammalian cells is its plasticity, which is required for sensing and transmitting of signals, and for accommodating the tensional changes imposed by its environment or its own biomechanics. Caveolae are unique invaginated membrane nanodomains that play a major role in organizing signaling, lipid homeostasis and adaptation to membrane tension. Caveolae are frequently associated with stress fibers, a major regulator of membrane tension and cell shape. In this Commentary, we discuss recent studies that have provided new insights into the function of caveolae and have shown that trafficking and organization of caveolae are tightly regulated by stress-fiber regulators, providing a functional link between caveolae and stress fibers. Furthermore, the tension in the plasma membrane determines the curvature of caveolae because they flatten at high tension and invaginate at low tension, thus providing a tension-buffering system. Caveolae also regulate multiple cellular pathways, including RhoA-driven actomyosin contractility and other mechanosensitive pathways, suggesting that caveolae could couple mechanotransduction pathways to actin-controlled changes in tension through their association with stress fibers. Therefore, we argue here that the association of caveolae with stress fibers could provide an important strategy for cells to deal with mechanical stress. PMID- 26159736 TI - Influence of W, Mo and Ti trace elements on the phase separation in Al8Co17Cr17Cu8Fe17Ni33 based high entropy alloy. AB - Compositionally complex alloys, also called high entropy alloys, have been investigated for over a decade in view of different applications, but so far only a small number of alloys can be considered as presenting good enough properties for industrial application. The most common family of elements is Al-Co-Cr-Cu-Fe Ni. The equiatomic alloy having 5 phases and being too brittle, the composition has been modified in order to improve the mechanical properties. Different compositions have been tested and as a first result ductile Al8Co17Cr17Cu8Fe17Ni33 has been chosen for deeper investigation. It shows a dendritic segregation into Co-Cr-Fe rich cores and Al-Cu-Ni rich interdendritic sites. The as-cast state is characterized mainly by two phases, namely Al-Cu-Ni rich precipitates of L12 structure inside a solid solution matrix. After homogenization both alloys consists of a single solid solution phase. Results are compared to calculations by ThermoCalc. In order to further improve the properties of the alloy the Cr content has been decreased and replaced by trace elements W, Mo and Ti, which, according to ThermoCalc, increase the melting point and the phase transition temperature which leads to the formation of the L12 phase. As-cast and heat treated samples of the base and the modified alloy have been investigated by transmission electron microscopy and three dimensional atom probe. Results of the investigations will be discussed in terms of microstructure, hardness and coherence with Thermo Calc predictions. PMID- 26159737 TI - Development of tyrosinase biosensor based on quantum dots/chitosan nanocomposite for detection of phenolic compounds. AB - A sensitive and simple amperometric biosensor for phenols was developed based on the immobilization of tyrosinase into CdS quantum dots/chitosan nanocomposite matrix. The nanocomposite film with porous nanostructure, excellent hydrophilicity and biocompatibility resulted in high enzyme loading, and the tyrosinase (Tyr) immobilized in this novel matrix retained its activity to a large extent. The CdS quantum dots/chitosan nanocomposite film was characterized by scanning electron microscopy and electrochemical impedance spectroscopy, and the parameters of the various experimental variables for the biosensor were optimized. Under the optimal conditions, the designed biosensor displayed a wide linear response to catechol over a concentration range of 1.0*10(-9) to 2.0*10( 5)M with a high sensitivity of 561+/-9.7mAM(-1) and a low detection limit down to 0.3 nM at a signal-to-noise ratio of 3. The CdS quantum dots/chitosan nanocomposites could provide a novel matrix for enzyme immobilization to promote the development of biosensing and biocatalysis. PMID- 26159738 TI - Photostability evaluation of five UV-filters, trans-resveratrol and beta-carotene in sunscreens. AB - Trans-resveratrol (RES) is used in cosmetic formulations and beta-carotene (BTC) is a classical sunscreen antioxidant, but their photostability in sunscreens, a property directly correlated to performance and safety has not been addressed in the literature. This paper reports the assessment of RES and/or BTC influence on the photostability of five UV-filters (octyl methoxycinnamate - OMC, avobenzone AVO, octocrylene - OCT, bemotrizinole - BMZ, octyltriazone - OTZ) in three different combinations after UVA exposure followed by the identification of degradation products and the assessment of photoreactivity. The evaluation of sunscreen photostability was performed by HPLC and spectrophotometric analysis, and degradation products were identified by GC-MS analysis. Components RES, BTC, OMC and AVO were significantly degraded after UV exposure (reduction of around 16% in recovery). According to HPLC analysis, all formulations presented similar photostability profiles. Eleven degradation products were identified in GC-MS analysis, among them products of RES, BTC, OMC and AVO photodegradation. All evaluated formulations were considered photoreactive, as well as the isolated compounds RES and AVO. Considering HPLC, spectrophotometric and GC-MS results, it is suggested that formulations containing BMZ were considered the most photostable. The combination RES+BTC in a sunscreen improved the photostability of AVO. The benefits of using a combination of antioxidants in sunscreens was demonstrated by showing that using RES+BTC+studied UV-filters led to more photostable formulations, which in turn implies in better safety and efficacy. PMID- 26159739 TI - Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems. AB - Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH sensitivity. The liposomes were characterized by DLS, zeta-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL 60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells. PMID- 26159740 TI - The E3 Ubiquitin Ligase COP1 Regulates Thermosensory Flowering by Triggering GI Degradation in Arabidopsis. AB - Floral transition is influenced by environmental factors such as light and temperature. Plants are capable of integrating photoperiod and ambient temperature signaling into their developmental program. Despite extensive investigations on individual genetic pathways, little is known about the molecular components that integrate both pathways. Here, we demonstrate that the RING finger-containing E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) acts as an integrator of photoperiod and ambient temperature signaling. In addition to the role in photoperiodic destabilization of CONSTANS (CO), COP1 also regulates temperature sensitivity by controlling the degradation of GIGANTEA (GI). COP1-impaired mutants showed reduced sensitivity to low ambient temperature. Notably, COP1 is more stabilized at low temperature and accelerates GI turnover in a 26S proteasome-dependent manner. The direct association of GI with the promoter of FLOWERING LOCUS T (FT) was reduced because of its ambient temperature-dependent protein stability control, and thus COP1-triggered GI turnover delays flowering at low temperatures via a CO-independent pathway. Taken together, our findings indicate that environmental conditions regulate the stability of COP1, and conditional specificity of its target selection stimulates proper developmental responses and ensures reproductive success. PMID- 26159742 TI - Drug interactions of hepatitis C direct-acting antivirals in the HIV-infected person. AB - The development of direct-acting antivirals for hepatitis C has occurred at a rapid pace. Up to recently, HCV therapy has been limited to pegylated-interferon and ribavirin, but now physicians have several highly efficacious and well tolerated interferon-free direct-acting antiviral agent (DAA) regimens available. In order to minimise patient harm and maximise the response to therapy, physicians must remain cognisant of the potential DAA drug-drug interactions in patients with HIV/HCV co-infection. HCV clearance needs to be achieved while maintaining HIV suppression and not compromising future antiretroviral options. CYP450 enzyme induction or inhibition accounts for many of the pharmacokinetic interactions between HCV DAA and HIV antiretrovirals, although an increasing number of transporter-mediated interactions are now recognised. DAA interactions in the HIV/HCV co-infected patient are largely extrapolated from drug-drug interaction studies with commonly used antiretrovirals. These studies then inform the selection of permitted antiretroviral regimens in phase II and III DAA clinical studies in HIV/HCV co-infection. We review the recently reported drug drug interaction studies of HCV DAA therapy in the HIV-infected person and the HIV antiretroviral combinations in HCV DAA clinical trials. PMID- 26159743 TI - A 6-Year Single-Center Experience of Intra-aortic Balloon Pump Treatment- Retrospective Analysis of 223 Patients. AB - OBJECTIVES: This study describes the long-term survival (1 year) of patients after intra-aortic balloon pump (IAPB) treatment. DESIGN: A single-center, retrospective registry study. SETTING: Single university hospital intensive care unit. PARTICIPANTS: Participants included 223 consecutive patients who received intra-aortic balloon pump (IABP) treatment between January 1, 2005, and December 31, 2010 (203 cardiac surgical patients [7.8% of all cardiac surgical patients] and 20 conservative medical patients). INTERVENTIONS: IABP treatment was used as an adjunct therapy for severe hemodynamic compromise perioperatively in cardiac surgery and in hemodynamic shock of other etiology. MEASUREMENTS AND MAIN RESULTS: Mean age of patients was 66+/-10 years. The 30-day mortality was 22.1% for surgical patients and 37.8% for conservative medical patients. The 1-year mortality was 24.5% for surgical patients and 55% for conservative medical patients. There were 14 (6.3%) major complications related to IABP treatment that required operative treatment. The 1-year survival for patients surviving the initial 30 days after coronary artery bypass grafting was 95.2%. Independent predictors of 1-year mortality (Cox regression) were age, previous cardiac surgery, critical preoperative state, and conservative medical treatment. Timing (preoperative, intraoperative, postoperative) of IABP treatment did not predict survival. CONCLUSIONS: IABP treatment was safe with few serious complications. Timing of IABP placement was not related to survival. Survival at 1-year follow up was excellent after an initially high mortality for cardiac surgical patients treated for hemodynamic compromise with aortic counterpulsation. PMID- 26159741 TI - Adverse pregnancy outcomes and cardiovascular risk factor management. AB - Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman's risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1 year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID- 26159744 TI - CASE 10-2015: Cardiac Resynchronization Therapy: Role of Intraoperative Real-Time Three-Dimensional Transesophageal Echocardiography. PMID- 26159745 TI - Vascular Surgery Kidney Injury Predictive Score: A Historical Cohort Study. AB - OBJECTIVES: To develop a risk-prediction model for acute kidney injury (AKI) in patients undergoing vascular surgery. DESIGN: A retrospective cohort study. SETTING: A tertiary referral center. PARTICIPANTS: Participants included 845 adult patients who underwent vascular surgery between January 3, 2003, and May 29, 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median age of patients was 72 years (interquartile range 65-80 years), and 653 patients (77%) were male. AKI developed in 258 (30.5%) patients. Patients with AKI had lower estimated glomerular filtration rates (60+/-21 v 72+/-21, p<0.001), were older (73 [68-78] years v 71 [65-80] years, p = 0.01), had a higher prevalence of hypertension (81% v 73%, p = 0.02), and were more likely to undergo emergency surgery (5% v 2%, p = 0.02). Patients with AKI also received more diuretics (p<0.001) and beta-blockers (p = 0.003) prior to surgery. The multivariate AKI risk-prediction model with preoperative variables (estimated glomerular filtration rate, previous vascular interventions, use of preoperative diuretics and beta-blockers, and emergency surgery) showed an area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.628-0.710); a model with additional intraoperative variables (procedure duration, fluid balance, and plasma and platelet transfusion) had an area under the receiver operating characteristic curve of 0.72 (95% confidence interval, 0.685-0.760). CONCLUSIONS: As AKI is a very common complication after vascular surgery, a risk prediction model was derived to assess the likelihood of postoperative AKI. If validated in an independent cohort, this model may be used to facilitate targeted interventions in vascular surgery patients at high risk for AKI. PMID- 26159746 TI - Reversal of IL-13-induced inflammation and Ca(2+) sensitivity by resolvin and MAG DHA in association with ASA in human bronchi. AB - The aim of this study was to investigate the effects of resolvin D1 (RvD1), as well as the combined treatment of docosahexaenoic acid monoglyceride (MAG-DHA) and acetylsalicylic acid (ASA), on the resolution of inflammation markers and Ca(2+) sensitivity in IL-13-pretreated human bronchi (HB). Tension measurements performed with 300 nM RvD1 largely abolished (50%) the over-reactivity triggered by 10 ng/ml IL-13 pretreatment and reversed hyper Ca(2+) sensitivity. Addition of 300 nM 17(S)-HpDoHE, the metabolic intermediate between DHA and RvD1, displayed similar effects. In the presence of 100 MUM ASA (a COX inhibitor), the inhibitory effect of 1 MUM MAG-DHA on muscarinic tone was further amplified, but not in the presence of Ibuprofen. Western blot analysis revealed that the combined treatment of MAG-DHA and ASA upregulated GPR-32 expression and downregulated cytosolic TNFalpha detection, hence preventing IkappaBalpha degradation and p65-NFkappaB phosphorylation. The Ca(2+) sensitivity of HB was also quantified on beta-escin permeabilized preparations. The presence of ASA potentiated the inhibitory effects of MAG-DHA in reducing the Ca(2+) hypersensitivity triggered by IL-13 by decreasing the phosphorylation levels of the PKC-potentiated inhibitor protein-17 regulatory protein (CPI-17). In summary, MAG-DHA combined with ASA, as well as exogenously added RvD1, may represent valuable assets against critical AHR disorder. PMID- 26159748 TI - Reflections on a Research Clerkship Abroad. PMID- 26159749 TI - Knowledge of Primary Care Physicians About Breast-Cancer-Related Lymphedema: Turkish Perspective. AB - Breast-cancer-related lymphedema (BCRL) is a common complication of breast cancer treatment. Informing patients about BCRL can contribute to decrease their risk of developing the condition or prevent it from progressing further. In order to educate patients about BCRL effectively, clinical knowledge of clinicians must be adequate. In study, we aimed to reflect BCRL knowledge and attitude of Turkish primary care physicians (PCPs). This questionnaire-based study was conducted by face-to-face interview method. The participants included actively working PCPs from all parts of Turkey. The questionnaire elicited data on physicians' demographics, the BCRL knowledge, self-reported BCRL knowledge, referral patterns, and education. A total of 314 PCPs with a mean age of 36.9 % +/- 8.1 years (mean +/- standard deviation) were included in the study. Median BCRL knowledge score of all study group was 15 (11-18) [median (25-75 % range)]. PCPs who received education about BCRL during their medical faculty and/or residency periods had significantly higher knowledge scores (p = 0.005). Of PCPs, 94.9 % indicated to make a BCRL referral for a breast cancer patient. Among them, 55 % preferred to make a referral to a general surgeon, 28.2 % to an oncologist, and 16.8 % to a physical medicine and rehabilitation specialist. Assessment of factors related with BCRL should be part of routine evaluation of patients with breast cancer in primary care. Education of PCPs about BCRL is warranted in order to improve the BCRL care. PMID- 26159747 TI - Non-Linear Heart Rate Variability Indices in the Frequent Hemodialysis Network Trials of Chronic Hemodialysis Patients. AB - BACKGROUND: Non-linear heart rate variability (HRV) indices were hypothesized to correlate with cardiac function, fluid overload and physical performance in hemodialysis patients. METHODS: Twenty-four-hour Holter electrocardiograms were recorded in patients enrolled in the Frequent Hemodialysis Network (FHN) Daily Dialysis Trial. Correlations between non-linear HRV indices and left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), extracellular volume (ECV)/total body water (TBW) ratio, the SF-36 Physical Health Composite (PHC) and Physical Functioning (PF) scores were tested. RESULTS: We studied 210 subjects (average age 49.8 +/- 13.5 years, 62% men, 42% diabetics). In non-diabetic patients, multiscale entropy (MSE) slope sample entropy (SampEn) and approximate entropy (ApEn) correlated positively with LVEF, PF and PHC and inversely with LVEDV and ECV/TBW. Spectral power slope correlated positively with ECV/TBW (r = 0.27). Irregularity measures (MSE ApEn and MSE SampEn) correlated positively with LVEDV (r = 0.19 and 0.20). CONCLUSION: Non linear HRV indices indicated an association between a deteriorated heart rate regulatory system and impaired cardiac function, fluid accumulation and poor physical condition. PMID- 26159751 TI - Current and emerging treatment options for Wiskott-Aldrich syndrome. AB - Wiskott-Aldrich syndrome is a life-threatening primary immunodeficiency associated with a bleeding tendency, eczema and a high incidence of autoimmunity and malignancy. Stem cell transplantation offers the opportunity of cure for all these complications, and over the past 35 years there has been a remarkable improvement in survival following this treatment. Here, we review advances in management of clinical complications pre- and post-transplant, as well as discuss the morbidity Wiskott-Aldrich syndrome patients experience following treatment. For patients with a poorly matched stem cell donor, recent gene therapy trials demonstrate encouraging results and the potential of low-toxicity therapy for all patients. PMID- 26159750 TI - Effects of stem cell transplantation on cognitive decline in animal models of Alzheimer's disease: A systematic review and meta-analysis. AB - Alzheimer's disease (AD), an irreversible progressive neurodegenerative disease, causes characteristic cognitive impairment, and no curative treatments are currently available. Stem cell transplantation offers a powerful tool for the treatment of AD. We conducted a systematic review and meta-analysis of data from controlled studies to study the impact of stem cell biology and experimental design on learning and memory function following stem cell transplantation in animal models of AD. A total of 58 eligible controlled studies were included by searching PubMed, EMBASE, and Web of Science up to April 13, 2015. Meta-analysis showed that stem cell transplantation could promote both learning and memory recovery. Stratified meta-analysis was used to explore the influence of the potential factors on the estimated effect size, and meta-regression analyses were undertaken to explore the sources of heterogeneity for learning and memory function. Publication bias was assessed using funnel plots and Egger's test. The present review reinforces the evidence supporting stem cell transplantation in experimental AD. However, it highlights areas that require well-designed and well reported animal studies. PMID- 26159752 TI - Carbon-doped BN nanosheets for metal-free photoredox catalysis. AB - The generation of sustainable and stable semiconductors for solar energy conversion by photoredox catalysis, for example, light-induced water splitting and carbon dioxide reduction, is a key challenge of modern materials chemistry. Here we present a simple synthesis of a ternary semiconductor, boron carbon nitride, and show that it can catalyse hydrogen or oxygen evolution from water as well as carbon dioxide reduction under visible light illumination. The ternary B C-N alloy features a delocalized two-dimensional electron system with sp(2) carbon incorporated in the h-BN lattice where the bandgap can be adjusted by the amount of incorporated carbon to produce unique functions. Such sustainable photocatalysts made of lightweight elements facilitate the innovative construction of photoredox cascades to utilize solar energy for chemical conversion. PMID- 26159753 TI - Comparative analysis of dietary guidelines in the Spanish-Speaking Caribbean. AB - OBJECTIVE: Dietary guidelines are important education and policy tools to address local nutrition concerns. The current paper presents a comparative analysis of nutrition messages from three Spanish-speaking Caribbean countries (Cuba, Puerto Rico and Dominican Republic) to explore how these dietary guidelines address common public health nutrition concerns, contextualized in different changing food environments and food culture similarities. DESIGN: Qualitative, comparative analysis of current dietary guideline documents and key recommendations. RESULTS: Key recommendations were categorized into sixteen themes (two diet-based, ten food-based and four 'other'). Only the Cuban dietary guidelines included diet based key recommendations. Of the ten food-based key recommendations, only four themes overlapped across the three dietary guidelines (the encouragement of fruits and vegetables, addressing protein sources and fat). Other overlaps were found between dietary guideline pairs, except between Cuba and Puerto Rico. Further analysis revealed differences in levels of specificity and acknowledgement of local dietary patterns and issues, as well as the need to revise the guidelines to account for current scientific advances. CONCLUSIONS: The present study underscored the importance of context in the framing of dietary advice and the influence of national socio-economic and political situations on nutrition policy and education efforts. The results contribute to inform efforts to improve nutrition communication in the region and among migrant communities. PMID- 26159754 TI - Recording of intracranial pressure in conscious rats via telemetry. AB - Although cerebral perfusion pressure (CPP) is known to be fundamental in the control of normal brain function, there have been no previous long-term measurements in animal models. The aim of this study was to explore the stability and viability of long-term recordings of intracranial pressure (ICP) in freely moving rats via a telemetry device. We also developed a repeatable surgical approach with a solid-state pressure sensor at the tip of the catheter placed under the dura and in combination with arterial pressure (AP) measurement to enable the calculation of CPP. Telemeters with dual pressure catheters were implanted in Wistar rats to measure ICP and AP. We found that the signals were stable throughout the 28-day recording period with an average ICP value of 6 +/- 0.8 mmHg. Significant light-dark differences were found in AP (3.1 +/- 2.7 mmHg, P = 0.02) and HR (58 +/- 12 beats/min, P = 0.003), but not ICP (0.3 +/- 0.2 mmHg, P >0.05) or CPP (2.6 +/- 2.8 mmHg, P > 0.05). Use of kaolin to induce hydrocephalus in several rats demonstrates the ability to measure changes in ICP throughout disease progression, validating this new solution for chronic measurement of ICP, CPP, and AP in conscious rats. PMID- 26159755 TI - COX-2 inhibition impairs mechanical stimulation of early tendon healing in rats by reducing the response to microdamage. AB - Early tendon healing can be stimulated by mechanical loading and inhibited by cyclooxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs). Therefore, we investigated if impairment of tendon healing by a COX-2 inhibitor (parecoxib) is related to loading. Because loading might infer microdamage, which also stimulates healing, we also investigated if this effect is inhibited by parecoxib. The Achilles tendon was transected in 114 rats. Three degrees of loading were used: full loading, partial unloading, and unloading (no unloading, Botox injections in the plantar flexor muscles, or Botox in combination with tail suspension). For each loading condition, the rats received either parecoxib or saline. In a second experiment, rats were unloaded with Botox, and the tendon was subjected to microdamage by needling combined with either saline or parecoxib. Mechanical testing day 7 showed that there was a significant interaction between loading and parecoxib for peak force at failure (P < 0.01). However, logarithmic values showed no significant interaction, meaning that we could not exclude that the inhibitory effect of parecoxib was proportionate to the degree of loading. Microbleeding was common in the healing tissue, suggesting that loading caused microdamage. Needling increased peak force at failure (P < 0.01), and this effect of microdamage was almost abolished by parecoxib (P < 0.01). Taken together, this suggests that COX-2 inhibition impairs the positive effects of mechanical loading during tendon healing, mainly by reducing the response to microdamage. PMID- 26159756 TI - Remodeling of left circumflex coronary arterial tree in pacing-induced heart failure. AB - Congestive heart failure (CHF) is a very serious heart disease that manifests an imbalance between left ventricle supply and demand. Although the mechanical demand of the failing heart has been well characterized, the systematic remodeling of the entire coronary arterial tree that constitutes the supply of the myocardium is lacking. We hypothesize that the well-known increase in ventricle wall stress during CHF causes coronary vascular rarefaction to increase the vascular flow resistance, which in turn compromises the perfusion of the heart. Morphometric (diameters, length, and numbers) data of the swine left circumflex (LCx) arterial tree were measured in both CHF (n = 6) and control (n = 6) groups, from which a computer reconstruction of the entire LCx tree was implemented down to the capillary level to enable a hemodynamic analysis of coronary circulation. The vascular flow resistance was increased by ~75% due to a significant decrease of vessel numbers (~45%) and diameters in the first capillary segments (~10%) of the LCx arterial tree after 3-4 wk of pacing. The structural remodeling significantly changed the wall shear stress in vessel segments of the entire LCx arterial tree of CHF animals. This study enhances our knowledge of coronary arterial tree remodeling in heart failure, which provides a deeper understanding of the deterioration of supply-demand relation in left ventricle. PMID- 26159757 TI - The effect of an acute increase in central blood volume on the response of cerebral blood flow to acute hypotension. AB - The purpose of the present study was to examine whether the response of cerebral blood flow to an acute change in perfusion pressure is modified by an acute increase in central blood volume. Nine young, healthy subjects voluntarily participated in this study. To measure dynamic cerebral autoregulation during normocapnic and hypercapnic (5%) conditions, the change in middle cerebral artery mean blood flow velocity was analyzed during acute hypotension caused by two methods: 1) thigh-cuff occlusion release (without change in central blood volume); and 2) during the recovery phase immediately following release of lower body negative pressure (LBNP; -50 mmHg) that initiated an acute increase in central blood volume. In the thigh-cuff occlusion release protocol, as expected, hypercapnia decreased the rate of regulation, as an index of dynamic cerebral autoregulation (0.236 +/- 0.018 and 0.167 +/- 0.025 s(-1), P = 0.024). Compared with the cuff-occlusion release, the acute increase in central blood volume (relative to the LBNP condition) with LBNP release attenuated dynamic cerebral autoregulation (P = 0.009). Therefore, the hypercapnia-induced attenuation of dynamic cerebral autoregulation was not observed in the LBNP release protocol (P = 0.574). These findings suggest that an acute change in systemic blood distribution modifies dynamic cerebral autoregulation during acute hypotension. PMID- 26159758 TI - Inappropriate interpretation of surface EMG signals and muscle fiber characteristics impedes understanding of the control of neuromuscular function. PMID- 26159759 TI - Mechanisms underlying enhancements in muscle force and power output during maximal cycle ergometer exercise induced by chronic beta2-adrenergic stimulation in men. AB - The study was a randomized placebo-controlled trial investigating mechanisms by which chronic beta2-adrenergic stimulation enhances muscle force and power output during maximal cycle ergometer exercise in young men. Eighteen trained men were assigned to an experimental group [oral terbutaline 5 mg/30 kg body weight (bw) twice daily (TER); n = 9] or a control group [placebo (PLA); n = 9] for a 4-wk intervention. No changes were observed with the intervention in PLA. Isometric muscle force of the quadriceps increased (P <= 0.01) by 97 +/- 29 N (means +/- SE) with the intervention in TER compared with PLA. Peak and mean power output during 30 s of maximal cycling increased (P <= 0.01) by 32 +/- 8 and 25 +/- 9 W, respectively, with the intervention in TER compared with PLA. Maximal oxygen consumption (Vo2max) and time to fatigue during incremental cycling did not change with the intervention. Lean body mass increased by 1.95 +/- 0.8 kg (P <= 0.05) with the intervention in TER compared with PLA. Change in single fiber cross-sectional area of myosin heavy chain (MHC) I (1,205 +/- 558 MUm(2); P <= 0.01) and MHC II fibers (1,277 +/- 595 MUm(2); P <= 0.05) of the vastus lateralis muscle was higher for TER than PLA with the intervention, whereas no changes were observed in MHC isoform distribution. Expression of muscle proteins involved in growth, ion handling, lactate production, and clearance increased (P <= 0.05) with the intervention in TER compared with PLA, with no change in oxidative enzymes. Our observations suggest that muscle hypertrophy is the primary mechanism underlying enhancements in muscle force and peak power during maximal cycling induced by chronic beta2-adrenergic stimulation in humans. PMID- 26159760 TI - Using the same cut-off for sulfur hexafluoride and nitrogen multiple-breath washout may not be appropriate. PMID- 26159761 TI - Effects of methionine restriction and endurance exercise on bones of ovariectomized rats: a study of histomorphometry, densitometry, and biomechanical properties. AB - To investigate the effects of dietary methionine restriction (MetR) and endurance exercise on bone quality under a condition of estrogen deficiency, female Sprague Dawley rats (36-wk-old) were assigned to a sham surgery group or one of five ovariectomized groups subjected to interventions of no treatment (Ovx), endurance exercise (Exe), methionine restriction (MetR), methionine restriction plus endurance exercise (MetR + Exe), and estrogen treatment (Est). Rats in the exercise groups were subjected to a treadmill running regimen. MetR and control diets contained 0.172 and 0.86% methionine, respectively. After the 12-wk intervention, all animals were killed, and serum and bone tissues were collected for analyses. Compared with estrogen treatment, MetR diet and endurance exercise showed better or equivalent efficiency in reducing body weight gain caused by ovariectomy (P < 0.05). Whereas only the Est group showed evidence for reduced bone turnover compared with the Ovx group, MetR diet and/or endurance exercise demonstrated efficiencies in downregulating serum insulin, leptin, triglyceride, and thiobarbituric acid reactive substances (P < 0.05). Both the Exe and MetR groups showed higher femoral cortical and total volumetric bone mineral density (vBMD), but only the Exe and Est groups preserved cancellous bone volume and/or vBMD of distal femora (P < 0.05) compared with the Ovx group. After being normalized to body mass, femora of the MetR and MetR + Exe groups had relatively higher bending strength and dimension values followed by the Sham, Exe, and Est groups (P < 0.05). In conclusion, both MetR diet and endurance exercise improved cortical bone properties, but only endurance exercise preserved cancellous bone under estrogen deficiency. PMID- 26159762 TI - Relation between postural sway magnitude and metabolic energy cost during upright standing on a compliant surface. AB - Postural control performance is often described in terms of postural sway magnitude, assuming that lower sway magnitude reflects better performance. However, people do not typically minimize sway magnitude when performing a postural control task. Possibly, other criteria are satisfied when people select the amount of sway they do. Minimal metabolic cost has been suggested as such a criterion. The aim of this study was to experimentally test the relation between sway magnitude and metabolic cost to establish whether metabolic cost could be a potential optimization criterion in postural control. Nineteen healthy subjects engaged in two experiments in which different magnitudes of sway were evoked during upright standing on a foam surface while metabolic energy expenditure, center of pressure (CoP) excursion, and muscle activation were recorded. In one experiment, sway was manipulated by visual feedback of CoP excursion. The other experiment involved verbal instructions of standing still, natural or relaxed. In both experiments, metabolic cost changed with sway magnitude in an asymmetric parabolic fashion, with a minimum around self-selected sway magnitudes and a larger increase at small compared with large sway magnitudes. This metabolic response was paralleled by a change in tonic and phasic EMG activity in the major leg muscles. It is concluded that these results are in line with the notion that metabolic cost can be an optimization criterion used to set postural control and as such could account for the magnitude of naturally occurring postural sway in healthy individuals, although the pathway remains to be elucidated. PMID- 26159763 TI - Effect of short-term exercise-heat acclimation on ventilatory and cerebral blood flow responses to passive heating at rest in humans. AB - Hyperthermia induces hyperventilation and cerebral hypoperfusion in resting humans. We tested the hypothesis that short-term exercise-heat acclimation would alleviate those effects. Twenty healthy male subjects were divided into two groups that performed exercise training in the heat (TR-HEAT, n = 10) or cold (TR COLD, n = 10). Before and after the training, the subjects in both groups participated in passive-heat tests at rest. Training was performed at 37 degrees C (TR-HEAT) or 10 degrees C (TR-COLD) and entailed four 20-min bouts of cycling at 50% peak oxygen uptake separated by 10-min recoveries daily for 6 consecutive days. After TR-HEAT, esophageal temperature was lowered when measured before and during passive heating, as was the esophageal temperature threshold for cutaneous active vasodilation, whereas plasma volume was increased (all P < 0.05). These traditional indices of successful heat acclimation were not all induced by TR COLD (all P > 0.05). TR-HEAT had no significant effect on passive heating-induced increases in minute ventilation, even when evaluated as the esophageal temperature threshold for increases in minute ventilation and the slope relating minute ventilation to esophageal temperature (all P > 0.05). By contrast, TR-HEAT attenuated the passive heating-induced reduction in the cerebral vascular conductance index (middle cerebral artery mean blood velocity/mean arterial pressure) (all P < 0.05). TR-COLD did not attenuate the increase in minute ventilation or the decrease in the cerebral vascular conductance index observed during passive heating (all P > 0.05). These data suggest that in resting heated humans, short-term heat acclimation achieved through moderate-intensity exercise training (i.e., 50% peak oxygen uptake) in the heat does not influence hyperthermia-induced hyperventilation, but it does potentially attenuate cerebral hypoperfusion. PMID- 26159764 TI - An experimental comparison of the relative benefits of work and torque assistance in ankle exoskeletons. AB - Techniques proposed for assisting locomotion with exoskeletons have often included a combination of active work input and passive torque support, but the physiological effects of different assistance techniques remain unclear. We performed an experiment to study the independent effects of net exoskeleton work and average exoskeleton torque on human locomotion. Subjects wore a unilateral ankle exoskeleton and walked on a treadmill at 1.25 m.s(-1) while net exoskeleton work rate was systematically varied from -0.054 to 0.25 J.kg(-1).s(-1), with constant (0.12 N.m.kg(-1)) average exoskeleton torque, and while average exoskeleton torque was systematically varied from approximately zero to 0.18 N.m.kg(-1), with approximately zero net exoskeleton work. We measured metabolic rate, center-of-mass mechanics, joint mechanics, and muscle activity. Both techniques reduced effort-related measures at the assisted ankle, but this form of work input reduced metabolic cost (-17% with maximum net work input) while this form of torque support increased metabolic cost (+13% with maximum average torque). Disparate effects on metabolic rate seem to be due to cascading effects on whole body coordination, particularly related to assisted ankle muscle dynamics and the effects of trailing ankle behavior on leading leg mechanics during double support. It would be difficult to predict these results using simple walking models without muscles or musculoskeletal models that assume fixed kinematics or kinetics. Data from this experiment can be used to improve predictive models of human neuromuscular adaptation and guide the design of assistive devices. PMID- 26159765 TI - Continuous glucose monitoring and hypoglycemia unawareness in type 1 diabetes: a pilot study. AB - BACKGROUND: Looking for strict normoglycemia in type 1 diabetes increases the risk of hypoglycemia, exposing to hypoglycemia unawareness. It has been shown that the early correction of hypoglycemia can help recovering the perception of hypoglycemia. The purpose of this prospective study was to assess the value of sensor-augmented insulin-pump therapy to treat hypoglycemia unawareness. METHODS: Eleven patients with type 1 diabetes and partial or total hypoglycemia unawareness received sensor-augmented insulin-pump therapy combined to the low blood glucose-suspend feature (Paradigm(r) VeoTM pump and Enlite(r) sensors) for three months. RESULTS: Eighty per cent of the patients improved their hypoglycemia unawareness with an increase in the hypoglycemia perception threshold of 31 mg/dL as evaluated by blinded continuous glucose monitoring. These results were correlated to a self-assessment quiz evaluation. Results were sustained at six months (three months after patients stopped using the system). Sensitive neuropathy, untreated hypoglycemia and the area under the curve for hypoglycemia events were associated with less chance of recovery. These devices were globally considered by the patients as simple to use, with no major disadvantages and only a single withdrawal occurred. CONCLUSIONS: Sensor augmented insulin-pump therapy should be considered as a possible treatment of hypoglycemia unawareness. PMID- 26159766 TI - Challenging gender inequity through male involvement in maternal and newborn health: critical assessment of an emerging evidence base. AB - Men's involvement in the health of women and children is considered an important avenue for addressing gender influences on maternal and newborn health. The impact of male involvement around the time of childbirth on maternal and newborn health outcomes was examined as one part of a systematic review of maternal health intervention studies published between 2000 and 2012. Of 33,888 articles screened, 13 eligible studies relating to male involvement were identified. The interventions documented in these studies comprise an emerging evidence base for male involvement in maternal and newborn health. We conducted a secondary qualitative analysis of the 13 studies, reviewing content that had been systematically extracted. A critical assessment of this extracted content finds important gaps in the evidence base, which are likely to limit how 'male involvement' is understood and implemented in maternal and newborn health policy, programmes and research. Collectively, the studies point to the need for an evidence base that includes studies that clearly articulate and document the gender-transformative potential of involving men. This broader evidence base could support the use of male involvement as a strategy to improve both health and gender equity outcomes. PMID- 26159767 TI - Quantitative Glycoproteomic Analysis Identifies Platelet-Induced Increase of Monocyte Adhesion via the Up-Regulation of Very Late Antigen 5. AB - Physiological stimuli, such as thrombin, or pathological stimuli, such as lysophosphatidic acid (LPA), activate platelets circulating in blood. Once activated, platelets bind to monocytes via P-selectin-PSGL-1 interactions but also release the stored contents of their granules. These platelet releasates, in addition to direct platelet binding, activate monocytes and facilitate their recruitment to atherosclerotic sites. Consequently, understanding the changes platelet releasates induce in monocyte membrane proteins is critical. We studied the glyco-proteome changes of THP-1 monocytic cells affected by LPA- or thrombin induced platelet releasates. We employed lectin affinity chromatography combined with filter aided sample preparation to achieve high glyco- and membrane protein and protein sequence coverage. Using stable isotope labeling by amino acids in cell culture, we quantified 1715 proteins, including 852 membrane and 500 glycoproteins, identifying the up-regulation of multiple proteins involved in monocyte extracellular matrix binding and transendothelial migration. Flow cytometry indicated expression changes of integrin alpha5, integrin beta1, PECAM 1, and PSGL-1. The observed increase in monocyte adhesion to fibronectin was determined to be mediated by the up-regulation of very late antigen 5 via a P selectin-PSGL-1 independent mechanism. This novel aspect could be validated on CD14+ human primary monocytes, highlighting the benefits of the improved enrichment method regarding high membrane protein coverage and reliable quantification. PMID- 26159768 TI - Child sex and respiratory sinus arrhythmia reactivity as moderators of the relation between internalizing symptoms and aggression. AB - Previous studies have examined sex differences in physiological responding, including respiratory sinus arrhythmia (RSA) reactivity in response to changing stimulus conditions involving situation specific or gender related cues, in children and adolescents. The present study examined whether RSA reactivity moderates the relation between aggression and internalizing symptoms and whether there are sex differences in this effect. Participants were 82 adolescents (M age = 12.1 years; 44 girls) from the general middle-school population. Peer nominations assessed aggression and internalizing symptoms, and RSA reactivity (defined as change in RSA from baseline to task) was recorded while participants anticipated and responded to an 85 dB signaled white-noise burst. For girls, internalizing symptoms were associated with aggression only if girls showed low RSA reactivity from baseline to task; there was no effect for boys. This association was absent when girls showed high RSA reactivity. Thus, child sex appears to influence not only levels of physiological responding but also relations of physiological responding to comorbidity of adjustment problems. PMID- 26159769 TI - Neurofeedback in three patients in the state of unresponsive wakefulness. AB - Some severely brain injured patients remain unresponsive, only showing reflex movements without any response to command. This syndrome has been named unresponsive wakefulness syndrome (UWS). The objective of the present study was to determine whether UWS patients are able to alter their brain activity using neurofeedback (NFB) technique. A small sample of three patients received a daily session of NFB for 3 weeks. We applied the ratio of theta and beta amplitudes as a feedback variable. Using an automatic threshold function, patients heard their favourite music whenever their theta/beta ratio dropped below the threshold. Changes in awareness were assessed weekly with the JFK Coma Recovery Scale Revised for each treatment week, as well as 3 weeks before and after NFB. Two patients showed a decrease in their theta/beta ratio and theta-amplitudes during this period. The third patient showed no systematic changes in his EEG activity. The results of our study provide the first evidence that NFB can be used in patients in a state of unresponsive wakefulness. PMID- 26159771 TI - [How to promote health competence at work]. AB - Health competence is a key concept in occupational health and safety and workplace health promotion for maintaining and enhancing health resources. The effects of governmental or occupational measures to protect or improve health fall short of what is required with regard to the challenges of a changing workplace, e.g., due to the delimitation of work. To secure employability it is becoming more and more important to encourage the personal responsibility of employees. To offer new conclusions on how employers and employees can promote health competence, a survey is required of the research within the fields of health competence and competence development, and of the status quo in enterprises. In this context, a Delphi Study provides an important contribution, with a focus on small and medium-sized enterprises. The development of an extensive understanding of health competence is essential in a work-related context. Beyond knowledge-based health literacy, an action-oriented concept of competence implies the ability and willingness to act in a reasonable and creative manner in complex situations. The development of health competence requires learning embedded in working processes, which challenges competent behaviour. Enabling informal learning is a promising innovative approach and therefore coordinated operational activities are necessary. Ultimately, this is a matter of suitable organisational measures being implemented to meet the health competence needs of an enterprise. Even though the each individual employee bears his or her own health competence, the development potential lies largely within the prevailing working conditions. PMID- 26159770 TI - Isolation, characterization and antifungal docking studies of wortmannin isolated from Penicillium radicum. AB - During the search for a potent antifungal drug, a cell-permeable metabolite was isolated from a soil isolate taxonomically identified as Penicillium radicum. The strain was found to be a potent antifungal agent. Production conditions of the active compound were optimized and the active compound was isolated, purified, characterized and identified as a phosphoinositide 3-kinase (PI3K) inhibitor, commonly known as wortmannin (Wtmn). This is very first time we are reporting the production of Wtmn from P. radicum. In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re confirmed using various fungal strains. Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho- and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins). We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability. PMID- 26159772 TI - Gold Nanoclusters@Ru(bpy)32+-Layered Double Hydroxide Ultrathin Film as a Cathodic Electrochemiluminescence Resonance Energy Transfer Probe. AB - Herein, it is the first report that a cathodic electrochemiluminescence (ECL) resonance energy transfer (ERET) system is fabricated by layer-by-layer (LBL) electrostatic assembly of CoAl layered double hydroxide (LDH) nanosheets with a mixture of blue BSA-gold nanoclusters (AuNCs) and Ru(bpy)3(2+) (denoted as AuNCs@Ru) on an Au electrode. The possible ECL mechanism indicates that the appearance of CoAl-LDH nanosheets generates a long-range stacking order of the AuNCs@Ru on an Au electrode, facilitating the occurrence of the ERET between BSA AuNC donors and Ru(bpy)3(2+) acceptors on the as-prepared AuNCs@Ru-LDH ultrathin films (UTFs). Furthermore, it is observed that the cathodic ECL intensity can be quenched efficiently in the presence of 6-mercaptopurine (6-MP) in a linear range of 2.5-100 nM with a detection limit of 1.0 nM. On the basis of these interesting phenomena, a facile cathodic ECL sensor has successfully distinguished 6-MP from other thiol-containing compounds (e.g., cysteine and glutathione) in human serum and urine samples. The proposed sensing scheme opens a way for employing the layered UTFs as a platform for the cathodic ECL of Ru(bpy)3(2+). PMID- 26159774 TI - Longitudinal analysis of the developing rhesus monkey brain using magnetic resonance imaging: birth to adulthood. AB - We have longitudinally assessed normative brain growth patterns in naturalistically reared Macaca mulatta monkeys. Postnatal to early adulthood brain development in two cohorts of rhesus monkeys was analyzed using magnetic resonance imaging. Cohort A consisted of 24 rhesus monkeys (12 male, 12 female) and cohort B of 21 monkeys (11 male, 10 female). All subjects were scanned at 1, 4, 8, 13, 26, 39, and 52 weeks; cohort A had additional scans at 156 weeks (3 years) and 260 weeks (5 years). Age-specific segmentation templates were developed for automated volumetric analyses of the T1-weighted magnetic resonance imaging scans. Trajectories of total brain size as well as cerebral and subcortical subdivisions were evaluated over this period. Total brain volume was about 64 % of adult estimates in the 1-week-old monkey. Brain volume of the male subjects was always, on average, larger than the female subjects. While brain volume generally increased between any two imaging time points, there was a transient plateau of brain growth between 26 and 39 weeks in both cohorts of monkeys. The trajectory of enlargement differed across cortical regions with the occipital cortex demonstrating the most idiosyncratic pattern of maturation and the frontal and temporal lobes showing the greatest and most protracted growth. A variety of allometric measurements were also acquired and body weight gain was most closely associated with the rate of brain growth. These findings provide a valuable baseline for the effects of fetal and early postnatal manipulations on the pattern of abnormal brain growth related to neurodevelopmental disorders. PMID- 26159776 TI - Adaptation to NaCl Reduces the Susceptibility of Enterococcus faecalis to Melaleuca alternifolia (Tea Tree) Oil. AB - This study investigated the hypothesis that the salt adaptation response of Enterococcus faecalis alters susceptibility to tea tree oil (TTO). Six E. faecalis isolates were adapted to 6.5 % NaCl, and then exposed to TTO in phosphate-buffered saline (PBS). One isolate was also exposed to TTO in Brain Heart Infusion Broth (BHIB). The viability of salt-adapted and non-adapted control cells was determined at 0, 45 and 90 min and compared. MICs for several antibiotics and TTO were also determined by E test and broth microdilution, respectively. Results showed that susceptibility to TTO in PBS was significantly reduced after salt adaptation for five isolates (83 %) (P < 0.05). Mean differences between salt-adapted and non-adapted cell counts were 2.51 log at 45 min and 2.13 log at 90 min. However, when E. faecalis ATCC 19433 was exposed to TTO in BHIB, no significant differences were seen. In conclusion, salt adaptation resulted in reduced susceptibility to TTO in PBS for the majority of isolates, indicating that cross protection had occurred. This effect was absent in BHIB, suggesting that the uptake of compatible solutes from the growth medium protected non-adapted cells from TTO. Whether this has implications for the clinical effectiveness of TTO remains to be determined. PMID- 26159775 TI - Identification of Paenibacillus as a Symbiont in Acanthamoeba. AB - Amoebae of the genus Acanthamoeba occur worldwide and in addition to being pathogens, are important vehicles for microorganisms with clinical and environmental importance. This study aimed to evaluate the profiling of endosymbionts in 12 isolates of Acanthamoeba using V3 region of 16S rDNA denaturing gradient gel electrophoresis (DGGE) and sequencing. The DGGE enabled us to characterize the endosymbionts diversity in isolates of Acanthamoeba, and to identify Paenibacillus sp., an emerging pathogen, as an amoebic endosymbiont. The results of this study demonstrated that Acanthamoeba is capable of transporting a large number of endosymbionts. This is the first study that reports, the presence of Paenibacillus sp. as amebic symbiont. PMID- 26159777 TI - Risk Assessment for the Spread of Serratia marcescens Within Dental-Unit Waterline Systems Using Vermamoeba vermiformis. AB - Vermamoeba vermiformis is associated with the biofilm ecology of dental-unit waterlines (DUWLs). This study investigated whether V. vermiformis is able to act as a vector for potentially pathogenic bacteria and so aid their dispersal within DUWL systems. Clinical dental water was initially examined for Legionella species by inoculating it onto Legionella selective-medium plates. The molecular identity/profile of the glassy colonies obtained indicated none of these isolates were Legionella species. During this work bacterial colonies were identified as a non-pigmented Serratia marcescens. As the water was from a clinical DUWL which had been treated with AlpronTM, this prompted the question as to whether S. marcescens had developed resistance to the biocide. Exposure to AlpronTM indicated that this dental biocide was effective, under laboratory conditions, against S. marcescens at up to 1 * 10(8) colony forming units/millilitre (cfu/ml). V. vermiformis was cultured for 8 weeks on cells of S. marcescens and Escherichia coli. Subsequent electron microscopy showed that V. vermiformis grew equally well on S. marcescens and E. coli (P = 0.0001). Failure to detect the presence of S. marcescens within the encysted amoebae suggests that V. vermiformis is unlikely to act as a vector supporting the growth of this newly isolated, nosocomial bacterium. PMID- 26159778 TI - Restorative material and loading type influence on the biomechanical behavior of wedge shaped cervical lesions. AB - OBJECTIVES: To evaluate the influence of restorative materials used on the rehabilitation of MOD cavities and loading type, on biomechanical behavior of wedge-shaped (WS) lesions in endodontically treated maxillary premolars. The investigation was conducted by 3D finite element analysis (FEA) and strain gauge test. MATERIALS AND METHODS: Six models were generated, with MOD cavities and endodontic treatment: A (MOD amalgam restoration), R (MOD composite restoration), AL (A + cervical lesion (L)), RL, ALR (A + cervical lesion restored with composite (LR)), and RLR. Each model underwent two compressive loading (100N): axial and oblique-45 degrees angle to the long axis on the buccal cusp. The models were analyzed by von Mises criteria. For strain gauge test, 14 standardized maxillary premolars were treated according to the groups described for FEA. Two strain gauges were bonded on each sample submitted to compressive loading in a mechanical testing machine. RESULTS: A presented higher stress concentration and strain values than R. Oblique loading promoted highest stress concentration and strain rates for all groups. ALR and RLR presented similar stress-strain distribution pattern when compared to A and R. CONCLUSION: The interaction between MOD cavity restored with amalgam and oblique loading propitiated the highest stress concentration and strain values on cervical region and WS lesion. CLINICAL RELEVANCE: The MOD cavity restored with composite resin is a better option than amalgam to improve the biomechanical behavior of wedge shaped lesion, avoiding dental failure. In addition, the occlusal interferences must be removed, allowing homogeneous contact distribution and preventing WS lesion progression. PMID- 26159773 TI - Differential maturation of vesicular glutamate and GABA transporter expression in the mouse auditory forebrain during the first weeks of hearing. AB - Vesicular transporter proteins are an essential component of the presynaptic machinery that regulates neurotransmitter storage and release. They also provide a key point of control for homeostatic signaling pathways that maintain balanced excitation and inhibition following changes in activity levels, including the onset of sensory experience. To advance understanding of their roles in the developing auditory forebrain, we tracked the expression of the vesicular transporters of glutamate (VGluT1, VGluT2) and GABA (VGAT) in primary auditory cortex (A1) and medial geniculate body (MGB) of developing mice (P7, P11, P14, P21, adult) before and after ear canal opening (~P11-P13). RNA sequencing, in situ hybridization, and immunohistochemistry were combined to track changes in transporter expression and document regional patterns of transcript and protein localization. Overall, vesicular transporter expression changed the most between P7 and P21. The expression patterns and maturational trajectories of each marker varied by brain region, cortical layer, and MGB subdivision. VGluT1 expression was highest in A1, moderate in MGB, and increased with age in both regions. VGluT2 mRNA levels were low in A1 at all ages, but high in MGB, where adult levels were reached by P14. VGluT2 immunoreactivity was prominent in both regions. VGluT1 (+) and VGluT2 (+) transcripts were co-expressed in MGB and A1 somata, but co-localization of immunoreactive puncta was not detected. In A1, VGAT mRNA levels were relatively stable from P7 to adult, while immunoreactivity increased steadily. VGAT (+) transcripts were rare in MGB neurons, whereas VGAT immunoreactivity was robust at all ages. Morphological changes in immunoreactive puncta were found in two regions after ear canal opening. In the ventral MGB, a decrease in VGluT2 puncta density was accompanied by an increase in puncta size. In A1, perisomatic VGAT and VGluT1 terminals became prominent around the neuronal somata. Overall, the observed changes in gene and protein expression, regional architecture, and morphology relate to-and to some extent may enable-the emergence of mature sound-evoked activity patterns. In that regard, the findings of this study expand our understanding of the presynaptic mechanisms that regulate critical period formation associated with experience-dependent refinement of sound processing in auditory forebrain circuits. PMID- 26159779 TI - The use of mycophenolate mofetil in experimental encapsulating peritoneal sclerosis. AB - INTRODUCTION: Encapsulated peritoneal sclerosis (EPS) is a rare complication of long-term peritoneal dialysis usually associated with the inadequacy and early termination of dialysis modality. Adequate treatment of peritoneal fibrosis has not been achieved by medical intervention so far. Mycophenolate mofetil (MMF), which inhibits inosine monophosphate dehydrogenase reversibly and highly selectively, is the most widely used drug for maintenance immunosupression in renal transplantation. Recent studies have shown that MMF has also antifibrotic effects. In this study, we evaluated the effects of MMF on EPS model in rats based on antifibrotic effects. MATERIALS AND METHODS: Twenty-four Wistar albino rat have been randomly divided into four groups. Group I (control group) received isotonic saline intraperitoneally (i.p) 2 ml/day for (0-3rd weeks). Group II (chlorhexidine (CG) group) received CG 2 ml/day i.p. for (0-3rd weeks). Group III (chlorhexidine + MMF group) received CG (2 ml/day) i.p. for (0-3rd weeks) plus MMF 30 mg/kg/day peroral (4th-6th weeks). Group IV (resting group) received CG 2 ml/day) i.p. (0-3rd weeks) plus peritoneal resting without any treatment (4th-6th weeks) At the end of the sixth weeks, all of the rats were killed. All of the groups were analyzed in terms of peritoneal thickness, degree of inflammation, vasculopathy, neovascularization and fibrosis. Also, the parietal peritoneal tissue samples were evaluated for matrix metalloproteinase 2 (MMP-2) by using the immunohistochemical analysis. RESULTS: When the CG group was compared with the MMF group, the medication resulted in a statistically significant reduction in peritoneal thickness, inflammation and fibrosis score (53.23 +/- 16.24 vs. 17.22 +/- 3.62, 1 +/- 1.225 vs. 1 +/- 0, 1.6 +/- 0.548 vs. 0.2 +/- 0.447, respectively, all p < 0.05). In the resting group, no beneficial effects on morphological abnormality of the peritoneum were observed as compared with MMF group. However, according to immunohistochemical analysis of the expression of MMP-2 on peritoneal samples, the highest expression of MMP-2 was observed in the MMF group. CONCLUSION: MMF was effective for the treatment of encapsulating peritoneal fibrosis in our rat model. Most recently, MMF may be first choice for EPS due to antifibrotic effect. PMID- 26159780 TI - Are nephrologists involving all physicians for management of sudden cardiac arrest in chronic kidney disease patients? PMID- 26159781 TI - What Motivates Older Adults to Improve Diet and Exercise Patterns? AB - Dietary intake and physical activity are lifestyle behaviors that are learned, developed, and practiced throughout an individual's lifetime. These lifestyle behaviors have a profound role on health and quality of life--with late-life changes still resulting in notable improvements. Despite well documented benefits of behavior change, such changes are extremely challenging. The purpose of this study is to better understand from the perspective of older adults themselves, the factors that may influence their likelihood of making lifestyle changes. Participants were recruited two primary care clinics. 104 older adults ranging in age from 65 to 95 were included. Participants were interviewed about their motivations and plans to change diet and physical activity behaviors following a routine primary care visit. All interviews were transcribed and transcripts were analyzed using a line-by-line coding approach. Older adults reported that their likelihood of making a lifestyle change related to perceptions of old age, personal motivation, and perceived confidence in the ability to make effective changes. These findings suggest the importance of creating more positive images of old age and tailoring health promotion efforts to older adults' motivations and confidence in their ability to make behavior changes. PMID- 26159782 TI - Orofacial manifestations and dental considerations in association with Varadi Papp syndrome: report of a rare case. AB - Varadi-Papp syndrome or oral-facial-digital syndrome type VI (OFDS VI) is a rare, autosomal recessive disorder characterised by a specific congenital malformation of the cerebellum and a broad spectrum of other phenotypic findings. It is distinguished from other OFDSs by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities. Treatment for such patients is often considered challenging due to the presence of intellectual disability, hypotonia, and abnormal respiratory pattern in these patients. The present article reports the oral and systemic manifestations of a 5-year-old female patient having Varadi Papp syndrome, considerations taken in her dental treatment and the successful management performed. The patient was followed up every 3 months for 2 years, to evaluate plaque control and to continue with the plaque control regimen. Periodic oral examinations and maintenance of good oral hygiene helped to improve the quality of life of the child. This case illustrates the favourable treatment outcomes in a Varadi-Papp syndrome patient. Furthermore, the need for periodic oral examinations and maintenance of good oral hygiene to prevent any complications in such patients has been highlighted. PMID- 26159783 TI - MiR-499 Enhances the Cisplatin Sensitivity of Esophageal Carcinoma Cell Lines by Targeting DNA Polymerase beta. AB - BACKGROUND: Human DNA polymerase beta (DNA polymerase beta, polbeta) is a small monomeric protein essential for short-patch base excision repair (BER). It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. METHODS: Luciferase reporter and western blot assays were used to determine whether polbeta is a major target of miR-499. CCK-8, colony-forming survival and in vivo tumor growth assays were conducted to evaluate if miR- 499 can potentially enhance the cisplatin sensitivity and therefore inhibit the proliferation of esophageal cancer (EC) cells. Flow cytometry and immunofluorescence microscopy assays were performed to evaluate whether miR-499 enhance the cisplatin sensitivity and the corresponding apoptosis in EC cells. RESULTS: polbeta was pinpointed as a target gene of miR- 499. Additionally, we identified that miR-499 can enhance cisplatin's function of inhibiting proliferation and of promoting apoptosis in EC9706 and KYSE30 cell lines. CONCLUSIONS: We first investigated whether miR-499 modulates polbeta, and observed the influence of miR-499 up-regulation on the sensitivity of EC cell lines to cisplatin treatment. Our study paves the way for more insightful understanding and application of chemotherapy in esophageal cancer in the future. PMID- 26159785 TI - The first proton sponge-based amino acids: synthesis, acid-base properties and some reactivity. AB - The first hybrid base constructed from 1,8-bis(dimethylamino)naphthalene (proton sponge or DMAN) and glycine, N-methyl-N-(8-dimethylamino-1-naphthyl)aminoacetic acid, was synthesised in high yield and its hydrobromide was structurally characterised and used to determine the acid-base properties via potentiometric titration. It was found that the basic strength of the DMAN-glycine base (pKa = 11.57, H2O) is on the level of amidine amino acids like arginine and creatine and its structure, zwitterionic vs. neutral, based on the spectroscopic (IR, NMR, mass) and theoretical (DFT) approaches has a strong preference to the zwitterionic form. Unlike glycine, the DMAN-glycine zwitterion is N-chiral and is hydrolytically cleaved with the loss of glycolic acid on heating in DMSO. This reaction together with the mild decarboxylative conversion of proton sponge-based amino acids into 2,3-dihydroperimidinium salts under air-oxygen was monitored with the help of the DMAN-alanine amino acid. The newly devised amino acids are unique as they combine fluorescence, strongly basic and redox-active properties. PMID- 26159784 TI - Detecting drug-herbal interaction using a spontaneous reporting system database: an example with benzylpenicillin and qingkailing injection. AB - PURPOSE: The study aims to quantify anaphylaxis signal for combined exposure of benzylpenicilin and qingkailing injection (QI) compared with individual exposure of the two drugs and the background risk based on all other exposures in SRS database. METHODS: Data used in this study were collected during 2003-2014 from China Guangdong Provincial Center of ADR Monitoring. We studied the suspected ADR reports using a case/non-case design. The cases were defined as the reactions coded by WHO-preferred terms of anaphylactic shock or anaphylactoid reaction. Reporting odds ratios (RORs) were used as a measure of disproportionality and were adjusted for age and gender to reduce confounding effects. An observed-to expected ratio Omega was also used for interaction detection. RESULTS: The crude RORs (95 % CIs) for anaphylaxis in patients who used only benzylpenicillin or QI and those who used the two drugs concomitantly compared with patients who used neither of the two drugs were 2.50 (2.34-2.68), 1.59 (1.46-1.73), and 6.22 (3.34 11.58), respectively. The adjusted RORs (95 % CIs) were 2.48 (2.31-2.65), 1.54 (1.41-1.67), and 6.01 (3.22-11.20), respectively, after being adjusted for age and gender. The measured Omega, Omega0, Omega025, and Omega975 was 1.03, 1.09, 0.14, and 1.71, respectively. CONCLUSIONS: Case reports in the database are suggestive of a safety signal which indicates that an interaction between benzylpenicillin and QI resulting in excess risk of anaphylaxis may occur. SRS databases have a potential for signaling unknown drug-herbal interactions. More effort is needed to expand this potential. PMID- 26159786 TI - An Old Flame Never Dies: Survivin in Cancer and Cellular Senescence. AB - Survivin (BIRC5) is highly expressed in the vast majority of human cancers and is associated with chemotherapy resistance, increased tumor recurrence and shortened patient survival, making it an attractive therapeutic target. Initially identified as an inhibitor of apoptosis protein, it also plays a major role in the regulation of cell division. As such, it acts as a subunit of the chromosomal passenger complex, composed of the mitotic kinase aurora B, borealin and inner centromere protein, and is essential for proper chromosome segregation and cytokinesis. For both biological functions, interaction of survivin's nuclear export signal with the nuclear export receptor chromosome region maintenance 1 is absolutely essential. The timely orchestration of survivin's wide protein interaction repertoire is further modulated by different posttranslational modifications occurring in a cell-cycle-dependent manner. Recent data furthermore indicate additional roles of survivin in the DNA damage response, contributing to therapy resistance, yet the underlying molecular details are still not completely resolved. This also holds true for a potential involvement of survivin in senescence regulation. An age-related accumulation of survivin probably contributes to the apoptosis resistance observed in aged as well as in senescent cells, while it might promote escape from therapy-induced senescence. This review seeks to integrate the current knowledge on survivin's diverse and complex biological functions. By linking the 'old' facts about survivin with recent findings in research areas such as DNA damage response and aging, we want to highlight survivin's crucial role in a variety of cellular processes. PMID- 26159787 TI - What does "integrative medicine" provide to daily scientific clinical care? AB - Integrative medicine is an ambitious and noble-minded attempt to address the shortcomings of the current public health systems in our Western societies, which is restricted by the limited time available, especially in outpatient clinics. Integrative medicine also does not limit the possibilities of useful therapies that have been tested over the centuries (from China, India, etc.) or of certain resources that do not achieve the level of desired scientific credibility but that present certain therapeutic support in specific cases (homeopathy, acupuncture, etc.) but still require a scientific approach. Finally, the resource of botanical products (phytotherapy) constitutes a wide range of possibilities that universities can (and do) make progress on by providing drug brands for these products through the use of the scientific method and evidence-based medical criteria. This approach will help avoid the irrationality of the daily struggle between conventional scientific medicine (which we apply to the immense majority of patients) and the other diagnostic-therapeutic "guidelines" (natural medicine, alternative medicine, complementary medicine, patient-focused medicine and others). PMID- 26159788 TI - Molecular and biochemical characterization of the UDP-glucose: Anthocyanin 5-O glucosyltransferase from Vitis amurensis. AB - Generally, red Vitis vinifera grapes only contain monoglucosidic anthocyanins, whereas most non-vinifera red grapes of the Vitis genus have both monoglucosidic and bis-glucosidic anthocyanins, the latter of which are believed to be more hydrophilic and more stable. Although previous studies have established the biosynthetic mechanism for formation of monoglucosidic anthocyanins, less attention has been paid to that of bis-glucosidic anthocyanins. In the present research, the full-length cDNA of UDP-glucose: anthocyanin 5-O glucosyltransferase from Vitis amurensis Rupr. cv. 'Zuoshanyi' grape (Va5GT) was cloned. After acquisition and purification of recombinant Va5GT, its enzymatic parameters were systematically analyzed in vitro. Recombinant Va5GT used malvidin 3-O-glucoside as its optimum glycosidic acceptor when UDP-glucose was used as the glycosidic donor. Va5GT-GFP was found to be located in the cytoplasm by analyzing its subcellular localization with a laser-scanning confocal fluorescence microscope, and this result was coincident with its metabolic function of modifying anthocyanins in grape cells. Furthermore, the relationship between the transcriptional expression of Va5GT and the accumulation of anthocyanidin bis glucosides during berry development suggested that Va5GT is a key enzyme in the biosynthesis of bis-glucosidic anthocyanins in V. amurensis grape berries. PMID- 26159789 TI - Resveratrol Preconditioning Induces a Novel Extended Window of Ischemic Tolerance in the Mouse Brain. AB - BACKGROUND AND PURPOSE: Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered 2 days before global ischemia in rats. This protection is linked to silent information regulator 2 homologue 1 (Sirt1) and enhanced mitochondrial function possibly through its repression of uncoupling protein 2. Brain-derived neurotrophic factor (BDNF) is another neuroprotective protein associated with Sirt1. In this study, we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice. METHODS: We tested 4 different RPC paradigms against a middle cerebral artery occlusion model of stroke. Infarct volume and neurological score were calculated 24 hours after middle cerebral artery occlusion. Sirt1-chromatin binding was evaluated by ChIP qPCR. Percoll gradients were used to isolate synaptic fractions, and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay. RESULTS: Although repetitive RPC induced neuroprotection from middle cerebral artery occlusion, strikingly one application of RPC 14 days before middle cerebral artery occlusion showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days after RPC, Sirt1 protein was increased 1.5-fold and differentially bound to the uncoupling protein 2 and BDNF promoter regions. Accordingly, synaptic uncoupling protein 2 level decreased by 23% and cortical BDNF concentration increased 26%. CONCLUSIONS: RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days. Our data suggest that this tolerance may be mediated by Sirt1 through upregulation of BDNF and downregulation of uncoupling protein 2. PMID- 26159790 TI - Predictors of Mortality in Acute Ischemic Stroke Intervention: Analysis of the North American Solitaire Acute Stroke Registry. AB - BACKGROUND AND PURPOSE: Failure to recanalize predicts mortality in acute ischemic stroke. In the North American Solitaire Acute Stroke registry, we investigated parameters associated with mortality in successfully recanalized patients. METHODS: Logistic regression was used to evaluate baseline characteristics and recanalization parameters for association with 90-day mortality. A multivariable model was developed based on backward selection with retention criteria of P<0.05 from factors with at least marginal significance (P<=0.10), then refit to minimize the number of excluded cases (missing data). RESULTS: Successfully recanalized patients had lower mortality (25.2% [59/234] versus 46.9% [38/81] P<0.001). There was no difference in symptomatic intracranial hemorrhage between patients with successful versus failed recanalization (9% [21/234] versus 14% [11/79]; P=0.205). However, mortality was significantly higher in patients with symptomatic intracranial hemorrhage (72% [23/32] versus 26% [73/281]; P<0.001). Proximal occlusion (internal carotid artery or vertebrobasilar), initial National Institutes of Health Stroke Scale>=18, use of rescue therapy (P<0.05), and 3+ passes (P<0.10) were associated with mortality in recanalized patients. In the multivariate model with good predictive power (c index=0.72), proximal occlusion, initial National Institutes of Health Stroke Scale>=18, and use of rescue therapy remained significant independent predictors of 90-day mortality. CONCLUSIONS: Failure to recanalize and presence of symptomatic intracranial hemorrhage resulted in increased mortality. Despite successful recanalization, proximal occlusion, high National Institutes of Health Stroke Scale, and need for rescue therapy were predictors of mortality. PMID- 26159791 TI - Computed Tomography Perfusion in Acute Ischemic Stroke: Is It Ready for Prime Time? PMID- 26159792 TI - Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke. AB - BACKGROUND AND PURPOSE: It is unknown whether women and men with acute ischemic stroke respond similar to an antioxidant regimen administered in combination with thrombolysis. Here, we investigated the independent effect of sex on the response to uric acid (UA) therapy in patients with acute stroke treated with alteplase. METHODS: In the Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke (URICO-ICTUS) trial, 206 women and 205 men were randomized to UA 1000 mg or placebo. In this reanalysis of the trial, the primary outcome was the rate of excellent outcome at 90 days (modified Rankin Scale, 0-1, or 2, if premorbid score of 2) in women and men using regression models adjusted for confounders associated with sex. The interaction of UA levels by treatment on infarct growth was assessed in selected patients. RESULTS: Excellent outcome occurred in 47 of 111 (42%) women treated with UA, and 28 of 95 (29%) treated with placebo, and in 36 of 100 (36%) men treated with UA and 38 of 105 (34%) treated with placebo. Treatment and sex interacted significantly with excellent outcome (P=0.045). Thus, UA therapy doubled the effect of placebo to attain an excellent outcome in women (odd ratio [95% confidence interval], 2.088 [1.050 4.150]; P=0.036), but not in men (odd ratio [95% confidence interval], 0.999 [0.516-1.934]; P=0.997). The interactions between treatment and serum UA levels (P<0.001) or allantoin/UA ratio (P<0.001) on infarct growth were significant only in women. CONCLUSIONS: In women with acute ischemic stroke treated with alteplase, the administration of UA reduced infarct growth in selected patients and was better than placebo to reach excellent outcome. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00860366. PMID- 26159793 TI - Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke. AB - BACKGROUND AND PURPOSE: Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. METHODS: Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N~2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. RESULTS: One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7*10( 04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8*10(-04)) and the cardioembolic subtype (smallest P=1.7*10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). CONCLUSIONS: Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. PMID- 26159794 TI - Antithrombotic Treatment Following Intracerebral Hemorrhage in Patients With and Without Atrial Fibrillation. AB - BACKGROUND AND PURPOSE: Patients who survive intracerebral hemorrhage (ICH) often have compelling indications for anticoagulant and antiplatelet medication. This nationwide observational study aimed to determine the extent and predictors of antithrombotic treatment after ICH in Sweden. METHODS: Patients with a first-ever ICH in the Swedish Stroke Register (Riksstroke) 2005 to 2012 who survived hospital discharge were included. Riksstroke data were individually linked with other national registers to determine comorbid conditions and dispensed prescriptions of antithrombotic agents. RESULTS: Among the 2777 patients with atrial fibrillation (AF), the proportion with a dispensed prescription of antithrombotic agents was 8.5% (anticoagulants) and 36.6% (antiplatelet agents) within 6 months and 11.1% (anticoagulants) and 43.6% (antiplatelet agents) within 1 year. Among the 11 268 patients without AF, the corresponding figures were 1.6% (anticoagulants) and 13.8% (antiplatelet agents) within 6 months and 2.0% (anticoagulants) and 17.5% (antiplatelet agents) within 1 year. In patients with AF, predictors of anticoagulant treatment were less severe ICH, younger age, previous anticoagulation, valvular disease, and previous ischemic stroke. High CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke [doubled], vascular disease, age, and sex category [female]) scores did not correlate with anticoagulant treatment. There was a positive correlation between high CHA2DS2-VASc and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol) scores (rs=0.590, P<0.001). CONCLUSIONS: In majority of patients who receive antithrombotic agents, treatment is initiated within 6 months of ICH. Still, many patients with compelling indications for antithrombotic treatment are not prescribed antithrombotic agents. Factors other than high risk of embolic stroke by CHA2DS2-VASc in ICH survivors with concurrent AF are used to guide the anticoagulant treatment decision in Swedish clinical practice. PMID- 26159795 TI - Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis. AB - BACKGROUND AND PURPOSE: Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. METHODS: Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan-Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox regression to investigate whether stroke type was outcome predictor. RESULTS: 2731 patients were followed-up for a mean of 30.5+/-24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%-72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%-42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%-35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%-31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52-0.94]). CONCLUSIONS: Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes. PMID- 26159796 TI - Estimating Total Cerebral Microinfarct Burden From Diffusion-Weighted Imaging. AB - BACKGROUND AND PURPOSE: Cerebral microinfarcts (CMI) are important contributors to vascular cognitive impairment. Magnetic resonance imaging diffusion-weighted imaging (DWI) hyperintensities have been suggested to represent acute CMI. We aim to describe a mathematical method for estimating total number of CMI based on the presence of incidental DWI lesions. METHODS: We reviewed magnetic resonance imaging scans of subjects with cognitive decline, cognitively normal subjects and previously reported subjects with past intracerebral hemorrhage (ICH). Based on temporal and spatial characteristics of DWI lesions, we estimated the annual rate of CMI needed to explain the observed rate of DWI lesion detection in each group. To confirm our estimates, we performed extensive sampling for CMI in the brain of a deceased subject with past lobar ICH who found to have a DWI lesion during life. RESULTS: Clinically silent DWI lesions were present in 13 of 343 (3.8%) cognitively impaired and 10 of 199 (5%) cognitively intact normal non-ICH patients, both lower than the incidence in the past ICH patients (23 of 178; 12.9%; P<0.0006). The predicted annual incidence of CMI ranges from 16 to 1566 for non-ICH and 50 to 5041 for ICH individuals. Histological sampling revealed a total of 60 lesions in 32 sections. Based on previously reported methods, this density of CMI yields an estimated total brain burden maximum likelihood estimate of 9321 CMIs (95% confidence interval, 7255-11 990). CONCLUSIONS: Detecting even a single DWI lesion suggests an annual incidence of hundreds of new CMI. The cumulative effects of these lesions may directly contribute to small-vessel related vascular cognitive impairment. PMID- 26159797 TI - Rickettsial infections in ticks from reptiles, birds and humans in Honduras. AB - Ticks were collected from captive reptiles, wild birds, and incidentally from humans at two locations in Honduras and part of these were tested for the presence of Rickettsia using polymerase chain reaction. The following species of ticks were found: Amblyomma dissimile on Iguanidae reptiles, Amblyomma longirostre and Amblyomma nodosum on birds, and Amblyomma mixtum (Amblyomma cajennense complex) on humans. A. dissimile was infected with Rickettsia sp. strain Colombianensi. Both A. longirostre and A. mixtum were infected with Candidatus 'Rickettsia amblyommii'. This study provides the first report of rickettsial infections in ticks from reptiles, birds and humans in Honduras. New host - Amblyomma tick associations are documented. PMID- 26159798 TI - Patterns of tick infestation and their Borrelia burgdorferi s.l. infection in wild birds in Portugal. AB - Wild birds may act as reservoirs for zoonotic pathogens and may be mechanical carriers of pathogen infected vector ticks through long distances during migration. The aim of this study was to assess tick infestation patterns in birds in Portugal and the prevalence of tick infection by Borrelia burgdorferi s.l. using PCR techniques. Seven tick species were collected from birds including Haemaphysalis punctata, Hyalomma spp., Ixodes acuminatus, Ixodes arboricola, Ixodes frontalis, Ixodes ricinus and Ixodes ventalloi. We found that I. frontalis and Hyalomma spp. were the most common ticks infesting birds of several species and that they were widespread in Portugal. Turdus merula was the bird species that presented the highest diversity of infesting ticks and had one of the highest infestation intensities. B. burgdorferi s.l. was detected in 7.3% (37/505) of Ixodidae ticks derived from birds. The most common genospecies was Borrelia turdi (6.9%), detected in ticks collected from Parus major, T. merula and Turdus philomelos, but Borrelia valaisiana (0.2%) and one Borrelia sp. (0.2%) similar to Borrelia bissettii (96% of similarity of the flaB gene in Blastn) were also detected. This study contributed to a better knowledge of the Ixodidae tick fauna parasitizing birds in Western Europe and to the assessment of the prevalence of B. burgdorferi s.l. associated with birds and their ticks. PMID- 26159799 TI - Flip-angle profile of slice-selective excitation and the measurement of the MR longitudinal relaxation time with steady-state magnetization. AB - In MRI, the flip angle (FA) of slice-selective excitation is not uniform across the slice-thickness dimension. This work investigates the effect of the non uniform FA profile on the accuracy of a commonly-used method for the measurement, in which the T1 value, i.e., the longitudinal relaxation time, is determined from the steady-state signals of an equally-spaced RF pulse train. By using the numerical solutions of the Bloch equation, it is shown that, because of the non uniform FA profile, the outcome of the T1 measurement depends significantly on T1 of the specimen and on the FA and the inter-pulse spacing tau of the pulse train. A new method to restore the accuracy of the T1 measurement is described. Different from the existing approaches, the new method also removes the FA profile effect for the measurement of the FA, which is normally a part of the T1 measurement. In addition, the new method does not involve theoretical modeling, approximation, or modification to the underlying principle of the T1 measurement. An imaging experiment is performed, which shows that the new method can remove the FA-, the tau-, and the T1-dependence and produce T1 measurements in excellent agreement with the ones obtained from a gold standard method (the inversion recovery method). PMID- 26159800 TI - Clinical Features of Patients Treated with Endoscopic Sinus Surgery for Posttraumatic Paranasal Sinus Mucocele. AB - AIM: The purpose of this study was to analyze the clinical features of patients with posttraumatic paranasal sinus mucocele (PSM). SUBJECTS AND METHODS: Between 2009 and 2013, we performed endoscopic sinus surgery (ESS) on 68 patients with PSM at the Department of Otolaryngology - Head and Neck Surgery at Hyogo College of Medicine. Five male patients (age range, 45-76 years) with posttraumatic PSM were analyzed retrospectively. Diagnosis was based on the history of injury and radiological findings. RESULTS: Posttraumatic PSM was found in 7% (5/68) of patients. The mean interval from injury to diagnosis was 28.4 years. All patients had frontal sinus mucocele. Four patients had symptoms of headache, diplopia, visual field defect, and forehead swelling, and 1 patient was asymptomatic. ESS was performed under general anesthesia in all cases, and the symptoms improved postoperatively. Reoperation was required in 1 patient (20%) because headache developed with obstruction of the frontal drainage route 7 months after ESS. CONCLUSIONS: Posttraumatic PSM was the least frequent form of PSM and was located predominantly in the frontal sinus, causing symptoms long after the forehead injury. The important lessons to be learned for treating posttraumatic PSM are to obtain a detailed history and to enlarge the route to the cyst to avoid its recurrence. PMID- 26159801 TI - Marine biodegradation of crude oil in temperate and Arctic water samples. AB - Despite increased interest in marine oil exploration in the Arctic, little is known about the fate of Arctic offshore oil pollution. Therefore, in the present study, we examine the oil degradation potential for an Arctic site (Disko Bay, Greenland) and discuss this in relation to a temperate site (North Sea, Denmark). Biodegradation was assessed following exposure to Oseberg Blend crude oil (100 mg L(-1)) in microcosms. Changes in oil hydrocarbon fingerprints of polycyclic aromatic hydrocarbons (PAHs), alkyl-substituted PAHs, dibenzothiophenes, n alkanes and alkyltoluenes were measured by gas chromatography-mass spectrometry (GC-MS). In the Disko Bay sample, the degradation order was n alkanes>alkyltoluenes (para->meta->ortho-isomers)>PAHs and dibenzothiophenes, whereas, the degradation order in the North Sea samples was PAHs and dibenzothiophenes>alkyltoluenes>n-alkanes. These differences in degradation patterns significantly affect the environmental risk of oil spills and emphasise the need to consider the specific environmental conditions when conducting risk assessments of Arctic oil pollution. PMID- 26159802 TI - Correction of static axial alignment in children with knee varus or valgus deformities through guided growth: Does it also correct dynamic frontal plane moments during walking? AB - Malaligned knees are predisposed to the development and progression of unicompartmental degenerations because of the excessive load placed on one side of the knee. Therefore, guided growth in skeletally immature patients is recommended. Indication for correction of varus/valgus deformities are based on static weight bearing radiographs. However, the dynamic knee abduction moment during walking showed only a weak correlation to malalignment determined by static radiographs. Therefore, the aim of the study was to measure the effects of guided growth on the normalization of frontal plane knee joint moments during walking. 15 legs of 8 patients (11-15 years) with idiopathic axial varus or valgus malalignment were analyzed. 16 typically developed peers served as controls. Instrumented gait analysis and clinical assessment were performed the day before implantation and explantation of eight-plates. Correlation between static mechanical tibiofemoral axis angle (MAA) and dynamic frontal plane knee joint moments and their change by guided growth were performed. The changes in dynamic knee moment in the frontal plane following guided growth showed high and significant correlation to the changes in static MAA (R=0.97, p<0.001). Contrary to the correlation of the changes, there was no correlation between static and dynamic measures in both sessions. In consequence two patients that had a natural knee moment before treatment showed a more pathological one after treatment. In conclusion, the changes in the dynamic load situation during walking can be predicted from the changes in static alignment. If pre-surgical gait analysis reveals a natural load situation, despite a static varus or valgus deformity, the intervention must be critically discussed. PMID- 26159803 TI - Immunoglobulins in Neonates with Rhesus Hemolytic Disease of the Fetus and Newborn: Long-Term Outcome in a Randomized Trial. AB - OBJECTIVE: Prophylactic intravenous immunoglobulin (IVIg) does neither reduce the need for exchange transfusion nor the rates of other adverse neonatal outcomes in neonates with rhesus hemolytic disease of the fetus and newborn (rhesus HDFN) according to our randomized controlled trial analysis. Our objective was to assess the long-term neurodevelopmental outcome in the children included in the trial and treated with either IVIg or placebo. METHODS: All families of the children included in the trial were asked to participate in this follow-up study. The long-term neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests. The primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe cognitive and/or motor developmental delay (with a test score of less than -2 SD), bilateral deafness or blindness. RESULTS: Sixty-six of the 80 children (82.5%) who had been recruited to the initial randomized controlled trial participated in the follow-up study. The children were assessed at a median age of 4 years (range 2-7). The median cognitive score was 96 (range 68-118) in the IVIg group and 97 (range 66-118) in the placebo group (p = 0.79). There was no difference in the rate of neurodevelopmental impairment between the IVIg and the placebo group [3% (1/34) vs. 3% (1/32); p = 1.00]. CONCLUSIONS: The long-term neurodevelopmental outcome in children treated with IVIg was not different from that in children treated with placebo. Standardized long-term follow-up studies with large enough case series and sufficient power are needed to replicate these findings. PMID- 26159804 TI - Temporal Expression of miRNAs in Laser Capture Microdissected Palate Medial Edge Epithelium from Tgfbeta3(-/-) Mouse Fetuses. AB - Clefting of the secondary palate is the most common birth defect in humans. Midline fusion of the bilateral palatal processes is thought to involve apoptosis, epithelial to mesenchymal transition, and cell migration of the medial edge epithelium (MEE), the specialized cells of the palate that mediate fusion of the palatal processes during fetal development. Data presented in this manuscript are the result of analyses designed to identify microRNAs that are expressed and regulated by TGFbeta3 in developing palatal MEE. The expression of 7 microRNAs was downregulated and 1 upregulated in isolated MEE from wildtype murine fetuses on gestational day (GD) 13.5 to GD14.5 (prior to and during epithelial fusion of the palatal processes, respectively). Among this group were miRNAs linked to apoptosis (miR-378) and epithelial to mesenchymal transformation (miR-200b, miR 205, and miR-93). Tgfbeta3(-/-) fetuses, which present with a complete and isolated cleft of the secondary palate, exhibited marked dysregulation of distinct miRNAs both in the palatal MEE and mesenchyme when compared to comparable wild-type tissue. These included, among others, miRNAs known to affect apoptosis (miR-206 and miR-186). Dysregulation of miRNAs in the mesenchyme underlying the palatal MEE of Tgfbeta3(-/-) fetuses is also discussed in relation to epithelial-mesenchymal transformation of the MEE. These results are the first systematic analysis of the expression of microRNAs in isolated fetal palatal epithelium and mesenchyme. Moreover, analysis of the Tgfbeta3 knockout mouse model has enabled identification of miRNAs with altered expression that may contribute to the cleft palate phenotype. PMID- 26159805 TI - Leukoplakia, Oral Cavity Cancer Risk, and Cancer Survival in the U.S. Elderly. AB - Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and the benefits of leukoplakia screening for improving OCC outcomes are currently unclear. We conducted a case-cohort study of U.S. adults ages >=65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage. We identified leukoplakia diagnoses through Medicare claims, and OCC diagnoses through SEER cancer registries. Weighted Cox regression was used to estimate leukoplakia associations with OCC incidence, and the absolute OCC risk following leukoplakia diagnosis was calculated. Among OCC cases, we compared OCC stage and OCC survival between cases with a prior leukoplakia diagnosis versus those without prior leukoplakia. Among 470,266 individuals in the SEER-Medicare subcohort, 1,526 (0.3%) had a leukoplakia diagnosis. Among people with leukoplakia, the cumulative OCC incidence was 0.7% at 3 months and 2.5% at 5 years. OCC risk was most increased <3 months after leukoplakia diagnosis (HR, 115), likely representing the diagnosis of prevalent cancers. Nonetheless, risk remained substantially increased in subsequent follow-up [HR >= 3 months, 24; 95% confidence interval (CI), 22-27; HR >= 12 months, 22, 95% CI, 20-25]. Among OCC cases (N = 8,927), those with prior leukoplakia were less likely to be diagnosed at regional/distant stage (OR, 0.36; 95% CI, 0.30-0.43), and had lower mortality (HR, 0.74; 95% CI, 0.65-0.84) when compared with OCC cases without a prior leukoplakia. Individuals with leukoplakia have substantially elevated risk of OCC. Lower stage and better survival after OCC diagnosis suggest that leukoplakia identification can lead to earlier OCC detection and reduced mortality. PMID- 26159806 TI - Advancing the field of health systems research synthesis. AB - Those planning, managing and working in health systems worldwide routinely need to make decisions regarding strategies to improve health care and promote equity. Systematic reviews of different kinds can be of great help to these decision makers, providing actionable evidence at every step in the decision-making process. Although there is growing recognition of the importance of systematic reviews to inform both policy decisions and produce guidance for health systems, a number of important methodological and evidence uptake challenges remain and better coordination of existing initiatives is needed. The Alliance for Health Policy and Systems Research, housed within the World Health Organization, convened an Advisory Group on Health Systems Research (HSR) Synthesis to bring together different stakeholders interested in HSR synthesis and its use in decision-making processes. We describe the rationale of the Advisory Group and the six areas of its work and reflects on its role in advancing the field of HSR synthesis. We argue in favour of greater cross-institutional collaborations, as well as capacity strengthening in low- and middle-income countries, to advance the science and practice of health systems research synthesis. We advocate for the integration of quasi-experimental study designs in reviews of effectiveness of health systems intervention and reforms. The Advisory Group also recommends adopting priority-setting approaches for HSR synthesis and increasing the use of findings from systematic reviews in health policy and decision-making. PMID- 26159808 TI - Associations between narcissism and emotion regulation difficulties: Respiratory sinus arrhythmia reactivity as a moderator. AB - The aim of the current study was to examine the direct and interactive effects of two types of narcissism (overt and covert) and respiratory sinus arrhythmia (RSA) reactivity on emotion regulation difficulties in 227 undergraduate students. Overt and covert narcissism and emotion regulation difficulties were assessed with self-report measures (narcissistic personality inventory (NPI)-16, hypersensitive narcissism scale (HSNS), and difficulties in emotion regulation scale (DERS)), and physiological data were measured during the baseline, stress (a public-speaking task), and recovery periods in the laboratory. Results indicated that overt narcissism was negatively related to a lack of emotional awareness and emotional clarity, whereas covert narcissism was positively related to overall emotion regulation difficulties, nonacceptance of emotional responses, impulse control difficulties, limited access to emotion regulation strategies, and a lack of emotional clarity. RSA reactivity in response to a mock job interview moderated the associations between covert narcissism (as a predictor) and overall emotion regulation difficulties and impulse control difficulties (as outcomes). This finding showed that a greater stress-induced RSA decrease may serve as a protective factor and ameliorate the effect of covert narcissism on individuals' emotion regulation difficulties. PMID- 26159809 TI - Mismatch responses and deviance detection in N-methyl-D-aspartate (NMDA) receptor hypofunction and developmental models of schizophrenia. AB - Reductions in the size of the mismatch negativity (MMN), an event-related potential component elicited in response to unexpected stimuli, are arguably the most robust neurophysiological findings in schizophrenia. Several studies have now demonstrated that 'true' human-like deviance detection mismatch responses (MMRs) can be generated in the rodent brain and therefore that animal models can be used to examine the neurobiology of schizophrenia-like MMR impairments and investigate the efficacy of new treatments in addressing underlying neurobiological mechanisms. Two broad categories of animal models have been examined for schizophrenia-like MMRs: models involving N-methyl-D-aspartate receptor hypofunction, and models involving an insult or exposure during development. While these models have been shown to exhibit reductions in MMRs, it is still unclear whether or not these reductions involve changes to neural adaptation to repetitive stimuli or whether they reflect impairments in the response to unexpected deviations in regular patterns. PMID- 26159807 TI - Tsc1 is a Critical Regulator of Macrophage Survival and Function. AB - BACKGROUND/AIMS: Tuberous sclerosis complex 1 (Tsc1) has been shown to regulate M1/M2 polarization of macrophages, but the precise roles of Tsc1 in the function and stability of macrophages are not fully understood. Here we show that Tsc1 is required for regulating the survival, migration and phagocytosis of macrophages. METHODS: Mice with Tsc1 homozygous deletion in myeloid cells (LysMCreTsc1(flox/flox); Tsc1 KO) were obtained by crossing Tsc1(flox/flox) mice with mice expressing Cre recombinase under the control of Lysozyme promoter (LysMCre). The apoptosis and growth of macrophages were determined by flow cytometry and Real-time PCR (RT-PCR). The phagocytosis was determined using a VybrantTM phagocytosis assay kit. The migration of macrophages was determined using transwell migration assay. RESULTS: Peritoneal macrophages of Tsc1 KO mice exhibited increased apoptosis and enlarged cell size. Both M1 and M2 phenotypes in Tsc1-deficient macrophages were elevated in steady-state as well as in inflammatory conditions. Tsc1-deficient macrophages demonstrated impaired migration and reduced expression of chemokine receptors including CCR2 and CCR5. Phagocytosis activity and ROS production were enhanced in Tsc1-deficient macrophages. Furthermore, pharmacological inhibition of the mammalian target of rapamycin complex 1 (mTORC1) partially reversed the aberrance of Tsc1-deficient macrophages. CONCLUSION: Tsc1 plays a critical role in regulating macrophage survival, function and polarization via inhibition of mTORC1 activity. PMID- 26159810 TI - Stimulus-specific adaptation in the inferior colliculus: The role of excitatory, inhibitory and modulatory inputs. AB - Patients suffering from pathologies such as schizophrenia, depression or dementia exhibit cognitive impairments, some of which can be reflected in event-related potential (ERP) measurements as the mismatch negativity (MMN). The MMN is one of the most commonly used ERPs and provides an electrophysiological index of auditory change or deviance detection. Moreover, MMN has been positioned as a potentially promising biomarker candidate for the diagnosis and prediction of the outcome of schizophrenia. Dysfunction of neural receptors has been linked to the etiopathology of schizophrenia or the induction of psychophysiological anomalies similar to those observed in schizophrenia. Stimulus-specific adaptation (SSA) is a neural mechanism that contributes to the upstream processing of auditory change detection. Auditory neurons that exhibit SSA specifically adapt their response to repetitive sounds but maintain their excitability to respond to rare ones. Thus, by studying the role of neuronal receptors on SSA, we can contribute to detangle the cellular bases of the impairments in deviance processing occurring in mental pathologies. Here, we review the current knowledge on the effect of GABAA mediated inhibition and the modulation of acetylcholine on SSA in the inferior colliculus, and we add unpublished original data obtained blocking glutamate receptors. We found that the blockade of GABAA and glutamate receptors mediates an overall increase or decrease of the neural response, respectively, while acetylcholine affects only the response to the repetitive sounds. These results demonstrate that GABAergic, glutamatergic and cholinergic receptors play different and complementary roles on shaping SSA. PMID- 26159811 TI - Theoretical study of the effect of shear deformable shell model, elastic foundation and size dependency on the vibration of protein microtubule. AB - In this paper, isotropic cylindrical shell model with first order shear deformation theory based on modified couple stress theory is used to investigate the mechanical behavior of microtubules and to consider the size effect in the nano-scale. Besides, partial equations of shell motion with classical and non classical corresponding boundary conditions are derived from Hamilton's principle. The study models the microtubule as a simply supported shell and the Navier procedure is used to solve the vibration problem. To simulate the environment of microtubule, Pasternak foundation is used. The free vibration of the microtubule is examined in the presence and absence of cytoplasm, and the significant parameter, length dependence flexural rigidity is determined based on the new model. Finally, the effect of different system parameters such as length, size effect parameters, shear modulus ratio and substrate parameters on free vibration microtubule is investigated. Comparison of the results of the new model with the classical model and the results obtained by other researchers reveals that the model presented in this paper is more accurate than other models used in this area and in better agreement with experimental data. PMID- 26159812 TI - Microtubule patterning in the presence of moving motor proteins. AB - Cytoskeletal polymers such as microtubules (MTs) interact with motor proteins to form higher-order structures. In vitro experiments have shown that MT patterns such as asters, bundles, and vortices can form under the influence of a single type of dynamic motor protein. MTs also can form anti-parallel bundles, similar to bundles that form the mitotic spindle during cell division, under the influence of two types of moving motors with opposite directionality. Despite the importance of MT structures, their mechanism of formation is not yet understood. We develop an integro-partial differential equation model to describe the dynamic interactions between MTs and moving motor proteins. Our model takes into account motor protein speed, processivity, density, and directionality, as well as MT treadmilling and reorganization due to interactions with motors. Simulation results show that plus-end directed motor proteins can form vortex patterns at low motor density, while minus-end directed motor proteins form aster patterns at similar densities. Also, motor proteins with opposite directionality are able to organize MTs into anti-parallel bundles. Our model is able to provide a quantitative and qualitative description of MT patterning, providing insights into possible mechanisms of spindle formation. PMID- 26159813 TI - Configuration coordinate energy level diagrams of intervalence and metal-to-metal charge transfer states of dopant pairs in solids. AB - Configuration coordinate diagrams, which are normally used in a qualitative manner for the energy levels of active centers in phosphors, are quantitatively obtained here for intervalence charge transfer (IVCT) states of mixed valence pairs and metal-to-metal charge transfer (MMCT) states of heteronuclear pairs, in solid hosts. The procedure relies on vibrational frequencies and excitation energies of single-ion active centers, and on differences between ion-ligand distances of the donor and the acceptor, which are attainable empirically or through ab initio calculations. The configuration coordinate diagrams of the Yb(2+)/Yb(3+) mixed-valence pair in Yb-doped YAG and the Ce(3+)/Yb(3+) heteronuclear pair in Ce,Yb-codoped YAG, are obtained and described. They are drawn from empirical data of the single-ions and their usefulness is discussed. The first diagram suggests that IVCT states of Yb(2+)/Yb(3+) pairs may play an important role in the quenching of the Yb(3+) emission and it provides the details of the quenching mechanism. The second diagram supports the interpretation recently given for the energy transfer from Ce(3+) to Yb(3+) in Ce,Yb-codoped YAG via a MMCT Ce(4+)-Yb(2+) state and it provides the details. The analyses of the two diagrams suggest the formation of Yb(2+)/Yb(3+) pairs after the Ce(3+)-to-Yb(3+) MMCT, which is responsible for the temperature quenching of the Yb(3+) emission excited via Ce(3+) (4f -> 5d) absorption in Ce,Yb-codoped YAG. PMID- 26159814 TI - Assessing resilience in adolescence: the Spanish adaptation of the Adolescent Resilience Questionnaire. AB - BACKGROUND: The concept and assessment of resilience have attracted considerable attention in recent years, but none of the instruments developed to measure resilience in adolescents have been adapted to the Spanish context. The Adolescent Resilience Questionnaire (ARQ) provides a comprehensive and multidimensional assessment of the resources associated with resilience in adolescents. METHODS: This study analyzes the psychometric properties of the ARQ. Participants included a community sample of 1101 Spanish adolescents (53.5 % boys) aged 12-17 years (M = 14.51; SD = 1.755). RESULTS: Results confirm the factor structure based on 12 scales. Internal consistency was generally adequate (between .60 and .84), although the unacceptable coefficient for the Empathy/Tolerance scale (alpha = .38) means that this scale needs to be revised for the Spanish context. Relationships between ARQ scales and psychopathology were in the expected direction and magnitude. Some gender differences were observed, with higher scores for boys on Confidence and Negative cognition. CONCLUSIONS: The Spanish version of the ARQ can help to identify personal characteristics associated with resilience and signs of positive engagement with family, peers, school, and the community. It can identify those adolescents most likely to show resilience in response to adversity, as well as those who may be vulnerable under situations of stress. PMID- 26159816 TI - #Learning: The use of back channel technology in multi-campus nursing education. AB - This paper reports on the results of a study into the use of microblogging technology (TodaysMeet) in large, multi-site lectures in a nursing program. The aim of this study was to investigate students' use of the technology and their perceptions of its value in stimulating engagement in a complex learning environment. The study demonstrated that students like the anonymity that the technology provided, allowing them to ask questions without fear of appearing less competent than their peers. Many of the respondents commented positively on the opportunity to engage with students and the lecturer at other campuses. While some students appreciated the opportunity to interact and have feedback from peers, others saw this as a negative aspect of the technology. This study suggests that, used appropriately, microblogging can be incorporated into large lectures to promote student participation and engagement and ultimately enhance the learning process. PMID- 26159815 TI - Whole blood microarray analysis of pigs showing extreme phenotypes after a porcine reproductive and respiratory syndrome virus infection. AB - BACKGROUND: The presence of variability in the response of pigs to Porcine Reproductive and Respiratory Syndrome virus (PRRSv) infection, and recent demonstration of significant genetic control of such responses, leads us to believe that selection towards more disease resistant pigs could be a valid strategy to reduce its economic impact on the swine industry. To find underlying molecular differences in PRRS susceptible versus more resistant pigs, 100 animals with extremely different growth rates and viremia levels after PRRSv infection were selected from a total of 600 infected pigs. A microarray experiment was conducted on whole blood RNA samples taken at 0, 4 and 7 days post infection (dpi) from these pigs. From these data, we examined associations of gene expression with weight gain and viral load phenotypes. The single nucleotide polymorphism (SNP) marker WUR10000125 (WUR) on the porcine 60 K SNP chip was shown to be associated with viral load and weight gain after PRRSv infection, and so the effect of the WUR10000125 (WUR) genotype on expression in whole blood was also examined. RESULTS: Limited information was obtained through linear modeling of blood gene differential expression (DE) that contrasted pigs with extreme phenotypes, for growth or viral load or between animals with different WUR genotype. However, using network-based approaches, molecular pathway differences between extreme phenotypic classes could be identified. Several gene clusters of interest were found when Weighted Gene Co-expression Network Analysis (WGCNA) was applied to 4 dpi contrasted with 0 dpi data. The expression pattern of one such cluster of genes correlated with weight gain and WUR genotype, contained numerous immune response genes such as cytokines, chemokines, interferon type I stimulated genes, apoptotic genes and genes regulating complement activation. In addition, Partial Correlation and Information Theory (PCIT) identified differentially hubbed (DH) genes between the phenotypically divergent groups. GO enrichment revealed that the target genes of these DH genes are enriched in adaptive immune pathways. CONCLUSION: There are molecular differences in blood RNA patterns between pigs with extreme phenotypes or with a different WUR genotype in early responses to PRRSv infection, though they can be quite subtle and more difficult to discover with conventional DE expression analyses. Co-expression analyses such as WGCNA and PCIT can be used to reveal network differences between such extreme response groups. PMID- 26159817 TI - Successful thrombolytic therapy for ST-elevation acute myocardial infarction in a patient with immune thrombocytopenic purpura. PMID- 26159818 TI - Retropharyngeal air and pneumomediastinum: a rare complication of influenza A and asthma in an adult. PMID- 26159819 TI - Serotonin syndrome associated with therapeutic metaxalone in a patient with cirrhosis. PMID- 26159820 TI - Reversible left bundle-branch block due to carbon monoxide poisoning: a case report. PMID- 26159821 TI - Slip sliding away: the need for continued discussion of the use of insulin sliding scale in hospitalized patients. PMID- 26159822 TI - Anatomic Reconstruction With a Semitendinosus Allograft for Chronic Lateral Ankle Instability. AB - BACKGROUND: The modified Brostrom procedure has been successful for most patients with chronic lateral ankle instability (CLAI); however, a subset of patients has had unsatisfactory outcomes. For those at risk of failure, anatomic reconstruction of the lateral ankle ligaments using a semitendinosus allograft to augment the modified Brostrom procedure is available. PURPOSE: To report the results of anatomic reconstruction of the lateral ankle with a semitendinosus allograft for the treatment of CLAI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This is a retrospective review of a single surgeon's experience from 2003 to 2011 in performing anatomic lateral ankle ligament reconstruction with a semitendinosus allograft for the treatment of CLAI. Of 38 patients (40 ankles), 31 (33 ankles; 82% of patients) returned for final follow up and constituted the study group. Preoperatively, all patients completed the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score (AHS) and a visual analog scale (VAS) for pain and underwent plain and stress talar tilt radiographs. At the most recent follow-up, patients were evaluated by an independent surgeon and completed the postoperative AHS, Foot-Function Index (FFI), VAS for pain, Tegner activity score, and a satisfaction survey. Patients were evaluated with plain and stress talar tilt and anterior drawer radiographs. RESULTS: At a mean follow-up of 38 +/- 30 months (range, 24-107 months), 100% of patients were completely satisfied with the procedure. AHS values significantly improved from a mean of 60.3 +/- 14.4 to 87.5 +/- 9.3 (P < .0001). VAS pain scores significantly decreased from 7.3 +/- 1.3 to 1.9 +/- 1.8 (P < .0001). Twenty-two of 31 patients (71%) either returned to or were 1 level below their previous preoperative or preinjury Tegner activity level. No patients developed arthritic changes beyond grade I on plain radiographs. On stress radiographs, the mean talar tilt decreased from 14.3 degrees +/- 5.4 degrees to 3.1 degrees +/- 2.4 degrees . The mean postoperative anterior tibiotalar translation was 1.8 +/- 1.1 mm, with no patients having greater than 5 mm of translation. CONCLUSION: Anatomic lateral ankle ligament reconstruction with a semitendinosus allograft for the treatment of CLAI leads to high patient satisfaction, decreased pain, a stable ankle without arthritic changes, and significantly improved function. PMID- 26159823 TI - Microfracture and osteochondral autograft transplantation are cost-effective treatments for articular cartilage lesions of the distal femur. AB - BACKGROUND: Multiple techniques have been suggested for the treatment of isolated knee articular cartilage injuries. For smaller lesions (<2-5 cm(2)), microfracture and osteochondral autograft transplantation (OAT) are commonly used options. With an increasing focus on health care efficiency, analyzing the cost effectiveness of treatment modalities has become increasingly important. PURPOSE/HYPOTHESIS: The purpose of this study was to analyze the costs and outcomes of microfracture and OAT to compare their cost-effectiveness. The hypothesis was that microfracture would be more cost-effective. STUDY DESIGN: Economic and decision analysis; Level of evidence, 2. METHODS: A literature search was performed to identify studies comparing microfracture and OAT for the treatment of articular cartilage lesions of the distal femur in an adult population. Data from these studies including surgical time, failure rates, revision surgeries, outcome scores, and return to athletics were then incorporated into a constructed cost model using standard accounting methodology. The model was based on actual 2013 cost figures (in US dollars) for all procedure, operating room, and instrumentation costs. RESULTS: Three studies, with a mean follow-up of 8.7 years, met the inclusion criteria of having evidence level 1 or 2 comparing microfracture and OAT. There was a cumulative 28.6% reoperation rate among patients undergoing microfracture compared with 12.5% among patients undergoing OAT. While both groups demonstrated significant improvements compared with preoperative levels, the only significant differences in any outcome score reported between the 2 procedures were the International Cartilage Repair Society (ICRS) score and patient-reported return to their previous sports activity level. While microfracture had a lower initial cost ($3100), these savings lessened over 1 year ($1843) and 10 years ($996). Microfracture was more cost-effective when comparing Lysholm and Hospital for Special Surgery scores, whereas OAT was more cost-effective when comparing Tegner and ICRS scores. There was a significantly lower cost for return to play in athletes after OAT versus microfracture at 1 year ($11,428 vs $16,953, respectively), 3 years ($12,856 vs $38,000, respectively), and 10 years ($32,141 vs $60,799, respectively). CONCLUSION: Published level 1 and 2 clinical studies with a 10-year follow-up demonstrated that the net cost and cost-effectiveness of microfracture and OAT are comparable for the treatment of isolated articular cartilage lesions of the distal femur. CLINICAL RELEVANCE: Given similar clinical outcomes, microfracture and OAT are both viable, cost-effective first-line treatment options for these injuries. PMID- 26159824 TI - A Need for More Palliative Focused Care: A Survey of Colorado Skilled Care Facilities. PMID- 26159825 TI - Health professionals generally have more restrictive attitudes towards assisted dying in dementia than the public. PMID- 26159826 TI - Male victims of physical partner violence have poorer physical and mental health than men of the general population. PMID- 26159827 TI - Decrease of miR-146a is associated with the aggressiveness of human oral squamous cell carcinoma. AB - With the aim to identify microRNAs that may contribute to oral squamous cell carcinoma (OSCC) progression, we compared the microRNA expression profiles of two related cell lines that form tumors with differential aggressiveness. A panel of 28 microRNAs was found to be more than 1.5-fold altered, among which miR-146a was the most significantly changed (-4.6-fold). Loss of miR-146a expression was validated in human high-grade tumors, while normal oral mucosa retained expression, using fluorescence in situ hybridization on a tissue microarray. Restoration of miR-146a in SCC25 and UMSCC1 cells decreased in vitro invasive activity, suppressed tumor growth in vivo, and decreased the incidence of UMSCC1 lung metastasis. The transcription factor Sox2 was found to be a putative target of miR-146a. In conclusion, the loss or decrease of miR-146a is a new feature that is associated with more aggressive behaviour in oral squamous carcinoma. PMID- 26159829 TI - Reversible and non-reactive cellulose separations from ionic liquid mixtures with compressed carbon dioxide. AB - A novel physical (non-reactive) separation of cellulose from an ionic liquid (IL)/cosolvent mixture by compressed carbon dioxide is presented. The precipitation is completely reversible and rapid within small changes of pressure i.e. liquid phase CO2 composition. High pressure phase equilibrium, high pressure NMR, and solid state NMR have been utilized to understand the separation phenomena. PMID- 26159828 TI - Behavioral and pharmacological investigation of anxiety and maternal responsiveness of postpartum female rats in a pup elevated plus maze. AB - The present study investigated the validity of a novel pup-based repeated elevated plus maze task to detect reduced anxiety and increased maternal responsiveness in postpartum female rats and explored the roles of dopamine D2, serotonin transporter and GABA/benzodiazepine receptors in the mediation of these processes. Sprague-Dawley postpartum or nulliparous female rats were tested 4 times every other day on postpartum days 4, 6 and 8 in an elevated plus maze with 4 pups or 4 pup-size erasers placed on each end of the two open arms. When tested with erasers, untreated postpartum mother rats entered the open arms proportionally more than nulliparous rats. They also tended to spend more time in the open arms, indicating reduced anxiety. When tested with pups, postpartum rats retrieved pups into the closed arms, entered the open arms and closed arms more and had a higher moving speed than nulliparous rats, indicating increased maternal responsiveness. Both haloperidol (0.1 or 0.2 mg/kg, sc) and fluoxetine (5 or 10 mg/kg, ip) dose- and time-dependently decreased the percentage of time spent in the open arms and speed, but did not affect the percentage of open arm entries. Diazepam (1.0 or 2.0 mg/kg, ip) did not affect pup retrieval, open arm time/entry in lactating rats. Thus, the percentage of open arm entries appears to be the most sensitive measure of anxiety in postpartum female rats, while speed could be used to index maternal responsiveness to pups, which are likely mediated by the dopamine D2 and serotonin transporter systems. PMID- 26159830 TI - Estradiol increases IP3 by a nongenomic mechanism in the smooth muscle cells from the rat oviduct. AB - Estradiol (E2) accelerates egg transport by a nongenomic action, requiring activation of estrogen receptor (ER) and successive cAMP and IP3 production in the rat oviduct. Furthermore, E2 increases IP3 production in primary cultures of oviductal smooth muscle cells. As smooth muscle cells are the mechanical effectors for the accelerated oocyte transport induced by E2 in the oviduct, herein we determined the mechanism by which E2 increases IP3 in these cells. Inhibition of protein synthesis by Actinomycin D did not affect the E2-induced IP3 increase, although this was blocked by the ER antagonist ICI182780 and the inhibitor of phospholipase C (PLC) ET-18-OCH3. Immunoelectron microscopy for ESR1 or ESR2 showed that these receptors were associated with the plasma membrane, indicating compatible localization with E2 nongenomic actions in the smooth muscle cells. Furthermore, ESR1 but not ESR2 agonist mimicked the effect of E2 on the IP3 level. Finally, E2 stimulated the activity of a protein associated with the contractile tone, calcium/calmodulin-dependent protein kinase II (CaMKII), in the smooth muscle cells. We conclude that E2 increases IP3 by a nongenomic action operated by ESR1 and that involves the activation of PLC in the smooth muscle cells of the rat oviduct. This E2 effect is associated with CaMKII activation in the smooth muscle cells, suggesting that IP3 and CaMKII are involved in the contractile activity necessary to accelerate oviductal egg transport. PMID- 26159831 TI - Distinct profiles of human embryonic stem cell metabolism and mitochondria identified by oxygen. AB - Oxygen is a powerful regulator of cell function and embryonic development. It has previously been determined that oxygen regulates human embryonic stem (hES) cell glycolytic and amino acid metabolism, but the effects on mitochondria are as yet unknown. Two hES cell lines (MEL1, MEL2) were analyzed to determine the role of 5% (physiological) and 20% (atmospheric) oxygen in regulating mitochondrial activity. In response to extended physiological oxygen culture, MEL2 hES cells displayed reduced mtDNA content, mitochondrial mass and expression of metabolic genes TFAM, NRF1, PPARa and MT-ND4. Furthermore, MEL2 hES cell glucose consumption, lactate production and amino acid turnover were elevated under physiological oxygen. In stark contrast, MEL1 hES cell amino acid and carbohydrate use and mitochondrial function were relatively unaltered in response to oxygen. Furthermore, differentiation kinetics were delayed in the MEL1 hES cell line following BMP4 treatment. Here we report the first incidence of metabolic dysfunction in a hES cell population, defined as a failure to respond to oxygen concentration through the modulation of metabolism, demonstrating that hES cells can be perturbed during culture despite exhibiting the defining characteristics of pluripotent cells. Collectively, these data reveal a central role for oxygen in the regulation of hES cell metabolism and mitochondrial function, whereby physiological oxygen promotes glucose flux and suppresses mitochondrial biogenesis and gene expression. PMID- 26159832 TI - Resistin is a survival factor for porcine ovarian follicular cells. AB - Previously, we demonstrated the expression of resistin in the porcine ovary, the regulation of its expression and its direct effect on ovarian steroidogenesis. The objective of this study was to examine the effect of resistin on cell proliferation and apoptosis in a co-culture model of porcine granulosa and theca cells. First, we analysed the effect of resistin at 1 and 10 ng/ml alone or in combination with FSH- and IGF1 on ovarian cell proliferation with an alamarBlue assay and protein expression of cyclins A and B using western blot. Next, the mRNA and protein expression of selected pro-apoptotic and pro-survival regulators of cell apoptosis, caspase-9, -8 and -3 activity and DNA fragmentation using real time PCR, western blot, fluorescent assay and an ELISA kit, respectively, were analysed after resistin treatment. Furthermore, we determined the effect of resistin on the protein expression of ERK1/2, Stat and Akt kinase. Using specific inhibitors of these kinases, we also checked caspase-3 activity and protein expression. We found that resistin, at both doses, has no effect on cell proliferation. The results showed that resistin decreased pro-apoptotic genes, which was confirmed on protein expression of selected factors. We demonstrate an inhibitory effect of resistin on caspase activity and DNA fragmentation. Finally, resistin stimulated phosphorylation of the ERK1/2, Stat and Akt and kinases inhibitors reversed resistin action on caspase-3 activity and protein expression to control. All of these results showed that resistin has an inhibitory effect on porcine ovarian cell apoptosis by activation of the MAPK/ERK, JAK/Stat and Akt/PI3 kinase signalling pathways. PMID- 26159833 TI - Dnmt3l-knockout donor cells improve somatic cell nuclear transfer reprogramming efficiency. AB - Nuclear transfer (NT) is a technique used to investigate the development and reprogramming potential of a single cell. DNA methyltransferase-3-like, which has been characterized as a repressive transcriptional regulator, is expressed in naturally fertilized egg and morula/blastocyst at pre-implantation stages. In this study, we demonstrate that the use of Dnmt3l-knockout (Dnmt3l-KO) donor cells in combination with Trichostatin A treatment improved the developmental efficiency and quality of the cloned embryos. Compared with the WT group, Dnmt3l KO donor cell-derived cloned embryos exhibited increased cell numbers as well as restricted OCT4 expression in the inner cell mass (ICM) and silencing of transposable elements at the blastocyst stage. In addition, our results indicate that zygotic Dnmt3l is dispensable for cloned embryo development at pre implantation stages. In Dnmt3l-KO mouse embryonic fibroblasts, we observed reduced nuclear localization of HDAC1, increased levels of the active histone mark H3K27ac and decreased accumulation of the repressive histone marks H3K27me3 and H3K9me3, suggesting that Dnmt3l-KO donor cells may offer a more permissive epigenetic state that is beneficial for NT reprogramming. PMID- 26159835 TI - The Role of Sexual Orientation in the Victimization and Recovery of Sexual Assault Survivors. AB - Few studies examine the sexual violence victimization and recovery of nonheterosexuals. Limited available research suggests that lesbian and bisexual women are at increased risk for sexual violence and experience more recovery problems following assault than heterosexuals. We examine differences by sexual orientation in victimization, recovery, and social reactions as well as whether racial differences relate to recovery in female sexual assault survivors (N = 1,863) from the community. Bisexual women emerged as a distinct group from heterosexual women with greater recovery problems and experienced greater impact of social reactions. Black sexual minority women also had more negative outcomes than White sexual minority women. Results suggest that differences in sexual orientation and race relate to poorer recovery, especially for survivors with multiple marginalized identities. PMID- 26159834 TI - Smartphone apps to improve fitness and increase physical activity among young people: protocol of the Apps for IMproving FITness (AIMFIT) randomized controlled trial. AB - BACKGROUND: Physical activity is a modifiable behavior related to many preventable non-communicable diseases. There is an age-related decline in physical activity levels in young people, which tracks into adulthood. Common interactive technologies such as smartphones, particularly employing immersive features, may enhance the appeal and delivery of interventions to increase levels of physical activity in young people. The primary aim of the Apps for IMproving FITness (AIMFIT) trial is to evaluate the effectiveness of two popular "off-the shelf" smartphone apps for improving cardiorespiratory fitness in young people. METHODS/DESIGN: A three-arm, parallel, randomized controlled trial will be conducted in Auckland, New Zealand. Fifty-one eligible young people aged 14-17 years will be randomized to one of three conditions: 1) use of an immersive smartphone app, 2) use of a non-immersive app, or 3) usual behavior (control). Both smartphone apps consist of an eight-week training program designed to improve fitness and ability to run 5 km, however, the immersive app features a game-themed design and adds a narrative. Data are collected at baseline and 8 weeks. The primary outcome is cardiorespiratory fitness, assessed as time to complete the one mile run/walk test at 8 weeks. Secondary outcomes are physical activity levels, self-efficacy, enjoyment, psychological need satisfaction, and acceptability and usability of the apps. Analysis using intention to treat principles will be performed using regression models. DISCUSSION: Despite the proliferation of commercially available smartphone applications, there is a dearth of empirical evidence to support their effectiveness on the targeted health behavior. This pragmatic study will determine the effectiveness of two popular "off-the-shelf" apps as a stand-alone instrument for improving fitness and physical activity among young people. Adherence to app use will not be closely controlled; however, random allocation of participants, a heterogeneous group, and data analysis using intention to treat principles provide internal and external validity to the study. The primary outcome will be objectively assessed with a valid and reliable field-based test, as well as the secondary outcome of physical activity, via accelerometry. If effective, such applications could be used alongside existing interventions to promote fitness and physical activity in this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613001030763. Registered 16 September 2013. PMID- 26159836 TI - ECONOHEALTH: Placing helminth infections of livestock in an economic and social context. AB - Livestock farming is central to global food security and to the sustainability of rural communities throughout Europe. Animal health management has a major impact on farming efficiency. Although animal health research has provided effective prevention strategies for the major endemic diseases of livestock, these strategies typically provide solutions for single infectious diseases and they are often not adequately implemented due to farm-specific constraints. We propose a concept termed "ECONOHEALTH" which aims at including the economic and social context in our understanding of the factors that drive animal health. The concept is elaborated on using the example of the major helminthic diseases of cattle in temperate climate regions (gastrointestinal nematodes, liver fluke and lungworm). By considering major diseases simultaneously and placing disease-complexes in an economic and a social context, we believe that insights will be generated upon which more integrated, situation-adapted and thus more effective prevention strategies can be devised. PMID- 26159837 TI - Development of a high-throughput in vitro intestinal lipolysis model for rapid screening of lipid-based drug delivery systems. AB - PURPOSE: To develop a high-throughput in vitro intestinal lipolysis (HTP) model, without any means of pH-stat-titration, to enable a fast evaluation of lipid based drug delivery systems (LbDDS). MATERIAL AND METHOD: The HTP model was compared to the traditionally used dynamic in vitro lipolysis (DIVL) model with regard to the extent of lipid digestion and drug distribution of two poorly soluble model drugs (cinnarizine and danazol), during digestion of three LbDDS (LbDDS I-III). RESULT: The HTP model was able to maintain pH around 6.5 during digestion, without the addition of NaOH to neutralize the free fatty acids (FFAs), due to an increased buffer capacity. Cinnarizine was primarily located in the aqueous phase during digestion of all three LbDDS and did not differ significantly between the two models. The distribution of danazol varied from formulation to formulation, but no significant difference between the models was observed. The triacylglycerides (TAG) in LbDDS III were digested to the same extent in both models, whereas the TAG present in LbDDS II was digested slightly less in the HTP model. No TAG was present in LbDDS I and digestion was therefore not analyzed. CONCLUSION: The HTP model is able to predict drug distribution during digestion of LbDDS containing poorly water soluble drugs in the same manner as the DIVL model. Thus the HTP model might prove applicable for high throughput evaluation of LbDDS in e.g. 96 well plates or small scale dissolution equipment. PMID- 26159838 TI - Controlled release formulations of risperidone antipsychotic drug in novel aliphatic polyester carriers: Data analysis and modelling. AB - In the present study a series of biodegradable and biocompatible poly(epsilon caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37 degrees C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR). PMID- 26159839 TI - Chaperone-assisted protein aggregate reactivation: Different solutions for the same problem. AB - The oligomeric AAA+ chaperones Hsp104 in yeast and ClpB in bacteria are responsible for the reactivation of aggregated proteins, an activity essential for cell survival during severe stress. The protein disaggregase activity of these members of the Hsp100 family is linked to the activity of chaperones from the Hsp70 and Hsp40 families. The precise mechanism by which these proteins untangle protein aggregates remains unclear. Strikingly, Hsp100 proteins are not present in metazoans. This does not mean that animal cells do not have a disaggregase activity, but that this activity is performed by the Hsp70 system and a representative of the Hsp110 family instead of a Hsp100 protein. This review describes the actual view of Hsp100-mediated aggregate reactivation, including the ATP-induced conformational changes associated with their disaggregase activity, the dynamics of the oligomeric assembly that is regulated by its ATPase cycle and the DnaK system, and the tight allosteric coupling between the ATPase domains within the hexameric ring complexes. The lack of homologs of these disaggregases in metazoans has suggested that they might be used as potential targets to develop antimicrobials. The current knowledge of the human disaggregase machinery and the role of Hsp110 are also discussed. PMID- 26159840 TI - Fetuin-A as a predicator of sarcopenic left ventricular dysfunction. AB - Sarcopenia is an aging condition involving low muscle mass and function. Fetuin-A (FetA) appears to be a factor for body composition remodeling. We hypothesized that age increases FetA levels and deteriorates the myocardial function by affecting diastolic function, especially in people with sarcopenia. We enrolled 541 asymptomatic elderly (>= 65 years) patients. Compared with non-sarcopenic population, FetA levels were significantly elevated in the ninety-two (17%) patients (79 +/- 6 years; male: 34.7%) diagnosed with sarcopenia (621.1 +/- 140.7 vs. 697.3 +/- 179.6 MUg/ml, < 0.001). Sarcopenic left ventricular dysfunction (S LVD) was defined by the coexistence of sarcopenia and systolic impairment (LVEF < 50%) and 23 (4.3%) of them met the criteria. Patients with S-LVD showed relatively reduced systolic heart function, higher end-diastolic pressure and a higher FetA level (all p < 0.001) than did those with sarcopenia but without LV dysfunction (S-NLVD). Conversely, in the group without sarcopenia, FetA levels were similar regardless of systolic function. Multivariable logistic regression showed that older age, impaired diastolic function, and higher FetA levels were significantly associated with S-LVD. In conclusion, we found that FetA was significantly higher in elderly patients with sarcopenia, which was associated with impaired diastolic and systolic functions. PMID- 26159841 TI - Effect of Atorvastatin on Serum Levels of Total Cholesterol and High-Sensitivity C-reactive Protein in High-Risk Patients with Atrial Fibrillation in Asia. AB - PURPOSE: The aim of this meta-analysis was to investigate the effects of atorvastatin on serum levels of high-sensitivity C-reactive protein (hs-CRP) and total cholesterol in atrial fibrillation (AF) patients in Asia. METHODS: By searching English and Chinese language-based electronic databases (ie, PubMed, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Wanfang database, China National Knowledge Infrastructure, and VIP database), we identified 13 studies relevant to our topic of interest. Data were collected from the 13 studies and analyzed with Comprehensive Meta-Analysis software (version 2.0, Biostat Inc., Englewood, New Jersey). FINDINGS: Initially, our database searches retrieved 356 studies (45 in English, 311 in Chinese). Thirteen studies were selected for the meta-analysis following stringent criteria. The data included 1239 patients with AF, of whom 634 were treated with atorvastatin and included in the treatment group, and 605 patients were treated with conventional treatment and included in the control group. The results of our meta-analysis suggested that the serum levels of hs-CRP (mg/L) and total cholesterol (mmol/L) in the treatment group were significantly lower than those of the control group (hs-CRP: standardized mean difference = 0.962; 95% CI, 0.629-1.295, P < 0.001; total cholesterol: standardized mean difference = 1.400; 95% CI, 0.653-2.146, P < 0.001). IMPLICATIONS: The findings of this study suggest that atorvastatin may be very effective in decreasing serum levels of hs-CRP and total cholesterol to prevent cardiovascular events. PMID- 26159842 TI - Anatomic total shoulder arthroplasty for patients receiving workers' compensation. AB - BACKGROUND: Studies have demonstrated that receiving workers' compensation (WC) benefits can be a negative predictor of outcomes after orthopedic procedures. This study compares postoperative outcomes of anatomic total shoulder arthroplasty (TSA) between patients receiving WC benefits and a control group that did not. METHODS: A cohort of 13 consecutive TSA patients with WC benefits were compared with a control group of 63 consecutive patients with a minimum of 2 years of follow-up during the same period. Patient demographics, American Shoulder and Elbow Surgeons scores, 12-Item Short Form Health Survey scores, return to work status, and time out of work were evaluated. RESULTS: The WC TSA cohort consisted of 13 men and no women with a mean age of 55.9 years. Twelve of the 13 were laborers. The TSA control group consisted of 36 men and 27 women with a mean age of 63.2 years (P = .01). The American Shoulder and Elbow Surgeons scores at final follow-up were significantly lower in the WC cohort (73.6) compared with the control group (86.6; P = .01). However, the 12-Item Short Form Health Survey physical and mental component summary scores were not significantly different (P = .09 and P = .6). Only 4 of the 13 WC patients returned to work. CONCLUSION: Compared with a non-WC population, patients with WC who received an anatomic TSA are more likely to be male, younger, and a laborer. Outcomes are generally excellent and better than those of other WC shoulder surgery cohorts in the literature; however, the outcomes are relatively worse than in the non-WC TSA patients. A significant number of WC patients are unable to return to work after TSA. PMID- 26159843 TI - Evaluation of body weight-based vancomycin therapy and the incidence of nephrotoxicity: a retrospective study in the northwest of China. AB - OBJECTIVE: To identify specific risk factors of vancomycin-induced nephrotoxicity in China, as the relationship between vancomycin therapy (dosing and trough concentration monitoring) and nephrotoxicity has been the subject of critical debate. METHODS: The cases of 90 critically ill patients who received vancomycin therapy in Xijing Hospital in the northwest of China between March 2014 and January 2015 were reviewed retrospectively. Vancomycin dosing, blood serum trough concentration, and other independent risk factors associated with nephrotoxicity were evaluated in a multivariable model. RESULTS: Among the 90 critically ill patients, 59 were males; mean age was 46.3 years. The indications for vancomycin use were methicillin-resistant Staphylococcus aureus-associated pneumonia, central nervous system infection, and bacteremia. Clinical pharmacists prescribed weight-based dosing, ranging from 20 to 45mg/kg/day. Fourteen (15.6%) patients developed nephrotoxicity, with serum creatinine elevated significantly from a mean (standard deviation) of 90.0 (18.8) MUmol/l to 133.8 (63.2) MUmol/l (p = 0.015). It was found that those with a vancomycin dosage >38mg/kg/day (50.0% vs. 11.3%, p = 0.004) and a vancomycin serum trough concentration >20mg/l (57.1% vs. 12.0%, p = 0.01) were more likely to develop nephrotoxicity. CONCLUSION: The data from this study indicate that a vancomycin dosage >38mg/kg/day and a serum trough level >20mg/l are both independent factors associated with the development of nephrotoxicity, suggesting that renal function should be monitored closely during vancomycin treatment. PMID- 26159844 TI - Brucellosis in pregnancy: clinical aspects and obstetric outcomes. AB - OBJECTIVE: Brucellosis is a zoonosis with high morbidity in humans. This disease has gained interest recently due to its re-emergence and potential for weaponization. Pregnant women with this disease can develop severe complications. Its association with adverse obstetric outcomes is not clearly understood. The objective of this study was to describe the obstetric outcomes of brucellosis in pregnancy. METHODS: Cases of pregnant women with active brucellosis seen at the Hospital Nacional Cayetano Heredia from 1970 to 2012 were reviewed. Diagnostic criteria were a positive agglutination test and/or positive blood/bone marrow culture. Presentation and outcomes data were collected. The Chi-square test was used for nominal variables. A p-value of <0.05 indicated significance. RESULTS: One hundred and one cases were included; 27.7% had a threatened abortion/preterm labor, 12.8% experienced spontaneous abortion, 13.9% preterm delivery, 8.1% fetal death, and 1.1% congenital malformations. There was one maternal death secondary to severe sepsis. After delivery, neonatal death occurred in 8.1%, low birth weight in 14.5%, and congenital brucellosis in 6.4%. The most common treatment was aminoglycosides plus rifampicin (42.2% of cases). Complication rates decreased if treatment was started within 2 weeks of presentation (p < 0.001). CONCLUSIONS: This is the largest series of brucellosis in pregnancy reported in the literature. Brucella presents adverse obstetric outcomes including fetal and maternal/neonatal death. Cases with unexplained spontaneous abortion should be investigated for brucellosis. Prompt treatment is paramount to decrease the devastating outcomes. PMID- 26159845 TI - Conventional and molecular methods in the diagnosis of community-acquired diarrhoea in children under 5 years of age from the north-eastern region of Poland. AB - OBJECTIVES: The purpose of this study was to determine the main causative agents of community-acquired acute diarrhoea in children using conventional methods and PCR. METHODS: Stool samples were collected from 100 children under 5 years of age with acute diarrhoea during the autumn-winter period of 2010-2011. Rotaviruses and adenoviruses were detected by the stool antigen immunoassay, and Salmonella spp, Campylobacter spp, Shigella spp, Yersinia enterocolitica, Yersinia pseudotuberculosis, Clostridium difficile, enterotoxigenic Bacteroides fragilis (ETBF), and diarrhoeagenic Escherichia coli were detected by culture methods and PCR. RESULTS: Overall, enteropathogens were identified in 73% of the children. Bacteria, viruses, and mixed infections were noted in 37%, 24%, and 12% of diarrhoeal cases, respectively. The most common enteric pathogens were rotaviruses (31%), followed by C. difficile (17%), Campylobacter jejuni (13%), Salmonella spp (11%), and atypical enteropathogenic Escherichia coli (aEPEC) strains (10%). Compared with culture methods, PCR increased the overall detection frequency of the bacterial enteropathogens by 4%. CONCLUSIONS: The high prevalence of Campylobacter jejuni suggests that the number of campylobacteriosis cases in Poland may be underestimated; this pathogen should be investigated routinely in children with diarrhoea. Moreover, C. difficile might be considered a causative or contributing agent of diarrhoea in 14.8% of children aged >1 year. PMID- 26159846 TI - Molecular characterization of Leptospira sp by multilocus variable number tandem repeat analysis (MLVA) from clinical samples: a case report. AB - Leptospirosis is a zoonotic infection for which diagnosis is difficult. It has appeared as a global emerging infectious disease over recent years. Genotype determination often requires a Leptospira strain obtained by culture, which is a long and fastidious technique. A method based on multilocus variable number tandem repeat analysis (MLVA) to determine the genotype of Leptospira interrogans, performed directly on blood or urine samples, is proposed. This method was applied to a fatal case of leptospirosis for which the geographical origin of infection was unknown. This technique will allow a genotype to be obtained for L. interrogans, even when cultures remain negative. PMID- 26159847 TI - Nosocomial Gram-negative bacteremia in intensive care: epidemiology, antimicrobial susceptibilities, and outcomes. AB - OBJECTIVES: To describe the epidemiology, antimicrobial susceptibilities, treatment, and outcomes of intensive care unit (ICU)-acquired Gram-negative bacteremia. METHODS: Patients with ICU-acquired Gram-negative bacteremia from 2004 to 2012 were reviewed retrospectively. Independent predictors of mortality were examined using multivariable Cox regression. RESULTS: Seventy-eight cases of ICU-acquired Gram-negative bacteremia occurred in 74 patients. The infection rate was 0.97/1000 patient-days. Mean patient age was 55 years, 62% were male. The most common admission diagnoses were respiratory failure (34%) and sepsis/septic shock (45%). Mortality was 35% at 30 days. The most common source of bacteremia was pneumonia (33%). Of 83 Gram-negative isolates, Escherichia coli (20%) and Pseudomonas aeruginosa (18%) were most common. For aerobic isolates, susceptibilities to ciprofloxacin (61%) and piperacillin/tazobactam (68%) were low. For pseudomonal isolates, susceptibilities to ciprofloxacin (53%), piperacillin/tazobactam (67%), and imipenem (53%) were equally disappointing. Adequate empiric antimicrobial therapy was prescribed in 85% of bacteremia cases. On multivariable analysis, adequate empiric therapy (adjusted hazard ratio (aHR) 0.38, 95% confidence interval (CI) 0.16-0.89), immune suppression (aHR 3.4, 95% CI 1.4-8.3), and coronary artery disease (aHR 4.5, 95% CI 1.7-11.9) were independently associated with 30-day mortality. CONCLUSIONS: ICU-acquired Gram negative bacteremia is associated with high mortality. Resistance to ciprofloxacin, piperacillin/tazobactam, and carbapenems was common. Coronary artery disease, immune suppression, and inadequate empiric antimicrobial therapy were independently associated with increased mortality. PMID- 26159848 TI - Optical Estimation of Beta 2 Microglobulin during Hemodiafiltration - Does It Work? AB - BACKGROUND: Currently, urea reduction seems to be the most widely used dialysis dose parameter. The aim of this study was to investigate the possibility to monitor beta 2-microglobulin (beta2-M) elimination by utilizing the ultraviolet (UV) absorbance of spent dialysate. METHODS: Blood and spent dialysate were collected during two week's sessions in 8 patients, one week in hemodialysis (HD) and one in hemodiafiltration (HDF). Correlation analysis between UV-wavelengths and concentrations of solutes in spent dialysate was performed. The reduction ratio (RR) of concentrations in blood, dialysate and UV-absorbance were compared. RESULTS: Differences between HD and HDF were discovered in wavelength correlation maxima for the solutes. Relative error in RR (%) was larger (p < 0.05) for beta2 M than for the other solutes. The most reasonable explanation is that beta2-M does not absorb UV-radiation; instead, the absorbance of surrogate substances is measured. CONCLUSION: A high correlation between UV-absorbance and beta2-M can be achieved for HDF but not for HD. Still, UV-absorbance could perhaps be used in solely HDF mode for estimation of beta2-M removal. PMID- 26159849 TI - Overexpression of SOX2 is involved in paclitaxel resistance of ovarian cancer via the PI3K/Akt pathway. AB - Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Sex-determining region Y-box 2 (SOX2) is of vital importance in the regulation of stem cell proliferation and carcinogenesis. The aim of this study was to evaluate the role of SOX2 in ovarian cancer tumorigenesis and paclitaxel resistance. In the present study, the expression of SOX2 was examined by immunohistochemistry (IHC) and real-time PCR in 40 clinical samples and in SKOV3 cells and SKOV3/TAX cells (paclitaxel-resistant human ovarian adenocarcinoma cell line). The effects of SOX2 knockdown on ovarian cancer cell proliferation, migration, and invasion were also studied. The IHC and real-time PCR results showed that the difference of SOX2 expression between ovarian cancer and the adjacent non-tumorous ovarian tissues was statistically significant. Western blot analysis revealed that the PI3K/Akt signaling pathway was inhibited in cells overexpressing SOX2. Western blot analysis showed that the SOX2 protein was overexpressed in paclitaxel-resistant cells and weakly detectable in paclitaxel-sensitive cells. SOX2 silencing significantly potentiated apoptosis induced by paclitaxel in SKOV3-TR with SOX2 knockdown compared to SKOV3-TR transfected with control small interfering RNA (siRNA). Our work indicates SOX2 will become both a rational indicator of ovarian cancer prognosis and a promising target for ovarian cancer gene therapy. PMID- 26159850 TI - The clinical and prognostic significance of midkine in breast cancer patients. AB - Midkine overexpression has been shown to be a tumor biomarker in several types of human cancer, but little is known about the clinical significance of midkine in breast cancer patients. The aim of this study was to analyze the expression of midkine in breast cancer and its correlation with clinicopathological characteristics, including breast cancer patient's survival. The expression status of midkine in breast cancer from Gene Expression Omnibus (GEO accession number: GDS3853) was observed initially. Furthermore, the expression of midkine messenger RNA (mRNA) and protein was examined in breast cancer and normal mammary tissues through real-time PCR and immunohistochemistry. Moreover, the relationship of midkine protein expression with clinical characteristics of 170 breast cancer patients was analyzed by immunohistochemistry. In our results, midkine was up-expressed in breast cancer tissues compared with normal mammary tissues in microarray data (GDS3853). Midkine mRNA and protein expression was significantly increased in breast cancer tissues than in normal mammary tissues. By immunohistochemistry, high levels of midkine protein were positively associated with the status of clinical stage, T classification, N classification, and M classification in breast cancer patients. Furthermore, midkine overexpression was an independent poor prognostic indicator for the survival of patients with breast cancer. In conclusion, overexpression of midkine protein serves as an unfavorable prognostic biomarker in breast cancer patients. PMID- 26159851 TI - Clinical and prognostic value of MET gene copy number gain and chromosome 7 polysomy in primary colorectal cancer patients. AB - We aimed to explore the clinical and prognostic influence of numeric alterations of MET gene copy number (GCN) and chromosome 7 (CEP7) CN in colorectal cancer (CRC) patients. MET GCN and CEP7 CN were investigated in tissue arrayed tumors from 170 CRC patients using silver in situ hybridization (SISH). MET GCN gain was defined as >=4 copies of MET, and CEP7 polysomy was prespecified as >=3 copies of CEP7. Additionally, MET messenger RNA (mRNA) transcription was evaluated using mRNA ISH and compared with MET GCN. MET GCN gain was observed in 14.7 % (25/170), which correlated with advanced stage (P = 0.037), presence of distant metastasis (P = 0.006), and short overall survival (OS) (P = 0.009). In contrast, CEP7 polysomy was found in 6.5 % (11/170), which was related to tumor location in the left colon (P = 0.027) and poor OS (P = 0.029). MET GCN positively correlated with CEP7 CN (R = 0.659, P < 0.001) and mRNA transcription (R = 0.239, P = 0.002). Of note, MET GCN gain and CEP7 polysomy were also associated with poor OS (P = 0.016 and P < 0.001, respectively) in stage II/III CRC patients (n = 123). In multivariate analysis, CEP7 polysomy was an independent prognostic factor for poor OS in all patients (P = 0.009; hazard ratio [HR], 2.220; 95 % confidence interval [CI], 1.233-3.997) and in stage II/III CRC patients (P < 0.001; HR, 20.781; 95 % CI, 4.600-93.882). MET GCN gain and CEP7 polysomy could predict a poor outcome in CRC patients, especially CEP7 polysomy has the most powerful prognostic impact in stage II/III CRC patients. PMID- 26159852 TI - Antineoplastic effects of Rhodiola crenulata treatment on B16-F10 melanoma. AB - Melanoma is an aggressive form of skin cancer with limited treatment options for advanced stage disease. Early detection and wide surgical excision remain the initial mode of treatment for primary tumors thus preventing metastases and leading to improved prognosis. Through this work, we have evaluated the antineoplastic effects of Rhodiola crenulata (R. crenulata) root extracts on the B16-F10 melanoma cell line, both in vitro and in vivo. We observed that R. crenulata treatment resulted in increased cell death as well as a reduction in tumor cell proliferation and migration in vitro. Additionally, we observed that R. crenulata decreased the expression of integrin beta1 and vimentin and increased the expression of E-cadherin. Further, in mice treated with a topical R. crenulata-based cream therapy, tumors were more likely to have a radial growth pattern, a reduction in mitotic activity, and an increase in tumor necrosis. We also observed that mice drinking water supplemented with R. crenulata displayed a reduction of metastatic foci in disseminated models of melanoma. Collectively, these findings suggest that R. crenulata exhibits striking antitumorigenic and antimetastatic properties and that this extract may harbor potential novel adjuvant therapy for the treatment of melanoma. PMID- 26159853 TI - Downregulation of the long noncoding RNA EGOT correlates with malignant status and poor prognosis in breast cancer. AB - Eosinophil granule ontogeny transcript (EGOT) is a long noncoding RNA involved in the regulation of eosinophil granule protein transcript expression. However, little is known about the role of EGOT in malignant disease. This study aimed to assess the potential role of EGOT in the pathogenesis of breast cancer. Quantitative real-time polymerase chain reaction was performed to detect the expression levels of EGOT in 250 breast cancerous tissues and 50 adjacent noncancerous tissues. The correlation of EGOT expression with clinicopathological features and prognosis was also analyzed. EGOT expression was lower in breast cancer compared with the adjacent noncancerous tissues (P < 0.001), and low levels of EGOT expression were significantly correlated with larger tumor size (P = 0.022), more lymph node metastasis (P = 0.020), and higher Ki-67 expression (P = 0.017). Moreover, patients with low levels of EGOT expression showed significantly worse prognosis for overall survival (P = 0.040), and this result was further validated in a larger cohort from a public database. Multivariate analysis suggested that low levels of EGOT were a poor independent prognostic predictor for breast cancer patients (HR = 1.857, 95 % CI = 1.032-3.340, P = 0.039). In conclusion, EGOT may play an important role in breast cancer progression and prognosis and may serve as a new potential prognostic target in breast cancer patients. PMID- 26159854 TI - Identification of RAB2A and PRDX1 as the potential biomarkers for oral squamous cell carcinoma using mass spectrometry-based comparative proteomic approach. AB - Despite the recent advances in diagnostic and therapeutic strategies, oral squamous cell carcinoma (OSCC) remains a major health burden. Protein biomarker discovery for early detection will help to improve patient survival rate in OSCC. Mass spectrometry-based proteomics has emerged as an excellent approach for detection of protein biomarkers in various types of cancers. In the current study, we have used 4-Plex isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun quantitative proteomic approach to identify proteins that are differentially expressed in cancerous tissues compared to normal tissues. The high-resolution mass spectrometric analysis resulted in identifying 2,074 proteins, among which 288 proteins were differentially expressed. Further, it was noticed that 162 proteins were upregulated, while 125 proteins were downregulated in OSCC-derived cancer tissue samples as compared to the adjacent normal tissues. We identified some of the known molecules which were reported earlier in OSCC such as MMP-9 (8.4-fold), ZNF142 (5.6-fold), and S100A7 (3.5-fold). Apart from this, we have also identified some novel signature proteins which have not been reported earlier in OSCC including ras-related protein Rab-2A isoform, RAB2A (4.6 fold), and peroxiredoxin-1, PRDX1 (2.2-fold). The immunohistochemistry-based validation using tissue microarray slides in OSCC revealed overexpression of the RAB2A and PRDX1 gene in 80 and 68 % of the tested clinical cases, respectively. This study will not only serve as a resource of candidate biomarkers but will contribute towards the existing knowledge on the role of the candidate molecules towards disease progression and therapeutic potential. PMID- 26159855 TI - Metabolic reprogramming as a continuous changing behavior of tumor cells. AB - Malignant cells resist microenvironment stress and migrate into surrounding tissues in order to divide with the need to adapt their metabolic program. These changes, often strengthened by the tremendous liaison between hypoxia, low glucose, and acidosis, are not yet completely understood. The aim of this perspective is to re-organize a possible comprehensive scenario useful to identify the metabolism occurring in various tumor cell subpopulations endowed with different capabilities. PMID- 26159856 TI - Landau levels and magneto-transport property of monolayer phosphorene. AB - We investigate theoretically the Landau levels (LLs) and magneto-transport properties of phosphorene under a perpendicular magnetic field within the framework of the effective k.p Hamiltonian and tight-binding (TB) model. At low field regime, we find that the LLs linearly depend both on the LL index n and magnetic field B, which is similar with that of conventional semiconductor two dimensional electron gas. The Landau splittings of conduction and valence band are different and the wavefunctions corresponding to the LLs are strongly anisotropic due to the different anisotropic effective masses. An analytical expression for the LLs in low energy regime is obtained via solving the decoupled Hamiltonian, which agrees well with the numerical calculations. At high magnetic regime, a self-similar Hofstadter butterfly (HB) spectrum is obtained by using the TB model. The HB spectrum is consistent with the LL fan calculated from the effective k.p theory in a wide regime of magnetic fields. We find the LLs of phosphorene nanoribbon depend strongly on the ribbon orientation due to the anisotropic hopping parameters. The Hall and the longitudinal conductances (resistances) clearly reveal the structure of LLs. PMID- 26159857 TI - Ubinuclein-1 confers histone H3.3-specific-binding by the HIRA histone chaperone complex. AB - Histone chaperones bind specific histones to mediate their storage, eviction or deposition from/or into chromatin. The HIRA histone chaperone complex, composed of HIRA, ubinuclein-1 (UBN1) and CABIN1, cooperates with the histone chaperone ASF1a to mediate H3.3-specific binding and chromatin deposition. Here we demonstrate that the conserved UBN1 Hpc2-related domain (HRD) is a novel H3.3 specific-binding domain. Biochemical and biophysical studies show the UBN1-HRD preferentially binds H3.3/H4 over H3.1/H4. X-ray crystallographic and mutational studies reveal that conserved residues within the UBN1-HRD and H3.3 G90 as key determinants of UBN1-H3.3-binding specificity. Comparison of the structure with the unrelated H3.3-specific chaperone DAXX reveals nearly identical points of contact between the chaperone and histone in the proximity of H3.3 G90, although the mechanism for H3.3 G90 recognition appears to be distinct. This study points to UBN1 as the determinant of H3.3-specific binding and deposition by the HIRA complex. PMID- 26159858 TI - Long Noncoding RNA MALAT-1 Can Predict Metastasis and a Poor Prognosis: a Meta Analysis. AB - Elevated expression of MALAT-1 was found in various cancers, and correlated with metastasis and prognostic. This meta-analysis collected all relevant articles and explored correlation of MALAT-1 with lymph node metastasis (LNM), distant metastasis (DM), and overall survival (OS). A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, Medline, CNKI, CBM, and the Cochrane Library. The odds ratios (OR) of LNM and DM and hazard ratio (HR) of OS were calculated to assess the association strength. Eight studies with a total of 845 patients were included in the meta-analysis. Six different types of cancer were evaluated, with 2 non-small cell lung cancer (NSCLC), 1 colorectal cancer (CRC), 1 gastric cancer (GC), 2 pancreatic cancer (PC), 1 clear cell renal cell carcinoma (ccRCC), and 1 osteosarcoma (OSA). Compared with low MALAT-1 expression, high MALAT-1 expression correlated with more LNM (OR = 2.08, 95 %CI: 1.00-4.32, p = 0.05) by a random-effects model (I (2) = 71 %, p = 0.004). A similar result was seen between MALAT-1 expression and DM, the OR was 3.52 (95 %CI: 1.06-11.71, p = 0.04) adopting a random-effects model (I (2) = 59 %, p = 0.04). Additionally, our analysis showed a poorer OS in patients with high MALAT-1 expression than those with low MALAT-1 expression (HR = 2.12, 95 %CI: 1.60-2.82, p < 0.001) adopting a random-effects model (I (2) = 56 %, p = 0.04). MALAT-1 may serve as a molecular marker for cancer metastasis and prognosis. PMID- 26159859 TI - A focus on pharmacotherapy for primary central nervous system lymphoma. AB - The prognosis of primary central nervous system lymphoma (PCNSL) is still poor compared to other diffuse large B-cell lymphomas. High-dose methotrexate-based chemotherapy plays a central role in the management of PCNSL; however, the optimal regimen has not been established thus far. Consolidating whole-brain radiotherapy is currently not routinely being performed at most centers due to lack of survival advantage in a randomized Phase III trial and increased risk of cognitive impairment. Promising results with the combination of high-dose methotrexate-based chemotherapy with the CD20 antibody rituximab and consolidating the primary chemotherapy by other non-cross-resistant conventional chemotherapy or high-dose chemotherapy followed by autologous stem cell transplantation have been reported in non-comparative studies. Results of well designed randomized trials must be awaited to better define the optimal management of PCNSL. PMID- 26159860 TI - Persistence of psychological distress and correlated factors among patients with head and neck cancer--CORRIGENDUM. PMID- 26159861 TI - Cardiac insufficiency in infants. AB - Cardiac failures in young children have shown an enormous trudge in recent past. The reason being medical community has laid more stress on cardiac insufficiency management on adult patients and has conducted a large amount of research on the management of heart failure in adults, which has given rise to significant changes in management in the last decade. However, there are far fewer studies in children and those which do exist are often small, retrospective and use a diverse range of measures to assess efficacy. Current research is being focused worldwide to deal with this life threatening problem of young patients. The present review shall enlighten the above focus of the research and will discuss latest developments in therapeutic advances like paediatric use of ace inhibitors, beta blockers in young patients for the efficient management of cardiac insufficiency. PMID- 26159862 TI - High prevalence of multiple syndemic conditions associated with sexual risk behavior and HIV infection among a large sample of Spanish- and Portuguese speaking men who have sex with men in Latin America. AB - The HIV epidemic in Latin America is highly concentrated in men who have sex with men (MSM). In the United States, multiple co-occurring psychosocial conditions have been shown to act as intertwined epidemics to potentiate HIV transmission among MSM. To date, no study has examined the role of syndemics and condomless sex among MSM in Latin America. In 2012, an online survey was conducted among members of the largest social/sexual networking website for MSM in Latin America. Participants were asked about demographics, sexual behaviors, HIV/STI diagnoses, and psychosocial well-being, including depression, suicidal ideation, hazardous alcohol use, hard drug use during sex, history of childhood/adolescent sexual abuse, intimate partner violence, and sexual compulsivity. Multivariable logistic generalized estimation equations were used to assess the relationship of syndemic factors and (1) engagement in higher risk condomless anal sex and (2) self-report of prior HIV diagnosis. Among 24,274 survey respondents, 74.6 % of the sample had at least one syndemic factor. In an additive model, syndemics were associated with increased odds of higher risk condomless anal sex, ranging from adjusted odds ratio of 1.31 (95 % CI 1.20, 1.43) for one syndemic factor to 4.06 (95 % CI 3.25, 5.09) for 6/7 syndemic factors. Similarly, syndemics were associated with increased odds of HIV infection (p < .0001). This study provides initial evidence that intertwined syndemics increase HIV risk behavior and HIV infection among MSM in Latin America. In the Latin American context, comprehensive HIV prevention interventions for MSM should be developed and tested that simultaneously address co-occurring psychosocial conditions and HIV risk. PMID- 26159864 TI - Authors' Response. PMID- 26159863 TI - Complexity of childhood sexual abuse: predictors of current post-traumatic stress disorder, mood disorders, substance use, and sexual risk behavior among adult men who have sex with men. AB - Men who have sex with men (MSM) are the group most at risk for HIV and represent the majority of new infections in the United States. Rates of childhood sexual abuse (CSA) among MSM have been estimated as high as 46 %. CSA is associated with increased risk of HIV and greater likelihood of HIV sexual risk behavior. The purpose of this study was to identify the relationships between CSA complexity indicators and mental health, substance use, sexually transmitted infections, and HIV sexual risk among MSM. MSM with CSA histories (n = 162) who were screened for an HIV prevention efficacy trial completed comprehensive psychosocial assessments. Five indicators of complex CSA experiences were created: CSA by family member, CSA with penetration, CSA with physical injury, CSA with intense fear, and first CSA in adolescence. Adjusted regression models were used to identify relationships between CSA complexity and outcomes. Participants reporting CSA by family member were at 2.6 odds of current alcohol use disorder (OR 2.64: CI 1.24-5.63), two times higher odds of substance use disorder (OR 2.1: CI 1.02-2.36), and 2.7 times higher odds of reporting an STI in the past year (OR 2.7: CI 1.04-7.1). CSA with penetration was associated with increased likelihood of current PTSD (OR 3.17: CI 1.56-6.43), recent HIV sexual risk behavior (OR 2.7: CI 1.16-6.36), and a greater number of casual sexual partners (p = 0.02). Both CSA with Physical Injury (OR 4.05: CI 1.9-8.7) and CSA with Intense Fear (OR 5.16: CI 2.5-10.7) were related to increased odds for current PTSD. First CSA in adolescence was related to increased odds of major depressive disorder. These findings suggest that CSA, with one or more complexities, creates patterns of vulnerabilities for MSM, including post-traumatic stress disorder, substance use, and sexual risk taking, and suggests the need for detailed assessment of CSA and the development of integrated HIV prevention programs that address mental health and substance use comorbidities. PMID- 26159865 TI - Conformational thermostabilisation of corticotropin releasing factor receptor 1. AB - Recent technical advances have greatly facilitated G-protein coupled receptors crystallography as evidenced by the number of successful x-ray structures that have been reported recently. These technical advances include novel detergents, specialised crystallography techniques as well as protein engineering solutions such as fusions and conformational thermostabilisation. Using conformational thermostabilisation, it is possible to generate variants of GPCRs that exhibit significantly increased stability in detergent micelles whilst preferentially occupying a single conformation. In this paper we describe for the first time the application of this technique to a member of a class B GPCR, the corticotropin releasing factor receptor 1 (CRF1R). Mutational screening in the presence of the inverse agonist, CP-376395, resulted in the identification of a construct with twelve point mutations that exhibited significantly increased thermal stability in a range of detergents. We further describe the subsequent construct engineering steps that eventually yielded a crystallisation-ready construct which recently led to the solution of the first x-ray structure of a class B receptor. Finally, we have used molecular dynamic simulation to provide structural insight into CRF1R instability as well as the stabilising effects of the mutants, which may be extended to other class B receptors considering the high degree of structural conservation. PMID- 26159866 TI - Genetic determinants associated with cfxA-positive clinical Capnocytophaga isolates. PMID- 26159867 TI - Activity of RX-P873, a novel pyrrolocytosine, against Gram-negative bacteria. PMID- 26159868 TI - Postmortem Quetiapine Reference Concentrations in Brain and Blood. AB - Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N = 36), the 10-90 percentiles for quetiapine concentrations in brain tissue were 0.030-1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10-90 percentile values were 0.007-0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brain-blood ratio 10-90 percentiles of 2.31-6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N = 5), the median value in brain tissue of 8.02 mg/kg (range 2.69-22.98 mg/kg) was more than 15 times higher than the median of the nontoxic values, and about the same relationship occurred for blood with a median of 3.19 mg/kg (range 1.00-6.90 mg/kg). The brain-blood ratios for toxic concentrations were in the range of 2.08-6.05, which correspond to those of the nontoxic concentrations. A single case, where quetiapine was ruled as the sole cause of death, a suicide by quetiapine overdose, had an even higher value of 25.74 mg/kg in brain tissue. The blood concentration was 8.99 mg/kg, giving a brain-blood ratio of 2.86. Thus, on average the brain concentrations were about four times the blood concentrations. The brain concentrations of quetiapine observed in cases, where quetiapine was unrelated to death, may serve as a reference, when evaluating postmortem cases with no blood available. The recorded concentrations, where quetiapine was contributing to death, give an indication of likely toxic concentrations. PMID- 26159869 TI - Quantifying Solvophobic Effects in Nonpolar Cohesive Interactions. AB - The hydrophobic effect plays a central role in determining the structure, activity, and properties of biomolecules and materials. In contrast, the general manifestation of this phenomenon in other solvents-the solvophobic effect although widely invoked, is currently poorly defined because of the lack of a universally accepted descriptor. Here we have used synthetic molecular balances to measure solvent effects on aromatic, aliphatic, and fluorous nonpolar interactions. Our solvent screening data combined with independent experimental measurements of supramolecular association, single-molecule folding, and bulk phase transfer energies were all found to correlate well with the cohesive energy density (ced) of the solvent. Meanwhile, other measures of solvent cohesion, such as surface tension and internal pressure, gave inferior correlations. Thus, we establish ced as a readily accessible, quantitative descriptor of solvophobic association in a range of chemical contexts. PMID- 26159870 TI - Comprehensive molecular characterization of the alpha/beta-gliadin multigene family in hexaploid wheat. AB - To characterize the structure and expression of a large multigene family of alpha/beta-gliadin genes, 90 individual alpha/beta-gliadin genes harboring a promoter region were identified in the wheat cultivar Chinese Spring. These genes were classified into eleven groups by phylogenetic analysis, and the chromosomes they were derived from were determined. Of these genes, 50 had the basic alpha/beta-gliadin domains and six conserved cysteine residues and 16, 16 and 18 of them were, respectively, located on chromosome 6A, 6B and 6D. Six genes had an additional cysteine residue, suggesting that these alpha/beta-gliadins acquired the property of binding other proteins through intermolecular disulphide bands. Expression of alpha/beta-gliadin genes in developing seeds was measured by quantitative RT-PCR using group-specific primers over 3 years. Expression patterns of these genes on the basis of accumulated temperature were similar among gene groups, whereas expression levels differed for the 3 years. The expression of most alpha/beta-gliadin and other prolamin genes was correlated with the sunshine duration. On the other hand, although all alpha/beta-gliadin genes had a common E-box within the -300 promoter region, some genes showed a particular expression pattern with respect to the sunshine duration, similarly to gene encoding high-molecular weight glutenin subunits and endosperm enzymes. These observations suggested that expression of each alpha/beta-gliadin gene is differentially regulated by multiple regulatory factors. PMID- 26159871 TI - Apparent diffusion coefficient parametric response mapping MRI for follow-up of glioblastoma. AB - OBJECTIVES: To determine the diagnostic superiority of parametric response mapping of apparent diffusion coefficient (ADCPR) for predicting glioblastoma treatment response, compared to single time point measurement. METHODS: Fifty post-treatment glioblastoma patients were enrolled. ADCPR was calculated from serial apparent diffusion coefficient (ADC) maps acquired before and at the time of first detection of an enlarged contrast-enhancing lesion on voxel-by-voxel basis. The percentage-decrease in ADCPR and tenth percentile histogram cutoff value of ADC (ADC10) were compared at subsequent 3-month and 1-year follow-ups. RESULTS: The percentage-decrease in ADCPR was significantly higher in the progression group (mean = 33.2-38.3 %) than in the stable-response group (mean = 9.7 %) at 3 months follow-up (corrected p < 0.001 for both readers). ADCPR significantly improved area under the receiver operating characteristic curve from 0.67 to 0.88 (corrected p = 0.037) and from 0.70 to 0.92 (corrected p = 0.020) for both readers, respectively, compared to ADC10 at 3-month follow-up, but did not significantly improve at 1-year follow-up. The inter-reader agreement was higher for ADCPR than ADC10 (intraclass correlation coefficient, 0.93 versus 0.86). CONCLUSION: Voxel-based ADCPR appears to be a superior imaging biomarker than ADC, particularly for predicting early tumour progression in patients with glioblastoma. KEY POINTS: * Treatment response pattern of glioblastoma was evaluated using voxel-based ADCPR and ADC10. * Voxel-based ADCPR was more accurate in predicting treatment response pattern than ADC10. * Inter-reader agreement was higher in ADCPR calculation than in ADC10 calculation. * Voxel based ADCPR can be a predictor of early treatment response pattern for glioblastoma. PMID- 26159872 TI - Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis. AB - OBJECTIVE: To assess the utility of dual-energy contrast-enhanced spectral mammography (DE-CESM) for evaluation of suspicious malignant microcalcifications. METHODS: Two hundred and fifty-six DE-CESMs were reviewed from 2012-2013, 59 cases fulfilled the following criteria and were enrolled for analysis: (1) suspicious malignant microcalcifications (BI-RADS 4) on mammogram, (2) no related mass, (3) with pathological diagnoses. The microcalcification morphology and associated enhancement were reviewed to analyse the accuracy of the diagnosis and cancer size measurements versus the results of pathology. RESULTS: Of the 59 microcalcifications, 22 were diagnosed as cancers, 19 were atypical lesions and 18 were benign lesions. Twenty (76.9 %) cancers, three (11.55 %) atypia and three (11.55 %) benign lesions revealed enhancement. The true-positive rate of intermediate- and high-concern microcalcifications was significantly higher than that of low-concern lesions (93.75 % vs. 50 %). Overall, the diagnostic sensitivity of enhancement was 90.9 %, with 83.78 % specificity, 76.92 % positive predictive value, 93.94 % negative predictive value and 86.4 % accuracy. Performance was good (AUC = 0.87) according to a ROC curve and cancer size correlation with a mean difference of 0.05 cm on a Bland-Altman plot. CONCLUSIONS: DE-CESM provides additional enhancement information for diagnosing breast microcalcifications and measuring cancer sizes with high correlation to surgicohistology. KEY POINTS: * DE-CESM provides additional enhancement information for diagnosing suspicious breast microcalcifications. * The enhanced cancer size closely correlates to microscopy by Bland-Altman plot. * DE-CESM could be considered for evaluation of suspicious malignant microcalcifications. PMID- 26159873 TI - Topically Administered Janus-Kinase Inhibitors Tofacitinib and Oclacitinib Display Impressive Antipruritic and Anti-Inflammatory Responses in a Model of Allergic Dermatitis. AB - The prevalence of allergic skin disorders has increased rapidly, and development of therapeutic agents to alleviate the symptoms are still needed. In this study, we orally or topically administered the Janus kinase (JAK) inhibitors, tofacitinib and oclacitinib, in a mouse model of dermatitis, and compared the efficacy to reduce the itch and inflammatory response. In vitro effects of JAK inhibitors on bone marrow-derived dendritic cells (BMDCs) were analyzed. For the allergic dermatitis model, female BALB/c mice were sensitized and challenged with toluene-2,4-diisocyanate (TDI). Each JAK inhibitor was orally or topically applied 30 minutes before and 4 hours after TDI challenge. After scratching bouts and ear thickness were measured, cytokines were determined in challenged skin and the cells of the draining lymph node were analyzed by means of flow cytometry. In vitro, both JAK inhibitors significantly inhibited cytokine production, migration, and maturation of BMDCs. Mice treated orally with JAK inhibitors showed a significant decrease in scratching behavior; however, ear thickness was not significantly reduced. In contrast, both scratching behavior and ear thickness in the topical treatment group were significantly reduced compared with the vehicle treatment group. However, cytokine production was differentially regulated by the JAK inhibitors, with some cytokines being significantly decreased and some being significantly increased. In conclusion, oral treatment with JAK inhibitors reduced itch behavior dramatically but had only little effect on the inflammatory response, whereas topical treatment improved both itch and inflammatory response. Although the JAK-inhibitory profile differs between both JAK inhibitors in vitro as well as in vivo, the effects have been comparable. PMID- 26159874 TI - CYP2C19 Phenoconversion by Routinely Prescribed Proton Pump Inhibitors Omeprazole and Esomeprazole: Clinical Implications for Personalized Medicine. AB - The phenotype pantoprazole-(13)C breath test (Ptz-BT) was used to evaluate the extent of phenoconversion of CYP2C19 enzyme activity caused by commonly prescribed proton pump inhibitors (PPI) omeprazole and esomprazole. The Ptz-BT was administered to 26 healthy volunteers and 8 stable cardiovascular patients twice at baseline and after 28 days of PPI therapy to evaluate reproducibility of the Ptz-BT and changes in CYP2C19 enzyme activity (phenoconversion) after PPI therapy. The average intrapatient interday variability in CYP2C19 phenotype (n = 31) determined by Ptz-BT was considerably low (coefficient of variation, 17%). Phenotype conversion resulted in 25 of 26 (96%) nonpoor metabolizer (non-PM) volunteers/patients as measured by the Ptz-BT at baseline and after PPI therapy. The incidence of PM status by phenotype following administration of omeprazole/esomeprazole (known inhibitors of CYP2C19) was 10-fold higher than those who are genetically PMs in the general population, which could have critical clinical implications for personalizing medications primarily metabolized by CYP2C19, such as clopidogrel, PPI, cyclophosphamide, thalidomide, citalopram, clonazepam, diazepam, phenytoin, etc. The Ptz-BT can rapidly (30 minutes) evaluate CYP2C19 phenotype and, more importantly, can identify patients with phenoconversion in CYP2C19 enzyme activity caused by nongenetic factors such as concomitant drugs. PMID- 26159876 TI - Complete genome sequence and construction of infectious full-length cDNA clones of tobacco ringspot Nepovirus, a viral pathogen causing bud blight in soybean. AB - Tobacco ringspot virus (TRSV, genus Nepovirus), causes severe diseases in soybean and tobacco plants. TRSV-induced bud blight disease significantly reduced both the yield and quality of soybeans. The function of the encoded viral gene product involved in TRSV infection was unclear due to the limitation of reverse genetics studies on the viral genome. Here, we represent the successful construction of infectious full-length cDNA clones of TRSV genome (RNA1 and RNA2). The cDNAs of TRSV RNA1 and RNA2 were cloned into the binary vector pPZP211 immediately downstream of a double cauliflower mosaic virus 35S promoter and upstream of the nopaline synthase terminator. Seven days after agrobacterium-mediated co inoculation of these two constructs, Nicotiana benthamiana plants developed a systemic infection with necrotic ringspot symptoms and weak stunting of the leaves, similar to that induced by natural TRSV. The systemic infection was confirmed by transmission electron microscopy and Western blot analysis. Simultaneously, soybean, tomato, and Arabidopsis ecotype Estland were mechanically inoculated with sap prepared from TRSV-agroinfiltrated N. benthamiana leaves, showing typical symptoms of bud blight, necrotic spots, and lethal systemic necrosis, respectively. The system developed herein will be an appealing way to determine TRSV viral gene functions and study host-TRSV interactions. PMID- 26159875 TI - Pregnane X Receptor-Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity. AB - Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXR-humanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor alpha, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females. PMID- 26159877 TI - Detergent-, solvent- and salt-compatible thermoactive alkaline serine protease from halotolerant alkaliphilic Bacillus sp. NPST-AK15: purification and characterization. AB - Alkaline protease produced by the halotolerant alkaliphilic Bacillus sp. strain NPST-AK15 was purified to homogeneity by the combination of ammonium sulfate precipitation, anion-exchange and gel permeation chromatography. The purified enzyme was a monomeric protein with an estimated molecular weight of 32 kDa. NPST AK15 protease was highly active and stable over a wide pH range, with a maximal activity at pH 10.5. The enzyme showed optimum activity at 60 degrees C and was stable at 30-50 degrees C for at least 1 h. Thermal stability of the purified protease was substantially improved by CaCl2 (1.1- to 6.6-fold). The K m, V max and k cat values for the enzyme were 2.5 mg ml(-1), 42.5 uM min(-1) mg(-1), and 392.46 * 10(3) min(-1), respectively. NPST-AK15 protease activity was strongly inhibited by PMSF, suggesting that the enzyme is a serine protease. The enzyme was highly stable in NaCl up to 20 % (w/v). Moreover, the purified enzyme was stable in several organic solvents such as diethyl ether, benzene, toluene, and chloroform. In addition, it showed high stability and compatibility with a wide range of surfactants and commercial detergents and was slightly activated by hydrogen peroxide. These features of NPST-AK15 protease make this enzyme a promising candidate for application in the laundry and pharmaceutical industries. PMID- 26159878 TI - Disulfide-bridged peptide macrobicycles from nature. AB - Disulfide-bridged peptide bicycles (DBPBs) are molecules that contain a transannular disulfide bridge within a macrocyclic framework. While DBPBs are precedented in nature, the development of synthetic analogues and their use as therapeutic agents has yet to realize their full potential. A series of naturally occurring DBPBs and their respective structural and biological features is presented, followed by a description of synthetic methods used to prepare and understand these unique bicyclic systems. The synergy of high-throughput biology and synthetic chemistry should facilitate the development of novel DBPBs in the near future. PMID- 26159879 TI - Mercury Accumulation in Harbour Seals from the Northeastern Pacific Ocean: The Role of Transplacental Transfer, Lactation, Age and Location. AB - Mercury (Hg) bioaccumulates in the aquatic food chain in the form of methylmercury, a compound well known for its neurotoxicity. We analyzed total mercury (THg) in hair collected from 209 harbour seals captured at 10 sites in British Columbia (Canada) and Washington State (USA) between 2003 and 2010. In addition, laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) allowed for a highly refined analysis of THg accumulation over time by examining nine whiskers taken from 4- to 6-week-old pups. We estimate that THg concentrations in pups increased sharply at a point corresponding to mid- to late gestation of their time in utero (4.7 +/- 0.8 and 6.6 +/- 1.3 ug/g dry weight (dw), respectively), and then again at the onset of nursing (8.1 +/- 1.3 ug/g dw). These abrupt changes highlight the importance of both pre- and post-natal THg transfer from the mother to the growing fetus and the newborn pup. While THg levels varied among sites, hair analyses from seals collected at the same site demonstrated the influence of age in THg accumulation with pups (5.3 +/- 0.3 ug/g) and juveniles (4.5 +/- 0.5 ug/g) having lower levels than those in adults (8.3 +/- 0.8 ug/g). Our results revealed that 33 % of the pups sampled (n = 167) had THg levels that surpassed a mammalian hair threshold for neurochemical alterations. This study suggests that Hg could represent a health concern to marine wildlife, especially as atmospheric emissions of this toxic element from human activities in the Pacific Rim and worldwide continue. PMID- 26159880 TI - Calhex231 Ameliorates Cardiac Hypertrophy by Inhibiting Cellular Autophagy in Vivo and in Vitro. AB - BACKGROUND/AIMS: Intracellular calcium concentration ([Ca2+]i) homeostasis, an initial factor of cardiac hypertrophy, is regulated by the calcium-sensing receptor (CaSR) and is associated with the formation of autolysosomes. The aim of this study was to investigate the role of Calhex231, a CaSR inhibitor, on the hypertrophic response via autophagy modulation. METHODS: Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in 40 male Wistar rats, while 10 rats underwent a sham operation and served as controls. Cardiac function was monitored by transthoracic echocardiography, and the hypertrophy index was calculated. Cardiac tissue was stained with hematoxylin and eosin (H&E) or Masson's trichrome reagent and examined by transmission electron microscopy. An angiotensin II (Ang II)-induced cardiomyocyte hypertrophy model was established and used to test the involvement of active molecules. Intracellular calcium concentration ([Ca2+]i) was determined by the introduction of Fluo-4/AM dye followed by confocal microscopy. The expression of various active proteins was analyzed by western blot. RESULTS: The rats with TAC-induced hypertrophy had an increased heart size, ratio of heart weight to body weight, myocardial fibrosis, and CaSR and autophagy levels, which were suppressed by Calhex231. Experimental results using Ang II-induced hypertrophic cardiomyocytes confirmed that Calhex231 suppressed CaSR expression and downregulated autophagy by inhibiting the Ca2+/calmodulin-dependent-protein kinase-kinase-beta (CaMKKbeta)- AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway to ameliorate cardiomyocyte hypertrophy. CONCLUSIONS: Calhex231 ameliorates myocardial hypertrophy induced by pressure-overload or Ang II via inhibiting CaSR expression and autophagy. Our results may support the notion that Calhex231 can become a new therapeutic agent for the treatment of cardiac hypertrophy. PMID- 26159881 TI - Future Directions in the Study of Personality in Adulthood and Older Age. AB - Over the past 20 years, empirical evidence has brought about a change in the view on how, or even whether, personality traits change or develop in adulthood and later life. Now we know personality can and does change for many people, if not most. Changes in personality may occur due to biological or environmental factors. This paper presents key empirical findings on personality change in adulthood and provides evidence that personality change affects mental and physical health. Our goal is to provide a broad overview on personality change research that would be an invaluable resource for students and researchers. We organize this paper into 3 sections. The first is focused on techniques in analyzing personality change in adulthood and later life. The second is focused on personality change as an outcome; we explore what factors predict personality change. The third discusses a relatively novel idea: personality change as a predictor of mental and physical health. We conclude that more research on factors predicting personality change is needed and we provide suggestions on how research on personality change can progress. PMID- 26159882 TI - Utility of the Standardized Assessment of Concussion (SAC) to Detect Insufficient Effort in Independent Medical Examinations and Civil Litigation Cases. AB - OBJECTIVE: The Standardized Assessment of Concussion (SAC) is a standardized mental status screening instrument initially developed for assessment and tracking of concussion symptoms in athletes. The purpose of the current study was to validate the utility of the SAC as an embedded screening measure for insufficient effort in independent medical examinations (IME) and personal injury cases. METHOD: A known-groups design was used to examine the SAC's utility for the detection of insufficient effort in 75 de-identified private IME and civil litigation evaluations. Initial classifications of insufficient effort were made independently of SAC scores, on the basis of having two or more scores falling below established cut-offs on previously validated neuropsychological measures. RESULTS: Results suggest that the total score on the SAC significantly distinguishes effortful respondents from those exhibiting insufficient effort. Empirically derived cut-off scores yielded adequate sensitivity (.62-.95) and negative predictive power (.93-.97). CONCLUSIONS: While optimal cut-off scores depend upon intended use, our data suggest that the SAC is useful as a potential screener for insufficient effort, after which one can employ additional measures to rule out false-positives. Further research is required before cut-off scores can be recommended for clinical use. PMID- 26159883 TI - Social dimensions of inclusion in education of 4th and 7th grade pupils in inclusive and regular classes: Outcomes from Austria. AB - Positive peer relationships play a significant role in the development of students. They are beneficial for learning and psychological outcomes. This article draws upon an important distinction between the four main themes of social participation (friendships, interactions, peer acceptance and self perception of social participation) and examines these aspects in inclusive and regular classes. Especially, differences in social participation of students with and without special educational needs (SEN) in inclusive classes and between students without SEN in inclusive and regular classes are examined. In this study, data from 1115 pupils in primary and secondary schools in Austria were analysed, of which 129 were diagnosed as having SEN. The results showed that in inclusive classes, students with SEN had lower scores on all four subthemes of social participation (friendships, interactions, peer acceptance and self perception of social integration) than students without SEN. Regarding students without SEN, friendships and peer acceptance were significantly higher in inclusive classes than in regular classes. Differences were neither found for gender, nor between primary and secondary school students. PMID- 26159885 TI - Field and dilution effects on the magnetic relaxation behaviours of a 1D dysprosium(iii)-carboxylate chain built from chiral ligands. AB - A one-dimensional dysprosium(iii)-carboxylate chain in which the Dy(III) ions sit in a pseudo D(2d)-symmetry environment is synthesized and shows different slow magnetic relaxation behaviours depending on the field and dilution effects. Besides, the chiral ligand introduces the additional functions of the Cotton effect and polarization for this compound. PMID- 26159884 TI - Comparing social reciprocity in preserved speech variant and typical Rett syndrome during the early years of life. AB - This study compared early markers of social reciprocity in children with typical Rett syndrome (RTT) and in those with the preserved speech variant (PSV) of RTT. Retrospective video analysis of 10 toddlers with typical RTT and five with PSV investigated participants' orientation to their name being called between the ages of 5 and 24 months, prior to their diagnosis. From analysis of the recordings two distinct profiles were apparent. Although response rate was higher in girls with typical RTT than PSV at 5 to 8 months this noticeably reversed from 9 to 12 months onwards. By two years of age there was a markedly higher rate and range of responses from girls with PSV. This study contributes to the delineation of different profiles for the variants of RTT. PMID- 26159886 TI - Surviving the Distance: The Transnational Utilization of Traditional Medicine Among Oaxacan Migrants in the US. AB - Transnational health practices are an emergent and understudied phenomenon, which provide insight into how migrants seek care and tend to their health care needs in receiving communities. We conducted in depth interviews with return migrants (N = 21) and traditional healers (N = 11) to explore transnational health practices among Mixtec migrants from Oaxaca, specifically in relation to their utilization of traditional healers, medicinal plants, and folk remedies. In established migrant destination points, folk remedies and plants are readily available, and furthermore, these resources often travel alongside migrants. Traditional healers are integral to transnational networks, whether they migrate and provide services in the destination point, or are providing services from communities of origin. Findings encourage us to rethink migrants' communities of origin typically thought of as "left behind," and instead reposition them as inherently connected by transnational channels. Implications for transnational health care theory and practice are addressed. PMID- 26159887 TI - ROS1 rearranged non-small cell lung cancer brain metastases respond to low dose radiotherapy. AB - We present a young woman with ROS1 gene rearranged non-small cell lung cancer (NSCLC) with brain metastases. ROS is a proto-oncogene tyrosine protein kinase. The patient received a partial course of whole brain radiation therapy and experienced a sustained partial response in the brain. We hypothesize that ROS1 rearranged NSCLC brain metastases may be particularly sensitive to radiation therapy. PMID- 26159889 TI - Age Does Matter: A Pilot Comparison of Placenta-Derived Stromal Cells for in utero Repair of Myelomeningocele Using a Lamb Model. AB - INTRODUCTION: Fetal amniotic membranes (FM) have been shown to preserve spinal cord histology in the fetal sheep model of myelomeningocele (MMC). This study compares the effectiveness of placenta-derived mesenchymal stromal cells (PMSCs) from early-gestation versus term-gestation placenta to augment FM repair to improve distal motor function in a sheep model. METHODS: Fetal lambs (n = 4) underwent surgical MMC creation followed by repair with FM patch with term gestation PMSCs (n = 1), FM with early-gestation PMSCs (n = 1), FM only (n = 1), and skin closure only (n = 1). Histopathology and motor assessment was performed. RESULTS: Histopathologic analysis demonstrated increased preservation of spinal cord architecture and large neurons in the lamb repaired with early-gestation cells compared to all others. Lambs repaired with skin closure only, FM alone, and term-gestation PMSCs exhibited extremely limited distal motor function; the lamb repaired with early-gestation PMSCs was capable of normal ambulation. DISCUSSION: This pilot study is the first in vivo comparison of different gestational-age placenta-derived stromal cells for repair in the fetal sheep MMC model. The preservation of large neurons and markedly improved motor function in the lamb repaired with early-gestation cells suggest that early-gestation placental stromal cells may exhibit unique properties that augment in utero MMC repair to improve paralysis. PMID- 26159890 TI - Bayesian principal geodesic analysis for estimating intrinsic diffeomorphic image variability. AB - In this paper, we present a generative Bayesian approach for estimating the low dimensional latent space of diffeomorphic shape variability in a population of images. We develop a latent variable model for principal geodesic analysis (PGA) that provides a probabilistic framework for factor analysis in the space of diffeomorphisms. A sparsity prior in the model results in automatic selection of the number of relevant dimensions by driving unnecessary principal geodesics to zero. To infer model parameters, including the image atlas, principal geodesic deformations, and the effective dimensionality, we introduce an expectation maximization (EM) algorithm. We evaluate our proposed model on 2D synthetic data and the 3D OASIS brain database of magnetic resonance images, and show that the automatically selected latent dimensions from our model are able to reconstruct unobserved testing images with lower error than both linear principal component analysis (LPCA) in the image space and tangent space principal component analysis (TPCA) in the diffeomorphism space. PMID- 26159892 TI - X-ray diffraction from bone employing annular and semi-annular beams. AB - There is a compelling need for accurate, low cost diagnostics to identify osteo tissues that are associated with a high risk of fracture within an individual. To satisfy this requirement the quantification of bone characteristics such as 'bone quality' need to exceed that provided currently by densitometry. Bone mineral chemistry and microstructure can be determined from coherent x-ray scatter signatures of bone specimens. Therefore, if these signatures can be measured, in vivo, to an appropriate accuracy it should be possible by extending terms within a fracture risk model to improve fracture risk prediction.In this preliminary study we present an examination of a new x-ray diffraction technique that employs hollow annular and semi-annular beams to measure aspects of 'bone quality'. We present diffractograms obtained with our approach from ex vivo bone specimens at Mo Kalpha and W Kalpha energies. Primary data is parameterized to provide estimates of bone characteristics and to indicate the precision with which these can be determined. PMID- 26159891 TI - Black-white racial disparities in sepsis: a prospective analysis of the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. AB - INTRODUCTION: Sepsis is a major public health problem. Prior studies using hospital-based data describe higher rates of sepsis among black than whites participants. We sought to characterize racial differences in incident sepsis in a large cohort of adult community-dwelling adults. METHODS: We analyzed data on 29,690 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We determined the associations between race and first infection and first-sepsis events, adjusted for participant sociodemographics, health behaviors, chronic medical conditions and biomarkers. We also determined the association between race and first-sepsis events limited to first-infection events. We contrasted participant characteristics and hospital course between black and white sepsis hospitalizations. RESULTS: Among eligible REGARDS participants there were 12,216 (41.1%) black and 17,474 (58.9%) white participants. There were 2,600 first-infection events; the incidence of first infection events was lower for black participants than for white participants (12.10 vs. 15.76 per 1,000 person-years; adjusted HR 0.65; 95% CI, 0.59-0.71). There were 1,526 first-sepsis events; the incidence of first-sepsis events was lower for black participants than for white participants (6.93 vs. 9.10 per 1,000 person-years, adjusted HR 0.64; 95% CI, 0.57-0.72). When limited to first infection events, the odds of sepsis were similar between black and white participants (adjusted OR 1.01; 95% CI, 0.84-1.21). Among first-sepsis events, black participants were more likely to be diagnosed with severe sepsis (76.9% vs. 71.5%). CONCLUSION: In the REGARDS cohort, black participants were less likely than white participants to experience infection and sepsis events. Further efforts should focus on elucidating the underlying reasons for these observations, which are in contrast to existing literature. PMID- 26159893 TI - Global Individual Ancestry Using Principal Components for Family Data. AB - Studies of complex human diseases and traits associated with candidate genes are potentially vulnerable to bias (confounding) due to population stratification and inbreeding, especially in admixed population. In GWAS, the principal components (PCs) method provides a global ancestry value per subject, allowing corrections for population stratification. However, these coefficients are typically estimated assuming unrelated individuals, and if family structure is present and ignored, such substructures may induce artifactual PCs. Extensions of the PCs method have been proposed by Konishi and Rao [Biometrika 1992;79:631-641], taking into account only siblings' relatedness, and by Oualkacha et al. [Stat Appl Genet Mol Biol 2012, DOI: 10.2202/1544-6115.1711], taking into account large pedigrees and high-dimensional phenotype data. In this work, we extend these methods to estimate the global individual ancestry coefficients from PCs derived from different variance component matrix estimators using SNPs from two simulated data sets and two real data sets: the GENOA sibship data consisting of European and African-American subjects and the Baependi Heart Study consisting of 80 extended Brazilian families, both with genotyping data from the Affymetrix 6.0 chip. Our results show that the family structure plays an important role in the estimation of the global individual ancestry value for extended pedigrees but not for sibships. PMID- 26159894 TI - Retrospective Assessment of the Utility of Imaging, Fine-Needle Aspiration Biopsy, and Intraoperative Frozen Section in the Management of Parotid Neoplasms: The Weill Cornell Medical College Experience. AB - BACKGROUND/AIMS: Preoperative identification of malignant parotid lesions remains challenging, and thus, some surgeons use frozen section (FS) to assist them in their decision making. We evaluated the pathologic and cost benefit of FS after fine-needle aspiration (FNA) at our institution. METHODS: We assessed medical data for 260 patients undergoing parotidectomy with FS. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for radiology, FNA, and FS. RESULTS: The sensitivities, specificities, and accuracies of FNA and FS were 75.0, 96.4, and 93.2%, and 75.0, 100, and 96.8%, respectively. FS detected 0% of FNA false negatives and 80% of false positives. The additional pathology charge for FS alone per correctly identified benign lesion after a positive FNA was USD 1,443. CONCLUSION: FNA and FS are more reliable in the prognostication of the final pathology than radiology. At our center, FS appears to be of limited clinical use after benign FNAs, but may be more useful after positive, indeterminate, and nondiagnostic FNAs. PMID- 26159895 TI - l-Histidyl-glycyl-glycyl-l-histidine. Amino-acid structuring of the bleomycin type pentadentate metal-binding environment capable of efficient double-strand cleavage of plasmid DNA. AB - A tetrapeptide, l-histidyl-glycyl-glycyl-l-histidine (HGGH), was synthesized and the pUC19 plasmid DNA cleaving activity by copper(II) complex of HGGH (Cu(II) HGGH) was investigated. Cu(II)-HGGH showed bleomycin-like DNA cleaving activity and, at 50nM, converted a supercoiled DNA efficiently to a linear DNA in the presence of 500MUM H2O2/sodium ascorbate through an oxidative pathway. PMID- 26159896 TI - Charge collection enhancement by incorporation of gold-silica core-shell nanoparticles into P3HT:PCBM/ZnO nanorod array hybrid solar cells. AB - In this work, gold-silica core-shell (Au@silica) nanoparticles (NPs) with various silica-shell thicknesses are incorporated into P3HT:PCBM/ZnO nanorod (NR) hybrid solar cells. Enhancement in the short-circuit current density and the efficiency of the hybrid solar cells is attained with the appropriate addition of Au@silica NPs regardless of the silica-shell thickness. Compared to the P3HT:PCBM/ZnO NR hybrid solar cell, a 63% enhancement in the efficiency is achieved by the P3HT:PCBM/Au@silica NP/ZnO NR hybrid solar cell. The finite difference time domain simulations indicate that the strength of the Fano resonance, i.e., the electric field of the quasi-static asymmetric quadrupole, on the surface of Au@silica NPs in the P3HT:PCBM/ZnO NR hybrid significantly decreases with increasing thickness of the silica shell. Raman characterization reveals that the degree of P3HT order increases when Au@silica NPs are incorporated into the P3HT:PCBM/ZnO NR hybrid. The charge separation at the interface between P3HT and PCBM as well as the electron transport in the active layer are retarded by the electric field of the Fano resonance. Nevertheless, the prolongation of the electron lifetime and the reduction of the electron transit time in the P3HT:PCBM/ZnO NR hybrid solar cells, which result in an enhancement of electron collection, are achieved by the addition of Au@silica NPs. This may be attributed to the improvement in the degree of P3HT order and connectivity of PCBM when Au@silica NPs are incorporated into the P3HT:PCBM active layer. PMID- 26159897 TI - Mucinous adenocarcinoma emerging in sigmoid colon neovagina 40 years after its creation: a case report. AB - BACKGROUND: We reported our experience of adenocarcinoma of sigmoid colon neovagina. CASE PRESENTATION: A 67-year-old female with a history of neovagina construction for Rokitansky syndrome complained of vaginal bleeding. She had a mucinous adenocarcinoma at the anterior aspect of the neovagina. Her original surgery, using sigmoid colon to construct the artificial vagina, was 40 years ago CONCLUSIONS: This patient's case may contribute to our understanding of carcinogenesis in the colon. PMID- 26159898 TI - Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer's disease. AB - AIM: Novel effective treatment is urgently needed for sporadic Alzheimer's disease (sAD). M30 ([5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]) and HLA-20 (5-{4-propargylpiperazin-1-ylmethyl}-8-hydroxyquinoline) are brain permeable, iron chelating compounds with antioxidant activity, showing also neuroprotective activity in animal models of neurodegeneration.Weaimed to explore their therapeutic potential in non-transgenic (non-Tg) rat model of sAD developed by intracerebroventricular administration of streptozotocin (STZ-icv). MAIN METHODS: Therapeutic effects of chronic oral M30 (2 and 10 mg/kg) and HLA20 (5 and 10 mg/kg) treatment on cognitive impairment in STZ-icv rat model were explored by Morris Water Maze (MWM) and Passive Avoidance (PA) tests in neuropreventive and neurorescue paradigms. Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p b 0.05). KEY FINDINGS: Five-day oral pre-treatment with M30 and HLA20 dose-dependently prevented development of spatial memory impairment (MWM probe trial-time +116%/M30; +60%/HLA20) in STZ-icv rat model (p b 0.05). Eleven-week oral treatment with M30 (3*/week), initiated 8 days after STZ icv administration dosedependently ameliorated already developed cognitive deficits in MWM test (reduced number of mistakes 3 months after the STZ-icv treatment - 59%; p b 0.05) and fully restored them in PA test (+314%; p b 0.05). Chronic M30 treatment fully restored (-47%/PHF1;-65%/AT8; p b 0.05) STZ-induced hyperphosphorylation of tau protein and normalized decreased expression of insulin degrading enzyme (+37%; p b 0.05) in hippocampus. SIGNIFICANCE: The results provide first evidence of therapeutic potential of M30 and HLA20 in STZ icv rat model of sAD with underlying molecular mechanism, further supporting the important role of multi-target ironchelators in sAD treatment. PMID- 26159899 TI - Cross-linking of sodium caseinate-structured emulsion with transglutaminase alters postprandial metabolic and appetite responses in healthy young individuals. AB - The physico-chemical and interfacial properties of fat emulsions influence lipid digestion and may affect postprandial responses. The aim of the present study was to determine the effects of the modification of the interfacial layer of a fat emulsion by cross-linking on postprandial metabolic and appetite responses. A total of fifteen healthy individuals (26.5 (sem 6.9) years and BMI 21.9 (sem 2.0) kg/m2) participated in a cross-over design experiment in which they consumed two isoenergetic (1924 kJ (460 kcal)) and isovolumic (250 g) emulsions stabilised with either sodium caseinate (Cas) or transglutaminase-cross-linked sodium caseinate (Cas-TG) in a randomised order. Blood samples were collected from the individuals at baseline and for 6 h postprandially for the determination of serum TAG and plasma NEFA, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose and insulin responses. Appetite was assessed using visual analogue scales. Postprandial TAG and NEFA responses and gastric emptying (GE) rates were comparable between the emulsions. CCK increased more after the ingestion of Cas TG than after the ingestion of Cas (P< 0.05), while GLP-1 responses did not differ between the two test emulsions. Glucose and insulin profiles were lower after consuming Cas-TG than after consuming Cas (P< 0.05). The overall insulin, glucose and CCK responses, expressed as areas above/under the curve, did not differ significantly between the Cas and Cas-TG meal conditions. Satiety ratings were reduced and hunger, desire to eat and thirst ratings increased more after the ingestion of Cas-TG than after the ingestion of Cas (P< 0.05). The present results suggest that even a subtle structural modification of the interfacial layer of a fat emulsion can alter the early postprandial profiles of glucose, insulin, CCK, appetite and satiety through decreased protein digestion without affecting significantly on GE or overall lipid digestion. PMID- 26159900 TI - Yin Yang 1 is a multi-functional regulator of adipocyte differentiation in 3T3-L1 cells. AB - Yin Yang 1 (YY1) is an ubiquitously distributed transcription factor that belongs to the GLI-Kruppel class of zinc finger proteins. The mechanism by which YY1 regulates adipocyte differentiation remains unclear. In this study, we investigated the functional role of YY1 during adipocyte differentiation. During the early stage, YY1 gene and protein expression was transiently downregulated upon the induction of differentiation, however, it was consistently induced during the later stage. YY1 overexpression decreased adipocyte differentiation and blocked cell differentiation at the preadipocyte stage, while YY1 knockdown by RNA interference increased adipocyte differentiation. YY1 physically interacted with PPARgamma (Peroxisome proliferator-activated receptor gamma) and C/EBPbeta (CCAAT/enhancer-binding protein beta) respectively in 3T3-L1 cells. Through its interaction with PPARgamma, YY1 directly decreased PPARgamma transcriptional activity. YY1 ectopic expression prevented C/EBPbeta from binding to the PPARgamma promoter, resulting in the downregulation of PPARgamma transcriptional activity. These results indicate that YY1 repressed adipocyte differentiation by repressing the activity of adipogenic transcriptional factors in 3T3-L1 cells. PMID- 26159901 TI - YC-1 reduces placental sFlt-1 and soluble endoglin production and decreases endothelial dysfunction: A possible therapeutic for preeclampsia. AB - Preeclampsia is a serious complication of pregnancy with no medical treatment. It is caused by intermittent placental hypoxia and release of sFlt-1 and soluble endoglin, leading to wide spread maternal endothelial dysfunction and multisystem organ injury. YC-1 is a guanylyl cyclase activator and HIF1alpha inhibitor developed for use in hypertension and atherosclerosis. We examined whether YC-1 reduces sFlt-1 and sENG secretion and reverses endothelial dysfunction in primary human tissues. YC-1 significantly reduced sFlt-1 and sENG secretion from human umbilical vein endothelial cells, purified primary trophoblast cells and placental explants taken from patients with preterm preeclampsia. This was concordant with reduced HIF1alpha expression. YC-1 also reversed TNFalpha induced endothelial dysfunction, including reduced vascular cell adhesion molecule 1 expression and monocyte adhesion to primary endothelial cells. We conclude YC-1 decreases placental production of sFlt-1 and sENG and decreases endothelial dysfunction. It is a novel therapeutic candidate for preeclampsia. PMID- 26159902 TI - DNA Repair Gene Polymorphisms in Relation to Non-Small Cell Lung Cancer Survival. AB - BACKGROUND: Single nucleotide polymorphisms (SNPs) in the DNA repair genes are suspected to be related to the survival of lung cancer patients due to their possible influence on DNA repair capacity (DRC). However, the study results are inconsistent. METHODS: A follow-up study of 610 non-small cell lung cancer (NSCLC) patients was conducted to investigate genetic polymorphisms associated with the DNA repair genes in relation to NSCLC survival; 6 SNPs were genotyped, including XRCC1 (rs25487 G>A), hOGG1 (rs1052133 C>G), MUTYH (rs3219489 G>C), XPA (rs1800975 G>A), ERCC2 (rs1799793 G>A) and XRCC3 (rs861539 C>T). Kaplan- Meier survival curve and Cox proportional hazards regression analyses were performed. SNP-SNP interaction was also examined using the survival tree analysis. RESULTS: Advanced disease stage and older age at diagnosis were associated with poor prognosis of NSCLC. Patients with the variant 'G' allele of hOGG1 rs1052133 had poor overall survival compared with those with the homozygous wild 'CC' genotype, especially in female patients, adenocarcinoma histology, early stage, light smokers and without family history of cancer. For never smoking female lung cancer patients, individuals carrying homozygous variant 'AA' genotype of XPA had shorter survival time compared to those with wild 'G' alleles. Furthermore, females carrying homozygous variant XPA and hOGG1 genotypes simultaneously had 2.78-fold increased risk for death. Among all 6 polymorphisms, the homozygous variant 'AA' of XPA carriers had poor prognosis compared to the carriers of wild 'G' alleles of XPA together with other base excision repair (BER) polymorphisms. CONCLUSIONS: Besides disease stage and age, the study found DNA repair gene polymorphisms were associated with lung cancer survival. PMID- 26159903 TI - Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations. AB - An increased prevalence of cystic fibrosis (CF) related complications such as impaired bone health and diabetes has accompanied increased survival of patients with CF. This review was conducted to determine the extent to which adults with CF are meeting current nutrition recommendations for micronutrients in association with CF-related complications management. Although dietary intake and nutritional status in CF has improved significantly in recent decades, micronutrient status seems to have diverged. While vitamin A and E intakes appear adequate, frequent vitamin D and K deficiency/insufficiency and compromised bone health in CF, occurs despite supplementation. Although deficiency of water soluble vitamins and minerals is uncommon, ongoing surveillance will enhance overall health outcomes, particularly in cases of CF-related liver disease and deteriorated lung function and bone health. Salt and fluid status in CF may also need attention due to diminished thirst sensation and voluntary rehydration. Further investigation in micronutrient status optimisation in CF will inform the development of more effective and targeted nutrition therapies to enable integration of more refined recommendations for micronutrient intakes in CF based on individual needs and disease progression. PMID- 26159904 TI - Environmental Hyperthermia in Prehospital Patients with Major Traumatic Brain Injury. AB - BACKGROUND: Traumatic brain injury (TBI) results in an estimated 1.7 million emergency department visits each year in the United States. These injuries frequently occur outside, leaving injured individuals exposed to environmental temperature extremes before they are transported to a hospital. OBJECTIVE: Evaluate the existing literature for evidence that exposure to high temperatures immediately after TBI could result in elevated body temperatures (EBTs), and whether or not EBTs affect patient outcomes. DISCUSSION: It has been clear since the early 1980s that after brain injury, exposure to environmental temperatures can cause hypothermia, and that this represents a significant contributor to increased morbidity and mortality. Less is known about elevated body temperature. Early evidence from the Iraq and Afghanistan wars indicated that exposure to elevated environmental temperatures in the prehospital setting may result in significant EBTs, however, it is unclear what impact these EBTs might have on outcomes in TBI patients. In the hospital, EBT, or neurogenic fever, is thought to be due to the acute-phase reaction that follows critical injury, and these high body temperatures are associated with poor outcomes after TBI. CONCLUSION: Hospital data suggest that EBTs are associated with poor outcomes, and some preliminary reports suggest that early EBTs are common after TBI in the prehospital setting. However, it remains unclear whether patients with TBI have an increased risk of EBTs after exposure to high environmental temperatures, or if this very early "hyperthermia" might cause secondary injury after TBI. PMID- 26159905 TI - Acute Porphyrias. AB - BACKGROUND: Porphyrias are a group of eight metabolic disorders characterized by defects in heme biosynthesis. Porphyrias are classified into two major categories: 1) the acute or inducible porphyrias and 2) the chronic cutaneous porphyrias. The acute hepatic porphyrias are further classified into acute intermittent porphyria (AIP), hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of delta-aminolevulinic acid (ALA) dehydratase (ALADP). DISCUSSION: AIP is the most common, and ALADP is the least common acute porphyria. The clinical presentations of acute porphyrias are nonspecific. There are no pathognomonic signs or symptoms. The most frequent presenting symptom is abdominal pain, but pain in the chest, back, or lower extremities may also occur. Hyponatremia is the most common electrolyte abnormality during acute attacks, and hypomagnesemia is also common. Both are risk factors for development of seizures, which occur in ~ 20-30% of acute attacks. CONCLUSION: Once suspected, the diagnosis of porphyria can be rapidly established by checking random urinary porphobilinogen. Initial management of acute porphyria includes discontinuation of all potentially harmful drugs and management of symptoms. Acute attacks should be treated emergently with intravenous heme and glucose to avoid considerable morbidity and mortality. Acute attacks last a few days, and the majority of patients are asymptomatic between attacks. Prognosis is good if the condition is recognized early and treated aggressively. PMID- 26159906 TI - Quantitative breast mass classification based on the integration of B-mode features and strain features in elastography. AB - BACKGROUND: Elastography is a new sonographic imaging technique to acquire the strain information of tissues and transform the information into images. Radiologists have to observe the gray-scale distribution of tissues on the elastographic image interpreted as the reciprocal of Young's modulus to evaluate the pathological changes such as scirrhous carcinoma. In this study, a computer aided diagnosis (CAD) system was developed to extract quantitative strain features from elastographic images to reduce operator-dependence and provide an automatic procedure for breast mass classification. METHOD: The collected image database was composed of 45 malignant and 45 benign breast masses. For each case, tumor segmentation was performed on the B-mode image to obtain tumor contour which was then mapped to the elastographic images to define the corresponding tumor area. The gray-scale pixels around tumor area were classified into white, gray, and black by fuzzy c-means clustering to highlight stiff tissues with darker values. Quantitative strain features were then extracted from the black cluster and compared with the B-mode features in the classification of breast masses. RESULTS: The performance of the proposed strain features achieved an accuracy of 80% (72/90), a sensitivity of 80% (36/45), a specificity of 80% (36/45), and a normalized area under the receiver operating characteristic curve, Az=0.84. Combining the strain features with the B-mode features obtained a significantly better Az=0.93, p-value<0.05. CONCLUSIONS: Summarily, the quantified strain features can be combined with the B-mode features to provide a promising suggestion in distinguishing malignant from benign tumors. PMID- 26159907 TI - Towards a comprehensive phylogeny of the large temperate genus Pedicularis (Orobanchaceae), with an emphasis on species from the Himalaya-Hengduan Mountains. AB - BACKGROUND: Striking interspecific variations in floral traits of the large temperate genus Pedicularis have given rise to controversies concerning infra generic classifications. To date, phylogenetic relationships within the genus have not been well resolved. The main goal of this study is to construct a backbone phylogeny of Pedicularis, with extensive sampling of species from the Himalaya-Hengduan Mountains. Phylogenetic analyses included 257 species, representing all 13 informal groups and 104 out of 130 series in the classification system of Tsoong, using sequences of the nuclear ribosomal internal transcribed spacer (nrITS) and three plastid regions (matK, rbcL and trnL-F). Bayesian inference and maximum likelihood methods were applied in separate and combined analyses of these datasets. RESULTS: Thirteen major clades are resolved with strong support, although the backbone of the tree is poorly resolved. There is little consensus between the phylogenetic tree and Tsoong's classification of Pedicularis. Only two of the 13 groups (15.4 %), and 19 of the 56 series (33.9 %) with more than one sampled species were found to be strictly monophyletic. Most opposite-/whorled-leaved species fall into a single clade, i.e. clade 1, while alternate leaves species occur in the remaining 12 clades. Excluding the widespread P. verticillata in clade 1, species from Europe and North America fall into clades 6-8. CONCLUSIONS: Our results suggest that combinations of morphological and geographic characters associated with strongly supported clades are needed to elucidate a comprehensive global phylogeny of Pedicularis. Alternate leaves are inferred to be plesiomorphic in Pedicularis, with multiple transitions to opposite/whorled phyllotaxy. Alternate-leaved species show high diversity in plant habit and floral forms. In the Himalaya Hengduan Mountains, geographical barriers may have facilitated diversification of species with long corolla tubes, and the reproductive advantages of beakless galeas in opposite-/whorled-leaved species may boost speciation at high altitude. PMID- 26159908 TI - Has evidence-based psychosocial treatment for anxiety disorders permeated usual care in community mental health settings? AB - Cognitive behavioral therapy (CBT), particularly when it includes an exposure component, is an empirically supported psychosocial treatment for anxiety disorders that has been shown to be highly efficacious, desirable to patients, and cost-effective. However, access to and receipt of exposure-based treatment CBT anxiety remains lacking despite these benefits. The current study reviewed electronic medical records at a large public outpatient psychiatry clinic in order to clarify what usual care for anxiety disorders entails, and to determine the extent to which effective psychosocial treatment is accessible to, and implemented with anxiety disorder patients. Database queries generated from the billing and medical record system at the Los Angeles County Adult Outpatient Psychiatry Clinic identified 582 patients presenting with an anxiety disorder diagnosis in a 6-month time frame. These patients' electronic medical records were reviewed using a standardized data collection form. Findings indicated that the majority of patients received pharmacological treatment for their anxiety. The majority of the psychosocial treatment delivered was supportive therapy. Among the minority of patients who did initiate CBT, an even smaller minority received treatment that included an exposure component, and those who did receive exposure likely received a sub-optimal dose. Understanding usual care delivery patterns is an important preliminary step to identifying and addressing barriers to optimal anxiety disorder treatment in adult community mental health settings. PMID- 26159909 TI - Blocking primers reduce co-amplification of plant DNA when studying bacterial endophyte communities. AB - A blocking primer set based on the technique described by Vestheim and Jarman (2008) was developed to reduce amplification of non-target plant DNA when conducting metagenomic studies on bacterial endophyte communities. Bacterial amplification efficiency was increased 300-fold compared to standard PCR in an Illumina-based study of Sorghastrum nutans leaves. PMID- 26159910 TI - Evaluation of a novel immunochromatographic device for rapid and accurate clinical detection of Porphyromonas gingivalis in subgingival plaque. AB - An important goal for the improved diagnosis and management of infectious and inflammatory diseases, such as periodontitis, is the development of rapid and accurate technologies for the decentralized detection of bacterial pathogens. The aim of this prospective multicenter study was to evaluate the clinical use of a novel immunochromatographic device with monoclonal antibodies for the rapid point of-care detection and semi-quantification of Porphyromonas gingivalis in subgingival plaque. Sixty-three patients with chronic periodontitis and 28 periodontally healthy volunteers were subjected to clinical and microbiological examinations. Subgingival plaque samples were analyzed for the presence of P. gingivalis using a novel immunochromatography based device DK13-PG-001, designed to detect the 40k-outer membrane protein of P. gingivalis, and compared with a PCR-Invader method. In the periodontitis group, a significant strong positive correlation in detection results was found between the test device score and the PCR-Invader method (Spearman rank correlation, r=0.737, p<0.0001). The sensitivity, specificity, and positive and negative predictive values of the test device were 96.2%, 91.8%, 90.4% and 96.7%, respectively. The detection threshold of the test device was determined to be approximately 10(4) (per two paper points). There were significant differences in the bacterial counts by the PCR Invader method among groups with different ranges of device scores. With a cut off value of >=0.25 in device score, none of periodontally healthy volunteers were tested positive for the subgingival presence of P. gingivalis, whereas 76% (n=48) of periodontitis subjects were tested positive. There was a significant positive correlation between device scores for P. gingivalis and periodontal parameters including probing pocket depth and clinical attachment level (r=0.317 and 0.281, respectively, p<0.01). The results suggested that the DK13-PG-001 device kit can be effectively used for rapid, chair-side detection and semi quantification of P. gingivalis in subgingival plaque. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000011943. PMID- 26159911 TI - Spatiotemporal variation in diabetes mortality in China: multilevel evidence from 2006 and 2012. AB - BACKGROUND: Despite previous studies reporting spatial in equality in diabetes prevalence across China, potential geographic variations in diabetes mortality have not been explored. METHODS: Age and gender stratified annual diabetes mortality counts for 161 counties were extracted from the China Mortality Surveillance System and interrogated using multilevel negative binomial regression. Random slopes were used to investigate spatiotemporal variation and the proportion of variance explained was used to assess the relative importance of geographical region, urbanization, mean temperature, local diabetes prevalence, behavioral risk factors and relevant biomarkers. RESULTS: Diabetes mortality tended to reduce between 2006 and 2012, though there appeared to be an increase in diabetes mortality in urban (age standardized rate (ASR) 2006-2012: 10.5-13.6) and rural (ASR 10.8-13.0) areas in the Southwest region. A Median Rate Ratio of 1.47, slope variance of 0.006 (SE 0.001) and covariance of 0.268 (SE 0.007) indicated spatiotemporal variation. Fully adjusted models accounted for 37% of this geographical variation, with diabetes mortality higher in the Northwest (RR 2.55, 95% CI 1.74, 3.73) and Northeast (RR 2.68, 95% CI 1.70, 4.21) compared with the South. Diabetes mortality was higher in urbanized areas (RR tertile 3 versus tertile 1 ('RRt3vs1') 1.39, 95% CI 1.17, 1.66), with higher mean body mass index (RRt3vs1 1.46, 95% CI 1.18, 1.80) and with higher average temperatures (RR 1.05 95% CI 1.03, 1.08). Diabetes mortality was lower where consumption of alcohol was excessive (RRt3vs1 0.84, 95% CI 0.72, 0.99). No association was observed with smoking, overconsumption of red meat, high mean sedentary time, systolic blood pressure, cholesterol, and diabetes prevalence. CONCLUSIONS: Declines in diabetes mortality between 2006 and 2012 have been unequally distributed across China, which may imply differentials in diagnosis, management, and the provision of services that warrant further investigation. PMID- 26159912 TI - Structures and regulation of non-X orphan nuclear receptors: A retinoid hypothesis. AB - Nuclear receptors are defined as a family of ligand regulated transcription factors [1-6]. While this definition reflects that ligand binding is a key property of nuclear receptors, it is still a heated subject of debate if all the nuclear receptors (48 human members) can bind ligands (ligands referred here to both physiological and synthetic ligands). Recent studies in nuclear receptor structure biology and pharmacology have undoubtedly increased our knowledge of nuclear receptor functions and their regulation. As a result, they point to new avenues for the discovery and development of nuclear receptor regulators, including nuclear receptor ligands. Here we review the recent literature on orphan nuclear receptor structural analysis and ligand identification, particularly on the orphan nuclear receptors that do not heterodimerize with retinoid X receptors, which we term as non-X orphan receptors. We also propose a speculative "retinoid hypothesis" for a subset of non-X orphan nuclear receptors, which we hope to help shed light on orphan nuclear receptor biology and drug discovery. This article is part of a Special Issue entitled 'Orphan Nuclear Receptors'. PMID- 26159913 TI - Cholecalciferol (vitamin D3) improves functional recovery when delivered during the acute phase after a spinal cord trauma. AB - In a previous study, based on a rat model of thoracic spinal cord compression, we demonstrated that cholecalciferol (Vitamin D3), delivered at the dose of 200 IU/kg/day, significantly improved ventilatory frequency and spasticity. In order to confirm the restorative potential of vitamin D, we performed a new study, using a rat model of left cervical hemisection (C2). From Day 1 or Day 7, animals received, during three months, a weekly oral bolus of either cholecalciferol, at the dose of 500 IU/kg/day, or vehicle, namely triglycerides. Rats were assessed every month, using a ladder test for sensori-locomotor ability and neuromuscular capacity. Three months after injury, H-reflex was recorded from left extensor digitorum muscle in order to measure the reflexivity of the sub-lesional region. Ventilatory frequency was also monitored during an electrically induced muscle fatigue of the hindlimb known to enhance muscle metaboreflex and increase respiratory rate. After recording the phrenic nerve activity, ipsilateral to the lesion, during spontaneous breathing, animals were artificially ventilated while paralyzed with a neuromuscular blocking agent and then the brainstem respiratory centres were provoked to maximal output by temporarily stopping the ventilator. Spinal cords were immunostained with an anti-neurofilament antibody to evaluate axon numbers. We show here that vitamin D-treated animals display i) an enhanced locomotor activity, ii) an improved breathing when hindlimb muscle was electrically stimulated to induce fatigue, iii) an H-reflex depression similar to control animals, iv) a phrenic nerve activity response to a temporary asphyxial stress and v) a non significant decreased number of axons in the proximal stump when compared with the Sham group. This new set of data confirms that vitamin D is a potent molecule that could be tested in clinical trials assessing functional recovery in para-/tetra-plegic patients, shortly after a trauma. PMID- 26159914 TI - A Spatial Analysis of Heterogeneity in the Link Between Alcohol Outlets and Assault Victimization: Differences Across Victim Subpopulations. AB - The positive association between alcohol outlet density and assault rates is well established, but little is known about how this association differs across victim subpopulations. We use spatial point process models on police data from Flint, Michigan, to test how the link between alcohol outlet density and assault rates changes as a function of three victim characteristics: age, gender, and race. We found that, although both on-premises and package outlet densities consistently emerge as risk factors for victimization, their relative effects are markedly larger in Whites than in African Americans. No analogous age- or gender-based differences were found. These results suggest the racial effects arise more from relative differences in the atmosphere in and around alcohol outlets than differences in drinking behavior alone. PMID- 26159915 TI - Intraoperative Optical Coherence Tomography in Children with Anterior Segment Anomalies. PMID- 26159916 TI - LRIG1, a 3p tumor suppressor, represses EGFR signaling and is a novel epigenetic silenced gene in colorectal cancer. AB - Downregulation of LRIG1 was found in many types of cancer. However, data concerning the possible mechanism of LRIG1 reduction in cancers were not reported yet. To analyze the regulation and function of LRIG1 in colorectal cancer (CRC), 6 cell lines, 46 paired tissues from primary CRC cases were employed in this study. In CRC cell lines, under-expression of LRIG1 was correlated with promoter region hypermethylation, and restoration of LRIG1 was induced by 5-Aza-2' deoxyazacytidine treatment. Subsequently, we ectopically expressed LRIG1 in LRIG1 low-expressing HCT-116 cells and suppressed LRIG1 in LRIG1 high-expressing LoVo cells. We found that over-expression of LRIG1 inhibits cell proliferation and colony formation and tumor growth, while knockdown of LRIG1 promotes cell proliferation and colony formation. Decreased and increased EGFR/AKT signaling pathway may partially explain the lower and higher rates of proliferation in CRC cells transfected with LRIG1 cDNA or shRNA. In clinical samples, we compared the methylation, mRNA and protein expression of LRIG1 in samples of CRC tissues. A significant increase in LRIG1 methylation was identified in CRC specimens compared to adjacent normal tissues and that it was negatively correlated with its mRNA and protein expression. In conclusion, LRIG1 is frequently methylated in human CRC and consequent mRNA and protein downregulation may contribute to tumor growth by activating EGFR/AKT signaling. PMID- 26159917 TI - Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy. AB - Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1 methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-beta-galactosidase (SA-beta-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy. PMID- 26159918 TI - Unique MicroRNA signatures associated with early coronary atherosclerotic plaques. AB - The pathophysiology of coronary atherosclerotic plaques is a complex process. Early detection of coronary atherosclerotic plaques is critical in the prevention, prognostic and therapeutic intervention of cardiovascular disease. MicroRNAs (miRNAs), endogenous short non-coding RNAs, have been reported to play an important role in cardiovascular diseases and are also used as disease markers. However, the miRNA expression profile in early coronary atherosclerotic plaques has yet been reported. We hypothesize that miRNAs can be used as effective disease markers for detection of early coronary atherosclerotic plaques. In this analysis, coronary artery samples from three patients with early coronary atherosclerosis were harvested and miRNA expression profile determined using microarray analysis. Compared with healthy controls, a total of 44 miRNAs were upregulated and 57 miRNAs were downregulated. Among the dysregulated miRNAs, eight were significantly upregulated while five miRNAs were significantly downregulated, as determined by t-test (P < 0.05). Four of the significantly dysregulated miRNAs, including miR-221, miR-155, miR-100 and hsa-miR-1273, were selected and verified by real-time PCR. The real-time PCR results were consistent with the microarray data that miR-221, miR-155 and miR-100 were significantly downregulated in plaques, whereas miR-1273 was significantly upregulated. These results indicate that miRNAs expression level can be used as potential markers for early coronary atherosclerotic plaque formation. PMID- 26159920 TI - BAG3 affects the nucleocytoplasmic shuttling of HSF1 upon heat stress. AB - Bcl2-associated athoanogene (BAG) 3 is a member of the co-chaperone BAG family. It is induced by stressful stimuli such as heat shock and heavy metals, and it regulates cellular adaptive responses against stressful conditions. In this study, we identified a novel role for BAG3 in regulating the nuclear shuttling of HSF1 during heat stress. The expression level of BAG3 was induced by heat stress in HeLa cells. Interestingly, BAG3 rapidly translocalized to the nucleus upon heat stress. Immunoprecipitation assay showed that BAG3 interacts with HSF1 under normal and stressed conditions and co-translocalizes to the nucleus upon heat stress. We also demonstrated that BAG3 interacts with HSF1 via its BAG domain. Over-expression of BAG3 down-regulates the level of nuclear HSF1 by exporting it to the cytoplasm during the recovery period. Depletion of BAG3 using siRNA results in reduced nuclear HSF1 and decreased Hsp70 promoter activity. BAG3 in MEF(hsf1(-/-)) cells actively translocalizes to the nucleus upon heat stress suggesting that BAG3 plays a key role in the processing of the nucleocytoplasmic shuttling of HSF1 upon heat stress. PMID- 26159919 TI - Activation of human natural killer cells by the soluble form of cellular prion protein. AB - Cellular prion protein (PrP(C)) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP(C) in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP(C) protein on human natural killer (NK) cells. Recombinant soluble PrP(C) protein was generated by fusion of human PrP(C) with the Fc portion of human IgG1 (PrP(C)-Fc). PrP(C)-Fc binds to the surface of human NK cells, particularly to CD56(dim) NK cells. PrP(C)-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP(C)-Fc facilitated the IL-15-induced proliferation of NK cells. PrP(C)-Fc induced phosphorylation of ERK 1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP(C)-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP(C)-Fc protein activates human NK cells via the ERK and JNK signaling pathways. PMID- 26159921 TI - XRN2 is required for the degradation of target RNAs by RNase H1-dependent antisense oligonucleotides. AB - Antisense oligonucleotides (ASOs) can suppress the expression of a target gene by cleaving pre-mRNA and/or mature mRNA via RNase H1. Following the initial endonucleolytic cleavage by RNase H1, the target RNAs are degraded by a mechanism that is poorly understood. To better understand this degradation pathway, we depleted the expression of two major 5' to 3' exoribonucleases (XRNs), named XRN1 and XRN2, and analyzed the levels of 3' fragments of the target RNAs in vitro. We found that the 3' fragments of target pre-mRNA generated by ASO were almost completely degraded from their 5' ends by nuclear XRN2 after RNase H1-mediated cleavage, whereas the 3' fragments of mature mRNA were partially degraded by XRN2. In contrast to ASO, small interference RNA (siRNA) could reduce the expression level of only mature mRNA, and the 3' fragment was degraded by cytoplasmic XRN1. Our findings indicate that the RNAs targeted by RNase H1 dependent ASO are rapidly degraded in the nucleus, contrary to the cytoplasmic degradation pathway mediated by siRNA. PMID- 26159923 TI - Elevated Rictor expression is associated with tumor progression and poor prognosis in patients with gastric cancer. AB - The rapamycin insensitive companion of mTOR (Rictor) is an essential subunit of mTOR complex 2 (mTORC2), maintains the integrity of the complex and functions as regulator of Akt full activation. Rictor has been implicated to be involved in growth and progression of malignancies, however, little is known about its expression and prognostic role in gastric cancer in particular. Therefore, we investigated the relationship of Rictor expression with clinical outcomes, together with pAktSer473 and pS6, two downstream substrates of mTORC2 and mTORC1, in 396 gastric cancer tissue samples via immunohistochemistry. The results showed that 74.0% and 55.8% of tumors were Rictor and pAktSer473 positive staining, respectively, which correlated well with each other. Patients with positive expressions had poorer overall survival and relapse-free survival compared with those negative staining. Both Rictor and pAktSer473 expression were associated with lymph node metastasis, TNM stage, and WHO grading. Rictor was also correlated with tumor size, depth of invasion, and tumor thrombus, while pAktSer473 was also correlated with distant metastasis. In spite of 67.4% expression rate was presented in gastric cancer tissues, no significant association was observed between pS6Ser235/236, representing mTORC1 activity, and clinicopathological features or prognosis. These results suggest that mTORC2/Rictor/pAkt may play a more important role than mTORC1/pS6 in tumor progression, which could act as a prognostic biomarker or potential therapeutic target in gastric cancer. PMID- 26159922 TI - The PGC-1 coactivators promote an anti-inflammatory environment in skeletal muscle in vivo. AB - The peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC 1alpha) is abundantly expressed in trained muscles and regulates muscle adaptation to endurance exercise. Inversely, mice lacking a functional PGC-1alpha allele in muscle exhibit reduced muscle functionality and increased inflammation. In isolated muscle cells, PGC-1alpha and the related PGC-1beta counteract the induction of inflammation by reducing the activity of the nuclear factor kappaB (NFkappaB). We now tested the effects of these metabolic regulators on inflammatory reactions in muscle tissue of control and muscle-specific PGC 1alpha/-1beta transgenic mice in vivo in the basal state as well as after an acute inflammatory insult. Surprisingly, we observed a PGC-1-dependent alteration of the cytokine profile characterized by an increase in anti-inflammatory factors and a strong suppression of the pro-inflammatory interleukin 12 (IL-12). In conclusion, the anti-inflammatory environment in muscle that is promoted by the PGC-1s might contribute to the beneficial effects of these coactivators on muscle function and provides a molecular link underlying the tight mutual regulation of metabolism and inflammation. PMID- 26159924 TI - mTORC1 signaling in Agrp neurons mediates circadian expression of Agrp and NPY but is dispensable for regulation of feeding behavior. AB - Orexigenic agouti-related protein/neuropeptide Y (Agrp/NPY) neurons and an orexigenic pro-opiomelanocortin (POMC) neurons of the hypothalamus regulate feeding behavior and energy homeostasis. An understanding of the molecular signaling pathways that regulate Agrp/NPY and POMC function could lead to novel treatments for metabolic disorders. Target of Rapamycin Complex 1 (TORC1) is a nutrient-activated protein kinase and central controller of growth and metabolism. We therefore investigated the role of mammalian TORC1 (mTORC1) in Agrp neurons. We generated and characterized Agrp neuron-specific raptor knockout (Agrp-raptor KO) mice. Agrp-raptor KO mice displayed reduced, non-circadian expression of Agrp and NPY but normal feeding behavior and energy homeostasis on both normal and high fat diet. Thus, mTORC1 in Agrp neurons controls circadian expression of orexigenic neuropeptides but is dispensable for the regulation of feeding behavior and energy metabolism. PMID- 26159925 TI - TLR4 plays a crucial role in MSC-induced inhibition of NK cell function. AB - Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC. MSC was reported to inhibit natural killer (NK) cell proliferation and function. In this research, we confirmed that TLR4+ MSC aggravate this suppression. Furthermore, when TLR4 in the sorted cells were stimulated by LPS or following blocked by antibody, the suppression on NK cell proliferation and cytotoxicity were more intensive or recovered respectively. Compared to unsorted MSC, NKG2D receptor expression on NK cells were also inhibited by TLR4+ MSC. These findings suggest that activation of TLR4 pathway is important for TLR4+ MSC and MSC to obstruct anti-tumor immunity by inhibiting NK cell function, which may provide a potential stroma-targeted tumor therapy. PMID- 26159926 TI - Novel insights into the apoptosis mechanism of DNA topoisomerase I inhibitor isoliquiritigenin on HCC tumor cell. AB - The inhibitory effect of DNA topoisomerase (Top I) by isoliquiritigenin(ISO) were investigated and their interaction mechanism was evaluated using methods including UV-vis absorption, fluorescence, coupled with molecular simulation, and using the MTT method of inhibition rate of HCC tumor cell SNU475 proliferation assay, finally, the interaction of ISO with calf thymus DNA was investigated by melting measurements and molecular docking studies. It was found that isoliquiritigenin reversibly inhibited DNA Top I in a competitive manner with the concentrations of ISO resulting in 50% activity lost (IC50) were estimated to be 0.178 +/- 0.12 mM. Isoliquiritigenin exhibited a strong ability to quench the intrinsic fluorescence of Top I through a static quenching procedure. The positive values of enthalpy change and entropy change suggested that the binding of isoliquiritigenin to Top I was driven mainly by hydrophobic interactions. The molecular docking results revealed isoliquiritigenin actually interacted with the primary amino acid residues on the active site of Top I, and the detection results of fluorescence staining and the inhibitory effect on the growth of HCC SUN475 showed that isoliquiritigenin induced the apoptosis cells increased gradually. The interaction of ISO with DNA can cause the denaturation temperature to be increased, which indicated that the stabilization of the DNA helix was increased in the presence of ISO, which indicated that the results provide strong evidence for intercalative binding of ISO with DNA. PMID- 26159927 TI - Intranuclear interactomic inhibition of NF-kappaB suppresses LPS-induced severe sepsis. AB - Suppression of nuclear factor-kappaB (NF-kappaB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-kappaB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-alpha, IL-1beta, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF kappaB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-gamma, IL-4, IL-17A, or IL-10. Systemic administration of nt p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. PMID- 26159928 TI - Low alpha-synuclein levels in the blood are associated with insulin resistance. AB - Mutations in the protein alpha-synuclein (SNCA) have been linked to Parkinson's disease. We recently reported that non-mutated SNCA enhanced glucose uptake through the Gab1-PI3 kinase-Akt pathway and elucidated its effects on glucose regulation. Here, we examined the association of SNCA with insulin resistance (IR), a condition that is characterized by decreased tissue glucose uptake. Our observations include those from a population study as well as a SNCA-deficient mouse model, which had not previously been characterized in an IR scenario. In 1,152 patients, we found that serum SNCA levels were inversely correlated with IR indicators--body mass index, homeostatic model assessment for IR (HOMA-IR) and immunoreactive insulin (IRI)--and, to a lesser extent, with blood pressure and age. Additionally, SNCA-deficient mice displayed alterations in glucose and insulin responses during diet-induced IR. Moreover, during euglycemic clamp assessments, SNCA knock-out mice fed a high-fat diet (HFD) showed severe IR in adipose tissues and skeletal muscle. These findings provide new insights into IR and diabetes and point to SNCA as a potential candidate for further research. PMID- 26159930 TI - Photoactivation of TAZ via Akt/GSK3beta signaling pathway promotes osteogenic differentiation. AB - Osteogenesis disorder is involved in osteoporosis and other related bone diseases, in which osteogenic differentiation is essential. Osteogenic differentiation is a complicated process regulated by intricate signal transduction networks. It has been reported that low-power laser irradiation (LPLI) has an osteogenic potential by promoting osteoblast differentiation. However, the molecular mechanisms remain to be understood. In this study, we reveal a novel mechanism that Akt/GSK3beta/TAZ (transcriptional co-activator with PDZ-binding motif) signaling pathway plays a crucial role in LPLI-enhanced osteoblast differentiation. Photomodulation by LPLI activated Akt/GSK3beta pathway which inhibited TAZ phosphorylation, leading to the increase of TAZ protein level and nuclear aggregation. Meanwhile, knockdown of TAZ suppressed osteogenic differentiation promoted by LPLI. Further study showed that LPLI promoted the interaction between TAZ and core-binding factor 1 (Cbfa1), up regulating the transcription of osteopontin (OPN) and osteocalcin (OCN) and the activity of alkaline phosphatase (ALP). However, inhibition of Akt/GSK3beta pathway reversed the effects of TAZ on osteogenic differentiation induced by LPLI. Taken together, for the first time, we report that LPLI promotes osteoblast differentiation via TAZ activation dependent on Akt/GSK3beta signaling pathway. PMID- 26159929 TI - Functional roles of non-coding Y RNAs. AB - Non-coding RNAs are involved in a multitude of cellular processes but the biochemical function of many small non-coding RNAs remains unclear. The family of small non-coding Y RNAs is conserved in vertebrates and related RNAs are present in some prokaryotic species. Y RNAs are also homologous to the newly identified family of non-coding stem-bulge RNAs (sbRNAs) in nematodes, for which potential physiological functions are only now emerging. Y RNAs are essential for the initiation of chromosomal DNA replication in vertebrates and, when bound to the Ro60 protein, they are involved in RNA stability and cellular responses to stress in several eukaryotic and prokaryotic species. Additionally, short fragments of Y RNAs have recently been identified as abundant components in the blood and tissues of humans and other mammals, with potential diagnostic value. While the number of functional roles of Y RNAs is growing, it is becoming increasingly clear that the conserved structural domains of Y RNAs are essential for distinct cellular functions. Here, we review the biochemical functions associated with these structural RNA domains, as well as the functional conservation of Y RNAs in different species. The existing biochemical and structural evidence supports a domain model for these small non-coding RNAs that has direct implications for the modular evolution of functional non-coding RNAs. PMID- 26159931 TI - Passive Hind-Limb Cycling Reduces the Severity of Autonomic Dysreflexia After Experimental Spinal Cord Injury. AB - BACKGROUND: Spinal cord injury (SCI) induces alterations in cardio-autonomic control of which autonomic dysreflexia (AD), a condition characterized by life threatening hypertension, is arguably the most insidious. Passive hind-limb cycling represents a low-cost therapeutic intervention with demonstrable cardiovascular, sensory, and motor benefits. OBJECTIVE: To investigate the effect of passive hind-limb cycling on AD in rodents with T3 SCI. METHODS: Forty-five male Wistar rats were evenly assigned to either uninjured control (CON), SCI, or SCI plus hind-limb cycling exercise (SCI-EX). At the end of the experimental period (day 32), rats were randomly assigned to stream 1 (n = 24) or stream 2 (n = 21). Stream 1 rats were assessed for AD severity (pressor response to colorectal distension) and were then perfused for tissue dissection and immunohistochemistry. Stream 2 rats underwent excision of the superior mesenteric artery for in vitro myography assessments. RESULTS: From 2 weeks post-SCI onwards, SCI-EX rats exhibited a significant reduction in the pressor response to colorectal distension versus SCI (P< .001). Reduced AD severity in SCI-EX rats was accompanied by a prevention of the SCI-induced increase in density of CGRP(+)afferents in the dorsal horn (P= .001). Conversely, both SCI and SCI-EX rats exhibited a similar degree of mesenteric endothelial dysfunction and alpha adrenoceptor hypersensitivity versus CON. CONCLUSION: Passive hind-limb cycling reduces the severity of AD in SCI, and is correlated with changes in primary afferent morphology, but has limited effects on the peripheral vasculature. PMID- 26159932 TI - Serum Soluble Klotho Level Is Associated with Abdominal Aortic Calcification in Patients on Maintenance Hemodialysis. AB - BACKGROUND: Klotho is a single transmembrane protein originally identified as an 'aging suppressor'. Emerging evidence reveals that soluble Klotho (sKl) in the circulation plays important roles in anti-aging, anti-oxidation, anti-apoptosis and Wnt signaling. However, the role of serum sKl in the vascular calcification in hemodialysis patients is not clear. The aim of this study was to determine the associations of sKl with abdominal aortic calcification in patients on maintenance hemodialysis (MHD). METHODS: 129 MHD patients were enrolled prospectively. Serum sKl level was detected by ELISA. Abdominal aortic calcification was measured by abdomen lateral plain radiograph, and the abdominal aorta calcification (AAC) score was calculated. The sKl levels were observed in patients with different degrees of calcification. Logistic regression analysis was used to determine the risk factor of abdominal aortic calcification in MHD patients. The diagnostic value of sKl for abdominal aortic calcification was assessed using receiver operator characteristic (ROC). RESULTS: Abdominal aortic calcification was seen in 87 of 129 patients. The median AAC score was 4.0 (0.00, 11.00) and the median sKl level was 616.29 (378.19, 821.61) pg/ml. Serum sKl levels were inversely associated with AAC. When evaluated as AAC categories (<5, 5-15, >15) with ordinal logistic regression, each SD higher sKl was associated with 37.1% lower odds of AAC severity (proportional odds ratio: 0.629; 95% confidence interval: 0.413-0.959, p = 0.031) in models adjusted for demographic data, lifestyle factors, traditional CVD risk factors and uremic risk factors. Multivariate logistic regression analysis showed that serum sKl levels and smoking were independent risk factors for severe AAC. The area under the receiver operating characteristic curve (AUC) of serum sKl for severe abdominal aortic calcification was 0.746 (0.612-0.880, p = 0.001), sensitivity was 0.885, and specificity was 0.562 for a cutoff value of 265.39 pg/ml. CONCLUSIONS: Lower serum sKl levels are independently associated with severe AAC. Serum sKl might have a diagnostic value for the severe AAC in MHD patients. PMID- 26159933 TI - The impact of sodium nitroprusside and ozone in kiwifruit ripening physiology: a combined gene and protein expression profiling approach. AB - BACKGROUND AND AIMS: Despite their importance in many aspects of plant physiology, information about the function of oxidative and, particularly, of nitrosative signalling in fruit biology is limited. This study examined the possible implications of O3 and sodium nitroprusside (SNP) in kiwifruit ripening, and their interacting effects. It also aimed to investigate changes in the kiwifruit proteome in response to SNP and O3 treatments, together with selected transcript analysis, as a way to enhance our understanding of the fruit ripening syndrome. METHODS: Kiwifruits following harvest were pre-treated with 100 MUm SNP, then cold-stored (0 degrees C, relative humidity 95 %) for either 2 or 6 months in the absence or in the presence of O3 (0.3 MUL L(-1)), and subsequently were allowed to ripen at 20 degrees C. The ripening behaviour of fruit was characterized using several approaches: together with ethylene production, several genes, enzymes and metabolites involved in ethylene biosynthesis were analysed. Kiwifruit proteins were identified using 2-D electrophoresis coupled with nanoliquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Expression patterns of kiwifruit ripening-related genes were also analysed using real-time quantitative reverse transcription-PCR (RT-qPCR). KEY RESULTS: O3 treatment markedly delayed fruit softening and depressed the ethylene biosynthetic mechanism. Although SNP alone was relatively ineffective in regulating ripening, SNP treatment prior to O3 exposure attenuated the O3-induced ripening inhibition. Proteomic analysis revealed a considerable overlap between proteins affected by both SNP and O3. Consistent with this, the temporal dynamics in the expression of selected kiwifruit ripening-related genes were noticeably different between individual O3 and combined SNP and O3 treatments. CONCLUSIONS: This study demonstrates that O3-induced ripening inhibition could be reversed by SNP and provides insights into the interaction between oxidative and nitrosative signalling in climacteric fruit ripening. PMID- 26159934 TI - Biotic context and soil properties modulate native plant responses to enhanced rainfall. AB - BACKGROUND AND AIMS: The environmental and biotic context within which plants grow have a great potential to modify responses to climatic changes, yet few studies have addressed both the direct effects of climate and the modulating roles played by variation in the biotic (e.g. competitors) and abiotic (e.g. soils) environment. METHODS: In a grassland with highly heterogeneous soils and community composition, small seedlings of two native plants, Lasthenia californica and Calycadenia pauciflora, were transplanted into factorially watered and fertilized plots. Measurements were made to test how the effect of climatic variability (mimicked by the watering treatment) on the survival, growth and seed production of these species was modulated by above-ground competition and by edaphic variables. KEY RESULTS: Increased competition outweighed the direct positive impacts of enhanced rainfall on most fitness measures for both species, resulting in no net effect of enhanced rainfall. Both species benefitted from enhanced rainfall when the absence of competitors was accompanied by high soil water retention capacity. Fertilization did not amplify the watering effects; rather, plants benefitted from enhanced rainfall or competitor removal only in ambient nutrient conditions with high soil water retention capacity. CONCLUSIONS: The findings show that the direct effects of climatic variability on plant fitness may be reversed or neutralized by competition and, in addition, may be strongly modulated by soil variation. Specifically, coarse soil texture was identified as a factor that may limit plant responsiveness to altered water availability. These results highlight the importance of considering the abiotic as well as biotic context when making future climate change forecasts. PMID- 26159935 TI - Associations Between Glycemic Control, Depressed Mood, Clinical Depression, and Diabetes Distress Before and After Insulin Initiation: An Exploratory, Post Hoc Analysis. AB - INTRODUCTION: Although depression is often associated with poor glycemic control in patients with type 2 diabetes mellitus (T2DM), this observation has been inconsistent. This exploratory, post hoc analysis investigated associations between depression parameters and glycemic control using data from a 24-month, prospective, observational, non-interventional study evaluating glycemic response following insulin initiation for T2DM. METHODS: We analyzed data from a 24-month, prospective, observational study that evaluated glycemic response in patients with T2DM who initiated insulin therapy (N = 985) in 5 European countries. Secondary measures included patient-reported diagnosis of depression at baseline, severity of depressed/anxious mood (EuroQol (EQ)-5D item) and diabetes-related distress (Psychological Distress domain of the Diabetes Health Profile, DHP-18). The latter two measures were assessed at baseline and 5 time points throughout the study. Glycemic control was measured by glycated hemoglobin (HbA1c) at these same time points. Analyses employed t tests to assess the unadjusted baseline difference in HbA1c between patients with and without the respective depression parameter. The potential effect of demographic and clinical confounding variables was controlled through a linear model structure. Patient HbA1c levels were analyzed by presence/absence of a history of diagnosed depression, depressed mood, and diabetes-related distress. RESULTS: Patients with higher depression parameters or distress at baseline had significantly higher rates of microvascular complications at baseline. Patients with a history of diagnosed depression or high diabetes-related distress had higher HbA1c than patients without. HbA1c of patients with or without depressed mood was not significantly different at baseline. The proportion of patients with depressed mood declined after insulin initiation, whereas the proportion of patients with high diabetes related distress did not significantly change. HbA1c improved following insulin initiation, regardless of presence/absence of studied depression/distress parameters at baseline. CONCLUSION: History of diagnosed depression, diabetes related distress, and depressed mood were associated with a higher rate of microvascular complications. Diagnosed depression and diabetes-related distress also showed higher HbA1c at baseline when insulin was initiated. Insulin therapy improved glycemic control, while preexisting depressed mood declined and diabetes related distress remained unchanged. PMID- 26159936 TI - Ultrastrong ductile and stable high-entropy alloys at small scales. AB - Refractory high-entropy alloys (HEAs) are a class of emerging multi-component alloys, showing superior mechanical properties at elevated temperatures and being technologically interesting. However, they are generally brittle at room temperature, fail by cracking at low compressive strains and suffer from limited formability. Here we report a strategy for the fabrication of refractory HEA thin films and small-sized pillars that consist of strongly textured, columnar and nanometre-sized grains. Such HEA pillars exhibit extraordinarily high yield strengths of ~ 10 GPa--among the highest reported strengths in micro-/nano-pillar compression and one order of magnitude higher than that of its bulk form--and their ductility is considerably improved (compressive plastic strains over 30%). Additionally, we demonstrate that such HEA films show substantially enhanced stability for high-temperature, long-duration conditions (at 1,100 degrees C for 3 days). Small-scale HEAs combining these properties represent a new class of materials in small-dimension devices potentially for high-stress and high temperature applications. PMID- 26159937 TI - America vs Europe and the 2014 Non-ST Elevation Acute Coronary Syndrome Guidelines. AB - In August of 2014, the American Heart Association and American College of Cardiology (AHA/ACC) published a new guideline for the management of patients with non-ST-elevation acute coronary syndromes. With similar timing, the European Association for Cardio-Thoracic Surgery (EACTS) released new 2014 guidelines on myocardial revascularization, including a brief update on the 2011 European Society of Cardiology guidelines on the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. We briefly summarize key components of all three of these guideline publications, highlighting differences and concluding that similarities far outweigh differences in the American vs European approach to a patient with non-ST-elevation acute coronary syndrome. PMID- 26159939 TI - Effect of a single dose of Saccharomyces cerevisiae var. boulardii on the occurrence of porcine neonatal diarrhoea. AB - Piglet neonatal diarrhoea is an important issue in modern pig production and is linked to increased mortality and poor growth rates, affecting long-term pig health, increasing use of medication and cost of production. Saccharomyces cerevisiae var. boulardii (SB) is a probiotic yeast with documented clinical efficacy in the prevention and treatment of diarrhoeal diseases in humans. The objectives of the current study were to evaluate the effect of SB on occurrence and severity of neonatal diarrhoea in piglets, mortality and growth rate. Forty six litters (606 piglets) were randomly allocated to a control or SB treatment (n=23 per treatment). Within 24 h of farrowing, piglets assigned to the SB treatment received a single oral dose of a paste containing 3.3*10(9) CFU of SB CNCM I-107(9). Piglets from the control litters received a placebo paste. Piglet weight, mortality and diarrhoea were recorded up to day 7 of age. It was shown that numbers of diarrhoea days were significantly correlated with increased mortality rate and reduced weight gain (P<0.05). SB treatment had no effect on growth or mortality in diarrhoeic litters. However, SB-supplemented litters had significantly lower faecal scores, indicating firmer faeces (P<0.01) and fewer numbers of diarrhoeic days (P<0.01) during the 1(st) week of life. Reduction in the number of diarrhoeic litters compared with the control group was observed following the probiotic administration (P<0.05). These results highlight the detrimental effects of neonatal diarrhoea on pre-weaning performance and suggest that SB, by reducing diarrhoea duration and severity, has the potential of improving enteric health in the early stages of life in pigs. PMID- 26159940 TI - Contribution of occupational health for prevention of work-related cardiovascular disorders (WR-CVDS). PMID- 26159941 TI - Prevention and management of work-related cardiovascular disorders. AB - Cardiovascular disorders (CVDs) constitute a major burden for health of working populations throughout the world with as much as 50% of all causes of death and at least 25% of work disability. There are some changes in CVD risk factors among occupational classes. This is mainly due to the new types of work-related causes of morbidity associated with the recent developments in global work life, particularly in the industrialized countries. Meanwhile, in the developing countries or those in transition (e.g., in Eastern Europe), CVD mortality is increasing due to major socioeconomic changes, the demographic transition and rapid industrialisation and urbanisation, all leading to growing challenges to cardiovascular health. Better control of known risk factors (i.e., smoking, obesity, physical inactivity, high cholesterol, high blood pressure, and high blood glucose) is effective to prevent CVD incidence. But the expected improvement has not been achieved. The obstacles of achieving such impact are due to lack of awareness, lack of policies and their implementation into practice and shortage of infrastructures and human resources. These are needed for wide-scale and long-term programme implementation. Considering the WHO Global Strategy on Occupational Health for All, the WHO Global Action Plan on Workers' Health, the WHO Programme on Prevention of Non-communicable Diseases and the ILO Decent Work agenda, the 6th ICOH International Conference on Work Environment and Cardiovascular Diseases adopted the Tokyo Declaration. PMID- 26159938 TI - Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame. AB - The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio. PMID- 26159942 TI - Work stress and the risk of recurrent coronary heart disease events: A systematic review and meta-analysis. AB - Though much evidence indicates that work stress increases the risk of incident of coronary heart disease (CHD), little is known about the role of work stress in the development of recurrent CHD events. The objective of this study was to review and synthesize the existing epidemiological evidence on whether work stress increases the risk of recurrent CHD events in patients with the first CHD. A systematic literature search in the PubMed database (January 1990 - December 2013) for prospective studies was performed. Inclusion criteria included: peer reviewed English papers with original data, studies with substantial follow-up (> 3 years), end points defined as cardiac death or nonfatal myocardial infarction, as well as work stress assessed with reliable and valid instruments. Meta analysis using random-effects modeling was conducted in order to synthesize the observed effects across the studies. Five papers derived from 4 prospective studies conducted in Sweden and Canada were included in this systematic review. The measurement of work stress was based on the Demand- Control model (4 papers) or the Effort-Reward Imbalance model (1 paper). According to the estimation by meta-analysis based on 4 papers, a significant effect of work stress on the risk of recurrent CHD events (hazard ratio: 1.65, 95% confidence interval: 1.23-2.22) was observed. Our findings suggest that, in patients with the first CHD, work stress is associated with an increased relative risk of recurrent CHD events by 65%. Due to the limited literature, more well-designed prospective research is needed to examine this association, in particular, from other than western regions of the world. PMID- 26159943 TI - Non-communicable diseases in the Asia-Pacific region: Prevalence, risk factors and community-based prevention. AB - Non-communicable diseases (NCDs) lead to substantial mortality and morbidity worldwide. The most common NCDs are cardiovascular diseases (CVD), diabetes, cancer and chronic respiratory diseases. With the rapid increase in NCD-related deaths in Asia Pacific countries, NCDs are now the major cause of deaths and disease burden in the region. NCDs hamper achievement of the Millennium Development Goals (MDG). People in the low socio-economic group are most affected by NCDs as they have poor access to policies, legislations, regulations and healthcare services meant to combat NCDs. This results in loss of productivity by a decreasing labor force with implications at the macroeconomic level. The 3 major NCDs in the Asia Pacific region are CVDs, cancer and diabetes due to the increasing loss of disability adjusted life years (DALYs). The 4 major behavioral risk factors for NCDs are: tobacco use, alcohol consumption, inadequate physical activity and unhealthy diet. The underlying risk factors are urbanization, globalization, sedentary lifestyle, obesity and hypertension. Strategies to combat NCDs in the Asia Pacific region are as follows: population-based dietary salt reduction, health education, psychological interventions, i.e., cognitive behavioral therapy and motivational-interviewing, taxation and bans on tobacco related advertisements, implementing smoke-free zones and surveillance by the World Health Organization. Control measures must focus on prevention and strengthening inter-sectorial collaboration. PMID- 26159944 TI - Impedance cardiography - Old method, new opportunities. Part I. Clinical applications. AB - Monitoring of cardiovascular hemodynamic changes requires a very expensive and highly specialized equipment and skilled medical personnel. Up to the present time, an inexpensive, non-invasive and easy-to-use method which, like Doppler echocardiography, magnetic resonance angiography or radionuclide imaging, would assess hemodynamics of the cardiovascular system was not available. A method known as impedance cardiography (ICG) or thoracic electrical bioimpedance cardiography (TEBC) meets those criteria. It is non-invasive, which is of a particular advantage over the conventional methods that require catheterization. As a result, the patient is not at risk of possible complications and the procedure is less expensive and easier. Impedance cardiography, despite its non invasive character, has not been so far extensively used for monitoring of hemodynamic parameters in hospitalized patients. Various authors report that attempts have been continued to compare the results from ICG and those obtained by other diagnostic methods. This paper presents the use of impedance cardiography in diagnosis of hypertension, cardiac insufficiency, differentiating the causes of acute dyspnea, as well as in assessing the effects of cardiac rehabilitation in patients with heart failure. PMID- 26159945 TI - Impedance cardiography - Old method, new opportunities. Part II. Testing of cardiovascular response to various factors of work environment. AB - Impedance cardiography seems to be a very good, although underappreciated diagnostic method. What may distinguish it from among the many research methods is the fact that it enables non-invasive monitoring of cardiac output, stroke volume and systemic vascular resistance. Holter recording of the hemodynamic parameters makes it possible to study them not only in stationary (hospital, outpatient clinic) conditions, but also during household or professional activities, e.g., during road vehicle driving. Assessment of the trends of changes in the circulatory system of the employee at work makes it possible to judge whether the type of work performed by the worker is well tolerated - whether it is not too hard or too stressful. This is important, therefore, impedance cardiography can be extensively used in occupational medicine. Provision of preventive care to workers according to current standards requires, on the one hand, the use of the latest diagnostic methods while, on the other hand, the methods must be inexpensive, because otherwise the employer would not be able or willing to pay the associated costs. Impedance cardiography meets those criteria; however, few data is available in literature worldwide on the use of this method in the research on the impact of occupational work on cardiovascular responses of the employees. This work reports the use of impedance cardiography in studies on the various aspects of work environment. PMID- 26159946 TI - Prolonged job strain reduces time-domain heart rate variability on both working and resting days among cardiovascular-susceptible nurses. AB - INTRODUCTION: Modifications of hearth rate variability (HRV) constitute a marker of the autonomic nervous system (ANS) deregulation, a promising pathway linking job strain (JS) and cardiovascular diseases (CVD). The study objective is to assess whether exposures to recent and prolonged JS reduce time-domain HRV parameters on working days (WD) among CVD-susceptible nurses and whether the association also persists on resting days (RD). MATERIAL AND METHODS: 313 healthy nurses were investigated twice with one year interval to assess JS based on the demand-control and the effort-reward models. 36, 9 and 16 CVD-susceptible nurses were classified as low JS in both surveys (stable low strain - SLS), recent high JS (high JS at the second screening only-RHS) and prolonged high JS (high strain in both surveys-PHS), respectively. In 9, 7 and 10 of them, free from comorbidities/treatments interfering with HRV, two 24-h ECG recordings were performed on WD and RD. Differences in the time domain HRV metrics among JS categories were assessed using ANCOVA, adjusted for age and smoking. RESULTS: In the entire sample (mean age: 39 years, 83% females) the prevalence of high job strain was 38.7% in the second survey. SDNN (standard deviation of all normal RR intervals) on WD significantly declined among JS categories (p = 0.02), with geometric mean values of 169.1, 145.3 and 128.9 ms in SLS, RHS, PHS, respectively. In the PHS group, SDNN remained lower on RD as compared to the low strain subjects (142.4 vs. 171.1 ms, p = 0.02). Similar findings were found for the SDNN_Index, while SDANN (standard deviation of average RR intervals in all 5 min segments of registration) mean values reduced in the PHS group during WD only. CONCLUSIONS: Our findings suggest that persistent JS lowers HRV time-domain parameters, supporting the hypothesis that the ANS disorders may play an intermediate role in the relationship between work stress and CVD. PMID- 26159947 TI - Return to work after coronary revascularization procedures and a patient's job satisfaction: A prospective study. AB - INTRODUCTION: Research into work reintegration following invasive cardiac procedures is limited. The aim of this prospective study was to explore predictors of job satisfaction among cardiac patients who have returned to work after cardiac rehabilitation (CR). MATERIAL AND METHODS: The study population consisted of 90 cardiac patients who have recently been treated with coronary angioplasty or heart surgery. They were evaluated during their CR and 12 months after the discharge using validated self-report questionnaires measuring job satisfaction, work stress-related factors, emotional distress and illness perception. Information on socio-demographic, medical and occupational factors has also been collected. RESULTS: After adjusting for demographic, occupational and medical variables, baseline job satisfaction (p < 0.001), depression (p < 0.01) and ambition (p < 0.05) turned out to be independent, significant predictors of job satisfaction following return to work (RTW). Patients who had a partial RTW were more satisfied with their job than those who had a full RTW, controlling for baseline job satisfaction. CONCLUSIONS: These findings recommend an early assessment of patients' psychosocial work environment and emotional distress, with particular emphasis on job satisfaction and depressive symptoms, in order to promote satisfying and healthy RTW after cardiac interventions. PMID- 26159948 TI - Impairment of pulmonary function and changes in the right cardiac structure of pneumoconiotic coal workers in China. AB - INTRODUCTION: Information on the changes of pulmonary function and the right cardiac structure in patients with coal worker's pneumoconiosis in China is very scarce. This study was performed to clarify the changes of pulmonary function and right cardiac structure in patients with coal worker's pneumoconiosis in China. MATERIAL AND METHODS: Pulmonary function, pulmonary artery systolic pressure, and the right cardiac structure were evaluated by spirometry and color Doppler echocardiography. RESULTS: The pulmonary artery systolic pressure of patients with coal worker's pneumoconiosis was increased with disease severity. Patients with coal worker's pneumoconiosis also exhibited an impaired pulmonary function and altered right cardiac structure compared with control subjects. A significant linear correlation of the variables of pulmonary ventilation and diffusion function with the indicators of the right cardiac structure was found in patients with coal worker's pneumoconiosis in China. CONCLUSIONS: This study elucidated a deterioration of pulmonary function and right cardiac structure in patients with coal worker's pneumoconiosis in China. PMID- 26159950 TI - Exhaled breath malondialdehyde, spirometric results and dust exposure assessment in ceramics production workers. AB - INTRODUCTION: The study aimed at measuring exhaled breath malondialdehyde (EBC MDA) in workers exposed to dust containing silica and at its comparison with the non-exposed control group. MATERIAL AND METHODS: The cross sectional, case control study (N = 50) was performed in a tile and ceramics production factory in Yazd, Iran. EBC-MDA was quantified in exhaled breath of the participants by a lab made breath sampler. Exposure intensity was measured according to the NIOSH 0600 method in selected homogeneous exposure groups. Additionally, spirometry test was conducted to investigate a correlation between EBC-MDA and spirometric findings in the exposed workers. RESULTS: There was no difference in the observed exposure intensities of silica containing dust in different units. However, "coating preparation" was the unit with the highest concentration of dust. Although, the level of EBC-MDA in the cases was slightly higher than in the controls, the difference was not statistically significant (U = 252, p = 0.464). A significant and positive correlation was found between dust exposure intensity in working units and the measured EBC-MDA of workers (r = 0.467, N = 25, p = 0.027). There were also no statistically significant differences among job categories in the exposed group for the values of FEV1% (F(3, 44) = 0.656, p = 0.584), FVC% (F(3, 44) = 1.417, p = 0.172), and FEV1/FVC% (F(3, 44) = 1.929, p = 0.139). CONCLUSIONS: The results showed a significant correlation between respirable dust exposure intensity and the level of EBC-MDA of the exposed subjects. However, our results did not show a significant correlation between lung function decreases and EBC-MDA. PMID- 26159949 TI - Pressure drop of filtering facepiece respirators: How low should we go? AB - INTRODUCTION: This study was undertaken to determine the mean peak filter resistance to airflow (Rfilter) encountered by subjects while wearing prototype filtering facepiece respirators (PRs) with low Rfilter during nasal and oral breathing at sedentary and low-moderate work rates. MATERIAL AND METHODS: In-line pressure transducer measurements of mean Rfilteracross PRs with nominal Rfilter of 29.4 Pa, 58.8 Pa and 88.2 Pa (measured at 85 l/min constant airflow) were obtained during nasal and oral breathing at sedentary and low-moderate work rates for 10 subjects. RESULTS: The mean Rfilter for the 29.4 PR was significantly lower than the other 2 PRs (p < 0.000), but there were no significant differences in mean Rfilter between the PRs with 58.8 and 88.2 Pa filter resistance (p > 0.05). The mean Rfilter was greater for oral versus nasal breathing and for exercise compared to sedentary activity (p < 0.001). CONCLUSIONS: Mean oral and nasal Rfilter for all 3 PRs was at, or below, the minimal threshold level for detection of inspiratory resistance (the 58.8-74.5 Pa/l*s-1), which may account for the previously-reported lack of significant subjective or physiological differences when wearing PRs with these low Rfilter. Lowering filtering facepiece respirator Rfilter below 88.2 Pa (measured at 85 l/min constant airflow) may not result in additional subjective or physiological benefit to the wearer. PMID- 26159951 TI - Identification of cross-reactive carbohydrate determinants in subjects reporting work-related respiratory symptoms. AB - INTRODUCTION: The role of cross-reactive carbohydrate determinants (CCDs) in diagnostics of occupational allergy remains unclarified and its clinical relevance is still questioned. The aim of the study was to assess the frequency of positive response to CCDs in the subjects with suspected occupational allergy and the relationship between other diagnostic test results and final diagnosis. MATERIAL AND METHODS: The study group included 201 patients. They underwent clinical examination, skin prick test (SPT) to common and occupational allergens, specific serum immunoglobulin (sIgE) determinations, spirometry and specific inhalation challenge test. Moreover, sIgE to CCDs from bromelain was assessed in all subjects. RESULTS: Occupational respiratory allergy was recognized in 64.3% of CCD-positive and 52.4% of CCD-negative patients. Positive SPT results to common and occupational allergens were found in 64.3% and 35.7% of CCD-positive subjects, respectively. In all subjects with CCDs, the sIgE to grass pollens as well as to occupational allergens were detected. The total IgE level > 100 kU/l was significantly associated with the presence of sIgE to CCDs. CONCLUSIONS: sIgE to CCDs were found in 7% of subjects suspected to suffer from occupational respiratory allergy. The presence of CCDs is not significantly associated with occupational respiratory allergy. It is also not more frequent in subjects reporting work-related respiratory symptoms in whom occupational allergy was not confirmed. The elevated total IgE level was related with CCD positivity. In patients with suspected occupational allergy, the presence of sIgE to CCDs in serum did not indicate the irrelevance of positive sIgE to occupational allergens. PMID- 26159952 TI - Job burnout and engagement among teachers - Worklife areas and personality traits as predictors of relationships with work. AB - INTRODUCTION: The main goal of the present study was to analyze the burnout syndrome due to selected personality traits (based on the Cloninger's psychobiological personality model and positive and negative affectivity) and the degree of mismatch between teachers and their work environment (described in terms of the Model of Worklife Areas). The 2nd goal was to determine if the participants could be classified into different burnout profile groups (clusters) based on their burnout dimension (exhaustion, cynicism and efficacy) scores and whether those groups differed significantly with regard to their personality traits and levels of mismatch between them and the workplace. MATERIAL AND METHODS: Individual and contextual factors responsible for burnout were analyzed in a group of 205 Polish teachers who completed a set of questionnaires: Maslach Burnout Inventory - General Scale, Areas of Worklife Scale, Temperament and Character Inventory, and Positive and Negative Affect Schedule. RESULTS: The hierarchical regression analysis revealed that teachers' efficacy is determined only by personality factors, while exhaustion and cynicism are determined by both individual and organizational variables. The cluster analysis revealed 3 groups (burnout, engaged, ineffective) that varied in the level of all burnout dimensions. Teachers experiencing burnout perceived a higher level of mismatch between themselves and the work environment, compared to the engaged teachers demonstrating better alignment. The engaged teachers were lower on negative affectivity and higher on self-directedness as compared to the burnout group. CONCLUSIONS: The study provided insight into the role of individual factors in the development of teacher burnout and engagement. Negative affectivity could be considered as a predisposing risk factor and self-directedness as a protective factor for burnout. PMID- 26159953 TI - No alterations in diurnal cortisol profiles before and during the treatment in patients with stress-related exhaustion. AB - INTRODUCTION: Several theories have emerged in recent years suggesting that neuroendocrinological alterations, mainly changes in cortisol, could be of importance with respect to the link between chronic stress and disease. This study investigated possible deviations in the diurnal cortisol profiles of patients with clinically diagnosed stress-related exhaustion (exhaustion disorder - ED) compared with healthy controls. MATERIAL AND METHODS: Salivary cortisol samples taken at home in the morning directly after waking up, 30 min later, and in the evening were compared between ED patients (N = 122; 25% men) and healthy controls (N = 98; 44% men). Follow-up measurements were performed after 6 months (79 patients) and 12 months (68 patients) of the treatment. RESULTS: There were no clear differences in diurnal salivary cortisol profiles between the patients and healthy controls. Moreover, salivary cortisol levels and diurnal profiles did not change significantly during the treatment in the patient group. There was some indication of a smaller cortisol awakening response in the male patients compared to the male controls, but the difference appeared to be mainly related to the antidepressant use. CONCLUSIONS: Diurnal salivary cortisol profiles, at least as measured in this study, give a rather poor reflection of the prolonged stress exposure experienced by patients with ED. Such basal salivary cortisol measurements do not seem suitable as biomarkers for stress-related conditions such as ED or burnout, or as an aid to assess the effects of prolonged stress load in a routine clinical practice. PMID- 26159954 TI - Visible fungi growth and dampness assessed using a questionnaire versus airborne fungi, (1->3)-beta-D-glucan and fungal spore concentrations in flats. AB - INTRODUCTION: The study aimed at determination of the usefulness of the subjective assessment of selected signs of fungi growth in flats and microclimate parameters to indicate the actual air contamination with culturable fungi, (1->3) beta-D-glucans and fungal spores. MATERIAL AND METHODS: This analysis covered 22 flats, the inhabitants of which declared in a questionnaire interview the presence of the developed mycelium on solid surfaces in the flat. Air samples for determination of the culturable fungi, (1->3)-beta-D-glucans and (viable and non viable) fungal spores concentrations indoor and outdoor the flats during the heating period were collected. During bioaerosol sampling microclimate parameters were measured. Predictive models for concentrations of the tested biological agents with regard to various ways to assess fungal contamination of air in a flat (on the basis of a questionnaire or a questionnaire and microclimate measurements) were built. RESULTS: The arithmetic means of temperature, relative humidity, CO2 concentration and air flow velocity in the flats were respectively: 20.5 degrees C, 53%, 1431.6 ppm and 0 m/s. The geometric mean concentrations of airborne fungi, (1->3)-beta-D-glucans and fungal spores in these premises amounted to 2.9*102 cfu/m3, 1.6 ng/m3 and 5.7*103 spores/m3, respectively. The subjective assessment of fungi growth signs and microclimate characteristics were moderately useful for evaluation of the actual airborne fungi and (1->3)-beta-D glucan concentrations (maximum percent of explained variance (VE) = 61% and 67%, respectively), and less useful in evaluation of the actual fungal spore concentrations (VE < 29%). In the case of fungi, higher usefulness was indicated of the questionnaire evaluation supported by microclimate measurements (VE = 61.2%), as compared to the evaluation only by means of a questionnaire (VE = 46.9%). CONCLUSIONS: Subjective evaluation of fungi growth signs in flats, separately or combined with microclimate measurements, appeared to be moderately useful for quantitative evaluation of the actual air contamination with fungi and their derivatives, but more extensive studies are needed to strengthen those findings. PMID- 26159955 TI - Maternal waterpipe smoke exposure and the risk of asthma and allergic diseases in childhood: A post hoc analysis. AB - INTRODUCTION: This analysis was conducted with the objective of evaluating association between waterpipe passive smoking exposure and asthma, and allergies among Lebanese children. MATERIAL AND METHODS: Data were taken from a crosssectional study on children from public and private schools. A sample of 22 schools participated in the study, where standardized written core questionnaires were distributed. From 5 to 12-year-old students filled in the questionnaires at home, while 13-14-year-old students filled it in in the class. In total, 5522 children were evaluated for the prevalence of asthma, allergic rhinitis and atopic eczema, and their associated factors, including waterpipe exposure due to parents' smoking. RESULTS: The descriptive results of parental smoking were, as follows: among mothers: 1609 (29%) mothers smoked cigarettes, 385 (7%) smoked waterpipe and 98 (1.8%) smoked both; among fathers: 2449 (44.2%) smoked cigarettes, 573 (10.3%) smoked waterpipe and 197 (3.5%) smoked both. Maternal waterpipe smoking was significantly and moderately associated with allergic diseases (p < 0.001; ORa = 1.71), including probable asthma, rhinitis and dermatitis (p < 0.001 for all). Quite on the opposite, father's waterpipe smoking was not associated with any of the diseases. Parental cigarette smoking demonstrated some positive effects: father's cigarette smoking did not show association with dermatitis or asthma diagnosed by a physician, while mother's cigarette smoking showed a positive association only with probable asthma. Moreover, no interactions between cigarette and waterpipe smoking were observed. CONCLUSIONS: Maternal waterpipe smoking should be regarded as a high risk behavior; however, additional studies are necessary to confirm this finding. PMID- 26159956 TI - A 12-month exercise intervention decreased stress symptoms and increased mental resources among working adults - Results perceived after a 12-month follow-up. AB - INTRODUCTION: This study evaluated the effect of a 12-month physical exercise intervention accompanied by a 12-month followup evaluating stress symptoms (SS), mental resources (MR) and cardiorespiratory fitness (CRF) in healthy, working adults. We hypothesized that the stress symptoms would decrease and mental resources would increase during the intervention and that these results are associated with changes in CRF. MATERIAL AND METHODS: The study group included healthy adults (N = 371). Three hundred thirty eight participants (212 women, 126 men) were allocated in the exercise group and 33 in the control group (17 women and 16 men). For the analysis, the exercise group was divided into subgroups according to the baseline SS and MR. Stress symptoms and MR were measured using the Occupational Stress Questionnaire. RESULTS: During the 12-month exercise intervention, SS decreased by 16% (p < 0.0001), MR increased by 8% (p < 0.0001) and CRF increased by 7% (p < 0.0001) in the exercise group, while no changes occurred in the control group (ANCOVA, p < 0.01). In the exercise group, the results (SS, MR, and CRF) remained improved during the follow-up. There was a positive correlation between the change in SS and the change in CRF (r = 0.19, p < 0.01). In the subgroup having the highest SS at baseline, SS during the intervention decreased most (26%) (ANCOVA, p < 0.0001). CONCLUSIONS: One year physical exercise intervention improved mental well-being among working adults and this was associated with an improvement in cardiorespiratory fitness. The positive changes remained after the 12-month follow-up. PMID- 26159957 TI - Critical ischemia of the fingers in an auto mechanic as a result of occupational exposure. AB - Hypothenar hammer syndrome is a rare cause of ischemic fingers observed mainly in young men smoking cigarettes and it is associated with repeated trauma of the ulnar artery in the area of the hypothenar eminence of the dominant-hand arm, resulting in a deficit of blood supply with the occurrence of hand symptoms typical for chronic and sometimes critical ischemia. Artery injury in this location is most often the result of multiple repetitions of the same activity being mostly the result of occupational exposure. We present a case of a 27-year old car mechanic admitted to the hospital with symptoms of critical ischemia of the fingers III, IV, and V of the right hand, which resolved after conservative treatment. PMID- 26159958 TI - Cardiotoxic effect due to accidental ingestion of an organic solvent. AB - Toxic myocardial injury can be misdiagnosed as a myocardial infarction, resulting in the patient undergoing standard treatment for cardiac rehabilitation. However, such inadequate therapeutic strategies can lead to cardiovascular complications including dilated cardiomyopathy. This study presents a case of a 65-year-old man after accidental ingestion of organic solvents (toluene and xylene), whose condition demonstrated all the criteria for diagnosis of myocardial infarction. The qualitative determinations of the above mentioned volatile organic compounds (VOCs) in whole blood were carried out using a headspace sampling by means of gas chromatography. Cardiac catheterization revealed no specific coronary lesions, only a muscular bridge causing a 30-50% stenosis in the middle of the circumflex branch of the left coronary artery. PMID- 26159959 TI - Preventive echocardiographic examination in athletes and workers - Quadricuspid aortic valve and atrial septal aneurysm in a young basketball player. AB - Ensuring safety of young athletes and employees who perform hard physical work within the scope of their professional duties, with a special focus on prevention of a sudden cardiac death at sports fields or during hard physical work is one of the most important tasks, which demands joint effort of cardiologists and sport physicians or occupational physicians, who qualify patients for a job or a sport discipline. Apart from hypertrophic and arhythmogenic right ventricular cardiomyopathy, coronary anomalies and aortic dissection belong to the most frequent causes of dramatic complications during competitive exercise or work with an increased energy expenditure. Although a detailed medical history and a physical examination combined with 12-lead ECG assessment may significantly improve the safety in competitive sports, adding echocardiography examination gives a detailed and noninvasive insight into the heart morphology and function. Therefore, in our opinion, it should constitute a standard part of the evaluation of candidates for competitive sports. The practice indicates that beyond subjects with severe heart diseases and those classified as normal, there is a group of individuals with abnormalities which should be more closely monitored, but are not contraindications against professional sports or work with an increased energy expenditure. We describe the case of a young female with a diagnosis of rare congenital aortic valve disease, quadricuspid valve, with mild regurgitation and atrial septal aneurysm which was established during transthoracic echocardiography and confirmed and expanded during TEE examination. PMID- 26159960 TI - Negotiation, treatment and consent. PMID- 26159961 TI - Mental health: Would you choose a dental degree? PMID- 26159962 TI - Avoidable student suicides. PMID- 26159963 TI - Few loupes in India. PMID- 26159964 TI - Oral health and nutrition: Aspartame and other materials. PMID- 26159965 TI - Endodontics: To intervene or not to intervene. PMID- 26159966 TI - Stereopsis in dentistry: Dismal sporting skills. PMID- 26159967 TI - Stress: TABOO. A 'practice that is prohibited or restricted by social or religious custom'. PMID- 26159968 TI - A day in the life: Dentist, dancer, fashion guru. PMID- 26159971 TI - New cover series celebrates 80 years of the BDA Museum. PMID- 26159972 TI - One good deed can change a life. PMID- 26159975 TI - Revolution vs status quo? Non-intervention strategy of asymptomatic third molars causes harm. AB - The Faculty of Dental Surgery of the Royal College of Surgeons of England has prompted the National Institute for Health and Care Excellence to urgently re assess the TA1 guidance on extractions of wisdom teeth and highlighted required amendments to the present version in light of published evidence concerning the harm caused by wisdom tooth retention. This article seeks to address the recent concerns relating the increasing frequency of distal-cervical caries in lower second molar teeth when associated with asymptomatic partially erupted mesial or horizontal impacted mandibular third molars. Such acute angle impactions are classified as partially erupted when one of the third molar cusps breached the epithelial attachment of the distal aspect of the second molar, thus prevents the formation of a gingival seal. At its earliest stage the wisdom tooth appears clinically absent or unerupted, yet histologically the architecture of the gingival epithelium has been disrupted allowing ingress of microbes, demineralisation and succeeding cavitation to take place on the distal aspect of the second molar. We hope to highlight the difficulties faced in addressing this growing clinical problem and encourage clinicians to re-evaluate their own caries risk assessment and caries prevention strategy in relation to mesial and horizontal third molar extractions. PMID- 26159976 TI - Rethinking root canal treatment: understanding the difference between preventing and treating endodontic infection. AB - Root canal treatment is a frequently performed procedure aimed to address pulpal and peri-radicular disease. It comprises a number of clinical steps regardless of the initial diagnosis. The emphasis of each step varies according to whether there is a vital pulp (non-infected) or if the pulp system contains necrotic, infected tissue and there is peri-apical pathology. This article aims to discuss the differences in performing root canal treatments on teeth with vital and non vital pulps. The reader should understand the differences between performing a root canal treatment in teeth with vital pulps and those with infected root canal spaces and peri-radicular pathology. PMID- 26159980 TI - Cost effectiveness modelling of a 'watchful monitoring strategy' for impacted third molars vs prophylactic removal under GA: an Australian perspective. AB - OBJECTIVE: To develop a national level cost model of both the direct and indirect costs of hospitalisations for impacted teeth in Australia. This model will then be used to compare a watchful monitoring strategy for impacted third molars versus prophylactic removal under GA, and calculate possible cost savings in the scenario where Australia would adopt guidelines comparable to the UK. METHODS: Western Australian real hospitalisation data for impacted/embedded teeth removal for 2008/2009 were extrapolated into a national, Australian-wide cost distribution model for removal strategy. The components of a watchful monitoring strategy were calculated over a one-year, and 20-year period. Cost estimates for both strategies were then compared. RESULTS: The estimated number of hospitalisations for impacted teeth in Australia in 2008/2009 for the age group 15-34 years was 97,949. The estimated average annual direct cost was $350 million, the indirect cost was $181 million and total cost was $531 million. Individual cost of the watchful monitoring strategy over 20 years was $1,077, with an annual estimated cost of $53. The proposed guidelines would lead to an annual figure of 83,850 individuals avoiding hospitalisation and shifting to watchful monitoring strategy, and an annual reduction of costs ranging between $420-513 million. CONCLUSION: With no evidence to support the prophylactic removal of asymptomatic wisdom teeth, a proposed watchful monitoring strategy is a more cost-effective alternative in the Australian context. PMID- 26159981 TI - Maintaining dental implants--do general dental practitioners have the necessary knowledge? AB - OBJECTIVE: The aim of this study was to understand the opinion of general dental practitioners about the current level of implant education at both undergraduate and postgraduate levels. MATERIALS AND METHODS: A questionnaire was sent to the general dental practitioners working in a group of practices in the West Midlands, UK. The completed responses were analysed. RESULTS: Ninety-one out of 101 dentists responded to the questionnaires (95.6%). Sixty-seven (77%) dentists stated that they learnt only theoretical aspects of dental implants during their undergraduate training. The majority of them stated that the training they received was not adequate. In addition, few barriers in dental implant provision by general dentists were also identified in the survey. The main barriers were risk of failures (56.3%), to avoid complications (65.5%) and the cost of learning (51.7%). The results were correlated to the implant competences set by the regulatory organisations such as General Dental Council and Association of Dental Education Europe. CONCLUSION: The present study confirmed that the current implant education at both undergraduate and postgraduate levels in the UK does not instil confidence to the GDPs to provide and maintain dental implants. PMID- 26159982 TI - Periodontology in the undergraduate curriculum in UK dental schools. AB - INTRODUCTION: In 1980 the British Society of Periodontology published a series of educational goals which have guided periodontal curricula at UK dental schools. Further, a survey of UK dental schools evaluated aspects of teaching and learning in periodontology. The aims of this project were to identify teaching practices and assessments in periodontology and best practice which may be developed in the future. MATERIALS AND METHODS: A questionnaire was sent to dental schools who had participated in the previous survey. The questionnaire sought information on aspects of teaching and learning in periodontology: teaching manpower, curriculum structure, assessment, research opportunities for students and whether implantology is delivered in the undergraduate curriculum. RESULTS: There is consistency between the education providers with respect to teaching and learning in periodontology. Most are developing integrated learning between dental undergraduates and members of the dental team although there are opportunities for further development. Students are expected to have knowledge of complex treatments but are not expected to be competent at undertaking periodontal surgery nor placing and restoring implants. CONCLUSION: The findings confirm that there is considerable consistency between the education providers with respect to aspects of teaching and learning in periodontology. PMID- 26159983 TI - Bodybuilding supplementation and tooth decay. AB - Supplementation is a key component in bodybuilding and is increasingly being used by amateur weight lifters and enthusiasts to build their ideal bodies. Bodybuilding supplements are advertised to provide nutrients needed to help optimise muscle building but they can contain high amounts of sugar. Supplement users are consuming these products, while not being aware of their high sugar content, putting them at a higher risk of developing dental caries. It is important for dental professionals to recognise the increased risk for supplement users and to raise awareness, provide appropriate preventative advice and be knowledgeable of alternative products to help bodybuilders reach their goals, without increasing the risk of dental caries. PMID- 26159995 TI - Dimerization-driven degradation of C. elegans and human E proteins. AB - E proteins are conserved regulators of growth and development. We show that the Caenorhabditis elegans E-protein helix-loop-helix-2 (HLH-2) functions as a homodimer in directing development and function of the anchor cell (AC) of the gonad, the critical organizer of uterine and vulval development. Our structure function analysis of HLH-2 indicates that dimerization drives its degradation in other uterine cells (ventral uterine precursor cells [VUs]) that initially have potential to be the AC. We also provide evidence that this mode of dimerization driven down-regulation can target other basic HLH (bHLH) dimers as well. Remarkably, human E proteins can functionally substitute for C. elegans HLH-2 in regulating AC development and also display dimerization-dependent degradation in VUs. Our results suggest that dimerization-driven regulation of bHLH protein stability may be a conserved mechanism for differential regulation in specific cell contexts. PMID- 26159994 TI - RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. AB - N(6)-methyladenosine (m(6)A) is the most prevalent and internal modification that occurs in the messenger RNAs (mRNA) of most eukaryotes, although its functional relevance remained a mystery for decades. This modification is installed by the m(6)A methylation "writers" and can be reversed by demethylases that serve as "erasers." In this review, we mainly summarize recent progress in the study of the m(6)A mRNA methylation machineries across eukaryotes and discuss their newly uncovered biological functions. The broad roles of m(6)A in regulating cell fates and embryonic development highlight the existence of another layer of epigenetic regulation at the RNA level, where mRNA is subjected to chemical modifications that affect protein expression. PMID- 26159996 TI - H3K36 methylation promotes longevity by enhancing transcriptional fidelity. AB - Epigenetic mechanisms, including histone post-translational modifications, control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging phenomenon of shortened life span, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a life span screen in Saccharomyces cerevisiae that is designed to identify amino acid residues of histones that regulate yeast replicative aging. Our results reveal that lack of sustained histone H3K36 methylation is commensurate with increased cryptic transcription in a subset of genes in old cells and with shorter life span. In contrast, deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes, suppresses cryptic transcript initiation, and extends life span. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to loss of transcriptional precision that is detrimental to life span, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity. PMID- 26159997 TI - Histone H3.3 maintains genome integrity during mammalian development. AB - Histone H3.3 is a highly conserved histone H3 replacement variant in metazoans and has been implicated in many important biological processes, including cell differentiation and reprogramming. Germline and somatic mutations in H3.3 genomic incorporation pathway components or in H3.3 encoding genes have been associated with human congenital diseases and cancers, respectively. However, the role of H3.3 in mammalian development remains unclear. To address this question, we generated H3.3-null mouse models through classical genetic approaches. We found that H3.3 plays an essential role in mouse development. Complete depletion of H3.3 leads to developmental retardation and early embryonic lethality. At the cellular level, H3.3 loss triggers cell cycle suppression and cell death. Surprisingly, H3.3 depletion does not dramatically disrupt gene regulation in the developing embryo. Instead, H3.3 depletion causes dysfunction of heterochromatin structures at telomeres, centromeres, and pericentromeric regions of chromosomes, leading to mitotic defects. The resulting karyotypical abnormalities and DNA damage lead to p53 pathway activation. In summary, our results reveal that an important function of H3.3 is to support chromosomal heterochromatic structures, thus maintaining genome integrity during mammalian development. PMID- 26159998 TI - Chaperoning 5S RNA assembly. AB - In eukaryotes, three of the four ribosomal RNAs (rRNAs)-the 5.8S, 18S, and 25S/28S rRNAs-are processed from a single pre-rRNA transcript and assembled into ribosomes. The fourth rRNA, the 5S rRNA, is transcribed by RNA polymerase III and is assembled into the 5S ribonucleoprotein particle (RNP), containing ribosomal proteins Rpl5/uL18 and Rpl11/uL5, prior to its incorporation into preribosomes. In mammals, the 5S RNP is also a central regulator of the homeostasis of the tumor suppressor p53. The nucleolar localization of the 5S RNP and its assembly into preribosomes are performed by a specialized complex composed of Rpf2 and Rrs1 in yeast or Bxdc1 and hRrs1 in humans. Here we report the structural and functional characterization of the Rpf2-Rrs1 complex alone, in complex with the 5S RNA, and within pre-60S ribosomes. We show that the Rpf2-Rrs1 complex contains a specialized 5S RNA E-loop-binding module, contacts the Rpl5 protein, and also contacts the ribosome assembly factor Rsa4 and the 25S RNA. We propose that the Rpf2-Rrs1 complex establishes a network of interactions that guide the incorporation of the 5S RNP in preribosomes in the initial conformation prior to its rotation to form the central protuberance found in the mature large ribosomal subunit. PMID- 26159999 TI - Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval. AB - AIMS: We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers. METHODS AND RESULTS: All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database. We screened a Danish population-based sample with available whole-exome sequencing data (n = 870) and genotype array data (n = 6161) for putative cLQTS genetic variants. In total, 33 of 1358 variants previously reported to associate with cLQTS were identified. Of these, 10 variants were found in 8 or more individuals. Electrocardiogram results showed normal mean QTc intervals in carriers compared with non-carriers. Syncope data analysis between variant and non-variant carriers showed that 4 of 227 (1.8%) and 95 of 5861 (1.6%) individuals, respectively, had experienced syncope during follow-up (P = 0.80). There was no significant difference in overall mortality rates between carriers [7/217 (3.2%)] and non-carriers [301/6453 (4.7%)] (P = 0.24). CONCLUSION: We present QTc data and register data, indicating that 26 cLQTS-associated variants neither had any effect on the QTc intervals nor on syncope propensity or overall mortality. Based on the frequency of individual gene variants, we suggest that the 10 variants frequently identified, assumed to relate to cLQTS, are less likely to associate with a dominant monogenic form of the disease. PMID- 26160000 TI - Abdominal aortic aneurysm and lumbar plexus palsy. PMID- 26160002 TI - Calcification of the mitral valve complicated by embolization and subsequent ischemic stroke with haemorrhagic transformation. PMID- 26160001 TI - Canopy 2 attenuates the transition from compensatory hypertrophy to dilated heart failure in hypertrophic cardiomyopathy. AB - AIMS: A mismatch between adequate angiogenesis and overgrowth of myocytes may be a critical mechanism controlling the transition from adaptive hypertrophy to heart failure. Canopy 2 (CNPY2) was recently identified as a secreted, HIF-1alpha regulated angiogenic growth factor. As angiogenic factors play important roles in the development of myocardial hypertrophy, we investigated the role of CNPY2 in molecular and functional changes during development of chronic heart failure using cardiac-specific transgenic (TG) mice that overexpress human CNPY2. METHODS AND RESULTS: We generated TG mice that constitutively express CNPY2 in the myocardium. Cardiomyopathy was induced in TG and wild-type (WT) mice by transverse aortic constriction (TAC). WT mice developed significant ventricular hypertrophy at 4 weeks and severe dilatation and heart failure at 12 weeks after TAC. However, TG mice preserved much better cardiac structure and function, with less severe ventricular dilatation and markedly reduced cardiac apoptosis and fibrosis following TAC. Excess CNPY2 in TG mice prevented significant loss of vasculature up to 12 weeks after TAC injury, resulting in a better local myocardial environment that facilitated myocyte survival and prevented excessive matrix remodelling compared with WT mice. TG mice had less accumulation of endogenous tumor suppressor p53 after TAC, indicating intrinsic activation of the p53-mediated repression of HIF-1alpha, and Cnpy2 was diminished in TG mice compared with WT controls. CONCLUSION: Our study showed a correlation between downregulation of endogenous mouse Cnpy2 and p53-mediated HIF-1alpha inhibition during late-stage hypertrophic development. Additional CNPY2 attenuated the transition from compensatory hypertrophic response to maladaptive ventricular dilatation and heart failure. PMID- 26160003 TI - Plant reproductive traits mediate tritrophic feedback effects within an obligate brood-site pollination mutualism. AB - Plants, herbivores and parasitoids affect each other directly and indirectly; however, feedback effects mediated by host plant traits have rarely been demonstrated in these tritrophic interactions. Brood-site pollination mutualisms (e.g. those involving figs and fig wasps) represent specialised tritrophic communities where the progeny of mutualistic pollinators and of non-mutualistic gallers (both herbivores) together with that of their parasitoids develop within enclosed inflorescences called syconia (hence termed brood-sites or microcosms). Plant reproductive phenology (which affects temporal brood-site availability) and inflorescence size (representing brood-site size) are plant traits that could affect reproductive resources, and hence relationships between trees, pollinators and non-pollinating wasps. Analysing wasp and seed contents of syconia, we examined direct, indirect, trophic and non-trophic relationships within the interaction web of the fig-fig wasp community of Ficus racemosa in the context of brood site size and availability. We demonstrate that in addition to direct resource competition and predator-prey (host-parasitoid) interactions, these communities display exploitative or apparent competition and trait-mediated indirect interactions. Inflorescence size and plant reproductive phenology impacted plant-herbivore and plant-parasitoid associations. These plant traits also influenced herbivore-herbivore and herbivore-parasitoid relationships via indirect effects. Most importantly, we found a reciprocal effect between within tree reproductive asynchrony and fig wasp progeny abundances per syconium that drives a positive feedback cycle within the system. The impact of a multitrophic feedback cycle within a community built around a mutualistic core highlights the need for a holistic view of plant-herbivore-parasitoid interactions in the community ecology of mutualisms. PMID- 26160004 TI - [Malignant head and neck melanoma : Part 1: Diagnosis and histological particularities]. AB - About 15% of all cutaneous melanomas develop in the head and neck region. Mucosal melanomas are rare and represent only 1% of all melanomas, however, most frequently, these are located in the nose, the paranasal sinuses and the oral cavity. Visual diagnosis and reflected-light microscopy are relevant for the evaluation of melanoma-suspect lesions. Histological investigation of resected tumors need special skills of the histopathologist and includes in case of high risk tumors investigations of mutations in the tumor tissue concerning NRAS, BRAF and KIT. The risk of lymphatic or hematogeneous spread rises with increasing tumor thickness and the presence of further prognostic risk factors such as ulceration of the primary tumor or the presence of mitoses within the tumor. PMID- 26160005 TI - [Head and neck hamartomas: 10 years of experience at the Charite--University Medical Center Berlin]. AB - BACKGROUND: Head and neck tumors are rare entities in neonates. Hamartomas are benign congenital neoplasms. To date, there is a lack of sufficient epidemiological data concerning hamartomas in the field of otorhinolaryngology. MATERIALS AND METHODS: We retrospectively analyzed experiences at the Charite over the past 10 years in an ICD-10-based manner. Our otorhinolaryngology department maintains close cooperation with the level 1 perinatal center on our campus. RESULTS: The authors identified 3 patients suffering from fibrous hamartomas. This corresponds to an incidence of 2-3/30,000 newborns. The clinical aspects and courses are described in detail. Experiences with the management of hamartomas obstructing the upper aerodigestive tract are described. CONCLUSION: Head and neck hamartomas are very rare malformations. They possess the ability to cause otorhinolaryngological emergencies in newborns. Interdisciplinary management and histological assessment are mandatory. Anmerkung. PMID- 26160006 TI - Rule-based versus probabilistic selection for active surveillance using three definitions of insignificant prostate cancer. AB - PURPOSE: To study whether probabilistic selection by the use of a nomogram could improve patient selection for active surveillance (AS) compared to the various sets of rule-based AS inclusion criteria currently used. METHODS: We studied Dutch and Swedish patients participating in the European Randomized study of Screening for Prostate Cancer (ERSPC). We explored which men who were initially diagnosed with cT1-2, Gleason 6 (Gleason pattern <=3 + 3) had histopathological indolent PCa at RP [defined as pT2, Gleason pattern <=3 and tumour volume (TV) <=0.5 or TV <= 1.3 ml, and TV no part of criteria (NoTV)]. Rule-based selection was according to the Prostate cancer Research International: Active Surveillance (PRIAS), Klotz, and Johns Hopkins criteria. An existing nomogram to define probability-based selection for AS was refitted for the TV1.3 and NoTV indolent PCa definitions. RESULTS: 619 of 864 men undergoing RP had cT1-2, Gleason 6 disease at diagnosis and were analysed. Median follow-up was 8.9 years. 229 (37%), 356 (58%), and 410 (66%) fulfilled the TV0.5, TV1.3, and NoTV indolent PCa criteria at RP. Discriminating between indolent and significant disease according to area under the curve (AUC) was: TV0.5: 0.658 (PRIAS), 0.523 (Klotz), 0.642 (Hopkins), 0.685 (nomogram). TV1.3: 0.630 (PRIAS), 0.550 (Klotz), 0.615 (Hopkins), 0.646 (nomogram). NoTV: 0.603 (PRIAS), 0.530 (Klotz), 0.589 (Hopkins), 0.608 (nomogram). CONCLUSIONS: The performance of a nomogram, the Johns Hopkins, and PRIAS rule-based criteria are comparable. Because the nomogram allows individual trade-offs, it could be a good alternative to rigid rule-based criteria. PMID- 26160007 TI - Identifying Orbital Angular Momentum of Vectorial Vortices with Pancharatnam Phase and Stokes Parameters. AB - In this work, an explicit formula is deduced for identifying the orbital angular moment (OAM) of vectorial vortex with space-variant state of polarization (SOP). Different to scalar vortex, the OAM of vectorial vortex can be attributed to two parts: 1. the azimuthal gradient of Pancharatnam phase; 2. the product between the azimuthal gradient of orientation angle of SOP and relevant solid angle on the Poincare sphere. With our formula, a geometrical description for OAM of light beams can be achieved under the framework of the traditional Poincare sphere. Numerical simulations for two types of vectorial vortices have been carried on to confirm our presented formula as well as demonstrate the geometrical description of OAM. Furthermore, this work would pave the way for precise characterization of OAM charge of vectorial vortices. PMID- 26160008 TI - High Affinity Host-Guest FRET Pair for Single-Vesicle Content-Mixing Assay: Observation of Flickering Fusion Events. AB - Fluorescence-based single-vesicle fusion assays provide a powerful method for studying mechanisms underlying complex biological processes of SNARE (soluble N ethylmaleimide-sensitive factor attachment protein receptor)-mediated vesicle fusion and neurotransmitter release. A crucial element of these assays is the ability of the fluorescent probe(s) to reliably detect key intermediate events of fusion pore opening and content release/mixing. Here, we report a new, reliable, and efficient single-vesicle content-mixing assay using a high affinity, fluorophore tagged host-guest pair, cucurbit[7]uril-Cy3 and adamantane-Cy5 as a fluorescence resonance energy transfer (FRET) pair. The power of these probes is demonstrated by the first successful observation of flickering dynamics of the fusion pore by in vitro assay using neuronal SNARE-reconstituted vesicles. PMID- 26160009 TI - Bacillus amyloliquefaciens subsp. plantarum GR53, a potent biocontrol agent resists Rhizoctonia disease on Chinese cabbage through hormonal and antioxidants regulation. AB - The fungus Rhizoctonia solani is one of the causal agents of numerous diseases that affect crop growth and yield. The aim of this present investigation was to identify a biocontrol agent that acts against R. solani and to determine the agent's protective effect through phytohormones and antioxidant regulation in experimentally infected Chinese cabbage plants. Four rhizospheric soil bacterial isolates GR53, GR169, GR786, and GR320 were tested for their antagonistic activity against R. solani. Among these isolates, GR53 significantly suppressed fungal growth. GR53 was identified as Bacillus amyloliquefaciens subsp. plantarum by phylogenetic analysis of the 16S rDNA sequence. The biocontrol activity of B. amyloliquefaciens subsp. plantarum GR53 was tested in Chinese cabbage plants under controlled conditions. Results showed that R. solani inhibited plant growth (length, width, fresh and dry weight of leaves) by reducing chlorophyll and total phenolic content, as well as by increasing the levels of salicylic acid, jasmonic acid, abscisic acid, and DPPH scavenging activity. By regulating the levels of these compounds, the co-inoculation of B. amyloliquefaciens subsp. plantarum GR53 heightened induced systemic resistance in infected Chinese cabbage, effectively mitigating R. solani-induced damaging effects and improving plant growth. The results obtained from this study suggest that B. amyloliquefaciens subsp. plantarum GR53 is an effective biocontrol agent to prevent the damage caused by R. solani in Chinese cabbage plants. PMID- 26160011 TI - Benzene at 1GHz. Magnetic field-induced fine structure. AB - The deuterium NMR spectrum of benzene-d6 in a high field spectrometer (1GHz protons) exhibits a magnetic field-induced deuterium quadrupolar splitting Deltanu. The magnitude of Deltanu observed for the central resonance is smaller than that observed for the (13)C satellite doublets Deltanu'. This difference, Delta(Deltanu)=Deltanu'-Deltanu, is due to unresolved fine structure contributions to the respective resonances. We determine the origins of and simulate this difference, and report pulse sequences that exploit the connectivity of the peaks in the (13)C and (2)H spectra to determine the relative signs of the indirect coupling, JCD, and Deltanu. The positive sign found for Deltanu is consonant with the magnetic field biasing of an isolated benzene molecule-the magnetic energy of the aromatic ring is lowest for configurations where the C6 axis is normal to the field. In the neat liquid the magnitude of Deltanu is decreased by the pair correlations in this prototypical molecular liquid. PMID- 26160010 TI - Physiological adaptations of yeasts living in cold environments and their potential applications. AB - Yeasts, widely distributed across the Earth, have successfully colonized cold environments despite their adverse conditions for life. Lower eukaryotes play important ecological roles, contributing to nutrient recycling and organic matter mineralization. Yeasts have developed physiological adaptations to optimize their metabolism in low-temperature environments, which affect the rates of biochemical reactions and membrane fluidity. Decreased saturation of fatty acids helps maintain membrane fluidity at low temperatures and the production of compounds that inhibit ice crystallization, such as antifreeze proteins, helps microorganisms survive at temperatures around the freezing point of water. Furthermore, the production of hydrolytic extracellular enzymes active at low temperatures allows consumption of available carbon sources. Beyond their ecological importance, interest in psychrophilic yeasts has increased because of their biotechnological potential and industrial uses. Long-chain polyunsaturated fatty acids have beneficial effects on human health, and antifreeze proteins are attractive for food industries to maintain texture in food preserved at low temperatures. Furthermore, extracellular cold-active enzymes display unusual substrate specificities with higher catalytic efficiency at low temperatures than their mesophilic counterparts, making them attractive for industrial processes requiring high enzymatic activity at low temperatures. In this minireview, we describe the physiological adaptations of several psychrophilic yeasts and their possible biotechnological applications. PMID- 26160012 TI - Extending long-range heteronuclear NMR connectivities by HSQMBC-COSY and HSQMBC TOCSY experiments. AB - The detection of long-range heteronuclear correlations presenting J(CH) coupling values smaller than 1-2Hz is a challenge in the structural analysis of small molecules and natural products. HSQMBC-COSY and HSQMBC-TOCSY pulse schemes are evaluated as complementary NMR methods to standard HMBC/HSQMBC experiments. Incorporation of an additional J(HH) transfer step in the basic HSQMBC pulse scheme can favor the sensitive observation of traditionally missing or very weak correlations and, in addition, facilitates the detection of a significant number of still longer-range connectivities to both protonated and non-protonated carbons under optimum sensitivity conditions. A comparative (1)H-(13)C study is performed using strychnine as a model compound and several examples are also provided including (1)H-(15)N applications. PMID- 26160013 TI - Cellular FLICE-Inhibitory Protein Regulates Tissue Homeostasis. AB - Cellular FLICE-inhibitory protein (cFLIP) is structurally related to caspase-8, but lacks its protease activity. Cflip gene encodes several splicing variants including short form (cFLIPs) and long form (cFLIPL). cFLIPL is composed of two death effector domains at the N terminus and a C-terminal caspase-like domain, and cFLIPs lacks the caspase-like domain. Our studies reveal that cFLIP plays a central role in NF-kappaB-dependent survival signals that control apoptosis and programmed necrosis. Germline deletion of Cflip results in embryonic lethality due to enhanced apoptosis and programmed necrosis; however, the combined deletion of the death-signaling regulators, Fadd and Ripk3, prevents embryonic lethality in Cflip-deficient mice. Moreover, tissue-specific deletion of Cflip reveals cFLIP as a crucial regulator that maintains tissue homeostasis of immune cells, hepatocytes, intestinal epithelial cells, and epidermal cells by preventing apoptosis and programmed necrosis. PMID- 26160014 TI - Haploidentical Haematopoietic Stem Cell Transplantation: Role of NK Cells and Effect of Cytomegalovirus Infections. AB - Natural killer cells play an important role in the immune responses against cancer and viral infections. In addition, NK cells have been shown to exert a key role in haploidentical hematopoietic stem cell (HSC) transplantation for the therapy of high-risk leukemias. The anti-leukemia effect is mostly related to the presence of "alloreactive" NK cells, i.e., mature KIR(+) NK cells that express inhibitory KIR mismatched with HLA class I (KIR-L) of the patient. In addition, an important role is played by certain activating KIR (primarily, but not only, KIR2DS1) upon interaction with their HLA class I ligand (C2 alleles). In general, the presence of activating KIR correlates with a better prognosis. Beside the infusion of "pure" CD34(+) cells, a novel protocol has been recently developed in which depletion of alphabeta T cells and CD19(+) B cells makes it possible to infuse into the patient, together with donor CD34(+) HSCs, important effector cells including mature PB NK cells and gammadelta T cells. Recent studies revealed that cytomegalovirus (CMV) infection/reactivation may induce rapid NK cell maturation and greatly influence the NK receptor repertoire. The remarkable expansion of a subset expressing the activating receptor NKG2C, together with a more efficient virus-specific effector response after rechallenge with CMV (i.e., antigen specificity), and the longevity of the expanded population are all features consistent with an adaptive type of response and support the notion of a memory-like activity of NK cells. PMID- 26160015 TI - Rapid optimization of labeled ubiquitinated peptides for monitoring deubiquitinases activities. AB - Studying and targeting deubiquitinases is of high importance due to their various roles in cellular processes and involvement in diseases such as cancer. The recent development of unique probes and reagents using chemical synthesis of proteins became very instrumental in supporting these efforts. Here, we present a protein synthetic approach that enables the rapid synthesis of differently modified labeled-ubiquitinated peptides to facilitate rapid optimization of deubiquitinase substrates. PMID- 26160016 TI - Amino-Terminal proB-Type Natriuretic Peptide Levels in the Umbilical Cord Blood of Neonates Differ According to the Type of Prenatally Diagnosed Congenital Heart Disease. AB - The aim of this study was to investigate differences in amino-terminal proB-type natriuretic peptide (NT-proBNP) levels in the cord blood of neonates according to the type of congenital heart disease (CHD) and to evaluate the usefulness of NT proBNP as a prognostic marker. We included 76 neonates with prenatally diagnosed CHD and 45 controls without CHD. Neonates were classified into five groups based on echocardiographic findings. The levels of NT-proBNP in the cord blood were examined and analyzed according to the neonatal outcomes. The levels of NT-proBNP were significantly elevated in the cord blood of neonates with CHD compared with that in the cord blood of controls. The levels of NT-proBNP in the group with right ventricular outflow tract obstruction without a ventricular septal defect were significantly increased compared to that in the other groups. The neonates that required acute surgical correction had higher levels of NT-proBNP in the cord blood, though they were not statistically significant. Meanwhile, NT-proBNP levels in the cord blood of neonates with functional single ventricle were significantly higher than that in the cord blood of those with functional biventricles. Significant differences in the levels of NT-proBNP between survivors and nonsurvivors were observed within 1 year of birth. In this study, we found that the levels of NT-proBNP in the cord blood of neonates with CHD were higher than the levels in controls. This finding was striking in the group with right ventricular outflow tract obstruction, and it was associated with surgery for functional single ventricle and 1-year survival. PMID- 26160017 TI - Neuroglobin Plays a Protective Role in Arsenite-Induced Cytotoxicity by Inhibition of Cdc42 and Rac1GTPases in Rat Cerebellar Granule Neurons. AB - BACKGROUND AND AIMS: We have previously shown that neuroglobin (Ngb) expression can be regulated by sodium arsenite (NaAsO2) exposure in rat cerebellar granule neurons (CGNs). However, the precise molecular mechanisms of Ngb action are largely unknown. Ras homolog (Rho) guanosine triphosphatases (Rho GTPases) are involved in the regulation of a number of cellular processes, including cell cytotoxicity. It has been reported that Ngb can act as a guanine nucleotide dissociation inhibitior (GDI) role to inactivate Rho GTPases. Therefore, we investigated Rho GTPases activation induced by NaAsO2 exposure in rat CGNs and effects of Rho GTPases activation on the cells. We also investigated the role of Ngb in this process. METHODS: Primary cultures of CGNs were prepared from 7-day old Wistar rat pups. The cytotoxic effects of NaAsO2 on CGNs were evaluated using the Cell Counting Kit-8 assay and TUNEL staining. RNA interference technology was used to silence Ngb, and the subsequent effects were evaluated by quantitative RT PCR and Western blot. Cdc42 and Rac1 activation were measured by pull-down assay and Western blot. RESULTS: NaAsO2 induced cytotoxicity in rat CGNs, increased GTP bound form of Cdc42 and Rac1 GTPases in the cells. Furthermore, inhibition of Cdc42 or Rac1 activity using the inhibitor ZCL278 or NSC23766 decreased apoptosis and increased cell viability in the cells exposed to NaAsO2. Using siRNA-mediated knockdown, we show that NaAsO2-induced cytotoxicity was exacerbated, activation of Cdc42 (GTP-Cdc42) and Rac1 (GTP-Rac1) was increased in Ngb RNA silencing cells. CONCLUSIONS: cytotoxic effects of NaAsO2 on rat CGNs is induced at least partly by Cdc42 and Rac1 activation, and Ngb can inhibit Cdc42 and Rac1 activation to play protective role in rat CGNs exposed to NaAsO2. PMID- 26160018 TI - Human Papillomavirus Positivity in Women Undergoing Intrauterine Insemination Has a Negative Effect on Pregnancy Rates. AB - BACKGROUND: Sexually transmitted infections are a major cause of infertility. Human papillomavirus (HPV) infection is one of the most common viral infections of the female genital tract. Only a limited number of studies have investigated the influence of HPV on fertility and its impact remains controversial. OBJECTIVE: We investigated the relationship between cervical HPV infection and pregnancy outcome after intrauterine insemination (IUI). Since other sexually transmitted infections could also influence outcome, we also analyzed the influence of Trichomonas vaginalis (TV) and Chlamydia trachomatis (CT) on pregnancy outcome. METHODS: We performed a retrospective analysis of 590 women who underwent 1,529 IUI cycles at AML between 2010 and 2014. Positivity of 18 different HPV types (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68) and TV was assessed by PCR in cervical cytology specimens. CT status was ascertained by detection of IgA/IgG antibodies on serum samples or by PCR on cervical swabs. RESULTS: The HPV prevalence per IUI cycle was 11.0 and 6.9% for CT; none of the women tested positive for TV. HPV-positive women were six times less likely to become pregnant after IUI (1.87 vs. 11.36%; p = 0.0041). There was no significant difference in pregnancy rates between women with or without a history of CT (8.51 vs. 11.10%; p > 0.05). CONCLUSION: Detection of HPV is associated with a negative IUI outcome. PMID- 26160019 TI - Attention in Older Adults: A Normative Study of the Integrated Visual and Auditory Continuous Performance Test for Persons Aged 70 Years. AB - OBJECTIVE: Our objective was to present normative data from 70-year-olds on the Integrated Visual and Auditory Continuous Performance Test (IVA), a computerized measure of attention and response control. METHOD: 640 participants (330 men and 310 women), all aged 70 years, completed the IVA, as well as the Mini-Mental State Examination and the Geriatric Depression Scale. RESULTS: Data were stratified by education and gender. Education differences were found in 11 of 22 IVA scales. Minor gender differences were found in six scales for the high education group, and two scales for the low-education group. Comparisons of healthy participants and participants with stroke, myocardial infarction, or diabetes showed only minor differences. Correlations among IVA scales were strong (all r > .34, p < .001), and those with the widely used Mini-Mental State Examination were weaker (all r < .21, p < .05). Skewed distributions of normative data from primary IVA scales measuring response inhibition (Prudence) and inattention (Vigilance) represent a weakness of this test. CONCLUSIONS: This study provides IVA norms for 70-year-olds stratified by education and gender, increasing the usability of this instrument when testing persons near this age. The data presented here show some major differences from original IVA norms, and explanations for these differences are discussed. Explanations include the broad age-range used in the original IVA norms (66-99 years of age) and the passage of 15 years since the original norms were collected. PMID- 26160020 TI - Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5 trimethoxybenzenes. AB - This study reports the synthesis of a series of heteroaroyl-2-hydroxy-3,4,5 trimethoxybenzenes, which are potent antitubulin agents. Compound 13, (2-hydroxy 3,4,5-trimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)-methanone exhibits marked antiproliferative activity against KB and MKN45 cells with IC50 values of 8.8 and 10.5 nM, respectively, binds strongly to the colchicine binding site and leads to inhibition of tubulin polymerization. It also behaves as a vascular disrupting agent which suppresses the formation of capillaries. The C2-OH group in the A ring of this compound not only retains the biological activity but has valuable physicochemical properties. PMID- 26160021 TI - Evaluation Study for an ISO 13606 Archetype Based Medical Data Visualization Method. AB - The objective of this evaluation study is to assess a method for standard based medical data visualization. The method allows flexible and customizable visualization for ISO 13606 archetype based medical data. The chosen evaluation concept is based the Guideline for Good Evaluation Practice in Health Informatics (GEP-HI). The stages of the study were identified. Each stage got a detailed description. We also identified the participants and their required qualifications and responsibilities. The evaluation location was described in details. The evaluation metrics were defined. The questionnaires for doctors, patients and experts were developed to fulfill the requirements of the evaluation study. The study was performed in Tomsk, Russia. 30 patients and 5 doctors participated in the study. The overall performance of the users reached the expert level by the end of the study. Patients as well as medical staff stated in their comments that the usability of the system was high, and they preferred it to the previously used paper-based and computer based systems. This was also shown by the high level of satisfaction measured within our study. The visualization approach, integrated into the electronic health record, was well accepted in our pilot setting with high usability scores from patients and doctors alike. The results showed the efficiency for both modeling and visualization part of the system. PMID- 26160022 TI - Aging and the subjective experience of time. AB - BACKGROUND: The subjective experience of time involves several, not yet identified, mechanisms. Many cognitive and emotional factors, such as attention, memory and subjective mental states can influence time estimation. AIMS: We aimed to assess the subjective experience of time and its relationships with cognitive and emotional characteristics in the elderly. METHOD: Forty-nine non-demented patients hospitalized for orthopedic rehabilitation underwent an 'ecological' evaluation tool, the semi-structured QUEstionnaire for the Subjective experience of Time (QUEST) requiring retrospective and prospective judgements on self relevant time intervals. All patients completed tests to assess general cognitive functioning and two questionnaires to evaluate emotional state. RESULTS: Results showed that accuracy in time estimation did not differ in young-old vs. old-old individuals: both groups performed better on prospective than on retrospective items and on highly than on poorly self-relevant items. Multiple regression analysis showed that performance on QUEST was significantly related to depression and hospitalization duration, but not to age, education, or neuropsychological scores. CONCLUSIONS: The influence of the emotional state is consistent with theories postulating that the "sense of time" is emergent from emotional and visceral states. PMID- 26160023 TI - A Set of Cytogenetic Markers Allows the Precise Identification of All A-Genome Chromosomes in Diploid and Polyploid Wheat. AB - Karyotypes of 3 diploid wheat species containing different variants of the A genome, Triticum boeoticum (A(b)), T. monococcum (A(b)), and T. urartu (A(u)), were examined using C-banding and FISH with DNA probes representing 5S and 45S rDNA families, the microsatellite sequences GAAn and GTTn, the already known satellite sequences pSc119.2, Spelt52, Fat, pAs1, and pTa535, and a newly identified repeat called Aesp_SAT86. The C-banding patterns of the 3 species in general were similar; differences were observed in chromosomes 4A and 6A. Besides 2 major 45S rDNA loci on chromosomes 1A and 5A, 2 minor polymorphic NORs were observed in the terminal part of 5AL and in the distal part of 6AS in all species. An additional minor locus was found in the distal part of 7A(b)L of T. boeoticum and T. monococcum, but not in T. urartu. Two 5S rDNA loci were observed in 1AS and 5AS. The pTa535 probe displayed species- and chromosome-specific hybridization patterns, allowing complete chromosome identification and species discrimination. The distribution of pTa535 on the A(u)-genome chromosomes was more similar to that on the A-genome chromosomes of T. dicoccoides and T. araraticum, thus confirming the origin of these genomes from T. urartu. The probe pAs1 allowed the identification of 4 chromosomes of T. urartu and 2 of T. boeoticum or T. monococcum. The Aesp_SAT86-derived patterns were polymorphic; main clusters were observed on chromosomes 1A(u )and 3A(u) of T. urartu and chromosomes 3A(b) and 6A(b) of T. boeoticum. Thus, a set of probes, pTa535, pAs1, GAAn and GTTn, pTa71, pTa794, and Aesp_SAT86, proved to be most informative for the analysis of A-genomes in diploid and polyploid wheat species. PMID- 26160025 TI - Time use clusters in children and their associations with sociodemographic factors. AB - BACKGROUND: Understanding patterns of time use of children is helpful in developing target-tailored intervention. The purpose of this study was to investigate the clustering of sedentary behaviours and physical activity in Chinese children and to examine the associations between sociodemographic factors and the time use clusters. METHODS: Cluster analysis was conducted among 1013 Chinese children aged 9-13 years (49.5% boys) recruited in a cross-sectional survey study. Physical activity and sedentary behaviours were assessed using a validated questionnaire. Differences in sociodemographic variables were compared across the clusters. RESULTS: Five clusters were identified for boys and girls, respectively. For boys, the five clusters were labelled 'Actives' (9.1%), 'Inactives' (59.4%), 'Sedentary homeworkers' (4.7%), 'Sedentary TV viewers' (16.6%) and 'Sedentary games players' (10.2%). For girls, they were labelled 'Actives' (11.9%), 'Uninvolved inactives' (39.6%), 'Sedentary homeworkers' (11.3%), 'Sedentary TV viewers' (8.5%) and 'Sedentary Games players' (28.8%). Only parental education was found to differ across the five clusters in boys. CONCLUSIONS: The findings demonstrated that sedentariness in youth is multidimensional, and it could not be accurately represented by singular behaviour. There is a potential need when designing specific interventions to reduce a group of sedentary behaviours to tailor these interventions for specific clusters. PMID- 26160024 TI - Systematic review of adverse health outcomes associated with high serum or red blood cell folate concentrations. AB - BACKGROUND: To examine the relationship between reported high serum or red blood cell (RBC) folate status and adverse health outcomes. METHODS: We systematically searched PubMed/Medline and EMBASE (to May 2013), with no limits by study type, country or population, to identify studies reporting high folate concentrations in association with adverse health outcomes. Two reviewers screened studies and extracted data. Study quality was assessed. RESULTS: We included 51 articles, representing 46 studies and 71 847 participants. Quantiles were used by 96% of studies to identify high folate concentrations. Eighty-three percent of serum folate and 50% of RBC folate studies reported a high folate cutoff that corresponded with a clinically normal concentration. Increasing values of reported high folate concentration did not demonstrate a consistent association with risk of adverse health outcomes. Overall, reported high folate concentrations appeared to be associated with a decreased risk of adverse health outcomes, though substantial methodological heterogeneity precluded complex analyses. CONCLUSIONS: Our interpretation was complicated by methodological variability. High folate cutoffs varied and often corresponded with normal or desirable blood concentrations. In general, a negative association appeared to exist between reported high folate status and adverse health outcomes. Consistent methods and definitions are needed to examine high folate status and ultimately inform public health interventions. PMID- 26160026 TI - Spikes not slots: noise in neural populations limits working memory. AB - This opinion article argues that noise (randomness) in neural activity is the limiting factor in visual working memory (WM), determining how accurately we can maintain stable internal representations of external stimuli. Sharing of a fixed amount of neural activity between items in memory explains why WM can be successfully described as a continuous resource. This contrasts with the popular conception of WM as comprising a limited number of memory slots, each holding a representation of one stimulus - I argue that this view is challenged by computational theory and the latest neurophysiological evidence. PMID- 26160027 TI - Contrasting network and modular perspectives on inhibitory control. AB - A prominent theory proposes that the right inferior frontal cortex of the human brain houses a dedicated region for motor response inhibition. However, there is growing evidence to support the view that this inhibitory control hypothesis is incorrect. Here, we discuss evidence in favour of our alternative hypothesis, which states that response inhibition is one example of a broader class of control processes that are supported by the same set of frontoparietal networks. These domain-general networks exert control by modulating local lateral inhibition processes, which occur ubiquitously throughout the cortex. We propose that to fully understand the neural basis of behavioural control requires a more holistic approach that considers how common network mechanisms support diverse cognitive processes. PMID- 26160028 TI - Fatigue of Nitinol: The state-of-the-art and ongoing challenges. AB - Nitinol, a nearly equiatomic alloy of nickel and titanium, has been considered for a wide range of applications including medical and dental devices and implants as well as aerospace and automotive components and structures. The realistic loading condition in many of these applications is cyclic; therefore, fatigue is often the main failure mode for such components and structures. The fatigue behavior of Nitinol involves many more complexities compared with traditional metal alloys arising from its uniqueness in material properties such as superelasticity and shape memory effects. In this paper, a review of the present state-of-the-art on the fatigue behavior of superelastic Nitinol is presented. Various aspects of fatigue of Nitinol are discussed and microstructural effects are explained. Effects of material preparation and testing conditions are also reviewed. Finally, several conclusions are made and recommendations for future works are offered. PMID- 26160029 TI - Management of Anesthesia in Adult and Pediatric Mastocytosis: A Study of the Spanish Network on Mastocytosis (REMA) Based on 726 Anesthetic Procedures. AB - BACKGROUND: The role of anesthesia as an elicitor of mast cell (MC) mediator release symptoms in mastocytosis is poorly investigated. OBJECTIVE: To determine the frequency and type of MC mediator release symptoms during anesthetic procedures in mastocytosis patients. METHODS: Medical records were reviewed regarding the anesthetic techniques for 501 mastocytosis patients (459 adults and 42 children; 95 and 5% with systemic involvement, respectively) who were subjected to 676 and 50 anesthetic techniques, respectively. General, sedation, epidural, and local anesthetic techniques were used in 66 (10%), 67 (10%), 76 (11%), and 515 (76%) adult patients and in 24 (48%), 8 (16%), 2 (4%), and 25 (50%) pediatric patients. RESULTS: The frequency of perioperative MC mediator related symptoms and anaphylaxis was 2 and 0.4% in the adult series and 4 and 2% among children. In the adult series, this frequency was significantly higher in patients who previously presented with anaphylaxis (p = 0.03), underwent major surgeries (p < 0.001) and general anesthesia (p = 0.02), and were not given prophylactic antimediator therapy (PAT) 1 h before the anesthesia (H1/H2 antihistamines and benzodiacepines; p = 0.002).Hypersensitivity and/or allergy to the involved drugs and latex allergy were ruled out in all but one symptomatic case; when PAT was given and sedation was added, some cases later tolerated the same anesthetic drugs. CONCLUSION: The frequency of perioperative anaphylaxis appears to be higher in mastocytosis patients than in the general population. Mastocytosis should not be a contraindication for anesthesia since PAT and adequate anesthetic management using the drugs with the safest profile appears to be effective in preventing/controlling MC mediator-associated symptoms. PMID- 26160030 TI - Audiometric Results of Open Cavity Tympanomastoidectomy in Advanced Attic Cholesteatoma. AB - In this retrospective study, we evaluated the audiometric results after using the retrograde mastoidectomy technique with open mastoid cavity for the removal of extended attic cholesteatomas. The described technique was used for cholesteatoma removal in 168 adult patients with an average follow-up time of 12 months. Due to cholesteatoma extension far into the mastoid, the disease was eradicated by the canal wall down (CWD) technique with the creation of an open mastoid cavity. Primary surgery was carried out in 47% of ears, with the remaining 53% representing revision surgery. In all cases, a classical CWD with an open mastoid cavity and partial obliteration with cartilage was created. A dry ear was achieved in 94% of cases. A postoperative air-bone gap <= 20 dB was achieved in 42.9% of the operated ears. 9.3% (n = 15) of the operated ears showed a postoperative air-bone gap > 30 dB. Important factors leading to significantly better hearing restoration were an intact malleus, the use of alloplastic titanium prostheses and primary surgery. Although most cholesteatomas nowadays can be eradicated with the canal wall up technique, in far advanced cholesteatomas, the CWD technique can be applied with acceptable postoperative hearing results. PMID- 26160031 TI - Models for the effects of host movement in vector-borne disease systems. AB - Host and/or vector movement patterns have been shown to have significant effects in both empirical studies and mathematical models of vector-borne diseases. The processes of economic development and globalization seem likely to make host movement even more important in the future. This article is a brief survey of some of the approaches that have been used to study the effects of host movement in analytic mathematical models for vector-borne diseases. It describes the formulation and interpretation of various types of spatial models and describes a few of the conclusions that can be drawn from them. It is not intended to be comprehensive but rather to provide sufficient background material and references to the literature to serve as an entry point into this area of research for interested readers. PMID- 26160032 TI - EXPLAINING THE GAP IN ANTENATAL CARE SERVICE UTILIZATION BETWEEN YOUNGER AND OLDER MOTHERS IN GHANA. AB - Over two-thirds of pregnant women (69%) have at least one antenatal care (ANC) coverage contact in sub-Saharan Africa. However, to achieve the full life-saving potential that ANC promises for women and babies, a nuanced understanding of age specific gaps in utilization of ANC services is required. Using the 2008 Ghana Demographic and Health Survey of 1456 individuals, this study examined the disparities in the use of ANC services between younger and older mothers by applying four counterfactual decomposition techniques. The results show that cross-group differences in the explanatory variables largely account for the differentials in ANC service utilization between younger and older mothers. Birth order (parity) accounts for the largest share of the contribution to the overall explained gap in ANC utilization between the younger and older mothers, suggesting that ANC differentials between the two groups are probably due to biosocial factors. To a lesser extent, wealth status of the two groups also contributes to the overall explained gap in ANC service utilization. The policy implications of these findings are that in order to bridge the ANC service utilization gap between the two groups, policymakers must systematically address gaps in cross-group differences in the explanatory variables in order to increase the utilization of ANC to attain the minimum recommendation of four visits as per World Health Organization guidelines. PMID- 26160033 TI - The Stockholm experience: interhospital transports on extracorporeal membrane oxygenation. AB - INTRODUCTION: In severe respiratory and/or circulatory failure, extracorporeal membrane oxygenation (ECMO) may be a lifesaving procedure. Specialized departments provide ECMO, and these patients often have to be transferred for treatment. Conventional transportation is hazardous, and deaths have been described. Only a few centers have performed more than 100 ECMO transports. To date, our mobile ECMO teams have performed more than 700 transports with patients on ECMO since 1996. We describe 4 consecutive years (2010-2013) of 322 national and international ECMO transports and report adverse events. METHODS: Data were retrieved from our local databases. Neonatal, pediatric and adult patients were transported, predominantly with refractory severe respiratory failure. RESULTS: The patients were cannulated in 282 of the transports, and ECMO was started in these patients at the referring hospital and then they were transported to our ECMO intensive care unit. In 40 cases, the patient was already on ECMO. Of the transports, 60% were by aircraft, and the distances varied from 6.9 to 13,447 km. In about 27.3% of the transports, adverse events occurred. Of these, the most common were either patient-related (22%) or equipment-related (5.3%). No deaths occurred during transport, and transferred patients exhibited the same mortality rate as in-hospital patients. CONCLUSIONS: Long- and short-distance interhospital transports on ECMO can be safely performed. A myriad of complications can occur, but the mortality risk is very low. The staff involved should be highly competent in intensive care, ECMO physiology and physics, cannulation, intensive care transport and air transport medicine. They should also be skilled in recognition of risk factors involved in these patients. PMID- 26160034 TI - Free and Easy Wanderer Plus (FEWP) improves behavioral deficits in an animal model of post-traumatic stress disorder by stimulating allopregnanolone biosynthesis. AB - Post-traumatic stress disorder (PTSD) is a severe psychiatric condition defined as a "trauma and stress-related disorder". Dampened allopregnanolone biosynthesis has been implicated as a possible contributor to PTSD aetiology. Free and Easy Wanderer Plus (FEWP) is a traditional Chinese medicine previously shown to be effective in PTSD treatment. However, little is known about the role of allopregnanolone in the anti-PTSD effects of FEWP. To evaluate this, the single prolonged stress (SPS) model was used in the present study. SPS-induced rats were administered FEWP (at doses of 2.5, 5.0 and 10.0 mg/kg, p.o.) after induction of SPS from days 2 through 15. After exposure to SPS, behavioral assessments were determined, including the open-field test, the contextual fear paradigm, and the elevated plus-maze test. The experimental model rats were decapitated at the end of the behavioral tests and the level of allopregnanolone in the prefrontal cortex, hippocampus and amygdala was measured by enzyme linked immunosorbent assay (ELISA). The behavioral deficits of the SPS-induced rats were significantly reversed by FEWP (at doses of 5.0 and 10.0 mg/kg, p.o.). The level of allopregnanolone was increased by administration of FEWP. In summary, this study indicated that the anti-PTSD effects of FEWP were associated with allopregnanolone biosynthesis. PMID- 26160036 TI - MiR-495 is a Predictive Biomarker that Downregulates GFI1 Expression in Medulloblastoma. AB - BACKGROUND: Alterations in the expression level of miR-495 were recently observed in various tumours. Medulloblastoma is the most common malignant brain tumour in children. However, the clinical significance of miR-495 in medulloblastomas remains unclear. METHODS: The expression levels of miR-495 was examined in 62 archival formalin-fixed paraffin-embedded (FFPE) medulloblastoma specimens using TaqMan Real-time Quantitative PCR arrays. Immunohistochemistry was used to determine the expression of Gfi1 in medulloblastoma tissues, and a luciferase reporter assay was carried out to confirm whether Gfi1 is a direct target of miR 495. RESULTS: MiR-495 expression is repressed in medulloblastoma samples compared with normal cerebellum tissues. Furthermore, patients with a low level of miR- 495 showed significantly poorer survival, as determined by the log-rank test (P = 0.033). The multivariate analysis results showed that the miR-495 expression levels were an independent predictor of overall survival in medulloblastoma patients (P = 0.027; hazard ratio = 0.267). Our study provides the first demonstration that miR-495 directly interacts with the Gfi1 3'UTR to regulate Gfi1 at a post-transcriptional level and that the expression level of miR-495 is inversely correlated with the Gfi1 protein level in medulloblastoma specimens. CONCLUSION: Our results suggest that miR-495 may be a prognostic predictor in medulloblastoma and that Gfi1 is a potential functional target of miR-495. PMID- 26160035 TI - Leydig cell tumor in a patient with 49,XXXXY karyotype: a review of literature. AB - 49,XXXXY pentasomy or Fraccaro's syndrome is the most severe variant of Klinefelter's syndrome (KS) affecting about 1/85000 male births. The classical presentation is the triad: mental retardation, hypergonadotropic hypogonadism and radio ulnar synostosis. Indeed, the reproductive function of Fraccaro's syndrome is distinguished from KS. Besides, Leydig cell tumors are described in cases of KS, but never documented in the Klinefelter variants.We describe a young adult of 22 years old who presented with hyper gonadotropic hypogonadism, delayed puberty and bilateral micro-cryptorchidism. Chromosomal pentasomy was confirmed since infancy. Bilateral orchidectomy revealed a unilateral well-circumscribed Leydig cell tumor associated with bilateral Leydig cell hyperplasia.Inspired from reporting the first case of Leydig cell tumor in a 49,XXXXY patient, we summarize the particularities of testicular function in 49,XXXXY from one side, and the risk and mechanisms of Leydig cell tumorigenesis in Klinefelter variants on the other side. The histological destructions in 49,XXXXY testes and hypogonadism are more profound than in Klinefelter patients, with early Sertoli, Leydig and germ cell destruction. Furthermore, the risk of Leydigioma development in KS and its variants remains a dilemma. We believe that the risk of Leydigioma is much higher in KS than the general population. By contrast, the risk could be lower in the Klinefelter variants with more than 3 supplementary X chromosomes, owing to an earlier and more profound destruction of Leydig cells rendering them irresponsive to chronic Luteinizing hormone (LH) stimulation. PMID- 26160037 TI - Parental receptivity to child biomarker testing for tobacco smoke exposure: A qualitative study. AB - OBJECTIVE: Widespread tobacco smoke exposure (TSE) of children suggests that parents may be unaware of their children's exposure. Biomarkers demonstrate exposure and may motivate behavior change, but their acceptability is not well understood. METHODS: Sixty-five in-depth interviews were conducted with parents of young children, in smoking families in central Israel. Data were analyzed using thematic analysis. RESULTS: Consent to testing was associated with desire for information, for reassurance or to motivate change, and with concerns for long-term health, taking responsibility for one's child, and trust in research. Opposition to testing was associated with preference to avoid knowledge, reluctance to cause short-term discomfort, perceived powerlessness, and mistrust of research. Most parents expressed willingness to allow measurement by urine (83%), hair (88%), or saliva (93%), but not blood samples (43%); and believed that test results could motivate behavior change. CONCLUSIONS: Parents were receptive to non-invasive child biomarker testing. Biomarker information could help persuade parents who smoke that their children need protection. PRACTICE IMPLICATIONS: Biomarker testing of children in smoking families is an acceptable and promising tool for education, counseling, and motivation of parents to protect their children from TSE. Additionally, biomarker testing allows objective assessment of population-level child TSE. PMID- 26160038 TI - Using music[al] knowledge to represent expressions of emotions. AB - OBJECTIVE: Being able to identify expressions of emotion is crucial to effective clinical communication research. However, traditional linguistic coding systems often cannot represent emotions that are expressed nonlexically or phonologically (i.e., not through words themselves but through vocal pitch, speed/rhythm/tempo, and volume). METHODS: Using audio recording of a palliative care consultation in the natural hospital setting, two experienced music scholars employed Western musical notation, as well as the graphic realization of a digital audio program (Piano roll visualization), to visually represent the sonic features of conversation where a patient has an emotional "choke" moment. RESULTS: Western musical notation showed the ways that changes in pitch and rate correspond to the patient's emotion: rising sharply in intensity before slowly fading away. Piano roll visualization is a helpful supplement. CONCLUSIONS: Using musical notation to illustrate palliative care conversations in the hospital setting can render visible for analysis several aspects of emotional expression that researchers otherwise experience as intuitive or subjective. Various forms and formats of musical notation techniques and sonic visualization technologies should be considered as fruitful and complementary alternatives to traditional coding tools in clinical communications research. PRACTICE IMPLICATIONS: Musical notation offers opportunity for both researchers and learners to "see" how communication evolves in clinical encounters, particularly where the lexical and phonological features of interpersonal communication are concordant and discordant with one another. PMID- 26160039 TI - Correlates of type and quantity of child communication during pediatric subspecialty encounters. AB - OBJECTIVES: Understanding the factors associated with child communication during subspecialty encounters may inform interventions promoting shared decision-making in chronic disease management. Objectives were to (1) describe the quantity and quality of child communication during outpatient subspecialty encounters and (2) determine if and how the quantity and quality of child communication vary by demographic and visit characteristics. METHODS: We videotaped subspecialty clinic encounters involving 20 health care providers and 155 children with one of the following conditions: acute lymphoblastic leukemia (consolidation/maintenance), persistent asthma, cystic fibrosis, type 1 diabetes, and obesity. The Roter interaction analysis system was used to code child utterances into one of 10 discrete categories. RESULTS: Children exhibited a mean of 15% of all utterances made during clinical encounters. Children spoke more during obesity encounters. CONCLUSIONS: Similar to the findings of studies in primary care settings, children spoke infrequently during the subspecialty visits, and the most common utterances tended to be replies to questions from adults. PRACTICE IMPLICATIONS: In this study, there was relatively higher engagement of children during obesity clinic encounters in the area of lifestyle choices. Strategies used to engage children in conversation in obesity clinics may be useful for engaging children in other subspecialty clinics. PMID- 26160040 TI - Prevalence of lower extremity peripheral arterial disease in individuals with chronic immune mediated inflammatory disorders. AB - OBJECTIVE: To compare the prevalence of lower extremity peripheral artery disease (PAD) and to assess whether age-associated progression in ankle-brachial index (ABI) differs between individuals with chronic immune-mediated inflammatory diseases (CIID) and the general population. METHODS: Pooled analysis with data from individuals aged 50 years and older with ABI measurements, obtained from population-based cross-sectional studies conducted in Catalonia (Spain). Information on three CIID diagnoses (i.e., inflammatory bowel disease, systemic connective tissue disorders, and inflammatory polyarthropathies and spondylopathies, considered as one entity for purposes of analysis) was obtained from electronic medical records. To ascertain the statistical association between PAD and CIID, logistic regression models were fitted and adjusted for age, sex, and cardiovascular risk factors. We tested the interaction between age and CIID diagnosis for ABI values. RESULTS: We included 8799 individuals, 312 (3.6%) with CIID. The age-standardized prevalence of PAD was higher in the CIID group (12% vs. 6% in general population, p = 0.001), and the model adjusted for age, sex, and cardiovascular risk factors also showed higher risk in individuals with CIID [Odds Ratio (95% confidence interval) = 1.65 (1.15-2.38); p = 0.007]. The inflammatory polyarthropathies/spondylopathies diagnosis was significantly associated with PAD in the fully adjusted model [1.80 (1.18-2.75); p = 0.006]. The atherosclerotic process was accelerated in individuals with CIID, compared to the general population (p for interaction<0.001). CONCLUSION: In individuals with CIID, age-standardized prevalence of PAD was significantly higher than in the general population and the atherosclerotic process was accelerated. However, only inflammatory polyarthropathies/spondylopathies was associated with significant risk of PAD. PMID- 26160041 TI - Evaluation of polygenic cause in Korean patients with familial hypercholesterolemia - A study supported by Korean Society of Lipidology and Atherosclerosis. AB - BACKGROUND/OBJECTIVE: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in LDLR, APOB, or PCSK9. Polygenicity is a plausible cause in mutation-negative FH patients based on LDL cholesterol (LDL-C) associated single nucleotide polymorphisms (SNPs) identified by the Global Lipids Genetics Consortium (GLGC). However, there are limited data regarding the polygenic cause of FH in Asians. METHODS: We gathered data from 66 mutation negative and 31 mutation-positive Korean FH patients, as well as from 2274 controls who participated in the Korean Health Examinee (HEXA) shared control study. We genotyped the patients for six GLGC SNPs and four East Asian LDL-C associated SNPs and compared SNP scores among patient groups and controls. RESULTS: Weighted mean 6- and 4-SNP scores (0.67 [SD = 0.07] and 0.46 [0.11], respectively) were both significantly associated with LDL-C levels in controls (p = 2.1 * 10(-4), R(2) = 0.01 and p = 5.0 * 10(-12), R(2) = 0.02, respectively). Mutation-negative FH patients had higher 6-SNP (0.72 [0.07]) and 4-SNP (0.49 [0.08]) scores than controls (p = 1.8 * 10(-8) and p = 3.6 * 10(-3), respectively). We also observed higher scores in mutation-positive FH patients compared with controls, but the difference did not reach statistical significance. CONCLUSION: The present study demonstrates the utility of SNP score analysis for identifying polygenic FH in Korean patients by showing that small effect common SNPs may cumulatively elevate LDL-C levels. PMID- 26160042 TI - [Breast hematoma masking a sarcoma]. AB - Sarcomas account for less than 1% of malignant breast tumors. We present the case of a sarcoma (malignant fibrous histiocytoma) of the breast that debuted as a lump. The patient associated the lump with trauma, and the clinical, sonographic, and cytological findings were suggestive of a hematoma. The lump grew rapidly, and the follow-up sonogram one month later clearly revealed hypervascular solid poles. This atypical presentation is useful for reviewing the management of lesions suggestive of hematomas, which are often associated with nonspecific findings and occasionally with signs that raise suspicion of malignancy. The emergence of what appears to be a hematoma in the breast, even when accompanied by a history of trauma or a tendency toward bleeding, calls for prudence: very short-term follow-up and biopsy, even excisional biopsy, are recommended if the lesion does not evolve like a hematoma. PMID- 26160043 TI - Have CT and MR Angiography Replaced Catheter Angiography in Diagnosing Peripheral Arterial Disease? AB - PURPOSE: To determine whether MR angiography (MRA) and CT angiography (CTA) have replaced diagnostic catheter angiography (DCA) in diagnosing peripheral arterial disease. METHODS: Medicare Part B databases for 2002-2013 were reviewed. Current Procedural Terminology codes for extremity MRA, CTA, and DCA were selected. Physician specialty codes were used to classify providers as radiologists, cardiologists, or surgeons. Utilization rates per 100,000 Medicare beneficiaries were calculated. RESULTS: Among all specialties, the combined utilization rate of all 3 types of angiography increased from 917 per 100,000 in 2002 to 1,261 in 2006 (+38%), after which it remained stable until 2010, and then declined to 1,010 in 2013. The overall rate of MRA and CTA together increased from 89 in 2002 to 440 in 2006 (+394%), after which it leveled off, and then gradually decreased to 331 in 2013. In 2013, 33% of the total procedures were MRA or CTA, up from 10% in 2002. Radiologists performed >85% of MRA and CTA examinations. Among radiologists, the DCA utilization rate decreased by 75% from 2002 to 2013, whereas among cardiologists and surgeons together, the overall DCA utilization rate increased by 64% from 2002 to 2010 before dropping somewhat in 2011. CONCLUSIONS: Among radiologists, MRA and CTA have replaced DCA in diagnosing peripheral arterial disease. Although overall utilization of DCA has remained steady, it has risen sharply among cardiologists and surgeons, while dropping sharply among radiologists. Given the increased utilization of DCA among cardiologists and surgeons despite noninvasive alternatives, self-referral continues to be of concern in the setting of increasing health care costs. PMID- 26160045 TI - Non-cancer mortality in workers in the meat and delicatessen departments of supermarkets (1950-2006). AB - We studied non-cancer mortality in 10,701 workers in the meat and delicatessen departments of supermarkets because they have increased exposure to a variety of microorganisms that infect and cause disease in food animals such as cattle, pigs, sheep, and poultry, to which subjects in the general population are also exposed, albeit to a lesser degree. These workers were also exposed to fumes from the wrapping machine. Standardized mortality ratios were estimated in the cohort as a whole and in race/sex subgroups, using the US population for comparison. Study subjects were followed up from January 1950 to December 2006. Significantly increased deaths from diabetes, ischemic heart disease, pulmonary embolism, chronic bronchitis, peritonitis, intracranial and intraspinal abscess, other bacterial diseases, and significantly decreased deaths from diffuse diseases of connective tissue, functional diseases of the heart, intracerebral hemorrhage, occlusion/stenosis of the precerebral and cerebral arteries, and various types of accidents were observed in certain race/sex subgroups or in the cohort as a whole. The observed increased risks of several infectious conditions suggest that the increased occupational exposure to microorganisms may be responsible for at least some of the observed excess deaths, while exposure to fumes may also contribute to the excess of chronic bronchitis. The findings are important not only for supermarket workers and other workers in the meat and poultry industries, but also because the general population is exposed to these microorganisms found in food animals and their products. Nested case-control studies within cohorts that include both workers in supermarkets and other sectors of the meat and poultry industries, are now needed to examine specific risks from occupational exposures while adequately controlling for confounding factors, so that the role of these infectious agents in the occurrence of these diseases in workers and in general population subjects can be adequately assessed. PMID- 26160046 TI - Prioritization of in silico models and molecular descriptors for the assessment of ready biodegradability. AB - Ready biodegradability is a key property for evaluating the long-term effects of chemicals on the environment and human health. As such, it is used as a screening test for the assessment of persistent, bioaccumulative and toxic substances. Regulators encourage the use of non-testing methods, such as in silico models, to save money and time. A dataset of 757 chemicals was collected to assess the performance of four freely available in silico models that predict ready biodegradability. They were applied to develop a new consensus method that prioritizes the use of each individual model according to its performance on chemical subsets driven by the presence or absence of different molecular descriptors. This consensus method was capable of almost eliminating unpredictable chemicals, while the performance of combined models was substantially improved with respect to that of the individual models. PMID- 26160044 TI - Arabidopsis plants deficient in constitutive class profilins reveal independent and quantitative genetic effects. AB - BACKGROUND: The actin cytoskeleton is involved in an array of integral structural and developmental processes throughout the cell. One of actin's best-studied binding partners is the small ubiquitously expressed protein, profilin. Arabidopsis thaliana is known to encode a family of five profilin sequence variants: three vegetative (also constitutive) profilins that are predominantly expressed in all vegetative tissues and ovules, and two reproductive profilins that are specifically expressed in pollen. This paper analyzes the roles of the three vegetative profilin members, PRF1, PRF2, and PRF3, in plant cell and organ development. RESULTS: Using a collection of knockout or severe knockdown T-DNA single mutants, we found that defects in each of the three variants gave rise to specific developmental deficiencies. Plants lacking PRF1 or PRF2 had defects in rosette leaf morphology and inflorescence stature, while those lacking PRF3 led to plants with slightly elongated petioles. To further examine these effects, double mutants and double and triple gene-silenced RNAi epialleles were created. These plants displayed significantly compounded developmental defects, as well as distinct lateral root growth morphological phenotypes. CONCLUSION: These results suggest that having at least one vegetative profilin gene is essential to viability. Evidence is presented that combinations of independent function, quantitative genetic effects, and functional redundancy have preserved the three vegetative profilin genes in the Arabidopsis lineage. PMID- 26160047 TI - Neural correlates of deductive reasoning: An ERP study with the Wason Selection Task. AB - The Wason Selection Task (WST) is a well-known test of reasoning in which one turns over cards to test a rule about the two faces. Modifications were made to the WST to enable more direct and analytical investigation of reasoning processes. The modifications included extensive training to reduce variations in task interpretation, isolation of working memory in the decision phase, a separate rule for each card and variations in the form of the rule (number-letter as well as letter-number), separate scoring for each card, and inclusion of control cards that could be recognized by features without relational processing. The cognitive complexity of each card was also analyzed to enable investigation of this factor. Behavioral and event-related potential data were recorded. Negative cards differed from positive cards and control cards were differentiated from cards involved in inferences. The N2 component differentiated the negative conditions (not-P, not-Q cards) from the positive conditions (P, Q cards). The P3 component was largest for control and P cards (the simpler conditions). The late slow wave tended to show more sustained processing of not-P, not-Q and Q cards and was little influenced by the simpler control and P cards. Effects were interpreted in terms of cognitive complexity. In particular, the negative conditions had a larger N2 response than the positive conditions, reflecting greater cognitive complexity of the former and their sustained processing. PMID- 26160048 TI - A dual-potential electrochemiluminescence ratiometric approach based on graphene quantum dots and luminol for highly sensitive detection of protein kinase activity. AB - A novel Au NP mediated dual-potential ECL ratiometric approach for highly sensitive protein kinase activity and inhibition assay has been developed based on the simultaneous decrease of cathodic ECL from GQDs and enhancement of anodic ECL from luminol in the same bioanalysis. PMID- 26160049 TI - Relationship among C1q-fixing de novo donor specific antibodies, C4d deposition and renal outcome in transplant glomerulopathy. AB - BACKGROUND: The C1q-binding properties of donor specific antibodies (DSA) may be related to antibody-mediated rejection and poor outcome. METHODS: We retrospectively studied 35 kidney transplant recipients with transplant glomerulopathy (TG) and de novo DSA (dnDSA). C1q dnDSA were measured in the serum stored at renal biopsy and the association among C1q-fixing dnDSA, C4d deposition and graft loss was examined. RESULTS: Of the 35 patients with dnDSA and TG, 15 (42.9%) had C1q-positive dnDSA and 20 (57.1%) had C1q-negative dnDSA. Ten out of 15 patients with C1q-positive dnDSA (66.6%) and 5 with C1q-negative dnDSA (25%) had C4d positive staining renal biopsies (P=0.02), being the C1q-negative dnDSA/C4d-negative TG 42.9% of the total. The C1q-positive dnDSA group has significantly higher IgG DSA Class II MFI than the C1q-negative dnDSA group (P=0.004). Patients with C4d deposits have significantly higher IgG DSA MFI for both Class I and Class II than those without C4d deposits (P=0.02). We found a trend toward higher graft loss in the C1q-positive dnDSA group (60%) versus the C1q-negative dnDSA group (40%) without a statistical significance (P=0.31). CONCLUSION: Our study provides further characterization of TG associated with dnDSA. The major part of dnDSA-associated TG was C1q-negative and the presence of C1q-fixing dnDSA did not significantly correlate with graft outcome. PMID- 26160050 TI - Dietary methanol and autism. AB - The authors sought to establish whether maternal dietary methanol during pregnancy was a factor in the etiology of autism spectrum disorders. A seven item questionnaire was given to women who had given birth to at least one child after 1984. The subjects were solicited from a large primary care practice and several internet sites and separated into two groups - mothers who had given birth to a child with autism and those who had not. Average weekly methanol consumption was calculated based on questionnaire responses. 550 questionnaires were completed by women who gave birth to a non-autistic child. On average these women consumed 66.71mg. of methanol weekly. 161 questionnaires were completed by women who had given birth to an autistic child. The average estimated weekly methanol consumption for this group was 142.31mg. Based on the results of the Wilcoxon rank sum-test, we see a significant difference between the reported methanol consumption rates of the two groups. This study suggests that women who have given birth to an autistic child are likely to have had higher intake of dietary sources of methanol than women who have not. Further investigation of a possible link of dietary methanol to autism is clearly warranted. PMID- 26160051 TI - Propranolol during pregnancy for large chorioangioma. AB - Large chorioangiomas are frequently associated with adverse perinatal outcome. Its treatment remains invasive and controversial. Infantile hemangiomas which have numerous similarities with chorioangiomas are now usually treated with propranolol. This drug has been extensively used with a good tolerance during pregnancy in other indications. We report the first use of propranolol with the aim of limiting the increase in chorioangioma volume and avoiding the associated complications. The observed inhibition of the growth of the chorioangioma after introduction of propranolol argues for further evaluation of this treatment in this indication. PMID- 26160052 TI - Small-angle X-ray scattering method to characterize molecular interactions: Proof of concept. AB - Characterizing biomolecular interactions is crucial to the understanding of biological processes. Existing characterization methods have low spatial resolution, poor specificity, and some lack the capability for deep tissue imaging. We describe a novel technique that relies on small-angle X-ray scattering signatures from high-contrast molecular probes that correlate with the presence of biomolecular interactions. We describe a proof-of-concept study that uses a model system consisting of mixtures of monomer solutions of gold nanoparticles (GNPs) as the non-interacting species and solutions of GNP dimers linked with an organic molecule (dimethyl suberimidate) as the interacting species. We report estimates of the interaction fraction obtained with the proposed small-angle X-ray scattering characterization method exhibiting strong correlation with the known relative concentration of interacting and non interacting species. PMID- 26160053 TI - Diagnostic efficacy of CA 15-3 and CEA in the early detection of metastatic breast cancer-A retrospective analysis of kinetics on 743 breast cancer patients. AB - OBJECTIVE: We investigated the diagnostic capacity of CEA and CA 15-3 kinetics for the early detection of metastatic disease in comparison to fixed cut off values. METHODS: In a retrospective analysis, a total of 743 patients with early breast cancer and available baseline values of CEA and CA 15-3 were included. A reproducible increase of 100% of single or combined markers was considered as a strong indicator of metastatic disease. RESULTS: 187 patients developed metastatic disease and 556 remained disease-free. On the basis of tumor marker kinetics, we reached a specificity of >98% for both biomarkers and a sensitivity of 40.6% for CEA alone, 55.6% for CA 15-3 alone and 66.3% for the combination of both markers. Using fixed cut-off values (CEA: 4ng/mL, CA 15-3: 30U/mL) we ended up with a specificity of 86.3% and a sensitivity of 70.6% for the combination of CEA and CA 15-3. Using higher cut-off values (CEA: 6ng/mL, CA 15-3: 60U/mL) we reached a specificity of 96.9% and a sensitivity of 49.7% for the combination. CONCLUSION: We conclude that the interpretation of these markers in follow-up using individual baseline values and kinetics leads to a significant superior profile of specificity and sensitivity. PMID- 26160054 TI - B-type Natriuretic Peptide circulating forms: Analytical and bioactivity issues. AB - B-type Natriuretic Peptide (BNP), A-type and C-type Natriuretic Peptides (ANP and CNP) comprise a family of peptides that retain a common ring structure and conserved amino acid sequences. All are present in the heart, but only BNP and ANP are regarded as primarily cardiac secretory products. BNP and ANP, acting through a guanylyl cyclase receptor, increase sodium and water excretion by the kidney, induce vasodilation, reduce blood pressure, counteract the bioactivity of the renin-angiotensin-aldosterone and sympathetic nervous systems and possess anti-hypertrophic and anti-fibrotic properties. BNP is synthesised in cardiomyocytes first as the precursor peptide preproBNP. Removal of the signal peptide from preproBNP produces proBNP which is cleaved to produce the biologically active carboxy-terminal BNP peptide and the inactive N-terminal fragment, NT-proBNP. BNP, NT-proBNP, proBNP and the C-terminal portion of the BNP signal peptide have been detected in human plasma as well as multiple sub-forms including truncated forms of BNP and NT-proBNP, as well as variable glycosylation of NT-proBNP and proBNP. The origin of these circulating forms, their potential bioactivity and their detection by current analytical methods are presented in this review. PMID- 26160055 TI - Clinical insights by the presence of bipolar disorder in pseudohypoparathyroidism type 1A. AB - Pseudohypoparathyroidism type 1A and its association with bipolar disorder (BD) have never been reported so far. We report a new case with both clinical entities and discuss the potential pathophysiological mechanisms of this association (protein kinase A hypoactivation, parathyroid hormone, hypocalcemia, protein kinase C activation, vitamin D deficiency). In this patient, the correction of the underlying calcium and vitamin D deficiencies leads to a better BD outcome and lower dosage of psychopharmacological agents. The conclusions might be generalized for a better understanding and management of these conditions. PMID- 26160056 TI - Cancer survival in the context of mental illness: a national cohort study. AB - OBJECTIVE: To explore the reasons for worse cancer survival in people with experience of mental illness, including differences by cancer type and psychiatric diagnosis. METHOD: New Zealand breast and colorectal cancer registrations (2006-2010) were linked to psychiatric hospitalization records for adults (18-64 years). Cancer-specific survival was compared for recent psychiatric service users and nonusers using Cox regression. The contributions of deprivation, comorbidity and stage at diagnosis were assessed for those with schizophrenia or bipolar affective disorder (Group A) and others using mental health services (Group B). RESULTS: Of 8762 and 4022 people with breast and colorectal cancer respectively, 440 (breast) and 190 (colorectal) had recent contact with psychiatric services. After adjusting for confounding, risk of death from breast cancer was increased for Group A [Hazard Ratio (HR) 2.55 (95% confidence interval 1.49-4.35)] and B [HR 1.62 (1.09-2.39)] and from colorectal cancer for Group A [HR 2.92 (1.75-4.87)]. Later stage at diagnosis contributed to survival differences for Group A, and comorbidity contributed for both groups. Fully adjusted HR estimates were breast: Group A 1.65 (0.96-2.84), B 1.41 (0.95 2.09); colorectal: Group A 1.89 (1.12-3.17), B 1.25 (0.89-1.75)]. CONCLUSIONS: The high burden of physical disease and delayed cancer diagnosis in those with psychotic disorders contributes to worse cancer survival in New Zealand psychiatric service users. PMID- 26160057 TI - Three-dimensional quantitative assessment of lesion response to MR-guided high intensity focused ultrasound treatment of uterine fibroids. AB - RATIONALE AND OBJECTIVES: To investigate the response after magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) treatment of uterine fibroids (UF) using a three-dimensional (3D) quantification of total and enhancing lesion volume (TLV and ELV, respectively) on contrast-enhanced MRI (ceMRI) scans. METHODS AND MATERIALS: In a total of 24 patients, ceMRI scans were obtained at baseline and 24 hours, and 6, 12, and 24 months after MRgHIFU treatment. The dominant lesion was assessed using a semiautomatic quantitative 3D segmentation technique. Agreement between software-assisted and manual measurements was then analyzed using a linear regression model. Patients were classified as responders (R) or nonresponders (NR) on the basis of their symptom report after 6 months. Statistical analysis included the paired t-test and Mann-Whitney test. RESULTS: Preprocedurally, the median TLV and ELV were 263.74 cm(3) (30.45-689.56 cm(3)) and 210.13 cm(3) (14.43-689.53 cm(3)), respectively. The 6-month follow-up demonstrated a reduction of TLV in 21 patients (87.5%) with a median TLV of 171.7 cm(3) (8.5-791.2 cm(3); P < .0001). TLV remained stable with significant differences compared to baseline (P < .001 and P = .047 after 12 and 24 months). A reduction of ELV was apparent in 16 patients (66.6%) with a median ELV of 158.91 cm(3) (8.55-779.61 cm(3)) after 6 months (P = .065). Three-dimensional quantification and manual measurements showed strong intermethod agreement for fibroid volumes (R(2) = .889 and .917) but greater discrepancy for enhancement calculations (R(2) = .659 and .419) at baseline and 6 months. No significant differences in TLV or ELV were observed between clinical R (n = 15) and NR (n = 3). CONCLUSIONS: The 3D assessment has proven feasible and accurate in the quantification of fibroid response to MRgHIFU. Contrary to ELV, changes in TLV may be representative of the clinical outcome. PMID- 26160058 TI - KIDS OUT! Protocol of a brief school-based intervention to promote physical activity and to reduce screen time in a sub-cohort of Finnish eighth graders. AB - BACKGROUND: Adolescents' physical activity (PA) is decreasing and sedentary behavior (SB) increasing alarmingly. Insufficient PA and excessive SB are both related to various health risks indicating that interventions to promote adolescents' PA and to reduce their SB are needed. Schools have a great potential to reach most adolescents, and in Finland health education (HE) as stand-alone subject provides an excellent platform for health promotion. This paper describes the protocol and evaluation (RE-AIM) of an intervention developed for three HE lessons to increase PA and reduce SB during leisure among 8(th) graders. METHODS/DESIGN: All city-owned secondary schools in Tampere (n = 14) were invited to the study and were randomized in pairs to intervention (n = 7) and comparison group (n = 7). A specific content on PA and SB based on Health Action Process Approach model was integrated into routinely scheduled three HE lessons with the help of educational material: SoftGIS-questionnaire followed by feedback views on adolescents' current PA and SB, FeetEnergy-homework leaflet for adolescents, FeetEnergy-video in YouTube, FeetEnergy-poster for classroom and FeetEnergy leaflet for parents. In the comparison group standard HE lessons were held. The primary indicators of Effectiveness are changes in PA and SB and in their psychosocial factors as well as in parental interference with PA and SB. The measurement points are baseline, 4 weeks after the intervention and 7 months from baseline, the last indicating also the measurement point for individual level Maintenance. The measures are accelerometers, 7-day activity diaries and questionnaires. The evaluation of Reach, Adoption and Implementation is based on the data collected during the intervention. Maintenance at organizational level is assessed two years after the intervention with a questionnaire to the HE teachers. The intervention was implemented in 2012 and the last measurements to assess organizational Maintenance were conducted in the end of 2014. A detailed description of the protocol and evaluation is provided to enable replication and better understanding of the findings, which will be reported in 2015. DISCUSSION: The findings will add our current knowledge about the feasibility and effectiveness of integrating simple structured elements into the HE lessons to increase PA and reduce SB in adolescents. TRIAL REGISTRATION: NCT01633918 (June 27th, 2012). PMID- 26160059 TI - Olfactory drug effects approached from human-derived data. AB - The complexity of the sense of smell makes adverse olfactory effects of drugs highly likely, which can impact a patient's quality of life. Here, we present a bioinformatics approach that identifies drugs with potential olfactory effects by connecting drug target expression patterns in human olfactory tissue with drug related information and the underlying molecular drug targets taken from publically available databases. We identified 71 drugs with listed olfactory effects and 147 different targets. Taking the target-based approach further, we found additional drugs with potential olfactory effects, including 152 different substances interacting with genes expressed in the human olfactory bulb. Our proposed bioinformatics approach provides plausible hypotheses about mechanistic drug effects for drug discovery and repurposing and, thus, would be appropriate for use during drug development. PMID- 26160060 TI - Top 100 bestselling drugs represent an arena struggling for new FDA approvals: drug age as an efficiency indicator. AB - We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent years. PMID- 26160062 TI - Effect of the Combination of Hemodialysis and Hemoperfusion on Clearing Advanced Glycation End Products: A Prospective, Randomized, Two-Stage Crossover Trial in Patients Under Maintenance Hemodialysis. AB - Advanced glycation end products (AGEs) are protein-bound uremic toxins and are elevated in patients with the end-stage of renal disease. The present study sought to develop an effective method to remove the circulating AGEs from patients using the combination of hemodialysis (HD) and hemoperfusion (HP). Thirty-six patients undergoing maintenance HD for 3 months were randomly divided into two groups. Patients in Group 1 received HD, followed by the combined HP + HD treatment once, whereas patients in Group 2 were first treated with HP + HD and then they received the HD treatment alone. Patients treated with HD alone did not alter higher levels of serum AGEs. In contrast, patients treated with the combined HP + HD exhibited significantly lower levels of serum AGEs and TNF alpha. Results from this study demonstrate that the combination of HD + HP treatment may be an effective and better approach to remove the protein-bound uremic toxins and inflammatory cytokines. PMID- 26160061 TI - Prospective Technology Assessment of Synthetic Biology: Fundamental and Propaedeutic Reflections in Order to Enable an Early Assessment. AB - Synthetic biology is regarded as one of the key technosciences of the future. The goal of this paper is to present some fundamental considerations to enable procedures of a technology assessment (TA) of synthetic biology. To accomplish such an early "upstream" assessment of a not yet fully developed technology, a special type of TA will be considered: Prospective TA (ProTA). At the center of ProTA are the analysis and the framing of "synthetic biology," including a characterization and assessment of the technological core. The thesis is that if there is any differentia specifica giving substance to the umbrella term "synthetic biology," it is the idea of harnessing self-organization for engineering purposes. To underline that we are likely experiencing an epochal break in the ontology of technoscientific systems, this new type of technology is called "late-modern technology." -I start this paper by analyzing the three most common visions of synthetic biology. Then I argue that one particular vision deserves more attention because it underlies the others: the vision of self organization. I discuss the inherent limits of this new type of late-modern technology in the attempt to control and monitor possible risk issues. I refer to Hans Jonas' ethics and his early anticipation of the risks of a novel type of technology. I end by drawing conclusions for the approach of ProTA towards an early societal shaping of synthetic biology. PMID- 26160063 TI - Neighborhood-Level LGBT Hate Crimes and Bullying Among Sexual Minority Youths: A Geospatial Analysis. AB - The goal of this study was to evaluate a novel measure of environmental risk factors for bullying among sexual minority youths. Data on lesbian, gay, bisexual, and transgender (LGBT) assault hate crimes were obtained from police records, geocoded, and then linked to individual-level data on bullying and sexual orientation from the 2008 Boston Youth Survey Geospatial Dataset (N = 1,292; 108 sexual minorities). Results indicated that sexual minority youths who reported relational and electronic bullying were more likely to reside in neighborhoods with higher LGBT assault hate crime rates. There was no asso- ciation between LGBT assault hate crimes and bullying among heterosexual youths, pro- viding evidence for specificity to sexual minority youth. Moreover, no relationships were observed between sexual minority bullying and neighborhood level violent and property crimes, indicating that the results were specific to LGBT assault hate crimes. PMID- 26160064 TI - The difficulty of laparoscopic liver resection. AB - Grading of difficulty is needed for laparoscopic liver resection (LLR). Indications for LLR are expanding worldwide from minor to major resections, particularly in institutions having surgeons with advanced skills. If the degrees of surgical difficulty were defined, it would serve as a useful guide when introducing LLR and stepping up to the more advanced LLR. As no previous study has addressed the degrees of difficulty of various LLR procedures, we devised a practical scoring system for this purpose. We extracted the following five factors from preoperative information to score difficulty levels: (1) tumor location, (2) extent of liver resection, (3) tumor size, (4) proximity to major vessels, and (5) liver function. This difficulty index is comprised of the cumulative score for the five individual factors. There has not yet been a standard definition of difficulty. Our proposed scoring system might be a practical means of assessing the difficulty of LLR procedures. However, this system must be prospectively validated. PMID- 26160065 TI - Dynamic structural evolution of supported palladium-ceria core-shell catalysts revealed by in situ electron microscopy. AB - The exceptional activity for methane combustion of modular palladium-ceria core shell subunits on silicon-functionalized alumina that was recently reported has created renewed interest in the potential of core-shell structures as catalysts. Here we report on our use of advanced ex situ and in situ electron microscopy with atomic resolution to show that the modular palladium-ceria core-shell subunits undergo structural evolution over a wide temperature range. In situ observations performed in an atmospheric gas cell within this temperature range provide real-time evidence that the palladium and ceria nanoparticle constituents of the palladium-ceria core-shell participate in a dynamical process that leads to the formation of an unanticipated structure comprised of an intimate mixture of palladium, cerium, silicon and oxygen, with very high dispersion. This finding may open new perspectives about the origin of the activity of this catalyst. PMID- 26160066 TI - Saponin from the fruit of Solanum anguivi protects against oxidative damage mediated by Fe2+ and sodium nitroprusside in rat brain synaptosome P2 fraction. AB - Solanum anguivi fruit saponin has antidiabetic property via interference with cellular energy metabolism and inhibition of reactive oxygen species (ROS) generation. In the current study, brain specific in vitro anti-oxidant role of S. anguivi saponin was investigated in the P2 synaptosomal fraction of rat brain. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay, S. anguivi saponin concentration- dependently (10-200 ug/ml) reversed Fe2+ and sodium nitroprusside- induced decrease in mitochondrial activity via inhibition of ROS production, ROS-induced oxidation of protein and non-protein thiol-containing molecules and lipid peroxidation as measured by thiobarbituric acid reactive substances levels. Conclusively, S. anguivi fruit saponin represents a class of natural compounds with the ability to reverse synaptosomal disruption, loss of mitochondrial integrity and function often associated with the progression of Huntington's disease, Alzheimer disease, Parkinson disease and amyotrophic lateral sclerosis diseases. PMID- 26160067 TI - Assessment of pulmonary rehabilitation efficacy in chronic obstructive pulmonary disease patients using the chronic obstructive pulmonary disease assessment test. AB - AIM: We evaluated the relationship between chronic obstructive pulmonary disease (COPD) assessment test (CAT) and improvements after pulmonary rehabilitation (PR) and PR efficiency in COPD patients. METHODS & RESULTS: Forty COPD patients completed PR. After PR, mean change in CAT score was found to be 13 (p < 0.001), Medical Research Council (MRC), St George's Respiratory Questionnaire (SRGQ) and London Chest Activity Daily Living (LCADL) scores decreased, while Endurance Shuttle Walking Test (ESWT) time and Incremental Shuttle Walking Test (ISWT) distance increased significantly. Baseline CAT scores correlated with MRC, SRGQtotal, %FVC, ISWT, ESWT, LCADL. Change in CAT was significantly correlated with changes in MRC, SGRQtotal, LCADL-leisure scores, and ESWT. CONCLUSION: CAT score shows moderate degree correlation with some measures of outcome of PR and response to PR efficacy. PMID- 26160068 TI - Application of long-chain alcohols as faecal markers to estimate diet composition of horses and cattle fed with herbaceous and woody species. AB - Utilization of long-chain alcohols (LCOH) as diet composition markers in horses and cattle was assessed in a study conducted with 12 mature crossbreed mares (385+/-47 kg BW) and six adult non-lactating cows (499+/-36 kg BW) of Asturiana de los Valles breed. The LCOH data were combined with alkane and long-chain fatty acid (LCFA) data to test the applicability of combining these markers to estimate diet composition. Animals were randomly divided into groups of three animals and received a daily total amount of 1.0 kg dry matter/100 kg BW of diets composed of different proportions of ryegrass (Lolium perenne) and woody species (Ulex gallii and heather). Diet composition was estimated from even-chain LCOH (C(20)-OH to C(30)-OH) combined or not with alkane (C(25)-C(31) and C(33)) and/or LCFA (C(22) FA to C(28)-FA, C(30)-FA, C(32)-FA and C(34)-FA) concentrations in diet components and faeces by least-squares procedures, using marker faecal concentrations uncorrected for incomplete faecal recovery (FR0) or corrected using mean recoveries across diets within animal species (FR1). Results showed large differences between plant species in their LCOH profiles, and that these markers offered additional discriminatory information to that provided by alkanes and LCFA. The LCOH markers were incompletely recovered in the faeces of both animal species. In cattle, LCOH FR tended to increase with carbon-chain length in a linear manner in both diets (P < 0.001), whereas in horses overall data showed a curvilinear relationship between these variables. Combination of LCOH, LCFA and alkanes resulted in more accurate diet estimates. Correction of faecal LCOH concentrations to incomplete FR led to more accurate diet composition estimates in both animal species. Results obtained in this study suggest the usefulness of LCOH markers combined with alkanes and LCFA to estimate diet composition of horses and cattle grazing mixed grassy-woody plant communities. PMID- 26160069 TI - Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration. AB - Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L(del)). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L(del) flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L(del) flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency. PMID- 26160073 TI - Integrated care - a new buzz word in health care. PMID- 26160071 TI - miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation. AB - Basal autophagy is tightly regulated by transcriptional and epigenetic factors to maintain cellular homeostasis. Dysregulation of cardiac autophagy is associated with heart diseases, including cardiac hypertrophy, but the mechanism governing cardiac autophagy is rarely identified. To analyze the in vivo function of miR 199a in cardiac autophagy and cardiac hypertrophy, we generated cardiac-specific miR-199a transgenic mice and showed that overexpression of miR-199a was sufficient to inhibit cardiomyocyte autophagy and induce cardiac hypertrophy in vivo. miR-199a impaired cardiomyocyte autophagy in a cell-autonomous manner by targeting glycogen synthase kinase 3beta (GSK3beta)/mammalian target of rapamycin (mTOR) complex signaling. Overexpression of autophagy related gene 5 (Atg5) attenuated the hypertrophic effects of miR-199a overexpression on cardiomyocytes, and activation of autophagy using rapamycin was sufficient to restore cardiac autophagy and decrease cardiac hypertrophy in miR-199a transgenic mice. These results reveal a novel role of miR-199a as a key regulator of cardiac autophagy, suggesting that targeting miRNAs controlling autophagy as a potential therapeutic strategy for cardiac disease. PMID- 26160072 TI - Loading, release and stability of epirubicin-loaded drug-eluting beads. AB - PURPOSE: The aim of this study was to determine the loading efficiency, physico chemical stability and release of epirubicin-loaded DC BeadTM (Biocompatibles UK Ltd, a BTG International group company) (bead size 70-150 um (=DC BeadM1TM) and 100-300 um) after loading with epirubicin solution (2 mg/ml) or reconstituted powder formulation (25 mg/ml) and controlled storage. METHODS: DC BeadTM were loaded with 76 mg epirubicin solution (EpimedacTM, Medac GmbH) or 75 mg epirubicin powder formulation (FarmorubicinTM, Pharmacia Pfizer GmbH) per 2 ml of beads. Drug loading efficiency and stability were determined by measuring the epirubicin concentration in the excess solution after predetermined intervals (maximum 24 h) and different agitation conditions.Syringes with loaded beads were stored protected from light at room temperature. At predetermined intervals the beads were transferred into 200 ml phosphate buffered solution (pH 7.2) as elution medium and stirred automatically for 2 h not followed or followed by addition of 200 ml of 20% sodium chloride (=NaCl) solution and stirred for another 2 h to analyse the drug release and integrity of the epirubicin-loaded beads. Elution experiments were performed and samples taken periodically over a four-week period (day 0, 7, 14 and 28). A reversed-phase high-performance liquid chromatography assay with ultraviolet detection was utilized to analyse the concentration and purity of epirubicin. RESULTS: The loading procedure for DC BeadTM with epirubicin drug solutions resulted in a loading percentage of 95-99% within 6 h dependent on the bead size, epirubicin concentration in the loading solution and loading conditions. Loading levels remained stable and no epirubicin degradation products were observed over the period of 28 days, while the loaded beads were stored light protected at room temperature.Release of epirubicin into 200 ml phosphate buffered solution elution medium and additionally followed by release into the admixture with 200 ml 20% NaCl solution amounted to 5% and about 20% of the loaded epirubicin, respectively. Integrity of loaded epirubicin was proven over 28 days. CONCLUSIONS: Epirubicin can be loaded into DC BeadTM of different sizes using the epirubicin powder formulation (25 mg/ml) or epirubicin injection concentrate (2 mg/ml). Physico-chemical stability is maintained over a period of at least 28 days when stored light protected at room temperature. Elution of epirubicin is dependent on the volume and cation exchange capacity of the elution medium. PMID- 26160070 TI - Primary cilia and autophagic dysfunction in Huntington's disease. AB - Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by a single-gene mutation: a CAG expansion in the huntingtin (HTT) gene that results in production of a mutated protein, mutant HTT, with a polyglutamine tail (polyQ HTT). Although the molecular pathways of polyQ-HTT toxicity are not fully understood, because protein misfolding and aggregation are central features of HD, it has long been suspected that cellular housekeeping processes such as autophagy might be important to disease pathology. Indeed, multiple lines of research have identified abnormal autophagy in HD, characterized generally by increased autophagic induction and inefficient clearance of substrates. To date, the origin of autophagic dysfunction in HD remains unclear and the search for actors involved continues. To that end, recent studies have suggested a bidirectional relationship between autophagy and primary cilia, signaling organelles of most mammalian cells. Interestingly, primary cilia structure is defective in HD, suggesting a potential link between autophagic dysfunction, primary cilia and HD pathogenesis. In addition, because polyQ-HTT also accumulates in primary cilia, the possibility exists that primary cilia might play additional roles in HD: perhaps by disrupting signaling pathways or acting as a reservoir for secretion and propagation of toxic, misfolded polyQ-HTT fragments. Here, we review recent research suggesting potential links between autophagy, primary cilia and HD and speculate on possible pathogenic mechanisms and future directions for the field. PMID- 26160074 TI - The levels of trace elements and heavy metals in patients with acute migraine headache. AB - OBJECTIVE: To compare the levels of trace elements and heavy metal in patients with acute migraine and healthy controls. METHODS: The prospective study was conducted at Yuzuncu Yil University, Turkey, from May to July 2013, and comprised migraine patients and an equal number of healthy controls. International Headache Society classification was used for diagnosing migraine. Serum copper, zinc, lead, iron, cadmium, cobalt, manganese, and magnesium levels were measured in both groups. Metal concentrations were assessed by atomic absorption spectrophotometry. SPSS 13 was used for statistical analysis. RESULTS: There were 25 migraine patients with an average age of 36.4+/-8.9 years and 25 healthy controls with a mean age of 42.4+/-9.5 years. Cadmium, iron, manganese and lead levels were significantly elevated in the patients compared to the controls (p<0.05 each), while copper, magnesium and zinc were decreased and cobalt demonstrated no change. CONCLUSIONS: Trace elements and heavy metals may have a role in the genesis of considerable oxidative stress in patients with acute migraine headache. PMID- 26160075 TI - Difficult laparoscopic cholecystectomies. Is conversion a sensible option? AB - OBJECTIVE: To assess the overall impact of conversion of laparoscopic cholecystectomy to open cholecystectomy. METHODS: The observational descriptive study was conducted at Liaquat University Hospital, Jamshoro, Pakistan, and various private hospitals in the same town by the same surgeon from June 2011 to June 2013. All patients over 20 years of age and of either gender with symptomatic gallstone disease admitted and operated by laparoscopic technique were included. After initial work-up, laparoscopic cholecystectomy was performed by the conventional four-port technique. The variables studied included demographic details, duration of operation, operative complications, and incidence of conversion to open operation, post-operative complications and length of hospital stay. Data was analysed using SPSS 20. RESULTS: Of the 936 patients, 839(89.63%) were females and 97(10.36%) were males with an overall mean age of 39.88+/-8.66 (range: 29-65 years). Of the total, 108(11.53%) patients presented with a solitary gallstone; the remaining 828(88.46%) had multiple gall stones. Besides, 297(15.34%) had complicated gall stone disease. Tenderness in the right hypochondrium was observed in 897(95.83%) patients, while tenderness with palpable, tender gallbladder with fever and leucocytosis in 39(4.1%). Overall, 120(12.82%) patients presented with co-morbidities comprising diabetes mellitus in 43(4.59%), hypertension in 11(1.17%), ischaemic heart disease in 36(3.84%) and chronic obstructive pulmonary disease in 30(3.20%) patients. Further, 33(3.52%) patients were shifted from laparoscopic dissection to open cholecystectomy. CONCLUSIONS: A low threshold for conversion to open cholecystectomy can save the life of patients as continued dissection in difficult situation can lead to life-threatening complications. PMID- 26160076 TI - Genetic polymorphisms of hspa1b and hspa1l in infertile men. AB - OBJECTIVE: To investigate the relationship between the HSP 70 genepolymorphism and primary infertility in males with normal sperm-parameters. METHODS: The case control study was conducted in Sanliurfa, Turkey, from September 2010 to August 2011and comprised infertile males as cases and healthy fertile controls. Deoxyribonucleicacid was isolated from the blood of both groups, and polymorphisms of the HSPA1B gene (NM_005346.4, GI: 3304):c.1059G>A, (PstI G>A; dbSNP: rs1061581G>A) and HSPA1L gene (NM_005527.3, GI: 3305) c.1478C>T (NcoIC>T, dbSNP: rs2227956) were analysed with polymerase chain reaction-restriction fragment length polymorphism technique. SPSS version 11.5 was used for statistical analysis. RESULTS: Of the 140males in the study, 68(28.5%) were infertile cases and 72(51.4%) fertile controls. There was no statistically significant difference between GA (heterozygous) and AA (homozygous, polymorphic) genotypes of the c.1059G>A polymorphic point of the HSPA1B gene or between the A allele of the cases and controls (p>0.05). There was no statistically significant difference between the CT (heterozygote) and TT (homozygous, polymorphic) genotypes of the c.1478C>T polymorphic area of the HSPA1Lgene or between the T alleles of the cases and the controls (p>0.05). CONCLUSIONS: Infertility in males with normal sperm parameters was not significantly associated with HSPA1B:c.1059G>A and HSPA1L:c.1478C>T gene polymorphisms. Further prospective studies with larger sample sizes and different gene groups are required to clarify the issue. PMID- 26160077 TI - Morphological study of Pipelle biopsy specimens in cases of abnormal uterine bleeding. AB - OBJECTIVE: To determine the frequencies of common morphological patterns of abnormal uterine bleeding on Pipelle biopsy specimen. METHODS: The cross sectional study was conducted at PNS Shifa Hospital, Karachi, and comprised endometrial Pipelle biopsies of patients with abnormal uterine bleeding received between January 2013 and January 2014. Patient's age, marital status, parity and histopatholgical spectrum were recorded. SPSS 17 was used for data analysis. RESULTS: Of the 101 patients, 53(52.50%) presented with proliferative endometrium, 22(21.80%) had secretory endometrium, 13(12.9%) presented with chronic non-specific endometritis, 8(7.9%) had endometrial hyperplasia without atypia, and 5(5%) had endometrial hyperplasia with atypia. Besides, 86(85.1 %) were nulliparous; 15(14.9%) were parous; 92(91.1%) were married and 9(8.9%) were unmarried. CONCLUSIONS: The most common morphological pattern was proliferative endometrium. Though Pipelle has its own limitations, it performed better when endometrial pathology was global rather than focal. PMID- 26160078 TI - Retrospective comparison of Computed Tomography Enterography and Magnetic Resonance Enterography in diagnosing small intestine disease. AB - OBJECTIVE: To compare the efficacy of computed tomography enterography and magnetic resonance enterography in diagnosing small intestinal diseases. METHODS: The retrospective study comparing computed tomography enterography and magnetic resonance enterography for diagnosing diseases related to small intestine was conducted at Department of Radiology, Yantai Yuhuangding Hospital, Shandong, China, from July 2012 to February 2014. The efficacy of computed tomography enterography and magnetic resonance enterography results were evaluated for randomly-selected cases to compare the location and characteristics of small intestinal diseases together with small bowel endoscopy and clinical pathology observations. RESULTS: Of the 30 patients in the study, 19(63.3%) were males and 11 (36.7%) were females with an overall mean age of 33.6+/-19.2 years (range: 24 67 years). the clinical diagnostic accuracy of computed tomography enterography and magnetic resonance enterography was 24(80%) and 21(70%) cases respectively (p>0.05). CONCLUSIONS: Computed tomography enterography and magnetic resonance enterography are two techniques that complement each other for diagnostic purposes. PMID- 26160079 TI - Pattern of external injuries sustained during bomb blast attacks in Karachi, Pakistan from 2000 to 2007. AB - OBJECTIVE: To evaluate patterns of external injury resulting from bomb blasts in Karachi, and compare the injury profile resulting from explosions in open versus semi-confined blast environments. METHODS: The retrospective, cross-sectional study was conducted in Karachi and comprised relevant data from January 2000 to October 2007. Casualty medical records and medico-legal certificates of the victims presented to three large public-sector hospitals were evaluated using a self-designed proforma. SPSS 17 was used for statistical analysis. RESULTS: Of the 1146 victims, data of 481(42%) represented the final study sample. Of these, 306(63.6%) were injured in open spaces and 175(36.4%) in semi-confined spaces. Of the 896 recorded injuries, lacerations were encountered as external injury in 427(47.7%) cases, followed by penetrating wounds in 137(15.3%). Lower and upper extremities were injured in 348(38.8%) and 170(19%) victims respectively. Open and semi-confined blast environments produced specific injury pattern and profile (p<0.001). CONCLUSIONS: External injuries sustained during bomb blast attacks in Karachi demonstrated specific injury patterns and profiles. Further studies are required to account for internal injuries and classification of injuries based on standardised scoring systems. PMID- 26160080 TI - Feasibility, relevance and effectiveness of teaching and assessment of ethical status and communication skills as attributes of professionalism. AB - OBJECTIVE: To examine the feasibility and effectiveness of teaching and assessing professionalism in a developing country. METHODS: The pre-intervention and post intervention study was conducted from January to August 2012 and comprised 7 workshops of three days each that were held at four teaching hospitals of Khyber Pakhtunkhwa province in Pakistan. Overall, there were 10 Objective Structured Clinical Examination stations and 10 written scenarios. After the pre-test, workshop was held on various aspects of professionalism which was considered 'intervention', and it was followed by a post-test similar to the pre-test at the end of day 3. Stata 12 was used for all statistical analyses. RESULTS: There were 136 postgraduate residents in the study. The correlation between Objective Structured Clinical Examination stations and written exam for pre-test was 0.42 (p<0.001), while for post-test the correlation was 0.17(p=0.046). Correlation between pre-test written and post-test Objective Structured Clinical Examination stations was 0.23 (p=0.001), but the correlation between pre-test Objective Structured Clinical Examination stations and post-test written was not significant (p>0.05).The standardised effect size for the adjusted regression was 0.37 for both comparisons (p<0.001).Mean pre-test scores were 38.13+/-13.13% vs. 76.50+/-14.4%for the post-test score (p<0.001). CONCLUSIONS: Although post-test scores increased significantly both for the Objective Structured Clinical Examination stations and the written scenarios, the former has shown a higher reliability compared to the written test. Furthermore, teaching and assessment of professionalism was found relevant, effective and feasible in resource constrained countries. Teaching and assessment of professionalism has become globally relevant and is recommended to be included in the curricula of medical institutions. PMID- 26160081 TI - Open proximal & distal fractures of tibia treated with Naseer Awais External Fixator with T-clamp. AB - OBJECTIVE: To compare the outcome of the open proximal and distal fractures of tibia treated by Nasser Awais External Fixtator with T-clamp. METHODS: The descriptive case series was conducted from August 2009 to July 2012 at Department of Orthopaedic Surgery & Traumatology, Liaquat University of Medical & Health Sciences, Jamshoro, and comprised in-patients of open proximal and distal fractures of tibia who were divided into two equal groups: group A had distal and group B had proximal patients. All patients had extra-articular open fractures Gustilo I, II, IIIA and IIIB of proximal and distal end of tibia between 15 and 60 years of age who had arrived within 8 hours of the injury. Below-knee plaster cast was applied for 02 to 03 weeks after the removal of Nasser Awais External Fixtator and all patients were followed up for 12 months. SPSS 17 was used for statistical analysis. RESULTS: Overall, there were 30 patients; 15(50%) in each of the two groups. The mean age in group A was 28.9+/-9.43 years and 34.3+/-14.60 years in group B. There were 11(73.3%) males and 4(26.7%) females in group A, and 15(100%) males in-group B. Mean fracture union time in group A was 17.20+/-2.93 weeks (range: 11-23 weeks) and in group B it was 23.53+/-2.44 weeks (range: 19-28 weeks). Ankle joint stiffness occurred in 2(6.7%) cases that were in group A, and knee joint stiffness was seen in 2(6.7%) cases and they were in group B. CONCLUSIONS: Nasser Awais External Fixator with T-Clamp was a safe technique and promoted the union with a low complication rate with less union time in distal tibial fracture compared to proximal fracture. PMID- 26160082 TI - Pre-operative antibiotic use reduces surgical site infection. AB - OBJECTIVE: To assess the efficacy of World Health Organisation Surgical Safety Checklist as a simple, reliable and effective tool to ensure appropriate administration of intravenous antibiotics. METHODS: The prospective interventional study was conducted in three phases at Mayo Hospital, Lahore, from May 2011 to January 2012. The first phase comprised baseline data collection, followed by implementation of World Health Organisation Surgical Safety Checklist, and finally post-implementation data collection. The duration of each phase was 3 months. Primary end points were discharge from hospital, 30 days or death of the patient. RESULTS: Of the 613 patients in the study, 303(49.4%) were in the pre-implementation phase and 310(50.5%) in post-implementation phase. Adherence of optimal administration of antibiotic increased from 114(37.6%) to 282(91%) (p<0.001). The rate of post-operative infection fell from 99(32.7%) to 47(15.2%) (p<0.001). Mean hospital stay was reduced from 7.8+/-5.7 days to 6.5+/ 5.6 days (p<0.001). CONCLUSIONS: Appropriate and timely administration of antibiotic reduced surgical site infection by more than half. Hospital stay was shortened by 1.3 days on average which results in considerable reduction in morbidity, mortality and costs. PMID- 26160083 TI - Comparison of single intra operative versus an intra operative and two post operative injections of the triamcinolone after wedge excision of keloids of helix. AB - OBJECTIVE: To compare single intra-operative versus an intra-operative and two post-operative injections of triamcinolone after wedge excision of keloids of helix. METHODS: The randomised controlled trial was conducted at the King Edward Medical University, Lahore, from January, 2011, to March, 2014, and comprised female patients over 14 years of age presenting with post-piercing keloids of helix not treated previously by any means and amenable to wedge excision. The subjects were divided into Group A who were given a single intra-operative injection of triamcinolone, and Group B who had an intra-operative and two post operative injections of triamcinolone. Extra-lesional wedge excision of keloids was done, followed by infiltration of flaps and wound base with 0.5-1cc of triamcinolone 40mg/cc. Group B patients were given additional injections of triamcinolone at 1st and 2nd monthly visits. Both groups were observed for the evidence of hypertrophy or complications. Development of hypertrophy within one year of completion of treatment was considered recurrence. RESULTS: The 70 patients in the study were divided into two equal groups of 35(50%) each. The mean age of Group A was 22.34+/-4.95 years and that of Group B was 22.88+/-4.22 years (p=0.624). The Mean size of the keloids was 2.54+/-0.516 cm(2) in Group A and 2.61+/-0.569 cm(2) in Group B (p=0.613). Recurrence rate in Group A was 3(8.5%) and 2(5.7%) in Group B (p= 0.64). The complication rate was 3(8.5%) in Group A and 8(22.8%) in Group B (p=0.10). CONCLUSIONS: Single injection of triamcinolone was as effective as three in reducing recurrence with less complication rate. PMID- 26160084 TI - An application of a theory of planned behaviour to determine the association between behavioural intentions and safe road-crossing in college students: perspective from Isfahan, Iran. AB - OBJECTIVE: To identify the determinants of behavioural intention towards safe road-crossing among college students. METHODS: The cross-sectional study was conducted in 2013-14 and comprised students of Isfahan University of Medical Sciences, Isfahan, Iran. A self-administrated questionnaire was distributed among the subjects related to road-crossing based on the theory of planned behaviour. Data was analysed using SPSS 21. RESULTS: Of the 300 questionnaires distributed, 278(92.66%) were returned completed. The mean age of the subjects was 23.16+/ 3.66 years. There were 149(53.6%) females and 129(46.4%) males, with females crossing the street more safely than the males. There was a significant difference between the genders for subjective norms (p=0.001), perceived behavioural control (p=0.002) and behavioural intention (p=0.001), but no differences were traced with respect to attitude towards safe crossing (p=0.597). Results showed a direct and positive correlation between attitude towards safe crossing (r=0.276; p=0.001), subjective norms (r=0.368; p=0.001) and perceived behavioural control (r=0.419; p=0.000) with behavioural intention to safe crossing. CONCLUSIONS: The attitude towards safe crossing and perceived behavioural control had significant effect on behavioural intention among college students. PMID- 26160085 TI - Evaluation of Hormone Receptor Status (ER/PR/HER2-neu) in Breast Cancer in Pakistan. AB - OBJECTIVE: To evaluate the biological markers that are commonly assessed in breast cancer to estimate a patient's response to endocrine therapy and their prognosis for better clinical outcomes. METHODS: The retrospective study was conducted at Bahawalpur Institute of Nuclear Oncology and comprised record of early breast cancer patients who gave positive diagnostic tests for hormone receptors status i.e. immunohistochemical test and were treated during 2007-2013. Data of oestrogen, progesterone and human epidermal growth factor receptor 2 expression status was analysed. SPSS 12 was used for statistical analysis. RESULTS: Overall record of 345 patients was studied of whom 149(43%) were identified to have positive hormone receptor status.. The age of the patients ranged from 24 to 86 years with 97(65%) in 25-50 years, 46(30.8%) 51-75 years and 6(4.08%)in 76-100 years. Besides, 76(51%) patients had carcinoma of right breast; 86(58%) were diagnosed as Stage III, 55(37%) Stage II and 8(5.3%) Stage IV. Those diagnosed with oestrogen receptor (positive status) were 16(10.7%), human epidermal growth factor receptor 2 over-expression 13(8.7%), oestrogen/progesterone hormone receptor positivity (or luminal A) 76(51%) and 35(23.4%) patients were positive for all the three receptors. CONCLUSIONS: About half of the patients were diagnosed with a positive hormone status and it was observed that in most of the cases disease was metastasised to distant organs. PMID- 26160086 TI - Factors associated with stress among medical students. AB - OBJECTIVE: To determine the probable factors responsible for stress among undergraduate medical students. METHODS: The qualitative descriptive study was conducted at a public-sector medical college in Islamabad, Pakistan, from January to April 2014. Self-administered open-ended questionnaires were used to collect data from first year medical students in order to study the factors associated with the new environment. RESULTS: There were 115 students in the study with a mean age of 19+/-6.76 years. Overall, 35(30.4%) students had mild to moderate physical problems, 20(17.4%) had severe physical problems and 60(52.2%) did not have any physical problem. Average stress score was 19.6+/-6.76. Major elements responsible for stress identified were environmental factors, new college environment, student abuse, tough study routines and personal factors. CONCLUSIONS: Majority of undergraduate students experienced stress due to both academic and emotional factors. PMID- 26160087 TI - Development and validation of a semi-quantitative food frequency questionnaire to assess dietary intake in Turkish adults. AB - OBJECTIVE: To validate the original food frequency questionnaire in Turkish adult population. METHODS: The cross-sectional study was conducted in June and December 2008 and 2009, and comprised adults of either gender aged 30-70 years. All subjects were Caucasians and were native Turkish speakers. The food frequency questionnaire containing 229 most frequently consumed foods under 7 topics was used for data collection. It was completed twice and the 24-hour dietary recall four times in a year. In order to assess the validity of the questionnaire, Pearson correlation, attenuation coefficient, measures of agreement between the two methods, weighted kappa statistics and Bland-Altman plots were employed. SPSS 16 was used for statistical analysis. RESULTS: Of the 120 subjects in the study, 71(59%) were males and 49(41%) were females with an overall mean age of 50.16+/ 9.76 years. The correlation of estimated nutrient intake between the food frequency questionnaire and 24-hour dietary recall varied between 0.200 and 0.468, energy-adjusted regression was between 0.044 and 0.611 and attenuation coefficients of regression were between 0.339 and 0.658 for the selected macro and micro nutrients. Bland-Altman plots showed an acceptable agreement between the two methods. When nutrient intake was categorised in quartiles, proportions of the same or adjacent quartiles were 98.3%, 98.4%, 98.3%, 96.7% and 95% for energy, fat, protein, carbohydrates and fibre, respectively. CONCLUSIONS: The first food frequency questionnaire developed in Turkish language was an adequate and valid tool to assess the nutritional habits of the local population. PMID- 26160088 TI - Difficulties experienced by caregivers of patients diagnosed with osteogenesisimperfecta (OI): example of a hospital. AB - OBJECTIVE: To identify the difficulties experienced by medical caregivers of inpatients diagnosed with osteogenesisimperfecta. METHODS: The descriptive, cross sectional study was conducted at a university hospital in western Turkey from April to May, 2012, and comprised relatives providing care to patients who were diagnosed with osteogenesisimperfecta and were being treated in the paediatric endocrinology unit. Data was collected via face-to-face interviews with patient relatives. The 35-itemquestionnaire had 16 open-ended and 19 close-ended questions. RESULTS: The mean age of the 46 caregivers was 35.52+/-6.65 years, and 43(93.5%) of them were mothers. All of them said they felt anxious (100%), while 44(95.7%) felt sad/sorrow, 41(89.1%) puzzled, 40(87.0%) nervous, 40(87.0%) frightened, 39(84.8%) disappointed, 29(63%) shocked, and 28(60.9%) depressed when they first heard the diagnosis. Overall, 26(56.5%) experienced physical, 45(97.8%) psychological, 45(97.8%) social, and 35(76.1%) economic changes and difficulties, while 24(52.1%) had no social support. Of all the patient relatives, 38(82.6%) were unable to obtain adequate information about the disorder from the healthcare team. CONCLUSIONS: Caregivers of patients diagnosed with osteogenesisimperfecta experienced psychological and social difficulties.. PMID- 26160089 TI - Frequency, causes and outcome of neonates with respiratory distress admitted to Neonatal Intensive Care Unit, National Institute of Child Health, Karachi. AB - OBJECTIVE: To determine the frequency, aetiology and outcome of respiratory distress in neonates in intensive care unit. METHODS: The descriptive cross sectional study was conducted at the Neonatal Intensive Care Unit, National Institute of Child Health, Karachi, from October 2009 to March 2010. It comprised neonates aged day 0 to 28 who were admitted to Neonatal Intensive Care Unit. The neonates were screened first for respiratory distress and presence of one or more signs and symptoms. History, examination and investigations were carried out to find out various aetiologies of respiratory distress. Outcome was measured in terms of discharge and death. Data was analysed using SPSS12. RESULTS: Of the 205 neonates in the study, 120(58.6%) were boys and 85(41.4%) were girls The overall mean age was 70.58+/-110.02 hours and the mean gestational age was 36.32+/-2.72 weeks while the mean weight was 2.41+/-2.4kg. Respiratory rate >60/min was found in all (100%) the neonates. In terms of signs and symptoms, 125(60.9%) had grunting, 205(100%) had subcostal retractions and nasal flaring, and 81(40%) had cyanosis. The aetiologies observed were birth asphyxia, sepsis, transient tachypnoea of the newborn, pneumonia, meconium aspiration syndrome and respiratory distress syndrome in 22(10.75%), 37(18.05%), 29(14.1%), 36(17.6%), 34(16.7%) and 47(23.0%) neonates respectively. The incidence of neonates with respiratory distress was 68(33.3%). CONCLUSIONS: The frequency of respiratory distress among the neonates was high, while mortality was high in neonates with respiratory distress, especially in pre-term and low birthweight neonates. Early diagnosis and management is important for better outcome. PMID- 26160090 TI - Review and analysis of quality healthcare system enhancement in developing countries. AB - Quality has multidimensional perspectives. It is a continuous and dynamic process. A systematic search of national and international literature was conducted from peer-reviewed databases MEDLINE, CINAHL and PubMed during January to July 2012. There are many frameworks to assess and measure quality. All frameworks give some levels in which quality could be assessed. Therefore, multiple frameworks should be used for measuring quality based on the situation and environment. Measuring quality is very important for primary healthcare programme, especially for developing countries because if we will not do quality assessment, our resources will not be utilised effectively and people may divert to curative services. Thus, in developing countries where healthcare system needs to optimise resources for increased population coverage and scale up the care, quality approaches can suggest workable solutions to using resources appropriately. PMID- 26160091 TI - Correlations between stress hormone levels in umbilical cord blood and duration of delivery. AB - Correlations between umbilical cord blood concentration of stress response hormone cortisol and prolactin, and delivery duration were examined. Thirty-three cases were selected in which both mothers and neonates were healthy, and the neonates were delivered at full term. The umbilical cord blood was collected at the time of delivery and concentrations of cortisol and prolactin were measured. The cortisol level was significantly higher after vacuum-assisted delivery than after spontaneous delivery (p=0.044). Significant positive correlations (p=0.0289) were observed between cortisol level and delivery duration. In particular, the duration of the second stage of delivery showed stronger positive correlation (p=0.0304) with the cortisol level. The prolactin level showed weak correlation with the duration of full delivery and the second stage of delivery. The findings suggest that foetuses may respond to stress by uterine contraction during delivery. PMID- 26160092 TI - Metaplastic squamous cell carcinoma of breast. A pathology case report with review of literature. AB - Metaplastic Breast Carcinoma (MBC) is a group of rare breast cancers; squamous cell carcinoma (SCC) is its most common member. Due to rarity of the condition, frequent case reports have been published of late. In the last one year alone, there were about a dozen such reports. Here we report a case of primary squamous cell carcinomain a 62-year-old female, with a 3.5cm mass in the left breast. Biopsy and mastectomy reports confirmed Metaplastic carcinoma, with 21 benign lymph nodes.. The tumour was triple negative and cytokeratin 5/6 positive. We are reporting the first case of squamous cell carcinoma of breast from our region, and we recommended large multi centre studies. PMID- 26160093 TI - Retroperitoneal Haematom due to Spontaneous Rupture and Haemorrhage of Adrenal Cyst Presenting with Grey Turner's Sign. AB - Spontaneous retroperitoneal haemorrhage is a rare entity and a potentially life threatening condition. A 41-year-old woman presented to our emergency department with left flank pain and dysuria. Her physical examination disclosed left abdominal and costovertebral angle tenderness, left flank ecchymosis (Grey Turner sign). Abdominal computerised tomography revealed spontaneous retroperitoneal haemorrhage. She was discharged after 10 days with recommendation of urology follow-up. PMID- 26160094 TI - Two accidental hanging cases of children. AB - The cases emphasise the implementation of safety measurements which may prevent the occurrence of accidental hanging in children. Two accidental hanging cases were autopsied at The Council of Forensic Medicine, Bursa Group Chairmanship, Morgue Department. The inquest papers written by police were examined and the scenes and autopsy findings are presented. The first case was a four year old girl and the second case was a five year old boy. Their manners of death were determined as an accident. The first accident occurred out of home, but the second accidental hanging occurred at home. It was seen that childhood deaths due to hanging are preventable. Detailed medico-legal investigation in order to elucidate the manner of death is required in similar cases. PMID- 26160095 TI - Intermittent levetiracetam treatment in five patients with catamenial epilepsy. AB - Catamenial epilepsy is a periodic increase in seizure frequency in women with epilepsy during menstruation, or at any specific point in the menstrual cycle. We present five cases who attended the epilepsy outpatient clinic at the Sichuan Provincial People's Hospital, China, and who suffered catamenial epilepsy and received intermittent Levetiracetam (LEV) treatment 1 week prior to and post menstruation around each menstrual period. The patients responded positively and seizures were controlled with a dose of 0.5g, twice daily in 3(67%) patients, and by a dose of 0.75g twice daily in the remaining 2(33%) patients, indicating that intermittent LEV therapy could be an effective strategy for the treatment of catamenial epilepsy. PMID- 26160096 TI - Once-weekly glucagon-like peptide 1 receptor agonists. AB - The once-weekly glucagon-like peptide 1 receptor agonists (QW GLP1RA) represent a major advancement in diabetes pharmaco-therapeutics. This review describes the basic, clinical, and comparative pharmacology of this novel class of drugs. It highlights the clinical placement and posology of these drugs. PMID- 26160097 TI - Starting titrating and intensifying metformin. AB - Most persons with type 2 diabetes are treated with oral anti diabetic drugs (OADs). The drug of choice for initiating OAD therapy, in most cases, is metformin. This communication discusses how to start, titrate, and intensify metformin therapy in primary care. It discusses ways of improving tolerance to, and enhancing acceptability of, metformin in people with diabetes. PMID- 26160098 TI - Breast cancer prevention and role of the general physician. PMID- 26160099 TI - Prosthetic valve thrombosis in a patient with mitral valve replacement. AB - Prosthetic valve thrombosis within one year after mitral valve replacement is rarely seen in patients on warfarin therapy and without any risk factor. Here, we describe a case of a 39-year- old female, who presented with dyspnoea and shortness of breath 11 months after mitral valve replacement. The echocardiogram revealed severe valvular stenosis due to presence of clots on the mitral valve and restricted motion of the mitral leaflets. As a result of deterioration of general condition and haemodynamic un-stability, plan was made to re-operate for her valve replacement surgery. This case report highlights the diagnosis, prevention and management of patients with prosthetic valve thrombosis following mitral valve replacement. PMID- 26160100 TI - HNF1B-associated clinical phenotypes: the kidney and beyond. AB - Mutations in HNF1B, the gene encoding hepatocyte nuclear factor 1beta are the most commonly identified genetic cause of renal malformations. HNF1B was first identified as a disease gene for diabetes (MODY5) in 1997, and its involvement in renal disease was subsequently noted through clinical observations in pedigrees affected by MODY5. Since then, a whole spectrum of associated phenotypes have been reported, including genital malformations, autism, epilepsy, gout, hypomagnesaemia, primary hyperparathyroidism, liver and intestinal abnormalities and a rare form of kidney cancer. The most commonly identified mutation, in approximately 50 % of patients, is an entire gene deletion occurring in the context of a 17q12 chromosomal microdeletion that also includes several other genes. Some of the associated phenotypes, especially the neurologic ones, appear to occur only in the context of this microdeletion and thus may not be directly linked to HNF1B. Here we review the spectrum of associated phenotypes and discuss potential implications for clinical management. PMID- 26160103 TI - [Dacryolith in a lacrimal duct]. AB - A 31-year-old woman presented with a prominent, yellowish conjunctival mass in the left temporal canthus that had persisted for 3 months despite previous puncture. Repeat incision and curettage produced an 8 mm long concretion. A histopathological examination revealed a dacryolith in the lacrimal duct. This pathology is very rare in this location but has to be considered as a differential diagnosis when patients present with prominence and discomfort in the area of the temporal canthus. The treatment of choice is resection of the dacryolith and irrigation of the lacrimal ducts with penicillin. PMID- 26160102 TI - NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. AB - Many cellular RNAs require modification of specific residues for their biogenesis, structure, and function. 5-methylcytosine (m(5)C) is a common chemical modification in DNA and RNA but in contrast to the DNA modifying enzymes, only little is known about the methyltransferases that establish m(5)C modifications in RNA. The putative RNA methyltransferase NSUN6 belongs to the family of Nol1/Nop2/SUN domain (NSUN) proteins, but so far its cellular function has remained unknown. To reveal the target spectrum of human NSUN6, we applied UV crosslinking and analysis of cDNA (CRAC) as well as chemical crosslinking with 5 azacytidine. We found that human NSUN6 is associated with tRNAs and acts as a tRNA methyltransferase. Furthermore, we uncovered tRNA(Cys) and tRNA(Thr) as RNA substrates of NSUN6 and identified the cytosine C72 at the 3' end of the tRNA acceptor stem as the target nucleoside. Interestingly, target recognition in vitro depends on the presence of the 3'-CCA tail. Together with the finding that NSUN6 localizes to the cytoplasm and largely colocalizes with marker proteins for the Golgi apparatus and pericentriolar matrix, our data suggest that NSUN6 modifies tRNAs in a late step in their biogenesis. PMID- 26160104 TI - [Visual impairment due to rare optic nerve tumor]. AB - A 49-year-old male patient presented with acute symptoms of reduced vision and relative afferent pupillary defects. Static perimetry testing revealed severe visual field defects and the diagnosis of neuritis of the optic nerve was suspected. A magnetic resonance imaging (MRI) scan was performed and showed an intraocular right-sided semicircular mass around the optic nerve which was partially calcified in computer tomography (CT). The diagnosis of an optic nerve sheath meningioma was made. The visual acuity and visual field defects improved under therapy with prednisolone. Therapeutic options were discussed in an interdisciplinary board but no intervention is planned so far and only regular follow-up controls have been arranged. PMID- 26160105 TI - [Ocular prosthetics. Fitting, daily use and complications]. AB - BACKGROUND: Ocular prosthetics make a decisive contribution to the functional, esthetic and psychosomatic rehabilitation of patients after ocular extirpation. OBJECTIVES: This article provides an overview of the fitting, daily care and complications of ocular prosthetics. METHODS: The study comprised a PubMed literature review and own clinical results. RESULTS: Ocular prosthetics made from cryolite glass or perspex can be manufactured and fitted 5-8 weeks after removal of the eye. During this period a conformer is placed within the conjunctival sac in order to prevent scar formation and shrinking of the socket. Artificial eyes can be worn continuously, only interrupted by a short but regular cleaning procedure. Artificial tears and lid hygiene improve the comfort of wearing. Glass prostheses have to be renewed every 1-2 years, while perspex prostheses need to be polished once a year. Complications, such as giant papillary conjunctivitis or blepharoconjunctivitis sicca are facilitated by poor fit, increased age and inappropriate care of the prosthetic device. In the case of socket shrinkage or anophthalmic socket syndrome, surgical interventions are needed to re-enable the use of an artificial eye. CONCLUSION: Adequate fitting, daily care of ocular prosthetics and therapeutic management of associated complications are mandatory for a durable functional, esthetic and psychosomatic rehabilitation after ocular extirpation. PMID- 26160106 TI - [Ocular complications in a patient with dengue fever]. AB - This article presents the spontaneous development of ocular complications in a case of dengue fever in a young tourist returning from Thailand. Despite severe inital clinical symptoms, a clear remission occurred after several months without any therapy; however, a partial atrophy of the optic nerve remained. PMID- 26160107 TI - [Principles of glaucoma diagnostics with optical coherence tomography]. AB - BACKGROUND: In recent years many applications of optical coherence tomography (OCT) have led to a better understanding of glaucoma morphology. The clinical routine in the treatment of glaucoma is strongly influenced by the modern diagnostic aspects. METHODS: A selective search of the literature was carried out and the important aspects are presented taking own experiences into account. The measurement principles, diagnostic ability and pitfalls of the three OCT measurement procedures are highlighted. RESULTS: Retinal nerve fiber layer, macula and ganglion cell layer thickness as well as the minimum neuroretinal rim width have facilitated in particular the objective early diagnosis and follow-up measurements. CONCLUSION: For glaucoma, OCT measurements cannot replace the medical expert diagnosis but they represent a valuable decision-making aid for diagnostics and follow-up examinations. PMID- 26160108 TI - [In Process Citation]. PMID- 26160109 TI - Expression of a glucagon-like peptide-1 analogue, as a therapeutic agent for type II diabetes, with enhanced bioactivity and increased N-terminal homogeneity in Pichia pastoris. AB - OBJECTIVE: To improve the bioactivity and increase the N-terminal homogeneity of a glucagon-like peptide-1 (GLP-1) analogue expressed in Pichia pastoris. RESULTS: The GLP-1 analogue. GGH, consisting of two tandem mutant GLP-1 (GLP-1[A2G]) fused with the N-terminus of human serum albumin (HSA), was expressed in P. pastoris. We also designed and expressed the novel GLP-1 analogue NGGH, which had a His-tag fused with the N-terminus of GGH and an enterokinase (EK) cleavage site at the fusion junction. The His-tag was removed by EK digestion to yield GGH2, which was subsequently compared with GGH expressed in P. pastoris. The purification recovery of GGH2 was 35 % compared with 23 % for GGH. Furthermore, the bioactivity of GGH2 was 605 % higher than GGH, and N-terminal homogeneity was also improved. CONCLUSIONS: A simple method for the preparation of GGH2 with a cleavable His-tag was developed, and the resultant protein possessed improved bioactivity and N-terminal homogeneity. PMID- 26160110 TI - Recent advances in the use of gelatin in biomedical research. AB - The biomacromolecule, gelatin, has increasingly been used in biomedicine-beyond its traditional use in food and cosmetics. The appealing advantages of gelatin, such as its cell-adhesive structure, low cost, off-the-shelf availability, high biocompatibility, biodegradability and low immunogenicity, among others, have made it a desirable candidate for the development of biomaterials for tissue engineering and drug delivery. Gelatin can be formulated in the form of nanoparticles, employed as size-controllable porogen, adopted as surface coating agent and mixed with synthetic or natural biopolymers forming composite scaffolds. In this article, we review recent advances in the versatile applications of gelatin within biomedical context and attempt to draw upon its advantages and potential challenges. PMID- 26160111 TI - Dearomative [2 + 2] Cycloaddition and Formal C-H Insertion Reaction of o Carboryne with Indoles: Synthesis of Carborane-Functionalized Heterocycles. AB - o-Carboryne (1,2-dehydro-o-carborane) is a very useful synthon for the synthesis of a variety of carborane-functionalized heterocycles. Reaction of o-carboryne with N-protected indoles gave carborane-fused indolines if the protecting group was TMS via dearomative [2 + 2] cycloaddition or carboranyl indoles for N-alkyl ones through formal C-H insertion reaction. For N-aryl indoles, both reactions were observed, giving two products, in which the product ratio was dependent upon the nature of the substituents on the aryl rings. In general, electron withdrawing substituents favor [2 + 2] cycloaddition, whereas electron-donating substituents promote a formal C-H insertion pathway. This reaction is also compatible with other heteroaromatics. Thus, a stepwise reaction mechanism was proposed to account for the experimental observations. These protocols offer general and efficient methods for the preparation of carborane-functionalized indoles and indolines as well as other heterocycles. The observed dearomative [2 + 2] cycloaddition represents the first example of indoles to undergo such reaction in the absence of transition metals or without UV irradiation. All new compounds were fully characterized by (1)H, (13)C, and (11)B NMR spectroscopy as well as HRMS spectrometry. Some were further confirmed by single-crystal X-ray analyses. PMID- 26160112 TI - Imidazolidine-4-one derivatives in the search for novel chemosensitizers of Staphylococcus aureus MRSA: synthesis, biological evaluation and molecular modeling studies. AB - A series of amine derivatives of 5-aromatic imidazolidine-4-ones (7-19), representing three subgroups: piperazine derivatives of 5-arylideneimidazolones (7-13), piperazine derivatives of 5-arylideneimidazolidine-2,4-dione (14-16) and primary amines of 5-naphthyl-5-methylimidazolidine-2,4-diones (17-19), was evaluated for their ability to improve antibiotics effectiveness in two strains of Gram-positive Staphylococcus aureus: ATCC 25923 (a reference strain) and MRSA (methicillin resistant S. aureus) HEMSA 5 (a resistant clinical isolate). The latter compounds (17-19) were obtained by 4-step synthesis using Bucherer-Bergs condensation, two-phase bromoalkylation and Gabriel reactions. The naphthalen derivative: (Z)-5-(naphthalen-2-ylmethylene)-2-(piperazin-1-yl)-3H-imidazol-4(5H) one (10) was the most potent in combination with beta-lactam antibiotics and ciprofloxacin against the resistant strain. The high potency to increase efficacy of oxacillin was noted for (Z)-5-(anthracen-10-ylmethylene)-2-(piperazin-1-yl)-3H imidazol-4(5H)one (12) too. In order to explain the mechanism of action of the compounds 10 and 12, docking studies with the use of crystal structures of a penicillin binding protein (PBP2a) and MecR1 were carried out. Their outcomes suggested that the most probable mechanism of action of the active compounds is the interaction with MecR1. Molecular dynamic experiments performed for the active compounds and compound 13 (structurally similar to 12) supported this hypothesis and provided possible explanation of activity dependencies of the tested compounds in terms of the restoration of antibiotic efficacy in S. aureus MRSA HEMSA 5. PMID- 26160113 TI - Molecular docking design and one-pot expeditious synthesis of novel 2,5 diarylpyrazolo[1,5-a]pyrimidin-7-amines as anti-inflammatory agents. AB - A series of novel 2,5-diarylpyrazolo[1,5-a]pyrimidin-7-amines were designed as COX-2 inhibitors by molecular docking studies and their synthesis was accomplished via an expeditious one-pot reaction. Structures of the compounds were established by NMR ((1)H-(13)C), IR spectroscopy and high resolution mass spectrometry. All the eleven compounds have been screened for their in vivo anti inflammatory activity on rats by carrageenan-induced rat paw edema assay. Correlation studies of calculated moldock score and observed percentage inhibition have also been carried out which concluded that the synthesized 2,5 diarylpyrazolo[1,5-a]pyrimidin-7-amines act as potent anti-inflammatory agents up to the 4th hour of study. PMID- 26160114 TI - Probing the 'bipolar' nature of the carbonic anhydrase active site: aromatic sulfonamides containing 1,3-oxazol-5-yl moiety as picomolar inhibitors of cytosolic CA I and CA II isoforms. AB - A series of potent inhibitors of human carbonic anhydrase (CA) isoforms I and II has been prepared via a direct, chemoselective sulfochlorination of a range of 1,3-oxazolyl benzenes and thiophenes, followed by primary sulfonamide synthesis. The latter functionality is a known zinc-binding group (ZBG) responsible for anchoring the inhibitors to the CA's zinc metal ion. The compound's periphery as well as the overall scaffold geometry was designed to enable optimal interactions with the two distinct sides of the enzyme's active site, one of which is lined with hydrophobic residues and while the other is predominantly hydrophilic. As a result, several compounds inhibiting the therapeutically important cytosolic CA I and CA II in picomolar range have been identified. These compounds are one of the most potent CA inhibitors identified to-date. Not only the remarkable (>10 000 fold), cytosolic CA I and CA II selectivity vs. the membrane-bound CA IX and CA XII isoforms, but also the pronounced CA II/I selectivity observed in some cases, allow considering this series as a set of isoform-selective chemical biology tools and promising starting points for drug candidate development. PMID- 26160115 TI - Pyrene is a Novel Constitutive Androstane Receptor (CAR) Activator and Causes Hepatotoxicity by CAR. AB - Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous persistent environmental pollutants which are primarily formed from the incomplete combustion of organic materials. Many potential sources of human exposure to PAHs exist, including daily exposures from the ambient environment or occupational settings. PAHs have been found to cause harmful effects on human health. Here, we evaluated the adverse effects of pyrene, a common PAH, on the liver. The present study demonstrates that pyrene is able to activate mouse constitutive androstane receptor (CAR). CAR protein, as measured by Western blot analysis, was observed to translocate into the nucleus from the cytoplasm in mouse liver after exposure to pyrene. Utilizing CAR null mice, we identified that CAR mediates pyrene induced hepatotoxicity. Increased relative liver weight, hepatocellular hypertrophy, and elevated serum alanine aminotransferase levels were found in wild-type but not CAR null mice after orally administered pyrene. We further show that pyrene induced the expression of mouse liver metabolism enzymes including CYP2B10, CYP3A11, GSTm1, GSTm3, and SULT1A1, and caused hepatic glutathione depletion in wild-type but not CAR null mice. Moreover, by luciferase reporter assay and quantitative real-time PCR analysis, pyrene was found to be a potential inducer of CYP2B6 expression via activation of human CAR in HepG2 cells and human primary hepatocytes. Our observations suggest that pyrene is a novel CAR activator and that CAR is essential for mediating pyrene-induced liver injury. PMID- 26160116 TI - Determination of Toxic Activities in Bothrops spp. Snake Venoms Using Animal-Free Approaches: Correlation Between In Vitro Versus In Vivo Assays. AB - The main purpose of this study is to investigate the in vitro toxic effects of 5 Bothrops spp. snake venoms, which are part of the antigenic mixture used for the production of Brazilian antivenom, and evaluate their correlation with the in vivo toxic activities of Bothrops spp. venoms. The correlation analysis could be helpful for the replacement of living animals experimentation for in vitro bioassay. Cytotoxicity, L-amino acid oxidase (LAAO), proteolitic (serine and metalloproteinase), hyaluronidase (Hyal), and phospholipase A2 (PLA2) activities were estimated and the correlation coefficient was determined for each activity in relation to lethality, edema, hemorrhage and necrosis induced in live animals by B. jararaca, B. alternatus, B. jararacussu, B. neuwiedi, and B. moojeni venoms. The lethal activity in mice was highly related to Hyal activity (r = 0.94, p < .05), edema related to PLA2 activity (r = 0.94, p < .05), whereas the necrotizing activity showed high correlation with LAAO activity (r = 0.83, p < .05). A very significant correlation between in vitro cytotoxicity and LAAO activities was also observed (r = 0.97, p < .05). PMID- 26160118 TI - Unexpected in-situ Free Radical Generation and Catalysis to Ag/Polymer Nanocomposite. AB - In this study, we discover unexpectedly that simple reaction of AgNO3 with oleic acid (OA) without solvent and surfactant could generate alkyl free radical which can catalyze double-bond polymerization of OA to form 1D polymeric oleic acid (POA) chain. In certain conditions, these POA chains circumvolute tightly each other to form microspheres and micro-plates in which monodisperse 4-5 nm Ag nanoparticles (NPs) were absorbed. It has been revealed that alkyl free radical generated during the redox reaction of carboxyl group of OA with Ag(+) at relative low temperature. Then, the alkyl free radical catalyzed the double-bond polymerization of OA when the reaction temperature was further increased. Different from commonly-seen hydrophobic nanoparticles prepared in oleic acid based microemulsion system, the nanocomposites cannot dispersed in n-hexane and could dispersed in ethanol and THF. The unusual dispersion behavior has been explained in terms of their structure and polarity of POA chain. The method combines the nucleation of Ag nanoparticles and the polymerization of monomer in a facile one-pot reaction, which provides a novel way for metal-polymer microsphere nanocomposite with low-cost, easy-operation and high-yield. PMID- 26160117 TI - Comparative Proteomic Characterization of 4 Human Liver-Derived Single Cell Culture Models Reveals Significant Variation in the Capacity for Drug Disposition, Bioactivation, and Detoxication. AB - In vitro preclinical models for the assessment of drug-induced liver injury (DILI) are usually based on cryopreserved primary human hepatocytes (cPHH) or human hepatic tumor-derived cell lines; however, it is unclear how well such cell models reflect the normal function of liver cells. The physiological, pharmacological, and toxicological phenotyping of available cell-based systems is necessary in order to decide the testing purpose for which they are fit. We have therefore undertaken a global proteomic analysis of 3 human-derived hepatic cell lines (HepG2, Upcyte, and HepaRG) in comparison with cPHH with a focus on drug metabolizing enzymes and transport proteins (DMETs), as well as Nrf2-regulated proteins. In total, 4946 proteins were identified, of which 2722 proteins were common across all cell models, including 128 DMETs. Approximately 90% reduction in expression of cytochromes P450 was observed in HepG2 and Upcyte cells, and approximately 60% in HepaRG cells relative to cPHH. Drug transporter expression was also lower compared with cPHH with the exception of MRP3 and P-gp (MDR1) which appeared to be significantly expressed in HepaRG cells. In contrast, a high proportion of Nrf2-regulated proteins were more highly expressed in the cell lines compared with cPHH. The proteomic database derived here will provide a rational basis for the context-specific selection of the most appropriate 'hepatocyte-like' cell for the evaluation of particular cellular functions associated with DILI and, at the same time, assist in the construction of a testing paradigm which takes into account the in vivo disposition of a new drug. PMID- 26160119 TI - Biochemical and lysosomal biomarkers in the mussel Mytilus galloprovincialis from the Mar Piccolo of Taranto (Ionian Sea, Southern Italy). AB - Biomarkers are internationally recognized as useful tools in marine coastal biomonitoring, in particular, as early-warning signals at the level of individual organisms to assess biological effects of pollutants and other stressors. In the present study, Mytilus galloprovincialis has been employed as a sentinel organism to assess biological pollution effects in the Mar Piccolo of Taranto (Southern Italy), a coastal lagoon divided into two small inlets, connected to the open sea through one natural and one artificial narrow openings. Mussels were collected in June 2013 at three sites located within each of the two inlets of the Mar Piccolo. Biological effects were investigated through a suite of biomarkers suitable to reflect effects and/or exposure to contaminants at biochemical and cellular levels. Biochemical biomarkers included glutathione-S-transferase (GST) and acetylcholinesterase (AChE) enzyme activities; as histochemical biomarkers, lysosomal membrane stability, lipofuscin and neutral lipid accumulation, and lysosomal structural changes were considered. As a whole, results highlighted differences among the three study sites, particularly for GST, AChE, and lipofuscins, which are consistent with the variations of the chemical pollutants in sediments. The applied biomarkers showed that a stress syndrome likely to be ascribed to environmental pollutants is occurring in mussels living in the Mar Piccolo of Taranto, in particular, the ones inhabiting the first inlet. PMID- 26160120 TI - Adsorption characteristics of polycyclic aromatic hydrocarbons from non-aqueous media using activated carbon derived from phenol formaldehyde resin: kinetics and thermodynamic study. AB - Porous carbons were prepared by carbonization and activation of phenol formaldehyde resin by gasification with CO2 at 900 degrees C. Prepared activated carbon from phenol formaldehyde was characterized by measuring thermogravimetry (TG), differential thermal analysis (DTA), pH, surface area, porosity, and pore size distribution. The specific surface area (SSA) of these carbons ranges from 562 to 1904 m2/g, while their point of zero charge (pHPZC) varies from 2.6 to 8.8. The ability of the prepared activated carbon by gasification with CO2 at 900 degrees C from phenol formaldehyde resin (PFAC) to remove a series of polycyclic aromatic hydrocarbons (PAHs), e.g., naphthalene, fluorene, phenanthrene, pyrene, and fluoranthene, from mixtures of organic solvents with different polarities and chemical structures was tested. The adsorption capacity increases with the increasing the SSA and pHPZC of the carbons, confirming the roles of dispersive interactions. The kinetics and thermodynamics of the adsorption of phenanthrene as a model compound of PAH on PFAC in the organic solvent were studied. The adsorption capacity became notably greater with an increase in contact time and initial phenanthrene concentration. PMID- 26160121 TI - Microbial community analysis in a combined anaerobic and aerobic digestion system for treatment of cellulosic ethanol production wastewater. AB - This study investigated the microbial diversity established in a combined system composed of a continuous stirred tank reactor (CSTR), expanded granular sludge bed (EGSB) reactor, and sequencing batch reactor (SBR) for treatment of cellulosic ethanol production wastewater. Excellent wastewater treatment performance was obtained in the combined system, which showed a high chemical oxygen demand removal efficiency of 95.8% and completely eliminated most complex organics revealed by gas chromatography-mass spectrometry (GC-MS). Denaturing gradient gel electrophoresis (DGGE) analysis revealed differences in the microbial community structures of the three reactors. Further identification of the microbial populations suggested that the presence of Lactobacillus and Prevotella in CSTR played an active role in the production of volatile fatty acids (VFAs). The most diverse microorganisms with analogous distribution patterns of different layers were observed in the EGSB reactor, and bacteria affiliated with Firmicutes, Synergistetes, and Thermotogae were associated with production of acetate and carbon dioxide/hydrogen, while all acetoclastic methanogens identified belonged to Methanosaetaceae. Overall, microorganisms associated with the ability to degrade cellulose, hemicellulose, and other biomass-derived organic carbons were observed in the combined system. The results presented herein will facilitate the development of an improved cellulosic ethanol production wastewater treatment system. PMID- 26160122 TI - Modeling the binding affinity of structurally diverse industrial chemicals to carbon using the artificial intelligence approaches. AB - Binding affinity of chemical to carbon is an important characteristic as it finds vast industrial applications. Experimental determination of the adsorption capacity of diverse chemicals onto carbon is both time and resource intensive, and development of computational approaches has widely been advocated. In this study, artificial intelligence (AI)-based ten different qualitative and quantitative structure-property relationship (QSPR) models (MLPN, RBFN, PNN/GRNN, CCN, SVM, GEP, GMDH, SDT, DTF, DTB) were established for the prediction of the adsorption capacity of structurally diverse chemicals to activated carbon following the OECD guidelines. Structural diversity of the chemicals and nonlinear dependence in the data were evaluated using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. The generalization and prediction abilities of the constructed models were established through rigorous internal and external validation procedures performed employing a wide series of statistical checks. In complete dataset, the qualitative models rendered classification accuracies between 97.04 and 99.93%, while the quantitative models yielded correlation (R(2)) values of 0.877-0.977 between the measured and the predicted endpoint values. The quantitative prediction accuracies for the higher molecular weight (MW) compounds (class 4) were relatively better than those for the low MW compounds. Both in the qualitative and quantitative models, the Polarizability was the most influential descriptor. Structural alerts responsible for the extreme adsorption behavior of the compounds were identified. Higher number of carbon and presence of higher halogens in a molecule rendered higher binding affinity. Proposed QSPR models performed well and outperformed the previous reports. A relatively better performance of the ensemble learning models (DTF, DTB) may be attributed to the strengths of the bagging and boosting algorithms which enhance the predictive accuracies. The proposed AI models can be useful tools in screening the chemicals for their binding affinities toward carbon for their safe management. PMID- 26160123 TI - Treatment of pollution in constructed wetlands: from the fundamental mechanisms to the full-scale applications. PMID- 26160124 TI - Organochlorine pesticides and parasites in Mugil incilis collected in Cartagena Bay, Colombia. AB - Nematode parasites of the Anisakides family are often found in people living in countries where fish is consumed raw or partially cooked. This research shows the histological changes in the liver and spleen of Mugil incilis, collected in Cartagena Bay. These changes are associated with pollution by organochlorine pesticides and their possible influence on the parasite. Organochlorine compounds were extracted using the headspace-solid-phase microextraction (HS-SPME) technique. Residual amounts in the muscle of M. incilis such as beta-HCH, gamma HCH, heptachlor, aldrin, endosulfan, 4,4'-DDE, and dieldrin, among others, were identified by gas chromatography connected to an electron capture detector, indicating that the fauna of Cartagena Bay are exposed to these pollutants. Histological analysis was carried out on liver and spleen samples of M. incilis which were fixed, processed, and embedded in paraffin. The presence of melano macrophages, granulomes, and trematodes in the liver was the most important changes observed. Larval prevalence for the Anisakis spp. was determined to be 1.6%; for Pseudoterranova spp., 25.3%, and for Contracaecum spp., 57.8%. Other parasites such as acanthocephalans were also reported for a total of 15.3%. Nevertheless, no significant correlation between parasites and organochlorines was found. This study is the first to correlate the presence of organochlorine compounds and histological damage in the liver and spleen of M. incilis, with the presence of parasites in fish from Cartagena Bay (Colombia). PMID- 26160125 TI - Mercury species accumulation and trophic transfer in biological systems using the Almaden mining district (Ciudad Real, Spain) as a case of study. AB - The impact of mercury (Hg) pollution in the terrestrial environments and the terrestrial food chains including the impact on human food consumption is still greatly under-investigated. In particular, studies including Hg speciation and detoxification strategies in terrestrial animals are almost non-existing, but these are key information with important implications for human beings. Therefore, in this work, we report on Hg species (inorganic mercury, iHg, and monomethylmercury, MeHg) distribution among terrestrial animal tissues obtained from a real-world Hg exposure scenario (Almaden mining district, Spain). Thus, we studied Hg species (iHg and MeHg) and total selenium (Se) content in liver and kidney of red deer (Cervus elaphus; n = 41) and wild boar (Sus scrofa; n = 16). Similar mercury species distribution was found for both red deer and wild boar. Major differences were found between tissues; thus, in kidney, iHg was clearly the predominant species (more than 81%), while in liver, the species distribution was less homogeneous with a percentage of MeHg up to 46% in some cases. Therefore, Hg accumulation and MeHg transfer were evident in terrestrial ecosystems. The interaction between total Se and Hg species has been evaluated by tissue and by animal species. Similar relationships were found in kidney for both Hg species in red deer and wild boar. However, in liver, there were differences between animals. The possible underlying mechanisms are discussed. PMID- 26160126 TI - Potential of Opuntia ficus-indica for air pollution biomonitoring: a lead isotopic study. AB - Opuntia ficus-indica (Ofi) is a long-domesticated cactus that is widespread throughout arid and semiarid regions. Ofi is grown for both its fruits and edible cladodes, which are flattened photosynthetic stems. Young cladodes develop from mother cladodes, thus forming series of cladodes of different ages. Therefore, successive cladodes may hold some potential for biomonitoring over several years the local atmospheric pollution. In this study, cladodes, roots, dust deposited onto the cladodes, and soil samples were collected in the vicinity of three heavily polluted sites, i.e., a fertilizer industry, the road side of a highway, and mine tailings. The lead content was analyzed using atomic absorption spectroscopy (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS). Scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX) was used to characterize the cladode surfaces and the nature of dust deposit, and the lead isotopes were analyzed to identify the origin of Pb. The results show that (i) Ofi readily bioaccumulates Pb, (ii) the lead isotopic composition of cladodes evidences a foliar pathway of lead into Ofi and identifies the relative contributions of local Pb sources, and (iii) an evolution of air quality is recorded with successive cladodes, which makes Ofi a potential biomonitor to be used in environmental and health studies. PMID- 26160127 TI - Multidetector CT diagnosis of massive hemobilia due to gallbladder polyposis in a child with metachromatic leukodystrophy. AB - Hemobilia secondary to gallbladder polyposis is rare in children but has been reported in a few children with metachromatic leukodystrophy. We present a case with preoperative multidetector computed tomography (MDCT) diagnosis of massive hemobilia caused by gallbladder polyposis in a patient with metachromatic leukodystrophy. Our report highlights the importance of both awareness of the association of gallbladder polyposis with other syndromes such as metachromatic leukodystrophy as well as the possibility of this entity presenting with life threatening bleeding. PMID- 26160128 TI - [Epileptic seizure-induced vertebral body fractures]. AB - In the literature epilepsy is described as the most common cause of generalized seizures. Vertebral body fractures are a rare complication of epileptic convulsions, occurring with an incidence of 3%. We present the case of a 37-year old healthy patient, who sustained contiguous fractures of the thoracic and lumbar spine during the first manifestation of epilepsy with primary localized and then secondary generalized epileptic seizures. A complication-free outcome was achieved with a combination of conservative and operative therapies. PMID- 26160129 TI - [Essential measures for prehospital treatment of severely injured patients: The trauma care bundle]. AB - BACKGROUND: In order to ensure adequate treatment and to avoid complications, care bundles are increasingly being implemented. These are comprehensive and evidence-based procedures for the treatment of individual diseases or injuries which should be carried out for every patient. The aim of this study was to define a care bundle for the prehospital treatment of severely injured patients. MATERIAL AND METHODS: The scientific contents of the bundle were gathered from the interdisciplinary evidence-based S3 guidelines for the treatment of severely injured patients by the German Trauma Society. The ABCDE scheme suggested by the prehospital trauma life support (PHTLS(r)) and the advanced trauma life support (ATLS(r)) functioned as a matrix for the individual elements in the bundles. The identified elements were finalized by a consensus process. RESULTS AND DISCUSSION: A bundle of six elements was suggested and a comprehensive summary of key items during prehospital management of severely injured patients was identified. In a next step the effectiveness of the care bundle should be evaluated in a clinical trial. PMID- 26160130 TI - The Nonwhite Woman Surgeon: A Rare Species. AB - BACKGROUND: As of 2012, 39% of medical student graduates were nonwhite, yet very few nonwhite women graduates chose to become surgeons. METHODS: To better understand issues regarding nonwhite women in surgery, an online survey was sent to surgeons across the United States. Results are based on self-reported data. Mean data are reported. RESULTS: A total of 194 surgeons (42% women) completed the survey; only 12% of responders were nonwhite. Overall, 56% of nonwhite women felt they earned less than what men surgeons earn for equal work. Nonwhite women surgeons earned less than what men surgeons ($224,000 vs. 351,000, p < 0.00002) and white women surgeons ($285,000, p = 0.02) earned. Overall, 96% of nonwhite surgeons believed that racial discrimination currently exists among surgeons. CONCLUSIONS: The few nonwhite women surgeons in the United States recognize that they are paid significantly less than what other surgeons are paid. Inequitable remuneration and a discriminatory work environment encountered by nonwhite women surgeons must be addressed. PMID- 26160131 TI - A Structured Educational Curriculum Including Online Training Positively Impacts American Board of Surgery In-Training Examination Scores. AB - OBJECTIVE: To assess the effect of a structured postgraduate year 1 educational curriculum, including online surgical training, on American Board of Surgery In Training Examination (ABSITE) scores. DESIGN: This was a retrospective cohort study. SETTING: The study was performed in an academic surgical residency program in a tertiary care hospital, Cleveland Clinic Foundation, Cleveland, Ohio. PARTICIPANTS: The participants were 140 surgical postgraduate year 1 residents from 2000 to 2009. Interns from 2000 to 2004 were grouped together and completed a self-directed learning curriculum. Interns from 2005 to 2009 participated in a structured educational curriculum that included lectures and the use of an online program. Lectures were based on the American College of Surgeons curriculum. The online program consisted of 8 to 12 hours of assigned tutorials and quizzes that corresponded to the lectures and 3 multiple-choice (MC) examinations. RESULTS: Use of a structured educational curriculum led to improved ABSITE scores (66 +/- 9%) compared with that of those who had no curriculum (55 +/- 10%, p < 0.001). Several variables positively correlated with the ABSITE score: United States Medical Licensing Examination step 1 score (p < 0.001), monthly quiz scores (p = 0.003), average MC examination scores (p = 0.005), lecture attendance (p = 0.02), and time spent online (p = 0.04). Multivariable analysis demonstrated that the step 1 United States Medical Licensing Examination score, time spent online, and MC examination score are predictive of total the ABSITE score. When ABSITE subscores (basic science and clinical science) were compared, the online curriculum had a greater effect on basic science subscores, whereas lectures had a greater effect on clinical science subscores. CONCLUSIONS: Providing surgery residents a structured curriculum with lectures and an online component positively impacts ABSITE scores. PMID- 26160132 TI - How do Perceptions of Autonomy Differ in General Surgery Training Between Faculty, Senior Residents, Hospital Administrators, and the General Public? A Multi-Institutional Study. AB - OBJECTIVE: Identify barriers to resident autonomy in today's educational environment as perceived through 4 selected groups: senior surgical residents, teaching faculty, hospital administration, and the general public. DESIGN: Anonymous surveys were created and distributed to senior residents, faculty, and hospital administrators working within 3 residency programs. The opinions of a convenience sample of the general public were also assessed using a similar survey. SETTING: Keesler Medical Center, Keesler AFB, MS; the University of Texas Health Science of San Antonio, TX; and the University of Nebraska Medical Center, Omaha, NE. PARTICIPANTS: A total of 169 responses were collected: 32 residents, 50 faculty, 20 administrators, and 67 general public. RESULTS: Faculty and residents agree that when attending staff grant more autonomy, residents' self confidence and sense of ownership improve. Faculty felt that residents should have less autonomy than residents did (p < 0.001). When asked to reflect on the current level of autonomy at their institution, 47% of residents felt that they had too little autonomy and 38% of faculty agreed. No resident or faculty felt that residents had too much autonomy at their institution. The general public were more welcoming of resident participation than faculty (p = 0.002) and administrators (p = 0.02) predicted they would be. When the general public were asked regarding their opinions about resident participation with complex procedures, they were less welcoming than faculty, administrators, and residents thought (p < 0.001). The general public were less likely to think that resident involvement would improve their quality of care (p < 0.001). CONCLUSION: Faculty and senior residents both endorse resident autonomy as important for resident development. The general public are more receptive to resident participation than anticipated. However, with increasing procedural complexity and resident independence, they were less inclined to have residents involved. The general public also had more concerns regarding quality of care provided by residents than the other groups had. PMID- 26160133 TI - The component group structure of DPPC bilayers obtained by specular neutron reflectometry. AB - Specular neutron reflectometry was measured on a floating bilayer system consisting of 1,2-dipalmitoyl-d62-sn-glycero-3-phosphocholine deposited over a 1,2-dibehenoyl-sn-glycero-3-phosphocholine bilayer at 25 and 55 degrees C. The internal structure of lipid bilayers was described by a one-dimensional neutron scattering length density profile model, originally developed for the evaluation of small-angle scattering data. The reflectivity data from the supported bilayer were evaluated separately and used further as constraints in modeling the floating bilayer reflectivity curves. The model reflectivity curves successfully describe the experimental reflectivities of the supported bilayer in the gel phase and the floating bilayer system in the liquid-crystalline phase. The results yield an internal structure of a deposited bilayer and a floating bilayer on the level of component groups of lipid molecules. The obtained structure of the floating d62-diC16:0PC bilayer displays high resemblance of the bilayer structure in the form of unilamellar vesicles. At the same time, however, the results show differences in comparison to unilamellar vesicle bilayers, most likely due to the undulations of supported bilayers. PMID- 26160134 TI - Functional Network Analysis Reveals Versatile MicroRNAs in Human Heart. AB - BACKGROUND: Acting on many mRNAs allows the power of a single miRNA to modulate multiple pathophysiological phenotypes. One question is whether versatile miRNAs exist in the pathological scenarios of myocardial infarction (MI) and heart failure (HF). METHODS: A hypergeometric analysis, in combination with network based functional analyses, was performed on the available human protein interaction and miRNA-gene association data to highlight versatile miRNAs among the significantly dysregulated miRNAs in MI and HF. In vivo, mice models of MI and HF were then established to investigate whether dysregulated expression be undertaken by versatile miRNA identified here. RESULTS: Systematic analyses really identified the previously validated miRNAs that have been verified of multiple important roles in MI and HF, demonstrating method effectiveness. By using this means, we innovatively revealed the vital role of miR-7 in maintaining the dynamic balance of protein interactions and its obvious overexpression in MI and HF that implies pathological involvement. Functional experiments are definitely needed for further revealing its potential influences on MI- or HF-led myocardial injury. CONCLUSION: Our results have implications not only for the coming miRNA-based strategy in treating MI and HF but also for further understanding on gene regulation by miRNAs in human heart. PMID- 26160135 TI - ESE guidelines, why and how. PMID- 26160136 TI - European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults. AB - Hypoparathyroidism (HypoPT) is a rare (orphan) endocrine disease with low calcium and inappropriately low (insufficient) circulating parathyroid hormone levels, most often in adults secondary to thyroid surgery. Standard treatment is activated vitamin D analogues and calcium supplementation and not replacement of the lacking hormone, as in other hormonal deficiency states. The purpose of this guideline is to provide clinicians with guidance on the treatment and monitoring of chronic HypoPT in adults who do not have end-stage renal disease. We intend to draft a practical guideline, focusing on operationalized recommendations deemed to be useful in the daily management of patients. This guideline was developed and solely sponsored by The European Society of Endocrinology, supported by CBO (Dutch Institute for Health Care Improvement) and based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) principles as a methodological base. The clinical question on which the systematic literature search was based and for which available evidence was synthesized was: what is the best treatment for adult patients with chronic HypoPT? This systematic search found 1100 articles, which was reduced to 312 based on title and abstract. The working group assessed these for eligibility in more detail, and 32 full-text articles were assessed. For the final recommendations, other literature was also taken into account. Little evidence is available on how best to treat HypoPT. Data on quality of life and the risk of complications have just started to emerge, and clinical trials on how to optimize therapy are essentially non existent. Most studies are of limited sample size, hampering firm conclusions. No studies are available relating target calcium levels with clinically relevant endpoints. Hence it is not possible to formulate recommendations based on strict evidence. This guideline is therefore mainly based on how patients are managed in clinical practice, as reported in small case series and based on the experiences of the authors. PMID- 26160137 TI - Examining the relationship between skilled music training and attention. AB - While many aspects of cognition have been investigated in relation to skilled music training, surprisingly little work has examined the connection between music training and attentional abilities. The present study investigated the performance of skilled musicians on cognitively demanding sustained attention tasks, measuring both temporal and visual discrimination over a prolonged duration. Participants with extensive formal music training were found to have superior performance on a temporal discrimination task, but not a visual discrimination task, compared to participants with no music training. In addition, no differences were found between groups in vigilance decrement in either type of task. Although no differences were evident in vigilance per se, the results indicate that performance in an attention-demanding temporal discrimination task was superior in individuals with extensive music training. We speculate that this basic cognitive ability may contribute to advantages that musicians show in other cognitive measures. PMID- 26160138 TI - Oxidative Heterocycle Formation Using Hypervalent Iodine(III) Reagents. AB - Hypervalent iodine(III) reagents have been widely exploited in a diverse array of synthetic transformations. This chapter focuses on the general application of hypervalent iodine(III) reagents in the de novo synthesis and in the late stage functionalization of heterocyclic compounds. PMID- 26160139 TI - Relationship between Nitrate-Induced Headache and Coronary Artery Lesion Complexity. AB - OBJECTIVE: The aim of the present study was to investigate the association between nitrate-induced headache (NIH) and the complexity of coronary artery lesions in patients with stable coronary artery disease (CAD). SUBJECTS AND METHODS: Two hundred and seventy-five patients with anginal chest pain who underwent coronary angiography were enrolled in the present study. NIH was defined as the presence of headache due to nitrate treatment (isosorbide mononitrate 40 mg) after excluding confounding factors. Coronary artery lesion complexity was assessed by the SYNTAX score (SXscore) using a dedicated computer software system. RESULTS: The mean SXscore was lower in the patients with NIH than in patients without NIH (7.3 +/- 5.2 vs. 14.4 +/- 8.5, respectively; p < 0.001). Additionally, patients with NIH had a lower rate of multivessel disease compared with those without NIH (the mean number of diseased vessels was 1.5 +/- 0.7 and 2.0 +/- 07, respectively; p < 0.001). In multivariate analysis, increasing age (p = 0.02) and headache (p = 0.001) were found to be independent determinants of SXscore. CONCLUSION: The present study demonstrated an independent inverse association between NIH and SXscore. The NIH could provide important predictive information about coronary artery lesion complexity in patients with stable CAD. PMID- 26160140 TI - [Serum procalcitonin: a reliable tool for the diagnosis and follow-up of neonatal bacterial infections in Sub-Saharan Africa]. AB - BACKGROUND AND AIM: Neonatal infection (NNI) is a public health problem in developing countries where pediatricians and specifically neonatologists encounter many diagnostic difficulties. Having a precise and easily measurable biological marker, with a high sensitivity and a high negative predictive value, that can rapidly detect NNI, remains a great challenge. The aim of this study was to determine the place of serum procalcitonin (PCT) in the diagnosis and follow up of bacterial NNI in resource-limited contexts. METHODS: We carried out a cross sectional study from October 2009 to February 2010 at the Mother and Child Centre of the Chantal Biya Foundation, Cameroon. We included all neonates born at term, suspected of NNI, and hospitalized in the Neonatal Care Unit of the aforementioned centre during the study period. We measured PCT levels at entry and 48h later, and determined its sensitivity, specificity, and positive and negative predictive values. RESULTS: Twenty-five out of the 98 neonates enrolled presented with a confirmed diagnosis of NNI. PCT was positive in 92.4% of cases. Contrariwise, serum C-reactive protein was positive in 84.6% of patients with a cut-off point at 6mg/L, and remained positive in only 38.4% of cases when the cut off point was raised to 20mg/L. The sensitivity, specificity, and positive and negative predictive values of PCT were 96.0%, 77.7%, 85.3%, and 93.3%, respectively. Six deaths were recorded, five of which exhibited very high PCT levels (>=10ng/mL). All neonates with negative PCT levels had a good clinical outcome as none of them died. If PCT were to be considered as a diagnostic tool of NNI, only 43 (43.9%) neonates would have benefited from a justified antibiotic therapy exceeding 48h, with a significant reduction in duration of hospitalization (9.1+/-3.3 vs 5.1+/-4.6 days; P<0.05). CONCLUSION: PCT may be an early and reliable indicator of bacterial NNI. Its course throughout hospitalization may reflect the therapeutic response, and elevated levels of PCT may be highly suggestive of a poor clinical prognosis. PCT could therefore serve as a useful tool for the screening, diagnosis, and follow-up of neonates suspected of bacterial NNI in resource-poor settings. PMID- 26160142 TI - Early and late event-related potentials are modulated by infant and adult faces of high and low attractiveness. AB - The processing of infant faces may be somewhat distinct from that of adult faces. Indeed, recent neuroimaging studies have provided evidence of an early, "baby specific" neural response whereby infant faces are perceived more rapidly than adult faces. Using event-related potentials, the present study aimed to determine whether the preferential response to infant faces is present at both early and late stages of face processing, and to investigate the effects of esthetic appearance on the processing of adult and infant faces by directly manipulating the perceived attractiveness or cuteness within a given face identity. Here, we find evidence for enhanced processing of infant faces, relative to adult faces, at both early (N170, P2) and late (LPC) stages of face processing. We also find that the esthetic appearance of both infant and adult faces modulates early neural responses, with enhanced responses to less attractive/cute faces as compared to more attractive/cute faces. Overall, our results provide additional evidence for a preferential response to infant faces at early stages of processing, and provide new evidence that this preferential response occurs at later stages of face processing as well, independent of the esthetic quality of the face or observer sex. PMID- 26160143 TI - Distance and proximity: research on social media connections in the field of communication disability. PMID- 26160144 TI - Novel synthesis and initial preclinical evaluation of (18)F-[FDG] labeled rhodamine: a potential PET myocardial perfusion imaging agent. AB - Myocardial perfusion imaging is one of the most commonly performed investigations in nuclear medicine studies. Due to the clinical importance of [(18)F]-fluoro-2 deoxy-D-glucose ([(18)F]-FDG) and its availability in almost every PET center, a new radiofluorinated [(18)F]-FDG-rhodamine conjugate was synthesized using [(18)F]-FDG as a prosthetic group. In a convenient and simple one-step radiosynthesis, [(18)F]-FDG-rhodamine conjugate was prepared in quantitative radiochemical yields, with total synthesis time of nearly 20 min and radiochemical purity of greater than 98%, without the need for HPLC purification, which make these approaches amenable for automation. Biodistribution studies in normal rats at 60 min post-injection demonstrated a high uptake in the heart (>11% ID/g) and favorable pharmacokinetics. Additionally, [(18)F]-FDG-rhodamine showed an extraction value of 27.63%+/-5.12% in rat hearts. These results demonstrate that [(18)F]-FDG-rhodamine conjugate may be useful as an imaging agent for the positron emission tomography evaluation of myocardial perfusion. PMID- 26160145 TI - Senile Dementia from Neuroscientific and Islamic Perspectives. AB - Diseases involving the nervous system drastically change lives of victims and commonly increase dependency on others. This paper focuses on senile dementia from both the neuroscientific and Islamic perspectives, with special emphasis on the integration of ideas between the two different disciplines. This would enable effective implementation of strategies to address issues involving this disease across different cultures, especially among the world-wide Muslim communities. In addition, certain incongruence ideas on similar issues can be understood better. The former perspective is molded according to conventional modern science, while the latter on the analysis of various texts including the holy Qur'an, sunnah [sayings and actions of the Islamic prophet, Muhammad (pbuh)] and writings of Islamic scholars. Emphasis is particularly given on causes, symptoms, treatments and prevention of dementia. PMID- 26160146 TI - Understanding the Irony: Canadian Gay Men Living with HIV/AIDS, Their Catholic Devotion, and Greater Well-being. AB - Nine Canadian Catholic HIV-positive gay men were interviewed to obtain a better understanding of why and how they were able to persevere in their faith despite their religion's teachings against homosexuality and contributions to the stigmatization of HIV/AIDS. By examining the lived experiences and personal perspectives of the participants, the study aimed to explore and elucidate the significant role of Catholicism and the Catholic Church both as a continued source of marginalization and oppression, as well as strength and support, for Canadian gay men living with HIV/AIDS today. PMID- 26160147 TI - The Role of Ghrelin in Senescence: A Mini-Review. AB - Ghrelin, a 28-amino acid hormone produced mainly by the X/A-like endocrine cells in gastric mucosa, has a widespread tissue distribution and diverse physiological functions such as hormonal, orexigenic, metabolic, cardiovascular, neurological, and immunological activities. Considerable evidence has suggested that ghrelin plays an important role in organism senescence or aging. The present review provides a comprehensive picture of this new development. We first reviewed the aging (senescence)-dependent reduction of ghrelin signaling, and then highlighted its relationship with the aging-associated alteration in food intake, energy metabolism, cardiovascular function, neurological activity, and adaptive immunity. Our literature review suggests that ghrelin is an innovative and promising agent in the treatment of these pathophysiological conditions associated with senescence. PMID- 26160148 TI - An analysis of application of health informatics in Traditional Medicine: A review of four Traditional Medicine Systems. AB - OBJECTIVE: This paper shall first investigate the informatics areas and applications of the four Traditional Medicine systems - Traditional Chinese Medicine (TCM), Ayurveda, Traditional Arabic and Islamic Medicine and Traditional Malay Medicine. Then, this paper shall examine the national informatics infrastructure initiatives in the four respective countries that support the Traditional Medicine systems. Challenges of implementing informatics in Traditional Medicine Systems shall also be discussed. METHODS: The literature was sourced from four databases: Ebsco Host, IEEE Explore, Proquest and Google scholar. The search term used was "Traditional Medicine", "informatics", "informatics infrastructure", "traditional Chinese medicine", "Ayurveda", "traditional Arabic and Islamic medicine", and "traditional malay medicine". A combination of the search terms above was also executed to enhance the searching process. A search was also conducted in Google to identify miscellaneous books, publications, and organization websites using the same terms. RESULTS: Amongst major advancements in TCM and Ayurveda are bioinformatics, development of Traditional Medicine databases for decision system support, data mining and image processing. Traditional Chinese Medicine differentiates itself from other Traditional Medicine systems with documented ISO Standards to support the standardization of TCM. Informatics applications in Traditional Arabic and Islamic Medicine are mostly ehealth applications that focus more on spiritual healing, Islamic obligations and prophetic traditions. Literature regarding development of health informatics to support Traditional Malay Medicine is still insufficient. Major informatics infrastructure that is common in China and India are automated insurance payment systems for Traditional Medicine treatment. National informatics infrastructure in Middle East and Malaysia mainly cater for modern medicine. Other infrastructure such as telemedicine and hospital information systems focus its implementation in modern medicine or are not implemented and strategized at a national level to support Traditional Medicine. CONCLUSION: Informatics may not be able to address all the emerging areas of Traditional Medicine because the concepts in Traditional Medicine system of medicine are different from modern system, though the aim may be same, i.e., to give relief to the patient. Thus, there is a need to synthesize Traditional Medicine systems and informatics with involvements from modern system of medicine. Future research works may include filling the gaps of informatics areas and integrate national informatics infrastructure with established Traditional Medicine systems. PMID- 26160149 TI - A self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy: a randomised controlled trial (the SELF study). AB - OBJECTIVES: To evaluate the clinical effectiveness of a self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy. DESIGN: Multi-centre pragmatic unblinded parallel group randomised controlled trial. SETTING: UK National Health Service. PARTICIPANTS: Patients with a clinical diagnosis of rotator cuff tendinopathy. INTERVENTIONS: The intervention was a programme of self-managed exercise prescribed by a physiotherapist in relation to the most symptomatic shoulder movement. The control group received usual physiotherapy treatment. MAIN OUTCOME MEASURES: The primary outcome measure was the Shoulder Pain & Disability Index (SPADI) at three months. Secondary outcomes included the SPADI at six and twelve months. RESULTS: A total of 86 patients (self-managed loaded exercise n=42; usual physiotherapy n=44) were randomised. Twenty-six patients were excluded from the analysis because of lack of primary outcome data at the 3 months follow-up, leaving 60 (n=27; n=33) patients for intention to treat analysis. For the primary outcome, the mean SPADI score at three months was 32.4 (SD 20.2) for the self-managed group, and 30.7 (SD 19.7) for the usual physiotherapy treatment group; mean difference adjusted for baseline score: 3.2 (95% Confidence interval -6.0 to +12.4 P = 0.49).By six and twelve months there remained no significant difference between the groups. CONCLUSIONS: This study does not provide sufficient evidence of superiority of one intervention over the other in the short-, mid- or long term and hence a self-management programme based around a single exercise appears comparable to usual physiotherapy treatment. PMID- 26160150 TI - SPAK Sensitive Regulation of the Epithelial Na Channel ENaC. AB - BACKGROUND/AIMS: The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na(+),K(+),2Cl(-) cotransport and thus renal salt excretion. The present study explored whether SPAK has similarly the potential to regulate the epithelial Na(+) channel (ENaC). METHODS: ENaC was expressed in Xenopus oocytes with or without additional expression of wild type SPAK, constitutively active (T233E)SPAK, WNK insensitive (T233A)SPAK or catalytically inactive (D212A)SPAK, and ENaC activity estimated from amiloride (50 uM) sensitive current (Iamil) in dual electrode voltage clamp experiments. Moreover, Ussing chamber was employed to determine Iamil in colonic tissue from wild type mice (spak(wt/wt)) and from gene targeted mice carrying WNK insensitive SPAK (spak(tg/tg)). RESULTS: Iamil was observed in ENaC-expressing oocytes, but not in water-injected oocytes. In ENaC expressing oocytes Iamil was significantly increased following coexpression of wild-type SPAK and (T233E)SPAK, but not following coexpression of (T233A)SPAK or (D212A)SPAK. Colonic Iamil was significantly higher in spak(wt/wt) than in spak(tg/tg) mice. CONCLUSION: SPAK has the potential to up-regulate ENaC. PMID- 26160151 TI - Histopathological Study of a Mummified Eye and Optic Nerve from a Strangled Peruvian Mummy. AB - We present the histopathological findings of a naturally mummified eye from the Peruvian Lambayeque culture (900-1,200 AD), in which rehydration, light microscopy, and scanning electron microscopy allowed a detailed analysis of several eye tissues including the eyelids, sclera, and optic nerve, the latter showing evidence of hemorrhage likely related to the documented strangulation as the cause of death. We conclude that histopathological analysis of rehydrated mummified tissues can provide valuable information from fragile eye structures including the optic nerve, and these findings can be useful from a forensic point of view. PMID- 26160152 TI - Identification and Functional Characterization of Two Novel Nonsense Mutations in the beta-Subunit of INSR That Cause Severe Insulin Resistance Syndrome. AB - BACKGROUND/AIMS: Donohue syndrome is an extremely rare autosomal recessive disorder caused by mutations in INSR. This study describes the clinical course of a patient with Donohue syndrome, and we also evaluated the molecular and functional characteristics of 2 novel INSR mutations. METHODS: Our patient was a male newborn with acanthosis nigricans, lack of subcutaneous fat, hirsutism, thick lips, and high serum insulin levels, all of which are characteristic of Donohue syndrome. INSR mutation analysis was performed, and Western blot analysis was used to verify the effects of the novel mutations on INSR protein expression. RESULTS: Direct INSR sequencing identified the following 2 novel compound heterozygous mutations in the beta-subunit of INSR: p.Arg1066* and p.Gln1232*. Western blot analysis of skin fibroblasts revealed a comparable expression of the alpha-subunit of INSR in mutant and control samples, but reduced levels of mature INSR beta-subunit protein were found in mutant INSR-expressing cells in comparison to the controls. CONCLUSIONS: This study describes the clinical course of a male patient with Donohue syndrome and the molecular characteristics of 2 novel compound heterozygous mutations in INSR. These novel nonsense mutations are associated with reduced expression of the mature INSR beta-subunit, which was most likely due to impaired proreceptor processing. PMID- 26160153 TI - An increase in joy after two weeks is more specific of later antidepressant response than a decrease in sadness. AB - BACKGROUND: Early improvement in positive emotions-more than decreases in negative emotions-was highly predictive of treatment response in an ecologically valid prospective manner. This result needs replication with simpler assessments to determine whether it can be translated into clinical practice. METHODS: 2049 adult depressed outpatients receiving agomelatine were assessed at inclusion, week 2, and week 6 using the clinician-rated Quick Inventory of Depressive Symptomatology, Sheehan Disability Scale, Clinical Global Impression scale, and Multidimensional Assessment of Thymic States (MATHYS), an auto-questionnaire rating the frequency of emotions, including sadness and joy, over the previous week. RESULTS: Joy and sadness had a relatively low correlation coefficient at baseline (r=-0.277), joy (r=-0.160) being less correlated with clinical severity than sadness (r=0.317). An increase in joy at week 2 had higher specificity (85.04%) and positive predictive value (70.55%) for treatment response than decreased sadness (57.92% and 66.04%, respectively), and the global capacity of the former to predict remission, either clinical (Yule Q coefficient, 39.96%) or functional (44.35%), was even better compared to the prediction of clinical response (37.38%). LIMITATIONS: MATHYS retrospectively assesses emotions, with five possible ratings only, relying on self-rated frequencies. With only a 6-week follow-up, conclusions are limited to short-term aspects of clinical and functional remission. CONCLUSIONS: Early improvement in joy during the first 2 weeks of treatment is strongly specific for treatment response and remission. The frequency of joy captures the predictivity and may deserve further study regarding inclusion in depressive rating scales. PMID- 26160154 TI - Prefrontal gyrification in psychotic bipolar I disorder vs. schizophrenia. AB - Bipolar disorder and schizophrenia share phenotypic and genotypic features, but might differ in aspects of abnormal neurodevelopmental trajectories. We studied gyrification, a marker of early developmental pathology, in high-resolution MRI scans of 34 patients with schizophrenia, 17 euthymic bipolar I disorder patients with previous psychotic symptoms, and 34 matched healthy controls in order to test the hypothesis of overlapping and diverging prefrontal gyrification abnormalities. We applied a novel, validated method for measuring local gyrification in each vertex point of the reconstructed cortical surface. Psychotic bipolar I patients had higher gyrification in dorsal anterior and infragenual cingulate cortex compared to either schizophrenia or healthy controls, while schizophrenia patients had higher gyrification than controls in anterior medial (BA 10) and orbitofrontal areas, altogether indicating disease specific alterations in the prefrontal cortex. Our findings indicate gyrification changes in a specific subgroup of bipolar I disorder to affect an area relevant to emotion regulation, and distinct from changes seen in schizophrenia. PMID- 26160155 TI - Characterization of kappa opioid receptor mediated, dynorphin-stimulated [35S]GTPgammaS binding in mouse striatum for the evaluation of selective KOR ligands in an endogenous setting. AB - Differential modulation of kappa opioid receptor (KOR) signaling has been a proposed strategy for developing therapies for drug addiction and depression by either activating or blocking this receptor. Hence, there have been significant efforts to generate ligands with diverse pharmacological properties including partial agonists, antagonists, allosteric modulators as well as ligands that selectively activate some pathways while not engaging others (biased agonists). It is becoming increasingly evident that G protein coupled receptor signaling events are context dependent and that what may occur in cell based assays may not be fully indicative of signaling events that occur in the naturally occurring environment. As new ligands are developed, it is important to assess their signaling capacity in relevant endogenous systems in comparison to the performance of endogenous agonists. Since KOR is considered the cognate receptor for dynorphin peptides we have evaluated the selectivity profiles of dynorphin peptides in wild-type (WT), KOR knockout (KOR-KO), and mu opioid receptor knockout (MOR-KO) mice using [35S]GTPgammaS binding assay in striatal membrane preparations. We find that while the small molecule KOR agonist U69,593, is very selective for KOR, dynorphin peptides promiscuously stimulate G protein signaling in striatum. Furthermore, our studies demonstrate that norBNI and 5'GNTI are highly nonselective antagonists as they maintain full potency and efficacy against dynorphin signaling in the absence of KOR. Characterization of a new KOR antagonist, which may be more selective than NorBNI and 5'GNTI, is presented using this approach. PMID- 26160156 TI - SURPRISING RESULTS: HIV TESTING AND CHANGES IN CONTRACEPTIVE PRACTICES AMONG YOUNG WOMEN IN MALAWI. AB - This study uses eight waves of data from the population-based Tsogolo la Thanzi study (2009-2011) in rural Malawi to examine changes in young women's contraceptive practices, including the use of condoms, non-barrier contraceptive methods and abstinence, following positive and negative HIV tests. The analysis factors in women's prior perceptions of their HIV status that may already be shaping their behaviour and separates surprise HIV test results from those that merely confirm what was already believed. Fixed-effects logistic regression models show that HIV testing frequently affects the contraceptive practices of young Malawian women, particularly when the test yields an unexpected result. Specifically, women who are surprised to test HIV positive increase their condom use and are more likely to use condoms consistently. Following an HIV-negative test (whether a surprise or expected), women increase their use of condoms and decrease their use of non-barrier contraceptives; the latter may be due to an increase in abstinence following a surprise negative result. Changes in condom use following HIV testing are robust to the inclusion of potential explanatory mechanisms, including fertility preferences, relationship status and the perception that a partner is HIV positive. The results demonstrate that both positive and negative tests can influence women's sexual and reproductive behaviours, and emphasize the importance of conceptualizing of HIV testing as offering new information only insofar as results deviate from prior perceptions of HIV status. PMID- 26160157 TI - Six new prenylated acetophenone derivatives from the leaves of Acronychia oligophlebia. AB - Six new prenylated acetophenone derivatives were isolated from the leaves of Acronychia oligophlebia. The chemical structures of them were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The cytotoxic activity of the isolates was evaluated against MCF-7 cells. Among these compounds, 2 and 6 exhibited mild cytotoxic activity with IC50 values of 33.5 and 25.6 MUM, respectively. PMID- 26160158 TI - The Interaction Between MiR-141 and lncRNA-H19 in Regulating Cell Proliferation and Migration in Gastric Cancer. AB - BACKGROUND/AIMS: Non-coding RNAs including miRNA and lncRNA had been reported to regulate gene expression and were both related to cancer progression. MicroRNA 141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and H19 has also been demonstrated to promote malignancy in various cancers. We aimed to determine the correlation between miR-141 and H19 and their roles in gastric cancer in this study. METHODS: H19 and miR-141 expression were detected by qRT-PCR. By bioinformatic analysis and luciferase assay we examined the correlation between H19 and miR-141 in vitro. RESULTS: H19 expression was found to be inversely correlated to miR-141 expression in gastric cancer cells and tissues. H19 promotes malignancy including proliferation and invasion whereas miR-141 suppresses malignancy in human cancer cells. MiR-141 binds to H19 in a sequence specific manner, and suppresses H19 expression and functions including proliferation and invasion. MiR-141 could also regulate H19 target genes and miR-141 inhibitor restores H19 siRNA function, while H19 regulates miR-141 target gene ZEB1. CONCLUSION: These results were the first to demonstrate that H19 and miR-141 could compete with each other and affect their target genes in gastric cancer, which provide important clues for understanding the key roles of lncRNA-miRNA functional network in cancer. PMID- 26160159 TI - How would you persuade reluctant commissioners to purchase maxillofacial services from your Trust? PMID- 26160160 TI - Resorptive remodeling in maxillary anterior region after bimaxillary surgery for skeletal Class III deformities. AB - The aim of this retrospective study was to evaluate bony remodelling in the anterior region of the maxilla after bimaxillary surgery for skeletal Class III deformities preoperatively, immediately postoperatively, and 6 months postoperatively. For accurate analysis, cone-beam computed tomographic (CT) images of 29 patients (12 men and 17 women; mean age 22 (range 19 to 44) years) were used. The nasopalatine canal, unaffected by the maxillary Le Fort I osteotomy, was used for the reference points (posterosuperior, midpoint, and posteroinferior). The changes in the distance from each of the points on the nasopalatine canal to the corresponding anterior border of the maxilla were measured and analysed at the 3 stages (p<0.05). Bony resorption was apparent during the postoperative period, and the mean resorption was -1.13 (1.53) mm at the posterosuperior level, -0.92 (0.83) mm at the midpoint, and -0.83 (0.88) mm at the posteroinferior level (p<0.01). These findings show that there had been resorptive remodelling postoperatively in the anterior maxillary region after bimaxillary surgery with superior maxillary movement, which suggests that the postoperative change in the position of point A is affected by operative movement as well as by postoperative relapse and bony remodelling. PMID- 26160161 TI - New device for palatal expansion in conjunction with the Le Fort I osteotomy. PMID- 26160162 TI - Cost of Screening, Brief Intervention, and Referral to Treatment in Health Care Settings. AB - AIMS: This study analyzed service unit and annual costs of substance abuse screening, brief intervention, and referral to treatment (SBIRT) programs implemented in emergency department (ED), inpatient, and outpatient medical settings in three U.S. states and one tribal organization. METHODS: Unit costs and annual costs were estimated from the perspective of service providers. Data for unit costs came from 26 performance sites, and data for annual costs came from 10 programs. A bottom-up approach was used to derive unit costs and included labor, space, and materials used in each SBIRT activity. Activities included direct SBIRT services and activities that support direct service delivery. Labor time spent in each activity was collected by trained observers using a time-and motion approach. A top-down approach used cost questionnaires completed by program administrators to calculate annual costs and included labor, space, contracted services, overhead, training, travel, equipment, and supplies and materials. Costs were estimated in 2012 U.S. dollars. RESULTS: Average unit costs for prescreening, screening, brief intervention, brief treatment, and referral to treatment were $0.61, $6.59, $10.48, $22.63, and $12.06 in ED; $0.86, $6.33, $9.07, $27.61, and $8.03 in inpatient; and $0.84, $3.98, $7.81, $27.94, and $9.23 in outpatient settings, respectively; over half of the costs were attributable to support activities. Across all settings, the average cost to provide SBIRT per positive screen, for 1year, was about $400. CONCLUSIONS: Support activities comprise a large proportion of costs. Health administrators can use the results to budget and compare how much sites are reimbursed for SBIRT to how much services actually cost. PMID- 26160163 TI - SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells. AB - SETDB1, a histone methyltransferase responsible for methylation of histone H3 lysine 9 (H3K9), is involved in maintenance of embryonic stem (ES) cells and early embryonic development of the mouse. However, how SETDB1 regulates gene expression during development is largely unknown. Here, we characterized genome wide SETDB1 binding and H3K9 trimethylation (H3K9me3) profiles in mouse ES cells and uncovered two distinct classes of SETDB1 binding sites, termed solo and ensemble peaks. The solo peaks were devoid of H3K9me3 and enriched near developmental regulators while the ensemble peaks were associated with H3K9me3. A subset of the SETDB1 solo peaks, particularly those near neural development related genes, was found to be associated with Polycomb Repressive Complex 2 (PRC2) as well as PRC2-interacting proteins JARID2 and MTF2. Genetic deletion of Setdb1 reduced EZH2 binding as well as histone 3 lysine 27 (H3K27) trimethylation level at SETDB1 solo peaks and facilitated neural differentiation. Furthermore, we found that H3K27me3 inhibits SETDB1 methyltransferase activity. The currently identified reciprocal action between SETDB1 and PRC2 reveals a novel mechanism underlying ES cell pluripotency and differentiation regulation. PMID- 26160164 TI - A widespread role of the motif environment in transcription factor binding across diverse protein families. AB - Transcriptional regulation requires the binding of transcription factors (TFs) to short sequence-specific DNA motifs, usually located at the gene regulatory regions. Interestingly, based on a vast amount of data accumulated from genomic assays, it has been shown that only a small fraction of all potential binding sites containing the consensus motif of a given TF actually bind the protein. Recent in vitro binding assays, which exclude the effects of the cellular environment, also demonstrate selective TF binding. An intriguing conjecture is that the surroundings of cognate binding sites have unique characteristics that distinguish them from other sequences containing a similar motif that are not bound by the TF. To test this hypothesis, we conducted a comprehensive analysis of the sequence and DNA shape features surrounding the core-binding sites of 239 and 56 TFs extracted from in vitro HT-SELEX binding assays and in vivo ChIP-seq data, respectively. Comparing the nucleotide content of the regions around the TF bound sites to the counterpart unbound regions containing the same consensus motifs revealed significant differences that extend far beyond the core-binding site. Specifically, the environment of the bound motifs demonstrated unique sequence compositions, DNA shape features, and overall high similarity to the core-binding motif. Notably, the regions around the binding sites of TFs that belong to the same TF families exhibited similar features, with high agreement between the in vitro and in vivo data sets. We propose that these unique features assist in guiding TFs to their cognate binding sites. PMID- 26160165 TI - Genome specialization and decay of the strangles pathogen, Streptococcus equi, is driven by persistent infection. AB - Strangles, the most frequently diagnosed infectious disease of horses worldwide, is caused by Streptococcus equi. Despite its prevalence, the global diversity and mechanisms underlying the evolution of S. equi as a host-restricted pathogen remain poorly understood. Here, we define the global population structure of this important pathogen and reveal a population replacement in the late 19th or early 20th Century. Our data reveal a dynamic genome that continues to mutate and decay, but also to amplify and acquire genes despite the organism having lost its natural competence and become host-restricted. The lifestyle of S. equi within the horse is defined by short-term acute disease, strangles, followed by long term infection. Population analysis reveals evidence of convergent evolution in isolates from post-acute disease samples as a result of niche adaptation to persistent infection within a host. Mutations that lead to metabolic streamlining and the loss of virulence determinants are more frequently found in persistent isolates, suggesting that the pathogenic potential of S. equi reduces as a consequence of long-term residency within the horse post-acute disease. An example of this is the deletion of the equibactin siderophore locus that is associated with iron acquisition, which occurs exclusively in persistent isolates, and renders S. equi significantly less able to cause acute disease in the natural host. We identify several loci that may similarly be required for the full virulence of S. equi, directing future research toward the development of new vaccines against this host-restricted pathogen. PMID- 26160166 TI - Tipping the balance between good and evil: aberrant 14-3-3zeta expression drives oncogenic TGF-beta signaling in metastatic breast cancers. AB - Transforming growth factor beta (TGF-beta) readily suppresses the development of early-stage breast cancers, an activity that gives way to tumor promotion in their late-stage counterparts. The molecular mechanisms underlying this mysterious switch in TGF-beta function remain murky. In addressing this conundrum, Xu et al. observed aberrant 14-3-3zeta expression to prevent the formation of tumor-suppressive Smad2/3:p53 complexes, while simultaneously driving the generation of oncogenic Smad2/3:Gli2 complexes. Once formed, Smad2/3:Gli2 complexes stimulate the expression of parathyroid hormone-related protein necessary for breast cancer metastasis to bone. This viewpoint highlights 14-3-3zeta as an essential driver of oncogenic signaling by Smad2/3 and TGF-beta in metastatic breast cancers. PMID- 26160168 TI - [Use of neuromuscular blockers in Brazil]. AB - The objective of this study was to evaluate how Brazilian anesthesiologists are using neuromuscular blockers (NMB), focusing on how they establish the diagnosis of postoperative residual curarization and the incidence of complications associated with the use of NMB. A questionnaire was sent to anesthesiologists inviting them to participate in the study. The online data collection remained open from March 2012 to June 2013. During the study period, 1296 responses were collected. Rocuronium, atracurium, and cisatracurium were the main neuromuscular blockers used in cases of elective surgery. Succinylcholine and rocuronium were the main NMB used in cases of emergency surgery. Less than 15% of anesthesiologists reported the frequent use of neuromuscular function monitors. Only 18% of those involved in the study reported that all workplaces have such a monitor. Most respondents reported using only the clinical criteria to assess whether the patient is recovered from the muscle relaxant. Most respondents also reported always using some form of neuromuscular blockade reversal. The major complications attributed to NMB were residual curarization and prolonged blockade. Eighteen anesthesiologists reported death attributed to NMB. Residual or prolonged blockade is possibly recorded as a result of the high rate of using clinical criteria to diagnose whether the patient has recovered or not from motor block and, as a corollary, the poor use of neuromuscular transmission monitors in daily practice. PMID- 26160167 TI - Helicobacter pylori virulence factor CagA promotes tumorigenesis of gastric cancer via multiple signaling pathways. AB - Helicobacter pylori (H. pylori) infection is strongly associated with the development of gastric diseases but also with several extragastric diseases. The clinical outcomes caused by H. pylori infection are considered to be associated with a complex combination of host susceptibility, environmental factors and bacterial isolates. Infections involving H. pylori strains that possess the virulence factor CagA have a worse clinical outcome than those involving CagA negative strains. It is remarkable that CagA-positive H. pylori increase the risk for gastric cancer over the risk associated with H. pylori infection alone. CagA behaves as a bacterial oncoprotein playing a key role in H. pylori-induced gastric cancer. Activation of oncogenic signaling pathways and inactivation of tumor suppressor pathways are two crucial events in the development of gastric cancer. CagA shows the ability to affect the expression or function of vital protein in oncogenic or tumor suppressor signaling pathways via several molecular mechanisms, such as direct binding or interaction, phosphorylation of vital signaling proteins and methylation of tumor suppressor genes. As a result, CagA continuously dysregulates of these signaling pathways and promotes tumorigenesis. Recent research has enriched our understanding of how CagA effects on these signaling pathways. This review summarizes the results of the most relevant studies, discusses the complex molecular mechanism involved and attempts to delineate the entire signaling pathway. PMID- 26160169 TI - Activation of Human Toll-like Receptor 4 (TLR4).Myeloid Differentiation Factor 2 (MD-2) by Hypoacylated Lipopolysaccharide from a Clinical Isolate of Burkholderia cenocepacia. AB - Lung infection by Burkholderia species, in particular Burkholderia cenocepacia, accelerates tissue damage and increases post-lung transplant mortality in cystic fibrosis patients. Host-microbe interplay largely depends on interactions between pathogen-specific molecules and innate immune receptors such as Toll-like receptor 4 (TLR4), which recognizes the lipid A moiety of the bacterial lipopolysaccharide (LPS). The human TLR4.myeloid differentiation factor 2 (MD-2) LPS receptor complex is strongly activated by hexa-acylated lipid A and poorly activated by underacylated lipid A. Here, we report that B. cenocepacia LPS strongly activates human TLR4.MD-2 despite its lipid A having only five acyl chains. Furthermore, we show that aminoarabinose residues in lipid A contribute to TLR4-lipid A interactions, and experiments in a mouse model of LPS-induced endotoxic shock confirmed the proinflammatory potential of B. cenocepacia penta acylated lipid A. Molecular modeling combined with mutagenesis of TLR4-MD-2 interactive surfaces suggests that longer acyl chains and the aminoarabinose residues in the B. cenocepacia lipid A allow exposure of the fifth acyl chain on the surface of MD-2 enabling interactions with TLR4 and its dimerization. Our results provide a molecular model for activation of the human TLR4.MD-2 complex by penta-acylated lipid A explaining the ability of hypoacylated B. cenocepacia LPS to promote proinflammatory responses associated with the severe pathogenicity of this opportunistic bacterium. PMID- 26160170 TI - Functional Analyses of Resurrected and Contemporary Enzymes Illuminate an Evolutionary Path for the Emergence of Exolysis in Polysaccharide Lyase Family 2. AB - Family 2 polysaccharide lyases (PL2s) preferentially catalyze the beta elimination of homogalacturonan using transition metals as catalytic cofactors. PL2 is divided into two subfamilies that have been generally associated with secretion, Mg(2+) dependence, and endolysis (subfamily 1) and with intracellular localization, Mn(2+) dependence, and exolysis (subfamily 2). When present within a genome, PL2 genes are typically found as tandem copies, which suggests that they provide complementary activities at different stages along a catabolic cascade. This relationship most likely evolved by gene duplication and functional divergence (i.e. neofunctionalization). Although the molecular basis of subfamily 1 endolytic activity is understood, the adaptations within the active site of subfamily 2 enzymes that contribute to exolysis have not been determined. In order to investigate this relationship, we have conducted a comparative enzymatic analysis of enzymes dispersed within the PL2 phylogenetic tree and elucidated the structure of VvPL2 from Vibrio vulnificus YJ016, which represents a transitional member between subfamiles 1 and 2. In addition, we have used ancestral sequence reconstruction to functionally investigate the segregated evolutionary history of PL2 progenitor enzymes and illuminate the molecular evolution of exolysis. This study highlights that ancestral sequence reconstruction in combination with the comparative analysis of contemporary and resurrected enzymes holds promise for elucidating the origins and activities of other carbohydrate active enzyme families and the biological significance of cryptic metabolic pathways, such as pectinolysis within the zoonotic marine pathogen V. vulnificus. PMID- 26160171 TI - Mucin-like Region of Herpes Simplex Virus Type 1 Attachment Protein Glycoprotein C (gC) Modulates the Virus-Glycosaminoglycan Interaction. AB - Glycoprotein C (gC) mediates the attachment of HSV-1 to susceptible host cells by interacting with glycosaminoglycans (GAGs) on the cell surface. gC contains a mucin-like region located near the GAG-binding site, which may affect the binding activity. Here, we address this issue by studying a HSV-1 mutant lacking the mucin-like domain in gC and the corresponding purified mutant protein (gCDeltamuc) in cell culture and GAG-binding assays, respectively. The mutant virus exhibited two functional alterations as compared with native HSV-1 (i.e. decreased sensitivity to GAG-based inhibitors of virus attachment to cells and reduced release of viral particles from the surface of infected cells). Kinetic and equilibrium binding characteristics of purified gC were assessed using surface plasmon resonance-based sensing together with a surface platform consisting of end-on immobilized GAGs. Both native gC and gCDeltamuc bound via the expected binding region to chondroitin sulfate and sulfated hyaluronan but not to the non-sulfated hyaluronan, confirming binding specificity. In contrast to native gC, gCDeltamuc exhibited a decreased affinity for GAGs and a slower dissociation, indicating that once formed, the gCDeltamuc-GAG complex is more stable. It was also found that a larger number of gCDeltamuc bound to a single GAG chain, compared with native gC. Taken together, our data suggest that the mucin-like region of HSV-1 gC is involved in the modulation of the GAG-binding activity, a feature of importance both for unrestricted virus entry into the cells and release of newly produced viral particles from infected cells. PMID- 26160172 TI - Mac-1 Regulates IL-13 Activity in Macrophages by Directly Interacting with IL 13Ralpha1. AB - Mac-1 exhibits a unique inhibitory activity toward IL-13-induced JAK/STAT activation and thereby regulates macrophage to foam cell transformation. However, the underlying molecular mechanism is unknown. In this study, we report the identification of IL-13Ralpha1, a component of the IL-13 receptor (IL-13R), as a novel ligand of integrin Mac-1, using a co-evolution-based algorithm. Biochemical analyses demonstrated that recombinant IL-13Ralpha1 binds Mac-1 in a purified system and supports Mac-1-mediated cell adhesion. Co-immunoprecipitation experiments revealed that endogenous Mac-1 forms a complex with IL-13Ralpha1 in solution, and confocal fluorescence microscopy demonstrated that these two receptors co-localize with each other on the surface of macrophages. Moreover, we found that genetic inactivation of Mac-1 promotes IL-13-induced JAK/STAT activation in macrophages, resulting in enhanced polarization along the alternative activation pathway. Importantly, we observed that Mac-1(-/-) macrophages exhibit increased expression of foam cell differentiation markers including 15-lipoxygenase and lectin-type oxidized LDL receptor-1 both in vitro and in vivo. Indeed, we found that Mac-1(-/-)LDLR(-/-) mice develop significantly more foam cells than control LDLR(-/-) mice, using an in vivo model of foam cell formation. Together, our data establish for the first time a molecular mechanism by which Mac-1 regulates the signaling activity of IL-13 in macrophages. This newly identified IL-13Ralpha1/Mac-1-dependent pathway may offer novel targets for therapeutic intervention in the future. PMID- 26160173 TI - Aerobic Growth of Escherichia coli Is Reduced, and ATP Synthesis Is Selectively Inhibited when Five C-terminal Residues Are Deleted from the epsilon Subunit of ATP Synthase. AB - F-type ATP synthases are rotary nanomotor enzymes involved in cellular energy metabolism in eukaryotes and eubacteria. The ATP synthase from Gram-positive and negative model bacteria can be autoinhibited by the C-terminal domain of its epsilon subunit (epsilonCTD), but the importance of epsilon inhibition in vivo is unclear. Functional rotation is thought to be blocked by insertion of the latter half of the epsilonCTD into the central cavity of the catalytic complex (F1). In the inhibited state of the Escherichia coli enzyme, the final segment of epsilonCTD is deeply buried but has few specific interactions with other subunits. This region of the epsilonCTD is variable or absent in other bacteria that exhibit strong epsilon-inhibition in vitro. Here, genetically deleting the last five residues of the epsilonCTD (epsilonDelta5) caused a greater defect in respiratory growth than did the complete absence of the epsilonCTD. Isolated membranes with epsilonDelta5 generated proton-motive force by respiration as effectively as with wild-type epsilon but showed a nearly 3-fold decrease in ATP synthesis rate. In contrast, the epsilonDelta5 truncation did not change the intrinsic rate of ATP hydrolysis with membranes. Further, the epsilonDelta5 subunit retained high affinity for isolated F1 but reduced the maximal inhibition of F1-ATPase by epsilon from >90% to ~20%. The results suggest that the epsilonCTD has distinct regulatory interactions with F1 when rotary catalysis operates in opposite directions for the hydrolysis or synthesis of ATP. PMID- 26160174 TI - The Role of the Pleckstrin Homology Domain-containing Protein CKIP-1 in Activation of p21-activated Kinase 1 (PAK1). AB - Upon growth factor stimulation, PAK1 is recruited to the plasma membrane and activated by a mechanism that requires its phosphorylation at Ser-223 by the protein kinase CK2. However, the upstream signaling molecules that regulate this phosphorylation event are not clearly defined. Here, we demonstrate a major role of the CK2alpha-interacting protein CKIP-1 in activation of PAK1. CK2alpha, CKIP 1, and PAK1 are translocated to membrane ruffles in response to the epidermal growth factor (EGF), where CKIP-1 mediates the interaction between CK2alpha and PAK1 in a PI3K-dependent manner. Consistently, PAK1 mediates phosphorylation and modulation of the activity of p41-Arc, one of its plasma membrane substrate, in a fashion that requires PI3K and CKIP-1. Moreover, CKIP-1 knockdown or PI3K inhibition suppresses PAK1-mediated cell migration and invasion, demonstrating the physiological significance of the PI3K-CKIP-1-CK2-PAK1 signaling pathway. Taken together, these findings identify a novel mechanism for the activation of PAK1 at the plasma membrane, which is critical for cell migration and invasion. PMID- 26160175 TI - Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease. AB - Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 A resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease. PMID- 26160176 TI - Rate-determining Step of Flap Endonuclease 1 (FEN1) Reflects a Kinetic Bias against Long Flaps and Trinucleotide Repeat Sequences. AB - Flap endonuclease 1 (FEN1) is a structure-specific nuclease responsible for removing 5'-flaps formed during Okazaki fragment maturation and long patch base excision repair. In this work, we use rapid quench flow techniques to examine the rates of 5'-flap removal on DNA substrates of varying length and sequence. Of particular interest are flaps containing trinucleotide repeats (TNR), which have been proposed to affect FEN1 activity and cause genetic instability. We report that FEN1 processes substrates containing flaps of 30 nucleotides or fewer at comparable single-turnover rates. However, for flaps longer than 30 nucleotides, FEN1 kinetically discriminates substrates based on flap length and flap sequence. In particular, FEN1 removes flaps containing TNR sequences at a rate slower than mixed sequence flaps of the same length. Furthermore, multiple-turnover kinetic analysis reveals that the rate-determining step of FEN1 switches as a function of flap length from product release to chemistry (or a step prior to chemistry). These results provide a kinetic perspective on the role of FEN1 in DNA replication and repair and contribute to our understanding of FEN1 in mediating genetic instability of TNR sequences. PMID- 26160177 TI - The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells. AB - Re-activation of androgen receptor (AR) activity is the main driver for development of castration-resistant prostate cancer. We previously reported that the ubiquitin ligase Siah2 enhanced AR transcriptional activity and prostate cancer cell growth. Among the genes we found to be regulated by Siah2 was AKR1C3, which encodes a key androgen biosynthetic enzyme implicated in castration resistant prostate cancer development. Here, we found that Siah2 inhibition in CWR22Rv1 prostate cancer cells decreased AKR1C3 expression as well as intracellular androgen levels, concomitant with inhibition of cell growth in vitro and in orthotopic prostate tumors. Re-expression of either wild-type or catalytically inactive forms of AKR1C3 partially rescued AR activity and growth defects in Siah2 knockdown cells, suggesting a nonenzymatic role for AKR1C3 in these outcomes. Unexpectedly, AKR1C3 re-expression in Siah2 knockdown cells elevated Siah2 protein levels, whereas AKR1C3 knockdown had the opposite effect. We further found that AKR1C3 can bind Siah2 and inhibit its self-ubiquitination and degradation, thereby increasing Siah2 protein levels. We observed parallel expression of Siah2 and AKR1C3 in human prostate cancer tissues. Collectively, our findings identify a new role for AKR1C3 in regulating Siah2 stability and thus enhancing Siah2-dependent regulation of AR activity in prostate cancer cells. PMID- 26160178 TI - Dimerization Mediated by a Divergent Forkhead-associated Domain Is Essential for the DNA Damage and Spindle Functions of Fission Yeast Mdb1. AB - MDC1 is a key factor of DNA damage response in mammalian cells. It possesses two phospho-binding domains. In its C terminus, a tandem BRCA1 C-terminal domain binds phosphorylated histone H2AX, and in its N terminus, a forkhead-associated (FHA) domain mediates a phosphorylation-enhanced homodimerization. The FHA domain of the Drosophila homolog of MDC1, MU2, also forms a homodimer but utilizes a different dimer interface. The functional importance of the dimerization of MDC1 family proteins is uncertain. In the fission yeast Schizosaccharomyces pombe, a protein sharing homology with MDC1 in the tandem BRCA1 C-terminal domain, Mdb1, regulates DNA damage response and mitotic spindle functions. Here, we report the crystal structure of the N-terminal 91 amino acids of Mdb1. Despite a lack of obvious sequence conservation to the FHA domain of MDC1, this region of Mdb1 adopts an FHA-like fold and is therefore termed Mdb1-FHA. Unlike canonical FHA domains, Mdb1-FHA lacks all the conserved phospho-binding residues. It forms a stable homodimer through an interface distinct from those of MDC1 and MU2. Mdb1 FHA is important for the localization of Mdb1 to DNA damage sites and the spindle midzone, contributes to the roles of Mdb1 in cellular responses to genotoxins and an antimicrotubule drug, and promotes in vitro binding of Mdb1 to a phospho-H2A peptide. The defects caused by the loss of Mdb1-FHA can be rescued by fusion with either of two heterologous dimerization domains, suggesting that the main function of Mdb1-FHA is mediating dimerization. Our data support that FHA mediated dimerization is conserved for MDC1 family proteins. PMID- 26160179 TI - Pre-steady-state Kinetic Analysis of a Family D DNA Polymerase from Thermococcus sp. 9 degrees N Reveals Mechanisms for Archaeal Genomic Replication and Maintenance. AB - Family D DNA polymerases (polDs) have been implicated as the major replicative polymerase in archaea, excluding the Crenarchaeota branch, and bear little sequence homology to other DNA polymerase families. Here we report a detailed kinetic analysis of nucleotide incorporation and exonuclease activity for a Family D DNA polymerase from Thermococcus sp. 9 degrees N. Pre-steady-state single-turnover nucleotide incorporation assays were performed to obtain the kinetic parameters, kpol and Kd, for correct nucleotide incorporation, incorrect nucleotide incorporation, and ribonucleotide incorporation by exonuclease deficient polD. Correct nucleotide incorporation kinetics revealed a relatively slow maximal rate of polymerization (kpol ~ 2.5 s(-1)) and especially tight nucleotide binding (Kd (dNTP) ~ 1.7 MUm), compared with DNA polymerases from Families A, B, C, X, and Y. Furthermore, pre-steady-state nucleotide incorporation assays revealed that polD prevents the incorporation of incorrect nucleotides and ribonucleotides primarily through reduced nucleotide binding affinity. Pre-steady-state single-turnover assays on wild-type 9 degrees N polD were used to examine 3'-5' exonuclease hydrolysis activity in the presence of Mg(2+) and Mn(2+). Interestingly, substituting Mn(2+) for Mg(2+) accelerated hydrolysis rates > 40-fold (kexo >= 110 s(-1) versus >= 2.5 s(-1)). Preference for Mn(2+) over Mg(2+) in exonuclease hydrolysis activity is a property unique to the polD family. The kinetic assays performed in this work provide critical insight into the mechanisms that polD employs to accurately and efficiently replicate the archaeal genome. Furthermore, despite the unique properties of polD, this work suggests that a conserved polymerase kinetic pathway is present in all known DNA polymerase families. PMID- 26160180 TI - Radiation-induced bystander effect in non-irradiated glioblastoma spheroid cells. AB - Radiation-induced bystander effects (RIBEs) are detected in cells that are not irradiated but receive signals from treated cells. The present study explored these bystander effects in a U87MG multicellular tumour spheroid model. A medium transfer technique was employed to induce the bystander effect, and colony formation assay was used to evaluate the effect. Relative changes in expression of BAX, BCL2, JNK and ERK genes were analysed using RT-PCR to investigate the RIBE mechanism. A significant decrease in plating efficiency was observed for both bystander and irradiated cells. The survival fraction was calculated for bystander cells to be 69.48% and for irradiated cells to be 34.68%. There was no change in pro-apoptotic BAX relative expression, but anti-apoptotic BCL2 showed downregulation in both irradiated and bystander cells. Pro-apoptotic JNK in bystander samples and ERK in irradiated samples were upregulated. The clonogenic survival data suggests that there was a classic RIBE in U87MG spheroids exposed to 4 Gy of X-rays, using a medium transfer technique. Changes in the expression of pro- and anti-apoptotic genes indicate involvement of both intrinsic apoptotic and MAPK pathways in inducing these effects. PMID- 26160181 TI - Initial experience of radiotherapy plus cetuximab for Japanese head and neck cancer patients. AB - In Japan, cetuximab with concurrent bioradiotherapy (BRT) for squamous cell carcinoma of head and neck (SCCHN) was approved in December 2012. We herein report our initial experience of BRT, with special emphasis on acute toxicities of this combination therapy. Thirty-one non-metastatic SCCHN patients who underwent BRT using cetuximab between July 2013 and June 2014 were retrospectively evaluated. All patients received cetuximab with a loading dose of 400 mg/m(2) one week before the start of radiotherapy, followed by 250 mg/m(2) per week during radiotherapy. The median cycle of cetuximab was seven cycles and the median dose of radiotherapy was 70 Gy. Twenty-five patients (80.6%) accomplished planned radiotherapy and six cycles or more cetuximab administration. Six patients (19.4%) discontinued cetuximab. Grade 3 dermatitis, mucositis and infusion reaction occurred in 19.4%, 48.3% and 3.2%, respectively. One patient experienced Grade 3 gastrointestinal bleeding caused by diverticular hemorrhage during BRT. Grade 3 drug-induced pneumonitis occurred in two patients. The response rate was 74%, including 55% with a complete response. BRT using cetuximab for Japanese patients with SCCHN was feasible as an alternative for cisplatin-based concurrent chemoradiation, although longer follow-up is necessary to evaluate late toxicities. PMID- 26160182 TI - A new story ARC for alpha-granule formation. PMID- 26160183 TI - To be or not to be HIV+, that is no longer the question. PMID- 26160184 TI - PD-L1 blockade: rejuvenating T cells in CLL. PMID- 26160185 TI - Splicing up the classification of myelodysplasia. PMID- 26160186 TI - Selectin' for NETs. PMID- 26160187 TI - Iron and erythropoietic porphyrias. PMID- 26160188 TI - Eculizumab treatment efficiently prevents C5 cleavage without C5a generation in vivo. PMID- 26160189 TI - Response: Maternal and cord C5a in response to eculizumab. PMID- 26160190 TI - Characterization of self-assembled virus-like particles of dromedary camel hepatitis e virus generated by recombinant baculoviruses. AB - Dromedary camel hepatitis E virus (DcHEV), a novel hepatitis E virus, has been identified in dromedary camels in Dubai, United Arab Emirates. The antigenicity, pathogenicity and epidemiology of this virus have been unclear. Here we first used a recombinant baculovirus expression system to express the 13 and 111 N terminus amino-acid-truncated DcHEV ORF2 protein in insect Tn5 cells, and we obtained two types of virus-like particles (VLPs) with densities of 1.300 g/cm(3) and 1.285 g/cm(3), respectively. The small VLPs (Dc4sVLPs) were estimated to be 24 nm in diameter, and were assembled by a protein with the molecular mass 53 kDa. The large VLPs (Dc3nVLPs and Dc4nVLPs) were 35 nm in diameter, and were assembled by a 64-kDa protein. An antigenic analysis demonstrated that DcHEV was cross-reactive with G1, G3-G6, ferret and rat HEVs, and DcHEV showed a stronger cross-reactivity to G1 G3-G6 HEV than it did to rat and ferret HEV. In addition, the antibody against DcHEV-LPs neutralized G1 and G3 HEV in a cell culture system, suggesting that the serotypes of these HEVs are identical. We also found that the amino acid residue Met-358 affects the small DcHEV-LPs assembly. PMID- 26160191 TI - Vitamin D deficiency and Alzheimer disease: Common links. AB - Vitamin D (VitD) deficiency is a worldwide epidemic with estimates of 1 billion affected. In addition to the classically known roles of VitD in calcium regulation and bone health, recent studies demonstrated VitD to be an essential/vital neurosteroid hormone playing a wide variety of essential protective and regulatory roles in the brain. This paper reviews much of the mounting evidence of the detrimental effects of VitD deficiency on the brain and the association of many of these common links with Alzheimer's disease (AD). We also discuss the beneficial effects seen from VitD supplementation. Based on this accumulation of studies, we propose that VitD screening should be performed at least in those individuals at risk for VitD deficiency and AD. With appropriate medical counsel, those found to be VitD deficient should be considered for appropriate supplementation. PMID- 26160193 TI - Synthesis of conducting polymer nanospheres of high electrochemical activity. AB - We propose a novel approach to obtain conducting polymer nanoparticles with high electrochemical activity and a narrow size distribution. The method - templateless and seedless - uses polyacrylate microspheres to deliver the monomer for the polymerization reaction. Thus the obtained nanostructures have an active unblocked - surface allowing fast charge/ion-exchange and the formation of stable suspensions in water. The obtained nanostructures have the potential to be applied in different fields ranging from conductive coatings and additives for increasing electronic conductivity, to electrochemical sensors. PMID- 26160192 TI - A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix. AB - Appendiceal mucinous tumors (AMTs) are classified as low-grade appendiceal mucinous neoplasms (LAMNs) or mucinous adenocarcinomas (MACs), although their carcinogenesis is not well understood. As somatic activating mutations of GNAS are considered to be characteristic of LAMNs while TP53 mutations have been shown to be specific to MACs, MACs are unlikely to result from transformation of LAMNs. However, emerging evidence also shows the presence of GNAS mutations in MACs. We examined 16 AMTs (11 LAMNs and 5 MACs) for genetic alterations of GNAS, KRAS, BRAF, TP53, CTNNB1, and TERT promoter in order to elucidate the possibility of a shared genetic background in the two tumor types. Extensive histological examination revealed the presence of a low-grade component in all cases of MAC. GNAS mutations were detected in two LAMNs and in one MAC, although the GNAS mutation in this MAC was a nonsense mutation (Q227X) expected not to be activating mutation. TP53 mutations were detected in three LAMNs; they were frequently detected in MACs. KRAS mutations were detected in three LAMNs and three MACs, and CTNNB1 mutations were detected in two LAMNs. KRAS mutation and activating mutation of GNAS occurred exclusively in AMTs. BRAF and TERT mutations were not detected. Overexpression of p53 was observed in only two MACs, and p53 immunostaining clearly discriminated the high-grade lesion from a low-grade component in one. These findings suggest that p53 overexpression plays an important role in the carcinogenesis of AMTs and that, in addition to mutations of GNAS, KRAS and TP53 alterations might be shared by AMTs, thus providing evidence for the possible progression of LAMNs to MAC. PMID- 26160194 TI - Nanophotonic detection of freely interacting molecules on a single influenza virus. AB - Biomolecular interactions, such as antibody-antigen binding, are fundamental to many biological processes. At present, most techniques for analyzing these interactions require immobilizing one or both of the interacting molecules on an assay plate or a sensor surface. This is convenient experimentally but can constrain the natural binding affinity and capacity of the molecules, resulting in data that can deviate from the natural free-solution behavior. Here we demonstrate a label-free method for analyzing free-solution interactions between a single influenza virus and specific antibodies at the single particle level using near-field optical trapping and light-scattering techniques. We determine the number of specific antibodies binding to an optically trapped influenza virus by analyzing the change of the Brownian fluctuations of the virus. We develop an analytical model that determines the increased size of the virus resulting from antibodies binding to the virus membrane with uncertainty of +/- 1-2 nm. We present stoichiometric results of 26 +/- 4 (6.8 +/- 1.1 attogram) anti-influenza antibodies binding to an H1N1 influenza virus. Our technique can be applied to a wide range of molecular interactions because the nanophotonic tweezer can handle molecules from tens to thousands of nanometers in diameter. PMID- 26160195 TI - Resolving deep relationships of PACMAD grasses: a phylogenomic approach. AB - BACKGROUND: Plastome sequences for 18 species of the PACMAD grasses (subfamilies Panicoideae, Aristidoideae, Chloridoideae, Micrairoideae, Arundinoideae, Danthonioideae) were analyzed phylogenomically. Next generation sequencing methods were used to provide complete plastome sequences for 12 species. Sanger sequencing was performed to determine the plastome of one species, Hakonechloa macra, to provide a reference for annotation. These analyses were conducted to resolve deep subfamilial relationships within the clade. Divergence estimates were assessed to determine potential factors that led to the rapid radiation of this lineage and its dominance of warmer open habitats. RESULTS: New plastomes were completely sequenced and characterized for 13 PACMAD species. An autapomorphic ~1140 bp deletion was found in Hakonechloa macra putatively pseudogenizing rpl14 and eliminating rpl16 from this plastome. Phylogenomic analyses support Panicoideae as the sister group to the ACMAD clade. Complete plastome sequences provide greater support at deep nodes within the PACMAD clade. The initial diversification of PACMAD subfamilies was estimated to occur at 32.4 mya. CONCLUSIONS: Phylogenomic analyses of complete plastomes provides resolution for deep relationships of PACMAD grasses. The divergence estimate of 32.4 mya at the crown node of the PACMAD clade coincides with the Eocene-Oligocene Transition (EOT). The Eocene was a period of global cooling and drying, which led to forest fragmentation and the expansion of open habitats now dominated by these grasses. Understanding how these grasses are related and determining a cause for their rapid radiation allows for future predictions of grassland distribution in the face of a changing global climate. PMID- 26160196 TI - Cariprazine delays ouabain-evoked epileptiform spikes and loss of activity in rat hippocampal slices. AB - In the only bipolar cycling in vitro model, rat hippocampal slices are treated with the sodium pump inhibitor ouabain, which induces epileptiform activity, followed by refractory activity loss that recovers and cycles back to epileptiform activity. Thus, clinical cycling seen in patients with bipolar disorder is modeled on a cellular level as alternating hyperactivity and hypoactivity interspersed with normal activity. In this study, we tested the ability of cariprazine a new antipsychotic candidate to block ouabain-induced changes in rat hippocampal slices. Cycling of population spikes and epileptiform bursts was evoked using an extracellular stimulation electrode located in the Schaeffer collaterals of 400-um-thick rat hippocampal slices treated with ouabain (3.3MUM) alone or in combination with cariprazine (1, 5, 25, and 50uM). Responses were recorded using an extracellular electrode placed in the cell body layer of the CA1 region. Cariprazine 25 and 50uM delayed ouabain-induced epileptiform burst onset and subsequent activity loss. Lower cariprazine concentrations were ineffective. Cariprazine delays the onset of ouabain-induced epileptiform bursts and the loss of spiking activity similarly to that previously demonstrated with the mood stabilizer lithium. These results suggest that cariprazine may have therapeutic potential for treatment of bipolar disorder. PMID- 26160197 TI - Absence of bias in clinician ratings of everyday functioning among African American, Hispanic and Caucasian patients with schizophrenia. AB - A substantial research literature implicates potential racial/ethnic bias in the diagnosis of schizophrenia and in clinical ratings of psychosis. There is no similar information regarding bias effects on ratings of everyday functioning. Our aims were to determine if Caucasian raters vary in their ratings of the everyday functioning of schizophrenia patients of different ethnicities, to find out which factors determine accurate self-report of everyday functioning in different ethnic groups, and to know if depression has similar effects on the way people of different ethnicities self-report their current functionality. We analyzed data on 295 patients with schizophrenia who provided their self-report of their everyday functioning and also had a Caucasian clinician rating their functionality. Three racial/ethnic groups (African American (AA), Hispanic and Caucasian) were studied and analyzed on the basis of neurocognition, functional capacity, depression and real-world functional outcomes. No differences based on racial/ethnic status in clinician assessments of patients' functionality were found. Differences between racial groups were found in personal and maternal levels of education. Severity of depression was significantly correlated with accuracy of self-assessment of functioning in Caucasians, but not in AAs. Higher scores on neurocognition and functional capacity scales correlated with reduced overestimation of functioning in AAs, but not in Hispanics. This data might indicate that measurement of everyday functionality is less subject to rater bias than measurement of symptoms of schizophrenia. PMID- 26160198 TI - Temperament and psychopathological syndromes specific susceptibility for rubber hand illusion. AB - The aim of this study is to explore individual capacity for self-integration, susceptibility to the Rubber Hand Illusion (RHI) and the role of temperament factors in the emergence of body schema and body image dissociation. The RHI factors, proprioceptive drift, body ownership and body disownership were assessed in 48 university students. Personality and psychiatric vulnerability were measured by the Temperament and Character Inventory (TCI-R) and the Symptom Checklist-90-R (SCL-90-R). Our study pointed to the fact that the extent of behaviourally defined proprioceptive drift was associated with temperament factors, especially with Novelty Seeking and Harm Avoidance. Further, the ownership was associated with Symptom Checklist factors, especially with elevated Interpersonal Sensitivity and vulnerability to Schizotypy and Paranoid Ideation and elevated disownership score was found in the case of elevated Schizotypy, including a depersonalisation feeling when the RHI was induced. The RHI may be considered as a conflicting situation, in which a way to cope with incongruent multimodal, visual, haptic and proprioceptive stimulation provides an opportunity to test body integration and embodiment processes in healthy participants and patients without disadvantageous outcomes. The results support and replenish the two opposite processing models of the RHI with a third, temperament-based procedural mechanism. PMID- 26160199 TI - Do biometric parameters of the hand differentiate schizophrenia from other psychiatric disorders? A comparative evaluation using three mental health modules. AB - The link between schizophrenia and anomalies in the distal upper limb is well documented. Preliminary studies have identified a number of biometric parameters of the hand by which schizophrenics can be distinguished from matched controls. The current study seeks to determine whether patients with schizophrenia can be singled out from a disparate group of other mental disorders by using the same parameters. We studied three groups, totaling 134 men: 51 diagnosed with schizophrenia, 29 with anxiety and mood disorders, and 54 comprising a control group. Seven parameters were studied: the proximal interphalangeal joint, the eponychia of the middle and ring digits, two dermatoglyphic features, and two constitutional factors. Examiners evaluated the parameters based on photographs and prints. An initial Mann Whitney comparison showed no significant difference between the control group and those identified with anxiety and mood disorders. We therefore accounted for them as a single group. In a discriminant analysis, an overall accuracy of 78.4% was established with a sensitivity of 80.4% (schizophrenics identified correctly) and a specificity of 77.1% (controls identified correctly). These results suggest that the biometric parameters employed may be useful in identifying patients with schizophrenia from a disparate group of other mental disorders. PMID- 26160201 TI - Are conceptual abilities impaired in schizophrenia? AB - Whereas semantic processing deficits are well-documented in schizophrenia, conceptual abilities have been poorly explored. This study aims at specifically exploring conceptualization abilities in 34 adults fulfilling schizophrenia according to DSM-IV and 34 healthy controls with similar socio-demographic characteristics. The 2 groups were assessed on the WAIS-R similarities test and the concept generation test (Raoux et al., 2014) consisting of free-sorting 6 cards of pictures of animals and geometric shapes to be separated in two groups or categories based on common attributes. After each sorting, the participant is asked to explain his/her sorting. Whereas the schizophrenic patients performed significantly poorer than the control participants in the semantic knowledge and lexico-semantic tests, there was no difference neither in the WAIS-R similarities test nor in the concept generation test, which supports the hypothesis of preserved high level conceptualization abilities in schizophrenia. However, qualitative differences in performing the concept generation test were evidenced. The patients used more often mixed criteria leading them to compare two different hierarchical levels (e.g., low-level physical attributes vs. high-level semantic criteria). Furthermore, the qualitative analysis based on the explanations provided by the participants shows that the categorizations achieved by schizophrenic patients are more often based on unexpected criteria. PMID- 26160200 TI - Genes involved in pruning and inflammation are enriched in a large mega-sample of patients affected by Schizophrenia and Bipolar Disorder and controls. AB - A molecular pathway analysis has been performed in order to complement previous genetic investigations on Schizophrenia. 4486 Schizophrenic patients and 4477 controls served as the investigation sample. 3521 Bipolar patients and 3195 controls served as replication sample. A molecular pathway associated with the neuronal pruning activity was found to be enriched in subjects with Schizophrenia compared to controls. HLA-C and HLA-DRA had more SNPs associated with both Schizophrenia and Bipolar Disorder than expected by chance. PMID- 26160202 TI - Relationships between coronary angiography, mood, anxiety and insomnia. AB - The purpose of this study was to investigate and compare the anxiety, depression and insomnia levels in the pre- and post-coronary angiography in patients undergoing elective coronary angiography due to suspected coronary artery disease. This prospective cross-sectional study consisted of 120 patients consecutively underwent coronary angiogram (CAG) between January and August 2014 in Departments of Cardiology. The mean age was 57.49 (SD+/-9.73), and 58.3% of the sample were women. The Hospital Anxiety and Depression Scale, Profile of Mood States Scale, Spielberger's State-Trait Anxiety Inventory, and Insomnia Severity Index were used. Patients were subsumed under 2 groups as normal and critical according to the presence or the absence of visually severe stenosis in at least one coronary artery. Subjects with significant stenosis had greater mean scores on depression-dejection and anger-hostility sub-scales of the POMS in the post angiography than pre-angiography scores. We found that older age and having a physical illness significantly contributed to the risk of having significant stenosis in coronary vasculature. Subjects with severe coronary artery stenosis scored higher on depression-dejection and anger-hostility sub-scales at the post angiography time period relative to pre-angiography scores. Trait and state anxiety levels were found to be moderate higher in both groups. PMID- 26160203 TI - Assessment of cytokine levels and hs-CRP in bipolar I disorder before and after treatment. AB - We aimed to assess the relationship between cytokine levels and the severity of the manic period in medication free patients. 30 Medication free patients and 28 healthy subjects (HS) were recruited. Plasma levels of pro-inflammatory, anti inflammatory, inflammatory cytokines, and hs-CRP levels were investigated upon hospital admission, after six weeks follow up in bipolar disease manic episode and the results were compared to HS. The severity of the manic episodes was assessed according to the Young mania rating scale. TNF-alpha, INF-gamma, IL-6 and hs-CRP levels were significantly higher in patients with manic episode of bipolar I disorder before treatment than HS. After treatment the levels of TNF alpha, INF-gamma, IL-6 and hs-CRP were observed to be significantly decreased. There was no difference between the levels of anti-inflammatory cytokines in patients before or after treatment of bipolar disorder and HS. hs-CRP was observed to be the only parameter correlated with clinical response. The most significant outcome of this study is the correlation between clinical outcome and hs-CRP levels in treatment naive manic episode bipolar type I patients. hs-CRP is the most consistent indicator according to pro-inflammatory, inflammatory and anti-inflammatory cytokines, in predicting treatment outcomes. PMID- 26160204 TI - Plasma brain-derived neurotrophic factor levels in patients suffering from post traumatic stress disorder. AB - A number of studies have been done to investigate the role of brain-derived neurotrophic factor (BDNF) in patients with post-traumatic stress disorder (PTSD). In this study we aimed to test the relationship between plasma BDNF levels and PTSD. We solicited 65 subjects having recently experienced road traffic accidents (RTA) conforming to screening criteria. They were given follow up examinations after one month, three months, and six months. PTSD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R TR, American Psychiatric Association, 2000) using the Mini International Neuropsychiatric Interview (MINI). All participants were divided into two groups: a group with PTSD and a group without PTSD. There were no significant differences in plasma BDNF levels between the two groups at either the 48h or six-month examination. Within the PTSD group, no significant differences were found in plasma BDNF levels between the two examinations. BDNF levels in those without PTSD showed a higher trend over time after trauma. Higher BDNF levels may be an important protective factor for the prevention of traumatized subjects from developing PTSD. PMID- 26160205 TI - The impact of revised DSM-5 criteria on the relative distribution and inter-rater reliability of eating disorder diagnoses in a residential treatment setting. AB - This study evaluated the relative distribution and inter-rater reliability of revised DSM-5 criteria for eating disorders in a residential treatment program. Consecutive adolescent and young adult females (N=150) admitted to a residential eating disorder treatment facility were assigned both DSM-IV and DSM-5 diagnoses by a clinician (n=14) via routine clinical interview and a research assessor (n=4) via structured interview. We compared the frequency of diagnostic assignments under each taxonomy and by type of assessor. We evaluated concordance between clinician and researcher assignment through inter-rater reliability kappa and percent agreement. Significantly fewer patients received either clinician or researcher diagnoses of a residual eating disorder under DSM-5 (clinician-12.0%; researcher-31.3%) versus DSM-IV (clinician-28.7%; researcher-59.3%), with the majority of reassigned DSM-IV residual cases reclassified as DSM-5 anorexia nervosa. Researcher and clinician diagnoses showed moderate inter-rater reliability under DSM-IV (kappa=.48) and DSM-5 (kappa=.57), though agreement for specific DSM-5 other specified feeding or eating disorder (OSFED) presentations was poor (kappa=.05). DSM-5 revisions were associated with significantly less frequent residual eating disorder diagnoses, but not with reduced inter-rater reliability. Findings support specific dimensions of clinical utility for revised DSM-5 criteria for eating disorders. PMID- 26160206 TI - The association of suicide risk with negative life events and social support according to gender in Asian patients with major depressive disorder. AB - We investigated the associations between negative life events, social support, depressive and hostile symptoms, and suicide risk according to gender in multinational Asian patients with major depressive disorder (MDD). A total of 547 outpatients with MDD (352 women and 195 men, mean age of 39.58+/-13.21 years) were recruited in China, South Korea, Malaysia, Singapore, Thailand, and Taiwan. All patients were assessed with the Mini-International Neuropsychiatric Interview, the Montgomery-Asberg Depression Rating Scale, the Symptoms Checklist 90-Revised, the Multidimensional Scale of Perceived Social Support, and the List of Threatening Experiences. Negative life events, social support, depressive symptoms, and hostility were all significantly associated with suicidality in female MDD patients. However, only depressive symptoms and hostility were significantly associated with suicidality in male patients. Depression severity and hostility only partially mediated the association of negative life events and poor social support with suicidality in female patients. In contrast, hostility fully mediated the association of negative life events and poor social support with suicidality in male patients. Our results highlight the need of in-depth assessment of suicide risk for depressed female patients who report a number of negative life events and poor social supports, even if they do not show severe psychopathology. PMID- 26160207 TI - Vulnerability for mania - is it linked to problems delaying gratification? AB - Impulsivity is described as one of the main risk factors for mania. One facet of impulsivity, the inability to delay gratification, might be of special relevance, because a hypersensitivity to reward is hypothesized to be related to mania. The main aim of this study was to examine whether risk for mania is associated with deficits in the ability to delay gratification using both a behavioral and a self report (UPPS) measure. An additional reason for choosing the UPPS was to see if prior results about an association between risk for mania and positive urgency could be replicated. Thirty-three individuals at risk for mania and a matched control group were selected using the Hypomanic Personality Scale and interviewed for a history of mood disorders. The main outcome measures were the Single-Key Impulsivity-Paradigm and Monetary Choice Questionnaire. The groups did not differ in measures of gratification delay but we replicated other studies reporting significantly higher levels of positive urgency and sensation seeking in at-risk individuals. We suggest that individuals at risk might not generally be more impulsive but rather that impulsive behaviors might be triggered in response to specific mood states. PMID- 26160208 TI - SLC6A14 and 5-HTR2C polymorphisms are associated with food intake and nutritional status in children. AB - BACKGROUND: Serotonin plays a critical role in the regulation of food intake. The solute carrier family 6 member 14 (SLC6A14) and serotonin receptor 2C (5-HTR2C) genes are involved in the bioavailability and action of this neurotransmitter. OBJECTIVE: Evaluation of the association of six polymorphisms in these genes with food intake and nutritional status in children followed to 7-8years of age. DESIGN: Blood samples and the biodemographic data of 344 children were collected at three development stages, in a cross-sectional study undertaken with the cohort from a randomized trial. Polymorphisms were analyzed using polymerase chain reaction-based techniques. RESULTS: At 7 to 8years of age, carriers of the A alleles for both the SLC6A14 rs2312054 and SLC6A14 rs12391221 polymorphisms showed higher food intake, except for the sugar-dense food (SDF) intake parameter, than T/T and C/C homozygotes, respectively. Boy carriers of the C allele of rs2071877 had a higher sum of triceps and subscapular folds than T allele carriers at 7 to 8years old. For 5-HTR2C gene variants, A allele carriers (rs3813928) and T allele carriers (rs3813929) had higher food intake at 3 to 4years old than G/G and C/C homozygotes, respectively, except for SDF. At this age, the intake of energy-dense foods was higher in carriers of the T allele (rs3813929) than in C/C homozygotes. CONCLUSION: This study provides evidence that genetic variants of these proteins might be involved in the determination of food intake and nutritional status in children. PMID- 26160209 TI - Falsely elevated tacrolimus concentrations on the Dimension Xpand. PMID- 26160210 TI - Mechanism of Procedural Stroke Following Carotid Endarterectomy or Carotid Artery Stenting Within the International Carotid Stenting Study (ICSS) Randomised Trial. AB - OBJECTIVE: To decrease the procedural risk of carotid revascularisation it is crucial to understand the mechanisms of procedural stroke. This study analysed the features of procedural strokes associated with carotid artery stenting (CAS) and carotid endarterectomy (CEA) within the International Carotid Stenting Study (ICSS) to identify the underlying pathophysiological mechanism. MATERIALS AND METHODS: Patients with recently symptomatic carotid stenosis (1,713) were randomly allocated to CAS or CEA. Procedural strokes were classified by type (ischaemic or haemorrhagic), time of onset (intraprocedural or after the procedure), side (ipsilateral or contralateral), severity (disabling or non disabling), and patency of the treated artery. Only patients in whom the allocated treatment was initiated were included. The most likely pathophysiological mechanism was determined using the following classification system: (1) carotid-embolic, (2) haemodynamic, (3) thrombosis or occlusion of the revascularised carotid artery, (4) hyperperfusion, (5) cardio-embolic, (6) multiple, and (7) undetermined. RESULTS: Procedural stroke occurred within 30 days of revascularisation in 85 patients (CAS 58 out of 791 and CEA 27 out of 819). Strokes were predominately ischaemic (77; 56 CAS and 21 CEA), after the procedure (57; 37 CAS and 20 CEA), ipsilateral to the treated artery (77; 52 CAS and 25 CEA), and non-disabling (47; 36 CAS and 11 CEA). Mechanisms of stroke were carotid-embolic (14; 10 CAS and 4 CEA), haemodynamic (20; 15 CAS and 5 CEA), thrombosis or occlusion of the carotid artery (15; 11 CAS and 4 CEA), hyperperfusion (9; 3 CAS and 6 CEA), cardio-embolic (5; 2 CAS and 3 CEA) and multiple causes (3; 3 CAS). In 19 patients (14 CAS and 5 CEA) the cause of stroke remained undetermined. CONCLUSION: Although the mechanism of procedural stroke in both CAS and CEA is diverse, haemodynamic disturbance is an important mechanism. Careful attention to blood pressure control could lower the incidence of procedural stroke. PMID- 26160211 TI - Adjustable Velcro Compression Devices are More Effective than Inelastic Bandages in Reducing Venous Edema in the Initial Treatment Phase: A Randomized Controlled Trial. AB - OBJECTIVE/BACKGROUND: The objective of this study was to compare the efficacy and comfort of inelastic bandages (IBs) and adjustable Velcro compression devices (AVCDs) in reducing venous leg edema in the initial treatment phase. METHODS: Forty legs from 36 patients with untreated venous edema (C3EpsAsdPr) were randomized to two groups. Patients in the first group received IBs (n = 20) and those in the second AVCDs (n = 20). Both compression devices were left on the leg day and night, and were renewed after 1 day. Patients in the AVCD group were asked to re-adjust the device as needed when it felt loose. Leg volume was calculated using the truncated cone formula at baseline (T0), after 1 day (T1) and after 7 days (T7). The interface pressure of the two compression devices was measured by an air filled probe, and the static stiffness index calculated after applying compression at T0 and T1, and just before removal of compression on T1 and T7. Patient comfort with regard to the two compression systems was assessed by grading signs and symptoms using a visual analog scale. RESULTS: At T1, the median percent volume reduction was 13% for the IB group versus 19% for the AVCD group; at T7 it was 19% versus 26%, respectively (p < .001). The pressure of the IBs was significantly higher compared with the AVCDs at T0 (63 vs. 43 mmHg) but dropped by > 50% over time, while it remained unchanged with AVCDs owing to the periodic readjustment by the patient. Comfort was reported to be similar with the two compression devices. CONCLUSION: Re-adjustable AVCDs with a resting pressure of around 40 mmHg are more effective in reducing chronic venous edema than IBs with a resting pressure of around 60 mmHg. AVCDs are effective and well tolerated, not only during maintenance therapy, but also in the initial decongestive treatment phase of patients with venous leg edema. PMID- 26160212 TI - IL10-Deficiency in CD4+ T Cells Exacerbates the IFNgamma and IL17 Response During Bacteria Induced Colitis. AB - BACKGROUND/AIMS: IL10 is a key inhibitor of effector T cell activation and a mediator of intestinal homeostasis. In addition, IL10 has emerged as a key immunoregulator during infection with various pathogens, ameliorating the excessive T-cell responses that are responsible for much of the immunopathology associated with the infection. Because IL10 plays an important role in both intestinal homeostasis and infection, we studied the function of IL10 in infection-associated intestinal inflammation. METHODS: Wildtype mice and mice deficient in CD4+ T cell-derived or regulatory T cells-derived IL10 were infected with the enteric pathogen Citrobacter (C.) rodentium and analyzed for the specific immune response and pathogloy in the colon. RESULTS: We found that IL10 expression is upregulated in colonic tissue after infection with C. rodentium, especially in CD4+ T cells, macrophages and dendritic cells. Whereas the deletion of IL10 in regulatory T cells had no effect on C. rodentium induced colitis, infection of mice deficient in CD4+ T cell-derived IL10 exhibited faster clearance of the bacterial burden but worse colitis, crypt hyperplasia, and pathology than did WT mice. In addition, the depletion of CD4+ T cell-derived IL10 in infected animals was accompanied by an accelerated IFNgamma and IL17 response in the colon. CONCLUSION: Thus, we conclude that CD4+ T cell-derived IL10 is strongly involved in the control of C. rodentium-induced colitis. Interference with this network could have implications for the treatment of infection-associated intestinal inflammation. PMID- 26160214 TI - Characteristics of chlamydia-like organisms pathogenic to fish. AB - Bacteria from the Chlamydiales order have been long known, especially as pathogenic bacteria to humans and many animal species, principally including birds and mammals. But for slightly over 20 years, they have been identified in the aquatic environment as endosymbionts of amoebas and sea worms. For several years, they have also been recorded as a cause of diseases among fish, causing respiratory system infections in the form of epitheliocystis of the gill. At present, 11 chlamydia-like organisms pathogenic to fish have been described, including nine new ones, classified into six families, four of which are already known (Parachlamydiaceae, Rhabdochlamydiaceae, Candidatus Parilichlamydiaceae, Candidatus Clavichlamydiaceae) and two newly created families, namely Candidatus Actinochlamydiaceae and Candidatus Parilichlamydiaceae. This paper characterises 11 chlamydia-like organisms, as well as seven isolates not classified into families, which are pathogenic to fish, presenting their genetical properties allowing for their classification, as well as morphological properties and diseases caused. PMID- 26160213 TI - Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus. AB - Liver disease (LD), defined as >= 2-fold elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT), was examined in a longitudinal study of systemic lupus erythematosus (SLE) patients. Among 435 patients, 90 (20.7%) had LD with a greater prevalence in males (15/39; 38.5%) than females (75/396; 18.9%; p = 0.01). SLE disease activity index (SLEDAI) was greater in LD patients (7.8 +/ 0.7) relative to those without (5.8 +/- 0.3; p = 0.0025). Anti-smooth muscle antibodies, anti-DNA antibodies, hypocomplementemia, proteinuria, leucopenia, thrombocytopenia, and anti-phospholipid syndrome were increased in LD. An absence of LD was noted in patients receiving rapamycin relative to azathioprine, cyclosporine A, or cyclophosphamide. An absence of LD was also noted in patients treated with N-acetylcysteine. LFTs were normalized and SLEDAI was diminished with increased prednisone use in 76/90 LD patients over 12.1 +/- 2.6 months. Thus, LD is attributed to autoimmunity and disease activity, it responds to prednisone, and it is potentially preventable by rapamycin or N-acetylcysteine treatment. PMID- 26160221 TI - Increasing physical activity in office workers--the Inphact Treadmill study; a study protocol for a 13-month randomized controlled trial of treadmill workstations. AB - BACKGROUND: Sedentary behaviour is an independent risk factor for mortality and morbidity, especially for type 2 diabetes. Since office work is related to long periods that are largely sedentary, it is of major importance to find ways for office workers to engage in light intensity physical activity (LPA). The Inphact Treadmill study aims to investigate the effects of installing treadmill workstations in offices compared to conventional workstations. METHODS/DESIGN: A two-arm, 13-month, randomized controlled trial (RCT) will be conducted. Healthy overweight and obese office workers (n = 80) with mainly sedentary tasks will be recruited from office workplaces in Umea, Sweden. The intervention group will receive a health consultation and a treadmill desk, which they will use for at least one hour per day for 13 months. The control group will receive the same health consultation, but continue to work at their regular workstations. Physical activity and sedentary time during workdays and non-workdays as well as during working and non-working hours on workdays will be measured objectively using accelerometers (Actigraph and activPAL) at baseline and after 2, 6, 10, and 13 months of follow-up. Food intake will be recorded and metabolic and anthropometric variables, body composition, stress, pain, depression, anxiety, cognitive function, and functional magnetic resonance imaging will be measured at 3-5 time points during the study period. Interviews with participants from the intervention group will be performed at the end of the study. DISCUSSION: This will be the first long-term RCT on the effects of treadmill workstations on objectively measured physical activity and sedentary time as well as other body functions and structures/morphology during working and non-working hours among office workers. This will provide further insight on the effects of active workstations on our health and could fill in some of the knowledge gaps regarding how we can reduce sedentary time in office environments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01997970, 2nd Nov 2013. PMID- 26160222 TI - LTD, RP, and Motor Learning. AB - Long-term depression (LTD) at excitatory synapses between parallel fibers and a Purkinje cell has been regarded as a critical cellular mechanism for motor learning. However, it was demonstrated that normal motor learning occurs under LTD suppression, suggesting that cerebellar plasticity mechanisms other than LTD also contribute to motor learning. One candidate for such plasticity is rebound potentiation (RP), which is long-term potentiation at inhibitory synapses between a stellate cell and a Purkinje cell. Both LTD and RP are induced by the increase in postsynaptic Ca(2+) concentration, and work to suppress the activity of a Purkinje cell. Thus, LTD and RP might work synergistically, and one might compensate defects of the other. RP induction is dependent on the interaction between GABAA receptor and GABAA receptor binding protein (GABARAP). Transgenic mice expressing a peptide which inhibits binding of GABARAP and GABAA receptor only in Purkinje cells show defects in both RP and adaptation of vestibulo-ocular reflex (VOR), a motor learning paradigm. However, another example of motor learning, adaptation of optokinetic response (OKR), is normal in the transgenic mice. Both VOR and OKR are reflex eye movements suppressing the slip of visual image on the retina during head movement. Previously, we reported that delphilin knockout mice show facilitated LTD induction and enhanced OKR adaptation, but we recently found that VOR adaptation was not enhanced in the knockout mice. These results together suggest that animals might use LTD and RP differently depending on motor learning tasks. PMID- 26160223 TI - Collisional dynamics in a gas of molecular super-rotors. AB - Recently, femtosecond laser techniques have been developed that are capable of bringing gas molecules to extremely fast rotation in a very short time, while keeping their translational motion relatively slow. Here we study collisional equilibration dynamics of this new state of molecular gases. We show that the route to equilibrium starts with a metastable 'gyroscopic stage' in the course of which the molecules maintain their fast rotation and orientation of the angular momentum through many collisions. The inhibited rotational-translational relaxation is characterized by a persistent anisotropy in the molecular angular distribution, and is manifested in the optical birefringence and anisotropic diffusion in the gas. After a certain induction time, the 'gyroscopic stage' is abruptly terminated by an explosive rotational-translational energy exchange, leading the gas towards the final equilibrium. We illustrate our conclusions by direct molecular dynamics simulation of several gases of linear molecules. PMID- 26160224 TI - From Blue to Green: The Development and Implementation of a Therapeutic Horticulture Program for Residents of a Battered Women's Shelter. AB - The delivery of therapeutic services to clients is influenced by service providers' understanding of the "fit" of a specific program with their service mandate as well as their perceptions of the potential benefits of the program. This article discusses the development and implementation of a therapeutic horticulture (TH) program at a battered women's shelter that serves 17 counties in Central Kentucky. Through semistructured interviews, we gauge the shelter staff's perceptions of the relationship of the TH program to the shelter's overall mission; their sense of the program's benefits for residents, for the shelter as a community organization, and for themselves; and their concerns about the TH program. We consider how these findings may impact future programming at the shelter, and we discuss plans for further evaluation of the TH program in terms of its impact on shelter residents' long-term outcomes. PMID- 26160225 TI - MicroRNA-23a enhances migration and invasion through PTEN in osteosarcoma. AB - To investigate the biological significance of abundant microRNA-23a (miR-23a) expression in osteosarcoma and its correlation with PTEN in the pathogenesis of osteosarcoma migration and invasion. The human osteosarcoma cell lines MG63, HOS58 and SaoS-2, and the human normal osteoblasts (hFOB1.19) were grown in RPMI 1640 medium supplemented with 10% fetal bovine serum. Gene and protein levels of miR-23a and PTEN were examined to determine the molecular relationship between them in the pathogenesis of osteosarcoma. Inhibition of miR-23a effectively reduced migration and invasion of osteosarcoma cell lines. Bioinformatics and luciferase-reporter assay revealed that miR-23a specifically targeted the 3' untranslational region of PTEN and regulated its expression. Downregulation of PTEN enhanced migration and invasion of osteosarcoma cell lines. Furthermore, in tumor tissues obtained from osteosarcoma patients, the expression of miR-23a was negatively correlated with PTEN and the high expression of miR-23a combined with low expression of PTEN might serve as a risk factor for cancer patients. Besides, miR-23a-mediated suppression of PTEN led to activation of AKT/ERK pathways and epithelial-mesenchymal transition (EMT) in osteosarcoma cells, and finally enhanced the activity of osteosarcoma cell proliferation and movement and promoted osteosarcoma xenograft tumor growth in mouse models. Our study showed that miR-23a, by downregulation of PTEN, enhanced migration and invasion in osteosarcoma cells. PMID- 26160226 TI - Planning and self-efficacy interventions encouraging replacing energy-dense foods intake with fruit and vegetable: A longitudinal experimental study. AB - OBJECTIVE: This longitudinal experimental study compared effects of self efficacy, planning and education-based conditions, encouraging adolescents to eat fruit and vegetable in place of energy-dense foods. DESIGN: Data were collected among 506 adolescents (13-18 years old) who were randomly assigned to control (n = 181), planning (n = 153) or self-efficacy (n = 172) conditions. Measurements were taken at baseline (T1), at a 2-month follow-up (T2), and at a 14-month follow-up (T3). Interventions/control group procedures were delivered at T1 and T2. OUTCOME MEASURES: Self-reports of fruit and vegetable intake (FVI) and energy dense foods intake were collected at three times. Cognitive mediators (self efficacy and planning) were assessed at T1 and T2. Body weight and height were objectively measured at T1 and T3. RESULTS AND CONCLUSIONS: Similar significant increases of FVI were found for planning and self-efficacy interventions (T3). The planning intervention did not influence energy-dense food intake (T3), but the self-efficacy intervention tended to result in stabilising intake (compared to an increase found in the control group). There were no effects on body weight. Similar patterns were found for the total sample and for a subsample of adolescents with overweight/obesity. The effects of interventions on FVI were mediated by respective cognitions. PMID- 26160227 TI - Effect of locomotion score on sows' performances in a feed reward collection test. AB - Sows housed in groups have to move through their pen to fulfil their behavioural and physiological needs such as feeding and resting. In addition to causing pain and discomfort, lameness may restrict the ability of sows to fulfil such needs. The aim of our study was to investigate the extent to which the mobility of sows is affected by different degrees of lameness. Mobility was measured as the sow's willingness or capability to cover distances. Feed-restricted hybrid sows with different gait scores were subjected to a feed reward collection test in which they had to walk distances to obtain subsequent rewards. In all, 29 group-housed sows at similar gestation stage (day 96.6 +/- 7 s.d.) were visually recorded for gait and classified as non-lame, mildly lame, moderately lame or severely lame. All sows received 2.6 kg of standard commercial gestation feed per day. The test arena consisted of two feeding locations separated from each other by a Y-shaped middle barrier. Feed rewards were presented at the two feeders in turn, using both light and sound cues to signal the availability of a new feed reward. Sows were individually trained during 5 non-consecutive days for 10 min/day with increasing barrier length (range: 0 to 3.5 m) each day. After training, sows were individually tested once per day on 3 non-consecutive days with the maximum barrier length such that they had to cover 9.3 m to walk from one feeder to the other. The outcome variable was the number of rewards collected in a 15-min time span. Non-lame and mildly lame sows obtained more rewards than moderately lame and severely lame sows (P<0.01). However, no significant difference was found between non-lame and mildly lame sows (P=0.69), nor between moderately lame and severely lame sows (P=1.00). This feed reward collection test indicates that both moderately lame and severely lame sows are limited in their combined ability and willingness to walk, but did not reveal an effect of mild lameness on mobility. These findings suggest that moderately and more severely lame sows, but not mildly lame sows, might suffer from reduced access to valuable resources in group housing systems. PMID- 26160228 TI - Transient branch retinal artery occlusion in a 15-year-old girl and review of the literature. AB - BACKGROUND: Retinal artery occlusion is an extremely rare diagnosis in the pediatric population and the etiology with risk factors of retinal artery occlusion are poorly understood in younger individuals. METHODS AND RESULTS: This case report a rare case of transient branch retinal artery occlusion (BRAO) in a healthy young girl. A fifteen-year-old girl presented with painless decreased vision in her right eye. Fundus examination revealed in the right eye intensive edema of the part of superior half of the retina, but the vessels were absolutely normal. She was hospitalized for diagnosis and treatment. A thorough workup was performed to determine any etiologic factor. Her physical examination was normal, but from anamnesis has been found that patient began use oral contraception at the time of occurrence eye problems. The condition is evaluated as transient branch retinal artery occlusion by the course of the disease. The paper includes the review of the literature also. CONCLUSION: Though retinal arterial obstruction is rare in the pediatric population, this case highlights the importance of including this in the differential diagnosis of acute vision loss. PMID- 26160229 TI - A new modified technique for the treatment of high-risk prethreshold ROP under the direct visual control of RetCam 3. AB - PURPOSE: To describe a new modified technique in the treatment of ROP (retinopathy of prematurity) using the RetCam 3 digital imaging system - Camera Assisted Laser photocoagulation and Cryotherapy of the Retina (CALCR). METHODS: From Nov 2011 to Oct 2013, 113 infants were diagnosed with ROP. The average post conceptual age (PCA) at the time of diagnosis was the 35(th) week of PCA; the average birth weight was 1,041 g. According to the ETROP study, the avascular part of the retina of infants with high-risk prethreshold ROP was treated with a trans-scleral diode laser or with cryotherapy within 48-72 h after the diagnosis. The intervention was performed under general anaesthesia under the direct visual control of the RetCam 3. RESULTS: The CALCR technique was used in all 23 infants (46 eyes) diagnosed with high-risk prethreshold ROP. The average age of these infants at the time of the intervention was the 38(th) week of PCA. None of the infants had any serious complications during the CALCR procedure. In contrast to the traditional technique, CALCR offers many benefits: the image of the retina is real, magnified and not inverted, it shows details of the retina in a high resolution, photo and video documentation is available. Therefore the preoperative, intraoperative and postoperative condition of the retina can be precisely evaluated and compared on a fully standardized basis. CONCLUSIONS: The CALCR procedure represents a new technique providing greater accuracy when targeting the avascular part of the retina, enables better visualisation and more precise treatment, and reduces the risk of unintended damage to healthy retinal tissue. PMID- 26160230 TI - Aflatoxin B1 in eggs and chicken livers by dispersive liquid-liquid microextraction and HPLC. AB - A rapid, low-cost and simple technique has been developed for the determination of aflatoxin B1 (AFB1) in eggs and livers using high-performance liquid chromatography (HPLC) with UV detection. In this study, the presence of AFB1 was investigated in 150 eggs and 50 chicken livers from the local market of Tabriz, Iran. AFB1 was extracted with a mixture of acetonitrile:water (80:20) and cleaned up by dispersive liquid-liquid microextraction which is a very economical, fast and sensitive method. AFB1 was quantified by HPLC-UV without need for any complex derivatisation in samples to enhance the detection. The results showed that 72% of the liver and 58% of the egg samples were contaminated with AFB1 ranging from 0.30 to 16.36 ug kg (1). limit of detection and limit of quantification for AFB1 were 0.08 and 0.28 ug kg ( 1), respectively. The proposed method is suitable for fast analysing of AFB1 in egg and liver samples. PMID- 26160231 TI - Lagged influence of North Atlantic Oscillation on population dynamics of a Mediterranean terrestrial salamander. AB - The North Atlantic Oscillation (NAO) is a large-scale climatic pattern that strongly influences the atmospheric circulation in the northern Hemisphere and by consequence the long-term variability of marine and terrestrial ecosystem over great part of northern Europe and western Mediterranean. In the Mediterranean, the effects of the NAO on vertebrates has been studied mainly on bird populations but was rarely analysed in ectothermic animals, and in particular in amphibians. In this study, we investigated the relationships between winter, spring and summer NAO indexes and the long-term population dynamics of the plethodontid salamander Speleomantes strinatii. This terrestrial salamander was monitored inside an artificial cave in NW Italy for 24 consecutive years. The relationships between seasonal NAO indexes and the salamander dynamics were assessed by cross correlation function (CCF) analysis, after prewhitening the time series by autoregressive moving average statistical modelling. Results of CCF analyses indicated that the salamander abundance varied in relation to the one-year ahead winter NAO (P = 0.018), while no relationships were found with spring and summer indexes. These results strengthen some previous findings that suggested a high sensitivity of temperate terrestrial amphibians to wintertime climatic conditions. PMID- 26160232 TI - Collaboration in the competitive world of science: lessons to be learned from William T. Keeton. AB - The tremendous increase in the number of authors and institutional affiliations on papers published in the natural sciences over the last few decades is commonly interpreted as an indicator of an increase in the collaborative spirit. However, a closer analysis suggests that this development reflects an increase in cooperation (defined as a strategy to divide labor among participants), rather than a rise in collaboration (defined as a mutual engagement of participants in a coordinated effort to jointly solve a problem). An exception to this development was William T. Keeton (1933-1980), who, as a faculty member at Cornell University, pioneered research into pigeon homing. A direct result of his willingness to openly share ideas and collaborate with other investigators is the article by Hagstrum and Manley (J Comp Physiol A, 2015) in this issue of the Journal of Comparative Physiology A. Their study is based on data from experiments Keeton and his collaborators conducted some 40 years ago. Despite the age of these data, their analysis and the interpretation of the results are likely to stimulate fruitful discussion in the field of avian orientation. PMID- 26160234 TI - Cultural Factors Associated with Breast and Cervical Cancer Screening in Korean American Women in the US: An Integrative Literature Review. AB - PURPOSE: This study examined current research theories and methods, cultural factors, and culturally relevant interventions associated with breast and cervical cancer screening in Korean American (KA) women. METHODS: Based on Ganong's guidelines, the literature on cultural factors associated with breast and cervical cancer screening in KA women was searched using MEDLINE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Sixty-eight articles on breast cancer screening and 66 articles on cervical cancer screening were retrieved from both databases, and a total of 22 articles were included in the literature review based on the selection criteria. RESULTS: Of the 22 studies reviewed, 14 (63.6%) were descriptive and 8 (36.4%) were interventional. Many studies have used individual focused cognitive theories such as health belief model and different types of operationalization for measures of cultural beliefs. Cultural factors associated with breast and cervical cancer screening in KA women that were identified in descriptive quantitative and qualitative studies included family, embarrassment, preventive health orientation, fatalism, and acculturation. Most culturally relevant interventional studies used education programs, and all education was conducted by bilingual and bicultural health educators at sociocultural sites for KA women. CONCLUSIONS: Theories focusing on interpersonal relationships and standardized, reliable, and valid instruments to measure cultural concepts are needed to breast and cervical cancer screening research in KA women. Traditional cultural factors associated with cancer screening should be considered for practical implications and future research with KA women. PMID- 26160235 TI - Conditions and Patterns of Intimate Partner Violence among Taiwanese Women. AB - PURPOSE: Intimate partner violence (IPV) is a serious public health issue among women. IPV victims usually seek help from hospitals, and emergency nurses are the frontline staff with whom the victims come into contact first. This study examined the conditions and patterns of IPV in southern Taiwan. METHODS: From designated hospitals in Kaohsiung under the Department of Health Injury Assessment Clinic, data were collected on 497 women regarding their injury assessment for IPV reported to the Kaohsiung City Government. RESULTS: Taiwanese survivors were older compared to immigrant survivors. Taiwanese survivors also had higher education levels compared to immigrant survivors. Taiwanese survivors had higher employment rate than immigrant survivors did. The time between IPV and medical help seeking was longer for divorced than married women. CONCLUSIONS: These results can facilitate understanding of the conditions and patterns of IPV in Taiwan, increase the awareness of nurses, especially the emergency nurses for the prevention of IPV, and increase professional competency for the provision of appropriate healthcare services to survivors of IPV. PMID- 26160236 TI - A Study on Body Image, Sexual Quality of Life, Depression, and Quality of Life in Middle-aged Adults. AB - PURPOSE: The purpose of this study was to examine the correlations of body image, sexual quality of life (SQOL), depression, and quality of life, and to identify the influencing factors on quality of life of middle-aged adults in the community. METHODS: The participants of this study were 367 middle-aged adults. Data were collected through personal interviews using a questionnaire. Data were analyzed using descriptive statistics, t tests, one-way analysis of variance, Pearson's correlation coefficients, and stepwise multiple regression. RESULTS: Body image, SQOL, depression, and quality of life according to the general characteristics and health-related characteristics commonly showed significant differences in age, level of education, duration of marriage, living arrangement, occupation, monthly income, presence of disease, exercise, stressor, frequency of sexual intercourse with spouse, and degree of deep sleep. Quality of life showed significant positive correlations with body image and SQOL, but a significantly negative correlation with depression. Body image, depression, education level, SQOL, and stressor, which accounted for 42.0% of the variance, were significant predictors influencing quality of life in middle-aged adults in the community. CONCLUSIONS: To improve quality of life in middle-aged adults ahead of old age, an assessment of their body image, depression, SQOL should be made and a variety of nursing interventions should be followed to improve their positive body image, depression, and SQOL. PMID- 26160237 TI - Parenting Efficacy and Health-promoting Behaviors for Children of Mothers from Native and Multicultural Families in Korea. AB - PURPOSE: The aim of this study was to examine the levels of parenting efficacy and health-promoting behaviors for children of mothers, and to explore the relationships between parenting efficacy and the behaviors of mothers from native and multicultural families in South Korea. METHODS: Data was collected by a self report questionnaire completed by 258 mothers who had 6-month to 36-month-old children attending kindergartens or multicultural family support centers located in Seoul and in Gyeounggi Province, South Korea. RESULTS: No significant difference in parenting efficacy was found, depending on the maternal country of origin. However, Chinese mothers performed health-promoting behaviors more frequently for their children than Korean and Vietnamese mothers did (F = 6.87, p < .001). The significant positive correlations between parenting efficacy and maternal health-promoting behaviors for children were found, regardless of maternal country of origin (r = .57, p < .001 for Korean, r = .42, p < .001 for Chinese, and r= .40, p < .001 for Vietnamese mothers). CONCLUSIONS: Since maternal health-promoting behaviors were different depending on the native country of the mothers, maternal country of origin should be considered in designing programs for improving maternal health-promoting behaviors for their children. In addition, increasing the level of parenting efficacy can be an effective way for improvement of maternal health-promoting behaviors. PMID- 26160238 TI - Clinical Experiences as Related to Standard Precautions Compliance among Nursing Students: A Focus Group Interview Based on the Theory of Planned Behavior. AB - PURPOSE: During clinical placements, nursing students who come into close contact with patients and provide nursing interventions may be exposed to harmful pathogens. However, little is known about nursing students' experiences with standard precautions (SP) in clinical settings. METHODS: We conducted interviews with six focus groups of nursing students (n = 38) from two universities in South Korea. The focus group interviews each took 90-120 minutes and included 6-7 participants from two different universities. The meetings used semi-structured interview protocols. Qualitative content analysis was employed. RESULTS: Four themes and 9 subthemes were identified: (a) attitudes (knowledge deficit, sensitivity), (b) subjective norms (negative role models, classroom and in-field gaps, blind spots), (c) perceived behavioral control (psychological barriers, physical barriers, lack of information), and (d) intention (changes in compliance awareness). CONCLUSIONS: These focus groups revealed that many nursing students worked in vulnerable environments and risked pathogen exposure. Nursing students expressed the importance of SP but reported witnessing many instances of failure to comply with established measures. Several barriers were explored as reasons of SP noncompliance. By removing the barriers presented in this study, nursing students would be able to perform their duties in a safe clinical environment. PMID- 26160239 TI - Factors Associated with Early Smoking Initiation among Korean Adolescents. AB - PURPOSE: The aim of this study was to identify factors associated with early initiation of cigarette smoking among Korean adolescents. METHODS: A secondary analysis was conducted on the 2012 Korea Youth Risk Behavior Web-based Survey data using Cox proportional hazards regression. RESULTS: Early smoking initiation was associated with being male, having a positive subjective health status, perceiving oneself as thin or average weight (body image), having an average happiness level, being stressed, consuming alcohol, having suicidal ideation, experiencing sexual intercourse, having low or average academic grades, having a parental education level of high school or below, not taking a family trip in the previous 12 months, and having a family that approves of smoking in the home. CONCLUSIONS: Interventions targeting the prevention of smoking initiation among adolescents should include individual factors such as health status, body weight, perceived mental health status, health-risk behaviors, and academic characteristics as well as family factors that reinforce family cohesion and home smoking bans. Moreover, male adolescents aged 12-13 years and their parents should be the main target of these interventions. PMID- 26160240 TI - Association of Personality Traits and Risk of Internet Addiction in Adolescents. AB - PURPOSE: This cross-sectional, descriptive study analyzes the association between personality traits and internet addiction in adolescents. METHODS: The study was conducted with 328 adolescents attending two high schools in the Aegean region of Turkey. The data were collected using a sociodemographic information questionnaire, the Internet Addiction Scale and the Adjective Based Personality Scale from students who gave their informed consent to participate. Data were assessed by descriptive statistics, t tests, and logistic regression analysis, using SPSS software. RESULTS: The students had an average age of 16.43 +/- 1.47 years and 40.5% were female. The percentage of subjects at risk of internet addiction was 15.9% (n = 52), and 42.4% (n = 22) of them reported that the amounts of time they spent online was acceptable. We found statistically significant differences in the average subdimensional scores for extraversion (t = 2.310, p < .050) and openness to experience (t = 3.35, p < .001), and between students at risk of internet addiction (n = 52) and those who were not (n = 276). CONCLUSIONS: Adolescents who were found to be at risk of internet addiction nevertheless reported on the survey questionnaires that the amount of time they spent online was acceptable. The study determined that participants' risk of internet addiction was associated with their levels of extraversion and openness to experience. PMID- 26160241 TI - Effects of Health Status and Health Behaviors on Depression Among Married Female Immigrants in South Korea. AB - PURPOSE: This study examined the effects of health status and health behaviors on depression in married female immigrants in South Korea. METHODS: Sampling 316 immigrant women from the Philippines, Vietnam, China, and other Asian countries, a cross-sectional research design was used with self-report questionnaires that assessed sociodemographic characteristics, health status, health behaviors, and depression. RESULTS: There were significant differences in stillbirth experience, induced abortion, morbidity, perceived health status, meal skipping, and physical activity between depressed and nondepressed immigrant women. After adjusting for sociodemographic variables, stillbirth experience, poorer perceived health status, more meal skipping, and less physical activity were associated with greater depressive symptoms. CONCLUSIONS: Both health status and health behaviors had significant impacts on depression, suggesting that development of nursing interventions and educational programs should be targeted towards improving maternal health, healthy lifestyle, and subjective health perception to promote married female immigrants' psychological well-being. PMID- 26160242 TI - Characteristics and Factors Associated with Problem Drinking in Male Workers. AB - PURPOSE: This study aimed to identify the characteristics and factors related to problem drinking in male workers. METHODS: This study was conducted using a cross sectional survey and 232 male workers, who completed self-reported questionnaires addressing alcohol consumption, drinking motives, job stress, supervisor/coworker support, and family support. Multivariate analysis was used to uncover factors associated with problem drinking. RESULTS: As compared with normal alcohol users, problem drinkers were more likely to smoke and had greater family support and coping motivations, and fewer confirmatory motives. Problem drinking was found to be related to perceived health status (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] [0.64, 0.95]), current smoking (adjusted OR = 2.79, 95% CI [1.26, 6.18]), family support (adjusted OR = 2.04, 95% CI [1.23, 3.39]), confirmatory motivation (adjusted OR = 0.60, 95% CI [0.37, 0.96]), and coping (adjusted OR = 1.79, 95% CI [1.04, 3.07]). CONCLUSIONS: Our findings suggest that any interventions targeting problem drinking among male workers must address smoking cessation, control of stress, and the improvement of drinking subculture in the workplace. PMID- 26160243 TI - Psychometric Properties of a Measure Assessing Attitudes and Norms as Determinants of Intention to Use Oral Contraceptives. AB - PURPOSE: Asian immigrant and Asian American women are less likely to use oral contraceptives (OCs) and tend to rely on low-efficacy methods of contraception. This contraceptive pattern remains poorly understood, in part, because no theory driven measurement exists to assess psychosocial determinants essential in explaining behaviors related to OC use in this population. The current study aimed to evaluate the psychometric properties of a measure of attitudes and subjective norms toward OC use among Korean American women as a first step to determine whether the measure can be used in this population and, potentially, in other Asian ethnic groups. METHODS: The sample consisted of 329 Korean immigrant women living in New York City. The theory of reasoned action guided the development of the measure assessing attitudes and norms. Psychometric evaluation included item analysis, internal consistency estimates of reliability, and construct validity (i.e., factorial, discriminant, and predictive). RESULTS: All item-total correlations were above the recommendation of .30. The Cronbach's alpha for the attitudes and subjective norms measure was .88 and .86, respectively. Exploratory factor analyses revealed four interpretable factors, and confirmatory factor analyses confirmed that the factor structures derived from the exploratory factor analyses fit the data well. Discriminant and predictive validity of the measure were also established. CONCLUSIONS: The study provides support for the validity and reliability of the measure and its use for determining the degree to which Korean immigrant women intend to use OCs. PMID- 26160244 TI - Anger Expression Types and Interpersonal Problems in Nurses. AB - PURPOSE: The purpose of this study was to investigate the anger expression types in nurses and to analyze the differences between the anger expression types and interpersonal problems. METHODS: The data were collected from 149 nurses working in general hospitals with 300 beds or more in Seoul or Gyeonggi province, Korea. For anger expression type, the anger expression scale from the Korean State-Trait Anger Expression Inventory was used. For interpersonal problems, the short form of the Korean Inventory of Interpersonal Problems Circumplex Scales was used. Data were analyzed using descriptive statistics, cluster analysis, multivariate analysis of variance, and Duncan's multiple comparisons test. RESULTS: Three anger expression types in nurses were found: low-anger expression, anger-in, and anger-in/control type. From the results of multivariate analysis of variance, there were significant differences between anger expression types and interpersonal problems (Wilks lambda F = 3.52, p < .001). Additionally, anger in/control type was found to have the most difficulty with interpersonal problems by Duncan's post hoc test (p < .050). CONCLUSIONS: Based on this research, the development of an anger expression intervention program for nurses is recommended to establish the means of expressing the suppressed emotions, which would help the nurses experience less interpersonal problems. PMID- 26160245 TI - Nurses' Educational Needs Assessment for Financial Management Education Using the Nominal Group Technique. AB - PURPOSE: The purpose of this study was to identify the financial management educational needs of nurses in order to development an educational program to strengthen their financial management competencies. METHODS: Data were collected from two focus groups using the nominal group technique. The study consisted of three steps: a literature review, focus group discussion using the nominal group technique, and data synthesis. RESULTS: After analyzing the results, nine key components were selected: corporate management and accounting, introduction to financial management in hospitals, basic structure of accounting, basics of hospital accounting, basics of financial statements, understanding the accounts of financial statements, advanced analysis of financial statements, application of financial management, and capital financing of hospitals. CONCLUSIONS: The present findings can be used to develop a financial management education program to strengthen the financial management competencies of nurses. PMID- 26160246 TI - Transtheoretical Model-based Nursing Intervention on Lifestyle Change: A Review Focused on Intervention Delivery Methods. AB - PURPOSE: The transtheoretical model (TTM) was used to provide tailored nursing for lifestyle management such as diet, physical activity, and smoking cessation. The present study aims to assess the provision of intervention delivery methods, intervention elements, and stage-matched interventions, in order to identify ways in which information technology is used in the TTM-based research. METHODS: The relevant literature was selected by two researchers using inclusion criteria after searching for "TTM (transtheoretical or stage of change)" and "nursing" from the databases PubMed and CINAHL. The selected studies were categorized in terms of study characteristics, intervention delivery method, intervention element, and use and level of stage-matched intervention. RESULTS: A total of 35 studies were selected including eight studies that used information communication technology (ICT). Nine different intervention delivery methods were used, of which "face-to-face" was the most common at 24 times. Of the 35 studies, 26 provided stage-matched interventions. Seven different intervention elements were used, of which "counseling" was the most common at 27 times. Of all the intervention elements, tailored feedback used ICT the most at seven instances out of nine, and there was a significant difference in the rate of ICT usage among intervention elements. CONCLUSIONS: ICT is not yet actively used in the TTM-based nursing interventions. Stage-matched interventions and TTM concepts were shown to be in partial use also in the TTM-based interventions. Therefore, it is necessary to develop a variety of ways to use ICT in tailored nursing interventions and to use TTM frameworks and concepts. PMID- 26160247 TI - Khmer American Mothers' Knowledge about HPV and HBV Infection and Their Perceptions of Parenting: My English Speaking Daughter Knows More. AB - PURPOSE: The purpose of this study is to explore and describe Khmer mothers' understanding of HBV and HPV prevention as well as their perception of parenting on health and health education of their daughters in the US. METHODS: The qualitative pilot study guided by the revised Network Episode Model and informed by ethnographic analysis and community-based purposive sampling method were used. Face-to-face audiotaped interviews with eight Khmer mothers were conducted by bilingual female middle-aged community health leaders who spoke Khmer. RESULTS: The findings revealed that Khmer mothers clearly lacked knowledge about HBV and HPV infection prevention and had difficulty understanding and educating their daughters about health behavior, especially on sex-related topics. The findings showed that histo-sociocultural factors are integrated with the individual factor, and these factors influenced the HBV and HPV knowledge and perspective of Khmer mothers' parenting. CONCLUSIONS: The study suggests that situation-specific conceptual and methodological approaches that take into account the uniqueness of the sociocultural context of CAs is a novel method for identifying factors that are significant in shaping the perception of Khmer mothers' health education related to HBV and HPV prevention among their daughters. The communication between mother and daughter about sex and the risk involved in contracting HBV and HPV has been limited, partly because it is seen as a "taboo subject" and partly because mothers think that schools educate their children regarding sexuality and health. PMID- 26160248 TI - Exogenous and endogenous determinants of vitamin K status in cystic fibrosis. AB - Cystic fibrosis (CF) patients are at high risk for vitamin K deficiency. The effects of vitamin K supplementation are very ambiguous. Therefore, we aimed to define the determinants of vitamin K deficiency in a large cohort of supplemented - 146 (86.9%) and non-supplemented - 22 (13.1%) CF patients. Vitamin K status was assessed using prothrombin inducted by vitamin K absence (PIVKA-II) and undercarboxylated osteocalcin (u-OC). The pathological PIVKA-II concentration (>= 2 ng/ml) and abnormal percentage of osteocalcin (>= 20%) were found in 72 (42.8%) and 60 (35.7%) subjects, respectively. We found that liver involvement, diabetes, and glucocorticoid therapy were potential risk factors for vitamin K deficiency. Pathological concentrations of PIVKA-II occurred more frequently in patients with pancreatic insufficiency and those who have two severe mutations in both alleles of the CFTR gene. Pathological percentage of u-OC was found more frequently in adult CF patients and those not receiving vitamin K. However, it seems that there are no good predictive factors of vitamin K deficiency in CF patients in everyday clinical care. Early vitamin K supplementation in CF patients seems to be warranted. It is impossible to clearly determine the supplementation dose. Therefore, constant monitoring of vitamin K status seems to be justified. PMID- 26160249 TI - TFAP2C expression in breast cancer: correlation with overall survival beyond 10 years of initial diagnosis. AB - Recurrence and death in a significant number of patients with ERalpha-positive breast cancer occurs 10-20 years after diagnosis. Prognostic markers for late events have been more elusive. TFAP2C (AP2gamma) regulates the expression of ERalpha, the ERalpha pioneer factors FOXA1 and GATA3, and controls ERalpha dependent transcription. The purpose of this investigation is to determine the long-term prognostic value of TFAP2C. A tissue microarray (TMA) consisting of breast tumors from 451 patients with median follow-up time of 10.3 years was created and tested for the expression of TFAP2C by immunohistochemistry. Wilcoxon Rank-Sum and Kruskal-Wallis tests were used to determine if TFAP2C H-scores correlate with other tumor markers. Cox proportional hazards regression models were used to determine whether TFAP2C H-scores and other tumor markers were related to overall and disease-free survival in univariate and multivariable models. TFPAC2 overexpression did not impact overall survival during the first 10 years after diagnosis, but was associated with a shorter survival after 10 years (HR 3.40, 95 % CI 1.58, 7.30; p value = 0.002). This late divergence persisted in ER-positive (HR 2.86, 95 % CI 1.29, 6.36; p value = 0.01) and endocrine therapy positive subgroups (HR 4.19, 95 % CI 1.72, 10.23; p value = 0.002). For the ER+ and endocrine therapy subgroup, the HR was 3.82 (95 % CI 1.53, 9.50; p value = 0.004). TFAP2C H-scores were not correlated with other tumor markers or related to disease-free survival. In this hypothesis-generating study, we show that higher TFAP2C scores correlate with poor overall survival after 10 years of diagnosis in ERalpha-positive and endocrine therapy-treated subgroups. PMID- 26160250 TI - A phase III randomized multicenter trial evaluating cognition in post-menopausal breast cancer patients receiving adjuvant hormonotherapy. AB - Cognitive impairment, especially verbal episodic memory and executive function impairments, has been considered to be a possible adverse effect of aromatase inhibitors (AI). This phase III open-label study compared the impact of tamoxifen and AI on verbal episodic memory (Rey auditory verbal learning test-RAVLT) and other cognitive functions (visual memory, psychomotor speed, and executive functions) after 6 and 12 months of treatment in breast cancer patients undergoing adjuvant hormonotherapy. Menopausal chemo-naive patients with resectable breast cancer were randomly assigned (1:1) at the end of the radiotherapy to receive tamoxifen or AI. Neuropsychological assessments, self reported quality of life, and depression assessments were performed at baseline, before any hormonal treatment, and at 6 and 12 months. Mixed design analysis models of variance was used to compare the evolution of the scores between the groups during follow-up. A total of 74 evaluable patients were enrolled (Tamoxifen arm, n = 37; AI arm, n = 37; letrozole n = 18; anastrozole n = 16; exemestane n = 3). The median age at inclusion was 61 years (range, minimum 49 maximum 69). The patient and breast cancer characteristics were well balanced between arms. After 6 months, no significant differential effect of AI or tamoxifen was observed on the RAVLT. Moreover, considering the other cognitive measures and the quality of life questionnaires, there were also no differences between the groups during the 1-year follow-up. In this study, AI has not demonstrated worse adverse effects on cognitive functions than tamoxifen during a 1-year follow-up. PMID- 26160251 TI - Episodic memory and executive function impairments in non-demented older adults: which are the respective and combined effects on gait performances? AB - Gait control depends in part on cognition. This study aims to examine the separate and combined effects of episodic memory and executive function impairments on the mean value and the coefficient of variation (CoV) of stride time among non-demented older community dwellers. Based on a cross-sectional design, 1458 older community dwellers without dementia (70.6 +/- 4.9 years; 49.2 % female) were recruited and separated into cognitively healthy individuals (CHI) and individuals with cognitive impairment. A score <=5/6 on the Short Mini-Mental State Examination defined episodic memory impairment. Impaired executive function was defined by errors on the clock-drawing test. Mean value and CoV of stride time were measured by the GAITRite(r) system. A total of 517 participants (35.5 %) had cognitive impairment in at least one cognitive domain. Participants with memory impairment (P = 0.006) and those with combined cognitive impairments (P < 0.001) had greater (i.e., worse gait performance) mean value of stride time (P = 0.006) compared to CHI. Participants with combined cognitive impairment had a greater CoV of stride time (i.e., worse gait performance) compared to CHI (P = 0.004) and to those with separate memory impairment (P = 0.037). Among participants with combined cognitive impairments, mean value and CoV of stride time had the highest effect size (respectively, effect size = 0.49 [95 % confidence interval (CI) 0.27;0.71] and effect size = 0.40 [95 %CI 0.18;0.62]). Participants with episodic memory or executive impairments had a greater mean value and CoV of stride time compared to those with no cognitive impairment. Combined episodic memory and executive impairments exceeded the sum of separate impairments on gait performances, suggesting a complex interplay going beyond a simple additive effect. PMID- 26160252 TI - Disaccharidase Deficiencies in Children With Chronic Abdominal Pain. AB - OBJECTIVES: Carbohydrate intolerance or malabsorption has been suggested as a cause of chronic abdominal pain (CAP) in a subset of patients. We aimed to evaluate disaccharidase deficiencies in children with functional CAP and to correlate deficiencies with clinical features. METHOD: Patients presenting to the gastroenterology clinic at Children's Hospital of Wisconsin with abdominal pain prospectively completed a detailed demographic, history, and symptom questionnaire. The CAP cohort included those with at least 1 month of symptoms. Data on disaccharidase activity and histology of endoscopic biopsies were collected retrospectively. Only patients with normal histology were included in the study. The association between groups with low disaccharidases and clinical features was examined. RESULTS: A total of 203 pediatric patients with CAP were included. The mean (SD) age was 11.5 (3.1) years, and 32.5% were male. The percentages of abnormally low disaccharidase levels using the standard laboratory cutoffs were lactase, 37%; sucrase, 21%; glucoamylase, 25%; and palatinase, 8%. Thirty-nine percent of the patients with low lactase also had low sucrase, and 67% of the patients with low sucrase had low lactase. There was no significant difference in the activities of any of the disaccharidases or sucrase/lactase ratio in relation to age. Also, no association was found between stool consistency, stool frequency, or location of pain and low disaccharidase activity. CONCLUSIONS: A large proportion of patients with CAP have deficiencies in disaccharidases. Bowel frequency, vomiting, or location of pain was no different between groups, suggesting that these clinical features cannot be used to predict disaccharidase deficiencies. PMID- 26160253 TI - How Close Are We to Achieving Energy and Nutrient Goals for Very Low Birth Weight Infants in the First Week? AB - BACKGROUND: Emerging evidence suggests intakes of protein and energy as early as the first week of life in preterm very low birth weight (VLBW) infants are associated with improved neurodevelopment. In response, many neonatal intensive care units (NICUs) have launched new, more aggressive early feeding guidelines. The aim of this study was to evaluate enteral and parenteral energy and macronutrient intakes during the first postnatal week in VLBW infants admitted to NICUs that have introduced more aggressive early feeding guidelines. MATERIALS AND METHODS: Estimated energy and macronutrient intakes were prospectively collected from VLBW infants fed exclusively mother's own milk and/or parenteral nutrition and compared with expert recommendations. Days to reach full enteral feeds (150 mL/kg/d) and discharge anthropometrics were examined. RESULTS: By days 6 and 7, median protein and lipid intakes, respectively, reached recommended values (3.5 and 3.0 g/kg/d). However, by day 8, many infants remained below recommended intakes for protein (34%), lipid (34%), carbohydrate (68%), and energy (71%). Late-onset sepsis was associated with a decreased likelihood of reaching full enteral feeds on any given day (hazard ratio, 0.2; 95% confidence interval, 0.1-0.5; P <= .0009). There was no significant relationship between week 1 nutrient intakes and anthropometrics at discharge. CONCLUSION: Despite the introduction of more aggressive early feeding guidelines and improved energy and nutrient intakes compared with literature values, many VLBW infants remain below recommended nutrition goals in the first week. PMID- 26160254 TI - Comprehensive Safety Monitoring of 12-Month Daily 7000-IU Vitamin D3 Supplementation in Human Immunodeficiency Virus-Infected Children and Young Adults. AB - BACKGROUND: There is uncertainty whether long-term daily dosing with vitamin D3 (cholecalciferol) supplementation (vitD3) above the 4000-IU/d dietary reference intake upper tolerable limit in children and adults is safe. As part of a randomized placebo-controlled trial, we determined if supplementation with 7000 IU/d vitD3 for 12 months in human immunodeficiency virus (HIV)-Infected subjects was safe and/or associated with metabolic outcomes. MATERIAL AND METHODS: A total of 58 HIV-infected subjects-aged 9-24.9 years and stratified by mode of HIV acquisition (perinatal or behavioral)-were recruited, randomized to 7000-IU/d vitD3 or placebo, and followed at 3, 6, and 12 months with physical examinations, blood and urine sampling for measures of 25(OH)D (serum 25-hydroxyvitamin D), metabolic status, safety measures, and HIV immune status. Safety was defined by a low incidence (<5%) of the study-defined serious adverse events-that is, elevated serum calcium plus 25(OH)D >160 ng/mL-and no changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. RESULTS: Randomization groups did not differ in demographic characteristics, vitamin D status, or HIV disease status at baseline. Over the 12 months, serum 25(OH)D increased with supplementation. No subject experienced a serious adverse safety event; none had 25(OH)D >80 ng/mL at any time. There were no clinically significant changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. CONCLUSIONS: Safety of daily 7000-IU vitD3 supplementation in children and young adults with HIV was comprehensively monitored over 12 months. High-dose daily vitD3 supplementation was efficacious in improving vitamin D status, and there were no safety events. PMID- 26160255 TI - The West African Ebola outbreak: finishing the job, preparing for future. AB - As the West African Ebola Outbreak moves towards the final stages, we must consider the importance of remaining work and take heed of lessons learned in preparation for future outbreaks. Several issues pertinent to preparedness must be considered, including the remaining animal reservoir and potential for sexual transmission. Testing must be accessible and contact tracing robust to trace the last patient. Improved infection control procedures alongside education and training require guaranteed supply chains and ongoing funding. Effort must be sustained to prevent an even greater catastrophe than the one inflicted on West Africa today. PMID- 26160257 TI - Self-assembly and morphological transitions of random amphiphilic poly(beta-D glucose-co-1-octyl) phosphazenes. AB - The amphiphilic random copolymer poly(beta-d-glucose-co-1-octyl)phosphazene (PGOP) can undergo continuous morphological transitions in DMF-water mixed solvents. In this study, the ratio of glucose moieties to octyl moieties was controlled via a two-step thiol-ene reaction. As a result, polyphosphazenes with glycosyl functionalization degrees of 58.1% (PGOP-1), 74.1% (PGOP-2) and 87.0% (PGOP-3) were obtained. These amphiphilic polyphosphazenes self-assemble in both water and water-DMF mixtures. Several self-assembled morphologies including spheres, rods and vesicles were formed though careful control of the water content (WC) in the DMF solvent as well as of the hydrophilicity or hydrophobicity of the copolymers. We also found that an increase in the hydrophobic proportion led to faster morphological transitions at a constant WC. The thermodynamics of micellization were also studied by Isothermal Titration Calorimetry (ITC), and the strong hydrophobic interactions in PGOP-1 were demonstrated by their highly exothermic nature. These self-assemblies have potential applications in biosensing, lectin adsorption and drug loading with controlled release. PMID- 26160256 TI - Spatial patterns and determinants of malaria infection during pregnancy in Zambia. AB - BACKGROUND: Malaria in pregnancy (MiP) is a major concern in Zambia. Here we aim to determine the burden and risk factors of MiP. METHODS: Monthly reported district-level malaria cases among pregnant women (count data) from January 2009 to December 2014 were obtained from the Zambian District Health Information System. Negative binomial regression model was used to investigate the associations between vector control tools, coverage of health care facilities, transportation networks and population density. Data on MiP treatment were obtained from the 2012 Zambian Malaria Indicator Survey. Yearly clusters of MiP were investigated using spatial statistics in ArcGIS v 10.1. RESULTS: The results indicated that MiP decreased in Zambia between 2010 and 2013. MiP was observed throughout the year, but showed a strong seasonal pattern. Persistent hotspots of MiP were reported in the southeast and northeast regions of Zambia, with districts that had better access to rail road and presence of water bodies associated with decreased prevalence of MiP. Better indoor residual spraying and long-lasting insecticide-treated nets coverage was demonstrated to be protective against MiP. CONCLUSIONS: Mapping the distribution of MiP to track the future requirements for scaling up essential disease-prevention efforts in stable hotspots can help the Zambian National Malaria Control Center to further develop strategies to reduce malaria prevalence in this vulnerable sub-population. PMID- 26160258 TI - Lower Respiratory Tract Adenoid Cystic Carcinoma: Its Management in the Past Decades. AB - AIMS: Adenoid cystic carcinoma of the lower respiratory tract is a rare indolent neoplasm with prolonged survival, propensity for recurrences and metastasis years after initial therapy. We aim to study a 1,700-bed single tertiary academic hospital's long-term experience with ACC of the lower respiratory tract from the larynx to the lungs and review published literature on this subject. MATERIALS AND METHODS: We analysed the clinicopathology, treatment options and outcome in 33 patients and reviewed the published literature over the last five decades. RESULTS: The tumour has no gender predilection, a peak incidence in the fifth decade and is not related to smoking. Insidious symptoms are often treated as benign obstructive airway disease and infection; negative signs and normal chest X-rays delayed diagnosis. The tumour was distributed most commonly in the trachea followed by main bronchi, lobar bronchi and larynx. About 22% of patients required emergent bronchoscopic intervention to secure airway patency before definitive therapy with surgery or/and radiotherapy. A high proportion of resected specimens had positive margins. Overall survival and disease-free survival rates at 5 years were 81 and 62%, respectively, and at 10 years 70 and 54%, respectively. Prolonged good palliation was achieved for patients with unresectable lesions with radiation and wide armamentarium of endoscopic therapy. CONCLUSIONS: In time, many patients eventually succumb to this disease. However, advances in medical skill and technology have prolonged survival while maintaining a good quality of life. Adenoid cystic carcinoma of the respiratory tract is a chronic life-long disease that may require interval intensive therapy. The challenge is to find the best therapeutic regimen aiming for a 'true' cure. Further study on the mutational landscape of adenoid cystic carcinoma may provide potential avenues for novel treatments to address a chemoresistant cancer. PMID- 26160259 TI - Laparoscopic Management of Sclerosing Stromal Tumors of the Ovary Combined with Ectopic Pregnancy. AB - Like other stromal-derived gynecological tumors, a sclerosing stromal tumor of the ovary (SSTO) is a rare benign tumor that is difficult to distinguish from a malignant ovarian tumor in clinical practice. An SSTO is routinely treated with laparotomy. Here, we present two extremely rare cases of SSTO with contralateral and ipsilateral tubal pregnancies, in which laparoscopic surgery was performed to remove the tumors. After surgery, one patient (case 1) became pregnant twice within 29 months, and the other patient (case 2) did not become pregnant within 6 months postoperatively. These two cases suggest that laparoscopic management is not only useful in treating SSTO and complicating diseases, but it may also help to reduce unnecessary surgical injury to the ovary. PMID- 26160260 TI - Epigenetic Dysregulation in the Prefrontal Cortex of Suicide Completers. AB - The epigenome is thought to mediate between genes and the environment, particularly in response to adverse life experiences. Similar to other psychiatric diseases, the suicide liability of an individual appears to be influenced by many genetic factors of small effect size as well as by environmental stressors. To identify epigenetic marks associated with suicide, which is considered the endpoint of complex gene-environment interactions, we compared the cortex DNA methylation patterns of 6 suicide completers versus 6 non psychiatric sudden-death controls, using Illumina 450K methylation arrays. Consistent with a multifactorial disease model, we found DNA methylation changes in a large number of genes, but no changes with large effects reaching genome wide significance. Global methylation of all analyzed CpG sites was significantly (0.25 percentage point) lower in suicide than in control brains, whereas the vast majority (97%) of the top 1,000 differentially methylated regions (DMRs) were higher methylated (0.6 percentage point) in suicide brains. Annotation analysis of the top 1,000 DMRs revealed an enrichment of differentially methylated promoters in functional categories associated with transcription and expression in the brain. In addition, we performed a comprehensive literature research to identify suicide genes that have been replicated in independent genetic association, brain methylation and/or expression studies. Although, in general, there was no significant overlap between different published data sets or between our top 1,000 DMRs and published data sets, our methylation screen strengthens a number of candidate genes (APLP2, BDNF, HTR1A, NUAK1, PHACTR3, MSMP, SLC6A4, SYN2, and SYNE2) and supports a role for epigenetics in the pathophysiology of suicide. PMID- 26160261 TI - Simultaneously measured inter-arm and inter-leg systolic blood pressure differences and cardiovascular risk stratification: a systemic review and meta analysis. AB - Association of inter-arm systolic blood pressure difference (IASBPD) with cardiovascular (CV) morbidity and mortality remains controversial. We aimed to thoroughly examine all available evidence on inter-limb blood pressure (BP) difference and its association with CV risk and outcomes. We searched PubMed, EMBASE, CINAHL, Cochrane library, and Ovid for studies reporting bilateral simultaneous BP measurements in arms or legs and risk of peripheral arterial disease (PAD), coronary artery disease, cerebrovascular disease, subclavian stenosis, or mortality. Random-effect meta-analysis was performed to compare effect estimates. Twenty-seven studies met inclusion criteria, but only 17 studies (18 cohorts) were suitable for analysis. IASBPD of 10 mmHg or more was associated with PAD (risk ratios, 2.22; 1.41-3.5; P = .0006; sensitivity 16.6%; 6.7-35.4; specificity 91.9%; 83.1-96.3; 8 cohorts; 4774 subjects), left ventricular mass index (standardized mean difference 0.21; 0.03-0.39; P = .02; 2 cohort; 1604 subjects), and brachial-ankle pulse wave velocity (PWV) (one cohort). Association of PAD remained significant at cutoff of 15 mmHg (risk ratios, 1.91; 1.28-2.84; P = .001; 5 cohorts; 1914 subjects). We could not find statistically significant direct association of coronary artery disease, cerebrovascular disease, CV, and all-cause mortality in subjects with IASBPD of 10 mmHg or more, 15 mmHg or more, and inter-leg systolic BP difference of 15 mmHg or more. Inter-leg BP difference of 15 mmHg or more was strong predictor of PAD (P = .0001) and brachial-ankle PWV (P = .0001). Two invasive studies showed association of IASBPD and subclavian stenosis (estimates could not be combined). In conclusion, inter-arm and leg BP differences are strong predictors of PAD. IASBPD may be associated with subclavian stenosis, high left ventricular mass effect, and higher brachial-ankle PWVs. Inter-leg BP difference may also be associated with high left ventricular mass effect and higher brachial-ankle PWVs. Presence of inter-limb BP difference may indicate higher global CV risk. PMID- 26160263 TI - Long-term habitual physical activity is associated with lower distractibility in a Stroop interference task in aging: Behavioral and ERP evidence. AB - Aging is associated with compromised executive control functions. Several lines of evidence point to beneficial effects of physical activity on cognition which indicate that regular physical activity may counteract the age-related decline of some executive functions. Here, we investigate the effects of lifelong physical activity (about 50 years) on interference processing in two matched groups of 20 physically high active and 20 low active healthy older men using event-related potentials (ERPs). In a low interference block of the Stroop task, participants had to indicate the meaning of color-words, while color was either compatible or incompatible with the meaning. In the high interference block, participants were asked to respond according to the ink color of the word and to ignore its meaning. Physically active seniors showed faster reaction times, lower individual variability in reaction times, and higher accuracy compared to low active seniors, particularly in the high interference block. This result was confirmed in the classic paper-and-pencil version of the Stroop task showing higher interference score in the low active than high active individuals. ERPs revealed a shorter latency of the P2 and generally more negative amplitudes of the fronto central N2 and N450 components in the high active group compared to the low active group. The amount of interference was negatively correlated with objectively measured fitness and self-reported physical activity. The positive effect of physical fitness on interference processing in the behavioral data was related to N2 and N450 amplitudes. Taken together, this suggests that seniors reporting long-term physical activity may exhibit generally enhanced activity in the frontal cortex which enables more efficient interference resolution in the Stroop task. PMID- 26160262 TI - Oxidative stress, oxidative balance score, and hypertension among a racially diverse population. AB - Hypertension is a risk factor for several vascular diseases. Evidence suggests that oxidative stress (OS) plays a significant role in its pathophysiology. Human studies have shown inconsistent results, varying based on the OS biomarker and study population. In a racially diverse population, examine the association between: (1) blood pressure or hypertension and four markers of OS and (2) blood pressure or hypertension and oxidative balance score (OBS). Using data (n = 317) from the cross-sectional study on race, stress, and hypertension, an OBS was constructed from various measures of pro-oxidant and antioxidant exposures. OS was assessed by four biomarkers: fluorescence oxidative products, F2 isoprostanes, mitochondrial DNA copy number, and gamma tocopherol. Multivariate linear and logistic regression analyses were used to estimate the associations of interest. None of the adjusted associations between hypertension and OS markers was statistically significant. OBS was inversely associated with hypertension after adjusting for study covariates. Persons with higher OBS have lower odds of having hypertension; however, the evidence on the relationship between OS markers and blood pressure remains unconvincing. PMID- 26160264 TI - Implicit agreeing/disagreeing intention while reading self-relevant sentences: A human fMRI study. AB - The true intentions of humans are sometimes difficult to ascertain exclusively from explicit expressions, such as speech, gestures, or facial expressions. In this experiment, functional magnetic resonance imaging (fMRI) was used to investigate implicit intentions that were generated while a subject was reading self-relevant sentences. Short sentences, which were presented visually, consisted of self-relevant statements and a substantive verb, which indicated sentence polarity as either affirmative or negative. Each sentence was divided into the contents and the sentence ending, and the subjects were asked to respond with either agreement or disagreement after the complete sentence was presented. The overall group analysis suggested that the intention of the sentence response was found even before the reading of the complete sentences. Increased neural activation was found in the left medial prefrontal cortex (MPFC) during feelings of agreement compared to feelings of disagreement during self-relevant decision making. In addition, according to the sentence ending, the decision of a response activated the frontopolar cortex (FPC) in the switching condition. These findings indicated that the implicit intentions of responses to the given statements were internally generated before an explicit response occurred, and, hence, intentions can be used to predict a subject's future answer. PMID- 26160267 TI - Click made porphyrin-corrole dyad: a system for photo-induced charge separation. AB - The preparation of the first porphyrin-corrole dyad through click chemistry is described. The absorption, the emission and the electrochemical properties were investigated and suggested an efficient excited state interaction between the porphyrin and the corrole unit. Theoretical calculations were performed and proved that the dyad can potentially act as a molecular system for solar energy conversion schemes. PMID- 26160266 TI - Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement. AB - The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 +/ 0.76 pg/ml) than in healthy individuals (1.89 +/- 0.69 pg/ml; p < 0.0001). Patients with lung fibrosis had higher IL-35 levels than those without fibrosis (7.75 +/- 1.36 and 3.08 +/- 0.70 pg/ml, respectively, p = 0.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc. PMID- 26160265 TI - CRDC: a Chinese rheumatology research platform. AB - This review introduces the history of development, organizational structure, funding resources, data collection, and quality control of the Chinese Rheumatism Data Center (CRDC) and summarizes the collection of data. In 2009, Peking Union Medical College Hospital (PUMCH), together with several rheumatism centers, established the Chinese Systemic Lupus Erythematosus (SLE) Treatment and Research Group (CSTAR) to collect data on Chinese patients for the study of SLE disease characteristics. In 2011, CSTAR was extended with the formation of the CRDC at PUMCH with direction from the National Health and Family Planning Commission of the PRC. The CRDC currently includes 300 registration sites and 50 regional sites that have successively begun to collect data on 12 rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, dermatomyositis, Takayasu arteritis, IgG4 related diseases, ANCA-associated vasculitis, gout, polyarteritis nodosa, unclassified systemic vasculitis, and Behcet disease. To date, 17,224 patients have been enrolled in the CRDC. Based on the SLE patients registered in the CRDC, papers investigating basic demographic characteristics and first symptom in Chinese SLE patients, risk factors of pulmonary hypertension, correlations between autoantibodies and clinical manifestations, and factors related to fetal loss have been published. The CRDC is a national registry that provides real-life data to improve clinical decision-making. At the same time, without additional work for the clinician, the CRDC is a powerful research database. The CRDC database provides sufficient information for Chinese clinical studies on rheumatology. Moreover, a mobile device application ensures convenient and efficient data collection without compromising data quality, thereby providing strong evidence-based data for the diagnosis and treatment of Chinese rheumatic patients. PMID- 26160268 TI - Annular Lichenoid Dermatitis of Youth: Report of Six New Cases with Review of the Literature. AB - BACKGROUND: Annular lichenoid dermatitis of youth (ALDY) is an uncommon disease clinically reminiscent of morphea, annular erythema or mycosis fungoides. OBJECTIVE: To describe the histological and clinical features of a small series of patients with ALDY and to review the literature. PATIENTS: We describe the clinical and histological features of six patients (age range 7-79 years) with asymptomatic erythematous macules and patches with a red-brownish border and central hypopigmentation, mostly distributed on the groin and flanks. Histologically, all cases showed lichenoid dermatitis limited to the tips of rete ridges, with many intraepidermal CD8+ and some CD4+ T cells. T cell receptor rearrangement was absent in all cases. A total of 44 patients with a consistent clinical and histological picture have been described. The disease is sensitive to topical and/or systemic corticosteroids. CONCLUSIONS: ALDY is a unique lichenoid dermatitis for whose diagnosis a clinical-pathological correlation is essential. The disease typically affects young patients, more rarely adults and elderly. PMID- 26160269 TI - The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology. AB - BACKGROUND/AIMS: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on the ARDS etiology and the dose. METHODS: C57/BL6 mice were divided to be pre-treated with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage. Thirty-minutes after pre treatment, mice were subdivided into control (C) or ARDS groups. ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h. RESULTS: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-beta in ARDSp. The higher dose of dasatinib caused no changes in lung mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6, vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp. In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing TLR4. Conclusion: Dasatinib may have therapeutic potential in ARDS independent of etiology, but careful dose monitoring is required. PMID- 26160270 TI - Porphyrin-loaded liposomes and graphene oxide used for the membrane pore-forming protein assay and inhibitor screening. AB - The interaction of planar aromatic molecules with the graphene oxide (GO) sheets is often marked by the fluorescence quenching of the former. Here, the alpha,beta,gamma,delta-tetrakis[4-(trimethylammoniumyl)phenyl]porphyrin (TAPP) molecules and the GO, corresponding to the energy donor and the acceptor respectively, are initially separated by encapsulating the TAPP molecules within the liposomes, to obstruct the formation of the self-assembled energy transfer based quenching system. Upon disruption of the liposome membranes by the PLA2 or the alpha-toxin, the encapsulated TAPP molecules are released and subsequently result in significant fluorescence changes. Thus, a platform based on the fluorescence signal for monitoring the activity of the membrane pore-forming protein with advantages of high sensitivity and commonality was established. Using this strategy, we can detect the PLA2 and the alpha-toxin concentrations as low as 200 pM and 9.0 nM, respectively. Furthermore, by taking chlorpromazine and baicalin as the examples, we use the assay to evaluate the prohibition effects on the PLA2 and the alpha-toxin, and the IC50 values of chlorpromazine toward the PLA2 (9.6 nM) and that of baicalin toward the alpha-toxin (289.2 nM) were found to be 12.0 +/- 0.62 MUM and 26.9 +/- 2.6 MUM, respectively. PMID- 26160271 TI - Temporal control of behaviour in children with differential reinforcement of low rates schedule: the role of age, language and cognitive functioning on temporal regulation. AB - Research on temporal regulation in children has been prolific until early 1990s and has received a very limited attention since then. However, the studies focussed mainly on very short durations, and many questions raised at that time remain unanswered (Clement et al., 2007). The scope of this study was to evaluate temporal control in children with differential reinforcement of low-rates (DRL) schedule. Objectives were (a) to evaluate the performance in DRL with two distinct durations; (b) to evaluate the relationship between performance, IQ and language; and (c) to observe children's response patterns across the sessions. Eleven children aged from 2.6 to 7 years old were exposed to a DRL 5s and a DRL 20s schedule. No significant correlation was observed between language, IQ and the performance in DRL. In DRL 5s, seven children adjusted their responses and six in DRL 20s. Age was positively correlated to performance in DRL 5s, while the response patterns in DRL 20s were hardly predictable. In both conditions, children aged from 4.6 years old showed a lower proportion of bursting responses, a lower rate of response, a larger proportion of reinforced responses and a higher optimisation coefficient. PMID- 26160272 TI - The Expression and Significance of NLRP3 Inflammasome in Patients with Primary Glomerular Diseases. AB - BACKGROUND/AIMS: Primary glomerulonephritis (PGN) is the most common reason inducing end stage renal disease in China, however, its pathogenesis remains unclear. The present study was designed to test the hypothesis that the formation and activation of NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasomes is an important initiating mechanism resulting in PGN. METHODS: Serum samples and frozen sections were collected from 38 cases with PGN, and renal tissues were obtained from 22 of them. NLRP3 inflammasomes were detected by RT-PCR and immunofluoresence methods. The relationship between NLRP3 and clinical/pathologic indexes was analyzed. RESULTS: RT-PCR analyses demonstrated that the mRNA levels of NLRP3 and caspase-1 genes were elevated significantly in renal tissues of PGN patients compared to those from normal pericarcinoma tissues. Moreover, the increased level of NLRP3 mRNA was correlative with a decrease in nephrin mRNA level and an increase in desmin mRNA level, which indicates that NLRP3 participates in podocyte injury in PGN patients. Immunofluorescence analysis also showed the protein expressions of NLRP3 and caspase-1 were increased in the glomeruli of PGN patients. Neverthless, there was no obvious regularity was presented in further subgroup analysis according to pathological types. In addition, increased NLRP3 was associated with the deterioration of renal function and glomerulosclerosis. IL-1beta, a product of NLRP3 inflammasome activation, had a significant correlation with proteinuria. CONCLUSIONS: The formation and activation of NLRP3 inflammasomes in podocytes has been importantly implicated in the development of PGN-associated glomerular injury. PMID- 26160273 TI - Biomechanical modelling of impact-related fracture characteristics and injury patterns of the cervical spine associated with riding accidents. AB - BACKGROUND: Horse-related injuries are manifold and can involve the upper and lower limbs, the trunk, spine or head. Cervical spine injuries are not among the most common injuries. However, they can be fatal and often result in neurological symptoms. This study investigated the influence of the posture of the cervical spine on the ultimate strength and the pattern of vertebrae failure with the aim to provide some guidance for protective clothing design. METHODS: Eighteen human cervical spines, each divided into two specimens (three vertebrae each), were subjected to a simulator test designed to mimic a spinal trauma in different postures of the specimen (neutral, flexion, extension). The stress-to-failure, the deformation at the time of fracture and the fracture patterns assessed based on CT scans were analysed. FINDINGS: Stress-to-failure of the superior specimens was lower for the flexion group compared to the others (P=0.027). The superior specimens demonstrated higher stress-to-failure in comparison to the inferior specimens (P<0.001). Compression in a neutral or flexed position generated mild or moderate fracture patterns. On the contrary, the placement of the spine in extension resulted in severe fractures mostly associated with narrowing of the spinal canal. INTERPRETATION: The results imply that a neutral cervical spine position during an impaction can be beneficial. In this position, the failure loads are high, and even if a vertebral fracture occurs, the generated injury patterns are expected to be mild or moderate. PMID- 26160274 TI - Abnormal degree centrality in neurologically asymptomatic patients with end-stage renal disease: A resting-state fMRI study. AB - OBJECTIVE: End-stage renal disease (ESRD), characterized by multi-organ dysfunction, has been shown to co-occur with abnormal brain function. Previous resting-state fMRI studies suggested that regional brain spontaneous activity and functional connectivity within the default mode network are abnormal in ESRD patients. The current study aimed to depict intrinsic dysconnectivity pattern of whole-brain functional networks in voxel level in neurologically asymptomatic patients with ESRD. METHODS: fMRI datasets were acquired from 22 ESRD patients (without clinical neurological disease) and 29 healthy control (HC) subjects. We investigated the degree centrality for a given element in a network to reveal the changes of functional connectivity throughout the huge human functional network. In the brain regions showing a difference between the HC and ESRD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the accuracy, sensitivity and specificity of our results. RESULTS: ESRD patients showed decreased functional connectivity in the left inferior parietal and left precuneus within the brain network; both regions are important components of the default-mode network (DMN). In contrast, patients showed increased connectivity in depression-related regions including bilateral inferior frontal gyrus and right superior temporal gyrus. These regions showed an acceptable accuracy (0.68 0.75), sensitivity (0.64-0.70) and high specificity (0.82-0.96) in distinguishing between the two groups. CONCLUSIONS: Our findings reveal abnormal intrinsic dysconnectivity pattern of whole-brain functional networks in ESRD patients. SIGNIFICANCE: Our results could lead to a better understanding of the intrinsic dysconnectivity patterns of default-mode network-related regions in ESRD patients from the whole brain network perspective. PMID- 26160275 TI - Markers for upper limb dysfunction in Amyotrophic Lateral Sclerosis using analysis of typing activity. AB - OBJECTIVE: Assistive devices based on keyboard access support communication and control tools for patients with Amyotrophic Lateral Sclerosis (ALS). The aim of this work was to explore movement activity in the use of keyboards and identify markers for upper limb (UL) dysfunction. METHODS: We present a longitudinal study including 19 ALS patients, followed for 2-20 months. Typing activity was recorded with an accelerometer placed on the posterior part of patients' index finger. Participants performed the same 10-word typing task (2-6 assessments). Time and acceleration during keystroke were the main outcomes of this study. Patients were compared with 20 healthy subjects and 6 patients with other neuromuscular disorders. RESULTS: During disease progression, mean time in holding down a key increased and was longer than in control subjects. Acceleration at key press and key release decreased with progression of UL dysfunction. Delay between tapping and pressing down each key increased with UL dysfunction. CONCLUSIONS: Delay in pressing and releasing keys are markers of UL dysfunction in ALS. The decrease in the acceleration of movements related to keystroke can contribute to monitor disease progression. SIGNIFICANCE: Typing activity can be explored to access remotely and continuously to ALS progression by patients who use assistive communication devices. PMID- 26160276 TI - Epidemiology of echinococcosis in Kazakhstan: an update. AB - Kazakhstan is highly endemic for echinococcosis. Both Echinococcus granulosus and E. multilocularis are widely distributed in the country. Official records of human cystic echinococcosis over the past 5-10 years suggest a stable incidence of approximately 800-1000 cases per year, which is 5 cases per 100,000 per year. This followed a rapid increase in the incidence following the dissolution of the Soviet Union. Between 2007 and 2013, 5949 cases were reported in the national surveillance data. The prevalence in sheep, based on slaughterhouse studies, suggests that between 30 and 50% of sheep are infected with hydatid cysts, while cattle have a prevalence of approximately 7%. Rural dogs have a high prevalence of infection of between 5 and 10%, with shepherd dogs having prevalences of over 20%. G1 and G6/7 strains of E. granulosus have been isolated from dogs in Kazakhstan. Wolves are also infected, with one prevalence estimate of approximately 20%. The incidence of human alveolar echinococcosis is less clear, although estimates from Kazakhstani expatriates living in Germany and the hospital records of a single referral centre in Almaty suggest 34 or 130 cases per year (or an annual incidence of 0.20 or 0.76 cases per 100,000), respectively, could be occurring in Kazakhstan. Studies suggest that in some rural dog populations the prevalence may be about 5%. The parasite is widely distributed in foxes and small mammals through much of Kazakhstan. PMID- 26160277 TI - An evaluation of a Singing for the Brain pilot with people with a learning disability and memory problems or a dementia. AB - This paper presents the findings from a pilot project introducing Singing for the Brain into care centres with people with a learning disability and a form of dementia or memory problem. Through participant observations, patient and staff feedback, there was strong support for the use of Singing for the Brain with this client group, with participants reporting high levels of enjoyment and engagement in the sessions. The potential for these sessions to support communication, memory, social engagement and choice was reported by staff and participants. Whilst anecdotal reports also suggested the sessions had a positive impact on elevating mood over a sustained period of time. The pilot sessions are discussed in reference to the regular sessions run for people with dementia and comparisons drawn across the two approaches. Further evidence is required to understand the potential impact on participant's well-being from attending these sessions. PMID- 26160278 TI - T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats. AB - Myocardial infarction leads to a reduction in nitric oxide (NO) bioavailability and an increase in reactive oxygen species (ROS) levels. This scenario has been shown to be detrimental to the heart. Recent studies have shown that thyroid hormone (TH) administration presents positive effects after ischaemic injury. Based on this, the aim of this study was to evaluate the effect of TH on NO bioavailability as well as on endothelial nitric oxide synthase (eNOS) expression after myocardial infarction. Male Wistar rats were divided into three groups: Sham-operated (SHAM), infarcted (AMI) and infarcted + TH (AMIT). During 26 days, the AMIT group received T3 and T4 (2 and 8 ug/100 g/day, respectively) by gavage, while SHAM and AMI rats received saline. After this, the rats underwent echocardiographic analysis were sacrificed, and the left ventricle was collected for biochemical and molecular analysis. STATISTICAL ANALYSIS: one-way ANOVA with Student-Newman-Keuls post test. AMI rats presented a 38% increase in ROS levels. TH administration prevented these alterations in AMIT rats. The AMIT group presented an increase in eNOS expression, in NOS activity and in nitrite levels. TH administration also increased PGC-1alpha expression in the AMIT group. In conclusion, TH effects seem to involve a modulation of eNOS expression and an improvement in NO bioavailability in the infarcted heart. PMID- 26160279 TI - Phospholipid alterations in the brain and heart in a rat model of asphyxia induced cardiac arrest and cardiopulmonary bypass resuscitation. AB - Cardiac arrest (CA) induces whole-body ischemia, causing damage to multiple organs. Ischemic damage to the brain is mainly responsible for patient mortality. However, the molecular mechanism responsible for brain damage is not understood. Prior studies have provided evidence that degradation of membrane phospholipids plays key roles in ischemia/reperfusion injury. The aim of this study is to correlate organ damage to phospholipid alterations following 30 min asphyxia induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation using a rat model. Following 30 min CA and CPB resuscitation, rats showed no brain function, moderately compromised heart function, and died within a few hours; typical outcomes of severe CA. However, we did not find any significant change in the content or composition of phospholipids in either tissue following 30 min CA or CA followed by CPB resuscitation. We found a substantial increase in lysophosphatidylinositol in both tissues, and a small increase in lysophosphatidylethanolamine and lysophosphatidylcholine only in brain tissue following CA. CPB resuscitation significantly decreased lysophosphatidylinositol but did not alter the other lyso species. These results indicate that a decrease in phospholipids is not a cause of brain damage in CA or a characteristic of brain ischemia. However, a significant increase in lysophosphatidylcholine and lysophosphatidylethanolamine found only in the brain with more damage suggests that impaired phospholipid metabolism may be correlated with the severity of ischemia in CA. In addition, the unique response of lysophosphatidylinositol suggests that phosphatidylinositol metabolism is highly sensitive to cellular conditions altered by ischemia and resuscitation. PMID- 26160280 TI - Down-regulated miR-28-5p in human hepatocellular carcinoma correlated with tumor proliferation and migration by targeting insulin-like growth factor-1 (IGF-1). AB - Hepatocellular carcinoma (HCC) is a rapidly progressing, incurable cancer that frequently spreads to portal vein and lung. New insights are needed to identify therapeutic targets to prevent or retard HCC metastatic progression. Because microRNAs (miRNA) often act as tumor regulators, we investigated their role in preclinical models of HCC. Here we found miR-28-5p is a liver-relevant anti proliferative miRNA whose expression, functions, and mechanisms were analyzed in human hepatoma cells, HepG2 and Huh7. Interestingly, when evaluating the specific targets of miR-28-5p, we found that ectopic miR-28-5p expression down-regulates insulin-like growth factor 1 (IGF1) protein and that the expression of miR-28-5p correlates negatively with IGF1 protein in HCC cells. Luciferase report in HCC cells expressing miR-28-5p suggests that miR-28-5p reduces luciferase activity by targeting the 3'-UTR of IGF1 mRNA. Additionally, we show that the selective inhibition of either the PI3K/AKT pathway prior to miR-28-5p stimulation prevents the expression of previously described tumor suppressor miRNAs that are family and cluster specific. Together, our results defined miR-28-5p as a critical regulator of IGF1 mRNA translation function, down-regulated miR-28-5p in HCC was associated with tumor growth through PI3K/AKT pathway by targeting IGF1. miR-28 5p-IGF1-PI3K/AKT pathway may play an important role in the development of HCC. PMID- 26160281 TI - Exon array analysis reveals genetic heterogeneity in atypical femoral fractures. A pilot study. AB - Atraumatic subtrochanteric and diaphyseal (atypical) femoral fractures are a rare, but important adverse event in patients treated with potent anti-resortive agents. The mechanisms involved are unknown and particularly the association with genetic variants has not been explored. The aim of the study was to identify rare genetic variants that could be associated with the occurrence of these fractures. We performed a genome-wide analysis of up to 300,000 variants, mainly distributed in gene coding regions, in 13 patients with atypical femoral fractures and 268 control women, either healthy or with osteoporosis. Twenty one loci were more frequent in the fracture group, with a nominal p value between 1 * 10(-6) and 2.5 * 10(-3). Most patients accumulated two or more allelic variants, and consequently the number of risk variants was markedly different between patients and controls (p = 2.6 * 10(-22)). The results of this pilot study suggest that these fractures are polygenic and are associated with the accumulation of changes in the coding regions of several genes. PMID- 26160283 TI - Letter on the article "An hemorrhagic fever with renal syndrome revealing a leptospirosis". PMID- 26160282 TI - Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress. AB - The purpose of this study was to investigate the influence of non-physiological high shear stress on activation and shedding of platelet GP IIb/IIIa receptors. The healthy donor blood was exposed to three levels of high shear stresses (25, 75, 125 Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5 s), created by a specific blood shearing system. The activation and shedding of the platelet GPIIb/IIIa were analyzed using flow cytometry and enzyme-linked immunosorbent assay. In addition, platelet P-selectin expression of sheared blood, which is a marker for activated platelets, was also analyzed. The results from the present study showed that the number of activated platelets, as indicated by the surface GPIIb/IIIa activation and P-selectin expression, increased with increasing the shear stress level and exposure time. However, the mean fluorescence of GPIIb/IIIa on the platelet surface, decreased with increasing the shear stress level and exposure time. The reduction of GPIIb/IIIa on the platelet surface was further proved by the reduction of further activated platelet GPIIb/IIIa surface expression induced by ADP and the increase in GPIIb/IIIa concentration in microparticle-free plasma with increasing the applied shear stress and exposure time. It is clear that non-physiological shear stress induce a paradoxical phenomenon, in which both activation and shedding of the GPIIb/IIIa on the platelet surface occur simultaneously. This study may offer a new perspective to explain the reason of both increased thrombosis and bleeding events in patients implanted with high shear blood-contacting medical devices. PMID- 26160284 TI - [Peripartum cardiomyopathy]. AB - The peripartum cardiomyopathy is a rare form of dilated cardiomyopathy resulting from alteration of angiogenesis toward the end of pregnancy. The diagnosis is based on the association of clinical heart failure and systolic dysfunction assessed by echocardiography or magnetic resonance imaging. Diagnoses to rule out are myocardial infarction, amniotic liquid embolism, myocarditis, inherited cardiomyopathy, and history of treatment by anthracycline. Risk factors are advance maternal age (>30), multiparity, twin pregnancy, African origin, obesity, preeclampsia, gestational hypertension, and prolonged tocolytic therapy. Treatment of acute phase is identical to usual treatment of acute systolic heart failure. After delivery, VKA treatment should be discussed in case of systolic function <25% because of higher risk of thrombus. A specific treatment by bromocriptine can be initiated on a case-by-case basis. Complete recovery of systolic function is observed in 50% of cases. The mortality risk is low. Subsequent pregnancy should be discouraged, especially if systolic function did not recover. PMID- 26160285 TI - [Major surgery in two days of hospitalization]. AB - A reduction to 2 days the length of stay after a major surgery is possible by enhancing patient empowerment and decreasing morbidity. A rapid patient's empowerment is obtained by the use of means that reduce the impact of the surgical stress and facilitate the recovery. The decrease in postoperative morbidity is obtained by improving the perioperative quality of care. All of these means are gathered in enhanced recovery programs that are clinical pathways designed by a multidisciplinary and multiprofessional team. Regular audits are mandatory for the sustainability of these programs. Organization of a network between hospital and out-of-hospital caregivers is important in order to secure the patient's return home. PMID- 26160286 TI - Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fibrosis in Spontaneously Hypertensive Rats. AB - BACKGROUND: We evaluated the role of the aldosterone blocker spironolactone in attenuating long-term pressure overload-induced cardiac remodeling and heart failure (HF) in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Thirteen month-old male SHR were assigned to control (SHR-C, n=20) or spironolactone (SHR-SPR, 20 mg/kg/day, n=24) groups for six months. Normotensive Wistar-Kyoto rats (WKY, n=15) were used as controls. Systolic blood pressure was higher in SHR groups and unchanged by spironolactone. Right ventricular hypertrophy, which characterizes HF in SHR, was less frequent in SHR-SPR than SHR C. Echocardiographic parameters did not differ between SHR groups. Myocardial function was improved in SHR-SPR compared to SHR-C [developed tension: WKY 4.85+/ 0.68; SHR-C 5.22+/-1.64; SHR-SPR 6.80+/-1.49 g/mm2; -dT/dt: WKY 18.0 (16.0-19.0); SHR-C 20.8 (18.4-25.1); SHR-SPR 28.9 (24.2-34.6) g/mm2/s]. Cardiomyocyte cross sectional area and total collagen concentration (WKY 1.06+/-0.34; SHR-C 1.85+/ 0.63; SHR-SPR 1.28+/-0.39 MUg/mg wet tissue) were greater in SHR-C than WKY and SHR-SPR. Type 3 collagen expression was lower in SHR-C than WKY and unchanged by spironolactone. Soluble collagen, type I collagen, and lysyl oxidase did not differ between groups. CONCLUSION: Early spironolactone treatment decreases heart failure development frequency by improving myocardial systolic and diastolic function and attenuating hypertrophy and fibrosis in spontaneously hypertensive rats. PMID- 26160289 TI - Altered frontal inter-hemispheric resting state functional connectivity is associated with bulimic symptoms among restrained eaters. AB - Theory and research have indicated that restrained eating (RE) increases risk for binge-eating and eating disorder symptoms. According to the goal conflict model, such risk may result from disrupted hedonic-feeding control and its interaction with reward-driven eating. However, RE-related alterations in functional interactions among associated underlying brain regions, especially between the cerebral hemispheres, have rarely been examined directly. Therefore, we investigated inter-hemispheric resting-state functional connectivity (RSFC) among female restrained eaters (REs) (n=23) and unrestrained eaters (UREs) (n=24) following food deprivation as well as its relation to overall bulimia nervosa (BN) symptoms using voxel-mirrored homotopic connectivity (VMHC). Seed-based RSFC associated with areas exhibiting significant VMHC differences was also assessed. Compared to UREs, REs showed reduced VMHC in the dorsal-lateral prefrontal cortex (DLPFC), an area involved in inhibiting hedonic overeating. REs also displayed decreased RSFC between the right DLPFC and regions associated with reward estimation--the ventromedial prefrontal cortex (VMPFC) and posterior cingulate cortex (PCC). Finally, bulimic tendencies had a negative correlation with VMHC in the DLPFC and a positive correlation with functional connectivity (DLPFC and VMPFC) among REs but not UREs. Findings suggested that reduced inter-hemispheric functional connectivity in appetite inhibition regions and altered functional connectivity in reward related regions may help to explain why some REs fail to control hedonically-motivated feeding and experience higher associated levels of BN symptomatology. PMID- 26160288 TI - Cortical contributions to impaired contour integration in schizophrenia. AB - OBJECTIVES: Visual perceptual organization impairments in schizophrenia (SCZ) are well established, but their neurobiological bases are not. The current study used the previously validated Jittered Orientation Visual Integration (JOVI) task, along with fMRI, to examine the neural basis of contour integration (CI), and its impairment in SCZ. CI is an aspect of perceptual organization in which multiple distinct oriented elements are grouped into a single continuous boundary or shape. METHODS: On the JOVI, five levels of orientational jitter were added to non-contiguous closed contour elements embedded in background noise to progressively increase the difficulty in perceiving contour elements as left- or right-pointing ovals. Multi-site fMRI data were analyzed for 56 healthy control subjects and 47 people with SCZ. RESULTS: SCZ patients demonstrated poorer CI, and this was associated with increased activation in regions involved in global shape processing and visual attention, namely the lateral occipital complex and superior parietal lobules. There were no brain regions where controls demonstrated more activation than patients. CONCLUSIONS: CI impairment in this sample of outpatients with SCZ was related to excessive activation in regions associated with object processing and allocation of visual-spatial attention. There was no evidence for basic impairments in contour element linking in the fMRI data. The latter may be limited to poor outcome patients, where more extensive structural and functional changes in the occipital lobe have been observed. PMID- 26160287 TI - Development of common neural representations for distinct numerical problems. AB - How the brain develops representations for abstract cognitive problems is a major unaddressed question in neuroscience. Here we tackle this fundamental question using arithmetic problem solving, a cognitive domain important for the development of mathematical reasoning. We first examined whether adults demonstrate common neural representations for addition and subtraction problems, two complementary arithmetic operations that manipulate the same quantities. We then examined how the common neural representations for the two problem types change with development. Whole-brain multivoxel representational similarity (MRS) analysis was conducted to examine common coding of addition and subtraction problems in children and adults. We found that adults exhibited significant levels of MRS between the two problem types, not only in the intraparietal sulcus (IPS) region of the posterior parietal cortex (PPC), but also in ventral temporal occipital, anterior temporal and dorsolateral prefrontal cortices. Relative to adults, children showed significantly reduced levels of MRS in these same regions. In contrast, no brain areas showed significantly greater MRS between problem types in children. Our findings provide novel evidence that the emergence of arithmetic problem solving skills from childhood to adulthood is characterized by maturation of common neural representations between distinct numerical operations, and involve distributed brain regions important for representing and manipulating numerical quantity. More broadly, our findings demonstrate that representational analysis provides a powerful approach for uncovering fundamental mechanisms by which children develop proficiencies that are a hallmark of human cognition. PMID- 26160290 TI - Promoter Methylation and BDNF and DAT1 Gene Expression Profiles in Patients with Drug Addiction. AB - BACKGROUND: Drug addiction is a brain disorder that has negative consequences for individuals and society. Addictions are chronic relapsing diseases of the brain that are caused by direct drug-induced effects and persevering neuroadaptations at the epigenetic, neuropeptide and neurotransmitter levels. Because the dopaminergic system has a significant role in drug abuse, the purpose of this study was to analyze the methylation and expression profile of brain-derived neurotrophic factor (BDNF) and dopamine transporter (DAT1) genes in individuals with drug addiction. MATERIALS AND METHODS: BDNF and DAT1 promoter methylation were investigated with a methylation-specific polymerase chain reaction (PCR) technique in blood samples from 75 individuals with drug addiction and 65 healthy controls. The expression levels of BDNF and DAT1 were assessed in 12 mRNA samples from the blood of patients and compared to the samples of healthy controls (n = 12) with real-time quantitative reverse transcription PCR. RESULTS: No significant differences were found in the methylation of BDNF and DAT1 between patients and controls, but the relative levels of expression of BDNF and DAT1 mRNA differed significantly in the patients compared to controls (p < 0.0001). CONCLUSION: These results showed that the methylation status of the BDNF and DAT1 genes had no significant function in the processes of drug addiction. PMID- 26160292 TI - Erratum, Vol. 12, May 21 Release. PMID- 26160291 TI - A Leishmania-specific hypothetical protein expressed in both promastigote and amastigote stages of Leishmania infantum employed for the serodiagnosis of, and as a vaccine candidate against, visceral leishmaniasis. AB - BACKGROUND: LiHyV is an antigenic hypothetical protein present in both promastigote and amastigote stages of Leishmania infantum, which was recently identified by an immunoproteomic approach. A recombinant version of this protein (rLiHyV) was evaluated as a diagnostic marker for canine VL (CVL). In addition, the prophylactic efficacy of the rLiHyV protein, and two of its CD8(+) T cell epitopes, has been analyzed in a murine model of visceral leishmaniasis (VL). METHODS: Initially, the rLiHyV protein was evaluated by an ELISA technique for the serodiagnosis of CVL. Secondly, vaccines composed of the recombinant protein and both chemically synthesized peptides, combined with saponin as an adjuvant; were administered subcutaneously into BALB/c mice. The cellular and humoral responses generated by vaccination were evaluated. In addition, the parasite burden and immune response were studied 10 weeks after L. infantum infection. RESULTS: The rLiHyV protein was recognized by antibodies of VL dogs. No cross reactivity was obtained with sera from dogs vaccinated with a Brazilian commercial vaccine, with sera from animals infected with Trypanosoma cruzi, Babesia canis and Ehrlichia canis, or those from non-infected animals living in an endemic area for leishmaniasis. After challenge with L. infantum, spleen cells of BALB/c mice vaccinated with rLiHyV/saponin stimulated with parasite antigens showed a higher production of IFN-gamma, IL-12 and GM-CSF, than the same cells obtained from mice vaccinated with the individual peptides, or mice from control (inoculated with saline or saponin) groups. This Th1-type cellular response observed in rLiHyV/saponin vaccinated mice was accompanied by the induction of parasite-specific IgG2a isotype antibodies. Animals immunized with rLiHyV/saponin showed significant reductions in the parasite burden in the liver, spleen, bone marrow and in the lymph nodes draining the paws relative to control mice. CONCLUSIONS: The present study showed for the first time that the L. infantum LiHyV protein could be considered as a vaccine candidate against L. infantum infection, as well as a diagnostic marker for CVL. PMID- 26160293 TI - Colorectal Cancer Identification Methods Among Kansas Medicare Beneficiaries, 2008-2010. AB - INTRODUCTION: Population-based data are limited on how often colorectal cancer (CRC) is identified through screening or surveillance in asymptomatic patients versus diagnostic workup for symptoms. We developed a process for assessing CRC identification methods among Medicare-linked CRC cases from a population-based cancer registry to assess identification methods (screening/surveillance or diagnostic) among Kansas Medicare beneficiaries. METHODS: New CRC cases diagnosed from 2008 through 2010 were identified from the Kansas Cancer Registry and matched to Medicare enrollment and claims files. CRC cases were classified as diagnostic-identified versus screening/surveillance-identified using a claims based algorithm for determining CRC test indication. Factors associated with screening/surveillance-identified CRC were analyzed using logistic regression. RESULTS: Nineteen percent of CRC cases among Kansas Medicare beneficiaries were screening/surveillance-identified while 81% were diagnostic-identified. Younger age at diagnosis (65 to 74 years) was the only factor associated with having screening/surveillance-identified CRC in multivariable analysis. No association between rural/urban residence and identification method was noted. CONCLUSION: Combining administrative claims data with population-based registry records can offer novel insights into patterns of CRC test use and identification methods among people diagnosed with CRC. These techniques could also be extended to other screen-detectable cancers. PMID- 26160294 TI - Attitudes and Beliefs of Primary Care Providers in New Mexico About Lung Cancer Screening Using Low-Dose Computed Tomography. AB - INTRODUCTION: On the basis of results from the National Lung Screening Trial (NLST), national guidelines now recommend using low-dose computed tomography (LDCT) to screen high-risk smokers for lung cancer. Our study objective was to characterize the knowledge, attitudes, and beliefs of primary care providers about implementing LDCT screening. METHODS: We conducted semistructured interviews with primary care providers practicing in New Mexico clinics for underserved minority populations. The interviews, conducted from February through September 2014, focused on providers' tobacco cessation efforts, lung cancer screening practices, perceptions of NLST and screening guidelines, and attitudes about informed decision making for cancer screening. Investigators iteratively reviewed transcripts to create a coding structure. RESULTS: We reached thematic saturation after interviewing 10 providers practicing in 6 urban and 4 rural settings; 8 practiced at federally qualified health centers. All 10 providers promoted smoking cessation, some screened with chest x-rays, and none screened with LDCT. Not all were aware of NLST results or current guideline recommendations. Providers viewed study results skeptically, particularly the 95% false-positive rate, the need to screen 320 patients to prevent 1 lung cancer death, and the small proportion of minority participants. Providers were uncertain whether New Mexico had the necessary infrastructure to support high quality screening, and worried about access barriers and financial burdens for rural, underinsured populations. Providers noted the complexity of discussing benefits and harms of screening and surveillance with their patient population. CONCLUSION: Providers have several concerns about the feasibility and appropriateness of implementing LDCT screening. Effective lung cancer screening programs will need to educate providers and patients to support informed decision making and to ensure that high-quality screening can be efficiently delivered in community practice. PMID- 26160295 TI - Housing Insecurity and the Association With Health Outcomes and Unhealthy Behaviors, Washington State, 2011. AB - Few studies of associations between housing and health have focused on housing insecurity and health risk behaviors and outcomes. We measured the association between housing insecurity and selected health risk behaviors and outcomes, adjusted for socioeconomic measures, among 8,415 respondents to the 2011 Washington State Behavioral Risk Factor Surveillance System. Housing insecure respondents were about twice as likely as those who were not housing insecure to report poor or fair health status or delay doctor visits because of costs. This analysis supports a call to action among public health practitioners who address disparities to focus on social determinants of health risk behaviors and outcomes. PMID- 26160296 TI - Ru(II)-based complexes with N-(acyl)-N',N'-(disubstituted)thiourea ligands: Synthesis, characterization, BSA- and DNA-binding studies of new cytotoxic agents against lung and prostate tumour cells. AB - Four ruthenium(II)-based complexes with N-(acyl)-N',N'-(disubstituted)thiourea derivatives (Th) were obtained. The compounds, with the general formula trans [Ru(PPh3)2(Th)(bipy)]PF6, interact with bovine serum albumin (BSA) and DNA. BSA binding constants, which were in the range of 3.3-6.5*10(4) M(-1), and the thermodynamic parameters (DeltaG, DeltaH and DeltaS), suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. Also, binding constant by spectrophotometric DNA titration (Kb = 0.8-1.8*10(4) M(-1)) and viscosity studies indicate weak interactions between the complexes and DNA. Cytotoxicity assays against DU-145 (prostate cancer) and A549 (lung cancer) tumour cells revealed that the complexes are more active in tumour cells than in normal (L929) cells, and that they present high cytotoxicity (low IC50 values) compared with the reference metallodrug, cisplatin. PMID- 26160298 TI - Corrigendum. PMID- 26160299 TI - Biomonitoring of metals for air pollution assessment using a hemiepiphyte herb (Struthanthus flexicaulis). AB - This work presents first results on elemental characterization of a parasite plant, Struthanthus flexicaulis, collected in urban, industrial and rural areas of Rio de Janeiro state, Brazil, in order to evaluate this plant as a biomonitor of metals pollution. The results were also compared to those obtained for fine particulate matter (PM2.5) collected from filters in nearby locales. The concentrations of PM2.5 measured in the filters were between 8.0 and 18.0 MUg m( 3); in some places, these measurements were higher than the 10 MUg m(-3), concentration recommended by the World Health Organization (WHO). Samples of the leaves and filters with PM were submitted to acid extraction, and the extracts were employed to determine major elements (Ba, Ca, Fe, K, Mg, P and S) by ICP OES and minor elements (Cr, Cu, La, Mn, Pb, Sr, Ti and Zn) by ICP-MS. Elements' extraction efficiency was evaluated by applying the method to the certified reference materials (CMR) of tomato leaves (NIST 1573(rd)) and urban dust (NIST 1648a). The concentrations of Ca, K and Mg were higher in leaves, while Ba, Ca, K and Zn showed higher concentrations in the PM. As expected, rural sites presented lower metal content. Enrichment factor (EF) and principal component analysis with multiple linear regression analysis (PCA-MLRA) were applied to the concentrations of elements in PM2.5 and in the leaves. Anthropogenic sources could be identified with both tools, which supports the use of S. flexicaulis as a biomonitor. PMID- 26160297 TI - The Soluble Periplasmic Domains of Escherichia coli Cell Division Proteins FtsQ/FtsB/FtsL Form a Trimeric Complex with Submicromolar Affinity. AB - Cell division in Escherichia coli involves a set of essential proteins that assembles at midcell to form the so-called divisome. The divisome regulates the invagination of the inner membrane, cell wall synthesis, and inward growth of the outer membrane. One of the divisome proteins, FtsQ, plays a central but enigmatic role in cell division. This protein associates with FtsB and FtsL, which, like FtsQ, are bitopic inner membrane proteins with a large periplasmic domain (denoted FtsQp, FtsBp, and FtsLp) that is indispensable for the function of each protein. Considering the vital nature and accessible location of the FtsQBL complex, it is an attractive target for protein-protein interaction inhibitors intended to block bacterial cell division. In this study, we expressed FtsQp, FtsBp, and FtsLp individually and in combination. Upon co-expression, FtsQp was co-purified with FtsBp and FtsLp from E. coli extracts as a stable trimeric complex. FtsBp was also shown to interact with FtsQp in the absence of FtsLp albeit with lower affinity. Interactions were mapped at the C terminus of the respective domains by site-specific cross-linking. The binding affinity and 1:1:1 stoichiometry of the FtsQpBpLp complex and the FtsQpBp subcomplex were determined in complementary surface plasmon resonance, analytical ultracentrifugation, and native mass spectrometry experiments. PMID- 26160300 TI - Changes in the levels and variability of halocarbons and the compliance with the Montreal Protocol from an urban view. AB - Ambient levels and variability of major atmospheric halocarbons, i.e. CFC-12, CFC 11, CFC-113, CCl4, CH3CCl3, C2HCl3, and C2Cl4 in a major metropolis (Taipei, Taiwan) were re-investigated after fourteen years by flask sampling in 2012. Our data indicates that the variability expressed as standard deviations (SD) of CFC 113 and CCl4 remained small (2.0 ppt and 1.9 ppt, respectively) for the 10th-90th percentile range in both sampling periods; whereas the variability of CFC-12, CFC 11, C2HCl3, and C2Cl4 measured in 2012 became noticeably smaller than observed in 1998, suggesting their emissions were reduced over time. By comparing with the background data of a global network (NOAA/ESRL/GMD baseline observatories), the ambient levels and distribution of these major halocarbons in Taipei approximated those at a background site (Mauna Loa) in 2012, suggesting that the fingerprint of the major halocarbons in a used-to-be prominent source area has gradually approached to that of the background atmosphere. PMID- 26160301 TI - Impact of ATG-containing reduced-intensity conditioning after single- or double unit allogeneic cord blood transplantation. AB - We analyzed 661 adult patients who underwent single-unit (n = 226) or double-unit (n = 435) unrelated cord blood transplantation (UCBT) following a reduced intensity conditioning (RIC) consisting of low-dose total body irradiation (TBI), cyclophosphamide, and fludarabine (Cy/Flu/TBI200). Eighty-two patients received rabbit antithymocyte globulin (ATG) as part of the conditioning regimen (ATG group), whereas 579 did not (non-ATG group). Median age at UCBT was 54 years, and diagnoses were acute leukemias (51%), myelodysplastic syndrome/myeloproliferative neoplasm (19%), and lymphoproliferative diseases (30%). Forty-four percent of patients were transplanted with advanced disease. All patients received >=4 antigens HLA-matched UCBT. Median number of collected total nucleated cells was 4.4 * 10(7)/kg. In the ATG group, on 64 evaluable patients, ATG was discontinued 1 (n = 27), 2 (n = 20), or > 2 days before the graft infusion (n = 17). In multivariate analyses, the use of ATG was associated with decreased incidence of acute graft-versus-host disease (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.17-0.55; P < .0001), higher incidence of nonrelapse mortality (HR, 1.68; 95% CI, 1.16-2.43; P = .0009), and decreased overall survival (HR, 1.69; 95% CI, 1.19-2.415; P = .003). Collectively, our results suggest that the use of ATG could be detrimental, especially if given too close to graft infusion in adults undergoing UCBT following Cy/Flu/TBI200 regimen. PMID- 26160302 TI - The effects of adding epinephrine to ropivacaine for popliteal nerve block on the duration of postoperative analgesia: a randomized controlled trial. AB - BACKGROUND: Duration of peripheral nerve blocks depends on multiple factors. Both technique and type of local anesthetic used, either with or without adjuncts, may result in different duration times of the block. The purpose of the present study was to compare the duration of postoperative analgesia of 30 mL ropivacaine 0.75 % with or without epinephrine for popliteal sciatic nerve block. METHODS: Thirty eight patients were included to receive ultrasound guided continuous popliteal nerve block with ropivacaine 0.75 % either without (ROPI) or with epinephrine 5 MUg/mL (ROPI-EPI) for ankle fusion, subtalar fusion, or a combination of both. The primary outcome parameter was the duration of postoperative analgesia as reflected by the time to first request for postoperative analgesia (TTFR) through the popliteal nerve catheter. Secondary outcome measures included the onset of sensory and motor block and NRS score for pain at rest and during movement. RESULTS: Thirty patients, 15 in each group, were studied. Eight patients were withdrawn because of specific withdrawal criteria described in the protocol and replaced according to their group allocation. Median [interquartile range] TTFR was 463 [300-1197] min and 830 [397-1128] min for the ROPI vs ROPI-EPI group respectively. Hodges Lehman median difference between groups was 71 min (95 % CI 415 - 473 min). There was no difference in any clinical outcome measure between the groups. CONCLUSION: The results of this study did not show any significant increase in the duration of postoperative analgesia by adding epinephrine to ropivacaine for popliteal nerve block. This may be due to the intrinsic vasoconstrictive properties of ropivacaine. The absence of a significant difference can also be the result of a type II error caused by a large variation in the individual TTFR. TRIAL REGISTRATION: Trial register.nl identifier: NTR3330 , keyword TTFR. PMID- 26160303 TI - Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment. AB - In this study we present the development of an injectable polymeric drug delivery system for subconjunctival treatment of primary open angle glaucoma. The system consists of hyaluronic acid sodium salt (HA), which is commonly used in ophthalmology in anterior segment surgery, and an isocyanate-functionalized 1,2 ethylene glycol bis(dilactic acid) (ELA-NCO). The polymer mixtures with different ratios of HA to ELA-NCO (1/1, 1/4, and 1/10 (v/v)) were investigated for biocompatibility, degradation behavior and applicability as a sustained release system. For the latter, the lipophilic latanoprost ester pro-drug (LA) was incorporated into the HA/ELA-NCO system. In vitro, a sustained LA release over a period of about 60days was achieved. In cell culture experiments, the HA/ELA-NCO (1/1, (v/v)) system was proven to be biocompatible for human and rabbit Tenon's fibroblasts. Examination of in vitro degradation behavior revealed a total mass loss of more than 60% during the observation period of 26weeks. In vivo, LA was continuously released for 152days into rabbit aqueous humor and serum. Histological investigations revealed a marked leuko-lymphocytic infiltration soon after subconjunctival injection. Thereafter, the initial tissue reaction declined concomitantly with a continuous degradation of the polymer, which was completed after 10months. Our study demonstrates the suitability of the polymer resulting from the reaction of HA with ELA-NCO as an injectable local drug delivery system for glaucoma therapy, combining biocompatibility and biodegradability with prolonged drug release. PMID- 26160304 TI - Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO Porter prevents ischemia/reperfusion injury in the mouse liver. AB - We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q10 (CoQ10), an anti-oxidant, to in vivo mitochondria using a MITO Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ10 in the lipid phase of a MITO Porter and optimized the mitochondrial fusogenic activities to produce the CoQ10 MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ10-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ10-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria. Finally, we applied the optimized CoQ10-MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ10-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ10 via MITO Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies. PMID- 26160305 TI - Combinatorial resveratrol and quercetin polymeric micelles mitigate doxorubicin induced cardiotoxicity in vitro and in vivo. AB - Doxorubicin hydrochloride (ADR) is an anthracycline antibiotic used to treat various cancers. However, due to its extensive cardiotoxic side effects a lifetime cumulative dose limit of 450-550 mg/m2 exists. The postulated mechanism of the cardiotoxicity is generation of reactive oxygen and nitrogen species. Natural products like resveratrol (RES), and quercetin (QUE) are known free radical scavengers and have shown cardioprotective effects. However, concurrent dosing of these natural products with ADR is limited due to their low solubility, and low oral bioavailability. We hypothesize that the combination of RES and QUE in Pluronic(r) F127 micelles (mRQ) when co-administered with ADR, will be cardioprotective in vitro and in vivo, while maintaining or increasing the efficacy of ADR against cancer cell lines in vitro. We prepared mRQ micelles capable of retaining 1.1mg/mL and 1.42 mg/mL of RES and QUE respectively. The in vitro release of RES and QUE from the micelles followed first order kinetics over 48h. In vitro cell viability and combination index analysis studies in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2) showed that RES:QUE: ADR at 10:10:1 ratio was synergistic in SKOV-3 cells and antagonistic in H9C2 cells. Caspase 3/7 activity studies indicated that mRQ did not interfere with ADR caspase activity in SKOV-3 cells but significantly decreased it in H9C2 cells. The generation of reactive oxygen species (ROS) in SKOV-3 and H9C2 cells in the presence of mRQ also indicated no changes in ROS activity in SKOV-3 cells but significant scavenging in H9C2 cells. Healthy mice were exposed to acute doses of ADR and ADR with mRQ. Based on biochemical estimations the presence of mRQ with ADR conferred full cardioprotection in these mice. Concurrent administration of mRQ with ADR at 10:10:1 ratio provides a viable strategy to mitigate acute ADR induced cardiotoxicity. PMID- 26160306 TI - Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network. AB - Anticancer treatment using embolic drug-eluting beads (DEBs) has shown multifarious advantages compared to systemic chemotherapy. However, there is a growing need for a better understanding of the physical parameters governing drug elution from embolic devices under physiologically relevant fluidic conditions. In the present study, we investigated the spatiotemporal dynamics of doxorubicin hydrochloride elution from drug-loaded hydrogel embolic beads within a microfluidic device consisting of a network of interconnected microchannels which replicates the architectural properties of microvascular systems. Drug-elution has been investigated experimentally at a single-bead level, using in-house developed microscopy- and spectrofluorimetry-based methods. Results demonstrated that the kinetics of drug-elution and the amount of eluted drug strongly depended on the location of the embolic event within the embolised channel (e.g. fractional amount of eluted drug after 3h was equal to ~0.2 and ~0.6 for completely-confined and partially-confined bead, respectively). Drug-elution from partially-confined bead showed a counterintuitive dependence on the local Reynolds number (and thus on the mean fluid velocity), as a result of dynamic changes in bead compressibility causing the displacement of the bead from the primary embolic site. Conversely, the kinetics of drug-elution from fully confined bead was less affected by the local Reynolds number and bead displayed faster elution from the surface area exposed to the systemic flow, which was associated with the formation of fluid eddies nearby the bead post embolisation. PMID- 26160307 TI - Pulmonary administration of phosphoinositide 3-kinase inhibitor is a curative treatment for chronic obstructive pulmonary disease by alveolar regeneration. AB - Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causing widespread and irreversible alveoli collapse. The discovery of a low molecular-weight compound that induces regeneration of pulmonary alveoli is of utmost urgency to cure intractable pulmonary diseases such as COPD. However, a practically useful compound for regenerating pulmonary alveoli is yet to be reported. Previously, we have elucidated that Akt phosphorylation is involved in a differentiation-inducing molecular mechanism of human alveolar epithelial stem cells, which play a role in regenerating pulmonary alveoli. In the present study, we directed our attention to phosphoinositide 3-kinase (PI3K)-Akt signaling and examined whether PI3K inhibitors display the pulmonary alveolus regeneration. Three PI3K inhibitors with different PI3K subtype specificities (Wortmannin, AS605240, PIK-75 hydrochloride) were tested for the differentiation-inducing effect on human alveolar epithelial stem cells, and Wortmannin demonstrated the most potent differentiation-inducing activity. We evaluated Akt phosphorylation in pulmonary tissues of an elastase-induced murine COPD model and found that Akt phosphorylation in the pulmonary tissue was enhanced in the murine COPD model compared with normal mice. Then, the alveolus-repairing effect of pulmonary administration of Wortmannin to murine COPD model was evaluated using X-ray CT analysis and hematoxylin-eosin staining. As a result, alveolar damages were repaired in the Wortmannin-administered group to a similar level of normal mice. Furthermore, pulmonary administration of Wortmannin induced a significant recovery of the respiratory function, compared to the control group. These results indicate that Wortmannin is capable of inducing differentiation of human alveolar epithelial stem cells and represents a promising drug candidate for curative treatment of pulmonary alveolar destruction in COPD. PMID- 26160308 TI - Supramolecular nanoscale assemblies for cancer diagnosis and therapy. AB - Nanocarriers based on polymers, metals and lipids have been extensively developed for cancer therapy and diagnosis due to their ability to enhance drug accumulation in cancer cells and decrease undesired drug toxicity in healthy tissues. Overcoming multidrug resistance by designing proper drug nanocarriers will improve outcome of existing oncologic treatments such as chemotherapy and radiotherapy. In this article the relation between physicochemical properties and capacity of a nanosystem to deliver therapeutic agents into pathological sites is discussed. Most promising examples of drug delivery systems are reviewed, and, in particular, the design of a carbohydrate based matrix with entrapped gold nanoparticles is highlighted. PMID- 26160311 TI - Fluorescent chemosensors of carbohydrate triols exhibiting TICT emissions. AB - 4-4'-Disubstituted biphenyl boronic acids (BBAs) are push-pull fluorophores with "turn-on" fluorescence properties. Upon carbohydrate triol binding, BBA boronate esters can participate in photon-induced electron transfer, giving a twisted intramolecular charge transfer (TICT) complex. The resulting TICT emissions distinguish between carbohydrates that bind to boron as a diol versus triol unit, thereby revealing stereochemical information about the carbohydrate. PMID- 26160310 TI - Role of bronchoalveolar lavage in the diagnosis of acute exacerbations of idiopathic pulmonary fibrosis: a retrospective study. AB - BACKGROUND: It has been recognized that despite previous stability some patients with idiopathic pulmonary fibrosis (IPF) experience acute clinical deteriorations called acute exacerbations of idiopathic pulmonary fibrosis (AEX-IPF). We hypothesized that pulmonary infection can be excluded based on clinical and laboratory data and that bronchoscopy with BAL is not mandatory in the diagnostic work-up of suspected AEX-IPF. METHODS: In this retrospective study we identified patients with acute respiratory failure who were evaluated for AEX-IPF at the Cleveland Clinic between January 2002 and December 2011. Univariate and multivariate analysis were performed with predefined risk factors and final diagnosis of AEX-IPF and pulmonary infection. All tests were performed at a significance level of 0.05. RESULTS: A total of 77 patients met the study inclusion criteria. Of these patients 47 (61 %) were diagnosed with AEX-IPF. Bronchoscopy was more likely to be performed in patients who were on cytotoxic medications (p < 0.05). In most cases the diagnosis of AEX-IPF versus pulmonary infection was based on combination of other microbiological, clinical, radiologic data and clinical judgment. A total of 10 patients out of 14 (71 %) with a final diagnosis of pulmonary infection were on steroids on admission versus 21 out of 63 patients (33 %) with other final diagnosis (p = 0.024, OR 7.817, 95 % CI 1.31 46.64). CONCLUSIONS: Exclusion of infection in our IPF patient cohort was mostly based on factors other than diagnostic bronchoscopy with BAL. Based on our results we suggested an algorithm for management of IPF patients presenting with acute respiratory failure. PMID- 26160309 TI - Layered superhydrophobic meshes for controlled drug release. AB - Layered superhydrophobic electrospun meshes composed of poly(epsilon caprolactone) (PCL) and poly(glycerol monostearate-co-epsilon-caprolactone) (PGC C18) are described as a local source of chemotherapeutic delivery. Specifically, the chemotherapeutic agent SN-38 is incorporated into a central 'core' layer, between two 'shield' layers of mesh without drug. This mesh is resistant to wetting of the surface and throughout the bulk due to the pronounced hydrophobicity imparted by the high roughness of a hydrophobic polymer, PGC-C18. In serum solution, these meshes exhibit slow initial drug release over 10days corresponding to media infiltrating the shield layer, followed by steady release over >30days, as the drug-loaded core layer is wetted. This sequence of events is supported by X-ray computed tomography imaging of a contrast agent solution infiltrating the mesh. In vitro cytotoxicity data collected with Lewis Lung Carcinoma (LLC) cells are consistent with this release profile, remaining cytotoxic for over 20days, longer than the unlayered version. Finally, after subcutaneous implantation in rats, histology of meshes with and without drug demonstrated good integration and lack of adverse reaction over 28days. The drug release rates, robust superhydrophobicity, in vitro cytotoxicity of SN-38 loaded meshes, and compatibility provide key design parameters for the development of an implantable chemotherapeutic-loaded device for the prevention of local lung cancer recurrence following surgical resection. PMID- 26160312 TI - Valproic acid attenuates the expression of pro-inflammatory cytokines lipopolysaccharide-treated canine peripheral blood mononuclear cells (in vitro) and in a canine endotoxemia model (in vivo). AB - Valproic acid (VPA), a known histone deacetylase inhibitor, has been used as an anticonvulsant in dogs. VPA also has anti-inflammatory properties, but there are no reports on the immunomodulatory effects of VPA in canine endotoxemia. In the present study, we demonstrate that the use of VPA significantly reduces the production of early-phase pro-inflammatory cytokines (TNF-alpha, IL-6) caused by lipopolysaccharide (LPS) stimulation both in vitro and in vivo. For the in vitro study, VPA was evaluated for 24h on LPS (100 ng/ml)-treated canine peripheral blood mononuclear cells (PBMCs) which isolated from 5 healthy Beagle dogs. VPA significantly decreased the mRNA expression of TNF-alpha and IL-6 in a dose dependent manner (p<0.05 for IL-6; p<0.01 for TNF-alpha). Fourteen adult Beagles were studied for in vivo study; nine dogs received a low dose of LPS (10 MUg/kg/h) via continuous IV infusion for 12h to induce endotoxemia whereas 5 dogs received normal saline as controls. Four out of 9 endotoxemic dogs were administered VPA (50mg/kg, IV) at 1h and 12h along with the LPS infusion. Three hours after the first administration of VPA, IL-6 mRNA expressions in PBMCs significantly decreased (p=0.033 vs. LPS group). VPA also significantly decreased the circulating TNF-alpha (p=0.044 vs. LPS group at 3h) and IL-6 protein at 3h (p=0.034 vs. LPS group) and 6h (p=0.026 vs. LPS group) post-treatment. Our study suggests that VPA attenuates the expression of pro-inflammatory cytokines in a canine endotoxemia model in vitro and in vivo. We speculate that valproic acid may be useful for reducing inflammatory cytokine levels in dogs with sepsis. PMID- 26160314 TI - Surfactant-Amino Acid and Surfactant-Surfactant Interactions in Aqueous Medium: a Review. AB - An overview of surfactant-amino acid interactions mainly in aqueous medium has been discussed. Main emphasis has been on the solution thermodynamics and solute solvent interactions. Almost all available data on the topic has been presented in a lucid and simple way. Conventional surfactants have been discussed as amphiphiles forming micelles and amino acids as additives and their effect on the various physicochemical properties of these conventional surfactants. Surfactant surfactant interactions in aqueous medium, various mixed surfactant models, are also highlighted to assess their interactions in aqueous medium. Finally, their applied part has been taken into consideration to interpret their possible uses. PMID- 26160315 TI - Expression of Finger Millet EcDehydrin7 in Transgenic Tobacco Confers Tolerance to Drought Stress. AB - One of the critical alarming constraints for agriculture is water scarcity. In the current scenario, global warming due to climate change and unpredictable rainfall, drought is going to be a master player and possess a big threat to stagnating gene pool of staple food crops. So it is necessary to understand the mechanisms that enable the plants to cope with drought stress. In this study, effort was made to prospect the role of EcDehydrin7 protein from normalized cDNA library of drought tolerance finger millet in transgenic tobacco. Biochemical and molecular analyses of T0 transgenic plants were done for stress tolerance. Leaf disc assay, seed germination test, dehydration assay, and chlorophyll estimation showed EcDehydrin7 protein directly link to drought tolerance. Northern and qRT PCR analyses shows relatively high expression of EcDehydrin7 protein compare to wild type. T0 transgenic lines EcDehydrin7(11) and EcDehydrin7(15) shows superior expression among all lines under study. In summary, all results suggest that EcDehydrin7 protein has a remarkable role in drought tolerance and may be used for sustainable crop breeding program in other food crops. PMID- 26160317 TI - Statistical learning modulates the direction of the first head movement in a large-scale search task. AB - Foraging and search tasks in everyday activities are often performed in large, open spaces, necessitating head and body movements. Such activities are rarely studied in the laboratory, leaving important questions unanswered regarding the role of attention in large-scale tasks. Here we examined the guidance of visual attention by statistical learning in a large-scale, outdoor environment. We used the orientation of the first head movement as a proxy for spatial attention and examined its correspondence with reaction time (RT). Participants wore a lightweight camera on a baseball cap while searching for a coin on the concrete floor of a 64-m(2) outdoor space. We coded the direction of the first head movement at the start of a trial. The results showed that the first head movement was highly sensitive to the location probability of the coin and demonstrated more rapid adjustment to changes in environmental statistics than RTs did. Because the first head movement occurred ten times faster than the search RT, these results show that visual statistical learning affected attentional orienting early in large-scale tasks. PMID- 26160316 TI - The inhibitory effect of locally injected dexmedetomidine on carrageenan-induced nociception in rats. AB - Recent studies showed that the administration of dexmedetomidine relieved hyperalgesia in the presence of neuropathic pain. These findings have led to the hypothesis that the local administration of dexmedetomidine is useful for relieving acute inflammatory nociception, such as postoperative pain. Thus, we evaluated the inhibitory effect of locally injected dexmedetomidine on acute inflammatory nociception. Acute inflammatory nociception was induced by an intraplantar injection of 1% carrageenan into the hindpaws of rats, and dexmedetomidine was also injected combined with carrageenan. The paw withdrawal threshold based on von Frey filament stimulation was measured until 12 h after injection. We compared the area under the time-curve (AUC) between carrageenan and carrageenan with dexmedetomidine. To clarify that the action of dexmedetomidine was via alpha2-adrenoceptors, we evaluated the effect of yohimbine, a selective antagonist of alpha2-adrenoceptors, on the anti nociception of dexmedetomidine. As the results, the intraplantar injection of carrageenan with over 10 MUM dexmedetomidine significantly increased AUC, compared to that with only carrageenan injection. This effect of dexmedetomidine was reversed by the addition of yohimbine to carrageenan and dexmedetomidine. These results demonstrated that the locally injected dexmedetomidine was effective against carrageenan-induced inflammatory nociception via alpha2 adrenoceptors. The findings suggest that the local injection of dexmedetomidine is useful for relieving local acute inflammatory nociception. PMID- 26160318 TI - Spectroscopic study of Gd nanostructures quantum confined in Fe corrals. AB - Low dimensional nanostructures have attracted attention due to their rich physical properties and potential applications. The essential factor for their functionality is their electronic properties, which can be modified by quantum confinement. Here the electronic states of Gd atom trapped in open Fe corrals on Ag(111) were studied via scanning tunneling spectroscopy. A single spectroscopic peak above the Fermi level is observed after Gd adatoms are trapped inside Fe corrals, while two peaks appear in empty corrals. The single peak position is close to the higher energy peak of the empty corrals. These findings, attributed to quantum confinement of the corrals and Gd structures trapped inside, are supported by tight-binding calculations. This demonstrates and provides insights into atom trapping in open corrals of various diameters, giving an alternative approach to modify the properties of nano-objects. PMID- 26160319 TI - Volatile anaesthetics and cardiac protection in abdominal surgery. AB - BACKGROUND: Clinical studies have shown that sevoflurane is cardio-protective in cardiac surgery patients, but this effect is doubtful in general surgery patients. This study has researched the influence of sevoflurane on the perioperative cardiac function and the incidence of cardiac ischaemic events in abdominal surgical patients. METHODS: Out of 80 patients scheduled for elective colorectal surgery, 42 received balanced sevoflurane-fentanyl anaesthesia, while 38 received intravenous midazolam-fentanyl anaesthesia. The cardiac index (CI) and cardiac function index (CFI) were measured by the PiCCO device, and Troponin I levels were measured at the beginning of surgery, as well as 4, 12 and 24 h afterwards. BNP was measured at the beginning of surgery, and 24 h afterwards. The data analysis was conducted using the Mann-Whitney nonparametric test, with statistical significance set at p < 0.05. RESULTS: There was no statistical difference in perioperative Troponin I, BNP, CI and CFI values between the SEVO and TIVA groups throughout the perioperative period. CONCLUSIONS: Sevoflurane had no effect on the cardiac biomarkers Troponin I and BNP, and on the PiCCO parameters of cardiac function in abdominal surgical patients. Further research on the preconditioning effect of volatile anaesthetics in general surgical population should be concentrated on the population of patients with a high perioperative cardiac risk. PMID- 26160320 TI - Pylephlebitis: a Review of 95 Cases. AB - Pylephlebitis, or suppurative thrombophlebitis of the portal mesenteric venous system occurring in the setting of abdominal inflammatory processes, is a rare but deadly disease commonly associated with diverticulitis. We review our institutional experience in the management of patients with this condition. A retrospective review of medical records from 2002 to 2012 was performed. Patients with a portal mesenteric vein thrombosis (PMVT) within 30 days of an intra abdominal inflammatory process were identified and evaluated. Ninety-five patients were included. The mean patient age at presentation was 57 years (range, 24-88). The most common associated processes were pancreatitis (31 %), followed by diverticulitis (19 %). Bacteremia was noted in 34 (44 %) patients. The most common organism cultured was Streptococcus viridans. Antibiotic and anticoagulation therapy was given in 86 (91 %) and 78 (82 %) patients, respectively. Overall, we report an 11 % mortality rate. Albeit rare, pylephlebitis most commonly was manifested in the setting of pancreatitis. Treatment should be individualized to culture results and extent of thrombosis. If diagnosed early and managed appropriately, a favorable outcome is possible. PMID- 26160321 TI - Fast-Track Programs for Liver Surgery: A Meta-Analysis. AB - BACKGROUND AND OBJECTIVES: Plentiful publications have inspected the feasibility of fast-track surgery programs during hepatic surgery, but the potency of these studies has not been discussed profoundly so far. Our goal was to assess the effects of fast-track programs on surgical outcomes compared with traditional surgical plans for liver surgery. METHODS: The following databases were searched: PubMed, Cochrane library, Embase, Science Citation Index Expanded, etc. Studies meeting our inclusion criteria were included. All interrelated data and the methodological quality of included studies were extracted and assessed. We applied risk ratio and weighted mean difference as the estimated effect measures. Sensitivity analysis was performed to perceive the reliability of our findings. RESULTS: Altogether, 14 studies with 1400 patients were analyzed. Meta-analysis of randomized controlled trials demonstrated that implementation of fast-track surgery programs could observably decrease the total length of hospital stay, complication rate, postoperative first flatus time, and hospitalization expense, and did not compromise mortality and readmission rate. The above findings were also in line with the results of case-control studies. CONCLUSIONS: Fast-track surgery programs are feasible and effective for liver surgery. Future studies should optimize fast-track surgery programs catering to liver surgery. PMID- 26160323 TI - Intraductal Papillary Mucinous Neoplasms and the Risk of Diabetes Mellitus in Patients Undergoing Resection Versus Observation. AB - OBJECTIVE: The aim of this study is to determine the prevalence of diabetes mellitus (DM) in patients with intraductal papillary mucinous neoplasm of the pancreas (IPMN) and compare rates of new/progressive DM between IPMN patients undergoing pancreatectomy versus observation. METHODS: Patients diagnosed with IPMN were identified from institutional databases, divided into two groups based on treatment type, pancreatectomy versus clinical observation, and subsequently evaluated. Standard demographic and clinicopathologic variables, fasting glucose, diabetic status, and pancreatic volume data, were obtained and compared between groups. RESULTS: One hundred thirty-four IPMN patients were identified; 103 (77 %) underwent pancreatectomy and 31 (23 %) were observed. Baseline DM rate was 18 % (24/134). This was not different between groups [17 % (17/103) resected vs. 23 % (7/31) observed, p = 0.51]. Median follow-up was 53 months and new/progressive DM occurred in 37 (28 %) patients with no difference between groups [29 (28 %) resected vs. 8 (26 %) observed, p = 0.74]. Among resected patients, degree of dysplasia was associated with increase risk of new/progressive DM [moderate dysplasia OR 5.76 (1.24-26.79) and severe dysplasia OR 9.43 (1.54-57.74), p = 0.04], while procedure type and remnant volume were not. CONCLUSIONS: The incidence and prevalence of DM among patients with IPMN was high and did not differ between resected and observed groups. Degree of dysplasia, not the amount of resected pancreas, was associated with increased risk of DM, suggesting that the presence or development of DM may be a marker of malignant progression. Confirmatory studies are required. PMID- 26160322 TI - Pancreatectomy with Para-Aortic Lymph Node Dissection for Pancreatic Head Adenocarcinoma: Pattern of Nodal Metastasis Spread and Analysis of Prognostic Factors. AB - BACKGROUND: This study investigated the prognostic impact of the exact location of nodal metastases in a subgroup of patients who underwent pancreatectomy with extended lymphadenectomy for head adenocarcinoma, with a special focus on station 16b1. METHODS: Clinical, pathologic, and follow-up details were extracted from our database and analyzed retrospectively. Survival analysis was performed using univariate and multivariate models. We also performed a matched case-control analysis with resected patients who did not receive extended lymphadenectomy and with locally advanced patients. RESULTS: The study population consisted of 67 patients. The rate of station 16b1 metastases was 20.9%. Station 14a-b metastases (OR = 4.28), G3 tumors (OR = 4.03), and number of PLN >= 8 (OR = 4.46) were independently associated with station 16b1 involvement. Among pN1 patients, station 14a-b (HR = 2.60) and station 16b1 metastases (HR = 2.40) were predictors of survival. The median disease-specific survival of 16b1+ patients was 17 months (95% CI 8.47-25.52). In the matched case-control analysis, the survival rates of resected 16b1+ patients was in between pN1/16b1- patients and locally advanced patients. CONCLUSIONS: Metastases to station 16b1 are associated with a decreased survival in comparison with pN1/16b1- patients, yet longer than in matched locally advanced patients. Station 14 can be considered as a "junctional node" to station 16b1. PMID- 26160324 TI - Aggravated restenosis and atherogenesis in ApoCIII transgenic mice but lack of protection in ApoCIII knockouts: the effect of authentic triglyceride-rich lipoproteins with and without ApoCIII. AB - AIM: Previously, our group and others have demonstrated a causative relationship between severe hypertriglyceridaemia and atherogenesis in mice. Furthermore, clinical investigations have shown high levels of plasma Apolipoprotein C-III (ApoCIII) associated with hypertriglyceridaemia and even cardiovascular disease. However, it remains unclear whether ApoCIII affects restenosis in vivo, and whether such an effect is mediated by ApoCIII alone, or in combination with hypertriglyceridaemia. We sought to investigate ApoCIII in restenosis and clarify how smooth muscle cells (SMCs) respond to authentic triglyceride-rich lipoproteins (TRLs) with or without ApoCIII (TRLs +/- ApoCIII). METHODS AND RESULTS: ApoCIII transgenic (ApoCIIItg) and knockout (ApoCIII-/-) mice underwent endothelial denudation to model restenosis. Here, ApoCIIItg mice displayed severe hypertriglyceridaemia and increased neointimal formation compared with wild-type (WT) or ApoCIII-/- mice. Furthermore, increased proliferating cell nuclear antigen (PCNA)-positive cells, Mac-3, and vascular cell adhesion protein-1 (VCAM 1) expression, and 4-hydroxynonenal (4HNE) production were found in lesion sites. ApoCIIItg and ApoCIII-/- mice were then crossed to low-density lipoprotein receptor-deficient (Ldlr-/-) mice and fed an atherogenic diet. ApoCIIItg/Ldlr-/- mice had significantly increased atherosclerotic lesions. However, there was no statistical difference in restenosis between ApoCIII-/- and WT mice, and in atherosclerosis between ApoCIII/Ldlr double knockout and Ldlr-/- mice. SMCs were then incubated in vitro with authentic TRLs +/- ApoCIII isolated from extreme hypertriglyceridaemia glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1-deficient (GPIHBP1-/-) mice crossed with ApoCIIItg or ApoCIII-/- mice. It was shown that TRLs + ApoCIII promoted SMC proliferation, VCAM-1 expression, and reactive oxygen species (ROS) production, and activated the Akt pathway. Scavenging ROS significantly reduced SMC activation caused by TRLs + ApoCIII. CONCLUSIONS: Severe hypertriglyceridaemia resulting from ApoCIII overexpression promotes restenosis and atherosclerosis. Furthermore, we demonstrated that TRLs + ApoCIII promotes SMC proliferation. PMID- 26160325 TI - Platelets and thromboxane receptors: pivotal players in arteriogenesis. PMID- 26160326 TI - Understanding Early Post-Mortem Biochemical Processes Underlying Meat Color and pH Decline in the Longissimus thoracis Muscle of Young Blond d'Aquitaine Bulls Using Protein Biomarkers. AB - Many studies on color biochemistry and protein biomarkers were undertaken in post mortem beef muscles after >=24 hours. The present study was conducted on Longissimus thoracis muscles of 21 Blond d'Aquitaine young bulls to evaluate the relationships between protein biomarkers present during the early post-mortem and known to be related to tenderness and pH decline and color development. pH values at 45 min, 3 h, and 30 h post-mortem were correlated with three, seven, and six biomarkers, respectively. L*a*b* color coordinates 24 h post-mortem were correlated with nine, five, and eight protein biomarkers, respectively. Regression models included Hsp proteins and explained between 47 and 59% of the variability between individuals in pH and between 47 and 65% of the variability in L*a*b* color coordinates. Proteins correlated with pH and/or color coordinates were involved in apoptosis or had antioxidative or chaperone activities. The main results include the negative correlations between pH45 min, pH3 h, and pHu and Prdx6, which may be explained by the antioxidative and phospholipase activities of this biomarker. Similarly, inducible Hsp70-1A/B and MU-calpain were correlated with L*a*b* coordinates, due to the protective action of Hsp70-1A/B on the proteolytic activities of MU-calpain on structural proteins. Correlations existed further between MDH1, ENO3, and LDH-B and pH decline and color stability probably due to the involvement of these enzymes in the glycolytic pathway and, thus, the energy status of the cell. The present results show that research using protein indicators may increase the understanding of early post-mortem biological mechanisms involved in pH and beef color development. PMID- 26160328 TI - Chance fracture in ankylosing spondylitis--not merely by chance! Danger of injudicious use of skull traction. PMID- 26160327 TI - Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC). AB - BACKGROUND AND AIMS: The positive and negative health effects of dietary carbohydrates are of interest to both researchers and consumers. METHODS: International experts on carbohydrate research held a scientific summit in Stresa, Italy, in June 2013 to discuss controversies surrounding the utility of the glycemic index (GI), glycemic load (GL) and glycemic response (GR). RESULTS: The outcome was a scientific consensus statement which recognized the importance of postprandial glycemia in overall health, and the GI as a valid and reproducible method of classifying carbohydrate foods for this purpose. There was consensus that diets low in GI and GL were relevant to the prevention and management of diabetes and coronary heart disease, and probably obesity. Moderate to weak associations were observed for selected cancers. The group affirmed that diets low in GI and GL should always be considered in the context of diets otherwise understood as healthy, complementing additional ways of characterizing carbohydrate foods, such as fiber and whole grain content. Diets of low GI and GL were considered particularly important in individuals with insulin resistance. CONCLUSIONS: Given the high prevalence of diabetes and pre-diabetes worldwide and the consistency of the scientific evidence reviewed, the expert panel confirmed an urgent need to communicate information on GI and GL to the general public and health professionals, through channels such as national dietary guidelines, food composition tables and food labels. PMID- 26160330 TI - Holospinal epidural abscess in a child patient: magnetic resonance imaging findings. PMID- 26160329 TI - Modeling 1-year survival after surgery on the metastatic spine. AB - BACKGROUND CONTEXT: Choosing appropriate surgical patients in the setting of spinal metastases can be challenging. Existing scoring systems focus primarily on patient selection or operative techniques. These scores are limited in their capacity to predict postoperative survival. PURPOSE: The aim was to model survival after spine surgery for metastastic disease. STUDY DESIGN: This was a retrospective multicenter study. PATIENT SAMPLE: All patients who had undergone surgery for the treatment of metastatic spinal disease at one of four tertiary care centers between 2007 and 2013 were included. OUTCOME MEASURE: The outcome measure was 1-year survival after surgery. METHODS: Demographic, medical, oncologic, surgical, and survival data were abstracted from medical records. The effect of predictor variables on survival was evaluated alone and in combination using stepwise logistic regression. Multivariable logistic regression was subsequently used to adjust for confounders. A predictive score was then developed and compared against that of the modified Bauer score alone in terms of prognosticating 1-year survival after surgery. RESULTS: In the time period under investigation, 318 patients underwent surgical intervention for metastastic disease involving the spine, with 307 having data available for analysis. The survival rate at 1 year was 48% (n=142), with a median survival of 10 months. In final adjusted analysis, preoperative modified Bauer score (odds ratio [OR] 3.00; 95% confidence interval [CI] 1.80-5.01; p<.001), ambulatory status (OR 2.47; 95% CI 1.48-4.14; p=.001), and serum albumin (OR 2.80; 95% CI 1.66-4.72; p<.001) were all independent predictors of 1-year survival. The most parsimonious model weighted the modified Bauer score with 2 points and intact ambulatory status and normal serum albumin level with 1 point each, with a ceiling score of 3. The final model using the predictive score was able to explain 74% of the variation in 1-year survival. In contrast, the modified Bauer score alone was only able to explain 64% of the variation in 1-year survival. CONCLUSIONS: This study demonstrates the importance of including factors related to the overall health of a patient, in addition to parameters surrounding their cancer diagnosis, to better prognosticate survival. Our predictive score performed better than the modified Bauer alone and may be used to predict survival after surgical intervention for metastatic disease. LEVEL OF EVIDENCE: III. PMID- 26160331 TI - Atlas fracture with an intact transverse atlantal ligament. PMID- 26160332 TI - Of Caucasians, Asians, and Giraffes: The Influence of Categorization and Target Valence on Social Projection. AB - Past research has indicated that social projection is moderated by categorization, with more projection onto ingroups than onto outgroups. However, a few studies have reported elevated levels of projection even onto outgroups. In line with recent evidence, we hypothesized that positive target valence is the key feature of conditions that elicit projection onto outgroups. The present research extends previous findings by testing whether the effect of valence occurs independent of categorization, with increased levels of projection onto positive ingroup and non-ingroup targets alike. We designed two experiments in which target valence was manipulated by means of evaluative conditioning. Category membership was varied by using faces of Caucasians, Asians, and giraffes. The results supported our valence hypothesis. Counter-intuitively, we also found higher levels of projection onto giraffes than onto humans. These findings suggest that current cognition-based models of projection are not sufficient to account for the whole range of projection phenomena. PMID- 26160333 TI - Benevolent Sexism and Support of Romantic Partner's Goals: Undermining Women's Competence While Fulfilling Men's Intimacy Needs. AB - The current research demonstrates how benevolent sexism functions to undermine women's competence while facilitating men's access to heterosexual intimacy by prompting different support behaviors by men and women. Objective coders rated the support provision exhibited during heterosexual couples' (N = 100) video recorded discussions of each other's personal goals. Men who endorsed benevolent sexism provided more dependency-oriented support, including directly providing plans and solutions and neglecting the recipient's own abilities, which led to their female partners feeling less competent and less positively regarded. In contrast, women who endorsed benevolent sexism provided greater relationship oriented support, characterized by affection and emphasizing the positive relationship outcomes associated with their partner's goals, which led their male partners to perceive greater regard and intimacy in their relationship. This study is the first to investigate how benevolent sexism prompts naturalistic support behaviors that can impede women's capacity for independent success while supporting the fulfillment of men's intimacy needs. PMID- 26160334 TI - Oligonucleotide Therapies: The Past and the Present. AB - In this review we address the development of oligonucleotide (ON) medicines from a historical perspective by listing the landmark discoveries in this field. The various biological processes that have been targeted and the corresponding ON interventions found in the literature are discussed together with brief updates on some of the more recent developments. Most ON therapies act through antisense mechanisms and are directed against various RNA species, as exemplified by gapmers, steric block ONs, antagomirs, small interfering RNAs (siRNAs), micro-RNA mimics, and splice switching ONs. However, ONs binding to Toll-like receptors and those forming aptamers have completely different modes of action. Similar to other novel medicines, the path to success has been lined with numerous failures, where different therapeutic ONs did not stand the test of time. Since the first ON drug was approved for clinical use in 1998, the therapeutic landscape has changed considerably, but many challenges remain until the expectations for this new form of medicine are met. However, there is room for cautious optimism. PMID- 26160337 TI - Civil-Military Engagement: An Empirical Account of Humanitarian Perceptions of Civil-Military Coordination During the Response to Typhoon Haiyan. AB - OBJECTIVE: This study sought to identify how humanitarian actors in natural disasters coordinate (or communicate) with the military to identify the needs of disaster-affected populations, identify how coordination should be undertaken for the delivery of relief goods, perceive the effectiveness of such coordination, perceive the role that training played in preparation for coordinating with the military and the effectiveness of this training, and view the overall civil military engagement and its implications for the independence of the humanitarian sector. METHODS: A survey instrument focused on participant perceptions of the civil-military engagement in response to Typhoon Haiyan in the Philippines was sent to country directors and agency leads who played a role in the response. RESULTS: Although the data supported anecdotal accounts that the coordination between civilian and military actors during the disaster relief efforts in Typhoon Haiyan worked well, they also revealed that fewer than half of the respondents were familiar with the Guidelines on the Use of Foreign Military and Civil Defence Assets in Disaster Relief (the "Oslo Guidelines") and only 12% of respondents thought that the Oslo Guidelines were used to develop organizational policy on humanitarian aid agency engagement with military actors. CONCLUSIONS: Humanitarians felt that international militaries and the Philippines Armed Forces played an important role in ensuring that aid reached people in need, particularly in the early days of the response. However, less than half of the respondents were familiar with the Oslo Guidelines. PMID- 26160335 TI - Close encounters for the first time: Helicase interactions with DNA damage. AB - DNA helicases are molecular motors that harness the energy of nucleoside triphosphate hydrolysis to unwinding structured DNA molecules that must be resolved during cellular replication, DNA repair, recombination, and transcription. In vivo, DNA helicases are expected to encounter a wide spectrum of covalent DNA modifications to the sugar phosphate backbone or the nitrogenous bases; these modifications can be induced by endogenous biochemical processes or exposure to environmental agents. The frequency of lesion abundance can vary depending on the lesion type. Certain adducts such as oxidative base modifications can be quite numerous, and their effects can be helix-distorting or subtle perturbations to DNA structure. Helicase encounters with specific DNA lesions and more novel forms of DNA damage will be discussed. We will also review the battery of assays that have been used to characterize helicase-catalyzed unwinding of damaged DNA substrates. Characterization of the effects of specific DNA adducts on unwinding by various DNA repair and replication helicases has proven to be insightful for understanding mechanistic and biological aspects of helicase function in cellular DNA metabolism. PMID- 26160336 TI - Fine mapping of powdery mildew resistance genes PmTb7A.1 and PmTb7A.2 in Triticum boeoticum (Boiss.) using the shotgun sequence assembly of chromosome 7AL. AB - KEY MESSAGE: A novel powdery mildew resistance gene and a new allele of Pm1 were identified and fine mapped. DNA markers suitable for marker-assisted selection have been identified. Powdery mildew caused by Blumeria graminis is one of the most important foliar diseases of wheat and causes significant yield losses worldwide. Diploid A genome species are an important genetic resource for disease resistance genes. Two powdery mildew resistance genes, identified in Triticum boeoticum (A(b)A(b)) accession pau5088, PmTb7A.1 and PmTb7A.2 were mapped on chromosome 7AL. In the present study, shotgun sequence assembly data for chromosome 7AL were utilised for fine mapping of these Pm resistance genes. Forty SSR, 73 resistance gene analogue-based sequence-tagged sites (RGA-STS) and 36 single nucleotide polymorphism markers were designed for fine mapping of PmTb7A.1 and PmTb7A.2. Twenty-one RGA-STS, 8 SSR and 13 SNP markers were mapped to 7AL. RGA-STS markers Ta7AL-4556232 and 7AL-4426363 were linked to the PmTb7A.1 and PmTb7A.2, at a genetic distance of 0.6 and 6.0 cM, respectively. The present investigation established that PmTb7A.1 is a new powdery mildew resistance gene that confers resistance to a broad range of Bgt isolates, whereas PmTb7A.2 most probably is a new allele of Pm1 based on chromosomal location and screening with Bgt isolates showing differential reaction on lines with different Pm1 alleles. The markers identified to be linked to the two Pm resistance genes are robust and can be used for marker-assisted introgression of these genes to hexaploid wheat. PMID- 26160338 TI - Occult Tumor Cells in Lymph Nodes of Patients with Gastric Cancer: A Systematic Review on Their Prevalence and Predictive Role. AB - BACKGROUND AND AIMS: The presence of lymph node (LN) metastasis is a key prognostic factor for gastric adenocarcinoma. However, even among patients without LN metastasis (N0), recurrence may occur. In some of these cases, occult tumor cells (OTC) are thought to play an important role. We aimed to determine the prevalence of OTC and its clinical relevance. METHODS: We conducted a systematic review of studies in English published until September 2013 that addressed OTC prevalence and/or its clinical relevance. The studies were retrieved from the MEDLINE database. RESULTS: We included 42 studies. The most frequently used methods for detecting OTC were immunohistochemical examination (IHC) and/or polymerase chain reaction (PCR) with a wide range of markers. Using IHC for OTC detection, in patients and in LN, the prevalence varied from 9 to 88% and 0.4 to 42%, respectively. With PCR, it ranged from 17 to 46% in patients, and from 3 to 33% in LN. In the studies assessing the predictive role of OTC in gastric cancer recurrence (n=24), 8 studies found no statistical association, while 18 concluded that OTC presence was associated with poorer prognosis. However, only 6 studies presented a significantly different 5-year survival rate between patients with and without LN micrometastasis. CONCLUSIONS: OTC seems to occur in gastric cancer patients with a variable prevalence, depending on the definition, methods and setting. The majority of the retrieved studies (75%) evaluating the predictive role of OTC conclude that its presence is associated with a worse prognosis. PMID- 26160339 TI - Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage. AB - BACKGROUND/AIMS: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. METHODS: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN) mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. RESULTS: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down regulation of phosphor-nephrin, and an increased binding of c-mip to NF kappaB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-kappaB/RelA in IL-17 treated cells. Persistent activation of NF-kappaB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor nephrin level. CONCLUSION: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip. PMID- 26160340 TI - Use of the distributions of adamantane acids to profile short-term temporal and pond-scale spatial variations in the composition of oil sands process-affected waters. AB - Oil industry produced waters, such as the oils sands process-affected waters (OSPW) of Alberta, Canada, represent a challenge in terms of risk assessment and reclamation due to their extreme complexity, particularly of the organic chemical constituents, including the naphthenic acids (NA). The identification of numerous NA in single samples has raised promise for the use of NA distributions for profiling OSPW. However, monitoring of the success of containment is still difficult, due to the lack of knowledge of the homogeneity (or otherwise) of OSPW composition within, and between, different industry containments. Here we used GC*GC-MS to compare the NA of five OSPW samples from each of two different industries. Short-term temporal and pond-scale spatial variations in the distributions of known adamantane acids and diacids and other unknown tricyclic acids were examined and a statistical appraisal of the replicate data made. The presence/absence of individual acids easily distinguished the OSPW NA of one industry from those of the other. The proportions of tricyclic acids with different carbon numbers also varied significantly between the OSPW of the two industries. The pond-scale spatial variation in NA in OSPW samples was higher than the short-term (2 weeks) temporal variations. An OSPW sample from an aged pond was exceptionally high in the proportion of C15,16,17 compounds, possibly due to increased biotransformation. Such techniques could possibly also help to distinguish different sources of NA in the environment. PMID- 26160341 TI - Early Discrimination between Transient and Permanent Congenital Hypothyroidism in Children with Eutopic Gland. AB - AIM: To analyze the factors that might allow an early discrimination between permanent (P) and transient (T) congenital hypothyroidism (CH). METHODS: Clinical, biochemical and imaging data of 64 children with eutopic gland, who were positively screened and treated for CH during the period 1998-2011, were retrospectively analyzed. RESULTS: During a 3-year treatment period, the mean doses of L-thyroxine (L-T4) per kilogram of body weight at various times were significantly lower in the 46 children with T CH than in the remaining 18 with P CH. No patients with T CH had required any increment of the doses of L-T4 per kilogram of body weight to maintain normal thyroid-stimulating hormone levels over time, whereas 16/18 children with P CH during the same period had needed some dose increments (p < 0.0001). CONCLUSIONS: (a) L-T4 requirements >4.9 ug/kg/day at 12 months or >4.27 ug/kg/day at 24 months are highly suggestive of P CH, irrespective of gland ultrasonography; (b) L-T4 requirements <1.7 ug/kg/day at 12 months or <1.45 ug/kg/day at 24 months are highly suggestive of T CH, at least in the cases with eutopic gland, and (c) the analysis of L-T4 requirements during the first years of treatment might allow an early discrimination between T and P CH in the cases with eutopic gland. PMID- 26160342 TI - Olfactory discrimination and generalization of ammonium nitrate and structurally related odorants in Labrador retrievers. AB - A critical aspect of canine explosive detection involves the animal's ability respond to novel, untrained odors based on prior experience with training odors. In the current study, adult Labrador retrievers (N = 15) were initially trained to discriminate between a rewarded odor (vanillin) and an unrewarded odor (ethanol) by manipulating scented objects with their nose in order to receive a food reward using a canine-adapted discrimination training apparatus. All dogs successfully learned this olfactory discrimination task (>=80 % correct in a mean of 296 trials). Next, dogs were trained on an ammonium nitrate (AN, NH4NO3) olfactory discrimination task [acquired in 60-240 trials, with a mean (+/-SEM) number of trials to criterion of 120.0 +/- 15.6] and then tested for their ability to respond to untrained ammonium- and/or nitrate-containing chemicals as well as variants of AN compounds. Dogs did not respond to sodium nitrate or ammonium sulfate compounds at rates significantly higher than chance (58.8 +/- 4.5 and 57.7 +/- 3.3 % correct, respectively). Transfer performance to fertilizer grade AN, AN mixed in Iraqi soil, and AN and flaked aluminum was significantly higher than chance (66.7 +/- 3.2, 73.3 +/- 4.0, 68.9 +/- 4.0 % correct, respectively); however, substantial individual differences were observed. Only 53, 60, and 64 % of dogs had a correct response rate with fertilizer-grade AN, AN and Iraqi soil, and AN and flaked aluminum, respectively, that were greater than chance. Our results suggest that dogs do not readily generalize from AN to similar AN-based odorants at reliable levels desired for explosive detection dogs and that performance varies significantly within Labrador retrievers selected for an explosive detection program. PMID- 26160343 TI - Nest sanitation elicits egg discrimination in cuckoo hosts. AB - Nest sanitation is a nearly universal behavior in birds, while egg discrimination is a more specific adaptation that has evolved to counter brood parasitism. These two behaviors are closely related with nest sanitation being the ancestral behavior, and it has been hypothesized to constitute a preadaptation for egg discrimination. However, previous studies found little evidence to support this hypothesis. Here, we conducted an empirical test of the association between nest sanitation and egg discrimination in the barn swallow (Hirundo rustica) by inserting a single non-mimetic model egg or a non-mimetic model egg plus half a peanut shell into host nests. Compared to the rejection rate of single model eggs, barn swallows significantly increased egg rejection frequency if a half peanut shell was simultaneously introduced. Our result for the first time shows the impact of nest sanitation on egg discrimination and demonstrates that nest sanitation can elicit egg discrimination in hosts of brood parasites. This study provided evidence for nest sanitation being a preadaptation to egg discrimination by facilitating egg rejection, thereby significantly advancing our understanding of avian cognition of foreign objects. Furthermore, we suggest that egg discrimination behavior in many accepters and intermediate rejecters may be lost or diluted. Such egg discrimination can be elicited and restored after nest sanitation, implying a sensitive and rapid phenotypic response to increased risk of parasitism. Our study offers a novel perspective for investigating the role of so-called intermediate rejecter individuals or species in the long-term coevolutionary cycle between brood parasites and their hosts. PMID- 26160344 TI - Excitation-resolved cone-beam x-ray luminescence tomography. AB - Cone-beam x-ray luminescence computed tomography (CB-XLCT), as an emerging imaging technique, plays an important role in in vivo small animal imaging studies. However, CB-XLCT suffers from low-spatial resolution due to the ill posed nature of reconstruction. We improve the imaging performance of CB-XLCT by using a multiband excitation-resolved imaging scheme combined with principal component analysis. To evaluate the performance of the proposed method, the physical phantom experiment is performed with a custom-made XLCT/XCT imaging system. The experimental results validate the feasibility of the method, where two adjacent nanophosphors (with an edge-to-edge distance of 2.4 mm) can be located. PMID- 26160345 TI - On involvement of transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells, activator protein-1 and signal transducer and activator of transcription-3 in photodynamic therapy-induced death of crayfish neurons and satellite glial cells. AB - Photodynamic therapy (PDT) is currently used in the treatment of brain tumors. However, not only malignant cells but also neighboring normal neurons and glial cells are damaged during PDT. In order to study the potential role of transcription factors-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), activator protein (AP-1), and signal transducer and activator of transcription-3 (STAT-3)-in photodynamic injury of normal neurons and glia, we photosensitized the isolated crayfish mechanoreceptor consisting of a single sensory neuron enveloped by glial cells. Application of different inhibitors and activators showed that transcription factors NF-kappaB (inhibitors caffeic acid phenethyl ester and parthenolide, activator betulinic acid), AP-1 (inhibitor SR11302), and STAT-3 (inhibitors stattic and cucurbitacine) influenced PDT induced death and survival of neurons and glial cells in different ways. These experiments indicated involvement of NF-kappaB in PDT-induced necrosis of neurons and apoptosis of glial cells. However, in glial cells, it played the antinecrotic role. AP-1 was not involved in PDT-induced necrosis of neurons and glia, but mediated glial apoptosis. STAT-3 was involved in PDT-induced apoptosis of glial cells and necrosis of neurons and glia. Therefore, signaling pathways that regulate cell death and survival in neurons and glial cells are different. Using various inhibitors or activators of transcription factors, one can differently influence the sensitivity and resistance of neurons and glial cells to PDT. PMID- 26160346 TI - Microscope-integrated optical coherence tomography for image-aided positioning of glaucoma surgery. AB - Most glaucoma surgeries involve creating new aqueous outflow pathways with the use of a small surgical instrument. This article reported a microscope integrated, real-time, high-speed, swept-source optical coherence tomography system (SS-OCT) with a 1310-nm light source for glaucoma surgery. A special mechanism was designed to produce an adjustable system suitable for use in surgery. A two-graphic processing unit architecture was used to speed up the data processing and real-time volumetric rendering. The position of the surgical instrument can be monitored and measured using the microscope and a grid-inserted image of the SS-OCT. Finally, experiments were simulated to assess the effectiveness of this integrated system. Experimental results show that this system is a suitable positioning tool for glaucoma surgery. PMID- 26160348 TI - Obsessive-Compulsive Personality Traits in Youth with Obsessive-Compulsive Disorder. AB - While interest in the relationship between obsessive-compulsive disorder (OCD) and obsessive compulsive personality disorder has increased, there are currently no studies that have examined the presence of obsessive compulsive personality traits (OCPTs) in youth. The current study sought to determine the latent factors and psychometric properties of a modified version of the Childhood Retrospective Perfectionism Questionnaire (CHIRP) and examine the correlates of specific OCPTs (e.g., rigidity, perfectionism) in youth with OCD. Participants included 96 treatment-seeking youth diagnosed with primary OCD (and a parent). Parents and youth completed measures of OCPTs, OCD severity, depression, and disability. A confirmatory factor analysis of the modified CHIRP resulted in a two-factor model: perfectionism and preoccupation with details. The CHIRP and its subscales demonstrated acceptable internal consistency and preliminary evidence for convergent and divergent validity. Obsessive compulsive traits in youth were also found to be associated with the checking, symmetry and contamination symptom dimensions. PMID- 26160347 TI - Intraoperative near-infrared fluorescence imaging and spectroscopy identifies residual tumor cells in wounds. AB - Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14/15 canines with a mean fluorescence signal-to-background ratio (SBR) of ~16 . Ten animals showed no residual tumor cells in the wound bed (mean SBR<2 , P<0.001 ). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15 , and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations. PMID- 26160350 TI - Corrigendum: PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase. PMID- 26160349 TI - Efficacy of fluralaner flavored chews (Bravecto) administered to dogs against the adult cat flea, Ctenocephalides felis felis and egg production. AB - BACKGROUND: Fluralaner is a potent insecticide and acaricide with rapid and persistent efficacy. This study measured the efficacy of fluralaner flavored chews (Bravecto(r), Merck Animal Health) administered to dogs against adult Ctenocephalides felis felis and egg production. METHODS: Twelve purpose-bred dogs were randomly allocated to two groups of six dogs each. Dogs in treatment group 1 were administered a single fluralaner flavored chew to achieve a minimum dose of at least 25 mg/kg while treatment group 2 served as untreated controls. On Days 2, 28, 56, 84, 91, 98, 105, 112, and 120 post-treatment, each dog was infested with approximately 200 unfed cat fleas, C. felis felis (KS1 strain). Forty-eight hours after treatment and 48 h after each infestation, eggs were collected over a 3-h period, counted and viability determined. Dogs were combed to remove any remaining fleas. RESULTS: Treatment of dogs with oral fluralaner provided a 100% reduction in flea counts 48 h after treatment and within 48 h of every post treatment infestation through Day122. Egg production from fluralaner treated dogs was reduced by 99.9% (two eggs from one dog) within 48 h after treatment and not a single egg (100% efficacy) was thereafter collected from treated dogs. Adult flea counts and egg production from the fluralaner-treated dogs were significantly lower than for non-treated controls at all post-treatment evaluations (P < 0.001). The two eggs collected from the single treated dog 48 h after treatment did not produce any adult fleas. As no additional eggs were collected from treated dogs, no viability assessment was performed. CONCLUSIONS: A single oral dose of fluralaner flavored chews provided 100% efficacy against repeated flea infestations on dogs for 4 months. Fluralaner reduced egg production of activity reproducing female fleas by 99.9% and then killed every single female flea before any eggs could be produced following each subsequent re infestation for the entire 122-day evaluation period. PMID- 26160351 TI - Stem Cell Depletion by Global Disorganization of the H3K9me3 Epigenetic Marker in Aging. AB - Epigenomic change and stem cell exhaustion are two of the hallmarks of aging. Accumulation of molecular damage is thought to underlie aging, but the precise molecular composition of the damage remains controversial. That some aging phenotypes, especially those that result from impaired stem cell function, are reversible suggest that such "damage" is repairable. Evidence is accumulating that dysfunction in aging stem cells results from increasing, albeit, subtle disorganization of the epigenome over time. Zhang et al. (2015) report that decreasing levels of WRN, Werner's syndrome (WS) helicase, with increasing age results in loss of heterochromatin marks in mesenchymal stem cells (MSCs) and correlates with an increased rate of cellular senescence. Although WRN plays a role in DNA repair, WRN exerted its effects on aging via maintaining heterochromatin, evidenced by reduced levels of interacting chromatin regulators heterochromatin protein 1alpha (HP1alpha), suppressor of variegation 3-9 homolog 1 (SUV39H1), and lamina-associated polypeptide 2beta (LAP2beta) as well as modified histone H3K9me3. Reducing expression of chromatin modeling co-factors SUV39H1 or HP1alpha in wild-type MSCs recapitulates the phenotype of WRN deficiency, resulting in reduced H3K9me3 levels and increased senescence without induction of markers of DNA damage, suggesting that chromatin disorganization and not DNA damage is responsible for the pathology of WS during aging in animals. Ectopic expression of HP1alpha restored H3K9me3 levels and repressed senescence in WRN-deficient MSCs. That HP1alpha can also suppress senescence in Hutchinson Gilford progeria syndrome (HGPS) and extend life span in flies when over expressed suggests that HP1alpha and H3K9me3 play conserved roles in maintenance of cell state. H3K9me3 levels are dynamic and expected to be potentially responsive to manipulation by extrinsic factors. Recent reports that migration inhibitory factor (MIF) or periodic fasting rejuvenate old MSCs provide the opportunity to link intrinsic and extrinsic mechanisms of aging in novel and potentially medically important ways and may lead to anti-aging treatments that reorganize the epigenome to rejuvenate cells and tissues. PMID- 26160353 TI - GPR143 Gene Mutations in Five Chinese Families with X-linked Congenital Nystagmus. AB - The ocular albinism type I (OA1) is clinically characterized by impaired visual acuity, nystagmus, iris hypopigmentation with translucency, albinotic fundus, and macular hypoplasia together with normally pigmented skin and hair. However, it is easily misdiagnosed as congenital idiopathic nystagmus in some Chinese patients with OA1 caused by the G-protein coupled receptor 143 (GPR143) gene mutations. Mutations in the FERM domain-containing 7 (FRMD7) gene are responsible for the X linked congenital idiopathic nystagmus. In this study, five Chinese families initially diagnosed as X-linked congenital nystagmus were recruited and patients underwent ophthalmological examinations. After direct sequencing of the FRMD7 and GPR143 genes, five mutations in GPR143 gene were detected in each of the five families, including a novel nonsense mutation of c.333G>A (p.W111X), two novel splicing mutations of c.360+1G>C and c.659-1G>A, a novel small deletion mutation of c.43_50dupGACGCAGC (p.L20PfsX25), and a previously reported missense mutation of c.703G>A (p.E235K). Optical coherence tomography (OCT) examination showed foveal hypoplasia in all the affected patients with nystagmus. Our study further expands the GPR143 mutation spectrum and contributes to the study of GPR143 molecular pathogenesis. Molecular diagnosis and optical coherence tomography (OCT) are two useful tools for differential diagnosis. PMID- 26160355 TI - Oral cholera vaccine protects against endemic disease, real life trial shows. PMID- 26160352 TI - Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease. AB - BACKGROUND: The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD. METHODS: Thirty-one CD patients and 7 controls were enrolled. Circulating CD133(+) and CD34(+) HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3(+) lymphoid cells) and the putative ISC compartment (CD133(+) and Lgr5(+) epithelial cells). RESULTS: At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal. CONCLUSIONS: In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission. PMID- 26160354 TI - The association between serum uric acid levels, metabolic syndrome and cardiovascular disease in middle aged and elderly Chinese: results from the DYSlipidemia International Study. AB - BACKGROUND: To explore the association between serum uric acid (SUA) levels, metabolic syndrome (MetS) and cardiovascular disease (CVD) in patients treated with lipid-lowering agents from multiple centers in China. METHOD: We investigated 15,478 participants who had been documented with recorded SUA in the DYSlipidemia International Study which included 25,697 patients, aged 45 years old or older, who were treated with lipid-lowering agents from 122 centers between April 2012 and October 2012. Logistic regression analysis was performed to examine the association between SUA levels, MetS and CVD. RESULT: After adjusting for multi-variables, hyperuricemia (the highest category of SUA level) showed a significantly higher risk of MetS compared to the lowest category[according to NCEP-ATPIII criteria, odds ratio (OR) 1.51, 95 % confidence interval (CI) (1.30,1.74) in men, OR 2.35 95 % CI (2.00,2.75) in women; and according to IDF criteria, OR 1.40 95 % CI (1.20,1.63) in men, OR 1.65 95 % CI (1.41,1.94) in women]. In addition, elevated SUA concentration was shown to be associated with coronary heart disease (CHD) (OR 1.26 95 % CI (1.09, 1.45) in men, and OR 1.27, 95 % CI (1.07, 1.50) in women) and heart failure (HF) (OR 1.61 95 % CI (1.15, 2.24) in men, and OR 1.91, 95 % CI (1.29, 2.82) in women). CONCLUSION: Our research suggested a positive association between SUA levels and MetS in Chinese patients receiving lipid-lowering therapy. Elevated SU levels were positively associated independently of measured confounders to CHD and HF. PMID- 26160357 TI - Pharmacokinetics and Tolerability of Exenatide Delivered by 7-Day Continuous Subcutaneous Infusion in Healthy Volunteers. AB - INTRODUCTION: Small peptides are approved as treatments for type 2 diabetes mellitus and may have utility in metabolic diseases. These peptides often have short half-lives requiring delivery either as a sustained-release formulation or via a device. The opportunity to study their pharmacokinetics using simple solution formulations delivered by continuous subcutaneous infusion may facilitate the drug development process. METHODS: Here, we investigated the systemic exposure of an exemplar peptide (exenatide) when infused in healthy subjects using a Paradigm((r)) RevelTM insulin infusion pump (Medtronic MiniMed). Four infusion regimens were tested: Constant 24-h infusion (16.5 MUg/day), constant 7-day infusion (25.5 MUg/day in Cohort 2), and two different 7-day escalation regimens (ranging from 7 to 58.5 MUg/day in Cohort 1 and 25.5-58.5 MUg/day in Cohort 3). RESULTS: While the overall exenatide pharmacokinetics were in line with those expected, the observed within-subject concentration variability was considerable. CONCLUSION: Our work identifies sources of potential pharmacokinetic variability relating to the method of delivery and the drug's formulation that will be valuable to investigators contemplating the delivery of peptides via insulin infusion pumps. FUNDING: GlaxoSmithKline. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01857895. PMID- 26160356 TI - Prevalence of dyslalias in 8 to 16 year-old students with anterior open bite in the municipality of Envigado, Colombia. AB - BACKGROUND: Anterior open bite AOB is the most common malocclusion associated with speech disorders and the literature has shown that problems of occlusion involve all oral functions. AOB not only produce aesthetic and occlusal problems for the patient and modifies the union of the lips, tongue, teeth, palate, palatal rugae and oropharynx, and thus affecting the ability to communicate well with their surroundings. The prevalence of AOB in children and adolescent in our population is unknown. Furthermore, the most frequent type of dyslalias in children with this malocclusion is also unknown. Therefore, the aim of the study was to describe the frequency and types of dyslalia in students between 8-16 years with AOB, as well as the difference in the types of dyslalia according to the magnitude of AOB. METHODS: A cross-sectional study was conducted. Clinical assessment of AOB in students from the municipality of Envigado, Colombia, was performed. Students from 8 to 16 years of age were examined during the second semester of 2011 and first semester of 2012. Phonoaudiological assessment was carried out in students in the mixed or permanent dentition. Exclusion criteria included children with history of systemic disease, altered skeletal development, neurological and psychiatric disorders, and residents in other departments. In addition, students undergoing orthodontic treatment at the time of evaluation or with history of previous orthodontic treatment, as well as those who did not cooperate with the oral cavity evaluation, were excluded. RESULTS: Six thousand one hundred sixty five children were evaluated. One hundred sixty six presented AOB (prevalence: 2.7 %; 95 % CI: 2.28-3.10). Thirty four students were excluded. 26.5 % of the sample presented mild AOB, 66.7 % moderate, and 6.8 % severe. Some type of dyslalia was found in 77.4 % of the students, being distortion (75.8 %) the most common. The most frequently altered phonemes were: / d / t / s / ch / n /. No significant association between different types of dyslalia and AOB severity (p-value = 0.974) was found. CONCLUSION: Prevalence of AOB in Envigado is low (2.7 %). Phonation alterations are very common in children with AOB (77.8 %), and distortion is the most frequent type of dyslalia (75.8 %). In order to diagnose and treat occlusal and phonetic problems, and to avoid possible recurrence, interdisciplinary approach is recommended. PMID- 26160358 TI - Twenty years of the Centre for Evidence-based Dentistry. PMID- 26160359 TI - Two reviews of full crown restorations. PMID- 26160360 TI - Acceptance, Prevalence and Indications for Robot-Assisted Laparoscopy - Results of a Survey Among Urologists in Germany, Austria and Switzerland. AB - BACKGROUND: Robotic-assisted laparoscopy (RAL) is being widely accepted in the field of urology as a replacement for conventional laparoscopy (CL). Nevertheless, the process of its integration in clinical routines has been rather spontaneous. OBJECTIVE: To determine the prevalence of robotic systems (RS) in urological clinics in Germany, Austria and Switzerland, the acceptance of RAL among urologists as a replacement for CL and its current use for 25 different urological indications. MATERIALS AND METHODS: To elucidate the practice patterns of RAL, a survey at hospitals in Germany, Austria and Switzerland was conducted. All surgically active urology departments in Germany (303), Austria (37) and Switzerland (84) received a questionnaire with questions related to the one-year period prior to the survey. RESULTS: The response rate was 63%. Among the participants, 43% were universities, 45% were tertiary care centres, and 8% were secondary care hospitals. A total of 60 RS (Germany 35, Austria 8, Switzerland 17) were available, and the majority (68%) were operated under public ownership. The perception of RAL and the anticipated superiority of RAL significantly differed between robotic and non-robotic surgeons. For only two urologic indications were more than 50% of the procedures performed using RAL: pyeloplasty (58%) and transperitoneal radical prostatectomy (75%). On average, 35% of robotic surgeons and only 14% of non-robotic surgeons anticipated RAL superiority in some of the 25 indications. CONCLUSIONS: This survey provides a detailed insight into RAL implementation in Germany, Austria and Switzerland. RAL is currently limited to a few urological indications with a small number of high-volume robotic centres. These results might suggest that a saturation of clinics using RS has been achieved but that the existing robotic capacities are being utilized ineffectively. The possible reasons for this finding are discussed, and certain strategies to solve these problems are offered. PMID- 26160361 TI - Long-term results of total colonic agangliosis patients treated by preservation of the aganglionic right hemicolon and the ileo-cecal valve. AB - PURPOSE: In 1989, Sauer introduced a technique to treat patients with total colonic aganglionosis (TCA) where he preserved the ileo-cecal valve and the right hemicolon to retain water and electrolyte absorption. This report examines the long-term outcome of patients who underwent this technique. METHODS: All TCA patients treated between 1981 and 2005 according to Sauer were invited in 2013 to participate in a questionnaire survey to assess their long-term outcome focusing on bowel function and quality of life (QoL), using standardized scores. RESULTS: Of eight TCA patients (2 females, 6 males), seven participated in the follow-up survey (median follow-up time 13.5 years (range 8-31.6). Early postoperative complications involving bouts of enterocolitis in 3 and anal strictures in 5 patients ceased with age. Bowel movements ranged from median 3-4 times a day (range 1-8). Bowel-function score (BFS) was reduced in 6 patients (median 16 points, range 8-19, max 20), who also reported soiling incidences with the need for night-time protective aids in two. QoL assessment, however, documented a good outcome with a median score of 10 points (range 7-13, max 13). CONCLUSION: This long-term investigation of TCA patients treated according to Sauer's technique documented a good QoL despite a reduced BFS. PMID- 26160362 TI - Body shape index in comparison with other anthropometric measures in prediction of total and cause-specific mortality. AB - BACKGROUND: The association of body mass index (BMI) with mortality remains controversial among the middle-aged and elderly. Moreover, the contribution of other anthropometric measures to predict mortality is unclear. METHODS: We assessed the association of BMI, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and a body shape index (ABSI=WC/(BMI(2/3)*height(1/2))) with total, cardiovascular and cancer mortality by using Cox proportion hazard models among 2626 men and 3740 women from the prospective population-based Rotterdam Study. Predictive performance was assessed through informativeness, c-statistic, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). RESULTS: During 22 years of follow-up, 3675 deaths from all-causes, 1195 from cardiovascular disease, and 873 from cancer occurred. In the multivariable model, ABSI showed a stronger association with mortality compared with BMI, WC, WHtR and WHR. HRs and CIs (95% CIs) for total mortality per 1 SD increase in ABSI were 1.15 (1.09 to 1.21) for men and 1.09 (1.04 to 1.14) for women. For cardiovascular and cancer mortality, these HRs (95% CI) were 1.18 (1.08 to 1.29) and 1.10 (0.99 to 1.22) for men, 1.04 (0.96 to 1.12) and 1.18 (1.07 to 1.30) for women, respectively. The models including ABSI did not increase the c-statistics. Among men, in prediction of total mortality the model including ABSI was more informative (chi(2)=26.4) and provided improvement in risk stratification (IDI 0.003, 95% CI 0.001 to 0.005; cNRI 0.13, 95% CI 0.06 to 0.21). CONCLUSIONS: In our population-based study, among different anthropometric measures, ABSI showed a stronger association with total, cardiovascular and cancer mortality. However, the added predictive value of ABSI in prediction of mortality was limited. PMID- 26160363 TI - Body-worn monitors: a lot done, more to do. PMID- 26160364 TI - Latest QSAR study of adenosine Alpha2Beta receptor affinity of xanthines and deazaxanthines. AB - Adenosine, a widespread and endogenous nucleoside that acts as a powerful neuromodulator in the nervous system, is a promising therapeutic target in a wide range of conditions. The structural similarity between xanthine derivatives and neurotransmitter adenosine has led to the derivatives of the heterocyclic ring being among the most abundant chemical classes of ligand antagonists of adenosine receptor subtypes. Small changes in the xanthine scaffold have resulted in a wide array of adenosine receptor antagonists. In this work, we developed a QSAR model for the [Formula: see text] subtype, which is, as yet, not well characterized, with two purposes in mind: to predict adenosine [Formula: see text] antagonist activity and to offer a substructural interpretation of this group of xanthines. The QSAR model provided good classifications of both the test and external sets. In addition, most of the contributions to adenosine [Formula: see text] receptor affinity derived by subfragmentation of the molecules in the training set agree with the relationships observed in the literature. These two factors mean that this QSAR ensemble could be used as a model to predict future adenosine [Formula: see text] antagonist candidates. PMID- 26160365 TI - Myocardial perfusion is impaired in asymptomatic renal and liver transplant recipients: a cardiovascular magnetic resonance study. AB - BACKGROUND: Myocardial ischemia is a major cause of death in chronic kidney disease (CKD) patients, which can be caused by either epicardial or microvascular coronary artery disease (CAD). Although renal transplantation improves survival, cardiovascular disease remains a major cause of mortality in post renal transplant recipients, including those with no significant epicardial CAD pre transplant. We aim to utilize stress cardiovascular magnetic resonance (CMR) and MR coronary angiography (MRCA) to assess silent myocardial ischemia and epicardial CAD in renal transplant recipients. METHODS: Forty-five subjects: twenty renal transplant (RT) with no known CAD, fifteen liver transplant (LT) controls without prior CKD and no known CAD, and ten hypertensive (HT) controls underwent stress perfusion CMR and MRCA. RESULTS: A total of 1308 myocardial segments (576 of RT, 468 of LT, and 264 of HT) were compared using mixed linear modeling. Left ventricular mass index, septal diameter and presence of diabetes mellitus were similar between the groups. The mean transmural MPRI was significantly lower in the RT and LT groups compared to HT controls (1.19 +/- 0.50 in RT versus 1.23 +/- 0.36 in LT versus 2.04 +/- 0.32 in HT controls, p < 0.0001), in the subepicardium (1.33 +/- 0.57 in RT versus 1.30 +/- 0.33 in LT versus 2.01 +/- 0.30 in HT controls, p < 0.001), and in the subendocardium (1.19 +/- 0.54 in RT versus 1.11 +/- 0.31 in LT versus 1.85 +/- 0.34 in HT controls, p < 0.0001). Seven (35%) RT and five (33%) LT had significant epicardial CAD compared to none in HT controls, p = 0.12. One RT and one LT had LGE suggesting sub-endocardial infarction. CONCLUSIONS: RT recipients have impaired myocardial perfusion independent of LVH or diabetes mellitus. The impaired myocardial perfusion in RT is similar to LT without prior renal disease, thus unlikely related to previous CKD. It is not fully explained by the presence of significant epicardial CAD, and therefore most likely represents microvascular CAD. PMID- 26160366 TI - Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults: The Cardiovascular Health Study. AB - OBJECTIVES: The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults. BACKGROUND: HF incurs high morbidity, mortality, and health care costs among adults >=65 years of age, which is the most rapidly growing segment of the U.S. METHODS: We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity. RESULTS: No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26% and 22% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; leisure activity >=845 kcal/week vs. <845 kcal/week; HR: 0.78; 95% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m(2), and not smoking were also independently associated with a lower risk of HF. Participants with >=4 healthy lifestyle factors had a 45% (HR: 0.55; 95% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed. CONCLUSIONS: Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF. PMID- 26160367 TI - Primary Prevention of Heart Failure in Older Adults. PMID- 26160368 TI - Racial Differences in Heart Failure Outcomes: Evidence From the Tele-HF Trial (Telemonitoring to Improve Heart Failure Outcomes). AB - OBJECTIVES: The purpose of this study was to determine whether there are racial differences in patient-reported health status as well as mortality and rehospitalization after hospitalization for heart failure (HF). BACKGROUND: Little is known about whether racial differences exist in patient-reported outcomes after HF hospitalization. METHODS: We analyzed data from 1,427 patients (636 non-Hispanic African Americans [45%]; 791 non-Hispanic whites [55%]) enrolled in the Tele-HF (Telemonitoring to Improve Heart Failure Outcomes) trial. Health status was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and then at 3 and 6 months. Generalized linear mixed models and propensity score methods were used to adjust for clustering within sites and differences between races. RESULTS: Although black patients reported better adjusted health status at baseline (black vs. white difference in KCCQ summary scores was 6.22; 95% confidence interval [CI]: 2.98 to 9.46; p < 0.001), after adjusting for patient demographics, comorbidities, clinical laboratory values, and baseline KCCQ score, we detected no significant racial differences in patient reported health status at 3 months (black vs. white difference in KCCQ score: 2.28; 95% CI: -0.84 to 5.41; p = 0.15) or 6 months (black vs. white difference in KCCQ score: 1.91; 95% CI: -1.31 to 5.13; p = 0.24). CONCLUSIONS: Compared with white patients, black patients with HF had better patient-reported health status shortly after HF admission but not at 3 or 6 months. Our study failed to show that black patients were disadvantaged with regard to health status after HF hospitalization. (Tele-HF: Yale Heart Failure Telemonitoring Study; NCT00303212). PMID- 26160369 TI - Are Hospitalizations for Heart Failure the Great Equalizer? PMID- 26160372 TI - Why We Respect Randomized Controlled Clinical Trials in Heart Failure. PMID- 26160371 TI - Multiple Chronic Conditions and Heart Failure: Overlooking the Obvious? PMID- 26160370 TI - Burden of Comorbidities and Functional and Cognitive Impairments in Elderly Patients at the Initial Diagnosis of Heart Failure and Their Impact on Total Mortality: The Cardiovascular Health Study. AB - OBJECTIVES: The purpose of this study was to determine the prevalence of clinically relevant comorbidities and measures of physical and cognitive impairment in elderly persons with incident heart failure (HF). BACKGROUND: Comorbidities and functional and cognitive impairments are common in the elderly and often associated with greater mortality risk. METHODS: We examined the prevalence of 9 comorbidities and 4 measures of functional and cognitive impairments in 558 participants from the Cardiovascular Health Study who developed incident HF between 1990 and 2002. Participants were followed prospectively until mid-2008 to determine their mortality risk. RESULTS: Mean age of participants was 79.2 +/- 6.3 years with 52% being men. Sixty percent of participants had >=3 comorbidities, and only 2.5% had none. Twenty-two percent and 44% of participants had >=1 activity of daily living (ADL) and >=1 instrumental activity of daily living (IADL) impaired respectively. Seventeen percent of participants had cognitive impairment (modified mini-mental state exam score <80, scores range between 0 and 100). During follow up, 504 participants died, with 1-, 5-, and 10-year mortality rates of 19%, 56%, and 83%, respectively. In a multivariable-adjusted model, the following were significantly associated with greater total mortality risk: diabetes mellitus (hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.33 to 2.03), chronic kidney disease (HR: 1.32; 95% CI: 1.07 to 1.62 for moderate disease; HR: 3.00; 95% CI: 1.82 to 4.95 for severe), cerebrovascular disease (HR: 1.53; 95% CI: 1.22 to 1.92), depression (HR: 1.44; 95% CI: 1.09 to 1.90), functional impairment (HR: 1.30; 95% CI: 1.04 to 1.63 for 1 IADL impaired; HR: 1.49; 95% CI: 1.07 to 2.04 for >=2 IADL impaired), and cognitive impairment (HR: 1.33; 95% CI: 1.02 to 1.73). Other comorbidities (hypertension, coronary heart disease, peripheral arterial disease, atrial fibrillation, and obstructive airway disease) and measures of functional impairments (ADLs and 15-ft walk time) were not associated with mortality. CONCLUSIONS: Elderly patients with incident HF have a high burden of comorbidities and functional and cognitive impairments. Some of these conditions are associated with greater mortality risk. PMID- 26160373 TI - A new ultrasonic-assisted cloud-point-extraction procedure for pre-concentration and determination of ultra-trace levels of copper in selected beverages and foods by flame atomic absorption spectrometry. AB - A new ultrasonic-assisted cloud-point-extraction (UA-CPE) method was developed for the pre-concentration of Cu(II) in selected beverage and food samples prior to flame atomic absorption spectrometric (FAAS) analysis. For this purpose, Safranin T was used as an ion-pairing reagent based on charge transfer in the presence of oxalate as the primary chelating agent at pH 10. Non-ionic surfactant, poly(ethyleneglycol-mono-p-nonylphenylether) (PONPE 7.5) was used as an extracting agent in the presence of NH4Cl as the salting out agent. The variables affecting UA-CPE efficiency were optimised in detail. The linear range for Cu(II) at pH 10 was 0.02-70 ug l(-)(1) with a very low detection limit of 6.10 ng l(-)(1), while the linear range for Cu(I) at pH 8.5 was 0.08-125 ug l( )(1) with a detection limit of 24.4 ng l(-)(1). The relative standard deviation (RSD %) was in the range of 2.15-4.80% (n = 5). The method was successfully applied to the quantification of Cu(II), Cu(I) and total Cu in selected beverage and food samples. The accuracy of the developed method was demonstrated by the analysis of two standard reference materials (SRMs) as well as recoveries of spiked samples. PMID- 26160374 TI - Syndecan-4 Promotes Epithelial Tumor Cells Spreading and Regulates the Turnover of PKCalpha Activity under Mechanical Stimulation on the Elastomeric Substrates. AB - BACKGROUND: Heparan sulfate proteoglycans (HSPGs) at the cell surface play an important role in cell adhesion, spreading, formation of focal adhesion complexes (FACs), and sensing mechanical stress. Syndecans are members of the HSPGs family and are highly expressed in various tumor cells. Syndecan-4 (SDC4) is a unique member of syndecans that activates protein kinase C alpha (PKCalpha). However, syndecan-4 in tumor cells development is not clear when receiving mechanical stress. Aims: Here we investigate the role of syndecan-4 in tumor cells spreading and its downstream kinases under mechanical stimulation. METHODS: Epithelial tumor cells were seeded onto elastomeric polydimethylsiloxane (PDMS) membranes coated with poly-L-lysine (Pl), fibronectin (Fn), or anti-SDC4 antibody and stretched with a modified pressure-driven cell-stretching (PreCS) device. RESULTS: When cells received mechanical stimulation, engagement of syndecan-4 promoted the phosphorylation of focal adhesion kinase (FAK) at tyrosine 397 and PKCalpha at serine 657. Furthermore, we analyzed the cell contractility marker myosin light chain 2 (MLC2) in 30 min time courses. The levels of phosphorylated MLC2 at serine19 were augmented through ligations of syndecan-4 but not integrin binding motif (RGD) at 10 min mechanical stimulation and were suppressed at 30 min and this phenomenon was associated with the activity of PKCalpha. CONCLUSION: Our data demonstrate that syndecan-4 is essential for transmitting the mechanotransduction signals via activation of PKCalpha and is important for tumor cells spreading, assembly of actin cytoskeleton and cell contractility. PMID- 26160375 TI - QUANTUM OPTICS. Universal linear optics. AB - Linear optics underpins fundamental tests of quantum mechanics and quantum technologies. We demonstrate a single reprogrammable optical circuit that is sufficient to implement all possible linear optical protocols up to the size of that circuit. Our six-mode universal system consists of a cascade of 15 Mach Zehnder interferometers with 30 thermo-optic phase shifters integrated into a single photonic chip that is electrically and optically interfaced for arbitrary setting of all phase shifters, input of up to six photons, and their measurement with a 12-single-photon detector system. We programmed this system to implement heralded quantum logic and entangling gates, boson sampling with verification tests, and six-dimensional complex Hadamards. We implemented 100 Haar random unitaries with an average fidelity of 0.999 +/- 0.001. Our system can be rapidly reprogrammed to implement these and any other linear optical protocol, pointing the way to applications across fundamental science and quantum technologies. PMID- 26160377 TI - ROCK PHYSICS. Rock physics of fibrous rocks akin to Roman concrete explains uplifts at Campi Flegrei Caldera. AB - Uplifts in the Campi Flegrei caldera reach values unsurpassed anywhere in the world (~2 meters). Despite the marked deformation, the release of strain appears delayed. The rock physics analysis of well cores highlights the presence of two horizons, above and below the seismogenic area, underlying a coupled process. The basement is a calc-silicate rock housing hydrothermal decarbonation reactions, which provide lime-rich fluids. The caprock above the seismogenic area has a pozzolanic composition and a fibril-rich matrix that results from lime-pozzolanic reactions. These findings provide evidence for a natural process reflecting that characterizing the cementitious pastes in modern and Roman concrete. The formation of fibrous minerals by intertwining filaments confers shear and tensile strength to the caprock, contributing to its ductility and increased resistance to fracture. PMID- 26160378 TI - QUANTUM INFORMATION. Coherent coupling between a ferromagnetic magnon and a superconducting qubit. AB - Rigidity of an ordered phase in condensed matter results in collective excitation modes spatially extending to macroscopic dimensions. A magnon is a quantum of such collective excitation modes in ordered spin systems. Here, we demonstrate the coherent coupling between a single-magnon excitation in a millimeter-sized ferromagnetic sphere and a superconducting qubit, with the interaction mediated by the virtual photon excitation in a microwave cavity. We obtain the coupling strength far exceeding the damping rates, thus bringing the hybrid system into the strong coupling regime. Furthermore, we use a parametric drive to realize a tunable magnon-qubit coupling scheme. Our approach provides a versatile tool for quantum control and measurement of the magnon excitations and may lead to advances in quantum information processing. PMID- 26160379 TI - GLOBAL WARMING. Recent hiatus caused by decadal shift in Indo-Pacific heating. AB - Recent modeling studies have proposed different scenarios to explain the slowdown in surface temperature warming in the most recent decade. Some of these studies seem to support the idea of internal variability and/or rearrangement of heat between the surface and the ocean interior. Others suggest that radiative forcing might also play a role. Our examination of observational data over the past two decades shows some significant differences when compared to model results from reanalyses and provides the most definitive explanation of how the heat was redistributed. We find that cooling in the top 100-meter layer of the Pacific Ocean was mainly compensated for by warming in the 100- to 300-meter layer of the Indian and Pacific Oceans in the past decade since 2003. PMID- 26160376 TI - IMMUNODEFICIENCIES. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. AB - Human inborn errors of immunity mediated by the cytokines interleukin-17A and interleukin-17F (IL-17A/F) underlie mucocutaneous candidiasis, whereas inborn errors of interferon-gamma (IFN-gamma) immunity underlie mycobacterial disease. We report the discovery of bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional RORgamma and RORgammaT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORgamma- and RORgammaT-deficient individuals also displayed an impaired IFN gamma response to Mycobacterium. This principally reflected profoundly defective IFN-gamma production by circulating gammadelta T cells and CD4(+)CCR6(+)CXCR3(+) alphabeta T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORgamma, RORgammaT, or both. PMID- 26160380 TI - MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORgammat+ T cells. AB - Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (T(H)17) cells and regulatory T cells (T(regs)) in the intestine. Here, we report that microbiota-induced T(regs) express the nuclear hormone receptor RORgammat and differentiate along a pathway that also leads to T(H)17 cells. In the absence of RORgammat(+) T(regs), T(H)2-driven defense against helminths is more efficient, whereas T(H)2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORgammat(+) T(regs) and T(H)17 cells and acts as a key factor in balancing immune responses at mucosal surfaces. PMID- 26160382 TI - Army suicide attempts are most likely among enlisted soldiers on first tour of duty and female soldiers, US study finds. PMID- 26160381 TI - Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD. AB - OBJECTIVE: In IBD, interleukin-23 (IL-23) and its receptor (IL-23R) are implicated in disease initiation and progression. Novel insight into which cells produce IL-23 at the site of inflammation at an early stage of IBD will promote the development of new tools for diagnosis, treatment and patient monitoring. We examined the cellular source of IL-23 in colon tissue of untreated newly diagnosed paediatric patients with IBD. DESIGN: Colon tissues from IBD and non IBD patients were analysed by quantitative real-time PCR (qPCR), immunofluorescence confocal microscopy and flow cytometry after appropriate sample preparation. Blood samples from IBD and non-IBD patients and healthy controls were analysed using flow cytometry and qPCR. RESULTS: We discovered that tissue-infiltrating neutrophils were the main source of IL-23 in the colon of paediatric patients with IBD, while IL-23(+) human leucocyte antigen-DR(+) or IL 23(+)CD14(+) cells were scarce or non-detectable, respectively. The colonic IL 23(+) neutrophils expressed C-X-C motif (CXC)R1 and CXCR2, receptors for the CXC ligand 8 (CXCL8) chemokine family, and a corresponding CXCR1(+)CXCR2(+)IL 23(+)subpopulation of neutrophils was also identified in the blood of both patients with IBD and healthy individuals. However, CXCL8-family chemokines were only elevated in colon tissue from patients with IBD. CONCLUSIONS: This study provides the first evidence of CXCR1(+)CXCR2(+)IL-23-producing neutrophils that infiltrate and accumulate in inflamed colon tissue of patients with IBD. Thus, this novel source of IL-23 may play a key role in disease progression and will be important to take into consideration in the development of future strategies to monitor, treat and prevent IBD. PMID- 26160383 TI - Intraoperative navigation for single-splint two-jaw orthognathic surgery: From model to actual surgery. AB - OBJECTIVE: This study reported an intraoperative navigation system for single splint two-jaw orthognathic surgery, and assessed the accuracy of transferring the computer assisted surgical simulation. METHODS: A skull model was used for validation, and twenty patients receiving such procedure were enrolled. The procedure contained five phases, including virtual surgery on three-dimensional images, fabrication of surgical positioning guides, preparation of registration and validation landmarks, confirmation of bony position during surgery, and postoperative assessment. Target registration error (TRE) and differences between simulation (T0) and postoperative images (T1) were measured from landmarks to Frankfort horizontal plane (FHP), mid-sagittal plane (MSP), and coronal plane (COP). RESULTS: For the model experiment, mean TRE was lowest using the hard tissue landmarks (0.60 +/- 0.27 mm), and the mean difference (T1-T0) was less than 1 mm to all three planes. For the patients, mean TRE was 1.07 +/- 0.18 mm from the hard tissue landmarks. The mean difference was 0.96. +/- 0.60 mm from MSP, 1.39 +/- 1.11 mm from FHP, and 2.12 +/- 1.82 mm from COP. The differences were not significant. Both surgeons and patients were satisfied with the surgical outcome. CONCLUSION: This study showed that the navigation system had acceptable accuracy and was useful for the two-jaw orthognathic surgery using single-splint method. PMID- 26160385 TI - Hind- and Midfoot Motion After Ankle Arthrodesis. AB - BACKGROUND: After ankle arthrodesis (AA), compensatory increased range of motion in adjacent joints might lead to increased osteoarthritis. Evaluation of patient reported outcomes after AA with validated questionnaires is rare. Likewise, reliable radiographic analysis of the position of the AA, expected to influence the range of motion of the hind- and midfoot, is lacking. Therefore, the current study was performed. METHODS: Seventeen patients with unilateral AA were included. Sagittal hind- and midfoot range of motion was measured radiographically. The position of the AA in the sagittal and coronal planes and osteoarthritis of adjacent joints were also evaluated radiographically. Measurements were compared to the contralateral side. Patient-reported outcomes via validated questionnaires were compared to a control group (n = 18). RESULTS: Average follow-up was 3.5 years. Mean combined hind- and midfoot sagittal range of motion after AA equaled that of the contralateral side (20.8 vs. 21.0 degrees; P = .93). The tibiotalar angle after AA equaled that of the contralateral side (107 vs. 107 degrees; P = .86). The talus was translated posteriorly after AA (T T ratio 0.45 vs. 0.34; P < .001). Low intraclass correlation coefficients (ICC) precluded reliable evaluation of the coronal position of the hindfoot (ICC, 0.07 and -0.34) and osteoarthritis in adjacent joints (ICC range, 0-0.54). SF-36 physical health scores after AA are lower as compared with those of controls (50 vs. 56; P = .01). Scores on the Foot and Ankle Outcome Score and Ankle Osteoarthritis Scale were also significantly lower. Patient satisfaction with AA was high (average visual analog scale score, 83). CONCLUSION: No increased sagittal range of motion in the hind- and midfoot after AA was found at 3.5 years of follow-up as compared with the contralateral side. Tibiotalar angles were equal. The talus was translated posteriorly. The hindfoot alignment view was not suitable to analyze the position of the hindfoot. Low ICC of the Kellgren and Lawrence scale precluded evaluation of osteoarthritis of adjacent joints. Patients scored lower than controls on self-reported outcome questionnaires but were satisfied with the result of AA. PMID- 26160384 TI - Identifying avian malaria vectors: sampling methods influence outcomes. AB - BACKGROUND: The role of vectors in the transmission of avian malaria parasites is currently understudied. Many studies that investigate parasite-vector relationships use limited trapping techniques and/or identify potential competent vectors in the field in such ways that cannot distinguish between an infected or infectious vector. Without the use of multiple trapping techniques that address the specific biology of diverse mosquito species, and without looking at the infection status of individual mosquitoes, it is not possible to make dependable conclusions on the role of mosquitoes in the transmission of avian malaria parasites. METHODS: We conducted two years of mosquito collections at a riparian preserve in California where a wide diversity of species were collected with multiple trap types. We hypothesized that competent mosquito species can influence the distribution and diversity of avian malaria parasites by acting as a compatibility filter for specific Plasmodium species. To determine the infection status of all individual mosquitoes for Plasmodium species/lineages, amplification within the cytochrome b gene was carried out on over 3000 individual mosquito thoraxes, and for those that tested positive we then repeated the same process for abdomens and salivary glands. RESULTS: Our data show heterogeneity in the transmissibility of Plasmodium among ornithophillic mosquito species. More specifically, Culex stigmatosoma appears to not be a vector of Plasmodium homopolare, a parasite that is prevalent in the avian population, but is a vector of multiple other Plasmodium species/lineages. CONCLUSIONS: Our results suggest that conclusions made on the role of vectors from studies that do not use different mosquito trapping methods should be re-evaluated with caution, as we documented the potential for trapping biases, which may cause studies to miss important roles of specific mosquito species in the transmission of avian malaria. Moreover, we document heterogeneity in the transmission of Plasmodium spp. by mosquitoes can influence Plasmodium diversity and prevalence in specific locations to Plasmodium-vector incompatibilities. PMID- 26160386 TI - Algorithm for Severe Hallux Valgus Associated With Metatarsus Adductus. AB - BACKGROUND: Radiographic angles, such as the intermetatarsal angle, hallux valgus angle, and distal metatarsal articular angle, are commonly used to help guide operative planning for soft tissue and osseous treatment options for hallux valgus. Hallux valgus treatment in the setting of associated metatarsus adductus is less common and not well described. The presence of metatarsus adductus reduces the gap between the first and second metatarsals. Consequently, it complicates the measurement of the first-second intermetatarsal angle and can limit the area available for transposition of the first metatarsal head. A compensatory pronation is also created, which must be compensated for. We present 4 cases of patients that had hallux valgus with severe metatarsus adductus treated operatively, as well as a treatment algorithm. METHODS: For concomitant correction of both the metatarsus adductus and the hallux valgus, a thorough surgical treatment algorithm was implemented to address the hallux, lesser toe deformities, and pes planus deformity. Postoperatively, the patients were kept non-weight bearing for 6 weeks, followed by gradual weight bearing in a protective boot. Physical therapy was instituted at the start of weight bearing to encourage a return to activities of daily living. RESULTS: At follow-up, patients reported significant relief of their pain symptoms with a narrower and improved appearance of the foot. No recurrence was noted. One patient used a medial arch support but was otherwise symptom free. Radiographic measurements improved on postoperative radiographs. CONCLUSIONS: For the treatment of hallux valgus with metatarsus adductus, the second and third metatarsals may need to be addressed for the first metatarsal to be laterally transposed adequately. Overall, this comprehensive approach addresses the hindfoot, midfoot, and forefoot for patients with hallux valgus associated with metatarsus adductus, with successful results. PMID- 26160387 TI - Repair of Acute Superficial Deltoid Complex Avulsion During Ankle Fracture Fixation in National Football League Players. AB - BACKGROUND: Infolding and retraction of an avulsed deltoid complex after ankle fracture can be a source of persistent increased medial clear space, malreduction, and postoperative pain and medial instability. The purpose of this descriptive case series was to analyze the preliminary outcomes of acute superficial deltoid complex avulsion repair during ankle fracture fixation in a cohort of National Football League (NFL) players. We found that there is often complete avulsion of the superficial deltoid complex off the proximal aspect of the medial malleolus during high-energy ankle fractures in athletes. METHODS: Between 2004 and 2014, the cases of 14 NFL players who underwent ankle fracture fixation with open deltoid complex repair were reviewed. Patients with chronic deltoid ligament injuries or ankle fractures more than 2 months old were excluded. Average age for all patients was 25 years and body mass index 34.4. Player positions included 1 wide receiver, 1 tight end, 1 safety, 1 running back, 1 linebacker, and 9 offensive linemen. Average time from injury to surgery was 7.5 days. Surgical treatment for all patients consisted of ankle arthroscopy and debridement, followed by fibula fixation with plate and screws, syndesmotic fixation with suture-button devices, and open deltoid complex repair with suture anchors. Patient demographics were recorded with position played, time from injury to surgery, games played before and after surgery, ability to return to play, and postoperative complications. Return to play was defined as the ability to successfully participate in at least 1 full regular-season NFL game after surgery. RESULTS: All NFL players were able to return to running and cutting maneuvers by 6 months after surgery. There were no significant differences in playing experience before surgery versus after surgery. Average playing experience before surgery was 3.3 seasons, 39 games played, and 22 games started. Average playing experience after surgery was 1.6 seasons, 16 games played, and 15 games started. Return to play was 86% for all players. There were no intraoperative or postoperative complications noted, and no players had clinical evidence of medial pain or instability at final follow-up with radiographic maintenance of anatomic mortise alignment. CONCLUSION: Superficial deltoid complex avulsion during high-energy ankle fractures in athletes is a distinct injury pattern that should be recognized and may benefit from primary open repair. The majority of NFL players treated surgically for this injury pattern are able to return to play after surgery with no reported complications or persistent medial ankle pain or instability. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 26160388 TI - Outcomes of the Bridle Procedure for the Treatment of Foot Drop. AB - BACKGROUND: The purpose of this study was to determine the clinical outcomes and objective measures of function that can be expected for patients following the Bridle procedure (modification of the posterior tibial tendon transfer) for the treatment of foot drop. METHODS: Nineteen patients treated with a Bridle procedure and 10 matched controls were evaluated. The Bridle group had preoperative and 2-year postoperative radiographic foot alignment measurements and completion of the Foot and Ankle Ability Measure. At follow-up, both groups were tested for standing balance (star excursion test) and for ankle plantarflexion and dorsiflexion isokinetic strength, and the American Orthopaedic Foot & Ankle Society and Stanmore outcome measures were collected only on the Bridle patients. RESULTS: There was no change in radiographic foot alignment from pre- to postoperative measurement. Foot and Ankle Ability Measure subscales of activities of daily living and sport, American Orthopaedic Foot & Ankle Society, and Stanmore scores were all reduced in Bridle patients as compared with controls. Single-limb standing-balance reaching distance in the anterolateral and posterolateral directions were reduced in Bridle participants as compared with controls (P < .03). Isokinetic ankle dorsiflexion and plantarflexion strength was lower in Bridle participants (2 +/- 4 ft.lb, 44 +/- 16 ft.lb) as compared with controls (18 +/- 13 ft.lb, 65 +/- 27 ft.lb, P < .02, respectively). All Bridle participants reported excellent to good outcomes and would repeat the operation. No patient wore an ankle-foot orthosis for everyday activities. CONCLUSION: The Bridle procedure was a successful surgery that did not restore normal strength and balance to the foot and ankle but allowed individuals with foot drop and a functional tibialis posterior muscle to have significantly improved outcomes and discontinue the use of an ankle-foot orthosis. In addition, there was no indication that loss of the normal function of the tibialis posterior muscle resulted in change in foot alignment 2 years after surgery. LEVEL OF EVIDENCE: Level III, retrospective comparative series. PMID- 26160389 TI - Celecoxib and Ibuprofen Restore the ATP Content and the Gluconeogenesis Activity in the Liver of Walker-256 Tumor-Bearing Rats. AB - BACKGROUND/AIMS: The main purpose of this study was to investigate the effects of celecoxib and ibuprofen, both non-steroidal anti-inflammatory drugs (NSAIDs), on the decreased gluconeogenesis observed in liver of Walker-256 tumor-bearing rats. METHODS: Celecoxib and ibuprofen (both at 25 mg/Kg) were orally administered for 12 days, beginning on the same day when the rats were inoculated with Walker-256 tumor cells. RESULTS: Celecoxib and ibuprofen treatment reversed the reduced production of glucose, pyruvate, lactate and urea from alanine as well as the reduced production of glucose from pyruvate and lactate in perfused liver from tumor-bearing rats. Besides, celecoxib and ibuprofen treatment restored the decreased ATP content, increased triacylglycerol levels and reduced mRNA expression of carnitine palmitoyl transferase 1 (CPT1), while ibuprofen treatment restored the reduced mRNA expression of peroxisome proliferator-activated receptor alpha (PPARalpha) in the liver of tumor-bearing rats. Both treatments tended to decrease TNFalpha, IL6 and IL10 in the liver of tumor-bearing rats. Finally, the treatment with celecoxib, but not with ibuprofen, reduced the growth of Walker-256 tumor. CONCLUSION: Celecoxib and ibuprofen restored the decreased gluconeogenesis in the liver of Walker-256 tumor-bearing rats. These effects did not involve changes in tumor growth and probably occurred by anti-inflammatory properties of these NSAIDs, which increased expression of genes associated with fatty acid oxidation (PPARalpha and CPT1) and consequently the ATP production, normalizing the energy status in the liver of tumor-bearing rats. PMID- 26160390 TI - Antimicrobial activities of endophytic fungi obtained from the arid zone invasive plant Opuntia dillenii and the isolation of equisetin, from endophytic Fusarium sp. AB - BACKGROUND: Opuntia dillenii is an invasive plant well established in the harsh South-Eastern arid zone of Sri Lanka. Evidence suggests it is likely that the endophytic fungal populations of O. dillenii assist the host in overcoming biotic and abiotic stress by producing biologically active metabolites. With this in mind there is potential to discover novel natural products with useful biological activities from this hitherto poorly investigated source. Consequently, an investigation of the antimicrobial activities of the endophytes of O. dillenii, that occupies a unique ecological niche, may well provide useful leads in the discovery of new pharmaceuticals. METHODS: Endophytic fungi were isolated from the surface sterilized cladodes and flowers of O. dillenii using several nutrient media and the antimicrobial activities were evaluated against three Gram-positive and two Gram-negative bacteria and Candida albicans. The two most bioactive fungi were identified by colony morphology and DNA sequencing. The secondary metabolite of the endophyte Fusarium sp. exhibiting the best activity was isolated via bioassay guided chromatography. The chemical structure was elucidated from the ESIMS and NMR spectroscopic data obtained for the active metabolite. The minimum inhibitory concentrations (MICs) of the active compound were determined. RESULTS: Eight endophytic fungi were isolated from O. dillenii and all except one showed antibacterial activities against at least one of the test bacteria. All extracts were inactive against C. albicans. The most bioactive fungus was identified as Fusarium sp. and the second most active as Aspergillus niger. The structure of the major antibacterial compound of the Fusarium sp. was shown to be the tetramic acid derivative, equisetin. The MIC's for equisetin were 8 MUg mL(-1) against Bacillus subtilis, 16 MUg mL(-1) against Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus (MRSA). CONCLUSIONS: O. dillenii, harbors several endophytic fungi capable of producing antimicrobial substances with selective antibacterial properties. By producing biologically active secondary metabolites, such as equisetin isolated from the endophytic Fusarium sp., the endophytic fungal population may be assisting the host to successfully withstand stressful environmental conditions. Further investigations on the secondary metabolites produced by these endophytes may provide additional drug leads. PMID- 26160392 TI - Recent novel applications of levansucrases. AB - Levansucrase catalyzes three distinct reactions depending on the fructosyl acceptor molecule, including polymerization, transfructosylation, and hydrolysis. As a key biocatalyst in the synthesis of levan and levan-type fructooligosaccharides, levansucrase has been widely and intensively studied. Due to the promising physiological effects of levan and levan-type fructooligosaccharides, they exhibit great potential in food and pharmaceutical industries. Another important point that attracts much attention is the wide substrate specificity of levansucrase toward monosaccharides, disaccharides, and aromatic and alkyl alcohols, producing diverse sucrose analogues, hetero oligosaccharides (especially lactosucrose), and interesting fructosides. The present article summarizes and discusses the recent applications of microbial levansucrase in detail. PMID- 26160391 TI - Versatile vector suite for the extracytoplasmic production and purification of heterologous His-tagged proteins in Lactococcus lactis. AB - Recent studies have shown that the Gram-positive bacterium Lactococcus lactis can be exploited for the expression of heterologous proteins; however, a versatile set of vectors suitable for inducible extracellular protein production and subsequent purification of the expressed proteins by immobilized metal affinity chromatography was so far lacking. Here we describe three novel vectors that, respectively, facilitate the nisin-inducible production of N- or C-terminally hexa-histidine (His6)-tagged proteins in L. lactis. One of these vectors also encodes a tobacco etch virus (TEV) protease cleavage site allowing removal of the N-terminal His6-tag from expressed proteins. Successful application of the developed vectors for protein expression, purification and/or functional studies is exemplified with six different cell wall-bound or secreted proteins from Staphylococcus aureus. The results show that secretory production of S. aureus proteins is affected by the position, N- or C-terminal, of the His6-tag. This seems to be due to an influence of the His6-tag on protein stability. Intriguingly, the S. aureus IsdB protein, which is phosphorylated in S. aureus, was also found to be phosphorylated when heterologously produced in L. lactis, albeit not on the same Tyr residue. This implies that this particular post translational protein modification is to some extent conserved in S. aureus and L. lactis. Altogether, we are confident that the present vector set combined with the L. lactis expression host has the potential to become a very useful tool in optimization of the expression, purification and functional analysis of extracytoplasmic bacterial proteins. PMID- 26160394 TI - A transversal approach for patch-based label fusion via matrix completion. AB - Recently, multi-atlas patch-based label fusion has received an increasing interest in the medical image segmentation field. After warping the anatomical labels from the atlas images to the target image by registration, label fusion is the key step to determine the latent label for each target image point. Two popular types of patch-based label fusion approaches are (1) reconstruction-based approaches that compute the target labels as a weighted average of atlas labels, where the weights are derived by reconstructing the target image patch using the atlas image patches; and (2) classification-based approaches that determine the target label as a mapping of the target image patch, where the mapping function is often learned using the atlas image patches and their corresponding labels. Both approaches have their advantages and limitations. In this paper, we propose a novel patch-based label fusion method to combine the above two types of approaches via matrix completion (and hence, we call it transversal). As we will show, our method overcomes the individual limitations of both reconstruction based and classification-based approaches. Since the labeling confidences may vary across the target image points, we further propose a sequential labeling framework that first labels the highly confident points and then gradually labels more challenging points in an iterative manner, guided by the label information determined in the previous iterations. We demonstrate the performance of our novel label fusion method in segmenting the hippocampus in the ADNI dataset, subcortical and limbic structures in the LONI dataset, and mid-brain structures in the SATA dataset. We achieve more accurate segmentation results than both reconstruction-based and classification-based approaches. Our label fusion method is also ranked 1st in the online SATA Multi-Atlas Segmentation Challenge. PMID- 26160396 TI - Pseudo-aneurism with systolic compressive effect on the left coronary artery: a rare complication after infective endocarditis. PMID- 26160393 TI - Variability in laboratory parameters used for management of Cushing's syndrome. AB - The progress in assay methodology, from the use of radioactive tracers to chemiluminescent signals, from competitive to chromatographic techniques and from serum or urine to saliva has considerably impacted on hormonal measurements. The clinician now may choose among multiple tests but the inherent variability in cortisol and ACTH secretion, coupled to lack of harmonization among assay procedures and normal ranges mandates careful interpretation of any result. The present review will examine factors which affect interpretation of cortisol and ACTH measurements and their impact on tests used for management of Cushing's syndrome. PMID- 26160395 TI - The Right Ventricular Function After Left Ventricular Assist Device (RVF-LVAD) study: rationale and preliminary results. AB - AIMS: Despite improved outcomes and lower right ventricular failure (RVF) rates with continuous-flow left ventricular assist devices (LVADs), RVF still occurs in 20-40% of LVAD recipients and leads to worse clinical and patient-centred outcomes and higher utilization of healthcare resources. Preoperative quantification of RV function with echocardiography has only recently been considered for RVF prediction, and RV mechanics have not been prospectively evaluated. METHODS AND RESULTS: In this single-centre prospective cohort study, we plan to enroll a total of 120 LVAD candidates to evaluate standard and mechanics-based echocardiographic measures of RV function, obtained within 7 days of planned LVAD surgery, for prediction of (i) RVF within 90 days; (ii) quality of life (QoL) at 90 days; and (iii) RV function recovery at 90 days post-LVAD. Our primary hypothesis is that an RV echocardiographic score will predict RVF with clinically relevant discrimination (C >0.85) and positive and negative predictive values (>80%). Our secondary hypothesis is that the RV score will predict QoL and RV recovery by 90 days. We expect that RV mechanics will provide incremental prognostic information for these outcomes. The preliminary results of an interim analysis are encouraging. CONCLUSION: The results of this study may help improve LVAD outcomes and reduce resource utilization by facilitating shared decision-making and selection for LVAD implantation, provide insights into RV function recovery, and potentially inform reassessment of LVAD timing in patients at high risk for RVF. PMID- 26160397 TI - Feasibility of ultra-low contrast 64-slice computed tomography angiography before transcatheter aortic valve implantation: a real-world experience. AB - AIMS: To investigate the feasibility, image quality, and clinical implications of an ultra-low-dose contrast injection computed tomography angiography (CTA) protocol in patients scheduled for transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Images obtained with 64-slice CT were retrospectively evaluated in 162 TAVI candidates with a body mass index (BMI) of <=29 kg/m(2). A multiphasic, low iodine dose and BMI-adapted CM protocol was administered in all patients (BMI <22 kg/m(2): 40 mL; BMI 22-29 kg/m(2): 55 mL). All images were evaluated for image quality, vessel attenuation, and estimated radiation dose. The anatomy, diameters, perimeter, and area of the aortic annulus were assessed. Anatomy and diameters of peripheral vessels were also evaluated. Image quality of the aortic root and ilio-femoral vessels was diagnostic in all patients. Vascular attenuation was >200 HU at any vessel level. The mean diameters of the aortic annulus were 22 +/- 3 mm (range: 16-28 mm) * 26 +/- 3 mm (range: 20-33 mm); the mean perimeter was 77.0 +/- 7.1 mm. After CTA, a total of 137 patients (84.6%) underwent TAVI. Mean estimated radiation dose was 20.2 +/- 4.6 mSv. CONCLUSION: With our protocol, we achieved images of the aortic annulus and aorto-iliac anatomy of sufficient quality to allow patient selection and procedural planning for TAVI, with a substantial reduction of the amount of injected CM. PMID- 26160398 TI - Multiparametric relaxometry by cardiac magnetic resonance imaging in Takotsubo cardiomyopathy. PMID- 26160400 TI - Giant right coronary artery fistula to the coronary sinus: multimodal imaging. PMID- 26160399 TI - Device landing zone calcification and its impact on residual regurgitation after transcatheter aortic valve implantation with different devices. AB - AIMS: Calcification of the device landing zone is linked to paravalvular regurgitation after transcatheter aortic valve implantation (TAVI). The mechanisms remain incompletely understood and the performance of next-generation transcatheter heart valves (THV) has not been investigated. We evaluated the impact of calcification patterns on residual aortic regurgitation (AR) after TAVI with different THV in patients with severe aortic stenosis. METHODS AND RESULTS: TAVI was performed in 537 patients at two centres. Devices implanted were the Edwards Sapien XT (n = 254), Medtronic CoreValve (n = 123), JenaValve (n = 62), Medtronic Engager (n = 56), and Symetis Acurate (n = 42) prostheses. Calcification of the device landing zone was retrospectively assessed from contrast-enhanced multidetector computed tomography data and correlated with echocardiographic and clinical data. Calcium volumes of the aortic valve and left ventricular outflow tract were associated with residual AR: No AR, 604 mm(3) (inter-quartile range, IQR 349-916); trace AR, 639 mm(3) (IQR 368-948); mild AR, 710 mm(3) (IQR 412-2078); >=moderate AR, 1041 mm(3) (IQR 791-1417, P = 0.001). Device landing zone calcium, particularly if located in the left-ventricular outflow tract, and a low cover index were predictive of AR. Differences in the incidence of AR were observed with regard to THV type. Higher calcium volume was associated with the need for post-dilation (n = 134, median 852 [IQR 342-945] vs. 604 [IQR 542-1207] mm(3), P < 0.001). CONCLUSION: Calcification of the device landing zone, particularly if located inferior to the annulus, was independently associated with residual AR after TAVI with all evaluated THV; however, the incidence of paravalvular leakage differed significantly between the devices implanted. PMID- 26160401 TI - Disintegration of polyvinyl alcohol membrane covering atrial septal defect closure device. PMID- 26160402 TI - Left ventricular dyssynergy and dispersion as determinant factors of fatal ventricular arrhythmias in patients with mildly reduced ejection fraction. AB - AIMS: Current guidelines recommend implantation of prophylactic implantable cardioverter-defibrillators (ICD) in patients with left ventricular (LV) ejection fraction (EF) <35%. We explored the prognostic factors of fatal ventricular arrhythmias for heart failure (HF) patients with LVEF >=35%. METHODS AND RESULTS: We retrospectively studied 72 patients with LVEF of 52 +/- 12% (all >=35%) who had undergone ICD implantation. Heterogeneity of LV regional myocardial contraction was defined as standard deviation of peak strain (dyssynergy index) and time-to-peak strain (dispersion index) from 18 LV segments determined by speckle tracking. Fatal ventricular arrhythmias with appropriate ICD therapy occurred in 34 patients (47%) during a median follow-up of 17 months. Receiver operating characteristic curve analysis identified dispersion index >=101 ms and dyssynergy index >=6.1% as predictors of fatal ventricular arrhythmias (P = 0.004 and P = 0.0001, respectively). In addition, the combination of dispersion index >=101 ms and dyssynergy index >=6.1% was the most predictive of fatal ventricular arrhythmias with a sensitivity of 77%, specificity of 79%, and area under the curve of 0.795 (P < 0.0001). A sequential Cox model based on clinical and conventional echocardiographic variables including age, gender, HF aetiology, and LVEF (chi(2) = 4.8) was improved, but not statistically significant (chi(2) = 4.9; P = 0.82), by addition of global longitudinal strain, whereas improvement by the addition of the dispersion index (chi(2) = 8.9; P = 0.04) and further improvement by the addition of the dyssynergy index (chi(2) = 20.2; P < 0.005). CONCLUSION: Combined assessment of LV dyssynergy and dispersion can enhance predictive capability for fatal ventricular arrhythmias in patients with LVEF >=35% and may have potential for better management of such patients. PMID- 26160403 TI - Left and right ventricular systolic function impairment in type 1 diabetic young adults assessed by 2D speckle tracking echocardiography. AB - AIMS: Subclinical left ventricular (LV) and right ventricular (RV) systolic dysfunction has been proved in type 2 diabetes mellitus (DM). There is lack of uniform data on systolic myocardial function in type 1 DM. The aim of this study was to evaluate LV and RV function with 2D speckle tracking echocardiography (2D STE) in adult type 1 diabetic patients. METHODS AND RESULTS: Totally, 50 patients with type 1 DM and 50 control subjects in the same range of age were prospectively evaluated. The 2D STE assessment of LV longitudinal, radial, circumferential strain and RV free-wall longitudinal strain was performed. In diabetic group, left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left ventricular radial strain at basal level (LVRS-basal), and right ventricular free-wall global longitudinal strain (RVGLS) were significantly lower compared with the controls: LVGLS (-20.3 +/- 2.0% vs. -22.2 +/- 1.8%, P < 0.001), LVGCS (-21.1 +/- 2.5% vs. -22.2 +/- 2.4%, P < 0.05), LVRS-basal (50.5% +/- 11.5 vs. 57.1% +/-17.0, P < 0.05), and RVGLS (-30.1% +/- 3.5 vs. -32.7% +/- 3.9, P < 0.01). Multivariable logistic regression analysis showed that the only independent predictor of reduced LVGLS was low-density lipoprotein cholesterol [odds ratio 3.65 (95% confidence interval: 1.27-10.5), P = 0.014]. CONCLUSION: Type 1 DM is associated with subclinical LV systolic dysfunction and worse RV systolic function, which can be detected with 2D STE. PMID- 26160404 TI - Three-dimensional echocardiography-based analysis of right ventricular shape in pulmonary arterial hypertension. AB - AIMS: Right ventricular (RV) remodelling involves changes in size, function, and shape. Although three-dimensional echocardiography (3DE) allows imaging of RV morphology, regional RV shape analysis has not been evaluated using 3DE. We developed a technique to quantify RV shape and tested its ability to differentiate normal from pressure overloaded right ventricles. Methods Transthoracic 3DE RV images were acquired in 54 subjects, including 39 patients with pulmonary artery hypertension (PAH) and 15 normal controls (NL). 3D RV surfaces were reconstructed (TomTec) at end-diastole and end-systole (ED, ES) and processed using custom software to calculate mean curvature of the inflow and outflow tracts (RVIT, RVOT), apex, and body (both divided into free wall and septum). METHODS AND RESULTS: Septal segments (apical and body) in NLs were characterized by concavity (curvature < 0) in ED and slight convexity (curvature > 0) in ES. In PAH, however, the septum remained convex, bulging into the left ventricle throughout the cardiac cycle. In keeping with the 'bellows-like' action of RV contraction in the NL group, the body free wall transitioned from a convex surface at ED to a more flattened surface at ES, while the apex free wall progressed from a less convex surface at ED to a more convex surface at ES. In contrast, in PAH, both RV free-wall segments (apical and body) remained equally convex throughout the cardiac cycle. CONCLUSIONS: Curvature analysis using 3D echocardiography allows quantitative evaluation of RV remodelling, which could be used to track differential changes in regional RV shape, as a way to assess disease progression or regression. PMID- 26160405 TI - Association between elevated serum alanine aminotransferase and cardiometabolic risk factors in rural Chinese population: a cross-sectional study. AB - BACKGROUND: Elevated alanine aminotransferase (ALT) levels may be associated with metabolic syndrome and cardiovascular diseases. This study aimed to investigate the association between elevated ALT levels and cardiometabolic risk factors in a rural Chinese population. METHODS: This was a cross-sectional study conducted from July 2012 to August 2013, including 11,573 subjects (5,357 men and 6,216 women) aged >=35 years in rural areas of Liaoning Province. A physical examination was performed and metabolic indicators were examined under standard protocols. Subjects were divided into those with elevated ALT levels (>40U/L) and those with normal ALT levels (<=40U/L). RESULTS: Participants with elevated ALT levels had higher levels of almost all cardiometabolic risk factors than those with normal ALT levels. In individuals with elevated ALT levels, weight, height, waist circumference, and body mass index (BMI), which are indicators for general and abdominal obesity, were significantly higher (p < 0.001) than those in individuals with normal ALT levels. There was no significant difference in race, current smoking, or physical activity between the two groups. Other cardiometabolic risk factors, such as systolic blood pressure, diastolic blood pressure, and fasting plasma glucose, TC, TG, low-density lipoprotein cholesterol, and serum uric acid levels, were higher in participants with elevated ALT levels than in those with normal ALT levels. Logistic regression analysis showed that male sex, younger age, and the presence of high TC, high TG, and low high-density lipoprotein cholesterol levels, current smoking status, BMI >=25 kg/m(2), abdominal obesity, hyperuricemia, and HtgW phenotype were significantly (p < 0.05) associated with elevated ALT levels. Sex-related differences were also investigated. For men, hypertension (OR 1.33, 95 % CI 1.08 1.62), high TC levels (OR 1.63, 95 % CI 1.23-2.17), high TG levels (OR 1.62, 95 % CI 1.25-2.09), BMI >=25 kg/m(2) (OR 1.52, 95 % CI 1.07-2.18), and hyperuricemia (OR 1.92, 95 % CI 1.52-2.40) were significantly (p < 0.05) related to elevated serum ALT levels, but this was not observed in women. CONCLUSIONS: There are significant relationships of elevated ALT levels with cardiometabolic risk factors and several sex-related differences in rural Chinese. Elevated serum ALT levels are associated with a worse cardiac risk profile. PMID- 26160406 TI - Characterization and evolution of xylose isomerase screened from the bovine rumen metagenome in Saccharomyces cerevisiae. AB - The conversion of abundant levels of xylose in lignocellulosic materials into viable products would generate economic benefits. The heterologous expression of the xylose isomerase (XI) gene is considered a direct and effective strategy for establishing the xylose metabolic pathway in Saccharomyces cerevisiae. However, only limited sources of xylA are functionally expressed in S. cerevisiae and are capable of driving effective xylose consumption. In this study, Ru-xylA (where Ru represents the rumen), which was screened from the contents of the bovine rumen metagenomic library, was functionally expressed in S. cerevisiae, and the enzyme activity was 1.31 U mg(-1) protein. This is a new source of XI that can exhibit high activity levels in S. cerevisiae. The activity of this enzyme is comparable to those of the Piromyces sp. XI. Then, the Ru-XI activity was further improved through mutagenesis and growth-based screening in a centromeric plasmid. A variant containing two mutations (K11T/D220V) that exhibited a 68% increase in enzyme activity was isolated. Our work identified a new xylose isomerase that can be functionally expressed in S. cerevisiae and results in a higher XI enzyme activity through mutagenesis. PMID- 26160408 TI - Low intensity exercise does not impact cognitive function during exposure to normobaric hypoxia. AB - Exposure to hypoxia is associated with cognitive impairment, mediated by cerebral deoxygenation. This can be problematic for individuals who perform mental tasks at high altitude. Eight healthy men completed two experimental trials consisting of 5h of exposure to normobaric hypoxia (12.5% O2). In one of the experimental trials (Hypoxia) subjects remained resting in a seated position the entire 5h; in the other experimental trial (Hypoxia and Exercise) subjects rested 2h, cycled for 1h at constant wattage (workload equivalent to 50% of altitude adjusted VO2max), then rested the last 2h. Cerebral oxygenation was measured continuously via near-infrared spectroscopy and cognitive performance was assessed by Trail Making Test A and B. Cerebral oxygenation and cognitive performance both were impaired during exposure to hypoxia. In the Hypoxia and Exercise trial, subjects experienced further declinations in cerebral oxygenation without concomitant decreases in cognitive function. These data demonstrate that cognitive function declines during exposure to normobaric hypoxia and this decline is not exacerbated by low intensity exercise. PMID- 26160407 TI - HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation. AB - BACKGROUND: Human immunodeficiency virus type 2 (HIV-2) is often distinguished clinically by lower viral loads, reduced transmissibility, and longer asymptomatic periods than for human immunodeficiency virus type 1 (HIV-1). Differences in the mutation frequencies of HIV-1 and HIV-2 have been hypothesized to contribute to the attenuated progression of HIV-2 observed clinically. RESULTS: To address this hypothesis, we performed Illumina sequencing of multiple amplicons prepared from cells infected with HIV-1 or HIV-2, resulting in ~4.7 million read pairs and the identification of ~200,000 mutations after data processing. We observed that: (1) HIV-2 displayed significantly lower total mutation, substitution, and transition mutation frequencies than that of HIV-1, along with a mutation spectrum markedly less biased toward G-to-A transitions, (2) G-to-A hypermutation consistent with the activity of APOBEC3 proteins was observed for both HIV-1 and HIV-2 despite the presence of Vif, (3) G-to-A hypermutation was significantly higher for HIV-1 than for HIV-2, and (4) HIV-1 and HIV-2 total mutation frequencies were not significantly different in the absence of G-to-A hypermutants. CONCLUSIONS: Taken together, these data demonstrate that HIV-2 exhibits a distinct mutational spectrum and a lower mutation frequency relative to HIV-1. However, the observed differences were primarily due to reduced levels of G-to-A hypermutation for HIV-2. These findings suggest that HIV-2 may be less susceptible than HIV-1 to APOBEC3-mediated hypermutation, but that the fidelities of other mutational sources (such as reverse transcriptase) are relatively similar for HIV-1 and HIV-2. Overall, these data imply that differences in replication fidelity are likely not a major contributing factor to the unique clinical features of HIV-2 infection. PMID- 26160409 TI - The Medical Treatment of New-Onset Peripartum Cardiomyopathy: A Systematic Review of Prospective Studies. AB - BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare disorder with potentially fatal consequences, which occurs mainly in previously healthy women. The aetiology of PPCM remains unknown and various pathologic mechanisms have been proposed, including immune-mediated injuries and impaired response to oxidative stress and inflammatory cytokines. Several therapies have been studied, but few have been validated in a well-designed randomized controlled trial. METHODS: In the present study we sought to review the medical treatment intended for acute PPCM. To this end, we performed a systematic review of the literature of randomized and nonrandomized prospective clinical studies. RESULTS: We identified 2 randomized controlled trials that evaluated the dopamine agonist bromocriptine and the inotrope levosimendan, respectively, and 1 nonrandomized study that evaluated the nonselective phosphodiesterase inhibitor pentoxifylline. We reviewed the pathophysiological, pharmacological, and clinical properties for each treatment option identified. Bromocriptine and pentoxifylline both improved left ventricular systolic function and patient-oriented clinical end points and levosimendan did not improve mortality or echocardiographic findings of PPCM. CONCLUSIONS: In this review we identified bromocriptine and pentoxifylline, but not levosimendan, as potentially useful agents to improve left ventricle function and outcomes in PPCM. PMID- 26160410 TI - Tumor Necrosis Factor-Alpha and 8-Hydroxy-2'-Deoxyguanosine are Associated with Elevated Urinary Angiopoietin-2 Level in Type 2 Diabetic Patients with Albuminuria. AB - BACKGROUND/AIMS: We previously showed that urine and serum Angiopoietin-2 (Ang-2) levels increased significantly with the degree of albuminuria in diabetes patients, but the reasons remain unclear. Consequently we aimed to determine whether there was an association between Ang-2, inflammatory cytokines (TNF-alpha and IL-18) and reactive oxygen species (8-OHdG and SOD) in type 2 diabetes patients with albuminuria. METHODS: This retrospective study evaluated 113 patients with type 2 diabetes and normoalbuminuria, microalbuminuria, or macroalbuminuria and 30 healthy controls. Serum and urine TNF-alpha, IL-18 and 8 OHdG levels were measured by ELISA. Superoxide dismutase (SOD) activity was determined by spectrophotometry. RESULTS: Serum and urine TNF-alpha, IL-18 and 8 OHdG levels increased significantly with the degree of albuminuria, and were positively correlated with increased Ang-2. In contrast, SOD activity decreased with the degree of albuminuria and was negatively correlated with Ang-2. Multivariable linear regression analysis revealed that serum Ang-2 level was independently associated with serum levels of TNF-alpha (P<0.001), 8-OHdG (P=0.001), and IL-18 (P=0.003). Urinary Ang-2 level was independently associated with urinary TNF-alpha (P<0.001) and 8-OHdG (P=0.004) levels. CONCLUSION: TNF alpha and 8-OHdG are associated with elevated urinary Angiopoietin-2 levels in type 2 diabetic patients with albuminuria. PMID- 26160411 TI - Twelve lead electrocardiography after collapse. PMID- 26160412 TI - Evaluation of a combined glycomics and glycoproteomics approach for studying the major glycoproteins present in biofluids: Application to cerebrospinal fluid. AB - RATIONALE: Glycosylation is one of the most complex types of post-translational modifications of proteins. The alteration of glycans bound to proteins from cerebrospinal fluid (CSF) in relation to disorders of the central nervous system is a highly relevant subject, but only few studies have focused on the glycosylation of CSF proteins. METHODS: Reproducible profiles of CSF N-glycans were first obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry after permethylation. Tryptic glycopeptides from CSF proteins were also enriched by hydrophilic interaction, and the resulting extracts divided into two equal aliquots. A first aliquot was enzymatically deglycosylated and analyzed by nano-liquid chromatography/tandem mass spectrometry while the second one, containing intact enriched glycopeptides, was directly analyzed. Site specific data were obtained by combining the data from these three experiments. RESULTS: We describe the development of a versatile approach for obtaining site specific information on the N-glycosylation of CSF glycoproteins. Under these conditions, 124 N-glycopeptides representing 55 N-glycosites from 36 glycoproteins were tentatively identified. Special emphasis was placed on the analysis of glycoproteins/glycopeptides bearing 'brain-type' N-glycans, representing potential biologically relevant structures in the field of neurodegenerative disorders. Using our workflow, only a few proteins were shown to carry such particular glycan motifs. CONCLUSIONS: We developed an approach combining N-glycomics and N-glycoproteomics and underline its usefulness to study the site-specific glycosylation of major human CSF proteins. The final rather long-term objective is to combine these data with those from other omics approaches to delve deeper into the understanding of particular neurological disorders. PMID- 26160413 TI - Quantitative surface scanning by Direct Analysis in Real Time mass spectrometry. AB - RATIONALE: Only a few ambient ionization sources have been demonstrated to work quantitatively for surface scanning. A modification of the Direct Analysis in Real Time mass spectrometry (DART-MS) interface is needed to improve the precision during the scanning of a high-performance thin-layer chromatography (HPTLC) plate or any other surface or planar substrate, especially for quantitation without an internal standard correction. METHODS: The substrate movement relative to the ion source outlet and the mass spectrometer inlet was optimized to improve the desorption, ionization, and capture of analytes. The substrate carrier was mounted at an angled position, thus reducing collisions between the deflected gas stream and the inner transfer tube wall. A special transfer tube, whose edge was angled towards the substrate and allowed a narrow set-up of the ambient air gap, captured the deflected DART gas stream. RESULTS: For the repeated DART-MS scanning along five identical deposited bands of butyl-4 hydroxybenzoate a mean precision of 2.7% was obtained. A signal decay of 62% was observed after five scans. After HPTLC of methyl-4-hydroxybenzoate and butyl-4 hydroxybenzoate, mean determination coefficients of 0.9937 and 0.9906 were obtained for five calibrations on five plates, respectively. The mean recovery of two control standards was 94% with a mean repeatability of 9% (%RSD, n = 5) obtained on five different plates. CONCLUSIONS: The DART SVPA-3DS system remained compact and the access to the substrate was kept wide open despite the optimized scan lane (spatial resolution at full width at half maximum 0.8 mm, height 3 mm). The performance data showed that the quantitative surface scanning was improved as well as the desorption efficacy and detectability using this modified DART-MS interface. PMID- 26160414 TI - Screening of tricyclic quinazoline alkaloids in the alkaloidal fraction of Adhatoda beddomei and Adhatoda vasica leaves by high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry. AB - RATIONALE: Adhatoda beddomei and Adhatoda vasica are popular Ayurvedic medicinal plants in India, belonging to the family Acanthaceae. Tricyclic quinazoline alkaloids are found to be the most abundant in these plants which are responsible for broad-spectrum medicinal properties. This study aims to seek identification and characterization of those alkaloids based on their fragmentation patterns. METHODS: A method was developed to elucidate the main fragmentation pathways of tricyclic quinazoline alkaloids in positive ion mode using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of flight tandem mass spectrometry (HPLC/ESI-QTOF-MS/MS). Chromatographic separation was carried on a Supelco Discovery HS C18 column (15 cm * 4.6 mm, 3 um) with 0.1% formic acid aqueous solution and acetonitrile as a mobile phase. RESULTS: In full scan mass spectra, protonated molecules were observed for all the quinazoline alkaloids. Ring cleavages of the tricyclic quinazoline moiety were observed in MS(2) spectra and the characteristic ions provide valuable structural information of these alkaloids. Fragmentation pathways and fragment ion structures were proposed in two groups of quinazoline alkaloids. CONCLUSIONS: The established fragmentation patterns have been successfully used to identify 23 tricyclic quinazoline alkaloids in the alkaloidal fraction of A. beddomei and A. vasica. PMID- 26160415 TI - Competitive retro-cycloaddition reactions in heterocyclic fullerene bis-adducts ions: selective removal of the heterocyclic moieties. AB - RATIONALE: We have investigated the fragmentation reactions of ions from bis adducts containing isoxazolino-, pyrrolidino- and methanofullerene moieties. METHODS: The fragmentation reactions induced by collision-induced dissociation (CID) of ions generated under electrospray ionization (ESI) in positive and negative modes of detection using an ion-trap spectrometer have been investigated. RESULTS: The competitive retro-cycloaddition process between isoxazoline and pyrrolidine rings fused to [60]fullerene reveals that it is strongly dependent on the experimental negative or positive ESI experimental conditions. Thus, whereas retro-cycloaddition reaction is favored in the pyrrolidine ring under negative conditions, the protonation occurring on the nitrogen atom of the pyrrolidine ring under positive conditions precludes its retro-cycloaddition and, therefore, only the isoxazoline ring undergoes the retro cycloaddition process. The obtained experimental results are different from those reported when the reaction is carried out under thermal conditions. Competitive retro-cycloaddition reactions of isoxazolino- and methanofullerenes show that the heterocyclic ring undergoes cycloelimination, leaving the methanofullerene moiety unchanged. In this case, the same selectivity is observed under thermal and gas phase conditions. CONCLUSIONS: The observed selectivity in the heterocyclic removal in these [60]fullerene derivatives is reversed from negative conditions (radical anions) to positive conditions (protonated molecules). Moreover, the retro-cycloaddition reaction behaves differently under spectrometric and thermal conditions. PMID- 26160416 TI - Compound specific isotope analysis of hexachlorocyclohexane isomers: a method for source fingerprinting and field investigation of in situ biodegradation. AB - RATIONALE: The manufacturing and uses of hexachlorocyclohexane (HCH) have resulted in a serious environmental challenge and legacy. This study highlights the ability of compound specific isotope analysis (CSIA) to distinguish among various HCH sources and to support the evaluation of the potential for in situ biodegradation in contaminated groundwater. METHODS: Tests were conducted to verify the absence of significant isotope fractionation during HCH sample pre concentration including dichloromethane extraction, solvent exchange into iso octane, and H2SO4 clean-up, and analysis by gas chromatography/combustion-isotope ratio mass spectrometry (GC/C-IRMS). The method was then applied to four Technical Grade (TG) HCH mixtures procured from different sources and to groundwater samples from a contaminated site. RESULTS: The pre-concentration method enabled determination of carbon isotope ratios (delta(13)C values) of HCH isomers with no significant isotopic fractionation. The TG-HCH mixtures had significantly different delta(13)C values. Moreover, for any given TG-HCH, all isomers had delta(13)C values within 1.10/00 of each other - a distinctly uniform fingerprint. At the HCH-contaminated field site, compared with source wells, downgradient wells showed significant (up to 5.10/00) enrichment in (13)C and the delta(13)C values of the HCH isomers were significantly different from each other. CONCLUSIONS: A method was successfully developed for the CSIA of HCH isomers that showed potential for HCH source differentiation and identification of HCH in situ biodegradation. At the HCH-contaminated site, the observed preferential isotopic enrichment of certain isomers relative to others for a given source allows differentiation between biodegraded and non-biodegraded HCH. PMID- 26160417 TI - Proton-bound complex mediating retro-Michael-type fragmentation of protonated 3 substituted oxindoles in the Orbitrap high-energy collisional dissociation cell. AB - RATIONALE: Oxindole derivatives are valuable building blocks for indole chemistry. Systematically exploring the fragmentation behavior of the protonated 3-pyrazole-substituted oxindoles by kinetic methods combined with density functional theory (DFT) calculations is useful for further understanding their basic properties, and might provide some insights into their reactivity trends in synthesis and metabolism. METHODS: All high-resolution high-energy collision induced dissociation tandem mass spectrometry (CID-MS/MS) experiments were carried out using electrospray ionization hybrid Quadrupole-Orbitrap mass spectrometry in positive ion mode. Theoretical calculations were carried out by the DFT method at the B3LYP level with the 6-311G (d, p) basis set in the Gaussian 03 package of programs. RESULTS: In the fragmentation of protonated 3 pyrazole-substituted oxindoles, the characterized protonated 3-(3-methyl-5-oxo-1H pyrazol-4(5H)-ylidene)indolin-2-one derivatives and the protonated 5 methylpyrazolone were observed, which were proposed from the cleavage of the C(beta)-C(gamma) bond in a retro-Michael reaction. With the kinetic plot, a linear correlation was established between the intensities of this two competitive product ions and the difference in proton affinities of the corresponding neutral molecules, which demonstrated that the retro-Michael reaction was mediated by a proton-bound complex. CONCLUSIONS: Using the kinetic method combined with theoretical calculations, a proton-bound complex mediating retro-Michael reaction was proposed for the fragmentation of protonated 3 pyrazole-substituted oxindoles in the high-energy collisional dissociation tandem mass spectrometry for the first time, which provided potential evidence to further understand their intrinsic bioactivities. PMID- 26160418 TI - Glutathione trapping of reactive drug metabolites produced by biomimetic metalloporphyrin catalysts. AB - RATIONALE: Metalloporphyrins can be useful in the production of drug metabolites, as they enable easier production of oxidative metabolites usually produced by the cytochrome P450 enzymes. Our aim was to test metalloporphyrin-based biomimetic oxidation (BMO) methods for production and S-glutathione trapping of reactive drug metabolites in addition to phase I metabolites. METHODS: Clozapine, ticlopidine and citalopram were selected as model compounds. These were incubated with the BMO assay and the incubations were analyzed with high-resolution liquid chromatography/mass spectrometry (LC/MS) and tandem mass spectrometry (LC/MS/MS). Additionally, incubations with human liver S9 fraction were performed to compare the results with the BMO assay. RESULTS: Six glutathione conjugates were identified for clozapine from the S9 incubation, while the BMO assay produced four of these. Four out of the five phase I metabolites produced by S9 were detected using the BMO assay. For ticlopidine, four glutathione conjugates were detected from the S9 incubation, but none of these were observed using the BMO assay. Eight of the nine phase I metabolites produced by S9 incubation were detected in the BMO assay. As expected, no glutathione conjugates were detected for citalopram, and the same three phase I metabolites were detected in both S9 and BMO incubations. CONLUSIONS: Differences in formation of GSH-trapped reactive metabolites by BMO assay between clozapine and ticlopidine are probably due to different reactive intermediates and reaction mechanisms. The reactive intermediate of clozapine, the nitrenium ion was generated, but the reactive intermediates of ticlopidine, S-oxide and epoxide, were not detected from the incubations. However, the results show that for selected cases the use of biomimetic assays can be used to produce high amounts of S-glutathione conjugates identical to those from liver subfraction incubations, on a scale that is relevant for purification and subsequent identification by NMR spectroscopy; which is often difficult using incubations with liver subfractions. PMID- 26160419 TI - Molecular architecture of novel potentially bioactive (co)oligoesters containing pesticide moieties established by electrospray ionization multistage mass spectrometry. AB - RATIONALE: Pesticides are commonly used in agriculture to ensure high crop yield; however, because of their low resistance to environmental conditions, a large amount of pesticides does not reach target pests and becomes an environmental pollutant. One of the ways to reduce these drawbacks is synthesis of polymeric systems, which allows for controlled release of pesticides for a prolonged period of time. Herein we report the synthesis and characterization of novel potentially bioactive (co)oligoesters with bioactive moieties (selected from pesticides) which are covalently linked along an oligoester backbone. METHODS: The delivery systems of pesticides were prepared via anionic ring-opening polymerization of beta-substituted beta-lactones containing bioactive moieties as a pendant group selected from pesticides and their copolymerization with beta-butyrolactone in the presence of carboxylates as initiators. Electrospray ionization multistage mass spectrometry (ESI-MS(n)) supported by (1)H NMR were applied in order to establish the structure, at a molecular level, of the new biodegradable oligomeric release system of selected pesticides. RESULTS: Based on ESI-MS(n) analyses, the structures of the resulting (co)oligoesters were established at the molecular level. The ESI-MS/MS allowed to confirm the structures of end groups and to determine the composition of individual (co)oligoester molecules which contained one, two or three bioactive molecules per (co)oligomer. Additionally, it was shown that fragmentation of selected ions of potentially bioactive (co)oligoesters proceeded via random breakage of ester bonds along the oligomer chain and ester bonds of the bioactive pendant group. CONCLUSIONS: An analytical method for detailed structural characterization at the molecular level of potentially bioactive (co)oligoesters has been developed. These results are important in the analysis of designed biodegradable polymeric controlled-release systems of pesticides with potential agricultural applications. PMID- 26160420 TI - Stem cell therapy for kidney disease. AB - INTRODUCTION: Kidney diseases are a global public health problem whose incidence is rapidly growing due to a global rise in the aged population and the increasing prevalence of cardiovascular disease, hypertension and diabetes. With the emergence of stem cells as potential therapeutic agents, attempts in using them to significantly reduce the burden of these diseases have increased. AREAS COVERED: Several types of stem cells have been proven to be likely candidates for treating kidney diseases. We discuss in detail the potential use of mesenchymal stem cells in preclinical and clinical works, with additional populations that have been studied briefly described. Moreover, we discuss current knowledge on endogenous kidney regeneration ability and on the possibility to modulate it using chemical and biological agents. EXPERT OPINION: Stem cell therapy is a promising new treatment for kidney disease documented in many animal studies. Mesenchymal stem cells have emerged as a promising cell type, but their efficacy in clinical trials is still controversial. Identification of progenitor cells in the adult kidney is another step forward in regenerative medicine, suggesting the repair potential of the adult kidney and the possible modulation of renal progenitors in situ using pharmacological approaches. PMID- 26160421 TI - The effect of synthetic pyrethroids on the attachment and host-feeding behaviour in Dermacentor reticulatus females (Ixodida: Amblyommidae). AB - BACKGROUND: The high competence of D. reticulatus in transmission of tick-borne pathogens prompts investigations of the effect of chemicals used as repellents and acaricides on the behaviour of the tick on the host. Therefore, this paper presents the effect of permethrin and deltamethrin on the attachment and feeding in this tick species. FINDINGS: Attachment to rabbit skin of D. reticulatus females sprayed with pyrethroids and the effect of different doses thereof on feeding were assessed at a temperature of 20 +/- 3 degrees C and 50% humidity. The dynamics of attachment of D. reticulatus females varied in a dose-dependent manner after the application of both pyrethroids. Within the first 0.5 h of the experiments, there was an over six-fold and over twelve-fold increase in the number of females attached to host skin after application of permethrin concentrations of 0.3906-0.7812 MUg and 1.5625-3.1250 MUg/1 specimen, respectively. In the case of deltamethrin, females treated with the dose of 0.0390 MUg of the compound were able to attach to host skin only 4 hours after the infestation. The toxic activity of both pyrethroids increased the duration of the feeding period and decreased the body weight of engorged females and the feeding efficiency index. CONCLUSIONS: The accelerated attachment of D. reticulatus females caused by sublethal permethrin doses and delayed or inhibited attachment caused by deltamethrin suggest a necessity of careful selection of the type and dose of pyrethroids to protect hosts from tick attacks. PMID- 26160422 TI - Opening of a respiratory intermediate care unit in a general hospital: impact on mortality and other outcomes. AB - BACKGROUND: Respiratory intermediate care units (RICUs) are specialized areas aimed at optimizing the cost-benefit ratio of care. No data exist about the impact of opening a RICU on hospital outcomes. OBJECTIVES: We wondered if opening a RICU may improve the outcomes of patients with acute respiratory failure (ARF), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or community-acquired pneumonia (CAP). METHODS: We analyzed the discharge abstracts of 2,372 admissions to the RICU and internal medicine units (IMUs) for ARF, AECOPD, and CAP. The IMUs at the Hospital of Trieste comprise emergency and internal wards. In order to investigate the determinants of outcomes, a matched case-control study was performed using clinical records. RESULTS: The in-hospital mortality rate was lower in the RICU vs. IMUs (5.4 vs. 19.1%, p = 0.0001). Statistical differences did not change when comparing the RICU with the emergency and internal wards. After adjusting for potential confounders, the risk of death for patients with CAP, AECOPD, or ARF was significantly higher in the IMUs than in the RICU (OR 6.90, 3.19, and 6.7, respectively, p < 0.04). Both the frequency of transfer to the ICU (6 vs. 12%, p = 0.0001, OR 0.38) and the hospital stay (9.3 vs. 12.1 days, p = 0.0001) were reduced in patients admitted to the RICU compared to those admitted to non-RICUs. Significant differences were found in care management concerning chest physiotherapy, mechanical ventilation, antibiotics, and corticosteroids. CONCLUSIONS: The opening of a RICU may be advantageous to reduce in-hospital mortality, the need for ICU admission, and the hospital stay of patients with AECOPD, CAP, and ARF. Better use of care resources contributed to better patient management in the RICU. PMID- 26160423 TI - Is long-term exposure to traffic pollution associated with mortality? A small area study in London. AB - Long-term exposure to primary traffic pollutants may be harmful for health but few studies have investigated effects on mortality. We examined associations for six primary traffic pollutants with all-cause and cause-specific mortality in 2003-2010 at small-area level using linear and piecewise linear Poisson regression models. In linear models most pollutants showed negative or null association with all-cause, cardiovascular or respiratory mortality. In the piecewise models we observed positive associations in the lowest exposure range (e.g. relative risk (RR) for all-cause mortality 1.07 (95% credible interval (CI) = 1.00-1.15) per 0.15 MUg/m(3) increase in exhaust related primary particulate matter <=2.5 MUm (PM2.5)) whereas associations in the highest exposure range were negative (corresponding RR 0.93, 95% CI: 0.91-0.96). Overall, there was only weak evidence of positive associations with mortality. That we found the strongest positive associations in the lowest exposure group may reflect residual confounding by unmeasured confounders that varies by exposure group. PMID- 26160424 TI - Parkin Is Dispensable for Mitochondrial Function, but Its Ubiquitin Ligase Activity Is Critical for Macroautophagy and Neurotransmitters: Therapeutic Potential beyond Parkinson's Disease. AB - Parkin biology has emerged as an exciting area of pharmaceutical development for several human diseases, including cancer and neurodegeneration. Parkin's role is multifaceted in human health and disease and its function affecting major cellular quality control mechanisms, including the ubiquitin-proteasome and autophagy-lysosome systems, is critical in the maintenance of cellular homeostasis. Loss of Parkin function due to aging, protein instability and gene mutations is manifest in a number of human diseases, contributing to the validation of this protein as a therapeutic target. Parkin activation to mobilize cellular quality control mechanisms and counteract dyshomeostasis is a highly desirable area for therapeutic development. The elucidation of Parkin's crystal structure and better understanding of possible posttranslational modifications (i.e. phosphorylation, ubiquitination, etc.) that regulate Parkin's enzymatic activity suggest that this protein is a therapeutic drug target in many human diseases. Here we review Parkin's role in health and disease and discuss the effects of self-ubiquitination and deubiquitination on Parkin activity. This review provides further evidence showing the longitudinal effects of Parkin deletion on mitochondrial function, oxidative stress and neurotransmitter balance in vivo using high-frequency (1)H/(13)C NMR spectroscopy. PMID- 26160425 TI - Analysis of the Thermal Degradation of the Individual Anthocyanin Compounds of Black Carrot (Daucus carota L.): A New Approach Using High-Resolution Proton Nuclear Magnetic Resonance Spectroscopy. AB - The black carrot dye is a mixture of cyanidin molecules, the nuclear magnetic resonance (NMR) spectrum of which shows a highly overlapped aromatic region. In this study, the (1)H NMR (800 MHz) aromatic chemical shifts of the mixture were fully assigned by overlaying them with the characterized (1)H NMR chemical shifts of the separated compounds. The latter were isolated using reverse-phase high performance liquid chromatography (RP-HPLC), and their chemical shifts were identified using (1)H and two-dimensional (2D) correlation spectroscopy (COSY) NMR spectroscopy. The stability of the black carrot mixture to heat exposure was investigated at pH 3.6, 6.8, and 8.0 by heat-treating aqueous solutions at 100 degrees C and the powdered material at 180 degrees C. From integration of high resolution (1)H NMR spectra, it was possible to follow the relative degradation of each compound, offering advantages over the commonly used ultraviolet/visible (UV/vis) and HPLC approaches. UV/vis spectroscopy and CIE color measurements were used to determine thermally induced color changes, under normal cooking conditions. PMID- 26160426 TI - Declarative strategies persist under increased cognitive load. AB - When humans simultaneously execute multiple tasks, performance on individual tasks suffers. Complementing existing theories, this article poses a novel question to investigate interactions between memory systems supporting multi tasking performance: When a primary and dual task both recruit declarative learning and memory systems, does simultaneous performance of both tasks impair primary task performance because learning in the declarative system is reduced, or because control of the primary task is passed to slower procedural systems? To address this question, participants were trained on either a perceptual categorization task believed to rely on procedural learning or one of three different categorization tasks believed to rely on declarative learning. Task performance was examined with and without a simultaneous dual task thought to recruit working memory and executive attention. To test whether the categories were learned procedurally or declaratively, the response keys were switched after a learning criterion had been reached. Large impairments in performance after switching the response keys are taken to indicate procedural learning, and small impairments are taken to indicate declarative learning. Our results suggest that the declarative memory categorization tasks (regardless of task difficulty) were learned by declarative systems, regardless of whether they were learned under dual-task conditions. PMID- 26160428 TI - Insulin Modulates Liver Function in a Type I Diabetes Rat Model. AB - BACKGROUND/AIMS: Several studies have been performed to unravel the association between diabetes and increased susceptibility to infection. This study aimed to investigate the effect of insulin on the local environment after cecal ligation and puncture (CLP) in rats. METHODS: Diabetic (alloxan, 42 mg/kg i.v., 10 days) and non-diabetic (control) male Wistar rats were subjected to a two-puncture CLP procedure and 6 h later, the following analyses were performed: (a) total and differential cell counts in peritoneal lavage (PeL) and bronchoalveolar lavage (BAL) fluids; (b) quantification of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL- 6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 in the PeL and BAL fluids by enzyme-linked immunosorbent assay (ELISA); (c) total leukocyte count using a veterinary hematology analyzer and differential leukocyte counts on stained slides; (d) biochemical parameters (urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) by colorimetric analyses); and (e) lung, kidney, and liver morphological analyses (hematoxylin and eosin staining). RESULTS: Relative to controls, non-diabetic and diabetic CLP rats exhibited an increased in the concentration of IL-1beta, IL-6, IL-10, CINC 1, and CINC-2 and total and neutrophil in the PeL fluid. Treatment of these animals with neutral protamine Hagedorn insulin (NPH, 1IU and 4IU, respectively, s.c.), 2 hours before CLP procedure, induced an increase on these cells in the PeL fluid but it did not change cytokine levels. The levels of ALT, AST, ALP, and urea were higher in diabetic CLP rats than in non-diabetic CLP rats. ALP levels were higher in diabetic sham rats than in non-diabetic sham rats. Treatment of diabetic rats with insulin completely restored ALT, AST, and ALP levels. CONCLUSION: These results together suggest that insulin attenuates liver dysfunction during early two-puncture CLP-induced peritoneal inflammation in diabetic rats. PMID- 26160427 TI - The differential outcomes procedure can overcome self-bias in perceptual matching. AB - There are biases in perceptual matching between shapes and labels referring to familiar others, compared with when the labels refer to unfamiliar people. We assessed whether these biases could be affected by differential feedback (using the differential outcomes procedure [DOP]) compared with when feedback is provided using a nondifferential outcomes procedure (NOP). Participants formed associations between simple geometric shapes and labels referring to people the participant did or did not know (self, best friend, other). Subsequently, the task was to match a label to one of two shapes shown on a trial. When feedback for correct responses was given following the NOP condition, matches were faster to known people (self and friend) compared with those to an unknown person (stranger). However, this advantage for known personal relations was eliminated when participants were given feedback for correct responses following the DOP condition. The data are consistent with prior work showing that the DOP can facilitate the learning of taxing associations (for the stranger stimuli relative to the familiar self and friend stimuli). In addition, the results suggest that the facilitated perceptual matching for stimuli associated to individuals known personally may reflect better individuation of the association between the shape stimulus and the label, a process enhanced by using a DOP for associations with unfamiliar people. PMID- 26160429 TI - Guadecitabine (SGI-110) priming sensitizes hepatocellular carcinoma cells to oxaliplatin. AB - Promoter DNA hypermethylation is an important biomarker of hepatocellular carcinoma (HCC), supporting the potential utility of demethylating agents in this disease. Guadecitabine (SGI-110) is a second-generation hypomethylating agent formulated as a dinucleotide of decitabine and deoxyguanosine that yields longer half-life and more extended decitabine exposure than decitabine IV infusion. Here we performed preclinical evaluation of SGI-110 in HCC models to guide the design of a phase I/II clinical trial. HCC cell lines and xenograft models were used to determine the antitumor activity of SGI-110 as a single agent and in combination with oxaliplatin. Pretreatment with low doses of SGI-110 significantly synergized with oxaliplatin yielding enhanced cytotoxicity. The combination of SGI-110 and oxaliplatin was well tolerated and significantly delayed tumor growth in mice compared to oxaliplatin alone. Bromouridine-labeled RNA sequencing (Bru-seq) was employed to elucidate the effects of SGI-110 and/or oxaliplatin on genome-wide transcription. SGI-110 and the combination treatment inhibited the expression of genes involved in WNT/EGF/IGF signaling. DNMT1 and survivin were identified as novel PD markers to monitor the efficacy of the combination treatment. In conclusion, SGI-110 priming sensitizes HCC cells to oxaliplatin by inhibiting distinct signaling pathways. We expect that this combination treatment will show low toxicity and high efficacy in patients. Our study supports the use of the combination of low doses of SGI-110 and oxaliplatin in HCC patients. PMID- 26160431 TI - Novel Functions of the Anticoagulant Activated Protein C in Maintaining Skin Barrier Integrity to Impact on Skin Disease. AB - The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. When the barrier is disrupted any of a number of diseases, such as chronic wounds, psoriasis, pemphigus, atopic dermatitis or toxic epidermal necrolysis, can take hold. Activated protein C (APC) or its precursor, protein C, is abundantly expressed by skin epidermal keratinocytes and stimulates their proliferation and migration, and inhibits apoptosis and inflammation, leading to a healing phenotype. Importantly, APC also increases the barrier function of keratinocytes by promoting expression and cell-cell contact redistribution of tight junction proteins. These cytoprotective properties of APC on epidermal keratinocytes place it as an exciting new therapy for skin disorders associated with the disruption of barrier function and inflammation. PMID- 26160430 TI - Hepatocellular carcinoma: Where there is unmet need. AB - Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor most commonly associated with underlying chronic liver disease, especially hepatitis. It is a growing problem in the United States and worldwide. There are two potential ways to prevent HCC. Primary prevention which is based on vaccination or secondary prevention involving agents that slow down carcinogenesis. Several pathways have been thought to play a role in the development of HCC; specifically, those involving vascular endothelial growth factor (VEGF)-mediated angiogenesis, WNT, phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and c-MET. Currently, there are only a limited number of drugs which have been proven as effective treatment options for HCC and several clinical trials are testing drugs which target aberrations in the pathways mentioned above. In this review, we discuss currently approved therapies, monotherapies and combination therapy for the treatment of HCC. PMID- 26160432 TI - Three-Dimensional Innervation Zone Imaging from Multi-Channel Surface EMG Recordings. AB - There is an unmet need to accurately identify the locations of innervation zones (IZs) of spastic muscles, so as to guide botulinum toxin (BTX) injections for the best clinical outcome. A novel 3D IZ imaging (3DIZI) approach was developed by combining the bioelectrical source imaging and surface electromyogram (EMG) decomposition methods to image the 3D distribution of IZs in the target muscles. Surface IZ locations of motor units (MUs), identified from the bipolar map of their MU action potentials (MUAPs) were employed as a prior knowledge in the 3DIZI approach to improve its imaging accuracy. The performance of the 3DIZI approach was first optimized and evaluated via a series of designed computer simulations, and then validated with the intramuscular EMG data, together with simultaneously recorded 128-channel surface EMG data from the biceps of two subjects. Both simulation and experimental validation results demonstrate the high performance of the 3DIZI approach in accurately reconstructing the distributions of IZs and the dynamic propagation of internal muscle activities in the biceps from high-density surface EMG recordings. PMID- 26160433 TI - Influence of endogenous NEFA on beta cell function in humans. AB - AIMS/HYPOTHESIS: It is a commonly held view that chronically elevated NEFA levels adversely affect insulin secretion and insulin action (lipotoxicity). However, the effect of NEFA on beta cell function has only been explored using acute NEFA elevations. Our aim was to analyse the relationship between endogenous NEFA levels and beta cell function. METHODS: In 1,267 individuals followed-up for 3 years, we measured insulin sensitivity (by clamp) and beta cell function (by C peptide modelling during OGTT and as the acute insulin response [AIR] to IVGTT). RESULTS: At baseline, both fasting and insulin-suppressed NEFA levels were higher across glucose tolerance groups, while insulin sensitivity was lower, insulin output was higher, and beta cell glucose sensitivity and AIR were lower (all p < 0.0001). In multiple logistic analyses adjusting for age, BMI, WHR and glucose tolerance, both fasting and insulin-suppressed NEFA levels were inversely related to insulin sensitivity, as expected (both p < 0.0001). Furthermore, after adjusting for insulin sensitivity, insulin-suppressed NEFA were positively associated with total insulin output (p = 0.0042). In contrast, neither fasting nor insulin-suppressed NEFA were related to beta cell glucose sensitivity or AIR. At follow-up, worsening of glucose tolerance (n = 126) was predicted by lower insulin and beta cell glucose sensitivity. In this model, baseline NEFA were not significant predictors of progression. CONCLUSIONS/INTERPRETATION: In the non diabetic state and in subjects with impaired glucose tolerance, circulating endogenous NEFA are not independently associated measures of beta cell function, and do not predict deterioration of glucose tolerance. Thus, in the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort there is no evidence for beta cell lipotoxicity of endogenous total NEFA concentrations. PMID- 26160435 TI - Erratum to: Prevalence of Helicobacter pylori Infection Worldwide: A Systematic Review of Studies with National Coverage. PMID- 26160434 TI - CDK5 knockdown in astrocytes provide neuroprotection as a trophic source via Rac1. AB - Astrocytes perform metabolic and structural support functions in the brain and contribute to the integrity of the blood-brain barrier. Astrocytes influence neuronal survival and prevent gliotoxicity by capturing glutamate (Glu), reactive oxygen species, and nutrients. During these processes, astrocytic morphological changes are supported by actin cytoskeleton remodeling and require the involvement of Rho GTPases, such as Rac1. The protein cyclin-dependent kinase 5 (CDK5) may have a dual effect on astrocytes because it has been shown to be involved in migration, senescence, and the dysfunction of glutamate recapture; however, its role in astrocytes remains unclear. Treating a possible deregulation of CDK5 with RNAi is a strategy that has been proposed as a therapy for neurodegenerative diseases. Models of glutamate gliotoxicity in the C6 astroglioma cell line, primary cultures of astrocytes, and co-cultures with neurons were used to analyze the effects of CDK5 RNAi in astrocytes and the role of Rac1 in neuronal viability. In C6 cells and primary astrocytes, CDK5 RNAi prevented the cell death generated by glutamate-induced gliotoxicity, and this finding was corroborated by pharmacological inhibition with roscovitine. This effect was associated with the appearance of lamellipodia, protrusions, increased cell area, stellation, Rac1 activation, BDNF release, and astrocytic protection in neurons that were exposed to glutamate excitotoxicity. Interestingly, Rac1 inhibition in astrocytes blocked BDNF upregulation and the astrocyte-mediated neuroprotection. Actin cytoskeleton remodeling and stellation may be a functional phenotype for BDNF release that promotes neuroprotection. In summary, our findings suggest that CDK5- knockdown in astrocytes acts as a trophic source for neuronal protection in a Rac1-dependent manner. PMID- 26160436 TI - Erratum to: Worldwide Burden of Gastric Cancer Attributable to Tobacco Smoking in 2012 and Predictions for 2020. PMID- 26160437 TI - Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease. AB - BACKGROUND: The gastrointestinal (GI) microbiome is recognized for potential clinical relevance in inflammatory bowel disease (IBD). Data suggest that there is a disease-dependent loss of microbial diversity in IBD. Trimethylamine-N-oxide (TMAO) is generated by GI anaerobes through the digestion of dietary phosphatidylcholine and carnitine in a microbial-mammalian co-metabolic pathway. IBD-related changes in the gut microbiome may result in disease-specific changes in TMAO plasma concentrations. AIM: To determine whether TMAO plasma levels in IBD are altered compared to controls and whether they correlate with disease presence or activity. METHODS: Liquid chromatography-tandem mass spectrometry was used to measure TMAO, choline, and carnitine plasma levels in 479 subjects (373 non-IBD controls, 106 IBD). Subjects were also genotyped for the flavin monooxygenase (FMO)3 variants, E158K and E308G. RESULTS: Plasma TMAO levels were 2.27 uM lower in the IBD population compared to the control population (p = 0.0001). Lower TMAO levels were similarly seen in active ulcerative colitis (UC) (1.56 uM) versus inactive disease (3.40 uM) (p = 0.002). No difference was seen in active Crohn's disease (CD) versus inactive CD. No intergroup variation existed in plasma TMAO levels based on FMO3 genotype. Choline levels were higher in IBD, while carnitine levels were similar between the two groups, suggesting that lower TMAO levels in IBD were not due to dietary differences. CONCLUSIONS: Decreased TMAO levels are seen in IBD compared to a non-IBD population. These data suggest that TMAO may have potential as a biomarker to support IBD diagnosis as well as to assess disease activity in UC. PMID- 26160438 TI - MicroRNA-103a-3p controls proliferation and osteogenic differentiation of human adipose tissue-derived stromal cells. AB - The elucidation of the molecular mechanisms underlying the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs) represents a critical step in the development of hADSCs-based cellular therapies. To examine the role of the microRNA-103a-3p (miR-103a-3p) in hADSCs functions, miR-103a-3p mimics were transfected into hADSCs in order to overexpress miR-103a-3p. Osteogenic differentiation was induced for 14 days in an osetogenic differentiation medium and assessed by using an Alizarin Red S stain. The regulation of the expression of CDK6 (cyclin-dependent kinase 6), a predicted target of miR-103a-3p, was determined by western blot, real-time PCR and luciferase reporter assays. Overexpression of miR-103a-3p inhibited the proliferation and osteogenic differentiation of hADSCs. In addition, it downregulated protein and mRNA levels of predicted target of miR-103a-3p (CDK6 and DICER1). In contrast, inhibition of miR-103a-3p with 2'O methyl antisense RNA increased the proliferation and osteogenic differentiation of hADSCs. The luciferase reporter activity of the construct containing the miR-103a-3p target site within the CDK6 and DICER1 3'-untranslated regions was lower in miR-103a-3p transfected hADSCs than in control miRNA-transfected hADSCs. RNA interference mediated downregulation of CDK6 and DICER1 in hADSCs inhibited their proliferation and osteogenic differentiation. The results of the current study indicate that miR-103a-3p regulates the osteogenic differentiation of hADSCs and proliferation of hADSCs by direct targeting of CDK6 and DICER1 partly. These findings further elucidate the molecular mechanisms governing the differentiation and proliferation of hADSCs. PMID- 26160439 TI - The potential role of the sodium iodide symporter gene polymorphism in the development of differentiated thyroid cancer. AB - The sodium iodide symporter (NIS) (solute carrier family 5; SLC5A), mediates the active transport of iodine anion (I(-)) into thyroid follicular cells to facilitate thyroid hormone biosynthesis. Considering its fundamental role in thyroid function, our objective in this study is to explore its potential involvement in the pathogenesis of differentiated thyroid cancer (DTC). Following a preliminary sequencing of the gene in a representative sample of the general population, five variants, (1) rs45602038, (2) rs4808708, (3) rs4808709, (4) rs7250346 and (5) rs12327843, were selected for a larger population-based association study consisting of 507 cases and 597 controls, of which only the rs45602038_TT [Odds ratio (95% confidence interval)=1.90 (1.26-2.88); p=0.002] was associated with disease following adjustment for other confounders using the multivariate analysis. Furthermore, a 5-mer haplotype CGAGT constructed from the five studied SNPs conferred a significant risk (chi(2)=10.98; p=0.0009) for DTC. This association trickled down through shorter derivatives, with the 4-mer haplotype CGAG (chi(2)=13.25; p=0.0003) displaying the most significant association and the 3-mer GAG (chi(2)=11.80; p=0.0006) being equally strongly linked to the disease. Comparison of the flanking derivatives of the primary 5 mer haplotype also indicated that the 3-mer CGA (chi(2)=4.04; p=0.045) constructed from SNP block 1-3 was a lot weaker than that of the AGT (chi(2)=6.73; p=0.0095) constructed from the blocks 3-5 from the other end of the gene. Put together, these data implicate the three nucleotide changes at the rs4808708, rs4808709 and rs7250346 loci (blocks 2-4) as the core for this relationship. PMID- 26160440 TI - Role of microRNA-101a in the regulation of goat skeletal muscle satellite cell proliferation and differentiation. AB - MicroRNAs are a class of small, non-coding RNAs that participate in the regulation of diverse biological processes including skeletal muscle development. However, the underlying molecular mechanisms are not fully understood, particularly in goat. Here, we identified goat miR-101a as a novel myogenic microRNA mediating myogenic differentiation. The expression of miR-101a was enriched in goat skeletal muscles and up-regulated during satellite cell differentiation. After transfection with a miR-101a mimic and culturing in differentiation medium, satellite cell differentiation was promoted, accompanied by a significant increase in mRNA expression of the myogenic marker, MyoG, and decreased expression of MyoD. In contrast, blocking the function of miR-101a with a 2'-O-methylated antisense oligonucleotide inhibitor repressed satellite cell differentiation. However, both gain- and loss-of-function studies demonstrated that miR-101a had no significant influence on satellite cell proliferation. Therefore, our results provide a new insight on miR-101a in the regulation of goat skeletal muscle satellite cell proliferation and differentiation. PMID- 26160442 TI - Blockade of KCa3.1 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction. AB - BACKGROUND/AIMS: After myocardial infarction (MI), cardiac fibrosis greatly contributes to left ventricular remodeling and heart failure. The intermediate conductance calcium-activated potassium Channel (KCa3.1) has been recently proposed as an attractive target of fibrosis. The present study aimed to detect the effects of KCa3.1 blockade on ventricular remodeling following MI and its potential mechanisms. METHODS: Myocardial expression of KCa3.1 was initially measured in a mouse MI model by Western blot and real time-polymerase chain reaction. Then after treatment with TRAM-34, a highly selective KCa3.1 blocker, heart function and fibrosis were evaluated by echocardiography, histology and immunohistochemistry. Furthermore, the role of KCa3.1 in neonatal mouse cardiac fibroblasts (CFs) stimulated by angiotensin II (Ang II) was tested. RESULTS: Myocardium expressed high level of KCa3.1 after MI. Pharmacological blockade of KCa3.1 channel improved heart function and reduced ventricular dilation and fibrosis. Besides, a lower prevalence of myofibroblasts was found in TRAM-34 treatment group. In vitro studies KCa3.1 was up regulated in CFs induced by Ang II and suppressed by its blocker.KCa3.1 pharmacological blockade attenuated CFs proliferation, differentiation and profibrogenic genes expression and may regulating through AKT and ERK1/2 pathways. CONCLUSION: Blockade of KCa3.1 is able to attenuate ventricular remodeling after MI through inhibiting the pro fibrotic effects of CFs. PMID- 26160441 TI - Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis. AB - OBJECTIVE: To investigate serum antibody reactivity against a panel of post translationally modified vimentin peptides (PTMPs) in patients with early inflammatory arthritis. METHODS: A panel of PTMPs was developed. Microtitre plates were coated with peptides derived from vimentin that were identical in length and composition except at one amino acid that was changed to introduce one of three post-translational modifications (PTMs)-either a citrullinated, carbamylated or acetylated residue. Sera of 268 treatment-naive patients with early inflammatory arthritis and symptoms <=3 months' duration were tested. Patients were assigned to one of three outcome categories at 18-month follow-up (rheumatoid arthritis (RA), persistent non-RA arthritis and resolving arthritis). RESULTS: Antibodies against citrullinated, carbamylated and acetylated vimentin peptides were detected in the sera of patients with early inflammatory arthritis. The proportion of patients seropositive for all antibody types was significantly higher in the RA group than in the other groups. Anti cyclic citrullinated peptide (CCP)-positive patients with RA had higher numbers of peptides recognised and higher levels of antibodies against those peptides, representing a distinct profile compared with the other groups. CONCLUSIONS: We show for the first time that antibodies against acetylated vimentin are present in the sera of patients with early RA and confirm and extend previous observations regarding anticitrullinated and anticarbamylated antibodies. PMID- 26160443 TI - Authors' Reply. PMID- 26160444 TI - Biclustering on expression data: A review. AB - Biclustering has become a popular technique for the study of gene expression data, especially for discovering functionally related gene sets under different subsets of experimental conditions. Most of biclustering approaches use a measure or cost function that determines the quality of biclusters. In such cases, the development of both a suitable heuristics and a good measure for guiding the search are essential for discovering interesting biclusters in an expression matrix. Nevertheless, not all existing biclustering approaches base their search on evaluation measures for biclusters. There exists a diverse set of biclustering tools that follow different strategies and algorithmic concepts which guide the search towards meaningful results. In this paper we present a extensive survey of biclustering approaches, classifying them into two categories according to whether or not use evaluation metrics within the search method: biclustering algorithms based on evaluation measures and non metric-based biclustering algorithms. In both cases, they have been classified according to the type of meta-heuristics which they are based on. PMID- 26160446 TI - Preconcentration of synthetic phenolic antioxidants by using magnetic zeolites derived with carboxylatocalix[4]arenes combined with high performance liquid chromatography. AB - Here, we synthesized a novel organic-inorganic hybrid material combining carboxylatocalix[4]arenes and magnetic zeolites by covalent bonding. The complex was characterized by scanning electron microscopy, transmission electron microscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction spectrometry, thermogravimetric analysis/differential thermal gravity analysis, and by using an X-ray photoelectron spectrometer and a vibrating sample magnetometer. The resulting magnetic composite was employed as a solid phase adsorbent to separate and preconcentrate synthetic phenolic antioxidants. Various interactions between the targets and the adsorbent contributed to the adsorption efficiency including hydrophobic interaction, hydrogen-bond interaction, and pi pi complexation. The superparamagnetic participation in the process of synthesizing zeolites made the separation process of adsorbent from solutions convenient by an external magnetic field. Taking advantage of this property, this adsorbent could be recycled more than 30 times. The concentrations of the preconcentrated SPAs were determined directly by high-performance liquid chromatography. Various experimental parameters were optimized, according to which the method was evaluated. Finally, the prepared magnetic zeolite@carboxylatocalix[4]arene was successfully applied to identify synthetic phenolic antioxidants from juice and infant milk powder samples with high enrichment factors in the range of 41.9-92.5. The magnetic materials allowed rapid and simple preconcentration, implying their potential in the field of adsorption. PMID- 26160445 TI - Effect of otitis media with effusion on cochlear implant surgery: technical difficulties, post-operative complications and outcome. AB - OBJECTIVE: This study evaluated the complications and outcomes of cochlear implantation in patients who had otitis media with effusion at the time of surgery. METHODS: A retrospective chart review study was performed of 87 consecutive paediatric patients (age range 22 months to 10 years, mean 4.8 years) who underwent successful cochlear implantation, with follow-up periods of 5-6 years. All patients had unilateral implants, with eight on the left side. All devices were activated two weeks after implantation. The effect of the middle-ear condition on the procedure, post-operative complications and outcome were evaluated. RESULTS: Unilateral ears of 17 otitis media with effusion patients were implanted with some surgical difficulties but no long-term post-operative complications. CONCLUSION: For children admitted for cochlear implantation who are subsequently found to have otitis media with effusion, surgeons should be aware of possible surgical difficulties. Greater intra-operative risks should be anticipated and more surgical time allowed for cochlear implantation in these patients. PMID- 26160447 TI - Police and clinician diversion of people in mental health crisis from the Emergency Department: a trend analysis and cross comparison study. AB - BACKGROUND: The Northern Police and Clinician Emergency Response (NPACER), a combined police and clinician second response team, was created to divert people in mental health crisis away from the hospital emergency department (ED) to care in the community or direct admission to acute inpatient services. The aim of this study was to evaluate the NPACER by comparing trends in service utilisation prior to and following its inception. METHODS: A retrospective comparison of electronic records was undertaken with interrupted time series analysis to assess the impact of NPACER on ED presentations over 27-months (N = 1776). Chi-squared tests were used to analyze service utilization; (1) in the six-months before and after the implementation of NPACER and (2) within the post NPACER period between times of the day it was operational. RESULTS: NPACER reduced the number of mental health crisis presentations to the ED. When the NPACER team was operational, 16% of people in crisis went to ED compared with 100% for all other times of the day, over a six-month period. The NPACER team enabled direct access to the inpatient unit for 51 people assessed at a police station and in the community compared with no direct access when NPACER was not operational. CONCLUSIONS: NPACER enabled reductions in presentations to the ED by diverting people to more appropriate and less restrictive environments. The model also facilitated direct admission to acute inpatient mental health services when people in crisis were assessed in the community or transported to a police station for assessment. PMID- 26160448 TI - Prevalence of Hepatitis C Virus and Hepatitis B Virus Infections in Patients Infected with HIV Through Blood Donation or Transfusion in China. PMID- 26160449 TI - Search for a natural killer: a case report. PMID- 26160450 TI - Association between alcohol consumption and multiple sclerosis: a meta-analysis of observational studies. AB - To investigate the association between alcohol consumption and multiple sclerosis risk, we performed a systematic literature search of PubMed, EmBase and Web of Science databases for all relevant articles regarding alcohol and multiple sclerosis. Our meta-analysis consisted of 10 studies, including nine case controls and one cohort study. The odds ratios (OR) of the association between alcohol consumption and multiple sclerosis were 0.92 [95 % confidence interval (CI) 0.73-1.17] overall, 0.91 (95 % CI 0.39-2.41) for prospective study, and 0.92 (95 % CI 0.72-1.19) for retrospective studies. In addition, neither subgroup analyses nor sensitivity analyses showed a substantially change in the pooled OR and 95 % CI. Meta-analysis showed that there is no evidence that alcohol consumption is associated with an increased risk of multiple sclerosis. There may be a potential protective effect of alcohol consumption on MS incidence, however, this trend may not be obvious and should be validated by further research. PMID- 26160451 TI - Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration. AB - Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (KATP) channels have been identified in ASMCs. Mount evidence has suggested that KATP channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K(+) channels triggers K(+) efflux, which leading to membrane hyperpolarization, preventing Ca(2+)entry through closing voltage-operated Ca(2+) channels. Intracellular Ca(2+) is the most important regulator of muscle contraction, cell proliferation and migration. K(+) efflux decreases Ca(2+) influx, which consequently influences ASMCs proliferation and migration. As a KATP channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2'-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca(2+)/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective KATP channel antagonist. These findings provide a strong evidence to support that Ipt antagonize the proliferating and migrating effects of PDGF-BB on human ASMCs through opening KATP channels. Altogether, our results highlighted a novel profile of Ipt as a potent option against the airway remodeling in chronic airway diseases. PMID- 26160452 TI - Imaging membrane remodeling during regulated exocytosis in live mice. AB - In this mini-review we focus on the use of time-lapse light microscopy to study membrane remodeling during protein secretion in live animals. In particular, we highlight how subcellular intravital microscopy has enabled imaging the dynamics of both individual secretory vesicles and the plasma membrane, during different steps in the exocytic process. This powerful approach has provided us with the unique opportunity to unravel the role of the actin cytoskeleton in regulating this process under physiological conditions, and to overcome the shortcomings of more reductionist model systems. PMID- 26160453 TI - The action of HIF-3alpha variants on HIF-2alpha-HIF-1beta heterodimer formation is directly probed in live cells. AB - Hypoxia-inducible factors (HIFs), consisting of alpha and beta subunits, activate various genes to adapt to low oxygen environments through their heterodimeric complex formation in the nucleus. While most of the studies have been extensively focused on the HIF-1alpha isoform, the effect of HIF-alpha isoforms on the complex formation between HIF-2alpha and HIF-1beta in live cells has not been reported in detail. To probe these interactions in a physiological condition, we established a fluorescence resonance energy transfer (FRET) assay by introducing fluorescent reporter proteins onto the N-termini of HIF-2alpha and HIF-1beta in live PC3 cells. After thorough validations of our FRET assay system, we showed that both HIF-1alpha and HIF-3alpha variants likely function as negative regulators on the heterodimer formation of HIF-2alpha with HIF-1beta in cells. We also characterized the localization and stabilization of HIF-3alpha variants and measured the interaction between HIF-3alpha variants and other HIF isoforms in live cells. In contrast to the previous results showing HIF-3alpha-mediated blockage of HIF-1alpha translocation, the presence of HIF-3alpha did not affect the localization of HIF-2alpha, suggesting distinct roles of HIF-3alpha in regulation of two HIF-alpha isoforms. PMID- 26160454 TI - In Vitro Differentiation of Embryonic Stem Cells into Hematopoietic Lineage: Towards Erythroid Progenitor's Production. AB - Embryonic stem cells (ESCs) differentiation via embryoid body (EB) formation is an established method that generates the three germ layers. However, EB differentiation poses several problems including formation of heterogeneous cell populations. Herein, we described a differentiation protocol on enhancing mesoderm derivation from murine ESCs (mESCs) using conditioned medium (CM) from HepG2 cells. We used this technique to direct hematopoiesis by generating "embryoid-like" colonies (ELCs) from murine (m) ESCs without following standard formation of EBs. Our CM-mESCs group yielded an almost fivefold increase in ELC formation (p <= 0.05) and higher expression of mesoderm genes;-Brachyury-T, Goosecoid, and Flk-1 compared with control mESCs group. Hematopoietic colony formation from CM-mESCs was also enhanced by twofold at days 7 and 14 with earlier colony commitment compared to control mESCs (p <= 0.05). This early clonogenic capacity was confirmed morphologically by the presence of nucleated erythrocytes and macrophages as early as day 7 in culture using standard 14-day colony-forming assay. Early expression of hematopoietic primitive (zeta-globin) and definitive (beta-globin) erythroid genes and proteins was also observed by day 7 in the CM-treated culture. These data indicate that hematopoietic cells more quickly differentiate from CM-treated, compared with those using standard EB approaches, and provide an efficient bioprocess platform for erythroid-specific differentiation of ESCs. PMID- 26160455 TI - Unique binding behaviour of water-soluble polycationic oxacalix[4]arene tweezers towards the paraquat dication. AB - The first water-soluble polycationic oxacalix[4]arene molecular tweezers able to recognize - under pH control - the paraquat dication as a result of a delicate balance between electrostatic repulsion, Coulombic shielding and attractive pi stacking interactions are reported. PMID- 26160457 TI - Cross validation of the prognostic and diagnostic utility of tobacco craving in a general and a pregnant sample of treatment-seeking smokers. AB - BACKGROUND: Valid and reliable brief measures of tobacco craving are necessary for research and clinical purposes. However, comparisons of the utility of single item and brief multidimensional craving measures are scarce. METHODS: We analyzed two tobacco craving measures, the French versions of the 12-item Tobacco Craving Questionnaire (FTCQ-12) and the single craving item on the Minnesota Nicotine Withdrawal Scale, in pregnant and non-pregnant (females and males) French smokers from two independent smoking cessation trials. Using data from pregnant smokers, we estimated first a prognostic model for each measure and compared their ability to predict relapse from one visit to the next. We next used cutoff values for both measures to determine how well craving distinguished current smokers from abstainers. For cross-validation, we tested how well the same cut-off values generalized to non-pregnant smokers. RESULTS: Two FTCQ-12 factors (Expectancy and Purposefulness) predicted smoking status; scores were higher in pregnant non abstainers than abstainers. The sum of these two factors, FTCQ-12 risk score (RS), yielded higher sensitivity both in prognostic and diagnostic models than single-item MNWS craving. FTCQ-12 RS had higher sensitivity among pregnant than non-pregnant smokers. Specificity of both tobacco craving measures was similar among pregnant smokers, but higher with MNWS craving than with FTCQ-12 RS in non pregnant smokers. CONCLUSIONS: FTCQ-12 RS and MNWS craving can be used together in clinical practice to rapidly predict smoking status. Interventions targeting Expectancy and Purposefulness may result in higher likelihood of abstinence, especially among pregnant smokers. PMID- 26160456 TI - Cardiac LXRalpha protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization. AB - Pathological cardiac hypertrophy is characterized by a shift in metabolic substrate utilization from fatty acids to glucose, but the molecular events underlying the metabolic remodeling remain poorly understood. Here, we investigated the role of liver X receptors (LXRs), which are key regulators of glucose and lipid metabolism, in cardiac hypertrophic pathogenesis. Using a transgenic approach in mice, we show that overexpression of LXRalpha acts to protect the heart against hypertrophy, fibrosis, and dysfunction. Gene expression profiling studies revealed that genes regulating metabolic pathways were differentially expressed in hearts with elevated LXRalpha. Functionally, LXRalpha overexpression in isolated cardiomyocytes and murine hearts markedly enhanced the capacity for myocardial glucose uptake following hypertrophic stress. Conversely, this adaptive response was diminished in LXRalpha-deficient mice. Transcriptional changes induced by LXRalpha overexpression promoted energy-independent utilization of glucose via the hexosamine biosynthesis pathway, resulting in O GlcNAc modification of GATA4 and Mef2c and the induction of cytoprotective natriuretic peptide expression. Our results identify LXRalpha as a key cardiac transcriptional regulator that helps orchestrate an adaptive metabolic response to chronic cardiac stress, and suggest that modulating LXRalpha may provide a unique opportunity for intervening in myocyte metabolism. PMID- 26160458 TI - Sniping and other high-risk smoking practices among homeless youth. AB - BACKGROUND: This study of homeless youth uses quantitative data to estimate the prevalence of high-risk smoking practices (obtaining or using cigarettes in a way that increase exposure to toxins and/or susceptibility to infectious diseases) and identify characteristics associated in particular with sniping (smoking discarded cigarettes), and qualitative data to describe why and how homeless youth engage in sniping. METHODS: A probability sample of 292 homeless youth smokers in Los Angeles County completed a self-administered survey, and a separate convenience sample of 27 homeless youth who were lifetime smokers participated in focus groups. Survey participants reported on background characteristics, smoking cognitions, and high-risk smoking practices. Focus group participants described how they obtained cigarettes and responses relevant to sniping were coded. RESULTS: Survey results indicated that nearly all youth engaged in at least one high-risk smoking practice, with three-quarters having sniped cigarettes in the past 30 days. Sniping was more frequent among youth with less negative smoking attitudes (b=-0.29, 95% CI=-0.55 to -0.04, p=0.02), greater nicotine dependence (b=0.11, 95% CI=0.00 to 0.23, p=0.046), lower income (b= 0.05, 95% CI=-0.09 to -0.01, p=0.02), and more severe drug abuse (b=0.15, 95% CI=0.04, 0.26, p=0.01). Focus groups data indicated that youth snipe because it provides cheap and easy access to tobacco, and use specific strategies to mitigate the perceived health risks of sniping. CONCLUSIONS: Sniping and other high-risk smoking practices deserve further attention among homeless youth, particularly those already facing greater health threats due to factors such as nicotine dependence, lower income, and drug abuse. PMID- 26160459 TI - CGMD: An integrated database of cancer genes and markers. AB - Integrating cancer genes and markers with experimental evidence might provide valuable information for the further investigation of crosstalk between tumor genes and markers in cancer biology. To achieve this objective, we developed a database known as the Cancer Gene Marker Database (CGMD), which integrates data on tumor genes and markers based on experimental evidence. The major goal of CGMD is to provide the following: 1) current systematic treatment approaches and recent advances in different cancer treatments; 2) the aggregation of different genes and markers by their molecular characteristics and pathway associations; and 3) free access to the data compiled by CGMD at http://cgmd.in/. The database consists of 309 genes and 206 markers, as well as a list of 40 different human cancers, with detailed descriptions of all characterized markers. CGMD provides complete cancer annotations and molecular descriptions of cancer genes and markers such as CpG islands, promoters, exons, PDB structures, active sites and domains. PMID- 26160460 TI - Perceived Social Norms for Intimate Partner Violence in Proximal and Distal Groups. AB - This study investigated students' perceived descriptive social norms for intimate partner violence (IPV) among proximal and distal groups at college. Male and female college students estimated the prevalence rates for IPV among same-sex friends (proximal group) and same-sex "typical students" (distal group). In separate regression equations for men and women, perceived estimates of IPV rates for same-sex friends, but not estimates for same-sex typical students, were positively related with the participants' own IPV behaviors. Findings have important implications for IPV prevention and intervention programs for college students. PMID- 26160461 TI - Acute symptomatic calcific discitis in adults: a case report and review of literature. AB - Symptomatic calcific discitis has been reported in the paediatric population but is a rare entity in adults with only eight cases reported in the English literature. We present a case of adult calcific discitis presenting with acute onset back pain. Radiographs and CT demonstrated central T11-T12 disc calcification with diffuse marrow oedema on subsequent MRI. The patient was referred to our spinal oncology unit due to the extensive marrow oedema as a possible underlying primary bone tumour. Review of the CT confirmed an end-plate defect with herniated calcific nucleus pulposus with no underlying bone lesion. Features were in keeping with acute calcific discitis. The patient was treated symptomatically and made an uneventful recovery. We discuss the characteristic imaging features seen on radiograph, CT and MRI and review the current literature. Calcific discitis is a self-limiting pathology requiring symptomatic management only. Radiologists need to be aware of this rare entity as it can occur in adults and may be mistaken for a more sinister pathology such as infective discitis or a bone tumour and lead to further unnecessary imaging or invasive procedures. PMID- 26160462 TI - A case of silent perforated diverticulitis in the ascending colon combined with pylephlebitis resulting in complete occlusion of the portal trunk. AB - A case of silent perforated diverticulitis in the ascending colon combined with pylephlebitis, resulting in complete occlusion of the portal trunk, is presented. A 75-year-old man with no relevant medical history visited our hospital complaining of a fever, which had lasted for 2 weeks. Although his laboratory data were indicative of severe inflammation, an abdominal examination and a computed tomography (CT) scan did not produce any significant findings. On the 6th day after admission, an abdominal CT scan detected a thrombus extending from the superior mesenteric vein to the portal vein, but did not show any signs of infection. However, on the 40th day after admission, an abdominal CT scan detected an embolus in the portal vein completely occluding the main portal trunk, as well as marked edematous changes indicative of inflammation, and an abscess in the ascending colon. We performed laparotomy and iliocecal resection, during which a perforation of the ascending colon derived from diverticulitis was found. We report this rare case and a review of the literature. PMID- 26160463 TI - The assessment of anorexia in patients with cancer: cut-off values for the FAACT A/CS and the VAS for appetite. AB - PURPOSE: Anorexia is a frequently observed symptom in patients with cancer and is associated with limited food intake and decreased quality of life. Diagnostic instruments such as the Anorexia/Cachexia Subscale (A/CS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire and the visual analog scale (VAS) for appetite have been recommended in the assessment of anorexia, but validated cut-off values are lacking. This study aimed to obtain cut-off values of these instruments for the assessment of anorexia in patients with cancer. METHODS: The FAACT-A/CS and the VAS for appetite were administered to patients with cancer before start of chemotherapy. As reference standard for anorexia, two external criteria were used: (1) a cut-off value of >=2 on the anorexia symptom scale of the EORTC QLQ C-30 and (2) the question "Do you experience a decreased appetite?" (yes/no). ROC curves were used to examine the optimal cut-off values for the FAACT-A/CS and VAS. RESULTS: A total of 273 patients (58 % male; 64.0 +/- 10.6 years) were included. The median score on the FAACT-A/CS was 38 (IQR 32-42) points and 77 (IQR 47-93) points on the VAS. Considering both external criteria, the optimal cut-off value for the FAACT-A/CS was <=37 (sensitivity (se) 80 %, specificity (sp) 81 %, positive predictive value (PV(+)) 79 %, negative predictive value (PV(-)) 82 %) and for the VAS was <=70 (se 76 %, sp 83 %, PV(+) 80 %, PV(-) 79 %). CONCLUSIONS: For the assessment of anorexia in patients with cancer, our study suggests cut-off values of <=37 for the FAACT-A/CS and <=70 for the VAS. Future studies should confirm our findings in other patient samples. PMID- 26160464 TI - Constipation in specialized palliative care: factors related to constipation when applying different definitions. AB - CONTEXT: For patients in palliative care, constipation is primarily a result of opioid treatment. Impacts from other factors related to constipation in palliative care are rarely studied. OBJECTIVES: The aim was to identify factors related to constipation in patients in palliative care, and then to compare these factors between patients with different types of constipation and patients without constipation. METHODS: Cross-sectional data on constipation was collected with a 26-item questionnaire from 485 patients in 38 specialist palliative care units in Sweden. Three different constipation groups were used; MC ONLY, PC ONLY, and MC & PC. Logistic regression analyses were used to calculate odds ratios. RESULTS: Patients with <3 defecations/week, MC ONLY, (n = 36) had higher odds of being hospitalized, bed-restricted, in need of personal assistance for toilet visits, and of having a poor fluid intake. Patients with the perception of being constipated, PC ONLY, (n = 93) had higher odds of having poor appetite, hemorrhoids, hard stool, more opioid treatment, less laxative treatment and of being more dissatisfied with constipation information. Patients with both <3 defecations/week and a perception of being constipated, MC & PC, (n = 78) had higher odds of having cancer- disease. CONCLUSION: There were several significant factors related to constipation with higher odds than opioid- treatment, for patients in palliative care, such as; hard stool, cancer diagnosis, dissatisfaction with information, low fluid intake, hemorrhoids, bed restriction, hospitalization, and need of personal assistance for toilet visits. PMID- 26160465 TI - Controlling the on/off current ratio of ferroelectric field-effect transistors. AB - The on/off current ratio in organic ferroelectric field-effect transistors (FeFETs) is largely determined by the position of the threshold voltage, the value of which can show large device-to-device variations. Here we show that by employing a dual-gate layout for the FeFET, we can gain full control over the on/off ratio. In the resulting dual-gate FeFET the ferroelectric gate provides the memory functionality and the second, non-ferroelectric, control gate is advantageously used to set the threshold voltage. The on/off ratio can thus be maximized at the readout bias. The operation is explained by the quantitative analysis of charge transport in a dual-gate FeFET. PMID- 26160466 TI - Adverse Outcomes After Initial Non-surgical Management of Subdural Hematoma: A Population-Based Study. AB - BACKGROUND: Little is known about the natural history of non-surgically managed subdural hematoma (SDH). The purpose of this study is to determine rates of adverse events after non-surgical management of SDH and whether these outcomes differ depending on traumatic versus nontraumatic etiology. A retrospective cohort study was conducted using administrative claims data on all emergency department visits and acute care hospitalizations at nonfederal facilities in California from 2005 to 2011, Florida from 2005 to 2012, and New York from 2006 to 2011. We included patients who were discharged home after hospitalization with a first-recorded diagnosis of SDH and no record of surgical hematoma evacuation. METHODS: Patients were followed for readmission with SDH, readmission for surgical SDH evacuation, and fatal readmission with SDH. Survival statistics and the log-rank test were used to compare rates of these adverse events after traumatic versus nontraumatic SDH. Multivariable Cox regression analysis was used to compare hazards for traumatic versus nontraumatic etiology while adjusting for age, sex, race, insurance status, presence of dementia, alcohol use, acquired abnormalities in coagulation, acquired abnormalities in platelet function, hypertension, atrial fibrillation, venous thromboembolism, ischemic stroke, coronary heart disease, and valvular disease. RESULTS: We identified 27,502 conservatively treated patients with SDH, of which 70.9% were traumatic and 29.1% nontraumatic. Compared to patients with traumatic SDH, patients with nontraumatic SDH had significantly higher rates of subsequent hospitalization with SDH (cumulative 90-day rates: 15.3 % [95% CI 14.5-16.1%] vs. 10.3% [95% CI 9.9 10.8%]), surgical SDH evacuation (7.8% [95% CI 7.3-8.5%] vs. 5.5% [95% CI 5.2 5.8%]), and SDH-related in-hospital death (1.0% [95% CI 0.8-1.2%] vs. 0.4% [95 % CI 0.3-0.5%]). In multivariable Cox regression analysis, nontraumatic etiology was associated with a higher hazard of readmission with SDH (HR 1.4; 95% CI 1.3 1.5), surgery (HR 1.3; 95% CI 1.2-1.4), and in-hospital mortality (HR 1.9; 95% CI 1.4-2.5). Our findings were unchanged in sensitivity analyses that also adjusted for Elixhauser comorbidities. CONCLUSIONS: Approximately one in eight patients with a conservatively managed SDH was readmitted with SDH within 90 days. A substantial proportion of these readmissions involved surgical hematoma evacuation. These outcomes occurred significantly more often after nontraumatic as compared to traumatic SDH. PMID- 26160467 TI - Modelling consumer intakes of vegetable oils and fats. AB - Vegetable oils and fats make up a significant part of the energy intake in typical European diets. However, their use as ingredients in a diverse range of different foods means that their consumption is often hidden, especially when oils and fats are used for cooking. As a result, there are no reliable estimates of the consumption of different vegetable oils and fats in the diet of European consumers for use in, for example, nutritional assessments or chemical risk assessments. We have developed an innovative model to estimate the consumption of vegetable oils and fats by European Union consumers using the European Union consumption databases and elements of probabilistic modelling. A key feature of the approach is the assessment of uncertainty in the modelling assumptions that can be used to build user confidence and to guide future development. PMID- 26160468 TI - Acute and Midterm Outcome After MitraClip Therapy in Patients With Severe Mitral Regurgitation and Left Ventricular Dysfunction. AB - The clinical outcome of patients with severe primary and secondary mitral regurgitation (MR) and heart failure or significantly reduced left ventricular ejection fraction (LVEF) who underwent percutaneous mitral valve repair (pMVR) is yet not well known. This study compares midterm outcome of patients with severe left ventricular dysfunction (EF <=30%) versus patients with slightly or moderately reduced or normal LVEF (EF >30%) after pMVR. One hundred thirty-six consecutive patients were enrolled: 42 patients displayed severe left ventricular dysfunction, group 1 (logistic EuroSCORE I 27.7 +/- 21.8%; secondary MR in 37 patients), and 94 patients displayed slightly or moderately reduced or normal LVEF, group 2 (logistic EuroSCORE I 17 +/- 18.2%; secondary MR in 21 patients). The primary efficacy endpoint was death of any cause, repeat mitral valve intervention, and/or New York Heart Association class >=III, which was reached in 31% of patients in group 1 versus 40% in group 2 (p = 0.719) at a median follow up of 371 days. MR, graded by transthoracic echocardiography, was reduced in both groups (p <0.001) and New York Heart Association class improved in each group (p <0.001), with no differences between groups (p >0.05). In conclusion, at midterm follow-up, the pMVR provided significant clinical benefits with comparable results achieved both in patients with significantly reduced and in patients with moderately reduced to normal LVEF. Thus, pMVR represents a feasible and effective treatment in high-risk patients who otherwise have limited therapeutic options and no safe option to reduce MR. PMID- 26160469 TI - Quercetin in brain diseases: Potential and limits. AB - Quercetin is a ubiquitous flavonoid present in beverages, food and plants that has been demonstrated to have a role in the prevention of neurodegenerative and cerebrovascular diseases. In neuronal culture, quercetin increases survival against oxidative insults. Antioxidation appears to be a necessary but not sufficient condition for its neuroprotective action and modulation of intracellular signaling and transcription factors, increasing the expression of antioxidant and pro survival proteins and modulating inflammation, appears as important for neuronal protection. Quercetin also regulates the activity of kinases, changing the phosphorylation state of target molecules, resulting in modulation of cellular function and gene expression. Concentrations of quercetin higher than 100 MUM consistently show cytotoxic and apoptotic effects by its autoxidation and generation of toxic quinones. In vivo, results are controversial with some studies showing neuroprotection by quercetin and others not, requiring a drug delivery system or chronic treatments to show neuroprotective effects. The blood and brain bioavailability of free quercetin after ingestion is a complex and controversial process that produces final low concentrations, a fact that has led to suggestions that metabolites would be active by themselves and/or as pro drugs that would release the active aglycone in the brain. Available studies show that in normal or low oxidative conditions, chronic treatments with quercetin contributes to re-establish the redox regulation of proteins, transcription factors and survival signaling cascades that promote survival. In the presence of highly oxidative conditions such as in an ischemic tissue, quercetin could become pro-oxidant and toxic. At present, evidence points to quercetin as a preventive molecule for neuropathology when administered in natural matrices such as vegetables and food. More research is needed to support its use as a lead compound in its free form in acute treatments, requiring new pharmaceutical formulations and/or structural changes to limit its pro-oxidant and toxic effects. PMID- 26160470 TI - Social stress as a cause of diseases in farm animals: Current knowledge and future directions. AB - Over the past 50 years, biomedical research has established a strong linkage between psychosocial stress and disease risk in humans, which has transformed the understanding of stress and the role it plays in human lives. This research has led to personalized medicine where a reduction in daily life stress is a main goal for many people with debilitating illnesses. This review describes the supporting evidence that social stress also plays a critical role in farm animal disease prevention, and may be a mediator by which common management practices can increase disease risk. There is evidence that social factors, including deprivation of social contact ('social isolation'), reducing space allowance ('crowding') and disturbing social order ('social instability') trigger physiological and behavioral indicators of stress in livestock. Less research exists, however, linking management practices that trigger social stress with higher disease risk. Suggestions are offered for future research opportunities, and practical, evidence-based recommendations are made for reducing the negative effects of social isolation, instability and crowding. The current evidence that social factors contribute to disease risk in farm animals is not as convincing as the human literature, but remains a promising and important area for future research. PMID- 26160471 TI - Preparation and characterization of an immunoaffinity column for the selective extraction of aflatoxin B1 in 13 kinds of foodstuffs. AB - A rapid and reliable immunoaffinity column (IAC) clean-up based ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of aflatoxin B1 (AFB1) in cereals, peanuts, vegetable oils and Chinese traditional food products like sufu and lobster sauce. The immunoaffinity column of AFB1 (AFB1-IAC) was prepared by coupling CNBr-activated Sepharose-4B with the anti-AFB1 monoclonal antibody. The column capacity of IAC was over 260ng/mL gel. Samples were extracted with methanol-water (60:40, v/v) and the extracts were then purified on an AFB1-IAC before UPLC-MS/MS analysis. The average recoveries of AFB1 in spiked samples at levels of 1.0, 5.0 and 10.0MUg/kg ranged from 72% to 98%, with the relative standard deviations of 1.2 9.3% (n=6). The limits of qualification ranged from 0.07 to 0.23MUg/kg, which were below the MRLs of AFB1 in the matrices evaluated. In this work, the developed method was suitable for the determination of trace AFB1 residues in 13 kinds of foodstuffs. PMID- 26160472 TI - Quantification of miltefosine in peripheral blood mononuclear cells by high performance liquid chromatography-tandem mass spectrometry. AB - Phagocytes, the physiological compartment in which Leishmania parasites reside, are the main site of action of the drug miltefosine, but the intracellular pharmacokinetics of miltefosine remain unexplored. We developed a bioanalytical method to quantify miltefosine in human peripheral blood mononuclear cells (PBMCs), expanding from an existing high performance liquid chromatography-tandem mass spectrometry method for the quantification of miltefosine in plasma. The method introduced deuterated miltefosine as an internal standard. Miltefosine was extracted from PBMC pellets by addition of 62.5% methanol. Supernatant was collected, evaporated and reconstituted in plasma. Chromatographic separation was performed on a reversed phase C18 column and detection with a triple-quadrupole mass spectrometer. Miltefosine was quantified using plasma calibration standards ranging from 4 to 1000ng/mL. This method was validated with respect to its PBMC matrix effect, selectivity, recovery and stability. No matrix effect could be observed from the PBMC content (ranging from 0.17 to 26.3*10(6)PBMCs) reconstituted in plasma, as quality control samples were within 3.0% of the nominal concentration (precision less than 7.7%). At the lower limit of quantitation of 4 ng/mL plasma, corresponding to 0.12ng/10(6) PBMCs in a typical clinical sample, measured concentrations were within 8.6% of the nominal value. Recovery showed to be reproducible as adding additional pre-treatment steps did not increase the recovery with more than 9%. This method was successfully applied to measure intracellular miltefosine concentrations in PBMC samples from six cutaneous leishmaniasis patients up to one month post-treatment. PMID- 26160474 TI - Novel therapeutic targets for steatohepatitis. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western hemisphere and is growing as an indication for liver transplantation. There are currently no approved therapies for NAFLD, especially its aggressive phenotype non-alcoholic steatohepatitis (NASH). However, there has been an explosion of information related to NASH that provides detailed data on the molecular pathogenesis of NASH and its progression to cirrhosis. The current review summarizes the pathophysiological rationale for the selection of specific targets for the treatment of NASH and provides an overview of the current strategies being used for the treatment of NASH and the pathophysiological rationale for the use of these strategies. Specifically, those targets that are being studied in both alcoholic and non-alcoholic steatohepatitis are also mentioned. PMID- 26160473 TI - Suppressed diversity of survivin splicing in active rheumatoid arthritis. AB - INTRODUCTION: Alternative splicing distinguishes normal and pathologic cells. High levels of oncoprotein survivin recognise patients with severe rheumatoid arthritis (RA). Here, we assess clinical relevance of alternative splicing of survivin in leukocytes of peripheral blood (PBMC) and bone marrow (BM) in RA patients. METHOD: Transcription of survivin wild-type (survivin-WT), survivin-2B and survivin-DeltaEx3 was measured in 67 randomly selected RA patients and in 23 patients before and after B cell depletion with rituximab. Analysis was done in relation to disease activity, anti-rheumatic treatment and serum levels of rheumatoid factor (RF) and survivin. RESULTS: Survivin-WT was the dominant splice variant equally expressed in T and B cells, while survivin-2B and survivin DeltaEx3 were higher in B cells. High disease activity (DAS28>5.1) was associated with an excess of survivin-WT and low ratios between survivin-2B/WT (p=0.035) and survivin-DeltaEx3/WT in PBMC. Depletion of B cells by rituximab caused a decrease in survivin-WT (p=0.005) in PBMC, increasing the ratio between survivin-2B/WT (p=0.009) and survivin-DeltaEx3/WT (p=0.001) in BM. This increase in survivin 2B/WT was associated with reduction in CD19+ BM cells (r=0.929, p=0.007), RF (IgM, r=0.857, p=0.024; IgA, r=0.739, p=0.021), and DAS28 (0.636, p=0.054). The increase in survivin-DeltaEx3 in BM was associated with a reduction of CD19+ BM cells (r=0.714, p=0.058) and DAS28 (r=0.648, p=0.049), while survivin-DeltaEx3/WT was associated with RF (IgG, r=0.882, p=0.016). CONCLUSION: This study demonstrates that the suppressed diversity of survivin splicing in leukocytes may attribute to adverse self-recognition in RA. Depletion of autoantibody producing B cells improves the balance of survivin splicing. PMID- 26160475 TI - Genetic polymorphisms and oxidative stress in non-alcoholic steatohepatitis (NASH): A mini review. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease, thus becoming an epidemic in the Western world with a major impact on public health. NAFLD encompasses a large spectrum of disease ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and may progress to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The role of genetic polymorphisms is not clear. Evidence supports the hypothesis that genetic factors are involved in the predisposition to NAFLD, and thus should emphasize the polygenic nature of the disease as a limiting factor in these studies. However, the polymorphic allele associated with increased hepatic steatosis appears to be associated with various different combinations of phenotypes, including increase or decrease of the biochemical and clinical parameters. It is possible that SNPs in genes involved in excessive fatty acid oxidation would predispose to NASH. On the other hand, the SNPs could determine the inadequate mitochondrial overload during times of excessive FFA supply. However due to the multiple hits involving some pathways, a brief review of genetic variants on mediators of oxidative stress, inflammation and lipid metabolism pathways is presented. It is clear that the discovery of genetic and environmental associations, robust enough to direct the treatment and to trace specific prevention strategies would only be possible with studies examining the susceptibility of NAFLD in a number of individuals considerably higher than assessed so far. These studies need a large number of well phenotyped cases and controls and certainly require national and international collaboration. PMID- 26160476 TI - Making the most of new genetic risk factors - genetic and epigenetic fine mapping of causal autoimmune disease variants. PMID- 26160477 TI - Serum IgG4 and IgG for the diagnosis of autoimmune pancreatitis: A systematic review with meta-analysis. AB - BACKGROUND AND OBJECTIVE: The correct diagnosis of autoimmune pancreatitis (AIP) is a clinical challenge. Emerging published data on the accuracy of serum IgG4 and IgG for diagnosing AIP are inconsistent. This study was performed to better elucidate the accuracy of serum IgG4 and IgG in diagnosing AIP. METHODS: A comprehensive literature search of PubMed, Web of Science, EMBASE, the Cochrane Library and some other databases was conducted before October 2014. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Random-effects model was used to summarize the sensitivity, specificity and other measures of accuracy. RESULTS: Fifteen studies on IgG4 and 8 studies on IgG were included. The summary estimates for serum IgG4 in distinguishing AIP from the overall controls, pancreatic cancer and ordinary chronic pancreatitis were as follows: sensitivity 0.74 (0.70-0.77), 0.73 (0.69-0.77) and 0.76 (0.72-0.80), respectively, specificity, 0.94 (0.93-0.95), 0.93 (0.91-0.95) and 0.96 (0.95 0.97), respectively. The summary estimates for serum IgG in distinguishing AIP from the overall controls and pancreatic cancer were as follows: sensitivity, 0.53 (0.47-0.59) and 0.51 (0.44-0.57), respectively, specificity, 0.87 (0.85 0.89) and 0.94 (0.91-0.96), respectively. The area under the curve (AUC) of serum IgG in distinguishing AIP from ordinary chronic pancreatitis was 0.657. CONCLUSIONS: Both serum IgG4 and IgG have high specificity and relatively low sensitivity for diagnosing AIP. Besides, they are useful for distinguishing AIP from pancreatic cancer and ordinary chronic pancreatitis. To better elucidate the usefulness of serum IgG4 and IgG, further studies are needed. PMID- 26160479 TI - Capsule Commentary on Leykum et al., the Association Between Sensemaking During Physician Team Rounds and Hospitalized Patients' Outcomes. PMID- 26160478 TI - The effect of urinary and arterial blood pH on the progression of acute kidney injury in critically ill patients with systemic inflammatory response syndrome or sepsis and oliguria. AB - PURPOSE: The aim of this study was to examine the relationship between urinary and arterial blood pH and the progression of acute kidney injury in critically ill patients with sepsis or SIRS and oliguria. DESIGN AND SETTING: A prospective observational study was performed on critically ill adults in a tertiary intensive care unit in Melbourne, Australia. Urinary and arterial blood pH were measured at 12 hourly intervals for 60h for patients with sepsis or SIRS, oliguria and who were at high risk of acute kidney injury. Patient RIFLE class at baseline and 60h were assessed for an association to urinary and arterial blood pH. Secondarily, change in peak serum creatinine from baseline over 5 days was assessed for an association to mean urinary and arterial blood pH in the first 48h of the study. Finally, relevant patient demographic and physiological variables were assessed for an association to change in peak serum creatinine from baseline over 5 days. RESULTS: 44 patients were included in the study; 13 did not survive to hospital discharge. Baseline arterial blood pH was associated with baseline RIFLE class but not RIFLE class at 60h. Urinary pH was not associated with RIFLE class at baseline or 60h. There was no association between mean urinary or arterial blood pH in the first 48h and change in peak serum creatinine from baseline over 5 days. None of the patient and demographic and physiological variables showed an association to change in peak serum creatinine from baseline in the 5-day study period. CONCLUSION: Urinary and arterial blood pH were not associated with the progression of acute kidney injury in critically ill patients with sepsis or SIRS and at risk of acute kidney injury. PMID- 26160481 TI - Capsule Commentary on Trowbridge et al., Development and Impact of a Novel Academic Primary Compensation Model. PMID- 26160480 TI - Patient and Stakeholder Engagement in the PCORI Pilot Projects: Description and Lessons Learned. AB - BACKGROUND: Patients and healthcare stakeholders are increasingly becoming engaged in the planning and conduct of biomedical research. However, limited research characterizes this process or its impact. OBJECTIVE: We aimed to characterize patient and stakeholder engagement in the 50 Pilot Projects funded by the Patient-Centered Outcomes Research Institute (PCORI), and identify early contributions and lessons learned. DESIGN: A self-report instrument was completed by researchers between 6 and 12 months following project initiation. PARTICIPANTS: Forty-seven principal investigators or their designees (94 % response rate) participated in the study. MAIN MEASURES Self-report of types of stakeholders engaged, stages and levels of engagement, facilitators and barriers to engagement, lessons learned, and contributions from engagement were measured. KEY RESULTS: Most (83 %) reported engaging more than one stakeholder in their project. Among those, the most commonly reported groups were patients (90 %), clinicians (87 %), health system representatives (44 %), caregivers (41 %), and advocacy organizations (41 %). Stakeholders were commonly involved in topic solicitation, question development, study design, and data collection. Many projects engaged stakeholders in data analysis, results interpretation, and dissemination. Commonly reported contributions included changes to project methods, outcomes or goals; improvement of measurement tools; and interpretation of qualitative data. Investigators often identified communication and shared leadership strategies as "critically important" facilitators (53 and 44 % respectively); lack of stakeholder time was the most commonly reported challenge (46 %). Most challenges were only partially resolved. Early lessons learned included the importance of continuous and genuine partnerships, strategic selection of stakeholders, and accommodation of stakeholders' practical needs. CONCLUSIONS: PCORI Pilot Projects investigators report engaging a variety of stakeholders across many stages of research, with specific changes to their research attributed to engagement. This study identifies early lessons and barriers that should be addressed to facilitate engagement. While this research suggests potential impact of stakeholder engagement, systematic characterization and evaluation of engagement at multiple stages of research is needed to build the evidence base. PMID- 26160482 TI - Capsule Commentary on Dolan et al., The Effectiveness of a Physician-Only and Physician-Patient Intervention on Colorectal Cancer Screening Discussions Between Providers and African American and Latino Patients. PMID- 26160483 TI - Cervical Cancer Screening for Patients on the Female-to-Male Spectrum: a Narrative Review and Guide for Clinicians. AB - Guidelines for cervical cancer screening have evolved rapidly over the last several years, with a trend toward longer intervals between screenings and an increasing number of screening options, such as Pap/HPV co-testing and HPV testing as a primary screening. However, gynecological recommendations often do not include clinical considerations specific to patients on the female-to-male (FTM) spectrum. Both patients and providers may not accurately assess risk for HPV and other sexually transmitted infections, understand barriers to care, or be aware of recommendations for cervical cancer screening and other appropriate sexual and reproductive health services for this patient population. We review the evidence and provide guidance on minimizing emotional discomfort before, during, and after a pelvic exam, minimizing physical discomfort during the exam, and making adaptations to account for testosterone-induced anatomical changes common among FTM patients. PMID- 26160484 TI - Adiponectin and Endometrial Cancer: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: This study evaluates the association between serum adiponectin concentrations and the risk of endometrial cancer through a comprehensive meta analysis of currently available clinical data. METHODS: PubMed, Embase, the Chinese Biomedical Literature Database and the Science Citation Index (ISI Web of Science) were searched for studies that examined the association between blood adiponectin concentrations and the risk of endometrial cancer. Data from studies that met the inclusion criteria were systematically reviewed, and pooled analyses were performed according to the guidelines of Meta-Analysis of Observational Studies in Epidemiology and PRIMSA. RESULTS: Eight case-control studies (including 1257 endometrial cancer patients and 2008 controls) and four nested case-control studies (including 659 endometrial cancer patients and 1398 controls) were included. We found that serum adiponectin level was inversely correlated with the risk of endometrial cancer development after pooling the case control studies (OR = 0.50, 95% CI: 0.39-0.60; P < 0.001). However, meta-analysis of nested case-control studies thus far did not support a broad linkage between serum adiponectin level and endometrial cancer, although a correlation may exist in the subgroup of postmenopausal women (OR=0.81, 95%CI: 0.65-1.00; P=0.060), particularly in postmenopausal women without current hormone replacement therapy (OR = 0.62, 95% CI: 0.44-0.86; P = 0.004). CONCLUSIONS: Meta-analysis of currently available clinical evidence supports the association between high serum adiponectin concentration and reduced risk of endometrial cancer development, particularly in the group of postmenopausal women without current hormone replacement therapy. However, additional studies with prospective design are required to fully support this linkage. PMID- 26160485 TI - Induction of Haemeoxygenase-1 Directly Improves Endothelial Function in Isolated Aortas from Obese Rats through the Ampk-Pi3k/Akt-Enos Pathway. AB - BACKGROUND: Induction of haemeoxygenase-1 (HO-1) increases adiponectin secretion by remodeling adipose tissue in obesity. The objective of our study is to explore whether HO-1 induction directly improves endothelial function independent of adiponectin changes in obese rats. METHODS: Rats were divided into control and obesity groups. Aortic endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Vascular segments of the obese rats were incubated in an organ bath in the presence or absence of cobalt protoporphyrin (CoPP) or CoPP plus stannous protoporphyrin. Nitric oxide (NO) production, superoxide anion production and NF-kappaB p65 expression in the aorta were determined. The expression of AMP-activated kinase (AMPK), Akt and endothelial nitric oxide synthase (eNOS) in endothelial cells was determined by western blotting. The aortic rings from the obese rats were then incubated with CoPP in the presence of specific inhibitors of AMPK, phosphatidylinositol 3 kinase (PI3K) or eNOS. RESULTS: Acetylcholine-induced EDV was significantly attenuated in the obese rats, compared with the NC group (p < 0.05). Pre incubation of vessels from obese rats with CoPP significantly increased EDV (p < 0.05). However, this beneficial effect of CoPP was partly attenuated in vitro in the presence of inhibitors of AMPK, PI3K or eNOS. HO-1 induction with CoPP significantly increased the activation of the AMPK-PI3K/Akt-eNOS pathway and NO production in parallel with reduced superoxide anion production and NF-kappaB p65 expression in obese rats. CONCLUSIONS: HO-1 induction with CoPP directly improved endothelial function in obese rats independent of adiponectin changes. The mechanism of this protective effect is related to increasing NO production by activation of the AMPK-PI3K/Akt-eNOS signaling pathway. PMID- 26160486 TI - Market watch: Therapeutic area 'heat map' for emerging markets. PMID- 26160487 TI - Antivirals for herpes simplex viruses. PMID- 26160488 TI - Iron Status and Inflammation in Early Stages of Chronic Kidney Disease. AB - BACKGROUND/AIMS: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. METHODS: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. RESULTS: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. CONCLUSION: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency. PMID- 26160489 TI - Bilateral aneurysmatic coronary artery-pulmonary artery trunk fistulae. PMID- 26160491 TI - Advances in development of a contraceptive vaccine against human chorionic gonadotropin. AB - INTRODUCTION: There is continuing need for contraceptives. According to World Health Organization, 210 million pregnancies occur each year, out of which some 80 million are unintended. A vaccine offering privacy and periodic intake would be an attractive proposition. AREAS COVERED: The article is a brief review of three vaccines developed against human chorionic gonadotropin (hCG) with progressively better attributes. Clinical trials have proven in more than one country the complete safety and reversibility of the anti-hCG vaccine(s) in women. Vaccination does not entail any disturbance in levels of reproductive tract hormones of the woman or any disturbance in menstrual regularity and bleeding profiles. Phase II clinical trials show the effective prevention of pregnancy in sexually active women of proven fertility. A recombinant vaccine amenable to industrial production has been developed; it induces substantially higher antibody titers in mice of four different genetic strains than those required to prevent pregnancy in women. Rigorous toxicology studies have been completed on this vaccine in rodents and marmosets. EXPERT OPINION: This unique vaccine, requiring periodic intake and demonstrating no impairment of ovulation, hormonal profiles and menstrual regularity, is on the verge of final clinical trials under the aegis of the Indian Council of Medical Research and should be a valuable addition to the available contraceptives. PMID- 26160492 TI - Subcutaneous abatacept in rheumatoid arthritis: current update. AB - INTRODUCTION: A number of biologic agents have been approved for the treatment of rheumatoid arthritis (RA). They have changed the landscape of therapy and demonstrate substantial efficacy with a good safety record. One of these agents is intravenous (i.v.) abatacept (ABA), which has a novel mechanism of action by selectively inhibiting the interaction between T- and antigen-presenting cells. Recently, ABA administered by subcutaneous (s.c.) injection has also been approved for use in RA. In this review, will focus in recent data published in this agent. AREAS COVERED: This paper reviews Phase III clinical trials (ACQUIRE, ACCOMPANY, ALLOW, ATTUNE, AMPLE and AVERT) in terms of clinical efficacy including long-term efficacy, radiographic progression, safety and immunogenicity. EXPERT OPINION: Given the current trend in biologic therapy to s.c. administration, the availability of both i.v. and s.c. ABA provides considerable advantage both to patients and physicians in this competitive environment. The clinical trials have shown comparable efficacy and safety of s.c. ABA to i.v. ABA and others biologics. PMID- 26160493 TI - Development of effective therapy for sporadic ALS. PMID- 26160494 TI - Synthesis and characterization of an antibacterial and non-toxic dimeric peptide derived from the C-terminal region of Bothropstoxin-I. AB - Infectious diseases are among the leading global causes of death, increasing the search for novel antibacterial agents. Among these, biologically active peptides are an excellent research tool. Using solid-phase peptide synthesis (SPPS), this work aimed to synthesize the peptide derived from the C-terminal region of Bothropstoxin-I (BthTX-I) (p-BthTX-I, sequence: KKYRYHLKPFCKK), and its disulfide linked dimeric form, obtained via air oxidation (p-BthTX-I)2. Two other peptides were synthesized to evaluate the dimerization effect on antimicrobial activity. In both sequences, the cysteine (Cys) residue was replaced by the serine (Ser) residue, differing, however, in their C-terminus position. The antimicrobial activity of the peptides against gram-negative (Escherichia (E.) coli) and gram positive (Staphylococcus (S.) aureus) bacteria and yeast (Candida (C.) albicans) was evaluated. Interestingly, only peptides containing the Cys residue showed antimicrobial activity, suggesting the importance of Cys residue and its dimerization for the observed activity. Apparently, p-BthTX-I and (p-BthTX-I)2 did not promote lysis or form pores and were not able to interact with membranes. Furthermore, they neither showed antifungal activity against C. albicans nor toxicity against erythrocytes, epithelial cells, or macrophages, indicating a potential specificity against prokaryotic cells. PMID- 26160495 TI - Unveiling the complexities of Daboia russelii venom, a medically important snake of India, by tandem mass spectrometry. AB - Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of "Big Four" snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management. PMID- 26160496 TI - Imaging of reactive oxygen species in focal ischemic mouse brain using a radical trapping tracer [(3)H]hydromethidine. AB - BACKGROUND: Reactive oxygen species (ROS) have been implicated in the pathophysiology of the brain after ischemic stroke. In this study, we investigate the generation of brain ROS after transient focal ischemia in mice using a radical trapping radiotracer, [(3)H]-labeled N-methyl-2,3-diamino-6-phenyl dihydrophenanthridine ([(3)H]hydromethidine), which we recently reported as a ROS imaging probe. We also examined the effect of dimethylthiourea (DMTU), a hydroxyl radical scavenger, on brain ROS generation and infarct volume after transient focal ischemia in mice. METHODS: [(3)H]Hydromethidine was intravenously injected into mice at 1, 2, 5, and 7 h after transient middle cerebral artery occlusion (tMCAO), and then, the brain autoradiogram was acquired at 60 min after tracer injection. Brain infarct volumes at 24 h after tMCAO were assessed by 2,3,5 triphenyltetrazolium chloride staining. RESULTS: Accumulation of radioactivity was observed in the ipsilateral striatum and cortex at 1 h after tMCAO. The increase of radioactivity was attenuated at 2 h after tMCAO and then became maximized at 5 h. The high accumulation of radioactivity remained until 7 h after tMCAO. DMTU treatment significantly attenuated the accumulation of radioactivity in the ipsilateral hemisphere at 1, 5, and 7 h after tMCAO. Brain infarct volumes were also significantly reduced in DMTU-treated mice at 24 h after tMCAO. CONCLUSIONS: These results indicated that [(3)H]hydromethidine is a useful radiotracer for detecting in vivo brain ROS generation such as hydroxyl radical after ischemic injury. PMID- 26160497 TI - Imaging of reactive oxygen species using [(3)H]hydromethidine in mice with cisplatin-induced nephrotoxicity. AB - BACKGROUND: Reactive oxygen species (ROS) have been implicated in cisplatin induced nephrotoxicity. The aim of this study was to investigate the potential of using [(3)H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([(3)H]hydromethidine) for ex vivo imaging of regional ROS overproduction in mouse kidney induced by cisplatin. METHODS: Male C57BL/6 J mice were intraperitoneally administered with a single dose of cisplatin (30 mg/kg). Renal function was assessed by measuring serum creatinine and blood urea nitrogen (BUN) levels and morphology by histological examination. Renal malondialdehyde levels were measured as a lipid peroxidation marker. Autoradiographic studies were performed with kidney sections from mice at 60 min after [(3)H]hydromethidine injection. RESULTS: Radioactivity accumulation after [(3)H]hydromethidine injection was observed in the renal corticomedullary area of cisplatin-treated mice and was attenuated by pretreatment with dimethylthiourea (DMTU), a hydroxyl radical scavenger. Cisplatin administration significantly elevated serum creatinine and BUN levels, caused renal tissue damage, and promoted renal lipid peroxidation. These changes were significantly suppressed by DMTU pretreatment. CONCLUSIONS: The present study showed that [(3)H]hydromethidine was rapidly distributed to the kidney after its injection and trapped there in the presence of ROS such as hydroxyl radicals, suggesting that [(3)H]hydromethidine is useful for assessment of the renal ROS amount in cisplatin-induced nephrotoxicity. PMID- 26160498 TI - Thermal Vapor Ablation for Lung Lesions in a Porcine Model. AB - BACKGROUND: Various methods for ablating peripheral lung lesions are being investigated; however, none have been successfully adapted for delivery via bronchoscopy. Vapor ablation is currently being used to bronchoscopically create lung volume reduction in emphysema patients. OBJECTIVES: In this study, an adaptation of that technology is evaluated for potential treatment of lung lesions in a live pig model. METHODS: In 5 anesthetized healthy pigs, vapor of varying energy levels was delivered bronchoscopically to 66 different lung subsegments with airway diameters of 2-5 mm. Two hours after treatment, a necropsy was performed and the ablated regions were assessed for ablation and tissue structure disruption. In 6 additional pigs, vapor was applied to 3 subsegments each. To evaluate the progression of the response to treatment, 2 were kept alive for 10 days, 2 for 21 days, and 2 for 32 days. RESULTS: Histopathological evaluation of the sections demonstrated that vapor is capable of creating a uniform field of necrosis following the subsegment anatomical boundary. The reliability of a uniform field is dependent on the level of energy delivered. An energy level that reliably creates a uniform field of necrosis was applied in chronic animals. The animals tolerated the procedure and posttreatment care. No cardiac arrhythmias, hemorrhage, stroke, respiratory distress, or pneumothorax occurred during or after treatment. CONCLUSIONS: Vapor ablation is a potentially safe and efficient means of ablating a targeted region of the lung. We hypothesize that vapor may be useful in treating lesions of the lung in humans. PMID- 26160499 TI - Cardiovascular disease in patients with coeliac disease: A systematic review and meta-analysis. AB - BACKGROUND: Coeliac disease has been associated with an increased risk of cardiovascular disease in some studies, whereas other studies have shown no association. We performed a systematic review and meta-analysis of cardiovascular disease in celiac disease. METHODS: Pubmed, Cinahl, EMBASE and Medline via Ovid were searched for relevant articles published until January 5, 2015. English language articles on studies with more than 20 patients were included, and were quality rated using the GRADE risk of bias tool. We used random-effects models and assessed heterogeneity using the I(2) statistic. RESULTS: Ten studies were relevant, reporting the risk of myocardial infarction, cardiovascular death and stroke in 33,128/32,903/32,466 coeliac disease patients respectively. Only one study examined celiac disease and a composite measure of cardiovascular disease and this study found a hazard ratio of 1.10 (95%CI 1.03-1.28). In a meta analysis, we observed an increased risk of stroke (OR 1.11; 95%CI 1.02-1.20). The risks of myocardial infarction (OR 1.12; 95%CI 0.83-1.40) and cardiovascular death (OR 1.12; 95%CI 0.96-1.29) were similar but were estimated with less certainty. Heterogeneity was low for all outcomes except for myocardial infarction where it was moderate. CONCLUSION: Coeliac disease was associated with a modestly increased risk of cardiovascular disease, but the evidence base is limited. PMID- 26160501 TI - Affective cognition: Exploring lay theories of emotion. AB - Humans skillfully reason about others' emotions, a phenomenon we term affective cognition. Despite its importance, few formal, quantitative theories have described the mechanisms supporting this phenomenon. We propose that affective cognition involves applying domain-general reasoning processes to domain-specific content knowledge. Observers' knowledge about emotions is represented in rich and coherent lay theories, which comprise consistent relationships between situations, emotions, and behaviors. Observers utilize this knowledge in deciphering social agents' behavior and signals (e.g., facial expressions), in a manner similar to rational inference in other domains. We construct a computational model of a lay theory of emotion, drawing on tools from Bayesian statistics, and test this model across four experiments in which observers drew inferences about others' emotions in a simple gambling paradigm. This work makes two main contributions. First, the model accurately captures observers' flexible but consistent reasoning about the ways that events and others' emotional responses to those events relate to each other. Second, our work models the problem of emotional cue integration-reasoning about others' emotion from multiple emotional cues-as rational inference via Bayes' rule, and we show that this model tightly tracks human observers' empirical judgments. Our results reveal a deep structural relationship between affective cognition and other forms of inference, and suggest wide-ranging applications to basic psychological theory and psychiatry. PMID- 26160500 TI - Clinical value of chip-based digital-PCR platform for the detection of circulating DNA in metastatic colorectal cancer. AB - BACKGROUND: The detection of circulating DNA is considered a promising strategy in cancer patients. Digital PCR has emerged as a sensitive method able to quantify both circulating free and tumour DNA. AIM: The aim of this study was to prospectively evaluate the clinical value of a chip-based digital PCR for the detection of circulating DNA. METHODS: Digital PCR was used in 34 metastatic colorectal cancer patients to detect and quantify circulating free and tumour DNA based on K-ras mutational status. Clinical outcomes were analyzed according to circulating DNA measurements. RESULTS: Digital PCR yielded a detection rate of 69% for circulating tumour DNA. The median concentrations of circulating free and tumour DNA were 20 and 6.8 ng/mL, respectively, with significant correlation between both biomarkers (p<0.001). Median overall survival was 4.8 months in patients with high circulating free DNA (>75% quartile) versus not reached in patients with a low level (<25% quartile) (p=0.029). Moreover, median overall survival was significantly decreased in patients with detectable circulating tumour DNA compared to those without (respectively 11.8 months versus not reached, p=0.04). CONCLUSIONS: Chip-based digital PCR is a simple and non invasive method allowing the efficient detection of circulating DNA. Our results highlight that levels of these circulating markers may have a potential prognostic value. PMID- 26160502 TI - Clinical, Histological and Trichoscopic Correlations in Scalp Disorders. AB - Trichoscopy is the term coined for the dermoscopic imaging of scalp and hair. This diagnostic technique, simple and noninvasive, can be used as a handy bedside tool for the diagnosis and follow-up of hair and scalp disorders. It allows the recognition of morphologic structures not visible by the naked eye and provides the clinician with a range of dermoscopic findings necessary for differential diagnosis. Trichoscopy observation can be broadly grouped as interfollicular patterns and follicular patterns. Recently, a third mixed class, called the follicular plus interfollicular pattern, has been introduced. Some of these features are specific to a certain scalp disease, while others can be found in many hair disorders. Although studies suggest that the use of trichoscopy can improve clinical accuracy, further investigation is needed. This review provides update information on the trichoscopic features of the most common scalp disorders, striving to show a histopathological and clinical correlation. PMID- 26160503 TI - The Effects of Petroleum Hydrocarbons on Algae Can Be Reversed in the Presence of a Primary Consumer. AB - The ecotoxicological effects of a mixture of petroleum hydrocarbons were tested on densities of two algae, Platymonas helgolandica var. tsingtaoensis and Isochrysis galbana, and of a rotifer, Brachionus plicatilis, by single-species and customized community experiments. Test concentrations ranged from 0 to 100 mg L(-1), while five to seven treatments were assessed in triplicate within 1 month. A significant decrease in densities during single-species toxicity tests were found when concentrations of petroleum hydrocarbons were above 1.0 mg L(-1). However, equilibrium densities of algae in the customized community showed a different pattern, which increased with concentration and reached a peak at 20.0 mg L(-1). The community-based no observed effect concentration (NOEC; 1.0 mg L( 1)) was different from the NOEC derived by single-species toxic tests (0.25 mg L( 1)). This demonstrates that ecotoxicological effects on plankton as part of a community is significantly different from single-species toxicity tests owing to ecological interactions. PMID- 26160504 TI - Influence of Sedimentation Rate on the Metal Contamination in Sediments of Bohai Bay, China. AB - Metal concentration in marine sediments is influenced by sedimentation rate. In this study, the metal concentration in sediments of Bohai Bay, China, was adjusted by sedimentation rate, which was derived from the radionuclide dating method. The results showed that the sedimentation rate of Bohai Bay sediments increased from 0.3 to 0.55 g/a over time, especially in the last 30 years since the economic reform in China. The sequence of metal concentrations (mg/kg) is: Cr(97.41) > Zn(73.14) > Cu(20.59) > Pb(16.42) > Cd(0.49). Through the adjustment, the change of metal concentration in sediment cores increased obviously from bottom to surface sediments. It indicated that the increasing sedimentation rate of Bohai Bay in recent years diluted the metal concentration in the sediment. PMID- 26160505 TI - Marriage and separation risks among German cohabiters: Differences between types of cohabiter. AB - We propose a typology of different meanings of cohabitation that combines cohabiters' intentions to marry with a general attitude toward marriage, using competing risk analyses to examine whether some cohabiters are more prone than others to marry or to separate. Using data (N = 1,258) from four waves of the German Family Panel (PAIRFAM) and a supplementary study (DEMODIFF), we compared eastern and western German cohabiters of the birth cohorts 1971-73 and 1981-83. Western Germans more frequently view cohabitation as a step in the marriage process, whereas eastern Germans more often cohabit as an alternative to marriage. Taking into account marital attitudes reveals that cohabiters without marriage plans differ from those with plans in their relationship careers, and also shows that cohabiters who plan to marry despite holding a less favourable view of marriage are less likely to realize their plans than cohabiters whose intentions and attitudes are more congruent. PMID- 26160506 TI - High-Concentration Piperine: Capsaicin-Sensitive and -Insensitive Effects on Isolated Organs. AB - Piperine (P), a sensory stimulant in black pepper, is an agonist on TRPV1 receptors. Earlier work has showed capsaicin-sensitive and -insensitive mechanisms of the contractile action of P on the intestine. The current isolated organ study in the guinea-pig ileum, urinary bladder and trachea (a) confirms the presence of such components of effect (ileum and bladder); (b) indicates TRPV1 involvement in the effect of 5 or 30 umol/l of P on the basis of an inhibitory action of the antagonist BCTC (ileum); (c) indicates that HC 030031-sensitive TRPA1 receptors and nifedipine-sensitive Ca(2+) channels contribute to the capsaicin-resistant contraction to 30 umol/l P (ileum) and (d) shows that the contractile effect of P up to 100 umol/l (guinea-pig trachea) or 30 umol/l (guinea-pig urinary bladder) is capsaicin-sensitive and mediated by TRPV1 receptors/channels. PMID- 26160507 TI - Mean Platelet Volume as a Biomarker for Thyroid Carcinoma. AB - : AbstractObjective: This study aimed to determine the relationship between MPV and thyroid malignancy by comparing patients who underwent surgery for benign or malignant thyroid diseases. BACKGROUND: Mean platelet volume (MPV) is a useful early indicator of platelet activation. Platelets differ in terms of functional activity and size. Large platelets are relatively new, more reactive and produce more thrombogenic factors. Therefore, in conditions that involve increased platelet activation, an increase in the proportion of young platelets and MPV is expected. PATIENTS AND METHODS: This study involved 146 patients who underwent total thyroidectomy because of benign (99 patients) or malignant (47 patients) diseases of the thyroid. Data on age, sex, MPV, white blood cell (WBC) count, hemoglobin level and platelet count were collected retrospectively. RESULTS: MPV was significantly higher in patients with malignant thyroid diseases than in those with benign thyroid diseases. Age, sex, hemoglobin level, WBC count and platelet count did not significantly differ between the two groups. CONCLUSION: MPV was significantly higher in patients with thyroid malignancies than in patients with benign thyroid diseases. We propose that MPV might be an important predictive factor for thyroid malignancies. Further prospective studies with a larger number of patients in high-volume endocrine surgery centers are required to confirm our findings. PMID- 26160509 TI - Rumours and prejudice. PMID- 26160511 TI - President's message. Rural generalist medicine: moving forward together. PMID- 26160508 TI - Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics. AB - The type 1 parathyroid hormone receptor (PTH1R) is a key regulator of calcium homeostasis and bone turnover. Here, we employed SILAC-based quantitative mass spectrometry and bioinformatic pathways analysis to examine global changes in protein phosphorylation following short-term stimulation of endogenously expressed PTH1R in osteoblastic cells in vitro. Following 5min exposure to the conventional agonist, PTH(1-34), we detected significant changes in the phosphorylation of 224 distinct proteins. Kinase substrate motif enrichment demonstrated that consensus motifs for PKA and CAMK2 were the most heavily upregulated within the phosphoproteome, while consensus motifs for mitogen activated protein kinases were strongly downregulated. Signaling pathways analysis identified ERK1/2 and AKT as important nodal kinases in the downstream network and revealed strong regulation of small GTPases involved in cytoskeletal rearrangement, cell motility, and focal adhesion complex signaling. Our data illustrate the utility of quantitative mass spectrometry in measuring dynamic changes in protein phosphorylation following GPCR activation. PMID- 26160513 TI - Rural longitudinal integrated clerkships: changing interests and demographics of medical students. AB - INTRODUCTION: The University of Calgary Longitudinal Integrated Clerkship (UCLIC) is an integrated curriculum of at least 32 weeks' duration based in rural communities. Rural LICs have been proposed as a method to respond to the needs of underserved rural communities; therefore, assessing evolving learner interest and demographics over time is of importance to rural communities. METHODS: Three surveys were administered to first-year medical students at the University of Calgary from the classes of 2009, 2010 and 2015. The surveys assessed demographic information as well as interest in and attitudes toward pursuing a rural-based LIC. RESULTS: Overall, 42% of students (76% of decided students) reported that they would consider the rural UCLIC. Between 2009 and 2010, the proportion of students who would not consider the UCLIC decreased from 25% to 8%, and thereafter was maintained at that level. Over the same period, interest among students considering Royal College of Physicians and Surgeons of Canada (RCPSC) specialties significantly increased. Although student attitudes about the value of the LIC were consistently positive, students remained concerned about social considerations. CONCLUSION: There has been an increase in student willingness to consider a rural LIC, most significantly among students interested in RCPSC specialties. Career plans and demographics of students continue to influence their interest in and attitudes toward LICs. PMID- 26160514 TI - Evaluation of an inpatient medical withdrawal program in rural Ontario: a 1-year prospective study. AB - INTRODUCTION: We present a 1-year program evaluation of the Medical Withdrawal Support Service (MWSS) provided at the Sioux Lookout Meno Ya Win Health Centre. The centre's service area includes 4 rural municipalities and 28 First Nations communities. The program involves inpatient detoxification for opioid dependence with the use of buprenorphine-naloxone. METHODS: Data were collected from preadmission interviews (i.e., medical history, substance use history, previous counselling, social history, previous addiction treatment and screening tools used during the interview); discharge forms (i.e., length of stay, maximum dose of prescribed buprenorphine-naloxone and client goals); and postdischarge interviews. RESULTS: Overall, 81% of the clients successfully completed the program. Two weeks after discharge, 48% of clients reported continued abstinence. At 3-month follow-up, 32% were abstinent, and at 6 months, 30% were abstinent. CONCLUSION: The MWSS shows positive outcomes for many clients, their families and communities. Clients returned to work and school, became more engaged in healthy meal preparation and exercise, spent more time with family and were more involved as leaders in their communities. PMID- 26160515 TI - The occasional umbilical venous line. PMID- 26160516 TI - Country cardiograms case 54. PMID- 26160517 TI - Wellens syndrome. PMID- 26160518 TI - Wellens syndrome: The author responds. PMID- 26160519 TI - Country cardiograms case 54: Answer. PMID- 26160520 TI - SEEK: a systems biology data and model management platform. AB - BACKGROUND: Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems biology models. There are a large number of public repositories for storing biological data of a particular type, for example transcriptomics or proteomics, and there are several model repositories. However, this silo-type storage of data and models is not conducive to systems biology investigations. Interdependencies between multiple omics datasets and between datasets and models are essential. Researchers require an environment that will allow the management and sharing of heterogeneous data and models in the context of the experiments which created them. RESULTS: The SEEK is a suite of tools to support the management, sharing and exploration of data and models in systems biology. The SEEK platform provides an access-controlled, web-based environment for scientists to share and exchange data and models for day-to-day collaboration and for public dissemination. A plug in architecture allows the linking of experiments, their protocols, data, models and results in a configurable system that is available 'off the shelf'. Tools to run model simulations, plot experimental data and assist with data annotation and standardisation combine to produce a collection of resources that support analysis as well as sharing. Underlying semantic web resources additionally extract and serve SEEK metadata in RDF (Resource Description Format). SEEK RDF enables rich semantic queries, both within SEEK and between related resources in the web of Linked Open Data. CONCLUSION: The SEEK platform has been adopted by many systems biology consortia across Europe. It is a data management environment that has a low barrier of uptake and provides rich resources for collaboration. This paper provides an update on the functions and features of the SEEK software, and describes the use of the SEEK in the SysMO consortium (Systems biology for Micro-organisms), and the VLN (virtual Liver Network), two large systems biology initiatives with different research aims and different scientific communities. PMID- 26160521 TI - Cytokine responses induced by diesel exhaust particles are suppressed by PAR-2 silencing and antioxidant treatment, and driven by polar and non-polar soluble constituents. AB - Adsorbed soluble organics seem to be the main drivers of inflammatory responses induced by diesel exhaust particles (DEP). The specific compounds contributing to this process and the cellular mechanisms behind DEP-induced inflammation are not well known. We have assessed pro-inflammatory effects of DEP and various soluble DEP fractions, in human bronchial epithelial cells (BEAS-2B). DEP increased the expression of interleukin (IL)-6 and CXCL8. Silencing of the aryl hydrocarbon receptor (AhR) by siRNA or pretreatment with AhR-antagonists did not attenuate DEP-induced IL-6 and CXCL8 responses. However, the halogenated aromatic hydrocarbon (HAH)-selective AhR antagonist CH223191 caused a considerable reduction in DEP-induced CYP1A1 expression indicating that this response may be due to dioxin or dioxin-like constituents in DEP. Knock-down of protease activated receptor (PAR)-2 attenuated IL-6 responses without affecting CXCL8. Antioxidants did not affect IL-6 expression after 4h DEP-exposure and only partly reduced CXCL8 expression. However, after 24h exposure antioxidant treatment partly suppressed IL-6 protein release and completely blocked CXCL8 release. Furthermore, a heptane-soluble (non-polar) extract of DEP induced both IL-6 and CXCL8 release, whereas a PBS-soluble (highly polar) extract induced only IL-6. Thus, pro-inflammatory responses in DEP-exposed epithelial cells appear to be the result of both reactive oxygen species and receptor signaling, mediated through combinatorial effects between both non-polar and polar constituents adhered to the particle surface. PMID- 26160522 TI - Adverse childhood experiences and substance use among Hispanic emerging adults in Southern California. AB - INTRODUCTION: Emerging adults who experienced stressful childhoods may engage in substance use as a maladaptive coping strategy. Given the collectivistic values Hispanics encounter growing up, adverse childhood experiences may play a prominent role in substance use decisions as these events violate the assumptions of group oriented cultural paradigms. Alternatively, adverse childhood events might not increase the risk of substance use because strong family ties could mitigate the potential maladaptive behaviors associated with these adverse experiences. This study examined whether adverse childhood experiences were associated with substance use among Hispanic emerging adults. METHOD: Participants (n = 1420, mean age = 22, 41% male) completed surveys indicating whether they experienced any of 8 specific adverse experiences within their first 18 years of life, and past-month cigarette use, marijuana use, hard drug use, and binge drinking. Logistic regression models examined the associations between adverse childhood experiences and each category of substance use, controlling for age, gender, and depressive symptoms. RESULTS: The number of adverse childhood experiences was significantly associated with each category of substance use. A difference in the number of adverse childhood experiences, from 0 to 8, was associated with a 22% higher probability of cigarette smoking, a 24% higher probability of binge drinking, a 31% higher probability of marijuana use, and a 12% higher probability of hard drug use respectively. CONCLUSIONS: These findings should be integrated into prevention/intervention programs in hopes of quelling the duration and severity of substance use behaviors among Hispanic emerging adults. PMID- 26160523 TI - Quantifying alcohol consumption: Self-report, transdermal assessment, and prediction of dependence symptoms. AB - Research on alcohol use depends heavily on the validity of self-reported drinking. The present paper presents data from 647 days of self-monitoring with a transdermal alcohol sensor by 60 young adults. We utilized a biochemical measure, transdermal alcohol assessment with the WrisTAS, to examine the convergent validity of three approaches to collecting daily self-report drinking data: experience sampling, daily morning reports of the previous night, and 1-week timeline follow-back (TLFB) assessments. We tested associations between three pharmacokinetic indices (peak concentration, area under the curve (AUC), and time to reach peak concentration) derived from the transdermal alcohol signal and within- and between- person variation in alcohol dependence symptoms. The WrisTAS data corroborated 85.74% of self-reported drinking days based on the experience sampling data. The TLFB assessment and combined experience sampling and morning reports agreed on 87.27% of drinking days. Drinks per drinking day did not vary as a function of wearing or not wearing the sensor; this indicates that participants provided consistent reports of their drinking regardless of biochemical verification. In respect to self-reported alcohol dependence symptoms, the AUC of the WrisTAS alcohol signal was associated with dependence symptoms at both the within- and between- person level. Furthermore, alcohol dependence symptoms at baseline predicted drinking episodes characterized in biochemical data by both higher peak alcohol concentration and faster time to reach peak concentration. The results support the validity of self-report alcohol data, provide empirical data useful for optimal design of daily process sampling, and provide an initial demonstration of the use of transdermal alcohol assessment to characterize drinking dynamics associated with risk for alcohol dependence. PMID- 26160524 TI - The utility of collateral student drinking reports: Evidence from a biomarker study. AB - INTRODUCTION: Researchers have increasingly used collateral informants to validate the reports provided by primary research subjects. We assessed the utility of collateral informants for college students in a study that incorporates biomarkers to validate student reports of recent drinking behavior. METHODS: Students from a Midwestern university were randomly selected for a study in which they provided 90-day Timeline Followback data, hair and fingernail specimens for ethylglucuronide (EtG) testing, and information about collateral (friends or peers) informants who were familiar with their drinking behavior. We compared summary measures of recent drinking to collateral informant reports for the subset of 72 students who were selected to participate in the collateral validation process who had complete measures. Kappa, weighted kappa, and McNemar tests were performed to evaluate levels of agreement. We compared levels of use indicated by each informant within the context of EtG findings. We also compared respondent and collateral reports with respect to heavy drinking directly to EtG test results. RESULTS: There was considerable overlap between the reports provided by the student participants and their collateral informants. Within the context of EtG-informed analyses, collaterals rarely provided new information about heavy use beyond that provided by the study subjects. CONCLUSIONS: Collateral informants have limited utility in non-clinical studies of heavy drinking in randomly selected college students. PMID- 26160525 TI - Therapeutic benefit of melatonin in refractory central serous chorioretinopathy. AB - PURPOSE: To evaluate the efficacy and safety of melatonin for the treatment of chronic central serous chorioretinopathy (CSCR). METHODS: Prospective comparative case series. A total of 13 patients with chronic CSCR were treated for 1 month: 8 patients were treated orally with 3 mg melatonin t.i.d., and 5 with placebo. All patients had 20/40 or worse Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) in the affected eye or presented an incapacitating scotoma. Most of the patients had previous failed treatments for their condition. Observational procedures included ETDRS BCVA, and complete ophthalmic examination. Optical coherence tomography (OCT) was performed at day 1 and week 4. Fluorescein angiography was performed at baseline only for diagnostic purposes. Data were subjected to two-sample t-test statistical analysis. P-values of <0.05 were considered statistically significant. RESULTS: At 1-month follow up, BCVA significantly improved in 87.5% of patients treated with melatonin (7 of 8 patients, P<0.05). All patients showed a mean significant reduction (P<0.01) of central macular thickness (CMT) when compared with the baseline, with 3 patients (37.5%) exhibiting complete resolution of subretinal fluid at 1-month follow-up. No significant side effects were observed. No changes in BCVA or CMT were noted in the control group. CONCLUSIONS: These results suggest that melatonin is safe, well tolerated, and effective in the treatment of chronic CSCR, as it significantly improved BCVA and CMT in patients with this pathology. Further evaluations with longer follow-up and a larger patient population are desirable. PMID- 26160527 TI - The effectiveness of asking multiple questions at the Royal College of Ophthalmologists Annual Congress. PMID- 26160526 TI - Three percent diquafosol ophthalmic solution as an additional therapy to existing artificial tears with steroids for dry-eye patients with Sjogren's syndrome. AB - PURPOSE: To investigate the long-term results of 3% diquafosol ophthalmic solution as an alternative therapy to existing ophthalmic solutions, including topical immunosuppression, for the treatment of dry eye in patients with Sjogren's syndrome. METHODS: This study involved 14 female dry-eye patients (mean age: 62.4 years) with Sjogren's syndrome who insufficiently responded to their current therapy. In all patients, 3% diquafosol ophthalmic solution was administered six times daily for 12 months in substitution for artificial tears and sodium hyaluronate ophthalmic solution. Their use of corticosteroid eye drops remained unchanged from that prior to the treatment with diquafosol sodium. The subjective symptoms assessed, and ocular signs including tear meniscus radius and the tear film breakup time, and ocular-surface epithelial damage score were examined at 1, 2, 3, 4, 5, 6, 9, and 12 months after initiating treatment. RESULTS: Among the subjective symptoms, significant improvement was obtained in dryness at 2 months post treatment, in eye fatigue at 1, 2, 3, 4, and 12 months post treatment, and in pain at 1, 2, 6, and 12 months post treatment. Difficulty in opening the eye, foreign body sensation, and redness were also significantly ameliorated at various time-points. The tear meniscus radius and the tear film breakup time were significantly improved throughout the observation period, and the corneal epithelial staining scores were significantly decreased at 3 months post treatment. CONCLUSIONS: In dry-eye patients with Sjogren's syndrome, treatment with 3% diquafosol ophthalmic solution improved both symptoms and signs, and that effectiveness was maintained for 12 months. PMID- 26160528 TI - Intra-silicone oil injection of methotrexate at the end of vitrectomy for advanced proliferative diabetic retinopathy. AB - PURPOSE: To evaluate the role of methotrexate (MTX) injected into the silicone oil at the end of pars plana vitrectomy for advanced proliferative diabetic retinopathy (PDR). METHODS: In this prospective comparative interventional study, eyes with severe diabetic tractional macular detachment or combined tractional/rhegmatogenous retinal detachment were included. Standard 20 gauge pars plana vitrectomy, and retinal reattachment was performed. In the case group, 250 MUg MTX was injected into the silicone oil at the end of surgery. The rate of retinal re-detachment associated with fibrovascular proliferation or proliferative vitreoretinopathy (PVR) was assessed. RESULTS: Overall, 38 eyes of 35 patients (19 cases and 19 controls) were studied. The two groups were matched for age, sex, preoperative visual acuity, and the type of surgery (vitrectomy alone vs combined phacoemulsification/vitrectomy). Retinal re-detachment with fibrovascular proliferation or PVR occurred in seven eyes (36.8%) in the MTX group and eight eyes (42.1%) in the control group (P = 0.74). Mean change in visual acuity was 0.04 +/- 0.71 and 0.39 +/- 0.70 logMAR in the MTX and the control group, respectively (P = 0.14). The rate of improvement or worsening of visual acuity was similar between the two groups (P = 0.51 and P = 0.12). CONCLUSION: Intra-silicone injection of MTX at the end of vitrectomy for retinal detachment associated with severe PDR did not reduce the risk of postoperative retinal detachment due to the fibrous or fibrovascular proliferations. PMID- 26160530 TI - Role of miotics and cycloplegics in angle closure. PMID- 26160529 TI - Dementia is associated with open-angle glaucoma: a population-based study. AB - PURPOSE: Previous epidemiologic studies that focused on the association between open-angle glaucoma (OAG) and dementia showed inconsistent results. In the present study, we explored the association between OAG and dementia in an ethnic Chinese (i.e., Taiwanese) population using a population-based data set. METHODS: We retrieved data on study subjects for this case-control study from the Longitudinal Health Insurance Database 2000. We identified 7770 patients who had a diagnosis of dementia as cases, and 7770 subjects matched in terms of sex and age, which were randomly extracted as controls. A conditional logistic regression conditioned on age group, sex, and index year was used to assess the association of dementia with previously diagnosed OAG among the sampled patients. RESULTS: Of 15,540 patients, 1.70% had prior OAG, including 2.02% of the dementia group and 1.38% of the controls. After adjusting for patient socioeconomic characteristics and comorbid medical disorders, dementia patients were more likely to have had prior OAG than controls (odds ratio (OR): 1.44; 95% confidence interval (CI): 1.12-1.85; P<0.01). In addition, female dementia patients were more likely to have had prior OAG than controls (OR: 1.93; 95% CI: 1.35-2.77; P<0.001), whereas no statistical difference in prior OAG between male dementia patients and controls was found. CONCLUSIONS: Female dementia patients were associated with a higher proportion of prior OAG than were the controls. PMID- 26160531 TI - Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma. AB - AIM: To present our experience of the use of stereotactic radiosurgery and proton beam therapy to treat posterior uveal melanoma over a 10 year period. METHODS AND MATERIALS: Case notes of patients treated with stereotactic radiosurgery (SRS), or Proton beam therapy (PBT) for posterior uveal melanoma were reviewed. Data collected included visual acuity at presentation and final review, local control rates, globe retention and complications. We analysed post-operative visual outcomes and if visual outcomes varied with proximity to the optic nerve or fovea. RESULTS: 191 patients were included in the study; 85 and 106 patients received Stereotactic radiosurgery and Proton beam therapy, respectively. Mean follow up period was 39 months in the SRS group and 34 months in the PBT group. Both treatments achieved excellent local control rates with eye retention in 98% of the SRS group and 95% in the PBT group. The stereotactic radiosurgery group showed a poorer visual prognosis with 65% losing more than 3 lines of Snellen acuity compared to 45% in the PBT group. 33% of the SRS group and 54% of proton beam patients had a visual acuity of 6/60 or better. CONCLUSIONS: Stereotactic radiosurgery and proton beam therapy are effective treatments for larger choroidal melanomas or tumours unsuitable for plaque radiotherapy. Our results suggest that patients treated with proton beam therapy retain better vision post operatively; however, possible confounding factors include age, tumour location and systemic co-morbidities. These factors as well as the patient's preference should be considered when deciding between these two therapies. PMID- 26160533 TI - Response to 'Role of miotics and cycloplegics in angle closure'. PMID- 26160534 TI - The Little Penguin (Eudyptula minor) as an indicator of coastal trace metal pollution. AB - Monitoring trace metal and metalloid concentrations in marine animals is important for their conservation and could also reliably reflect pollution levels in their marine ecosystems. Concentrations vary across tissue types, with implications for reliable monitoring. We sampled blood and moulted feathers of the Little Penguin (Eudyptula minor) from three distinct colonies, which are subject to varying levels of anthropogenic impact. Non-essential trace metal and metalloid concentrations in Little Penguins were clearly linked to the level of industrialisation adjacent to the respective foraging zones. This trend was more distinct in blood than in moulted feathers, although we found a clear correlation between blood and feathers for mercury, lead and iron. This study represents the first reported examination of trace metals and metalloids in the blood of any penguin species and demonstrates that this high trophic feeder is an effective bioindicator of coastal pollution. PMID- 26160535 TI - Outcome of Isolated Premature Menarche: A Retrospective and Follow-Up Study. AB - BACKGROUND AND AIMS: Isolated premature menarche is isolated or recurrent vaginal bleeding in a female in the absence of appropriate secondary sexual characters. METHODS: Retrospective chart review of patients with premature menarche, followed by a telephone questionnaire. Charts of patients evaluated in the Pediatric Endocrine Clinic for premature vaginal bleeding from 1982-2013 were reviewed. RESULTS: Of 21 patients identified, 17 could be contacted. Five newly diagnosed patients were recruited during the course of the study. The median age at initial presentation was 7 years. Most patients presented with Tanner I sexual development. Some had more advanced breast staging, which regressed later. All had prepubertal baseline and stimulated gonadotropins. Most of the patients reported a single or few episodes of menses. Two reported continuation of irregular bleeding into adulthood. All reported an adult height within the midparental target height. CONCLUSION: Premature menarche in the absence of other appropriate secondary sexual characteristics is a benign entity. Most patients have a few isolated episodes of menses that stop spontaneously; some may continue to have periods into adulthood. Unlike true puberty, these patients do not demonstrate advanced skeletal maturation, and the adult height is normal. Fertility appears to be normal. PMID- 26160536 TI - Response Bias on Self-Report Measures of Sexual Fantasies Among Sexual Offenders. AB - The impact of sexual fantasies in future risk and treatment response among sexual offenders has long been known. However, as we develop objective self-report measures of sexual fantasies, response bias is becoming an increasing concern. In examining a sample of institutionalized sex offenders, the present study suggests that offenders' responses on these measures are prone to response bias, the bias does not negate their associations with other self-report measures of sexual deviance, and relationship of their sexual fantasies does not appear to relate to actual behavioral indications. Clinical and research implications for these findings are discussed. PMID- 26160532 TI - Pattern recognition receptors in microbial keratitis. AB - Microbial keratitis is a significant cause of global visual impairment and blindness. Corneal infection can be caused by a wide variety of pathogens, each of which exhibits a range of mechanisms by which the immune system is activated. The complexity of the immune response to corneal infection is only now beginning to be elucidated. Crucial to the cornea's defences are the pattern-recognition receptors: Toll-like and Nod-like receptors and the subsequent activation of inflammatory pathways. These inflammatory pathways include the inflammasome and can lead to significant tissue destruction and corneal damage, with the potential for resultant blindness. Understanding the immune mechanisms behind this tissue destruction may enable improved identification of therapeutic targets to aid development of more specific therapies for reducing corneal damage in infectious keratitis. This review summarises current knowledge of pattern-recognition receptors and their downstream pathways in response to the major keratitis causing organisms and alludes to potential therapeutic approaches that could alleviate corneal blindness. PMID- 26160537 TI - Examining the Continuity of Juvenile Sex Offending Into Adulthood and Subsequent Patterns of Sex and General Recidivism. AB - Current sex offending legislation and public opinion present an image of sexual offenders as specialized predators who are likely to exhibit continued sexually deviant behavior over the life-course. Although sex offending continuity and post release recidivism has been independently assessed in prior research, the potential link between sex offending continuity and post-release recidivism has yet to be investigated. Using data collected at two different time points from a sample of sex offenders who served a prison sentence for an adult sex offense, the present study examines the prevalence of sex offending continuity, and its potential linkages with subsequent sex and general recidivism as well as identifying risk factors related to these outcomes. The multivariate results indicate a low rate of sex offending continuity in general but suggest the presence of identifiable risk factors that predict sex offending continuity. Specifically, non-sexual juvenile offending is the most notable of the numerous risk factors found to be associated with those displaying sex offending continuity from adolescence into adulthood. Subsequent analyses also reveal a significant association between sex offending continuity and sexual recidivism but not general recidivism. Policy implications, study limitations, and directions for future research are also discussed. PMID- 26160538 TI - Association of toll-like receptors with susceptibility to tuberculosis suggests sex-specific effects of TLR8 polymorphisms. AB - BACKGROUND: Toll-like receptors (TLRs) are involved in the recognition of conserved microbial structures, leading to activation of an inflammatory response and formation of an adaptive immune response. METHODS: Twenty-three polymorphisms in five TLR genes were genotyped in 729 tuberculosis cases and 487 healthy controls in a population-based case-control association study in a South African population. RESULTS: We detected sex-specific associations for TLR8 polymorphisms, with rs3761624 (OR=1.54, p<0.001), rs3764879 (OR=1.41, p=0.011) and rs3764880 (OR=1.42, p=0.011) associated in females and rs3764879 (OR=0.72, p=0.013) and rs3764880 (OR=0.75, p=0.036) associated in males. Epistatic interactions between the TLR genes were investigated and the TLR1_rs4833095 polymorphism was shown to interact with TLR2_rs3804100 and (GT)n microsatellite (p=0.002) and alter susceptibility to TB. We also studied the role of TLRs in disease caused by different Mycobacterium tuberculosis genotypes in 257 tuberculosis cases, and identified associations between specific TLR polymorphisms and disease caused by specific strains. CONCLUSION: This study provides further evidence that the TLRs play an important role in the outcome of tuberculosis disease, and suggests a partial explanation for the male bias in tuberculosis ratios. PMID- 26160539 TI - High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil. AB - Trichomonas vaginalis is the etiological agent of trichomoniasis, the most common non-viral sexually transmitted disease (STD) in world, with 276.4 million new cases each year. T. vaginalis can be naturally infected with Mycoplasma hominis and Trichomonasvirus species. This study aimed to evaluate the prevalence of T. vaginalis infected with four distinct T. vaginalis viruses (TVVs) and M. hominis among isolates from patients in Porto Alegre city, South Brazil. An additional goal of this study was to investigate whether there is association between metronidazole resistance and the presence of M. hominis during TVV infection. The RNA expression level of the pyruvate ferredoxin oxidoreductase (PFOR) gene was also evaluated among metronidazole-resistant and metronidazole-sensitive T. vaginalis isolates. A total of 530 urine samples were evaluated, and 5.7% samples were positive for T. vaginalis infection. Among them, 4.51% were isolated from female patients and 1.12% were from male patients. Remarkably, the prevalence rates of M. hominis and TVV-positive T. vaginalis isolates were 56.7% and 90%, respectively. Most of the T. vaginalis isolates were metronidazole-sensitive (86.7%), and only four isolates (13.3%) were resistant. There is no statistically significant association between infection by M. hominis and infection by TVVs. Our results refute the hypothesis that the presence of the M. hominis and TVVs is enough to confer metronidazole resistance to T. vaginalis isolates. Additionally, the role of PFOR RNA expression levels in metronidazole resistance as the main mechanism of resistance to metronidazole could not be established. This study is the first report of the T. vaginalis infection by M. hominis and TVVs in a large collection of isolates from South Brazil. PMID- 26160540 TI - Trichoderma viride induces pathogenesis related defense response against rot pathogen infection in groundnut (Arachis hypogaea L.). AB - The study examine induction of defense enzymes involved in phenylpropanoid pathway and accumulation of pathogenesis related proteins in rot pathogen (Aspergillus niger Van Tieghem) challenged groundnut seedlings in response to Trichoderma viride JAU60. Seeds of five groundnut varieties differing in collar rot susceptibility were sown under non-infested, pathogen infested and pathogen+T. viride JAU60 seed treatment. Collar rot disease evident between 31.0% (J-11, GG-2) and 67.4% (GG-20) in different groundnut varieties under pathogen infested which was significantly reduced from 58.1% (J-11, GG-2) to 51.6% (GG-20) by Trichoderma treatment. The specific activities of polyphenol oxidase (EC 1.14.18.1) and beta-1,3 glucanase (EC 3.2.1.6) elevated 3.5 and 2.3-fold, respectively, at 3 days; phenylalanine ammonia lyase (EC 4.3.1.5) evident 1.6 fold higher at 6 days; and chitinase (EC 3.2.1.14) sustained 2.3-2.8 folds up to 9 days in Trichoderma treated+pathogen infested seedlings of tolerant varieties (J-11, GG-2) compared with moderate and susceptible (GAUG-10, GG-13, GG-20). T. viride JAU60 induces defense enzymes in a different way for tolerant and susceptible varieties to combat the disease. This study indicates the synergism activation of defense enzymes under the pathogenic conditions or induced resistance by T. viride JAU60 in a different groundnut varieties susceptible to collar rot disease. PMID- 26160541 TI - Insights of the genetic diversity of DENV-1 detected in Brazil in 25 years: Analysis of the envelope domain III allows lineages characterization. AB - Dengue virus type 1 (DENV-1) was first isolated in Brazil in 1986 in the state of Rio de Janeiro (RJ) and during 25years, this serotype emerged and re-emerged causing explosive epidemics in the country. Here, we aimed to present the phylogeny and molecular characterization based on the envelope gene (E) of DENV-1 (n=48) isolated during epidemics occurred from 1986 to 2011. Six full coding region genomes of DENV-1 were fully sequenced and possible genomic recombination events were analyzed. The results showed that the Brazilian DENV-1 isolates analyzed belong to genotype V (Americas/Africa), but grouping into distinct clades. Three groups were identified, one dating from 1986 to 2002 (lineage 1a), a second group isolated from 2009 to 2011 and a representative strain isolated in 2002 (lineage 2), and a group of strains isolated from 2010 to 2011 (lineage 1b). The lineages 1a and 1b were more closely related to the American strains, while lineage 2 to the Asian strains. Amino acids (aa) substitutions were observed in the domains I and III of the E protein and were associated to the lineages segregation. A substitution on E297 differentiated the lineage 1a from the lineages 1b and 2. Substitutions on E338, E394 (domain III), E428 and E436 (stem region) differentiated lineages 1a, 1b and 2. With the exception of the C gene, all the others genes analyzed allowed the DENV-1 classification into the distinct genotypes. Interestingly, the E gene's domain III and stem regions alone were able to characterize the distinct lineages, as observed by the analysis of the entire E gene and the complete coding region. No recombinant events were detected, but a strain belonging to lineage 1a was closely related to a known recombinant strain (AF513110/BR/2001). PMID- 26160542 TI - Phylogenetic study reveals co-circulation of Asian II and Cosmopolitan genotypes of Dengue virus serotype 2 in Nepal during 2013. AB - The re-emergence of dengue virus in Nepal and the recent widespread disease epidemics of unprecedented magnitude have raised a great public health concern. There are very few reports on Dengue virus (DENV) strains circulating in the country, especially at the molecular phylogenetics level. In this study, clinical samples from an outbreak in Nepal in 2013, which were positive for DENV serotype 2, were characterized by targeted genome sequencing. Envelope protein (E) coding region from fifteen samples were sequenced and compared with DENV-2 sequences of strains from different geographic regions obtained from the GenBank. Compared to the prototype New Guinea C strain, the samples had a total of eleven non synonymous substitutions in the envelope protein coding region leading to amino acid change at positions 47, 52, 71, 126, 129, 149, 164, 390, 402, 454 and 462. However, none of these sites were found to be positively selected. A major observation was the presence of two distinct genotypes (Cosmopolitan Genotype IVa and Asian II) in the outbreak as seen by the phylogenetic analysis. It gives the first evidence of the introduction of Cosmopolitan Genotype IVa in Nepal. These strains replace the Genotype IVb strains prevalent earlier since 2004. Both genotypes had closer genetic relation to strains from other countries indicating possibility of exotic introduction. The Genotype IVa strain seems to be more adapted in C6/36 mosquito cells as indicated by its marginally increased replication rate than the Asian II strain in in vitro infection kinetics assays. The genotype replacement and co-circulation of two distinct genotypes may have significant consequences in dengue epidemiology and disease dynamics in Nepal in years to come. PMID- 26160543 TI - High-level of viral genomic diversity in cervical cancers: A Brazilian study on human papillomavirus type 16. AB - Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention. PMID- 26160544 TI - Genetic diversity of Brucella abortus and Brucella melitensis in Kazakhstan using MLVA-16. AB - Brucellosis is an endemic disease in Central Asia characterized by high infection rates in humans and animals. Currently, little is known about the genetic diversity of Brucella spp. circulating in the region, despite the high prevalence of brucellosis. This study aimed to analyze the genetic diversity of Brucella melitensis and Brucella abortus strains circulating in the Republic of Kazakhstan. We genotyped 128 B. melitensis and 124 B. abortus strains collected in regions with the highest prevalence of brucellosis. Genotyping was performed using multi-locus variable-number tandem-repeat analysis (MLVA). Analysis of a subset of 8 loci (MLVA-8) of 128 B. melitensis strains identified genotypes 42 (n=108), 43 (n=2), and 63 (n=19) related to the 'East Mediterranean' group. An MLVA-16 assay sorted 128 B. melitensis strains into 25 different genotypes. Excluding one variable locus, MLVA-15 of B. melitensis was distinct from strains originating in the Mediterranean region; however, 77% of them were identical to strains isolated in China. A minimum spanning tree for B. melitensis using MLVA 15 analysis clustered the local strains together with strains previously collected in China. MLVA-8 analysis of 124 B. abortus strains identified them as genotype 36, suggesting Eurasian distribution of this lineage. Complete MLVA-16 assay analysis clustered the strains into five genotypes, revealing little diversity of B. abortus when compared on the global scale. A minimum spanning tree for B. abortus obtained using MLVA-15 analysis clustered the 2 most prevalent genotypes (n=117) together with strains previously collected in China. Thus, MLVA analysis was used to characterize 252 strains of Brucella collected in Kazakhstan. The analysis revealed genetic homogeneity among the strains. Interestingly, identical MLVA-15 profiles were found in seemingly unrelated outbreaks in China, Turkey, and Kazakhstan. Further analysis is needed for better understanding of the epidemiology of brucellosis in Asia. PMID- 26160545 TI - Investigation of the morphological diversity of the potentially zoonotic Trypanosoma copemani in quokkas and Gilbert's potoroos. AB - Trypanosomes are blood-borne parasites that can cause severe disease in both humans and animals, yet little is known of the pathogenicity and life-cycles of trypanosomes in native Australian mammals. Trypanosoma copemani is known to be infective to a variety of Australian marsupials and has recently been shown to be potentially zoonotic as it is resistant to normal human serum. In the present study, in vivo and in vitro examination of blood and cultures from Australian marsupials was conducted using light microscopy, immunofluorescence, scanning electron microscopy and fluorescence in situ hybridization. Promastigote, sphaeromastigote and amastigote life-cycle stages were detected in vivo and in vitro. Novel trypanosome-like stages were also detected both in vivo and in vitro representing an oval stage, an extremely thin stage, an adherent stage and a tiny round stage. The tiny round and adherent stages appeared to adhere to erythrocytes causing potential haematological damage with clinical effects similar to haemolytic anaemia. The present study shows for the first time that trypomastigotes are not the only life-cycle stages circulating within the blood stream of trypanosome infected Australian native marsupials and provides insights into possible pathogenic mechanisms of this potentially zoonotic trypanosome species. PMID- 26160546 TI - Optical detection enhancement in porous volumetric microfluidic capture elements using refractive index matching fluids. AB - Porous volumetric capture elements in microfluidic sensors are advantageous compared to planar capture surfaces due to higher reaction site density and decreased diffusion lengths that can reduce detection limits and total assay time. However a mismatch in refractive indices between the capture matrix and fluid within the porous interstices results in scattering of incident, reflected, or emitted light, significantly reducing the signal for optical detection. Here we demonstrate that perfusion of an index-matching fluid within a porous matrix minimizes scattering, thus enhancing optical signal by enabling the entire capture element volume to be probed. Signal enhancement is demonstrated for both fluorescence and absorbance detection, using porous polymer monoliths in a silica capillary and packed beds of glass beads within thermoplastic microchannels, respectively. Fluorescence signal was improved by a factor of 3.5* when measuring emission from a fluorescent compound attached directly to the polymer monolith, and up to 2.6* for a rapid 10 min direct immunoassay. When combining index matching with a silver enhancement step, a detection limit of 0.1 ng mL(-1) human IgG and a 5 log dynamic range was achieved. The demonstrated technique provides a simple method for enhancing optical sensitivity for a wide range of assays, enabling the full benefits of porous detection elements in miniaturized analytical systems to be realized. PMID- 26160547 TI - Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1. AB - AIMS: YchF/Ola1 are unconventional members of the universally conserved GTPase family because they preferentially hydrolyze ATP rather than GTP. These ATPases have been associated with various cellular processes and pathologies, including DNA repair, tumorigenesis, and apoptosis. In particular, a possible role in regulating the oxidative stress response has been suggested for both bacterial and human YchF/Ola1. In this study, we analyzed how YchF responds to oxidative stress and how it potentially regulates the antioxidant response. RESULTS: Our data identify a redox-regulated monomer-dimer equilibrium of YchF as a key event in the functional cycle of YchF. Upon oxidative stress, the oxidation of a conserved and surface-exposed cysteine residue promotes YchF dimerization, which is accompanied by inhibition of the ATPase activity. No dimers were observed in a YchF mutant lacking this cysteine. In vitro, the YchF dimer is dissociated by thioredoxin 1 (TrxA) and this stimulates the ATPase activity. The physiological significance of the YchF-thioredoxin 1 interaction was demonstrated by in vivo cross-linking, which validated this interaction in living cells. This approach also revealed that both the ATPase domain and the helical domain of YchF are in contact with TrxA. INNOVATION: YchF/Ola1 are the first redox-regulated members of the universally conserved GTPase family and are inactivated by oxidation of a conserved cysteine residue within the nucleotide-binding motif. CONCLUSION: Our data provide novel insights into the regulation of the so far ill-defined YchF/Ola1 family of proteins and stipulate their role as negative regulators of the oxidative stress response. PMID- 26160549 TI - Intermittent daytime mouthpiece ventilation successfully augments nocturnal non invasive ventilation, controlling ventilatory failure and maintaining patient independence. AB - A 53-year-old woman with spinal muscular atrophy and a 7-year history of nocturnal non-invasive ventilation (NIV) use via nasal mask and chinstrap was admitted electively. Outpatient review suggested symptomatic hypercapnia and hypoxaemia. Use of her usual NIV resulted in early morning respiratory acidosis due to excess mouth leak, and continuous face mask NIV was instigated while in hospital. Once stabilised, she elected to return to nasal ventilation. At outpatient review, respiratory acidosis reoccurred despite diurnal use of NIV. Using the patient's routine ventilator and a novel mouthpiece and trigger algorithm, intermittent daytime mouthpiece ventilation (MPV) was introduced alongside overnight NIV. Control of respiratory failure was achieved and, vitally, independent living maintained. Intermittent MPV was practicable and effective where the limits of ventilator tolerance had otherwise been reached. MPV may reduce the need for tracheostomy ventilation and this case serves as a reminder of the increasing options routinely available to NIV clinicians. PMID- 26160548 TI - The role of digestive factors in determining glycemic response in a multiethnic Asian population. AB - PURPOSE: There are wide inter-individual differences in glycemic response (GR). We aimed to examine key digestive parameters that influence inter-individual and ethnic differences in GR in healthy Asian individuals. METHODS: Seventy-five healthy male subjects (25 Chinese, 25 Malays, and 25 Asian-Indians) were served equivalent available carbohydrate amounts (50 g) of jasmine rice (JR) and basmati rice (BR) on separate occasions. Postprandial blood glucose concentrations were measured at fasting (-5 and 0 min) and at 15- to 30-min interval over 180 min. Mastication parameters (number of chews per mouth and chewing time per mouthful), saliva alpha-amylase activity, AMY1 gene copy numbers and gastric emptying rate were measured to investigate their relationships with GR. RESULTS: The GR for jasmine rice was significantly higher than for basmati rice (P < 0.001). The median number of AMY1 gene copies was 6, with a range of 2-15. There was a significant positive relationship between AMY1 copy number and alpha-amylase activity (P = 0.002). There were no significant ethnic differences in GR. For both rice varieties, the number of chews per mouthful was positively associated with the GR (JR, P = 0.011; BR, P = 0.005), while chewing time per mouthful showed a negative association (JR, P = 0.039; BR, P = 0.016). Ethnicity, salivary alpha-amylase activity, particle size distribution, gastric emptying rate and AMY1 gene copy numbers were not significant contributors to GR (P > 0.05). CONCLUSION: Mastication parameters contribute significantly to GR. Eating slowly and having larger food boluses before swallowing (less chewing), both potentially modifiable, may be beneficial in glycemic control. PMID- 26160550 TI - Sarcoidosis-related hypercalcaemia due to production of parathyroid hormone related peptide. AB - Hypercalcaemia is frequently observed in patients with sarcoidosis. This is classically attributed to ectopic production of 1,25 dihydroxy vitamin D by sarcoid granulomas. We present a case of sarcoidosis-related hypercalcaemia with normal vitamin D levels. In this patient, production of parathyroid hormone related peptide (PTHrp) was the cause for sarcoidosis-induced hypercalcaemia. As such, plasma PTHrp levels were increased and bone marrow granulomas stained positively for PTHrp expression. Medium-dose prednisolone treatment improved symptoms of sarcoidosis and normalised serum calcium, and PTHrp concentrations. Thus, production of PTHrp may be the cause for hypercalcaemia in some patients with sarcoidosis. PMID- 26160551 TI - c.1437G>A intron 9 substitution on acid alpha-glucosidase gene associated with classic infantile-onset Pompe disease phenotype. AB - Pompe disease, or glycogen storage disease type II (GSD2), an autosomal recessive disease first described by Joannes Cassianus Pompe (1901-1945), causes deficient activity of acid alpha-glucosidase (GAA) enzyme. GAA catalyses alpha 1,4 and alpha 1,6 glucosidic linkages in lysosomes; destruction of these linkages permits glycogen to be separated into glucose and later used for energy. Without proper function of this enzyme, glycogen accumulates in lysosome, causing muscle hypotonia. We report a previously undescribed association of c.1437G>A intron 9 substitution on the GAA gene with severe infantile-onset Pompe disease in a deceased proband and carrier status in four of five surviving family members. Previous authors have found late-onset or moderate severity infantile-onset Pompe disease associated with this allelic variation. Our proband's family's village was suspicious for locally endemic disease. While our proband developed all features of classic infantile onset GSD2, socioeconomic and geographic factors initially suggested an infectious aetiology. PMID- 26160552 TI - Isolated pancreatic cysticercal cyst presenting as a diagnostic challenge: diagnosis and treatment review. AB - Human cysticercosis most commonly affects the subcutaneous tissues, skeletal muscles, lungs, brain, eyes, liver and, rarely, the heart, thyroid and pancreas. Owing to vague clinical presentation and unfamiliarity of clinicians with this entity, it is difficult to diagnosis when seen as an isolated cyst. We present a case of a 16-year-old boy who presented with an upper abdominal lump and jaundice. Ultrasonography (USG) and MRI of the abdomen were carried out, which revealed a cystic mass (8.5 * 7 * 7 cm) in the pancreas. No evidence of solid component or papillary projections was noted within the lesion. Tumour markers carcinoembryonic antigen (CEA) and cancer antigen (CA 19-9) were normal. Fine needle aspiration cytology was performed, which revealed the presence of cysticercus larvae, along with a foreign body giant cell reaction. The patient was treated with therapeutic aspiration and antihelminthic therapy. Since then, he has been symptom free and under regular follow-up for the last 1 year. A diagnosis of cysticercal cyst at atypical sites is very rare and depends mainly on histopathological examination, which, along with USG and MRI, can give an accurate analysis. These cysts can be very well treated non-surgically with antihelminthics and aspiration. PMID- 26160553 TI - Tuberculous 'lock jaw'. PMID- 26160554 TI - Disseminated cysticercosis: whole body MRI. PMID- 26160555 TI - Use of Drosophila in the investigation of sleep disorders. AB - Genetic underpinnings for sleep disorders in humans remain poorly identified, investigated and understood. This is due to the inherent complexity of sleep and a disruption of normal sleep parameters in a number of neurological disorders. On the other hand, there have been steady and remarkable developments in the investigation of sleep using model organisms such as Drosophila. These studies have illuminated conserved genetic pathways, neural circuits and intra-cellular signaling modules in the regulation of sleep. Additionally, work in model systems is beginning to clarify the role of the circadian clock and basal sleep need in this process. There have also been initial efforts to directly model sleep disorders in flies in a few instances where a genetic basis has been suspected. Here, we discuss the opportunities and limitations of studying sleep disorders in Drosophila and propose that a greater convergence of basic sleep research in model organisms and human genetics should catalyze better understanding of sleep disorders and generate viable therapeutic options. PMID- 26160556 TI - Topical antimicrobial photodynamic therapy improves angiogenesis in wounds of diabetic mice. AB - We report the results of our investigations on the effect of antimicrobial photodynamic therapy (APDT) on angiogenesis in wounds of diabetic mice. For this, measurements were made on levels of nitric oxide (NO), vascular endothelial growth factor-A (VEGF-A), and markers of proinflammatory stress (phosphorylated nuclear factor kappa B and p(38) mitogen-activated protein kinase) on day 3 post wounding. For uninfected and infected wounds, the levels of NO, VEGF-A were lower and the levels of phospho-NF-kB-p65, phospho-p(38)MAPK were higher in diabetic mice compared with that in nondiabetic mice. For infected wounds, multiple APDT (fluence ~60 J/cm(2)) led to increase in NO, VEGF-A levels and a decrease in the phospho-NF-kB-p65, phospho-p(38)MAPK. Further, compared with aminoguanidine, and silver nitrate, multiple APDT was observed to result in a much improved proangiogenic response. PMID- 26160558 TI - Photo, pH, and thermo triple-responsive spiropyran-based copolymer nanoparticles for controlled release. AB - A spiropyran-based amphiphilic random copolymer was synthesized and self assembled into photo-, pH-, and thermo-responsive micellar nanoparticles. The triple-stimuli triggered morphological changes of the nanoparticles were revealed by TEM and DLS. Highly efficient controlled release of encapsulated molecules, coumarin 102, from the nanoparticles under stimulation of UV light, acid and the combined stimuli could be realized. PMID- 26160557 TI - Frequent co-occurrence of high-grade dysplasia in large flat colonic polyps (>20 mm) and synchronous polyps. AB - BACKGROUND: Large colonic polyps are associated with advanced dysplasia, but prevalence and characteristics of synchronous polyps in patients with large flat colonic polyps are poorly investigated. This study aims to characterize clinicopathological features of large flat colonic polyps and their impact on occurrence and characteristics of synchronous polyps. METHODS: A total of 802 patients that underwent endoscopic mucosal resection (EMR) of flat colonic polyps >20 mm from 2003 to 2014 in an academic endoscopy unit were retrospectively analyzed for size, location and histology of large polyps and synchronous polyps. RESULTS: Average size of large polyps was 34.1 mm (range 20-150 mm, standard deviation 16.1 mm). Histology included 52.5 % adenomas with low-grade dysplasia (LGD), 26.7 % with high-grade dysplasia (HGD), 9.6 % serrated polyps and 11.2 % adenocarcinomas. The majority of large polyps were localized in the proximal colon (61 %). 72.2 % of adenocarcinomas were found in the distal colon, while 80.5 % of all serrated polyps were detected in the proximal colon. Increase in polyp size, advanced age and location in the distal colon were associated with presence of HGD/adenocarcinoma in large polyps, as identified by multivariate analysis. Synchronous polyps were detected in 67.2 % of patients undergoing complete colonoscopy during EMR. Presence of HGD/adenocarcinoma in the large polyp, localization of any synchronous polyp in the rectosigmoid colon and occurrence of multiple synchronous polyps were associated with presence of HGD/adenocarcinoma in synchronous polyps. CONCLUSIONS: Synchronous polyps are frequently found in patients with large flat colonic polyps. The prevalence of synchronous polyps with high grade dysplasia is highest in patients with large flat polyps containing HGD/adenocarcinoma. PMID- 26160559 TI - The Biochemical Properties of Antibodies and Their Fragments. AB - Immunoglobulins (Ig) or antibodies are powerful molecular recognition tools that can be used to identify minute quantities of a given target analyte. Their antigen-binding properties define both the sensitivity and selectivity of an immunoassay. Understanding the biochemical properties of this class of protein will provide users with the knowledge necessary to select the appropriate antibody composition to maximize immunoassay results. Here we define the general biochemical properties of antibodies and their similarities and differences, explain how these properties influence their functional relationship to an antigen target, and describe a method for the enzymatic fragmentation of antibodies into smaller functional parts. PMID- 26160560 TI - Hybridoma Technology. AB - The generation of hybridoma cell lines by the fusion of splenocytes from immunized mice with immortal myeloma cells is a well-established method for the production of monoclonal antibodies. Although other methods have emerged as an effective alternative for the generation of monoclonal antibodies, the use of hybridoma technology remains a viable technique that is accessible to a wide number of laboratories that perform basic cell biological research. Hybridoma technology represents a relatively simple procedure at minimal cost for the continuous production of native whole immunoglobulins. This chapter will describe the materials and methodologies needed for the successful generation of monoclonal antibody (mAb)-producing hybridoma cell lines against target antigens. PMID- 26160561 TI - Affinity Purification of Antibodies. AB - Antibodies are provided in a variety of formats that include antiserum, hybridoma culture supernatant, or ascites. They can all be used successfully in crude form for the detection of target antigens by immunoassay. However, it is advantageous to use purified antibody in defined quantity to facilitate assay reproducibility, economy, and reduced interference of nonspecific components as well as improved storage, stability, and bio-conjugation. Although not always necessary, the relative simplicity of antibody purification using commercially available protein A, protein-G, or protein-L resins with basic chromatographic principles warrants purification when antibody source material is available in sufficient quantity. Here, we define three simple methods using immobilized (1) protein-A, (2) protein G, and (3) protein-L agarose beads to yield highly purified antibody. PMID- 26160562 TI - Bioconjugation of Antibodies to Horseradish Peroxidase (HRP). AB - The bioconjugation of an antibody to an enzymatic reporter such as horseradish peroxidase (HRP) affords an effective mechanism by which immunoassay detection of a target antigen can be achieved. The use of heterobifunctional cross-linkers to covalently link antibodies to HRP provides a simple and convenient means to maintain antibody affinity while imparting a functional reporter used for antigen detection. In this chapter, we describe a process by which Sulfo-SMCC is used to generate a stable maleimide-activated HRP that is reactive with sulfhydryl groups generated in antibodies by SATA-mediated thiolation. PMID- 26160563 TI - Indirect ELISA. AB - The enzyme-linked immunosorbent assay (ELISA) is a simple and rapid technique for detecting and quantitating antibodies or antigens attached to a solid surface. Being one of the most sensitive immunoassays, ELISA offers commercial value in laboratory research, diagnostic of disease biomarkers, and quality control in various industries. This technique utilizes an enzyme-linked antibody binding to a surface-attached antigen. Subsequently, a substrate is added to produce either a color change or light signal correlating to the amount of the antigen present in the original sample. This chapter provides the procedures required for carrying out indirect ELISA, one of the many forms of ELISA, to detect polystyrene-immobilized antigen. Methodological approaches to optimize this assay technique are also described, a prerequisite for automation and multiplexing. PMID- 26160564 TI - Direct ELISA. AB - First described by Engvall and Perlmann, the enzyme-linked immunosorbent assay (ELISA) is a rapid and sensitive method for detection and quantitation of an antigen using an enzyme-labeled antibody. Besides routine laboratory usage, ELISA has been utilized in medical field and food industry as diagnostic and quality control tools. Traditionally performed in 96-well or 384-well polystyrene plates, the technology has expanded to other platforms with increase in automation. Depending on the antigen epitope and availability of specific antibody, there are variations in ELISA setup. The four basic formats are direct, indirect, sandwich, and competitive ELISAs. Direct ELISA is the simplest format requiring an antigen and an enzyme-conjugated antibody specific to the antigen. This chapter describes the individual steps for detection of a plate-bound antigen using a horseradish peroxidase (HRP)-conjugated antibody and luminol-based enhanced chemiluminescence (ECL) substrate. The methodological approach to optimize the assay by chessboard titration is also provided. PMID- 26160565 TI - A Double-Sandwich ELISA for Identification of Monoclonal Antibodies Suitable for Sandwich Immunoassays. AB - The sandwich immunoassay (sELISA) is an invaluable technique for concentrating, detecting, and quantifying target antigens. The two critical components required are a capture antibody and a detection antibody, each binding a different epitope on the target antigen. The specific antibodies incorporated into the test define most of the performance parameters of any subsequent immunoassay regardless of the assay format: traditional ELISA, lateral-flow immunoassay, various bead-based assays, antibody-based biosensors, or the reporting label. Here we describe an approach for identifying monoclonal antibodies (mAbs) suitable for use as capture antibodies and detector antibodies in a sELISA targeting bacterial protein toxins. The approach was designed for early identification of monoclonal antibodies (mAbs), in the initial hybridoma screen. PMID- 26160566 TI - ELISpot and DC-ELISpot Assay to Measure Frequency of Antigen-Specific IFNgamma Secreting Cells. AB - ELISpot is a highly sensitive method in immunology to enumerate cells producing a given cytokine. Cells are stimulated in a microtiter plate pre-coated with a specific anti-analyte antibody. In response to the stimulation, cells release cytokines that are bound to the anti-analyte antibody. After a washing step, which removes the cells from the wells, the location of the cytokine-releasing cell is visualized by an enzyme-labeled detection antibody and its corresponding chromogenic substrate. The end result is a set of colored spots, each of which represents an area where a cell secreting the cytokine had been located. Here we describe the standard ELISpot protocol and a variation denominated dendritic cell (DC)-ELISpot for the detection of IFNgamma-secreting cells upon stimulation with oligopeptides and protein antigens, respectively. PMID- 26160567 TI - The Western Blot. AB - Western blotting is a technique that involves the separation of proteins by gel electrophoresis, their blotting or transfer to a membrane, and selective immunodetection of an immobilized antigen. This is an important and routine method for protein analysis that depends on the specificity of antibody-antigen interaction and is useful for the qualitative or semiquantitative identification of specific proteins and their molecular weight from a complex mixture. This chapter will outline the requisite steps including gel electrophoresis of a protein sample, transfer of protein from a gel to a membrane support, and immunodetection of a target antigen. PMID- 26160568 TI - Flow-Through Assay for Detection of Antibodies Using Protein-A Colloidal Gold Conjugate as a Probe. AB - Flow-through assay (FTA) is a rapid, simple-to-perform, cost-effective, and user friendly diagnostic test for monitoring infections in non-laboratory settings. It is mostly applied for antibody detection. FTA employing protein-A colloidal gold conjugate to detect antibodies against porcine cysticerci using cyst fluid and whole cyst antigens of Taenia solium metacestode is described here. Antibodies in the serum are captured by an antigen spotted onto a nitrocellulose membrane mounted on a flow-through device that serves as the antigen capture matrix. The bound antibodies are visualized by the addition of protein-A colloidal gold conjugate, which imparts a pink color. The test can be completed within 3 min at room temperature without any instrumentation. The sensitivity and specificity of the FTA are in agreement with ELISA. PMID- 26160569 TI - Multiplexed Microsphere Suspension Array-Based Immunoassays. AB - ELISA is an extremely powerful tool to detect analytes because of its sensitivity, selectivity, reproducibility and ease of use. Here we describe sandwich immunoassays performed in suspension on spectrally unique microspheres developed by Luminex. Luminex assays offer the benefit of multiplex analysis of large numbers of analytes in a single reaction. Because the microspheres are spectrally unique, many microspheres, each attached to various antibodies, can be added to a single sample. Luminex instruments can distinguish each microsphere and detect the intensity of a reporter signal for each microsphere. Results are reported in Median Fluorescent Intensities for each analyte. Luminex assays can be used to detect up to 500 analytes in a high-throughput format. Luminex refers to this technology as xMAP((r)). Here we describe a routine protocol for a Luminex immunoassay. Other Luminex assays would have to be optimized for specific conditions according to their use. PMID- 26160570 TI - Multiplex Immunoassay: A Planar Array on a Chip Using the MagArray(TM) Technology. AB - Multiplexing is an important tool in assay development as it allows simultaneous detection of numerous analytes. Current platforms with the capability to multiplex are often complex and expensive. Here, we describe a low-cost planar array on a chip capable of simultaneously detecting up to 80 different analytes using the MagArray technology in as little as 10 min. This technology is easy to operate, has a small footprint, and is highly portable as it does not require any moving parts and/or microfluidics. This technology also allows the user to obtain a real-time read-out, which is very useful for analyzing complex sample matrices and for assessing cross-reactivity easily, or to monitor the dissociation of low affinity proteins during washes. The recommended sample volume for analysis is 100 MUL after dilution, but as little as 20 MUL can be measured if needed. PMID- 26160571 TI - Lateral Flow Immunoassay. AB - Lateral flow immunoassays (LFIAs) are a staple in the field of rapid diagnostics. These small handheld devices require no specialized training or equipment to operate, and generate a result within minutes of sample application. They are an ideal format for many types of home test kits, for emergency responders and for food manufacturers and producers looking for a quick evaluation of a given sample. LFIAs rely on high quality monoclonal antibodies that recognize the analyte of interest. As monoclonal antibody technology becomes more accessible to smaller laboratories, there has been increased interest in developing LFIA prototypes for potential commercial manufacture. In this chapter, the basics of designing and building an LFIA prototype are described. PMID- 26160572 TI - Immuno-PCR Assay for Sensitive Detection of Proteins in Real Time. AB - The immuno-PCR (IPCR) assay combines the versatility and robustness of immunoassays with the exponential signal amplification power of the polymerase chain reaction (PCR). Typically, IPCR allows a 10-1,000-fold increase in sensitivity over the analogous enzyme-linked immunosorbent assay (ELISA). This is achieved by replacing the signal-producing antibody-enzyme conjugate of an ELISA with an antibody-DNA conjugate that serves as a marker for PCR amplification. The amplification power of the PCR allows for the detection of even single molecules of nucleic acid templates, making it well suited for a broad range of applications. Here, we describe the application of an IPCR assay for detection of trace amount of antigens using ricin as an example. PMID- 26160573 TI - In Situ Proximity Ligation Assay (PLA). AB - In situ proximity ligation assay (PLA) is a method to identify physical closeness of proteins, where a signal will only be produced if the two proteins are closer than 40 nm, in tissue section or cell cultures. Modifications of the PLA method can also be used to increase specificity or sensitivity of standard immunohistochemistry protocols. PMID- 26160574 TI - Tyramide Signal Amplification for Immunofluorescent Enhancement. AB - Enzyme-linked signal amplification is a key technique used to enhance the immunohistochemical detection of protein, mRNA, and other molecular species. Tyramide signal amplification (TSA) is based on a catalytic reporter deposit in close vicinity to the epitope of interest. The advantages of this technique are its simplicity, enhanced sensitivity, high specificity, and compatibility with modern multi-label fluorescent microscopy. Here, we describe the use of a TSA kit to increase the signal of enhanced green fluorescent protein (eGFP) expressed under the control of Slc17a6 regulatory elements in the brain of a transgenic mouse. The labeling procedure consists of 6 basic steps: (1) tissue preparation, (2) blocking of nonspecific epitopes, (3) binding with primary antibody, (4) binding with horseradish peroxidase-conjugated secondary antibody, (5) reacting with fluorescent tyramide substrate, and (6) imaging of the signal. The procedures described herein detail these steps and provide additional guidance and background to assist novice users. PMID- 26160575 TI - Correlative Microscopy for Localization of Proteins In Situ: Pre-embedding Immuno Electron Microscopy Using FluoroNanogold, Gold Enhancement, and Low-Temperature Resin. AB - Immuno-electron microscopy (immuno-EM) is a technique that has been used widely to determine subcellular localization of proteins. Different approaches are available for immuno-EM: pre-embedding method, post-embedding, and cryosectioning (Tokuyasu "style"). Here we describe a pre-embedding technique that allows the labeling of a target protein in situ, retention of fluorescence signal in plastic, and its localization at the EM level in a given cellular context. The procedure can be technically challenging and labor intensive: it requires optimization of fixation protocols to better preserve the cellular morphology and screening of compatible antibodies. Nevertheless, immuno-EM can be a powerful localization tool. PMID- 26160576 TI - Multiplex ELISA Using Oligonucleotide Tethered Antibodies. AB - Multiplex assays represent a new paradigm for diagnostics. The simultaneous measure of multiple analytes from a single sample is advantageous in creating disease-associated panels that enable more accurate prognosis or diagnosis of the disease state. Furthermore, multiplexing may reduce reagent consumption, sample requirements and labor thereby lowering the cost per test. Here we describe a novel multiplex immunoassay technology based upon creating microarrays in microtiter plates that are formed upon the self-assembly of oligonucleotide antibody conjugates. PMID- 26160577 TI - Gas Plasma Surface Chemistry for Biological Assays. AB - Biological systems respond to and interact with surfaces. Gas plasma provides a scalable surface treatment method for designing interactive surfaces. There are many commercial examples of plasma-modified products. These include well plates, filtration membranes, dispensing tools, and medical devices. This chapter presents an overview of gas plasma technology and provides a guide to using gas plasma for modifying surfaces for research or product development. PMID- 26160578 TI - Explosive or Continuous: Incoherent state determines the route to synchronization. AB - Abrupt and continuous spontaneous emergence of collective synchronization of coupled oscillators have attracted much attention. In this paper, we propose a dynamical ensemble order parameter equation that enables us to grasp the essential low-dimensional dynamical mechanism of synchronization in networks of coupled oscillators. Different solutions of the dynamical ensemble order parameter equation build correspondences with diverse collective states, and different bifurcations reveal various transitions among these collective states. The structural relationship between the incoherent state and the synchronous state leads to different routes of transitions to synchronization, either continuous or discontinuous. The explosive synchronization is determined by the bistable state where the measure of each state and the critical points are obtained analytically by using the dynamical ensemble order parameter equation. Our method and results hold for heterogeneous networks with star graph motifs such as scale-free networks, and hence, provide an effective approach in understanding the routes to synchronization in more general complex networks. PMID- 26160579 TI - A subgroup of MATE transporter genes regulates hypocotyl cell elongation in Arabidopsis. AB - The growth of higher plants is under complex regulation to ensure the elaboration of developmental programmes under a changing environment. To dissect these regulatory circuits, we carried out genetic screens for Arabidopsis abnormal shoot (abs) mutants with altered shoot development. Here, we report the isolation of two dominant mutants, abs3-1D and abs4-1D, through activation tagging. Both mutants showed a 'bushy' loss of apical dominance phenotype. ABS3 and ABS4 code for two closely related putative Multidrug and Toxic Compound Extrusion (MATE) family of efflux transporters, respectively. ABS3 and ABS4, as well as two related MATE genes, ABS3-Like1 (ABS3L1) and ABS3L2, showed diverse tissue expression profiles but their gene products all localized to the late endosome/prevacuole (LE/PVC) compartment. The over-expression of these four genes individually led to the inhibition of hypocotyl cell elongation in the light. On the other hand, the quadruple knockout mutant (mateq) showed the opposite phenotype of an enhanced hypocotyl cell elongation in the light. Hypocotyl cell elongation and de-etiolation processes in the dark were also affected by the mutations of these genes. Exogenously applied sucrose attenuated the inhibition of hypocotyl elongation caused by abs3-1D and abs4-1D in the dark, and enhanced the hypocotyl elongation of mateq under prolonged dark treatment. We determined that ABS3 genetically interacts with the photoreceptor gene PHYTOCHROME B (PHYB). Our results demonstrate that ABS3 and related MATE family transporters are potential negative regulators of hypocotyl cell elongation and support a functional link between the endomembrane system, particularly the LE/PVC, and the regulation of plant cell elongation. PMID- 26160580 TI - Differential responses of grapevine rootstocks to water stress are associated with adjustments in fine root hydraulic physiology and suberization. AB - Water deficits are known to alter fine root structure and function, but little is known about how these responses contribute to differences in drought resistance across grapevine rootstocks. The ways in which water deficit affects root anatomical and physiological characteristics were studied in two grapevine rootstocks considered as low-medium (101-14Mgt) and highly (110R) drought resistant. Rootstocks were grown under prolonged and repeated drying cycles or frequent watering ('dry' and 'wet' treatments, respectively), and the following parameters were evaluated: root osmotic and hydrostatic hydraulic conductivity (Lp os and Lp hyd, respectively), suberization, steady-state root pressure (P rs), sap exudation rates, sap osmotic potential, and exosmotic relaxation curves. For both rootstocks, the 'dry' treatment reduced fine root Lp, elicited earlier root suberization and higher sap osmotic potential, and generated greater P rs after rewatering, but the rootstocks responded differently under these conditions. Lp os, Lp hyd, and sap exudation rates were significantly higher in 110R than in 101-14Mgt, regardless of moisture treatment. Under 'dry' conditions, 110R maintained a similar Lp os and decreased the Lp hyd by 36% compared with 'wet' conditions, while both parameters were decreased by at least 50% for 101 14Mgt under 'dry' conditions. Interestingly, build-up of P rs in 110R was 34% lower on average than in 101-14Mgt, suggesting differences in the development of suberized apoplastic barriers between the rootstocks as visualized by analysis of suberization from fluorescence microscopy. Consistent with this pattern, 110R exhibited the greatest exosmotic Lp os (i.e. Lp os of water flowing from roots to the soil) as determined from relaxation curves under wet conditions, where backflow may have limited its capacity to generate positive xylem pressure. The traits studied here can be used in combination to provide new insights needed for screening drought resistance across grapevine rootstocks. PMID- 26160581 TI - Molecular cloning and characterization of UDP-glucose: furaneol glucosyltransferase gene from grapevine cultivar Muscat Bailey A (Vitis labrusca * V. vinifera). AB - 2,5-Dimethyl-4-hydroxy-3(2H)-furanone (furaneol) is an important aroma compound in fruits, such as pineapple and strawberry, and is reported to contribute to the strawberry-like note in some wines. Several grapevine species are used in winemaking, and furaneol is one of the characteristic aroma compounds in wines made from American grape (Vitis labrusca) and its hybrid grape. Furaneol glucoside was recently isolated as an important furaneol derivative from the hybrid grapevine cultivar, Muscat Bailey A (V. labrusca * V. vinifera), and this was followed by its isolation from some fruits such as strawberry and tomato. Furaneol glucoside is a significant 'aroma precursor of wine' because furaneol is liberated from it during alcoholic fermentation. In this study, a glucosyltransferase gene from Muscat Bailey A (UGT85K14), which is responsible for the glucosylation of furaneol was identified. UGT85K14 was expressed in the representative grape cultivars regardless of species, indicating that furaneol glucoside content is regulated by the biosynthesis of furaneol. On the other hand, furaneol glucoside content in Muscat Bailey A berry during maturation might be controlled by the expression of UGT85K14 along with the biosynthesis of furaneol. Recombinant UGT85K14 expressed in Escherichia coli is able to transfer a glucose moiety from UDP-glucose to the hydroxy group of furaneol, indicating that this gene might be UDP-glucose: furaneol glucosyltransferase in Muscat Bailey A. PMID- 26160582 TI - Two homologous protein S-acyltransferases, PAT13 and PAT14, cooperatively regulate leaf senescence in Arabidopsis. AB - Lipid modification on the cysteine residues of proteins, known as S palmitoylation or S-acylation, regulates the subcellular localization and the function of proteins. S-acylation is catalysed by a group of protein acyltransferases (PATs) with a conserved Asp-His-His-Cys (DHHC) motif. The molecular function of S-acylation has been studied in details in yeast and mammalian cells, but its role in plant cells remains unclear. Here it is reported that the expression of two homologous protein acyltransferases- PAT13 and PAT14 was moderately increased in the older leaves of Arabidopsis. The double mutant of PAT13 and PAT14 displayed a severely early leaf senescence phenotype. The phenotype was complemented by PAT13 or PAT14 overexpression in the double mutant, confirming the roles of PAT13 and PAT14 in this process. Furthermore, the levels of reactive oxygen species (ROS) and cell death were dramatically induced in the double mutant. To investigate the molecular functions of PAT13 and PAT14, their potential S-acylation substrates were predicted by bioinformatics methods. The subcellular localization and S-acylation of a candidate substrate NITRIC OXIDE ASSOCIATED 1 (NOA1), which also plays a role in leaf senescence control, were partially disrupted in the protoplasts of the double mutant. Impairment of S acylation on NOA1 affected its subcellular localization and its function in leaf senescence regulation. Conclusively, protein S-acyltransferases PAT13 and PAT14 are involved in leaf senescence control- possibly via NOA1 S-acylation-, providing a new sight into the regulation mechanism of S-acylation in leaf senescence. PMID- 26160583 TI - A Kunitz-type protease inhibitor regulates programmed cell death during flower development in Arabidopsis thaliana. AB - Flower development and fertilization are tightly controlled in Arabidopsis thaliana. In order to permit the fertilization of a maximum amount of ovules as well as proper embryo and seed development, a subtle balance between pollen tube growth inside the transmitting tract and pollen tube exit from the septum is needed. Both processes depend on a type of programmed cell death that is still poorly understood. Here, it is shown that a Kunitz protease inhibitor related to water-soluble chlorophyll proteins of Brassicaceae (AtWSCP, encoded by At1g72290) is involved in controlling cell death during flower development in A. thaliana. Genetic, biochemical, and cell biology approaches revealed that WSCP physically interacts with RD21 (RESPONSIVE TO DESICCATION) and that this interaction in turn inhibits the activity of RD21 as a pro-death protein. The regulatory circuit identified depends on the restricted expression of WSCP in the transmitting tract and the septum epidermis. In a respective Atwscp knock-out mutant, flowers exhibited precocious cell death in the transmitting tract and unnatural death of septum epidermis cells. As a consequence, apical-basal pollen tube growth, fertilization of ovules, as well as embryo development and seed formation were perturbed. Together, the data identify a unique mechanism of cell death regulation that fine-tunes pollen tube growth. PMID- 26160584 TI - Regulation of plant growth and development by the GROWTH-REGULATING FACTOR and GRF-INTERACTING FACTOR duo. AB - Transcription factors are key regulators of gene expression and play pivotal roles in all aspects of living organisms. Therefore, identification and functional characterization of transcription factors is a prerequisite step toward understanding life. This article reviews molecular and biological functions of the two transcription regulator families, GROWTH-REGULATING FACTOR (GRF) and GRF-INTERACTING FACTOR (GIF), which have only recently been recognized. A myriad of experimental evidence clearly illustrates that GRF and GIF are bona fide partner proteins and form a plant-specific transcriptional complex. One of the most conspicuous outcomes from this research field is that the GRF-GIF duo endows the primordial cells of vegetative and reproductive organs with a meristematic specification state, guaranteeing the supply of cells for organogenesis and successful reproduction. It has recently been shown that GIF1 proteins, also known as ANGUSTIFOLIA3, recruit chromatin remodelling complexes to target genes, and that AtGRF expression is directly activated by the floral identity factors, APETALA1 and SEPALLATA3, providing an important insight into understanding of the action of GRF-GIF. Moreover, GRF genes are extensively subjected to post-transcriptional control by microRNA396, revealing the presence of a complex regulatory circuit in regulation of plant growth and development by the GRF-GIF duo. PMID- 26160585 TI - Erratum to: First-in-human evaluation of a hybrid modality that allows combined radio- and (near-infrared) fluorescence tracing during surgery. PMID- 26160587 TI - In vivo impact of intra-aortic balloon counterpulsation on reducing ischemia and improving myocardial blood flow: Proof from a PET rubidium-82 study. PMID- 26160588 TI - Autonomic innervation of the heart: Role of molecular imaging. PMID- 26160589 TI - FDG PET/CT in the staging and follow-up of primary cardiac 'T' cell lymphoma presenting as hypertrophic cardiomyopathy. PMID- 26160590 TI - Beta-adrenergic antagonists during general anesthesia reduced postoperative pain: a systematic review and a meta-analysis of randomized controlled trials. AB - We have performed a systematic literature review and a meta-analysis investigating the effect of beta-adrenergic antagonist on perioperative pain in randomized clinical trials (RCTs). The search included the CENTRAL, CINAHL, EMBASE, and MEDLINE databases (from inception to 10 February 2015). From the retrieved full texts, we hand-searched the references and PubMed related citations. A total of 11 RCTs consisting data of 701 adult patients were eligible for this systematic review. Esmolol was evaluated in ten trials and propranolol in one. Esmolol decreased the need for rescue analgesics by 32-50%; p < 0.05 (n = 7) and the proportion of patients needing rescue analgesia from 100 to 65%; p < 0.005 (n = 1), and propranolol decreased the need for rescue analgesics by 72%; p < 0.001 (n = 1). The time to the first rescue analgesics was longer (p < 0.05) and pain ratings were lower (p < 0.05) in patients with beta-adrenergic antagonists. However, in two opioid-controlled studies, one in knee arthroscopy and another in tubal ligation patients, the proportion of patients needing rescue analgesia was two-times higher in esmolol-treated patients: 52-57 vs. 23-34%, p < 0.05. Adverse effects were rarely reported, and as reported were mostly cardiovascular alterations. In conclusion, intra-operative beta-adrenergic antagonists' administration may decrease postoperative pain and analgesic consumption when given as an adjuvant to general anesthesia. PMID- 26160592 TI - Simultaneous and selective isolation of multiple subpopulations of rare cells from peripheral blood using ensemble-decision aliquot ranking (eDAR). AB - Rare cells, such as circulating tumor cells (CTCs), can be heterogeneous. The isolation and identification of rare cells with different phenotypes is desirable, for clinical and biological applications. However, CTCs exist in a complex biological environment, which complicates the isolation and identification of particular subtypes. To address this need, we re-designed our ensemble-decision aliquot ranking (eDAR) system to detect, isolate, and study two subpopulations of rare cells in the same microchip. With this dual-capture eDAR device, we simultaneously and selectively isolated two subsets of CTCs from the same blood sample: One set expressed epithelial markers and the other had mesenchymal characteristics. We could apply other selection schemes with different sorting logics to isolate the two subpopulations on demand. The average recovery rate for each subpopulation was higher than 88% with a nearly 100% selectivity of the targeted cells; the throughput was 50 MUL min(-1). PMID- 26160591 TI - Factors affecting survival in pediatric cardiac tamponade caused by central venous catheters. AB - Pediatric central venous catheter (CVC) placement is useful but associated with complications such as cardiac tamponade. We aimed to identify risk factors for death in cardiac tamponade. Published articles on pediatric CVC-associated cardiac tamponade were obtained by searching PubMed and Google and retrospectively reviewed to analyze risk factors for death. Factors examined for their effect on mortality risk included patient age, weight, CVC size, days from CVC insertion to tamponade occurrence, substances administered, insertion site, treatment, CVC material, and initial CVC tip position. Of 110 patients reported in 62 articles, 69 survived and 41 died. Among survivors, 55 of 69 patients were treated; among deaths, only 7 of 38 (OR 537.9, 95% CI 29.3-9,877, p < 0.0001). Multiple regression analysis in 44 cases showed that treatment (p < 0.0001) and initial CVC tip position (p = 0.020) were independent predictive factors related to improved cardiac tamponade survival. Past studies have mainly discussed how to avoid pediatric cardiac tamponade; by contrast, the present study focused on how to avoid deaths. The findings of this review suggest that cardiac tamponade survival is better when tamponade is detected early and treated promptly and might be affected by initial CVC tip position. PMID- 26160594 TI - Schwannoma and Leiomyoma of the Colon in a Patient with Ulcerative Colitis. PMID- 26160593 TI - Spexin Enhances Bowel Movement through Activating L-type Voltage-dependent Calcium Channel via Galanin Receptor 2 in Mice. AB - A novel neuropeptide spexin was found to be broadly expressed in various endocrine and nervous tissues while little is known about its functions. This study investigated the role of spexin in bowel movement and the underlying mechanisms. In functional constipation (FC) patients, serum spexin levels were significantly decreased. Consistently, in starved mice, the mRNA of spexin was significantly decreased in intestine and colon. Spexin injection increased the velocity of carbon powder propulsion in small intestine and decreased the glass beads expulsion time in distal colon in mice. Further, spexin dose-dependently stimulated the intestinal/colonic smooth muscle contraction. Galanin receptor 2 (GALR2) antagonist M871, but not Galanin receptor 3 (GALR3) antagonist SNAP37899, effectively suppressed the stimulatory effects of spexin on intestinal/colonic smooth muscle contraction, which could be eliminated by extracellular [Ca(2+)] removal and L-type voltage-dependent Ca(2+) channel (VDCC) inhibitor nifedipine. Besides, spexin dramatically increased the [Ca(2+)]i in isolated colonic smooth muscle cells. These data indicate that spexin can act on GALR2 receptor to regulate bowel motility by activating L-type VDCC. Our findings provide evidence for important physiological roles of spexin in GI functions. Selective action on spexin pathway might have therapeutic effects on GI diseases with motility disorders. PMID- 26160595 TI - Marginal Iodine Status and High Rate of Subclinical Hypothyroidism in Washington DC Women Planning Conception. AB - INTRODUCTION: Subclinical hypothyroidism during pregnancy has been associated with adverse maternal and fetal outcomes. A subset of pregnant women in the United States have been shown to have mild iodine deficiency. No study has evaluated the thyroid and iodine status of women who are planning to become pregnant in the near future. METHODS: Thyroid function tests, thyroid antibodies, and urine iodine levels were evaluated in women presenting for preconception screening and counseling. A thyrotropin (TSH) level above 3.0 mIU/L was considered abnormal. RESULTS: One hundred and forty one women enrolled in the study. The median TSH level was 1.70 mIU/L (range 0.43-5.3 mIU/L). Sixteen women (11%) had a TSH above the upper limit of normal (>3.0 mIU/L). Eleven women (8%) were positive for TPO-Ab and 21 women (15%) for TgAb. Twenty-three women (16%) were positive for at least one thyroid antibody (TPOAb and/or TgAb). Median serum TSH concentrations were higher in women with detectable antithyroid antibodies than in women who were antibody negative (2.2 mIU/L vs. 1.7 mIU/L; p=0.005). The median urinary iodine concentration was 100.5 MUg (range 19-843 MUg/L). DISCUSSION: The present cohort exhibited the lowest median urinary iodine concentration levels to date reported in the United States for women in their childbearing years. One out of every nine women (11%) had thyroid function tests consistent with subclinical hypothyroidism. PMID- 26160596 TI - Raspberry ketone in food supplements--High intake, few toxicity data--A cause for safety concern? AB - Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is marketed on the Internet as a food supplement. The recommended intake is between 100 and 1400 mg per day. The substance is naturally occurring in raspberries (up to 4.3 mg/kg) and is used as a flavouring substance. Toxicological studies on raspberry ketone are limited to acute and subchronic studies in rats. When the lowest recommended daily dose of raspberry ketone (100 mg) as a food supplement is consumed, it is 56 times the established threshold of toxicological concern (TTC) of 1800 MUg/day for Class 1 substances. The margin of safety (MOS) based on a NOAEL of 280 mg/kg bw/day for lower weight gain in rats is 165 at 100 mg and 12 at 1400 mg. The recommended doses are a concern taking into account the TTC and MOS. Investigations of raspberry ketone in quantitative structure-activity relationship (QSAR) models indicated potential cardiotoxic effects and potential effects on reproduction/development. Taking into account the high intake via supplements, the compound's toxic potential should be clarified with further experimental studies. In UK the pure compound is regarded as novel food requiring authorisation prior to marketing but raspberry ketone is not withdrawn from Internet sites from this country. PMID- 26160597 TI - How reliable are crystalline silica dust concentration measurements? AB - To determine how reliably commercial laboratories measure crystalline silica concentrations corresponding to OSHA's proposed limits, 105 filters were prepared with known masses of 20, 40, and 80 MUg of respirable quartz corresponding to airborne silica concentrations of 25, 50, and 100 MUg/m(3) and were submitted, in a blind test, to qualified commercial laboratories over a nine month period. Under these test conditions, the reported results indicated a lack of accuracy and precision needed to reliably inform regulatory compliance decisions. This was true even for filters containing only silica, without an interfering matrix. For 36 filters loaded with 20 or more micrograms of silica, the laboratories reported non-detected levels of silica. Inter-laboratory variability in this performance test program was so high that the reported results could not be used to reliably discriminate among filters prepared to reflect 8-h exposures to respirable quartz concentrations of 25, 50 and 100 MUg/m(3). Moreover, even in intra-laboratory performance, there was so much variability in the reported results that 2-fold variations in exposure concentrations could not be reliably distinguished. Part of the variability and underreporting may result from the sample preparation process. The results of this study suggest that current laboratory methods and practices cannot necessarily be depended on, with high confidence, to support proposed regulatory standards with reliable data. PMID- 26160598 TI - Vulvar metastasis from carcinoma breast unveiling distant metastasis: Exploring an unusual metastatic pattern. AB - A 76 year old woman with a previous history of infiltrating ductal carcinoma of right breast (diagnosed and treated 14 years back) presented to us with a non healing ulcer on the left side of the vulva along with two satellite nodules close to the vulvar lesion. Biopsy showed an infiltrating ductal carcinoma of breast with a strong positivity for estrogen/progesterone receptors. Further, (18)F-FDG PET-CT (Fluoro-deoxy glucose positron emission tomography computed tomography) showed multiple bilateral lung metastases. She responded well to hormone therapy (Letrozole) with decrease in the size of primary vulvar lesion and disappearance of the satellite nodules. Repeating PET-CT at 6 months showed partial response of the lung lesions. The present case is unique in the way of metastatic presentation of breast cancer to vulva after a long gap of primary diagnosis (longest reported till date) and also in unveiling of further metastatic sites in otherwise asymptomatic case. Patients (particularly elderly) with this unusual and clinically isolated pattern of metastasis might remain misdiagnosed for a long period of time and this case report aims to increase the awareness of clinicians toward the same. Gynecological surveillance remains of paramount importance in the follow up of breast cancer. PMID- 26160599 TI - Delayed mirror visual feedback presented using a novel mirror therapy system enhances cortical activation in healthy adults. AB - BACKGROUND: Mirror visual feedback (MVF) generated in mirror therapy (MT) with a physical mirror promotes the recovery of hemiparetic limbs in patients with stroke, but is limited in that it cannot provide an asymmetric mode for bimanual coordination training. Here, we developed a novel MT system that can manipulate the MVF to resolve this issue. The aims of this pilot study were to examine the feasibility of delayed MVF on MT and to establish its effects on cortical activation in order to understand how it can be used for clinical applications in the future. METHODS: Three conditions (no MVF, MVF, and 2-s delayed MVF) presented via our digital MT system were evaluated for their time-course effects on cortical activity by event-related desynchronization (ERD) of mu rhythm electroencephalography (EEG) during button presses in 18 healthy adults. Phasic ERD areas, defined as the areas of the relative ERD curve that were below the reference level and within -2-0 s (P0), 0-2 s (P1), and 2-4 s (P2) of the button press, were used. RESULTS: The overall (P0 to P2) and phasic ERD areas were higher when MVF was provided compared to when MVF was not provided for all EEG channels (C3, Cz, and C4). Phasic ERD areas in the P2 phase only increased during the delayed-MVF condition. Significant enhancement of cortical activation in the mirror neuron system and an increase in attention to the unseen limb may play major roles in the response to MVF during MT. In comparison to the no MVF condition, the higher phasic ERD areas that were observed during the P1 phase in the delayed-MVF condition indicate that the image of the still hand may have enhanced the cortical activation that occurred in response to the button press. CONCLUSIONS: This study is the first to achieve delayed MVF for upper-limb MT. Our approach confirms previous findings regarding the effects of MVF on cortical activation and contributes additional evidence supporting the use of this method in the future for upper-limb motor training in patients with stroke. PMID- 26160600 TI - Auspicious birth dates among Chinese in California. AB - The number eight is considered lucky in Chinese culture, e.g. the Beijing Olympics began at 8:08 pm on 8/8/2008. Given the potential for discretion in selecting particular dates of labor induction or scheduled Cesarean section (C section), we consider whether Chinese-American births in California occur disproportionately on the 8th, 18th, or 28th day of the month. We find 2.3% "too many" Chinese births on these auspicious birth dates, whereas Whites show no corresponding increase. The increase in Chinese births is driven by higher parity C-sections: the number of repeat C-sections is 6% "too high" on auspicious birth dates. Sons born to Chinese parents account for the entire increase; daughter deliveries do not seem to be timed to achieve "lucky" birth dates. We also find avoidance of repeat C-section deliveries on the 4th, 14th, and 24th of the month, considered unlucky in Chinese culture. Finally, we replicate earlier work finding that Friday the 13th delivery dates are avoided and document a particularly large decrease among Chinese. For Whites and Chinese in California, mothers with higher levels of education are particularly likely to avoid delivering on the 13th. PMID- 26160601 TI - Respect for Human Vulnerability: The Emergence of a New Principle in Bioethics. AB - Vulnerability has become a popular though controversial topic in bioethics, notably since 2000. As a result, a common body of knowledge has emerged (1) distinguishing between different types of vulnerability, (2) criticizing the categorization of populations as vulnerable, and (3) questioning the practical implications. It is argued that two perspectives on vulnerability, i.e., the philosophical and political, pose challenges to contemporary bioethics discourse: they re-examine the significance of human agency, the primacy of the individual person, and the negativity of vulnerability. As a phenomenon of globalization, vulnerability can only be properly addressed in a global bioethics that takes the social dimension of human existence seriously. PMID- 26160602 TI - Parental Virtue and Prenatal Genetic Alteration Research. AB - Although the philosophical literature on the ethics of human prenatal genetic alteration (PGA) purports to inform us about how to act, it rarely explicitly recognizes the perspective of those who will be making the PGA decision in practice. Here I approach the ethics of PGA from a distinctly virtue-based perspective, taking seriously what it means to be a good parent making this decision for one's child. From this perspective, I generate a sound verdict on the moral standing of human PGA (research): given the current state of the art, good parents have compelling reason not to consent to PGA (research) for their child, especially as part of the first wave(s) of PGA research participants and especially for non-medically oriented purposes. This is because doing otherwise is inconsistent with a plausible and defensible understanding of virtuous parenting and parental virtues, founded on a genuine concern for promoting the overall flourishing of the eventual child. In essence, given the current and foreseeable state of the art, parents who allow prenatal genetic alteration of their children are less-than-virtuous parents to those children, even in cases where they have a right to do so and even if PGA turns out to be beneficial to the eventual child. PMID- 26160603 TI - Decision-Making: At the End of Life and the Provision of Pretreatment Advice. PMID- 26160604 TI - AIDS Panic in the Twenty-First Century: The Tenuous Legal Status of HIV-Positive Persons in America. AB - Thirty-four states criminalize HIV in some way, whether by mandating disclosure of one's HIV status to all sexual partners or by deeming the saliva of HIV positive persons a "deadly weapon." In this paper, we argue that HIV-specific criminal laws are rooted in historical prejudice against HIV-positive persons as a class. While purporting to promote public health goals, these laws instead legally sanction discrimination against a class of persons. PMID- 26160605 TI - Syntheses, crystal structures, weak interaction, magnetic and photoluminescent properties of two new organic-inorganic molecular solids with disubstituted benzyl triphenylphosphinium and tetra(isothiocyanate)cobalt(II) anion. AB - Two new organic-inorganic molecular solids of tetra(isothiocyanate)cobalt(II) dianion and disubstituted benzyl triphenylphosphinium, [2Cl4FBzTPP]2[Co(NCS)4] (1) and [2Cl4ClBzTPP]2[Co(NCS)4] (2) ([2Cl4FBzTPP](+)=1-(2'-chloro-4' fluorobenzyltriphenylphosphonium) and [2Cl4ClBzTPP](+)=1-(2',4' dichlorobenzyltriphenylphosphonium), were synthesized and characterized by elemental analysis, FT-IR, UV-Vis spectra, ESI-MS and single crystal X-ray diffraction method. Compounds 1 and 2 crystallize in the monoclinic Pc and triclinic P-1, respectively. The Co(II) ion of the [Co(NCS)4](2-) anion shows a distorted tetrahedral coordination geometry. The [2Cl4FBzTPP](+) cations containing P(2) atoms in 1 form a column by the Cl?pi interactions, while the [2Cl4ClBzTPP](+) cations in 2 form two columns by the C-H?pi and pi?pi interactions. The anion and the cation are linked by C-H?S hydrogen bonds and Cl?S interactions. Magnetic susceptibility measurement in the temperature range 2 300K shows that both 1 and 2 exhibit a weak antiferromagnetic exchange interaction as the temperature falls, and ultraviolet fluorescence emission in the solid state at room temperature. PMID- 26160606 TI - Understanding next generation sequencing in oncology: A guide for oncologists. AB - DNA sequencing is now faster and cheaper than ever before, due to the development of next generation sequencing (NGS) technologies. NGS is now widely used in the research setting and is becoming increasingly utilised in clinical practice. However, due to evolving clinical commitments, increased workload and lack of training opportunities, many oncologists may be unfamiliar with the terminology and technology involved. This can lead to oncologists feeling daunted by issues such as how to interpret the vast amounts of data generated by NGS and the differences between sequencing platforms. This review article explains common concepts and terminology, summarises the process of DNA sequencing (including data analysis) and discusses the main factors to consider when deciding on a sequencing method. This article aims to improve oncologists' understanding of the most commonly used sequencing platforms and the ongoing challenges faced in expanding the use of NGS into routine clinical practice. PMID- 26160607 TI - Risk of grade 3-4 diarrhea and mucositis in colorectal cancer patients receiving anti-EGFR monoclonal antibodies regimens: A meta-analysis of 18 randomized controlled clinical trials. AB - The anti-Epidermal Growth Factor Receptor monoclonal antibodies (anti-EGFR MoAbs) are beneficial in the treatment of wild type (WT) KRAS colorectal cancer, but are burdened by serious toxicities. We conducted a systematic review and meta analysis to determine incidence and relative risk (RR) of severe and life threatening diarrhoea and mucositis in colorectal cancer patients and WT-KRAS subpopulation. PubMed and Embase were searched for trials comparing the same therapeutic regimens with or without anti-EGFR for colorectal cancer. Data on severe and life-threatening diarrhoea and mucositis were extracted from 18 studies involving 13,382 patients. Statistical analyses calculated incidence of AEs, RRs and 95% confidence intervals by using either random or fixed effects models. Patients receiving anti-EGFR MoAbs showed an increased risk of diarrhoea (RR: 1.66, CI 1.52-1.80) and mucositis (RR: 3.44, CI 2.66-4.44). The risk was similar among WT-KRAS patients. Prevention and risk reduction strategies of these AEs are mandatory to optimize clinical outcomes. PMID- 26160608 TI - A crossover study comparing gabapentin and fluoxetine for the treatment of vasomotor symptoms among postmenopausal women. AB - OBJECTIVE: To compare the effectiveness of fluoxetine and gabapentin for treatment of vasomotor symptoms (VMS) after the menopause. METHODS: Between March 2011 and March 2012, a randomized crossover study was performed at a center in Semnan, Iran, among postmenopausal women aged 45-57 years with hot flashes (>=2 per day for previous 4 months) for which they had received no previous treatment. Participants were divided into two groups with consecutive numbers assigned in order of recruitment. In the first treatment round (4 weeks), group A received 20mg/day fluoxetine and group B received 300 mg/day gabapentin. After a 2-week washout period, group A received gabapentin and group B received fluoxetine in a second round (4 weeks). Information about VMS was obtained with the Greene Climacteric Scale questionnaire. Participants and all investigators except one were masked to group assignment. RESULTS: Data for 79 participants (39 in group A, 40 in group B) were analyzed. In both treatment rounds, gabapentin caused greater reductions in the severity of hot flashes than did fluoxetine (P<0.001 for both). After the first round of treatment, those who had received gabapentin reported greater reductions in the severity of night sweats (P<0.001). CONCLUSION: Gabapentin at a dose of 300 mg/day is more effective for treatment of VMS among postmenopausal women than is 20 mg/day fluoxetine. Iranian Registry of Clinical Trials:IRCT2014092711019N3. PMID- 26160610 TI - MiR-323 Inhibits Prostate Cancer Vascularization Through Adiponectin Receptor. AB - BACKGROUND/AIMS: The current treatments fail to provide satisfactory cure for aggressive prostate cancers (PCs). Hence, further comprehension of PC metastasis is highly appreciated for improving the levels of therapy. We have previously shown that Adiponectin reduces the levels of vascular endothelial growth factor A (VEGF-A) in PCs to suppress tumor-associated neovascularization, possibly through AMPK/mTor signaling. Here, we studied the regulation of Adiponectin signaling in PCs. METHODS: We analyzed the levels and correlation of Adiponectin receptor 1 (AdipoR1) and microRNA-323 (miR-323) in the PC specimen, compared to the paired normal prostate tissue. We analyzed the binding of miR-323 to the 3'UTR of AdipoR1 mRNA and its effects on AdipoR1 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-323 levels in PC cells, and examined the effects on the expression of AdipoR1 and VEGF-A, as well as on vessel formation in a human umbilical vein endothelial cells (HUVECs) transwell collagen gel assay. RESULTS: We detected significantly lower levels of AdipoR1 and significantly higher levels of miR-323 in PC specimen. Moreover, the levels of AdipoR1 and miR-323 are inversely correlated. Moreover, miR-323 was found to bind to the 3'UTR of AdipoR1 mRNA to inhibit its translation. Overexpression of miR-323 in PC cells decreased AdipoR1 protein levels, whereas inhibition of miR-323 increased AdipoR1 protein levels, without affecting AdipoR1 transcripts. Moreover, overexpression of miR-323 increased the levels of VEGF-A and the vessel formation by HUVECs, while inhibition of miR- 323 decreased the levels of VEGF-A and the vessel formation by HUVECs. CONCLUSION: Our data demonstrate that miR-323 may increase VEGF-A-mediated cancer vascularization in PC cells through AdipoR1 suppression. PMID- 26160609 TI - Differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of pain in human rotator cuff tendinopathy. AB - INTRODUCTION: The relationship between peripheral tissue characteristics and pain symptoms in soft tissue inflammation is poorly understood. The primary aim of this study was to determine immunohistochemical differences in tissue obtained from patients with persistent pain and patients who had become pain-free after surgical treatment for rotator cuff tendinopathy. The secondary aim was to investigate whether there would be differences in glutaminergic and inflammatory gene expression between disease-derived and healthy control cells in vitro. METHODS: Supraspinatus tendon biopsies were obtained from nine patients with tendon pain before shoulder surgery and from nine further patients whose pain had resolved completely following shoulder surgery. Histological markers relating to the basic tendon characteristics, inflammation and glutaminergic signalling were quantified by immunohistochemical analysis. Gene expression of glutaminergic and inflammatory markers was determined in tenocyte explants derived from painful rotator cuff tendon tears in a separate cohort of patients and compared to that of explants from healthy control tendons. Dual labelling was performed to identify cell types expressing nociceptive neuromodulators. RESULTS: Tendon samples from patients with persistent pain demonstrated increased levels of metabotropic glutamate receptor 2 (mGluR2), kainate receptor 1 (KA1), protein gene product 9.5 (PGP9.5), CD206 (macrophage marker) and CD45 (pan-leucocyte marker) versus pain-free controls (p <0.05). NMDAR1 co-localised with CD206 positive cells, whereas PGP9.5 and glutamate were predominantly expressed by resident tendon cells. These results were validated by in vitro increases in the expression of mGluR2, N-methyl-D-aspartate receptor (NMDAR1), KA1, CD45, CD206 and tumour necrosis factor alpha (TNF-alpha) genes (p <0.05) in disease-derived versus control cells. CONCLUSIONS: We conclude that differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of shoulder pain in rotator cuff tendinopathy, and that disease-derived cells exhibit a distinctly different neuro-inflammatory gene expression profile to healthy control cells. PMID- 26160611 TI - Polymorphisms in PLA2G6 and PLA2G4C genes for calcium-independent phospholipase A2 do not contribute to attenuated niacin skin flush response in schizophrenia patients. AB - We hypothesized that attenuated niacin skin flushing in schizophrenia patients might be associated with polymorphic variants in PLA2G6 and PLA2G4C genes (rs4375 and rs1549637 variations) which encode calcium-independent phospholipase A2 beta (iPLA2beta) and cytosolic phospholipase A2 gamma (cPLA2gamma) enzymes. The iPLA2beta and cPLA2gamma may play an important role in niacin-mediated signaling; in addition to their major role - mediating phospholipids remodeling, which alters membrane receptors and signal transduction, they regulate the reservoir of arachidonic acid for prostaglandins synthesis. Skin response to topical niacin of 0.1M, 0.01M, 0.001M and 0.0001M concentrations in 75 schizophrenia patients was rated using the method of volumetric niacin response (VNR). Neither PLA2G6 nor PLA2G4C gene polymorphisms were significantly associated with VNR values. Furthermore, polymorphisms' synergy on niacin skin flushing was also not detected. PMID- 26160612 TI - Iron homeostasis in host defence and inflammation. AB - Iron is an essential trace element for multicellular organisms and nearly all microorganisms. Although iron is abundant in the environment, common forms of iron are minimally soluble and therefore poorly accessible to biological organisms. Microorganisms entering a mammalian host face multiple mechanisms that further restrict their ability to obtain iron and thereby limit their pathogenicity. Iron levels also modulate host defence, as iron content in macrophages regulates their cytokine production. Here, we review recent advances that highlight the role of systemic and cellular iron-regulating mechanisms in protecting hosts from infection, emphasizing aspects that are applicable to human health and disease. PMID- 26160614 TI - T cell differentiation: NLRP3 goes beyond the inflammasome. PMID- 26160615 TI - Autoimmunity: Benefits of exhaustion. PMID- 26160616 TI - Introduction to a Special Issue Dialectical Behavior Therapy: Evolution and Adaptations in the 21(st) Century. AB - Born from the randomized controlled trial by Linehan and colleagues in 1991, dialectical behavior therapy (DBT) has become the gold standard for treatment of individuals who are suicidal and have borderline personality disorder. In this special issue, we begin with a historical review of DBT provided by the treatment developer herself. We then introduce readers to new, 21(st) century adaptations developed of this treatment modality. In this issue we explore the use of DBT for suicidal adolescents with one paper focusing on Latina teens and their parents, and one focused on the more recently developed walking the middle path skills module. Other papers in this issue include unique adaptations of DBT for eating disorders, and disorders of over-control, as well as trauma in incarcerated male adolescents. We also look at transdiagnostic applications of DBT and finally a comparison of DBT with mentalization-based treatment. PMID- 26160617 TI - The Course and Evolution of Dialectical Behavior Therapy. AB - Dialectical behavior therapy was originally developed from early efforts to apply standard behavior therapy to treat individuals who were highly suicidal. Its development was a trial and error effort driven primarily from clinical experience. Dialectical behavior therapy is a modular and hierarchical treatment consisting of a combination of individual psychotherapy, group skills, training, telephone coaching, and a therapist consultation team. The inherent modularity and hierarchical structure of DBT has allowed for relative ease in adapting and applying the treatment to other populations and settings. New skills have been developed and/or modified due to clinical need and/or advancement in research such as treatment outcomes or mechanisms. There has been an effort to implement DBT skills as a standalone treatment. More research is needed to assess how DBT skills work and for whom. As DBT broadens its reach, the treatment will continue to grow and adapt to meet demands of an evolving clinical landscape. PMID- 26160619 TI - Dialectical Behavior Therapy and Eating Disorders: The Use of Contingency Management Procedures to Manage Dialectical Dilemmas. AB - Several researchers have adapted and/or applied dialectical behavior therapy (DBT) for populations with eating disorders. There is a growing body of research that indicates that DBT is an effective treatment option for this population, including those who have co-occurring Axis II disorders. The goal of the current paper is to summarize the research conducted in the area of DBT with those individuals who present with eating disorders only as well as those who present with both eating disorders and Axis II disorders. We also describe a dialectical dilemma, apparent compliance vs. active defiance, which is commonly observed in the group with comorbidities A DBT change strategy, contingency management, is discussed as an intervention to target apparent compliance and active defiance. PMID- 26160618 TI - Transdiagnostic Applications of DBT for Adolescents and Adults. AB - Dialectical behavior therapy (DBT) is an empirically supported treatment that was originally developed for chronically suicidal adults. Since the publication of the original treatment manual, DBT has been reconceptualized as a treatment that is broadly applicable for individuals who have difficulties regulating emotion. As such, the treatment can be applied transdiagnostically. Based on the flexibility and adaptability of the treatment, several adaptations have been made to the original protocol. Considerable empirical evidence now supports the use of DBT adapted for eating disorders, substance use disorders, and posttraumatic stress disorder. Moreover, developmentally appropriate adaptations have made the treatment applicable to youth samples. The current paper is geared toward practitioners and describes the various ways in which DBT has been modified for use with various populations and age ranges. PMID- 26160620 TI - Radically Open-Dialectical Behavior Therapy for Disorders of Over-Control: Signaling Matters. AB - Radically Open-Dialectical Behavior Therapy (RO-DBT) is a transdiagnostic treatment designed to address a spectrum of difficult-to-treat disorders sharing similar phenotypic and genotypic features associated with maladaptive over control-such as anorexia nervosa, chronic depression, and obsessive compulsive personality disorder. Over-control has been linked to social isolation, aloof and distant relationships, cognitive rigidity, high detailedfocused processing, risk aversion, strong needs for structure, inhibited emotional expression, and hyper perfectionism. While resting on the dialectical underpinnings of standard DBT, the therapeutic strategies, core skills, and theoretical perspectives in RO-DBT often substantially differ. For example, RO-DBT contends that emotional loneliness secondary to low openness and social-signaling deficits represents the core problem of over-control, not emotion dysregulation. RO-DBT also significantly differs from other treatment approaches, most notably by linking the communicative functions of emotional expression to the formation of close social bonds and via skills targeting social-signaling and changing neurophysiological arousal. The aim of this paper is to provide a brief overview of the core theoretical principles and unique treatment strategies underlying RO DBT. PMID- 26160621 TI - Treatment Acceptability Study of Walking The Middle Path, a New DBT Skills Module for Adolescents and their Families. AB - In light of dialectic behavioral therapy's effectiveness in treating suicidal adults, the treatment has been adapted for use in diverse clinical populations, including adolescents who are suicidal and have multiple problem. Walking the Middle Path is a new skill- training module that addresses specific problems and skill deficits of adolescents and their families. The present study evaluated the acceptability of Walking the Middle Path, in order to establish a basis for further assessment of the module's effectiveness. Fifty participants receiving DBT for adolescent were administered a Treatment Acceptability Scale, a skills rating scale and an open-ended, qualitative assessment. Results indicated high ratings of acceptability. Middle Path skills ranked highly among the DBT skills perceived as most helpful, with validation rated the most beneficial aspect of skills training. The study provides preliminary support for inclusion of Middle Path in the skills training component of DBT with adolescents and their caregivers. Clinical implications of responses and the role of validation in improving family functioning are discussed. PMID- 26160613 TI - The multifaceted biology of plasmacytoid dendritic cells. AB - Plasmacytoid dendritic cells (pDCs) are a unique DC subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases that are characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. In this Review, we summarize recent progress in the field of pDC biology, focusing on the molecular mechanisms that regulate the development and functions of pDCs, the pathways involved in their sensing of pathogens and endogenous nucleic acids, their functions at mucosal sites, and their roles in infection, autoimmunity and cancer. PMID- 26160623 TI - Mentalization and Dialectical Behavior Therapy. AB - Dialectical Behavior Therapy (DBT) and Mentalization-Based Treatment (MBT) are two approaches to the treatment of borderline personality disorder (BPD). While DBT has the most empirical support, MBT has a small but significant evidence base. Dialectical behavior therapy synthesizes behaviorism, mindfulness, and dialectics, while MBT is conceptually anchored in psychoanalysis, attachment theory, cognitive neuroscience, and developmental psychopathology. While coming from strikingly different orientations, DBT and MBT therapists share more interventions and stances than one might suppose. The central purported active ingredient of MBT is the capacity to mentalize, which is crucial for the formation of secure attachment, and this ability is thought to be weak and unstable in individuals with borderline personality disorder. This article explores the question of whether or not mentalizing is already present in DBT practice, whether it would be compatible with DBT conceptually and practically, and whether a focus on mentalizing would be of use to the DBT therapists and their patients. PMID- 26160622 TI - Dialectical Behavior Therapy for Suicidal Latina Adolescents: Supplemental Dialectical Corollaries and Treatment Targets. AB - The primary aim of this paper is to describe extreme behavioral patterns that the authors have observed in treating Latina adolescents who are suicidal and their parents within the framework of dialectical behavior therapy (DBT). These extreme patterns, called dialectical corollaries, serve to supplement the adolescent/family dialectical dilemmas described by Rathus and Miller (2002) as part of dialectical behavior therapy for suicidal adolescents with borderline personality features. The dialectical corollaries proposed are "old school versus new school" and "overprotecting" versus "underprotecting," and they are described in-depth. We also identify specific treatment targets for each corollary and discuss therapeutic techniques aimed at achieving a synthesis between the polarities that characterize each corollary. Lastly, we suggest clinical strategies to use when therapists reach a therapeutic impasse with the parent adolescent dyad (i.e., dialectical failures). PMID- 26160624 TI - Towards the Development of an Effective Working Alliance: The Application of DBT Validation and Stylistic Strategies in the Adaptation of a Manualized Complex Trauma Group Treatment Program for Adolescents in Long-Term Detention. AB - The current paper details a case of adapting a manualized group therapy treatment for youths experiencing chronic stress. It was used for use with a highly traumatized and behaviorally disordered group of adolescents (ages 14 to 17 years) in long-term juvenile detention. The authors argue for a phasic approach to treatment for this population, with the goal of the essential, initial phase being the development of an authentic therapeutic alliance before other treatment goals are pursued. The authors provide clinical examples of liberally and patiently utilizing dialectical behavior therapy-framed acceptance-based strategies to achieve this therapeutic alliance, and only then naturally weaving in more traditional cognitive behavioral, change-oriented psychoeducational approaches successfully. Clinical and research implications for effective treatment of traumatized, detained youths are also discussed. PMID- 26160625 TI - Treatment of Hypertension: Favourable Effect of the Twice-Daily Compared to the Once-Daily (Evening) Administration of Perindopril and Losartan. AB - BACKGROUND/AIMS: Little is known about the effect of twice daily administration of same dose of ACE inhibitor and ARB on the diurnal/nocturnal blood pressure (BP) ratio. We aimed to assess the effect of two widely used long-acting drugs: perindopril and losartan in the treatment of hypertension comparing the once daily (evening) vs. twice-daily (morning and evening) administration with the same daily doses. METHODS: Untreated primary hypertensive patients without complaints (a total of 164: 65 men, 99 women, 55.7 +/- 13.7 years of age, 41-41 patients per treated groups) were selected with non-dipper phenomenon, estimated by diurnal index (DI) <10%. The effect of evening (8 mg perindopril or 100 mg losartan) vs morning and evening (4-4 mg perindopril or 50-50 mg losartan) administration was determined on a 14-day treatment by ABPM. RESULTS: The mean BP, the percent time elevation index, and the hyperbaric impact decreased in both drug groups. Significant difference was observed in the DI in the case of twice daily administration vs once-daily evening dosing. CONCLUSIONS: The twice-daily administration with the same daily dose of perindopril or losartan seems to be more effective compared to the once daily evening administration in eliminating the non-dipper phenomenon. According to some authors the non-dipping phenomenon increases cardiovascular risk, while others are of the opinion that the association of non-dipping with cardiovascular events does not necessarily mean that selective treatment of non-dipping improves cardiovascular outcomes. PMID- 26160627 TI - Ventricular Ectopy as a Modifiable Risk Factor for Heart Failure and Death: "Deja Vu All Over Again" May Be a Good Thing. PMID- 26160626 TI - Ventricular Ectopy as a Predictor of Heart Failure and Death. AB - BACKGROUND: Studies of patients presenting for catheter ablation suggest that premature ventricular contractions (PVCs) are a modifiable risk factor for congestive heart failure (CHF). The relationship among PVC frequency, incident CHF, and mortality in the general population remains unknown. OBJECTIVES: The goal of this study was to determine whether PVC frequency ascertained using a 24 h Holter monitor is a predictor of a decrease in the left ventricular ejection fraction (LVEF), incident CHF, and death in a population-based cohort. METHODS: We studied 1,139 Cardiovascular Health Study (CHS) participants who were randomly assigned to 24-h ambulatory electrocardiography (Holter) monitoring and who had a normal LVEF and no history of CHF. PVC frequency was quantified using Holter studies, and LVEF was measured from baseline and 5-year echocardiograms. Participants were followed for incident CHF and death. RESULTS: Those in the upper quartile versus the lowest quartile of PVC frequency had a multivariable adjusted, 3-fold greater odds of a 5-year decrease in LVEF (odds ratio [OR]: 3.10; 95% confidence interval [CI]: 1.42 to 6.77; p = 0.005), a 48% increased risk of incident CHF (HR: 1.48; 95% CI: 1.08 to 2.04; p = 0.02), and a 31% increased risk of death (HR: 1.31; 95% CI: 1.06 to 1.63; p = 0.01) during a median follow-up of >13 years. Similar statistically significant results were observed for PVCs analyzed as a continuous variable. The specificity for the 15 year risk of CHF exceeded 90% when PVCs included at least 0.7% of ventricular beats. The population-level risk for incident CHF attributed to PVCs was 8.1% (95% CI: 1.2% to 14.9%). CONCLUSIONS: In a population-based sample, a higher frequency of PVCs was associated with a decrease in LVEF, an increase in incident CHF, and increased mortality. Because of the capacity to prevent PVCs through medical or ablation therapy, PVCs may represent a modifiable risk factor for CHF and death. PMID- 26160628 TI - Impact of Side Branch Modeling on Computation of Endothelial Shear Stress in Coronary Artery Disease: Coronary Tree Reconstruction by Fusion of 3D Angiography and OCT. AB - BACKGROUND: Computational fluid dynamics allow virtual evaluation of coronary physiology and shear stress (SS). Most studies hitherto assumed the vessel as a single conduit without accounting for the flow through side branches. OBJECTIVES: This study sought to develop a new approach to reconstruct coronary geometry that also computes outgoing flow through side branches in hemodynamic and biomechanical calculations, using fusion of optical coherence tomography (OCT) and 3-dimensional (3D) angiography. METHODS: Twenty-one patients enrolled in the DOCTOR (Does Optical Coherence Tomography Optimize Revascularization) fusion study underwent OCT and 3D-angiography of the target vessel (9 left anterior descending, 2 left circumflex, 10 right coronary artery). Coronary 3D reconstruction was performed by fusion of OCT and angiography, creating a true anatomical tree model (TM) including the side branches, and a traditional single conduit model (SCM) disregarding the side branches. RESULTS: The distal coronary pressure to aortic pressure (Pd/Pa) ratio was significantly higher in TMs than in SCMs (0.904 vs. 0.842; p < 0.0001). Agreement between TM and SCM in identifying patients with a Pd/Pa ratio <=0.80 under basal flow conditions was only k = 0.417 (p = 0.019). Average SS was 4.64 Pascal lower in TMs than in SCMs (p < 0.0001), with marked differences in the point-per-point comparison, ranging from -60.71 to 7.47 Pascal. CONCLUSIONS: True anatomical TMs that take into account the flow through side branches are feasible for accurate hemodynamic and biomechanical calculations. Traditional SCMs underestimate Pd/Pa and are inaccurate for regional SS estimation. Implementation of TMs might improve the accuracy of SS and virtual fractional flow reserve calculations, thus improving the consistency of biomechanical studies. PMID- 26160629 TI - Ongoing Methodological Approaches to Improve the In Vivo Assessment of Local Coronary Blood Flow and Endothelial Shear Stress: The Devil Is in the Details. PMID- 26160631 TI - Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model. AB - BACKGROUND: Heme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post ischemic inflammation is unclear. OBJECTIVES: This study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model. METHODS: Murine ischemia was induced by 45 min of left anterior descending occlusion, followed by 24 h of reperfusion and functional as well as fluorescent-activated cell sorting analysis. Porcine hearts were subjected to 60 min of ischemia and 24h of reperfusion before hemodynamic and histologic analyses were performed. RESULTS: Human microvascular endothelial cells transfected with hHO-1 displayed an attenuated interleukin-6 and intercellular adhesion molecule 1 expression, resulting in reduced monocytic THP 1 cell recruitment in vitro. In murine left anterior descending occlusion and reperfusion, the post-ischemic influx of CD45(+) leukocytes, Ly-6G(+) neutrophils, and Ly-6C(high) monocytes was further exacerbated in HO-1-deficient hearts and reversed by rAAV.hHO-1 treatment. Conversely, in our porcine model of ischemia, the post-ischemic influx of myeloperoxidase-positive neutrophils and CD14(+) monocytes was reduced by 49% and 87% after rAAV.hHO-1 transduction, similar to hHO-1 transgenic pigs. Functionally, rAAV.hHO-1 and hHO-1 transgenic left ventricles displayed a smaller loss of ejection fraction than control animals. CONCLUSIONS: Whereas HO-1 deficiency exacerbates post-ischemic cardiac inflammation in mice, hHO-1 gene therapy attenuates inflammation after ischemia and reperfusion in murine and porcine hearts. Regional hHO-1 gene therapy provides cardioprotection in a pre-clinical porcine ischemia/reperfusion model. PMID- 26160630 TI - Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy. AB - BACKGROUND: Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. OBJECTIVES: This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. METHODS: Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. RESULTS: Compared with control subjects, VEGF B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. CONCLUSIONS: Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure. PMID- 26160632 TI - Revisiting Old Players in the Revitalized Field of Cardiovascular Gene Therapy. PMID- 26160633 TI - Transcatheter Therapies for the Treatment of Valvular and Paravalvular Regurgitation in Acquired and Congenital Valvular Heart Disease. AB - Transcatheter therapies in structural heart disease have evolved tremendously over the past 15 years. Since the introduction of the first balloon-expandable valves for stenotic lesions with implantation in the pulmonic position in 2000, treatment for valvular heart disease in the outflow position has become more refined, with newer-generation devices, alternative techniques, and novel access approaches. Recent efforts into the inflow position and regurgitant lesions, with transcatheter repair and replacement technologies, have expanded our potential to treat a broader, more heterogeneous patient population. The evolution of multimodality imaging has paralleled these developments. Three- and 4-dimensional visualization and concomitant use of novel technologies, such as fusion imaging, have supported technical growth, from pre-procedural planning and intraprocedural guidance, to assessment of acute results and follow-up. A multimodality approach has allowed operators to overcome many limitations of each modality and facilitated integration of a multidisciplinary team for treatment of this complex patient population. PMID- 26160635 TI - The Ever-Increasing Importance of a Professional Home. PMID- 26160634 TI - Utilization of and Adherence to Guideline-Recommended Lipid-Lowering Therapy After Acute Coronary Syndrome: Opportunities for Improvement. AB - In addition to aggressive lifestyle and nonlipid risk factor modification, statin therapy improves cardiovascular disease outcomes following acute coronary syndromes. Despite established benefits of treatment, contemporary registries reveal substantial underutilization of and nonadherence to statin therapy for secondary prevention. In randomized controlled trials investigating statin therapy, including moderate-intensity statin plus ezetimibe therapy, rates of nonadherence are reported in up to 40% of subjects. Durable strategies to address gaps in lipid lowering for secondary prevention are essential to maximize reduction in cardiovascular disease risk. PMID- 26160636 TI - Trends in Characteristics of CVD in Asia and Japan: The Importance of Epidemiological Studies and Beyond. PMID- 26160637 TI - Inpatient Cardiology Consultation: Lessons Learned During Fellowship. PMID- 26160638 TI - Prioritizing Proteomics Assay Development for Clinical Translation. PMID- 26160639 TI - Adenosine and Clinical Forms of Neurally-Mediated Syncope. PMID- 26160640 TI - Early Repolarization: A Risk Factor in Brugada Syndrome. PMID- 26160641 TI - Reply: Early Repolarization: A Risk Factor in Brugada Syndrome. PMID- 26160642 TI - Late Cardiac Death in Patients Undergoing Transcatheter Aortic Valve Replacement. PMID- 26160643 TI - Proof phenomenon as a function of the phenomenology of proving. AB - Kurt Godel wrote (1964, p. 272), after he had read Husserl, that the notion of objectivity raises a question: "the question of the objective existence of the objects of mathematical intuition (which, incidentally, is an exact replica of the question of the objective existence of the outer world)". This "exact replica" brings to mind the close analogy Husserl saw between our intuition of essences in Wesensschau and of physical objects in perception. What is it like to experience a mathematical proving process? What is the ontological status of a mathematical proof? Can computer assisted provers output a proof? Taking a naturalized world account, I will assess the relationship between mathematics, the physical world and consciousness by introducing a significant conceptual distinction between proving and proof. I will propose that proving is a phenomenological conscious experience. This experience involves a combination of what Kurt Godel called intuition, and what Husserl called intentionality. In contrast, proof is a function of that process - the mathematical phenomenon - that objectively self-presents a property in the world, and that results from a spatiotemporal unity being subject to the exact laws of nature. In this essay, I apply phenomenology to mathematical proving as a performance of consciousness, that is, a lived experience expressed and formalized in language, in which there is the possibility of formulating intersubjectively shareable meanings. PMID- 26160644 TI - Nontrivial quantum and quantum-like effects in biosystems: Unsolved questions and paradoxes. AB - Non-trivial quantum effects in biological systems are analyzed. Some unresolved issues and paradoxes related to quantum effects (Levinthal's paradox, the paradox of speed, and mechanisms of evolution) are addressed. It is concluded that the existence of non-trivial quantum effects is necessary for the functioning of living systems. In particular, it is demonstrated that classical mechanics cannot explain the stable work of the cell and any over-cell structures. The need for quantum effects is generated also by combinatorial problems of evolution. Their solution requires a priori information about the states of the evolving system, but within the framework of the classical theory it is not possible to explain mechanisms of its storage consistently. We also present essentials of so called quantum-like paradigm: sufficiently complex bio-systems process information by violating the laws of classical probability and information theory. Therefore the mathematical apparatus of quantum theory may have fruitful applications to describe behavior of bio-systems: from cells to brains, ecosystems and social systems. In quantum-like information biology it is not presumed that quantum information bio-processing is resulted from quantum physical processes in living organisms. Special experiments to test the role of quantum mechanics in living systems are suggested. This requires a detailed study of living systems on the level of individual atoms and molecules. Such monitoring of living systems in vivo can allow the identification of the real potentials of interaction between biologically important molecules. PMID- 26160645 TI - Epidural Anesthesia and Perioperative Hypotension. PMID- 26160646 TI - The Lawrence D. Dorr Surgical Techniques & Technologies Award: Conversion Total Hip Arthroplasty: Is it a Primary or Revision Hip Arthroplasty. AB - BACKGROUND: Total hip arthroplasty (THA) is an increasingly common procedure among elderly individuals. Although conversion THA is currently bundled in a diagnosis related group (DRG) with primary THA, no study has identified whether patients undergoing conversion THA better resemble patients undergoing primary THA or revision THA. The American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) database collects data from hospitals nationwide about preoperative characteristics, intraoperative factors, and 30-day postoperative complications. The purpose of our study was to use these variables in the ACS-NSQIP dataset to compare patients undergoing conversion THA to those undergoing primary and revision THA in order to ensure proper DRG classification of these procedures. METHODS: Between 2009-2014, the ACS-NSQIP database identified 2,009 conversion THA patients, 5,089 revision THA patients, and 67,854 primary THA patients. Univariate analysis was used to compare fifty-three preoperative, intraoperative, and postoperative variables among these groups. A conservative Bonferroni-adjusted P-value of .0003 was calculated, and a less conservative P-value of .01 was used for comparison. RESULTS: Seventeen variables exhibited a significant difference (P <= .0003) only between conversion and primary THA, one variable exhibited a difference only between conversion and revision THA, and three variables exhibited a difference between both conversion and primary THA, and conversion and revision THA. With P <= .01, twenty-three, zero, and six differences were observed, respectively. CONCLUSION: The disproportionate number of differences between conversion and primary THAs suggests that patients undergoing conversion THAs better resemble patients undergoing revision THAs. DRGs are traditionally comprised of procedures that have similar diagnoses and require comparable levels of resources from a hospital, so these results suggest that conversion THA should rather be bundled in the same DRG as revision THA. With hospitals emphasizing cost-containment strategies, this reclassification would be a step forward in improving the documentation of procedures in order to receive appropriate institutional reimbursement. PMID- 26160647 TI - WOMAC, EQ-5D and Knee Society Score Thresholds for Treatment Success After Total Knee Arthroplasty. AB - Our study aimed at developing clinical thresholds (cut-off scores) for the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index, EQ-5D and Knee Society Score for discriminating between patients with and without treatment success following total knee arthroplasty (TKA). We performed a retrospective analysis of 1055 patients 2 months after TKA and 765 patients 1 year after TKA. We considered treatment successful if the patient reported high levels of satisfaction and pain relief, functional increase, and a willingness to undergo the same procedure again. Based on this criterion we identified cut-off scores that will facilitate interpretation of the WOMAC, the EQ-5D and the KSS in TKA patients. PMID- 26160648 TI - Challenges in drug discovery for overcoming 'dysfunctional pain': an emerging category of chronic pain. AB - 'Dysfunctional pain', a type of chronic pain, is associated with a broad range of clinical disorders, including fibromyalgia, irritable bowel syndrome and interstitial cystitis. It is emerging as a serious issue due to the negative impact of inexplicable pain on quality of life, lack of effective therapies and health care cost. Although drug discovery efforts in pain research have so far focused primarily on inflammatory and neuropathic pain, this editorial attracts attention to dysfunctional pain research and discusses a possible fundamental framework for tackling this difficult issue. While dysfunctional pain is characterized by chronic widespread or regional pain symptoms and occurrence of pain amplification, underlying pathophysiologies remain to be identified. Thus, a pivotal step in future research would be the exploration of pathophysiological pathways, such as relevant molecular networks, which are responsible for dysfunctional pain. Utilization of developing technologies paves the way for the identification of underlying pathophysiologies and the development of effective drugs which would eventually solve the clinical issues associated with dysfunctional pain. PMID- 26160649 TI - Knee injury in a 12 year old girl. PMID- 26160650 TI - Exploratory cost-effectiveness analysis of cardiac resynchronization therapy with systematic device optimization vs. standard (non-systematic) optimization: a multinational economic evaluation. AB - BACKGROUND: Recent studies provide evidence of improved clinical benefits associated with cardiac resynchronization therapy (CRT) optimization. Our analysis explores the cost-effectiveness of systematically optimized (SO, 3 times a year) vs. non-systematically optimized (NSO, less than 3 times a year) CRT, whatever the echo optimization method used (manual or SonR(r) automatic). A longitudinal cohort model was developed to predict clinical and economic outcomes for SO vs. NSO strategies over 5 years. The analysis was performed from the payer perspective. Data from CLEAR study post-hoc analysis was used with 199 pts with CRT pacemaker (CRT-P). The main economic outcome measure was incremental cost effectiveness (ICER) expressed as cost per Quality Adjusted Life Years (QALY) gained. To assess the impact of data uncertainty, a sensitivity analysis was performed. The model also predicts outcomes for the two optimization strategies for CRT-D therapy vs. optimal medical treatment (OPT). RESULTS: At 1 year, ICERs for SO CRT vs. NSO CRT-P range between 22,226 (Spain) and 26,977 (Italy). Therefore, on the basis of a Willingness-To-Pay of 30,000 per QALY, the SO method develops into a cost effective strategy from 1 year, onwards. These favorable outcomes are supported by the sensitivity analysis. Systematic optimization of CRT-D might also improve the cost-effectiveness of this device therapy by 27 % to 30 % dependent on the country analyzed, at 5 years. CONCLUSIONS: Our economic evaluation shows promising health economic benefits associated with SO CRT. These preliminary findings need further confirmation. PMID- 26160651 TI - Evaluation of BLAST-based edge-weighting metrics used for homology inference with the Markov Clustering algorithm. AB - BACKGROUND: Clustering protein sequences according to inferred homology is a fundamental step in the analysis of many large data sets. Since the publication of the Markov Clustering (MCL) algorithm in 2002, it has been the centerpiece of several popular applications. Each of these approaches generates an undirected graph that represents sequences as nodes connected to each other by edges weighted with a BLAST-based metric. MCL is then used to infer clusters of homologous proteins by analyzing these graphs. The various approaches differ only by how they weight the edges, yet there has been very little direct examination of the relative performance of alternative edge-weighting metrics. This study compares the performance of four BLAST-based edge-weighting metrics: the bit score, bit score ratio (BSR), bit score over anchored length (BAL), and negative common log of the expectation value (NLE). Performance is tested using the Extended CEGMA KOGs (ECK) database, which we introduce here. RESULTS: All metrics performed similarly when analyzing full-length sequences, but dramatic differences emerged as progressively larger fractions of the test sequences were split into fragments. The BSR and BAL successfully rescued subsets of clusters by strengthening certain types of alignments between fragmented sequences, but also shifted the largest correct scores down near the range of scores generated from spurious alignments. This penalty outweighed the benefits in most test cases, and was greatly exacerbated by increasing the MCL inflation parameter, making these metrics less robust than the bit score or the more popular NLE. Notably, the bit score performed as well or better than the other three metrics in all scenarios. CONCLUSIONS: The results provide a strong case for use of the bit score, which appears to offer equivalent or superior performance to the more popular NLE. The insight that MCL-based clustering methods can be improved using a more tractable edge-weighting metric will greatly simplify future implementations. We demonstrate this with our own minimalist Python implementation: Porthos, which uses only standard libraries and can process a graph with 25 m + edges connecting the 60 k + KOG sequences in half a minute using less than half a gigabyte of memory. PMID- 26160652 TI - Paper-trail index: Can a metric that captures a paper's history of submission and rejection give insight into its value and encourage good authorship practices? PMID- 26160653 TI - The polymerase slips and PIPO exists. PMID- 26160655 TI - The European Histamine Research Society 44th Annual Meeting, May 6-9, 2015 Malaga, Spain. PMID- 26160656 TI - The impact of thrombin generation and rotation thromboelastometry on assessment of severity of factor XI deficiency. AB - The phenotype of bleeding in patients with severe FXI deficiency is unpredictable and unlike other bleeding disorders, it is not directly correlated with levels of FXI. In this study we analyzed whether the global coagulation assays can serve as a clinical tool in predicting bleeding tendency in patients with severe FXI deficiency undergoing surgery, taking into account the large inter-individual variability of FXI levels and genotypes. Thrombin generation (TG) was measured in 39 platelet-poor plasma with or without tissue factor (TF) and in the presence or absence of corn trypsin inhibitor (CTI). Rotation thromboelastometry (ROTEM) was performed with fresh whole blood of 26 patients applying NATEM and INTEM tests. TG induced by recalcification can distinguish between bleeding and non-bleeding patients with severe FXI deficiency particularly among those with FXI activity of 2-20IU/dl. The addition of TF or TF and CTI to the TG assay masked the ability to differentiate between XI activity, genotype as well as bleeding and non-bleeding patients. ROTEM assays failed to distinguish bleeding from non-bleeding patients but could do so between different FXI activity levels and genotypes. In conclusion, in the current study we found a sensitive tool to distinguish between bleeding and non-bleeding patients. In order to recommend TG as a predictive tool for treatment tailoring, a larger patient group is required. PMID- 26160654 TI - Presynaptic active zones in invertebrates and vertebrates. AB - The regulated release of neurotransmitter occurs via the fusion of synaptic vesicles (SVs) at specialized regions of the presynaptic membrane called active zones (AZs). These regions are defined by a cytoskeletal matrix assembled at AZs (CAZ), which functions to direct SVs toward docking and fusion sites and supports their maturation into the readily releasable pool. In addition, CAZ proteins localize voltage-gated Ca(2+) channels at SV release sites, bringing the fusion machinery in close proximity to the calcium source. Proteins of the CAZ therefore ensure that vesicle fusion is temporally and spatially organized, allowing for the precise and reliable release of neurotransmitter. Importantly, AZs are highly dynamic structures, supporting presynaptic remodeling, changes in neurotransmitter release efficacy, and thus presynaptic forms of plasticity. In this review, we discuss recent advances in the study of active zones, highlighting how the CAZ molecularly defines sites of neurotransmitter release, endocytic zones, and the integrity of synapses. PMID- 26160657 TI - The effects of fluid resuscitation according to PiCCO on the early stage of severe acute pancreatitis. AB - OBJECTIVES: To evaluate the therapeutic effect of early fluid resuscitation under the guidance of Pulse indicator Continuous Cardiac Output (PiCCO) on patients with severe acute pancreatitis (SAP). METHODS: Clinical data of 18 SAP patients (the study group), who had undergone fluid resuscitation under the guidance of PiCCO from October 2011 to October 2013, were analyzed prospectively. Clinical data of 25 cases (control group) who had undergone fluid resuscitation without the guidance of PiCCO from January 2009 to September 2011 were collected. Then, retrospective and prospective case-control study was carried out. RESULTS: During the first 6 h, 0-24 h, 24-48 h, and 0-72 h of admission, the study group received more volume of fluid than the control group. There were significantly faster decline of APACHE II score and the value of blood lactate in study group, as well as the length of ICU stay and the proportion of renal failure at 72 h of admission. According to the 2012 Atlanta classification, six cases in study group turned into moderate SAP (33.30%), significantly higher than the control group (8.00%) (p = 0.0049). The volume of fluid infusion and clinical parameters were linearly relative. CONCLUSIONS: The PiCCO device may be a useful adjunct for fluid resuscitation monitoring in patients with SAP in the early stage. Early fluid resuscitation under the guidance of PiCCO can improve tissue perfusion, reduce the SIRS persistence time and the length of ICU stay. This program did not increase the risk of respiratory failure and influence the mortality. PMID- 26160658 TI - [Supportive drugs for improved implant healing]. AB - BACKGROUND: Improvement of implant healing in orthopedic and trauma surgery serves to improve the life expectancy of the implant. Good primary stability by clamping is a prerequisite for secondary stability and for the actual integration and healing of the implant. RESULTS: Possible causes of implant loosening are abrasive particles, which arrive at non-integrated implants at the unsealed prosthesis-bone interface and provoke a macrophage-mediated foreign body reaction, resulting in periprosthetic osteolysis. Numerous animal studies have already described the use of bisphosphonates to inhibit osteolysis induced by abrasion and secondary instability. In patients with total knee arthroplasty, a decrease in prosthetic migration under the influence of bisphosphonates could be shown. The stimulation of bone formation around the implants and the resulting implant healing was demonstrated both in animal experiments for bone morphogenetic proteins (BMP) and in case reports for intermittent parathyroid hormone administration. CONCLUSION: By using supportive drugs, it is possible to achieve an improvement in the osseointegration of implants; thus, more rapid secondary stability and load-bearing are expected. PMID- 26160659 TI - Effect of a beta-Hydroxyphosphonate Analogue of L-Carnitine on Insulin-Sensitive and Insulin-Resistant 3T3-L1 Adipocytes. AB - This study investigated the effect of a beta-x200B;hydroxyphosphonate analog of L carnitine (L-CA) (CAS number: 1220955-x200B;20-3, Component: 1221068-91-2, C12H29NO4PI), (3-Hexanaminium, 1-(dimethoxyphosphinyl)-2-hydroxy-N,N,N,5 x200B;tetramethy-iodide (1:1), (2R, 3S)) on parameters related with type-2 diabetes in an in vitro model. Nontoxic concentrations of L-CA were assayed and compared to commercial L-carnitine effects. L-CA did not affect adipogenesis in normal cells, but an increment of TG accumulation was observed on insulin resistant adipocytes (80%) when compared with resistant control. L-CA also stimulated glucose analog 2-NBDG uptakes on insulin-resistant adipocytes in a similar way as insulin when compared to insulin-resistant cells. Our results show that the L-CA promoted insulin-like responses on insulin-resistant adipocytes without appreciable pro-adipogenic effect in sensitive adipocytes. PMID- 26160660 TI - Heterologous expression and characterization of CYP61A1 from dandruff-causing Malassezia globosa. AB - Malassezia globosa is pathogenic fungus that causes skin disorders including dandruff in humans. Many yeast cytochrome CYP enzymes are involved in the biosynthesis of sterols and are considered major targets of azole antifungal agents. Here, we report on the expression and characterization of the MGL_0310 gene product (CYP61A1), a sterol C-22 desaturase in M. globosa. The open reading frame of the CYP61A1 gene was amplified by PCR from M. globosa CBS 7966 genomic DNA and cloned into a pCW vector. The CYP61A1 gene was heterologously expressed in Escherichia coli and purified using a Ni(2+)-NTA affinity column. The purified CYP61A1 protein exhibited a CO-difference spectrum typical of CYPs with a maximum absorption at 452nm. Binding spectral titration with beta-sitosterol and campesterol demonstrated the type I binding mode with an increase at 411nm and a decrease at 432nm. The calculated Kd values are 5.4+/-0.6MUM and 6.1+/-1.0MUM for beta-sitosterol and campesterol, respectively. No metabolic product, however, was observed in the CYP61A1-supported enzyme reaction with these sterols. The purified CYP61A1 protein exhibited tight binding to azole agents, suggesting that this enzyme may be a target for the pathogenic M. globosa fungus. Moreover, several fatty acids were found to bind to CYP61A1, indicating that the architecture of the enzyme includes a relatively large active site space. This study provides new insight into the biosynthesis of fungal sterols in M. globosa and a basis for the development of antifungal as potential therapeutic agents to treat dandruff. PMID- 26160661 TI - Trace element concentration in fine particulate matter (PM2.5) and their bioavailability in different microenvironments in Agra, India: a case study. AB - Exposure to airborne particulate matter results in the deposition of millions of particle in the lung; consequently, there is need for monitoring them particularly in indoor environments. Case study was conducted in three different microenvironments, i.e., urban, rural and roadside to examine the elemental bioavailability in fine particulate matter and its potential health risk. The samples were collected on polytetrafluoroethylene filter paper with the help of fine particulate sampler during August-September, 2012. The average mass concentration of PM2.5 was 71.23 ug m(-3) (rural), 45.33 ug m(-3) (urban) and 36.71 ug m(-3) (roadside). Elements in PM2.5 were analyzed by inductively coupled plasma atomic emission spectroscopy. Percentage bioavailability was determined to know the amount of soluble fraction that is actually taken across the cell membrane through inhalation pathway. Cadmium and lead were found to have cancer risk in a risk evaluation using an Integrated Risk Information system. PMID- 26160662 TI - Floodplain forest succession reveals fluvial processes: A hydrogeomorphic model for temperate riparian woodlands. AB - River valley floodplains are physically-dynamic environments where fluvial processes determine habitat gradients for riparian vegetation. These zones support trees and shrubs whose life stages are adapted to specific habitat types and consequently forest composition and successional stage reflect the underlying hydrogeomorphic processes and history. In this study we investigated woodland vegetation composition, successional stage and habitat properties, and compared these with physically-based indicators of hydraulic processes. We thus sought to develop a hydrogeomorphic model to evaluate riparian woodland condition based on the spatial mosaic of successional phases of the floodplain forest. The study investigated free-flowing and dam-impacted reaches of the Kootenai and Flathead Rivers, in Idaho and Montana, USA and British Columbia, Canada. The analyses revealed strong correspondence between vegetation assessments and metrics of fluvial processes indicating morphodynamics (erosion and shear stress), inundation and depth to groundwater. The results indicated that common successional stages generally occupied similar hydraulic environments along the different river segments. Comparison of the spatial patterns between the free flowing and regulated reaches revealed greater deviation from the natural condition for the braided channel segment than for the meandering segment. This demonstrates the utility of the hydrogeomorphic approach and suggests that riparian woodlands along braided channels could have lower resilience than those along meandering channels and might be more vulnerable to influences such as from river damming or climate change. PMID- 26160663 TI - Degradation of Methyl Orange and Congo Red dyes by using TiO2 nanoparticles activated by the solar and the solar-like radiation. AB - In this study we used TiO2 nanoparticles as semiconductor photocatalysts for the degradation of Methyl Orange (MO) and Congo Red (CR) dyes in an aqueous solution. Since TiO2 particles become photocatalytically active by UV radiation, two sources of UV-A radiation were used - natural solar radiation which contains 3-5% UV-A and artificial, solar-like radiation, created by using a lamp. The optimal doses of TiO2 of 500 mg/L for the CR and 1500 mg/L for the MO degradation were determined in experiments with the lamp and were also used in degradation experiments with natural solar light. The efficiency of each process was determined by measuring the absorbance at two visible wavelengths, 466 nm for MO and 498 nm for CR, and the total organic carbon (TOC), i.e. decolorization and mineralization, respectively. In both cases, considerable potential for the degradation of CR and MO was observed - total decolorization of the solution was achieved within 30-60 min, while the TOC removal was in the range 60-90%. CR and MO solutions irradiated without TiO2 nanoparticles showed no observable changes in either decolorization or mineralization. Three different commercially available TiO2 nanoparticles were used: pure-phase anatase, pure-phase rutile, and mixed-phase preparation named Degussa P25. In terms of degradation kinetics, P25 TiO2 exhibited a photocatalytic activity superior to that of pure-phase anatase or rutile. The electric energy consumption per gram of removed TOC was determined. For nearly the same degradation effect, the consumption in the natural solar radiation experiment was more than 60 times lower than in the artificial solar-like radiation experiment. PMID- 26160664 TI - System dynamic modelling of industrial growth and landscape ecology in China. AB - With the rapid development of large industrial corridors in China, the landscape ecology of the country is currently being affected. Therefore, in this study, a system dynamic model with multi-dimensional nonlinear dynamic prediction function that considers industrial growth and landscape ecology is developed and verified to allow for more sustainable development. Firstly, relationships between industrial development and landscape ecology in China are examined, and five subsystems are then established: industry, population, urban economy, environment and landscape ecology. The main influencing factors are then examined for each subsystem to establish flow charts connecting those factors. Consequently, by connecting the subsystems, an overall industry growth and landscape ecology model is established. Using actual data and landscape index calculated based on GIS of the Ha-Da-Qi industrial corridor, a typical industrial corridor in China, over the period 2005-2009, the model is validated in terms of historical behaviour, logical structure and future prediction, where for 84.8% of the factors, the error rate of the model is less than 5%, the mean error rate of all factors is 2.96% and the error of the simulation test for the landscape ecology subsystem is less than 2%. Moreover, a model application has been made to consider the changes in landscape indices under four industrial development modes, and the optimal industrial growth plan has been examined for landscape ecological protection through the simulation prediction results over 2015-2020. PMID- 26160665 TI - The prion-like RNA-processing protein HNRPDL forms inherently toxic amyloid-like inclusion bodies in bacteria. AB - BACKGROUND: The formation of protein inclusions is connected to the onset of many human diseases. Human RNA binding proteins containing intrinsically disordered regions with an amino acid composition resembling those of yeast prion domains, like TDP-43 or FUS, are being found to aggregate in different neurodegenerative disorders. The structure of the intracellular inclusions formed by these proteins is still unclear and whether these deposits have an amyloid nature or not is a matter of debate. Recently, the aggregation of TDP-43 has been modelled in bacteria, showing that TDP-43 inclusion bodies (IBs) are amorphous but intrinsically neurotoxic. This observation raises the question of whether it is indeed the lack of an ordered structure in these human prion-like protein aggregates the underlying cause of their toxicity in different pathological states. RESULTS: Here we characterize the IBs formed by the human prion-like RNA processing protein HNRPDL. HNRPDL is linked to the development of limb-girdle muscular dystrophy 1G and shares domain architecture with TDP-43. We show that HNRPDL IBs display characteristic amyloid hallmarks, since these aggregates bind to amyloid dyes in vitro and inside the cell, they are enriched in intermolecular beta-sheet conformation and contain inner amyloid-like fibrillar structure. In addition, despite their ordered structure, HNRPDL IBs are highly neurotoxic. CONCLUSIONS: Our results suggest that at least some of the disorders caused by the aggregation of human prion-like proteins would rely on the formation of classical amyloid assemblies rather than being caused by amorphous aggregates. They also illustrate the power of microbial cell factories to model amyloid aggregation. PMID- 26160666 TI - Improved antitumor effect of paclitaxel administered in vivo as pH and glutathione-sensitive nanohydrogels. AB - Most antitumor drugs usually affect not only rapidly dividing cells, such as those in tumors, but also highly proliferative cells in normal tissues. This nonspecific drawback could be successfully solved by using nanocarriers as controlled drug delivery systems. In this work, pH and redox-responsive nanohydrogels (NG) based on N-isopropylacrilamide (NIPA), N-hydroxyethyl acrylamide (HEEA) 2-acrylamidoethyl carbamate (2AAECM) and N,N' cystaminebisacrylamide (CBA) as crosslinker were evaluated as bioreducible paclitaxel (PTX) nanocarriers for improving the accumulation of the drug within the tumor tissue and avoiding its conventional side effects. A single dose of PTX solution, unloaded-NHA 80/15/5CBA NG and PTX-loaded NHA 80/15/5-CBA NG (30 mg/kg PTX equivalent) were subcutaneously injected in female athymic nude mice bearing HeLa human tumor xenografts. PTX-loaded nanohydrogels showed higher antitumor activity than free PTX, as tumor evolution and Ki67 detection demonstrated. Histological tumor images revealed a higher content of defective mitotic figures and apoptotic bodies in PTX- treated tumors than in control or unloaded NG treated tumor samples. Nanohydrogels injection did not change any biochemical blood parameters, which means no liver or kidney damage after NG injection. However, differences in antioxidant defenses in MPS systems (liver, kidney and spleen) were observed among treatments, which may indicate an oxidative stress response after PTX injection. PMID- 26160667 TI - Hot-melt extrusion of polyvinyl alcohol for oral immediate release applications. AB - The primary purpose of this study was to process partially hydrolyzed PVOH grades (degree of hydroxylation (DH): 33-88%) via HME and to evaluate them as carrier for oral immediate release dosage forms in order to improve the release rate of poorly water soluble drugs (i.e., HCT and CEL) via the formulation of solid dispersions. PVOH grades (DH >70%) were able to solubilize HCT and CEL up to 15%, but required higher extrusion temperature, due to the crystalline nature of PVOH. The highest drug release rate was observed from hot-melt extruded PVOH samples with a high DH. While drug release from extrudates consisting of PVOH with a low DH was affected by ionic strength, there was no influence of pH and ionic strength on HCT release from PVOH samples with a higher DH. However, PVOH (DH >70%) required higher extrusion temperatures, which could hamper its application for thermosensitive drugs. Therefore, the secondary purpose was to investigate the effect of sorbitol, a water-soluble plasticizer, on the thermal properties of hot-melt extruded PVOH (DH >70%). The melting of PVOH/sorbitol mixture was required to establish molecular interactions between PVOH and sorbitol. These molecular interactions were reflected in the HME behavior: whereas an extrusion temperature of 180 degrees C was necessary to process physical mixtures of PVOH (DH >70%) and sorbitol, only 140 degrees C was necessary during re-extrusion (after quench cooling and cryomilling) of the PVOH/sorbitol mixture. In addition, the in vitro and in vivo dug release of plasticized PVOH was examined; whereas the CEL/PVO/sorbitol system was able to maintain supersaturation during in vitro dissolution (0.1N HCl) compared to Celebrex((r)), the in vivo pharmacokinetic parameters (AUC0-24h, Cmax and Tmax) were highly comparable. PMID- 26160668 TI - Release mechanisms of tacrolimus-loaded PLGA and PLA microspheres and immunosuppressive effects of the microspheres in a rat heart transplantation model. AB - The objective of this study was to elucidate the release and absorption mechanisms of tacrolimus loaded into microspheres composed of poly(lactic-co glycolic acid) (PLGA) and/or polylactic acid (PLA). Tacrolimus-loaded microspheres were prepared by the o/w emulsion solvent evaporation method. The entrapment efficiency correlated with the molecular weight of PLGA, and the glass transition temperature of PLGA microspheres was not decreased by the addition of tacrolimus. These results indicate that intermolecular interaction between tacrolimus and the polymer would affect the entrapment of tacrolimus in the microspheres. Tacrolimus was released with weight loss of the microspheres, and the dominant release mechanism of tacrolimus was considered to be erosion of the polymer rather than diffusion of the drug. The whole-blood concentration of tacrolimus in rats was maintained for at least 2 weeks after a single subcutaneous administration of the microspheres. The pharmacokinetic profile of tacrolimus following subcutaneous administration was similar to that following intramuscular administration, suggesting that the release and dissolution of tacrolimus, rather than the absorption of the dissolved tacrolimus, were rate limiting steps. Graft-survival time in a heart transplantation rat model was prolonged by the administration of tacrolimus-loaded microspheres. The microsphere formulation of tacrolimus would be expected to precisely control the blood concentration while maintaining the immunosuppressive effect of the drug. PMID- 26160669 TI - Variations in phthalate ester (PAE) accumulation and their formation mechanism in Chinese flowering cabbage (Brassica parachinensis L.) cultivars grown on PAE contaminated soils. AB - Phthalate ester (PAE) accumulation in crops poses great risks to human health and has aroused great concern. Here, we investigated variations in di-n butylphthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) accumulation by various Chinese flowering cabbage cultivars and revealed their variation mechanism. There were significant differences (p < 0.05) in shoot PAE concentrations of 28 cultivars. Moreover, significant positive correlations between DBP and DEHP concentrations in shoots of all cultivars indicated that they could be taken up simultaneously by various cultivars. Due to the lower translocation factor of low-PAE accumulator, its shoot PAEs concentrations were much lower than root compared to high-PAE accumulator. Further, subcellular distribution showed that PAE concentrations of root cell walls and organelles were much higher than those of shoots in low-PAE accumulator. Therefore, lower translocation from root to shoot and more PAEs accumulating in cell walls and organelles of root might act as main formation mechanism of low-PAE accumulator. PMID- 26160670 TI - Characterizing direct emissions of perfluoroalkyl substances from ongoing fluoropolymer production sources: A spatial trend study of Xiaoqing River, China. AB - The spatial trend of perfluoroalkyl substances (PFASs) along Xiaoqing River and its tributaries was studied to characterize isomer profiles and quantify emissions from fluoropolymer (FP) manufacturers in China. Substantially elevated ?PFAS concentrations downstream of tributary 4 demonstrated that the emissions from this FP manufacturer dominated total riverine discharges. Isomer profiles of perfluorooctanoic acid (PFOA) in water displayed a stepwise increase in percentage branched PFOA downstream of tributary 3 (14.0%) and 4 (22.7%) reflecting the importance of FP sources. Strong positive correlations between PFOA isomers in water downstream of tributary 4 indicated that isomer profiles were conserved from emission sources to the final reservoir. Riverine discharges of PFOA (23-67 t/yr) were in agreement with theoretical emission calculations from FP production (68 t/yr) whereas large discrepancies between the two methodologies were observed for perfluorobutanoic acid and perfluoropentanoic acid. Collectively, this study fills critical knowledge gaps for understanding ongoing global sources of PFASs. PMID- 26160671 TI - Uncertainties in observational data on organic aerosol: An annual perspective of sampling artifacts in Beijing, China. AB - Current understanding of organic aerosol (OA) is challenged by the large gap between simulation results and observational data. Based on six campaigns conducted in a representative mega city in China, this study provided an annual perspective of the uncertainties in observational OA data caused by sampling artifacts. Our results suggest that for the commonly-used sampling approach that involves collection of particles on a bare quartz filter, the positive artifact could result in a 20-40 % overestimation of OA concentrations. Based on an evaluation framework that includes four criteria, an activated carbon denuder was demonstrated to be able to effectively eliminate the positive artifact with a long useful time of at least one month, and hence it was recommended to be a good choice for routine measurement of carbonaceous aerosol. PMID- 26160672 TI - Factors controlling peat chemistry and vegetation composition in Sudbury peatlands after 30 years of pollution emission reductions. AB - The objective of this research was to assess factors controlling peat and plant chemistry, and vegetation composition in 18 peatlands surrounding Sudbury after more than 30 years of large (>95%) pollution emission reductions. Sites closer to the main Copper Cliff smelter had more humified peat and the surface horizons were greatly enriched in copper (Cu) and nickel (Ni). Copper and Ni concentrations in peat were significantly correlated with that in the plant tissue of Chamaedaphne calyculata. The pH of peat was the strongest determining factor for species richness, diversity, and community composition, although percent vascular plant cover was strongly negatively correlated with surface Cu and Ni concentrations in peat. Sphagnum frequency was also negatively related to peat Cu and Ni concentrations indicating sites close to Copper Cliff smelter remain adversely impacted by industrial activities. PMID- 26160674 TI - Converging and competing cues in the acquisition of syntactic structures: the conjoined agent intransitive. AB - In two studies we use a pointing task to explore developmentally the nature of the knowledge that underlies three- and four-year-old children's ability to assign meaning to the intransitive structure. The results suggest that early in development children are sensitive to a first-noun-as-causal-agent cue and animacy cues when interpreting conjoined agent intransitives. The same children, however, do not appear to rely exclusively on the number of nouns as a cue to structure meaning. The pattern of results indicates that children are processing a number of cues when inferring the meaning of the conjoined agent intransitive. These cues appear to be in competition with each other and the cue that receives the most activation is used to infer the meaning of the construction. Critically, these studies suggest that children's knowledge of syntactic structures forms a network of organization, such that knowledge of one structure can impact on interpretation of other structures. PMID- 26160673 TI - Testing the evolutionary conservation of vocal motoneurons in vertebrates. AB - Medullary motoneurons drive vocalization in many vertebrate lineages including fish, amphibians, birds, and mammals. The developmental history of vocal motoneuron populations in each of these lineages remains largely unknown. The highly conserved transcription factor Paired-like Homeobox 2b (Phox2b) is presumed to be expressed in all vertebrate hindbrain branchial motoneurons, including laryngeal motoneurons essential for vocalization in humans. We used immunohistochemistry and in situ hybridization to examine Phox2b protein and mRNA expression in caudal hindbrain and rostral spinal cord motoneuron populations in seven species across five chordate classes. Phox2b was present in motoneurons dedicated to sound production in mice and frogs (bullfrog, African clawed frog), but not those in bird (zebra finch) or bony fish (midshipman, channel catfish). Overall, the pattern of caudal medullary motoneuron Phox2b expression was conserved across vertebrates and similar to expression in sea lamprey. These observations suggest that motoneurons dedicated to sound production in vertebrates are not derived from a single developmentally or evolutionarily conserved progenitor pool. PMID- 26160675 TI - Bipolar and fixable probe targeting mitochondria to trace local depolarization via two-photon fluorescence lifetime imaging. AB - Polarization/depolarization levels of different single mitochondria in a cell are inhomogeneous, and always varying. Because depolarization is an indicator of mitochondrial dysfunction, tracing local depolarization is highly desirable. The existing fluorescent probes, however, are not well suited for this task, although they are applicable to assess the average polarization extents of whole cells. A multifunctional and bipolar probe MITFPS is thus developed, which includes a positively charged hydrophilic group and an environment sensitive fluorophore. In the probe design, the hydrophilic anchoring unit is chemically immobilized on a membrane protein, while the lipophilic fluorophore can be inserted deep into the phospholipid layer. The probe exhibits a sensitive response to the local variation in polarization by changing its fluorescence lifetime. MITFPS's applicability is confirmed by real-time in situ imaging of the complete process of an uncoupler-induced depolarization under a two-photon fluorescence lifetime microscope. The imaging result reveals that one mitochondrion could have quite different polarization than the other, even though they are in the same cell. PMID- 26160676 TI - Cesarean section and tissue adhesions. PMID- 26160677 TI - Host origin determines pH tolerance of Tritrichomonas foetus isolates from the feline gastrointestinal and bovine urogenital tracts. AB - The ability for protozoan parasites to tolerate pH fluctuations within their niche is critical for the establishment of infection and require the parasite to be capable of adapting to a distinct pH range. We used two host adapted Tritrichomonas foetus isolates, capable of infecting either the digestive tract (pH 5.3-6.6) of feline hosts or the reproductive tract (pH 7.4-7.8) of bovine hosts to address their adaptability to changing pH. Using flow cytometry, we investigated the pH tolerance of the bovine and feline T. foetus isolates over a range of physiologically relevant pH in vitro. Following exposure to mild acid stress (pH 6), the bovine T. foetus isolates showed a significant decrease in cell viability and increased cytoplasmic granularity (p-value < 0.003, p-value < 0.0002) compared to pH 7 and 8 (p-value > 0.7). In contrast, the feline genotype displayed an enhanced capacity to maintain cell morphology and viability (p-value > 0.05). Microscopic assessment revealed that following exposure to a weak acidic stress (pH 6), the bovine T. foetus transformed into rounded parasites with extended cell volumes and displays a decrease in viability. The higher tolerance for acidic extracellular environment of the feline isolate compared to the bovine isolate suggests that pH could be a critical factor in regulating T. foetus infections and host-specificity. PMID- 26160679 TI - Laboratory maintenance of the bacterial endosymbiont, Neorickettsia sp., through the life cycle of a digenean, Plagiorchis elegans. AB - The Digenea (Platyhelminthes: Trematoda) are a diverse and complex group of internal metazoan parasites. These parasites can serve as hosts to obligate intracellular bacteria belonging to the genus Neorickettsia (Family: Anaplasmataceae). Neorickettsiae persist within all stages of the fluke life cycle and thus are maintained through vertical transmission. However, the low prevalence of Neorickettsia in nature limits study of their transmission biology at different steps of digenean life cycles. To resolve this dilemma, we have developed for the first time a laboratory model allowing to maintain Neorickettsia sp. through the whole life cycle of a digenean, Plagiorchis elegans. The laboratory life cycle of P. elegans consists of a snail first intermediate host, Lymnaea stagnalis, an aquatic arthropod second intermediate host, Culex pipiens (mosquito larva), and a vertebrate definitive host, Mesocricetus auratus (Syrian hamster). This paper focuses on the development of the laboratory life cycle, as well as outlines its potential uses in studying the transmission biology of Neorickettsia and its evolutionary relationship within its digenean host. PMID- 26160678 TI - Schistosoma haematobium egg-induced bladder urothelial abnormalities dependent on p53 are modulated by host sex. AB - INTRODUCTION AND OBJECTIVE: The bladder urothelium changes dramatically during Schistosoma haematobium infection (urogenital schistosomiasis). These alterations include hyperplasia, ulceration, dysplasia, squamous metaplasia and frank carcinogenesis. Defining the pathways underpinning these urothelial responses will contribute to a deeper understanding of how S. haematobium egg expulsion, hematuria, and bladder cancer develop in humans. The tumor suppressor gene p53 is of particular interest, given its role in many cancers, including bladder cancer generally and schistosomal bladder cancer specifically. METHODS: Transgenic mice featuring tamoxifen-inducible Cre recombinase activity in cells expressing the urothelial-specific gene uroplakin-3a (Upk3a-GCE mice) were crossed with either TdTomato-floxed-EGFP reporter or p53-floxed mice. Mice were administered tamoxifen or vehicle control to induce excision of floxed genes. TdTomato-EGFP reporter mice were sacrificed and their bladders harvested, sectioned, and imaged by fluorescence microscopy. p53-floxed mice underwent bladder wall injection with S. haematobium eggs or vehicle controls. Three months later, mice were sacrificed and their bladders subjected to histological analysis (H&E staining). RESULTS: We first confirmed the phenotypic fidelity of Upk3a-GCE mice by crossing them with TdTomato-floxed-EGFP reporter mice and administering tamoxifen to their progeny. As expected, these progeny switched from TdTomato to EGFP expression in their bladder urothelium. Having confirmed the phenotype of Upk3a-GCE mice, we next crossed them to p53-floxed mice. The resulting progeny were given tamoxifen or vehicle control to render them urothelial p53-haploinsufficient or -intact, respectively. Then, we injected S. haematobium eggs or control vehicle into the bladder walls of these mice. Male p53-intact, egg-injected mice exhibited similar histological changes as their p53-haploinsufficient counterparts, including urothelial hyperplasia and ulceration. In contrast, female p53-intact, egg injected mice featured no urothelial ulceration, whereas their p53 haploinsufficient counterparts often had significant ulceration. CONCLUSIONS: Urothelial p53 signaling indeed seems to affect urothelial homeostasis during S. haematobium infection, albeit in a sex-specific manner. Ongoing work seeks to determine whether p53 mediates associated alterations in urothelial cell cycle status and frank carcinogenesis in the setting of urogenital schistosomiasis. PMID- 26160680 TI - Middle infratemporal fossa less invasive approach for radical resection of parapharyngeal tumors: surgical microanatomy and clinical application. AB - Surgery of the infratemporal fossa (ITF) and parapharyngeal area presents a formidable challenge to the surgeon due to its anatomical complexity and limited access. Conventional surgical approaches to these regions were often too invasive and necessitate sacrifice of normal function and anatomy. To describe a less invasive transcranial extradural approach to ITF parapharyngeal lesions and to determine its advantages, 17 patients with ITF parapharyngeal neoplasms who underwent tumor resection via this approach were enrolled in the study. All lesions located in the ITF precarotid parapharyngeal space were resected through a small operative corridor between the trigeminal nerve third branch (V3) and the temporomandibular joint (TMJ). Surgical outcomes and postoperative complications were evaluated. Pathological diagnosis included schwannoma in eight cases, paraganglioma in two cases, gangliocytoma in two cases, carcinosarcoma in one case, giant cell tumor in one case, pleomorphic adenoma in one case, chondroblastoma in one case, and juvenile angiofibroma in one case. Gross total resection was achieved in 12 cases, near-total and subtotal resection were in 3 and 2 cases, respectively. The most common postoperative complication was dysphagia. Surgical exposure can be customized from minimal (drilling of retrotrigeminal area) to maximal (full skeletonization of V3, removal of all structures lying lateral to the petrous segment of internal carotid artery) according to tumor size and location. Since the space between the V3 and TMJ is the main corridor of this approach, the key maneuver is the anterior translocation of V3 to obtain an acceptable surgical field. PMID- 26160681 TI - Click chemistry-mediated catalytic hairpin self-assembly for amplified and sensitive fluorescence detection of Cu(2+) in human serum. AB - Chemically reduced Cu(2+) triggers the ligation of alkynyl- and azido-modified DNA via click chemistry. Subsequently, the ligated DNA initiates cyclic assembly of two fluorescently quenched hairpin DNAs and generates significantly amplified fluorescence signals for highly sensitive detection of Cu(2+) in human serum samples. PMID- 26160682 TI - The Hippo pathway in colorectal cancer. AB - Colorectal cancer (CRC) is one the most frequently diagnosed neoplastic diseases worldwide. Currently, aside from traditional chemotherapy, advanced CRCs are treated with modern drugs targeting cellular components such as epithelial growth factor receptor (EGFR). Since up to 70% of metastasized CRCs are drug resistant, the description of recent progress in cellular homeostasis regulation may shed new light on the development of new molecular targets in cancer treatment. The Hippo pathway has recently become subject of intense investigations since it plays a crucial role in cell proliferation, differentiation, apoptosis and tumourigenesis. Components of the Hippo pathway are deregulated in various human malignancies, and expression levels of its major signal transducers were proposed as prognostic factors in colorectal cancer. In this review we focused on recent data regarding Hippo pathway, its up-stream signals and down-stream effectors. Hippo negatively regulates its major effectors, YAP1 and TAZ kinases, which act as transcriptional co-activators inducing expression of genes involved not only in tissue repair and proliferation but are also oncoproteins involved in tumour development and progression. The deregulation of Hippo pathway components was found in many malignancies. The interactions between Hippo and Wnt/beta-catenin signalling, crucial in the maintenance of cell homeostasis, have been described in relation to the control of intestinal stem cell proliferation and CRC development. The recently discovered positive feedback loop between activated YAP1 and increased EGFR/KRAS signalling found in oesophageal, ovarian and hepatocellular cancer has been related to the CRC progression and resistance to EGFR inhibitors during CRC therapy. PMID- 26160683 TI - Testosterone and breast cancer prevention. AB - Testosterone (T) is the most abundant biologically active hormone in women. Androgen receptors (AR) are located throughout the body including the breast where T decreases tissue proliferation. However, T can be aromatized to estradiol (E2), which increases proliferation and hence, breast cancer (BCA) risk. Increased aromatase expression and an imbalance in the ratio of stimulatory estrogens to protective androgens impacts breast homeostasis. Recent clinical data supports a role for T in BCA prevention. Women with symptoms of hormone deficiency treated with pharmacological doses of T alone or in combination with anastrozole (A), delivered by subcutaneous implants, had a reduced incidence of BCA. In addition, T combined with A effectively treated symptoms of hormone deficiency in BCA survivors and was not associated with recurrent disease. Most notably, T+A implants placed in breast tissue surrounding malignant tumors significantly reduced BCA tumor size, further supporting T direct antiproliferative, protective and therapeutic effect. PMID- 26160684 TI - Fertility-sparing management of gynecological cancers. AB - Fifteen to 21% of women diagnosed with genital tract tumors are younger than 40. Adequate counseling of these patients must be conducted to decide whether fertility-sparing treatment is allowed and what would be the oncological, fertility and obstetrical outcomes. We performed a comprehensive PubMed literature search using the terms "Uterine Cervical Neoplasms"[Mesh], "Trachelectomy", "Endometrial Neoplasms"[Mesh], "Ovarian Neoplasms"[Mesh] and "Fertility"[Mesh]. The following review reports available evidence for the conservative management of cervical, endometrial and ovarian cancer. Data regarding the selection of patients, surgical techniques, obstetrical issues and cancer prognosis are summarized. The level of evidence is low in most of the available reports. The therapeutic options presented in this paper should not therefore be considered as a standard of care. Nevertheless, fertility-sparing treatments of gynecological malignancies should be discussed in a multidisciplinary team and suggested to eligible patients who are younger than 40 and wish to become pregnant further. PMID- 26160685 TI - Extracellular protein analysis of activated sludge and their functions in wastewater treatment plant by shotgun proteomics. AB - In this work, proteins in extracellular polymeric substances extracted from anaerobic, anoxic and aerobic sludges of wastewater treatment plant (WWTP) were analyzed to probe their origins and functions. Extracellular proteins in WWTP sludges were identified using shotgun proteomics, and 130, 108 and 114 proteins in anaerobic, anoxic and aerobic samples were classified, respectively. Most proteins originated from cell and cell part, and their most major molecular functions were catalytic activity and binding activity. The results exhibited that the main roles of extracellular proteins in activated sludges were multivalence cations and organic molecules binding, as well as in catalysis and degradation. The catalytic activity proteins were more widespread in anaerobic sludge compared with those in anoxic and aerobic sludges. The structure difference between anaerobic and aerobic sludges could be associated with their catalytic activities proteins. The results also put forward a relation between the macro characteristics of activated sludges and micro functions of extracellular proteins in biological wastewater treatment process. PMID- 26160687 TI - T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response. AB - Endogenous tumor-specific T cells are detectable in patients with different tumor types including malignant melanoma (MM). They can control tumor growth, have impact on patient survival and correlate with improved clinical response to immune checkpoint therapy. Thus, they may represent a potent biomarker for respective treatment decisions. So far, major target antigens of endogenous MM reactive T cells have not been determined systematically. Instead, autoantibodies are discussed as surrogate parameter for MM-specific T cells. Throughout a period of more than 60 days after tumor resection, we therefore determined in 38 non metastasized primary MM patients and in healthy individuals by IFNgamma ELISpot and bead-based fluorescent multiplex assay major target antigens of spontaneous T cell and humoral responses using a broad panel of MM antigens and assessed the presence and suppressive impact of MM-reactive regulatory T cells (Tregs). We show that MM-reactive T cells are frequent in MM patients, transiently increase after tumor removal and are mostly directed against Melan-A/MART-1, Tyrosinase, NA17-A and p53. MM-specific Tregs were only detected in few patients and inhibited MM-reactive T cells particularly early after tumor resection. Tumor specific autoantibodies occurred in most patients, but did not correlate with T cell responses. Thus, endogenous antibodies may not be reliable surrogate parameters of MM-reactive T cells. PMID- 26160686 TI - Resistance to cellular autophagy by Mycobacterium tuberculosis Beijing strains. AB - Autophagy represents a key pathway in innate immune defense to restrict Mycobacterium tuberculosis growth inside host macrophages. Induction of autophagy has been shown to promote mycobacterial phagosome acidification and acquisition of lysosomal hydrolases, resulting in the elimination of intracellular M. tuberculosis reference strains such as H37Rv. The notorious Beijing genotype has been previously shown to be hyper-virulent and associated with increased survival in host cells and a high mortality rate in animal models, but the underlying mechanism that renders this family to have such advantages remains unclear. We hypothesize that autophagic control against M. tuberculosis Beijing strains may be altered. Here, we discovered that the Beijing strains can resist autophagic killing by host cells compared with that of the reference strain H37Rv and a strain belonging to the East African Indian genotype. Moreover, we have determined a possible underlying mechanism and found that the greater ability to evade autophagic elimination possessed by the Beijing strains stems from their higher capacity to inhibit autophagolysosome biogenesis upon autophagy induction. In summary, a previously unrecognized ability of the M. tuberculosis Beijing strains to evade host autophagy was identified, which may have important implications for tuberculosis treatment, especially in regions prevalent by the Beijing genotype. PMID- 26160688 TI - The impact of sleep restriction on daytime movement in typically developing children. AB - The current study investigated the link between poor sleep and ADHD symptomatology. The effects of extending versus restricting sleep on subjective (questionnaires) and objective (actigraphy) measures of daytime movement were examined in 25 typically developing children aged 8-12 years. Subjective measures demonstrated an increase in ADHD symptomology following sleep restriction, with follow-up analyses indicating that findings were due to poorer attention, not changes in hyperactivity. The results of actigraphy data indicated that there were no differences found for mean or median daytime activity, but the standard deviation of activity was found to be significantly higher following sleep restriction. Contrary to the popular belief that sleep restriction results in increased overall activity, this study instead found an increase in variability of activity. This suggests that a sleep-restricted child's activity level may appear as alternating periods of high and low activity levels throughout the day. PMID- 26160689 TI - Serial elongation, derotation and flexion (EDF) casting under general anesthesia and neuromuscular blocking drugs improve outcome in patients with juvenile scoliosis: preliminary results. AB - PURPOSE: Juvenile scoliosis (JS), among different types of spinal deformity, remains still a challenge for orthopedic surgeons. Elongation, derotation and flexion (EDF) casting technique is a custom-made thoracolumbar cast based on a three-dimensional correction concept. The primary objective of the present study was to measure changes on plain radiographs of patients with JS treated with EDF plaster technique. The second aim was to evaluate the effectiveness of the EDF plaster technique realized under general anesthesia (GA) and neuromuscular blocking drugs, i.e. curare, on the radiological curve correction. METHODS: A retrospective comparative case series study was performed in which were included forty-four skeletally immature patients. Three patient groups were selected. Group 1: EDF cast applied with patients awaken and no anesthesia; Group 2: EDF cast applied under GA without neuromuscular blocking drugs; Group 3: EDF cast applied under GA with neuromuscular blocking drugs. All the patients were treated with two serial EDF casts by 2 months and a half each. All measurements were taken from the radiographic exams. Cobb's angle; RVAD and Nash and Moe grade of rotation were assessed before and after applying the cast. Thirty-four (77.3 %) patients were followed up at least 24 months after removal of last EDF cast. RESULTS: Eighteen patients (3 males, 15 females) were included in Group 1, 12 (2 males, 10 females) in Group 2 and 14 (5 males, 9 females) in Group 3. Serial EDF casting was more effective at initial curve reduction and in preventing curve progression when applied under GA with neuromuscular blocking drugs, i.e. curare. RVAD and Nash and Moe score improved significantly in all groups of patients treated according to principles of EDF technique. During follow-up period, six patients required surgery in Group 1 (6/18; 33.3 %), 3 patients required surgery in Group 2 (3/12; 25 %) and 2 patients underwent surgery in Group 3 (2/14; 15 %). CONCLUSIONS: Preliminary results show EDF casting is effective in controlling the curve in both frontal (Cobb's angle) and transverse plane (rib vertebral angle and apical vertebral rotation degree). PMID- 26160690 TI - Is smoking a risk factor for lumbar disc herniation? AB - PURPOSE: To evaluate the association between cigarette smoking and lumbar disc herniation (LDH). METHODS: Cohort or case-control studies were identified by searches of several data bases, including Pubmed, Embase, Web of Science, and BIOSIS, for entries made up to December 2014. Data extraction was performed by two independent investigators. The data synthesis was performed using the random effects model. Subgroup analysis, sensitivity analyses, and assessment for publication bias were also performed. RESULTS: This systematic review included 12 studies-six each of cohort and case-control studies. The combined reported values showed that the relative risk of the association between smoking and LDH was 1.27 [95 % confidence interval (CI), 1.15-1.40] overall, 1.48 (95 % CI, 1.27-1.73) for case-control studies, and 1.17 (95 % CI, 1.05-1.30) for cohort studies. CONCLUSION: This systematic review demonstrates that smoking promotes the development of LDH. PMID- 26160691 TI - Micromagnet arrays for on-chip focusing, switching, and separation of superparamagnetic beads and single cells. AB - Nonlinear magnetophoresis (NLM) is a novel approach for on-chip transport and separation of superparamagnetic (SPM) beads, based on a travelling magnetic field wave generated by the combination of a micromagnet array (MMA) and an applied rotating magnetic field. Here, we present two novel MMA designs that allow SPM beads to be focused, sorted, and separated on-chip. Converging MMAs were used to rapidly collect the SPM beads from a large region of the chip and focus them into synchronised lines. We characterise the collection efficiency of the devices and demonstrate that they can facilitate on-chip analysis of populations of SPM beads using a single-point optical detector. The diverging MMAs were used to control the transport of the beads and to separate them based on their size. The separation efficiency of these devices was determined by the orientation of the magnetisation of the micromagnets relative to the external magnetic field and the size of the beads and relative to that of micromagnets. By controlling these parameters and the rotation of the external magnetic field we demonstrated the controlled transport of SPM bead-labelled single MDA-MB-231 cells. The use of these novel MMAs promises to allow magnetically-labelled cells to be efficiently isolated and then manipulated on-chip for analysis with high-resolution chemical and physical techniques. PMID- 26160692 TI - Erratum: Salmonella blood stream infections in a tertiary care setting in Ghana. PMID- 26160693 TI - Escherichia coli as host for membrane protein structure determination: a global analysis. AB - The structural biology of membrane proteins (MP) is hampered by the difficulty in producing and purifying them. A comprehensive analysis of protein databases revealed that 213 unique membrane protein structures have been obtained after production of the target protein in E. coli. The primary expression system used was the one based on the T7 RNA polymerase, followed by the arabinose and T5 promoter based expression systems. The C41lambda(DE3) and C43lambda(DE3) bacterial mutant hosts have contributed to 28% of non E. coli membrane protein structures. A large scale analysis of expression protocols demonstrated a preference for a combination of bacterial host-vector together with a bimodal distribution of induction temperature and of inducer concentration. Altogether our analysis provides a set of rules for the optimal use of bacterial expression systems in membrane protein production. PMID- 26160694 TI - Benign and Malignant Thyroid Incidentalomas Are Rare in Routine Clinical Practice: A Review of 97,908 Imaging Studies. AB - PURPOSE: Thyroid nodules incidentally identified on imaging are thought to contribute to the increasing incidence of thyroid cancer. We aim to determine the true rate of incidental thyroid nodule reporting, malignancy rates of these nodules, and to compare these findings with rates of detection by dedicated radiology review. METHODS: A cross-sectional analysis was done to determine the prevalence of thyroid nodules in radiologist reports by analyzing all reports for CT, PET, and MRI scans of the head, neck, and chest as well as neck ultrasounds performed at a tertiary care center from 2007 to 2012. Retrospective chart review was performed on patients with a reported thyroid nodule to determine clinical outcomes of these nodules. Radiology reports were compared with dedicated radiology review of 500 randomly selected CT scans from the study group to determine the difference between clinical reporting and actual prevalence of thyroid nodules. RESULTS: 97,908 imaging studies met inclusion criteria, and 387 (0.4%) thyroid incidentalomas were identified on radiology report. One hundred and sixty three (42.1%) of these nodules were worked up with fine-needle aspiration, diagnosing 27 thyroid cancers (0.03% of all studies, 7.0% of reported incidentalomas). The prevalence of incidentalomas clinically reported was 142/100,000 CT scans, 638/100,000 MRIs, 358/100,000 PET scans, and 6,594/100,000 ultrasounds. In contrast, review of CT scans screening for thyroid nodules had a prevalence of 10%. CONCLUSION: Routine clinical reporting of incidental thyroid nodules is far less common than on dedicated review. IMPACT: These data contradict the notion that incidentalomas contribute significantly to rising thyroid cancer rates. PMID- 26160695 TI - Sensorimotor Cortex Injection of Adeno-Associated Viral Vector Mediates Knockout of PTEN in Neurons of the Brain and Spinal Cord of Mice. AB - Cre/loxP-mediated inactivation of phosphatase and tensin homolog (PTEN) is proposed to be a promising therapeutic agent for promoting CNS and PNS regeneration. And adeno-associated virus (AAV) vector has been developed as an attractive gene delivery system with proven safety. In the present study, we investigated Cre/loxP-mediated knockout of PTEN in the sensorimotor cortex, hippocampus, and spinal cord in PTEN floxed mice by immunohistological analysis of PI3K/AKT/mTOR expression in neurons of the sensorimotor cortex, hippocampus, and spinal cord after sensorimotor cortex injection of AAV-Cre. Two weeks after injection of AAV-Cre, the sensorimotor cortex, hippocampus, and spinal cord were dissected and examined the expression of downstream molecules pAKT and pS6 of PI3K/AKT signaling pathway. The results showed that remote delivery of AAV-Cre through sensorimotor cortex injection mediated PTEN knockout in neurons of the sensorimotor cortex, hippocampus, and spinal cord. We propose sensorimotor cortex injection of AAV may provide a potential strategy of gene therapy for the CNS diseases. PMID- 26160696 TI - Raf-1 Kinase Inhibitory Protein (RKIP) Promotes Retinal Ganglion Cell Survival and Axonal Regeneration Following Optic Nerve Crush. AB - Raf-1 kinase inhibitory protein (RKIP), a member of the phosphatidylethanolamine binding protein (PEBP) family, plays an important role in neuronal apoptosis and cognitive deficits associated with neurodegenerative diseases. However, the biological function of RKIP in the retina is still unclear. Therefore, in the present study, we investigated the expression of RKIP in mouse retina following optic nerve crush (ONC) and evaluated the effects of RKIP on retinal ganglion cells (RGCs) apoptosis and axonal regeneration after ONC. Our results showed that the expression of RKIP was markedly decreased in the injured retina. Overexpression of RKIP inhibits RGC apoptosis and promotes axonal regeneration after ONC. Furthermore, overexpression of RKIP significantly increased the phosphorylation in extracellular signal-related kinase (ERK)1/2 and AKT in the injured retina. Taken together, these results suggest that RKIP promotes RGCs survival and axonal regeneration following ONC through promoting the ERK signaling pathway, implying that RKIP may serve as a potential molecular target for the treatment of glaucoma. PMID- 26160697 TI - The Effect of Waterpipe Tobacco Smoke Exposure on Learning and Memory Functions in the Rat Model. AB - Tobacco smoking is a global health hazard that kills about 5 million people annually. Waterpipe smoking is among the most popular methods of tobacco consumption worldwide. In this study, we investigated whether waterpipe smoking impairs learning and memory in the hippocampus, a question of special concern due to the particular popularity of waterpipe use among youth. Additionally, possible molecular targets for expected learning and memory impairment were determined. In this study, rats were exposed to waterpipe smoke (WTS) by whole body exposure 1 h * 5 days/week, for 1 month, and outcomes were compared to a control group exposed only to fresh air. Outcomes included spatial learning and memory using the radial arm water maze (RAWM) and oxidative stress biomarkers (catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio). We found that WTS exposure led to impaired short- and long-term memory. This impairment was accompanied by reduced hippocampal activity of catalase, SOD, GPx, GSH, and GSH/GSSG, elevated GSSG, thus marked changes in oxidative stress biomarkers. In conclusion, there is reason for concern that WTS exposure may impair cognitive ability. PMID- 26160698 TI - Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect. AB - INTRODUCTION: Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. OBJECTIVE: Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. METHODS: Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. RESULTS: The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). CONCLUSION: tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations. PMID- 26160699 TI - Corneal cross-linking as an adjuvant therapy in the management of recalcitrant deep stromal fungal keratitis: a randomized trial. PMID- 26160700 TI - Hematopoietic Cell and Renal Transplantation in Plasma Cell Dyscrasia Patients. AB - Gammopathies, multiple myeloma, and amyloidosis are plasma dyscrasias characterized by clonal proliferation and immunoglobulin overproduction. Renal impairment is the most common and serious complication with an incidence of 20 30% patients at the diagnosis. Kidney transplant has not been considered feasible in the presence of plasma dyscrasias because the immunosuppressive therapy may increase the risk of neoplasia progression, and paraproteins may affect the graft. However, recent advances in clinical management of multiple myeloma and other gammopathies allow considering kidney transplant as a possible alternative to dialysis. Numerous evidence indicates the direct relationship between hematological remission and renal function restoring. The combination of kidney and hematopoietic cell transplant has been reported as a promising approach to reestablish end-organ function and effectively treat the underlying disease. This review describes current protocols used to perform kidney transplantation in patients with plasma dyscrasias. PMID- 26160701 TI - Exposures in interventional radiology using Monte Carlo simulation coupled with virtual anthropomorphic phantoms. AB - In this work we investigated the way in which conversion coefficients from air kerma-area product for effective doses (CCE) and entrance skin doses (CCESD) in interventional radiology (IR) are affected by variations in the filtration, projection angle of the X-ray beam, lead curtain attached to the surgical table, and suspended shield lead glass in regular conditions of medical practice. Computer simulations were used to model an exposure scenario similar to a real IR room. The patient and the physician were represented by MASH virtual anthropomorphic phantoms, inserted in the MCNPX 2.7.0 radiation transport code. In all cases, the addition of copper filtration also increased the CCE and CCESD values. The highest CCE values were obtained for lateral, cranial and caudal projections. In these projections, the X-ray tube was located above the table, and more scattered radiation reached the middle and upper portions of the physician trunk, where most of the radiosensitive organs are located. Another important result of this study was to show that the physician's protection is 358% higher when the lead curtain and suspended shield lead glasses are used. The values of CCE and CCESD, presented in this study, are an important resource for calculation of effective doses and entrance skin doses in clinical practice. PMID- 26160702 TI - Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy. AB - PURPOSE: To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator. METHODS: The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors. RESULTS: A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes. CONCLUSIONS: The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions. PMID- 26160703 TI - Evaluation of population health short courses: implications for developing and evaluating population health professional development initiatives. AB - Population health as an approach to planning is key to improving the health and well-being of whole populations and to reduce inequities within and between population groups. The Victorian Department of Health North and West Metropolitan Region, in collaboration with The University of Melbourne (School of Population Health), have delivered four annual population health short courses. The short courses were designed to equip participants with knowledge and skills to implement population health approaches upon their return to their workplaces. For three consecutive years, online surveys (n=41) and semi-structured interviews (n=35), underpinned by participatory and realist evaluation approaches, were conducted to obtain the perceptions and experiences of the population health short course participants. Evaluation findings indicate that participants' understanding of population health concepts increased; however, there were mixed outcomes in assisting participants' implementation of population health approaches upon their return to their workplaces. A core list of perceived requirements, enablers and barriers emerged at an individual, organisational and system level as influencing the capability of participants to implement population health approaches. Evaluation recommendations and actions taken to revise short course iterations are presented, providing evidence that the evaluation approaches were appropriate and increased the use of evaluation learnings. Implications of evaluation findings for professional development practice (i.e. shift from a 'Course' as a one-off event to a Population Health 'Program' of inter-dependent components) and evaluation (i.e. participatory realist evaluation approaches) are presented. PMID- 26160704 TI - Endovascular treatment of ruptured intracranial aneurysms: Indications, techniques and results. AB - Rupture of an intracranial aneurysm is a diagnostic and therapeutic emergency. Occlusion of the aneurysm with coils is the first line treatment and should be performed promptly to avoid any further rupture, which carries a poor prognosis. Most aneurysms are accessible to this type of treatment. The risks of coiling, which are mostly thromboembolic and less commonly hemorrhagic due to peroperative rupture, are low. The use of stents or a flow diverter requires dual anti aggregation which increases their risks so that their use are restricted to specific situations such as dissecting aneurysms. Endovascular treatment is effective in the long and short term prevention of recurrent hemorrhage provided that patients are followed up by imaging, which allows possible early recanalization to be detected early and treated if necessary. PMID- 26160705 TI - Health-Related Quality of Life after Bariatric Surgery and its Correlation with Glycaemic Status in Hong Kong Chinese Adults. AB - BACKGROUND: To evaluate health-related quality of life (HRQOL) following bariatric surgery and its correlation with different glycaemic status in Hong Kong Chinese adults. MATERIALS AND METHODS: In 2002-2008, obese Chinese adults were recruited for bariatric surgery, undergoing laparoscopic adjustable gastric banding or laparoscopic sleeve gastrectomy. Patients were invited to complete the Chinese Hong Kong Medical Outcomes Study Short-Form Health Survey (SF-36) at baseline and at 1-year post operation. RESULTS: Sixty patients (60 % female) completed baseline and 1-year follow-up HRQOL assessments. Mean age was 38 years and mean BMI was 41.6 kg/m(2). At baseline, 30.0 % of patients had diabetes and 31.7 % prediabetes. Mean absolute weight reduction 1 year after bariatric surgery was 19.8 kg. Statistically significant improvements in SF-36 scores were demonstrated in all physical domains and in three of the four psychological domains. Greater body weight reduction was associated with greater improvements in certain physical domains postoperatively. After adjusting for co-variables, abnormal glucose tolerance was associated with greater improvements in five of the eight HRQOL domains. CONCLUSIONS: Bariatric surgery resulted in significant gains in HRQOL as well as significant reductions in body weight in obese Chinese adults. This study suggests that bariatric surgery offers greater HRQOL improvements in patients with prediabetes and diabetes compared with normoglycaemic individuals. PMID- 26160706 TI - Piperine Enhances the Protective Effect of Curcumin Against 3-NP Induced Neurotoxicity: Possible Neurotransmitters Modulation Mechanism. AB - 3-Nitropropionic acid (3-NP) is a fungal toxin well established model used for inducing symptoms of Huntington's disease. Curcumin a natural polyphenol has been reported to possess neuroprotective activity by decreasing oxidative stress. The aim of present study was to investigate neuroprotective effect of curcumin with piperine (bioavailability enhancer) against 3-NP induced neurotoxicity in rats. Administration of 3-NP (10 mg/kg for 21 days) showed loss in body weight, declined motor function and changes in biochemical (LPO, nitrite and glutathione level), neuroinflammatory (TNF-alpha and IL-1beta level) and neurochemical (DA, NE, 5-HT, DOPAC, 5-HIAA and HVA). Chronic treatment with curcumin (25 and 50 mg/kg) and curcumin (25 mg/kg) with piperine (2.5 mg/kg) once daily for 21 days prior to 3-NP administration. All the behavioral parameters were studied at 1st, 7th, 14th, and 21st day. On 22nd day all the animals was scarified and striatum was separated. Curcumin alone and combination (25 mg/kg) with piperine (2.5 mg/kg) showed beneficial effect against 3-NP induced motor deficit, biochemical and neurochemical abnormalities in rats. Piperine (2.5 mg/kg) with curcumin (25 mg/kg) significantly enhances its protective effect as compared with curcumin alone treated group. The results of the present study indicate that protective effect of curcumin potentiated in the presence of piperine (bioavailability enhancer) against 3-NP-induced behavioral and molecular alteration. PMID- 26160708 TI - Internalization as a mediator of the relationship between conformity to masculine norms and body image attitudes and behaviors among young men in Sweden, US, UK, and Australia. AB - We examined whether internalization of sociocultural body ideals mediated the relationship between conformity to masculine norms and drive for muscularity, leanness, and thinness in a sample of males from Sweden, US, UK, and Australia. Over six hundred young men [n=142 (Sweden); n=192 (US); n=141 (UK); n=160 (Australia)] completed an online survey that included assessments of masculine role norms, body image, and internalization of sociocultural body ideals. Path analyses confirmed internalization as a mediator between greater conformity to masculine norms and body image measures (drive for thinness, desire for leanness, and desire for muscularity) across the sample. However, significant cross-country differences in the strength of these mediation effects were found. Mediation effects among US, Australian, and Swedish males were comparable, whereas these effects were weaker in the UK sample. Findings confirmed the importance of internalization of sociocultural body ideals in the tested models. PMID- 26160707 TI - AMPK: energy sensor and survival mechanism in the ischemic heart. AB - AMP-activated protein kinase (AMPK) is a critical regulator of cellular metabolism and plays an important role in diabetes, cancer, and vascular disease. In the heart, AMPK activation is an essential component of the adaptive response to cardiomyocyte stress that occurs during myocardial ischemia. During ischemia reperfusion, AMPK activation modulates glucose and fatty acid metabolism, mitochondrial function, endoplasmic reticulum (ER) stress, autophagy, and apoptosis. Pharmacological activation of AMPK prevents myocardial necrosis and contractile dysfunction during ischemia-reperfusion and potentially represents a cardioprotective strategy for the treatment of myocardial infarction. This review discusses novel mechanisms of AMPK activation in the ischemic heart, the role of endogenous AMPK activation during ischemia, and the potential therapeutic applications for AMPK-directed therapy. PMID- 26160709 TI - Management of catecholamine-induced stunned myocardium--a case report. AB - Hypertensive, hypervolumic, and hemodilution therapy (triple-H therapy) is administered to patients with symptomatic cerebral vasospasm after intracranial aneurysm clipping. This therapy can sometimes result in cardiac dysfunction because of pharmacologically induced hyperadrenergic state. The diagnosis may be missed if blood pressure alone is monitored to guide triple-H therapy. In this report, we describe one such patient who developed cardiac failure after triple-H therapy. This was diagnosed by using a bioreactance noninvasive cardiac output monitoring. Continuous cardiac output monitoring by this technique facilitated treatment of cardiac failure with milrinone and dobutamine. At discharge, the patient had no neurologic deficits. PMID- 26160712 TI - Increased prevalence of comorbid conditions in women with uterine cancer. AB - OBJECTIVES: To compare comorbidities of women with uterine cancer (UC) to controls so as to aid in development of survivorship care plans and programs. METHODS: Retrospective cohort study using the University HealthSystem Consortium (UHC) database that compared women who had a hysterectomy for UC to women without UC undergoing hysterectomy. Frequencies and odds ratios (ORs) of 26 comorbidities were calculated. Mantel-Haenszel stratified ORs were determined to correct for different age distributions between the UC and control groups using UHC predetermined age groups. RESULTS: 23,227 patients in the dataset were included in the UC cohort, and 142,601 patients served as controls. Uncorrected ORs>=2 were found for hypertension, diabetes, obesity, congestive heart failure, pulmonary circulatory diseases, peripheral vascular disease, and renal failure. Higher ORs for UC remained significant after stratification by age for hypertension (OR=1.7), diabetes (OR=2.1), obesity (OR=3.3), congestive heart failure (OR=1.5), pulmonary circulatory disorders (OR=1.7), and renal failure (OR=1.2). CONCLUSIONS: Multiple comorbid conditions, specifically those related to the metabolic syndrome, were more prevalent in UC survivors than in the general population, and this difference persisted after adjustment for age. UC survivorship programs should plan to allocate resources to account for these differences in healthcare needs. PMID- 26160710 TI - A Novel, Stable, Estradiol-Stimulating, Osteogenic Yam Protein with Potential for the Treatment of Menopausal Syndrome. AB - A novel protein, designated as DOI, isolated from the Chinese yam (Dioscorea opposita Thunb.) could be the first protein drug for the treatment of menopausal syndrome and an alternative to hormone replacement therapy (HRT), which is known to have undesirable side effects. DOI is an acid- and thermo-stable protein with a distinctive N-terminal sequence Gly-Ile-Gly-Lys-Ile-Thr-Thr-Tyr-Trp-Gly-Gln-Tyr Ser-Asp-Glu-Pro-Ser-Leu-Thr-Glu. DOI was found to stimulate estradiol biosynthesis in rat ovarian granulosa cells; induce estradiol and progesterone secretion in 16- to 18-month-old female Sprague Dawley rats by upregulating expressions of follicle-stimulating hormone receptor and ovarian aromatase; counteract the progression of osteoporosis and augment bone mineral density; and improve cognitive functioning by upregulating protein expressions of brain derived neurotrophic factor and TrkB receptors in the prefrontal cortex. Furthermore, DOI did not stimulate the proliferation of breast cancer and ovarian cancer cells, which suggest it could be a more efficacious and safer alternative to HRT. PMID- 26160713 TI - Hypertriglyceridemia: a possible diagnostic marker of disease severity in visceral leishmaniasis. AB - PURPOSE: Visceral leishmaniasis (VL), a protozoan disease, is 100% fatal if left untreated. Anemia is common in VL which plays a role in expression of clinically overt VL disease. Laboratory clues are scarce for strengthening clinical suspicion for severity in VL. Hypertriglyceridemia has emerged as a new concept for the diagnosis and prognosis in VL. The present study is aimed at correlating the magnitude of hypertriglyceridemia with the severity in VL. MATERIALS AND METHODS: A retrospective case-control study was conducted between January 2012 to December 2013 among 124 patients coming for treatment from VL endemic areas, who had fever of more than 15 days and did not respond to antimalarials and antibiotics. The parasitologically confirmed VL cases (n = 87) were categorized as mild/moderate (n = 60) and severe (n = 27) groups according to WHO classification for anemia and parasite burden. Serum triglycerides were assayed in VL groups along with controls (n = 37). RESULTS: Serum triglyceride level was significantly higher in VL than controls [mean values were 173.50 +/- 47.67 versus 127.1 +/- 53.79 mg/dl, respectively (p < 0.0001)]. Triglyceride level was significantly higher in severe than in mild/moderate group of VL [211.3 +/- 50.2 mg/dl versus 134 +/- 45.09 mg/dl, respectively (p < 0.0001)]. Hypertriglyceridemia (>161.7 mg/dl) was noted in all severe VL patients, compared to 31.66% of mild or moderate group (p < 0.0001). There was no significant difference between mild/moderate VL and controls. CONCLUSIONS: It is hypothesized that hypertriglyceridemia could be of additional diagnostic benefit to assess the probability and severity of VL in endemic areas. PMID- 26160714 TI - Laparoscopic versus open distal pancreatectomy for benign or premalignant pancreatic neoplasms: a two-center comparative study. AB - OBJECTIVE: To compare the peri-operative outcomes for laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) for benign or premalignant pancreatic neoplasms in two institutions. METHODS: This prospective comparative study included 91 consecutive patients who underwent LDP (n=45) or ODP (n=46) from Jan. 2010 to Dec. 2012. Demographics, intra-operative characteristics, and post-operative outcomes were compared. RESULTS: The median operating time in the LDP group was (158.7+/-38.3) min compared with (92.2+/ 24.1) min in the ODP group (P<0.001). Patients had lower blood loss in LDP than in the ODP ((122.6+/-61.1) ml vs. (203.1+/-84.8) ml, P<0.001). The rates of splenic conservation between the LDP and ODP groups were similar (53.3% vs. 47.8%, P=0.35). All spleen-preserving distal pancreatectomies were conducted with vessel preservation. LDP also demonstrated better post-operative outcomes. The time to oral intake and normal daily activities was faster in the LDP group than in the ODP group ((1.6+/-0.5) d vs. (3.2+/-0.7) d, P<0.01; (1.8+/-0.4) d vs. (2.1+/-0.6) d, P=0.02, respectively), and the post-operative length of hospital stay in LDP was shorter than that in ODP ((7.9+/-3.8) d vs. (11.9+/-5.8) d, P=0.006). No difference in tumor size ((4.7+/-3.2) cm vs. (4.5+/-1.8) cm, P=0.77) or overall pancreatic fistula rate (15.6% vs. 19.6%, P=0.62) was found between the groups, while the overall post-operative complication rate was lower in the LDP group (26.7% vs. 47.8%, P=0.04). CONCLUSIONS: LDP is safe and effective for benign or premalignant pancreatic neoplasms, featuring lower blood loss and substantially faster recovery. PMID- 26160715 TI - Pure total flavonoids from Citrus paradisi Macfadyen act synergistically with arsenic trioxide in inducing apoptosis of Kasumi-1 leukemia cells in vitro. AB - To investigate the potential effects of pure total flavonoid compounds (PTFCs) from Citrus paradisi Macfadyen separately or combined with arsenic trioxide on the proliferation of human myeloid leukemia cells and the mechanisms underlying the action of PTFCs. The effects of PTFCs separately or combined with arsenic trioxide on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), fluorescence microscopy, and flow cytometry. Their effects on the expression levels of apoptosis-related regulators were determined by Western blot assay. PTFCs combined with arsenic trioxide significantly inhibited the growth of Kasumi-1 cells, and apoptosis was confirmed by flow cytometry analysis. Hoechst 33258 staining showed more significant morphological changes and more apoptosis following the combined treatment. Western blots showed changes in the expression of genes for poly ADP-ribose polymerase (PARP), caspase 3/9, and P65. The results indicated that PTFCs separately or combined with arsenic trioxide inhibited proliferation of leukemia cells in vitro and induced their apoptosis by modulating the expression of apoptosis-related regulator genes. PMID- 26160716 TI - A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine. AB - Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose (13)C sodium acetate ((13)C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of (13)CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT((r)) L100-55 on gelatin capsules and also on DRcaps((r)). Test results demonstrated that DRcaps((r)) coated with EUDRAGIT((r)) L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine. PMID- 26160717 TI - Bamboo leaf extract improves spatial learning ability in a rat model with senile dementia. AB - Senile dementia (SD) is a syndrome characterized by progressive neurological deterioration. Treatment for the disease is still under investigation. Bamboo leaf extract (B-extract) has been known for its biological efficacy in anti oxidant and anti-cancer activities. However, study on B-extract for its protection against dementia is very limited. The effect of B-extract on a rat model with SD was examined. B-extract improved spatial learning ability of the dementia rats. The hippocampus of dementia model rats showed reduced levels of acetylcholine (ACh), epinephrine (E), norepinephrine (NE), and dopamine (DA), and increased activities of acetylcholine esterase (AChE) and monoamine oxidase (MAO). Treatment with B-extract 20 mg/(kg.d) for 7 weeks significantly inhibited the enzyme activity compared with untreated dementia rats, and raised the levels of ACh, E, and DA in the hippocampus. In addition, treatment with B-extract elevated the level of gamma-aminobutyric acid (GABA), but reduced the level of glutamate (Glu) in the brain. These data suggest that B-extract might be a potential drug in treating impairment of spatial memory in dementia rats by regulating the central neurotransmitter function. PMID- 26160718 TI - Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals. AB - Chlorogenic acid (CGA), a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen (AP)-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase (ALT/AST) in vivo. The effect of CGA on cytochrome P450 (CYP) enzymatic (CYP2E1, CYP1A2, and CYP3A4) activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased mRNA expression of peroxiredoxin (Prx) 1, 2, 3, 5, 6, epoxide hydrolase (Ephx) 2, and polymerase (RNA) II (DNA directed) polypeptide K (Polr2k), and nuclear factor erythroid-2-related factor 2 (Nrf2). In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury. PMID- 26160719 TI - Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: a meta-analysis. AB - OBJECTIVE: The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. METHODS: Searches of PubMed and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. RESULTS: A total of 22 studies with 1492 subjects were included in our research. We identified: (1) a reduction in bone mineral density at lumbar spine (standardized mean difference (SMD)=-0.30, 95% confidence interval (CI) [-0.61, -0.05]), trochanter (mean difference (MD)=-0.07, 95% CI [-0.10, -0.05]), femoral neck (MD=-0.05, 95% CI [-0.09, -0.02]), and total body bone mineral density (MD=-0.33, 95% CI [-0.51, -0.15]); (2) a reduction in 25-hydroxyvitamin D (MD=-3.37, 95% CI [-5.94, -0.80]) and an increase in serum alkaline phosphatase (SMD=0.71, 95% CI [0.38, 1.05]); (3) no significant changes in serum parathyroid hormone, calcium, or phosphorus. CONCLUSIONS: Our meta analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children. PMID- 26160720 TI - Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma. AB - OBJECTIVE: Airway inflammation and airway hyper-responsiveness (AHR) are principle pathological manifestations of asthma. Cluster of differentiation 69 (CD69) is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody (mAb) on the pathophysiology of a mouse model of asthma. METHODS: A murine model of ovalbumin (OVA)-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 MUg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1% (0.01 g/ml) OVA on Days 24, 25, and 26. Anti-CD69 mAb or isotype IgG was injected intraperitoneally after OVA challenge; dexamethasone (DXM) was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) in bronchoalveolar lavage fluid (BALF) were also assayed as indices of airway inflammation on Day 28 following OVA injection. RESULTS: Pretreatment with DXM together with anti-CD69 mAb treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti CD69 mAb did not alter the concentration of BALF GM-CSF. CONCLUSIONS: Anti-CD69 mAb treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation. PMID- 26160721 TI - Correlation analysis of gene polymorphisms and beta-lactam allergy. AB - A total of 64 patients with beta-lactam allergy and 30 control subjects were enrolled in a case-control study. This study is aimed to analyze the relationship between beta-lactam allergy and 10 single nucleotide polymorphisms (SNPs) in interleukin-10 (IL-10), IL-13, IL-4Ralpha, high-affinity immunoglobulin E receptor beta chain (FcepsilonRIbeta), interferon gamma receptor 2 (IFNGR2), and CYP3A4, and within the Han Chinese population of Northwest China. Genotyping for the SNPs was conducted using the Sequenom MassARRAY((r)) platform. SPSS 17.0 was employed to analyze the statistical data and SHEsis was used to perform the haplotype reconstruction and analyze linkage disequilibrium of SNPs of IL-10 and IL-13. The results showed that the genotype distribution of CYP3A4 rs2242480/CT differed significantly between case and control groups of males (P=0.022; odds ratio (OR)=0.167, 95% confidence interval (CI): 0.032-0.867). Further analysis showed that CCA, CCG, and TAA haplotypes of IL-10 had no significant correlation in patients with beta-lactam allergy. The correlation between CCT and CAC haplotypes of IL-13 and beta-lactam allergy needs to be further studied. The analysis did not reveal any differences in the distribution of others gene polymorphisms between cases and controls. PMID- 26160722 TI - Diagnosis and treatment of allergic diseases in Zhejiang Province: a cross sectional survey. AB - BACKGROUND: The specialty of allergy developed quickly in western countries because of the rapid increase of allergic diseases, whereas it developed relatively slowly in China. The prevalence of allergen sensitization and allergic diseases in Zhejiang Province of China is high and improving the medical services for these diseases is critically needed. OBJECTIVE: To investigate the working status of the diagnosis and treatment of allergic diseases, including doctor resources, diagnostic methods, and allergen-specific immunotherapy in patients of Zhejiang Province, and to provide instructions for the strategic development of subspecialties of allergic diseases. METHODS: First we defined the doctors who treat allergic diseases, and designed a comprehensive questionnaire to collect personal and hospital information for these doctors. The questionnaires were distributed to hospitals with different ranks and from different areas in the province. The general condition of doctor's resources, carryout of diagnostic methods, and allergen-specific immunotherapy were described and variations in the different specialties, hospitals, and areas were further analyzed. RESULTS: Doctors in their thirties with bachelor's degrees were the mainstream for diagnosing and treating allergic diseases. The main specialties of the doctor resources were the specialties of Ear, Nose and Throat (ENT), Respirology, Pediatrics, and Dermatology. The Pediatrics specialty had a more reasonable infrastructure of doctor resources with more young doctors working in this subspecialty. The development of allergy subspecialty varied within hospitals at different levels or from different areas. The carryout of the skin prick test (SPT), serum specific IgE (ssIgE), and subcutaneous immunotherapy (SCIT) was best performed in provincial hospitals, while sublingual immunotherapy (SLIT) was prescribed most commonly in municipal hospitals. The performance of SPT and ssIgE in Hangzhou, Jiaxing, and Wenzhou areas was much better than that in other places. The performance of SCIT and SLIT was best in Wenzhou. CONCLUSIONS: Our survey revealed a very initial and unbalanced development for the allergy subspecialty in Zhejiang Province. Doctor resources for allergic diseases were mainly from the specialties of ENT, Respirology, and Pediatrics, and the performance of diagnosis and treatment was mainly focused on provincial and municipal hospitals. Continuous education of allergies could be extended to primary healthcare centers and more efforts should be directed to those areas with poor medical resources. PMID- 26160723 TI - Sharing intimacy in "open" intensive care units. AB - PURPOSE: Opening intensive care units (ICUs) is particularly relevant because of a new Swiss law granting the relatives of patients without decision-making capability a central role in medical decisions. The main objectives of the study were to assess how the presence of relatives is viewed by patients, health care providers, and relatives themselves and to evaluate the perception of the level of intrusiveness into the personal sphere during admission. MATERIAL AND METHODS: In a longitudinal and prospective design, qualitative questionnaires were submitted concomitantly to patients, relatives, and health care providers consecutively over a 6-month period. The study was conducted in the 4 ICUs of the public hospitals of Canton Ticino (Switzerland). RESULTS: The questionnaires collected from patients, relatives, and health care providers were 176, 173, and 134, respectively. The analysis of the answers of 120 patient-relative pairs showed consistent results (P < .0001), whereas those of health care providers were significantly different (P < .0001), regarding both the usefulness of opening ICUs to patient relatives and what was stressful during admission. CONCLUSIONS: Relatives in these "open" ICUs share a great deal of intimacy with the patients. Their presence and the deriving benefits were seen as very positive by patients and relatives themselves. Skepticism, instead, prevailed among health care providers. PMID- 26160725 TI - Sexual function in cervical cancer patients: Psychometric properties and performance of a Chinese version of the Female Sexual Function Index. AB - PURPOSE: This study aimed to examine the psychometric properties and performance of a Chinese version of the Female Sexual Function Index (FSFI) among a sample of Chinese women with cervical cancer. METHODS: A cross-sectional survey design was used. The respondents included 215 women with cervical cancer in an oncology hospital in China. A translated Chinese version of the FSFI was used to investigate their sexual functioning. Psychometric testing included internal consistency reliability (Cronbach's alpha coefficient and item-total correlations), test-retest reliability, construct validity (principal component analysis via oblique rotation and confirmatory factor analysis), and variability (floor and ceiling effects). RESULTS: The mean score of the total scale was 20.65 +/- 4.77. The Cronbach values were .94 for the total scale, .72-.90 for the domains. Test-retest correlation coefficients over 2-4 weeks were .84 (p < .05) for the total scale, .68-.83 for the subscales. Item-total correlation coefficients ranged between .47 and .83 (p < .05). A five-factor model was identified via principal component analysis and established by confirmatory factor analysis, including desire/arousal, lubrication, orgasm, satisfaction, and pain. There was no evidence of floor or ceiling effects. CONCLUSIONS: With good psychometric properties similar to its original English version, this Chinese version of the FSFI is demonstrated to be a reliable and valid instrument that can be used to assess sexual functioning of women with cervical cancer in China. Future research is still needed to confirm its psychometric properties and performance among a large sample. PMID- 26160726 TI - Megaesophagus due to achalasia. PMID- 26160724 TI - Oestrogen action and male fertility: experimental and clinical findings. AB - A proper balance between androgen and oestrogen is fundamental for normal male reproductive development and function in both animals and humans. This balance is governed by the cytochrome P450 aromatase, which is expressed also under spatio temporal control. Oestrogen receptors ERalpha and/or ERbeta, together with the membrane-associated G-protein-coupled functional ER (GPER), mediate the effects of oestrogen in the testis. Oestrogen action in male reproduction is more complex than previously predicted. The androgen/oestrogen balance and its regulation in the masculinisation programming window (MPW) during foetal life is the most critical period for the development of the male reproductive system. If this balance is impaired during the MPW, the male reproductive system may be negatively affected. Recent data from genetically modified mice and human infertile patients have shown that oestrogens may promote the engulfment of live Leydig cells by macrophages leading to male infertility. We also discuss recent data on environmental oestrogen exposure in men and rodents, where a rodent-human distinction is crucial and analyse some aspects of male fertility potentially related to impaired oestrogen/androgen balance. PMID- 26160728 TI - Corticosteroid exposure in pediatric acute respiratory distress syndrome. AB - PURPOSE: Use of systemic corticosteroids in acute respiratory distress syndrome (ARDS) remains controversial, and studies in children are lacking. METHODS: We performed an observational, single-center study in a prospectively enrolled cohort of children meeting criteria for ARDS (both Berlin 2012 and AECC 1994 acute lung injury) and pediatric ARDS (PARDS, as defined by PALICC 2015). Comprehensive analysis of corticosteroid utilization was planned, and detailed information collected on corticosteroid use, timing, treatment duration, and cumulative dose while mechanically ventilated. We assessed the association between corticosteroid exposure >24 h and outcomes. RESULTS: Of the 283 children with PARDS (37 deaths, 13%), 169 (60%) received corticosteroids for >24 h while ventilated: 51% hydrocortisone, 41% methylprednisolone, 5% dexamethasone, 3% combination of corticosteroids. Corticosteroid exposure >24 h was associated with increased mortality, fewer ventilator-free days at 28 days (VFD), and longer duration of ventilation in survivors in unadjusted analyses (all p < 0.05). Multivariate and propensity score adjusted analyses confirmed independent association of corticosteroid exposure with fewer VFD and longer duration of ventilation in survivors, but not with mortality. In planned analyses of high risk subgroups, no benefit was seen with corticosteroids exposure, with fewer VFD associated with corticosteroid exposure >24 h in patients with >=3 organ failures and immunocompromised patients. CONCLUSIONS: Corticosteroid exposure >24 h was independently associated with fewer VFD and longer duration of ventilation in survivors, even after adjustment for key potential confounders, including severity of illness, oxygenation index, immunocompromised status, and number of organ failures. PMID- 26160729 TI - Associations between dynamics of the blood glucose level after hypoglycemia and intensive care unit mortality: a retrospective multicenter study. PMID- 26160727 TI - Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric, prospective, observational study. AB - OBJECTIVE: To describe current use and diagnostic and therapeutic impacts of point-of-care ultrasound (POCUS) in the intensive care unit (ICU). BACKGROUND: POCUS is of growing importance in the ICU. Several guidelines recommend its use for procedural guidance and diagnostic assessment. Nevertheless, its current use and clinical impact remain unknown. METHODS: Prospective multicentric study in 142 ICUs in France, Belgium, and Switzerland. All the POCUS procedures performed during a 24-h period were prospectively analyzed. Data regarding patient condition and the POCUS procedures were collected. Factors associated with diagnostic and therapeutic impacts were identified. RESULTS: Among 1954 patients hospitalized during the study period, 1073 (55%) POCUS/day were performed in 709 (36%) patients. POCUS served for diagnostic assessment in 932 (87%) cases and procedural guidance in 141 (13%) cases. Transthoracic echocardiography, lung ultrasound, and transcranial Doppler accounted for 51, 17, and 16% of procedures, respectively. Diagnostic and therapeutic impacts of diagnostic POCUS examinations were 84 and 69%, respectively. Ultrasound guidance was used in 54 and 15% of cases for central venous line and arterial catheter placement, respectively. Hemodynamic instability, emergency conditions, transthoracic echocardiography, and ultrasounds performed by certified intensivists themselves were independent factors affecting diagnostic or therapeutic impacts. CONCLUSIONS: With regard to guidelines, POCUS utilization for procedural guidance remains insufficient. In contrast, POCUS for diagnostic assessment is of extensive use. Its impact on both diagnosis and treatment of ICU patients seems critical. This study identified factors associated with an improved clinical value of POCUS. PMID- 26160730 TI - Corticosteroids for paediatric ARDS: unjustified-even unjustifiable? PMID- 26160732 TI - Chancellor is attacked for proposed four year pay freeze. PMID- 26160731 TI - Unraveling the myriad contributors to persistent diminished exercise capacity after critical illness. PMID- 26160733 TI - Staudinger Vilarassa reaction: A powerful tool for surface modification and superhydrophobic properties. AB - Here we report for the time, the use of Staudinger-Vilarrasa reaction for fast surface functionalization. Using poly(3,4-ethylenedioxythiophene) nanofibrous surfaces bearing azido groups, this reaction allows for the functionalization of surfaces with amide linker in just 3 h. The functionalization by long alkyl chains induces the formation of highly hydrophobic surfaces while the surface structures are preserved. This reaction can be a key pathway for fast surface modification for a large range of applications such as in cell or bacterial adhesion, for example. PMID- 26160734 TI - Adsorption of odorous sulfur compounds onto activated carbons modified by gamma irradiation. AB - A commercial activated carbon (AC) was modified by gamma irradiation and was tested as adsorbent for the removal of ethyl mercaptan, dimethyl disulfide and dimethyl disulfide in wet conditions. Modifications were carried out under five different conditions: irradiation in absence of water, in presence of ultrapure water, in ultrapure water at pH=1.0 and 1000 mg L(-1) Cl(-), in ultrapure water at pH=7.5 and 1000 mg L(-1) Br(-), and in ultrapure water at pH=12.5 and 1000 mg L(-1) NO3(-). The chemical properties of each AC were characterized by elemental analysis, temperature programmed desorption and X-ray photoelectron spectroscopy. Outcomes show that a large number of oxygen functional groups were incorporated in the AC surface by gamma irradiation, especially in the AC irradiated in the presence of ultrapure water. The dynamic adsorption test results reveal that the incorporation of oxygen functional groups did not enhance the adsorption capacities for dimethyl sulfide and dimethyl disulfide. A significant improvement in the ethyl mercaptan adsorption capacity was correlated with the incorporation of phenolic groups in the AC surface. Moreover, diethyl disulfide was detected as by-product of ethyl mercaptan oxidation process under wet conditions and its formation depended on the chemical properties of ACs. PMID- 26160735 TI - Polystyrene colloidal crystals: Interface controlled thermal conductivity in an open-porous mesoparticle superstructure. AB - Colloidal crystals typically consist of sub-micron sized monodisperse particles, which are densely packed on a face centered cubic lattice. While many properties of this material class have been studied over the past decades, little is known about their thermal transport properties. The high amount of interfaces and their small interparticle contact area should result in efficient thermal insulation. Using laser flash analysis we report for the first time on the temperature dependent thermal conductivity of a freestanding 366 nm polystyrene (PS) colloidal crystal. Macroscopic monoliths of these samples were fabricated by colloidal self-assembly. We demonstrate a very low thermal conductivity kappa of 51 mW K(-1) m(-1) (kappa of bulk PS~140 mW K(-1) m(-1)). Remarkably, this low thermal conductivity is reached at a comparatively high density of 750 kg m(-3). It can be further increased by almost 300% upon film formation and loss of the colloidal mesostructure. Additionally, this open porous structure is largely independent of the surrounding atmosphere. This can be rationalized by the small size (~100 nm) of the pores present within this colloidal crystal. PMID- 26160737 TI - Short-time dynamics of pH-dependent conformation and substrate binding in the active site of beta-glucosidases: A computational study. AB - The complete degradation of cellulose to glucose is essential to carbon turnover in terrestrial ecosystems and to engineered biofuel production. A rate-limiting step in this pathway is catalyzed by beta-glucosidase (BG) enzymes, which convert cellulobiose into two glucose molecules. The activity of these enzymes has been shown to vary with solution pH. However, it is not well understood how pH influences the enzyme conformation required for catalytic action on the substrate. A structural understanding of this pH effect is important for predicting shifts in BG activity in bioreactors and environmental matrices, in addition to informing targeted protein engineering. Here we applied molecular dynamics simulations to explore conformational and substrate binding dynamics in two well-characterized BGs of bacterial (Clostridium cellulovorans) and fungal (Trichoderma reesei) origins as a function of pH. The enzymes were simulated in an explicit solvated environment, with NaCl as electrolytes, at their prominent ionization states obtained at pH 5, 6, 7, and 7.5. Our findings indicated that pH dependent changes in the ionization states of non-catalytic residues localized outside of the immediate active site led to pH-dependent disruption of the active site conformation. This disruption interferes with favorable H-bonding interactions with catalytic residues required to initiate catalysis on the substrate. We also identified specific non-catalytic residues that are involved in stabilizing the substrate at the optimal pH for enzyme activity. The simulations further revealed the dynamics of water-bridging interactions both outside and inside the substrate binding cleft during structural changes in the enzyme-substrate complex. These findings provide new structural insights into the pH-dependent substrate binding specificity in BGs. PMID- 26160736 TI - Evolutionary decay and the prospects for long-term disease intervention using engineered insect vectors. AB - After a long history of applying the sterile insect technique to suppress populations of disease vectors and agricultural pests, there is growing interest in using genetic engineering both to improve old methods and to enable new methods. The two goals of interventions are to suppress populations, possibly eradicating a species altogether, or to abolish the vector's competence to transmit a parasite. New methods enabled by genetic engineering include the use of selfish genes toward either goal as well as a variety of killer-rescue systems that could be used for vector competence reduction. This article reviews old and new methods with an emphasis on the potential for evolution of resistance to these strategies. Established methods of population suppression did not obviously face a problem from resistance evolution, but newer technologies might. Resistance to these newer interventions will often be mechanism-specific, and while it is too early to know where resistance evolution will become a problem, it is at least possible to propose properties of interventions that will be more or less effective in blocking resistance evolution. PMID- 26160738 TI - Concentrations and loads of suspended sediment and trace element pollutants in a small semi-arid urban tributary, San Francisco Bay, California. AB - Water-quality policy documents throughout the world often identify urban stormwater as a large and controllable impact to sensitive ecosystems, yet there is often limited data to characterize concentrations and loads especially for rare and more difficult to quantify pollutants. In response, concentrations of suspended sediments and silver, mercury and selenium including speciation, and other trace elements were measured in dry and wet weather stormwater flow from a 100% urban watershed near San Francisco. Suspended sediment concentrations ranged between 1.4 and 2700 mg/L and varied with storm intensity. Turbidity was shown to correlate strongly with suspended sediments and most trace elements and was used as a surrogate with regression to estimate concentrations during unsampled periods and to compute loads. Mean suspended sediment yield was 31.5 t/km(2)/year. Total mercury ranged between 1.4 and 150 ng/L and was, on average, 92% particulate, 0.9% methylated, and 1.2% acid labile. Total mercury yield averaged 5.7 MUg/m(2)/year. Total selenium ranged between non-detect and 2.9 MUg/L and, on average, the total load (0.027 MUg/m(2)/year) was 61% transported in dissolved phase. Selenate (Se(VI)) was the dominant species. Silver concentrations ranged between non-detect and 0.11 MUg/L. Concentrations and loads of other trace elements were also highly variable and were generally similar to other urban systems with the exceptions of Ag and As (seldom reported) and Cr and Zn which exhibited concentrations and loads in the upper range of those reported elsewhere. Consistent with the semi-arid climatic setting, >95% of suspended sediment, 94% of total Hg, and 85-95 % of all other trace element loads were transported during storm flows with the exception of selenium which showed an inverse relationship between concentration and flow. Treatment of loads is made more challenging in arid climate settings due to low proportions of annual loads and greater dissolved phase during low flow conditions. This dataset fills an important local data gap for highly urban watersheds of San Francisco Bay. The field and interpretative methods, the uniqueness of the analyte list, and resulting information have general applicability for managing pollutant concentrations and loads in urban watersheds in other parts of the world and may have particularly useful application in more arid climates. PMID- 26160739 TI - Spatial variation of eco-physiological parameters in the lichen Pseudevernia furfuracea transplanted in an area surrounding a cement plant (S Italy). AB - Thalli of the lichen Pseudevernia furfuracea were transplanted for 3 months (November 2010-January 2011) at 61 monitoring sites around a cement plant near Castrovillari (Calabria, southern Italy). NH3, NO x and SO2 concentrations were monitored monthly in a subarea of 10 sites (SA10) where the cement plant was located. At the end of the exposure period, the integrity of cell membranes; membrane lipid peroxidation (thiobarbituric acid reactive substances, TBARS level); vitality (cell respiration); chlorophyll a; chlorophyll b; carotenoids; phaeophytization quotient; photosynthetic efficiency and thalli concentrations of Al, Ca, Mg, V and Fe were measured. NO x concentrations correlated with the site distance from the cement plant while NH3 concentrations correlated with lichen vitality within SA10. For the monitoring area as a whole, only Fe and Mg concentrations correlated with membrane lipid peroxidation, while TBARS levels showed a significant increase and chlorophyll a, chlorophyll b and carotenoids a significant decrease with respect to the lichen origin area. Multivariate analysis (detrended correspondence analysis, cluster analysis and multi-response permutation procedure) of the eco-physiological parameters * monitoring sites data set resulted in four clusters termed C1, C2, C3 and C4. The eco physiological parameters were compared among the four clusters and lichen origin area by one-way ANOVA. An index of environmental favourableness (IEF) to lichens was calculated to evaluate the spatial recovery of impaired values of TBARS, chlorophyll a, chlorophyll b, xanthophylls + carotenoids and phaeophytization quotient. The results indicate that there is no clear spatial trend in mycobiont impairment even though the IEF values suggest a higher number of sites with low levels of membrane lipid peroxidation in the 2--3-km distance band from the cement plant (the outermost) than in the two other distance bands (0-1 and 1-2 km). The photobiont seems to be damaged mainly in the inner distance band of the study area as suggested by the gradual but significant recovery trend of pigment levels and phaeophytization quotient from the inner distance band to the outer one (as shown by the IEF values). Conversion of chlorophyll to phaeophytin probably is not the only process affecting pigment levels. PMID- 26160740 TI - Methylation index as means of quantification of the compliance of sedimentary mercury to be methylated. AB - Methylmercury (MeHg) is the most bioavailable and toxic mercury species in the marine environment. MeHg concentration levels, methylation rates leading to MeHg formation, and methylation index (MI) are all used to assess the compliance of mercury to be methylated in the marine sedimentary environment. This paper reports on the works conducted on the MI upgrade. This paper proposes a new formula for calculating MI. Apart from labile mercury(II) and organic matter, it includes redox potential and abundance of sulfur-reducing bacteria (SRB), both essential factors for MeHg generation. The obtained MI is validated against actual sedimentary MeHg concentrations proving the potential usefulness of MI as a factor characterizing status of sedimentary environment regarding possible occurrence of MeHg. Moreover, values of the methylation index in particular regions show that MI values correspond well to environmental conditions in those areas. The values calculated correlate well with MeHg concentrations; however, the correlation coefficients vary between different regions. This has been attributed to the lack of empirical coefficients. Thus, MI could be used as a characteristic of the sedimentary environment indicating the potential presence of MeHg. It could also be used in methylation rate modeling, provided that empirical constants are applied to improve model performance. PMID- 26160741 TI - Solid-phase extraction of iridium from soil and water samples by using activated carbon cloth prior to its spectrophotometric determination. AB - A solid-phase extraction method for separation and preconcentration of Ir(IV) ion by using activated carbon cloth (ACC) has been presented. Ir(IV) as their 1-(2 pyridylazo) 2-naphtol (PAN) chelate was adsorbed on ACC at pH 2.0 and was eluted from ACC with acidic dimethylformamide (DMF). The Ir(IV) concentration was determined at 536 nm as Ir(IV)-PAN complex by using UV-vis spectrophotometer. The analytical parameters including pH, sample and eluent flow rates, amount of PAN, eluent type, concentration, and sample volume were optimized. The effects of foreign ions on the recoveries of iridium were also investigated. The preconcentration factor was calculated as 60. The limit of detection (LOD) and the limit of quantification (LOQ) of the method were found as 0.039 and 0.129 MUg L(-1), respectively. The method was applied to soil and water samples for iridium determination. PMID- 26160742 TI - Neighbourhood fluorosis in people residing in the vicinity of superphosphate fertilizer plants near Udaipur city of Rajasthan (India). AB - Chronic industrial fluoride toxicosis in the forms of dental, skeletal and non skeletal fluorosis was investigated in 162 villagers (94 males and 78 females) above 15 years of age living in the vicinity of superphosphate fertilizer plants located approximately 12 km south of Udaipur city of Rajasthan, India. Out of these villagers, 90 (55.5%) and 29 (18.0%) were found to be afflicted with mild to severe dental and skeletal fluorosis, respectively. Dental fluorosis characterized with light to deep-brownish bilaterally striated horizontal lines, pits or patches and fine dots or granules was noted on incisor teeth of villagers. Irregular wearing, excessive corrosions (abrasions), dark-brownish pigmentation of exposed cementum and dentine material, diastem as between teeth, pronounced loss of tooth supporting bone with recession and bulging of gingiva (gum) were also present in subjects of older age group (>55 years). Among 29 (18.0%) individuals, mild to moderate manifestations of skeletal fluorosis such as crippling, kyphosis, invalidism and genu-varum syndrome were found. In these fluorotic subjects pain/rigidity in major joints viz. neck, back, hip, knee and shoulder was also found. None of the fluorotic subjects showed evidence of genu valgum syndrome. Other signs of chronic industrial fluoride intoxication in soft tissues (non-skeletal fluorosis) included colic, intermittent diarrhoea or constipation, bloating, polyuria and polydipsia. These findings indicate that surrounding environment of superphosphate fertilizer plants is contaminated with fluoride emission, which in turn is causing diverse ill health effects in humans which are discussed. PMID- 26160743 TI - The Decline of Pertussis-Specific Antibodies After Tetanus, Diphtheria, and Acellular Pertussis Immunization in Late Pregnancy. AB - We prospectively measured pertussis-specific antibodies 9-15 months after delivery in women immunized with tetanus, diphtheria, and acellular pertussis (Tdap) after the 20th week of their recent pregnancy. The Tdap-immunized women (n = 38) exhibited a decline in geometric mean concentrations between their peripartum and follow-up levels for immunoglobulin G to pertussis toxin (21.48 [95% confidence interval, 12.51-36.89] vs 11.72 [7.09-19.37] IU/mL];); filamentous hemagglutinin (185.95 [157.93-218.94] vs 140.33 IU/mL [113.46-173.57] IU/mL); and pertactin (171.52 [120.73-243.67] vs 83.74 [60.58-115.75] IU/mL) (all P < .001). For women immunized with Tdap during late pregnancy, pertussis specific immunoglobulin G levels decreased significantly 9-15 months after delivery. PMID- 26160744 TI - Outcomes and Susceptibility to Neuraminidase Inhibitors in Individuals Infected With Different Influenza B Lineages: The Influenza Resistance Information Study. AB - BACKGROUND: Little is known about how influenza infections caused by B/Victoria and B/Yamagata virus lineages compare with respect to disease course and susceptibility to antiviral therapy. METHODS: Data from patients with influenza B infections from the first 5 years (2009-2013) of the prospective Influenza Resistance Information Study (IRIS, NCT00884117) were evaluated. Cultured viruses were phenotypically tested for neuraminidase inhibitor (NAI) sensitivity, and sequenced to determine virus lineage (B/Victoria or B/Yamagata). Differences in clinical outcomes (viral clearance and symptom resolution) between virus lineages were assessed using Kaplan-Meier analysis. RESULTS: In all, 914 patients were positive for influenza B by reverse transcriptase polymerase chain reaction ( RT PCR: B/Victoria, 586; B/Yamagata, 289; not subtyped, 39); 474 were treated with antivirals. No phenotypic resistance to oseltamivir or zanamivir was found in B/Victoria or B/Yamagata viruses. Of 15 predefined resistance mutations, 2 were detected by neuraminidase sequencing: I221T had reduced sensitivity to oseltamivir, and I221V was sensitive to NAI inhibition. No consistent differences between virus lineages in times to viral clearance or to symptom or fever resolution were found in adults and adolescents or in children. CONCLUSIONS: Influenza B virus lineage had no notable effect on disease outcomes or antiviral susceptibility in this population. PMID- 26160745 TI - Multidrug-Resistance Transporter AbcA Secretes Staphylococcus aureus Cytolytic Toxins. AB - Phenol-soluble modulins (PSMs) are Staphylococcus aureus cytolytic toxins that lyse erythrocytes and neutrophils and have important functions in the S. aureus infectious process. The molecular mechanisms of PSM secretion, however, are not well understood. Here we report that knockout of the multidrug-resistance ABC transporter AbcA, which contributes to S. aureus resistance against antibiotics and chemicals, diminished the secreted amount of PSM, leading to the accumulation of PSM in the intracellular fraction. The amount of PSM in the culture supernatants of the abcA knockout mutants was restored by introduction of the wild-type abcA gene, whereas it was not completely restored by introduction of mutant abcA genes encoding AbcA mutant proteins carrying amino acid substitutions in the adenosine triphosphate binding motifs. The abcA knockout mutant exhibited attenuated virulence in a mouse systemic infection model. These findings suggest that the multidrug resistance transporter AbcA secretes PSMs and contributes to S. aureus virulence. PMID- 26160746 TI - Genotoxicity assessment of pesticides on terrestrial snail embryos by analysis of random amplified polymorphic DNA profiles. AB - The study explores the relevance of coupling Random Amplified Polymorphic DNA (RAPD) and a High-Resolution capillary electrophoresis System (HRS) method for assessing the genotoxic potential of the wide variety commercial formulations of pesticides. Using this technique, the genotoxic potential of a glyphosate-based herbicide (Roundup Flash((r)) (RU)) and two fungicide formulations based on tebuconazole and copper (Corail((r)) and Bordeaux mixture (BM), respectively) was evaluated on terrestrial snail embryos. Clutches of Cantareus aspersus were exposed during their entire embryonic development to a range of concentration around the EC50 values (based on hatching success) for each compound tested. Three primers were used for the RAPD amplifications of pesticides samples. RAPD HRS revealed concentration-dependent modifications in profiles generated with the three primers in RU((r))-exposed embryos from 30 mg/L glyphosate. For Corail((r)) exposed embryos, only two of the three primers were able to show alterations in profiles from 0.05 mg/L tebuconazole. For BM-exposed embryos, no signs of genotoxicity were observed. All changes observed in amplification profiles have been detected at concentrations lower than the recommended doses for vineyard field applications. Our study demonstrates the efficiency of coupling RAPD and HRS to efficiently screen the effect of pesticide formulations on DNA. PMID- 26160747 TI - Gastroprotective effect of Cymbopogon citratus infusion on acute ethanol-induced gastric lesions in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Treatment of gastric ulcers with medicinal plants is quite common in traditional medicine worldwide. Cymbopogon citratus (DC) Stapf. leaves infusion has been used in folk medicine of many tropical and subtropical regions to treat gastric disturbances. The aim of this study was to assess the potential gastroprotective activity of an essential oil-free infusion from C. citratus leaves in acute gastric lesions induced by ethanol in rat. MATERIALS AND METHODS: The study was performed on adult male Wistar rats (234.0+/ 22.7g) fasted for 24h but with free access to water. The extract was given orally before (prevention) or after (treatment) intragastric administration of absolute ethanol. Effects of dose (28 or 56mg/kg of body weight) and time of contact of the extract with gastric mucosa (1 or 2h) were also assessed. Animals were sacrificed, being the stomachs removed and the lesions were assessed by macroscopic observation and histopathology. RESULTS: C. citratus extract, given orally before or after ethanol, significantly (P<0.01) reduced gastric mucosal injury compared with control group (vehicle+ethanol). The effect does not appear to be dose-dependent. Results also suggested that the extract is more effective when the time of contact with gastric mucosa increases. CONCLUSIONS: The results of this assay confirm the gastroprotective activity of C. citratus extract on experimental gastric lesions induced by ethanol, contributing for the pharmacological validation of its traditional use. PMID- 26160748 TI - Analgesic effects and possible mechanisms of iridoid glycosides from Lamiophlomis rotata (Benth.) Kudo in rats with spared nerve injury. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lamiophlomis rotata (Benth.) Kudo (L. rotata) is a medical plant that has been traditionally used for centuries for the treatment of pain, such as bone and muscle pain, joint pain and dysmenorrhea. Although iridoid glycosides of L. rotata (IGLR) are the major active components of it according to reports, it still remains poorly understood about the molecular mechanisms underlying analgesic effects of IGLR. The aim of the present study was to investigate the analgesic effect of IGLR on a spared nerve injury (SNI) model of neuropathic pain. MATERIALS AND METHODS: The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. Then SNI rats were treated with IGLR for 14 days, using normal saline as the negative control. The paw withdrawal mechanical threshold (PMWT) in response to mechanical stimulation was measured by von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 9, 11, 13 and 14 after operation, respectively. After 14 days, the levels of nitric oxide (NO), nitric oxide synthase (NOS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-10 (IL-10) and cyclic guanosine monophosphate (cGMP) in the spinal dorsal horn were measured by the corresponding kits, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKGI) of spinal cord were analyzed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of N-methyl-D-aspartate receptor (NMDAR) and protein kinase C (PKCgamma) of the spinal dorsal horn was performed by Western blot. Before all the experiments, motor coordination performance and locomotor activity had been tested. RESULTS: Our results showed that remarkable mechanical allodynia was observed on day 1 after operation in the SNI model, which was accompanied by a decrease in PMWT. Treatment with IGLR (200, 400, 800mg/kg) significantly alleviated SNI-induced mechanical allodynia, markedly decreased the levels of NO, NOS, TNF-alpha, IL-1beta and cGMP, and increased the level of IL-10. Meanwhile, IGLR (200, 400, 800mg/kg) also inhibited the protein expression of NMDAR, PKCgamma and the mRNA expression of iNOS and PKGIota in the spinal cord. In addition, gavage with the IGLR aqueous extract (800mg/kg) did not signifiantly alter motor coordination or locomotor activity. CONCLUSIONS: These results indicated IGLR could produce an anti-neuropathic pain effect that might partly be related to the inhibition of the NO/cGMP/PKG and NMDAR/PKC pathways and the level of TNF-alpha, IL-1beta as well as to the increase of the level of IL-10 in spinal cord. PMID- 26160749 TI - Science and film-making. AB - The essay reviews the literature, mostly historical, on the relationship between science and film-making, with a focus on the science documentary. It then discusses the circumstances of the emergence of the wildlife making-of documentary genre. The thesis examined here is that since the early days of cinema, film-making has evolved from being subordinate to science, to being an equal partner in the production of knowledge, controlled by non-scientists. PMID- 26160750 TI - 8th International Conference on Inhibitors of Protein Kinases (IPK '2014). PMID- 26160751 TI - Structural and biophysical analysis of sero-specific immune responses using epitope grafted Dengue ED3 mutants. AB - Dengue fever is a re-emerging tropical disease and its severe form is caused by cross-reactivity between its four serotypes (DEN1, DEN2, DEN3 and DEN4). The third domain of the viral envelope protein (ED3) contains the two major putative epitopes and is a highly suitable model protein for examining the molecular determinants of a virus' sero-specificity. Here we examine d the sero-specificity and cross-reactivity of the immune response against DEN3 and DEN4 ED3 using six epitope grafted ED3 variants where the surface-exposed epitope residues from DEN3 ED3 were switched to those of DEN4 ED3 and vice versa. We prepared anti-DEN3 and anti-DEN4 ED3 serum by immunizing Swiss albino mice and measured their reactivities against all six grafted mutants. As expected, both sera exhibited strong reactivity against its own serotype's ED3, and little cross-reactivity against their counterpart serotype's ED3s. E2 played a major role in the sero specificity of anti-DEN3 serum, whereas E1 was important for DEN4 ED3's sero specificity. Next, the reactivity patterns corroborated our working hypothesis that sero-specificity could be transferred by grafting the surface exposed epitope residues from one serotype to the other. To analyze the above results from a structural viewpoint, we determined the crystal structure of a DEN4 ED3 variant, where E2 was grafted from DEN3 ED3, at 2.78A resolution and modeled the structures of the five remaining grafted variants by assuming that the overall backbone remained unchanged. The examination of the electrostatic and molecular surfaces of the variants suggested some further rationale for the sero specificity of the immune responses. PMID- 26160752 TI - Changing risk of environmental Campylobacter exposure with emerging poultry production systems in Ethiopia. AB - Campylobacter is a leading cause of diarrhoea, and its presence in chickens is a significant risk for zoonotic infection. Poultry production is becoming increasingly intensive in Ethiopia and is incorporating more high-producing breeds into traditionally managed smallholdings, especially in peri-urban areas. This cross-sectional study sampled 219 household environments in one peri-urban and two rural areas of Ethiopia, and an additional 20 semi-intensive farms in the peri-urban district. Campylobacter was detected by polymerase chain reaction (PCR)-specific assays in 44 samples; 16 of which could be identified as C. jejuni. Flocks in the peri-urban area were at significantly greater odds of detection, including those which only kept indigenous birds under a scavenging system. It was also noted that scavenging flocks of exotic high-production birds (Rhode Island Red) were at slightly greater risk, perhaps as exotic birds are under more stress when kept under traditional management systems. We suggest that changes to the system of chicken production may alter the ecology and epidemiology of Campylobacter in the environment, chickens and people, which may drive emergence of new epidemiological patterns of disease. Further research is needed to determine the extent to which the current management intensification and the distribution programmes of exotic and/or improved indigenous birds may alter Campylobacter epidemiology, ecology and public health risk, before their widespread adoption. PMID- 26160753 TI - Exclusion probabilities and likelihood ratios with applications to mixtures. AB - The statistical evidence obtained from mixed DNA profiles can be summarised in several ways in forensic casework including the likelihood ratio (LR) and the Random Man Not Excluded (RMNE) probability. The literature has seen a discussion of the advantages and disadvantages of likelihood ratios and exclusion probabilities, and part of our aim is to bring some clarification to this debate. In a previous paper, we proved that there is a general mathematical relationship between these statistics: RMNE can be expressed as a certain average of the LR, implying that the expected value of the LR, when applied to an actual contributor to the mixture, is at least equal to the inverse of the RMNE. While the mentioned paper presented applications for kinship problems, the current paper demonstrates the relevance for mixture cases, and for this purpose, we prove some new general properties. We also demonstrate how to use the distribution of the likelihood ratio for donors of a mixture, to obtain estimates for exceedance probabilities of the LR for non-donors, of which the RMNE is a special case corresponding to L R>0. In order to derive these results, we need to view the likelihood ratio as a random variable. In this paper, we describe how such a randomization can be achieved. The RMNE is usually invoked only for mixtures without dropout. In mixtures, artefacts like dropout and drop-in are commonly encountered and we address this situation too, illustrating our results with a basic but widely implemented model, a so-called binary model. The precise definitions, modelling and interpretation of the required concepts of dropout and drop-in are not entirely obvious, and we attempt to clarify them here in a general likelihood framework for a binary model. PMID- 26160754 TI - Detection of the ethanol consumption markers ethyl glucuronide and ethyl sulfate in urine samples from inmates of two German prisons. AB - INTRODUCTION: Abstinence from ethanol is necessary in various situations. Among these are jail terms. Nevertheless, it is a matter of fact that ethanol is illegally produced and ingested in prisons. So far, data regarding drug prevalence in jail have mainly been collected by questionnaires. To get an objective database for the prevalence of ethanol consumption in jail, a cross sectional study was performed. METHODS: Inmates of two German prisons (Offenburg and Freiburg) were asked to give a urine sample at an unknown and random point of time. Participation was voluntary and did lead to neither negative consequences nor benefits. All samples were anonymized. Using the consumption markers ethyl glucuronide (EtG) and ethyl sulfate (EtS), the urine samples were tested for previous ethanol consumption. Analyses were performed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: In total 676 male inmates participated in this study. The participation rate was 70-75% of all permanent inmates in Offenburg and 30.6% in Freiburg. Ten of the 555 (1.8%) samples from Offenburg and 1 of the 121 (0.8%) samples from Freiburg were positive for ethanol consumption markers with concentrations ranging from trace amounts to 1400 ng/mL for EtG and up to 510 ng/mL for EtS, respectively. CONCLUSIONS: The number of participants in this study was rather high, so that the results represent a good cross section, at least for Offenburg, the jail with the higher number of positive samples. PMID- 26160755 TI - A synthetic tRNA for EF-Tu mediated selenocysteine incorporation in vivo and in vitro. AB - Incorporation of selenocysteine (Sec) in bacteria requires a UGA codon that is reassigned to Sec by the Sec-specific elongation factor SelB and a conserved mRNA motif (SECIS element). These requirements severely restrict the engineering of selenoproteins. Earlier, a synthetic tRNASec was reported that allowed canonical Sec incorporation by EF-Tu; however, serine misincorporation limited its scope. We report a superior tRNASec variant (tRNAUTuX) that facilitates EF-Tu dependent stoichiometric Sec insertion in response to UAG both in vivo in Escherichia coli and in vitro in a cellfree protein synthesis system. We also demonstrate recoding of several sense codons in a SelB supplemented cell-free system. These advances in Sec incorporation will aid rational design and directed evolution of selenoproteins. PMID- 26160756 TI - miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma. AB - This study aimed to identify a single miRNA or miR (microRNA) which regulates the three insulin-like growth factor-2-mRNA-binding proteins (IGF2BP1, 2 and 3). Bioinformatics predicted miR-1275 to simultaneously target the three IGF2BPs, and screening revealed miR-1275 to be underexpressed in hepatocellular carcinoma (HCC) tissues. Transfection of HuH-7 cells with miR-1275 suppressed IGF2BPs expression and all three IGF2BPs were confirmed as targets of miR-1275. Ectopic expression of miR-1275 and knockdown of IGF2BPs inhibited malignant cell behaviors, and also reduced IGF1R protein and mRNA. Finally IGF1R was validated as a direct target of miR-1275. These findings indicate that the tumor-suppressor miR-1275 can control HCC tumor growth partially through simultaneously regulating the oncogenic IGF2BPs and IGF1R. PMID- 26160757 TI - Antitumor activity in advanced cancer patients with thymic malignancies enrolled in early clinical drug development programs (Phase I trials) at Gustave Roussy. AB - OBJECTIVES: Thymic epithelial neoplasms (TENs) represent a rare entity with poor prognosis and limited systemic treatment options. The aim of this study was to assess the clinical benefit, the efficacy and toxicities of agents for patients with TEN enrolled in Phase I trials. MATERIALS AND METHODS: We reviewed retrospectively patients with advanced TEN enrolled in Phase I trials at Gustave Roussy (DITEP) between 1994 and 2012. Efficacy was assessed using RECIST version 1.1. RESULTS: Twenty-two treated patients were enrolled (15 with thymic carcinoma, 7 with thymoma). The median number of prior systemic therapies was 2 (0-8). The median age was 50 years (range 23-72), and 4 females were treated. Treatments received encompassed mTOR inhibitor (mTORi) in 4 of patients, antiangiogenic agents (AA) in 11 patients, and other targeted therapies in 7 patients. 18% had grade 3-4 toxicity, 85% all grade toxicity and no toxic death was reported. One patient experienced a complete response (CR) and 3 a partial response (PR); 16 patients had stable disease (median 6.6 months; range 1.0-30.7) and 2 had a progressive disease. The median overall survival was 54.5 months (95% CI 25-75.50). The median progression free survival (PFS) was 6.6 months (95% CI 1.35-11.59). Median PFS was 11.6 months for mTORi, 6.9 for AA, and 6.6 for other targeted therapies. CONCLUSION: Phase I trials appear as a sound therapeutic option in TENs pts progressing after standard treatments. Use of AA and mTORi seem to yield a good clinical response and warrant further investigation. PMID- 26160758 TI - Keratinized strap cells: a rare cytological atypia resembles Anitschkow cells, in human oral neoplasm. AB - BACKGROUND: Cytopathology of human oral squamous cell carcinoma reveals cytological pleomorphism. In this investigation, cytometry was used in an attempt to analyse the importance of the rare occurrence of keratinized strap cells in the buccal mucosa of human oral neoplasms. PATIENTS AND METHODS: A case-control study was undertaken in which exfoliated cytosmears were collected, by scraping, from 136 clinically diagnosed oral cancer patients. Wet fixed cytosmears were stained by use of Papanicolaou's staining procedure and counter-stained with Giemsa's solution. One thousand cells were screened, and keratinized strap (Anitschkow) cells (KSC-A) and other cytological atypias were counted. Cytomorphometry was performed by use of a computer-assisted microscope camera. The findings were analysed statistically and interpreted in respect of age group, oral site, and sex. RESULTS: Transformation of an angulated and polygonal normal oral squamous cell into a keratinized narrow strip or ribbon-like flat projection results in what is called a keratinized strap cell (KSC). Nuclear pleomorphism in keratinized strap cells was observed to be narrow spindle, rod, and bar-shaped and to resemble Anitschkow cells. From the nature of the staining, the structural peculiarity, and the resemblance to Anitschkow cells, KSC, a rarely observed oral cytological atypia, were renamed as keratinized strap (Anitschkow) (KSC-A) cells. Cytometrically, the nuclear-to-cytoplasmic (N/C) ratio for KSC-A was calculated to be 1:11.2 for males and 1:11.3 for females; these are more than those for the normal counterparts. CONCLUSION: Rare occurrence, cellular keratinization, nuclear pleomorphism, hyperchromasia, and increased N/C ratios for KSC-A in oral carcinoma, for both sexes, indicate a state of malignancy; this finding is, thus, of practical value for early detection and diagnosis of oral squamous cell carcinoma patients. PMID- 26160759 TI - Phosphine-catalyzed [4+1] annulation of 2-tosylaminochalcones with allenoates: synthesis of trans-2,3-disubstitued indolines. AB - Phosphine-catalyzed [4+1] annulation of 2-tosylaminochalcones with allenoates has been achieved, giving trans-2,3-disubstitued indolines as major diastereoisomers in moderate to good yields. PMID- 26160760 TI - Are titanium-on-titanium TiAl6V4 modular necks safe in total hip arthroplasty for non-overweight patients? Results of a prospective series at a minimum follow-up of 7 years. AB - Using extramedullar modularity in total hip arthroplasty has been proposed as an option to optimize the restoration of hip biomechanics. To avoid the problems that were observed with cobalt-chrome modular neck, titanium modular necks have been developed. The goals of our study were to evaluate the safety of titanium-on titanium TiAl6V4 modular neck system. Hundred patients with a mean age of 69.6 +/ 10.6 (42-86 years) and mean BMI of 25.07 +/- 4.86 (17-38 kg/m(2)) suffering from primary or secondary arthritis of the hip were prospectively included. At a minimum of 7 years, no fracture of the modular neck was observed. No patient required a revision. No sign of loosening was found in the radiological analysis. Our study shows that titanium-on-titanium TiAl6V4 modular neck system can safely be used with good midterm clinical and radiological results for non-overweight patients. These results should be confirmed at longer follow-up. PMID- 26160761 TI - PPARbeta/delta Agonist Provides Neuroprotection by Suppression of IRE1alpha Caspase-12-Mediated Endoplasmic Reticulum Stress Pathway in the Rotenone Rat Model of Parkinson's Disease. AB - Two recent studies demonstrated that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) agonists exerted neuroprotective effects in mouse model of Parkinson's disease (PD). However, the underlying mechanisms remain unknown. Endoplasmic reticulum (ER) stress plays a major role in rotenone-induced dopaminergic neuronal degeneration. In the present study, we explored whether GW501516, a selective and high-affinity PPARbeta/delta agonist, could protect the dopaminergic neurons against degeneration and improve PD behavior via suppressing the ER stress in the rotenone rat model of PD. GW501516 was administered intracerebroventricular infusion. Catalepsy and open field tests were used to test catalepsy and locomotor activities. The levels of dopamine and its metabolites were determined using high-performance liquid chromatography. Western blot and immunohistochemistry analysis were performed to assess dopaminergic neuronal degeneration. Quantitative real-time RT-PCR and Western blot analysis were executed to detect ER stress. TUNEL and immunohistochemistry assays were used to detect ER stress-mediated apoptosis. Our results showed that GW501516 ameliorated the catalepsy symptom and increased locomotor activity. Meanwhile, GW501516 partially reversed the loss of dopaminergic neurons. Moreover, GW501516 suppressed the activation of ER stress markers including inositol-requiring enzyme 1alpha (IRE1alpha) and caspase-12. Furthermore, GW501516 inhibited caspase 12-mediated neuronal apoptosis. These findings suggest that GW501516 conferred neuroprotection of not only biochemical and pathological attenuation but also behavioral improvement in the rotenone rat model of PD. More importantly, we demonstrated for the first time that suppressing IRE1alpha-caspase-12-mediated ER stress pathway may represent one potential mechanism underlying the neuroprotective effects of PPARbeta/delta agonist in the rotenone rat model of PD. PMID- 26160762 TI - Bis(propyl)-cognitin Prevents beta-amyloid-induced Memory Deficits as Well as Synaptic Formation and Plasticity Impairments via the Activation of PI3-K Pathway. AB - Bis(propyl)-cognitin (B3C), derived from tacrine linked with three methylene ( CH2-) groups, is a dimerized molecule interacting multiple targets. During the past several years, it has been reported as a promising therapeutic drug for Alzheimer's disease (AD) and other neurodegenerative disorders. However, the therapeutic mechanism of B3C for AD needs further demonstration. Based on a combination of behavioral tests, electrophysiological technique, immunocytochemistry, and live cell imaging, we studied the effects and the underlying mechanism of B3C on the impairments of cognitive function, synapse formation, and synaptic plasticity induced by soluble amyloid-beta protein (Abeta) oligomers. Our study showed that spatial learning and memory in a Morris water maze task and recognition memory in a novel object recognition task were significantly decreased in the AD model mice created by hippocampal injection of Abeta. Chronic administration of B3C for 21 days prevented the memory impairments of the AD model mice in a dose-dependent manner. Live cell imaging study showed that 2-h pretreatment of B3C prevented the decrease in the number of filopodia and synapses induced by Abeta (0.5 MUM) in a dose-dependent manner. Besides, electrophysiological recording data showed that the inhibition of long-term potentiation (LTP) induced by Abeta1-42 oligomers in the dentate gyrus (DG) of hippocampus was prevented by B3C in a dose-dependent manner. Furthermore, we found that the neuroprotective effect of B3C against Abeta-oligomer-induced impairments of synaptic formation and plasticity could be partially blocked by a specific phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 (50 MUM). Therefore, these results indicate that B3C can prevent Abeta-oligomer-induced cognitive deficits, synaptic formation impairments, and synaptic plasticity impairments in a concentration-dependent manner. These effects of B3C are partially mediated via the PI3-K pathway. This study provides novel insights into the cellular mechanisms for the protective effects of B3C on AD. PMID- 26160764 TI - [Has the performing of imaging tests improved back pain in the elderly?]. PMID- 26160763 TI - Stump closure reinforcement with absorbable fibrin collagen sealant sponge (TachoSil) does not prevent pancreatic fistula after distal pancreatectomy: the FIABLE multicenter controlled randomized study. AB - BACKGROUND: The aim of this study is to evaluate the effectiveness of TachoSil sponge on distal pancreatectomy remnant stump in reducing the rate and severity of postoperative pancreatic fistula (POPF). METHODS: All consecutive patients requiring distal pancreatectomy were randomized in 45 centers. The principal end point was onset of "clinically relevant" POPF. Univariate and multivariate analyses were searched for predictive factors. RESULTS: Of the 270 patients randomized (134 with TachoSil; 136 without), 150 (55.6%) patients sustained a POPF [74 clinically relevant and 76 clinically silent (27.4% and 28.1%), respectively]: no statistically significant difference was found between patients sustaining clinically relevant POPF [41 (30.6%) with vs 33 (24.3%) without TachoSil (P = .276)], or overall POPF [73 (54.5%) with vs 77 (56.6%) without TachoSil, (P = .807)], but there were more clinically relevant POPF after hand sewn (32.3%) versus mechanical closure (19.8%) (P = .025) and, in case of splenic preservation, after splenic vessel ligation (15/32, 46.9%) versus vascular preservation (17/72, 23.6%) (P = .024). Hand-sewn pancreatic remnant closure (P = .023) and splenic vessel ligation in splenic preservation (P = .035) were independent predictive factors for the onset of clinically relevant POPF. CONCLUSION: TachoSil sponge reinforcement of the proximal remnant after distal pancreatectomy reduced neither the rate nor the severity of POPF. PMID- 26160765 TI - [Quality of life of patients with asthma on beclomethasone/formoterol. Cost utility analysis]. AB - AIM: To perform a cost-utility analysis on asthmatic patients on beclomethasone/formoterol fixed combination in Primary Health Care. Material and methods Non-probability sampling was used to select a group of asthmatic patients with moderate/severe persistent severity (GEMA 2009), treated with beclomethasone/formoterol fixed combination, over 18 years, had given their informed consent. The study observation period was 6 months. The variables studied were: age, sex, duration of disease, health resources used, analysis of health related quality of life by EQ-5D and SF-36, and the specific Asthma Quality of Life Questionnaire. For the qualitative variables, the frequency and percentages were calculated, and for the quantitative variables, the mean, SD and 95% CI. Chi-square, Student t-test and ANOVA were used for statistical inference. Comparisons were made with a statistical significance of 0.05. RESULTS: Of the 64 patients that completed the study, 59.4% were female. The mean age was 49 years, and mean disease duration was 93 months. For asthma control, 53% of patients had a prescription pattern of one/12h. All health related quality of life scales were modified with respect to the baseline and the differences were statistically significant. Our patients had a better health related quality of life than Spanish asthma cohort. The incremental cost utility beclomethasone/formoterol versus usual treatment option was ? 6,256/QALY. PMID- 26160766 TI - A novel technique for reducing pancreatic fistulas after pancreaticojejunostomy. AB - Risk factors for anastomotic leaks of pancreaticojejunostomy have been well described. We present a technique using indocyanine green dye (ICG) and a near infrared (NIR) capable laparoscope to assess blood supply to the transected margin of the pancreas before pancreaticojejunal anastomosis. A 39-year-old female patient underwent a laparoscopic-assisted pancreaticoduodenectomy (Whipple's procedure) for an invasive ampullary adenocarcinoma. Before construction of the pancreaticojejunal anastomosis, the viability of the margin of the remnant pancreas was assessed with infrared scanning of injected ICG. The NIR identified an ischaemic segment of the margin, which was further resected. The patient had no postoperative evidence of a pancreatic leak and was discharged home on postoperative day 18. Ischaemia of the remnant pancreas is a risk factor for pancreaticojejunostomy leak. Infrared ICG testing might help to identify these ischaemic segments, which can be excised before anastomosis, and reduce failure rates. PMID- 26160767 TI - In Vivo Tracking of Human Neural Progenitor Cells in the Rat Brain Using Magnetic Resonance Imaging Is Not Enhanced by Ferritin Expression. AB - Rapid growth in the field of stem cell research has generated a lot of interest in their therapeutic use, especially in the treatment of neurodegenerative diseases. Specifically, human neural progenitor cells (hNPCs), unique in their capability to differentiate into cells of the neural lineage, have been widely investigated due to their ability to survive, thrive, and migrate toward injured tissues. Still, one of the major roadblocks for clinical applicability arises from the inability to monitor these cells following transplantation. Molecular imaging techniques, such as magnetic resonance imaging (MRI), have been explored to assess hNPC transplant location, migration, and survival. Here we investigated whether inducing hNPCs to overexpress ferritin (hNPCs(Fer)), an iron storage protein, is sufficient to track these cells long term in the rat striatum using MRI. We found that increased hypointensity on MRI images could establish hNPC(Fer) location. Unexpectedly, however, wild-type hNPC transplants were detected in a similar manner, which is likely due to increased iron accumulation following transplantation-induced damage. Hence, we labeled hNPCs with superparamagnetic iron oxide (SPIO) nanoparticles to further increase iron content in an attempt to enhance cell contrast in MRI. SPIO-labeling of hNPCs (hNPCs-SPIO) achieved increased hypointensity, with significantly greater area of decreased T2* compared to hNPC(Fer) (p < 0.0001) and all other controls used. However, none of the techniques could be used to determine graft rejection in vivo, which is imperative for understanding cell behavior following transplantation. We conclude that in order for cell survival to be monitored in preclinical and clinical settings, another molecular imaging technique must be employed, including perhaps multimodal imaging, which would utilize MRI along with another imaging modality. PMID- 26160768 TI - Dexamethasone acts as a radiosensitizer in three astrocytoma cell lines via oxidative stress. AB - Glucocorticoids (GCs), which act on stress pathways, are well-established in the co-treatment of different kinds of tumors; however, the underlying mechanisms by which GCs act are not yet well elucidated. As such, this work investigates the role of glucocorticoids, specifically dexamethasone (DEXA), in the processes referred to as DNA damage and DNA damage response (DDR), establishing a new approach in three astrocytomas cell lines (CT2A, APP.PS1 L.1 and APP.PS1 L.3). The results show that DEXA administration increased the basal levels of gamma H2AX foci, keeping them higher 4h after irradiation (IR) of the cells, compared to untreated cells. This means that DEXA might cause increased radiosensitivity in these cell lines. On the other hand, DEXA did not have an apparent effect on the formation and disappearance of the 53BP1 foci. Furthermore, it was found that DEXA administered 2h before IR led to a radical change in DNA repair kinetics, even DEXA does not affect cell cycle. It is important to highlight that DEXA produced cell death in these cell lines compared to untreated cells. Finally and most important, the high levels of gamma-H2AX could be reversed by administration of ascorbic acid, a potent blocker of reactive oxygen species, suggesting that DEXA acts by causing DNA damage via oxidative stress. These exiting findings suggest that DEXA might promote radiosensitivity in brain tumors, specifically in astrocytoma-like tumors. PMID- 26160769 TI - Does the Janani Suraksha Yojana cash transfer programme to promote facility births in India ensure skilled birth attendance? A qualitative study of intrapartum care in Madhya Pradesh. AB - BACKGROUND: Access to facility delivery in India has significantly increased with the Janani Suraksha Yojana (JSY) cash transfer programme to promote facility births. However, a decline in maternal mortality has only followed secular trends as seen from the beginning of the decade well before the programme began. We, therefore, examined the quality of intrapartum care provided in facilities under the JSY programme to study whether it ensures skilled attendance at birth. DESIGN: 1) Non-participant observations (n=18) of intrapartum care during vaginal deliveries at a representative sample of 11 facilities in Madhya Pradesh to document what happens during intrapartum care. 2) Interviews (n=10) with providers to explore reasons for this care. Thematic framework analysis was used. RESULTS: Three themes emerged from the data: 1) delivery environment is chaotic: delivery rooms were not conducive to safe, women-friendly care provision, and coordination between providers was poor. 2) Staff do not provide skilled care routinely: this emerged from observations that monitoring was limited to assessment of cervical dilatation, lack of readiness to provide key elements of care, and the execution of harmful/unnecessary practices coupled with poor techniques. 3) Dominant staff, passive recipients: staff sometimes threatened, abused, or ignored women during delivery; women were passive and accepted dominance and disrespect. Attendants served as 'go-betweens' patients and providers. The interviews with providers revealed their awareness of the compromised quality of care, but they were constrained by structural problems. Positive practices were also observed, including companionship during childbirth and women mobilising in the early stages of labour. CONCLUSIONS: Our observational study did not suggest an adequate level of skilled birth attendance (SBA). The findings reveal insufficiencies in the health system and organisational structures to provide an 'enabling environment' for SBA. We highlight the need to ensure quality obstetric care prior to increasing coverage of facility births if cash transfer programmes like the JSY are to improve health outcomes. PMID- 26160770 TI - Determinants of marginalization and inequitable maternal health care in North Central Vietnam: a framework analysis. AB - BACKGROUND: Vietnam has achieved great improvements in maternal healthcare outcomes, but there is evidence of increasing inequity. Disadvantaged groups, predominantly ethnic minorities and people living in remote mountainous areas, do not gain access to maternal health improvements despite targeted efforts from policymakers. OBJECTIVE: This study identifies underlying structural barriers to equitable maternal health care in Nghe An province, Vietnam. Experiences of social inequity and limited access among child-bearing ethnic and minority women are explored in relation to barriers of care provision experienced by maternal health professionals to gain deeper understanding on health outcomes. DESIGN: In 2012, 11 focus group discussions with women and medical care professionals at local community health centers and district hospitals were conducted using a hermeneutic-dialectic method and analyzed for interpretation using framework analysis. RESULTS: The social determinants 'limited negotiation power' and 'limited autonomy' orchestrate cyclical effects of shared marginalization for both women and care professionals within the provincial health system's infrastructure. Under-staffed and poorly equipped community health facilities refer women and create overload at receiving health centers. Limited resources appear diverted away from local community centers as compensation to the district for overloaded facilities. Poor reputation for low care quality exists, and professionals are held in low repute for causing overload and resulting adverse outcomes. Country-wide reforms force women to bear responsibility for limited treatment adherence and health insight, but overlook providers' limited professional development. Ethnic minority women are hindered by relatives from accessing care choices and costs, despite having advanced insight about government reforms to alleviate poverty. Communication challenges are worsened by non-existent interpretation systems. CONCLUSIONS: For maternal health policy outcomes to become effective, it is important to understand that limited negotiation power and limited autonomy simultaneously confront childbearing women and health professionals. These two determinants underlie the inequitable economic, social, and political forces in Vietnam's disadvantaged communities, and result in marginalized status shared by both in the poorest sectors. PMID- 26160771 TI - Oral health information from the dentist to the diabetologist. AB - BACKGROUND: Diabetes care includes annual evaluation of micro- and macrovascular complications, however, oral pathologies are not included. We studied retrieving oral health information, in particular periodontal disease, from the dentist and studied the association between the reported periodontal condition and variables of both diabetes and dental care. METHODS: During their annual comprehensive diabetes evaluation, patients were asked to deliver an oral health questionnaire (OHQ) to their dentist. Based on the returned OHQs, the process of retrieving oral health information from the dentist was analyzed. In addition, reported oral health measures with special emphasis to periodontitis, using a Periodontal Screening Index (PSI), were related to diabetes-related variables. RESULTS: We included 889 patients of whom 102 patients (11%) did not visit a dentist at all and 252 (28%) were edentulous. The response rate was <50% for oral information on patients with diabetes. For the second aim, OHQs of 207 patients could be further analyzed. A moderate to high PSI-score was found in 106 patients, of whom 65% were untreated for periodontitis. Furthermore high PSI-scores were associated with poor oral hygiene, soft tissue pathologies and periodontal treatment, but not significantly with glycemic control and presence of diabetes complications. CONCLUSION: The transfer of information from the dentist to the diabetologist is far from optimal. An OHQ can be a valuable tool for the identification of patients with diabetes with poor oral health especially untreated periodontal disease, which is helpful for proper diabetes management. PMID- 26160772 TI - The influence of gender on the communication skills assessment of medical students. AB - BACKGROUND: Opinions on the interaction between the genders of standardized patients and examinees are controversial. Our study sought to determine the influence of gender on communication skills assessment in Eastern country. METHODS: We recruited year 5 medical students from a medical college in Taiwan. They were assigned to obtain informed consent from either male or female age matched standardized patients. Their performance was rated by standardized checklist rating scores and global rating scores. Either male or female examiners rated their performance. RESULTS: A total of 253 medical students (166 male students and 87 female students) were recruited. The checklist rating scores for students interacting with male standardized patients were significantly lower than the scores for interactions with female standardized patients (male examiners, P=0.006; female examiners, P=0.001). For male students, the checklist rating scores were significantly lower for male standardized patients than for female standardized patients (male examiners, P=0.006; female examiners, P=0.008). For male standardized patients, male students had significantly lower checklist rating scores than female students when rated by male examiners (P=0.044). The global rating scores were similar except when female students interacted with male and female SPs and when rated by female examiners (P=0.004). CONCLUSION: The gender of standardized patients influences communication skills assessment. In terms of checklist rating scores, female standardized patients seem preferable to minimize potential gender effects. In the best interest of students, global rating score may be preferable to checklist rating score, especially for male examinees. PMID- 26160773 TI - Effects of Childhood Experience of Violence Between Parents and/or Parent-to Child Violence on Young Israeli Adults' Global Self-Esteem. AB - The study examines long-term effects of family violence in childhood (violence between parents and/or parent-to-child violence) on adult self-esteem. Data were derived from a sample of 352 university students. Findings show that young adults not exposed to family violence in childhood report the highest self-esteem; lower self-esteem reports were by those experiencing one type of family violence; the lowest self-esteem was reported by those who experienced two types of family violence. In the latter two groups, self-esteem was also affected by frequency of violence. A linkage was identified between the family violence types examined: The more frequent one type of violence, the more frequent the other type. Theoretical and practical implications for the study of effects of family violence on child development are discussed. PMID- 26160774 TI - Gurinder Singh Grewal: can the new medical council president clean up medicine in Punjab? PMID- 26160777 TI - Microchipping: BVA survey suggests a quarter of dogs remain unchipped. PMID- 26160775 TI - Beyond Adherence: Health Care Disparities and the Struggle to Get Screened for Colon Cancer. AB - Dominant health care professional discourses on cancer take for granted high levels of individual responsibility in cancer prevention, especially in expectations about preventive screening. At the same time, adhering to screening guidelines can be difficult for lower income and under-insured individuals. Colorectal cancer (CRC) is a prime example. Since the advent of CRC screening, disparities in CRC mortality have widened along lines of income, insurance, and race in the United States. We used a community-engaged research method, Photovoice, to examine how people from medically under-served areas experienced and gave meaning to CRC screening. In our analysis, we first discuss ways in which participants recounted screening as a struggle. Second, we highlight a category that participants suggested was key to successful screening: social connections. Finally, we identify screening as an emotionally laden process that is underpinned by feelings of uncertainty, guilt, fear, and relief. We discuss the importance of these findings to research and practice. PMID- 26160776 TI - Epidemiological dynamics of nephropathia epidemica in the Republic of Tatarstan, Russia, during the period of 1997-2013. AB - This report summarizes epidemiological data on nephropathia epidemica (NE) in the Republic of Tatarstan, Russia. NE cases identified in the period 1997-2013 were investigated in parallel with the hantavirus antigen prevalence in small rodents in the study area. A total of 13 930 NE cases were documented in all but one district of Tatarstan, with most cases located in the central and southeastern districts. The NE annual incidence rate exhibited a cyclical pattern, with the highest numbers of cases being registered once in every 3-5 years. The numbers of NE cases rose gradually from July to November, with the highest morbidity in adult males. The highest annual disease incidence rate, 64.4 cases/100 000 population, was observed in 1997, with a total of 2431 NE cases registered. NE cases were mostly associated with visiting forests and agricultural activities. The analysis revealed that the bank vole Myodes glareolus not only comprises the majority of the small rodent communities in the region, but also consistently displays the highest hantavirus prevalence compared to other small rodent species. PMID- 26160778 TI - Food standards: Judge backs OV's decision on unfit carcase. PMID- 26160779 TI - Bovine TB: Online map shows TB breakdowns. PMID- 26160780 TI - Bovine TB: Views invited on actions to combat bovine TB in Northern Ireland. PMID- 26160781 TI - Badger removal to begin in NI's 'TVR' project. PMID- 26160782 TI - Profession: Food for thought in the inaugural Ballyedmond Lecture. PMID- 26160783 TI - Scotland to consult on use of electronic collars. PMID- 26160785 TI - RCVS annual report. PMID- 26160784 TI - RCVS Council: RCVS Council agrees changes to routes of entry to RCVS Fellowship. PMID- 26160786 TI - Specialisation: Deadline extended for specialist status applications. PMID- 26160787 TI - Animal health: Tackling a mitey problem. AB - The poultry ectoparasite Dermanyssus gallinae, known to poultry farmers as 'red mite', has a negative impact on animal health and is a vector of viruses and bacteria. It also sometimes attacks poultry farm workers, and human infestations have been reported originating from pigeons' nests in urban areas. A European project is currently investigating synergistic and holistic approaches to improving the health, welfare and productivity of laying hens through more effective prevention and control of the red mite. Kathryn Bartley reports from a two-day conference held in Italy in May, which provided an update on progress with the project. PMID- 26160788 TI - Charities: Getting the message across on responsible ownership. PMID- 26160789 TI - SAC C VS disease surveillance report: Skin lesions in a heifer with malignant catarrhal fever. PMID- 26160790 TI - Slugs and Angiostrongylus vasorum--how much do we know? PMID- 26160791 TI - Veterinary medicines: Recognised veterinary practice and clinical trials. PMID- 26160792 TI - Antimicrobial resistance: Multidrug resistance in enterotoxigenic K99 E coli infection in lambs. PMID- 26160799 TI - Fifty years a vet. AB - Agnes Winter wanted to go to Bristol vet school to become a cattle vet, but ended up studying at Liverpool and ultimately became a sheep vet. Here, she discusses the choices she made based on the opportunities available. PMID- 26160800 TI - First-year student diary. AB - Rosie Perrett has finished her first year of studies at Liverpool and is awaiting her exam results. In the meantime, EMS placements will give her the chance to consolidate what she has learnt. PMID- 26160801 TI - Pluripotent Stem Cells to Rebuild a Kidney: The Lymph Node as a Possible Developmental Niche. AB - Kidney disease poses a global challenge. Stem cell therapy may offer an alternative therapeutic approach to kidney transplantation, which is often hampered by the limited supply of donor organs. While specific surface antigen markers have yet to be identified for the analysis and purification of kidney stem/progenitor cells for research or clinical use, the reprogramming of somatic cells to pluripotent cells and their differentiation into the various kidney lineages might represent a valuable strategy to create a renewable cell source for regenerative purposes. In this review, we first provide an overview of kidney development and explore current knowledge about the role of extra- and intrarenal cells in kidney repair and organogenesis. We then discuss recent advances in the 1) differentiation of rodent and human embryonic stem cells (ESCs) into renal lineages; 2) generation of induced pluripotent stem cells (iPSCs) from renal or nonrenal (kidney patient-derived) adult cells; 3) differentiation of iPSCs into renal lineages; and 4) direct transcriptional reprogramming of adult renal cells into kidney progenitor cells. Finally, we describe the lymph node as a potential three-dimensional (3D) in vivo environment for kidney organogenesis from pluripotent stem cells. PMID- 26160802 TI - Temperature Effects on the Development and Reproduction of Three Trichogramma (Hymenoptera: Trichogrammatidae) Species Reared on Trichoplusia ni (Lepidoptera: Noctuidae) Eggs. AB - The cabbage looper, Trichoplusia ni (Hubner) (Lepidoptera: Noctuidae) is a generalist species and an important pest of Brassicaceae worldwide. Egg parasitoids are a feasible alternative for the control of this species. We evaluated the suitability of T. ni eggs as hosts for three Trichogramma Westwood (Hymenoptera: Trichogrammatidae) species and their tolerance to survive and develop within a range of temperatures between 15 and 30 degrees C under laboratory conditions. The species evaluated were Trichogramma pretiosum Riley, Trichogramma atopovirilia Oatman and Platner, and Trichogramma acacioi Brun, Moraes and Soares. Parasitism rate was affected by temperature, parasitoid species, and by the interaction between these two factors. Parasitoids developed and reproduced in the range of temperatures evaluated, but Trichog. acacioi failed to parasitize T. ni eggs at 30 degrees C. The highest parasitism rates of Trichog. atopovirilia and Trichog. pretiosum occurred at 20 and 25 degrees C and Trichog. acacioi at 25 degrees C, with parasitism rate above 70% in the three species. Parasitoid emergence was not affected by temperature or species. The estimated thermal constant and lower temperature threshold were 134.6 DD and 10.6 degrees C for Trichog. pretiosum and 130.1 DD and 11.2 degrees C for Trichog. atopovirilia. The results demonstrated that Trichog. pretiosum and Trichog. atopovirilia are the most suitable species for the control of T. ni, as they can remain active throughout the year in subtropical regions. PMID- 26160803 TI - Variation in Baiting Intensity Among CO2-Baited Traps Used to Collect Hematophagous Arthropods. AB - Hematophagous arthropods transmit the etiological agents of numerous diseases and as a result are frequently the targets of sampling to characterize vector and pathogen populations. Arguably, the most commonly used sampling approach involves traps baited with carbon dioxide. We report results of a laboratory study in which the performance of carbon dioxide-baited traps was evaluated using measures of baiting intensity, the amount of carbon dioxide released per unit time during trap deployment. We evaluated the effects of trap design, carbon dioxide source, and wind speed on baiting intensity and documented significant effects of these factors on the length of sampling (time to baiting intensity = 0), maximum baiting intensity, and variation in baiting intensity during experimental trials. Among the three dry ice-baited trap types evaluated, traps utilizing insulated beverage coolers as dry ice containers sampled for the longest period of time, had the lowest maximum but most consistent baiting intensity within trials and were least sensitive to effects of wind speed and dry ice form (block vs. pellet) on baiting intensity. Results of trials involving traps baited with carbon dioxide released from pressurized cylinders suggested that this trap type had performance comparable to dry ice-baited insulated cooler traps but at considerably higher cost. PMID- 26160804 TI - Influence of Constant Temperature on Reproductive Parameters of Holotrichia oblita (Coleoptera: Scarabaeidae). AB - Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae) is a major pest both in field crops and forests because the larvae could eat the roots of most crops in the field, and the adults damage the leaves of trees and field crops. In this study, we focused on the effects of temperature on H. oblita reproductive parameters. The results indicated H. oblita female adults at 25 degrees C could lay more eggs (84.0 eggs per female) and have the shortest preoviposition period (19.1 d), the greatest oviposition rate (2.8 eggs per female per 3 d), and largest percentage of life span spent in oviposition (59.5%). The longevity and the time to 50% egg laying decreased with increasing temperature, and female longevity was always longer than male longevity. The preoviposition and postoviposition period decreased with increasing temperature from 15 to 25 degrees C and then increased when the temperature increased from 25 to 30 degrees C. These results show that 25 degrees C is the optimal temperature for reproduction of H. oblita. PMID- 26160805 TI - Understanding the challenges to facilitating active learning in the resident conferences: a qualitative study of internal medicine faculty and resident perspectives. AB - BACKGROUND: In the Next Accreditation System, the Accreditation Council for Graduate Medical Education outlines milestones for medical knowledge and requires regular didactic sessions in residency training. There are many challenges to facilitating active learning in resident conferences, and we need to better understand resident learning preferences and faculty perspectives on facilitating active learning. The goal of this study was to identify challenges to facilitating active learning in resident conferences, both through identifying specific implementation barriers and identifying differences in perspective between faculty and residents on effective teaching and learning strategies. METHODS: The investigators invited core residency faculty to participate in focus groups. The investigators used a semistructured guide to facilitate discussion about learning preferences and teaching perspectives in the conference setting and used an 'editing approach' within a grounded theory framework to qualitative analysis to code the transcripts and analyze the results. Data were compared to previously collected data from seven resident focus groups. RESULTS: Three focus groups with 20 core faculty were conducted. We identified three domains pertaining to facilitating active learning in resident conferences: barriers to facilitating active learning formats, similarities and differences in faculty and resident learning preferences, and divergence between faculty and resident opinions about effective teaching strategies. Faculty identified several setting, faculty, and resident barriers to facilitating active learning in resident conferences. When compared to residents, faculty expressed similar learning preferences; the main differences were in motivations for conference attendance and type of content. Resident preferences and faculty perspectives differed on the amount of information appropriate for lecture and the role of active participation in resident conferences. CONCLUSION: This study highlights several challenges to facilitating active learning in resident conferences and provides insights for residency faculty who seek to transform the conference learning environment within their residency program. PMID- 26160806 TI - Contribution of Rare and Common Genetic Variants to Plasma Lipid Levels and Carotid Stiffness and Geometry: A Substudy of the Paris Prospective Study 3. AB - BACKGROUND: We assess the contribution of common and rare putatively functional genetic variants (most of them coding) present on the Illumina exome Beadchip to the variability of plasma lipids and stiffness of the common carotid artery. METHODS AND RESULTS: Measurements were obtained from 2283 men and 1398 women, and after filtering and exclusion of monomorphic variants, 32,827 common (minor allele frequency >0.01) and 68,770 rare variants were analyzed. A large fraction of the heritability of plasma lipids is attributable to variants present on the array, especially for triglycerides (fraction of variance attributable to measured genotypes: V(G)/V(p)=31.4%, P<3.1*10(-11)) and high-density lipoprotein cholesterol (V(G)/V(p)=26.4%, P<4.2*10(-12)). Plasma lipids were associated with common variants located in known candidate genes, but no implication of rare variants could be established. Gene sets for plasma lipids, blood pressure, and coronary artery disease were defined on the basis of recent meta-analyses of genome-wide association studies. We observed a strong association between the plasma lipids gene set and plasma lipid variables, but none of the 3 genome-wide association studies gene sets was associated with the carotid parameters. Significant V(G)/V(p) ratios were observed for external (14.5%, P<2.7*10(-5)) and internal diameter (13.4%, P<4.3*10(-4)), stiffness (12.5%, P<8.0*10(-4)), intima media thickness (10.6%, P<7.9*10(-4)), and wall cross-sectional area (13.2%, P<2.4*10(-5)). A significant association was observed between the common rs2903692 polymorphism of the CLEC16A gene and the internal diameter (P<4.3*10( 7)). CONCLUSIONS: These results suggest an involvement of CLEC16A, a gene that has been reported to be associated with immune disorders, in the modulation of carotid vasodilatation. PMID- 26160807 TI - Royal college strengthens its guideline on female genital mutilation. PMID- 26160808 TI - [Clinical and Laboratory Diagnosis of Central Nervous System Infections]. AB - Central nervous system (CNS) infections, including acute encephalitis, bacterial meningitis, tuberculous meningitis, and fungal meningitis, represent a potentially life-threatening neurological emergency. An etiological diagnosis of CNS infection is made a definite diagnosis based on the identification of pathogenic agents in the CNS using cerebrospinal fluid (CSF) smears or cultures, the identification of pathogenic antigens in CSF, the identification of pathogenic products in brain tissues or CSF with polymerase chain reaction (PCR), or the identification of specific antibody responses in CSF. Since time is required to obtain results from these laboratory tests, initial empirical treatments for the suspected CNS infection are required. The optimal specimen sampling and delivery is an essential requirement to reach the definite diagnosis. Nucleic acid amplification tests, such as PCR assays, show high sensitivity and specificity in detecting pathogens from CSF. In Japan, most genetic tests for pathogenic agents are performed as part of academic research. The number of commercially available genetic tests is limited. Moreover, no genetic tests for pathogenic agents in the CSF are covered by the national health insurance system in Japan. To manage the continuity of genetic tests, this inefficient system should be improved. PMID- 26160809 TI - [Current Clinical Management of Bacterial Meningitis]. AB - The recent protocols for the clinical management of bacterial meningitis (BM) is reviewed. BM can present as an acute fulminant disease that progresses rapidly in a few hours or as a subacute infection that progressively worsens during several days. The mortality rate with BM and the frequency of neurologic sequelae among those who survive are high. BM is thus a life-threatening neurological emergency. Early recognition, efficient decision-making, and the rapid institution of therapy can be lifesaving. Empirical therapy should be initiated promptly whenever BM is a significant diagnostic consideration. The Infectious Diseases Society of America (2004) and European Federation of Neurological Societies (2008) reported an initial management approach of BM. The guidelines for the clinical management of BM in Japan were published in 2007, and the revision was published in December 2014. These initial therapeutic management protocols for BM differ for every country. The reasons for the different initial therapeutic management are based on the following strategies. The choice of the specific antimicrobial agents for the initial treatment is based on the current knowledge of the antimicrobial susceptibility patterns of these pathogens in the area. For the initial treatment, the assumption should be that antimicrobial resistance is likely. The choice of an empirical antibiotic in BM may be influenced by a number of factors, including the patient's age, systemic symptoms, and local pattern of bacterial resistance. If there is no epidemiologic evidence in Japan, a committee investigates and collects data in the revised Japanese guidelines 2014 for the clinical management of BM. PMID- 26160810 TI - [Molecular Approaches for the Diagnosis of Central Nervous System Infections]. AB - In recent years, molecular microbiology techniques have proven to be a useful supplement to conventional assays not only in identification of strains from culture, but also in direct detection of pathogens from clinical specimens. This review explores the application of molecular diagnostic techniques for infectious diseases in certain clinical contexts. It aims to assess how these molecular techniques can be integrated to enhance diagnostic capabilities for infectious diseases of the central nervous system. Finally, it emphasizes the need for close collaboration between physicians and clinical microbiologists when considering molecular diagnostics from unusual specimens/cases, because assays must be customized according to the clinical settings. PMID- 26160811 TI - [The Role of Imaging in Central Nervous System Infections]. AB - Many infections invade the central nervous system. Magnetic resonance imaging (MRI) is the main tool that is used to evaluate infectious lesions of the central nervous system. The useful sequences on MRI are dependent on the locations, such as intra-axial, extra-axial, and spinal cord. For intra-axial lesions, besides the fundamental sequences, including T1-weighted images, T2-weighted images, and fluid-attenuated inversion recovery (FLAIR) images, advanced sequences, such as diffusion-weighted imaging, diffusion tensor imaging, susceptibility-weighted imaging, and MR spectroscopy, can be applied. They are occasionally used as determinants for quick and correct diagnosis. For extra-axial lesions, understanding the differences among 2D-conventional T1-weighted images, 2D-fat saturated T1-weighted images, 3D-Spin echo sequences, and 3D-Gradient echo sequence after the administration of gadolinium is required to avoid wrong interpretations. FLAIR plus gadolinium is a useful tool for revealing abnormal enhancement on the brain surface. For the spinal cord, the sequences are limited. Evaluating the distribution and time course of the spinal cord are essential for correct diagnoses. We summarize the role of imaging in central nervous system infections and show the pitfalls, key points, and latest information in them on clinical practices. PMID- 26160813 TI - [Human T-Lymphotropic Virus Type I-Associated Myelopathy]. AB - Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) is a chronic progressive myelopathy that is characterized by spastic paraparesis with bladder dysfunction that is derived from bilateral pyramidal tract involvement and neurogenic bladder, respectively. The primary neuropathological feature of HAM is chronic inflammation in the spinal cord, mainly the lower thoracic cord, which is characterized by perivascular cuffing and parenchymal infiltration of mononuclear cells. Although it is still unclear why only a very small proportion of HTLV-I carriers develop HAM, the key player in the pathogenesis of HAM is the increase of activated HTLV-I-infected cells in the peripheral blood. The exact cellular and molecular events underlying the induction of chronic inflammation in the spinal cord by HTLV-I are still unclear. However, a long-standing bystander mechanism, such as the destruction of surrounding nervous tissue by the interaction between HTLV-I-infected CD4+ T cells and HTLV-I-specific cytotoxic T cells in the spinal cord, with the cooperation of the positive feedback loop of inflammation that is derived from the migrated HTLV-I-infected cells is probably critical in the immunopathogenesis of HAM. In this review, recent advances in several fields toward the elucidation of the pathomechanisms concomitant with the establishment of new therapeutic strategies in HAM will be discussed along with an overview of the clinical features. PMID- 26160812 TI - [Neurologic Complications in HPV Vaccination]. AB - A relatively high incidence of chronic limb pain, frequently complicated by violent, tremulous involuntary movements, has been noted in Japanese girls following human papillomavirus vaccination. The average incubation period after the first dose of the vaccine was 5.47 +/- 5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the feet, limb pain, and weakness. The skin temperature of the girls with limb symptoms was slightly lower in the fingers and moderately lower in the toes. Digital plethysmograms revealed a reduced peak of the waves, especially in the toes. Limb symptoms of the affected girls were compatible with the diagnostic criteria for complex regional pain syndrome. The Schellong test identified a significant number of patients with orthostatic hypotension and a few with postural orthostatic tachycardia syndrome. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined. The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the patients was psychosomatic disease. Recently, delayed manifestation of cognitive dysfunction in the post-vaccinated girls has attracted attention. The symptoms include memory loss and difficulty in reading textbooks and/or calculation. PMID- 26160814 TI - [Influenza-Associated Encephalopathy]. AB - Influenza-associated encephalopathy is a syndrome that chiefly manifests consciousness disturbance provoked by influenza. It is defined pathologically as acute neurological dysfunction that results from non-inflammatory brain edema. The clinical picture is so diverse that many clinical subtypes and multiple pathologies have been proposed to date. Influenza-associated encephalopathy is diagnosed and treated according to the disease guideline in Japan, which has improved the outcome of influenza-associated encephalopathy. Although influenza associated encephalopathy had been regarded as a childhood disease in Japan, adult cases and those in the US and Europe have been reported since the 2009 pandemic. Therefore, influenza-associated encephalopathy has been spotlighted. PMID- 26160815 TI - [Antecedent Infections in Guillain-Barre Syndrome: Knowledge in Clinical Practice]. AB - Guillain-Barre syndrome (GBS) is a post-infectious disease in which a diversity of pathogenetic factors and clinical features is surely determined by the type of preceding infections. It is necessary in clinical practice and research to identify the antecedent infectious agent in each case. Several lines of evidence indicate that the ganglioside-like epitopes on the infectious agents induce the production of anti-ganglioside autoantibodies and thereby cause GBS. This makes it possible to evaluate the causal significance of the pathogen by examining the cross-reactivity of the detected autoantibodies with outer antigens of the pathogens, although such an investigation is practical only when the pathogen is successfully isolated from the patients. The term "antecedent infection" should be strictly used in the situation in which the infection is thought to be closely related to the development of GBS but not for the situation without findings that suggest such a relationship. Simple but non-validated criteria for the judgment of antecedent infection in each GBS case are proposed in this review in order to prevent numerous and unreliable suspicions of "new" and "unknown" prior infectious agents of GBS, which are only built on the precedence in the disease. PMID- 26160816 TI - [Association between Multiple Sclerosis or Neuromyelitis Optica and Epstein-Barr Virus]. AB - Accumulated evidence shows an association between Epstein-Barr viral (EBV) infection and multiple sclerosis (MS). In particular, EBV infections before the onset of MS, particularly in childhood, is associated with the pathogenesis of MS. Meanwhile, the association between neuromyelitis optica (NMO) and infectious agents has been reported, but is currently unclear. Recently we studied the association between NMO and EBV and compared between MS and EBV. The results showed that MS is associated with past infections of EBV as the results of previous studies. In contrast, NMO is associated with the reactivation of EBV. PMID- 26160817 TI - [Neuropathology of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy]. AB - The pathological findings of natalizumab-associated progressive multifocal leukoencephalopathy (PML) are reviewed. In addition to the classical pathology of PML including the presence of enlarged abnormal astrocytes, intranuclear inclusions mainly found within large swollen oligodendrocytes and abundant myelin laden macrophages/microglia, massive perivascular and parenchymal mononuclear cell infiltration was observed. The latter pathologic picture is that of immune reconstitution inflammatory syndrome (IRIS), and most of these infiltrating cells are CD8-positive T cells. Because IRIS inevitably occurs after the cessation of natalizumab therapy due to the development of PML and subsequent plasma exchange, most of the published pathologic pictures of natalizumab-associated PML patients were a mixture of PML and PML-IRIS. PML-IRIS is also characterized by fewer oligodendroglial viral inclusions and fewer cells that are immunoreactive against anti-JCV antibodies. These findings suggest the effective removal of JCV after the return of normal immune-surveillance in the central nervous system, but clinicians should be aware that JCV elimination is not complete under the IRIS condition, and the immunosuppressive therapy against IRIS should be carefully performed. Mononuclear cell infiltration in natalizumab-associated PML-IRIS patients was much more prominent than that in HIV-associated PML-IRIS patients, reflecting the retained, even enhanced, systemic immunities in patients treated by natalizumab. PMID- 26160818 TI - [Pathology of Opportunistic Infection of the Central Nervous System]. AB - Opportunistic pathogens affecting the central nervous system include bacteria, fungi, protozoa, and viruses, and infection with these microorganisms exhibits varied histopathological findings. In opportunistic infections, the inflammatory and reparative mechanisms of the affected tissues are generally weak, reflecting a decrease of the protective immunological response of the host. In recent years, the so-called "immune reconstitution inflammatory syndrome," which is caused by abrupt restoration of the immunological activity due to therapy, has emerged as a new clinicopathological problem, especially in acquired immunodeficiency syndrome patients. In this comprehensive review, detailed classical histopathological descriptions on the various aspects of opportunistic infection affecting the central nervous system are provided, with the intention to provide a basis for further molecular pathological studies. PMID- 26160820 TI - [Update on Herpes Simplex Encephalitis]. AB - Herpes simplex encephalitis (HSE), which is caused by the herpes simplex virus (HSV), is a severe neuro-infectious disease characterized by high mortality and morbidity. We reviewed the pathomechanism, diagnosis, and treatment of HSE based on recent progress in the field. The highlighted mechanism of HSE in this review is immune-mediated tissue damage caused by host immunity. Major symptoms of HSE include psychiatric alteration, Kluver-Bucy syndrome, and amnesia, caused by frequent involvement of the limbic system. An important differential diagnosis of HSE is autoimmune limbic encephalitis, including anti-N-methyl-D-aspartate receptor encephalitis, and anti-voltage-gated K+ channel encephalitis. HSE is definitely diagnosed based on the detection of HSV-DNA by polymerase chain reaction and/or the detection of HSV-IgG antibody in the cerebrospinal fluid (CSF). Repeated CSF examinations are required for the accurate diagnosis of HSE. Acyclovir (ACV) plays a central role in the treatment of HSE, and its early initiation is essential for good outcome in patients with HSE. Acute administration of corticosteroids for HSE is controversial; a randomized, double blind, placebo-controlled trial to investigate the efficacy of add-on corticosteroids to ACV is ongoing. PMID- 26160819 TI - [Human Herpesvirus-6 Encephalitis in Allogeneic Hematopoietic Stem Cell Transplantation]. AB - The reactivation of human herpesvirus-6B (HHV-6B) is common after allogeneic hematopoietic cell transplantation (allo-HCT), and it is sporadically associated with the development of HHV-6 encephalitis. HHV-6 encephalitis typically develops around 2-6 weeks after allo-HCT, and it is characterized by short-term memory loss. Magnetic resonance imaging typically shows bilateral signal abnormalities in the limbic system. The incidence of HHV-6 encephalitis is reportedly 0-11.6% after bone marrow or peripheral blood stem cell transplantation and 4.9-21.4% after cord blood transplantation. The mortality of HHV-6 encephalitis is high, and survivors are often left with serious sequelae. Antiviral therapy using foscarnet or ganciclovir is recommended for the treatment of HHV-6 encephalitis, but the efficacy of the currently available treatment is insufficient once HHV-6 encephalitis has developed. The elucidation of the pathogenesis of HHV-6 encephalitis and the establishment of preventative therapy are needed to overcome this disease. PMID- 26160821 TI - [Current Trends in the Treatment of Prion Disease]. AB - Prion disease refers to a group of neurodegenerative disorders characterized by a relentlessly progressing clinical course leading to death. The pathogenesis of prion disease is the conversion of a normal type prion protein (PrP(C)) into a pathological isoform with protease resistance (PrP(Sc)), which accumulates in the brain. A number of therapeutic agents, including quinacrine, doxycycline, and pentosan polysulphate have shown preventive effects against the conversion of PrP(C) into PrP(Sc) in experimental studies; however, none of these agents have shown satisfactory efficacy in clinical trials. As the clinical course of prion disease varies, the design of clinical trials has been particularly difficult. These limitations must be overcome, and it is necessary to determine a basis for clinical trials with the new candidate agents. PMID- 26160822 TI - [Progress in Antiretroviral Therapy and HAND]. AB - Today, over 20,000 people are thought to be infected with human immunodeficiency virus (HIV) in Japan. Antiretroviral therapy (ART) has substantially improved the prognosis of HIV-infected patients, but long-term medication generates new problems. This article overviews the progress of anti-HIV therapies and explains the concept of HIV-associated neurocognitive disorders (HAND) as a noted complication of HIV infection. PMID- 26160823 TI - [Diagnostic Criteria for Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex in the Kii Peninsula, Japan]. AB - The diagnostic criteria for amyotrophic lateral sclerosis/parkinsonism-dementia complex in the Kii peninsula of Japan (Kii ALS/PDC) have been proposed. Muro disease has been considered an endemic neurodegenerative disease in the southern part of the Kii peninsula. Recent intensive and comprehensive research has revealed it to be a complex and genetically heterogeneous disease. At present, there are four subtypes of Muro disease: sporadic amyotrophic lateral sclerosis (ALS), Kii ALS/PDC with tauopathy, ALS with C9orf72 gene mutation, and ALS with optineurin gene mutation. The present criteria are applicable to only one of these subtypes, Kii ALS/PDC with tauopathy, which is quite similar to ALS/PDC in Guam. PMID- 26160824 TI - [A Patient with Probable Dementia with Lewy Bodies and Positive Autoantibodies against the Anti-NH2-terminal of alpha-Enolase]. AB - Dementia with Lewy bodies (DLB) is clinically characterized by progressive dementia that is frequently accompanied by neurological and psychiatric manifestations. Hashimoto's encephalopathy (HE) is a rare autoimmune disease with neurological and psychiatric manifestations that is not well understood. However, this disease has attracted growing attention as a treatable dementia. Although autoimmune mechanisms are thought to play a pathogenic role in HE, the etiology of the disease remains unclear. Recently, it was reported that the serum in patients with HE is frequency positive for autoantibodies against the anti NH2-terminal of alpha-enolase (anti-NAE), indicating a useful serological diagnostic marker for HE. We report the case of an 81-year-old Japanese woman with probable DLB and hypothyroidism. In her serum, elevated anti thyroid antibodies and positive autoantibodies against anti-NAE were observed. Elevated levels of anti-glutamate receptor epsilon2 subunit (GluRepsilon2) antibodies were also detected in her cerebrospinal fluid. Because her clinical condition became stable after treatment with cholinesterase inhibitor, levodopa, and levothyroxine, immunotherapy was not performed. Although the relationship between autoimmunity and cognitive decline in this patient was unclear, the present observations suggest the coexistence of neurodegeneration and autoimmunity as the underlying pathogenic mechanism. PMID- 26160826 TI - Correction. PMID- 26160827 TI - Correction. PMID- 26160825 TI - Estimating the ratio of multivariate recurrent event rates with application to a blood transfusion study. AB - In comparative effectiveness studies of multicomponent, sequential interventions like blood product transfusion (plasma, platelets, red blood cells) for trauma and critical care patients, the timing and dynamics of treatment relative to the fragility of a patient's condition is often overlooked and underappreciated. While many hospitals have established massive transfusion protocols to ensure that physiologically optimal combinations of blood products are rapidly available, the period of time required to achieve a specified massive transfusion standard (e.g. a 1:1 or 1:2 ratio of plasma or platelets:red blood cells) has been ignored. To account for the time-varying characteristics of transfusions, we use semiparametric rate models for multivariate recurrent events to estimate blood product ratios. We use latent variables to account for multiple sources of informative censoring (early surgical or endovascular hemorrhage control procedures or death). The major advantage is that the distributions of latent variables and the dependence structure between the multivariate recurrent events and informative censoring need not be specified. Thus, our approach is robust to complex model assumptions. We establish asymptotic properties and evaluate finite sample performance through simulations, and apply the method to data from the PRospective Observational Multicenter Major Trauma Transfusion study. PMID- 26160828 TI - Pharmacy chain leaves US Chamber of Commerce over tobacco policy. PMID- 26160829 TI - Voluntary Organizations and Community Groups as New Partners in Diabetes Self management and Education: A Critical Interpretative Synthesis. AB - PURPOSE: The purpose of this study is to critically review the literature on the role and work of voluntary organizations and community groups and volunteers in diabetes self-management programs. It seeks to explain how these organizations are located and could be integrated further within a broader system of support. METHODS: A critical interpretative synthesis of the literature was undertaken as part of the conceptual development of a European research project. Evidence (2000 November 2014) was searched in databases, with the use of key terms, and limited to the languages of the participating countries. This was supplemented by an additional hand search and snowballing technique. A total of 21 articles were included in the review. RESULTS: Evidence regarding the involvement of voluntary organizations in diabetes self-management programs mainly related to: the nature and remit of their work, responsibilities, and attributes; key strategies of programs accounting for success; motivations/barriers for engaging in volunteering participation; relationships between volunteers and users; and connections/tensions with formal services. CONCLUSIONS: This review has uncovered a range of facets of voluntary organizations and community groups relevant for supporting diabetes self-management such as the context within which they act and the nature of relationships developed with community and health services. The principles of "assistance, support, sharing, and link" seem essential for this voluntary initiative in self-management to establish effective reciprocal collaboration with health professionals. PMID- 26160830 TI - Routine Screening of Coronary Artery Disease With Computed Tomographic Coronary Angiography in Place of Invasive Coronary Angiography in Patients Undergoing Transcatheter Aortic Valve Replacement. AB - BACKGROUND: Coronary artery disease (CAD) screening is required before transcatheter aortic valve implantation (TAVR). Although invasive coronary angiography (CA) remains the gold standard for CAD assessment, computed tomographic CA (CTCA) could be a safe and effective noninvasive alternative for CAD screening in patients undergoing TAVR. METHODS AND RESULTS: From November 2007 to May 2013, all patients undergoing TAVR at our institution were included in the study cohort. CTCA was used as first-line imaging tool for CAD screening. Invasive CA was performed when any of the following were present: coronary anatomy at CTCA was not evaluable and presence of significant CAD at CTCA. The primary objective was to compare major adverse cardiovascular and cerebrovascular events at 30 days and 1 year between patients who performed CTCA as only screening test and those who performed CTCA and invasive CA. Of 491 patients treated with TAVR, 375 (76.3%) performed only CTCA, whereas 116 (21.7%) underwent also CA. No differences were present in crude major adverse cardiovascular and cerebrovascular event rates at 30 days and 1 year between the 2 groups. After multivariable adjustment, CTCA performed alone was not associated with higher risk of MACE at 1 year of follow-up (hazard ratio, 0.89; 95% confidence interval, 0.49-1.60; P=0.69). CONCLUSIONS: CTCA performed as a routine noninvasive imaging tool in patients undergoing TAVR seems safe and effective allowing, with a single test, acquisition of information on aortic annulus anatomy, peripheral access sites, and evaluation of coronary anatomy. PMID- 26160831 TI - Minimalist Approach to Evaluating Patients for Transcatheter Aortic Valve Replacement. PMID- 26160832 TI - Fit-for-Purpose Radio Receptor Assay for the Determination of Growth Hormone Secretagogues in Urine. AB - The everlasting pharmacological development is continuously producing new substances with potential doping abuse. Among these, secretagogues are very prone to misuse by athletes for their properties to release growth hormone (GH) and some limitations in the actual analytical methods to detect them. In this paper, an in-depth study on the key variables of the radio receptor method previously developed by our group is performed and a fit-for-purpose protocol is established. Thus, this sensitive and robust screening method is proposed as an intelligent and preventive antidoping method to detect new growth hormone secretagogues (GHSs) in exceptional suspicious urine samples obtained from athletes and will support the current detection methods based on liquid chromatography-mass spectrometry (LC-MS). PMID- 26160833 TI - Development and Application of a High-Throughput Screening Method to Evaluate Antifungal Activity against Trichophyton tonsurans. AB - There exist relatively few drug classes on the market to treat dermatophyte infections. This investigation was designed to develop and validate high throughput methodology for screening and confirmation of chemicals for activity against Trichophyton tonsurans. Growth characteristics were examined on two platforms (96- and 384-well) in three media at eight spore concentrations over a period of up to 120 h. Microspectrophotometry was used to automate plate reads. The 384-well platform was used to screen more than 7000 compounds from six chemical libraries. Z-scores for optical density relative to positive growth controls were used to flag compounds of interest and activity confirmed in separate assays. The final conditions selected for both screening and confirmation with minimum inhibitory concentration (MIC) determination were growth for 48 h at 32 degrees C in SabDex with 1 * 10(4) spores per reaction. Sensitivity and specificity averaged 99.2% (range, 95.2%-100%) and 99.8% (range, 99.1%-100%), respectively. MICs for known antifungals were similar to those reported by others using Clinical and Laboratory Standards Institute methods. Several novel compound classes were identified to have activity against T. tonsurans with potency comparable to known antifungals. A robust, reproducible assay is described that permits high-throughput screening in T. tonsurans. PMID- 26160834 TI - AKAP4 is a circulating biomarker for non-small cell lung cancer. AB - Cancer testis antigens (CTAs) are widely expressed in tumor tissues, circulating tumor cells (CTCs) and in cancer derived exosomes that are frequently engulfed by lymphoid cells. To determine whether tumor derived CTA mRNAs could be detected in RNA from purified peripheral blood mononuclear cells (PBMC) of non-small cell lung cancer (NSCLC) patients, we assayed for the expression of 116 CTAs in PBMC RNA in a discovery set and identified AKAP4 as a potential NSCLC biomarker. We validated AKAP4 as a highly accurate biomarker in a cohort of 264 NSCLCs and 135 controls from 2 different sites including a subset of controls with high risk lung nodules. When all (264) lung cancers were compared with all (135) controls the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers are compared with all controls the AUC is 0.9795 and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules, a comparison of significant clinical importance, the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage, but independent of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer. PMID- 26160835 TI - RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy. AB - Inactivation of the retinoblastoma (RB1) tumor suppressor is one of the most frequent and early recognized molecular hallmarks of cancer. RB1, although mainly studied for its role in the regulation of cell cycle, emerged as a key regulator of many biological processes. Among these, RB1 has been implicated in the regulation of apoptosis, the alteration of which underlies both cancer development and resistance to therapy. RB1 role in apoptosis, however, is still controversial because, depending on the context, the apoptotic cues, and its own status, RB1 can act either by inhibiting or promoting apoptosis. Moreover, the mechanisms whereby RB1 controls both proliferation and apoptosis in a coordinated manner are only now beginning to be unraveled. Here, by reviewing the main studies assessing the effect of RB1 status and modulation on these processes, we provide an overview of the possible underlying molecular mechanisms whereby RB1, and its family members, dictate cell fate in various contexts. We also describe the current antitumoral strategies aimed at the use of RB1 as predictive, prognostic and therapeutic target in cancer. A thorough understanding of RB1 function in controlling cell fate determination is crucial for a successful translation of RB1 status assessment in the clinical setting. PMID- 26160837 TI - Long non-coding RNA AOC4P suppresses hepatocellular carcinoma metastasis by enhancing vimentin degradation and inhibiting epithelial-mesenchymal transition. AB - Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and cancer progression. However, the function of lncRNAs in the progression of hepatocellular carcinoma (HCC) remains largely unknown. We performed a comprehensive microarray analysis of lncRNA expression in human HCC samples. After validation in 108 HCC specimens, we identified a differentially expressed novel tumor suppressive lncRNA termed amine oxidase, copper containing 4, pseudogene (AOC4P). The level of AOC4P expression was significantly downregulated in 68% of HCC samples and negatively correlated with advanced clinical stage, capsule invasion and vessel invasion. Low AOC4P expression correlated with poor prognostic outcomes, serving as an independent prognostic factor for HCC. In vitro functional assays indicated that AOC4P overexpression significantly reduced cell proliferation, migration and invasion by inhibiting the epithelial mesenchymal transition (EMT). RNA immunoprecipitation assays demonstrated that AOC4P binds to vimentin and promotes its degradation. Animal model experiments confirmed the ability of AOC4P to suppress tumor growth and metastasis. Taken together, our findings suggest that AOC4P lncRNA acts as an HCC tumor suppressor by enhancing vimentin degradation and suppressing the EMT. By clarifying the mechanisms underlying HCC progression, these findings promote the development of novel therapeutic strategies for HCC. PMID- 26160836 TI - Putative effectors for prognosis in lung adenocarcinoma are ethnic and gender specific. AB - Lung adenocarcinoma possesses distinct patterns of EGFR/KRAS mutations between East Asian and Western, male and female patients. However, beyond the well-known EGFR/KRAS distinction, gender and ethnic specific molecular aberrations and their effects on prognosis remain largely unexplored. Association modules capture the dependency of an effector molecular aberration and target gene expressions. We established association modules from the copy number variation (CNV), DNA methylation and mRNA expression data of a Taiwanese female cohort. The inferred modules were validated in four external datasets of East Asian and Caucasian patients by examining the coherence of the target gene expressions and their associations with prognostic outcomes. Modules 1 (cis-acting effects with chromosome 7 CNV) and 3 (DNA methylations of UBIAD1 and VAV1) possessed significantly negative associations with survival times among two East Asian patient cohorts. Module 2 (cis-acting effects with chromosome 18 CNV) possessed significantly negative associations with survival times among the East Asian female subpopulation alone. By examining the genomic locations and functions of the target genes, we identified several putative effectors of the two cis-acting CNV modules: RAC1, EGFR, CDK5 and RALBP1. Furthermore, module 3 targets were enriched with genes involved in cell proliferation and division and hence were consistent with the negative associations with survival times. We demonstrated that association modules in lung adenocarcinoma with significant links of prognostic outcomes were ethnic and/or gender specific. This discovery has profound implications in diagnosis and treatment of lung adenocarcinoma and echoes the fundamental principles of the personalized medicine paradigm. PMID- 26160838 TI - Long non-coding RNA UCA1 induces non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway in EGFR-mutant non-small cell lung cancer. AB - The aim of this study was to explore the role of long non-coding RNA UCA1 (urothelial cancer-associated 1) in acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). In our study, UCA1 expression was significantly increased in lung cancer cells and patients with acquired resistance to EGFR TKIs. Over-expression of UCA1 was significantly associated with a shorter progression-free survival (PFS) [13.0 vs. 8.5 months, P < 0.01] in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (10.5 vs. 12.0 months, P = 0.778), but in patients with non T790M (19.0 vs. 9.0 months, P = 0.023). UCA1 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the AKT/mTOR pathway and epithelial-mesenchymal transition (EMT). The mTOR inhibitor was effective in UCA1-expressing cell PC9/R. Inhibiting mTOR could change the expression of UCA1, although there was no significant difference. In conclusion, the influence of over-expression of UCA1 on PFS for patients with acquired resistance to EGFR-TKIs was from the subgroup with non T790M mutation. UCA1 may induce non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway and EMT. PMID- 26160839 TI - Halofuginone inhibits colorectal cancer growth through suppression of Akt/mTORC1 signaling and glucose metabolism. AB - The Akt/mTORC1 pathway plays a central role in the activation of Warburg effect in cancer. Here, we present for the first time that halofuginone (HF) treatment inhibits colorectal cancer (CRC) growth both in vitro and in vivo through regulation of Akt/mTORC1 signaling pathway. Halofuginone treatment of human CRC cells inhibited cell proliferation, induced the generation of reactive oxygen species and apoptosis. As expected, reduced level of NADPH was also observed, at least in part due to inactivation of glucose-6-phosphate dehydrogenase in pentose phosphate pathway upon HF treatment. Given these findings, we further investigated metabolic regulation of HF through Akt/mTORC1-mediated aerobic glycolysis and found that HF downregulated Akt/mTORC1 signaling pathway. Moreover, metabolomics delineated the slower rates in both glycolytic flux and glucose-derived tricarboxylic acid cycle flux. Meanwhile, both glucose transporter GLUT1 and hexokinase-2 in glycolysis were suppressed in CRC cells upon HF treatment, to support our notion that HF regulates Akt/mTORC1 signaling pathway to dampen glucose uptake and glycolysis in CRC cells. Furthermore, HF retarded tumor growth in nude mice inoculated with HCT116 cells, showing the anticancer activity of HF through metabolic regulation of Akt/mTORC1 in CRC. PMID- 26160840 TI - Androgen receptor splice variants circumvent AR blockade by microtubule-targeting agents. AB - Docetaxel-based chemotherapy is established as a first-line treatment and standard of care for patients with metastatic castration-resistant prostate cancer. However, half of the patients do not respond to treatment and those do respond eventually become refractory. A better understanding of the resistance mechanisms to taxane chemotherapy is both urgent and clinical significant, as taxanes (docetaxel and cabazitaxel) are being used in various clinical settings. Sustained signaling through the androgen receptor (AR) has been established as a hallmark of CRPC. Recently, splicing variants of AR (AR-Vs) that lack the ligand binding domain (LBD) have been identified. These variants are constitutively active and drive prostate cancer growth in a castration-resistant manner. In taxane-resistant cell lines, we found the expression of a major variant, AR-V7, was upregulated. Furthermore, ectopic expression of two clinically relevant AR-Vs (AR-V7 and ARV567es), but not the full-length AR (AR-FL), reduced the sensitivities to taxanes in LNCaP cells. Treatment with taxanes inhibited the transcriptional activity of AR-FL, but not those of AR-Vs. This could be explained, at least in part, due to the inability of taxanes to block the nuclear translocation of AR-Vs. Through a series of deletion constructs, the microtubule binding activity was mapped to the LBD of AR. Finally, taxane-induced cytoplasm sequestration of AR-FL was alleviated when AR-Vs were present. These findings provide evidence that constitutively active AR-Vs maintain the AR signaling axis by evading the inhibitory effects of microtubule-targeting agents, suggesting that these AR-Vs play a role in resistance to taxane chemotherapy. PMID- 26160841 TI - Inhibition of miR-21 restores RANKL/OPG ratio in multiple myeloma-derived bone marrow stromal cells and impairs the resorbing activity of mature osteoclasts. AB - miR-21 is an oncogenic microRNA (miRNA) with an emerging role as therapeutic target in human malignancies, including multiple myeloma (MM). Here we investigated whether miR-21 is involved in MM-related bone disease (BD). We found that miR-21 expression is dramatically enhanced, while osteoprotegerin (OPG) is strongly reduced, in bone marrow stromal cells (BMSCs) adherent to MM cells. On this basis, we validated the 3'UTR of OPG mRNA as miR-21 target. Constitutive miR 21 inhibition in lentiviral-transduced BMSCs adherent to MM cells restored OPG expression and secretion. Interestingly, miR-21 inhibition reduced RANKL production by BMSCs. Overexpression of protein inhibitor of activated STAT3 (PIAS3), which is a direct and validated target of miR-21, antagonized STAT3 mediated RANKL gene activation. Finally, we demonstrate that constitutive expression of miR-21 inhibitors in BMSCs restores RANKL/OPG balance and dramatically impairs the resorbing activity of mature osteoclasts. Taken together, our data provide proof-of-concept that miR-21 overexpression within MM microenviroment plays a crucial role in bone resorption/apposition balance, supporting the design of innovative miR-21 inhibition-based strategies for MM related BD. PMID- 26160842 TI - ALDH1A1-overexpressing cells are differentiated cells but not cancer stem or progenitor cells in human hepatocellular carcinoma. AB - Aldehyde dehydrogenase 1A1 (ALDH1A1) is considered to be a cancer stem cell marker in several human malignancies. However, the role of ALDH1A1 in hepatocellular carcinoma (HCC) has not been well elucidated. In this study, we investigated the relationship between ALDH1A1 and clinicopathological findings and examined whether ALDH1A1 deserves to be a cancer stem cell marker in HCC. Sixty HCC samples obtained from surgical resection were collected for immunohistochemical (IHC) staining. Of these 60 samples, 47 samples of HCC tumorous and non-tumorous tissues were evaluated with qRT-PCR. There was no significant difference in the ALDH1A1-mRNA level between tumorous and non tumorous tissues. Tumorous ALDH1A1-mRNA level had no relationship with the clinicopathological features. Immunoreactivity of ALDH1A1 was classified into two groups based on the percentage of ALDH1A1-overexpressing cells. The ALDH1A1-high group was significantly associated with low serum levels of alpha-fetoprotein, small tumor diameter, very little lymphovascular invasion, more differentiated pathology and good stage. The ALDH1A1-high group showed more favorable prognosis for recurrence-free survival. In double-staining IHC, ALDH1A1 was not co expressed with BMI1, EpCAM, CD13, CD24, CD90 and CD133, which reported as cancer stem cell markers in HCC. In conclusion, ALDH1A1-overexpressing cells could appear to be differentiated cells rather than cancer stem cells in HCC. PMID- 26160843 TI - Lovastatin overcomes gefitinib resistance through TNF-alpha signaling in human cholangiocarcinomas with different LKB1 statuses in vitro and in vivo. AB - Gefitinib resistance has been shown to complicate cancer therapy. Lovastatin is a proteasome inhibitor that enhances gefitinib-induced antiproliferation in non small cell lung cancer. The objective of this study is to investigate the mechanism of lovastatin-induced antiproliferation in gefitinib-resistant human cholangiocarcinoma.Two gefitinib-resistant cholangiocarcinoma cell lines, SSP-25 and HuH-28, were used in this study to determine how to compensate gefitinib resistance. The combined effect of these two drugs was examined using the MTT assay, qPCR, immunoblotting, flow cytometry, and in vivo xenograft. Results indicated that lovastatin enhanced TNF-alpha-induced cell death in vitro. In addition, the combination of lovastatin with gefitinib enhanced accumulation of TNF-alpha. Furthermore, the treatment induced a synergistic cytotoxic effect and antiproliferation through apoptosis in SSP-25 cells and cell cycle arrest in HuH 28 cells. Reproductive results were also observed in in vivo xenografts. These observations suggest that the combination of gefitinib and lovastatin might have additive antiproliferative effects against gefitinib-resistant cholangiocarcinoma cells. Based on these observations, we concluded that the combination of gefitinib and lovastatin could be used to overcome gefitinib resistance in cholangiocarcinoma cells. PMID- 26160844 TI - Chemically modified, non-anticoagulant heparin derivatives are potent galectin-3 binding inhibitors and inhibit circulating galectin-3-promoted metastasis. AB - Concentrations of circulating galectin-3, a metastasis promoter, are greatly increased in cancer patients. Here we show that 2- or 6-de-O-sulfated, N acetylated heparin derivatives are galectin-3 binding inhibitors. These chemically modified heparin derivatives inhibited galectin-3-ligand binding and abolished galectin-3-mediated cancer cell-endothelial adhesion and angiogenesis. Unlike standard heparin, these modified heparin derivatives and their ultra-low molecular weight sub-fractions had neither anticoagulant activity nor effects on E-, L- or P-selectin binding to their ligands nor detectable cytotoxicity. Intravenous injection of such heparin derivatives (with cancer cells pre-treated with galectin-3 followed by 3 subcutaneous injections of the derivatives) abolished the circulating galectin-3-mediated increase in lung metastasis of human melanoma and colon cancer cells in nude mice. Structural analysis using nuclear magnetic resonance and synchrotron radiation circular dichroism spectroscopies showed that the modified heparin derivatives bind to the galectin 3 carbohydrate-recognition domain. Thus, these chemically modified, non anticoagulant, low-sulfated heparin derivatives are potent galectin-3 binding inhibitors with substantial potential as anti-metastasis/cancer drugs. PMID- 26160845 TI - Inhibition of ERRalpha suppresses epithelial mesenchymal transition of triple negative breast cancer cells by directly targeting fibronectin. AB - Triple-negative breast cancer (TNBC) patients have poor prognosis due to the aggressive metastatic behaviors. Our study reveals that expression of estrogen related receptor alpha (ERRalpha) is significantly (p < 0.01) positively associated with high grade tumors and lymph node metastasis, while negatively correlated with overall survival (OS), in 138 TNBC patients. Targeted inhibition of ERRalpha by its inverse agonist XCT-790 or si-RNA obviously inhibits in vitro motility of TNBC cells. While over expression of ERRalpha triggers the invasion and migration of TNBC cells. Further, si-ERRalpha and XCT-790 inhibit the epithelial mesenchymal transition (EMT) of TNBC cells with increasing the expression of E-cadherin and decreasing fibronectin (FN) and vimentin. While XCT 790 has no effect on the expression of EMT related transcription factors such as Snail or Slug. Further, inhibitors of MAPK, PI3K/Akt, NF-kappaB signal molecules, which are activated by XCT-790, can not attenuate the suppression effects of XCT 790 on EMT. Alternatively, luciferase reporter gene assays and ChIP analysis indicate that ERRalpha can directly bind with FN promoter at ERR response element 3 (ERRE-1), ERRE-3, and ERRE-4, while XCT-790 reduces this bond. In vivo data show that ERRalpha expression is significantly (p < 0.05) correlated with FN in clinical TNBC patients. In MDA-MB-231 tumor xenograft models, XCT-790 decreases the expression of FN, inhibits the growth and lung metastasis, and suppresses the EMT. Our results demonstrate that ERRalpha functions as a metastasis stimulator and its targeted inhibition may be a new therapeutic strategy for TNBC treatment. PMID- 26160846 TI - Implications for determining the optimal treatment for locally advanced rectal cancer in elderly patients aged 75 years and older. AB - Patients were excluded if they were older than 75 years of age in most clinical trials. Thus, the optimal treatment strategies in elderly patients with locally advanced rectal cancer (LARC) are still controversial. We designed our study to specifically evaluate the cancer specific survival of four subgroups of patients according to four different treatment modalities: surgery only, radiation (RT) only, neoadjuvant RT and adjuvant RT by analyzing the Surveillance, Epidemiology, and End Results (SEER)-registered database. The results showed that the 5-year cancer specific survival (CSS) was 52.1% in surgery only, 27.7% in RT only, 70.4% in neoadjuvant RT and 60.4% in adjuvant RT, which had significant difference in univariate log-rank test (P < 0.001) and multivariate Cox regression (P < 0.001). Thus, the neoadjuvant RT and surgery may be the optimal treatment pattern in elderly patients, especially for patients who are medically fit for the operation. PMID- 26160847 TI - Expression of high affinity folate receptor in breast cancer brain metastasis. AB - High affinity folate receptor (HFR) can be overexpressed in breast cancer and is associated with poor prognosis, however the expression in breast cancer brain metastases (BCBM) is unknown. The aim of this study was to analyze the rate of HFR expression in BCBM and its role in the prognosis of this high-risk cohort. We analyzed 19 brain metastasis (BM) and 13 primary tumors (PT) from a total of 25 patients. HFR status was assessed by immunohistochemistry. Median follow-up was 4.2 years (range 0.6-18.5). HFR was positive in 4/19 BM (21.1%) and in 1/13 PT (7.7%). Positive samples had low H-scores (range 1-50). 56% of patients had apocrine differentiation. OS was similar between patients with positive HFR (median OS 48 months) and negative HFR (median OS 69 months) (P = 0.25); and between patients with apocrine differentiation (median OS 63 months) and those without apocrine differentiation (median OS 69 months) (P = 0.49). To the best of our knowledge, this is the first analysis of HFR expression in BCBM. While previous studies associated the presence of HFR with worse prognosis; in our cohort HFR was positive in only 21.1% of BM with low levels of positivity. Neither HFR nor apocrine features had impact in OS. PMID- 26160849 TI - Neutrophils in viral infections: Current concepts and caveats. AB - Neutrophils are the first immune cell population recruited to sites of infection, including viral infections, and exhibit both protective and pathologic functions. In antibacterial and antifungal immunity, the role of neutrophils is well defined. However, in antiviral immunity, much less is known. Conventional wisdom suggests that neutrophils enhance antiviral defenses, yet evidence for that is limited. Interaction with other immune cell populations, virus internalization and killing, the release of cytokines, chemokines, and antimicrobial components are all mechanisms by which neutrophils can contribute to pathogen clearance. NET formation, extensively studied during bacterial infection, can further mediate antiviral defense by trapping and inactivating virus. In the present review, we discuss the current understanding of the complex role of neutrophil immunity in viral infections and disease pathogenesis and the potential mechanisms identified to date. We pinpoint the importance of a finely tuned neutrophilic response for achieving effective immune protection while avoiding detrimental tissue damage that can form the basis for the development of novel therapeutics. PMID- 26160850 TI - A Cys-Gly-Cys triad in the dehydrogenase region of Nox2 plays a key role in the interaction with p67phox. AB - p67(phox) is the paramount cytosolic regulator of the superoxide-generating Nox of phagocytes, by controlling the conformation of the catalytic component, Nox2. The initiating event of this process is a protein-protein interaction between p67(phox) and the part of Nox2 protruding into the cytosol, known as the dehydrogenase region. The aim of this study was to identify and characterize region(s) in Nox2 acting as binding site(s) for p67(phox). For this purpose, we measured the binding of recombinant p67(phox) to an array of 91 overlapping synthetic pentadecapeptides covering the length of the dehydrogenase region (residues 288-570). We found that: 1) p67(phox) binds to a site corresponding to residues 357-383, represented by a cluster of 5 peptides (Nos. 24-28); 2) maximal binding was to peptides 24 (357-371) and 28 (369-383); 3) these shared a (369)Cys Gly-Cys(371) triad, found to be responsible for binding; 4) the Cys-Gly-Cys triad was present in Nox2 of mammals, birds, and amphibians but was absent in other Nox; 5) substituting a Nox4 or Nox1 sequence for the Nox2 sequence in peptide 24 abolished binding; 6) replacing (369)Cys by Arg in peptide 24 (mimicking a mutation in chronic granulomatous disease) abolished binding; 7) the same replacement in peptide 28 did not affect binding, indicating the existence of an additional binding site. Our results reveal an essential role for the Cys-Gly-Cys triad in Nox2 in binding p67(phox), seconded by an additional binding region, comprising residues C terminal to Cys-Gly-Cys. The 2 regions interact with distinct partner sites in p67(phox). PMID- 26160848 TI - ErbB-3 activation by NRG-1beta sustains growth and promotes vemurafenib resistance in BRAF-V600E colon cancer stem cells (CSCs). AB - Approximately 5-10% of metastatic colorectal cancers harbor a BRAF-V600E mutation, which is correlated with resistance to EGFR-targeted therapies and worse clinical outcome. Vice versa, targeted inhibition of BRAF-V600E with the selective inhibitor PLX 4032 (Vemurafenib) is severely limited due to feedback re activation of EGFR in these tumors. Mounting evidence indicates that upregulation of the ErbB-3 signaling axis may occur in response to several targeted therapeutics, including Vemurafenib, and NRG-1beta-dependent re-activation of the PI3K/AKT survival pathway has been associated with therapy resistance.Here we show that colon CSCs express, next to EGFR and ErbB-2, also significant amounts of ErbB-3 on their membrane. This expression is functional as NRG-1beta strongly induces AKT/PKB and ERK phosphorylation, cell proliferation, clonogenic growth and promotes resistance to Vemurafenib in BRAF-V600E mutant colon CSCs. This resistance was completely dependent on ErbB-3 expression, as evidenced by knockdown of ErbB-3. More importantly, resistance could be alleviated with therapeutic antibody blocking ErbB-3 activation, which impaired NRG-1beta-driven AKT/PKB and ERK activation, clonogenic growth in vitro and tumor growth in xenograft models. In conclusion, our findings suggest that targeting ErbB-3 receptors could represent an effective therapeutic approach in BRAF-V600E mutant colon cancer. PMID- 26160851 TI - Neurobrucellosis: an often forgotten cause of chronic meningitis. AB - We report a 26-year-old man of neurobrucellosis who presented with intermittent fever and headache for 2 years, sensori-neural hearing loss with cerebellar ataxia. He responded well to a combination of antimicrobials with significant clinical improvement. PMID- 26160852 TI - radir package: an R implementation for cytogenetic biodosimetry dose estimation. AB - The Bayesian framework has been shown to be very useful in cytogenetic dose estimation. This approach allows description of the probability of an event in terms of previous knowledge, e.g. its expectation and/or its uncertainty. A new R package entitled radir (radiation inverse regression) has been implemented with the aim of reproducing a recent Bayesian-type dose estimation methodology. radir adopts the method of dose estimation under the Poisson assumption of the responses (the chromosomal aberrations counts) for the required dose-response curve (typically linear or quadratic). The individual commands are described in detail and relevant examples of the use of the methods and the corresponding radir software tools are given. The suitability of this methodology is highlighted and its application encouraged by providing a user-friendly command type software interface within the R statistical software (version 3.1.1 or higher), which includes a complete manual. PMID- 26160854 TI - A reverse dorsoradial pedicled flap from the thumb for a soft tissue defect in the finger. PMID- 26160853 TI - Adult Bone Marrow Cell Therapy for Ischemic Heart Disease: Evidence and Insights From Randomized Controlled Trials. AB - RATIONALE: Notwithstanding the uncertainties about the outcomes of bone marrow cell (BMC) therapy for heart repair, further insights are critically needed to improve this promising approach. OBJECTIVE: To delineate the true effect of BMC therapy for cardiac repair and gain insights for future trials through systematic review and meta-analysis of data from eligible randomized controlled trials. METHODS AND RESULTS: Database searches through August 2014 identified 48 eligible randomized controlled trials (enrolling 2602 patients). Weighted mean differences for changes in left ventricular (LV) ejection fraction, infarct size, LV end systolic volume, and LV end-diastolic volume were analyzed with random-effects meta-analysis. Compared with standard therapy, BMC transplantation improved LV ejection fraction (2.92%; 95% confidence interval, 1.91-3.92; P<0.00001), reduced infarct size (-2.25%; 95% confidence interval, -3.55 to -0.95; P=0.0007) and LV end-systolic volume (-6.37 mL; 95% confidence interval, -8.95 to -3.80; P<0.00001), and tended to reduce LV end-diastolic volume (-2.26 mL; 95% confidence interval, -4.59 to 0.07; P=0.06). Similar effects were noted when data were analyzed after excluding studies with discrepancies in reporting of outcomes. The benefits also persisted when cardiac catheterization was performed in control patients as well. Although imaging modalities partly influenced the outcomes, LV ejection fraction improved in BMC-treated patients when assessed by magnetic resonance imaging. Early (<48 hours) BMC injection after myocardial Infarction was more effective in reducing infarct size, whereas BMC injection between 3 and 10 days proved superior toward improving systolic function. A minimum of 50 million BMCs seemed to be necessary, with limited additional benefits seen with increasing cell numbers. BMC therapy was safe and improved clinical outcomes, including all-cause mortality, recurrent myocardial Infarction, ventricular arrhythmia, and cerebrovascular accident during follow up, albeit with differences between acute myocardial Infarction and chronic ischemic heart disease subgroups. CONCLUSIONS: Transplantation of adult BMCs improves LV ejection fraction, reduces infarct size, and ameliorates remodeling in patients with ischemic heart disease. These effects are upheld in the analyses of studies using magnetic resonance imaging and also after excluding studies with discrepant reporting of outcomes. BMC transplantation may also reduce the incidence of death, recurrent myocardial Infarction, ventricular arrhythmia, and cerebrovascular accident during follow-up. PMID- 26160855 TI - HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth. AB - The reduced diameter of skeletal myofibres is a hallmark of several congenital myopathies, yet the underlying cellular and molecular mechanisms remain elusive. In this study, we investigate the role of HACD1/PTPLA, which is involved in the elongation of the very long chain fatty acids, in muscle fibre formation. In humans and dogs, HACD1 deficiency leads to a congenital myopathy with fibre size disproportion associated with a generalized muscle weakness. Through analysis of HACD1-deficient Labradors, Hacd1-knockout mice, and Hacd1-deficient myoblasts, we provide evidence that HACD1 promotes myoblast fusion during muscle development and regeneration. We further demonstrate that in normal differentiating myoblasts, expression of the catalytically active HACD1 isoform, which is encoded by a muscle-enriched splice variant, yields decreased lysophosphatidylcholine content, a potent inhibitor of myoblast fusion, and increased concentrations of >= C18 and monounsaturated fatty acids of phospholipids. These lipid modifications correlate with a reduction in plasma membrane rigidity. In conclusion, we propose that fusion impairment constitutes a novel, non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism. PMID- 26160856 TI - A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair. AB - BACKGROUND: Woolly hair (WH) is a hair abnormality that is primarily characterised by tightly curled hair with abnormal growth. METHODS: In two unrelated consanguineous Pakistani families with non-syndromic autosomal recessive (AR) WH, homozygosity mapping and linkage analysis identified a locus within 17q21.1-q22, which contains the type I keratin gene cluster. A DNA sample from an affected individual from each family underwent exome sequencing. RESULTS: A homozygous missense variant c.950T>C (p.(Leu317Pro)) within KRT25 segregated with ARWH in both families, and has a combined maximum two-point LOD score of 7.9 at Theta=0. The KRT25 variant is predicted to result in disruption of the second alpha-helical rod domain and the entire protein structure, thus possibly interfering with heterodimerisation of K25 with type II keratins within the inner root sheath (IRS) of the hair follicle and the medulla of the hair shaft. CONCLUSIONS: Our findings implicate a novel gene involved in human hair abnormality, and are consistent with the curled, fragile hair found in mice with Krt25 mutations, and further support the role of IRS-specific type I keratins in hair follicle development and maintenance of hair texture. PMID- 26160857 TI - Development of a Dating Violence Assessment Tool for Late Adolescence Across Three Countries: The Violence in Adolescents' Dating Relationships Inventory (VADRI). AB - Accurate assessment of dating violence (DV) is crucial for evaluation and intervention planning. However, extant self-report measurement tools of DV do not adequately consider age-, generation-, and culture-specific issues, which are essential for its accurate conceptualization. To address these gaps, we developed the Violence in Adolescents' Dating Relationships Inventory (VADRI) and evaluated its psychometric properties. The VADRI was developed based on a qualitative approach for item development through adolescents' individual interviews, focus groups, and experts' judgments, followed by a quantitative approach for tool assessment. Two aspects of DV were addressed: victimization and perpetration. After the necessary cultural and linguistic adaptation of items, the instrument was administered to 466 adolescents from three Spanish-speaking countries: Guatemala, Mexico, and Spain. The items were best represented by a one-factor solution in each country, which suggests that DV is a unidimensional construct combining victimization and perpetration. Analyses of item-level factor weights and differential item functioning were conducted aimed at obtaining information about items that best represented the construct, resulting in a 26-item final version that was cross-culturally equivalent. Convergent validity was supported by positive correlations with the Conflict in Adolescent Dating Relationships Inventory, and reliability analyses yielded favorable results (with all Cronbach's alpha values above .90). We conclude that the VADRI is a valid and reliable instrument for the assessment of DV in various cultural contexts. PMID- 26160858 TI - Survival of the Fittest and the Sexiest: Evolutionary Origins of Adolescent Bullying. AB - The central idea of evolutionary psychology theory (EPT) is that species evolve to carry or exhibit certain traits/behaviors because these characteristics increase their ability to survive and reproduce. Proponents of EPT propose that bullying emerges from evolutionary development, providing an adaptive edge for gaining better sexual opportunities and physical protection, and promoting mental health. This study examines adolescent bullying behaviors via the lens of EPT. Questionnaires were administered to 135 adolescents, ages 13 to 16, from one secondary school in metro Vancouver, British Columbia. Participants were categorized into one of four groups (bullies, victims, bully/victims, or bystanders) according to their involvement in bullying interactions as measured by the Olweus Bully/Victim Questionnaire. Four dependent variables were examined: depression, self-esteem, social status, and social anxiety. Results indicate that bullies had the most positive scores on mental health measures and held the highest social rank in the school environment, with significant differences limited to comparisons between bullies and bully/victims. These results lend support to the hypothesis that youth bullying is derived from evolutionary development. Implications for approaching anti-bullying strategies in schools and directions for future studies are discussed. PMID- 26160859 TI - Arrhythmic Mitral Valve Prolapse and Sudden Cardiac Death. AB - BACKGROUND: Mitral valve prolapse (MVP) may present with ventricular arrhythmias and sudden cardiac death (SCD) even in the absence of hemodynamic impairment. The structural basis of ventricular electric instability remains elusive. METHODS AND RESULTS: The cardiac pathology registry of 650 young adults (<=40 years of age) with SCD was reviewed, and cases with MVP as the only cause of SCD were re examined. Forty-three patients with MVP (26 females; age range, 19-40 years; median, 32 years) were identified (7% of all SCD, 13% of women). Among 12 cases with available ECG, 10 (83%) had inverted T waves on inferior leads, and all had right bundle-branch block ventricular arrhythmias. A bileaflet involvement was found in 70%. Left ventricular fibrosis was detected at histology at the level of papillary muscles in all patients, and inferobasal wall in 88%. Living patients with MVP with (n=30) and without (control subjects; n=14) complex ventricular arrhythmias underwent a study protocol including contrast-enhanced cardiac magnetic resonance. Patients with either right bundle-branch block type or polymorphic complex ventricular arrhythmias (22 females; age range, 28-43 years; median, 41 years), showed a bileaflet involvement in 70% of cases. Left ventricular late enhancement was identified by contrast-enhanced cardiac magnetic resonance in 93% of patients versus 14% of control subjects (P<0.001), with a regional distribution overlapping the histopathology findings in SCD cases. CONCLUSIONS: MVP is an underestimated cause of arrhythmic SCD, mostly in young adult women. Fibrosis of the papillary muscles and inferobasal left ventricular wall, suggesting a myocardial stretch by the prolapsing leaflet, is the structural hallmark and correlates with ventricular arrhythmias origin. Contrast enhanced cardiac magnetic resonance may help to identify in vivo this concealed substrate for risk stratification. PMID- 26160860 TI - The Knot That Binds Mitral Valve Prolapse and Sudden Cardiac Death. PMID- 26160861 TI - Radiation safety during remediation of the SevRAO facilities: 10 years of regulatory experience. AB - In compliance with the fundamentals of the government's policy in the field of nuclear and radiation safety approved by the President of the Russian Federation, Russia has developed a national program for decommissioning of its nuclear legacy. Under this program, the State Atomic Energy Corporation 'Rosatom' is carrying out remediation of a Site for Temporary Storage of spent nuclear fuel (SNF) and radioactive waste (RW) at Andreeva Bay located in Northwest Russia. The short term plan includes implementation of the most critical stage of remediation, which involves the recovery of SNF from what have historically been poorly maintained storage facilities. SNF and RW are stored in non-standard conditions in tanks designed in some cases for other purposes. It is planned to transport recovered SNF to PA 'Mayak' in the southern Urals. This article analyses the current state of the radiation safety supervision of workers and the public in terms of the regulatory preparedness to implement effective supervision of radiation safety during radiation-hazardous operations. It presents the results of long-term radiation monitoring, which serve as informative indicators of the effectiveness of the site remediation and describes the evolving radiation situation. The state of radiation protection and health care service support for emergency preparedness is characterized by the need to further study the issues of the regulator-operator interactions to prevent and mitigate consequences of a radiological accident at the facility. Having in mind the continuing intensification of practical management activities related to SNF and RW in the whole of northwest Russia, it is reasonable to coordinate the activities of the supervision bodies within a strategic master plan. Arrangements for this master plan are discussed, including a proposed programme of actions to enhance the regulatory supervision in order to support accelerated mitigation of threats related to the nuclear legacy in the area. PMID- 26160862 TI - Unlocking the Potential of High-Throughput Drug Combination Assays Using Acoustic Dispensing. AB - Assessment of synergistic effects of drug combinations in vitro is a critical part of anticancer drug research. However, the complexities of dosing and analyzing two drugs over the appropriate range of doses have generally led to compromises in experimental design that restrict the quality and robustness of the data. In particular, the use of a single dose response of combined drugs, rather than a full two-way matrix of varying doses, has predominated in higher throughput studies. Acoustic dispensing unlocks the potential of high-throughput dose matrix analysis. We have developed acoustic dispensing protocols that enable compound synergy assays in a 384-well format. This experimental design is considerably more efficient and flexible with respect to time, reagent usage, and labware than is achievable using traditional serial-dilution approaches. Data analysis tools integrated in Genedata Screener were used to efficiently deconvolute the combination compound mapping scheme and calculate compound potency and synergy metrics. We have applied this workflow to evaluate interactions among drugs targeting different nodes of the mitogen-activated protein kinase pathway in a panel of cancer cell lines. PMID- 26160863 TI - Electrochemical Study of AISI C1018 Steel in Methanesulfonic Acid Containing an Acetylenic Alcohol-Based Corrosion Inhibitor Formulation. AB - In this work, the electrochemical potentiodynamic behavior of AISI C1018 lower grade steel material was investigated in 20 wt.% methanesulfonic acid (MSA) solutions with or without different components to design corrosion inhibitor formulations based on acetylenic alcohol, cinnamaldehyde, 1-dodecylpyridinium chloride, and methanol. MSA has recently been considered as a new potential acid to be used in the matrix stimulation procedure and in well cleaning. It is demonstrated that AISI C1018 steel MSA needs to be inhibited. Inhibition type is determined for single components as well as for formulations. PMID- 26160864 TI - Association of short-term ozone and temperature with sleep disordered breathing. AB - Scarce evidence suggests that ambient air pollution and temperature might play a role in incidence and severity of sleep disordered breathing (SDB). We investigated the association of short-term exposure to fine particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 MUm (PM10)), ozone and temperature with SDB in the general population. Between 2006 and 2008, 1773 participants (aged 50-80 years) of the Heinz Nixdorf Recall study underwent screening for SDB, as defined by the apnoea-hypopnoea index (AHI). We assessed daily exposure to PM10, ozone, temperature and humidity. We used multiple linear regression to estimate associations of daily PM10, ozone levels and temperature on the day of screening, adjusting for relative humidity, season, age, sex, body mass index, education, smoking habits, alcohol consumption and physical activity. In the study population, the mean+/-sd AHI was 11.2+/-11.4 events.h(-1). Over all seasons, an interquartile range increase in temperature (8.6 degrees C) and ozone (39.5 ug.m(-3)) was associated with a 10.2% (95% CI 1.2-20.0%) and 10.1% (95% CI 2.0-18.9%) increase in AHI, respectively. Associations for temperature were stronger in summer, yielding a 32.4% (95% CI 0.0-75.3%) increase in AHI per 8.6 degrees C (p-value for season-temperature interaction 0.08). We observed that AHI was not associated with PM10. This study suggests that short-term variations in ozone concentration and temperature are associated with SDB. PMID- 26160865 TI - miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production. AB - Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis. IL-8 protein and mRNA were measured in cystic fibrosis and non-cystic fibrosis bronchoalveolar lavage fluid and bronchial brushings (n=20 per group). miRNAs decreased in the cystic fibrosis lung and predicted to target IL-8 mRNA were quantified in betaENaC-transgenic, cystic fibrosis transmembrane conductance regulator (Cftr)-/- and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosis versus non-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide, Pseudomonas-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured. miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, betaENaC-transgenic mice and bronchial epithelial cells chronically stimulated with Pseudomonas conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o(-) tracheal, CFBE41o( ) and/or IB3 bronchial epithelial cells. These results implicate defective CFTR, inflammation, neutrophilia and mucus overproduction in regulation of miR-17. Modulating miR-17 expression in cystic fibrosis bronchial epithelial cells may be a novel anti-inflammatory strategy for cystic fibrosis and other chronic inflammatory airway diseases. PMID- 26160866 TI - Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases. PMID- 26160867 TI - Blood stem cell transplantation to treat cystic lung light chain deposition disease. PMID- 26160868 TI - Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations. AB - Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response.A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering.Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI -0.60- -0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: -0.9%, 95% CI -1.0- -0.4%).LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1. PMID- 26160869 TI - Low plasma CC16 levels in smokers are associated with a higher risk for chronic bronchitis. PMID- 26160870 TI - Linezolid tolerability in multidrug-resistant tuberculosis: a retrospective study. PMID- 26160871 TI - Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands. AB - The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands. Using a Markov-type model, incremental cost effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65-74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted. The ICER for base-case was ?8650 per QALY (95% CI 5750-17,100). Vaccination of high-risk individuals aged 65-74 years was cost-saving and extension to medium risk individuals aged 65-74 years yielded an ICER of ?2900. Further extension to include medium- and high-risk individuals aged >=18 years yielded an ICER of ?3100.PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries. PMID- 26160872 TI - Increased alveolar soluble annexin V promotes lung inflammation and fibrosis. AB - The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesised that alveolar soluble annexin V contributes to lung fibrosis, based on the observation that human IPF bronchoalveolar lavage fluid (BALF) containing high annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when annexin V was depleted from the BALF. Conditioned medium from annexin V-treated alveolar epithelial type 2 cells (AEC2), but not annexin V per se, induced proliferation of human fibroblasts and contained pro-fibrotic, IPF-associated proteins, as well as pro-inflammatory cytokines that were found to correlate tightly (r>0.95) with annexin V levels in human BALF. ErbB2 receptor tyrosine kinase in AECs was activated by annexin V, and blockade reduced the fibrotic potential of annexin V-treated AEC-conditioned medium. In vivo, aerosol delivery of annexin V to mouse lung induced inflammation, fibrosis and increased hydroxyproline, with activation of Wnt, transforming growth factor-beta, mitogen-activated protein kinase and nuclear factor-kappaB signalling pathways, as seen in IPF. Chronically increased alveolar annexin V levels, as reflected in increased IPF BALF levels, may contribute to the progression of IPF by inducing the release of pro-fibrotic mediators. PMID- 26160873 TI - An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. AB - Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort.The "European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease" was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity.The task force proposes the term "interstitial pneumonia with autoimmune features" (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features.A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort. PMID- 26160874 TI - COPD comorbidities network. AB - Multimorbidity frequently affects the ageing population and their co-existence may not occur at random. Understanding their interactions and that with clinical variables could be important for disease screening and management.In a cohort of 1969 chronic obstructive pulmonary disease (COPD) patients and 316 non-COPD controls, we applied a network-based analysis to explore the associations between multiple comorbidities. Clinical characteristics (age, degree of obstruction, walking, dyspnoea, body mass index) and 79 comorbidities were identified and their interrelationships quantified. Using network visualisation software, we represented each clinical variable and comorbidity as a node with linkages representing statistically significant associations.The resulting COPD comorbidity network had 428, 357 or 265 linkages depending on the statistical threshold used (p<=0.01, p<=0.001 or p<=0.0001). There were more nodes and links in COPD compared with controls after adjusting for age, sex and number of subjects. In COPD, a subset of nodes had a larger number of linkages representing hubs. Four sub-networks or modules were identified using an inter-linkage affinity algorithm and their display provided meaningful interactions not discernible by univariate analysis.COPD patients are affected by larger number of multiple interlinked morbidities which clustering pattern may suggest common pathobiological processes or be utilised for screening and/or therapeutic interventions. PMID- 26160875 TI - Simulator training for endobronchial ultrasound: a randomised controlled trial. AB - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is very operator dependent and has a long learning curve. Simulation-based training might shorten the learning curve, and an assessment tool with solid validity evidence could ensure basic competency before unsupervised performance.A total of 16 respiratory physicians, without EBUS experience, were randomised to either virtual-reality simulator training or traditional apprenticeship training on patients, and then each physician performed EBUS-TBNA procedures on three patients. Three blinded, independent assessor assessed the video recordings of the procedures using a newly developed EBUS assessment tool (EBUSAT).The internal consistency was high (Cronbach's alpha=0.95); the generalisability coefficient was good (0.86), and the tool had discriminatory ability (p<0.001). Procedures performed by simulator-trained novices were rated higher than procedures performed by apprenticeship-trained novices: mean+/-sd are 24.2+/-7.9 points and 20.2+/-9.4 points, respectively; p=0.006. A pass/fail standard of 28.9 points was established using the contrasting groups method, resulting in 16 (67%) and 20 (83%) procedures performed by simulator-trained novices and apprenticeship trained novices failing the test, respectively; p<0.001.The endobronchial ultrasound assessment tool could be used to provide reliable and valid assessment of competence in EBUS-TBNA, and act as an aid in certification. Virtual-reality simulator training was shown to be more effective than traditional apprenticeship training. PMID- 26160876 TI - Empiric definition of eligibility criteria for clinical trials in relapsed/refractory acute myeloid leukemia: analysis of 1,892 patients from HOVON/SAKK and SWOG. PMID- 26160877 TI - Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed up for 25 years. AB - Additional malignancies in multiple myeloma patients after first-line and maintenance treatment have been observed, questioning whether specific risks exist. Second primary malignancies have also gained attention since randomized data showed associations to newer drugs. We have conducted this large registry analysis in 744 consecutive patients and analyzed: 1) frequency and onset of additional malignancies; and 2) second primary malignancy- and myeloma-specific risks. We assessed the frequency of additional malignancies in terms of host-, myeloma- and treatment-specific characteristics. To compare these risks, we estimated cumulative incidence rates for second malignancies and myeloma with Fine and Gray regression models taking into account competing risks. Additional malignancies were found in 118 patients: prior or synchronous malignancies in 63% and subsequent in 37%. Cumulative incidence rates for second malignancies were increased in IgG-myeloma and decreased in bortezomib-treated patients (P<0.05). Cumulative incidence rates for myeloma death were increased with higher stage and age, but decreased in IgG-subtypes and due to anti-myeloma treatment (P<0.05). Cytogenetics in patients acquiring second primary malignancies were predominantly favorable, suggesting that indolent myeloma and long disease latency may allow the manifestation of additional malignancies. An assessment of the Surveillance, Epidemiology, and End Result Program of the National Cancer Institute and our data with long-term follow up of 25 years confirmed a prevalence of second malignancy of 10% at 25 years, whereas death from myeloma decreased from 90% to 83%, respectively. Our important findings widen our knowledge of second malignancies and show that they are of increasing relevance as the prognosis in myeloma improves and mortality rates decrease. PMID- 26160878 TI - Potential role of hypoxia in early stages of Hodgkin lymphoma pathogenesis. AB - A unique feature of the germinal center B cell-derived Hodgkin and Reed/Sternberg cells of classical Hodgkin lymphoma is their lost B cell phenotype and the aberrant expression of factors of other hematopoietic cell types, including ID2 and NOTCH1. As cellular dedifferentiation and upregulation of ID2 and NOTCH1 are typical consequences of a hypoxic response, we wondered whether hypoxia may impose an HRS cell-like phenotype in B cells. Culturing normal B cells or cell lines of germinal center-type diffuse large B-cell lymphoma under hypoxic conditions caused partial downregulation of several B cell markers, ID2 upregulation, and increased NOTCH1 activity. The hypoxic cells acquired further features of Hodgkin and Reed/Sternberg cells, including increased JUN expression, and enhanced NFkappaB activity. The Hodgkin and Reed/Sternberg cell-expressed epigenetic regulators KDM4C and PCGF2, as well as the phosphatase DUSP1 were partially induced in hypoxic B cells. Inhibition of DUSP1 was toxic for classical Hodgkin lymphoma cell lines. Thus, hypoxia induces key Hodgkin and Reed/Sternberg cell characteristics in mature B cells. We speculate that hypoxic conditions in the germinal center may impose phenotypic changes in germinal center B cells, promoting their survival and initiating their differentiation towards a Hodgkin and Reed/Sternberg cell-like phenotype. These may then be stabilized by transforming events in the Hodgkin and Reed/Sternberg precursor cells. PMID- 26160879 TI - Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. AB - Pomalidomide is a distinct oral IMiD((r)) immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (<= or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID- 26160880 TI - Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study. AB - This phase Ib/II trial combined the pan-deacetylase inhibitor panobinostat with chemotherapy followed by panobinostat maintenance in elderly patients with newly diagnosed acute myeloid leukemia. Patients with prior history of myelodysplastic syndrome were excluded and 38 evaluable patients were included in the study (median age: 71 years; range: 65-83). Study patients received an induction with idarubicin (8 mg/m(2) iv days 1-3) plus cytarabine (100 mg/m(2) iv days 1-7) plus panobinostat po at escalating doses (days 8, 10, 12, 15, 17 and 19) that could be repeated in non-responding patients. Patients achieving complete remission received a consolidation cycle with the same schema, followed by panobinostat maintenance (40 mg po 3 days/week) every other week until progression. Thirty-one patients were treated at the maximum tolerated dose of panobinostat in the combination (10 mg) with good tolerability. Complete remission rate was 64% with a time to relapse of 17.0 months (12.8-21.1). Median overall survival for the whole series was 17 months (5.5-28.4). Moreover, in 4 of 5 patients with persistent minimal residual disease before maintenance, panobinostat monotherapy reduced its levels, with complete negativization in two of them. Maintenance phase was well tolerated. The most frequent adverse events were thrombocytopenia (25% grades 3/4), and gastrointestinal toxicity, asthenia and anorexia (mainly grades 1/2). Five patients required dose reduction during this phase, but only one discontinued therapy due to toxicity. These results suggest that panobinostat is one of the first novel agents with activity in elderly acute myeloid leukemia patients, and suggest further investigation is warranted, particularly in the context of maintenance therapy. This trial is registered at clinicaltrials.gov identifier: 00840346. PMID- 26160881 TI - Interactions Between High- and Low-Risk HPV Types Reduce the Risk of Squamous Cervical Cancer. AB - BACKGROUND: The clinical significance of co-infections with high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in the etiology of cervical cancer is debated, as prospective evidence on this issue is limited. However, the question is of increasing relevance in relation to HPV-based cancer prevention. METHODS: In two population-based nested case-control studies among women participating in cervical screening with baseline normal smears, we collected 4659 smears from women who later developed cancer in situ (CIS; n = 524) or squamous cervical cancer (SCC; n = 378) and individually matched control subjects who remained free of disease during study follow-up. The median follow-up until diagnosis was 6.4 to 7.8 years. All smears were tested for HPV. We used conditional logistic regression models with two-way interaction terms to estimate relative risks (RRs) for CIS and SCC, respectively. All statistical tests were two-sided. RESULTS: Compared with women who were infected with HRHPV only, women who were also infected with LRHPV had a lower risk for SCC (RR = 0.2, 95% confidence interval [CI] = 0.04 to 0.99, P = .049). This interaction was not shown for CIS (RR = 1.1, 95% CI = 0.4 to 3.6). Women who were positive for both HRHPV and LRHPV had, on average, a 4.8 year longer time to diagnosis of SCC than women who were positive for HRHPV only (P = .006). Results were highly robust in sensitivity analyses. CONCLUSION: Co-infection with LRHPV is associated with a lower risk of future invasive disease and longer time to diagnosis than infection with HRHPV alone. We propose that co-infection with LRHPV interferes with the rate of progression to invasive cervical cancer. PMID- 26160883 TI - Participation in Cancer Pharmacogenomic Studies: A Study of 8456 Patients Registered to Clinical Trials in the Cancer and Leukemia Group B (Alliance). AB - BACKGROUND: Clinically annotated specimens from cancer clinical trial participants offer an opportunity for discovery and validation of pharmacogenomic findings. The purpose of this observational study is to better understand patient/institution factors that may contribute to participation in the pharmacogenomic component of prospective cancer clinical trials. METHODS: Patient demographic information (age, sex, self-reported race) and institutional characteristics (CALGB/CTSU site, "diversity," and accrual) were evaluated for 8456 patients enrolled in seven CALGB phase III studies with a pharmacogenomic component. All statistical tests were two-sided. RESULTS: The majority of patients (81%) consented to participate in the pharmacogenomic component. However, in a multivariable analysis, site (CALGB vs CTSU) and "institutional diversity" (percent minority cancer patients on national trials) were statistically significantly associated with participation. For both whites and nonwhites, patients from CALGB sites were more likely to participate compared with patients from CTSU sites (whites: odds ratio [OR] = 2.26, 95% confidence interval [CI] = 1.68 to 3.04, P < .001; nonwhites: OR = 1.79, 95% CI = 1.52 to 2.11, P < .001). However, as "institutional diversity" increased, the likelihood of participation in the pharmacogenomics component decreased for both white (OR = 0.94, 95% CI = 0.91 to 0.97, P < .001) and nonwhite patients (OR = 0.90, 95% CI = 0.81 to 1.00, P = .05). CONCLUSIONS: Most clinical trial cancer patients across geographical, racial, and practice settings are willing to participate in pharmacogenomic studies. However, to promote equitable benefit to the larger cancer community, optimization of both patient and institutional participation are needed. Institutional factors may be even more compelling than patient demographics. Prospective studies are needed to identify and address barriers/incentives to participation in pharmacogenomic research at the patient, clinician, and institutional levels. PMID- 26160882 TI - Racial Differences in BRAF/KRAS Mutation Rates and Survival in Stage III Colon Cancer Patients. AB - BACKGROUND: It is unknown if, after controlling for clinicopathologic variables and treatment, racial disparities in colon cancer outcomes persist. Molecular marker analysis in North American patients comparing Asians with other races has not been reported. METHODS: BRAF (V600E) and KRAS mutations were analyzed in node positive colon cancer patients (n = 3305) treated with FOLFOX-based chemotherapy in an adjuvant trial (Alliance N0147). Race categories included Asian, black, or white. Cox models were used to estimate disease-free survival (DFS) and time to recurrence (TTR). All statistical tests were two-sided. RESULTS: BRAF mutation frequency in tumors from whites (13.9%) was twice that of tumors from Asians or blacks. KRAS mutation rates were highest in tumors from blacks (44.1%). KRAS/BRAF wild-type tumors were most common among Asians (66.7%) (P overall < .001). The prognostic impact of race differed by age and N stage (both P interaction < .02). Compared with whites, blacks had shorter DFS among patients younger than age 50 years (hazard ratio [HR] = 2.84, 95% confidence interval [CI] = 1.73 to 4.66) or with N1 disease (HR = 1.54, 95% CI = 1.04 to 2.29), independent of BRAF, KRAS, and other covariates. Findings were consistent using TTR as the outcome. Asians had longer DFS among N2 tumors that was partly mediated by less frequent BRAF mutation. CONCLUSIONS: Colon cancers from Asians have a lower rate of BRAF and KRAS mutations than blacks or whites. We report a novel interaction of race with age and N stage in node-positive disease, indicating that racial disparities in survival persist despite uniform stage and treatment in a phase III trial. PMID- 26160885 TI - Count ratio model reveals bias affecting NGS fold changes. AB - Various biases affect high-throughput sequencing read counts. Contrary to the general assumption, we show that bias does not always cancel out when fold changes are computed and that bias affects more than 20% of genes that are called differentially regulated in RNA-seq experiments with drastic effects on subsequent biological interpretation. Here, we propose a novel approach to estimate fold changes. Our method is based on a probabilistic model that directly incorporates count ratios instead of read counts. It provides a theoretical foundation for pseudo-counts and can be used to estimate fold change credible intervals as well as normalization factors that outperform currently used normalization methods. We show that fold change estimates are significantly improved by our method by comparing RNA-seq derived fold changes to qPCR data from the MAQC/SEQC project as a reference and analyzing random barcoded sequencing data. Our software implementation is freely available from the project website http://www.bio.ifi.lmu.de/software/lfc. PMID- 26160884 TI - Shaping the landscape of the Escherichia coli chromosome: replication transcription encounters in cells with an ectopic replication origin. AB - Each cell division requires the unwinding of millions of DNA base pairs to allow chromosome duplication and gene transcription. As DNA replication and transcription share the same template, conflicts between both processes are unavoidable and head-on collisions are thought to be particularly problematic. Surprisingly, a recent study reported unperturbed cell cycle progression in Escherichia coli cells with an ectopic replication origin in which highly transcribed rrn operons were forced to be replicated opposite to normal. In this study we have re-generated a similar strain and found the doubling time to be twice that of normal cells. Replication profiles of this background revealed significant deviations in comparison to wild-type profiles, particularly in highly transcribed regions and the termination area. These deviations were alleviated by mutations that either inactivate the termination area or destabilise RNA polymerase complexes and allow their easier displacement by replication forks. Our data demonstrate that head-on replication-transcription conflicts are highly problematic. Indeed, analysis of the replication profile of the previously published E. coli construct revealed a chromosomal rearrangement that alleviates replication-transcription conflicts in an intriguingly simple way. Our data support the idea that avoiding head-on collisions has significantly contributed to shaping the distinct architecture of bacterial chromosomes. PMID- 26160888 TI - Crystal phase control in GaAs nanowires: opposing trends in the Ga- and As limited growth regimes. AB - Here we demonstrate the existence of two distinct regimes for tuning crystal structure in GaAs nanowires from zinc blende to wurtzite using a single process parameter: V/III-ratio, or variation of the group V precursor flow. Extensive previous studies have shown that crystal structure is sensitive to V/III-ratio, and even that it is possible to change structure entirely using this single parameter. However, an open question has remained about whether the observed dependencies are related to growth technique or types of precursors used. Specifically, opposite trends have been reported for molecular beam epitaxy (MBE) and metal organic vapour phase epitaxy (MOVPE): while wurtzite GaAs growth is reported for high nominal V/III-ratio in MBE, zinc blende GaAs is formed in MOVPE under apparently the same parameter change (increasing precursor V/III-ratio). Here we show that these observations are not necessarily contradictory, as it may first appear, by providing a consolidated picture covering all regimes in one MOVPE growth machine only. More precisely, we observe wurtzite formation for medium nominal V/III-ratios with a critical sensitivity to the balance between Ga and As supply. Slight deviations from wurtzite conditions will result in zinc blende formation for either low V/III-ratio in the As-limited regime or high V/III-ratio in the Ga-limited regime. Our observations strongly indicate that the applied growth conditions are the crucial ingredients for crystal structure control in GaAs nanowires rather than the growth technique or precursors used. PMID- 26160889 TI - Single-electron and quantum confinement limits in length-scaled silicon nanowires. AB - Quantum-effects will play an important role in both future CMOS and 'beyond CMOS' technologies. By comparing single-electron transistors formed in un-patterned, uniform-width silicon nanowire (SiNW) devices with core widths from ~5-40 nm, and gated lengths of 1 MUm and ~50 nm, we show conditions under which these effects become significant. Coulomb blockade drain-source current-voltage characteristics, and single-electron current oscillations with gate voltage have been observed at room temperature. Detailed electrical characteristics have been measured from 8-300 K. We show that while shortening the nanowire gate length to 50 nm reduces the likelihood of quantum dots to only a few, it increases their influence on the electrical characteristics. This highlights explicitly both the significance of quantum effects for understanding the electrical performance of nominally 'classical' SiNW devices and also their potential for new quantum effect 'beyond CMOS' devices. PMID- 26160886 TI - EXO1 is critical for embryogenesis and the DNA damage response in mice with a hypomorphic Nbs1 allele. AB - The maintenance of genome stability is critical for the suppression of diverse human pathologies that include developmental disorders, premature aging, infertility and predisposition to cancer. The DNA damage response (DDR) orchestrates the appropriate cellular responses following the detection of lesions to prevent genomic instability. The MRE11 complex is a sensor of DNA double strand breaks (DSBs) and plays key roles in multiple aspects of the DDR, including DNA end resection that is critical for signaling and DNA repair. The MRE11 complex has been shown to function both upstream and in concert with the 5' 3' exonuclease EXO1 in DNA resection, but it remains unclear to what extent EXO1 influences DSB responses independently of the MRE11 complex. Here we examine the genetic relationship of the MRE11 complex and EXO1 during mammalian development and in response to DNA damage. Deletion of Exo1 in mice expressing a hypomorphic allele of Nbs1 leads to severe developmental impairment, embryonic death and chromosomal instability. While EXO1 plays a minimal role in normal cells, its loss strongly influences DNA replication, DNA repair, checkpoint signaling and damage sensitivity in NBS1 hypomorphic cells. Collectively, our results establish a key role for EXO1 in modulating the severity of hypomorphic MRE11 complex mutations. PMID- 26160887 TI - Ty1 retrovirus-like element Gag contains overlapping restriction factor and nucleic acid chaperone functions. AB - Ty1 Gag comprises the capsid of virus-like particles and provides nucleic acid chaperone (NAC) functions during retrotransposition in budding yeast. A subgenomic Ty1 mRNA encodes a truncated Gag protein (p22) that is cleaved by Ty1 protease to form p18. p22/p18 strongly inhibits transposition and can be considered an element-encoded restriction factor. Here, we show that only p22 and its short derivatives restrict Ty1 mobility whereas other regions of GAG inhibit mobility weakly if at all. Mutational analyses suggest that p22/p18 is synthesized from either of two closely spaced AUG codons. Interestingly, AUG1p18 and AUG2p18 proteins display different properties, even though both contain a region crucial for RNA binding and NAC activity. AUG1p18 shows highly reduced NAC activity but specific binding to Ty1 RNA, whereas AUG2p18 shows the converse behavior. p22/p18 affects RNA encapsidation and a mutant derivative defective for RNA binding inhibits the RNA chaperone activity of the C-terminal region (CTR) of Gag-p45. Moreover, affinity pulldowns show that p18 and the CTR interact. These results support the idea that one aspect of Ty1 restriction involves inhibition of Gag-p45 NAC functions by p22/p18-Gag interactions. PMID- 26160890 TI - Diagnosing skin disease in primary care: a qualitative study of GPs' approaches. AB - BACKGROUND: Skin diseases are a common reason for consulting a GP. This regular occurrence happens despite most GPs' lack of knowledge and training in skin disease. OBJECTIVES: We aimed to explore different diagnostic approaches of GPs in patients presenting with a dermatological problem. In addition, we aimed to identify strategies used by GPs to handle diagnostic uncertainty in these patients. METHODS: We conducted interviews (20-40 minutes) with 14 GPs using a semi-structured guideline. Recalling encounters with patients with skin disease, GPs described their individual diagnostic strategies. Interviews were taped and transcribed verbatim. Qualitative analysis was conducted by two independent raters using a deductive-inductive approach. RESULTS: We identified several aspects of a complex decision-making process in GPs' diagnostic management of patients with dermatological problems. In the general diagnostic workup, GPs used a broad spectrum of different strategies such as spot diagnosis, stepwise refinement, pattern recognition trigger or test of treatment. GPs reduced diagnostic uncertainty through the identification of red flags, the application of the test of time, therapeutic trials and asking for further advice, including patient referral. CONCLUSIONS: GPs encounter a broad range of dermatological problems in their daily work using a variety of strategies in the workup of these patients. However, in a significant number of patients, there remains diagnostic uncertainty that is mainly reduced by specialist referral. Regular training in the diagnosis and treatment of common dermatological diseases should be offered to all GPs. PMID- 26160891 TI - Perceptions of Indonesian general practitioners in maintaining standards of medical practice at a time of health reform. AB - BACKGROUND: There is little research on how GPs experience the demands of maintaining standards of medical practice in developing countries and what strategies might improve their capability to provide high-quality primary health care (PHC). OBJECTIVE: This study aims to explore the underlying factors, which shape GPs' experience within the Indonesian PHC system and impact on their experience of professional practice. METHODS: A grounded theory approach was applied using semi-structured interviews of 25 purposively selected GPs in West Sumatra, Indonesia. The interviews were analysed inductively through an iterative process of the interplay between empirical data, emerging analysis and theory development. RESULTS: Three major health care systems attribute shaped GPs' experiences of professional practice, including (i) a restricted concept of the PHC system, (ii) lack of regulation of private primary care practice conducted by GPs, midwives, nurses and specialists and (iii) low coverage and inappropriate policy of the health insurance system. CONCLUSION: The findings indicate that a major revision of current health care system is required with a focus on promoting the concept of PHC services to the population, redefining the role of the GP to deliver recognised best practice within available resources, changing the way GPs are remunerated by the public health system and the health insurance industry, policing of the regulations related to the scope of practice of other health care professionals, particularly midwives and nurses, and regulation of prescribing. GPs can be the champions of the PHC service that Indonesia needs, but it requires sustained systematic change. PMID- 26160892 TI - Explaining engagement in self-monitoring among participants of the DESMOND Self monitoring Trial: a qualitative interview study. AB - BACKGROUND: The Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) Self-monitoring Trial reported that people with newly diagnosed type 2 diabetes attending community-based structured education and randomized to self-monitoring of blood glucose (SMBG) or urine monitoring had comparable improvements in biomedical outcomes, but differences in satisfaction with, and continued use of monitoring method, well-being and perceived threat from diabetes. OBJECTIVES: To explore experiences of SMBG and urine monitoring following structured education. We specifically addressed the perceived usefulness of each monitoring method and the associated well-being. METHODS: Qualitative semi-structured interviews with 18 adults with newly diagnosed type 2 diabetes participating in the DESMOND Self-monitoring Trial (SMBG, N=10; urine monitoring, N=8)~12 months into the trial. Analysis was informed by the constant comparative approach. RESULTS: Interviewees reported SMBG as accurate, convenient and useful. Declining use was explained by having established a pattern of managing blood glucose with less frequent monitoring or lack of feedback or encouragement from health care professionals. Many initially positive views of urine monitoring progressively changed due to perceived inaccuracy, leading some to switch to SMBG. Perceiving diabetes as less serious was attributable to lack of symptoms, treatment with diet alone and-in the urine-monitoring group consistently negative readings. Urine monitoring also provided less visible evidence of diabetes and of the effect of behaviour on glucose. CONCLUSIONS: The findings highlight the importance for professionals of considering patients' preferences when using self-monitoring technologies, including how these change over time, when supporting the self-care behaviours of people with type 2 diabetes. PMID- 26160893 TI - The evolution of morphological variants of focal segmental glomerulosclerosis: a repeat biopsy-based observation. AB - BACKGROUND: The Columbia classification employs a systematic, hierarchical approach to define five mutually exclusive variants. Studies have demonstrated differences in baseline clinical characteristics and outcomes among the Columbia classification variants. However, the evolution of the Columbia classification variants of primary focal segmental glomerulosclerosis (FSGS) is unclear. We assessed the evolution of morphological variants in FSGS based on repeat native renal biopsies. METHODS: Twenty-four patients (18 male, 6 female) with idiopathic FSGS who underwent more than one renal biopsy were enrolled in this study; three of these patients underwent three renal biopsies. The patients' clinicopathological features were reviewed. The subtypes of FSGS (2004 Columbia classification) included the collapsing, tip, cellular, perihilar and not otherwise specified (NOS) variants. The evolution of the Columbia classification variants of primary FSGS in each patient was evaluated. RESULTS: The interval between the first and second renal biopsy was 21.95 +/- 24.33 months. No significant differences in laboratory data were noted between the first and second renal biopsy. At the first renal biopsy, 5 patients were classified with collapsing, 5 with tip, 6 with cellular, 2 with perihilar and 6 with NOS variants. At the second renal biopsy, 3 patients were classified with collapsing, 3 with tip lesion, 4 with cellular, 1 with perihilar and 13 with NOS variants. Subtype changes from the first to repeat biopsies occurred in 11 patients, 9 of which progressed from other variants to the NOS variant. CONCLUSION: Repeat renal biopsies are a useful tool for observing FSGS histological changes. The transformation from other subtypes to the NOS variant was the most common change; these alterations were accompanied by clinical progression. PMID- 26160894 TI - New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis. AB - BACKGROUND: The reduced glomerular filtration rate in the advanced stages of chronic kidney disease (CKD) leads to plasma accumulation of uraemic retention solutes including proteins. It has been hypothesized that these changes may, at least in part, be responsible for CKD-associated morbidity and mortality. However, most studies focused on the role of individual proteins, while a holistic, large-scale, integrative approach may generate significant additional insight. METHODS: In a discovery study, we analysed the plasma proteome of patients with stage 2-3 CKD (n = 14) and stage 5 CKD with haemodialysis (HD) (n = 15), using high-resolution LC-MS/MS analysis. Selected results were validated in a cohort of 40 patients with different CKD stages with or without HD, using ELISA. RESULTS: Of a total of 2054 detected proteins, 127 displayed lower, while 206 displayed higher abundance in the plasma of patients on HD. Molecular pathway analysis confirmed the modification of known processes involved in CKD complications, including decreased haemostasis and increased inflammation, complement activation and vascular damage. In addition, we identified the plasma increase during CKD progression of lysozyme C and leucine-rich alpha-2 glycoprotein, two proteins related to vascular damage and heart failure. High level of leucine-rich alpha-2 glycoprotein was associated with higher mortality in stage 5 CKD patients on HD. CONCLUSIONS: This study provides for the first time a comprehensive assessment of CKD plasma proteome, contributing to new knowledge and potential markers of CKD. These results will serve as a basis for future studies investigating the relevance of these molecules in CKD associated morbidity and mortality. PMID- 26160895 TI - Outcomes of transient ischemic attack in maintenance dialysis patients and those with chronic kidney disease. AB - BACKGROUND: In-hospital outcomes of transient ischemic attack (TIA) in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) requiring maintenance dialysis are largely unknown. We evaluated TIA-related in-hospital outcomes in these patients using a national database. METHODS: Our study is observational in nature. Data from all adult (>= 18 years) patients admitted to US hospitals between 2005 and 2011 with a primary discharge diagnosis of TIA and secondary diagnosis of CKD and ESRD were included using the Nationwide In-Patient Sample. We aimed to compare the following TIA-related outcomes between CKD and ESRD patients: (i) degree of disability (mainly functional status) derived from discharge destination, (ii) length of stay, (iii) charges of hospitalization, and (iv) mortality. The comparisons of TIA-related mortality and discharge outcomes between CKD and ESRD were analyzed after adjusting for potential confounders using logistic regression analysis. We adjusted for age, sex, co-morbidities, hospital size and hospital teaching status. RESULTS: A total of 18 316 dialysis and 67 256 CKD patients were admitted with TIA in the study period (2005-11). On univariate analysis, there was no difference in the rates of moderate-to-severe disability (20.5% versus 20.2%, P = 0.7) and in-hospital mortality (0.4% versus 0.2%, P = 0.07) in ESRD patients compared with those with CKD. After adjusting for age, sex and potential confounders, ESRD patients with TIA had higher odds of moderate-to-severe disability at discharge [odds ratio (OR): 1.53, 95% confidence interval (CI): 1.37-1.71, P <= 0.0001] and in-hospital death (OR: 2.87, 95% CI: 1.29-6.37, P = 0.009). CONCLUSION: ESRD patients with TIA have significantly higher rates of moderate-to-severe disability at discharge and in-hospital mortality when compared with the patients of other stages of CKD who are not dialysis-dependent. PMID- 26160896 TI - Electrocardiographic Measures and Prediction of Cardiovascular and Noncardiovascular Death in CKD. AB - Limited studies have assessed the resting 12-lead electrocardiogram (ECG) as a screening test in intermediate risk populations. We evaluated whether a panel of common ECG parameters are independent predictors of mortality risk in a prospective cohort of participants with CKD. The Chronic Renal Insufficiency Cohort (CRIC) study enrolled 3939 participants with eGFR<70 ml/min per 1.73 m(2) from June 2003 to September 2008. Over a median follow-up of 7.5 years, 750 participants died. After adjudicating the initial 497 deaths, we identified 256 cardiovascular and 241 noncardiovascular deaths. ECG metrics were independent risk markers for cardiovascular death (hazard ratio, 95% confidence interval): PR interval >=200 ms (1.62, 1.19-2.19); QRS interval 100-119 ms (1.64, 1.20-2.25) and >=120 ms (1.75, 1.17-2.62); corrected QT (QTc) interval >=450 ms in men or >=460 ms in women (1.72, 1.19-2.49); and heart rate 60-90 beats per minute (1.21, 0.89-1.63) and >=90 beats per minute (2.35, 1.03-5.33). Most ECG measures were stronger markers of risk for cardiovascular death than for all-cause mortality or noncardiovascular death. Adding these intervals to a comprehensive model of cardiorenal risk factors increased the C-statistic for cardiovascular death from 0.77 to 0.81 (P<0.001). Furthermore, adding ECG metrics to the model adjusted for standard risk factors resulted in a net reclassification of 12.1% (95% confidence interval 8.1%-16.0%). These data suggest common ECG metrics are independent risk factors for cardiovascular death and enhance the ability to predict death events in a population with CKD. PMID- 26160897 TI - Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1 Dependent Adhesion Mechanism. AB - Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C(high) monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis. PMID- 26160898 TI - Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization. AB - Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X4) blocker 5-BDBD. Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X4 channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X4 channels as mechanotransducers in podocytes. PMID- 26160899 TI - Endothelin signaling activates Mef2c expression in the neural crest through a MEF2C-dependent positive-feedback transcriptional pathway. AB - Endothelin signaling is essential for neural crest development, and dysregulated Endothelin signaling is associated with several neural crest-related disorders, including Waardenburg and other syndromes. However, despite the crucial roles of this pathway in neural crest development and disease, the transcriptional effectors directly activated by Endothelin signaling during neural crest development remain incompletely elucidated. Here, we establish that the MADS box transcription factor MEF2C is an immediate downstream transcriptional target and effector of Endothelin signaling in the neural crest. We show that Endothelin signaling activates Mef2c expression in the neural crest through a conserved enhancer in the Mef2c locus and that CRISPR-mediated deletion of this Mef2c neural crest enhancer from the mouse genome abolishes Endothelin induction of Mef2c expression. Moreover, we demonstrate that Endothelin signaling activates neural crest expression of Mef2c by de-repressing MEF2C activity through a Calmodulin-CamKII-histone deacetylase signaling cascade. Thus, these findings identify a MEF2C-dependent, positive-feedback mechanism for Endothelin induction and establish MEF2C as an immediate transcriptional effector and target of Endothelin signaling in the neural crest. PMID- 26160900 TI - Anteroposterior patterning of Drosophila ocelli requires an anti-repressor mechanism within the hh pathway mediated by the Six3 gene Optix. AB - In addition to compound eyes, most insects possess a set of three dorsal ocelli that develop at the vertices of a triangular cuticle patch, forming the ocellar complex. The wingless and hedgehog signaling pathways, together with the transcription factor encoded by orthodenticle, are known to play major roles in the specification and patterning of the ocellar complex. Specifically, hedgehog is responsible for the choice between ocellus and cuticle fates within the ocellar complex primordium. However, the interactions between signals and transcription factors known to date do not fully explain how this choice is controlled. We show that this binary choice depends on dynamic changes in the domains of hedgehog signaling. In this dynamics, the restricted expression of engrailed, a hedgehog signaling target, is key because it defines a domain within the complex where hedgehog transcription is maintained while the pathway activity is blocked. We further show that the Drosophila Six3, optix, is expressed in and required for the development of the anterior ocellus specifically, limiting the ocellar expression domain of en. This finding confirms previous genetic evidence that the spatial allocation of the primordia of anterior and posterior ocelli is differentially regulated, which may apply to the patterning of the insect head in general. PMID- 26160901 TI - Efficient CRISPR-mediated gene targeting and transgene replacement in the beetle Tribolium castaneum. AB - Gene-editing techniques are revolutionizing the way we conduct genetics in many organisms. The CRISPR/Cas nuclease has emerged as a highly versatile, efficient and affordable tool for targeting chosen sites in the genome. Beyond its applications in established model organisms, CRISPR technology provides a platform for genetic intervention in a wide range of species, limited only by our ability to deliver it to cells and to select mutations efficiently. Here, we test the CRISPR technology in an emerging insect model and pest, the beetle Tribolium castaneum. We use simple assays to test CRISPR/Cas activity, we demonstrate efficient expression of guide RNAs and Cas9 from Tribolium U6 and hsp68 promoters and we test the efficiency of knockout and knock-in approaches in Tribolium. We find that 55-80% of injected individuals carry mutations (indels) generated by non-homologous end joining, including mosaic bi-allelic knockouts; 71-100% carry such mutations in their germ line and transmit them to the next generation. We show that CRISPR-mediated gene knockout of the Tribolium E-cadherin gene causes defects in dorsal closure, which is consistent with RNAi-induced phenotypes. Homology-directed knock-in of marker transgenes was observed in 14% of injected individuals and transmitted to the next generation by 6% of injected individuals. Previous work in Tribolium mapped a large number of transgene insertions associated with developmental phenotypes and enhancer traps. We present an efficient method for re-purposing these insertions, via CRISPR-mediated replacement of these transgenes by new constructs. PMID- 26160903 TI - Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea. AB - Transcriptional regulatory networks are essential during the formation and differentiation of organs. The transcription factor N-myc is required for proper morphogenesis of the cochlea and to control correct patterning of the organ of Corti. We show here that the Otx2 gene, a mammalian ortholog of the Drosophila orthodenticle homeobox gene, is a crucial target of N-myc during inner ear development. Otx2 expression is lost in N-myc mouse mutants, and N-myc misexpression in the chick inner ear leads to ectopic expression of Otx2. Furthermore, Otx2 enhancer activity is increased by N-myc misexpression, indicating that N-myc may directly regulate Otx2. Inactivation of Otx2 in the mouse inner ear leads to ectopic expression of prosensory markers in non-sensory regions of the cochlear duct. Upon further differentiation, these domains give rise to an ectopic organ of Corti, together with the re-specification of non sensory areas into sensory epithelia, and the loss of Reissner's membrane. Therefore, the Otx2-positive domain of the cochlear duct shows a striking competence to develop into a mirror-image copy of the organ of Corti. Taken together, these data show that Otx2 acts downstream of N-myc and is essential for patterning and spatial restriction of the sensory domain of the mammalian cochlea. PMID- 26160902 TI - Dachsous1b cadherin regulates actin and microtubule cytoskeleton during early zebrafish embryogenesis. AB - Dachsous (Dchs), an atypical cadherin, is an evolutionarily conserved regulator of planar cell polarity, tissue size and cell adhesion. In humans, DCHS1 mutations cause pleiotropic Van Maldergem syndrome. Here, we report that mutations in zebrafish dchs1b and dchs2 disrupt several aspects of embryogenesis, including gastrulation. Unexpectedly, maternal zygotic (MZ) dchs1b mutants show defects in the earliest developmental stage, egg activation, including abnormal cortical granule exocytosis (CGE), cytoplasmic segregation, cleavages and maternal mRNA translocation, in transcriptionally quiescent embryos. Later, MZdchs1b mutants exhibit altered dorsal organizer and mesendodermal gene expression, due to impaired dorsal determinant transport and Nodal signaling. Mechanistically, MZdchs1b phenotypes can be explained in part by defective actin or microtubule networks, which appear bundled in mutants. Accordingly, disruption of actin cytoskeleton in wild-type embryos phenocopied MZdchs1b mutant defects in cytoplasmic segregation and CGE, whereas interfering with microtubules in wild type embryos impaired dorsal organizer and mesodermal gene expression without perceptible earlier phenotypes. Moreover, the bundled microtubule phenotype was partially rescued by expressing either full-length Dchs1b or its intracellular domain, suggesting that Dchs1b affects microtubules and some developmental processes independent of its known ligand Fat. Our results indicate novel roles for vertebrate Dchs in actin and microtubule cytoskeleton regulation in the unanticipated context of the single-celled embryo. PMID- 26160904 TI - Regulator of G-protein signaling 2 (RGS2) suppresses premature calcium release in mouse eggs. AB - During oocyte maturation, capacity and sensitivity of Ca(2+) signaling machinery increases dramatically, preparing the metaphase II (MII)-arrested egg for fertilization. Upon sperm-egg fusion, Ca(2+) release from IP3-sensitive endoplasmic reticulum stores results in cytoplasmic Ca(2+) oscillations that drive egg activation and initiate early embryo development. Premature Ca(2+) release can cause parthenogenetic activation prior to fertilization; thus, preventing inappropriate Ca(2+) signaling is crucial for ensuring robust MII arrest. Here, we show that regulator of G-protein signaling 2 (RGS2) suppresses Ca(2+) release in MII eggs. Rgs2 mRNA was recruited for translation during oocyte maturation, resulting in ~ 20-fold more RGS2 protein in MII eggs than in fully grown immature oocytes. Rgs2-siRNA-injected oocytes matured to MII; however, they had increased sensitivity to low pH and acetylcholine (ACh), which caused inappropriate Ca(2+) release and premature egg activation. When matured in vitro, RGS2-depleted eggs underwent spontaneous Ca(2+) increases that were sufficient to cause premature zona pellucida conversion. Rgs2(-/-) females had reduced litter sizes, and their eggs had increased sensitivity to low pH and ACh. Rgs2(-/-) eggs also underwent premature zona pellucida conversion in vivo. These findings indicate that RGS2 functions as a brake to suppress premature Ca(2+) release in eggs that are poised on the brink of development. PMID- 26160906 TI - Effect of relative nanohole position on colour purity of ultrathin plasmonic subtractive colour filters. AB - Plasmonic subtractive color filters through patterning periodic nanostructures on ultrathin Ag films deposited on a glass substrate, exhibiting good durability, simple fabrication, and flexible color tunability, have attracted considerable attention due to their tremendous potential applications. While previous studies have mainly focused on their extraordinary physical mechanisms, color purity, which is another key parameter for high quality imaging applications, has been much less investigated. In this work, we demonstrate that the relative position of nanoholes patterned on ultrathin Ag films can largely affect the color purity of plasmonic subtractive color filters. The calculated results agree reasonably well with the experimental data, revealing that the purity of subtractive colors can be improved by changing the nanohole arrays from square lattice to triangular lattice without reducing transmission at visible frequencies. In addition, underlying mechanisms are clarified by systematically analyzing the dominant valley in transmission spectra. PMID- 26160905 TI - Scalloped and Yorkie are required for cell cycle re-entry of quiescent cells after tissue damage. AB - Regeneration of damaged tissues typically requires a population of active stem cells. How damaged tissue is regenerated in quiescent tissues lacking a stem cell population is less well understood. We used a genetic screen in the developing Drosophila melanogaster eye to investigate the mechanisms that trigger quiescent cells to re-enter the cell cycle and proliferate in response to tissue damage. We discovered that Hippo signaling regulates compensatory proliferation after extensive cell death in the developing eye. Scalloped and Yorkie, transcriptional effectors of the Hippo pathway, drive Cyclin E expression to induce cell cycle re entry in cells that normally remain quiescent in the absence of damage. Ajuba, an upstream regulator of Hippo signaling that functions as a sensor of epithelial integrity, is also required for cell cycle re-entry. Thus, in addition to its well-established role in modulating proliferation during periods of tissue growth, Hippo signaling maintains homeostasis by regulating quiescent cell populations affected by tissue damage. PMID- 26160907 TI - Response to: Randomized controlled trial of vertebroplasty versus kyphoplasty in the treatment of vertebral compression fractures. PMID- 26160908 TI - Response to: 'Is rituximab effective for IgG4-related disease in the long term? Experience of cases treated with rituximab for 4 years' by Yamamoto et al. PMID- 26160909 TI - Response to: 'Paracetamol: is all the concern valid?' by Schwarz and Mullins. PMID- 26160910 TI - Antigen-specific T cell therapies for cancer. AB - Adoptively transferred antigen-specific T cells that recognize tumor antigens through their native receptors have many potential benefits as treatment for virus-associated diseases and malignancies, due to their ability to selectively recognize tumor antigens, expand and persist to provide long-term protection. Infusions of T cells targeting Epstein-Barr virus (EBV) antigens have shown encouraging response rates in patients with post-transplant lymphoproliferative disease as well as EBV-positive lymphomas and nasopharyngeal cancer, although a recent study also showed that human papilloma virus-reactive T cells can induce complete regression of metastatic cervical cancer. This strategy is also being evaluated to target non-viral tumor-associated antigens. Targeting these less immunogenic antigens is more challenging, as tumor antigens are generally weak, and high avidity T cells specific for self-antigens are deleted in the thymus, but tumor responses have been reported. Current research focusses on defining factors that promote in vivo persistence of transferred cells and ameliorate the immunosuppressive microenvironment. To this end, investigators are evaluating the effects of combining adoptive transfer of antigen-specific T cells with other immunotherapy moieties such as checkpoint inhibitors. Genetic modification of infused T cells may also be used to overcome tumor evasion mechanisms, and vaccines may be used to promote in vivo proliferation. PMID- 26160911 TI - Cln1 gene disruption in mice reveals a common pathogenic link between two of the most lethal childhood neurodegenerative lysosomal storage disorders. AB - Neurodegeneration is a devastating manifestation in the majority of >50 lysosomal storage disorders (LSDs). Neuronal ceroid lipofuscinoses (NCLs) are the most common childhood neurodegenerative LSDs. Mutations in 13 different genes (called CLNs) underlie various types of NCLs, of which the infantile NCL (INCL) and congenital NCL (CNCL) are the most lethal. Although inactivating mutations in the CLN1 gene encoding palmitoyl-protein thioesterase-1 (PPT1) cause INCL, those in the CLN10 gene encoding cathepsin D (CD) underlie CNCL. PPT1 is a lysosomal thioesterase that cleaves the thioester linkage in S-acylated proteins required for their degradation by lysosomal hydrolases like CD. Thus, PPT1 deficiency causes lysosomal accumulation of these lipidated proteins (major constituents of ceroid) leading to INCL. We sought to determine whether there is a common pathogenic link between INCL and CNCL. Using biochemical, histological and confocal microscopic analyses of brain tissues and cells from Cln1(-/-) mice that mimic INCL, we uncovered that Cln10/CD is overexpressed. Although synthesized in the endoplasmic reticulum, the CD-precursor protein (pro-CD) is transported through endosome to the lysosome where it is proteolytically processed to enzymatically active-CD. We found that despite Cln10 overexpression, the maturation of pro-CD to enzymatically active-CD in lysosome was disrupted. This defect impaired lysosomal degradative function causing accumulation of undegraded cargo in lysosome leading to INCL. Notably, treatment of intact Cln1(-/-) mice as well as cultured brain cells derived from these animals with a thioesterase mimetic small molecule, N-tert-butyl-hydroxylamine, ameliorated the CD-processing defect. Our findings are significant in that they define a pathway in which Cln1 mutations disrupt the maturation of a major degradative enzyme in lysosome contributing to neuropathology in INCL and suggest that lysosomal CD deficiency is a common pathogenic link between INCL and CNCL. PMID- 26160912 TI - Recent advances in understanding the genetic architecture of type 2 diabetes. AB - Genome-wide association (GWAS) and sequencing studies are providing new insights into the genetic basis of type 2 diabetes (T2D) and the inter-individual variation in glycemic traits, including levels of glucose, insulin, proinsulin and hemoglobin A1c (HbA1c). At the end of 2011, established loci (P < 5 * 10(-8)) totaled 55 for T2D and 32 for glycemic traits. Since then, most new loci have been detected by analyzing common [minor allele frequency (MAF)>0.05] variants in increasingly large sample sizes from populations around the world, and in trans ancestry studies that successfully combine data from diverse populations. Most recently, advances in sequencing have led to the discovery of four loci for T2D or glycemic traits based on low-frequency (0.005 < MAF <= 0.05) variants, and additional low-frequency, potentially functional variants have been identified at GWAS loci. Established published loci now total ~88 for T2D and 83 for one or more glycemic traits, and many additional loci likely remain to be discovered. Future studies will build on these successes by identifying additional loci and by determining the pathogenic effects of the underlying variants and genes. PMID- 26160913 TI - Genetics of human metabolism: an update. AB - Genome-wide association studies with metabolomics (mGWAS) identify genetically influenced metabotypes (GIMs), their ensemble defining the heritable part of every human's metabolic individuality. Knowledge of genetic variation in metabolism has many applications of biomedical and pharmaceutical interests, including the functional understanding of genetic associations with clinical end points, design of strategies to correct dysregulations in metabolic disorders and the identification of genetic effect modifiers of metabolic disease biomarkers. Furthermore, it has been shown that GIMs provide testable hypotheses for functional genomics and metabolomics and for the identification of novel gene functions and metabolite identities. mGWAS with growing sample sizes and increasingly complex metabolic trait panels are being conducted, allowing for more comprehensive and systems-based downstream analyses. The generated large datasets of genetic associations can now be mined by the biomedical research community and provide valuable resources for hypothesis-driven studies. In this review, we provide a brief summary of the key aspects of mGWAS, followed by an update of recently published mGWAS. We then discuss new approaches of integrating and exploring mGWAS results and finish by presenting selected applications of GIMs in recent studies. PMID- 26160914 TI - Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer's disease. AB - Phospholipid transfer protein (PLTP) is a widely expressed lipid transfer protein participating in the transport of cholesterol and other lipids in the plasma and peripheral tissues. Recently, elevated amyloid beta (Abeta) in young and aged PLTP-deficient brains had been reported. However, the role of PLTP in amyloid precursor protein (APP) processing and Alzheimer's disease (AD) pathology remains elusive. Here we first found that deficiency of PLTP accelerated memory dysfunction in APP/PS1DeltaE9 AD model mice at the age of 3 months. Further characterization showed that PLTP deficiency increased soluble Abeta peptides, and intracellular accumulation of Abeta was illustrated, which might be due to disrupted APP turnover and the enhanced amyloidogenic pathway. Besides, reduced brain-derived neurotrophic factor (BDNF) was found in PLTP-deficient APP/PS1DeltaE9 mice, and the BDNF level was negatively correlated with Abeta42 content, instead of Abeta40 content. In addition, autophagic dysfunction was found in the PLTP-deficient APP/PS1DeltaE9 mice. Our data presented a novel model to link phospholipid metabolism to APP processing and also suggested that PLTP played an important role in Abeta metabolism and would be useful to further elucidate functions of PLTP in AD susceptibility. PMID- 26160915 TI - COA6 is a mitochondrial complex IV assembly factor critical for biogenesis of mtDNA-encoded COX2. AB - Biogenesis of complex IV of the mitochondrial respiratory chain requires assembly factors for subunit maturation, co-factor attachment and stabilization of intermediate assemblies. A pathogenic mutation in COA6, leading to substitution of a conserved tryptophan for a cysteine residue, results in a loss of complex IV activity and cardiomyopathy. Here, we demonstrate that the complex IV defect correlates with a severe loss in complex IV assembly in patient heart but not fibroblasts. Complete loss of COA6 activity using gene editing in HEK293T cells resulted in a profound growth defect due to complex IV deficiency, caused by impaired biogenesis of the copper-bound mitochondrial DNA-encoded subunit COX2 and subsequent accumulation of complex IV assembly intermediates. We show that the pathogenic mutation in COA6 does not affect its import into mitochondria but impairs its maturation and stability. Furthermore, we show that COA6 has the capacity to bind copper and can associate with newly translated COX2 and the mitochondrial copper chaperone SCO1. Our data reveal that COA6 is intricately involved in the copper-dependent biogenesis of COX2. PMID- 26160916 TI - Reply: Diagnostic and management modalities in early tubal pregnancy with focus on safety. PMID- 26160917 TI - Diagnostic and management modalities in early tubal ectopic pregnancy with focus on safety. PMID- 26160918 TI - Engaging new scientific horizons. PMID- 26160920 TI - EUROPE. Scientists dread Greek exit from the euro. PMID- 26160921 TI - CLIMATE CHANGE. Bumblebees aren't keeping up with a warming planet. PMID- 26160922 TI - WOMEN IN SCIENCE. Plan to drop goals for women roils Japanese science. PMID- 26160923 TI - BIOMEDICINE. Targeting copper to treat breast cancer. PMID- 26160925 TI - PLANETARY SCIENCE. Pluto caps one man's odyssey. PMID- 26160924 TI - Cancer's copper connections. PMID- 26160926 TI - SCIENCE POLICY. U.S. to review agricultural biotech regulations. PMID- 26160927 TI - Deep sleep. PMID- 26160928 TI - Rolling out a welcome mat for waste. PMID- 26160929 TI - OPTICS. 150 years of Maxwell's equations. PMID- 26160930 TI - HYDROLOGY. Water, bound and mobile. PMID- 26160932 TI - ECONOMICS. Intellectuals and the rise of the modern economy. PMID- 26160931 TI - HIV. The modern era of HIV-1 vaccine development. PMID- 26160933 TI - STRUCTURAL BIOLOGY. COPI gets a fancy new coat. PMID- 26160934 TI - OCEANS. Managing mining of the deep seabed. PMID- 26160935 TI - Meeting of the minds: Send your stories. PMID- 26160937 TI - Reviewing Einstein. PMID- 26160938 TI - ORGANIC SYNTHESIS. Comment on "Asymmetric syntheses of sceptrin and massadine and evidence for biosynthetic enantiodivergence". AB - Ma et al. (Reports, 10 October 2014, p. 219) report asymmetric syntheses of sceptrin and massadine and, through a stereochemical reassignment, claim to "uncover enantiodivergence as a new biosynthetic paradigm for natural products." We challenge and clarify this claim with relevant examples from the literature of this well-known phenomenon of enantiodivergent congener biosynthesis within the same producing organism. PMID- 26160939 TI - ORGANIC SYNTHESIS. Response to Comment on "Asymmetric syntheses of sceptrin and massadine and evidence for biosynthetic enantiodivergence". AB - Sherman et al. commented on the precedence of enantiodivergence, listing a number of congeneric natural products with opposite chirality. However, these "congeners" are not derived from enantiodivergent biosyntheses. Instead, they are antipodes arising from separate enantiomeric biosyntheses. A distinct feature of the biosynthesis of the cyclic pyrrole-imidazole dimers is the production of antipodal congeners without the corresponding enantiomers. PMID- 26160940 TI - SOFT ROBOTICS. A 3D-printed, functionally graded soft robot powered by combustion. AB - Roboticists have begun to design biologically inspired robots with soft or partially soft bodies, which have the potential to be more robust and adaptable, and safer for human interaction, than traditional rigid robots. However, key challenges in the design and manufacture of soft robots include the complex fabrication processes and the interfacing of soft and rigid components. We used multimaterial three-dimensional (3D) printing to manufacture a combustion-powered robot whose body transitions from a rigid core to a soft exterior. This stiffness gradient, spanning three orders of magnitude in modulus, enables reliable interfacing between rigid driving components (controller, battery, etc.) and the primarily soft body, and also enhances performance. Powered by the combustion of butane and oxygen, this robot is able to perform untethered jumping. PMID- 26160941 TI - APPLIED PHYSICS. Mid-infrared plasmonic biosensing with graphene. AB - Infrared spectroscopy is the technique of choice for chemical identification of biomolecules through their vibrational fingerprints. However, infrared light interacts poorly with nanometric-size molecules. We exploit the unique electro optical properties of graphene to demonstrate a high-sensitivity tunable plasmonic biosensor for chemically specific label-free detection of protein monolayers. The plasmon resonance of nanostructured graphene is dynamically tuned to selectively probe the protein at different frequencies and extract its complex refractive index. Additionally, the extreme spatial light confinement in graphene up to two orders of magnitude higher than in metals-produces an unprecedentedly high overlap with nanometric biomolecules, enabling superior sensitivity in the detection of their refractive index and vibrational fingerprints. The combination of tunable spectral selectivity and enhanced sensitivity of graphene opens exciting prospects for biosensing. PMID- 26160942 TI - GALAXY EVOLUTION. An over-massive black hole in a typical star-forming galaxy, 2 billion years after the Big Bang. AB - Supermassive black holes (SMBHs) and their host galaxies are generally thought to coevolve, so that the SMBH achieves up to about 0.2 to 0.5% of the host galaxy mass in the present day. The radiation emitted from the growing SMBH is expected to affect star formation throughout the host galaxy. The relevance of this scenario at early cosmic epochs is not yet established. We present spectroscopic observations of a galaxy at redshift z = 3.328, which hosts an actively accreting, extremely massive BH, in its final stages of growth. The SMBH mass is roughly one-tenth the mass of the entire host galaxy, suggesting that it has grown much more efficiently than the host, contrary to models of synchronized coevolution. The host galaxy is forming stars at an intense rate, despite the presence of a SMBH-driven gas outflow. PMID- 26160943 TI - ANIMAL PHYSIOLOGY. Exceptionally low daily energy expenditure in the bamboo eating giant panda. AB - The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet. PMID- 26160944 TI - WATER RESOURCES. Hydrologic connectivity constrains partitioning of global terrestrial water fluxes. AB - Continental precipitation not routed to the oceans as runoff returns to the atmosphere as evapotranspiration. Partitioning this evapotranspiration flux into interception, transpiration, soil evaporation, and surface water evaporation is difficult using traditional hydrological methods, yet critical for understanding the water cycle and linked ecological processes. We combined two large-scale flux partitioning approaches to quantify evapotranspiration subcomponents and the hydrologic connectivity of bound, plant-available soil waters with more mobile surface waters. Globally, transpiration is 64 +/- 13% (mean +/- 1 standard deviation) of evapotranspiration, and 65 +/- 26% of evaporation originates from soils and not surface waters. We estimate that 38 +/- 28% of surface water is derived from the plant-accessed soil water pool. This limited connectivity between soil and surface waters fundamentally structures the physical and biogeochemical interactions of water transiting through catchments. PMID- 26160945 TI - CLIMATE CHANGE. Climate change impacts on bumblebees converge across continents. AB - For many species, geographical ranges are expanding toward the poles in response to climate change, while remaining stable along range edges nearest the equator. Using long-term observations across Europe and North America over 110 years, we tested for climate change-related range shifts in bumblebee species across the full extents of their latitudinal and thermal limits and movements along elevation gradients. We found cross-continentally consistent trends in failures to track warming through time at species' northern range limits, range losses from southern range limits, and shifts to higher elevations among southern species. These effects are independent of changing land uses or pesticide applications and underscore the need to test for climate impacts at both leading and trailing latitudinal and thermal limits for species. PMID- 26160946 TI - PLACE CELLS. Autoassociative dynamics in the generation of sequences of hippocampal place cells. AB - Neuronal circuits produce self-sustaining sequences of activity patterns, but the precise mechanisms remain unknown. Here we provide evidence for autoassociative dynamics in sequence generation. During sharp-wave ripple (SWR) events, hippocampal neurons express sequenced reactivations, which we show are composed of discrete attractors. Each attractor corresponds to a single location, the representation of which sharpens over the course of several milliseconds, as the reactivation focuses at that location. Subsequently, the reactivation transitions rapidly to a spatially discontiguous location. This alternation between sharpening and transition occurs repeatedly within individual SWRs and is locked to the slow-gamma (25 to 50 hertz) rhythm. These findings support theoretical notions of neural network function and reveal a fundamental discretization in the retrieval of memory in the hippocampus, together with a function for gamma oscillations in the control of attractor dynamics. PMID- 26160947 TI - NEURONAL MODELING. Single-trial spike trains in parietal cortex reveal discrete steps during decision-making. AB - Neurons in the macaque lateral intraparietal (LIP) area exhibit firing rates that appear to ramp upward or downward during decision-making. These ramps are commonly assumed to reflect the gradual accumulation of evidence toward a decision threshold. However, the ramping in trial-averaged responses could instead arise from instantaneous jumps at different times on different trials. We examined single-trial responses in LIP using statistical methods for fitting and comparing latent dynamical spike-train models. We compared models with latent spike rates governed by either continuous diffusion-to-bound dynamics or discrete "stepping" dynamics. Roughly three-quarters of the choice-selective neurons we recorded were better described by the stepping model. Moreover, the inferred steps carried more information about the animal's choice than spike counts. PMID- 26160948 TI - PROTEIN STRUCTURE. Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels. AB - Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane embedded sterol sensors that regulate the cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited. Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with TM3 and TM4 contributing to homotrimerization. The six TMs enclose a V-shaped cavity that can accommodate a diacylglycerol molecule. A homology-based structural model of human Insig-2, together with biochemical characterizations, suggest that the central cavity of Insig-2 accommodates 25-hydroxycholesterol, whereas TM3 and TM4 engage in Scap binding. These analyses provide an important framework for further functional and mechanistic understanding of Insig proteins and the sterol regulatory element-binding protein pathway. PMID- 26160949 TI - VESICULAR TRANSPORT. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly. AB - Transport of material within cells is mediated by trafficking vesicles that bud from one cellular compartment and fuse with another. Formation of a trafficking vesicle is driven by membrane coats that localize cargo and polymerize into cages to bend the membrane. Although extensive structural information is available for components of these coats, the heterogeneity of trafficking vesicles has prevented an understanding of how complete membrane coats assemble on the membrane. We combined cryo-electron tomography, subtomogram averaging, and cross linking mass spectrometry to derive a complete model of the assembled coat protein complex I (COPI) coat involved in traffic between the Golgi and the endoplasmic reticulum. The highly interconnected COPI coat structure contradicted the current "adaptor-and-cage" understanding of coated vesicle formation. PMID- 26160950 TI - Getting noticed is half the battle. PMID- 26160951 TI - SEA-LEVEL RISE. Sea-level rise due to polar ice-sheet mass loss during past warm periods. AB - Interdisciplinary studies of geologic archives have ushered in a new era of deciphering magnitudes, rates, and sources of sea-level rise from polar ice-sheet loss during past warm periods. Accounting for glacial isostatic processes helps to reconcile spatial variability in peak sea level during marine isotope stages 5e and 11, when the global mean reached 6 to 9 meters and 6 to 13 meters higher than present, respectively. Dynamic topography introduces large uncertainties on longer time scales, precluding robust sea-level estimates for intervals such as the Pliocene. Present climate is warming to a level associated with significant polar ice-sheet loss in the past. Here, we outline advances and challenges involved in constraining ice-sheet sensitivity to climate change with use of paleo-sea level records. PMID- 26160953 TI - Erratum for the Report "On the origin of near-infrared extragalactic background light anisotropy" by M. Zemcov, J. Smidt, T. Arai, J. Bock, A. Cooray, Y. Gong, M. G. Kim, P. Korngut, A. Lam, D. H. Lee, T. Matsumoto, S. Matsuura, U. W. Nam, G. Roudier, K. Tsumura, T. Wada. PMID- 26160954 TI - Erratum for the Report "The fastest unbound star in our Galaxy ejected by a thermonuclear supernova" by S. Geier, F. Furst, E. Ziegerer, T. Kupfer, U. Heber, A. Irrgang, B. Wang, Z. Liu, Z. Han, B. Sesar, D. Levitan, R. Kotak, E. Magnier, K. Smith, W. S. Burgett, K. Chambers, H. Flewelling, N. Kaiser, R. Wainscoat, C. Waters. PMID- 26160952 TI - IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system. AB - Immune cells function in an interacting hierarchy that coordinates the activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology. PMID- 26160956 TI - Orai3 Surface Accumulation and Calcium Entry Evoked by Vascular Endothelial Growth Factor. AB - OBJECTIVE: Vascular endothelial growth factor (VEGF) acts, in part, by triggering calcium ion (Ca(2+)) entry. Here, we sought understanding of a Synta66-resistant Ca(2+) entry pathway activated by VEGF. APPROACH AND RESULTS: Measurement of intracellular Ca(2+) in human umbilical vein endothelial cells detected a Synta66 resistant component of VEGF-activated Ca(2+) entry that occurred within 2 minutes after VEGF exposure. Knockdown of the channel-forming protein Orai3 suppressed this Ca(2+) entry. Similar effects occurred in 3 further types of human endothelial cell. Orai3 knockdown was inhibitory for VEGF-dependent endothelial tube formation in Matrigel in vitro and in vivo in the mouse. Unexpectedly, immunofluorescence and biotinylation experiments showed that Orai3 was not at the surface membrane unless VEGF was applied, after which it accumulated in the membrane within 2 minutes. The signaling pathway coupling VEGF to the effect on Orai3 involved activation of phospholipase Cgamma1, Ca(2+) release, cytosolic group IV phospholipase A2alpha, arachidonic acid production, and, in part, microsomal glutathione S-transferase 2, an enzyme which catalyses the formation of leukotriene C4 from arachidonic acid. Shear stress reduced microsomal glutathione S-transferase 2 expression while inducing expression of leukotriene C4 synthase, suggesting reciprocal regulation of leukotriene C4-synthesizing enzymes and greater role of microsomal glutathione S-transferase 2 in low shear stress. CONCLUSIONS: VEGF signaling via arachidonic acid and arachidonic acid metabolism causes Orai3 to accumulate at the cell surface to mediate Ca(2+) entry and downstream endothelial cell remodeling. PMID- 26160957 TI - Fibroblast Angiotensin II Type 1a Receptors Contribute to Angiotensin II-Induced Medial Hyperplasia in the Ascending Aorta. AB - OBJECTIVE: Angiotensin II (Ang II) infusion causes aortic medial thickening via stimulation of angiotensin II type 1a (AT1a) receptors. The purpose of this study was to determine the cellular loci of AT1a receptors that mediate this Ang II induced aortic pathology. APPROACH AND RESULTS: Saline or Ang II was infused into AT1a receptor floxed mice expressing Cre under control of cell-specific promoters. Initially, AT1a receptors were depleted in aortic smooth muscle cell and endothelium by expressing Cre under control of SM22 and Tie2 promoters, respectively. Deletion of AT1a receptors in either cell type had no effect on Ang II-induced medial thickening. To determine whether this effect was related to neural stimulation, AT1a receptors were depleted using an enolase 2-driven Cre. Depletion of AT1a receptors in neural cells attenuated Ang II-induced medial thickening of the ascending, but not descending aorta. Lineage tracking studies, using ROSA26-LacZ, demonstrated that enolase 2 was also expressed in adventitial cells adjacent to the region of attenuated thickening. To determine whether adventitial fibroblasts contributed to this attenuation, AT1a receptors in fibroblasts were depleted using S100A4 driven Cre. Similar to enolase 2-Cre, Ang II-induced medial thickening was attenuated in the ascending, but not the descending aorta. Lineage tracking demonstrated an increase of S100A4-LacZ positive cells in the media of the ascending region during Ang II infusion. CONCLUSIONS: AT1a receptor depletion in fibroblasts attenuates Ang II-induced medial hyperplasia in the ascending aorta. PMID- 26160958 TI - Effects of Extended-Release Nicotinic Acid on Apolipoprotein (a) Kinetics in Hypertriglyceridemic Patients. AB - OBJECTIVE: To determine the mechanisms by which extended-release nicotinic acid reduces circulating lipoprotein (a) concentrations in hypertriglyceridemic patients. APPROACH AND RESULTS: Eight nondiabetic, obese male subjects (aged 48+/ 12 years; body mass index, 31.2+/-1.8 kg/m(2)) with hypertriglyceridemia (triglycerides, 226+/-78 mg/dL) were enrolled in an 8 week, double blind, placebo controlled cross-over study. At the end of each treatment phase, fasted subjects received a 10 umol/L per kg bolus injection of [5,5,5-(2)H3]-l-Leucine immediately followed by constant infusion of [5,5,5-(2)H3]-l-Leucine (10 umol L( 1) kg(-1) h(-1)) for 14 hours, and blood samples were collected. A liquid chromatography-tandem mass spectrometry method was used to study apolipoprotein (a) (Apo(a)) kinetics. The fractional catabolic rate of Apo(a) was calculated with a single compartmental model using the apolipoprotein B100 (ApoB100) containing very low density lipoprotein tracer enrichment as a precursor pool. Extended-release nicotinic acid decreased plasma triglycerides (-46%; P=0.023), raised high-density lipoprotein cholesterol (+20%; P=0.008), and decreased Apo(a) plasma concentrations (-20%; P=0.008). Extended-release nicotinic acid also decreased ApoB100 (22%; P=0.008) and proprotein convertase subtilisin/kexin type 9 (PCSK9, -29%; P=0.008) plasma concentrations. Apo(a) fractional catabolic rate and production rates were decreased by 37% (0.58+/-0.28 versus 0.36+/-0.19 pool/d; P=0.008) and 50% (1.4+/-0.8 versus 0.7+/-0.4 nmol/kg per day; P=0.008), respectively. CONCLUSIONS: Extended-release nicotinic acid treatment decreased Apo(a) plasma concentrations by 20%, production rates by 50%, and catabolism by 37%. ApoB100 and PCSK9 concentrations were also decreased by treatment, but no correlation was found with Apo(a) kinetic parameters. PMID- 26160959 TI - Improving Quality and Potency Testing for Umbilical Cord Blood: A New Perspective. AB - This article critically reviews current methods to test and characterize umbilical cord blood (UCB) for hematopoietic stem cell transplantation. These tests include total nucleated cell (TNC) count, viability, viable CD34-positive content, and the colony-forming unit assay. It is assumed that the data obtained are sufficient to perform a UCB stem cell transplant without actually determining the quality and potency of the stem cells responsible for engraftment. This assumption has led not only to a high graft failure rate attributed to low or lack of potency, but also to noncompliance with present statutes that require UCB stem cells to be of high quality and, indeed, potency for a transplant to be successful. New evidence now calls into question the quality of the data, based on the UCB processed TNC fraction because using this impure fraction masks and significantly underestimates the functionality of the stem cells in both the segment and the unit. It is proposed that UCB units should be processed to the mononuclear cell fraction and that new cost-effective technology that measures the quality and potency of UCB stem cells be implemented to achieve better practices in UCB testing. These changes would provide the transplant physician with the assurance that the stem cells will perform as intended and would reduce risk and increase safety and efficacy for the patient. SIGNIFICANCE: Current stem cell transplantation of umbilical cord blood cells requires testing that includes four basic parameters that do not determine whether the stem cells are of high quality, as required by the Stem Cell Therapeutic and Research Act of 2005. No cord blood units collected or transplanted so far have been tested for stem cell quality or potency. New scientific evidence calls into question cord blood processing and testing practices required by regulatory agencies and standards organizations. A new perspective is described that includes stem cell quality and potency testing that could reduce graft failure rates. PMID- 26160955 TI - Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association. PMID- 26160960 TI - Comparison of Different Cytokine Conditions Reveals Resveratrol as a New Molecule for Ex Vivo Cultivation of Cord Blood-Derived Hematopoietic Stem Cells. AB - Human cord blood (CB)-derived hematopoietic stem cells (HSCs) are an interesting source for HSC transplantation. However, the number of collected CB-HSCs is often too low for one transplantation; therefore, ex vivo expansion of CB-HSCs is desirable. Current expansion protocols are based on the use of cytokine combinations, including insulin-like growth factor-binding protein 2 (IGFBP2) and angiopoietin-like proteins, or combinations with "small molecules" such as stemregenin-1. The aim of our project was to compare the potential of different CB-HSC expansion strategies side-by-side by phenotypical analysis in vitro and serial engraftment properties in NOD/SCID/IL2rg-/- (NSG) immunodeficient mice. We further identified resveratrol, a naturally occurring polyphenol, as a new, alternative small molecule combined with cytokines to facilitate serum-free ex vivo expansion of human CB-HSCs. The cultivation in resveratrol preserved the CB HSC phenotype in vitro most efficiently and was ~2 times more potent than commonly used cytokine conditions (including stem cell factor, thrombopoietin, Fms-related tyrosine kinase 3 ligand, interleukin-6) and the recently established serum-free culture, including IGFBP2 and angiopoietin-like 5. Serial transplantation studies further confirmed resveratrol to support robust multilineage engraftment in primary and secondary NSG recipients. Therefore, our work proposes resveratrol as a new small molecule for improved ex vivo culture and modification of human HSCs based on an efficient ex vivo propagation of the HSC fate. SIGNIFICANCE: Human cord blood (CB)-derived hematopoietic stem cells (HSCs) are an important source for HSC transplantations but restricted in their usage because of their low numbers. In gene therapy, modifications of HSCs relies on their ex vivo modification without losing their stemness properties. Therefore, ex vivo cultivation and expansion of CB-HSCs is important for their effective application in HSC transplantation and gene therapy. Several promising protocols for serum-free cultivation of HSCs using different combinations of cytokines or so-called small molecules are described. A direct comparison was performed of three described serum-free cytokine conditions, demonstrating that the natural occurring polyphenol resveratrol is able to support ex vivo cultivation of CB-HSCs. The results show that resveratrol is an additional candidate for improving ex vivo cultures of HSCs for transplantation and gene therapeutic applications in the future. PMID- 26160961 TI - Improving the Post-Stroke Therapeutic Potency of Mesenchymal Multipotent Stromal Cells by Cocultivation With Cortical Neurons: The Role of Crosstalk Between Cells. AB - The goal of the present study was to maximally alleviate the negative impact of stroke by increasing the therapeutic potency of injected mesenchymal multipotent stromal cells (MMSCs). To pursue this goal, the intercellular communications of MMSCs and neuronal cells were studied in vitro. As a result of cocultivation of MMSCs and rat cortical neurons, we proved the existence of intercellular contacts providing transfer of cellular contents from one cell to another. We present evidence of intercellular exchange with fluorescent probes specifically occupied by cytosol with preferential transfer from neurons toward MMSCs. In contrast, we observed a reversed transfer of mitochondria (from MMSCs to neural cells). Intravenous injection of MMSCs in a postischemic period alleviated the pathological indexes of a stroke, expressed as a lower infarct volume in the brain and partial restoration of neurological status. Also, MMSCs after cocultivation with neurons demonstrated more profound neuroprotective effects than did unprimed MMSCs. The production of the brain-derived neurotrophic factor was slightly increased in MMSCs, and the factor itself was redistributed in these cells after cocultivation. The level of Miro1 responsible for intercellular traffic of mitochondria was increased in MMSCs after cocultivation. We conclude that the exchange by cellular compartments between neural and stem cells improves MMSCs' protective abilities for better rehabilitation after stroke. This could be used as an approach to enhance the therapeutic benefits of stem cell therapy to the damaged brain. SIGNIFICANCE: The idea of priming stem cells before practical use for clinical purposes was applied. Thus, cells were preconditioned by coculturing them with the targeted cells (i.e., neurons for the treatment of brain pathological features) before the transfusion of stem cells to the organism. Such priming improved the capacity of stem cells to treat stroke. Some additional minimal study will be required to develop a detailed protocol for coculturing followed by cell separation. PMID- 26160963 TI - Is thoracoscopic patent ductus arteriosus closure superior to conventional surgery? AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether thoracoscopic patent ductus arteriosus (PDA) closure is superior to conventional surgery. Altogether 821 papers were found using the reported search, 11 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Eleven studies included in the analysis consisted of two prospective and three retrospective, non-randomized studies and six case series. Four included studies focused only on preterm infants, three studies enrolled neonates and the other four analysed all age groups from neonates to older children or young adults. There were no differences in mortality between video-assisted thoracoscopic surgery (VATS) and conventional surgery. Two studies suggested that VATS offers shorter operative times. Two papers observed shorter hospital stay, although the other two noted no significant difference. A large prospective trial found VATS to be associated with a lower number of postoperative complications in neonates and infants, whereas other studies suggested no significant differences in short-term postoperative complications. There is little evidence to suggest better musculoskeletal status and cosmesis in neonates following VATS. Conversion from thoracoscopy to thoracotomy described in six papers was seldom and it did not lead to any additional complications. All observational studies confirmed that both techniques are free from major adverse cardiovascular complications and these two techniques can be safely used in all patients qualified for surgical PDA closure. Two studies compared cost effectiveness between the two techniques; one of them described VATS as significantly more cost-efficient, whereas the other study observed no difference. However, it should be noted that data were provided from different countries and time periods. The results presented suggest that there are no significant differences in early clinical outcomes between VATS and thoracotomy in all age groups. However, where differences have been shown, such as pain, postoperative complications, length of hospital and ICU stay and cost, these favour the VATS approach. PMID- 26160964 TI - Transthoracic echocardiography for selection of tubular graft size in David reimplantation technique. AB - OBJECTIVES: Selection of tubular graft size during David reimplantation technique for aortic root dilatation is based on perioperative leaflet height measurements. The present study evaluated whether transthoracic echocardiography (TTE)-based algorithms may help in selecting the graft size preoperatively. METHODS: Thirty patients (52 +/- 11 years old, 73% men) who underwent David reimplantation technique were evaluated. The implanted graft size was based on the David's formula. Leaflet height [diameter = 1.1 * ((2 * 2/3 * leaflet height) + 2)), leaflet length (diameter = ((2 * 2/3 * leaflet length) + 2)] and leaflet area [diameter = 0.8 * ((2 * ?(total leaflet area/pi)) + 2)] TTE-derived formulas were retrospectively developed. The percentage of under- or oversized implanted grafts was calculated and the association between the adequacy of graft sizing using TTE derived formulas and the incidence of residual aortic regurgitation (AR) was evaluated retrospectively. RESULTS: The incidence of postoperative mild residual AR was 23%. The true diameter of the inplanted graft was oversized based on leaflet height in 15 (50%) patients, based on leaflet length in 13 (43%) patients and based on leaflet area TTE-derived formula in 11 (37%) patients. The incidence of mild AR was significantly lower in undersized grafts compared with oversized grafts based on leaflet length TTE-derived formula (6 vs 46%, P = 0.032) and leaflet area TTE-derived formula (5 vs 55%, P = 0.009). CONCLUSIONS: In patients undergoing David reimplantation technique, grafts considered undersized according to the leaflet length or leaflet area TTE-derived formula were associated with less incidence of residual AR than patients with oversized grafts. PMID- 26160962 TI - Identification of Regions in the Receiver Domain of the ETHYLENE RESPONSE1 Ethylene Receptor of Arabidopsis Important for Functional Divergence. AB - Ethylene influences the growth and development of Arabidopsis (Arabidopsis thaliana) via five receptor isoforms. However, the ETHYLENE RESPONSE1 (ETR1) ethylene receptor has unique, and sometimes contrasting, roles from the other receptor isoforms. Prior research indicates that the receiver domain of ETR1 is important for some of these noncanonical roles. We determined that the ETR1 receiver domain is not needed for ETR1's predominant role in mediating responses to the ethylene antagonist, silver. To understand the structure-function relationship underlying the unique roles of the ETR1 receiver domain in the control of specific traits, we performed alanine-scanning mutagenesis. We chose amino acids that are poorly conserved and are in regions predicted to have altered tertiary structure compared with the receiver domains of the other two receptors that contain a receiver domain, ETR2 and ETHYLENE INSENSITIVE4. The effects of these mutants on various phenotypes were examined in transgenic, receptor-deficient Arabidopsis plants. Some traits, such as growth in air and growth recovery after the removal of ethylene, were unaffected by these mutations. By contrast, three mutations on one surface of the receiver domain rendered the transgene unable to rescue ethylene-stimulated nutations. Additionally, several mutations on another surface altered germination on salt. Some of these mutations conferred hyperfunctionality to ETR1 in the context of seed germination on salt, but not for other traits, that correlated with increased responsiveness to abscisic acid. Thus, the ETR1 receiver domain has multiple functions where different surfaces are involved in the control of different traits. Models are discussed for these observations. PMID- 26160965 TI - Perioperative change in creatinine following cardiac surgery with cardiopulmonary bypass is useful in predicting acute kidney injury: a single-centre retrospective cohort study. AB - OBJECTIVES: Acute kidney injury is common following cardiac surgery. Experimental models of acute kidney injury suggest that successful therapy should be implemented within 24-48 h of renal injury. However, it is difficult to detect acute kidney injury shortly after cardiac surgery, because creatinine concentration is diluted by cardiopulmonary bypass. We hypothesized that, following cardiopulmonary bypass, creatinine reduction ratios would correlate with haematocrit reduction ratios and would be associated with the incidence of acute kidney injury. METHODS: We collected demographic and blood test data from consecutive patients (n = 1137) who had undergone cardiac surgery with cardiopulmonary bypass. The creatinine reduction ratio was calculated as follows: (preoperative creatinine-postoperative creatinine)/preoperative creatinine. Patients were assigned to either of two groups. The first group (Group 1) was used to determine the threshold for acute kidney injury, and the second group (Group 2) was used to assess diagnostic performance. Acute kidney injury was defined as an increase in serum creatinine level >0.3 mg/dl or >150% from baseline. RESULTS: The incidence of acute kidney injury was 14.5% (79/545) in Group 1 and 15.5% (92/592) in Group 2. Postoperatively, creatinine concentration correlated strongly with haematocrit concentration (Pearson's r(2): 0.91). In Group 1, the area under the receiver operating characteristic curve, sensitivity and specificity were 0.71, 64.1 and 66.4%, respectively, for creatinine reduction ratios of <20%. In Group 2, the odds ratio, positive predictive value, negative predictive value and relative risk for creatinine reduction ratio performance were 4.3 (95% confidence interval 2.6-7.0), 0.27 (0.21-0.32), 0.92 (0.89-0.95) and 3.42 (2.22-5.27), respectively. CONCLUSIONS: The creatinine reduction ratio may be associated with perioperative renal injury. Therefore, it is a good diagnostic indicator with high performance, and may be useful in detecting acute kidney injury at an earlier stage relative to conventional means. In addition, using creatinine reduction ratios in this manner is financially feasible. PMID- 26160966 TI - Influence of voluntary standards and design modifications on trampoline injury in Victoria, Australia. AB - PURPOSE: To examine the influence of the voluntary Australian trampoline standard (AS 4989-2006) and market-driven design modifications on relevant trampoline injuries. METHODS: Trend and intervention analysis on frequencies and proportions of hospital-treated trampoline-related injury in Victoria, Australia, extracted from the Victorian Emergency Minimum Dataset from 1 July 1999 to 30 June 2013. The injuries relevant to the AS were contact with spring and frame, and multiple user injury. Falls from trampolines were relevant for netted trampolines, a market-driven modification. RESULTS: Frequency of all trampoline injuries increased by 11.4% (95% CI 10.0% to 11.7%) on average each year. Spring and frame, and fall injuries increased to a lesser extent (8.7%, 95% CI 6.9% to 9.8% and 7.3%, 95% CI 5.8% to 8.3%, respectively). Multiple-user injuries increased by 21.0% (95% CI 16.3% to 21.9%). As a proportion of all trampoline injuries, spring and frame injury and falls injury decreased, while multiple-user injuries increased. The intervention analysis showed no significant change in spring and frame injuries associated with the AS (p=0.17). A significant increase was found for multiple-user injuries (p=0.01), in particular for the 0-year to 4-year age group (p<0.0001), post 2007. CONCLUSIONS: There was little evidence for an effect of the voluntary standard on spring and frame injury and none for multiple-user injury. Netted trampolines appear to be associated with a decrease in falls from trampolines but an increase in injuries to multiple users. A mandated trampoline safety standard and a safety campaign including warnings about multiple users is recommended. Continued monitoring of injury data will be required. PMID- 26160967 TI - Emergency Department Return Visits Resulting in Admission: Do They Reflect Quality of Care? AB - Prior studies have suggested that emergency department (ED) return visits resulting in admission may be a more robust quality indicator than all 72-hour returns. The objective was to evaluate factors that contribute to admission within 72 hours of ED discharge. Each return visit resulting in admission was independently reviewed by 3 physicians. Analysis was by descriptive statistics. Of 45 071 ED discharges, 4.1% returned within 72 hours; 0.96% returned for related reasons and were admitted to wards (91.2%), intensive care units (6.5%), or operating rooms (1.2%). Management was acceptable in 92.6%, suboptimal in 7.4%. Admissions were illness (94.9%), patient (1.6%), and physician related (3.5%). Almost all admissions within 72 hours after ED discharge are illness related, including all intensive care unit admissions and the majority of operating room admissions. Deficiencies in ED care are rarely the reason for admission on return. ED return visits resulting in admission may not be reflective of ED quality of care. PMID- 26160968 TI - Transplantation-Associated Thrombotic Microangiopathy in Patients Treated With Sirolimus and Cyclosporine as Salvage Therapy for Graft-Versus-Host Disease. AB - BACKGROUND: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a rare complication of hematopoietic stem cell transplantation. Because sirolimus (SIR) and calcineurin inhibitor-either cyclosporine (CsA) or tacrolimus-have become more common as graft-versus-host disease (GVHD) prophylaxis, we are witnessing a higher frequency of this complication. OBJECTIVE: To analyze the incidence, timing, and management of TA-TMA in patients who received the combination of CsA and SIR as therapy for uncontrolled GVHD in one single center. METHODS: This was a retrospective analysis from February 2002 to June 2014 of the combination of SIR and CsA as salvage therapy in 61 patients with treatment refractory or relapsed acute GVHD (n = 24) or chronic GVHD (n = 37) in a tertiary hospital. RESULTS: A total of 61 patients received CsA and SIR as salvage therapy for acute (n = 16), late acute (n = 8), overlap syndrome (n = 22), or classic chronic (n = 15) GVHD. We identified 13 patients with TA-TMA (21.3%), and the status of GVHD was active in 11 of 13 patients. Only 1 patient showed high CsA levels, and 6 of 13 patients had very high concentrations of SIR in blood. We used an enzyme inducer in 6 patients, which proved effective in 3. Overall survival for TA-TMA patients was inferior compared to that for non TA-TMA patients at 12 months (42.9% vs 51.9%) and 24 months (34.3% vs 49.1%), although this difference was not significant. CONCLUSION: Prompt identification and good management of TA-TMA, with better control of GVHD, may contribute to a decrease in patient mortality that would result from this complication. PMID- 26160969 TI - Medication Discontinuation in Patients After Discharge From a Psychiatric Hospital. AB - BACKGROUND: Patients discharged from psychiatric hospitals may be at risk for intentional or unintentional discontinuation of their medication. OBJECTIVE: To describe and assess the discontinuation of, and changes to, psychiatric and/or somatic medication in patients after discharge from psychiatric hospitals. METHODS: A retrospective follow-up study was conducted in patients discharged from 4 psychiatric hospitals in The Netherlands between 2006 and 2009. Patients' medication use during the last 2 days of hospitalization was compared with medication dispensed during the 3 months following discharge. Changes in psychiatric and somatic medication were investigated and defined as medication discontinuation, start, or switch. Patients were classified as continuing users, when there were no changes to the medication after discharge. Relative risks with 95% confidence intervals to measure differences in discontinuation were estimated using Cox regression analysis. RESULTS: This study included 1324 patients, 69.8% of whom discontinued medication, and 9.7% switched one or more medications. Nearly half (47.4%) of all patients started a medication other than that dispensed during the last 2 days of hospitalization, and 13.7% of all patients experienced no changes to their medication regimen. Approximately 40% of the patients discontinued one or more medications for chronic conditions. From these, 68% discontinued psychiatric medications and 49.4% discontinued somatic medications. A quarter (25.2%) of the 644 patients discontinued using antipsychotics. More than a quarter (28.4%) of the 292 patients using medications for cardiovascular problems discontinued. Patients using as-needed medication prior to discharge were more likely to discontinue their medication (relative risk = 1.85; 95% confidence interval = 1.55-2.20). CONCLUSIONS: Discharge from a psychiatric hospital led to medication discontinuation in approximately 70% of all patients. Approximately 40% of the patients discontinued medications for chronic conditions. Discontinuation of somatic medication was more frequent than discontinuation of psychiatric medication, and risk of discontinuation was lower for patients with depressive and anxiety disorders. Although medication discontinuation can be deliberate it is alarming that a quarter of our patients using antipsychotics and cardiovascular medications discontinued their use, both of which are meant for chronic conditions. PMID- 26160970 TI - Ceftolozane/Tazobactam: A New Cephalosporin and beta-Lactamase Inhibitor Combination. AB - OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of ceftolozane/tazobactam, a new antipseudomonal cephalosporin combined with a well established beta-lactamase inhibitor. DATA SOURCES: A literature search through clinicaltrials.gov and PubMed was conducted (January 2007-May 2015) using the search terms ceftolozane, ceftolozane/tazobactam, FR264205, CXA-101/tazobactam, and CXA-201. References from retrieved articles and abstracts presented at recent meetings were reviewed to identify additional material. The prescribing information was also reviewed. STUDY SELECTION AND DATA EXTRACTION: Preclinical data as well as phase 1, 2, and 3 studies published in English were evaluated. DATA SYNTHESIS: Ceftolozane/tazobactam displays enhanced potency against Pseudomonas aeruginosa in vitro. Clinical trials have shown that ceftolozane/tazobactam is noninferior to levofloxacin for the treatment of complicated urinary tract infections (76.9% vs 68.4%, 95% CI = 2.3-14.6) and when used in combination with metronidazole is noninferior to meropenem for the treatment of complicated intra-abdominal infections (83% vs 87.3%, 95% CI = -8.91 to 0.54). An alternate antibiotic should be considered in patients who have a severe beta-lactam allergy or an estimated creatinine clearance between 30 and 50 mL/min. Ceftolozane/tazobactam is well tolerated, with few drug interactions and no effects on the cytochrome P450 system. CONCLUSIONS: In an era of increasing resistance to antimicrobials, ceftolozane/tazobactam provides clinicians with an additional treatment option for infections caused by multidrug-resistant Gram negative organisms, including extended-spectrum beta-lactamase-producing bacteria and Pseudomonas aeruginosa. PMID- 26160971 TI - Successful Treatment of Clopidogrel Hypersensitivity With a Seven-Day Taper of Oral Corticosteroid. PMID- 26160972 TI - Late-Occurring Vancomycin-Associated Acute Kidney Injury in Children Receiving Prolonged Therapy. AB - BACKGROUND: Acute kidney injury (AKI) in patients receiving vancomycin has been associated with trough concentrations >=15 mg/L and longer therapy duration. The objective of this study was to determine the incidence and factors associated with late AKI in children receiving >=8 days of vancomycin therapy. METHODS: Children aged 30 days to 17 years who were admitted to our institution and received intravenous vancomycin for at least 8 days during January to December of 2007 and 2010 and had a suspected or proven gram-positive infection were included. Late AKI was categorized as AKI occurring after the first 7 days of therapy and within 48 hours following vancomycin discontinuation. The primary outcome was incidence of late AKI as determined by modified pRIFLE criteria. RESULTS: One-hundred sixty-seven patients were included, with a median (interquartile range) age (years) and weight (kg) of 2 (1-7) and 12.5 (8.9-23.8). Late AKI was identified in 12.6% (21/167). A higher percentage of late AKI patients received concomitant treatment with intravenous acyclovir, amphotericin products, or piperacillin-tazobactam. Age <1 year was the only factor independently associated with late AKI development (odds ratio = 4.4; 95% confidence interval = 1.3-15.4). CONCLUSIONS: Late AKI occurred in nearly 13% of children receiving >=8 days of vancomycin therapy. This study suggests that vancomycin trough concentrations are not associated with late AKI, but that age <1 year and concomitant administration of certain nephrotoxins may be factors associated with increased risk. PMID- 26160973 TI - Risk Factors Exacerbating Hand-Foot Skin Reaction Induced by Capecitabine plus Oxaliplatin with or without Bevacizumab Therapy. AB - BACKGROUND: Capecitabine plus oxaliplatin (CapeOx) +/- bevacizumab therapy is associated with a high incidence of hand-foot skin reaction (HFSR), hindering treatment. However, timing of onset and risk factors remain unclear. OBJECTIVE: This study examined the development of HFSR and risk factors for its exacerbation to a serious condition in CapeOx +/- bevacizumab therapy. METHODS: We retrospectively examined patients with colorectal cancer receiving CapeOx +/- bevacizumab therapy between October 1, 2009, and March 31, 2012. The observation period was defined as lasting until completion of 8 cycles. The relationship between cumulative dose of capecitabine and cumulative proportion of patients developing HFSR was evaluated by Kaplan-Meier methods. Risk factors for exacerbation of HFSR to a serious condition were assessed by multiple logistic regression. RESULTS: Data for 203 patients were analyzed. For patients treated at cumulative capecitabine doses of 100 000 mg/m(2) and 200 000 mg/m(2), Grade 1 HFSR occurred in >=80% and >=90%, respectively, and moderate-to-severe HFSR (Grade 2+) occurred in >=10% and >=20%, respectively. Multivariate analysis showed significant associations with diabetes (odds ratio [OR] = 4.79; 95% confidence interval [CI] = 1.86-12.34; P = 0.001), concomitant use of bevacizumab (OR = 6.01; 95% CI = 2.20-16.41; P = 0.001), history of fluorinated pyrimidine administration (OR = 2.42; 95% CI = 1.10-5.33; P = 0.027), and early onset (within 21 days) of Grade 1 HFSR (OR = 3.78; 95% CI = 1.64-8.70; P = 0.001). CONCLUSIONS: HFSR in CapeOx therapy is a cumulative toxicity and risk of exacerbation to a serious condition increases with diabetes, concomitant use of bevacizumab, history of fluorinated pyrimidine administration, and onset of Grade 1 HFSR within 21 days. PMID- 26160974 TI - Clinical validation of three short forms of the Dutch Wechsler Memory Scale Fourth Edition (WMS-IV-NL) in a mixed clinical sample. AB - The reliability and validity of three short forms of the Dutch version of the Wechsler Memory Scale-Fourth Edition (WMS-IV-NL) were evaluated in a mixed clinical sample of 235 patients. The short forms were based on the WMS-IV Flexible Approach, that is, a 3-subtest combination (Older Adult Battery for Adults) and two 2-subtest combinations (Logical Memory and Visual Reproduction and Logical Memory and Designs), which can be used to estimate the Immediate, Delayed, Auditory and Visual Memory Indices. All short forms showed good reliability coefficients. As expected, for adults (16-69 years old) the 3-subtest short form was consistently more accurate (predictive accuracy ranged from 73% to 100%) than both 2-subtest short forms (range = 61%-80%). Furthermore, for older adults (65-90 years old), the predictive accuracy of the 2-subtest short form ranged from 75% to 100%. These results suggest that caution is warranted when using the WMS-IV-NL Flexible Approach short forms to estimate all four indices. PMID- 26160975 TI - Understanding children: Assessing school-aged children's self-protective attachment strategies. PMID- 26160976 TI - Validation of the School-age Assessment of Attachment in a short-term longitudinal study. AB - This study tested the validity of the School-aged Assessment of Attachment (SAA) in terms of matches from the well-validated Preschool Assessment of Attachment (PAA) to the SAA 6 months later. It also addressed validity in terms of mental health services and measures of stress, depression and anxiety. HYPOTHESES: Children's SAA classifications were predicted to match their 6 months' previous PAA classifications and indicators of maternal, child and family stress. The study used a two-group comparative design, involving normative and clinical children and their mothers. METHOD: The participants were 50 children between 5.5 and 5.9 years of age. Each child participated with his or her mother in a PAA, and then 6 months later each child responded to the SAA story cards as well as self-report assessments of stress, anxiety and depression. RESULTS: Concordance of A, B, C and A/C attachment classifications was found between the PAA and SAA in 34 of 48 children. There was a strong relation between referral status (clinical or normative) and both PAA and SAA attachment classifications. In every non-matching case, a normative child had an attachment classification indicative of risk, indicating that the direction of errors was false positives as opposed to false negatives. CONCLUSIONS: This evidence supports the validity and clinical utility of the SAA. PMID- 26160977 TI - Validity of the School-age Assessment of Attachment for moderate-risk, rural early adolescents. AB - INTRODUCTION: This study provides evidence of validity of the School-age Assessment of Attachment (SAA) through longitudinal comparison with the Preschool Assessment of Attachment (PAA) and with concurrent attachment assessments and measures of risk and parenting. Determining which assessment had the greatest validity with this moderate-risk sample would be of benefit to those working with troubled young people and their families. HYPOTHESES: Children's SAA classifications were expected to correspond to their PAA, a behavioral attachment assessment, parenting, and risk. An attachment questionnaire was predicted to not accurately indicate children's risk status. DESIGN: The design was an 8-year longitudinal follow-up of rural Appalachian American preschoolers. METHOD: The participants were 21 children and their caregivers. The PAA was completed at age 4. The SAA, a self-report questionnaire, and a parent-child conflict resolution task were completed at age 12. Parents completed assessments of depression, trauma, stress, and perceptions of helplessness. RESULTS: The PAA was related to the SAA and the dyadic behavioral task. The SAA was consistently associated with measures of parenting and family risk. The attachment questionnaire performed poorly for children with higher risk status, suggesting more (not less) sensitive and responsive parenting. PMID- 26160979 TI - Corrigendum. AB - CORRIGENDUM: Nonsuicidal self-injury in an adolescent population in Singapore AUTHORS: : Augustine CY Tan, Mark C Rehfuss, Elisabeth C Suarez and Agatha Parks SavagePublished in Clinical Child Psychology and Psychiatry 2014, Volume 19 Issue 1, pages 58-76, DOI: 10.1177/1359104512467273.Link: http://ccp.sagepub.com/content/19/1/58.full.pdf+htmlIn the aforementioned article. the corresponding author (Augustine CY Tan) missed to include the below Acknowledgement statement:Authors would like to acknowledge the helpful contributions of Dr. Ong Say How of the Institute of Mental Health (IMH), Singapore, towards this study. PMID- 26160978 TI - The attachment of prematurely born children at school age: A pilot study. AB - This prospective longitudinal study compared the psychological development and patterns of attachment of 20 prematurely born children and 20 full-term children at 7 years of age. The School-age Assessment of Attachment (SAA) was used, and hypotheses and interpretation of the findings were drawn from the Dynamic Maturational Model of Attachment and Adaptation (DMM). Significant differences between prematurely born and full-term children were found: 10% versus 0% at "high" risk, 55% versus 25% at "moderate" risk, and 35% versus 75% at "low" risk. There were no differences in the percentage of psychological trauma between samples, but there was a difference in the types of experiences leading to trauma. For prematurely born children, it was most often illness, whereas for full-term children, it was family problems. We discuss the implications for clinicians. PMID- 26160980 TI - Brains, brawn and sociality: a hyaena's tale. AB - Theoretically intelligence should evolve to help animals solve specific types of problems posed by the environment, but it remains unclear how environmental complexity or novelty facilitates the evolutionary enhancement of cognitive abilities, or whether domain-general intelligence can evolve in response to domain-specific selection pressures. The social complexity hypothesis, which posits that intelligence evolved to cope with the labile behaviour of conspecific group-mates, has been strongly supported by work on the sociocognitive abilities of primates and other animals. Here we review the remarkable convergence in social complexity between cercopithecine primates and spotted hyaenas, and describe our tests of predictions of the social complexity hypothesis in regard to both cognition and brain size in hyaenas. Behavioural data indicate that there has been remarkable convergence between primates and hyaenas with respect to their abilities in the domain of social cognition. Furthermore, within the family Hyaenidae, our data suggest that social complexity might have contributed to enlargement of the frontal cortex. However, social complexity failed to predict either brain volume or frontal cortex volume in a larger array of mammalian carnivores. To address the question of whether or not social complexity might be able to explain the evolution of domain-general intelligence as well as social cognition in particular, we presented simple puzzle boxes, baited with food and scaled to accommodate body size, to members of 39 carnivore species housed in zoos and found that species with larger brains relative to their body mass were more innovative and more successful at opening the boxes. However, social complexity failed to predict success in solving this problem. Overall our work suggests that, although social complexity enhances social cognition, there are no unambiguous causal links between social complexity and either brain size or performance in problem-solving tasks outside the social domain in mammalian carnivores. PMID- 26160981 TI - Spatial and Seasonal Diversity of Wild Food Plants in Home Gardens of Northeast Thailand1. AB - Wild food plants (WFPs) are major components of tropical home gardens, constituting an important resource for poor farmers. The spatial and seasonal diversity of WFPs was analyzed across multi-species spatial configurations occurring within home gardens in a rice farming village in northeast Thailand. Data were collected in 77 sampling sites corresponding to five different home garden spatial configurations, namely fenced plot, fenced plot margin, yard, home garden boundary, and pot. Absolute abundance and frequency of occurrence were quantified per individual WFP species in both dry and rainy seasons, and data on additional uses (besides food) were collected through focus group discussions for each WFP species. A total of 20 species corresponding to 13 botanical families were reported. Results show that species abundance and frequency of occurrence varied seasonally and spatially within home gardens. Diversity, as observed in the analysis of Shannon and Simpson diversity indexes, also differed seasonally and across different spatial configurations. Home gardens showed higher diversity in the dry season because of the presence of human management. Ninety-five percent of the WFP species presented additional uses, with nine different types of uses in total. Finally, as this study demonstrates, the results on both the spatial and seasonal diversity of WFPs over different spatial configurations comprise a new perspective in home garden research by providing new understandings about their composition and management. PMID- 26160982 TI - Effects of Detector Thickness on Geometric Sensitivity and Event Positioning Errors in the Rectangular PET/X Scanner. AB - We used simulations to investigate the relationship between sensitivity and spatial resolution as a function of crystal thickness in a rectangular PET scanner intended for quantitative assessment of breast cancers. The system had two 20 * 15-cm2 and two 10 * 15-cm2 flat detectors forming a box, with the larger detectors separated by 4 or 8 cm. Depth-of-interaction (DOI) resolution was modeled as a function of crystal thickness based on prior measurements. Spatial resolution was evaluated independent of image reconstruction by deriving and validating a surrogate metric from list-mode data (dFWHM). When increasing crystal thickness from 5 to 40 mm, and without using DOI information, the dFWHM for a centered point source increased from 0.72 to 1.6 mm. Including DOI information improved dFWHM by 12% and 27% for 5- and 40-mm-thick crystals, respectively. For a point source in the corner of the FOV, use of DOI information improved dFWHM by 20% (5-mm crystal) and 44% (40-mm crystal). Sensitivity was 7.7% for 10-mm-thick crystals (8-cm object). Increasing crystal thickness on the smaller side detectors from 10 to 20 mm (keeping 10-mm crystals on the larger detectors) boosted sensitivity by 24% (relative) and degraded dFWHM by only ~3%/8% with/without DOI information. The benefits of measuring DOI must be evaluated in terms of the intended clinical task of assessing tracer uptake in small lesions. Increasing crystal thickness on the smaller side detectors provides substantial sensitivity increase with minimal accompanying loss in resolution. PMID- 26160983 TI - High-Resolution Anamorphic SPECT Imaging. AB - We have developed a gamma-ray imaging system that combines a high-resolution silicon detector with two sets of movable, half-keel-edged copper-tungsten blades configured as crossed slits. These apertures can be positioned independently between the object and detector, producing an anamorphic image in which the axial and transaxial magnifications are not constrained to be equal. The detector is a 60 mm * 60 mm, one-millimeter-thick, one-megapixel silicon double-sided strip detector with a strip pitch of 59 MUm. The flexible nature of this system allows the application of adaptive imaging techniques. We present system details; calibration, acquisition, and reconstruction methods; and imaging results. PMID- 26160984 TI - Fisher Information Analysis of Depth-of-Interaction Estimation in Double-Sided Strip Detectors. AB - In very-high-spatial-resolution gamma-ray imaging applications, such as preclinical PET and SPECT, estimation of 3D interaction location inside the detector crystal can be used to minimize parallax error in the imaging system. In this work, we investigate the effect of bias voltage setting on depth-of interaction (DOI) estimates for a semiconductor detector with a double-sided strip geometry. We first examine the statistical properties of the signals and develop expressions for likelihoods for given gamma-ray interaction positions. We use Fisher Information to quantify how well (in terms of variance) the measured signals can be used for DOI estimation with different bias-voltage settings. We performed measurements of detector response versus 3D position as a function of applied bias voltage by scanning with highly collimated synchrotron radiation at the Advanced Photon Source at Argonne National Laboratory. Experimental and theoretical results show that the optimum bias setting depends on whether or not the estimated event position will include the depth of interaction. We also found that for this detector geometry, the z-resolution changes with depth. PMID- 26160985 TI - Revealing concealable stigmatized identities: The impact of disclosure motivations and positive first disclosure experiences on fear of disclosure and well-being. AB - People who live with concealable stigmatized identities face complex decisions regarding disclosure. In the current work, we examine how people's motivations for disclosing a concealable stigmatized identity for the first time affect the quality of their first disclosure experiences and how these experiences, in turn, affect current well-being. Specifically, we found that people who disclosed for ecosystem, or other-focused, reasons report more positive first disclosure experiences which, in turn, were related to higher current self-esteem. Analyses suggest that one reason why this first disclosure experience is related to current well-being is because positive first disclosure experiences may serve to lessen chronic fear of disclosure. Overall, these results highlight the importance of motivational antecedents for disclosure in impacting well-being and suggest that positive first disclosure experiences may have psychological benefits over time because they increase level of trust in others. PMID- 26160986 TI - Low EphA7 Expression Correlated with Lymph Node Metastasis and Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma. AB - As a member of the Eph family of receptor tyrosine kinases, EphA7 plays an important role in cancer. However, the expression and significance of Eph receptors in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we detected the expression of EphA7 by immunohistochemistry in a sample of 352 patients with ESCC, and aimed to investigate the expression status of EphA7 in ESCC and its impact on prognosis. The results showed that low EphA7 expression significantly correlated with lymph node metastases (N0: 29%; N1: 64%. p<0.001), poor degree of tumor differentiation (G1: 31%; G2: 49%; G3: 58%. p=0.009) and pTNM staging (I+II: 33%; III+IV: 58%. p<0.001). Furthermore, in a combined analysis, patients with low EphA7-expressing tumors showed a shorter overall survival than those with high expression, resulting in a five-year overall survival rate of 47.4% vs. 52.6%, respectively (p=0.016). Consequently, patients with a low EphA7 expression have poorer prognosis in ESCC compared with those manifesting high expression. PMID- 26160987 TI - Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice. AB - Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 MUg of a recombinant human KGF (rhKGF) expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema. PMID- 26160988 TI - Hertwig's Epithelial Root Sheath Fate during Initial Cellular Cementogenesis in Rat Molars. AB - To elucidate the fate of the epithelial root sheath during initial cellular cementogenesis, we examined developing maxillary first molars of rats by immunohistochemistry for keratin, vimentin, and tissue non-specific alkaline phosphatase (TNALP) and by TdT-mediated dUTP nick end labeling (TUNEL). The advancing root end was divided into three sections, which follow three distinct stages of initial cellular cementogenesis: section 1, where the epithelial sheath is intact; section 2, where the epithelial sheath becomes fragmented; and section 3, where initial cellular cementogenesis begins. After fragmentation of the epithelial sheath, many keratin-positive epithelial sheath cells were embedded in the rapidly growing cellular cementum. A few unembedded epithelial cells located on the cementum surface. Dental follicle cells, precementoblasts, and cementoblasts showed immunoreactivity for vimentin and TNALP. In all three sections, there were virtually no cells possessing double immunoreactivity for vimentin-keratin or TNALP-keratin and only embedded epithelial cells showed TUNEL reactivity. Taken together, these findings suggest that: (1) epithelial sheath cells divide into two groups; one group is embedded in the cementum and thereafter dies by apoptosis, and the other survives on the cementum surface as epithelial cell rests of Malassez; and (2) epithelial sheath cells do not undergo epithelial-mesenchymal transition during initial cellular cementogenesis. PMID- 26160989 TI - Efficacy and well-being in rural north India: The role of social identification with a large-scale community identity. AB - Identifying with a group can contribute to a sense of well-being. The mechanisms involved are diverse: social identification with a group can impact individuals' beliefs about issues such as their connections with others, the availability of social support, the meaningfulness of existence, and the continuity of their identity. Yet, there seems to be a common theme to these mechanisms: identification with a group encourages the belief that one can cope with the stressors one faces (which is associated with better well-being). Our research investigated the relationship between identification, beliefs about coping, and well-being in a survey (N = 792) administered in rural North India. Using structural equation modelling, we found that social identification as a Hindu had positive and indirect associations with three measures of well-being through the belief that one can cope with everyday stressors. We also found residual associations between participants' social identification as a Hindu and two measures of well-being in which higher identification was associated with poorer well-being. We discuss these findings and their implication for understanding the relationship between social identification (especially with large-scale group memberships) and well-being. We also discuss the application of social psychological theory developed in the urban West to rural north India. (c) 2014 The Authors. European Journal of Social Psychology published by John Wiley & Sons, Ltd. PMID- 26160990 TI - Odour Samples Degradation During Detention in Tedlar(r) Bags. AB - In indirect olfactometry analysis, to avoid condensation or adsorption processes during or storage of the sample, containers made of suitable materials should be used. Also, reaction between the chemicals during transport from the source of the odour to the research laboratory is an important process which can influence on examinations' results. Study included determination of the odour and compound concentrations of six gas mixtures. Gas samples were collected by silicone hoses into Tedlar(r) bags and tested by Nasal Ranger, SM-100 olfactometers and Photovac Voyager gas chromatograph. Time of keeping gas in bags was 78 h, and concentration of compounds was measured every hour, eight times per day. For benzene, acetone, 1,1-dichloroethylene, c-1,2-dichloroethylene, t-1,2 dichloroethylene, methyl ethyl ketone and vinyl chloride, 100 % decrease of concentration has been noticed within 78 h of holding in the bag. Average rate of loss of most compounds concentration was from 0.01 to 2.50 % for the first 30 h and from 0.35 to 18.50 % during the last 48 h of examination. Decreasing of odour concentration measured by Nasal Ranger (NR) in all series was between 0.00 and 4.98 % till 30 h, between 1.91 and 100 % in the last 48 h of test and between 1.61 and 100 % in 78 h. In case of odour concentration measured by SM, those values were, respectively, 1.26-4.93 %, 1.39-4.93 % and 2.40-3.18 %. Values of average rate of intensity decreasing were, respectively, 0.77-1.75 %, 2.36-4.67 % and 1.18-2.07 %. Statistically significant correlation coefficients for compound concentrations and intensity, odour concentration obtained by SM-100 as well as NR were, respectively, 0.55-0.97, 0.47-0.99 and 0.37-0.98. PMID- 26160991 TI - Evaluation of Dye Compounds' Decolorization Capacity of Selected H. haematococca and T. harzianum Strains by Principal Component Analysis (PCA). AB - The selected strains of microscopic fungi, Haematonectria haematococca (BwIII43, K37) and Trichoderma harzianum (BsIII33), decolorized the following monoathraquinone dyes with different efficiency: 0.03 % Alizarin Blue Black B, 0.01 % Carminic Acid, 0.01 % Poly R-478, and 0.2 % post-industrial lignin. The most effective was the removal of 0.03 % Alizarin Blue Black B (50-60 %) and 0.01 % Carminic Acid (55-85 %). The principal component analysis (PCA) method was applied to determine the main enzyme responsible for the biodecolorization process of the dye substrates and indicated that horseradish-type (HRP-like), lignin (LiP), and manganese-dependent (MnP) peroxidases were responsible for the decolorization of anthraquinone dyes by the strains tested. The participation of particular enzymes in the decolorization of monoanthraquinone dyes ranged from 44.48 to 51.70 % for 0.01 % Carminic Acid and from 38.46 to 61.12 % for Poly R 478. The highest precipitation in decolorization of these dyes showed HRP-like peroxidase, respectively, 54-74 and 70-95 %. The degree of decolorization of 0.2 % post-industrial lignin by the selected strains of H. haematococca and T. harzianum amounted to 58.20, 61.38, and 65.13 %, respectively. The rate of 0.2 % post-industrial lignin decolorization was conditioned by the activity of HRP-like (71-90 %) and LiP (87-94 %) peroxidases. PMID- 26160992 TI - Influence of Prior Knowledge on the Accuracy Limit of Parameter Estimation in Single-Molecule Fluorescence Microscopy. AB - In estimation theory, it is known that prior knowledge of parameters can improve the Cramer-Rao lower bound (CRLB). In this paper, we study the influence of prior knowledge on the CRLB of the estimates of the parameters that describe the trajectory of a moving object (single molecule). Since the CRLB is obtained from the inverse of the Fisher information matrix, we present a general expression of the Fisher information matrix in terms of the image function, the object trajectory and the prior knowledge matrix. Applying this expression to an object moving linearly in a two-dimensional (2D) plane with two distinct cases of prior knowledge, explicit CRLB expressions are derived. From these expressions, we show that the improvement in the CRLB of the parameter estimates is dependent on which parameters are known. PMID- 26160993 TI - Predicting Preterm Labour: Current Status and Future Prospects. AB - Preterm labour and birth are a major cause of perinatal morbidity and mortality. Despite modern advances in obstetric and neonatal management, the rate of preterm birth in the developed world is increasing. Yet even though numerous risk factors associated with preterm birth have been identified, the ability to accurately predict when labour will occur remains elusive, whether it is at a term or preterm gestation. In the latter case, this is likely due to the multifactorial aetiology of preterm labour wherein women may display different clinical presentations that lead to preterm birth. The discovery of novel biomarkers that could reliably identify women who will subsequently deliver preterm may allow for timely medical intervention and targeted therapeutic treatments aimed at improving maternal and fetal outcomes. Various body fluids including amniotic fluid, urine, saliva, blood (serum/plasma), and cervicovaginal fluid all provide a rich protein source of putative biochemical markers that may be causative or reflective of the various pathophysiological disorders of pregnancy, including preterm labour. This short review will highlight recent advances in the field of biomarker discovery and the utility of single and multiple biomarkers for the prediction of preterm birth in the absence of intra-amniotic infection. PMID- 26160994 TI - Experimental characterization of biphasic materials using rate-controlled Hertzian indentation. AB - This paper describes a new method, based on Hertzian biphasic theory (HBT), to characterize properties of biphasic materials with reduced time demands, increased surface sensitivity, and reduced computational demands compared to the current gold standards. Indentation experiments were conducted at a single location on a representative osteochondral plug to demonstrate and validate the HBT method against two gold standards, linear biphasic theory (LBT) and tension compression nonlinear biphasic theory (TCN). The 1) aggregate moduli, 2) permeability and 3) tensile moduli from HBT, LBT, and TCN were 1) HA =0.47, 0.47, and 0.40 MPa, 2) k=0.0026, 0.0014 and 0.0016mm4/Ns, and 3) Et =8.7, 0.46, and 10.3MPa, respectively. The results support the HBT method and encourage its use, especially in light of its practical advantages. PMID- 26160995 TI - Root-inhabiting fungi in alien plant species in relation to invasion status and soil chemical properties. AB - In order to recognize interactions between alien vascular plants and soil microorganisms and thus better understand the mechanisms of plant invasions, we examined the mycorrhizal status, arbuscular mycorrhizal fungi (AMF) colonization rate, arbuscular mycorrhiza (AM) morphology and presence of fungal root endophytes in 37 non-native species in Central Europe. We also studied the AMF diversity and chemical properties of soils from under these species. The plant and soil materials were collected in southern Poland. We found that 35 of the species formed AM and their mycorrhizal status depended on species identity. Thirty-three taxa had AM of Arum-type alone. Lycopersicon esculentum showed intermediate AM morphology and Eragrostis albensis developed both Arum and Paris. The mycelia of dark septate endophytes (DSE) were observed in 32 of the species, while sporangia of Olpidium spp. were found in the roots of 10. Thirteen common and worldwide occurring AMF species as well as three unidentified spore morphotypes were isolated from trap cultures established with the soils from under the plant species. Claroideoglomus claroideum, Funneliformis mosseae and Septoglomus constrictum were found the most frequently. The presence of root inhabiting fungi and the intensity of their colonization were not correlated with soil chemical properties, plant invasion status, their local abundance and habitat type. No relationships were also found between the presence of AMF, DSE and Olpidium spp. These suggest that other edaphic conditions, plant and fungal species identity or the abundance of these fungi in soils might have an impact on the occurrence and intensity of fungal root colonization in the plants under study. PMID- 26160996 TI - John W. Daly - An Appreciation. AB - John W. Daly was engaged in groundbreaking basic research for nearly 50 years at NIH in Bethesda, Maryland. A primary focus of his research included the discovery, structure elucidation, synthesis and pharmacology of alkaloids and other biologically active natural products. However, he earned further acclaim in other areas that included the investigation of the structure-activity relationships for agonists/antagonists at adenosine, adrenergic, histamine, serotonin, and acetylcholine receptors. In addition he was a pioneer in studies of the modulation and functional relationships for systems involving calcium, cyclic nucleotides, ion channels and phospholipids and in the mechanism of actions of caffeine and other xanthines. PMID- 26160997 TI - Transcranial Magnetic Stimulation to Address Mild Cognitive Impairment in the Elderly: A Randomized Controlled Study. AB - Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique with potential to improve memory. Mild cognitive impairment (MCI), which still lacks a specific therapy, is a clinical syndrome associated with increased risk of dementia. This study aims to assess the effects of high frequency repetitive TMS (HF rTMS) on everyday memory of the elderly with MCI. We conducted a double-blinded randomized sham-controlled trial using rTMS over the left dorsolateral prefrontal cortex (DLPFC). Thirty-four elderly outpatients meeting Petersen's MCI criteria were randomly assigned to receive 10 sessions of either active TMS or sham, 10 Hz rTMS at 110% of motor threshold, 2,000 pulses per session. Neuropsychological assessment at baseline, after the last session (10th) and at one-month follow-up, was applied. ANOVA on the primary efficacy measure, the Rivermead Behavioural Memory Test, revealed a significant group-by time interaction (p = 0.05), favoring the active group. The improvement was kept after one month. Other neuropsychological tests were heterogeneous. rTMS at 10 Hz enhanced everyday memory in elderly with MCI after 10 sessions. These findings suggest that rTMS might be effective as a therapy for MCI and probably a tool to delay deterioration. PMID- 26160998 TI - Personal Strengths and Health Related Quality of Life in Dementia Caregivers from Latin America. AB - The research literature has begun to demonstrate associations between personal strengths and enhanced psychosocial functioning of dementia caregivers, but these relationships have not been examined in the context of dementia caregivers in Latin America. The present study examined whether personal strengths, including resilience, optimism, and sense of coherence, were associated with mental and physical health related quality of life (HRQOL) in 130 dementia caregivers in Mexico and Argentina. Structural equation modeling found that the personal strengths collectively accounted for 58.4% of the variance in caregiver mental HRQOL, and resilience, sense of coherence, and optimism each had unique effects. In comparison, the personal strengths together accounted for 8.9% of the variance in caregiver physical HRQOL, and only sense of coherence yielded a unique effect. These results underscore the need to construct and disseminate empirically supported interventions based in part on important personal strengths, particularly sense of coherence, for this underrepresented group. PMID- 26160999 TI - Brain Signals of Face Processing as Revealed by Event-Related Potentials. AB - We analyze the functional significance of different event-related potentials (ERPs) as electrophysiological indices of face perception and face recognition, according to cognitive and neurofunctional models of face processing. Initially, the processing of faces seems to be supported by early extrastriate occipital cortices and revealed by modulations of the occipital P1. This early response is thought to reflect the detection of certain primary structural aspects indicating the presence grosso modo of a face within the visual field. The posterior temporal N170 is more sensitive to the detection of faces as complex-structured stimuli and, therefore, to the presence of its distinctive organizational characteristics prior to within-category identification. In turn, the relatively late and probably more rostrally generated N250r and N400-like responses might respectively indicate processes of access and retrieval of face-related information, which is stored in long-term memory (LTM). New methods of analysis of electrophysiological and neuroanatomical data, namely, dynamic causal modeling, single-trial and time-frequency analyses, are highly recommended to advance in the knowledge of those brain mechanisms concerning face processing. PMID- 26161001 TI - Normal Hearing Ability but Impaired Auditory Selective Attention Associated with Prediction of Response to Donepezil in Patients with Alzheimer's Disease. AB - BACKGROUND: Alzheimer's disease (AD) patients have a poor response to the voices of caregivers. After administration of donepezil, caregivers often find that patients respond more frequently, whereas they had previously pretended to be "deaf." We investigated whether auditory selective attention is associated with response to donepezil. METHODS: The subjects were40 AD patients, 20 elderly healthy controls (HCs), and 15 young HCs. Pure tone audiometry was conducted and an original Auditory Selective Attention (ASA) test was performed with a MoCA vigilance test. Reassessment of the AD group was performed after donepezil treatment for 3 months. RESULTS: Hearing level of the AD group was the same as that of the elderly HC group. However, ASA test scores decreased in the AD group and were correlated with the vigilance test scores. Donepezil responders (MMSE 3+) also showed improvement on the ASA test. At baseline, the responders had higher vigilance and lower ASA test scores. CONCLUSION: Contrary to the common view, AD patients had a similar level of hearing ability to healthy elderly. Auditory attention was impaired in AD patients, which suggests that unnecessary sounds should be avoided in nursing homes. Auditory selective attention is associated with response to donepezil in AD. PMID- 26161000 TI - Effects of Different Types of Cognitive Training on Cognitive Function, Brain Structure, and Driving Safety in Senior Daily Drivers: A Pilot Study. AB - BACKGROUND: Increasing proportion of the elderly in the driving population raises the importance of assuring their safety. We explored the effects of three different types of cognitive training on the cognitive function, brain structure, and driving safety of the elderly. METHODS: Thirty-seven healthy elderly daily drivers were randomly assigned to one of three training groups: Group V trained in a vehicle with a newly developed onboard cognitive training program, Group P trained with a similar program but on a personal computer, and Group C trained to solve a crossword puzzle. Before and after the 8-week training period, they underwent neuropsychological tests, structural brain magnetic resonance imaging, and driving safety tests. RESULTS: For cognitive function, only Group V showed significant improvements in processing speed and working memory. For driving safety, Group V showed significant improvements both in the driving aptitude test and in the on-road evaluations. Group P showed no significant improvements in either test, and Group C showed significant improvements in the driving aptitude but not in the on-road evaluations. CONCLUSION: The results support the effectiveness of the onboard training program in enhancing the elderly's abilities to drive safely and the potential advantages of a multimodal training approach. PMID- 26161002 TI - Isoflavone Attenuates the Caspase-1 and Caspase-3 Level in Cell Model of Parkinsonism. AB - The study has investigated the effect of isoflavone attenuates the caspase-1 and caspase-3 level in cell model of Parkinsonism. The subjects were PC12 cells. They were randomly divided into six groups: control, MPP(+) (250 MUmol/L), isoflavone (10 MUM), isoflavone (10 MUM) + MPP(+) (250 MUmol/L), Z-YVAD-CHO (10 nM) + MPP(+) group, and Z-DEVD-CHO (10 nM) + MPP(+) group. Cell viability was measured by MTT methods; the content of tyrosine hydroxylase was measured by immunocytochemistry method of avidinbiotin peroxidase complex; apoptosis ratio was measured by flow cytometry. The results showed that cell viability in the MPP(+) group was lower than in all other five groups. There was no difference in cell viability between isoflavone + MPP(+) and control group. Optical density of TH positive cells in isoflavone group was higher than in control, isoflavone + MPP(+), and MPP(+) only groups. The apoptosis ratio in the isoflavone + MPP(+) group and control group and the Z-YVAD-CHO + MPP(+) and Z-DEVD-CHO + MPP(+) group was similar, which was lower than in the MPP(+) group. The lowest apoptosis ratio was found in the isoflavone only group. PMID- 26161003 TI - Protective Effects of BDNF against C-Reactive Protein-Induced Inflammation in Women. AB - BACKGROUND: Since high sensitivity C-reactive protein (hsCRP) is predictive of cardiovascular events, it is important to examine the relationship between hsCRP and other inflammatory and oxidative stress markers linked to cardiovascular disease (CVD) etiology. Previously, we reported that hsCRP induces the oxidative stress adduct 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG) and that these markers are significantly associated in women. Recent data indicates that brain-derived neurotrophic factor (BDNF) may have a role in CVD. METHODS AND RESULTS: We examined BDNF levels in 3 groups of women that were age- and race-matched with low (<3 mg/L), mid (>3-20 mg/L), and high (>20 mg/L) hsCRP (n = 39 per group) and found a significant association between hsCRP, BDNF, and 8-oxodG. In African American females with high hsCRP, increases in BDNF were associated with decreased serum 8-oxodG. This was not the case in white women where high hsCRP was associated with high levels of BDNF and high levels of 8-oxodG. BDNF treatment of cells reduced CRP levels and inhibited CRP-induced DNA damage. CONCLUSION: We discovered an important relationship between hsCRP, 8-oxodG, and BDNF in women at hsCRP levels >3 mg/L. These data suggest that BDNF may have a protective role in counteracting the inflammatory effects of hsCRP. PMID- 26161004 TI - Chemerin15-Ameliorated Cardiac Ischemia-Reperfusion Injury Is Associated with the Induction of Alternatively Activated Macrophages. AB - Chemerin15 (C15), an endogenous anti-inflammatory component, inhibits the activity of neutrophils and macrophages through G protein-coupled receptor ChemR23; however, its role as well as functional mechanism in mouse myocardial ischemia/reperfusion (I/R) injury remains unknown. Methods. Sham or I/R operations were performed on C57BL/6J mice. The I/R mice received an injection of C15 immediately before reperfusion. Serum troponin T levels, infarct size, cardiomyocyte apoptosis, reactive oxygen species (ROS) production, and infiltration of neutrophils were assessed 24 h after reperfusion, while the macrophage phenotypes, macrophage infiltration, and inflammatory cytokine levels were assessed 48 h after reperfusion. Results. Compared with the control group, the C15-treated mice showed an obvious amelioration of I/R injury and displayed less ROS, accompanied by reduced neutrophil recruitment. C15 decreased the tumor necrosis factor- (TNF-) alpha and interleukin- (IL-) 6 levels and increased the IL-10 levels in the serum of the I/R mice, which suggested a suppressed inflammatory response that could be related to elevated alternatively activated M2 macrophages with characteristic skewed expression of M2 markers and inhibition of classically activated M1 marker expression. Conclusion. C15 may induce alternatively activated M2 macrophage polarization and suppress the inflammatory response to protect against myocardial I/R injury in mice. PMID- 26161005 TI - Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat. AB - OBJECTIVES: Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. MATERIAL AND METHOD: Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine?xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. RESULTS: In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. CONCLUSION: In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation. PMID- 26161006 TI - IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses. AB - Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL 33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)gamma and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis. PMID- 26161007 TI - Obesity Prevention and Treatment in School-aged Children, Adolescents, and Young Adults-Where Do We Go from Here? AB - The rise in the rate of obesity in school-aged children, adolescents, and young adults in the last 30 years is a clear healthcare crisis that needs to be addressed. Despite recent national reports in the United States highlighting positive downward trends in the rate of obesity in younger children, we are still faced with approximately 12.7 million children struggling with obesity. Given the immediate and long-term health consequences of obesity, much time and effort has been expended to address this epidemic. Yet, despite these efforts, we still only see limited, short-term success from most interventions. Without changes to how we address childhood obesity, we will continue to see inadequate improvements in the health of our children. Clinicians and researchers need to be lobbying for evidence-based policy changes, such as those identified by systems science, in order to improve the nation's health. PMID- 26161008 TI - A 2015 roadmap for the management of hepatitis C virus infections in Asia. AB - The prevalence of hepatitis C virus (HCV) in Asia is 0.5% to 4.7%, with three different genotypes predominating, depending on the geographic region: genotype 1b in East Asia, genotype 3 in South and Southeast Asia, and genotype 6 in Indochina. Official approval for direct-acting antiviral agents (DAAs) in Asia lags significantly behind that in the West, such that in most countries the mainstay of therapy is still pegylated interferon and ribavirin (PR). Because the interleukin-28B genetic variant, associated with a high sustained virologic response (SVR), is common in Asians, this treatment is still acceptable in Asian patients with HCV infections. A roadmap for HCV therapy that starts with PR and takes into account those DAAs already approved in some Asian countries can provide guidance as to the best strategies for management, particularly of genotype 1 and 3 infections, based on SVR rates. Sofosbuvir and PR are likely to be the initial therapies for genotype 1 and 3 disease, although in the former these drugs may be suboptimal in patients with cirrhosis (62% SVR) and the extension of treatment to 24 weeks may be required. For difficult to treat genotype 3 infections in treatment-experienced patients with cirrhosis, a combination of sofosbuvir and PR result in an 83% SVR and is, therefore, currently the optimal treatment regimen. Treatment failure is best avoided since data on rescue therapies for DAA failure are still incomplete. PMID- 26161010 TI - Hyponatremia in acute heart failure: a marker of poor condition or a mediator of poor outcome? PMID- 26161009 TI - Phenotype of asthma-chronic obstructive pulmonary disease overlap syndrome. AB - Many patients with asthma or chronic obstructive pulmonary disease (COPD) have overlapping characteristics of both diseases. By spirometric definition, patients with both fixed airflow obstruction (AO) and bronchodilator reversibility or fixed AO and bronchial hyperresponsiveness can be considered to have asthma-COPD overlap syndrome (ACOS). However, patients regarded to have ACOS by spirometric criteria alone are heterogeneous and can be classified by phenotype. Eosinophilic inflammation, a history of allergic disease, and smoke exposure are important components in the classification of ACOS. Each phenotype has a different underlying pathophysiology, set of characteristics, and prognosis. Medical treatment for ACOS should be tailored according to phenotype. A narrower definition of ACOS that includes both spirometric and clinical criteria is needed. PMID- 26161011 TI - Prevalence of and risk factors for endogenous endophthalmitis in patients with pyogenic liver abscesses. AB - BACKGROUND/AIMS: Although pyogenic liver abscesses (PLAs) can be successfully treated, the visual prognosis of patients with endogenous endophthalmitis (EE) associated with a PLA is poor. Early diagnosis and prompt intervention may salvage useful vision. Therefore, we investigated risk factors for EE in patients with PLA, to facilitate early diagnosis. METHODS: Data from 626 patients diagnosed with PLA between January 2004 and July 2013 were analyzed retrospectively. Patients were divided into two groups: those with liver abscess associated endogenous endophthalmitis (LAEE) and non-LAEE. RESULTS: The prevalence of EE in PLA patients was 1.92%. The mean age for all patients (373 males, 59.6%) was 62.8 years. Upon multivariate logistic regression, a liver abscess or another systemic infection (odds ratio [OR], 5.52; p = 0.005), an abscess in the right superior segment (OR, 5.26; p = 0.035), and Klebsiella pneumoniae infection (OR, 3.68; p = 0.039), were risk factors for LAEE. The final visual outcomes of patients with LAEE included no light perception in seven, hand motion only in three, and decreased visual acuity in two. Vitrectomy and early intravitreal injections of antibiotics improved visual acuity and preserved useful vision. CONCLUSIONS: PLA patients with other systemic infections, abscesses in the right superior segment, and K. pneumoniae infection require close monitoring and early intervention to treat LAEE. Intravitreal antibiotic injections or early vitrectomy may salvage useful vision. PMID- 26161012 TI - Prognostic value of hyponatremia in heart failure patients: an analysis of the Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (COAST) study. AB - BACKGROUND/AIMS: Hyponatremia is a well-known risk factor for poor outcomes in Western studies of heart failure (HF) patients. We evaluated the predictive value of hyponatremia in hospitalized Asian HF patients. METHODS: The Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) study enrolled hospitalized patients with systolic HF (ejection fraction < 45%) at eight centers in South Korea, Taiwan, and China. The relationship between admission sodium level and clinical outcomes was analyzed in 1,470 patients. RESULTS: The mean admission sodium level was 138 +/- 4.7 mmol/L, and 247 patients (16.8%) had hyponatremia defined as Na(+) < 135 mmol/L. The 12-month mortality was higher in hyponatremic patients (27.9% vs. 14.6%, p < 0.001), and hyponatremia was an independent predictor of 12-month mortality (hazard ratio, 1.72; 95% confidence interval, 1.12 to 2.65). During hospital admission, 57% of hyponatremic patients showed improvement without improvement in their clinical outcomes (p = 0.620). The proportion of patients with optimal medical treatment was only 26.5% and 44.2% at admission and discharge, respectively, defined as the combined use of angiotensin converting-enzyme inhibitor/angiotensin receptor blocker and beta-blocker. Underuse of optimal medical treatment was more pronounced in hyponatremic patients. CONCLUSIONS: In hospitalized Asian HF patients, hyponatremia at admission is common and is an independent predictor of poor clinical outcome. Furthermore, hyponatremic patients receive less optimal medical treatment than their counterparts. PMID- 26161014 TI - Clinical outcomes of extracorporeal membrane oxygenation support in patients with hematologic malignancies. AB - BACKGROUND/AIMS: The clinical outcomes of patients with hematologic malignancies who were treated with extracorporeal membrane oxygenation (ECMO) after the failu re of optimal conventional therapy were determined. METHODS: The medical records of all patients administered ECMO during their stay in a medical intensive care unit of Seoul St. Mary's Hospital between February 2010 and July 2013 were reviewed retrospectively. RESULTS: In total, 15 patients with hematologic malignancies were compared to 33 immunocompetent patients with documented cardiorespiratory failure. Underlying hematologic malignancies were significantly associated with lower overall survival (0.0% vs. 24.2%, p = 0.044). Mortality was significantly associated with a higher 24 hours ECMO inspired fraction of oxygen (0.71 +/- 0.24 vs. 0.47 +/- 0.13, p = 0.015), the development of infection after ECMO (87.5% vs. 25.0%, p = 0.001), and the presence of hyperbilirubinemia (70.0% vs. 0.0%, p < 0.001). Matching of the patients based on their Acute Physiology and Chronic Health Evaluation II scores confirmed the greater risk of mortality in patients with hematologic malignancies (survival: 0.0% vs. 40.0%, p = 0.017). The mean difference in inotropic-equivalent scores after ECMO was significantly lower in the immunocompetent patients than in those with hematologic malignancies (-59.22 +/- 97.83 vs. 53.87 +/- 164.46, p = 0.026). CONCLUSIONS: Patients with hematologic malignancies who require ECMO for respiratory support have poor outcomes. The incidence of complications in these patients did not significantly differ from that in immunocompetent patients. PMID- 26161013 TI - A combination of early warning score and lactate to predict intensive care unit transfer of inpatients with severe sepsis/septic shock. AB - BACKGROUND/AIMS: The modified early warning score (MEWS) is used to predict patient intensive care unit (ICU) admission and mortality. Lactate (LA) in the blood lactate (BLA) is measured to evaluate disease severity and treatment efficacy in patients with severe sepsis/septic shock. The usefulness of a combination of MEWS and BLA to predict ICU transfer in severe sepsis/septic shock patients is unclear. We evaluated whether use of a combination of MEWS and BLA enhances prediction of ICU transfer and mortality in hospitalized patients with severe sepsis/septic shock. METHODS: Patients with severe sepsis/septic shock who were screened or contacted by a medical emergency team between January 2012 and August 2012 were enrolled at a university-affiliated hospital with ~2,700 beds, including 28 medical ICU beds. RESULTS: One hundred patients were enrolled and the rate of ICU admittance was 38%. MEWS (7.37 vs. 4.85) and BLA concentration (5 mmol/L vs. 2.19 mmol/L) were significantly higher in patients transferred to ICU than those in patients treated in general wards. The combination of MEWS and BLA was more accurate than MEWS alone in terms of ICU transfer (C-statistics: 0.898 vs. 0.816, p = 0.019). The 28-day mortality rate was 19%. MEWS was the only factor significantly associated with 28-day mortality rate (odds ratio, 1.462; 95% confidence interval, 1.122 to 1.905; p = 0.005). CONCLUSIONS: The combination of MEWS and BLA may enhance prediction of ICU transfer in patients with severe sepsis/septic shock. PMID- 26161015 TI - Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury. AB - BACKGROUND/AIMS: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. METHODS: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. RESULTS: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 +/- 18.5 years and the mean peak creatinine level was 8.2 +/- 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. CONCLUSIONS: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome. PMID- 26161016 TI - Clinical features and outcomes of systemic amyloidosis with gastrointestinal involvement: a single-center experience. AB - BACKGROUND/AIMS: The gastrointestinal (GI) tract often becomes involved in patients with systemic amyloidosis. As few GI amyloidosis data have been reported, we describe the clinical features and outcomes of patients with pathologically proven GI amyloidosis. METHODS: We identified 155 patients diagnosed with systemic amyloidosis between April 1995 and April 2013. Twenty four patients (15.5%) were diagnosed with GI amyloidosis using associated symptoms, and the diagnoses were confirmed by direct biopsy. RESULTS: Among the 24 patients, 20 (83.3%) had amyloidosis light chain (AL), three (12.5%) had amyloid A, and one (4.2%) had transthyretin-related type amyloidosis. Their median age was 57 years (range, 37 to 72), and 10 patients were female (41.7%). The most common symptoms of GI amyloidosis were diarrhea (11 patients, 45.8%), followed by anorexia (nine patients, 37.5%), weight loss, and nausea and/or vomiting (seven patients, 29.2%). The histologically confirmed GI tract site in AL amyloidosis was the stomach in 11 patients (55.0%), the colon in nine (45.0%), the rectum in seven (35.0%), and the small bowel in one (5.0%). Patients with GI involvement had a greater frequency of organ involvement (p = 0.014). Median overall survival (OS) in patients with GI involvement was shorter (7.95 months; range, 0.3 to 40.54) than in those without GI involvement (15.84 months; range, 0.0 to 114.53; p = 0.069) in a univariate analysis. A multivariate analysis of prognostic factors for AL amyloidosis revealed that GI involvement was not a significant predictor of OS (p = 0.447). CONCLUSIONS: The prognosis of patients with AL amyloidosis and GI involvement was poorer than those without GI involvement, and they presented with more organ involvement and more advanced disease than those without organ involvement. PMID- 26161017 TI - Infections after lung transplantation: time of occurrence, sites, and microbiologic etiologies. AB - BACKGROUND/AIMS: Infections are major causes of both early and late death after lung transplantation (LT). The development of prophylaxis strategies has altered the epidemiology of post-LT infections; however, recent epidemiological data are limited. We evaluated infections after LT at our institution by time of occurrence, site of infections, and microbiologic etiologies. METHODS: All consecutive patients undergoing lung or heart-lung transplantation between October 2008 and August 2014 at our institution were enrolled. Cases of infections after LT were initially identified from the prospective registry database, which was followed by a detailed review of the patients' medical records. RESULTS: A total of 108 episodes of post-LT infections (56 bacterial, 43 viral, and nine fungal infections) were observed in 34 LT recipients. Within 1 month after LT, the most common bacterial infections were catheter-related bloodstream infections (42%). Pneumonia was the most common site of bacterial infection in the 2- to 6-month period (28%) and after 6 months (47%). Cytomegalovirus was the most common viral infection within 1 month (75%) and in the 2- to 6-month period (80%). Respiratory viruses were the most common viruses after 6 months (48%). Catheter-related candidemia was the most common fungal infection. Invasive pulmonary aspergillosis developed after 6 months. Survival rates at the first and third years were 79% and 73%, respectively. CONCLUSIONS: Although this study was performed in a single center, we provide valuable and recent detailed epidemiology data for post-LT infections. A further multicenter study is required to properly evaluate the epidemiology of post-LT infections in Korea. PMID- 26161018 TI - Drug utilization review of mupirocin ointment in a Korean university-affiliated hospital. AB - BACKGROUND/AIMS: Intranasal mupirocin and chlorhexidine bathing are candidate strategies to prevent healthcare-associated infections caused by methicillin resistant Staphylococcus aureus (MRSA). In Korea, intranasal mupirocin is not available, and mupirocin ointment, an over-the-counter drug, has been used indiscriminately. Furthermore, because it is covered by health insurance, mupirocin is easy to prescribe within hospitals. METHODS: We performed a mupirocin drug utilization review (DUR) within Hallym University Sacred Heart Hospital. Annual use of mupirocin was investigated between 2003 and 2013, and monthly consumption of mupirocin was assessed during the final 2-year period. The DUR focused on August 2012, the period of highest use of mupirocin. Also, we investigated trends in mupirocin resistance in MRSA between 2011 and 2013. RESULTS: Annual consumption of mupirocin increased from 3,529 tubes in 2003 to 6,475 tubes in 2013. During August 2012, 817 tubes were prescribed to 598 patients; of these, 84.9% were prescribed to outpatients, and 77.6% at the dermatology department. The most common indication was prevention of skin infections (84.9%), and the ointment was combined with systemic antibiotics in 62.9% of cases. The average duration of systemic antibiotic administration was about 7.8 days. The rate of low-level mupirocin resistance in MRSA increased from 8.0% to 22.0%, and that of high-level mupirocin resistance increased from about 4.0% to about 7.5%. CONCLUSIONS: Inappropriate use of mupirocin is prevalent. Considering the increase in resistance and the future application of intranasal mupirocin, prophylactic use of mupirocin in dermatology departments should be reconsidered. PMID- 26161019 TI - Allopurinol hypersensitivity syndrome in patients with hematological malignancies: characteristics and clinical outcomes. AB - BACKGROUND/AIMS: Allopurinol is a urate-lowering agent that is commonly used to prevent chemotherapy-related hyperuricemia. Allopurinol hypersensitivity syndrome (AHS) is a disorder involving multiple organs, which may be accompanied by cutaneous adverse reactions. We identified the characteristics and clinical outcomes of chemotherapy-associated AHS in patients with hematological malignancies. METHODS: This retrospective single-center study included 26 AHS patients (11 with and 15 without hematological malignancies) admitted to Seoul St. Mary's Hospital. AHS was defined using the criteria of Singer and Wallace. Comparisons were made using the Mann-Whitney U test and Fisher exact test as appropriate. RESULTS: In patients with a hematological malignancy and AHS, statistically significant differences were observed in terms of younger age at onset; shorter duration of exposure; higher starting and maintenance doses of allopurinol; lower incidence of eosinophilia, leukocytosis, and underlying renal insufficiency; and more frequent occurrence of fever compared to AHS patients without a hematological malignancy. Two AHS patients with a hematological malignancy were examined for human leukocyte antigen (HLA)-B typing, but neither patient harbored the HLA-B*5801 allele. All of the patients ceased allopurinol treatment, with most patients making a full recovery. Two patients in the study died; however, these deaths were unrelated to AHS. One patient developed serious sequelae of AHS that required hemodialysis. CONCLUSIONS: Physicians who prescribe allopurinol for the prevention of chemotherapy-related hyperuricemia should be aware of the unique risk of AHS, even in patients with hematological malignancies who do not have known risk factors for AHS. Novel urate-lowering agents should be considered alternative treatments. PMID- 26161020 TI - Quantitative analysis of nailfold capillary morphology in patients with fibromyalgia. AB - BACKGROUND/AIMS: Nailfold capillaroscopy (NFC) has been used to examine morphological and functional microcirculation changes in connective tissue diseases. It has been demonstrated that NFC patterns reflect abnormal microvascular dynamics, which may play a role in fibromyalgia (FM) syndrome. The aim of this study was to determine NFC patterns in FM, and their association with clinical features of FM. METHODS: A total of 67 patients with FM, and 30 age- and sex-matched healthy controls, were included. Nailfold capillary patterns were quantitatively analyzed using computerized NFC. The parameters of interest were as follows: number of capillaries within the central 3 mm, deletion score, apical limb width, capillary width, and capillary dimension. Capillary dimension was determined by calculating the number of capillaries using the Adobe Photoshop version 7.0. RESULTS: FM patients had a lower number of capillaries and higher deletion scores on NFC compared to healthy controls (17.3 +/- 1.7 vs. 21.8 +/- 2.9, p < 0.05; 2.2 +/- 0.9 vs. 0.7 +/- 0.6, p < 0.05, respectively). Both apical limb width (um) and capillary width (um) were significantly decreased in FM patients (1.1 +/- 0.2 vs. 3.7 +/- 0.6; 5.4 +/- 0.5 vs. 7.5 +/- 1.4, respectively), indicating that FM patients have abnormally decreased digital capillary diameter and density. Interestingly, there was no difference in capillary dimension between the two groups, suggesting that the length or tortuosity of capillaries in FM patients is increased to compensate for diminished microcirculation. CONCLUSIONS: FM patients had altered capillary density and diameter in the digits. Diminished microcirculation on NFC may alter capillary density and increase tortuosity. PMID- 26161021 TI - Extramedullary relapse of multiple myeloma presenting as massive upper gastrointestinal bleeding: a rare complication. PMID- 26161022 TI - Type 2 myocardial infarction after ingestion of mad honey in a patient with normal coronary arteries. PMID- 26161023 TI - Fatal ischemic stroke in a case of progressive moyamoya vasculopathy associated with uncontrolled thyrotoxicosis. PMID- 26161024 TI - Metastatic sarcomatoid carcinoma presenting as a pedunculated mass on the floor of the mouth. PMID- 26161025 TI - Imatinib mesylate-induced interstitial lung disease in a patient with prior history of Mycobacterium tuberculosis infection. PMID- 26161026 TI - Hepatic hydatid cyst. PMID- 26161027 TI - Importance of careful Tc-MIBI interpretation in patients with thyroid cancer and primary hyperparathyroidism. PMID- 26161028 TI - DC-SIGN (CD209) Carbohydrate Recognition Domain Is Not Polymorphic in Dengue Virus-Infected Indonesian Patients. AB - Dengue virus (DENV) infection is a significant burden in Indonesia and other tropical countries. DENV infection has a wide spectrum of clinical manifestations, i.e. asymptomatic, dengue fever, dengue hemorrhagic fever and dengue shock syndrome. The variety of clinical manifestations may be due to the diversity of genetic constitution of the host. The C-type lectin DC-SIGN (CD209) has been identified as the major dengue receptor on human dendritic cells. There are at least five polymorphisms in exon 5 and 6 of the DC-SIGN encoded gene which have been identified and recorded in dbSNP. The aim of this work is to measure the frequency of these polymorphisms among asymptomatic and hospitalized DENV infected patients. We enrolled 23 hospitalized and 73 asymptomatic DENV-infected patients. Among the subjects, we performed PCR amplification and DNA direct seqencing for 23 hospitalized DENV-infected patients and 24 asymptomatic DENV infected patients. The result showed that there were no polymorphic nucleotides in the CD209 encoded gene among the patients. PMID- 26161029 TI - Understanding of Essential Elements Required in Informed Consent Form among Researchers and Institutional Review Board Members. AB - The process of informed consent remains a constant challenge in clinical research. The aim of the present study was to evaluate the understanding of researchers and members of Institutional Review Boards (IRBs) regarding the essential elements of an Informed Consent Form (ICF) as required by internationally recognized regulations. Using eight case studies to illustrate basic ethical elements, the study involved 107 participants, mainly from the Asia Pacific and African regions. The results showed that most of the participants had general knowledge regarding the essential elements required in an ICF. However, the issues of confidentiality of data and payment for study participation proved to be problematic for some participants, accounting for 35% and 28% of all incorrect answers respectively. This suggests that participants' understanding of the underlying concepts of the required ICF elements is limited. Ethical training of researchers and IRB members, particularly in the Asia Pacific and African regions, concerning valid informed consent is still needed. PMID- 26161030 TI - Understanding Postpartum Healthcare Services and Exploring the Challenges and Motivations of Maternal Health Service Providers in the Philippines: a Qualitative Study. AB - BACKGROUND: Given the shortage of medical professionals in the Philippines, Barangay Health Workers (BHWs) may play a role in providing postpartum healthcare services. However, as there are no reports regarding BHW activities in postpartum healthcare, we conducted this study to understand postpartum healthcare services and to explore the challenges and motivations of maternal health service providers. METHODS: Focus group interview (FGI) of 13 participants was conducted as qualitative research methodology at Muntinlupa City. The results were analyzed according to the interview guide. The proceedings of the FGI were transcribed verbatim, and researchers read and coded the transcripts. The codes were then used to construct categories. RESULTS: Four important activities were highlighted among 11 analysis codes. These activities were "Assessment of postpartum women's conditions," "Recommendation to visit a health facility," "Measurement of blood pressure and vitamin intake," and "Providing postpartum health information." Among five analysis codes, we identified three challenges that BHWs face, which were "No current information regarding postpartum care," "Some postpartum women do not want to receive healthcare services from BHW," and "Too many assigned postpartum women." Among five analysis codes, we identified two reasons for continuing BHW activities, which were "Hospitality to help postpartum women and their family in the community" and "Performance of mission in providing BHW services." CONCLUSION: This study is the first to evaluate BHW activities in postpartum healthcare services. Our results indicate that BHWs play a potentially important role in evaluating postpartum women's physical and mental conditions through home-visiting services. However, several difficulties adversely affected their activities, and these must be addressed to maximize the contributions of BHWs to the postpartum healthcare system. PMID- 26161031 TI - Unnecessary Dieting Intention and Behavior among Female Students in Naha City, Japan. AB - Weight concerns and dieting are prevalent among female adolescents both in Western and Asian countries. They can result in negative psychological and physiological consequences. This study aimed to examine the relative importance of social and personal factors in the decision to diet among female adolescent students in Japan, applying the Theory of Planned Behavior. Data were collected from five junior high schools and three high schools in Naha City, Okinawa Prefecture, in 2010, through self-administered questionnaires. The data of 756 female students were assessed. The independent variables included social factor variables (norms) and personal factor variables (attitude to dieting, perceived behavior control, body esteem, body-figure discrepancy and past dieting). The dependent variables were dieting intention and behavior. Hierarchical multiple regression analyses were performed to examine three models: model 1 (age and obesity index), model 2 (social factor variables with age and obesity index) and model 3 (all variables). Although model 2 failed to explain a substantial proportion of the variance, model 3 explained approximately a half of the variance for intention (R(2) = 0.507) and more than one third of the variance for behavior (R(2) = 0.376). Past experience of dieting was the best predictor of both dieting intention and behavior. Body esteem was the second best predictor for dieting behavior. In conclusion, personal factors are more likely than social factors to drive the dieting decision. Diet education programs should consider targeting frequent dieters and those with poor body esteem. PMID- 26161033 TI - Loiasis in a Japanese Traveler Returning from Central Africa. AB - We encountered a probable case of loiasis in a returned traveler from Central Africa. A 52-year-old Japanese woman presented to our hospital complaining of discomfort in her eyes and skin. She reported having frequently visited Central Africa over many years and having been extensively exposed to the rainforest climate and ecosystem. Although no microfilariae were found in her blood, there was an elevated level of IgG antibodies against the crude antigens of Brugia pahangi, which have cross-reactivity with Loa loa. She was treated with albendazole for 21 days, after which the antigen-specific IgG level decreased and no relapse occurred. PMID- 26161032 TI - Social Sciences for the Prevention of Blindness. AB - Organizations working for the elimination of Chlamydia-triggered blindness (trachoma) follow the WHO SAFE strategy (surgery for trichiasis, antibiotics, face washing and environmental changes) with the aim to achieve a minimum of 80% of children with clean faces in endemic communities, mass treatment covering the whole district with trachoma rates of 10% or more and surveillance plans. Trachoma recurrence that is common after implementing the SAFE strategy 3, 5 or even 7 times evidence that the cognitive processes requiring assimilation and integration of knowledge did not register with parents, caretakers and children. Moreover, repeated awareness campaigns to improve hygiene did not systematically produce irreversible changes of behavior in neglected populations. In view of this evidence, the rational behind mass drug administration as the mainstay of preventable blindness elimination demands a wider scope than simple mathematical models. The reluctance to see disappointing outcomes that leads to repeated interventions may suggest from a sociologic point of view that the strategies are products of those evaluating the activities of those who fund them and vice versa. A similar articulation emerges for reciprocal interactions between researchers and those judging the pertinence and quality of their work. So far, the lack of autocritic elimination strategy approaches may expose inbred circles that did not properly grasp the fact that antibiotics, trichiasis surgery and education limited to improvement of hygiene are inefficient if not associated with long-term basic educational actions in schools. PMID- 26161034 TI - Calixarene-Mediated Liquid-Membrane Transport of Choline Conjugates. AB - A series of supramolecular calixarenes efficiently transport distinct molecular species through a liquid membrane when attached to a receptor-complementary choline handle. Calix-[6]arene hexacarboxylic acid was highly effective at transporting different target molecules against a pH gradient. Both carboxylic- and phosphonic-acid-functionalized calix[4]arenes effect transport without requiring a pH or ion gradient. NMR binding studies, two-phase solvent extraction, and three-phase transport experiments reveal the necessary and subtle parameters to effect the transport of molecules attached to a choline "handle". On the other hand, rescorin[4]arene cavitands, which have similar guest recognition profiles, did not transport guest molecules. These developments reveal new approaches towards attempting synthetic-receptor-mediated selective small-molecule transport in vesicular and cellular systems. PMID- 26161035 TI - Calixarene-Mediated Liquid Membrane Transport of Choline Conjugates 2: Transport of Drug-Choline Conjugates and Neurotransmitters. AB - Lower rim carboxylic acid calix[n]arenes and upper rim phosphonic acid functionalized calix[4]arenes effect selective transport of distinct molecular payloads through a liquid membrane. The secret to this success lies in the attachment of a receptor-complementary handle. We find that the trimethylammonium ethylene group present in choline is a general handle for the transport of drug and drug-like species. Furthermore, neurotransmitters possessing ionizable amine termini are also transported. Some limitations to this strategy have been uncovered as payloads become increasingly lipophilic. These developments reveal new approaches to synthetic receptor-mediated selective small molecule transport in vesicular and cellular systems. PMID- 26161036 TI - A Geography of Unmarried Cohabitation in the Americas. AB - BACKGROUND: In the context of increasing cohabitation and growing demand for understanding the driving forces behind the cohabitation boom, most analyses have been carried out at a national level, not accounting for regional heterogeneity within countries. OBJECTIVE: This paper presents the geography of unmarried cohabitation in the Americas. We offer a large-scale, cross-national perspective together with small-area estimates of cohabitation. We decided to produce this map because: (i) geography unveils spatial heterogeneity and challenges explanatory frameworks that may work at the international level but have low explanatory power in regard to intra-national variation. (ii) we argue that historical pockets of cohabitation can still be identified by examining the current geography of cohabitation. (iii) our map is a first step toward understanding whether the recent increase in cohabitation is an intensification of pre-existing traditions or whether it has different roots that also imply a new geography. METHODS: Census microdata from 39 countries and 19,000 local units have been pulled together to map the prevalence of cohabitation among women. RESULTS: The results show inter- and intra-national regional contrasts. The highest rates of cohabitation are found in areas of Central America, the Caribbean, Colombia and Peru. The lowest rates are mainly found in the United States and Mexico. In all countries the spatial autocorrelation statistics indicates substantial spatial heterogeneity. CONCLUSIONS: Our results raise the question as to which forces have shaped these patterns and remind us that such forces need to be taken into account to understand recent patterns, particularly increases, in cohabitation. PMID- 26161038 TI - Tumor necrosis factor alpha inhibits ovulation and induces granulosa cell death in rat ovaries. AB - PURPOSE: We evaluated the role of tumor necrosis factor alpha (TNFalpha) in rat ovulation and granulosa cell death of ovarian follicles during the periovulatory stage. METHODS: Immature rats primed with pregnant mare serum gonadotropin were injected intraperitoneally with human chorionic gonadotropin (hCG), and TNFalpha was injected into the bursa 48 h later. The total number of released oocytes was counted. Apoptosis was measured with terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and the expression of cleaved caspase 3 and Bax/Bcl-2. Autophagy was assessed by the expression of light chain protein 3 (LC3) and autophagosomes under transmission electron microscopy. RESULTS: TNFalpha significantly decreased the number of released oocytes, and many unruptured follicles were observed. TUNEL analysis revealed a larger number of apoptotic cells, and the cleaved caspase 3 and Bax/Bcl-2 increased more than that of the control 12 h after hCG administration. Furthermore, the expression of LC3 wwas significantly higher than that of the control, and autophagosomes were observed in the cytoplasm. CONCLUSIONS: Our data indicated that TNFalpha is an important mediator of ovulation in terms of decreasing the number of released oocytes and inducing granulosa cell death of unruptured follicles via apoptosis and autophagy for remodeling ovarian tissues. PMID- 26161039 TI - A retrospective analysis of breast cancer subtype based on ER/PR and HER2 status in Ghanaian patients at the Korle Bu Teaching Hospital, Ghana. AB - BACKGROUND: Breast cancer is a heterogeneous disease composed of multiple subgroups with different molecular alterations, cellular composition, clinical behaviour, and response to treatment. This study evaluates the occurrence of the various subtypes and their clinical and pathological behaviour in the Ghanaian breast cancer population at the Korle Bu Teaching Hospital (KBTH). METHODS: Retrospective review of case notes of patients who had completed treatment for breast cancer at the KBTH within the last 5 years was conducted between April 2011 and March 2012. Subtypes were determined by immunohistochemistry classification based on expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). RESULT: A total of 165 cases contributed to this study. The mean age at diagnosis was 52.5 +/- 12.1 years. Tumour size ranged from 0.8 cm to 15 cm with a mean of 4.9 +/- 2.8 cm and median of 4 cm. Tumour grade was Grade I 8.3 %, Grade II 60.8 % and Grade III 30.8 %. ER, PR and HER2/neu receptor positivity was 32.1, 25.6 and 25.5 % respectively. Almost half (49.4 %) of the study population had triple negative tumours. Luminal A, luminal B and non-luminal HER2 were 25.6, 12.2, and 12.8 % respectively. No statistically significant association was seen between subtype and tumour size, tumour grade, lymph node status and age at diagnosis. CONCLUSION: Triple negative tumour is the most occurring subtype in the Ghanaian breast cancer population treated at the Korle Bu Teaching Hospital. Lack of association seen between subtypes and their clinical and pathological behaviour could be due to small sample size. PMID- 26161037 TI - How are pluripotent cells captured in culture? AB - In mice, three pluripotent stem cell lines have been established from different stage of developing embryo, which are embryonic stem (ES) cell, post-implantation epiblast stem cell (EpiSC), and embryonic germ (EG) cell. ES cell and EG cell share many common features including factor requirement, colony morphology, and gene expression pattern. On the other hand, EpiSC needs different external signal inputs, exhibits flattened colony morphology, and a different set of gene expression patterns. In addition, the germ line competency of EpiSCs is still unclear. To distinguish the differences between them, they are defined by the words "naive" and "primed" pluripotent cells, respectively. This article introduces how pluripotent stem cell lines are established in culture, and how much those cells in vitro are similar or relevant to their in vivo origin and the knowledge about transcription factors to support this state. PMID- 26161040 TI - Increased expression of Six1 correlates with progression and prognosis of prostate cancer. AB - Sineoculis homeobox homolog 1 (Six1), normally a developmentally restricted transcriptional regulator, is frequently dysregulated in mutiple cancers. Increasing evidences show that overexpression of Six1 plays a key role in tumorigenesis. However, the Six1 expression status and its relationship with the clinicopathological characteristics in prostate cancer were unclear. In this study, the mRNA and protein levels of Six1 in prostate cancer tissues and normal prostate tissues were evaluated. The clinicopathological significance of Six1 was investigated by immunohistochemistry (IHC) on a prostate cancer tissue microarray. The cut-off score for high expression of Six1 was determined by the receiver-operating characteristic (ROC) analysis. The correlation between Six1 protein expression and clinicopathological characteristics of prostate cancer was analyzed by Chi-square test. Increased expression of Six1 protein was observed in the majority of prostate cancer, compared with their paired adjacent normal prostate tissues. When Six1 high expression percentage was determined to be above 55 % (area under ROC curve = 0.881, P = 0.000), high expression of Six1 was observed in 55.6 % (80/144) of prostate cancer tissues and low expression of Six1 was observed in all normal prostate tissues by IHC. Increased expression of Six1 in patients was correlated with high histological grade (chi2 = 58.651, P = 0.00), advanced clinical stage (chi2 = 57.330, P = 0.000), high Gleason score (chi2 = 63.480, P = 0.000), high primary tumor grade (chi2 = 57.330, P = 0.000) and positive regional lymph node metastasis (chi2 = 19.294, P = 0.000). Furthermore, univariate and multivariate survival analysis suggested that Six1 was an independent prognostic indicator for overall survival (P < 0.05). This study suggests that Six1 could be served as an additional biomarker in identifying prostate cancer patients at risk of tumor progression, might potentially be used for predicting survival outcome of patients with prostate cancer. PMID- 26161041 TI - AXIN2 rs2240308 polymorphism contributes to increased cancer risk: evidence based on a meta-analysis. AB - BACKGROUND: Variants in the axis inhibition 2 (AXIN2) gene might alter the protein's structure or function or create a multiprotein destruction complex in the Wnt signaling pathway and thus affect an individual's susceptibility to cancer. The objective of this study is to evaluate broadly the evidence available for the AXIN2 rs2240308 polymorphism and risk of cancer. METHODS: A comprehensive literature search was undertaken for eligible studies in Embase, PubMed, and Cochrane Library up to Nov 30, 2014. Odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were used to measure the strength of the models. RESULTS: Eight articles (10 case-control studies with 1,502 cases and 1,590 controls) were included in this analysis. Overall, the AXIN2 rs2240308 polymorphism was associated with a significant increase in the risk of cancer (G allele vs. A allele: OR = 1.21, 95 % CI = 1.05-1.40, I (2) = 39.5 % and P Q = 0.094 for heterogeneity; GG vs. AA: OR = 1.30, 95 % CI = 1.04-1.63, I (2) = 35.9 % and P Q = 0.121 for heterogeneity; GG vs. GA + AA: OR = 1.36, 95 % CI = 1.17 1.58, I (2) = 19.5 % and P Q = 0.263 for heterogeneity). Asian populations showed similar results. Stratified analysis by cancer types indicated that the AXIN2 rs2240308 polymorphism increases the risk of lung cancer (G allele vs. A allele: OR = 1.36, 95 % CI = 1.17-1.59; GA vs. AA: OR = 1.43, 95 % CI = 1.01 2.02; GG vs. AA: OR = 1.93, 95 % CI = 1.36-2.75; GG + GA vs. AA: OR = 1.65, 95 % CI = 1.18-2.30; GG vs. GA + AA: OR = 1.45, 95 % CI = 1.18-1.79. All I (2) < 50 % and P Q > 0.100 for heterogeneity). CONCLUSIONS: This study showed that the AXIN2 rs2240308 polymorphism contribute to increasing the risk of cancer, especially lung cancer in Asian populations. PMID- 26161042 TI - Propensity score weighting for addressing under-reporting in mortality surveillance: a proof-of-concept study using the nationally representative mortality data in China. AB - BACKGROUND: National mortality data are obtained routinely by the Disease Surveillance Points system (DSPs) in China and under-reporting is a big challenge in mortality surveillance. METHODS: We carried out an under-reporting field survey in all 161 DSP sites to collect death cases during 2009-2011, using a multi-stage stratified sampling. To identify under-reporting, death data were matched between field survey system and the routine online surveillance system by an automatic computer checking followed by a thorough manual verification. We used a propensity score (PS) weighting method based on a logistic regression to calculate the under-reporting rate in different groups classified by age, gender, urban/rural residency, geographic locations and other mortality related variables. For comparison purposes, we also calculated the under-reporting rate by using capture-mark-recapture (CMR) method. RESULTS: There were no significant differences between the field survey system and routine online surveillance system in terms of age group, causes of death, highest level of diagnosis and diagnostic basis. The overall under-reporting rate in the DSPs was 12.9 % (95%CI 11.2 %, 14.6 %) based on PS. The under-reporting rate was higher in the west (18.8 %, 95%CI 16.5 %, 21.0 %) than the east (10.1 %, 95%CI 8.6 %, 11.3 %) and central regions (11.2 %, 95%CI 9.6 %, 12.7 %). Among all age groups, the under reporting rate was highest in the 0-5 year group (23.7 %, 95%CI 16.1 %, 35.5 %) and lowest in the 65 years and above group (12.4 %, 95%CI 10.9 %, 13.6 %). The under-reporting rates in each group by PS were similar to the results calculated by the CMR methods. CONCLUSIONS: The mortality data from the DSP system in China needs to be adjusted. Compared to the commonly used CMR method in the estimation of under-reporting rate, the results of propensity score weighting method are similar but more flexible when calculating the under-reporting rates in different groups. Propensity score weighting is suitable to adjust DSP data and can be used to address under-reporting in mortality surveillance in China. PMID- 26161043 TI - Return Migration as Failure or Success?: The Determinants of Return Migration Intentions Among Moroccan Migrants in Europe. AB - Different migration theories generate competing hypotheses with regard to determinants of return migration. While neoclassical migration theory associates migration to the failure to integrate at the destination, the new economics of labour migration sees return migration as the logical stage after migrants have earned sufficient assets and knowledge and to invest in their origin countries. The projected return is then likely to be postponed for sustained or indefinite periods if integration is unsuccessful. So, from an indication or result of integration failure return is rather seen as a measure of success. Drawing on recent survey data (N = 2,832), this article tests these hypotheses by examining the main determinants of return intention among Moroccan migrants across Europe. The results indicate that structural integration through labour market participation, education and the maintenance of economic and social ties with receiving countries do not significantly affect return intentions. At the same time, investments and social ties to Morocco are positively related, and socio cultural integration in receiving countries is negatively related to return migration intentions. The mixed results corroborate the idea that there is no uniform process of (return) migration and that competing theories might therefore be partly complementary. PMID- 26161044 TI - Infant Preference for Natural Texture Statistics is Modulated by Contrast Polarity. AB - Adult observers are sensitive to statistical regularities present in natural images. Developmentally, research has shown that children do not show sensitivity to these natural regularities until approximately 8-10 years of age. This finding is surprising given that even infants gradually encode a range of high-level statistical regularities of their visual environment in the first year of life, We suggest that infants may in fact exhibit sensitivity to natural image statistics under circumstances where images of complex, natural textures, such as a photograph of rocks, are used as experimental stimuli and natural appearance is substantially manipulated. We tested this hypothesis by examining how infants' visual preference for real versus computer-generated synthetic textures was modulated by contrast negation, which produces an image similar to a photographic negative. We observed that older infants' (9-months of age) preferential looking behavior in this task was affected by contrast polarity, suggesting that the infant visual system is sensitive to deviations from natural texture appearance, including (1) discrepancies in appearance that differentiate natural and synthetic textures from one another and (2) the disruption of contrast polarity following negation. We discuss our results in the context of adult texture processing and the "perceptual narrowing" of visual recognition during the first year of life. PMID- 26161045 TI - The NIH Office of Biotechnology Activities Site Visit Program: Observations About Institutional Oversight of Recombinant and Synthetic Nucleic Acid Molecule Research. AB - Institutions that receive National Institutes of Health (NIH) funding for research involving recombinant or synthetic nucleic acid molecules are required, as a term and condition of their funding, to comply with the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) (NIH, 2013). Under the NIH Guidelines, institutions must establish and register an Institutional Biosafety Committee (IBC) with the NIH. The IBC is then responsible for reviewing and approving research projects subject to the NIH Guidelines. The IBC review of projects involving recombinant or synthetic nucleic acid molecules is critical to ensuring that such research is conducted in a safe and responsible manner. In 2006, staff from NIH began conducting educational site visits to institutions that had an IBC registered with NIH. The purpose of these site visits is to assist IBCs with their institutional programs of oversight for recombinant or synthetic nucleic molecules. Based on our findings, the site visit program has been beneficial to institutional biosafety programs. The information gathered during the site visits has allowed NIH to tailor its educational materials to help institutions address their oversight challenges. Additionally, since NIH's visits are primarily educational in nature, we have been able to foster a positive environment in which IBC members and staff feel comfortable reaching out to NIH for advice and assistance. PMID- 26161046 TI - Do Modifiable Cardiovascular Risk Factors Differ By Rural Classification in Women Who Enroll in a Weight Loss Intervention? AB - PURPOSE: If clinicians and researchers are aware of specific cardiovascular risks associated with women's rural status, whether it be large or small/isolated rural areas, it may help in developing more relevant rural resources. The purpose of this study was to examine whether there were differences in modifiable cardiovascular risk factors of overweight and obese rural women living in large or small/isolated rural areas. SAMPLE: This secondary analysis examined baseline cross-sectional data from the "Web-based Weight Loss and Weight Maintenance Intervention for Older Rural Women" clinical trial. Analysis included data from 299 rural Midwestern women, ages 40-69 years with a baseline body mass index of 28-45 kg/m2, who provided rural classification data and were randomized into groups. METHODS: Demographic and biomarker baseline data were used. Chi-square and independent t-tests were used for data analyses. FINDINGS: There are no significant differences found in overweight and obese women with cardiovascular risk factors when compared to rural classification, with one exception. Total cholesterol was associated with rural classification (p=0.047), where women living in large rural areas were more likely to have elevated total cholesterol levels (>=240 mg/dL) compared to women living in small/isolated areas (18.5% vs. 10.0%, respectively). Demographic characteristics such as age and education demonstrated no significant differences by rural classification; however, the majority of women in this study were of high socioeconomic status. CONCLUSIONS: Although this secondary analysis found that rural women have similar cardiovascular risk factors and demographic characteristics, this study highlights the need for clinicians to carefully consider the rural community characteristics for primary prevention. PMID- 26161047 TI - Integration of Technology-based Behavioral Health Interventions in Substance Abuse and Addiction Services. AB - The past decade has witnessed revolutionary changes to the delivery of health services, ushered in to a great extent by the introduction of electronic health record systems. More recently, a new class of technological advancements technology-based behavioral health interventions, which involve the delivery of evidence-informed practices via computers, web-based applications, mobile phones, wearable sensors, or other technological platforms-has emerged and is primed to once again radically shift current models for behavioral healthcare. Despite the promise and potential of these new therapeutic approaches, a greater understanding of the impact of technology-based interventions on cornerstone issues of mental health and addiction services-namely access, quality, and cost is needed. The current review highlights 1) relevant conceptual frameworks that guide this area of research, 2) key studies that inform the relevance of technology-based interventions for behavioral healthcare access, quality, and cost, 3) pressing methodological issues that require attention, 4) unresolved questions that warrant further investigation, and 5) practical implications that underscore important new directions for this emerging area of research. PMID- 26161048 TI - Nanostructured gold dsDNA sensor for early detection of breast cancer by beta protein 1 (BP1). AB - Beta protein 1 (BP1) is a homeobox protein expressed in 80% of breast cancer cells in either estrogen receptor (ER) positive or ER negative breast cancer. However, it is barely detectable in normal breast tissues. In this project we present an electrochemical DNA nanostructured gold biosensor for detection of BP1. The gold sensor is first electrochemically nanostructured in 0.5 M sulfuric acid to reach superior conductivity, larger surface area, and higher stability. Nanostructured gold surface was characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The nanostructured gold sensor is then modified with double-stranded (ds) DNA mapping the genomic sequence that contains the binding site for BP1. A redox-active probe (methylene blue) was intercalated in dsDNA to monitor the binding event of BP1. A linear correlation of the electrochemical response by concentration of BP1 was obtained (R2 = 0.998) with a limit of detection of 1.2 nM. This nanostructured gold dsDNA sensor is shown to be sensitive, selective, stable, and reusable allowing for its potential clinical use. PMID- 26161050 TI - Rich club network analysis shows distinct patterns of disruption in frontotemporal dementia and Alzheimer's disease. AB - Diffusion imaging and brain connectivity analyses can reveal the underlying organizational patterns of the human brain, described as complex networks of densely interlinked regions. Here, we analyzed 1.5-Tesla whole-brain diffusion weighted images from 64 participants - 15 patients with behavioral variant frontotemporal (bvFTD) dementia, 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly controls. Based on whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We examined how bvFTD and EOAD disrupt the weighted 'rich club' - a network property where high-degree network nodes are more interconnected than expected by chance. bvFTD disrupts both the nodal and global organization of the network in both low- and high-degree regions of the brain. EOAD targets the global connectivity of the brain, mainly affecting the fiber density of high degree (highly connected) regions that form the rich club network. These rich club analyses suggest distinct patterns of disruptions among different forms of dementia. PMID- 26161049 TI - Complementary and alternative drug therapy versus science-oriented medicine. AB - This opinion deals critically with the so-called complementary and alternative medical (CAM) therapy on the basis of current data. From the authors' perspective, CAM prescriptions and most notably the extensive current endeavours to the "integration" of CAM into conventional patient care is problematic in several respects. Thus, several CAM measures are used, although no specific effects of medicines can be proved in clinical studies. It is extensively explained that the methods used in this regard are those of evidence-based medicine, which is one of the indispensable pillars of science-oriented medicine. This standard of proof of efficacy is fundamentally independent of the requirement of being able to explain efficacy of a therapy in a manner compatible with the insights of the natural sciences, which is also essential for medical progress. Numerous CAM treatments can however never conceivably satisfy this requirement; rather they are justified with pre-scientific or unscientific paradigms. The high attractiveness of CAM measures evidenced in patients and many doctors is based on a combination of positive expectations and experiences, among other things, which are at times unjustified, at times thoroughly justified, from a science-oriented view, but which are non-specific (context effects). With a view to the latter phenomenon, the authors consider the conscious use of CAM as unrevealed therapeutic placebos to be problematic. In addition, they advocate that academic medicine should again systematically endeavour to pay more attention to medical empathy and use context effects in the service of patients to the utmost. The subsequent opinion discusses the following after an introduction to medical history: the definition of CAM; the efficacy of most common CAM procedures; CAM utilisation and costs in Germany; characteristics of science-oriented medicine; awareness of placebo research; pro and contra arguments about the use of CAM, not least of all in terms of aspects related to medical ethics. PMID- 26161051 TI - Cytomegalovirus-associated ulceration of gastric conduit after chemoradiotherapy following esophagectomy for cancer. AB - A 64-year-old man underwent radical esophagectomy for cancer and simultaneous reconstruction using the gastric conduit through the posterior mediastinum. Two courses of adjuvant chemotherapy were performed. Twenty-eight months postoperatively, recurrence of the cancer was detected in the mediastinal lymph nodes, and he underwent concurrent chemoradiotherapy and boost chemotherapy. Endoscopy was then performed to investigate the cause of epigastralgia, and multiple ulcerations were found in the lesser curvature of the gastric conduit. Although a proton-pump inhibitor was orally administered, the ulceration was intractable. Re-examination of the original biopsy specimens and serological testing revealed positivity for cytomegalovirus. The ulcers began to heal after administration of foscarnet sodium. After the treatment, no signs of exacerbation associated with reinstitution of chemotherapy were observed. PMID- 26161052 TI - Utility of the over-the-scope-clip system for treating a large esophageal perforation. AB - We report here a case of esophageal perforation made by an endoscope while treating cicatrical stenosis that developed after wide circumferential dissection of superficial esophageal carcinoma. Perforation closure with a conventional endoclip was difficult as the perforation was large and the surrounding tissue was fragile as a result of steroids administration for stenosis prevention. To avoid surgical intervention, we employed the over-the-scope-clip system and successfully closed the perforation. The favorable outcome suggests the utility of the over-the-scope-clip system for closing perforations when conventional methods are ineffective. PMID- 26161053 TI - Development of Parents' of Children with Hymenoptera Venom Allergy Quality of Life Scale (PoCHVAQoLS). AB - INTRODUCTION: Venom allergy in children, as a potentially life-threatening disease, may have a considerable impact on the quality of life of the parents of the affected patients. AIM: To present development of the quality of life scale for such parents. MATERIAL AND METHODS: The study sample included 70 parents of children with a history of insect sting reaction, referred for consultations to the allergy centre of the University Children's Hospital of Krakow, Krakow, Poland, in 2000-2010. An initial pool of 56 items divided into 6 domains was prepared. The items with intercorrelations higher than 0.7 were removed from each domain and principal component analysis was conducted for each domain separately to provide a one-dimensional subscale for each domain. Reliability of the subscales was assessed using the Cronbach alpha coefficient in terms of the Classical Test Theory and with the rho coefficient in terms of the Item Response Theory. The multidimensionality of the scale was tested using multitrait scaling. RESULTS: Two to four items from each domain were selected to constitute five subscales. Both the rho and alpha coefficients for all the subscales were 0.75 or higher. The multitrait method showed that almost all the items indicated stronger correlations with their own subscale than with other subscales. Correlations between subscales were lower than 0.5. CONCLUSIONS: The presented scale consists of high validity and reliability subscales measuring the quality of life of parents of Hymenoptera venom allergic children. As their quality of life is strongly related to the health of their children, such information may be helpful in everyday clinical practice. PMID- 26161054 TI - Analysis of skin patch test results and metalloproteinase-2 levels in a patient with contact dermatitis. AB - INTRODUCTION: The complex course of skin reactions that contact eczema involves is due in part to abnormalities of the extracellular matrix function. Proteins that degrade extracellular matrix components include metalloproteinases (MMP), which are divided into subcategories depending on the chemical structure and substrate specificity. AIM: To analyse patch test results in contact dermatitis patients and to assess MMP-2 levels during skin lesion exacerbation and remission. MATERIAL AND METHODS: Fifty patients suffering from contact eczema were qualified to the study and 20 healthy volunteers as a control group. The study group patients had epidermal skin tests performed with the "European Standard" set. To assess the MMP-2 level in serum, venous blood was drawn, twice from study group patients - during contact dermatitis exacerbation and remission periods - and once from control group patients. Assessment of MMP-2 in serum was done with ELISA immunoassay. To verify the proposed hypotheses, parametric and nonparametric significance tests were used. RESULTS: Hands were the most frequent location of contact dermatitis. Nickel (II) sulphate was the most frequent sensitizing substance. Mean MMP-2 levels were statistically higher in the study group both in contact dermatitis exacerbation and remission periods than in the control group. There was no statistically significant difference between MMP-2 levels and skin patch test results. CONCLUSIONS: Nickel is one of the most allergenic contact allergens in patients with contact dermatitis. Metalloproteinase-2 is a good marker of contact dermatitis in various stages of the disease. PMID- 26161055 TI - Topical steroid therapy in atopic dermatitis in theory and practice. AB - INTRODUCTION: Topical glucocorticosteroids (GCSs) are commonly used in treatment of atopic dermatitis (AD). AIM: To assess the patients' compliance with the recommended instructions of the therapy. MATERIAL AND METHODS: The study involved 141 adult AD patients. The clinical course of AD and its treatment with GCSs during the last year were analysed. RESULTS: In the periods of exacerbation the lesions involved 10-50% of the skin surface area. Outpatient treatment in specialised dermatological and/or allergology clinics was given to 93% of the study subjects. Sixty-five out of 141 patients regularly attended medical control examinations. Glucocorticosteroids, mostly very potent ones (70.2%), were applied to all the subjects. 66.7% of patients obtained no information about their medications' anti-inflammatory potential. The substances were applied more frequently than twice daily by 36.4% of the patients. Seventy-two of 141 subjects applied GCSs both temporarily and in the long-term treatment, for 8.3 weeks on average. In the long-term treatment, in which very potent GCSs predominated (70.7%), no one used intermittent therapy. One hundred and thirty patients introduced their own modifications to the instructions concerning GCSs use, among which 37.7% changed the site of application, 58.5% prolonged the duration of application and 49.5% shortened it or occasionally temporarily withdrew the prescribed drug. None of the patients knew the fingertip unit method of dose assessment. Apart from steroid therapy, 56.7% of the patients carried out regular care treatment. CONCLUSIONS: The AD patients need to be thoroughly educated by the medical staff in the topical GCSs therapy in atopic dermatitis. PMID- 26161056 TI - Temperament and character profiles of patients with chronic idiopathic urticaria. AB - INTRODUCTION: Psychosocial factors have been implicated as being important in the onset and/or exacerbation of urticaria. AIM: To examine both personality factors of patients with chronic idiopathic urticaria (CIU) and the correlations between illness duration, severity of itching, urticaria activity score (UAS) and temperament-character dimensions. MATERIAL AND METHODS: A total number of 70 CIU patients and 60 healthy individuals were included in the study. The Temperament and Character Inventory (TCI) was administered individually. The relationship between UAS, illness duration and severity of pruritus and TCI subscales were evaluated. RESULTS: The CIU group had significantly higher scores of novelty seeking and lower scores of cooperativeness, reward dependence and self directedness than the control group. CONCLUSIONS: The current study shows that CIU patients have distinctive temperament and character dimensions when compared with the control group. We suggest that evaluation and treatment of CIU should also include psychosomatic approaches in clinical practice. PMID- 26161057 TI - The relation of autologous serum and plasma skin test results with urticarial activity score, sex and age in patients with chronic urticaria. AB - INTRODUCTION: Some previous studies reported autoimmunity as an etiologic factor in chronic urticaria (CU), but the results of some autoimmunity tests in these studies are conflicting. AIM: To concretize whether there was any relation of autologous serum skin test (ASST) and autologous plasma skin test (APST) results with sex, age and urticarial activity score (UAS) in patients with CU. MATERIAL AND METHODS: Fifty patients with CU and twenty healthy subjects admitted to our dermatology clinic were included in the present study. The ASST and APST were applied to all individuals. RESULTS: The positiveness rates of ASST and APST were significantly higher in the patient group than controls (p = 0.027, p = 0.001, respectively). Among patients, the APST positiveness rate (72%) was significantly (p < 0.05) higher than ASST (46%). It was seen that 48% of patients with negative ASST results had positive APST. However, no patient with negative APST results had positive ASST. There were significant (p < 0.05) relations of the tests' positiveness rates with sex and old age but with UAS. The diameter of the erythematous papule was remarkably (p < 0.05) larger in APST than ASST and also significantly (p < 0.05) larger in females compared to males in both tests (p < 0.05). It was positively increased with old age (p < 0.05). CONCLUSIONS: We can suggest that APST is more sensitive than ASST in the assessment of autoimmunity in CU. A high positiveness rate of APST results may be attributed to high numbers of autoantibodies and coagulation factors present in plasma that might probably play a role in etiopathogenesis of CU. PMID- 26161058 TI - Mucocutaneous warts in Middle Anatolia, Turkey: clinical presentations and therapeutic approaches. AB - INTRODUCTION: Viral warts are common skin condition caused by the human papilloma virus. AIM: To determine the clinical features of warts and therapeutic approaches to warts and compare them with the literature. MATERIAL AND METHODS: A cross-sectional survey was conducted on 362 consecutive patients presenting to a dermatology clinic in Ankara, Middle Anatolia, Turkey. Age, gender, anatomic localization, clinical types, number of warts, and medical therapy histories were recorded. RESULTS: In our study 139 (38.4%) children and 223 (61.6%) adults had warts. Warts were seen in 191 men, and 171 women. The mean age was 24.7 +/-13.5. In all groups the incidence and the number of warts were higher in men. Clinical types of warts were vulgar, anogenital, plantar, verruca plana, filiform, and mosaic. Thirty-six (9.9%) of 362 cases had more than one type. The locations of warts were as follows extremities (n = 233, 64.4%), anogenital (n = 86, 23.7%) and head and neck (n = 73, 20.2%). The incidence of anogenital warts was statistically higher in men than women (p < 0.05). Topical medical treatment was the first choice (n = 60, 57.1%). CONCLUSIONS: In our study, the incidence and the number of warts were higher in men, which is different than in previous reports. The anogenital wart (AW) was ranked second in all types of warts. According to this finding, we can say that the frequency of AW has been increased in Turkey. To our knowledge recently there have been no studies investigating the clinical features of viral warts in all ages in the literature. PMID- 26161059 TI - Evaluation of in utero sensitization by screening antigen-specific immunoglobulin E levels in umbilical cord blood. AB - INTRODUCTION: The incidence of asthma and atopic reactions is increasing worldwide. Previous reports have suggested that maternal exposure to allergens during pregnancy may have potential effects on allergic sensitization in infants. AIM: To evaluate the effects of maternal exposure to environmental allergens during pregnancy on in-utero sensitization. MATERIAL AND METHODS: Two hundred mothers and their infants were analyzed in this cross-sectional study. Mothers were given a questionnaire that had a series of questions to evaluate the maternal allergic status and environmental exposures during pregnancy. Plasma specific immunoglobulin E (IgE) levels to pets, grass, food (nuts) of all mothers and their infants were analyzed by an immune-enzymatic assay. RESULTS: There was no significant correlation between plasma specific IgE positivity in mothers, with regard to keeping indoor domestic pets, living in grass habitat, eating nuts in diet. A significant correlation was found between specific IgE presence in mothers and allergic reactions; however, there was no correlation between plasma specific IgE positivity of mothers and infants. CONCLUSIONS: We concluded that prenatal maternal sensitivity to environmental allergens could not be evaluated as a predictive factor for in-utero sensitization. PMID- 26161060 TI - 21-year retrospective study of the prevalence of Scopulariopsis brevicaulis in patients suspected of superficial mycoses. AB - INTRODUCTION: In the genus Scopulariopsis, Scopulariopsis brevicaulis is the most common aetiological agent of infections in humans. It usually affects nails and is one of the commonest moulds associated with onychomycoses. Other forms of infections (skin, subcutaneous, deep tissues, and disseminated infections) have also been described. AIM: To examine the prevalence of S. brevicaulis in clinical materials obtained from patients suspected of keratinized tissues mycoses. MATERIAL AND METHODS: The analysis of the prevalence of S. brevicaulis in clinical specimens was based on mycological test's results carried out for patients who were referred with a suspicion of superficial mycoses to the Department of Mycology, Chair of Microbiology, Jagiellonian University Medical College from 1992 till 2012. RESULTS: In the years 1992-2012 16,815 clinical samples (nail scrapings, nail swabs, skin scrapings, skin swabs, hair) were collected. Pathogenic fungi were detected in 7193 samples and S. brevicaulis was present in 255 (3.5%). The prevalence of S. brevicaulis in males and females was comparable. The species was most often isolated from toenails (80%), both from males and females. In the analysed period we observed a decrease in the prevalence of S. brevicaulis. In most cases (60%) S. brevicaulis occurred alone in 40% of S. brevicaulis positive cultures, other fungi were also isolated. The fungi most frequently isolated with S. brevicaulis were Trichophyton rubrum, T. mentagrophytes, Penicillium sp., Candida sp., and Aspergillus sp. CONCLUSIONS: Scopulariopsis brevicaulis is not a common cause of superficial fungal infections of keratinized tissues, but is a typical mould associated with toenail onychomycosis. A proper identification of this species in onychomycoses is essential for the implementation of effective antifungal therapy. PMID- 26161061 TI - The subjective assessment of the effect and satisfaction with dermocosmetics use by patients with skin disturbances. AB - INTRODUCTION: Atopic dermatitis and different constellations and the severity of symptoms that not meet the criteria for this diagnosis are a common skin disturbances. An important component of the treatment of these diseases and the proper care of sensitive and dry skin is local dermocosmetics use. AIM: To assess the frequency of skin disturbances and the effect and satisfaction with Atoperal products use as well as the source of information about these products. MATERIAL AND METHODS: A questionnaire survey about the type of skin disturbances, the subjective assessment of the effect and satisfaction with Atoperal products use and source of information about these products was performed by 787 general practitioners, internists, pediatricians, dermatologists, allergists and pulmonologists and 252 pharmacists in a group of 51 085 subjects with skin disturbances. RESULTS: In the group interviewed by doctors, the most common skin problem was atopic dermatitis (52.5%) and in the group interviewed by pharmacists, pruritus (70.0%). In both groups, respondents after Atoperal products use most frequently reported improving of the skin hydration and greasiness of the skin and reduction of itching. In both groups, over 90.0% of respondents were satisfied or very satisfied with Atoperal products use. In the group surveyed by doctors, 75.5% of respondents obtained information about these products from doctors and 17.4% from pharmacists, while in the group surveyed by pharmacists, 48.9% from pharmacists and 36.1% from doctors. CONCLUSIONS: Atopic dermatitis was most frequently diagnosed in a group surveyed by doctors. The main skin disturbance that occurred in a group surveyed by pharmacists was skin pruritus. The main effect of Atoperal products use, independent of the place of the survey, included improving of skin hydration and greasiness of the skin and reduction of itching. In a study population, there was a high level of satisfaction from the use of Atoperal products. Doctors and pharmacists were the main sources of information about Atoperal products depending on the place of the survey. PMID- 26161062 TI - Adverse events in allergy sufferers wearing contact lenses. AB - Allergy is the fifth leading chronic condition in industrialized countries among all ages, and the third most common chronic disease among children under 18 years old. Many of allergic patients also have problems with vision and want to improve their quality of life by wearing contact lenses. They are most frequently young and active individuals, for whom contact lenses provide greater convenience and more satisfying vision correction than spectacles. However, application of high quality and immunologically neutral products do not protect from allergic side reactions. Nowadays, eye-related allergy and contact lens wear concern larger and larger populations worldwide. The purpose of this review is to summarize the studies on ocular complications associated with wearing contact lenses. The article presents indications for allergic patients especially on the care system and wear schedule. PMID- 26161063 TI - Selected questionnaire methods studying the quality of life. AB - The scientific literature is full of numerous reports dealing with the quality of life of patients suffering from different diseases. The aim of the study is to present a set of questionnaires, which are used to study the quality of the patient's life, the questionnaires, which are the most popular in Poland and all over the world as well as those which concern the children's allergy. Increasingly, the research deals with the objective and subjective feelings of patients about their condition. Currently, the European Union's priority is to improve the quality of life of patients suffering from chronic non-communicable diseases. The studies on the quality of life are an interdisciplinary area, combining the clinical significance and the psychological aspects of medical care. PMID- 26161064 TI - Cat-scratch disease: a wide spectrum of clinical pictures. AB - The aim of this review is to present an emerging zoonotic disease caused by Bartonella henselae. The wide spectrum of diseases connected with these bacteria varies from asymptomatic cases, to skin inflammation, fever of unknown origin, lymphadenopathy, eye disorders, encephalitis and endocarditis. The reservoirs of B. henselae are domestic animals like cats, guinea pigs, rabbits and occasionally dogs. Diagnosis is most often based on a history of exposure to cats and a serologic test with high titres of the immunoglobulin G antibody to B. henselae. Most cases of cat-scratch disease are self-limited and do not require antibiotic treatment. If an antibiotic is chosen, however, azithromycin has been shown to speed recovery. PMID- 26161065 TI - Basaloid follicular hamartoma on the upper eyelid. PMID- 26161066 TI - Adult onset of multisystem Langerhans cell histiocytosis with skin and lymph node involvement. PMID- 26161067 TI - Mantle cell lymphoma with skin involvement. PMID- 26161068 TI - Pregnancy exacerbates complications of acquired hemophilia in a patient with systemic lupus erythematosus. PMID- 26161069 TI - Behavioral responses to odors from other species: introducing a complementary model of allelochemics involving vertebrates. AB - It has long been known that the behavior of an animal can be affected by odors from another species. Such interspecific effects of odorous compounds (allelochemics) are usually characterized according to who benefits (emitter, receiver, or both) and the odors categorized accordingly (allomones, kairomones, and synomones, respectively), which has its origin in the definition of pheromones, i.e., intraspecific communication via volatile compounds. When considering vertebrates, however, interspecific odor-based effects exist which do not fit well in this paradigm. Three aspects in particular do not encompass all interspecific semiochemical effects: one relates to the innateness of the behavioral response, another to the origin of the odor, and the third to the intent of the message. In this review we focus on vertebrates, and present examples of behavioral responses of animals to odors from other species with specific reference to these three aspects. Searching for a more useful classification of allelochemical effects we examine the relationship between the valence of odors (attractive through to aversive), and the relative contributions of learned and unconditioned (innate) behavioral responses to odors from other species. We propose that these two factors (odor valence and learning) may offer an alternative way to describe the nature of interspecific olfactory effects involving vertebrates compared to the current focus on who benefits. PMID- 26161070 TI - Exploring the role of microglia in mood disorders associated with experimental multiple sclerosis. AB - Microglia is increasingly recognized to play a crucial role in the pathogenesis of psychiatric diseases. In particular, microglia may be the cellular link between inflammation and behavioral alterations: by releasing a number of soluble factors, among which pro-inflammatory cytokines, that can regulate synaptic activity, thereby leading to perturbation of behavior. In multiple sclerosis (MS), the most common neuroinflammatory disorder affecting young adults, microglia activation and dysfunction may account for mood symptoms, like depression and anxiety, that are often diagnosed in patients even in the absence of motor disability. Behavioral studies in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, have shown that emotional changes occur early in the disease and in correlation to inflammatory mediator and neurotransmitter level alterations. However, such studies lack a full and comprehensive analysis of the role played by microglia in EAE-behavioral syndrome. We review the experimental studies addressing behavioral symptoms in EAE, and propose the study of neuron-glia interaction as a powerful but still poorly explored tool to investigate the burden of microglia in mood alterations associated to MS. PMID- 26161071 TI - DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats. AB - Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult born dentate granule cells in rats resulted in accelerated dendritic growth, soma hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function. PMID- 26161072 TI - Lateralized modulation of beta-band power in sensorimotor areas during action observation. AB - The cortical network for action observation includes areas of the visual cortex and non-visual areas, including areas of the motoric system. Parts of this network are known for their contralateral organization during motion execution, i.e., they predominantly control and respond to movements of the contralateral body side. We were interested whether this lateralized organization was also present during action observation. Human participants viewed point-light displays of human actors, where the actor was facing and moving either to the right or to the left, while participants' neuromagnetic activity was recorded using magnetoencephalography (MEG). We found that right and left facing movements elicited different activity in left and right motoric areas. This lateralization effect was found in two distinct spatio-temporal-spectral clusters: An early lateralization effect in medial sensors at 12-16 Hz and ~276-675 ms after stimulus onset, and a second cluster in more lateral sensors at 22-28 Hz and ~1275-1775 ms. Our results demonstrate that in addition to the known somatotopic organization of parts of the human motoric system, these areas also show a lateralization effect during action observation. Thus, our results indicate that the hemispheric organization of one's own body map known for motion execution extends to the visual observation of others' bodily actions and movements. PMID- 26161073 TI - Cognitive and neural strategies during control of the anterior cingulate cortex by fMRI neurofeedback in patients with schizophrenia. AB - Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF) seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC), a central hub for cognitive processing, is one of the brain regions known to be dysfunctional in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI) in patients with schizophrenia to enable them to control their ACC activity. Training was performed over 3 days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI). Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. In a stepwise regression analysis, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, patients with schizophrenia can learn to regulate localized brain activity. However, cognitive strategies and neural network location differ from healthy controls. These data emphasize that for therapeutic interventions in patients with schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social NF based on fMRI may be one method to accomplish precise learning targets. PMID- 26161074 TI - Affective responses after different intensities of exercise in patients with traumatic brain injury. AB - BACKGROUND: Patients with traumatic brain injury (TBI) usually have mood and anxiety symptoms secondary to their brain injury. Exercise may be a cost effective intervention for the regulation of the affective responses of this population. However, there are no studies evaluating the effects of exercise or the optimal intensity of exercise for this clinical group. METHODS: Twelve male patients with moderate or severe TBI [mean age of 31.83 and SD of 9.53] and 12 age- and gender-matched healthy volunteers [mean age of 30.58 and SD of 9.53] participated in two sessions of exercise of high and moderate-intensity. Anxiety and mood was evaluated, and subjective assessment of experience pre- and post exercise was assessed. A mixed between and within-subjects general linear model (GLM) analysis was conducted to compare groups [TBI, control] over condition [baseline, session 1, session 2] allowing for group by condition interaction to be determined. Planned comparisons were also conducted to test study hypotheses. RESULTS: Although no group by condition interaction was observed, planned comparisons indicated that baseline differences between patients and controls in anxiety (Cohens' d = 1.80), tension (d = 1.31), depression (d = 1.18), anger (d = 1.08), confusion (d = 1.70), psychological distress (d = 1.28), and physical symptoms (d = 1.42) disappear after one session of exercise, independently of the intensity of exercise. CONCLUSION: A single-section of exercise, regardless of exercise intensity, had a positive effect on the affective responses of patients with TBI both by increasing positive valence feelings and decreasing negative ones. Exercise can be an easily accessible intervention that may alleviate depressive symptoms related to brain injury. PMID- 26161075 TI - Quantity yields quality when it comes to creativity: a brain and behavioral test of the equal-odds rule. AB - The creativity research community is in search of a viable cognitive measure providing support for behavioral observations that higher ideational output is often associated with higher creativity (known as the equal-odds rule). One such measure has included divergent thinking: the production of many examples or uses for a common or single object or image. We sought to test the equal-odds rule using a measure of divergent thinking, and applied the consensual assessment technique to determine creative responses as opposed to merely original responses. We also sought to determine structural brain correlates of both ideational fluency and ideational creativity. Two-hundred forty-six subjects were subjected to a broad battery of behavioral measures, including a core measure of divergent thinking (Foresight), and measures of intelligence, creative achievement, and personality (i.e., Openness to Experience). Cortical thickness and subcortical volumes (e.g., thalamus) were measured using automated techniques (FreeSurfer). We found that higher number of responses on the divergent thinking task was significantly associated with higher creativity (r = 0.73) as independently assessed by three judges. Moreover, we found that creativity was predicted by cortical thickness in regions including the left frontal pole and left parahippocampal gyrus. These results support the equal-odds rule, and provide neuronal evidence implicating brain regions involved with "thinking about the future" and "extracting future prospects." PMID- 26161076 TI - On the brain-imaging markers of neural correlates of consciousness. PMID- 26161077 TI - Reconstruction and in silico analysis of an Actinoplanes sp. SE50/110 genome scale metabolic model for acarbose production. AB - Actinoplanes sp. SE50/110 produces the alpha-glucosidase inhibitor acarbose, which is used to treat type 2 diabetes mellitus. To obtain a comprehensive understanding of its cellular metabolism, a genome-scale metabolic model of strain SE50/110, iYLW1028, was reconstructed on the bases of the genome annotation, biochemical databases, and extensive literature mining. Model iYLW1028 comprises 1028 genes, 1128 metabolites, and 1219 reactions. One hundred and twenty-two and eighty one genes were essential for cell growth on acarbose synthesis and sucrose media, respectively, and the acarbose biosynthetic pathway in SE50/110 was expounded completely. Based on model predictions, the addition of arginine and histidine to the media increased acarbose production by 78 and 59%, respectively. Additionally, dissolved oxygen has a great effect on acarbose production based on model predictions. Furthermore, genes to be overexpressed for the overproduction of acarbose were identified, and the deletion of treY eliminated the formation of by-product component C. Model iYLW1028 is a useful platform for optimizing and systems metabolic engineering for acarbose production in Actinoplanes sp. SE50/110. PMID- 26161078 TI - Isolation, characterization, and antibiotic resistance of Vibrio spp. in sea turtles from Northwestern Mexico. AB - The aerobic oral and cloacal bacterial microbiota and their antimicrobial resistance were characterized for 64 apparently healthy sea turtles captured at their foraging grounds in Ojo de Liebre Lagoon (OLL), Baja California Sur (BCS), Mexico (Pacific Ocean) and the lagoon system of Navachiste (LSN) and Marine Area of Influence (MAI), Guasave, Sinaloa (Gulf of California). A total of 34 black turtles (Chelonia mydas agassizii) were sampled in OLL and eight black turtles and 22 olive ridley turtles (Lepidochelys olivacea) were sampled in LSN and MAI, respectively from January to December 2012. We isolated 13 different species of Gram-negative bacteria. The most frequently isolated bacteria were Vibrio alginolyticus in 39/64 (60%), V. parahaemolyticus in 17/64 (26%), and V. cholerae in 6/64 (9%). However, V. cholerae was isolated only from turtles captured from the Gulf of California (MAI). Among V. parahaemolyticus strains, six O serogroups and eight serovars were identified from which 5/17 (29.4%) belonged to the pathogenic strains (tdh (+) gene) and 2/17 (11.7%) had the pandemic clone (tdh (+) and toxRS/new (+)). Among V. cholerae strains, all were identified as non O1/non-O139, and in 4/6 (66%) the accessory cholera enterotoxin gene (ace) was identified but without virulence gene zot, ctxA, and ctxB. Of the isolated V. parahaemolyticus, V. cholerae, and V. alginolyticus strains, 94.1, 33.4, and 100% demonstrated resistance to at least one commonly prescribed antibiotic (primarily to ampicillin), respectively. In conclusion, the presence of several potential (toxigenic) human pathogens in sea turtles may represent transmission of environmental microbes and a high-risk of food-borne disease. Therefore, based on the fact that it is illegal and unhealthy, we discourage the consumption of sea turtle meat or eggs in northwestern Mexico. PMID- 26161079 TI - High resolution depth distribution of Bacteria, Archaea, methanotrophs, and methanogens in the bulk and rhizosphere soils of a flooded rice paddy. AB - The communities and abundances of methanotrophs and methanogens, along with the oxygen, methane, and total organic carbon (TOC) concentrations, were investigated along a depth gradient in a flooded rice paddy. Broad patterns in vertical profiles of oxygen, methane, TOC, and microbial abundances were similar in the bulk and rhizosphere soils, though methane and TOC concentrations and 16S rRNA gene copies were clearly higher in the rhizosphere soil than in the bulk soil. Oxygen concentrations decreased sharply to below detection limits at 8 mm depth. Pyrosequencing of 16S rRNA genes showed that bacterial and archaeal communities varied according to the oxic, oxic-anoxic, and anoxic zones, indicating that oxygen is a determining factor for the distribution of bacterial and archaeal communities. Aerobic methanotrophs were maximally observed near the oxic-anoxic interface, while methane, TOC, and methanogens were highest in the rhizosphere soil at 30-200 mm depth, suggesting that methane is produced mainly from organic carbon derived from rice plants and is metabolized aerobically. The relative abundances of type I methanotrophs such as Methylococcus, Methylomonas, and Methylocaldum decreased more drastically than those of type II methanotrophs (such as Methylocystis and Methylosinus) with increasing depth. Methanosaeta and Methanoregula were predominant methanogens at all depths, and the relative abundances of Methanosaeta, Methanoregula, and Methanosphaerula, and GOM_Arc_I increased with increasing depth. Based on contrasts between absolute abundances of methanogens and methanotrophs at depths sampled across rhizosphere and bulk soils (especially millimeter-scale slices at the surface), we have identified populations of methanogens (Methanosaeta, Methanoregula, Methanocella, Methanobacterium, and Methanosphaerula), and methanotrophs (Methylosarcina, Methylococcus, Methylosinus, and unclassified Methylocystaceae) that are likely physiologically active in situ. PMID- 26161080 TI - The link between independent acquisition of intracellular gamma-endosymbionts and concerted evolution in Tremblaya princeps. AB - Many insect species establish mutualistic symbiosis with intracellular bacteria that complement their unbalanced diets. The betaproteobacterium "Candidatus Tremblaya" maintains an ancient symbiosis with mealybugs (Hemiptera: Pseudococcidae), which are classified in subfamilies Phenacoccinae and Pseudococcinae. Most Phenacoccinae mealybugs have "Candidatus Tremblaya phenacola" as their unique endosymbiont, while most Pseudococcinae mealybugs show a nested symbiosis (a bacterial symbiont placed inside another one) where every "Candidatus Tremblaya princeps" cell harbors several cells of a gammaproteobacterium. Genomic characterization of the endosymbiotic consortium from Planococcus citri, composed by "Ca. Tremblaya princeps" and "Candidatus Moranella endobia," unveiled several atypical features of the former's genome, including the concerted evolution of paralogous loci. Its comparison with the genome of "Ca. Tremblaya phenacola" PAVE, single endosymbiont of Phenacoccus avenae, suggests that the atypical reductive evolution of "Ca. Tremblaya princeps" could be linked to the acquisition of "Ca. Moranella endobia," which possess an almost complete set of genes encoding proteins involved in homologous recombination. In order to test this hypothesis, we performed comparative genomics between "Ca. Tremblaya phenacola" and "Ca. Tremblaya princeps" and searched for the co-occurrence of concerted evolution and homologous recombination genes in endosymbiotic consortia from four unexplored mealybug species, Dysmicoccus boninsis, Planococcus ficus, Pseudococcus longispinus, and Pseudococcus viburni. Our results support a link between concerted evolution and nested endosymbiosis. PMID- 26161081 TI - Regulation of adaptive immune responses by guiding cell movements in the spleen. AB - The spleen combines the innate and adaptive immune systems in a uniquely organized way. The excision of spleen will induce many complications, especially the increased susceptibility to infections. Recent research shows that besides playing roles during the immune responses, the spleen is also an important organ during immunoregulation, which is different from other secondary lymphoid organs. This unique function is mainly realized by modulating cell migration and proliferation in the spleen. This review provides a better understanding of the functions of this complex organ gained from recent studies. PMID- 26161083 TI - Single-Dose CpG Immunization Protects Against a Heterosubtypic Challenge and Generates Antigen-Specific Memory T Cells. AB - Despite extensive research, influenza A virus (IAV) remains a major cause of morbidity, mortality, and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains, such as H5N1 and pandemic H1N1, highlight the need for universal, cross-protective vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins, hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are a favorable target for developing vaccines that induce strong T cell responses in addition to humoral immunity. Here, we found that intranasal administration with a single dose of CpG and inactivated x31 (H3N2) reduced viral titers and partially protected mice from a heterosubtypic challenge with a lethal dose of PR8 (H1N1). Early after immunization, vaccinated mice showed increased innate immune activation with high levels of MHCII and CD86 expression on dendritic cells in both draining lymph nodes and lungs. Three days after immunization, CD4 and CD8 cells in the lung upregulated CD69, suggesting that activated lymphocytes are present at the site of vaccine administration. The ensuing effector Th1 responses were capable of producing multiple cytokines and were present at least 30 days after immunization. Furthermore, functional memory responses were observed, as antigen-specific IFN-gamma(+) and GrB(+) cells were detected early after lethal infection. Together, this work provides evidence for using pattern recognition receptor agonists as a mucosal vaccine platform for inducing robust T cell responses capable of protecting against heterologous IAV challenges. PMID- 26161084 TI - Clinical Usefulness of Autoantibodies in Idiopathic Inflammatory Myositis. PMID- 26161082 TI - CD1d Expression and Invariant NKT Cell Responses in Herpesvirus Infections. AB - Invariant natural killer T (iNKT) cells are a highly conserved subset of unconventional T lymphocytes that express a canonical, semi-invariant T cell receptor and surface markers shared with the natural killer cell lineage. iNKT cells recognize exogenous and endogenous glycolipid antigens restricted by non polymorphic CD1d molecules, and are highly responsive to the prototypical agonist, alpha-galactosylceramide. Upon activation, iNKT cells rapidly coordinate signaling between innate and adaptive immune cells through the secretion of proinflammatory cytokines, leading to the maturation of antigen-presenting cells, and expansion of antigen-specific CD4+ and CD8+ T cells. Because of their potent immunoregulatory properties, iNKT cells have been extensively studied and are known to play a pivotal role in mediating immune responses against microbial pathogens including viruses. Here, we review evidence that herpesviruses manipulate CD1d expression to escape iNKT cell surveillance and establish lifelong latency in humans. Collectively, published findings suggest that iNKT cells play critical roles in anti-herpesvirus immune responses and could be harnessed therapeutically to limit viral infection and viral-associated disease. PMID- 26161085 TI - 5-azacytidine promotes microspore embryogenesis initiation by decreasing global DNA methylation, but prevents subsequent embryo development in rapeseed and barley. AB - Microspores are reprogrammed by stress in vitro toward embryogenesis. This process is an important tool in breeding to obtain double-haploid plants. DNA methylation is a major epigenetic modification that changes in differentiation and proliferation. We have shown changes in global DNA methylation during microspore reprogramming. 5-Azacytidine (AzaC) cannot be methylated and leads to DNA hypomethylation. AzaC is a useful demethylating agent to study DNA dynamics, with a potential application in microspore embryogenesis. This work analyzes the effects of short and long AzaC treatments on microspore embryogenesis initiation and progression in two species, the dicot Brassica napus and the monocot Hordeum vulgare. This involved the quantitative analyses of proembryo and embryo production, the quantification of DNA methylation, 5-methyl-deoxy-cytidine (5mdC) immunofluorescence and confocal microscopy, and the analysis of chromatin organization (condensation/decondensation) by light and electron microscopy. Four days of AzaC treatments (2.5 MUM) increased embryo induction, response associated with a decrease of DNA methylation, modified 5mdC, and heterochromatin patterns compared to untreated embryos. By contrast, longer AzaC treatments diminished embryo production. Similar effects were found in both species, indicating that DNA demethylation promotes microspore reprogramming, totipotency acquisition, and embryogenesis initiation, while embryo differentiation requires de novo DNA methylation and is prevented by AzaC. This suggests a role for DNA methylation in the repression of microspore reprogramming and possibly totipotency acquisition. Results provide new insights into the role of epigenetic modifications in microspore embryogenesis and suggest a potential benefit of inhibitors, such as AzaC, to improve the process efficiency in biotechnology and breeding programs. PMID- 26161086 TI - Dynamic proline metabolism: importance and regulation in water limited environments. AB - Drought-induced proline accumulation observed in many plant species has led to the hypothesis that further increases in proline accumulation would promote drought tolerance. Here we discuss both previous and new data showing that proline metabolism and turnover, rather than just proline accumulation, functions to maintain growth during water limitation. Mutants of Delta (1)-Pyrroline-5 Carboxylate Synthetase1 (P5CS1) and Proline Dehydrogenase1 (PDH1), key enzymes in proline synthesis and catabolism respectively, both have similar reductions in growth during controlled soil drying. Such results are consistent with patterns of natural variation in proline accumulation and with evidence that turnover of proline can act to buffer cellular redox status during drought. Proline synthesis and catabolism are regulated by multiple cellular mechanisms, of which we know only a few. An example of this is immunoblot detection of P5CS1 and PDH1 showing that the Highly ABA-induced (HAI) protein phosphatase 2Cs (PP2Cs) have different effects on P5CS1 and PDH1 protein levels despite having similar increases in proline accumulation. Immunoblot data also indicate that both P5CS1 and PDH1 are subjected to unknown post-translational modifications. PMID- 26161087 TI - The genetics of folate metabolism and maternal risk of birth of a child with Down syndrome and associated congenital heart defects. AB - Almost 15 years ago it was hypothesized that polymorphisms of genes encoding enzymes involved in folate metabolism could lead to aberrant methylation of peri centromeric regions of chromosome 21, favoring its abnormal segregation during maternal meiosis. Subsequently, more than 50 small case-control studies investigated whether or not maternal polymorphisms of folate pathway genes could be risk factors for the birth of a child with Down syndrome (DS), yielding conflicting and inconclusive results. However, recent meta-analyses of those studies suggest that at least three of those polymorphisms, namely MTHFR 677C>T, MTRR 66A>G, and RFC1 80G>A, are likely to act as maternal risk factors for the birth of a child with trisomy 21, revealing also complex gene-nutrient interactions. A large-cohort study also revealed that lack of maternal folic acid supplementation at peri-conception resulted in increased risk for a DS birth due to errors occurred at maternal meiosis II in the aging oocyte, and it was shown that the methylation status of chromosome 21 peri-centromeric regions could favor recombination errors during meiosis leading to its malsegregation. In this regard, two recent case-control studies revealed association of maternal polymorphisms or haplotypes of the DNMT3B gene, coding for an enzyme required for the regulation of DNA methylation at centromeric and peri-centromeric regions of human chromosomes, with risk of having a birth with DS. Furthermore, congenital heart defects (CHD) are found in almost a half of DS births, and increasing evidence points to a possible contribution of lack of folic acid supplementation at peri-conception, maternal polymorphisms of folate pathway genes, and resulting epigenetic modifications of several genes, at the basis of their occurrence. This review summarizes available case-control studies and literature meta-analyses in order to provide a critical and up to date overview of what we currently know in this field. PMID- 26161088 TI - Pharmacogenomics of Drug Response in Type 2 Diabetes: Toward the Definition of Tailored Therapies? AB - Type 2 diabetes is one of the major causes of mortality with rapidly increasing prevalence. Pharmacological treatment is the first recommended approach after failure in lifestyle changes. However, a significant number of patients shows-or develops along time and disease progression-drug resistance. In addition, not all type 2 diabetic patients have the same responsiveness to drug treatment. Despite the presence of nongenetic factors (hepatic, renal, and intestinal), most of such variability is due to genetic causes. Pharmacogenomics studies have described association between single nucleotide variations and drug resistance, even though there are still conflicting results. To date, the most reliable approach to investigate allelic variants is Next-Generation Sequencing that allows the simultaneous analysis, on a genome-wide scale, of nucleotide variants and gene expression. Here, we review the relationship between drug responsiveness and polymorphisms in genes involved in drug metabolism (CYP2C9) and insulin signaling (ABCC8, KCNJ11, and PPARG). We also highlight the advancements in sequencing technologies that to date enable researchers to perform comprehensive pharmacogenomics studies. The identification of allelic variants associated with drug resistance will constitute a solid basis to establish tailored therapeutic approaches in the treatment of type 2 diabetes. PMID- 26161089 TI - Comparison of Features for Movement Prediction from Single-Trial Movement-Related Cortical Potentials in Healthy Subjects and Stroke Patients. AB - Detection of movement intention from the movement-related cortical potential (MRCP) derived from the electroencephalogram (EEG) signals has shown to be important in combination with assistive devices for effective neurofeedback in rehabilitation. In this study, we compare time and frequency domain features to detect movement intention from EEG signals prior to movement execution. Data were recoded from 24 able-bodied subjects, 12 performing real movements, and 12 performing imaginary movements. Furthermore, six stroke patients with lower limb paresis were included. Temporal and spectral features were investigated in combination with linear discriminant analysis and compared with template matching. The results showed that spectral features were best suited for differentiating between movement intention and noise across different tasks. The ensemble average across tasks when using spectral features was (error = 3.4 +/- 0.8%, sensitivity = 97.2 +/- 0.9%, and specificity = 97 +/- 1%) significantly better (P < 0.01) than temporal features (error = 15 +/- 1.4%, sensitivity: 85 +/ 1.3%, and specificity: 84 +/- 2%). The proposed approach also (error = 3.4 +/- 0.8%) outperformed template matching (error = 26.9 +/- 2.3%) significantly (P > 0.001). Results imply that frequency information is important for detecting movement intention, which is promising for the application of this approach to provide patient-driven real-time neurofeedback. PMID- 26161090 TI - Vitamin D Status and VDR Genotype in NF1 Patients: A Case-Control Study from Southern Brazil. AB - Neurofibromatosis type 1 (NF1) patients are more likely to have vitamin D deficiency when compared to the general population. This study aimed to determine the levels of 25-OH-vitamin D [25(OH)D] in individuals with NF1 and disease unaffected controls and analyze FokI and BsmI VDR gene polymorphisms in a case and in a control group. Vitamin D levels were compared between a group of 45 NF1 patients from Southern Brazil and 45 healthy controls matched by sex, skin type, and age. Genotypic and allelic frequencies of VDR gene polymorphisms were obtained from the same NF1 patients and 150 healthy controls. 25(OH)D deficiency or insufficiency was not more frequent in NF1 patients than in controls (p = 0.074). We also did not observe an association between FokI and BsmI VDR gene polymorphisms and vitamin D levels in NF1 patients, suggesting that their deficient or insufficient biochemical phenotypes are not associated with these genetic variants. The differences between the groups in genotypic and allelic frequencies for FokI and BsmI VDR gene polymorphisms were small and did not reach statistical significance. These polymorphisms are in partial linkage disequilibrium and the haplotype frequencies also did not differ in a significant way between the two groups (p = 0.613). PMID- 26161091 TI - Analysis of Circulating MicroRNAs In Vivo following Administration of Dexamethasone and Adrenocorticotropin. AB - Purpose. The interaction of hormones of the pituitary-adrenal axis and adrenal cortex-associated circulating microRNAs is mostly unknown. We have studied the effects of dexamethasone and adrenocorticotropin on the expression of five circulating microRNAs (hsa-miR-27a, hsa-miR-200b, hsa-miR-214, hsa-miR-483-5p, and hsa-miR-503) reported to be related to the adrenal cortex in plasma samples. Methods. Expression of microRNAs was studied in plasma samples of 10 individuals examined by 1 mg dexamethasone suppression test and another 10 individuals stimulated by 250 MUg tetracosactide (adrenocorticotropin). Total RNA was isolated and microRNA expression was analyzed by real-time reverse transcription quantitative polymerase chain reaction normalized to cel-miR-39 as reference. Results. Only circulating hsa-miR-27a proved to be significantly modulated in vivo by hormonal treatments: its expression was upregulated by dexamethasone whereas it was suppressed by adrenocorticotropin. Secreted hsa-miR-27a was significantly induced by dexamethasone in vitro in NCI-H295R cells, as well. The expression of hsa-miR-483-5p proposed as diagnostic marker for adrenocortical malignancy was not affected by dexamethasone or tetracosactide administration. Conclusions. hsa-miR-27a expression is modulated by hormones of the hypothalamic pituitary-adrenal axis both in vitro and in vivo. The biological relevance of hsa miR-27a modulation by hormones is unclear, but the responsiveness of circulating microRNAs to hormones of the pituitary-adrenal axis is noteworthy. PMID- 26161092 TI - Gender-Specific Effect of -102G>A Polymorphism in Insulin Induced Gene 2 on Obesity in Chinese Children. AB - Background. Insulin induced gene 2 (INSIG2) encodes a protein that has a biological effect on regulation of adipocyte metabolism and body weight. This study aimed to investigate the association of INSIG2 gene -102G>A polymorphism with obesity related phenotypes in Chinese children and test gender-specific effects. Methods. The 2,030 independent individuals aged from 7 to 18 years, including 705 obese cases and 1,325 nonobese controls, were recruited from local schools. We measured the obesity-related phenotypes and detected the serum lipids. We genotype -102G>A polymorphism by using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results. In all individuals, we found that the GG/GA genotype of INSIG2 -102G>A polymorphism was associated with risk of severe obesity (OR = 1.62, 95% CI: 1.11 2.36, and P = 0.012) under the dominant model. The association with severe obesity existed only in boys (OR = 1.91, 95% CI: 1.15-3.17, P = 0.012). The GG/GA genotype of -102G>A polymorphism was also associated with higher waist circumference (beta = 2.61 cm, P = 0.031) in boys. No similar association was found in girls. The polymorphism was not associated with other obesity-related phenotypes, neither in all individuals nor in gender-specific population. Conclusions. This study identified a gender-specific effect of INSIG2 -102G>A polymorphism on risk of severe obesity and waist circumference in Chinese boys. PMID- 26161093 TI - In Vitro Ability of a Novel Nanohydroxyapatite Oral Rinse to Occlude Dentine Tubules. AB - Objectives. The aim of the study was to investigate the ability of a novel nanohydroxyapatite (nHA) desensitizing oral rinse to occlude dentine tubules compared to selected commercially available desensitizing oral rinses. Methods. 25 caries-free extracted molars were sectioned into 1 mm thick dentine discs. The dentine discs (n = 25) were etched with 6% citric acid for 2 minutes and rinsed with distilled water, prior to a 30-second application of test and control oral rinses. Evaluation was by (1) Scanning Electron Microscopy (SEM) of the dentine surface and (2) fluid flow measurements through a dentine disc. Results. Most of the oral rinses failed to adequately cover the dentine surface apart from the nHa oral rinse. However the hydroxyapatite, 1.4% potassium oxalate, and arginine/PVM/MA copolymer oral rinses, appeared to be relatively more effective than the nHA test and negative control rinses (potassium nitrate) in relation to a reduction in fluid flow measurements. Conclusions. Although the novel nHA oral rinse demonstrated the ability to occlude the dentine tubules and reduce the fluid flow measurements, some of the other oral rinses appeared to demonstrate a statistically significant reduction in fluid flow through the dentine disc, in particular the arginine/PVM/MA copolymer oral rinse. PMID- 26161094 TI - Preliminary In Vitro Assessment of Stem Cell Compatibility with Cross-Linked Poly(epsilon-caprolactone urethane) Scaffolds Designed through High Internal Phase Emulsions. AB - By using a high internal phase emulsion process, elastomeric poly(epsilon caprolactone urethane) (PCLU) scaffolds were designed with pores size ranging from below 150 MUm to 1800 MUm and a porosity of 86% making them suitable for bone tissue engineering applications. Moreover, the pores appeared to be excellently interconnected, promoting cellularization and future bone ingrowth. This study evaluated the in vitro cytotoxicity of the PCLU scaffolds towards human mesenchymal stem cells (hMSCs) through the evaluation of cell viability and metabolic activity during extract test and indirect contact test at the beginning of the scaffold lifetime. Both tests demonstrated that PCLU scaffolds did not induce any cytotoxic response. Finally, direct interaction of hMSCs and PCLU scaffolds showed that PCLU scaffolds were suitable for supporting the hMSCs adhesion and that the cells were well spread over the pore walls. We conclude that PCLU scaffolds may be a good candidate for bone tissue regeneration applications using hMSCs. PMID- 26161096 TI - Non-culprit lesion percutaneous coronary intervention during acute myocardial infarction - the road not taken? PMID- 26161095 TI - Adherence to Artemisinin-Based Combination Therapy for the Treatment of Uncomplicated Malaria: A Systematic Review and Meta-Analysis. AB - Adherence to artemisinin-based combination therapy (ACT) is not clearly defined. This meta-analysis determines the prevalence and predictors of adherence to ACT. Twenty-five studies and six substudies met the inclusion criteria. The prevalence of ACT adherence in the public sector was significantly higher compared to retail sector (76% and 45%, resp., P < 0.0001). However, ACT adherence was similar across different ACT dosing regimens and formulations. In metaregression analysis prevalence estimates of adherence significantly decrease with increasing year of study publication (P = 0.046). Factors found to be significant predictors of ACT adherence were years of education >= 7 {odds ratio (OR) (95% CI) = 1.63 (1.05 2.53)}, higher income {2.0 (1.35-2.98)}, fatty food {4.6 (2.49-8.50)}, exact number of pills dispensed {4.09 (1.60-10.7)}, and belief in traditional medication for malaria {0.09 (0.01-0.78)}. The accuracy of pooled estimates could be limited by publication bias, and differing methods and thresholds of assessing adherence. To improve ACT adherence, educational programs to increase awareness and understanding of ACT dosing regimen are interventions urgently needed. Patients and caregivers should be provided with an adequate explanation at the time of prescribing and/or dispensing ACT. PMID- 26161098 TI - Complete infarct-related artery revascularization in acute myocardial infarction patients. CORAMI Registry. AB - INTRODUCTION: There are still limited data on the occurrence of multiple stenotic lesions within the infarct-related artery (IRA) in acute myocardial infarction (MI), and there is no consensus on the optimal treatment of this patient subgroup, which varies between centers and operators. AIM: To analyse the clinical efficacy of percutaneous coronary intervention (PCI) strategy of culprit lesion only in patients with myocardial infarction. MATERIAL AND METHODS: Patients with acute MI with the presence of at least two significant lesions in the IRA - (1) the target culprit lesion which required immediate stenting (> 50 100% stenosis) and (2) a second distal critical lesion (70-90%) - were included in the registry. Both lesions in the IRA were considered to be independent lesions requiring two separate stent platforms to be covered (no overlap). The decision on the treatment strategy of either complete (CR) or culprit-lesion-only (CLO) revascularization was at the discretion of the operator. RESULTS: There were altogether 95 patients enrolled in the registry, 63 (66%) in the group with CR of the IRA and 32 (34%) with CLO revascularization, which did not differ in terms of baseline demographics. In-hospital and long-term outcomes were similar between the groups. Stent thrombosis at 1 year occurred in 1.6% in CR and in 6.2% in CLO groups respectively (statistically not significant). There were no patients from the CLO group who had a planned percutaneous coronary intervention (PCI) of the 2(nd) lesion in the IRA during 1-year observation. CONCLUSIONS: At 1 year the clinical outcome was similar between those with complete and CLO PCI. Complete coverage of significant lesions did not increase the risk of stent thrombosis or need for repeated revascularization in long-term observation. PMID- 26161097 TI - The basics of intravascular optical coherence tomography. AB - Optical coherence tomography (OCT) has opened new horizons for intravascular coronary imaging. It utilizes near-infrared light to provide a microscopic insight into the pathology of coronary arteries in vivo. Optical coherence tomography is also capable of identifying the chemical composition of atherosclerotic plaques and detecting traits of their vulnerability. At present it is the only tool to measure the thickness of the fibrous cap covering the lipid core of the atheroma, and thus it is an exceptional modality to detect plaques that are prone to rupture (thin fibrous cap atheromas). Moreover, it facilitates distinguishing between plaque rupture and plaque erosion as a cause of acute intracoronary thrombosis. Optical coherence tomography is applied to guide angioplasties of coronary lesions and to assess outcomes of percutaneous coronary interventions broadly. It identifies stent malapposition, dissections, and thrombosis with unprecedented precision. Furthermore, OCT helps to monitor vessel healing after stenting. It evaluates the coverage of stent struts by the neointima and detects in-stent neoatherosclerosis. With so much potential, new studies are warranted to determine OCT's clinical impact. The following review presents the technical background, basics of OCT image interpretation, and practical tips for adequate OCT imaging, and outlines its established and potential clinical application. PMID- 26161099 TI - Knowledge of chronic total occlusion among Polish interventional cardiologists. AB - INTRODUCTION: Chronic total occlusion (CTO) recanalization is indicated in patients with symptoms and evidence of ischemia, but in most cases those types of lesions are still treated medically. In the last few years CTO angioplasty technique has changed dramatically due to considerable advances in techniques and dedicated equipment. AIM: An attempt to assess the state of knowledge of technical aspects of CTO angioplasty of coronary arteries among Polish interventional cardiologists. MATERIAL AND METHODS: Questionnaire survey performed during two major Polish invasive cardiology workshops. RESULTS: In the study there participated 113 physicians with an average length of work experience of 13 years, most of them cardiologists certified as independent primary operators. The majority of respondents recognized the need of prevention of thrombotic complications through control of activated coagulation time during the CTO procedures. Prevention of renal complications and X-ray protection are also recognized as a significant part of the procedures. The benefits from the use of over-the-wire microcatheters and balloons, the proper choice of dedicated guidewires, contralateral injections and retrograde technique are underestimated. CONCLUSIONS: Despite satisfactory knowledge about indications and qualification for the CTO procedure, the awareness of procedural aspects (particularly the retrograde technique) as well as the dedicated CTO equipment among Polish interventional cardiologists is still insufficient. PMID- 26161100 TI - Echocardiographic evaluation of myocardial strain in patients after transcatheter aortic valve implantation. AB - INTRODUCTION: Echocardiographic evaluation of regional myocardial function helps to assess the efficacy of therapeutic interventions and to predict the prognosis and clinical outcomes. AIM: To assess whether myocardial strain can be useful in estimation of left ventricle (LV) function in patients who have undergone transcatheter aortic valve implantation (TAVI). MATERIAL AND METHODS: Twenty-six patients with severe aortic stenosis, who successfully underwent TAVI, were enrolled in the study. Left ventricular peak systolic longitudinal strain (LV PSLS) was obtained before and 1 year after the procedure. Analysis included the potent influence of factors such as sex, LV ejection fraction (LVEF), type of prosthesis implanted or the type of the approach on LV PSLS values. RESULTS: We observed a significant improvement in LV PSLS values after TAVI (-10.9 +/-5.7 vs. -13.4 +/-4.7, p < 0.05). Men had better improvement in LV PSLS after TAVI, but their starting values were considerably lower (M: -10.7 +/-4.5 before vs. -13.3 +/-4.9 after, p < 0.05; W: -11.8 +/-6.8 before vs. -11.9 +/-5.6 after, p = NS). Patients with starting LVEF <= 40% benefited from the procedure (LV PSLS: -10.3 +/-6.4 before vs. -13.7 +/-2.9 after, p < 0.05), but in the group of patients with the higher starting LVEF no significant changes in LV PSLS were observed. We also did not note any differences in LV PSLS depending on type of the prosthesis implemented (Edwards Sapiens/CoreValve). Patients in whom the prostheses were implemented via the femoral approach only presented significant increase in LV PSLS values (before: -10.4 +/-6.7 vs. after: -13.6 +/-3.7, p < 0.05). CONCLUSIONS: The TAVI results in improvement of LV systolic function according to LV PSLS values. Some factors, especially lower baseline LVEF, are related to increased benefit in LV PSLS after TAVI. PMID- 26161101 TI - Myocardial regeneration strategy using Wharton's jelly mesenchymal stem cells as an off-the-shelf 'unlimited' therapeutic agent: results from the Acute Myocardial Infarction First-in-Man Study. AB - INTRODUCTION: In large-animal acute myocardial infarction (AMI) models, Wharton's jelly (umbilical cord matrix) mesenchymal stem cells (WJMSCs) effectively promote angiogenesis and drive functional myocardial regeneration. Human data are lacking. AIM: To evaluate the feasibility and safety of a novel myocardial regeneration strategy using human WJMSCs as a unique, allogenic but immuno privileged, off-the-shelf cellular therapeutic agent. MATERIAL AND METHODS: The inclusion criterion was first, large (LVEF <= 45%, CK-MB > 100 U/l) AMI with successful infarct-related artery primary percutaneous coronary intervention reperfusion (TIMI >= 2). Ten consecutive patients (age 32-65 years, peak hs troponin T 17.3 +/-9.1 ng/ml and peak CK-MB 533 +/-89 U/l, sustained echo LVEF reduction to 37.6 +/-2.6%, cMRI LVEF 40.3 +/-2.7% and infarct size 20.1 +/-2.8%) were enrolled. RESULTS: 30 * 10(6) WJMSCs were administered (LAD/Cx/RCA in 6/3/1) per protocol at ~ 5-7 days using a cell delivery-dedicated, coronary-non occlusive method. No clinical symptoms or ECG signs of myocardial ischemia occurred. There was no epicardial flow or myocardial perfusion impairment (TIMI-3 in all; cTFC 45 +/-8 vs. 44 +/-9, p = 0.51), and no patient showed hs-troponin T elevation (0.92 +/-0.29 <= 24 h before vs. 0.89 +/-0.28 <= 24 h after; decrease, p = 0.04). One subject experienced, 2 days after cell transfer, a transient temperature rise (38.9 degrees C); this was reactive to paracetamol with no sequel. No other adverse events and no significant arrhythmias (ECG Holter) occurred. Up to 12 months there was one new, non-index territory lethal AMI but no adverse events that might be attributable to WJMSC treatment. CONCLUSIONS: This study demonstrated the feasibility and procedural safety of WJMSC use as off the-shelf cellular therapy in human AMI and suggested further clinical safety of WJMSC cardiac transfer, providing a basis for randomized placebo-controlled endpoint-powered evaluation. PMID- 26161102 TI - The association between periprocedural factors and the late outcome of percutaneous stenting of lower extremity arteries. A retrospective cohort study. AB - INTRODUCTION: About 20-30% of the population have peripheral artery disease. Many of them require intervention, with a percutaneous procedure currently being the first choice. However, the outcomes of these interventions need regular evaluation due to continuous progress in endovascular techniques and the devices used. AIM: The aim of this study was to analyze procedural factors influencing the outcome of endovascular intervention in patients stented for the first time due to lower extremity atherosclerosis. MATERIAL AND METHODS: The medical documentation of 91 patients with at least 1 year of follow-up after stenting of a lower limb artery was retrospectively evaluated. Uni- and multivariate analyses were performed. RESULTS: The mean observation time was 544.4 +/-502.9 days. The primary patency of a stent after such a follow-up was 68.1%. Cox proportional hazard analysis revealed that the risk of target lesion revascularization was affected by the following (hazard risk, 95% confidence interval): the number of vascular segments with significant lesions (13.14, 2.28-75.8); critical limb ischemia (5.68, 1.23-26.2); localization of the target lesion in an aorto-iliac in comparison with a femoro-popliteal vascular segment (0.37, 0.14-0.7); aorto iliac lesion class according to the TASC-II consensus (1.96, 1.1-3.8); and claudication distance (1.02, 1.01-1.03). CONCLUSIONS: The common primary patency of a stent implanted into either an aorto-iliac or a femoro-popliteal vascular segment was similar to that found in other reports. The main factors affecting the outcome of the endovascular procedures performed were mainly related to atherosclerosis severity, not to the type of technique or device used. PMID- 26161103 TI - Clinical and morphological features of patients who underwent endovascular interventions for lower extremity arterial occlusive diseases. AB - INTRODUCTION: Patients with peripheral arterial disease (PAD) are at increased risk for all-cause mortality and cardiovascular mortality. AIM: To present anatomical and morphological characteristics of patients who underwent endovascular stenting with laboratory and our mid-term results. MATERIAL AND METHODS: One hundred fifty-three patients (mean age: 62.8, 86% male) who underwent percutaneous intervention of lower extremity arteries were included in the study. Demographic characteristics, medical history, physical examination and laboratory findings of patients were analyzed. Patients' lesions were classified according to the TransAtlantic Inter-Society Consensus (TASC). Clinical outcomes included complications and mortality, 6-minute walking distance, functional class (NYHA) and patency rates. RESULTS: Seventy percent of patients had hypertension, 42% were smokers, 78% had coronary artery disease, 20% had coronary artery bypass grafting, 55% had diabetes mellitus and 71% had dyslipidemia. Six patients with diabetes mellitus and poor wound healing despite medical therapy were treated with stenting leading to alleviation of pain and avoidance of amputation. The initial technical success rate of revascularization was 95.6% (153/160). Our mid term results show that percutaneous procedures in lower extremity arterial diseases can be performed with low complication and high success rates. Patients' 6-minute walk distance, ankle/brachial index values, functional class and the status of foot ulcers were evaluated. CONCLUSIONS: Especially in patients with distal vascular disease, poor wound healing and no chance of surgical revascularization, percutaneous endovascular revascularization may provide good blood flow and prevent amputation. PMID- 26161104 TI - Invasive treatment for carotid fibromuscular dysplasia. AB - INTRODUCTION: Fibromuscular dysplasia (FMD) is an infrequent non-inflamatory disease of unknown etiology that affects mainly medium-size arteries. The prevalence of FMD among patients scheduled for endovascular treatment of carotid artery stenosis is unknown. AIM: To evaluate the prevalence and treatment options of carotid FMD in patients scheduled for carotid artery stenting (CAS). MATERIAL AND METHODS: Between Jan 2001 and Dec 2013, 2012 CAS procedures were performed in 1809 patients (66.1% men; age 65.3 +/-8.4 years, 49.2% symptomatic). In case of FMD suspicion in Doppler-duplex ultrasound (DUS), computed tomography angiography was performed for aortic arch and extracranial and intracranial artery imaging. For invasive treatment of FMD carotid stenosis, balloon angioplasty was considered first. If the result of balloon angioplasty was not satisfactory (> 30% residual stenosis, dissection), stent placement was scheduled. All patients underwent follow-up DUS and neurological examination 3, 6 and 12 months after angioplasty, then annually. RESULTS: There were 7 (0.4%) (4 symptomatic) cases of FMD. The FMD group was younger (47.9 +/-7.5 years vs. 67.2 +/-8.9 years, p = 0.0001), with higher prevalence of women (71.4% vs. 32.7%, p = 0.0422), a higher rate of dissected lesions (57.1% vs. 4.6%, p = 0.0002) and less severe stenosis (73.4% vs. 83.9%, p = 0.0070) as compared to the non-FMD group. In the non-FMD group the prevalence of coronary artery disease was higher (65.1% vs. 14.3% in FMD group, p = 0.009). All FMD patients underwent successful carotid artery angioplasty with the use of neuroprotection devices. In 4 cases angioplasty was supported by stent implantation. CONCLUSIONS: Fibromuscular dysplasia is rare among patients referred for CAS. In case of significant FMD carotid stenosis, it may be treated with balloon angioplasty (stent supported if necessary) with optimal immediate and long-term results. PMID- 26161106 TI - Early occlusion of the non-infarct-related coronary artery following successful primary percutaneous coronary intervention in ST-elevation myocardial infarction. AB - We present a clinical case of early occlusion of the non-infarct-related artery (non-IRA) in a patient with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Several hours after successful percutaneous treatment of the occluded right coronary artery the patient developed a second myocardial infarction, which was caused by acute occlusion of the left anterior descending artery, which had a significant lesion in the proximal segment. The lesion was diagnosed during the first catheterization, but was left untreated. We discuss the potential advantages and risks associated with the ad-hoc multivessel PCI strategy in STEMI. PMID- 26161105 TI - The relationship between neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and thrombolysis in myocardial infarction risk score in patients with ST elevation acute myocardial infarction before primary coronary intervention. AB - INTRODUCTION: The thrombolysis in myocardial infarction (TIMI) risk score is calculated as the sum of independent predictors of mortality and ischemic events in ST elevation acute myocardial infarction (STEMI). Several studies show that the neutrophil to lymphocyte ratio (NLR) is a prognostic inflammatory marker. In preliminary studies, platelet to lymphocyte ratio (PLR) has been proposed as a pro-thrombotic marker. The relationship between NLR, PLR and TIMI risk score for STEMI has never been studied. AIM: To evaluate the association between TIMI-STEMI risk score and NLR, PLR and other biochemical indices in STEMI. MATERIAL AND METHODS: In this retrospective study, we evaluated 390 patients who presented with STEMI within 12 h of symptom onset. Patients were grouped according to low and high TIMI risk scores. RESULTS: We enrolled 390 patients (mean age 61.9 +/ 13.6 years; 73% were men). The NLR, platelet distribution width (PDW) and uric acid level (UA) were significantly associated with a high TIMI-STEMI risk score (p = 0.016, p = 0.008, p = 0.030, respectively), but PLR was not associated with a high TIMI-STEMI risk score. Left ventricular ejection fraction was an independent predictor of TIMI-STEMI risk score. A cut-off point of TIMI-STEMI score of > 4 predicted in-hospital mortality (sensitivity 75%, specificity 70%, p < 0.001). We found that NLR, PDW, and UA level were associated with TIMI-STEMI risk score. CONCLUSIONS: Neutrophil to lymphocyte ratio, PDW and UA level are convenient, inexpensive and reproducible biomarkers for STEMI prognosis before primary angioplasty when these indicators are combined with the TIMI-STEMI risk score. We believe that these significant findings can guide further clinical practice. PMID- 26161107 TI - Immunosuppressive therapy induced coronary vasospasm and acute myocardial infarction in a patient undergoing new renal transplantation. AB - Immunosuppressant agents such as calcineurin inhibitors (CNI) used after solid organ transplantation may cause endothelial dysfunction, and coronary and renal arterial vasospasm. We report a patient presenting acute ST segment elevation myocardial infarction (STEMI) at the second week of renal transplantation. In the case of STEMI in patients with solid organ transplants under immunosuppressive therapy with CNI, coronary vasospasm associated with these drugs should be kept in mind before starting any interventional procedure. High dose nitroglycerine may immediately resolve tacrolimus or cyclosporine A induced coronary vasospasm. Calcium channel blockers should immediately be added to treatment because of the short half-life of nitroglycerine. PMID- 26161108 TI - Posttraumatic infrarenal abdominal aortic pseudoaneurysm treated with bifurcated endovascular graft stent. AB - Posttraumatic infrarenal aortic pseudoaneurysms are rare and potentially lethal lesions. We report the case of a 32-year-old man presenting with infrarenal aortic pseudoaneurysm eight months after being stabbed in the back and right flank. His pseudoaneurysm was close to the iliac bifurcation, so we decided to deploy a bifurcated endovascular graft stent, the TriVascular Ovation endovascular stent. Imaging one month after the procedure revealed no endoleak and slight shrinkage of the pseudoaneurysm. PMID- 26161109 TI - Transradial percutaneous coronary intervention for unprotected left main closure during acute myocardial infarction. PMID- 26161110 TI - Sequential contralateral injection through the same transradial vascular approach in a chronic total occlusion. PMID- 26161111 TI - Patient-prosthesis mismatch after mitral valve-in-valve procedure - at the cost of life or serious consequence? PMID- 26161112 TI - Transcatheter aortic paravalvular leak closure using 3 Amplatzer Vascular Plug III devices in a child. PMID- 26161113 TI - Successful device closure in a congenital Gerbode defect. PMID- 26161114 TI - Do physicians think genomic medicine will be useful for patient care? AB - Significant technological improvements over the last decade have led to a vast expansion in the understanding of the genomic architecture of human disease. However, the use of genomic information, so-called genomic medicine, in routine clinical care, has been slow in comparison to the growth in genomic discovery. The uptake of genomic technology into clinical practice will depend on physicians' perspectives of its utility in patient care. We review recent literature addressing physician attitudes regarding the usefulness and limitations of genomic testing. We conclude by proposing research areas to better understand the role physicians will play in the uptake of genomic information into clinical medicine. PMID- 26161115 TI - Antimicrobial Activity of the Essential Oil of Plectranthus neochilus against Cariogenic Bacteria. AB - This work used the broth microdilution method to investigate the antimicrobial activity of the essential oil obtained from the leaves of Plectranthus neochilus (PN-EO) against a representative panel of oral pathogens. We assessed the antimicrobial activity of this oil in terms of the minimum inhibitory concentration (MIC). PN-EO displayed moderate activity against Enterococcus faecalis (MIC = 250 MUg/mL) and Streptococcus salivarus (MIC = 250 MUg/mL), significant activity against Streptococcus sobrinus (MIC = 62.5 MUg/mL), Streptococcus sanguinis (MIC = 62.5 MUg/mL), Streptococcus mitis (MIC = 31.25 MUg/mL), and Lactobacillus casei (MIC = 31.25 MUg/mL), and interesting activity against Streptococcus mutans (MIC = 3.9 MUg/mL). GC-FID and GC-MS helped to identify thirty-one compounds in PN-EO; alpha-pinene (1, 14.1%), beta-pinene (2, 7.1%), trans-caryophyllene (3, 29.8%), and caryophyllene oxide (4, 12.8%) were the major chemical constituents of this essential oil. When tested alone, compounds 1, 2, 3, and 4 were inactive (MIC > 4000 MUg/mL) against all the microorganisms. These results suggested that the essential oil extracted from the leaves of Plectranthus neochilus displays promising activity against most of the evaluated cariogenic bacteria, especially S. mutans. PMID- 26161116 TI - The Study of Dynamic Characteristic of Acupoints Based on the Primary Dysmenorrhea Patients with the Tenderness Reflection on Diji (SP 8). AB - In TCM theory, acupoint is not a fixed point but a portal with dynamic characteristics where the channel qi enters and flows out. The dynamic characteristics have been verified primarily by detecting the tenderness reaction on Diji (SP 8) in primary dysmenorrhea patients. In this study, finger pressing and algometer were applied in Diji (SP 8) area of participants in menstrual period and nonmenstrual period, respectively, to detect the tenderness occurrence rate, the VAS score of the tenderest point, the tenderness threshold of the tenderest point, and the location of the tenderest point. The result suggests that the acupoint may not be a fixed location but a point in a dynamic state within a certain range in time and space varying with different physiological and pathological status. PMID- 26161117 TI - Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study. AB - Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP) model and functional magnetic resonance imaging (fMRI) to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP) and once during tactile stimulation (SHAM) pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo) values in the pain matrix, limbic system, and default mode network (DMN) and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind body therapy for ALBP. PMID- 26161118 TI - Effect of Ginseng (Panax ginseng) Berry EtOAc Fraction on Cognitive Impairment in C57BL/6 Mice under High-Fat Diet Inducement. AB - High-fat diet-induced obesity leads to type 2 diabetes. Recently, there has been growing apprehension about diabetes-associated cognitive impairment (DACM). The effect of ginseng (Panax ginseng) berry ethyl acetate fraction (GBEF) on mice with high-fat diet-induced cognitive impairment was investigated to confirm its physiological function. C57BL/6 mice were fed a high-fat diet for 5 weeks and then a high-fat diet with GBEF (20 and 50 mg/kg of body weight) for 4 weeks. After three in vivo behavioral tests (Y-maze, passive avoidance, and Morris water maze tests), blood samples were collected from the postcaval vein for biochemical analysis, and whole brains were prepared for an ex vivo test. A method based on ultra-performance liquid chromatography (UPLC) accurate-mass quadrupole time-of flight mass spectrometry (Q-TOF/MS) was used to determine major ginsenosides. GBEF decreased the fasting blood glucose levels of high-fat diet-induced diabetes mellitus (DM) mice and improved hyperglycemia. Cognitive behavior tests were examined after setting up the DM mice. The in vivo experiments showed that mice treated with GBEF exhibited more improved cognitive behavior than DM mice. In addition, GBEF effectively inhibited the acetylcholinesterase (AChE) activity and malondialdehyde (MDA) levels of DM mice brain tissues. Q-TOF UPLC/MS analyses of GBEF showed that ginsenoside Re was the major ginsenoside. PMID- 26161120 TI - Changes in the Composition of Aromatherapeutic Citrus Oils during Evaporation. AB - The composition of some commercial Citrus oils, lemon, sweet orange, and tangerine, designated for aromatherapy, was examined before and after partial evaporation in a stream of nitrogen. The intact oils contained the expected mixtures of mono- and sesquiterpenes, with hydrocarbons dominating and lesser amounts of oxygenated analogues making up the remainder. Gas chromatography-mass spectrometry was used to follow alterations in the relative amounts of the various components present as evaporation proceeded. Changes were marked, and in particular more volatile components present in the intact oils rapidly disappeared. Thus the balance of content was shifted away from monoterpene hydrocarbons towards the analogous alcohols and carbonyl compounds. The results of this differential evaporation are discussed and possible consequences for aromatherapy use are noted. The case of lemon oil was especially interesting as the relative amount of citral, a known sensitizer, remaining as time elapsed represented an increasing percentage of the total oil. PMID- 26161119 TI - Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells. AB - Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 uM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARbeta, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy. PMID- 26161121 TI - Function of Nucleus Ventralis Posterior Lateralis Thalami in Acupoint Sensitization Phenomena. AB - To observe the effect of electroacupuncture (EA) on nucleus ventralis posterior lateralis (VPL) thalami activated by visceral noxious stimulation and to explore the impact of EA on the mechanism of acupoint sensitization under a pathological state of the viscera, EA was applied at bilateral "Zusanli-Shangjuxu" acupoints. The discharge of VPL neurons was response to EA increased after colorectal distension (CRD). The stimulation at "Zusanli-Shangjuxu" acupoints enhanced discharge activity of VPL neurons under CRD-induced visceral pain. The frequency of neuronal discharge was associated with the pressure gradient of CRD which showed that visceral noxious stimulation may intensify the body's functional response to stimulation at acupoints. PMID- 26161122 TI - Antiproliferative Effect of Rottlerin on Sk-Mel-28 Melanoma Cells. AB - Melanoma is the most aggressive and chemoresistant form of skin cancer. Mutated, constitutively active B-RAF is believed to play a crucial role, although the selective B-RAF inhibition has shown poor clinical success, since phenomena of resistance usually occur, likely arising from additional genetic aberrations, such as loss of function of p53 and PTEN, overexpression of cyclin D1, hyperactivation of NF-kappaB, and downregulation of p21/Cip1. Since all of them are present in the Sk-Mel-28 melanoma cells, this cell line could be an ideal, albeit hard to study, model to develop new therapeutic strategies. In the current study, we tested the cytostatic action of Rottlerin on Sk-Mel-28 melanoma cells, on the basis of the known Rottlerin effects on the main proliferative signaling pathways. We presented evidence that the drug inhibits cell growth by an Akt- and p21/Cip1-independent mechanism, involving the dual inhibition of ERK and NF kappaB and downregulation of cyclin D1. In addition, we found that Rottlerin increases ERK phosphorylation, but, surprisingly, this resulted in decreased ERK activity. Pull-down experiments, using Rottlerin-CNBr-conjugated Sepharose beads, revealed that Rottlerin binds to ERK, independently from its phosphorylation status. This direct interaction could in part explain the paradoxical blockage of ERK downstream signaling and growth arrest. We would like to dedicate this paper to the memory of our friend and colleague, prematurely deceased, Claudia Torricelli, who actively contributed to this project. PMID- 26161123 TI - Effect of Repeated Electroacupuncture Intervention on Hippocampal ERK and p38MAPK Signaling in Neuropathic Pain Rats. AB - Results of our past studies showed that hippocampal muscarinic acetylcholine receptor (mAChR)-1 mRNA and differentially expressed proteins participating in MAPK signaling were involved in electroacupuncture (EA) induced cumulative analgesia in neuropathic pain rats, but the underlying intracellular mechanism remains unknown. The present study was designed to observe the effect of EA stimulation (EAS) on hippocampal extracellular signal-regulated kinases (ERK) and p38 MAPK signaling in rats with chronic constrictive injury (CCI) of the sciatic nerve, so as to reveal its related intracellular targets in pain relief. After CCI, the thermal pain thresholds of the affected hind were significantly decreased compared with the control group (P < 0.05). Following one and two weeks' EAS of ST 36-GB34, the pain thresholds were significantly upregulated (P < 0.05), and the effect of EA2W was remarkably superior to that of EA2D and EA1W (P < 0.05). Correspondingly, CCI-induced decreased expression levels of Ras, c-Raf, ERK1 and p-ERK1/2 proteins, and p38 MAPK mRNA and p-p38MAPK protein in the hippocampus tissues were reversed by EA2W (P < 0.05). The above mentioned results indicated that EA2W induced cumulative analgesic effect may be closely associated with its function in removing neuropathic pain induced suppression of intracellular ERK and p38MAPK signaling in the hippocampus. PMID- 26161124 TI - Regulation of Neurotrophin-3 and Interleukin-1beta and Inhibition of Spinal Glial Activation Contribute to the Analgesic Effect of Electroacupuncture in Chronic Neuropathic Pain States of Rats. AB - Growing evidence indicates that neurotrophin-3, interleukin-1beta, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1beta in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL 1beta. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1beta production and spinal glial activity. PMID- 26161125 TI - Effect of Acupuncture on Functional Connectivity of Anterior Cingulate Cortex for Bell's Palsy Patients with Different Clinical Duration. AB - Acupuncture is widely used in the treatment of Bell's palsy (BP) in many countries, but its underlying physiological mechanism remained controversial. In order to explore the potential mechanism, changes of functional connectivity (FC) of anterior cingulate gyrus (ACC) were investigated. We collected 20 healthy (control group) participants and 28 BP patients with different clinical duration accepted resting state functional MRI (rfMRI) scans before and after acupuncture, respectively. The FC of ACC before and after acupuncture was compared with paired t-test and the detailed results are presented in the paper. Our results showed that effects of the acupuncture on FC were closely related to clinical duration in patients with BP, which suggested that brain response to acupuncture was closely connected with the status of brain functional connectivity and implied that acupuncture plays a homeostatic role in the BP treatment. PMID- 26161126 TI - Analysis and Thoughts about the Negative Results of International Clinical Trials on Acupuncture. AB - An increasing number of randomized controlled trials (RCTs) of acupuncture have proved the clinical benefits of acupuncture; however, there are some results that have shown negative results or placebo effects. The paper carried out an in-depth analysis on 33 RCTs in the 2011 SCI database, the quality of the reports was judged according to Jadad scores, and the "Necessary Information Included in Reporting Interventions in Clinical Trials of Acupuncture (STRICTA 2010)" was taken as the standard to analyze the rationality of the therapeutic principle. The difference between the methodology (Jadad) scores of the two types of research reports did not constitute statistical significance (P > 0.05). The studies with negative results or placebo effects showed the following deficiencies with respect to intervention details: (1) incompletely rational acupoint selection; (2) inconsistent ability of acupuncturists; (3) negligible needling response to needling; (4) acupuncture treatment frequency too low in most studies; and (5) irrational setting of placebo control. Thus, the primary basis for the negative results or placebo effects of international clinical trials on acupuncture is not in the quality of the methodology, but in noncompliance with the essential requirements proposed by acupuncture theory in terms of clinical manipulation details. PMID- 26161127 TI - Eye Acupuncture Treatment for Stroke: A Systematic Review and Meta-Analysis. AB - There were applications of eye acupuncture for stroke patients. Unfortunately, similar to many other Traditional Chinese Medicine (TCM) treatments, it lacks comprehensive evaluation and system review for its effect and safety. Objective. This study is a systematic review to appraise the safety and effectiveness of eye acupuncture for stroke. Methods. "Eye acupuncture therapy" in eleven databases was searched by randomized controlled trials and quasi-randomized controlled trials. The search activity was ended in April 2014. The data were extracted and assessed by three independent authors. Rev Man 5.0 software was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval. Results. Sixteen trials (1120 patients) were involved with generally poor methodological quality. The study indicated that when eye acupuncture was combined with western medicine compared to western medicine, there was a significant difference in the areas of mental state, swallow function, and NDS. When eye acupuncture was combined with western medicine and rehabilitation compared to western medicine and rehabilitation, there was significant difference in the changes of SSS, FMA, and constipation symptoms evaluation. No adverse events or side effects have been reported. Conclusions. The current evidence is insufficient and the rigorously designed trials are warranted. PMID- 26161129 TI - Adjustment for physical activity in studies of sedentary behaviour. AB - Sedentary behaviour (too much sitting, as distinct from too little exercise) has emerged as a potentially significant public health issue. Analytically, researchers have reported 'independent' associations between sedentary behaviour (SB) and a number of health outcomes by adjusting for physical activity (PA) (and other confounders), and conclude that SB is associated with the outcome even in those who are physically active. However, the logical rationale for why adjustments for PA are required is often not delineated, and as a consequence, PA has been conceptualised as a confounder, an intermediary, and an effect measure modifier-sometimes simultaneously-in studies of SB and health outcomes. This paper discusses the analytical assumptions underlying adjustment for PA in studies of SB and a given outcome, and considers the implications for associations between SB and health. PMID- 26161130 TI - Stimulation by Light and Sound: Therapeutics Effects in Humans. Systematic Review. AB - Introduction : The objective of the study was to make a systematic review of published studies that used the brain stimulation by light and sound as means to optimize brain function and increase the different treatments. Methods : The methods followed the Prisma model for eligibility of studies. Results : Four studies on the systematic review were included 3 experimental studies and 1 case report. Two of these studies were focused in learning and sportive performance, and 2 focused on increasing physical and mental health. Conclusion : It was concluded that the investigation of brain stimulation technique can be applied to induce favorable mental states to enlarge treatments of several disorders that affect humans in a safe and noninvasive way. It is suggested that positive results can also be found through the association of brain stimulation by light and sound with therapies that combat depression and anxiety states. PMID- 26161128 TI - The Effects of Mind-Body Interventions on Sleep Quality: A Systematic Review. AB - Study Objectives. To evaluate the effect of mind-body interventions (MBI) on sleep. Methods. We reviewed randomized controlled MBI trials on adults (through 2013) with at least one sleep outcome measure. We searched eleven electronic databases and excluded studies on interventions not considering mind-body medicine. Studies were categorized by type of MBI, whether sleep was primary or secondary outcome measure and outcome type. Results. 1323 abstracts were screened, and 112 papers were included. Overall, 67 (60%) of studies reported a beneficial effect on at least one sleep outcome measure. Of the most common interventions, 13/23 studies using meditation, 21/30 using movement MBI, and 14/25 using relaxation reported at least some improvements in sleep. There were clear risks of bias for many studies reviewed, especially when sleep was not the main focus. Conclusions. MBI should be considered as a treatment option for patients with sleep disturbance. The benefit of MBI needs to be better documented with objective outcomes as well as the mechanism of benefit elucidated. There is some evidence that MBI have a positive benefit on sleep quality. Since sleep has a direct impact on many other health outcomes, future MBI trials should consider including sleep outcome measurements. PMID- 26161131 TI - A New Approach for Mining Order-Preserving Submatrices Based on All Common Subsequences. AB - Order-preserving submatrices (OPSMs) have been applied in many fields, such as DNA microarray data analysis, automatic recommendation systems, and target marketing systems, as an important unsupervised learning model. Unfortunately, most existing methods are heuristic algorithms which are unable to reveal OPSMs entirely in NP-complete problem. In particular, deep OPSMs, corresponding to long patterns with few supporting sequences, incur explosive computational costs and are completely pruned by most popular methods. In this paper, we propose an exact method to discover all OPSMs based on frequent sequential pattern mining. First, an existing algorithm was adjusted to disclose all common subsequence (ACS) between every two row sequences, and therefore all deep OPSMs will not be missed. Then, an improved data structure for prefix tree was used to store and traverse ACS, and Apriori principle was employed to efficiently mine the frequent sequential pattern. Finally, experiments were implemented on gene and synthetic datasets. Results demonstrated the effectiveness and efficiency of this method. PMID- 26161132 TI - Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes. AB - Familial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations in MEFV and NLRP3 genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1beta. Overproduction of IL-1beta by Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations. PMID- 26161133 TI - Defining our destiny: trainee working group consensus statement on the future of emergency surgery training in the United Kingdom. AB - The United Kingdom National Health Service treats both elective and emergency patients and seeks to provide high quality care, free at the point of delivery. Equal numbers of emergency and elective general surgical procedures are performed, yet surgical training prioritisation and organisation of NHS institutions is predicated upon elective care. The increasing ratio of emergency general surgery consultant posts compared to traditional sub-specialities has yet to be addressed. How should the capability gap be bridged to equip motivated, skilled surgeons of the future to deliver a high standard of emergency surgical care? The aim was to address both training requirements for the acquisition of necessary emergency general surgery skills, and the formation of job plans for trainee and consultant posts to meet the current and future requirements of the NHS. Twenty nine trainees and a consultant emergency general surgeon convened as a Working Group at The Association of Surgeons in Training Conference, 2015, to generate a united consensus statement to the training requirement and delivery of emergency general surgery provision by future general surgeons. Unscheduled general surgical care provision, emergency general surgery, trauma competence, training to meet NHS requirements, consultant job planning and future training challenges arose as key themes. Recommendations have been made from these themes in light of published evidence. Careful workforce planning, education, training and fellowship opportunities will provide well-trained enthusiastic individuals to meet public and societal need. PMID- 26161134 TI - Chemistry and pharmacology of the herb pair Flos Lonicerae japonicae-Forsythiae fructus. AB - The Chinese medicine herb pair Flos Lonicerae japonicae (FLJ) and Forsythiae fructus (FF), is a representative heat-clearing (qing re) and detoxifying (jie du) combination that exhibits many pharmacological activities, including antibacterial, antiviral, antitumor, anti-inflammatory, and antioxidant effects. Extensive phytochemical studies have identified a series of bioactive compounds, such as chlorogenic acid from FLJ and forsythoside A from FF. This article provides a comprehensive review on the chemical and pharmacological principles of the traditional functions of FLJ-FF, and sheds light on further developments of this herb pair. PMID- 26161135 TI - Astragalus polysaccharide promotes the release of mature granulocytes through the L-selectin signaling pathway. AB - BACKGROUND: This study aims to investigate the leukogenic effect of astragalus polysaccharide (APS), to compare its effect of increasing the numbers of mature granulocytes with that of granulocyte colony-stimulating factor (G-CSF), and to investigate the mechanism. METHODS: Rats were arbitrarily grouped into four groups (control, cyclophosphamide (CTX), CTX + APS, and CTX + G-CSF groups), and each group was then arbitrarily divided into five subgroups according to the time period since CTX infusion (0, 4, 7, 10, and 14 days). The expression of leukocyte selectin (L-selectin), its ligand, and shedding-related protease on granulocytes was analyzed. Leukocyte counts were obtained. Chemotactic capacity of polymorphonuclear leukocytes (PMNLs) was assessed. RESULTS: Both APS and G-CSF restored the expression of L-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), CD11b/CD18, and ADAM17 to normal levels (P > 0.05 vs. control group on each time point), with APS eliciting a greater effect than G-CSF (P = 0.005 on day 7, P < 0.001 on day 10 and 14 for L-selectin; P = 0.038 on day 7, P = 0.001 on day 10, P < 0.001 on day 14 for PSGL-1; P < 0.001 on day 7, 10 and 14 for ADAM17; P < 0.001 on day 7, 10, and 14 for CD11b/CD18). The percentages of the bands and segmented bone marrow (BM) cells in myeloid neutrophils were higher in the CTX + APS group than in the CTX group on day 7 (P = 0.030) and reached normal levels on day 10 (P = 0.547) and 14 (P = 0.431) vs. control group. The ability of APS to increase numbers of PMNLs in peripheral blood after chemotherapy was significantly superior to that of G-CSF 7 days after chemotherapy (P = 0.029 on day 10, P = 0.006 on day 14). Moreover, APS more significantly improved the chemotactic ability of PMNLs among mature BM granulocytes and peripheral blood neutrophils after chemotherapy than did G-CSF (P < 0.001 on day 7, P = 0.001 on day 10 and P = 0.005 on day 14). CONCLUSIONS: APS promoted the differentiation and chemotactic ability of BM granulocytes via the L-selectin signaling pathway. PMID- 26161136 TI - Social Competence with an Unfamiliar Peer in Children and Adolescents with High Functioning Autism: Measurement and Individual Differences. AB - Children and adolescents with high functioning autism (HFA) display heterogeneity in social competence, which may be particularly evident during interactions with unfamiliar peers. The goal of this study was to examine predictors of social competence variability during an unfamiliar peer interaction. Thirty-nine participants with HFA and 39 age-, gender- and IQ-matched comparison participants were observed during dyadic laboratory interactions and detailed behavioral coding revealed three social competence dimensions: social initiative, social reciprocity, and social self-monitoring. Participants with HFA displayed higher social initiative but lower reciprocity than comparison participants. For participants with HFA, theory of mind was positively associated with observed initiative. For COM participants, social anxiety was negatively associated with reciprocity. However, for HFA participants, there was a quadratic relation between parent-reported social anxiety and observed reciprocity, demonstrating that low and high levels of anxiety were associated with low reciprocity. Results demonstrated the utility of our behavioral coding scheme as a valid assessment of social competence for children and adolescents with and without HFA. The curvilinear association between social anxiety and reciprocity highlights the importance of examining nonlinear relations in individuals with HFA, and emphasizes that discrete profiles of social anxiety in individuals with HFA may necessitate different treatment options. PMID- 26161138 TI - The development of the Content of Attenuated Positive Symptoms Codebook for those at clinical high risk of psychosis. AB - Examining the content of psychotic symptoms may be relevant for understanding symptom development particularly in those in the very early stages of psychosis. The Content of Attenuated Positive Symptoms codebook was developed as a means to overcome methodological issues in the current literature. Three separate samples at clinical high risk of psychosis were used to develop, modify and finalize the codebook. The inter-rater reliability was moderate to excellent. Specific content items were consistently endorsed across samples. This codebook offers a reliable way to assess content in the clinical high-risk population. PMID- 26161137 TI - Resilience in the Context of Chronic Stress and Health in Adults. AB - Over the past several decades, stress research has experienced a broadening of its pathologic focus to encompass the concept of resilience. There is a wealth of research on resilience but no general consensus regarding its conceptualization. Some define resilience as attaining eventual favorable outcomes following exposure to adversity. Others define it as specific relatively short-term responses characterized by a return to homeostasis after initial disruption due to a stressor, and still others refer to resilience as resources that enable the individual to withstand or recover from major stressors. Many of the existing conceptualizations of resilience are not applicable in the context of chronic stress which is particularly harmful to health. How do adults who experience chronic stress survive, manage, and thrive, and what resources enable them to do so? In this paper, we consider these questions by reviewing traditions of research and definitions of resilience in order to inform an understanding of resilience in general, and for the study of chronic stress in adults. Based on a review of the literature, we developed a taxonomy of resilience resources that can be applied broadly, and guide future research. PMID- 26161139 TI - Restricting lignin and enhancing sugar deposition in secondary cell walls enhances monomeric sugar release after low temperature ionic liquid pretreatment. AB - BACKGROUND: Lignocellulosic biomass has the potential to be a major source of renewable sugar for biofuel production. Before enzymatic hydrolysis, biomass must first undergo a pretreatment step in order to be more susceptible to saccharification and generate high yields of fermentable sugars. Lignin, a complex, interlinked, phenolic polymer, associates with secondary cell wall polysaccharides, rendering them less accessible to enzymatic hydrolysis. Herein, we describe the analysis of engineered Arabidopsis lines where lignin biosynthesis was repressed in fiber tissues but retained in the vessels, and polysaccharide deposition was enhanced in fiber cells with little to no apparent negative impact on growth phenotype. RESULTS: Engineered Arabidopsis plants were treated with the ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate 1-ethyl-3 methylimidazolium acetate ([C2C1im][OAc]) at 10 % wt biomass loading at either 70 degrees C for 5 h or 140 degrees C for 3 h. After pretreatment at 140 degrees C and subsequent saccharification, the relative peak sugar recovery of ~26.7 g sugar per 100 g biomass was not statistically different for the wild type than the peak recovery of ~25.8 g sugar per 100 g biomass for the engineered plants (84 versus 86 % glucose from the starting biomass). Reducing the pretreatment temperature to 70 degrees C for 5 h resulted in a significant reduction in the peak sugar recovery obtained from the wild type to 16.2 g sugar per 100 g biomass, whereas the engineered lines with reduced lignin content exhibit a higher peak sugar recovery of 27.3 g sugar per 100 g biomass and 79 % glucose recoveries. CONCLUSIONS: The engineered Arabidopsis lines generate high sugar yields after pretreatment at 70 degrees C for 5 h and subsequent saccharification, while the wild type exhibits a reduced sugar yield relative to those obtained after pretreatment at 140 degrees C. Our results demonstrate that employing cell wall engineering efforts to decrease the recalcitrance of lignocellulosic biomass has the potential to drastically reduce the energy required for effective pretreatment. PMID- 26161140 TI - Novel approach for the detection of tubular cell migration into the interstitium during renal fibrosis in rats. AB - BACKGROUND: The process of epithelial-mesenchymal transition (EMT), which is generally defined by phenotypic changes of injured tubules such as loss of epithelial markers or acquisition of mesenchymal markers, implies various activating steps, including proliferation, migration, and ability to produce extracellular matrix proteins. We established here a novel approach for the detection of tubular cell migration into the interstitium during renal fibrosis in vivo. RESULTS: Using an osmotic pump, bromodeoxyuridine (BrdU) was continuously given to 7-week-old Wistar rats for 4 weeks, and BrdU-positive cells were detected by immunostaining. BrdU-positive cells were present in aquaporin-1 positive proximal tubules, but not in the interstitium of BrdU-treated rat kidneys. After unilateral ureteral obstruction (UUO), some BrdU-positive tubular cells protruded from the basement membrane and migrated into the interstitium. Interstitial BrdU-positive cells were co-localized with alpha-smooth muscle actin, fibroblast specific protein-1, vimentin, and type I collagen, but not with CD68 or CD3. No BrdU-positive cells were observed in the interstitium of sham operated kidneys. The number of BrdU-positive cells migrating into the interstitium significantly increased and peaked at 8 days after UUO. CONCLUSIONS: Long-term BrdU labeling marked some of the proximal tubular cells and enabled us to detect tubular cell migration into the interstitium after UUO. This simple method might be useful to detect EMT in vivo. PMID- 26161141 TI - Efficacy of degarelix in prostate cancer patients following failure on luteinizing hormone-releasing hormone agonist treatment: results from an open label, multicentre, uncontrolled, phase II trial (CS27). AB - OBJECTIVE: To evaluate the efficacy of second-line degarelix in patients with prostate cancer (PCa) after treatment failure with a luteinizing hormone releasing hormone (LHRH) agonist. METHODS: This 1-year exploratory, multicentre, open-label phase II trial was performed in 2 patient cohorts (Cohort 1, n = 25; Cohort 2, n = 12) in Germany. Patients with castrate-resistant PCa after primary hormonal treatment received degarelix 240 mg, followed by 11 monthly maintenance doses of 80 mg. The primary endpoint was the proportion of patients with decreasing/stable prostate-specific antigen (PSA) (relative change ?+10% of baseline PSA) after 3 months. RESULTS: At Month 3, the response rate (intention to-treat, last observation carried forward analysis) was 16.7% [95% confidence interval (CI): 4.74-37.38] in Cohort 1 and 33.3% (95% CI: 9.92-65.11) in Cohort 2. The probability of completing 12 months without PSA progression was 8.8% (95% CI: 1.51-24.3) in Cohort 1 and 8.3% (95% CI: 0.5-31.1) in Cohort 2. Degarelix was well tolerated; the most frequently reported adverse events were local injection site reactions. CONCLUSIONS: In PCa patients who failed LHRH therapy, degarelix was well tolerated and achieved a limited PSA response. Phase III trials show that disease control benefits with degarelix versus agonists are more clearly demonstrated as first-line therapy. PMID- 26161142 TI - A prospective, observational grouped analysis to evaluate the effect of triptorelin on lower urinary tract symptoms in patients with advanced prostate cancer. AB - OBJECTIVES: Few studies have assessed the effect of gonadotropin-releasing hormone (GnRH) agonists, such as triptorelin, on lower urinary tract symptoms (LUTS) in patients with advanced prostate cancer. Therefore, multiple, national observational, noninterventional studies were initiated to assess the effectiveness of triptorelin in reducing moderate or severe LUTS [International Prostate Symptom Score (IPSS) >7] in men with prostate cancer starting triptorelin therapy in clinical practice. METHODS: Prospective, noninterventional, multicentre studies of LUTS located in Algeria, Belgium, China, Hungary, Romania and South Korea, in patients who were scheduled to receive triptorelin (3-month extended release or 1-month formulation) in clinical practice. The primary effectiveness endpoint was the proportion of patients with moderate or severe LUTS after 48 weeks as assessed by IPSS. Secondary endpoints included the distribution of IPSS categories, total IPSS and prostate-specific antigen (PSA) levels at baseline, 24 and 48 weeks. RESULTS: In total, 2461 patients were recruited in the studies; 1282 patients had moderate or severe LUTS at baseline (IPSS > 7), received triptorelin and had follow-up IPSS. Mean total IPSS was reduced from 18.2 [95% confidence interval (CI) 17.8-18.5] at baseline to 11.9 (95% CI 11.5-12.3; p < 0.001) and 10.6 (95% CI 10.2-11.0; p < 0.001) at weeks 24 and 48, respectively. Mean PSA levels were reduced from 117.9 ng/ml (95% CI 93.8-141.9) at baseline to 8.5 ng/ml (95% CI 5.2-11.7) and 16.6 ng/ml (95% CI 7.4-25.8) at weeks 24 and 48, respectively. There was a significant correlation between total IPSS change from baseline and PSA change from baseline at weeks 24 and 48 (rho = 0.3 and 0.2, p < 0.001). CONCLUSIONS: The improvement in LUTS in men with locally advanced or metastatic prostate cancer after 24-48 weeks suggests that triptorelin is effective in improving LUTS in this subgroup of patients. PMID- 26161143 TI - Efficacy of triptorelin pamoate 11.25 mg administered subcutaneously for achieving medical castration levels of testosterone in patients with locally advanced or metastatic prostate cancer. AB - OBJECTIVES: Gonadotropin-releasing hormone agonists are widely used as androgen deprivation therapy in many men with locally advanced or metastatic prostate cancer. Gonadotropin-releasing hormone agonists are delivered by intramuscular injection every 1, 3 or 6 months, but in some patients subcutaneous injection may be more appropriate. This study assessed the efficacy and safety profile of the gonadotropin-releasing hormone agonist, triptorelin pamoate, when administered by the subcutaneous route. METHODS: In this multicentre, open-label, single-arm study, androgen deprivation therapy-naive men with locally advanced or metastatic prostate cancer received the gonadotropin-releasing hormone agonist triptorelin pamoate 11.25 mg (3-month formulation) by the subcutaneous route twice (at baseline and 13 weeks later). The co-primary efficacy endpoints were the proportion of patients with a castration level of serum testosterone (<50 ng/dl) after 4 weeks, and of these, those still castrated after 26 weeks. RESULTS: Of the 126 treated patients, 123 [97.6%; 95% confidence interval (CI): 93.2-99.5)] were castrated 4 weeks after the first subcutaneous injection, and 115/119 patients (96.6%; 95% CI: 91.6-99.1) castrated at 4 weeks maintained castration at 26 weeks. Median prostate-specific antigen levels were reduced by 64.2 and 96.0% at 4 and 26 weeks, respectively. The probability of maintaining a testosterone level <20 ng/dl up to 26 weeks was 90.0% (95% CI: 85.0-95.0). The most frequently occurring treatment-related adverse events were typical of gonadotropin-releasing hormone agonist treatment (hot flushes, increased weight, erectile dysfunction and hyperhidrosis). CONCLUSIONS: This study demonstrates that triptorelin pamoate 11.25 mg administered by the subcutaneous route every 3 months is as efficacious and well tolerated as administration via the intramuscular route in men with locally advanced or metastatic prostate cancer. PMID- 26161145 TI - Tadalafil therapy for erectile dysfunction following prostatectomy. AB - Erectile dysfunction is a major complication affecting the quality of life of patients and partners after radical prostatectomy. Evolving evidence suggests that early penile rehabilitation may provide better erectile function after surgery. Phosphodiesterase type 5 (PDE-5) inhibitors are routinely considered a first-line treatment option in most algorithms for penile rehabilitation owing to their efficacy, ease of use, wide availability and minimal morbidity. Tadalafil is a long-acting, potent PDE-5 inhibitor for erectile dysfunction, with demonstrated effect in animal studies at preserving penile smooth muscle content and prevention of fibrosis of cavernosal tissue. This article evaluates the existing literature on tadalafil and critically analyzes its impact on erectile function following radical prostatectomy. PMID- 26161144 TI - The role of radiation therapy in the treatment of metastatic castrate-resistant prostate cancer. AB - In the setting of castrate-resistant prostate cancer, patients present with a variety of symptoms, including bone metastases, spinal cord compression and advanced pelvic disease. Fortunately, a variety of radiotherapeutic options exist for palliation. This article focuses on these options, including both external beam radiotherapy and radiopharmaceuticals. PMID- 26161146 TI - Clinical experience with temsirolimus in the treatment of advanced renal cell carcinoma. AB - Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR) kinase, a protein that has been shown to be particularly active in metastatic renal cell carcinoma (mRCC) with poor prognosis. Therefore, temsirolimus should be considered as the first-line treatment indicated in mRCC patients classified as poor risk. The benefits of temsirolimus are not limited to an increased survival but are also related to a better quality of life, which is certainly one of the most important aspects in the clinical management of these frail patients. Temsirolimus is a well-tolerated treatment, and the most frequent adverse events are manageable with supportive care. To this end, the identification of predictive factors of response to temsirolimus could help us to better select patients and obtain a more tailored clinical management of mRCC. PMID- 26161147 TI - The reliability of non-invasive biophysical outcome measures for evaluating normal and hyperkeratotic foot skin. AB - BACKGROUND: Hyperkeratosis of foot skin is a common skin problem affecting people of different ages. The clinical presentation of this condition can range from dry flaky skin, which can lead to fissures, to hard callused skin which is often painful and debilitating. The purpose of this study was to test the reliability of certain non-invasive skin measurement devices on foot skin in normal and hyperkeratotic states, with a view to confirming their use as quantitative outcome measures in future clinical trials. METHODS: Twelve healthy adult participants with a range of foot skin conditions (xerotic skin, heel fissures and plantar calluses) were recruited to the study. Measurements of normal and hyperkeratotic skin sites were taken using the following devices: Corneometer(r) CM 825, Cutometer(r) 580 MPA, Reviscometer(r) RVM 600, Visioline(r) VL 650 Quantiride(r) and Visioscan(r) VC 98, by two investigators on two consecutive days. The intra and inter rater reliability and standard error of measurement for each device was calculated. RESULTS: The data revealed the majority of the devices to be reliable measurement tools for normal and hyperkeratotic foot skin (ICC values > 0.6). The surface evaluation parameters for skin: SEsc and SEsm have greater reliability compared to the SEr measure. The Cutometer(r) is sensitive to soft tissue movement within the probe, therefore measurement of plantar soft tissue areas should be approached with caution. Reviscometer(r) measures on callused skin demonstrated an unusually high degree of error. CONCLUSIONS: These results confirm the intra and inter rater reliability of the Corneometer(r), Cutometer(r), Visioline(r) and Visioscan(r) in quantifying specific foot skin biophysical properties. PMID- 26161148 TI - Unraveling the potential co-contributions of cerebral small vessel vasculopathy to the pathogenesis of Alzheimer's dementia. AB - Emerging evidence for the potential co-contributions of small vessel vasculopathy to dementia has resulted in a more nuanced view of Alzheimer's disease (AD) pathogenesis. Although cerebral small vessel disease, visualized on magnetic resonance imaging as hyperintense signal abnormalities, independently predicts the incidence and clinical progression of dementia, the relationships between AD pathology, white matter hyperintensity volume, genotype, and cognitive decline in AD remain unclear. The study by Morgen and colleagues, recently published in Alzheimer's Research & Therapy, presents important new findings on the associations between apolipoprotien E epsilon4 genotype, white matter hyperintensities, and cognition, independent of vascular risk, in a cohort of AD patients. PMID- 26161149 TI - Vitamin D receptor gene polymorphisms and musculoskeletal injuries in professional football players. AB - The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphisms and musculoskeletal injury (MI) in elite football players. In total, 54 male professional football players were recruited from an official Italian professional championship team between 2009 and 2013. The cohort was genotyped for the ApaI, BsmI and FokI polymorphisms and MI data were collected over four football seasons. No significant differences were identified among the genotypes in the incidence rates or severity of MI (P=0.254). In addition, no significant associations were observed between VDR polymorphisms and MI phenotypes (P=0.460). However, the results of the casewise multiple regression analysis indicated that the ApaI genotypes accounted for 18% of injury severity (P=0.002). Therefore, while the BsmI and FokI polymorphisms did not appear to be associated with the severity or incidence of MI, the ApaI genotypes may have influenced the severity of muscle injury in top-level football players. PMID- 26161150 TI - Enamel matrix proteins exhibit growth factor activity: A review of evidence at the cellular and molecular levels. AB - Enamel matrix derivative (EMD) is a commercially available protein extract, mainly comprising amelogenins. A number of other polypeptides have been identified in EMD, mostly growth factors, which promote cementogenesis and osteogenesis during the regeneration processes through the regulation of cell proliferation, differentiation and activity; however, not all of their functions are clear. Enamel extracts have been proposed to have numerous activities such as bone morphogenetic protein- and transforming growth factor beta (TGF-beta)-like activity, and activities similar to those of insulin-like growth factor, fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor and epidermal growth factor. These activities have been observed at the molecular and cellular levels and in numerous animal models. Furthermore, it has been suggested that EMD contains an unidentified biologically active factor that acts in combination with TGF-beta1, and several studies have reported functional similarities between growth factors and TGF-beta in cellular processes. The effects of enamel extracts on the cell cycle and biology are summarized and discussed in this review. PMID- 26161153 TI - Pre-induced Lac Operon Effect on Non Specific Sugars: Pre-culture Effect is Dependent on Strength of Induction, Exponential Phase and Substrate Concentration. AB - The source and history of the cell plays an important role in influencing the phenotypic properties of the organism in a particular environmental condition. Pre-induced lac operon provides benefit on lactose environment. During metabolism lactose is broken down into glucose and galactose. The fate of cells with pre induced lac operon on glucose and galactose milieu is not known. The influence of nutritional status of the medium, level of pre-induction and growth phase on pre culture effect is not investigated. Effect of pre-induced lac operon on non specific sugars along with the factors that influence this effect was enumerated in the present study. Results of this present study indicate that pre-induced lac operon provide benefit in terms of growth on galactose milieu. This study also suggests that Pre induced lac operon effect depends on the (i) strength of induction in the pre-culture, (ii) nutritional content of the environment and (iii) exponential growth phase of the organism. The above study will help in the better characterization of the pre culture effect. It will also help in the better understanding of the relation between gene expression and growth physiology. PMID- 26161151 TI - DNA vaccination for prostate cancer: key concepts and considerations. AB - While locally confined prostate cancer is associated with a low five year mortality rate, advanced or metastatic disease remains a major challenge for healthcare professionals to treat and is usually terminal. As such, there is a need for the development of new, efficacious therapies for prostate cancer. Immunotherapy represents a promising approach where the host's immune system is harnessed to mount an anti-tumour effect, and the licensing of the first prostate cancer specific immunotherapy in 2010 has opened the door for other immunotherapies to gain regulatory approval. Among these strategies DNA vaccines are an attractive option in terms of their ability to elicit a highly specific, potent and wide-sweeping immune response. Several DNA vaccines have been tested for prostate cancer and while they have demonstrated a good safety profile they have faced problems with low efficacy and immunogenicity compared to other immunotherapeutic approaches. This review focuses on the positive aspects of DNA vaccines for prostate cancer that have been assessed in preclinical and clinical trials thus far and examines the key considerations that must be employed to improve the efficacy and immunogenicity of these vaccines. PMID- 26161154 TI - Spread of Enterococcal Surface Protein in Antibiotic Resistant Entero-coccus faecium and Enterococcus faecalis isolates from Urinary Tract Infections. AB - Enterococci rank among leading cause of nosocomial bacteremia and urinary tract infection in hospital and community acquired infections. Several traits that may contribute to enhanced virulence have been identified in Enterococci. Extracellular surface protein (Esp) is a virulence factor that contributes in biofilm formation and resistance to environmental stresses. In this study we aimed to determine occurrence of esp in E. faecium and E. faecalis isolates isolated from urinary tract infections and to investigate whether there is any correlation between presence of esp and antibiotic resistance. One hundred and sixty six isolates were collected from patients with UTI and after identification by biochemical and PCR, antibiotic resistances were examined. The presence of esp was investigated by primer-specific PCR. 43.3% of isolates identified as E. faecium and 56.7% as E. faecalis. The esp gene was found in 76.1% of E. faecium isolates and 77.9% of E. faecalis isolate. There were significant correlation between esp positive E. faecium and resistance to Vancomycin (p<0.01), also in E.faecalis we found correlation between esp positive and resistance to Ampicillin, Chloramphenicol and Tetracycline (p<0.01, p<0.01, p<0.01 respectively). Occurrence of esp in our isolates from urinary tract infection was high that indicates importance of this gene in urinary tract infections and shows importance of ability to forming biofilm and hydrophobicity of surface of Enterococci for causing urinary infection by Enterococci. Also, our finding showed significant correlation between resistance to antibiotics and presence of esp in Enterococci. PMID- 26161155 TI - A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide. AB - Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patients who have progression of disease or who are unable to tolerate the side effect profile of more standard systemic therapy. Larger longitudinal studies or case series are needed to confirm and further investigate infliximab's role in localized scleroderma. PMID- 26161152 TI - Epigenetic activities of flavonoids in the prevention and treatment of cancer. AB - Aberrant epigenetic modifications are described in an increasing number of pathological conditions, including neurodegenerative diseases, cardiovascular diseases, diabetes mellitus type 2, obesity and cancer. The general reversibility of epigenetic changes makes them an attractive and promising target e.g. in the treatment of cancer. Thus, a growing number of epigenetically active compounds are currently tested in clinical trials for their therapeutic potential. Interestingly, many phytochemicals present in plant foods, particularly flavonoids, are suggested to be able to alter epigenetic cellular mechanisms. Flavonoids are natural phenol compounds that form a large group of secondary plant metabolites with interesting biological activities. They can be categorized into six major subclasses, which display diverse properties affecting the two best characterized epigenetic mechanisms: modulation of the DNA methylation status and histone acetylation. High dietary flavonoid intake has strongly been suggested to reduce the risk of numerous cancer entities in a large body of epidemiological studies. Established health-promoting effects of diets rich in fruit and vegetables are faced by efforts to use purified flavonoids as supplements or pharmaceuticals, whereupon data on the latter applications remain controversial. The purpose of this review is to give an overview of current research on flavonoids to further elucidate their potential in cancer prevention and therapy, thereby focusing on their distinct epigenetic activities. PMID- 26161156 TI - Clinical Characteristics and Outcome of Primary Sjogren's Syndrome: A Large Asian Indian Cohort. AB - OBJECTIVE: To characterise the clinical features, immunological profile and outcome in a cohort of Asian Indian patients with primary Sjogren's syndrome (SS). METHODS: Electronic medical records from a tertiary care teaching hospital in south India were screened for SS between 2004 and 2011. Patients fulfilling American European Consensus group (AECG) 2002 or American College of Rheumatology (ACR) 2012 classification criteria were included. Agglomerative hierarchical cluster analysis to identify patterns of associations between clinical and immunological features was done. Multivariate logistic regression to identify predictors of major systemic involvement was performed. Data on treatment and outcome were retrieved from electronic records. RESULTS: Of 423 patients suspected to have SS, 332 fulfilled inclusion criteria. Only 8.3% of patients complained of sicca symptoms on their own at initial presentation. Younger age of onset, higher female to male ratio, paucity of cryoglobulinemia, Raynaud's phenomenon and hyperglobulinemia were unique to this cohort. Cluster analysis revealed two subsets: The first cluster comprised of patients having a major systemic illness with high antibody titers and the second comprised of seronegative patients with mild disease. Over a third of SS cases had severe systemic manifestations necessitating treatment with immunosuppressants. In multivariate logistic regression analysis, anti-Ro and anti-La antibody positivity was associated with higher odds for systemic disease features (OR=2.67, P=0.03 and OR=3.25, P=0.003, respectively) whereas chronic pain was associated with lower odds (OR=0.4, p=0.032). Clinical improvement including symptomatic benefit in sicca and musculoskeletal features was noted with immunomodulators in the majority. CONCLUSION: Our cohort of patients with SS has characteristic clinical features; some of them are in contrast with previous observations reported in European patients. This cohort consisted of two distinct patient clusters. The first cluster was associated with major systemic illness and high antibody titers, where as the second cluster comprised of seronegative patients with mild disease. Association of antibody positivity with systemic features was further confirmed on logistic regression analysis. PMID- 26161157 TI - Medial Patellofemoral Ligament Reconstruction: A Longitudinal Study Comparison of 2 Techniques with 2 and 5-Years Follow-Up. AB - BACKGROUND: The purpose of this study was to compare the results of two popular surgical techniques for medial patellofemoral ligament MPFL reconstruction with a minimum of two-year follow-up. METHODS: Fifty-eight patients with traumatic tear of the medial patellofemoral ligament were included in one of the two surgical groups. Group 1 MPFLs were reconstructed through graft endobutton fixation and Group 2 through graft anchor fixation into the patella. After two to five-year follow-up, patients were asked to answer knee function questionnaires (Fulkerson and Kujala) as well as the SF-36 life quality score. RESULTS: There were no statistical difference among postoperative Kujala, Fulkerson, and SF-36 questionnaires scores between Groups 1 and 2. There were statistical significant differences favorable to patients in Group 1 with a shorter follow-up length (2-5 years) compared to those with a longer period of 5-10 years for both Kujala and Fulkerson scores and no difference for group 2. CONCLUSION: Both medial patellofemoral ligament reconstruction techniques had similar results in a two to ten-year follow-up according to functions and life quality questionnaires. Furthermore, endobutton fixation for the patellar edge of the graft had better results in patients with 2 years of follow-up than those with 5 years. Gender was not significant for surgical results. Moreover, group 1 patients had higher number of complications. PMID- 26161158 TI - The Prevalence and Severity of Joint Problems and Disability in Patients with Poliomyelitis in Urban India. AB - Poliomyelitis is caused by an enterovirus infection of the anterior horn cells in the spinal cord. Up to 40% of survivors recover full muscle strength, however 60 90% are left with varying degrees of residual paralysis, where the patient suffers from cramping myalgia and lower motor neuron pattern weakness. This study aimed to identify and quantify, in terms of prevalence and severity of the types of joint deformities encountered in polio sufferers. It also aimed to assess the disability caused by such problems. Finally we documented the provision and use of mobility aids, orthotics and surgery in the patient group. Impairment was confined to one lower limb, and this is consistent, as the majority of patients were infected in infancy. The study found that pes cavus, scoliosis, flexion deformity of the knee and true lower-limb shortening accounted for over half of the deformities found. The mean Barthel Disability score was 19 and over 80% of patients used at least one aid, usually in the form of a Knee-Ankle-Foot Orthosis (KAFO). Surgery also plays a large in role in the management of polio patients, however necessity needs to be assessed on an individual basis taking into account many aspects of the patient's life. PMID- 26161159 TI - A Novel Surgical Technique for Removing Buried Cannulated Screws Using a Guidewire and Countersink: A Report of Two Cases. AB - Removal of metal implants is a common procedure that is performed for a variety of indications. However, problems such as a buried screw head may occasionally arise and render hardware removal difficult or even impossible. The problem is further compounded when the initial screw was inserted percutaneously or via a minimally-invasive (MIS) technique. In the present paper, we introduce a novel, minimally invasive technique to remove buried cannulated screws which obviates the need for excessive extension of the skin incision, surgical exploration, soft tissue dissection or excess bone removal, which surgeons may otherwise have to undertake to uncover the buried screw head. This technique is especially useful in removing cannulated screws which have been inserted using small stab incisions and MIS techniques initially. This technique can be applied to the removal of buried cannulated screws which are placed into any bone in the body. PMID- 26161160 TI - Superficial Peroneal Nerve Incarceration in the Fibular Fracture Site of a Pronation External Rotation Type Ankle Fracture. AB - Ankle fractures are common representing up to 10% of all fractures with an incidence that is rising. Both conservative treatment and operative management of ankle fractures can lead to excellent outcomes. Neurovascular injuries are uncommon but can be a source of significant morbidity and associated poor outcome. The superficial peroneal nerve (SPN) in the lateral approach and the sural nerve in the posterolateral approach are at risk of injury. We report an unexpected finding of a superficial peroneal nerve incarcerated in the fibular fracture site of pronation external rotation type/ Weber-C ankle fracture. To the best of our knowledge we believe this to be the first English language report of an incarcerated SPN at a fibular ankle fracture site. PMID- 26161161 TI - Hybrid Biosynthetic Autograft Extender for Use in Posterior Lumbar Interbody Fusion: Safety and Clinical Effectiveness. AB - Autologous iliac crest bone graft is the preferred option for spinal fusion, but the morbidity associated with bone harvest and the need for graft augmentation in more demanding cases necessitates combining local bone with bone substitutes. The purpose of this study was to document the clinical effectiveness and safety of a novel hybrid biosynthetic scaffold material consisting of poly(D,L-lactide-co glycolide) (PLGA, 75:25) combined by lyophilization with unmodified high molecular weight hyaluronic acid (10-12% wt:wt) as an extender for a broad range of spinal fusion procedures. We retrospectively evaluated all patients undergoing single- and multi-level posterior lumbar interbody fusion at an academic medical center over a 3-year period. A total of 108 patients underwent 109 procedures (245 individual vertebral levels). Patient-related outcomes included pain measured on a Visual Analog Scale. Radiographic outcomes were assessed at 6 weeks, 3-6 months, and 1 year postoperatively. Radiographic fusion or progression of fusion was documented in 221 of 236 index levels (93.6%) at a mean (+/-SD) time to fusion of 10.2+4.1 months. Single and multi-level fusions were not associated with significantly different success rates. Mean pain scores (+SD) for all patients improved from 6.8+2.5 at baseline to 3.6+2.9 at approximately 12 months. Improvements in VAS were greatest in patients undergoing one- or two level fusion, with patients undergoing multi-level fusion demonstrating lesser but still statistically significant improvements. Overall, stable fusion was observed in 64.8% of vertebral levels; partial fusion was demonstrated in 28.8% of vertebral levels. Only 15 of 236 levels (6.4%) were non-fused at final follow up. PMID- 26161162 TI - The Effect of Low Molecular Weight Heparins on Fracture Healing. AB - Venous Thromboembolism is a serious complication in the trauma patient. The most commonly studied and used anticoagulant treatment in prophylaxis of thrombosis is heparin. The prolonged use of unfractionated heparin has been connected with increased incidence of osteoporotic fractures. Low molecular-weight-heparins (LMWHs) have been the golden rule in antithrombotic therapy during the previous two decades as a way to overcome the major drawbacks of unfractioned heparin. However there are few studies reporting the effects of LMWHs on bone repair after fractures. This review presents the studies about the effects of LMWHs on bone biology (bone cells and bone metabolism) and underlying the mechanisms by which LMWHs may impair fracture healing process. The authors' research based on literature concluded that there are no facts and statistics for the role of LMWHs on fracture healing process in humans and the main body of evidence of their role comes from in vitro and animal studies. Further large clinical studies designed to compare different types of LMWHs, in different dosages and in different patient or animal models are needed for exploring the effects of LMWHs on fracture healing process. PMID- 26161164 TI - Diagnostic single nucleotide polymorphism markers to identify hybridization between dromedary and Bactrian camels. AB - The technique to produce hybrid Tulu or Nar camels from crosses between dromedary and Bactrian camels is common throughout Middle Eastern and Central Asian countries. Formerly, these hybrids were highly valued as strong and persistent pack animals but today are bred to improve milk or wool quality in the respective species and for camel wrestling. We developed a diagnostic single nucleotide polymorphism (SNP) panel to identify cryptic ancestry in F1 hybrids and their backcrosses by selecting loci from whole genome data, which were fixed for different alleles in either dromedary or domestic and wild Bactrian camel. With this SNP panel we are able to identify the hybridization patterns in camels with uncertain origins, support hybrid breeding management and to detect potential rare dromedary introgression in the last wild Bactrian camels in Mongolia and China. PMID- 26161163 TI - Ocular Surface as Barrier of Innate Immunity. AB - Sight is one of the most important senses that human beings possess. The ocular system is a complex structure equipped with mechanisms that prevent or limit damage caused by physical, chemical, infectious and environmental factors. These mechanisms include a series of anatomical, cellular and humoral factors that have been a matter of study. The cornea is not only the most powerful and important lens of the optical system, but also, it has been involved in many other physiological and pathological processes apart from its refractive nature; the morphological and histological properties of the cornea have been thoroughly studied for the last fifty years; drawing attention in its molecular characteristics of immune response. This paper will review the anatomical and physiological aspects of the cornea, conjunctiva and lacrimal apparatus, as well as the innate immunity at the ocular surface. PMID- 26161165 TI - Perspectives of Puerto Rican Adults about Heart Health and a Potential Community Program. AB - BACKGROUND: Puerto Ricans are the second largest Hispanic group in the U.S. and older adults have significant health disparities. Educational programs that address heart disease risk for this population have rarely been developed and implemented. PURPOSE: To address this gap, the Heart Healthy Initiative for Puerto Rican adults is being developed. To develop it as a participatory program, the community members were asked about their perspectives. METHODS: Five focus groups with 28 participants, aged 45-60, were conducted, transcribed and analyzed using Thematic Analysis. In-depth analysis of meanings of health promoting behaviors, in the context of cultural beliefs and values was carried out. RESULTS: The following themes were identified: Health as balance and integration; Health as connection of self, connection with others; Cultural meanings of lifestyle choices; Stresses and struggles. Participants suggested that the program should have significant variety and a holistic perspective, be sensitive to different needs and motivations, stimulate mutual understanding and shared cultural meanings. DISCUSSION: The program needs to support lifestyle changes which maximally preserve traditions and to introduce multi-level changes. TRANSLATION TO HEALTH EDUCATION PRACTICE: The identified cultural meanings of diet, physical activity and relationships were taken into account to develop the educational curriculum. PMID- 26161166 TI - [Analysis of the management of the newborn under the national subsidy strategy of births and obstetric and neonatal emergency care at Pediatric University Hospital Charles de Gaulle, Ouagadougou (Burkina Faso)]. PMID- 26161168 TI - [Neurogenic osteoarthritis in Guillain Barre syndrome: a rare complication (case report and review of the literature)]. PMID- 26161167 TI - Body composition in children with juvenile idiopathic arthritis: effect of dietary intake of macronutrient: results from a cross sectional study. AB - INTRODUCTION: The aim of this study was to evaluate the relationship between macronutrient intake, body composition (lean body mass and fat mass) and bone mineral content in Moroccan children with juvenile idiopathic arthritis (JIA). METHODS: A cross-sectional study, conducted between May 2010 and June 2011, covering out patient with JIA. The characteristics of patients were collected. The nutritional status was assessed by a food questionnaire including data of food intake during 7 consecutive days using 24-hour dietary recall. Food intake was quantified using the software Bilnut (Bilnut version 2.01, 1991). Dietary intake of macronutrients was expressed as percentage contribution to total energy. Body composition was evaluated with DXA total-body measurements (bone mineral content BMC expressed in g, lean body mass LBM and fat mass FM expressed in kg). RESULTS: 33 patients were included. The mean age was 10.4 +/- 4.3 years. The median disease duration was 2 (1-4.5) years. The median of LBM, FM and BMC were 19 kg (13.82-33.14), 5 kg (3.38-9.14) and 1044.90 g (630.40-1808.90) respectively. We found a positive correlation between LBM and dietary intake of carbohydrate (r= 0.4; p = 0.03). There were no significant association between LBM and intake of lipids, or protein. Moreover, no association was found between FM, BMC and intake of carbohydrates, lipids and proteins. CONCLUSION: This study suggests that there is a positive correlation between carbohydrates intake and LBM; however, dietary intake does not influence FM and BMC. Prospective studies with larger numbers of patients appear to be needed to confirm our findings. PMID- 26161169 TI - [Study of low birth weight associated with maternal age and parity in a population of mother and children in Lubumbashi]. PMID- 26161170 TI - Risk factors for unsuccessful tuberculosis treatment outcome (failure, default and death) in public health institutions, Eastern Ethiopia. AB - INTRODUCTION: Unsuccessful TB treatment outcome is a serious public health concern. It is compelling to identify, and deal with factors determining unsuccessful treatment outcome. Therefore, study was aimed to determine pattern of unsuccessful TB treatment outcome and associated factors in eastern Ethiopia. METHODS: A case control study was used. Cases were records of TB patients registered as defaulter, dead and/or treatment failure where as controls were those cured or treatment complete. Multivariate logistic regression models were used to derive adjusted odds ratios (OR) at 95% CI to examine the relationship between the unsuccessful TB treatment outcome and patients' characteristics. RESULTS: A total of 990 sample size (330 cases and 660 controls) were included. Among cases (n = 330), majority 212(64.2%) were because of death, 100(30.3%) defaulters and 18(5.5%) were treatment failure. Lack of contact person(OR = 1.37; 95% CI 1.14-2.9, P, .024), sputum smear negative treatment category at initiation of treatment (OR = 1.8; 95% CI 1.3-5.5,P, .028), smear positive sputum test result at 2(nd) month after initiation treatment (OR = 14; 95% CI 5.5-36, P,0.001) and HIV positive status (OR = 2.5; 95% CI 1.34-5.7, P, 0.01) were independently associated with increased risk of unsuccessful TB treatment outcome. CONCLUSION: Death was the major cause of unsuccessful TB treatment outcome. TB patients do not have contact person, sputum smear negative treatment category at initiation of treatment, smear positive on 2(nd) month after treatment initiation and HIV positive were factors significantly associated unsuccessful treatment outcome. TB patients with sputum smear negative treatment category, HIV positive and smear positive on 2(nd) nd month of treatment initiation need strict follow up throughout DOTs period. PMID- 26161171 TI - [Horton disease revealed by dyspnea]. PMID- 26161172 TI - [Postpartum acute coronary syndrome secondary to spontaneous coronary dissection: report of a case]. PMID- 26161173 TI - [Angioid streaks and elastic pseudoxanthoma]. PMID- 26161174 TI - Prevalence of persistent microalbuminuria and associated factors among HIV infected children attending a Tertiary Hospital in Northern Tanzania: a cross sectional, analytical study. AB - INTRODUCTION: Human Immunodeficiency Virus (HIV) infection is a significant cause of paediatric morbidity and mortality especially in Sub-Saharan Africa. It affects the kidney by injuring the glomerular and tubular epithelial cells causing leakage of albumin in urine. Microalbuminuria is known to be an early indicator of kidney injury including HIVAN. The purpose of this study was to identify the prevalence and factors associated with microalbuminuria among HIV infected children receiving care and treatment at Kilimanjaro Christian Medical Centre (KCMC). METHODS: We conducted a cross sectional hospital based analytical study at KCMC from December 2012 to April 2013. It involved children who are HIV infected attending child centred family care clinics (CCFCC). Patients' demographic and clinical characteristics were extracted from the file; physical examination performed. Urine samples were analysed for by HemoCue Albumin 201 system analyzer. Statistical package for social sciences (SPSS) version 16.0 was be used to process and analyze the data. RESULTS: Three hundred thirty HIV infected children under 18 years were recruited during the study period. Mean age was 119.4 (5-218) months. Prevalence of microalbuminuria by using HemoCue Albumin 201 analyzer was 28.8% (n = 95). Presence of microalbuminuria was significantly associated with severity of HIV disease progression according to WHO disease stage (p = 0.0015) and CD4 count less than 350 cells/uL (p = 0.044). CONCLUSION: The study has shown that microalbuminuria is common in HIV infected children. Early screening and treatment of microalbuminuria is important to minimize the risk of developing end stage kidney disease. Children with advanced HIV disease and those with CD4 count less than 350 cells/uL should be given priority for urinary albumin screening in a setting without routine screening for microalbuminuria. PMID- 26161175 TI - Socio-demographic factors associated with underweight and stunting among adolescents in Ethiopia. AB - INTRODUCTION: Nutrition during adolescence plays an important role in the individual's life. There are different factors that affect nutritional status of adolescents. Socio Economic Status, age, sex and mothers' educational level are among the important determinants factors of nutritional status of adolescents. Younger adolescents tend to be more undernourished than older adolescents, and, contrary to expectations that boys are almost twice as undernourished as girls. In this study, we test the competing hypothesis about the correlates of nutritional status among Ethiopian adolescents. METHODS: We report a total of 2084 adolescents from the second round of a 5-year longitudinal study in Jimma zone, southwest Ethiopia. Univariate and Multivariable linear regression were used to assess socio-demographic factors associated with Underweight and Stunting among Adolescents in Jimma zone. RESULTS: Age, highest grade completed, job and last attended in community school were positively associated with BMI for Age z score and highest grade completed, household income and job were positively associated with Height for Age z-score. However, male gender was negatively associated with BMI for Age z-score and male gender, last attended in community school, abdominal pain and household size were negatively associated with Height for Age z-score. CONCLUSION: Age of the adolescents, gender, educational status, employment status and type of last school attended are associated with underweight; and gender, place of residence, household size, household income, educational status, employment status, type of last school attended and abdominal pain are associated with stunted. The findings reflect socio-demographic characteristics are associated with underweight and stunting. PMID- 26161176 TI - Malignant skin lesions in Oshogbo, Nigeria. AB - INTRODUCTION: The aim of this study is to retrospectively assess the prevalence of some of skin malignancies in our environment and to provide a data base for creating awareness for prevention and early detection of the diseases in order to reduce morbidity and mortality associated with these skin lesions in our environment. METHODS: This is a retrospective study of all histologically diagnosed malignant skin lesions which presented at Ladoke Akintola University of Technology Teaching Hospital Osogbo Osun State between January 2006 and December 2010. RESULTS: Ninety- eight patients presented with skin cancers out of which 60 (61.2%)were males and 38 (38.8%) were females. Malignant melanoma ranked highest followed by squamous cell carcinoma, dermatofibrosarcoma and basal cell carcinoma in that order. Malignant melanoma affects male more than female and it commonly affects lower limbs. CONCLUSION: Skin malignancies pose a burden to the economy of the country. Efforts should be directed toward prevention, early diagnosis and management in order to abolish or reduce morbidity, as well as mortality associated with late presentation of people in the developing countries. PMID- 26161177 TI - Hepatic primary neuroendocrine carcinoma: about a new case. AB - We report a new case of Primary hepatic neuroendocrine carcinoma admitted in our hospital and revealed in 53 years man by epigastric pain and flush syndrome. A liver biopsy with immunohistochemical study confirmed the original location of a neuroendocrine carcinoma. After 12 cures of Chemotherapy and a follow up of 12 months, the patient is still in complete remission. PMID- 26161178 TI - [EBV infection complicated with macrophage activation syndrome]. PMID- 26161179 TI - [Post traumatic thrombosis of the subclavian vein without right clavicle fracture: report of a case]. PMID- 26161180 TI - [Floating elbow combining Monteggia Bado 4 fracture to a fracture of the humerus plate]. PMID- 26161181 TI - [Morbidity and risk factors for neonatal mortality in Douala Referral Hospital]. PMID- 26161182 TI - [Cerebral venous thrombosis revealing Behcet disease in a child]. PMID- 26161183 TI - Knowledge and occupational hazards of barbers in the transmission of hepatitis B and C was low in Kumasi, Ghana. AB - INTRODUCTION: Blood borne viral hepatitis transmission still ranges between 4-20% in many Ghanaian communities. Hepatocellular carcinoma (HCC) also called liver cancer is reported as the leading cause of cancer mortality among males in Ghana. We studied the knowledge and risk factors associated with barbers' occupation in the transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: A randomized cross-sectional survey of 200 barbershops was conducted in Kumasi between January and August 2013. Barbershops, which operated continuously for more than 8 months, were selected for the study. Structured questionnaires were administered to the study participants. Data was entered and analysed in Microsoft Excel spread sheet and SPSS v12. The percentage value of each question was calculated. RESULTS: All the barbers involved in this study used a new razor blade on every client and claimed to sterilize the hair trimmers after use on every client. The methods of sterilization; 46.5% of the barbers used the ultraviolet radiation sterilizer cabinet, 29% used 70% alcohol and 23% used antiseptic solutions. More than thirty-six percent (36.5%) and 5% of the barbers had heard of HBV and HCV respectively. Only 7% and none knew the route of transmission of HBV and HCV respectively, whereas 7% knew sharing razor blade or hair trimmer could transmit both HBV and HCV. More so, 2% knew HBV and HCV could cause cancer and 2% had received the HBV vaccine. The majority of barbers (63%) had education up to the junior secondary school level. None of the barbers used a new apron nor washed their hands after work on each client. CONCLUSION: Awareness of barbers about HBV or HCV and job-related factors contributing to spread of infections was very poor among the vast majority of the barbers studied. Thus, giving training for the barbers is required toward prevention of blood- borne infections associated to their profession. PMID- 26161184 TI - Cervical spine injury in children: a case report and literature review. AB - Traumatic injuries of the cervical spine are less common in children than in adults. But may be associated with significant disability and mortality. Pediatric victims of blunt trauma have mechanisms of injury, developmental and anatomic characteristics different than the adults. The purpose of this observation is to highlight the differences between the adult and pediatric cervical spine. We report below the case of spinal cord cut occurs to a very young girl after a motor vehicle accident. PMID- 26161185 TI - Depressed skull fracture secondary to the Mayfield three-pin skull clamp. PMID- 26161186 TI - [Malignant anguillulosis of fatal outcome in pemphigus vegetans]. PMID- 26161187 TI - [Hyperemesis gravidarum with severe electrolyte disorders: report of a case]. PMID- 26161188 TI - Brachial artery injury following opened elbow dislocation associated with accessory brachial artery: two rare entities in a 17-year -old girl: case report. AB - Elbow dislocations are the most frequently encountered after shoulder dislocations. In their vast majority, these injuries carry a good prognosis. Although, concomitant arterial injury is rare and make them more serious. In this paper, we report a case of a 17 year old woman with opened elbow dislocation with arterial injury associated to an artery variation: "accessory brachial artery". PMID- 26161189 TI - Cervical plate fracture: a rare complication. AB - In traumatic and degenerative diseases cervical fusion with anterior cervical plate are commonly used. The increase in the use of cervical plate segment level is also increased risk of developing complications. This case report shows that the increase in the use of cervical plate segment level and also the complications in cervical spinal instrumentation, short-segment cervical plate rare case reported to be broken. PMID- 26161190 TI - [Isolated unilateral adrenal tuberculosis]. PMID- 26161192 TI - [Pancreatic neuroendocrine carcinoma: report of a case]. PMID- 26161191 TI - [Arthroscopic treatment of an articular fracture of the glenoid: new tip]. PMID- 26161193 TI - Partial substitution of the ureter using a double short segments of the ileum following the Monti procedure. AB - The partial substitution of the ureter using a pediculated double short segments of the ileum is a technique used to re-establish ureteral transit and preserve the renal unit, following the resection of extensive ureteral lesions. Standard surgical procedure for an ileoureteroplasty consists of isolating an ileal duct of equal or greater length than the ureteral defect and interposing it in the urinary tract in an isoperistaltic direction. Monti described a surgical technique that allows for the creation of catheterizable stomas in continent urinary diversions, using the Mitrofanoff principle. These passageways were created from one or several 2.5 cm long ileal sections by means of their detubulization and transverse retubulization. PMID- 26161194 TI - [Neonatal jejunal stenosis by incomplete double diaphragm]. PMID- 26161195 TI - [Total bilateral reverse shoulder prosthesis: about two cases]. PMID- 26161196 TI - [Risk factors for treatment adherence in patients with schizophrenia: case control study]. PMID- 26161197 TI - [Basal cell carcinoma in a Congolese (DRC) albinos: about one observation]. PMID- 26161198 TI - [Excavated persistent pulmonary opacities during a granulomatosis with polyangiitis: think of aspergillosis]. PMID- 26161199 TI - Factors associated with self medication practice among pregnant mothers attending antenatal care at governmental health centers in Bahir Dar city administration, Northwest Ethiopia, a cross sectional study. AB - INTRODUCTION: Studies in different parts of the world indicate that there is high level use of self medication among pregnant women. But there are no scientific evidences on it and factors associated with it in Bahir Dar city administration. The aim of this study was therefore to assess level of self medication and identify factors associated with it among pregnant women attending ANC service at governmental health centers in Bahir Dar city administration. METHODS: Institution based cross-sectional study was conducted from June 20-July 10, 2013. Data were collected using structured questionnaire and analyzed using SPSS version 16.0. Back ward logistic regression model was used to assess level of association with self medication practice. RESULTS: A total of 510 pregnant women were included in the study. Of these, 25.1% reported self-medication during the current pregnancy. Self medication during pregnancy was significantly associated with gravida (AOR = 2.1, 95% CI: 1.3-3.4), maternal illness on the date of interview (AOR = 4.8, 95% CI: 2.9-8.0) and location of health facility (AOR = 4.6; 95% CI: 2.9-7.4). CONCLUSION: A considerable proportion of pregnant women practiced self-medication during their pregnancy with modern medications or traditional herbs. Mothers who were multi gravida, who had maternal illness on the date of interview and who were attending antenatal care were more likely to practice self medication. PMID- 26161200 TI - Determinants of childhood vaccination completion at a peri-urban hospital in Kenya, December 2013 -January 2014: a case control study. AB - INTRODUCTION: Vaccine preventable diseases account for about 17% of deaths among children below five years in Kenya. Immunization is one the most cost-effective ways of reducing child mortality and morbidity worldwide. In Kenya, national full vaccination coverage today stands at above 80%. However there continue to be pockets of low full vaccination coverage like the catchment area of Alupe Sub District Hospital which pose a threat to the rest of the country. METHODS: This was a case-control study at Alupe Sub-District Hospital, Western Kenya. Sixty one (61) cases and 122 controls were sampled from the facility maternal and child health register by systematic random sampling and traced to their households. Cases were defined as children 12-23 months resident in Kenya who received at least one infant vaccine at the facility but were not fully vaccinated at the time of the study, while controls were children 12-23 months who were fully vaccinated by the time of the study. Pretested structured questionnaires were used for data collection. Data entry and analysis was done using Epi-Info 3.5.4 statistical software. RESULTS: Independent determinants of infant vaccination completion were the child's age < 18 months (AOR 4.2(1.8-9.6), p < 0.01), maternal age < 25 years (AOR 2.5(1.1-5.0), p = 0.03), maternal tetanus toxoid vaccination status < 2 TT doses (AOR 2.5(1.2-5.4), p < 0.02) and late receipt of BCG [AOR 3.2(1.4-7.3), p = 0.005). CONCLUSION: Strategies to increase full vaccination should target young mothers especially during antenatal period. PMID- 26161201 TI - [Systemic amyloidosis revealed by amyloid goiter]. PMID- 26161202 TI - [Invasive aspergillosis sinusitis in a diabetic]. PMID- 26161203 TI - Perihepatitis in systemic lupus erythematosus. PMID- 26161204 TI - Referral hospitals in the Democratic Republic of Congo as complex adaptive systems: similar program, different dynamics. AB - INTRODUCTION: In many African countries, first referral hospitals received little attention from development agencies until recently. We report the evolution of two of them in an unstable region like Eastern Democratic Republic of Congo when receiving the support from development aid program. Specifically, we aimed at studying how actors' network and institutional framework evolved over time and what could matter the most when looking at their performance in such an environment. METHODS: We performed two cases studies between 2006 and 2010. We used multiple sources of data: reports to document events; health information system for hospital services production, and "key-informants" interviews to interpret the relation between interventions and services production. Our analysis was inspired from complex adaptive system theory. It started from the analysis of events implementation, to explore interaction process between the main agents in each hospital, and the consequence it could have on hospital health services production. This led to the development of new theoretical propositions. RESULTS: Two events implemented in the frame of the development aid program were identified by most of the key-informants interviewed as having the greatest impact on hospital performance: the development of a hospital plan and the performance based financing. They resulted in contrasting interaction process between the main agents between the two hospitals. Two groups of services production were reviewed: consultation at outpatient department and admissions, and surgery. The evolution of both groups of services production were different between both hospitals. CONCLUSION: By studying two first referral hospitals through the lens of a Complex Adaptive System, their performance in a context of development aid takes a different meaning. Success is not only measured through increased hospital production but through meaningful process of hospital agents'" network adaptation. Expected process is not necessarily a change; strengthened equilibrium and existing institutional arrangement may be a preferable result. Much more attention should be given in future international aid to the proper understanding of the hospital adaptation capacities. PMID- 26161205 TI - [Blepharophimosis syndrome: a special form of congenital ptosis]. PMID- 26161206 TI - [Leiomyosarcoma of the inferior vena cava: a case report]. PMID- 26161207 TI - [Management of preterm labor on cervical-uterine incompetence using a pessary cerclage obstetrical]. PMID- 26161208 TI - [Should we prefer a surgical technique in the treatment of Achilles tendon ruptures?]. PMID- 26161209 TI - [A case of atypical non-traumatic spinal cord compression]. PMID- 26161210 TI - Oral and dental lesions in HIV infected Nigerian children. AB - INTRODUCTION: Oral diseases in the HIV infected children though commonly encountered are under researched and often overlooked by physicians in developing countries. The aim of this study is to document the types and frequency of oral lesions in HIV infected children and examine the effects of management with HAART on their rates. METHODS: A cross sectional study designed to identify the oral lesions in consecutive HIV infected children and their distribution at a Paediatric Anti-retroviral clinic. Information on oral disease and clinical features of the subjects were obtained by history and clinical examination and laboratory investigations by the pediatricians and dental surgeons. RESULTS: The 58 children studied consisted of 34 boys and 24 girls with their ages ranging from 3 months to 13 years. Thirty seven (63.8%) of the 58 children had oral diseases. Enamel hypoplasia, candidiasis, caries, angular chelitis, and herpes labialis were the most common oral lesions found in the patients. Oral soft tissue lesions were less frequently encountered among children on HAART. Statistical significance was recorded among those infected with candidiasis. More than 60% of the children diagnosed with oral disease had no knowledge of the state of their oral health before the study. CONCLUSION: Oral diseases are very common amongst the children studied. Awareness of oral disease among the children and their caregivers is low. Administration of HAART may have a preventive effect on the development of oral soft tissue disease. There is a need to integrate dental care into the paediatric HIV care programs. PMID- 26161211 TI - Fournier gangrene: rare complication of rectal cancer. AB - Fournier's Gangrene is a rare complication of rectal cancer. Its discovery is often delayed. It's incidence is about 0.3/100,000 populations in Western countries. We report a patient with peritoneal perforation of rectal cancer revealed by scrotal and perineal necrotizing fasciitis. PMID- 26161212 TI - [Rare nail tumor: molluscum fibroid or soft fibroma--about a case]. PMID- 26161213 TI - [Riedel thyroiditis]. PMID- 26161214 TI - [Surgical treatment of articular fractures of the calcaneus by bone plate]. PMID- 26161215 TI - [Pregnancy and kidney transplantation: report of 10 cases]. PMID- 26161216 TI - [Subarachnoid hemorrhage and parenchymal hematoma revealing a cerebral venous thrombosis]. PMID- 26161217 TI - [Hepatic cystadenoma simulating a hydatid cyst]. PMID- 26161218 TI - [Hydatid cyst of the liver: report of an unusual case]. PMID- 26161219 TI - [An unusual acute intestinal obstruction]. PMID- 26161220 TI - Oral verrucous carcinoma complicating a repetitive injury by the dental prosthesis: a case report. AB - Verrucous carcinoma (VC) is an unusual, well differentiated, and low-grade type of squamous cell carcinoma, characterized by benign histology and cytology but markedly invasive clinical behavior. They have a predilection for squamous mucosae, particularly those of the head and neck region. Many factors have been associated with its pathogenesis, including the presence of previous skin lesions; VC arising from a prosthesis injury is rare. Here we reported a case of VC of oral cavity a particularly very aggressive, arising from prosthesis injury. Regardless of the treatment modality, given new insights into the possible aggressivity of this tumor, radiotherapy associated to chemotherapy may be a more appropriate primary treatment compared with the significant local morbidity associated with surgery. PMID- 26161221 TI - [Laryngo-tracheobronchial foreign bodies: experience of the Teaching Hospital of the Armed Forced Omar Bongo Ondimba Libreville]. PMID- 26161222 TI - [Change in serum albumin in protein-energety malnutrition in a Congolese urban rural]. PMID- 26161223 TI - [Acute gastric volvulus on diaphragmatic hernia in adults: report of a case and review of literature]. PMID- 26161224 TI - [Unilateral bullous and purpuric lesions: skin pathomimicry]. PMID- 26161225 TI - Choroid plexus carcinoma in adults: an extremely rare case. AB - Choroid plexus tumors are rare intraventricular papillary neoplasms derived from choroid plexus epithelium, which account for approximately 2% to 4% of intracranial tumors in children and 0.5% in adults. Almost all choroid plexus carcinomas are seen in children and are extremely rare in adults. Headache, diplopia, and ataxia are the most common symptoms usually caused by mechanical obstruction of cerebrospinal fluid flow followed by hydrocephalus, regardless of tumor location. We present an illustrative case with 73 years old male patient who was consulted with headache to our neurosurgery department. In cranial computed tomography, there was a mass in 4(th) ventricle and we confirmed the mass with magnetic resonance imaging. After surgery had been performed, pathology specimen was diagnosed as choroid plexus carcinoma which was rarely seen in this age group. PMID- 26161226 TI - [Maternal factors associated with low birth weight: case-control study in a Moroccan public hospital]. PMID- 26161227 TI - [A textilome simulating an abdominal tumor]. PMID- 26161228 TI - [Superior vena cava syndrome secondary to the placement of a central venous catheter in a neonate]. PMID- 26161229 TI - Actinomycetoma of the arm disseminated to the chest wall. PMID- 26161230 TI - [Systemic sarcoidosis revealed by intracranial hypertension]. PMID- 26161231 TI - Hypopituitarism as consequence of late neonatal infection by Group B streptococcus: a case report. AB - Hypopituitarism is a condition characterized by dysfunction of the pituitary gland hormone production. The insults of the perinatal period, which includes the late infection by Group B Streptococcus, consists in a rare etiology of this condition. We present the case of a 39-days-old infant with meningitis caused by Streptococcus Group B, which showed, among other consequences, hypopituitarism. PMID- 26161232 TI - An exceptional case of bilateral gestational gigantomastia with multiple breast lumps. AB - Bilateral gigantomastia is a rare condition, often associated with pregnancy that is characterized by a diffuse enlargement of both breasts. Here we present a case of a late 20s woman in her seven months pregnancy with a bilateral gestational gigantomastia associated with multiple breast lumps. Histological analysis revealed a fibroadenoma. Her prolactin level after caesarean delivery was found particularly high. A significant decrease in breast size was achieved with bromocriptine treatment in conjunction with a bilateral lumpectomy. This case report highlights the diversity of gigantomastia and emphasizes the importance of a tailored, multidisciplinary approach to the diagnosis and treatment of this condition. PMID- 26161233 TI - [Ventricular septal defect post circumferential myocardial infarction: report of a case and review of literature]. PMID- 26161234 TI - High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery. AB - Objective. Ischemia/reperfusion (I/R) injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB). This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb), a hemoglobin-based oxygen carrier (HBOC), can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v) provided a significant protection on the I/R heart, whereas the high dose PolyPHb (3%, w/v) did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs) to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, and elevated malonaldehyde (MDA) formation. Consistent with the increased oxidative stress, the NAD(P)H oxidase activity and subunits expression, including gp91(phox), p47(phox), p67(phox), and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(P)H oxidase-induced ROS and resultant endothelial dysfunction. PMID- 26161235 TI - Mechanical Ventilation Induces an Inflammatory Response in Preinjured Lungs in Late Phase of Sepsis. AB - Mechanical ventilation (MV) may amplify the lung-specific inflammatory response in preinjured lungs by elevating cytokine release and augmenting damage to the alveolar integrity. In this study, we test the hypothesis that MV exerts different negative impacts on inflammatory response at different time points of postlung injury. Basic lung injury was induced by cecal ligation and puncture (CLP) surgery in rats. Physiological indexes including blood gases were monitored during MV and samples were assessed following each experiment. Low V T (tidal volume) MV caused a slight increase in cytokine release and tissue damage at day 1 and day 4 after sepsis induced lung injury, while cytokine release from the lungs in the two moderately ventilated V T groups was amplified. Interestingly, in the two groups where rats received low V T MV, we found that infiltration of inflammatory cells was only profound at day 4 after CLP. Marked elevation of protein leakage indicated a compromise in alveolar integrity in rats that received moderate V T MV at day 4 following CLP, correlating with architectural damage to the alveoli. Our study indicates that preinjured lungs are more sensitive to mechanical MV at later phases of sepsis, and this situation may be a result of differing immune status. PMID- 26161236 TI - Preventive Treatment with Ketamine Attenuates the Ischaemia-Reperfusion Response in a Chronic Postischaemia Pain Model. AB - Ischemia and inflammation may be pathophysiological mechanisms of complex regional pain syndrome (CRPS). Ketamine has proposed anti-inflammatory effects and has been used for treating CRPS. This study aimed to evaluate anti inflammatory and analgesic effects of ketamine after ischaemia-reperfusion injury in a chronic postischaemia pain (CPIP) model of CRPS-I. Using this model, ischemia was induced in the hindlimbs of male Sprague-Dawley rats. Ketamine, methylprednisolone, or saline was administered immediately after reperfusion. Physical effects, (oedema, temperature, and mechanical and cold allodynia) in the bilateral hindpaws, were assessed from 48 hours after reperfusion. Fewer (56%) rats in the ketamine group developed CPIP at the 48th hour after reperfusion (nonsignificant). Ketamine treated rats showed a significantly lower temperature in the ischaemic hindpaw compared to saline (P < 0.01) and methylprednisolone (P < 0.05) groups. Mechanical and cold allodynia were significantly lower in the ischaemic side in the ketamine group (P < 0.05). Proinflammatory cytokines TNF alpha and IL-2 were significantly lower at the 48th hour after reperfusion in ketamine and methylprednisolone groups, compared to saline (all P < 0.05). In conclusion, immediate administration of ketamine after an ischaemia-reperfusion injury can alleviate pain and inflammation in the CPIP model and has potential to treat postischaemic pain. PMID- 26161237 TI - Glutathione Supplementation Attenuates Oxidative Stress and Improves Vascular Hyporesponsiveness in Experimental Obstructive Jaundice. AB - We investigated the protective effects and mechanism of glutathione (GSH) on vascular hyporesponsiveness induced by bile duct ligation (BDL) in a rat model. Seventy-two male Sprague-Dawley rats were randomly divided into four groups: a NS group, a GSH group, a BDL + NS group, and a BDL + GSH group. GSH was administrated into rats in the GSH and BDL + GSH groups by gastric gavage. An equal volume of normal saline was, respectively, given in the NS group and BDL + NS group. Blood was gathered for serological determination and thoracic aorta rings were isolated for measurement of isometric tension. Obstructive jaundice led to a significant increase in the serum total bilirubin, AST, and ALT levels. The proinflammatory cytokines levels (TNF-alpha and IL-1beta), concentration of NO, and oxidative stress markers (MDA and 3-NT) were increased as well. All of those were reduced by the treatment of GSH. Meanwhile, contraction of aorta rings to NA and vasorelaxation to ACh or SNP in the BDL group rats were markedly decreased, while GSH administration reversed this change. Our findings suggested that GSH supplementation attenuated overexpressed ONOO(-) from the reaction of excessive NO with O2 (?-) and protected against obstructive jaundice-induced vascular hyporesponsiveness in rats. PMID- 26161239 TI - Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway. AB - BACKGROUND: Activation of the adenosine A2B receptor (A2BR) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying the A2BR mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated by A2BR. METHODS AND RESULTS: C57BL/6 mice underwent 40-minute ischemia and 60-minute reperfusion. ATL-801, a potent selective A2BR antagonist, could not block ischemic preconditioning induced protection. BAY 60-6583, a highly selective A2BR agonist, significantly reduced myocardial infarct size, and its protective effect could be blocked by either ATL-801 or wortmannin. BAY 60-6583 increased phosphorylated Akt (p-Akt) levels in the heart at 10 min of reperfusion, and this phosphorylation could also be blocked by ATL-801 or wortmannin. Furthermore, BAY 60-6583 significantly increased M2 macrophages and decreased M1 macrophage and neutrophils infiltration in reperfused hearts, which also could be blocked by wortmannin. Meanwhile, confocal imaging studies showed that the majority of Akt phosphorylation in the heart was colocalized to CD206+ cells in both control and BAY 60-6583 pretreated hearts. CONCLUSION: Our results indicated that pretreatment with BAY 60-6583 protects the heart against myocardial IR injury by its anti-inflammatory effects, probably by modulating macrophages phenotype switching via a PI3K/Akt pathway. PMID- 26161238 TI - Organ-Protective Effects of Red Wine Extract, Resveratrol, in Oxidative Stress Mediated Reperfusion Injury. AB - Resveratrol, a polyphenol extracted from red wine, possesses potential antioxidative and anti-inflammatory effects, including the reduction of free radicals and proinflammatory mediators overproduction, the alteration of the expression of adhesion molecules, and the inhibition of neutrophil function. A growing body of evidence indicates that resveratrol plays an important role in reducing organ damage following ischemia- and hemorrhage-induced reperfusion injury. Such protective phenomenon is reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed. PMID- 26161241 TI - Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits. AB - Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties. PMID- 26161240 TI - Oxidative Stress and Lung Ischemia-Reperfusion Injury. AB - Ischemia-reperfusion (IR) injury is directly related to the formation of reactive oxygen species (ROS), endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients. PMID- 26161242 TI - OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells. AB - Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8 oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use. PMID- 26161244 TI - RETROSPECTIVE DETECTION OF INTERLEAVED SLICE ACQUISITION PARAMETERS FROM FMRI DATA. AB - To minimize slice excitation leakage to adjacent slices, interleaved slice acquisition is nowadays performed regularly in fMRI scanners. In interleaved slice acquisition, the number of slices skipped between two consecutive slice acquisitions is often referred to as the 'interleave parameter'; the loss of this parameter can be catastrophic for the analysis of fMRI data. In this article we present a method to retrospectively detect the interleave parameter and the axis in which it is applied. Our method relies on the smoothness of the temporal distance correlation function, which becomes disrupted along the axis on which interleaved slice acquisition is applied. We examined this method on simulated and real data in the presence of fMRI artifacts such as physiological noise, motion, etc. We also examined the reliability of this method in detecting different types of interleave parameters and demonstrated an accuracy of about 94% in more than 1000 real fMRI scans. PMID- 26161243 TI - Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice. AB - Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway. Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R. Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) alpha but decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF alpha and MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA. Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway. PMID- 26161245 TI - The role of fluoride tablets in the prophylaxis of dental caries. A literature review. AB - AIM: Doing a meta-analysis to answer the question: "Does fluoride tablets prevent dental caries among children and adolescents?" MATERIALS AND METHODS: A review of the literature is performed using the following databases: PubMed, Embase, CINAHL, Cochrane Library, Embase, NHS Evidence Oral Health, PsycINFO, Web of Knowledge, Metalib. The keywords used are dental fluoride, fluoride tablets. The studies analyzed was limited to English language with free abstract. For the studies selection was taken into consideration the criteria proposed by the Cochrane Oral Health Group. RESULTS: Few studies with good quality were identified in general. Only 3 out of 779 studies were acceptable. CONCLUSIONS: Evident disagreements among the results show that there's a limited effectiveness on fluoride tablets. PMID- 26161246 TI - Deformations and cyclic fatigue resistance of nickel-titanium instruments inside a sequence. AB - AIM: To compare the effect of brushing motion on torsional and cyclic fatigue resistance of TF Adaptive instruments after clinical use. METHODS: 20 packs of TFA small sequence (SybronEndo, Orange, CA, USA) were used for this study and divided into two groups. Each instrument prepared one resin tooth, consisting in 4 canals with a complex anatomy. In group A, no brushing motion was performed. In group B, after the green instrument reached the working length, brushing motion with circumferential filing was performed for 15 seconds in each canal (overall 1 minute). All the instruments were then subjected to cyclic fatigue test and mean values and standard deviation for time to fracture were evaluated. Data were subjected to one-way analysis of variance and Bonferroni t-test procedure with a significance set at P < 0.05. RESULTS: No instruments were broken during preparation of root canals. Two TF Adaptive green and 5 yellow showed unwinding after intracanal clinical use. No statistically significant differences were found between green instruments of both groups (P > 0.05), while a statistically significant difference was found between the yellow instruments (P < 0.05), with group B showing an higher resistance to cyclic fatigue. CONCLUSIONS: A prolonged passive brushing motion did not adversely affected mechanical resistance of the instrument used for this purpose. Resistance to both deformations and cyclic fatigue of the second instrument within the TFA small sequence was enhanced by the coronal flaring provided by the brushing action of the first instrument used. PMID- 26161247 TI - Evaluation of over-etching technique in the endodontically treated tooth restoration. AB - The main purpose of a post-endodontic restoration with posts is to guarantee the retention of the restorative material. The aim of the study was to examine, through the push-out test, how bond strength between the post and the dentin varied with etching time with 37% orthophosphoric acid, before cementation of a glass fiber post. Moreover, it has been examined if over-etching (application time of the acid: 2 minutes) was an effective technique to improve the adhesion to the endodontic substrate, after highlighting the problems of adhesion concerning its anatomical characteristics and the changes after the endodontic treatment. Highest bond strength values were found by etching the substrate for 30 sec., while over-etching didn't improve bond strength to the endodontic substrate. PMID- 26161248 TI - Effectiveness of a diode laser in addition to non-surgical periodontal therapy: study of intervention. AB - BACKGROUND: Chronic periodontitis affects 47% of adult population over the age of 30. The first phase of periodontal treatment is always represented by scaling and root planning (SRP), that is a causal, non-surgical therapy that recognizes as primary aims the control of bacterial infection and the reduction of periodontal plaque-associated inflammation. Yet, another innovative causal therapy is represented by the irradiation of periodontal pockets with laser. AIM: To evaluate the effect of a 940-nm diode laser as an adjunct to SRP in patients affected by periodontitis. MATERIALS AND METHODS: Sixty-eight adult patients with moderate-to-severe periodontitis were sequentially enrolled and undergone to periodontal examination (V1) in order to detect gingival index (GI), plaque index (PI) and probing depth (PD). The patients were randomly divided into two groups: the first (n=34) received SRP treatment alone, the control group (n=34) received SRP and 940-nm diode laser therapy. RESULTS: Data were analyzed by Student's t test, with two tails; for all clinical parameters, both groups reported statistically significant differences compared to basal values (p<0.0001). Both procedures were effective in improving GI, PI and PD, but the use of diode laser was associated with more evident results. CONCLUSIONS: Considered the better clinical outcomes, diode laser can be routinely associated with SRP in the treatment of periodontal pockets of patients with moderate-to-severe periodontitis. PMID- 26161249 TI - The impact of smoking and previous periodontal disease on peri-implant microbiota and health: a retrospective study up to 7-year follow-up. AB - AIM: To evaluate the impact of smoking and previous periodontal disease on peri implant microbiota and health in medium to long-term maintained patients. METHODS: A retrospective evaluation of partial edentulous patients restored with dental implants and enrolled in a regular supportive therapy was performed. Inclusion criteria were: medium to long-term periodontal and implant maintenance (at least 5 years), a minimum of 2 implants placed in each patient, absence of systemic diseases that may affect osseointegration. 30 implants in 15 patients were included in the study. Subjects were divided in smokers or non-smokers and between patients previously affected by periodontal disease and periodontally healthy. Peri-implant and periodontal parameters were assessed (PD,BoP, mPI). Microbiological samples were collected around implant and an adjacent tooth. Real Time Polymerase Chain Reaction (RT-PCR) analysis was performed. RESULTS: In all the three groups no differences in bacterial counts between dental and implant sites were observed. Non smoker, healthy patients: healthy clinical parameters, significant counts of spirochetes in isolated patients. Non smokers with previous periodontal disease: occasional positive BoP values, significant high counts of pathogenic bacteria. Smokers with previous periodontal disease: clinical signs of inflammation including deep pockets and slight bone resorption, significant counts of pathogenic bacteria. CONCLUSIONS: Over a follow-up of 5 to 7 years, it is possible to state that the absence of smoking habit and previous periodontal disease positively influences the peri-implant microbiological and clinical conditions in partial edentulous patients restored with dental implants and enrolled in a strict regular supportive therapy. PMID- 26161250 TI - Postextractive implants in aesthetic areas: evaluation of perimplant bone remodeling over time. AB - AIM: The aim of this research was to assess peri-implant bone remodeling of post extractive implants over 2 years. MATERIAL AND METHODS: 30 patients meeting pre established inclusion criteria were enrolled for the study. One implant for each patient was inserted in the post-extraction sockets according to a defined surgical protocol (atramautic extraction, curettage of extraction socket, implant insertion, grafting with collagenated cortico-cancellous porcine bone, and a trimmed collagen membrane to completely cover the socket, suture). A temporary adhesive bridge, with an adequate profile, was bonded to the adjacent teeth. X ray evaluation with a standardized stent was carried out at different times. Measurements were obtained from the implant edge to the bone peak. The values obtained at time 0 and at 2 years were compared by t-student test. RESULT: Our results showed that after one year 73% of patient had 0 mm of bone reabsorption, 20% of patient had 0 mm <= x <= 0.5mm, 7% of patient had 0.5 mm <= x <= 2 mm of bone reabsorption. After two years 62% of patient had 0 mm of bone reabsorption, 24% had 0 mm <= x <= 0.5mm, 14% had 0.5 mm <= x <= 2 mm. CONCLUSIONS: The results showed no significant differences in bone reabsorption in most patients over 2 years. PMID- 26161251 TI - Methanocarba ring as a ribose modification in ligands of G protein-coupled purine and pyrimidine receptors: synthetic approaches. AB - Adenosine receptors (ARs) and P2Y receptors for purine and pyrimidine nucleotides have widespread distribution and regulate countless physiological processes. Various synthetic ligands are in clinical trials for treatment of inflammatory diseases, pain, cancer, thrombosis, ischemia, and other conditions. The methanocarba (bicyclo[3.1.0]hexane) ring system as a rigid substitution for ribose, which maintains either a North (N) or South (S) conformation, tends to preserve or enhance the potency and/or selectivity for certain receptor subtypes. This review summarizes recent developments in the synthetic approaches to these biologically important nucleoside and nucleotide analogues. PMID- 26161252 TI - 4-Alkyloxyimino-cytosine nucleotides: tethering approaches to molecular probes for the P2Y6 receptor. AB - 4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists of certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y6R agonist for fluorescent labeling, we probed two positions (N4 and gamma-phosphate of cytidine derivatives) with various functional groups, including alkynes for click chemistry. Functionalization of extended imino substituents at the 4 position of the pyrimidine nucleobase of CDP preserved P2Y6R potency generally better than gamma-phosphoester formation in CTP derivatives. Fluorescent Alexa Fluor 488 conjugate 16 activated the human P2Y6R expressed in 1321N1 human astrocytoma cells with an EC50 of 9 nM, and exhibited high selectivity for this receptor over other uridine nucleotide-activated P2Y receptors. Flow cytometry detected specific labeling with 16 to P2Y6R-expressing but not to wild-type 1321N1 cells. Additionally, confocal microscopy indicated both internalized 16 (t1/2 of 18 min) and surface-bound fluorescence. Known P2Y6R ligands inhibited labeling. Theoretical docking of 16 to a homology model of the P2Y6R predicted electrostatic interactions between the fluorophore and extracellular portion of TM3. Thus, we have identified the N4-benzyloxy group as a structurally permissive site for synthesis of functionalized congeners leading to high affinity molecular probes for studying the P2Y6R. PMID- 26161253 TI - Muscle dysfunction associated with adjuvant-induced arthritis is prevented by antioxidant treatment. AB - BACKGROUND: In addition to the primary symptoms arising from inflamed joints, muscle weakness is prominent and frequent in patients with rheumatoid arthritis (RA). Here, we investigated the mechanisms of arthritis-induced muscle dysfunction in rats with adjuvant-induced arthritis (AIA). METHODS: AIA was induced in the knees of rats by injection of complete Freund's adjuvant and was allowed to develop for 21 days. Muscle contractile function was assessed in isolated extensor digitorum longus (EDL) muscles. To assess mechanisms underlying contractile dysfunction, we measured redox modifications, redox enzymes and inflammatory mediators, and activity of actomyosin ATPase and sarcoplasmic reticulum (SR) Ca(2+)-ATPase. RESULTS: EDL muscles from AIA rats showed decreased tetanic force per cross-sectional area and slowed twitch contraction and relaxation. These contractile dysfunctions in AIA muscles were accompanied by marked decreases in actomyosin ATPase and SR Ca(2+)-ATPase activities. Actin aggregates were observed in AIA muscles, and these contained high levels of 3 nitrotyrosine and malondialdehyde-protein adducts. AIA muscles showed increased protein expression of NADPH oxidase 2/gp91(phox), neuronal nitric oxide synthase, tumor necrosis factor alpha (TNF-alpha), and high-mobility group box 1 (HMGB1). Treatment of AIA rats with EUK-134 (3 mg/kg/day), a superoxide dismutase/catalase mimetic, prevented both the decrease in tetanic force and the formation of actin aggregates in EDL muscles without having any beneficial effect on the arthritis development. CONCLUSIONS: Antioxidant treatment prevented the development of oxidant-induced actin aggregates and contractile dysfunction in the skeletal muscle of AIA rats. This implies that antioxidant treatment can be used to effectively counteract muscle weakness in inflammatory conditions. PMID- 26161254 TI - Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry. AB - BACKGROUND: Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry. Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU). RESULTS: During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety. CONCLUSIONS: Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets. PMID- 26161255 TI - Therapeutic manipulation of angiogenesis with miR-27b. AB - BACKGROUND: Multiple studies demonstrated pro-angiogenic effects of microRNA (miR)-27b. Its targets include Notch ligand Dll4, Sprouty (Spry)-2, PPARgamma and Semaphorin (SEMA) 6A. miR-27 effects in the heart are context-dependent: although it is necessary for ventricular maturation, targeted overexpression in cardiomyocytes causes hypertrophy and dysfunction during development. Despite significant recent advances, therapeutic potential of miR-27b in cardiovascular disease and its effects in adult heart remain unexplored. Here, we assessed the therapeutic potential of miR-27b mimics and inhibitors in rodent models of ischemic disease and cancer. METHODS: We have used a number of models to demonstrate the effects of miR-27b mimicry and inhibition in vivo, including subcutaneous Matrigel plug assay, mouse models of hind limb ischemia and myocardial infarction and subcutaneous Lewis Lung carcinoma. RESULTS: Using mouse model of myocardial infarction due to the coronary artery ligation, we showed that miR-27b mimic had overall beneficial effects, including increased vascularization, decreased fibrosis and increased ejection fraction. In mouse model of critical limb ischemia, miR-27b mimic also improved tissue re vascularization and perfusion. In both models, miR-27b mimic clearly decreased macrophage recruitment to the site of hypoxic injury. In contrast, miR-27b increased the recruitment of bone marrow derived cells to the neovasculature, as was shown using mice reconstituted with fluorescence-tagged bone marrow. These effects were due, at least in part, to the decreased expression of Dll4, PPARgamma and IL10. In contrast, blocking miR-27b significantly decreased vascularization and reduced growth of subcutaneous tumors and decreased BMDCs recruitment to the tumor vasculature. CONCLUSIONS: Our study demonstrates the utility of manipulating miR-27b levels in the treatment of cardiovascular disease and cancer. PMID- 25717370 TI - Detection of Burkholderia pseudomallei in Sputum using Selective Enrichment Broth and Ashdown's Medium at Kampong Cham Provincial Hospital, Cambodia. AB - Melioidosis, infection caused by Burkholderia pseudomallei, is increasingly reported in Cambodia. We hypothesized that implementation of an enhanced sputum testing protocol in a provincial hospital diagnostic microbiology laboratory would increase detection of B. pseudomallei. We tested 241 sputum specimens that were deemed acceptable for culture, comparing culture in selective enrichment broth followed by sub-culture on Ashdown's medium to standard culture methods. Two specimens (0.8%) were positive for B. pseudomallei using the enhanced protocol whereas one specimen (0.4%) was positive using standard methods. Given the low numbers of positive specimens, we could not conclusively determine the utility of the enhanced sputum testing protocol. However, the ramifications of identification of B. pseudomallei are substantial, and the benefit of the enhanced testing protocol may be more apparent in patients selected based on risk factors and clinical presentation. Promoting clinician awareness of the infection and encouraging utilization of diagnostic microbiology services are also likely to be important factors in facilitating identification of melioidosis. PMID- 26161257 TI - Erratum: SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler. AB - [This corrects the article DOI: 10.1186/2047-217X-1-18.]. PMID- 26161258 TI - Colony-stimulating factors for chemotherapy-related febrile neutropenia are associated with improved prognosis in adult acute lymphoblastic leukemia. AB - Colony-stimulating factors (CSF) have been widely used to prevent febrile neutropenia associated with chemotherapy. Due to the high intensity of chemotherapy in acute lymphoblastic leukemia (ALL), CSF as a crucial component of supportive care has played a significant role in the therapy. However, the effectiveness of CSF in treatment has not been identified by large clinical trials until now. The aim of the present study was to evaluate the effect of CSF on the long-term outcome of adult ALL patients. A comprehensive search strategy has been conducted, which covered the Cochrane Central Register of Controlled Trials, PubMed and Web of Science. The result includes seven randomized controlled trials containing a total of 753 patients. The administration of CSF significantly reduced the mortality at the end of the follow-up (RR, 0.85; 95% CI, 0.75-0.95), the mortality at day 30 (RR, 0.41; 95% CI, 0.23-0.74) and the number of patients with infection or severe infections (RR, 0.8; 95% CI, 0.7-0.9 and RR, 0.48; 95% CI, 0.3-0.75). The addition of CSF also marginally increased the number of patients achieving CR (RR, 1.14; 95% CI, 1.05-1.23). The use of CSF also shortened the duration of neutropenia (median days, 8-17 to 12.5-24). In conclusion, CSFs can be administered to ALL patients during myelosuppressive chemotherapy, particularly in the induction phase. PMID- 26161259 TI - Triptolide potentiates lung cancer cells to cisplatin-induced apoptosis by selectively inhibiting the NER activity. AB - BACKGROUND: Cisplatin and many other platinum-based compounds are important anticancer drugs that are used in treating many cancer types. The development of cisplatin-resistant cancer cells, however, quickly diminishes the effectiveness of these drugs and causes treatment failure. New strategies that reverse cancer cell drug resistance phenotype or sensitize cancer cells to these drugs, therefore, need to be explored in order to improve platinum drug-based cancer treatment. Triptolide is a bioactive ingredient isolated from Tripterygium wilfordii, a Chinese herbal medicine. Triptolide binds to the TFIIH basal transcription factor and is required for both transcription and nucleotide excision repair (NER), a DNA repair pathway involved in repairing DNA damage generated by the platinum-based anticancer drugs. METHODS: Caspase-3 activation and cell growth inhibition assays were used to determine the effect of triptolide on cisplatin-induced apoptosis and cell growth in lung cancer cells. Real time PCR, immunoblotting, and expression of reef coral red protein were used to determine a mechanism through which the presence of triptolide increased cisplatin-induced apoptosis of the lung cancer cells. RESULTS: Our caspase-3 activation studies demonstrated that the presence of low-levels of triptolide greatly increased the cisplatin-induced apoptosis of HTB182, A549, CRL5810, and CRL5922 lung cancer cells. The results of our cell growth inhibition studies revealed that the presence of low-levels triptolide itself had little effect on cell growth but greatly enhanced cisplatin-induced cell growth inhibition in both A549 and HTB182 cells. The results of our reef coral-red protein reporter expression studies indicated that the presence of low-levels triptolide did not affect expression of the reef coral-red protein from pDsRed2-C1 plasmid but greatly inhibited expression of the reef coral-red protein from cisplatin-damaged pDsRed2-C1 plasmid DNA in A549 cells. In addition, the results of our protein phosphorylation studies indicated that the presence of low-levels triptolide caused a decrease for cisplatin-induced CHK1 phosphorylation at Ser(317/345) but an increase for cisplatin-induced ATM phosphorylation at Ser(1981) in both HTB182 and A549 cells. CONCLUSION: The results of our studies suggest that the presence of low-levels of triptolide potentiates lung cancer cells to cisplatin treatment by selectively inhibiting NER activity, resulting in an increase in apoptosis of the lung cancer cells. PMID- 26161260 TI - Opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia. AB - Adrenal insufficiency is a rare cause of hypercalcaemia and should be considered when more common causes such as primary hyperparathyroidism and malignancy are excluded. Opioid therapy as a cause of adrenal insufficiency is a possibly under recognised endocrinopathy with potentially life-threatening adverse effects. We report on a case of opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia. The patient was a 25-year-old man who developed hypercalcaemia during the recovery stage after a period of critical illness. Systematic investigation of his hypercalcaemia found it to be due to secondary adrenal insufficiency, developing as a consequence of methadone opioid analgesia. Treatment with i.v. saline and subsequent glucocorticoid replacement led to resolution of the hypercalcaemia. The hypoadrenalism resolved when opioids were subsequently weaned and ceased. These two interacting endocrinopathies of opioid induced adrenal insufficiency and consequent hypercalcaemia highlight the importance of maintaining awareness of the potentially serious adverse clinical outcomes which can occur as a result of opioids, particularly considering that symptoms of hypoadrenalism can overlap with those of concomitant illness. Treatment with hydration and glucocorticoid replacement is effective in promptly resolving the hypercalcaemia due to hypoadrenalism. Hypoadrenalism due to prescribed and recreational opioids may be more common than is currently recognised. LEARNING POINTS: Opioid therapy can cause clinically significant secondary adrenal insufficiency, and this may be more common than is currently recognised.Adrenal insufficiency is reversible after discontinuation of the opioid therapy.Hypercalcaemia can occur as a consequence of adrenal insufficiency, and may be the presenting feature.Treatment of hypercalcaemia due to adrenal insufficiency involves i.v. saline and glucocorticoid replacement. PMID- 26161261 TI - Successful treatment of neonatal severe hyperparathyroidism with cinacalcet in two patients. AB - Neonatal severe hyperparathyroidism (NSHPT) is a rare disorder caused by inactivating calcium-sensing receptor (CASR) mutations that result in life threatening hypercalcemia and metabolic bone disease. Until recently, therapy has been surgical parathyroidectomy. Three previous case reports have shown successful medical management of NSHPT with cinacalcet. Here we present the detailed description of two unrelated patients with NSHPT due to heterozygous R185Q CASR mutations. Patient 1 was diagnosed at 11 months of age and had developmental delays, dysphagia, bell-shaped chest, and periosteal bone reactions. Patient 2 was diagnosed at 1 month of age and had failure to thrive, osteopenia, and multiple rib fractures. Cinacalcet was initiated at 13 months of age in patient 1, and at 4 months of age in patient 2. We have successfully normalized their parathyroid hormone and alkaline phosphatase levels. Despite the continuance of mild hypercalcemia (11-12 mg/dl), both patients showed no hypercalcemic symptoms. Importantly, patient 1 had improved neurodevelopment and patient 2 never experienced any developmental delays after starting cinacalcet. Neither experienced fractures after starting cinacalcet. Both have been successfully managed long-term without any significant adverse events. These cases expand the current literature of cinacalcet use in NSHPT to five successful reported cases. We propose that cinacalcet may be considered as an option for treating the severe hypercalcemia and metabolic bone disease found in infants and children with inactivating CASR disorders. LEARNING POINTS: NSHPT due to mutations in the CASR gene occurs with hypercalcemia and metabolic bone disease, but not always with severe critical illness in infancy.NSHPT should be considered in the differential diagnosis for a newborn with a bell-shaped chest, osteopenia, and periosteal reactions.Neurodevelopmental consequences may occur in children with hypercalcemia and may improve during treatment.Calcimimetics can be used to successfully treat the pathophysiology of NSHPT directly to control serum calcium levels. PMID- 26161263 TI - Warmth Trumps Competence in Evaluations of Both Ingroup and Outgroup. AB - Research from a number of social psychological traditions suggests that social perceivers should be more concerned with evaluating others' intentions (i.e., warmth) relative to evaluating others' ability to act on those intentions (i.e., competence). The present research examined whether warmth evaluations have cognitive primacy over competence evaluations in a direct reaction-time comparison and whether the effect is moderated by ingroup versus outgroup membership. Participants evaluated as quickly as possible whether warmth versus competence traits described photographs of racial ingroup versus outgroup members expressing neutral emotions. Responses supported the hypothesis that evaluations of warmth take precedence over evaluations of competence; participants were faster to evaluate others on warmth-related traits compared to competence-related traits. Moreover, this primacy effect was not moderated by racial group membership. The data from this research speak to the robustness of the primacy of warmth in social evaluation. PMID- 26161264 TI - Inaugural Message from the Founding Editor-in-Chief. PMID- 26161262 TI - A quantitative assessment of the content of hematopoietic stem cells in mouse and human endosteal-bone marrow: a simple and rapid method for the isolation of mouse central bone marrow. AB - BACKGROUND: Isolation of bone marrow cells, including hematopoietic stem cells, is a commonly used technique in both the research and clinical settings. A quantitative and qualitative assessment of cell populations isolated from mouse and human bone marrow was undertaken with a focus on the distribution of hematopoietic cells between the central bone marrow (cBM) and endosteal bone marrow (eBM). METHODS: Two approaches to cBM isolation from the hind legs were compared using the C57BL/6J and BALB/cJ strains of laboratory mice. The content of hematopoietic stem cells in eBM was compared to cBM from mice and human fetal bone marrow using flow cytometry. Enzymatic digestion was used to isolate eBM and its effects on antigen expression was evaluated using flow cytometry. Humanized immunodeficient mice were used to evaluate the engraftment of human precursors in the cBM and eBM and the effects of in vivo maturation on the fetal stem cell phenotype were determined. RESULTS: The two methods of mouse cBM isolation yielded similar numbers of cells from the femur, but the faster single-cut method recovered more cells from the tibia. Isolation of eBM increased the yield of mouse and human stem cells. Enzymatic digestion used to isolate eBM did, however, have a detrimental effect on detecting the expression of the human HSC-antigens CD4, CD90 and CD93, whereas CD34, CD38, CD133 and HLA-DR were unaffected. Human fetal HSCs were capable of engrafting the eBM of immunodeficient mice and their pattern of CD13, CD33 and HLA-DR expression partially changed to an adult pattern of expression about 1 year after transplantation. CONCLUSIONS: A simple, rapid and efficient method for the isolation of cBM from the femora and tibiae of mice is detailed. Harvest of tibial cBM yielded about half as many cells as from the femora, representing 6.4 % and 13 %, respectively, of the total cBM of a mouse based on our analysis and a review of the literature. HSC populations were enriched within the eBM and the yield of HSCs from the mouse and human long bones was increased notably by harvest of eBM. PMID- 26161265 TI - Soil-Transmitted Helminth Infections and Associated Risk Factors among Schoolchildren in Durbete Town, Northwestern Ethiopia. AB - Identifying determinants of soil transmitted helminth infection is vital to design control strategy for the disease. This study assessed the prevalence of STH infections and associated factors among schoolchildren in Durbete town, northwestern Ethiopia. Data about the sociodemographic and socioeconomic status of the children were collected using a questionnaire and stool samples were diagnosed using thick Kato-Katz smear. STH infection was more common among school age children in Durbete town. Hookworm was the most frequent helminth species detected. The prevalence of STH infection was more in children who did not practice wearing shoes and washing hands before eating and in those who were older in age. Deworming of school-age children in the study area would be important. In addition, provision of health education about helminths and the importance of wearing shoes and washing hands before eating would be important to reduce the burden of STH infection in the study area. PMID- 26161266 TI - The Influence of a Vitrectomy on the Diurnal Intraocular Pressure. AB - Purpose. To evaluate the diurnal intraocular pressure (IOP) in eyes after vitrectomy compared to that of healthy eyes. Methods. Twenty-one patients who had undergone vitrectomy and 21 age- and gender-matched normal controls were enrolled during the same period. We measured the diurnal IOP every two hours between 9 a.m. and 11 p.m. in all patients who were admitted for cataract surgery. Patients with a history of eye surgery (not including vitrectomy) or use of a medication that is associated with IOP were excluded. The IOP and ocular parameters of patients were compared with the same patients' fellow healthy eyes and with normal eyes of age- and gender-matched controls. Results. There were no significant differences between vitrectomized eyes and normal fellow eyes with regard to all IOP parameters including the maximum, minimum, and IOP fluctuation values. Diurnal fluctuation of IOP (or the difference between the maximum and minimum IOP) was larger in vitrectomized eyes than it was in age- and gender matched control eyes. Conclusions. Vitrectomy did not markedly affect the IOP. Although there were no severe complications after vitrectomy, the IOP fluctuation was wider in vitrectomized eyes than it was in normal eyes. PMID- 26161267 TI - Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations. AB - The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD. PMID- 26161269 TI - Cumulative Weight Exposure Is Associated with Different Weight Loss Strategies and Weight Loss Success in Adults Age 50 or Above. AB - Objectives. To evaluate if cumulative weight exposure is associated with weight loss strategy choices and weight loss success. Methods. Data from the National Health and Nutrition Examination Survey were used; a total of 4,562 people age 50 years or older who reported trying to lose weight in the last year were studied. Cumulative weight exposure (CWE) score was defined as the sum of body mass index points above 25 kg/m(2) at the age of 25, 10 years ago, 1 year ago, and now. Weight loss strategies were self-reported and weight loss success was defined as reaching a 5% weight loss in the last year. Results. Chosen strategies for weight loss vary across tertiles of CWE. Participants in the highest CWE tertile were about 4 to 20 times more likely to lose at least 5% of body weight in the past year compared to those in the lowest CWE tertile (P < 0.05). Discussion. Strategies used to lose weight and weight loss success using different weight loss strategies vary considerably across cumulative weight exposure. Thus, cumulative weight exposure might be a variable worth considering when intervening with this population. PMID- 26161268 TI - Plasma Fatty Acids in Zambian Adults with HIV/AIDS: Relation to Dietary Intake and Cardiovascular Risk Factors. AB - Objective. To determine whether 24 hr dietary recalls (DR) are a good measure of polyunsaturated fatty acid (PUFA) intake when compared to plasma levels, and whether plasma PUFA is associated with markers of HIV/AIDS progression and cardiovascular disease (CVD) risk. Methods. In a cross-sectional study among 210 antiretroviral therapy-naive HIV-infected adults from Lusaka, Zambia, we collected data on medical history and dietary intake using 24 hr DR. We measured fatty acids and markers of AIDS progression and CVD risk in fasting plasma collected at baseline. Results. PUFA intakes showed modest correlations with corresponding plasma levels; Spearman correlations were 0.36 (p < 0.01) for eicosapentaenoic acid and 0.21 (p = 0.005) for docosahexaenoic acid. While there were no significant associations (p > 0.05) between total plasma PUFA and C reactive protein (CRP) or lipid levels, plasma arachidonic acid was inversely associated with CRP and triglycerides and positively associated with HDL-C, CD4+ T-cell count, and plasma albumin (p < 0.05). Plasma saturated fatty acids (SFA) were positively associated with CRP (beta = 0.24; 95% CI: 0.08 to 0.40, p = 0.003) and triglycerides (beta = 0.08; 95% CI: 0.03 to 0.12, p < 0.01). Conclusions. Our data suggest that a single DR is inadequate for assessing PUFA intake and that plasma arachidonic acid levels may modulate HIV/AIDS progression and CVD risk. PMID- 26161270 TI - Morbidity and Mortality following Traditional Uvulectomy among Children Presenting to the Muhimbili National Hospital Emergency Department in Dar es Salaam, Tanzania. AB - Background. Traditional uvulectomy is performed as a cultural ritual or purported medical remedy. We describe the associated emergency department (ED) presentations and outcomes. Methods. This was a subgroup analysis of a retrospective review of all pediatric visits to our ED in 2012. Trained abstracters recorded demographics, clinical presentations, and outcomes. Results. Complete data were available for 5540/5774 (96%) visits and 56 (1.0%, 95% CI: 0.7 1.3%) were related to recent uvulectomy, median age 1.3 years (interquartile range: 7 months-2 years) and 30 (54%) were male. Presenting complaints included cough (82%), fever (46%), and hematemesis (38%). Clinical findings included fever (54%), tachypnea (30%), and tachycardia (25%). 35 patients (63%, 95% CI: 49-75%) received intravenous antibiotics, 11 (20%, 95% CI: 10-32%) required blood transfusion, and 3 (5%, 95% CI: 1-15%) had surgical intervention. All were admitted to the hospital and 12 (21%, 95% CI: 12-34%) died. By comparison, 498 (9.1%, 95% CI: 8-10%) of the 5484 children presenting for reasons unrelated to uvulectomy died (p = 0.003). Conclusion. In our cohort, traditional uvulectomy was associated with significant morbidity and mortality. Emergency care providers should advocate for legal and public health interventions to eliminate this dangerous practice. PMID- 26161271 TI - Subjective Visual Vertical during Caloric Stimulation in Healthy Subjects: Implications to Research and Neurorehabilitation. AB - Background. The subjective visual vertical (SVV) is a perception often impaired in patients with neurologic disorders and is considered a sensitive tool to detect otolithic dysfunctions. However, it remains unclear whether the semicircular canals (SCCs) are also involved in the visual vertical perception. Objective. The aim of this study was to analyze the influence of horizontal SCCs on SVV by caloric stimulation in healthy subjects. Methods. SVV was performed before and during the ice-cold caloric stimulation (4 degrees C, right ear) in 30 healthy subjects. Results. The mean SVV tilts before and during the caloric stimulation were 0.31 degrees +/- 0.39 and -0.28 degrees +/- 0.40, respectively. There was no significant difference between the mean SVV tilts before and during stimulation (p = 0.113). Conclusion. These results suggest that horizontal SCCs do not influence SVV. Therefore, investigations and rehabilitation approaches for SVV misperceptions should be focused on otolithic and cognitive strategies. PMID- 26161273 TI - Acute Anterior Myocardial Infarction Accompanied by Acute Inferior Myocardial Infarction: A Very Rare Coronary Artery Anomaly. AB - Coronary artery anomalies are rare and mostly silent in clinical practice. First manifestation of this congenital abnormality can be devastating as syncope, acute coronary syndrome, and sudden cardiac death. Herein we report a case with coronary artery anomaly complicated with ST segment myocardial infarction in both inferior and anterior walls simultaneously diagnosed during primary percutaneous coronary intervention. PMID- 26161272 TI - Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex. AB - Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC) in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28) or P58 on the density of parvalbumin (PV), calbindin (CB), and calretinin (CR) neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6). Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity. PMID- 26161274 TI - A Rare Presentation of Primary Hyperparathyroidism with Concurrent Aldosterone Producing Adrenal Carcinoma. AB - Aldosterone-producing adrenocortical carcinomas are an extremely rare cause of hyperaldosteronism (<1%). Coexistence of different endocrine tumors warrants additional screening for multiple endocrine neoplasia syndromes, especially in young patients with large or malignant masses. We present the case of a 40-year old man with a history of hypertension that presented with an incidental left adrenal tumor during an ultrasound performed for nephrolithiasis. Biochemical assessment showed a mildly elevated calcium (11.1 mg/dL), high parathyroid hormone, and a plasma aldosterone concentration/plasma renin activity ratio of 124.5 (normal < 30), compatible with primary hyperparathyroidism with a concomitant primary hyperaldosteronism. A Tc99m-MIBI scintigraphy showed an abnormally increased tracer uptake in the right superior parathyroid and abdominal computed tomography confirmed a left adrenal tumor of 20 cm. The patient underwent parathyroidectomy and adrenalectomy with final pathology reports of parathyroid hyperplasia and adrenal carcinoma with biochemical remission of both endocrinopathies. He was started on chemotherapy, but the patient developed a frontal cortex and an arm metastasis and finally died less than one year later. PMID- 26161275 TI - Acute Liver Toxicity due to Efavirenz/Emtricitabine/Tenofovir. AB - The fixed-dose combination of Efavirenz/Emtricitabine/Tenofovir is a first-line agent for the treatment of HIV; however few cases have reported hepatotoxicity associated with the drug. We report a case of Efavirenz/Emtricitabine/Tenofovir associated hepatotoxicity presenting mainly with hepatocellular injury characterized by extremely elevated aminotransferase levels, which resolved without acute liver failure or need for liver transplant referral. PMID- 26161276 TI - Severe Osteomyelitis and Septic Arthritis due to Serratia marcescens in an Immunocompetent Patient. AB - Septic arthritis and osteomyelitis due to Serratia marcescens in immunocompetent patients without risk factors are extremely rare. Here, we report a case of septic arthritis and severe adjacent osteomyelitis of the tibia due to Serratia marcescens in a diabetic community-dweller patient. The patient had no contact with healthcare workers or facilities and had no chronic disease except for poorly controlled diabetes. Without predisposing risk factors, this type of infection is extremely rare, even in diabetics. PMID- 26161277 TI - A Case of Spontaneous Tumor Lysis Syndrome in a Patient with Ovarian Cancer. AB - Tumor lysis syndrome (TLS) is a potentially life-threating complication of tumors or chemotherapy treatment. TLS commonly occurs in hematological malignancies, but it is very rare in patients with a solid tumor. In cases of solid tumors, TLS usually occurs spontaneously and after the initiation of anticancer therapy, and it has a high mortality rate. We present the novel case of a 62-year-old woman with an ovarian tumor who spontaneously developed TLS. Surgical reduction of the tumor mass vastly improved her condition. She showed no sign of tumor recurrence 8 months after treatment. As TLS is life-threatening, successful treatments must be seriously considered. PMID- 26161278 TI - Isolated Sensorineural Hearing Loss as a Sequela after Lightning Strike. AB - In most of the surviving patients after a lightning strike, audiovestibular abnormalities have been reported. The most frequently reported type of abnormalities is a tympanic membrane perforation with hearing loss and external ear canal burn. However a sensor neural hearing loss and mixed type hearing loss can also occur, but these occur rarely. A nineteen-year-old female patient had, after a lightning strike, serious burns on the left ear, behind the ear, and on the chest and neck. She also had in her left ear 108 dB hearing loss with irregular central perforation and in her right ear 52 dB sensorineural hearing loss. There was no hearing loss before the strike. A hearing aid was recommended for the right ear and good care and follow-up were recommended for the left ear. A lightning strike can cause serious audiological damage. Therefore, it is necessary to make a careful audiovestibular evaluation of the patients. Although there exist rarely healed cases from sensorineural hearing loss after lightning strike in literature, in our case hearing loss occurred bilaterally and then it healed unilaterally. This condition is quite rare in literature. PMID- 26161279 TI - Alcohol and Substance Use in the Jewish Community: A Pilot Study. AB - Awareness of addictions in the Jewish community is becoming increasingly prevalent, and yet, a gap exists in the literature regarding addictions in this community. Knowledge about the prevalence of addictions within Jewish communities is limited; some believe that Jews cannot be affected by addictions. To address this gap, a pilot study was conducted to gather preliminary evidence relating to addictions and substance use in the Jewish community. Results indicate that a significant portion of the Jewish community knows someone affected by an addiction and that over 20% have a family history of addiction. Future research needs are discussed. PMID- 26161280 TI - Benign Disease of the Stomach. PMID- 26161281 TI - Proximal Gastrectomy for Gastric Cancer. AB - Laparoscopic proximal gastrectomy (LPG) is theoretically a superior choice of minimally-invasive surgery and function-preserving surgery for the treatment of proximal early gastric cancer (EGC) over procedures such as laparoscopic total gastrectomy (LTG), open total gastrectomy (OTG) and open proximal gastrectomy (OPG). However, LPG and OPG are not popular surgical options due to three main concerns: the first, oncological safety; the second, functional benefits; and the third, anastomosis-related late complications (reflux symptoms and anastomotic stricture). Numerous recent studies have concluded that OPG and LPG present similar oncological safety profiles and improved functional benefits when compared with OTG and LTG. While OPG with modified esophagogastrostomy does not provide satisfactory results, OPG with modified esophagojejunostomy showed similar rates of anastomosis-related late complications when compared to OTG. At this stage, no standard reconstruction method post-LPG exists in the clinical setting. We recently showed that LPG with double tract reconstruction (DTR) is a superior choice over LTG for proximal EGC in terms of maintaining body weight and preventing anemia. However, as there is no definitive evidence in favor of LPG with DTR, a randomized clinical trial comparing LPG with DTR to LTG was recommended. This trial, the Korean Laparoscopic Gastrointestinal Surgery Study 05 (NCT01433861), is expected to assist surgeons in choice of surgical approach and strategy for patients with proximal EGC. PMID- 26161282 TI - Treatment Patterns, Costs, and Survival among Medicare-Enrolled Elderly Patients Diagnosed with Advanced Stage Gastric Cancer: Analysis of a Linked Population Based Cancer Registry and Administrative Claims Database. AB - PURPOSE: To assess real-world treatment patterns, health care utilization, costs, and survival among Medicare enrollees with locally advanced/unresectable or metastatic gastric cancer receiving standard first-line chemotherapy. MATERIALS AND METHODS: This was a retrospective analysis of the Surveillance, Epidemiology, and End Results-Medicare linked database (2000~2009). The inclusion criteria were as follows: (1) first diagnosed with locally advanced/unresectable or metastatic gastric cancer between July 1, 2000 and December 31, 2007 (first diagnosis defined the index date); (2) >=65 years of age at index; (3) continuously enrolled in Medicare Part A and B from 6 months before index through the end of follow-up, defined by death or the database end date (December 31, 2009), whichever occurred first; and (4) received first-line treatment with fluoropyrimidine and/or a platinum chemo-therapy agent. RESULTS: In total, 2,583 patients met the inclusion criteria. The mean age at index was 74.8+/-6.0 years. Over 90% of patients died during follow-up, with a median survival of 361 days for the overall post-index period and 167 days for the period after the completion of first-line chemotherapy. The mean total gastric cancer-related cost per patient over the entire post-index follow-up period was United States dollar (USD) 70,808+/-56,620. Following the completion of first-line chemotherapy, patients receiving further cancer-directed treatment had USD 25,216 additional disease-related costs versus patients receiving supportive care only (P<0.001). CONCLUSIONS: The economic burden of advanced gastric cancer is substantial. Extrapolating based on published incidence estimates and staging distributions, the estimated total disease-related lifetime cost to Medicare for the roughly 22,200 patients expected to be diagnosed with this disease in 2014 approaches USD 300 millions. PMID- 26161284 TI - Effects of Continuing Adjuvant S-1 for 1 Year on the Prognosis of Gastric Cancer Patients: Results from a Prospective Single Center Study. AB - PURPOSE: Although several clinical trials have proven the efficacy of adjuvant S 1 treatment in gastric cancers, it is still unclear which patients receive the most benefit. In this study, we prospectively recruited patients with locally advanced gastric cancer who had undergone curative resection followed by adjuvant S-1 administration to investigate which factors affect the outcomes. MATERIALS AND METHODS: Between July 2010 and October 2011, we enrolled 49 patients who underwent curative resection for stage II or III gastric cancer and who subsequently received adjuvant S-1 treatment for 1 year. RESULTS: Twenty-nine patients (59.2%) continued S-1 treatment for 1 year, and 12 patients (24.5%) experienced recurrent disease during the follow-up period. Patients with continuation of S-1 for 1 year had significantly increased rates of disease-free survival (P<0.001) and overall survival (P=0.001) relative to the patients who discontinued S-1 during year 1. Multivariate analysis indicated poor outcomes for patients with stage III disease and those who discontinued S-1 treatment. Excluding patients who discontinued S-1 due to cancer progression (n=7), adjuvant treatment with S-1 still demonstrated a significant difference in the disease free survival rate between the patients who continued treatment and those who discontinued it (P=0.020). CONCLUSIONS: S-1 is tolerated as adjuvant treatment in gastric cancer patients. However, discontinuing S-1 treatment may be an unfavorable factor in the prevention of recurrence. S-1 adjuvant treatment should be continued for 1 year if possible through the proper management of toxicities. PMID- 26161283 TI - Unaided Stapling Technique for Pure Single-Incision Distal Gastrectomy in Early Gastric Cancer: Unaided Delta-Shaped Anastomosis and Uncut Roux-en-Y Anastomosis. AB - PURPOSE: Intracorporeal anastomosis is the most difficult procedure during pure single-incision distal gastrectomy (SIDG) that affects its generalization. We introduced unaided delta-shaped anastomosis (uDelta), a novel anastomosis technique, for gastroduodenostomy after pure SIDG, and compared the results with those of previously reported Roux-en-Y anastomosis (RY). MATERIALS AND METHODS: Between March 2014 and March 2015, SIDG with D1+ lymph node dissection was performed for early gastric cancer through a 2.5-cm transumbilical incision without any additional port. uDelta was performed by the operator alone, without any intracorporeal assistance. RESULTS: uDelta was performed on 11 patents, and uncut RY was performed on 5-patients without open or multiport conversion. R0 resection was performed in all cases. No significant differences were observed in mean age and body mass index between patients who underwent uDelta or RY. Mean operation times were 214.5+/-36.2 minutes for uDelta and 240.8+/-65.9 minutes for RY, which was not significantly different. Reconstruction time for uDelta was shorter than that for RY, with marginal statistical significance (26.1+/-8.3 minutes vs. 38.0+/-9.1 minutes, P=0.05). There were no intraoperative transfusions, 30-day mortality, or anastomosis-related complications in either group. Average length of hospital stay was 8.2+/-1.9 days in the uDelta group and 7.2+/-0.8 days in the RY group (P=0.320). CONCLUSIONS: After carefully considering indications, uDelta can be a feasible and can be a reproducible reconstruction method after SIDG in early gastric cancer. PMID- 26161285 TI - Preoperative Quality of Life in Patients with Gastric Cancer. AB - PURPOSE: We evaluated the socio-personal and clinical factors that can affect preoperative quality of life to determine how to improve preoperative quality of life in patients with gastric cancer. MATERIALS AND METHODS: The preoperative quality of life data of 200 patients (68 females and 132 males; mean age 58.9+/ 12.6 years) with gastric cancer were analyzed according to socio-personal and clinical factors. The Korean versions of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core (QLQ) 30 and the EORTC QLQ-STO22, a gastric cancer-specific module, were used to assess quality of life. Patients were asked to complete the questionnaire preoperatively by themselves. RESULTS: Patients with a higher academic background and stage I disease tended to have higher global health status scores. Highly educated younger men had better physical functioning scores. Highly educated and well nourished patients with stage I cancer had higher role functioning scores. Married patients had better emotional scores. The symptom scales were affected by sex, age, education level, nutrition, and cancer stage. CONCLUSIONS: Preoperative quality of life in patients with gastric cancer can be improved by nutritional support and treatment of symptoms caused by disease progression. Psychological support may be helpful for patients with a poor quality of life. PMID- 26161286 TI - Laparoscopic Partial Fundoplication in Case of Gastroesophageal Reflux Disease Patient with Absent Esophageal Motility. AB - The surgical indications for the treatment of gastroesophageal reflux disease (GERD) in patients with esophageal motility disorders have been debated. We report a case of antireflux surgery performed in a patient with absent esophageal motility as categorized by the Chicago classification (2011). A 54-year-old man underwent laparoscopic Toupet fundoplication due to apparent GERD and desire to discontinue all medications. After surgery, his subjective symptoms improved. Furthermore, objective findings including manometry and 24-hour pH-metry also improved. In our experience, antireflux surgery can improve GERD symptoms patients, even with absent esophageal motility. PMID- 26161287 TI - Solo Intracorporeal Esophagojejunostomy Reconstruction Using a Laparoscopic Scope Holder in Single-Port Laparoscopic Total Gastrectomy for Early Gastric Cancer. AB - Single-incision laparoscopic total gastrectomy for gastric cancer has recently been reported by Seoul National University Bundang Hospital. However, this is not a popular procedure primarily because of the technical difficulties involved in achieving consistent intracorporeal esophagojejunostomy. At Seoul National University Bundang Hospital, we recently introduced a simple, easy-to-use, low profile laparoscopic manual scope holder that enables the maintenance of a stable field of view, the most demanding condition in single-port gastrectomy. In this technical report, we describe in detail the world's first solo single-incision laparoscopic total gastrectomy with D1+ lymph node dissection and intracorporeal esophagojejunostomy for proximal early gastric cancer. PMID- 26161288 TI - Metachronous Liver Metastasis Resulting from Early Gastric Carcinoma after Subtotal Gastrectomy Following Endoscopic Resection: A Case Report. AB - Hepatic metastasis of early gastric cancer (EGC) following subtotal gastrectomy with lymphadenectomy is rare. We report the case of a 61-year-old male patient who was diagnosed with EGC that was initially treated using endoscopic submucosal dissection (ESD) and subsequently underwent laparoscopic subtotal gastrectomy. Histopathological examination of the patient's ESD specimen showed a moderately differentiated tubular adenocarcinoma invading the submucosa without lymphatic invasion. The deep margin of the specimen was positive for adenocarcinoma, and he subsequently underwent laparoscopic distal gastrectomy. The patient developed liver metastasis 15 months after the operation and then underwent liver resection. Histology of the resected specimen confirmed the diagnosis of two foci of metastatic adenocarcinoma originating from stomach cancer. Immunohistochemical analysis of the specimen demonstrated overexpression of human epidermal growth factor receptor 2. The patient was treated with trastuzumab in combination with chemotherapy consisting of capecitabine and cisplatin. Twenty-four months after the operation, the patient remained free of recurrence. PMID- 26161289 TI - A Surgically Resected Large Sarcomatoid Carcinoma of the Jejunum: A Case Report and Literature Review. AB - Sarcomatoid carcinoma of the small intestine is rare, and only 30 cases have been reported to date. This disease generally exhibits a very poor prognosis. Here we report the case of a 67-year-old man with a sarcomatoid carcinoma in the jejunum, who was hospitalized for diarrhea, fever, nausea, and vomiting. The tumor was located at the jejunum and had a large round shape with geographic necrosis. It involved the entire wall of the small intestine and had directly invaded the neighboring sigmoid colon. Both lobes of the liver had multiple metastases. The patient underwent surgical resection of the jejunum. On immunohistochemical analysis, the tumor was positive for epithelial and mesenchymal markers. The patient died from rapid progression of the liver metastases 6 weeks after the surgery. PMID- 26161290 TI - Chronic Gastric Volvulus with Laparoscopic Gastropexy after Endoscopic Reduction: A Case Report. AB - Gastric volvulus is an uncommon clinical entity. There are three types of gastric volvulus; organoaxial, mesenteroaxial and combined type. This condition can lead to a closed-loop obstruction or strangulation. Traditional surgical therapy for gastric volvulus is based on an open approach. Here we report a successful case of a patient with chronic gastric volvulus with a laparoscopic treatment. A 79 year-old woman came to the emergency department with epigastric pain accompanied by nausea for 2 weeks. Abdominal computed tomography revealed markedly distended stomach with transposition of gastroesophageal Junction and gastric antrum. Barium meal study revealed presence of the antrum was folded over 180 degrees that was located above gastroesophageal junction. We attempted an endoscopic reduction, but it was unsuccessful. The patient got laparoscopic anterior gastropexy. Based on our result, laparoscopic gastropexy can be considered as a good choice of the treatment for gastric volvulus. PMID- 26161291 TI - Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system. PMID- 26161292 TI - THz and mm-Wave Sensing of Corneal Tissue Water Content: In Vivo Sensing and Imaging Results. AB - A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo. These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10-15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10* higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo. PMID- 26161293 TI - Loss of Sarcomere-associated Formins Disrupts Z-line Organization, but does not Prevent Thin Filament Assembly in Caenorhabditis elegans Muscle. AB - Members of the formin family of actin filament nucleation factors have been implicated in sarcomere formation, but precisely how these proteins affect sarcomere structure remains poorly understood. Of six formins in the simple nematode Caenorhabditis elegans, only FHOD-1 and CYK-1 contribute to sarcomere assembly in the worm's obliquely striated body-wall muscles. We analyze here the ultrastructure of body-wall muscle sarcomeres in worms with putative null fhod-1 and cyk-1 gene mutations. Contrary to a simple model that formins nucleate actin for thin filament assembly, formin mutant sarcomeres contain thin filaments. Rather, formin mutant sarcomeres are narrower and have deformed thin filament anchoring Z-line structures. Thus, formins affect multiple aspects of sarcomere structure. PMID- 26161294 TI - Effects of Peginesatide Injection on QTc Interval in Healthy Adults. AB - A single-dose, randomized, double-blind, placebo- and positive-controlled, three period crossover study was conducted to evaluate the effect of peginesatide injection on QT interval in healthy adults. Subjects received single doses of placebo, peginesatide injection 0.1 mg/kg intravenous, or moxifloxacin 400 mg during three treatment periods, separated by 14-day washout intervals. ECG recordings and blood samples for peginesatide and moxifloxacin plasma concentrations were collected prior to dosing and through 22 hours postdose. QT intervals were measured with a high resolution manual on-screen caliper method. The study endpoint was the mean difference between peginesatide and placebo in baseline-adjusted corrected QT interval (ddQTc). The maximum upper bound of the one-sided 95% CI was 2.2 milliseconds at 0.75 hours for Fridericia-corrected ddQTc (ddQTcF) and 2.2 milliseconds at 0.25 hours for individual corrected ddQTcI. The linear relationship between ddQTcF and peginesatide concentrations was essentially flat and not statistically significant [slope = 0.001, P = 0.126, 90% CI: (<-0.0005, 0.002)]. Using this model, the projected ddQTcF effect at the observed mean peak plasma concentration is estimated to be 0.9 milliseconds, 90% CI: (-2.0, 0.3 milliseconds). There were no peginesatide-related effects on heart rate, PR interval, or QRS interval. Thus, there is no anticipated cardiovascular effect of peginesatide injection 0.1 mg/kg in patients. PMID- 26161295 TI - In Vitro Anticancer Activity of the Crude Extract and two Dicinnamate Isolates from the Jamaican Ball Moss (Tillandsia Recurvata L.). AB - A crude chloroform extract from the Jamaican Ball Moss (Tillandsia recurvata L.) was tested for activity against three human cancer cell lines including; A375 (human melanoma), MCF-7 (human breast) and PC-3 (human prostate cancer) using the WST-1 assay. IC50s obtained against these cell lines; A375, MCF-7 and PC-3 in the presence of the crude extract are; 0.9MUg/ml, 40.51MUg/ml and 5.97MUg/ml respectively indicating the promising anti-cancer activity of the ball moss extract. Further, preliminary phytochemical study was conducted in an attempt to identify and isolate the phytochemicals that could possibly be responsible for the observed bioactivity of the ball moss chloroform extract. As a result, two dicinnamates were isolated; 1,3-di-O-Cinnamoyl-glycerol (1) and (E)-3 (cinnamoyloxy)-2-hydroxypropyl 3-(3,4-dimethoxyphenyl)acrylate (2) and we report for the first time isolation of compound 2. Even though the bioactivity of these two islaotes were fairly weak against the cell lines, the results presented here will prove useful for further research aimed at identifying molecules that maybe effective against melanoma, breast and prostate cancers associated with fewer side-effects. PMID- 26161296 TI - Melanoma tumor growth is accelerated in a mouse model of sickle cell disease. AB - BACKGROUND: The effect of sickle cell disease (SCD) on tumor growth is unknown. Sickled red blood cells may form aggregates within the microvasculature of hypoxic tumors and reduce blood flow leading to impairment of tumor growth. However, there is a paucity of data related to tumor growth in SCD. METHODS: To investigate the effect of SCD on tumor growth in a melanoma model, we generated SCD and control mice using bone marrow transplantation and inoculated the chest wall with B16-F10 melanoma cells. Tumor growth was monitored and angiogenesis was studied in vivo and in vitro. RESULTS: From day 1 to 21, tumor growth rate was nearly identical between SCD and WT mice, however from day 22 to day 29 tumor growth was accelerated in SCD mice compared to WT mice. Disparity in tumor size was confirmed at autopsy with an approximate 2-fold increase in tumor weights from SCD mice. Tumors from SCD mice showed increased vascularity and elevated levels of heme oxygenase-1 (HO-1). HO-1 inhibition with zinc protoporphyrin (ZnPP) blocked the angiogenic and tumor growth response to SCD in vivo and the response to hemin in vitro. CONCLUSIONS: Growth of melanoma tumors is potentiated in a mouse model of SCD. Therapies targeting angiogenesis or HO-1 may be useful in SCD patients with malignant tumors. PMID- 26161297 TI - Circulating DNA and Micro-RNA in Patients with Pancreatic Cancer. AB - Collecting repeat samples of blood ("liquid biopsies") is a broadly used clinical approach for serial monitoring of disease or response to treatments. In patients with cancer the most distinct molecular feature are somatic mutations acquired by cancer cells present in the diseased tissue. Indeed, mutant DNA derived from dying or lysed cancer cells can be isolated from patient serum samples, subjected to DNA sequencing and to analysis of abundance as a measure of tumor burden. Also, changes in the DNA mutation patterns in serum samples collected over time can indicate altered pathways or clonal evolution of the disease and altered abundance of mutant DNA suggests an altered disease burden. In addition, during the course of treatment, changes in circulating DNA mutation patterns can indicate the emergence of resistant clones and prompt changes in treatment. In contrast to mutant DNA, microRNAs (miR) are transcribed, processed, packaged and released from cells in normal and in diseased tissues as part of the extracellular crosstalk between cells. Interestingly, released miR can function in cell-to-cell communication and as hormone-like signals that operate at a distance through their release into the circulation and subsequent uptake into cells in distant tissues. Circulating miR expression patterns can be established from serial serum samples and monitored for alterations over time. Circulating miR provide a readout of the organism's steady state and serial analyses will indicate changes in the response to therapy or an altered physiologic or disease state. Furthermore, changes in circulating miR patterns can indicate treatment efficacy or resistance as well as adverse effects associated with the respective intervention. Thus, the combined serial analysis of mutant DNA and miR in the circulation has the potential to provide a molecular footprint of pancreatic cancer and can be used to monitor treatment responses or resistance to treatment in real time with a minimally invasive procedure. PMID- 26161298 TI - Antimetabolite Treatment for Pancreatic Cancer. AB - Pancreatic cancer is a deadly and aggressive disease. Less than 1% of diagnosed patients survive 5 years with an average survival time of only 4-8 months. The only option for metastatic pancreatic cancer is chemotherapy where only the antimetabolites gemcitabine and 5-fluorouracil are used clinically. Unfortunately, efforts to improve chemotherapy regimens by combining, 5 fluorouracil or gemcitabine with other drugs, such as cisplatin or oxaliplatin, have not increased cell killing or improved patient survival. The novel antimetabolite zebularine shows promise, inducing apoptosis and arresting cellular growth in various pancreatic cancer cell lines. However, resistance to these antimetabolites remains a problem highlighting the need to discover and develop new antimetabolites that will improve a patient's overall survival. PMID- 26161299 TI - Applications of Raman micro-spectroscopy to stem cell technology: label-free molecular discrimination and monitoring cell differentiation. AB - Stem cell therapy is widely acknowledged as a key medical technology of the 21st century which may provide treatments for many currently incurable diseases. These cells have an enormous potential for cell replacement therapies to cure diseases such as Parkinson's disease, diabetes and cardiovascular disorders, as well as in tissue engineering as a reliable cell source for providing grafts to replace and repair diseased tissues. Nevertheless, the progress in this field has been difficult in part because of lack of techniques that can measure non-invasively the molecular properties of cells. Such repeated measurements can be used to evaluate the culture conditions during differentiation, cell quality and phenotype heterogeneity of stem cell progeny. Raman spectroscopy is an optical technique based on inelastic scattering of laser photons by molecular vibrations of cellular molecules and can be used to provide chemical fingerprints of cells or organelles without fixation, lysis or use of labels and other contrast enhancing chemicals. Because differentiated cells are specialized to perform specific functions, these cells produce specific biochemicals that can be detected by Raman micro-spectroscopy. This mini-review paper describes applications of Raman micro-scpectroscopy to measure moleculare properties of stem cells during differentiation in-vitro. The paper focuses on time- and spatially-resolved Raman spectral measurements that allow repeated investigation of live stem cells in-vitro. PMID- 26161300 TI - High-Performance Flexible Bottom-Gate Organic Field-Effect Transistors with Gravure Printed Thin Organic Dielectric. PMID- 26161301 TI - Preliminary in vitro evaluation of genistein chemopreventive capacity as a result of esterification and cyclodextrin encapsulation. AB - The present study focuses on the synthesis and analysis of a genistein ester derivative with myristic acid followed by beta cyclodextrin encapsulation; physicochemical analysis using consecrated techniques such as FTIR, MS, DSC, and SEM revealed both a successful esterification and inclusion inside the cyclodextrin cavity. Cytotoxic effects were measured in vitro on three human cell lines: HeLa (cervix adenocarcinoma), A2780 (ovary carcinoma), and A431 (skin epidermoid carcinoma). The in vitro biological analysis exhibited rather poor antiproliferative results on all three tested cancer cell lines, behavior that may be due to the high stability of the complex within the in vitro environment. PMID- 26161302 TI - Immunohistochemical expression of CXCR4 on breast cancer and its clinical significance. AB - Many tumor cells express chemokines and chemokine receptors, and, for this reason, these molecules can affect the tumor progression. It is known that breast cancer is a complex and heterogeneous neoplasia comprising distinct diseases, histological characteristics, and clinical outcomes. The most studied role for CXCL12 chemokine and its receptor CXCR4 in breast cancer pathogenesis is the metastasis event, although several reports have demonstrated its involvement in other processes, such as angiogenesis and tumor growth. It has been found that CXCR4 is required for breast cancer cell migration to other sites such as lung, bone, and lymph nodes, which express high levels of CXCL12 chemokine. Therefore, CXCR4 is being considered a prognostic marker in breast cancer. Within this context, this review summarizes established studies involving expression of CXCR4 on breast cancer, focusing on its clinical significance. PMID- 26161303 TI - Physiological functions and clinical implications of fibrinogen-like 2: A review. AB - Fibrinogen-like 2 (FGL2) encompasses a transmembrane (mFGL2) and a soluble (sFGL2) form with differential tertiary structure and biological activities. Typically, mFGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas sFGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain (FRED). The FRED of FGL2 confers specificity and complexity in the action of FGL2, including receptor recognition, calcium affiliation, and substrate binding. Constitutive expression of FGL2 during embryogenesis and in mature tissues suggests FGL2 might be physiologically important. However, excessive induction of FGL2 under certain medical conditions (e.g., pathogen invasion) could trigger complement activation, inflammatory response, cellular apoptosis, and immune dysfunctions. On the other hand, complete absence of FGL2 is also detrimental as lack of FGL2 can cause autoimmune glomerulonephritis and acute cellular rejection of xenografts. All these roles involve mFGL2, sFGL2, or their combination. Although it is not clear how mFGL2 is cleaved off its host cells and secreted into the blood, circulating sFGL2 has been found correlated with disease severity and viral loading among patients with human hepatitis B virus or hepatitis C virus infection. Further studies are warranted to understand how FGL2 expression is regulated under physiological and pathological conditions. Even more interesting is to determine whether mFGL2 can fulfill an immunoregulatory role through its FRED at carboxyl end of the molecule and, and vice versa, whether sFGL2 is procoagulant upon binding to a target cell. Knowledge in this area should shed light on development of sFGL2 as an alternative immunosuppressive agent for organ transplantation or as a biomarker for predicting disease progression, monitoring therapeutic effects, and targeting FGL2 for repression in ameliorating fulminant viral hepatitis. PMID- 26161304 TI - Current opinions on indications and algorithms for acellular dermal matrix use in primary prosthetic breast reconstruction. AB - Acellular dermal matrix (ADM) is widely used in primary prosthetic breast reconstruction. Many indications and contraindications to use ADM have been reported in the literature, and their use varies by institution and surgeon. Developing rational, tested algorithms to determine when ADM is appropriate can significantly improve surgical outcomes and reduce costs associated with ADM use. We review the important indications and contraindications, and discuss the algorithms that have been put forth so far. Further research into algorithmic decision-making for ADM use will allow optimized balancing of cost with risk and benefit. PMID- 26161305 TI - Current strategies with 2-staged prosthetic breast reconstruction. AB - Over the last decade, prosthetic-based breast reconstruction has been revolutionized with technological advancements. Reconstructive surgeons now have a multitude of prosthetic devices and tissue expanders, tools for intraoperative perfusion analysis, implantable bioprosthetic materials and a technique for autoaugmentation within their armamentarium to reconstruct natural breasts today like never before. PMID- 26161306 TI - Abdominal perforator vs. muscle sparing flaps for breast reconstruction. AB - Abdominally based free flaps have become the mainstay for women that desire to use their own tissue as a means of breast reconstruction after mastectomy. As the techniques have evolved, significant effort has been invested in finding the best means of minimizing morbidity to the abdominal donor site while ensuring a viable reconstructed breast that is aesthetically pleasing. This manuscript reviews and compares the muscle sparing free transverse rectus abdominis myocutaneous (MsfTRAM), the deep inferior epigastric artery perforator (DIEP), and the superficial inferior epigastric artery (SIEA) flaps, regarding flap success rate, operative times, abdominal donor site morbidity and residual functionality, hospital lengths of stay and associated costs, impact of co-morbid conditions, and resilience after adjuvant radiation treatment. PMID- 26161307 TI - Current perspectives on radiation therapy in autologous and prosthetic breast reconstruction. AB - BACKGROUND: Postmastectomy radiation therapy (PMRT) has a well-established deleterious effect on both prosthetic and autologous breast reconstruction. The purpose of this study was to perform a literature review of the effects of PMRT on breast reconstruction and to determine predictive or protective factors for complications. METHODS: The MEDLINE and EMBASE databases were reviewed for articles published between January 2008 and January 2015 including the keywords "breast reconstruction" and "radiation therapy" to identify manuscripts focused on the effects of radiation on both prosthetic and autologous breast reconstruction. This subgroup of articles was reviewed in detail. RESULTS: Three hundred and twenty articles were identified and 43 papers underwent full text review. The 16 papers provided level III evidence; 10 manuscripts provided level I or II evidence. Seventeen case series provided level IV evidence and were included because they presented novel perspectives. The majority of studies focused on the injurious effects of radiation therapy and increased complications and concomitant lower patient satisfaction. CONCLUSIONS: Prosthetic based breast reconstruction and immediate autologous reconstruction are associated with lower patient satisfaction in the setting of radiation therapy. Autologous reconstructions can improve patient satisfaction as well as lower revision surgery and long term complications when performed in a delayed fashion after PMRT. PMID- 26161308 TI - Fat grafting and breast reconstruction: tips for ensuring predictability. AB - Autologous fat grafting is widely used in breast surgery to refine and optimize aesthetic outcomes. Despite its widespread use, obtaining predictable, reliable, and consistent outcomes remains a significant challenge and is influenced by the technique used for procurement, processing, and placement of the fat. At present, there is no published consensus on the optimal technique. The purpose of this article is to review current techniques at each stage of fat grafting and provide tips on best practices based on the published literature as well as our extensive clinical experience. PMID- 26161310 TI - The biplanar oncoplastic technique case series: a 2-year review. AB - BACKGROUND: Oncoplastic techniques for breast reconstruction following partial mastectomy are now commonly included in the armamentarium of most reconstructive plastic surgeons. These techniques have been frequently used for women with large breast volume and less frequently used form women with small to moderate breast volume. Most women with smaller breast volumes have been typically considered for mastectomy. As an alternative to mastectomy, the biplanar technique was designed and described as an oncoplastic option. The purpose of this manuscript is to review our 2-year experience using this technique in a series of women with small to moderate breast volume. METHODS: A retrospective review of patients who underwent oncoplastic surgery from 2011-2012 by the senior authors (RM and MYN) was completed. Ten patients were identified that had the biplanar technique involving glandular tissue rearrangement in conjunction with the immediate placement of a submuscular implant or tissue expander. Patient demographics, perioperative details, and post-operative outcomes were evaluated. RESULTS: The mean age and BMI of the ten patients in the study was 56 years (range, 40-68 years) and 24.1 years (range, 20.3-28.6 years) respectively. The mean resection volume was 76.5 g (range, 25-164 g). Eight patients had placement of a permanent implant and two patients had placement of a tissue expander. The average volume of the implanted devices was 138 cc (range, 90-300 cc). In eight patients, a sheet of acellular dermal matrix was used. Immediate biplanar reconstruction was performed in seven patients and a staged-immediate biplanar reconstruction was performed in three patients. Complications included a positive margin on final pathology requiring mastectomy (n=1), infection (n=1), incisional dehiscence following radiation (n=1), and loss of nipple sensation (n=2). Follow-up ranged from 4.5-27 months (mean of 19.5 months). CONCLUSIONS: The biplanar oncoplastic technique may represent a valuable option in women with small to moderate breast volumes that choose to have breast conservation therapy (BCT). This technique has demonstrated success with minimizing contour irregularities and maintaining breast volume. Based on our early experience, patient satisfaction is favorable. PMID- 26161309 TI - Lymphatic mapping and lymphedema surgery in the breast cancer patient. AB - Upper limb lymphedema can be an unfortunate sequela following the oncologic treatment of breast cancer. The surgical treatment of lymphedema has had a recent renewed clinical interest paralleling innovative descriptions of surgical techniques and imaging modalities. In addition, an improved understanding of the physiology and pathophysiology of lymphedema has allowed improved translation to the clinical condition. Various surgical options exist to decrease the symptom burden of upper limb lymphedema, including vascularized lymph node (VLN) transfer, lymphovenous bypass (LVB), liposuction, lymphatic grafting, and excisional procedures. Modern imaging techniques help to improve the consistency and accuracy of these surgical treatment options. A multi-modal treatment plan utilizing non-operative and surgical therapies has the potential to improve various factors related to overall patient quality of life. This review details all of the current operative treatment strategies and modern imaging modalities used in the treatment of lymphedema. PMID- 26161311 TI - Oncoplastic volume replacement technique for the upper inner quadrant using the omental flap. AB - BACKGROUND: In breast-conserving surgery (BCS), a large defects in the upper inner quadrant (UIQ) named the no man's land of the breast will cause shift the nipple in an unnatural upward or medial fashion. We have developed oncoplastic volume replacement techniques using a laparoscopically harvested omental flap (OF). This paper presents our experiences performing partial breast reconstruction for the defect in the UIQ using the OF. METHODS: A wide excision (>20% of the breast tissue) was performed mainly through a periareolar incision. The pedicled OF was harvested laparoscopically. A small incision was made along the medical inframammary fold and a subcutaneous tunnel was created towards the xyphoid process. The OF was extracted through the tunnel, and used to fill the defect in the UIQ. RESULTS: Thirty patients were included in this study. The median resected breast volume was 142 g. A donor-site complication was only one ventral hernia. The surgical margins were positive in one patient (3.3%), and neither local nor systemic recurrence has occurred during medial follow-up periods of 64 months. Cosmetic outcomes were mostly satisfactory with negligible donor-site scars, and more than 80% of the patients scored excellent or good. CONCLUSIONS: The OF is a useful volume replacement technique for the UIQ which is the most difficult quadrant for the other distant flaps. PMID- 26161312 TI - Use of latissimus dorsi muscle onlay patch alternative to acellular dermal matrix in implant-based breast reconstruction. AB - BACKGROUND: An acellular dermal matrix (ADM) is applied to release the surrounding muscles and prevent dislocation or rippling of the implant. We compared implant-based breast reconstruction using the latissimus dorsi (LD) muscle, referred to as an "LD muscle onlay patch," with using an ADM. METHOD: A total of 56 patients (60 breasts) underwent nipple sparing mastectomy with implant-based breast reconstruction using an ADM or LD muscle onlay patch. Cosmetic outcomes were assessed 4 weeks after chemotherapy or radiotherapy, and statistical analyses were performed. RESULTS: Mean surgical time and hospital stay were significantly longer in the LD muscle onlay patch group than the ADM group. However, there were no statistically significant differences between groups in postoperative complications. Cosmetic outcomes for breast symmetry and shape were higher in the LD muscle onlay patch group. CONCLUSIONS: Implant-based breast reconstruction with an LD muscle onlay patch would be a feasible alternative to using an ADM. PMID- 26161313 TI - Endotracheal Tube Cuff Pressure Assessment: Education May Improve but not Guarantee the Safety of Palpation Technique. AB - BACKGROUND: Endotracheal Tube Cuff Pressure (ETCP) should be kept in the range of 20 - 30 cm H2O. Earlier studies suggested that ETCP assessment by palpation of pilot balloon results in overinflation or underinflation and subsequent complications such as tracheal wall damage and aspiration. OBJECTIVES: The current study aimed to evaluate the effect of an in vitro educational program on the ability of anesthesia personnel to inflate Endotracheal Tube Cuffs (ETT) within safe pressure limits. PATIENTS AND METHODS: The survey included two series of blinded ETCP measurements in intubated patients before and two weeks after an in vitro educational intervention. The in vitro educational program included two separate trials. The anesthesia personnel were asked to inflate an ETT cuff inserted in a tracheal model using their usual inflation technique. In the same session, six ETTs at different pressure levels were examined by the participants and their estimation of ETCP was recorded. After the in vitro assessment, the participants were informed about the actual pressure of the in vitro ETCPs and were allowed to train their fingers by in vitro pilot balloon palpation with validated manometer measurements. RESULTS: The mean ETCP after the in vitro survey was significantly lower than the mean ETCP before the intervention (45 +/- 13 vs. 51 +/- 15 cm H2O, P = 0.002). The rate of measurements within the safe pressure limits significantly improved after the in vitro education (24.2% vs. 39.7%, P = 0.002). CONCLUSIONS: Implementing educational programs with the introduction of estimation techniques besides the use of manometer as a standard intraoperative monitoring will improve the safety of the practice. PMID- 26161314 TI - The Effect of Adding Sufentanil to 0.5% Hyperbaric Bupivacaine on Duration of Brachial Plexus Blockade in Chronic Opium Abusers: a Randomized Clinical Trial. AB - BACKGROUND: Anesthesia induction in patients with current substance abuse can be a challenge for anesthesiologists. OBJECTIVES: This study aimed to evaluate the effect of adding Sufentanil to Bupivacaine on duration of brachial plexus nerve block. PATIENTS AND METHODS: One hundred and twenty patients with (Groups C and D) and without (Groups A and B) a history of opium abuse (60 in each group) scheduled for elective upper extremity procedures were randomly assigned to either receive 30 mL bupivacaine alone (Groups A and C) or in combination with additional 10 ug sufentanil (Groups B and D). An ultrasound-guided technique was applied to perform upper extremity brachial plexus blockade. The onset and duration of sensory and motor blocks were recorded and compared between the four groups. RESULTS: The duration of sensory and motor block were significantly less in Group C (537.0 +/- 40.1 minutes, 479.0 +/- 34.8 minutes) and the longest duration of sensory and motor block was observed in group B (705.0 +/- 43.8 minutes, 640.0 +/- 32.5 minutes). The duration of sensory and motor block in Group B (705.0 +/- 43.8 minutes, 640.0 +/- 32.5 minutes) was longer and statistically higher than group A (619.5 +/- 48.0 minutes, 573.2 +/- 31.5 minutes), the same trend was observed in group D (598.6 +/- 53.2 minutes, 569.3 +/- 39.9 minutes) over group C (537.0 +/- 40.1 minutes, 479.0 +/- 34.8 minutes) (P < 0.001, one-way ANOVA). CONCLUSIONS: The length of sensory and motor blockade is shorter in chronic opioid abusers. Adding 10 ug sufentanil to hyperbaric bupivacaine in opium abusers lengthened the sensory and motor block duration. PMID- 26161315 TI - Benson Relaxation Technique in Reducing Pain Intensity in Women After Cesarean Section. AB - BACKGROUND: Post-cesarean section women experience pain due to operative trauma. Pain sensation can be reduced by pain management. Pharmacological and non pharmacological treatments can be used. The Benson Relaxation Technique is a non pharmacological way suitable to reduce pain, but there are limited studies on its post-cesarean section use. OBJECTIVES: This study aimed to determine the effect of Benson Relaxation Technique in reducing pain intensity in women after cesarean section. PATIENTS AND METHODS: This was a quasi-experiment study with pre and post-test design. A prospective, not blind, randomized assign, two groups parallel study was conducted in Cibabat hospital Cimahi as intervention group (IG) and Sartika Asih hospital as control group (CG). Post cesarean section women with quota sampling who met the inclusion criteria were consecutively assigned to either experimental (n = 30) or control group (n = 30). Women in the experimental group received the Benson relaxation technique and those in the control group received regular care from the health workers. The outcome pain severity was measured by visual analogue scale. Those instruments were applied before and after intervention. RESULTS: The mean of pain score before intervention at CG was 4.43 cm. It was decreased to 4.40 cm (1 min), 4.27 cm (12 h), 4.10 cm (24 h), 4.00 cm (36 h), 3.93 cm (48 h), 3.83 cm (60 h), 3.67 cm (72 h) and 3.51 cm (84 h). Meanwhile, the IG was 4.97 cm. It was decreased to 4.90 cm (1 min), 4.23 cm (12 h), 3.57 cm (24 h), 3.03 cm (36 h), 2.77 cm (48 h), 2.73 cm (60 h), 2.67 cm (72 h) and 2.63 cm (84 h). The study found a significant difference comparing pain intensity before and after the intervention in CG and IG (P = 0.001), but pain reduced in IG more than CG. CONCLUSIONS: The Benson relaxation could reduce pain intensity in women after cesarean section. PMID- 26161316 TI - Magnesium and Ketamine Gargle and Postoperative Sore Throat. AB - BACKGROUND: Postoperative sore throat is one of the most common complications after endotracheal intubation. Both Ketamine and magnesium can block N-methyl-D aspartic acid (NMDA) receptors and provide central and local analgesia. OBJECTIVES: To compare the effect of magnesium sulfate and ketamine gargle on the incidence and severity of postoperative sore throat. PATIENTS AND METHODS: A total of 100 patients candidate for emergency acute appendicitis surgery were enrolled in the study. Patients in ketamine group received ketamine gargle (0.5 mg/kg) and magnesium group received magnesium sulfate gargle (20 mg/kg up to 30 mL dextrose water 20%) 15 minutes before the operation. Patient complaint of postoperative sore throat, and its severity measured by visual analogue scale (VAS) were recorded at baseline in recovery room, and then 2, 4, and 24 hours after operation. RESULTS: There were no significant differences between age, sex, and body mass index (BMI) between two groups of patients. Hemodynamics of patients, including blood pressure, respiratory rate, oxygen saturation %, and conscious state were not significantly different (P > 0.05). Number of patients with sore throat were significantly lower in magnesium group compared to ketamine group at 2 (P = 0.032), 4 (P = 0.02), and 24 hours (P = 0.01) after the operation. Sore throat pain score (VAS) was significantly lower in magnesium group compared to ketamine group at 2 (P = 0.019), 4 (P = 0.028), and 24 hours (P = 0.014) after the operation. CONCLUSIONS: Magnesium at low dose decreases sore throat and pain severity more effectively compared to ketamine gargle. PMID- 26161317 TI - Intrarectal Lidocaine-Diltiazem-Meperidine Gel for Transrectal Ultrasound Guided Prostate Biopsy. AB - BACKGROUND: TRUS-guided needle biopsy of the prostate gland is the current standard method used for diagnosis of prostate cancer. Pain control during this procedure is through the use of i.v. sedation or local anaesthetic (LA), depending on clinician preference. OBJECTIVES: The aim of this study was to evaluate the effectiveness of intrarectal lidocaine, lidocaine-diltiazem and lidocaine-meperidine-diltiazem gel for anesthetizing transrectal ultrasound guided prostate biopsy. PATIENTS AND METHODS: In a randomized double-blind clinical trial, 100 consecutive patients were divided into three groups. The patients received one of the gels before transrectal ultrasound guided prostate needle biopsy: group A, intrarectal and perianal lidocaine, gel 1 g; group B, intrarectal lidocaine gel, 1 g, + perianal diltiazem, 1 g; group C, intrarectal lidocaine gel, 1 g, + meperidine, 25 mg, and perianal diltiazem, 1 g. Visual analog pain scale was used to estimate pain during probe insertion and biopsy. Heart rate and blood pressure during probe insertion and biopsy were recorded too. RESULTS: The mean of visual analog pain scale was 4.5 in group A, 3.5 in group B, and 2.0 in group C during probe insertion (P value = 0.01). The mean of visual analog pain scale was 5.1 in group A, 3.5 group B, and 2.5 in group C during biopsy (P value = 0.001). The groups were comparable for patients' age, weight, serum prostate-specific antigen (PSA), and prostate size (P > 0.05). No side effects of meperidine and lidocaine including drowsiness, dizziness, tinnitus and light-headedness or requiring assistance for activity were noted. CONCLUSIONS: Lidocaine-meperidine-diltiazem gel provides significantly better pain control than lidocaine-diltiazem gel and lidocaine gel alone during transrectal ultrasound guided prostate biopsy and probe insertion. This mixture gel is safe, easy to administer and well accepted by patients. PMID- 26161318 TI - Pressure Monitoring of Intraneural an Perineural Injections Into the Median, Radial, and Ulnar Nerves; Lessons From a Cadaveric Study. AB - BACKGROUND: Nerve damage after regional anesthesia has been of great concern to anesthetists. Various modalities have been suggested to recognize and prevent its incidence. An understudied area is the measurement of intraneural pressure during peripheral nerve blockade. Previous investigations have produced contradicting results with only one study being conducted on human cadavers. OBJECTIVES: The purpose of this investigation was to systematically record intraneural and perineural injection pressures on the median, ulnar, and radial nerves exclusively as a primary outcome. MATERIALS AND METHODS: Ultrasonography-guided injections of 1 mL of 0.9% NaCl over ten seconds were performed on phenol glycerine embalmed cadaveric median, ulnar, and radial nerves. A total of 60 injections were performed, 30 intraneural and 30 perineural injections. The injections pressure was measured using a controlled disc stimulation device. Anatomic dissection was used to confirm needle placement. RESULTS: Intraneural needle placement produced significantly greater pressures than perineural injections did. The mean generated pressures in median, radial, and ulnar nerves were respectively 29.4 +/- 9.3, 27.3 +/- 8.5, and 17.9 +/- 7.0 pound per square inch (psi) (1 psi = 51.7 mmHg) for the intraneural injections and respectively 7.2 +/- 2.5, 8.3 +/- 2.5, and 6.7 +/- 1.8 psi for perineural injections. Additionally the intraneural injection pressures of the ulnar nerve were lower than those of the median and radial nerves. CONCLUSIONS: Obtained results demonstrate significant differences between intraneural and perineural injection pressures in the median, ulnar, and radial nerves. Intraneural injection pressures show low specificity but high sensitivity suggesting that pressure monitoring might be a valuable tool in improving the safety and efficacy of peripheral nerve blockade in regional anesthesia. Peripheral nerves "pressure mapping" hypothetically might show difference amongst various nerves depending on anatomic location, histologic structure, and ultrasonographic appearance. PMID- 26161319 TI - Intra - operative Anesthesia Management in Patients Undergoing Surgical Irreversible Electroporation of the Pancreas, Liver, Kidney, and Retroperitoneal Tumors. AB - BACKGROUND: Irreversible electroporation (IRE) is a relatively new approach to the management of multiple types of locally advanced soft tissue tumors. Unique peri-procedural anesthetic management is needed in the safe and effective delivery of this therapy. OBJECTIVES: This study analyzed IRE therapy in relation to anesthetic management for our initial cohort and then established and validated a set of best practical guidelines for general anesthesia in patients undergoing IRE for abdominal tumors. PATIENTS AND METHODS: An IRB-approved prospective data collection outcome protocol was utilized. This study was broken up into two cohorts as follows: the initial 38 patients (pts) undergoing IRE in which anesthetic management was not defined or optimized and then a 40-pt validation cohort to establish the most efficacious anesthetic protocols. RESULTS: During IRE delivery, a deeper neuromuscular blockade is required to ensure that all retroperitoneal muscle excitation was minimized. In the initial 38-pt cohort, attempts to treat hypertension (median SBP 190, range 185-215 and median diastolic 98, range 91-115) were made with various types of anti hypertensives with minimal-to-insufficient effects. The established inhalation was sevoflurane with an approximate median dose of 8.0 volume percentage. Analgesic management of continuous remifentanil was utilized with epidural management, which optimized HTN and tolerance to IRE therapy. CONCLUSIONS: Anesthetic management for IRE of soft tissue deviates from standard anesthetic medical therapy in regards to depth of neuromuscular blockade and analgesic management during IRE energy delivery. However, minor modifications in anesthesia management allow for a safe and efficient patient procedure. PMID- 26161320 TI - Addition of Intrathecal Magnesium Sulfate to Bupivacaine for Spinal Anesthesia in Cesarean Section. AB - BACKGROUND: Spinal anesthesia is widely used for caesarean section. Addition of intrathecal magnesium sulfate to local anesthetics seems to improve the quality of block and prolong the duration of analgesia. OBJECTIVES: The present study was designed to examine whether addition of intrathecal magnesium sulfate enhances the analgesic efficacy of intrathecal bupivacaine in patients undergoing cesarean section. PATIENTS AND METHODS: We conducted a randomized, prospective, double blind, case-control, clinical trial. Eighty patients were scheduled for cesarean section under spinal anesthesia. The patients were randomly allocated to receive either 10 mg of hyperbaric bupivacaine 0.5% (control group) or 10 mg of hyperbaric bupivacaine 0.5% plus 50 mg magnesium sulfate (case group) intrathecally. Hemodynamic variability, onset and duration of block and duration of analgesia were evaluated. RESULTS: The onset of sensory blockade was delayed in case group compared with control group, and this was statistically significant. The onset of motor blockade had no difference in both groups. The duration of motor blockade was similar. Post-operative analgesia was longer in magnesium sulfate group but the difference was not meaningful. The intraoperative hemodynamic variability showed no significant differences between groups. CONCLUSIONS: This study showed that the addition of intrathecal magnesium sulfate to bupivacaine is not desirable in patients undergoing cesarean section due to the delay in the onset of sensory blockade and the lack of significant effects of magnesium on post-operative pain. PMID- 26161321 TI - The Analgesic Effects of Morphine and Tramadol Added to Intra-articular Levobupivacaine-Tenoxicam Combination for Arthroscopic Knee Surgery on Postoperative Pain; a Randomized Clinical Trial. AB - BACKGROUND: Arthroscopic knee surgery is commonly performed as an outpatient procedure and is often associated with postoperative pain. OBJECTIVES: We aimed to compare the effects of intra-articular levobupivacaine-tenoxicam-tramadol and levobupivacaine-tenoxicam-morphine combinations on postoperative pain in patients undergoing elective arthroscopic knee surgery. MATERIALS AND METHODS: A total of 90 ASA I-II patients undergoing elective arthroscopic meniscectomy under general anesthesia were enrolled. The participants were randomly allocated to three groups to receive the following intra-articular medications after completion of the surgery and before deflation of the tourniquet: Group S, 20 mL of saline; Group T, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 100 mg of tramadol in 20 mL saline; and Group M, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 4 mg of morphine in 20 mL saline. Visual analogue scale values at rest (VASr) and at active flexion of knee (VASa) at postoperation hours 1, 2, 4, 8, 12, and 24, duration of analgesia, total analgesic consumption, and number of rescue analgesia at 24 hours were evaluated. RESULTS: VASr and VASa were significantly higher in group S in comparison to other groups (P < 0.05). Duration of analgesia was significantly longer in Group T and Group M than in Group S (P < 0.05). The difference between group T and group M was also significant (P < 0.05). Number of rescue analgesia and total analgesic consumption at postoperative hour 24 was significantly fewer in group M compared with other groups (P < 0.05). CONCLUSIONS: Intra-articular levobupivacaine-tenoxicam-morphine combination provides effective pain relief, longer analgesic duration, and less analgesic requirement when compared with intra-articular levobupivacaine-tenoxicam-tramadol combination and saline after knee arthroscopic surgery. PMID- 26161322 TI - Subclavian Vein Cannulation Success Rate in Neonates and Children. AB - BACKGROUND: Central vein cannulation allows the administration of large volumes of fluids in short times and at high osmolarities for rehydration, volume replacement, chemotherapy, and parenteral nutrition. Percutaneous central venous line insertion has replaced peripheral venous cut-down as the primary mode of short-term venous access in children. OBJECTIVES: The aim of our study was to delineate some aspects of this procedure as well as its success rate and relative risk in pediatrics. PATIENTS AND METHODS: Totally, 3264 subclavian vein cannulations in neonates and children were analyzed regarding successful catheterization attempts and early complication rates after the procedure retrospectively in Mofid Hospital (Tehran, Iran). RESULTS: There were 1340 newborn patients (first 28 days of life) in our study population. In these newborns, only 55 cannulations failed; one patient was complicated with pneumothorax; guide wires malfunctioned in 21 cases; and first- attempt cannulation success was reported in only 981 cases. In the remaining 1924 patients, between one month and 8 years old, only 14 attempts at the cannulation of the subclavian vein failed and 1655 cases had first-attempt cannulation success. CONCLUSIONS: The cannulation of the central vein in neonates and children in a skilled hand would be performed with great success rate and low complications. PMID- 26161323 TI - Anesthesia Preoperative Clinic Referral for Elevated Hba1c Reduces Complication Rate in Diabetic Patients Undergoing Total Joint Arthroplasty. AB - BACKGROUND: Diabetes mellitus (DM) is risk factor for complications after orthopedic surgery. OBJECTIVES: We tested the hypothesis that anesthesia preoperative clinic (APC) referral for elevated glycosylated hemoglobin (HbA1c) reduces complication rate after total joint arthroplasty (TJA). PATIENTS AND METHODS: Patients (n = 203) with and without DM were chosen from 1,237 patients undergoing TJA during 2006 - 12. Patients evaluated in the APC had surgery in 2006 - 8 regardless of HbA1c (uncontrolled). Those evaluated between in subsequent two-year intervals were referred to primary care for HbA1c >= 10% and >= 8%, respectively, to improve DM control before surgery. Complications and mortality were quantified postoperatively and at three, six, and twelve months. Length of stay (LOS) and patients requiring a prolonged LOS (> 5 days) were recorded. RESULTS: Patients (197 men, 6 women) underwent 71, 131, and 1 total hip, knee, and shoulder replacements, respectively. Patients undergoing TJA with uncontrolled HbA1c and those with HbA1c < 10%, but not those with HbA1c < 8%, had a higher incidence of coronary disease and hypercholesterolemia than patients without DM. An increase in complication rate was observed in DM patients with uncontrolled HbA1c versus patients without DM (P < 0.001); the complication rate progressively decreased with tighter HbA1c control. More DM patients with preoperative HbA1c that was uncontrolled or >= 10% required prolonged LOS versus those without DM (P < 0.001 and P = 0.0404, respectively). CONCLUSIONS: APC referral for elevated HbA1c reduces complication rate and the incidence of prolonged hospitalization during the first year after surgery in diabetics undergoing TJA. PMID- 26161324 TI - Real-Time Ultrasound Guided the New Standard Technique for Percutaneous Dilatational Tracheostomy (PDT). PMID- 26161325 TI - Oral Dexmedetomidine Versus Midazolam as Anesthetic Premedication in Children Undergoing Congenital Heart Surgery. AB - BACKGROUND: Premedication is required for reducing anxiety and child's struggling against mask acceptance on anesthesia in pediatric surgery for congenital heart disease. Midazolam has been widely used for this purpose, but because of its side effects, finding an effective replacement with less complication is necessary. OBJECTIVES: In the present study, we compared the efficacy of oral midazolam versus dexmedetomidine in terms of anxiolysis and mask acceptance behavior. PATIENTS AND METHODS: Sixty children aged between 2 and 12 years, and scheduled for on-pump surgery due to a congenital heart disease were randomly assigned into two groups. Oral midazolam (0.5 mg/kg up to 15 mg per patient) and dexmedetomidine (2 ug/kg) were administered 45 minutes pre-anesthesia. Children's anxiety, mask acceptance behavior, hemodynamic measures, and cardiopulmonary outcomes were recorded and compared. RESULTS: The mean age of patients was 3.96 +/- 2.04 years. Twenty-eight (46.7%) patients were females. Two drugs have similar effects on cardiopulmonary outcomes and hemodynamic measures (P > 0.05). They equally relieved the children's anxiety (mean sedation score 1.93 +/- 0.63 and 2.0 +/- 0.63 for midazolam and dexmedetomidine groups, respectively; P > 0.05), while dexmedetomidine showed a better effect on improving the mask acceptance behavior (mean mask acceptance score 2.58 +/- 0.6 and 1.6 +/- 0.67 for midazolam and dexmedetomidine, respectively; P < 0.05). CONCLUSIONS: It appears reasonable to apply oral premedication with dexmedetomidine 45 minutes before transferring the patient to the operating room when he or she is more prone to resist inhalation anesthesia induction. PMID- 26161326 TI - The Effects of Topical Sesame (Sesamum indicum) Oil on Pain Severity and Amount of Received Non-Steroid Anti-Inflammatory Drugs in Patients With Upper or Lower Extremities Trauma. AB - BACKGROUND: Most patients with trauma experience different levels of pain. Due to side effects as well as economic burden of drugs used for pain relief after trauma commonly, it is important to use low-cost methods independently or combined with drugs to alleviate pain. OBJECTIVES: Therefore, this study aimed to investigate the effects of topical sesame oil on pain severity and frequency of received NSAIDs of patients with trauma. PATIENTS AND METHODS: This randomized clinical trial study was conducted on 150 patients with upper or lower extremities trauma in Dezful Ganjavian Hospital, Ahvaz, Iran, in 2014. Data was collected by a researcher-made questionnaire and Visual Analogue Scale (VAS). Patients were divided into two groups of control (n = 75) and intervention (n = 75) randomly. In the intervention group, patients applied topical sesame oil beside the routine cares, while in the control group patients just received routine cares. Severity of pain and frequency of received NSAIDs was assessed in the first, third, seventh and tenth days after the intervention in the both groups. Data was analyzed by SPSS19 software using descriptive and analytic (Chi square and independent sample t-test) statistical methods. RESULTS: Based on student sample t-test, there was a significant difference between intervention and control groups regarding the pain severity in the first (P = 0.06), third (P = 0.001), seventh (P = 0.001) and tenth (P = 0.001) days after the intervention. Besides, the frequency of received NSAIDs in the intervention group and the control group showed significant difference in four days after the intervention (for four days P = 0.001). CONCLUSIONS: Topical application of sesame oil could reduce pain severity and frequency of received NSAIDs in patients with upper or lower extremities trauma. Therefore, it is recommended to use this oil in complementary medicine for pain relief due to low cost, easy usage and lack of adverse effects. PMID- 26161327 TI - The Effects of Nitroglycerine on Pain Control During the Propofol Injection; a Controlled, Double-Blinded, Randomized Clinical Trial. AB - BACKGROUND: The use of Propofol often results in pain upon injection, which is sometimes very distressing for patients. Many patients report some degree of pain or discomfort on injection with propofol. Injection-induced pain during induction of anesthesia can result in patient's discomfort. OBJECTIVES: This study was performed to evaluate the effects of nitroglycerine on pain severity in patients undergoing propofol injection. PATIENTS AND METHODS: In this double-blind randomized clinical trial, 100 patients with ASA class I and II undergoing anesthesia with propofol injection were selected for the study from 2012 to 2013 in Imam Reza training hospital. Patients were randomly assigned to case and control groups and received either 20 MUg of nitroglycerine or normal saline as placebo. The severity of injection pain was assessed using a four-point scale. An anesthesiologist observed hemodynamic and local adverse effects. RESULTS: The pain severity in nitroglycerine group was significantly lower compared with the placebo group (P < 0.0001). Moreover, the local adverse reactions were observed only in three patients in the placebo group while no patient in the drug group experienced adverse effects (P = 0.242). The systolic blood pressure showed no significant difference between two groups before and after the induction of anesthesia but the diastolic blood pressure and the heart rate was significantly different between study groups. CONCLUSIONS: Nitroglycerine may be a safe and effective adjuvant therapeutic for pain reduction in patients under propofol injection. Hence, its use for reduction of propofol injection-induced pain is recommended. PMID- 26161328 TI - Intraperitoneal Bupivacaine-Meperidine Infiltration Versus Intravenous Paracetamol: A Comparison of Analgesic Efficacy in Post-Gynecologic Diagnostic Laparoscopic Pain. AB - BACKGROUND: Pain following laparoscopy could be due to different causes requiring effective postoperative analgesia. OBJECTIVES: In the present study, we evaluated the combined effect of intraperitoneal infiltration of bupivacaine-meperidine versus intravenous infusion of paracetamol on pain relief after diagnostic gynecologic laparoscopy. PATIENTS AND METHODS: In this prospective study, 90 female subjects with ASA class I or II scheduled for gynecologic diagnostic laparoscopy were studied in two groups; group B + M received intraperitoneal infiltration of 40 mL bupivacaine 0.25% with 50 mg of meperidine, group P received normal saline via abdominal trocar and ten minutes before the end of operation, group P received infusion of paracetamol 1000 mg in normal saline. Postoperative pain was evaluated using VAS score in PACU and 1, 2, 4, 8, 12 and 24 hours after the operation. The time to the first analgesic administration and total analgesic requirements were recorded. RESULTS: Group B + M had significantly lower pain score in the first 8 postoperative hours than group P (P < 0.05). Rescue meperidine (IM) requirement was significantly less in B + M group compared to group P. Time to first request for analgesia was different between the two groups (78 versus 60 min); however, the difference was not statistically significant. CONCLUSIONS: Intraperitoneal Infiltration of bupivacaine with meperidine following surgery provided more appropriate analgesia after gynecologic diagnostic laparoscopy than administration of IV paracetamol. PMID- 26161329 TI - Seizure in Pregnancy Following Cerebral Venous Sinus Thrombosis. AB - INTRODUCTION: Seizure involves less than 1% of pregnancies; however it is associated with increased maternal and fetal complications. Cerebral venous sinus thrombosis is a rare, but potentially life-threatening cause of seizure during pregnancy, presenting primarily as seizure in 12% - 31.9% of cases. Pregnancy and puerperium are known as the risk factors of cerebral venous sinus thrombosis. CASE PRESENTATION: Here is presented a case of seizure after delivery by cesarean section in an otherwise healthy woman. The final diagnosis was cerebral venous sinus thrombosis probably due to hypercoagulable state in pregnancy. CONCLUSIONS: If seizure occurs during the peripartum period, along with providing complete cardiovascular and respiratory support, advanced diagnostic measures are needed and cerebral venous sinus thrombosis should be considered as a possible diagnosis. PMID- 26161330 TI - Hemodynamic Responses to Two Different Anesthesia Regimens in Compromised Left Ventricular Function Patients Undergoing Coronary Artery Bypass Graft Surgery: Etomidate-Midazolam Versus Propofol-Ketamine. AB - BACKGROUND: Various methods have been suggested to prevent hemodynamic instability caused by propofol and adverse effects caused by etomidate induction. The current study evaluated hemodynamic effects of propofol-ketamine mixture in comparison to etomidate-midazolam mixture during anesthesia induction. OBJECTIVES: The aim of this study was to evaluate the hemodynamic effects of etomidate-midazolam by comparing it with propofol-ketamine for the induction of anesthesia in patients with left ventricular dysfunction undergoing coronary artery bypass graft surgery. PATIENTS AND METHODS: One-hundred patients aged between 40 and 65 with coronary artery disease and low ejection fraction scheduled for elective coronary artery bypass surgery participated in this study. The patients were randomly allotted to one of the two groups to receive either propofol-ketamine or etomidate-midazolam combination. Two groups were compared for pain on injection and myoclonus, Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP), Cardiac Index (CI) and Systemic Vascular Resistance (SVR), before and one minute after induction of anesthesia, and one, three and five minutes after intubation. RESULTS: Incidence of pain on injection (2 - 4%) and myoclonus (10%) was less in both groups. The hemodynamic response was similar in the two groups for all variables over the time interval, except for CI at one and three minutes after intubation (P = 0.024 and P = 0.048, respectively), and SVR in five minutes after intubation (P = 0.009), with differences being statistically significant. CONCLUSIONS: Both anesthetic regimens were acceptable for induction in patients with coronary artery disease and left ventricular dysfunction undergoing coronary artery bypass graft surgery. PMID- 26161332 TI - Artificial oocyte activation in intracytoplasmic sperm injection cycles using testicular sperm in human in vitro fertilization. AB - OBJECTIVE: Artificial oocyte activation (AOA) is an effective method to avoid total fertilization failure in human in vitro fertilization-embryo transfer (IVF ET) cycles. AOA performed using a calcium ionophore can induce calcium oscillation in oocytes and initiate the fertilization process. We evaluated the usefulness of AOA with a calcium ionophore in cases of total fertilization failure in previous cycles and in cases of severe male factor infertility patients with non-motile spermatozoa after pentoxifylline (PF) treatment. METHODS: The present study describes 29 intracytoplasmic sperm injection (ICSI) AOA cycles involving male factor infertility at Cheil General Hospital from January 2006 to June 2013. Patients were divided into two groups (control, n=480; AOA, n=29) depending on whether or not AOA using a calcium ionophore (A23187) was performed after testicular sperm extraction-ICSI (TESE-ICSI). The AOA group was further split into subgroups according to sperm motility after PF treatment: i.e., motile sperm-injected (n=12) and non-motile sperm-injected (n=17) groups (total n=29 cycles). RESULTS: The good embryo rate (52.3% vs. 66.9%), pregnancy rate (20.7% vs. 52.1%), and delivery rate (10.3% vs. 40.8%) were lower in the PF/AOA group than in the control group. When evaluating the effects of restoration of sperm motility after PF treatment on clinical outcomes there was no difference in fertilization rate (66.6% vs. 64.7% in non-motile and motile sperm, respectively), pregnancy rate (17.6% vs. 33.3%), or delivery rate (5.9% vs. 16.7%) between the two groups. CONCLUSION: We suggest that oocyte activation is a useful method to ensure fertilization in TESE-ICSI cycles regardless of restoration of sperm motility after PF treatment. AOA may be useful in selected patients who have a low fertilization rate or total fertilization failure. PMID- 26161331 TI - Artificial gametes from stem cells. AB - The generation of artificial gametes is a real challenge for the scientific community today. In vitro development of human eggs and sperm will pave the way for the understanding of the complex process of human gametogenesis and will provide with human gametes for the study of infertility and the onset of some inherited disorders. However, the great promise of artificial gametes resides in their future application on reproductive treatments for all these people wishing to have genetically related children and for which gamete donation is now their unique option of parenthood. This is the case of infertile patients devoid of suitable gametes, same sex couples, singles and those fertile couples in a high risk of transmitting serious diseases to their progeny. In the search of the best method to obtain artificial gametes, many researchers have successfully obtained human germ cell-like cells from stem cells at different stages of differentiation. In the near future, this field will evolve to new methods providing not only viable but also functional and safe artificial germ cells. These artificial sperm and eggs should be able to recapitulate all the genetic and epigenetic processes needed for the correct gametogenesis, fertilization and embryogenesis leading to the birth of a healthy and fertile newborn. PMID- 26161333 TI - Effect of laser-assisted multi-point zona thinning on development and hatching of cleavage embryos in mice. AB - OBJECTIVE: This study aimed to examine the effect of laser-assisted zona thinning (LAZT) at one or four-points on the blastocyst formation and hatching process in mice with respect to female age. METHODS: Eight-cell or morula embryos collected from superovulated C57BL female mice with different ages (6-11 and 28-31 weeks) were treated with LAZT at one-point (LAZT1) or four-points (LAZT4). The zona pellucida was thinned to more than 70% of its initial thickness by making two holes of 15-20 um. RESULTS: In the young mice, LAZT resulted in a significant increase in early hatching and hatching rates compared to the control group (p<0.05). However, in the old mice, LAZT significantly increased blastocyst formation as well as early hatching and hatching compared to the controls (p<0.05). These effects were more remarkable in LAZT4 than in LAZT1 and in aged mice than in young ones. CONCLUSION: These results show that multi-point LAZT leads to a significant improvement of blastocyst formation and hatching in mice compared to controls. PMID- 26161334 TI - Analysis of C43G mutation in the promoter region of the XIST gene in patients with idiopathic primary ovarian insufficiency. AB - OBJECTIVE: The XIST gene is considered to be an attractive candidate gene for skewed X-chromosome inactivation and a possible cause of primary ovarian insufficiency (POI). The purpose of this study was to investigate whether the XIST gene promoter mutation is associated with idiopathic POI in a sample of the Korean population. METHODS: Subjects consisted of 102 idiopathic POI patients and 113 healthy controls with normal menstrual cycles. Patients with the following known causes of POI were excluded in advance: cytogenetic abnormalities, prior chemo- or radiotherapy, or prior bilateral oophorectomy. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The mean age of onset of ovarian insufficiency was 28.7+/-8.5 years and the mean values of serum luteinizing and follicle-stimulating hormones and estradiol in the POI group were 31.4+/-18.2 mIU/mL, 74.5+/-41.1 mIU/mL, and 30.5+/-36.7 pg/mL, respectively. We found no cytosine to guanine (C43G) variation in the XIST gene in both POI patients and controls. CONCLUSION: The C43G mutation in the promoter region of the XIST gene was not present in the Korean patients with idiopathic POI in our study, in contrast to our expectation, suggesting that the role of XIST in the pathogenesis of POI is not yet clear. PMID- 26161335 TI - Efficacy of corifollitropin alfa followed by recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist protocol for Korean women undergoing assisted reproduction. AB - OBJECTIVE: To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. METHODS: Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. RESULTS: There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. CONCLUSION: Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS. PMID- 26161336 TI - Factors influencing serum progesterone level on triggering day in stimulated in vitro fertilization cycles. AB - OBJECTIVE: Elevated serum progesterone (P) levels on triggering day have been known to affect the pregnancy rate of in vitro fertilization (IVF). This study aimed to identify the possible factors influencing serum P levels on triggering day in stimulated IVF cycles. METHODS: Three hundred and thirty consecutive fresh IVF cycles were included in the study. All cycles were first attempts and were performed in a single infertility center. The indications for IVF were male factor infertility (n=114), ovulatory infertility (n=84), endometriosis (n=61), tubal infertility (n=59), unexplained infertility (n=41), and uterine factor infertility (n=39). A luteal long protocol of a gonadotropin-releasing hormone (GnRH) agonist (n=184) or a GnRH antagonist protocol (n=146) was used for pituitary suppression. Ovarian sensitivity was defined as the serum estradiol level on triggering day per 500 IU of administered gonadotropins (OS[a]) or the retrieved oocyte number per 500 IU of administered gonadotropins (OS[b]). RESULTS: Univariate analysis revealed that the serum P level on triggering day was associated with the serum estradiol level on triggering day (r=0.379, p<0.001), the number of follicles >=14 mm (r=0.247, p<0.001), the number of retrieved oocytes (r=0.384, p<0.001), and ovarian sensitivity (OS[a]: r=0.245, p<0.001; OS[b]: r=0.170, p=0.002). The woman's age, body mass index, antral follicle count, and basal serum follicle stimulating hormone and estradiol levels were not associated with serum P level on triggering day. The serum P level on triggering day did not show significant variation depending on the type or cause of infertility, pituitary suppression protocol, or the type of gonadotropins used. CONCLUSION: The serum P level on triggering day was closely related to the response to ovarian stimulation. PMID- 26161337 TI - A case of 17 alpha-hydroxylase deficiency. AB - 17alpha-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In 17alpha hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with 17alpha-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with 17alpha-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with 17alpha-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder. PMID- 26161338 TI - Effect of Exercise on u-Opioid Receptor Expression in the Rostral Ventromedial Medulla in Neuropathic Pain Rat Model. AB - OBJECTIVE: To investigate the effects of aerobic exercise on neuropathic pain and verify whether regular treadmill exercise alters opioid receptor expression in the rostral ventral medulla (RVM) in a neuropathic pain rat model. METHODS: Thirty-two male Sprague-Dawley rats were used in the study. All rats were divided into 3 groups, i.e., group A, sham group (n=10); group B, chronic constriction injury (CCI) group (n=11); and group C, CCI+exercise group (n=11). Regular treadmill exercise was performed for 30 minutes a day, 5 days a week, for 4 weeks at the speed of 8 m/min for 5 minutes, 11 m/min for 5 minutes, and 22 m/min for 20 minutes. Withdrawal threshold and withdrawal latency were measured before and after the regular exercise program. Immunohistochemistry and Western blots analyses were performed using antibodies against u-opioid receptor (MOR). RESULTS: Body weight of group C was the lowest among all groups. Withdrawal thresholds and withdrawal latencies were increased with time in groups B and C. There were significant differences of withdrawal thresholds between group B and group C at 1st, 2nd, 3rd, and 4th weeks after exercise. There were significant differences of withdrawal latencies between group B and group C at 3rd and 4th weeks after exercise. MOR expression of group C was significantly decreased, as compared to that of group B in the RVM and spinal cord. CONCLUSION: In neuropathic pain, exercise induced analgesia could be mediated by desensitization of central MOR by endogenous opioids, leading to the shift of RVM circuitry balance to pain inhibition. PMID- 26161339 TI - Analysis of the Correlation Among Age, Disc Morphology, Positive Discography and Prognosis in Patients With Chronic Low Back Pain. AB - OBJECTIVE: To investigate the correlation among age, disc morphology, positive discography, and prognosis in patients with chronic low back pain. METHODS: A total of 183 intervertebral discs in 72 patients with chronic low back pain were studied. Discography was performed using a pressure-controlled manometric technique. The pain reaction during discography at each level was recorded as follows: no pain, dissimilar pain, similar pain, or concordant pain. Discs with similar or concordant pain were classified as positive. All the examined discs were assessed morphologically using axial computed tomography imaging. The grade of general degeneration and annular disruption of the discs were assessed according to the Dallas discogram description (DDD). Intradiscal injection of steroid was tried for patients with symptomatic disc identified during provocative discography and who did not consent to surgical operation. RESULTS: There was a higher correlation between general degeneration and age, as compared with annular disruption and age. Higher general degeneration and annular disruption grades had higher positive rates of discography. However, annular disruption alone was independently associated with positive discography. Age and grade of general degeneration did not affect the prognosis. CONCLUSION: The grade of general degeneration was associated with age, but it was not correlated with positive discography and prognosis. In addition, high grade of annular disruption correlated with positive discography. PMID- 26161340 TI - Limb Differences in the Therapeutic Effects of Complex Decongestive Therapy on Edema, Quality of Life, and Satisfaction in Lymphedema Patients. AB - OBJECTIVE: To investigate the changing patterns of edema, quality of life (QOL), and patient-satisfaction after complex decongestive therapy (CDT) in three trajectories: arm lymphedema (AL), secondary leg lymphedema (LL) and primary leg lymphedema (PL). METHODS: Candidates for AL (n=35), LL (n=35) and PL (n=14) were identified from prospective databases. The patients were treated with CDT for 2 weeks, and lymphedema volume was measured before and immediately following the therapy. Patients then self-administered home therapy for 3 months and presented for a follow-up visit. The Korean version of Short Form-36 (SF-36) was used to assess QOL, and we administered a study-specific satisfaction survey. RESULTS: There was no significant difference in the volume reductions between the 3 groups. There were no significant differences in all of the measures between PL and LL. Overall initial QOL was significantly lower in patients with LL than in patients with AL. SF-36 scores post-CDT did not differ significantly between AL and LL. Clinically significant differences were noted between AL and LL in the mean values of the satisfaction survey. CONCLUSION: AL, LL, and PL may have different longitudinal courses. We suggest that lower extremity lymphedema patients present more favorable outcomes after CDT with respect to QOL and satisfaction than upper extremity lymphedema patients. Clinicians should approach patients with different therapeutic considerations specific to each type or region of lymphedema before using CDT in clinical practice. PMID- 26161341 TI - Effects of Incentive Spirometry on Respiratory Motion in Healthy Subjects Using Cine Breathing Magnetic Resonance Imaging. AB - OBJECTIVE: To investigate the effectiveness of incentive spirometry on respiratory motion in healthy subjects using cine breathing magnetic resonance imaging (MRI). METHODS: Ten non-smoking healthy subjects without any history of respiratory disease were studied. Subjects were asked to perform pulmonary training using incentive spirometry every day for two weeks. To assess the effectiveness of this training, pulmonary function tests and cine breathing MRI were performed before starting pulmonary training and two weeks after its completion. RESULTS: After training, there were significant improvements in vital capacity (VC) from 3.58+/-0.8 L to 3.74+/-0.8 L and in %VC from 107.4+/-10.8 to 112.1+/-8.2. Significant changes were observed in the right diaphragm motion, right chest wall motion, and left chest wall motion, which were increased from 55.7+/-9.6 mm to 63.4+/-10.2 mm, from 15.6+/-6.1 mm to 23.4+/-10.4 mm, and from 16.3+/-7.6 mm to 22.0+/-9.8 mm, respectively. CONCLUSION: Two weeks of training using incentive spirometry provided improvements in pulmonary function and respiratory motion, which suggested that incentive spirometry may be a useful preoperative modality for improving pulmonary function during the perioperative period. PMID- 26161342 TI - Efficacy of Systemic Postoperative Pulmonary Rehabilitation After Lung Resection Surgery. AB - OBJECTIVE: To investigate the efficacy of systemic pulmonary rehabilitation (PR) after lung resection in patients with lung cancer. METHODS: Forty-one patients undergoing lung resection were enrolled and classified into the experimental (n=31) and control groups (n=10). The experimental group underwent post-operative systemic PR which was conducted 30 min/day on every hospitalization day by an expert physical therapist. The control group received the same education about the PR exercises and were encouraged to self-exercise without supervision of the physical therapist. The PR group was taught a self-PR program and feedback was provided regularly until 6 months after surgery. We conducted pulmonary function testing (PFT) and used a visual analog scale (VAS) to evaluate pain, and the modified Borg Dyspnea Scale (mBS) to measure perceived respiratory exertion shortly before and 2 weeks, 1, 3, and 6 months after surgery. RESULTS: A significant improvement on the VAS was observed in patients who received systemic PR >3 months. Significant improvements in forced vital capacity (FVC) and mBS score were observed in patients who received systemic PR >6 months (p<0.05). Other PFT results were not different compared with those in the control group. CONCLUSION: Patients who received lung resection suffered a significant decline in functional reserve and increases in pain and subjective dyspnea deteriorating quality of life (QoL). Systemic PR supervised by a therapist helped improve reduced pulmonary FVC and QoL and minimized discomfort during the postoperative periods in patients who underwent lung resection. PMID- 26161343 TI - Change of Brain Functional Connectivity in Patients With Spinal Cord Injury: Graph Theory Based Approach. AB - OBJECTIVE: To investigate the global functional reorganization of the brain following spinal cord injury with graph theory based approach by creating whole brain functional connectivity networks from resting state-functional magnetic resonance imaging (rs-fMRI), characterizing the reorganization of these networks using graph theoretical metrics and to compare these metrics between patients with spinal cord injury (SCI) and age-matched controls. METHODS: Twenty patients with incomplete cervical SCI (14 males, 6 females; age, 55+/-14.1 years) and 20 healthy subjects (10 males, 10 females; age, 52.9+/-13.6 years) participated in this study. To analyze the characteristics of the whole brain network constructed with functional connectivity using rs-fMRI, graph theoretical measures were calculated including clustering coefficient, characteristic path length, global efficiency and small-worldness. RESULTS: Clustering coefficient, global efficiency and small-worldness did not show any difference between controls and SCIs in all density ranges. The normalized characteristic path length to random network was higher in SCI patients than in controls and reached statistical significance at 12%-13% of density (p<0.05, uncorrected). CONCLUSION: The graph theoretical approach in brain functional connectivity might be helpful to reveal the information processing after SCI. These findings imply that patients with SCI can build on preserved competent brain control. Further analyses, such as topological rearrangement and hub region identification, will be needed for better understanding of neuroplasticity in patients with SCI. PMID- 26161344 TI - Comparison of Fat Mass Percentage and Body Mass Index in Koreans With Spinal Cord Injury According to the Severity and Duration of Motor Paralysis. AB - OBJECTIVE: To analyze the relationship of the change in fat mass percentage (FMP) and body mass index (BMI) with the change in obesity rate according to gender, extent of spinal cord injury (SCI) and the duration. METHODS: The retrospective study was conducted with medical records of 915 patients. FMP was calculated with BMI and bioelectrical impedance analysis (BIA). Statistical analysis of the relationship between FMP and gender, extent of SCI and the duration after SCI was done. RESULTS: FMP increased in relation to the duration. The mean FMP was higher in the motor complete tetraplegia group, as compared to the motor incomplete group. The rate of obesity was 69.8% with cutoff FMP values of over 22% and 35% for male and female patients, respectively. Rate of obesity was correlated with the duration after SCI and degree of paralysis. The rate of obesity was 17.1% with a cutoff value of BMI 25 kg/m(2) and 51.3% with a cutoff value of 22 kg/m(2). For evaluation of the diagnostic value of BMI to predict obesity according to FMP standards, a cutoff value of 25 kg/m(2) showed a sensitivity level of 22.3% and specificity level of 94.9%. When the cutoff level for BMI was set at 22 kg/m(2), the sensitivity and specificity were 59.3% and 67.0%, respectively. CONCLUSION: In Korean SCI patients, FMP showed good correlation with the duration of SCI and the extent of SCI, while BMI did not. Especially in the motor complete tetraplegia group, the diagnostic value of BMI decreased as the duration after SCI increased. This study suggested that FMP could be used complementarily when evaluating the obesity of SCI patients. PMID- 26161345 TI - Evaluation of Stiffness of the Spastic Lower Extremity Muscles in Early Spinal Cord Injury by Acoustic Radiation Force Impulse Imaging. AB - OBJECTIVE: To investigate intrinsic viscoelastic changes using shear wave velocities (SWVs) of spastic lower extremity muscles in patients with early spinal cord injury (SCI) via acoustic radiation force impulse (ARFI) imaging and to evaluate correlation between the SWV values and spasticity. METHODS: Eighteen patients with SCI within 3 months and 10 healthy adults participated. We applied the ARFI technique to measure SWV of gastrocnemius muscle (GCM) and long head of biceps femoris muscle. Spasticity of ankle and knee joint was assessed by original Ashworth Scale. RESULTS: Ten patients with SCI had spasticity. Patients with spasticity had significantly faster SWV for GCM and biceps femoris muscle than those without spasticity (Mann-Whitney U test, p=0.007 and p=0.008) and normal control (p=0.011 and p=0.037, respectively). The SWV values of GCM correlated with the ankle spasticity (Spearman rank teat, p=0.026). There was significant correlation between the SWV values for long head of biceps femoris muscle and knee spasticity (Spearman rank teat, p=0.022). CONCLUSION: ARFI demonstrated a difference in muscle stiffness in the GCM between patients with spastic SCI and those without spasticity. This finding suggested that stiffness of muscles increased in spastic lower extremity of early SCI patients. ARFI imaging is a valuable tool for noninvasive assessment of the stiffness of the spastic muscle and has the potential to identify pathomechanical changes of the tissue associated with SCI. PMID- 26161346 TI - Effect of Motor Imagery on the F-Wave Parameters in Hemiparetic Stroke Survivors. AB - OBJECTIVE: To assess the effect of motor imagery, as a rehabilitation method in stroke, on F-wave parameters that undergo changes during upper motor neuron involvement. METHODS: Twenty-one fully conscious hemiparetic stroke survivors with a completely plegic hand (power 0/5) and a minimum interval of 72 hours since stroke were recruited into this study. The mean F-wave latency, amplitude, and persistence in the median and ulnar nerves were measured in both the affected and non-affected sides at rest and in the paretic hand during a mental task. Comparison was made between data from the affected hand and the non-affected hand as well as between data from the affected hand at baseline and during motor imagery. RESULTS: Patients had significantly different F-wave persistence between the affected and non-affected sides (paired t-test, p<0.001). Motor imagery could improve F-wave persistence in both the investigated nerves (paired t-test, p=0.01 for ulnar nerve and p<0.001 for median nerve) and F-response amplitude in the median nerve (paired t-test, p=0.01) of the affected limb. CONCLUSION: The amplitude and persistence of F-wave were improved during motor imagery, representing F-wave facilitation. This result suggests that motor imagery can restore motor neuron excitability, which is depressed after stroke. PMID- 26161347 TI - Analysis of Vertical Ground Reaction Force Variables Using Foot Scans in Hemiplegic Patients. AB - OBJECTIVE: To analyze the differences in the vertical ground reaction force (GRF) variables of hemiplegic patients compared with a control group, and between the affected and unaffected limbs of hemiplegic patients using foot scans. METHODS: Patients (n=20) with hemiplegia and healthy volunteers (n=20) underwent vertical force analysis. We measured the following: the first and second peak forces (F1, F2) and the percent stances at which they occurred (T1, T2); the vertical force impulse (VFI) and stance times. The GRF results were compared between the hemiplegic patients and control individuals, and between the affected and unaffected limbs of hemiplegic patients. Additionally, we analyzed the impulse of the unaffected limb according to the motor assessment scale (MAS), Brunnstrom stage, and a Timed Up and Go Test. RESULTS: The F1s and F2s of the affected and unaffected limbs were significantly less than those of the normal control individuals (p<0.05). The T1s of both the affected and unaffected limbs of the patients were greater than control individuals, whilst the T2s were lower (p<0.05). Greater impulses and stance times were recorded on both sides of the patients than in the limbs of the control individuals (p<0.05). The MAS, Brunnstrom stage and Timed Up and Go Test results were significantly correlated with the VFI of the unaffected limbs (p<0.05). CONCLUSION: The high impulse values of the unaffected limb were associated with complications during gait rehabilitation. Therefore, these results suggest that unaffected limbs should also be taken into consideration in these patients. PMID- 26161348 TI - Effect of Epidural Electrical Stimulation and Repetitive Transcranial Magnetic Stimulation in Rats With Diffuse Traumatic Brain Injury. AB - OBJECTIVE: To evaluate the effects of epidural electrical stimulation (EES) and repetitive transcranial magnetic stimulation (rTMS) on motor recovery and brain activity in a rat model of diffuse traumatic brain injury (TBI) compared to the control group. METHODS: Thirty rats weighing 270-285 g with diffuse TBI with 45 kg/cm(2) using a weight-drop model were assigned to one of three groups: the EES group (ES) (anodal electrical stimulation at 50 Hz), the rTMS group (MS) (magnetic stimulation at 10 Hz, 3-second stimulation with 6-second intervals, 4,000 total stimulations per day), and the sham-treated control group (sham) (no stimulation). They were pre-trained to perform a single-pellet reaching task (SPRT) and a rotarod test (RRT) for 14 days. Diffuse TBI was then induced and an electrode was implanted over the dominant motor cortex. The changes in SPRT success rate, RRT performance time rate and the expression of c-Fos after two weeks of EES or rTMS were tracked. RESULTS: SPRT improved significantly from day 8 to day 12 in the ES group and from day 4 to day 14 in the MS group (p<0.05) compared to the sham group. RRT improved significantly from day 6 to day 11 in ES and from day 4 to day 9 in MS compared to the sham group. The ES and MS groups showed increased expression of c-Fos in the cerebral cortex compared to the sham group. CONCLUSION: ES or MS in a rat model of diffuse TBI can be used to enhance motor recovery and brain activity. PMID- 26161349 TI - Effects of Head Rotation and Head Tilt on Pharyngeal Pressure Events Using High Resolution Manometry. AB - OBJECTIVE: To observe changes in pharyngeal pressure during the swallowing process according to postures in normal individuals using high-resolution manometry (HRM). METHODS: Ten healthy volunteers drank 5 mL of water twice while sitting in a neutral posture. Thereafter, they drank the same amount of water twice in the head rotation and head tilting postures. The pressure and time during the deglutition process for each posture were measured with HRM. The data obtained for these two postures were compared with those obtained from the neutral posture. RESULTS: The maximum pressure, area, rise time, and duration in velopharynx (VP) and tongue base (TB) were not affected by changes in posture. In comparison, the maximum pressure and the pre-upper esophageal sphincter (UES) maximum pressure of the lower pharynx in the counter-catheter head rotation posture were lower than those in the neutral posture. The lower pharynx pressure in the catheter head tilting posture was higher than that in the counter-catheter head tilting. The changes in the VP peak and epiglottis, VP and TB peaks, and the VP onset and post-UES time intervals were significant in head tilting and head rotation toward the catheter postures, as compared with neutral posture. CONCLUSION: The pharyngeal pressure and time parameter analysis using HRM determined the availability of head rotation as a compensatory technique for safe swallowing. Tilting the head smoothes the progress of food by increasing the pressure in the pharynx. PMID- 26161350 TI - Effect of Repetitive Transcranial Magnetic Stimulation According to the Stimulation Site in Stroke Patients With Dysphagia. AB - OBJECTIVE: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) according to the stimulation site in subacute stroke patients with dysphagia. METHODS: This study was designed as a matched comparative study. Twenty-four patients who had dysphagia after ischemic stroke were recruited, and they were divided into two groups after matching for age and stroke lesion. The patients in group A received rTMS over the brain cortex where motor evoked potential (MEP) was obtained from the suprahyoid muscle. Group B received rTMS over the brain cortex where MEP was obtained from the abductor pollicis brevis muscle. rTMS was performed at 110% of MEP threshold, 10 Hz frequency for 10 seconds, and then repeated every minute for 10 minutes. Dysphagia status was measured by the Functional Dysphagia Scale (FDS), the Penetration-Aspiration Scale (PAS), and the Dysphagia Outcome and Severity Scale (DOSS) using the results of a videofluoroscopic swallowing study. These evaluations were measured before, immediately, and 4 weeks after rTMS. RESULTS: Group A showed significant improvement compared to group B in the DOSS score immediately and 4 weeks after rTMS. There were no significant differences in the changes of FDS and PAS scores between groups A and B immediately and 4 weeks after rTMS. CONCLUSION: rTMS over a hot spot for the suprahyoid muscle caused more improvement in swallowing function when compared to that over the interconnected site. PMID- 26161351 TI - Craniofacial Asymmetry in Adults With Neglected Congenital Muscular Torticollis. AB - OBJECTIVE: To evaluate the craniofacial asymmetry in adults with neglected congenital muscular torticollis (CMT) by quantitative assessment based on craniofacial three-dimensional computed tomography (3D-CT). METHODS: Preoperative craniofacial asymmetry was measured by 3D-CT for 31 CMT subjects >=18 years of age who visited a tertiary medical center and underwent 3D-CT between January 2009 and December 2013. The relationship between the age and the severity of craniofacial asymmetry was analyzed in reference to anteroposterior length asymmetry of the frontal bone and zygomatic arch, vertical and lateral displacements of the facial landmarks, and mandibular axis rotation. RESULTS: The age at CT was 27.71+/-7.02 years (range, 18-44 years). All intra-class correlation coefficients were higher than 0.7, suggesting good inter-rater reliability (p<0.05) of all the measurements. The frontal and the zygomatic length ratio (i.e., the anteroposterior length asymmetry on the axial plane) was 1.06+/-0.03 and 1.07+/-0.03, respectively, which was increased significantly with age in the linear regression analysis (r(2)=0.176, p=0.019 and r(2)=0.188, p=0.015, respectively). The vertical or lateral displacement of the facial landmarks and rotation of the mandibular axis did not significantly correlate with age (p>0.05). CONCLUSION: Craniofacial asymmetry of neglected CMT became more severe with age in terms of anteroposterior length asymmetry of the ipsilateral frontal bone and zygomatic arch on the axial plane even after growth cessation. This finding may enhance the understanding of therapeutic strategies for craniofacial asymmetry in adults with neglected CMT. PMID- 26161352 TI - Association Between Evoked Potentials and Balance Recovery in Subacute Hemiparetic Stroke Patients. AB - OBJECTIVE: To investigate the association between baseline motor evoked potential (MEP) and somatosensory evoked potential (SSEP) responses in the lower extremities and balance recovery in subacute hemiparetic stroke patients. METHODS: MEPs and SSEPs were evaluated in 20 subacute hemiparetic stroke patients before rehabilitation. Balance (static posturography and Berg Balance Scale [BBS]), motor function (Fugl-Meyer Assessment [FMA]) and the ability to perform activities of daily living (Modified Barthel Index [MBI]) were evaluated before rehabilitation and after four-weeks of rehabilitation. Posturography outcomes were weight distribution indices (WDI) expressed as surface area (WDI-Sa) and pressure (WDI-Pr), and stability indices expressed as surface area (SI-Sa) and length (SI-L). In addition, all parameters were evaluated during eyes open (EO) and eyes closed (EC) conditions. RESULTS: The MEP (+) group showed significant improvements in balance except WDI-Sa (EC), FMA, and MBI, while the MEP (-) group showed significant improvements in the BBS, FMA, and MBI after rehabilitation. The SSEP (+) group showed significant improvements in balance except SI-Sa (EO), FMA, and MBI, while the SSEPs (-) group showed significant improvements in the BBS, MBI after rehabilitation. The changes in the SI-Sa (EO), SI-L (EO), total MBI, and several detailed MBI subscales in the MEP (+) group after rehabilitation were significantly larger than those in the MEP (-) group. CONCLUSION: Our findings suggest that initial assessments of MEPs and SSEPs might be beneficial when predicting balance recovery in subacute hemiparetic stroke patients. PMID- 26161353 TI - Utility of a Three-Dimensional Interactive Augmented Reality Program for Balance and Mobility Rehabilitation in the Elderly: A Feasibility Study. AB - OBJECTIVE: To improve lower extremity function and balance in elderly persons, we developed a novel, three-dimensional interactive augmented reality system (3D ARS). In this feasibility study, we assessed clinical and kinematic improvements, user participation, and the side effects of our system. METHODS: Eighteen participants (age, 56-76 years) capable of walking independently and standing on one leg were recruited. The participants received 3D ARS training during 10 sessions (30-minute duration each) for 4 weeks. Berg Balance Scale (BBS) and the Timed Up and Go (TUG) scores were obtained before and after the exercises. Outcome performance variables, including response time and success rate, and kinematic variables, such as hip and knee joint angle, were evaluated after each session. RESULTS: Participants exhibited significant clinical improvements in lower extremity balance and mobility following the intervention, as shown by improved BBS and TUG scores (p<0.001). Consistent kinematic improvements in the maximum joint angles of the hip and knee were observed across sessions. Outcome performance variables, such as success rate and response time, improved gradually across sessions, for each exercise. The level of participant interest also increased across sessions (p<0.001). All participants completed the program without experiencing any adverse effects. CONCLUSION: Substantial clinical and kinematic improvements were observed after applying a novel 3D ARS training program, suggesting that this system can enhance lower extremity function and facilitate assessments of lower extremity kinematic capacity. PMID- 26161354 TI - Ultrasonographic Diagnosis of Non-displaced Avulsion Fracture of the Acromion: A Case Report. AB - Avulsion fracture of the acromion is rare. It is difficult to diagnosis because there is little displacement and it occurs even without direct trauma. We experienced a case without direct trauma that was diagnosed with ultrasonography. A 55-year-old male patient visited our outpatient clinic with shoulder pain resulting from a significant stress at the trapezius muscle during lifting of a steel reinforcement. Simple radiography revealed a calcific deposit over the acromion rather than a fracture. Avulsion fracture was identified with ultrasonography. This is the first report demonstrating that ultrasonography has an advantage over radiographs in the diagnosis of an avulsion fracture of the acromion of the scapula. PMID- 26161355 TI - Churg-Strauss Syndrome as an Unusual Cause of Dysphagia: Case Report. AB - Systemic vasculitis is a rare disease, and the diagnosis is very difficult when patient shows atypical symptoms. We experienced an unusual case of dysphagia caused by Churg-Strauss syndrome with lower cranial nerve involvement. A 74-year old man, with a past history of sinusitis, asthma, and hearing deficiency, was admitted to our department for evaluation of dysphagia. He also complained of recurrent bleeding of nasal cavities and esophagus. Brain magnetic resonance imaging did not show definite abnormality, and electrophysiologic findings were suggestive of mononeuritis multiplex. Dysphagia had not improved after conventional therapy. Biopsy of the nasal cavity showed extravascular eosinophilic infiltration. All these findings suggested a rare form of Churg Strauss syndrome involving multiple lower cranial nerves. Dysphagia improved after steroid therapy. PMID- 26161356 TI - MEF2C-Related 5q14.3 Microdeletion Syndrome Detected by Array CGH: A Case Report. AB - Genetic screening is being widely applied to trace the origin of global developmental delay or intellectual disability. The 5q14.3 microdeletion has recently been uncovered as a clinical syndrome presenting with severe intellectual disability, limited walking ability, febrile convulsions, absence of speech, and minor brain malformations. MEF2C was suggested as a gene mainly responsible for the 5q14.3 microdeletion syndrome. We present the case of a 6 year-old girl, who is the first patient in Korea with de novo interstitial microdeletions involving 5q14.3, showing the typical clinical features of 5q14.3 microdeletion syndrome with a smaller size of chromosomal involvement compared to the previous reports. The microdeletion was not detected by subtelomeric multiplex ligation-dependent probe amplification, but by array comparative genomic hybridization, which is advisable for the detection of a small-sized genetic abnormality. PMID- 26161357 TI - Computed Tomography as an Objective Measurement Tool for Secondary Lymphedema Treated With Extracorporeal Shock Wave Therapy. AB - Two patients with stage three secondary lymphedema of the upper extremities underwent treatment for breast cancer, including surgery, chemotherapy, and radiotherapy. They were examined with computed tomography (CT) before and after extracorporeal shock wave therapy (ESWT). We used a manual tracing method using PiViewSTAR software to calculate the volume of the upper extremities. There was a decrease in the volume of the subcutaneous compartment measured by CT before and after ESWT. CT may be helpful in determining the treatment target area of ESWT and to monitor the effect of treatment by measuring the changes in volume before and after ESWT in patients with lymphedema. Therefore, CT may have good clinical potential for treatment and follow-up in the management of lymphedema. PMID- 26161358 TI - Novel Mutation of the GNE Gene Presenting Atypical Mild Clinical Feature: A Korean Case Report. AB - Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy is caused by mutations in GNE, a key enzyme in sialic acid biosynthesis. Here, we reported a case of GNE that presented with atypical mild clinical feature and slow progression. A 48-year-old female had a complaint of left foot drop since the age of 46 years. Electromyography (EMG) and muscle biopsy from left tibialis anterior muscle were compatible with myopathy. Genetic analysis led to the identification of c.1714G>C/c.527A>T compound heterozygous mutation, which is the second most frequent mutation in Japan as far as we know. Previous research has revealed that c.1714G>C/c.527A>T compound heterozygous mutation is a mild mutation as the onset of the disease is much later than the usual age of onset of GNE myopathy and the clinical course is slowly progressive. This was the first case report in Korea of the clinicopathological characteristics of GNE myopathy with GNE (c.1714G>C/c.527A>T compound heterozygous) mutation. PMID- 26161359 TI - Osteomyelitis of Bilateral Femoral Heads After Childbirth: A Case Report. AB - Hip and pelvic pain during pregnancy or after delivery is a common problem in young females, and in most cases this problem has a self-limiting course. The patient described in this case suffered from severe hip pain after childbirth. MR imaging study was performed and it showed arthritis of bilateral hip joints and osteomyelitis of femoral heads with an abscess in the surrounding muscle. Infection, such as septic arthritis or osteomyelitis, is an extremely rare cause of peripartum joint pain. The patient's clinical symptoms and laboratory findings improved with antibiotic therapy. However, limitation of motion of the bilateral hip joints persisted although the patient continued rehabilitative therapy for 15 months, and the patient had to undergo bilateral total hip replacement. Hereby, we present a case of severe osteomyelitis and pyogenic arthritis of bilateral femoral heads and hip joints after delivery, which eventually required bilateral total hip replacement. PMID- 26161360 TI - Cervical Meningomyelitis After Lumbar Epidural Steroid Injection. AB - Epidural steroid injections (ESI) are a common treatment for back pain management. ESI-related complications have increased with the growing number of procedures. We report a case of cervical meningomyelitis followed by multiple lumbar ESI. A 60-year-old male with diabetes mellitus presented to our hospital with severe neck pain. He had a history of multiple lumbar injections from a local pain clinic. After admission, high fever and elevated inflammatory values were detected. L-spine magnetic resonance imaging (MRI) revealed hematoma in the S1 epidural space. Antibiotic treatment began under the diagnosis of a lumbar epidural abscess. Despite the treatment, he started to complain of weakness in both lower extremities. Three days later, the weakness progressed to both upper extremities. C-spine MRI revealed cervical leptomeningeal enhancement in the medulla oblongata and cervical spinal cord. Removal of the epidural abscess was performed, but there was no neurological improvement. PMID- 26161362 TI - Mitochondrial Ca(2+) Remodeling is a Prime Factor in Oncogenic Behavior. AB - Cancer is sustained by defects in the mechanisms underlying cell proliferation, mitochondrial metabolism, and cell death. Mitochondrial Ca(2+) ions are central to all these processes, serving as signaling molecules with specific spatial localization, magnitude, and temporal characteristics. Mutations in mtDNA, aberrant expression and/or regulation of Ca(2+)-handling/transport proteins and abnormal Ca(2+)-dependent relationships among the cytosol, endoplasmic reticulum, and mitochondria can cause the deregulation of mitochondrial Ca(2+)-dependent pathways that are related to these processes, thus determining oncogenic behavior. In this review, we propose that mitochondrial Ca(2+) remodeling plays a pivotal role in shaping the oncogenic signaling cascade, which is a required step for cancer formation and maintenance. We will describe recent studies that highlight the importance of mitochondria in inducing pivotal "cancer hallmarks" and discuss possible tools to manipulate mitochondrial Ca(2+) to modulate cancer survival. PMID- 26161364 TI - Research Utilization among Nurses at a Teaching Hospital in Kenya. AB - INTRODUCTION: In the era of evidence based practice (EBP), health care delivery should be grounded on new or validated knowledge and evidence from research. The aim of the study was to assess research utilization by nurses and the influencing factors at Kenyatta National Hospital (KNH), the largest teaching hospital in Kenya. METHODS: The study employed a descriptive design that utilized both quantitative and qualitative methods of data collection. It incorporated the Barriers to Research Utilization Scale. It was conducted in six specialized care areas at KNH. Data was collected using questionnaires, Focus Group Discussion and in-depth interviews. Data was analyzed using SPSS version 13 and qualitative data analyzed using themes. RESULTS: The study found that 20.6% of the nurses were participating in research related to their work and 53.6% of these were implementing research findings to practice. Over 2/3 (70.5%) of the respondents were basing their evidence for practice on the knowledge gained during their nursing school. The three greatest barriers to research utilization were that research reports are not readily available (68.7%), unclear implications for practice (66.5%) and inadequate facilities for implementation (66.4%). CONCLUSION: It is recommended that sensitization trainings on nursing research/ utilization of findings in nursing practice be established to create awareness, motivate and enhance nurses' abilities and also facilities should be provided to enable implementation. PMID- 26161363 TI - Association between number of comorbid medical conditions and depression among individuals with diabetes; race and ethnic variations. AB - BACKGROUND: Medical and psychiatric comorbidities are commonly comorbid with diabetes. Race and ethnicity may, however, modify the link between medical and psychiatric comorbidities in individuals with diabetes. In this study we compared Non-Hispanic Whites, African Americans, and Caribbean Blacks with diabetes for the association between number of comorbid medical conditions and lifetime and 12 month major depressive disorder (MDD) in individuals with diabetes. METHODS: Data came from the National Survey of American Life (NSAL), 2001-2003. We included 603 patients with diabetes (75 non-Hispanic Whites, 396 African Americans, and 131 Caribbean Blacks). Number of comorbid medical conditions was the independent variable, lifetime and 12-month MDD were dependent variables, and age, gender, education, marital status, employment, and body mass index were covariates. Race- and ethnic- specific logistic regressions were used to determine race and ethnic differences in the associations between number of chronic medical conditions and lifetime and 12-month MDD, while the effect of all covariates were controlled. RESULTS: Number of chronic medical conditions was positively associated with lifetime MDD among non-Hispanic Whites (OR = 1.719, 95 % CI = 1.018 - 2.902) and African Americans (OR = 1.235, 95 % CI = 1.056- 1.445) but not Caribbean Blacks (P > .05). Number of chronic medical conditions was also associated with 12-month MDD among non-Hispanic Whites (OR = 1.757, 95 % CI = 1.119 - 2.759) and African Americans (OR = 1.381, 95 % CI = 1.175 - 1.623) but not Caribbean Blacks (P > .05). CONCLUSIONS: This study shows race- and ethnic- differences in the association between number of medical comorbidities and MDD among patients with diabetes. These findings invite researchers to study the mechanisms behind race- and ethnic- differences in vulnerability and resilience to the mental health effects of chronic medical conditions. PMID- 26161365 TI - The Effect of Ringer versus Haemaccel Preload on Incidence of Postoperative Nausea and Vomiting. AB - INTRODUCTION: Postoperative nausea and vomiting (PONV) is the most common and unpleasant postoperative complication. There is much controversy on preoperative fluid therapy. The aim of this study was to examine the effect of crystalloid fluid (Ringer solution) versus colloid (Haemaccel solution) on the incidence of postoperative nausea and vomiting in patients receiving spinal anesthesia. METHODS: In this double-blinded clinical trial, 46 patients were selected according to the inclusion and exclusion criteria. Patients were randomly allocated to one of two groups. The crystalloid group received Ringer solution at a volume of 7 ml/kg and colloid group received 7ml/kg of 3% Modified Gelatin (Haemaccel) as a preoperative intravenous bolus. We used a Verbal Rating Scale (VRS) for assessing the nausea and vomiting occurrence. Data were analyzed using SPSS software ver.13 and chi(2) test and independent t-test. RESULTS: The result showed that the incidence of PONV was less frequent in both Ringer and Haemaccel groups, but the incidence of vomiting and the intensity of nausea was not significantly different in any time point after anesthesia. CONCLUSION: We conclude that preoperative fluid administration decreases the incidence of PONV, and both Crystalloids (Ringer) and colloids (haemaccel) solution were found to be equivalent in prevention of PONV. Therefore using of either Ringer or haemaccel solution is recommended for prevention of PONV. PMID- 26161366 TI - "Discrimination", the Main Concern of Iranian Nurses over Inter-Professional Collaboration: an Explorative Qualitative Study. AB - INTRODUCTION: People in various professions may face discrimination. In the nursing field, discrimination among nurses in the workplace, regardless of race, gender or religion have not been studied; a problem that leads to a reduction in the quality of nursing care and nurse turnover. Discovery of the concerns of nurses about inter-professional collaboration is the purpose of this study. METHODS: The present study is conducted by using a qualitative content analysis. The data collection process included 22 unstructured and in-depth interviews with nurses between April 2012 and February 2013 in the medical teaching centers of Iran. A purposive sampling method was used. All interviews were recorded, typed, and analyzed simultaneously. RESULTS: The category obtained from explaining nurses' experiences of inter-professional collaboration was "discrimination" that included two subcategories, namely (1) lack of perspective towards equality in authorities, and (2) professional respect and value deficit. CONCLUSION: Nurses' experiences are indicating their perception of discrimination that influences the collaboration between nurses, which should be taken into account by managers. The findings of the present study help to managers about decision making on how to deal with staff and can be helpful in preventing nurse turnover and providing better services by nurses. PMID- 26161367 TI - Effect of Inhalation of Aroma of Geranium Essence on Anxiety and Physiological Parameters during First Stage of Labor in Nulliparous Women: a Randomized Clinical Trial. AB - INTRODUCTION: Anxiety increases significantly during labor, especially among nulliparous women. Such anxiety may affect the progress of labor and physiological parameters. The use of essential oils of aromatic plants, or aromatherapy, is a non-invasive procedure that can decrease childbirth anxiety. This study examined the effect of inhalation of the aroma of geranium essential oil on the level of anxiety and physiological parameters of nulliparous women in the first stage of labor. METHODS: In study, was carried out on 100 nulliparous women admitted to Bent al-Hoda Hospital in the city of Bojnord in North Khorasan province of Iran during 2012-2013. The women were randomly assigned to two groups of equal size, one experimental group (geranium essential oil) and one control (placebo) group. Anxiety levels were measured using Spielberger' questionnaire before and after intervention. Physiological parameters (systolic and diastolic blood pressure, respiratory rate, pulse rate) were also measured before and after intervention in both groups. Data analysis was conducted using the x2 test, paired t-test, Mann-Whitney U test, and Wilcox on test on SPSS 11.5. RESULTS: The mean anxiety score decreased significantly after inhalation of the aroma of geranium essential oil. There was also a significant decrease in diastolic blood pressure. CONCLUSION: Aroma of essential oil of geraniums can effectively reduce anxiety during labor and can be recommended as a non-invasive anti-anxiety aid during childbirth. PMID- 26161361 TI - Biosynthetic Machinery Involved in Aberrant Glycosylation: Promising Targets for Developing of Drugs Against Cancer. AB - Cancer cells depend on altered metabolism and nutrient uptake to generate and keep the malignant phenotype. The hexosamine biosynthetic pathway is a branch of glucose metabolism that produces UDP-GlcNAc and its derivatives, UDP-GalNAc and CMP-Neu5Ac and donor substrates used in the production of glycoproteins and glycolipids. Growing evidence demonstrates that alteration of the pool of activated substrates might lead to different glycosylation and cell signaling. It is already well established that aberrant glycosylation can modulate tumor growth and malignant transformation in different cancer types. Therefore, biosynthetic machinery involved in the assembly of aberrant glycans are becoming prominent targets for anti-tumor drugs. This review describes three classes of glycosylation, O-GlcNAcylation, N-linked, and mucin type O-linked glycosylation, involved in tumor progression, their biosynthesis and highlights the available inhibitors as potential anti-tumor drugs. PMID- 26161368 TI - Sexual Dysfunction and Help Seeking Behaviors in Newly Married Men in Sari City: a Descriptive. AB - INTRODUCTION: Sexual dysfunction is a major concern for people's general health. The aim of this study was to determine the status of sexual function and help seeking behaviors in newly married men. METHODS: This descriptive study was conducted on 363 newly married men. Simple random sampling was used according to premarital counseling offices in the health center of Sari city. Data collection instruments included personal and social characteristics, Arizona Sexual Experience Scale (ASEX), and help-seeking behaviors questionnaires. In order to determine the relationship between characteristics and sexual function, general linear model and also between socio-demographic characteristics and receiving or lack of receiving help, multivariate logistic regression test were used. RESULTS: The mean of sexual function score was 21.3 (2.7) out of possible 5-30, and 26% of men suffered sexual dysfunction. The highest prevalence (27.2%) of dysfunction was in the dimension of sexual stimulation, and the lowest (15.7%) in maintaining erection. For the treatment of sexual dysfunction, only 32% men had sought help, and 40% of them had visited specialists. The most frequent reasons for not seeking help were feeling uncomfortable with doctor, and their belief that doctor is not able to do much. 65% of men desired to be treated. CONCLUSION: The results demonstrated relatively high prevalence of sexual dysfunction among men, and unfortunately, most of them did not seek help for their sexual problem. Since Sexual dysfunction can leave damaging effects on the quality of life and marital relationship, interventions to deal with these challenges and screening to identify such problems appear necessary. PMID- 26161369 TI - Relationship between Health Promoting Lifestyle and Perceived Stress in Pregnant Women with Preeclampsia. AB - INTRODUCTION: Lifestyle during pregnancy has long-term effects on health of mother and child. Having previous illness or unexpected maternal or fetal conditions such as preeclampsia can complicate pregnancy and interfere with health-promoting behaviors and cause stress might interfere with health-promoting behaviors. This study was carried out to examine the relationship between health promoting lifestyles and perceived stress in women with preeclampsia. METHODS: This study is a descriptive correlation design that was conducted on 182 pregnant women with preeclampsia attending in the high risk clinics of Al-Zahra and Talegani hospitals in Tabriz 2014. Data gathering tools were three: demographics, health-promoting lifestyle (HPLP-II), and perceived stress questionnaires. SPSS Ver. 13 was used for data analysis. RESULTS: The mean (SD) of health promoting lifestyle among pregnant women with preeclampsia was 2.4 (0.4). Among the dimensions of health promoting life style, the highest mean score was for sub domain of nutrition, i.e. 2.8 (0.5), and the lowest score was achieved by the sub domains of physical activity, i.e. 1.5 (0.5).The mean (SD) score of perceived stress was 27.3 (7.1). There was reverse relationship between perceived stress and health -promoting behaviors. CONCLUSION: Based upon the results, health promoting behaviors were decreased by increment of perceived stress. Therefore, midwives can help women with preeclampsia by promoting health behaviors to reduce their stress and increase health-promoting behaviors. PMID- 26161370 TI - Design and Implementation Content Validity Study: Development of an instrument for measuring Patient-Centered Communication. AB - INTRODUCTION: The importance of content validity in the instrument psychometric and its relevance with reliability, have made it an essential step in the instrument development. This article attempts to give an overview of the content validity process and to explain the complexity of this process by introducing an example. METHODS: We carried out a methodological study conducted to examine the content validity of the patient-centered communication instrument through a two step process (development and judgment). At the first step, domain determination, sampling (item generation) and instrument formation and at the second step, content validity ratio, content validity index and modified kappa statistic was performed. Suggestions of expert panel and item impact scores are used to examine the instrument face validity. RESULTS: From a set of 188 items, content validity process identified seven dimensions includes trust building (eight items), informational support (seven items), emotional support (five items), problem solving (seven items), patient activation (10 items), intimacy/friendship (six items) and spirituality strengthening (14 items). Content validity study revealed that this instrument enjoys an appropriate level of content validity. The overall content validity index of the instrument using universal agreement approach was low; however, it can be advocated with respect to the high number of content experts that makes consensus difficult and high value of the S-CVI with the average approach, which was equal to 0.93. CONCLUSION: This article illustrates acceptable quantities indices for content validity a new instrument and outlines them during design and psychometrics of patient-centered communication measuring instrument. PMID- 26161371 TI - Clinical Implication of Colorectal Cancer Stem Cells: Still Has a Long Way to Go. PMID- 26161372 TI - ERCC1 and the Prognosis for Patients With Colon Cancer Receiving Oxaliplatin Based Adjuvant Chemotherapy. PMID- 26161373 TI - Stoma Creation After Surgery for Rectal Cancer: Temporary or Permanent? PMID- 26161374 TI - Aluminum Potassium Sulfate and Tannic Acid - A New Option for the Treatment of Grade 3 Hemorrhoids. PMID- 26161375 TI - Expression of the Cancer Stem Cell Markers CD44 and CD133 in Colorectal Cancer: An Immunohistochemical Staining Analysis. AB - PURPOSE: The aim of this study was to assess the expressions of CD44 and CD133 in colorectal cancer tissue by using immunohistochemical staining and to analyze the clinical significance of the expressions related to other clinicopathological data and survival results. METHODS: One hundred sixty-two patients with a biopsy proven colorectal adenocarcinoma who were operated on between January 1998 and August 2004 were enrolled in this study. Immunohistochemical staining for CD44 and CD133 was performed on primary colorectal cancer tissue, metastatic lymph nodes, and synchronous and metachronous metastatic tumor tissues if available. RESULTS: CD44 expression was stronger in the primary tumor than in metastatic lymph nodes (P < 0.001), and CD133 expression tended to be stronger in primary tumor than in metastatic lymph nodes (P = 0.057). No significant correlation was found between the CD44 and the CD133 expressions. The cases with recurrence showed low expression of CD44 (P = 0.017). CD133 expression was lower in cases with elevated CA 19-9 serum levels (P = 0.028) and advanced T stage (P = 0.038). Multivariate analysis proved that low expression of CD44 was an independent prognosis factor for short disease-free survival (P = 0.028). CONCLUSION: Low CD44 expression was correlated with increased tumor recurrence and short disease free survival, and low CD133 expression was associated with advanced tumor stage. We suggest that further studies be performed to evaluate whether the immunohistochemical method for determining the CD44 and the CD133 expressions is appropriate for exploring cancer stem-cell biology in patients with colorectal cancer. PMID- 26161376 TI - ERCC1 as a Predictive Marker for FOLFOX Chemotherapy in an Adjuvant Setting. AB - PURPOSE: The purpose of this study was to identify the excision repair cross complementation group 1 (ERCC1) as a predictive marker for FOLFOX adjuvant chemotherapy in stages II and III colon cancer patients. METHODS: A total of 166 high risk stages II and III colon cancer patients were retrospectively enrolled in this study, and data were collected prospectively. They underwent a curative resection followed by FOLFOX4 adjuvant chemotherapy. We analyzed ERCC1 expression in the primary colon tumor by using immunohistochemical staining. The oncological outcomes included the 5-year disease-free survival (DFS) rate. The DFS was analyzed by using the Kaplan-Meier method with the log-rank test. A Cox proportional hazard model was used for the prognostic analysis. RESULTS: ERCC1 positive expression was statistically significant in the older patients (P = 0.032). In the multivariate analysis, the prognostic factors for DFS were female sex (P = 0.016), N stage (P = 0.009), and postoperative carcinoembryonic antigen level (P = 0.001), but ERCC1 expression was not a statistically significant prognostic factor for DFS in the univariate analysis (P = 0.397). The 5-year DFS rate was not significantly associated with the ERCC1 expression in all patients (P = 0.396) or with stage III disease (P = 0.582). CONCLUSION: We found that ERCC1 expression was not significantly correlated with the 5-year DFS as reflected by the oncologic outcomes in patients with high-risk stages II and III colon cancer treated with FOLFOX adjuvant chemotherapy. PMID- 26161377 TI - Multivariate Analysis of Risk Factors Associated With the Nonreversal Ileostomy Following Sphincter-Preserving Surgery for Rectal Cancer. AB - PURPOSE: A loop ileostomy is used to protect an anastomosis after anal sphincter preserving surgery, especially in patients with low rectal cancer, but little information is available concerning risk factors associated with a nonreversal ileostomy. The purpose of this study was to identify risk factors of ileostomy nonreversibility after a sphincter-saving resection for rectal cancer. METHODS: Six hundred seventy-nine (679) patients with rectal cancer who underwent sphincter-preserving surgery between January 2004 and December 2011 were evaluated retrospectively. Of the 679, 135 (19.9%) underwent a defunctioning loop ileostomy of temporary intent, and these patients were divided into two groups, that is, a reversal group (RG, 112 patients) and a nonreversal group (NRG, 23 patients) according to the reversibility of the ileostomy. RESULTS: In 23 of the 135 rectal cancer patients (17.0%) that underwent a diverting ileostomy, stoma reversal was not possible for the following reasons; stage IV rectal cancer (11, 47.8%), poor tone of the anal sphincter (4, 17.4%), local recurrence (2, 8.7%), anastomotic leakage (1, 4.3%), radiation proctitis (1, 4.3%), and patient refusal (4, 17.4%). The independent risk factors of the nonreversal group were anastomotic leakage or fistula, stage IV cancer, local recurrence, and comorbidity. CONCLUSION: Postoperative complications such as anastomotic leakage or fistula, advanced primary disease (stage IV), local recurrence and comorbidity were identified as risk factors of a nonreversal ileostomy. These factors should be considered when drafting prudential guidelines for ileostomy closure. PMID- 26161378 TI - Comparison of Injection Sclerotherapy Between 5% Phenol in Almond Oil and Aluminum Potassium Sulfate and Tannic Acid for Grade 3 Hemorrhoids. AB - PURPOSE: Injection sclerotherapy for hemorrhoids has been performed for many years. Currently, 5% phenol in almond oil (PAO) and aluminum potassium sulfate and tannic acid (ALTA) are used as the agents. The purpose of this study was to compare the efficacy of the two agents. METHODS: A retrospective study was conducted involving 135 patients who underwent injection therapy for grade 3 hemorrhoids for the first time between 2013 and 2014 (PAO, 55 patients; ALTA, 80 patients). The efficacy was established as the proportion (%) of patients without symptoms such as hemorrhage and prolapse one year after treatment. We investigated four factors-sex, age, number of hemorrhoids, and agent-that might have an influence on the efficacy. RESULTS: The efficacies of ALTA and PAO one year after treatment were 75% and 20%, respectively. Only the agent was a significant independent factor (P < 0.01). CONCLUSION: The results suggest that ALTA is markedly more useful than PAO for injection sclerotherapy for grade 3 hemorrhoids. PMID- 26161379 TI - Inflammatory Fibroid Polyp in the Jejunum Causing Small Bowel Intussusception. AB - Intussusceptions are defined as the telescoping of one segment of the gastrointestinal tract into an adjacent distal segment. In the small bowel, intussusceptions are typically caused by benign processes, but can occasionally be caused by inflammatory fibroid polyps, which often present as intussusception and bowel obstruction. These polyps are rare, benign, tumorous lesions in the gastrointestinal tract and are typically observed in the stomach, but can occur anywhere in the gastrointestinal tract. Any case of a jejunojejunal intussusception caused by inflammatory fibroid polyps is considered rare, and we report the case of a 51-year-old woman with an inflammatory fibroid polyp of the jejunum presenting as an intussusception who was successfully treated with a resection. PMID- 26161380 TI - Intestinal Malrotation With a Fixed Partial Volvulus in an Adult. AB - A 44-year-old man had been suffering from nausea, vomiting and watery diarrhea for 5 days and was then admitted to Dankook University Hospital. He had suffered from several episodes of mild symptoms, including abdominal distension, loss of appetite, easy satiety, nausea, vomiting, and diarrhea throughout his lifetime, but most episodes had been ignored by him or physicians. An upper gastrointestinal series and a computed tomography scan revealed an intestinal malrotation with a volvulus. In order to untwist the small bowel in a counterclockwise direction to about 180 degrees, we had to perform not only a dissection of Ladd's band, but also a dissection of other adhesions between the mesocolon and the mesenteric vessel trunk. Surgical intervention needs to be performed for an old intestinal malrotation with any symptoms because the structural or morphological change proceeds as time passes, which is caused by fibrosis due to tension being repetitively applied to Ladd's band, leading to its contraction. Furthermore, a severe contraction may even lead to a fixed partial volvulus. PMID- 26161381 TI - Combined effect of bisphosphonate and recombinant human bone morphogenetic protein 2 on bone healing of rat calvarial defects. AB - BACKGROUND: This study aimed to investigate new bone formation using recombinant human bone morphogenetic protein 2 (rhBMP-2) and locally applied bisphosphonate in rat calvarial defects. METHODS: Thirty-six rats were studied. Two circular 5 mm diameter bony defect were formed in the calvaria using a trephine bur. The bony defect were grafted with Bio-Oss(r) only (group 1, n = 9), Bio-Oss(r) wetted with rhBMP-2 (group 2, n = 9), Bio-Oss(r) wetted with rhBMP-2 and 1 mM alendronate (group 3, n = 9) and Bio-Oss(r) wetted with rhBMP-2 and 10 mM alendronate (group 4, n = 9). In each group, three animals were euthanized at 2, 4 and 8 weeks after surgery, respectively. The specimens were then analyzed by histology, histomorphometry and immunohistochemistry analysis. RESULTS: There were significant decrease of bone formation area (p < 0.05) between group 4 and group 2, 3. Group 3 showed increase of new bone formation compared to group 2. In immunohistochemistry, collagen type I and osteoprotegerin (OPG) didn't show any difference. However, receptor activator of nuclear factor kappaB ligand (RANKL) decreased with time dependent except group 4. CONCLUSION: Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast. PMID- 26161382 TI - Peculiarity of Pharmaceutical Marketing in Serbia. PMID- 26161383 TI - Detection of Genomic Structural Variants from Next-Generation Sequencing Data. AB - Structural variants are genomic rearrangements larger than 50 bp accounting for around 1% of the variation among human genomes. They impact on phenotypic diversity and play a role in various diseases including neurological/neurocognitive disorders and cancer development and progression. Dissecting structural variants from next-generation sequencing data presents several challenges and a number of approaches have been proposed in the literature. In this mini review, we describe and summarize the latest tools - and their underlying algorithms - designed for the analysis of whole-genome sequencing, whole-exome sequencing, custom captures, and amplicon sequencing data, pointing out the major advantages/drawbacks. We also report a summary of the most recent applications of third-generation sequencing platforms. This assessment provides a guided indication - with particular emphasis on human genetics and copy number variants - for researchers involved in the investigation of these genomic events. PMID- 26161384 TI - Dysfunctional mitochondrial bioenergetics and the pathogenesis of hepatic disorders. AB - The liver is involved in a variety of critical biological functions including the homeostasis of glucose, fatty acids, amino acids, and the synthesis of proteins that are secreted in the blood. It is also at the forefront in the detoxification of noxious metabolites that would otherwise upset the functioning of the body. As such, this vital component of the mammalian system is exposed to a notable quantity of toxicants on a regular basis. It therefore comes as no surprise that there are over a hundred disparate hepatic disorders, encompassing such afflictions as fatty liver disease, hepatitis, and liver cancer. Most if not all of liver functions are dependent on energy, an ingredient that is primarily generated by the mitochondrion, the power house of all cells. This organelle is indispensable in providing adenosine triphosphate (ATP), a key effector of most biological processes. Dysfunctional mitochondria lead to a shortage in ATP, the leakage of deleterious reactive oxygen species (ROS), and the excessive storage of fats. Here we examine how incapacitated mitochondrial bioenergetics triggers the pathogenesis of various hepatic diseases. Exposure of liver cells to detrimental environmental hazards such as oxidative stress, metal toxicity, and various xenobiotics results in the inactivation of crucial mitochondrial enzymes and decreased ATP levels. The contribution of the latter to hepatic disorders and potential therapeutic cues to remedy these conditions are elaborated. PMID- 26161386 TI - Innovation in Laparoscopic Inguinal Hernia Reparation - Initial Experiences with the Parietex Progrip Laparoscopic(TM) - Mesh. AB - INTRODUCTION: The Laparoscopic TAPP (transabdominal pre-peritoneal inguinal hernia repair) - technique is becoming more widely and frequently used due to higher patient satisfaction and lower rates of both relapse and complications. MATERIALS AND METHODS: The role of the fixation of the mesh is especially important in regard to the endoscopic technique. The fixation of mesh through penetrating techniques using staples, clips, or screws is associated with a significantly increased risk of developing a chronic post-herniotomy inguinal pain syndrome (CPIP). In order to answer the question "fixation or no fixation of the mesh," the use of self-adhesive mesh is an optimal compromise. CONCLUSION: With the authors own operative technique consisting also of a standard pre- and post-operative management, the self-adhesive mesh was proven to be extremely reliable. As no specific materials to fix the mesh were needed, the method was fast, simple, and economical. We could also reduce the incidences of chronic inguinal pain in our patient population by using the self-adhesive mesh, without the risk of an increased recurrence rate in the observation period. PMID- 26161385 TI - Leukemogenic rearrangements at the mixed lineage leukemia gene (MLL)-multiple rather than a single mechanism. AB - Despite manifold efforts to achieve reduced-intensity and -toxicity regimens, secondary leukemia has remained the most severe side effect of chemotherapeutic cancer treatment. Rearrangements involving a short telomeric <1 kb region of the mixed lineage leukemia (MLL) gene are the most frequently observed molecular changes in secondary as well as infant acute leukemia. Due to the mode-of-action of epipodophyllotoxins and anthracyclines, which have widely been used in cancer therapy, and support from in vitro experiments, cleavage of this MLL breakpoint cluster hotspot by poisoned topoisomerase II was proposed to trigger the molecular events leading to malignant transformation. Later on, clinical patient data and cell-based studies addressing a wider spectrum of stimuli identified cellular stress signaling pathways, which create secondary DNA structures, provide chromatin accessibility, and activate nucleases other than topoisomerase II at the MLL. The MLL destabilizing signaling pathways under discussion, namely early apoptotic DNA fragmentation, transcription stalling, and replication stalling, may all act in concert upon infection-, transplantation-, or therapy induced cell cycle entry of hematopoietic stem and progenitor cells (HSPCs), to permit misguided cleavage and error-prone DNA repair in the cell-of-leukemia origin. PMID- 26161387 TI - NKG2D and DNAM-1 Ligands: Molecular Targets for NK Cell-Mediated Immunotherapeutic Intervention in Multiple Myeloma. AB - A pivotal strategy to improve NK cell-mediated antitumor activity involves the upregulation of activating ligands on tumor cells. Enhancement of NK cell mediated recognition of multiple myeloma cells was reported by us and others showing increased surface expression of NKG2D and DNAM-1 ligands on tumor cells following treatment with a number of chemotherapeutic agents, such as genotoxic drugs or inhibitors of proteasome, histone deacetylases, GSK3, and HSP-90. These compounds have the capability to affect tumor survival but also to activate specific transduction pathways associated with the upregulation of different NK cell activating ligands on the tumor cells. Here, we will summarize and discuss the molecular pathways whereby these drugs can regulate the expression of NK cell activating ligands in multiple myeloma cells. PMID- 26161388 TI - Comparison of Pentax-AWS Airwayscope and Glidescope for Infant Tracheal Intubation by Anesthesiologists during Cardiopulmonary Arrest Simulation: A Randomized Crossover Trial. AB - BACKGROUND: Recent guidelines for infant cardiopulmonary resuscitation emphasize that all rescuers should minimize interruption of chest compressions, even for endotracheal intubation. We compared the utility of the Pentax-AWS Airwayscope (AWS) with the Glidescope (GS) during chest compressions on an infant manikin. METHODS: Twenty-four anesthesiologists with more than two years of experience performed tracheal intubation on an infant manikin using the AWS and GS, with or without chest compressions. RESULTS: In GS trials, none of the participants failed without compressions, while three failed with compressions. In AWS trials, all participants succeeded regardless of chest compressions. Intubation time was significantly longer with chest compressions with the GS (P < 0.05), but not with the AWS. Difficulty of operation on a visual analog scale (VAS) for laryngoscopy did not increase significantly with chest compressions with either the GS or the AWS, while the VAS for tube passage through the glottis increased with compressions with the GS, but not with the AWS. CONCLUSION: We conclude that in infant simulations managed by anesthesiologists, the AWS performed better than the GS for endotracheal intubation with chest compressions. PMID- 26161389 TI - miR-451a Inhibited Cell Proliferation and Enhanced Tamoxifen Sensitive in Breast Cancer via Macrophage Migration Inhibitory Factor. AB - This study aims to investigate the regulative effects of microRNA-451a (miR-451a) on cell proliferation and sensitivity to tamoxifen in breast cancer cells. In cell culture experiments, the lentiviral vectors of pHBLV-miR-451a and pHBLV-miR 451a sponge were constructed and used to transfect MCF-7 and LCC2 cells. The transfection efficiency was tested by fluorescent observation, and cell lines with stable over- or downregulated expression of miR-451a were established. The expression of miR-451a and the target gene macrophage migration inhibitory factor (MIF) were detected by real-time reverse transcriptase polymerase chain reaction and/or western blot. Moreover, MTT assay, colony formation, and Transwell invasion assays were also performed. Data showed that the recombinant lentiviral vectors were constructed correctly, and the virus titer was 1 * 10(8) CFU/mL. The stable transfected cells were obtained. Overexpression of miR-451a downregulated MIF expression in mRNA and protein levels and inhibited cell proliferation, colony formation, and invasion of breast cancer cells. Downregulation of miR-451a upregulated MIF expression and increased breast cancer cell growth, invasion, and tamoxifen sensitivity. In summary, the miR-451a/MIF pathway may play important roles in the biological properties of breast cancer cells and may be a potential therapeutic target for breast cancer. PMID- 26161391 TI - Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients. AB - Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme(+) cells in CD8(+) lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8(+) lymphocytes may be stimulated by some kind of "nonself" cells in plaque positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma. PMID- 26161390 TI - Hereditary Syndromes Manifesting as Endometrial Carcinoma: How Can Pathological Features Aid Risk Assessment? AB - Endometrial carcinoma is the most common gynecological tumor worldwide. It can be the presenting malignancy, acting as the harbinger, of an undiagnosed hereditary syndrome. Up to 50% of females with Lynch syndrome present in this manner. Differentiation between Lynch, Muir-Torre, and Cowden syndromes can at times be challenging due to the overlapping features. Our review emphasizes on the strengths, pitfalls, and limitations of microscopic features as well as immunohistochemical and polymerase chain reaction- (PCR-) based tests used by laboratories to screen for DNA mismatch repair (MMR) and PTEN gene mutations in patients to enable a more targeted and cost effective approach in the use of confirmatory gene mutational analysis tests. This is crucial towards initiating timely and appropriate surveillance measures for the patient and affected family members. We also review the evidence postulating on the possible inclusion of uterine serous carcinoma as part of the spectrum of malignancies seen in hereditary breast and ovarian carcinoma syndrome, driven by mutations in BRCA1/2. PMID- 26161392 TI - Effect and Molecular Mechanisms of Traditional Chinese Medicine on Regulating Tumor Immunosuppressive Microenvironment. AB - Traditional Chinese medicine (TCM) is an important complementary strategy for treating cancer in China. The mechanism is related to regulating the internal environment and remodeling the tumor immunosuppressive microenvironment (TIM). Herein we illustrate how TIM is reformed and its protumor activity on promoting tumor cell proliferation, angiogenesis and lymphangiogenesis, tumor invasion, and the oncogenicity of cancer stem cells. Furthermore we summarize the effects and mechanism of TCM on regulating TIM via enhancing antitumor immune responses (e.g., regulating the expression of MHC molecules and Fas/FasL, attenuating cancerigenic ability of cancer stem cells) and remolding immunosuppressive cells (e.g., reversing immune phenotypes of T lymphocytes and tumor associated macrophages, promoting dendritic cells mature, restraining myeloid derived suppressor cells function, and regulating Th1/Th2 factors). We also reveal the bidirectional and multitargeting functions of TCM on regulating TIM. Hopefully, it provides new theoretical basis for TCM clinical practice in cancer treatment and prevention. PMID- 26161393 TI - The AirView Study: Comparison of Intubation Conditions and Ease between the Airtraq-AirView and the King Vision. AB - We conducted a study assessing the quality and speed of intubation between the Airtraq with its new iPhone AirView app and the King Vision in a manikin. The primary endpoint was reduction of time needed for intubation. Secondary endpoints included times necessary for intubation. 30 anaesthetists randomly performed 3 intubations with each device on a difficult airway manikin. Participants had a professional experience of 12 years: 60.0% possessed the Airtraq in their hospital, 46.7% the King Vision, and 20.0% both. Median time difference [IQR] to identify glottis (1.1 [-1.3; 3.9] P = 0.019), for tube insertion (2.1 [-2.6; 9.4] P = 0.002) and lung ventilation (2.8 [-2.4; 11.5] P = 0.001), was shorter with the Airtraq-AirView. Median time for glottis visualization was significantly shorter with the Airtraq-AirView (5.3 [4.0; 8.4] versus 6.4 [4.6; 9.1]). Cormack Lehane before intubation was better with the King Vision (P = 0.03); no difference was noted during intubation, for subjective device insertion or quality of epiglottis visualisation. Assessment of tracheal tube insertion was better with the Airtraq-AirView. The Airtraq-AirView allows faster identification of the landmarks and intubation in a difficult airway manikin, while clinical relevance remains to be studied. Anaesthetists assessed the intubation better with the Airtraq-AirView. PMID- 26161394 TI - The Effect of C-X-C Motif Chemokine 13 on Hepatocellular Carcinoma Associates with Wnt Signaling. AB - OBJECTS: To investigate the effect of CXCL13 (C-X-C motif chemokine 13) on hepatocellular carcinoma and clarify the potential mechanisms. METHODS: 32 patients with hepatocellular carcinoma and 12 healthy controls were recruited for analyzing the expression of CXCL13 by RT-PCR (reverse transcription-polymerase chain reaction). ELISA (enzyme-linked immune-sorbent assay) was used to test the concentration of serum CXCL13. The interaction between CXCL13 and Wnt signaling was analyzed by western blot. In vitro PBMCs cultured with HepG2 supernatant, the levels of IL-12, IL4, IL-6, and IL-17, and four IgG subclasses were detected by ELISA. RESULTS: The rate of high expression CXCL13 was 63.4% in advanced HCC patients, and the serum CXCL13 was also at a high level in stage IV HCC patients. Meanwhile CXCL13 level was positively correlated with serum ALT (Alanine Transaminase) and AST (Aspartate Aminotransferase). CXCL13 and Wnt/beta-catenin signaling shared a positive feedback loop. Furthermore, CXCL13 could obviously promote the expressions of IL-12 and IL-17, and induce IgG4 secreted by B cells. CONCLUSIONS: The effect of CXCL13 on promoting liver cancer is related to the activation of Wnt/beta-catenin pathway and the facilitation of IL-12, IL-17 and IgG4. CXCL13 plays an important role in the progression of HCC, and it may act as a potential target for the diagnosis and treatment of HCC. PMID- 26161395 TI - Expression of FOXP3, CD14, and ARG1 in Neuroblastoma Tumor Tissue from High-Risk Patients Predicts Event-Free and Overall Survival. AB - The prognosis of children with metastatic neuroblastoma (NB) > 18 months at diagnosis is dismal. Since the immune status of the tumor microenvironment could play a role in the history of disease, we evaluated the expression of CD45, CD14, ARG1, CD163, CD4, FOXP3, Perforin-1 (PRF1), Granzyme B (GRMB), and IL-10 mRNAs in primary tumors at diagnosis from children with metastatic NB and tested whether the transcript levels are significantly associated to event-free and overall survival (EFS and OS, resp.). Children with high expression of CD14, ARG1 and FOXP3 mRNA in their primary tumors had significantly better EFS. Elevated expression of CD14, and FOXP3 mRNA was significantly associated to better OS. CD14 mRNA expression levels significantly correlated to all markers, with the exception of CD4. Strong positive correlations were found between PRF1 and CD163, as well as between PFR1 and FOXP3. It is worth noting that the combination of high levels of CD14, FOXP3, and ARG1 mRNAs identified a small group of patients with excellent EFS and OS, whereas low levels of CD14 were sufficient to identify patients with dismal survival. Thus, the immune status of the primary tumors of high-risk NB patients may influence the natural history of this pediatric cancer. PMID- 26161396 TI - Polymorphisms of NFkappaB1 and IkappaBalpha and Their Synergistic Effect on Nasopharyngeal Carcinoma Susceptibility. AB - Nasopharyngeal carcinoma (NPC) is a multifactoral and polygenic disease with high prevalence in Southeast Asia and Southern China. Environmental factors and genetic susceptibility play important roles in NPC pathogenesis. In the present study, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in nuclear factor-kappa B (NFkappaB) and its inhibitor (IkappaBalpha) conferred consistent risks for NPC. Four putatively functional SNPs (NFkappaB1: rs28362491del>ins ATTG; NFkappaB2: rs12769316G>A; IkappaBalpha: rs2233406C>T and rs696G>A) were analyzed to evaluate their associations with NPC risk in total 1590 NPC cases and 1979 cancer-free controls. We found that the rs28362491 insATTG variants (ins/del + ins/ins) in NFkappaB1 conferred an increased risk of NPC (odds ratio [OR] = 1.30, 95% confidence interval [CI] = 1.09-1.55, and P = 2.80 * 10(-3)) compared with the del/del homozygous genotype. The rs696AA variant in IkappaBalpha had an increased risk of NPC (OR = 1.41, 95% CI = 1.20-1.66, and P = 2.28 * 10(-5)) by decreasing IkappaBalpha expression due to the modulation of microRNA hsa-miR-449a. Furthermore, both adverse genotypes of NFkappaB/IkappaBalpha and their interaction also exerted an increased risk on NPC. Taken together, Our findings indicated that genetic variants in NFkappaB1 (rs28362491del>ins ATTG) and IkappaBalpha (rs696G>A) and their synergistic effect might contribute to NPC predisposition. PMID- 26161397 TI - Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review. AB - Localized renal cell carcinoma (RCC) is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR) inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer) has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC. PMID- 26161398 TI - A Portable Gait Asymmetry Rehabilitation System for Individuals with Stroke Using a Vibrotactile Feedback. AB - Gait asymmetry caused by hemiparesis results in reduced gait efficiency and reduced activity levels. In this paper, a portable rehabilitation device is proposed that can serve as a tool in diagnosing gait abnormalities in individuals with stroke and has the capability of providing vibration feedback to help compensate for the asymmetric gait. Force-sensitive resistor (FSR) based insoles are used to detect ground contact and estimate stance time. A controller (Arduino) provides different vibration feedback based on the gait phase measurement. It also allows wireless interaction with a personal computer (PC) workstation using the XBee transceiver module, featuring data logging capabilities for subsequent analysis. Walking trials conducted with healthy young subjects allowed us to observe that the system can influence abnormality in the gait. The results of trials showed that a vibration cue based on temporal information was more effective than intensity information. With clinical experiments conducted for individuals with stroke, significant improvement in gait symmetry was observed with minimal disturbance caused to the balance and gait speed as an effect of the biofeedback. Future studies of the long-term rehabilitation effects of the proposed system and further improvements to the system will result in an inexpensive, easy-to-use, and effective rehabilitation device. PMID- 26161400 TI - Intratumoral Heterogeneity of MAGE-C1/CT7 and MAGE-C2/CT10 Expression in Mucosal Melanoma. AB - Mucosal melanoma is a rare disease, which differs from its cutaneous counterpart genetically and for its clinical behaviour. Moreover this is a heterogeneous disease based on the tissue of origin. As CT7 and CT10 are highly expressed in cutaneous melanoma and are immunogenic in this disease, we analysed their expression throughout the different subtypes of mucosal melanoma and tumor development. We detected a frequent expression of CT7 in primaries and corresponding metastases (55%) as well as for CT10 (30%). This expression resulted to be heterogeneous in the same tumor specimen and moreover influenced by the tissue of origin. Our results support the role of these antigens in immunotherapy for mucosal melanoma. PMID- 26161399 TI - The Effect of Park and Urban Environments on Coronary Artery Disease Patients: A Randomized Trial. AB - AIM: To test the hypothesis that walking in a park has a greater positive effect on coronary artery disease (CAD) patients' hemodynamic parameters than walking in an urban environment. METHODS: Twenty stable CAD patients were randomized into two groups: 30-minute walk on 7 consecutive days in either a city park or busy urban street. Wilcoxon signed-rank test was employed to study short-term (30 min) and cumulative changes (following 7 consecutive days of exposure) in resting hemodynamic parameters in different environments. RESULTS: There were no statistically significant differences in the baseline and peak exercise systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), exercise duration, or HR recovery in urban versus park exposure groups. Seven days of walking slightly improved all hemodynamic parameters in both groups. Compared to baseline, the city park group exhibited statistically significantly greater reductions in HR and DBP and increases in exercise duration and HR recovery. The SBP and DBP changes in the urban exposed group were lower than in the park exposed group. CONCLUSIONS: Walking in a park had a greater positive effect on CAD patients' cardiac function than walking in an urban environment, suggesting that rehabilitation through walking in green environments after coronary events should be encouraged. PMID- 26161401 TI - Stem Cell-Based Therapies in Chagasic Cardiomyopathy. AB - Chagas disease is caused by Trypanosoma cruzi and can lead to a dilated cardiomyopathy decades after the prime infection by the parasite. As with other dilated cardiomyopathies, conventional pharmacologic therapies are not always effective and as heart failure progresses patients need heart transplantation. Therefore alternative therapies are highly desirable and cell-based therapies have been investigated in preclinical and clinical studies. In this paper we review the main findings of such studies and discuss future directions for stem cell-based therapies in chronic chagasic cardiomyopathy. PMID- 26161402 TI - Percutaneous Transtracheal Jet Ventilation with Various Upper Airway Obstruction. AB - A "cannot-ventilate, cannot-intubate" situation is critical. In difficult airway management, transtracheal jet ventilation (TTJV) has been recommended as an invasive procedure, but specialized equipment is required. However, the influence of upper airway resistance (UAR) during TTJV has not been clarified. The aim of this study was to compare TTJV using a manual jet ventilator (MJV) and the oxygen flush device of the anesthetic machine (AM). We made a model lung offering variable UAR by adjustment of tracheal tube size that can ventilate through a 14 G cannula. We measured side flow due to the Venturi effect during TTJV, inspired tidal volume (TVi), and expiratory time under various inspiratory times. No Venturi effect was detected during TTJV with either device. With the MJV, TVi tended to increase in proportion to UAR. With AM, significant variations in TVi was not detected with changes in any UAR. In conclusion, UAR influenced forward flow of TTJV in the model lung. The influence of choked flow from the Venturi effect was minimal under all UAR settings with the MJV, but the AM could not deliver sufficient flow. PMID- 26161403 TI - Microvessels Density in Uterine Leiomyosarcoma. AB - Uterine leiomyosarcomas (LMS) are rare tumors typically presenting rapid growth and unfavorable outcome. Nowadays the results of uterine LMS treatment do not meet expectations. Angiogenesis is one of processes investigated to be target for future treatment. The aim of the research was to assess microvessels density (MVD) in tumor samples collected from 50 patients with histological confirmed uterine leiomyosarcoma and to investigate statistical relations between MVD, patients survival, and FIGO stage of tumor. The assessment was carried out using immunohistochemistry methods with anti-CD34 antibody. No significant difference in MVD between FIGO stages was observed. Furthermore, contrary to many other malignancies, we found no significant relation between MVD and patients overall and 2-year survival. Results obtained in the study suggest that processes on vascular mimicry and mesenchymal to epithelial transition (MET) may play important role in development of LMS. No statistical relation between MVD and survival leads to conclusion that not only angiogenesis but other mechanisms as well should be taken into consideration in planning future research. PMID- 26161404 TI - Anesthesia Related Toxic Effects on In Vitro Fertilization Outcome: Burden of Proof. AB - Management of pain and anxiety during oocyte retrieval makes anesthesia an important part of the in vitro fertilization (IVF) procedures. There are many studies investigating the influence of anesthesia on IVF success. This review article provides an overview of published data regarding the potential toxic effects of different anesthetic techniques (Loco-regional, general anesthesia (GA), and monitored anesthesia care (MAC)), different anesthetic agents, and alternative medicine approach (principally acupuncture) on the IVF outcome. From our analysis, evidence of serious toxicity in humans is not well established. Trials regarding different anesthetic techniques ended up without clear conclusions. Studies about GA came up with conflicting results. A few trials relate GA with lower pregnancy rates, although some others failed to prove this conclusion. Furthermore, detectable amounts of some anesthetic agents are measurable in the follicular fluid but these findings are not strongly associated with toxicity. MAC and Loco-regional anesthesia appear as safe alternative choices and there is evidence of improved outcome. Whereas acupuncture may provide assistance increasing IVF success according to some trials, some others could not obtain these effects. Questions about the appropriate time of application and the underlying mechanism of action are not answered yet, so further investigation should be done. PMID- 26161405 TI - Nontuberculous Mycobacteria: Epidemiologic, Mycobacteriologic, and Clinical Aspects. PMID- 26161406 TI - Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer. AB - Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics. PMID- 26161407 TI - Clinical Development of Immune Checkpoint Inhibitors. AB - Recent progress in cancer immunotherapy has been remarkable. Most striking are the clinical development and approval of immunomodulators, also known as immune checkpoint inhibitors. These monoclonal antibodies (mAb) are directed to immune checkpoint molecules, which are expressed on immune cells and mediate signals to attenuate excessive immune reactions. Although mAbs targeting tumor associated antigens, such as anti-CD20 mAb and anti-Her2 mAb, directly recognize tumor cells and induce cell death, immune checkpoint inhibitors restore and augment the antitumor immune activities of cytotoxic T cells by blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of immune checkpoint inhibitors in a variety of cancers. The first in class approved immune checkpoint inhibitor is ipilimumab, an anti-CTLA-4 (cytotoxic T lymphocyte antigen-4) mAb. Two pivotal phase III randomized controlled trials demonstrated a survival benefit in patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved ipilimumab for metastatic melanoma. Several clinical trials have since investigated new agents, alone and in combination, for various cancers. In this review, we discuss the current development status of and future challenges in utilizing immune checkpoint inhibitors. PMID- 26161409 TI - Cardioprotection during Adult and Pediatric Open Heart Surgery. PMID- 26161408 TI - Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study. AB - This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing >= 1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was >= 1.3. The null hypothesis was that <= 15% of patients gain such benefit. Overall, >= 1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1-6 (median: 4) actionable biomarkers per patient. After MP, patients received 1-4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was >= 1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC. PMID- 26161410 TI - Co-Designing Ambient Assisted Living (AAL) Environments: Unravelling the Situated Context of Informal Dementia Care. AB - Ambient assisted living (AAL) aims to help older persons "age-in-place" and manage everyday activities using intelligent and pervasive computing technology. AAL research, however, has yet to explore how AAL might support or collaborate with informal care partners (ICPs), such as relatives and friends, who play important roles in the lives and care of persons with dementia (PwDs). In a multiphase codesign process with six (6) ICPs, we envisioned how AAL could be situated to complement their care. We used our codesigned "caregiver interface" artefacts as triggers to facilitate envisioning of AAL support and unpack the situated, idiosyncratic context within which AAL aims to assist. Our findings suggest that AAL should be designed to support ICPs in fashioning "do-it yourself" solutions that complement tacitly improvised care strategies and enable them to try, observe, and adapt to solutions over time. In this way, an ICP could decide which activities to entrust to AAL support, when (i.e., scheduled or spontaneous) and how a system should provide support (i.e., using personalized prompts based on care experience), and when adaptations to system support are needed (i.e., based alerting patterns and queried reports). Future longitudinal work employing participatory, design-oriented methods with care dyads is encouraged. PMID- 26161411 TI - Airway Management of the Patient with Maxillofacial Trauma: Review of the Literature and Suggested Clinical Approach. AB - According to the Advanced Trauma Life Support recommendations for managing patients with life-threatening injuries, securing the airway is the first task of a primary caregiver. Airway management of patients with maxillofacial trauma is complex and crucial because it can dictate a patient's survival. Securing the airway of patients with maxillofacial trauma is often extremely difficult because the trauma involves the patient's airway and their breathing is compromised. In these patients, mask ventilation and endotracheal intubation are anticipated to be difficult. Additionally, some of these patients may not yet have been cleared of a cervical spine injury, and all are regarded as having a full stomach and having an increased risk of regurgitation and pulmonary aspiration. The requirements of the intended maxillofacial operation may often preclude the use of an oral intubation tube, and alternative methods for securing the airway should be considered before the start of the surgery. In order to improve the clinical outcome of patients with maxillofacial trauma, cooperation between maxillofacial surgeons, anesthesiologists, and trauma specialists is needed. In this review, we discuss the complexity and difficulties of securing the airway of patients with maxillofacial trauma and present our approach for airway management of such patients. PMID- 26161412 TI - Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43. AB - OBJECTS: To assess whether LNG exerts antiproliferation effects on human endometrial cells through changes of GJIC function and the phosphorylated Cx43. METHODS: Cell proliferation and apoptosis of human endometrial stromal cells (HESCs) and glandular cells (HEGCs) treated with LNG in a dose- and time dependent manner. GJIC change and further total Cx43 and serine 368 and 255 phosphorylated Cx43 were measured. RESULTS: 5 * 10(-5) mol/L LNG revealed a time dependent inhibition of cell proliferation and an increase of apoptosis in both HESCs and HEGCs. Furthermore, these cells demonstrated a significant GJIC enhancement upon treatment with 5 * 10(-5) mol/L for 48 hours. The effects of LNG were most noticeable in HESCs rather than in HEGCs. Associated with these changes, LNG induced a relative increase in total Cx43 in a time-dependent manner but not Ser368 phosphorylated Cx43. Moreover, laser scanning confocal microscope confirmed the increased expression of total Cx43 in the cytoplasm and, interestingly, the nuclear translocation of Ser255 phosphorylated Cx43. CONCLUSIONS: LNG likely inhibits the proliferation and promotes apoptosis in HESCs and HEGCs though an increase in gap junction permeability in vitro, which is achieved through the upregulation of Cx43 expression and the translocation of serine 255 phosphorylated Cx43 from the plasma to the nuclear compartment. PMID- 26161413 TI - Glycosyltransferases as Markers for Early Tumorigenesis. AB - BACKGROUND: Glycosylation is the most frequent posttranslational modification of proteins and lipids influencing inter- and intracellular communication and cell adhesion. Altered glycosylation patterns are characteristically observed in tumour cells. Normal and altered carbohydrate chains are transferred to their acceptor structures via glycosyltransferases. Here, we present the correlation between the presence of three different glycosyltransferases and tumour characteristics. METHODS: 235 breast cancer tissue samples were stained immunohistochemically for the glycosyltransferases N acetylgalactosaminyltransferase 6 (GALNT6), beta-1,6-N acetylglucosaminyltransferase 2 (GCNT2), and ST6 (alpha-N-acetyl-neuraminyl-2,3 beta-galactosyl-1,3)-N-acetylgalactosamine alpha-2,6-sialyltransferase 1 (ST6GALNac1). Staining was evaluated by light microscopy and was correlated to different tumour characteristics by statistical analysis. RESULTS: We found a statistically significant correlation for the presence of glycosyltransferases and tumour size and grading. Specifically smaller tumours with low grading revealed the highest incidences of glycosyltransferases. Additionally, Her4 expression but not pHer4-expression is correlated with the presence of glycosyltransferases. All other investigated parameters could not uncover any statistically significant reciprocity. CONCLUSION: Here we show, that glycosyltransferases can identify small tumours with well-differentiated cells; hence, glycosylation patterns could be used as a marker for early tumourigenesis. This assumption is supported by the fact that Her4 is also correlated to glycosylation, whereas the activated form of Her4 does not show such a connection with glycosylation. PMID- 26161414 TI - Beyond the Immune Suppression: The Immunotherapy in Prostate Cancer. AB - Prostate cancer (PCa) is the second most common cancer in men. As well in many other human cancers, inflammation and immune suppression have an important role in their development. We briefly describe the host components that interact with the tumor to generate an immune suppressive environment involved in PCa promotion and progression. Different tools provide to overcome the mechanisms of immunosuppression including vaccines and immune checkpoint blockades. With regard to this, we report results of most recent clinical trials investigating immunotherapy in metastatic PCa (Sipuleucel-T, ipilimumab, tasquinimod, Prostvac VF, and GVAX) and provide possible future perspectives combining the immunotherapy to the traditional therapies. PMID- 26161416 TI - Microbial Enzymes and Their Applications in Industries and Medicine 2014. PMID- 26161415 TI - A Bidimensional System of Facial Movement Analysis Conception and Reliability in Adults. AB - OBJECTIVE: To design a bidimensional facial movement measuring tool and study its reliability. METHODS: We utilized the free video-analysis software Kinovea that can track preselected points during movements and measure two-point distances off line. Three raters positioned facial markers on 10 healthy individuals and video taped them during maximal bilateral contractions of frontalis, corrugator, orbicularis oculi, zygomaticus, orbicularis oris, and buccinator, on two occasions. Each rater also analyzed the first video twice, one week apart. For each muscle, intrarater reliability was measured by percent agreements (PA) and intraclass correlation coefficients (ICC) between two assessments of the same video one week apart and between assessments of two videos collected one week apart. Interrater reliability was measured by PA, ICC, and coefficients of variation (CV) between assessments of the first video-recording by the three raters. RESULTS: Intrarater and interrater reliabilities were good to excellent for frontalis (PA and ICC > 70%; CV < 15%), moderate for orbicularis oculi, zygomaticus, and orbicularis oris, and poor for corrugator and buccinators. DISCUSSION: Without formal prior training, the proposed method was reliable for frontalis in healthy subjects. Improved marker selection, training sessions, and testing reliability in patients with facial paresis may enhance reliability for orbicularis oculi, zygomaticus, and orbicularis oris. PMID- 26161417 TI - Assessment of Movement Patterns during Intubation between Novice and Experienced Providers Using Mobile Sensors: A Preliminary, Proof of Concept Study. AB - BACKGROUND: There are likely marked differences in endotracheal intubation (ETI) techniques between novice and experienced providers. We performed a proof of concept study to determine if portable motion technology could identify the motion components of ETI between novice and experienced providers. METHODS: We recruited a sample of novice and experienced providers to perform ETIs on a cadaver. Their movements during ETI were recorded with inertial measurement units (IMUs) on the left wrist. The signals were assessed visually between novice and experienced providers to identify areas of differences at key steps during ETI. We then calculated spectral smoothness (SS), a quantitative measure inversely related to movement variability, for all ETI attempts. RESULTS: We enrolled five novice and five experienced providers. When visually inspecting the data, we noted maximum variability when inserting the blade of the laryngoscope into the mouth and while visualizing the glottic opening. Novice providers also had greater overall variability in their movement patterns (SS novice 6.4 versus SS experienced 26.6). CONCLUSION: Portable IMUs can be used to detect differences in movement patterns between novice and experienced providers in cadavers. Future ETI educational efforts may utilize portable IMUs to help accelerate the learning curve of novice providers. PMID- 26161418 TI - Which Metrics Are Appropriate to Describe the Value of New Cancer Therapies? AB - Patients with certain cancers are treated with curative intent, but for others the results are less favorable and different therapeutic approaches are needed. Early data suggest that new therapies, which modulate immune responses to cancers, may have potential for long-term survival in a proportion of cases. Therefore, it is timely to consider whether metrics generally used to describe the medical value of therapies for patients with common solid tumors remain appropriate for therapies with curative potential. Literature reviews were conducted to define how various stakeholders describe cure in oncology and to identify the endpoints used in clinical trials for selected solid tumors. The results showed that "cure" is described using various terms that can be divided broadly into lack of disease progression, eradication of cancerous cells, and survival. The review of trial endpoints showed frequent use of median overall survival (OS) and progression- and response-related endpoints. Because these endpoints were mainly described in the context of chemotherapies that are not generally curative, they may not adequately capture outcomes of new therapeutic modalities with potential for long-term survival. More appropriate endpoints may include mean OS, cure fraction, and OS rate at landmark time points. PMID- 26161419 TI - "Adherent" versus Other Isolation Strategies for Expanding Purified, Potent, and Activated Human NK Cells for Cancer Immunotherapy. AB - Natural killer (NK) cells have long been hypothesized to play a central role in the development of new immunotherapies to combat a variety of cancers due to their intrinsic ability to lyse tumor cells. For the past several decades, various isolation and expansion methods have been developed to harness the full antitumor potential of NK cells. These protocols have varied greatly between laboratories and several have been optimized for large-scale clinical use despite associated complexity and high cost. Here, we present a simple method of "adherent" enrichment and expansion of NK cells, developed using both healthy donors' and cancer patients' peripheral blood mononuclear cells (PBMCs), and compare its effectiveness with various published protocols to highlight the pros and cons of their use in adoptive cell therapy. By building upon the concepts and data presented, future research can be adapted to provide simple, cost-effective, reproducible, and translatable procedures for personalized treatment with NK cells. PMID- 26161420 TI - Clinical Usefulness of Immunohistochemical Staining of p57 kip2 for the Differential Diagnosis of Complete Mole. AB - OBJECTIVE: Can polymer-based immunohistochemical staining of p57(kip2) replace DNA analysis as an inexpensive means of differentiating complete mole from partial mole or hydropic abortion? METHODS AND MATERIALS: Original paraffin embedded tissue blocks from 14 equivocal cases were turned over to our laboratory and examined by immunohistochemical staining of p57(kip2). RESULTS: Four of the 14 cases showed clearly negative nuclear staining in cytotrophoblasts and villous stromal cells: these results were fully concordant with the control staining. The remaining 10 cases showed apparently positive staining in cytotrophoblasts and villous stromal cells. Without DNA analysis we are able to clearly differentiate the 4 cases of complete mole among the 14 equivocal cases. During follow-up, secondary low-risk gestational trophoblastic neoplasia (GTN) developed in 1 of the 4 cases of complete mole: the GTN was treated by single-agent chemotherapy. No subsequent changes were observed during follow-up in the other cases. CONCLUSION: Polymer-based immunohistochemical staining of p57(kip2) (paternally imprinted gene, expressed from maternal allele) is a very effective method that can be used to differentiate androgenetic complete mole from partial mole and hydropic abortion. We might be able to avoid the cost of DNA analysis. PMID- 26161421 TI - The Effects of Aquatic Exercises on Physical Fitness and Muscle Function in Dialysis Patients. AB - PURPOSE: The aim of this study was to assess the impact of a 3-month physical training program, conducted in an aquatic environment with end-stage renal disease patients (ESRD), on the physical fitness and functional parameters of the knee joint muscles. PATIENTS AND METHODS: The study included 20 ESDR patients with mean age 64.2 +/- 13.1 y. treated with hemodialysis in Dialysis Center of the University Hospital in Wroclaw. Before and 3 months after the physical training in water, a test was performed to evaluate the physical fitness of each patient; additionally, a measurement was taken of force-velocity parameters. The 3-month training program took place on nonhemodialysis days, in the recreational pool of the University of Physical Education in Wroclaw. RESULTS: After aquatic training cycle, an improvement was observed in all parameters measured using the Fullerton test. The value of peak torque and its relation to body mass increased in the movement of flexors and extensors of left and right lower extremities in all tested velocities. CONCLUSIONS: In assessing the physical fitness of studied women, the biggest improvement was achieved in tests assessing the strength of upper and lower extremities as well as lower body flexibility. Higher values of force-velocity parameters are conducive to women achieving better physical fitness test results. PMID- 26161422 TI - Molecular Phylogenetics 2014. PMID- 26161424 TI - A Randomized Comparison Simulating Face to Face Endotracheal Intubation of Pentax Airway Scope, C-MAC Video Laryngoscope, Glidescope Video Laryngoscope, and Macintosh Laryngoscope. AB - OBJECTIVES: Early airway management is very important for severely ill patients. This study aimed to investigate the efficacy of face to face intubation in four different types of laryngoscopes (Macintosh laryngoscope, Pentax airway scope (AWS), Glidescope video laryngoscope (GVL), and C-MAC video laryngoscope (C MAC)). METHOD: Ninety-five nurses and emergency medical technicians were trained to use the AWS, C-MAC, GVL and Macintosh laryngoscope with standard airway trainer manikin and face to face intubation. We compared VCET (vocal cord exposure time), tube pass time, 1st ventilation time, VCET to tube pass time, tube pass time to 1st ventilation time, and POGO (percentage of glottis opening) score. In addition, we compared success rate according to the number of attempts and complications. RESULT: VCET was similar among all laryngoscopes and POGO score was higher in AWS. AWS and Macintosh blade were faster than GVL and C-MAC in total intubation time. Face to face intubation success rate was lower in GVL than other laryngoscopes. CONCLUSION: AWS and Macintosh were favorable laryngoscopes in face to face intubation. GVL had disadvantage performing face to face intubation. PMID- 26161425 TI - A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF. AB - OBJECTIVE: To compare the effectiveness of a flexible multidose gonadotropin releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). STUDY DESIGN: A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. RESULTS: Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). CONCLUSION: The combination protocol does not provide additional efficacy. PMID- 26161423 TI - Human Tumor Antigens and Cancer Immunotherapy. AB - With the recent developments of adoptive T cell therapies and the use of new monoclonal antibodies against the immune checkpoints, immunotherapy is at a turning point. Key players for the success of these therapies are the cytolytic T lymphocytes, which are a subset of T cells able to recognize and kill tumor cells. Here, I review the nature of the antigenic peptides recognized by these T cells and the processes involved in their presentation. I discuss the importance of understanding how each antigenic peptide is processed in the context of immunotherapy and vaccine delivery. PMID- 26161426 TI - Comparisons of the Pentax-AWS, Glidescope, and Macintosh Laryngoscopes for Intubation Performance during Mechanical Chest Compressions in Left Lateral Tilt: A Randomized Simulation Study of Maternal Cardiopulmonary Resuscitation. AB - PURPOSE: Rapid advanced airway management is important in maternal cardiopulmonary resuscitation (CPR). This study aimed to compare intubation performances among Pentax-AWS (AWS), Glidescope (GVL), and Macintosh laryngoscope (MCL) during mechanical chest compression in 15 degrees and 30 degrees left lateral tilt. METHODS: In 19 emergency physicians, a prospective randomized crossover study was conducted to examine the three laryngoscopes. Primary outcomes were the intubation time and the success rate for intubation. RESULTS: The median intubation time using AWS was shorter than that of GVL and MCL in both tilt degrees. The time to visualize the glottic view in GVL and AWS was significantly lower than that of MCL (all P < 0.05), whereas there was no significant difference between the two video laryngoscopes (in 15 degrees tilt, P = 1; in 30 degrees tilt, P = 0.71). The progression of tracheal tube using AWS was faster than that of MCL and GVL in both degrees (all P < 0.001). Intubations using AWS and GVL showed higher success rate than that of Macintosh laryngoscopes. CONCLUSIONS: The AWS could be an appropriate laryngoscope for airway management of pregnant women in tilt CPR considering intubation time and success rate. PMID- 26161428 TI - Erratum. AB - [This corrects the article DOI: 10.1093/ofid/ofv024.][This corrects the article DOI: 10.1093/ofid/ofv023.][This corrects the article DOI: 10.1093/ofid/ofv018.][This corrects the article DOI: 10.1093/ofid/ofv022.]. PMID- 26161427 TI - Kinetics of Circulating Damage-Associated Molecular Patterns in Sepsis. AB - Circulating levels of conventional biomarkers and damage-associated molecular patterns were examined in 30 severe sepsis patients (20 survivors and 10 nonsurvivors). Plasma levels of interleukin 6, CRP, and procalcitonin reached their peaks on Day 0 (onset of sepsis) or Day 1 and declined rapidly thereafter despite the persistent severity. In contrast, elevated levels of histone H3, nucleosome, and high-mobility group protein Box 1 remained for longer periods of time. The peak level of histone H3 in the nonsurvivors was higher than that of the survivors (p < 0.05 on Day 7). The cutoff value of the histone H3 on Day 7 for death was 0.08 AU and the area under the receiver operating characteristic curve showed discriminative powers of 0.74. Measurement of circulating levels of the histone H3 provides additional information to that of the conventional indicators of inflammation for determining the severity of sepsis. PMID- 26161429 TI - Cellular plasticity regulated cancer stem cell niche: a possible new mechanism of chemoresistance. AB - The cancer stem cell (CSC) theory is an emerging concept that proposes a hierarchical nature of carcinogenesis, where a small number of tumor cells are capable of driving tumor growth. Despite many unanswered questions surrounding the cancer stem cell model, the hypothesis has rejuvenated hopes for formulating a novel therapeutic strategy for targeting the roots of cancer. This model predicts that cancer stem cells have the capacity to resist conventional radio- and chemotherapy and initiate disease recurrence. We recently investigated the mechanisms of chemoresistance in glioblastoma (GBM), the most common and aggressive adult human brain tumor. Exposure of patient derived glioma xenograft lines to a therapeutic dose of temolozolomide (TMZ), the most commonly used chemotherapy for patients with GBM, consistently increased the glioma stem cell (GSC) frequency over time. Lineage tracing analysis at the single sell level revealed unprecedented cellular plasticity within the glioma cells, allowing them to reprogram from a differentiated state to an undifferentiated CSC-like state. This reprogramming, mediated by cellular plasticity, is driven by TMZ-induced hypoxia inducible factors (HIFs), and provides a novel mechanism for chemoresistance acquisition. We herein discuss the possible role of temozolomide in regulating a cancer stem cell niche that supports GSC resistance, proliferation, and subsequent therapeutic relapse. PMID- 26161431 TI - ILAE type 3 hippocampal sclerosis in patients with anti-GAD-related epilepsy. AB - OBJECTIVE: To describe the neuropathologic findings and clinical course of 2 patients who underwent temporal lobectomy for medically refractive epilepsy and were later found to have high anti-glutamic acid decarboxylase (GAD) concentrations. METHODS: Small case series. RESULTS: Neuropathologic examination of both patients revealed International League Against Epilepsy (ILAE) type 3 hippocampal sclerosis. Following surgery, both developed signs and symptoms of stiff person syndrome and later cerebellar ataxia. Laboratory studies demonstrated high concentrations of anti-GAD antibodies in both patients. CONCLUSIONS: These cases suggest that ILAE type 3 hippocampal sclerosis may be immunologically related to and may exist as part of a broader anti-GAD-related neurologic syndrome in some instances. PMID- 26161430 TI - Complement activity is associated with disease severity in multifocal motor neuropathy. AB - OBJECTIVE: To investigate whether high innate activity of the classical and lectin pathways of complement is associated with multifocal motor neuropathy (MMN) and whether levels of innate complement activity or the potential of anti GM1 antibodies to activate the complement system correlate with disease severity. METHODS: We performed a case-control study including 79 patients with MMN and 79 matched healthy controls. Muscle weakness was documented with Medical Research Council scale sum score and axonal loss with nerve conduction studies. Activity of the classical and lectin pathways of complement was assessed by ELISA. We also determined serum mannose-binding lectin (MBL) concentrations and polymorphisms in the MBL gene (MBL2) and quantified complement-activating properties of anti-GM1 IgM antibodies by ELISA. RESULTS: Activity of the classical and lectin pathways, MBL2 genotypes, and serum MBL concentrations did not differ between patients and controls. Complement activation by anti-GM1 IgM antibodies was exclusively mediated through the classical pathway and correlated with antibody titers (p < 0.001). Logistic regression analysis showed that both high innate activity of the classical pathway of complement and high complement-activating capacity of anti GM1 IgM antibodies were significantly associated with more severe muscle weakness and axonal loss. CONCLUSION: High innate activity of the classical pathway of complement and efficient complement-activating properties of anti-GM1 IgM antibodies are determinants of disease severity in patients with MMN. These findings underline the importance of anti-GM1 antibody-mediated complement activation in the pathogenesis and clinical course of MMN. PMID- 26161432 TI - Cohabitation and Repartnering among Low-Income Black Mothers. AB - Serial cohabitation has increased dramatically in the U.S., especially in the low income Black population. The purpose of the study is to understand cohabiting and co-parenting relationships among unmarried cohabiting low-income urban Black families on their own terms, identifying the strengths, challenges, and unique needs of these families. Though cohabitation patterns varied widely, most participants had extensive periods living without a partner. This finding provides more support for the unbalanced marriage markets explanation than the serial cohabitation explanation. Indeed, most participants' children (83%) had none or only one resident father prior to the current cohabitation. Implications for having a new resident father and child development are discussed. PMID- 26161433 TI - Fast sorting of CD4+ T cells from whole blood using glass microbubbles. AB - The isolation of CD4 positive T lymphocyte (CD4+) from peripheral blood is important for monitoring patients after HIV infection. Here, we demonstrate a fast isolation strategy for CD4+ cells that involves mixing blood and glass microbubbles. After the specific binding of target cells to the microbubbles carrying specific antibodies on their surface, target cells will spontaneously float to the top of the blood vial and can be quickly separated. Using this strategy, we demonstrate that the isolation of CD4+ cells in less than 5 minutes and with better than 90% efficiency. This strategy for cell isolation based on buoyancy and glass microbubbles is quick and inexpensive, minimizes blood handling, does not require magnetic fields, or centrifugation equipment, and could lead to new, efficient strategies for AIDS diagnosis in resource-limited areas. PMID- 26161435 TI - Highly efficient retinal gene delivery with helper-dependent adenoviral vectors. AB - There have been significant advancements in the field of retinal gene therapy in the past several years. In particular, therapeutic efficacy has been achieved in three separate human clinical trials conducted to assess the ability of adeno associated viruses (AAV) to treat of a type of Leber's congenital amaurosis caused by RPE65 mutations. However, despite the success of retinal gene therapy with AAV, challenges remain for delivering large therapeutic genes or genes requiring long DNA regulatory elements for controlling their expression. For example, Stargardt's disease, a form of juvenile macular degeneration, is caused by defects in ABCA4, a gene that is too large to be packaged in AAV. Therefore, we investigated the ability of helper dependent adenovirus (HD-Ad) to deliver genes to the retina as it has a much larger transgene capacity. Using an EGFP reporter, our results showed that HD-Ad can transduce the entire retinal epithelium of a mouse using a dose of only 1 * 105 infectious units and maintain transgene expression for at least 4 months. The results demonstrate that HD-Ad has the potential to be an effective vector for the gene therapy of the retina. PMID- 26161434 TI - Lung gene therapy-How to capture illumination from the light already present in the tunnel. AB - Gene therapy has been considered as the most ideal medical intervention for genetic diseases because it is intended to target the cause of diseases instead of disease symptoms. Availability of techniques for identification of genetic mutations and for in vitro manipulation of genes makes it practical and attractive. After the initial hype in 1990s and later disappointments in clinical trials for more than a decade, light has finally come into the tunnel in recent years, especially in the field of eye gene therapy where it has taken big strides. Clinical trials in gene therapy for retinal degenerative diseases such as Leber's congenital amaurosis (LCA) and choroideremia demonstrated clear therapeutic efficacies without apparent side effects. Although these successful examples are still rare and sporadic in the field, they provide the proof of concept for harnessing the power of gene therapy to treat genetic diseases and to modernize our medication. In addition, those success stories illuminate the path for the development of gene therapy treating other genetic diseases. Because of the differences in target organs and cells, distinct barriers to gene delivery exist in gene therapy for each genetic disease. It is not feasible for authors to review the current development in the entire field. Thus, in this article, we will focus on what we can learn from the current success in gene therapy for retinal degenerative diseases to speed up the gene therapy development for lung diseases, such as cystic fibrosis. PMID- 26161437 TI - Hybrid Modified K-Means with C4.5 for Intrusion Detection Systems in Multiagent Systems. AB - Presently, the processing time and performance of intrusion detection systems are of great importance due to the increased speed of traffic data networks and a growing number of attacks on networks and computers. Several approaches have been proposed to address this issue, including hybridizing with several algorithms. However, this paper aims at proposing a hybrid of modified K-means with C4.5 intrusion detection system in a multiagent system (MAS-IDS). The MAS-IDS consists of three agents, namely, coordinator, analysis, and communication agent. The basic concept underpinning the utilized MAS is dividing the large captured network dataset into a number of subsets and distributing these to a number of agents depending on the data network size and core CPU availability. KDD Cup 1999 dataset is used for evaluation. The proposed hybrid modified K-means with C4.5 classification in MAS is developed in JADE platform. The results show that compared to the current methods, the MAS-IDS reduces the IDS processing time by up to 70%, while improving the detection accuracy. PMID- 26161436 TI - Amyloid burden, cortical thickness, and cognitive function in the Wisconsin Registry for Alzheimer's Prevention. AB - There is a growing interest in understanding how amyloid-beta (Abeta) accumulation in preclinical Alzheimer's disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively-normal (CN) individuals. Therefore, not much is known about the associations between Abeta burden, cortical thickness, and cognition in midlife. We examined this question in 109, CN, late-middle-aged adults (mean age=60.72+/-5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive exam. Blinded visual rating of the PiB scans was used to classify the participants as Abeta+ or Abeta-. Cortical thickness measurements were derived from the MR images. The Abeta+ group exhibited significant thinning of the entorhinal cortex and accelerated age associated thinning of the parahippocampal gyrus compared with the Abeta- group. The Abeta+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early Abeta aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Abeta deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought. PMID- 26161438 TI - A Multiconstrained Grid Scheduling Algorithm with Load Balancing and Fault Tolerance. AB - Grid environment consists of millions of dynamic and heterogeneous resources. A grid environment which deals with computing resources is computational grid and is meant for applications that involve larger computations. A scheduling algorithm is said to be efficient if and only if it performs better resource allocation even in case of resource failure. Allocation of resources is a tedious issue since it has to consider several requirements such as system load, processing cost and time, user's deadline, and resource failure. This work attempts to design a resource allocation algorithm which is budget constrained and also targets load balancing, fault tolerance, and user satisfaction by considering the above requirements. The proposed Multiconstrained Load Balancing Fault Tolerant algorithm (MLFT) reduces the schedule makespan, schedule cost, and task failure rate and improves resource utilization. The proposed MLFT algorithm is evaluated using Gridsim toolkit and the results are compared with the recent algorithms which separately concentrate on all these factors. The comparison results ensure that the proposed algorithm works better than its counterparts. PMID- 26161439 TI - Comment on "On Soft beta-Open Sets and Soft beta-Continuous Functions". PMID- 26161440 TI - Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates. AB - Tire derived aggregate (TDA) has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA) and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength) based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA. PMID- 26161442 TI - LIF is a new p53 negative regulator. AB - Leukemia inhibitory factor (LIF), a cytokine that belongs to the interleukin-6 family, regulates multiple important biological functions. Recently, we found that LIF is an important negative regulator of p53 in human colorectal cancer cells. LIF negatively regulates p53 protein levels and functions by activation of the Stat3 signaling pathway, which in turn induces the expression of ID1, the helix-loop-helix (HLH) protein inhibitor of differentiation and DNA binding. ID1 increases MDM2 expression at both mRNA and protein levels to accelerate p53 protein degradation. Overexpression of LIF increases chemoresistance of cultured colorectal cancer cells and colorectal xenograft tumors in a largely p53 dependent manner. Furthermore, LIF is overexpressed in a large percentage of human colorectal cancer specimens and LIF overexpression is associated with a poor prognosis in colorectal cancer patients. Our study revealed a new role of LIF in tumorigenesis through regulation of the p53 signaling pathway. PMID- 26161441 TI - Unraveling Cholesterol Catabolism in Mycobacterium tuberculosis: ChsE4-ChsE5 alpha2beta2 Acyl-CoA Dehydrogenase Initiates beta-Oxidation of 3-Oxo-cholest-4-en 26-oyl CoA. AB - The metabolism of host cholesterol by Mycobacterium tuberculosis (Mtb) is an important factor for both its virulence and pathogenesis, although how and why cholesterol metabolism is required is not fully understood. Mtb uses a unique set of catabolic enzymes that are homologous to those required for classical beta oxidation of fatty acids but are specific for steroid-derived substrates. Here, we identify and assign the substrate specificities of two of these enzymes, ChsE4 ChsE5 (Rv3504-Rv3505) and ChsE3 (Rv3573c), that carry out cholesterol side chain oxidation in Mtb. Steady-state assays demonstrate that ChsE4-ChsE5 preferentially catalyzes the oxidation of 3-oxo-cholest-4-en-26-oyl CoA in the first cycle of cholesterol side chain beta-oxidation that ultimately yields propionyl-CoA, whereas ChsE3 specifically catalyzes the oxidation of 3-oxo-chol-4-en-24-oyl CoA in the second cycle of beta-oxidation that generates acetyl-CoA. However, ChsE4 ChsE5 can catalyze the oxidation of 3-oxo-chol-4-en-24-oyl CoA as well as 3-oxo-4 pregnene-20-carboxyl-CoA. The functional redundancy of ChsE4-ChsE5 explains the in vivo phenotype of the igr knockout strain of Mycobacterium tuberculosis; the loss of ChsE1-ChsE2 can be compensated for by ChsE4-ChsE5 during the chronic phase of infection. The X-ray crystallographic structure of ChsE4-ChsE5 was determined to a resolution of 2.0 A and represents the first high-resolution structure of a heterotetrameric acyl-CoA dehydrogenase (ACAD). Unlike typical homotetrameric ACADs that bind four flavin adenine dinucleotide (FAD) cofactors, ChsE4-ChsE5 binds one FAD at each dimer interface, resulting in only two substrate-binding sites rather than the classical four active sites. A comparison of the ChsE4-ChsE5 substrate-binding site to those of known mammalian ACADs reveals an enlarged binding cavity that accommodates steroid substrates and highlights novel prospects for designing inhibitors against the committed beta oxidation step in the first cycle of cholesterol side chain degradation by Mtb. PMID- 26161443 TI - A chiral HPLC-MS/MS method for simultaneous quantification of warfarin enantiomers and its major hydroxylation metabolites of CYP2C9 and CYP3A4 in human plasma. AB - Warfarin is an oral anticoagulant that requires frequent therapeutic drug monitoring due to a narrow therapeutic window, considerable interindividual variability in drug response, and susceptibility to drug-drug and drug-diet interactions. Enantiomeric separation and quantification of warfarin enantiomers and clinically important major hydroxylation metabolites are essential for drug interaction studies and phenotypic characterization of CYP2C9 and CYP3A4, the major cytochrome P450 (CYP) enzymes involved in warfarin metabolism. Here, we describe the development and validation of a chiral high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based quantification of R warfarin, S-warfarin, S-7-hydroxywarfarin (the major CYP2C9 metabolite) and (9R;10S)-10-hydroxywarfarin (the CYP3A4 metabolite) in human plasma. Simple protein precipitation-based extraction showed good recovery of analytes (82.9 - 96.9%). The developed method exhibited satisfactory intra-day and inter-day accuracy and precision. The lower limits of detection were 0.25 nM (or ~0.08 ng/mL) for the warfarin enantiomers and 0.1 nM (or ~0.04 ng/mL) for S-7 hydroxywarfarin and (9R;10S)-10-hydroxywarfarin using only 50 uL plasma during extraction. The validated method was successfully applied to analyze plasma samples obtained from a healthy human subject who enrolled in a clinical drug interaction study involving warfarin. PMID- 26161444 TI - Special section: Conserving nature's stage. PMID- 26161445 TI - Preface. RNA Scaffolds. PMID- 26161446 TI - Collaborations: Recipe for a team. PMID- 26161447 TI - Substituent-Controlled Reversible Switching of Charge Injection Barrier Heights at Metal/Organic Semiconductor Contacts Modified with Disordered Molecular Monolayers. AB - Electrically stimulated switching of a charge injection barrier at the interface between an organic semiconductor and an electrode modified with a disordered monolayer (DM) is studied by using various benzenethiol derivatives as DM molecules. The switching behavior is induced by a structural change in the DM molecules and is manifested as a reversible inversion of the polarity of DM modified Au electrode/rubrene/DM-modified Au electrode diodes. The switching direction is found to be dominantly determined by the push-back effect of the thiol bonding group, while the terminal group modulates the switching strength. A device with 1,2-benzenedithiol DMs exhibited the highest switching ratios of 20, 10(2), and 10(3) for the switching voltages of 3, 5, and 7 V, respectively. A variation in the tilt angle of benzenethiol DMs due to the application of 7 V is estimated to be smaller than 23.6 degrees by model calculations. This study offers an understanding for obtaining highly stable operations of organic electronic devices, especially with molecular modification layers. PMID- 26161448 TI - Experimental determination of field factors ([Formula: see text]) for small radiotherapy beams using the daisy chain correction method. AB - Recently, Alfonso et al proposed a new formalism for the dosimetry of small and non-standard fields. The proposed new formalism is strongly based on the calculation of detector-specific beam correction factors by Monte Carlo simulation methods, which accounts for the difference in the response of the detector between the small and the machine specific reference field. The correct calculation of the detector-specific beam correction factors demands an accurate knowledge of the linear accelerator, detector geometry and composition materials. The present work shows that the field factors in water may be determined experimentally using the daisy chain correction method down to a field size of 1 cm * 1 cm for a specific set of detectors. The detectors studied were: three mini ionization chambers (PTW-31014, PTW-31006, IBA-CC01), three silicon-based diodes (PTW-60018, IBA-SFD and IBA-PFD) and one synthetic diamond detector (PTW-60019). Monte Carlo simulations and experimental measurements were performed for a 6 MV photon beam at 10 cm depth in water with a source-to-axis distance of 100 cm. The results show that the differences between the experimental and Monte Carlo calculated field factors are less than 0.5%-with the exception of the IBA-PFD-for field sizes between 1.5 cm * 1.5 cm and 5 cm * 5 cm. For the 1 cm * 1 cm field size, the differences are within 2%. By using the daisy chain correction method, it is possible to determine measured field factors in water. The results suggest that the daisy chain correction method is not suitable for measurements performed with the IBA-PFD detector. The latter is due to the presence of tungsten powder in the detector encapsulation material. The use of Monte Carlo calculated [Formula: see text] is encouraged for field sizes less than or equal to 1 cm * 1 cm for the dosimeters used in this work. PMID- 26161449 TI - Symptom Burden of Chronic Lung Disease Compared with Lung Cancer at Time of Referral for Palliative Care Consultation. AB - RATIONALE: A growing evidence base supports provision of palliative care services alongside life-prolonging care. Whereas palliative care processes have been implemented widely in the care of patients with lung cancer, the same is not true for patients with chronic, progressive lung disease. OBJECTIVES: To compare the symptom burden of chronic lung disease with that of lung cancer at the time of initial palliative care consultation. METHODS: Data were abstracted from the Carolinas Palliative Care Consortium's Quality Data Collection Tool, an electronic database used by seven academic and community palliative care practices in multiple states for quality improvement purposes. We analyzed data derived from first palliative care encounters collected during a 2-year period, including the primary diagnosis of chronic lung disease or lung cancer, unresolved symptoms, setting of initial palliative care encounter, Palliative Performance Scale status, and on that basis we estimated prognosis for survival. We compared key clinical variables between chronic lung disease and lung cancer using Kruskal-Wallis and chi(2) tests. MEASUREMENTS AND MAIN RESULTS: We identified 152 patients with lung cancer and 86 patients with chronic lung disease. Of the total sample, 53% were women and 87% were white. Patients with chronic lung disease were more likely than those with lung cancer to have the initial palliative care encounter occur in the intensive care unit (17% vs. 6%; P = 0.005) and less likely as an outpatient (20% vs. 56%; P < 0.0001). Patients with chronic lung disease were also less likely to have a high Palliative Performance Scale status (14% vs. 30%; P = 0.009) but more likely to have an estimated prognosis for survival longer than 6 months (51% vs. 28%; P = 0.002). The most prevalent symptoms were dyspnea (55% vs. 42%) and pain (40% vs. 52%), neither of which differed between groups (P = 0.08). CONCLUSIONS: Patients with chronic lung disease have symptom burdens similar to those of patients with lung cancer at the time of first palliative care encounter. Given the population burden of chronic lung disease and limitations in the palliative care workforce, attention should be focused on ensuring that pulmonologists are prepared to assess and manage the common palliative care needs of patients with chronic lung disease. PMID- 26161451 TI - Steroid Profiling by LC-MS/MS in Nonsecreting and Subclinical Cortisol-Secreting Adrenocortical Adenomas. AB - CONTEXT: Long-term follow-up studies revealed that patients with subclinical hypercortisolism (SH) due to adrenocortical adenomas have an increased incidence of cardiovascular diseases and mortality. No studies have yet investigated the steroid profile and its implications in patients with SH. OBJECTIVE: The objective of the study was to analyze the steroid profile by liquid chromatography-tandem mass spectrometry in sera from patients with unilateral adrenocortical adenomas. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at an outpatient clinic. PARTICIPANTS: Patients with adrenocortical adenomas (nonsecreting, n = 66; SH, n = 28) and 188 age- and sex matched controls drawn from the general population participated in the study. MAIN OUTCOME MEASURES: Cortisol, 21-deoxycortisol, 11-deoxycortisol, 17 hydroxyprogesterone, androstenedione, dehydroepiandrosterone, T, progesterone, 11 deoxycorticosterone, and corticosterone in the basal condition and after a 1-24 ACTH test, and clinical data were measured. RESULTS: Patients with SH showed lower basal and 1-24 ACTH-stimulated levels of dehydroepiandrosterone and androstenedione than those with nonsecreting adenomas and controls. T was also lower in SH females. Receiver-operating characteristic curves showed that androgens had good accuracy in predicting SH (sensitivity and specificity were 71% and 76% for dehydroepiandrosterone and 69% and 61% for androstenedione, respectively). Increased cortisol and reduced dehydroepiandrosterone levels were independently associated with increased waist circumference. Cortisol was also independently associated with increased number of cardiovascular risk factors in SH patients. After 1-24 ACTH stimulation, the SH patients also showed increased production of 21-deoxycortisol and 11-deoxycorticosterone. CONCLUSIONS: Liquid chromatography-tandem mass spectrometry steroid profile performed for the first time in sera from patients with adrenocortical adenomas showed impaired secretion of several steroids in SH patients. This fingerprint can help in better characterizing the functional status of these tumors. PMID- 26161450 TI - TNF Receptors Predict Hip Fracture Risk in the WHI Study and Fatty Acid Intake Does Not Modify This Association. AB - CONTEXT: Chronic inflammation may increase the risk of fracture, and omega-3 polyunsaturated fatty acids (PUFAs) may reduce fracture risk via down-regulation of inflammatory cytokine gene expression and other mechanisms. OBJECTIVE: We investigated associations between baseline samples of inflammatory markers, TNFalpha soluble receptors 1 and 2 (TNFalpha-sR1 and -sR2), and incident hip fracture. These associations were then tested for effect modification by dietary PUFA intake estimated by a baseline food frequency questionnaire. DESIGN AND SETTING: A nested case-control study was conducted among participants of the Women's Health Initiative Observational Study (ages, 50-79 y). Multivariable conditional logistic regression models were constructed to account for the paired design. PARTICIPANTS: This study sampled 400 pairs of hip fracture cases and controls without incident hip fracture, matched on age, year of enrollment, and menopausal hormone use. MAIN OUTCOME MEASURES: Odds ratio of hip fracture by quartile of TNF soluble receptors. RESULTS: The odds ratio of hip fracture comparing the highest to lowest quartiles was 2.24 (95% confidence interval, 1.05 4.79; P for linear trend, .048) for TNFalpha-sR1 and 2.83 (95% confidence interval, 1.34-5.99; P for linear trend, .011) for TNFalpha-sR2, adjusted for FRAX hip fracture score, nutritional variables, and selected factors impacting inflammation; there was a gradient of risk by increasing quartile in TNFalpha sR1. PUFA intake did not modify these associations. CONCLUSIONS: Women with the highest levels of TNFalpha-sR1 and TNFalpha-sR2 had a greater than 2-fold increased hip fracture risk, independent of other fracture risk factors. These associations did not differ by high vs low PUFA intake. PMID- 26161452 TI - Deciphering the Role of Vasopressin in Primary Aldosteronism. AB - CONTEXT: The role of vasopressin (AVP) in the pathophysiology of primary aldosteronism (PA) remains unclear. OBJECTIVES: The primary aim of this study was to investigate AVP secretion in PA by measuring the plasma concentration of copeptin (PCop), the C-terminal portion of provasopressin. The secondary aim was to assess renal sensitivity to AVP. DESIGN AND SETTING: This was a cross sectional study in a tertiary-care hospital. PROTOCOL: We recruited 115 patients with PA, 48 patients with essential hypertension (EH), and 108 normotensive healthy subjects (HS). Blood was sampled for biochemical and hormonal evaluations in fasting condition after 1-h rest in supine position. Osmolality was determined in 24-h urine. PCop was determined by immunoassay. MAIN OUTCOME MEASURE: The main outcome measure was adjusted difference in PCop between groups. RESULTS: After adjustment for sex, body mass index, systolic blood pressure, natremia, and kalemia, PCop was significantly higher in patients with PA than in HS (geometric mean ratio, 1.61; 95% confidence interval [CI], 1.26-2.06; P < .0001) and patients with EH (1.40; 95% CI, 1.08-1.82; P = .0070) PCop was positively correlated with natremia (P = .0094). Urine osmolality was significantly lower in patients with PA than in HS (0.82; 95% CI, 0.74-0.92; P = .0002) and 24-h urinary output was significantly higher in patients with PA than in HS (1.32; 95% CI, 1.11-1.56; P = .0005). The relationship between urine osmolality and PCop was shifted downward in patients with PA but was similar in patients with EH and HS, indicating peripheral resistance to AVP. CONCLUSION: PCop increases in patients with PA in response to an increase in natremia and a renal resistance phenomenon, indicating that AVP release is chronically stimulated in PA. PMID- 26161453 TI - Free 25(OH)D and the Vitamin D Paradox in African Americans. AB - CONTEXT: African Americans have a lower total serum 25-hydroxyvitamin D [25(OH)D] but superior bone health. This has been referred to as a paradox. A recent publication found that free serum 25(OH)D is the same in black and white individuals. However, the study was criticized because an indirect method was used to measure free 25(OH)D. A direct method has recently been developed. OBJECTIVE: We hypothesized that although total serum 25(OH)D is lower in African Americans, free serum 25(OH)D measured directly would not differ between races. DESIGN: White and black healthy postmenopausal women were matched for age and body mass index. Serum total 25(OH)D, PTH, 1,25-dihydroxyvitamin D, vitamin D binding protein (VDBP), and bone density were measured. Measurement of free 25(OH)D was carried out using an ELISA. SETTING: The study was conducted at an ambulatory research unit in a teaching hospital. OUTCOME: A cross-racial comparison of serum free 25(OH)D was performed. RESULTS: A propensity match resulted in the selection of a total of 164 women. Total 25(OH)D was lower in black women (19.5 +/- 4.7 vs 26.9 +/- 6.4 ng/mL), but a direct measurement of free 25(OH)D revealed almost identical values (5.25 +/- 1.2 vs 5.25 +/- 1.3 ng/mL) between races. VDBP was significantly lower in blacks when using a monoclonal-based ELISA but higher with a polyclonal-based ELISA. Serum PTH, 1,25 dihydroxyvitamin D, and bone density were higher in African Americans. CONCLUSIONS: Free serum 25(OH)D is the same across races despite the lower total serum 25(OH)D in black women. Results comparing VDBP between races using a monoclonal vs a polyclonal assay were discordant. PMID- 26161454 TI - Effects of Magnetic Field Cycle on the Polarization Transfer from Parahydrogen to Heteronuclei through Long-Range J-Couplings. AB - Hyperpolarization of (13)C carboxylate signals of metabolically relevant molecules, such as acetate and pyruvate, was recently obtained by means of ParaHydrogen Induced Polarization by Side Arm Hydrogenation (PHIP-SAH). This method relies on functionalization of the carboxylic acid with an unsaturated alcohol (side arm), hydrogenation of the unsaturated alcohol using parahydrogen, and polarization transfer to the target (13)C signal. In this case, parahydrogen protons are added three to four bonds away from the target (13)C nucleus, while biologically relevant molecules had been hyperpolarized, using parahydrogen, through hydrogenation of an unsaturated bond adjacent to the target (13)C signal. The herein reported results show that the same polarization level can be obtained on the (13)C carboxylate signal of an ester by means of addition of parahydrogen to the acidic or to the alcoholic moiety and successive application of magnetic field cycle (MFC). Experimental results are supported by calculations that allow one to predict that, upon accurate control of magnetic field strength and speed of the passages, more than 20% polarization can be achieved on the (13)C carboxylate resonance of the esters by means of side arm hydrogenation and MFC. PMID- 26161455 TI - Differential toxicity of gold-doxorubicin in cancer cells vs. cardiomyocytes as measured by real-time growth assays and fluorescence lifetime imaging microscopy (FLIM). AB - The kinetics of toxicity of doxorubicin (Dox) and gold nanoparticle-conjugated doxorubicin (Au-Dox) were investigated in cultured B16 melanoma cells and cardiomyocytes using real-time cell-growth imaging. Both bolus exposure and continuous exposure were used. Modeling of the growth curve dynamics suggested patterns of uptake and/or expulsion of the drug that were different for the different cell lines and exposures. Dox alone in B16 cells fit to a model of slow drug buildup, whereas Au-Dox fit to a pattern of initial high drug efficacy followed by a decrease. In cardiomyocytes, the best fit was to a model of increasing drug concentration which then began to decrease, consistent with breakdown of the doxorubicin in solution. Cardiomyocytes were more sensitive than B16 cells to Dox alone (IC50 123 +/- 2 nM vs. 270 +/- 2 nM with continuous exposure), but were dramatically less sensitive to Au-Dox (IC50 1 +/- 0.1 MUM vs. 58 +/- 5 nM with continuous exposure). Bolus exposure for 40 min led to significant cell death in B16 cells but not in cardiomyocytes. Fluorescence lifetime imaging (FLIM) showed different patterns of uptake of Au-Dox in the two cell types that explained the differential toxicity. While Au-Dox concentrated in the nuclei of B16 cells, it remained endosomal in cardiomyocytes. These results suggest that stable conjugates of nanoparticles to doxorubicin may be useful for treating resistant cancers while sparing healthy tissue. PMID- 26161456 TI - Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography. AB - Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood-brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P-gp/BCRP function in vivo but also highlight some challenges associated with this strategy. PMID- 26161457 TI - How Well-Informed Are Pension Scheme Members on Their Future Pension Benefits? Evidence from Ireland. AB - One part of the policy response in many countries to increasing pension coverage will be greater private provision on the part of individuals. This requires that individuals are well informed about pensions. In this article, we assess levels of knowledge of pensions using a representative sample of older Irish adults. We find that two-thirds of individuals enrolled in pension schemes do not know what amount will be paid out on retirement and/or whether the payments will be in the form of lump sums, monthly payments, or both. One policy implication is the need for increased information to be directed at certain groups, in particular, women and less educated people. More fundamentally, the results suggest that the mandatory elements in pension systems should be extended. PMID- 26161459 TI - Impact of CYP2C8*3 polymorphism on in vitro metabolism of imatinib to N-desmethyl imatinib. AB - 1. Imatinib is metabolized to N-desmethyl imatinib by CYPs 3A4 and 2C8. The effect of CYP2C8*3 genotype on N-desmethyl imatinib formation was unknown. 2. We examined imatinib N-demethylation in human liver microsomes (HLMs) genotyped for CYP2C8*3, in CYP2C8*3/*3 pooled HLMs and in recombinant CYP2C8 and CYP3A4 enzymes. Effects of CYP-selective inhibitors on N-demethylation were also determined. 3. A single-enzyme Michaelis-Menten model with autoinhibition best fitted CYP2C8*1/*1 HLM (n = 5) and recombinant CYP2C8 kinetic data (median +/- SD Ki = 139 +/- 61 uM and 149 uM, respectively). Recombinant CYP3A4 showed two-site enzyme kinetics with no autoinhibition. Three of four CYP2C8*1/*3 HLMs showed single-enzyme kinetics with no autoinhibition. Binding affinity was higher in CYP2C8*1/*3 than CYP2C8*1/*1 HLM (median +/- SD Km = 6 +/- 2 versus 11 +/- 2 uM, P=0.04). CYP2C8*3/*3 (pooled HLM) also showed high binding affinity (Km = 4 uM) and single-enzyme weak autoinhibition (Ki = 449 uM) kinetics. CYP2C8 inhibitors reduced HLM N-demethylation by 47-75%, compared to 0-30% for CYP3A4 inhibitors. 4. In conclusion, CYP2C8*3 is a gain-of-function polymorphism for imatinib N demethylation, which appears to be mainly mediated by CYP2C8 and not CYP3A4 in vitro in HLM. PMID- 26161458 TI - Framing new pathways in transformative exercise for individuals with existing and newly acquired disability. AB - PURPOSE: This paper describes a continuum of customized exercise options for people with an existing and newly acquired disability or diagnosis referred to as the Transformative Exercise Framework. BACKGROUND: The period directly after rehabilitation is a critical juncture where many individuals return to life with high rates of sedentary behavior. After rehabilitation discharge, people with newly acquired disability or diagnoses often never make the transition into usage of community-based exercise services that are tailored, safe and effective. METHODS: Narrative review. RESULTS: The Transformative Exercise Framework supports a patient-to-participant, rehab-to-wellness model that emphasizes a linkage between physical and occupational therapists and community-based exercise trainers. The four focus areas - Rehabilitation, Condition-specific Exercise, Fitness and Lifetime Physical Activity - emphasize a range of options for people with newly acquired disability and diagnoses, or for people with existing disability and/or chronic health conditions who have a new injury, secondary condition or are severely deconditioned. CONCLUSION: The concept of transformative exercise is to support people with disabilities and diagnoses with a seamless restore-improve-prevent continuum of programs and services. This continuum connects individuals to rehabilitation and exercise professionals in a dynamic framework, which maximizes the expertise of both sets of professionals and provides the most effective interventions to achieve the greatest gains in health and function and/or to avoid future health decline. Implications for Rehabilitation Patients discharged from rehabilitation should be transformed into participants in lifelong physical activity through a continuum of health services, which we refer to as Transformative Exercise. Transformative exercise is a continuum of individually tailored exercise strategies/programs that aims to improve the function of underperforming systems, which inhibit community and/or lifelong physical activity participation. The Transformative Exercise Framework can be used by a therapist or exercise trainer to design a program that maximizes performance and time and is based on a specific process for identifying short and long term goals. PMID- 26161460 TI - Miscibility and Langmuir Studies of the Interaction of E2 (279-298) Peptide Sequence of Hepatitis G Virus/GB Virus-C with Dipalmitoylphosphatidyl Choline and Dimiristoylphosphatidyl Choline Phospholipids. AB - Mixed monolayers of E2(279-298), a synthetic peptide belonging to the structural protein E2 of the GB virus C (GBV-C), formerly know as hepatitis G virus (HGV), and the phospholipids dipalmitoylphosphatidyl choline (DPPC) and dimiristoylphosphatidyl choline (DMPC),which differ in acyl chains length, were obtained at the A/W interface (monolayers of extension) in order to provide new insights on E2/phospholipids interaction. Analysis of the surface pressure-area isotherms, Brewster angle microscopy images, relative thickness, and mean areas per molecule has allowed us to establish the conditions under which the mixed components of the monolayer are miscible or immiscible and know how the level of the E2/phospholipid interaction varies with the composition of the mixed films, the surface pressure, and the hydrocarbon chains length of the phospholipids. The steric hindrance caused by the penetration of the polymer strands into the more or less ordered hydrocarbon chains of the phospholipids was suggested to explain the differences in the peptide interaction with the phospholipids studied. Therefore, the novelty of results obtained with the Langmuir film balance technique, supplemented with BAM images allow us to achieve a deeper understanding of the interaction. PMID- 26161461 TI - Development of Man-rGO for Targeted Eradication of Macrophage Ablation. AB - This study was aimed to develop and evaluate a smart nanosystem that targeted photothermal ablation of inflammatory macrophages in atherosclerotic plaque. Mannosylated-reduced graphene oxide (Man-rGO) was synthesized using three step procedures: (1) preparation of ox-GOs, (2) microwave-assisted synthesis of PEI rGOs, and (3) mannosylation of PEI-rGO using reductive amination reaction (Man rGOs). The zeta-potential of Man-rGO that signifies electrophoretic mobility of the charged surface was examined using Zetasizer Nano ZS. The effects of Man-rGO on the cell viability was evaluated using LDH assay and AlamarBlue assay. The targeting efficacy of Man-rGO was assessed using the cellular uptake rate by M2 polarized (i.e., which is induced by IL-4) macrophage. The effects of NOMela loaded in Man-rGO on the enhancement of phagocytosis were evaluated by examining the phagocytic clearance rate of zymosan-FITC particles. The microwave-assisted reduction of GOs was adapted for a facile synthesis of polyethylenimine-reduced GO (PEI-rGO). The mannose functionalization (Man-rGO) of PEI-rGO produced a greater number of amide linkages formed by reductive amination reaction between PEI-rGO and mannose. The zeta-potential of PEI-rGO was +30.6 +/- 3.3 mV, whereas that of Man-rGO was down to +13.1 +/- 3.8 mV upon interaction with mannose mainly due to the conjugation of mannose on the PEI-rGO surface. Near-infrared (NIR) irradiation increased the temperature of Man-rGO solution to around 45 degrees C, suggesting that Man-rGO is more potent than ox-GO or rGO in photothermal ablation activity triggered by NIR laser irradiation (808 nm). All testing formulations at the concentrations up to 10 MUg/mL exerted less than 10% of membrane disintegration. For AlamarBlue study, more than 90% of cell viability were maintained at the concentrations (up to 10 MUg/mL) of all tested formulations. The fluorescent microscopy images of cells after 1 h incubation demonstrated that Man-rGO were mainly accumulated at the subcellular level where the mannose receptors were overexpressed. The cell viability of macrophages significantly decreased upon exposure to Man-rGO irradiated with NIR, but no changes were observed from that of mast cells (for mast cells, 98.3 +/- 0.3%; for macrophages, 67.8 +/- 1.3%, p < 0.01), indicating that Man-rGO achieved enhanced targetability toward mannose receptor mediated cellular uptake. N Nitrosomelatonin (NOMela) loaded in macrophage exerted enhanced phagocytic activity. It was concluded that the enhanced photothermal ablation activity of Man-rGO triggered by NIR laser irradiation was mediated through their targetability toward overexpressed mannose receptor, a marker of M2-phenotype of macrophage. The results of this study supported that Man-rGO can serve as an efficient platform for the targeted therapy against atherosclerosis. PMID- 26161462 TI - Vacuum FTIR Observation on the Dynamic Hygroscopicity of Aerosols under Pulsed Relative Humidity. AB - A novel approach based on a combination of a pulse RH controlling system and a rapid scan vacuum FTIR spectrometer (PRHCS-RSVFTIR) was utilized to investigate dynamic hygroscopicity of two atmospheric aerosols: ammonium sulfate ((NH4)2SO4) and magnesium sulfate (MgSO4). In this approach, rapid-scan infrared spectra of water vapor and aerosols were obtained to determine relative humidity (RH) in sample cell and hygroscopic property of aerosols with a subsecond time resolution. Heterogeneous nucleation rates of (NH4)2SO4 were, for the first time, measured under low RH conditions (<35% RH). In addition, studies of MgSO4 aerosols revealed that water mass transport may be limited by different processes depending on RH values (surface limited at 40% < RH < 52% and bulk phase limited at RH < 40%). Furthermore, we are also the first to report water diffusion constants in micron size MgSO4 aerosols at very low RH values. Our results have shown that the PRHCS-RSVFTIR is well-suited for determination of hygroscopicity of atmospheric aerosols and water transport and nucleation kinetics of liquid aerosols. PMID- 26161463 TI - From Molecules to Surfaces: Radical-Based Mechanisms of Si-S and Si-Se Bond Formation on Silicon. AB - The derivatization of silicon surfaces can have profound effects on the underlying electronic properties of the semiconductor. In this work, we investigate the radical surface chemistry of silicon with a range of organochalcogenide reagents (comprising S and Se) on a hydride-terminated silicon surface, to cleanly and efficiently produce surface Si-S and Si-Se bonds, at ambient temperature. Using a diazonium-based radical initiator, which induces formation of surface silicon radicals, a group of organochalcogenides were screened for reactivity at room temperature, including di-n-butyl disulfide, diphenyl disulfide, diphenyl diselenide, di-n-butyl sulfide, diphenyl selenide, diphenyl sulfide, 1-octadecanethiol, t-butyl disulfide, and t-butylthiol, which comprises the disulfide, diselenide, thiol, and thioether functionalities. The surface reactions were monitored by transmission mode Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ionization mass spectrometry. Calculation of Si-Hx consumption, a semiquantitative measure of yield of production of surface-bound Si-E bonds (E = S, Se), was carried out via FTIR spectroscopy. Control experiments, sans the BBD diazonium radical initiator, were all negative for any evident incorporation, as determined by FTIR spectroscopy. The functional groups that did react with surface silicon radicals included the dialkyl/diphenyl disulfides, diphenyl diselenide, and 1-octadecanethiol, but not t-butylthiol, diphenyl sulfide/selenide, and di-n-butyl sulfide. Through a comparison with the rich body of literature regarding molecular radicals, and in particular, silyl radicals, reaction mechanisms were proposed for each. Armed with an understanding of the reaction mechanisms, much of the known chemistry within the extensive body of radical-based reactivity has the potential to be harnessed on silicon and could be extended to a range of technologically relevant semiconductor surfaces, such as germanium, carbon, and others. PMID- 26161464 TI - Thin Layer Ionophore-Based Membrane for Multianalyte Ion Activity Detection. AB - A concept is introduced that allows one to detect the activity of multiple ions simultaneously and selectively with a single ion-selective membrane. This is demonstrated with ~300 nm thin plasticized PVC membranes containing up to two ionophores in addition to a lipophilic cation-exchanger, overlaid on an electropolymerized poly-3-octylthiophene (POT) film as the electron to ion transducer. The ion-selective membranes are formulated under ionophore depleted conditions (avoiding excess of ionophore over ion-exchanger), which is purposely different from common practice with ion-selective electrodes. Cyclic voltammetry is used to interrogate the films. An anodic scan partially oxidizes the POT underlayer, which results in the expulsion of cations from the membrane at an appropriate potential. During the scan of a membrane containing multiple ionophores, the least bound ion is expelled first, giving distinct Gaussian peak shaped ion transfer voltammetric waves that are analyzed in terms of their peak potential. These potentials are found to change with the logarithm of the ion activity, in complete analogy to ion-selective electrodes, and multiple such waves are observed with multiple ionophores that exhibit no obvious interference from the other ionophores present in the membrane. The concept is established with lithium and calcium ionophores and accompanied by a response model that assumes complete equilibration of the membrane at every applied potential. On the basis of the model, diffusion coefficients in the membrane or aqueous phase bear no influence on the peak potentials as long as thin layer behavior is observed, further confirming the analogy to a potentiometric experiment. Idealized ion transfer waves are narrower than experimental findings, which is explained by a broader than expected anodic peak for the oxidation of conducting polymer. The correspondence between experiment and theory is otherwise excellent in terms of thin layer behavior and Nernstian shift of the peaks with analyte concentration. PMID- 26161465 TI - Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease. AB - OBJECTIVE: The development of gliadin-specific antibody and T-cell responses were longitudinally monitored in young children with genetic risk for celiac disease (CD). MATERIAL AND METHODS: 291 newborn children positive for HLA-DQB1*02 and DQA1*05 alleles were followed until 3-4 years of age by screening for tissue transglutaminase autoantibodies (tTGA) by using a commercial ELISA-based kit and antibodies to deamidated gliadin peptide (anti-DGP) by an immunofluorometric assay. Eighty-five of the children were also followed for peripheral blood gliadin-specific CD4(+) T-cell responses by using a carboxyfluorescein diacetate succinimidyl ester-based in vitro proliferation assay. RESULTS: The cumulative incidence of tTGA seropositivity during the follow-up was 6.5%. CD was diagnosed in nine of the tTGA-positive children (3.1%) by duodenal biopsy at a median 3.5 years of age. All of the children with confirmed CD were both IgA and IgG anti DGP positive at the time of tTGA seroconversion and in over half of the cases IgG anti-DGP positivity even preceded tTGA seroconversion. Peripheral blood T-cell responses to deamidated and native gliadin were detected in 40.5% and 22.2% of the children at the age of 9 months and these frequencies decreased during the follow-up to the levels of 22.2% and 8.9%, respectively. CONCLUSIONS: Anti-DGP antibodies may precede tTGA seroconversion and thus frequent monitoring of both tTGA and anti-DGP antibodies may allow earlier detection of CD in genetically susceptible children. Peripheral blood gliadin-specific T-cell responses are relatively common in HLA-DQ2-positive children and are not directly associated with the development of CD. PMID- 26161466 TI - The Association of Intelligence, Visual-Motor Functioning, and Personality Characteristics With Adaptive Behavior in Individuals With Williams Syndrome. AB - Williams syndrome (WS) is associated with deficits in adaptive behavior and an uneven adaptive profile. This study investigated the association of intelligence, visual-motor functioning, and personality characteristics with the adaptive behavior in individuals with WS. One hundred individuals with WS and 25 individuals with developmental disabilities of other etiologies were included in this study. This study found that IQ and visual-motor functioning significantly predicted adaptive behavior in individuals of WS. Visual-motor functioning especially predicted the most amount of unique variance in overall adaptive behavior and contributed to the variance above and beyond that of IQ. Present study highlights the need for interventions that address visual-motor and motor functioning in individuals with WS. PMID- 26161467 TI - Reliability and Validity of the Pediatric Quality of Life Inventory With Individuals With Intellectual and Developmental Disabilities. AB - The Pediatric Quality of Life Inventory (PedsQL) measures health-related quality of life, a growing area of research, particularly among individuals with disabilities. This research is necessary to fully understand the varied needs of the population and, ultimately, ensure that those needs are being met. The current study assessed the reliability and validity of the PedsQL in individuals with intellectual and developmental disabilities, including individuals with autism spectrum disorder. Participants included 359 caregivers of children, youth, and young adults with IDD. Caregivers completed the PedsQL 4.0 Generic Core Scales questions regarding the individual's physical health and the Strengths and Difficulties Questionnaire. The PedsQL achieved excellent reliability across scales, and distinguished healthy individuals from those with chronic health conditions, as well as individuals with ASD from those without. Factor analysis confirmed a 5-factor model, with moderate to high criterion validity. The PedsQL shows sound psychometric properties and may be a useful tool to measure psychosocial functioning in this population. PMID- 26161469 TI - Beneficial Effects of Long-Term Growth Hormone Treatment on Adaptive Functioning in Infants With Prader-Willi Syndrome. AB - The aim of this study was to investigate the effect of growth hormone treatment on adaptive functioning in children with Prader-Willi syndrome. Vineland Adaptive Behavior Scale (VABS) was assessed during a randomized controlled trial (RCT) and after 7 years of growth hormone treatment. In the RCT, 75 children (42 infants and 33 prepubertal children) with Prader-Willi syndrome were included. Subsequently, 53 children were treated with long-term growth hormone. Our study demonstrates a marked delay in adaptive functioning in infants and children with Prader-Willi syndrome, which was associated with older age and lower intelligence. Results of the repeated measurements show that the earlier growth hormone treatment was started during infancy, the better the adaptive skills were on the long-term. PMID- 26161468 TI - Why Dose Frequency Affects Spoken Vocabulary in Preschoolers With Down Syndrome. AB - In an earlier randomized clinical trial, daily communication and language therapy resulted in more favorable spoken vocabulary outcomes than weekly therapy sessions in a subgroup of initially nonverbal preschoolers with intellectual disabilities that included only children with Down syndrome (DS). In this reanalysis of the dataset involving only the participants with DS, we found that more therapy led to larger spoken vocabularies at posttreatment because it increased children's canonical syllabic communication and receptive vocabulary growth early in the treatment phase. PMID- 26161470 TI - Implicit Discrimination of Basic Facial Expressions of Positive/Negative Emotion in Fragile X Syndrome and Autism Spectrum Disorder. AB - Fragile X syndrome (FXS) and autism spectrum disorders (ASD) are characterized by impaired social functioning. We examined the spontaneous discrimination of happy and disgusted facial expressions, from neutral faces, in individuals with FXS (n = 13, Mage = 19.70) and ASD (n = 15, Mage = 11.00) matched on adaptive behavior and verbal abilities measured by the Vineland Adaptive Behavior Scale. Eye gaze to the eyes and mouth of neutral faces was also measured. Results suggest individuals with FXS and ASD distinguish facial expressions spontaneously in the same way. Individuals with FXS looked significantly less at the eye region of neutral faces than individuals with ASD. These results provide insight into similarities and differences in face processing in two neurodevelopmental disorders noted for their similarities in social behavior. PMID- 26161471 TI - Reconceptualizing Family Adaptation to Developmental Delay. AB - This study explores accurate conceptualization of the adaptation construct in families of children with developmental delay aged 3 to 8 years. Parents' self reported measures of adaptation and observed dyadic relationship variables were examined. Confirmatory factor analysis and longitudinal growth modeling were used to evaluate the nature of adaptational processes. Results indicate that adaptational processes vary across adaptation index, child developmental level, and parent gender. Adaptation indices did not load onto a single construct at any time point. Several adaptational processes remained stable across time, although others showed linear or quadratic change. The findings of the current study indicate that it is time for a change in how adaptation is conceived for families of children with developmental delay. PMID- 26161474 TI - Perceptions of final-year nursing students on the facilities, resources and quality of education provided by schools in Turkey. AB - The purpose of this study is to determine the perceptions of final-year nursing students regarding the adequacy of education, resources and internships in preparation for graduation. The study design was a descriptive cross-sectional study of nursing students (n: 1804) in their final year of education and questionnaires were used to collect data. Information related to student-to instructor ratios and internships was obtained from each institution. Most students reported receiving instruction or supervision by lecturers and clinicians who did not specialise in the field. Overall, students did not find the facilities, educational or technological resources and the quality of education offered by their respective schools adequate. The proportion of students who found the level of theoretical education, clinical practice and instructor support adequate was higher in state university colleges of nursing/faculties of health sciences than in state university schools of health sciences. PMID- 26161476 TI - The Molecular Epidemiology and Genetic Environment of Carbapenemases Detected in Africa. AB - Research articles describing carbapenemases and their genetic environments in Gram-negative bacteria were reviewed to determine the molecular epidemiology of carbapenemases in Africa. The emergence of resistance to the carbapenems, the last resort antibiotic for difficult to treat bacterial infections, affords clinicians few therapeutic options, with a resulting increase in morbidities, mortalities, and healthcare costs. However, the molecular epidemiology of carbapenemases throughout Africa is less described. Research articles and conference proceedings describing the genetic environment and molecular epidemiology of carbapenemases in Africa were retrieved from Google Scholar, Scifinder, Pubmed, Web of Science, and Science Direct databases. Predominant carbapenemase genes so far described in Africa include the blaOXA-48 type, blaIMP, blaVIM, and blaNDM in Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter spp., and Escherichia coli carried on various plasmid types and sizes, transposons, and integrons. Class D and class B carbapenemases, mainly prevalent in A. baumannii, K. pneumoniae, E. cloacae, Citrobacter spp., and E. coli were the commonest carbapenemases. Carbapenemases are mainly reported in North and South Africa as under-resourced laboratories, lack of awareness and funding preclude the detection and reporting of carbapenemase-mediated resistance. Consequently, the true molecular epidemiology of carbapenemases and their genetic environment in Africa is still unknown. PMID- 26161475 TI - Entry of Francisella tularensis into Murine B Cells: The Role of B Cell Receptors and Complement Receptors. AB - Francisella tularensis, the etiological agent of tularemia, is an intracellular pathogen that dominantly infects and proliferates inside phagocytic cells but can be seen also in non-phagocytic cells, including B cells. Although protective immunity is known to be almost exclusively associated with the type 1 pathway of cellular immunity, a significant role of B cells in immune responses already has been demonstrated. Whether their role is associated with antibody-dependent or antibody-independent B cell functions is not yet fully understood. The character of early events during B cell-pathogen interaction may determine the type of B cell response regulating the induction of adaptive immunity. We used fluorescence microscopy and flow cytometry to identify the basic requirements for the entry of F. tularensis into B cells within in vivo and in vitro infection models. Here, we present data showing that Francisella tularensis subsp. holarctica strain LVS significantly infects individual subsets of murine peritoneal B cells early after infection. Depending on a given B cell subset, uptake of Francisella into B cells is mediated by B cell receptors (BCRs) with or without complement receptor CR1/2. However, F. tularensis strain FSC200 DeltaiglC and DeltaftdsbA deletion mutants are defective in the ability to enter B cells. Once internalized into B cells, F. tularensis LVS intracellular trafficking occurs along the endosomal pathway, albeit without significant multiplication. The results strongly suggest that BCRs alone within the B-1a subset can ensure the internalization process while the BCRs on B-1b and B-2 cells need co-signaling from the co receptor containing CR1/2 to initiate F. tularensis engulfment. In this case, fluidity of the surface cell membrane is a prerequisite for the bacteria's internalization. The results substantially underline the functional heterogeneity of B cell subsets in relation to F. tularensis. PMID- 26161477 TI - Report of the APhA and APhA-ASP Houses of Delegates. PMID- 26161478 TI - Expanding opportunities through patient care: Pharmacists provide care...let me tell you about it. PMID- 26161479 TI - Toward permissionless innovation in health care. PMID- 26161480 TI - Report of the 2015 APhA House of Delegates. PMID- 26161483 TI - Accuracy of community-based blood pressure devices versus validated self-use devices. AB - OBJECTIVES: To examine the accuracy of a community-based blood pressure monitor (CBPM) versus a validated automatic blood pressure monitor (ABPM); to assess providers' recommendations regarding use of CBPMs; and to assess if potentially inaccurate blood pressure readings may result in treatment changes. METHODS: A convenience sample of 50 participants was recruited and met criteria for a randomized, controlled, crossover design trial in a community pharmacy in January and February 2013. Participants completed a screening survey and were educated about how a pharmacist can assist in achieving blood pressure control. Blood pressure measurements were performed using a CBPM and a validated ABPM. Participants were asked to identify their primary care provider (PCP); if identified, the PCP was faxed a survey to complete. The difference in blood pressure readings between the two monitors was examined and PCP survey responses were examined. RESULTS: There were significant differences between the means obtained from the two different monitors for systolic blood pressure (P = 0.006) and diastolic blood pressure (P = 0.012) measurements. Due to differences between readings, recommendations for change in treatment (or initiation of blood pressure medication) may have been different for 38% of participants. PCPs indicated that they often recommend CBPMs for self-monitoring. CONCLUSION: Patients, pharmacists, and providers should be aware of potential inaccuracies when using a CBPM for self-monitoring. PMID- 26161484 TI - Evaluating community pharmacists' HIV testing knowledge: A cross-sectional survey. AB - OBJECTIVES: To assess community pharmacists' knowledge of human immunodeficiency virus (HIV), antiretroviral therapy, and new in-home oral fluid HIV test. METHODS: A cross-sectional questionnaire administered to pharmacists, student pharmacists, and technicians before an education program at the New Mexico Pharmacists Association 2013 Mid-Winter Meeting in Albuquerque, NM. The main outcome measure was community pharmacists' correct response rate of 75% or more. RESULTS: Overall survey response rate of attendees was 89% (173/194 attendees). Among them 87 participants were community pharmacists; 87% of community pharmacists responded correctly when asked how HIV antiretroviral medications work and 84.3% correctly identified known sources of HIV infection. The 75% predefined adequate knowledge threshold was not met on any HIV screening or in home HIV test knowledge items. Only 65.1% of community pharmacists correctly identified the minimum number of antiretroviral drugs that should be included in an ideal HIV treatment regimen. The only variable that positively influenced pharmacists' knowledge was age. An inverse relationship between pharmacist age and HIV knowledge was observed among study participants. CONCLUSION: Community pharmacists from urban and rural areas in New Mexico possessed adequate basic HIV knowledge, but did not demonstrate adequate HIV screening or in-home HIV test knowledge. Future educational interventions aimed at improving pharmacist knowledge in this area are warranted. PMID- 26161485 TI - Pharmacists' perspectives on collaborating with community health workers in diabetes care. AB - OBJECTIVES: To qualitatively assess pharmacists' perspectives on the barriers and facilitators of collaborating with community health workers (CHWs) when caring for patients with diabetes. METHODS: Eight pharmacists were invited to participate in a focus group. All pharmacists had worked with CHWs for 12 months as part of a larger study. Seven pharmacists participated in a single focus group while one pharmacist participated in an individual interview. Data were analyzed by two investigators to identify common themes. RESULTS: Perceived barriers included issues associated with maintaining patient confidentiality, pharmacists' level of comfort with CHWs, uncertainty about CHW roles, and inconsistent communication between pharmacists and CHWs. However, pharmacists reported that the care model fostered improvement in patient-pharmacist communication, patient adherence to medication, and assessment of patients' overall condition. CONCLUSION: Pharmacists expressed positive attitudes and experiences in working with CHWs caring for a minority patient population with poorly controlled diabetes. Most believed that CHWs acted as facilitators and aided them in producing positive clinical outcomes by addressing the multiple psychosocial and contextual dimensions of patient health. Developing approaches for more frequent and effective communication between pharmacists and CHWs was the primary perceived challenge. PMID- 26161486 TI - Disease-specific direct-to-consumer advertising for reminding consumers to take medications. AB - OBJECTIVE: To assess the relationship between disease-specific direct-to-consumer (DTC) advertising, via traditional advertising effectiveness measures, and consumers' self-reported medication-taking behavior. METHODS: Data were gathered for 514 respondents (age 18 and above) using an online survey panel. Participants were exposed to a disease-specific (i.e., nonbranded) DTC advertising for depression. The advertising stimulus created for the study was based on the Food and Drug Administration guidelines for disease-specific DTC advertising and modeled after current print disease-specific DTC advertising. Participants reviewed the advertising stimulus through the online program and then responded to a questionnaire containing closed-ended questions assessing the constructs. Data were analyzed using chi-square tests. All tests were interpreted at an a priori alpha of 0.05. RESULTS: Significantly more respondents who were highly involved, paid more attention to the advertisement, and were responsive to DTC advertisements in the past indicated that the disease-specific DTC advertising stimulus reminded them to take their depression and other medications. CONCLUSION: These exploratory results show disease-specific DTC advertising can help people remember to take their prescription medication when viewed, which may lead to more positive medication-taking behavior and increased medication adherence. Additionally, given the fair balance and legal issues surrounding product-specific DTC advertising, disease-specific DTC advertising can serve as an effective component of the marketing mix for pharmaceutical manufacturers. Future research should attempt to study the impact of disease-specific DTC advertising on consumers' actual medication adherence using standardized adherence measures such as prescription records. PMID- 26161487 TI - Postdischarge community pharmacist-provided home services for patients after hospitalization for heart failure. AB - OBJECTIVE: To establish a community pharmacist-provided home health service to improve medication adherence and reduce 30-day heart failure-related hospital readmissions. SETTING: Visiting Nurse Services of Newport and Bristol Counties located in Portsmouth, RI, from December 2013 to April 2014. PRACTICE DESCRIPTION: Each patient received one in-home visit provided by a Postgraduate Year 1 community pharmacy resident within 1 week of admission to visiting nurse services followed by two follow-up telephone calls, 1 week and 4 weeks after the visit. The in-home visit consisted of a baseline assessment of medication adherence using the Morisky 8-Item Medication Adherence Questionnaire as well as pharmacist-provided education regarding chronic heart failure management. The follow-up telephone calls were used to reassess patient adherence and to monitor for hospital readmission within 30 days of the initial in-home visit. PRACTICE INNOVATION: Community pharmacist-provided in-home medication reconciliation and medication teaching has not been described in the literature previously. In addition, pharmacists are often not included on home health care teams placing patients undergoing transitions in care at risk for potential medication-related errors. MAIN OUTCOME MEASURES: Improvement in medication adherence and reduction in 30-day heart failure-related hospital readmission rates. RESULTS: Ten patients were enrolled from December 2013 through April 2014. Following intervention, all patients saw improvements in adherence questionnaire scores during follow-up. Hospital readmission rates for patients seen by the pharmacist were lower compared with agencywide figures over a similar time period. CONCLUSION: A community pharmacist-provided in-home medication teaching service for patients following recent hospital discharge helps facilitate successful transitions of care from an inpatient to outpatient setting, improves medication adherence and has produced lower observed 30-day heart failure-related hospital readmission rates. Expansion of this or a similar service within the community pharmacy to reach as many patients as possible, including those not using visiting nurse services, could serve to only augment these benefits. PMID- 26161488 TI - Impact of a transition-of-care pharmacist during hospital discharge. AB - OBJECTIVE: To assess the impact of a transition-of-care pharmacist during hospital discharge. SETTING: An academic medical center in southern Arizona. PRACTICE DESCRIPTION: One pharmacist coordinated patient discharges in two inpatient units from August 2012 through July 2013. The pharmacist attended interdisciplinary discharge coordination meetings, ensured appropriate discharge orders, facilitated the filling of medications, and educated patients on discharge medications. PRACTICE INNOVATION: The implementation of a transition-of care pharmacist to provide discharge medication reconciliation and education. MAIN OUTCOME MEASURES: Readmission rates and medication interventions made by the pharmacist at discharge. RESULTS: The pharmacist was involved in the education of 1,011 patients and performed 452 interventions. There were more readmissions per month in the control year versus the year of pharmacist involvement (median 27.5 vs. 25, P = 0.0369). Interventions made by the pharmacist to improve discharge management included starting an omitted medication (23.5%), preventing multiple discharge problems (16.4%), avoiding duplication of therapy (15.7%), correcting insurance issues related to medication coverage (12.2%), changing an improper medication dose or quantity (11.3%), changing an inappropriate prescription for a medication (5.1%), preventing a drug interaction (3.3%), and resolving other problems (12.6%). The most common medication classes involved were antimicrobial agents (9.1%), anticoagulants (8%), antihyperglycemic agents (3.8%), other drug classes (24%), and multiple drug classes (35%). CONCLUSION: A transition-of-care pharmacist is in a unique position to educate patients on hospital discharge, to intercept a substantial number of medication errors, and to resolve insurance issues that may lead to adherence problems. These improvements in care may result in reduced hospital readmission rates. PMID- 26161489 TI - Assessing pharmacist-led annual wellness visits: Interventions made and patient and physician satisfaction. AB - OBJECTIVES: To quantify the nature and frequency of interventions made by pharmacists during a Medicare annual wellness visit (AWV), to determine the association between the number of medications taken and the interventions made, and to assess patient and physician satisfaction with pharmacist-led AWVs. SETTING: Large, teaching, multidisciplinary family medicine practice in North Carolina. PRACTICE DESCRIPTION: Mountain Area Health Education Center (MAHEC) is a large academic practice that serves rural, western North Carolina. There is a heavy emphasis on team-based care. PRACTICE INNOVATION: Pharmacist-led AWV. EVALUATION: Between April 2012 and January 2013, the following were evaluated for 69 patients: the nature and frequency of interventions made, the association between the number of medications taken and the interventions made, and patient and physician satisfaction scores. RESULTS: A total of 247 medication-related interventions and 342 nonmedication interventions were made during the pharmacist led AWVs. The majority of medication interventions (69.6%) involved correcting medication list discrepancies. The number of medications taken was positively associated with the total number of medication interventions (r = 0.37, P <0.01). On a 5-point Likert scale, patients strongly agreed that the AWV is important for their overall health (mean 4.8, median 5) and that they would like to see the same provider next year (mean 4.8, median 5). Physicians strongly disagreed that they would prefer to do the visit themselves (mean 1.5, median 1) and strongly agreed that their patients benefited from a pharmacist-led AWV (mean 5, median 4.9). CONCLUSION: Pharmacists addressed both medication and nonmedication interventions during AWVs. Patients taking a greater number of medications required more medication interventions than patients taking fewer medications. Patients and physicians reported satisfaction with the pharmacist-led AWV. PMID- 26161490 TI - Pediatric seizures and vaccines. PMID- 26161491 TI - Naloxegol oxalate, pirfenidone, and nintedanib. PMID- 26161492 TI - Knowing it and proving it are two different things. PMID- 26161493 TI - Motivational interviewing for medication adherence. AB - OBJECTIVE: To familiarize pharmacists with motivational interviewing as a way to engage patients in discussions about medication adherence. SUMMARY: Motivational interviewing is a collaborative, patient-centered communications skill set that can increase behavior change by stimulating a patient's own internal motivation for change. Pharmacists using motivational interviewing can explore factors associated with medication nonadherence, assess patient ambivalence and/or resistance, and educate a patient to promote medication-adherent behaviors. CONCLUSION: Pharmacists can use motivational interviewing to effectively engage patients in a conversation that addresses medication adherence. PMID- 26161497 TI - Assessment and Application of Density Functional Theory for the Prediction of Structure and Reactivity of Vanadium Complexes. AB - We assess the performance of six density functionals, each paired with one of five basis sets (a total of 30 model chemistries) for the prediction of geometrical parameters in the coordination sphere of nine vanadium complexes (for a total of 270 structural analyses). We find that results are generally consistent over the range of functionals tested and that none fail drastically. For bond lengths, the model chemistry PBE0/QZVP performed the best overall (having a MAD of only 0.02 A from experiment) yet PBE0/6-31G* provides nearly identical results. For bond angles, PBE0 also performed best overall and, when combined with the 6-31G* basis, produces one of the smallest error distributions of any model chemistry tested. We subsequently applied the PBE0/6-31G* model chemistry to understanding the mechanism of action of a [BIMPY]VCl3 catalyst in the polymerization of styrene (Sty) and vinyl acetate (VAc). Our results indicate that the [BIMPY]VCl3 catalyst operates through a unique, two-step reaction pathway: dehalogenation to form a reactive V(II) intermediate (a highly favorable process) followed by a potentially reversible OMRP to control the polymerization of vinyl acetate. Control over vinyl acetate is facilitated by both the higher reactivity of the radical species and the participation of the ester group in the trapping step. In both the Sty and VAc cases we predict relatively poor control of the polymerization with the vanadium catalyst, which is in good agreement with our experimental results. PMID- 26161498 TI - Effects of Industrial Heating Processes of Milk-Based Enteral Formulas on Site Specific Protein Modifications and Their Relationship to in Vitro and in Vivo Protein Digestibility. AB - Heat treatments are applied to milk and dairy products to ensure their microbiological safety and shelf lives. Types of heating processes may have different effects on protein modifications, leading to different protein digestibility. In this study, milk-based liquid nutritional formulas (simulating enteral formulas) were subjected to steam injection ultra-high-temperature treatment or in-can sterilization, and the formulas were investigated by proteomic methods and in vitro and in vivo digestion assays. Proteomic analyses revealed that in-can sterilization resulted in higher signals for N(epsilon) carboxymethyllysine and dephosphorylation of Ser residues in major milk proteins than in steam-injected formula, reflecting the more severe thermal process of in can sterilization. In vitro and in vivo digestion assays indicated that steam injection improved protein digestibility, supposedly by denaturation, while the improvement seemed to be overwhelmed by formation of aggregates that showed resistance to digestion in in-can sterilized formula. Adverse effects of heat treatment on protein digestibility are more likely to be manifested in milk-based formulas than in cow's milk. Although the differences might be of limited significance in terms of amino acid bioavailability, these results emphasize the importance of protein quality of raw materials and selection of heating processes. PMID- 26161499 TI - A Fast Numerical Method for Max-Convolution and the Application to Efficient Max Product Inference in Bayesian Networks. AB - Observations depending on sums of random variables are common throughout many fields; however, no efficient solution is currently known for performing max product inference on these sums of general discrete distributions (max-product inference can be used to obtain maximum a posteriori estimates). The limiting step to max-product inference is the max-convolution problem (sometimes presented in log-transformed form and denoted as "infimal convolution," "min-convolution," or "convolution on the tropical semiring"), for which no O(k log(k)) method is currently known. Presented here is an O(k log(k)) numerical method for estimating the max-convolution of two nonnegative vectors (e.g., two probability mass functions), where k is the length of the larger vector. This numerical max convolution method is then demonstrated by performing fast max-product inference on a convolution tree, a data structure for performing fast inference given information on the sum of n discrete random variables in O(nk log(nk)log(n)) steps (where each random variable has an arbitrary prior distribution on k contiguous possible states). The numerical max-convolution method can be applied to specialized classes of hidden Markov models to reduce the runtime of computing the Viterbi path from nk(2) to nk log(k), and has potential application to the all-pairs shortest paths problem. PMID- 26161502 TI - P-Trifluoromethyl ligands derived from Josiphos in the Ir-catalysed hydrogenation of 3,4-dihydroisoquinoline hydrochlorides. AB - The synthesis of mono P-trifluoromethyl and therefore P-stereogenic Xyliphos derived ligands 5 and their application in the Ir-catalyzed enantioselective hydrogenation of 1-substituted 3,4-dihydroisoquinolinium species (DHIQ) are reported. The ligands were prepared following previous procedures involving the reaction of a bistrifluoromethylphosphine with lithiated (R)-Ugi amine 1. Chloroiridium(i) cyclooctadiene precatalysts containing these new partially electron-poor ligands 9 were found to be poorly active in the hydrogenation of free 1-phenyl-3,4-dihydroisoquinoline 12a. However, the corresponding hydrochloride 12a.HCl was smoothly reduced at 55-60 degrees C and 100 bar hydrogen pressure. The (SP)-configured ligand (SP)-5 yielded significantly higher enantioselectivity in hydrogenation experiments than its P-stereoisomeric counterpart (RP)-5. These new ligands were subsequently applied in the hydrogenation of a series of different 1-substituted 3,4-DHIQ chlorides 12a l.HCl. Good to excellent enantioselectivity was observed for substrates bearing relatively large substituents in position 1, reaching 96% ee for 1-Ph-DHIQ chloride 12a.HCl without the help of any additives. Furthermore, an interesting counter ion effect was found with chloride being the best and hexafluorophosphate being very detrimental to enantioselectivity. PMID- 26161500 TI - A composite double-/single-stranded RNA-binding region in protein Prp3 supports tri-snRNP stability and splicing. AB - Prp3 is an essential U4/U6 di-snRNP-associated protein whose functions and molecular mechanisms in pre-mRNA splicing are presently poorly understood. We show by structural and biochemical analyses that Prp3 contains a bipartite U4/U6 di-snRNA-binding region comprising an expanded ferredoxin-like fold, which recognizes a 3'-overhang of U6 snRNA, and a preceding peptide, which binds U4/U6 stem II. Phylogenetic analyses revealed that the single-stranded RNA-binding domain is exclusively found in Prp3 orthologs, thus qualifying as a spliceosome specific RNA interaction module. The composite double-stranded/single-stranded RNA-binding region assembles cooperatively with Snu13 and Prp31 on U4/U6 di snRNAs and inhibits Brr2-mediated U4/U6 di-snRNA unwinding in vitro. RNP disrupting mutations in Prp3 lead to U4/U6*U5 tri-snRNP assembly and splicing defects in vivo. Our results reveal how Prp3 acts as an important bridge between U4/U6 and U5 in the tri-snRNP and comparison with a Prp24-U6 snRNA recycling complex suggests how Prp3 may be involved in U4/U6 reassembly after splicing. PMID- 26161501 TI - Understanding Dengue Virus Capsid Protein Interaction with Key Biological Targets. AB - Dengue virus (DENV) causes over 500,000 hospitalizations and 20,000 deaths worldwide every year. Dengue epidemics now reach temperate regions due to globalization of trade and travel and climate changes. Currently, there are no successful therapeutic or preventive approaches. We previously developed a peptide drug lead, pep14-23, that inhibits the biologically relevant interaction of DENV capsid (C) protein with lipid droplets (LDs). Surprisingly, pep14-23 also inhibits DENV C interaction with very low-density lipoproteins (VLDL). We thus investigated the similarity between the proposed DENV C molecular targets in LDs and VLDL, respectively, the proteins perilipin 3 (PLIN3) and apolipoprotein E (APOE). APOE N-terminal and PLIN3 C-terminal regions are remarkably similar, namely APOE alpha-helix 4 (APOEalpha4) and PLIN3 alpha-helix 5 (PLIN3alpha5) sequences, which are also highly superimposable structurally. Interestingly, APOE alpha-helical N-terminal sequence and structure superimposes with DENV C alpha helices alpha1 and alpha2. Moreover, the DENV C hydrophobic cleft can accommodate the structurally analogous APOEalpha4 and PLIN3alpha5 helical regions. Mirroring DENV C-LDs interaction (previously shown experimentally to require PLIN3), we experimentally demonstrated that DENV C-VLDL interaction requires APOE. Thus, the results fit well with previous data and suggest future drug development strategies targeting the above mentioned alpha-helical structures. PMID- 26161503 TI - Large-Area Nanoimprinted Colloidal Au Nanocrystal-Based Nanoantennas for Ultrathin Polarizing Plasmonic Metasurfaces. AB - We report a low-cost, large-area fabrication process using solution-based nanoimprinting and compact ligand exchange of colloidal Au nanocrystals to define anisotropic, subwavelength, plasmonic nanoinclusions for optical metasurfaces. Rod-shaped, Au nanocrystal-based nanoantennas possess strong, localized, plasmonic resonances able to control polarization. We fabricate metasurfaces from rod-shaped nanoantennas tailored in size and spacing to demonstrate Au nanocrystal-based quarter-wave plates that operate with extreme bandwidths and provide high polarization conversion efficiencies in the near-to-mid infrared. PMID- 26161504 TI - Activation of Dioxygen by a TAML Activator in Reverse Micelles: Characterization of an Fe(III)Fe(IV) Dimer and Associated Catalytic Chemistry. AB - Iron TAML activators of peroxides are functional catalase-peroxidase mimics. Switching from hydrogen peroxide (H2O2) to dioxygen (O2) as the primary oxidant was achieved by using a system of reverse micelles of Aerosol OT (AOT) in n octane. Hydrophilic TAML activators are localized in the aqueous microreactors of reverse micelles where water is present in much lower abundance than in bulk water. n-Octane serves as a proximate reservoir supplying O2 to result in partial oxidation of Fe(III) to Fe(IV)-containing species, mostly the Fe(III)Fe(IV) (major) and Fe(IV)Fe(IV) (minor) dimers which coexist with the Fe(III) TAML monomeric species. The speciation depends on the pH and the degree of hydration w0, viz., the amount of water in the reverse micelles. The previously unknown Fe(III)Fe(IV) dimer has been characterized by UV-vis, EPR, and Mossbauer spectroscopies. Reactive electron donors such as NADH, pinacyanol chloride, and hydroquinone undergo the TAML-catalyzed oxidation by O2. The oxidation of NADH, studied in most detail, is much faster at the lowest degree of hydration w0 (in "drier micelles") and is accelerated by light through NADH photochemistry. Dyes that are more resistant to oxidation than pinacyanol chloride (Orange II, Safranine O) are not oxidized in the reverse micellar media. Despite the limitation of low reactivity, the new systems highlight an encouraging step in replacing TAML peroxidase-like chemistry with more attractive dioxygen-activation chemistry. PMID- 26161507 TI - Association between Serum Fructosamine and Kidney Function in Nondiabetic Individuals without Chronic Kidney Disease. AB - BACKGROUND: Serum fructosamine (SF) has been considered to be an indicator that estimates glycemic control in patients with diabetes mellitus (DM). There is increasing evidence that SF concentration and oxidative stress are significantly elevated in patients with chronic kidney disease (CKD). However, the data about SF and its association with kidney function are lacking in nondiabetic individuals without CKD. We included 1891 nondiabetic individuals who had not been diagnosed with CKD to determine the association between SF and kidney function. MATERIAL AND METHODS: We conducted a retrospective analysis on the basis of the biochemistry database in nondiabetic individuals without CKD. RESULTS: When eligible participants were stratified in accordance with SF quartiles, from the bottom to the top quartile of SF, a significant decrease of estimated glomerular filtration rate (GFR) was observed in baseline data. SF concentration was negatively associated with estimated GFR (r=-0.066, P=0.004) in the Pearson correlation analysis. Estimated GFR was associated with SF levels independently of glucose (GLU), total cholesterol (TC), triglyceride (TG), and total protein (TP) in multivariable logistic regression analysis (OR=0.984; CI 95% 0.977-0.991; P<0.001). CONCLUSIONS: We suggest that mild elevation of SF concentration is associated with estimated GFR in nondiabetic individuals without CKD. These findings indicate that SF may underlie CKD in nondiabetic individuals. PMID- 26161508 TI - Synthesis of [3]Rotaxanes by the Combination of Copper-Mediated Coupling Reaction and Metal-Template Approach. AB - [3]Rotaxanes with two axle components and one ring component were synthesized by the combination of a coupling reaction using a transition-metal catalyst and a metal-template approach. Thus, [2]rotaxanes were prepared by the oxidative dimerization of alkyne promoted by macrocyclic phenanthroline-CuI complexes. The [2]rotaxane was reacted with a Cu(I) salt and an acyclic ligand to generate a tetrahedral Cu(I) complex. Metal-free [3]rotaxane was isolated by the end-capping reaction of the acyclic ligand, followed by the removal of Cu(I) ion. The stability of the tetrahedral Cu(I) complexes depended on the size of both the ring component and the acyclic ligand, which was correlated with the yield of the corresponding [3]rotaxane. PMID- 26161510 TI - Synthesis Mechanism and Thermal Optimization of an Economical Mesoporous Material Using Silica: Implications for the Effective Removal or Delivery of Ibuprofen. AB - Mesoporous silica materials (MSMs) were synthesized economically using silica (SiO2) as a precursor via a modified alkaline fusion method. The MSM prepared at 500 degrees C (MSM-500) had the highest surface area, pore size, and volume, and the results of isotherms and the kinetics of ibuprofen (IBP) removal indicated that MSM-500 had the highest sorption capacity and fastest removal speed vs. SBA 15 and zeolite. Compared with commercial granular activated carbon (GAC), MSM-500 had a ~100 times higher sorption rate at neutral pH. IBP uptake by MSM-500 was thermodynamically favorable at room temperature, which was interpreted as indicating relatively weak bonding because the entropy (?adsS, -0.07 J mol(-1) K( 1)) was much smaller. Five times recycling tests revealed that MSM-500 had 83-87% recovery efficiencies and slower uptake speeds due to slight deformation of the outer pore structure. In the IBP delivery test, MSM-500 drug loading was 41%, higher than the reported value of SBA-15 (31%). The in vitro release of IBP was faster, almost 100%, reaching equilibrium within a few hours, indicating its effective loading and unloading characteristics. A cost analysis study revealed that the MSM was ~10-70 times cheaper than any other mesoporous silica material for the removal or delivery of IBP. PMID- 26161511 TI - Treatment of hepatitis C-related kidney disease. AB - INTRODUCTION: Hepatitis C virus (HCV) infection has been associated with a large spectrum of glomerular lesions in both native and transplanted kidneys. The most common HCV-associated renal disease is type I membranoproliferative glomerulonephritis usually, but not invariably, in the context of type II mixed cryoglobulinemia (MC). HCV infection is also the major cause of MC, a systemic vasculitis characterized by involvement of small and, less frequently, medium sized vessels. Conflicting data exist on the treatment of HCV-associated glomerular disease. AREAS COVERED: This review examines the drugs used for management of HCV-related kidney disease and discusses current and new strategies. All literature concerning treatment of HCV-associated kidney disease has been retrieved by electronic (Medline) and manual searches. EXPERT OPINION: Various approaches have been recommended for the treatment of HCV-related glomerular disease, including immunosuppressive therapy (corticosteroids, cytotoxic agents and mAbs) and antiviral therapy. These regimens should be considered according to the level or proteinuria and kidney failure. Immunosuppressive agents are recommended in patients with nephrotic syndrome and/or rapidly progressive kidney failure. Antiviral treatment based on IFN and/or ribavirin or triple antiviral therapy (PEGylated-IFN/ribavirin/telaprevir or boceprevir) has been adopted in patients with moderate proteinuria and slow loss of kidney failure; however, the number of patients enrolled was small. Some patients with HCV-related cryoglobulinemic glomerulonephritis have been treated with rituximab but some issues about its role remain to be clarified. The antiviral treatment of HCV-related glomerular disease is expected to improve in the near future with new agents provided with greater efficacy and safety. However, the affordability of these drugs remains a pivotal issue, particularly in low-income countries. PMID- 26161512 TI - Metal-Free Direct Oxidation of Aldehydes to Esters Using TCCA. AB - Aromatic and aliphatic aldehydes are simply converted into esters by an efficient oxidative esterification carried out under mild conditions. The aldehydes are converted in situ into their corresponding acyl chlorides, which are then reacted with primary and secondary aliphatic, benzylic, allylic, and propargylic alcohols and phenols. A variety of esters are obtained in high yields. PMID- 26161514 TI - Aseptic intrafascial and extrafascial abscesses 10 years after a 2-level DIAM insertion procedure. AB - With the aim to prevent the so-called adjacent-segment disease in spinal fusion surgery and to serve as the primary surgical procedure for the management of low back pain syndrome or neurogenic claudication in spinal stenosis, the so-called dynamic spine stabilization is applied using specifically designed implants: interspinous spacers, such as DIAM (Device for Intervertebral Assisted Motion), Coflex, and X-stop. It is commonly accepted that interspinous spacers are made from material that is well tolerated by the body, that their placement is simple, that complications are rare, and that they can greatly benefit the patients. So far, there have not been published studies reporting infective or other complications 10 or more years after the placement of DIAM spacers. The aim of this paper was to present a case of an extremely late complication (after 10 years) in the form of intra- and extrafascial dumbbell abscesses, concomitantly appearing at both levels treated with the DIAM spacer. The paper presents the existence of a significant correlation between CT and MRI findings as well as the deterioration in Oswestry Disability Index and visual analog scale scores. Over time, dynamic spine stabilization might possibly impact reactive accumulation of sterile fluid in the vicinity of an implant and could therefore be related to delayed complications even 10 years after surgery. The finding of a growing layer composed of thick aseptic fluid around the DIAM implant, with a simultaneous occurrence of spinous process osteolysis and formation of a mineralized pseudocyst, bears a considerable risk of delayed inflammatory complications, including abscess, and therefore requires the explantation of the DIAM implant. PMID- 26161513 TI - Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts. AB - Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC) derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle) delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz). Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they identify lack of electrical integration as a challenge to overcome in tissue engineered patches. PMID- 26161515 TI - Biomechanical evaluation of the fixation strength of lumbar pedicle screws using cortical bone trajectory: a finite element study. AB - OBJECT: Cortical bone trajectory (CBT) maximizes thread contact with the cortical bone surface and provides increased fixation strength. Even though the superior stability of axial screw fixation has been demonstrated, little is known about the biomechanical stiffness against multidirectional loading or its characteristics within a unit construct. The purpose of the present study was to quantitatively evaluate the anchorage performance of CBT by the finite element (FE) method. METHODS: Thirty FE models of L-4 vertebrae from human spines (mean age [+/- SD] 60.9 +/- 18.7 years, 14 men and 16 women) were computationally created and pedicle screws were placed using the traditional trajectory (TT) and CBT. The TT screw was 6.5 mm in diameter and 40 mm in length, and the CBT screw was 5.5 mm in diameter and 35 mm in length. To make a valid comparison, the same shape of screw was inserted into the same pedicle in each subject. First, the fixation strength of a single pedicle screw was compared by axial pullout and multidirectional loading tests. Next, vertebral fixation strength within a construct was examined by simulating the motions of flexion, extension, lateral bending, and axial rotation. RESULTS: CBT demonstrated a 26.4% greater mean pullout strength (POS; p = 0.003) than TT, and also showed a mean 27.8% stronger stiffness (p < 0.05) during cephalocaudal loading and 140.2% stronger stiffness (p < 0.001) during mediolateral loading. The CBT construct had superior resistance to flexion and extension loading and inferior resistance to lateral bending and axial rotation. The vertebral fixation strength of the construct was significantly correlated with bone mineral density of the femoral neck and the POS of a single screw. CONCLUSIONS: CBT demonstrated superior fixation strength for each individual screw and sufficient stiffness in flexion and extension within a construct. The TT construct was superior to the CBT construct during lateral bending and axial rotation. PMID- 26161516 TI - Screw fixation technique. PMID- 26161517 TI - Long-term effects of the Cheneau brace on coronal and sagittal alignment in adolescent idiopathic scoliosis. AB - OBJECT: The aim of the present study was to retrospectively evaluate progressive correction of coronal and sagittal alignment and pelvic parameters in patients treated with a Cheneau brace. METHODS: Thirty-two patients with adolescent idiopathic scoliosis (AIS) were assessed before initiation of bracing treatment and at the final follow-up. Each patient underwent radiological examinations, and coronal, sagittal, and pelvic parameters were measured. RESULTS: No statistically significant modification of the Cobb angle was noted. The pelvic incidence remained unchanged in 59% of the cases and increased in 28% of the cases. The sacral slope decreased in 34% of the cases but remained unchanged in 50%. Thoracic kyphosis and lumbar lordosis were significantly decreased, whereas the sagittal vertical axis was significantly increased from a mean of -44.0 to -30.2 mm (p = 0.02). The mean pelvic tilt increased significantly from 4.5 degrees to 8.3 degrees (p = 0.002). CONCLUSIONS: The Cheneau brace can be useful for preventing curvature progression in patients with AIS. However, the results of this study reveal high variability in the effect of brace treatment on sagittal and pelvic alignment. Treatment with the Cheneau brace may also influence sagittal global balance. PMID- 26161518 TI - Differences between Dynamic Cervical Implant and artificial discs. PMID- 26161519 TI - The Brain and Spinal Injury Center score: a novel, simple, and reproducible method for assessing the severity of acute cervical spinal cord injury with axial T2-weighted MRI findings. AB - OBJECT: Previous studies that have evaluated the prognostic value of abnormal changes in signals on T2-weighted MRI scans of an injured spinal cord have focused on the longitudinal extent of this signal abnormality in the sagittal plane. Although the transverse extent of injury and the degree of spared spinal cord white matter have been shown to be important for predicting outcomes in preclinical animal models of spinal cord injury (SCI), surprisingly little is known about the prognostic value of altered T2 relaxivity in humans in the axial plane. METHODS: The authors undertook a retrospective chart review of 60 patients who met the inclusion criteria of this study and presented to the authors' Level I trauma center with an acute blunt traumatic cervical SCI. Within 48 hours of admission, all patients underwent MRI examination, which included axial and sagittal T2 images. Neurological symptoms, evaluated with the grades according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS), at the time of admission and at hospital discharge were correlated with MRI findings. Five distinct patterns of intramedullary spinal cord T2 signal abnormality were defined in the axial plane at the injury epicenter. These patterns were assigned ordinal values ranging from 0 to 4, referred to as the Brain and Spinal Injury Center (BASIC) scores, which encompassed the spectrum of SCI severity. RESULTS: The BASIC score strongly correlated with neurological symptoms at the time of both hospital admission and discharge. It also distinguished patients initially presenting with complete injury who improved by at least one AIS grade by the time of discharge from those whose injury did not improve. The authors' proposed score was rapid to apply and showed excellent interrater reliability. CONCLUSIONS: The authors describe a novel 5-point ordinal MRI score for classifying acute SCIs on the basis of axial T2-weighted imaging. The proposed BASIC score stratifies the SCIs according to the extent of transverse T2 signal abnormality during the acute phase of the injury. The new score improves on current MRI-based prognostic descriptions for SCI by reflecting functionally and anatomically significant patterns of intramedullary T2 signal abnormality in the axial plane. PMID- 26161520 TI - Early outcome and predictors of early outcome in patients treated surgically for central cord syndrome. AB - OBJECT: The purpose of this study was to characterize changes in American Spinal Injury Association motor score (AMS) in the 1st week after traumatic central cord syndrome (CCS) to identify predictors of improved early outcome in patients treated with early versus delayed surgical intervention. METHODS: All patients presenting to a regional spinal cord injury center between January 2004 and June 2009 were queried for those with a diagnosis of CCS. Patients treated conservatively were excluded. A prospectively maintained spinal cord injury database was used to track AMS throughout each patient's hospitalization. Hospital records provided information regarding demographics, presenting neurological examination, imaging findings, comorbidities, timing and nature of surgical procedures, and length of stay (LOS) in the hospital and intensive care unit (ICU). Patients were separated into those who underwent early surgery, within 1 day of presentation (early group), and those who underwent surgery on a delayed basis (delayed group). Differences between groups were analyzed using the Student t-test and chi-square test. Predictors of outcome were identified using correlation analysis and multiple linear regression. RESULTS: Of 426 patients in the database, 80 (18.8%) were diagnosed as having CCS, and 68 of them ultimately underwent surgical decompression. Nineteen (28%) of 68 patients underwent surgery within 1 day of presentation (early group) while the remaining 49 patients (72%) underwent surgery on a delayed basis (delayed group). The mean age in the early group was significantly younger than that of the delayed group (52 vs 59 years, p = 0.049). Other characteristics were similar between groups including sex, proportion of patients with cord edema on MRI (44% early vs 55% delayed, p = 0.47), and proportion of patients with cervical fracture (26% early vs 28% delayed, p = 0.98). Patients in the early group presented with an AMS of 62.5 versus 70.0 for the delayed group (p = 0.36). No difference in the change in AMS was seen at 7 days between the early group (-2.9 points) and the delayed group ( 4.2 points) (p = 0.34). Additionally, the number of patients who had early improvement was similar between the early and delayed groups (50% vs. 48%, respectively, p = 0.94). Neither time in the ICU (3.4 vs. 3.4 days, p = 0.84) nor the overall LOS (10.5 vs 12.5 days, p = 0.59) was different in the early versus delayed groups, respectively. Correlation analysis and multiple linear regression demonstrated early surgery was not associated with change in AMS or AMS at Day 7. Age was identified as the only significant predictor of change in AMS and had a negative effect (coefficient = -0.34, p = 0.025). CONCLUSIONS: Early treatment of patients with CCS remains controversial. Although some long-term neurological recovery is expected in patients with a CCS, surgeons and patients should not expect early neurological improvement with or without early operative intervention. PMID- 26161521 TI - An Effective Approach for NRSFM of Small-Size Image Sequences. AB - In recent years, non-rigid structure from motion (NRSFM) has become one of the hottest issues in computer vision due to its wide applications. In practice, the number of available high-quality images may be limited in many cases. Under such a condition, the performances may not be satisfactory when existing NRSFM algorithms are applied directly to estimate the 3D coordinates of a small-size image sequence. In this paper, a sub-sequence-based integrated algorithm is proposed to deal with the NRSFM problem with small sequence sizes. In the proposed method, sub-sequences are first extracted from the original sequence. In order to obtain diversified estimations, multiple weaker estimators are constructed by applying the extracted sub-sequences to a recent NRSFM algorithm with a rotation-invariant kernel (RIK). Compared to other first-order statistics, the trimmed mean is a relatively robust statistic. Considering the fact that the estimations of some weaker estimators may have large errors, the trimmed means of the outputs for all the weaker estimators are computed to determine the final estimated 3D shapes. Compared to some existing methods, the proposed algorithm can achieve a higher estimation accuracy, and has better robustness. Experimental results on several widely used image sequences demonstrate the effectiveness and feasibility of the proposed algorithm. PMID- 26161522 TI - Hearing Loss: Foreword. PMID- 26161523 TI - Hearing Loss: Diagnosis and Evaluation. AB - Hearing loss is a common disability in the United States, most frequent among men, elderly individuals, and veterans but is increasingly affecting other younger adults. Types of hearing loss include sensorineural, conductive, and mixed. Hearing loss in children often is related to infections, time spent in a neonatal intensive care unit, and genetic etiologies. Presbycusis (ie, age related hearing loss) is the most common etiology in adults. Adverse effects of untreated hearing loss include isolation, depression, lower income, and higher unemployment. Hearing aid use reduces levels of disability, cognitive impairment, and psychosocial distress while improving quality of life. At least 75% of individuals with hearing loss are not receiving treatment for it. All infants should be screened for hearing loss, as should children and adults with risk factors. The Joint Commission on Infant Hearing Screening has a 1-3-6 goal for screening: identification by age 1 month, confirmation by age 3 months, and intervention by age 6 months. The presence of an ongoing physician-patient relationship increases the likelihood that a patient will admit to having a hearing loss. Adults can be screened using single-question or standardized instrument screens. All patients with suspected hearing loss should undergo audiometry by an audiology subspecialist. PMID- 26161524 TI - Hearing Loss: Hearing Augmentation. AB - Etiologies of hearing loss vary. When hearing loss is diagnosed, referral to an otology subspecialist, audiology subspecialist, or hearing aid dispenser to discuss treatment options is appropriate. Conventional hearing aids provide increased sound pressure in the ear canal for detection of sounds that might otherwise be soft or inaudible. Hearing aids can be used for sensorineural, conductive, or mixed hearing loss by patients with a wide range of hearing loss severity. The most common type of hearing loss is high-frequency, which affects audibility and perception of speech consonants, but not vowels. As the severity of hearing loss increases, the benefit of hearing aids for speech perception decreases. Implantable devices such as cochlear implants, middle ear implants, and bone-anchored implants can benefit specific patient groups. Hearing assistive technology devices provide auditory, visual, or tactile information to augment hearing and increase environmental awareness of sounds. Hearing assistive devices include wireless assistive listening device systems, closed captioning, hearing aid-compatible telephones, and other devices. For some patients, financial barriers and health insurance issues limit acquisition of hearing aids, implantable devices, and hearing assistive devices. Physicians should be aware that for some patients and families, hearing augmentation may not be desired for cultural reasons. PMID- 26161525 TI - Hearing Loss: Communicating With the Patient Who Is Deaf or Hard of Hearing. AB - Hearing loss impairs health care communication and adversely affects patient satisfaction, treatment adherence, and use of health services. Hearing loss is the third most common chronic health condition among older patients after hypertension and arthritis, but only 15% to 18% of older adults are screened for hearing loss during health maintenance examinations. Patients with hearing loss may be reluctant to disclose it because of fear of ageism, perceptions of disability, and vanity. Lipreading and note writing often are ineffective ways to communicate with deaf and hard of hearing (DHH) patients who use American Sign Language; use of medical sign language interpreters is preferred. A variety of strategies can improve the quality of health care communication for DHH patients, such as the physician facing the patient, listening attentively, and using visual tools. Physicians should learn what hearing loss means to the DHH patient. Deaf American Sign Language users may not perceive hearing loss as a disability but as a cultural identity. Patients' preferred communication strategies will vary. Relay services, electronic communication, and other telecommunications methods can be helpful, but family physicians and medical staff should learn from each DHH patient about which communication strategies will work best. PMID- 26161526 TI - Hearing Loss: Issues in the Deaf and Hard of Hearing Communities. AB - Hearing loss can lead to impairments in language and speech acquisition, educational attainment, social development, and reading achievement. More than 90% of deaf and hard of hearing (DHH) children are born to hearing parents who may lack the knowledge or experience to effectively care for a child with hearing loss. Family involvement is crucial for teaching self-advocacy and global communication skills, optimizing social development, and helping DHH individuals understand and manage external attitudes about deafness and hearing loss. American Sign Language is a naturally developed language with an always-expanding lexicon and grammatical structures different from those of English. Teaching spoken English and American Sign Language equally, often called bilingual bimodal education, can enhance academic and reading achievement as well as language and psychosocial development. Formal schooling options for a DHH child include enrollment in a public or private school system (often called inclusion, integration, or mainstreaming), a school for the deaf, or a bilingual school. Individuals with hearing loss experience stereotypes and biases that create disparities in health insurance coverage, health care access, and outcomes of mental and physical conditions. Family physicians should recognize and minimize biases to improve health care in the DHH community. PMID- 26161527 TI - Luminescent Rhenium(I) and Iridium(III) Polypyridine Complexes as Biological Probes, Imaging Reagents, and Photocytotoxic Agents. AB - Although the interactions of transition metal complexes with biological molecules have been extensively studied, the use of luminescent transition metal complexes as intracellular sensors and bioimaging reagents has not been a focus of research until recently. The main advantages of luminescent transition metal complexes are their high photostability, long-lived phosphorescence that allows time-resolved detection, and large Stokes shifts that can minimize the possible self-quenching effect. Also, by the use of transition metal complexes, the degree of cellular uptake can be readily determined using inductively coupled plasma mass spectrometry. For more than a decade, we have been interested in the development of luminescent transition metal complexes as covalent labels and noncovalent probes for biological molecules. We argue that many transition metal polypyridine complexes display triplet charge transfer ((3)CT) emission that is highly sensitive to the local environment of the complexes. Hence, the biological labeling and binding interactions can be readily reflected by changes in the photophysical properties of the complexes. In this laboratory, we have modified luminescent tricarbonylrhenium(I) and bis-cyclometalated iridium(III) polypyridine complexes of general formula [Re(bpy-R(1))(CO)3(py-R(2))](+) and [Ir(ppy-R(3))2(bpy-R(4))](+), respectively, with reactive functional groups and used them to label the amine and sulfhydryl groups of biomolecules such as oligonucleotides, amino acids, peptides, and proteins. Additionally, using a range of biological substrates such as biotin, estradiol, and indole, we have designed luminescent rhenium(I) and iridium(III) polypyridine complexes as noncovalent probes for biological receptors. The interesting results generated from these studies have prompted us to investigate the possible applications of luminescent transition metal complexes in intracellular systems. Thus, in the past few years, we have developed an interest in the cytotoxic activity, cellular uptake, and bioimaging applications of these complexes. Additionally, we and other research groups have demonstrated that many transition metal complexes have facile cellular uptake and organelle-localization properties and that their cytotoxic activity can be readily controlled. For example, complexes that can target the nucleus, nucleolus, mitochondria, lysosomes, endoplasmic reticulum, and Golgi apparatus have been identified. We anticipate that this selective localization property can be utilized in the development of intracellular sensors and bioimaging reagents. Thus, we have functionalized luminescent rhenium(I) and iridium(III) polypyridine complexes with various pendants, including molecule binding moieties, sugar molecules, bioorthogonal functional groups, and polymeric chains such as poly(ethylene glycol) and polyethylenimine, and examined their potentials as biological reagents. This Account describes our design of luminescent rhenium(I) and iridium(III) polypyridine complexes and explains how they can serve as a new generation of biological reagents for diagnostic and therapeutic applications. PMID- 26161528 TI - AAA-ATPase FIDGETIN-LIKE 1 and Helicase FANCM Antagonize Meiotic Crossovers by Distinct Mechanisms. AB - Meiotic crossovers (COs) generate genetic diversity and are critical for the correct completion of meiosis in most species. Their occurrence is tightly constrained but the mechanisms underlying this limitation remain poorly understood. Here we identified the conserved AAA-ATPase FIDGETIN-LIKE-1 (FIGL1) as a negative regulator of meiotic CO formation. We show that Arabidopsis FIGL1 limits CO formation genome-wide, that FIGL1 controls dynamics of the two conserved recombinases DMC1 and RAD51 and that FIGL1 hinders the interaction between homologous chromosomes, suggesting that FIGL1 counteracts DMC1/RAD51 mediated inter-homologue strand invasion to limit CO formation. Further, depleting both FIGL1 and the previously identified anti-CO helicase FANCM synergistically increases crossover frequency. Additionally, we showed that the effect of mutating FANCM on recombination is much lower in F1 hybrids contrasting from the phenotype of inbred lines, while figl1 mutation equally increases crossovers in both contexts. This shows that the modes of action of FIGL1 and FANCM are differently affected by genomic contexts. We propose that FIGL1 and FANCM represent two successive barriers to CO formation, one limiting strand invasion, the other disassembling D-loops to promote SDSA, which when both lifted, leads to a large increase of crossovers, without impairing meiotic progression. PMID- 26161529 TI - Phosphodiesterase-4D Knock-down in the Prefrontal Cortex Alleviates Chronic Unpredictable Stress-Induced Depressive-Like Behaviors and Memory Deficits in Mice. AB - Phosphodiesterase 4 (PDE4) has four isoforms (PDE4A-D) with at least 25 splice variants. PDE4 subtype nonselective inhibitors produce potent antidepressant-like and cognition-enhancing effects via increased intracellular cyclic AMP (cAMP) signaling in the brain. Our previous data have demonstrated that long-form PDE4Ds appear to be involved in these pharmacological properties of PDE4 inhibitors in the normal animals. However, it is not clear whether long-form PDE4Ds are critical for the behaviors and related cellular signaling/neuronal plasticity/neuroendocrine alterations in the depressed animals. In the present study, animals exposed to the chronic unpredictable stress (CUS), a rodent model of depression, exhibited elevated corticosterone, depressive-like behavior, memory deficits, accompanied with decreased cAMP-PKA-CREB and cAMP-ERK1/2-CREB signaling and neuroplasticity. These alterations induced by CUS were reversed by RNA interference (RNAi)-mediated prefrontal cortex long-form PDE4Ds (especially PDE4D4 and PDE4D5) knock-down, similar to the effects of the PDE4 subtype nonselective inhibitor rolipram. Furthermore, these effects of RNAi were not enhanced by rolipram. These data indicate a predominant role of long-form PDE4Ds in the pharmacotherapies of PDE4 inhibitors for depression and concomitant memory deficits. Long-form PDE4Ds, especially PDE4D4 and PDE4D5, appear to be the promising targets for the development of antidepressants with high therapeutic indices. PMID- 26161531 TI - Chemotactic Motility of Pseudomonas fluorescens F113 under Aerobic and Denitrification Conditions. AB - The sequence of the genome of Pseudomonas fluorescens F113 has shown the presence of multiple traits relevant for rhizosphere colonization and plant growth promotion. Among these traits are denitrification and chemotactic motility. Besides aerobic growth, F113 is able to grow anaerobically using nitrate and nitrite as final electron acceptors. F113 is able to perform swimming motility under aerobic conditions and under anaerobic conditions when nitrate is used as the electron acceptor. However, nitrite can not support swimming motility. Regulation of swimming motility is similar under aerobic and anaerobic conditions, since mutants that are hypermotile under aerobic conditions, such as gacS, sadB, kinB, algU and wspR, are also hypermotile under anaerobic conditions. However, chemotactic behavior is different under aerobic and denitrification conditions. Unlike most pseudomonads, the F113 genome encode three complete chemotaxis systems, Che1, Che2 and Che3. Mutations in each of the cheA genes of the three Che systems has shown that the three systems are functional and independent. Mutation of the cheA1 gene completely abolished swimming motility both under aerobic and denitrification conditions. Mutation of the cheA2 gene, showed only a decrease in swimming motility under both conditions, indicating that this system is not essential for chemotactic motility but is necessary for optimal motility. Mutation of the cheA3 gene abolished motility under denitrification conditions but only produced a decrease in motility under aerobic conditions. The three Che systems proved to be implicated in competitive rhizosphere colonization, being the cheA1 mutant the most affected. PMID- 26161530 TI - Against All Odds: Trehalose-6-Phosphate Synthase and Trehalase Genes in the Bdelloid Rotifer Adineta vaga Were Acquired by Horizontal Gene Transfer and Are Upregulated during Desiccation. AB - The disaccharide sugar trehalose is essential for desiccation resistance in most metazoans that survive dryness; however, neither trehalose nor the enzymes involved in its metabolism have ever been detected in bdelloid rotifers despite their extreme resistance to desiccation. Here we screened the genome of the bdelloid rotifer Adineta vaga for genes involved in trehalose metabolism. We discovered a total of four putative trehalose-6-phosphate synthase (TPS) and seven putative trehalase (TRE) gene copies in the genome of this ameiotic organism; however, no trehalose-6-phosphate phosphatase (TPP) gene or domain was detected. The four TPS copies of A. vaga appear more closely related to plant and fungi proteins, as well as to some protists, whereas the seven TRE copies fall in bacterial clades. Therefore, A. vaga likely acquired its trehalose biosynthesis and hydrolysis genes by horizontal gene transfers. Nearly all residues important for substrate binding in the predicted TPS domains are highly conserved, supporting the hypothesis that several copies of the genes might be functional. Besides, RNAseq library screening showed that trehalase genes were highly expressed compared to TPS genes, explaining probably why trehalose had not been detected in previous studies of bdelloids. A strong overexpression of their TPS genes was observed when bdelloids enter desiccation, suggesting a possible signaling role of trehalose-6-phosphate or trehalose in this process. PMID- 26161533 TI - The Nazeris Fauna of the Luoxiao Mountain Range, China. (Coleoptera, Staphylinidae, Paederinae). AB - Fourteen species of Nazeris Fauvel are recorded from the Luoxiao Mountains. Twelve of them are described as new: N. luoxiaoshanus, N. pengzhongi, N. divisus, N. paradivisus, N. xiaobini, N. congchaoi, N. nannani, N. rufus, N. ziweii, N. daweishanus, N. prominens, and N. zekani. N. inaequalis Assing, 2014 is newly recorded from Hunan Province. PMID- 26161532 TI - Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein. AB - Prevention efforts for respiratory syncytial virus (RSV) have been advanced due to the recent isolation and characterization of antibodies that specifically recognize the prefusion conformation of the RSV fusion (F) glycoprotein. These potently neutralizing antibodies are in clinical development for passive prophylaxis and have also aided the design of vaccine antigens that display prefusion-specific epitopes. To date, prefusion-specific antibodies have been shown to target two antigenic sites on RSV F, but both of these sites are also present on monomeric forms of F. Here we present a structural and functional characterization of human antibody AM14, which potently neutralized laboratory strains and clinical isolates of RSV from both A and B subtypes. The crystal structure and location of escape mutations revealed that AM14 recognizes a quaternary epitope that spans two protomers and includes a region that undergoes extensive conformational changes in the pre- to postfusion F transition. Binding assays demonstrated that AM14 is unique in its specific recognition of trimeric furin-cleaved prefusion F, which is the mature form of F on infectious virions. These results demonstrate that the prefusion F trimer contains potent neutralizing epitopes not present on monomers and that AM14 should be particularly useful for characterizing the conformational state of RSV F-based vaccine antigens. PMID- 26161534 TI - PINK1-Parkin-Mediated Mitophagy Protects Mitochondrial Integrity and Prevents Metabolic Stress-Induced Endothelial Injury. AB - Mitochondrial injury and dysfunction, a significant feature in metabolic syndrome, triggers endothelial cell dysfunction and cell death. Increasing evidence suggests that mitophagy, a process of autophagic turnover of damaged mitochondria, maintains mitochondrial integrity. PINK1 (phosphatase and tensin homolog (PTEN)-induced putative kinase 1) and Parkin signaling is a key pathway in mitophagy control. In this study, we examined whether this pathway could protect mitochondria under metabolic stress. We found that palmitic acid (PA) induced significant mitophagy and activated PINK1 and Parkin in endothelial cells. Knocking down PINK1 or Parkin reduced mitophagy, leading to impaired clearance of damaged mitochondria and intracellular accumulation of mitochondrial fragments. Furthermore, PINK1 and Parkin prevented PA-induced mitochondrial dysfunction, ROS production and apoptosis. Finally, we show that PINK1 and Parkin were up-regulated in vascular wall of obese mice and diabetic mice. Our study demonstrates that PINK1-Parkin pathway is activated in response to metabolic stress. Through induction of mitophagy, this pathway protects mitochondrial integrity and prevents metabolic stress-induced endothelial injury. PMID- 26161535 TI - New Algorithm for Managing Childhood Illness Using Mobile Technology (ALMANACH): A Controlled Non-Inferiority Study on Clinical Outcome and Antibiotic Use in Tanzania. AB - INTRODUCTION: The decline of malaria and scale-up of rapid diagnostic tests calls for a revision of IMCI. A new algorithm (ALMANACH) running on mobile technology was developed based on the latest evidence. The objective was to ensure that ALMANACH was safe, while keeping a low rate of antibiotic prescription. METHODS: Consecutive children aged 2-59 months with acute illness were managed using ALMANACH (2 intervention facilities), or standard practice (2 control facilities) in Tanzania. Primary outcomes were proportion of children cured at day 7 and who received antibiotics on day 0. RESULTS: 130/842 (15?4%) in ALMANACH and 241/623 (38?7%) in control arm were diagnosed with an infection in need for antibiotic, while 3?8% and 9?6% had malaria. 815/838 (97?3%;96?1-98.4%) were cured at D7 using ALMANACH versus 573/623 (92?0%;89?8-94?1%) using standard practice (p<0?001). Of 23 children not cured at D7 using ALMANACH, 44% had skin problems, 30% pneumonia, 26% upper respiratory infection and 13% likely viral infection at D0. Secondary hospitalization occurred for one child using ALMANACH and one who eventually died using standard practice. At D0, antibiotics were prescribed to 15?4% (12?9-17?9%) using ALMANACH versus 84?3% (81?4-87?1%) using standard practice (p<0?001). 2?3% (1?3-3.3) versus 3?2% (1?8-4?6%) received an antibiotic secondarily. CONCLUSION: Management of children using ALMANACH improve clinical outcome and reduce antibiotic prescription by 80%. This was achieved through more accurate diagnoses and hence better identification of children in need of antibiotic treatment or not. The building on mobile technology allows easy access and rapid update of the decision chart. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201011000262218. PMID- 26161537 TI - Confidence in Phase Definition for Periodicity in Genes Expression Time Series. AB - Circadian oscillation in baseline gene expression plays an important role in the regulation of multiple cellular processes. Most of the knowledge of circadian gene expression is based on studies measuring gene expression over time. Our ability to dissect molecular events in time is determined by the sampling frequency of such experiments. However, the real peaks of gene activity can be at any time on or between the time points at which samples are collected. Thus, some genes with a peak activity near the observation point have their phase of oscillation detected with better precision then those which peak between observation time points. Separating genes for which we can confidently identify peak activity from ambiguous genes can improve the analysis of time series gene expression. In this study we propose a new statistical method to quantify the phase confidence of circadian genes. The numerical performance of the proposed method has been tested using three real gene expression data sets. PMID- 26161536 TI - Development of Cortical Morphology Evaluated with Longitudinal MR Brain Images of Preterm Infants. AB - INTRODUCTION: The cerebral cortex develops rapidly in the last trimester of pregnancy. In preterm infants, brain development is very vulnerable because of their often complicated extra-uterine conditions. The aim of this study was to quantitatively describe cortical development in a cohort of 85 preterm infants with and without brain injury imaged at 30 and 40 weeks postmenstrual age (PMA). METHODS: In the acquired T2-weighted MR images, unmyelinated white matter (UWM), cortical grey matter (CoGM), and cerebrospinal fluid in the extracerebral space (CSF) were automatically segmented. Based on these segmentations, cortical descriptors evaluating volume, surface area, thickness, gyrification index, and global mean curvature were computed at both time points, for the whole brain, as well as for the frontal, temporal, parietal, and occipital lobes separately. Additionally, visual scoring of brain abnormality was performed using a conventional scoring system at 40 weeks PMA. RESULTS: The evaluated descriptors showed larger change in the occipital lobes than in the other lobes. Moreover, the cortical descriptors showed an association with the abnormality scores: gyrification index and global mean curvature decreased, whereas, interestingly, median cortical thickness increased with increasing abnormality score. This was more pronounced at 40 weeks PMA than at 30 weeks PMA, suggesting that the period between 30 and 40 weeks PMA might provide a window of opportunity for intervention to prevent delay in cortical development. PMID- 26161538 TI - Tacrolimus Protects Podocytes from Injury in Lupus Nephritis Partly by Stabilizing the Cytoskeleton and Inhibiting Podocyte Apoptosis. AB - OBJECTIVE: Several studies have reported that tacrolimus (TAC) significantly reduced proteinuria in lupus nephritis (LN) patients and mouse models. However, the mechanism for this effect remains undetermined. This study explored the mechanism of how TAC protects podocytes from injury to identify new targets for protecting renal function. METHODS: MRL/lpr mice were given TAC at a dosage of 0.1 mg/kg per day by intragastric administration for 8 weeks. Urine and blood samples were collected. Kidney sections (2 MUm) were stained with hematoxylin eosin (HE), periodic acid-Schiff base (PAS) and Masson's trichrome stain. Mouse podocyte cells (MPC5) were treated with TAC and/or TGF-beta1 for 48 h. The mRNA levels and protein expression of synaptopodin and Wilms' tumor 1 (WT1) were determined by real-time PCR, Western blotting and/or immunofluorescence, respectively. Flow cytometry was used to detect cell apoptosis with annexin V. Podocyte foot processes were observed under transmission electron microscopy. IgG and C3 deposition were assessed with immunofluorescence assays and confocal microscopy. RESULTS: Synaptopodin expression significantly decreased in MRL/lpr disease control mice, accompanied by increases in 24-h proteinuria, blood urea nitrogen, and serum creatinine. TAC, however, reduced proteinuria, improved renal function, attenuated renal pathology, restored synaptopodin expression and preserved podocyte numbers. In MPC5 cells, TGF-beta1 enhanced F-actin damage in podocytes and TAC stabilized it. TAC also decreased TGF-beta1-induced podocyte apoptosis in vitro and inhibited foot process fusion in MRL/lpr mice. In addition, our results also showed TAC inhibited glomerular deposition of IgG and C3. CONCLUSION: This study demonstrated that TAC reduced proteinuria and preserved renal function in LN through protecting podocytes from injury partly by stabilizing podocyte actin cytoskeleton and inhibiting podocyte apoptosis. PMID- 26161539 TI - Salix purpurea Stimulates the Expression of Specific Bacterial Xenobiotic Degradation Genes in a Soil Contaminated with Hydrocarbons. AB - The objectives of this study were to uncover Salix purpurea-microbe xenobiotic degradation systems that could be harnessed in rhizoremediation, and to identify microorganisms that are likely involved in these partnerships. To do so, we tested S. purpurea's ability to stimulate the expression of 10 marker microbial oxygenase genes in a soil contaminated with hydrocarbons. In what appeared to be a detoxification rhizosphere effect, transcripts encoding for alkane 1 monooxygenases, cytochrome P450 monooxygenases, laccase/polyphenol oxidases, and biphenyl 2,3-dioxygenase small subunits were significantly more abundant in the vicinity of the plant's roots than in bulk soil. This gene expression induction is consistent with willows' known rhizoremediation capabilities, and suggests the existence of S. purpurea-microbe systems that target many organic contaminants of interest (i.e. C4-C16 alkanes, fluoranthene, anthracene, benzo(a)pyrene, biphenyl, polychlorinated biphenyls). An enhanced expression of the 4 genes was also observed within the bacterial orders Actinomycetales, Rhodospirillales, Burkholderiales, Alteromonadales, Solirubrobacterales, Caulobacterales, and Rhizobiales, which suggest that members of these taxa are active participants in the exposed partnerships. Although the expression of the other 6 marker genes did not appear to be stimulated by the plant at the community level, signs of additional systems that rest on their expression by members of the orders Solirubrobacterales, Sphingomonadales, Actinomycetales, and Sphingobacteriales were observed. Our study presents the first transcriptomics-based identification of microbes whose xenobiotic degradation activity in soil appears stimulated by a plant. It paints a portrait that contrasts with the current views on these consortia's composition, and opens the door for the development of laboratory test models geared towards the identification of root exudate characteristics that limit the efficiency of current willow-based rhizoremediation applications. PMID- 26161540 TI - On Intensive Late Holocene Iron Mining and Production in the Northern Congo Basin and the Environmental Consequences Associated with Metallurgy in Central Africa. AB - An ongoing question in paleoenvironmental reconstructions of the central African rainforest concerns the role that prehistoric metallurgy played in shaping forest vegetation. Here we report evidence of intensive iron-ore mining and smelting in forested regions of the northern Congo Basin dating to the late Holocene. Volumetric estimates on extracted iron-ore and associated slag mounds from prehistoric sites in the southern Central African Republic suggest large-scale iron production on par with other archaeological and historically-known iron fabrication areas. These data document the first evidence of intensive iron mining and production spanning approximately 90 years prior to colonial occupation (circa AD 1889) and during an interval of time that is poorly represented in the archaeological record. Additional site areas pre-dating these remains by 3-4 centuries reflect an earlier period of iron production on a smaller scale. Microbotanical evidence from a sediment core collected from an adjacent riparian trap shows a reduction in shade-demanding trees in concert with an increase in light-demanding species spanning the time interval associated with iron intensification. This shift occurs during the same time interval when many portions of the Central African witnessed forest transgressions associated with a return to moister and more humid conditions beginning 500-100 years ago. Although data presented here do not demonstrate that iron smelting activities caused widespread vegetation change in Central Africa, we argue that intense mining and smelting can have localized and potentially regional impacts on vegetation communities. These data further demonstrate the high value of pairing archeological and paleoenvironmental analyses to reconstruct regional-scale forest histories. PMID- 26161542 TI - Living on the edge: transfer and traffic of E. coli in a confined flow. AB - We quantitatively study the transport of E. coli near the walls of confined microfluidic channels, and in more detail along the edges formed by the interception of two perpendicular walls. Our experiments establish the connection between bacterial motion at the flat surface and at the edges and demonstrate the robustness of the upstream motion at the edges. Upstream migration of E. coli at the edges is possible at much larger flow rates compared to motion at the flat surfaces. Interestingly, the speed of bacteria at the edges mainly results from collisions between bacteria moving along this single line. We show that upstream motion not only takes place at the edge but also in an "edge boundary layer" whose size varies with the applied flow rate. We quantify the bacterial fluxes along the bottom walls and the edges and show that they result from both the transport velocity of bacteria and the decrease of surface concentration with increasing flow rate due to erosion processes. We rationalize our findings as a function of local variations in the shear rate in the rectangular channels and hydrodynamic attractive forces between bacteria and walls. PMID- 26161541 TI - A Targeting Microbubble for Ultrasound Molecular Imaging. AB - RATIONALE: Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. OBJECTIVE: To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. METHODS AND RESULTS: Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab')2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|>=0.8), demonstrating a high degree of non-invasive molecular quantification. CONCLUSIONS: Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)-(iii) desired for clinical applications. PMID- 26161543 TI - Site-Dependent Degradation of a Non-Cleavable Auristatin-Based Linker-Payload in Rodent Plasma and Its Effect on ADC Efficacy. AB - The efficacy of an antibody-drug conjugate (ADC) is dependent on the properties of its linker-payload which must remain stable while in systemic circulation but undergo efficient processing upon internalization into target cells. Here, we examine the stability of a non-cleavable Amino-PEG6-based linker bearing the monomethyl auristatin D (MMAD) payload site-specifically conjugated at multiple positions on an antibody. Enzymatic conjugation with transglutaminase allows us to create a stable amide linkage that remains intact across all tested conjugation sites on the antibody, and provides us with an opportunity to examine the stability of the auristatin payload itself. We report a position-dependent degradation of the C terminus of MMAD in rodent plasma that has a detrimental effect on its potency. The MMAD cleavage can be eliminated by either modifying the C terminus of the toxin, or by selection of conjugation site. Both approaches result in improved stability and potency in vitro and in vivo. Furthermore, we show that the MMAD metabolism in mouse plasma is likely mediated by a serine based hydrolase, appears much less pronounced in rat, and was not detected in cynomolgus monkey or human plasma. Clarifying these species differences and controlling toxin degradation to optimize ADC stability in rodents is essential to make the best ADC selection from preclinical models. The data presented here demonstrate that site selection and toxin susceptibility to mouse plasma degradation are important considerations in the design of non-cleavable ADCs, and further highlight the benefits of site-specific conjugation methods. PMID- 26161544 TI - Accelerated Sensitivity Analysis in High-Dimensional Stochastic Reaction Networks. AB - Existing sensitivity analysis approaches are not able to handle efficiently stochastic reaction networks with a large number of parameters and species, which are typical in the modeling and simulation of complex biochemical phenomena. In this paper, a two-step strategy for parametric sensitivity analysis for such systems is proposed, exploiting advantages and synergies between two recently proposed sensitivity analysis methodologies for stochastic dynamics. The first method performs sensitivity analysis of the stochastic dynamics by means of the Fisher Information Matrix on the underlying distribution of the trajectories; the second method is a reduced-variance, finite-difference, gradient-type sensitivity approach relying on stochastic coupling techniques for variance reduction. Here we demonstrate that these two methods can be combined and deployed together by means of a new sensitivity bound which incorporates the variance of the quantity of interest as well as the Fisher Information Matrix estimated from the first method. The first step of the proposed strategy labels sensitivities using the bound and screens out the insensitive parameters in a controlled manner. In the second step of the proposed strategy, a finite-difference method is applied only for the sensitivity estimation of the (potentially) sensitive parameters that have not been screened out in the first step. Results on an epidermal growth factor network with fifty parameters and on a protein homeostasis with eighty parameters demonstrate that the proposed strategy is able to quickly discover and discard the insensitive parameters and in the remaining potentially sensitive parameters it accurately estimates the sensitivities. The new sensitivity strategy can be several times faster than current state-of-the-art approaches that test all parameters, especially in "sloppy" systems. In particular, the computational acceleration is quantified by the ratio between the total number of parameters over the number of the sensitive parameters. PMID- 26161545 TI - An Appeal to the Global Health Community for a Tripartite Innovation: An "Essential Diagnostics List," "Health in All Policies," and "See-Through 21(st) Century Science and Ethics". AB - Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an "Essential Diagnostics List." Additionally, we explain the ways in which adopting a vision for "Health in All Policies" could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, "see through" taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20(th) century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public-private partnerships, as it underscores the fact that scientific knowledge is a co product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations. PMID- 26161547 TI - Hybrid Lithium-Sulfur Batteries with a Solid Electrolyte Membrane and Lithium Polysulfide Catholyte. AB - Lithium-sulfur (Li-S) batteries are receiving great attention as the most promising next-generation power source with significantly high charge-storage capacity. However, the implementation of Li-S batteries is hampered by a critical challenge because of the soluble nature of the intermediate polysulfide species in the liquid electrolyte. The use of traditional porous separators unavoidably allows the migration of the dissolved polysulfide species from the cathode to the lithium-metal anode and results in continuous loss of capacity. In this study, a LiSICON (lithium super ionic conductor) solid membrane is used as a cation selective electrolyte for lithium-polysulfide (Li-PS) batteries to suppress the polysulfide diffusion. Ionic conductivity issue at the lithium metal/solid electrolyte interface is successfully addressed by insertion of a "soft", liquid electrolyte integrated polypropylene interlayer. The solid LiSICON lithium-ion conductor maintains stable ionic conductivity during the electrochemical cycling of the cells. The Li-PS battery system with a hybrid solid/liquid electrolyte exhibits significantly enhanced cyclability relative to the cells with the traditional liquid-electrolyte integrated porous separator. PMID- 26161546 TI - Variations in DREB1A and VP1.1 Genes Show Association with Salt Tolerance Traits in Wild Tomato (Solanum pimpinellifolium). AB - Association analysis was conducted in a core collection of 94 genotypes of Solanum pimpinellifolium to identify variations linked to salt tolerance traits (physiological and yield traits under salt stress) in four candidate genes viz., DREB1A, VP1.1, NHX1, and TIP. The candidate gene analysis covered a concatenated length of 4594 bp per individual and identified five SNP/Indels in DREB1A and VP1.1 genes explaining 17.0% to 25.8% phenotypic variation for various salt tolerance traits. Out of these five alleles, one at 297 bp in DREB1A had in-frame deletion of 6 bp (CTGCAT) or 12 bp (CTGCATCTGCAT), resulting in two alleles, viz., SpDREB1A_297_6 and SpDREB1A_297_12. These alleles individually or as haplotypes accounted for maximum phenotypic variance of about 25% for various salt tolerance traits. Design of markers for selection of the favorable alleles/haplotypes will hasten marker-assisted introgression of salt tolerance from S. pimpinellifolium into cultivated tomato. PMID- 26161548 TI - Bifidobacterium pseudocatenulatum CECT 7765 Reduces Obesity-Associated Inflammation by Restoring the Lymphocyte-Macrophage Balance and Gut Microbiota Structure in High-Fat Diet-Fed Mice. AB - BACKGROUND/OBJECTIVES: The role of intestinal dysbiosis in obesity-associated systemic inflammation via the cross-talk with peripheral tissues is under debate. Our objective was to decipher the mechanisms by which intervention in the gut ecosystem with a specific Bifidobacterium strain reduces systemic inflammation and improves metabolic dysfunction in obese high-fat diet (HFD) fed mice. METHODS: Adult male wild-type C57BL-6 mice were fed either a standard or HFD, supplemented with placebo or Bifidobacterium pseudocatenulatum CECT 7765, for 14 weeks. Lymphocytes, macrophages and cytokine/chemokine concentrations were quantified in blood, gut, liver and adipose tissue using bead-based multiplex assays. Biochemical parameters in serum were determined by ELISA and enzymatic assays. Histology was assessed by hematoxylin-eosin staining. Microbiota was analyzed by 16S rRNA gene pyrosequencing and quantitative PCR. RESULTS: B. pseudocatenulatum CECT 7765 reduced obesity-associated systemic inflammation by restoring the balance between regulatory T cells (Tregs) and B lymphocytes and reducing pro-inflammatory cytokines of adaptive (IL-17A) and innate (TNF-alpha) immunity and endotoxemia. In the gut, the bifidobacterial administration partially restored the HFD-induced alterations in microbiota, reducing abundances of Firmicutes and of LPS-producing Proteobacteria, paralleled to reductions in B cells, macrophages, and cytokines (IL-6, MCP-1, TNF-alpha, IL-17A), which could contribute to systemic effects. In adipose tissue, bifidobacterial administration reduced B cells whereas in liver the treatment increased Tregs and shifted different cytokines (MCP-1 plus ILP-10 in adipose tissue and INF-gamma plus IL 1beta in liver). In both tissues, the bifidobacteria reduced pro-inflammatory macrophages and, TNF-alpha and IL-17A concentrations. These effects were accompanied by reductions in body weight gain and in serum cholesterol, triglyceride, glucose and insulin levels and improved oral glucose tolerance and insulin sensitivity in obese mice. CONCLUSIONS: Here, we provide evidence of the immune cellular mechanisms by which the inflammatory cascade associated with diet induced obesity is attenuated by the administration of a specific Bifidobacterium strain and that these effects are associated with modulation of gut microbiota structure. PMID- 26161549 TI - Health Literacy and Health-Related Quality of Life Among a Population-Based Sample of Cancer Patients. AB - Health-related quality of life is an important outcome in cancer care. A few studies indicate that health literacy influences cancer patients' health-related quality of life, but additional investigation is needed. The authors examined the relation between health literacy and health-related quality of life among cancer patients. A cross-sectional survey was conducted with cancer patients in Wisconsin during 2006-2007. Data on sociodemographics, clinical characteristics, health-related quality of life, and health literacy were obtained from the state's cancer registry and a mailed questionnaire. Regression analyses were used to characterize the association between health-related quality of life and health literacy. The study sample included 1,841 adults, newly diagnosed with lung, breast, colorectal, or prostate cancer in 2004 (response rate = 68%). Health related quality of life was measured with the Functional Assessment of Cancer Therapy-General. Adjusting for confounders, higher health literacy was associated with greater health-related quality of life (p < .0001). Controlling for covariates, we found significant differences between those in the highest and lowest health literacy categories (p < .0001) and in the physical (p < .0001), functional (p < .0001), emotional (p < .0001), and social (p = .0007) well-being subscales. These associations exceeded the minimally important difference threshold for overall health-related quality of life and functional well-being. Health literacy is positively and independently associated with health-related quality of life among cancer patients. These findings support adoption of health literacy best practices by cancer care systems. PMID- 26161552 TI - Detection of Outliers Due to Participants' Non-Adherence to Protocol in a Longitudinal Study of Cognitive Decline. AB - BACKGROUND: Participants' non adherence to protocol affects data quality. In longitudinal studies, this leads to outliers that can be present at the level of the population or the individual. The purpose of the present study is to elaborate a method for detection of outliers in a study of cognitive ageing. METHODS: In the Whitehall II study, data on a cognitive test battery have been collected in 1997-99, 2002-04, 2007-09 and 2012-13. Outliers at the 2012-13 wave were identified using a 4-step procedure: (1) identify cognitive tests with potential non-adherence to protocol, (2) choose a prediction model between a simple model with socio-demographic covariates and one that also includes health behaviours and health measures, (3) define an outlier using a studentized residual, and (4) study the impact of exclusion of outliers by estimating the effect of age and diabetes on cognitive decline. RESULTS: 5516 participants provided cognitive data in 2012-13. Comparisons of rates of annual decline over the first three and all four waves of data suggested outliers in three of the 5 tests. Mean residuals for the 2012-13 wave were larger for the basic compared to the more complex prediction model (all p<0.001), leading us to use the latter for the identification of outliers. Residuals greater than two standard deviation of residuals identified approximately 7% of observations as being outliers. Removal of these observations from the analyses showed that both age and diabetes had associations with cognitive decline similar to that observed with the first three waves of data; these associations were weaker or absent in non-cleaned data. CONCLUSIONS: Identification of outliers is important as they obscure the effects of known risk factor and introduce bias in the estimates of cognitive decline. We showed that an informed approach, using the range of data collected in a longitudinal study, may be able to identify outliers. PMID- 26161553 TI - Examining Two Sets of Introgression Lines in Rice (Oryza sativa L.) Reveals Favorable Alleles that Improve Grain Zn and Fe Concentrations. AB - In the modern world, the grain mineral concentration (GMC) in rice (Oryza sativa L.) not only includes important micronutrient elements such as iron (Fe) and zinc (Zn), but it also includes toxic heavy metal elements, especially cadmium (Cd) and lead (Pb). To date, the genetic mechanisms underlying the regulation of GMC, especially the genetic background and G * E effects of GMC, remain largely unknown. In this study, we adopted two sets of backcross introgression lines (BILs) derived from IR75862 (a Zn-dense rice variety) as the donor parent and two elite indica varieties, Ce258 and Zhongguangxiang1, as recurrent parents to detect QTL affecting GMC traits including Fe, Zn, Cd and Pb concentrations in two environments. We detected a total of 22 loci responsible for GMC traits, which are distributed on all 12 rice chromosomes except 5, 9 and 10. Six genetic overlap (GO) regions affecting multiple elements were found, in which most donor alleles had synergistic effects on GMC. Some toxic heavy metal-independent loci (such as qFe1, qFe2 and qZn12) and some regions that have opposite genetic effects on micronutrient (Fe and Zn) and heavy metal element (Pb) concentrations (such as GO-IV) may be useful for marker-assisted biofortification breeding in rice. We discuss three important points affecting biofortification breeding efforts in rice, including correlations between different GMC traits, the genetic background effect and the G * E effect. PMID- 26161550 TI - The Clinicopathologic and Prognostic Value of Altered Chromosome 17 Centromere Copy Number in HER2 Fish Equivocal Breast Carcinomas. AB - Chromosome 17 centromere (CEP17) gain is frequently observed in breast cancer by fluorescence in situ hybridization (FISH). To address the biologic characteristics and clinical significance of CEP17 gain in a large population of breast cancer patients, we performed FISH on a series of 770 breast cancer tissues to evaluate the status of human epidermal growth factor receptor 2 (HER2) gene and CEP17 by immunohistochemistry (IHC) and FISH. Among the 770 specimens, 184 cases showed CEP17 gain (23.9%). Histological grade, nodal status, HER2 by IHC, Ki 67 index, and p53 expression were significantly different between CEP17 gain tumors and HER2-positive tumors. In contrast with HER2-negative tumors, CEP17 gain tumors showed higher histological grade, higher HER2 score by IHC, and higher Ki 67 index. The patients with CEP17 gain tumors had an intermediate survival between HER2-negative and HER2-positive patients. By comparison to HER2 negative and HER2-positive patients, survival in luminal B patients with CEP17 gain tumors also fell in between. In conclusion, CEP17 gain tumors show specific differences compared with HER2-negative and HER2-positive tumors in clinical parameters and prognosis. PMID- 26161554 TI - Changes in the Incidence of Congenital Anomalies in Henan Province, China, from 1997 to 2011. AB - AIM: To investigate changes in incidence and characteristics of congenital anomalies in infants in Henan Province of China over a period of 15 years. METHODS: Population-based surveillance in Henan Province was conducted from 1997 to 2011 in 75 hospitals (40 urban districts and 35 rural counties, comprising about 20% of the total births). Basic population information was obtained from the healthcare network. All live births, intrauterine deaths after 28 weeks, and stillbirths were included. Congenital anomalies were diagnosed and reported to Henan Provincial Maternal and Pediatric Healthcare Hospital. RESULTS: Of 1,815,920 births from 1997 to 2011, 15,660 cases of congenital anomalies were identified, resulting in an average incidence of 86.2 cases per 10,000 births. The incidence of congenital anomalies showed a significant downward trend (p < 0.0001) in rural areas and the whole province (p < 0.0001), but an increase in urban areas (p = 0.003). The incidence was much higher in rural than in urban areas in 1997, but this discrepancy decreased rapidly and no difference was seen between rural and urban areas in 2003. The incidence in females was higher than in males in 1997-1999 but decreased to a similar level as that in males in 2000. Maternal age exceeding 35 years was associated with a higher incidence of congenital anomalies. Among the 23 types of congenital anomalies recorded, neural tube defects were the most common; the incidence declined from 39.3 cases per 10,000 births in 1997 to 6.1 cases per 10,000 births in 2011. CONCLUSION: The incidence of congenital anomalies has decreased in Henan Province over the past 15 years due to significant reductions in rural areas and among girls. This decrease was partly related to a reduction in neural tube defects that was likely the result of a folic acid intervention in the province. PMID- 26161555 TI - Magnetic Resonance Imaging Characteristics of Ovarian Clear Cell Carcinoma. AB - PURPOSE: To probe the magnetic resonance imaging (MRI) features of ovarian clear cell carcinoma (OCCC). METHODS: This study retrospectively collected MRI data for 21 pathology-confirmed OCCCs from 19 female patients. The MRI findings were analyzed to determine the tumor size, shape/edge, shape and number of protrusions within the cyst, cystic or necrotic components, signal intensity (SI) and enhancement features. RESULTS: The age of the 19 patients ranged from 28 to 63 years (mean age: 53 years). Unilateral tumors were found in 17 patients (17/19, 89%); the average size of all tumors was 10.8 cm. The tumors on MRI were classified into two categories: (a) "cystic adnexal mass with solid protrusions" in 12 (57%) and (b) "solid adnexal mass with cystic areas or necrosis" in 9 (43%). For group a, high to very high SI was observed for most tumors (10/12, 83%) on T1-weighted images (T1WIs), and very high SI was observed on T2-weighted images (T2WIs) for all 12 tumors. Most solid protrusions were irregular and few in number and exhibited heterogeneous intermediate SI on T1WIs and T2WIs and prolonged enhanced SI in the contrast study. All 9 OCCCs in group b were predominantly solid masses with unequally sized necrotic or cystic areas in which some cysts were located at the periphery of the tumor (4/9, 44%). The solid components in all 9 tumors showed iso- or slightly high SI on T1WIs, heterogeneous iso-high SI on T2WIs and heterogeneous prolonged enhancement. According to FIGO classification, 14 tumors (14/19, 74%) were stages I-II, and 5 (5/19, 26%) were stages III-IV. CONCLUSIONS: On MRI, OCCCs present as large unilateral multilocular or unilocular cystic masses with irregular intermediate SI solid protrusions or predominantly solid masses with cysts or necrosis at an early FIGO stage. PMID- 26161556 TI - Epidemiology and Genetic Characterization of Noroviruses among Adults in an Endemic Setting, Peruvian Amazon Basin, 2004-2011. AB - BACKGROUND: Successful vaccination strategies against norovirus will require understanding the burden of disease and relevant genotypes in populations. However, few data are available from cohort studies of adults living in low- and middle-income countries (LMIC). MATERIALS AND METHODS: We conducted a nested case control study within a Peruvian military cohort to characterize the burden of norovirus infection, predominant genotypes, and associated symptoms from 2004 through 2011. Randomly selected case and control stools were tested for norovirus, bacteria, and parasites. The odds ratio of the association between norovirus infection and diarrhea was estimated using multiple logistic regression and co-infection adjusted attributable fractions were calculated. RESULTS: Of the 3,818 cohort study participants, 624 developed diarrhea. Overall and norovirus associated diarrhea incidence rates were 42.3 and 6.0 per 100 person-years, respectively. The most prevalent norovirus genogroup was GII (72.5%, 29/40), which was associated with diarrhea (AOR 3.4, 95% CI: 1.3-8.7, P = 0.012). The co infection adjusted GII attributable fraction was 6.4%. DISCUSSION: Norovirus was a frequent cause of diarrhea in an adult population followed longitudinally in an LMIC setting. Vaccine strategies should consider targeting adults in endemic settings and special populations that could serve as community transmission sources. PMID- 26161557 TI - Mutagenesis Study Reveals the Rim of Catalytic Entry Site of HDAC4 and -5 as the Major Binding Surface of SMRT Corepressor. AB - Histone deacetylases (HDACs) play a pivotal role in eukaryotic gene expression by modulating the levels of acetylation of chromatin and related transcription factors. In contrast to class I HDACs (HDAC1, -2, -3 and -8), the class IIa HDACs (HDAC4, -5, -7 and -9) harbor cryptic deacetylases activity and recruit the SMRT HDAC3 complex to repress target genes in vivo. In this regard, the specific interaction between the HDAC domain of class IIa HDACs and the C-terminal region of SMRT repression domain 3 (SRD3c) is known to be critical, but the molecular basis of this interaction has not yet been addressed. Here, we used an extensive mutant screening system, named the "partitioned one- plus two-hybrid system", to isolate SRD3c interaction-defective (SRID) mutants over the entire catalytic domains of HDAC4 (HDAC4c) and -5. The surface presentation of the SRID mutations on the HDAC4c structure revealed that most of the mutations were mapped to the rim surface of the catalytic entry site, strongly suggesting this mutational hot spot region as the major binding surface of SRD3c. Notably, among the HDAC4c surface residues required for SRD3c binding, some residues (C667, C669, C751, D759, T760 and F871) are present only in class IIa HDACs, providing the molecular basis for the specific interactions between SRD3c and class IIa enzymes. To investigate the functional consequence of SRID mutation, the in vitro HDAC activities of HDAC4 mutants immuno-purified from HEK293 cells were measured. The levels of HDAC activity of the HDAC4c mutants were substantially decreased compared to wild-type. Consistent with this, SRID mutations of HDAC4c prevented the association of HDAC4c with the SMRT-HDAC3 complex in vivo. Our findings may provide structural insight into the binding interface of HDAC4 and -5 with SRD3c, as a novel target to design modulators specific to these enzymes. PMID- 26161558 TI - Elimination of Onchocerciasis from Mexico. AB - BACKGROUND: Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS) surveys were undertaken which employed entomological indicators to check for transmission recrudescence. METHODOLOGY/PRINCIPAL FINDINGS: In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP) was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L3/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population. CONCLUSIONS/SIGNIFICANCE: The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico. PMID- 26161559 TI - Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. AB - BACKGROUND: Single-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT. OBJECTIVES: To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique. METHODS: One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012) at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA>= 100 copies/MUL (Viroseq). Sequencing was performed with ABI 3100 (Applied Biosystems). Logistic regression modelling was undertaken to identify the factors associated with NVP RAM. RESULTS: Seventy-nine children had their samples genotyped. Their median age was 7.0 (3-12) months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs) for PMTCT. ARV RAM were detected in 43 (54.4%) of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93-186.34) and with mother's CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02-9.32). In the multivariable analysis the mother's exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33-253.66). CONCLUSIONS: We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers' exposure to PMTCT significantly increased the risk of NVP RAM. PMID- 26161561 TI - Iconic Meaning in Music: An Event-Related Potential Study. AB - Although there has been extensive research on the processing of the emotional meaning of music, little is known about other aspects of listeners' experience of music. The present study investigated the neural correlates of the iconic meaning of music. Event-related potentials (ERP) were recorded while a group of 20 music majors and a group of 20 non-music majors performed a lexical decision task in the context of implicit musical iconic meaning priming. ERP analysis revealed a significant N400 effect of congruency in time window 260-510 ms following the onset of the target word only in the group of music majors. Time-course analysis using 50 ms windows indicated significant N400 effects both within the time window 410-460 ms and 460-510 ms for music majors, whereas only a partial N400 effect during time window 410-460 ms was observed for non-music majors. There was also a trend for the N400 effects in the music major group to be stronger than those in the non-major group in the sub-windows of 310-360 ms and 410-460 ms. Especially in the sub-window of 410-460 ms, the topographical map of the difference waveforms between congruent and incongruent conditions revealed different N400 distribution between groups; the effect was concentrated in bilateral frontal areas for music majors, but in central-parietal areas for non music majors. These results imply probable neural mechanism differences underlying automatic iconic meaning priming of music. Our findings suggest that processing of the iconic meaning of music can be accomplished automatically and that musical training may facilitate the understanding of the iconic meaning of music. PMID- 26161562 TI - Comparing Happiness and Hypomania Risk: A Study of Extraversion and Neuroticism Aspects. AB - Positive affect has long been considered a hallmark of subjective happiness. Yet, high levels of positive affect have also been linked with hypomania risk: a set of cognitive, affective, and behavioral characteristics that constitute a dispositional risk for future episodes of hypomania and mania. At a personality level, two powerful predictors of affective experience are extraversion and neuroticism: extraversion has been linked to positive affect, and neuroticism to negative affect. As such, a single personality trait--extraversion--has been linked to both beneficial and harmful outcomes associated with positivity. It is clear that positive affect, in different forms, has divergent consequences for well-being, but previous research has struggled to articulate the nature of these differences. We suggest that the relationship between affect and well-being needs to be situated within the psychological context of the individual--both in terms of more specific forms of extraversion and neuroticism, but also in terms of interactions among personality aspects. Consistent with this idea, we found that two aspects of extraversion (enthusiasm and assertiveness) differentially predicted subjective happiness from hypomania risk and two aspects of neuroticism (volatility and withdrawal) interacted to predict hypomania risk: the highest levels of hypomania risk were associated with the combination of high volatility and low withdrawal. These findings underscore the importance of examining personality at the right level of resolution to understand well-being and dysfunction. PMID- 26161560 TI - Quantitative Analysis of MicroRNAs in Vaccinia virus Infection Reveals Diversity in Their Susceptibility to Modification and Suppression. AB - Vaccinia virus (VACV) is a large cytoplasmic DNA virus that causes dramatic alterations to many cellular pathways including microRNA biogenesis. The virus encodes a poly(A) polymerase which was previously shown to add poly(A) tails to the 3' end of cellular miRNAs, resulting in their degradation by 24 hours post infection (hpi). Here we used small RNA sequencing to quantify the impact of VACV infection on cellular miRNAs in human cells at both early (6 h) and late (24 h) times post infection. A detailed quantitative analysis of individual miRNAs revealed marked diversity in the extent of their modification and relative change in abundance during infection. Some miRNAs became highly modified (e.g. miR-29a 3p, miR-27b-3p) whereas others appeared resistant (e.g. miR-16-5p). Furthermore, miRNAs that were highly tailed at 6 hpi were not necessarily among the most reduced at 24 hpi. These results suggest that intrinsic features of human cellular miRNAs cause them to be differentially polyadenylated and altered in abundance during VACV infection. We also demonstrate that intermediate and late VACV gene expression are required for optimal repression of some miRNAs including miR-27-3p. Overall this work reveals complex and varied consequences of VACV infection on host miRNAs and identifies miRNAs which are largely resistant to VACV-induced polyadenylation and are therefore present at functional levels during the initial stages of infection and replication. PMID- 26161564 TI - Complex Questions Rarely Have Simple Answers. PMID- 26161563 TI - Semi-analytical model for output factor calculations in proton beam therapy with consideration for the collimator aperture edge. AB - In the development of an external radiotherapy treatment planning system, the output factor (OPF) is an important value for the monitor unit calculations. We developed a proton OPF calculation model with consideration for the collimator aperture edge to account for the dependence of the OPF on the collimator aperture and distance in proton beam therapy. Five parameters in the model were obtained by fitting with OPFs measured by a pinpoint chamber with the circular radiation fields of various field radii and collimator distances. The OPF model calculation using the fitted model parameters could explain the measurement results to within 1.6% error in typical proton treatment beams with 6- and 12 cm SOBP widths through a range shifter and a circular aperture more than 10.6 mm in radius. The calibration depth dependences of the model parameters were approximated by linear or quadratic functions. The semi-analytical OPF model calculation was tested with various MLC aperture shapes that included circles of various sizes as well as a rectangle, parallelogram, and L-shape for an intermediate proton treatment beam condition. The pre-calculated OPFs agreed well with the measured values, to within 2.7% error up to 620 mm in the collimator distance, though the maximum difference was 5.1% in the case of the largest collimator distance of 740 mm. The OPF calculation model would allow more accurate monitor unit calculations for therapeutic proton beams within the expected range of collimator conditions in clinical use. PMID- 26161565 TI - Endoscopic retrograde cholangiopancreatography (ERCP) outcomes can improve after further training for an individual already experienced in ERCP. AB - This study was carried out to assess the impact of therapeutic endoscopy training on the endoscopic retrograde cholangiopancreatography (ERCP) practice of a physician who was practicing ERCP for many years in a community setting in the United States. A retrospective chart review of 390 ERCPs performed by the physician was accomplished; 176 and 214 ERCPs were performed before and after undergoing therapeutic endoscopy training respectively. Rates of common bile duct cannulation; postprocedure pancreatitis; use of common bile duct and pancreatic stents, as well as frequency of biliary and pancreatic sphincterotomies were assessed. The rate of common bile duct cannulation increased from 87% to 96% (P=0.008), while post-ERCP pancreatitis decreased from 8% to 3% (P=0.056), demonstrating that further guided experience in ERCP improved technical competency and decreased complications of ERCP for a physician already performing ERCPs independently in the USA. PMID- 26161566 TI - A single dose of prophylactic antibiotic may be sufficient to prevent postprocedural infection in upper endosonography guided fiducial marker placement. AB - AIM: Prophylactic antibiotic after endosonographic ultrasound (EUS) guided fiducial marker placement is common practice to prevent infection. Duration of using prophylaxis antibiotic is unknown. The aim of this paper was to assess whether one time intraprocedural administration of a prophylactic antibiotic is sufficient to prevent infection after EUS guided fiducial marker placement. METHODS: Retrospective study was performed included all adult patients who underwent EUS guided fiducial markers over 18 month period. Procedure related infection was defined as any infection not directly attributable to any other cause within 30 days of the procedure. The patients followed up with the Gastroenterology clinic in one week and with Radiation Oncology clinic weekly after undergoing EUS guided fiducial marker placement. RESULTS: A total of 35 upper EUS-guided fiducial markers were placed during 20 procedures on 18 patients. The average age of patients was 59 years. There were 10 females and 8 males.. All patients received one dose of cephalosporin, amoxicillin, clindamycin or levoflocaxin. The fiducial markers were deployed in different organs. None of the patients developed any infections due to the procedure. CONCLUSION: This study suggests that one dose of intravenous antibiotic administered intraprocedurally is sufficient to prevent infection related to upper EUS guided fiducial marker placement. PMID- 26161567 TI - Sleep disturbances in hepatitis C patients undergoing treatment: minisleep questionnaire as a screening tool. AB - AIM: Sleep disturbances are frequently reported by patients with chronic hepatitis C virus (HCV) during treatment with interferon (IFN) alpha plus ribavirin. Poor sleep quality is related to the onset of depression and impaired quality of life in patients receiving treatment. The aims of this study were to apply the Mini Sleep Questionnaire (MSQ) as a screening tool to assess the self reported sleep quality and the prevalence of sleep disorders. METHODS: We conducted a transversal, observational, descriptive study comprising 41 subjects with HCV, divided into two groups, treatment (N.=16) and control (N.=25). A structured questionnaire was used to collect sociodemographic and clinical data and the MSQ was applied to assess the sleep quality. A Chi-square test was applied to compare sleep quality between groups. RESULTS: Significant differences between groups in the classification of sleep quality were observed (P<0.05). The group of patients under treatment presented higher frequency of sleep disorders (63%) when compared to the control group (12%). Additionally, the apnea domain was the most impacted. CONCLUSION: This study identified a higher prevalence of sleep disorders and self-reported poor sleep quality in HCV patients under treatment. The MSQ may be useful as a screening tool for sleep disorders in HCV patients during the treatment with IFN-alpha plus ribavirin. PMID- 26161568 TI - The relationship between the prevalence of Helicobacter pylori and serum levels of vitamin B12 in women 10-49 years. AB - AIM: The aim of this study was to determine the relationship between serum vitamin B12 and Helicobacter(H.) pylori prevalence in women between 10-49 years. METHODS: This cross-sectional (descriptive and analytical) study was conducted in the city of Samirom located in Isfahan, Iran in 2013. The population studied consisted of 100 women between 10-49 years and they were selected by convenience sampling. Data collection tools was checklist in which its content validity and reliability were confirmed. The data were entered into SPSS 16 software and were analyzed using descriptive statistics methods and univariate and multivariate inferential statistics methods. RESULTS: The mean age of the study population was 29.5 +/- 1.04. Also 29% of the population studied was infected with H. pylori, and prevalence of serum vitamin B12 less than 160 was 47%. After adjusted the effect of confounder variables with multivariate logistic regression analysis, the odds of infected with H. pylori in peoples with vitamin B12 less than 160, was 4.8 times the peoples with vitamin B12 normal (Equal and greater than 160) that this different was statistically significant (P<0.001). CONCLUSION: The results showed that serum levels of vitamin B12 is a determinant factor in the prevalence of H. pylori. PMID- 26161569 TI - Factors associated with elevated serum alanine aminotransferase in patients with type 1 diabetes mellitus. AB - AIM: Metabolic syndrome and type 2 diabetes are associated with insulin resistance and hepatic steatosis, which are common causes of alanine aminotransferase (ALT) elevation. This study aims to identify variables associated with altered ALT in type 1 diabetic (DM1) subjects. METHODS: A cross sectional study conducted in the outpatient endocrinology clinic of a university hospital. Patients with DM1 were seen between December 2012 and September 2013; clinical variables were collected from medical records. RESULTS: Fifty-six patients were included aged 27 +/- 10.1 years; 60.7% were men. The study subjects exhibited an average ALT of 36.7 +/- 10.3 U/L (median = 35 U/L) and their average Body Mass Index (BMI) was 23.8 +/- 3.8 kg/m2. When comparing individuals with elevated ALT > 35 U/L (N. = 27) with those ALT <= 35 U/L (N. = 29), we found that individuals with ALT values > 35 U/L showed a higher proportion of men (77.8% vs. 44.8%, P = 0.012) and a higher mean age (30.2 +/- 12.3 vs. 24.6 +/- 6.9 years, P = 0.046). When new ALT reference values were applied (19 U/L for women and 30 U/L for men), five individuals had normal ALT values. Individuals with elevated ALT had higher BMI (24.3 vs. 20.9; P = 0.036), fasting glucose (194.8 +/- 101.2 vs. 123.6 +/- 42.0 mg/dL; P = 0.013) and higher HbA1c (9.9 +/- 2.8 vs. 7.8 +/- 0.7%; P < 0.001) levels. In Pearson correlation analysis, ALT values correlated with HbA1c (r = 0.285; P = 0.033). CONCLUSION: In patients with DM1, elevated ALT values are associated with BMI, fasting glucose and HbA1c. PMID- 26161570 TI - Hepatorenal syndrome after treatment of visceral leishmaniasis requiring terlipressin therapy. PMID- 26161571 TI - Clinical utility of recently published clinical and endoscopic predictors of diagnosis of gastrointestinal Kaposi sarcoma. PMID- 26161572 TI - Durable hemostasis after embolization for massive arterial bleeding after percutaneous radiologic gastrostomy: salvage of original gastrostomy tube for enteral feeding for eight months after embolization. PMID- 26161574 TI - Directly Connected AzaBODIPY-BODIPY Dyad: Synthesis, Crystal Structure, and Ground- and Excited-State Interactions. AB - Directly connected, strongly interacting sensitizer donor-acceptor dyads mimic light-induced photochemical events of photosynthesis. Here, we devised a dyad composed of BF2-chelated dipyrromethene (BODIPY) directly linked to BF2-chelated tetraarylazadipyrromethene (azaBODIPY) through the beta-pyrrole position of azaBODIPY. Structural integrity of the dyad was arrived from two-dimensional NMR spectral studies, while single-crystal X-ray structure of the dyad provided the relative orientation of the two macrocycles to be ~62 degrees . Because of direct linking of the two entities, ultrafast energy transfer from the (1)BODIPY* to azaBODIPY was witnessed. A good agreement between the theoretically estimated Forster energy transfer rate and experimentally determined rate was observed, and this rate was found to be higher than that reported for BODIPY-azaBODIPY analogues connected with spacer units. In agreement with the free-energy calculations, the product of energy transfer, (1)azaBODIPY* revealed additional photochemical events such as electron transfer leading to the creation of BODIPY(*+)-azaBODIPY(*-) radical ion pair, more so in polar benzonitrile than in nonpolar toluene, as evidenced by femtosecond transient spectroscopic studies. Additionally, the spectral, electrochemical, and photochemical studies of the precursor compound azaBODIPY-dipyrromethane also revealed occurrence of excited state events. In this case, electron transfer from the (1)azaBODIPY* to dipyrromethane (DPM) yielded DPM(*+)-azaBODIPY(*-) charge-separated state. The study described here stresses the role of close association of the donor and acceptor entities to promote ultrafast photochemical events, applicable of building fast-response optoelectronic and energy-harvesting devices. PMID- 26161573 TI - Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss. AB - BACKGROUND: Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss. OBJECTIVES: We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy. METHODS: Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss. RESULTS: Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: -0.5 days (95% CI: -0.9, -0.1), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: -0.8 days (95% CI: -1.2, -0.4), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.02), p = 0.001]. CONCLUSIONS: BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle-specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2 ethyl-5-oxohexyl) phthalate] and SigmaDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies. PMID- 26161575 TI - Toward Two-Dimensional All-Carbon Heterostructures via Ion Beam Patterning of Single-Layer Graphene. AB - Graphene has many claims to fame: it is the thinnest possible membrane, it has unique electronic and excellent mechanical properties, and it provides the perfect model structure for studying materials science at the atomic level. However, for many practical studies and applications the ordered hexagon arrangement of carbon atoms in graphene is not directly suitable. Here, we show that the atoms can be locally either removed or rearranged into a random pattern of polygons using a focused ion beam (FIB). The atomic structure of the disordered regions is confirmed with atomic-resolution scanning transmission electron microscopy images. These structural modifications can be made on macroscopic scales with a spatial resolution determined only by the size of the ion beam. With just one processing step, three types of structures can be defined within a graphene layer: chemically inert graphene, chemically active amorphous 2D carbon, and empty areas. This, along with the changes in properties, gives promise that FIB patterning of graphene will open the way for creating all-carbon heterostructures to be used in fields ranging from nanoelectronics and chemical sensing to composite materials. PMID- 26161576 TI - Theoretical Studies on Hexanuclear Oxometalates [M6L19](q-) (M = Cr, Mo, W, Sg, Nd, U). Electronic Structures, Oxidation States, Aromaticity, and Stability. AB - We here report a systematic theoretical study on geometries, electronic structures, and energetic stabilities of six hexanuclear polyoxometalates [M6O19](2-) of the six-valence-electron metals including the d-elements M = Cr, Mo, W, Sg from group 6 and the f-elements M = Nd, U. Scalar relativistic density functional theory was applied to these clusters in vacuum and in solution. It is shown that the Oh Lindqvist structure of the isolated [M6O19](2-) units with hexavalent M elements (M(+6)) is only stable for the three heavy transition metals M = Mo, W, and Sg. The rare Th symmetry is predicted for M = U both in vacuum and in solution, owing to pseudo-Jahn-Teller distortion of these closed shell systems. The Oh and Th structures correspond to cyclic "aromatic" U-O-U and alternating U=O-U bonding of cross-linked U4O4 rings, respectively. The reduced [U6O19](8-) cluster with pentavalent U(+5) also shows Th symmetry in vacuum, but Oh symmetry in a dielectric environment. The occurrence of different structures for varying fractional oxidation states in different environments is rationalized. Theoretical investigation of the recently synthesized U(+5) complex [U6O13L6](0) (L6 = tetracyclopentadienyl dibipyridine) shows a distorted Th-type symmetry, too. The stabilities of these complexes of different metal oxidation states are consistent with the general periodic trends of oxidation states. PMID- 26161577 TI - Fast Crystal Growth in o-Terphenyl Glasses: A Possible Role for Fracture and Surface Mobility. AB - Molecular liquids can develop a fast mode of crystal growth ("GC growth") near the glass transition temperature. This phenomenon remains imperfectly understood with several explanations proposed. We report that GC growth in o-terphenyl conserves the overall volume, despite a 5% higher density of the crystal, and produces fine crystal grains with the same unit cell as normally grown crystals. These results indicate that GC growth continuously creates voids and free surfaces, possibly by fracture. This aspect of the phenomenon has not been considered by previous treatments and is a difficulty for those models that hypothesize a 5% strain without voids. Given the existence of even faster crystal growth on the free surface of molecular glasses, we consider the possibility that GC growth is facilitated by fracture and surface mobility. This notion has support from the fact that GC growth and surface growth are both highly correlated with surface diffusivity and with fast crystal growth along preformed cracks in the glass. PMID- 26161578 TI - Activable Cell-Penetrating Peptide Conjugated Prodrug for Tumor Targeted Drug Delivery. AB - In this paper, an activable cell-penetrating peptide (CR8G3PK6, ACPP) with a shielding group of 2,3-dimethylmaleic anhydride (DMA) was conjugated with antitumor drug doxorubicin (DOX) to construct a novel prodrug (DOX-ACPP-DMA) for tumor targeted drug delivery. The shielding group of DMA linked to the primary amines of K6 through the amide bond was used to block the cell-penetrating function of the polycationic CPP (R8) through intramolecular electrostatic attraction at physiological pH 7.4. At tumor extracellular pH 6.8, the hydrolysis of DMA led to charge reversal, activating the pristine function of CPP for improved cellular uptake by tumor cells. Confocal laser scanning microscopy (CLSM) and flow cytometry studies revealed that the cellular uptake of DOX-ACPP DMA was significantly enhanced after acid-triggered activation in both HeLa and COS7 cells. After cell internalization, the overexpressed intracellular proteases would further trigger drug release in cells. Both in vitro and in vivo investigations showed that the peptidic prodrug exhibited significant tumor growth inhibition and demonstrated great potential for tumor therapy. PMID- 26161579 TI - Convenient and Precise Strategy for Mapping N-Glycosylation Sites Using Microwave Assisted Acid Hydrolysis and Characteristic Ions Recognition. AB - N-glycosylation is one of the most prevalence protein post-translational modifications (PTM) which is involved in several biological processes. Alternation of N-glycosylation is associated with cellular malfunction and development of disease. Thus, investigation of protein N-glycosylation is crucial for diagnosis and treatment of disease. Currently, deglycosylation with peptide N glycosidase F is the most commonly used technique in N-glycosylation analysis. Additionally, a common error in N-glycosylation site identification, resulting from protein chemical deamidation, has largely been ignored. In this study, we developed a convenient and precise approach for mapping N-glycosylation sites utilizing with optimized TFA hydrolysis, ZIC-HILIC enrichment, and characteristic ions of N-acetylglucosamine (GlcNAc) from higher-energy collisional dissociation (HCD) fragmentation. Using this method, we identified a total of 257 N glycosylation sites and 144 N-glycoproteins from healthy human serum. Compared to deglycosylation with endoglycosidase, this strategy is more convenient and efficient for large scale N-glycosylation sites identification and provides an important alternative approach for the study of N-glycoprotein function. PMID- 26161580 TI - Adsorption Properties of Triethylene Glycol on a Hydrated {1014} Calcite Surface and Its Effect on Adsorbed Water. AB - Molecular dynamics (MD) and Born-Oppenheimer MD (BOMD) simulations were employed to investigate adsorption of aqueous triethylene glycol (TEG) on a hydrated {1014} calcite surface at 298 K. We analyzed the orientation of TEG adsorbed on calcite, as well as the impact of TEG on the water density and adsorption free energy. The adsorption energies of TEG, free energy profiles for TEG, details of hydrogen bonding between water and adsorbed TEG, and dihedral angle distribution of adsorbed TEG were estimated. We found that while the first layer of water was mostly unaffected by the presence of adsorbed TEG, the density of the second water layer was decreased by 71% at 75% surface coverage of TEG. TEG primarily attached to the calcite surface via two adjacent adsorption sites. Hydrogen bonds between water and adsorbed TEG in the second layer almost exclusively involved the hydroxyl oxygen of TEG. The adsorption energy of TEG on calcite in a vacuum environment calculated by classical MD amounted to 217 kJ/mol, which agreed very well with estimates found by using BOMD. Adsorption on hydrated calcite yielded a drastically lower value of 33 kJ/mol, with the corresponding adsorption free energy of 55.3 kJ/mol, giving an entropy increase of 22.3 kJ/mol due to adsorption. We found that the presence of TEG resulted in a decreased magnitude of the adsorption free energy of water, thus decreasing the calcite wettability. This effect can have a profound effect on oil and gas reservoir properties and must be carefully considered when evaluating the risk of hydrate nucleation. PMID- 26161581 TI - Diameter-Specific Growth of Semiconducting SWNT Arrays Using Uniform Mo2C Solid Catalyst. AB - Semiconducting single-walled nanotube (s-SWNT) arrays with specific diameters are urgently demanded in the applications in nanoelectronic devices. Herein, we reported that by using uniform Mo2C solid catalyst, aligned s-SWNT (~90%) arrays with narrow-diameter distribution (~85% between 1.0 and 1.3 nm) on quartz substrate can be obtained. Mo2C nanoparticles with monodisperse sizes were prepared by using molybdenum oxide-based giant clusters, (NH4)42[Mo132O372(H3CCOO)30(H2O)72].10H3CCOONH4.300H2O(Mo132), as the precursor that was carburized by a gas mixture of C2H5OH/H2 during a temperature-programmed reduction. In this approach, the formation of volatile MoO3 was inhibited due to the annealing and reduction at a low temperature. As a result, uniform Mo2C nanoparticles are formed, and their narrow size-dispersion strictly determines the diameter distribution of SWNTs. During the growth process, Mo2C selectively catalyzes the scission of C-O bonds of ethanol molecules, and the resultant absorbed oxygen (Oads) preferentially etches metallic SWNTs (m-SWNTs), leading to the high-yield of s-SWNTs. Raman spectroscopic analysis showed that most of the s SWNTs can be identified as (14, 4), (13, 6), or (10, 9) tubes. Our findings open up the possibility of the chirality-controlled growth of aligned-SWNTs using uniform carbide nanoparticles as solid catalysts for practical nanoelectronics applications. PMID- 26161582 TI - Synthesis of Pyrroles through Rhodium(III)-Catalyzed Reactions of Allylamines and Alkenes. AB - Pyrrole derivatives are generated in reactions of allylamines with alkenes that are promoted by a Rh(III) catalyst in the presence of AgOAc. This process, which involves chelation assisted C-H bond activation and N-annulation, is applied to a three step synthesis of Zomepirac. PMID- 26161584 TI - Surface-Controlled Properties of Myosin Studied by Electric Field Modulation. AB - The efficiency of dynamic nanodevices using surface-immobilized protein molecular motors, which have been proposed for diagnostics, drug discovery, and biocomputation, critically depends on the ability to precisely control the motion of motor-propelled, individual cytoskeletal filaments transporting cargo to designated locations. The efficiency of these devices also critically depends on the proper function of the propelling motors, which is controlled by their interaction with the surfaces they are immobilized on. Here we use a microfluidic device to study how the motion of the motile elements, i.e., actin filaments propelled by heavy mero-myosin (HMM) motor fragments immobilized on various surfaces, is altered by the application of electrical loads generated by an external electric field with strengths ranging from 0 to 8 kVm(-1). Because the motility is intimately linked to the function of surface-immobilized motors, the study also showed how the adsorption properties of HMM on various surfaces, such as nitrocellulose (NC), trimethylclorosilane (TMCS), poly(methyl methacrylate) (PMMA), poly(tert-butyl methacrylate) (PtBMA), and poly(butyl methacrylate) (PBMA), can be characterized using an external field. It was found that at an electric field of 5 kVm(-1) the force exerted on the filaments is sufficient to overcome the frictionlike resistive force of the inactive motors. It was also found that the effect of assisting electric fields on the relative increase in the sliding velocity was markedly higher for the TMCS-derivatized surface than for all other polymer-based surfaces. An explanation of this behavior, based on the molecular rigidity of the TMCS-on-glass surfaces as opposed to the flexibility of the polymer-based ones, is considered. To this end, the proposed microfluidic device could be used to select appropriate surfaces for future lab on-a-chip applications as illustrated here for the almost ideal TMCS surface. Furthermore, the proposed methodology can be used to gain fundamental insights into the functioning of protein molecular motors, such as the force exerted by the motors under different operational conditions. PMID- 26161583 TI - Modulating Molecular Chaperones Improves Mitochondrial Bioenergetics and Decreases the Inflammatory Transcriptome in Diabetic Sensory Neurons. AB - We have previously demonstrated that modulating molecular chaperones with KU-32, a novobiocin derivative, ameliorates physiologic and bioenergetic deficits of diabetic peripheral neuropathy (DPN). Replacing the coumarin core of KU-32 with a meta-fluorinated biphenyl ring system created KU-596, a novobiocin analogue (novologue) that showed neuroprotective activity in a cell-based assay. The current study sought to determine whether KU-596 offers similar therapeutic potential for treating DPN. Administration of 2-20 mg/kg of KU-596 improved diabetes induced hypoalgesia and sensory neuron bioenergetic deficits in a dose dependent manner. However, the drug could not improve these neuropathic deficits in diabetic heat shock protein 70 knockout (Hsp70 KO) mice. To gain further insight into the mechanisms by which KU-596 improved DPN, we performed transcriptomic analysis of sensory neuron RNA obtained from diabetic wild-type and Hsp70 KO mice using RNA sequencing. Bioinformatic analysis of the differentially expressed genes indicated that diabetes strongly increased inflammatory pathways and that KU-596 therapy effectively reversed these increases independent of Hsp70. In contrast, the effects of KU-596 on decreasing the expression of genes regulating the production of reactive oxygen species were more Hsp70-dependent. These data indicate that modulation of molecular chaperones by novologue therapy offers an effective approach toward correcting nerve dysfunction in DPN but that normalization of inflammatory pathways alone by novologue therapy seems to be insufficient to reverse sensory deficits associated with insensate DPN. PMID- 26161585 TI - Recyclable Capture and Destruction of Aqueous Micropollutants Using the Molecule Specific Cavity of Cyclodextrin Polymer Coupled with KMnO4 Oxidation. AB - The removal of aqueous micropollutants remains challenging because of the interference of natural water constituents that are typically 3-9 orders of magnitude more concentrated. Cyclodextrins, which feature molecular recognition and are widely applied in separation and catalysis, are promising materials in the development of pollutant treatment technologies. Here, we described the facile integration of cyclodextrin polymer (CDP) adsorption and KMnO4 oxidation for recyclable capture and destruction of aqueous micropollutants (i.e., antibiotics and TBBPA). CDP exhibited adsorption efficiencies of 0.81-88% and 0.81-94% toward 14 pollutants at 50.0 ng/L and 50.0 MUg/L, respectively, at a solid-to-liquid ratio of 1:1250. The presence of simulated or natural water constituents (e.g., Mg(2+), Ca(2+), DOC, and a combination thereof) did not decrease the adsorption potential of CDP toward these pollutants because the pollutants, based on molecular specificity, were entrapped in the CD cavity. Subsequent KMnO4 oxidation completely degraded the retained pollutants, demonstrating that the pollutants could be broken down in the cavity. Pristine CDP was rearranged into the structurally loose composites that featured a porous CDP architecture with uniform embedment of delta-MnO2 nanoparticles and different adsorption efficiencies. delta-MnO2 loading was a linear function of the number of times the integrated procedure was repeated, underlying the accurate control of CDP recycling. Thus, this approach may represent a new method for the removal of aqueous micropollutants. PMID- 26161586 TI - Detection of water contamination from hydraulic fracturing wastewater: a MUPAD for bromide analysis in natural waters. AB - Due to the rapid expansion in hydraulic fracturing (fracking), there is a need for robust, portable and specific water analysis techniques. Early detection of contamination is crucial for the prevention of lasting environmental damage. Bromide can potentially function as an early indicator of water contamination by fracking waste, because there is a high concentration of bromide ions in fracking wastewaters. To facilitate this, a microfluidic paper-based analytical device (MUPAD) has been developed and optimized for the quantitative colorimetric detection of bromide in water using a smartphone. A paper microfluidic platform offers the advantages of inexpensive fabrication, elimination of unstable wet reagents, portability and high adaptability for widespread distribution. These features make this assay an attractive option for a new field test for on-site determination of bromide. PMID- 26161587 TI - Quantitative assessment of the carbocation/carbene character of the gold-carbene bond. AB - The geometric perturbation of the cyclopropyl ring in [LAu(S)](n+) (S = cyclopropyl(methoxy)carbene) complexes has been recently proposed as an indirect experimental probe of the [LAu](n+) electron-donating power, but experimental data are available only for a phosphine ligand [Brooner et al., Chem. Commun., 2014, 50, 2420, L = P(t-Bu)2(o-biphenyl)]. We broaden the study through DFT geometry optimization of a large number of systems, including anionic, neutral and cationic ligands. We combine these results with the accurate calculation, through charge displacement analysis, of the Dewar-Chatt-Duncanson components of the Au-carbene bond. The results demonstrate a linear correlation between the distortion of the cyclopropyl ring (Deltad) and the Au -> C pi back-donation, which enables us to confidently estimate back-donation from a simple geometry optimization or, when available, from experimental data such as X-ray crystal structures. Consequently, Deltad can be reliably used to quantitatively determine the position of each system in the continuum between the carbocationic and carbene extremes and the percentage of back-donation that S is able to accept (Pback). In particular, Pback results to be vanishing with cationic ligands, between 18 and 27% with neutral phosphines and carbenes and around 50% with anionic ligands. Finally, we study the effect of the heteroatom on the substrate, showing that the absolute value of the back-donation is enhanced by around 25% when the methoxy is substituted by a methyl group. Despite this, since the absence of the heteroatom also enhances the maximum capacity of the carbene to accept back-donation, the position of the systems in the continuum moves only slightly toward the carbene end. PMID- 26161588 TI - Calibration of Clinical Audio Recording and Analysis Systems for Sound Intensity Measurement. AB - PURPOSE: Sound intensity is an important acoustic feature of voice/speech signals. Yet recordings are performed with different microphone, amplifier, and computer configurations, and it is therefore crucial to calibrate sound intensity measures of clinical audio recording and analysis systems on the basis of output of a sound-level meter. This study was designed to evaluate feasibility, validity, and accuracy of calibration methods, including audiometric speech noise signals and human voice signals under typical speech conditions. METHOD: Calibration consisted of 3 comparisons between data from 29 measurement microphone-and-computer systems and data from the sound-level meter: signal specific comparison with audiometric speech noise at 5 levels, signal-specific comparison with natural voice at 3 levels, and cross-signal comparison with natural voice at 3 levels. Intensity measures from recording systems were then linearly converted into calibrated data on the basis of these comparisons, and validity and accuracy of calibrated sound intensity were investigated. RESULTS: Very strong correlations and quasisimilarity were found between calibrated data and sound-level meter data across calibration methods and recording systems. CONCLUSIONS: Calibration of clinical sound intensity measures according to this method is feasible, valid, accurate, and representative for a heterogeneous set of microphones and data acquisition systems in real-life circumstances with distinct noise contexts. PMID- 26161589 TI - Does Health Insurance Premium Exemption Policy for Older People Increase Access to Health Care? Evidence from Ghana. AB - Aging in Sub-Saharan Africa causes major challenges for policy makers in social protection. Our study focuses on Ghana, one of the few Sub-Saharan African countries that passed a National Policy on Aging in 2010. Ghana is also one of the first Sub-Saharan African countries that launched a National Health Insurance Scheme (NHIS; NHIS Act 650, 2003) with the aim to improve access to quality health care for all citizens, and as such can be considered as a means of poverty reduction. Our study assesses whether premium exemption policy under the NHIS that grants non-payments of annual health insurance premiums for older people increases access to health care. We assessed differences in enrollment coverage among four different age groups (18-49, 50-59, 60-69, and 70+). We found higher enrollment for the 70+ and 60-69 age groups. The likelihood of enrollment was 2.7 and 1.7 times higher for the 70+ and 60-69 age groups, respectively. Our results suggest the NHIS exemption policy increases insurance coverage of the aged and their utilization of health care services. PMID- 26161590 TI - Predictors of heavy drinking after liver transplantation for alcoholic liver disease in Denmark (1990-2013): a nationwide study with competing risks analyses. AB - OBJECTIVE: Heavy drinking following liver transplantation decreases survival. Little is known of predictors of heavy drinking, which should guide clinicians identifying patients at high risk of return to heavy drinking after transplantation. MATERIAL AND METHODS: We calculated the cumulative incidence of heavy drinking among patients transplanted for alcoholic liver disease in Denmark 1990-2013. We then analyzed pre-transplant demographic and psychiatric characteristics as predictors of post-transplant heavy drinking. Information was obtained from medical records, from nationwide registries and by interview. RESULTS: Among 156 liver-transplanted patients, the cumulative incidence of heavy drinking was 18%, 24% and 27% after 5, 10 and 15 years post-transplant. In univariate analyses of pre-transplant predictors of heavy drinking after transplantation, younger age (p < 0.001), being retired (p = 0.007), anxiety (p = 0.04), personality disorder (p = 0.05) and no lifetime diagnosis of alcohol dependence (p = 0.03) were associated with heavy drinking after transplantation. Smoking (p = 0.06) tended to be associated, whereas depression (p = 0.7) or being married was not (p = 0.7). In the multivariate analysis, only younger age (p = 0.03), being retired (p = 0.007) and no lifetime diagnosis of alcohol dependence (p = 0.003) remained significant predictors. Heavy drinking after transplantation decreased survival beyond 5 years post-transplant (p = 0.004). CONCLUSIONS: There is a high incidence of heavy drinking after liver transplantation for alcoholic cirrhosis in Denmark. Younger age, being retired and no lifetime diagnosis of alcohol dependence were predictors of heavy drinking after transplantation. PMID- 26161591 TI - Choosing drugs for the treatment of diabetic neuropathy. AB - INTRODUCTION: Diabetic sensorimotor polyneuropathy (DSP) affects 50% of diabetes patients and is painful in about 26%. Although disease-modifying therapies are not available for DSP, symptomatic treatments for painful diabetic neuropathy (PDN) are effective. AREAS COVERED: We performed a MEDLINE search on PubMed using the search terms: treatment diabetic neuropathy and treatment PDN. This review outlines the problem posed by DSP, the clinical presentation and the characterization of PDN. A discussion of disease-modifying interventions, including the benefits of strict glycemic control, is followed by a focus on interventions for PDN including antidepressants, anticonvulsants and other treatments. EXPERT OPINION: Disease modification in DSP remains an unmet need in clinical medicine affecting a large percentage of the population with concomitant healthcare costs. Strict glycemic control and attention to potential risk factors such as hypertension, hyperlipidemia and obesity may minimize DSP. Many patients benefit from treatment of their painful symptoms with anticonvulsants or antidepressants, but all are associated with significant side effects that limit their usefulness. There is a need for treatments of PDN with fewer side effects and more effective pain relief. PMID- 26161592 TI - Transcriptomic analysis of skeletal muscle from beef cattle exposed to illicit schedules containing dexamethasone: identification of new candidate biomarkers and their validation using samples from a field monitoring trial. AB - Growth promoters (GPs) such as the glucocorticoid dexamethasone (DEX) and the beta-adrenergic agonist clenbuterol (CLEN) are still used abusively in beef cattle production. Transcriptomic markers for indirect detection of such GPs have been discussed in either experimentally treated animals or commercial samples separately. In the present study we examine the transcriptomic signature of DEX alone or in combination with CLEN in skeletal muscle of experimentally treated beef cattle, and, furthermore, compare them with previously screened commercial samples from a field-monitoring study, as well as with proteomics data representing the same set of samples. Using DNA microarray technology, transcriptomic profiling was performed on 12 samples representing three groups of animals: DEX (0.75 mg/animal/day, n = 4), a combination of DEX (0.66 mg/animal/day) and CLEN (from 2 to 6 mg/animal/day, n = 4) and a control group (n = 4). Analyses showed the differential expression of 198 and 39 transcripts in DEX and DEX-CLEN groups, respectively. Both groups had no common modulated genes in between, neither with the proteomics data. Sixteen candidate genes were validated via qPCR. They showed high correlation with the corresponding microarray data. Principal component analysis (PCA) on both the qPCR and normalised microarray data resulted in the separation of treated animals from the untreated ones. Interestingly, all the PCA plots grouped the DEX-positive samples (experimental or commercial) apart from each other. In brief, this study provides some interesting glucocorticoid-responsive biomarkers whose expression was contradictory to what is reported in human studies. Additionally, this study points out the transcriptomic signature dissimilarity between commercial and experimentally treated animals. PMID- 26161593 TI - Feasibility of an iPad application for studying menopause-related symptom clusters and women's heuristics. AB - PURPOSE: To evaluate feasibility, including usability and utility, of the Computerized Symptom Capture Tool for Menopause (C-SCAT-M), a symptom heuristics application (app) for the iPad, with midlife women. METHODS: Thirty midlife women aged 40-60 and experiencing symptoms they associated with menopause were recruited through flyers posted on a university campus, primary care and women's health clinics. The C-SCAT-M guided participants to identify symptoms they experienced, draw temporal and causal relationships between symptoms and identify symptom clusters. Women were encouraged to think aloud as they encountered questions or problems and their comments were audio recorded. After completing the C-SCAT-M, they completed a 22-item acceptability survey and a demographic survey. Data were downloaded from catalyst website and analyzed using SPSS. RESULTS: Women completed the C-SCAT-M with minimal difficulty, with most indicating that using the app was very/extremely easy and most (57%) preferred using the iPad app to paper. Most women stated that the final diagrams were very/extremely accurate depictions of their symptom clusters and relationships (77%). CONCLUSION: The C-SCAT-M demonstrated initial feasibility, including usability and utility, for collecting data about symptom clusters experienced by midlife women. PMID- 26161595 TI - Comparison of the anti-diabetic effects of resveratrol, gliclazide and losartan in streptozotocin-induced experimental diabetes. AB - AIM: The aim of this study was to compare the effect of the resveratrol with gliclazide and losartan in streptozotocin induced diabetic rats. MATERIALS AND METHODS: Adult male Wistar albino rats were divided into five groups of seven rats each. Diabetes was induced with a single intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg). Rats with blood glucose levels above 250 mg/dl after 48 h of streptozotocin injection were included in the diabetic group. Gliclazide and resveratrol were administered for 3 weeks at 5 mg/kg per day and losartan was administered for 3 weeks at 30 mg/kg per day in an oral aqueous suspension. At the end of the third week all rats were euthanized and fasting blood glucose, HbA1c and the metabolic activity of the hepatic enzymes hexokinase and glucose-6 phosphate dehydrogenase were measured in tail blood and liver specimens. All parameters were quantified using an ELISA plate reader. RESULTS: Resveratrol and gliclazide significantly reduced both blood glucose levels and HbA1c levels in diabetic rats (p < 0.001). However, losartan did not exhibit the same effects (p < 0.05). The enzymatic activity of the liver enzymes hexokinase, glucose-6 phosphate dehydrogenase, fructose 1,6-biphosphatase, pyruvate kinase and glucose 6 phosphatase were enhanced by resveratrol and gliclazide, while losartan treatment was not associated with significant changes in liver carbohydrate metabolism. CONCLUSION: Resveratrol was not effective in improving liver carbohydrate metabolism relative to gliclazide, a drug widely used to treat diabetes. Dose-response profile of resveratrol remains indeterminate and additional studies may be necessary to determine effective dosing in diabetes. PMID- 26161596 TI - The Noncompacted Folding of Proteins by Modified Elastic Net Algorithm. AB - In this article, a protein sequence of length n is embedded in a two-dimensional lattice with m (>n) points. Thus the obtained minimal energy configurations are expected to have flexible shapes in contrast to the compact rectangular conformations. To fulfill this extension, the elastic net algorithm is modified to deal with the difficulty brought by the unsymmetrical relationship between amino acids and lattice points. New set partition strategy in the embedding phase is introduced, and two local search methods are applied to overcome the multimapping phenomena. Several HP benchmark examples with up to 48 amino acids are tested to verify the effectiveness of the proposed approach. PMID- 26161597 TI - A Dynamic Programming Algorithm For (1,2)-Exemplar Breakpoint Distance. AB - The exemplar breakpoint distance problem is motivated by finding conserved sets of genes between two genomes. It asks to find respective exemplars in two genomes to minimize the breakpoint distance between them. If one genome has no repeated gene (called trivial genome) and the other has genes repeating at most twice, it is referred to as the (1, 2)-exemplar breakpoint distance problem, EBD(1, 2) for short. Little has been done on algorithm design for this problem by now. In this article, we propose a parameter to describe the maximum physical span between two copies of a gene in a genome, and based on it, design a fixed-parameter algorithm for EBD(1, 2). Using a dynamic programming approach, our algorithm can take O(4(s)n(2)) time and O(4(s)n) space to solve an EBD(1, 2) instance that has two genomes of n genes where the second genome has each two copies of a gene spanning at most s copies of the genes. Our algorithm can also be used to compute the maximum adjacencies between two genomes. The algorithm has been implemented in C++. Simulations on randomly generated data have verified the effectiveness of our algorithm. The software package is available from the authors. PMID- 26161598 TI - Communicating with the New Generations. The Challenge for Pediatric Dentists. AB - Most of the children and parents are virtuous and will give us plenty of reasons to enjoy what we do. Unfortunately, we all know that something is somehow wrong with these new generations. Parents and children sometimes place Pediatric dentists in a dilemma. The social structure changes every few years causing a burden on how to deal with these families. For this reason, dentists might decide to sedate or go to the operating room when these children might be potentially good dental patients. Deciding this course of action, does not allow us to bond with them. Bonding with children must be worked and nurtured. This is part of what pediatric dentists are trained for. This manuscript will illustrate the major changes seen with the new generations of parents and children and how it affects us the way we work in our offices. We will show the importance of bonding with parents and children, moving beyond the biological aspects and venturing into the psycho-socio and cultural issues. Knowing our children and adolescents will allow us to detect potential physical or emotional hazardous behavior. PMID- 26161599 TI - Evidence-based Update of Pediatric Dental Restorative Procedures: Dental Materials. AB - BACKGROUND: The science of dental materials and restorative care in children and adolescent is constantly evolving, and the ongoing search for ideal restorative materials has led to plethora of research. AIM: To provide an evidence base to assist dental practitioners choose appropriate restorative care for children and adolescents. STUDY DESIGN: This evidence-based review appraises this literature, primarily between the years 1995-2013, for efficacy of dental amalgam, composites, glass ionomer cements, compomers, preformed metal crowns and anterior esthetic restorations. The assessment of evidence for each dental material was based on a strong evidence, evidence in favor, expert opinion, and evidence against by consensus of the authors. RESULTS: There is varying level of evidence for the use of restorative materials like amalgam, composites, glass ionomers, resin-modified glass-ionomers, compomers, stainless steel crowns and anterior crowns for both primary and permanent teeth. CONCLUSIONS: A substantial amount data is available on restorative materials used in pediatric dentistry; however, there exists substantial evidence from systematic reviews and randomized clinical trials and clinicians need to examine and understand the available literature evidence carefully to aid them in clinical decision making. PMID- 26161600 TI - Fluoride Varnish Application in the Primary Care Setting. A Clinical Study. AB - OBJECTIVES: The study objectives were twofold: 1. To examine how an intervention to apply fluoride varnish (FV) in a primary health setting to all young, low income children was implemented and sustained and 2. To assess the feasibility of tracking medical care utilization in this population. STUDY DESIGN: The study included children age 1-5, insured through a government program, seen (7/1/2010 4/30/2012). Data on age, race, sex, clinic encounter, eligibility for and receipt of FV was obtained. The level of data in primary care, specialty care, urgent care and hospitalizations to assess feasibility of future patient tracking was also acquired.. RESULTS: Of 12,067 children, 85% received FV. Differences were found by age (youngest had highest rates). Small differences by race (81%-88%, highest in Blacks.) was found. No differences were found by sex. Ability to track over time was mixed. Approximately 50% had comprehensive data. However, primary care visit and hospitalization data was available on a larger percentage. CONCLUSIONS: FV programs can be introduced in the primary care setting and sustained. Further, long-term follow up is possible. Future study of such cohorts capturing health and cost benefits of oral health prevention efforts is needed. PMID- 26161601 TI - Clinical Evaluation of Restorative Materials in Primary Teeth Class II Lesions. AB - OBJECTIVE: The aim of this study was to evaluate clinical success of primary teeth class II lesions restored with different restorative materials [Hybrid Composite Resin (HCR), Resin Modified Glass Ionomer Cement (RMGIC), compomer, and Giomer Composite Resin (GCR)] followed up for 24 months. STUDY DESIGN: This study was carried out on 146 primary molars of 41 children in the age range of 5-7 years. The class II lesions in primary molars of a patient were restored using different restorative materials. Restorations were evaluated according to FDI criteria and their survival rates were determined. Data were analysed with Pearson chi-square, Kaplan-Meier and Wilcoxon (Breslow) tests (alpha = 0.05). RESULTS: The failure rates of restorative materials were as follows: compomer 33.3%, RMGIC 28.1%, HCR 22.5% and GCR 21.1%. CONCLUSIONS: While the functional failure was the most important factor in restorative material failure, RMGIC was the most successful material in terms of biological evaluation criterion and GCR had the longest survival rate. PMID- 26161602 TI - Self-Esteem and Oral Condition of Institutionalized Abused Children in Japan. AB - OBJECTIVE: Abused children have been reported to have low self-esteem. The aim of this study was to investigate the effects of dental intervention on self-esteem, oral condition, and concern for oral health in abused children admitted to a child protection service facility. STUDY DESIGN: We examined the oral condition of 65 children (34 boys, 31 girls; aged 2-15 years), instructed them in tooth brushing. Self-esteem was examined using Pope's five-scale test for children. Before discharge, the children completed questionnaires on concern about their oral health. RESULTS: The findings revealed the reasons for admission were child abuse and neglect (n=45), domestic violence against the mother (n= 20), special needs (n=11), delinquency (n=7), school refusal (n=2), and other reasons (n=3). Thirty-five of the 65 residents (54%) needed treatment for caries. Of these, 24 (69%) were abused children and 11 (31%) were admitted due to other reasons. Mean self-esteem score differed significantly between the resident children (n=43) and an outpatient control group (n=102) (59.16+/-14.54 vs 73.92+/-16.81, respectively; p<0.01). CONCLUSION: Although the abused children had low self esteem, after dental intervention, positive answers regarding oral health were obtained. The findings suggest that dental interventions might be effective for helping to improve the self-esteem of abused children. PMID- 26161603 TI - Early Colonization of Lactobacillus reuteri after Exposure to Probiotics. AB - The aim of the present in vivo animal study is to investigate the ability of L. reuteri to colonize the oral flora during infancy. STUDY DESIGN: Twenty four rats, aged 1 month, which were pre-analyzed for mutans streptococci and L. reuteri absence in their saliva, were randomly divided into 3 groups. The control group was infected with S. mutans ATCC 25175 at the 2nd month, three times a day for 14 days. S. mutans counts were determined with microbiological saliva analyzes obtained by standard methods of oral swabbing at 3rd, 4th and 5th months. The second group, Probiotic I group, was also infected with S. mutans at the 2nd month, and further infected with L. reuteri ATCC 55730 (1*10(8)),5 drops per day for 25 days, at the 3rd month. S. mutans and L. reuteri counts were determined at the 3rd, 4th and 5th months. Plates were incubated anaerobically at 37 degrees C for 48 h, after which colonies were confirmed as L. Reuteri. RESULTS: Regarding intragroup analysis, S. mutans counts of the Control group increased steadily during the 3rd. and 4th. months, and a statistically significant (p<0.05) reduction was registered at the 5. month. S. mutans counts of the Probiotic I group increased steadily during the 3rd. and 4th. months, and again a statistically significant (p<0.05) reduction, parallel with the Control group, was registered at the 5th. month. In the Probiotic II group, S. mutans counts started at a higher level than the Control group and there was a statistically significant (p<0.05) reduction of S. mutans at the 5th. month. CONCLUSION: It may be concluded that, L. reuteri promised a better colonization as a 'first colonisation strain'. PMID- 26161604 TI - Dental Caries Status, Socio-Economic, Behavioral and Biological Variables among 12-Year-Old Palestinian School Children. AB - There are currently inadequate data regarding the prevalence of dental caries and its associated variables, among Palestinian children. AIM: To determine the current prevalence of dental caries and related variables, among Palestinian children in East Jerusalem. STUDY DESIGN: A stratified sample of 286 East Jerusalem Palestinian children was selected, employing randomly chosen sixth grade clusters from three pre-selected socio-economic school groups. Dental caries was recorded according to WHO recommendations. Salivary flow, pH, buffer capacity and microbial parameters, were recorded according to previously employed methodologies. RESULTS: The mean level of caries experience, by DMFT, was 1.98 +/ 2.05. This level was higher than those found among Israeli children, but lower than several other Middle Eastern countries. In uni-variate analysis, significant associations were revealed between caries and school categories, which indicated lower, middle and higher socio-economic position(SEP), mothers' employment, home densities, dental visits, tooth brushing, Streptococci mutans (SM), Lactobacilli (LB), and saliva pH. CONCLUSION: According to a linear logistic regression model, children learning in lower SEP schools, with higher SM levels and more acidic saliva, had a higher chance of experiencing dental caries. These findings should be considered in the planning of services and dental health care programs for Palestinian children. PMID- 26161605 TI - Dental Erosion and its Associated Factors In 11-16-Year Old School Children. AB - Dental erosion currently stands as a great challenge for the clinician, regarding the diagnosis, identification of the etiological factors, prevention and execution of an adequate treatment. AIMS: To evaluate the prevalence, severity, and associated factors on dental erosion in 11-16-years old. STUDY DESIGN: A cross sectional study was conducted among 2000 school children who were randomly selected. A questionnaire was given to the children that included personal demographic details and habit of consuming acidic foods and drinks. An index specific for dental erosion given by O Sullivan was used to assess every affected tooth. The values were subjected to chi-square test and multivariate logistic regression analysis. RESULTS: The prevalence of dental erosion was found to be 1.4%. Females (1.6%) were slightly more affected than males (1.3%). Public school children (2.1%) were found to be affected a little more than private children (0.7%). Chi square test showed significant association between type of school and erosion prevalence (p = 0.015). Most commonly affected teeth were lateral incisor (59.72%). CONCLUSION: The prevalence of dental erosion was found to be low when compared to various studies done all over the world. PMID- 26161606 TI - Salivary Lysozyme in Relation to Dental Caries among Thai Preschoolers. AB - AIM: The objective of this study was to analyze salivary lysozyme levels and activities in Thai preschoolers with different dental caries status. STUDY DESIGN: Unstimulated saliva samples were collected from 64 preschoolers, divided into a caries free group (n = 32) and a severe early childhood caries (S-ECC) group (n = 32). RESULTS: Both groups were similar regarding gender, age, dental caries status, salivary flow rate, and salivary protein concentrations. No differences were also in the caregivers' characteristics, oral health behaviors, and feeding habits. Only professional fluoride application was less frequently found in the S-ECC group (p < 0.03). Western blotting and lysoplate assays revealed that salivary lysozyme levels and activities were significantly increased in the S-ECC group compared with the caries free group (p< 0.001; p = 0.008, respectively). CONCLUSION: The up-regulated expression of salivary lysozyme and the increased lysozyme activity in S-ECC preschoolers suggests a possible connection between salivary lysozyme and oral immunity in response to early childhood dental caries. PMID- 26161607 TI - Enamel Deproteinization using Papacarie and 10% Papain Gel on Shear Bond Strength of Orthodontic Brackets Before and After Acid Etching. AB - OBJECTIVE: To suggest Papacarie((r)) as a new deproteinizing agent in comparison with indigenously prepared 10% papain gel before and after acid etching that may enhance the quality of the bond between enamel surface and composite resin complex. STUDY DESIGN: One hundred and twenty five extracted human premolars were utilized and divided into five groups: In the group 1, enamel surface was etched and primer was applied. In group 2, treatment with papacarie((r)) for 60 seconds followed by etching and primer application. In group 3, etching followed by treatment with papacarie((r)) for 60 seconds and primer application. In group 4, treatment with 10% papain gel for 60 seconds followed by etching and primer application. In group 5, etching followed by treatment with 10% papain gel for 60 seconds and primer application . After bonding the brackets, the mechanical testing was performed using a Universal testing machine. The failure mode was analyzed using an adhesive remnant index. The etching patterns before and after application of papacarie((r)) and 10% papain gel was also evaluated using SEM. The values obtained for shear bond strength were submitted to analysis of variance and Tukey test (p < 0.05). RESULTS: It was observed that group 2 and group 4 had the highest shear bond strength and was statistically significant from other groups (p=0.001). Regarding Adhesive remnant index no statistical difference was seen between the groups (p=0.538). CONCLUSION: Papacarie((r)) or 10% papain gel can be used to deproteinize the enamel surface before acid etching to enhance the bond strength of orthodontic brackets. PMID- 26161608 TI - Salivary Urease and ADS Enzymatic Activity as Endogenous Protection against Dental Caries in Children. AB - The aim of this cross sectional study was to evaluate the ureolytic and arginolytic activities of saliva in children and associate them with their caries status. STUDY DESIGN: 65, 8 year old children, were randomly selected. The ureolytic and arginolytic activity of non stimulated saliva was studied and associated with DMFT and dmft index. Saliva of children were sampled under fasting conditions; Children refrained from any oral hygiene procedures during the 12 hours that preceded the sample collection. Caries activity was scored and divided in 3 groups: Group A: Index zero: without lesions; Group B: Moderate Index: 1 to 3 enamel caries lesions; and Group C: High Index: more than 4 dentin caries lesions. RESULTS: DMFT scores were moderate: 0.4(+/-0.79) and dmft: 2.78(+/-2.45). Results expressed in MUmol/min/mg/protein, for urease activity were statistically significant (p=0.048): Group A= 0.69 (+/-0.7); Group B= 0.45 (+/-0.43); and Group C= 0.39 (+/-0.55). The arginine deiminase activity was not statistically significant (p=0.16): Group A= 2.53 (+/-1.42), Group B= 2.31 (+/ 1.57) and Group C= 1.97 (+/-2.0). CONCLUSION: Higher levels of ureolytic (statistically significant) and arginolytic activity (trend) in saliva were associated with lower DMFT/dmft scores in 8 year old children. There was a higher production of ammonia from the arginine deiminase system than the urease enzyme in saliva (p>0.05). PMID- 26161609 TI - Remineralization Capacity of Three Fissure Sealants with and without Gaseous Ozone on Non-Cavitated Incipient Pit and Fissure Caries. AB - OBJECTIVE: The purpose of this study was to investigate the remineralization activation of the application of three fissure sealants (FSs), alone or with gaseous ozone (GO), on non-cavitated initial caries and evaluate the clinical success of FS. STUDY DESIGN: Sixty children who had DIAGNOdent scores between 10 30 on bilateral symmetric mandibular first permanent molars were included in study. In a split-mouth design, teeth were assigned to experimental (with GO) and control (without GO) groups. GO was applied to teeth on one side and then the same brand of randomly selected FSs was applied to the teeth on both sides. Children were divided into 3 groups based on type of FS (Group 1: Aegis {Bosworth Co, North Hamlin Avenue Skokie, Illinois, USA}, Group 2: Fuji Triage {GC, Tokyo, Japan}, Group 3: Helioseal {Ivoclar Vivadent, Liechtenstein, Germany}). All FSs were then examined for retention rates at 1, 3, 6, 9, and 12 months; at the end of 12 months, all FSs were removed with an air-abrasion device and DIAGNOdent scores noted to compare with the initial values. RESULTS: The application of GO with either Fuji Triage or Aegis FS was effective on remineralization (p<0.05); however, the application of Helioseal FSs was not effective (p>0.05). The 1(st) and 12(th) months' full retention rates of Fuji Triage FSs was a significant difference (p<0.05) from other FSs (Aegis and Helioseal) (p>0.05). CONCLUSIONS: GO+Aegis FS showed the highest remineralization; and, at the end of 12 months, its clinical success was higher than other FSs. PMID- 26161610 TI - Birth-Weight, Pregnancy Term, Pre-Natal and Natal Complications Related to Child's Dental Anomalies. AB - OBJECTIVES: This cross-sectional study was aimed at determining whether certain pre-natal and natal conditions can predict specific dental anomalies. The conditions observed were: low birth-weight, preterm birth, pre-natal & natal complications. The dental anomalies observed were: enamel defects, total number of decayed, missing and filled teeth (total DMFT), disturbances in the tooth shape and disturbances in the number of teeth. STUDY DESIGN: Out of more than 2000 medical files of children aged 2-17 years old which were reviewed, 300 files met the selection criteria. Information recorded from the files included: age, gender, health status (the ASA physical status classification system by the American Society of Anesthesiologists), birth week, birth weight, total DMFT, hypomineralization, abnormal tooth shape, abnormal number of teeth and hypoplasia. RESULTS: Twenty one children out of 300 (7%) were born after a high risk pregnancy, 25 children (8.3%) were born after high-risk birth, 20 children (6.7%) were born preterm - before week 37, and 29 children (9.7%) were born with a low birth weight (LBW) - 2500 grams or less. A relationship between a preterm birth and LBW to hypomineralization was found. And a relationship between a preterm birth and high-risk pregnancy to abnormal number of teeth was found. No relationship was found between birth (normal/high-risk) and the other parameters inspected. CONCLUSION: Preterm birth and LBW may predict hypomineralization in both primary and permanent dentitions. Furthermore, the study demonstrated that preterm birth and high-risk pregnancy may predict abnormal number of teeth in both dentitions. PMID- 26161611 TI - Levels of Salivary Immunoglobulin A (SIgA) in HIV Infected Children. AB - Secretory IgA is the main type of immunoglobulin in saliva and is considered to be the main secretion factor of adaptive immunity in the mouth. OBJECTIVE: To assess the effect of Anti Retroviral Therapy on SIgA levels in saliva of HIV infected children. STUDY DESIGN: A cross-sectional sample of 50 HIV infected children aged 6-8 years were divided into 2 groups ; Group 1: children prior to onset of anti-retroviral therapy and Group 2: children undergoing anti-retroviral therapy. Stimulated whole saliva samples were collected from each child following I hour of breakfast. The samples were placed on ice packs and immediately transferred to a laboratory, processed and total SIgA quantification was estimated using ELISA. Data obtained was statistically analyzed. RESULTS: Among HIV infected children, significantly low SIgA levels of 6.2 mg/dl was seen in children prior to ART. CONCLUSION: Salivary IgA levels were significantly low in HIV infected children, particularly in children prior to ART. PMID- 26161612 TI - Subcutaneous Midazolam with and without Ketamine for Sedation In Children Undergoing Dental Treatment: A Pilot Study. AB - AIM: The objective of this study was to evaluate the efficacy of subcutaneous (SC) sedation using midazolam with and without ketamine in non-cooperative pediatric patients undergoing dental treatment. STUDY DESIGN: A prospective, randomized, controlled, double-blind, crossover pilot clinical trial was carried out in 13 children, aged between 17-46 months, ASA l, Frankl 1. Two sedation schemes were administered SC: Midazolam alone (M), and a combination of Midazolam Ketamine (MK). Both regimens were administered to the same patient in two consecutive treatment sessions, in accordance with a random assignment. Overall behavior, movement, and crying were assessed according to the modified Houpt scale. Heart rate, blood pressure, blood oxygen saturation, and possible side effects were also monitored. RESULTS: The percentage of non-crying children was always higher in the treatment with MK compared with the treatment with M, but without a significant statistical difference. Regarding variable body movement, the percentage of children without movement was higher in the MK group, although only up to minute 10; no significant differences were found at 20, 30, and 40 minutes, and from minute 40, body movement was lower in the M group. CONCLUSIONS: Midazolam alone and the midazolam-ketamine combination administered subcutaneously resulted in a safe and efficient pharmacological method for providing moderate sedation to non-cooperative pediatric patients undergoing dental treatment. PMID- 26161613 TI - Treatment of Ectopic Permanent Maxillary First Molar Using a K-loop. AB - Ectopic eruption of permanent maxillary first molar can cause root resorption of adjacent primary second molar, thus leading to early loss of primary maxillary second molar. Therefore, it is necessary to correct ectopic maxillary first molar. This case report demonstrates that K-loop can be used as a simple, comfortable, and easier method to correct ectopic eruption of permanent maxillary first molar in existing severe root resorption on adjacent primary second molar. PMID- 26161614 TI - How Do Patients and Parents Decide for Orthodontic Treatment-Effects of Malocclusion, Personal Expectations, Education and Media. AB - OBJECTIVES: To examine patients' and parents' perceptions and expectations from orthodontic treatment. STUDY DESIGN: 491 patients (274 female, 217 male) aged 14 22 years, and 399 parents (245 female, 154 male) completed a questionnaire about preferences, needs and expectations about orthodontic treatment, and scored the present problem. Continuous variables were compared by Mann-Whitney U and Kruskal Wallis tests, whereas Chi-square test was used for categorical variables. RESULTS: Patients'(77.1%) and parents'(84.6%), decision about orthodontic treatments were influenced by suggestion of dentists. Patients who decided to attend to clinic by themselves were higher than parents (p=0.006). Dental aesthetics was the determinant factor for treatment demand for patients(61.0%) and parents(57.3%). Improvement in oral functions was more important for Class III patients than Class I patients (p=0.040). Adult patients/parents with higher education gave more importance to oral functions as well as dental aesthetics (p=0.031). There was no difference among Angle classifications regarding orthodontic problem scores. Parents found media sources valuable (p=0.018) but majority expected dentists for information about orthodontic treatments. Education degree of adult patients/parents effected this decision(p=0.002). CONCLUSIONS: Desire to have better dental aesthetics was the primary motivating factor for all participants. Clinicians should consider concerns of Class III patients about oral functions during treatment planning. PMID- 26161620 TI - Copper Nanowires as Conductive Ink for Low-Cost Draw-On Electronics. AB - This work tackles the complicated problem of clump formation and entanglement of high aspect ratio copper nanowires, due to which a well dispersed solution for use as a true ink for drawable electronics has not been made until now. Through rheology studies even a hard to use material like copper nanowires was tailored to be made into a highly efficient conductive ink with only 2 vol % or 18.28 wt % loading which is far lower than existing nanoparticle based inks. This versatile ink can be applied onto various substrates such as paper, PET, PDMS and latex. By using the ink in a roller ball pen, a bending sensor device was simply drawn on paper, which demonstrated detection of various degrees of convex bending and was highly durable as shown in the 10,000 bending cycling test. A highly sensitive strain sensor which has a maximum gauge factor of 54.38 was also fabricated by simply painting the ink onto latex rubber strip using a paintbrush. Finally a complex conductive pattern depicting the Sydney Opera House was painted on paper to demonstrate the versatility and robustness of the ink. The use of Cu NWs is highly economical in terms of the conductive filler loading in the ink and the cost of copper itself as compared to other metal NPs, CNT, and graphene-based inks. The demonstrated e-ink, devices, and facile device fabrication methods push the field one step closer to truly creating cheap and highly reliable skin like devices "on the fly". PMID- 26161618 TI - A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: A phase I clinical trial. AB - BACKGROUND: A phase Ia/b dose-escalation study was performed to characterize the safety, efficacy and pharmacokinetic properties of the oral small molecule insulin-like growth factor-1-receptor pathway modulator AXL1717 in patients with advanced solid tumors. MATERIAL AND METHODS: This was a prospective, single armed, open label, dose-finding phase Ia/b study with the aim of single day dosing (phase Ia) to define the starting dose for multi-day dosing (phase Ib), and phase Ib to define and confirm recommended phase II dose (RP2D) and if possible maximum tolerated dose (MTD) for repeated dosing. RESULTS AND CONCLUSION: Phase Ia enrolled 16 patients and dose escalations up to 2900 mg BID were successfully performed without any dose limiting toxicity (DLT). A total of 39 patients were treated in phase Ib. AXL1717 was well tolerated with neutropenia as the only dose-related, reversible, DLT. RP2D dose was found to be 390 mg BID for four weeks. Some patients, mainly with NSCLC, demonstrated signs of clinical benefit, including four partial tumor responses (one according to RECIST and three according to PET). The 15 patients with NSCLC with treatment duration longer than two weeks with single agent AXL1717 in third or fourth line of therapy showed a median progression-free survival of 31 weeks and overall survival of 60 weeks. Down-regulation of IGF-1R on granulocytes and increases of free serum levels of IGF-1 were seen in patients treated with AXL1717. AXL1717 had an acceptable safety profile and demonstrated promising efficacy in this heavily pretreated patient cohort, especially in patients with NSCLC. RP2D was concluded to be 390 mg BID for four weeks. Trial number is NCT01062620. PMID- 26161621 TI - Enhancement of High-Density Lipoprotein Cholesterol Functions by Encapsulation of Policosanol Exerts Anti-Senescence and Tissue Regeneration Effects Via Improvement of Anti-Glycation, Anti-Apoptosis, and Cholesteryl Ester Transfer Inhibition. AB - Consumption of policosanol (PCO), a refined mixture of sugar cane wax alcohols, can elevate serum levels of high-density lipoprotein cholesterol (HDL-C), although the molecular mechanism is still unknown. To investigate the mechanism of action responsible for the anti-senescence effects of PCO on lipoprotein metabolism and HDL functionality, we synthesized reconstituted HDL (rHDL) containing PCO. Encapsulation of PCO by rHDL (PCO-rHDL) enhanced anti-oxidant activity against cupric ion-mediated low-density lipoprotein (LDL) oxidation. PCO rHDL (final concentration, 9 MUM PCO) showed more potent anti-oxidant activity than vitamin C treatment (final concentration, 100 MUM). PCO-rHDL inhibited fructose-mediated glycation, which is a major pathological mechanism of diabetic complications, in a dose-dependent manner. PCO also showed cytoprotective effects in monocytes and macrophages with less triggering of apoptotic processes and reactive oxygen species (ROS) production in the presence of hydrogen peroxide (H2O2). PCO-rHDL strongly inhibited uptake of acetylated LDL into macrophages, which is an initial atherosclerotic process. Surprisingly, PCO-rHDL inhibited human serum cholesteryl ester transfer protein (CETP) activity by up to 47% (final concentration, 10 MUM PCO). Subcutaneous injection of PCO-rHDL dose dependently enhanced tissue regeneration activity by 2.4-fold and 3.6-fold compared to that of the phosphate-buffered saline (PBS) control. In conclusion, PCO in HDL showed potent anti-oxidant, anti-glycation, and CETP inhibitory activities along with tissue regenerative activity, especially upon incorporation into HDL. These results suggest that PCO can enhance functionality of HDL in serum to exert anti-senescence and longevity effects. PMID- 26161622 TI - Understanding Health Information Seeking: A Test of the Risk Perception Attitude Framework. AB - The authors used the Risk Perception Attitude framework, which is grounded in the Extended Parallel Process Model, to predict people's intentions to seek health information. In an online survey, 689 participants recruited from a crowdsource website were queried about their anticipated health information seeking, perceived risk, and efficacy in response to four scenarios pertaining to hypertension, hypercholesterolemia, alcohol dependence, and diabetes. Each participant was categorized for each scenario as responsive (higher risk, higher efficacy), avoidant (higher risk, lower efficacy), proactive (lower risk, higher efficacy), or indifferent (lower risk, lower efficacy). As predicted, responsive individuals were more likely to seek information than avoidant individuals, but only in three of the four scenarios. Also as expected, there was no difference between proactive and indifferent individuals' likelihood of seeking health information for any scenario. Risk and efficacy, while significant predictors of anticipated health information seeking, left much of the variance unexplained. An analysis of the reasons for information seeking and nonseeking among nonconforming cases suggests that a wider range of influences on health information seeking should be investigated, including curiosity, prior knowledge, social expectations, and situational norms. PMID- 26161623 TI - Comparing Advanced Practice Providers and Physicians as Providers of e-Visits. AB - BACKGROUND: Although electronic delivery (electronic visits [e-visits]) of healthcare services by advanced practice providers (APPs) is growing, literature defining the roles of different providers and comparing outcomes is lacking. We analyzed two e-visit models at the University of Pittsburgh Medical Center (UPMC) to compare their providers (physicians and APPs) and associated outcomes. MATERIALS AND METHODS: We identified all e-visits for the UPMC AnywhereCare Continuity (physician providers for existing patients) and Convenience (physician and APP providers for Pennsylvania residents) services (n=2,184) using Epic Systems (Verona, WI) MyChart data (November 2013-August 2014). We compared e visits by service and provider type for patient characteristics, volume, response time, primary diagnoses, and number of prescriptions. We used statistical tests to determine differences in patient characteristics and an ordinary least square linear regression, controlling for patient characteristics, to determine differences in prescribing. RESULTS: Of the completed e-visits (n=1,791), 72.5% were with APPs, and 27.5% were with physicians. APP patients were younger, higher income, and more likely to be unmarried. Sinusitis patients were more likely to use the Continuity service, whereas those with urinary tract or upper respiratory infections were more likely to use the Convenience service. Finally, provider type was significantly associated with prescribing, with APPs prescribing more. CONCLUSIONS: Some demographic variation exists between users of APP versus physician e-visits. Provider response time seems more driven by service policy than provider type. Finally, variation exists between provider types in quantities of prescriptions written. As health systems and policymakers develop protocols and reimbursement strategies for e-visits, these model considerations will be important. PMID- 26161624 TI - Epilepsy: behavioural, psychological, and ketogenic diet treatments. AB - INTRODUCTION: About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of behavioural and psychological treatments in people with epilepsy? What are the effects of ketogenic diets in people with epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version). RESULTS: Searching of electronic databases retrieved 259 studies. After deduplication and removal of conference abstracts, 253 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 208 studies and the further review of 45 full publications. Of the 45 full articles evaluated, six systematic reviews and seven RCTs were included at this update. We performed a GRADE evaluation for six PICO combinations. CONCLUSIONS: In this systematic overview we categorised the efficacy for seven interventions, based on information relating to the effectiveness and safety of: biofeedback, cognitive behavioural therapy (CBT), educational programmes, family counselling, ketogenic diet, relaxation therapy (alone or plus behavioural modification therapy), and yoga. PMID- 26161625 TI - Ultrasound Imaging in Postpartum Women With Diastasis Recti: Intrarater Between Session Reliability. AB - STUDY DESIGN: Clinimetrics. OBJECTIVES: To investigate the intrarater between session reliability of inter-rectus distance (IRD) measurement using ultrasound imaging in postpartum women with diastasis recti. BACKGROUND: Diastasis recti, a separation of the rectus abdominis muscles at the linea alba, occurs as a result of pregnancy and is characterized by increased IRD. The measurement of IRD in this population is of interest to determine changes in diastasis recti severity over time, or in response to treatment. Ultrasound imaging has been proposed as a useful tool to measure IRD in women with diastasis recti; however, the consistency of IRD measurement in this population using ultrasound imaging has, to our knowledge, never been investigated. METHODS: Ultrasound imaging was used to measure IRD in 20 women with diastasis recti on 2 different occasions. On each testing occasion, images were acquired at 4 locations along the linea alba while participants remained relaxed and while they performed a head lift to activate the rectus abdominis muscles. Reliability statistics included intraclass correlation coefficients, Bland-Altman analyses, minimum clinically important difference, and standard error of the measurement. RESULTS: Between-session reliability of IRD measurement was high, particularly when measuring IRD at or above the umbilicus, as indicated by intraclass correlation coefficients greater than 0.90 and low standard error of the measurement and minimum clinically important difference values (below 0.17 cm and 0.46 cm, respectively). Reliability coefficients were poorer when measuring IRD below the umbilicus. CONCLUSION: When performed by an experienced investigator, ultrasound imaging is a reliable tool by which to measure IRD in postpartum women who have diastasis recti. PMID- 26161627 TI - Manual Physical Therapy Following Immobilization for Stable Ankle Fracture: A Case Series. AB - STUDY DESIGN: Case series. BACKGROUND: Ankle fractures commonly result in persistent pain, stiffness, and functional impairments. There is insufficient evidence to favor any particular rehabilitation approach after ankle fracture. The purpose of this case series was to describe an impairment-based manual physical therapy approach to treating patients with conservatively managed ankle fractures. CASE DESCRIPTION: Patients with stable ankle fractures postimmobilization were treated with manual physical therapy and exercise targeted at associated impairments in the lower limb. The primary outcome measure was the Lower Extremity Functional Scale. Secondary outcome measures included the ankle lunge test, numeric pain-rating scale, and global rating of change. Outcome measures were collected at baseline (performed within 7 days of immobilization removal) and at 4 and 12 weeks postbaseline. OUTCOMES: Eleven patients (mean age, 39.6 years; range, 18-64 years; 2 male), after ankle fracture-related immobilization (mean duration, 48 days; range, 21-75 days), were treated for an average of 6.6 sessions (range, 3-10 sessions) over a mean of 46.1 days (range, 13-81 days). Compared to baseline, statistically significant and clinically meaningful improvements were observed in Lower Extremity Functional Scale score (P = .001; mean change, 21.9 points; 95% confidence interval: 10.4, 33.4) and in the ankle lunge test (P = .001; mean change, 7.8 cm; 95% confidence interval: 3.9, 11.7) at 4 weeks. These changes persisted at 12 weeks. DISCUSSION: Statistically significant and clinically meaningful improvements in self-reported function and ankle range of motion were observed at 4 and 12 weeks following treatment with impairment-based manual physical therapy. All patients tolerated treatment well. Results suggest that this approach may have efficacy in this population. LEVEL OF EVIDENCE: Therapy, level 4. PMID- 26161626 TI - Higher Knee Flexion Moment During the Second Half of the Stance Phase of Gait Is Associated With the Progression of Osteoarthritis of the Patellofemoral Joint on Magnetic Resonance Imaging. AB - STUDY DESIGN: Controlled laboratory study, longitudinal design. OBJECTIVE: To examine whether baseline knee flexion moment or impulse during walking is associated with the progression of osteoarthritis (OA) with magnetic resonance imaging of the patellofemoral joint (PFJ) at 1 year. BACKGROUND: Patellofemoral joint OA is highly prevalent and a major source of pain and dysfunction. The biomechanical factors associated with the progression of PFJ OA remain unclear. METHODS: Three-dimensional gait analyses were performed at baseline. Magnetic resonance imaging of the knee (high-resolution, 3-D, fast spin-echo sequence) was used to identify PFJ cartilage and bone marrow edema-like lesions at baseline and a 1-year follow-up. The severity of PFJ OA progression was defined using the modified Whole-Organ Magnetic Resonance Imaging Score when new or increased cartilage or bone marrow edema-like lesions were observed at 1 year. Peak external knee flexion moment and flexion moment impulse during the first and second halves of the stance phase of gait were compared between progressors and nonprogressors, and used to predict progression after adjusting for age, sex, body mass index, and presence of baseline PFJ OA. RESULTS: Sixty-one participants with no knee OA or isolated PFJ OA were included. Patellofemoral joint OA progressors (n = 10) demonstrated significantly higher peak knee flexion moment (P = .01) and flexion moment impulse (P = .04) during the second half of stance at baseline compared to nonprogressors. Logistic regression showed that higher peak knee flexion moment during the second half of the stance phase was significantly associated with progression at 1 year (adjusted odds ratio = 3.3, P = .01). CONCLUSION: Peak knee flexion moment and flexion moment impulse during the second half of stance are related to the progression of PFJ OA and may need to be considered when treating individuals who are at risk of or who have PFJ OA. PMID- 26161628 TI - Detecting Meniscal Tears in Primary Care: Reproducibility and Accuracy of 2 Weight-Bearing Tests and 1 Non-Weight-Bearing Test. AB - STUDY DESIGN: Diagnostic accuracy study using a cross-sectional design. OBJECTIVES: To determine the interexaminer reliability and the diagnostic accuracy in primary care of 1 existing weight-bearing meniscal test, the Thessaly test, 1 new weight-bearing test, the deep squat test, and 1 non-weight-bearing test, the joint-line tenderness test. BACKGROUND: Meniscal tears are difficult to detect in primary care. Although valuable in secondary care, weight-bearing physical examination tests require validation in primary care in unselected patients. METHODS: Between October 2009 and December 2013, 121 patients (age range, 18-65 years) seen in primary care and suspected of having internal derangement of the knee of less than 6 months in duration were included in the study. Diagnostic accuracy of the 3 meniscal tests was determined based on assessment with magnetic resonance imaging. The meniscal tests were performed by 3 trained physical therapists, who were not informed about the patient history and magnetic resonance imaging results. Each test was performed independently by 2 of the 3 trained physical therapists in alternating pairs. RESULTS: The Thessaly test and the deep squat test had a moderate level of interexaminer reliability, with kappas of 0.54 and 0.46, respectively. The joint-line tenderness test had poor interexaminer reliability and was therefore not assessed for diagnostic accuracy. The following results are reported separately for both examiners. The Thessaly test had a sensitivity of 66.7% (95% confidence interval [CI]: 53.0%, 78.0%) and 51.2% (95% CI: 36.8%, 65.4%), a specificity of 37.9% (95% CI: 27.2%, 50.0%) and 43.5% (95% CI: 30.2%, 57.8%), a positive likelihood ratio of 1.07 (95% CI: 0.82, 1.41) and 0.91 (95% CI: 0.62, 1.33), and a negative likelihood ratio of 0.88 (95% CI: 0.54, 1.45) and 1.12 (95% CI: 0.72, 1.76). Similarly, the deep squat test had a sensitivity of 74.5% (95% CI: 61.1%, 84.5%) and 76.7% (95% CI: 62.3%, 86.9%), a specificity of 42.4% (95% CI: 31.2%, 54.4%) and 36.2% (95% CI: 24.0%, 50.5%), a positive likelihood ratio of 1.29 (95% CI: 0.97, 1.68) and 1.20 (95% CI: 0.92, 1.58), and a negative likelihood ratio of 0.60 (95% CI: 0.35, 1.04) and 0.64 (95% CI: 0.33, 1.25). CONCLUSION: Although the Thessaly and deep squat tests have a moderate level of reliability, neither test is sufficiently accurate to help in the diagnosis of meniscal tears in primary care. Future research should focus on other relevant patient variables instead of on physical examination tests in the detection of meniscal tears. LEVEL OF EVIDENCE: Diagnosis, level 3b. PMID- 26161629 TI - Resisted Side Stepping: The Effect of Posture on Hip Abductor Muscle Activation. AB - STUDY DESIGN: Controlled laboratory study, repeated-measures design. OBJECTIVES: To compare hip abductor muscle activity and hip and knee joint kinematics in the moving limb to the stance limb during resisted side stepping, and to determine whether muscle activity was affected by the posture (upright standing versus squat) used to perform the exercise. BACKGROUND: Hip abductor weakness has been associated with a variety of lower extremity injuries. Resisted side stepping is often used as an exercise to increase strength and endurance of the hip abductors. Exercise prescription would benefit from knowing the relative muscle activity level generated in each limb and for different postures during the side stepping exercise. METHODS: Twenty-four healthy adults participated in this study. Kinematics and surface electromyographic data from the gluteus maximus, gluteus medius, and tensor fascia lata were collected as participants performed side stepping with a resistive band around the ankle, while maintaining each of 2 postures: (1) upright standing and (2) squat. RESULTS: Mean normalized electromyographic signal amplitude of the gluteus maximus, gluteus medius, and tensor fascia lata was higher in the stance limb than in the moving limb (P<=.001). Gluteal muscle activity was higher, whereas tensor fascia lata muscle activity was lower, in the squat posture compared to the upright standing posture (P<.001). Hip abduction excursion was greater in the stance limb than in the moving limb (P<.001). CONCLUSION: The 3 hip abductor muscles respond differently to the posture variations of the side-stepping exercise in healthy individuals. When prescribing resisted side-stepping exercises, therapists should consider the differences in hip abductor activation across limbs and variations in trunk posture. PMID- 26161630 TI - Dictionary learning for data recovery in positron emission tomography. AB - Compressed sensing (CS) aims to recover images from fewer measurements than that governed by the Nyquist sampling theorem. Most CS methods use analytical predefined sparsifying domains such as total variation, wavelets, curvelets, and finite transforms to perform this task. In this study, we evaluated the use of dictionary learning (DL) as a sparsifying domain to reconstruct PET images from partially sampled data, and compared the results to the partially and fully sampled image (baseline).A CS model based on learning an adaptive dictionary over image patches was developed to recover missing observations in PET data acquisition. The recovery was done iteratively in two steps: a dictionary learning step and an image reconstruction step. Two experiments were performed to evaluate the proposed CS recovery algorithm: an IEC phantom study and five patient studies. In each case, 11% of the detectors of a GE PET/CT system were removed and the acquired sinogram data were recovered using the proposed DL algorithm. The recovered images (DL) as well as the partially sampled images (with detector gaps) for both experiments were then compared to the baseline. Comparisons were done by calculating RMSE, contrast recovery and SNR in ROIs drawn in the background, and spheres of the phantom as well as patient lesions.For the phantom experiment, the RMSE for the DL recovered images were 5.8% when compared with the baseline images while it was 17.5% for the partially sampled images. In the patients' studies, RMSE for the DL recovered images were 3.8%, while it was 11.3% for the partially sampled images. Our proposed CS with DL is a good approach to recover partially sampled PET data. This approach has implications toward reducing scanner cost while maintaining accurate PET image quantification. PMID- 26161632 TI - Using high-fidelity virtual reality to study perception in freely moving observers. AB - Technological innovations have had a profound influence on how we study the sensory perception in humans and other animals. One example was the introduction of affordable computers, which radically changed the nature of visual experiments. It is clear that vision research is now at cusp of a similar shift, this time driven by the use of commercially available, low-cost, high-fidelity virtual reality (VR). In this review we will focus on: (a) the research questions VR allows experimenters to address and why these research questions are important, (b) the things that need to be considered when using VR to study human perception, PMID- 26161631 TI - Using 10AFC to further improve the efficiency of the quick CSF method. AB - The contrast sensitivity function (CSF) provides a fundamental characterization of spatial vision, important for basic and clinical applications, but its long testing times have prevented easy, widespread assessment. The original quick CSF method was developed using a two-alternative forced choice (2AFC) grating orientation identification task (Lesmes, Lu, Baek, & Albright, 2010), and obtained precise CSF assessments while reducing the testing burden to only 50 trials. In this study, we attempt to further improve the efficiency of the quick CSF method by exploiting the properties of psychometric functions in multiple alternative forced choice (m-AFC) tasks. A simulation study evaluated the effect of the number of alternatives m on the efficiency of the sensitivity measurement by the quick CSF method, and a psychophysical study validated the quick CS method in a 10AFC task. We found that increasing the number of alternatives of the forced-choice task greatly improved the efficiency of CSF assessment in both simulation and psychophysical studies. The quick CSF method based on a 10-letter identification task can assess the CSF with an averaged standard deviation of 0.10 decimal log unit in less than 2 minutes. PMID- 26161633 TI - An object-centered aftereffect of a latent material property: A squishiness visual aftereffect, not causality adaptation. AB - Visual aftereffects are characterized by a changed perceptual experience after exposure to a visual input. For instance, exposure to rightward motion can make a static input seem to drift leftward-the motion aftereffect. Such aftereffects have been integral to building our understanding of the neural mechanisms and computational processes that underlie perception. Increasingly complex characteristics have been found to be susceptible to visual aftereffects, such as the appearance of human faces, the apparent number of visual elements, and the glossiness of a surface. Here we report that the apparent elasticity, or squishiness, of an object is also subject to a visual aftereffect. This relationship can explain data previously interpreted in terms of a causality aftereffect. PMID- 26161634 TI - Probing the Role of N-Acetyl-glutamyl 5-Phosphate, an Acyl Phosphate, in the Construction of the Azabicycle Moiety of the Azinomycins. AB - The azinomycins are potent antitumor agents produced by the soil bacterium Streptomyces sahachiroi and contain a novel aziridino[1,2-a]pyrrolidine core; its synthesis involves at least 14 steps. This study reports the first reconstitution of N-acetylglutamine semialdehyde formation by two enzymes encoded in the azinomycin biosynthetic gene cluster. The reaction proceeds through the formation of an acylphosphate and establishes N-acetyl-glutamyl 5-phosphate and N acetylglutamine semialdehyde as intermediates in the complex biosynthesis of the aziridino[1,2-a]pyrrolidine moiety. PMID- 26161635 TI - Rhizobium-legume symbiosis in the absence of Nod factors: two possible scenarios with or without the T3SS. AB - The occurrence of alternative Nod factor (NF)-independent symbiosis between legumes and rhizobia was first demonstrated in some Aeschynomene species that are nodulated by photosynthetic bradyrhizobia lacking the canonical nodABC genes. In this study, we revealed that a large diversity of non-photosynthetic bradyrhizobia, including B. elkanii, was also able to induce nodules on the NF independent Aeschynomene species, A. indica. Using cytological analysis of the nodules and the nitrogenase enzyme activity as markers, a gradient in the symbiotic interaction between bradyrhizobial strains and A. indica could be distinguished. This ranged from strains that induced nodules that were only infected intercellularly to rhizobial strains that formed nodules in which the host cells were invaded intracellularly and that displayed a weak nitrogenase activity. In all non-photosynthetic bradyrhizobia, the type III secretion system (T3SS) appears required to trigger nodule organogenesis. In contrast, genome sequence analysis revealed that apart from a few exceptions, like the Bradyrhizobium ORS285 strain, photosynthetic bradyrhizobia strains lack a T3SS. Furthermore, analysis of the symbiotic properties of an ORS285 T3SS mutant revealed that the T3SS could have a positive or negative role for the interaction with NF-dependent Aeschynomene species, but that it is dispensable for the interaction with all NF-independent Aeschynomene species tested. Taken together, these data indicate that two NF-independent symbiotic processes are possible between legumes and rhizobia: one dependent on a T3SS and one using a so far unknown mechanism. PMID- 26161637 TI - Reversible Halide Exchange Reaction of Organometal Trihalide Perovskite Colloidal Nanocrystals for Full-Range Band Gap Tuning. AB - In recent years, methylammonium lead halide (MAPbX3, where X = Cl, Br, and I) perovskites have attracted tremendous interest caused by their outstanding photovoltaic performance. Mixed halides have been frequently used as the active layer of solar cells, as a result of their superior physical properties as compared to those of traditionally used pure iodide. Herein, we report a remarkable finding of reversible halide-exchange reactions of MAPbX3, which facilitates the synthesis of a series of mixed halide perovskites. We synthesized MAPbBr3 plate-type nanocrystals (NCs) as a starting material by a novel solution reaction using octylamine as the capping ligand. The synthesis of MAPbBr(3-x)Clx and MAPbBr(3-x)Ix NCs was achieved by the halide exchange reaction of MAPbBr3 with MACl and MAI, respectively, in an isopropyl alcohol solution, demonstrating full-range band gap tuning over a wide range (1.6-3 eV). Moreover, photodetectors were fabricated using these composition-tuned NCs; a strong correlation was observed between the photocurrent and photoluminescence decay time. Among the two mixed halide perovskite series, those with I-rich composition (x = 2), where a sole tetragonal phase exists without the incorporation of a cubic phase, exhibited the highest photoconversion efficiency. To understand the composition dependent photoconversion efficiency, first-principles density-functional theory calculations were carried out, which predicted many plausible configurations for cubic and tetragonal phase mixed halides. PMID- 26161638 TI - Enantioselective Synthesis of Chromanones Bearing Quaternary Substituted Stereocenters Catalyzed by (1R)-Camphor-Derived N-Heterocyclic Carbenes. AB - A catalytic asymmetric intramolecular crossed-benzoin reaction for the synthesis of chromanones by novel camphor-derived N-heterocyclic carbenes is described. The corresponding chromanones bearing quaternary stereogenic centers were isolated in high yields with high to excellent enantioselectivity. PMID- 26161636 TI - Microbial catabolic activities are naturally selected by metabolic energy harvest rate. AB - The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate. PMID- 26161639 TI - Improved Prediction of Preterm Delivery Using Empirical Mode Decomposition Analysis of Uterine Electromyography Signals. AB - Preterm delivery increases the risk of infant mortality and morbidity, and therefore developing reliable methods for predicting its likelihood are of great importance. Previous work using uterine electromyography (EMG) recordings has shown that they may provide a promising and objective way for predicting risk of preterm delivery. However, to date attempts at utilizing computational approaches to achieve sufficient predictive confidence, in terms of area under the curve (AUC) values, have not achieved the high discrimination accuracy that a clinical application requires. In our study, we propose a new analytical approach for assessing the risk of preterm delivery using EMG recordings which firstly employs Empirical Mode Decomposition (EMD) to obtain their Intrinsic Mode Functions (IMF). Next, the entropy values of both instantaneous amplitude and instantaneous frequency of the first ten IMF components are computed in order to derive ratios of these two distinct components as features. Discrimination accuracy of this approach compared to those proposed previously was then calculated using six differently representative classifiers. Finally, three different electrode positions were analyzed for their prediction accuracy of preterm delivery in order to establish which uterine EMG recording location was optimal signal data. Overall, our results show a clear improvement in prediction accuracy of preterm delivery risk compared with previous approaches, achieving an impressive maximum AUC value of 0.986 when using signals from an electrode positioned below the navel. In sum, this provides a promising new method for analyzing uterine EMG signals to permit accurate clinical assessment of preterm delivery risk. PMID- 26161640 TI - A Simulation Model for Intra-Urban Movements. AB - Human mobility patterns (HMP) have become of interest to a variety of disciplines. The increasing availability of empirical data enables researchers to analyze patterns of people's movements. Recent work suggested that HMP follow a Levy-flight distribution and present regularity. Here, we present an innovative agent-based model that simulates HMP for various purposes. It is based on the combination of regular movements with spatial considerations, represented by an expanded gravitation model. The agents in this model have different attributes that affect their choice of destination and the duration they stay in each location. Thus, their movement mimics real-life situations. This is a stochastic, bottom-up model, yet it yields HMP that qualitatively fit HMP empirical data in terms of individuals, as well as the entire population. Our results also correspond to real-life phenomena in terms of urban spatial dynamics, that is, the emergence of popular locations in the city due to bottom-up behavior of people. Our model is novel in being based on the assumption that HMP are space dependent as well as follow high regularity. To our knowledge, we are the first to succeed in simulating HMP not only at the inter-city scale but also at the intra-urban one. PMID- 26161642 TI - ParAB Partition Dynamics in Firmicutes: Nucleoid Bound ParA Captures and Tethers ParB-Plasmid Complexes. AB - In Firmicutes, small homodimeric ParA-like (delta2) and ParB-like (omega2) proteins, in concert with cis-acting plasmid-borne parS and the host chromosome, secure stable plasmid inheritance in a growing bacterial population. This study shows that (omega:YFP)2 binding to parS facilitates plasmid clustering in the cytosol. (delta:GFP)2 requires ATP binding but not hydrolysis to localize onto the cell's nucleoid as a fluorescent cloud. The interaction of (delta:CFP)2 or delta2 bound to the nucleoid with (omega:YFP)2 foci facilitates plasmid capture, from a very broad distribution, towards the nucleoid and plasmid pairing. parS bound omega2 promotes redistribution of (delta:GFP)2, leading to the dynamic release of (delta:GFP)2 from the nucleoid, in a process favored by ATP hydrolysis and protein-protein interaction. (deltaD60A:GFP)2, which binds but cannot hydrolyze ATP, also forms unstable complexes on the nucleoid. In the presence of omega2, (deltaD60A:GFP)2 accumulates foci or patched structures on the nucleoid. We propose that (delta:GFP)2 binding to different nucleoid regions and to omega2 parS might generate (delta:GFP)2 gradients that could direct plasmid movement. The iterative pairing and unpairing cycles may tether plasmids equidistantly on the nucleoid to ensure faithful plasmid segregation by a mechanism compatible with the diffusion-ratchet mechanism as proposed from in vitro reconstituted systems. PMID- 26161641 TI - Unraveling the Rat Intestine, Spleen and Liver Genome-Wide Transcriptome after the Oral Administration of Lavender Oil by a Two-Color Dye-Swap DNA Microarray Approach. AB - The use of lavender oil (LO)--a commonly, used oil in aromatherapy, with well defined volatile components linalool and linalyl acetate--in non-traditional medicine is increasing globally. To understand and demonstrate the potential positive effects of LO on the body, we have established an animal model in this current study, investigating the orally administered LO effects genome wide in the rat small intestine, spleen, and liver. The rats were administered LO at 5 mg/kg (usual therapeutic dose in humans) followed by the screening of differentially expressed genes in the tissues, using a 4*44-K whole-genome rat chip (Agilent microarray platform; Agilent Technologies, Palo Alto, CA, USA) in conjunction with a dye-swap approach, a novelty of this study. Fourteen days after LO treatment and compared with a control group (sham), a total of 156 and 154 up (? 1.5-fold)- and down (? 0.75-fold)-regulated genes, 174 and 66 up- (? 1.5-fold)- and down (? 0.75-fold)-regulated genes, and 222 and 322 up- (? 1.5 fold)- and down (? 0.75-fold)-regulated genes showed differential expression at the mRNA level in the small intestine, spleen and liver, respectively. The reverse transcription-polymerase chain reaction (RT-PCR) validation of highly up- and down-regulated genes confirmed the regulation of the Papd4, Lrp1b, Alb, Cyr61, Cyp2c, and Cxcl1 genes by LO as examples in these tissues. Using bioinformatics, including Ingenuity Pathway Analysis (IPA), differentially expressed genes were functionally categorized by their Gene Ontology (GO) and biological function and network analysis, revealing their diverse functions and potential roles in LO-mediated effects in rat. Further IPA analysis in particular unraveled the presence of novel genes, such as Papd4, Or8k5, Gprc5b, Taar5, Trpc6, Pld2 and Onecut3 (up-regulated top molecules) and Tnf, Slc45a4, Slc25a23 and Samt4 (down-regulated top molecules), to be influenced by LO treatment in the small intestine, spleen and liver, respectively. These results are the first such inventory of genes that are affected by lavender essential oil (LO) in an animal model, forming the basis for further in-depth bioinformatics and functional analyses and investigation. PMID- 26161643 TI - Structural Insight into and Mutational Analysis of Family 11 Xylanases: Implications for Mechanisms of Higher pH Catalytic Adaptation. AB - To understand the molecular basis of higher pH catalytic adaptation of family 11 xylanases, we compared the structures of alkaline, neutral, and acidic active xylanases and analyzed mutants of xylanase Xyn11A-LC from alkalophilic Bacillus sp. SN5. It was revealed that alkaline active xylanases have increased charged residue content, an increased ratio of negatively to positively charged residues, and decreased Ser, Thr, and Tyr residue content relative to non-alkaline active counterparts. Between strands beta6 and beta7, alkaline xylanases substitute an alpha-helix for a coil or turn found in their non-alkaline counterparts. Compared with non-alkaline xylanases, alkaline active enzymes have an inserted stretch of seven amino acids rich in charged residues, which may be beneficial for xylanase function in alkaline conditions. Positively charged residues on the molecular surface and ionic bonds may play important roles in higher pH catalytic adaptation of family 11 xylanases. By structure comparison, sequence alignment and mutational analysis, six amino acids (Glu16, Trp18, Asn44, Leu46, Arg48, and Ser187, numbering based on Xyn11A-LC) adjacent to the acid/base catalyst were found to be responsible for xylanase function in higher pH conditions. Our results will contribute to understanding the molecular mechanisms of higher pH catalytic adaptation in family 11 xylanases and engineering xylanases to suit industrial applications. PMID- 26161644 TI - Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine? AB - BACKGROUND: Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes. METHODOLOGY/PRINCIPAL FINDINGS: We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function. CONCLUSIONS/SIGNIFICANCE: Our data suggest that rhesus macaques self cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets. PMID- 26161645 TI - What Directions Do We Look at Power from? Up-Down, Left-Right, and Front-Back. AB - Three experiments were carried out to investigate whether the the kinship concept had spatial representations along up-down (Experiment 1), left-right (Experiment 2), and front-back (Experiment 3) orientation. Participants identified the letter P or Q after judging whether kinship words were elder or junior terms. The results showed that participants responded faster to letters placed at the top, right side, and front following elder terms, and faster at the bottom, left side, and back following junior terms. The regression results further confirmed that these shifts of attention along up-down, right-left, and front-back dimensions in external space were uniquely attributed to the power construct embedded in the kinship concept, but not number or time. The results provide evidence for the multiple spatial representations in power, and can be explained by the theoretical construct of structural mapping. PMID- 26161646 TI - Whole-Genome Sequencing Analysis of Sapovirus Detected in South Korea. AB - Sapovirus (SaV), a virus residing in the intestines, is one of the important causes of gastroenteritis in human beings. Human SaV genomes are classified into various genogroups and genotypes. Whole-genome analysis and phylogenetic analysis of ROK62, the SaV isolated in South Korea, were carried out. The ROK62 genome of 7429 nucleotides contains 3 open-reading frames (ORF). The genotype of ROK62 is SaV GI-1, and 94% of its nucleotide sequence is identical with other SaVs, namely Manchester and Mc114. Recently, SaV infection has been on the rise throughout the world, particularly in countries neighboring South Korea; however, very few academic studies have been done nationally. As the first whole-genome sequence analysis of SaV in South Korea, this research will help provide reference for the detection of recombination, tracking of epidemic spread, and development of diagnosis methods for SaV. PMID- 26161647 TI - Toll-Like Receptor 4 Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk. AB - Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion. PMID- 26161648 TI - Investigating the Goldilocks Hypothesis: The Non-Linear Impact of Positive Trait Change on Well-Being. AB - This paper attempts to reconcile two perspectives on the impact of positive trait change. The first perspective views positive trait change as salubrious because it reflects the process of self-enhancement, whereas the second perspective views positive change as costly because it disrupts the self-verification process. We propose that benefits and costs accrue at discrete rates, such that moderate positive trait change is more beneficial than too little and too much positive change. This constitutes a Goldilocks hypothesis. Using the MIDUS longitudinal dataset (N = 1,725) we test this hypothesis on four traits, namely, social extraversion, agentic extraversion (agency), conscientiousness, and neuroticism. The Goldilocks hypothesis was supported for social extraversion, agentic extraversion (agency), and conscientiousness. Reduction in neuroticism seemed uniformly predictive of higher well-being. Thus, not all amounts of positive trait change are beneficial. While we find no evidence for a limit to the benefits of reduced neuroticism, there is a "just right" amount of positive change in extraversion and conscientiousness that results in the highest level of well-being. Our findings suggest that non-monotonic models may be more valid in investigations of personality change and well-being. PMID- 26161650 TI - Local Variation of Hashtag Spike Trains and Popularity in Twitter. AB - We draw a parallel between hashtag time series and neuron spike trains. In each case, the process presents complex dynamic patterns including temporal correlations, burstiness, and all other types of nonstationarity. We propose the adoption of the so-called local variation in order to uncover salient dynamical properties, while properly detrending for the time-dependent features of a signal. The methodology is tested on both real and randomized hashtag spike trains, and identifies that popular hashtags present regular and so less bursty behavior, suggesting its potential use for predicting online popularity in social media. PMID- 26161649 TI - Fibulin-1C, C1 Esterase Inhibitor and Glucose Regulated Protein 75 Interact with the CREC Proteins, Calumenin and Reticulocalbin. AB - Affinity purification, immunoprecipitation, gel electrophoresis and mass spectrometry were used to identify fibulin-1C, C1 esterase inhibitor and glucose regulated protein 75, grp75, as binding partners of the CREC proteins, calumenin and reticulocalbin. Surface plasmon resonance was used to verify the interaction of all three proteins with each of the CREC proteins. Fibulin-1C interacts with calumenin and reticulocalbin with an estimated dissociation constant around 50-60 nM. The interaction, at least for reticulocalbin, was not dependent upon the presence of Ca2+. C1 esterase inhibitor interacted with both proteins with an estimated dissociation constant at 1 MUM for reticulocalbin and 150 nM for calumenin. The interaction, at least for calumenin, was dependent upon the presence of Ca2+ with strong interaction at 3.5 mM while no detectable interaction could be found at 0.1 mM. Grp75 binds with an affinity of approximately 3-7 nM with reticulocalbin as well as with calumenin. These interactions suggest functional participation of the CREC proteins in chaperone activity, cell proliferation and transformation, cellular aging, haemostasis and thrombosis as well as modulation of the complement system in fighting bacterial infection. PMID- 26161651 TI - Spatial Clustering Properties in the Temporal Variation of Suicide Rates/Numbers among Japanese Citizens: A Comprehensive Comparison and Discussion. AB - OBJECTIVE: The number of suicides in Japan has remained high for many years. To effectively resolve this problem, firm understanding of the statistical data is required. Using a large quantity of wide-ranging data on Japanese citizens, the purpose of this study was to analyze the geographical clustering properties of suicides and how suicide rates have evolved over time, and to observe detailed patterns and trends in a variety of geographic regions. METHODS: Using adjacency data from 2008, the spatial and temporal/spatial clustering structure of geographic statistics on suicides were clarified. Echelon scans were performed to identify regions with the highest-likelihood ratio of suicide as the most likely suicide clusters. RESULTS: In contrast to results obtained using temporal/spatial analysis, the results of a period-by-period breakdown of evolving suicide rates demonstrated that suicides among men increased particularly rapidly during 1988 1992, 1993-1997, and 1998-2002 in certain cluster regions located near major metropolitan areas. For women, results identified cluster regions near major metropolitan areas in 1993-1997, 1998-2002, and 2003-2007. CONCLUSIONS: For both men and women, the cluster regions identified are located primarily near major metropolitan areas, such as greater Tokyo and Osaka. PMID- 26161652 TI - Prioritizing Wetlands for Waterbirds in a Boom and Bust System: Waterbird Refugia and Breeding in the Murray-Darling Basin. AB - Dryland rivers have considerable flow variability, producing complex ecosystems, processes, and communities of organisms that vary over space and time. They are also among the more vulnerable of the world's ecosystems. A key strategy for conservation of dryland rivers is identifying and maintaining key sites for biodiversity conservation, particularly protecting the quantity and quality of flow and flooding regimes. Extreme variability considerably challenges freshwater conservation planning. We systematically prioritised wetlands for waterbirds (simultaneously for 52 species), across about 13.5% of the Murray-Darling Basin (1,061,469 km2), using a 30-year record of systematic aerial surveys of waterbird populations. Nine key wetlands in this area, primarily lakes, floodplains, and swamps, consistently contributed to a representation target (80%) of total abundances of all 52 waterbird species. The long temporal span of our data included dramatic availability (i.e., booms) and scarcity (i.e., busts) of water, providing a unique opportunity to test prioritisation at extremes of variation. These extremes represented periods when waterbirds were breeding or concentrating on refugia, varying wetland prioritisation. In dry years, important wetlands for waterbirds were riverine and lacustrine (12 wetlands) but this changed in wet years to lacustrine and palustrine (8 wetlands). Such variation in ecosystem condition substantially changes the relative importance of individual wetlands for waterbirds during boom and bust phases. Incorporating this variability is necessary for effective conservation of Murray-Darling Basin waterbirds, with considerable generality for other similarly variable systems around the world. PMID- 26161653 TI - PEDro or Cochrane to Assess the Quality of Clinical Trials? A Meta Epidemiological Study. AB - OBJECTIVE: There is debate on how the methodological quality of clinical trials should be assessed. We compared trials of physical therapy (PT) judged to be of adequate quality based on summary scores from the Physiotherapy Evidence Database (PEDro) scale with trials judged to be of adequate quality by Cochrane Risk of Bias criteria. DESIGN: Meta-epidemiological study within Cochrane Database of Systematic Reviews. METHODS: Meta-analyses of PT trials were identified in the Cochrane Database of Systematic Reviews. For each trial PeDro and Cochrane assessments were extracted from the PeDro and Cochrane databases. Adequate quality was defined as adequate generation of random sequence, concealment of allocation, and blinding of outcome assessors (Cochrane criteria) or as trials with a PEDro summary score >=5 or >=6 points. We combined trials of adequate quality using random-effects meta-analysis. RESULTS: Forty-one Cochrane reviews and 353 PT trials were included. All meta-analyses included trials with PEDro scores >=5, 37 (90.2%) included trials with PEDro scores >=6 and only 22 (53.7%) meta-analyses included trials of adequate quality according to the Cochrane criteria. Agreement between PeDro and Cochrane was poor for PeDro scores of >=5 points (kappa = 0.12; 95% CI 0.07 to 0.16) and slight for >=6 points (kappa 0.24; 95% CI 0.16-0.32). When combining effect sizes of trials deemed to be of adequate quality according to PEDro or Cochrane criteria, we found that a substantial difference in the combined effect size (>=0.15) was evident in 9 (22%) out of the 41 meta-analyses for PEDro cutoff >=5 and 10 (24%) for cutoff >=6. CONCLUSIONS: The PeDro and Cochrane approaches lead to different sets of trials of adequate quality, and different combined treatment estimates from meta-analyses of these trials. A consistent approach to assessing RoB in trials of physical therapy should be adopted. PMID- 26161654 TI - A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs. AB - Methionine is a rate-limiting amino-acid for protein synthesis but non proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight) were restrictively-fed diets providing either an adequate (CTRL) or a deficient methionine supply (MD) during 10 days (n=6 per group). At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently adapts tissue metabolisms when facing an insufficient methionine supply. PMID- 26161655 TI - Clinical Ethics in Gabon: The Spectrum of Clinical Ethical Issues Based on Findings from In-Depth Interviews at Three Public Hospitals. AB - INTRODUCTION: Unlike issues in biomedical research ethics, ethical challenges arising in daily clinical care in Sub-Saharan African countries have not yet been studied in a systematic manner. However this has to be seen as a distinct entity as we argue in this paper. Our aim was to give an overview of the spectrum of clinical ethical issues and to understand what influences clinical ethics in the Sub-Saharan country of Gabon. MATERIALS AND METHODS: In-depth interviews with 18 health care professionals were conducted at three hospital sites in Gabon. Interview transcripts were analyzed using a grounded theory approach (open and axial coding), giving a qualitative spectrum of categories for clinical ethical issues. Validity was checked at a meeting with study participants and other health care experts in Gabon after analysis of the data. RESULTS: Twelve main categories (with 28 further-specified subcategories) for clinical ethical issues were identified and grouped under three core categories: A) micro level: "confidentiality and information", "interpersonal, relational and behavioral issues", "psychological strain of individuals", and "scarce resources"; B) meso level: "structural issues of medical institutions", "issues with private clinics", "challenges connected to the family", and "issues of education, training and competence"; and C) macro level: "influence of society, culture, religion and superstition", "applicability of western medicine", "structural issues on the political level", and "legal issues". DISCUSSION: Interviewees reported a broad spectrum of clinical ethical issues that go beyond challenges related to scarce financial and human resources. Specific socio-cultural, historical and educational backgrounds also played an important role. In fact these influences are central to an understanding of clinical ethics in the studied local context. Further research in the region is necessary to put our study into perspective. As many participants reported a lack of awareness of ethical issues amongst other health care professionals in daily clinical practice, we suggest that international organizations and national medical schools should consider infrastructure and tools to improve context-sensitive capacity building in clinical ethics for Sub-Saharan African countries like Gabon. PMID- 26161656 TI - Inclusive Composite Interval Mapping of QTL by Environment Interactions in Biparental Populations. AB - Identification of environment-specific QTL and stable QTL having consistent genetic effects across a wide range of environments is of great importance in plant breeding. Inclusive Composite Interval Mapping (ICIM) has been proposed for additive, dominant and epistatic QTL mapping in biparental populations for single environment. In this study, ICIM was extended to QTL by environment interaction (QEI) mapping for multi-environmental trials, where the QTL average effect and QEI effects could be properly estimated. Stepwise regression was firstly applied in each environment to identify the most significant marker variables which were then used to adjust the phenotypic values. One-dimensional scanning was then conducted on the adjusted phenotypic values across the environments in order to detect QTL with either average effect or QEI effects, or both average effect and QEI effects. In this way, the genetic background could be well controlled while the conventional interval mapping was applied. An empirical method to determine the threshold of logarithm of odds was developed, and the efficiency of the ICIM QEI mapping was demonstrated in simulated populations under different genetic models. One actual recombinant inbred line population was used to compare mapping results between QEI mapping and single-environment analysis. PMID- 26161657 TI - The Effect of a Pro-Breastfeeding and Healthy Complementary Feeding Intervention Targeting Adolescent Mothers and Grandmothers on Growth and Prevalence of Overweight of Preschool Children. AB - INTRODUCTION: The pattern and duration of breastfeeding (BF) and the age at onset of complementary feeding, as well as its quality, have been associated with the prevalence of overweight in childhood. OBJECTIVE: To assess the effect of a pro BF and healthy complementary feeding intervention, targeted to adolescent mothers and maternal grandmothers, on growth and prevalence of overweight and obesity in children at preschool age. This intervention had a positive impact on duration of BF and timing of onset of complementary feeding. METHODS: This randomized clinical trial involved 323 adolescent mothers, their infants, and the infants' maternal grandmothers, when they cohabited. Mothers and grandmothers in the intervention group received counseling sessions on BF and healthy complementary feeding at the maternity ward and at home (7, 15, 30, 60, and 120 days after delivery). When children were aged 4 to 7 years, they underwent anthropometric assessment and collection of data on dietary habits. Multivariable Poisson regression with robust estimation was used for analysis. RESULTS: BMI-for-age and height-for-age were similar in the intervention and control groups, as was the prevalence of overweight (39% vs. 31% respectively; p=0.318). There were no significant between-group differences in dietary habits. CONCLUSION: Although the intervention prolonged the duration of exclusive BF and delayed the onset of complementary feeding, it had no impact on growth or prevalence of overweight at age 4 to 7 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT00910377. PMID- 26161658 TI - Long-Term Serological Follow-Up of Acute Q-Fever Patients after a Large Epidemic. AB - BACKGROUND: Serological follow-up of acute Q-fever patients is important for detection of chronic infection but there is no consensus on its frequency and duration. The 2007-2009 Q-fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients. The aim of this study was to validate the current follow-up strategy targeted to identify patients with chronic Q-fever. METHODS: A cohort of adult acute Q-fever patients, diagnosed between 2007 and 2009, for whom a twelve-month follow-up sample was available, was invited to complete a questionnaire and provide a blood sample, four years after the acute episode. Antibody profiles, determined by immunofluorescence assay in serum, were investigated with a special focus on high titres of IgG antibodies against phase I of Coxiella burnetii, as these are considered indicative for possible chronic Q-fever. RESULTS: Of the invited 1,907 patients fulfilling inclusion criteria, 1,289 (67.6%) were included in the analysis. At any time during the four-year follow-up period, 58 (4.5%) patients were classified as possible, probable, or proven chronic Q-fever according to the Dutch Q-fever Consensus Group criteria (which uses IgG phase I >=1:1,024 to as serologic criterion for chronic Q-fever). Fifty-two (89.7%) of these were identified within the first year after the acute episode. Of the six patients that were detected for the first time at four-year follow-up, five had an IgG phase I titre of 1:512 at twelve months. CONCLUSIONS: A twelve-month follow-up check after acute Q-fever is recommended as it adequately detects chronic Q-fever in patients without known risk factors. Additional serological and clinical follow-up is recommended for patients with IgG phase I >=1:512, as they showed the highest risk to progress to chronic Q-fever. PMID- 26161659 TI - Deep Characterization of the Microbiomes of Calophya spp. (Hemiptera: Calophyidae) Gall-Inducing Psyllids Reveals the Absence of Plant Pathogenic Bacteria and Three Dominant Endosymbionts. AB - Bacteria associated with sap-feeding insect herbivores include not only symbionts that may increase their hosts' fitness but also harmful plant pathogens. Calophya spp. gall-inducing psyllids (Hemiptera: Calophyidae) are being investigated for their potential as biological control agents of the noxious weed, Brazilian peppertree (Schinus terebinthifolia), in Florida. Although there are no examples of plant pathogen transmission by members of the family Calophyidae, several insects in the superfamily Psylloidea are known to transmit pathogenic bacteria in the genera Candidatus Liberibacter and Candidatus Phytoplasma. To determine whether Calophya spp. harbor potentially harmful plant pathogenic bacteria, we sequenced small subunit (SSU) ribosomal RNA (rRNA) gene amplicons generated from individuals from four Calophya spp. populations: All microbial SSU gene sequences fell into the bacterial domain, with 98-99% belonging to the Proteobacteria. The Calophya microbiomes contained a relatively simple community, with 49-79 operational taxonomic units (OTUs; 97%) detected, and only 5-8 OTUs with greater than 1% abundance. Candidatus Carsonella showed the highest relative abundance, with OTUs from this candidate genus representing between 51-65% of all recovered sequences. The next most abundant clade observed was an unclassified Enterobacteriacae group closely related to bacteria from the genera Buchnera and Blochmannia that ranged from 20-31% in relative abundance. Wolbachia populations were the third most abundant group and represented 7-27% of the diversity in microbial OTUs. No SSU rRNA gene sequences from putative pathogenic bacteria from the genera Ca. Liberibacter or Ca. Phytoplasma were detected in the microbiomes of the four Calophya populations. The probability that infected psyllids were present in our colonies, but were not sampled, was extremley low (1.39 x 10( 10)). As far as we are aware, our study is the first to characterize the microbiome of a candidate biological control agent, and coupled with previous work demonstrating a high degree of host specificity and absence of plant viruses, suggests that releasing Calophya spp. in United States poses minimal risk to non-target plants. PMID- 26161661 TI - An Analytical Model for the Distributions of Velocity and Discharge in Compound Channels with Submerged Vegetation. AB - Based on the momentum transfer theory, an analytical model is proposed for the velocity and discharge distributions in compound channels with submerged vegetation on the floodplain. The partially vegetated channel was divided into three sub-regions, i.e. the main channel region, the floodplain region with submerged vegetation and the floodplain region without vegetation. For each region, the force balance relationship was established, and the momentum transfer between different regions was presented. Verification by the experimental data and comparison with the traditional method shows that the proposed method is capable of predicting for the velocity and discharge distributions in compound channels with submerged vegetation and is superior to the conventional method. The results also show that when the momentum transfer between different regions is ignored, the computed discharge will be much lager than the measured data, and the error increases with the discharge, especially in the floodplain region. PMID- 26161660 TI - Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease. AB - Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an active dimeric form of the enzyme, which is believed to play a key regulatory role in the orchestration of proteolysis and capsid assembly. Currently available crystal structures of herpesvirus proteases correspond either to the dimeric state or to complexes with peptide mimetics that alter the dimerization interface. In contrast, the structure of the native monomeric state has remained elusive. Here, we present the three-dimensional structures of native monomeric, active dimeric, and diisopropyl fluorophosphate-inhibited dimeric protease derived from pseudorabies virus, an alphaherpesvirus of swine. These structures, solved by X-ray crystallography to respective resolutions of 2.05, 2.10 and 2.03 A, allow a direct comparison of the main conformational states of the protease. In the dimeric form, a functional oxyanion hole is formed by a loop of 10 amino acid residues encompassing two consecutive arginine residues (Arg136 and Arg137); both are strictly conserved throughout the herpesviruses. In the monomeric form, the top of the loop is shifted by approximately 11 A, resulting in a complete disruption of the oxyanion hole and loss of activity. The dimerization-induced allosteric changes described here form the physical basis for the concentration dependent activation of the protease, which is essential for proper virus replication. Small-angle X-ray scattering experiments confirmed a concentration dependent equilibrium of monomeric and dimeric protease in solution. PMID- 26161662 TI - Genetic Evidence for Function of the bHLH-PAS Protein Gce/Met As a Juvenile Hormone Receptor. AB - Juvenile hormones (JHs) play a major role in controlling development and reproduction in insects and other arthropods. Synthetic JH-mimicking compounds such as methoprene are employed as potent insecticides against significant agricultural, household and disease vector pests. However, a receptor mediating effects of JH and its insecticidal mimics has long been the subject of controversy. The bHLH-PAS protein Methoprene-tolerant (Met), along with its Drosophila melanogaster paralog germ cell-expressed (Gce), has emerged as a prime JH receptor candidate, but critical evidence that this protein must bind JH to fulfill its role in normal insect development has been missing. Here, we show that Gce binds a native D. melanogaster JH, its precursor methyl farnesoate, and some synthetic JH mimics. Conditional on this ligand binding, Gce mediates JH dependent gene expression and the hormone's vital role during development of the fly. Any one of three different single amino acid mutations in the ligand-binding pocket that prevent binding of JH to the protein block these functions. Only transgenic Gce capable of binding JH can restore sensitivity to JH mimics in D. melanogaster Met-null mutants and rescue viability in flies lacking both Gce and Met that would otherwise die at pupation. Similarly, the absence of Gce and Met can be compensated by expression of wild-type but not mutated transgenic D. melanogaster Met protein. This genetic evidence definitively establishes Gce/Met in a JH receptor role, thus resolving a long-standing question in arthropod biology. PMID- 26161664 TI - No Effects of Bilateral tDCS over Inferior Frontal Gyrus on Response Inhibition and Aggression. AB - Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression. While response inhibition is mostly associated with predominantly right prefrontal activity, the neural components underlying aggression seem to be left-lateralized. These differences in hemispheric dominance are conceptualized in cortical asymmetry theories on motivational direction, which assign avoidance motivation (relevant to inhibit responses) to the right and approach motivation (relevant for aggressive actions) to the left prefrontal cortex. The current study aimed to directly address the inverse relationship between response inhibition and aggression by assessing them within one experiment. Sixty-nine healthy participants underwent bilateral transcranial Direct Current Stimulation (tDCS) to the inferior frontal cortex. In one group we induced right-hemispheric fronto cortical dominance by means of a combined right prefrontal anodal and left prefrontal cathodal tDCS montage. In a second group we induced left-hemispheric fronto-cortical dominance by means of a combined left prefrontal anodal and right prefrontal cathodal tDCS montage. A control group received sham stimulation. Response inhibition was assessed with a go/no-go task (GNGT) and aggression with the Taylor Aggression Paradigm (TAP). We revealed that participants with poorer performance in the GNGT displayed more aggression during the TAP. No effects of bilateral prefrontal tDCS on either response inhibition or aggression were observed. This is at odds with previous brain stimulation studies applying unilateral protocols. Our results failed to provide evidence in support of the prefrontal cortical asymmetry model in the domain of response inhibition and aggression. The absence of tDCS effects might also indicate that the methodological approach of shifting cortical asymmetry by means of bilateral tDCS protocols has failed. PMID- 26161663 TI - Low Serum Neutrophil Gelatinase-associated Lipocalin Level as a Marker of Malnutrition in Maintenance Hemodialysis Patients. AB - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL or LCN2) is an iron transporting factor which possesses various activities such as amelioration of kidney injury and host defense against pathogens. Its circulating concentrations are elevated in acute and chronic kidney diseases and show a positive correlation with poor renal outcome and mortality, but its clinical significance in maintenance hemodialysis (HD) patients remains elusive. METHODS: Serum NGAL levels were determined by enzyme-linked immunosorbent assay in out-patient, Japanese HD subjects. Their correlation to laboratory findings and morbidity (as development of severe infection or serum albumin reduction) was investigated using linear regression analysis and chi2 test. RESULTS: Pre-dialysis serum NGAL levels in HD patients were elevated by 13-fold compared to healthy subjects (n=8, P<0.001). In a cross-sectional study of 139 cases, serum NGAL concentrations were determined independently by % creatinine generation rate (an indicator of muscle mass, standardized coefficient beta=0.40, P<0.001), peripheral blood neutrophil count (beta=0.38, P<0.001) and anion gap (which likely reflects dietary protein intake, beta=0.16, P<0.05). Iron administration to anemic HD patients caused marked elevation of peripheral blood hemoglobin, serum ferritin and iron regulatory hormone hepcidin-25 levels, but NGAL levels were not affected. In a prospective study of 87 cases, increase in serum albumin levels a year later was positively associated to baseline NGAL levels by univariate analysis (r=0.36, P<0.01). Furthermore, within a year, patients with the lowest NGAL tertile showed significantly increased risk for marked decline in serum albumin levels (>=0.4 g/dl; odds ratio 5.5, 95% confidence interval 1.5-20.3, P<0.05) and tendency of increased occurrence of severe infection requiring admission (odds ratio 3.1, not significant) compared to the middle and highest tertiles. CONCLUSION: Low serum NGAL levels appear to be associated with current malnutrition and also its progressive worsening in maintenance HD patients. PMID- 26161665 TI - The Still Bay and Howiesons Poort at Sibudu and Blombos: Understanding Middle Stone Age Technologies. AB - The classification of archaeological assemblages in the Middle Stone Age of South Africa in terms of diversity and temporal continuity has significant implications with respect to recent cultural evolutionary models which propose either gradual accumulation or discontinuous, episodic processes for the emergence and diffusion of cultural traits. We present the results of a systematic technological and typological analysis of the Still Bay assemblages from Sibudu and Blombos. A similar approach is used in the analysis of the Howiesons Poort (HP) assemblages from Sibudu seen in comparison with broadly contemporaneous assemblages from Rose Cottage and Klasies River Cave 1A. Using our own and published data from other sites we report on the diversity between stone artifact assemblages and discuss to what extent they can be grouped into homogeneous lithic sets. The gradual evolution of debitage techniques within the Howiesons Poort sequence with a progressive abandonment of the HP technological style argues against the saltational model for its disappearance while the technological differences between the Sibudu and Blombos Still Bay artifacts considerably weaken an interpretation of similarities between the assemblages and their grouping into the same cultural unit. Limited sampling of a fragmented record may explain why simple models of cultural evolution do not seem to apply to a complex reality. PMID- 26161666 TI - Outcomes of Estrogen Receptor Negative and Progesterone Receptor Positive Breast Cancer. AB - PURPOSE: To describe the clinical features and outcomes of estrogen receptor negative (ER-) and progesterone receptor positive (PgR+) breast cancer. METHODS: We retrospectively reviewed a well-characterized database of sequential patients diagnosed with early stage invasive breast carcinoma. Outcomes of interest were time to relapse (TTR) and overall survival (OS). Multivariable Cox proportional hazards analysis was conducted to assess the association of ER-/PgR+ with TTR and OS in comparison to ER+ and to ER- and PgR negative (ER-/PgR-) tumors irrespective of HER2 status. ER and PgR expression was conservatively defined as 10% or greater staining of cancer cells. RESULTS: 815 patients were followed for a median of 40.5 months; 56 patients (7%) had ER-/PgR+, 624 (77%) had ER+ and 136 (17%) had ER-/PgR- phenotypes. Compared with ER+ tumors, ER-/PgR+ tumors were associated with younger age (50 versus 59 years, p=0.03), high grade (50% versus 24%, p<0.001) and more frequent HER2 overexpression/amplification (43% versus 14%, p<0.001). TTR for ER-/PgR+ was intermediate between ER+ and ER-/PgR- tumors, but was not significantly different from ER+ tumors. Recurrences in the ER-/PgR+ and ER-/PgR- groups occurred early in follow-up while in ER+ tumors recurrences continued to occur over the duration of follow-up. OS of ER-/PgR+ was similar to ER+ tumors and better than that of ER-/PgR- tumors. CONCLUSIONS: The ER-/PgR+ phenotype is associated with higher grade with HER2 overexpression/amplification and occurs more commonly in younger women. Risk of relapse and death more closely resembles ER+ than ER-/PgR- tumors suggesting this phenotype represents a group of more aggressive hormone receptor positive tumors. PMID- 26161667 TI - An Automated, Adaptive Framework for Optimizing Preprocessing Pipelines in Task Based Functional MRI. AB - BOLD fMRI is sensitive to blood-oxygenation changes correlated with brain function; however, it is limited by relatively weak signal and significant noise confounds. Many preprocessing algorithms have been developed to control noise and improve signal detection in fMRI. Although the chosen set of preprocessing and analysis steps (the "pipeline") significantly affects signal detection, pipelines are rarely quantitatively validated in the neuroimaging literature, due to complex preprocessing interactions. This paper outlines and validates an adaptive resampling framework for evaluating and optimizing preprocessing choices by optimizing data-driven metrics of task prediction and spatial reproducibility. Compared to standard "fixed" preprocessing pipelines, this optimization approach significantly improves independent validation measures of within-subject test retest, and between-subject activation overlap, and behavioural prediction accuracy. We demonstrate that preprocessing choices function as implicit model regularizers, and that improvements due to pipeline optimization generalize across a range of simple to complex experimental tasks and analysis models. Results are shown for brief scanning sessions (<3 minutes each), demonstrating that with pipeline optimization, it is possible to obtain reliable results and brain-behaviour correlations in relatively small datasets. PMID- 26161668 TI - Mutant IDH1 Dysregulates the Differentiation of Mesenchymal Stem Cells in Association with Gene-Specific Histone Modifications to Cartilage- and Bone Related Genes. AB - Somatic mutations in the isocitrate dehydrogenase (IDH)1/2 genes endow encoding proteins with neomorphic activity to produce the potential oncometabolite, 2 hydroxyglutarate (2-HG), which induces the hypermethylation of histones and DNA. The incidence of IDH1/2 mutations in cartilaginous tumors was previously shown to be the highest among various types of tumors, except for those in the central nervous system. Mutations have been detected in both benign (enchondromas) and malignant (chondrosarcomas) types of cartilaginous tumors, whereas they have rarely been found in other mesenchymal tumors such as osteosarcomas. To address this unique tumor specificity, we herein examined the effects of IDH1 R132C, which is the most prevalent mutant in cartilaginous tumors, on the differentiation properties of human mesenchymal stem cells (hMSCs). The induction of the IDH1 R132C gene into MSCs markedly increased the amount of 2-HG and up regulated global histone methylation. The induction of IDH1 R132C promoted the chondrogenic differentiation of hMSCs by enhancing the expression of SOX9 and COL2A1 genes in association with an increase in the active mark (H3K4me3), but disrupted cartilage matrix formation. On the other hand, IDH1 R132C inhibited expression of the ALPL gene in association with an increase in the repressive mark (H3K9me3), and subsequently inhibited the osteogenic properties of hMSCs and human osteosarcoma cells. Since osteogenic properties are an indispensable feature for the diagnosis of osteosarcoma, the inhibitory effects of IDH1 R132C on osteogenic properties may contribute to the lack of osteosarcomas with the IDH1 R132C mutation. These results suggested that IDH1 R132C contributed to the formation of cartilaginous tumors by dysregulating the chondrogenic and osteogenic differentiation of hMSCs via gene-specific histone modulation. PMID- 26161669 TI - German Translation and Cross-Cultural Adaptation of the STarT Back Screening Tool. AB - BACKGROUND: Although evidence based treatment approaches for acute low back pain are available, the prevention of persistent disabling symptoms remains a challenge. Subgroup targeted treatment using adequate screening tools may be a key component for the development of new treatment concepts and is demonstrating promising early evidence. The Keele STarT Back Screening Tool is a practical instrument, developed to stratify patients with back pain according to their risk of persistent disabling symptoms. The aim of this study was to translate and cross-culturally adapt the STarT tool into German (STarT-G) and to investigate its psychometric properties. METHODS: The translation was performed according to internationally accepted guidelines and pretested to assess face validity among patients. Psychometric testing was then performed within a cross-sectional cohort of adult patients attending physiotherapy practices for back pain. Patients completed a booklet containing STarT-G and 5 reference standard questionnaires. Measurement properties of the STarT-G were explored including construct validity, floor and ceiling effects, and discriminative abilities. RESULTS: The pretests (n=25) showed good face validity including strong comprehension and acceptability of the STarT-G with only item 5 (fear avoidance) manifesting some ambiguities. The questionnaires were sent to 74 and completed by 50 patients (68%) of whom mean age was 46 (SD 14.5) years and 52% were male. Spearman's rank correlations for construct validity ranged from 0.35 to 0.56. AUCs for discriminative ability ranged from 0.79 to 0.91. Neither floor nor ceiling effects were observed. There were 28 (57%) participants defined as low risk, 17 (35%) as medium risk, and 4 (8%) as high risk. CONCLUSION: STarT-G is linguistically valid for German speaking countries. For the selected population, the correlations indicate acceptable validity and AUC showed satisfying discrimination. Data for psychometric properties have to be confirmed in a large scale study with a representative sample. PMID- 26161670 TI - Hepatitis E Virus Produced from Cell Culture Has a Lipid Envelope. AB - The absence of a productive cell culture system hampered detailed analysis of the structure and protein composition of the hepatitis E virion. In this study, hepatitis E virus from a robust HEV cell culture system and from the feces of infected monkeys at the peak of virus excretion was purified by ultra centrifugation. The common feature of the two samples after ultracentrifugation was that the ORF2 protein mainly remained in the top fractions. The ORF2 protein from cell culture system was glycosylated, with an apparent molecular weight of 88 kDa, and was not infectious in PLC/PRF/5 cells. The ORF2 protein in this fraction can bind to and protect HEV RNA from digestion by RNase A. The RNA-ORF2 product has a similar sedimentation coefficient to the virus from feces. The viral RNA in the cell culture supernatant was mainly in the fraction of 1.15 g/cm3 but that from the feces was mainly in the fraction of 1.21 g/cm3. Both were infectious in PLC/PRF/5 cells. And the fraction in the middle of the gradient (1.06 g/cm3) from the cell culture supernatant,but not that from the feces, also has ORF2 protein and HEV RNA but was not infectious in PLC/PRF/5.The infectious RNA-rich fraction from the cell culture contained ORF3 protein and lipid but the corresponding fraction from feces had no lipid and little ORF3 protein. The lipid on the surface of the virus has no effect on its binding to cells but the ORF3 protein interferes with binding. The result suggests that most of the secreted ORF2 protein is not associated with HEV RNA and that hepatitis E virus produced in cell culture differs in structure from the virus found in feces in that it has a lipid envelope. PMID- 26161671 TI - An Evolutionary View on Disulfide Bond Connectivities Prediction Using Phylogenetic Trees and a Simple Cysteine Mutation Model. AB - Disulfide bonds are crucial for many structural and functional aspects of proteins. They have a stabilizing role during folding, can regulate enzymatic activity and can trigger allosteric changes in the protein structure. Moreover, knowledge of the topology of the disulfide connectivity can be relevant in genomic annotation tasks and can provide long range constraints for ab-initio protein structure predictors. In this paper we describe PhyloCys, a novel unsupervised predictor of disulfide bond connectivity from known cysteine oxidation states. For each query protein, PhyloCys retrieves and aligns homologs with HHblits and builds a phylogenetic tree using ClustalW. A simplified model of cysteine co-evolution is then applied to the tree in order to hypothesize the presence of oxidized cysteines in the inner nodes of the tree, which represent ancestral protein sequences. The tree is then traversed from the leaves to the root and the putative disulfide connectivity is inferred by observing repeated patterns of tandem mutations between a sequence and its ancestors. A final correction is applied using the Edmonds-Gabow maximum weight perfect matching algorithm. The evolutionary approach applied in PhyloCys results in disulfide bond predictions equivalent to Sephiroth, another approach that takes whole sequence information into account, and is 26-29% better than state of the art methods based on cysteine covariance patterns in multiple sequence alignments, while requiring one order of magnitude fewer homologous sequences (10(3) instead of 10(4)), thus extending its range of applicability. The software described in this article and the datasets used are available at http://ibsquare.be/phylocys. PMID- 26161675 TI - Size-Tunable Organic Nanodot Arrays: A Versatile Platform for Manipulating and Imaging Cells. AB - Arrays of protein nanodots with dot-size tuned independently of spacing (e.g., ~100 to 600 nm diameter for 900 nm spacing) are fabricated. The mechanism of size control is demonstrated, by numerical simulations, to arise from shadow effects during deposition of a sacrificial metal mask. We functionalize the nanodots with antibodies and embed them in a polymer-cushion or in lipid-bilayers or transfer them to soft elastomers. Their ability to influence cell architecture and local membrane organization is demonstrated in T-lymphocytes, using reflection interference contrast and total internal reflection fluorescence microscopy. PMID- 26161672 TI - Nanocarrier for Oral Peptide Delivery Produced by Polyelectrolyte Complexation in Nanoconfinement. AB - The hydrophilic peptide YY (PYY) is a promising hormone-based antiobesity drug. We present a new concept for the delivery of PYY from pH-responsive chitosan based nanocarriers. To overcome the drawbacks while retaining the merits of the polyelectrolyte complex (PEC) method, we propose a one-pot approach for the encapsulation of a hydrophilic peptide drug in cross-linked PEC nanocarriers. First, the hydrophilic peptide is encapsulated via polyelectrolyte complexation within water-in-oil miniemulsion droplets. In a second step, the PEC surface is reinforced by controlled interfacial cross-linking. PYY is efficiently encapsulated and released upon pH change. Such nanocarriers are promising candidates for the fight against obesity and, in general, for the oral delivery of protein drugs. PMID- 26161676 TI - Pulmonary Rehabilitation and Physical Activity in Patients with Chronic Obstructive Pulmonary Disease. AB - Physical inactivity is common in patients with chronic obstructive pulmonary disease (COPD) compared with age-matched healthy individuals or patients with other chronic diseases. Physical inactivity independently predicts poor outcomes across several aspects of this disease, but it is (at least in principle) treatable in patients with COPD. Pulmonary rehabilitation has arguably the greatest positive effect of any current therapy on exercise capacity in COPD; as such, gains in this area should facilitate increases in physical activity. Furthermore, because pulmonary rehabilitation also emphasizes behavior change through collaborative self-management, it may aid in the translation of increased exercise capacity to greater participation in activities involving physical activity. Both increased exercise capacity and adaptive behavior change are necessary to achieve significant and lasting increases in physical activity in patients with COPD. Unfortunately, it is readily assumed that this translation occurs naturally. This concise clinical review will focus on the effects of a comprehensive pulmonary rehabilitation program on physical activity in patients with COPD. Changing physical activity behavior in patients with COPD needs an interdisciplinary approach, bringing together respiratory medicine, rehabilitation sciences, social sciences, and behavioral sciences. PMID- 26161677 TI - Theoretical and Experimental Study of the Crystal Structures, Lattice Vibrations, and Band Structures of Monazite-Type PbCrO4, PbSeO4, SrCrO4, and SrSeO4. AB - The crystal structures, lattice vibrations, and electronic band structures of PbCrO4, PbSeO4, SrCrO4, and SrSeO4 were studied by ab initio calculations, Raman spectroscopy, X-ray diffraction, and optical-absorption measurements. Calculations properly describe the crystal structures of the four compounds, which are isomorphic to the monazite structure and were confirmed by X-ray diffraction. Information is also obtained on the Raman- and IR-active phonons, with all of the vibrational modes assigned. In addition, the band structures and electronic densities of states of the four compounds were determined. All are indirect-gap semiconductors. In particular, chromates are found to have band gaps smaller than 2.5 eV and selenates higher than 4.3 eV. In the chromates (selenates), the upper part of the valence band is dominated by O 2p states and the lower part of the conduction band is composed primarily of electronic states associated with the Cr 3d and O 2p (Se 4s and O 2p) states. Calculations also show that the band gap of PbCrO4 (PbSeO4) is smaller than the band gap of SrCrO4 (SrSeO4). This phenomenon is caused by Pb states, which, to some extent, also contribute to the top of the valence band and the bottom of the conduction band. The agreement between experiments and calculations is quite good; however, the band gaps are underestimated by calculations, with the exception of the bang gap of SrCrO4, for which theory and calculations agree. Calculations also provide predictions of the bulk modulus of the studied compounds. PMID- 26161678 TI - Fabrication of a Core-Shell-Type Photocatalyst via Photodeposition of Group IV and V Transition Metal Oxyhydroxides: An Effective Surface Modification Method for Overall Water Splitting. AB - The design of optimal surface structures for photocatalysts is a key to efficient overall water splitting into H2 and O2. A unique surface modification method was devised for a photocatalyst to effectively promote overall water splitting. Photodeposition of amorphous oxyhydroxides of group IV and V transition metals (Ti, Nb, Ta) over a semiconductor photocatalyst from corresponding water-soluble metal peroxide complexes was examined. In this method, amorphous oxyhydroxide covered the whole surface of the photocatalyst particles, creating a core-shell structure. The water splitting behavior of the novel core-shell-type photocatalyst in relation to the permeation behavior of the coating layer was investigated in detail. Overall water splitting proceeded successfully after the photodeposition, owing to the prevention of the reverse reaction. The photodeposited oxyhydroxide layers were found to function as molecular sieves, selectively filtering reactant and product molecules. By exploiting the selective permeability of the coating layer, redox reactions on the photocatalyst surface could be suitably controlled, which resulted in successful overall water splitting. PMID- 26161679 TI - How Age, Linguistic Status, and the Nature of the Auditory Scene Alter the Manner in Which Listening Comprehension Is Achieved in Multitalker Conversations. AB - PURPOSE: We investigated how age and linguistic status affected listeners' ability to follow and comprehend 3-talker conversations, and the extent to which individual differences in language proficiency predict speech comprehension under difficult listening conditions. METHOD: Younger and older L1s as well as young L2s listened to 3-talker conversations, with or without spatial separation between talkers, in either quiet or against moderate or high 12-talker babble background, and were asked to answer questions regarding their contents. RESULTS: After compensating for individual differences in speech recognition, no significant differences in conversation comprehension were found among the groups. As expected, conversation comprehension decreased as babble level increased. Individual differences in reading comprehension skill contributed positively to performance in younger EL1s and in young EL2s to a lesser degree but not in older EL1s. Vocabulary knowledge was significantly and positively related to performance only at the intermediate babble level. CONCLUSION: The results indicate that the manner in which spoken language comprehension is achieved is modulated by the listeners' age and linguistic status. PMID- 26161681 TI - Lead exposure through consumption of big game meat in Quebec, Canada: risk assessment and perception. AB - Game meat from animals killed by lead ammunition may expose consumers to lead. We assessed the risk related to lead intake from meat consumption of white-tailed deer and moose killed by lead ammunition and documented the perception of hunters and butchers regarding this potential contamination. Information on cervid meat consumption and risk perception were collected using a mailed self-administrated questionnaire which was addressed to a random sample of Quebec hunters. In parallel, 72 samples of white-tailed deer (n = 35) and moose (n = 37) meats were collected from voluntary hunters and analysed for lead content using inductively coupled plasma-mass spectrometry. A risk assessment for people consuming lead shot game meat was performed using Monte Carlo simulations. Mean lead levels in white-tailed deer and moose killed by lead ammunition were 0.28 and 0.17 mg kg( 1) respectively. Risk assessment based on declared cervid meat consumption revealed that 1.7% of the surveyed hunters would exceed the dose associated with a 1 mmHg increase in systolic blood pressure (SBP). For consumers of moose meat once, twice or three times a week, simulations predicted that 0.5%, 0.9% and 1.5% of adults would be exposed to a dose associated with a 1 mmHg increase in SBP, whereas 0.9%, 1.9% and 3.3% of children would be exposed to a dose associated with 1 point intelligence quotient (IQ) decrease, respectively. For consumers of deer meat once, twice or three times a week, the proportions were 1.6%, 2.9% and 4% for adults and 2.9%, 5.8% and 7.7% for children, respectively. The consumption of meat from cervids killed with lead ammunition may increase lead exposure and its associated health risks. It would be important to inform the population, particularly hunters, about this potential risk and promote the use of lead-free ammunition. PMID- 26161682 TI - Multilayer Hydrophilic Poly(phenol-formaldehyde resin)-Coated Magnetic Graphene for Boronic Acid Immobilization as a Novel Matrix for Glycoproteome Analysis. AB - Capturing glycopeptides selectively and efficiently from mixed biological samples has always been critical for comprehensive and in-depth glycoproteomics analysis, but the lack of materials with superior capture capacity and high specificity still makes it a challenge. In this work, we introduce a way first to synthesize a novel boronic-acid-functionalized magnetic graphene@phenolic-formaldehyde resin multilayer composites via a facile process. The as-prepared composites gathered excellent characters of large specific surface area and strong magnetic responsiveness of magnetic graphene, biocompatibility of resin, and enhanced affinity properties of boronic acid. Furthermore, the functional graphene composites were shown to have low detection limit (1 fmol) and good selectivity, even when the background nonglycopeptides has a concentration 100 fold higher. Additionally, enrichment efficiency of the composites was still retained after being used repeatedly (at least three times). Better yet, the practical applicability of this approach was evaluated by the enrichment of human serum with a low sample volume of 1 MUL. All the results have illustrated that the magG@PF@APB has a great potential in glycoproteome analysis of complex biological samples. PMID- 26161683 TI - Cavity-Enhanced Raman Spectroscopy of Natural Gas with Optical Feedback cw-Diode Lasers. AB - We report on improvements made on our previously introduced technique of cavity enhanced Raman spectroscopy (CERS) with optical feedback cw-diode lasers in the gas phase, including a new mode-matching procedure which keeps the laser in resonance with the optical cavity without inducing long-term frequency shifts of the laser, and using a new CCD camera with improved noise performance. With 10 mW of 636.2 nm diode laser excitation and 30 s integration time, cavity enhancement achieves noise-equivalent detection limits below 1 mbar at 1 bar total pressure, depending on Raman cross sections. Detection limits can be easily improved using higher power diodes. We further demonstrate a relevant analytical application of CERS, the multicomponent analysis of natural gas samples. Several spectroscopic features have been identified and characterized. CERS with low power diode lasers is suitable for online monitoring of natural gas mixtures with sensitivity and spectroscopic selectivity, including monitoring H2, H2S, N2, CO2, and alkanes. PMID- 26161684 TI - Understanding the Control of Singlet-Triplet Splitting for Organic Exciton Manipulating: A Combined Theoretical and Experimental Approach. AB - Developing organic optoelectronic materials with desired photophysical properties has always been at the forefront of organic electronics. The variation of singlet triplet splitting (DeltaEST) can provide useful means in modulating organic excitons for diversified photophysical phenomena, but controlling DeltaEST in a desired manner within a large tuning scope remains a daunting challenge. Here, we demonstrate a convenient and quantitative approach to relate DeltaEST to the frontier orbital overlap and separation distance via a set of newly developed parameters using natural transition orbital analysis to consider whole pictures of electron transitions for both the lowest singlet (S1) and triplet (T1) excited states. These critical parameters revealed that both separated S1 and T1 states leads to ultralow DeltaEST; separated S1 and overlapped T1 states results in small DeltaEST; and both overlapped S1 and T1 states induces large DeltaEST. Importantly, we realized a widely-tuned DeltaEST in a range from ultralow (0.0003 eV) to extra-large (1.47 eV) via a subtle symmetric control of triazine molecules, based on time-dependent density functional theory calculations combined with experimental explorations. These findings provide keen insights into DeltaEST control for feasible excited state tuning, offering valuable guidelines for the construction of molecules with desired optoelectronic properties. PMID- 26161685 TI - Postoperative abdominal adhesions and bowel obstruction. A survey among Dutch general practitioners. AB - BACKGROUND: There is increasing interest among specialists in the complications after abdominal surgery due to adhesions. OBJECTIVE: Exploration of experiences, attitudes and expectations of general practitioners concerning bowel obstruction and postoperative abdominal adhesions. METHODS: In October 2012 a postal questionnaire was sent to a random sample of 800 Dutch GPs. RESULTS: The response rate was 45%, 24% (n = 190) filled out the questionnaire completely, 12% (n = 99) had no experience with the subject and 7% (n = 57) had no time to respond. A history of abdominal surgery does play a part in more than 80% of GP's differential diagnosis of abdominal complaints. Seventy-five per cent consider some types of surgery to induce more adhesions. Eighty-five per cent ponder the differentiation between adhesion related complaints and IBS as clear, however difficult (78%) in specific patients. Intestinal transit problems likely due to adhesions are treated with extra fluid (n = 64), more fibres (n = 85) and laxatives (n = 153). Referral to a specialist for adhesiolysis is rarely considered (11%). Forty per cent of the GPs would refer a patient with abdominal pain and suspected adhesions. Seventy-six per cent denote knowledge gaps and low experience in the treatment of intestinal transit problems. Some (n = 23) indicate the need for information about adhesions and obstruction through CME papers. CONCLUSION: Respondents are well equipped to deal with abdominal complaints and intestinal transit problems due to postoperative adhesions. Some indicate the need for information about adhesions and prevention of obstruction through CME papers. PMID- 26161686 TI - Life-Stage and Mobility: An Exploratory GPS Study of Mobility in Multigenerational Families, Ahmedabad, India. AB - As the population of older adults in India grows, research is needed to plan a sustainable future for India's older adults. This article reports results from a Global Positioning System (GPS)-based pilot study that examined the mobility of middle-class, older adults living in Ahmedabad, Gujarat, India. Using mobility as a lens through which to examine the lives of older adults, we map potential research and identify policy areas of interest considering older adults in urban India. The study explores the role of life stage in mobility as well as the effects of gender and urban environment on mobility. Using this distinctive perspective on day-to-day life, we propose themes through which, using policy and planning tools, the living environments of older adults in Indian cities can be improved. These policy measures include focusing on walkability and pedestrian safety in residential areas and building on existing mixed land use to create high accessibility to goods and services in urban environments. PMID- 26161687 TI - Simultaneous detection of endocrine disrupting chemicals including conjugates in municipal wastewater and sludge with enhanced sample pretreatment and UPLC-MS/MS. AB - The co-existence of free and conjugated estrogens and the interference from complex matrices often lead to largely variable detected concentrations and sometimes even negative removal efficiencies of typical endocrine disrupting chemicals (EDCs) in wastewater treatment plants (WWTPs). In this study, a highly selective and sensitive method was developed for simultaneous extraction, elution, and detection of 12 EDCs (i.e., 4 free estrogens, 6 conjugated estrogens, and 2 phenolic compounds) in municipal wastewater and sludge. Sample pretreatment and ultra-performance liquid chromatography-tandem mass spectrometry detection were optimized to improve the detection selectivity and sensitivity. The results indicate that the additional purification process was highly effective in reducing the matrix interference, and the limits of quantification reached as low as 0.04-2.2 ng L(-1) in wastewater and 0.05-4.9 ng g(-1) in sludge for all target EDCs. The developed method was successfully applied to explore the behavior of target EDCs in a local WWTP. The conjugates occupied a considerable portion (4.3-76.9% in molar ratio) of each related estrogen in the influent. Most of the target EDCs could not be completely removed in WWTPs, thus posing a potential threat to aquatic ecosystems. PMID- 26161688 TI - Extracellular Matrix Properties Regulate the Migratory Response of Glioblastoma Stem Cells in Three-Dimensional Culture. AB - Diffuse infiltration across brain tissue is a hallmark of glioblastoma and the main cause of unsuccessful total resection that leads to tumor reappearance. A subpopulation termed glioblastoma stem cells (GSCs) has been directly related to aggressive invasion; nonetheless, their migratory characteristics and regulation by the microenvironment are still unknown. In this study, we developed a composite matrix of hyaluronan (HA) structurally supported by a collagen-oligomer fibril network to simulate the brain tumor extracellular matrix (ECM) composition. Matrigel-coated microfibers were embedded within the matrix to create a tunable dual niche microenvironment that resembles the vascular network of the brain. This model was compared with the most commonly used in vitro three dimensional (3D) culture formats, Matrigel and collagen type-I monomer matrices, to study how the mechanical and compositional properties of the ECM alter the migration characteristics of GSC neurospheres. The migration mode, distance, velocity, and morphology of the GSCs were monitored over a 72-h period. The cells altered their migration mode depending on the matrix composition, showing migration by expansive growth in Matrigel matrices, multicellular extension along rigid interfaces (as Matrigel glass and coated microfibers), and mesenchymal single-cell migration in collagen matrices. Velocity and distance of migration within each composition varied according to matrix mechanical properties. In the dual niche system, the presence of HA reduced velocity and number of migratory cells; however, cells that came in contact with the pseudovessels exhibited collective migration by an extensive strand and reached higher velocities than cells migrating individually across the 3D matrix. Our results show that GSCs adopt varied migration mechanisms to invade multiple ECM microenvironments, and the migration characteristics exhibited are highly influenced by the matrix physical properties. Moreover, GSC neurospheres exhibit concomitant single and collective migration as a function of the microenvironment topography to reach the most productive migration strategy. PMID- 26161689 TI - Adsorption of 4-n-Nonylphenol and Bisphenol-A on Magnetic Reduced Graphene Oxides: A Combined Experimental and Theoretical Studies. AB - Adsorption of 4-n-nonylphenol (4-n-NP) and bisphenol A (BPA) on magnetic reduced graphene oxides (rGOs) as a function of contact time, pH, ionic strength and humic acid were investigated by batch techniques. Adsorption of 4-n-NP and BPA were independent of pH at 3.0- 8.0, whereas the slightly decreased adsorption was observed at pH 8.0-11.0. Adsorption kinetics and isotherms of 4-n-NP and BPA on magnetic rGOs can be satisfactorily fitted by pseudo-second-order kinetic and Freundlich model, respectively. The maximum adsorption capacities of magnetic rGOs at pH 6.5 and 293 K were 63.96 and 48.74 mg/g for 4-n-NP and BPA, respectively, which were significantly higher than that of activated carbon. Based on theoretical calculations, the higher adsorption energy of rGOs + 4-n-NP was mainly due to pi-pi stacking and flexible long alkyl chain of 4-n-NP, whereas adsorption of BPA on rGOs was energetically favored by a lying-down configuration due to pi-pi stacking and dispersion forces, which was further demonstrated by FTIR analysis. These findings indicate that magnetic rGOs is a promising adsorbent for the efficient elimination of 4-n-NP/BPA from aqueous solutions due to its excellent adsorption performance and simple magnetic separation, which are of great significance for the remediation of endocrine-disrupting chemicals in environmental cleanup. PMID- 26161691 TI - Chemical Sensing of 2D Graphene/MoS2 Heterostructure device. AB - We report the production of a two-dimensional (2D) heterostructured gas sensor. The gas-sensing characteristics of exfoliated molybdenum disulfide (MoS2) connected to interdigitated metal electrodes were investigated. The MoS2 flake based sensor detected a NO2 concentration as low as 1.2 ppm and exhibited excellent gas-sensing stability. Instead of metal electrodes, patterned graphene was used for charge collection in the MoS2-based sensing devices. An equation based on variable resistance terms was used to describe the sensing mechanism of the graphene/MoS2 device. Furthermore, the gas response characteristics of the heterostructured device on a flexible substrate were retained without serious performance degradation, even under mechanical deformation. This novel sensing structure based on a 2D heterostructure promises to provide a simple route to an essential sensing platform for wearable electronics. PMID- 26161690 TI - Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance. AB - Human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. Knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. Here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in Copenhagen, Denmark, from nine cities in three world regions. An average of 18.6 Gb (14.8 to 25.7 Gb) of raw Illumina paired end sequence data was generated, cleaned, trimmed and mapped against reference sequence databases for bacteria and antimicrobial resistance genes. An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples. We found significantly higher abundance and diversity of genes encoding antimicrobial resistance, including critical important resistance (e.g. blaCTX-M) carried on airplanes from South Asia compared to North America. Presence of Salmonella enterica and norovirus were also detected in higher amounts from South Asia, whereas Clostridium difficile was most abundant in samples from North America. Our study provides a first step towards a potential novel strategy for global surveillance enabling simultaneous detection of multiple human health threatening genetic elements, infectious agents and resistance genes. PMID- 26161692 TI - Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia-reperfusion injury. AB - BACKGROUND: The present study aimed to investigate whether the inflammatory and antioxidant lycopene has a therapeutic effect against renal ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: In this study, 24 Wistar-Albino rats, weighing from 200 to 250 g, were divided into four groups. All rats underwent median laparotomy under anesthesia. No procedures were performed in the control group (Group C), whereas 100 mg/kg lycopene was administered by gavage in the lycopene group (Group L). The arteries of both kidneys were clamped for 45 min in the ischemia group (Group I), whereas 100 mg/kg lycopene was administered by gavage 30 min before clamping renal arteries, and ischemia was performed in the treatment group (Group T) rats. For all rats, blood samples and renal tissues were collected at 6 h of reperfusion. Samples were used to examine serum BUN, creatinine, MDA and GSH levels, and the renal tissues were used to examine MDA and GSH levels, and renal histopathologies. RESULTS: The treatment group had statistically significant lower serum MDA levels, histopathological tubular vacuolization, loss of brush border and tubular dilatation (p < 0.05), whereas serum BUN, creatinine, tissue MDA, and tissue and serum GSH levels were improved in favor of the treatment group, even though it was not statistically significant (p > 0.05). CONCLUSION: The present study demonstrated that lycopene, which was administered prior to renal I/R injury, prevented renal damage through biochemical and histopathological parameters. PMID- 26161693 TI - Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus. AB - Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme that regulates nucleotide synthesis and DNA methylation. The MTHFR C677T gene polymorphism (rs1801133), a C -> T transition at nucleotide 677 in exon 4, is a common gene variant of MTHFR and has been implicated in diabetic nephropathy, albeit with inconsistent results. Here, we performed a meta-analysis to assess the common effect size of this polymorphism on DN susceptibility. Case-control studies on the association of the MTHFR C677T gene polymorphism with DN risk were retrieved from databases up to August 1, 2013, and eligible studies were recruited into the meta-analysis and further analyzed. Of 132 studies, 33 were identified as suitable for this analysis. The results showed that T allele and TT genotype were distinctly associated with DN susceptibility in the overall population and Asians, and might be a risk factor in Caucasians and Africans (T allele: Overall population: p < 0.00001, Asians: p = 0.0002, Caucasians: p = 0.02, Africans: p < 0.00001; TT genotype: Overall population: p < 0.00001, Asians: p = 0.0003, Caucasians: p = 0.008, Africans: p = 0.0003). Furthermore, the analysis suggested that the CC genotype might play a protective role against DN onset in patients with type 2 diabetes for the overall population, Asians, Caucasian and Africans. However, due to the limited sample size in the African population, these results should be interpreted with care. In conclusion, the MTHFR C677T T allele or TT genotype might be a significant genetic molecular marker to determine the risk of DN in patients with type 2 diabetes and help to develop suitable disease prevention and management strategies. PMID- 26161698 TI - Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014). AB - INTRODUCTION: Cell cycle deregulation is a common characteristic of cancer cells. Progression through the cell cycle is controlled by enzymes known as cyclin dependent kinases (CDKs), whose activity can be upregulated by a wide range of molecular mechanisms. Based on these observations, small molecule CDK inhibitors are being developed as potential cancer therapeutics. Some of these compounds have entered Phase III clinical trials and one of them, palbociclib, recently received accelerated approval from the FDA. However, the complexity of CDK biology and the undesired side effects of the existing inhibitors mean that the hunt for new CDK-targeting drug candidates continues. AREAS COVERED: This article reviews patent applications related to small molecule CDK inhibitors published between 2009 and 2014. EXPERT OPINION: Clinical trials with pan-specific inhibitors have generally yielded unambiguously positive outcomes. However, better results have been achieved with highly specific inhibitors of CDK4/CDK6. This may be due to several factors and has generated considerable interest in the discovery of new mono-specific CDK inhibitors. The development of such compounds is challenging because all CDKs have very similar active sites. Aside from this issue of selectivity, another key challenge is the identification of patients who will benefit from specific therapies. PMID- 26161699 TI - Analysis of the UHRF1 expression in serum and tissue for gastric cancer detection. AB - OBJECTIVE: To analyze the Ubiquitin-like with PHD and ring finger domains (UHRF) 1 expression in gastric cancer (GC). METHODS: The concentrations of UHRF1 DNA in serum were compared between 187 GC patients and 56 healthy controls using real time PCR. Immunohistochemical analysis using tissue microarrays was performed. RESULTS: UHRF1 DNA levels were significantly higher in GC patients compared to healthy controls (p < 0.001) and have associations with age and lymph node metastasis (LNM). The UHRF1 expression was significantly higher in tumor tissue than matched normal tissues (p < 0.001). CONCLUSIONS: The UHRF1 expression in serum and tissue may represent a novel biomarker for GC diagnosis and prognosis. PMID- 26161701 TI - Rapid detection of urinary long non-coding RNA urothelial carcinoma associated one using a PCR-free nanoparticle-based assay. AB - We developed a specific hybridization assay for direct detection of long non coding RNA urothelial carcinoma associated-1 (lncRNA-UCA1). Total RNA was extracted from urine pellet samples (bladder carcinoma patients and controls). Then, we compared the developed nanoassay with quantitative real time polymerase chain reaction (qRT-PCR) results in detection of urine UCA1 in bladder cancer and control samples. The sensitivity and the specificity of UCA1 nanoassay were 92.1% and 93.3%, respectively. The concordance of the two methods was 98%. Interestingly, all bilharzial benign cases showed negative lncRNA-UCA1 using both methods. UCA1-nanoassay is a valid test for direct detection of urine UCA1 for bladder cancer detection. PMID- 26161700 TI - Profile of the porcine acute-phase proteins response following experimental co infection with H3N2 swine influenza virus and Pasteurella multocida. AB - CONTEXT: Acute phase proteins (APPs) are proposed as potential markers of the health status in pigs. OBJECTIVE: Circulating APPs in pigs co-infected with swine influenza virus and Pasteurella multocida. METHODS: Serum APPs were measured in co-infected and control pigs with the use of commercial ELISA tests. RESULTS: All investigated APPs revealed significant changes in co-infected pigs during the study period. The concentration of C-reactive protein, haptoglobin and serum amyloid A (SAA) increased significantly at 2 dpi, before respiratory signs and fever were observed. Concentration of Pig-MAP increased significantly at 3 dpi. C reactive protein and SAA reaction were rapid but short-lived. The concentration of Hp and Pig-MAP in serum also increased at very early stage of co-infection but remained elevated for a longer period of time. CONCLUSIONS: Maximal concentration of serum amyloid A correlated with the disease severity in pigs. PMID- 26161702 TI - Association between polymorphisms in IL27 gene and renal cell carcinoma. AB - CONTEXT: Interleukin-27 is a new member of the IL-12 family which plays an important role in human carcinogenesis. OBJECTIVE: To investigate whether polymorphisms in IL27 contribute to renal cell carcinoma (RCC) risk. MATERIALS AND METHODS: These two polymorphisms were genotyped in 329 RCC patients and 386 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Significantly increased RCC risk was associated the G allele of both rs153109 and rs17855750 (rs153109: p = 0.006, OR = 1.364, 95%CI = 1.095-1.700; rs17855750: p = 0.001, OR = 1.768, 95%CI = 1.245-2.511). CONCLUSION: The present study provided evidence that rs153109 and rs17855750 were associated with increased risk for RCC, suggesting an important role IL-27 may play in nephrocarcinogenesis. PMID- 26161703 TI - Multipotent SSEA1 Positive Cells Population Differentiation into Primordial Germ Cells and Subsequently Progress into Oocyte-like Cells. AB - BACKGROUND: Stage-specific embryonic antigen-1 (SSEA1) is a cell surface carbohydrate that its pattern expression is changed during induction of mouse embryonic stem cell differentiation. In this study, the spatial distribution of SSEA1 on primordial germ cells differentiation and subsequent progression into oocyte-like cells from mouse embryonic stem cells in vitro was evaluated. METHODS: Embryoid bodies from mouse embryonic stem cells were cultured for two days with 5 ng/mL BMP4. SSEA1 positive and negative cells were separated using the MACS system and cultured separately in a conditioned medium consist of in vitro maturation medium diluted in DMEM [1:1] for 10 days. We assayed viability, colony formation and alkaline phosphatase activity (ALP) of sorted cells. Also, germ cell markers were analyzed by flow cytometry, immunocytochemistry and RT PCR. RESULTS: Viability percent SSEA1 positive cells were more than SSEA1 negative cells. SSEA1 positive cells and SSEA1 negative cells formed compact and flat colonies respectively. Unlike the SSEA1 positive population, the SSEA1 negative colonies showed a weak ALP activity. SSEA1 positive cells expressed Oct4, Stella, Mvh, c-kit, Scp3, Desmin, GFAP and Albumin. Interestingly, SSEA1 negative cells expressed Desmin and GFAP. The population of Mvh-positive cells in SSEA1 positive was 17.74%. All specific oocyte mentioned genes were detected in the SSEA1 positive. Also, oocyte specific proteins GDF9 and ZP3 were detected using immunocytochemistry. CONCLUSION: Our results suggest that conditioned medium provides a suitable niche to differentiation and progression putative primordial germ cells derived from the SSEA1 positive toward oocyte-like cells. PMID- 26161704 TI - A Suggested Prototype for Assessing Bone Health. AB - BACKGROUND: Osteoporosis is becoming a health concern worldwide. Considering the fact that prevention plays an important role in reducing the burden of this silent disease and in view of the limited resources available, many countries have adopted certain programs to fight osteoporosis through shifting their attention towards at-risk individuals. The Iranian Multicenter Osteoporosis Study (IMOS) is one of these programs. The program aims to assess bone health and the prevalence of vitamin D deficiency in different parts of Iran with various altitudes, latitudes and lifestyle habits in a way that the results could be generalized to the country. METHOD: The present article presents the protocol used in the third phase of the study. It was designed based on the experiences gathered in the previous phases to overcome the shortcomings particularly subject loss. The questionnaire applied in this study was developed based on a thorough literature review of the risk factors and secondary causes of osteoporosis and was approved by an expert panel. RESULTS: While the majority of the existing studies aim to study a certain aspect of osteoporosis, the present protocol provides the information needed for policy makers and researchers to study different osteoporosis-related issues. CONCLUSION: The authors believe the protocol, to be implemented with small modifications, can help policymakers in different parts of the world, particularly developing countries, gather accurate information on different aspects of bone health at the national level. PMID- 26161705 TI - Opening the Black Box: The Experiences and Lessons From the Public Hospitals Autonomy Policy in Iran. AB - INTRODUCTION: Policy formulation and adoption often happen in a black box. Implementation challenges affect and modify the nature of a policy. We analyzed hospitals' autonomy policy in Iran that was intended to reduce hospitals' financial burden on government and improve their efficiency. METHODS: We followed a retrospective case-study methodology, involving inductive and deductive analyses of parliamentary proceedings, policy documents, gray literature, published papers and interview transcripts. We analyzed data to develop a policy map that included important dates and events leading to the policy process milestones. RESULTS: We identified four time-periods with distinctive features: 'moving toward the policy' (1989 - 1994), disorganized implementation' (1995 - 1997), 'continuing challenges and indecisiveness in hospitals financing' (1998 - 2003), and 'other structural and financial policies in public hospitals' (2004 to date). We found that stakeholders required different and conflicting objectives, which certainly resulted in an unsatisfactory implementation process. The policy led to long-lasting and often negative changes in the hospital sector and the entire Iranian health system. CONCLUSION: Hospital autonomy appeared to be an ill advised policy to remedy the inefficiency problems in low socioeconomic areas of the country. The assumption that hospital autonomy reforms would necessarily result in a better health system, may be a false assumption as their success relies on many contextual, structural and policy implementation factors. PMID- 26161706 TI - Type I and Type II Hereditary Angioedema: Clinical and Laboratory Findings in Iranian Patients. AB - BACKGROUND: Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by C1-INH (C1 esterase inhibitor), low serum levels (type I), dysfunction (type II) or normal serum levels and function (type III), which lead to subcutaneous and submucosal edema attacks. The aim of this study was to investigate the demographic, clinical and laboratory findings of Iranian patients with HAE. METHODS: The patients with a history or symptoms of angioedema who were referred to Immunology, Asthma and Allergy Research Institute (IAARI) between Jan 2006 and Jan 2014, were assessed based on a specific questionnaire and laboratory evaluation. The patients with a definite diagnosis of HAE type I and type II were entered into this study. RESULTS: Among 51 patients, 63.3% were diagnosed with HAE type I and 36.7% with HAE type II. Fifteen patients were under 18 years and 36 were adults. The mean age of symptoms onset and diagnosis were 12.33 +/- 10.20 years and 24.48 +/- 14.64 years, respectively. The mean delay of diagnosis was 11.02 +/- 11.60 years. The most commonly involved locations of edema were hands, face and genitalia. Moreover, laryngeal edema was observed in 61.2% of patients, which led to death in two patients during this study. CONCLUSION: Hereditary angioedema is a life threatening disease with considerable morbidity and mortality. The outcomes of this study can be used to inform clinicians and health care providers about HAE, which can help earlier diagnosis and better management of the patients, specifically in life threatening attacks. PMID- 26161707 TI - Evaluation of Appropriate and Inappropriate Admission and Hospitalization Days According to Appropriateness Evaluation Protocol (AEP). AB - BACKGROUND: Inappropriate admission and hospitalization days are the factors that impose more costs to hospitals. By considering current condition of hospitals, it is vital to have an insight into the data on inappropriate admission and hospitalization days in order to eliminate obstacles to the proper and appropriate hospitalization. METHODS: In this study, 198 patients who were admitted to receive surgical or non-surgical treatment in Sina public hospital were selected. An appropriateness Evaluation Protocol (AEP) was used for data collection. The validity of AEP is well established by the preceding studies. In order to achieve the study objectives, binary logistic regression test was used. RESULTS: According to our findings, 39.4% of hospitalization days and 16.2% of admissions are inappropriate. In this study, inappropriate admission was observed among married patients eight times more than among single ones. Inappropriate hospitalization days were 12 times more prevalent among patients from provinces than among those from Tehran. With increasing age of the patient the probability of inappropriate admission decreases slightly, i.e. the probability of inappropriate admission decreases 10% as the age increases one year. The number of hospitalization days was significantly correlated to the following parameters: type of admission, patient's city of residence, type of treatment, and length of stay (P < 0.05). CONCLUSION: Regarding the results of this study, a large number of admissions and specially hospitalization days are inappropriate. According to other studies, with suitable programming many inappropriate admissions and hospitalization days are preventable. PMID- 26161708 TI - Impact of Vitamin A Supplementation on Disease Progression in Patients with Multiple Sclerosis. AB - BACKGROUND: Many studies have shown that active vitamin A derivatives suppress the formation of pathogenic T cells in multiple sclerosis (MS) patients. The aim of the present study is to determine the impact of vitamin A on disease progression in MS patients. METHODS: A total of 101 relapsing-remitting MS (RRMS) patients were enrolled in a 1-year placebo-controlled randomized clinical trial. The treated group received 25000 IU/d retinyl palmitate for six month followed by 10000 IU/d retinyl palmitate for another six month. The results of the expanded disability status scale (EDSS) and multiple sclerosis functional composite (MSFC) were recorded at the beginning and the end of the study. The relapse rate was recorded during the intervention. Patients underwent baseline and follow up brain MRIs. RESULTS: The results showed "Mean +/- SD" of MSFC changes in the treated group was (-0.14 +/- 0.20) and in the placebo group was (-0.31 +/- 0.19). MSFC was improved significantly (P < 0.001) in the treatment group. There were no significant differences between the "Mean +/- SD" of EDSS changes in the treated (0.07 +/- 0.23) and placebo (0.08 +/- 0.23) groups (P = 0.73). There were also no significant differences between the "Mean +/- SD" of annualized relapse rate in the treated group (-0.36 +/- 0.56) and placebo (-0.53 +/- 0.55) groups (P = 0.20). The "Mean +/- SD" of enhanced lesions in the treatment (0.4 +/- 1.0) and in the placebo (0.2 +/- 0.6) groups were not significantly different (P = 0.26). Volume of T2 hyperintense lesions "Mean +/- SD" was not significantly different between treatment (45 +/- 137) and placebo (23 +/- 112) groups after intervention (P = 0.23). CONCLUSION: Vitamin A improved total MSFC score in RRMS patients, but it did not change EDSS, relapse rate and brain active lesions. PMID- 26161709 TI - Single Use of Itraconazole Has No Effect on Treatment for Penicillium Marneffei with HIV Infection. AB - OBJECTIVE: To evaluate the efficacy of a single use of itraconazole for treating Penicillium marneffei infection in HIV-infected patients, help to develop a clinical medication regimen, and provide a scientific basis for treatment measures. METHOD: A computerised literature search was carried out using the PubMed, EMbase, Ovid, Web of Science, Science Direct and CNKI (China National Knowledge Infrastructure) databases to collect relevant articles (from their establishment date to August 2014) using the following keywords: Itraconaz or Sporanox, HIV, AIDS, Penicillium marneffei (PSM), and Treatment. All related RCTs (Randomised Controlled Trials) were screened. Stata12.0 was used to conduct the meta-analysis to calculate the RR (relative risk) and 95% CI (confidence intervals). After that the consistency test, followed by the bias. RESULTS: Five RCT papers were finally enrolled, with 467 persons in total. Among them, 192 individuals were enrolled in the experimental group, of which 37 individuals (19.27%) died during the course of the study. The number of participants in the control group was 275, and of these, 55 individuals (18.55%) died over the course of the study. The meta-analysis showed that the RR and 95% CI was 1.03 and 0.69 1.54, P > 0.05, indicating that single-use itraconazole for the treatment of Penicillium marneffei infection in HIV-infected patients was non-effective. The publication bias analysis results showed that the funnel chart was symmetrical, indicating that the effect of publication bias in this research can be ignored. CONCLUSION: Single-use of itraconazole for the treatment of Penicillium marneffei infection in HIV-infected patients is non-effective. PMID- 26161710 TI - Novel Missense Mutation at Codon 2774 (C.8321 G>A) p.S2774N of APC Gene in a Denovo Case of Familial Adenomatous Polyposis. AB - Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease caused by germline mutation in Adenomatous Polyposis Coli (APC) gene. FAP accounts less than 1% of all colorectal cancers incidence. Patients generally present hundreds to thousands of adenomas in colon and rectum and develop colorectal cancer by age 35 - 40 if left untreated. A milder form of FAP with fewer numbers of polyps (< 100) is Attenuated FAP (AFAP) and in comparison with classical FAP, it usually diagnosed at an older age. Approximately 15% - 20% of FAP patients are ''de novo'' cases without any family history of the disease and novel APC mutations account for approximately 25% of FAP cases. In our study, we reported a novel missense mutation at the APC gene in a denovo patient with AFAP like phenotype. PMID- 26161711 TI - Acquired Hypertrichosis Lanuginosa: Typical Presentation and Unusual Association. AB - Paraneoplastic syndrome might be the first clinical manifestation of malignancy. We present a menopausal female with the acquired hypertrichosis lanuginosa (AHL) as an initial clinical presentation of rectal adenocarcinoma, unusually associated with paraneoplastic cerebellar degeneration (PCD) and disseminated intravascular coagulation (DIC). PMID- 26161712 TI - Idiopathic Choroidal Neovascularization in a 23-Year-Old Girl. AB - A 23-year-old girl presented with blurred vision in her left eye since 2 months ago. Her past medical history was unremarkable. On presentation, her left best corrected visual acuity was 20/80. Anterior segment exam was unremarkable. Posterior segment exam showed an ill-defined green gray elevation in the fovea with surrounding subretinal fluid. The right eye exam was normal. Fluorescein Angiography and Optic Coherence Tomography of the left eye was compatible with Choroidal Neovascularization (CNV). PMID- 26161713 TI - Numerous Bladder Stones. AB - An 83-year-old man with benign prostatic hyperplasia and several comorbid conditions presented with irremovable urethral Foley catheter. Plain abdominal X ray revealed a bladder full of stones. The patient had bilateral hydronephrosis and elevated serum Creatinine level. Open vesicolithotomy was done and more than 720 stones in various shapes and sizes was removed. After removal of stone, Creatinine gradually decreased from 4.9 to 1.8 mg/dL and most of lower urinary tract symptoms were alleviated in the follow-up. PMID- 26161714 TI - Professor Abass Alavi, Distinguished Medical Scientist. PMID- 26161715 TI - MALDI mass spectrometric imaging meets "omics": recent advances in the fruitful marriage. AB - Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI MSI) is a method that allows the investigation of the molecular content of surfaces, in particular, tissues, within its morphological context. The applications of MALDI MSI in the field of large-scale mass spectrometric studies, which are typically denoted by the suffix "omics", are steadily increasing. This is because, on the one hand, technical advances regarding sample collection and preparation, matrix application, instrumentation, and data processing have enhanced the molecular specificity and sensitivity of MALDI MSI; on the other hand, the focus of the "omics" community has moved from establishing an inventory of certain compound classes to exploring their spatial distribution to gain novel insights. Thus, the aim of this mini-review is twofold, to display the state-of the-art in terms of technical aspects in MALDI MSI and to highlight selected applications in the last two years, which either have significantly advanced a certain "omics" field or have introduced a new one through pioneering efforts. PMID- 26161716 TI - Performance evaluation of a 90 degrees -rotating dual-head small animal PET system. AB - Dual-head PET system suffers from poor resolution in the dimension perpendicular to the detector heads and vastly increased computations required by the accurate estimation of the system response matrix (SRM). The problem of poor x-axis resolution is caused by missing data owing to the intrinsic geometry flaws of the dual-head PET, which leads to high SRM similarity between the adjacent voxels along the x-axis. To compensate for this problem, our dual-head PET system prototype incorporates a [Formula: see text]-rotating mechanism. In addition, the cubic field of view (FOV) and cubic voxels are adopted to achieve a better geometrical symmetry, which avoids the re-estimation of SRM after rotation. The spatial resolution, sensitivity, noise equivalent count rate, scatter fraction and pileup fraction under different head separation distances were evaluated by a series of simulations, and the results were compared with those of the non rotation system. The SRM was estimated using the Monte Carlo method and the three dimensional images were reconstructed using the ordered subsets expectation maximization algorithm. Experimental results reveal a significantly improved x axis resolution via the proposed rotation mechanism. Our system can achieve x axis spatial resolution of 0.79 mm, 0.74 mm and 0.72 mm at the center of FOV under the head separation distance of 5 cm, 10 cm and 15 cm, respectively. PMID- 26161717 TI - Ethnicity and craniosynostosis. PMID- 26161718 TI - Ventriculoiliac shunt: a single case experience. PMID- 26161719 TI - Minimizing bone gaps when using custom pediatric cranial implants is associated with implant success. AB - OBJECT: Occasionally after a craniotomy, the bone flap is discarded (as in the case of osteomyelitis) or is resorbed (especially after trauma), and an artificial implant must be inserted in a delayed fashion. Polyetheretherketone (PEEK) implants and hard-tissue replacement patient-matched implants (HTR-PMI) are both commonly used in such cases. This study sought to compare the failure rate of these 2 implants and identify risk factors of artificial implant failure in pediatric patients. METHODS: This was a retrospective cohort study examining all pediatric patients who received PEEK or HTR-PMI cranioplasty implants from 2000 to 2013 at a single institution. The authors examined the following variables: age, sex, race, mechanism, surgeon, posttraumatic hydrocephalus, time to cranioplasty, bone gap width, and implant type. The primary outcome of interest was implant failure, defined as subsequent removal and replacement of the implant. These variables were analyzed in a bivariate statistical fashion and in a multivariate logistic regression model for the significant variables. RESULTS: The authors found that 78.3% (54/69) of implants were successful. The mean patient age was 8.2 years, and a majority of patients were male (73%, 50/69); the mean follow-up for the cohort was 33.3 months. The success rate of the 41 HTR-PMI implants was 78.1%, and the success rate of the 28 PEEK implants was 78.6% (p = 0.96). Implants with a bone gap of > 6 mm were successful in 33.3% of cases, whereas implants with a gap of < 6 mm had a success rate of 82.5% (p = 0.02). In a multivariate model with custom-type implants, previous failed custom cranial implants, time elapsed from previous cranioplasty attempt, and bone gap size, the only independent risk factor for implant failure was a bone gap > 6 mm (odds ratio 8.3, 95% confidence interval 1.2-55.9). CONCLUSIONS: PEEK and HTR-PMI implants appear to be equally successful when custom implantation is required. A bone gap of > 6 mm with a custom implant in children results in significantly higher artificial implant failure. PMID- 26161720 TI - Telescoped Synthesis of 2-Acyl-1-aryl-1,2-dihydroisoquinolines and Their Inhibition of the Transcription Factor NF-kappaB. AB - A sequential single-flask multicomponent reactions is highly effective for the synthesis of 1,2-dihydroisoquinolines through amidealkylation from intermediate N acylisoquinolinium salts under mild conditions. N-Acylisoquinolinium ions and trichloromethyl-1-(1H-indol-3-yl)isoquinoline-2(1H)-carboxylate have demonstrated their reactivity toward aromatic and aliphatic pi-nucleophiles. One of the 1,2 dihydroisoquinoline derivatives was found to be a potent inhibitor for transcription factor NF-kappaB by blocking IkappaBalpha degradation, p65 nuclear translocation, and NF-kappaB DNA binding in TNF-alpha-induced NIH 3T3 cells. PMID- 26161721 TI - MORTALITY PATTERNS IN ENDANGERED HAWAIIAN GEESE (NENE; BRANTA SANDVICENSIS). AB - Understanding causes of death can aid management and recovery of endangered bird populations. Toward those ends, we systematically examined 300 carcasses of endangered Hawaiian Geese (Nene; Branta sandvicensis) from Hawaii, Maui, Molokai, and Kauai between 1992 and 2013. The most common cause of death was emaciation, followed by trauma (vehicular strikes and predation), and infectious/inflammatory diseases of which toxoplasmosis (infection with Toxoplasma gondii) predominated. Toxicoses were less common and were dominated by lead poisoning or botulism. For captive birds, inflammatory conditions predominated, whereas emaciation, trauma, and inflammation were common in free-ranging birds. Mortality patterns were similar for males and females. Trauma predominated for adults, whereas emaciation was more common for goslings. Causes of death varied among islands, with trauma dominating on Molokai, emaciation and inflammation on Kauai, emaciation on Hawaii, and inflammation and trauma on Maui. Understanding habitat or genetic related factors that predispose Nene (particularly goslings) to emaciation might reduce the impact of this finding. In addition, trauma and infection with T. gondii are human-related problems that may be attenuated if effectively managed (e.g., road signs, enforcement of speed limits, feral cat [Felis catus] control). Such management actions might serve to enhance recovery of this endangered species. PMID- 26161722 TI - Morbidity and Mortality of Reptiles Admitted to the Australian Wildlife Health Centre, Healesville Sanctuary, Australia, 2000-13. AB - Medical records of 931 reptiles admitted to the Australian Wildlife Health Centre, Healesville Sanctuary, Healesville, Victoria, Australia, from 2000 to 2013 were reviewed to determine the causes of morbidity and mortality. Thirty nine species were presented; the most common were the common long-neck turtle (Chelodina longicollis; n = 311, 33.4%), the eastern bluetongue lizard (Tiliqua scincoides; n = 224, 4.1%), the blotched bluetongue lizard (Tiliqua nigrolutea; n = 136, 14.6%), and the lowland copperhead (Austrelaps superbus; n = 55, 5.9%). Trauma was the most significant reason for admissions, accounting for 73.0% of cases. This was followed by not injured (11.7%), displacement (6.4%), snake removal (4.2%), human interference (3.1%), introduced species (1.1%), sick/diseased (0.2%), and illegal pet (0.2%). Within the category of trauma, impact with motor vehicle (41.0% of trauma cases) and domestic animal attack (33.2% of trauma cases) were the most common subcategories. Our results indicate that indirect anthropogenic factors are a significant cause of morbidity and mortality in Australian reptiles. PMID- 26161723 TI - Evaluation of a Commercial ELISA for the Detection of Antibodies to Sarcoptes scabiei in Wild Boar (Sus scrofa). AB - Sarcoptic mange occurs in free-ranging wild boar (Sus scrofa) but has been poorly described in this species. We evaluated the performance of a commercial indirect enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of sarcoptic mange in domestic swine when applied to wild boar sera. We tested 96 sera from wild boar in populations without mange history ("truly noninfected") collected in Switzerland between December 2012 and February 2014, and 141 sera from free ranging wild boar presenting mange-like lesions, including 50 live animals captured and sampled multiple times in France between May and August 2006 and three cases submitted to necropsy in Switzerland between April 2010 and February 2014. Mite infestation was confirmed by skin scraping in 20 of them ("truly infected"). We defined sensitivity of the test as the proportion of truly infected that were found ELISA-positive, and specificity as the proportion of truly noninfected that were found negative. Sensitivity and specificity were 75% and 80%, respectively. Success of antibody detection increased with the chronicity of lesions, and seroconversion was documented in 19 of 27 wild boar sampled multiple times that were initially negative or doubtful. In conclusion, the evaluated ELISA has been successfully applied to wild boar sera. It appears to be unreliable for early detection in individual animals but may represent a useful tool for population surveys. PMID- 26161724 TI - Serologic Survey of Snowshoe Hares (Lepus americanus) in the Greater Yellowstone Area for Brucellosis, Tularemia, and Snowshoe Hare Virus. AB - We examined sera from snowshoe hares (Lepus americanus) livetrapped in the northern Greater Yellowstone Area (GYA), US, for antibodies to Brucella abortus, Francisella tularensis, and snowshoe hare virus (SSHV). Zero of 90, 0 of 67, and 40 of 100 samples were antibody positive for B. abortus, F. tularensis, and SSHV, respectively. Hares were trapped from 2009 to 2012, and of the six animals that were captured twice with at least 1 yr between captures, four developed antibody to SSHV, indicating active exposure to the agent. These findings suggest snowshoe hares in the GYA do not play a significant role as a reservoir of B. abortus, but do maintain the zoonotic, encephalitic SSHV in the population. PMID- 26161725 TI - Colloidal Defect-Free Silicalite-1 Single Crystals: Preparation, Structure Characterization, Adsorption, and Separation Properties for Alcohol/Water Mixtures. AB - In this work, colloidal silicalite-1 single crystals are for the first time synthesized using fluoride as mineralizing agent at near neutral pH. SEM, TEM, DLS, XRD, solid-state (29)Si MAS NMR, and adsorption/desorption experiments using nitrogen, water, n-butanol, and ethanol as adsorbates were used to characterize the crystals. The single crystals have a platelike habit with a length of less than 170 nm and an aspect ratio (length/width) of about 1.2, and the thickness of the crystals is less than 40 nm. Compared with silicalite-1 crystals grown using hydroxide as mineralizing agent, the amount of structural defects in the lattice is significantly reduced and the hydrophobicity is increased. Membrane separation and adsorption results show that the synthesized defect-free crystals present high selectivity to alcohols from alcohol/water mixtures. The n-butanol/water adsorption selectivities were ca. 165 and 14 for the defect-free crystals and a reference sample containing defects, respectively, illustrating the improvement in n-butanol/water selectivity by eliminating the polar silanol defects. PMID- 26161726 TI - Examining the Principles of Influence on Safer Sex Communication During Casual and Committed Sexual Encounters. AB - Teens and young people are at risk for contracting sexually transmitted infections. Understanding how relationship context may moderate the effectiveness of safer sex communication strategies among this demographic is important information for practitioners striving to promote safer sex behaviors. In this study, focus groups (N = 9) with college students were conducted and analyzed to examine the relation between 6 principles of influence (authority, consistency, liking, reciprocity, scarcity, and social proof) and safer sex communication during committed and casual sexual encounters. Results revealed that with the exceptions of social proof and consistency, the principles of influence were endorsed more frequently for casual than committed sexual encounters. For casual sexual encounters, the principles of authority, reciprocity, and scarcity arose as influential principles. For committed sexual encounters, the principles of consistency, liking, and reciprocity arose as influential principles. These results are discussed with an emphasis on the theoretical and practical implications. PMID- 26161727 TI - Hierarchically Porous Polymer Monoliths by Combining Controlled Macro- and Microphase Separation. AB - The ability to tune polymer monolith porosity on multiple length scales is desirable for applications in liquid separations, catalysis, and bioengineering. To this end, we have developed a facile synthetic route to nanoporous polymer monoliths based on controlled polymerization of styrene and divinylbenzene from a poly(lactide) macro-chain transfer agent in the presence of nonreactive poly(ethylene oxide) (PEO). Simple variations in the volume fraction and/or molar mass of PEO lead to either polymerization-induced microphase separation or simultaneous macro- and microphase separation. These processes dictate the resultant morphology and allow for control of the macro- and microstructure of the monoliths. Subsequent selective etching produces monoliths with morphologies that can be tailored from mesoporous, with control over mesopore size, to hierarchically meso- and macroporous, with percolating macropores. This convenient synthetic route to porous polymer monoliths has the potential to be useful in applications where both rapid mass transport and a high surface area are required. PMID- 26161728 TI - Catalytically Important Residues of E6AP Ubiquitin Ligase Identified Using Acid Cleavable Photo-Cross-Linkers. AB - Inactivation of the E6AP E3 ubiquitin ligase (UBE3A gene) causes Angelman syndrome, while aberrant degradation of p53 by E6AP is implicated in cervical cancers. Herein, we describe the development of photo-cross-linkers to discover catalytic residues of E6AP. Using these cross-linkers, we identified covalent modifications of the E6AP catalytic cysteine and two lysines: Lys(847) and Lys(799). Lys(847) is required for the formation of Lys(48)-linked polyubiquitin chains, while the K799A E6AP mutant was more active at producing Lys(48)-linked polyubiquitin chains. Thus, opposing roles of Lys(799) and Lys(847) pave the path forward to pharmacological inhibitors or activators of E6AP for therapeutic purposes. PMID- 26161730 TI - Palladium-Catalyzed Triple Successive C-H Functionalization: Direct Synthesis of Functionalized Carbazoles from Indoles. AB - A novel Pd(II)-catalyzed approach for the direct synthesis of differentially substituted carbazoles from free (NH) indoles via regioselective triple successive oxidative Heck (Fujiwara-Moritani reaction) has been achieved. It is demonstrated that both electron-deficient and electron-rich alkenes could be used successively for the incorporation of two different functional groups into the product. The proposed mechanistic pathway was well supported by isolating the first and second successive oxidative Heck intermediates as well as by trapping with styrene-d3. PMID- 26161731 TI - Buchwald-Hartwig Amination of (Hetero)Aryl Tosylates Using a Well-Defined N Heterocyclic Carbene/Palladium(II) Precatalyst. AB - The cross-coupling of aryl tosylates with amines and anilines was achieved by using for the first time a Pd-NHC system based on the popular Pd-PEPPSI precatalyst platform in which the anchoring imidazol-2-ylidene ligand IPr((NMe2)2) incorporates two dimethylamino groups as backbone substituents enhancing both the electronic and steric properties of the carbene. The system optimization and its application scope are disclosed. PMID- 26161729 TI - Mechanism of phospho-ubiquitin-induced PARKIN activation. AB - The E3 ubiquitin ligase PARKIN (encoded by PARK2) and the protein kinase PINK1 (encoded by PARK6) are mutated in autosomal-recessive juvenile Parkinsonism (AR JP) and work together in the disposal of damaged mitochondria by mitophagy. PINK1 is stabilized on the outside of depolarized mitochondria and phosphorylates polyubiquitin as well as the PARKIN ubiquitin-like (Ubl) domain. These phosphorylation events lead to PARKIN recruitment to mitochondria, and activation by an unknown allosteric mechanism. Here we present the crystal structure of Pediculus humanus PARKIN in complex with Ser65-phosphorylated ubiquitin (phosphoUb), revealing the molecular basis for PARKIN recruitment and activation. The phosphoUb binding site on PARKIN comprises a conserved phosphate pocket and harbours residues mutated in patients with AR-JP. PhosphoUb binding leads to straightening of a helix in the RING1 domain, and the resulting conformational changes release the Ubl domain from the PARKIN core; this activates PARKIN. Moreover, phosphoUb-mediated Ubl release enhances Ubl phosphorylation by PINK1, leading to conformational changes within the Ubl domain and stabilization of an open, active conformation of PARKIN. We redefine the role of the Ubl domain not only as an inhibitory but also as an activating element that is restrained in inactive PARKIN and released by phosphoUb. Our work opens up new avenues to identify small-molecule PARKIN activators. PMID- 26161732 TI - Two Is Not Always Better Than One: A Critical Evaluation of Two-System Theories. AB - Over the past two decades, there has been an upsurge in theoretical frameworks alluding to the existence of two different processing systems that supposedly operate according to different rules. This article critically examines the scientific advance offered by these theories (in particular advances in the domains of reasoning, decision making, and social cognition) and questions their theoretical coherence as well as the evidence for their existence. We scrutinize the conceptual underpinnings of two-system models and explicate the assumptions underlying these models to see whether they are reasonable. We also evaluate the empirical paradigms used to validate two-system models and ponder about their explanatory strength and predictive power. Given the popularity of these models, we discuss the appeal of two-system theories and suggest potential reasons for their prevalence. We comment on the potential costs associated with these models and allude to the desired nature of potential alternatives. We conclude that two system models currently provide little scientific advance, and we encourage researchers to adopt more rigorous conceptual definitions and employ more stringent criteria for testing the empirical evidence in support for two-system theories. PMID- 26161733 TI - Educational Policy and Country Outcomes in International Cognitive Competence Studies. AB - Prior studies of studentsqqaposxx and adultsqqaposxx cognitive competence have shown large differences between nations, equivalent to a difference of 5 to 10 years of schooling. These differences seem to be relevant because studies using different research paradigms have demonstrated that population-level cognitive abilities are related to a number of important societal outcomes, including productivity, democratization, and health. In this overview of transnational differences, we document a number of positive predictors of international differences in student competence, including the amount of preschool education, student discipline, quantity of education, attendance at additional schools, early tracking, the use of centralized exams and high-stakes tests, and adult educational attainment. We found rather negative relationships for grade retention rates, age of school onset, and class size. Altogether, these results, when combined with the outcomes of earlier studies, demonstrate that international differences in cognitive competence can be explained in part by aspects of the respective countriesqqaposxx educational systems and that these differences consequently can be reduced by reform of their educational policy. This has important implications not just for closing gaps in educational achievement, but for narrowing international gaps in wealth, health, and democracy. PMID- 26161734 TI - Ten Statisticians and Their Impacts for Psychologists. AB - Although psychologists frequently use statistical procedures, they are often unaware of the statisticians most associated with these procedures. Learning more about the people will aid understanding of the techniques. In this article, I present a list of 10 prominent statisticians: David Cox, Bradley Efron, Ronald Fisher, Leo Goodman, John Nelder, Jerzy Neyman, Karl Pearson, Donald Rubin, Robert Tibshirani, and John Tukey. I then discuss their key contributions and impact for psychology, as well as some aspects of their nonacademic lives. PMID- 26161735 TI - A Role for the X Chromosome in Sex Differences in Variability in General Intelligence? AB - There is substantial evidence that males are more variable than females in general intelligence. In recent years, researchers have presented this as a reason that, although there is little, if any, mean sex difference in general intelligence, males tend to be overrepresented at both ends of its overall distribution. Part of the explanation could be the presence of genes on the X chromosome related both to syndromal disorders involving mental retardation and to population variation in general intelligence occurring normally. Genes on the X chromosome appear overrepresented among genes with known involvement in mental retardation, which is consistent with a model we developed of the population distribution of general intelligence as a mixture of two normal distributions. Using this model, we explored the expected ratios of males to females at various points in the distribution and estimated the proportion of variance in general intelligence potentially due to genes on the X chromosome. These estimates provide clues to the extent to which biologically based sex differences could be manifested in the environment as sex differences in displayed intellectual abilities. We discuss these observations in the context of sex differences in specific cognitive abilities and evolutionary theories of sexual selection. PMID- 26161736 TI - Sex Differences in Variability for Cognitive Measures: Do the Ends Justify the Genes? (Commentary on Johnson et al., 2009). AB - Theories about the origin of cognitive sex differences must address differences in three portions of ability distributions: low-tail variability, high-tail variability, and mean values. In addition, genetic theories must provide evidence that these three types of differences are (at least in large part) caused by alleles that are located on the X chromosome. It is well established that there are more mentally retarded males than females, and this disparity is attributable to genes located on the X chromosome. By contrast, there are no known "intelligence genes" that can provide a parallel explanation for differences in variability in the high ability tail of distributions. Mean differences between males and females also defy any X-linked hypothesis about average intelligence because females and males excel on different cognitive measures. Thus, we conclude that X-linked genetic explanations of cognitive sex differences can only be substantiated as a causal explanation for the excess of males diagnosed with mental retardation. PMID- 26161737 TI - Commentary on "A Role for the X Chromosome in Sex Differences in Variability in General Intelligence?" (Johnson et al., 2009). AB - Johnson et al.'s (2009) article highlights the role of X-chromosomal genes in general intelligence and draws attention to their potential role in explaining the observed greater variance for this trait in males and their excess at both extremes of the distribution. We note that this would result from a simple additive effect of X-linked intelligence genes and also discuss the potentially important contribution of recessive deleterious loci. The buffering effect of heterozygosity in females will be partly constrained by the skewing of X inactivation patterns increasing the variance of females beyond what is expected. Furthermore, escape of some X-linked genes from in-activation may also be relevant to male-female variance comparisons. We also comment on the difficulty of establishing the extent to which the X chromosome is enriched for intelligence genes and point out that their estimates of the proportion of genes influencing general intelligence that might be located on the X chromosome rely on some doubtful premises, especially concerning the likely equivalence of X-linked gene action in males and females. Finally, we discuss the increasingly compelling evidence for the accumulation of genes on the X chromosome that have selective benefit to males, including those implicated infertility and some manifestations of intelligence. PMID- 26161738 TI - Speculation to Inform and Speculation to Explore: Response to Craig et al. (2009) and Turkheimer & Halpern (2009). AB - Scientific speculation is exploration, but it can also be used to inform, particularly across disciplines. This article, a follow-up to an empirical article on the same subject, was written with both of these purposes in mind. Many researchers are interested in uncovering the genetic mechanisms underlying general intelligence, so no doubt the roles of genes on the X chromosome will one day be understood. Psychologists can contribute best to these developments by being informed about the genetic issues involved. PMID- 26161740 TI - The Effectiveness of Age-Specific Isolation Policies on Epidemics of Influenza A (H1N1) in a Large City in Central South China. AB - During the early stage of a pandemic, isolation is the most effective means of controlling transmission. However, the effectiveness of age-specific isolation policies is not clear; especially little information is available concerning their effectiveness in China. Epidemiological and serological survey data in the city of Changsha were employed to estimate key model parameters. The average infectious period (date of recovery-date of symptom onset) of influenza A (H1N1) was 5.2 days. Of all infected persons, 45.93% were asymptomatic. The basic reproduction number of the influenza A (H1N1) pandemic was 1.82. Based on the natural history of influenza A (H1N1), we built an extended susceptible-exposed infectious/asymptomatic-removed model, taking age groups: 0-5, 6-14, 15-24, 25 59, and >=60 years into consideration for isolation. Without interventions, the total attack rates (TARs) in each age group were 42.73%, 41.95%, 20.51%, 45.03%, and 37.49%, respectively. Although the isolation of 25-59 years-old persons was the most effective, the TAR of individuals of aged 0-5 and 6-14 could not be reduced. Paradoxically, isolating individuals >=60 year olds was not predicted to be an effective way of reducing the TAR in this group but isolating the age-group 25-59 did, which implies inter-age-group transmission from the latter to the former is significant. Isolating multiple age groups increased effectiveness. The most effective combined isolation target groups were of 6-14 + 25-59 year olds, 6 14 + 15-24 + 25-59 year olds, and 0-5 + 6-14 + 25-59 + >=60 year olds. The last of these isolation schemas reduced the TAR of the total population from 39.64% to 0.006%, which was exceptionally close to the effectiveness of isolating all five age groups (TAR = 0.004%). PMID- 26161741 TI - Effect of Probiotics on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials. AB - BACKGROUND: Previous clinical trials indicate that probiotic consumption may improve blood glucose control, however, results from randomized trials on glycemic control have been inconsistent. OBJECTIVE: To investigate the effects of probiotics on glycemic control in a systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: PubMed, Embase, Cochrane Library, and Clinicaltrial.gov through October 2014. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using a random-effects model and expressed as mean differences (MD) with 95% CI. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2). RESULTS: Seventeen randomized controlled trials were included, in which 17 fasting blood glucose (n = 1105), 11 fasting plasma insulin (n = 788), 8 homeostasis model assessment of insulin resistance (n = 635) comparisons were reported. Probiotic consumption, compared with placebo, significantly reduced fasting glucose (MD = -0.31 mmol/L; 95% CI 0.56, 0.06; p = 0.02), fasting plasma insulin (MD = -1.29 MUU/mL; 95% CI -2.17, -0.41; p = 0.004), and HOMA-IR (MD = 0.48; 95% CI -0.83, -0.13; p = 0.007). CONCLUSIONS: Probiotic consumption may improve glycemic control modestly. Modification of gut microbiota by probiotic supplementation may be a method for preventing and control hyperglycemia in clinical practice. PMID- 26161742 TI - Phylogeny and New Classification of Hydrothermal Vent and Seep Shrimps of the Family Alvinocarididae (Decapoda). AB - The paper addresses the phylogeny and classification of the hydrothermal vent shrimp family Alvinocarididae. Two morphological cladistic analyses were carried out, which use all 31 recognized species of Alvinocarididae as terminal taxa. As outgroups, two species were included, both representing major caridean clades: Acanthephyra purpurea (Acanthephyridae) and Alpheus echiurophilus (Alpheidae). For additional support of the clades we utilised available data on mitochondrial Cytochrome c Oxidase I gene (CO1) and 16S ribosomal markers. Both morphological and molecular methods resulted in similar tree topologies and nearly identical clades. We consider these clades as evolutionary units and thus erect two new subfamilies: Rimicaridinae (Alvinocaridinides, Manuscaris, Opaepele, Shinkaicaris, Rimicaris), Alvinocaridinae (Alvinocaris), whilst recognising Mirocaridinae (with genera Mirocaris and Nautilocaris) at subfamily level. One genus, Keldyshicaris could not be assigned to any subfamily and is thus left as incertae sedis. The monophyly of Alvinocardinae was supported by morphological data, but not supported by molecular data (two analyses); the monophyly of all subfamilies was supported both by morphological and molecular data. Chorocaris is herein synonymized with Rimicaris, whilst Opaepele vavilovi is herein transferred to a new genus Keldyshicaris. Morphological trends within Alvinocarididae are discussed and short biogeographical remarks are given. We provide emended diagnoses for all subfamilies and genera along with keys to all recognized species. PMID- 26161743 TI - Chicken Caecal Microbiome Modifications Induced by Campylobacter jejuni Colonization and by a Non-Antibiotic Feed Additive. AB - Campylobacter jejuni is an important zoonotic foodborne pathogen causing acute gastroenteritis in humans. Chickens are often colonized at very high numbers by C. jejuni, up to 10(9) CFU per gram of caecal content, with no detrimental effects on their health. Farm control strategies are being developed to lower the C. jejuni contamination of chicken food products in an effort to reduce human campylobacteriosis incidence. It is believed that intestinal microbiome composition may affect gut colonization by such undesirable bacteria but, although the chicken microbiome is being increasingly characterized, information is lacking on the factors affecting its modulation, especially by foodborne pathogens. This study monitored the effects of C. jejuni chicken caecal colonization on the chicken microbiome in healthy chickens. It also evaluated the capacity of a feed additive to affect caecal bacterial populations and to lower C. jejuni colonization. From day-0, chickens received or not a microencapsulated feed additive and were inoculated or not with C. jejuni at 14 days of age. Fresh caecal content was harvested at 35 days of age. The caecal microbiome was characterized by real time quantitative PCR and Ion Torrent sequencing. We observed that the feed additive lowered C. jejuni caecal count by 0.7 log (p<0.05). Alpha-diversity of the caecal microbiome was not affected by C. jejuni colonization or by the feed additive. C. jejuni colonization modified the caecal beta-diversity while the feed additive did not. We observed that C. jejuni colonization was associated with an increase of Bifidobacterium and affected Clostridia and Mollicutes relative abundances. The feed additive was associated with a lower Streptococcus relative abundance. The caecal microbiome remained relatively unchanged despite high C. jejuni colonization. The feed additive was efficient in lowering C. jejuni colonization while not disturbing the caecal microbiome. PMID- 26161744 TI - The Role of the Two-Component System BaeSR in Disposing Chemicals through Regulating Transporter Systems in Acinetobacter baumannii. AB - Bacterial two-component regulatory systems (TCSs) facilitate changes in gene expression in response to environmental stimuli. TCS BaeR regulons influence tigecycline susceptibility in Acinetobacter baumannii through positively regulating the pump genes adeA and adeB. In this study, we demonstrate that an additional two transport systems, AdeIJK and MacAB-TolC, are also regulated by BaeSR. In the wild type and clinical tigecycline-resistant A. baumannii strains, gene expression of AdeIJK and MacAB-TolC increased after tigecycline induction, implicating their importance to tigecycline resistance in addition to AdeABC. Phenotypic microarray results showed that A. baumannii is vulnerable to certain chemicals, especially tannic acid, after deleting baeR, which was confirmed using the spot assay. The wild-type strain of A. baumannii also exhibited 1.6-fold and 4.4-fold increase in gene expression of adeJ and macB in the medium with 100 MUg/mL tannic acid, but the increase was fully inhibited by baeR deletion. An electrophoretic motility shift assay based on an interaction between His-BaeR and the adeA, adeI and macA promoter regions did not demonstrate direct binding. In conclusion, A. baumannii can use the TCS BaeSR in disposing chemicals, such as tannic acid and tigecycline, through regulating the efflux pumps. PMID- 26161745 TI - Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira. AB - NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden. PMID- 26161746 TI - IRF6 Is Involved in the Regulation of Cell Proliferation and Transformation in MCF10A Cells Downstream of Notch Signaling. AB - IRF6, a member of Interferon Regulatory Factors (IRF) family, is involved in orofacial and epidermal development. In breast cancer cell lines ectopic expression of IRF6 reduces cell numbers suggesting a role as negative regulator of cell cycle. IRF6 is a direct target of canonical Notch signaling in keratinocyte differentiation. Notch is involved in luminal cell fate determination and stem cell regulation in the normal breast and is implicated as an oncogene in breast cancer. Notch activation is sufficient to induce proliferation and transformation in non-tumorigenic breast epithelial cell line, MCF10A. DeltaNp63, which is downregulated by Notch activation in the breast, regulates IRF6 expression in keratinocytes. In this report, we investigate Notch IRF6 and DeltaNp63-IRF6 interactions in MCF10A and MDA MB 231 cells. We observed that in these cells, IRF6 expression is partially regulated by canonical Notch signaling and DeltaNp63 downregulation. Furthermore, we demonstrate that IRF6 abrogation impairs Notch-induced proliferation and transformation in MCF10A cells. Thus, we confirm the previous findings by showing a tissue independent regulation of IRF6 by Notch signaling, and extend them by proposing a context dependent role for IRF6, which acts as a positive regulator of proliferation and transformation in MCF10A cells downstream of Notch signaling. PMID- 26161747 TI - Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging. AB - Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy. PMID- 26161749 TI - Helping Doctors and Patients Make Sense of Health Statistics. AB - Many doctors, patients, journalists, and politicians alike do not understand what health statistics mean or draw wrong conclusions without noticing. Collective statistical illiteracy refers to the widespread inability to understand the meaning of numbers. For instance, many citizens are unaware that higher survival rates with cancer screening do not imply longer life, or that the statement that mammography screening reduces the risk of dying from breast cancer by 25% in fact means that 1 less woman out of 1,000 will die of the disease. We provide evidence that statistical illiteracy (a) is common to patients, journalists, and physicians; (b) is created by nontransparent framing of information that is sometimes an unintentional result of lack of understanding but can also be a result of intentional efforts to manipulate or persuade people; and (c) can have serious consequences for health. The causes of statistical illiteracy should not be attributed to cognitive biases alone, but to the emotional nature of the doctor-patient relationship and conflicts of interest in the healthcare system. The classic doctor-patient relation is based on (the physician's) paternalism and (the patient's) trust in authority, which make statistical literacy seem unnecessary; so does the traditional combination of determinism (physicians who seek causes, not chances) and the illusion of certainty (patients who seek certainty when there is none). We show that information pamphlets, Web sites, leaflets distributed to doctors by the pharmaceutical industry, and even medical journals often report evidence in nontransparent forms that suggest big benefits of featured interventions and small harms. Without understanding the numbers involved, the public is susceptible to political and commercial manipulation of their anxieties and hopes, which undermines the goals of informed consent and shared decision making. What can be done? We discuss the importance of teaching statistical thinking and transparent representations in primary and secondary education as well as in medical school. Yet this requires familiarizing children early on with the concept of probability and teaching statistical literacy as the art of solving real-world problems rather than applying formulas to toy problems about coins and dice. A major precondition for statistical literacy is transparent risk communication. We recommend using frequency statements instead of single-event probabilities, absolute risks instead of relative risks, mortality rates instead of survival rates, and natural frequencies instead of conditional probabilities. Psychological research on transparent visual and numerical forms of risk communication, as well as training of physicians in their use, is called for. Statistical literacy is a necessary precondition for an educated citizenship in a technological democracy. Understanding risks and asking critical questions can also shape the emotional climate in a society so that hopes and anxieties are no longer as easily manipulated from outside and citizens can develop a better-informed and more relaxed attitude toward their health. PMID- 26161750 TI - Statistical Literacy: A Prerequisite for Evidence-Based Medicine. PMID- 26161748 TI - The LMO2 -25 Region Harbours GATA2-Dependent Myeloid Enhancer and RUNX-Dependent T-Lymphoid Repressor Activity. AB - Lim domain only 2 (LMO2) is a transcriptional co-factor required for angiogenesis and the specification of haematopoietic cells during development. LMO2 is widely expressed within haematopoiesis with the exception of T-cells. Failure to downregulate LMO2 during T-cell maturation leads to leukaemia, thus underlining the critical nature of context-dependent regulation of LMO2 expression. We previously identified a distal regulatory element of LMO2 (element -25) that cooperates with the proximal promoter in directing haematopoietic expression. Here we dissected the functional activity of element -25 and showed it to consist of two modules that conferred independent and cell-type specific activities: a 3' myeloid enhancer and a 5' T-cell repressor. The myeloid enhancer was bound by GATA2 in progenitors and its activity depended on a highly conserved GATA motif, whereas the T-cell repressor moiety of element -25 was bound by the Core Binding Factor in T-cells and its repressive activity depended on a highly conserved RUNT motif. Since the myeloid enhancer and nearby downstream region is recurrently involved in oncogenic translocations, our data suggest that the -25 enhancer region provides an open chromatin environment prone to translocations, which in turn cause aberrant LMO2 expression in T-cells due to the removal of the adjacent T-cell repressor. PMID- 26161751 TI - Correlates of Untreated Hypercholesterolemia in Older Adults: A Community-Based Household Survey in China. AB - Hypercholesterolemia is common in older adults and less treated, but little is known about correlates of untreated hypercholesterolemia. Using a standard interview method we examined a random sample of 7,572 participants aged >=60 years in a community-based household survey across 7 provinces of China during 2007-2012, and documented 328 cases of hypercholesterolemia from self-reported doctor diagnosis. Compared to participants with normal cholesterol, older adults with hypercholesterolemia had higher socioeconomic position and larger body mass index. In patients with hypercholesterolemia, 209 were not treated using lipid lowering medications (63.7%, 95% confidence interval (CI) 58.5%-68.9%). Untreated hypercholesterolemia was significantly associated with female sex (adjusted odds ratio 2.13, 95%CI 1.17-3.89), current smoking (3.48, 1.44-8.44), heavy alcohol drinking (3.13,1.11-8.84), chronic bronchitis (2.37,1.14-4.90) and high level of meat consumptions (2.85,1.22-6.65). Although having coronary heart disease exposed participants for treatment, half of participants with coronary heart disease did not receive lipid-lowering medications. Among hypercholesterolemia participants with stroke, hypertension or diabetes, more than half of them did not receive lipid-lowering medications. The high proportion of untreated hypercholesterolemia in older, high-risk Chinese adults needs to be mitigated through multi-faceted primary and secondary prevention strategies to increase population opportunities of treating hypercholesterolemia. PMID- 26161752 TI - Transcriptome-Based Identification of Highly Similar Odorant-Binding Proteins among Neotropical Stink Bugs and Their Egg Parasitoid. AB - Olfaction plays a fundamental role in insect survival through resource location and intra and interspecific communications. We used RNA-Seq to analyze transcriptomes for odorant-binding proteins (OBPs) from major stink bug pest species in Brazil, Euschistus heros, Chinavia ubica, and Dichelops melacanthus, and from their egg parasitoid, Telenomus podisi. We identified 23 OBPs in E. heros, 25 OBPs in C. ubica, 9 OBPs in D. melacanthus, and 7 OBPs in T. podisi. The deduced amino acid sequences of the full-length OBPs had low intraspecific similarity, but very high similarity between two pairs of OBPs from E. heros and C. ubica (76.4 and 84.0%) and between two pairs of OBPs from the parasitoid and its preferred host E. heros (82.4 and 88.5%), confirmed by a high similarity of their predicted tertiary structures. The similar pairs of OBPs from E. heros and C. ubica may suggest that they have derived from a common ancestor, and retain the same biological function to bind a ligand perceived or produced in both species. The T. podisi OBPs similar to E. heros were not orthologous to any known hymenopteran OBPs, and may have evolved independently and converged to the host OBPs, providing a possible basis for the host location of T. podisi using E. heros semiochemical cues. PMID- 26161755 TI - A Conversation With AAOS President David D. Teuscher, MD. PMID- 26161753 TI - Managing the Sick Child in the Era of Declining Malaria Transmission: Development of ALMANACH, an Electronic Algorithm for Appropriate Use of Antimicrobials. AB - OBJECTIVE: To review the available knowledge on epidemiology and diagnoses of acute infections in children aged 2 to 59 months in primary care setting and develop an electronic algorithm for the Integrated Management of Childhood Illness to reach optimal clinical outcome and rational use of medicines. METHODS: A structured literature review in Medline, Embase and the Cochrane Database of Systematic Review (CDRS) looked for available estimations of diseases prevalence in outpatients aged 2-59 months, and for available evidence on i) accuracy of clinical predictors, and ii) performance of point-of-care tests for targeted diseases. A new algorithm for the management of childhood illness (ALMANACH) was designed based on evidence retrieved and results of a study on etiologies of fever in Tanzanian children outpatients. FINDINGS: The major changes in ALMANACH compared to IMCI (2008 version) are the following: i) assessment of 10 danger signs, ii) classification of non-severe children into febrile and non-febrile illness, the latter receiving no antibiotics, iii) classification of pneumonia based on a respiratory rate threshold of 50 assessed twice for febrile children 12-59 months; iv) malaria rapid diagnostic test performed for all febrile children. In the absence of identified source of fever at the end of the assessment, v) urine dipstick performed for febrile children <2 years to consider urinary tract infection, vi) classification of 'possible typhoid' for febrile children >2 years with abdominal tenderness; and lastly vii) classification of 'likely viral infection' in case of negative results. CONCLUSION: This smartphone run algorithm based on new evidence and two point-of-care tests should improve the quality of care of <5 year children and lead to more rational use of antimicrobials. PMID- 26161756 TI - Closed Reduction of Subacute Patellar Dislocation Using Saline Joint Insufflation: A Technical Trick. AB - Patellar dislocations often spontaneously reduce or are reduced easily by experienced professionals. However, some dislocations can prove difficult to reduce and may require sedation or operative management. Our case report suggests an alternative method to facilitate reduction of patellar dislocations. Our technical trick involves insufflation of the knee joint with sterile normal saline, resulting in improved clearance of the patella over the femoral condyles. This low-risk technique can aid in the reduction of a dislocated patella and save the patient from unnecessary sedation or a surgical operation. PMID- 26161754 TI - Immediate Epileptogenesis after Kainate-Induced Status Epilepticus in C57BL/6J Mice: Evidence from Long Term Continuous Video-EEG Telemetry. AB - The C57BL/6J mouse as a model of seizure/epilepsy is challenging due to high mortality and huge variability in response to kainate. We have recently demonstrated that repeated administration of a low dose of kainate by intraperitoneal route can induce severe status epilepticus (SE) with 94% survival rate. In the present study, based on continuous video-EEG recording for 4-18 weeks from epidurally implanted electrodes on the cortex, we demonstrate that this method also induces immediate epileptogenesis (<1-5 days post-SE). This finding was based on identification of two types of spontaneous recurrent seizures; behavioral convulsive seizures (CS) and electrographic nonconvulsive seizures (NCS). The identification of the spontaneous CS, stage 3-5 types, was based on the behaviors (video) that were associated with the EEG characteristics (stage 3-5 epileptiform spikes), the power spectrum, and the activity counts. The electrographic NCS identification was based on the stage 1-2 epileptiform spike clusters on the EEG and their associated power spectrum. Severe SE induced immediate epileptogenesis in all the mice. The maximum numbers of spontaneous CS were observed during the first 4-6 weeks of the SE and they decreased thereafter. Mild SE also induced immediate epileptogenesis in some mice but the CS were less frequent. In both the severe and the mild SE groups, the spontaneous electrographic NCS persisted throughout the 18 weeks observation period, and therefore this could serve as a chronic model for complex seizures. However, unlike rat kainate models, the C57BL/6J mouse kainate model is a unique regressive CS model of epilepsy. Further studies are required to understand the mechanism of recovery from spontaneous CS in this model, which could reveal novel therapeutic targets for epilepsy. PMID- 26161757 TI - Fish Oil and Osteoarthritis: Current Evidence. AB - According to the 2005 US census, osteoarthritis (OA) was the leading cause of disability in the United States, affecting more than 50 million people. Current treatments are targeted at reducing symptoms of the inflammatory reaction that occurs after destruction of essential joint cartilage. However, these treatments do not prevent significant pain and activity restriction. We reviewed the literature to address claims that fish oil supplementation can prevent or decrease severity of OA. Our extensive search of databases covered all relevant terms related to omega-3-containing supplements and their effects on OA. We hypothesized there would be insufficient clinical studies to justify recommending supplementation to patients.Laboratory studies have shown that eicosapentaenoic acid and docosahexaenoic acid reduce proinflammatory mediators and increase joint lubrication in vitro. In addition, canine trials have shown clinically significant reductions in various symptom parameters. Results of human clinical trials have not been consistently significant. Well-designed clinical trials are needed to substantiate or refute the potential benefit of fish oils in OA treatment. Long-term studies are needed to assess the possibility of prevention. In addition, standardization of the fish oil industry is needed for consistency of therapy. PMID- 26161758 TI - The Role of Vitamin C in Orthopedic Trauma and Bone Health. AB - Vitamin C is an essential micronutrient with an adult daily recommended intake of 75 mg for women and 90 mg for men. Smokers should consume an additional 35 mg per day because of the increased oxidative stresses from cigarette smoke. Observational data support the hypothesis that high dietary intake and supplementation with vitamin C may reduce the risk of hip fractures in postmenopausal women. Results of 2 high-quality trials support use of vitamin C 500 mg daily for 50 days as prophylaxis against complex regional pain syndrome after wrist fracture treated conservatively and operatively. Observational evidence exists for similar treatment after foot and ankle surgery. The role of vitamin C in preventing osteoarthritis has tremendous potential, though results in animal and human studies are controversial. The heterogeneous results and the lack of prospective trials preclude any recommendation at this time. PMID- 26161759 TI - Reducing Postoperative Fracture Displacement After Locked Plating of Proximal Humerus Fractures: Current Concepts. AB - The incidence of proximal humerus fractures in the elderly has been rising. Concomitantly, operative fixation with use of locking plates has been increasing. Postoperative complications of locking plate fixation, particularly in the setting of osteoporotic bone, include screw penetration of the articular surface, progressive fracture displacement, and avascular necrosis. Intraoperative techniques to enhance the fixation construct and reduce complications include use of rotator cuff sutures, bone void fillers (fibular strut allograft, cancellous allograft, autograft, bone cement), appropriate placement of divergent and shorter locking screws, and medial calcar reduction and support. More recent clinical and biomechanical studies suggest that use of these strategies may reduce complications after locked plating of osteoporotic proximal humerus fractures. Furthermore, a multidisciplinary approach to the evaluation and treatment of osteoporosis may be beneficial in these patients. PMID- 26161760 TI - Total Hip Arthroplasty for Posttraumatic Osteoarthritis of the Hip Fares Worse Than THA for Primary Osteoarthritis. AB - We conducted a study to evaluate differences between patients who had total hip arthroplasty (THA) for posttraumatic osteoarthritis (OA) and patients who had THA for primary OA. Using a prospective database, we followed 3844 patients who had THA for OA. Those who had THA for secondary causes of hip OA, developmental hip dysplasia, or inflammatory processes were excluded. Of the remaining 1199 patients, 62 (63 fractures) had THA for posttraumatic OA after previous acetabular or proximal femur fracture fixation, and 1137 had THA for primary OA and served as the control group. In the posttraumatic OA group, mean time between fracture repair and conversion to THA was 74 months. Compared with the control patients, the posttrauma patients lost more blood, were transfused more units of blood, had longer operating room times, and had more complications (all Ps < .001). Posttrauma patients had a mean follow-up of 4.44 years and a mean postoperative modified Harris Hip Score of 81.3 at latest follow-up. Of these patients, 12.5% required revision a mean of 3.5 years after initial arthroplasty. THA in patients with posttraumatic hip OA after an acetabular or proximal femur fracture is a longer and more complicated procedure with a higher rate of early failure. PMID- 26161761 TI - Revision Rotator Cuff Reconstruction for Large Tears With Retraction: A Novel Technique Using Autogenous Tendon and Autologous Marrow. AB - Revision rotator cuff reconstruction for large tears with retraction results in a high rate of recurrent cuff tearing. To try to obtain more consistent results, I conducted a study of a technique that addresses the potential factors involved. Ten patients (7 men, 3 women) were enrolled. Mean age was 58 years. Mean follow up was 24 months. Mean time between primary and revision cuff surgery was 36 months. The cardinal inclusion criterion was a symptomatic, full-thickness rotator cuff tear with at least 3 cm of retraction in a shoulder that previously underwent rotator cuff repair. Ultrasound was used for postoperative radiographic assessment of cuff integrity. Validated Constant, American Shoulder and Elbow Surgeons (ASES), and University of California Los Angeles (UCLA) shoulder scoring systems were used. Surgical technique included mini-open incision, adequate debridement and mobilization of remaining cuff, reconstitution of cuff defect with autogenous biceps tendon incubated in concentrated autologous bone marrow, and sewing under zero tissue tension. Constant, ASES, and UCLA scores improved significantly (standard error at .001). Ultrasound revealed 0% incidence of full thickness rotator cuff retearing. In patients with large recurrent retracted rotator cuff tears the technique presented in the current study consistently yields satisfactory clinical results and promotes rotator cuff tissue healing without full-thickness retearing. PMID- 26161762 TI - ICD-10 Race to the Finish: 8 High Priorities in the 11th Hour. PMID- 26161763 TI - Image-Based Techniques for Percutaneous Iliosacral Screw Start-Site Localization. AB - Despite the routine use of iliosacral screws for the treatment of a variety of pelvic fractures, the technique is demanding, and complications are well described. This article describes a novel image-based technique for accurately identifying and reproducing the appropriate placement of iliosacral screws. Using the stab-incision technique presented here allows for more accurate landmark identification and safer placement of implants. PMID- 26161764 TI - American Academy of Orthopaedic Surgeons Disclosure Policy Fails to Accurately Inform Its Members of Potential Conflicts of Interest. AB - The American Academy of Orthopaedic Surgeons (AAOS) disclosure policy is designed to ensure that members involved in education or policy development remain free of outside influence. Although mandatory for these members, it is voluntary for the rest of the AAOS membership. To determine surgeon compliance with disclosure policy, we conducted a study in which we compared surgeon-consultants' disclosures as posted on 6 major orthopedic companies' websites in 2011 with those surgeons' disclosures as listed in AAOS disclosure program records. We found that 549 AAOS members were identified by at least 1 company as having received consulting payments. Overall, 44% of AAOS members did not comply with disclosure policy, or their information was not available on the AAOS website (range, 37%-61%). This study demonstrated that AAOS's policy of mandatory disclosure for select members and voluntary disclosure for all other members is ineffective. The AAOS disclosure program and the potential consequences of noncompliance need to be reevaluated by the organization if it wants its program to succeed. PMID- 26161765 TI - Comparison of Outcomes and Costs of Tension-Band and Locking-Plate Osteosynthesis in Transverse Olecranon Fractures: A Matched-Cohort Study. AB - To determine if there are significant differences in outcomes and costs between tension-band and locking-plate fixation of transverse olecranon fractures in adults, we retrospectively compared functional outcomes, complications, and costs in 2 cohorts of displaced transverse olecranon fractures. These cohorts (10 patients each) were matched on age and length of follow-up. There were no significant differences between the groups in range of motion, functional scores, or arthrosis. There were no infections or nonunions in either group. There was no significant difference in rate of implant removal or symptomatic implants, though a trend was found toward a higher rate of both with tension bands. Operative time was significantly (P = .025) less for tension-band than locking-plate fixation (55 vs 85 minutes). In the tension-band group, charges were significantly less for implant, index procedure, and overall operative charges including reoperations ($6598.36 vs $14,333.46; P = .001). If all tension bands and no locking plates had been removed, tension-band fixation still would have cost significantly less ($7307.31 vs $14,160.26; P = .0005). PMID- 26161766 TI - Isolating Suture Slippage During Cadaveric Testing of Knotless Anchors. AB - We evaluated a testing method designed to isolate and analyze the effectiveness of different suture-retention mechanisms in knotless suture anchors used for rotator cuff repairs. Six knotless PushLock implants (Arthrex) with a suture retention mechanism dependent on a press-fit of suture between the anchor's outer diameter and surrounding bone were compared with 6 ReelX STT devices (Stryker) reliant on an intrinsic suture-locking mechanism. Suture slippage beyond minimal clinical failure thresholds, as well as ultimate failure load, were determined with a novel testing fixture that isolated suture slippage. Suture slippage was isolated from anchor-bone disengagement. Each PushLock exhibited suture slippage of more than 3 mm, and each ReelX exhibited slippage of less than 3 mm. The PushLock implants also exhibited significantly (P < .05) more interval and maximum slippage; 5 of these 6 implants failed via complete suture slippage before dynamic testing could be completed. All ReelX devices survived dynamic testing and ultimately failed via suture breakage. This novel axial load biomechanical testing technique isolated suture slippage in 2 uniquely designed knotless anchors. The press-fit PushLock implant was prone to slippage failure, whereas the ReelX device with its internal suture-locking mechanism exhibited minimal slippage. PMID- 26161767 TI - Risk Factors for Thromboembolic Events After Surgery for Ankle Fractures. AB - We conducted a retrospective national-cohort study to determine the incidence of and independent risk factors for venous thromboembolic events (VTEs) after open reduction and internal fixation (ORIF) of ankle fractures. Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified patients who underwent ORIF for ankle fracture between 2005 and 2012. VTE was defined as the occurrence of a deep vein thrombosis or a pulmonary embolism within the first 30 postoperative days. Of the 4412 ankle fracture patients who met the inclusion criteria, 33 (0.8%) had a VTE. Multivariate analysis revealed that body mass index (BMI) of 30 to 35 kg/m2 (odds ratio [OR], 4.77; 95% confidence interval [CI], 1.05-21.72; P = .044), BMI of 35 kg/m2 or higher (OR, 4.71; 95% CI, 1.03-21.68; P = .046), heart disease (OR, 3.28; 95% CI, 1.20-8.97; P = .020), and dependent functional status (OR, 2.59; 95% CI, 1.11-6.04; P = .028) were independently associated with occurrence of VTE after ankle fracture ORIF. Patients with higher BMI and patients with heart disease or dependent functional status may be considered for VTE prophylaxis. PMID- 26161768 TI - Evaluation of 3 Fixation Devices for Tibial-Sided Anterior Cruciate Ligament Graft Backup Fixation. AB - We conducted a study to biomechanically evaluate 3 methods of tibial-sided fixation for anterior cruciate ligament reconstruction: fully threaded interference screw only, interference screw backed with 4.75-mm SwiveLock anchor, and fully threaded bio-interference screw backed with 4.5-mm bicortical screw (all Arthrex). Thirty skeletally mature porcine tibiae were used. The first group was prepared by graft fixation within the tibial tunnel using only an interference screw. The second and third groups included an interference screw with 2 types of secondary fixation: 4.5-mm bicortical post and SwiveLock anchor. Mechanical testing consisted of 500 cycles between 50 and 250 N at 1 Hz, followed by a pull to failure conducted at 20 mm per minute. Ultimate load-to-failure testing demonstrated the largest mean (SD) load tolerated in the post/washer group, 1148 (186) N, versus the SwiveLock group, 1007 (176) N, and the screw-only group, 778 (139) N. There was no statistical difference between the 2 backup fixation groups. Use of a SwiveLock anchor as backup fixation at the tibial side in soft-tissue anterior cruciate ligament reconstruction is a safe, effective alternative to a bicortical post and provides statistically equivalent pullout strength with unlikely requirement for future hardware removal. PMID- 26161769 TI - Enoxaparin and Warfarin for Venous Thromboembolism Prophylaxis in Total Hip Arthroplasty: To Bridge or Not to Bridge? AB - Anticoagulation bridges consisting of subcutaneous enoxaparin combined with oral dosed warfarin are commonly used in orthopedic procedures as chemoprophylaxis against thromboembolic disease. For some patients, these bridges result in complications. One hundred twenty-one patients were evaluated after primary total hip arthroplasty (THA) between 2008 and 2009. Sixty-three patients were given bridged therapy after THA, and 58 were given warfarin only. The 2 groups were statistically matched on various comorbidities. Outcomes of interest were number of days to dry wound and length of hospital stay. Wounds of patients given anticoagulation bridges took longer to heal than wounds of patients given warfarin only (odds ratio, 2.39; P < .05). In addition, patients given anticoagulation bridges had longer hospital stays (odds ratio, 1.27; P < .05). Compared with warfarin-only therapy after THA, use of warfarin bridged with enoxaparin increased the risk for prolonged wound healing and subsequent infection. In addition, bridged therapy cost $2000 more per patient than warfarin only therapy. Further studies should examine the risks and benefits of these bridges in reducing thromboembolic disease. PMID- 26161770 TI - Supinator Cyst in a Young Female Softball Player Successfully Treated With Aspiration. AB - Ganglion cysts around the elbow joint are rare, with fewer than 25 citations in the English-language literature, most of them case reports. Among the many causes of elbow pain, cysts are primarily a diagnosis that depends on advanced imaging. When an elbow ganglion or perineural cyst is symptomatic, treatment has ranged from nonoperative to surgical intervention. Our case is unique because it is the first documented ultrasound-guided aspiration and cortisone injection that successfully alleviated a patient's symptoms. The procedures and outcomes of minimally invasive ultrasound-guided aspiration and steroid injections have not been described for cysts around the elbow. PMID- 26161771 TI - Septic Arthritis and Osteomyelitis Caused by Pasteurella multocida. AB - This report presents a case of progressive septic arthritis and osteomyelitis caused by a rare pathogen, Pasteurella multocida, thought to be provoked by the use of systemic corticosteroids. Despite initial improvement after antibiotics and surgical procedure, the patient returned with new, associated symptoms 1 month later. This concurrent set of circumstances leading to a life-threatening condition has not been reported, to the best of our knowledge. Physicians aware of such a case will be better prepared to diagnose, treat, and educate their patients. Additionally, the diagnostic challenge presented by this case report emphasizes the need for vigilance and thoroughness in obtaining histories from patients presenting with seemingly benign complaints, especially in vulnerable populations, such as infants, pregnant women, and immunocompromised adults. PMID- 26161772 TI - Madelung Deformity and Extensor Tendon Rupture. AB - Extensor tendon rupture in chronic Madelung deformity, as a result of tendon attrition on the dislocated distal ulna, is a rare occurrence. It is, however, seen more often in rheumatoid arthritis. There are few case reports in the English-language literature on this issue. We report a case of multiple tendon ruptures in a previously undiagnosed Madelung deformity. PMID- 26161773 TI - Orthopedic Resident Education and Patient Safety. PMID- 26161774 TI - Graduate Medical Education-A System in Evolution. PMID- 26161775 TI - Identification of Genetic Defects in 33 Probands with Stargardt Disease by WES Based Bioinformatics Gene Panel Analysis. AB - Stargardt disease (STGD) is the most common hereditary macular degeneration in juveniles, with loss of central vision occurring in the first or second decade of life. The aim of this study is to identify the genetic defects in 33 probands with Stargardt disease. Clinical data and genomic DNA were collected from 33 probands from unrelated families with STGD. Variants in coding genes were initially screened by whole exome sequencing. Candidate variants were selected from all known genes associated with hereditary retinal dystrophy and then confirmed by Sanger sequencing. Putative pathogenic variants were further validated in available family members and controls. Potential pathogenic mutations were identified in 19 of the 33 probands (57.6%). These mutations were all present in ABCA4, but not in the other four STGD-associated genes or in genes responsible for other retinal dystrophies. Of the 19 probands, ABCA4 mutations were homozygous in one proband and compound heterozygous in 18 probands, involving 28 variants (13 novel and 15 known). Analysis of normal controls and available family members in 12 of the 19 families further support the pathogenicity of these variants. Clinical manifestation of all probands met the diagnostic criteria of STGD. This study provides an overview of a genetic basis for STGD in Chinese patients. Mutations in ABCA4 are the most common cause of STGD in this cohort. Genetic defects in approximately 42.4% of STGD patients await identification in future studies. PMID- 26161776 TI - The Origin and Evolution of Baeyer-Villiger Monooxygenases (BVMOs): An Ancestral Family of Flavin Monooxygenases. AB - The Baeyer-Villiger Monooxygenases (BVMOs) are enzymes belonging to the "Class B" of flavin monooxygenases and are capable of performing exquisite selective oxidations. These enzymes have been studied from a biotechnological perspective, but their physiological substrates and functional roles are widely unknown. Here, we investigated the origin, taxonomic distribution and evolutionary history of the BVMO genes. By using in silico approaches, 98 BVMO encoding genes were detected in the three domains of life: Archaea, Bacteria and Eukarya. We found evidence for the presence of these genes in Metazoa (Hydra vulgaris, Oikopleura dioica and Adineta vaga) and Haptophyta (Emiliania huxleyi) for the first time. Furthermore, a search for other "Class B" monooxygenases (flavoprotein monooxygenases--FMOs--and N-hydroxylating monooxygenases--NMOs) was conducted. These sequences were also found in the three domains of life. Phylogenetic analyses of all "Class B" monooxygenases revealed that NMOs and BVMOs are monophyletic, whereas FMOs form a paraphyletic group. Based on these results, we propose that BVMO genes were already present in the last universal common ancestor (LUCA) and their current taxonomic distribution is the result of differential duplication and loss of paralogous genes. PMID- 26161777 TI - Seasonal Variation in Population Abundance and Chytrid Infection in Stream Dwelling Frogs of the Brazilian Atlantic Forest. AB - Enigmatic amphibian declines were first reported in southern and southeastern Brazil in the late 1980s and included several species of stream-dwelling anurans (families Hylodidae and Cycloramphidae). At that time, we were unaware of the amphibian-killing fungus Batrachochytrium dendrobatidis (Bd); therefore, pollution, habitat loss, fragmentation and unusual climatic events were hypothesized as primary causes of these declines. We now know that multiple lineages of Bd have infected amphibians of the Brazilian Atlantic forest for over a century, yet declines have not been associated specifically with Bd outbreaks. Because stream-dwelling anurans occupy an environmental hotspot ideal for disease transmission, we investigated temporal variation in population and infection dynamics of three stream-adapted species (Hylodes asper, H. phyllodes, and Cycloramphus boraceiensis) on the northern coast of Sao Paulo state, Brazil. We surveyed standardized transects along streams for four years, and show that fluctuations in the number of frogs correlate with specific climatic variables that also increase the likelihood of Bd infections. In addition, we found that Bd infection probability in C. boraceiensis, a nocturnal species, was significantly higher than in Hylodes spp., which are diurnal, suggesting that the nocturnal activity may either facilitate Bd zoospore transmission or increase susceptibility of hosts. Our findings indicate that, despite long-term persistence of Bd in Brazil, some hosts persist with seasonally variable infections, and thus future persistence in the face of climate change will depend on the relative effect of those changes on frog recruitment and pathogen proliferation. PMID- 26161780 TI - Stokes' Second Problem for a Micropolar Fluid with Slip. AB - In this paper is presented the model of an incompressible micropolar fluid flow with slip using the initial and boundary conditions when the wall velocity is considered depending on the frequency of the vibration. Regarding the boundary conditions of the velocity at the wall, we remark that there is a discontinuity of the velocity at the fluid-wall interface. The solutions for velocity and microrotation with the given conditions are obtained using the method of numerical inversion of Laplace transform. PMID- 26161778 TI - Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart. AB - Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p<0.05). Von Willebrand Factor, an endothelial differentiation marker, and MLC2v and Troponin T, markers for cardiomyogenic differentiation, were elevated in expression in adult progenitors after simulated microgravity. DNA repair genes and telomerase reverse transcriptase which are highly expressed in early stem cells were increased in expression in neonatal but not adult cardiac progenitors after growth under simulated microgravity conditions. Neonatal cardiac progenitors demonstrated higher levels of MESP1, OCT4, and brachyury, markers for early stem cells. MicroRNA profiling was used to further investigate the impact of simulated microgravity on cardiovascular progenitors. Fifteen microRNAs were significantly altered in expression, including microRNAs-99a and 100 (which play a critical role in cell dedifferentiation). These microRNAs were unchanged in adult cardiac progenitors. The effect of exposure to simulated microgravity in cardiovascular progenitors is age-dependent. Adult cardiac progenitors showed elevated expression of markers for endothelial and cardiomyogenic differentiation whereas neonatal progenitors acquired characteristics of dedifferentiating cells. PMID- 26161779 TI - Global Transcriptomic Profiling of Cardiac Hypertrophy and Fatty Heart Induced by Long-Term High-Energy Diet in Bama Miniature Pigs. AB - A long-term high-energy diet affects human health and leads to obesity and metabolic syndrome in addition to cardiac steatosis and hypertrophy. Ectopic fat accumulation in the heart has been demonstrated to be a risk factor for heart disorders, but the molecular mechanism of heart disease remains largely unknown. Bama miniature pigs were fed a high-fat, high-sucrose diet (HFHSD) for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased body weight (2.73-fold, P<0.01), insulin level (4.60-fold, P<0.01), heart weight (1.82-fold, P<0.05) and heart volume (1.60-fold, P<0.05) compared with the control pigs. To understand the molecular mechanisms of cardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips. Microarray analyses revealed that 1,022 genes were significantly differentially expressed (P<0.05, >=1.5-fold change), including 591 up-regulated and 431 down-regulated genes in the HFHSD group relative to the control group. KEGG analysis indicated that the observed heart disorder involved the signal transduction-related MAPK, cytokine, and PPAR signaling pathways, energy metabolism-related fatty acid and oxidative phosphorylation signaling pathways, heart function signaling-related focal adhesion, axon guidance, hypertrophic cardiomyopathy and actin cytoskeleton signaling pathways, inflammation and apoptosis pathways, and others. Quantitative RT-PCR assays identified several important differentially expressed heart-related genes, including STAT3, ACSL4, ATF4, FADD, PPP3CA, CD74, SLA-8, VCL, ACTN2 and FGFR1, which may be targets of further research. This study shows that a long term, high-energy diet induces obesity, cardiac steatosis, and hypertrophy and provides insights into the molecular mechanisms of hypertrophy and fatty heart to facilitate further research. PMID- 26161781 TI - The Polymerization of Aeromonas hydrophila AH-3 O-Antigen LPS: Concerted Action of WecP and Wzy. AB - The repeat units of heteropolymeric O antigen are synthesized at the cytosolic side of the inner bacterial membrane via the Wzx/Wzy-dependent assembly pathway. After being translocated across the membrane by Wzx, each repeat unit is polymerized by Wzy to form a glycan chain. In this study, we demonstrate the need of the corresponding enzyme transferring the initial HexNAc to undecaprenol phosphate (lipid carrier), together with the corresponding O-antigen polymerase (Wzy), to produce the Aeromonas hydrophila O:34-antigen. We suggest, the concerted action of WecA or P enzyme (UDP-HexNAc: polyprenol-P HexNAc-1-P transferase) and Wzy is involved in the mechanism responsible for the A. hydrophila O-antigen polymerization. PMID- 26161782 TI - CRISPR/Cas9n-Mediated Deletion of the Snail 1Gene (SNAI1) Reveals Its Role in Regulating Cell Morphology, Cell-Cell Interactions, and Gene Expression in Ovarian Cancer (RMG-1) Cells. AB - Snail1 is a transcription factor that induces the epithelial to mesenchymal transition (EMT). During EMT, epithelial cells lose their junctions, reorganize their cytoskeletons, and reprogram gene expression. Although Snail1 is a prominent repressor of E-cadherin transcription, its precise roles in each of the phenomena of EMT are not completely understood, particularly in cytoskeletal changes. Previous studies have employed gene knockdown systems to determine the functions of Snail1. However, incomplete protein knockdown is often associated with these systems, which may cause incorrect interpretation of the data. To more precisely evaluate the functions of Snail1, we generated a stable cell line with a targeted ablation of Snail1 (Snail1 KO) by using the CRISPR/Cas9n system. Snail1 KO cells show increased cell-cell adhesion, decreased cell-substrate adhesion and cell migration, changes to their cytoskeletal organization that include few stress fibers and abundant cortical actin, and upregulation of epithelial marker genes such as E-cadherin, occludin, and claudin-1. However, morphological changes were induced by treatment of Snail1 KO cells with TGF-beta. Other transcription factors that induce EMT were also induced by treatment with TGF-beta. The precise deletion of Snail1 by the CRISPR/Cas9n system provides clear evidence that loss of Snail1 causes changes in the actin cytoskeleton, decreases cell-substrate adhesion, and increases cell-cell adhesion. Treatment of RMG1 cells with TGF-beta suggests redundancy among the transcription factors that induce EMT. PMID- 26161783 TI - Increasing the Spatial Resolution of 3T Carotid MRI Has No Beneficial Effect for Plaque Component Measurement Reproducibility. AB - PURPOSE: Different in-plane resolutions have been used for carotid 3T MRI. We compared the reproducibility, as well as the within- and between reader variability of high and routinely used spatial resolution in scans of patients with atherosclerotic carotid artery disease. Since no consensus exists about the optimal segmentation method, we analysed all imaging data using two different segmentation methods. MATERIALS AND METHODS: In 31 patient with carotid atherosclerosis a high (0.25 * 0.25 mm2; HR) and routinely used (0.50 * 0.50 mm2; LR) spatial resolution carotid MRI scan were performed within one month. A fully blinded closed and a simultaneously open segmentation were used to quantify the lipid rich necrotic core (LRNC), calcified and loose matrix (LM) plaque area and the fibrous cap (FC) thickness. RESULTS: No significant differences were observed between scan-rescan reproducibility for HR versus LR measurements, nor did we find any significant difference between the within-reader and between-reader reproducibility. The same applies for differences between the open and closed reads. All intraclass correlation coefficients between scans and rescans for the LRNC, calcified and LM plaque area, as well as the FC thickness measurements with the open segmentation method were excellent (all above 0.75). CONCLUSIONS: Increasing the spatial resolution at the expense of the contrast-to-noise ratio does not improve carotid plaque component scan-rescan reproducibility in patients with atherosclerotic carotid disease, nor does using a different segmentation method. PMID- 26161784 TI - Duplex Real-Time RT-PCR Assays for the Detection and Typing of Epizootic Haemorrhagic Disease Virus. AB - Epizootic haemorrhagic disease virus (EHDV) may cause severe clinical episodes in some species of deer and sometimes in cattle. Laboratory diagnosis provides a basis for the design and timely implementation of disease control measures. There are seven distinct EHDV serotypes, VP2 coding segment 2 being the target for serotype specificity. This paper reports the development and validation of eight duplex real-time RT-PCR assays to simultaneously amplify the EHDV target (S9 for the pan-EHDV real-time RT-PCR assay and S2 for the serotyping assays) and endogenous control gene Beta-actin. Analytical and diagnostic sensitivity and specificity, inter- and intra-assay variation and efficiency were evaluated for each assay. All were shown to be highly specific and sensitive. PMID- 26161785 TI - Preparation of Cd/Pb Chalcogenide Heterostructured Janus Particles via Controllable Cation Exchange. AB - We developed a strategy for producing quasi-spherical nanocrystals of anisotropic heterostructures of Cd/Pb chalcogenides. The nanostructures are fabricated via a controlled cation exchange reaction where the Cd(2+) cation is exchanged for the Pb(2+) cation. The cation exchange reaction is thermally activated and can be controlled by adjusting the reaction temperature or time. We characterized the particles using TEM, XPS, PL, and absorption spectroscopy. With complete exchange, high quality Pb-chalcogenide quantum dots are produced. In addition to Cd(2+), we also find suitable conditions for the exchange of Zn(2+) cations for Pb(2+) cations. The cation exchange is anisotropic starting at one edge of the nanocrystals and proceeds along the ?111? direction producing a sharp interface at a (111) crystallographic plane. Instead of spherical core/shell structures, we produced and studied quasi-spherical CdS/PbS and CdSe/PbSe Janus-type heterostructures. Nontrivial PL behavior was observed from the CdS(e)/PbS(e) heterostructures as the Pb:Cd ratio is increased. PMID- 26161791 TI - Dimensionality of Rolled-up Nanomembranes Controls Neural Stem Cell Migration Mechanism. AB - We employ glass microtube structures fabricated by rolled-up nanotechnology to infer the influence of scaffold dimensionality and cell confinement on neural stem cell (NSC) migration. Thereby, we observe a pronounced morphology change that marks a reversible mesenchymal to amoeboid migration mode transition. Space restrictions preset by the diameter of nanomembrane topography modify the cell shape toward characteristics found in living tissue. We demonstrate the importance of substrate dimensionality for the migration mode of NSCs and thereby define rolled-up nanomembranes as the ultimate tool for single-cell migration studies. PMID- 26161792 TI - Evolving Concepts of Asthma. AB - Our understanding of asthma has evolved over time from a singular disease to a complex of various phenotypes, with varied natural histories, physiologies, and responses to treatment. Early therapies treated most patients with asthma similarly, with bronchodilators and corticosteroids, but these therapies had varying degrees of success. Similarly, despite initial studies that identified an underlying type 2 inflammation in the airways of patients with asthma, biologic therapies targeted toward these type 2 pathways were unsuccessful in all patients. These observations led to increased interest in phenotyping asthma. Clinical approaches, both biased and later unbiased/statistical approaches to large asthma patient cohorts, identified a variety of patient characteristics, but they also consistently identified the importance of age of onset of disease and the presence of eosinophils in determining clinically relevant phenotypes. These paralleled molecular approaches to phenotyping that developed an understanding that not all patients share a type 2 inflammatory pattern. Using biomarkers to select patients with type 2 inflammation, repeated trials of biologics directed toward type 2 cytokine pathways saw newfound success, confirming the importance of phenotyping in asthma. Further research is needed to clarify additional clinical and molecular phenotypes, validate predictive biomarkers, and identify new areas for possible interventions. PMID- 26161793 TI - Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi. AB - Sensitive, specific and rapid diagnostic tests for the detection of Orientia tsutsugamushi (O. tsutsugamushi) and Rickettsia typhi (R. typhi), the causative agents of scrub typhus and murine typhus, respectively, are necessary to accurately and promptly diagnose patients and ensure that they receive proper treatment. Recombinase polymerase amplification (RPA) assays using a lateral flow test (RPA-nfo) and real-time fluorescent detection (RPA-exo) were developed targeting the 47-kDa gene of O. tsutsugamushi or 17 kDa gene of R. typhi. The RPA assay was capable of detecting O. tsutsugamushi or R. typhi at levels comparable to that of the quantitative PCR method. Both the RPA-nfo and RPA-exo methods performed similarly with regards to sensitivity when detecting the 17 kDa gene of R. typhi. On the contrary, RPA-exo performed better than RPA-nfo in detecting the 47 kDa gene of O. tsutsugamushi. The clinical performance of the O. tsutsugamushi RPA assay was evaluated using either human patient samples or infected mouse samples. Eight out of ten PCR confirmed positives were determined positive by RPA, and all PCR confirmed negative samples were negative by RPA. Similar results were obtained for R. typhi spiked patient sera. The assays were able to differentiate O. tsutsugamushi and R. typhi from other phylogenetically related bacteria as well as mouse and human DNA. Furthermore, the RPA-nfo reaction was completed in 20 minutes at 37 degrees C followed by a 10 minute incubation at room temperature for development of an immunochromatographic strip. The RPA-exo reaction was completed in 20 minutes at 39 degrees C. The implementation of a cross contamination proof cassette to detect the RPA-nfo fluorescent amplicons provided an alternative to regular lateral flow detection strips, which are more prone to cross contamination. The RPA assays provide a highly time-efficient, sensitive and specific alternative to other methods for diagnosing scrub typhus or murine typhus. PMID- 26161794 TI - Human Leukocyte Antigens-B and -C Loci Associated with Posner-Schlossman Syndrome in a Southern Chinese Population. AB - The etiology of Posner-Schlossman syndrome (PSS) remains unknown. The association of human leukocyte antigens (HLA) allelic diversity with PSS has been poorly investigated. To evaluate the association of allelic polymorphisms of class I HLA A, -B and -C and class II HLA-DRB1 and -DQB1 with PSS, 100 unrelated patients with PSS and 128 age- and ethnically matched control subjects were recruited from a southern Chinese Han population. Polymorphisms in exons 2-4 for HLA-A, -B, -C loci, exon 2 for HLA-DRB1 and exons 2,3 for HLA-DQB1 were analyzed for association with PSS at allele and haplotype levels. The allele frequency of HLA C*1402 in PSS patients was significantly higher than that in controls (P = 0.002, OR = 4.12). This association survived the Bonferroni correction (Pc = 0.04). The allele frequency of HLA-B*1301 in PSS patients was lower than that in the control group (P = 0.003, OR = 0.21), although this association did not survive the Bonferroni correction (Pc = 0.16). In PSS patients, the haplotype frequencies of HLA-A*1101~C*1402 and B*5101~C*1402 were higher than that in controls (P = 0.03, OR = 4.44; P = 0.02, OR = 3.20; respectively), while the HLA-B*1301~C*0304 was lower than that in controls (P = 0.007, OR = 0.23), although these associations did not survive the Bonferroni correction (Pc > 0.16). This study for the first time demonstrated that polymorphisms at the HLA-B and HLA-C loci were nominally associated with PSS in the southern Chinese Han population. Our results suggest that HLA-C*1402, A*1101~C*1402 and B*5101~C*1402 might be risk factors for PSS, whereas HLA-B*1301 plus B*1301~C*0304 might be protective factors against PSS, but even larger datasets are required to confirm these findings. Findings from this study provide valuable new clues for investigating the mechanisms and development of new diagnosis and treatment for PSS. PMID- 26161795 TI - Twitter-Based Analysis of the Dynamics of Collective Attention to Political Parties. AB - Large-scale data from social media have a significant potential to describe complex phenomena in the real world and to anticipate collective behaviors such as information spreading and social trends. One specific case of study is represented by the collective attention to the action of political parties. Not surprisingly, researchers and stakeholders tried to correlate parties' presence on social media with their performances in elections. Despite the many efforts, results are still inconclusive since this kind of data is often very noisy and significant signals could be covered by (largely unknown) statistical fluctuations. In this paper we consider the number of tweets (tweet volume) of a party as a proxy of collective attention to the party, identify the dynamics of the volume, and show that this quantity has some information on the election outcome. We find that the distribution of the tweet volume for each party follows a log-normal distribution with a positive autocorrelation of the volume over short terms, which indicates the volume has large fluctuations of the log-normal distribution yet with a short-term tendency. Furthermore, by measuring the ratio of two consecutive daily tweet volumes, we find that the evolution of the daily volume of a party can be described by means of a geometric Brownian motion (i.e., the logarithm of the volume moves randomly with a trend). Finally, we determine the optimal period of averaging tweet volume for reducing fluctuations and extracting short-term tendencies. We conclude that the tweet volume is a good indicator of parties' success in the elections when considered over an optimal time window. Our study identifies the statistical nature of collective attention to political issues and sheds light on how to model the dynamics of collective attention in social media. PMID- 26161797 TI - Clinical Trial Adaptation by Matching Evidence in Complementary Patient Sub groups of Auxiliary Blinding Questionnaire Responses. AB - Clinical trial adaptation refers to any adjustment of the trial protocol after the onset of the trial. Such adjustment may take on various forms, including the change in the dose of administered medicines, the frequency of administering an intervention, the number of trial participants, or the duration of the trial, to name just some possibilities. The main goal is to make the process of introducing new medical interventions to patients more efficient, either by reducing the cost or the time associated with evaluating their safety and efficacy. The principal challenge, which is an outstanding research problem, is to be found in the question of how adaptation should be performed so as to minimize the chance of distorting the outcome of the trial. In this paper we propose a novel method for achieving this. Unlike most of the previously published work, our approach focuses on trial adaptation by sample size adjustment i.e. by reducing the number of trial participants in a statistically informed manner. We adopt a stratification framework recently proposed for the analysis of trial outcomes in the presence of imperfect blinding and based on the administration of a generic auxiliary questionnaire that allows the participants to express their belief concerning the assigned intervention (treatment or control). We show that this data, together with the primary measured variables, can be used to make the probabilistically optimal choice of the particular sub-group a participant should be removed from if trial size reduction is desired. Extensive experiments on a series of simulated trials are used to illustrate the effectiveness of our method. PMID- 26161799 TI - Novel Mixed Cobalt/Chromium Phosphate NaCoCr2(PO4)3 Showing Spin-Flop Transition. AB - We describe the synthesis and the crystallographic and magnetic properties of a novel NaCoCr2(PO4)3 phosphate. A conventional solid-state reaction was used to obtain single-phase powders. A Rietveld analysis of powder X-ray diffraction data proposes an orthorhombic symmetry similar to alpha-CrPO4-type structure in space group Imma with the following unit cell parameters: a = 10.413(1) A; b = 13.027(1) A; c = 6.372(1) A. The framework consists of PO4 tetrahedra, M(1)O6 (M(1) = Cr) octahedra, and M(2)2O10 (M(2) = 0.5Cr+0.5Co) binuclear unit of edge sharing MO6 octahedra. It can be described in terms of two building blocks: sheets consisting of corner-sharing M(2)2O10 units with PO4 tetrahedra found parallel to the (b,c) plane, and chains made by corner-sharing CrO6 octahedra and PO4 tetrahedra running along the b axis. From the interconnection of the sheets and chains, a 3D rigid skeleton is formed, exhibiting two kinds of intersecting tunnel channels containing the Na(+) ions. The proposed structure derives from the alpha-CrPO4-type structure considering a positive charge balance according to the equation Cr(3+) -> Co(2+) + Na(+), resulting in sodium countercation introduction within the unoccupied channels shown in the alpha-CrPO4 framework. Temperature-dependent DC and AC magnetic susceptibility is indicative of a long range magnetic ordering occurring at 32 K. Further, spin-flop transition sheds light on a chromium-based phosphate for the first time. PMID- 26161798 TI - Regulatory Action of Calcium Ion on Cyclic AMP-Enhanced Expression of Implantation-Related Factors in Human Endometrial Cells. AB - Decidualization of human endometrial stroma and gland development is mediated through cyclic AMP (cAMP), but the role of intracellular calcium ion (Ca2+) on cAMP mediated-signaling in human endometrial stroma and glandular epithelia has not been well-characterized. The present study was designed to investigate the role of intracellular Ca2+ on cAMP mediated-decidualization and gland maturation events, which can be identified by the up-regulation of prolactin and IGF-binding protein (IGFBP)1 in human endometrial stromal cells (ESCs), and cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) and glandular epithelial EM-1 cells. Increases in decidual prolactin and IGFBP-1 transcript levels, induced by cAMP-elevating agents forskolin or dibutyryl cyclic AMP, were inhibited by Ca2+ influx into ESCs with Ca2+ ionophores (alamethicin, ionomycin) in a dose-dependent manner. Conversely, inhibitors of Ca2+ influx through L-type voltage-dependent Ca2+ channel (VDCC), nifedipine and verapamil, enhanced the decidual gene expression. Furthermore, dantrolene, an inhibitor of Ca2+ release from the intracellular Ca2+ store, up-regulated prolactin and IGFBP-1 expression. Ca2+ ionophores decreased intracellular cAMP concentrations, whereas nifedipine, verapamil or dantrolene increased cAMP concentrations in ESCs. In glandular epithelial cells, similar responses in COX2 expression and PGE2 production were found when intracellular cAMP levels were up-regulated by decreases in Ca2+ concentrations. Thus, a marked decrease in cytosolic Ca2+ levels caused the elevation of cAMP concentrations, resulting in enhanced expression of implantation-related factors including decidual markers. These findings suggest that fluctuation in cytosolic Ca2+ concentrations alters intracellular cAMP levels, which then regulate differentiation of endometrial stromal and glandular epithelial cells. PMID- 26161796 TI - Fish Oil Accelerates Diet-Induced Entrainment of the Mouse Peripheral Clock via GPR120. AB - The circadian peripheral clock is entrained by restricted feeding (RF) at a fixed time of day, and insulin secretion regulates RF-induced entrainment of the peripheral clock in mice. Thus, carbohydrate-rich food may be ideal for facilitating RF-induced entrainment, although the role of dietary oils in insulin secretion and RF-induced entrainment has not been described. The soybean oil component of standard mouse chow was substituted with fish or soybean oil containing docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). Tuna oil (high DHA/EPA), menhaden oil (standard), and DHA/EPA dissolved in soybean oil increased insulin secretion and facilitated RF-induced phase shifts of the liver clock as represented by the bioluminescence rhythms of PER2::LUCIFERASE knock-in mice. In this model, insulin depletion blocked the effect of tuna oil and fish oil had no effect on mice deficient for GPR120, a polyunsaturated fatty acid receptor. These results suggest food containing fish oil or DHA/EPA is ideal for adjusting the peripheral clock. PMID- 26161800 TI - Sentinel Node Biopsy for the Head and Neck Using Contrast-Enhanced Ultrasonography Combined with Indocyanine Green Fluorescence in Animal Models: A Feasibility Study. AB - BACKGROUND: Sentinel node navigation surgery is gaining popularity in oral cancer. We assessed application of sentinel lymph node navigation surgery to pharyngeal and laryngeal cancers by evaluating the combination of contrast enhanced ultrasonography and indocyanine green fluorescence in animal models. METHODS: This was a prospective, nonrandomized, experimental study in rabbit and swine animal models. A mixture of indocyanine green and Sonazoid was used as the tracer. The tracer mixture was injected into the tongue, larynx, or pharynx. The sentinel lymph nodes were identified transcutaneously by infra-red camera and contrast-enhanced ultrasonography. Detection time and extraction time of the sentinel lymph nodes were measured. The safety of the tracer mixture in terms of mucosal reaction was evaluated macroscopically and microscopically. RESULTS: Sentinel lymph nodes were detected transcutaneously by contrast-enhanced ultrasonography alone. The number of sentinel lymph nodes detected was one or two. Despite observation of contrast enhancement of Sonazoid for at least 90 minutes, the number of sentinel lymph nodes detected did not change. The average extraction time of sentinel lymph nodes was 4.8 minutes. Indocyanine green fluorescence offered visual information during lymph node biopsy. The safety of the tracer was confirmed by absence of laryngeal edema both macro and microscopically. CONCLUSIONS: The combination method of indocyanine green fluorescence and contrast-enhanced ultrasonography for detecting sentinel lymph nodes during surgery for head and neck cancer seems promising, especially for pharyngeal and laryngeal cancer. Further clinical studies to confirm this are warranted. PMID- 26161802 TI - Proposed Ligand-Centered Electrocatalytic Hydrogen Evolution and Hydrogen Oxidation at a Noninnocent Mononuclear Metal-Thiolate. AB - The noninnocent coordinatively saturated mononuclear metal-thiolate complex ReL3 (L = diphenylphosphinobenzenethiolate) serves as an electrocatalyst for hydrogen evolution or hydrogen oxidation dependent on the presence of acid or base and the applied potential. ReL3 reduces acids to H2 in dichloromethane with an overpotential of 380 mV and a turnover frequency of 32 +/- 3 s(-1). The rate law displays a second-order dependence on acid concentration and a first-order dependence on catalyst concentration with an overall third-order rate constant (k) of 184 +/- 2 M(-2) s(-1). Reactions with deuterated acid display a kinetic isotope effect of 9 +/- 1. In the presence of base, ReL3 oxidizes H2 with a turnover frequency of 4 +/- 1 s(-1). The X-ray crystal structure of the monoprotonated species [Re(LH)L2](+), an intermediate in both catalytic H2 evolution and oxidation, has been determined. A ligand-centered mechanism, which does not require metal hydride intermediates, is suggested based on similarities to the redox-regulated, ligand-centered binding of ethylene to ReL3. PMID- 26161801 TI - 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice. AB - OBJECTIVE: Sonodynamic therapy (SDT) is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5 Aminolevulinic Acid (5-ALA)-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro. METHODS: The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (DeltapsiM), ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined. RESULTS: Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2) for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (P<0.01) and reduced the viability of UMR-106 cells (p<0.05). ALA-SDT further reduced the tumor volumes and viability of UMR-106 cells (p<0.01 for both). Pre-treatment with 5 ALA significantly enhanced the SDT-mediated apoptosis (p<0.01) and morphological changes. Furthermore, ALA-SDT significantly reduced the levels of DeltapsiM, but increased levels of ROS in UMR-106 cells (p<0.05 or p<0.01 vs. the Control or the Ultrasound). Moreover, ALA-SDT inhibited the proliferation of osteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (p<0.05 or p<0.01 vs. the Control or the Ultrasound). CONCLUSIONS: The ALA-SDT significantly inhibited osteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway. PMID- 26161803 TI - What's in a Surname? Physique, Aptitude, and Sports Type Comparisons between Tailors and Smiths. AB - Combined heredity of surnames and physique, coupled with past marriage patterns and trade-specific physical aptitude and selection factors, may have led to differential assortment of bodily characteristics among present-day men with specific trade-reflecting surnames (Tailor vs. Smith). Two studies reported here were partially consistent with this genetic-social hypothesis, first proposed by Baumler (1980). Study 1 (N = 224) indicated significantly higher self-rated physical aptitude for prototypically strength-related activities (professions, sports, hobbies) in a random sample of Smiths. The counterpart effect (higher aptitude for dexterity-related activities among Tailors) was directionally correct, but not significant, and Tailor-Smith differences in basic physique variables were nil. Study 2 examined two large total-population-of-interest datasets (Austria/Germany combined, and UK: N = 7001 and 20,532) of men's national high-score lists for track-and-field events requiring different physiques. In both datasets, proportions of Smiths significantly increased from light-stature over medium-stature to heavy-stature sports categories. The predicted counterpart effect (decreasing prevalences of Tailors along these categories) was not supported. Related prior findings, the viability of possible alternative interpretations of the evidence (differential positive selection for trades and occupations, differential endogamy and assortative mating patterns, implicit egotism effects), and directions for further inquiry are discussed in conclusion. PMID- 26161804 TI - Examining the Echolalia Literature: Where Do Speech-Language Pathologists Stand? AB - PURPOSE: Echolalia is a common element in the communication of individuals with autism spectrum disorders. Recent contributions to the literature reflect significant disagreement regarding how echolalia should be defined, understood, and managed. The purpose of this review article is to give speech-language pathologists and others a comprehensive view of the available perspectives on echolalia. METHOD: Published literature from the disciplines of behavioral intervention, linguistics, and speech-language intervention is discussed. Special areas of focus include operational definitions, rationales associated with various approaches, specific procedures used to treat or study echolalic behavior, and reported conclusions. CONCLUSIONS: Dissimilarities in the definition and understanding of echolalia have led to vastly different approaches to management. Evidence-based practice protocols are available to guide speech language interventionists in their work with individuals with autism spectrum disorders. PMID- 26161806 TI - Assessment of hormone-like activities in Ginkgo biloba, Elettaria cardamomum and Plantago ovata extracts using in vitro receptor-specific bioassays. AB - Medicinal plants are widely used for the treatment of diseases and for the development of new drugs. This study was designed to determine the presence of hormone-like activities dependent on the activation of human estrogen receptor alpha (hERa) and/or androgen receptor (hAR) in methanol extracts prepared from three medicinal plants historically and currently used for therapeutic purposes: Ginkgo biloba leaves (GBL), Elettaria cardamomum seeds (ECS) and Plantago ovata seeds (POS). After a solid-liquid extraction (SLE) step, their effects on hERa function were assessed in MCF-7 breast cancer cells using the E-Screen bioassay, and their ability to induce hAR-mediated reporter gene expression was evaluated using the androgen-sensitive stable prostatic PALM cell line. Unlike POS extracts, GBL and ECS extracts showed estrogenic (0.07 and 0.20 nM E2Eq mg(-1), respectively) and anti-estrogenic (0.01 and 0.02 MUM ICI182780Eq mg(-1), respectively) activities. ECS extracts evidenced androgenic activity (0.30 nM R1881Eq mg(-1)) and POS extracts anti-androgenic activity (22.30 MUM ProcEq mg( 1)). According to these findings, these plant extracts may interfere with the endocrine system via one or more hormonal receptors, and further investigation is warranted into their role as endocrine disrupters in humans. PMID- 26161808 TI - Calcium Carbonate Nanoplate Assemblies with Directed High-Energy Facets: Additive Free Synthesis, High Drug Loading, and Sustainable Releasing. AB - Developing drug delivery systems (DDSs) with high drug-loading capacity and sustainable releasing is critical for long-term chemotherapeutic efficacy, and it still remains challenging. Herein, vaterite CaCO3 nanoplate assemblies with exposed high-energy {001} facets have been synthesized via a novel, additive-free strategy. The product shows a high doxorubicin-loading capacity (65%); the best of all the CaCO3-based DDSs so far. Also, the product's sustainable releasing performance and its inhibition of the initial burst release, together, endow it with long-term drug efficacy. The work may shed light on exposing directed high energy facets for rationally designing of a drug delivery system with long-term efficacy. PMID- 26161807 TI - Integrative proteomics to understand the transmission mechanism of Barley yellow dwarf virus-GPV by its insect vector Rhopalosiphum padi. AB - Barley yellow dwarf virus-GPV (BYDV-GPV) is transmitted by Rhopalosiphum padi and Schizaphis graminum in a persistent nonpropagative manner. To improve our understanding of its transmission mechanism by aphid vectors, we used two approaches, isobaric tags for relative and absolute quantitation (iTRAQ) and yeast two-hybrid (YTH) system, to identify proteins in R. padi that may interact with or direct the spread of BYDV-GPV along the circulative transmission pathway. Thirty-three differential aphid proteins in viruliferous and nonviruliferous insects were identified using iTRAQ coupled to 2DLC-MS/MS. With the yeast two hybrid system, 25 prey proteins were identified as interacting with the readthrough protein (RTP) and eight with the coat protein (CP), which are encoded by BYDV-GPV. Among the aphid proteins identified, most were involved in primary energy metabolism, synaptic vesicle cycle, the proteasome pathway and the cell cytoskeleton organization pathway. In a systematic comparison of the two methods, we found that the information generated by the two methods was complementary. Taken together, our findings provide useful information on the interactions between BYDV-GPV and its vector R. padi to further our understanding of the mechanisms regulating circulative transmission in aphid vectors. PMID- 26161809 TI - Predicting Alcohol Misuse Among College Students in the US and South Korea. AB - This study examines contributing factors of alcohol misuse among college students in South Korea and the U.S. Exploratory factor analyses (EFA) on measurements of alcohol expectancy, alcohol efficacy, and accommodation resulted in social and personal causes for alcohol misuse. Social causes alone predicted alcohol misuse for both countries. Social factors constituted a much stronger predictor of alcohol misuse among South Korean students than among American students. Practical implications for effective deterrence of student binge drinking are discussed. PMID- 26161810 TI - The Molecular Basis of alpha-Thalassemia in the Qatari Pediatric Population. AB - alpha-Thalassemia (alpha-thal) is widely reported in the Arabian Peninsula as one of the main causes of asymptomatic microcytic hypochromic red blood cells with or without anemia in the pediatric population. This is the first study that provides information about the molecular basis of alpha-thal in the Qatari population. Qatari school children between the ages of 5 and 15, exhibiting laboratory findings suggestive of microcytic anemia were pooled, and those with a mean corpuscular volume (MCV) of <80.0 fL and a hemoglobin (Hb) electropherogram that ruled out beta-thalassemia (beta-thal), were narrowed down to a group of 127. This group was screened for the -alpha(3.7) (rightward) deletion, and the alpha( 5 nt), alpha(polyA1) (alpha(T-Saudi)), alpha(polyA2) mutations. A second group of randomly selected Qatari individuals was also screened in order to determine the population's allele frequency for the -alpha(3.7) deletion. Thirty-nine point four percent of the individuals with microcytic hypochromic anemia were positive for the -alpha(3.7) deletion (heterozygotes 30.0%, homozygotes 9.4%), 2.6% were positive for the alpha(polyA1) deletion and 0.8% positive for the alpha(-5 nt) mutation. None of the children exhibited changes in alpha(polyA2). Analysis of the random samples determined that 26.4% were heterozygous and 4.5% homozygous for the -alpha(3.7) deletion with a 17.7% allele frequency. Our results suggest that a significant number of the Qatari pediatric population with microcytic hypochromic anemia are carriers of alpha-thal mutations. However, 45.6% of the children failed to exhibit any of the above four mutations tested. This suggests the possibility of other mutations in the Qatari pediatric population that are yet to be elicited. PMID- 26161811 TI - Elucidating time-dependent changes in the urinary metabolome of renal transplant patients by a combined (1)H NMR and GC-MS approach. AB - Urine metabolomic profiling can identify biochemical alterations resulting from various injuries affecting the graft outcome after renal transplantation. Here, we aimed to describe in depth the metabolite content of urines of renal transplant patients and to link it with the major injury factors acting at critical stages following transplantation. Morning urine samples were prospectively collected from 38 kidney transplant patients at 7 days (D7), 3 months (M3) and 12 months (M12) after transplantation. Twenty-five patients were treated with tacrolimus (Tac) and thirteen patients with cyclosporine (CsA). (1)H NMR (proton nuclear magnetic resonance) and gas chromatography-mass spectrometry (GC-MS) were used to examine the overall metabolomic signature of each sample. Multivariate analysis was performed to study the changes in the metabolic profile over time and their dependency on the type of calcineurin inhibitor (CNI) administered to patients. Biological pathways affected by transplantation were identified using a metabolomics pathway analysis (MetPA) web-tool. The metabolic profile of urine samples clearly varied with time. Markers of medullary injury, tubule cell oxidative metabolism and impaired tubular reabsorption or secretion were present at D7. Differences in metabolic profiles became less marked as time passed on, urine content being quite similar at M3 and M12. The metabolite profile tended to differ between patients receiving Tac and those receiving CsA but no clear discriminating profiles can be found. The combination of (1)H-NMR and GC-MS for the analysis of urine metabolomic profiles is a very useful method to study patho-physiological alterations in kidney transplant patients over time. PMID- 26161812 TI - Environmental Progestins Progesterone and Drospirenone Alter the Circadian Rhythm Network in Zebrafish (Danio rerio). AB - Progestins alter hormone homeostasis and may result in reproductive effects in humans and animals. Thus far, studies in fish have focused on the hypothalamic pituitary-gonadal (HPG)-axis and reproduction, but other effects have little been investigated. Here we report that progesterone (P4) and drospirenone (DRS) interfere with regulation of the circadian rhythm in fish. Breeding pairs of adult zebrafish were exposed to P4 and DRS at concentrations between 7 and 13 650 ng/L for 21 days. Transcriptional analysis revealed significant and dose dependent alterations of the circadian rhythm network in the brain with little effects in the gonads. Significant alterations of many target transcripts occurred even at environmental relevant concentrations of 7 ng/L P4 and at 99 ng/L DRS. They were fully consistent with the well-described circadian rhythm negative/positive feedback loops. Transcriptional alterations of the circadian rhythm network were correlated with those in the HPG-Liver-axis. Fecundity was decreased at 742 (P4) and 2763 (DRS) ng/L. Dose-dependent alterations in the circadian rhythm network were also observed in F1 eleuthero-embryos. Our results suggest a potential target of environmental progestins, the circadian rhythm network, in addition to the adverse reproductive effects. Forthcoming studies should show whether the transcriptional alterations in circadian rhythm translate into physiological effects. PMID- 26161814 TI - Template-Free Synthesis of Ruthenium Oxide Nanotubes for High-Performance Electrochemical Capacitors. AB - One-dimensional, hydrous ruthenium oxide nanotubes (RuO2.1.84H2O) have been successfully achieved using a template-free, microwave-hydrothermal process. These were found to be amorphous in nature and have a large specific surface area of 250 m(2).g(-1), producing a specific and volumetric capacitance of 511 F.g(-1) and 531 F.cm(-3), respectively, at a discharging current density of 0.5 A.g(-1). When used as an electrode material in an electrochemical capacitor or ultracapacitor, they produced a significant improvement in capacitance, rate capability, and cyclability that can be attributed to the hollow nature of tubes allowing greater contact between the active surface of the electrode and the electrolyte. PMID- 26161813 TI - Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer. AB - Biliary cancers (BC) are rare, chemoresistant and are associated with a poor prognosis. Targeting the Akt pathway is of significance in BC. We hypothesized that the allosteric inhibitor MK-2206 will be active in BC. This was a multi institutional phase II study of MK-2206 given to patients with advanced, refractory BC. The primary end point was overall response rate. We also characterized pharmacokinetic profiles of MK-2206 in these patients and explored its potential correlation with clinical outcomes. Eight patients were enrolled prior to early termination of the trial. All patients had received prior systemic therapy. The best response observed was stable disease, exceeding 12 weeks in two patients. Toxicities were mild and tolerable. MK-2206 exhibited a pharmacokinetic profile with an apparent slow absorption followed by biphasic elimination in these patients with BC. No significant association was observed between the pharmacokinetic properties of MK-2206 and clinical outcomes. MK-2206 as a single agent in BC is tolerable with pharmacokinetic properties similar to patients with other solid tumors. No clinical activity was observed in this limited population. Further development of Akt inhibitors may need to focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy and prospective patient selection. PMID- 26161815 TI - Fusion of Scores in a Detection Context Based on Alpha Integration. AB - We present a new method for fusing scores corresponding to different detectors (two-hypotheses case). It is based on alpha integration, which we have adapted to the detection context. Three optimization methods are presented: least mean square error, maximization of the area under the ROC curve, and minimization of the probability of error. Gradient algorithms are proposed for the three methods. Different experiments with simulated and real data are included. Simulated data consider the two-detector case to illustrate the factors influencing alpha integration and demonstrate the improvements obtained by score fusion with respect to individual detector performance. Two real data cases have been considered. In the first, multimodal biometric data have been processed. This case is representative of scenarios in which the probability of detection is to be maximized for a given probability of false alarm. The second case is the automatic analysis of electroencephalogram and electrocardiogram records with the aim of reproducing the medical expert detections of arousal during sleeping. This case is representative of scenarios in which probability of error is to be minimized. The general superior performance of alpha integration verifies the interest of optimizing the fusing parameters. PMID- 26161816 TI - Is First-Order Vector Autoregressive Model Optimal for fMRI Data? AB - We consider the problem of selecting the optimal orders of vector autoregressive (VAR) models for fMRI data. Many previous studies used model order of one and ignored that it may vary considerably across data sets depending on different data dimensions, subjects, tasks, and experimental designs. In addition, the classical information criteria (IC) used (e.g., the Akaike IC (AIC)) are biased and inappropriate for the high-dimensional fMRI data typically with a small sample size. We examine the mixed results on the optimal VAR orders for fMRI, especially the validity of the order-one hypothesis, by a comprehensive evaluation using different model selection criteria over three typical data types -a resting state, an event-related design, and a block design data set--with varying time series dimensions obtained from distinct functional brain networks. We use a more balanced criterion, Kullback's IC (KIC) based on Kullback's symmetric divergence combining two directed divergences. We also consider the bias-corrected versions (AICc and KICc) to improve VAR model selection in small samples. Simulation results show better small-sample selection performance of the proposed criteria over the classical ones. Both bias-corrected ICs provide more accurate and consistent model order choices than their biased counterparts, which suffer from overfitting, with KICc performing the best. Results on real data show that orders greater than one were selected by all criteria across all data sets for the small to moderate dimensions, particularly from small, specific networks such as the resting-state default mode network and the task-related motor networks, whereas low orders close to one but not necessarily one were chosen for the large dimensions of full-brain networks. PMID- 26161817 TI - Online Direct Density-Ratio Estimation Applied to Inlier-Based Outlier Detection. AB - Many machine learning problems, such as nonstationarity adaptation, outlier detection, dimensionality reduction, and conditional density estimation, can be effectively solved by using the ratio of probability densities. Since the naive two-step procedure of first estimating the probability densities and then taking their ratio performs poorly, methods to directly estimate the density ratio from two sets of samples without density estimation have been extensively studied recently. However, these methods are batch algorithms that use the whole data set to estimate the density ratio, and they are inefficient in the online setup, where training samples are provided sequentially and solutions are updated incrementally without storing previous samples. In this letter, we propose two online density-ratio estimators based on the adaptive regularization of weight vectors. Through experiments on inlier-based outlier detection, we demonstrate the usefulness of the proposed methods. PMID- 26161818 TI - Relations Among Some Low-Rank Subspace Recovery Models. AB - Recovering intrinsic low-dimensional subspaces from data distributed on them is a key preprocessing step to many applications. In recent years, a lot of work has modeled subspace recovery as low-rank minimization problems. We find that some representative models, such as robust principal component analysis (R-PCA), robust low-rank representation (R-LRR), and robust latent low-rank representation (R-LatLRR), are actually deeply connected. More specifically, we discover that once a solution to one of the models is obtained, we can obtain the solutions to other models in closed-form formulations. Since R-PCA is the simplest, our discovery makes it the center of low-rank subspace recovery models. Our work has two important implications. First, R-PCA has a solid theoretical foundation. Under certain conditions, we could find globally optimal solutions to these low rank models at an overwhelming probability, although these models are nonconvex. Second, we can obtain significantly faster algorithms for these models by solving R-PCA first. The computation cost can be further cut by applying low-complexity randomized algorithms, for example, our novel l2,1 filtering algorithm, to R-PCA. Although for the moment the formal proof of our l2,1 filtering algorithm is not yet available, experiments verify the advantages of our algorithm over other state-of-the-art methods based on the alternating direction method. PMID- 26161819 TI - A Fast Algorithm for Learning Overcomplete Dictionary for Sparse Representation Based on Proximal Operators. AB - We present a fast, efficient algorithm for learning an overcomplete dictionary for sparse representation of signals. The whole problem is considered as a minimization of the approximation error function with a coherence penalty for the dictionary atoms and with the sparsity regularization of the coefficient matrix. Because the problem is nonconvex and nonsmooth, this minimization problem cannot be solved efficiently by an ordinary optimization method. We propose a decomposition scheme and an alternating optimization that can turn the problem into a set of minimizations of piecewise quadratic and univariate subproblems, each of which is a single variable vector problem, of either one dictionary atom or one coefficient vector. Although the subproblems are still nonsmooth, remarkably they become much simpler so that we can find a closed-form solution by introducing a proximal operator. This leads to an efficient algorithm for sparse representation. To our knowledge, applying the proximal operator to the problem with an incoherence term and obtaining the optimal dictionary atoms in closed form with a proximal operator technique have not previously been studied. The main advantages of the proposed algorithm are that, as suggested by our analysis and simulation study, it has lower computational complexity and a higher convergence rate than state-of-the-art algorithms. In addition, for real applications, it shows good performance and significant reductions in computational time. PMID- 26161820 TI - A Novel Reconstruction Framework for Time-Encoded Signals with Integrate-and-Fire Neurons. AB - Integrate-and-fire neurons are time encoding machines that convert the amplitude of an analog signal into a nonuniform, strictly increasing sequence of spike times. Under certain conditions, the encoded signals can be reconstructed from the nonuniform spike time sequences using a time decoding machine. Time encoding and time decoding methods have been studied using the nonuniform sampling theory for band-limited spaces, as well as for generic shift-invariant spaces. This letter proposes a new framework for studying IF time encoding and decoding by reformulating the IF time encoding problem as a uniform sampling problem. This framework forms the basis for two new algorithms for reconstructing signals from spike time sequences. We demonstrate that the proposed reconstruction algorithms are faster, and thus better suited for real-time processing, while providing a similar level of accuracy, compared to the standard reconstruction algorithm. PMID- 26161821 TI - Periarterial Plaques (Kyrieleis' Arteriolitis) in a Case of Bilateral Acute Retinal Necrosis. AB - PURPOSE: To describe unilateral periarterial plaque in a case of bilateral acute retinal necrosis (BARN) due to varicella zoster virus (VZV). METHODS: Case report. RESULTS: A 43-year-old diabetic male presented to us with dimness of vision in the left eye for three months. He was already on oral steroids and anti viral therapy. Best-corrected visual acuity was 6/6 OD and hand movements close to face OS. The right eye showed inferior and temporal retinal thinning and pigmentation and periarterial whitish focal Kyrieleis' plaques, specifically along arterioles. Left eye had mild vitritis, optic disc pallor, arteriolar attenuation, with retinal whitening and areas of pigmentation involving 360 degrees of peripheral retina along with some involvement of the posterior pole. Serology for human immunodeficiency virus (HIV), herpes simplex virus (HSV), and cytomegalo virus (CMV) was negative. IgM for VZV was positive. Oral Valacyclovir 1 g thrice daily was continued and a slow taper of oral steroids was instituted. CONCLUSIONS: ARN should be considered as a differential diagnosis in cases with Kyrieleis' plaques and a peripheral retinal examination must be done to rule out patches of healed retinitis and vasculitis. PMID- 26161824 TI - A comprehensive patents review on cannabinoid 1 receptor antagonists as antiobesity agents. AB - INTRODUCTION: Obesity is a rapidly expanding worldwide health problem. Various targets are investigated presently for the treatment of obesity, but there remains an unmet need for an effective drug therapy with acceptable efficacy levels and reduced side effects. Targeting peripherally located cannabinoid 1 (CB1) receptors is an attractive strategy as these receptors play a vital role in energy homeostasis. AREAS COVERED: CB1 receptor antagonists constitute one of the most important categories of compounds of interest for the control of obesity. In this review, the authors focus on recent advances (since 2007) in diverse chemical classes of patented compounds belonging to the category of CB1 receptor antagonists. EXPERT OPINION: Safer CB1 receptor antagonists for the treatment of obesity can be discovered by developing such compounds that act peripherally. Increasing the polar service area, decreasing the lipophilicity and designing of neutral antagonists and allosteric inhibitors are some interesting strategies that could offer promising results. PMID- 26161825 TI - Suicidal ideation in family carers of people with dementia. AB - OBJECTIVE: Two small studies have suggested that family carers of people with dementia may be a high-risk group for suicide. The objective of this study was to further explore the rate of suicidal ideation in a large sample of carers and identify psychosocial risk and protective factors. METHOD: A cross-sectional survey was conducted with 566 family carers. The survey included measures of suicidality, self-efficacy, physical health, depression, anxiety, hopelessness, optimism, burden, coping strategies, and social support. RESULTS: Sixteen percent of carers had contemplated suicide more than once in the previous year. There were univariate differences between suicidal and non-suicidal carers on self efficacy, social support, coping, burden, depression, anxiety, hopelessness, optimism, reasons for living, and symptoms of dementia, as well as age and income management. In a multivariate model, age, depression, and reasons for living predicted suicidal ideation. In tests for mediation, satisfaction with social support and dysfunctional coping had indirect effects on suicidal ideation via depression. CONCLUSION: Family carers of people with dementia have high rates of suicidal ideation, with depression a risk factor and increasing age and reasons for living as protective factors. Depression and reasons for living should be targeted in interventions to reduce suicide risk in dementia carers. PMID- 26161830 TI - Multifunctional metal-organic frameworks: from academia to industrial applications. AB - After three decades of intense and fundamental research on metal-organic frameworks (MOFs), is there anything left to say or to explain? The synthesis and properties of MOFs have already been comprehensively described elsewhere. It is time, however, to prove the nature of their true usability: technological applications based on these extended materials require development and implementation as a natural consequence of the up-to-known intensive research focused on their design and preparation. The current large number of reviews on MOFs emphasizes practical strategies to develop novel networks with varied crystal size, shape and topology, being mainly devoted to academic concerns. The present survey intends to push the boundaries and summarise the state-of-the-art on the preparation of promising (multi)functional MOFs in worldwide laboratories and their use as materials for industrial implementation. This review starts, on the one hand, to describe several tools and striking examples of remarkable and recent (multi)functional MOFs exhibiting outstanding properties (e.g., in gas adsorption and separation, selective sorption of harmful compounds, heterogeneous catalysis, luminescent and corrosion protectants). On the other hand, and in a second part, it intends to use these examples of MOFs to incite scientists to move towards the transference of knowledge from the laboratories to the industry. Within this context, we exhaustively review the many efforts of several worldwide commercial companies to bring functional MOFs towards the daily use, analysing the various patents and applications reported to date. Overall, this review goes from the very basic concepts of functional MOF engineering and preparation ending up in their industrial production on a large scale and direct applications in society. PMID- 26161831 TI - Our favorite cases. PMID- 26161832 TI - The "surgery first" approach with passive self-ligating brackets for expedited treatment of skeletal Class III malocclusion. PMID- 26161833 TI - Compunded topical anesthetics in orthodontics. PMID- 26161834 TI - Effective mechanics for vertical control with the Forsus Fatigue Resistant Device. PMID- 26161835 TI - A comprehensive orthodontic model analysis app. PMID- 26161836 TI - Compensatory retreatment of an adult Class II deep-bite patient. PMID- 26161837 TI - Open-bite treatment using maxillary and mandibular miniplates. PMID- 26161838 TI - Introducing the fast track surgery principles can reduce length of stay after autologous breast reconstruction using free flaps: A case control study. AB - INTRODUCTION: The concept of fast-track surgery (FTS) is a peri- and postoperative care concept developed to reduce length of hospital stay (LOS) and morbidity after surgery. FTS programmes have been reported from other surgical specialities, but there are few reports of FTS in plastic surgery. MATERIALS AND METHODS: Autologous breast reconstructions have been performed with abdominal free flaps since 1994. In 2006, an FTS program was introduced. Important changes in procedure were: early mobilisation, fewer/faster removal of drains and urinary catheter, discontinuation of epidural analgesia, planned early discharge, and multimodal opioid-sparing analgesia. The results from all unilateral, breast reconstructions in the first 5 years after the implementation of the FTS (n = 177) were compared to results prior to the FTS (n = 292). Flap type, operating time, blood loss and ischaemic time, LOS, early flap related and systemic complications (< 30 days) were analysed. RESULTS: FTS significantly reduced mean LOS from 7.4 days to 6.2 days (p = 0.0002). When compared to pre-FTS results, similar flap types, operating time, blood loss and ischaemic time were found. LOS > 7 days were due to complications, the most common being haematoma. Prevalence of complications (6.5 vs 7.9%) and flap loss (2 vs 2%) did not increase. Haematomas seemed more frequent with the use of NSAID than with COX-2 inhibitors (9 vs 4%); however, the difference was not statistically significant. CONCLUSION: By introducing a simple, peri- and postoperative care concept it is possible to reduce LOS after microsurgery by at least 1 day without an increase in complications or flap loss. PMID- 26161839 TI - Neurotoxicity associated with exposure to 1-bromopropane in golf-club cleansing workers. AB - BACKGROUND: 1-Bromopropane (1-BP) is an alternative to ozone-depleting solvent that is used in degreasing, dry cleaning, spray adhesives, and aerosol solvents. Occupational exposure to 1-BP is associated with adverse peripheral sensory, motor, and central nervous system (CNS) effects. We report our Health Hazard and Medical Evaluation of 6 patients with neurotoxicity associated with occupational exposure to 1-BP. Case series and environmental evaluation. Six workers, 1 male and 5 female, were exposed to high ambient 1-BP concentrations while employed in a golf club cleaning factory. 1-BP was identified in the bulk solvent sample used by the workers and confirmed the workers' daily occupational exposure to 1-BP for 3-10 months. The major presenting symptoms were tingling pain, soreness in lower extremities, and paresthesia. N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys), a 1-BP metabolite, was identified by LC/MS/MS in the urine (0.171-1.74 mg/g-Cr) of these workers 5-26 days following 1-BP exposure. DISCUSSION AND CONCLUSION: An occupational outbreak of 1-BP poisoning occurred as a result of recurrent power outages, condenser, and exhaust fans malfunction, and inadequate personal protection. Occupational exposure to 1-BP may result in peripheral neuropathy as well as adverse CNS effects. Urine AcPrCys may be a specific biomarker for 1-BP exposure. PMID- 26161840 TI - Serotonin syndrome precipitated by sertraline and discontinuation of clozapine. PMID- 26161841 TI - Single Molecules Trapped by Dynamic Inhomogeneous Temperature Fields. AB - We demonstrate a single molecule trapping concept that modulates the actual driving force of Brownian motion--the temperature. By spatially and temporally varying the temperature at a plasmonic nanostructure, thermodiffusive drifts are induced that are used to trap single nano-objects. A feedback controlled switching of local temperature fields allows us to confine the motion of a single DNA molecule for minutes and tailoring complex effective trapping potentials. This new type of thermophoretic microbeaker even provides control over a well defined number of single molecules and is scalable to large arrays of trapping structures. PMID- 26161842 TI - Gender-Based Violence and HIV in Rwanda: Respecting Women's Voices. PMID- 26161843 TI - Ionic Liquid Films at the Water-Air Interface: Langmuir Isotherms of Tetra alkylphosphonium-Based Ionic Liquids. AB - The behavior of ionic liquids trihexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide and trihexyl(tetradecyl)phosphonium dicyanamide, [P6 6 6 14][Ntf2] and [P6 6 6 14][N(CN)2], respectively, at the water-air interface was investigated using the Langmuir trough technique. The obtained surface pressure versus mean molecular area (MMA) isotherms, pi-A, and surface potential versus MMA isotherms, DeltaV-A, show distinct interfacial behavior between the two systems. The results were interpreted at a molecular level using molecular dynamics simulations: the different compression regimes along the [P6 6 6 14][Ntf2] isotherm correspond to the self-organization of the ions at the water surface into compact and planar monolayers that coalesce at an MMA value of ca. 1.85 nm(2)/ion pair to form an expanded liquidlike layer. Upon further compression, the monolayer collapses at around 1.2 nm(2)/ion pair to yield a progressively thicker and less organized layer. These transitions are much more subdued in the [P6 6 6 14][N(CN)2] system because of the more hydrophilic nature of the dicyanamide anion. The numerical density profiles obtained from the MD simulation trajectories are also able to emphasize the very unusual packing of the four long alkyl side chains of the cation above and below the ionic layer that forms at the water surface. Such a distribution is also different for the two studied systems during the different compression regimes. PMID- 26161844 TI - A Three-Factor Cancer-Related Mental Condition Model and Its Relationship With Cancer Information Use, Cancer Information Avoidance, and Screening Intention. AB - Cancer-related affect and cognition, such as cancer fear, cancer worry, and cancer risk perception, are important predictors of cancer prevention and communication behaviors. However, they have not been clearly conceptualized in cancer communication literature, and in particular, the role of affect (i.e., cancer fear) in cancer prevention and communication has not been fully investigated. The present study developed a 3-factor cancer-related mental condition model encompassing affective (cancer fear), cognitive (cancer risk perception), and affective-cognitive (cancer worry) conditions. Two studies were conducted. Study 1 developed the model with Sample 1 (U.S. undergraduates, N = 309), and subsequently validated the model with Sample 2 (Korean general population, ages 40 years or older, N = 1,130). Study 2, using Sample 2, tested the model's relationship with cancer information use, cancer information avoidance, and screening intention. While Sample 1 participants were asked about cancer in general, Sample 2 participants were asked specifically about stomach cancer. Thus, the model derived from the specific sample in a general context was confirmed via the general sample in a specific context. The results showed that both cancer worry and cancer risk perception are positively associated with cancer information use and screening intention, but they are negatively associated with cancer information avoidance. Cancer fear was positively associated with cancer information use, but it was also positively related to cancer information avoidance. Moreover, cancer fear was negatively associated with screening intention. Although the three components of the model are positively related to one another, they function differently in the cancer context. PMID- 26161845 TI - p-Type Transparent Conducting Oxide/n-Type Semiconductor Heterojunctions for Efficient and Stable Solar Water Oxidation. AB - Achieving stable operation of photoanodes used as components of solar water splitting devices is critical to realizing the promise of this renewable energy technology. It is shown that p-type transparent conducting oxides (p-TCOs) can function both as a selective hole contact and corrosion protection layer for photoanodes used in light-driven water oxidation. Using NiCo2O4 as the p-TCO and n-type Si as a prototypical light absorber, a rectifying heterojunction capable of light driven water oxidation was created. By placing the charge separating junction in the Si using a np(+) structure and by incorporating a highly active heterogeneous Ni-Fe oxygen evolution catalyst, efficient light-driven water oxidation can be achieved. In this structure, oxygen evolution under AM1.5G illumination occurs at 0.95 V vs RHE, and the current density at the reversible potential for water oxidation (1.23 V vs RHE) is >25 mA cm(-2). Stable operation was confirmed by observing a constant current density over 72 h and by sensitive measurements of corrosion products in the electrolyte. In situ Raman spectroscopy was employed to investigate structural transformation of NiCo2O4 during electrochemical oxidation. The interface between the light absorber and p-TCO is crucial to produce selective hole conduction to the surface under illumination. For example, annealing to produce more crystalline NiCo2O4 produces only small changes in its hole conductivity, while a thicker SiOx layer is formed at the n Si/p-NiCo2O4 interface, greatly reducing the PEC performance. The generality of the p-TCO protection approach is demonstrated by multihour, stable, water oxidation with n-InP/p-NiCo2O4 heterojunction photoanodes. PMID- 26161846 TI - Corrigendum: Single Molecule Investigation of Ag+ Interactions with Single Cytosine-, Methylcytosine- and Hydroxymethylcytosine-Cytosine Mismatches in a Nanopore. PMID- 26161847 TI - Homogeneous Gold-Catalyzed Glycosylations in Continuous Flow. AB - The use of versatile alkynyl-building blocks that are activated by gold(I) catalysis is demonstrated to efficiently generate a variety of glycosides in continuous flow. The application of a continuous flow setting to gold(I) catalyzed glycosylations enables very short reaction times and excellent control of the reaction conditions. PMID- 26161849 TI - Orthogonally Protected Furanoid Sugar Diamino Acids for Solid-Phase Synthesis of Oligosaccharide Mimetics. AB - Sugar diamino acids (SDAs), which differ from the widely used sugar amino acids in the presence of a second amino group connected to the carbohydrate core, share structural features of both amino acids and carbohydrates. They can be used for the preparation of linear and branched amide-linked oligosaccharide mimetics. Such oligomers carry free amino groups, which are positively charged at neutral pH, in a spatially defined way and, thus, represent a potential class of aminoglycoside mimetics. We report here the first examples of orthogonally protected furanoid SDAs and their use in solid-phase synthesis. Starting from d glucose, we developed a divergent synthetic route to three derivatives of 3,5 diamino-3,5-dideoxy-d-ribofuranose. These building blocks are compatible with solid-phase peptide synthesis following the 9-fluorenylmethoxycarbonyl (Fmoc) strategy, which we demonstrate by the synthesis of an SDA tetramer. PMID- 26161848 TI - Heme Stabilization of alpha-Synuclein Oligomers during Amyloid Fibril Formation. AB - alpha-Synuclein (alphaSyn), which forms amyloid fibrils, is linked to the neuronal pathology of Parkinson's disease, as it is the major fibrillar component of Lewy bodies, the inclusions that are characteristic of the disease. Oligomeric structures, common to many neurodegenerative disease-related proteins, may in fact be the primary toxic species, while the amyloid fibrils exist either as a less toxic dead-end species or even as a beneficial mechanism for clearing damaged proteins. To alter the progression of the aggregation and gain insights into the prefibrillar structures, we determined the effect of heme on alphaSyn oligomerization by several different techniques, including native (nondenaturing) polyacrylamide gel electrophoresis, thioflavin T fluorescence, transmission electron microscopy, atomic force microscopy, circular dichroism, and membrane permeation using a calcein release assay. During aggregation, heme is able to bind the alphaSyn in a specific fashion, stabilizing distinct oligomeric conformations and promoting the formation of alphaSyn into annular structures, thereby delaying and/or inhibiting the fibrillation process. These results indicate that heme may play a regulatory role in the progression of Parkinson's disease; in addition, they provide insights into how the aggregation process may be altered, which may be applicable to the understanding of many neurodegenerative diseases. PMID- 26161850 TI - Agreement between Myocardial Infarction Patients and Their Spouses on Reporting of Data on 82 Cardiovascular Risk Exposures. AB - BACKGROUND: The validity of exposure data collected from proxy respondents of myocardial infarction patients has scarcely been studied. We assessed the level of disagreement between myocardial infarction patients and their spouses with respect to the reporting of the patient's cardiovascular risk exposures. METHODS: Within the frame of the Stockholm Heart Epidemiology Program (SHEEP), a case control study of risk factors of myocardial infarction performed in Stockholm county 1992-1994, a subset of 327 first time myocardial infarction cases aged 45 70 who survived >28 days after the event and who co-habited with a spouse or common-law spouse (proxy) were identified between 1993-04-05 and 1993-12-31. Among these, 243 cases participated along with their respective proxy in the present study. Control individuals, matched to cases by age, sex and residential area were also included (n = 243). Data were collected using questionnaires. Using conditional logistic regression we calculated for each of 82 exposures the odds ratio based on information collected from 1) myocardial infarction cases and controls [odds ratio A] and 2) proxies and the same set of controls [odds ratio B]. Disagreement was measured by calculating the ratio between odds ratio B and odds ratio A with 95% confidence intervals (CI) calculated using resampling bootstrap. RESULTS: For the vast majority of the exposures considered including diet, smoking, education, work-related stress, and family history of CVD, there was no statistically significant disagreement between myocardial infarction patients and proxies (n = 243 pairs). However, leisure time physical inactivity (proxy bias = 1.59, 95% CI 1.05-3.57) was overestimated by spouses compared to myocardial infarction patients. A few other exposures including some sleep related problems and work-related issues also showed disagreement. CONCLUSIONS: Myocardial infarction patients and their spouses similarly reported data on a wide range of exposures including the majority of the traditional cardiovascular risk factors, leisure time physical inactivity being an exception. PMID- 26161851 TI - Strategic Adaptation to Task Characteristics, Incentives, and Individual Differences in Dual-Tasking. AB - We investigate how good people are at multitasking by comparing behavior to a prediction of the optimal strategy for dividing attention between two concurrent tasks. In our experiment, 24 participants had to interleave entering digits on a keyboard with controlling a randomly moving cursor with a joystick. The difficulty of the tracking task was systematically varied as a within-subjects factor. Participants were also exposed to different explicit reward functions that varied the relative importance of the tracking task relative to the typing task (between-subjects). Results demonstrate that these changes in task characteristics and monetary incentives, together with individual differences in typing ability, influenced how participants choose to interleave tasks. This change in strategy then affected their performance on each task. A computational cognitive model was used to predict performance for a wide set of alternative strategies for how participants might have possibly interleaved tasks. This allowed for predictions of optimal performance to be derived, given the constraints placed on performance by the task and cognition. A comparison of human behavior with the predicted optimal strategy shows that participants behaved near optimally. Our findings have implications for the design and evaluation of technology for multitasking situations, as consideration should be given to the characteristics of the task, but also to how different users might use technology depending on their individual characteristics and their priorities. PMID- 26161853 TI - Identifying the Role of Common Interests in Online User Trust Formation. AB - Despite enormous recent efforts in detecting the mechanism of the social relation formation in online social systems, the underlying rules between the common interests and social relations are still under dispute. Do online users befriend others who have similar tastes, or do their tastes become more similar after they become friends? In this paper, we investigate the correlation between online user trust formation and their common interests, measured by the overlap rate rho and taste similarity theta respectively. The trust relation creation time is set as the zero timestamp. The statistical results before and after the trust formation for an online network, namely Epinions, show that, the overlap rate rho increases greatly before the trust formation, while it would increase smoothly after the creation of the trust relation. Comparing with the empirical results, two null models are presented by shuffling the temporal behaviors of online users, which suggests that the accumulation of the common interests can result in the trust formation. Furthermore, we investigate the taste similarity theta of the common interests, which can reflect the users' preference on their common interests. The empirical results show that the taste similarity theta is rapidly increased around the day when users trust the others. That is, the similar tastes on the common interests among users lead to the trust formation. Finally, we report that the user degree can also influence the effect of the taste similarity theta on user trust formation. This work may shed some light for deeply understanding the evolution mechanism of the online social systems. PMID- 26161852 TI - Insulin Regulates the Activity of the High-Affinity Choline Transporter CHT. AB - Studies in humans and animal models show that neuronal insulin resistance increases the risk of developing Alzheimer's Disease (AD), and that insulin treatment may promote memory function. Cholinergic neurons play a critical role in cognitive and attentional processing and their dysfunction early in AD pathology may promote the progression of AD pathology. Synthesis and release of the neurotransmitter acetylcholine (ACh) is closely linked to the activity of the high-affinity choline transporter protein (CHT), but the impact of insulin receptor signaling and neuronal insulin resistance on these aspects of cholinergic function are unknown. In this study, we used differentiated SH-SY5Y cells stably-expressing CHT proteins to study the effect of insulin signaling on CHT activity and function. We find that choline uptake activity measured after acute addition of 20 nM insulin is significantly lower in cells that were grown for 24 h in media containing insulin compared to cells grown in the absence of insulin. This coincides with loss of ability to increase phospho-Protein Kinase B (PKB)/Akt levels in response to acute insulin stimulation in the chronic insulin treated cells. Inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3 kinase) in cells significantly lowers phospho-PKB/Akt levels and decreases choline uptake activity. We show total internal reflection microscopy (TIRF) imaging of the dynamic movement of CHT proteins in live cells in response to depolarization and drug treatments. These data show that acute exposure of depolarized cells to insulin is coupled to transiently increased levels of CHT proteins at the cell surface, and that this is attenuated by chronic insulin exposure. Moreover, prolonged inhibition of PI3-kinase results in enhanced levels of CHT proteins at the cell surface by decreasing their rate of internalization. PMID- 26161854 TI - Corneal Regeneration by Deep Anterior Lamellar Keratoplasty (DALK) Using Decellularized Corneal Matrix. AB - The purpose of this study is to demonstrate the feasibility of DALK using a decellularized corneal matrix obtained by HHP methodology. Porcine corneas were hydrostatically pressurized at 980 MPa at 10 degrees C for 10 minutes to destroy the cells, followed by washing with EGM-2 medium to remove the cell debris. The HHP-treated corneas were stained with H-E to assess the efficacy of decellularization. The decellularized corneal matrix of 300 MUm thickness and 6.0 mm diameter was transplanted onto a 6.0 mm diameter keratectomy wound. The time course of regeneration on the decellularized corneal matrix was evaluated by haze grading score, fluorescein staining, and immunohistochemistry. H-E staining revealed that no cell nuclei were observed in the decellularized corneal matrix. The decellularized corneal matrices were opaque immediately after transplantation, but became completely transparent after 4 months. Fluorescein staining revealed that initial migration of epithelial cells over the grafts was slow, taking 3 months to completely cover the implant. Histological sections revealed that the implanted decellularized corneal matrix was completely integrated with the receptive rabbit cornea, and keratocytes infiltrated into the decellularized corneal matrix 6 months after transplantation. No inflammatory cells such as macrophages, or neovascularization, were observed during the implantation period. The decellularized corneal matrix improved corneal transparency, and remodelled the graft after being transplanted, demonstrating that the matrix obtained by HHP was a useful graft for corneal tissue regeneration. PMID- 26161855 TI - Temporal Overlap and Co-Occurrence in a Guild of Sub-Tropical Tephritid Fruit Flies. AB - Studies of community assembly have emphasized snapshot comparisons of spatially replicated samples from "natural" assemblages. Agro-ecosystems are characterized by relatively little habitat heterogeneity and no dispersal barriers for actively flying insects. Therefore, dynamic patterns of species segregation and aggregation are more likely to reflect the direct or indirect effects of species interactions. We studied the temporal organization of a guild of 21 congeneric species of Anastrepha that colonized fruit orchards in Monte Alegre do Sul, Sao Paulo, Brazil. This assemblage also included the introduced Mediterranean fruit fly Ceratitis capitata. One hundred six consecutive weekly censuses (11 Jan 2002 16 Jan 2004) of flies in guava, loquat, and peach orchards revealed a pattern of minimum abundance during the coldest months of each year (June and July) and a maximum abundance during periods of flowering and fruit ripening. Overall, phenological overlap was greater than expected by chance. However, conditioned on the pattern of seasonal abundances, temporal occurrence and abundance matrices exhibited patterns of significant species segregation and anti-nestedness. In each year, the 3 orchards contained a small number of species pairs that exhibited statistically significant temporal segregation or aggregation. Most aggregated and segregated pairs reflected seasonal shifts in species presences that were not related to variation in air temperature. Most of the significant pairwise associations involved C. capitata: 8 of the 11 segregated pairs and 2 of the 7 aggregated pairs. These results suggest that species interactions between introduced and native species can be an important determinant of species associations in agro-ecosystems. PMID- 26161856 TI - Correction: Structural Basis for the Inhibition of Helicobacter pylori alpha Carbonic Anhydrase by Sulfonamides. PMID- 26161857 TI - Next-Generation Sequencing Techniques Reveal that Genomic Imprinting Is Absent in Day-Old Gallus gallus domesticus Brains. AB - Genomic imprinting is a phenomenon characterized by parent-of-origin-specific gene expression. While widely documented in viviparous mammals and plants, imprinting in oviparous birds remains controversial. Because genomic imprinting is temporal- and tissue-specific, we investigated this phenomenon only in the brain tissues of 1-day-old chickens (Gallus gallus). We used next-generation sequencing technology to compare four transcriptomes pooled from 11 chickens, generated from reciprocally crossed families, to the DNA sequences of their parents. Candidate imprinted genes were then selected from these sequence alignments and subjected to verification experiments that excluded all but one SNP. Subsequent experiments performed with two new sets of reciprocally crossed families resulted in the exclusion of that candidate SNP as well. Attempts to find evidence of genomic imprinting from long non-coding RNAs yielded negative results. We therefore conclude that genomic imprinting is absent in the brains of 1-day-old chickens. However, due to the temporal and tissue specificity of imprinting, our results cannot be extended to all growth stages and tissue types. PMID- 26161858 TI - The Validity of Claims-Based Algorithms to Identify Serious Hypersensitivity Reactions and Osteonecrosis of the Jaw. AB - Validation of claims-based algorithms to identify serious hypersensitivity reactions and osteonecrosis of the jaw has not been performed in large osteoporosis populations. The objective of this project is to estimate the positive predictive value of the claims-based algorithms in older women with osteoporosis enrolled in Medicare. Using the 2006-2008 Medicare 5% sample data, we identified potential hypersensitivity and osteonecrosis of the jaw cases based on ICD-9 diagnosis codes. Potential hypersensitivity cases had a 995.0, 995.2, or 995.3 diagnosis code on emergency department or inpatient claims. Potential osteonecrosis of the jaw cases had >=1 inpatient or outpatient physician claim with a 522.7, 526.4, 526.5, or 733.45 diagnosis code or >=2 claims of any type with a 526.9 diagnosis code. All retrieved records were redacted and reviewed by experts to determine case status: confirmed, not confirmed, or insufficient information. We calculated the positive predictive value as the number of confirmed cases divided by the total number of retrieved records with sufficient information. We requested 412 potential hypersensitivity and 304 potential osteonecrosis of the jaw records and received 174 (42%) and 84 (28%) records respectively. Of 84 potential osteonecrosis of the jaw cases, 6 were confirmed, resulting in a positive predictive value (95% CI) of 7.1% (2.7, 14.9). Of 174 retrieved potential hypersensitivity records, 95 were confirmed. After exclusion of 25 records with insufficient information for case determination, the overall positive predictive value (95% CI) for hypersensitivity reactions was 76.0% (67.5, 83.2). In a random sample of Medicare data, a claim-based algorithm to identify serious hypersensitivity reactions performed well. An algorithm for osteonecrosis of the jaw did not, partly due to the inclusion of diagnosis codes that are not specific for osteoporosis of the jaw. PMID- 26161859 TI - How Does a Divided Population Respond to Change? AB - Most studies on the response of socioeconomic systems to a sudden shift focus on long-term equilibria or end points. Such narrow focus forgoes many valuable insights. Here we examine the transient dynamics of regime shift on a divided population, exemplified by societies divided ideologically, politically, economically, or technologically. Replicator dynamics is used to investigate the complex transient dynamics of the population response. Though simple, our modeling approach exhibits a surprisingly rich and diverse array of dynamics. Our results highlight the critical roles played by diversity in strategies and the magnitude of the shift. Importantly, it allows for a variety of strategies to arise organically as an integral part of the transient dynamics--as opposed to an independent process--of population response to a regime shift, providing a link between the population's past and future diversity patterns. Several combinations of different populations' strategy distributions and shifts were systematically investigated. Such rich dynamics highlight the challenges of anticipating the response of a divided population to a change. The findings in this paper can potentially improve our understanding of a wide range of socio-ecological and technological transitions. PMID- 26161860 TI - The Effects of Habitat Type and Volcanic Eruptions on the Breeding Demography of Icelandic Whimbrels Numenius phaeopus. AB - Distinct preference of species for habitats is most often driven by long term differences in demographic rates between habitats. Estimating variation in those rates is key for developing successful conservation strategies. Stochastic events can interact with underlying variation in habitat quality in regulating demography but the opportunities to explore such interactions are rare. Whimbrels in Iceland show a strong preference for sparsely vegetated riverplains. Such habitats in Iceland face various threats, e.g., climate change, river regulation and spread of alien plant species. In this study we compared demographic parameters of breeding Whimbrels between riverplains and other habitats before, during and after volcanic eruption events to estimate the importance of the habitats for the species and the effect of ash deposit on breeding success. We found that an estimated minimum of 23% of the Icelandic population of Whimbrels and c. 10% of the world population of the species breed in riverplain habitats in Iceland. Whimbrels bred consistently at much higher densities in riverplain habitats than in other habitats and riverplains also had higher densities of pairs with fledglings although the proportion of successful breeders was similar between habitats. Predation by livestock may have had a considerable negative effect on breeding success on our study sites. Breeding was negatively affected by the volcanic activity, probably through the effects of ash on the invertebrate food supply, with breeding success being gradually worse closer to the eruption. Breeding success was equally affected by volcanism across habitats which differed in underlying habitat quality. This study gives an example of how populations can be regulated by factors which operate at different spatial scales, such as local variation in habitat quality and stochastic events which impact larger areas. PMID- 26161862 TI - The Association of Urbanicity with Cognitive Development at Five Years of Age in Preterm Children. AB - OBJECTIVE: To determine the association of urbanicity, defined as living in an urban area, with cognitive development at five years of age in preterm children who were free of any disabilities or neurodevelopmental delays. DESIGN: Prospective population-based cohort. SETTING: French regional Loire Infant Follow up Team (LIFT) network. PARTICIPANTS: Included in the study were 1738 surviving infants born between March 2003 and December 2008 before 35 weeks of gestational age. At two years of age, the children were free of any disabilities and neurodevelopmental delays and were living in the Pays de la Loire region from their birth to five years of age. MAIN OUTCOME MEASURES: The cognitive development at five years of age was evaluated with the Global School Adaptation score (GSA). The urbanicity of the residence for each child was classified into three groups: urban, quasi-rural, and rural area. RESULTS: Quantile regression approaches were used to identify a significant association between urbanicity and the GSA score at five years of age (adjusting for child and family characteristics). We found that the negative impact of urbanicity on the GSA score was more important for the lower quantile of the GSA scores. CONCLUSIONS: Urbanicity was significantly associated with cognitive neurodevelopment at five years of age in preterm children born before 35 weeks of gestation. Complementary results additionally suggest that this relation could be mediated at the residence level by a high socioeconomic deprivation level. If these results are confirmed, more personalized follow-ups could be developed for preterm children. Further studies are needed to finely identify the contextual characteristics of urbanicity that underlie this association. PMID- 26161861 TI - Vgamma9Vdelta2 T-Cell Polyfunctionality Is Differently Modulated in HAART-Treated HIV Patients according to CD4 T-Cell Count. AB - Alteration of gammadelta T-cell distribution and function in peripheral blood is among the earliest defects during HIV-infection. We asked whether the polyfunctional response could also be affected, and how this impairment could be associated to CD4 T-cell count. To this aim, we performed a cross-sectional study on HIV-infected individuals. In order to evaluate the polyfunctional Vgamma9Vdelta2 T-cell response after phosphoantigen-stimulation, we assessed the cytokine/chemokine production and cytotoxicity by flow-cytometry in HAART-treated HIV+ persons and healthy-donors. During HIV-infection Vgamma9Vdelta2 polyfunctional response quality is affected, since several Vgamma9Vdelta2 T-cell subsets resulted significantly lower in HIV+ patients in respect to healthy donors. Interestingly, we found a weak positive correlation between Vgamma9Vdelta2 T-cell-response and CD4 T-cell counts. By dividing the HIV+ patients according to CD4 T-cell count, we found that Low-CD4 patients expressed a lower number of two Vgamma9Vdelta2 T-cell subsets expressing MIP-1beta in different combinations with other molecules (CD107a/IFNgamma) in respect to High CD4 individuals. Our results show that the Vgamma9Vdelta2 T-cell-response quality in Low-CD4 patients is specifically affected, suggesting a direct link between innate Vgamma9Vdelta2 T-cells and CD4 T-cell count. These findings suggest that Vgamma9Vdelta2 T-cell quality may be indirectly influenced by HAART therapy and could be included in a new therapeutical strategy which would perform an important role in fighting HIV infection. PMID- 26161863 TI - Preferential Elimination of Older Erythrocytes in Circulation and Depressed Bone Marrow Erythropoietic Activity Contribute to Cadmium Induced Anemia in Mice. AB - Feeding cadmium chloride (50 or 1000 ppm CdCl2 in drinking water, ad libitum) to C57BL/6 mice resulted in a significant and sustained fall in blood erythrocyte count and hemoglobin levels that started 4 and 3 weeks after the start of 50 and 1000 ppm cadmium doses respectively. A transient yet significant reticulocytosis occurred during the first 4 weeks of cadmium treatment. Using the recently developed double in vivo biotinylation (DIB) technique, turnover of erythrocyte cohorts of different age groups was simultaneously monitored in control and cadmium treated mice. A significant accumulation of younger erythrocytes and a concomitant decline in the relative proportions of older erythrocytes in circulation was observed in both 50 and 1000 ppm cadmium groups indicating that older erythrocytes were preferentially eliminated in cadmium induced anemia. A significant increase in the erythropoietin levels in plasma was seen in mice exposed to 1000 ppm cadmium. Levels of inflammatory cytokines (IL1A, IL6, TNFalpha, IFNgamma) were however not significantly altered in cadmium treated mice. A significant increase in cellular levels of reactive oxygen species (ROS) was observed in older erythrocytes in circulation but not in younger erythrocytes. Erythropoietic activity in the bone marrows and spleens of cadmium treated mice was examined by monitoring the relative proportion of cells belonging to the erythroid line of differentiation in these organs. Erythroid cells in bone marrow declined markedly (about 30%) in mice in the 1000 ppm cadmium group but the decline was not significant in the 50 ppm cadmium group. Cells representing various stages of erythroid differentiation in bone marrow and spleen were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Decline of erythroid cells was essentially confined to pro-erythroblast and erythroblast-A, along with a concurrent increase in the splenic erythroid population indicating a stress response. In short cadmium exposure causes preferential clearance of older erythrocytes from circulation along with a depressed erythropoietic activity at higher doses. PMID- 26161864 TI - Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible? AB - BACKGROUND: Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. METHODOLOGY/PRINCIPAL FINDINGS: Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). CONCLUSION: The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study. PMID- 26161866 TI - A Multiplatform Metabolomic Approach to the Basis of Antimonial Action and Resistance in Leishmania infantum. AB - There is a rising resistance against antimony drugs, the gold-standard for treatment until some years ago. That is a serious problem due to the paucity of drugs in current clinical use. In a research to reveal how these drugs affect the parasite during treatment and to unravel the underlying basis for their resistance, we have employed metabolomics to study treatment in Leishmania infantum promastigotes. This was accomplished first through the untargeted analysis of metabolic snapshots of treated and untreated parasites both resistant and responders, utilizing a multiplatform approach to give the widest as possible coverage of the metabolome, and additionally through novel monitoring of the origin of the detected alterations through a 13C traceability experiment. Our data stress a multi-target metabolic alteration with treatment, affecting in particular the cell redox system that is essential to cope with detoxification and biosynthetic processes. Additionally, relevant changes were noted in amino acid metabolism. Our results are in agreement with other authors studying other Leishmania species. PMID- 26161865 TI - Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice. AB - Bacopa monnieri extract has been implicated in the recovery of memory impairments due to various neurological disorders in animal models and humans. However, the precise molecular mechanism of the role of CDRI-08, a well characterized fraction of Bacopa monnieri extract, in recovery of the diabetes mellitus-induced memory impairments is not known. Here, we demonstrate that DM2 mice treated orally with lower dose of CDRI-08 (50- or 100 mg/kg BW) is able to significantly enhance spatial memory in STZ-DM2 mice and this is correlated with a significant decline in oxidative stress and up regulation of the AMPA receptor GluR2 subunit gene expression in the hippocampus. Treatment of DM2 mice with its higher dose (150 mg/kg BW or above) shows anti-diabetic effect in addition to its ability to recover the spatial memory impairment by reversing the DM2-induced elevated oxidative stress and decreased GluR2 subunit expression near to their values in normal and CDRI-08 treated control mice. Our results provide evidences towards molecular basis of the memory enhancing and anti diabetic role of the Bacopa monnieri extract in STZ-induced DM2 mice, which may have therapeutic implications. PMID- 26161867 TI - Caspase-Cleaved Tau Co-Localizes with Early Tangle Markers in the Human Vascular Dementia Brain. AB - Vascular dementia (VaD) is the second most common form of dementia in the United States and is characterized as a cerebral vessel vascular disease that leads to ischemic episodes. Whereas the relationship between caspase-cleaved tau and neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) has been previously described, whether caspase activation and cleavage of tau occurs in VaD is presently unknown. To investigate a potential role for caspase-cleaved tau in VaD, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing a well-characterized antibody that specifically detects caspase-cleaved tau truncated at Asp421. Application of this antibody (TauC3) revealed consistent labeling within NFTs, dystrophic neurites within plaque-rich regions and corpora amylacea (CA) in the human VaD brain. Labeling of CA by the TauC3 antibody was widespread throughout the hippocampus proper, was significantly higher compared to age matched controls, and co-localized with ubiquitin. Staining of the TauC3 antibody co-localized with MC-1, AT8, and PHF-1 within NFTs. Quantitative analysis indicated that roughly 90% of PHF-1-labeled NFTs contained caspase cleaved tau. In addition, we documented the presence of active caspase-3 within plaques, blood vessels and pretangle neurons that co-localized with TauC3. Collectively, these data support a role for the activation of caspase-3 and proteolytic cleavage of TauC3 in VaD providing further support for the involvement of this family of proteases in NFT pathology. PMID- 26161868 TI - Quantitative Proteomic Analysis of BHK-21 Cells Infected with Foot-and-Mouth Disease Virus Serotype Asia 1. AB - Stable isotope labeling with amino acids in cell culture (SILAC) was used to quantitatively study the host cell gene expression profile, in order to achieve an unbiased overview of the protein expression changes in BHK-21 cells infected with FMDV serotype Asia 1. The SILAC-based approach identified overall 2,141 proteins, 153 of which showed significant alteration in the expression level 6 h post FMDV infection (57 up-regulated and 96 down-regulated). Among these proteins, six cellular proteins, including three down-regulated (VPS28, PKR, EVI5) and three up-regulated (LYPLA1, SEC62 and DARs), were selected according to the significance of the changes and/or the relationship with PKR. The expression level and pattern of the selected proteins were validated by immunoblotting and confocal microscopy. Furthermore, the functions of these cellular proteins were assessed by small interfering RNA-mediated depletion, and their functional importance in the replication of FMDV was demonstrated by western blot, reverse transcript PCR (RT-PCR) and 50% Tissue Culture Infective Dose (TCID50). The results suggest that FMDV infection may have effects on the expression of specific cellular proteins to create more favorable conditions for FMDV infection. This study provides novel data that can be utilized to understand the interactions between FMDV and the host cell. PMID- 26161869 TI - Implantable Self-Powered Low-Level Laser Cure System for Mouse Embryonic Osteoblasts' Proliferation and Differentiation. AB - Bone remodeling or orthodontic treatment is usually a long-term process. It is highly desirable to speed up the process for effective medical treatment. In this work, a self-powered low-level laser cure system for osteogenesis is developed using the power generated by the triboelectric nanogenerator. It is found that the system significantly accelerated the mouse embryonic osteoblasts' proliferation and differentiation, which is essential for bone and tooth healing. The system is further demonstrated to be driven by a living creature's motions, such as human walking or a mouse's breathing, suggesting its practical use as a portable or implantable clinical cure for bone remodeling or orthodontic treatment. PMID- 26161870 TI - Limitations of Keratoplasty in China: A Survey Analysis. AB - PURPOSE: Each year, over 8,000 corneal transplantation surgeries are performed in China. Unlike developed countries, which have established standard requirements for operative experience for corneal specialists, little information exists on surgical training for keratoplasty in China. The aim of this study was to assess the keratoplasty experience of Chinese corneal specialists and to characterize their surgical patterns. METHODS: One hundred and twenty-one corneal specialists in 16 provinces (65 cities) in China were invited to complete an anonymous survey at the 2014 Chinese Corneal Society annual meeting, which consisted of questions with single or multiple-choice answers. Demographics, the number and type of keratoplasties performed, and the perceived limiting factors for performing keratoplasties were analyzed. RESULTS: An overwhelming 89% response rate was achieved. Of the 108 respondents, 76% worked in tertiary centers, and only 23% held a medical doctorate degree. Furthermore, 69% of the participants had received corneal fellowship training of less than one year. Only 71% were capable of keratoplasties. Among those doing keratoplasty, 68% performed less than 50 keratoplasties each year. Of the same group of keratoplasty surgeons, 88% of corneal specialists capable of keratoplasties had performed penetrating keratoplasties, 87% had performed lamellar keratoplasties, 12% had performed deep anterior lamellar keratoplasties, and 5% had performed Descemet's stripping endothelial keratoplasties. When questioned on the reasons for the low number of keratoplasties performed in China, the respondents deemed the following factors most important: lack of surgical training (71%), a shortage of donor supply (52%), and a lack of curricula (42%). A multivariate logistic regression analysis showed that corneal transplantation capabilities are significantly associated with responders' education levels and training time. CONCLUSION: Keratoplasty surgery experience is suboptimal for Chinese corneal specialists. Penetrating and lamellar keratoplasties are the preferred surgical patterns. Our findings raise concerns about the adequacy of keratoplasty training in China. PMID- 26161875 TI - Hybrid Molecule-Nanocrystal Photon Upconversion Across the Visible and Near Infrared. AB - The ability to upconvert two low energy photons into one high energy photon has potential applications in solar energy, biological imaging, and data storage. In this Letter, CdSe and PbSe semiconductor nanocrystals are combined with molecular emitters (diphenylanthracene and rubrene) to upconvert photons in both the visible and the near-infrared spectral regions. Absorption of low energy photons by the nanocrystals is followed by energy transfer to the molecular triplet states, which then undergo triplet-triplet annihilation to create high energy singlet states that emit upconverted light. By using conjugated organic ligands on the CdSe nanocrystals to form an energy cascade, the upconversion process could be enhanced by up to 3 orders of magnitude. The use of different combinations of nanocrystals and emitters shows that this platform has great flexibility in the choice of both excitation and emission wavelengths. PMID- 26161871 TI - Peripheral Endothelial (Dys)Function, Arterial Stiffness and Carotid Intima-Media Thickness in Patients after Kawasaki Disease: A Systematic Review and Meta Analyses. AB - BACKGROUND: Kawasaki disease (KD) is a systemic pediatric vasculitis. Its main complication is the development of coronary arterial aneurysms (CAA), causing an increased risk for ischemia and myocardial infarction. It is unclear whether KD patients, apart from the presence of CAA, have an increased cardiovascular disease (CVD) risk due to the previous systemic vasculitis. The aim of this study was to systematically review and meta-analyse the literature regarding surrogate markers for CVD risk in KD patients. METHODS: Medline and Embase were searched for articles comparing endothelial dysfunction (flow-mediated dilation, nitroglycerin-mediated dilation and peripheral arterial tonometry), vascular stiffness (stiffness index, pulse wave velocity) and carotid intima-media thickness (cIMT) between patients and controls. Two investigators assessed the articles for eligibility and evaluated quality. RESULTS: Thirty studies were included. For all outcomes, moderate to high heterogeneity between studies was found. Most studies reported a decreased flow-mediated dilation in the whole KD- and CAA-positive group compared to controls, while data on CAA-negative patients were conflicting. The stiffness index was increased in the majority of studies evaluating the whole KD- and CAA-positive group, but not in most studies on CAA negative patients. Mean cIMT was neither significantly increased in the whole KD group nor in the CAA-positive group nor in most studies studying CAA-negative patients. Studies measuring maximum cIMT were conflicting. CONCLUSION: Literature suggests that surrogate markers for CVD risk in KD patients are increased in CAA positive but not in CAA-negative patients. This may indicate that CAA-positive patients should be monitored for CVD in later life. The results of this review have to be interpreted with care due to substantial heterogeneity between studies and methodological limitations, as well as the lack of long-term follow-up studies. PMID- 26161876 TI - Smoking-Associated Disordering of the Airway Basal Stem/Progenitor Cell Metabotype. AB - The airway epithelium is a complex pseudostratified multicellular layer lining the tracheobronchial tree, functioning as the primary defense against inhaled environmental contaminants. The major cell types of the airway epithelium include basal, intermediate columnar, ciliated, and secretory. Basal cells (BCs) are the proliferating stem/progenitor population that differentiate into the other specialized cell types of the airway epithelium during normal turnover and repair. Given that cigarette smoke delivers thousands of xenobiotics and high levels of reactive molecules to the lung epithelial surface, we hypothesized that cigarette smoke broadly perturbs BC metabolism. To test this hypothesis, primary airway BCs were isolated from healthy nonsmokers (n = 11) and healthy smokers (n = 7) and assessed by global metabolic profiling by liquid chromatography-mass spectrometry. The analysis identified 52 significant metabolites in BCs differentially expressed between smokers and nonsmokers (P < 0.05). These changes included metabolites associated with redox pathways, energy production, and inflammatory processes. Notably, BCs from smokers exhibited altered levels of the key enzyme cofactors/substrates nicotinamide adenine dinucleotide, flavin adenine dinucleotide, acetyl coenzyme A, and membrane phospholipid levels. Consistent with the high burden of oxidants in cigarette smoke, glutathione levels were diminished, whereas 3-nitrotyrosine levels were increased, suggesting that protection of airway epithelial cells against oxidative and nitrosative stress is significantly compromised in smoker BCs. It is likely that this altered metabotype is a reflection of, and likely contributes to, the disordered biology of airway BCs consequent to the stress cigarette smoking puts on the airway epithelium. PMID- 26161879 TI - From the Editor: Thank You and Good Bye. PMID- 26161880 TI - My First Science Fair. PMID- 26161878 TI - Shape Optimization for Additive Manufacturing of Removable Partial Dentures--A New Paradigm for Prosthetic CAD/CAM. AB - With ever-growing aging population and demand for denture treatments, pressure induced mucosa lesion and residual ridge resorption remain main sources of clinical complications. Conventional denture design and fabrication are challenged for its labor and experience intensity, urgently necessitating an automatic procedure. This study aims to develop a fully automatic procedure enabling shape optimization and additive manufacturing of removable partial dentures (RPD), to maximize the uniformity of contact pressure distribution on the mucosa, thereby reducing associated clinical complications. A 3D heterogeneous finite element (FE) model was constructed from CT scan, and the critical tissue of mucosa was modeled as a hyperelastic material from in vivo clinical data. A contact shape optimization algorithm was developed based on the bi-directional evolutionary structural optimization (BESO) technique. Both initial and optimized dentures were prototyped by 3D printing technology and evaluated with in vitro tests. Through the optimization, the peak contact pressure was reduced by 70%, and the uniformity was improved by 63%. In vitro tests verified the effectiveness of this procedure, and the hydrostatic pressure induced in the mucosa is well below clinical pressure-pain thresholds (PPT), potentially lessening risk of residual ridge resorption. This proposed computational optimization and additive fabrication procedure provides a novel method for fast denture design and adjustment at low cost, with quantitative guidelines and computer aided design and manufacturing (CAD/CAM) for a specific patient. The integration of digitalized modeling, computational optimization, and free-form fabrication enables more efficient clinical adaptation. The customized optimal denture design is expected to minimize pain/discomfort and potentially reduce long-term residual ridge resorption. PMID- 26161877 TI - Mutagenesis Screen Identifies agtpbp1 and eps15L1 as Essential for T lymphocyte Development in Zebrafish. AB - Genetic screens are a powerful tool to discover genes that are important in immune cell development and function. The evolutionarily conserved development of lymphoid cells paired with the genetic tractability of zebrafish make this a powerful model system for this purpose. We used a Tol2-based gene-breaking transposon to induce mutations in the zebrafish (Danio rerio, AB strain) genome, which served the dual purpose of fluorescently tagging cells and tissues that express the disrupted gene and provided a means of identifying the disrupted gene. We identified 12 lines in which hematopoietic tissues expressed green fluorescent protein (GFP) during embryonic development, as detected by microscopy. Subsequent analysis of young adult fish, using a novel approach in which single cell suspensions of whole fish were analyzed by flow cytometry, revealed that 8 of these lines also exhibited GFP expression in young adult cells. An additional 15 lines that did not have embryonic GFP+ hematopoietic tissue by microscopy, nevertheless exhibited GFP+ cells in young adults. RT-PCR analysis of purified GFP+ populations for expression of T and B cell-specific markers identified 18 lines in which T and/or B cells were fluorescently tagged at 6 weeks of age. As transposon insertion is expected to cause gene disruption, these lines can be used to assess the requirement for the disrupted genes in immune cell development. Focusing on the lines with embryonic GFP+ hematopoietic tissue, we identified three lines in which homozygous mutants exhibited impaired T cell development at 6 days of age. In two of the lines we identified the disrupted genes, agtpbp1 and eps15L1. Morpholino-mediated knockdown of these genes mimicked the T cell defects in the corresponding mutant embryos, demonstrating the previously unrecognized, essential roles of agtpbp1 and eps15L1 in T cell development. PMID- 26161881 TI - The Influence of Age-Related Cues on Health and Longevity. AB - Environmental cues that signal aging may directly and indirectly prime diminished capacity. Similarly, the absence of these cues may prime improved health. The authors investigated the effects of age cues on health and longevity in five very different settings. The findings include the following: First, women who think they look younger after having their hair colored/cut show a decrease in blood pressure and appear younger in photographs (in which their hair is cropped out) to independent raters. Second, clothing is an age-related cue. Uniforms eliminate these age-related cues: Those who wear work uniforms have lower morbidity than do those who earn the same amount of money and do not wear work uniforms. Third, baldness cues old age. Men who bald prematurely see an older self and therefore age faster: Prematurely bald men have an excess risk of getting prostate cancer and coronary heart disease than do men who do not prematurely bald. Fourth, women who bear children later in life are surrounded by younger age-related cues: Older mothers have a longer life expectancy than do women who bear children earlier in life. Last, large spousal age differences result in age-incongruent cues: Younger spouses live shorter lives and older spouses live longer lives than do controls. PMID- 26161882 TI - Collaborative Memory: Cognitive Research and Theory. AB - People often form and retrieve memories in the company of others. Yet, nearly 125 years of cognitive research on learning and memory has mainly focused on individuals working in isolation. Although important topics such as eyewitness memory and autobiographical memory have evaluated social influences, a study of group memory has progressed mainly within the provinces of history, anthropology, sociology, and social psychology. In this context, the recent surge in research on the cognitive basis of collaborative memory marks an important conceptual departure. As a first aim, we review these empirical and theoretical advances on the nature and influence of collaborative memory. Effects of collaboration are counterintuitive because individuals remember less when recalling in groups. Collaboration can also lead to forgetting and increase memory errors. Conversely, collaboration can also improve memory under proper conditions. As a second aim, we propose an overarching theoretical framework that specifies the cognitive mechanisms associated with the costs and benefits of collaboration on memory. A study of the reciprocal influences of the group and the individual on memory processes naturally draws upon several disciplines. Our aim is to elucidate the cognitive components of this complex phenomenon and situate this analysis within a broader interdisciplinary perspective. PMID- 26161883 TI - Structural Models and the Art of Approximation. AB - Structural equation models have provided a seemingly rigorous method for investigating causal relations in nonexperimental data in the presence of measurement error or multiple measures of putative causes or effects. Methods have been developed for fitting these very complex models globally and obtaining global fit statistics or global measures of their approximation to sample data. Structural equation models are idealizations that can serve only as approximations to real multivariate data. Further, these models are multidimensional, and the approximation is itself multidimensional. Tests of "significance" and global indices of approximation do not provide an adequate basis for judging the acceptability of the approximation. Standard applications of structural models use a composite of two models-a measurement (path) model and a path (causal) model. Separate analyses of the measurement model and the path model provide an informed judgment, whereas the composite global analysis can easily yield unreasonable conclusions. Separating the component models enables a careful assessment of the actual constraints implied by the path model, using recently developed methods. An empirical example shows how the conventional global treatment yields unacceptable conclusions. PMID- 26161884 TI - Sexual Orientation Differences as Deficits: Science and Stigma in the History of American Psychology. AB - This article briefly describes how psychology, psychiatry, and the mental health professions (here collectively referred to as Psychology) treated sexual orientation differences as deficits for much of the 20th century, as well as some of the negative consequences that practice had for sexual minorities. The 1970s witnessed a remarkable turnaround when the American Psychiatric Association removed homosexuality from the Diagnostic and Statistical Manual of Mental Disorders and the American Psychological Association called for psychologists to work to remove the stigma historically associated with homosexuality. This history illustrates not only how cultural institutions play a central role in legitimating stigma, but also how they can recognize their own complicity in this process and work effectively to undo its harmful effects. It is argued that Psychology still has an important role to play in challenging the differences-as deficits model in contemporary policy debates. PMID- 26161885 TI - I'm White and You're Not: The Value of Unraveling Ethnocentric Science. AB - Whether motivated by racist intent, ethnocentric arrogance, or data analytic myopia, research that systematically stigmatizes specific human groups is destructive. The racist assumptions of the inferiority of African culture and persons of African descent have contributed substantially to stigmatizing beliefs about African Americans. This article presents historical examples of several kinds of motivated or myopic theoretical and empirical projects that stigmatize African Americans and examples of how an examination of culture and social context may alleviate these problems. A discussion of ways to diversify psychological science includes diversifying those who do it, broadening the cultural perspectives and problems from which psychological concepts emanate (particularly in the United States), and formalizing diversity science as a system of theoretical and empirical research. PMID- 26161886 TI - Culture and the Home-Field Disadvantage. AB - The home-field disadvantage refers to the disadvantage inherent in research that takes a particular cultural group as the starting point or standard for research, including cross-cultural research. We argue that home-field status is a serious handicap that often pushes researchers toward deficit thinking, however good the researchers' intentions may be. In this article, we aim to make this home-field bias more explicit and, in doing so, more avoidable. We discuss three often overlooked disadvantages that result from this home-field status: the problem of marked versus unmarked culture, the problem of homogenous versus heterogeneous culture, and the problem of regression toward the mean. We also recommend four interventions researchers can apply to avoid the home-field disadvantage or, at the least, attenuate its deleterious effects. PMID- 26161887 TI - Neuroimaging: Voodoo, New Phrenology, or Scientific Breakthrough? Introduction to Special Section on fMRI. PMID- 26161888 TI - Brain Imaging, Cognitive Processes, and Brain Networks. AB - The recent, rapid expansion of the application of neuroimaging techniques to a broad variety of questions about the structure and function of mind and brain has led to much necessary and often critical introspection about what these techniques can actually tell us about cognitive processes. In this article, we attempt to place neuroimaging within the broader context of the cognitive neuroscience approach, which emphasizes the benefits of converging methodologies for understanding cognition and how it is supported by the functioning of the brain. Our arguments for what neuroimaging has to offer are supported by two specific examples from research on memory that, we believe, show how neuroimaging data have provided unique insights not only into brain organization, but also into the organization of the mind. PMID- 26161889 TI - The Appeal of the Brain in the Popular Press. AB - Since the advent of human neuroimaging, and of functional magnetic resonance imaging (fMRI) in particular, the popular press has shown an increasing interest in brain-related findings. In this article, I explore possible reasons behind this interest, including recent data suggesting that people find brain images and neuroscience language more convincing than results that make no reference to the brain (McCabe & Castel, 2008; Weisberg, Keil, Goodstein, Rawson, & Gray, 2008). I suggest that part of the allure of these data are the deceptively simply messages they afford, as well as general, but sometimes misguided, confidence in biological data. In addition to cataloging some misunderstandings by the press and public, I highlight the responsibilities of the research scientist in carefully conveying their work to the general public. PMID- 26161890 TI - Bridging Psychological and Biological Science: The Good, Bad, and Ugly. AB - Revolution or the new phrenology-the advent of functional neuroimaging has led some psychologists to address issues of structure-function relations that only two decades ago would have been relegated to science fiction. Others, however, are skeptical of recent bridges between psychological and biological science and consider these advances as misguided and leading us astray. With any new advancement comes problems and pitfalls, and constructive criticisms help to sharpen the research program. Here I offer commentary on the state of the art and identify both advances and concerns in bridging psychological and biological science. PMID- 26161892 TI - What's in a Name? When It Comes to Terrorism and Counterterrorism, a Great Deal. PMID- 26161891 TI - What Should This Fight Be Called? Metaphors of Counterterrorism and Their Implications. AB - This monograph examines from a psychological perspective the use of metaphors in framing counterterrorism. Four major counterterrorism metaphors are considered, namely those of war, law enforcement, containment of a social epidemic, and a process of prejudice reduction. The war metaphor is as follows: Wars are fought by states; the enemy is thus an identifiable entity whose interests fundamentally oppose your own. The conflict is zero-sum-the outcome will be victory for one side or the other-and there is no compromise. The war metaphor is totalistic and extreme. Arguably, it was adopted in light of the immensity of damage and national hurt produced by the 9/11 attack. It has insinuated itself into the public discourse about counterterrorism, and it has guided policy, but it has also met challenges because of lack of fit and the availability of counteranalogies with different lessons of history. Some of the drawbacks of the war metaphor are addressable in the law enforcement metaphor of counterterrorism. Unlike war's special status and circumscribed duration, law enforcement is an ongoing concern that must compete for resources with other societal needs. A major advantage of law enforcement over warfare is its focused nature-targeting the actual terrorists, with less likelihood of injuring innocent parties. Yet despite its advantages, the law enforcement metaphor exhibits a partial mismatch with the realities of terrorism. Its complete and uncritical adoption may temporarily hamper terrorists' ability to launch attacks without substantially altering their motivation to do so. The public health epidemiological model was usefully applied to the epidemic of terror that followed the 9/11 attacks. It utilizes a partition between (a) an external agent, (b) a susceptible host, (c) an environment that brings them together, and (d) the vector that enables transmission of the disease. In the specific application to jihadist terrorism, the agent refers to the militant Islamist ideology, the susceptible host refers to radicalizable Muslim populations, the environment refers to conditions that promote the readiness to embrace such ideology, and the vectors are conduits whereby the ideology is propagated. The epidemiological metaphor has its own advantages over the war and law enforcement metaphors, but also limitations. Whereas the latter metaphors neglect the long-range process of ideological conversion and radicalization that creates terrorists, the epidemiological metaphor neglects the "here and now" of counterterrorism and the value of resolute strikes and intelligence-gathering activities needed to counter terrorists' concrete schemes and capabilities. Framing counterterrorism as the process of prejudice reduction addresses the interaction between two communities whose conflict may breed terrorism. This framing shifts the focus from a unilateral to a bilateral concern and acknowledges the contribution to intergroup tensions that the party targeted by terrorists may make. A major tool of prejudice reduction is the creation of positive contact between members of the conflicted groups. Efforts at prejudice reduction via positive contact need to take place in the context of a larger set of policies, such as those concerning immigration laws, educational programs, and foreign policy initiatives designed to augment the good-will-generating efforts of optimal-contact programs. For all its benefits, the prejudice-reduction framework is also not without its drawbacks. Specifically, the positive-contact notion highlights the benefits of mere human interaction; it disregards differences in ideological beliefs between the interacting parties, thereby neglecting an element that appears essential to producing their estrangement and reciprocal animosity. Too, like the epidemiological metaphor, the prejudice-reduction framing takes the long view, thereby neglecting the "here and now" of terrorism and the need to counter specific terrorist threats. Thus, each of the foregoing frameworks captures some aspects of counterterrorism's effects while neglecting others. Accordingly, an integrated approach to counterterrorism is called for, one that exploits the insights of each metaphor and avoids its pitfalls. Such an approach would maximize the likelihood of enlightened decision making concerning contemplated counterterrorist moves given the complex tradeoffs that each such move typically entails. PMID- 26161894 TI - Reversible Formation and Transmetalation of Schiff-Base Complexes in Subcomponent Self-Assembly Reactions. AB - Dinuclear complexes [Zn2(NS,NS)2] 3 and [Ni2(NS,NS)2] 6 bearing Schiff-base ligands featuring two NS donor groups were obtained in subcomponent self-assembly reactions using nickel or zinc as template metals. Several transmetalation reactions starting from 3 or 6 yielded the complexes [Pd2(NS,NS)2] 4 and [Co2(NS,NS)2] 5, and their molecular structures were determined by X-ray diffraction. Starting from the mononuclear complex [Ni(NS/NOH)2] 9 featuring a coordinated NS Schiff base and a free NOH Schiff base, completely reversible thermodynamically controlled imine bond formation was observed leading to complex [Ni2(NS,NS)2] 6 and the free Schiff -base ligand NOH,NOH 10. PMID- 26161893 TI - Flot-2 Expression Correlates with EGFR Levels and Poor Prognosis in Surgically Resected Non-Small Cell Lung Cancer. AB - We previously reported that expression of Flotillin 2 (Flot-2), a protein isolated from caveolae/lipid raft domains, increased significantly in nasopharyngeal carcinoma (NPC) compared with normal tissues. Signal transduction through epidermal growth factor receptors (EGFR) and Flot-2 play an important role in cancer development, but their precise role in lung cancer has not been investigated. In this study, we have investigated the correlation between the expression of Flot-2 and EGFR, which increase significantly in non-small cell lung cancer (NSCLC) patients (n=352) compared with non-cancer tissues. Additionally, patients with advanced stages of NSCLC had higher positive expression of Flot-2 and EGFR than patients with early stages. NSCLC patients with increased expression of Flot-2 and EGFR had significantly less overall survival rates than patients with less expression of Flot-2 and EGFR. Taken together, our data suggest that increased expression of Flot-2 and EGFR in NSCLC patients is inversely proportional to the disease prognosis and that increased expression of Flot-2 associated with increased EGFR may serve as a biomarker to predict poor disease prognosis. PMID- 26161895 TI - Interaction of Mean Temperature and Daily Fluctuation Influences Dengue Incidence in Dhaka, Bangladesh. AB - Local weather influences the transmission of the dengue virus. Most studies analyzing the relationship between dengue and climate are based on relatively coarse aggregate measures such as mean temperature. Here, we include both mean temperature and daily fluctuations in temperature in modelling dengue transmission in Dhaka, the capital of Bangladesh. We used a negative binomial generalized linear model, adjusted for rainfall, anomalies in sea surface temperature (an index for El Nino-Southern Oscillation), population density, the number of dengue cases in the previous month, and the long term temporal trend in dengue incidence. In addition to the significant associations of mean temperature and temperature fluctuation with dengue incidence, we found interaction of mean and temperature fluctuation significantly influences disease transmission at a lag of one month. High mean temperature with low fluctuation increases dengue incidence one month later. Besides temperature, dengue incidence was also influenced by sea surface temperature anomalies in the current and previous month, presumably as a consequence of concomitant anomalies in the annual rainfall cycle. Population density exerted a significant positive influence on dengue incidence indicating increasing risk of dengue in over-populated Dhaka. Understanding these complex relationships between climate, population, and dengue incidence will help inform outbreak prediction and control. PMID- 26161896 TI - Phylogeography in Galaxias maculatus (Jenyns, 1848) along Two Biogeographical Provinces in the Chilean Coast. AB - Major geologic and climatic changes during the Quaternary exerted a major role in shaping past and contemporary distribution of genetic diversity and structure of aquatic organisms in southern South America. In fact, the northern glacial limit along the Pacific coast, an area of major environmental changes in terms of topography, currents, and water salinity, represents a major biogeographic transition for marine and freshwater species. We used mitochondrial DNA sequences (D-loop) to investigate the consequences of Quaternary glacial cycles over the pattern of genetic diversity and structure of G. maculatus (Pisces: Galaxiidae) along two biogeographical provinces in the Chilean coast. Extreme levels of genetic diversity and strong phylogeographic structure characterize the species suggesting a low amount of influence of the last glacial cycle over its demography. However, we recognized contrasting patterns of genetic diversity and structure between main biogeographical areas here analyzed. Along the Intermediate Area (38 degrees -41 degrees S) each estuarine population constitutes a different unit. In contrast, Magellanic populations (43 degrees -53 degrees S) exhibited low levels of genetic differentiation. Contrasting patterns of genetic diversity and structure recorded in the species between the analyzed biogeographic areas are consistent with the marked differences in abiotic factors (i.e., different coastal configurations, Quaternary glacial histories, and oceanographic regimes) and to inherent characteristics of the species (i.e., salt tolerance, physiology, and reproductive behavior). PMID- 26161898 TI - Structural Ordering and Charge Variation Induced by Cation Substitution in (Sr,Ca)AlSiN3:Eu Phosphor. AB - Nitride phosphors are suitable for white light-emitting diode applications. In this study, the structure of phosphor has been modified through cation substitution to induce charge variation and a rearrangement of neighboring nitride clusters, and consequently enhance its luminescent behavior. Substitution of Ca(2+) by Sr(2+) cations expanded the lattice volume and the bc plane, but shortened the distance between the layers along the a axis. Lattice distortion of the framework introduced high-coordination sites in the Sr/Eu centers and adequate space, thereby facilitating charge variation of activators under reduced atmosphere, as detected through X-ray absorption near-edge structure spectroscopy. As such, the photoluminescent intensity of the phosphors increased by more than 10% and a blue shift occurred. The microstructures of the samples were also analyzed using high-resolution transmission electron microscopy. Cation substitution induced a special change in the anion environment, as indicated in the solid-state Raman spectra. Moreover, typical ordering variations in the SiN4 and AlN4 clusters are generated in the lattice. Meanwhile, neighbor sequence of (Si/Al)N4 around the divalent centers were observed through solid-state nuclear magnetic resonance spectroscopy. The modified ordering distribution resulted in a rigid structure and improved the thermal quenching behavior. Thermal stability has been enhanced by 10% at 473 K when x = 0.9 in SrxCa0.993-xAlSiN3:Eu(2+)0.007 compared with that at x = 0. This study promotes the research of neighbor sequence for selective tetrahedral sites such as Li, Mg, Al, and Si coordinated by N atoms in contact with cation sites. PMID- 26161897 TI - The Harmonic Scalpel versus Conventional Hemostasis for Neck Dissection: A Meta Analysis of the Randomized Controlled Trials. AB - OBJECTIVE: Neck dissection is the most definitive and effective treatment for head and neck cancer. This systematic review aims to compare the efficacy and surgical outcomes of neck dissection between the harmonic scalpel and conventional surgical techniques and conduct a quantitative meta-analysis of the randomized trials. METHODS: Randomized controlled trials (RCTs) were identified from the major electronic databases (MEDLINE, EMBASE and Cochrane Library) using the keywords ''harmonic scalpel'' and ''neck dissection,'' and a quantitative meta-analysis was conducted. The operative time and intraoperative bleeding were the primary outcome measures, and other parameters assessed included the drainage fluid volume and length of hospital stay. RESULTS: Seven trials that met the inclusion criteria included 406 neck dissection cases (201 in the harmonic scalpel group). Compared with conventional surgical techniques, the HS group had an operative time that was significantly reduced by 29.3 minutes [mean difference: -29.29; 95% CI = (-44.26, -14.32); P=0.0001], a reduction in intraoperative bleeding by 141.1 milliliters [mean difference: -141.13; 95% CI = (-314.99, 32.73); P=0.11], and a reduction in drainage fluid volume by 64.9 milliliters [mean difference: -64.86; 95% CI = (-110.40, -19.32); P=0.005] , but it is not significant after removal of studies driving heterogeneity. There was no significant difference in the length of the hospital stay [mean difference: 0.21; 95% CI = (-0.48, 0.07); P=0.14]. CONCLUSION: This systematic review showed that using the harmonic scalpel for neck dissection significantly reduces the operative time and drainage fluid volume and that it is not associated with an increased length of hospital stay or perioperative complications. Therefore, the harmonic scalpel method is safe and effective for neck dissection. However, the statistical heterogeneity was high. Further studies are required to substantiate our findings. PMID- 26161899 TI - The Effect of Age on Listening Effort. AB - PURPOSE: The objective of this study was to investigate the effect of age on listening effort. METHOD: A dual-task paradigm was used to evaluate listening effort in different conditions of background noise. Sixty adults ranging in age from 20 to 77 years were included. A primary speech-recognition task and a secondary memory task were performed both separately and simultaneously. Multiple regression analyses were used to evaluate how age and hearing thresholds affect speech recognition and listening effort scores. RESULTS: Results of the multiple regression analyses showed that age is a significant determinant of listening effort, whereby listening effort increases with increasing age even when age related variance in speech recognition is partialled out. On the basis of the regression equations and the median score for listening effort, it was found that listening effort started to increase in the fourth decade of life. CONCLUSIONS: This study was a first exploration of listening effort from young to older adults and showed that, independent of hearing sensitivity, listening effort increases with age. To be more specific, there is a need to further investigate the cognitive functions important for speech communication while exploring their possible relationship with listening effort. PMID- 26161900 TI - Scanning and Filling: Ultra-Dense SNP Genotyping Combining Genotyping-By Sequencing, SNP Array and Whole-Genome Resequencing Data. AB - Genotyping-by-sequencing (GBS) represents a highly cost-effective high-throughput genotyping approach. By nature, however, GBS is subject to generating sizeable amounts of missing data and these will need to be imputed for many downstream analyses. The extent to which such missing data can be tolerated in calling SNPs has not been explored widely. In this work, we first explore the use of imputation to fill in missing genotypes in GBS datasets. Importantly, we use whole genome resequencing data to assess the accuracy of the imputed data. Using a panel of 301 soybean accessions, we show that over 62,000 SNPs could be called when tolerating up to 80% missing data, a five-fold increase over the number called when tolerating up to 20% missing data. At all levels of missing data examined (between 20% and 80%), the resulting SNP datasets were of uniformly high accuracy (96-98%). We then used imputation to combine complementary SNP datasets derived from GBS and a SNP array (SoySNP50K). We thus produced an enhanced dataset of >100,000 SNPs and the genotypes at the previously untyped loci were again imputed with a high level of accuracy (95%). Of the >4,000,000 SNPs identified through resequencing 23 accessions (among the 301 used in the GBS analysis), 1.4 million tag SNPs were used as a reference to impute this large set of SNPs on the entire panel of 301 accessions. These previously untyped loci could be imputed with around 90% accuracy. Finally, we used the 100K SNP dataset (GBS + SoySNP50K) to perform a GWAS on seed oil content within this collection of soybean accessions. Both the number of significant marker-trait associations and the peak significance levels were improved considerably using this enhanced catalog of SNPs relative to a smaller catalog resulting from GBS alone at <=20% missing data. Our results demonstrate that imputation can be used to fill in both missing genotypes and untyped loci with very high accuracy and that this leads to more powerful genetic analyses. PMID- 26161901 TI - 3-Monochloropropane-1,2-diol fatty acid esters in commercial deep-fat fried foods. AB - Levels of 3-monochloropropane-1,2-diol (3-MCPD) fatty acid esters were evaluated in commercial deep-fat fried foods from the Brazilian market using a GC-MS method preceded by acid-catalysed methanolysis. A limit of detection of 0.04 mg kg(-1), a limit of quantitation of 0.08 mg kg(-1), mean recoveries varying from 82% to 92%, and coefficients of variation ranging from 2.5% to 5.0% for repeatability and from 3.6% to 6.5% for within-laboratory reproducibility were obtained during in-house validation. The levels of the compounds in the evaluated samples, expressed as free 3-MCPD equivalent, ranged from not detected to 0.99 mg kg( )(1), and the highest concentrations were observed in samples of chopped onion and garlic. A preliminary estimation of 3-MCPD intake using these occurrence data suggested low risks to human health, but a potential concern may arise in particular cases of consumers of fried food. PMID- 26161903 TI - Site-Specific Dual Antibody Conjugation via Engineered Cysteine and Selenocysteine Residues. AB - Site-specific conjugation technologies enable the production of homogeneous antibody-drug conjugates (ADCs) with improved therapeutic indices compared to conventional ADCs. However, current site-specific conjugation methods can only attach one type of drug to a single antibody. Given the emergence of acquired resistance to current ADCs, arming single antibodies with different drugs may provide an attractive option in the development of next-generation ADCs. Here, we describe a site-specific dual conjugation strategy as a platform for dual warhead ADCs. PMID- 26161904 TI - Erratum: Phosphorene nanoribbon as a promising candidate for thermoelectric applications. PMID- 26161906 TI - Metal Iodate-Based Energetic Composites and Their Combustion and Biocidal Performance. AB - The biological agents that can be weaponized, such as Bacillus anthracis, pose a considerable potential public threat. Bacterial spores, in particular, are highly stress resistant and cannot be completely neutralized by common bactericides. This paper reports on synthesis of metal iodate-based aluminized electrospray assembled nanocomposites which neutralize spores through a combined thermal and chemical mechanism. Here metal iodates (Bi(IO3)3, Cu(IO3)2, and Fe(IO3)3) act as a strong oxidizer to nanoaluminum to yield a very exothermic and violent reaction, and simultaneously generate iodine as a long-lived bactericide. These microparticle-assembled nanocomposites when characterized in terms of reaction times and temporal pressure release show significantly improved reactivity. Furthermore, sporicidal performance superior to conventional metal-oxide-based thermites clearly shows the advantages of combining both a thermal and biocidal mechanism in spore neutralization. PMID- 26161905 TI - Non-Lethal Ionizing Radiation Promotes Aging-Like Phenotypic Changes of Human Hematopoietic Stem and Progenitor Cells in Humanized Mice. AB - Precise understanding of radiation effects is critical to develop new modalities for the prevention and treatment of radiation-induced damage. We previously reported that non-lethal doses of X-ray irradiation induce DNA damage in human hematopoietic stem and progenitor cells (HSPCs) reconstituted in NOD/Shi-scid IL2rgammanull (NOG) immunodeficient mice and severely compromise their repopulating capacity. In this study, we analyzed in detail the functional changes in human HSPCs in NOG mice following non-lethal radiation. We transplanted cord blood CD34+ HSPCs into NOG mice. At 12 weeks post transplantation, the recipients were irradiated with 0, 0.5, or 1.0 Gy. At 2 weeks post-irradiation, human CD34+ HSPCs recovered from the primary recipient mice were transplanted into secondary recipients. CD34+ HSPCs from irradiated mice showed severely impaired reconstitution capacity in the secondary recipient mice. Of interest, non-lethal radiation compromised contribution of HSPCs to the peripheral blood cells, particularly to CD19+ B lymphocytes, which resulted in myeloid-biased repopulation. Co-culture of limiting numbers of CD34+ HSPCs with stromal cells revealed that the frequency of B cell-producing CD34+ HSPCs at 2 weeks post-irradiation was reduced more than 10-fold. Furthermore, the key B-cell regulator genes such as IL-7R and EBF1 were downregulated in HSPCs upon 0.5 Gy irradiation. Given that compromised repopulating capacity and myeloid-biased differentiation are representative phenotypes of aged HSCs, our findings indicate that non-lethal ionizing radiation is one of the critical external stresses that promote aging of human HSPCs in the bone marrow niche. PMID- 26161908 TI - Formaldehyde exposure alters miRNA expression profiles in the olfactory bulb. AB - It has been reported that inhaling formaldehyde (FA) causes damage to the central nervous system. However, it is unclear whether FA can disturb the function of the olfactory bulb. Using a microarray, we found that FA inhalation altered the miRNA expression profile. Functional enrichment analysis of the predicted targets of the changed miRNA showed that the enrichment canonical pathways and networks associated with cancer and transcriptional regulation. FA exposure disrupts miRNA expression profiles within the olfactory bulb. PMID- 26161907 TI - Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome. AB - INTRODUCTION AND RESULTS: Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues. CONCLUSIONS: In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers with the aim to facilitate the identification of ICF patients. PMID- 26161909 TI - Water Use Patterns of Sympatric Przewalski's Horse and Khulan: Interspecific Comparison Reveals Niche Differences. AB - Acquiring water is essential for all animals, but doing so is most challenging for desert-living animals. Recently Przewalski's horse has been reintroduced to the desert area in China where the last wild surviving member of the species was seen before it vanished from China in the 1960s. Its reintroduction placed it within the range of a close evolutionary relative, the con-generic Khulan. Determining whether or not these two species experience competition and whether or not such competition was responsible for the extinction of Przewalski's horses in the wild over 50 years ago, requires identifying the fundamental and realized niches of both species. We remotely monitored the presence of both species at a variety of water points during the dry season in Kalamaili Nature Reserve, Xinjiang, China. Przewalski's horses drank twice per day mostly during daylight hours at low salinity water sources while Khulans drank mostly at night usually at high salinity water points or those far from human residences. Spatial and temporal differences in water use enables coexistence, but suggest that Przewalski's horses also restrict the actions of Khulan. Such differences in both the fundamental and realized niches were associated with differences in physiological tolerances for saline water and human activity as well as differences in aggression and dominance. PMID- 26161911 TI - Compressible elastomeric aerogels of hexagonal boron nitride and single-walled carbon nanotubes. AB - Lightweight porous ceramic materials that can recover their shapes after mechanical deformation have numerous applications. However, these types of materials tend to be highly fragile and often crack when compressed. Here, we report on the fabrication and characterization of highly porous, freestanding composites of hexagonal boron nitride (h-BN) and single-walled carbon nanotubes (SWCNTs) of density 13-15 mg mL(-1), which corresponds to a volume fraction of 0.009, that were mechanically robust and recovered their original shape even after uniaxially compressing them by more than 50%. We made these porous elastomeric composites using a solution based assembly process that involved first shaping SWCNTs into porous networks of density ~7 mg mL(-1) (volume fraction ~0.005) followed by coatings of SWCNT networks with 6-8 mg mL(-1) of h BN (volume fraction ~0.003-0.004). The h-BN coating strengthened the underlying SWCNT networks, likely via reinforcement of the nodes between the SWCNTs, resulting in an increase in Young's modulus by ~100% compared to that of SWCNT networks alone. Surprisingly, SWCNT networks, which were initially highly fragile, became elastomeric after h-BN coating, even though porous structures solely from h-BN are very brittle. Our fabrication approach preserves the morphology of the underlying networks, allowing for fabrication of various shapes and sizes of porous composites of h-BN and SWCNTs. Finally, our fabrication scheme is robust and facile for the preparation of porous composites of diverse ceramic materials and SWCNTs using the appropriate ceramic-precursor. PMID- 26161910 TI - Variability of Gross Tumor Volume in Nasopharyngeal Carcinoma Using 11C-Choline and 18F-FDG PET/CT. AB - This study was conducted to evaluate the variability of gross tumor volume (GTV) using 11C-Choline and 18F-FDG PET/CT images for nasopharyngeal carcinomas boundary definition. Assessment consisted of inter-observer and inter-modality variation analysis. Four radiation oncologists were invited to manually contour GTV by using PET/CT fusion obtained from a cohort of 12 patients with nasopharyngeal carcinoma (NPC) and who underwent both 11C-Choline and 18F-FDG scans. Student's paired-sample t-test was performed for analyzing inter-observer and inter-modality variability. Semi-automatic segmentation methods, including thresholding and region growing, were also validated against the manual contouring of the two types of PET images. We observed no significant variation in the results obtained by different oncologists in terms of the same type of PET/CT volumes. Choline fusion volumes were significantly larger than the FDG volumes (p < 0.0001, mean +/- SD = 18.21 +/- 8.19). While significantly consistent results were obtained between the oncologists and the standard references in Choline volumes compared with those in FDG volumes (p = 0.0025). Simple semi-automatic delineation methods indicated that 11C-Choline PET images could provide better results than FDG volumes (p = 0.076, CI = [-0.29, 0.025]). 11C-Choline PET/CT may be more advantageous in GTV delineation for the radiotherapy of NPC than 18F-FDG. Phantom simulations and clinical trials should be conducted to prove the possible improvement of the treatment outcome. PMID- 26161912 TI - Mercury Emission Ratios from Coal-Fired Power Plants in the Southeastern United States during NOMADSS. AB - We use measurements made onboard the National Science Foundation's C-130 research aircraft during the 2013 Nitrogen, Oxidants, Mercury, and Aerosol Distributions, Sources, and Sinks (NOMADSS) experiment to examine total Hg (THg) emission ratios (EmRs) for six coal-fired power plants (CFPPs) in the southeastern U.S. We compare observed enhancement ratios (ERs) with EmRs calculated using Hg emissions data from two inventories: the National Emissions Inventory (NEI) and the Toxics Release Inventory (TRI). For four CFPPs, our measured ERs are strongly correlated with EmRs based on the 2011 NEI (r(2) = 0.97), although the inventory data exhibit a -39% low bias. Our measurements agree best (to within +/-32%) with the NEI Hg data when the latter were derived from on-site emissions measurements. Conversely, the NEI underestimates by approximately 1 order of magnitude the ERs we measured for one previously untested CFPP. Measured ERs are uncorrelated with values based on the 2013 TRI, which also tends to be biased low. Our results suggest that the Hg inventories can be improved by targeting CFPPs for which the NEI- and TRI-based EmRs have significant disagreements. We recommend that future versions of the Hg inventories should provide greater traceability and uncertainty estimates. PMID- 26161913 TI - NaGdF4:Yb(3+)/Er(3+)@NaGdF4:Nd(3+)@Sodium-Gluconate: Multifunctional and Biocompatible Ultrasmall Core-Shell Nanohybrids for UCL/MR/CT Multimodal Imaging. AB - Multimodal bioimaging nanoparticles by integrating diverse imaging ingredients into one system, represent a class of emerging advanced materials that provide more comprehensive and accurate clinical diagnostics than conventional contrast agents. Here monodisperse and biocompatible core-shell nanoparticles, NaGdF4: Yb(3+)/Er(3+)@NaGdF4:Nd@sodium-gluconate (termed as GNa-Er@Nd), with about 26 nm in diameter were successfully prepared by a facile two step reactions in high boiling solvents, and followed a ligand exchange process with sodium gluconate. The resulting GNa-Er@Nd nanoparticles were well characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectra (FTIR), and zeta potentials. These nanohybrids present brightly dual wavelength excited upconversion luminescence (UCL) under both 980 and 793 nm laser because of the synergistic effect of Yb(3+)/Er(3+) and Nd(3+). They also exhibited excellent relaxivity parameters (r1) in magnetic resonance imaging (MRI) and Hounsfield units (HU) in X-ray computed tomography (CT) that are comparable to the clinical contrast agents. Therefore, these small and monodisperse nanoparticles provide options to construct a unique platform for potential multimodal UCL/CT/MRI imaging simultaneously. PMID- 26161914 TI - Cerebral Vasoactivity and Oxygenation with Oxygen Carrier M101 in Rats. AB - The severity of traumatic brain injury (TBI) may be reduced if oxygen can be rapidly provided to the injured brain. This study evaluated if the oxygen-carrier M101 causes vasoconstricton of pial vasculature in healthy rats (Experiment 1) and if M101 improves brain tissue oxygen (PbtO2) in rats with controlled cortical impact (CCI)-TBI (Experiment 2). M101 (12.5 mL/kg intravenous [IV] over 2 h) caused a mild (9 mm Hg) increase in the mean arterial blood pressure (MAP) of healthy rats without constriction of cerebral pial arterioles. M101 (12 mL/kg IV over 1 h) caused a modest (27 mm Hg) increase in MAP (peak, 123 +/- 5 mm Hg [mean +/- standard error of the mean]) of CCI-TBI rats and restored PbtO2 to near pre injury levels. In both M101 and untreated control (NON) groups, PbtO2 was ~30 +/- 2 mm Hg pre-injury and decreased (p <= 0.05) to ~16 +/- 2 mm Hg 15 min after CCI. In NON, PbtO2 remained ~50% of baseline but M101 administration resulted in a sustained increase in PbtO2 (peak, 25 +/- 5 mm Hg), which was not significantly different from pre-injury until the end of the study, when it decreased again below pre-injury (but was still higher than NON). Histopathology showed no differences between groups. In conclusion, M101 increased systemic blood pressures without concurrent cerebral pial vasoconstriction (in healthy rats) and restored PbtO2 to 86% of pre-injury for at least 80 min when given soon after CCI TBI. M101 should be evaluated in a clinically-relevant large animal model for pre hospital treatment of TBI. PMID- 26161915 TI - Management of Corneal Bee Sting Injuries. AB - PURPOSE: To review the management of keratitis after corneal bee stings and to report a case of deep stromal corneal infiltrate secondary to a retained bee stinger managed conservatively in a patient who presented three days after unsanitary manipulation of the stinger apparatus. METHODS: Case report and review of literature. RESULTS: A 57-year-old male beekeeper was evaluated for pain, blurry vision, and photosensitivity after a corneal bee sting. Of note, the venom sac had been removed with dirty tweezers three days prior to his visit. On exam, a focal infiltrate with diffuse edema was seen surrounding a retained bee stinger in the peripheral cornea. Trace cells in the anterior chamber were also noted. Based on a high suspicion for infectious keratitis, a conservative treatment strategy was elected. Administration of broad-spectrum topical antibiotics with concomitant abstention of corticosteroids led to rapid resolution of the symptoms. Over 16 months of follow-up, the stinger has remained in situ without migration and the patient has maintained 20/20 visual acuity without complications. There is debate on the preferred method for the management of corneal injury secondary to bee stings, especially when it is associated with a retained stinger. We herein present our findings in our appraisal of reported cases. CONCLUSION: In the aftermath of an ocular bee sting, close surveillance for inflammation and infection is essential. Individual manifestations of these injuries vary in timing, type, and severity; therefore, the accessibility of the stinger and the evolving clinical picture should guide therapeutic decisions. PMID- 26161920 TI - Applying knowledge of autism to brain cancer management: what do we know? PMID- 26161922 TI - Does genetic susceptibility increase risk for neurocognitive decline among patients with acute lymphoblastic leukemia? PMID- 26161921 TI - Circulating tumor cells as biomarkers of head and neck squamous cell carcinoma: an updated view. PMID- 26161923 TI - Inside the 2015 ASCO Genitourinary Cancers Symposium. AB - The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, Rosen Shingle Creek, Orlando, FL, USA, 26-28 February 2015 The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium was held in Orlando (FL, USA), from 26 to 28 February 2015. This meeting was focused on 'Integrating Biology into patient-centric care' and represented an attractive opportunity for oncology professionals with a special interest in the diagnosis and treatment of genitourinary tumors. The identification and validation of biomarkers for tumor response had been the focus of several researchers at the symposium, together with the development of novel targeted agents. This report is a summary of the highlights on kidney and prostate tumors presented at the 2015 ASCO Genitourinary Cancers Symposium by various investigators. PMID- 26161924 TI - Sorafenib: 10 years after the first pivotal trial. AB - Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings. We also discuss the perspectives on the use of this molecule, including the role of sorafenib as comparator for the development of new drugs, the combination of sorafenib with additional therapies (such as transarterial chemoembolization for hepatocellular carcinoma) and the use of this treatment in several other advanced refractory solid tumors. PMID- 26161925 TI - Denosumab for the treatment of giant cell tumor of the bone. AB - Giant cell tumor of bone is typically composed of neoplastic stromal cells and non-neoplastic osteoclastic giant cells. RANK-expressing osteoclastic giant cells are recruited by RANK ligand excreted by the stromal cells, and used by these neoplastic cells to create expansion space. Denosumab specifically binds to and inhibits RANK ligand, thereby eradicating osteoclastic giant cells from the tumor and thus reducing osteolytic activity. Clinical studies reported disease stabilization and clinical benefit in terms of reduced pain and analgesics use, avoided surgeries or surgeries with less morbid procedures. Adverse events observed in patients with giant cell tumor of bone were consistent with the known safety profile of denosumab with a very low incidence of hypocalcemia and osteonecrosis. Overall, denosumab was shown to suppress osteolytic activity and slow disease progression and is thus a treatment option for patients with giant cell tumor of bone. PMID- 26161926 TI - The CLL12 trial protocol: a placebo-controlled double-blind Phase III study of ibrutinib in the treatment of early-stage chronic lymphocytic leukemia patients with risk of early disease progression. AB - Observation (watch and wait) is the standard of care for patients with asymptomatic Binet stage A chronic lymphocytic leukemia (CLL). However, the clinical course of these patients is very heterogeneous with some patients requiring treatment rather soon and others not progressing for ages. The clinical staging does not reflect this high variability of the clinical course of CLL. Published data demonstrate that the comprehensive use of several risk factors dramatically improves the accuracy of prognostication independent of clinical stage. The treatment of CLL underwent considerable changes with the introduction of kinase-inhibitors, including ibrutinib, an orally administered, well-tolerated and potent inhibitor of Bruton's tyrosine kinase. This is the first prospective, multicenter, placebo-controlled, double-blind, Phase III study to compare efficacy and safety of ibrutinib to a watch-and-wait approach in Binet stage A CLL with risk of disease progression defined by the comprehensive CLL score. PMID- 26161927 TI - KRAS mutation status is associated with specific pattern of genes expression in pancreatic adenocarcinoma. AB - AIMS: To evaluate potential differences at a molecular level between KRAS mutant tumors (MT) and KRAS wild-type (WT) pancreatic tumors and the biological and prognostic significance of different KRAS mutations. MATERIALS & METHODS: Expression of a panel of 29 genes was analyzed in KRAS WT and MT tumors. Effects of KRAS mutation and gene expression levels were assessed on patients' survival. RESULTS: MUC6 (p = 0.009), HGF (p = 0.011), VEGFR-2 (p = 0.020) and VEGFB (p = 0.026) were significantly more expressed and SMAD4 was less suppressed (p = 0.003) in WT KRAS. Contrariwise, SHH (p = 0.012) and IHH (p = 0.031) were more expressed in MT KRAS patients. No OS difference was found between WT and MT KRAS tumors. CONCLUSION: KRAS mutation status seems to identify two different subtypes of pancreatic ductal adenocarcinoma with similar outcome but distinct molecular features and probably different therapeutic targets. PMID- 26161928 TI - KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer. AB - AIM: To investigate the impact of KRAS mutation variants on the activity of regorafenib in SW48 colorectal cancer cells. MATERIALS & METHODS: Activity of regorafenib was evaluated in isogenic SW48 KRAS wild-type (WT) and mutant cells. Subcutaneous xenografts (KRAS WT and G12C mutant variants) in NOD/SCID mice were analyzed to elucidate the effect of regorafenib treatment in vivo. RESULTS: Compared with KRAS WT cells, all mutant variants seemed associated with some degree of resistance to regorafenib-treatment in vitro. In vivo, activation of apoptosis (TUNEL) and reduction of proliferation (Ki67) after treatment with regorafenib were more pronounced in KRAS WT tumors as compared with G12C variants. CONCLUSION: In SW48 cells, exon 2 mutations of the KRAS gene may influence antitumor effects of regorafenib. PMID- 26161929 TI - Evolution in the treatment of gastroenteropancreatic-neuroendocrine neoplasms, focus on systemic therapeutic options: a systematic review. AB - Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors. The present review discusses current therapeutic strategies for the treatment of gastro entero-pancreatic NEN. Several systemic options are currently available, including medical systemic chemotherapy, biological drugs, somatostatin analogs and peptide receptor radionuclide therapy. The carcinoid syndrome can be adequately controlled with somatostatin analogs; chemotherapy has shown positive outcomes in poor prognosis patients, and peptide receptor radionuclide therapy is a promising treatment based on the use of radioisotopes for advanced disease expressing somatostatin receptors. Targeted therapies, such as multikinase inhibitors and monoclonal antibodies are also recommended or under evaluation for the treatment of advanced NENs, but some critical issues in clinical practice remain unresolved. Depending upon the development of the disease, a multimodal approach is recommended. The treatment strategy for metastatic patients should be planned by a multidisciplinary team in order to define the optimal sequence of treatments. PMID- 26161930 TI - Nanotechnology in the war against cancer: new arms against an old enemy - a clinical view. AB - Clinical oncology is facing a paradigm shift. A new treatment philosophy is emerging and new targets are appearing that require new active agents. The medical use of nanotechnology - nanomedicine - holds several promising possibilities in the war against cancer. Some of these include: new formats for old drugs, that is, increasing efficacy while diminishing side effects; and new administration routes - that is, dermal, oral and pulmonary. In this overview, we describe some nanoparticles and their medical uses as well as highlight advantages of nanoparticles compared with conventional pharmaceuticals. We also point to some of the many technical challenges and potential risks with using nanotechnology for oncological applications. PMID- 26161932 TI - Associations between physical function, dual-task performance and cognition in patients with mild Alzheimer's disease. AB - OBJECTIVE: Alzheimer's disease (AD) causes a gradual decline in cognition, limitations of dual-tasking and physical function leading to total dependence. Hence, information about the interaction between physical function, dual-task performance and cognition may lead to new treatment strategies with the purpose of preserving function and quality of life. The objective of this study was to investigate the associations between physical function, dual-task performance and cognition in community-dwelling patients with mild AD. METHODS: Baseline results from 185 participants (50-90 years old) in the single blinded multicenter RCT 'ADEX' (Alzheimer's disease: the effect of physical exercise) were used. Assessments included tests of physical function: 400-m walk test, 10-m walk test, Timed Up and Go test and 30-s chair stand test; dual-task performance, i.e., 10-m walk while counting backwards from 50 or naming the months backwards; and cognition, i.e., Mini Mental State Examination, Symbol Digit Modalities Test, the Stroop Color and Word Test, and Lexical verbal fluency test. RESULTS: Results in the 30-s chair stand test correlated significantly with all tests of cognition (r = .208-.242) while the other physical function tests only randomly correlated with tests of cognition. Results in the dual-task counting backwards correlated significantly with results in all tests of cognition (r = .259-.388), which accounted for 7%-15% of the variation indicating that a faster time to complete dual-task performance was associated with better cognitive performance. CONCLUSION: The evidence of the associations between physical function, dual-task performance and cognition is important when creating new rehabilitation interventions to patients with mild AD. PMID- 26161933 TI - Ultrafast Vibrational Echo Spectroscopy of Liquid Water from First-Principles Simulations. AB - Vibrational echo spectroscopy has become a powerful technique to study vibrational spectral diffusion in water and aqueous solutions. The dynamics of vibrational spectral diffusion is intimately related to the hydrogen bond fluctuations in liquid water and other hydrogen bonded liquids. Earlier theoretical calculations of vibrational echo spectroscopy of aqueous systems were based on classical molecular dynamics simulations involving empirical force fields of water. In the current work, we have employed the method of ab initio molecular dynamics simulation to calculate the spectral observables of vibrational echo and two-dimensional infrared (2D-IR) spectroscopy of liquid water at room temperature under Condon and cumulant approximations. The time scales extracted from the temporal decay of the frequency-time correlation function (FTCF), short-time slope of three pulse photon echo (SP3E), dynamic line width (DLW), and the slope of nodal line of 2D-IR spectra are found to be in reasonably close agreement with each other which reinforces the assertion that signatures of FTCF can be captured using three pulse photon echo and 2D-IR spectroscopy. PMID- 26161931 TI - Next-generation surveillance strategies for patients with lymphoma. AB - While remission and cure rates for Hodgkin and non-Hodgkin lymphoma continue to improve, surveillance approaches remain controversial, especially in light of recent reports suggesting limited benefit for routine radiologic assessment. Routine cross-sectional imaging results in considerable patient expense and anxiety, and this approach does not clearly improve patient outcomes. Next generation approaches including minimal residual disease detection may provide an opportunity to identify relapse early and intervene prior to progression of clinical disease. This review discusses the role of surveillance imaging in Hodgkin and non-Hodgkin lymphoma and provides an introduction to serologic assessment of minimal residual disease. Future studies will need to focus on the clinical application of minimal residual disease surveillance and its ability to predict relapse, treatment response and survival. PMID- 26161934 TI - Aminopyridine derivatives controlled the assembly and various properties of Cu BTC metal-organic frameworks. AB - Three Cu(ii) metal-organic frameworks (MOFs) based on 1,3,5-benzenetricarboxylic acid (H3BTC) and three aminopyridine derivatives with different lengths and coordination groups, namely [Cu2(3-azpy)(HBTC)(H2BTC)(MU3-OH)(H2O)2] (), [Cu2(3 ppca)(BTC)(H2O)3].H2O (), [Cu2(3-ebpba)(BTC)(MU3-OH)] () [3-azpy = 3,3' azopyridine, 3-ppca = N-(pyridin-3-yl)pyrazine-2-carboxamide, 3-ebpba = (E)-4,4' (ethene-1,2-diyl)bis(N-pyridin-3-yl)benzamide)], have been hydrothermally synthesized and structurally characterized by elemental analyses, IR, PXRD, TG and single crystal X-ray diffraction analyses. The title MOFs display versatile structural features with 2D and 3D frameworks. Complex exhibits a 2D layer, which is constructed from the 3-azpy bridging ligands and a 1D ladder-like Cu-BTC chain with tetranuclear copper clusters. The 3-azpy was in situ transformed from 3 aminopyridine under the hydrothermal conditions. Complex shows a rare 3D framework, which features a (3,3,3,3)-connected topology with a Schlafli symbol of {8.10.12}2{8(2).10}2. Complex exhibits a (3,8)-connected {4.6(2)}2{4(2).6(22).7.8(3)} topology based on tetranuclear copper clusters. The influence of aminopyridine-based ligands on the structures and properties of the title complexes has been discussed. The electrocatalytic and photocatalytic properties of complexes have also been investigated in detail. PMID- 26161937 TI - A pre-formulation study of a polymeric solid dispersion of paclitaxel prepared using a quasi-emulsion solvent diffusion method to improve the oral bioavailability in rats. AB - OBJECTIVE: To preliminarily develop a surfactant-free, polymeric solid dispersion (PSD) of paclitaxel suitable for oral administration. METHODS: A co-solvent quench method was applied to screen the proper polymer matrix of the PSD which were prepared in a liquid system using a quasi-emulsion solvent diffusion method (QESDM). Three dissolution experiments and two in vivo tests in rats were used to explain the differences among the formulations. RESULTS: The theoretical solubility ratio of amorphous/crystalline PTX was 92.6 (37 degrees C). Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was chosen as the polymer carrier of the PSD and a porous silicon dioxide [called white carbon black (WCB)] was selectable to be used to further adjust the dissolution rate. The absolute oral bioavailability (AOB, 20 mg/kg) of the three formulas [HPMCAS/paclitaxel/WCB = 4/1/0 (F1), 8/1/0 (F2) and 4/1/4 (F3), w/w/w] were 11.8, 13.6 and 25.6%, respectively. The AOB of F3 is nearly seven times higher than that (3.8%) of paclitaxel material (a control). The advantage of higher HPMCAS/paclitaxel ratio of F2 in a dissolution test was not reflected in the first in vivo test due to the relatively higher dose of polymer which could not be effectively dissolved under the limitation of intestinal environment. This was deduced from the dissolution tests and was finally validated when the oral dose of PTX (and thus polymer) was reduced. The relevant AOBs (10 mg/kg) were 10.4, 20.8 and 19.6%, respectively. CONCLUSION: The PSD is a promising formulation strategy and the QESDM is a practical preparation method to implement such formulation design. PMID- 26161938 TI - Penetration enhancing effects of selected natural oils utilized in topical dosage forms. AB - CONTEXT: Various natural products, including oils, have been utilized as penetration enhancers due to their "safety profiles". These oils contain fatty acids promoting skin permeability through lipid fluidization within the stratum corneum; and might therefore be able to effectively enhance transdermal drug delivery. OBJECTIVE: We investigated possible penetration enhancing properties of selected oils, utilizing flurbiprofen as marker compound in emulgel formulations. The formulations were compared to a liquid paraffin emulgel and a hydrogel to establish any significant penetration enhancing effects. METHODS: Gas chromatographic analysis of the natural oils was performed at ambient temperature to determine the fatty acid composition in each selected natural oils. Franz cell diffusion studies and tape stripping methods were employed to study delivery of the marker into, and through the skin. RESULTS: The following rank order for the emulgel flux-values was obtained: Hydrogel >>>> olive oil >> liquid paraffin >> coconut oil > grape seed oil >> Avocado oil >= Crocodile oil >> Emu oil. DISCUSSION: Results suggested that oils containing predominantly mono-unsaturated oleic acid, on average increased the flux of the marker to a larger extent than oils containing an almost even mixture of both mono- and poly-unsaturated fatty acids. Oils comprising saturated fatty acids (SFAs) with alkyl chains between C12 and C14, increased the marker flux to a higher extent than oils containing C16 C18 SFAs. Effects observed for branched fatty acids, however, did not vary significantly from effects for unbranched fatty acids with the same carbon chain length. CONCLUSION: Natural oils possess penetration enhancing effects. PMID- 26161936 TI - Geometry of the Gene Expression Space of Individual Cells. AB - There is a revolution in the ability to analyze gene expression of single cells in a tissue. To understand this data we must comprehend how cells are distributed in a high-dimensional gene expression space. One open question is whether cell types form discrete clusters or whether gene expression forms a continuum of states. If such a continuum exists, what is its geometry? Recent theory on evolutionary trade-offs suggests that cells that need to perform multiple tasks are arranged in a polygon or polyhedron (line, triangle, tetrahedron and so on, generally called polytopes) in gene expression space, whose vertices are the expression profiles optimal for each task. Here, we analyze single-cell data from human and mouse tissues profiled using a variety of single-cell technologies. We fit the data to shapes with different numbers of vertices, compute their statistical significance, and infer their tasks. We find cases in which single cells fill out a continuum of expression states within a polyhedron. This occurs in intestinal progenitor cells, which fill out a tetrahedron in gene expression space. The four vertices of this tetrahedron are each enriched with genes for a specific task related to stemness and early differentiation. A polyhedral continuum of states is also found in spleen dendritic cells, known to perform multiple immune tasks: cells fill out a tetrahedron whose vertices correspond to key tasks related to maturation, pathogen sensing and communication with lymphocytes. A mixture of continuum-like distributions and discrete clusters is found in other cell types, including bone marrow and differentiated intestinal crypt cells. This approach can be used to understand the geometry and biological tasks of a wide range of single-cell datasets. The present results suggest that the concept of cell type may be expanded. In addition to discreet clusters in gene-expression space, we suggest a new possibility: a continuum of states within a polyhedron, in which the vertices represent specialists at key tasks. PMID- 26161939 TI - Application of NIR chemometric methods for quantification of the crystalline fraction of warfarin sodium in drug product. AB - Monitoring of the physical state of warfarin sodium (WS) in products is essential for minimizing product quality variability in order to ensure consistent clinical performance. This study reports the development of chemometric models for quantifying the crystalline and amorphous fractions of WS in commercial drug products using NIR spectroscopy. Formulations based on commercially available products with different API to excipient ratio were used for the study. For each content, two formulations containing either lactose monohydrate or lactose anhydrous as the predominant formulation excipient were prepared. Two formulations containing either 100% amorphous WS (AWS) or crystalline WS (CWS) were prepared and mixed in various ratios to obtain sample matrices containing AWS/CWS 0-100%. The uniformity of the samples was confirmed by near infrared chemical imaging. Data were mathematically pretreated by multiplicative signal correction and Savitzky-Golay second derivative. Principal component regression and partial least square regression models were developed from mathematically treated data. All the models showed linear trend for amorphous and crystalline fractions of the WS as indicated by correlation and R(2) > 0.99 and >0.98, respectively. The models demonstrated good performance parameters with a low-root mean squared error, standard error and bias. The model predicted CWS and AWS contents were in very close agreement with the actual values. The study indicated the utility of NIR chemometric methods in quantification of the crystalline and/or amorphous fraction of WS in its products. PMID- 26161940 TI - Co-processing as a tool to improve aqueous dispersibility of cellulose ethers. AB - Cellulose ethers are important materials with numerous applications in pharmaceutical industry. They are widely employed as stabilizers and viscosity enhancers for dispersed systems, binders in granulation process and as film formers for tablets. These polymers, however, exhibit challenge during preparation of their aqueous dispersions. Rapid hydration of their surfaces causes formation of a gel that prevents water from reaching the inner core of the particle. Moreover, the surfaces of these particles become sticky, thus leading to agglomeration, eventually reducing their dispersion kinetics. Numerous procedures have been tested to improve dispersibility of cellulose ethers. These include the use of cross-linking agents, alteration in the synthesis process, adjustment of water content of cellulose ether, modification by attaching hydrophobic substituents and co-processing using various excipients. Among these, co-processing has provided the most encouraging results. This review focuses on the molecular mechanisms responsible for the poor dispersibility of cellulose ethers and the role of co-processing technologies in overcoming the challenge. An attempt has been made to highlight various co-processing techniques and specific role of excipients used for co-processing. PMID- 26161943 TI - Influence of Dietary Selenium Species on Selenoamino Acid Levels in Rainbow Trout. AB - Two forms of selenium (Se) supplementation of fish feeds were compared in two different basal diets. A 12-week feeding trial was performed with rainbow trout fry using either a plant-based or a fish meal-based diet. Se yeast and selenite were used for Se supplementation. Total Se and Se speciation were determined in both diets and whole body of trout fry using inductively coupled plasma mass spectrometry (ICP MS) and high-performance liquid chromatography (HPLC). The two selenoamino acids, selenomethionine (SeMet) and selenocysteine (SeCys), were determined in whole body of fry after enzymatic digestion using protease type XIV with a prior derivatization step in the case of SeCys. The plant-based basal diet was found to have a much lower total Se than the fish meal-based basal diet with concentrations of 496 and 1222 MUg(Se) kg(-1), respectively. Dietary Se yeast had a higher ability to raise whole body Se compared to selenite. SeMet concentration in the fry was increased only in the case of Se yeast supplementation, whereas SeCys levels were similar at the end of the feeding trial for both Se supplemented forms. The results show that the fate of dietary Se in fry is highly dependent on the form brought through supplementation and that a plant-based diet clearly benefits from Se supplementation. PMID- 26161944 TI - Distortion of Ultrathin Photocleavable Block Copolymer Films during Photocleavage and Nanopore Formation. AB - Highly ordered block copolymer thin films have been studied extensively during the last years because they afford versatile self-assembled morphologies via a bottom-up approach. They promise to be used in applications such as polymeric membranes or templates for nanostructured materials. Among the block copolymer structures, perpendicular cylinders have received strong attention due to their ability to fabricate highly ordered nanopores and nanowires. Nanopores can be created from a thin block copolymer film upon the removal of one block by selective etching or by dissolution of one polymer block. Here we demonstrate the utilization of polystyrene-block-poly(ethylene oxide) diblock copolymer (PS-hnu PEO) with an ortho-nitrobenzyl ester (ONB) as the photocleavable block-linker to create highly ordered thin films. Removal of the PEO block by choosing an appropriate solvent upon photocleavage is expected to yield arrays of nanopores decorated with functional groups, thus lending itself to adsorption or filtration uses. While the feasibility of this approach has been demonstrated, it is crucial to understand the influence of removal conditions (i.e., efficiency of photocleavage as well as best washing solvent) and to evaluate changes in the surface topology and inner structure upon photocleavage. To this end, the time dependence evolution of the surface morphology of block copolymer thin films was studied using grazing-incidence small-angle X-ray scattering (GISAXS) technique in combination with scanning probe microscopy. PMID- 26161942 TI - Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal Cholesterol Absorption in C57BL/6J Mice. AB - We previously demonstrated that Nostoc commune var. sphaeroids Kutzing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in cholesterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal cholesterol absorption, and fecal sterol excretion. Plasma total cholesterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of sterol regulatory element binding protein 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), carnitine palmitoyltransferase-1alpha, and acyl-CoA oxidase 1 were induced in 5% NO-fed mice, while there were no significant changes in hepatic lipogenic gene expression between groups. NO, but not NOE and SP groups, significantly decreased intestinal cholesterol absorption. When HepG2 cells and primary mouse hepatocytes were incubated with NOE and SP organic extract (SPE), there were marked decreases in protein levels of HMGR, low-density lipoprotein receptor, and fatty acid synthase. In conclusion, the nonlipid fraction of NO exerts TC and TG-lowering effects primarily by inhibiting intestinal cholesterol absorption and by increasing hepatic fatty acid oxidation, respectively. PMID- 26161945 TI - Hospice Eligibility and Election: Does Policy Prepare Us to Meet the Need? AB - A 7-point policy model is used to examine policy on hospice eligibility and election in the United States. Despite the growth of hospice, many eligible patients continue to lack access due to difficulties experienced by providers in discerning 6-month prognoses among chronically ill patients, the inability of patients to elect hospice alongside curative care, and limited reimbursement for hospice providers. Though the landscape of dying has evolved, with more deaths occurring later in life from chronic illness, Medicare hospice eligibility requirements have historically remained the same. Utilization would increase if hospice agencies were able to provide fewer restrictions by including ongoing treatments such as transfusions, intravenous nutrition, or palliative radiation. Hospices would be more likely to enroll critically ill patients who require some ongoing curative measures if Medicare reimbursement rates were higher, and patients would be more likely to seek hospice earlier if Medicare election policies were altered to allow concurrent care. Participation would also be increased by extending hospice eligibility past the traditional prognosis of 6 months. Though expansion in public spending of hospice care has been met with some opposition, current research suggests that potential savings due to decreased costs in acute care is promising. PMID- 26161946 TI - Structural Evolution of Iron Antimonides from Amorphous Precursors to Crystalline Products Studied by Total Scattering Techniques. AB - Homogeneous reaction precursors may be used to form several solid-state compounds inaccessible by traditional synthetic routes, but there has been little development of techniques that allow for a priori prediction of what may crystallize in a given material system. Here, the local structures of FeSbx designed precursors are determined and compared with the structural motifs of their crystalline products. X-ray total scattering and atomic pair distribution function (PDF) analysis are used to show that precursors that first nucleate a metastable FeSb3 compound share similar local structure to the product. Interestingly, precursors that directly crystallize to thermodynamically stable FeSb2 products also contain local structural motifs of the metastable phase, despite their compositional disagreement. While both crystalline phases consist of distorted FeSb6 octahedra with Sb shared between either two or three octahedra as required for stoichiometry, a corner-sharing arrangement indicative of AX3 type structures is the only motif apparent in the PDF of either precursor. Prior speculation was that local composition controlled which compounds nucleate from amorphous intermediates, with different compositions favoring different local arrangements and hence different products. This data suggests that local environments in these amorphous intermediates may not be very sensitive to overall composition. This can provide insight into potential metastable phases which may form in a material system, even with a precursor that does not crystallize to the kinetically stabilized product. Determination of local structure in homogeneous amorphous reaction intermediates from techniques such as PDF can be a valuable asset in the development of systematic methods to prepare targeted solid-state compounds from designed precursors. PMID- 26161947 TI - Corrigendum: An evolutionary inspection game with labour unions on small-world networks. PMID- 26161948 TI - Application of the Exact Dispersion Solution to the Analysis of Solutes beyond the Limits of Taylor Dispersion. AB - Taylor dispersion analysis (TDA) is a fast and simple method for determining hydrodynamic radii. The method is applicable under conditions that allow the solute molecules to diffuse appreciably across the cross section of the flow before its measurement. This mitigates the effects of early stage convection on the dispersion and thus imposes a lower bound on the value of the diffusion coefficient measurable at a given flow speed. In this paper, we use the exact solution to the dispersion problem to analyze solutes outside the limits of TDA. Furthermore, by modeling the early stage convection, we analyze a mixture of two solutes with significantly different sizes that mimics heavily aggregated samples. The results obtained from the fits in both cases were in good agreement to the expected values. This demonstrates the potential of the model to extend dispersion analysis to regimes well outside the TDA limits such as the analysis of large molecules and the use of high flow-rates. PMID- 26161949 TI - Palladium-Catalyzed Oxalyl Amide Directed Silylation and Germanylation of Amine Derivatives. AB - Palladium-catalyzed direct ortho-silylation of oxalyl amide-protected phenylmethanamine and phenethylamine with commercially available disilanes is reported. Germanylation products were also produced under the same reaction conditions. This protocol tolerated oxalyl amide-protected aliphatic amines, which gave gamma-C-H silylation products. PMID- 26161950 TI - Prb1 Protease Activity Is Required for Its Recognition by the F-Box Protein Saf1. AB - The SCF ubiquitin ligase associates with substrates through its F-box protein adaptor. Substrates are typically recognized through a defined phosphodegron. Here, we characterize the interaction of the F-box protein Saf1 with Prb1, one of its vacuolar protease substrates. We show that Saf1 binds the mature protein but ubiquitinates only the zymogen precursor. The ubiquitinated lysine was found to be in a peptide eliminated from the mature protein. Mutations that eliminate the catalytic activity of Prb1, or the related substrate Prc1, block Saf1 targeting of the zymogen precursor. Our data suggest that Saf1 does not require a conventional degron as do other F-box proteins but instead recognizes the catalytic site itself. PMID- 26161951 TI - Room-Temperature Cu(II)-Catalyzed Chemo- and Regioselective Ortho-Nitration of Arenes via C-H Functionalization. AB - An efficient Cu-catalyzed chemo- and regioselective ortho-nitration of N,1-diaryl 5-aminotetrazoles and N,4-diaryl-3-amino-1,2,4-triazoles have been described with good functional group compatibility. The procedure features the use of operationally simple protocol utilizing the commercially available less toxic CuCl2.2H2O as catalyst and Fe(NO3)3.9H2O as nitration source at room temperature. Removal of the 5-aminotetrazole directing group has been demonstrated using base hydrolysis to afford substituted 2-nitroanilines. PMID- 26161953 TI - On Pixel-Wise Explanations for Non-Linear Classifier Decisions by Layer-Wise Relevance Propagation. AB - Understanding and interpreting classification decisions of automated image classification systems is of high value in many applications, as it allows to verify the reasoning of the system and provides additional information to the human expert. Although machine learning methods are solving very successfully a plethora of tasks, they have in most cases the disadvantage of acting as a black box, not providing any information about what made them arrive at a particular decision. This work proposes a general solution to the problem of understanding classification decisions by pixel-wise decomposition of nonlinear classifiers. We introduce a methodology that allows to visualize the contributions of single pixels to predictions for kernel-based classifiers over Bag of Words features and for multilayered neural networks. These pixel contributions can be visualized as heatmaps and are provided to a human expert who can intuitively not only verify the validity of the classification decision, but also focus further analysis on regions of potential interest. We evaluate our method for classifiers trained on PASCAL VOC 2009 images, synthetic image data containing geometric shapes, the MNIST handwritten digits data set and for the pre-trained ImageNet model available as part of the Caffe open source package. PMID- 26161952 TI - Characterization of Novel Src Family Kinase Inhibitors to Attenuate Microgliosis. AB - Microgliosis is a major hallmark of Alzheimer's disease (AD) brain pathology. Abeta peptide is hypothesized to act as a stimulus for microglia leading to activation of non-receptor tyrosine kinases and subsequent secretion of pro inflammatory cytokines. Therefore, the signaling pathways mediating microglial activation may be important therapeutic targets of anti-inflammatory therapy for AD. Four novel compounds were chosen after high throughput screening kinase activity assays determined them as potential Lyn kinase inhibitors. Their kinase inhibitory and anti-inflammatory effect on Abeta-stimulated activation was assessed using the murine microglial cell line, BV2. Cells were treated with the compounds to determine effects on active, phosphorylated levels of Src family kinases, Src and Lyn, as well as MAP kinases ERK, JNK and p38. Only one compound, LDDN-0003499, produced a dose dependent decrease in basal levels of active, phosphorylated Src and Lyn in the BV2 cells. LDDN-0003499 treatment also attenuated the Abeta-stimulated increase in active, phosphorylated levels of Lyn/Src and TNFalpha and IL-6 secretion. This study identifies a novel small molecule Src family tyrosine kinase inhibitor with anti-inflammatory effects in response to Abeta stimulation of microglia. Further in vitro/in vivo characterization of LDDN-0003499 as well as structural modification may provide a new tool for attenuating microglial-mediated brain inflammatory conditions such as that occurring in AD. PMID- 26161954 TI - Facial Features: What Women Perceive as Attractive and What Men Consider Attractive. AB - Attractiveness plays an important role in social exchange and in the ability to attract potential mates, especially for women. Several facial traits have been described as reliable indicators of attractiveness in women, but very few studies consider the influence of several measurements simultaneously. In addition, most studies consider just one of two assessments to directly measure attractiveness: either self-evaluation or men's ratings. We explored the relationship between these two estimators of attractiveness and a set of facial traits in a sample of 266 young Spanish women. These traits are: facial fluctuating asymmetry, facial averageness, facial sexual dimorphism, and facial maturity. We made use of the advantage of having recently developed methodologies that enabled us to measure these variables in real faces. We also controlled for three other widely used variables: age, body mass index and waist-to-hip ratio. The inclusion of many different variables allowed us to detect any possible interaction between the features described that could affect attractiveness perception. Our results show that facial fluctuating asymmetry is related both to self-perceived and male rated attractiveness. Other facial traits are related only to one direct attractiveness measurement: facial averageness and facial maturity only affect men's ratings. Unmodified faces are closer to natural stimuli than are manipulated photographs, and therefore our results support the importance of employing unmodified faces to analyse the factors affecting attractiveness. We also discuss the relatively low equivalence between self-perceived and male-rated attractiveness and how various anthropometric traits are relevant to them in different ways. Finally, we highlight the need to perform integrated-variable studies to fully understand female attractiveness. PMID- 26161956 TI - Competing for Attention in Social Media under Information Overload Conditions. AB - Modern social media are becoming overloaded with information because of the rapidly-expanding number of information feeds. We analyze the user-generated content in Sina Weibo, and find evidence that the spread of popular messages often follow a mechanism that differs from the spread of disease, in contrast to common belief. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that for certain messages the chance of an individual to share the message is proportional to the fraction of its neighbours who shared it with him/her, which is a result of competition for attention. We model this process using a fractional susceptible infected recovered (FSIR) model, where the infection probability of a node is proportional to its fraction of infected neighbors. Our findings have dramatic implications for information contagion. For example, using the FSIR model we find that real-world social networks have a finite epidemic threshold in contrast to the zero threshold in disease epidemic models. This means that when individuals are overloaded with excess information feeds, the information either reaches out the population if it is above the critical epidemic threshold, or it would never be well received. PMID- 26161955 TI - DAPIT Over-Expression Modulates Glucose Metabolism and Cell Behaviour in HEK293T Cells. AB - INTRODUCTION: Diabetes Associated Protein in Insulin-sensitive Tissues (DAPIT) is a subunit of mitochondrial ATP synthase and has also been found to associate with the vacuolar H+-ATPase. Its expression is particularly high in cells with elevated aerobic metabolism and in epithelial cells that actively transport nutrients and ions. Deletion of DAPIT is known to induce loss of mitochondrial ATP synthase but the effects of its over-expression are obscure. RESULTS: In order to study the consequences of high expression of DAPIT, we constructed a transgenic cell line that constitutively expressed DAPIT in human embryonal kidney cells, HEK293T. Enhanced DAPIT expression decreased mtDNA content and mitochondrial mass, and saturated respiratory chain by decreasing H+-ATP synthase activity. DAPIT over-expression also increased mitochondrial membrane potential and superoxide level, and translocated the transcription factors hypoxia inducible factor 1alpha (Hif1alpha) and beta-catenin to the nucleus. Accordingly, cells over-expressing DAPIT used more glucose and generated a larger amount of lactate compared to control cells. Interestingly, these changes were associated with an epithelial to mesenchymal (EMT)-like transition by changing E-cadherin to N-cadherin and up-regulating several key junction/adhesion proteins. At physiological level, DAPIT over-expression slowed down cell growth by G1 arrest and migration, and enhanced cell detachment. Several cancers also showed an increase in genomic copy number of Usmg5 (gene encoding DAPIT), thereby providing strong correlative evidence for DAPIT possibly having oncogenic function in cancers. CONCLUSIONS: DAPIT over-expression thus appears to modulate mitochondrial functions and alter cellular regulations, promote anaerobic metabolism and induce EMT-like transition. We propose that DAPIT over-expression couples the changes in mitochondrial metabolism to physiological and pathophysiological regulations, and suggest it could play a critical role in H+ ATP synthase dysfunctions. PMID- 26161957 TI - Mutations Causing Complex Disease May under Certain Circumstances Be Protective in an Epidemiological Sense. AB - Guided by the practice of classical epidemiology, research into the genetic basis of complex disease has usually taken for granted the dictum that causative mutations are invariably over-represented among clinically affected as compared to unaffected individuals. However, we show that this supposition is not true and that a mutation contributing to the etiology of a complex disease can, under certain circumstances, be depleted among patients. Populations with defined disease prevalence were repeatedly simulated under a Wright-Fisher model, assuming various types of population history and genotype-phenotype relationship. For each simulation, the resulting mutation-specific population frequencies and odds ratios (ORs) were evaluated. In addition, the relationship between mutation frequency and OR was studied using real data from the NIH GWAS catalogue of reported phenotype associations of single-nucleotide polymorphisms (SNPs). While rare diseases (prevalence <1%) were found to be consistently caused by rare mutations with ORs>1, up to 20% of mutations causing a pandemic disease (prevalence 10-20%) had ORs<1, and their population frequency ranged from 0% to 100%. Moreover, simulation-based ORs exhibited a wide distribution, irrespective of mutation frequency. In conclusion, a substantial proportion of mutations causing common complex diseases may appear 'protective' in genetic epidemiological studies and hence would normally tend to be excluded, albeit erroneously, from further study. This apparently paradoxical result is explicable in terms of mutual confounding of the respective genotype-phenotype relationships due to a negative correlation between causal mutations induced by their common gene genealogy. As would be predicted by our findings, a significant negative correlation became apparent in published genome-wide association studies between the OR of genetic variants associated with a particular disease and the prevalence of that disease. PMID- 26161958 TI - Nitrate and Nitrite Variability at the Seafloor of an Oxygen Minimum Zone Revealed by a Novel Microfluidic In-Situ Chemical Sensor. AB - Microfluidics, or lab-on-a-chip (LOC) is a promising technology that allows the development of miniaturized chemical sensors. In contrast to the surging interest in biomedical sciences, the utilization of LOC sensors in aquatic sciences is still in infancy but a wider use of such sensors could mitigate the undersampling problem of ocean biogeochemical processes. Here we describe the first underwater test of a novel LOC sensor to obtain in situ calibrated time-series (up to 40 h) of nitrate+nitrite (SigmaNOx) and nitrite on the seafloor of the Mauritanian oxygen minimum zone, offshore Western Africa. Initial tests showed that the sensor successfully reproduced water column (160 m) nutrient profiles. Lander deployments at 50, 100 and 170 m depth indicated that the biogeochemical variability was high over the Mauritanian shelf: The 50 m site had the lowest SigmaNOx concentration, with 15.2 to 23.4 MUM (median=18.3 MUM); while at the 100 site SigmaNOx varied between 21.0 and 30.1 MUM over 40 hours (median = 25.1 MUM). The 170 m site had the highest median SigmaNOx level (25.8 MUM) with less variability (22.8 to 27.7 MUM). At the 50 m site, nitrite concentration decreased fivefold from 1 to 0.2 MUM in just 30 hours accompanied by decreasing oxygen and increasing nitrate concentrations. Taken together with the time series of oxygen, temperature, pressure and current velocities, we propose that the episodic intrusion of deeper waters via cross-shelf transport leads to intrusion of nitrate-rich, but oxygen-poor waters to shallower locations, with consequences for benthic nitrogen cycling. This first validation of an LOC sensor at elevated water depths revealed that when deployed for longer periods and as a part of a sensor network, LOC technology has the potential to contribute to the understanding of the benthic biogeochemical dynamics. PMID- 26161959 TI - Effect of Water Invasion on Outburst Predictive Index of Low Rank Coals in Dalong Mine. AB - To improve the coal permeability and outburst prevention, coal seam water injection and a series of outburst prevention measures were tested in outburst coal mines. These methods have become important technologies used for coal and gas outburst prevention and control by increasing the external moisture of coal or decreasing the stress of coal seam and changing the coal pore structure and gas desorption speed. In addition, techniques have had a significant impact on the gas extraction and outburst prevention indicators of coal seams. Globally, low rank coals reservoirs account for nearly half of hidden coal reserves and the most obvious feature of low rank coal is the high natural moisture content. Moisture will restrain the gas desorption and will affect the gas extraction and accuracy of the outburst prediction of coals. To study the influence of injected water on methane desorption dynamic characteristics and the outburst predictive index of coal, coal samples were collected from the Dalong Mine. The methane adsorption/desorption test was conducted on coal samples under conditions of different injected water contents. Selective analysis assessed the variations of the gas desorption quantities and the outburst prediction index (coal cutting desorption index). Adsorption tests indicated that the Langmuir volume of the Dalong coal sample is ~40.26 m3/t, indicating a strong gas adsorption ability. With the increase of injected water content, the gas desorption amount of the coal samples decreased under the same pressure and temperature. Higher moisture content lowered the accumulation desorption quantity after 120 minutes. The gas desorption volumes and moisture content conformed to a logarithmic relationship. After moisture correction, we obtained the long-flame coal outburst prediction (cutting desorption) index critical value. This value can provide a theoretical basis for outburst prediction and prevention of low rank coal mines and similar occurrence conditions of coal seams. PMID- 26161960 TI - Novel Online Dimensionality Reduction Method with Improved Topology Representing and Radial Basis Function Networks. AB - This paper presents improvements to the conventional Topology Representing Network to build more appropriate topology relationships. Based on this improved Topology Representing Network, we propose a novel method for online dimensionality reduction that integrates the improved Topology Representing Network and Radial Basis Function Network. This method can find meaningful low dimensional feature structures embedded in high-dimensional original data space, process nonlinear embedded manifolds, and map the new data online. Furthermore, this method can deal with large datasets for the benefit of improved Topology Representing Network. Experiments illustrate the effectiveness of the proposed method. PMID- 26161961 TI - Brain Extraction Using Label Propagation and Group Agreement: Pincram. AB - Accurately delineating the brain on magnetic resonance (MR) images of the head is a prerequisite for many neuroimaging methods. Most existing methods exhibit disadvantages in that they are laborious, yield inconsistent results, and/or require training data to closely match the data to be processed. Here, we present pincram, an automatic, versatile method for accurately labelling the adult brain on T1-weighted 3D MR head images. The method uses an iterative refinement approach to propagate labels from multiple atlases to a given target image using image registration. At each refinement level, a consensus label is generated. At the subsequent level, the search for the brain boundary is constrained to the neighbourhood of the boundary of this consensus label. The method achieves high accuracy (Jaccard coefficient > 0.95 on typical data, corresponding to a Dice similarity coefficient of > 0.97) and performs better than many state-of-the-art methods as evidenced by independent evaluation on the Segmentation Validation Engine. Via a novel self-monitoring feature, the program generates the "success index," a scalar metadatum indicative of the accuracy of the output label. Pincram is available as open source software. PMID- 26161962 TI - Charge Transfer at Hybrid Interfaces: Plasmonics of Aromatic Thiol-Capped Gold Nanoparticles. AB - Although gold nanoparticles stabilized by organic thiols are the building blocks in a wide range of applications, the role of the ligands on the plasmon resonance of the metal core has been mostly ignored until now. Herein, a methodology based on the combination of spectroscopic ellipsometry and UV-vis spectroscopy is applied to extract dielectric functions of the different components. It is shown that aromatic thiols allow a significant charge transfer at the hybrid interface with the s and d bands of the gold core that yields "giant" red shifts of the plasmon band, up to 40 nm for spherical particles in the size range of 3-5 nm. These results suggest that hybrid nanoplasmonic devices may be designed through the suitable choice of metal core and organic components for optimized charge exchange. PMID- 26161963 TI - Glaucoma-related Changes in the Mechanical Properties and Collagen Micro architecture of the Human Sclera. AB - OBJECTIVE: The biomechanical behavior of the sclera determines the level of mechanical insult from intraocular pressure to the axons and tissues of the optic nerve head, as is of interest in glaucoma. In this study, we measure the collagen fiber structure and the strain response, and estimate the material properties of glaucomatous and normal human donor scleras. METHODS: Twenty-two posterior scleras from normal and diagnosed glaucoma donors were obtained from an eyebank. Optic nerve cross-sections were graded to determine the presence of axon loss. The specimens were subjected to pressure-controlled inflation testing. Full-field displacement maps were measured by digital image correlation (DIC) and spatially differentiated to compute surface strains. Maps of the collagen fiber structure across the posterior sclera of each inflated specimen were obtained using synchrotron wide-angle X-ray scattering (WAXS). Finite element (FE) models of the posterior scleras, incorporating a specimen-specific representation of the collagen structure, were constructed from the DIC-measured geometry. An inverse finite element analysis was developed to estimate the stiffness of the collagen fiber and inter-fiber matrix. RESULTS: The differences between glaucoma and non glaucoma eyes were small in magnitude. Sectorial variations of degree of fiber alignment and peripapillary scleral strain significantly differed between normal and diagnosed glaucoma specimens. Meridional strains were on average larger in diagnosed glaucoma eyes compared with normal specimens. Non-glaucoma specimens had on average the lowest matrix and fiber stiffness, followed by undamaged glaucoma eyes, and damaged glaucoma eyes but the differences in stiffness were not significant. CONCLUSION: The observed biomechanical and microstructural changes could be the result of tissue remodeling occuring in glaucoma and are likely to alter the mechanical environment of the optic nerve head and contribute to axonal damage. PMID- 26161965 TI - Co-Orientation: Quantifying Simultaneous Co-Localization and Orientational Alignment of Filaments in Light Microscopy. AB - Co-localization analysis is a widely used tool to seek evidence for functional interactions between molecules in different color channels in microscopic images. Here we extend the basic co-localization analysis by including the orientations of the structures on which the molecules reside. We refer to the combination of co-localization of molecules and orientational alignment of the structures on which they reside as co-orientation. Because the orientation varies with the length scale at which it is evaluated, we consider this scale as a separate informative dimension in the analysis. Additionally we introduce a data driven method for testing the statistical significance of the co-orientation and provide a method for visualizing the local co-orientation strength in images. We demonstrate our methods on simulated localization microscopy data of filamentous structures, as well as experimental images of similar structures acquired with localization microscopy in different color channels. We also show that in cultured primary HUVEC endothelial cells, filaments of the intermediate filament vimentin run close to and parallel with microtubuli. In contrast, no co orientation was found between keratin and actin filaments. Co-orientation between vimentin and tubulin was also observed in an endothelial cell line, albeit to a lesser extent, but not in 3T3 fibroblasts. These data therefore suggest that microtubuli functionally interact with the vimentin network in a cell-type specific manner. PMID- 26161967 TI - Look Up for Healing: Embodiment of the Heal Concept in Looking Upward. AB - OBJECTIVE: Conceptual processing may not be restricted to the mind. The heal concept has been metaphorically associated with an "up" bodily posture. Perceptual Symbol Systems (PSS) theory suggests that this association is underpinned by bodily states which occur during learning and become instantiated as the concept. Thus the aim of this study was to examine whether processing related to the heal concept is promoted by priming the bodily state of looking upwards. METHOD: We used a mixed 2x2 priming paradigm in which 58 participants were asked to evaluate words as either related to the heal concept or not after being primed to trigger the concept of looking up versus down (Direction--within subjects). A possible dose-response effect of priming was investigated via allocating participants to two 'strengths' of prime, observing an image of someone whose gaze was upward/downward (low strength) and observing an image of someone whose gaze was upward/downward while physically tilting their head upwards or downwards in accord with the image (high strength) (Strength--between subjects). RESULTS: Participants responded to words related to heal faster than words unrelated to heal across both "Strength" conditions. There was no evidence that priming was stronger in the high strength condition. CONCLUSION: The present study found that, consistent with a PSS view of cognition, the heal concept is embodied in looking upward, which has important implications for cognition, general health, health psychology, health promotion and therapy. PMID- 26161969 TI - Latent Alignment in Pathway-Dependent Ordering of Block Copolymer Thin Films. AB - Block copolymers spontaneously form well-defined nanoscale morphologies during thermal annealing. Yet, the structures one obtains can be influenced by nonequilibrium effects, including processing history or pathway-dependent assembly. Here, we explore various pathways for ordering of block copolymer thin films, using oven-annealing, as well as newly disclosed methods for rapid photothermal annealing and photothermal shearing. We report the discovery of an efficient pathway for ordering self-assembled films: ultrarapid shearing of as cast films induces "latent alignment" in the disordered morphology. Subsequent thermal processing can then develop this directly into a uniaxially aligned morphology with low defect density. This deeper understanding of pathway dependence may have broad implications in self-assembly. PMID- 26161966 TI - Cyclin Y Is Involved in the Regulation of Adipogenesis and Lipid Production. AB - A new member of the cyclin family cyclin Y (CCNY) is involved in the regulation of various physiological processes. In this study, the role of CCNY in energy metabolism was characterized. We found that compared with wild-type (WT) mice, Ccny knockout (KO) mice had both lower body weight and lower fat content. The Ccny KO mice also had a higher metabolic rate, resisted the stress of a high-fat diet, and were sensitive to calorie restriction. The expression levels of UCP1 and PGC1alpha were significantly higher in the brown adipose tissue (BAT) of the Ccny KO mice than that of the WT littermate controls, whereas there was no significant difference in BAT weight between the WT and the Ccny KO mice. In addition, the down-regulation of Ccny resulted in suppression of white adipocyte differentiation both in vivo and in vitro, while the expression of Ccny was up regulated by C/EBPalpha. Furthermore, both hepatocytes and HepG2 cells that were depleted of Ccny were insensitive to insulin stimulation, consistent with the significant inhibition of insulin sensitivity in the liver of the Ccny KO mice, but no significant changes in WAT and muscle, indicating that CCNY is involved in regulating the hepatic insulin signaling pathway. The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1) and fatty acid synthase (FASN). Together, these results provide a new link between CCNY and lipid metabolism in mice, and suggest that inhibition of CCNY may offer a therapeutic approach to obesity and diabetes. PMID- 26161970 TI - Structure Determination of Natural Products by Mass Spectrometry. AB - I review laboratory research on the development of mass spectrometric methodology for the determination of the structure of natural products of biological and medical interest, which I conducted from 1958 to the end of the twentieth century. The methodology was developed by converting small peptides to their corresponding polyamino alcohols to make them amenable to mass spectrometry, thereby making it applicable to whole proteins. The structures of alkaloids were determined by analyzing the fragmentation of a known alkaloid and then using the results to deduce the structures of related compounds. Heparin-like structures were investigated by determining their molecular weights from the mass of protonated molecular ions of complexes with highly basic, synthetic peptides. Mass spectrometry was also employed in the analysis of lunar material returned by the Apollo missions. A miniaturized gas chromatograph mass spectrometer was sent to Mars on board of the two Viking 1976 spacecrafts. PMID- 26161971 TI - A Thermal Mechanism of Ion Formation in MALDI. AB - An important recent discovery concerning the fundamentals of matrix-assisted laser desorption/ionization (MALDI) is that the abundance of each ion appearing in a spectrum is fixed, regardless of the experimental condition, when an effective temperature associated with the spectrum is fixed. We describe this phenomenon and the thermal picture for the ion formation in MALDI derived from it. Accepting that matrix-to-analyte proton transfer is in quasi-equilibrium as supported by experimental data, the above thermal determination occurs because the primary (matrix) ion formation processes are thermally governed. We propose that the abundances of the primary ions are limited by the autoprotolysis recombination process regardless of how they are initially produced. Finally, we note that primary ion formation, secondary (analyte) ion formation, and their dissociations occur sequentially while the effective temperature of the matrix plume falls steadily due to cooling associated with expansion. PMID- 26161972 TI - Evolution of Orbitrap Mass Spectrometry Instrumentation. AB - We discuss the evolution of Orbitrap mass spectrometry (MS) from its birth in the late 1990s to its current role as one of the most prominent techniques for MS. The Orbitrap mass analyzer is the first high-performance mass analyzer that employs trapping of ions in electrostatic fields. Tight integration with the ion injection process enables the high-resolution, mass accuracy, and sensitivity that have become essential for addressing analytical needs in numerous areas of research, as well as in routine analysis. We examine three major families of instruments (related to the LTQ Orbitrap, Q Exactive, and Orbitrap Fusion mass spectrometers) in the context of their historical development over the past ten eventful years. We discuss as well future trends and perspectives of Orbitrap MS. We illustrate the compelling potential of Orbitrap-based mass spectrometers as (ultra) high-resolution platforms, not only for high-end proteomic applications, but also for routine targeted analysis. PMID- 26161973 TI - Real-Time Monitoring of Critical Care Analytes in the Bloodstream with Chemical Sensors: Progress and Challenges. AB - We review approaches and challenges in developing chemical sensor-based methods to accurately and continuously monitor levels of key analytes in blood related directly to the status of critically ill hospitalized patients. Electrochemical and optical sensor-based technologies have been pursued to measure important critical care species in blood [i.e., oxygen, carbon dioxide, pH, electrolytes (K(+), Na(+), Cl(-), etc.), glucose, and lactate] in real-time or near real-time. The two main configurations examined to date for achieving this goal have been intravascular catheter sensors and patient attached ex vivo sensors with intermittent blood sampling via an attached indwelling catheter. We discuss the status of these configurations and the main issues affecting the accuracy of the measurements, including cell adhesion and thrombus formation on the surface of the sensors, sensor drift, sensor selectivity, etc. Recent approaches to mitigate these nagging performance issues that have prevented these technologies from clinical use are also discussed. PMID- 26161974 TI - Fe(III) Is Essential for Porcine Embryonic Development via Mitochondrial Function Maintenance. AB - Iron is an important trace element involved in several biological processes. The role of iron in porcine early embryonic development remains unknown. In the present study, we depleted iron (III, Fe3+) with deferoxamine (DFM), a specific Fe3+ chelator, in cultured porcine parthenotes and monitored embryonic development, apoptosis, mitochondrial membrane potential, and ATP production. Results showed biphasic function of Fe3+ in porcine embryo development. 0.5 MUM DFM obviously increased blastocyst formation (57.49 +/- 2.18% vs. control, 43.99 +/- 1.72%, P < 0.05) via reduced (P < 0.05) production of reactive oxygen species (ROS), further increased mitochondrial membrane potential and ATP production in blastocysts (P < 0.05). 0.5 MUM DFM decreased mRNA expression of Caspase 3 (Casp3) and increased Bcl-xL. However, results showed a significant reduction in blastocyst formation in the presence of 5.0 MUM DFM compared with the control group (DFM, 21.62 +/- 3.92% vs. control, 43.99 +/- 1.73%, P < 0.05). Fe3+ depletion reduced the total (DFM, 21.10 +/- 8.78 vs. control, 44.09 +/- 13.65, P < 0.05) and increased apoptotic cell number (DFM, 11.10 +/- 5.24 vs. control, 2.64 +/- 1.43, P < 0.05) in the blastocyst. An obvious reduction in mitochondrial membrane potential and ATP level after 5.0 MUM DFM treatment was observed. Co localization between mitochondria and cytochrome c was reduced after high concentration of DFM treatment. In conclusion, Fe3+ is essential for porcine embryonic development via mitochondrial function maintenance, but redundant Fe3+ impairs the function of mitochondria. PMID- 26161975 TI - Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice. AB - The mouse model of laser-induced choroidal neovascularization (CNV) has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model. PMID- 26161976 TI - Dual Roles of the Lysine-Rich Matrix Protein (KRMP)-3 in Shell Formation of Pearl Oyster, Pinctada fucata. AB - Matrix proteins play important roles in shell formation. Our group firstly isolated three cDNAs encoding lysine-rich matrix protein from Pinctada fucata in 2006. However, the functions of KRMPs are not fully understood. In addition, KRMPs contain two functional domains, the basic domain and the Gly/Tyr domain respectively. Based on the modular organization, the roles of their two domains were poorly characterized. Furthermore, KRMPs were then reported in other two species, P. maxima and P. margaritifera, which indicated that KRMPs might be very important for shell formation. In this study, the characterization and function of KRMP-3 and its two functional domains were studied in vitro through purification of recombinant glutathione S-transferase tagged KRMP-3 and two KRMP 3 deletion mutants. Western blot and immunofluorescence revealed that native KRMP 3 existed in the EDTA-insoluble matrix of the prismatic layer and was located in the organic sheet and the prismatic sheath. Recombinant KRMP-3 (rKRMP-3) bound tightly to chitin and this binding capacity was duo to the Gly/Tyr-rich region. rKRMP-3 inhibited the precipitation of CaCO3, affected the crystal morphology of calcite and inhibited the growth of aragonite in vitro, which was almost entirely attributed to the lysine-rich region. The results present direct evidence of the roles of KRMP-3 in shell biomineralization. The functional rBR region was found to participate in the growth control of crystals and the rGYR region was responsible to bind to chitin. PMID- 26161964 TI - A FDG-PET Study of Metabolic Networks in Apolipoprotein E epsilon4 Allele Carriers. AB - Recently, some studies have applied the graph theory in brain network analysis in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). However, relatively little research has specifically explored the properties of the metabolic network in apolipoprotein E (APOE) epsilon4 allele carriers. In our study, all the subjects, including ADs, MCIs and NCs (normal controls) were divided into 165 APOE epsilon4 carriers and 165 APOE epsilon4 noncarriers. To establish the metabolic network for all brain regions except the cerebellum, cerebral glucose metabolism data obtained from FDG-PET (18F-fluorodeoxyglucose positron emission tomography) were segmented into 90 areas with automated anatomical labeling (AAL) template. Then, the properties of the networks were computed to explore the between-group differences. Our results suggested that both APOE epsilon4 carriers and noncarriers showed the small-world properties. Besides, compared with APOE epsilon4 noncarriers, the carriers showed a lower clustering coefficient. In addition, significant changes in 6 hub brain regions were found in between-group nodal centrality. Namely, compared with APOE epsilon4 noncarriers, significant decreases of the nodal centrality were found in left insula, right insula, right anterior cingulate, right paracingulate gyri, left cuneus, as well as significant increases in left paracentral lobule and left heschl gyrus in APOE epsilon4 carriers. Increased local short distance interregional correlations and disrupted long distance interregional correlations were found, which may support the point that the APOE epsilon4 carriers were more similar with AD or MCI in FDG uptake. In summary, the organization of metabolic network in APOE epsilon4 carriers indicated a less optimal pattern and APOE epsilon4 might be a risk factor for AD. PMID- 26161977 TI - The Fingerprint of Anti-Bromodeoxyuridine Antibodies and Its Use for the Assessment of Their Affinity to 5-Bromo-2'-Deoxyuridine in Cellular DNA under Various Conditions. AB - We have developed a simple system for the analysis of the affinity of anti bromodeoxyuridine antibodies. The system is based on the anchored oligonucleotides containing 5-bromo-2'-deoxyuridine (BrdU) at three different positions. It allows a reliable estimation of the reactivity of particular clones of monoclonal anti-bromodeoxyuridine antibodies with BrdU in fixed and permeabilized cells. Using oligonucleotide probes and four different protocols for the detection of BrdU incorporated in cellular DNA, we identified two antibody clones that evinced sufficient reactivity to BrdU in all the tested protocols. One of these clones exhibited higher reactivity to 5-iodo-2' deoxyuridine (IdU) than to BrdU. It allowed us to increase the sensitivity of the used protocols without a negative effect on the cell physiology as the cytotoxicity of IdU was comparable with BrdU and negligible when compared to 5 ethynyl-2'-deoxyuridine. The combination of IdU and the improved protocol for oxidative degradation of DNA provided a sensitive and reliable approach for the situations when the low degradation of DNA and high BrdU signal is a priority. PMID- 26161980 TI - Efficiency of Polyoxometalate-Based Mesoporous Hybrids as Covalently Anchored Catalysts. AB - Polyoxometalate (POM) hybrids have been covalently immobilized through the formation of amide bonds on several types of mesoporous silica. This work allows the comparison of three POM-based mesoporous systems, obtained with three different silica supports in which either the organic functions of the support (amine vs carboxylic acid) and/or the structure of the support itself (SBA-15 vs mesocellular foams (MCF)) were varied. The resulting POM-based mesoporous systems have been studied in particular by high resolution transmission electronic microscopy (HR-TEM) in order to characterize the nanostructuration of the POMs inside the pores/cells of the different materials. We thus have shown that the best distribution and loading in POMs have been reached with SBA-15 functionalized with aminopropyl groups. In this case, the formation of amide bonds in the materials has led to the nonaggregation of the POMs inside the channels of the SBA-15. The catalytic activity of the anchored systems has been evaluated through the epoxidation of cyclooctene and cyclohexene with H2O2 in acetonitrile. The reactivity of the different grafted POMs hybrids has been compared to that in solution (homogeneous conditions). Parallels can be drawn between the distribution of the POMs and the activity of the supported systems. Furthermore, recycling tests together with catalyst filtration experiments during the reaction allowed us to preclude the hypothesis of a significant leaching of the supported catalyst. PMID- 26161978 TI - Using Whole Genome Analysis to Examine Recombination across Diverse Sequence Types of Staphylococcus aureus. AB - Staphylococcus aureus is an important clinical pathogen worldwide and understanding this organism's phylogeny and, in particular, the role of recombination, is important both to understand the overall spread of virulent lineages and to characterize outbreaks. To further elucidate the phylogeny of S. aureus, 35 diverse strains were sequenced using whole genome sequencing. In addition, 29 publicly available whole genome sequences were included to create a single nucleotide polymorphism (SNP)-based phylogenetic tree encompassing 11 distinct lineages. All strains of a particular sequence type fell into the same clade with clear groupings of the major clonal complexes of CC8, CC5, CC30, CC45 and CC1. Using a novel analysis method, we plotted the homoplasy density and SNP density across the whole genome and found evidence of recombination throughout the entire chromosome, but when we examined individual clonal lineages we found very little recombination. However, when we analyzed three branches of multiple lineages, we saw intermediate and differing levels of recombination between them. These data demonstrate that in S. aureus, recombination occurs across major lineages that subsequently expand in a clonal manner. Estimated mutation rates for the CC8 and CC5 lineages were different from each other. While the CC8 lineage rate was similar to previous studies, the CC5 lineage was 100-fold greater. Fifty known virulence genes were screened in all genomes in silico to determine their distribution across major clades. Thirty-three genes were present variably across clades, most of which were not constrained by ancestry, indicating horizontal gene transfer or gene loss. PMID- 26161979 TI - Impact of Compliance with a Care Bundle on Acute Kidney Injury Outcomes: A Prospective Observational Study. AB - BACKGROUND: A recent report has highlighted suboptimal standards of care for acute kidney injury (AKI) patients in England. The objective of this study was to ascertain if improvement in basic standard of care by implementing a care bundle (CB) with interruptive alert improved outcomes in patients with AKI. METHODS: An AKI CB linked to electronic recognition of AKI, coupled with an interruptive alert, was introduced to improve basic care delivered to patients with AKI. Outcomes were compared in patients who had the CB completed within 24 hours (early CB group) versus those who didn't have the CB completed or had it completed after 24 hours. RESULTS: In the 11-month period, 2297 patients had 2500 AKI episodes, with 1209 and 1291 episodes occurring before and after implementation of the AKI CB with interruptive alert, respectively. The CB was completed within 24 hours in 306 (12.2%) of AKI episodes. In-hospital case fatality was significantly lower in the early CB group (18% versus 23.1%, p 0.046). Progression to higher AKI stages was lower in the early CB group (3.9% vs. 8.1%, p 0.01). In multivariate analysis, patients in the early CB group had lower odds of death at discharge (0.641; 95% CI 0.46, 0.891), 30 days (0.707; 95% CI 0.527, 0.950), 60 days (0.704; 95% CI 0.526, 0.941) and after a median of 134 days (0.771; 95% CI 0.62, 0.958). CONCLUSIONS: Compliance with AKI CB was associated with a decrease in case-fatality and reduced progression to higher AKI stage. Further interventions are required to improve utilization of the CB. PMID- 26161981 TI - Testing the Effectiveness of Environmental Variables to Explain European Terrestrial Vertebrate Species Richness across Biogeographical Scales. AB - We compared the effectiveness of environmental variables, and in particular of land-use indicators, to explain species richness patterns across taxonomic groups and biogeographical scales (i.e. overall pan-Europe and ecoregions within pan Europe). Using boosted regression trees that handle non-linear relationships, we compared the relative influence (as a measure of effectiveness) of environmental variables related to climate, landscape (or habitat heterogeneity), land-use intensity or energy availability to explain European vertebrate species richness (birds, amphibians, and mammals) at the continental and ecoregion scales. We found that dominant land cover and actual evapotranspiration that relate to energy availability were the main correlates of vertebrate species richness over Europe. At the ecoregion scale, we identified four distinct groups of ecoregions where species richness was essentially associated to (i) seasonality of temperature, (ii) actual evapotranspiration and/or mean annual temperature, (iii) seasonality of precipitation, actual evapotranspiration and land cover) and (iv) and an even combination of the environmental variables. This typology of ecoregions remained valid for total vertebrate richness and the three vertebrate groups taken separately. Despite the overwhelming influence of land cover and actual evapotranspiration to explain vertebrate species richness patterns at European scale, the ranking of the main correlates of species richness varied between regions. Interestingly, landscape and land-use indicators did not stand out at the continental scale but their influence greatly increased in southern ecoregions, revealing the long-lasting human footprint on land-use-land-cover changes. Our study provides one of the first multi-scale descriptions of the variability in the ranking of correlates across several taxa. PMID- 26161983 TI - A Pd24 Pregnant Molecular Nanoball: Self-Templated Stellation by Precise Mapping of Coordination Sites. AB - We found that Pd(II) ion (M) and the smallest 120 degrees bidentate donor pyrimidine (L(a)) self-assemble into a mononuclear M(L(a))4 complex (1a) instead of the expected smallest M12(L(a))24 molecular ball (1), presumably due to the weak coordination nature of the pyrimidine. To construct such a pyrimidine bridged nanoball, we employed a new donor tris(4-(pyrimidin-5-yl)phenyl)amine (L); which upon selective complexation with Pd(II) ions resulted in the formation of a pregnant M24L24 molecular nanoball (2) consisting of a pyrimidine-bridged Pd12 baby-ball supported by a Pd12 larger mother-ball. The formation of the baby ball was not successful without the support of the mother-ball. Thus, we created an example of a self-assembly where the inner baby-ball resembling to the predicted M12(L(a))24 ball (1) was incarcerated by the giant outer mother-ball by means of geometrical constraints. Facile conversion of the pregnant ball 2 to a smaller M12(L(b))24 ball 3 with dipyridyl donor was achieved in a single step. PMID- 26161982 TI - Epinephrine Activation of the beta2-Adrenoceptor Is Required for IL-13-Induced Mucin Production in Human Bronchial Epithelial Cells. AB - Mucus hypersecretion by airway epithelium is a hallmark of inflammation in allergic asthma and results in airway narrowing and obstruction. Others have shown that administration a TH2 cytokine, IL-13 is sufficient to cause mucus hypersecretion in vivo and in vitro. Asthma therapy often utilizes beta2 adrenoceptor (beta2AR) agonists, which are effective acutely as bronchodilators, however chronic use may lead to a worsening of asthma symptoms. In this study, we asked whether beta2AR signaling in normal human airway epithelial (NHBE) cells affected mucin production in response to IL-13. This cytokine markedly increased mucin production, but only in the presence of epinephrine. Mucin production was blocked by ICI-118,551, a preferential beta2AR antagonist, but not by CGP-20712A, a preferential beta1AR antagonist. Constitutive beta2AR activity was not sufficient for IL-13 induced mucin production and beta-agonist-induced signaling is required. A clinically important long-acting beta-agonist, formoterol, was as effective as epinephrine in potentiating IL-13 induced MUC5AC transcription. IL 13 induced mucin production in the presence of epinephrine was significantly reduced by treatment with selective inhibitors of ERK1/2 (FR180204), p38 (SB203580) and JNK (SP600125). Replacement of epinephrine with forskolin + IBMX resulted in a marked increase in mucin production in NHBE cells in response to IL 13, and treatment with the inhibitory cAMP analogue Rp-cAMPS decreased mucin levels induced by epinephrine + IL-13. Our findings suggest that beta2AR signaling is required for mucin production in response to IL-13, and that mitogen activated protein kinases and cAMP are necessary for this effect. These data lend support to the notion that beta2AR-agonists may contribute to asthma exacerbations by increasing mucin production via activation of beta2ARs on epithelial cells. PMID- 26161985 TI - Measurement of Crystalline Lens Volume During Accommodation in a Lens Stretcher. AB - PURPOSE: To determine if the lens volume changes during accommodation. METHODS: The study used data acquired on 36 cynomolgus monkey lenses that were stretched in a stepwise fashion to simulate disaccommodation. At each step, stretching force and dioptric power were measured and a cross-sectional image of the lens was acquired using an optical coherence tomography system. Images were corrected for refractive distortions and lens volume was calculated assuming rotational symmetry. The average change in lens volume was calculated and the relation between volume change and power change, and between volume change and stretching force, were quantified. Linear regressions of volume-power and volume-force plots were calculated. RESULTS: The mean (+/- SD) volume in the unstretched (accommodated) state was 97 +/- 8 mm3. On average, there was a small but statistically significant (P = 0.002) increase in measured lens volume with stretching. The mean change in lens volume was +0.8 +/- 1.3 mm3. The mean volume power and volume-load slopes were -0.018 +/- 0.058 mm3/D and +0.16 +/- 0.40 mm3/g. CONCLUSIONS: Lens volume remains effectively constant during accommodation, with changes that are less than 1% on average. This result supports a hypothesis that the change in lens shape with accommodation is accompanied by a redistribution of tissue within the capsular bag without significant compression of the lens contents or fluid exchange through the capsule. PMID- 26161984 TI - Nitrite Modification of Extracellular Matrix Alters CD46 Expression and VEGF Release in Human Retinal Pigment Epithelium. AB - PURPOSE: Loss of CD46 has recently been implicated in choroidal neovascularization in mice. Herein we investigated the effect of nitrite modification of the extracellular matrix (ECM) as an in vitro model of "aging" and its effect on CD46 expression and vascular endothelial growth factor (VEGF) release in cocultured human retinal pigment epithelium (RPE). METHODS: ARPE-19 cells were plated onto RPE-derived ECM conditions (untreated; nitrite modified; nitrite modified followed by washing with Triton X-100; or nitrite modified followed by washing with Triton X-100 and coated with extracellular matrix ligands). Cells were cultured for 7 days and CD46 expression was analyzed by immunohistochemistry and Western blot. Additionally, CD46 short interfering RNA (siRNA) was transfected into ARPE-19 cells, and VEGF levels were determined by ELISA. Finally, in the same ECM conditions, ARPE-19 cells were challenged with normal human serum and VEGF levels determined by ELISA. RESULTS: CD46 is expressed on the basolateral surface of ARPE-19 cells on RPE-derived ECM. Nitrite modification of ECM reduced the expression of CD46 on ARPE-19 cells by 0.5-fold (P = 0.003) and increased VEGF release in ARPE-19 cells by 1.7-fold (P < 0.001). CD46 knockdown also increased release of VEGF on the apical and basal sides of ARPE-19 cells in culture by 1.3- (P = 0.012) and 1.2-fold (P = 0.017), respectively. CONCLUSIONS: Nitrite modification of the ECM decreased CD46 expression and increased the release of VEGF from ARPE-19 cells. Changes in CD46 expression may lead to changes in VEGF and play a pathologic role in the development of age-related macular degeneration. PMID- 26161986 TI - Toward New Engagement Paradigms For Intraocular Lenses: Light-Initiated Bonding of Capsular Bag to Lens Materials. AB - PURPOSE: Successful intraocular lens procedures, that is, implantation of accommodating intraocular lenses (A-IOL), require firm engagement of the IOL haptics to the capsular bag. We evaluated the use of photochemical bonding to engage IOL materials to the capsular bag. METHODS: Freshly enucleated eyes of New Zealand rabbits were used in two types of photobonding experiments using Rose Bengal (RB) photoinitiation and green light (532-nm) irradiation. First, RB stained capsular bag strips were photobonded ex vivo to IOL polymer [poly(2 hydroxyethyl methacrylate) pHEMA] strips in an atmosphere of air and of nitrogen. Second, IOLs were implanted intracapsularly and photobonded intraocularly. Irradiation times were between 30 and 180 seconds, and laser irradiance was between 0.25 and 0.65 W/cm(2). The strength of the bonding was tested using a custom-developed uniaxial extensiometry system and the breakage load (the load that caused breakage per bonded area) was calculated. RESULTS: The breakage load of ex vivo capsule-pHEMA bonds increased exponentially with irradiation time, using 0.45 W/cm(2). In air, the average breakage load across all conditions was 1 g/mm(2) and 1.6 times lower than that in a nitrogen atmosphere. Intraocularly, RB stained IOLs were strongly photobonded to the capsule bag with breakage loads > 0.8 g/mm(2). CONCLUSIONS: Breakage of the photobonded linkage between IOL material and capsular bag required loads substantially greater than the maximum force of ciliary muscle, suggesting that this technology may introduce a new paradigm for engagement of A-IOLs. The bonding produced in air was stronger than that in nitrogen atmosphere, suggesting that oxygen is involved in the chemical mechanism for photobonding. PMID- 26161987 TI - Axonal Transport in the Rat Optic Nerve Following Short-Term Reduction in Cerebrospinal Fluid Pressure or Elevation in Intraocular Pressure. AB - PURPOSE: To examine the influence of short-term reduction in cerebrospinal fluid pressure (CSFP) as compared with short-term elevation in IOP on axonal transport. METHODS: The study included 111 adult Sprague-Dawley rats. For 6 hours, IOP was unilaterally elevated to 40 mm Hg (IOP40-group; n = 27), IOP was unilaterally increased to a value of 25 mm Hg below the mean blood pressure (PP25-group; n = 27), or CSFP was reduced by continuous aspiration of cerebrospinal fluid (Low CSFP-group; n = 27). A sham control group (with a trocar in cisterna magna without cerebrospinal fluid release) included 24 rats. The left eyes of the IOP40 study group and PP25 study group served as additional contralateral control group. Orthograde axonal transport was examined by intravitreally injected rhodamine-beta-isothiocyanate; retrograde axoplasmic flow was assessed by fluorogold injected into the superior colliculi. RESULTS: At 24 hours after baseline, rhodamine-beta-isothiocyanate (RITC) staining intensity of the optic nerve was lower (P < 0.05) in the IOP40-group, PP25-group, and Low-CSFP-group than in the control groups. At 6 hours after the fluorogold injection, fluorogold fluorescence was significantly lower in the IOP40-group, the PP25-group, and the Low-CSFP-group than in the control groups. At 5 days after baseline, the fluorogold fluorescence no longer differed significantly between the IOP40-group or the Low-CSFP-group and the control groups. At 1 week after baseline, retinal ganglion cell density was markedly reduced only in the PP25-group. CONCLUSIONS: Both short-term lowering of CSFP and short-term rise in IOP were associated with a disturbance of both the orthograde and retrograde axonal transport. The findings support the notion of an association between abnormally low CSFP and optic nerve damage. PMID- 26161988 TI - Foveal Sparing of Reticular Drusen in Eyes With Early and Intermediate Age Related Macular Degeneration. AB - PURPOSE: To analyze the central distribution of reticular drusen (RDR) in eyes with early and intermediate AMD without soft drusen or pigmentary changes within the central subfield using confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT). METHODS: Fifty-two eyes of 46 subjects (median age: 76.3 years, interquartile range [IQR], 71-80) were examined by simultaneous combined near-infrared cSLO and raster SD-OCT imaging. The appearance and the topographic distribution of RDR were analyzed within the macula area using the Early Treatment Diabetic Retinopathy Study grid. In addition, longitudinal examinations during an observation period of at least 6 months were included (median observation time: 1.5 years, IQR, 0.9-2.8). RESULTS: The RDR involvement within the central subfield (46%) was less compared with the surrounding subfields (62%-100%), slices (67%-100%), and zones (94%-100%) (P < 0.001). RDR were typically distributed as one continuous zone around the fovea in an incomplete or complete ring-shaped pattern, whereas the fovea itself was either spared or only a few lesions were present. Over time, the RDR density increased and new RDR lesions occurred at the border of the RDR zone toward a closure of the ring-shaped pattern. Within the fovea, development of RDR was observed in 8 of 28 eyes. CONCLUSIONS: The fovea appears to be less vulnerable to RDR development as compared with peripheral macula areas. Factors for initial sparing of the foveal retina are yet unknown but may relate to topographic differences of choroidal blood flow and/or photoreceptor distribution. PMID- 26161989 TI - Corneal Shape, Volume, and Interocular Symmetry: Parameters to Optimize the Design of Biosynthetic Corneal Substitutes. AB - PURPOSE: To characterize the three-dimensional (3D) shape, volume distribution, and mirror symmetry of the right and left corneas at the scale of a large population, based on the integrated analysis of 3D corneal shape average maps and topography parameters. METHODS: A total of 7670 Orbscan II corneal topographies from 3835 consenting subjects with no history of ocular disease were studied. Average topography maps were created using the right and left corneal topographies of all subjects. To quantify symmetry, left eye topographies were flipped horizontally into "right eye" topographies and statistics maps were generated, including difference and intraclass correlation coefficient (ICC) maps. RESULTS: The standard deviation of the anterior and posterior average elevation maps in the 3-mm radius central zone of the right and left corneas ranged within +/- 8 MUm and +/- 44 MUm, respectively. The ICC maps showed almost perfect interocular agreement for anterior elevation, posterior elevation, and pachymetry (all ICCs > 0.96). All studied shape parameters also showed excellent agreement (ICCs >= 0.80). Mirror symmetry was not affected by age, sex, or spherical equivalent. We also showed that this horizontal reflection (flip) of the right and left corneal shapes could not be replaced by a simple rotation. CONCLUSIONS: These results indicate that in normal eyes, the anterior elevation, posterior elevation, and pachymetry of the right and left corneas show remarkable symmetry. This comprehensive analysis was achieved with the purpose of guiding the development of future biosynthetic corneal substitutes. PMID- 26161990 TI - Global Visit Effects in Point-Wise Longitudinal Modeling of Glaucomatous Visual Fields. AB - PURPOSE: One of the difficulties in modeling visual field (VF) data is the sometimes large and correlated measurement errors in the point-wise sensitivity estimates. As these errors affect all locations of the same VF, we propose to model them as global visit effects (GVE). We evaluate this model and show the effect it has on progression estimation and prediction. METHODS: Visual field series (24-2 Full Threshold; 15 biannual VFs per patient) of 125 patients with primary glaucoma were included in the analysis. The contribution of the GVE was evaluated by comparing the fitting and predictive ability of a conventional model, which does not contain GVE, to such a model that incorporates the GVE. Moreover, the GVE's effect on the estimated slopes was evaluated by determining the absolute difference between the slopes of the models. Finally, the magnitude of the GVE was compared with that of other measurement errors. RESULTS: The GVE model showed a significant improvement in both the model fit and predictive ability over the conventional model, especially when the number of VFs in a series is limited. The average absolute difference in slopes between the models was 0.13 dB/y. Lastly, the magnitude of the GVE was more than three times larger than the measureable factors combined. CONCLUSIONS: By incorporating the GVE in the longitudinal modeling of VF data, better estimates may be obtained of the rate of progression as well as of predicted future sensitivities. PMID- 26161992 TI - Enhancement of resistive switching under confined current path distribution enabled by insertion of atomically thin defective monolayer graphene. AB - Resistive random access memory (ReRAM) devices have been extensively investigated resulting in significant enhancement of switching properties. However fluctuations in switching parameters are still critical weak points which cause serious failures during 'reading' and 'writing' operations of ReRAM devices. It is believed that such fluctuations may be originated by random creation and rupture of conducting filaments inside ReRAM oxides. Here, we introduce defective monolayer graphene between an oxide film and an electrode to induce confined current path distribution inside the oxide film, and thus control the creation and rupture of conducting filaments. The ReRAM device with an atomically thin interlayer of defective monolayer graphene reveals much reduced fluctuations in switching parameters compared to a conventional one. Our results demonstrate that defective monolayer graphene paves the way to reliable ReRAM devices operating under confined current path distribution. PMID- 26161991 TI - Metabolic Syndrome without Diabetes or Hypertension Still Necessitates Early Screening for Chronic Kidney Disease: Information from a Chinese National Cross Sectional Study. AB - Metabolic syndrome (MS) is prevalent, with an increasing contribution to the incidence of chronic kidney disease (CKD). The study of the relationship between them is important. The CKD survey, a national cross-sectional study, provided a large database to accomplish this study. The study population were 41 131 adults from this survey between 2008 and 2009. CKD was defined as estimate glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 or the presence of albuminuria. MS was diagnosed by National Cholesterol Education Program-Adult Treatment Panel III (ATPIII), ATPIII-modified or International Diabetes Federation (IDF) criteria. Logistic regression model was applied to study the impact of MS or its components on CKD or its components. The age and sex standardized prevalence of MS by ATPIII, ATPIII-modified and IDF criteria was 11.77% (11.13%-12.40%), 21.51% (20.69%-22.34%) and 16.67% (15.92-17.42)% respectively. Multivariate logistic regression models showed that MS and its components were associated with higher CKD prevalence. The risk for CKD and its components increased with the number of MS components. After adjusting for hypertension and diabetes, the odds ratios of MS for CKD decreased, but remained significantly more than 1 between 1.16(95%CI 1.07-1.26) and 1.37 (95% CI 1.25 1.50) across the different models. Similar results were found with albuminuria, while for decreased eGFR, after adjusting for hypertension and diabetes, the odds ratios of MS and MS components (except elevated TG) became insignificant. In conclusion, MS is prevalent and associated with a higher prevalence of CKD. Different MS components are associated with different risks for CKD, even after adjusting for hypertension and diabetes, which may mainly be contributed more by the increased risk for albuminuria than that for decreased eGFR. More attention must be paid to the population with MS, including those with elevated blood pressure and serum glucose. PMID- 26161993 TI - Effect of lipid profile on prognosis in the patients with amyotrophic lateral sclerosis: Insights from the olesoxime clinical trial. AB - Patients with ALS may have insufficientenergy substrates, due to dysphagia and hypermetabolism, which adversely affects the prognosis. Hyperlipidaemia has been reported to be associated with ALS and to represent a significant prognostic factor for survival in ALS. The aim of this study was to examine the prevalence of dyslipidaemia among a cohort of patients with ALS and how the lipid profile of patients with ALS influenced the prognosis. This was a prospective observational cohort study comprising 512 ALS patients, recruited for the TRO19622 (Olesoxime) investigational medicinal product trial. Fasting serum concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured as part of routine monitoring in the trial. Seventy-three percent of the participants had hypercholesterolaemia (defined as total cholesterol >= 5.1 mmol/l) at the screening visit. The prevalence of hypercholesterolaemia decreased with time and was 64% at 18 months follow-up. On unadjusted analysis total cholesterol, LDL-C and LDL/HDL ratio had a statistically significant effect on survival (p = 0.015, 0.003 and 0.027, respectively). When adjusted for prognostic covariates, however, none of the lipid measures was found to have a statistically significant effect on survival. In conclusion, prognosis in ALS is not influenced by the lipid profile of patients. PMID- 26161994 TI - Approximate Counting of Graphical Realizations. AB - In 1999 Kannan, Tetali and Vempala proposed a MCMC method to uniformly sample all possible realizations of a given graphical degree sequence and conjectured its rapidly mixing nature. Recently their conjecture was proved affirmative for regular graphs (by Cooper, Dyer and Greenhill, 2007), for regular directed graphs (by Greenhill, 2011) and for half-regular bipartite graphs (by Miklos, Erdos and Soukup, 2013). Several heuristics on counting the number of possible realizations exist (via sampling processes), and while they work well in practice, so far no approximation guarantees exist for such an approach. This paper is the first to develop a method for counting realizations with provable approximation guarantee. In fact, we solve a slightly more general problem; besides the graphical degree sequence a small set of forbidden edges is also given. We show that for the general problem (which contains the Greenhill problem and the Miklos, Erdos and Soukup problem as special cases) the derived MCMC process is rapidly mixing. Further, we show that this new problem is self-reducible therefore it provides a fully polynomial randomized approximation scheme (a.k.a. FPRAS) for counting of all realizations. PMID- 26161995 TI - An Outbreak of Chikungunya in Rural Bangladesh, 2011. AB - BACKGROUND: The first identified Chikungunya outbreak occurred in Bangladesh in 2008. In late October 2011, a local health official from Dohar Sub-district, Dhaka District, reported an outbreak of undiagnosed fever and joint pain. We investigated the outbreak to confirm the etiology, describe the clinical presentation, and identify associated vectors. METHODOLOGY: During November 2-21, 2011, we conducted house-to-house surveys to identify suspected cases, defined as any inhabitant of Char Kushai village with fever followed by joint pain in the extremities with onset since August 15, 2011. We collected blood specimens and clinical histories from self-selected suspected cases using a structured questionnaire. Blood samples were tested for IgM antibodies against Chikungunya virus. The village was divided into nine segments and we collected mosquito larvae from water containers in seven randomly selected houses in each segment. We calculated the Breteau index for the village and identified the mosquito species. RESULTS: The attack rate was 29% (1105/3840) and 29% of households surveyed had at least one suspected case: 15% had >=3. The attack rate was 38% (606/1589) in adult women and 25% in adult men (320/1287). Among the 1105 suspected case-patients, 245 self-selected for testing and 80% of those (196/245) had IgM antibodies. In addition to fever and joint pain, 76% (148/196) of confirmed cases had rash and 38%(75/196) had long-lasting joint pain. The village Breteau index was 35 per 100 and 89%(449/504) of hatched mosquitoes were Aedes albopictus. CONCLUSION: The evidence suggests that this outbreak was due to Chikungunya. The high attack rate suggests that the infection was new to this area, and the increased risk among adult women suggests that risk of transmission may have been higher around households. Chikungunya is an emerging infection in Bangladesh and current surveillance and prevention strategies are insufficient to mount an effective public health response. PMID- 26161996 TI - Efficient Identification of Murine M2 Macrophage Peptide Targeting Ligands by Phage Display and Next-Generation Sequencing. AB - Peptide ligands are used to increase the specificity of drug carriers to their target cells and to facilitate intracellular delivery. One method to identify such peptide ligands, phage display, enables high-throughput screening of peptide libraries for ligands binding to therapeutic targets of interest. However, conventional methods for identifying target binders in a library by Sanger sequencing are low-throughput, labor-intensive, and provide a limited perspective (<0.01%) of the complete sequence space. Moreover, the small sample space can be dominated by nonspecific, preferentially amplifying "parasitic sequences" and plastic-binding sequences, which may lead to the identification of false positives or exclude the identification of target-binding sequences. To overcome these challenges, we employed next-generation Illumina sequencing to couple high throughput screening and high-throughput sequencing, enabling more comprehensive access to the phage display library sequence space. In this work, we define the hallmarks of binding sequences in next-generation sequencing data, and develop a method that identifies several target-binding phage clones for murine, alternatively activated M2 macrophages with a high (100%) success rate: sequences and binding motifs were reproducibly present across biological replicates; binding motifs were identified across multiple unique sequences; and an unselected, amplified library accurately filtered out parasitic sequences. In addition, we validate the Multiple Em for Motif Elicitation tool as an efficient and principled means of discovering binding sequences. PMID- 26161997 TI - Multifocal Papillary Thyroid Cancer Increases the Risk of Central Lymph Node Metastasis. AB - BACKGROUND: Papillary thyroid cancer (PTC) is the most common thyroid malignancy, with a strong predilection for lymph node metastasis, most commonly to the central neck compartment (level VI). Few studies have evaluated lymph node metastasis in multifocal PTC, and the role of level VI dissection in the management of PTC remains controversial. This retrospective analysis evaluated the rate of level VI lymph node positivity in multifocal PTC, as compared with unifocal disease, in order to inform surgical decision making better. METHODS: Patients with PTC who underwent total or hemi-thyroidectomy plus level VI lymph node dissection at the authors' institution between January 2008 and June 2014 were included (N=227). The number and laterality of PTC foci, lymphovascular invasion (LVI), extrathyroidal extension (ETE), and positive/total number of level VI lymph nodes were recorded. Fisher's exact test was used to determine univariate associations, and multivariate analysis was done by logistical regression. RESULTS: There was an association between the number of PTC foci and level VI node positivity (p<0.001), with an odds ratio (OR) of 2.355 in patients with three or more tumor foci (p=0.026). The OR for central neck metastasis was 1.088 with each additional focus of PTC (p=0.018). The risk of level VI node positivity in the presence of one or two foci was only 19%, with no appreciable difference between one and two foci. This risk increased in the presence of between three and nine foci (38%), and 10 or more foci (88%). Level VI node positivity was associated with ETE (p<0.001), LVI (p<0.001), and size of the largest focus (p<0.001). There was no association between level VI lymph node positivity and male sex (p=0.089), bilaterality (p=0.276), or age (p=0.076). CONCLUSIONS: There is a significant association between multifocal PTC and level VI lymph node positivity, increasing proportionally with the number of foci. These findings recognize multifocality as a sign of tumor aggressiveness, as evidenced by a higher propensity for lymph node metastasis. PMID- 26161998 TI - Growth Arrest Specific 1 (Gas1) Gene Overexpression in Liver Reduces the In Vivo Progression of Murine Hepatocellular Carcinoma and Partially Restores Gene Expression Levels. AB - The prognosis of hepatocellular carcinoma patients is usually poor, the size of tumors being a limiting factor for surgical treatments. Present results suggest that the overexpression of Gas1 (growth arrest specific 1) gene reduces the size, proliferating activity and malignancy of liver tumors. Mice developing diethylnitrosamine-induced hepatocellular carcinoma were subjected to hydrodynamic gene delivery to overexpress Gas1 in liver. This treatment significantly (p < 0.05) reduced the number of large tumors, while the difference in the total number of lesions was not significant. Moreover, the number of carcinoma foci in the liver and the number of lung metastases were reduced. These results are related with the finding that overexpression of Gas1 in Hepa 1-6 cells arrests cell cycle before S phase, with a significant (p < 0.01) and concomitant reduction in the expression of cyclin E2 gene. In addition, a triangular analysis of microarray data shows that Gas1 overexpression restores the transcription levels of 150 genes whose expression was affected in the diethylnitrosamine-induced tumors, thirteen of which are involved in the hedgehog signaling pathway. Since the in vivo Gas1 gene delivery to livers of mice carrying hepatocellular carcinoma reduces the size and proliferating activity of tumors, partially restoring the transcriptional profile of the liver, the present study opens promising insights towards a therapeutic approach for hepatocellular carcinoma. PMID- 26161999 TI - The Chaperoning Activity of Amino-oxyacetic Acid on Folding-Defective Variants of Human Alanine:Glyoxylate Aminotransferase Causing Primary Hyperoxaluria Type I. AB - The rare disease Primary Hyperoxaluria Type I (PH1) results from the deficit of liver peroxisomal alanine:glyoxylate aminotransferase (AGT), as a consequence of inherited mutations on the AGXT gene frequently leading to protein misfolding. Pharmacological chaperone (PC) therapy is a newly developed approach for misfolding diseases based on the use of small molecule ligands able to promote the correct folding of a mutant enzyme. In this report, we describe the interaction of amino-oxyacetic acid (AOA) with the recombinant purified form of two polymorphic species of AGT, AGT-Ma and AGT-Mi, and with three pathogenic variants bearing previously identified folding defects: G41R-Ma, G170R-Mi, and I244T-Mi. We found that for all these enzyme AOA (i) forms an oxime at the active site, (ii) behaves as a slow, tight-binding inhibitor with KI values in the nanomolar range, and (iii) increases the thermal stability. Furthermore, experiments performed in mammalian cells revealed that AOA acts as a PC by partly preventing the intracellular aggregation of G41R-Ma and by promoting the correct peroxisomal import of G170R-Mi and I244T-Mi. Based on these data, we carried out a small-scale screening campaign. We identified four AOA analogues acting as AGT inhibitors, even if only one was found to act as a PC. The possible relationship between the structure and the PC activity of these compounds is discussed. Altogether, these results provide the proof-of-principle for the feasibility of a therapy with PCs for PH1-causing variants bearing folding defects and provide the scaffold for the identification of more specific ligands. PMID- 26162000 TI - Do Payments Pay Off? Evidence from Participation in Costa Rica's PES Program. AB - Payments for environmental services (PES) are often viewed as a way to simultaneously improve conservation outcomes and the wellbeing of rural households who receive the payments. However, evidence for such win-win outcomes has been elusive. We add to the growing literature on conservation program impacts by using primary household survey data to evaluate the socioeconomic impacts of participation in Costa Rica's PES program. Despite the substantial cash transfers to voluntary participants in this program, we do not detect any evidence of impacts on their wealth or self-reported well-being using a quasi experimental design. These results are consistent with the common claim that voluntary PES do not harm participants, but they beg the question of why landowners participate if they do not benefit. Landowners in our sample voluntarily renewed their contracts after five years in the program and thus are unlikely to have underestimated their costs of participation. They apparently did not invest additional income from the program in farm inputs such as cattle or hired labor, since both decreased as a result of participation. Nor do we find evidence that participation encouraged moves off-farm. Instead, semi-structured interviews suggest that participants joined the program to secure their property rights and contribute to the public good of forest conservation. Thus, in order to understand the social impacts of PES, we need to look beyond simple economic rationales and material outcomes. PMID- 26162001 TI - Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches. AB - It is alarming that only 59% of those who have post-traumatic stress disorder (PTSD) respond to selective serotonin reuptake inhibitors. Many existing treatments, both pharmacological and nonpharmacological, do not directly target trauma memories that lay at the core of the PTSD pathogenesis. Notable exceptions are medications like ketamine and propranolol and trauma-focused psychotherapies like eye-movement desensitization and reprocessing therapy (developed by Shapiro) and Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) for trauma memories (developed by Pradhan). Although the antidepressant effects of ketamine are no longer news, ketamine's effects on treatment refractory PTSD (TR-PTSD) is a recent concept. As TR-PTSD has a marked public health burden and significant limitations in terms of treatment interventions, a thorough assessment of current strategies is required. Research to bring clarity to the underlying pathophysiology and neurobiology of TR-PTSD delineating the chemical, structural, and circuitry abnormalities will take time. In the interim, in the absence of a 1-size-fits-all therapeutic approach, pragmatically parallel lines of research can be pursued using the pharmacological and nonpharmacological treatments that have a strong theoretical rationale for efficacy. This article aims to review the current literature on interventions for PTSD, most notably ketamine, trans-cranial magnetic stimulation treatment, yoga and mindfulness interventions, and TIMBER. We present an outline for their future use, alone as well as in combination, with a hope of providing additional insights as well as advocating for developing more effective therapeutic intervention for this treatment-resistant and debilitating condition. PMID- 26162002 TI - Use of an automated PCR assay, the GenomEra S. pneumoniae, for rapid detection of Streptococcus pneumoniae in blood cultures. AB - BACKGROUND: Streptococcus pneumoniae is recognized as a major cause of pneumonia, meningitis, and bacteremia. Since the mortality rate for pneumococcal bacteremia remains high, the reliable detection of the bacterium in blood samples is important. In this study, the performance of a new automated PCR assay, the GenomEra(TM) S. pneumoniae, for direct detection of S. pneumoniae in blood cultures was investigated. METHODS: In total, 200 samples were analyzed, including 90 previously identified culture collection isolates and 110 blood culture specimens. The species identification was confirmed with routine diagnostic methods including MALDI-TOF or 16S rDNA sequencing. RESULTS: From culture collection, the GenomEra S. pneumoniae assay correctly identified all 37 S. pneumoniae isolates consisting of 18 different serotypes, while all 53 non-S. pneumoniae isolates yielded negative test results. Of 110 blood culture specimens, 46 grew S. pneumoniae and all were positive by the GenomEra assay direct from bottle. The detection sensitivity and specificity of the GenomEra assay for direct analysis of S. pneumoniae in signal positive blood culture bottles was 100%, respectively. With a straightforward sample preparation protocol of blood cultures the results were available within 55 min, thus being significantly quicker than by the routinely used identification methods (18-48 h). The two-step, time-resolved fluorometric measurement mode employed by the GenomEra CDX(TM) instrument showed no interference from blood or charcoal. CONCLUSION: The GenomEra S. pneumoniae assay is a tool that performs well for the rapid and reliable detection of S. pneumoniae in blood cultures. PMID- 26162004 TI - Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced? AB - In this monograph, we ask whether various kinds of intellectual, physical, and social activities produce cognitive enrichment effects-that is, whether they improve cognitive performance at different points of the adult life span, with a particular emphasis on old age. We begin with a theoretical framework that emphasizes the potential of behavior to influence levels of cognitive functioning. According to this framework, the undeniable presence of age-related decline in cognition does not invalidate the view that behavior can enhance cognitive functioning. Instead, the course of normal aging shapes a zone of possible functioning, which reflects person-specific endowments and age-related constraints. Individuals influence whether they function in the higher or lower ranges of this zone by engaging in or refraining from beneficial intellectual, physical, and social activities. From this point of view, the potential for positive change, or plasticity, is maintained in adult cognition. It is an argument that is supported by newer research in neuroscience showing neural plasticity in various aspects of central nervous system functioning, neurochemistry, and architecture. This view of human potential contrasts with static conceptions of cognition in old age, according to which decline in abilities is fixed and individuals cannot slow its course. Furthermore, any understanding of cognition as it occurs in everyday life must make a distinction between basic cognitive mechanisms and skills (such as working-memory capacity) and the functional use of cognition to achieve goals in specific situations. In practice, knowledge and expertise are critical for effective functioning, and the available evidence suggests that older adults effectively employ specific knowledge and expertise and can gain new knowledge when it is required. We conclude that, on balance, the available evidence favors the hypothesis that maintaining an intellectually engaged and physically active lifestyle promotes successful cognitive aging. First, cognitive-training studies have demonstrated that older adults can improve cognitive functioning when provided with intensive training in strategies that promote thinking and remembering. The early training literature suggested little transfer of function from specifically trained skills to new cognitive tasks; learning was highly specific to the cognitive processes targeted by training. Recently, however, a new generation of studies suggests that providing structured experience in situations demanding executive coordination of skills-such as complex video games, task-switching paradigms, and divided attention tasks-train strategic control over cognition that does show transfer to different task environments. These studies suggest that there is considerable reserve potential in older adults' cognition that can be enhanced through training. Second, a considerable number of studies indicate that maintaining a lifestyle that is intellectually stimulating predicts better maintenance of cognitive skills and is associated with a reduced risk of developing Alzheimer's disease in late life. Our review focuses on longitudinal evidence of a connection between an active lifestyle and enhanced cognition, because such evidence admits fewer rival explanations of observed effects (or lack of effects) than does cross-sectional evidence. The longitudinal evidence consistently shows that engaging in intellectually stimulating activities is associated with better cognitive functioning at later points in time. Other studies show that meaningful social engagement is also predictive of better maintenance of cognitive functioning in old age. These longitudinal findings are also open to important rival explanations, but overall, the available evidence suggests that activities can postpone decline, attenuate decline, or provide prosthetic benefit in the face of normative cognitive decline, while at the same time indicating that late-life cognitive changes can result in curtailment of activities. Given the complexity of the dynamic reciprocal relationships between stimulating activities and cognitive function in old age, additional research will be needed to address the extent to which observed effects validate a causal influence of an intellectually engaged lifestyle on cognition. Nevertheless, the hypothesis that an active lifestyle that requires cognitive effort has long-term benefits for older adults' cognition is at least consistent with the available data. Furthermore, new intervention research that involves multimodal interventions focusing on goal-directed action requiring cognition (such as reading to children) and social interaction will help to address whether an active lifestyle enhances cognitive function. Third, there is a parallel literature suggesting that physical activity, and aerobic exercise in particular, enhances older adults' cognitive function. Unlike the literature on an active lifestyle, there is already an impressive array of work with humans and animal populations showing that exercise interventions have substantial benefits for cognitive function, particularly for aspects of fluid intelligence and executive function. Recent neuroscience research on this topic indicates that exercise has substantial effects on brain morphology and function, representing a plausible brain substrate for the observed effects of aerobic exercise and other activities on cognition. Our review identifies a number of areas where additional research is needed to address critical questions. For example, there is considerable epidemiological evidence that stress and chronic psychological distress are negatively associated with changes in cognition. In contrast, less is known about how positive attributes, such as self-efficacy, a sense of control, and a sense of meaning in life, might contribute to preservation of cognitive function in old age. It is well known that certain personality characteristics such as conscientiousness predict adherence to an exercise regimen, but we do not know whether these attributes are also relevant to predicting maintenance of cognitive function or effective compensation for cognitive decline when it occurs. Likewise, more information is needed on the factors that encourage maintenance of an active lifestyle in old age in the face of elevated risk for physiological decline, mechanical wear and tear on the body, and incidence of diseases with disabling consequences, and whether efforts to maintain an active lifestyle are associated with successful aging, both in terms of cognitive function and psychological and emotional well-being. We also discuss briefly some interesting issues for society and public policy regarding cognitive-enrichment effects. For example, should efforts to enhance cognitive function be included as part of a general prevention model for enhancing health and vitality in old age? We also comment on the recent trend of business marketing interventions claimed to build brain power and prevent age-related cognitive decline, and the desirability of direct research evidence to back claims of effectiveness for specific products. PMID- 26162003 TI - NUCB2/nesfatin-1 Is Associated with Elevated Levels of Anxiety in Anorexia Nervosa. AB - OBJECTIVE: NUCB2/nesfatin-1 is an anorexigenic hormone with elevated levels in obese and decreased levels in anorexia nervosa (AN) patients. Moreover, a role in the regulation of stress and emotions was suggested by several rodent and preliminary human studies. Since anxiety and depression are common comorbidities in AN, we investigated the association of NUCB2/nesfatin-1 with anxiety, depression and perceived stress in AN. METHODS: We analyzed circulating NUCB2/nesfatin-1 levels in 64 female inpatients diagnosed with anorexia nervosa (body mass index, BMI; mean+/-SD, 14.7+/-2.3 kg/m2). At the same time anxiety (GAD-7), depression (PHQ-9), stress (PSQ-20) and disordered eating (EDI-2) were measured psychometrically. RESULTS: No correlation was observed between NUCB2/nesfatin-1 and BMI (r = 0.06, p = 0.70). The study population was divided in patients with low anxiety (n = 32, GAD-7 scores, mean+/-SD, 7.5+/-3.3) and high anxiety (n = 32, 16.0+/-3.0, p<0.001). Patients with high anxiety scores displayed 65% higher NUCB2/nesfatin-1 levels (p = 0.04). This was reflected by a positive correlation of GAD-7 and NUCB2/nesfatin-1-levels (r = 0.32, p = 0.04). Scores of PSQ-20 (73.3+/-14.3 vs. 48.6+/-17.2) and PHQ-9 (18.8+/-5.0 vs. 10.3+/ 5.1) were higher in the high anxiety group (p<0.001) but did not correlate with NUCB2/nesfatin-1 (p>0.05). EDI-2 total score was also higher in the high anxiety group (52.3+/-14.1 vs. 40.2+/-16.0, p = 0.02), while no correlations of EDI-2 scores with plasma NUCB2/nesfatin-1 were observed (p>0.05). CONCLUSIONS: Circulating NUCB2/nesfatin-1 levels correlated positively with perceived anxiety, whereas no association with BMI or eating disorder symptoms was observed. NUCB2/nesfatin-1 might be primarily involved in the modulation of anxiety and subsequently in the regulation of eating habits and body weight in AN. PMID- 26162005 TI - Prospects for Improving Cognition Throughout the Life Course. PMID- 26162007 TI - Evolution of magnetism on a curved nano-surface. AB - To design custom magnetic nanostructures, it is indispensable to acquire precise knowledge about the systems in the nanoscale range where the magnetism forms. In this paper we present the effect of a curved surface on the evolution of magnetism in ultrathin iron films. Nominally 70 A thick iron films were deposited in 9 steps on 3 different types of templates: (a) a monolayer of silica spheres with 25 nm diameter, (b) a monolayer of silica spheres with 400 nm diameter and (c) for comparison a flat silicon substrate. In situ iron evaporation took place in an ultrahigh vacuum chamber using the molecular beam epitaxy technique. After the evaporation steps, time differential nuclear forward scattering spectra, grazing incidence small angle X-ray scattering images and X-ray reflectivity curves were recorded. In order to reconstruct and visualize the magnetic moment configuration in the iron cap formed on top of the silica spheres, micromagnetic simulations were performed for all iron thicknesses. We found a great influence of the template topography on the onset of magnetism and on the developed magnetic nanostructure. We observed an individual magnetic behaviour for the 400 nm spheres which was modelled by vortex formation and a collective magnetic structure for the 25 nm spheres where magnetic domains spread over several particles. Depth selective nuclear forward scattering measurements showed that the formation of magnetism begins at the top region of the 400 nm spheres in contrast to the 25 nm particles where the magnetism first appears in the region where the spheres are in contact with each other. PMID- 26162006 TI - Exome Sequencing Identifies a Missense Variant in EFEMP1 Co-Segregating in a Family with Autosomal Dominant Primary Open-Angle Glaucoma. AB - Primary open-angle glaucoma (POAG) is a clinically important and genetically heterogeneous cause of progressive vision loss as a result of retinal ganglion cell death. Here we have utilized trio-based, whole-exome sequencing to identify the genetic defect underlying an autosomal dominant form of adult-onset POAG segregating in an African-American family. Exome sequencing identified a novel missense variant (c.418C>T, p.Arg140Trp) in exon-5 of the gene coding for epidermal growth factor (EGF) containing fibulin-like extracellular matrix protein 1 (EFEMP1) that co-segregated with disease in the family. Linkage and haplotype analyses with microsatellite markers indicated that the disease interval overlapped a known POAG locus (GLC1H) on chromosome 2p. The p.Arg140Trp substitution was predicted in silico to have damaging effects on protein function and transient expression studies in cultured cells revealed that the Trp140 mutant protein exhibited increased intracellular accumulation compared with wild type EFEMP1. In situ hybridization of the mouse eye with oligonucleotide probes detected the highest levels of EFEMP1 transcripts in the ciliary body, cornea, inner nuclear layer of the retina, and the optic nerve head. The recent finding that a common variant near EFEMP1 was associated with optic nerve-head morphology supports the possibility that the EFEMP1 variant identified in this POAG family may be pathogenic. PMID- 26162009 TI - Isoform-Level Gene Expression Profiles of Human Y Chromosome Azoospermia Factor Genes and Their X Chromosome Paralogs in the Testicular Tissue of Non-Obstructive Azoospermia Patients. AB - The human Y chromosome has an inevitable role in male fertility because it contains many genes critical for spermatogenesis and the development of the male gonads. Any genetic variation or epigenetic modification affecting the expression pattern of Y chromosome genes may thus lead to male infertility. In this study, we performed isoform-level gene expression profiling of Y chromosome genes within the azoospermia factor (AZF) regions, their X chromosome counterparts, and few autosomal paralogues in testicular biopsies of 12 men with preserved spermatogenesis and 68 men with nonobstructive azoospermia (NOA) (40 Sertoli-cell only syndrome (SCOS) and 28 premiotic maturation arrest (MA)). This was undertaken using quantitative real-time PCR (qPCR) at the transcript level and Western blotting (WB) and immunohistochemistry (IHC) at the protein level. We profiled the expression of 41 alternative transcripts encoded by 14 AZFa, AZFb, and AZFc region genes (USP9Y, DDX3Y, XKRY, HSFY1, CYORF15A, CYORF15B, KDM5D, EIF1AY, RPS4Y2, RBMY1A1, PRY, BPY2, DAZ1, and CDY1) as well as their X chromosome homologue transcripts and a few autosomal homologues. Of the 41 transcripts, 18 were significantly down-regulated in men with NOA when compared with those of men with complete spermatogenesis. In contrast, the expression of five transcripts increased significantly in NOA patients. Furthermore, to confirm the qPCR results at the protein level, we performed immunoblotting and IHC experiments (based on 24 commercial and homemade antibodies) that detected 10 AZF-encoded proteins. In addition, their localization in testis cell types and organelles was determined. Interestingly, the two missing proteins, XKRY and CYORF15A, were detected for the first time. Finally, we focused on the expression patterns of the significantly altered genes in 12 MA patients with successful sperm retrieval compared to those of 12 MA patients with failed sperm retrieval to predict the success of sperm retrieval in azoospermic men. We showed that HSFY1-1, HSFY1-3, BPY2-1, KDM5C2, RBMX2, and DAZL1 transcripts could be used as potential molecular markers to predict the presence of spermatozoa in MA patients. In this study, we have identified isoform level signature that can be used to discriminate effectively between MA, SCOS, and normal testicular tissues and suggests the possibility of diagnosing the presence of mature sperm cell in azoospermic men to prevent additional testicular sperm extraction (TESE) surgery. PMID- 26162008 TI - Synthesis and Evaluation of 64Cu-DOTA-NT-Cy5.5 as a Dual-Modality PET/Fluorescence Probe to Image Neurotensin Receptor-Positive Tumor. AB - Overexpression of neurotensin receptors (NTRs) has been suggested to play important roles in the growth and survival of a variety of tumor types. The aim of this study is to develop a dual-modality probe (64Cu -DOTA-NT-Cy5.5) for imaging NTR1 expression in vivo with both positron emission tomography (PET) and fluorescence. In this approach, the thiol group and N terminal amino group of neurotensin analogue (Cys-NT) were chemically modified with Cy5.5 dye and DOTA chelator, respectively. After radiolabeling with 64Cu, the resulting probe (64Cu DOTA-NT-Cy5.5) was evaluated in NTR1 positive HT-29 tumor model. Small animal PET quantification analysis demonstrated that the tumor uptake was 1.91+/-0.22 and 1.79+/-0.16%ID/g at 1 and 4 h postinjection (p.i.), respectively. The tumor-to muscle ratio was 17.44+/-3.25 at 4 h p.i. based on biodistribution. Receptor specificity was confirmed by the successful blocking experiment at 4 h p.i. (0.42+/-0.05%ID/g). In parallel with PET experiment, fluorescence imaging was also performed, which demonstrated prominent tumor uptake in HT-29 model. As a proof of concept, an imaging guided surgery was performed to the fluorescent moiety of this probe and could provide potential surgery guidance for NTR positive patients. In summary, our results clearly indicated that the dual modality probe, 64Cu-DOTA-NT-Cy5.5, could serve as a promising agent to image NTR positive tumors in vivo. PMID- 26162010 TI - Unraveling Pathways of Guaiacol Nitration in Atmospheric Waters: Nitrite, A Source of Reactive Nitronium Ion in the Atmosphere. AB - The tropospheric aqueous-phase aging of guaiacol (2-methoxyphenol, GUA), a lignocellulosic biomass burning pollutant, is addressed in this work. Pathways of GUA nitration in aqueous solution under atmospherically relevant conditions are proposed and critically discussed. The influence of NaNO2 and H2O2, hydroxyl radical scavenger, and sunlight was assessed by an experimental-modeling approach. In the presence of the urban pollutant, nitrite, GUA is preferentially nitrated to yield 4- and 6-nitroguaiacol. After a short lag-time, 4,6 dinitroguaiacol is also formed. Its production accelerates after guaiacol is completely consumed, which is nicely described by the model function accounting for NO2(*) and NO2(+) as nitrating agents. Although the estimated second-order kinetic rate constants of methoxyphenol nitration with NO2(*) are substantially higher than the corresponding rate constants of nitration with NO2(+), nitration rates are competitive under nighttime and liquid atmospheric aerosol-like conditions. In contrast to concentrations of radicals, which are governed by the interplay between diffusion-controlled reactions and are therefore mostly constant, concentrations of electrophiles are very much dependent on the ratio of NO2(-) to activated aromatics in solution. These results contribute substantially to the understanding of methoxyphenol aging in the atmospheric waters and underscore the importance of including electrophilic aromatic substitution reactions in atmospheric models. PMID- 26162011 TI - Development of Robust and Recoverable Ultralow-Fouling Coatings Based on Poly(carboxybetaine) Ester Analogue. AB - Polyurethane with zwitterionic side chains (PCB-ester-PU) based on a poly(carboxybetaine) ester analogue is developed for marine coatings and biomedical applications by introducing dihydroxy-terminated PCB-ester(OH)2 with different polymerization as the macrodiol, 4,4'-diphenylmethane diisocyanate (MDI) as the diisocyanate, and 1,4-butanediol (1,4-BD) as the chain extender. Robust coatings are obtained and exhibit long-term excellent resistance to nonspecific protein adsorption, bacterial adhesion, and human umbilical vein endothelial cell (HUVEC) attachment after hydrolysis. Tests of adhesion on different substrates and film hardness indicate that the material possesses far more stable mechanic properties than hydrogel coatings. Moreover, such a resistance can be generated not only by alkaline solution, but also by a physiological buffer (such as phosphate-buffered saline (0.15 M pH 7.4 PBS)) or by steam in an autoclave. Ultimately, its excellent long-term nonfouling property, its healing capability through self-regeneration and superior mechanic properties (such as hardness and elasticity), and its good adhesiveness as a paint on both polar and nonpolar substrates make this material an ideal candidate as a coating for marine and medical devices. PMID- 26162012 TI - Dashboard report on performance on select quality indicators to cancer care providers. AB - OBJECTIVE: Cancer quality registers are attracting increasing attention as important, but still underutilized sources of clinical data. To optimize the use of registers in quality assurance and improvement, data have to be rapidly collected, collated and presented as actionable, at-a-glance information to the reporting departments. This article presents a dashboard performance report on select quality indicators to cancer care providers. MATERIALS AND METHODS: Ten quality indicators registered on an individual patient level in the National Prostate Cancer Register of Sweden and recommended by the National Prostate Cancer Guidelines were selected. Data reported to the National Prostate Cancer Register are uploaded within 24 h to the Information Network for Cancer Care platform. Launched in 2014, "What''s Going On, Prostate Cancer" provides rapid, at-a-glance performance feedback to care providers. RESULTS: The indicators include time to report to the National Prostate Cancer Register, waiting times, designated clinical nurse specialist, multidisciplinary conference, adherence to guidelines for diagnostic work-up and treatment, and documentation and outcome of treatment. For each indicator, three performance levels were defined. CONCLUSION: What's Going On, a dashboard performance report on 10 selected quality indicators to cancer care providers, provides an example of how data in cancer quality registers can be transformed into condensed, at-a-glance information to be used as actionable metrics for quality assurance and improvement. PMID- 26162013 TI - Inconsistent Range Shifts within Species Highlight Idiosyncratic Responses to Climate Warming. AB - Climate in part determines species' distributions, and species' distributions are shifting in response to climate change. Strong correlations between the magnitude of temperature changes and the extent of range shifts point to warming temperatures as the single most influential factor causing shifts in species' distributions species. However, other abiotic and biotic factors may alter or even reverse these patterns. The importance of temperature relative to these other factors can be evaluated by examining range shifts of the same species in different geographic areas. When the same species experience warming in different geographic areas, the extent to which they show range shifts that are similar in direction and magnitude is a measure of temperature's importance. We analyzed published studies to identify species that have documented range shifts in separate areas. For 273 species of plants, birds, mammals, and marine invertebrates with range shifts measured in multiple geographic areas, 42-50% show inconsistency in the direction of their range shifts, despite experiencing similar warming trends. Inconsistency of within-species range shifts highlights how biotic interactions and local, non-thermal abiotic conditions may often supersede the direct physiological effects of temperature. Assemblages show consistent responses to climate change, but this predictability does not appear to extend to species considered individually. PMID- 26162017 TI - Relative Contributions of Spectral and Temporal Cues to Korean Phoneme Recognition. AB - This study was aimed to evaluate the relative contributions of spectral and temporal information to Korean phoneme recognition and to compare them with those to English phoneme recognition. Eleven normal-hearing Korean-speaking listeners participated in the study. Korean phonemes, including 18 consonants in a /Ca/ format and 17 vowels in a /hVd/ format, were processed through a noise vocoder. The spectral information was controlled by varying the number of channels (1, 2, 3, 4, 6, 8, 12, and 16) whereas the temporal information was controlled by varying the lowpass cutoff frequency of the envelope extractor (1 to 512 Hz in octave steps). A total of 80 vocoder conditions (8 numbers of channels * 10 lowpass cutoff frequencies) were presented to listeners for phoneme recognition. While vowel recognition depended on the spectral cues predominantly, a tradeoff between the spectral and temporal information was evident for consonant recognition. The overall consonant recognition was dramatically lower than that of English consonant recognition under similar vocoder conditions. The complexity of the Korean consonant repertoire, the three-way distinction of stops in particular, hinders recognition of vocoder-processed phonemes. PMID- 26162018 TI - Application of Subspace Clustering in DNA Sequence Analysis. AB - Identification and clustering of orthologous genes plays an important role in developing evolutionary models such as validating convergent and divergent phylogeny and predicting functional proteins in newly sequenced species of unverified nucleotide protein mappings. Here, we introduce an application of subspace clustering as applied to orthologous gene sequences and discuss the initial results. The working hypothesis is based upon the concept that genetic changes between nucleotide sequences coding for proteins among selected species and groups may lie within a union of subspaces for clusters of the orthologous groups. Estimates for the subspace dimensions were computed for a small population sample. A series of experiments was performed to cluster randomly selected sequences. The experimental design allows for both false positives and false negatives, and estimates for the statistical significance are provided. The clustering results are consistent with the main hypothesis. A simple random mutation binary tree model is used to simulate speciation events that show the interdependence of the subspace rank versus time and mutation rates. The simple mutation model is found to be largely consistent with the observed subspace clustering singular value results. Our study indicates that the subspace clustering method may be applied in orthology analysis. PMID- 26162019 TI - Alkylfluorenyl substituted N-heterocyclic carbenes in copper(I) catalysed hydrosilylation of aldehydes and ketones. AB - Copper(i) complexes featuring N-heterocyclic carbenes (NHCs) in which the nitrogen atoms are substituted by a 9-ethyl-9-fluorenyl group (EF) have been synthesised and tested in the hydrosylilation of functionalized and/or sterically demanding ketones and aldehydes. These reactions, carried out with triethylsilane as hydride source, were best achieved with the imidazolylidene copper complex in which the EF substituents can freely rotate about the corresponding N-CEF bonds. The remarkable stability of the active species, which surpasses that of previously reported Cu-NHC catalysts is likely to rely on the ability of the NHC side arms to protect the copper centre during the catalytic cycle by forming sandwich-like intermediates, but also on its steric flexibility facilitating approach of encumbered substrates. TONs up to 1000 were reached. PMID- 26162024 TI - Etoposide-loaded nanostructured lipid carriers for gastric cancer therapy. AB - PURPOSE: Gastric carcinoma is one of the most common cancers and the second most frequent cause of cancer-related deaths. The aim of this study was to prepare and characterize etoposide-loaded nanostructured lipid carriers (ETP-NLCs) and evaluate their antitumor activity in vitro and in vivo. METHODS: Novel ETP-NLCs were constructed. The physicochemical properties of the ETP-NLCs were investigated by particle-size analysis, zeta potential measurement, drug loading, drug entrapment efficiency, stability and in vitro drug release behavior. In vitro cytotoxicity against human gastric cancer cells (SGC7901 cells) was investigated, and in vivo antitumor of NLCs was evaluated on mice bearing SGC7901 cells xenografts. RESULTS: ETP-NLCs have a narrow size distribution at 91 nm, a zeta potential value of +23.1 mV, high drug entrapment efficiency of 78%. The drug release of ETP-NLCs exhibited a sustained behavior, which made it an ideal vehicle for drug delivery. Furthermore, ETP-NLCs could significantly enhance in vitro cytotoxicity and in vivo antitumor effect against SGC7901 cells and gastric cancer animal model compared to the free drug. CONCLUSION: The results demonstrated that the NLCs might be a promising nanomedicine for the treatment of gastric carcinoma. PMID- 26162025 TI - Do Chondral Lesions of the Knee Correlate with Bone Tracer Uptake by Using SPECT/CT? AB - PURPOSE: To evaluate the correlation of bone tracer uptake as determined with single photon emission computed tomography (SPECT)/computed tomography (CT) and the size and severity of chondral lesions detected with magnetic resonance (MR) imaging of the knee. MATERIALS AND METHODS: MR imaging and SPECT/CT images of 63 knee joints in 63 patients (mean age +/- standard deviation, 49.2 years +/- 12.7) with chondral or osteochondral lesions were prospectively collected and retrospectively analyzed after approval by the ethics committee. Chondral lesions were graded on MR images by using a modified Noyes grading scale (grade 0, intact; grade 1, fibrillations; grade 2, <50% defect; grade 3, >50% defect; and grade 4, grade three plus subchondral changes) and measured in two dimensions. Technetium 99m hydroxymethane diphosphonate SPECT/CT bone tracer uptake was volumetrically quantified by using validated software. Maximum values of each subchondral area (patellofemoral or medial and lateral femorotibial) were quantified, and a ratio was calculated in relation to a reference region in the femoral shaft, which represented the bone tracer uptake background activity. Grades and sizes of chondral lesions and bone tracer uptake were correlated by using an independent t test and analysis of variance (P < .05). RESULTS: Bone tracer uptake was low (mean relative uptake, 1.64 +/- 0.95) in knees without any present chondral lesion. In knees with grade 3 and 4 chondral lesions, the relative ratio was significantly higher (3.62 +/- 2.18, P = .002) than in knees with grade 1 and 2 lesions (2.95 +/- 2.07). The larger the diameter of the chondral lesion, the higher the bone tracer uptake. Higher grades of chondral lesions (grades 3 and 4) larger than 4 cm(2) (4.96 +/- 2.43) showed a significantly higher bone tracer uptake than smaller lesions (<1 cm(2), 2.72 +/- 1.43 [P = .011]; and 1-4 cm(2), 3.28 +/- 2.15 [P = .004]). CONCLUSION: SPECT/CT findings significantly correlate with the degree and size of chondral lesions on MR images. Grade 3 and 4 chondral lesions of the knee, as well as larger lesions, correlate with a high bone tracer uptake. PMID- 26162026 TI - Hepatic MR Elastography: Clinical Performance in a Series of 1377 Consecutive Examinations. AB - PURPOSE: To assess the technical success rate and diagnostic performance of liver magnetic resonance (MR) elastography. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board with patient informed consent. A total of 1377 consecutive MR elastography examinations performed between 2007 and 2010 in 1287 patients for clinical indications were included. Medical records were used to retrieve liver stiffness as assessed with MR elastography, histologic analysis, blood work, and other liver disease-related information. Nonparametric Kruskal-Wallis tests and analysis of covariance methods were used to evaluate the diagnostic values and relationships of the collected data. RESULTS: Hepatic MR elastography had a success rate of 94.4% (1300 of 1377 cases) and yielded reproducible measurements (r = 0.9716, P < .0001) in the study cohort, with a complex patient profile and multiple interpreters. Body mass index had no significant effect on success rate (P = .2). In 289 patients who underwent liver biopsy within 1 year of the MR elastography date, mean liver stiffness as assessed with MR elastography was significantly higher in patients with advanced fibrosis (stages F3, F4) than in those with mild to moderate fibrosis (stages F0, F1, F2) (5.93 kPa +/- 2.31 [standard deviation] vs 3.35 kPa +/- 1.44, P < .0001). Liver stiffness is associated with many factors other than fibrosis extent, including cause of fibrosis (viral hepatitis C vs nonalcoholic fatty liver disease, P = .025), inflammation (severe vs mild to moderate, P = .03), and hepatic metabolic and synthetic function (no fibrosis vs intermediate fibrosis, P <= .01). CONCLUSION: In a general clinical practice environment, hepatic MR elastography is a robust imaging method with a high success rate in a broad spectrum of patients. It also shows the complex association between liver stiffness and hepatic pathophysiology. PMID- 26162027 TI - Small Musculoskeletal Soft-Tissue Lesions: US-guided Core Needle Biopsy- Comparative Study of Diagnostic Yields according to Lesion Size. AB - PURPOSE: To determine the effectiveness of ultrasonographically (US) guided core needle biopsy (CNB) for diagnosis of small musculoskeletal soft-tissue lesions by demonstrating the noninferiority of the diagnostic yield with US-guided CNB in lesions measuring 2 cm or smaller to that for lesions larger than 2 cm. MATERIALS AND METHODS: This retrospective study was institutional review board approved, and the requirement to obtain informed consent was waived. Five hundred US-guided CNBs performed for diagnosis of musculoskeletal soft-tissue lesions were included. Results of US-guided CNBs were divided into four categories, and the diagnostic yields were calculated on the basis of lesion size. A one-sided 97.5% confidence interval was calculated to determine the mean difference in diagnostic yields to test for noninferiority. In addition, the diagnostic yield with US guided CNBs for lesions 1 cm or smaller was compared with that for lesions larger than 1 cm. RESULTS: A total of 500 technically successful US-guided CNBs in 494 patients with musculoskeletal soft-tissue lesions who underwent subsequent surgical excision or at least 6 months of follow-up were included. The diagnostic yields with US-guided CNB were 87% for lesions larger than 2 cm and 88% for lesions 2 cm or smaller. The lower bound of the confidence interval was -0.07, thus the noninferiority of the diagnostic yield with CNB for lesions 2 cm or smaller to that for lesions larger than 2 cm was shown. On the other hand, the diagnostic yield with US-guided CNB for lesions 1 cm or smaller was inferior to that for lesions larger than 1 cm. CONCLUSION: US-guided CNB of musculoskeletal soft-tissue lesions is effective for diagnosis and decision making, even in lesions measuring 2 cm or smaller. However, when a lesion is 1 cm or smaller, US guided CNB is more frequently insufficient for histopathologic diagnosis. PMID- 26162028 TI - Phenols displaying tyrosinase inhibition from Humulus lupulus. AB - Tyrosinase is the rate-limiting enzyme for the production of melanin and other pigments via the oxidation of l-tyrosine. The methanol extract from Humulus lupulus showed potent inhibition against mushroom tyrosinase. The bioactivity guided fractionation of this methanol extract resulted in the isolation of seven flavonoids (1-7), identified as xanthohumol (1), 4'-O-methylxanthohumol (2), xanthohumol C (3), flavokawain C (4), xanthoumol B (5), 6-prenylnaringenin (6) and isoxanthohumol (7). All isolated flavonoids (1-7) effectively inhibited the monophenolase (IC50s = 15.4-58.4 uM) and diphenolase (IC50s = 27.1-117.4 uM) activities of tyrosinase. Kinetic studies using Lineweaver-Burk and Dixon-plots revealed that chalcones (1-5) were competitive inhibitors, whereas flavanones (6 and 7) exhibited both mixed and non-competitive inhibitory characteristics. In conclusion, this study is the first to demonstrate that the phenolic phytochemicals of H. lupulus display potent inhibitory activities against tyrosinase. PMID- 26162029 TI - Synthesis, antitumor and antimicrobial activity of some new 6-methyl-3-phenyl 4(3H)-quinazolinone analogues: in silico studies. AB - Some new derivatives of substituted-4(3H)-quinazolinones were synthesized and evaluated for their in vitro antitumor and antimicrobial activities. The results of this study demonstrated that compound 5 yielded selective activities toward NSC Lung Cancer EKVX cell line, Colon Cancer HCT-15 cell line and Breast Cancer MDA-MB-231/ATCC cell line, while NSC Lung Cancer EKVX cell line and CNS Cancer SF 295 cell line were sensitive to compound 8. Additionally, compounds 12 and 13 showed moderate effectiveness toward numerous cell lines belonging to different tumor subpanels. On the other hand, the results of antimicrobial screening revealed that compounds 1, 9 and 14 are the most active against Staphylococcus aureus ATCC 29213 with minimum inhibitory concentration (MIC) of 16, 32 and 32 MUg/mL respectively, while compound 14 possessed antimicrobial activities against all tested strains with the lowest MIC compared with other tested compounds. In silico study, ADME-Tox prediction and molecular docking methodology were used to study the antitumor activity and to identify the structural features required for antitumor activity. PMID- 26162030 TI - Common Cell Shape Evolution of Two Nasopharyngeal Pathogens. AB - Respiratory infectious diseases are the third cause of worldwide death. The nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as Neisseria meningitidis and Moraxella catarrhalis. These microbes possess several surface structures that interact with the actors of the innate immune system. In our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences in cell wall structure, one of the strongest immune-modulators. We were able to show that a modification of peptidoglycan (PG) composition (increased proportion of pentapeptides) and a cell shape change from rod to cocci had been selected for along the past evolution of N. meningitidis. Using genomic comparison across species, we correlated the emergence of the new cell shape (cocci) with the deletion, from the genome of N. meningitidis ancestor, of only one gene: yacF. Moreover, the reconstruction of this genetic deletion in a bacterium harboring the ancestral version of the locus together with the analysis of the PG structure, suggest that this gene is coordinating the transition from cell elongation to cell division. Accompanying the loss of yacF, the elongation machinery was also lost by several of the descendants leading to the change in the PG structure observed in N. meningitidis. Finally, the same evolution was observed for the ancestor of M. catarrhalis. This suggests a strong selection of these genetic events during the colonization of the nasopharynx. This selection may have been forced by the requirement of evolving permissive interaction with the immune system, the need to reduce the cellular surface exposed to immune attacks without reducing the intracellular storage capacity, or the necessity to better compete for adhesion to target cells. PMID- 26162031 TI - Neuroophthalmological outcomes associated with use of the Pipeline Embolization Device: analysis of the PUFS trial results. AB - OBJECT: Neuroophthalmological morbidity is commonly associated with large and giant cavernous and supraclinoid internal carotid artery (ICA) aneurysms. The authors sought to evaluate the neuroophthalmological outcomes after treatment of these aneurysms with the Pipeline Embolization Device (PED). METHODS: The Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial was an international, multicenter prospective trial evaluating the safety and efficacy of the PED. All patients underwent complete neuroophthalmological examinations both before the PED procedure and at a 6-month follow-up. All examinations were performed for the purpose of this study and according to study criteria. RESULTS: In total, 108 patients were treated in the PUFS trial, 98 of whom had complete neuroophthalmological follow-up. Of the patients with complete follow-up, 39 (40%) presented with a neuroophthalmological baseline deficit that was presumed to be attributable to the aneurysm, and patients with these baseline deficits had significantly larger aneurysms. In 25 of these patients (64%), the baseline deficit showed at least some improvement 6 months after PED treatment, whereas in 1 patient (2.6%), the deficits only worsened. In 5 patients (5%), new deficits had developed at the 6-month follow-up, while in another 6 patients (6%), deficits that were not originally assumed to be related to the aneurysm had improved by that time. A history of diabetes was associated with failure of the baseline deficits to improve after the treatment. The aneurysm maximum diameter was significantly larger in patients with a new deficit or a worse baseline deficit at 6 months postprocedure. CONCLUSIONS: Patients treated with the PED for large and giant ICA aneurysms had excellent neuroophthalmological outcomes 6 months after the procedure, with deficits improving in most of the patients, very few deficits worsening, and few new deficits developing. PMID- 26162032 TI - Outcomes of chronic subdural hematoma drainage in nonagenarians and centenarians: a multicenter study. AB - OBJECTIVE: Chronic subdural hemorrhage (SDH) or hematoma is a condition that affects elderly individuals. With advances in medical care, the number of nonagenarians and centenarians will increase. However, surgical treatments in this age group are associated with high rates of morbidity and mortality. Because no data are available on the rates of survival among elderly patients with chronic SDHs who undergo surgical drainage or receive only conservative care, the goal of this study was to determine survival rates in patients 90 years of age or older with symptomatic chronic SDHs. METHODS: The authors conducted a retrospective analysis of patient data that were collected at 3 hospitals over a 13-year period (from January 2001 to June 2013). The data from patients 90 years or older with symptomatic chronic SDHs and who were offered surgical treatment were included in the analysis. Patients who underwent surgical treatment were included in the surgical group and patients who declined an operation were included in the conservative care group. The patients' Charlson Comorbidity Index score, Karnofsky Performance Scale score, dates of death, presenting symptoms, Glasgow Coma Scale score, length of stay in the hospital, discharge location, side of the SDH, and neurological improvements at 30-day and 6-month follow-ups were recorded. Data were statistically analyzed with Fisher exact test, Kaplan Meier curves, and logistic regression. RESULTS: In total, 101 patients met the inclusion criteria of this study; 70 of these patients underwent surgical drainage, and 31 received conservative care. Patients in the surgical group had statistically significantly (p < 0.001) higher survival at both the 30-day and 6 month follow-ups, with 92.9% and 81.4% of the patients in this group surviving for at least 30 days and 6 months, respectively, versus 58.1% and 41.9%, respectively, in the conservative care group. Moreover, the mean overall length of survival of 34.4 +/- 28.7 months was longer in the surgical group than it was in the conservative care group (11.3 +/- 16.6 months). Overall, 95.7% of patients in the surgical group exhibited an improvement in neurological status after the SDH drainage, whereas none of the patients in the conservative care group showed any neurological improvement during their hospital stay. The surgical complication rate was 11.4%, and the overall rate of chronic SDH recurrence after surgery was 12.9%. CONCLUSIONS: Surgical drainage of chronic SDHs in nonagenarians and centenarians is associated with lower incidence of inpatient death and higher 30-day and 6-month survival rates. PMID- 26162033 TI - Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women. AB - OBJECT The incidence of subarachnoid hemorrhage (SAH) increases after menopause. Anecdotal data suggest that hormone replacement therapy (HRT) may reduce the rate of SAH and aneurysm formation in women. The goal of this study was to determine the effect of HRT on occurrence of SAH in a large prospective cohort of postmenopausal women. METHODS The data were analyzed for 93, 676 women 50-79 years of age who were enrolled in the observational arm of the Women's Health Initiative Study. The effect of HRT on risk of SAH was determined over a period of 12 +/- 1 years (mean +/- SD) using Cox proportional hazards analysis after adjusting for potential confounders. Additional analysis was performed to identify the risk associated with "estrogen only" and "estrogen and progesterone" HRT among women. RESULTS Of the 93, 676 participants, 114 (0.1%) developed SAH during the follow-up period. The rate of SAH was higher among women on active HRT compared with those without HRT used (0.14% vs 0.11%, absolute difference 0.03%, p < 0.0001). In unadjusted analysis, participants who reported active use of HRT were 60% more likely to suffer an SAH (RR 1.6, 95% CI 1.1-2.3). Compared with women without HRT use, the risk of SAH continued to be higher among women reporting active use of HRT (RR 1.5, 95% CI 1.0-2.2) after adjusting for age, systolic blood pressure, cigarette smoking, alcohol consumption, body mass index, race/ethnicity, diabetes, and cardiovascular disease. The risk of SAH was nonsignificantly higher among women on "estrogen only" HRT (RR 1.4, 95% CI 0.91 2.0) than "estrogen and progesterone" HRT(RR 1.2, 95% CI 0.8-2.1) after adjusting for the above-mentioned confounders. CONCLUSIONS Postmenopausal women, particularly those at risk for SAH due to presence of unruptured aneurysms, family history, or cardiovascular risk factors, should be counseled against use of HRT. PMID- 26162034 TI - Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study. AB - OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study. PMID- 26162036 TI - Acute progression of untreated incidental WHO Grade II glioma to glioblastoma in an asymptomatic patient. AB - WHO Grade II glioma (low-grade glioma [LGG]) is increasingly diagnosed as an incidental finding in patients undergoing MRI for many conditions. Recent data have demonstrated that such incidental LGGs are progressive tumors that undergo clinical transformation and ultimately become malignant. Although asymptomatic LGG seems to represent an earlier step in the natural course of a glioma than the symptomatic LGG, it is nonetheless impossible to predict at the individual level when the tumor will become malignant. The authors report the case of a 43-year old woman with a right operculo-insular LGG that was incidentally diagnosed because of headaches. No treatment was proposed, and repeated MRI scans were performed for 6 years in another institution. Due to a slow but continuous growth of the lesion, the patient was finally referred to our center to undergo surgery. Interestingly, objective calculation of the velocity of the tumor's diametric expansion demonstrated a sudden acceleration of the growth rate within the 5 months preceding surgery, with the development of contrast enhancement. Remarkably, the patient was still asymptomatic. An awake resection was performed with intraoperative electrical mapping. There was no functional worsening following surgery, as assessed on postoperative neuropsychological examination. Removal of 92% of signal abnormality on FLAIR MRI was achieved, with complete resection of the area of contrast enhancement. Neuropathological examination revealed a glioblastoma, and the patient was subsequently treated with concomitant radiotherapy and chemotherapy. Although a "wait and see" attitude has been advocated by some authors with respect to incidental LGG, our original case demonstrates that acute transformation to glioblastoma may nonetheless occur, even before the onset of any symptoms. Therefore, because the lack of symptoms does not protect from malignant transformation, we propose consideration of earlier resection in a more systematic manner in cases of incidental LGG. PMID- 26162035 TI - Use of optical coherence tomography to predict visual outcome in parachiasmal meningioma. AB - OBJECT: The authors investigated the value of retinal nerve fiber layer (RNFL) thickness in predicting visual outcome after surgery for parachiasmal meningioma. METHODS: Forty-nine eyes of 25 patients who underwent craniotomy and resection of a parachiasmal meningioma were analyzed retrospectively. Visual parameters including visual field (VF) (recorded as the mean deviation [MD]), visual acuity (VA), and RNFL thickness (via optical coherence tomography) were measured before and 1 week, 6 months, and 1 year after surgery. Postoperative visual outcome was compared among the patients with a thin or normal RNFL. A separate analysis of data pertaining to 22 eyes of 13 patients with severe VF defects (MD <= -10 dB) was performed to compare visual outcome for those with a thin or normal RNFL. RESULTS: Of the 23 eyes that showed VF improvement, 22 (95.7%) had normal RNFL thickness. The positive predictive value of normal RNFL thickness for VF improvement was 78.6%. The VF of patients with normal RNFL thickness improved in 6 months and continued improving 1 year after surgery (MD -5.9 dB before surgery, -5.5 dB 1 week after surgery, -2.8 dB 6 months after surgery [p < 0.01], and -1.1 dB 1 year after surgery [p < 0.01]). In contrast, those with a thin preoperative RNFL showed deterioration at first and then slower, worse visual recovery after surgery (MD -18.1 dB before surgery, -22.4 dB 1 week after surgery, -21.2 dB 6 months after surgery, and -19.1 dB 1 year after surgery). VA also showed significant progress 6 months after surgery in patients with normal RNFL thickness (0.6 before surgery, 0.7 one week after surgery, 0.9 six months after surgery [p = 0.025], and 0.9 one year after surgery [p = 0.050]) compared to those with a thin RNFL (0.3 before surgery, 0.2 one week after surgery, 0.3 six months after surgery, and 0.4 one year after surgery). Preoperative differences in VF MD and VA were noted between the 2 groups (p < 0.01). Even patients with severe VF defects and normal RNFL thickness improved by 11.1 dB by 1 year after surgery compared with patients with a thin RNFL (-0.01 dB) (p < 0.01). Patients with normal RNFL thickness also did better in VA improvement (from 0.7 to 1.1) than those with a thin RNFL (from 0.2 to 0.3), but these results were not statistically significant. CONCLUSIONS: RNFL thickness measured by optical coherence tomography has significant value as a prognostic factor of postoperative visual recovery for parachiasmal meningioma. Patients with normal RNFL thickness before surgery are more likely to have visual improvement after surgery than patients with a thin RNFL. PMID- 26162037 TI - Reduction in high-frequency hearing loss following technical modifications to microvascular decompression for hemifacial spasm. AB - OBJECT: Microvascular decompression is a safe and effective procedure to treat hemifacial spasm, but the operation poses some risk to the patient's hearing. While severe sensorineural hearing loss across all frequencies occurs at a low rate in experienced hands, a recent study suggests that as many as one-half of patients who undergo this procedure may experience ipsilateral high-frequency hearing loss (HFHL), and as many as one-quarter may experience contralateral HFHL. While it has been suggested that drill-related noise may account for this finding, this study was designed to examine the effect of a number of techniques designed to protect the vestibulocochlear nerve from operative manipulation on the incidence of HFHL. METHODS: Pure-tone audiometry was performed both preoperatively and postoperatively on 67 patients who underwent microvascular decompression for hemifacial spasm during the study period. A change of greater than 10 dB at either 4 kHz or 8 kHz was considered to be HFHL. Additionally, the authors analyzed intraoperative brainstem auditory evoked potentials from this patient cohort. RESULTS: The incidence of ipsilateral HFHL in this cohort was 7.4%, while the incidence of contralateral HFHL was 4.5%. One patient (1.5%; also included in the HFHL group) experienced an ipsilateral nonserviceable hearing loss. CONCLUSIONS: The reduced incidence of HFHL in this study suggests that technical modifications including performing the procedure without the use of fixed retraction may greatly reduce, but not eliminate, the occurrence of HFHL following microvascular decompression for hemifacial spasm. PMID- 26162038 TI - Editorial: Is volume a proxy for quality? PMID- 26162039 TI - Quantitative tumor volumetric responses after Gamma Knife radiosurgery for meningiomas. AB - OBJECT The reported tumor control rates for meningiomas after stereotactic radiosurgery (SRS) are high; however, early imaging assessment of tumor volumes may not accurately predict the eventual tumor response. The objective in this study was to quantitatively evaluate the volumetric responses of meningiomas after SRS and to determine whether early volume responses are predictive of longer-term tumor control. METHODS The authors performed a retrospective review of 252 patients (median age 56 years, range 14-87 years) who underwent Gamma Knife radiosurgery between 2002 and 2010. All patients had evaluable pre- and postoperative T1-weighted contrast-enhanced MRIs. The median baseline tumor volume was 3.5 cm(3) (range 0.2-33.8 cm(3)) and the median follow-up was 19.5 months (range 0.1-104.6 months). Follow-up tumor volumes were compared with baseline volumes. Tumor volume percent change and the tumor volume rate of change were compared at 3-month intervals. Eventual tumor responses were classified as progressed for > 15% volume change, regressed for <= 15% change, and stable for +/- 15% of baseline volume at time of last follow-up. Volumetric data were compared with the final tumor status by using univariable and multivariable logistic regression. RESULTS Tumor volume regression (median decrease of -40.2%) was demonstrated in 168 (67%) patients, tumor stabilization (median change of 2.7%) in 67 (26%) patients, and delayed tumor progression (median increase of 104%) in 17 (7%) patients (p < 0.001). Tumors that eventually regressed had an average volume reduction of -18.2% at 3 months. Tumors that eventually progressed all demonstrated volume increase by 6 months. Transient progression was observed in 15 tumors before eventual decrease, and transient regression was noted in 6 tumors before eventual volume increase. CONCLUSIONS The volume response of meningiomas after SRS is dynamic, and early imaging estimations of the tumor volume may not correlate with the final tumor response. However, tumors that ultimately regressed tended to respond in the first 3 months, whereas tumors that ultimately progressed showed progression within 6 months. PMID- 26162040 TI - Hospital volume and 1-year mortality after treatment of intracranial aneurysms: a study based on patient registries in Scandinavia. AB - OBJECT: The object of this study was to examine the relationship between hospital volume and long-term mortality after treatment of intracranial aneurysms. METHODS: The authors identified patients treated for intracranial aneurysms between 2002 and 2010 from patient registries of Denmark, Norway, and Sweden, and linked to data on 1-year mortality from the population registry of each country. Cox regression models were used to relate hospital volume to the risk of death and adjusted for potential confounders (age, sex, year of treatment, Charlson comorbidity index, country, and surgical treatment). RESULTS: The authors identified 5773 patients with ruptured and 1756 patients with unruptured intracranial aneurysms, treated at 15 hospitals. One-year mortality rates were 15.6% for patients with ruptured aneurysms and 2.7% for patients with unruptured aneurysms. No consistent relationship was found between hospital volume and 1 year mortality for ruptured aneurysms in the unadjusted analyses, but higher hospital volume was associated with increased mortality in the analyses adjusted for potential confounders (hazard ratio [HR] per 10-patient increase 1.04, 95% CI 1.00-1.07). There was a trend toward a lower mortality rate in higher-volume hospitals after treatment for unruptured intracranial aneurysms, but this was not statistically significant after adjustment for potential confounders (HR per 10 patient increase 0.69, 95% CI 0.42-1.10). There were large variations in mortality after treatment for both ruptured and unruptured intracranial aneurysms across hospitals and between the Scandinavian countries (p < 0.01). CONCLUSIONS: The findings in this study did not confirm a relationship between higher hospital volume and reduced long-term mortality after treatment of ruptured intracranial aneurysms. Prospective registries for evaluating outcomes after aneurysm treatment are highly warranted. PMID- 26162041 TI - Genetic characterization of skull base chondrosarcomas. AB - OBJECT: Although chondrosarcomas rarely arise in the skull base, chondrosarcomas and chordomas are the 2 major malignant bone neoplasms occurring at this location. The distinction of these 2 tumors is important, but this distinction is occasionally problematic because of radiological and histological overlap. Unlike chordoma and extracranial chondrosarcoma, no case series presenting a whole genome analysis of skull base chondrosarcomas (SBCSs) has been reported. The goal of this study is to clarify the genetic characteristics of SBCSs and contrast them with those of chordomas. METHODS: The authors analyzed 7 SBCS specimens for chromosomal copy number alterations (CNAs) using comparative genomic hybridization (CGH). They also examined IDH1 and IDH2 mutations and brachyury expression. RESULTS: In CGH analyses, the authors detected CNAs in 6 of the 7 cases, including chromosomal gains of 8q21.1, 19, 2q22-q32, 5qcen-q14, 8q21-q22, and 15qcen-q14. Mutation of IDH1 was found with a high frequency (5 of 7 cases, 71.4%), of which R132S was most frequently mutated. No IDH2 mutations were found, and immunohistochemical staining for brachyury was negative in all cases. CONCLUSIONS: To the best of the authors' knowledge, this is the first whole genome study of an SBSC case series. Their findings suggest that these tumors are molecularly consistent with a subset of conventional central chondrosarcomas and different from skull base chordomas. PMID- 26162042 TI - Hormone-dependent shrinkage of a sphenoid wing meningioma after pregnancy: case report. AB - Meningiomas are known to be associated with female sex hormones. Worsening neurological symptoms or newly diagnosed meningiomas have been described in the context of elevated levels of sex hormones, for example, in pregnancy. To the authors' knowledge, tumor shrinkage after the normalization of hormones has not been described, even if it is known that neurological deficits due to meningioma compression may improve after giving birth. A 32-year-old female patient presented with severe headache and vision disturbances at the end of her second pregnancy. Magnetic resonance imaging revealed an extended mass at the lateral left-sided sphenoid wing that was suspected to be a meningioma. After delivery, the patient's symptoms improved, and MRI obtained 2 months postpartum showed significant shrinkage of the lesion. Significant tumor shrinkage can occur after pregnancy. Thus, repeat imaging is indicated in these patients. PMID- 26162043 TI - Application of a 980-nanometer diode laser in neuroendoscopy: a case series. AB - OBJECTIVE: Ventricular neuroendoscopy represents an important advance in the treatment of hydrocephalus. High-power (surgical) Nd:YAG laser and low-level laser therapy (using 685-nm-wavelength diode laser) have been used in conjunction with neuroendoscopy with favorable results. This study evaluated the use of surgical 980-nm-wavelength diode laser for the neuroendoscopic treatment of ventricular diseases. METHODS: Nine patients underwent a neuroendoscopic procedure with 980-nm diode laser. Complications and follow-up were recorded. RESULTS: Three in-hospital postoperative complications were recorded (1 intraventricular hemorrhage and 2 meningitis cases). The remaining 6 patients had symptom improvement after endoscopic surgery and were discharged from the hospital within 24-48 hours after surgery. Patients were followed for an average of 14 months: 1 patient developed meningitis and another died suddenly at home. The other patients did well and were asymptomatic until the last follow-up consultation. CONCLUSIONS: The 980-nm diode laser is considered an important therapeutic tool for endoscopic neurological surgeries. This study showed its application in different ventricular diseases. PMID- 26162044 TI - Letter to the Editor: Gamma Knife radiosurgery for vestibular schwannoma. PMID- 26162045 TI - Letter to the Editor: Save the nerve. PMID- 26162046 TI - Gamma Knife radiosurgery for recurrent or residual seizures after anterior temporal lobectomy in mesial temporal lobe epilepsy patients with hippocampal sclerosis: long-term follow-up results of more than 4 years. AB - OBJECT: Gamma Knife radiosurgery (GKRS) has proven efficacy in the treatment of drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and is comparable to conventional resective surgery. It may be effective as an alternative treatment to reoperation after failed temporal lobe surgery in patients with MTLE-HS. The purpose of this study was to investigate the efficacy of GKRS in patients with unilateral MTLE-HS who did not achieve seizure control or had recurrent seizures after anterior temporal lobectomy (ATL). METHODS: Twelve patients (8 males; mean age 35.50 +/- 9.90 years) with MTLE-HS who underwent GKRS after failed ATL (Engel Classes III-IV) were included. GKRS targets included the remnant tissue or adjacent regions of the previously performed ATL with a marginal dose of 24-25 Gy at the 50% isodose line in all patients. Final seizure outcome was assessed using Engel's modified criteria during the final 2 years preceding data analysis. A comparison between signal changes on follow-up MRI and clinical outcome was performed. RESULTS: All patients were followed up for at least 4 years with a mean duration of 6.18 +/- 1.77 years (range 4-8.8 years) after GKRS. At the final assessment, 6 of 12 patients were classified as seizure free (Engel Class Ia, n = 3; Ic, n = 2; and Id, n = 1) and 6 patients were classified as not seizure free (Engel Class II, n = 1; III, n = 2; and IV, n = 3). Neither initial nor late MRI signal changes after GKRS statistically correlated with surgical outcome. Clinical seizure outcome did not differ significantly with initial or late MRI changes after GKRS. CONCLUSIONS: GKRS can be considered an alternative option when the patients with MTLE-HS who had recurrent or residual seizures after ATL refuse a second operation. PMID- 26162047 TI - Timing of deep vein thrombosis formation after aneurysmal subarachnoid hemorrhage. AB - OBJECT: Deep vein thrombosis (DVT) is a common complication of aneurysmal subarachnoid hemorrhage (aSAH). The time period of greatest risk for developing DVT after aSAH is not currently known. aSAH induces a prothrombotic state, which may contribute to DVT formation. Using repeated ultrasound screening, the hypothesis that patients would be at greatest risk for developing DVT in the subacute post-rupture period was tested. METHODS: One hundred ninety-eight patients with aSAH admitted to the Oregon Health & Science University Neurosciences Intensive Care Unit between April 2008 and March 2012 were included in a retrospective analysis. Ultrasound screening was performed every 5.2 +/- 3.3 days between admission and discharge. The chi-square test was used to compare DVT incidence during different time periods of interest. Patient baseline characteristics as well as stroke severity and hospital complications were evaluated in univariate and multivariate analyses. RESULTS: Forty-two (21%) of 198 patients were diagnosed with DVT, and 3 (2%) of 198 patients were symptomatic. Twenty-nine (69%) of the 42 cases of DVT were first detected between Days 3 and 14, compared with 3 cases (7%) detected between Days 0 and 3 and 10 cases (24%) detected after Day 14 (p < 0.05). The postrupture 5-day window of highest risk for DVT development was between Days 5 and 9 (40%, p < 0.05). In the multivariate analysis, length of hospital stay and use of mechanical prophylaxis alone were significantly associated with DVT formation. CONCLUSIONS: DVT formation most commonly occurs in the first 2 weeks following aSAH, with detection in this cohort peaking between Days 5 and 9. Chemoprophylaxis is associated with a significantly lower incidence of DVT. PMID- 26162048 TI - Complete mitochondrial genome of the Scorpaenopsis cirrhosa (Scorpaeniformes: Scorpaenidae). AB - The complete mitochondrial genome of the Scorpaenopsis cirrhosa has been sequenced. The mitochondrial genome is 16 966 bp in length, containing 13 protein coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1 control region. The gene order and composition of S. cirrhosa mitochondrial genome was similar to that of most other vertebrates. The overall nucleotides base composition of the heavy strand is A (27.91%), G (17.71%), C (28.02%), and T (26.35%). With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. The tRNA-Ser2 gene lacked DHC arm and could not fold into a typical clover-leaf secondary structure. Seen from the phylogenetic tree, S. cirrhosa, a stonefish and four rockfishes from the same order (Scorpaeniformes) clustered into one branch. PMID- 26162049 TI - Mitochondrial genome sequence of Paramisgurnus dabryanus from the Yellow River estuary: implication for Cobitidae phylogeny. AB - Paramisgurnus dabryanus Sauvage (Cobitidae, Cypriniformes) is a native large scale loach widely distributed in main inland freshwater systems of China. The complete mitochondrial genome sequence of P. dabryanus from the Yellow River (YR) estuary was characterized in the present study. The circular mitogenome is 16 570 bp in size and contains two ribosomal RNA genes, 22 transfer RNA genes, and 13 protein-coding genes. The overall A + T content is 56.64% in the range of other Cobitidae studied. The mitogenome of P. dabryanus YR has an overall nucleotide sequence identity of 96.9% with that from Zhejiang, and 89.2% with that from Hubei. All the Misgurnus and Paramisgurnus species were clustered into two Misgurnus/Paramisgurnus complex clades with high bootstrap values based on the whole mitogenome sequences. The mitochondrial phylogenomic analysis indicates that the relationships in Cobitidae are inconsistent with the current classification system and taxonomic revision is required on the basis of molecular phylogeny and morphology. PMID- 26162050 TI - Genetic relationship and population structure of three Indian local chicken populations as revealed by mtDNA D-loop. AB - The genetic information obtained from the mitochondrial DNA D-loop region has paramount importance in understanding the evolution of closely related individuals, and designing proper breeding or conservation plans. The present study was conducted using partial D-loop sequences of three local poultry populations from Odisha, India. The partial D-loop sequences were found to be highly polymorphic having 164 polymorphic sites with 89 singletons and 75 parsimony informative sites. Furthermore, 25 insertion and deletion sites were observed. High genetic diversity was observed within three local chicken populations. Highest genetic difference was observed between Gujuri and Kalua population (0.2230) followed by Gujuri and Hansli (0.199) and Kalua with Hansli (0.166). The pairwise mismatch distribution showed that all populations are of constant size over time. Phylogenetic tree analysis indicated that the said three populations were close to the referred population of China, Sri Lanka, Indonesia and Japan than Aseel and Kadaknath (Indian native breeds). PMID- 26162051 TI - The complete chloroplast genome sequence of Panax quinquefolius (L.). AB - The complete chloroplast genome sequence of Panax quinquefolius, an important medicinal herb, was generated by de novo assembly with low-coverage whole-genome sequence data and manual correction. A circular 156 088-bp chloroplast genome showed typical chloroplast genome structure comprising a large single copy region of 86 095 bp, a small single copy region of 17 993 bp, and a pair of inverted repeats of 26 000 bp. The chloroplast genome had 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis with the chloroplast genome revealed that P. quinquefolius is much closer to P. ginseng than P. notoginseng. PMID- 26162052 TI - Complete mitochondrial genome of Callithrix kuhlii (Primates: Callitrichinae) with phylogenetic consideration. AB - The Wied's black-tufted-ear marmoset, Callithrix kuhlii, is a New World monkey that lives in tropical and subtropical forests of eastern Brazil. In this study, the mitochondrial genome sequence of this species is determined, which is found to be 16 500 bp in length and consists of 22 transfer RNA genes, 13 protein coding genes, 2 ribosomal RNA genes and one D-loop control region. The overall nucleotide composition is 32.73% of A, 26.80% of T, 27.04% of C and 13.43% of G, with an AT content of 59.53%. The genome structure about gene order and composition of C. kuhlii mitochondrial genome is similar to those of most other vertebrates. With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all the other genes are encoded on the heavy strand. Phylogenetic analysis shows that C. kuhlii and C. jacchus are more closely related to each other than to other marmosets of the genus Callithrix that have its mitochondrial genome published. PMID- 26162053 TI - The complete mitochondrial genome of Spotted Munia Lonchura punctulata topela (Passeriformes: Estrildidae). AB - Spotted Munia Lonchura punctulata is a sparrow-sized estrildid finch native to tropical Asia. In this study, we used PCR-based method to determine the complete mitochondrial genome of Lonchura punctulata topela. The mitochondrial genome of Spotted Munia is a 16 824-bp circular molecule, which contains 37 typical mitochondrial genes (13 protein-coding genes, two rRNAs, and 22 tRNAs) and a 1247 bp A + T- rich region. The gene arrangement pattern is identical to Taeniopygia guttata and Passer montanus. All the start codons of PCGs are typical ATG, except for the COI and ND3 genes. TAN is the most frequent stop codon, and TAN and T- are also found very common. The non-coding region contains some inter-genic spacers and a control region. The phylogenetic trees from the Bayesian and neighbor-joining analyses, based on the complete mtDNA of 12 Passeriformes species, share similar topologies and high node support values. Lonchura punctulata topela has close relative with Taeniopygia guttata. PMID- 26162054 TI - Complete mitochondrial genomes of Teinopalpus imperialis (Lepidoptera: Papilionidae) and phylogenetic relationships analyses. AB - In this study, we sequenced the complete mitochondrial genome of Teinopalpus imperialis, which is a national butterfly of India, and a grade-II protected species in China. The complete mtDNA from T. imperialis was 15 299 base pairs in length and contained 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and 401 bp non-coding region. The T. imperialis genes were highly similar to those of sequenced mitogenomes of other lepidopteran species in the order and orientation. Twelve PCGs (ND2, ATP8, ND3, COII, ATP6, COIII, ND4, ND4L, CytB, ND1, ND5, and ND6) start with a typical ATN codon, only the COI gene starts with CGA codon. Eight PCGs (ND2, COI, ATP8, ATP6, COIII, ND5, ND6, and Cyt B) terminate in the common stop codon TAA, three PCGs (ND4L, ND3, and ND1) terminate in the stop codon TAG, and two PCGs (COII and ND4) terminate in a single T residue. The phylogenetic relationships were reconstructed with the concatenated sequences of the 13 PCGs of the mitochondrial genome, and phylogenetic results showed that Danaidae, Satyridae, Libytheidae, Nymphalidae, Acraeidae, Pieridae, Hesperiidae, Riodinidae, and Lycaenidae are monophyletic clades. PMID- 26162055 TI - Complete mitochondrial genome of the golden-crowned sifaka, Propithecus tattersalli (Primates: Indriidae). AB - The golden-crowned sifaka, Propithecus tattersalli, is a critically endangered social lemur species that inhabits the restricted and highly fragmented semi evergreen forests. In this study, we determined the complete mitochondrial genome sequence of this species for the first time. The results shows that this mtDNA genome is 17 099 bp in size, and comprises 22 transfer RNA genes, 13 protein coding genes, two ribosomal RNA genes, and one control region (D-loop). The overall base composition in descending order is A (32.91%), C (27.07%), T (27.04%), and G (12.98%), so the percentage of A and T (59.95%) is slightly higher than that of G and C. The gene order and the composition of P. tattersalli mitochondrial genome are exactly similar to those of most other vertebrates. All the genes are encoded on the heavy strand with the exception of NADH dehydrogenase subunit six (ND6) and eight tRNA genes. Phylogenetic analysis suggests that the P. tattersalli exhibits most close relationship with P. coquereli. The complete mitochondrial genome sequence presented here will be useful for further phylogenetic analysis and conservation genetic studies in P. tattersalli. PMID- 26162056 TI - New Anthocyanin-Human Salivary Protein Complexes. AB - The interaction between phenolic compounds and salivary proteins is considered the basis of the poorly understood phenomenon of astringency. Furthermore, this interaction is an important factor in relation to their bioavailability. In this work, interactions between anthocyanin and human salivary protein fraction were studied by mass spectrometry (MALDI-TOF-MS and FIA-ESI-MS) and saturation transfer difference (STD) NMR spectroscopy. Anthocyanins were able to interact with saliva proteins. The dissociation constant (KD) between malvidin 3-glucoside and salivary proline-rich proteins was 1.92 mM for the hemiketal form (pH 3.4) and 1.83 mM for the flavylium cation (pH 1.0). New soluble complexes between these salivary proteins and malvidin 3-glucoside were identified for the first time. PMID- 26162058 TI - Letter From the Incoming Editor. PMID- 26162057 TI - Does Nursing Home Ownership Change Affect Family Ratings on Experience with Care? AB - Person-centeredness may suffer in nursing homes (NHs) with recent ownership changes. This study identifies associations between ownership change and reported care experiences, important measures of person-centered care for long-term residents in Maryland NHs. Care experience measures and ownership change data were collected from Maryland Health Care Commission reports, which reported data on 220 Maryland NHs from 2011 and 2012. Facility and market covariates were obtained from 2011 NH Compare and Area Health Resource Files. Linear regression was used to examine whether ownership change in 2011 was associated with lower care experience ratings reported during April to June 2012. Dependent variables were overall care rating (scale 1-10), percentage of respondents answering that they would recommend the NH, and assessments of five care and resident life domains (scale 1-4). Care experiences reported in 2012 were high; however, after controlling for covariates, ownership change was associated with significant decreases in 6 out of 7 measures, including a 0.39-point decrease in overall care rating (p = .001). NH managers and policy makers should consider strategies to improve patient-centeredness after ownership change. PMID- 26162059 TI - The Psychology of Residential Mobility: Implications for the Self, Social Relationships, and Well-Being. AB - Residential mobility is an increasingly important personal and societal issue in both the United States and the world in general. However, it has received relatively limited attention in psychological theorizing and research. This article demonstrates the importance of residential mobility in understanding the self, social relationships, and well-being. Recent research has shown that residential mobility (number of moves for an individual or percentage having moved recently for a neighborhood) is associated with the primacy of the personal over the collective self. It is also associated with "duty-free" friendships and group memberships rather than obligatory friendships and group memberships. Overall, residential mobility is associated with lower levels of well-being at the individual level of analysis. Finally, residential mobility is associated with personal forms of subjective well-being (based on self-esteem, the verification of the personal self) as opposed to interpersonal forms of subjective well-being (based on social support, the verification of the collective selves). In short, residential mobility is a powerful, parsimonious explanatory construct in the self, social relationships, and subjective well being and may be a key to understanding the future of mind and behavior in the increasingly mobile world. PMID- 26162060 TI - Why Humans Are Unique: Three Theories. AB - Three recent papers reject Darwin's claim that there is no fundamental difference between humans and animals. Each offers a unique theory of the difference. The first theory holds that although animals can perceive perceptual relations, humans alone can reinterpret the higher order relations between these relations. The theory offers analogical reasoning as an example of the uniquely human ability to deal with higher order relations between relations. However, chimpanzees are capable of analogical reasoning if the analogies are conceptually simple. The second theory proposes that human intelligence has far better developed social than physical competence-a claim that ignores, and is contradicted by 20 years of infant research showing that the infant's social and physical modules are almost equally developed. The third theory finds that whereas animal abilities are limited adaptations restricted to a single goal, human abilities are domain general and serve indeterminately many goals. This article rejects the first two theories and explains the unique character of domain-general human competence in terms of the interweaving of evolutionarily independent abilities-an interweaving found in humans only. PMID- 26162061 TI - Trading Spaces: Carving Up Events for Learning Language. AB - Relational terms (e.g., verbs and prepositions) are the cornerstone of language development, bringing together two distinct fields: linguistic theory and infants' event processing. To acquire relational terms such as run, walk, in, and on, infants must first perceive and conceptualize components of dynamic events such as containment-support, path-manner, source-goal, and figure-ground. Infants must then uncover how the particular language they are learning encodes these constructs. This review addresses the interaction of language learning with infants' conceptualization of these nonlinguistic spatial event components. We present the thesis that infants start with language-general nonlinguistic constructs that are gradually refined and tuned to the requirements of their native language. In effect, infants are trading spaces, maintaining their sensitivity to some relational distinctions while dampening other distinctions, depending on how their native language expresses these constructs. PMID- 26162062 TI - Directed Attention as a Common Resource for Executive Functioning and Self Regulation. AB - Research on executive functioning and on self-regulation have each identified a critical resource that is central to that domain and is susceptible to depletion. In addition, studies have shown that self-regulation tasks and executive functioning tasks interact with each other, suggesting that they may share resources. Other research has focused specifically on restoring what we propose is the shared resource between self-regulation and executive functioning. Utilizing a theory-based natural environment intervention, these studies have found improvements in executive-functioning performance and self-regulation effectiveness, suggesting that the natural environment intervention restores this shared resource. PMID- 26162063 TI - Rethinking "Generation Me": A Study of Cohort Effects From 1976-2006. AB - Social commentators have argued that changes over the last decades have coalesced to create a relatively unique generation of young people. However, using large samples of U.S. high-school seniors from 1976 to 2006 (Total N = 477,380), we found little evidence of meaningful change in egotism, self-enhancement, individualism, self-esteem, locus of control, hopelessness, happiness, life satisfaction, loneliness, antisocial behavior, time spent working or watching television, political activity, the importance of religion, and the importance of social status over the last 30 years. Today's youth are less fearful of social problems than previous generations and they are also more cynical and less trusting. In addition, today's youth have higher educational expectations than previous generations. However, an inspection of effect sizes provided little evidence for strong or widespread cohort-linked changes. PMID- 26162064 TI - Commentary on Trzesniewski and Donnellan (2010): A Transdisciplinary Perspective on Young People's Well-Being. AB - The health and well-being of young people are important not only for their own sake, but also for the future health of populations and societies. Yet the debate about the patterns and trends in young people's well-being and their causes is marked by uncertainty and contradiction. This article draws on evidence from trend analyses, cross-sectional studies, research on explanatory factors, expert opinion, and public-attitude surveys to argue that social changes of the last half century have harmed successive generations of young people because of their developmental vulnerability and that these young people have carried their enhanced risk into later life. PMID- 26162065 TI - Birth Cohort Differences in the Monitoring the Future Dataset and Elsewhere: Further Evidence for Generation Me-Commentary on Trzesniewski & Donnellan (2010). AB - A substantial majority of published studies have reported increases of individualism and materialism and declines in mental health and interpersonal trust over generations. The data Trzesniewski and Donnellan (2010, this issue) present from the Monitoring the Future (MTF) survey of high-school students is almost entirely consistent with these previous findings, showing decreases in civic interest and trust and increases in high expectations, materialism, and self-satisfaction. Problems with measurement and variable labeling explain the few seeming discrepancies. They analyze only 15% of the variables in MTF, ignoring many others that also demonstrate increases in individualistic traits. Ecological correlations are not an issue in previous studies as the individual level standard deviation is used to compute effect sizes. Increases in narcissism are clear when important moderator variables (e.g., campus) are controlled. The real puzzle is why these authors' conclusions fall so far from the data. PMID- 26162066 TI - Oh, Grow Up! Generational Grumbling and the New Life Stage of Emerging Adulthood Commentary on Trzesniewski & Donnellan (2010). AB - In this commentary on the article by Trzesniewski and Donnellan (2010, this issue), I focus on the question of why young people today are viewed so negatively, despite the lack of evidence that they are worse (or worse off) now than they were in decades past. I propose that an important reason is the rise of emerging adulthood as a new life stage in between adolescence and young adulthood. Emerging adulthood developed in part because young people enter adult roles of stable work, marriage, and parenthood later now than they did in the past, leading many older people to view them as "late" or selfish, and the new features of this new life stage are frequently misunderstood and misinterpreted. I emphasize that the rise emerging adulthood is not merely generational but is likely to be a permanent addition to the life course. PMID- 26162067 TI - Secular Trends and Personality: Perspectives From Longitudinal and Cross-Cultural Studies-Commentary on Trzesniewski & Donnellan (2010). AB - According to cross-temporal meta-analyses (Twenge, 2000, 2001), social trends over the last decades have powerfully influenced the personality profiles of children and students, with effects accounting for 20% of the variance of Neuroticism and Extraversion. However, Trzesniewski and Donnellan (2010, this issue), who examined a large and representative U.S. high-school student sample, found little evidence of secular trends. In this commentary, I emphasize the distinction between cohort and period effects and review findings from longitudinal and cross-cultural studies on the role of social trends and other cultural influences on personality traits. Analyses of adult personality scores from the Baltimore Longitudinal Study of Aging provide little support for powerful secular effects on Neuroticism and Extraversion; evidence supports a secular trend of declining trust, along with additional small effects on other facets of personality. Analyses of personality scores from around the world suggest that social and cultural differences account for about 5% of the variance on major dimensions of personality. The integration of findings from multiple perspectives provides useful insights into the role of the environment on personality traits. PMID- 26162068 TI - Groundhog Day Versus Alice in Wonderland, Red Herrings Versus Swedish Fishes, and Hopefully Something Constructive: A Reply to Comments. AB - In this reply to the comments on our original article, we identify common themes and respond to some specific issues that appear to be at the core of the debate over the evidence for "Generation Me." In particular, we point out that generational studies have both applied and theoretical consequences and echo the sentiment that developmental considerations are likely to be more important than generational considerations when thinking about the attributes of today's young people. We also acknowledge that disagreements are inevitable, as this is a controversial issue of study. However, we reiterate our commitment to the interpretation of effect sizes rather than null hypothesis significance testing and emphasize the need for care when psychological scientists offer broad and often moralistic pronouncements about entire generations of young people. PMID- 26162069 TI - Identification of MicroRNAs in Response to Different Day Lengths in Soybean Using High-Throughput Sequencing and qRT-PCR. AB - MicroRNAs (miRNAs) are short, non-coding single-strand RNA molecules that play important roles in plant growth, development and stress responses. Flowering time affects the seed yield and quality of soybean. However, the miRNAs involved in the regulation of flowering time in soybean have not been reported until recently. Here, high-throughput sequencing and qRT-PCR were used to identify miRNAs involved in soybean photoperiodic pathways. The first trifoliate leaves of soybean that receive the signal of light treatment were used to construct six libraries (0, 8, and 16 h under short-day (SD) treatment and 0, 8, and 16 h under long-day (LD) treatment). The libraries were sequenced using Illumina Solexa. A total of 318 known plant miRNAs belonging to 163 miRNA families and 81 novel predicted miRNAs were identified. Among these, 23 miRNAs at 0 h, 65 miRNAs at 8 h and 83 miRNAs at 16 h, including six novel predicted miRNAs at 8 h and six novel predicted miRNAs at 16 h, showed differences in abundance between LD and SD treatments. Furthermore, the results of GO and KEGG analyses indicated that most of the miRNA targets were transcription factors. Seven miRNAs at 0 h, 23 miRNAs (including four novel predicted miRNAs) at 8 h, 16 miRNAs (including one novel predicted miRNA) at 16 h and miRNA targets were selected for qRT-PCR analysis to assess the accuracy of the sequencing and target prediction. The results indicated that the expression patterns of the selected miRNAs and miRNA targets showed no differences between the qRT-PCR and sequencing results. In addition, 23 miRNAs at 0 h, 65 miRNAs at 8 h and 83 miRNAs at 16 h responded to day length changes in soybean, including six novel predicted miRNAs at 8 h and six novel predicted miRNAs at 16 h. These results provided an important molecular basis to understand the regulation of flowering time through photoperiodic pathways in soybean. PMID- 26162070 TI - Direct Estimates of the Genomic Contributions to Blood Pressure Heritability within a Population-Based Cohort (ARIC). AB - Blood pressure (BP) is a heritable trait with multiple environmental and genetic contributions, with current heritability estimates from twin and family studies being ~ 40%. Here, we use genome-wide polymorphism data from the Atherosclerosis Risk in Communities (ARIC) study to estimate BP heritability from genomic relatedness among cohort members. We utilized data on 6,365,596 and 9,578,528 genotyped and imputed common single nucleotide polymorphisms (SNPs), in 8,901 European ancestry (EA) and 2,860 African Ancestry (AA) ARIC participants, respectively, and a mixed linear model for analyses, to make four observations. First, for BP measurements, the heritability is ~20%/~50% and ~27%/~39% for systolic (SBP)/diastolic (DBP) blood pressure in European and African ancestry individuals, respectively, consistent with prior studies. Second, common variants with allele frequency >10% recapitulate most of the BP heritability in these data. Third, the vast majority of BP heritability varies by chromosome, depending on its length, and is largely concentrated in noncoding genomic regions annotated as DNaseI hypersensitive sites (DHSs). Fourth, the majority of this heritability arises from loci not harboring currently known cardiovascular and renal genes. Recent meta-analyses of large-scale genome-wide association studies (GWASs) and admixture mapping have identified ~50 loci associated with BP and hypertension (HTN), and yet they account for only a small fraction (~2%) of the heritability. PMID- 26162071 TI - The Effect of Training on Postural Control in Dyslexic Children. AB - The aim of this study was to explore whether a short postural training period could affect postural stability in dyslexic children. Postural performances were evaluated using Multitest Equilibre from Framiral. Posture was recorded in three different viewing conditions (eyes open fixating a target, eyes closed and eyes open with perturbed vision) and in two different postural conditions (on stable and unstable support). Two groups of dyslexic children participated in the study, i.e. G1: 16 dyslexic participants (mean age 9.9 +/- 0.3 years) who performed short postural training and G2: 16 dyslexic participants of similar ages (mean age 9.1 +/- 0.3 years) who did not perform any short postural training. Findings showed that short postural training improved postural stability on unstable support surfaces with perturbed vision: indeed the surface, the mean velocity of CoP and the spectral power indices in both directions decreased significantly, and the cancelling time in the antero-posterior direction improved significantly. Such improvement could be due to brain plasticity, which allows better performance in sensory process and cerebellar integration. PMID- 26162073 TI - Comparing Methods for Prioritising Protected Areas for Investment: A Case Study Using Madagascar's Dry Forest Reptiles. AB - There are insufficient resources available to manage the world's existing protected area portfolio effectively, so the most important sites should be prioritised in investment decision-making. Sophisticated conservation planning and assessment tools developed to identify locations for new protected areas can provide an evidence base for such prioritisations, yet decision-makers in many countries lack the institutional support and necessary capacity to use the associated software. As such, simple heuristic approaches such as species richness or number of threatened species are generally adopted to inform prioritisation decisions. However, their performance has never been tested. Using the reptile fauna of Madagascar's dry forests as a case study, we evaluate the performance of four site prioritisation protocols used to rank the conservation value of 22 established and candidate protected areas. We compare the results to a benchmark produced by the widely-used systematic conservation planning software Zonation. The four indices scored sites on the basis of: i) species richness; ii) an index based on species' Red List status; iii) irreplaceability (a key metric in systematic conservation planning); and, iv) a novel Conservation Value Index (CVI), which incorporates species-level information on endemism, representation in the protected area system, tolerance of habitat degradation and hunting/collection pressure. Rankings produced by the four protocols were positively correlated to the results of Zonation, particularly amongst high scoring sites, but CVI and Irreplaceability performed better than Species Richness and the Red List Index. Given the technological capacity constraints experienced by decision-makers in the developing world, our findings suggest that heuristic metrics can represent a useful alternative to more sophisticated analyses, especially when they integrate species-specific information related to extinction risk. However, this can require access to, and understanding of, more complex species data. PMID- 26162072 TI - The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS Challenged Mice. AB - The secreted, goblet cell-derived protein Clca1 (chloride channel regulator, calcium-activated-1) has been linked to diseases with mucus overproduction, including asthma and cystic fibrosis. In the intestine Clca1 is found in the mucus with an abundance and expression pattern similar to Muc2, the major structural mucus component. We hypothesized that Clca1 is required for the synthesis, structure or barrier function of intestinal mucus and therefore compared wild type and Clca1-deficient mice under naive and at various time points of DSS (dextran sodium sulfate)-challenged conditions. The mucus phenotype in Clca1-deficient compared to wild type mice was systematically characterized by assessment of the mucus protein composition using proteomics, immunofluorescence and expression analysis of selected mucin genes on mRNA level. Mucus barrier integrity was assessed in-vivo by analysis of bacterial penetration into the mucus and translocation into sentinel organs combined analysis of the fecal microbiota and ex-vivo by assessment of mucus penetrability using beads. All of these assays revealed no relevant differences between wild type and Clca1 deficient mice under steady state or DSS-challenged conditions in mouse colon. Clca1 is not required for mucus synthesis, structure and barrier function in the murine colon. PMID- 26162074 TI - Public Health Responses to Reemergence of Animal Rabies, Taiwan, July 16-December 28, 2013. AB - Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961. In July 2013, rabies was confirmed among three wild ferret-badgers, prompting public health response to prevent human rabies cases. This descriptive study reports the immediate response to the reemergence of rabies in Taiwan. Response included enhanced surveillance for human rabies cases by testing stored cerebrospinal fluids (CSF) from patients with encephalitides of unknown cause by RT-PCR, prioritizing vaccine use for postexposure prophylaxis (PEP) during periods of vaccine shortage and subsequent expansion of PEP, surveillance of animal bites using information obtained from vaccine application, roll out of preexposure prophylaxis (PrEP) with vaccine stock restoration, surveillance for adverse events following immunization (AEFI), and ensuring surge capacity to respond to general public inquiries by phone and training for healthcare professionals. Enhanced surveillance for human rabies found no cases after testing 205 stored CSF specimens collected during January 2010-July 2013. During July 16 to December 28, 2013, we received 8,241 rabies PEP application; 6,634 (80.5%) were consistent with recommendations. Among the 6,501 persons who received at least one dose of rabies vaccine postexposure, 4,953 (76.2%) persons who were bitten by dogs; only 59 (0.9%) persons were bitten by ferret-badgers. During the study period, 6,247 persons received preexposure prophylaxis. There were 23 reports of AEFI; but no anaphylaxis, Guillain-Barre syndrome, or acute disseminated encephalomyelitis were found. During the study period, there were 40,312 calls to the Taiwan Centers for Disease Control hotline, of which, 8,692 (22%) were related to rabies. Recent identification of rabies among ferret-badgers in a previously rabies-free country prompted rapid response. To date, no human rabies has been identified. Continued multifaceted surveillance and interministerial collaboration are crucial to achieve the goal of rabies-free status in Taiwan. PMID- 26162075 TI - Comprehensive Analysis of a Vibrio parahaemolyticus Strain Extracellular Serine Protease VpSP37. AB - Proteases play an important role in the field of tissue dissociation combined with regenerative medicine. During the years new sources of proteolytic enzymes have been studied including proteases from different marine organisms both eukaryotic and prokaryotic. Herein we have purified a secreted component of an isolate of Vibrio parahaemolyticus, with electrophoretic mobilities corresponding to 36 kDa, belonging to the serine proteases family. Sequencing of the N-terminus enabled the in silico identification of the whole primary structure consisting of 345 amino acid residues with a calculated molecular mass of 37.4 KDa. The purified enzyme, named VpSP37, contains a Serine protease domain between residues 35 and 276 and a canonical Trypsin/Chimotrypsin 3D structure. Functional assays were performed to evaluate protease activity of purified enzyme. Additionally the performance of VpSP37 was evaluated in tissue dissociations experiments and the use of such enzyme as a component of enzyme blend for tissue dissociation procedures is strongly recommended. PMID- 26162076 TI - The Quality of the Evidence According to GRADE Is Predominantly Low or Very Low in Oral Health Systematic Reviews. AB - OBJECTIVES: The main objective was to assess the credibility of the evidence using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in oral health systematic reviews on the Cochrane Database of Systematic Reviews (CDSR) and elsewhere. STUDY DESIGN AND SETTING: Systematic Reviews or meta analyses (January 2008-December 2013) from 14 high impact general dental and specialty dental journals and the Cochrane Database of Systematic Reviews were screened for meta-analyses. Data was collected at the systematic review, meta analysis and trial level. Two reviewers applied and agreed on the GRADE rating for the selected meta-analyses. RESULTS: From the 510 systematic reviews initially identified 91 reviews (41 Cochrane and 50 non-Cochrane) were eligible for inclusion. The quality of evidence was high in 2% and moderate in 18% of the included meta-analyses with no difference between Cochrane and non-Cochrane reviews, journal impact factor or year of publication. The most common domains prompting downgrading of the evidence were study limitations (risk of bias) and imprecision (risk of play of chance). CONCLUSION: The quality of the evidence in oral health assessed using GRADE is predominantly low or very low suggesting a pressing need for more randomised clinical trials and other studies of higher quality in order to inform clinical decisions thereby reducing the risk of instituting potentially ineffective and/or harmful therapies. PMID- 26162077 TI - The Role of Amino Acid Permeases and Tryptophan Biosynthesis in Cryptococcus neoformans Survival. AB - Metabolic diversity is an important factor during microbial adaptation to different environments. Among metabolic processes, amino acid biosynthesis has been demonstrated to be relevant for survival for many microbial pathogens, whereas the association between pathogenesis and amino acid uptake and recycling are less well-established. Cryptococcus neoformans is an opportunistic fungal pathogen with many habitats. As a result, it faces frequent metabolic shifts and challenges during its life cycle. Here we studied the C. neoformans tryptophan biosynthetic pathway and found that the pathway is essential. RNAi indicated that interruptions in the biosynthetic pathway render strains inviable. However, auxotroph complementation can be partially achieved by tryptophan uptake when a non preferred nitrogen source and lower growth temperature are applied, suggesting that amino acid permeases may be the target of nitrogen catabolism repression (NCR). We used bioinformatics to search for amino acid permeases in the C. neoformans and found eight potential global permeases (AAP1 to AAP8). The transcriptional profile of them revealed that they are subjected to regulatory mechanisms which are known to respond to nutritional status in other fungi, such as (i) quality of nitrogen (Nitrogen Catabolism Repression, NCR) and carbon sources (Carbon Catabolism Repression, CCR), (ii) amino acid availability in the extracellular environment (SPS-sensing) and (iii) nutritional deprivation (Global Amino Acid Control, GAAC). This study shows that C. neoformans has fewer amino acid permeases than other model yeasts, and that these proteins may be subjected to complex regulatory mechanisms. Our data suggest that the C. neoformans tryptophan biosynthetic pathway is an excellent pharmacological target. Furthermore, inhibitors of this pathway cause Cryptococcus growth arrest in vitro. PMID- 26162078 TI - Transcriptomic-Wide Discovery of Direct and Indirect HuR RNA Targets in Activated CD4+ T Cells. AB - Due to poor correlation between steady state mRNA levels and protein product, purely transcriptomic profiling methods may miss genes posttranscriptionally regulated by RNA binding proteins (RBPs) and microRNAs (miRNAs). RNA immunoprecipitation (RIP) methods developed to identify in vivo targets of RBPs have greatly elucidated those mRNAs which may be regulated via transcript stability and translation. The RBP HuR (ELAVL1) and family members are major stabilizers of mRNA. Many labs have identified HuR mRNA targets; however, many of these analyses have been performed in cell lines and oftentimes are not independent biological replicates. Little is known about how HuR target mRNAs behave in conditional knock-out models. In the present work, we performed HuR RIP Seq and RNA-Seq to investigate HuR direct and indirect targets using a novel conditional knock-out model of HuR genetic ablation during CD4+ T activation and Th2 differentiation. Using independent biological replicates, we generated a high coverage RIP-Seq data set (>160 million reads) that was analyzed using bioinformatics methods specifically designed to find direct mRNA targets in RIP Seq data. Simultaneously, another set of independent biological replicates were sequenced by RNA-Seq (>425 million reads) to identify indirect HuR targets. These direct and indirect targets were combined to determine canonical pathways in CD4+ T cell activation and differentiation for which HuR plays an important role. We show that HuR may regulate genes in multiple canonical pathways involved in T cell activation especially the CD28 family signaling pathway. These data provide insights into potential HuR-regulated genes during T cell activation and immune mechanisms. PMID- 26162079 TI - Obesity as a Potential Risk Factor for Blepharoptosis: The Korea National Health and Nutrition Examination Survey 2008-2010. AB - PURPOSE: To examine obesity parameters as potential risk factors associated with blepharoptosis in a representative Korean population. METHODS: We analyzed the Korea National Health and Nutrition Examination Survey (KNHANES), conducted between 2008 and 2010. 10,285 Korean adults (4,441 men and 5,844 women) aged 40 years or older was enrolled. We compared body mass index (BMI), waist circumference (WC) and percentage body fat (BF), according to the severity of blepharoptosis. Multiple logistic regression analysis was conducted to examine the associations of each obesity parameter with blepharoptosis. RESULTS: The overall prevalence of age-related blepharoptosis was 14.8 % in South Korea. There were significant and graded associations between increasing blepharoptosis severity and the mean value of obesity parameters (P for trend < 0.05). As marginal reflex distance 1 (MRD1) decreased, the prevalence of general obesity and overweight status increased (P for trend=0.121 in men and < 0.001 in women); the prevalence of abdominal obesity increased (P for trend < 0.001 for both genders); the prevalence of highest quartile of percentage BF increased (P for trend <=0.001 for both genders). Blepharoptosis was significantly associated with general obesity in women (adjusted odds ratio (aOR), 2.14; 95% confidence intervals (CI), 1.32-3.47); and with the highest quartile of percentage BF in men (aOR, 2.01; 95% CI, 1.34-2.97) and in women (aOR, 1.52; 95% CI, 1.06-2.3317, after adjusting for age, smoking exercise, drinking alcohol, total energy intake, fat intake, total cholesterol, and high density lipoprotein cholesterol, diabetes, hypertension, and family history of eye disease. CONCLUSIONS: The etiology of age-related blepharoptosis may be multifactorial and is unclear. Our results suggest that obesity parameters such as BMI, WC and percentage BF might be potential risk factors for age-related blepharoptosis in a representative Korean population. PMID- 26162080 TI - Assessing Dissimilarity Measures for Sample-Based Hierarchical Clustering of RNA Sequencing Data Using Plasmode Datasets. AB - Sample- and gene-based hierarchical cluster analyses have been widely adopted as tools for exploring gene expression data in high-throughput experiments. Gene expression values (read counts) generated by RNA sequencing technology (RNA-seq) are discrete variables with special statistical properties, such as over dispersion and right-skewness. Additionally, read counts are subject to technology artifacts as differences in sequencing depth. This possesses a challenge to finding distance measures suitable for hierarchical clustering. Normalization and transformation procedures have been proposed to favor the use of Euclidean and correlation based distances. Additionally, novel model-based dissimilarities that account for RNA-seq data characteristics have also been proposed. Adequacy of dissimilarity measures has been assessed using parametric simulations or exemplar datasets that may limit the scope of the conclusions. Here, we propose the simulation of realistic conditions through creation of plasmode datasets, to assess the adequacy of dissimilarity measures for sample based hierarchical clustering of RNA-seq data. Consistent results were obtained using plasmode datasets based on RNA-seq experiments conducted under widely different conditions. Dissimilarity measures based on Euclidean distance that only considered data normalization or data standardization were not reliable to represent the expected hierarchical structure. Conversely, using either a Poisson based dissimilarity or a rank correlation based dissimilarity or an appropriate data transformation, resulted in dendrograms that resemble the expected hierarchical structure. Plasmode datasets can be generated for a wide range of scenarios upon which dissimilarity measures can be evaluated for sample-based hierarchical clustering analysis. We showed different ways of generating such plasmodes and applied them to the problem of selecting a suitable dissimilarity measure. We report several measures that are satisfactory and the choice of a particular measure may rely on the availability on the software pipeline of preference. PMID- 26162081 TI - Functional Characterization of a Ketoreductase-Encoding Gene med-ORF12 Involved in the Formation of a Stereospecific Pyran Ring during the Biosynthesis of an Antitumor Antibiotic Medermycin. AB - Medermycin, a polyketide antibiotic, possesses strong bioactivity against a variety of tumors through a novel mechanism and is structurally featured with a pyran ring containing two chiral centers (3S and 15R). By far the biosynthetic origin of such enantiomerical conformations still remains obscure. In the present study, we reported the functional characterization of a proposed ketoreductase Med-ORF12 encoded by medermycin biosynthetic cluster and revealed its involvement in the stereochemical control at C3 center of medermycin. Firstly, bioinformatics analysis of Med-ORF12 suggested that it belongs to a group of stereospecific ketoreductases. Next, a Med-ORF12-deficient mutant was obtained and LC/MS measurements demonstrated that medermycin production was completely abolished in this mutant. Meanwhile, it was found that two shunt products were accumulated at the absence of Med-ORF12. Finally, the reintroduction of Med-ORF12 into this mutant could restore the production of medermycin. In a conclusion, these data supported that Med-ORF12 is essential for the biosynthesis of medermycin and performs its role as a stereospecifc ketoreductase in the tailoring steps of medermycin biosynthetic pathway. PMID- 26162082 TI - Microbiological and Chemical Quality of Packaged Sachet Water and Household Stored Drinking Water in Freetown, Sierra Leone. AB - Packaged drinking water (PW) sold in bottles and plastic bags/sachets is widely consumed in low- and middle-income countries (LMICs), and many urban users in sub Saharan Africa (SSA) rely on packaged sachet water (PSW) as their primary source of water for consumption. However, few rigorous studies have investigated PSW quality in SSA, and none have compared PSW to stored household water for consumption (HWC). A clearer understanding of PSW quality in the context of alternative sources is needed to inform policy and regulation. As elsewhere in SSA, PSW is widely consumed in Sierra Leone, but government oversight is nearly nonexistent. This study examined the microbiological and chemical quality of a representative sample of PSW products in Freetown, Sierra Leone at packaged water manufacturing facilities (PWMFs) and at points of sale (POSs). Samples of HWC were also analyzed for comparison. The study did not find evidence of serious chemical contamination among the parameters studied. However, 19% of 45 PSW products sampled at the PWMF contained detectable Escherichia coli (EC), although only two samples exceeded 10 CFU/100 mL. Concentrations of total coliforms (TC) in PSW (but not EC) increased along the supply chain. Samples of HWC from 60 households in Freetown were significantly more likely to contain EC and TC than PSW at the point of production (p<0.01), and had significantly higher concentrations of both bacterial indicators (p<0.01). These results highlight the need for additional PSW regulation and surveillance, while demonstrating the need to prioritize the safety of HWC. At present, PSW may be the least unsafe option for many households. PMID- 26162083 TI - Unique Effects of Acute Aripiprazole Treatment on the Dopamine D2 Receptor Downstream cAMP-PKA and Akt-GSK3beta Signalling Pathways in Rats. AB - Aripiprazole is a wide-used antipsychotic drug with therapeutic effects on both positive and negative symptoms of schizophrenia, and reduced side-effects. Although aripiprazole was developed as a dopamine D2 receptor (D2R) partial agonist, all other D2R partial agonists that aimed to mimic aripiprazole failed to exert therapeutic effects in clinic. The present in vivo study aimed to investigate the effects of aripiprazole on the D2R downstream cAMP-PKA and Akt GSK3beta signalling pathways in comparison with a D2R antagonist--haloperidol and a D2R partial agonist--bifeprunox. Rats were injected once with aripiprazole (0.75 mg/kg, i.p.), bifeprunox (0.8 mg/kg, i.p.), haloperidol (0.1 mg/kg, i.p.) or vehicle. Five brain regions--the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), ventral tegmental area (VTA) and substantia nigra (SN) were collected. The protein levels of PKA, Akt and GSK3beta were measured by Western Blotting; the cAMP levels were examined by ELISA tests. The results showed that aripiprazole presented similar acute effects on PKA expression to haloperidol, but not bifeprunox, in the CPU and VTA. Additionally, aripiprazole was able to increase the phosphorylation of GSK3beta in the PFC, NAc, CPu and SN, respectively, which cannot be achieved by bifeprunox and haloperidol. These results suggested that acute treatment of aripiprazole had differential effects on the cAMP-PKA and Akt-GSK3beta signalling pathways from haloperidol and bifeprunox in these brain areas. This study further indicated that, by comparison with bifeprunox, the unique pharmacological profile of aripiprazole may be attributed to the relatively lower intrinsic activity at D2R. PMID- 26162084 TI - Cauliflower mosaic virus Transcriptome Reveals a Complex Alternative Splicing Pattern. AB - The plant pararetrovirus Cauliflower mosaic virus (CaMV) uses alternative splicing to generate several isoforms from its polycistronic pregenomic 35S RNA. This pro-cess has been shown to be essential for infectivity. Previous works have identified four splice donor sites and a single splice acceptor site in the 35S RNA 5' region and suggested that the main role of CaMV splicing is to downregulate expression of open reading frames (ORFs) I and II. In this study, we show that alternative splicing is a conserved process among CaMV isolates. In Cabb B-JI and Cabb-S isolates, splicing frequently leads to different fusion between ORFs, particularly between ORF I and II. The corresponding P1P2 fusion proteins expressed in E. coli interact with viral proteins P2 and P3 in vitro. However, they are detected neither during infection nor upon transient expression in planta, which suggests rapid degradation after synthesis and no important biological role in the CaMV infectious cycle. To gain a better understanding of the functional relevance of 35S RNA alternative splicing in CaMV infectivity, we inactivated the previously described splice sites. All the splicing mutants were as pathogenic as the corresponding wild-type isolate. Through RT-PCR-based analysis we demonstrate that CaMV 35S RNA exhibits a complex splicing pattern, as we identify new splice donor and acceptor sites whose selection leads to more than thirteen 35S RNA isoforms in infected turnip plants. Inactivating splice donor or acceptor sites is not lethal for the virus, since disrupted sites are systematically rescued by the activation of cryptic and/or seldom used splice sites. Taken together, our data depict a conserved, complex and flexible process, involving multiple sites, that ensures splicing of 35S RNA. PMID- 26162085 TI - A Systematic Review of Tobacco Smoking Prevalence and Description of Tobacco Control Strategies in Sub-Saharan African Countries; 2007 to 2014. AB - OBJECTIVE: To systematically review current smoking prevalence among adults in sub-Saharan Africa from 2007 to May 2014 and to describe the context of tobacco control strategies in these countries. DATA SOURCES: Five databases, Medline, Embase, Africa-wide Information, Cinahl Plus, and Global Health were searched using a systematic search strategy. There were no language restrictions. STUDY SELECTION: 26 included studies measured current smoking prevalence in nationally representative adult populations in sub-Saharan African countries. DATA EXTRACTION: Study details were independently extracted using a standard datasheet. Data on tobacco control policies, taxation and trends in prices were obtained from the Implementation Database of the WHO FCTC website. RESULTS: Studies represented 13 countries. Current smoking prevalence varied widely ranging from 1.8% in Zambia to 25.8% in Sierra Leone. The prevalence of smoking was consistently lower in women compared to men with the widest gender difference observed in Malawi (men 25.9%, women 2.9%). Rwanda had the highest prevalence of women smokers (12.6%) and Ghana had the lowest (0.2%). Rural, urban patterns were inconsistent. Most countries have implemented demand-reduction measures including bans on advertising, and taxation rates but to different extents. CONCLUSION: Smoking prevalence varied widely across sub-Saharan Africa, even between similar country regions, but was always higher in men. High smoking rates were observed among countries in the eastern and southern regions of Africa, mainly among men in Ethiopia, Malawi, Rwanda, and Zambia and women in Rwanda and rural Zambia. Effective action to reduce smoking across sub-Saharan Africa, particularly targeting population groups at increased risk remains a pressing public health priority. PMID- 26162087 TI - Risk of Fetal Death after Treatment with Antipsychotic Medications during Pregnancy. AB - BACKGROUND: Antipsychotic medications are increasingly used during pregnancy. Nevertheless, fetal risks are still not fully studied. It is currently unclear whether the antipsychotic treatment might induce a higher risk of fetal death. We aimed to determine if use of antipsychotic medication during pregnancy is associated with an increased risk of spontaneous abortion or stillbirth. METHODS: In a historical cohort study, we identified all clinically recognized pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319). Exposure was defined as any prescription of antipsychotic medications redeemed by the pregnant women during the exposure window, and recorded in the Danish National Prescription Register. Outcome was defined as any spontaneous abortion or stillbirth recorded in the Danish National Hospital Register and the Danish Medical Birth Register respectively. RESULTS: Women exposed to antipsychotic medications during pregnancy had a 34% higher risk of spontaneous abortion (adjusted relative risk = 1.34; 95% confidence interval = 1.22; 1.46) compared to unexposed women, but a similar risk compared to women exposed prior to (but not during) pregnancy (adjusted relative risk = 1.04; 95% confidence interval = 0.93; 1.17). The risk of spontaneous abortion was not increased in exposed pregnancies when compared to unexposed pregnancies in the same women (adjusted hazard ratio = 1.11; 95% CI = 0.94; 1.31). A twofold higher risk of stillbirth was found in women exposed to antipsychotic medications compared with unexposed women (relative risk = 2.27; 95% confidence interval = 1.45; 3.55) and compared with women exposed only prior to pregnancy (relative risk = 2.06; 95% confidence interval = 1.01; 4.19). CONCLUSIONS: The increased risk of spontaneous abortion found in women treated with antipsychotic medications during pregnancy is most likely due to confounding factors. The risk of stillbirth was twofold higher in pregnancies exposed to antipsychotic medication during pregnancy. Treatment with antipsychotic medications during pregnancy requires careful consideration. PMID- 26162086 TI - Self-Management and Self-Management Support Outcomes: A Systematic Review and Mixed Research Synthesis of Stakeholder Views. AB - INTRODUCTION: Self-management has received growing attention as an effective approach for long-term condition management. Little is known about which outcomes of supported self-management are valued by patients, their families, health professionals and those who commission self-management services. This study systematically reviewed published empirical evidence in accordance with PRISMA guidelines to determine the outcomes of self-management valued by these key stakeholder groups, using three prominent exemplar conditions: colorectal cancer, diabetes and stroke. AIM: To systematically review the literature to identify which generic outcomes of self-management have been targeted and are considered important using three exemplar conditions (colorectal cancer, diabetes and stroke), which collectively have a range of features that are likely to be representative of generic self-management issues. METHODS: Systematic searching of nine electronic databases was conducted in addition to hand searches of review articles. Abstracts were identified against inclusion criteria and appraised independently by two reviewers, using a critical appraisal tool. Synthesis of findings was conducted using mixed research synthesis. RESULTS: Over 20,536 abstracts were screened. 41 studies which met the review criteria were fully retrieved and appraised. The majority of evidence related to diabetes. Few studies directly focussed on stakeholders' views concerning desired self management outcomes; the majority of evidence was derived from studies focusing upon the experience of self-management. The views of health care commissioners were absent from the literature. We identified that self-management outcomes embrace a range of indicators, from knowledge, skills, and bio-psychosocial markers of health through to positive social networks. CONCLUSIONS: Patients', families', health professionals' and commissioners' views regarding which outcomes of self-management are important have not been clearly elicited. The extent to which bio-psychosocial indicators relate to successful self-management from the perspectives of all groups of stakeholders is unknown. Further investigation regarding which self-management outcomes are considered important by all stakeholders is necessary to guide the commissioning and design of future self-management services. PMID- 26162089 TI - A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania. AB - Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and species specific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1-2 years, those aged 3 and 4-5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem. PMID- 26162088 TI - Novel recA-Independent Horizontal Gene Transfer in Escherichia coli K-12. AB - In bacteria, mechanisms that incorporate DNA into a genome without strand transfer proteins such as RecA play a major role in generating novelty by horizontal gene transfer. We describe a new illegitimate recombination event in Escherichia coli K-12: RecA-independent homologous replacements, with very large (megabase-length) donor patches replacing recipient DNA. A previously uncharacterized gene (yjiP) increases the frequency of RecA-independent replacement recombination. To show this, we used conjugal DNA transfer, combining a classical conjugation donor, HfrH, with modern genome engineering methods and whole genome sequencing analysis to enable interrogation of genetic dependence of integration mechanisms and characterization of recombination products. As in classical experiments, genomic DNA transfer begins at a unique position in the donor, entering the recipient via conjugation; antibiotic resistance markers are then used to select recombinant progeny. Different configurations of this system were used to compare known mechanisms for stable DNA incorporation, including homologous recombination, F'-plasmid formation, and genome duplication. A genome island of interest known as the immigration control region was specifically replaced in a minority of recombinants, at a frequency of 3 X 10(-12) CFU/recipient per hour. PMID- 26162090 TI - Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection. AB - BACKGROUND: Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. METHODS: In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. RESULTS: Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. CONCLUSION: By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection. PMID- 26162092 TI - Hydroprocessing of Jatropha Oil for Production of Green Diesel over Non-sulfided Ni-PTA/Al2O3 Catalyst. AB - The non-sulfided Ni-PTA/Al2O3 catalyst was developed to produce green diesel from the hydroprocessing of Jatropha oil. The Ni-PTA/Al2O3 catalyst was prepared by one-pot synthesis of Ni/Al2O3 with the co-precipitation method and then impregnanting Ni/Al2O3 with PTA solution. The catalysts were characterized with BET, SEM-EDX, TEM, XRD, XPS, TGA and NH3-TPD. The Ni and W species of the Ni PTA/Al2O3 catalyst were much more homogeneously distributed on the surface than that of commercial Al2O3. Catalytic performance in the hydroprocessing of Jatropha oil was evaluated by GC. The maximum conversion of Jatropha oil (98.5 wt%) and selectivity of the C15-C18 alkanes fraction (84.5 wt %) occurred at 360 degrees C, 3.0 MPa, 0.8 h(-1). The non-sulfided Ni-PTA/Al2O3 catalyst is more environmentally friendly than the conventional sulfided hydroprocessing catalyst, and it exhibited the highest catalytic activity than the Ni-PTA catalyst supported with commercial Al2O3 grain and Al2O3 powder. PMID- 26162091 TI - Retinoic Acid Induces Embryonic Stem Cell Differentiation by Altering Both Encoding RNA and microRNA Expression. AB - Retinoic acid (RA) is a vitamin A metabolite that is essential for early embryonic development and promotes stem cell neural lineage specification; however, little is known regarding the impact of RA on mRNA transcription and microRNA levels on embryonic stem cell differentiation. Here, we present mRNA microarray and microRNA high-output sequencing to clarify how RA regulates gene expression. Using mRNA microarray analysis, we showed that RA repressed pluripotency-associated genes while activating ectoderm markers in mouse embryonic stem cells (mESCs). Moreover, RA modulated the DNA methylation of mESCs by altering the expression of epigenetic-associated genes such as Dnmt3b and Dnmt3l. Furthermore, H3K4me2, a pluripotent histone modification, was repressed by RA stimulation. From microRNA sequence data, we identified two downregulated microRNAs, namely, miR-200b and miR-200c, which regulated the pluripotency of stem cells. We found that miR-200b or miR-200c deficiency suppressed the expression of pluripotent genes, including Oct4 and Nanog, and activated the expression of the ectodermal marker gene Nestin. These results demonstrate that retinoid induces mESCs to differentiate by regulating miR-200b/200c. Our findings provide the landscapes of mRNA and microRNA gene networks and indicate the crucial role of miR-200b/200c in the RA-induced differentiation of mESCs. PMID- 26162093 TI - Comparison of Bone Mineral Density between Urban and Rural Areas: Systematic Review and Meta-Analysis. AB - BACKGROUND: Studies from high income countries (HIC) have generally shown higher osteoporotic fracture rates in urban areas than rural areas. Low bone mineral density (BMD) increases susceptibility to fractures. This review aimed to assess whether urbanicity is consistently associated with lower BMD globally. METHOD: Ovid MEDLINE, EMBASE, and Global Health (-April 2013) were searched for articles investigating differences in bone mineral content (BMC) or BMD between urban and rural areas. Ratio of means (RoM) of BMD were used to estimate effect sizes in meta-analysis, with an exception for one study that only presented BMC data. RESULTS: Fifteen articles from eleven distinct populations were included in the review; seven populations from four high income countries and four from three low and middle income countries (LMIC). Meta-analysis showed conflicting evidence for urban-rural difference in BMD; studies from high income countries generally showed higher BMD in rural areas while the results were more mixed in studies from low and middle income countries (HIC RoM = 0.05; 95% CI: 0.03 to 0.06; LMIC RoM = -0.04: 95% CI: -0.1 to 0.01). CONCLUSIONS: Urban-rural differences of bone mineral density may be context-specific. BMD may be higher in urban areas in some lower income countries. More studies with robust designs and analytical techniques are needed to understand mechanisms underlying the effects of urbanization on bone mass accrual and loss. PMID- 26162094 TI - Efficacy of Recombinant Canine Distemper Virus Expressing Leishmania Antigen against Leishmania Challenge in Dogs. AB - Canine distemper virus (CDV) vaccination confers long-term protection against CDV reinfection. To investigate the utility of CDV as a polyvalent vaccine vector for Leishmania, we generated recombinant CDVs, based on an avirulent Yanaka strain, that expressed Leishmania antigens: LACK, TSA, or LmSTI1 (rCDV-LACK, rCDV-TSA, and rCDV-LmSTI1, respectively). Dogs immunized with rCDV-LACK were protected against challenge with lethal doses of virulent CDV, in the same way as the parental Yanaka strain. To evaluate the protective effects of the recombinant CDVs against cutaneous leishmaniasis in dogs, dogs were immunized with one recombinant CDV or a cocktail of three recombinant CDVs, before intradermal challenge (in the ears) with infective-stage promastigotes of Leishmania major. Unvaccinated dogs showed increased nodules with ulcer formation after 3 weeks, whereas dogs immunized with rCDV-LACK showed markedly smaller nodules without ulceration. Although the rCDV-TSA- and rCDV-LmSTI1-immunized dogs showed little protection against L. major, the cocktail of three recombinant CDVs more effectively suppressed the progression of nodule formation than immunization with rCDV-LACK alone. These results indicate that recombinant CDV is suitable for use as a polyvalent live attenuated vaccine for protection against both CDV and L. major infections in dogs. PMID- 26162095 TI - Neutralizing Anti-IL20 Antibody Treatment Significantly Modulates Low Grade Inflammation without Affecting HbA1c in Type 2 Diabetic db/db Mice. AB - Low grade inflammation is present in pre-clinical and human type 2 diabetes. In this process, several cytokines like IL-1beta and inflammatory cells like macrophages are activated and demonstrated to participate to the disease initiation and progression. IL-20 is a cytokine known to play non-redundant roles in progression of several inflammatory diseases. To address the therapeutic effect of inhibiting the IL-20 pathway in diabetes, diabetic db/db mice were treated with neutralizing anti-IL20 antibodies in vivo and both metabolic and inflammatory parameters were followed. Diabetic islets expressed the IL-20 cytokine and all IL-20 receptor components in elevated levels compared to resting non-diabetic islets. Islets were responsive to ex vivo IL-20 stimulation measured as SOCS induction and KC and IL-6 production. Neutralizing anti-IL20 treatment in vivo had no effect on HbA1c or weight although the slope of blood glucose increase was lowered. In contrast, anti-IL20 treatment significantly reduced the systemic low-grade inflammation and modulated the local pancreatic immunity. Significant reduction of the systemic IL-1beta and MCP-1 was demonstrated upon anti-IL20 treatment which was orchestrated with a reduced RANTES, IL-16 and IL-2 but increased TIMP-1, MCP-1 and IL-6 protein expression locally in the pancreas. Interestingly, anti-IL20 treatment induced an expansion of the myeloid suppressor CD11bGr1int macrophage while reducing the number of CD8 T cells. Taken together, anti-IL20 treatment showed moderate effects on metabolic parameters, but significantly altered the low grade local and systemic inflammation. Hence, future combination therapies with anti-IL20 may provide beneficial therapeutic effects in type 2 diabetes through a reduction of inflammation. PMID- 26162096 TI - AMPK Signaling Involvement for the Repression of the IL-1beta-Induced Group IIA Secretory Phospholipase A2 Expression in VSMCs. AB - Secretory Phospholipase A2 of type IIA (sPLA2 IIA) plays a crucial role in the production of lipid mediators by amplifying the neointimal inflammatory context of the vascular smooth muscle cells (VSMCs), especially during atherogenesis. Phenformin, a biguanide family member, by its anti-inflammatory properties presents potential for promoting beneficial effects upon vascular cells, however its impact upon the IL-1beta-induced sPLA2 gene expression has not been deeply investigated so far. The present study was designed to determine the relationship between phenformin coupling AMP-activated protein kinase (AMPK) function and the molecular mechanism by which the sPLA2 IIA expression was modulated in VSMCs. Here we find that 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleotide (AICAR) treatment strongly repressed IL-1beta-induced sPLA2 expression at least at the transcriptional level. Our study reveals that phenformin elicited a dose dependent inhibition of the sPLA2 IIA expression and transient overexpression experiments of constitutively active AMPK demonstrate clearly that AMPK signaling is involved in the transcriptional inhibition of sPLA2-IIA gene expression. Furthermore, although the expression of the transcriptional repressor B-cell lymphoma-6 protein (BCL-6) was markedly enhanced by phenformin and AICAR, the repression of sPLA2 gene occurs through a mechanism independent of BCL-6 DNA binding site. In addition we show that activation of AMPK limits IL-1beta-induced NF-kappaB pathway activation. Our results indicate that BCL-6, once activated by AMPK, functions as a competitor of the IL-1beta induced NF-kappaB transcription complex. Our findings provide insights on a new anti-inflammatory pathway linking phenformin, AMPK and molecular control of sPLA2 IIA gene expression in VSMCs. PMID- 26162097 TI - Pollen-Mediated Gene Flow in Maize: Implications for Isolation Requirements and Coexistence in Mexico, the Center of Origin of Maize. AB - Mexico, the center of origin of maize (Zea mays L.), has taken actions to preserve the identity and diversity of maize landraces and wild relatives. Historically, spatial isolation has been used in seed production to maintain seed purity. Spatial isolation can also be a key component for a strategy to minimize pollen-mediated gene flow in Mexico between transgenic maize and sexually compatible plants of maize conventional hybrids, landraces, and wild relatives. The objective of this research was to generate field maize-to-maize outcrossing data to help guide coexistence discussions in Mexico. In this study, outcrossing rates were determined and modeled from eight locations in six northern states, which represent the most economically important areas for the cultivation of hybrid maize in Mexico. At each site, pollen source plots were planted with a yellow-kernel maize hybrid and surrounded by plots with a white-kernel conventional maize hybrid (pollen recipient) of the same maturity. Outcrossing rates were then quantified by assessing the number of yellow kernels harvested from white-kernel hybrid plots. The highest outcrossing values were observed near the pollen source (12.9% at 1 m distance). The outcrossing levels declined sharply to 4.6, 2.7, 1.4, 1.0, 0.9, 0.5, and 0.5% as the distance from the pollen source increased to 2, 4, 8, 12, 16, 20, and 25 m, respectively. At distances beyond 20 m outcrossing values at all locations were below 1%. These trends are consistent with studies conducted in other world regions. The results suggest that coexistence measures that have been implemented in other geographies, such as spatial isolation, would be successful in Mexico to minimize transgenic maize pollen flow to conventional maize hybrids, landraces and wild relatives. PMID- 26162098 TI - SS1 (NAL1)- and SS2-Mediated Genetic Networks Underlying Source-Sink and Yield Traits in Rice (Oryza sativa L.). AB - Source leaf/sink capacity (SS) traits are important determinants of grain yield (GY) of rice. To understand the genetic basis of the SS relationship in rice, five SS and GY traits of rice were genetically dissected using two reciprocal introgression populations. Seventy-three QTL affecting the SS and GY traits were identified, most of which were detected in one of the parental genetic backgrounds (GBs). Two major QTL at bins 4.7 (SS1) and 3.12 (SS2) were associated consistently with all measured SS and yield traits in both GBs across two contrasting environments. Strong interactions between SS1/SS2 and the detected QTL led us to the discovery of genetic networks affecting the SS and GY traits. The SS1 acted as a regulator controlling two groups of downstream QTL affecting the source leaf width and grain number per panicle (GNP). SS2 functioned as a regulator positively regulating different groups of downstream QTL affecting the source leaf length, GNP, grain weight, and GY. Map-based cloning of SS1 indicates that SS1 is NAL1 involved in polar auxin/IAA transport. Different alleles at NAL1 were apparently able to qualitatively and/or quantitatively control the IAA transport from the apical meristem to different plant tissues and thus regulate those downstream loci/pathways controlling different SS traits of rice. There was a functional allele and a non-functional mutation in the parents at each of the QTL downstream of SS1 or SS2, which were detectable only in the presence of the functional allele of SS1 or SS2. Our results provided direct evidence that SS and yield traits in rice are controlled by complex signaling pathways and suggest further improvement of rice yield potential with enhanced and balanced SS relationships can be achieved by accurately manipulating allelic combinations at loci in the SS1 and SS2 mediated pathways. PMID- 26162099 TI - Genogeography and Immune Epitope Characteristics of Hepatitis B Virus Genotype C Reveals Two Distinct Types: Asian and Papua-Pacific. AB - Distribution of hepatitis B virus (HBV) genotypes/subgenotypes is geographically and ethnologically specific. In the Indonesian archipelago, HBV genotype C (HBV/C) is prevalent with high genome variability, reflected by the presence of 13 of currently existing 16 subgenotypes. We investigated the association between HBV/C molecular characteristics with host ethnicity and geographical distribution by examining various subgenotypes of HBV/C isolates from the Asia and Pacific region, with further analysis on the immune epitope characteristics of the core and surface proteins. Phylogenetic tree was constructed based on complete HBV/C genome sequences from Asia and Pacific region, and genetic distance between isolates was also examined. HBV/C surface and core immune epitopes were analyzed and grouped by comparing the amino acid residue characteristics and geographical origins. Based on phylogenetic tree and geographical origins of isolates, two major groups of HBV/C isolates--East-Southeast Asia and Papua-Pacific--were identified. Analysis of core and surface immune epitopes supported these findings with several amino acid substitutions distinguishing the East-Southeast Asia isolates from the Papua-Pacific isolates. A west-to-east gradient of HBsAg subtype distribution was observed with adrq+ prominent in the East and Southeast Asia and adrq- in the Pacific, with several adrq-indeterminate subtypes observed in Papua and Papua New Guinea (PNG). This study indicates that HBV/C isolates can be classified into two types, the Asian and the Papua-Pacific, based on the virus genome diversity, immune epitope characteristics, and geographical distribution, with Papua and PNG as the molecular evolutionary admixture region in the switching from adrq+ to adrq-. PMID- 26162100 TI - Antimicrobial Photoinactivation Using Visible Light Plus Water-Filtered Infrared A (VIS + wIRA) Alters In Situ Oral Biofilms. AB - Recently, growing attention has been paid to antimicrobial photodynamic therapy (aPDT) in dentistry. Changing the microbial composition of initial and mature oral biofilm by aPDT using visible light plus water-filtered infrared-A wavelengths (VIS + wIRA) has not yet been investigated. Moreover, most aPDT studies have been conducted on planktonic bacterial cultures. Therefore, in the present clinical study we cultivated initial and mature oral biofilms in six healthy volunteers for 2 hours or 3 days, respectively. The biofilms were treated with aPDT using VIS+wIRA (200 mW cm(-2)), toluidine blue (TB) and chlorine e6 (Ce6) for 5 minutes. Chlorhexidine treated biofilm samples served as positive controls, while untreated biofilms served as negative controls. After aPDT treatment the colony forming units (CFU) of the biofilm samples were quantified, and the surviving bacteria were isolated in pure cultures and identified using MALDI-TOF, biochemical tests and 16S rDNA-sequencing. aPDT killed more than 99.9% of the initial viable bacterial count and 95% of the mature oral biofilm in situ, independent of the photosensitizer. The number of surviving bacterial species was highly reduced to 6 (TB) and 4 (Ce6) in the treated initial oral biofilm compared to the 20 different species of the untreated biofilm. The proportions of surviving bacterial species were also changed after TB- and Ce6-mediated aPDT of the mature oral biofilm, resulting in a shift in the microbial composition of the treated biofilm compared to that of the control biofilm. In conclusion, aPDT using VIS + wIRA showed a remarkable potential to eradicate both initial and mature oral biofilms, and also to markedly alter the remaining biofilm. This encourages the clinical use of aPDT with VIS + wIRA for the treatment of periimplantitis and periodontitis. PMID- 26162101 TI - Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats. AB - INTRODUCTION: Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM). METHODS: Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period. RESULTS: Activity counts were increased in cats during treatment with daily meloxicam (p<0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042). CONCLUSIONS: Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease. PMID- 26162103 TI - Connecting Clinical Practice to Scientific Progress. PMID- 26162104 TI - Learning Styles: Concepts and Evidence. AB - The term "learning styles" refers to the concept that individuals differ in regard to what mode of instruction or study is most effective for them. Proponents of learning-style assessment contend that optimal instruction requires diagnosing individuals' learning style and tailoring instruction accordingly. Assessments of learning style typically ask people to evaluate what sort of information presentation they prefer (e.g., words versus pictures versus speech) and/or what kind of mental activity they find most engaging or congenial (e.g., analysis versus listening), although assessment instruments are extremely diverse. The most common-but not the only-hypothesis about the instructional relevance of learning styles is the meshing hypothesis, according to which instruction is best provided in a format that matches the preferences of the learner (e.g., for a "visual learner," emphasizing visual presentation of information). The learning-styles view has acquired great influence within the education field, and is frequently encountered at levels ranging from kindergarten to graduate school. There is a thriving industry devoted to publishing learning-styles tests and guidebooks for teachers, and many organizations offer professional development workshops for teachers and educators built around the concept of learning styles. The authors of the present review were charged with determining whether these practices are supported by scientific evidence. We concluded that any credible validation of learning-styles-based instruction requires robust documentation of a very particular type of experimental finding with several necessary criteria. First, students must be divided into groups on the basis of their learning styles, and then students from each group must be randomly assigned to receive one of multiple instructional methods. Next, students must then sit for a final test that is the same for all students. Finally, in order to demonstrate that optimal learning requires that students receive instruction tailored to their putative learning style, the experiment must reveal a specific type of interaction between learning style and instructional method: Students with one learning style achieve the best educational outcome when given an instructional method that differs from the instructional method producing the best outcome for students with a different learning style. In other words, the instructional method that proves most effective for students with one learning style is not the most effective method for students with a different learning style. Our review of the literature disclosed ample evidence that children and adults will, if asked, express preferences about how they prefer information to be presented to them. There is also plentiful evidence arguing that people differ in the degree to which they have some fairly specific aptitudes for different kinds of thinking and for processing different types of information. However, we found virtually no evidence for the interaction pattern mentioned above, which was judged to be a precondition for validating the educational applications of learning styles. Although the literature on learning styles is enormous, very few studies have even used an experimental methodology capable of testing the validity of learning styles applied to education. Moreover, of those that did use an appropriate method, several found results that flatly contradict the popular meshing hypothesis. We conclude therefore, that at present, there is no adequate evidence base to justify incorporating learning-styles assessments into general educational practice. Thus, limited education resources would better be devoted to adopting other educational practices that have a strong evidence base, of which there are an increasing number. However, given the lack of methodologically sound studies of learning styles, it would be an error to conclude that all possible versions of learning styles have been tested and found wanting; many have simply not been tested at all. Further research on the use of learning styles assessment in instruction may in some cases be warranted, but such research needs to be performed appropriately. PMID- 26162102 TI - RFX2 Is a Major Transcriptional Regulator of Spermiogenesis. AB - Spermatogenesis consists broadly of three phases: proliferation of diploid germ cells, meiosis, and finally extensive differentiation of the haploid cells into effective delivery vehicles for the paternal genome. Despite detailed characterization of many haploid developmental steps leading to sperm, only fragmentary information exists on the control of gene expression underlying these processes. Here we report that the RFX2 transcription factor is a master regulator of genes required for the haploid phase. A targeted mutation of Rfx2 was created in mice. Rfx2-/- mice are perfectly viable but show complete male sterility. Spermatogenesis appears to progress unperturbed through meiosis. However, haploid cells undergo a complete arrest in spermatid development just prior to spermatid elongation. Arrested cells show altered Golgi apparatus organization, leading to a deficit in the generation of a spreading acrosomal cap from proacrosomal vesicles. Arrested cells ultimately merge to form giant multinucleated cells released to the epididymis. Spermatids also completely fail to form the flagellar axoneme. RNA-Seq analysis and ChIP-Seq analysis identified 139 genes directly controlled by RFX2 during spermiogenesis. Gene ontology analysis revealed that genes required for cilium function are specifically enriched in down- and upregulated genes showing that RFX2 allows precise temporal expression of ciliary genes. Several genes required for cell adhesion and cytoskeleton remodeling are also downregulated. Comparison of RFX2-regulated genes with those controlled by other major transcriptional regulators of spermiogenesis showed that each controls independent gene sets. Altogether, these observations show that RFX2 plays a major and specific function in spermiogenesis. PMID- 26162105 TI - Advances in Applying the Science of Learning and Instruction to Education. PMID- 26162106 TI - Amazon's Mechanical Turk: A New Source of Inexpensive, Yet High-Quality, Data? AB - Amazon's Mechanical Turk (MTurk) is a relatively new website that contains the major elements required to conduct research: an integrated participant compensation system; a large participant pool; and a streamlined process of study design, participant recruitment, and data collection. In this article, we describe and evaluate the potential contributions of MTurk to psychology and other social sciences. Findings indicate that (a) MTurk participants are slightly more demographically diverse than are standard Internet samples and are significantly more diverse than typical American college samples; (b) participation is affected by compensation rate and task length, but participants can still be recruited rapidly and inexpensively; (c) realistic compensation rates do not affect data quality; and (d) the data obtained are at least as reliable as those obtained via traditional methods. Overall, MTurk can be used to obtain high-quality data inexpensively and rapidly. PMID- 26162107 TI - Best Friends: Alliances, Friend Ranking, and the MySpace Social Network. AB - Like many topics of psychological research, the explanation for friendship is at once intuitive and difficult to address empirically. These difficulties worsen when one seeks, as we do, to go beyond "obvious" explanations ("humans are social creatures") to ask deeper questions, such as "What is the evolved function of human friendship?" In recent years, however, a new window into human behavior has opened as a growing fraction of people's social activity has moved online, leaving a wealth of digital traces behind. One example is a feature of the MySpace social network that allows millions of users to rank their "Top Friends." In this study, we collected over 10 million people's friendship decisions from MySpace to test predictions made by hypotheses about human friendship. We found particular support for the alliance hypothesis, which holds that human friendship is caused by cognitive systems that function to create alliances for potential disputes. Because an ally's support can be undermined by a stronger outside relationship, the alliance model predicts that people will prefer partners who rank them above other friends. Consistent with the alliance model, we found that an individual's choice of best friend in MySpace is strongly predicted by how partners rank that individual. PMID- 26162108 TI - Building a Better America-One Wealth Quintile at a Time. AB - Disagreements about the optimal level of wealth inequality underlie policy debates ranging from taxation to welfare. We attempt to insert the desires of "regular" Americans into these debates, by asking a nationally representative online panel to estimate the current distribution of wealth in the United States and to "build a better America" by constructing distributions with their ideal level of inequality. First, respondents dramatically underestimated the current level of wealth inequality. Second, respondents constructed ideal wealth distributions that were far more equitable than even their erroneously low estimates of the actual distribution. Most important from a policy perspective, we observed a surprising level of consensus: All demographic groups-even those not usually associated with wealth redistribution such as Republicans and the wealthy-desired a more equal distribution of wealth than the status quo. PMID- 26162109 TI - Consensus at the Heart of Division: Commentary on Norton and Ariely (2011). AB - We argue that seemingly deep-seated partisan divisions may be built on a foundation of surprising consensus, not only in terms of the wealth distributions that people prefer (Norton & Ariely, 2011, this issue), but also in the gut-level moral reactions and beliefs about money and happiness that may underlie those preferences. PMID- 26162110 TI - Procedural Justice Shapes Evaluations of Income Inequality: Commentary on Norton and Ariely (2011). AB - Research finds that people's reactions to inequality in wealth are more strongly related to their views about the fairness of the procedures of wealth allocation than they are by inequality itself. Hence, the key issue is whether people think markets are procedurally just allocation mechanisms. PMID- 26162111 TI - Unclear Implications: Commentary on Norton and Ariely (2011). AB - Despite the suggestiveness of their empirical findings, I argue that the implications of Norton and Ariely's work are unclear, both morally and politically. PMID- 26162112 TI - A New Veil of Ignorance? Commentary on Norton and Ariely (2011). AB - Norton and Ariely's (2011, this issue) finding that people prefer relatively equal distributions of wealth begs for further research. It is one thing to argue, as T. Frank (2004) has, that people vote against their interests. But Norton and Ariely seem to show that people vote against their preferences. What does that even mean, and how does it happen? PMID- 26162113 TI - Rebooting Psychotherapy Research and Practice to Reduce the Burden of Mental Illness. AB - Psychological interventions to treat mental health issues have developed remarkably in the past few decades. Yet this progress often neglects a central goal-namely, to reduce the burden of mental illness and related conditions. The need for psychological services is enormous, and only a small proportion of individuals in need actually receive treatment. Individual psychotherapy, the dominant model of treatment delivery, is not likely to be able to meet this need. Despite advances, mental health professionals are not likely to reduce the prevalence, incidence, and burden of mental illness without a major shift in intervention research and clinical practice. A portfolio of models of delivery will be needed. We illustrate various models of delivery to convey opportunities provided by technology, special settings and nontraditional service providers, self-help interventions, and the media. Decreasing the burden of mental illness also will depend on integrating prevention and treatment, developing assessment and a national database for monitoring mental illness and its burdens, considering contextual issues that influence delivery of treatment, and addressing potential tensions within the mental health professions. Finally, opportunities for multidisciplinary collaborations are discussed as key considerations for reducing the burden of mental illness. PMID- 26162114 TI - Evolutionary Theory and the Ultimate-Proximate Distinction in the Human Behavioral Sciences. AB - To properly understand behavior, we must obtain both ultimate and proximate explanations. Put briefly, ultimate explanations are concerned with why a behavior exists, and proximate explanations are concerned with how it works. These two types of explanation are complementary and the distinction is critical to evolutionary explanation. We are concerned that they have become conflated in some areas of the evolutionary literature on human behavior. This article brings attention to these issues. We focus on three specific areas: the evolution of cooperation, transmitted culture, and epigenetics. We do this to avoid confusion and wasted effort-dangers that are particularly acute in interdisciplinary research. Throughout this article, we suggest ways in which misunderstanding may be avoided in the future. PMID- 26162115 TI - Is It All Relative? Comparative Judgments and the Possible Improvement of Self Ratings and Ratings of Others. AB - We argue that various types of evaluative social judgments about the self or others (e.g., employee job performance ratings, self-reported attitudes, ratings of others' traits) may be obtained more accurately using comparative ratings rather than absolute ratings. Comparative ratings involve relative judgments of a target in comparison with other individuals or groups, whereas absolute ratings involve judgments of a target on scales that do not explicitly reference other people. In industrial-organizational, social, and personality psychology research that has compared the validity of comparative and absolute ratings, we have found evidence of more valid measurement as a result of comparative judgmental ratings, despite the nearly exclusive reliance on absolute judgmental ratings in these areas. We offer a social cognitive and evolutionary explanation in support of the hypothesis that humans may often be able to make more accurate ratings using comparative measures. We also recommend an agenda for greater exploitation and understanding of relative judgments in psychological research and practice. PMID- 26162116 TI - Too Much of a Good Thing: The Challenge and Opportunity of the Inverted U. AB - Aristotle proposed that to achieve happiness and success, people should cultivate virtues at mean or intermediate levels between deficiencies and excesses. In stark contrast to this assertion that virtues have costs at high levels, a wealth of psychological research has focused on demonstrating the well-being and performance benefits of positive traits, states, and experiences. This focus has obscured the prevalence and importance of nonmonotonic inverted-U-shaped effects, whereby positive phenomena reach inflection points at which their effects turn negative. We trace the evidence for nonmonotonic effects in psychology and provide recommendations for conceptual and empirical progress. We conclude that for psychology in general and positive psychology in particular, Aristotle's idea of the mean may serve as a useful guide for developing both a descriptive and a prescriptive account of happiness and success. PMID- 26162117 TI - Causation From Perception. AB - Beginning with the research of Albert Michotte, investigators have identified simple perceptual events that observers report as causal. For example, suppose a square moves across a screen and comes to a halt when it makes contact with a second square. If the second square then begins moving in the same direction, observers sometimes report that the first square "pushed" the second or "caused it to move." Based on such reports, Michotte claimed that people perceive causality, and a number of psychologists and philosophers have followed his lead. This article examines Michotte's hypothesis by comparing it with its chief rival: Observers possess representations of pushings, pullings, and other events in long term memory. A Michottean display triggers one of these representations, and the representation classifies the display as an instance of pushing (or pulling, etc.). According to this second explanation, recognizing an event as a pushing is similar to classifying an object as a cup or a dog. Data relevant to this debate come from infant and animal studies, cognitive and neuropsychological dissociation experiments, and studies of context effects and individual differences. However, a review of research in these paradigms finds no reason to prefer Michotte's theory over its competitor. PMID- 26162118 TI - Cognitive Dissonance: A History in Tweets. PMID- 26162119 TI - Cognitive "Category-Based Induction" Research and Social "Persuasion" Research Are Each About What Makes Arguments Believable: A Tale of Two Literatures. AB - Social and cognitive psychologists each study factors that influence the believability of arguments, but they have worked mostly in parallel. We briefly examine and compare the dominant theories explaining argument believability in the social persuasion literature and the cognitive category-based induction literature. Although the two areas ask similar questions, they use different paradigms to study different aspects of the issues. We describe each area's major paradigms and questions and then examine the conclusions that each area draws regarding the role of five variables important to argument believability: (a) the number of sources/premises, (b) the similarity between sources/premises, (c) individual differences in characteristics of the reasoner, (d) the available resources, and (e) the reasoner's background knowledge and beliefs. Comparing the two literatures provides a more complete picture of the factors influencing argument believability and provides fruitful new avenues for integration and exploration. PMID- 26162120 TI - The Attachment Paradox: How Can So Many of Us (the Insecure Ones) Have No Adaptive Advantages? AB - Bowlby's (1969/1982) attachment theory has generated an enormous body of research and conceptual elaborations. Although attachment theory and research propose that attachment security provides a person with many adaptive advantages during all phases of the life cycle, numerous studies indicate that almost half of the human species can be classified as insecurely attached or insecure with respect to attachment. It seems odd that evolution left humans in this vulnerable position unless there are some advantages, under at least some conditions, to anxious and avoidant attachment styles. We argue that a social group containing members with different attachment patterns may be more conducive to survival than a homogeneous group of securely attached individuals. In making this argument, we extend the scope of attachment theory and research by considering a broader range of adaptive functions of insecure attachment strategies. We also present preliminary data to support our argument. PMID- 26162121 TI - Episodic Future Thought: An Emerging Concept. AB - The ability to mentally simulate hypothetical scenarios is a rapidly growing area of research in both psychology and neuroscience. Episodic future thought, or the ability to simulate specific personal episodes that may potentially occur in the future, represents one facet of this general capacity that continues to garner a considerable amount of interest. The purpose of this article is to elucidate current knowledge and identify a number of unresolved issues regarding this specific mental ability. In particular, this article focuses on recent research findings from neuroimaging, neuropsychology, and clinical psychology that have demonstrated a close relation between episodic future thought and the ability to remember personal episodes from one's past. On the other hand, considerations of the role of abstracted (semantic) representations in episodic future thought have been noticeably absent in the literature. The final section of this article proposes that both episodic and semantic memory play an important role in the construction of episodic future thoughts and that their interaction in this process may be determined by the relative accessibility of information in memory. PMID- 26162122 TI - Moral Complexity: The Fatal Attraction of Truthiness and the Importance of Mature Moral Functioning. AB - Recently, intuitionist theories have been effective in capturing the academic discourse about morality. Intuitionist theories, like rationalist theories, offer important but only partial understanding of moral functioning. Both can be fallacious and succumb to truthiness: the attachment to one's opinions because they "feel right," potentially leading to harmful action or inaction. Both intuition and reasoning are involved in deliberation and expertise. Both are malleable from environmental and educational influence, making questions of normativity-which intuitions and reasoning skills to foster-of utmost importance. Good intuition and reasoning inform mature moral functioning, which needs to include capacities that promote sustainable human well-being. Individual capacities for habituated empathic concern and moral metacognition-moral locus of control, moral self-regulation, and moral self-reflection-comprise mature moral functioning, which also requires collective capacities for moral dialogue and moral institutions. These capacities underlie moral innovation and are necessary for solving the complex challenges humanity faces. PMID- 26162123 TI - Moral Psychology Must Not Be Based on Faith and Hope: Commentary on Narvaez (2010). AB - Narvaez (2010, this issue) calls for a moral psychology in which reasoning and intuitions are equal partners. But empirical research on the power of implicit processes and on the weakness of everyday reasoning indicates that the partnership is far from equal. The ancient rationalist faith that good reasoning can be taught and that it will lead to improved behavior is no longer justified. The social intuitionist model (Haidt, 2001) is a more realistic portrayal of the ways that moral intuition and reasoning work together. PMID- 26162124 TI - The Embodied Dynamism of Moral Becoming: Reply to Haidt (2010). PMID- 26162125 TI - The Costs and Benefits of Calculation and Moral Rules. AB - There has been a recent upsurge of research on moral judgment and decision making. One important issue with this body of work concerns the relative advantages of calculating costs and benefits versus adherence to moral rules. The general tenor of recent research suggests that adherence to moral rules is associated with systematic biases and that systematic cost-benefit analysis is a normatively superior decision strategy. This article queries both the merits of cost-benefit analyses and the shortcomings of moral rules. We argue that outside the very narrow domain in which consequences can be unambiguously anticipated, it is not at all clear that calculation processes optimize outcomes. In addition, there are good reasons to believe that following moral rules can lead to superior consequences in certain contexts. More generally, different modes of decision making can be seen as adaptations to particular environments. PMID- 26162126 TI - The Limits of Cost-Benefit Calculation: Commentary on Bennis, Medin, & Bartels (2010). AB - Bennis, Medin, and Bartels (2010, this issue) correctly identify real limits to the efficacy of cost-benefit analysis in comparison to moral rules. In this commentary, I suggest that those very same limits apply to decision making in general. Cost-benefit analysis may be the best way to arrive at decisions under a set of "closed-world assumptions" like those described by Bennis et al. But those assumptions virtually never hold, and in the absence of those assumptions, cost benefit analysis often substitutes counting for thinking. PMID- 26162127 TI - Situated Social Identities Constrain Morally Defensible Choices: Commentary on Bennis, Medin, & Bartels (2010). AB - Conceptual distinctions that loom large to philosophers-such as the distinction between utilitarian and deontic decision norms-may be far less salient to most other mortals. Building on an intuitive-politician model of judgment and choice and on the empirical work reported by Bennis, Medin, and Bartels (2010, this issue), we argue that the overriding goal of most decision makers in the paradigms under scrutiny is to offer judgments that are readily defensible and that reinforce their social identities as both cognitively flexible (responsive to evidence and cost-benefit considerations) and morally principled (prepared to defend sacred values and censure those who do not). People are best classified neither as utilitarians nor Kantians but rather as pragmatic social beings embedded in complex cultural-political systems. PMID- 26162128 TI - In Favor of Clear Thinking: Incorporating Moral Rules Into a Wise Cost-Benefit Analysis-Commentary on Bennis, Medin, & Bartels (2010). AB - Bennis, Medin, and Bartels (2010, this issue) have contributed an interesting article on the comparative benefit of moral rules versus cost-benefit analysis (CBA). Many of their specific comments are accurate, useful, and insightful. At the same time, we believe they have misrepresented CBA and have reached a set of conclusions that are misguided and, if adopted wholesale, potentially dangerous. Overall, they offer wise suggestions for making CBA more effective, rather than eliminating CBA as a decision-making tool. PMID- 26162129 TI - Perspectives on the Ecology of Decision Modes: Reply to Comments. PMID- 26162130 TI - Three Lessons Learned. AB - In this article, I describe varied observations from the past 60 years that motivated three significant changes in the assumptions I held as a young psychologist interested in the development of children. Aspects of these early assumptions penetrate a great deal of current research. The new beliefs are (a) a greater willingness to base concepts on patterns of measurements rather than single independent or dependent variables, (b) learning to include the physical features of the observational setting, including the procedure that generated the evidence, as well as the participants' gender, social class, and cultural background, as part of the concept, and (c) remaining aware of the possibility that the relations among continuous variables can change as a function of brain maturation during the early stages of childhood. PMID- 26162131 TI - Statistical Trends in Women's Participation in Science: Commentary on Valla and Ceci (2011). AB - Valla and Ceci (2011, this issue) describe the participation of women in science and claim that the increases in quantitative fields (e.g., mathematics, engineering, and physical sciences) are an exception to the statement that "Women's growth in the scientific workforce has been meteoric over the past 40 years" (p. 134). We disagree and present statistics demonstrating a more positive view of the increase of the number of women in quantitative fields. PMID- 26162132 TI - Dopamine and the Neural "Now": Essay and Review of Addiction: A Disorder of Choice. AB - Rather than view addiction as a disease, Heyman sees it as a choice-one that works like other choices, whereby immediate rewards outshine long-term gains. He rejects neuroscientific explanations of addictive behavior, because he believes they cast it as involuntary or disease-like. I argue that the disease-versus choice debate creates a false dichotomy: Neuroscience does not have to frame addiction as a disease. Rather, it can help explain how addicts make impulsive choices in the moment and distort appraisal and decision-making habits in the long run. Specifically, the salience of drug-related cues is enhanced by dopamine activity in the ventral striatum, orbitofrontal cortex, and amygdala, due to the intense hedonic impact of repeated drug experiences. Moreover, dopamine-based craving peaks when drug (or alcohol or gambling) rewards become available, in the moment, and this rapid increase in attractiveness preempts rational judgment. Finally, repeated dopamine enhancement modifies brain structures to maximize the appeal of addictive activities, minimize the appeal of competing rewards, and undermine the cognitive capacities necessary to choose between them. I conclude that addiction is not a monolithic state but a recurrent series of choices that permit negotiation, and sometimes cooperation, between immediate and long-range goals. PMID- 26162133 TI - Received Wisdom Regarding the Roles of Craving and Dopamine in Addiction: A Response to Lewis's Critique of Addiction: A Disorder of Choice. AB - Lewis's review of my book (2011, this issue) repeats widely shared understandings of the nature of addiction and the role that dopamine plays in the persistence of self-destructive drug use. These accounts depict addiction as a chronic relapsing disease and claim that drug-induced changes in dopamine function explain the transition from drug experimentation to compulsive drug use. In my book, I test the idea that addiction is a chronic, persistent state. Lewis fails to mention the results of the various tests, although they provide a handy test for his account of addiction and are surprising in light of the common verbal formula "addiction is a chronic, relapsing disease." Consequently, I review a few of the key findings in this response. Lewis faults me for not giving enough attention to dopamine. In my book, I conclude that there is more to the biology of addiction than dopamine, and in this response, I describe research that tests the idea that drug-induced increases in dopamine markedly reduce an individual's capacity to choose nondrug reinforcers. In one experiment, rats readily gave up cocaine for saccharin, even when they had been consuming massive amounts of the drug for weeks. Put more generally, well-established research results call for a revision of currently accepted understandings of addiction and the role that dopamine plays in drug use. PMID- 26162134 TI - Strengths and Limitations of Theoretical Explanations in Psychology: Introduction to the Special Section. PMID- 26162135 TI - Voodoo Correlations Are Everywhere-Not Only in Neuroscience. AB - A recent set of articles in Perspectives on Psychological Science discussed inflated correlations between brain measures and behavioral criteria when measurement points (voxels) are deliberately selected to maximize criterion correlations (the target article was Vul, Harris, Winkielman, & Pashler, 2009). However, closer inspection reveals that this problem is only a special symptom of a broader methodological problem that characterizes all paradigmatic research, not just neuroscience. Researchers not only select voxels to inflate effect size, they also select stimuli, task settings, favorable boundary conditions, dependent variables and independent variables, treatment levels, moderators, mediators, and multiple parameter settings in such a way that empirical phenomena become maximally visible and stable. In general, paradigms can be understood as conventional setups for producing idealized, inflated effects. Although the feasibility of representative designs is restricted, a viable remedy lies in a reorientation of paradigmatic research from the visibility of strong effect sizes to genuine validity and scientific scrutiny. PMID- 26162136 TI - The Problem of Circularity in Evidence, Argument, and Explanation. AB - A number of recent articles (Fiedler, 2011, this issue; Gigerenzer, 2009; Kriegeskorte, Simmons, Bellgowen, & Baker, 2009; Vul & Kanwisher, 2010) have highlighted seemingly circular arguments and explanations in psychological research, which suggests that the problem is rife within psychology. The article reviews the literature on circularity, and, in light of this, evaluates these recent examples from psychology to determine whether it is indeed circularity that is the underlying problem and to make suggestions for what paths improvements might pursue. PMID- 26162137 TI - Much Pain, Little Gain? Paradigm-Specific Models and Methods in Experimental Psychology. AB - Paradigm-oriented research strategies in experimental psychology have strengths and limitations. On the one hand, experimental paradigms play a crucial epistemic and heuristic role in basic psychological research. On the other hand, empirical research is often limited to the observed effects in a certain paradigm, and theoretical models are frequently tied to the particular features of the given paradigm. A paradigm-driven research strategy therefore jeopardizes the pursuit of research questions and theoretical models that go beyond a specific paradigm. As one example of a more integrative approach, recent research on illusory and spurious correlations has attempted to overcome the limitations of paradigm specific models in the context of biased contingency perception and social stereotyping. Last but not least, the use of statistical models for the analysis of elementary cognitive functions is a means toward a more integrative terminology and theoretical perspective across different experimental paradigms and research domains. PMID- 26162138 TI - Friends and Foes of Theory Construction in Psychological Science: Vague Dichotomies, Unified Theories of Cognition, and the New Experimentalism. AB - Newell (1973) criticized the use of vague theoretical dichotomies to account for narrowly defined empirical phenomena. Many of the problems raised by Newell persist today. We argue that these problems derive not from any peculiarity of psychological science but from the hindrances inherent to empirical theory testing. To show the contemporary relevance of these problems, we present two modern illustrations of the encumbrances faced by dichotomy-based research, we review some attempts to rely on nonempirical criteria to overcome the empirical impediments in theory testing, and we bring the question of theoretical mimicry to bear on these problems. Next, we discuss an alternative to theoretical dichotomies: the Unified Theories of Cognition (Newell, 1990). Finally, we introduce the "new experimentalism" approach in philosophy of science (Mayo, 1996), which provides a new perspective on theory construction in psychological science. We conclude with suggestions on how this new perspective can be implemented. PMID- 26162139 TI - Why the Cognitive Approach in Psychology Would Profit From a Functional Approach and Vice Versa. AB - Cognitively oriented psychologists often define behavioral effects in terms of mental constructs (e.g., classical conditioning as a change in behavior that is due to the formation of associations in memory) and thus effectively treat those effects as proxies for mental constructs. This practice can, however, hamper scientific progress. I argue that if psychologists would consistently define behavioral effects only in terms of the causal impact of elements in the environment (e.g., classical conditioning as a change in behavior that is due to the pairing of stimuli), they would adopt a functional approach that not only reveals the environmental causes of behavior but also optimizes cognitive research. The cognitive approach in turn strengthens the functional approach by facilitating the discovery of new causal relations between the environment and behavior. I thus propose a functional-cognitive framework for research in psychology that capitalizes on the mutually supportive nature of the functional and cognitive approaches in psychology. PMID- 26162140 TI - Editorial. PMID- 26162141 TI - Special Notice. PMID- 26162142 TI - Healing and Belonging: Godly Play in Pediatric Medicine and the Theology of Disability. AB - Godly Play can serve as an effective therapeutic and spiritual intervention for children experiencing physical, emotional, and/or spiritual stress. As many pediatric healthcare providers note, this type of intervention is an important component to a child's healing. This article situates Wolfson Children's Hospital's practice of Godly Play within two larger discussions that advocate for improved care for children with mental and physical impairments and concludes that this practice provides insight for the church and society to create a world in which children with mental and physical impairments belong. PMID- 26162143 TI - Sticks and Stones Can Break My Bones but Labels Scar My Soul. AB - Influenced by the followers of Descartes several centuries ago, philosophy, science and society took a turn in the road, one that has lead us astray. Mind was separated and cast away from its body, and so-called rationalism, reductionism and mechanism soon held sway over holism and humanism. Individuals were swept up, homogenized and subsumed under the provenance of arbitrarily created group norms for conduct. Those who did not follow were marginalized, or worse, demonized. Individuality, now being lost, inexorably would be replaced by all-encompassing clinical labels, that furthered the dehumanizing process begun and enforced so long ago. A new dialectic about the human circumstance based on humanism, empathy, understanding and respect, is proposed. PMID- 26162144 TI - The Chaplaincy Experience: Negotiating (Multi-Faith) Time and Space in a Northern English General Hospital. AB - This article reports on the inception and work of the first multi-faith chaplaincy team in a general hospital outside of London. The problematic beginnings are described as the team, previously run by and based on Anglican Christian ministry expanded to multi-faith care. The importance of the chapel/worship space in such a project diminished and chaplains and volunteer visitors of all faiths and none now minister in more secular spaces throughout the hospital and outside its walls. This is a reflection of their work becoming more interfaith as chaplains ministering to those of different faiths from their own evolved to a more spiritually rather than religiously oriented focus in generating patient-centred care in the context of a changing British culture, now considered simultaneously Christian, religiously plural, and secular. PMID- 26162145 TI - Pastoral Care and Counseling in Prison: What Works? PMID- 26162146 TI - Canadian Licensing Changes and the Anticipated Impact on Islamic Spiritual Care and Counseling Practice in Ontario. AB - This article highlights some significant aspects of the new regulations and the benefits of the College of Registered Psychotherapists and Registered Mental Health Therapists of Ontario (CRPO) with regard to the spiritual care and counseling practice of Muslim spiritual caregivers, including imams. PMID- 26162147 TI - Maturity: The Handiwork of Evolution. PMID- 26162148 TI - A Prayer for Healing Denied. PMID- 26162149 TI - Poetry. PMID- 26162150 TI - In the Media. PMID- 26162153 TI - Continuing Education Quiz. PMID- 26162156 TI - Detecting and Correcting the Lies That Data Tell. AB - Because of the way in which data are typically analyzed and interpreted, they frequently lie to researchers, leading to conclusions that are not only false but more complex than the underlying reality. The several examples of this presented in this article illustrate the possibility that although data may appear to indicate complex phenomena at the surface structure level, the phenomena may be quite simple at the deep structure level, suggesting the possibility of applying Occam's razor to achieve the scientific goal of parsimony. The approaches to data analysis described in this article may also lead to a solution to the serious problem of construct proliferation in psychology by demonstrating that many constructs are redundant with other existing constructs. The major obstacles to these outcomes are researchers' continued reliance on the use of statistical significance testing in data analysis and interpretation and the failure to correct for the distorting effects of sampling error, measurement error, and other artifacts. Some of these problems have been addressed by the now widespread use of meta-analysis, but examination of the meta-analyses appearing in Psychological Bulletin from 1978 to 2006 shows that most employ a statistically inappropriate model for meta-analysis (the fixed effects model) and that 90% do not correct for the biasing effects of measurement error. Hence, there is still a long way to go in the improvement of data analysis and interpretation methods. PMID- 26162157 TI - Rethinking Social Desirability Scales: From Impression Management to Interpersonally Oriented Self-Control. AB - Social desirability (specifically, impression management) scales are widely used by researchers and practitioners to screen individuals who bias self-reports in a self-favoring manner. These scales also serve to identify individuals at risk for psychological and health problems. The present review explores the evidence with regard to the ability of these scales to achieve these objectives. In the first part of the review, I present six criteria to evaluate impression management scales and conclude that they are unsatisfactory as measures of response style. Next, I explore what individual differences in impression management scores actually do measure. I compare two approaches: a defensiveness approach, which argues that these scales measure defensiveness that stems from vulnerable self esteem, and an adjustment approach, which suggests that impression management is associated with personal well-being and interpersonal adjustment. Data from a wide variety of fields including social behavior, affect and well-being, health, and job performance tend to favor the adjustment approach. Finally, I argue that scales measuring impression management should be redefined as measures of interpersonally oriented self-control that identify individuals who demonstrate high levels of self-control, especially in social contexts. PMID- 26162158 TI - Bite-Size Science: Relative Impact of Short Article Formats. AB - Critics have argued that publishing in psychology must become quicker and leaner. In response, some journals have adopted short article formats alongside regular articles. The citation impact of these formats was compared in a study of 1,735 articles published in Psychological Science, Cognition, and the Journal of Experimental Social Psychology over a 6-year period. Short articles received fewer citations on average but more citations on a per-page basis. They were only slightly less likely to have high impact. Short articles appear to garner scientific influence more efficiently than standard articles, supporting calls for their widespread adoption. PMID- 26162159 TI - Alcohol Myopia Revisited: Clarifying Aggression and Other Acts of Disinhibition Through a Distorted Lens. AB - The alcohol myopia model (AMM; Steele & Josephs, 1990) is reviewed in light of its unique ability to account for a variety of alcohol and nonalcohol-related disinhibited behaviors, particularly aggression. The AMM posits that alcohol has a narrowing, or a "myopic," effect on one's ability to attend to competing instigatory and inhibitory cues. Disinhibited behavior is presumed to occur when attention is directed toward salient provocative or instigatory cues rather than inhibitory cues. AMM research is reviewed with regard to stress and anxiety, risky sexual behavior, drinking and driving, suicide, disinhibited eating, smoking, and alcohol-related aggression. The AMM is also expanded by proposing five key mechanisms (i.e., negative affect, angry affect, hostile cognitive rumination, self-awareness, and empathy) that are likely to explain how the model is specifically involved in the alcohol-aggression relation. Finally, a number of public health interventions, extrapolated from the AMM, are proposed to stimulate future research directed at reducing the prevalence of alcohol-related violence. PMID- 26162160 TI - A New Social-Cognitive Developmental Perspective on Prejudice: The Interplay Between Morality and Group Identity. AB - We argue that prejudice should be investigated in the context of social-cognitive development and the interplay between morality and group identity. Our new perspective examines how children consider group identity (and group norms) along with their developing moral beliefs about fairness and justice. This is achieved by developing an integrated framework drawing on developmental and social psychological theories of prejudice. This synthesis results in a perspective that provides a more contextualized analysis of prejudice development than that previously offered by developmental theories. We describe research that supports our view that social norms, intergroup contact, and perceived outgroup threat affect the relative weight children place on moral and group-based criteria during the development of prejudice. PMID- 26162161 TI - A Theory of Human Needs Should Be Human-Centered, Not Animal-Centered: Commentary on Kenrick et al. (2010). AB - Kenrick et al. (2010, this issue) make an important contribution by presenting a theory of human needs within an evolutionary framework. In our opinion, however, this framework bypasses the human uniqueness that Maslow intended to capture in his theory. We comment on the unique power of culture in shaping human motivation at the phylogenetic, ontogenetic, and proximate levels. We note that culture-gene coevolution may be a more promising lead to a theory of human motivation than a mammalcentric evolutionary perspective. PMID- 26162162 TI - What Happened to Self-Actualization? Commentary on Kenrick et al. (2010). AB - Abraham Maslow's hierarchy of needs is one of psychology's genuinely good ideas and has had a sustained impact in and out of psychology. The revision of the hierarchy by Kenrick, Griskevicius, Neuberg, and Schaller (2010, this issue) is overdue and makes an important contribution by grounding the hierarchy in modern evolutionary thought. However, we suggest that it may be premature to remove self actualization from the hierarchy by reducing it to other needs associated with status and reproduction. PMID- 26162163 TI - The Purpose-Driven Life: Commentary on Kenrick et al. (2010). AB - The resurgence of motivation in social psychology has been a welcome addition to the cognitive revolution, though a theory-based approach to motivational content has remained conspicuously absent. Kenrick, Griskevicius, Neuberg, and Schaller (2010, this issue) dust off Maslow's hierarchy of needs and find this content in the form of evolutionarily inspired, fundamental motives. Their new framework unites functional, developmental, and proximal levels of analysis by showing how these levels complement rather than compete with each other. We highlight what we see as the especially valuable features of this framework and discuss its relevance for research on goal conflict, multigoal priming, and recent studies of goal scaffolding. We also suggest one main tweak to the theoretical foundation presented here that may bear greater empirical fruit. In sum, Kenrick and colleagues have reinvigorated a classic theory by integrating it with a modern understanding of human behavior's evolutionary roots. PMID- 26162164 TI - Human Motives, Happiness, and the Puzzle of Parenthood: Commentary on Kenrick et al. (2010). AB - It is presumed that happiness, and its associated positive emotions, signal to the individual that an adaptive problem has been solved, thus allowing her to shift attention to other concerns, perhaps those "higher" on the revised motivational hierarchy proposed by Kenrick et al (2010, this issue). In this commentary, we present a sampling of longitudinal and experimental evidence supporting two predictions: (a) that people will feel happy after realizing fundamental human motives, and (b) that in turn, the experience of happiness will galvanize people to fulfill these very motives. However, one conspicuous exception to our argument that happiness is both a consequence and a stimulus of human motives is parenthood, which paradoxically is associated with decrements in well-being. Two broad sets of explanations to account for this puzzle are discussed. The first involves evolutionary accounts: that children interfere with lower level needs, that short-term costs of having children are outweighed by long-term benefits, and that the modern-day context of raising children is at odds with our ancestors' environments. The second possibility involves measurement: namely, problems with study designs and the difficulty of capturing on paper or computer screen what is precisely so wonderful and elusive that children grant their parents. PMID- 26162165 TI - Pyramid Power: A Reply to Commentaries. AB - Four thoughtful commentaries identify important issues and insights pertaining to the pyramid of needs presented by Kenrick, Griskevicius, Neuberg, and Schaller (2010, this issue). Here, we offer additional thoughts on some of these issues and insights, with an emphasis on the logical implications that result from an evolutionary analysis of fundamental human needs. PMID- 26162166 TI - Editorial. PMID- 26162168 TI - The Use of Traumatic Biblical Narratives in Spiritual Recovery from Trauma: Theory and Case Study. AB - Scholars in different disciplines have begun to converge in their answer to the fundamental question, "what does it mean to be a unique person." Writers in the fields of psychology, neurology and theology have begun to address the fact that identity is tied to the narratives we create, more than the events that occur in life. Traumatic events in life can create discontinuities in that narrative that interfere with functioning. In this essay, I propose the use of traumatic Biblical narratives in pastoral counseling to assist the client in articulating personal traumatic episodes and beginning the process of integrating traumatic experiences and initiating growth. PMID- 26162169 TI - Clergy Stress through Working with Trauma: A Qualitative Study of Secondary Impact. AB - This article explores the impact upon clergy as a result of working with trauma within their pastoral ministry. The paper is unusual in that examines the toll exacted as part of their daily pastoral ministry in offering care and support to those who have encountered life's daily tragedies. Utilizing a sample of 16 serving Irish clergy Drawing on an Interpretative Phenomenological Analysis framework the data was organized into super-ordinate themes. Findings indicate that this is a challenging aspect of the ministry and one that can result in physical, cognitive and behavioural effects not only on those who provide the initial support but also in turn upon their informal support networks. PMID- 26162170 TI - Critically Engaging "Mutually Engaged Supervisory Processes": A Proposed Theory for CPE Supervisory Education. AB - Revisions to the processes for training and certifying supervisors continue to be debated within the Association for Clinical Pastoral Education (ACPE). In 2012 Ragsdale and colleagues published, "Mutually engaged supervisory processes," a qualitative research study utilizing grounded theory based on interviews with 19 recently certified Associate CPE Supervisors, of nine components that facilitate the development of CPE supervisory education students. In this article we critically engage this theory and the research upon which it is based. We also reflect on three issues highlighted by the theory: personal transformation in CPE supervisory education, how CPE supervisory education students develop theoretical foundations for their work, and engaging multicultural issues in supervisory education. We conclude that this theory offers ACPE the possibility of using research to guide future modifications to its practice of Supervisory education. PMID- 26162172 TI - Walking around the NICU, a Different Take on Miracles. PMID- 26162171 TI - Critically Engaging "Mutually Engaged Supervisory Processes" - A Response. PMID- 26162173 TI - Toward an Example Pastoral Care: Considering the Life of Jesus. PMID- 26162175 TI - Poetry. PMID- 26162174 TI - Affirmation of Uncertainty. PMID- 26162176 TI - IBCSR. PMID- 26162180 TI - The Journal of Pastoral Care and Counseling QUIZ (Winter 2014 Vol. 68, No. 4). PMID- 26162182 TI - General Evaluability Theory. AB - A central question in psychology and economics is the determination of whether individuals react differently to different values of a cared-about attribute (e.g., different income levels, different gas prices, and different ambient temperatures). Building on and significantly extending our earlier work on preference reversals between joint and separate evaluations, we propose a general evaluability theory (GET) that specifies when people are value sensitive and when people mispredict their own or others' value sensitivity. The GET can explain and unify many seemingly unrelated findings, ranging from duration neglect to affective forecasting errors and can generate many new research directions on topics ranging from temporal discounting to subjective well-being. PMID- 26162183 TI - Social Ecology: Lost and Found in Psychological Science. AB - This article presents a socioecological approach (accounting for physical, societal, and interpersonal environments) to psychological theorizing and research. First, we demonstrate that economic systems, political systems, religious systems, climates, and geography exert a distal yet important influence on human mind and behavior. Second, we summarize the historical precedents of socioecological psychology. There have been several waves of ecological movements with distinct emphases in the history of psychological science, such as K. Lewin's (1936, 1939) field theory and U. Bronfenbrenner's (1977) ecological approach to human development. Environmental and community psychologies, created in the late 1960s and early 1970s, promoted social activism through basic and applied research on ecological factors and social outcomes. Most recently, the rise of cultural psychology has encouraged psychologists to pay attention to cultural factors in basic psychological processes, but note that less attention has been given to socioecological factors per se. We highlight the benefits of bringing the socioecological perspective back to mainstream psychological theorizing and research. PMID- 26162184 TI - Causal Impact of Employee Work Perceptions on the Bottom Line of Organizations. AB - Perceptions of work conditions have proven to be important to the well-being of workers. However, customer loyalty, employee retention, revenue, sales, and profit are essential to the success of any business. It is known that these outcomes are correlated with employee attitudes and perceptions of work conditions, but the research into direction of causality has been inconclusive. Using a massive longitudinal database that included 2,178 business units in 10 large organizations, we found evidence supporting the causal impact of employee perceptions on these bottom-line measures; reverse causality of bottom-line measures on employee perceptions existed but was weaker. Managerial actions and practices can impact employee work conditions and employee perceptions of these conditions, thereby improving key outcomes at the organizational level. Perceptions of specific work conditions that engage employees in their work provide practical guidance in how best to manage people to obtain desired results. PMID- 26162185 TI - Culture and Psychological Science: Introduction to the Special Section. PMID- 26162186 TI - Why We Remember and What We Remember: Culture and Autobiographical Memory. AB - We examine cultural (mainly East and West) differences in the functions and contents of autobiographical memory. We discuss how cultural differences in physical environments, self-views, the motivation to self-enhance, concerns for behavioral and emotional regulation, socialization, and language affect the contents and use of memory. Cultural influences take place at the individual level of cognitive schemata and memory strategies, as well as the interpersonal sphere of daily mnemonic practices and exchanges. Autobiographical memory is categorically cultural. PMID- 26162187 TI - Culture and Judgment and Decision Making: The Constructivist Turn. AB - Cultural influences on individual judgment and decision making are increasingly understood in terms of dynamic constructive processing and the structures in social environments that shape distinct processing styles, directing initial attentional foci, activating particular judgment schemas and decision strategies, and ultimately reinforcing some judgment and decision making (JDM) patterns over others. These structures include the society's observable patterns of normative actions and responses, its prevalent forms of interpersonal interaction, the typical size and density of social networks, the ideational frames represented publically in texts and institutions, and so forth. We review this emerging perspective on culture and JDM in both economic and social domains, noting the distinctive insights it yields. We suggest new ways that cultural research is becoming relevant to mainstream JDM researchers, while also recognizing issues in need of further research. PMID- 26162188 TI - Cultures and Selves: A Cycle of Mutual Constitution. AB - The study of culture and self casts psychology's understanding of the self, identity, or agency as central to the analysis and interpretation of behavior and demonstrates that cultures and selves define and build upon each other in an ongoing cycle of mutual constitution. In a selective review of theoretical and empirical work, we define self and what the self does, define culture and how it constitutes the self (and vice versa), define independence and interdependence and determine how they shape psychological functioning, and examine the continuing challenges and controversies in the study of culture and self. We propose that a self is the "me" at the center of experience-a continually developing sense of awareness and agency that guides actions and takes shape as the individual, both brain and body, becomes attuned to various environments. Selves incorporate the patterning of their various environments and thus confer particular and culture-specific form and function to the psychological processes they organize (e.g., attention, perception, cognition, emotion, motivation, interpersonal relationship, group). In turn, as selves engage with their sociocultural contexts, they reinforce and sometimes change the ideas, practices, and institutions of these environments. PMID- 26162189 TI - Children's Integration in Communities and Segregation From People of Differing Ages. AB - This article reviews cultural differences in the extent of segregation of children from community life and their integration with people of differing ages, focusing especially on children's engagement with older children or similar-age children. We highlight cultural differences in children's everyday companionship with older children and with peers by discussing a study using naturalistic observations of young children's days in four cultural communities. Young children were more often involved with older children (who were often related to them) among the Efe of the Ituri Forest of the Democratic Republic of Congo and in the Guatemalan Mayan town of San Pedro, whereas middle-class European American children from two regions in the United States were more frequently involved with children of similar ages (who were often unrelated to them). The mainstream research focus on similar-age (unrelated) peer involvements, often regarded as the "norm," needs to be broadened to consider the various patterns of children's social engagements worldwide, which often involve integration of children in broader communities, engaging with adults and children of all ages. PMID- 26162190 TI - Current Perspectives in the Study of Personality Across Cultures. AB - A comprehensive conception of personality would incorporate dispositional traits, characteristic adaptations, and life narratives considered within evolutionary and cultural contexts (McAdams & Pals, 2006). In this article, I review evolutionary, cross-cultural, indigenous, and cultural psychology perspectives as they address these different aspects of personality across cultures. Evolutionary psychologists have focused most on evolved human nature (e.g., species-typical psychological mechanisms) and have recently considered evolutionary bases for heritable variation in dispositional traits. Cross-cultural psychologists have primarily addressed the universality of dispositional traits (e.g., the Five Factor Model) and characteristic adaptations (e.g., values, motives, and beliefs). Indigenous psychologists elaborate salient personality constructs for specific cultural groups, raising the question of whether these constructs represent culture-unique traits or culture-relevant expressions of universal dimensions (i.e., characteristic adaptations). Cultural psychologists de emphasize dispositional traits, propose cultural differences in characteristic adaptations (e.g., conceptions of personality and self) and life narratives, and investigate dynamic constructivist perspectives on culture. After the review, I consider what an integration of these perspectives might look like and offer suggestions for research. PMID- 26162191 TI - Moving Beyond Conventional Wisdom: Advancements in Cross-Cultural Theories of Leadership, Conflict, and Teams. AB - In this article, we discuss the importance of a cross-cultural approach to organizational behavior. To do so, we illustrate how cross-cultural research in the past two decades has enabled us to reconceptualize constructs, revise models, and extend boundary conditions in traditional organizational behavior theories. We focus on three domains-teams, leadership, and conflict-and review cross cultural empirical evidence that has extended several theories in each of these domains. We support the claim that even well-established organizational behavior theories vary in the extent to which they may be applied unilaterally across cultures, thus identifying the critical need to advance these theories via a cross-cultural research agenda. PMID- 26162192 TI - Culture and Well-Being: A New Inquiry Into the Psychological Wealth of Nations. AB - What is a good society? Philosophers from Plato to Bentham have argued that a good society is a happy society-namely, a society in which most citizens are happy and free from fear. Since the publication of The Wealth of Nations by Adam Smith in 1776, most economists have implicitly assumed that a happy society is a materially wealthy society. Thus, gross national product and related indices became the most popular indicators of the well-being of nations from the 1950s to date. Recently, however, prominent economists as well as political scientists, sociologists, and psychologists have shown that a happy society is not only a materially wealthy society but also a society in which citizens can trust one another, have a sense of freedom, and have close social relationships. The inquiry into the psychological wealth of nations, or the subjective well-being of nations, helps answer a fundamental question in philosophy and social sciences for millennia: "What is a good society?" PMID- 26162193 TI - Acculturation: When Individuals and Groups of Different Cultural Backgrounds Meet. AB - In cross-cultural psychology, one of the major sources of the development and display of human behavior is the contact between cultural populations. Such intercultural contact results in both cultural and psychological changes. At the cultural level, collective activities and social institutions become altered, and at the psychological level, there are changes in an individual's daily behavioral repertoire and sometimes in experienced stress. The two most common research findings at the individual level are that there are large variations in how people acculturate and in how well they adapt to this process. Variations in ways of acculturating have become known by the terms integration, assimilation, separation, and marginalization. Two variations in adaptation have been identified, involving psychological well-being and sociocultural competence. One important finding is that there are relationships between how individuals acculturate and how well they adapt: Often those who integrate (defined as being engaged in both their heritage culture and in the larger society) are better adapted than those who acculturate by orienting themselves to one or the other culture (by way of assimilation or separation) or to neither culture (marginalization). Implications of these findings for policy and program development and for future research are presented. PMID- 26162194 TI - Intersubjective Culture: The Role of Intersubjective Perceptions in Cross Cultural Research. AB - Intersubjective perceptions refer to shared perceptions of the psychological characteristics that are widespread within a culture. In this article, we propose the intersubjective approach as a new approach to understanding the role that culture plays in human behavior. In this approach, intersubjective perceptions, which are distinct from personal values and beliefs, mediate the effect of the ecology on individuals' responses and adaptations. We review evidence that attests to the validity and utility of the intersubjective approach in explicating culture's influence on human behaviors and discuss the implications of this approach for understanding the interaction between the individual, ecology, and culture; the nature of cultural competence; management of multicultural identities; cultural change; and measurement of culture. PMID- 26162195 TI - Introduction to the Special Issue: Genetics, Personalized Medicine, and Behavioral Intervention-Can This Combination Improve Patient Care? PMID- 26162196 TI - Mendelian Randomization for Strengthening Causal Inference in Observational Studies: Application to Gene * Environment Interactions. AB - Identification of environmentally modifiable factors causally influencing disease risk is fundamental to public-health improvement strategies. Unfortunately, observational epidemiological studies are limited in their ability to reliably identify such causal associations, reflected in the many cases in which conventional epidemiological studies have apparently identified associations that randomized controlled trials have failed to verify. The use of genetic variants as proxy measures of exposure -an application of the Mendelian randomization principle-can contribute to strengthening causal inference. Genetic variants are not subject to bias due to reverse causation (disease processes influencing exposure, rather than vice versa) or recall bias, and if simple precautions are applied, they are not influenced by confounding or attenuation by errors. The principles of Mendelian randomization are illustrated with specific reference to studies of the effects of alcohol intake on various health-related outcomes through the utilization of genetic variants related to alcohol metabolism (in ALDH2 and ADH1B). Ways of incorporating Gene * Environment interactions into the Mendelian randomization framework are developed, and the strengths and limitations of the approach discussed. PMID- 26162197 TI - Early Adversity and Developmental Outcomes: Interaction Between Genetics, Epigenetics, and Social Experiences Across the Life Span. AB - Longitudinal studies in humans demonstrate the association between prenatal and postnatal experiences of adversity and long-term changes in neurodevelopment. These studies raise the question of how experiences become incorporated at a biological level to induce persistent changes in functioning. Laboratory studies using animal models and recent analyses in human cohorts implicate epigenetic mechanisms as a possible route through which these environmental effects are achieved. In particular, there is evidence that changes in DNA methylation are associated with early life experiences with consequences for gene expression and behavior. Despite the potential stability of DNA methylation, it is apparent that this epigenetic mark can be dynamically modified through pharmacological targeting and behavioral experiences. Developmental plasticity may also be achieved through modification of the juvenile environment. Although these juvenile experiences may lead to common endpoints, there is evidence suggesting that the effects of early and later life experiences may be achieved by different molecular pathways. This review discusses evidence for the role of epigenetic mechanisms in shaping developmental trajectories in response to early life experience as well as the potential plasticity that can occur beyond the perinatal period. These studies have implications for approaches to intervention and suggest the importance of considering individual differences in genetic and epigenetic vulnerability in developing treatment strategies. PMID- 26162198 TI - Heterogeneity of Physical Function Responses to Exercise in Older Adults: Possible Contribution of Variation in the Angiotensin-1 Converting Enzyme (ACE) Gene? AB - Behavioral exercise interventions, aimed at improving either aerobic endurance or muscular strength, are currently the only therapy found, on average, to consistently retard loss of physical function in aging adults. However, not all individuals experience the same magnitude of benefit from a given exercise treatment, and certain persons may respond more favorably to a particular mode of exercise than another. Research now shows that genetic predisposition is one of the factors accounting for interindividual differences in responses to exercise as well as differences in the propensity to engage in exercise. This article discusses how a common variant in a single gene (the angiotensin-1 converting enzyme gene) could emerge as a prospective tool to identify older individuals more likely to benefit from and adhere to a specific type of exercise activity over another type. PMID- 26162199 TI - Erratum. PMID- 26162200 TI - Welcome to the new format of The Journal of Pastoral Care & Counseling. Introduction. PMID- 26162201 TI - Recognition and the Fleeting Glimpse of Intimacy: Tracing the Chaplain's Response to Ungrieved Death. AB - The article traces the response of the hospital chaplain witnessing ungrieved death. Linking grief with cultural recognition, the article analyzes the absence of grief on the occasion of death within outcast social spheres. It then outlines the ways chaplains both participate in the cultural norms that render lives ungrievable and, conversely, in the solidarity of God, who cares for every life and death. The article closes by situating the chaplain as a liminal figure and proposing liminality itself as an opportunity for solidarity. PMID- 26162202 TI - Drawing Close to the Brokenhearted: Pastoral Responses to Parents Grieving Stillbirth. AB - Despite its prevalence worldwide, stillbirth is poorly understood and rarely discussed. Accordingly, ministers and other pastoral caregivers are seldom prepared to counsel and console parents suffering from this type of infant loss and to effectively design, propose, and lead ministries within their faith communities for this grieving population. This article addresses the immediate pastoral needs of bereaved parents and proposes first and second order responses that ministers and faith communities can employ to compassionately and effectively care for parents suffering from the trauma of stillbirth. PMID- 26162203 TI - Spiritual Care Training Provided to Healthcare Professionals: A Systematic Review. AB - This systematic review was conducted to assess the outcomes of spiritual care training. It outlines the training outcomes based on participants' oral/written feedback, course evaluation and performance assessment. Intervention was defined as any form of spiritual care training provided to healthcare professionals studying/working in an academic and/or clinical setting. An online search was conducted in MEDLINE, EMBASE, CINAHL, Web of Science, ERIC, PsycINFO, ASSIA, CSA, ATLA and CENTRAL up to Week 27 of 2013 by two independent investigators to reduce errors in inclusion. Only peer-reviewed journal articles reporting on training outcomes were included. A primary keyword-driven search found 4912 articles; 46 articles were identified as relevant for final analysis. The narrative synthesis of findings outlines the following outcomes: (1) acknowledging spirituality on an individual level, (2) success in integrating spirituality in clinical practice, (3) positive changes in communication with patients. This study examines primarily pre/post-effects within a single cohort. Due to an average study quality, the reported findings in this review are to be seen as indicators at most. Nevertheless, this review makes evident that without attending to one'the repeliefs and needs, addressing spirituality in patients will not be forthcoming. It also demonstrates that spiritual care training may help to challenge the spiritual vacuum in healthcare institutions. PMID- 26162204 TI - The Intergenerational Transmission of Core Values in Clinical Supervision. AB - Four authors representing four generations of therapists reflect upon the role of core values that are communicated in the supervision hour. They further reflect upon how such values are transmitted from one generation of therapists to the next. Drawing upon their own experience of giving and receiving supervision, the authors hypothesize the existence of an intergenerational process by which values are passed on from one generation to the next. PMID- 26162205 TI - Cognitive-Existential Family Therapy: A Proposed Theoretical Integration Model for Pastoral Counselors. AB - Fundamental Christianity and psychology are frequently viewed as incompatible pursuits. However, proponents of the integrationist movement posit that pastoral counselors can utilize principles from psychology if they adopt the premise that all truth is God's truth. Assuming this perspective, Cognitive-Existential Family Therapy (CEFT) - a theoretical integration model compatible with Christian fundamentalism - is proposed. The philosophical assumptions and models of personality, health, and abnormality are explored. Additionally, the article provides an overview of the therapeutic process. PMID- 26162206 TI - Pastoral Group Counselling at a High Security Prison in Israel: Integrating Pierre Janet's Psychological Analysis with Fritz Perls' Gestalt Therapy. AB - This is a report of a short-term, pastoral counselling group conducted with Jewish internees in a high security prison in Israel. It was held as an adjunct to daily secular individual and group counselling and rehabilitation run by the Department of Social Work. Pastoral counselling employed spiritual and psychosocial methodologies to reduce anger, improve prisoner frustration tolerance, and develop a sense of self-efficacy and communal identity. It combined semi-didactic scriptural input with Pierre Janet's personality model, Fritz Perls' gestalt therapy, and analysis of the group process. PMID- 26162208 TI - Three Marys. PMID- 26162209 TI - In the Media. PMID- 26162214 TI - Varieties of (Scientific) Creativity: A Hierarchical Model of Domain-Specific Disposition, Development, and Achievement. AB - Prior research supports the inference that scientific disciplines can be ordered into a hierarchy ranging from the "hard" natural sciences to the "soft" social sciences. This ordering corresponds with such objective criteria as disciplinary consensus, knowledge obsolescence rate, anticipation frequency, theories-to-laws ratio, lecture disfluency, and age at recognition. It is then argued that this hierarchy can be extrapolated to encompass the humanities and arts and interpolated within specific domains to accommodate contrasts in subdomains (e.g., revolutionary versus normal science). This expanded and more finely differentiated hierarchy is then shown to have a partial psychological basis in terms of dispositional traits (e.g., psychopathology) and developmental experiences (e.g., family background). This demonstration then leads to three hypotheses about how a creator's domain-specific impact depends on his or her disposition and development: the domain-progressive, domain-typical, and domain regressive creator hypotheses. Studies published thus far lend the most support to the domain-regressive creator hypothesis. In particular, major contributors to a domain are more likely to have dispositional traits and developmental experiences most similar to those that prevail in a domain lower in the disciplinary hierarchy. However, some complications to this generalization suggest the need for more research on the proposed hierarchical model. PMID- 26162215 TI - Is One Dimension Enough? A Response to Simonton's Varieties of (Scientific) Creativity (2009). AB - We admire Simonton's valiant attempt to bring all of creativity under a single dimension. We offer a view that is sometimes complementary and sometimes distinct from Simonton's model: Our own multidimensional amusement park theoretical model, which tries to integrate domain-specific and domain-general points of view. We eagerly await future research on Simonton's model and are curious of how his hard soft dimension can be included into the creativity pantheon. PMID- 26162216 TI - Sources of Scientific Innovation: A Meta-Analytic Approach (Commentary on Simonton, 2009). AB - Innovations in science can be divided into at least four major types: radical revolutions (such as Copernican and Darwinian theory), technical revolutions (led by scientists such as Newton, Lavoisier, and Einstein), controversial innovations (for example, Semmelweis's theory of puerperal fever), and conservative innovations (eugenics and various vitalistic doctrines). Biographical predictors of support for scientific innovations are distinctly different depending on the type of innovation, as are the predictors of who initially engineers such innovations. A meta-analytic approach assessing each new scientific theory according to its salient features (including epistemological, ideological, and technical attributes) is required to make sense out of the varied predisposing factors associated with the origins of these innovations. These predisposing factors are not neatly classifiable in terms of Simonton's (2009, this issue) hierarchical model of domain-specific dispositions, although this model is applicable under some conditions. Instead, the principal sources of scientific achievement are largely a product of person-by-situation interaction effects that are dictated by the nature of the particular innovation. PMID- 26162217 TI - The Psychology of Simonton's Science: Commentary on Simonton (2009). AB - One key assumption of the psychology of science is that psychological factors make certain interests, talents, and abilities more likely and others less likely (Feist, 2006). The line of argument that Simonton (2009, this issue) puts forth integrating and uniting the meta-literatures on dispositional and developmental influences on scientific and artistic creativity-is not only consistent with this assumption from the psychology of science, but it is also a breeding ground for a host of testable hypotheses and calls for future empirical investigations. Given Simonton's own extraordinary levels of scientific creativity, indeed it would be interesting to turn his ideas back on him to see how his science is a product of his own developmental and dispositional experiences. We'll leave that, however, for future biographers and psychologists of science. PMID- 26162218 TI - Simplifying Theories of Creativity and Revisiting the Criterion Problem: A Comment on Simonton's (2009) Hierarchical Model of Domain-Specific Disposition, Development, and Achievement. AB - Simonton's (2009, this issue) hierarchical model represents a useful contribution to studies of creativity and eminence. Simonton breaks all kinds of new ground by extrapolating the hierarchy to the arts and humanities, interpolating it within disciplines, and relating it to family background and disposition. This commentary poses a few questions about the hierarchical model and proposes an alternative. I also introduce a candidate for a simple theory of creativity that focuses on a universally shared capacity. This simple theory complements Simonton's hierarchical view, though his applies best to actual performance and the simple theory of creativity applies to creative potential. PMID- 26162219 TI - Varieties of Perspectives on Creativity: Reply to Commentators. AB - In this reply, I concentrate on two broad issues raised by the four commentaries in this issue: the hierarchical model of domains and individual differences in creativity. In the first case, I cite additional research to address the contrast between "hard" and "soft" domains and the application of this contrast to children, adolescents, and noneminent adults. In the second case, I introduce two recent studies to confirm the model's predictions regarding personal creative achievement. I hope that the original article, the commentaries, and this reply will inspire future inquiries into creativity in all its disciplinary varieties. PMID- 26162220 TI - On Being Rejected: A Meta-Analysis of Experimental Research on Rejection. AB - This article presents the first meta-analysis of experimental research on rejection, sampling 88 studies. The results are consistent with a needs account, which states that rejection frustrates basic psychological needs, but not with a numbness account, which states that rejection causes physical and emotional numbness. Rejection moderately lowers mood (d = -0.50) and self-esteem (d = 0.70), but does not decrease arousal or flatten affect. Both belonging (d = 0.69) and control (d = 1.16) are frustrated by rejection. Aggressive responses to rejection, considered paradoxical by some, appear to be due to attempts to gain control; measures that contrast belonging and control (d = -1.17) cause antisocial responding, whereas measures that do not allow for control to be restored cause prosocial responding (d = 1.21). These findings suggest that rejection makes individuals feel bad-ready to act to restore control or belonging and that they will prioritize restoring control even if it requires being antisocial. PMID- 26162221 TI - Social Rejection, Control, Numbness, and Emotion: How Not To Be Fooled by Gerber and Wheeler (2009). AB - Emotional numbness remains an empirically supported and theoretically intriguing pattern of response to social exclusion that warrants further research, and it would be a loss to the field if such research were prematurely terminated or hampered by the unwarranted conclusions from misleading meta-analyses. The meta analyses by Gerber and Wheeler (2009, this issue) are based on a biased sample that omits much relevant work. Worse, the authors misinterpret what evidence they do assemble, even interpreting strong evidence for numbness as if it contradicted numbness. Their conclusions about control are similarly unfounded and misguided. PMID- 26162222 TI - Rejoinder to Baumeister, DeWall, and Vohs (2009). PMID- 26162223 TI - Shared Reality: Experiencing Commonality With Others' Inner States About the World. AB - Humans have a fundamental need to experience a shared reality with others. We present a new conceptualization of shared reality based on four conditions. We posit (a) that shared reality involves a (subjectively perceived) commonality of individuals' inner states (not just observable behaviors); (b) that shared reality is about some target referent; (c) that for a shared reality to occur, the commonality of inner states must be appropriately motivated; and (d) that shared reality involves the experience of a successful connection to other people's inner states. In reviewing relevant evidence, we emphasize research on the saying-is-believing effect, which illustrates the creation of shared reality in interpersonal communication. We discuss why shared reality provides a better explanation of the findings from saying-is-believing studies than do other formulations. Finally, we examine relations between our conceptualization of shared reality and related constructs (including empathy, perspective taking, theory of mind, common ground, embodied synchrony, and socially distributed knowledge) and indicate how our approach may promote a comprehensive and differentiated understanding of social-sharing phenomena. PMID- 26162225 TI - Erratum. PMID- 26162224 TI - Giving Psychological Science Away: The Role of Applications Courses. AB - The applicability of basic research in psychological science is obvious to those in the field, but too often underappreciated outside of it. In this article, I suggest some reasons for that gap, including confusion between the relevance of psychological science and its actual application, which can lead to hype; the interdisciplinary nature of applied science, which can obscure the credit due to the field; and the considerable difficulty of moving basic research into application, including the potential for resistance to the products we deliver. I suggest that our own students constitute a relatively underutilized audience for demonstrating that psychological science has been critical to applications, and I describe an applied cognitive science course that is intended to make the case to them. PMID- 26162226 TI - Glenohumeral translations during range-of-motion movements, activities of daily living, and sports activities in healthy participants. AB - BACKGROUND: Glenohumeral translations have been mainly investigated during static poses while shoulder rehabilitation exercises, activities of daily living, and sports activities are dynamic. Our objective was to assess glenohumeral translations during shoulder rehabilitation exercises, activities of daily living, and sports activities to provide a preliminary analysis of glenohumeral arthrokinematics in a broad range of dynamic tasks. METHODS: Glenohumeral translations were computed from trajectories of markers fitted to intracortical pins inserted into the scapula and the humerus. Two participants (P1 and P2) performed full range-of-motion movements including maximum arm elevations and internal-external rotations rehabilitation exercises, six activities of daily living, and five sports activities. FINDINGS: During range-of-motion movements, maximum upward translation was 7.5mm (P1) and 4.7mm (P2). Upward translation during elevations was smaller with the arm internally (3.6mm (P1) and 2.9mm (P2)) than neutrally (4.2mm (P1) and 3.7mm (P2)) and externally rotated (4.3mm (P1) and 4.3mm (P2)). For activities of daily living and sports activities, only anterior translation during reach axilla for P1 and upward translation during ball throwing for P2 were larger than the translation measured during range-of-motion movements (108% and 114%, respectively). INTERPRETATION: While previous electromyography-based studies recommended external rotation during arm elevation to minimize upward translation, measures of glenohumeral translations suggest that internal rotation may be better. Similar amplitude of translation during ROM movement and sports activities suggests that large excursions of the humeral head may be caused not only by fast movements, but also by large amplitude movements. PMID- 26162227 TI - The relationship between interruption content and interrupted task severity in intensive care nursing: an observational study. AB - BACKGROUND: In a previous study, we observed that the majority of interruptions experienced by nurses in a cardiovascular intensive care unit (CVICU) carried information directly related to their patient or other aspects of work affecting other patients or indirectly affecting their patient. Further, the proportion of interruptions with personal content was significantly higher during low-severity (in case of an error as defined by nurses) tasks compared to medium- and high severity tasks suggesting that other personnel may have evaluated the criticality of the nurses' tasks before interrupting. However, this earlier study only collected data when an interruption happened and thus could not investigate interruption rate as a function of primary task type and severity while controlling for primary task duration as an exposure variable. OBJECTIVES: We addressed this methodological limitation in a second observational study that was conducted to further study interruptions and also to evaluate an interruption mitigation tool. The data from the baseline condition (i.e., no tool) is analyzed in this paper to validate the results of our previous study and to report interruption rates observed during tasks of varying severities (low, medium, high), with a particular focus on comparing different interruption contents. DESIGN AND SETTING: The study was conducted in a 24-bed closed CVICU at a Canadian hospital, during day shifts. PARTICIPANTS: The baseline condition involved thirteen nurses. METHODS: Over a 3-week period, three researchers observed these nurses 46-120 min each, with an average of 89 min. Data were collected in real time, using a tablet computer and software designed for this purpose. The rate of interruptions with different content was compared across varying task severity levels as defined by CVICU nurses. RESULTS: Nurses spent about 50% of their time conducting medium-severity tasks (e.g., documentation), 35% conducting high-severity tasks (e.g., procedure), and 14% conducting low severity tasks (e.g., general care). The rate of interruptions with personal content observed during low-severity tasks was 1.97 (95% confidence interval, CI: 1.04, 3.74) and 3.23 (95% CI: 1.51, 6.89) times the rate of interruptions with personal content observed during high- and medium-severity tasks, respectively. CONCLUSIONS: Interrupters might have evaluated task severity before interrupting. Increasing the transparency of the nature and severity of the task being performed may help others further modulate when and how they interrupt a nurse. Overall, rather than try to eliminate all interruptions, mitigation strategies should consider the relevance of interruptions to a task or patient as well as their urgency. PMID- 26162228 TI - Nurses' blame attributions towards different types of cancer: A cross-sectional study. AB - BACKGROUND: Public health education increasingly emphasizes the link of personal lifestyle with cancer risk, which may result in unintended negative social effects such as triggering stigma and/or blame towards cancer patients when their illness is perceived to be caused by personal behaviours or disapproved lifestyles. OBJECTIVES: To explore nurses' blame attributions towards patients with different types of cancer and to identify associated factors. DESIGN: Cross sectional survey. SETTING: A tertiary cancer-specialized hospital in Beijing. PARTICIPANTS: 317 Chinese oncology nurses working in the cancer hospital. METHODS: Participant nurses completed a self-administrated anonymous questionnaire and rated how much they would blame someone with a diagnosis of breast cancer, cervical cancer, colon cancer, liver cancer, lung cancer, as well as leukaemia and obesity. RESULTS: More than half of the oncology nurses (57.1%) attributed at least some blame to patients with leukaemia, following with breast cancer (67.5%), cervical cancer (79.2%), liver cancer (79.2%), and colon cancer (78.5%). Lung cancer patients attracted at least some blame by 82.0% of participating nurses. Attributions of blame for patients with lung, cervical, colon and liver cancer were most common among nurses with shorter working experience. CONCLUSIONS: This study demonstrated that a high proportion of Chinese nurses attributed at least some blame to patients with different cancers despite being working in a cancer-specialized hospital. Future education and support for nurses are essential to avoid negative attitudes and blame attributions to cancer patients in order to enhance the quality of care. PMID- 26162229 TI - Metacarpophalangeal Arthroplasty for Osteoarthritis. PMID- 26162230 TI - Triceps Tendon Repair. AB - Complete triceps tendon rupture is relatively rare, but more commonly seen in the athletic population. Loss of extension strength is the functional deficit for the elbow after rupture of the triceps tendon. Although partial tears may be treated conservatively, complete tears of the triceps tendon must be repaired to provide active extension at the elbow. Our preferred surgical technique for repair of the acute triceps tendon rupture is presented, as well as strategies for reconstruction of the triceps tendon with an Achilles tendon allograft. PMID- 26162231 TI - Fixation and Grafting After Limited Debridement of Scaphoid Nonunions. AB - PURPOSE: To evaluate a surgical technique of treating nondisplaced waist and proximal pole scaphoid nonunions without avascular necrosis (AVN). METHODS: We performed a retrospective review of all patients with nondisplaced, scaphoid waist or proximal pole nonunions without AVN treated with the following technique. Two K-wires are positioned along the scaphoid axis to stabilize the proximal and distal poles. Debridement with a curette or burr is performed parallel to the nonunion site until the K-wires are visualized and punctate bleeding of the proximal and distal fragments is encountered. The volar, radial fibrous union is left intact. Distal radius cancellous bone graft is packed into the nonunion site. A headless screw is placed perpendicular to the fracture and the K-wires are removed. RESULTS: Between 2012 and 2014, 12 patients (ages 13-29 y) with clinical and radiographic evidence (10 had computed tomography or magnetic resonance imaging; 2 had radiographs only) of scaphoid nonunion were identified (10 transverse waist and 2 proximal pole fractures). Median interval from injury to surgery was 38 weeks (range, 3 mo to 9 y). Four patients were active smokers and 2 had failed previous iliac crest bone grafting. All patients healed as confirmed by computed tomography. Average time to union was 14 weeks (range, 6-31 wk). Four patients had delayed union requiring a bone stimulator. All patients had resolution of pain and there were no complications. CONCLUSIONS: The technique described is an effective and efficient method of treating nondisplaced scaphoid nonunions without AVN. We suggest that complete debridement of the nonunion is not essential to achieve union. In addition, pinning the proximal and distal scaphoid poles initially and maintaining the volar fibrous union of the scaphoid nonunion stabilizes the fracture fragments, increasing the technical ease of grafting and fixation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26162232 TI - Longitudinal Evaluation of Sympathetic Nervous System and Perfusion in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic Single-Photon Emission Computed Tomography. AB - The objective of this work was to evaluate the sympathetic nervous system and structure remodeling during the progression of heart failure in a rodent model using dynamic cardiac single-photon emission computed tomography (SPECT). The spontaneously hypertensive rat (SHR) model was used to study changes in the nervous system innervation and perfusion in the left ventricular (LV) myocardium with the progression of left ventricular hypertrophy (LVH) to heart failure. Longitudinal dynamic SPECT studies were performed with seven SHR and seven Wistar Kyoto (WKY) rats over 1.5 years using a dual-head SPECT scanner with pinhole collimators. Time-activity curves (TACs) of the 123I-MIBG and 201Tl distribution in the LV blood pool and myocardium were extracted from dynamic SPECT data and fitted to compartment models to determine the influx rate, washout rate, and distribution volume (DV) of 123I-MIBG and 201Tl in the LV myocardium. The standardized uptake values (SUVs) of 123I-MIBG and 201Tl in the LV myocardium were also calculated from the static reconstructed images. The influx and washout rates of 123I-MIBG did not show a significant difference between SHRs and WKY rats. The DVs of 123I-MIBG were greater in the SHRs than in the WKY rats (p = .0028). Specifically, the DV of 123I-MIBG became greater in the SHRs by 6 months of age (p = .0017) and was still significant at the age of 22 months. The SUV of 123I-MIBG in SHRs exhibited abnormal values compared to WKY rats from the age of 18 months. There was no difference in the influx rate and the washout rate of 201Tl between the SHRs and WKY rats. The SHRs exhibited greater DV of 201Tl than WKY rats after the age of 18 months (p = .034). The SUV of 201Tl in SHRs did not show any significant difference from WKY at all ages. The higher DV of 123I-MIBG in the LV myocardium reveals abnormal nervous system activity of the SHRs at an age of 6 months, whereas a greater DV of 201Tl in the LV myocardium can only be detected at an age of 18 months. The results show that the abnormal nervous system activity appears earlier than perfusion. Furthermore, the comparison between the DV and the SUV indicates that dynamic SPECT with 123I-MIBG and 201Tl with the kinetic parameter DV is capable of detecting abnormalities of the LV at an early age. PMID- 26162234 TI - Never Events in Surgery. AB - Never events such as wrong-site surgery are still somewhat prevalent in urology and may have serious adverse consequences for the patient, surgeon, and institution. By embracing a safety culture and improving mindfulness, urologists can minimize these events via system improvement. PMID- 26162233 TI - Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind. AB - PURPOSE: Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN: The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS: There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS: The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS: A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS: The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals. PMID- 26162235 TI - Accumulation and aggregate formation of mutant superoxide dismutase 1 in canine degenerative myelopathy. AB - Canine degenerative myelopathy (DM) is an adult-onset progressive neurodegenerative disorder that has recently been linked to mutations in the superoxide dismutase 1 (SOD1) gene. We generated a polyclonal antibody against canine SOD1 to further characterize the mutant SOD1 protein and its involvement in DM pathogenesis. This antibody (SYN3554) was highly specific to canine SOD1 and had the ability to reveal distinct cytoplasmic aggregates in cultured cells expressing canine mutant SOD1 and also in the spinal neurons of symptomatic homozygotes. A similar staining pattern was observed in asymptomatic homozygotes. SOD1 aggregates were not detected in the spinal neurons of heterozygotes; the accumulation of SOD1 was also detected in the reactive astrocytes of homozygotes and heterozygotes to a similar extent. Our results support the hypothesis that the cytoplasmic accumulation and aggregate formation of the mutant SOD1 protein, especially in astrocytes, are closely associated with the pathogenesis of DM. Therefore, this disease is regarded as a spontaneous large-animal model of SOD1 mediated amyotrophic lateral sclerosis in humans. PMID- 26162237 TI - Stargazing: Monitoring subcellular dynamics of brain astrocytes. AB - Astrocytes are major non-neuronal cell types in the central nervous system that regulate a variety of processes in the brain including synaptic transmission, neurometabolism, and cerebrovasculature tone. Recent discoveries have revealed that astrocytes perform very specialized and heterogeneous roles in brain homeostasis and function. Exactly how astrocytes fulfill such diverse roles in the brain remains to be fully understood and is an active area of research. In this review, we focus on the complex subcellular anatomical features of protoplasmic gray matter astrocytes in the mature, healthy brain that likely empower these cells with the ability to detect and respond to changes in neuronal and synaptic activity. In particular, we discuss how intricate processes on astrocytes allow these cells to communicate with neurons and their synapses and strategically deliver specific cellular organelles such as mitochondria and ribosomes to active compartments within the neuropil. Understanding the properties of these structural elements will lead to a better understanding of how astrocytes function in the healthy and diseased brain. PMID- 26162238 TI - Effects of short-term training on behavioral learning and skill acquisition during intraoral fine motor task. AB - Sensory information from the orofacial mechanoreceptors are used by the nervous system to optimize the positioning of food, determine the force levels, and force vectors involved in biting of food morsels. Moreover, practice resulting from repetition could be a key to learning and acquiring a motor skill. Hence, the aim of the experiment was to test the hypothesis that repeated splitting of a food morsel during a short-term training with an oral fine motor task would result in increased performance and optimization of jaw movements, in terms of reduction in duration of various phases of the jaw movements. Thirty healthy volunteers were asked to intraorally manipulate and split a chocolate candy, into two equal halves. The participants performed three series (with 10 trials) of the task before and after a short-term (approximately 30 min) training. The accuracy of the split and vertical jaw movement during the task were recorded. The precision of task performance improved significantly after training (22% mean deviation from ideal split after vs. 31% before; P<0.001). There was a significant decrease in the total duration of jaw movements during the task after the training (1.21 s total duration after vs. 1.56 s before; P<0.001). Further, when the jaw movements were divided into different phases, the jaw opening phase and contact phase were significantly shorter after training than before training (P=0.001, P=0.002). The results indicate that short-term training of an oral fine motor task induces behavior learning, skill acquisition and optimization of jaw movements in terms of better performance and reduction in the duration of jaw movements, during the task. The finding of the present study provides insights into how humans learn oral motor behaviors or the kind of adaptation that takes place after a successful prosthetic rehabilitation. PMID- 26162236 TI - Ultrastructural evidence for synaptic contacts between cortical noradrenergic afferents and endocannabinoid-synthesizing post-synaptic neurons. AB - Endocannabinoids (eCBs) are involved in a myriad of physiological processes that are mediated through the activation of cannabinoid receptors, which are ubiquitously distributed within the nervous system. One neurochemical target at which cannabinoids interact to have global effects on behavior is brain noradrenergic circuitry. We, and others, have previously shown that CB type 1 receptors (CB1r) are positioned to pre-synaptically modulate norepinephrine (NE) release in the rat frontal cortex (FC). Diacylglycerol lipase (DGL) is a key enzyme in the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). While DGL-alpha is expressed in the FC in the rat brain, it is not known whether noradrenergic afferents target neurons expressing synthesizing enzymes for the endocannabinoid, 2-AG. In the present study, we employed high-resolution neuroanatomical approaches to better define cellular sites for interactions between noradrenergic afferents and FC neurons expressing DGL-alpha. Immunofluorescence microscopy showed close appositions between processes containing the norepinephrine transporter (NET) or dopamine-beta-hydroxylase (DbetaH) and cortical neurons expressing DGL-alpha-immunoreactivity. Ultrastructural analysis using immunogold-silver labeling for DGL-alpha and immunoperoxidase labeling for NET or DbetaH confirmed that NET-labeled axon terminals were directly apposed to FC somata and dendritic processes that exhibited DGL-alpha-immunoreactivity. Finally, tissue sections were processed for immunohistochemical detection of DGL-alpha, CB1r and DbetaH. Triple label immunofluorescence revealed that CB1r and DbetaH were co-localized in common cellular profiles and these were in close association with DGL-alpha. Taken together, these data provide anatomical evidence for direct synaptic associations between noradrenergic afferents and cortical neurons exhibiting endocannabinoid synthesizing machinery. PMID- 26162239 TI - Adult attachment style modulates neural responses in a mentalizing task. AB - Adult attachment style (AAS) is a personality trait that affects social cognition. Behavioral data suggest that AAS influences mentalizing proficiency, i.e. the ability to predict and explain people's behavior with reference to mental states, but the neural correlates are unknown. We here tested how the AAS dimensions "avoidance" (AV) and "anxiety" (ANX) modulate neural correlates of mentalizing. We measured brain activation using functional magnetic resonance imaging (fMRI) in 164 healthy subjects during an interactive mentalizing paradigm (Prisoner's Dilemma Game). AAS was assessed with the Relationship Scales Questionnaire, including the subscales AV and ANX. Our task elicited a strong activation of the mentalizing network, including bilateral precuneus, (anterior, middle, and posterior) cingulate cortices, temporal poles, inferior frontal gyri (IFG), temporoparietal junctions, superior medial frontal gyri as well as right medial orbital frontal gyrus, superior temporal gyrus, middle frontal gyrus (MFG), and amygdala. We found that AV is positively and ANX negatively correlated with task-associated neural activity in the right amygdala, MFG, midcingulate cortex, and superior parietal lobule, and in bilateral IFG. These data suggest that avoidantly attached adults activate brain areas implicated in emotion regulation and cognitive control to a larger extent than anxiously attached individuals during mentalizing. PMID- 26162241 TI - Status epilepticus results in persistent overproduction of reactive oxygen species, inhibition of which is neuroprotective. AB - Epilepsy and seizure activity result in the generation of reactive oxygen species (ROS), which contribute to seizure-induced neuronal damage. Recent in vitro evidence indicates that NADPH oxidase contributes significantly to seizure induced ROS. We further tested this in rat glio-neuronal cultures and in ex vivo chronic epileptic rat brain tissue using live cell-imaging techniques. Here, we show that ROS are upregulated in chronic epilepsy and that ROS production contributes to cell death, which is seen after status epilepticus (SE) and chronic seizures. Inhibition of ROS production by AEBSF, a NADPH oxidase inhibitor, markedly reduced seizure-induced cell death in the perforant path model of epilepsy. These findings demonstrate a critical role for ROS, generated by NADPH oxidase, contributing to seizure-induced cell death. These findings point to NADPH oxidase inhibition as a novel treatment strategy to prevent brain injury in SE and chronic epilepsy. PMID- 26162240 TI - Effects of acoustic trauma on the auditory system of the rat: The role of microglia. AB - Exposure to loud, prolonged sounds (acoustic trauma, AT) leads to the death of both inner and outer hair cells (IHCs and OHCs), death of neurons of the spiral ganglion and degeneration of the auditory nerve. The auditory nerve (8cn) projects to the three subdivisions of the cochlear nuclei (CN), the dorsal cochlear nucleus (DC) and the anterior (VCA) and posterior (VCP) subdivisions of the ventral cochlear nucleus (VCN). There is both anatomical and physiological evidence for plastic reorganization in the denervated CN after AT. Anatomical findings show axonal sprouting and synaptogenesis; physiologically there is an increase in spontaneous activity suggesting reorganization of circuitry. The mechanisms underlying this plasticity are not understood. Recent data suggest that activated microglia may have a role in facilitating plastic reorganization in addition to removing trauma-induced debris. In order to investigate the roles of activated microglia in the CN subsequent to AT we exposed animals to bilateral noise sufficient to cause massive hair cell death. We studied four groups of animals at different survival times: 30 days, 60 days, 6 months and 9 months. We used silver staining to examine the time course and pattern of auditory nerve degeneration, and immunohistochemistry to label activated microglia in the denervated CN. We found both degenerating auditory nerve fibers and activated microglia in the CN at 30 and 60 days and 6 months after AT. There was close geographic overlap between the degenerating fibers and activated microglia, consistent with a scavenger role for activated microglia. At the longest survival time, there were still silver-stained fibers but very little staining of activated microglia in overlapping regions. There were, however, activated microglia in the surrounding brainstem and cerebellar white matter. PMID- 26162242 TI - Expression, purification and functional characterization of human equilibrative nucleoside transporter subtype-1 (hENT1) protein from Sf9 insect cells. AB - Human equilibrative nucleoside transporter-1 (hENT1) is the major plasma membrane transporter involved in transportation of natural nucleosides as well as nucleoside analog drugs, used in anti-cancer and anti-viral therapies. Despite extensive biochemical and pharmacological studies, little is known about the structure-function relationship of this protein. The major obstacles to purification include a low endogenous expression level, the lack of an efficient expression and purification protocol, and the hydrophobic nature of the protein. Here, we report protein expression, purification and functional characterization of hENT1 from Sf9 insect cells. hENT1 expressed by Sf9 cells is functionally active as demonstrated by saturation binding with a Kd of 1.2+/-0.2nM and Bmax of 110+/-5pmol/mg for [(3)H]nitrobenzylmercaptopurine ribonucleoside ([(3)H]NBMPR). We also demonstrate purification of hENT1 using FLAG antibody affinity resin in lauryl maltose neopentyl glycol detergent with a Kd of 4.3+/-0.7nM. The yield of hENT1 from Sf9 cells was ~0.5mg active transporter per liter of culture. The purified protein is functionally active, stable, homogenous and appropriate for further biophysical and structural studies. PMID- 26162243 TI - Enteric Viral Surrogate Reduction by Chitosan. AB - Enteric viruses are a major problem in the food industry, especially as human noroviruses are the leading cause of nonbacterial gastroenteritis. Chitosan is known to be effective against some enteric viral surrogates, but more detailed studies are needed to determine the precise application variables. The main objective of this work was to determine the effect of increasing chitosan concentration (0.7-1.5% w/v) on the cultivable enteric viral surrogates, feline calicivirus (FCV-F9), murine norovirus (MNV-1), and bacteriophages (MS2 and phiX174) at 37 degrees C. Two chitosans (53 and 222 kDa) were dissolved in water (53 kDa) or 1% acetic acid (222 KDa) at 0.7-1.5%, and were then mixed with each virus to obtain a titer of ~5 log plaque-forming units (PFU)/mL. These mixtures were incubated for 3 h at 37 degrees C. Controls included untreated viruses in phosphate-buffered saline and viruses were enumerated by plaque assays. The 53 kDa chitosan at the concentrations tested reduced FCV-F9, MNV-1, MS2, and phi X174 by 2.6-2.9, 0.1-0.4, 2.6-2.8, and 0.7-0.9 log PFU/mL, respectively, while reduction by 222 kDa chitosan was 2.2-2.4, 0.8-1.0, 2.6-5.2, and 0.5-0.8 log PFU/mL, respectively. The 222 kDa chitosan at 1 and 0.7% w/v in acetic acid (pH 4.5) caused the greatest reductions of MS2 by 5.2 logs and 2.6 logs, respectively. Overall, chitosan treatments showed the greatest reduction of MS2, followed by FCV-F9, phi X174, and MNV-1. These two chitosans may contribute to the reduction of enteric viruses at the concentrations tested but would require use of other hurdles to eliminate food borne viruses. PMID- 26162244 TI - The Usefulness of the Canadian Diabetes Risk Assessment Questionnaire (CANRISK) in Predicting Dysglycemia in Women with Histories of Gestational Diabetes. AB - OBJECTIVES: In Canada, approximately 20% of women with gestational diabetes (GDM) are diagnosed with type 2 diabetes by 9 years postpartum; therefore, regular screening for type 2 diabetes is recommended. Diabetes risk assessment questionnaires, such as the Canadian Diabetes Risk Assessment Questionnaire (CANRISK), may be used to inform screening strategies. However, CANRISK was developed to estimate personal diabetes risk for individuals >40 years old. Many postpartum women with GDM are <40 years old at the time of screening, so the utility of CANRISK in this population has not been established. The study sought to determine whether CANRISK accurately classifies women with histories of GDM in the appropriate 10-year risk categories for developing type 2 diabetes and whether it is equally useful in classifying dysglycemia in those women by age (i.e. <40 and >40 years). METHODS: A retrospective analysis was made of a cohort of Canadian women with GDM who were followed for 8 to 10 years postpartum. Women with oral glucose tolerance test results at the study's end were included, and had CANRISK scores calculated. Measures of diagnostic accuracy for CANRISK were calculated by dysglycemia status using the oral glucose tolerance test as the gold standard. RESULTS: Included in the study were 74 women. In women <40 years old, 17% with dysglycemia were missed, and 79% without dysglycemia had unnecessary laboratory testing. In women >40 years old, the CANRISK correctly classified 26 of 28 (92.9%) as being at "moderate" to "very high risk" for dysglycemia, thereby requiring further laboratory testing (p=0.03). CONCLUSIONS: CANRISK was not clinically useful in women <40 years old and was moderately useful in women >40 years old. PMID- 26162245 TI - Evaluating the microbicidal, antiparasitic and antitumor effects of CR-LAAO from Calloselasma rhodostoma venom. AB - CR-LAAO is an L-amino acid oxidase from Calloselasma rhodostoma snake venom that has been broadly studied regarding its structural and biochemical characteristics, however, few studies have investigated its pharmacological effects. The present study aimed at the evaluation of the biotechnological potential of CR-LAAO by determining its bactericidal, antifungal, leishmanicidal and trypanocidal activity, as well as its cytotoxicity on human tumor and non tumor cell lines. After 24 h of preincubation, CR-LAAO showed bactericidal effects against both Staphylococcus aureus (MIC 0.78 MUg/mL) and Escherichia coli (MIC 31.25 MUg/mL) strains, inducing dismantle of bacterial cell walls. After 6 h of preincubation with Candida albicans, CR-LAAO was able to inhibit 80% of the yeast growth, and it also showed cytotoxic activity on Leishmania species and Trypanosoma cruzi. Additionally, CR-LAAO showed high cytotoxicity on HepG2 and HL 60 tumor cells (IC50 10.78 and 1.7 MUg/mL), with lower effects on human mononuclear cells (PBMC). The cytotoxic effects of CR-LAAO were significantly inhibited in the presence of catalase, which suggests the involvement of hydrogen peroxide in its mechanisms of toxicity. Therefore, CR-LAAO showed promising pharmacological effects, and these results provide important information for the development of therapeutic strategies with directed action, such as more effective antimicrobial agents. PMID- 26162246 TI - Acid heteropolysaccharides with potent antileishmanial effects. AB - The present study investigated in vitro the effects of sulphated heterorhamnan (Go3), iota-/nu-carrageenans (G3d and EHW-I) and arabinogalactan (ARAGAL) polysaccharides on macrophage activation and inhibition of intracellular amastigotes of Leishmania (L.) amazonensis. All the sulphated polysaccharides (Go3, G3d and EHW-I) promoted increased nitric oxide production varying from 71 to 110%. The leishmanicidal activity of all compounds was compared to the inhibition effect of Meglumine Antimoniate at 300MUg/mL (~79%), used as positive control. Inhibition of Leishmania (L.) amazonensis growth was 55% with 5MUg/mL of Go3, 50% and 98% to G3d and EHW-I, respectively at 10MUg/mL, and 88% with 10MUg/mL of ARAGAL. The superoxide anion scavenging activity for the sulphated polysaccharides varied from approximately 30-55% at 10MUg/mL. In conclusion, the results of the present study indicate the promising potential of these polysaccharides for the development of new alternative therapeutic agents against leishmaniasis. PMID- 26162247 TI - Trends in Unmet Need for Genetic Counseling Among Children With Special Health Care Needs, 2001-2010. AB - OBJECTIVE: Access to genetic counseling is increasingly important to guide families' and clinicians' decision making, yet there is limited research on accessibility and affordability of counseling for families with children with special health care needs (CSHCN). Our study's objectives were to measure changes in unmet need for genetic counseling for CSHCN from 2001 to 2010 and to characterize child, family, and health system factors associated with unmet need. METHODS: We used parent-reported data from the 2001, 2005-2006, and 2009-2010 National Survey of Children With Special Health Care Needs. We used a logistic regression model to measure the impact of survey year, child (sex, age, severity of health condition), family (primary language, household income, insurance, financial problems related to cost of CSHCN's health care), and health system factors (region, genetic counselors per capita, having a usual source of care) on access to genetic counseling. RESULTS: Unmet need for genetic counseling increased significantly in 2009-2010 compared to 2001 (odds ratio 1.89; 95% confidence interval [CI] 1.44-2.47). Being older (adjusted odds ratio [aOR] 1.04; 95% CI 1.02-1.06), having severe health limitations (aOR 1.72; 95% CI 1.16-2.58), being uninsured (aOR 3.56; 95% CI 2.16-5.87), and having family financial problems due to health care costs (aOR 1.90; 95% CI 1.52-2.38) were significantly associated with greater unmet need for genetic counseling. Having a usual source of care was associated with decreased unmet need (aOR 0.55; 95% CI 0.37-0.83). CONCLUSIONS: Unmet need for genetic counseling has increased over the past 12 years. Uninsurance and financial problems related to health care costs were the largest drivers of unmet need over time. PMID- 26162248 TI - Are transversal MR images sufficient to distinguish persons with mild cognitive impairment from healthy controls? AB - RATIONALE AND OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This study aims to determine whether current standard magnetic resonance imaging (MRI) is providing markers that can distinguish between subjects with amnestic MCI (aMCI), nonamnestic MCI (naMCI), and healthy controls (HCs). MATERIALS AND METHODS: A subset of 126 MCI subjects and 126 age-, gender-, and education-appropriate HCs (mean age, 70.9 years) were recruited from 4157 participants in the longitudinal community-based Heinz Nixdorf Recall Study. The burden of white matter hyperintensities (WMHs), cerebral microbleeds, and brain atrophy was evaluated on transversal MR images from a single 1.5-T MR scanner by two blinded neuroradiologists. Logistic regression and receiver-operating characteristic analysis were used for statistical analysis. RESULTS: Occipital WMH burden was significantly increased in aMCI, but not in naMCI relative to HCs (P = .01). The combined MCI group showed brain atrophy relative to HCs (P = .01) pronounced at caudate nuclei (P = .01) and temporal horn level (P = .004) of aMCI patients and increased at the frontal and occipital horns of naMCI patients compared to either aMCI or HCs. Microbleeds were equally distributed in the MCI and control group, but more frequent in aMCI (22 of 84) compared to naMCI subjects (3 of 23). CONCLUSIONS: In his cohort, increased occipital WMHs and cortical and subcortical brain atrophies at temporal horn and caudate nuclei level distinguished aMCI from naMCI subjects and controls. Volumetric indices appear of interest and should be assessed under reproducible conditions to gain diagnostic accuracy. PMID- 26162249 TI - Validation of renal artery dimensions measured by magnetic resonance angiography in patients referred for renal sympathetic denervation. AB - RATIONALE AND OBJECTIVES: Magnetic resonance angiography (MRA) is a well established modality for the assessment of renal artery stenosis. Using dedicated quantitative analyses, MRA can become a useful tool for assessing renal artery dimensions in patients referred for renal sympathetic denervation (RDN) and for providing accurate measurements of vascular response after RDN. The purpose of this study was to test the reproducibility of a novel MRA quantitative imaging tool and to validate these measurements against intravascular ultrasound (IVUS). MATERIALS AND METHODS: In nine patients referred for renal denervation, renal artery dimensions were measured. Bland-Altman analysis was used to assess the intraobserver and interobserver reproducibility. RESULTS: Mean lumen diameter was 5.8 +/- 0.7 mm, with a very good intraobserver and interobserver variability of 0.7% (reproducibility: bias, 0 mm; standard deviation [SD], 0.1 mm) and 1.2% (bias, 0 mm; SD, 0.1 mm), respectively. Mean total lumen volume was 1035.3 +/- 403.6 mm(3) with good intraobserver and interobserver variability of 2.9% (bias, 9.7 mm(3); SD, 34.0 mm(3)) and 2.8% (bias, -11.4 mm(3); SD, 42.4 mm(3)). The correlation (Pearson R) between mean lumen diameter measured with MRA and IVUS was 0.750 (P = .002). CONCLUSIONS: Using a novel MRA quantitative imaging tool, renal artery dimensions can be measured with good reproducibility and accuracy. MRA-derived diameters and volumes correlated well with IVUS measurements. PMID- 26162250 TI - The Impact of Expasyl(r) Gingival Retraction Paste on the Bond Strength of Self etch and Total-etch Systems. AB - OBJECTIVE: To evaluate the influence of Expasyl(r) gingival retraction paste on the shear bond strength of self-etch and total-etch adhesive systems. MATERIALS AND METHODS: Twenty-four specimens of extracted, caries-free, sound human molars were used in this study. The molars were then cut vertically into halves through the buccal and lingual cusps. Forty-eight specimens were divided into four groups (total-etch, total-etch with Expasyl application, self-etch, self-etch with Expasyl application) and the shear bond strength was tested. RESULTS: Expasyl significantly reduced the shear bond strength of the self-etch and total-etch adhesive systems. The self-etch system showed relatively lower performance compared with the total-etch adhesive system. The shear bond strength values of the total-etch adhesive without Expasyl showed the highest bond strength (21.48 +/- 2.89), while the self-etching group adhesive treated with Expasyl showed the lowest shear bond strength value (14.89 +/- 1.81). CONCLUSION: From the observations of this in vitro study, it can be concluded that the use of Expasyl(r) gingival retraction system can negatively affect bond strength of adhesives. The total-etch system showed better compatibility to the Expasyl gingival retraction system than the self-etch. PMID- 26162251 TI - Antibacterial Potential of 2.5% Sodium Hypochlorite in Distinct Irrigation Protocols on Enterococcus faecalis Biofilm. AB - OBJECTIVE: The aim of this study was to evaluate the effect of irrigation methods on antibacterial potential of 2.5% NaOCl on Enterococcus faecalis biofilm. MATERIALS AND METHODS: Enterococcus faecalis biofilms were prepared during 60 days on 48 human root canals and randomized into control and experimental groups using positive and negative pressure irrigation. Bacterial growth was analyzed using turbidity of culture medium followed by UV spectrophotometry, and scanning electron microscopy (SEM) analyses were performed. Mean and standard deviations were used for evaluate the mean optical densities associated to the number of bacteria present culture, and Scheirer-Ray-Hare (an extension of the Kruskal Wallis test) and Tamhane test to analyze the SEM images in the groups and thirds. Significance was set at 5%. RESULTS: Enterococcus faecalis was still present after root canal cleaning regardless of irrigation methods or bacterial identification methods. CONCLUSION: Positive and negative pressure irrigation protocols using 2.5% NaOCl show a similar capacity to reduce E. faecalis in infected root canals. PMID- 26162252 TI - Effect of Different Thicknesses of Pressable Ceramic Veneers on Polymerization of Light-cured and Dual-cured Resin Cements. AB - AIM: This study evaluated the effects of ceramic veneer thicknesses on the polymerization of two different resin cements. MATERIALS AND METHODS: A total of 80 ceramic veneer disks were fabricated by using a pressable ceramic material (e.max Press; Ivoclar Vivadent) from a Low Translucency (LT) ingot (A1 shade). These disks were divided into light-cured (LC; NX3 Nexus LC; Kerr) and dual-cured (DC; NX3 Nexus DC; Kerr) and each group was further divided into four subgroups, based on ceramic disk thickness (0.3, 0.6, 0.9, and 1.2 mm). The values of Vickers microhardness (MH) and degree of conversion (DOC) were obtained for each specimen after a 24-hour storage period. Association between ceramic thickness, resin cement type, and light intensity readings (mW/cm(2)) with respect to microhardness and degree of conversion was statistically evaluated by using analysis of variance (ANOVA). RESULTS: For the DOC values, there was no significant difference observed among the LC resin cement subgroups, except in the 1.2 mm subgroup; only the DOC value (14.0 +/- 7.4%) of 1.2 mm DC resin cement had significantly difference from that value (28.9 +/- 7.5%) of 1.2 mm LC resin cement (p < 0.05). For the MH values between LC and DC resin cement groups, there was statistically significant difference (p < 0.05); overall, the MH values of LC resin cement groups demonstrated higher values than DC resin cement groups. On the other hands, among the DC resin cement subgroups, the MH values of 1.2 mm DC subgroup was significantly lower than the 0.3 mm and 0.6 mm subgroups (p < 0.05). However, among the LC subgroups, there was no statistically significant difference among them (p > 0.05). CONCLUSION: The degree of conversion and hardness of the resin cement was unaffected with veneering thicknesses between 0.3 and 0.9 mm. However, the DC resin cement group resulted in a significantly lower DOC and MH values for the 1.2 mm subgroup. CLINICAL SIGNIFICANCE: While clinically adequate polymerization of LC resin cement can be achieved with a maximum 1.2 mm of porcelain veneer restoration, the increase of curing time or light intensity is clinically needed for DC resin cements at the thickness of more than 0.9 mm. PMID- 26162253 TI - Correlation of Dental and Skeletal Malocclusions in Sagittal Plane among Saudi Orthodontic Patients. AB - AIM: Whether or not the dental relationship correlates with skeletal relationship in the sagittal plane is an area of interest for orthodontic diagnosis and treatment planning. Thus, the aim of this study was to investigate the correlation of the dental malocclusion and the skeletal malocclusion in the sagittal plane among Saudi orthodontic patients. MATERIALS AND METHODS: Orthodontic dental casts and cephalometric radiographs of 124 patients were investigated and analyzed. The dental casts were classified in relation to the molar relationship according to Angle's classification and to the incisal relationship according to the British Standards Institution (BSI) classification. The sagittal relation in the cephalometric radiographs was analyzed according to ANB angle and WITS appraisal. RESULTS: The results show that the incisal relation had a very high significant association with WITS appraisal (p = 0.0045), whereas with ANB, the association was marginally significant (p =0.0528). No significant associations were found with molar relation neither at ANB (p = 0.2075) nor at the WITS (p = 0.4794) appraisal. Significant positive correlations between ANB and WITS appraisal were found at the three incisal classification classes (class I, r = 0.73; class II, r = 0.64; class III, r = 0.75) and no significant correlation was observed in all classes with the Angle's (molar) classification. CONCLUSIONS: The incisal classification had a significant association with WITS appraisal, whereas with ANB the association was marginally significant. No correlation was found between Angle's (molar) classification and ANB or WITS appraisal. CLINICAL SIGNIFICANCE: The incisal relation could be considered as a good indicator of the skeletal malocclusion in the sagittal plane in the orthodontic practice. PMID- 26162254 TI - Comparison of Canal Transportation, Centering Ratio by Cone-beam Computed Tomography after Preparation with Different File Systems. AB - AIM: One Shape Apical 1 (OSA 1) is a new file for preparing the apical aspect of the root canal after One Shape (OS, Micro Mega, Besancon, France). This study compared apical transportation and centering ratios in curved root canals, which were instrumented with ProTaper Next (PTN, Dentsply Tulsa Dental Specialties, Tulsa, OK) up to size X3 and with OS up to OSA 1. MATERIALS AND METHODS: Forty eight mesial canals of mandibular molars were assigned into two groups (n = 24) with respect to canal length and curvature. Root canals were accessed conventionally and preperation was completed with PTN files up to X3 or with OS up to OSA 1 according to the manufacturer's protocols. Apical transportation was assessed pre- and postinstrumentation using cone-beam computed tomographic (CBCT) scans of 1, 2, 3, 4, and 5 mm sections. A Friedman test was performed to assess the significance between file systems. RESULTS: No significant difference was found between the file systems regarding apical transportation and centering ratio values (p > 0.05). Transportation in the mesial direction was greater than the distal transportation for both file systems. CONCLUSION: Considering apical transportation and centering ratio in curved canals, two systems provided similar results. CLINICAL SIGNIFICANCE: Preparation up to One Shape Apical 1 or ProTaper Next X3 was shown similar results regarding apical transportation and centering ratio. Both systems were safe to use in curved molar root canals. PMID- 26162255 TI - Evaluation of an Innovative Digital Assessment Tool in Dental Anatomy. AB - AIM: The E4D Compare software is an innovative tool that provides immediate feedback to students' projects and competencies. It should provide consistent scores even when different scanners are used which may have inherent subtle differences in calibration. This study aimed to evaluate potential discrepancies in evaluation using the E4D Compare software based on four different NEVO scanners in dental anatomy projects. Additionally, correlation between digital and visual scores was evaluated. MATERIALS AND METHODS: Thirty-five projects of maxillary left central incisors were evaluated. Among these, thirty wax-ups were performed by four operators and five consisted of standard dentoform teeth. Five scores were obtained for each project: one from an instructor that visually graded the project and from four different NEVO scanners. A faculty involved in teaching the dental anatomy course blindly scored the 35 projects. One operator scanned all projects to four NEVO scanners (D4D Technologies, Richardson, TX, USA). The images were aligned to the gold standard, and tolerance set at 0.3 mm to generate a score. The score reflected percentage match between the project and the gold standard. One-way ANOVA with repeated measures was used to determine whether there was a significant difference in scores among the four NEVO scanners. Paired-sample t-test was used to detect any difference between visual scores and the average scores of the four NEVO scanners. Pearson's correlation test was used to assess the relationship between visual and average scores of NEVO scanners. RESULTS: There was no significant difference in mean scores among four different NEVO scanners [F(3, 102) = 2.27, p = 0.0852 one-way ANOVA with repeated measures]. Moreover, the data provided strong evidence that a significant difference existed between visual and digital scores (p = 0.0217; a paired - sample t-test). Mean visual scores were significantly lower than digital scores (72.4 vs 75.1). Pearson's correlation coefficient of 0.85 indicated a strong correlation between visual and digital scores (p < 0.0001). CONCLUSION: The E4D Compare software provides consistent scores even when different scanners are used and correlates well with visual scores. CLINICAL SIGNIFICANCE: The use of innovative digital assessment tools in dental education is promising with the E4D Compare software correlating well with visual scores and providing consistent scores even when different scanners are used. PMID- 26162256 TI - Evaluation of Fracture Resistance of Orthodontic Mini-implants in the Transmucosal Profile Region. AB - AIM: This study sought to compare the fracture resistance of three trademarked orthodontic mini-implants in the transmucosal profile region. Thirty-six mini implants of three different brands, separated into groups I, II and III, were tested. Each group consisted of 12 mini-implants of 6 mm in length. The mean diameter and length of the transmucosal profile of the mini-implants were 1.90 and 2.0 mm in group I, 1.77 and 1.0 mm in group II and 1.50 and 1.0 mm in group III, respectively. The tests were performed on a universal testing machine in compression mode, with a 2,000 kgf load, a speed of 4.0 mm per minute and a chisel-shaped active tip, which acted cross-sectionally on the transmucosal profile. Single-criterion analysis of variance was used to compare the three brands. A significance level of 5% and test power of 80% were adopted. The mean fracture resistance achieved by the mini-implants was 172.03 +/- 25.59 N for group I, 162.35 +/- 30.81 N for group II and 139.69 +/- 42.99 N for group III. There was no statistically significant difference in mean fracture resistance among the tested mini-implant brands. CONCLUSION: The transmucosal profile diameter does not seem to be a deciding factor in the choice of mini-implants to minimize the risk of fractures. CLINICAL SIGNIFICANCE: Although being an in vitro study it is possible to believe that this new brand has a very satisfactory resistance to fracture and enables its use with great efficiency. PMID- 26162257 TI - The Effect of 3% Phosphate Ascorbyl Gel on Bond Strength of Composite Resin to Enamel treated with 35% Hydrogen Peroxide. AB - OBJECTIVE: To evaluate the effect of 3% phosphate ascorbyl gel (PA) in different times onto the microshear bond strength of composite resin (CR) to bovine enamel treated with 35% hydrogen peroxide (HP). MATERIALS AND METHODS: Thirty enamel blocks of bovine incisors were made and divided into 5 groups (n = 6) with three specimens per group (n = 18), according to treatment: G1= No bleaching + CR; G2 = HP + CR after 15d; G3 = HP + CR after 24 hours; G4 = HP + PA (15 min) + CR after 24 hours; G5 = HP + PA (2 hours) + CR after 24 hours. The resin cylinders were made by Tygon matrices. Microshear bond strength test was performed using universal testing machine with a 50N load at a speed of 0.5 mm/min. Fracture modes were assessed by a stereomicroscope 40 *. Microshear bond strength values were submitted to the analysis of variance (ANOVA) one-way and Tukey test (p < 0.05). RESULTS: G1 had significant results when compared to G3 and G5 (p < 0.01). However, G2, G3, G4 and G5 have showed no significant differences among groups (p > 0.05). Failure modes were categorized into adhesive (90%) and mixed (10%). CONCLUSION: The use of 3% phosphate ascorbyl gel for 15 minutes was able to improve bond strength of composite resin to bleached bovine enamel, but when 3% phosphate ascorbyl gel was applied during 40 minutes it negatively interfered in the adhesion of the resin to bleached bovine enamel. PMID- 26162258 TI - Employment of Reservoirs in At-Home Whitening Trays: Efficacy and Efficiency in Tooth Whitening. AB - AIM: This study aimed to determine the efficacy of trays made with and without reservoirs, in conjunction with time and cost evaluations, by measuring color change with home whitening procedures. MATERIALS AND METHODS: Extracted human maxillary teeth (central incisors n = 20; canines n = 20; molars n = 20) and 60 artificial teeth (lateral n = 20; premolar n = 40) were mounted into ten typodonts. Tray fabrication was completed such that a block-out resin reservoir was placed on half of the buccal surface of the tray, while the other half remained without a reservoir. Whitening with custom fabricated trays was performed based on two different whitening regimens, where each regimen was assigned to five typodonts: Night-time: Opalescence PF 10% carbamide peroxide for 8 hours daily and Day-time: Philips DayWhite 9.5% hydrogen peroxide for 30 minutes, twice daily. Both systems were applied for 1 week. To evaluate tooth shade, the VITA Easyshade(r) Advance 4.0 spectrophotometer was used. Color measurements were obtained at baseline (T1), 1-day post-whitening (T2), and 1 month post-whitening (T3). One-way ANOVA, followed by post-hoc Tukey's HSD test, was used to detect significant difference in the overall color change (DeltaE*) among the four groups at T2 and T3. Additionally, paired-sample t-test was used to assess difference in DeltaE* between T2 and T3 treatment within each of four techniques of tray fabrication. RESULTS: No significant difference in DeltaE* was found among the four groups at T2 and T3 (p > 0.05 in each instance). There were significant differences in mean DeltaE* between T2 and T3 treatment for the day white treatment groups without reservoir (6.96 vs 10.19 respectively; p = 0.0026) and with reservoirs (6.23 vs 9.79 respectively; p = 0.0031). CONCLUSION: The use of reservoirs does not have a significant effect on whitening efficacy, regardless of type of whitening material and regimen. CLINICAL SIGNIFICANCE: The use of custom fabricated trays with or without reservoirs were equally effective in whitening teeth. PMID- 26162259 TI - Lichenoid Features and Fibrosis: Coexistence in Quid-induced Oral Lesions. AB - BACKGROUND: Oral submucous fibrosis (OSF) and quid associated oral lichenoid lesions (QOLL) are caused because of areca nut chewing and both show very characteristic histological changes. The present study aims to determine the histopathological presence of lichenoid features in cases of OSF as well as to determine the presence of fibrosis in cases of QOLL. MATERIALS AND METHODS: The study involved the retrospective analysis of hematoxylin and eosin stained slides of OSF (n = 50) and QOLL (n = 16). RESULTS: Seven cases of OSF revealed histopathological features of lichenoid reaction and four cases of QOLL revealed the presence of fibrosis in the underlying connective tissue. CONCLUSION: This study put forths a new finding that is, the presence of concomitant disease processes seen in the same patient at a histological level. It thus, stresses the need to evaluate all cases of OSF and QOLL for additional features which may be induced by areca nut chewing. PMID- 26162260 TI - An in vitro Comparison of Endodontic Medicaments Propolis and Calcium Hydroxide alone and in Combination with Ciprofloxacin and Moxifloxacin against Enterococcus Faecalis. AB - AIM: To evaluate and compare the antimicrobial properties of propolis and calcium hydroxide alone and in combination with ciprofloxacin and moxifloxacin against Enterococcus faecalis (E. Faecalis). MATERIALS AND METHODS: The laboratory study was carried out to test the effectiveness of propolis and calcium hydroxidealone as well as in combination with the established endodontic medicaments (moxifloxacin and ciprofloxacin). The various combinations were-group 1: propolis, group 2: calcium hydroxide, group 3: moxifloxacin, group 4: ciprofoxacin, group 5: propolis + moxifloxacin, group 6: propolis + Ciprofloxacin, group 7: calcium hydroxide + ciprofloxacin, group 8: calcium hydroxide + moxifloxacin. The efficacy of these medicaments was tested by checking for the zone of inhibition for the specific strain (ATCC 29212) of E. faecalis at different time intervals, i.e. 24, 48 and 72 hours. RESULTS: Mean zone of inhibition was maximum in group V (21.94 +/- 4.26) followed by group VI (18.80 +/- 1.93), group I (18.71 +/- 4.26), group VIII (15.88 +/- 2.59), group III (14.91 +/- 1.00), group VII (14.57 +/- 2.17), group IV (13.91 +/- 1.00) and minimum in group II (12.89 +/- 2.14). Mean zone of inhibition was found to be maximum at 72 hours and minimum at 24 hours. At all time intervals, the combination of Propalis with Moxifocacin showed the maximum antimicrobial efficacy. CONCLUSION: On the basis of the results of the present study, it can be concluded that propolis and calcium hydroxide show synergistic effect with moxifloxacin and ciprofloxacin against E. Faecalis. Propolis in combination with antibiotics and alone is more effective than calcium hydroxide. CLINICAL SIGNIFICANCE: Since propolis alone and in combination with antibiotics was observed to be more effective than calcium hydroxide, propolis can be considered as an intracanal medicament when compared to traditional calcium hydroxide. PMID- 26162261 TI - Evaluation of the Effects of Dental Implants on Oral Lesions. AB - OBJECTIVE: To determine whether dental implants impress oral lesions, and to evaluate the nature of their effect on the lesions. MATERIALS AND METHODS: A comprehensive search was done via Google and PubMed for articles (including case reports and literature reviews) containing the keywords 'oral squamous cell carcinoma' (OSCC), 'oral lichen planus' (OLP), 'lichenoid contact reaction' (LCR), 'osseointegrated implants', and 'dental implants' , in the last 10 years (2002-2012). RESULTS: The study included 24 articles involving patients with dental implants, and some oral lesions (e.g. oral lichen planus and oral squamous cell carcinoma) or with a history of lesions. In these publications, there is evidence suggesting the possibility of emergence, exacerbation, recurrence, or even malignant transformation of the oral lesions after implant placement in some cases. CONCLUSION: Based on our review of the literature, implant treatment does not seem to be completely safe under any circumstances, but may have some complications in subjects with certain diseases (e.g. oral lesions, autoimmune diseases, malignancies, allergic reactions, etc.). Therefore prior to treatment, patients should be fully informed of the risks. CLINICAL SIGNIFICANCE: Implant treatment is best done with caution in patients with cancer or mucocutaneous disorders. PMID- 26162262 TI - Resilon: Review of a New Material for Obturation of the Canal. AB - Resilon is a thermoplastic synthetic polymer-based endodontic material alternative to gutta-percha. It contains bioactive glass and also radiopaque fillers. It has the same handling properties as gutta-percha. For endodontic retreatment, it may be dissolved with some solvents, such as chloroform or softened with heat. The composition of Resilon and its sealer (Epiphany) bond to dentin and form a monoblock. A review of the literature and a discussion of its properties comparing to other root canal filling materials are presented. PMID- 26162263 TI - Management of Impacted Maxillary Central Incisor: Modified Nance Arch Application. AB - This is a case report of a patient who presented to Wenzhou Medical University- Orthodontic Department at 8 years of age with missing right maxillary central incisor. A detailed clinical and radiographic examination was carried out and treatment plan formulated to surgically expose the impacted incisor and use the modified nance arch (MNA) appliance for orthodontic traction of the tooth in line of arch as phase one treatment followed by phase two treatment with fixed appliances. PMID- 26162264 TI - Interdental Implant Papillae Grow up with Temporary Abutment displaced at Monthly Intervals. AB - Interdental papillae regeneration remains a challenge in implant dentistry in cases in which papillae are lost following tooth extraction. This report presents an implant case with missing 1st and 2nd premolars and total papillary loss. We performed immediate provisionalization to the first premolar implant with a temporary abutment and crown, whereas the second premolar was submerged. Crown contouring and modifications to the shape and size were performed once every month (the temporary abutment and crown disconnected three times during the 3 month healing period). At the end of the 3-month healing period, papillae regeneration was observed between the implant and the adjacent tooth and between the adjacent implants. Papillae regeneration is possible with temporary abutment and a composite material crown that is properly contoured and polished, even with several abutment removals during the healing period. PMID- 26162265 TI - Unveiling the Molecular Signature of Salivary Gland Neoplasms with Tumor-specific Fusion Oncogenes. PMID- 26162266 TI - Reliability and effectiveness of percutaneous sacroplasty in sacral insufficiency fractures. AB - We evaluated the clinical results of sacroplasty for sacral insufficiency fracture (SIF). SIF are rare fractures that present as low back and groin pain. The diagnosis of SIF is difficult and sacroplasty is the last line of treatment. We reviewed the clinical and radiological data of 15 patients who underwent sacroplasty. Fifteen patients were selected, 12 women and three men, all of whom had failed to respond to medical therapy and bed rest, and were aged 39-76 years (mean 65.7). A retrospective electronic medical record review and face-to-face or phone interview was conducted. The patients' pain was assessed using the visual analogue scale (VAS) and functional status was assessed using the Oswestry disability index (ODI). Radiological diagnoses and investigations were performed using sacral CT scans and MRI. The sacroplasty procedures were performed using the short axis technique. The preoperative VAS scores (mean+/-standard deviation) were reduced from 7.6+/-0.7 to 1.7+/-0.7 postoperatively (p<0.05). The preoperative ODI was also reduced from an mean of 44 (range: 38-46) to 14 (11-22) postoperatively (p<0.05). Sacroplasty is an effective and safe procedure to relieve pain due to SIF. PMID- 26162267 TI - Divorcing physics from biology? Optimal foraging and Levy flights: Comment on "Liberating Levy walk research from the shackles of optimal foraging" by A.M. Reynolds. PMID- 26162268 TI - What future for Levy walks in animal movement research?: Comment on "Liberating Levy walk research from the shackles of optimal foraging", by A.M. Reynolds. PMID- 26162269 TI - Orthotropic heart transplantation for adult congenital heart disease: a case with heterotaxy and dextrocardia. AB - A 41-year-old male with heterotaxy (left isomerism) and dextrocardia composed by single ventricle, absent inferior vena cava, bilateral superior vena cava (SVC), common atrioventricular valve has received orthotopic heart transplantation (HTx) after long waiting period as Status-1. Reconstructions of bilateral SVC and hepatic vein route were successful without use of prosthetic material, and the donor heart was placed in the left mediastinum. In spite of satisfactory early recovery, the patient expired 4 months after transplantation mainly from fungal infection which developed following humoral rejection. HTx for adult patients with complex congenital heart disease is demanding in technical as well as pre- and post-transplant management, and indication should be critically determined. PMID- 26162270 TI - The prognostic value of plasma thrombospondin-1 concentrations after aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Thrombospondin-1 is a homotrimeric glycoprotein with well known functions in hemostasis and angiogenesis. Its expression was increased after experimental intracerebral hemorrhage. We determined whether increased plasma thrombospondin-1 concentrations are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Plasma thrombospondin-1 concentrations of 118 aSAH patients and 118 age- and gender-matched healthy controls were determined using enzyme-linked immunosorbent assay. Patients were followed up until death or completion of 6months after aSAH. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. Multivariate analyses of significant variables of univariate analyses were performed to determine independent risk factors for the clinical outcomes. RESULTS: Plasma thrombospondin-1 concentrations were significantly higher in aSAH patients than in healthy controls; plasma thrombospondin-1 concentrations were independently associated with clinical severity reflected by the World Federation of Neurological Surgeons score and Fisher score; thrombospondin-1 was identified as an independent predictor of 6-month mortality and 6-month unfavorable outcome; thrombospondin-1 had similar predictive performance compared with the World Federation of Neurological Surgeons score and Fisher score according to receiver operating characteristic curve analysis. CONCLUSION: Higher plasma thrombospondin 1 concentrations are associated with clinical severity and long-term prognosis of aSAH patients. PMID- 26162271 TI - MMPs and ADAMTSs in intervertebral disc degeneration. AB - Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with low back pain, a leading cause of musculoskeletal disability worldwide. The major components of extracellular matrix (ECM) within the discs are type II collagen (Col II) and aggrecan. Excessive destruction of ECM, especially loss of Col II and aggrecan, plays a critical role in promoting the occurrence and development of IDD. Matrix metalloproteinases (MMPs) and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTSs) are primary enzymes that degrade collagens and aggrecan. There is a large and growing body of evidence that many members of MMPs and ADAMTSs are highly expressed in degenerative IVD tissue and cells, and are closely involved in ECM breakdown and the process of disc degeneration. In contrast, targeting these enzymes has shown promise for promoting ECM repair and mitigating disc regeneration. In the current review, after a brief description regarding the biology of MMPs and ADAMTSs, we mainly focus on their expression profiles, roles and therapeutic potential in IDD. A greater understanding of the catabolic pathways involved in IDD will help to develop potential prophylactic or regenerative biological treatment for degenerative disc disease in the future. PMID- 26162272 TI - [Imaging for urinary incontinence]. AB - BACKGROUND: Ultrasonography and functional cine magnetic resonance imaging (MRI) are noninvasive and x-ray free tools, which are currently widely used in clinical diagnostics and scientific research of male and female urinary incontinence. The increasing use and improving techniques of modern imaging tools are closely linked to rapid development of minimally invasive surgery in patients with urinary incontinence and insights gained in continence mechanisms. METHODS: Whereas ultrasonography is a cost-efficient and readily available diagnostic tool for a routine use, the more expensive functional MRI, as a tool with more precise visualization of functional interactions and spatial representation of anatomical structures of the pelvic floor, is suitable for complex diagnostic purposes and scientific research. Both tools are already well established for evaluations of the female pelvic floor. For evaluation of the male pelvic floor, and in particular postprostatectomy incontinence, perineal ultrasonography and functional cine MRI are becoming increasingly evident. CONCLUSION: Further development of both imaging tools will contribute to new insights into the continence mechanism and improve the techniques of radical prostatectomy and minimally invasive surgery of male and female urinary incontinence in the future. PMID- 26162273 TI - [Cross-sectional imaging evaluation of renal masses]. AB - Cross-sectional imaging modalities including multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) are the diagnostic standard in detection, characterization, and staging of renal masses due to their high sensitivity and specificity. Currently, most renal masses are incidentally diagnosed by imaging for other medical reasons. Recent developments have improved image acquisition with high resolution, while simultaneously reducing radiation dose. CT imaging is the most accessible cross-sectional imaging method and is, therefore, the standard technique. MRI is indicated in patients who are allergic to intravenous CT contrast medium, in patients with renal insufficiency, or in younger patients. Further characterization of renal masses is possible with functional imaging including dual energy CT, perfusion CT, or diffusion-weighted MRI. Contrast-enhanced ultrasound allows detection of even subtle enhancement in hypovascular lesions with high sensitivity and can add valuable information to CT and MRI studies. PMID- 26162274 TI - [Ferdinand Eisenberger research stipendium 2015]. AB - The Ferdinand Eisenberger scholarship program provides interested young urologists with the chance to undertake intensive experimental investigations for a 1-year period outside the clinical routine. Within the framework of a scientific project scholarship holders acquire competence in research and establish important contacts for themselves as well as for their institutions to scientists and research laboratories excelling in basic research. In contrast to scholarships awarded by the large funding institutions, such as the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and German Cancer Aid (Deutsche Krebshilfe), the Eisenberger scholarships concentrate on host laboratories in Germany. In this way the German Society of Urology (DGU) hopes to strengthen the research infrastructure of urology in Germany with effective regional and national networks. PMID- 26162275 TI - [Adjuvant radiotherapy following radical prostatectomy for prostate cancer]. PMID- 26162276 TI - [Non-interventional study of metastatic castration-resistant prostate cancer. Prospective, non-interventional trial on the influence of adherence to abiraterone treatment in patients with metastatic, castrate-resistant prostate cancer (IMPACT) - trial AP 76/13 of the AUO]. PMID- 26162277 TI - [Radionuclide therapy and diagnostics in urology]. AB - In recent years there has been methodological improvement in established nuclear medicine procedures, such as renal and skeletal scintigraphy and new very specific probes for treatment and diagnosis of urological diseases have been introduced into the clinical routine. New diagnostic methods, such as positron emission tomography (PET) using prostate-specific membrane antigen (PSMA) ligands for highly accurate tumor localization in recurrent prostate cancer have become available in many centers. The very high and selective accumulation of these PSMA ligands in tumor tissue has shown promising therapeutic results. Moreover, since 2013 a new radiopharmaceutical agent, radium-223 dichloride, has been approved for treatment of symptomatic bone metastases of prostate cancer. Better knowledge of indications, benefits and limitations of these procedures will help clinicians to adequately introduce them into patient management. This article summarizes the state of the art in established nuclear medicine procedures for urological disorders and also reports on new diagnostic and therapeutic possibilities. PMID- 26162278 TI - A proteomic profiling of laser-microdissected lung adenocarcinoma cells of early lepidic-types. AB - BACKGROUND: In the new pathologic classification of lung adenocarcinoma proposed by IASLC/ATS/ERS in 2011, lepidic type adenocarcinomas are constituted by three subtypes; adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and lepidic predominant invasive adenocarcinoma (LPIA). Although these subtypes are speculated to show sequential progression from preinvasive lesion to invasive lung cancer, changes of protein expressions during these processes have not been fully studied yet. This study aims to glimpse a proteomic view of the early lepidic type lung adenocarcinomas. METHODS: A total of nine formalin-fixed and paraffin-embedded (FFPE) lepidic type lung adenocarcinoma tissues were selected from our archives, three tissues each in AIS, MIA and LPIA. The tumor and peripheral non-tumor cells in these FFPE tissues were collected with laser microdissection (LMD). Using liquid chromatography-tandem mass spectrometry (MS/MS), protein compositions were compared with respect to the peptide separation profiles among tumors collected from three types of tissues, AIS, MIA and LPIA. Proteins identified were semi-quantified by spectral counting-based or identification-based protein-based approach, and statistical evaluation was performed by pairwise G-tests. RESULTS: A total of 840 proteins were identified. Spectral counting-based semi-quantitative comparisons of all identified proteins through AIS to LPIA have revealed that the protein expression profile of LPIA was significantly differentiated from other subtypes. 70 proteins including HPX, CTTN, CDH1, EGFR, MUC1 were found as LPIA-type marker candidates, 15 protein candidates for MIA-type marker included CRABP2, LMO7, and NPEP, and 26 protein candidates for AIS-type marker included LTA4H and SOD2. The STRING gene set enrichment resulted from the protein-protein interaction (PPI) network analysis suggested that AIS was rather associated with pathways of focal adhesion, adherens junction, tight junction, that MIA had a strong association predominantly with pathways of proteoglycans in cancer and with PI3K-Akt. In contrast, LPIA was associated broadly with numerous tumor-progression pathways including ErbB, Ras, Rap1 and HIF-1 signalings. CONCLUSIONS: The proteomic profiles obtained in this study demonstrated the technical feasibility to elucidate protein candidates differentially expressed in FFPE tissues of LPIA. Our results may provide candidates of disease-oriented proteins which may be related to mechanisms of the early-stage progression of lung adenocarcinoma. PMID- 26162280 TI - Deciphering the Cellular Targets of Bioactive Compounds Using a Chloroalkane Capture Tag. AB - Phenotypic screening of compound libraries is a significant trend in drug discovery, yet success can be hindered by difficulties in identifying the underlying cellular targets. Current approaches rely on tethering bioactive compounds to a capture tag or surface to allow selective enrichment of interacting proteins for subsequent identification by mass spectrometry. Such methods are often constrained by ineffective capture of low affinity and low abundance targets. In addition, these methods are often not compatible with living cells and therefore cannot be used to verify the pharmacological activity of the tethered compounds. We have developed a novel chloroalkane capture tag that minimally affects compound potency in cultured cells, allowing binding interactions with the targets to occur under conditions relevant to the desired cellular phenotype. Subsequent isolation of the interacting targets is achieved through rapid lysis and capture onto immobilized HaloTag protein. Exchanging the chloroalkane tag for a fluorophore, the putative targets identified by mass spectrometry can be verified for direct binding to the compound through resonance energy transfer. Using the interaction between histone deacetylases (HDACs) and the inhibitor, Vorinostat (SAHA), as a model system, we were able to identify and verify all the known HDAC targets of SAHA as well as two previously undescribed targets, ADO and CPPED1. The discovery of ADO as a target may provide mechanistic insight into a reported connection between SAHA and Huntington's disease. PMID- 26162279 TI - Prognostic factors in the acute respiratory distress syndrome. AB - Despite improvements in critical care, acute respiratory distress syndrome (ARDS) remains a devastating clinical problem with high rates of morbidity and mortality. A better understanding of the prognostic factors associated with ARDS is crucial for facilitating risk stratification and developing new therapeutic interventions that aim to improve clinical outcomes. In this article, we present an up-to-date summary of factors that predict mortality in ARDS in four categories: (1) clinical characteristics; (2) physiological parameters and oxygenation; (3) genetic polymorphisms and biomarkers; and (4) scoring systems. In addition, we discuss how a better understanding of clinical and basic pathogenic mechanisms can help to inform prognostication, decision-making, risk stratification, treatment selection, and improve study design for clinical trials. PMID- 26162281 TI - Life Adaptation Skills Training (LAST) for persons with depression: A randomized controlled study. AB - BAKGROUND: To investigate the efficacy of the "Life Adaptation Skills Training (LAST)" program for persons with depression. METHODS: Sixty-eight subjects with depressive disorder were recruited from psychiatric outpatient clinics in Taipei city and were randomly assigned to either an intervention group (N=33), or a control group (N=35). The intervention group received 24-sessions of the LAST program, as well as phone contact mainly related to support for a total of 24 times. The control group only received phone contact 24 times. The primary outcome measure utilized was the World Health Organization Quality of Life-BREF Taiwan version. Secondary outcome measures included the Occupational self assessment, the Mastery scale, the Social support questionnaire, the Beck anxiety inventory, the Beck depression inventory-II, and the Beck scale for suicide ideation. The mixed-effects linear model was applied to analyze the incremental efficacy of the LAST program, and the partial eta squared (etap(2)) was used to examine the within- and between- group effect size. RESULTS: The subjects who participated in the LAST program showed significant incremental improvements with moderate to large between-group effect sizes on their level of anxiety (-5.45+/ 2.34, p<0.05; etap(2)=0.083) and level of suicidal ideation (-3.09+/-1.11, p<0.01; etap(2)=0.157) when compared to the control group. The reduction of suicidal ideations had a maintenance effect for three months after the end of intervention (-3.44+/-1.09, p<0.01), with moderate between-group effect sizes (etap(2)=0.101). Both groups showed significant improvement on overall QOL, overall health, physical QOL, psychological QOL, level of anxiety, and level of depression. The within-group effect sizes achieved large effects in the intervention group (etap(2)=0.328-0.544), and were larger than that of the control group. LIMITATIONS: A small sample size in the study, a high dropout rate, lower compliance rates for the intervention group, and lacking of true control group. CONCLUSIONS: The occupation-based LAST program, which focuses on lifestyle rearrangement and coping skills enhancement, could significantly improve the level of anxiety and suicidal ideations for persons with depression. PMID- 26162282 TI - Mood disorders in eating disorder patients: Prevalence and chronology of ONSET. AB - OBJECTIVES: In a clinical population, we estimated the frequency of mood disorders among 271 patients suffering from Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in comparison to a control group matched for age and gender. METHOD: The frequency of mood disorders was measured using the Mini International Neuropsychiatric Interview (MINI), DSM-IV version. RESULTS: Mood disorders were more frequent among eating disorder (ED) patients than among controls, with a global prevalence of the order of 80% for each ED group. The majority of the mood disorders comorbid with ED were depressive disorders (MDD and dysthymia). The relative chronology of onset of these disorders was equivocal, because mood disorders in some cases preceded and in others followed the onset of the eating disorders. LIMITATIONS: Our sample was characterized by patients with severe ED and high comorbidities, and thus do not represent the entire population of AN or BN. This also may have resulted in an overestimation of prevalence. CONCLUSION: Mood disorders appear significantly more frequently in patients seeking care for ED than in controls. These results have implications for the assessment and treatment of ED patients, and for the aetio-pathogenesis of these disorders. PMID- 26162283 TI - Effects of antiepileptic drugs on interictal epileptiform discharges in focal epilepsies: an update on current evidence. AB - Interictal epileptiform discharges (IEDs), occurring in the electroencephalograms (EEG) of patients with focal epilepsy, are crucial for diagnosis, while their relationship with seizure severity and recurrence is controversial. The effects of antiepileptic drugs (AEDs) on IEDs are even more debated. In general, it is currently believed by experts in the field that most of the classical AEDs do not significantly affect IEDs occurrence in these patients, and that monitoring their EEG effects during treatment is useless. In this review, we update the existing literature on the effects of classical and newer AEDs on focal IEDs, emphasizing the scarcity of data concerning the latter. We also discuss potential limits of available clinical and experimental data and future perspectives. PMID- 26162285 TI - Clinical characteristics and prognosis of heart failure in elderly patients. AB - OBJECTIVES: The aim of this study was to assess prevalence, clinical characteristics, and prognosis in elderly patients with heart failure with preserved ejection fraction (HFPEF) compared to patients with heart failure with reduced ejection fraction (HFREF) who were followed in an internal medicine unit. METHODS: In this retrospective observational study, the sample consisted of 301 patients followed in an internal medicine referral unit between January 2007 and December 2010. All patients were checked to determine their vital status on 31 December 2012. Survival was analyzed using Kaplan-Meier curves, and compared using the log-rank test. RESULTS: Of the 301 patients, 165 (54.8%) were women. In the 263 cases (87.4%) who underwent echocardiographic assessment, 190 (72.2%) had HFPEF and 73 (27.8%) had HFREF. Mean age was similar in the two groups (80.1 and 79.9 years; p=0.905), with a predominance of women in the HFPEF group (60.5% women, 42.5% men; p=0.025). The main etiology was hypertensive heart disease in the HFPEF group. Regarding treatment, more beta-blockers were administered in the HFREF group. No statistically significant differences were observed between the groups in terms of cardiovascular risk factors, comorbidities, NYHA functional class, or mortality. CONCLUSION: Clinical characteristics were similar for both HFPEF and HFREF patients. Women were predominant in the HFPEF group, as was hypertensive etiology. No significant differences in mortality were observed between the groups. PMID- 26162284 TI - Complications during colonoscopy: prevention, diagnosis, and management. AB - Colonoscopy is largely performed in daily clinical practice for both diagnostic and therapeutic purposes. Although infrequent, different complications may occur during the examination, mostly related to the operative procedures. These complications range from asymptomatic and self-limiting to serious, requiring a prompt medical, endoscopic or surgical intervention. In this review, the complications that may occur during colonoscopy are discussed, with a particular focus on prevention, diagnosis, and therapeutic approaches. PMID- 26162286 TI - Cardiovascular disease associated with human immunodeficiency virus: a review. AB - The cardiovascular manifestations of human immunodeficiency virus (HIV) infection have changed significantly following the introduction of highly active antiretroviral therapy (HAART) regimens. On one hand, HAART has altered the course of HIV disease, with longer survival of HIV-infected patients, and cardiovascular complications of HIV infection such as myocarditis have been reduced. On the other hand, HAART is associated with an increase in the prevalence of both peripheral and coronary arterial disease. As longevity increases in HIV-infected individuals, long-term effects, such as cardiovascular disease, are emerging as leading health issues in this population. In the present review article, we discuss HIV-associated cardiovascular disease, focusing on epidemiology, etiopathogenesis, diagnosis, prognosis, management and therapy. Cardiovascular involvement in treatment-naive patients is still important in situations such as non-adherence to treatment, late initiation of treatment, and/or limited access to HAART in developing countries. We therefore describe the cardiovascular consequences in treatment-naive patients and the potential effect of antiretroviral treatment on their regression, as well as the metabolic and cardiovascular implications of HAART regimens in HIV-infected individuals. PMID- 26162287 TI - Use of drug-eluting versus bare-metal stents after an acute coronary syndrome in Portugal: the EURHOBOP study. AB - INTRODUCTION AND OBJECTIVES: The interventional cardiologist chooses a specific stent type based on the risk-benefit profile for each case. In general, drug eluting stents should be considered in all clinical conditions, except if there are concerns or contraindications for prolonged dual antiplatelet therapy. The aim of this work was to describe the use of bare-metal vs. drug-eluting stents in patients undergoing percutaneous coronary intervention (PCI) after an acute coronary syndrome in Portuguese hospitals, according to patients' demographic and clinical characteristics and institutional characteristics. METHODS: Within the EURopean Hospital Benchmarking Processes (EURHOBOP) study, we retrospectively assessed 3009 consecutive patients in 10 Portuguese hospitals in 2009. Only patients with stents implanted during PCI (n=1194) were analyzed. RESULTS: A total of 425 patients (36%) received a bare-metal stent and 769 patients (64%) received a drug-eluting stent. A history of previous PCI, current non-ST elevation myocardial infarction, anterior descending artery as the infarct related artery and being initially admitted to a hospital with a catheterization laboratory were associated with drug-eluting stent implantation. Age under 45 or over 80, anemia and previous anticoagulation and/or atrial fibrillation were associated with bare-metal stent use. CONCLUSIONS: Approximately two-thirds of patients received drug-eluting stents, which were less frequently implanted in patients with ST-elevation myocardial infarction, aged over 80 years, female, with a previous history of stroke, anticoagulation and/or atrial fibrillation and anemia. Patients who had previously undergone PCI and those with the anterior descending artery as the infarct-related artery were more likely to receive a drug-eluting stent. PMID- 26162288 TI - Prognostic value of plasma neutrophil gelatinase-associated lipocalin in patients with heart failure. AB - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We sought to assess the prognostic value of this biomarker in patients with stable chronic heart failure (HF). METHODS: We studied 61 patients with chronic systolic HF who had been receiving optimal medical treatment for at least six months. Biomarkers were measured at baseline and included plasma NGAL, microalbuminuria, serum creatinine, and B-type natriuretic peptide (BNP). Estimated glomerular filtration rate (eGFR) was also calculated. Mean follow-up was 10.6+/-6.6 months. The primary endpoint was time to first cardiovascular event, defined as a combination of cardiovascular death, HF hospitalization or emergency department visit due to HF. Variables independently related to events were determined using a Cox proportional hazards model. RESULTS: Fifteen (24.6%) patients reached the primary endpoint. Patients with events were more likely to have worse renal function at baseline and also higher NGAL levels (median 316 [interquartile range 122-705] vs. 107 [78-170]; p=0.006). NGAL correlated significantly with creatinine (r=0.50; p<0.0001), albuminuria (r=0.33; p=0.008), and eGFR (r=-0.47; p=0.0001) but not with BNP (r=0.003; p=0.97). The best NGAL cutoff as determined by ROC curve analysis was 179 ng/ml. Event-free survival was lower in patients with NGAL above this cutoff. Variables independently related to events were NGAL (HR 1.0035, 95% CI 1.0019-1.0052; p<0.0001) and male gender (HR 5.9, 95% CI 1.22-28.6; p=0.028). CONCLUSION: NGAL correlated with other biomarkers of renal function but not with BNP and was independently associated with outcomes. PMID- 26162289 TI - Aortic valve replacement for severe aortic stenosis in octogenarians: patient outcomes and comparison of operative risk scores. AB - INTRODUCTION AND AIM: Isolated aortic valve replacement (AVR) in octogenarians is associated with increased operative risk, due to higher prevalence of associated risk factors and other comorbidities, making outcome prediction essential. We sought to analyze operative mortality and morbidity and to compare the predictive accuracy of the logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE) I, EuroSCORE II and Society of Thoracic Surgeons (STS) score in this population. METHODS: We retrospectively enrolled 106 consecutive octogenarians with symptomatic severe aortic stenosis undergoing isolated AVR in a large-volume single center between January 2003 and December 2010 and calculated surgical risk scores. RESULTS: Mean logistic EuroSCORE I, EuroSCORE II and STS score were 14.6+/-11, 4.4+/-3.1 and 4.0+/-2.4%, respectively. Mean operative mortality was 5.7% (six patients). Two (1.9%) patients suffered an ischemic stroke, three (2.8%) required temporary hemodialysis and five (4.7%) had a permanent pacemaker implanted. Five (4.7%) required rethoracotomy. No myocardial infarction or sternal wound infection was observed. Calibration-in-the large showed overestimation of operative mortality with logistic EuroSCORE I (p=0.036), whereas EuroSCORE II (p=1.0) and STS (p=1.0) showed good calibration. C-statistic values were 0.877 (95% CI 0.800-0.933) for logistic EuroSCORE I, 0.792 (95% CI 0.702-0.864) for EuroSCORE II and 0.702 (95% CI 0.605-0.787) for STS, without statistically significant differences. CONCLUSIONS: These results suggest that AVR can be performed safely in selected octogenarians. EuroSCORE II and STS demonstrated superior calibration and should be the preferred tools for risk assessment, at least for this population. PMID- 26162290 TI - Noncompaction and embolic myocardial infarction: the importance of oral anticoagulation. AB - Left ventricular noncompaction (LVNC) is characterized by left ventricular (LV) hypertrabeculations and is associated with heart failure, arrhythmias and embolism. We report the case of a 67-year-old LVNC patient, under oral anticoagulation (OAC) therapy for apical thrombosis. After she discontinued OAC, the thrombus involved almost the whole of the left ventricle; in a few months her condition worsened, requiring hospitalization, and despite heparin infusion she experienced myocardial infarction (MI), caused by embolic occlusion of the left anterior descending artery. Although infrequent as a complication of LVNC, and usually attributable to microvascular dysfunction, in this case MI seems due to coronary thromboembolism from dislodged thrombotic material in the left ventricle. PMID- 26162291 TI - Editorial comment on the article Aortic valve replacement for severe aortic stenosis in octogenarians: patient outcomes and comparison of operative risk scores. PMID- 26162292 TI - Frequency characteristics of neuromagnetic auditory steady-state responses to sinusoidally amplitude-modulated sweep tones. AB - OBJECTIVE: This study aimed to capture the neuronal frequency characteristics, as indexed by the auditory steady-state response (ASSR), relative to physical characteristics of constant sound pressure levels (SPLs). Relationship with perceptual characteristics (loudness model) was also examined. METHODS: Neuromagnetic 40-Hz ASSR was recorded in response to sinusoidally amplitude modulated sweep tones with carrier frequency covering the frequency range of 0.1 12.5kHz. Sound intensity was equalized at 50-, 60-, and 70-dB SPL with an accuracy of +/-0.5-dB SPL at the phasic peak of the modulation frequency. Corresponding loudness characteristics were modeled by substituting the detected individual hearing thresholds into a standard formula (ISO226:2003(E)). RESULTS: The strength of the ASSR component was maximum at 0.5kHz, and it decreased linearly on logarithmic scale toward lower and higher frequencies. Loudness model was plateaued between 0.5 and 4kHz. CONCLUSIONS: Frequency characteristics of the ASSR were not equivalent to those of SPL and loudness model. Factors other than physical and perceptual frequency characteristics may contribute to characterizing the ASSR. SIGNIFICANCE: The results contribute to the discussion of the most efficient signal summation for the generation of the ASSR at 0.5kHz and efficient neuronal processing at higher frequencies, which require less energy to retain equal perception. PMID- 26162293 TI - Distance to thrombus on MR angiography predicts outcome of middle cerebral artery occlusion treated with IV thrombolysis. AB - INTRODUCTION: The distance to thrombus (DT) on CT angiography was recently proposed as a predictor of outcome in patients treated by intravenous thrombolysis (IVT) for stroke due to occlusion of the middle cerebral artery (MCA). The purpose of the present study was to validate its inter-rater reliability and its prognostic value on contrast-enhanced magnetic resonance angiography (CE-MRA). Furthermore, we investigated the relation between DT and FLAIR-vascular hyperintensities (FVH) as a surrogate of collateral circulation and hypoperfusion. METHODS: Patients with acute MCA occlusions treated by IVT and diagnosed with magnetic resonance imaging (MRI) were included. Two readers measured DT. FVH and acute DWI lesion volumes were quantified. Clinical status was determined using the initial NIH stroke scale (NIHSS) and 90-day modified Rankin Scale (90d mRS). RESULTS: Sixty-one patients showed a lesion on diffusion weighted magnetic resonance images and an occlusion of the MCA on CE-MRA. We found significant inverse correlations between DT and NIHSS scores at admission (rho = -0.29; P = 0.02), DT and mRS at 90 days (rho = -0.29; P = 0.04), and between DT and FVH (rho = -0.32; P = 0.01). For a DT <22 mm, the likelihood of an unfavorable outcome (90d mRS 3-6 or NIHSS score improvement of <=10 points at discharge) was >50 %. Initial DWI lesion volumes showed no correlation with the outcome. Excellent inter-rater agreement for DT was observed (Cronbach's alpha = 0.98; P < 0.001). CONCLUSIONS: DT on CE-MRA is reliably measurable, correlates inversely with FLAIR-vascular hyperintensities, and predicts outcome in patients with acute MCA occlusion treated with IVT. PMID- 26162294 TI - Comparison of the early host immune response to two widely diverse virulent strains of Burkholderia pseudomallei that cause acute or chronic infections in BALB/c mice. AB - Burkholderia pseudomallei is the etiologic agent of melioidosis, which is endemic in Southeast Asia and Northern Australia. We previously found by the intraperitoneal (IP) route that we could discern differences in virulence in mice amongst different strains of B. pseudomallei. We report an early immune response study comparing two strains in our collection which represent the least, B. pseudomallei 1106a, and one of the most, HBPUB10134a, virulent strains in BALB/c mice. B. pseudomallei HBPUB10134a infected mouse spleens contained a 2-3 log higher bacterial burden than mice infected with B. pseudomallei 1106a 3 days post infection (PI). More and higher amounts of inflammatory cytokines/chemokines were detected in sera and spleen extracts from B. pseudomallei HBPUB10134a than B. pseudomallei 1106a infected mice. The most prominent were IFNgamma, IL-1alpha, IL 1beta, IL-6, IL-10, IP-10, and MIG. After 7 days PI, there was a decrease in bacterial burden in spleens from 1106a infected mice and a decrease in cytokines/chemokines in sera and spleen extracts from both sets of mice. By day 14 PI we saw an increase in monocytes/macrophages, NK cells, and granulocytes in spleens from both sets of mice. No B. pseudomallei HBPUB10134a infected mice survived after this time. In summary, B. pseudomallei HBPUB10134a was more virulent and induced host innate immune responses typical of a more acute-type infection than did B. pseudomallei 1106a which produced a more chronic infection in mice. PMID- 26162295 TI - Use of MALDI-TOF mass spectrometry to analyze the molecular profile of Pseudomonas aeruginosa biofilms grown on glass and plastic surfaces. AB - Biofilms are microbial sessile communities attached to surfaces that are known for causing many medical problems. A bacterial biofilm of clinical relevance is formed by the gram-negative bacteria Pseudomonas aeruginosa. During the formation of a biofilm, the initial adhesion of the cells is of crucial importance, and the characteristics of the contact surface have great influence on this step. In the present study, we aimed to use matrix-assisted laser desorption ionization time of-flight mass spectrometry (MALDI-TOF MS) profiling as a new methodology to monitor P. aeruginosa biofilm development. Biofilms were grown within polypropylene tubes containing a glass slide, and were harvested after 3, 5, 7, 9, or 12 days of inoculation. Planktonic cells were obtained separately by centrifugation as control. Two independent MALDI-TOF experiments were performed, one by collecting biofilms from both the glass slide and the polypropylene tube internal surface, and the other by acquiring biofilms from these surfaces separately. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to evaluate the morphological progression of the biofilm. The molecular results showed that MALDI profiling is able not only to distinguish between different biofilm stages, but it is also appropriate to indicate when the biofilm cells are released at the dispersion stage, which occurred first on polypropylene surface. Finally, the present study pointed out that MALDI profiling may emerge as a promising tool for the clinical diagnostic and prognostic workup of biofilms formation and control. PMID- 26162296 TI - ERCC1 as a Prognostic and Predictive Biomarker for Urothelial Carcinoma of the Bladder following Radical Cystectomy. AB - PURPOSE: ERCC1 is the key enzyme of the nucleotide excision repair pathway, which maintains genomic stability. ERCC1 has been proposed as a prognostic and predictive biomarker for patients with urothelial carcinoma of the bladder but there are limited data on patients after radical cystectomy. MATERIALS AND METHODS: ERCC1 was evaluated by immunohistochemistry in radical cystectomy specimens of 432 patients. Associations with disease-free and cancer specific survival, and the effect of adjuvant cisplatin based chemotherapy were assessed. Further, ERCC1 mRNA expression and in vitro sensitivity to cisplatin were correlated in 25 bladder urothelial carcinoma cell lines. RESULTS: ERCC1 was expressed in 308 tumors (71.3%). There was no association with clinicopathological variables (each p >0.3). Median postoperative followup was 128 months. On multivariable analyses patients with ERCC1 positive tumors had significantly better disease-free survival (HR 0.70, p = 0.028) and cancer specific survival (HR 0.70, p = 0.032) than those with ERCC1 negative tumors. Discrimination of the multivariable models increased by 0.7% to 0.9% following the inclusion of ERCC1. There was no modification of the effect of adjuvant cisplatin based combination chemotherapy by ERCC1 status (p = 0.38 and 0.88, respectively). There was also no correlation between ERCC1 and sensitivity to cisplatin in vitro (R(2) = 0.02, p = 0.46). CONCLUSIONS: ERCC1 may be a prognostic biomarker for urothelial carcinoma of the bladder. Patients with ERCC1 positive tumors may have better survival than those with ERCC1 negative tumors. However, the efficacy of adjuvant cisplatin based chemotherapy appears to be unrelated to ERCC1 status. PMID- 26162297 TI - Expression Analysis of DGKK during External Genitalia Formation. AB - PURPOSE: Genetic variants in diacylglycerol kinase kappa (DGKK) have been strongly associated with risk of hypospadias. We investigated the expression pattern of Dgkk during development of mouse external genitalia to better understand its function and mechanism in the etiology of hypospadias. MATERIALS AND METHODS: We performed Dgkk expression analysis via indirect immunofluorescence in histological sections of CD-1 mouse embryonic and postnatal male, female and diethylsilbestrol treated external genitalia. Histological findings were supplemented with DGKK expression analysis using quantitative real time polymerase chain reaction assays. RESULTS: In mouse external genitalia Dgkk was expressed in the membrane and cytoplasm of differentiating squamous epithelial cells of urethral plate/groove and epidermis but not in the undifferentiated epithelial cells of preputial lamina or basal layer of urethral groove epithelium. CD-1 gestation day 18 male mouse genital tubercle treated with oil or diethylstilbestrol showed similar patterns of Dgkk expression despite many morphological differences, including formation of preputial cleft observed in diethylsilbestrol treated mice. CONCLUSIONS: Dgkk appears to be a marker or mediator of squamous cell differentiation during development of mouse external genitalia. However, no association exists between Dgkk expression and formation of preputial cleft in the genital tubercle of diethylsilbestrol treated mice, suggesting that these 2 events may follow independent pathways in mice. Further studies are needed to elucidate the role of DGKK in hypospadias. PMID- 26162298 TI - Effects of Age and Bolus Volume on Velocity of Hyolaryngeal Excursion in Healthy Adults. AB - Reduced movement velocity has been identified as a risk marker for movement impairment in older adults. Hyolaryngeal excursion is a key movement feature of normal swallowing function which is known to change with age and other extrinsic variables such as bolus volume. However, velocity of hyolaryngeal excursion has received limited attention in the literature on normal or abnormal swallowing. This study evaluated the effects of age and bolus volume on the velocity of hyoid and laryngeal excursion during swallowing in healthy adults. Forty-four healthy volunteers were grouped into three age bands (young: 20-35 years, middle age: 36 55 years, older: 56 >= years). All subjects swallowed 5 and 20 mL of thin liquid during fluoroscopic recording. Fluoroscopic images were extracted for each swallow representing the onset and maximum excursion positions of the hyoid and larynx. Superior and anterior excursion distance (excursion magnitude) and the time difference between rest and maximum excursion (excursion duration) were calculated. Velocity was calculated as a ratio of distance over time. Superior hyoid excursion magnitude was significantly increased for the 20 mL volume. Anterior laryngeal excursion magnitude was also significantly increased for the 20 mL volume. No kinematic duration measure demonstrated significant change across age or bolus conditions. Superior hyoid excursion velocity was significantly faster for the 20 mL volume. Superior and anterior laryngeal excursion velocity were significantly faster for the 20 mL volume only in the older group. Results of this study indicate that magnitude and velocity of hyoid and laryngeal excursion vary with age and volume. Comprising both excursion magnitude and duration, kinematic velocity may be a more complete metric to evaluate age-related swallowing performance. PMID- 26162299 TI - Exploring the characteristics of the attentional blink paradigm when used to discover concealed knowledge. AB - Ganis and Patnaik (Appl Psychophysiol Biofeedback 34:189-196, 2009) reported that the attentional blink paradigm using faces could be used to detect the presence of concealed knowledge. The attentional blink is defined as the inability to successfully detect the second of two target items presented within a short inter stimulus interval. The present study tested the use of the attentional blink paradigm in a concealed knowledge test by investigating the effect that familiar faces may have on the attentional blink. Participants completed 200 trials where they were told to look for the same familiar target (Target 2; actor Brad Pitt) that was intermixed with neutral face stimuli and one other familiar face (Target 1; actor George Clooney). Target 1 was to act as the concealed knowledge as participants familiar with Target 1 would be distracted by his unannounced presence and report not seeing Target 2 thereby showing an attentional blink. Despite all participants being familiar with Target 2, an attentional blink still occurred, but with higher than normal Target 2 accuracy rates. Overall, we found support for using the AB paradigm with the concealed knowledge test; however, a possible countermeasure to the attentional blink is familiarity with Target 2 as eight of 21 participants who recognized Target 1 (the concealed knowledge) were also able to detect Target 2 on 100 % of the trials where Target 1's presence should have created an attentional blink. PMID- 26162300 TI - Anisotropic protein-protein interactions due to ion binding. AB - Self-association of proteins is strongly affected by long-range electrostatic interactions caused by equilibrium adsorption of small ions such as protons and multivalent metals. By affecting the molecular net charge, solution pH is thus a widely used parameter to tune stability and phase behavior of proteins. We here review recent studies where the charge distribution is perturbed not only by protons, but also by other binding ions, leading to a rich and inherently anisotropic charge distribution. Focus is on coarse grained simulation techniques, coupled to experiments of protein-protein interaction at varying salt and pH conditions. Finally, and with future bio-colloidal models in mind, we discuss the validity of coarse graining charge anisotropy using electric multipoles. PMID- 26162301 TI - Venous thromboembolism related to warm autoimmune hemolytic anemia: a case control study. AB - BACKGROUND: The risk of venous thromboembolism (VTE) during warm autoimmune hemolytic anemia (wAIHA) is apparent in several published series. Unlike proximate disorders (autoimmune thrombocytopenia, non-immune hemolytic diseases) little is known about the presentation and risk factors for VTE in this setting. OBJECTIVE: To determine the frequency, presentation and risk factors for VTE associated with wAIHA. METHODS: We performed a single center retrospective study of adult patients (>18years) followed for wAIHA between 2009 and 2013. VTE risk factors were systematically assessed. The characteristics of patients with or without VTE were compared. VTE presentation and precipitating factors were analyzed. The Padua VTE risk score was calculated in each case. RESULTS: Forty patients were included. wAIHA was idiopathic in 24 patients (60%). Twelve patients (30%) had Evans syndrome. Mean lowest hemoglobin level was 6.6g/dl [3.7 11.5]. Eight patients (20%) presented VTE after the appearance of wAIHA, at a mean age of 52.5years. All patients had pulmonary embolus, associated with a deep venous thrombosis in 4 cases. At the time of VTE 7/8 patients had frank hemolysis (median hemoglobin level: 7g/dL) and 6/8 were outpatients with a low Padua VTE risk score. The frequency of usual VTE risk factor was similar in cases and controls. By contrast, lowest hemoglobin level was significantly lower in patients that experienced VTE (5.3 vs 7.2g/dL, p=0.016). During the first episode of wAIHA, patients with concurrent VTE had a more pronounced anemia (5.3 vs 7.4g/dL, p=0.026). At the time of VTE, anemia was more severe when no other precipitating factor was present (6 vs 8.9g.dL, p=0.04). CONCLUSION: In our cohort, 20% of patients with wAIHA presented VTE. The vast majority of VTE occurred during severe hemolytic flares and were not attributable to usual VTE risk factors. VTE prophylaxis is advisable in any patient admitted for wAIHA, irrespective of Padua VTE risk score. Prophylaxis also seems reasonable for outpatients with marked hemolysis. PMID- 26162302 TI - Anti-SSA/SSB-negative Sjogren's syndrome shows a lower prevalence of lymphoproliferative manifestations, and a lower risk of lymphoma evolution. AB - OBJECTIVE: This study aims to compare clinical and laboratory features of patients who, while satisfying the American European Consensus Group (AECG) criteria for primary Sjogren's syndrome (SS), do not present the positivity for anti-Ro/SSA and/or anti-La/SSB, with patients that meet the AECG criteria and are positive for anti-Ro/SSA and/or anti-La/SSB. METHODS: 548 patients were selected based on the following criteria, and exclusion of patients negative for histopathology but positive for anti-Ro/SSA and anti-La/SSB: 1. Fulfilment of the AECG criteria, 2. Performance of minor salivary gland biopsy, 3. Search for anti Ro/SSA and anti-La/SSB, 4. Absence of hepatitis C virus infection. Univariate and multivariate analyses were performed. RESULTS: Two groups were compared: 342 patients were positive for both the histopathology and for anti-Ro/SSA and/or anti-La/SSB (H-only) and 206 patients were positive for histopathology, but negative for autoantibodies (H+SSA/SSB). The following variables were statistically found to be associated with H+SSA/SSB: younger age at diagnosis (p<0.0001), glandular swelling (p=0.01), purpura (p=0.04), leucopoenia (p=0.0001), lymphoma (p=0.002), low C3 (p=0.04), low C4 (p=0.01), hypergammaglobulinemia (p<0.0001), ANA (p<0.0001), rheumatoid factor (p<0.0001), and serum cryoglobulins (p=0.039). ANA positivity (OR 6.9), hypergammaglobulinemia (OR 5.1), positive rheumatoid factor (OR 2.3), and age at diagnosis (OR 0.97) were also selected by multivariate analyses as associated with H+SSA/SSB. CONCLUSION: Primary SS negative for anti-Ro/SSA and anti-La/SSB antibodies appears to be characterized by a lower risk of lymphoma and by a lower level of B-cell expansion. PMID- 26162303 TI - Pregnancy outcome and clinical status of gilts following experimental infection by H1N2, H3N2 and H1N1pdm09 influenza A viruses during the last month of gestation. AB - The present study was planned to study the effect of various subtypes of swine influenza virus (SIV) circulating among pigs (H1N2, H3N2 and emerging pandemic strain of H1N1 influenza A virus (H1N1pdm09) on the course of pregnancy in naive gilts experimentally infected during the last month of pregnancy. In addition, the clinical course of infection, distribution of viruses in various tissues (blood, placenta, fetal lung), and selected immunological, reproductive and productive parameters were also investigated. All SIV-inoculated gilts became infected. No abortions, stillbirths, intrauterine deaths or mummified fetuses were observed. No clinical signs of influenza virus infection or other disorders were observed in piglets born from infected and control gilts. There was a significant decrease in the number and frequency of lymphocytes in gilts inoculated with all influenza viruses. In general, the concentrations of IL-6, IL 10 and TNF-alpha were significantly higher in SIV-inoculated gilts as than in control animals, while IL-4 and IFN-gamma were not detected in plasma at any time post-inoculation in SIV- or mock-inoculated gilts. No evidence for transplacental transmission of SIV was found. Viremia was also not observed in any of the infected females. On the basis of recent results, we hypothesize that pregnancy failure observed during SIV infection under field conditions is probably related to high fever and pro-inflammatory cytokines rather than a direct effect of the virus on the placenta, embryo or fetus. PMID- 26162304 TI - Dose response of red imported fire ant colonies to Solenopsis invicta virus 3. AB - Baiting tests were conducted to evaluate the effect of increasing Solenopsis invicta virus 3 (SINV-3) dose on fire ant colonies. Actively growing early-stage fire ant (Solenopsis invicta Buren) laboratory colonies were pulse-exposed for 24 hours to six concentrations of SINV-3 (10(1), 10(3), 10(5), 10(7), 10(9) genome equivalents/MUl) in 1 ml of a 10 % sucrose bait and monitored regularly for two months. SINV-3 concentration had a significant effect on colony health. Brood rating (proportion of brood to worker ants) began to depart from the control group at 19 days for the 10(9) concentration and 26 days for the 10(7) concentration. At 60 days, brood rating was significantly lower among colonies treated with 10(9), 10(7), and 10(5) SINV-3 concentrations. The intermediate concentration, 10(5), appeared to cause a chronic, low-level infection with one colony (n = 9) supporting virus replication. Newly synthesized virus was not detected in any fire ant colonies treated at the 10(1) concentration, indicating that active infections failed to be established at this level of exposure. The highest bait concentration chosen, 10(9), appeared most effective from a control aspect; mean colony brood rating at this concentration (1.1 +/- 0.9 at the 60 day time point) indicated poor colony health with minimal brood production. No clear relationship was observed between the quantity of plus genome strand detected and brood rating. Conversely, there was a strong relationship between the presence of the replicative genome strand and declining brood rating, which may serve as a predictor of disease severity. Recommendations for field treatment levels to control fire ants with SINV-3 are discussed. PMID- 26162305 TI - New porcine epidemic diarrhoea virus variant with a large deletion in the spike gene identified in domestic pigs. AB - From October 2013 to date, approximately 1,000 outbreaks of porcine epidemic diarrhoea virus (PEDV) have occurred in Japan. Porcine epidemic diarrhoea with non-lethal effects in piglets was identified in Tottori prefecture in October 2014. Complete genome analysis revealed that the causative pathogen, Tottori2, is a new PEDV variant with a large (582 nt) deletion in the spike gene. Phylogenetic analysis indicated that the Tottori2 PEDV strain might have been derived from the current PEDV strains circulating in domestic pigs. Moreover, the Tottori2 PEDV strain was successfully isolated in Vero cells by serial passage. PMID- 26162306 TI - Use of Advanced Practice Providers as Part of the Urologic Healthcare Team. AB - Advanced practice providers (APPs) are advanced practice nurses (APN)/nurse practitioners (NP) or physician assistants. Over half of urologists currently employ APPs to extend and enhance their practice. Because APPs can fulfill a variety of roles from surgical assisting to running their own subspecialty clinic, they have emerged as a vital solution to alleviating the looming workforce shortage in urology practice. About 40 % of practicing urologists have not yet incorporated APPs into their practices. Some may still be unfamiliar with the concept of utilizing advanced practice providers, some have concerns about liability or scope of practice, and some are just getting started. Recently, the American Urological Association (AUA) published a consensus statement on advanced practice providers that provides urologists a comprehensive review regarding the education, training, Medicare reimbursement policies, applicable state laws, liability concerns, and examples of utilization of advanced practice providers within a urology practice. The consensus statement represented one of the most comprehensive compendiums of information specific to advanced practice providers in a urologic practice. This review will touch on the AUA Consensus Statement on Advanced Practice Providers, background information that informed that statement, as well as recent responses to the publication. PMID- 26162307 TI - Metaphors as Second Labels: Difficult for Preschool Children? AB - This study investigates the development of two cognitive abilities that are involved in metaphor comprehension: implicit analogical reasoning and assigning an unconventional label to a familiar entity (as in Romeo's 'Juliet is the sun'). We presented 3- and 4-year-old children with literal object-requests in a pretense setting (e.g., 'Give me the train with the hat'). Both age-groups succeeded in a baseline condition that used building blocks as props (e.g., placed either on the front or the rear of a train engine) and only required spatial analogical reasoning to interpret the referential expression. Both age groups performed significantly worse in the critical condition, which used familiar objects as props (e.g., small dogs as pretend hats) and required both implicit analogical reasoning and assigning second labels. Only the 4-year olds succeeded in this condition. These results offer a new perspective on young children's difficulties with metaphor comprehension in the preschool years. PMID- 26162308 TI - Prognostic signature of early lung adenocarcinoma based on the expression of ribonucleic acid metabolism-related genes. AB - OBJECTIVE: The current staging system for lung cancer is not sufficient to accurately identify those patients with early-stage tumors who would benefit from postsurgery chemotherapy. The objective of this study was to validate a prognostic signature based on the expression of 5 RNA (ribonucleic acid) metabolism-related genes. METHODS: Five lung cancer microarray datasets, 3 from adenocarcinomas and 2 from squamous cell carcinomas, were analyzed. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate the relationship between the classifier and recurrence and survival. RESULTS: Statistically significant differences in relapse-free survival and overall survival were observed when lung adenocarcinoma patients were divided into 3 risk groups. The prognostic information provided by the signature was independent from other demographic and disease variables, including stage. Significant differences in survival were observed between low- and high-risk groups in stage-IB patients: 5-year survival rates ranged from 83% to 100% in the low-risk groups, and from 30% to 71% in the high-risk groups, depending on the dataset. The RNA metabolism score additionally displayed an association with the benefit of adjuvant chemotherapy (P < .001), suggesting that those patients in the low-risk group are not good candidates for this treatment. CONCLUSIONS: The RNA metabolism signature is a prognostic marker that may be useful for predicting survival and optimizing the benefit of adjuvant chemotherapy in patients with lung adenocarcinoma. PMID- 26162309 TI - Piggyback technique facilitates off-pump coronary artery bypass graft by using a proximal anastamostic device with arterial conduits. PMID- 26162310 TI - Microparticles and endothelial function--A tour de force. PMID- 26162311 TI - Conservative behavior of fluorescence EEM-PARAFAC components in resin fractionation processes and its applicability for characterizing dissolved organic matter. AB - In this study, the applicability of the fluorescence excitation-emission matrix combined with parallel factor analysis (EEM-PARAFAC) was verified for resin fractionation processes, in which bulk dissolved organic matter (DOM) is separated into several fractions presumably having similar chemical structures. Here, four PARAFAC components, including three humic-like and one protein-like components, were identified from the EEMs of all DOM samples through fractionation procedures and the subtracted EEMs between before and after resins for different DOM sources (effluent, limnic, and riverine). The PARAFAC components exhibited conservative behavior upon resin fractionation, as indicated by the minimal difference in the PARAFAC components retained on resins calculated based on the direct subtraction of the components and the subtracted EEMs. The conservative behavior of PARAFAC components was more obvious compared with other fluorescent DOM (FDOM) indicators derived from peak-picking and fluorescence regional integration (FRI) methods. Humic-like components were more insensitive to resin fractionation than protein-like component. No consistency was found in the relative abundances of the PARAFAC components for the same resin fractions with different DOM sources, suggesting that the FDOM composition is more affected by DOM sources rather than by the resin fractions. Our study demonstrated that EEM-PARAFAC coupled with resin fractionation could provide detailed information on DOM by quantitatively comparing the individual PARAFAC components within different resin fractions. PMID- 26162312 TI - A hydrodynamics-based approach to evaluating the risk of waterborne pathogens entering drinking water intakes in a large, stratified lake. AB - Pathogen contamination of drinking water lakes and reservoirs is a severe threat to human health worldwide. A major source of pathogens in surface sources of drinking waters is from body-contact recreation in the water body. However, dispersion pathways of human waterborne pathogens from recreational beaches, where body-contact recreation is known to occur to drinking water intakes, and the associated risk of pathogens entering the drinking water supply remain largely undocumented. A high spatial resolution, three-dimensional hydrodynamic and particle tracking modeling approach has been developed to analyze the risk and mechanisms presented by pathogen dispersion. The pathogen model represents the processes of particle release, transport and survival. Here survival is a function of both water temperature and cumulative exposure to ultraviolet (UV) radiation. Pathogen transport is simulated using a novel and computationally efficient technique of tracking particle trajectories backwards, from a drinking water intake toward their source areas. The model has been applied to a large, alpine lake - Lake Tahoe, CA-NV (USA). The dispersion model results reveal that for this particular lake (1) the risk of human waterborne pathogens to enter drinking water intakes is low, but significant; (2) this risk is strongly related to the depth of the thermocline in relation to the depth of the intake; (3) the risk increases with the seasonal deepening of the surface mixed layer; and (4) the risk increases at night when the surface mixed layer deepens through convective mixing and inactivation by UV radiation is eliminated. While these risk factors will quantitatively vary in different lakes, these same mechanisms will govern the process of transport of pathogens. PMID- 26162313 TI - Statistical failure models for water distribution pipes - A review from a unified perspective. AB - This review describes and compares statistical failure models for water distribution pipes in a systematic way and from a unified perspective. The way the comparison is structured provides the information needed by scientists and practitioners to choose a suitable failure model for their specific needs. The models are presented in a novel framework consisting of: 1) Clarification of model assumptions. The models originally formulated in different mathematical forms are all presented as failure rate. This enables to see differences and similarities across the models. Furthermore, we present a new conceptual failure rate that an optimal model would represent and to which the failure rate of each model can be compared. 2) Specification of the detailed data assumptions required for unbiased model calibration covering the structure and completeness of the data. 3) Presentation of the different types of probabilistic predictions available for each model. Nine different models and their variations or further developments are presented in this review. For every model an overview of its applications published in scientific journals and the available software implementations is provided. The unified view provides guidance to model selection. Furthermore, the model comparison presented herein enables to identify areas where further research is needed. PMID- 26162314 TI - Building Data-Driven Pathways From Routinely Collected Hospital Data: A Case Study on Prostate Cancer. AB - BACKGROUND: Routinely collected data in hospitals is complex, typically heterogeneous, and scattered across multiple Hospital Information Systems (HIS). This big data, created as a byproduct of health care activities, has the potential to provide a better understanding of diseases, unearth hidden patterns, and improve services and cost. The extent and uses of such data rely on its quality, which is not consistently checked, nor fully understood. Nevertheless, using routine data for the construction of data-driven clinical pathways, describing processes and trends, is a key topic receiving increasing attention in the literature. Traditional algorithms do not cope well with unstructured processes or data, and do not produce clinically meaningful visualizations. Supporting systems that provide additional information, context, and quality assurance inspection are needed. OBJECTIVE: The objective of the study is to explore how routine hospital data can be used to develop data-driven pathways that describe the journeys that patients take through care, and their potential uses in biomedical research; it proposes a framework for the construction, quality assessment, and visualization of patient pathways for clinical studies and decision support using a case study on prostate cancer. METHODS: Data pertaining to prostate cancer patients were extracted from a large UK hospital from eight different HIS, validated, and complemented with information from the local cancer registry. Data-driven pathways were built for each of the 1904 patients and an expert knowledge base, containing rules on the prostate cancer biomarker, was used to assess the completeness and utility of the pathways for a specific clinical study. Software components were built to provide meaningful visualizations for the constructed pathways. RESULTS: The proposed framework and pathway formalism enable the summarization, visualization, and querying of complex patient-centric clinical information, as well as the computation of quality indicators and dimensions. A novel graphical representation of the pathways allows the synthesis of such information. CONCLUSIONS: Clinical pathways built from routinely collected hospital data can unearth information about patients and diseases that may otherwise be unavailable or overlooked in hospitals. Data-driven clinical pathways allow for heterogeneous data (ie, semistructured and unstructured data) to be collated over a unified data model and for data quality dimensions to be assessed. This work has enabled further research on prostate cancer and its biomarkers, and on the development and application of methods to mine, compare, analyze, and visualize pathways constructed from routine data. This is an important development for the reuse of big data in hospitals. PMID- 26162315 TI - Decreased urine uric acid excretion is associated with diabetic retinopathy but not with lower limb atherosclerosis in hospitalized patients with type 2 diabetes. AB - OBJECTIVE: To explore the associations between urine uric acid excretion (UUAE) and diabetic retinopathy (DR)/lower limb atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. METHODS: This cross-sectional study was conducted in 2529 hospitalized Chinese patients with type 2 diabetes. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartile based on UUAE levels. DR was determined by digital fundus photography. Lower limb atherosclerotic lesions were assessed by Doppler ultrasound. Both DR and lower limb atherosclerosis were compared among the UUAE quartile groups, respectively. RESULTS: There was a significant decrease in the prevalence of DR in patients across the UUAE quartiles after adjustment for sex, age and diabetic duration (35.0%, 30.7%, 26.1%, and 21.5%, respectively, p = 0.000001 for trend). A fully adjusted multiple logistic regression analyses revealed that UUAE quartiles were markedly inversely associated with the presence of DR (p = 0.030). The prevalence of lower limb plaque (73.9% vs. 62.6%, p = 0.000044) and stenosis (16.3% vs. 9.7%, p = 0.000015) was markedly higher in the diabetics with DR than in those without DR. However, there was no statistical association between the UUAE and lower limb atherosclerotic lesions in type 2 diabetes. CONCLUSIONS: Decreased UUAE was an independent risk factor for DR but not for lower limb atherosclerosis in hospitalized Chinese patients with type 2 diabetes. In selected populations, such as those with type 2 diabetes, the role of uric acid in atherosclerosis may be result from other concomitantly atherosclerotic risk factors, such as DR. PMID- 26162316 TI - Evaluation of HbA1c as a prognostic biomarker of cardiovascular events and mortality in nondiabetic patients: Methodological considerations. PMID- 26162317 TI - Ethnic disparity in central arterial stiffness and its determinants among Asians with type 2 diabetes. AB - OBJECTIVE: We previously reported ethnic disparity in adverse outcomes among Asians with type 2 diabetes (T2DM) in Singapore. Central arterial stiffness can aggravate systemic vasculopathy by propagating elevated systolic and pulse pressures forward, thereby accentuating global vascular injury. We aim to study ethnic disparity in central arterial stiffness and its determinants in a multi ethnic T2DM Asian cohort. METHODS: Arterial stiffness was estimated by carotid femoral pulse wave velocity (PWV) and augmentation index (AI) using applanation tonometry method in Chinese (N = 1045), Malays (N = 458) and Indians (N = 468). Linear regression model was used to evaluate predictors of PWV and AI. RESULTS: PWV was higher in Malays (10.1 +/- 3.0 m/s) than Chinese (9.7 +/- 2.8 m/s) and Indians (9.6 +/- 3.1 m/s) (P = 0.018). AI was higher in Indians (28.1 +/- 10.8%) than Malays (25.9 +/- 10.1%) and Chinese (26.1 +/- 10.7%) (P < 0.001). Malays remain associated with higher PWV (beta = 0.299, P = 0.048) post-adjustment for age, gender, duration of diabetes, hemoglobin A1c, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), soluble receptor for advanced glycation end-products, urinary albumin-to-creatinine ratio, and insulin usage, which were all independent predictors of PWV. Indians remain associated with higher AI (beta = 2.776, P < 0.001) post-adjustment for age, gender, BMI, SBP, DBP, and height, which were independent predictors of AI. These variables explained 27.7% and 33.4% of the variance in PWV and AI respectively. CONCLUSIONS: Malays and Indians with T2DM have higher central arterial stiffness, which may explain their higher risk for adverse outcomes. Modifying traditional major vascular risk factors may partially alleviate their excess cardiovascular risk through modulating arterial stiffness. PMID- 26162318 TI - Epigenetic Regulation of Cytosolic Phospholipase A2 in SH-SY5Y Human Neuroblastoma Cells. AB - Group IVA cytosolic phospholipase A2 (cPLA2 or PLA2G4A) is a key enzyme that contributes to inflammation via the generation of arachidonic acid and eicosanoids. While much is known about regulation of cPLA2 by posttranslational modification such as phosphorylation, little is known about its epigenetic regulation. In this study, treatment with histone deacetylase (HDAC) inhibitors, trichostatin A (TSA), valproic acid, tubacin and the class I HDAC inhibitor, MS 275, were found to increase cPLA2alpha messenger RNA (mRNA) expression in SH-SY5Y human neuroblastoma cells. Co-treatment of the histone acetyltransferase (HAT) inhibitor, anacardic acid, modulated upregulation of cPLA2alpha induced by TSA. Specific involvement of class I HDACs and HAT in cPLA2alpha regulation was further shown, and a Tip60-specific HAT inhibitor, NU9056, modulated the upregulation of cPLA2alpha induced by MS-275. In addition, co-treatment of with histone methyltransferase (HMT) inhibitor, 5'-deoxy-5'-methylthioadenosine (MTA) suppressed TSA-induced cPLA2alpha upregulation. The above changes in cPLA2 mRNA expression were reflected at the protein level by Western blots and immunocytochemistry. Chromatin immunoprecipitation (ChIP) showed TSA increased binding of trimethylated H3K4 to the proximal promoter region of the cPLA2alpha gene. Cell injury after TSA treatment as indicated by lactate dehydrogenase (LDH) release was modulated by anacardic acid, and a role of cPLA2 in mediating TSA induced injury shown, after co-incubation with the cPLA2 selective inhibitor, arachidonoyl trifluoromethyl ketone (AACOCF3). Together, results indicate epigenetic regulation of cPLA2 and the potential of such regulation for treatment of chronic inflammation. PMID- 26162319 TI - Mitochondrial DNA Haplogroup A Decreases the Risk of Drug Addiction but Conversely Increases the Risk of HIV-1 Infection in Chinese Addicts. AB - Drug addiction is one of the most serious social problems in the world today and addicts are always at a high risk of acquiring HIV infection. Mitochondrial impairment has been reported in both drug addicts and in HIV patients undergoing treatment. In this study, we aimed to investigate whether mitochondrial DNA (mtDNA) haplogroup could affect the risk of drug addiction and HIV-1 infection in Chinese. We analyzed mtDNA sequence variations of 577 Chinese intravenous drug addicts (289 with HIV-1 infection and 288 without) and compared with 2 control populations (n = 362 and n = 850). We quantified the viral load in HIV-1-infected patients with and without haplogroup A status and investigated the potential effect of haplogroup A defining variants m.4824A > G and m.8794C > T on the cellular reactive oxygen species (ROS) levels by using an allotopic expression assay. mtDNA haplogroup A had a protective effect against drug addiction but appeared to confer an increased risk of HIV infection in addicts. HIV-1-infected addicts with haplogroup A had a trend for a higher viral load, although the mean viral load was similar between carriers of haplogroup A and those with other haplogroup. Hela cells overexpressing allele m.8794 T showed significantly decreased ROS levels as compared to cells with the allele m.8794C (P = 0.03). Our results suggested that mtDNA haplogroup A might protect against drug addiction but increase the risk of HIV-1 infection. The contradictory role of haplogroup A might be caused by an alteration in mitochondrial function due to a particular mtDNA ancestral variant. PMID- 26162320 TI - Chromosome 4q25 Variants rs2200733, rs10033464, and rs1906591 Contribute to Ischemic Stroke Risk. AB - Previous studies have shown an association between chromosome 4q25 variants (rs2200733, rs10033464, and rs1906591) and the risk of ischemic stroke. However, the results are inconsistent. Thus, we conducted this meta-analysis to evaluate risk effect of chromosome 4q25 variants on ischemic stroke. We performed the literature search in PubMed and Embase through October 2014 for all the potentially relevant studies. The odds ratios (ORs), together with the corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate the strength of association. The search yielded eight studies (13 reports for rs2200733, 13 reports for rs10033464, and 7 reports for rs1906591). The ORs for overall ischemic stroke risk were 1.17 (95 % CI 1.09-1.26) for rs2200733*T, 1.02 (95 % CI 0.96-1.08) for rs10033464*T and 1.21 (95 % CI 1.10-1.32) for rs1906591*A. Stratified analysis by ischemic stroke subtypes revealed a stronger association between all the variants and cardioembolic stroke (CES) (OR = 1.41, 95 % CI 1.31-1.53 for rs2200733*T, OR = 1.18, 95 % CI 1.07-1.31 for rs10033464*T and OR = 1.51, 95 % CI 1.29-1.77 for rs1906591*A). The results of our meta analysis indicated that chromosome 4q25 variants are associated with ischemic stroke risk, in particular cardioembolic stroke (CES). PMID- 26162322 TI - Sub-lethal effects of Vip3A toxin on survival, development and fecundity of Heliothis virescens and Plutella xylostella. AB - The assessment of sub-lethal effects is important to interpret the overall insecticide efficacy in controlling insect pest populations. In addition to the lethal effect, sub-lethal effects may also occur in exposed insects. Vegetative insecticidal proteins (Vips) have shown a broad spectrum of insecticidal activity against many insect pest species. In this study the sub-lethal effects of the Bacillus thuringiensis vegetative insecticidal toxin Vip3A on the development and reproduction of Heliothis virescens F. and Plutella xylostella L. were evaluated in the laboratory. The results indicated that the sub-lethal concentration of Vip3A increased the duration of the larval and pupal stages as compared with the control treatment for both species. The percent pupation and percent adult emergence were significantly lower for Vip3A-treated insects. The proportion of pairs that produced eggs and the longevity of adults were not significantly different between treatments. H. virescens and P. xylostella treated with Vip3A showed an 11 and 17 % decrease in their intrinsic rate of increase (rm) respectively compared with untreated insects. The results from this study will be helpful to develop the strategy to incorporate Vip 3A containing crops in an integrated pest management programme. PMID- 26162321 TI - Enhanced Neuroprotection of Acetyl-11-Keto-beta-Boswellic Acid (AKBA)-Loaded O Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways. AB - Acetyl-11-keto-beta-boswellic acid (AKBA), a main active constituent from Boswellia serrata resin, is a novel candidate for therapy of cerebral ischemia reperfusion (I/R) injury. Nevertheless, its poor solubility in aqueous solvent, bioavailability, and rapid clearance limit its curative efficacy. To enhance its potency, in our study, AKBA-loaded o-carboxymethyl chitosan nanoparticle (AKBA NP) delivery system was synthesized. The transmission electron microscopy and transmission electron microscope images of AKBA-NPs suggested that particle size was 132 +/- 18 nm, and particles were spherical in shape with smooth morphology. In pharmacokinetics study, AKBA-NPs apparently increases the area under the curve of plasma concentration-time and prolonged half-life compared with AKBA. The tissue distribution study confirmed that AKBA-NPs had a better brain delivery efficacy in comparison with AKBA. The results from our pharmacodynamic studies showed that AKBA-NPs possess better neuroprotection compared with AKBA in primary neurons with oxygen-glucose deprivation (OGD) model and in animals with middle cerebral artery occlusion (MCAO) model. Additionally, AKBA-NPs modulate antioxidant and anti-inflammatory pathways more effectively than AKBA by increasing nuclear erythroid 2-related factor 2 and heme oxygenase-1 expression, and by decreasing nuclear factor-kappa B and 5-lipoxygenase expression. Collectively, our results suggest that AKBA-NPs serve as a potent delivery vehicle for AKBA in cerebral ischemic therapy. PMID- 26162323 TI - [Management of postpartum anal incontinence: A systematic review]. AB - AIM: To analyse the prevalence of postpartum anal incontinence, its risk factors, and its management. MATERIALS AND METHODS: A comprehensive systematic review of the literature on PubMed, Medline, Embase and Cochrane using: postpartum anal incontinence, postpartum fecal incontinence, perineal rehabilitation, anal surgery. RESULTS: The prevalence of postpartum anal incontinence varied from 4% (primipare) to 39% (multipare) at 6 weeks postpartum, whereas fecal incontinence can reach respectively 8 to 12% 6 years after delivery. Identified risk factors were: vaginal delivery (OR: 1.32 [95%CI: 1.04-1.68]) compared to cesarean section, instrumental extractions (OR: 1.47 [95%CI: 1.22-1.78]) compared to spontaneous vaginal delivery but it was only with forceps (OR: 1.50 [95%CI: 1.19 1.89]) and not with vaccum (OR: 1.31 [95%CI: 0.97-1.77]). Maternal age over 35 years (OR: 6 [95%CI: 1.85-19.45]), number of births (3 births: OR: 2.91 [95%CI: 1.32-6.41]) and the occurrence of anal-sphincter injury (OR: 2.3 [95%CI: 1.1-5]) were associated with an increased risk of anal incontinence regardless of the type of delivery compared to a group of women without anal incontinence. Perineal rehabilitation should be interpreted with caution because of the lack of randomized controlled trials. A reassessment at 6 months postpartum in order to propose a surgical treatment by sphincteroplasty could be considered if symptoms persist. The results of the sphincteroplasty were satisfactory but with a success rate fading in time (60 to 90% at 6 months against 50 to 40% at 5 and 10 years). CONCLUSION: Postpartum anal incontinence requires special care. Recommendations for the management of postpartum anal incontinence would be useful. PMID- 26162325 TI - Sulfur dioxide and benzo(a)pyrene trigger apoptotic and anti-apoptotic signals at different post-exposure times in mouse liver. AB - There is considerable concern that exposure to PAHs in combination with other air pollutants may lead to cancer or apoptosis in different cells. This study investigated the interaction effects between SO2 and BaP in mouse liver after long-term exposure. Mice were exposed to BaP for 5days or SO2 inhalation for 4weeks alone or together. The mitochondrial membrane potential (MMP) was assessed using the lipophilic cationic probe JC-1. The mRNA and protein level of several mitochondrial respiratory complex subunits and apoptosis-related genes were analyzed by real-time RT-PCR and/or western blot, respectively. We observed the pathology change of the mouse liver after 4-week treatments. It was revealed that MMP was reduced after co-exposure of SO2 and BaP after a 4-week treatment (1day post-exposure, p.e. 1d), with the suppression of the mRNA expression of complexes IV and V subunits, CO1, CO4, and ATP6. Co-exposure of SO2 and BaP appeared to be able to cause apoptotic signals, as judged by the suppression of bcl-2 and the bcl-2/bax ratio and the elevation of bax, caspase 3 activation, p53 accumulation and phosphorylation 1d post-exposure to SO2 and BaP, while the anti-apoptotic signal was detected by the elevation of bcl-2 and the bcl-2/bax ratio as well as the suppression of bax and p53 expression after a 13-week post-exposure (p.e. 13w) of SO2 and BaP. These results indicate that co-exposure to SO2 and BaP appears to lead to apoptotic as well as anti-apoptotic signals at different post exposure times. PMID- 26162324 TI - Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation. AB - Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson's trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility. PMID- 26162326 TI - Tentative reference values for environmental pollutants in blood or urine from the children of Kinshasa. AB - The DRC, as most of African nations, does not have a national biomonitoring programme and there is a lack of information on background levels of environmental pollutants in the general DRC population, particularly in children. The focus of the data presented in this report aims to establish the background levels of a range of environmental pollutants in urine or blood from the children population of Kinshasa. Based on the representative data collection of the Kinshasa population, the survey selected 125 children aged 1-14years and living in Kinshasa (6years on average, 56% of girls, 100% of non-smokers, without amalgam fillings and consumers of fish 3 times per week). Biomarkers of a range of metals (As, Cd, Hg and Pb), pyrene (PAH) and benzene were analyzed in the blood or urine samples. Globally, the results indicate that the exposure levels of children living in Kinshasa are 10 times higher than those published by the American, Canadian and German children surveys. This study provides the first Reference Values of environmental pollutants [As, Cd, Hg, Pb, pyrene (PAH) and benzene] in the Kinshasa children population and reveals elevated levels of all biomarkers studied. The data set of this study may allow environmental and health authorities of DRC to undertake a national biomonitoring programme, especially with four insights for the protection of human heath. PMID- 26162327 TI - Highly sensitive label free electrochemical detection of VGEF165 tumor marker based on "signal off" and "signal on" strategies using an anti-VEGF165 aptamer immobilized BSA-gold nanoclusters/ionic liquid/glassy carbon electrode. AB - In this work, a label free electrochemical aptasensor for the detection of ultra traces of vascular endothelial growth factor (VEGF165) based on "signal off" and "signal on" mechanisms of response was developed. The BSA-gold nanoclusters/ionic liquid (BSA-AuNCs/IL) was used as a suitable nanocomposite platform for immobilization of the aptamer on a glassy carbon electrode. In "signal off" mechanism, the interaction of VEGF165 with its anti-VEGF165 aptamers, resulted in desorption of methylene blue (MB) probe from aptamer and its release into solution. Consequently, the decrease in current intensity of the differential pulse voltammogram of adsorbed MB was monitored and found to be linearly proportional with increasing concentration of VEGF165 in sample solution in the range of 1-120 pM with a limit of detection of 0.32p M. While, in "signal on" mechanism, the interaction of immobilized anti-VEGF165 aptamers on the electrode surface with VEGF165, led to more mass-transfer limiting of the [Fe(CN)6](3-/4-) probe to the electrode surface. Therefore, the charge transfer resistance (Rct) of the probe was increased linearly with increasing concentration of VEGF165 in the range of 2.5-250 pM with a limit of detection of 0.48 pM. The experimental results demonstrated that both of these mechanisms are suitable for determination of low levels of the VEGF165 tumor marker in serum samples. PMID- 26162328 TI - A quantitative binding study of fibrinogen and human serum albumin to metal oxide nanoparticles by surface plasmon resonance. AB - The interaction of plasma proteins with metal oxide nanoparticles (NPs) is important due to the potential biomedical application of these NPs. In this study, new approaches were applied to measure quantitatively the kinetics and affinities of fibrinogen and human serum albumin (HSA) for TiO2, CeO2, Al2O3 and ZnO NPs immobilized on a sensor chip. Real-time surface plasmon resonance (SPR) measurements showed that fibrinogen interacted with TiO2 and CeO2 NPs with high affinity (135 and 40 pM, respectively) and to Al2O3 NPs with moderate affinity (15 nM). The data fitted well to the Langmuir model describing a 1:1 interaction. In contrast, HSA interacted with TiO2, CeO2 and Al2O3 NPs with lower affinity (80 nM, 37 nM and 2 uM, respectively) with the data fitting better to the conformational change model. TiO2 and CeO2 NPs had fast association rate constants with fibrinogen (1*10(6) M(-1) s(-1)) and Al2O3 NPs had a slower association rate constant (1*10(4) M(-1) s(-1)). By contrast, HSA had markedly slower association rate constants (1*10(3)-1*10(4) M(-1) s(-1)). The binding of the proteins was reversible, thus allowing the rapid capture of data for replicates. The occurrence of matrix effects was evaluated by using surfaces with different chemistries to capture the NPs, namely alginate, NeutrAvidin and bare gold. The affinity values determined for the NP-protein interactions were largely independent of the underlying surface used to capture the NPs. PMID- 26162329 TI - Targeted Next-Generation Sequencing for Hereditary Cancer Syndromes: A Focus on Lynch Syndrome and Associated Endometrial Cancer. AB - Lynch syndrome is a hereditary cancer syndrome that results from germline mutations in one of the DNA mismatch repair genes, leading to an increased lifetime risk of cancer. Colorectal cancer is most commonly identified with Lynch syndrome; however, women with Lynch syndrome have an increased risk of developing endometrial cancer (up to 60%), which is the sentinel diagnosis in approximately one-half of the cases. Current screening algorithms are developed on family history and laboratory-based tests, including immunohistochemistry for mismatch repair proteins and microsatellite instability testing. Next-generation sequencing assays are rapidly being incorporated into clinical laboratory practices and have diagnostic applications for hereditary cancer syndromes. Important challenges of next-generation sequencing include interpreting incidental and uncertain findings, counseling before and after testing, and informed consent of patients. Here, with the use of Lynch syndrome in endometrial cancer as a model, some of the applications and intricacies of next-generation sequencing testing for hereditary cancer syndromes are reviewed. PMID- 26162331 TI - A Novel Targeted Approach for Noninvasive Detection of Paternally Inherited Mutations in Maternal Plasma. AB - The challenge in noninvasive prenatal diagnosis for monogenic disorders lies in the detection of low levels of fetal variants in the excess of maternal cell-free plasma DNA. Next-generation sequencing, which is the main method used for noninvasive prenatal testing and diagnosis, can overcome this challenge. However, this method may not be accessible to all genetic laboratories. Moreover, shotgun next-generation sequencing as, for instance, currently applied for noninvasive fetal trisomy screening may not be suitable for the detection of inherited mutations. We have developed a sensitive, mutation-specific, and fast alternative for next-generation sequencing-mediated noninvasive prenatal diagnosis using a PCR-based method. For this proof-of-principle study, noninvasive fetal paternally inherited mutation detection was performed using cell-free DNA from maternal plasma. Preferential amplification of the paternally inherited allele was accomplished through a personalized approach using a blocking probe against maternal sequences in a high-resolution melting curve analysis-based assay. Enhanced detection of the fetal paternally inherited mutation was obtained for both an autosomal dominant and a recessive monogenic disorder by blocking the amplification of maternal sequences in maternal plasma. PMID- 26162330 TI - Fragile X Syndrome: Scientific Background and Screening Technologies. AB - Fragile X is the most common inherited cause of mental retardation with a prevalence of 1 in 4000 for males and 1 in 5000 to 8000 for females. The American College of Medical Genetics and Genomics has recommended diagnostic testing for fragile X in symptomatic persons, women with ovarian dysfunction, and persons with tremor/ataxia syndrome. Although medical and scientific professionals do not currently recommend screening nonsymptomatic populations, improvements in current treatment approaches and ongoing clinical trials have generated growing interest in screening for fragile X. Here, we briefly review the relevant molecular basis of fragile X and fragile X testing and compare three different molecular technologies available for fragile X screening in both males and females. These technologic approaches include destabilizing the CGG-repeat region with betaine and using chimeric CGG-targeted PCR primers, using heat pulses to destabilize C-G bonds in the PCR extension step, and using melting curve analysis to differentiate expanded CGG repeats from normals. The first two-step method performed with high sensitivity and specificity. The second method provided agarose gel images that allow identification of males with expanded CGG repeats and females with expanded CGG-repeat bands which are sometimes faint. The third melting curve analysis method would require controls in each run to correct for shifting optimal cutoff values. PMID- 26162332 TI - Growth overcompensation against O3 exposure in two Japanese oak species, Quercus mongolica var. crispula and Quercus serrata, grown under elevated CO2. AB - To assess the effects of elevated concentrations of carbon dioxide (CO2) and ozone (O3) on the growth of two mid-successional oak species native to East Asia, Quercus mongolica var. crispula and Quercus serrata, we measured gas exchange and biomass allocation in seedlings (initially 1-year-old) grown under combinations of elevated CO2 (550 MUmol mol(-1)) and O3 (twice-ambient) for two growing seasons in an open-field experiment in which root growth was not limited. Both the oak species showed a significant growth enhancement under the combination of elevated CO2 and O3 (indicated by total dry mass; over twice of ambient-grown plants, p < .05), which probably resulted from a preferable biomass partitioning into leaves induced by O3 and a predominant enhancement of photosynthesis under elevated CO2. Such an over-compensative response in the two Japanese oak species resulted in greater plant growth under the combination of elevated CO2 and O3 than elevated CO2 alone. PMID- 26162333 TI - Occurrence of organochlorine pesticides in the environmental matrices from King George Island, west Antarctica. AB - Antarctica is considered as a final sink of many persistent organic pollutants (POPs). This work aims to investigate the levels, distributions and potential sources of organochlorine pesticides (OCPs) with HRGC/HRMS technique. Twenty three OCPs were measured in various environmental matrices from King George Island, west Antarctica. The total concentrations (Sigma23OCPs) were at quite low levels, ranging 93.6-1260 pg g(-1) dry weight (dw) in soil and sediment, 223-1053 pg g(-1) dw in moss and 373-812 pg g(-1) dw in lichen. Hexachlorobenzene (HCB), dichloro-diphenyl-trichloroethane (DDT) and its metabolites (especially p,p'-DDE) and hexachlorocyclohexanes (HCHs) were the main contaminants in all samples. Lower alpha-HCH/gamma-HCH and higher p,p'-DDE/p,p'-DDT ratios compared with the technical products indicated long-range atmospheric transport (LRAT) of recent lindane and aged technical DDT. Significant dependence of many OCPs concentrations on total organic carbon (TOC) was observed. Apart from LRAT, local biotic activities could also contribute and influence the spatial distribution of the contaminants. PMID- 26162334 TI - Does ochre have the potential to be a remedial treatment for As-contaminated soils? AB - Ochre is an iron oxyhydroxide-rich waste that accumulates in water bodies associated with disused mines. Laboratory experiments were conducted to examine the potential of four different ochres to be used as remedial agents for As contaminated soils. The ochres removed As from solution (200 and 500 mg L(-1)) in adsorption experiments at pH 3 and 8 and, when added to As contaminated soil (5% w/w) significantly reduced As release to solution. In both these experiments the highest surface area ochres performed best. The impact of ochre amendments on uptake of As from soil by plants and humans and release of As to ground water was assessed in a year-long incubation study. Ochres increased soil pH and reduced CaCl2 extractable As but had no consistent effect on plant growth, plant As uptake or As extraction in physiologically-based extraction tests. Ochre may be better used for water treatment than soil remediation. PMID- 26162335 TI - Radioactive contamination of nest materials of the Eurasian Tree Sparrow Passer montanus due to the Fukushima nuclear accident: The significance in the first year. AB - The 2011 Fukushima nuclear accident contaminated large areas of eastern and northeastern Japan, releasing vast amounts of radiation. Here we investigated radioactive contamination of the nest materials of the Eurasian Tree Sparrow Passer montanus from the breeding season of 2011 directly after the accident to the next breeding season of 2012 at two sites. In Tokyo (222 km southwest of the plant), ambient dose rates in the nestboxes were lower than those in Ibaraki (175 km southwest of the plant), where the levels of 2011 were higher than those of 2012. Further, the amount of radioactive Cs in each nest increased with the increase in nest weight, with a higher increment at Ibaraki than at Tokyo. These data suggested higher nest contamination levels in the breeding season directly after a nuclear accident than in later seasons, and an increment of nest contamination levels via nest materials of birds. PMID- 26162336 TI - Binding characteristics of psoralen with trypsin: Insights from spectroscopic and molecular modeling studies. AB - Psoralen (PSO) is a naturally occurring furanocoumarin with a variety of pharmacological activities, however very limited information on the interaction of PSO with trypsin is available. In this study, the binding characteristics between PSO and trypsin at physiological pH were investigated using a combination of fluorescence, UV-vis absorption, circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopic, chemometric and molecular modeling approaches. It was found that the fluorescence quenching of trypsin by PSO was a static quenching procedure, ascribing the formation of a PSO-trypsin complex. The binding of PSO to trypsin was driven mainly by hydrophobic forces as the positive enthalpy change and entropy change values. The molecular docking showed that PSO inserted into the active site pocket of trypsin to interact with the catalytic residues His57, Asp102 and Ser195 and may cause a decrease in trypsin activity. The results of CD and FT-IR spectra along with the temperature-induced denaturation studies indicated that the addition of PSO to trypsin led to the changes in the secondary structure of the enzyme. The concentration profiles and spectra of the three components (PSO, trypsin, and PSO-trypsin complex) obtained by multivariate curve resolution-alternating least squares analysis exhibited the kinetic processes of PSO-trypsin interaction. This study will be helpful to understand the mechanism of PSO that affects the conformation and activity of trypsin in biological processes. PMID- 26162337 TI - The synthesis and modification of CdTe/CdS core shell quantum dots. AB - A simple and economical synthesis method of CdTe quantum dots (QDs) has been developed using glutathione as a modifier in an aqueous system. The fluorescent properties of as-prepared CdTe QDs at different reaction times were studied to optimize the synthesis conditions. CdTe/CdS QDs with core-shell structure was obtained by modifying as-synthesized CdTe QDs with refluxing and microwave method, respectively. The properties of the CdTe/CdS QDs were thoroughly investigated by photoluminescence (PL) and inverted fluorescence microscope, and exhibited high fluorescence intensity and good optical property. The study also shows that the microwave synthesis of CdTe/CdS QDs had more dispersed particle size and higher fluorescence intensity. PMID- 26162338 TI - Effect of curve crossing induced dissociation on absorption and resonance Raman spectra: An analytically solvable model. AB - An analytically solvable model for the crossing of a harmonic and a Morse potential coupled by Dirac Delta function has been proposed. Further we explore the electronic absorption spectra and resonance Raman excitation profile using this model and found that curve crossing had significant effect on the resonance Raman excitation profile. PMID- 26162339 TI - Evaluation of substituted methyl cyclohexanone hybrids for anti-tubercular, anti bacterial and anti-fungal activity: Facile syntheses under catalysis by ionic liquids. AB - An library of unresolved racemic Mannich bases incorporating two stereogenic carbon centers was evaluated for antibacterial activity against clinically isolated Gram-positive bacteria i.e. Staphylococcus aureus, Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and for antifungal activity against Candida albicans strains. Additionally, the susceptibility of microorganisms to Mannich bases prompted us to evaluate the potential for anti tubercular activity against clinically isolated Mycobacterium tuberculosis and virulent H37Rv strains. All compounds showed potent activity against M. tuberculosis strains at MIC ranging from 50 MUg/mL to 6.25 MUg/mL of concentration. Facile one pot Mannich type syntheses of rac-(2S)-2-[(R)-[(4 substituted phenyl){[4-(4-substituted phenyl)-1,3-thiazol-2 yl]amino}methyl]cyclohexanone derivatives were achieved by reactions of various 2 amino-4-aryl-thiazoles, appropriately substituted aromatic aldehydes and cyclohexanone in Bronsted acidic quaternary ammonium sulfated ionic liquids serving as dual solvents and catalysts. PMID- 26162340 TI - Preparation and photochromic properties of layer-by-layer self-assembly films and light-responsive micelles based on amphiphilic naphthopyran derivative. AB - An amphiphilic naphthopyran derivative (DSNP) with negative-charged di sulfatoethoxy was first designed and synthesized. DSNP was used to prepare the LBL self-assembly films with cationic quaternized poly(4-vinylpyridine) (P4VPQ). The multilayer assembly process was monitored via UV-Vis spectra and the DSNP displayed a significant slow fading rate in film. In addition, DSNP was also used as the light-responsive group to fabricate light-responsive micelles with polyethylene glycol-triethylamine bromide (PEG-NEt3). The photoisomerization of naphthopyran moieties can rapidly and reversibly tune the disassembly and re assembly of the micelles. The changes of fluorescent spectra of Nile Red (NR) in water solution of polymeric micelles demonstrated that the polymeric micelle can be used as nanocarriers to encapsulate, release and re-encapsulate guest solutes on demand controlling of light irradiation. The results indicate that the amphiphilic naphthopyran can be used in both optical-switches and biomedical area for drug delivery. PMID- 26162341 TI - Miniaturization of spectrophotometry based on micro flow analysis using norfloxacin as less-toxic reagent for iron determination. AB - A micro flow analysis (MUFA) system has been designed and fabricated for determination of total iron. The system consists of a microchannels fabricated by etching the polymethyl methacrylate (PMMA) by using laser ablation techniques and a sealed polydimethylsiloxane (PDMS) as top plate. The PMMA micro-flow was topped with a home-made polydimethylsiloxane (PDMS) micro-flow through cell, which was integrated with light emitting diode (LED) as light source and a USB 2000 spectrometer as detector. The proposed MUFA system was applied to determination of Fe(III) using norfloxacin as a less-toxic complexing agent in an acetate buffer solution pH 4.0, resulting in a yellow colored complex which gave the maximum absorption at 430nm. Under the optimum conditions, a linear calibration graph was obtained in the concentration range of 0.20-5.00mgL(-1). The limit of detection (LOD, defined as 3sigma) and limit of quantification (LOQ, defined as 10sigma) were 0.12 and 0.45mgL(-1), respectively. The relative standard deviation (R.S.D.) for repeatability and reproducibility were less than 1.50% and 1.24% (n=11) for 0.2mgL(-1) and 1.0mgL(-1) Fe(III), respectively. The proposed method was successfully applied to the determination of total iron in water samples, validated by the FAAS standard method after digestion by HNO3 and H2O2. PMID- 26162342 TI - A comparative study of the novel spectrophotometric methods versus conventional ones for the simultaneous determination of Esomeprazole magnesium trihydrate and Naproxen in their binary mixture. AB - Two novel simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra are developed and validated for simultaneous determination of Esomeprazole magnesium trihydrate (ESO) and Naproxen (NAP) namely; absorbance subtraction and ratio difference. The results were compared to that of the conventional spectrophotometric methods namely; dual wavelength and isoabsorptive point coupled with first derivative of ratio spectra and derivative ratio. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of ESO and NAP in their laboratory prepared mixtures and pharmaceutical preparation. No preliminary separation steps are required for the proposed spectrophotometeric procedures. The statistical comparison showed that there is no significant difference between the proposed methods and the reported method with respect to both accuracy and precision. PMID- 26162343 TI - Monitoring As and Hg variation in An-Gong-Niu-Huang Wan (AGNH) intermediates in a pilot scale blending process using laser-induced breakdown spectroscopy. AB - Laser-induced breakdown spectroscopy (LIBS) was used to assess the cinnabar and realgar blending of An-Gong-Niu-Huang Wan (AGNH) in a pilot-scale experiment, including the blending end-point. The blending variability of two mineral medicines, cinnabar and realgar, were measured by signal relative intensity changing rate (RICR) and moving window standard deviation (MWSD) based on LIBS. Meanwhile, relative concentration changing rate (RCCR) was obtained based on the reference method involving inductively coupled plasma optical emission spectrometry (ICP-OES). The LIBS result was consistent with ICP-OES at blending end-point determinations of both mineral medicines. Unlike the ICP-OES method, LIBS does not have an elaborate digestion procedure. LIBS is a promising and rapid technique to understand the blending process of Chinese Materia Medica (CMM) containing cinnabar and realgar. These results demonstrate the potential of LIBS in monitoring CMM pharmaceutical production. PMID- 26162344 TI - Factors affecting the relation between stretching frequencies and bond lengths. Diatomic and polyatomic species without adjustable fitting parameters. AB - In 76 sets of similar type bonds in species A2, AB, AB2, AB3, and AB4 the stretching frequency, nu, is related to the bond length, r, by nu=a/(rMU(1/2))-b, where MU is the reduced mass. The sets treated include all ground states for which spectroscopic date were found for stable molecules, free radicals, carbenes and other species with unsatisfied valences, both ionic and covalent. The linear correlation coefficients of each set are always greater than 0.998. The slopes a and intercepts b are defined by the data of each set and vary widely. They become congruent, but not exactly identical, when a is multiplied by the square root of the mean value of the number of electrons in the valence shell of the two bonded atoms, the electrons that become joined in the molecular orbitals formed upon bonding. No adjustable parameters are used. The number of bonds treated, over 300, is not as important as the fact that all species found were treated. The aim is not to add yet another parametric correlation to the many extant, but to better understand the relation between these two fundamental properties of chemical bonds. PMID- 26162345 TI - An SEM-EDX and Raman spectroscopic study of the fibrous arsenate mineral liskeardite and in comparison with other arsenates kankite, scorodite and yvonite. AB - The mineral liskeardite, an arsenate mineral with major cations of iron and aluminium, has been studied by a combination of scanning electron microscopy with energy dispersive spectroscopy and Raman spectroscopy. The mineral shows a fibrous nature. Semi-quantitative chemical analysis shows an Al and Fe arsenate phase with minor amounts of K, Cu, S and Si. Scanning electron microscopy shows a fibrous material. Intense Raman bands at 893, 867 and 843 cm(-1) are assigned to the nu1 and nu3 AsO4(3)(-) and HOAsO3(2)(-) symmetric and antisymmetric stretching vibrations. Raman bands are observed at 514, 499, 485 and 477 cm(-1) and are assigned to the nu4 out of plane bending modes of the AsO4(3)(-) and HOAsO3(2)(-) units. The series of bands at 373, 356 and 343 cm(-1) are assigned to the nu2 symmetric bending modes. Two groups of OH stretching bands are observed and assigned to OH unit and water stretching vibrations. A comparison of the Raman spectrum of liskeardite with scorodite, kankite and yvonite is made. PMID- 26162346 TI - Molecular interactions of flavonoids to pepsin: Insights from spectroscopic and molecular docking studies. AB - In the work described on this paper, the inhibitory effect of 10 flavonoids on pepsin and the interactions between them were investigated by a combination of spectroscopic and molecular docking methods. The results indicated that all flavonoids could bind with pepsin to form flavonoid-pepsin complexes. The binding parameters obtained from the data at different temperatures revealed that flavonoids could spontaneously interact with pepsin mainly through electrostatic forces and hydrophobic interactions with one binding site. According to synchronous and three-dimensional fluorescence spectra and molecular docking results, all flavonoids bound directly into the enzyme cavity site and the binding influenced the microenvironment and conformation of the pepsin activity site which resulted in the reduced enzyme activity. The present study provides direct evidence at a molecular level to understand the mechanism of digestion caused by flavonoids. PMID- 26162347 TI - A Multi-Analytical Approach for the Evaluation of the Efficiency of the Conservation-Restoration Treatment of Moroccan Historical Manuscripts Dating to the 16th, 17th, and 18th Centuries. AB - The most critical steps during the conservation-restoration treatment applied in Moroccan libraries are the deacidification using immersion in a saturated aqueous calcium hydroxide (Ca(OH)2) solution and the consolidation of degraded manuscripts using Japanese paper. The present study aims to assess the efficiency of this restoration method using a multi-analytical approach. For this purpose, three ancient Arabic Moroccan manuscript papers dating back to the 16th, 17th, and 18th centuries were investigated to characterize the paper support and make a comparative study between pre-restoration and post-restoration states. Three structural and molecular characterization techniques including solid-state nuclear magnetic resonance spectroscopy on (13)C with cross-polarization and magic-angle spinning nuclear magnetic resonance ((13)C CP-MAS NMR), attenuated total reflectance Fourier transform infrared spectroscopy (ATR FT-IR), and X-ray diffraction (XRD) were used to elucidate the cellulose main features, to identify the inorganic composition of the papers, and to study the crystallinity of the samples. Inductively coupled plasma atomic emission spectrometry (ICP-AES) allowed us to obtain a qualitative and quantitative characterization of the mineral fillers used in the manufacturing of the papers. Scanning electron microscopy coupled to energy dispersive spectrometry (SEM-EDS) ascertained the state of conservation of the different papers and helped us to study the elemental composition of the samples. After restoration, it was shown that the deacidification improved the stability of papers by providing an important alkaline buffer, as demonstrated using FT-IR and energy dispersive spectrometry (EDS) results. However, XRD and ICP-AES did not confirm the pertinence of the treatment for all samples because of the unequal distribution of Ca on the paper surface during the restoration. The consolidation process was studied using SEM analysis; its effectiveness in restoring torn areas was found to be significant. PMID- 26162348 TI - Towards the elimination of tuberculosis and a reduction in chest diseases. PMID- 26162349 TI - Vitamin D and tuberculosis: more effective in prevention than treatment? PMID- 26162350 TI - A killer combination that must be stopped. PMID- 26162351 TI - Costs of diagnostic algorithms: whose perspective counts? PMID- 26162352 TI - Diabetes mellitus and tuberculosis: programmatic management issues. AB - In August 2011, the World Health Organization and the International Union Against Tuberculosis and Lung Disease launched the Collaborative Framework for Care and Control of Tuberculosis (TB) and diabetes mellitus (DM) to guide policy makers and implementers in combatting the epidemics of both diseases. Progress has been made, and includes identifying how best to undertake bidirectional screening for both diseases, how to provide optimal treatment and care for patients with dual disease and the most suitable framework for monitoring and evaluation. Key programmatic challenges include the following: whether screening should be directed at all patients or targeted at those with high-risk characteristics; the most suitable technologies for diagnosing TB and diabetes in routine settings; the best time to screen TB patients for DM; how to provide an integrated, coordinated approach to case management; and finally, how to persuade non communicable disease programmes to adopt a cohort analysis approach, preferably using electronic medical records, for monitoring and evaluation. The link between DM and TB and the implementation of the collaborative framework for care and control have the potential to stimulate and strengthen the scale-up of non communicable disease care and prevention programmes, which may help in reducing not only the global burden of DM but also the global burden of TB. PMID- 26162353 TI - Fighting ambient air pollution and its impact on health: from human rights to the right to a clean environment. AB - Clean air is one of the basic requirements of human health and well-being. However, almost nine out of 10 individuals living in urban areas are affected by air pollution. Populations living in Africa, South-East Asia, and in low- and middle-income countries across all regions are the most exposed. Exposure to outdoor air pollution ranks as the ninth leading risk factor for mortality, killing 3.2 million people each year, especially young children, the elderly, persons with lung or cardiovascular disease, those who work or exercise outdoors and low-income populations. In October 2013, the International Agency for Research on Cancer (IARC) classified outdoor air pollution as carcinogenic to humans, calling air pollution 'a major environmental health problem'. Human rights and environmental norms are powerful tools to combat air pollution and its impact on health. The dependence of human rights on environmental quality has been recognised in international texts and by human rights treaty bodies. The growing awareness of the environment has already yielded considerable legislative and regulatory output. However, the implementation of standards remains a pervasive problem. In the fight against violations of norms, citizens have a crucial role to play. We discuss the relevance of a yet to be proclaimed standalone right to a healthy environment. PMID- 26162354 TI - The yield of a tuberculosis household contact investigation in two regions of Ethiopia. AB - SETTING: Amhara and Oromia regions, Ethiopia. OBJECTIVE: To determine the yield of a household contact investigation for tuberculosis (TB) under routine programme conditions. DESIGN: Between April 2013 and March 2014, TB clinic officers conducted symptom-based screening for household contacts (HHCs) of 6015 smear-positive TB (SS+ TB) index cases. Based on quarterly reported programme data, we calculated the yield in terms of number needed to screen (NNS) and number needed to test (NNT). RESULTS: Of 15,527 HHCs screened, 6.1% had presumptive TB (8.5% in Oromia vs. 3.9% in Amhara). All forms of TB and SS+ TB were diagnosed in respectively 2.5% (Oromia 3.9% vs. Amhara 1.2%) and 0.76% (Oromia 0.98% vs. Amhara 0.55%) of contacts. The NNS to detect a TB case all forms and SS+ TB was respectively 40 and 132. The NNT to diagnose a TB case all forms and SS+ TB was respectively 2.4 and 8. Of 1687 eligible children aged <5 years, 323 were started on isoniazid preventive therapy. CONCLUSIONS: The yield of the household contact investigation was over 10 times higher than the estimated prevalence in the general population; household contact investigations can serve as an entry point for childhood TB care. PMID- 26162356 TI - Pathways and costs of care for patients with tuberculosis symptoms in rural Uganda. AB - SETTING: Six district-level government health centers in rural Uganda and the surrounding communities. OBJECTIVE: To determine pathways to care and associated costs for patients with chronic cough referred for tuberculosis (TB) evaluation in Uganda. DESIGN: We conducted a cross-sectional study, surveying 64 patients presenting with chronic cough and undergoing first-time sputum evaluation at government clinics. We also surveyed a random sample of 114 individuals with chronic cough in surrounding communities. We collected information on previous health visits for the cough as well as costs associated with the current visit. RESULTS: Eighty per cent of clinic patients had previously sought care for their cough, with a median of three previous visits (range 0-32, interquartile range [IQR] 2-5). Most (n = 203, 88%) visits were to a health facility that did not provide TB microscopy services, and the majority occurred in the private sector. The cost of seeking care for the current visit alone represented 28.8% (IQR 9.1 109.5) of the patients' median monthly household income. CONCLUSION: Most patients seek health care for chronic cough, but do so first in the private sector. Engagement of the private sector and streamlining TB diagnostic evaluation are critical for improving case detection and meeting global TB elimination targets. PMID- 26162357 TI - The validity of three sputum smears taken in one day for discontinuing isolation of tuberculosis patients. AB - We conducted a retrospective comparative study of acid-fast bacilli (AFB) smear sensitivity according to time of specimen collection to assess whether three consecutive AFB smears collected in 1 day are useful when deciding to discontinue respiratory isolation of patients with pulmonary tuberculosis (TB). A total of 236 sputum specimens from 119 patients with pulmonary TB were used for the analysis. There was no statistical difference in AFB smear sensitivity of early morning sputum and those collected later (P = 0.186). This may allow us to collect all specimens in a single day and discontinue respiratory isolation of TB patients earlier. PMID- 26162358 TI - Overview of the tuberculosis burden in prison institutions in Japan, 2000-2012. AB - BACKGROUND: Although prison inmates in Japan are considered a high-risk group for tuberculosis (TB), little is known about the overall TB burden in prisons. OBJECTIVE: To estimate the incidence and epidemiological characteristics of TB among inmates in Japan, and to perform an ecological analysis to identify an association between socio-economic factors and TB incidence in prisons. METHOD: Using the annual reports on correctional statistics, we calculated TB incidence among inmates between 2000 and 2012. Multivariate analysis was conducted with selected socio-economic variables to examine their impact on overall and age specific incidence. RESULTS: The average TB incidence between 2000 and 2012 among inmates was 255.0 per 100,000 population. The proportion of foreigners among new inmates was the best predictor of overall TB incidence, as well as of incidence among inmates aged 20-29 and 30-39 years. The proportion of those working in the construction industry before being arrested was the best predictor of incidence among those aged 40-49 and 50-59 years. CONCLUSION: TB incidence among inmates was approximately 11 times higher than in the general population. A more detailed analysis of patient information is needed to identify specific risk groups within the incarcerated population and improve case finding. PMID- 26162355 TI - Vitamin D deficiency in Malawian adults with pulmonary tuberculosis: risk factors and treatment outcomes. AB - SETTING: Vitamin D deficiency is common in African adults with tuberculosis (TB), and may be exacerbated by the metabolic effects of anti-tuberculosis drugs and antiretroviral therapy (ART). It is unclear whether vitamin D deficiency influences response to anti-tuberculosis treatment. OBJECTIVES: To describe risk factors for baseline vitamin D deficiency in Malawian adults with pulmonary TB, assess the relationship between serum 25-hydroxy vitamin D (25[OH]D) concentration and treatment response, and evaluate whether the administration of anti-tuberculosis drugs and ART is deleterious to vitamin D status during treatment. DESIGN: A prospective longitudinal cohort study. RESULTS: The median baseline 25(OH)D concentration of the 169 patients (58% human immunodeficiency virus [HIV] infected) recruited was 57 nmol/l; 47 (28%) had vitamin D deficiency (<50 nmol/l). Baseline 25(OH)D concentrations were lower during the cold season (P < 0.001), with food insecurity (P = 0.034) or in patients who consumed alcohol (P = 0.019). No relationship between vitamin D status and anti-tuberculosis treatment response was found. 25(OH)D concentrations increased during anti tuberculosis treatment, irrespective of HIV status or use of ART. CONCLUSIONS: Vitamin D deficiency is common among TB patients in Malawi, but this does not influence treatment response. Adverse metabolic effects of drug treatment may be compensated by the positive impact of clinical recovery preventing exacerbation of vitamin D deficiency during anti-tuberculosis treatment. PMID- 26162359 TI - CD4 T-cell cytokine correlates of diagnostic tests for latent tuberculous infection in HIV-1-infected subjects. AB - SETTING: Public human immunodeficiency virus (HIV) clinic and tuberculosis (TB) clinics in Kampala, Uganda. OBJECTIVE: To examine TB-specific CD4 T-cell single and polyfunctional cytokine correlates of clinical diagnostic tests for latent tuberculous infection (LTBI) in HIV-1-infected subjects. DESIGN: Thirty antiretroviral therapy-naive HIV-1-infected adults without active TB disease underwent clinical tuberculin skin test (TST), interferon-gamma release assay (IGRA), and in vitro flow cytometry analysis on cells stimulated with purified protein derivative (PPD) and TB antigens early secreted antigenic target 6 + culture filtrate protein 10 (EC) for frequencies of interleukin (IL) 2, IL-17, interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) expressing cells. RESULTS: PPD-specific CD4 T-cell expression of TNF-alpha and IFN-gamma was higher in the TST-positive than in the TST-negative group. EC specific CD4 T-cell expression of TNF-alpha and IL-2 was higher in the TST+ group than in the TST- group. Expression of both PPD and EC-specific expression of IL 2, IFN-gamma and TNF-alpha were greater in IGRA-positive than in IGRA-negative subjects. The TST+ group exhibited greater polyfunctionality than the TST- group. All cytokine combinations that contained TNF-alpha correlated strongly with TST size. CONCLUSION: While IL-2, IFN-gamma and TNF-alpha correlate with clinical tests of LTBI, TNF-alpha is the dominant cytokine correlating with both TST size and magnitude of IGRA response. PMID- 26162360 TI - Risk of incident active tuberculosis and use of corticosteroids. AB - OBJECTIVE: To examine the association between corticosteroid use and risk of active tuberculosis (TB) disease. METHODS: We conducted a population-based nested case-control study based on Taiwan's National Health Insurance Research Database between January 1999 and December 2011. Each case of incident active TB was matched to 100 controls using a risk-set sampling scheme. RESULTS: From a participant cohort of 1 million, 6229 cases of new active TB and 622,900 controls were identified. Current, recent, past, ever and chronic use of corticosteroids were associated with an increased risk of developing incident active TB, with adjusted rate ratios of respectively 2.76 (95%CI 2.44-3.11), 1.99 (95%CI 1.73 2.31), 1.17 (95%CI 1.06-1.29), 1.60 (95%CI 1.49-1.72), and 1.58 (95%CI 1.43 1.75). For subgroup analysis, the increased risk of TB in chronic corticosteroids users was substantially higher in subjects aged <=70 years and female subjects. CONCLUSION: In this relatively high TB prevalence setting, we found that use of corticosteroids was associated with an increased risk of TB. Current use of corticosteroids was associated with the highest risk of TB. PMID- 26162361 TI - HIV counseling and testing in tuberculosis contact investigations in the United States and Canada. AB - BACKGROUND: Determining the human immunodeficiency virus (HIV) status of tuberculosis (TB) patients and contacts is important. Despite existing guidelines, not all patients are tested, and testing of contacts is rarely performed. METHODS: In a study conducted at nine US/Canadian sites, we introduced formal procedures for offering HIV testing to TB patients and contacts. Data were collected via interviews and medical record review. Characteristics associated with offering and accepting HIV testing were examined. RESULTS: Of 651 TB patients, 601 (92%) were offered testing, 511 (85%) accepted, and 51 (10%) were HIV-infected. Of 4152 contacts, 3099 (75%) were offered testing, 1202 (39%) accepted, and 24 (2%) were HIV-infected. Contacts aged 15-64 years, non-Whites, foreign-born persons, smokers, those with positive TB screening, and household contacts were more likely to be offered testing, whereas contacts exposed to HIV negative patients were less likely to be offered testing. Contacts aged 15-64 years, smokers, drug/alcohol users, diabetics, and those with positive TB screening were more likely to accept testing. Foreign-born persons, Blacks, Hispanics, and contacts exposed to HIV-positive patients were less likely to accept testing. CONCLUSIONS: High rates of HIV were detected among patients and contacts. Despite structured procedures to offer HIV testing, some patients and most contacts did not accept testing. Strategies are needed to improve testing acceptance rates. PMID- 26162362 TI - Evaluation of GenoType MTBDRplus for the rapid detection of drug-resistant tuberculosis in Ghana. AB - BACKGROUND: Rapid but simple diagnostic tools for the detection of drug-resistant (DR) tuberculosis (TB) have been acknowledged as being important for its effective management and control. OBJECTIVE: To establish a molecular line-probe assay (GenoType MTBDRplus) for detecting DR-TB in Ghana. METHOD: We first screened 113 Mycobacterium tuberculosis isolates using the indirect proportion method and MTBDRplus. The rpoB and katG genes and the promoter regions of oxyR ahpC and inhA were sequenced to identify mutations in isolates found to be resistant on phenotypic drug susceptibility testing and/or MTBDRplus. We then analysed an additional 412 isolates using only MTBDRplus. RESULTS: Respectively 43 (8.2%) and 8 (1.5%) isolates were resistant to isoniazid (INH) and rifampicin (RMP), while 8 (1.5%) were multidrug-resistant. In resistant isolates, mutations in codon 450 of rpoB and codon 315 of katG, conferring resistance to respectively RMP and INH, dominated. We found two RMP-resistant isolates with a S450L substitution, each harbouring an additional mutation at S388L and Q409R. Using phenotypic testing as gold standard, the MTBDRplus assay showed a sensitivity and specificity in the detection of RMP and INH resistance and multidrug resistance of respectively 100% and 100%, 83.3% and 100%, and 100% and 100%. CONCLUSION: The high sensitivity of MTBDRplus makes it a valuable addition to the conventional TB diagnostic algorithm in Ghana. PMID- 26162363 TI - Comparing multidrug-resistant tuberculosis patient costs under molecular diagnostic algorithms in South Africa. AB - SETTING: Ten primary health care facilities in Cape Town, South Africa, 2010 2013. OBJECTIVE: A comparison of costs incurred by patients in GenoType MDRTBplus line-probe assay (LPA) and Xpert MTB/RIF-based diagnostic algorithms from symptom onset until treatment initiation for multidrug-resistant tuberculosis (MDR-TB). METHODS: Eligible patients identified from laboratory and facility records were interviewed 3-6 months after treatment initiation and a cost questionnaire completed. Direct and indirect costs, individual and household income, loss of individual income and change in household income were recorded in local currency, adjusted to 2013 costs and converted to $US. RESULTS: Median number of visits to initiation of MDR-TB treatment was reduced from 20 to 7 (P < 0.001) and median costs fell from US$68.1 to US$38.3 (P = 0.004) in the Xpert group. From symptom onset to being interviewed, the proportion of unemployed increased from 39% to 73% in the LPA group (P < 0.001) and from 53% to 89% in the Xpert group (P < 0.001). Median household income decreased by 16% in the LPA group and by 13% in the Xpert group. CONCLUSION: The introduction of an Xpert-based algorithm brought relief by reducing the costs incurred by patients, but loss of employment and income persist. Patients require support to mitigate this impact. PMID- 26162364 TI - Treatment outcomes for HIV and MDR-TB co-infected adults and children: systematic review and meta-analysis. AB - BACKGROUND: The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing in high human immunodeficiency virus (HIV) prevalence settings, with high associated mortality. Treatment outcomes in HIV-co-infected adults and children are poorly documented. OBJECTIVE: To systematically assess treatment outcomes among HIV-MDR-TB co-infected patients. METHODS: We searched two databases and the proceedings of an annual international conference up to November 2014 for studies reporting on major clinical outcomes among HIV-MDR-TB co-infected adults and children, and pooled the results using random-effects meta analysis. RESULTS: Of 4812 abstracts and articles screened, 30 studies providing data on 2578 adults and 147 children were included. Overall pooled treatment success was 56.9% (95% confidence interval [CI] 46.2-67.6), 49.9% (95%CI 38.5 61.2) among adults and 83.4% (95%CI 74.7-92) among children. Mortality was 38% in adults (95%CI 28-48.1) and 11.4% (95%CI 5.8-17.1) in children. Loss to follow-up was higher among adults (16.1%, 95%CI 9-23.2) than among children (3.9%, 95%CI 0.9-6.9). Adverse events were experienced by the majority of patients; however, this was inconsistently documented. The use of fluoroquinolones, aminoglycosides and Group IV drugs appeared to be associated with treatment success. CONCLUSION: The proportion of HIV-MDR-TB-co-infected patients achieving treatment success was similar to success rates reported among MDR-TB patients in general, regardless of HIV status; however, mortality was higher, particularly among adults, highlighting the need for early diagnosis and more effective treatment regimens. PMID- 26162365 TI - Treatment of drug-resistant tuberculosis with bedaquiline in a high HIV prevalence setting: an interim cohort analysis. AB - BACKGROUND: South Africa has a large burden of extensively drug-resistant tuberculosis (XDR-TB); only 15% of XDR-TB patients have successful outcomes. OBJECTIVE: To describe the safety and effectiveness of bedaquiline (BDQ) in the South African BDQ Clinical Access Programme. DESIGN: An interim cohort analysis. RESULTS: Of the first 91 patients enrolled between March 2013 and July 2014 (with follow-up until August 2014), 54 (59%) were human immunodeficiency virus (HIV) infected. The median CD4 count was 239 cells/MUl, and all patients were on antiretroviral therapy (ART) at initiation of BDQ; 33 had XDR-TB, 41 were pre-XDR TB with fluoroquinolone resistance and 17 were pre-XDR-TB with resistance to an injectable. Of the 91 patients, 58 (64%) had completed 24 weeks of BDQ, 28 were still on BDQ, 3 were lost to follow-up, 1 had died and 1 had BDQ withdrawn following atrial fibrillation. Of the 63 patients with 6 months follow-up, 48 (76%) had either culture-converted or remained culture-negative after initiation of BDQ. QTcF was monitored monthly and exceeded 500 ms in three participants; this resolved in all three. CONCLUSION: Interim safety and culture conversion outcomes for patients accessing BDQ in South Africa, including HIV-infected patients on ART and patients with pre-XDR- and XDR-TB, suggest that BDQ may be both efficacious and safe. PMID- 26162366 TI - Loop-mediated isothermal amplification as alternative to PCR for the diagnosis of extra-pulmonary tuberculosis. AB - BACKGROUND: The main challenge in combatting extra-pulmonary tuberculosis (EPTB) is the lack of a rapid, reliable and inexpensive diagnostic test for the detection of Mycobacterium tuberculosis. OBJECTIVE: To evaluate the diagnostic potential of an L-serine dehydratase gene (sdaA) loop-mediated isothermal amplification (LAMP) assay for the detection of M. tuberculosis in clinical specimens from presumptive EPTB patients. METHODS: An in-house sdaA LAMP assay was used to analyse clinical specimens (n = 315) for the diagnosis of EPTB compared with culture and the composite reference standard (CRS) comprising culture and polymerase chain reaction (PCR) using insertion sequence (IS) 6110 and mpb64 as target genes. RESULTS: The sdaA LAMP assay showed the highest sensitivity (93.3%) in comparison to culture; the sensitivity of IS6110 PCR, mpb64 and sdaA PCR assay was respectively 80%, 86.7% and 90%. In comparison to CRS, the LAMP assay had a sensitivity of 92.5% and a specificity of 99.2%, with a high positive (121.11) and a low negative likelihood ratio (0.08). CONCLUSION: Due to its speed, simplicity, sensitivity and specificity, the sdaA LAMP assay is a potential diagnostic test for the diagnosis of EPTB, particularly in resource limited settings. PMID- 26162367 TI - Frequency and characteristics of different clinical phenotypes of chronic obstructive pulmonary disease. AB - SETTING: Clinical phenotypes of chronic obstructive pulmonary disease (COPD) identify patients with common characteristics. OBJECTIVES: To investigate the distribution of four different COPD phenotypes: non-exacerbators, patients with asthma-COPD overlap syndrome (ACOS), exacerbators with chronic bronchitis and those without, we analysed the impact of COPD on quality of life (HRQoL), and on anxiety and depression in these phenotypes. DESIGN: Observational, multicentre study conducted among 3125 COPD patients recruited from out-patient clinics in Barcelona, Spain. Phenotyping was performed based on the clinical information available. The COPD Assessment Test and EuroQoL-5 Dimensions questionnaire were used to evaluate HRQoL; patient mood was evaluated using the Hospital Anxiety and Depression Scale (HADS). RESULTS: The distribution of phenotypes was as follows: 60.6% non-exacerbators, 15.9% ACOS patients, 19.3% exacerbators with chronic bronchitis and 4.3% exacerbators without chronic bronchitis. Non-exacerbators had milder COPD, whereas exacerbators presented with the most severe disease, with little difference between those with and those without chronic bronchitis. ACOS patients were more frequently female with better lung function, but more impaired HRQoL and greater anxiety and depression, than non-exacerbators. CONCLUSIONS: Almost two thirds of COPD patients are non-exacerbators, and 15.9% have ACOS. Different phenotypes showed different demographic and clinical characteristics as well as impact on HRQoL and mood. PMID- 26162368 TI - A rare cause of osteomyelitis with a rare genetic mutation: when Mycobacterium doesn't only mean tuberculosis. PMID- 26162370 TI - The nature of evidence for and against epigenetic inheritance. AB - Not so fast. The Iqbal et. al. study and the associated Whitelaw commentary highlight the appropriately high standards of study design and interpretation needed to obtain good evidence for or against epigenetic inheritance. Please see related article: www.dx.doi.org/10.1186/s13059-015-0714-1. PMID- 26162369 TI - Understanding barriers to optimal medication management for those requiring long term dialysis: rationale and design for an observational study, and a quantitative description of study variables and data. AB - BACKGROUND: Rates of medication non-adherence in dialysis patients are high, and improving adherence is likely to improve outcomes. Few data are available regarding factors associated with medication adherence in dialysis patients, and these data are needed to inform effective intervention strategies. METHODS/DESIGN: This is an observational cross-sectional study of a multi-ethnic dialysis cohort from New Zealand, with the main data collection tool being an interviewer-assisted survey. A total of 100 participants were randomly sampled from a single centre, with selection stratified by ethnicity and dialysis modality (facility versus home). The main outcome measure is self-reported medication adherence using the Morisky 8-Item Medication Adherence Scale (MMAS 8). Study data include demographic, clinical, social and psychometric characteristics, the latter being constructs of health literacy, medication knowledge, beliefs about medications, and illness perceptions. Psychometric constructs were assessed through the following survey instruments; health literacy screening questions, the Medication Knowledge Evaluation Tool (Okuyan et al.), the Beliefs about Medication Questionnaire (Horne et al.), the Brief Illness Perception Questionnaire (Broadbent et al.). Using the study data, reliability analysis for internal consistency is satisfactory for the scales evaluating health literacy, medication knowledge, and beliefs about medications, with Chronbach's alpha > 0.7 for all. Reliability analysis indicated poor internal consistency for scales relating to illness perceptions. MMAS-8 and all psychometric scores are normally distributed in the study data. DISCUSSION: This study will provide important information on the factors involved in medication non-adherence in New Zealand dialysis patients. The resulting knowledge will inform long-term initiatives to reduce medication non-adherence in dialysis patients, and help ensure that they are addressing appropriate and evidence based targets for intervention. PMID- 26162372 TI - Preclinical Positron Emission Tomographic Imaging of Acute Hyperoxia Therapy of Chronic Hypoxia during Pregnancy. AB - The goal of this work was to study the efficacy of the positron emission tomography (PET) tracers 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 64Cu diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]ATSM) and in monitoring placental and fetal functional response to acute hyperoxia in late-term pregnant mice subjected to experimentally induced chronic hypoxia. E15 mice were maintained at 12% inspired oxygen for 72 hours and then imaged during oxygen inhalation with either [18F]FDG to monitor nutrient transport or 64Cu-ATSM to establish the presence of hypoxia. Computed tomography (CT) with contrast allowed clear visualization of both placentas and fetuses. The average ratio of fetal to placental [18F]FDG uptake was 0.45 +/- 0.1 for the hypoxic animals and 0.55 +/- 0.1 for the normoxic animals, demonstrating a significant decrease (p = .0002) in placental function in dams exposed to chronic hypoxic conditions. Hypoxic placentas and fetuses retained more 64Cu-ATSM compared to normoxic placentas and fetuses. Herein we report first-in-mouse PET imaging of fetuses employing both tracers [18F]FDG (metabolism) and 64Cu-ATSM (hypoxia). [18F]FDG PET/CT imaging allowed clear visualization of placental-fetal structures and supported quantification of tracer uptake, making this a sensitive tool for monitoring placental function in preclinical rodent models. These measurements illustrate the potentially irreversible damage generated by chronic exposure to hypoxia, which cannot be corrected by acute exposure to hyperoxia. PMID- 26162371 TI - Association of hypertension with physical factors of wrist pulse waves using a computational approach: a pilot study. AB - BACKGROUND: The objectives of this pilot study were to examine the association between hypertension and physical factors of wrist pulse waves to avoid subjective diagnoses in Traditional Chinese Medicine (TCM) and Traditional Korean Medicine (TKM). An additional objective was to assess the predictive power of individual and combined physical factors in order to identify the degree of agreement between diagnosis accuracies using physical factors and using a sphygmomanometer in the prediction of hypertension. METHODS: In total, 393 women aged 46 to 73 years participated in this study. Logistic regression (LR) and a naive Bayes algorithm (NB) were used to assess statistically significant differences and the predictive power of hypertension, and a wrapper-based machine learning method was used to evaluate the predictive power of combinations of physical factors. RESULTS: In both wrists, L-PPI and R-PPI (maximum pulse amplitudes in the left Gwan and right Gwan) were the factors most strongly associated with hypertension after adjusting for age and body mass index (p = <0.001, odds ratio (OR) = 2.006 on the left and p = <0.001, OR = 2.504 on the right), and the best predictors (NB-AUC = 0.692, LR-AUC = 0.7 on the left and NB AUC = 0.759, LR-AUC = 0.763 on the right). Analyses of both individual and combined physical factors revealed that the predictive power of the physical factors in the right wrist was higher than for the left wrist. The predictive powers of the combined physical factors were higher than those of the best single predictors in both the left and right wrists. CONCLUSION: We suggested new physical factors related to the sum of the area on the particular region of pulse waves in both wrists. L-PPI and R-PPI among all variables used in this study were good indicators of hypertension. Our findings support the quantification and objectification of pulse patterns and disease in TCM and TKM for complementary and alternative medicine. PMID- 26162373 TI - Analysis of employment rate and social status in young adults with childhood onset rheumatic disease in Catalonia. AB - BACKGROUND: Rheumatic diseases of childhood, in particular juvenile idiopathic arthritis, are chronic conditions associated with considerable morbidity and mortality that can have repercussions on aspects of adult life. The aim of this study was to determine the employment rate and social status of patients with childhood-onset rheumatic disease attending a pediatric rheumatology transition unit. METHODS: A census was taken of patients seen in the Pediatric Rheumatology Transition Unit of Hospital Vall d'Hebron (Barcelona, Spain). We collected demographic and clinical variables and determined the patients' functional capacity. All patients seen during the period of September to December 2013 underwent a survey containing items related to their social situation, maximum academic level achieved, and working life. Correlations were sought between clinical variables associated with a poor prognosis and the patients' job performance. The data were analyzed and compared with those of an age-matched cohort from the general population of Catalonia. RESULTS: Of 130 patients included in the census, 96 responded to the survey. Steinbrocker grade III and IV disability (poorer functional capacity) (p = 0.0025) and longer disease duration (p = 0.017) were significantly related to greater difficulty getting a job. Patients with grade III and IV disability and those with more severe disease showed trends to having more problems carrying out work-related tasks. Our cohort included a higher percentage of students than the age-matched comparison population (50 % vs 24 %, respectively) (p = 0.0001); 82 % of patients had completed studies beyond the compulsory education level. The employment rate was lower in our patient cohort than in the comparison cohort (38.3 % vs 59.9 %) (p = 0.0001), whereas the percentage of unemployed was similar. Patients with milder disease had a higher probability of living with their parents up to a later age (OR = 3.2, 95 % CI 0.38-6.15; p = 0.029). CONCLUSIONS: Despite the advances in treatment, some patients with childhood-onset rheumatic disease encounter difficulties in their later social and working life. In our cohort, the time period needed to complete their studies tended to be longer, and incorporation into the workforce occurred at a later age. Our findings reinforce the idea that psychological support and vocational guidance are important factors in the management of these patients. PMID- 26162374 TI - Optimizing strategies for population-based chlamydia infection screening among young women: an age-structured system dynamics approach. AB - BACKGROUND: Chlamydia infection (CT) is one of the most commonly reported sexually transmitted diseases. It is often referred to as a "silent" disease with the majority of infected people having no symptoms. Without early detection, it can progress to serious reproductive and other health problems. Economical identification of asymptomatically infected is a key public health challenge. Increasing evidence suggests that CT infection risk varies over the range of adolescence. Hence, age-dependent screening strategies with more frequent testing for certain age groups of higher risk may be cost-saving in controlling the disease. METHODS: We study the optimization of age-dependent screening strategies for population-based chlamydia infection screening among young women. We develop an age-structured compartment model for CT natural progress, screening, and treatment. We apply parameter optimization on the resultant PDE-based system dynamical models with the objective of minimizing the total care spending, including screening and treatment costs during the program period and anticipated costs of treating the sequelae afterwards). For ease of practical implementation, we also search for the best screening initiation age for strategies with a constant screening frequency. RESULTS: The optimal age-dependent strategies identified outperform the current CDC recommendations both in terms of total care spending and disease prevalence at the termination of the program. For example, the age-dependent strategy that allows monthly screening rate changes can save about 5% of the total spending. Our results suggest early initiation of CT screening is likely beneficial to the cost saving and prevalence reduction. Finally, our results imply that the strategy design may not be sensitive to accurate quantification of the age-specific CT infection risk if screening initiation age and screening rate are the only decisions to make. CONCLUSIONS: Our research demonstrates the potential economic benefit of age-dependent screening strategy design for population-based screening programs. It also showcases the applicability of age-structured system dynamical modeling to infectious disease control with increasing evidence on the age differences in infection risk. The research can be further improved with consideration of the difference between first-time infection and reinfection, as well as population heterogeneity in sexual partnership. PMID- 26162376 TI - Downside of becoming a richer country. PMID- 26162377 TI - Effects of acute chemotherapy-induced mucositis on spontaneous behaviour and the grimace scale in laboratory rats. AB - Intestinal mucositis is a frequent side-effect of chemotherapy treatment. Many oncological research programs aim to identify novel treatments for this distressing condition, and these programs frequently use rat models. Little is known about the presence and progression of pain in these models and how this can best be treated by analgesic therapy. We used a number of behaviour-based methods of pain assessment to determine which tools were best suited for pain identification. Baseline measures for behavioural assessment, rat grimace score and sociability were determined through analysis of continuously recorded video data and an applied social interaction test (n = 16). Mucositis was then induced by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and further behavioural analyses undertaken. An assessment of enrichment interaction was also made by determining the mass of a plastic chew toy gnawed both pre- and post chemotherapy injection. Behavioural scoring was performed 1, 6, 12, 24 and 48 h after injection, with facial expression being scored at the 12, 24 and 48 h time points. Sociability testing was performed once during the post-injection period. No significant differences were found in grimace scores between baseline and later daily measures. Behaviours similar to those previously reported post laparotomy were observed. Writhing, twitching and back-arching behaviours were most evident in rats affected by mucositis and were increased in frequency (respective P values: 0.002, 0.004 and 0.008) 48 h after chemotherapy injection compared with baseline, implying that pain onset occurred around this time-point. Social investigatory behaviour was also increased (P = 0.002) following disease onset. Each day, rats post-5FU injection gnawed a greater percentage of their Nylabone enrichment by weight than the saline-injected control rats (P = 0.046). These data suggest that, of the tools tested, behavioural assessment scoring may find greatest utility in rodent models of intestinal mucositis and should be investigated further. PMID- 26162375 TI - Drosophila anti-nematode and antibacterial immune regulators revealed by RNA-Seq. AB - BACKGROUND: Drosophila melanogaster activates a variety of immune responses against microbial infections. However, information on the Drosophila immune response to entomopathogenic nematode infections is currently limited. The nematode Heterorhabditis bacteriophora is an insect parasite that forms a mutualistic relationship with the gram-negative bacteria Photorhabdus luminescens. Following infection, the nematodes release the bacteria that quickly multiply within the insect and produce several toxins that eventually kill the host. Although we currently know that the insect immune system interacts with Photorhabdus, information on interaction with the nematode vector is scarce. RESULTS: Here we have used next generation RNA-sequencing to analyze the transcriptional profile of wild-type adult flies infected by axenic Heterorhabditis nematodes (lacking Photorhabdus bacteria), symbiotic Heterorhabditis nematodes (carrying Photorhabdus bacteria), and Photorhabdus bacteria alone. We have obtained approximately 54 million reads from the different infection treatments. Bioinformatic analysis shows that infection with Photorhabdus alters the transcription of a large number of Drosophila genes involved in translational repression as well in response to stress. However, Heterorhabditis infection alters the transcription of several genes that participate in lipidhomeostasis and metabolism, stress responses, DNA/protein synthesis and neuronal functions. We have also identified genes in the fly with potential roles in nematode recognition, anti-nematode activity and nociception. CONCLUSIONS: These findings provide fundamental information on the molecular events that take place in Drosophila upon infection with the two pathogens, either separately or together. Such large-scale transcriptomic analyses set the stage for future functional studies aimed at identifying the exact role of key factors in the Drosophila immune response against nematode-bacteria complexes. PMID- 26162379 TI - Internal Jugular Vein Height and Inferior Vena Cava Diameter Measurement using Ultrasound to Determine Central Venous Pressure: A Correlation Study. AB - OBJECTIVE: To determine the correlation between central venous pressure (CVP) measured by conventional central venous access and ultrasonographic measurement of internal jugular vein (IJV) height and inferior vena cava (IVC) diameter. METHODS: A prospective, cross-sectional, convenience sampling observational study. RESULTS: 25 patients from the Emergency Department (ED) Universiti Kebangsaan Malaysia Medical Centre (UKMMC) were studied between 1st March and 30th April 2013. The median age was 63 years (95% CI 54-67). There was a significant correlation between IJV height and CVP using central venous access (r=0.64 p<0.001). Correlation between IVC diameter in end expiration and CVP was 0.74 (p<0.001). An IJV height measurement >8cm predicted a CVP >8cm H2O (sensitivity 71.4%, specificity of 83.3%). CONCLUSION: Measurement of IJV height and IVC diameter by ultrasonography correlates well with invasive CVP and is useful for the assessment of volume status in critically ill patients in the ED. PMID- 26162378 TI - Identification of four new degradation products of epirubicin through forced degradation, LC-UV, MSn and LC-MS-TOF studies. AB - Epirubicin (EPI) was subjected to International Conference on Harmonization recommended forced degradation under the conditions of hydrolysis, oxidation, dry heat and photolysis to characterize its possible impurities and/or degradation products. The drug was found highly unstable to alkaline hydrolysis even at room temperature, unstable to acid hydrolysis at 80 degrees C and to oxidation at room temperature. The hydrolytic and oxidative degradation products were resolved on an Agilent RP8 (150 mm * 4.6 mm; 5 um) column with isocratic elution using mobile phase composed of ammonium formate (10 mM, pH 3.0), acetonitrile and methanol. The drug degraded to four oxidative products (O-I, O-II, O-III and O-IV) and to one acid hydrolyzed product (A-I). Purity of each peak in liquid chromatography ultraviolet (LC-UV) chromatogram was ascertained through photodiode array (LC PDA) analysis. The products were characterized through electrospray ionization mass spectrometry (+ESI-MS(n)) studies on EPI and liquid chromatography-time of flight mass spectrometry (LC-MS-TOF) studies on degraded drug solutions. The products, O-I-O-IV, were characterized as 2-hydroxy-8-desacetylepirubicin-8 hydroperoxide, 4-hydroxy-8-desacetylepirubicin-8-hydroperoxide, 8 desacetylepirubicin-8-hydroperoxide and 8-desacetylepirubicin, respectively, and product A-I was characterized as deglucosaminylepirubicin. While A-I was found to be a pharmacopoeial impurity, all oxidative products were found to be new degradation impurities. The mechanisms and pathways of degradation of EPI were discussed and outlined. PMID- 26162380 TI - Descriptive Review of Safety, Reactogenicity and Immunogenicity of Dengue Vaccine Clinical Trials, 2003 - 2013. AB - Dengue vaccine development has been one of the strategies to reduce dengue incidence in the world alongside with other horizontal interventions such as vector control and the transgenic mosquito programmes. The objective of this paper is to evaluate the safety, reactogenicity and immunogenicity of dengue vaccine clinical trials for the last ten years systematically through a descriptive review. This paper discusses safety issues like adverse events, systemic adverse reactions, injection site reactions, viraemia, morbidity and mortality as well as immunogenicity which measures effectiveness through mean geometric titre and seropositive rates. Adverse events were seen to range from 0% to 28.3%. Immunogenicity was noted to increase post 1st and 2nd dose and decrease post 3rd dose. The seropositivity at baseline ranged between 53.1% and 97.8% at post 3rd dose, and it was 88.5% for at least four serotypes. The dengue vaccine studies that were reviewed were shown to be relatively safe with low reactogenicity, however the immunogenicity was unequal and waning. The immunogenicity waned post 3rd dose showing a decrease in all serotypes of varying degrees although the seropositivity, on average, at post 3rd dose was 97.8%. It can be concluded that dengue vaccine development would require further studies on its unequal and waning immunogenicity, which could result in a more severe form of dengue following wild infection, during re-immunisation, especially if there is variation in the circulating virus. PMID- 26162381 TI - Malaysian Medical Students' self-reported Empathy: A cross-sectional Comparative Study. AB - OBJECTIVES: The objective of this study was to compare empathy levels between first year and second year medical students at a Malaysian University. SETTING: A Malaysian University offering undergraduate medicine. PARTICIPANTS: 204 undergraduate medical students were included in the data analysis (122 first years, and 102 second years). MAIN OUTCOME MEASURE: Self-reported empathy scores using the Jefferson Scale of Physician Empathy (Student Version) JSPE-S. RESULTS: The mean empathy score for first year students was 112.1(SD=10.7). This was significantly higher (p<0.038; d=0.31) than second year students (mean=108.8, SD=10.4). No significant difference relating to gender was identified. CONCLUSION: Cross-sectional results from this study found that that there were differences in self-reported empathy scores between year one and year two students. Further research is required to ascertain if these differences are maintained as students' progress thought their medical degree, and whether other factors such as internships, medical rotations or clinical supervision have any impact of medical students' empathy levels. PMID- 26162382 TI - The Association Between Bullous Pemphigoid and Neurological Disorders in A Selected Malaysian Population. AB - BACKGROUND: An association of bullous pemphigoid with neurological disorders has been reported. The objectives of this study were to review the clinical characteristics of patients with bullous pemphigoid and compare the association between bullous pemphigoid and various neurological disorders and comorbidities. METHODS: This was a retrospective case-control study involving 43 patients with bullous pemphigoid and 43 age-, sex- and ethnicity-matched controls. RESULTS: There was a statistically significant association between bullous pemphigoid and neurological disorders [Odds Ratio (OR) = 3.5, 95% Confidence Interval (CI) 1.3 to 9.2, p=0.011 and adjusted OR=3.5, 95% CI 1.2-10.3, p=0.026], in particular for dementia (p=0.002). Although stroke was more common among patients with bullous pemphigoid, this association was not statistically significant with OR of 1.9 (95% CI 0.7 to 5.2) and adjusted OR of 2.1 (95% CI 0.6 to 7.2). Similarly both ischaemic stroke (OR 1.5, 95% CI 0.5 to 4.2) and haemorrhagic stroke (OR 1.5, 95% CI 0.2 to 9.7) were more common. Other neurological disorders more common among patients with bullous pemphigoid were Parkinson's disease and epilepsy. Dyslipidaemia was significantly less common among patients with bullous pemphigoid (OR 0.4, 95% CI 0.1 to 0.9, p=0.033). CONCLUSION: A combination of an inflammatory process, prothrombotic state and endothelial activation leads to an increased frequency of neurological disorders among patients with bullous pemphigoid. Thus, a holistic approach to patient care, including screening for dementia and control of comorbidities, should be practised as bullous pemphigoid affects more than just the skin. PMID- 26162383 TI - Traditional and Complementary Medicine (TCM) among Study Population with Cardiovascular Risk; use and Substitution for Conventional Medicine in Pahang, Malaysia. AB - INTRODUCTION: Cardiovascular diseases are the main cause of morbidity and mortality in Malaysia. There is evidence of high traditional and complementary medicine (TCM) use among population with cardiovascular risk and there have been anecdotal reports about substitution of conventional medicines with TCM. We investigated the prevalence of TCM use, treatment preference and substitution of conventional medicines in study population with cardiovascular risk factors in Pahang, Malaysia. METHODS: A cross-sectional survey was conducted using an interviewer-administered questionnaire in five districts of Pahang. A total of 1250 households were chosen through proportionate and systematic sampling. Respondents aged 18 years and above were selected. RESULTS: The study population with cardiovascular risk factors who used TCM was higher than the general population (31.7% versus 25.9%). There were no clear preferences in using TCM by gender, age groups, educational level and income even though other bumiputeras showed a slight inclination towards TCM use. Among the study population with cardiovascular risk factors who consumed TCM, 20-30% of them were using TCM as a substitute for their conventional medications. Respondents from the younger age group (18-40 years) (57.1%), highest educational level (43.2%), other bumiputeras (38.4%) and highest income group (31.4%) preferred the combination of both conventional and traditional medicine. CONCLUSION: TCM use among population with cardiovascular risk factors is high. The high preference for combination therapy of TCM and conventional medications among young adults and the use of TCM to substitute conventional medications show that much research is needed to provide proven TCM therapies to avoid self-mismanagement of cardiovascular risk in Malaysia. PMID- 26162384 TI - Chest Radiograph Findings In Novel Swine-Origin Influenza A (H1N1) Virus (S-OIV) Infection: A UKMMC Experience. AB - OBJECTIVE: 1.To evaluates and recognizes findings in chest radiograph in patients with laboratory-confirmed S-OIV (H1N1) infection treated at UKMMC. 2. To evaluate whether the findings on initial chest radiographs of influenza A (H1N1) patients can help to predict the prognosis. MATERIAL AND METHODS: Total of 109 adult patients presenting to the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) with flu-like symptoms who were positive for influenza A and these patients had underwent chest radiographs (CXR). The initial CXRs were evaluated for the pattern (consolidation, ground-glass, and reticulation), distribution, and extend of abnormality. The disease is classifies by the clinical severity (mild, moderate or severe illness) and adverse outcome (ventilated, death or recovered well). RESULTS: The initial CXRs were normal in 56% of cases. The predominant radiographic finding was consolidation, most commonly involving the middle and lower zones (35% of cases). There is no significant association between initial CXR findings with the patient clinical outcome either fully recovered or death/ ventilated. CONCLUSION: Normal chest radiographs is the most common radiographic finding in S-OIV (H1N1) infection and the most common abnormal lung finding is consolidation. Initial chest radiographs did not determine the patient clinical outcome and a normal initial radiograph could not exclude adverse outcome. PMID- 26162385 TI - A Rare Case of Retropharyngeal Hibernoma. AB - Hibernoma is a slow growing, rare benign tumour, which derived from brown adipose tissue. This tumour is usually found in the area where foetal fat persists such as back, axilla, retro peritoneum and thorax. Hibernoma rarely occurs in the retro pharynx. We report a case of retropharyngeal hibernoma in a 44-year-old male. He presented with obstructive symptoms for six months and a retropharyngeal mass upon examination. His CT scan findings showed a mass in the prevertebral region from level of C2 until C5 causing narrowing of upper aero digestive tract. Histopathological examination reported as hibernoma. PMID- 26162386 TI - Degenerated Retained Product of Conception Misdiagnosed as Invasive Trophoblastic Disease. AB - Retained products of conception (POC) complicates nearly 1% of all pregnancies, occurring with greater frequency after termination of pregnancy than after vaginal or caesarean delivery. The presenting symptoms of retained products of conception are similar to those of gestational trophoblastic disease and hence accurate differentiation is difficult based on clinical history and physical examination alone. The distinction between these two entities is extremely important as the treatment differs dramatically. These patients often need to be further evaluated with either ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis. Hence, radiologists play a vital role in clinching the diagnosis although at times it may be challenging to differentiate between these two entities. Herein, we discuss a case of degenerated retained products of conception which was initially misdiagnosed as invasive trophoblastic disease in a 41-year-old woman whom last known pregnancy was 10 years ago. PMID- 26162387 TI - Myxoid Neurofibromas of the External Ear Canal: A Case Report. AB - Myxoid neurofibroma is benign tumours of perineural cell origin that arise from elements in the peripheral nervous system. We report a case of a 60-year-old female patient presented with history of right ear mass which was slowly growing. Her primary complaint was cosmetic deformity but hearing loss was also present. The mass was excised and histologically revealed a myxoid neurofibroma. To the authors' knowledge, this is the first time that a myxoid neurofibroma arising from external auditory canal is reported. It should be included in the differential diagnosis of a mass originating from this location. PMID- 26162388 TI - Histoplasmosis with Addisonian Crisis: Call for Bird Control. AB - We report a case of disseminated histoplasmosis, initially diagnosed from gut nodule colonoscopically, along with evidence of lung disease. Subsequently he developed Addisonian crisis due to adrenal involvement. Lessons were learnt from the importance of detailed history-personal and social/family, as well as psychosocial aspects of illness. Public health measures to reduce bird dropping (and thus possibility of histoplasmosis) are discussed. PMID- 26162389 TI - Barlow's Repair: Light in the Dark Tunnel: A Case Report Could Omit 'Light in A Dark Tunnel'. AB - Barlow's disease has a complex pathology requiring reconstructive surgery. Despite the complicated surgery it holds a positive outcome. We report a successful case of Barlow's disease who underwent mitral valve reconstructive surgery at our centre. Post-operative echocardiography shows a well-functioning repaired mitral valve without significant mitral regurgitation. PMID- 26162390 TI - Combined Laparoscopic and Thoracoscopic Repair of A Large Traumatic Diaphragmatic Hernia: A Case Report. AB - Traumatic diaphragmatic hernia is a well known complication of blunt trauma to the abdomen and thorax. In the acute setting, laparotomy is mandatory. In this current era, this condition can be managed with minimally invasive surgery. We hereby report a case of delayed large left diaphragmatic hernia that was repaired with a combination of laparoscopic and thoracoscopic approach. PMID- 26162391 TI - A Case of Nasopharyngeal Carcinoma with Paraneoplastic Leukemoid Reaction: A Case Report. AB - We present a case of nasopharyngeal carcinoma complicated with hyperleucocytosis. After ruling our other causes we concluded that the hyperleucocytosis was due to paraneoplastic leukemoid reaction (PLR). The overall survival was 15 months which is rare among patients with PLR. PMID- 26162392 TI - Primary Sinonasal Clear Cell Carcinoma: Case Report. AB - Primary sinonasal clear cell carcinoma is a rare neoplasm classified under malignant epithelial tumours of salivary gland - type carcinomas under World Health Organization (WHO) classification. We report a case which occurred on a 69 year old gentleman presented with epistaxis and nasal endoscopy examination showed tumour arising from the right ethmoid cells. Endoscopic excision of the tumour was done and histopathological examination revealed clear cell carcinoma. In addition, other secondary or primary sites of the lesion were excluded by clinical, immunohistochemical and radiological examinations. 10 months into the postoperative period, patient remains well without recurrence of the tumour. IN CONCLUSION: We report a rare case of primary sinonasal clear cell carcinoma in addition to the limited literature available and emphasize the differentials with other probable tumour through meticulous microscopic examination and use of special immunostains. PMID- 26162393 TI - Suboptimal Therapy for Dyslipidaemia in Coronary Bypass Surgical Patients with Premature Ischaemic Heart Disease. AB - The incidence of premature multi-vessel coronary artery disease (CAD) is on the rise in Malaysia. The pathogenesis of coronary atherosclerosis is multi-factorial with dyslipidaemia being one such risk factor. Elevated total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels are primarily responsible. We analysed the fasting pre-operative lipid profiles of coronary artery bypass graft (CABG) patients with symptomatic severe premature CAD. A majority of patients had an elevated LDL cholesterol level despite being on a statin. Similarly, no patient with an elevated TG level was prescribed a fibrate. Pre-operative control of known dyslipidaemia was suboptimal in young adults with angiographially proven severe symptomatic CAD. This is either due to subtherapeutic dose prescribing or failure to commence appropriate anti-lipid drugs. Collectively, general practitioners, cardiologists and cardiac surgeons must be more diligent in monitoring lipid profiles in such patients and be more meticulous in prescribing therapeutic doses to achieve target control. PMID- 26162394 TI - Towards Mainstream Adoption of Tenecteplase for the Treatment of Acute Myocardial Infarction. AB - No abstract available. PMID- 26162395 TI - Outcomes from the Malaysian Arm of The International Survey Informing Greater Insights in Opioid Dependence Treatment (INSIGHT) Project. AB - BACKGROUND: Opioid dependence (OD) is a chronic, relapsing condition representing a significant societal burden in Asia. Opioid maintenance treatment (OMT) in combination with psychosocial treatment is considered to be the most effective strategy to treat opioid dependence. In Malaysia, about 52,000 patients reported receiving OMT in December 2012. OBJECTIVE: The International Survey Informing Greater Insights in Opioid Dependence Treatment (INSIGHT) project aimed to assess aspects of OMT access and quality of care by surveying patients and users with opioid dependence, and healthcare professionals treating opioid-dependent patients. MATERIALS AND METHODS: Using a structured questionnaire, 50 patients who were currently receiving OMT (or had received OMT in the past 3 months) and 77 physicians were surveyed in Malaysia regarding the provision and quality of OMT. RESULTS: Patients were predominately male and in their thirties. Nearly all patients (98%) reported currently receiving methadone liquid; almost half (48%) reported ever having received psychosocial counselling and only 14% had ever received buprenorphine-naloxone in the past. Most physicians reported they were treating their patients with OMT (77% on methadone and 15% on buprenorphine naloxone), and 3% used psychosocial counselling alone. Although methadone maintenance doses were close to levels recommended by WHO guidelines, induction doses of methadone, and both induction and maintenance doses of buprenorphine were well below these levels in Malaysia. CONCLUSIONS: The findings suggest that OMT implementation in Malaysia can be improved by providing patients with more education on treatment options, better access to available treatments, including abuse-deterrent formulations, and psychosocial support. PMID- 26162396 TI - Primary Ureteral Thyroid Transcription Factor 1-Positive Small Cell Neuroendocrine Carcinoma: Case Report and Review of the Literature. AB - Upper urinary tract neoplasms comprise only 5% of urinary malignancies overall, the overwhelming majority showing an urothelial histology. Nonurothelial lesions represent 1.9% of upper tract neoplasms, and small cell carcinomas (SmCCs) only account for a minute fraction of them, with few cases reported in the literature to date. In the genitourinary tract, these lesions are most frequently found in the urinary bladder, where they tend to show a mixed histology with a characteristic small cell neuroendocrine component that is positive for chromogranin A, synaptophysin, and CD56 immunostains. Urinary SmCCs are almost invariably aggressive, with a propensity to infiltrate surrounding tissues and vascular structures. Unfortunately, clinical stage at presentation is often advanced, with early dissemination to lymph nodes or distant organs in a significant proportion of patients. For the most part, prognosis is dismal and can be predicted by the pathologic stage at diagnosis. Recently, new chemotherapeutic regimens have shown some potential benefit for the treatment of urinary SmCC, albeit not achieving curative results. Here we present the case of a 71-year-old male patient with a history of treated bladder urothelial carcinoma that presented with subacute flank pain and was diagnosed with a primary pure SmCC of the ureter. Besides the usual neuroendocrine immunomarkers, this tumor showed intense positivity for TTF-1 (thyroid transcription factor-1), a phenomenon that has been described for extrapulmonary SmCC of other locations. PMID- 26162397 TI - A Peripheral Dentinogenic Ghost Cell Tumor With Immunohistochemical Investigations and a Literature Review-Based Clinicopathological Comparison Between Peripheral and Central Variants. AB - The aim of the study was to present a peripheral dentinogenic ghost cell tumor (DGCT) and to describe clinicopathological differences between peripheral and central variants of the tumor using a selected literature review. The case report is based on a swelling present on the alveolar ridge of a 74-year-old edentulous denture wearer. The lesion was diagnosed as a peripheral DGCT after excluding the presence of a central lesion. Immunohistochemical investigations revealed similar cytokeratin expression pattern, with CK14 and MNF116 positivity in both the tumor and the surrounding surface epithelium. However, in contrast, CK19 expression was restricted to less than 5% of the tumor cells. A clinicopathological comparison was compiled using 30 cases of peripheral DGCTs (including the present lesion) and 16 cases of central DGCTs published over a period of 40 years. Accordingly, peripheral lesions were more often found in elderly denture wearers, in relation to mandibular gingiva and alveolar mucosa. None of the lesions had recurred after excision. In contrast, majority of the central lesions were common in younger individuals and showed a striking male predilection. It occurred equally on both jaws, while approximately 50% of the lesions gave rise to recurrences. In conclusion, similar cytokeratin expression in both the tumor and surface epithelium can be used to support oral surface epithelial origin, while CK14 positivity confirms the odontogenic derivation of the peripheral DGCT described in the report. In contrast to central DGCT, the peripheral DGCT is a distinct lesion with characteristic clinicopathological profile and nonaggressive behavior. PMID- 26162398 TI - A traits-based test of the home-field advantage in mixed-species tree litter decomposition. AB - BACKGROUND AND AIMS: Litter often decomposes faster in its environment of origin (at 'home') than in a foreign environment ('away'), which has become known as the home-field advantage (HFA). However, many studies have highlighted the conditional nature of the HFA, suggesting that current understanding of this phenomenon is not yet sufficient to generalize across systems. METHODS: The HFA hypothesis was tested for mono-specific and mixed-species litter using a tree based experiment that manipulated the functional identity and diversity of the host tree community. Litter types of varying quality were transplanted between several host tree communities and decomposition rates were measured using litterbags. Since the decomposer community should respond to traits of the litter input and not their taxonomic identity, a traits-based index of litter-tree similarity was developed. KEY RESULTS: Mono-specific litter exhibited HFA, but when the same litter was decomposed in mixture, this trend was not observed. Mixed-species litter decomposed on average no faster or slower than monoculture litter and exhibited both positive and negative species interactions. These non additive interactions of decomposition rates in mixture were influenced by the degree of similarity between litter and tree traits. Both synergistic and antagonistic interactions decreased in magnitude with increasing litter-tree similarity such that mixture rates were predictable from monocultures. CONCLUSIONS: The HFA occurred more strongly for mono-specific litter than for the litter types mixed together because interactions between species may have masked this effect. However, when expressed as a function of trait similarity between litters and tree communities, the HFA was not detected. PMID- 26162400 TI - Arterial Stiffness and Emerging Biomarkers: Still a Long Journey to Go. PMID- 26162399 TI - Phenotype of Arabidopsis thaliana semi-dwarfs with deep roots and high growth rates under water-limiting conditions is independent of the GA5 loss-of-function alleles. AB - BACKGROUND AND AIMS: The occurrence of Arabidopsis thaliana semi-dwarf accessions carrying inactive alleles at the gibberellin (GA) biosynthesis GA5 locus has raised the question whether there are pleiotropic effects on other traits at the root level, such as rooting depth. In addition, it is unknown whether semi dwarfism in arabidopsis confers a growth advantage under water-limiting conditions compared with wild-type plants. The aim of this research was therefore to investigate whether semi-dwarfism has a pleiotropic effect in the root system and also whether semi-dwarfs might be more tolerant of water-limiting conditions. METHODS: The root systems of different arabidopsis semi-dwarfs and GA biosynthesis mutants were phenotyped in vitro using the GROWSCREEN-ROOT image based software. Semi-dwarfs were phenotyped together with tall, near-related accessions. In addition, root phenotypes were investigated in soil-filled rhizotrons. Rosette growth trajectories were analysed with the GROWSCREEN-FLUORO setup based on non-invasive imaging. KEY RESULTS: Mutations in the early steps of the GA biosynthesis pathway led to a reduction in shoot as well as root size. Depending on the genetic background, mutations at the GA5 locus yielded phenotypes characterized by decreased root length in comparison with related wild type ones. The semi-dwarf accession Pak-3 showed the deepest root system both in vitro and in soil cultivation experiments; this comparatively deep root system, however, was independent of the ga5 loss-of-function allele, as shown by co segregation analysis. When the accessions were grown under water-limiting conditions, semi-dwarf accessions with high growth rates were identified. CONCLUSIONS: The observed diversity in root system growth and architecture occurs independently of semi-dwarf phenotypes, and is probably linked to a genetic background effect. The results show that there are no clear advantages of semi dwarfism at low water availability in arabidopsis. PMID- 26162401 TI - Abdominal Aortic Aneurysms, Peripheral Arterial Disease, and Carotid Artery Stenosis: Different Sides of the Same Coin? PMID- 26162403 TI - Differential accumulation and function of proinflammatory 6-sulfo LacNAc dendritic cells in lymph node and colon of Crohn's versus ulcerative colitis patients. AB - Human Slan DCs have been studied in patients with psoriasis, rheumatoid arthritis, cancer, and autoimmune diseases. In this study, we investigated the frequency, phenotype, and function of Slan DCs in blood, colon, as well as mLNs of patients with IBD. We first show that the frequency of circulating CD14(dull)Slan DCs was reduced in CD patients refractory to immunosuppressive drugs or TNF-alpha blockers relative to untreated CD, UC, and healthy subjects. In blood of CD patients, Slan DCs expressed CD172a, as detected by CD47 fusion protein binding, when compared with its lack of expression in control subjects. Next, we demonstrate that CD172a(+)Slan DCs that produced IL-1beta and TNF-alpha accumulated in mLNs and colons of CD patients. The CD172a(+)Slan DCs up-regulated their expression of CD14 in CD tissues and the proinflammatory cytokines were produced in CD14(bright)CD172a(+)Slan DCs. By contrast, no difference was noted in the frequency of Slan DCs between inflamed, noninflamed colonic mucosa of UC patients and control, non-IBD donors. Finally, the percentage of cytokine producing Slan DCs also augmented in response to TLR2 and NOD2 in in vitro stimulation in PBMCs of CD, but not UC, patients. In conclusion, we propose that proinflammatory CD14(bright)CD172a(+)Slan DCs are a distinguishing feature between CD and UC, as these cells accumulate uniquely in mLNs and colonic mucosa of CD patients. Thus, Slan DCs may contribute to CD immunopathogenesis. PMID- 26162404 TI - Diagnostic use of facial image analysis software in endocrine and genetic disorders: review, current results and future perspectives. AB - Cushing's syndrome (CS) and acromegaly are endocrine diseases that are currently diagnosed with a delay of several years from disease onset. Novel diagnostic approaches and increased awareness among physicians are needed. Face classification technology has recently been introduced as a promising diagnostic tool for CS and acromegaly in pilot studies. It has also been used to classify various genetic syndromes using regular facial photographs. The authors provide a basic explanation of the technology, review available literature regarding its use in a medical setting, and discuss possible future developments. The method the authors have employed in previous studies uses standardized frontal and profile facial photographs for classification. Image analysis is based on applying mathematical functions evaluating geometry and image texture to a grid of nodes semi-automatically placed on relevant facial structures, yielding a binary classification result. Ongoing research focuses on improving diagnostic algorithms of this method and bringing it closer to clinical use. Regarding future perspectives, the authors propose an online interface that facilitates submission of patient data for analysis and retrieval of results as a possible model for clinical application. PMID- 26162402 TI - Elucidation of monocyte/macrophage dynamics and function by intravital imaging. AB - Monocytes and macrophages are a diverse population of innate immune cells that play a critical role in homeostasis and inflammation. These cells are surveillant by nature and closely monitor the vasculature and surrounding tissue during states of health and disease. Given their abundance and strategic positioning throughout the body, myeloid cells are among the first responders to any inflammatory challenge and are active participants in most immune-mediated diseases. Recent studies have shed new light on myeloid cell dynamics and function by use of an imaging technique referred to as intravital microscopy (IVM). This powerful approach allows researchers to gain real-time insights into monocytes and macrophages performing homeostatic and inflammatory tasks in living tissues. In this review, we will present a contemporary synopsis of how intravital microscopy has revolutionized our understanding of myeloid cell contributions to vascular maintenance, microbial defense, autoimmunity, tumorigenesis, and acute/chronic inflammatory diseases. PMID- 26162405 TI - The ARMC5 gene shows extensive genetic variance in primary macronodular adrenocortical hyperplasia. AB - OBJECTIVE: Primary macronodular adrenal hyperplasia (PMAH) is a rare type of Cushing's syndrome (CS) that results in increased cortisol production and bilateral enlargement of the adrenal glands. Recent work showed that the disease may be caused by germline and somatic mutations in the ARMC5 gene, a likely tumor suppressor gene (TSG). We investigated 20 different adrenal nodules from one patient with PMAH for ARMC5 somatic sequence changes. DESIGN: All of the nodules were obtained from a single patient who underwent bilateral adrenalectomy. DNA was extracted by standard protocol and the ARMC5 sequence was determined by the Sanger method. RESULTS: Sixteen of 20 adrenocortical nodules harbored, in addition to what appeared to be the germline mutation, a second somatic variant. The p.Trp476* sequence change was present in all 20 nodules, as well as in normal tissue from the adrenal capsule, identifying it as the germline defect; each of the 16 other variants were found in different nodules: six were frame shift, four were missense, three were nonsense, and one was a splice site variation. Allelic losses were confirmed in two of the nodules. CONCLUSION: This is the most genetic variance of the ARMC5 gene ever described in a single patient with PMAH: each of 16 adrenocortical nodules had a second new, 'private,' and--in most cases- completely inactivating ARMC5 defect, in addition to the germline mutation. The data support the notion that ARMC5 is a TSG that needs a second, somatic hit, to mediate tumorigenesis leading to polyclonal nodularity; however, the driver of this extensive genetic variance of the second ARMC5 allele in adrenocortical tissue in the context of a germline defect and PMAH remains a mystery. PMID- 26162406 TI - GEP-NETs UPDATE: Secreting gastro-enteropancreatic neuroendocrine tumours and biomarkers. AB - Neuroendocrine tumours (NETs) are rare tumours with an annual incidence in the population in a range of 2-5 new cases per 100,000 inhabitants. NETs are widely variable in terms of anatomical location, hormone production, clinical behaviour and syndromes they can cause. This article reviews the many localizations and clinical presentations of NETs with a main focus on clinical biomarkers and their use in medical practice. PMID- 26162407 TI - L-selectin controls trafficking of chronic lymphocytic leukemia cells in lymph node high endothelial venules in vivo. AB - B-cell chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Lymph nodes (LNs) are sites of malignant proliferation and LN enlargement is associated with poor prognosis in the clinics. The LN microenvironment is believed to favor disease progression by promoting CLL cell growth and drug resistance. A better understanding of the mechanisms regulating trafficking of CLL cells to LNs is thus urgently needed. Here, we studied the first step of CLL cell migration to LNs, their interaction with high endothelial venules (HEVs), specialized blood vessels for lymphocyte extravasation in lymphoid organs. We observed that the density of HEV blood vessels was increased in CLL LNs and that CD20(+) CLL cells accumulated within HEV pockets, suggesting intense trafficking. We used intravital imaging to visualize the behavior of human CLL cells within the mouse LN microcirculation, and discovered that CLL cells bind to HEVs in vivo via a multistep adhesion cascade, which involves rolling, sticking, and crawling of the leukemic cells on the endothelium. Functional analyses revealed that the lymphocyte homing receptor L-selectin (CD62L) is the key factor controlling the binding of CLL cells to HEV walls in vivo. Interestingly, L-selectin expression was decreased on CLL cells from patients treated with idelalisib, a phosphoinositide-3-kinase delta inhibitor recently approved for CLL therapy. Interference with L-selectin-mediated trafficking in HEVs could represent a novel strategy to block dissemination of CLL cells to LNs and increase the efficacy of conventional therapy. PMID- 26162408 TI - Platelet binding sites for factor VIII in relation to fibrin and phosphatidylserine. AB - Thrombin-stimulated platelets expose very little phosphatidylserine (PS) but express binding sites for factor VIII (fVIII), casting doubt on the role of exposed PS as the determinant of binding sites. We previously reported that fVIII binding sites are increased three- to sixfold when soluble fibrin (SF) binds the alphaIIbbeta3 integrin. This study focuses on the hypothesis that platelet-bound SF is the major source of fVIII binding sites. Less than 10% of fVIII was displaced from thrombin-stimulated platelets by lactadherin, a PS-binding protein, and an fVIII mutant defective in PS-dependent binding retained platelet affinity. Therefore, PS is not the determinant of most binding sites. FVIII bound immobilized SF and paralleled platelet binding in affinity, dependence on separation from von Willebrand factor, and mediation by the C2 domain. SF also enhanced activity of fVIII in the factor Xase complex by two- to fourfold. Monoclonal antibody (mAb) ESH8, against the fVIII C2 domain, inhibited binding of fVIII to SF and platelets but not to PS-containing vesicles. Similarly, mAb ESH4 against the C2 domain, inhibited >90% of platelet-dependent fVIII activity vs 35% of vesicle-supported activity. These results imply that platelet-bound SF is a component of functional fVIII binding sites. PMID- 26162410 TI - Erratum to: Biceps Detachment Decreases Joint Damage in a Rotator Cuff Tear Rat Model. PMID- 26162409 TI - Disease evolution and outcomes in familial AML with germline CEBPA mutations. AB - In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were collected from 10 CEBPA mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course, with different mutations identified at recurrence. Deep sequencing of diagnostic and relapse paired samples confirmed that relapse-associated CEBPA mutations were absent at diagnosis, suggesting recurrence was triggered by novel, independent clones. Integrated WES and deep sequencing subsequently revealed an entirely new complement of mutations at relapse, verifying the presentation of a de novo leukemic episode. The cumulative incidence of relapse in familial AML was 56% at 10 years (n = 11), and 3 patients experienced >=3 disease episodes over a period of 17 to 20 years. Durable responses to secondary therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long term outcomes. PMID- 26162411 TI - Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture. AB - BACKGROUND: Posttraumatic osteoarthritis (OA) is a variant of OA that can develop after articular injury. Although the mechanism(s) of posttraumatic OA are uncertain, the presence and impact of postinjury proteolytic enzymes on articular cartilage remain unknown. To our knowledge, there are no studies that evaluate the presence of matrix metalloproteinases (MMPs) or aggrecan degradation after articular fracture. QUESTIONS/PURPOSES: (1) Are MMP concentrations and aggrecan degradation elevated after intraarticular fracture? (2) Are MMP concentrations and aggrecan degradation greater in high-energy injuries compared with low-energy injuries? (3) Do the concentrations of these biomarkers remain elevated at a secondary aspiration? METHODS: Between December 2011 and June 2013, we prospectively enrolled patients older than 18 years of age with acute tibial plateau fracture. Exclusion criteria included age older than 60 years, preexisting knee OA, injury greater than 24 hours before evaluation, contralateral knee injury, history of autoimmune disease, open fracture, and non English-speaking patients. During the enrollment period, we enrolled 45 of the 91 (49%) tibial plateau fractures treated at our facility. Knee synovial fluid aspirations were obtained from both the injured and uninjured knees; two patients received aspirations in the emergency department and the remaining patients received aspirations in the operating room. Twenty patients who underwent spanning external fixator followed by definitive fixation were aspirated during both surgical procedures. MMP-1, -2, -3, -7, -9, -10, -12, and -13 concentrations were quantified using multiplex assays. Aggrecan degradation was quantified using sandwich enzyme-linked immunosorbent assay. RESULTS: There were higher concentrations of MMP-1 (3.89 ng/mL [95% confidence interval {CI}, 2.37-6.37] versus 0.37 ng/mL [95% CI, 0.23-0.61], p < 0.001), MMP-3 (457.35 ng/mL [95% CI, 274.5-762.01] versus 129.17 ng/mL [95% CI, 77.01-216.66], p < 0.001), MMP-9 (6.52 ng/mL [95% CI, 3.86-11.03] versus 0.96 ng/mL [95% CI, 0.56-1.64], p < 0.001), MMP 10 (0.52 ng/mL [95% CI, 0.40-0.69] versus 0.23 ng/mL [95% CI, 0.17-0.30], p < 0.001), and MMP-12 (0.18 ng/mL [95% CI, 0.14-0.23] versus 0.10 ng/mL [95% CI, 0.0.081-0.14], p = 0.005) in injured knees compared with uninjured knees. There was not a detectable difference in MMP concentrations or aggrecan degradation between high- and low-energy injuries. MMP-1 (53.25 versus 3.89 ng/mL, p < 0.001), MMP-2 (76.04 versus 0.37 ng/mL, p < 0.001), MMP-3 (1250.62 versus 457.35 ng/mL, p = 0.002), MMP-12 (1.37 versus 0.18, p < 0.001), MMP-13 (0.98 versus 0.032 ng/mL, p < 0.001), and aggrecan degradation (0.58 versus 0.053, p < 0.001) were increased at the second procedure (mean, 9.5 days; range, 3-21 days) as compared with the initial procedure. CONCLUSIONS: Because MMPs and aggrecan degradation are elevated after articular fracture, future studies are necessary to evaluate the impact of elevated MMPs and aggrecan degradation on human articular cartilage. CLINICAL RELEVANCE: If further clinical followup can demonstrate a relationship between posttraumatic OA and elevated MMPs and aggrecan degradation, they may provide potential for therapeutic targets to prevent or delay the destruction of the joint. Additionally, these markers may offer prognostic information for patients. PMID- 26162412 TI - What Are Risk Factors for Intraoperative Humerus Fractures During Revision Reverse Shoulder Arthroplasty and Do They Influence Outcomes? AB - BACKGROUND: With the increase in shoulder arthroplasty rates, the number of perioperative complications, such as periprosthetic fractures, continues to be a rise; however, the risk factors and incidence of intraoperative complications, such as fractures, during revision reverse shoulder arthroplasty are not well established. QUESTIONS/PURPOSES: We evaluated patients receiving a reverse shoulder arthroplasty to determine (1) the frequency and characteristics of intraoperative humerus fractures, (2) the risk factors for fracture, (3) the complications associated with treatment of fractures, and (4) clinical and functional outcomes after treatment. METHODS: Using one institution's total joint registry, we performed a retrospective analysis of medical records of 224 patients (230 shoulders) who underwent revision surgery to reverse shoulder arthroplasty, from 2005 to 2012, for failed total shoulder arthroplasty. Reverse shoulder arthroplasty was used when there was a deficient rotator cuff, prior instability, or deficient glenoid bone stock. Intraoperative periprosthetic humerus fractures occurred in 36 shoulders (16%) (36 patients). The clinical outcome analysis included 29 patients with a minimum 2-year clinical followup (mean followup, 3.1 years; range, 2.0-6.3 years). The control group consisted of 188 patients (194 shoulders), and it was used for risk-factor calculation; whereas only 150 patients (154 shoulders) in the control group had a minimum 2 year followup, and thus only 150 patients (154 shoulders) made up the comparators (controls) for outcome-analysis comparisons. Risk factors were assessed using univariate analysis with odds ratios (OR), whereas implant survival and complications were assessed using the Kaplan-Meier method. RESULTS: Three displaced and 33 nondisplaced fractures occurred during revision reverse total shoulder arthroplasties. Most of the fractures (81%) occurred during component removal of cemented (n = 11) and cementless (n = 25) components. Intraoperative fractures only were treated with stabilization of the prosthetic stem in 28 patients, while adjunctive internal fixation was used in eight patients. Risk of intraoperative periprosthetic fractures was increased by factors including female sex (n =18 women; OR, 2.41; range, 1.11-5.68; p = 0.03); history of instability (n = 27; OR, 2.65; range, 1.18-5.93; p = 0.02); and prior hemiarthroplasty (n = 22; OR, 2.34; range, 1.13-4.84; p = 0.03). There were two postoperative fractures in patients who had an intraoperative fracture and both were treated nonoperatively. Overall, three (8%) revision procedures were performed in patients with intraoperative fractures, with 2- and 5-year survivorship estimates of 94% and 85%, respectively, compared with 89% and 84%, respectively for patients without an intraoperative fracture (p = 0.45). At latest followup, patients experienced good postoperative pain relief, improved shoulder abduction, and good American Shoulder and Elbow Surgeon and Simple Shoulder Test scores. CONCLUSIONS: Intraoperative humeral fractures occur in approximately 16% of shoulders undergoing revision surgery. Fractures during revision reverse TSA are not uncommon secondary to the risks of component removal in revision surgery and poor remaining bone stock. The risk seems to be greatest for female patients, patients with instability, and patients who have undergone previous hemiarthroplasties. Intraoperative humeral fractures should be approached in a systematic way to achieve anatomic reduction and stable fixation. When properly stabilized, these fractures appear not to substantially influence overall final outcome. This study provides a foundation for future investigation of methods to reduce the risk for intraoperative humeral fractures attributable to reverse revision TSA. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26162413 TI - Prevalence and Risk Factors of Spine, Shoulder, Hand, Hip, and Knee Osteoarthritis in Community-dwelling Koreans Older Than Age 65 Years. AB - BACKGROUND: Osteoarthritis (OA) is common and disabling among older patients around the world. Data exploring the prevalence and risk factors of OA are of paramount importance in establishing healthcare policies. However, few studies have evaluated these topics among Asian populations. QUESTIONS/PURPOSES: This study was conducted to determine the prevalence and risk factors of radiographic OA in the spine, shoulder, hand, hip, and knee in Koreans older than age 65 years. METHODS: A simple random sample (N = 1118) was drawn from a roster of elderly individuals older than age 65 years in Seongnam. Of the 1118 invited subjects, 696 (males = 298, females = 398) participated in this study (a response rate of 62%). The mean age of respondents was 72 +/- 5 years (range, 65-91 years). Radiographs of the lumbar spine, shoulder, hand, hip, and knee were taken and afterward evaluated for radiographic OA. The Kellgren-Lawrence grading system was used for all mentioned joints, and radiographic OA was defined as Grade 2 changes or higher. The association of sex, aging, and obesity with OA in each of the mentioned joints was determined with the help of multivariate logistic regression. RESULTS: The highest prevalence of radiographic OA was seen in the spine (number of subjects with OA/number of whole population = 462 of 696 [66%]) followed by the hand (415 of 692 [60%]), knee (265 of 696 [38%]), shoulder (36 of 696 [5%]), and hip (15 of 686 [2%]). Female sex was associated with knee OA (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.9-8.4; p < 0.001) and hand OA (OR, 2.3; 95% CI, 1.6-3.1; p < 0.001), and male sex was associated with spine OA (OR, 0.7; 95% CI, 0.5-1.0; p = 0.025). Aging was associated with radiographic OA in the spine, knee, and hand (OR per 5-year increments, 1.3 [95% CI, 1.1-1.6; p = 0.001], 1.6 [95% CI, 1.4-1.9; p < 0.001], and 1.4 [95% CI, 1.2-1.7; p < 0.001]), respectively) but not associated with OA in the hip and shoulder. Obesity was associated with knee OA (OR, 3.4; 95% CI, 2.4-5.0; p < 0.001) and spine OA (OR, 1.5; 95% CI, 1.1-2.2; p = 0.014) but not with OA in other joints. CONCLUSIONS: OA of the spine, hand, and knee is likely to become a major public health problem rather than shoulder and hip OA in Korea. Associations of demographic factors with radiographic OA differed among each joint, and that would be valuable information to assess the role and influence of risk factors of OA in various joints. LEVEL OF EVIDENCE: Level III, prognostic study. PMID- 26162414 TI - Delayed Auditory Brainstem Responses in Prelingually Deaf and Late-Implanted Cochlear Implant Users. AB - Neurophysiological studies in animals and humans suggest that severe hearing loss during early development impairs the maturation of the auditory brainstem. To date, studies in humans have mainly focused on the neural activation of the auditory brainstem in children treated with a cochlear implant (CI), but little is known about the pattern of activation in adult CI users with early onset of deafness (prelingual, before the age of 2 years). In this study, we compare auditory brainstem activation in prelingually deaf and late-implanted adult CI users to that in postlingually deaf CI users. Electrically evoked auditory brainstem responses (eABRs) were recorded by monopolar stimulation, separately using a middle and an apical electrode of the CI. Comparison of the eABR latencies revealed that wave V was significantly delayed in the prelingually deaf CI users on both electrode locations. Accordingly, when the apical electrode was stimulated, the III-V interwave interval was significantly longer in the prelingually deaf group. These findings suggest a slower neural conduction in the auditory brainstem, probably caused by impairment of maturation during the long duration of severe hearing loss in infancy. Shorter wave V latencies, reflecting a more mature brainstem, appeared to be a predictor for better speech perception. PMID- 26162415 TI - Specificity of the Human Frequency Following Response for Carrier and Modulation Frequency Assessed Using Adaptation. AB - The frequency following response (FFR) is a scalp-recorded measure of phase locked brainstem activity to stimulus-related periodicities. Three experiments investigated the specificity of the FFR for carrier and modulation frequency using adaptation. FFR waveforms evoked by alternating-polarity stimuli were averaged for each polarity and added, to enhance envelope, or subtracted, to enhance temporal fine structure information. The first experiment investigated peristimulus adaptation of the FFR for pure and complex tones as a function of stimulus frequency and fundamental frequency (F0). It showed more adaptation of the FFR in response to sounds with higher frequencies or F0s than to sounds with lower frequency or F0s. The second experiment investigated tuning to modulation rate in the FFR. The FFR to a complex tone with a modulation rate of 213 Hz was not reduced more by an adaptor that had the same modulation rate than by an adaptor with a different modulation rate (90 or 504 Hz), thus providing no evidence that the FFR originates mainly from neurons that respond selectively to the modulation rate of the stimulus. The third experiment investigated tuning to audio frequency in the FFR using pure tones. An adaptor that had the same frequency as the target (213 or 504 Hz) did not generally reduce the FFR to the target more than an adaptor that differed in frequency (by 1.24 octaves). Thus, there was no evidence that the FFR originated mainly from neurons tuned to the frequency of the target. Instead, the results are consistent with the suggestion that the FFR for low-frequency pure tones at medium to high levels mainly originates from neurons tuned to higher frequencies. Implications for the use and interpretation of the FFR are discussed. PMID- 26162416 TI - Nonlinear Vibration Response Measured at Umbo and Stapes in the Rabbit Middle ear. AB - Using laser vibrometry and a stimulation and signal analysis method based on multisines, we have measured the response and the nonlinearities in the vibration of the rabbit middle ear at the level of the umbo and the stapes. With our method, we were able to detect and quantify nonlinearities starting at sound pressure levels of 93-dB SPL. The current results show that no significant additional nonlinearity is generated as the vibration signal is passed through the middle ear chain. Nonlinearities are most prominent in the lower frequencies (125 Hz to 1 kHz), where their level is about 40 dB below the vibration response. The level of nonlinearities rises with a factor of nearly 2 as a function of sound pressure level, indicating that they may become important at very high sound pressure levels such as those used in high-power hearing aids. PMID- 26162417 TI - Repeated Moderate Noise Exposure in the Rat--an Early Adulthood Noise Exposure Model. AB - In this study, we investigated the effects of varying intensity levels of repeated moderate noise exposures on hearing. The aim was to define an appropriate intensity level that could be repeated several times without giving rise to a permanent hearing loss, and thus establish a model for early adulthood moderate noise exposure in rats. Female Sprague-Dawley rats were exposed to broadband noise for 90 min, with a 50 % duty cycle at levels of 101, 104, 107, or 110 dB sound pressure level (SPL), and compared to a control group of non-exposed animals. Exposure was repeated every 6 weeks for a maximum of six repetitions or until a permanent hearing loss was observed. Hearing was assessed by the auditory brainstem response (ABR). Rats exposed to the higher intensities of 107 and 110 dB SPL showed permanent threshold shifts following the first exposure, while rats exposed to 101 and 104 dB SPL could be exposed at least six times without a sustained change in hearing thresholds. ABR amplitudes decreased over time for all groups, including the non-exposed control group, while the latencies were unaffected. A possible change in noise susceptibility following the repeated moderate noise exposures was tested by subjecting the animals to high-intensity noise exposure of 110 dB for 4 h. Rats previously exposed repeatedly to 104 dB SPL were slightly more resistant to high-intensity noise exposure than non exposed rats or rats exposed to 101 dB SPL. Repeated moderate exposure to 104 dB SPL broadband noise is a viable model for early adulthood noise exposure in rats and may be useful for the study of noise exposure on age-related hearing loss. PMID- 26162418 TI - Understanding How Mindful Parenting May Be Linked to Mother-Adolescent Communication. AB - Researchers have sought to understand the processes that may promote effective parent-adolescent communication because of the strong links to adolescent adjustment. Mindfulness, a relatively new construct in Western psychology that derives from ancient Eastern traditions, has been shown to facilitate communication and to be beneficial when applied in the parenting context. In this article, we tested if and how mindful parenting was linked to routine adolescent disclosure and parental solicitation within a longitudinal sample of rural and suburban, early adolescents and their mothers (n = 432; mean adolescent age = 12.14, 46 % male, 72 % Caucasian). We found that three factors-negative parental reactions to disclosure, adolescent feelings of parental over-control, and the affective quality of the parent-adolescent relationship-mediated the association between mindful parenting and adolescent disclosure and parental solicitation. Results suggest that mindful parenting may improve mother-adolescent communication by reducing parental negative reactions to information, adolescent perceptions of over-control, and by improving the affective quality of the parent adolescent relationship. The discussion highlights intervention implications and future directions for research. PMID- 26162419 TI - Implications of the IQ-CSRC Prospective Study: Time to Revise ICH E14. AB - Exposure-response (ER) analysis has evolved as an important tool to evaluate the effect of a drug on cardiac repolarization, as reflected in the QTc interval. It has been suggested that careful electrocardiogram (ECG) evaluation in 'first-in human' studies using ER analysis could replace or serve as an alternative to the E14 'thorough QT' study. This commentary shares and discusses the results of a recently conducted study with the objective to evaluate this approach. Six drugs with a well-characterized QT effect, five of which are known QT prolongers, were evaluated in a study design similar to a conventional single-ascending-dose study. Each drug was given to nine healthy subjects (six for placebo) in two dose levels, which for the positive drugs (ondansetron, quinine, dolasetron, moxifloxacin, and dofetilide) were chosen with the intent to cause 10-12 ms and 15-20 ms QTc prolongation. Replicate 12-lead ECGs were extracted from continuous recordings pre-dose and serially after dosing and paired with drug concentration determinations. The ER criteria for the identification of a QT effect, a statistically significant positive ER slope and an effect above 10 ms, were met with all five positive drugs, and an effect exceeding 10 ms could be excluded at the supratherapeutic dose of the negative drug, levocetirizine. The study results thereby provided evidence to support that careful QT assessment in early phase clinical studies can be used as an alternative to the thorough QT study. Clinical and regulatory implications, as well as limitations of this approach, are discussed in the commentary. PMID- 26162420 TI - Safety and feasibility of endoscopic biliary radiofrequency ablation treatment of extrahepatic cholangiocarcinoma. AB - BACKGROUND: Biliary bipolar radiofrequency ablation (RFA) is a new treatment for extrahepatic cholangiocarcinoma (CCA) currently under evaluation. The purpose of this study was to evaluate the safety, particularly biliary fistula occurrence, and the feasibility of biliary RFA in a homogeneous group of patients treated using the same RFA protocol. METHODS: Twelve patients with inoperable or unresectable CCA were included in a bicentric case series study. After removal of biliary plastic stents, a radiofrequency treatment with a new bipolar probe (HabibTM EndoHBP) was applied. The energy was delivered by a RFA generator (VIO 200 D), supplying electrical energy at 350 kHz and 10 W for 90 s. At the end of the procedure, one or more biliary stents were left in place. Adverse events were assessed per-procedure and during follow-up visits. RESULTS: CCA was confirmed in all patients by histology (66%), locoregional evolution or metastatic evolution. The types of CCA were Bismuth I stage (N = 4), Bismuth II stage (N = 3), Bismuth III stage (N = 2) and Bismuth IV stage (N = 3). No serious adverse events occurred within 30 days following endoscopic treatment: One patient had a sepsis due to bacterial translocation on day 1 and another had an acute cholangitis on day 12 due to early stent migration. No immediate or delayed biliary fistula was reported. The ergonomics of the probe made treatment easy in 100 % of cases. Mean survival was 12.3 months. CONCLUSION: Endoscopic radiofrequency treatment of inoperable CCA appears without major risks and is feasible. No major adverse events or biliary fistula were identified. PMID- 26162421 TI - Gastrointestinal symptoms, weight loss and patient satisfaction 5 years after gastric bypass: a study of three techniques for the gastrojejunal anastomosis. AB - BACKGROUND: The optimal operative technique in gastric bypass (RYGB) is still under debate. We have studied patient-reported gastrointestinal symptoms and weight loss 5 years after RYGB performed with three different stapling techniques for the gastrojejunal anastomosis (GJ). METHODS: Out of 593 patients operated with RYGB, 489 patients [80.2% women, body mass index (BMI) 44.9 (33-68) kg/m(2)] answered our 5-year follow-up questionnaire concerning gastrointestinal symptoms (vomiting, reflux, dumping, abdominal pain or diarrhea), weight loss, need for postoperative endoscopic interventions and overall satisfaction with the procedure. We compared the results for three different GJ techniques: linear stapler (LS, n = 103), 21-mm circular stapler (C21, n = 88) and 25-mm circular stapler (C25, n = 298). RESULTS: Dumping was the most commonly reported symptom (14.1% of all patients on a weekly to daily basis), however, less frequently reported in the C25 group (p < 0.05). Vomiting, prevalent in 2.9% of all patients, was more frequently reported in the C21 group (p < 0.01). No group consistently showed greater weight loss compared to the other two groups. A higher incidence of endoscopic dilatations due to strictures was reported in the C21 group (12.5% compared to 4.5% of all patients, p < 0.05). Overall patient satisfaction was high (88%). CONCLUSION: Our data suggest that the technique for the construction of the GJ in RYGB affects gastrointestinal symptoms 5 years postoperatively. The difference is moderate but indicates that a narrow GJ results in increased frequency of vomiting and need for endoscopic interventions without improving the weight result. PMID- 26162422 TI - Single-port versus conventional laparoscopic total extra-peritoneal inguinal hernia repair: a prospective, randomized, controlled clinical trial. AB - BACKGROUND: The advantage of single-port total extra-peritoneal (TEP) inguinal hernia repair over the conventional technique is still debatable. Our objective was to compare the outcomes of TEP inguinal hernia repair using either a single port or conventional surgical technique, in two blind randomized groups of patients. METHODS: In this prospective, randomized, double-blind, controlled clinical trial, 100 patients undergoing surgery for unilateral inguinal hernia were randomized into two groups: One group underwent conventional laparoscopic TEP inguinal hernia repair, while the other was selected for single-port TEP repair. Primary endpoint is postoperative pain (VAS), while secondary endpoints are recurrence, chronic pain and complications. RESULTS: From 100 patients, 49 underwent single-port hernia TEP repair, 50 had conventional three-port TEP hernia repair, and one patient declined to participate after randomization. The two groups were comparable in terms of patient demographics and operative findings. Mean operative time was 49.1(+/-13.8) min in the conventional group and 54.1(+/-14.4) min in the single-port group (p = 0.08). Mean hospital stay was 19.7(+/-5.8) h in the conventional group and 20.5(+/-6.4) h in the single-port group (p = 0.489). No major complications and no recurrence reported at 11-month follow-up. No statistically significant difference noted in postoperative pain between the two groups at regular intervals. CONCLUSIONS: The outcomes after laparoscopic TEP inguinal hernia repair with a single-port device are similar but not superior to the conventional technique. PMID- 26162423 TI - Laparoscopic partial nephrectomy without intracorporeal suturing. AB - BACKGROUND: Partial nephrectomy has gained wider acceptance as a surgical technique in treating small renal tumors. Laparoscopic partial nephrectomy (LPN) still remains a technically demanding surgery to this day. We present our technique of laparoscopic partial nephrectomy, one that is performed without intracorporeal suturing. METHODS: We performed LPN on 31 patients with localized renal parenchymal tumor (stage T1). The procedures were done from September 2009 to March 2015 at the Kaohsiung Medical University Hospital and the Kaohsiung Municipal Ta-Tung Hospital. Our technique involves the covering of renal defect layer by layer with FloSeal, Tisseel and a fat pad after monopolar coagulation. RESULTS: Thirty-one patients were included in this study. Mean patient age was 53 years old (range 39-70). Mean tumor size was 2.9 cm (range 1.8-6.3). Mean RENAL nephrometry score was 5.3 (range 4-7). The average operation time was 188 min (range 120-290), and the average warm ischemic time was 19.0 min (range 9-26). Mean estimated blood loss was 171 ml (range 10-650), with no postoperative bleeding among the total 31 patients. No recurrent tumors were identified at a mean follow-up of 29 months postoperatively. The mean change in eGFR was 6.5 (ml/min/m2). CONCLUSION: Laparoscopic partial nephrectomy is a feasible surgical method for most patients with stage 1 tumor. Our technique has shown to reduce warm ischemic time significantly and provide patients with excellent functional outcomes without affecting oncological results. With this technique, surgeons can perform LPN with more efficiency and with fewer complications. PMID- 26162424 TI - Chronic metabolic acidosis reduces urinary oxalate excretion and promotes intestinal oxalate secretion in the rat. AB - Urinary oxalate excretion is reduced in rats during a chronic metabolic acidosis, but how this is achieved is not clear. In this report, we re-examine our prior work on the effects of a metabolic acidosis on urinary oxalate handling [Green et al., Am J Physiol Ren Physiol 289(3):F536-F543, 2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport. Sprague-Dawley rats were provided with 0.28 M ammonium chloride in their drinking water for either 4 or 14 days followed by 24 h urine collections, blood-gas and serum ion analysis, and measurements of (14)C-oxalate fluxes across isolated segments of the distal colon. Urinary oxalate excretion was significantly reduced by 75% after just 4 days compared to control rats, and this was similarly sustained at 14 days. Oxalate:creatinine clearance ratios indicated enhanced net re-absorption of oxalate by the kidney during a metabolic acidosis, but this was not associated with any substantive changes to serum oxalate levels. In the distal colon, oxalate transport was dramatically altered from net absorption in controls (6.20 +/- 0.63 pmol cm(-2) h(-1)), to net secretion in rats with a metabolic acidosis (-5.19 +/- 1.18 and -2.07 +/- 1.05 pmol cm(-2) h( 1) at 4 and 14 days, respectively). Although we cannot rule out modifications to bi-directional oxalate movements along the proximal tubule, these findings support a gut-kidney axis in the management of oxalate homeostasis, where this shift in renal handling during a metabolic acidosis is associated with compensatory adaptations by the intestine. PMID- 26162425 TI - Products of biotransformation of polycyclic aromatic hydrocarbons in fishes of the Athabasca/Slave river system, Canada. AB - Concentrations of products of biotransformation of polycyclic aromatic hydrocarbons (PBPAH) were measured in bile of five fishes of nutritional, cultural and ecological relevance from the Athabasca/Slave river system. Samples were collected in Alberta and the Northwest Territories, Canada, during three seasons. As a measure of concentrations of PBPAHs to which fishes are exposed and to gain information on the nature and extent of potential exposures of people or piscivorous wildlife, concentrations of biotransformation products of two- and three-ringed, four-ringed and five-ringed PAHs were measured using synchronous fluorescence spectroscopy. Spatial and seasonal differences were observed with greater concentrations of PBPAHs in samples of bile of fish collected from Fort McKay as well as greater concentrations of PBPAHs in bile of fish collected during summer compared to those collected in other seasons. Overall, PBPAHs were greater in fishes of lower trophic levels and fishes more closely associated with sediments. In particular, goldeye (Hiodon alosoides), consistently contained greater concentrations of all the PBPAHs studied. PMID- 26162426 TI - Molecular Characterization and In Silico Analysis of Defensin From Tor putitora (Hamilton). AB - Antimicrobial peptides (AMPs) are vital constituents of innate immune system. In fish, one of the most important AMP is beta-defensin that has a potential to activate the adaptive immune system. beta-defensin is a cysteine-arginine-rich cationic AMP with broad spectrum activity against microbes. In this study, we identified cloned and characterized beta-defensin 1 from Tor putitora, a cold water fish species also known as mahseer. An open reading frame of beta-defensin 1 was amplified, cloned and sequenced which encodes a peptide of 67 amino acid residues. The pro-peptide includes a signal peptide comprising 24 amino acids as predicted by Signal P along with a mature peptide of 43 amino acid residues. Tor putitora beta-defensin 1 (TP-betadf1) has a molecular weight of 4.6 kDa with a pI of 8.35. Six cysteine residues are present in the mature peptide which is a characteristic feature of defensins. All six cysteine residues are involved in the formation of three intra-molecular disulfide bonds. Three-dimensional modeling of mature peptide of TP-betadf1 was carried out using Modeller 9.10, and validated TP-betadf1 model revealed three beta-sheets. The cysteine residues form three disulfide bonds in the pattern of Cys(1)-Cys(5), Cys(2)-Cys(4), Cys(3) Cys(6) stabilizing the beta-sheet. Structural analysis revealed three beta strands and an alpha-helix at the N terminus. Phylogenetic analysis revealed that the beta-defensin 1 of Tor putitora was close to Megalobrama amblycephala which possibly suggests that TP-betadf1 peptide sequence is quite similar to beta defensin peptide sequences of carps and minnows. PMID- 26162427 TI - Facing the Future: Effects of Short-Term Climate Extremes on Isoprene-Emitting and Nonemitting Poplar. AB - Isoprene emissions from poplar (Populus spp.) plantations can influence atmospheric chemistry and regional climate. These emissions respond strongly to temperature, [CO2], and drought, but the superimposed effect of these three climate change factors are, for the most part, unknown. Performing predicted climate change scenario simulations (periodic and chronic heat and drought spells [HDSs] applied under elevated [CO2]), we analyzed volatile organic compound emissions, photosynthetic performance, leaf growth, and overall carbon (C) gain of poplar genotypes emitting (IE) and nonemitting (NE) isoprene. We aimed (1) to evaluate the proposed beneficial effect of isoprene emission on plant stress mitigation and recovery capacity and (2) to estimate the cumulative net C gain under the projected future climate. During HDSs, the chloroplastidic electron transport rate of NE plants became impaired, while IE plants maintained high values similar to unstressed controls. During recovery from HDS episodes, IE plants reached higher daily net CO2 assimilation rates compared with NE genotypes. Irrespective of the genotype, plants undergoing chronic HDSs showed the lowest cumulative C gain. Under control conditions simulating ambient [CO2], the C gain was lower in the IE plants than in the NE plants. In summary, the data on the overall C gain and plant growth suggest that the beneficial function of isoprene emission in poplar might be of minor importance to mitigate predicted short-term climate extremes under elevated [CO2]. Moreover, we demonstrate that an analysis of the canopy-scale dynamics of isoprene emission and photosynthetic performance under multiple stresses is essential to understand the overall performance under proposed future conditions. PMID- 26162428 TI - CATION EXCHANGER1 Cosegregates with Cadmium Tolerance in the Metal Hyperaccumulator Arabidopsis halleri and Plays a Role in Limiting Oxidative Stress in Arabidopsis Spp. AB - Arabidopsis halleri is a model species for the study of plant adaptation to extreme metallic conditions. In this species, cadmium (Cd) tolerance seems to be constitutive, and the mechanisms underlying the trait are still poorly understood. A previous quantitative trait loci (QTL) analysis performed on A. halleri * Arabidopsis lyrata backcross population1 identified the metal-pump gene Heavy Metal ATPase4 as the major genetic determinant for Cd tolerance. However, although necessary, Heavy Metal ATPase4 alone is not sufficient for determining this trait. After fine mapping, a gene encoding a calcium(2+)/hydrogen(+) antiporter, cation/hydrogen(+) exchanger1 (CAX1), was identified as a candidate gene for the second QTL of Cd tolerance in A. halleri. Backcross population1 individuals displaying the A. halleri allele for the CAX1 locus exhibited significantly higher CAX1 expression levels compared with the ones with the A. lyrata allele, and a positive correlation between CAX1 expression and Cd tolerance was observed. Here, we show that this QTL is conditional and that it is only detectable at low external Ca concentration. CAX1 expression in both roots and shoots was higher in A. halleri than in the close Cd-sensitive relative species A. lyrata and Arabidopsis thaliana. Moreover, CAX1 loss of function in A. thaliana led to higher Cd sensitivity at low concentration of Ca, higher sensitivity to methylviologen, and stronger accumulation of reactive oxygen species after Cd treatment. Overall, this study identifies a unique genetic determinant of Cd tolerance in the metal hyperaccumulator A. halleri and offers a new twist for the function of CAX1 in plants. PMID- 26162430 TI - Sensitive Detection of Phosphorus Deficiency in Plants Using Chlorophyll a Fluorescence. AB - Phosphorus (P) is a finite natural resource and an essential plant macronutrient with major impact on crop productivity and global food security. Here, we demonstrate that time-resolved chlorophyll a fluorescence is a unique tool to monitor bioactive P in plants and can be used to detect latent P deficiency. When plants suffer from P deficiency, the shape of the time-dependent fluorescence transients is altered distinctively, as the so-called I step gradually straightens and eventually disappears. This effect is shown to be fully reversible, as P resupply leads to a rapid restoration of the I step. The fading I step suggests that the electron transport at photosystem I (PSI) is affected in P-deficient plants. This is corroborated by the observation that differences at the I step in chlorophyll a fluorescence transients from healthy and P-deficient plants can be completely eliminated through prior reduction of PSI by far-red illumination. Moreover, it is observed that the barley (Hordeum vulgare) mutant Viridis-zb(63), which is devoid of PSI activity, similarly does not display the I step. Among the essential plant nutrients, the effect of P deficiency is shown to be specific and sufficiently sensitive to enable rapid in situ determination of latent P deficiency across different plant species, thereby providing a unique tool for timely remediation of P deficiency in agriculture. PMID- 26162429 TI - RNA Interference Knockdown of BRASSINOSTEROID INSENSITIVE1 in Maize Reveals Novel Functions for Brassinosteroid Signaling in Controlling Plant Architecture. AB - Brassinosteroids (BRs) are plant hormones involved in various growth and developmental processes. The BR signaling system is well established in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) but poorly understood in maize (Zea mays). BRASSINOSTEROID INSENSITIVE1 (BRI1) is a BR receptor, and database searches and additional genomic sequencing identified five maize homologs including duplicate copies of BRI1 itself. RNA interference (RNAi) using the extracellular coding region of a maize zmbri1 complementary DNA knocked down the expression of all five homologs. Decreased response to exogenously applied brassinolide and altered BR marker gene expression demonstrate that zmbri1-RNAi transgenic lines have compromised BR signaling. zmbri1-RNAi plants showed dwarf stature due to shortened internodes, with upper internodes most strongly affected. Leaves of zmbri1-RNAi plants are dark green, upright, and twisted, with decreased auricle formation. Kinematic analysis showed that decreased cell division and cell elongation both contributed to the shortened leaves. A BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1-yellow fluorescent protein (BES1-YFP) transgenic line was developed that showed BR inducible BES1-YFP accumulation in the nucleus, which was decreased in zmbri1 RNAi. Expression of the BES1-YFP reporter was strong in the auricle region of developing leaves, suggesting that localized BR signaling is involved in promoting auricle development, consistent with the zmbri1-RNAi phenotype. The blade-sheath boundary disruption, shorter ligule, and disrupted auricle morphology of RNAi lines resemble KNOTTED1-LIKE HOMEOBOX (KNOX) mutants, consistent with a mechanistic connection between KNOX genes and BR signaling. PMID- 26162431 TI - Community Influences on Married Women's Safer Sex Negotiation Attitudes in Bangladesh: A Multilevel Analysis. AB - The influence of disadvantaged or deprived community on individuals' health risk behaviors is increasingly being documented in a growing body of literature. However, little is known about the effects of community characteristics on women's sexual attitudes and behaviors. To examine community effects on married women's safer sex negotiation attitudes, we analyzed cross-sectional data from the 2011 Bangladesh Demographic and Health Surveys on a sample of 15,134 married women in 600 communities. We estimated two multilevel logistic regression models. Model 1, which included only individual-level variables, showed that women's autonomy/empowerment, age, and HIV knowledge had significant associations with their safer sex negotiation attitudes. We did not find any socioeconomic status gradient in safer sex negotiation attitudes at the individual level. Adding community-level variables in Model 2 significantly improved the fit of the model. Strikingly, we found that higher community-level poverty was associated with greater positive safer sex negotiation attitudes. Prevailing gender norms and overall women's empowerment in the community also had significant effects. While research on community influences calls for focusing on disadvantaged communities, our research highlights the importance of not underestimating the challenges that married women in economically privileged communities may face in negotiating safer sex. To have sufficient and equitable impact on married women's sexual and reproductive health, sexual and reproductive health promotion policies and programs need to be directed to women in wealthier communities as well. PMID- 26162432 TI - Cost Considerations in the Evaluation and Treatment of Colorectal Cancer. AB - OPINION STATEMENT: As the cost of cancer care in the United States continues to climb at an alarming rate, it is critically important for the oncology community to begin embracing interventions that provide value to patients and society. This is particularly important in the field of colorectal cancer, where many new high priced drugs have emerged over the past several years. While adjuvant chemotherapy (FOLFOX and capecitabine) has been shown to fall within accepted thresholds for cost-effectiveness, many interventions in the metastatic setting have not. Bevacizumab in the first- and second-line settings as well as EGFR inhibitors across all lines of therapy have been associated with unfavorable cost effectiveness ratios in several studies conducted in the United States and other countries. A key strategy in improving the cost-effectiveness of CRC treatment in the advanced setting will therefore be to identify predictive biomarkers (e.g., RAS mutation) for therapeutic response to existing drugs as well as drugs in development so that high-priced therapies can be administered to patients most likely to benefit and avoided in those who would not. PMID- 26162433 TI - On the role of gut bacteria and infant diet in the development of autoimmunity for type 1 diabetes. PMID- 26162434 TI - Synthesis and biological activity evaluation of novel amino acid derivatives as potential elicitors against Tomato yellow leaf curl virus. AB - Disease caused by Tomato yellow leaf curl virus (TYLCV) brings serious production losses of cultivated tomato worldwide. In our previous study, two novel amino acid derivatives exerted satisfactory antiviral activities against TYLCV. In this study, the variation of TYLCV, the transcriptional expression level of Ty-1 and the enzyme activities of POD and PPO in tomato were monitored after treatment with two amino acid derivatives to illustrate the antiviral mechanism. The results showed the symptom severity caused by TYLCV was reduced significantly by two compounds and was associated with the inhibition of viral DNA level at the early stage. Among three levels of concentration, the highest inhibition rate of CNBF-His was 40.66% at 1000 mg/L, for CNBF-Asn, the highest inhibition rate was 36.26% at 2000 mg/L 30 days post-inoculation. Two compounds could also enhance the activities of PPO and POD and the transcriptional expression level of Ty-1 which correlates with plant resistance in tomato. In the field test, two compounds increased the yields of tomato and the maximum increase of yield was 37.66%. This is the first report of novel amino acid derivatives inducing resistance in tomato plant against TYLCV. It is suggested that amino acid derivatives have the potential to be an effective approach against TYLCV in tomato plant. PMID- 26162435 TI - D-Amino acids incorporation in the frog skin-derived peptide esculentin-1a(1 21)NH2 is beneficial for its multiple functions. AB - Naturally occurring antimicrobial peptides (AMPs) represent promising future antibiotics. We have previously isolated esculentin-1a(1-21)NH2, a short peptide derived from the frog skin AMP esculentin-1a, with a potent anti-Pseudomonal activity. Here, we investigated additional functions of the peptide and properties responsible for these activities. For that purpose, we synthesized the peptide, as well as its structurally altered analog containing two D-amino acids. The peptides were then biophysically and biologically investigated for their cytotoxicity and immunomodulating activities. The data revealed that compared to the wild-type, the diastereomer: (1) is significantly less toxic towards mammalian cells, in agreement with its lower alpha-helical structure, as determined by circular dichroism spectroscopy; (2) is more effective against the biofilm form of Pseudomonas aeruginosa (responsible for lung infections in cystic fibrosis sufferers), while maintaining a high activity against the free-living form of this important pathogen; (3) is more stable in serum; (4) has a higher activity in promoting migration of lung epithelial cells, and presumably in healing damaged lung tissue, and (5) disaggregates and detoxifies the bacterial lipopolysaccharide (LPS), albeit less than the wild-type. Light scattering studies revealed a correlation between anti-LPS activity and the ability to disaggregate the LPS. Besides shedding light on the multifunction properties of esculentin-1a(1-21)NH2, the D-amino acid containing isomer may serve as an attractive template for the development of new anti-Pseudomonal compounds with additional beneficial properties. Furthermore, together with other studies, incorporation of D-amino acids may serve as a general approach to optimize the future design of new AMPs. PMID- 26162436 TI - Composition of distinct sub-proteomes in Myxococcus xanthus: metabolic cost and amino acid availability. AB - Subsets of proteins involved in distinct functional processes are subject to different selective pressures. We investigated whether there is an amino acid composition bias (AACB) inherent in discrete subsets of proteins, and whether we could identify changing patterns of AACB during the life cycle of the social bacterium Myxococcus xanthus. We quantitatively characterised the cellular, soluble secreted, and outer membrane vesicle (OMV) sub-proteomes of M. xanthus, identifying 315 proteins. The AACB of the cellular proteome differed only slightly from that deduced from the genome, suggesting that genome-inferred proteomes can accurately reflect the AACB of their host. Inferred AA deficiencies arising from prey consumption were exacerbated by the requirements of the 68%GC genome, whose character thus seems to be selected for directly rather than via the proteome. In our analysis, distinct subsets of the proteome (whether segregated spatially or temporally) exhibited distinct AACB, presumably tailored according to the needs of the organism's lifestyle and nutrient availability. Secreted AAs tend to be of lower cost than those retained in the cell, except for the early developmental A-signal, which is a particularly costly sub-proteome. We propose a model of AA reallocation during the M. xanthus life cycle, involving ribophagy during early starvation and sequestration of limiting AAs within cells during development. PMID- 26162437 TI - Epigenetics and systemic sclerosis. AB - Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vascular injury, activation of the immune system, and diffuse tissue fibrosis. The precise etiology of SSc is undetermined, but there is evidence suggestive of a connection between environmental factors and SSc pathogenesis. In general, harmful environmental factors are sensed by the epigenetic regulatory mechanisms that alter host gene expression leading to the emergence of disease-specific phenotype. There are three epigenetic mechanisms involved in gene regulation: DNA methylation, histone modifications, and microRNAs. Although there is evidence that SSc phenotype could be, to a some degree, determined by genetic variants, it is clear now that non-genetic factors outweigh the genetic risk in SSc. Accordingly, the environment can trigger epigenetic regulation that in turn establishes a molecular framework linking environmental exposures to genetics, leading to the disease process, possibly in a genetically predisposed host. Although we have just begun to appreciate the potential role of epigenetics in SSc, many important and promising clues have been observed. In this review, we will summarize the work that has been done in the field of epigenetic regulation in SSc, and we will discuss possible factors and mechanisms that may lead to epigenetic dysregulation in SSc. PMID- 26162438 TI - Design of a toxicity biosensor based on Aliivibrio fischeri entrapped in a disposable card. AB - The degradation of the marine environment is a subject of concern for the European authorities primarily because of its contamination by hydrocarbons. The traditional methods (ISO 11348 standard) of general toxicity assessment are unsuitable in a context of in situ monitoring, such as seaports or bathing zones. Consequently, to address this issue, bacterial biosensors appear to be pertinent tools. This article presents the design of an innovative bioluminescent biosensor dedicated to in situ toxicity monitoring. This biosensor is based on the entrapment of the wild marine bioluminescent bacterial strain Aliivibrio fischeri ATCC(r) 49387TM in an agarose matrix within a disposable card. A pre-study was needed to select the most biological parameters. In particular, the regenerating medium's composition and the hydrogel concentration needed for the bacterial entrapment (mechanical resistance) were optimized. Based on these data, the ability of the bacterial reporter to assess the sample toxicity was demonstrated using naphthalene as a chemical model. The biosensor's results show a lower sensitivity to naphthalene (EC50 = 95 mg/L) compared with the results obtained using the reference method (EC50 = 43 mg/L). With this architecture, the biosensor is an interesting compromise among low maintenance, ease of use, appropriate sensitivity, relatively low cost and the ability to control online toxicity. PMID- 26162439 TI - Polychlorinated biphenyl (PCB) anaerobic degradation in marine sediments: microcosm study and role of autochthonous microbial communities. AB - Polychlorobiphenyl (PCB) biodegradation was followed for 1 year in microcosms containing marine sediments collected from Mar Piccolo (Taranto, Italy) chronically contaminated by this class of hazardous compounds. The microcosms were performed under strictly anaerobic conditions with or without the addition of Dehalococcoides mccartyi, the main microorganism known to degrade PCBs through the anaerobic reductive dechlorination process. Thirty PCB congeners were monitored during the experiments revealing that the biodegradation occurred in all microcosms with a decrease in hepta-, hexa-, and penta-chlorobiphenyls (CBs) and a parallel increase in low chlorinated PCBs (tri-CBs and tetra-CBs). The concentrations of the most representative congeners detected in the original sediment, such as 245-245-CB and 2345-245-CB, and of the mixture 2356-34-CB+234 245-CB, decreased by 32.5, 23.8, and 46.7 %, respectively, after only 70 days of anaerobic incubation without any bioaugmentation treatment. Additionally, the structure and population dynamics of the microbial key players involved in the biodegradative process and of the entire mixed microbial community were accurately defined by Catalyzed Reporter Deposition Fluorescence In Situ Hybridization (CARD-FISH) in both the original sediment and during the operation of the microcosm. The reductive dehalogenase genes of D. mccartyi, specifically involved in PCB dechlorination, were also quantified using real-time PCR (qPCR). Our results demonstrated that the autochthonous microbial community living in the marine sediment, including D. mccartyi (6.32E+06 16S rRNA gene copy numbers g(-1) sediment), was able to efficiently sustain the biodegradation of PCBs when controlled anaerobic conditions were imposed. PMID- 26162440 TI - A multiscale modelling methodology applicable for regulatory purposes taking into account effects of complex terrain and buildings on pollutant dispersion: a case study for an inner Alpine basin. AB - Dispersion modelling in complex terrain always has been challenging for modellers. Although a large number of publications are dedicated to that field, candidate methods and models for usage in regulatory applications are scarce. This is all the more true when the combined effect of topography and obstacles on pollutant dispersion has to be taken into account. In Austria, largely situated in Alpine regions, such complex situations are quite frequent. This work deals with an approach, which is in principle capable of considering both buildings and topography in simulations by combining state-of-the-art wind field models at the micro- (<1 km) and mesoscale gamma (2-20 km) with a Lagrangian particle model. In order to make such complex numerical models applicable for regulatory purposes, meteorological input data for the models need to be readily derived from routine observations. Here, use was made of the traditional way to bin meteorological data based on wind direction, speed, and stability class, formerly mainly used in conjunction with Gaussian-type models. It is demonstrated that this approach leads to reasonable agreements (fractional bias < 0.1) between observed and modelled annual average concentrations in an Alpine basin with frequent low-wind speed conditions, temperature inversions, and quite complex flow patterns, while keeping the simulation times within the frame of possibility with regard to applications in licencing procedures. However, due to the simplifications in the derivation of meteorological input data as well as several ad hoc assumptions regarding the boundary conditions of the mesoscale wind field model, the methodology is not suited for computing detailed time and space variations of pollutant concentrations. PMID- 26162441 TI - Environmental microbiology reveals the Earth secret life. PMID- 26162442 TI - Use of multi-objective dredging for remediation of contaminated sediments: a case study of a typical heavily polluted confluence area in China. AB - Sediments in confluence areas are typically contaminated by various pollutants that have been transported there by inflowing rivers. In this study, we evaluated the pollution status of a confluence area in Lake Chaohu (China). Both the nutrients and hazardous pollutants were analysed. Most sediment cores showed large variations in nutrient concentrations at depths of 10 to 18 cm. Positive release rates of NH4(+)-N and PO4(3-)-P were detected in sediment cores. Hg and Cd were the most typical problematic metal contaminants encountered, and their contamination levels extended to depths of 20 and 25 cm, respectively. Polycyclic aromatic hydrocarbons (mostly acenaphthene and fluorine) were the primary persistent organic pollutants (POPs) present in sediments, and contamination levels frequently could be detected up to a depth of 16 cm. Simulated dredging operations were implemented in the laboratory, with a dredging depth of 15 cm found to be suitable for nutrient suppression. With the goal of suppressing nutrients release and removing high-risk metals and POPs, a multi-objective dredging plan was developed. This plan subdivides the confluence area into five parts that were treated with different dredging depths. A demonstration area was dredged in the most heavily polluted part, and the observed dredging effects were consistent with those expected on the basis of the plan. Such an approach to dredging might also be useful in other areas in the future. PMID- 26162443 TI - Temporal variation of heavy metal accumulation and translocation characteristics of narrow-leaved cattail (Typha angustifolia L.). AB - The aim of this study was to investigate seasonal heavy metal accumulation and translocation characteristics of the narrow-leaved cattail (Typha angustifolia L.). Sediment and plant samples were taken seasonally from six different locations identified for this purpose, and Pb, Cr, Cu, Ni, Zn, and Cd concentrations as well as accumulation factor (AF) and translocation factor (TF) values were determined. It was noted that the metal concentrations in the plant roots, rhizomes, and leaves differed seasonally. The metals mainly accumulated in the plant roots, and Zn was the element that accumulated the most in the plant roots, rhizomes, and leaves. The highest Zn concentration was observed to be 56.47 MUg g(-1) in the rhizome sample from the summer. In all the seasons, the AF value of Cd was observed to be above 1. In addition, the TF value was below 1 for all elements in every season. While the element having lowest uptake and translocation ratio was Cr, and the highest uptake and translocation ratio was found for Cd. The AF and TF values suggest that the plant would be most appropriate for use in phytostabilization. PMID- 26162444 TI - Ecosystem functioning approach applied to a large contaminated coastal site: the study case of the Mar Piccolo of Taranto (Ionian Sea). AB - Knowledge on ecosystem functioning can largely contribute to promote ecosystem based management and its application. The Mar Piccolo of Taranto is a densely populated area at a high risk of environmental crisis. Here, planktonic primary production (PP) and heterotrophic prokaryotic production (HPP) were measured as proxies of functioning in three sampling sites located in two inlets at different levels of industrial contamination, during three sampling surveys (June 2013, February and April 2014). To have a better overall view and provide some insights into the benthic-pelagic coupling, we integrated PP and HPP in the water column with those in the sediments and then discussed this with the origin of the organic matter pools based on analysis of stable isotopes. Heavy metals and polychlorobiphenyls (PCBs) were also analysed in the surface (1 cm) sediment layer and related to the overall ecosystem functioning. Multidimensional scaling (MDS) analysis, based on the main data, clearly separated the second inlet from the first one, more severely impacted by anthropogenic activities. The stable isotope mixing model suggested the prevalent terrestrial/riverine origin of the particulate organic matter pools (mean 45.5 %) in all sampling periods, whereas phytoplankton contributed up to 29 % in February. Planktonic PP and HPP rates followed the same pattern over the entire study period and seemed to respond to phytoplankton dynamics confirming this community as the main driver for the C cycling in the water column. On the contrary, benthic PP rates were almost negligible while HPP rates were lower or comparable to those in the water column indicating that although the Mar Piccolo is very shallow, the water column is much more productive than the surface sediments. The sediment resuspension is likely responsible for a pulsed input of contaminants into the water column. However, their interference with the proper functioning of the pelagic ecosystem seems to be limited to the bottom layers. PMID- 26162445 TI - Malathion-induced hepatotoxicity in male Wistar rats: biochemical and histopathological studies. AB - The increasing use of organophosphorus pesticides in the environment constitutes an ecotoxicological hazard especially for humans and non-target animals. Hereby, we analyzed the toxic effects of malathion on the histological structure of liver and biochemical parameters in male rats. Three groups received daily different amounts of malathion: 1/1000, 1/100, and 1/10 LD50 for 30 days. The weights of treated rat's liver have increased. Analyzed tissues showed centrilobular and sinusoidal congestion, hepatocyte hypertrophy, cellular vacuolization, anucleated hepatocytes, depletion of organelles affecting the majority of cells, and presence of necrotic foci into the hepatic parenchyma. Histological sections of the liver showed important hepatocyte glycogen storage. We conclude that malathion stimulates the filing of glycogen in a dose-dependent manner. Biochemical parameters showed that alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels increased in the treated groups when the level of total protein decreased in intoxicated groups. PMID- 26162446 TI - Concomitant evaluation of atmospheric levels of polychlorinated biphenyls, organochlorine pesticides, and polycyclic aromatic hydrocarbons in Strasbourg (France) using pine needle passive samplers. AB - In this study, pine needles were used as cost-effective and reliable passive bio monitors to concomitantly evaluate atmospheric concentrations of three classes of persistent organic pollutants, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polycyclic aromatic hydrocarbons (PAHs). The extraction of persistent organic pollutants (POPs) from needle samples was performed. Eleven PCBs, 11 OCPs, and 15 PAHs were detected and followed through time in needle samples from three sites in the Strasbourg region. The urban and rural sites were more exposed to PCBs than the suburban site. The highest concentration of PCBs was found at the urban site, but the largest number of congeners (10) was detected at the rural site. PCB 189 and 156 were the predominant congeners in the rural site and PCB 70 in the urban site. For OCPs, the rural site displayed the highest concentrations (up to 22.9 ng g(-1)) and number of compounds investigated (9). The high concentration of gamma- and beta-hexachlorocyclohexane (HCH) at that time in the urban site was the reason for this result. gamma- and beta-HCH were the two predominant compounds in all samples. The suburban and urban sites were the most exposed with PAHs with pyrene, phenanthrene, and acenaphthene being the three predominant compounds in these sites. No specific trend in terms of time was apparent for PCBs and OCPs. However, higher concentrations were detected for some compounds in the first sampling, especially for PAHs, and this is attributed to variations in meteorological conditions (e.g., temperature, wind, rain) and variable inputs from both identified and unidentified sources. PMID- 26162448 TI - Erratum to: Occurrence of organotin compounds in river sediments under the dynamic water level conditions in the Three Gorges Reservoir Area, China. PMID- 26162447 TI - Efficient degradation of trichloroethylene in water using persulfate activated by reduced graphene oxide-iron nanocomposite. AB - Graphene oxide (GO) and nano-sized zero-valent iron-reduced graphene oxide (nZVI rGO) composite were prepared. The GO and nZVI-rGO composite were characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), energy dispersive spectroscopy (EDS), and Raman spectroscopy. The size of nZVI was about 6 nm as observed by TEM. The system of nZVI-rGO and persulfate (PS) was used for the degradation of trichloroethylene (TCE) in water, and showed 26.5% more efficiency as compared to nZVI/PS system. The different parameters were studied to determine the efficiency of nZVI-rGO to activate the PS system for the TCE degradation. By increasing the PS amount, TCE removal was also improved while no obvious effect was observed by varying the catalyst loading. Degradation was decreased as the TCE initial concentration was increased from 20 to 100 mg/L. Moreover, when initial solution pH was increased, efficiency deteriorated to 80%. Bicarbonate showed more negative effect on TCE removal among the solution matrix. To better understand the effects of radical species in the system, the scavenger tests were performed. The *SO4(-) and *O2(-) were predominant species responsible for TCE removal. The nZVI-rGO-activated PS process shows potential applications in remediation of highly toxic organic contaminants such as TCE present in the groundwater. Graphical abstract Persulfate activated by reduced graphene oxide and nano-sized zero-valent iron composite can be used for efficient degradation of trichloroethylene (TCE) in water. PMID- 26162449 TI - Endoscopic epiglottopexy using Lichtenberger's needle carrier to avoid breakdown of repair. AB - Severe type III laryngomalacia LM is represented by a retroflexed epiglottis that touches the posterior pharyngeal wall and obstructs the laryngeal inlet. Endoscopic epiglottopexy is advised in such cases wherein pexy sutures are passed between the epiglottis and base of tongue. Using conventional needle carriers, it is difficult to pass such sutures that go deep enough into the tongue base. Such a pexy is prone to a break down. We describe a novel technique of placing these glossoepiglottic sutures using the Lichtenberger's needle carrier. We used this technique in three patients with excellent results and report no complications. We propose to use this technique in cases of epiglottic prolapse seen in severe LM and certain hypotonic conditions. PMID- 26162450 TI - Exploring the feasibility of smart phone microphone for measurement of acoustic voice parameters and voice pathology screening. AB - The objective of this study is to evaluate the reliability of acoustic voice parameters obtained using smart phone (SP) microphones and investigate the utility of use of SP voice recordings for voice screening. Voice samples of sustained vowel/a/obtained from 118 subjects (34 normal and 84 pathological voices) were recorded simultaneously through two microphones: oral AKG Perception 220 microphone and SP Samsung Galaxy Note3 microphone. Acoustic voice signal data were measured for fundamental frequency, jitter and shimmer, normalized noise energy (NNE), signal to noise ratio and harmonic to noise ratio using Dr. Speech software. Discriminant analysis-based Correct Classification Rate (CCR) and Random Forest Classifier (RFC) based Equal Error Rate (EER) were used to evaluate the feasibility of acoustic voice parameters classifying normal and pathological voice classes. Lithuanian version of Glottal Function Index (LT_GFI) questionnaire was utilized for self-assessment of the severity of voice disorder. The correlations of acoustic voice parameters obtained with two types of microphones were statistically significant and strong (r = 0.73-1.0) for the entire measurements. When classifying into normal/pathological voice classes, the Oral-NNE revealed the CCR of 73.7% and the pair of SP-NNE and SP-shimmer parameters revealed CCR of 79.5%. However, fusion of the results obtained from SP voice recordings and GFI data provided the CCR of 84.60% and RFC revealed the EER of 7.9%, respectively. In conclusion, measurements of acoustic voice parameters using SP microphone were shown to be reliable in clinical settings demonstrating high CCR and low EER when distinguishing normal and pathological voice classes, and validated the suitability of the SP microphone signal for the task of automatic voice analysis and screening. PMID- 26162451 TI - Evaluation of nasal mucociliary activity in patients with chronic renal failure. AB - The ability of respiratory mucosal surfaces to eliminate foreign particles and pathogens and to keep mucosal surfaces moist and fresh depends on mucociliary activity. Chronic renal failure (CRF) is an irreversible medical condition that may result in important extrarenal systemic consequences, such as cardiovascular, metabolic, and respiratory system abnormalities. Although there are studies describing nasal manifestations of CRF, data are lacking concerning the effects of the condition on nasal mucosa. The goal of the current study was to evaluate nasal mucociliary clearance (NMC) time in patients with CRF. This prospective cohort study conducted in a tertiary referral center included 32 non-diabetic end stage CRF patients and 30 control individuals. The control group consisted of voluntary participants who had been referred to our clinic for symptoms other than rhinological diseases. The mean NMC times in CRF patients and control individuals were 12.51 +/- 3.74 min (range 7-22 min) and 8.97 +/- 1.83 min (range 6-13 min), respectively. The mean NMC time in patients with CRF was significantly longer than that in control individuals (p < 0.001). Clinicians must keep in mind that NMC time in CRF patients is prolonged and must follow-up these patients more closely for sinonasal and middle ear infections. PMID- 26162452 TI - An absorbable thread suture technique to treat snoring. AB - We investigated a novel, minimally invasive surgery that uses an absorbable suture technique to treat snoring and mild obstructive sleep apnea. This simple procedure was developed to increase the stiffness of the soft palate and to promote uvula elevation with sutures. Thirty-five snorer and mild obstructive sleep apnea syndrome patients were included in this study. The palate was sutured with the newly developed technique. The results of our surgery were evaluated using polysomnography (PSG), the Epworth sleepiness scale (ESS), and a visual analogue scale (VAS) before surgery and 90 days after surgery. One year after surgery, telephone interviews were performed to assess patient satisfaction. Postoperative physical examinations of all patients showed increased stiffness of the soft palate and superiorly displaced uvula. These findings were consistent after the postoperative day 90. The patients' snoring symptoms and their bed partners' complaints, assessed by ESS and VAS, significantly improved compared to the pre-treatment value (p < 0.05). Additionally, the apnea-hypopnea index (AHI), assessed by PSG, was significantly improved compared to the pre-treatment value (p < 0.05). Based on the results from the telephone interviews analyzed 1 year after surgery, about 88 % of patients were satisfied with the outcome. This minimally invasive snoreplasty that uses absorbable suture material is an effective and simple procedure for treating snoring and mild obstructive sleep apnea. PMID- 26162454 TI - On White Papers and Pages. PMID- 26162453 TI - Response-guided therapy of regimens based on PEG-interferon for chronic hepatitis B using on-treatment hepatitis B surface antigen quantification: a meta-analysis. AB - PURPOSE: The efficacy of on-treatment hepatitis B surface antigen (HBsAg) levels in guiding pegylated interferon (PEG-IFN) therapy for chronic hepatitis B (CHB) infections is still controversial. The aim of this study is to quantitatively evaluate the efficacy of on-treatment HBsAg levels as a response-guided therapy strategy to guide PEG-IFN-based therapies for CHB. METHODS: We searched PUBMED, EMBASE, and the Cochrane Library (1997-2013) for clinical research involving HBsAg quantification, and the response to PEG-IFN-based therapy. Pooled effect of HBsAg levels on guiding PEG-IFN-based therapies for CHB was evaluated using fixed effects or random-effects model. RESULTS: From 13 studies (n = 1493 patients), patients with optimal on-treatment HBsAg levels were found to have a greater chance of attaining a response (RR 5.17, 95 % CI 3.75-7.11, p < 0.00001), and the pooled total response rate was 54 % (95 % CI 44-63 %). At week 12, patients without optimal on-treatment HBsAg levels had hardly achieved a response (the early non-response rate: 99 %, 95 % CI 98-100 %). At 24 weeks, the response rate increased to 79 % in HBeAg-negative patients. CONCLUSION: This meta-analysis suggested that on-treatment HBsAg quantification is effective in guiding the therapy of PEG-IFN in CHB infections, especially in HBeAg-negative patients. PMID- 26162455 TI - Development of the Nurse Practitioner Standards for Practice Australia. AB - This article describes the context and development of the new Nurse Practitioner Standards for Practice in Australia, which went into effect in January 2014. The researchers used a mixed-methods design to engage a broad range of stakeholders who brought both political and practice knowledge to the development of the new standards. Methods included interviews, focus groups, surveys, and work-based observation of nurse practitioner practice. Stakeholders varied in terms of their need for detail in the standards. Nonetheless, they invariably agreed that the standards should be clinically focussed attributes. The pillars common in many advanced practice nursing standards, such as practice, research, education, and leadership, were combined and expressed in a new and unique clinical attribute. PMID- 26162457 TI - Monitoring Tumor Targeting and Treatment Effects of IRDye 800CW and GX1 Conjugated Polylactic Acid Nanoparticles Encapsulating Endostar on Glioma by Optical Molecular Imaging. AB - Molecular imaging used in cancer diagnosis and therapeutic response monitoring is important for glioblastoma (GBM) research. Antiangiogenic therapy currently is one of the emerging approaches for GBM treatment. In this study, a multifunctional nanoparticle was fabricated that can facilitate the fluorescence imaging of tumor and deliver a therapeutic agent to the tumor region in vivo and therefore possesses broad application in cancer diagnosis and treatment. This particle was polylactic acid (PLA) nanoparticles encapsulating Endostar, which was further conjugated with GX1 peptide and the near-infrared (NIR) dye IRDye 800CW (IGPNE). We demonstrated noninvasive angiogenesis targeting and therapy of IGPNE on U87MG xenografts in vivo using dual-modality optical molecular imaging including NIR fluorescence molecular imaging (FMI) and bioluminescence imaging (BLI). The NIR FMI results demonstrated that IGPNE had more accumulation to the tumor site compared to free IRDye 800CW. To further evaluate the antitumor treatment efficacy of IGPNE, BLI and immunohistochemistry analysis were performed on tumor-bearing mice. With the aid of molecular imaging, the results confirmed that IGPNE enhanced antitumor treatment efficacy compared to free Endostar. In conclusion, IGPNE realizes real-time imaging of U87MG tumors and improves the antiangiogenic therapeutic efficacy in vivo. PMID- 26162456 TI - Monoselective o-C-H Functionalizations of Mandelic Acid and alpha-Phenylglycine. AB - Pd-catalyzed C-H functionalization of mandelic acid and alpha-phenylglycine is reported. We have developed different protocols for the arylation, iodination, acetoxylation, and olefination of these substrates based on two different (Pd(II)/Pd(IV) and Pd(II)/Pd(0)) catalytic cycles. Four crucial features of these protocols are advantageous for practical applications. First, the alpha-hydroxyl and amino groups are protected with simple protecting groups such as acetates (Ac, Piv) and carbamates (Boc, Fmoc), respectively. Second, these protocols do not involve installation and removal of a directing group. Third, monoselectivity is accomplished. Fourth, no epimerization occurs at the vulnerable alpha-chiral centers. PMID- 26162458 TI - A budget impact model for biosimilar infliximab in Crohn's disease in Bulgaria, the Czech Republic, Hungary, Poland, Romania, and Slovakia. AB - OBJECTIVES: To estimate the budget impact of the introduction of biosimilar infliximab for the treatment of Crohn's disease (CD) in Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. METHODS: A 3-year, prevalence based budget impact analysis for biosimilar infliximab to treat CD was developed from third-party payers' perspective. The model included various scenarios depending on whether interchanging originator infliximab with biosimilar infliximab was allowed or not. RESULTS: Total cost savings achieved in biosimilar scenario 1 (interchanging not allowed) and BSc2 (interchanging allowed in 80% of the patients) were estimated to ?8.0 million and ?16.9 million in the six countries. Budget savings may cover the biosimilar infliximab therapy for 722 1530 additional CD patients. CONCLUSIONS: Introduction of biosimilar infliximab to treat CD may offset the inequity in access to biological therapy for CD between Central and Eastern European countries. PMID- 26162459 TI - Depression and Altitude: Cross-Sectional Community-Based Study Among Elderly High Altitude Residents in the Himalayan Regions. AB - Suicide rates are higher at high altitudes, and some hypothesize that hypoxia is the cause. There may be a significant correlation between rates of depression and altitude, but little data exist outside the United States. The purpose of the present study is to conduct a survey of depression among the elderly highlanders in Asia. We enrolled 114 persons aged 60 years or older (mean, 69.2 +/- 6.7 years; women, 58.8%) in Domkhar (altitude, 3800 m), Ladakh, India and 173 ethnic Tibetans (mean, 66.5 +/- 6.1 years; women, 61.3%) in Yushu (altitude, 3700 m), Qinghai Province, China. The two-item Patient Health Questionnaire (PHQ-2) and the geriatric depression scale were administered. A psychiatrist interviewed the subjects who had a positive score on the PHQ-2. The results of the interview with the residents conducted by the specialist showed that two cases (1.8%) from Domkhar and four (2.3%) from Qinghai had depression. Despite the high altitude, the probability of depression was low in elderly highlander in Ladakh and Qinghai. Our finding seems to indicate that cultural factors such as religious outlook and social/family relationship inhibit the development of depression. PMID- 26162461 TI - Simulating uterine contraction by using an electro-chemo-mechanical model. AB - Contractions of uterine smooth muscle cells consist of a chain of physiological processes. These contractions provide the required force to expel the fetus from the uterus. The inclusion of these physiological processes is, therefore, imperative when studying uterine contractions. In this study, an electro-chemo mechanical model to replicate the excitation, activation, and contraction of uterine smooth muscle cells is developed. The presented modeling strategy enables efficient integration of knowledge about physiological processes at the cellular level to the organ level. The model is implemented in a three-dimensional finite element setting to simulate uterus contraction during labor in response to electrical discharges generated by pacemaker cells and propagated within the myometrium via gap junctions. Important clinical factors, such as uterine electrical activity and intrauterine pressure, are predicted using this simulation. The predictions are in agreement with clinically measured data reported in the literature. A parameter study is also carried out to investigate the impact of physiologically related parameters on the uterine contractility. PMID- 26162462 TI - A Transition to Residency Curriculum for International Medical Graduate Psychiatry Trainees. PMID- 26162463 TI - Managing Stigma Effectively: What Social Psychology and Social Neuroscience Can Teach Us. AB - Psychiatric education is confronted with three barriers to managing stigma associated with mental health treatment. First, there are limited evidence-based practices for stigma reduction, and interventions to deal with stigma against mental health care providers are especially lacking. Second, there is a scarcity of training models for mental health professionals on how to reduce stigma in clinical services. Third, there is a lack of conceptual models for neuroscience approaches to stigma reduction, which are a requirement for high-tier competency in the ACGME Milestones for Psychiatry. The George Washington University (GWU) psychiatry residency program has developed an eight-week course on managing stigma that is based on social psychology and social neuroscience research. The course draws upon social neuroscience research demonstrating that stigma is a normal function of normal brains resulting from evolutionary processes in human group behavior. Based on these processes, stigma can be categorized according to different threats that include peril stigma, disruption stigma, empathy fatigue, moral stigma, and courtesy stigma. Grounded in social neuroscience mechanisms, residents are taught to develop interventions to manage stigma. Case examples illustrate application to common clinical challenges: (1) helping patients anticipate and manage stigma encountered in the family, community, or workplace; (2) ameliorating internalized stigma among patients; (3) conducting effective treatment from a stigmatized position due to prejudice from medical colleagues or patients' family members; and (4) facilitating patient treatment plans when stigma precludes engagement with mental health professionals. This curriculum addresses the need for educating trainees to manage stigma in clinical settings. Future studies are needed to evaluate changes in clinical practices and patient outcomes as a result of social neuroscience-based training on managing stigma. PMID- 26162465 TI - Stress-echocardiography is underused in clinical practice: a nationwide survey in Austria. AB - BACKGROUND: The wide area of application, including coronary artery disease, valvular heart disease, or pulmonary hypertension makes stress echocardiography (SE) a powerful, cost-effective imaging modality in cardiology. The role of this technique in clinical practice in Austria is unknown. METHODS: A nationwide survey included all departments for cardiology and/or internal medicine in the years 2008 and 2013. By electronic questionnaire demographics, indication for the test, the numbers of examined cases per year, operators, and various applied techniques of SE were interrogated and completed by telephone interviews. RESULTS: Data could be obtained from all 117 departments. In the year 2007 in 58 (50%) and in 2012 57 (49%) departments SE was available in Austrian hospitals. More than 100 SEs per year were performed by only four (7%) units in the year 2007 and by five (8%) in 2012. Physical exercise, dobutamine, and dipyridamole SE were available in 27 (46%), 52 (90%), and six (10%) units in 2007, and in 15 (27%), 52 (91%), and five (9%) units in 2012, respectively. In 2007 41 (71%) and in 2012 26 (46%) echo-labs administered contrast agents during SE. Transesophageal SE and 3D-echo was performed in one (2%) and three (5%) units in 2007, and in six (10%) and four (7%) echo-labs in 2012. CONCLUSIONS: This representative survey demonstrates the underuse of SE in clinical practice in Austria. Even in established application fields performance is low, examination frequencies as recommended by the cardiology societies are fulfilled only by a minority of institutions. PMID- 26162464 TI - One-year mortality in patients with acute ST-elevation myocardial infarction in the Vienna STEMI registry. AB - BACKGROUND AND AIM: Systems of care to treat acute ST-elevation myocardial infarction (STEMI) have been developed world wide in the past decade. Their effectiveness can only be proven by including and analyzing outcome data of consecutive patients in registries, which is not the case in the majority of STEMI networks. This study investigates 1-year mortality in STEMI patients in Vienna included over a 14 months time interval. The Vienna STEMI network is organized by a specific rotational system and offers both, primary percutaneous intervention (PPCI) and thrombolytic therapy (TT) as reperfusion strategies according to the recent guidelines. METHODS: At the time of investigation, the Vienna STEMI network consisted of the Viennese Ambulance Systems and five high volume interventional cardiology departments. This network has been organized in order to increase the number of STEMI patients admitted for PPCI and to offer the fastest available reperfusion strategy, in the majority PPCI but in selected patients also TT (STEMI of short duration, mainly anterior wall MI and mainly patients younger than 75 years), followed by rescue PCI in non-responders and elective angiography with/without PCI in responders to TT during the index hospital stay. RESULTS: One-year all-cause mortality rates in the Vienna STEMI network by use of the fastest available reperfusion strategy were 13.4% in patients who received reperfusion therapy after 2 h of symptom onset and 7.4% in patients treated within 2 h; (p = 0.017). Whereas PPCI and TT demonstrated a nonsignificant difference in 1-year mortality rates when initiated within 2 h of symptom onset (10.0% vs 5.7%; p = 0.59), PPCI was more effective in acute STEMI of > 2 h duration as compared to TT but this difference did not reach statistical significance (12.1% vs 18.2%; p = 0.07). CONCLUSIONS: The reassuring long-term results of the Viennese STEMI network are another example of a specific regional system of care to offer timely diagnosis, transfer and reperfusion in patients with STEMI. In contrast to other metropolitan areas where TT has almost completely abandoned, we still use pharmacological reperfusion as a backup in case of expected and unacceptable time delays for PPCI in order to reduce myocardial damage especially in patients with larger infarctions of short duration with a low risk of bleeding complications. PMID- 26162466 TI - Imaging of childhood angiomatoid fibrous histiocytoma with pathological correlation. AB - BACKGROUND: Angiomatoid fibrous histiocytoma is a rare soft-tissue tumor that more often affects children and young adults. There is little information available regarding the imaging appearance of angiomatoid fibrous histiocytoma in children. OBJECTIVE: To describe the ultrasonographic (US) and magnetic resonance (MR) imaging findings of angiomatoid fibrous histiocytoma in children. MATERIALS AND METHODS: A retrospective analysis was done of US and MR imaging findings in children with angiomatoid fibrous histiocytoma. Clinical findings and histopathology with molecular analysis results were also collected. RESULTS: There were 7 children with angiomatoid fibrous histiocytoma with a median age of 6 years (age range: 16 months-14 years). Patients presented clinically with a soft-tissue mass in the extremities or in the trunk. Four children had anemia, and three of them had additional systemic symptoms. Two patients had US and three had MR imaging while the remaining two had both. Lesion size ranged from 1.3 cm to 7.2 cm. In four patients, angiomatoid fibrous histiocytoma presented as a nonspecific predominantly solid mass. The other three patients had a combination of the following imaging findings: intralesional blood-filled cystic spaces with fluid-fluid levels, enhancing fibrous pseudocapsule and hemosiderin deposition. These findings correlated well with histopathology. CONCLUSION: The imaging detection of intralesional blood-filled cystic spaces with fluid-fluid levels, enhancing fibrous pseudocapsule and hemosiderin deposition in a soft-tissue tumor in a child may suggest the diagnosis of angiomatoid fibrous histiocytoma. A history of systemic symptoms and anemia in the presence of a soft-tissue mass may also be a clue for the diagnosis of angiomatoid fibrous histiocytoma. PMID- 26162467 TI - Chemotherapy-related complications in the kidneys and collecting system: an imaging perspective. AB - Nephrotoxicity is a common adverse effect of many chemotherapeutic agents. The agents most commonly associated with chemotherapy-associated nephrotoxicity are methotrexate, semustine, streptozocin, mithramycin, and cisplatin. Certain chemotherapeutic agents have adverse effects on the kidneys and urothelium that can be visualized radiographically, including cystic change, interstitial nephritis, papillary necrosis, urothelial changes, haemorrhagic cystitis, acute tubular necrosis, and infarction. This review focuses on imaging features identifying complications of chemotherapy in the kidneys and collecting system and provides didactic cases to alert referring clinicians. TEACHING POINTS: * Nephrotoxicity is a common adverse effect of many chemotherapeutic agents. * Chemotherapies have adverse renal and urothelial effects that can be visualized radiographically. * Crizotinib use can result in the development of complex renal cysts. PMID- 26162468 TI - Metastatic sympathetic paraganglioma in a patient with loss of the SDHC gene. AB - Mutation of the genes encoding the succinate dehydrogenase (SDH) subunits A, B, C, or D, or the SDHAF2 protein, cause the SDHx-hereditary paraganglioma syndromes. Hereditary susceptibility to metastatic sympathetic pheochromocytomas and paragangliomas is most commonly due to germline mutations in the SDHB gene. Individuals with SDHD mutations occasionally present with metastatic disease, while conversely malignant paragangliomas are rarely observed in SDHC carriers. A 43 year-old woman presented with an abdominal paraganglioma metastatic to the skeleton and multiple lymph nodes. The tumor produced excessive amounts of noradrenaline causing hypertension and symptoms of catecholamine excess. The patient underwent surgical resection of the primary tumor and lymph node metastases. Loss of SDHB protein expression in the primary tumor was demonstrated by immunohistochemistry. Germline sequencing and deletion testing revealed a large allelic deletion of exons 1-6 in SDHC, and no mutations or deletions were detected in SDHB or SDHD. The patient's mother died because of kidney cancer. Hereditary pheochromocytomas and paragangliomas may be associated with a deletion of the SDHC gene. These patients may present with malignant sympathetic paragangliomas. PMID- 26162469 TI - Comparison of different blood compartments for the detection of circulating DNA using a rat model of Pneumocystis pneumonia. AB - Pneumocystis is mostly found in the alveolar spaces, but circulation of viable organisms also occurs and suggests that the detection of DNA in blood could be used as a noninvasive procedure to improve the diagnosis of Pneumocystis pneumonia (PcP). In order to determine the optimal compartment for Pneumocystis DNA detection, we used a rat model of PcP and tested the presence of Pneumocystis with a quantitative mtLSU targeting real-time PCR in four blood compartments: whole blood, clot, serum and Platelet-Rich-Plasma (PRP). All samples from 4 Pneumocystis-free control rats were negative. Pneumocystis was detected in 79, 64, 57, and 57% of samples from 14 PcP rats, respectively, but DNA release was not related to pulmonary loads. These data confirm the potential usefulness of Pneumocystis DNA detection in the blood for PcP diagnosis and suggest that whole blood could be the most appropriate compartment for Pneumocystis detection. PMID- 26162470 TI - Effect of tyrosol on adhesion of Candida albicans and Candida glabrata to acrylic surfaces. AB - The prevention of adhesion of Candida cells to acrylic surfaces can be regarded as an alternative to prevent denture stomatitis. The use of quorum sensing molecules, such as tyrosol, could potentially interfere with the adhesion process. Therefore, the aim of this study was to assess the effect of tyrosol on adhesion of single and mixed cultures of Candida albicans and Candida glabrata to acrylic resin surfaces. Tyrosol was diluted in each yeast inoculum (10(7) cells/ml in artificial saliva) at 25, 50, 100, and 200 mM. Then, each dilution was added to wells of 24-well plates containing the acrylic specimens, and the plates were incubated at 37 degrees C for 2 h. After, the effect of tyrosol was determined by total biomass quantification, metabolic activity of the cells and colony-forming unit counting. Chlorhexidine gluconate (CHG) was used as a positive control. Data were analyzed using analysis of variance (ANOVA) and the Holm-Sidak post hoc test (alpha = 0.05). The results of total biomass quantification and metabolic activity revealed that the tyrosol promoted significant reductions (ranging from 22.32 to 86.16%) on single C. albicans and mixed cultures. Moreover, tyrosol at 200 mM and CHG significantly reduced (p < 0.05) the number of adhered cells to the acrylic surface for single and mixed cultures of both species, with reductions ranging from 1.74 to 3.64-log10. In conclusion, tyrosol has an inhibitory effect on Candida adhesion to acrylic resin, and further investigations are warranted to clarify its potential against Candida infections. PMID- 26162471 TI - Combining Aspergillus mitochondrial and ribosomal QPCR, in addition to galactomannan assay, for early diagnosis of invasive aspergillosis in hematology patients. AB - The combination of two quantitative Aspergillus PCR assays, targeting a mitochondrial and a ribosomal target (AfQPCR), has proved effective for diagnosing invasive aspergillosis (IA) in hematology patients with risk factors and a positive galactomannan antigen (GM). The aim of the present study was to assess the performance of systematic AfQPCR for IA screening in at risk patients in a hematology intensive care unit (ICU). The study was performed in the hematology ICU at Besancon University Hospital from March 2012 to December 2013. GM detection (Platelia Aspergillus, Biorad, France) and AfQPCR were performed on the same serum sample, twice a week, in all patients with risk factors for IA. Risk factors and clinical, radiological, and biological data were prospectively recorded using the information sheet from the French network for the surveillance of Invasive Fungal Infection. Thirty-two patients were diagnosed with proven, probable, or possible IA according to the 2008 EORTC/MSG criteria. Sixteen patients had a positive AfQPCR: 9/16 had a positive GM at the same time (GM index >0.5), 4/16 had a positive GM before the AfQPCR and 3/16 had a negative GM at the time of the positive AfQPCR. Screening at risk patients using both AfQPCR and GM on the same serum sample is very feasible in a routine clinical setting. Our results confirm the usefulness of combining biomarkers for an early IA diagnosis. PMID- 26162472 TI - Azole susceptibility of Malassezia pachydermatis and Malassezia furfur and tentative epidemiological cut-off values. AB - This study aims to determine the minimal inhibitory concentration (MIC) distribution and the epidemiological cut-off values (ECVs) of Malassezia pachydermatis and Malassezia furfur isolates for fluconazole (FLZ), itraconazole (ITZ), posaconazole (POS), and voriconazole (VOR). A total of 62 M. pachydermatis strains from dogs with dermatitis and 78 M. furfur strains from humans with bloodstream infections (BSI) were tested by a modified broth microdilution Clinical and Laboratory Standards Institute (CLSI) method. ITZ and POS displayed lower MICs than VOR and FLZ, regardless of the Malassezia species. The MIC data for azoles of M. pachydermatis were four two-fold dilutions lower than those of M. furfur. Based on the ECVs, about 94% of Malassezia strains might be categorized within susceptible population for all azoles, except for FLZ, and azole cross-resistance was detected in association with FLZ in M. pachydermatis but not in M. furfur.The study proposes, for the first time, tentative azole ECVs for M. pachydermatis and M. furfur for monitoring the emergence of isolates with decreased susceptibilities and shows that the azole MIC distribution varied according to the Malassezia species tested, thus suggesting the usefulness of determining the susceptibility profile for effective treatment of each species. PMID- 26162473 TI - In vitro interactions between amphotericin B and hydrocortisone: potential implications for intrathecal therapy. AB - Fungal meningitis remains a severe and often lethal infection requiring aggressive antifungal therapy and in refractory cases the use of intrathecal amphotericin B (AmB). Administration of amphotericin B by this method may result in clinically apparent adverse reactions such as paresthesias, radiculitis, or myelopathy. Coadministration of hydrocortisone is therefore often given in an attempt to avoid these effects; however, the potential consequences of this approach on fungal growth or on drug synergy/antagonism had not previously been assessed. We used the checkerboard titration broth microdilution method to analyze interactions by fractional inhibitory concentration indices (FICIs). The combination of amphotericin B and hydrocortisone resulted in synergy or indifference against all isolates (Candida, Cryptococcus, and Coccidioides) during in vitro testing at low concentrations. Antagonism was observed using higher hydrocortisone concentrations (those not observed in vivo) suggesting possible steric hindrance or binding to AmB may occur at doses unlikely to be present during clinical care. Concurrent hydrocortisone and AmB administration should not be avoided due to in vitro antagonism concerns. PMID- 26162474 TI - Detection of triazole resistance among Candida species by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). AB - MALDI-TOF MS can rapidly identify microorganisms to the species level and may be able to detect antimicrobial resistance. We evaluated the ability of this technology to detect triazole resistance in Candida species.35 C. albicans, 35 C. glabrata, and 37 C. tropicalis strains were exposed to fluconazole, voriconazole, or posaconazole at two different concentrations plus a drug-free control: a midrange concentration (CLSI clinical breakpoint or epidemiologic cut-off value), and a high concentration (fluconazole 64 MUg/ml, voriconazole & posaconazole 16 MUg/ml). The MALDI-TOF MS spectra at these concentrations were used to create the individual composite correlation index (CCI) matrices for each isolate. When the CCI of the midrange/highest concentration was lower than that of the midrange/null concentration, the strain was classified as resistant. These results were then compared to the classifications for susceptible or resistant obtained by measuring the MICs according to the CLSI M27-A3 antifungal susceptibility testing (AFST) method.The MALDI-TOF MS assay was able to classify triazole susceptibility against all strains. Overall, essential agreement between MALDI-TOF MS and AFST varied between 54% and 97%, and was highest for posaconazole against C. glabrata. The reproducibility of the MALDI-TOF MS assay varied between 54.3 and 82.9% and was best for fluconazole against C. albicans and posaconazole against C. glabrata. Reproducibility was also higher for C. glabrata isolates compared to C. albicans and C. tropicalis.These results demonstrate that MALDI-TOF MS may be used to simultaneously determine the Candida species and classification as susceptible or resistant to triazole antifungals. Further studies are needed to refine the methodology and improve the reproducibility of this assay. PMID- 26162475 TI - Aspergillus fumigatus enhances elastase production in Pseudomonas aeruginosa co cultures. AB - In the cystic fibrosis (CF) lung the presence of bacteria and fungi in the airways promotes an inflammatory response causing progressive lung damage, ultimately leading to high rates of morbidity and mortality. We hypothesized that polymicrobial interactions play an important role in promoting airway pathogenesis. We therefore examined the interplay between the most commonly isolated bacterial CF pathogen, Pseudomonas aeruginosa, and the most prevalent filamentous fungi, Aspergillus fumigatus, to test this. Co-culture experiments showed that in the presence of A. fumigatus the production of P. aeruginosa elastase was enhanced. This was confirmed by the presence of zones of clearance on Elastin-Congo Red (ECR) agar, which was identified as elastase by mass spectrometry. When P. aeruginosa were grown in a co-culture model with mature A. fumigatus biofilms, 60% of isolates produced significantly more elastase in the presence of the filamentous fungi than in its absence (P < .05). The expression of lasB also increased when P. aeruginosa isolates PA01 and PA14 were grown in co culture with A. fumigatus. Supernatants from co-culture experiments were also significantly toxic to a human lung epithelial cell line (19-38% cell cytotoxicity) in comparison to supernatants from P. aeruginosa only cultures (P < .0001). Here we report that P. aeruginosa cytotoxic elastase is enhanced in the presence of the filamentous fungi A. fumigatus, suggesting that this may have a role to play in the damaging pathology associated with the lung tissue in this disease. This indicates that patients who have a co-colonisation with these two organisms may have a poorer prognosis. PMID- 26162476 TI - IgG1 anti-cell wall and IgG2 anti-phosphopeptidomannan antibodies in the diagnosis of invasive candidiasis and heavy Candida colonization. AB - We conducted a retrospective study to evaluate the usefulness of immunoglobulin G (IgG) subclasses against Candida cell wall fragments (CW) and phosphopeptidomannan (PPM) for the diagnosis of invasive candidiasis (IC). We analyzed 54 patients with IC (n = 19), Candida heavy colonization (HC; n = 16), and controls (no IC or HC, n = 19).In nonneutropenic patients (n = 47), the sensitivity and specificity values of IgG1 anti-CW and IgG2 anti-PPM in IC were 88%, 59%, and 88%, 94%, respectively. The areas under the receiver operating characteristic curves were 0.69 (0.51-0.88) and 0.901 (0.78-1.02), respectively. IgG1 mean values (arbitrary units) and 95% confidence interval were 46 (20-71), 42 (-0.38 to 84) and 20 (8.3-32) in IC, HC, and in controls, respectively, and discriminated IC but not HC from controls (P = .032, and P = .77, respectively). IgG2 mean values were 26 (9.2-42), 19 (4.4-33), and 3.2 (0.28-6.6) in IC, HC, and in controls, respectively, and discriminated both IC and HC from controls (P < .0001 and P = .035, respectively) but did not separate IC from HC (P = .2). IgG2 showed positivity as early as one day after the IC diagnosis. Antibodies were detected in only two out of a total of seven neutropenic patients.For both IC and HC patients, the diagnostic performance of IgG2 anti-PPM was better than the one of IgG1 anti-CW. In nonneutropenic patients, IgG2 anti-PPM accurately identified not only IC patients but also HC patients at high risk for IC. This marker may help clinicians in the initiation of early preemptive therapy. PMID- 26162477 TI - Source contributions and mass loadings for chemicals of emerging concern: Chemometric application of pharmaco-signature in different aquatic systems. AB - To characterize the source contributions of chemicals of emerging concern (CECs) from different aquatic environments of Taiwan, we collected water samples from different aquatic systems, which were screened for 30 pharmaceuticals and illicit drugs. The total estimated mass loadings of CECs were 23.1 g/d in southern aquatic systems and 133 g/d in central aquatic systems. We developed an analytical framework combining pollutant fingerprinting, hierarchical cluster analysis (HCA), and principal component analysis with multiple linear regression (PCA-MLR) to infer the pharmaco-signature and source contributions of CECs. Based on this approach, we estimate source contributions of 62.2% for domestic inputs, 16.9% for antibiotics application, and 20.9% for drug abuse/medication in southern aquatic system, compared with 47.3% domestic, 35.1% antibiotic, and 17.6% drug abuse/medication inputs to central aquatic systems. The proposed pharmaco-signature method provides initial insights into the profile and source apportionment of CECs in complex aquatic systems, which are of importance for environmental management. PMID- 26162478 TI - A homolog of Kunitz-type serine protease inhibitor from rock bream, Oplegnathus fasciatus: Molecular insights and transcriptional modulation in response to microbial and PAMP stimulation, and tissue injury. AB - Serine proteases and their inhibitors play vital roles in diverse biological processes. In this study, we identified and characterized cDNA coding for a Kunitz-type serine protease inhibitor (SPI), which we designated as RbKSPI, in a commercially important species, rock bream. The full-length cDNA sequence of RbKSPI consisted of 2452 bp with an open reading frame (ORF) of 1521 bp encoding a polypeptide of 507 amino acid (aa) residues. In the RbKSPI protein, MANEC, PKD, LDLa, and two Kunitz domains responsible for various functions were identified as characteristic features. Homology analysis revealed that RbKSPI shared the highest identity with the Kunitz homolog in Takifugu rubripes (77.6%). Phylogenetic analysis indicated that RbKSPI clusters with other teleostean KSPIs. In tissue-specific expression analysis, RbKSPI transcripts were detected in all the tested tissues, with the highest expression in gill tissue, followed by kidney and intestine. The mRNA expression of RbKSPI significantly increased in blood cells upon stimulation with two strains of bacteria (Edwardsiella tarda and Streptococcus iniae) and two pathogen-associated molecular patterns (PAMPs; LPS and poly I:C). Meanwhile, down-regulated expression of RbKSPI was observed in response to tissue injury. Collectively, these results suggest that the RbKSPI may be involved in essential immune defense against microbial pathogens and in the wound-healing process. PMID- 26162479 TI - Molecular markers and Schistosoma-associated bladder carcinoma: A systematic review and meta-analysis. AB - BACKGROUND: Molecular mechanisms and pathogenesis of schistosomal-associated bladder cancer (SABC), one of the most common malignancies in Africa and parts of the Middle East, is still unclear. Identification of host molecular markers involved in schistosomal related bladder carcinogenesis is of value in prediction of high-risk group, early detection and timely intervention. METHODS: PubMed, Scopus, Google Scholar, Cochrane Library and African Journals Online databases were systematically searched and reviewed. A total of 63 articles reporting 41 host molecular factors were included in the meta-analysis. RESULTS: Pooled odds ratio demonstrated associations of p53 expression, telomerase activity and sFas with SABC as compared to other schistosomal patients (p53 expression: OR=9.46, 95%CI=1.14-78.55, p=0.04; telomerase by TERT: OR=37.38, 95%CI=4.17-334.85, p=0.001; telomerase by TRAP: OR=10.36, 95%CI=6.08-17.64, p<0.00001; sFas: OR=34.37, 95%CI=3.32-355.51, p=0.003). In comparison to bladder cancers of other etiology, positive associations were found between SABC and p15 deletion, p16 deletion, telomerase activity and sFas (p15 deletion: OR=4.20, 95%CI=2.58-6.82, p<0.00001; p16 deletion: OR=4.93, 95%CI=2.52-9.65, p<0.00001; telomerase by TERT: OR=3.01, 95%CI=1.51-5.97, p=0.002; telomerase by TRAP: OR=2.66, 95%CI=1.18-6.01, p=0.02; sFas: OR=4.50, 95%CI=1.78-11.40, p=0.001). Other identified associations were reported by few numbers of studies to enable reliable interpretation. CONCLUSIONS: Variations in gene expression or genomic alterations of some molecular markers in SABC as compared to non-SABC or other schistosomal patients were identified. These suggest minute differences in the pathogenesis and physiological profile of SABC, in relation to non-SABC. PMID- 26162480 TI - Repeated cognitive stimulation alleviates memory impairments in an Alzheimer's disease mouse model. AB - Alzheimer's disease is a neurodegenerative disease associated with progressive memory and cognitive decline. Previous studies have identified the benefits of cognitive enrichment on reducing disease pathology. Additionally, epidemiological and clinical data suggest that repeated exercise, and cognitive and social enrichment, can improve and/or delay the cognitive deficiencies associated with aging and neurodegenerative diseases. In the present study, 3xTg-AD mice were exposed to a rigorous training routine beginning at 3 months of age, which consisted of repeated training in the Morris water maze spatial recognition task every 3 months, ending at 18 months of age. At the conclusion of the final Morris water maze training session, animals subsequently underwent testing in another hippocampus-dependent spatial task, the Barnes maze task, and on the more cortical-dependent novel object recognition memory task. Our data show that periodic cognitive enrichment throughout aging, via multiple learning episodes in the Morris water maze task, can improve the memory performance of aged 3xTg-AD mice in a separate spatial recognition task, and in a preference memory task, when compared to naive aged matched 3xTg-AD mice. Furthermore, we observed that the cognitive enrichment properties of Morris water maze exposer, was detectable in repeatedly trained animals as early as 6 months of age. These findings suggest early repeated cognitive enrichment can mitigate the diverse cognitive deficits observed in Alzheimer's disease. PMID- 26162482 TI - Microtubule guiding in a multi-walled carbon nanotube circuit. AB - In nanotechnological devices, mass transport can be initiated by pressure driven flow, diffusion or by employing molecular motors. As the scale decreases, molecular motors can be helpful as they are not limited by increased viscous resistance. Moreover, molecular motors can move against diffusion gradients and are naturally fitted for nanoscale transportation. Among motor proteins, kinesin has particular potential for lab-on-a-chip applications. It can be used for sorting, concentrating or as a mechanical sensor. When bound to a surface, kinesin motors propel microtubules in random directions, depending on their landing orientation. In order to circumvent this complication, the microtubule motion should be confined or guided. To this end, dielectrophoretically aligned multi-walled-carbon nanotubes (MWCNT) can be employed as nanotracks. In order to control more precisely the spatial repartition of the MWCNTs, a screening method has been implemented and tested. Polygonal patterns have been fabricated with the aim of studying the guiding and the microtubule displacement between MWCNT segments. Microtubules are observed to transfer between MWCNT segments, a prerequisite for the guiding of microtubules in MWCNT circuit-based biodevices. The effect of the MWCNT organization (crenellated or hexagonal) on the MT travel distance has been investigated as well. PMID- 26162481 TI - Impact of Perceived Barriers to Healthy Eating on Diet and Weight in a 24-Month Behavioral Weight Loss Trial. AB - OBJECTIVE: To examine longitudinal changes in perceptions of barriers to healthy eating and its impact on dietary intake and weight loss in a 24-month trial. METHODS: A secondary analysis was conducted using data from a behavioral weight loss trial (n = 210). The Barriers to Healthy Eating (BHE) scale was used to measure perceived barriers to healthy eating. Weight, total energy, and fat intake were measured. Longitudinal mixed regression modeling was used for data analysis. RESULTS: The BHE total score decreased from baseline to 6 months and increased slightly from 6 to 24 months (P < .001). Changes in BHE total and subscale scores were positively associated with changes in total energy and fat intake (P < .05) as well as weight (P < .01). CONCLUSIONS AND IMPLICATIONS: Reducing barriers could lead to improved short-term dietary changes and weight loss. Innovative strategies need to be developed to prevent barriers from increasing when intervention intensity begins to decrease. PMID- 26162483 TI - Acoustic micromixing increases antibody-antigen binding in immunoassays. AB - Sound wave-assisted acoustic micromixing has been shown to increase the binding of molecules in small volumes (10-100 MUL) where effective mixing is difficult to achieve through conventional techniques. The aim of this work is to study whether acoustic micromixing can increase the binding efficiency of antibodies to their antigens, a reaction that forms the basis of immunoassays, including enzyme linked immunosorbent assay (ELISA). Using a procedure from a general ELISA and immobilizing an antigen on wells of 96-well plates, it was found that acoustic micromixing at 125-150 Hz increased the initial rate of antibody-antigen binding by over 80 % and the total binding at the end point (i.e., 45 min) by over 50 %. As a result, acoustic micromixing achieved a binding level in 9 min that would otherwise take 45 min on a standard platform rocking mixer. Therefore acoustic micromixing has the potential to increase the detection sensitivity of ELISA as well as shorten the antigen-antibody binding times from typically 45-60 min to 15 min. PMID- 26162484 TI - Child and adolescent mental health problems in Tyva Republic, Russia, as possible risk factors for a high suicide rate. AB - High rates of child mental health problems in the Russian Federation have recently been documented; the rates of youth suicide are among the highest in the world. Across the Russian regions, Republic of Tyva has one of the highest rates of child and adolescent suicide and the lowest life expectancy at birth. The aim of this study was to investigate the prevalence and associations of mental health problems in Native Tyvinian children and adolescents using internationally recognised measures and diagnoses. A two-stage, two-phase design involved selection of schools in five rural settlements in Western Tyva and two schools in the capital city followed by selection of Native Tyvinian children in grades 3-4 (ages 9-10) and 6-7 (ages 14-15). In the first phase, a screening measure of psychopathology, the Rutter Teacher Questionnaire, was obtained on 1048 children with a 97% participation rate. In the second phase, more detailed psychiatric assessments were carried out for subgroups of screen-positive and screen-negative children. The prevalence of mental health problems was about 25%, ranging from 40% in adolescent boys from rural areas to 9% in adolescent girls from the city. The patterning of disorders and risk factors were similar to those in other countries, rural areas were associated with an increased risk of psychopathology. The findings indicate that there is an urgent need for interventions to reduce risk in this population and provide effective help for Tyvinian children and adolescents with mental health problems. PMID- 26162485 TI - Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy. AB - OBJECTIVE: To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). PATIENTS AND METHODS: In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4 10ng/ml) cohort (171 individuals). RESULTS: Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, P<0.001), as for the PCA3 score (24 vs. 54, P<0.001) and %fPSA (11.8% vs. 15.8%, P = 0.012). The net benefit of using PCA3 and PHI to differentiate prostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40% 100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. CONCLUSION: In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN. PMID- 26162486 TI - Novel and next-generation androgen receptor-directed therapies for prostate cancer: Beyond abiraterone and enzalutamide. AB - The approval of abiraterone and enzalutamide for the treatment of advanced castration-resistant prostate cancer heralded a paradigm shift in the management of this disease. Nevertheless, new and improved treatments are needed since the disease remains incurable for the majority of these patients. In this article, we review the biology of castration-resistant disease as well as emerging therapeutic compounds directed at the androgen receptor, including galeterone, VT 464, ARN-509, and ODM-201. Mechanisms of action, early clinical data, and ongoing clinical studies for these compounds are all reviewed. The need to find optimal sequencing and combination strategies as well as the need for predictive biomarkers of response to these agents is discussed. PMID- 26162487 TI - Patterns of care for readmission after radical cystectomy in New York State and the effect of care fragmentation. AB - OBJECTIVE: To determine if readmission after radical cystectomy (RC) to the original hospital of the procedure (OrH) vs. readmission to a different hospital (DiffH) has an effect on outcomes. METHODS: The New York Statewide Planning and Research Cooperative System database was queried for discharges between January 1, 2009 and November 31, 2012 after RC in New York State. Primary outcome was mortality within 30 and 90 days. Secondary outcomes included length of stay for readmission, rate of transfers/subsequent readmissions, hospital charges per readmission, and, if applicable, length of intensive care unit stays. Multivariate linear regression analyses were performed to adjust for confounding factors in predicting mortality. RESULTS: During the study period, 2,338 patients were discharged from 100 New York State hospitals after RC. Overall rate of readmission was 28.5% and 39.7% within 30 and 90 days, respectively. Of all readmitted patients, 80.4% and 77.1% were first readmitted to OrH within 30 and 90 days, respectively. Patients readmitted to OrH were younger (P<0.0005) and had a lower All Patient Refined Severity of Illness (P = 0.004). Patients readmitted to DiffH had shorter length of stay (P<0.0005) and lower hospital charges per readmission (P<0.0005), but higher rates of transfers/subsequent readmissions (P = 0.007) and intensive care unit stays (P = 0.002) at 90 days. Patients initially readmitted to DiffH also had a higher rate of mortality (30d, 7.8% vs. 2.3%, P = 0.002; 90d, 5.2% vs. 2.5%, P = 0.05), but initial readmission status was not significant for mortality when controlling for other variables of interest. CONCLUSION: Initial readmission to DiffH vs. OrH after RC was associated with higher rates of mortality, likely owing to underlying differences in the populations. PMID- 26162488 TI - [Gallbladder agenesis. Case report]. AB - BACKGROUND: Gallbladder agenesis is a very rare congenital abnormality of the biliary tract. The diagnosis is made during surgery, because all preoperative studies have failed to identify this malformation. The purpose of this article is to present a case of gallbladder agenesis diagnosed during surgery, its management, and a review of the literature. CLINICAL CASE: The case involves a sixty-two year- old female, referring to repeated biliary colic symptoms. The abdominal ultrasound diagnosed cholelithiasis. It was impossible to identify the gallbladder during surgery. Diagnosis was confirmed by intra-operative cholangiography. DISCUSSION: Preoperative diagnostic workup has failed to recognise patients with gallbladder agenesis. It is currently recommended to abandon the surgery once this diagnosis is suspected and confirm it by a cholangio-magnetic resonance scan in order to avoid a bile duct injury. CONCLUSIONS: Agenesis of the gallbladder is a rare congenital abnormality of the biliary tree. Every surgeon must keep this rare entity in mind when a "difficult dissection" or an anatomic variant is identified during surgery, and make use of an intra-operative cholangiography, mainly to prevent a bile duct injury. PMID- 26162489 TI - [Micro RNA and its role in the pathophysiology of spinal cord injury - a further step towards neuroregenerative medicine]. AB - In the pathophysiology of spinal cord injury, the secondary biological processes involving changes in gene expression become more important day a day. Within these changes, the expression of different microRNAs has been involved in some of the pathophysiological processes of spinal cord injury. There are several studies that describe the transient expression of microRNA in spinal cord injury, some of them related to inflammation and apoptosis and others to functional recovery and regeneration. MicroRNA may be a potential target for the treatment of spinal cord injury, modifying the processes of inflammation, oxidation, apoptosis, functional recovery and regeneration. It is necessary to continue the study of microRNAs in spinal cord injury, as well as the identification of their target genes and signaling mechanisms involved in its neurological effects. With this, the ultimate goal is the development of effective and safe therapeutic and diagnostic strategies for patients with spinal cord injury. PMID- 26162490 TI - [Primary cervical cancer screening]. AB - Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis. PMID- 26162491 TI - Persistence criteria for populations with non-local dispersion. AB - In this article, we analyse the non-local model: [Formula: see text]where J is a positive continuous dispersal kernel and f(x, u) is a heterogeneous KPP type non linearity describing the growth rate of the population. The ecological niche of the population is assumed to be bounded (i.e. outside a compact set, the environment is assumed to be lethal for the population). For compactly supported dispersal kernels J, we derive an optimal persistence criteria. We prove that a positive stationary solution exists if and only if the generalised principal eigenvalue [Formula: see text] of the linear problem [Formula: see text]is negative. [Formula: see text] is a spectral quantity that we defined in the spirit of the generalised first eigenvalue of an elliptic operator. In addition, for any continuous non-negative initial data that is bounded or integrable, we establish the long time behaviour of the solution u(t, x). We also analyse the impact of the size of the support of the dispersal kernel on the persistence criteria. We exhibit situations where the dispersal strategy has "no impact" on the persistence of the species and other ones where the slowest dispersal strategy is not any more an "Ecological Stable Strategy". We also discuss persistence criteria for fat-tailed kernels. PMID- 26162492 TI - Sex-specific cutoffs for cardiac troponin using high-sensitivity assays--Is there clinical equipoise? PMID- 26162493 TI - Efficient detection of frequent eIF2B mutations for the rapid molecular diagnosis of CACH/VWM syndrome. AB - OBJECTIVES: The aim of this study was to develop a reliable, rapid and cost effective molecular diagnostic assay allowing widespread routine investigation of eIF2B-related disorders (CACH/VWM syndrome). This heterogeneous disease is caused by autosomal recessive mutations in the genes encoding the five subunits of the translation-initiation factor eIF2B. Such a diagnostic method would be particularly adapted to the apparently acute presentation of the disease. DESIGN AND METHODS: We developed a multiplex PCR amplification method for 7 genomic regions of the eIF2B genes in a single run. This method targeted the 8 most frequent mutations representing 61.4% of all mutations identified to date in our laboratory. These mutations affected eIF2B2 exon 5, eIF2B3 exon 2, eIF2B4 exons 8 and 11 and eIF2B5 exons 5, 7 and 8. PCR products were then pooled and subjected to a primer-extension assay validated using previously genotyped samples. RESULTS: The results were compared to screening and/or direct sequencing methods: 100% agreement between methods confirmed equivalent sensitivity and specificity. The new assay was highly superior in terms of cost, time to results and robustness despite sample heterogeneity. CONCLUSIONS: This genotyping strategy allows the detection of all eIF2B mutations targeted. A second multiplex primer extension assay is in development to detect the 11 next-most frequent mutations, thus raising the global detection rate to 76.8%. Our approach is widely applicable as it involves standard techniques and equipment. Moreover, it can easily be further adapted to the clinical and genetic heterogeneity of eIF2B related disorders by including or excluding mutations. PMID- 26162494 TI - Urokinase plasminogen activator receptor and its soluble form in common biopsy proven kidney diseases and in staging of diabetic nephropathy. AB - OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR), derived from membrane bound uPAR, is associated with inflammatory diseases. In the present study, we explored the expression of uPAR/suPAR in common biopsy-proven kidney diseases and the relationship between suPAR and staging of type 2 diabetic nephropathy (DN). DESIGN AND METHODS: Serum samples for suPAR and renal tissues for uPAR staining were investigated in various common kidney diseases. The levels of serum suPAR were measured and adequate cut-off values of different stage of DN were calculated by receiver operating characteristic (ROC) curve. RESULTS: In our results, the expression of uPAR on renal tissues was pronounced in the majority of kidney diseases. Comparing of expression of uPAR among different kidney diseases, it was strongest in minimal change disease (MCD) and weakest in chronic interstitial nephritis. Serum suPAR in most kidney diseases, except of MCD, was significantly elevated and was highest in DN. As for DN and suPAR, we found that suPAR progressively increased with staging of DN. Moreover, suPAR was linearly and negatively related to estimated glomerular filtration rate and positively related to the amount of proteinuria. By ROC curve, the cut-off values of suPAR in DN for assessing development increased with the progression of the disease. CONCLUSIONS: We concluded that uPAR/suPAR is elevated in most kidney diseases and that suPAR is a useful biomarker for assessing stages of DN. PMID- 26162496 TI - Lessons learned from thyroglobulin concentrations after total thyroidectomy and radioactive iodine ablation for differentiated thyroid cancer. PMID- 26162495 TI - A triple-biomarker approach for the detection of delayed graft function after kidney transplantation using serum creatinine, cystatin C, and malondialdehyde. AB - INTRODUCTION: Serum creatinine (SCr) alone does not allow for the early diagnosis of delayed graft function (DGF) following kidney transplantation (KTx). OBJECTIVE, DESIGN AND METHODS: The diagnostic utility of urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum leptin, malondialdehyde (MD.A), and cystatin C (CysC) for the early detection of DGF was previously evaluated by our group in a prospective cohort study of 40 consecutive adults undergoing KTx. Because no single biomarker achieved adequate sensitivity or specificity for practical purposes, this study was designed to evaluate the combined use of new markers with SCr. Urine and blood samples were collected 8-to-12h after KTx (day 1). Logistic regression was used to combine the biomarkers, and receiver operating characteristic curves and areas under the curve (AUC-ROC) were generated. RESULTS: Eighteen recipients developed DGF (dialysis requirement during the first post-transplant week). On day-1, the AUC for SCr to predict DGF was 0.73, 0.88 for uNGAL, 0.90 for MDA, 0.76 for leptin, and 0.91 for CysC. Adding new biomarkers to SCr enhanced the performance of DGF prediction, and the best combination was achieved with SCr, MDA, and CysC (AUC=0.96, sensitivity=100%; specificity=86%). CONCLUSION: A combination of graft damage biomarkers outperformed SCr in the early diagnosis of DGF, and the best performance was achieved by a triple-marker approach, using SCr, MDA, and CysC. PMID- 26162497 TI - Hybrid chemistry. Part 4: Discovery of etravirine-VRX-480773 hybrids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. AB - A novel series of etravirine-VRX-480773 hybrids were designed using structure guided molecular hybridization strategy and fusing the pharmacophore templates of etravirine and VRX-480773. The anti-HIV-1 activity and cytotoxicity was evaluated in MT-4 cell cultures. The most active hybrid compound in this series, N-(2 chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy)pyrimidin-2-yl)thio)acetamide 3d (EC50=0.24 , SI>1225), was more potent than delavirdine (EC50=0.66 MUM, SI>67) in the anti-HIV-1 in vitro cellular assay. Studies of structure-activity relationships established a correlation between anti-HIV activity and the substitution pattern of the acetanilide group. PMID- 26162498 TI - 4-(N-Phenyl-N'-substituted benzenesulfonyl)-6-(4-hydroxyphenyl)quinolines as inhibitors of mammalian target of rapamycin. AB - A series of 4-(N-phenyl-N'-substituted benzenesulfonyl)-6-(4 hydroxyphenyl)quinolines was designed, synthesized and evaluated for their biological potential as anticancer agents by screening the molecules against panel of five human cancer cell lines viz. HL-60, MiaPaCa-2, HCT116, PC-3 and HEP G2. The series has shown good mTOR inhibitory activity at 0.5 MUM concentration. The representative compound 7h was found to be most active with the IC50 of 613 nM against mTOR. In supportive evidence, the western blotting experiment revealed that compound 7h is more potent in inhibiting p-mTOR (S2448) activity in 2-4h at 5 and 10 MUM concentrations and was selective and specific towards mTORC1 versus mTORC2. Towards understanding the mechanistic aspects we studied cell cycle analysis, mitochondrial membrane potential loss in MiaPaca-2 cells for compound 7h. The docking study for this series was performed to understand the binding mode of the compounds and its consequent effect in biological activity, the initial interaction studies were found to be useful in design of molecules, where compound 7h has shown additional H-bond interaction with Lys2171 apart from Val2240 and also a small hydrophobic cleft was observed with Leu2185, Met2345 and Ile2356. PMID- 26162499 TI - Childhood Obesity related Co-morbidities and Retinol Binding Protein 4: An Evolving Understanding. PMID- 26162500 TI - Tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine for photodynamic cancer therapy. AB - Photodynamic therapy (PDT) has emerged as an effective and minimally invasive treatment option for several diseases, including some forms of cancer. However, several drawbacks of the approved photosensitizers (PS), such as insufficient light absorption at therapeutically relevant wavelengths hampered the clinical effectiveness of PDT. Phthalocyanines (Pc) are interesting PS-candidates with a strong light absorption in the favourable red spectral region and a high quantum yield of cancer cell destroying singlet oxygen generation. Here, we evaluated the suitability of tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as novel PS for PDT. ZnPc-induced phototoxicity, induction of apoptosis as well as cell cycle arresting effects was studied in the human gastrointestinal cancer cell lines of different origin. Photoactivation of ZnPc-pretreated (1-10 MUM) cancer cells was achieved by illumination with a broad band white light source (400-700 nm) at a power density of 10 J/cm(2). Photoactivation of ZnPc loaded cells revealed strong phototoxic effects, leading to a dose-dependent decrease of cancer cell proliferation of up to almost 100%, the induction of apoptosis and a G1-phase arrest of the cell cycle, which was associated with decrease in cyclin D1 expression. By contrast, ZnPc-treatment without illumination did not induce any cytotoxicity, apoptosis, cell cycle arrest or decreased cell growth. Antiangiogenic effects of ZnPc-PDT were investigated in vivo by performing CAM assays, which revealed a marked degradation of blood vessels and the capillary plexus of the chorioallantoic membrane of fertilized chicken eggs. Based on our data we think that ZnPc may be a promising novel photosensitizer for innovative PDT. PMID- 26162501 TI - Inhibitory and immunological effects induced by the combination of photodynamic therapy and dendritic cells on mouse transplanted hepatoma. AB - OBJECTIVE: To investigate the anti-tumor and immune efficacy of photodynamic immune-therapy (PIT), the combination of photodynamic therapy and dendritic cells (DC), on murine Heps hepatoma. METHODS: DCs were derived from syngeneic mouse bone marrow and then labeled with DAPI in vitro. The hepatoma model was established by subcutaneous inoculation with Heps cells in one hundred and twenty eight mice. They were then divided into four groups at random: control group, PDT group, DC group and PIT group. Tumors in the control group were injected with normal saline. Mice in the PDT group were injected with the photosensitizer Deuteporfin 24 h before irradiation. Mice in the DC group were injected with DAPI labeled dendritic cells intratumorally. Mice in the PIT group were further given an injection of DCs after photoirradiation. Tumor growth and survival time were recorded after treatment. Fluorescence of tumor draining lymph nodes was evaluated under fluorescence microscope. Cytotoxic activity of splenocytes was tested by standard lactate dehydrogenase (lactate dehydrogenase, LDH) release assay. RESULTS: (1) Tumor growth was significantly slowed down in the PDT and PIT group compared to the control group (P<0.01). (2) The mean survival time was significantly prolonged in the PDT and PIT group. (3) The number of fluorescent cells in the draining lymph nodes from DC group was higher than that of the PIT group. (4) The anti-tumor activity of splenocytes in the PDT and PIT group was significantly higher than that of the DC and control groups (P<0.01, P<0.01). CONCLUSIONS: The present study suggests that PDT can inhibit tumor growth and induce anti-tumour immune response. The combination of PDT induced by Deuteporfiin and dendritic cell is capable of amplifying the antitumor immune response. PMID- 26162502 TI - How eukaryotic filamentous pathogens evade plant recognition. AB - Plant pathogenic fungi and oomycetes employ sophisticated mechanisms for evading host recognition. After host penetration, many fungi and oomycetes establish a biotrophic interaction. It is assumed that different strategies employed by these pathogens to avoid triggering host defence responses, including establishment of biotrophic interfacial layers between the pathogen and host, masking of invading hyphae and active suppression of host defence mechanisms, are essential for a biotrophic parasitic lifestyle. During the infection process, filamentous plant pathogens secrete various effectors, which are hypothesized to be involved in facilitating effective host infection. Live-cell imaging of fungi and oomycetes secreting fluorescently labeled effector proteins as well as functional characterization of the components of biotrophic interfaces have led to the recent progress in understanding how eukaryotic filamentous pathogens evade plant recognition. PMID- 26162503 TI - Influence of morphological parameters on the development of gingival recession in class III malocclusion. AB - Cephalometric analysis, including both basic cranio- and gnathometric measurements and detailed evaluation of the construction of skeletal, muscular and mucosal systems combined with estimation of the risk of recession's occurrence, can be used to determine the direction of therapy and ensure appropriate aesthetic-functional effects of treatment. The objective of the present study was to compare the influence of the chosen morphologic parameters on the development of gingival recession in the front part of the jaw in patients with Angle class III. The research material was based on the medical documentation of 1800 patients. Sixty generally healthy patients qualified for the research with prognathism. On the basis of the side-head cephalograms, measurements were carried out to describe the bone structure in the front section of the lower jaw. The lower incisor teeth set-up was also analyzed. Gum recession of the lower incisor teeth was assessed on the basis of the inside-mouth photos of the patients with class III malocclusion. The occurrence of recession in a further 4 patients resulted from such a positioning of the lower teeth. In patients in the first group, treated with complex ortho-surgical treatment, the lower incisor teeth were adjusted much more vertically in the alveola and, thus, recession occurred only in one patient. Complex orthodontic-surgical therapy contributes to recession development to a lesser degree than the sham treatment and makes it a safe alternative therapy in patients with high diathesis for occurrence or progression of an existing recession. PMID- 26162504 TI - Synthesis of Enantiopure 3-Hydroxypiperidines from Sulfinyl Dienyl Amines by Diastereoselective Intramolecular Cyclization and [2,3]-Sigmatropic Rearrangement. AB - The highly diastereoselective base-promoted intramolecular cyclization of a variety of enantiopure sulfinyl dienyl amines provides novel sulfinyl tetrahydropyridines that are readily converted to 3-hydroxy tetrahydropyridines via sigmatropic rearrangement. The influence of N- and C- substituents on the process has been studied. Procedures to shorten the sequence such as the tandem cyclization followed by [2,3]-sigmatropic rearrangement, as well as cyclization of the free amine, under Boc- or ArSO- deprotection conditions have been examined. Good to excellent levels of selectivity are generally observed for the reported transformations (dr: 75/25 to >98/2). A novel protocol to access substituted amino dienyl sulfoxides is also reported. PMID- 26162505 TI - Telomerase lost? AB - Telomerase and telomerase-generated telomeric DNA sequences are widespread throughout eukaryotes, yet they are not universal. Neither telomerase nor the simple DNA repeats associated with telomerase have been found in some plant and animal species. Telomerase was likely lost from Diptera before the divergence of Diptera and Siphonaptera, some 260 million years ago. Even so, Diptera is one of the most successful animal orders, making up 11% of known animal species. In addition, many species of Coleoptera and Hemiptera seem to lack canonical telomeric repeats at their chromosome ends. These and other insects that appear to lack canonical terminal repeat sequences account for another 10-15% of animal species. Conversely, the silk moth Bombyx mori maintains canonical telomeric sequences at its chromosome ends but seems to lack a functional telomerase. We speculate that a telomere-specific capping complex that recognizes the telomeric repeats and protects chromosome ends is the determining factor in maintaining canonical telomeric sequences and that telomerase is an early and efficacious mechanism for satisfying the needs of capping complex. There are alternate mechanisms for maintaining chromosome ends that do not depend on telomerase, such as recombination found in some human cancer cells and yeast mutants. These mechanisms may maintain the canonical telomeric repeats or allow the terminal sequence to evolve when specificity of the capping complex for terminal repeat sequences is weak. PMID- 26162506 TI - Enhancing Communication Related to Symptom Management Through Plain Language. AB - CONTEXT: Symptom management is a key dimension of palliative care. In addition to aspects such as assessment and pharmacological management of symptoms, professionals also require communication skills to effectively manage symptoms in serious illness. OBJECTIVES: Application of the Plain Language Planner for Palliative Care((c)), a provider tool for communicating about medication and symptoms using plain language, was tested. METHODS: Approximately 75% of the 155 health care professionals, mostly nurses, who participated in a before-and-after educational activity about the tool, provided written communication explanations using one of three medication-symptom pairs: senna for constipation, amitriptyline for nerve pain, and lorazepam for anxiety. Responses were coded for plain language characteristics: active voice, second person, use of jargon, brief sentences, reading level, and easy to understand data phrasing. Frequency counts for coding categories were calculated and compared across medication-symptom pairs before and after the education session. RESULTS: A comparison between written responses before and after the education session showed improvement in the use of plain language. Overall, plain language scores were highest for communication about senna (81%), followed by amitriptyline (72%) and lorazepam (77%). Across all three medication-symptom pairs, the greatest improvement in the use of plain language occurred in the use of jargon. CONCLUSION: Provider training with the tool produced increased plain language. Use of the tool in provider education shows promise in increasing the health literacy for patients and families regarding symptom management. PMID- 26162507 TI - Determinants of Hospital Death for Taiwanese Pediatric Cancer Decedents, 2001 2010. AB - CONTEXT: Factors influencing pediatric cancer patients' place of death may have evolved with advances in medical and hospice care since earlier studies were done. OBJECTIVES: To comprehensively analyze factors associated with hospital death in an unbiased population of pediatric cancer patients in Taiwan. METHODS: This was a retrospective cohort study using administrative data for 1603 Taiwanese pediatric cancer patients who died in 2001-2010. Place of death was hypothesized to be associated with 1) patient sociodemographics and disease characteristics, 2) primary physician's specialty, 3) characteristics and health care resources at both the hospital and regional levels, and 4) historical trends. RESULTS: Most Taiwanese pediatric cancer patients (87.4%) died in an acute care hospital. The probability of dying in hospital increased slightly over time, reaching significance only in 2009 (adjusted odds ratio [AOR], 95% CI: 2.84 [1.32-6.11]). Children were more likely to die in an acute care hospital if they resided in the most urbanized area, were diagnosed with leukemia or lymphoma (2.32 [1.39-3.87]), and received care from a pediatrician (1.58 [1.01-2.47]) in a nonprofit proprietary hospital (1.50 [1.01-2.24]) or large hospital, reaching significance for the third quartile (2.57 [1.28-5.18]) of acute care hospital beds. CONCLUSION: Taiwanese pediatric cancer patients predominantly died in an acute care hospital with a slightly increasing trend of shifting place of death from home to hospital. Propensity for hospital death was determined by residential urbanization level, diagnosis, primary physician's specialty, and the primary hospital's characteristics and health care resources. Clinical interventions and health policies should ensure that resources are allocated to allow pediatric cancer patients to die in the place they and their parents prefer to achieve a good death and promote their parents' bereavement adjustment. PMID- 26162508 TI - Timing of POLST Form Completion by Cause of Death. AB - CONTEXT: The physician orders for life-sustaining treatment (POLST) paradigm allows health care professionals to document the treatment preferences of patients with advanced illness or frailty as portable and actionable medical orders. National standards encourage offering POLST orders to patients for whom clinicians would not be surprised if they died in the next year. OBJECTIVES: To determine the influence of cause of death on the timing of POLST form completion and on changes to POLST orders as death approaches. METHODS: This was a cohort study of 18,285 Oregon POLST Registry decedents who died in 2010-2011 matched to Oregon death certificates. RESULTS: The median interval between POLST completion and death was 6.4 weeks. Those dying of cancer had forms completed nearer death (median 5.1 weeks) than those with organ failure (10.6 weeks) or dementia (14.5 weeks; P < 0.001). More than 90% of final POLST forms indicated orders for no resuscitation and 65.1% listed orders for comfort measures only. Eleven percent of the sample had multiple registered forms during the two years preceding their death, with the form completed nearest to death more likely than earlier forms to have orders for no resuscitation and comfort measures only, although some later forms did have orders for more treatment. CONCLUSION: More than half of POLST forms were completed in the final two months of life. Cause of death influenced when POLST forms were completed. POLST forms changed in the two years preceding death, more frequently recording fewer life-sustaining treatment orders than the earlier form(s). PMID- 26162509 TI - High Expression of p62 Protein Is Associated with Poor Prognosis and Aggressive Phenotypes in Endometrial Cancer. AB - High expression of SQSTM1/p62 (p62) protein, which functions as a hub of oncogenic signaling pathways, has been detected in several human cancers. However, the clinicopathological and functional contribution of p62 expression is largely unknown in endometrial cancers (ECs). In this study, we assessed the expression status of p62 in primary ECs (n = 194) by immunohistochemistry and analyzed its clinical significance. Although p62 was expressed in the cytoplasm and/or nucleus in primary ECs, we observed that an expression subtype, high expression of cytoplasmic p62 but low expression of nuclear p62 (cytoplasm(High)/nucleus(Low)), significantly correlated with nonendometrioid types (P = 0.002), high grade (P < 0.001), deep myometrial invasion (P = 0.025), vascular invasion (P = 0.012), and poor prognosis (P < 0.001), and may be an independent prognostic marker of ECs (P = 0.011). Furthermore, RNA interference mediated inhibition of p62 expression in the HEC-1A EC cell line led to the reduction of invasiveness and resistance to oxidative stress in vitro, as well as the suppression of in vivo tumor growth in an orthotopic mouse model of ECs. High expression of cytoplasmic p62 is a novel prognostic biomarker of ECs, and excess p62 expression may functionally contribute to the acquirement of malignant phenotypes in EC cells. PMID- 26162510 TI - Guidance for improving comparability and relevance of oil toxicity tests. AB - The complex nature and limited aqueous solubility of petroleum substances pose challenges for consistently characterizing exposures in aquatic life hazard assessments. This paper reviews important considerations for the design, conduct and interpretation of laboratory toxicity tests with physically and chemically dispersed oils based on an understanding of the behavior and toxicity of the hydrocarbons that comprise these substances. Guiding principles are provided that emphasize the critical need to understand and, when possible, characterize dissolved hydrocarbon exposures that dictate observed toxicity in these tests. These principles provide a consistent framework for interpreting toxicity studies performed using different substances and test methods by allowing varying dissolved exposures to be expressed in terms of a common metric based on toxic units (TUs). The use of passive sampling methods is also advocated since such analyses provide an analytical surrogate for TUs. The proposed guidance is translated into a series of questions that can be used in evaluating existing data and in guiding design of future studies. Application of these questions to a number of recent publications indicates such considerations are often ignored, thus perpetuating the difficulty of interpreting and comparing results between studies and limiting data use in objective hazard assessment. Greater attention to these principles will increase the comparability and utility of oil toxicity data in decision-making. PMID- 26162511 TI - Development of waterborne oil spill sensor based on printed ITO nanocrystals. AB - Oil spill accidents occasionally occur in coastal and ocean environments, and cause critical environmental damage, spoiling the marine habitats and ecosystems. To mitigate the damages, the species and amount of spilled oil should be monitored. In this study, we developed a waterborne oil spill sensor using a printed ITO layer. ITO is a compatible material for salty environments such as oceans because ITO is strong against corrosion. The fabricated sensor was tested using three oils, gasoline, lubricant and diesel, and different oil thicknesses of 0, 5, 10, and 15mm. The results showed that the resistance of the sensor clearly increased with the oil thickness and its electrical resistance. For sustainable sensing applications in marine environments, XRD patterns confirmed that the crystal structure of the ITO sensor did not change and FE-SEM images showed that the surface was clearly maintained after tests. PMID- 26162512 TI - Tongue sole (Cynoglossus semilaevis) prothymosin alpha: Cytokine-like activities associated with the intact protein and the C-terminal region that lead to antiviral immunity via Myd88-dependent and -independent pathways respectively. AB - Prothymosin alpha (ProTalpha) is a small protein that in mammals is known to participate in diverse biological processes including immunomodulation. In teleost, the immunological function of ProTalpha is unknown. In the current study, we investigated the expression and function of the ProTalpha (named CsProTalpha) from the teleost fish tongue sole (Cynoglossus semilaevis). We found that CsProTalpha expression was abundant in immune relevant tissues and upregulated by megalocytivirus infection. Immunoblot detected secretion of CsProTalpha by peripheral blood leukocytes. Recombinant CsProTalpha (rCsProTalpha) as well as the C-terminal 11-residue (Ct11) were able to bind head kidney monocytes (HKM) and induce immune gene expression; however, the induction patterns caused by rCsProTalpha and Ct11 differed considerably. When introduced in vivo, rCsProTalpha and Ct11 significantly reduced megalocytivirus infection in fish tissues, whereas rCsProTalpha antibody significantly promoted viral replication. Blocking of Myd88 activity abolished the virus-inhibitory effect of rCsProTalpha but not Ct11. Taken together, these results demonstrate for the first time that both the intact protein and the C-terminal segment of a teleost ProTalpha can act like cytokines and induce antiviral immunity via, however, distinct signaling pathways that differ in the requirement of Myd88. PMID- 26162513 TI - Elution of High Dose Amphotericin B Deoxycholate From Polymethylmethacrylate. AB - Fungal periprosthetic joint infections are rare, devastating complications of arthroplasty. There is conflicting evidence as to the efficacy of amphotericin B elution from cement spacers. The purpose of this study was to determine whether concentrations of amphotericin B released from bone cement over time would be efficacious in treating a periprosthetic infection. A continuous flow chamber was used to evaluate the in vitro release of amphotericin from cement beads containing 7.5% amphotericin. Following polymerization, 3.3% of the initially loaded amphotericin B was detected. The peak mean concentration eluted from the bone cement was 0.33 MUg/mL at 8 hours. The AUC0-24 was 2.79 MUg/mL/h; 0.20% of the amphotericin B was released. In conclusion, amphotericin B is released from bone cement at a clinically useful concentration. PMID- 26162514 TI - Absence of a Tourniquet Does Not Affect Fixation of Cemented TKA: A Randomized RSA Study of 70 Patients. AB - We aimed to determine whether not using a tourniquet in cemented TKA would affect migration of the tibial component measured by radiosterometric analysis (RSA). Seventy patients were randomized into a tourniquet group and a non-tourniquet group and using model-based RSA, the migration of the tibial component was analyzed. Primary and secondary outcome measures were maximum total point motion (MTPM) and translations and rotations. Follow-up period was 2 years. The tibial component was well fixated in both groups and no significant difference in migration between the two groups was detected (P=0.632). Mean MTPM (SD) was 0.47 mm (0.16) in the tourniquet group and 0.45 mm (0.21) in the non-tourniquet group. Absence of tourniquet indicates that stable fixation of the tibial component can be achieved in cemented TKA. PMID- 26162515 TI - Lipidomic analysis of plasma lipoprotein fractions in myocardial infarction-prone rabbits. AB - Lipids play important roles in the body and are transported to various tissues via lipoproteins. It is commonly assumed that alteration of lipid levels in lipoproteins leads to dyslipidemia and serious diseases such as coronary artery disease (CAD). However, lipid compositions in each lipoprotein fraction induced by lipoprotein metabolism are poorly understood. Lipidomics, which involves the comprehensive and quantitative analysis of lipids, is expected to provide valuable information regarding the pathogenic mechanism of CAD. Here, we performed a lipidomic analysis of plasma and its lipoprotein fractions in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. In total, 172 lipids in plasma obtained from normal and WHHLMI rabbits were quantified with high throughput and accuracy using supercritical fluid chromatography hybrid quadrupole-Orbitrap mass spectrometry (SFC/Q-Orbitrap-MS). Plasma levels of each lipid class (i.e., phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, ceramide, triacylglycerol, diacylglycerol, and cholesterol ester, except for free fatty acids) in 21-month old WHHLMI rabbits were significantly higher than those in normal rabbits. High levels of functional lipids, such as alkyl-phosphatidylcholines, phospholipids including omega-6 fatty acids, and plasmalogens, were also observed in WHHLMI rabbit plasma. In addition, high-resolution lipidomic analysis using very low density lipoprotein (VLDL) and low density lipoprotein (LDL) provided information on the specific molecular species of lipids in each lipoprotein fraction. In particular, higher levels of phosphatidylethanolamine plasmalogens were detected in LDL than in VLDL. Our lipidomics approach for plasma lipoprotein fractions will be useful for in-depth studies on the pathogenesis of CAD. PMID- 26162516 TI - Optimization of Dual-Labeled Antibodies for Targeted Intraoperative Imaging of Tumors. AB - For intraoperative imaging, antibodies labeled with both a radionuclide and a fluorophore may be used to tag the tumor lesion with a radiolabel and a fluorescent signal at high tumor to background ratios. However, labeling antibodies with fluorescent moieties may affect the in vivo behavior of the antibody depending on the dye to antibody substitution ratio. To investigate the optimal substitution ratio for use in dual-modality image-guided surgery, we conjugated three different antibodies, MN-14 (anti-CEACAM5), girentuximab (anti CAIX), and cetuximab (anti-EGFR), with both diethylene triamine pentaacetic acid (DTPA, for labeling with 111In) and IRdye 800CW at dye to antibody ratios of 0, 1, 1.5, 2, and 3 and assessed in vivo behavior. Biodistribution studies showed that at high dye to antibody ratios, liver uptake of the dual-labeled antibodies increased, whereas tumor uptake decreased. Conversely, very low ratios may not be optimal either because in that case, only a few antibody molecules will be dual labeled (i.e., contain both a DTPA and an IRDye 800CW moiety), which may complicate interpretation of dual-modality data. The present study shows that, provided that the chelator to antibody ratio is high enough, a dye to antibody ratio in the range of 1 to 1.5 is optimal for antibody-targeted dual-modality imaging applications. However, the optimal configuration is antibody dependent and should be determined for each dual-labeled antibody individually. PMID- 26162517 TI - Analytical modeling of drug dynamics induced by eluting stents in the coronary multi-layered curved domain. AB - Pharmacokinetics induced by drug eluting stents (DES) in coronary walls is modeled by means of a one-dimensional multi-layered model, accounting for vessel curvature and non-homogeneous properties of the arterial tissues. The model includes diffusion mechanisms, advection effects related to plasma filtration through the walls, and bio-chemical drug reactions. A non-classical Sturm Liouville problem with discontinuous coefficients is derived, whose closed-form analytical solution is obtained via an eigenfunction expansion. Soundness and consistency of the proposed approach are shown by numerical computations based on possible clinical treatments involving both hydrophilic and hydrophobic drugs. The influence of the main model parameters on drug delivery mechanisms is analyzed, highlighting the effects induced by vessel curvature and yielding comparative indications and useful insights into the concurring mechanisms governing the pharmacokinetics. PMID- 26162518 TI - Ceftazidime-avibactam activity when tested against ceftazidime-nonsusceptible Citrobacter spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa from Unites States medical centers (2011-2014). AB - A total of 6910 Enterobacteriaceae with inducible AmpC beta-lactamases and 5328 Pseudomonas aeruginosa were collected from 71 US hospitals in 2011-2014 and were susceptibility tested using the reference broth microdilution method. Ceftazidime avibactam demonstrated potent in vitro activity against all 3 Enterobacteriaceae genus groups evaluated, with MIC(50)/MIC(90) values of 0.12/0.5 MUg/mL for Enterobacter spp. and Serratia marcescens and 0.12/0.25 MUg/mL for Citrobacter spp. (99.8-99.9% susceptibility rates at <=8 MUg/mL). Furthermore, 99.3% of ceftazidime-nonsusceptible Enterobacteriaceae isolates (1015 of 1022) were susceptible to ceftazidime-avibactam (MIC(50)/MIC(90) of 0.25-0.5/1-2 MUg/mL), whereas susceptibility rates for cefepime ranged from 45.9% (Citrobacter spp.) to 80.0% (S. marcescens). Ceftazidime-avibactam was also very active against P. aeruginosa (MIC(50)/MIC(90), 2/4 MUg/mL; 96.8% inhibited at <=8 MUg/mL). P. aeruginosa susceptibility rates to other antipseudomonal beta-lactams ranged from 79.6% for piperacillin-tazobactam to 84.5% for cefepime. Ceftazidime-avibactam inhibited 67.4% of isolates at <=8 MUg/mL (MIC(50)/MIC(90), 8/32 MUg/mL) that were nonsusceptible to ceftazidime, cefepime, piperacillin-tazobactam, and meropenem. PMID- 26162519 TI - Synthesis, in vitro evaluation and molecular docking studies of thiazole derivatives as new inhibitors of alpha-glucosidase. AB - A series of thiazole derivatives 1-21 were prepared, characterized by EI-MS and (1)H NMR and evaluated for alpha-glucosidase inhibitory potential. All twenty one derivatives showed good alpha-glucosidase inhibitory activity with IC50 value ranging between 18.23+/-0.03 and 424.41+/-0.94MUM when compared with the standard acarbose (IC50, 38.25+/-0.12MUM). Compound (8) (IC50, 18.23+/-0.03MUM) and compound (7) (IC50=36.75+/-0.05MUM) exhibited outstanding inhibitory potential much better than the standard acarbose (IC50, 38.25+/-0.12MUM). All other analogs also showed good to moderate enzyme inhibition. Molecular docking studies were carried out in order to find the binding affinity of thiazole derivatives with enzyme. Studies showed these thiazole analogs as a new class of alpha-glucosidase inhibitors. PMID- 26162520 TI - PEGylation of Polypropylenimine Dendrimer with Alkylcarboxylate Chain Linkage to Improve DNA Delivery and Cytotoxicity. AB - One of the major limitations of effective nonviral gene carriers is their potential high cytotoxicity. Conjugation of polyethylene glycol (PEG) to polymers is a common approach to decrease toxicity and improve biodistribution. The aim of this study was to evaluate the effect of PEGylation on generation 5 polypropylenimine (PPI) dendrimer by using PEG moieties or alkyl-PEG groups. Polymers were synthesized by grafting of 5 and 10 % primary amines of PPI to NH2 PEG-COOH or Br-(CH2)9-CO-NH-PEG-COOH through Amide bond formation or nucleophilic substitution, respectively. Transfection efficiency and cytotoxicity were analyzed after 4 and 24 h exposure of neuroblastoma cell line (Neuro-2a) with synthesized vectors. Among all of the PEG-PPI derivatives, 5 % PEG-conjugated G5 PPI with alkyl chain (PPI-alkyl-PEG 5 %) resulted in the most efficient gene expression. This vector also significantly decreased the in vitro cytotoxicity and sub-G1 peak in flow cytometry histogram after 24 h incubation. Our results indicate that modification of 5 % primary amines of G5 PPI with PEG using alkyl chain as linker produces a promising vector combining low cytotoxicity, appropriate biodegradability, and high gene transfection efficiency. PMID- 26162521 TI - Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study. AB - PURPOSE: Testosterone (T) exerts different effects on the cardiovascular system. Despite this knowledge, the acute vascular effect of androgen remains still poorly understood. METHODS: We investigated the acute effects of T on vascular function in ten men (18-40 years age) with hypogonadism and severe hypotestosteronemia [serum total testosterone (TT) = 0.6 +/- 0.3 ng/mL]. In a 4 day double-blind, randomized, placebo-controlled crossover study, we administered 80 mg daily dose of transdermal-T gel (TG) and evaluated endothelial variations with Endopat2000 (reactive hyperemia index, RHI and the augmentation index, AI); also, CAG repeat polymorphism in exon 1 of the androgen receptor gene was investigated. RESULTS: After TG administration, RHI significantly improved at 4 h (p < 0.05), while AI improvement was recorded at 4 and 96 h, also when adjusted for heart rate (AI@75; p < 0.01 and p < 0.001, respectively). Direct relationships between DeltaT, DeltaDHT and DeltaRHI variations (r = 0.37, p < 0.01; r = 0.17, p < 0.05, respectively) as well as between "CAG repeats" length and DeltaLnRHI at 96 h (p < 0.03, r (2) = 0.47) were found. An inverse relationship between DeltaT and DeltaAI (p < 0.01, r = -0.35) and DeltaAI@75 (p < 0.01, r = -0.38) were found. CONCLUSION: Administration of TG causes an acute vasodilation and improves arterial stiffness probably due to non-genomic actions of T. Endothelial vasodilatory response was more pronounced depending on higher plasma TT and DHT levels attained. Clinical implications in elderly frail populations are discussed. PMID- 26162522 TI - ENDOCRINOLOGY AND ART. The acromegalic voice of Tango: Don Edmundo Rivero. PMID- 26162524 TI - Thermal and catalytic slow pyrolysis of Calophyllum inophyllum fruit shell. AB - Pyrolysis of Calophyllum inophyllum shell was performed in a fixed bed pyrolyser to produce pyrolytic oil. Both thermal (without catalysts) and catalytic pyrolysis process were conducted to investigate the effect of catalysts on pyrolysis yield and pyrolysis oil characteristics. The yield of pyrolytic oil through thermal pyrolysis was maximum (41% wt) at 425 degrees C for particle size of 1.18 mm and heating rate of 40 degrees C/min. In catalytic pyrolysis the pyrolytic oil yield was maximum (45% wt) with both zeolite and kaolin catalysts followed by Al2O3 catalyst (44% wt). The functional groups and chemical components present in the pyrolytic oil are identified by Fourier Transform Infrared Spectroscopy (FT-IR) and Gas Chromatography-Mass Spectrometry (GC-MS) techniques. This study found that C. inophyllum shell is a potential new green energy source and that the catalytic pyrolysis process using zeolite catalyst improves the calorific value and acidity of the pyrolytic oil. PMID- 26162523 TI - Start-up of a spiral periphyton bioreactor (SPR) for removal of COD and the characteristics of the associated microbial community. AB - Periphyton-based bioreactors are widely accepted for removing various pollutants from wastewater; however, the slow start-up and low efficiency in widely fluctuating temperatures limit its application. A spiral periphyton bioreactor (SPR) was developed and its COD removal capability and the associated microbial communities were investigated. This SPR can be easily backwashed to stimulate periphyton growth and efficiently remove COD at temperatures ranging from 4 to 30 degrees C. The species richness and evenness of the periphyton community increased during domestication, while its functional diversity and organic carbon metabolic vitality were higher after 30 days domestication. Cyanobacteria were the main components of the SPR and produced an aerobic environment, while Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and Sphingobacteria were the microorganisms responsible for COD removal. This study provides valuable insights into changes in pivotal microorganisms of the periphyton community during domestication, and indicates that SPR is simple to operate and efficient in COD removal. PMID- 26162525 TI - Cultivation of Nannochloropsis for eicosapentaenoic acid production in wastewaters of pulp and paper industry. AB - The eicosapentaenoic acid (EPA) containing marine microalga Nannochloropsis oculata was grown in an effluent from anaerobic digestion of excess activated sludge from a wastewater treatment plant serving a combination of a pulp and a paper mill and a municipality (digester effluent, DE), mixed with the effluent of the same wastewater treatment plant. The maximum specific growth rate and photosynthesis of N. oculata were similar in the DE medium and in artificial sea water medium (ASW) but after 7 days, algae grown in the DE medium contained seven times more triacylglycerols (TAGs) per cell than cells grown in ASW, indicating mild stress in the DE medium. However, the volumetric rate of EPA production was similar in the ASW and DE media. The results suggest that N. oculata could be used to produce EPA, utilizing the nutrients available after anaerobic digestion of excess activated sludge of a pulp and paper mill. PMID- 26162526 TI - Characterization of a multi-metal binding biosorbent: Chemical modification and desorption studies. AB - This work attends to preparation and characterization of a novel multi-metal binding biosorbent after chemical modification and desorption studies. Biomass is a combination of tea waste, maple leaves and mandarin peels with a certain proportion to adsorb cadmium, copper, lead and zinc ions from aqueous solutions. The mechanism involved in metal removal was investigated by SEM, SEM/EDS and FTIR. SEM/EDS showed the presence of different chemicals and adsorbed heavy metal ions on the surface of biosorbent. FTIR of both unmodified and modified biosorbents revealed the important role of carboxylate groups in heavy metal biosorption. Desorption using different eluents and 0.1 M HCl showed the best desorption performance. The effectiveness of regeneration step by 1 M CaCl2 on five successive cycles of sorption and desorption displays this multi-metal binding biosorbent (MMBB) can effectively be utilized as an adsorbent to remove heavy metal ions from aqueous solutions in five cycles of sorption/desorption/regeneration. PMID- 26162527 TI - Characterization of Luminance and Color Properties of 6-MP Wide-Screen Displays. AB - Luminance and color performance are routinely evaluated as part of acceptance testing of displays used in diagnostic radiology. Previous work has indicated that as some diagnostic liquid crystal displays (LCDs) increase in backlight hours (BLH), the luminance measured with an external luminance meter exceeds the luminance reported by the manufacturer's built-in meter. The purposes of this work were as follows: first, to characterize several luminance and color performance characteristics for 23 Barco Coronis Fusion 6-MP MDCC 6230 color displays and, second, to provide initial data for a longitudinal study evaluating changes in luminance and color performance as BLH increase. Grayscale display conformance and maximum luminance were evaluated using a calibrated luminance meter and AAPM Task Group 18 test patterns, and agreement between target and measured luminance was calculated. Luminance uniformity was evaluated by calculating maximum luminance deviation. Color point and color uniformity were evaluated using a spectrophotometer, and the radial color distances between the corners and center of the display were calculated. Above 3 cd/m(2), there was good agreement between the target and measured luminance. At the maximum luminance, the mean difference was less than 1 %. The mean maximum luminance deviation for these displays was 10.40 +/- 2.38 %. Color point was observed to be very consistent between displays with mean values of u' and v' of 0.187 +/- 0.002 and 0.474 +/- 0.004, respectively. Among all displays, maximum radial color distance had a mean value of 0.003 +/- 0.001. These data provide a baseline for the acceptance of future displays as well as for longitudinal studies of luminance and color performance. PMID- 26162528 TI - Flocculation of copper(II) and tetracycline from water using a novel pH- and temperature-responsive flocculants. AB - Insufficient research is available on flocculation of combined pollutants of heavy metals and antibiotics, which widely exist in livestock wastewaters. Aiming at solving difficulties in flocculation of this sort of combined pollution, a novel pH- and temperature-responsive biomass-based flocculant, carboxymethyl chitosan-graft-poly(N-isoproyl acrylamide-co-diallyl dimethyl ammonium chloride) (denoted as CND) with two responsive switches [lower critical solution temperature (LCST) and isoelectric point (IEP)], was designed and synthesized. Its flocculation performance at different temperatures and pHs was evaluated using copper(II) and tetracycline (TC) as model contaminants. CND exhibited high efficiency for coremoval of both contaminants, whereas two commercial flocculants (polyaluminum chloride and polyacrylamide) did not. Especially, flocculation performance of the dual-responsive flocculant under conditions of temperature>LCST and IEP(contaminants)=2 bone pain and any grade bone pain in the first chemotherapy cycle and across cycles 1-6. RESULTS: Of the 1949 patients analyzed, 19 and 36 % had grade >=2 and any grade bone pain, respectively, in cycle 1, and 28 and 51 % had grade >=2 and any grade bone pain, respectively, across cycles 1 6. In cycle 1, history of bone pain (odds ratio (OR), 1.51; 95 % confidence interval (CI), 1.09-2.07) was associated with increased risk of grade >=2 bone pain; age >=65 years (versus <45 years; OR, 0.64; 95 % CI, 0.42-0.98), the European Union region (versus the USA region; OR, 0.32; 95 % CI, 0.20-0.52), colorectal cancer (versus breast cancer; OR, 0.14; 95 % CI, 0.05-0.41), and small cell lung cancer (OR, 0.34; 95 % CI, 0.12-0.98) were associated with reduced risk of grade >=2 bone pain. CONCLUSIONS: Potential risk factors for bone pain in patients receiving myelosuppressive chemotherapy and primary prophylactic pegfilgrastim identified in this study are younger age and history of bone pain. No other association with clinical factors and risk of bone pain was detected. Better understanding of risk factors for bone pain would be useful in identifying patients who may benefit from pain prevention strategies. PMID- 26162537 TI - Routine prescribing of gabapentin or pregabalin in supportive and palliative care: what are the comparative performances of the medications in a palliative care population? AB - Neuropathic pain is a prevalent and distressing problem faced by people with life limiting illness that is often difficult to palliate. Gabapentin and pregabalin are widely prescribed as part of the routine approach to palliating neuropathic pain. Although they are often viewed as interchangeable agents, very little comparative data of their benefits and harms exists in clinical practice. Two previously reported pharmacovigilance studies that had used the same methodology for gabapentin and pregabalin were compared. These studies examined the benefits and harms of gabapentin and pregabalin after the medications had been routinely prescribed by clinicians working in a network of palliative care services using the same data collection tools with the same definitions and the same time points. Data were collected over 21 days from 282 patients prescribed either gabapentin or pregabalin for pain. Items included medication doses, pain scores, and adverse effects. In order to compare the medication responses, the final doses of pregabalin were converted to gabapentin does equivalents using previously published recommendations. The final pain scores were similar for both groups, and the reduction in pain were similar (OR = 11.2; 95 % CI 3.9, 32.7, p < 0.001). However, this was achieved at lower doses of gabapentin compared to pregabalin. Those receiving gabapentin were more likely to experience harms (OR = 3.5; 95 % CI 1.4, 9.1, p = 0.009) with the reported harms including somnolence, ataxia, nausea, tremor and nystagmus This hypothesis-generating work strongly supports the need for further trials to best delineate clinical differences in the GABA analogues. PMID- 26162538 TI - Effect of cardiac resynchronization therapy on patients with heart failure and narrow QRS complexes: a meta-analysis of five randomized controlled trials. AB - PURPOSE: Although cardiac resynchronization therapy (CRT) has been demonstrated extensively to benefit heart failure (HF) patients with wide QRS complexes, the effect of CRT in patients with narrow QRS complexes remains unclear. This meta analysis aimed to determine whether HF patients with narrow QRS complexes may benefit from CRT. METHODS: A search of MEDLINE, EMBASE, and Cochrane databases was performed to identify randomized controlled trials (RCTs) that investigated the effect of CRT in HF patients with narrow QRS complexes (< 130 ms). Outcomes included all-cause mortality, heart failure-related death or hospitalization, 6 min walk distance, quality of life ejection fraction, end-systolic volume, and end-diastolic volume. RESULTS: A total of five RCTs involving 1246 HF patients with narrow QRS complexes were included. The frequency of all-cause mortality for patients receiving CRT versus the control group was 10 versus 7 % (relative risk [RR] 1.45, 95 % confidence interval [CI] 1.002 to 2.091, P = 0.049). CRT did not reduce heart failure-related mortality (RR 0.89; 95 % CI 0.52 to 1.54; P = 0.69) or hospitalization (RR 0.99, 95 % CI 0.79 to 1.23, P = 0.91). In addition, CRT did not improve average 6-min walk distance (weighted mean difference [WMD] 39.28 m, 95 % CI -71.04 to 149.61 m, P = 0.49), QOL scores (WMD 0.64 points, 95 % CI 2.15.10 to 3.43 points, P = 0.65), or ejection fraction (WMD 0.90 %, 95 % CI 0.71 to 2.51 %, P = 0.28). CONCLUSIONS: In HF patients with reduced left ventricular ejection fraction (<= 35 %) and narrow QRS complexes (< 130 ms), CRT did not improve clinical or functional outcomes and may actually increase all cause mortality. PMID- 26162539 TI - Improved tumour marker sensitivity in detecting colorectal liver metastases by combined type IV collagen and CEA measurement. AB - Carcinoembryonic antigen (CEA) is the best circulating tumour marker for colorectal liver metastasis (CLM) but has suboptimal sensitivity and specificity. Circulating type IV collagen (COLIV) is a new potential CLM marker. Here, COLIV and CEA were measured in patients with resectable CLM. COLIV levels were also related to the type of CLM. The prognostic value of these markers and the type of CLM on survival was evaluated. Preoperative plasma samples (n = 94) from patients (n = 85) with CLM undergoing liver resection were used. Seven patients underwent repeated liver resection. Samples from 118 healthy individuals served as control. Samples after liver resection (n = 27) were analysed and related to recurrence. COLIV and CEA levels were analysed, and the type of CLM was classified using paraffinated tissue. Results were analysed by logistic regression and receiver operating characteristic (ROC) curve analysis. CLM patients had significantly elevated levels of COLIV compared to controls (p = 0.001). The sensitivity of COLIV was not better than CEA, but improved sensitivity for detecting CLM was observed with a combination of the two markers compared to using either marker alone (p = 0.001). Circulating COLIV was elevated in 81 % and CEA in 56 % of CLM patients at diagnosis, and high marker levels were related to poor survival. In follow-up samples (n = 27), patients with CLM recurrence (n = 14) had significantly elevated COLIV levels compared to patients without postoperative recurrence (n = 10) (p = 0.001). COLIV is a promising tumour marker for CLM and can possibly be used to detect postoperative CLM recurrence. The combination of COLIV and CEA is superior to either marker alone in detecting CLM. PMID- 26162541 TI - The possible role of EZH2 and DNMT1 polymorphisms in sporadic triple-negative breast carcinoma in southern Chinese females. AB - Triple-negative breast cancer (TNBC) has a more invasive and metastatic potential than the other types of breast cancer and hence is associated with poor prognosis. Zeste homolog 2 (EZH2) and DNA methyltransferase 1 (DNMT1) could lead to tumorigenesis by separately methylating histone H3K27 and CpG islands in tumor suppressor genes. In order to investigate the association between oncogenesis and the distribution of single nucleotide polymorphisms (SNPs) of EZH2, DNMT1, a case control study on SNPs in TNBC cases from south China was conducted. A total of 13 SNPs were genotyped from 234 cases of TNBC tissues, and 300 normal blood samples from age-matched control group were analyzed using Snapshot technology. The expressions of EZH2 and DNMT1 were examined in the 234 cases of TNBC tissues by immunohistochemistry (IHC). The T allele of rs2288349 and the C allele of rs16999593 increase the risk of TNBC, with relative risk coefficients of 1.76 and 1.69, respectively (p < 0.001). The TC genotypes of rs2288349 and rs16999593 were higher in TNBC compared with the control group; the cancer risk increased to 5.27 and 4.13, respectively (p < 0.001). There were no significant differences between the frequencies of the other 10 SNPs and the risk of TNBC (p > 0.05). Five common haplotypes (>8 % frequency) were identified with a cumulative frequency of 96 % in the controls, while the haplotypes of AAGTAG, GGGTGA, and GACCAG were significantly increased in the control group compared to that in patients (p < 0.05). The G allele of rs10274701 significantly increased the EZH2 expression level in TNBC (p = 0.01). This is the first study to demonstrate a significant association between TNBC risk and the polymorphisms of EZH2 and DNMT1, and our researches indicate that the SNPs of EZH2 and DNMT1 are risk predictors for TNBC. PMID- 26162540 TI - Nonsecreted cytoplasmic alpha-fetoprotein: a newly discovered role in intracellular signaling and regulation. An update and commentary. AB - The concept of a non-secreted cytoplasmic-bound form of alpha-fetoprotein is not a new notion in AFP biological activities. Cytoplasmic AFP (CyAFP) is a long known but forgotten protein in search of a function other than a histochemical biomarker. In this report, CyAFP is presented as an "old" protein with a newly described intracellular function. In 1976, CyAFP was shown to be a product of hepatoma cells utilizing 14Cleucine incorporation and demonstrated by autoradiographic procedures. The synthesis of CyAFP without secretion was demonstrated to occur in both malignant and non-malignant cells encompassing hepatomas, ascite fluid cells, immature rodent uterus, MCF-7 breast cancers, and cytosols from human breast cancer patients. Using computer protein matching and alignments in AFP versus members of the nuclear receptor superfamily, a consecutive series of leucine zipper (heptad) repeats in AFP was previously reported, suggesting the possibility for protein-to-protein interactions. The potential for heptad heterodimerization between protein-binding partners provided the rationale for proposing that CyAFP might have the capability to form molecular hetero-complexes with cytoplasmic based transcription factors. More recent investigations have now provided experimental evidence that CyAFP is capable of colocalizing and interacting with transcription-associated factors. Such proteins can modulate intracellular signaling leading to regulation of transcription factors and initiation of growth in human cancer cells. Although circulating serum AFP is known as a growth-enhancing factor during development, cytoplasmic AFP has a lethal role in the oncogenesis, growth, and metastasis of adult liver cancer. PMID- 26162542 TI - A common variant near BDNF is associated with dietary calcium intake in adolescents. AB - Specific targets for most obesity candidate genes discovered by genomewide association studies remain unknown. Such genes are often highly expressed in the hypothalamus, indicating their role in energy homeostasis. We aimed to evaluate the associations of selected gene variants with adiposity and dietary traits. Anthropometric parameters, fat mass, dietary intake (total energy, fat, protein, carbohydrate, fiber, and calcium) and 10 gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R and FTO) were analyzed in 1953 Czech individuals aged 10.0 to 18.0 years (1035 nonoverweight and 918 overweight: body mass index [BMI] >=90th percentile). Obesity risk alleles of TMEM18 rs7561317, SEC16B rs10913469, and FTO rs9939609 were related to increased body weight and BMI (P < .005). The FTO variant also showed a significant positive association with waist circumference and fat mass (P < .001). Overweight adolescents had a lower total energy intake (P < .001) but a higher percentage of fat (P = .009) and protein intake (P < .001) than the nonoverweight subjects. There was also a lower calcium intake in the overweight group (P < .001). An association with at least one component of dietary intake was found in 3 of 10 studied gene variants. The MC4R rs17782313 was associated negatively with protein (P = .012) and positively associated with fiber (P = .032) intakes. The obesity risk alleles of BDNF rs925946 and FTO rs9939609 were related to a lower calcium intake (P = .001 and .037). The effects of FTO and MC4R variants, however, disappeared after corrections for multiple testing. Our results suggest that the common BDNF variant may influence dietary calcium intake independent of BMI. PMID- 26162543 TI - Rhizoma Anemarrhenae extract ameliorates hyperglycemia and insulin resistance via activation of AMP-activated protein kinase in diabetic rodents. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Anemarrhenae has been used in Asian countries for thousands of years to treat diabetes. Insulin resistance (IR) is the primary cause responsible for type 2 diabetes. The aim of this study was to to assess the hypoglycemic and insulin sensitizing properties of Rhizoma Anemarrhenae extract (TFA) in animal models of insulin resistance and/or diabetes and to delineate modes of action. MATERIALS AND METHODS: In-vivo studies were performed on STZ-induced diabetic mice and KK-Ay mice, the former of which were given the extract alone or in combination with insulin for 7 days, and the latter of which were given the extract for 8 consecutive weeks. Fasting blood glucose and serum insulin levels were measured. Pancreatic tissue sections were examined using transmission electron micrographs. Further, hyperinsulinemic-euglycemic clamping study was conducted in BCG vaccine-induced insulin resistance rats, and glucose infusion rate was examined. Mechanisms of action were investigated in 3T3 L1 and Hela cells using Western blot analysis. RESULTS: Our study showed that TFA enhanced the glucose-lowering effects of exogenous insulin administration in STZ induced diabetic mice. Therapeutic administration of TFA significantly reduced fasting blood glucose, and serum insulin levels, and markedly increased the size and the number of insulin-producing beta cells in KK-Ay mice. Further, hyperinsulinemic-euglycemic clamping study showed that glucose infusion rate was significantly improved in TFA-treated BCG vaccine-induced insulin resistance rats. Study of mechanism of action revealed that TFA increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in 3T3-L1 cells. It activates AMPK in a LKB1-independent manner, providing a unified explanation for the beneficial effects of TFA. CONCLUSIONS: This study that TFA mediates activation of AMPK and improves overall glucose and lipid metabolism in diabetic rodents, highlights the potential utility of TFA for the management of type 2 diabetes. PMID- 26162544 TI - Amisulpride and symptomatic bradycardia: a case report. AB - OBJECTIVE: Amisulpride is a second-generation antipsychotic agent indicated for the treatment of schizophrenia and other major psychotic illnesses. Amisulpride induced bradycardia is a rare condition of unknown etiology and mechanism. Asymptomatic bradycardia has been associated with amisulpride in only two cases. In our case, the association was rated as "probable" on the Naranjo adverse drug reaction probability scale. METHOD: Case report. RESULTS: A 45-year-old male patient developed symptomatic bradycardia during usage of amisulpride (400-800 mg/day), which dramatically improved after the complete termination of amisulpride usage. The psychiatric condition remained relatively stable without bradycardia after administration of another antipsychotic agent [risperidone (3 mg/day)]. CONCLUSION: This is the first case report of symptomatic bradycardia associated with the use of amisulpride. Although bradycardia is a rare adverse reaction to antipsychotics, this finding may alert psychiatrists and physicians to this antipsychotic drug side effect. Further study is needed to disclose the role of antipsychotics in bringing about symptomatic bradycardia. PMID- 26162545 TI - Catatonia vis-a-vis delirium: the significance of recognizing catatonia in altered mental status. AB - BACKGROUND: Catatonia is seldom considered in evaluation of altered mental status (AMS) in medical settings. Furthermore, catatonia often meets delirium criteria due to incoherence, altered awareness and behavioral change. Catatonia may co occur with or be preferentially diagnosed as delirium. METHODS: We conducted a systematic literature review of MEDLINE, EMBASE and PsycINFO on the relationship between catatonia and delirium. We also juxtapose clinical features of these syndromes and outline a structured approach to catatonia evaluation and management in acute medical settings. RESULTS: These syndromes share tremendous overlap: the historical catatonia-related terms "delirious mania" and "delirious depression" bespeak of literal confusion differentiating them. Only recently has evidence on their relationship progressed beyond case series and reports. Neurological conditions account for the majority of medical catatonia cases. CONCLUSIONS: New-onset catatonia warrants a medical workup, and catatonic features in AMS may guide clinicians to a neurological condition (e.g., encephalitis, seizures or structural central nervous system disease). Lorazepam or electroconvulsive therapy (ECT) should be considered even in medical catatonia, and neuroleptics should be used with caution. Moreover, ECT may prove lifesaving in malignant catatonia. Further studies on the relationship between delirium and catatonia are warranted. PMID- 26162547 TI - Computational analyses of different intervertebral cages for lumbar spinal fusion. AB - Lumbar spinal fusion is the most common approach for treating spinal disorders such as degeneration or instability. Although this procedure has been performed for many years, there are still important challenges that must be overcome and questions that need to be addressed regarding the high rates of non-union. The present finite element model study aimed to investigate the influence of different cage designs on the fusion process. An axisymmetric finite element model of a spinal segment with an interbody fusion cage was used. The fusion process was based on an existing mechano-regulation algorithm for tissue formation. With this model, the following principal concepts of cage design were investigated: (1) different cage geometries with constant compressive stiffness and (2) cage designs optimized to provide the ideal mechanical stimulus for bone formation, first at the beginning of fusion and then throughout the entire fusion process. The cage geometry substantially influenced the fusion outcome. A cage that created an optimized initial mechanical stimulus did not necessarily lead to accelerated fusion, but rather resulted in delayed fusion or non-union. In contrast, a cage made of a degradable material produced a significantly higher amount of bone and resulted in higher segmental stiffness. However, different compressive loads (250, 500 and 1000 N) substantially affected the amount of newly formed bone tissue. The results of the present study suggest that aiming for an optimal initial mechanical stimulus may be misleading because the initial mechanical environment is not preserved throughout the bone modeling process. PMID- 26162546 TI - Shear loads induce cellular damage in tendon fascicles. AB - Tendon is vital to musculoskeletal function, transferring loads from muscle to bone for joint motion and stability. It is an anisotropic, highly organized, fibrous structure containing primarily type I collagen in addition to tenocytes and other extracellular matrix components contributing to maintenance and function. Tendon is generally loaded via normal stress in a longitudinal direction. However, certain situations, including fiber breakage, enzymatic remodeling, or tendon pathology may introduce various degrees of other loading modalities, such as shear-lag at the fiber level, potentially affecting cellular response and subsequent function. Fascicles from rat tail tendon were dissected and placed in one of three paired groups: intact, single laceration, or double laceration. Each pair had a mechanically tested and control specimen. Single laceration fascicles contained one transverse laceration to mimic a partial tear. Double laceration fascicles had overlapping, longitudinally separated lacerations on opposite sides to cause intra-fascicular shear transfer to be the primary mechanism of loading. Elastic properties of the fascicle, e.g. peak load, steady state load, and stiffness, decreased from intact to single laceration to double laceration groups. Surprisingly, 45% of the intact strength was maintained when shear was the primary internal load transfer mechanism. Cellular viability decreased after mechanical testing in both laceration groups; cell death appeared primarily in a longitudinal plane where high shear load transfer occurred. This cell death extended far from the injury site and may further compromise an already damaged tendon via enzymatic factors and subsequent remodeling associated with cell necrosis. PMID- 26162548 TI - The capacity of the human iliotibial band to store elastic energy during running. AB - The human iliotibial band (ITB) is a poorly understood fascial structure that may contribute to energy savings during locomotion. This study evaluated the capacity of the ITB to store and release elastic energy during running, at speeds ranging from 2-5m/s, using a model that characterizes the three-dimensional musculoskeletal geometry of the human lower limb and the force-length properties of the ITB, tensor fascia lata (TFL), and gluteus maximus (GMax). The model was based on detailed analyses of muscle architecture, dissections of 3-D anatomy, and measurements of the muscles' moment arms about the hip and knee in five cadaveric specimens. The model was used, in combination with measured joint kinematics and published EMG recordings, to estimate the forces and corresponding strains in the ITB during running. We found that forces generated by TFL and GMax during running stretch the ITB substantially, resulting in energy storage. Anterior and posterior regions of the ITB muscle-tendon units (MTUs) show distinct length change patterns, in part due to different moment arms at the hip and knee. The posterior ITB MTU likely stores more energy than the anterior ITB MTU because it transmits larger muscle forces. We estimate that the ITB stores about 1J of energy per stride during slow running and 7J during fast running, which represents approximately 14% of the energy stored in the Achilles tendon at a comparable speed. This previously unrecognized mechanism for storing elastic energy may be an adaptation to increase human locomotor economy. PMID- 26162549 TI - Biomechanics and strain mapping in bone as related to immediately-loaded dental implants. AB - The effects of alveolar bone socket geometry and bone-implant contact on implant biomechanics, and resulting strain distributions in bone were investigated. Following extraction of lateral incisors on a cadaver mandible, implants were placed immediately and bone-implant contact area, stability implant biomechanics and bone strain were measured. In situ biomechanical testing coupled with micro X ray microscopy (u-XRM) illustrated less stiff bone-implant complexes (701-822 N/mm) compared with bone-periodontal ligament (PDL)-tooth complexes (791-913 N/mm). X-ray tomograms illustrated that the cause of reduced stiffness was due to limited bone-implant contact. Heterogeneous elemental composition of bone was identified by using energy dispersive X-ray spectroscopy (EDS). The novel aspect of this study was the application of a new experimental mechanics method, that is, digital volume correlation, which allowed mapping of strains in volumes of alveolar bone in contact with a loaded implant. The identified surface and subsurface strain concentrations were a manifestation of load transferred to bone through bone-implant contact based on bone-implant geometry, quality of bone, implant placement, and implant design. 3D strain mapping indicated that strain concentrations are not exclusive to the bone-implant contact regions, but also extend into bone not directly in contact with the implant. The implications of the observed strain concentrations are discussed in the context of mechanobiology. Although a plausible explanation of surgical complications for immediate implant treatment is provided, extrapolation of results is only warranted by future systematic studies on more cadaver specimens and/or in vivo models. PMID- 26162550 TI - Can visual information encoded in cortical columns be decoded from magnetoencephalography data in humans? AB - It is a principal open question whether noninvasive imaging methods in humans can decode information encoded at a spatial scale as fine as the basic functional unit of cortex: cortical columns. We addressed this question in five magnetoencephalography (MEG) experiments by investigating a columnar-level encoded visual feature: contrast edge orientation. We found that MEG signals contained orientation-specific information as early as approximately 50 ms after stimulus onset even when controlling for confounds, such as overrepresentation of particular orientations, stimulus edge interactions, and global form-related signals. Theoretical modeling confirmed the plausibility of this empirical result. An essential consequence of our results is that information encoded in the human brain at the level of cortical columns should in general be accessible by multivariate analysis of electrophysiological signals. PMID- 26162551 TI - Neurocognitive evidence for mental imagery-driven hypoalgesic and hyperalgesic pain regulation. AB - Mental imagery has the potential to influence perception by directly altering sensory, cognitive, and affective brain activity associated with imagined content. While it is well established that mental imagery can both exacerbate and alleviate acute and chronic pain, it is currently unknown how imagery mechanisms regulate pain perception. For example, studies to date have been unable to determine whether imagery effects depend upon a general redirection of attention away from pain or focused attentional mechanisms. To address these issues, we recorded subjective, behavioral and ERP responses using 64-channel EEG while healthy human participants applied a mental imagery strategy to decrease or increase pain sensations. When imagining a glove covering the forearm, participants reported decreased perceived intensity and unpleasantness, classified fewer high-intensity stimuli as painful, and showed a more conservative response bias. In contrast, when imagining a lesion on the forearm, participants reported increased pain intensity and unpleasantness, classified more low-intensity stimuli as painful, and displayed a more liberal response bias. Using a mass-univariate approach, we further showed differential modulation of the N2 potentials across conditions, with inhibition and facilitation respectively increasing and decreasing N2 amplitudes between 122 and 180 ms. Within this time window, source localization associated inhibiting vs. facilitating pain with neural activity in cortical regions involved in cognitive inhibitory control and in the retrieval of semantic information (i.e., right inferior frontal and temporal regions). In contrast, the main sources of neural activity associated with facilitating vs. inhibiting pain were identified in cortical regions typically implicated in salience processing and emotion regulation (i.e., left insular, inferior-middle frontal, supplementary motor and precentral regions). Overall, these findings suggest that the content of a mental image directly alters pain-related decision and evaluative processing to flexibly produce hypoalgesic and hyperalgesic outcomes. PMID- 26162552 TI - Dynamic coherence analysis of resting fMRI data to jointly capture state-based phase, frequency, and time-domain information. AB - Many approaches for estimating functional connectivity among brain regions or networks in fMRI have been considered in the literature. More recently, studies have shown that connectivity which is usually estimated by calculating correlation between time series or by estimating coherence as a function of frequency has a dynamic nature, during both task and resting conditions. Sliding window methods have been commonly used to study these dynamic properties although other approaches such as instantaneous phase synchronization have also been used for similar purposes. Some studies have also suggested that spectral analysis can be used to separate the distinct contributions of motion, respiration and neurophysiological activity from the observed correlation. Several recent studies have merged analysis of coherence with study of temporal dynamics of functional connectivity though these have mostly been limited to a few selected brain regions and frequency bands. Here we propose a novel data-driven framework to estimate time-varying patterns of whole-brain functional network connectivity of resting state fMRI combined with the different frequencies and phase lags at which these patterns are observed. We show that this analysis identifies both broad-band cluster centroids that summarize connectivity patterns observed in many frequency bands, as well as clusters consisting only of functional network connectivity (FNC) from a narrow range of frequencies along with associated phase profiles. The value of this approach is demonstrated by its ability to reveal significant group differences in males versus females regarding occupancy rates of cluster that would not be separable without considering the frequencies and phase lags. The method we introduce provides a novel and informative framework for analyzing time-varying and frequency specific connectivity which can be broadly applied to the study of the healthy and diseased human brain. PMID- 26162554 TI - Improved sensitivity and specificity for resting state and task fMRI with multiband multi-echo EPI compared to multi-echo EPI at 7 T. AB - A multiband multi-echo (MBME) sequence is implemented and compared to a matched standard multi-echo (ME) protocol to investigate the potential improvement in sensitivity and spatial specificity at 7 T for resting state and task fMRI. ME acquisition is attractive because BOLD sensitivity is less affected by variation in T2*, and because of the potential for separating BOLD and non-BOLD signal components. MBME further reduces TR thus increasing the potential reduction in physiological noise. In this study we used FSL-FIX to clean ME and MBME resting state and task fMRI data (both 3.5mm isotropic). After noise correction, the detection of resting state networks improves with more non-artifactual independent components being observed. Additional activation clusters for task data are discovered for MBME data (increased sensitivity) whereas existing clusters become more localized for resting state (improved spatial specificity). The results obtained indicate that MBME is superior to ME at high field strengths. PMID- 26162555 TI - Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. AB - Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl) 5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non cancerous dividing cells during chemotherapy. PMID- 26162553 TI - Estimating individual contribution from group-based structural correlation networks. AB - Coordinated variations in brain morphology (e.g., cortical thickness) across individuals have been widely used to infer large-scale population brain networks. These structural correlation networks (SCNs) have been shown to reflect synchronized maturational changes in connected brain regions. Further, evidence suggests that SCNs, to some extent, reflect both anatomical and functional connectivity and hence provide a complementary measure of brain connectivity in addition to diffusion weighted networks and resting-state functional networks. Although widely used to study between-group differences in network properties, SCNs are inferred only at the group-level using brain morphology data from a set of participants, thereby not providing any knowledge regarding how the observed differences in SCNs are associated with individual behavioral, cognitive and disorder states. In the present study, we introduce two novel distance-based approaches to extract information regarding individual differences from the group level SCNs. We applied the proposed approaches to a moderately large dataset (n=100) consisting of individuals with fragile X syndrome (FXS; n=50) and age matched typically developing individuals (TD; n=50). We tested the stability of proposed approaches using permutation analysis. Lastly, to test the efficacy of our method, individual contributions extracted from the group-level SCNs were examined for associations with intelligence scores and genetic data. The extracted individual contributions were stable and were significantly related to both genetic and intelligence estimates, in both typically developing individuals and participants with FXS. We anticipate that the approaches developed in this work could be used as a putative biomarker for altered connectivity in individuals with neurodevelopmental disorders. PMID- 26162556 TI - Metabolism of Chuanxiong Rhizoma decoction: Identification of the metabolites in WZS-miniature pig urine. AB - Chuanxiong Rhizoma (CR), a well-known traditional Chinese medicine originated from the rhizome of Ligusticum chuanxiong Hort., was effective for treating various vascular diseases. To identify the metabolites of CR in vivo, the drug containing urine samples of WZS-miniature pigs after orally administrated CR decoction were collected, after sequential column chromatography 17 metabolites (M1-M17) were isolated from the methanol extract of the urine samples. Their structures, including nine phthalides (M1-M9) and eight phenolic acids (M10-M17), were identified by spectroscopic means. Among them, 8 were new ones (M1-M6, M11 M12). On the basis of the structures of identified metabolites, seven original constituents, including 2 phthalides (senkyunolideI/H) and 5 phenolic acids (ferulic acid, isoferulic acid, caffeic acid, 3-hydroxycinnamoyl acid and 4 hydroxybenzonic acid) were deduced to be the major absorbed original constituents of CR in vivo. This is the first study on the metabolites of CR decoction in non rodent animal (WZS-miniature pig), the results will give an insight into the metabolism profiles of phthalides and phenolic acids in CR decoction in vivo. PMID- 26162557 TI - The longitudinal association between psychotic experiences, depression and suicidal behaviour in a population sample of adolescents. AB - PURPOSE: Whilst psychotic experiences are associated with suicidal behaviour in a number of studies the value of psychotic experiences for the prediction of suicidal behaviour and the role of depressive symptoms in this relationship is not clear. We examined the association between psychotic experiences and subsequent suicidal behaviour and examine the role of depressive symptoms in this relationship. METHODS: Psychotic experiences and depressive symptoms at age 12 and 16 years, and suicidal behaviour at age 16 years were assessed in participants (prospective analysis n = 3171; cross-sectional analysis n = 3952) from a population-based cohort. RESULTS: Psychotic experiences (OR 1.75 95 % CI 1.20, 2.54) and depression (OR 3.97 95 % CI 2.56, 6.15) at 12 years were independently associated with suicidal behaviour at 16 years after adjustment for confounding. There was no evidence that the relationship between psychotic experiences and suicidal behaviour was stronger in participants who were also depressive. A ROC analysis showed that adding information on psychotic experiences to measures of depressive symptoms had hardly any effect on improving prediction of suicidal behaviour (AUC increased from 0.64 to 0.65). Whereas adding a measure of depressive symptoms to the measure of psychotic experiences improved prediction substantially (AUC 0.56-0.65). CONCLUSIONS: Psychotic experiences and depression are independently associated with suicidal behaviour although the association with depression is substantially stronger. Psychotic experiences alone are not a strong predictor of later suicidal behaviour and add little to predicting the risk of suicidal behaviour over and above the information provided by depressive symptoms. PMID- 26162558 TI - Management of Pain and Quality of Life in Patients with Chronic Kidney Disease Undergoing Hemodialysis. AB - An important dimension that influences the quality of life of hemodialysis patients is the pain they experience. Quality of life and self-efficacy in pain can play an important role in chronic kidney disease and treatment outcomes. The purpose of the study was to examine self-efficacy in pain and quality of life among patients with end stage renal disease undergoing hemodialysis. Between April 2013 and June 2013, 224 hemodialysis patients completed the Missoula-VITAS Quality of Life Index-15 and the Pain Self-Efficacy Questionnaire. The study was conducted in four dialysis units in hospitals of the Peloponnese region. Sociodemographic data of patients and their individual medical history were recorded. Statistical analysis was performed using SPSS version 19. The more effective the self-efficacy in pain, the lower the quality of life enjoyed by hemodialysis patients. The majority of respondents described the overall quality of life as "moderate," while the self-efficacy in pain depended on comorbidity or complications that accompany the process of hemodialysis. The findings of this study can be used in the development and improvement of health services for the management of patients. Healthcare professionals should understand the concerns and treat the symptoms of patients that affect quality of life, providing thereby holistic health care. PMID- 26162559 TI - Use of Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy in Direct, Nondestructive, and Rapid Assessment of Developmental Cotton Fibers Grown In Planta and in Culture. AB - Cotton fibers are routinely harvested from cotton plants (in planta), and their end-use qualities depend on their development stages. Cotton fibers are also cultured in controlled laboratory environments, so that cotton researchers can investigate many aspects of experimental protocols in cotton breeding programs at reduced expenses. In this work, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectra of cotton fibers grown in planta and in culture were collected to explore the potential of FT-IR technique as a simple, rapid, and direct method for characterizing the fiber development. Complementary to visual inspection of spectral variations, principal component analysis (PCA) of ATR FT IR spectra revealed the occurrence of phase transition from primary to secondary cell wall synthesis and also the difference of starting the phase transition between two types of fibers. Like PCA observation, three simple algorithms were capable of monitoring the secondary cell wall formation effectively. Interestingly and uniquely, simple algorithms were able to detect the subtle discrepancies in fibers older than 25 days post-anthesis, which was not apparent from PCA results. The observation indicated the feasibility of FT-IR technique in rapid, routine, nondestructive, and direct assessment of fiber development for cotton physiology and breeding applications. PMID- 26162560 TI - Prevalence of Dirofilaria immitis in dogs from Barcelona: Validation of a geospatial prediction model. AB - Like other vector borne infections, the distribution of dirofilariosis caused by Dirofilaria immitis is influenced by climatic factors, which regulate the diversity and abundance of mosquito species able to transmit the parasite. Geographical Information Systems (GIS) can predict the distribution and epidemiological behavior of dirofilariosis based on temperature and humidity data. This study analyses the prevalence and current distribution of canine dirofilariosis in the province of Barcelona (Northeastern Spain), and uses a GIS model to evaluate the relationship between the spatial distribution of positive cases and different geo-environmental factors. Canine dirofilariosis is present in all the studied regions but unevenly distributed. The general prevalence is 2.4%, being located most of positive dogs in areas where the model predict both high number of annual generations of D. immitis in vectors and humidity, as a consequence of the presence of irrigated crops or the proximity to the sea. Furthermore, in the urban area of Barcelona, infected dogs were located in districts surrounded or close to parks and green areas. The model can be used as a tool to determine the need of implementation of prophylactic protocols in pets living in municipalities from these regions, based on the geo-environmental characteristics of the area. PMID- 26162561 TI - Dermatobia hominis: Potencial risk of resistance to macrocyclic lactones. AB - Dermatobia hominis is an ectoparasite that infests various species of mammals, including cattle, impairing the quality of cowhides and leather. After observing natural infestation with D. hominis larvae in cattle on two farms in the state of Sao Paulo, Brazil, we evaluated the efficacy of two macrocyclic lactones, ivermectin and moxidectin, against this parasite. The drugs were administered to 10 animals in each group, following the manufacturer's instructions. The groups were: Group 1-treated with ivermectin (0.2mg/kg of body weight (BW)); Group 2 treated with moxidectin (0.2mg/kg BW); and Group 3-control (untreated). On the farm in Pardinho, a total of 12 and 16 live larvae were found in 6 and in 8 animals 10 days after the treatment with ivermectin and moxidectin, respectively, while in the control group 4 bovines had a total of 7 live larvae. On the farm in Anhembi, 2, 4 and 6 live larvae were extracted from ivermectin, moxidectin and control groups, respectively, after the treatment. This is the first report of the presence of live D. hominis larvae after the treatment of cattle with ivermectin and moxidectin in Brazil. PMID- 26162562 TI - Polymorphisms in alternative splicing associated genes are associated with lung cancer risk in a Chinese population. AB - BACKGROUND: Alternative splicing is an important biological step during mRNA processing. Misregulation of alternative splicing can produce aberrant protein isoforms, thus contributing to cancer. We hypothesized that variants in 5 critical splicing factor-associated genes might play an important role in carcinogenesis of lung cancer. MATERIALS AND METHODS: A case-control study including 1,341 non-small cell lung cancer (NSCLC) cases and 1,982 cancer-free controls were conducted to evaluate the associations of 16 tagging/functional polymorphisms in 5 splicing factor-associated genes with lung cancer risk. RESULTS: We found altogether 8 SNPs were associated with lung cancer risk with adjustment of age, gender, and smoking status after multiple corrections (FDR). Among these, six SNPs were related with SRSF7(rs10197412, OR (95% CI)=1.23 (1.06 1.43), P for FDR=0.018; rs12621103, OR(95% CI)=1.25 (1.08-1.46), P for FDR=0.016; rs13024811, OR (95% CI)=1.25 (1.07-1.46), P for FDR=0.016; rs2037875, OR (95% CI)=1.23 (1.06-1.42), P for FDR=0.018; rs3134628, OR (95% CI)=1.25(1.07-1.45), P for FDR=0.016 and rs6715866, OR (95% CI)=1.23 (1.07-1.43), P for FDR=0.016); one SNP was near PTBP2 (rs12566237: OR (95% CI)=1.16 (1.05-1.28), P for FDR=0.016) and one SNP in HNRNPQ (rs16876385: OR (95% CI)=1.17 (1.04-1.32), P for FDR=0.022). CONCLUSIONS: Our findings indicated that genetic variants in these splicing-associated genes might modify individual susceptibility to lung cancer in Chinese population. Further large-scale well-formed population studies and functional researches are warranted to confirm our findings. PMID- 26162563 TI - Clinical pharmacokinetics, safety, and preliminary efficacy evaluation of icotinib in patients with advanced non-small cell lung cancer. AB - OBJECTIVES: To receive pharmacokinetics, safety, and anti-tumor activity of icotinib, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), in patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients (n=40) with advanced NSCLC were enrolled to receive escalating doses of icotinib, which was administrated on Day 1 followed by 28-day continuous dosing starting from Day 4. Four dosing regimens, 100mg b.i.d., 150 mg b.i.d., 125 mg t.i.d., and 200mg b.i.d. were studied. Pharmacokinetics (PK), safety, and efficacy of icotinib were evaluated. RESULTS: Icotinib was well tolerated in Chinese patients with refractory NSCLC. No toxicity with >3 grades were reported in more than 2 patients under any dose levels. One complete response (3%) and 9 partial responses (23%) were received. Total disease control rate could reach at 73% and median progress-free survival (range) was 154 (17-462) days. PK exposure of icotinib increased with increase of dose in NSCLC patients. Food was suggested to increase PK exposure by ~30%. Mean t1/2beta was within 5.31-8.07 h. No major metabolite (>10% plasma exposure of icotinib) was found in NSCLC patients. CONCLUSIONS: Icotinib with up to 400 mg/day exhibited good tolerance and preliminary antitumor activity in Chinese NSCLC patients. Pharmacokinetics of icotinib and 5 major metabolites were fully investigated in NSCLC patients. Optimized biologic dose (OBD) was finally recommended to be 125 mg t.i.d. for the later clinical study. PMID- 26162564 TI - Second line therapy in malignant pleural mesothelioma: A systematic review. AB - After the implementation of standard first line chemotherapy with platinum and antifolates in pleural mesothelioma, patients are confronted with a need for second line treatment at relapse or progression. We conducted a systematic review of the literature for the activity, effectiveness and toxicity of second line treatment. The results are presented according to the class of drugs: chemotherapy and targeted or biological agent. PMID- 26162565 TI - Antibiotics Clinical Development and Pipeline. AB - There is a constant need for resupply with resistance-breaking antibiotics. Governmental programs and updated regulatory guidance have incentivized mainly small- and medium-sized biopharmaceutical companies to develop novel antibiotics up to market licensure, while major pharma players, with exceptions, have abandoned the space for a perceived lack of a return on their investment. The portfolio of approved drugs has improved over recent years for gram-positive infections, including infections caused by methicillin-resistant Staphylococcus aureus. On the other hand, unmet medical need has surfaced in indications dominated by gram-negative pathogens including complicated intra-abdominal and bloodstream infections as well as hospital-acquired and ventilator-associated pneumonia. Few if any treatment options are left for extended-spectrum beta lactamase- and carbapenemase-producing Enterobacteriaceae, e.g., Klebsiella pneumoniae, and the multi-drug-resistant non-fermenting gram-negative bacteria Pseudomonas aeruginosa and Acinetobacter baumannii. The present paper summarizes and reviews the clinical pipeline of novel antibiotics by clinical indication and identifies the unmet medical need in the space. PMID- 26162566 TI - Cooperative Interaction Within RNA Virus Mutant Spectra. AB - RNA viruses usually consist of mutant spectra because of high error rates of viral RNA polymerases. Growth competition occurs among different viral variants, and the fittest clones predominate under given conditions. Individual variants, however, may not be entirely independent of each other, and internal interactions within mutant spectra can occur. Examples of cooperative and interfering interactions that exert enhancing and suppressing effects on replication of the wild-type virus, respectively, have been described, but their underlying mechanisms have not been well defined. It was recently found that the cooperation between wild-type and variant measles virus genomes produces a new phenotype through the heterooligomer formation of a viral protein. This observation provides a molecular mechanism underlying cooperative interactions within mutant spectra. Careful attention to individual sequences, in addition to consensus sequences, may disclose further examples of internal interactions within mutant spectra. PMID- 26162567 TI - Personalisation of breast cancer follow-up: a time-dependent prognostic nomogram for the estimation of annual risk of locoregional recurrence in early breast cancer patients. AB - The objective of this study was to develop and validate a time-dependent logistic regression model for prediction of locoregional recurrence (LRR) of breast cancer and a web-based nomogram for clinical decision support. Women first diagnosed with early breast cancer between 2003 and 2006 in all Dutch hospitals were selected from the Netherlands Cancer Registry (n = 37,230). In the first 5 years following primary breast cancer treatment, 950 (2.6 %) patients developed a LRR as first event. Risk factors were determined using logistic regression and the risks were calculated per year, conditional on not being diagnosed with recurrence in the previous year. Discrimination and calibration were assessed. Bootstrapping was used for internal validation. Data on primary tumours diagnosed between 2007 and 2008 in 43 Dutch hospitals were used for external validation of the performance of the nomogram (n = 12,308). The final model included the variables grade, size, multifocality, and nodal involvement of the primary tumour, and whether patients were treated with radio-, chemo- or hormone therapy. The index cohort showed an area under the ROC curve of 0.84, 0.77, 0.70, 0.73 and 0.62, respectively, per subsequent year after primary treatment. Model predictions were well calibrated. Estimates in the validation cohort did not differ significantly from the index cohort. The results were incorporated in a web-based nomogram ( http://www.utwente.nl/mira/influence ). This validated nomogram can be used as an instrument to identify patients with a low or high risk of LRR who might benefit from a less or more intensive follow-up after breast cancer and to aid clinical decision making for personalised follow-up. PMID- 26162568 TI - Health care utilization by patients with common variable immune deficiency defined by International Classification of Diseases, Ninth Revision code 279.06. PMID- 26162569 TI - Anaphylaxis as a delayed reaction of methimazole therapy. PMID- 26162570 TI - Omalizumab, an additional therapy for allergic bronchopulmonary aspergillosis. PMID- 26162571 TI - International consensus on allergy immunotherapy. AB - Allergen immunotherapy (AIT) has been used to treat allergic disease since the early 1900s. Despite numerous clinical trials and meta-analyses proving AIT efficacious, it remains underused and is estimated to be used in less than 10% of patients with allergic rhinitis or asthma worldwide. In addition, there are large differences between regions, which are not only due to socioeconomic status. There is practically no controversy about the use of AIT in the treatment of allergic rhinitis and allergic asthma, but for atopic dermatitis or food allergy, the indications for AIT are not well defined. The elaboration of a wider consensus is of utmost importance because AIT is the only treatment that can change the course of allergic disease by preventing the development of asthma and new allergen sensitizations and by inducing allergen-specific immune tolerance. Safer and more effective AIT strategies are being continuously developed both through elaboration of new allergen preparations and adjuvants and alternate routes of administration. A number of guidelines, consensus documents, or both are available on both the international and national levels. The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice. Consequently, the International Collaboration in Asthma, Allergy and Immunology, formed by the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the World Allergy Organization, has decided to issue an international consensus on AIT. PMID- 26162573 TI - Application of a topical vapocoolant spray decreases pain at the site of initial intradermal anaesthetic injection during ultrasound-guided breast needle biopsy. AB - AIM: To assess whether the application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy decreases pain at the site of the initial injection. MATERIALS AND METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study, 50 women aged 49.1 +/ 1.6 years (mean +/- standard error) were recruited and provided written informed consent. Participants served as their own controls and were blinded as to whether a topical vapocoolant spray or a placebo was used immediately prior to the initial local anaesthetic injection at two separate biopsy sites. With the exception of the application of vapocoolant or placebo, the entire ultrasound guided procedure was performed according to a routine protocol. Participants recorded pain at initial injection site on a visual analogue scale. General linear mixed models for repeated measures analysis of variance and a 0.05 significance level were used. RESULTS: Application of topical vapocoolant spray was shown to significantly decrease pain at the site of initial intradermal anaesthetic injection as compared to placebo (p<0.001). Treatment effect was independent of age of the subject, race/ethnicity, operator, type of biopsy device, and histopathology result. No complications from vapocoolant spray use were reported. CONCLUSION: Application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy significantly decreases pain at the site of the initial injection and could contribute to improve the patient's overall procedural experience. PMID- 26162574 TI - Desmoid-type fibromatosis. AB - Desmoid-type fibromatosis is a rare, locally infiltrative, mesenchymal neoplasm that is associated with high rates of local recurrence but lacks the potential to metastasise. The disease affects younger individuals, with a peak age of 30 years, and is the most common cause of an anterior abdominal wall mass in young women of childbearing age. It may, however, involve nearly every body part, including the extremities, head and neck, trunk, and abdominal cavity; as such, desmoid-type fibromatosis may present to a range of general and subspecialty radiologists. These rare tumours have a widely variable clinical presentation and unpredictable natural history, hence input from a soft-tissue tumour centre is recommended, although much of the imaging may be performed at the patient's local hospital. The consensus for treatment has changed over the past decade, with most centres moving away from primary radical surgery towards a front-line 'watch-and wait' policy. Therefore, imaging has an increasingly important role to play in both the diagnosis and follow-up of these patients. This review will discuss the typical imaging characteristics of these lesions and suggest diagnostic and follow-up magnetic resonance imaging protocols, with details of suitable sequences and scanning intervals. PMID- 26162575 TI - Introducing medication abortion into public sector facilities in KwaZulu-Natal, South Africa: an operations research study. AB - OBJECTIVES: Examine the feasibility of introducing mifepristone-misoprostol medication abortion into existing public sector surgical abortion services in KwaZulu-Natal, South Africa. STUDY DESIGN: Cohort study of women offered medication or surgical abortion in a larger medication abortion introduction study. The sample included 1167 women seeking first-trimester abortion at four public sector facilities; 923 women at <=9 weeks' gestation were eligible for medication abortion. Women who chose medication abortion took 200 mg of mifepristone orally at the facility and 800 mcg of misoprostol buccally (or vaginally if they anticipated or experienced problems with buccal administration) 48 h later at home, based on international research and global safe abortion guidelines. Women who chose surgical abortion received 600 mg of misoprostol sublingually or vaginally on the day of their procedure followed by manual vacuum aspiration 4 h later. Main outcome measures included proportion of eligible women who chose each method, proportion with complete abortion and proportion reporting adverse events. RESULTS: Ninety-four percent of eligible women chose medication abortion. No adverse events were reported by women who chose surgical abortion; 3% of women in the medication abortion group reported adverse events and 0.4% reported a serious adverse event. Seventy-six percent of women received a family planning method at the facility where their received their abortion, with no difference based on procedure type. Medication abortion patients were significantly more likely to report they would choose this method again (94% vs. 78%, p<.001) and recommend the method to a friend (98% vs. 84%, p<.001). CONCLUSIONS: Medication abortion was successfully introduced with low and acceptable rates of adverse events; most women at study facilities chose this option. IMPLICATIONS: Mifepristone-misoprostol medication abortion was successfully integrated into public sector surgical abortion services in South Africa and was chosen by a large majority of women who were eligible and offered choice of early termination method; access to medication abortion should be expanded in South Africa and other similar settings. PMID- 26162572 TI - Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies. AB - BACKGROUND: Follicular helper T (TFH) cells underpin T cell-dependent humoral immunity and the success of most vaccines. TFH cells also contribute to human immune disorders, such as autoimmunity, immunodeficiency, and malignancy. Understanding the molecular requirements for the generation and function of TFH cells will provide strategies for targeting these cells to modulate their behavior in the setting of these immunologic abnormalities. OBJECTIVE: We sought to determine the signaling pathways and cellular interactions required for the development and function of TFH cells in human subjects. METHODS: Human primary immunodeficiencies (PIDs) resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Circulating follicular helper T (cTFH) cell subsets, memory B cells, and serum immunoglobulin levels were quantified and functionally assessed in healthy control subjects, as well as in patients with PIDs resulting from mutations in STAT3, STAT1, TYK2, IL21, IL21R, IL10R, IFNGR1/2, IL12RB1, CD40LG, NEMO, ICOS, or BTK. RESULTS: Loss-of-function (LOF) mutations in STAT3, IL10R, CD40LG, NEMO, ICOS, or BTK reduced cTFH cell frequencies. STAT3 and IL21/R LOF and STAT1 gain-of-function mutations skewed cTFH cell differentiation toward a phenotype characterized by overexpression of IFN-gamma and programmed death 1. IFN-gamma inhibited cTFH cell function in vitro and in vivo, as corroborated by hypergammaglobulinemia in patients with IFNGR1/2, STAT1, and IL12RB1 LOF mutations. CONCLUSION: Specific mutations affect the quantity and quality of cTFH cells, highlighting the need to assess TFH cells in patients by using multiple criteria, including phenotype and function. Furthermore, IFN-gamma functions in vivo to restrain TFH cell-induced B-cell differentiation. These findings shed new light on TFH cell biology and the integrated signaling pathways required for their generation, maintenance, and effector function and explain the compromised humoral immunity seen in patients with some PIDs. PMID- 26162576 TI - Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease. AB - OBJECTIVES: Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBFMRI) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values. METHODS: First, we validated RBFMRI measurement using phantoms simulating renal artery hemodynamics. Thereafter, we investigated in a test-set of 21 patients intra- and inter-observer coefficient of variation of RBFMRI. After validation, we measured RBFMRI in a cohort of 91 patients and compared the variability explained by characteristics indicative for disease severity for RBFMRI and RBF measured by continuous hippuran infusion. RESULTS: The correlation in flow measurement using phantoms by phase-contrast MRI was high and fluid collection was high (CCC=0.969). Technical problems that precluded RBFMRI measurement occurred predominantly in patients with a lower eGFR (34% vs. 16%). In subjects with higher eGFRs, variability in RBF explained by disease characteristics was similar for RBFMRI compared to RBFHip, whereas in subjects with lower eGFRs, this was significantly less for RBFMRI. CONCLUSIONS: Our study shows that RBF can be measured accurately in ADPKD patients by phase-contrast, but this technique may be less feasible in subjects with a lower eGFR. KEY POINTS: Renal blood flow (RBF) can be accurately measured by phase-contrast MRI in ADPKD patients. RBF measured by phase-contrast is associated with ADPKD disease severity. RBF measurement by phase-contrast MRI may be less feasible in patients with an impaired eGFR. PMID- 26162577 TI - Comparison of diagnostic accuracy of (111)In-pentetreotide SPECT and (68)Ga DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours. AB - OBJECTIVES: To compare the diagnostic accuracy of (111)In-pentetreotide scintigraphy with (68)Ga-DOTATOC-positron emission tomography (PET)/computed tomography (CT) in patients with metastatic-neuroendocrine tumour (NET) scheduled for peptide receptor radionuclide therapy (PRRT). Incremental lesions (ILs) were defined as lesions observed on only one modality. METHODS: Fifty-three metastatic NET-patients underwent (111)In-pentetreotide-scintigraphy (24 h post-injection; planar+single-photon emission CT (SPECT) abdomen) and whole-body (68)Ga-DOTATOC PET/CT. SPECT and PET were compared in a lesion-by-lesion and organ-by-organ analysis, determining the total lesions and ILs for both modalities. RESULTS: Significantly more lesions were detected on (68)Ga-DOTATOC-PET/CT versus (111)In pentetreotide-scintigraphy. More specifically, we observed 1,098 lesions on PET/CT (range: 1-105; median: 15) versus 660 on SPECT (range: 0-73, median: 9) (p<0.0001), with 439 PET-ILs (42/53 patients) and one SPECT-IL (1/53 patients). The sensitivity for PET/CT was 99.9 % (95 % CI, 99.3-100.0), for SPECT 60.0 % (95 % CI, 48.5-70.2). The organ-by-organ analysis showed that the PET-ILs were most frequently visualized in liver and skeleton. CONCLUSION: Ga-DOTATOC-PET/CT is superior for the detection of NET-metastases compared to (111)In-pentetreotide SPECT. KEY POINTS: Somatostatin receptor PET is superior to SPECT in detecting NET metastases. PET is the scintigraphic method for accurate depiction of NET tumour burden. The sensitivity of PET is twofold higher than the sensitivity of SPECT. PMID- 26162578 TI - Chemical shift MRI can aid in the diagnosis of indeterminate skeletal lesions of the spine. AB - OBJECTIVES: To evaluate the role of chemical shift MRI in the characterisation of indeterminate skeletal lesions of the spine as benign or malignant. METHODS: Fifty-five patients (mean age 54.7 years) with 57 indeterminate skeletal lesions of the spine were included in this retrospective study. In addition to conventional MRI at 3 T which included at least sagittal T1WI and T2WI/STIR sequences, patients underwent chemical shift MRI. A cut-off value with a signal drop-out of 20 % was used to differentiate benign lesions from malignant lesions (signal drop-out <20 % being malignant). RESULTS: There were 45 benign lesions and 12 malignant lesions. Chemical shift imaging correctly diagnosed 33 of 45 lesions as benign and 11 of 12 lesions as malignant. In contrast, there were 12 false positive cases and 1 false negative case based on chemical shift MRI. This yielded a sensitivity of 91.7 %, a specificity of 73.3 %, a negative predictive value of 97.1 %, a positive predictive value of 47.8 % and a diagnostic accuracy of 82.5 %. CONCLUSIONS: Chemical shift MRI can aid in the characterisation of indeterminate skeletal lesions of the spine in view of its high sensitivity in diagnosing malignant lesions. Chemical shift MRI can potentially avoid biopsy in a considerable percentage of patients with benign skeletal lesions of the spine. KEY POINTS: * Differentiating benign from malignant skeletal lesions of the spine can be challenging. * Utility of chemical shift MRI in characterising indeterminate spinal lesion is unreported. * This study demonstrates sensitivity 91.7 %, specificity 73.3 %, diagnostic accuracy 82.5 % for CSI. * CSI is useful in differentiating benign from malignant skeletal spine lesions. * Biopsy can potentially be avoided in some patients with benign skeletal lesions. PMID- 26162579 TI - Comparison of optimised endovaginal vs external array coil T2-weighted and diffusion-weighted imaging techniques for detecting suspected early stage (IA/IB1) uterine cervical cancer. AB - OBJECTIVE: To compare sensitivity and specificity of endovaginal versus external array coil T2-W and T2-W + DWI for detecting and staging small cervical tumours. METHODS: Optimised endovaginal and external array coil MRI at 3.0-T was done prospectively in 48 consecutive patients with stage Ia/Ib1 cervical cancer. Sensitivity/specificity for detecting tumour and parametrial extension against histopathology for a reading radiologist were determined on coronal T2-W and T2W + DW images. An independent radiologist also scored T2-W images without and with addition of DWI for the external-array and endovaginal coils on separate occasions >2 weeks apart. Cohen's kappa assessed inter- and intra-observer agreement. RESULTS: Median tumour volume in 19/38 cases positive on subsequent histology was 1.75 cm(3). Sensitivity, specificity, PPV, NPV were: reading radiologist 91.3 %, 89.5 %, 91.3 %, 89.5 %, respectively; independent radiologist T2-W 82.6 %, 73.7 %, 79.1 %, 77.8 % for endovaginal, 73.9 %, 89.5 %, 89.5 %, 73.9 % for external-array coil. Adding DWI improved sensitivity and specificity of endovaginal imaging (78.2 %, 89.5 %); adding DWI to external-array imaging improved specificity (94.7 %) but reduced sensitivity (66.7 %). Inter- and intra observer agreement on T2-W + DWI was good (kappa = 0.67 and 0.62, respectively). CONCLUSION: Endovaginal coil T2-W MRI is more sensitive than external-array coil for detecting tumours <2 cm(3); adding DWI improves specificity of endovaginal imaging but reduces sensitivity of external-array imaging. KEY POINTS: * Endovaginal more accurate than external-array T2-W MRI for detecting small cervical cancers. * Addition of DWI improves sensitivity and specificity of endovaginal T2-W imaging. * Addition of DWI substantially reduces sensitivity of external-array T2-W imaging. PMID- 26162580 TI - The impact of preoperative axillary ultrasonography in T1 breast tumours. AB - OBJECTIVES: To (a) determine the diagnostic validity of axillary ultrasound (AUS) in pT1 tumours and whether fine-needle aspiration (FNA) improves its diagnostic performance, and (b) determine the negative predictive value (NPV) of AUS in a simulation environment (cutoff: two lymph nodes with macrometastases) in patients fulfilling American College of Surgeons Oncology Group (ACOSOG) Z0011 criteria. MATERIALS AND METHODS: This retrospective multicentre cross-sectional study analysed diagnostic accuracy in 355 pT1 breast cancers. All patients underwent AUS; visible nodes underwent FNA regardless of their AUS appearance. Sentinel node biopsy and axillary lymph node dissection (ALND) were gold standards. Data were analysed considering micrometastases 'positive' and considering micrometastases 'N negative'. The simulation environment included all patients fulfilling ACOSOG Z0011 criteria. RESULTS: Axillary involvement: 22.8 %; AUS sensitivity: 46.9 % (Nmic positive)/66.7 % (Nmic negative); AUS+FNA sensitivity: 52.6 % (pNmic positive)/72.0 % (pNmic negative). In the simulation environment, AUS had 75.0 % sensitivity, 88.9 % specificity and 99.2 % NPV. CONCLUSION: AUS has moderate sensitivity in T1 tumours. As ALND is unnecessary in micrometastases, considering micrometastases 'N negative' increases the practical impact of AUS. In patients fulfilling ACOSOG Z0011 criteria, AUS alone can predict cases unlikely to benefit from ALND. KEY POINTS: * AUS+FNA can predict axillary involvement, thus avoiding SNB. * Not all patients with axillary involvement need ALND. * Axillary tumour load determines axillary management. * AUS could classify patients according to axillary load. PMID- 26162581 TI - Distinction between saltwater drowning and freshwater drowning by assessment of sinus fluid on post-mortem computed tomography. AB - OBJECTIVE: To evaluate the difference in sinus fluid volume and density between saltwater and freshwater drowning and diagnose saltwater drowning in distinction from freshwater drowning. METHODS: Ninety-three drowning cases (22 saltwater and 71 freshwater) were retrospectively investigated; all had undergone post-mortem CT and forensic autopsy. Sinus fluid volume and density were calculated using a 3D-DICOM workstation, and differences were evaluated. Diagnostic performance of these indicators for saltwater drowning was evaluated using a cut-off value calculated by receiver operating characteristic (ROC) analysis. RESULTS: The median sinus fluid volume was 5.68 mL in cases of saltwater drowning (range 0.08 to 37.55) and 5.46 mL in cases of freshwater drowning (0.02 to 27.68), and the average densities were 47.28 (14.26 to 75.98) HU and 32.56 (-14.38 to 77.43) HU, respectively. While sinus volume did not differ significantly (p = 0.6000), sinus density was significantly higher in saltwater than freshwater drowning cases (p = 0.0002). ROC analysis for diagnosis of saltwater drowning determined the cut-off value as 37.77 HU, with a sensitivity of 77 %, specificity of 72 %, PPV of 46 % and NPV of 91 %. CONCLUSION: The average density of sinus fluid in cases of saltwater drowning was significantly higher than in freshwater drowning cases; there was no significant difference in the sinus fluid volume. KEY POINTS: * Sinus fluid density of saltwater drowning is significantly higher than freshwater drowning. * Cut-off value was 37.77 HU based on the ROC analysis. * The cut-off value translated to 91 % NPV for diagnosis of saltwater drowning. PMID- 26162582 TI - Increasing feasibility and utility of (18)F-FDOPA PET for the management of glioma. AB - INTRODUCTION: Despite radical treatment therapies, glioma continues to carry with it a uniformly poor prognosis. Patients diagnosed with WHO Grade IV glioma (glioblastomas; GBM) generally succumb within two years, even those with WHO Grade III anaplastic gliomas and WHO Grade II gliomas carry prognoses of 2-5 and 2 years, respectively. PET imaging with (18)F-FDOPA allows in vivo assessment of the metabolism of glioma relative to surrounding tissues. The high sensitivity of (18)F-DOPA imaging grants utility for a number of clinical applications. METHODS: A collection of published work about (18)F-FDOPA PET was made and a critical review was discussed and written. RESULTS: A number of research papers have been published demonstrating that in conjunction with MRI, (18)F-FDOPA PET provides greater sensitivity and specificity than these modalities in detection, grading, prognosis and validation of treatment success in both primary and recurrent gliomas. In further comparisons with (11)C-MET, (18)F-FLT, (18)F-FET and MRI, (18)F-FDOPA has shown similar or better efficacy. Recently synthesis cassettes have become available, making (18)F-FDOPA more accessible. CONCLUSIONS: According to the available data, (18)F-FDOPA PET is a viable radiotracer for imaging and treatment planning of gliomas. ADVANCES IN KNOWLEDGE AND IMPLICATION FOR PATIENT CARE: (18)F-FDOPA PET appears to be a viable radiopharmaceutical for the diagnosis and treatment planning of gliomas cases, improving on that of MRI and (18)F-FDG PET. PMID- 26162583 TI - Folate receptor-targeted radionuclide therapy: preclinical investigation of anti tumor effects and potential radionephropathy. AB - INTRODUCTION: Application of therapeutic folate radioconjugates is a promising option for the treatment of folate receptor (FR)-positive tumors, although high uptake of radiofolates in the kidneys remains a critical issue. Recently, it was shown that enhancing the blood circulation of radiofolates results in increased tumor uptake and reduced retention of radioactivity in the kidneys. In this study, we investigated and compared the anti-tumor effects and potential long term damage to the kidneys after application of an albumin-binding ((177)Lu cm09), and a conventional ((177)Lu-EC0800) folate radioconjugate. METHODS: In vivo studies were performed with KB tumor-bearing nude mice. (177)Lu-EC0800 and (177)Lu-cm09 were applied at variable quantities (10-30 MBq/mouse), and the tumor growth was monitored over time. Mice without tumors were injected with the same radiofolates and investigated over eight months by determination of creatinine and blood urea nitrogen plasma levels and by measuring renal uptake of (99m)Tc DMSA using SPECT. At the study end, the morphological changes were examined on renal tissue sections using variable staining methods. RESULTS: Compared to untreated controls, dose-dependent tumor growth inhibition and prolonged survival was observed in all treated mice. In line with the resulting absorbed dose, the treatment was more effective with (177)Lu-cm09 than with (177)Lu-EC0800, enabling complete tumor remission after application of >=20MBq (>=28Gy). Application of radiofolates with an absorbed renal dose >=23 Gy showed increased levels of renal plasma parameters and reduced renal uptake of (99m)Tc-DSMA. Morphological changes observed on tissue sections confirmed radionephropathy of variable stages. CONCLUSIONS: (177)Lu-cm09 showed more favorable anti-tumor effects and significantly less damage to the kidneys compared to (177)Lu-EC0800 as was expected based on improved tumor-to-kidney ratios. It was demonstrated that enhancing the blood circulation time of radiofolates was favorable regarding the risk-benefit profile of a therapeutic application. These results hold promise for future translation of the albumin-binder concept to the clinics, potentially enabling FR-targeted radionuclide therapy in patients. PMID- 26162584 TI - Elastin governs the mechanical response of medial collateral ligament under shear and transverse tensile loading. AB - Elastin is a highly extensible structural protein network that provides near elastic resistance to deformation in biological tissues. In ligament, elastin is localized between and along the collagen fibers and fascicles. When ligament is stretched along the primary collagen axis, elastin supports a relatively high percentage of load. We hypothesized that elastin may also provide significant load support under elongation transverse to the primary collagen axis and shear along the collagen axis. Quasi-static transverse tensile and shear material tests were performed to quantify the mechanical contributions of elastin during deformation of porcine medial collateral ligament. Dose response studies were conducted to determine the level of elastase enzymatic degradation required to produce a maximal change in the mechanical response. Maximal changes in peak stress occurred after 3h of treatment with 2U/ml porcine pancreatic elastase. Elastin degradation resulted in a 60-70% reduction in peak stress and a 2-3* reduction in modulus for both test protocols. These results demonstrate that elastin provides significant resistance to elongation transverse to the collagen axis and shear along the collagen axis while only constituting 4% of the tissue dry weight. The magnitudes of the elastin contribution to peak transverse and shear stress were approximately 0.03 MPa, as compared to 2 MPa for axial tensile tests, suggesting that elastin provides a highly anisotropic contribution to the mechanical response of ligament and is the dominant structural protein resisting transverse and shear deformation of the tissue. PMID- 26162585 TI - A Zr-based bulk metallic glass for future stent applications: Materials properties, finite element modeling, and in vitro human vascular cell response. AB - Despite the prevalent use of crystalline alloys in current vascular stent technology, new biomaterials are being actively sought after to improve stent performance. In this study, we demonstrated the potential of a Zr-Al-Fe-Cu bulk metallic glass (BMG) to serve as a candidate stent material. The mechanical properties of the Zr-based BMG, determined under both static and cyclic loadings, were characterized by high strength, which would allow for the design of thinner stent struts to improve stent biocompatibility. Finite element analysis further complemented the experimental results and revealed that a stent made of the Zr based BMG was more compliant with the beats of a blood vessel, compared with medical 316L stainless steel. The Zr-based BMG was found to be corrosion resistant in a simulated body environment, owing to the presence of a highly stable ZrO2-rich surface passive film. Application-specific biocompatibility studies were conducted using human aortic endothelial cells and smooth muscle cells. The Zr-Al-Fe-Cu BMG was found to support stronger adhesion and faster coverage of endothelial cells and slower growth of smooth muscle cells than 316L stainless steel. These results suggest that the Zr-based BMG could promote re endothelialization and potentially lower the risk of restenosis, which are critical to improve vascular stent implantation integration. In general, findings in this study raised the curtain for the potential application of BMGs as future candidates for stent applications. STATEMENT OF SIGNIFICANCE: Vascular stents are medical devices typically used to restore the lumen of narrowed or clogged blood vessel. Despite the clinical success of metallic materials in stent-assisted angioplasty, post-surgery complications persist due to the mechanical failures, corrosion, and in-stent restenosis of current stents. To overcome these hurdles, strategies including new designs and surface functionalization have been exercised. In addition, the development of new materials with higher performance and biocompatibility can intrinsically reduce stent failure rates. The present study demonstrates the advantages of a novel material, named bulk metallic glass (BMG), over the benchmarked 316L stainless steel through experimental methods and computational simulations. It raises the curtain of new research endeavors on BMGs as competitive alternatives for stent applications. PMID- 26162586 TI - Influence of scaffold properties on the inter-relationship between human bone marrow derived stromal cells and endothelial cells in pro-osteogenic conditions. AB - One of the significant challenges in bone tissue engineering is the integration of biomaterials designed to facilitate and stimulate mineralization with a simultaneously rapid rate of angiogenesis and vascularization of the tissue construct, a challenge complicated by our lack of knowledge of the interactions among key cell types and scaffold properties. This study compared functional activity of human bone marrow-derived stromal cells (hMSC) seeded onto a porous salt-leached poly(D,L-lactic acid) (PDLLA) scaffolds, with and without the incorporation of silk fibroin fibers and then further investigated their co culture with human umbilical vein endothelial cells (HUVECs). Cell viability, proliferation, and alkaline phosphatase activity were measured for a range of time points in culture, with osteogenic and angiogenic marker immunolocalization and gene expression at selected stages. Our findings suggest that, despite similar porosity and pore size distribution exhibited by the PDLLA and PDLLA plus silk fibroin scaffolds, there were marked differences in cell distribution and function. In the absence of fibers, a highly osteogenic response was observed in hMSCs in the scaffolds co-cultured with endothelial cells, greater than that observed with hMSCs alone or in either of the scaffolds with fibers added. However, fiber presence clearly better supported endothelial cell cultures, as determined by greater levels of endothelial marker expression at both the gene and protein level after 3 weeks of culture. The design of composite scaffolds integrating beneficial components of differing structures and materials to facilitate appropriate biological responses appears a promising yet challenging avenue of research. STATEMENT OF SIGNIFICANCE: A significant challenge in bone tissue engineering is to promote a rapid vascularization of the tissue construct in parallel to the extracellular matrix mineralization. The design of composite scaffolds integrating beneficial components of differing structures and materials to facilitate appropriate biological responses appears a promising yet challenging avenue of research. Here we investigated cultures of hMSCs and HUVECs on a silk fibroin enhanced PDLLA scaffold, showing that the final output of this in vitro system is not the linear sum of the effects of the single variables. These results are of interest as they demonstrate how the addition of endothelial cells can affect hMSC phenotype and that the output can be further modulated by the introduction of silk fibroin fibers. PMID- 26162587 TI - Piezoelectric materials for tissue regeneration: A review. AB - The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues raised the question whether or not electric fields play an important role in cell function. It has kindled research and the development of technologies in emulating biological electricity for tissue regeneration. Promising effects of electrical stimulation on cell growth and differentiation and tissue growth has led to interest in using piezoelectric scaffolds for tissue repair. Piezoelectric materials can generate electrical activity when deformed. Hence, an external source to apply electrical stimulation or implantation of electrodes is not needed. Various piezoelectric materials have been employed for different tissue repair applications, particularly in bone repair, where charges induced by mechanical stress can enhance bone formation; and in neural tissue engineering, in which electric pulses can stimulate neurite directional outgrowth to fill gaps in nervous tissue injuries. In this review, a summary of piezoelectricity in different biological tissues, mechanisms through which electrical stimulation may affect cellular response, and recent advances in the fabrication and application of piezoelectric scaffolds will be discussed. STATEMENT OF SIGNIFICANCE: The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues has kindled research and the development of technologies using electrical stimulation for tissue regeneration. Piezoelectric materials generate electrical activity in response to deformations and allow for the delivery of an electrical stimulus without the need for an external power source. As a scaffold for tissue engineering, growing interest exists due to its potential of providing electrical stimulation to cells to promote tissue formation. In this review, we cover the discovery of piezoelectricity in biological tissues, its connection to streaming potentials, biological response to electrical stimulation and commonly used piezoelectric materials for tissue regeneration. This review summarizes their potential as a promising scaffold in the tissue engineering field. PMID- 26162588 TI - Transvenous embolization of cavernous sinus dural arteriovenous fistula via angiographic occlusive inferior petrous sinus. AB - BACKGROUND: Trans-inferior petrous sinus (IPS) coil embolization is an efficient and safe method to manage cavernous sinus dural arteriovenous fistulas (CSDAVFs). However, some CSDAVFs may be associated with angiographic occlusive IPS making access difficult. The purpose of this study was to report our experience of transvenous embolization of the CSDAVF via angiographic occlusive IPS. METHODS: We reviewed the cases of 20 patients who underwent transvenous embolization via angiographic occlusive IPS over a 6 year period. The study consisted of seven men and 13 women, ranging from 46 years to 78 years of age (mean, 60 years). We retrospectively analyzed the angioarchitecture of the CSDAVFs, the procedural time and the angiographic as well as the clinical outcomes after embolization. RESULTS: True occlusive IPS was found in 13 of the patients, while patent IPS with compartment of the IPS-CS was demonstrated in the remaining seven patients. The microcatheter was successfully navigated to the fistula site of the CS in 16 patients (80%), while such navigation failed in four patients following numerous attempts. The mean procedural times for truly occlusive IPS and for compartment of the IPS-CS were 111 minutes and 129 minutes, respectively. No recurrent fistula was observed on follow-up neuroimages. Three patients had transient third or sixth cranial nerve palsy, and one patient had perforation of the IPS leading to temporary headache. The mean clinical follow-up period was 18 months. CONCLUSION: Angiographic occlusive IPS of CSDAVF may be related to true occlusion of IPS or patent IPS with compartment of the IPS-CS. There is no statistically significant difference in procedural times for these two different fistula anatomies. Transvenous embolization via angiographic occlusive IPS is a safe and effective method to manage CSDAVFs. PMID- 26162589 TI - WT1 Expression in Adult Granular Cell Tumor of the Vocal Cord and Tongue. PMID- 26162590 TI - Stability, antimicrobial activity, and effect of nisin on the physico-chemical properties of fruit juices. AB - Heat processing is the most commonly used hurdle for inactivating microorganisms in fruit juices. However, this preservation method could interfere with the organoleptic characteristics of the product. Alternative methods have been proposed and bacteriocins such as nisin are potential candidates. However, the approval of bacteriocins as food additives is limited, especially in foods from vegetal origin. We aimed to verify the stability, the effect on physico-chemical properties, and the antimicrobial activity of nisin in different fruit juices. Nisin remained stable in fruit juices (cashew, soursop, peach, mango, passion fruit, orange, guava, and cupuassu) for at least 30 days at room or refrigerated temperature and did not cause any significant alterations in the physico-chemical characteristics of the juices. Besides, nisin favored the preservation of vitamin C content in juices. The antimicrobial activity of nisin was tested against Alicyclobacillus acidoterrestris, Bacillus cereus, Staphylococcus aureus and Listeria monocytogenes in cashew, soursop, peach, and mango juices. Nisin caused a 4-log reduction in viable cells of A. acidoterrestris in soursop, peach, and mango juices after 8h of incubation, and no viable cells were detected in cashew juices. After 24h of incubation in the presence of nisin, no viable cells were detected, independently of the juices. To S. aureus, at 24h of incubation in the presence of nisin, viable cells were only detected in mango juices, representing a 4-log decrease as compared with the control treatment. The number of viable cells of B. cereus at 24h of incubation in the presence of nisin represented at least a 4-log decrease compared to the control treatment. When the antimicrobial activity of nisin was tested against L. monocytogenes in cashew and soursop juices, no reduction in the viable cell number was observed compared to the control treatment after 24h of incubation. Viable cells were four and six times less than in the control treatment, in peach and mango juices respectively. The most sensitive microorganism to nisin was A. acidoterrestris and the least sensitive was L. monocytogenes. Still, a reduction of up to 90% of viable cells was observed in peach and mango juices inoculated with L. monocytogenes. These results indicate that the use of nisin could be an alternative in fruit juice processing. PMID- 26162592 TI - Ability of EDI-2 and EDI-3 to correctly identify patients and subjects at risk for eating disorders. AB - AIMS: The prevention and early recognition of eating disorders (EDs) are important topics in public health. This study aims to compare the efficacy of the Eating Disorder Inventory 2 (EDI-2) with the new version, EDI-3 in recognising patients and identifying subjects at risk for EDs. METHODS: The EDI-2 and EDI-3 were administered to 92 female patients with ED and 265 females from a population at risk for EDs. Experienced psychiatrists in this field held blind interviews with participants by means of the SCID-I to determine the diagnosis. RESULTS: According to the cut-offs suggested by the authors, the EDI-3 correctly identified nearly all of the ED patients (99%), while the EDI-2 divulged less than half (48%). Both versions of the test showed comparable capability to identify participants at risk for EDs but the EDI-3 seemed slightly more reliable than the EDI-2. CONCLUSIONS: The EDI-2 remains a valid and very specific test. However, the new EDI-3 seems to be experimentally superior, because it typifies nearly all patients across the ED span, including those with Binge Eating Disorder and Eating Disorder Not Otherwise Specified. In addition, it appears to be more reliable. PMID- 26162593 TI - Increased prevalence of vegetarianism among women with eating pathology. AB - OBJECTIVE: Prior research has established a link between vegetarianism and disordered eating but has typically sampled vegetarians. This study examined prevalence of and variables related to vegetarianism in three samples with varying severity of eating pathology. METHOD: Sample 1 consisted of female undergraduates who denied history of or current disordered eating (i.e., nonclinical; n=73), or engaged in disordered eating over past month (i.e., subclinical; n=136). Sample 2 included 69 female patients receiving residential treatment at an eating disorder center (i.e., clinical sample). Differences between groups were analyzed using Fisher's exact test. RESULTS: The prevalence of lifetime vegetarianism was lowest in the nonclinical group (6.80%) and highest in the clinical group (34.80%), with the subclinical group falling in between (17.60%). According to Fisher's exact test, all pairwise comparisons between groups were statistically significant (p's<.05). Regarding current vegetarian status, the clinical group was more likely (11.10%) than both other groups to self-identify as current vegetarians. DISCUSSION: Endorsement of vegetarianism was highest among females with severe eating pathology. Future research should use longitudinal data to examine the temporal relationship between these variables, or other underlying factors that may contribute to the co-occurrence of eating pathology and vegetarianism. Clinically, endorsement of vegetarianism may also be an important variable to consider in treatment disordered eating. PMID- 26162594 TI - Optimum sevoflurane concentration for I-gel insertion in unpremedicated children. AB - STUDY OBJECTIVE: End-tidal concentration of sevoflurane for I-gel insertion in children has not been studied. This study was designed to determine the sevoflurane EC50 and EC95 for I-gel placement in children as compared with classic laryngeal mask airway (CLMA) placement. DESIGN: The design was a prospective, randomized controlled study. SETTINGS: The setting was single tertiary care center. PATIENTS: Pediatric subjects of either sex aged 1.5-8 years, weighing 10-20 kg having American Society of Anesthesiologists physical status I/II of undergoing elective cataract surgery were included in the study. INTERVENTION: Induction and maintenance of anesthesia were achieved with sevoflurane and oxygen with preservation of spontaneous breathing. Children were randomly subjected to either I-gel size 2 (group I) or CLMA size 2 (group II) insertion. The target end-tidal sevoflurane concentration (ET SEVO) was maintained for 8-10 minutes before supraglottic airway device was inserted in both the groups. In the first child, the ET SEVO was kept at 2% and was increased or decreased by 0.2% in the next child depending on the previous child's response according to Dixon method. After each supraglottic airway device insertion, child was observed for 1 minute for any "movement" or "no movement." MEASUREMENTS: The measurements were EC50 and EC95 for I-gel and CLMA placement in children. MAIN RESULTS: EC50 and EC95 for group I were 0.94% (0.83%-1.06%) and 1.26% (1.12% 1.66%) and for group II were 1.9% (1.70%-2.1%) and 2.54% (2.24%-3.41%), respectively. CONCLUSION: I-gel insertion in children can be accomplished at nearly half ET SEVO (0.94%) of that required for CLMA insertion (1.9%). PMID- 26162591 TI - Adaptive Immunity in Schizophrenia: Functional Implications of T Cells in the Etiology, Course and Treatment. AB - Schizophrenia is a severe and highly complex neurodevelopmental disorder with an unknown etiopathology. Recently, immunopathogenesis has emerged as one of the most compelling etiological models of schizophrenia. Over the past few years considerable research has been devoted to the role of innate immune responses in schizophrenia. The findings of such studies have helped to conceptualize schizophrenia as a chronic low-grade inflammatory disorder. Although the contribution of adaptive immune responses has also been emphasized, however, the precise role of T cells in the underlying neurobiological pathways of schizophrenia is yet to be ascertained comprehensively. T cells have the ability to infiltrate brain and mediate neuro-immune cross-talk. Conversely, the central nervous system and the neurotransmitters are capable of regulating the immune system. Neurotransmitter like dopamine, implicated widely in schizophrenia risk and progression can modulate the proliferation, trafficking and functions of T cells. Within brain, T cells activate microglia, induce production of pro inflammatory cytokines as well as reactive oxygen species and subsequently lead to neuroinflammation. Importantly, such processes contribute to neuronal injury/death and are gradually being implicated as mediators of neuroprogressive changes in schizophrenia. Antipsychotic drugs, commonly used to treat schizophrenia are also known to affect adaptive immune system; interfere with the differentiation and functions of T cells. This understanding suggests a pivotal role of T cells in the etiology, course and treatment of schizophrenia and forms the basis of this review. PMID- 26162595 TI - Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. AB - Selective serotonin reuptake inhibitors are known to have a range of disorders that are often linked to the endocrine system e.g. hormonal imbalances, breast enlargement, sexual dysfunction, and menstrual cycle disorders. The mechanisms behind most of these disorders are not known in details. In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600 MUM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9 MUM and 3.1 MUM for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine effects of SSRIs may, at least in part, be due to interference with the steroidogenesis. PMID- 26162596 TI - Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4. AB - BACKGROUND: Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor (TLR)-4 mediated mechanism. We hypothesized that effects of parenteral MCTs on immune cells involve TLR-4 signaling and that these effects are modulated by n-3 FA that are present in FO. MATERIALS AND METHODS: To test this hypothesis we assessed effects of addition of various commercially available mixed parenteral lipid emulsions, n 3 FA and of TLR-4 inhibition on MCT-induced human immune cell activation by evaluation of the expression of leukocyte membrane activation markers and reactive oxygen species (ROS) production. RESULTS: All MCT-containing lipid emulsions activated leukocytes by inducing changes in expression of membrane markers and stimulus induced ROS production, whereas MCT-free lipid emulsions lacked this effect. Moreover, addition of n-3 FA to LCT/MCT did not prevent MCT induced immune activation. TLR-4 inhibitors did not distinctly modulate MCT induced changes in immune function. CONCLUSION: Taken together, these findings suggest that leukocyte activation by parenteral MCTs does not involve TLR-4 signaling and is not modulated by n-3 FA in FO-, but is exerted via different signaling pathways. PMID- 26162597 TI - Postmortem quantitative 1.5-T MRI for the differentiation and characterization of serous fluids, blood, CSF, and putrefied CSF. AB - The purpose of the present study was to investigate whether serous fluids, blood, cerebrospinal fluid (CSF), and putrefied CSF can be characterized and differentiated in synthetically calculated magnetic resonance (MR) images based on their quantitative T1, T2, and proton density (PD) values. Images from 55 postmortem short axis cardiac and 31 axial brain 1.5-T MR examinations were quantified using a quantification sequence. Serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF were analyzed for their mean T1, T2, and PD values. Body core temperature was measured during the MRI scans. The fluid-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. In a 3D plot as well as in statistical analysis, the quantitative T1, T2 and PD values of serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF could be well differentiated from each other. The quantitative T1 and T2 values were temperature-dependent. Correction of quantitative values to a temperature of 37 degrees C resulted in significantly better discrimination between all investigated fluid mediums. We conclude that postmortem 1.5-T MR quantification is feasible to discriminate between blood, serous fluids, CSF, and putrefied CSF. This finding provides a basis for the computer-aided diagnosis and detection of fluids and hemorrhages. PMID- 26162599 TI - The stigmatization dilemma in public health policy--the case of MRSA in Denmark. AB - BACKGROUND: Multi-resistant bacteria pose an increasing and significant public health risk. As awareness of the severity of the problem grows, it is likely that it will become the target for a range of public health interventions. Some of these can intentionally or unintentionally lead to stigmatization of groups of citizens. DISCUSSION: The article describes the phenomenon of stigmatization within the health care area by discussing the concept in relation to AIDS and psychiatric diagnosis. It unfolds the ethical aspects of using stigmatization as a public health instrument to affect unwanted behaviours e.g. smoking. Moreover it discusses stigmatization as an unintended albeit expected side effect of public health instruments potentially used to counter the challenge of multi resistant bacteria with particular reference to the Danish case of the growing problems with Methicillin-resistant Staphylococcus aureus (MRSA) within pig production. We argue that using stigmatization as a direct means to achieve public health outcomes is almost always ethically illegitimate. Autonomy and dignity considerations count against it, and the cost-benefit analysis that might by some be taken to outweigh these considerations will be fundamentally uncertain. We further argue that interventions where stigmatization is a side effect need to fulfil requirements of proportionality, and that they may fall prey to 'the stigmatization dilemma', i.e. the dilemma that arises when all policy options are potentially stigmatizing but stigmatize different groups. When this dilemma obtains the decision-maker should choose the intervention that does not lead to permanent stigmatization and that stigmatizes as few as possible, as briefly as possible, and as little as possible. PMID- 26162598 TI - Exploration of SNP variants affecting hair colour prediction in Europeans. AB - DNA profiling is a key tool for forensic analysis; however, current methods identify a suspect either by direct comparison or from DNA database searches. In cases with unidentified suspects, prediction of visible physical traits e.g. pigmentation or hair distribution of the DNA donors can provide important probative information. This study aimed to explore single nucleotide polymorphism (SNP) variants for their effect on hair colour prediction. A discovery panel of 63 SNPs consisting of already established hair colour markers from the HIrisPlex hair colour phenotyping assay as well as additional markers for which associations to human pigmentation traits were previously identified was used to develop multiplex assays based on SNaPshot single-base extension technology. A genotyping study was performed on a range of European populations (n = 605). Hair colour phenotyping was accomplished by matching donor's hair to a graded colour category system of reference shades and photography. Since multiple SNPs in combination contribute in varying degrees to hair colour predictability in Europeans, we aimed to compile a compact marker set that could provide a reliable hair colour inference from the fewest SNPs. The predictive approach developed uses a naive Bayes classifier to provide hair colour assignment probabilities for the SNP profiles of the key SNPs and was embedded into the Snipper online SNP classifier ( http://mathgene.usc.es/snipper/ ). Results indicate that red, blond, brown and black hair colours are predictable with informative probabilities in a high proportion of cases. Our study resulted in the identification of 12 most strongly associated SNPs to hair pigmentation variation in six genes. PMID- 26162600 TI - Evaluation of potential drug- herb interactions among a group of Palestinian patients with chronic diseases. AB - BACKGROUND: The aim of this study was to find the prevalence of potential drug herb interactions in patients with chronic diseases and identify factors associated with these interactions if present. METHOD: The study was a questionnaire based cross-sectional study. It was conducted at a number of governmental primary healthcare centers which include outpatient clinics for chronic diseases between July and November 2013. Patients come to these clinics monthly or bimonthly to receive their medications for their chronic diseases free. The patients in this study were seen at these clinics and their medications were reported from the most recent prescription in their files. RESULTS: A total of 400 patients agreed to be interviewed, 209 (52.3%) were females. The most commonly used medications were metformin, insulin, and enalapril. Among the patients, 237 (59.3%) were using 395 medicinal herbs. The most commonly used herbs were sage, anise and peppermint. In 51 out of the 237 cases (21.5%) at least one potential drug-herb interaction was found. Male patients were more likely to have potential drug-herb interactions. Patients with potential drug herb interactions were older, having a higher mean number of chronic diseases and medications (P-value < 0.05). Only 133 out of 237 (56.1%) users told their prescribers or pharmacists before using medicinal herbs. CONCLUSION: Use of medicinal herbs is a common practice among Palestinian patients attending primary healthcare centers. A substantial proportion failed to disclose to their doctors or pharmacists about herbal products they used, therefore, the physicians and pharmacists are recommended to ask patients about the use of medicinal herbs to avoid any possible negative outcomes. Better counseling and communication between patients and healthcare providers is recommended. PMID- 26162602 TI - Tracking Drug Loading Capacities of Calcium Silicate Hydrate Carrier: A Comparative X-ray Absorption Near Edge Structures Study. AB - Mesoporous spheres of calcium silicate hydrate (MS-CSH) have been prepared by an ultrasonic method. Following an earlier work in which we have revealed the interactions between ibuprofen (IBU) and CSH carriers with different morphologies by X-ray absorption near edge structures (XANES) analysis. In the present investigation, two new drug molecules, alendronate sodium (ALN) and gentamicin sulfate (GS), were incorporated into MS-CSH, and their drug loading capacities (DLCs) were measured using thermogravimetric analysis to establish the relationship between drug-carrier interactions and DLCs. The XANES spectra clearly indicate that acidic functional groups of the drug molecules linked to the active sites (Ca-OH and Si-OH groups) of MS-CSH on the surface by electrostatic interactions. In addition, it is found that the stoichiometric ratio of Ca(2+) ions of CSH carriers and the functional groups of drug molecules may significantly influence the DLCs. PMID- 26162601 TI - Soybean (Glycine max) SWEET gene family: insights through comparative genomics, transcriptome profiling and whole genome re-sequence analysis. AB - BACKGROUND: SWEET (MtN3_saliva) domain proteins, a recently identified group of efflux transporters, play an indispensable role in sugar efflux, phloem loading, plant-pathogen interaction and reproductive tissue development. The SWEET gene family is predominantly studied in Arabidopsis and members of the family are being investigated in rice. To date, no transcriptome or genomics analysis of soybean SWEET genes has been reported. RESULTS: In the present investigation, we explored the evolutionary aspect of the SWEET gene family in diverse plant species including primitive single cell algae to angiosperms with a major emphasis on Glycine max. Evolutionary features showed expansion and duplication of the SWEET gene family in land plants. Homology searches with BLAST tools and Hidden Markov Model-directed sequence alignments identified 52 SWEET genes that were mapped to 15 chromosomes in the soybean genome as tandem duplication events. Soybean SWEET (GmSWEET) genes showed a wide range of expression profiles in different tissues and developmental stages. Analysis of public transcriptome data and expression profiling using quantitative real time PCR (qRT-PCR) showed that a majority of the GmSWEET genes were confined to reproductive tissue development. Several natural genetic variants (non-synonymous SNPs, premature stop codons and haplotype) were identified in the GmSWEET genes using whole genome re-sequencing data analysis of 106 soybean genotypes. A significant association was observed between SNP-haplogroup and seed sucrose content in three gene clusters on chromosome 6. CONCLUSION: Present investigation utilized comparative genomics, transcriptome profiling and whole genome re-sequencing approaches and provided a systematic description of soybean SWEET genes and identified putative candidates with probable roles in the reproductive tissue development. Gene expression profiling at different developmental stages and genomic variation data will aid as an important resource for the soybean research community and can be extremely valuable for understanding sink unloading and enhancing carbohydrate delivery to developing seeds for improving yield. PMID- 26162603 TI - Insight into early-phase trials for lung cancer in the United States. AB - INTRODUCTION: Few data have been published comparing early-phase trials for lung cancer between China and the United States (US). This study was to investigate the differences of phase 1 trials for lung cancer between these two countries. METHODS: In 2014, a cross-sectional survey was conducted to compare phase 1 trials for lung cancer between the Guangdong Lung Cancer Institute (GLCI), the University of Wisconsin Carbone Cancer Center (UWCCC), and the University of Texas MD Anderson Cancer Center (MDACC). RESULTS: We found that the GLCI had a lower percentage of phase 1 lung cancer trials than the MDACC in December 2014 (23.8% [5/21] vs. 59.8% [28/47], P = 0.006) and the UWCCC in September 2014 (16.7% [3/18] vs. 34.8% [8/23], P = 0.345). Descriptive analyses were performed for early-phase trials conducted by the Cancer Therapy Evaluation Program at the National Cancer Institute (CTEP/NCI), the MDACC, and the Chinese Thoracic Oncology Group (CTONG). There were 149 ongoing early-phase trials in the Department of Investigational Cancer Therapeutics (Phase 1 program) at the MDACC in October 2014. In contrast, no phase 1 trials had been initiated by the CTONG since its establishment in 2007. CONCLUSIONS: These data suggest that a significantly higher percentage of phase 1 trials for lung cancer were conducted in the US than in China. Early-phase oncology trials with robust preclinical data had a higher chance of being approved by the Investigational Drug Branch at the CTEP/NCI. Given the importance of early-phase oncology trials in developing innovative cancer medicines, such studies should be highly encouraged and strategically funded in China. PMID- 26162604 TI - Response to: the nature of evidence for and against epigenetic inheritance. AB - We thank Dr. Nadeau for his interest in our work. Dr. Nadeau has raised concerns about the experimental approach (mouse strains, route of administration, lack of phenotypic assessment) and about the validity of our conclusions. We will respond to each of these concerns point-by point.Please see related article: www.dx.doi.org/10.1186/s13059-015-0709-y. PMID- 26162606 TI - Smoking cigarettes may increase risk of schizophrenia, study shows. PMID- 26162605 TI - Simultaneous exposure to multiple heavy metals and glyphosate may contribute to Sri Lankan agricultural nephropathy. AB - BACKGROUND: Sri Lankan Agricultural Nephropathy (SAN), a new form of chronic kidney disease among paddy farmers was first reported in 1994. It has now become the most debilitating public health issue in the dry zone of Sri Lanka. Previous studies showed SAN is a tubulo-interstitial type nephropathy and exposure to arsenic and cadmium may play a role in pathogenesis of the disease. METHODS: Urine samples of patients with SAN (N = 10) from Padavi-Sripura, a disease endemic area, and from two sets of controls, one from healthy participants (N = 10) from the same endemic area and the other from a non-endemic area (N = 10; Colombo district) were analyzed for 19 heavy metals and for the presence of the pesticide- glyphosate. RESULTS: In both cases and the controls who live in the endemic region, median concentrations of urinary Sb, As, Cd, Co, Pb, Mn, Ni, Ti and V exceed the reference range. With the exception of Mo in patients and Al, Cu, Mo, Se, Ti and Zn in endemic controls, creatinine adjusted values of urinary heavy metals and glyphosate were significantly higher when compared to non endemic controls. Creatinine unadjusted values were significant higher for 14 of the 20 chemicals studied in endemic controls and 7 in patients, compared to non endemic controls. The highest urinary glyphosate concentration was recorded in SAN patients (range 61.0-195.1 MUg/g creatinine). CONCLUSIONS: People in disease endemic area exposed to multiple heavy metals and glyphosate. Results are supportive of toxicological origin of SAN that is confined to specific geographical areas. Although we could not localize a single nephrotoxin as the culprit for SAN, multiple heavy metals and glyphosates may play a role in the pathogenesis. Heavy metals excessively present in the urine samples of patients with SAN are capable of causing damage to kidneys. Synergistic effects of multiple heavy metals and agrochemicals may be nephrotoxic. PMID- 26162608 TI - Cancer incidence varies widely across England, figures show. PMID- 26162607 TI - Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper. AB - Neuromedin U (NMU) and neuromedin S (NMS) play inhibitory roles in the regulation of food intake and energy homeostasis in mammals. However, their functions are not clearly established in teleost fish. In the present study, nmu and nms homologs were identified in several fish species. Subsequently, their cDNA sequences were cloned from the orange-spotted grouper (Epinephelus coioides). Sequence analysis showed that the orange-spotted grouper Nmu proprotein contains a 21-amino acid mature Nmu peptide (Nmu-21). The Nms proprotein lost the typical mature Nms peptide, but it retains a putative 34-amino acid peptide (Nmsrp). In situ hybridization revealed that nmu- and nms-expressing cells are mainly localized in the hypothalamic regions associated with appetite regulation. Food deprivation decreased the hypothalamic nmu mRNA levels but induced an increase of nms mRNA levels. Periprandial expression analysis showed that hypothalamic expression of nmu increased significantly at 3 h post-feeding, while nms expression was elevated at the normal feeding time. I.p. injection of synthetic Nmu-21 peptide suppressed the hypothalamic neuropeptide y (npy) expression, while Nmsrp administration significantly increased the expression of npy and orexin in orange-spotted grouper. Furthermore, the mRNA levels of LH beta subunit (lhbeta) and gh in the pituitary were significantly down-regulated after Nmu-21 peptide administration, while Nmsrp was able to significantly stimulate the expression of FSH beta subunit (fshbeta), prolactin (prl), and somatolaction (sl). Our results indicate that nmu and nms possess distinct neuroendocrine functions and pituitary functions in the orange spotted grouper. PMID- 26162610 TI - Therapeutic Effects and Mechanisms of Action of Rifaximin in Gastrointestinal Diseases. AB - Emerging preclinical and clinic evidence described herein suggests that the mechanism of action of rifaximin is not restricted to direct antibacterial effects within the gastrointestinal tract. Data from this study were derived from general and clinical trial-specific PubMed searches of English-language articles on rifaximin available through December 3, 2014. Search terms included rifaximin alone and in combination (using the Boolean operation "AND") with travelers' diarrhea, hepatic encephalopathy, liver cirrhosis, irritable bowel syndrome, inflammatory bowel disease, and Crohn's disease. Rifaximin appears to reduce bacterial virulence and pathogenicity by inhibiting bacterial translocation across the gastrointestinal epithelial lining. Rifaximin was shown to decrease bacterial adherence to epithelial cells and subsequent internalization in a bacteria- and cell type-specific manner, without an alteration in bacterial counts, but with a down-regulation in epithelial proinflammatory cytokine expression. Rifaximin also appears to modulate gut-immune signaling. In animal models of inflammatory bowel disease, rifaximin produced therapeutic effects by activating the pregnane X receptor and thereby reducing levels of the proinflammatory transcription factor nuclear factor kappaB. Therefore, for a given disease state, rifaximin may act through several mechanisms of action to exert its therapeutic effects. Clinically, rifaximin 600 mg/d significantly reduced symptoms of travelers' diarrhea (eg, time to last unformed stool vs placebo [32.0 hours vs 65.5 hours, respectively; P=.001]). For the prevention of hepatic encephalopathy recurrence, data indicate that treating 4 patients with rifaximin 1100 mg/d for 6 months would prevent 1 episode of hepatic encephalopathy. For diarrhea-predominant irritable bowel syndrome, a significantly greater percentage (40.7%) of patients treated with rifaximin 1650 mg/d for 2 weeks experienced adequate global irritable bowel syndrome symptom relief vs placebo (31.7%; P<.001). Rifaximin may be best described as a gut microenvironment modulator with cytoprotection properties, and further studies are needed to determine whether these putative mechanisms of action play a direct role in clinical outcomes. PMID- 26162611 TI - A Man's (Precarious) Place: Men's Experienced Threat and Self-Assertive Reactions to Female Superiors. AB - Across three studies, we investigate men's reactions to women in superior roles. Drawing from precarious manhood theory, we hypothesize that when a woman occupies a superior organizational role, men in subordinate positions experience threat, which leads them to behave more assertively toward her and advocate for themselves. In Studies 1 and 2, we demonstrate that men feel more threatened (relative to women) by women in superior roles (relative to men in superior roles) and, as a result, engage in more assertive behaviors toward these women. In Study 3, we investigate a boundary condition to this effect and demonstrate that a woman in a superior role who displays qualities associated with administrative agency (e.g., directness, proactivity) rather than ambitious agency (e.g., self-promotion, power-seeking) elicits less assertive behavior from men. We conclude by discussing implications as well as directions for future research. PMID- 26162609 TI - Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial. AB - BACKGROUND: Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. PATIENTS AND METHODS: We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. RESULTS: A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). CONCLUSION: This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit. PMID- 26162613 TI - Sensitivity of PPI analysis to differences in noise reduction strategies. AB - BACKGROUND: In some fields of fMRI data analysis, using correct methods for dealing with noise is crucial for achieving meaningful results. This paper provides a quantitative assessment of the effects of different preprocessing and noise filtering strategies on psychophysiological interactions (PPI) methods for analyzing fMRI data where noise management has not yet been established. METHODS: Both real and simulated fMRI data were used to assess these effects. Four regions of interest (ROIs) were chosen for the PPI analysis on the basis of their engagement during two tasks. PPI analysis was performed for 32 different preprocessing and analysis settings, which included data filtering with RETROICOR or no such filtering; different filtering of the ROI "seed" signal with a nuisance data-driven time series; and the involvement of these data-driven time series in the subsequent PPI GLM analysis. The extent of the statistically significant results was quantified at the group level using simple descriptive statistics. Simulated data were generated to assess statistical improvement of different filtering strategies. RESULTS: We observed that different approaches for dealing with noise in PPI analysis yield differing results in real data. In simulated data, we found RETROICOR, seed signal filtering and the addition of data-driven covariates to the PPI design matrix significantly improves results. CONCLUSIONS: We recommend the use of RETROICOR, and data-driven filtering of the whole data, or alternatively, seed signal filtering with data-driven signals and the addition of data-driven covariates to the PPI design matrix. PMID- 26162614 TI - EMDLAB: A toolbox for analysis of single-trial EEG dynamics using empirical mode decomposition. AB - BACKGROUND: Empirical mode decomposition (EMD) is an empirical data decomposition technique. Recently there is growing interest in applying EMD in the biomedical field. NEW METHOD: EMDLAB is an extensible plug-in for the EEGLAB toolbox, which is an open software environment for electrophysiological data analysis. RESULTS: EMDLAB can be used to perform, easily and effectively, four common types of EMD: plain EMD, ensemble EMD (EEMD), weighted sliding EMD (wSEMD) and multivariate EMD (MEMD) on EEG data. In addition, EMDLAB is a user-friendly toolbox and closely implemented in the EEGLAB toolbox. COMPARISON WITH EXISTING METHODS: EMDLAB gains an advantage over other open-source toolboxes by exploiting the advantageous visualization capabilities of EEGLAB for extracted intrinsic mode functions (IMFs) and Event-Related Modes (ERMs) of the signal. CONCLUSIONS: EMDLAB is a reliable, efficient, and automated solution for extracting and visualizing the extracted IMFs and ERMs by EMD algorithms in EEG study. PMID- 26162615 TI - Impaired recognition of body expressions in the behavioral variant of frontotemporal dementia. AB - Progressive deterioration of social cognition and emotion processing are core symptoms of the behavioral variant of frontotemporal dementia (bvFTD). Here we investigate whether bvFTD is also associated with impaired recognition of static (Experiment 1) and dynamic (Experiment 2) bodily expressions. In addition, we compared body expression processing with processing of static (Experiment 3) and dynamic (Experiment 4) facial expressions, as well as with face identity processing (Experiment 5). The results reveal that bvFTD is associated with impaired recognition of static and dynamic bodily and facial expressions, while identity processing was intact. No differential impairments were observed regarding motion (static vs. dynamic) or category (body vs. face). Within the bvFTD group, we observed a significant partial correlation between body and face expression recognition, when controlling for performance on the identity task. Voxel-Based Morphometry (VBM) analysis revealed that body emotion recognition was positively associated with gray matter volume in a region of the inferior frontal gyrus (pars orbitalis/triangularis). The results are in line with a supramodal emotion recognition deficit in bvFTD. PMID- 26162616 TI - Second language as a compensatory resource for maintaining verbal fluency in bilingual immigrants with schizophrenia. AB - BACKGROUND AND OBJECTIVES: Due to the large migrations over the past three decades, large numbers of individuals with schizophrenia are learning a second language and being seen in clinics in that second language. We conducted within subject comparisons to clarify the contribution of clinical, linguistic and bilingual features in the first and second languages of bilinguals with schizophrenia. METHODS: Ten bilingual Russian(L1) and Hebrew(L2) proficient patients, who developed clinical schizophrenia after achieving proficiency in both languages, were selected from 60 candidates referred for the study; they were resident in Israel 7-32 years with 3-10 years from immigration to diagnosis. Clinical, linguistic and fluency markers were coded in transcripts of clinical interviews. RESULTS: There was a trend toward more verbal productivity in the first language (L1) than the second language (L2). Clinical speech markers associated with thought disorder and cognitive impairment (blocking and topic shift) were similar in both languages. Among linguistic markers of schizophrenia, Incomplete syntax and Speech role reference were significantly more frequent in L2 than L1; Lexical repetition and Unclear reference demonstrated a trend in the same direction. For fluency phenomena, Discourse markers were more prevalent in L1 than L2, and Codeswitching was similar across languages, showing that the patients were attuned to the socio-pragmatics of language use. CONCLUSIONS: More frequent linguistic markers of schizophrenia in L2 show more impairment in the syntactic/semantic components of language, reflecting greater thought and cognitive dysfunction. Patients are well able to acquire a second language. Nevertheless, schizophrenia finds expression in that language. Finally, more frequent fluency markers in L1 suggests motivation to maintain fluency, evidenced in particular by codeswitched L2 lexical items, a compensatory resource. PMID- 26162617 TI - Visual cortex activity predicts subjective experience after reading books with colored letters. AB - One of the most astonishing properties of synesthesia is that the evoked concurrent experiences are perceptual. Is it possible to acquire similar effects after learning cross-modal associations that resemble synesthetic mappings? In this study, we examine whether brain activation in early visual areas can be directly related to letter-color associations acquired by training. Non synesthetes read specially prepared books with colored letters for several weeks and were scanned using functional magnetic resonance imaging. If the acquired letter-color associations were visual in nature, then brain activation in visual cortex while viewing the trained black letters (compared to untrained black letters) should predict the strength of the associations, the quality of the color experience, or the vividness of visual mental imagery. Results showed that training-related activation of area V4 was correlated with differences in reported subjective color experience. Trainees who were classified as having stronger 'associator' types of color experiences also had more negative activation for trained compared to untrained achromatic letters in area V4. In contrast, the strength of the acquired associations (measured as the Stroop effect) was not reliably reflected in visual cortex activity. The reported vividness of visual mental imagery was related to veridical color activation in early visual cortex, but not to the acquired color associations. We show for the first time that subjective experience related to a synesthesia-training paradigm was reflected in visual brain activation. PMID- 26162618 TI - Pediatric occult methanol intoxication with hyperammonemia. PMID- 26162619 TI - A peculiar case of Lance-Adams syndrome. PMID- 26162620 TI - The perfect storm: copper deficiency presenting as progressive peripheral neuropathy. PMID- 26162621 TI - Confirmatory factor analysis of the Autonomy over Tobacco Scale (AUTOS) in adults. AB - INTRODUCTION: The Autonomy over Tobacco Scale (AUTOS), a 12-item self administered questionnaire, was designed to measure autonomy in three correlated lower-order symptom domains: withdrawal, psychological dependence, and cue induced craving. The factor structure of the AUTOS remains an open question; confirmatory analyses in adolescents supported the hierarchical structure, while exploratory analyses in adolescents and adults yield single-factor solutions. Here we seek to determine whether the hypothesized hierarchical structure is valid in adult smokers. METHODS: The AUTOS was administered to two independent convenience samples of adult current smokers: a calibration sample recruited in the US for online studies, and a confirmation sample drawn from the prospective Nicotine Dependence in Teens study in Montreal. We tested competing hierarchical and single-factor models using the robust weighted least-squares (WLSMV) estimation method. RESULTS: A single-factor model that allowed correlated error variances between theoretically related items fit well in the calibration sample (n = 434), chi(2)SB(52) = 165.71; chi(2)/df = 3.19; SRMR = 0.03; CFI = 0.96; NNFI = 0.95; RMSEA = 0.07 (95% CI: 0.06, 0.08). Reliability of the single factor was high (omegaB = 0.92) and construct validity was adequate. In the confirmation sample (n = 335), a similar model fit well:chi(2)SB(53) = 126.94; chi(2)/df = 2.44; SRMR = 0.04; CFI = 0.95; NNFI = 0.93; RMSEA = 0.07 (95% CI: 0.05, 0.08). Reliability of the single factor was again high (omegaB = 0.92) and construct validity was adequate. CONCLUSION: The AUTOS is unidimensional in adult smokers. PMID- 26162622 TI - The Effects of Lithium Administration on Oxidant/Antioxidant Status in Rats: Biochemical and Histomorphological Evaluations. AB - Present study was planned to determine possible dose-dependent effects of lithium (Li) on oxidant-antioxidant status and histomorphological changes in liver and kidney tissues. For this purpose, twenty-four Wistar male rats were equally divided into three groups: the rats in group I served as controls, drinking tap water without lithium. Groups II and III received 0.1 and 0.2 % lithium carbonate (Li2CO3) through their drinking water, respectively, for 30 days. At the end of the experimental period, lithium concentrations, levels of malondialdehyde (MDA) and glutathione (GSH) and superoxide dismutase (SOD) activities were measured in considered tissues. Histomorphological study was also performed on liver and kidney tissues. Compared to controls, MDA was significantly higher but GSH level lower in groups II and III. SOD activity was higher in group III, but no difference was determined in group II in liver tissue. In kidney tissue, there was no difference determined in MDA and GSH levels between control and experimental groups but SOD activity in groups II and III was significantly higher. In histologic sections of both experimental liver and kidney tissues, specific degenerations were observed. The results of the present study show that treatment with lithium carbonate may result in liver and kidney tissue abnormalities and oxidative damage. PMID- 26162623 TI - Selenium Supplementation of Amaranth Sprouts Influences Betacyanin Content and Improves Anti-Inflammatory Properties via NFkappaB in Murine RAW 264.7 Macrophages. AB - Sprouts contain potent compounds which while influencing crucial transduction pathways in cell reveal anti-inflammatory and anticancer activities. In this study, we report the biological activity for seeds and colourful sprouts of four types of edible amaranth, as amaranth has recently attracted interest due to its appreciable nutritional value. MTT assay conducted for the amaranth seeds and sprouts did not show any adverse effect on the viability of murine RAW 264.7 cells. As amaranth accumulates selenium, the sprouts were supplemented with this trace element (10 mg/L; 15 mg/L Se as sodium selenite) while growing. Selenium concentration in sprouts was observed to be significantly correlated with betacyanins content of the tested species. The amounts of Se and betacyanins in sprouts varied for various Amaranth species. In the present study, Amaranthus cruentus sprouts with the highest betacyanins (19.30 +/- 0.57-28.85 +/- 2.23 mg of amaranthin/100 g of fresh weight) and high total selenium (22.51 +/- 1.57 1044.75 +/- 73.08 MUg/L in methanol extracts) content prevented NFkappaB translocation to the cell nucleus and subsequently exerted an anti-inflammatory effect by significant decreasing inflammatory interleukin 6 production (587.3 +/- 34.2-710.0 +/- 88.1 pg/mL) in the cell culture of activated RAW 264.7 macrophages (vs LPS control 1520 +/- 114 pg/mL). PMID- 26162624 TI - The Content of Copper and Molybdenum in the Liver, Kidneys, and Skeletal Muscles of Elk (Alces alces) from North-Eastern Poland. AB - The aim of the study was to evaluate the content of Cu and Mo in the liver, kidneys, and skeletal muscles of elks from north-eastern Poland. The investigation material comprised samples obtained in 2010 from 35 animals. Animals were grouped according to age (elks up to 2 years and over than 3 years). The metal concentrations were determined using coupled plasma-mass spectrometry (ICP-MS) method. The mean Cu concentrations in the liver, kidneys, and skeletal muscles were 23.08, 5.03, and 2.36 mg?kg(-1) wet weight, respectively. The mean Mo content in the examined samples was as follows: 0.92, 0.42, and 0.05 mg?kg(-1) wet weight (w.w.) in the liver, kidneys, and muscles. In the analysis of correlation between the Cu and Mo levels in particular organs, the presence of significant dependence (p <= 0.05) was observed in the liver of animals studied. The mean Cu content in the liver of animals studied is lower compared with data reported from Sweden, Russia, and North America. Concentrations of Cu and Mo in the kidneys and skeletal muscles of Polish elks are similar to data noted in healthy animals from Scandinavian region. The results suggest that elks from north-eastern Poland may be threatened by primary Cu deficiency. PMID- 26162626 TI - Autophagosomes and lipid droplets: no longer just chewing the fat. PMID- 26162625 TI - Lipid droplets and their component triglycerides and steryl esters regulate autophagosome biogenesis. AB - Autophagy is a major catabolic process responsible for the delivery of proteins and organelles to the lysosome/vacuole for degradation. Malfunction of this pathway has been implicated in numerous pathological conditions. Different organelles have been found to contribute to the formation of autophagosomes, but the exact mechanism mediating this process remains obscure. Here, we show that lipid droplets (LDs) are important for the regulation of starvation-induced autophagy. Deletion of Dga1 and Lro1 enzymes responsible for triacylglycerol (TAG) synthesis, or of Are1 and Are2 enzymes responsible for the synthesis of steryl esters (STE), results in the inhibition of autophagy. Moreover, we identified the STE hydrolase Yeh1 and the TAG lipase Ayr1 as well as the lipase/hydrolase Ldh1 as essential for autophagy. Finally, we provide evidence that the ER-LD contact-site proteins Ice2 and Ldb16 regulate autophagy. Our study thus highlights the importance of lipid droplet dynamics for the autophagic process under nitrogen starvation. PMID- 26162627 TI - What do the general population know, believe and feel about individuals with autism and schizophrenia: Results from a comparative survey in Denmark. AB - Few studies investigate what members of the general population know about individuals with autism. Only one study has previously investigated how beliefs about autism differ from those about other psychiatric disorders. This study surveyed a convenience sample of the general adult population, within the Northern Region of Denmark, about their knowledge, attitudes and beliefs about individuals with autism and schizophrenia. The respondents (N = 440) possessed basic knowledge and were able to differentiate between the two disorders. Schizophrenia was associated with perceived danger (32.8%), while autism was associated with high intelligence (40.1%) and creativity (27.3%). Respondents were more positive towards interacting with individuals with autism (p < 0.001), but desire for social distancing was pronounced for both disorders in more intimate relationships. Significantly, more respondents reported that they would find it difficult and feel ashamed with regard to being diagnosed with schizophrenia (p < 0.001). Conversely, respondents significantly reported being more likely to elaborate on their diagnosis of autism to their colleagues (p < 0.001). Perceived dangerousness decreased the willingness for social interactions, while knowing someone with autism or schizophrenia increased the willingness to socially interact. Misconceptions and stigma must be addressed in order to minimize the social stigma and rejection associated with these disorders and ultimately improve the quality of life and psychological well-being of affected individuals and their families. PMID- 26162628 TI - A description of medical conditions in adults with autism spectrum disorder: A follow-up of the 1980s Utah/UCLA Autism Epidemiologic Study. AB - This study describes medical conditions experienced by a population-based cohort of adults with autism spectrum disorder whose significant developmental concerns were apparent during childhood. As part of a 25-year outcome study of autism spectrum disorder in adulthood, medical histories were collected on 92 participants (N = 69 males) who were first ascertained as children in the mid 1980s, 11 of whom were deceased at the time of follow-up. Questionnaires queried medical symptoms, disorders, hospitalizations, surgeries, and medication use. Median age at follow-up was 36 years (range: 23.5-50.5 years), and intellectual disability co-occurred in 62%. The most common medical conditions were seizures, obesity, insomnia, and constipation. The median number of medical conditions per person was 11. Increased medical comorbidity was associated with female gender (p = 0.01) and obesity (p = 0.03), but not intellectual disability (p = 0.79). Adults in this cohort of autism spectrum disorder first ascertained in the 1980s experience a high number of chronic medical conditions, regardless of intellectual ability. Understanding of these conditions commonly experienced should direct community-based and medical primary care for this population. PMID- 26162629 TI - Elimination of formate production in Clostridium thermocellum. AB - The ability of Clostridium thermocellum to rapidly degrade cellulose and ferment resulting hydrolysis products into ethanol makes it a promising platform organism for cellulosic biofuel production via consolidated bioprocessing. Currently, however, ethanol yield is far below theoretical maximum due to branched product pathways that divert carbon and electrons towards formate, H2, lactate, acetate, and secreted amino acids. To redirect carbon and electron flux away from formate, genes encoding pyruvate:formate lyase (pflB) and PFL-activating enzyme (pflA) were deleted. Formate production in the resulting Deltapfl strain was eliminated and acetate production decreased by 50 % on both complex and defined medium. The growth rate of the Deltapfl strain decreased by 2.9-fold on defined medium and biphasic growth was observed on complex medium. Supplementation of defined medium with 2 mM formate restored Deltapfl growth rate to 80 % of the parent strain. The role of pfl in metabolic engineering strategies and C1 metabolism is discussed. PMID- 26162630 TI - Scalable temperature induced stress for the large-scale production of functionalized Bifidobacteria. AB - The application of sub-lethal stresses is known to be an efficient strategy to enhance survival of probiotic bacteria during drying processes. In this context, we previously showed that the application of heat stress upon the entry into stationary phase increased significantly the viability of Bifidobacterium bifidum. However, this heat shock has been considered only in small-scale bioreactor and no information is available for a possible scaling-up strategy. Five different operating scales (0.2, 2, 20, 200 and 2000 L) have thus been tested and the results showed that the viability of B. bifidum increases from 3.15 to 6.57 folds, depending on the scale considered. Our observations pointed out the fact that the heat stress procedure is scalable according to the main outcome, i.e., increases in cell viability, but other factors have to be taken into account. Among these factors, dissolved carbon dioxide seems to play a significant role, since it explains the differences observed between the test performed at laboratory scale and in industrial conditions. PMID- 26162631 TI - Detection of expanded-spectrum beta-lactamases in Gram-negative bacteria in the 21st century. AB - Emerging beta-lactamase-producing-bacteria (ESBL, AmpC and carbapenemases) have become a serious problem in our community due to their startling spread worldwide and their ability to cause infections which are difficult to treat. Diagnosis of these beta-lactamases is of clinical and epidemiological interest. Over the past 10 years, several methods have been developed aiming to rapidly detect these emerging enzymes, thus preventing their rapid spread. In this review, we describe the range of screening and detection methods (phenotypic, molecular and other) for detecting these beta-lactamases but also whole genome sequencing as a tool for detecting the genes encoding these enzymes. PMID- 26162632 TI - Improvement in patient-reported outcomes after rituximab in rheumatoid arthritis patients: An open-label assessment of 175 patients. AB - OBJECTIVE: Patient-reported outcomes (PROs) reflect treatment efficacy from the patients' perspective. The objective was to assess PROs improvement with rituximab in rheumatoid arthritis. METHODS: Patients with long-standing rheumatoid arthritis received rituximab 1000mg twice at 2 weeks interval, and were assessed over 6 months. PROs including physical PROs (pain, functional assessment, physical quality of life) and mental or mixed aspects (fatigue, sleep and mental quality of life) were assessed. Standardized response means were calculated. Early improvement in PROs was used to predict EULAR response at 6 months. RESULTS: For the 175 patients (mean age 54.6+/-10.6 years, mean disease duration 12.9+/-9.3 years), the plateau of efficacy of rituximab on PROs was reached at week 12, and the effect was more prominent on physical PROs (e.g., pain standardized response means -0.75 [95% confidence interval -0.91; -0.60]), than on sleep (-0.43; [-0.56; -0.29]). It was not possible to accurately predict 6-month EULAR response by early improvement in PROs. CONCLUSION: Rituximab was effective on PROs with an early effect. PROs reflecting physical aspects were more modulated by this biologic than other PROs (fatigue, sleep or mental quality of life). Links between sleep difficulties, fatigue and RA should be further studied. PMID- 26162633 TI - Reply to the comment of Brinster et al. "Acquired hemophilia, rheumatoid arthritis, and TNFalpha antagonists". PMID- 26162634 TI - Spondyloarthritis: A concept or a disease? PMID- 26162635 TI - Efficacy of Tocilizumab in the treatment of Eosinophilic fasciitis: Report of one case. AB - A 43-year-old man was diagnosed with an Eosinophilic fasciitis with cutaneous and articular involvement. The patient experienced an early response with high-dose corticosteroids achieving a global remission of disease. Nevertheless, during the steroids tapering phase, he presented a new flare and subsequently developed a corticosteroid refractory disease. The addition of Methotrexate in monotherapy then associated with an anti-tumor necrosis factor agent did not show any additional benefit. Therefore Tocilizumab, a humanized monoclonal antibody against the interleukin-6 receptor, was initiated achieving an immediate response that persists after 36 months of follow-up. The use of this biological agent allows prednisone withdrawal at 3 months and remission of both articular and cutaneous manifestations at 6 months. This report describes for the first time the efficacy of an anti interleukin-6 agent in Eosinophilic fasciitis treatment. PMID- 26162636 TI - Does platelet-rich plasma have a role in the treatment of osteoarthritis? AB - Platelet-rich plasma (PRP) has been generating considerable attention as an intra articular treatment to alleviate the symptoms of osteoarthritis. Activated platelets release a host of soluble mediators such as growth factors and cytokines, thereby inducing complex interactions that vary across tissues within the joint. In vivo, PRP may promote chondrocyte proliferation and differentiation. The available data are somewhat conflicting regarding potential effects on synovial cells and angiogenesis modulation. PRP probably exerts an early anti-inflammatory effect, which may be chiefly mediated by inhibition of the NF-kappaB pathway, a hypothesis that requires confirmation by proof-of concept studies. It is far too early to draw conclusions about the efficacy of PRP as a treatment for hip osteoarthritis. The only randomized trial versus hyaluronic acid showed no significant difference in effects, and no placebo controlled trials are available. Most of the randomized trials in knee osteoarthritis support a slightly greater effect in alleviating the symptoms compared to visco-supplementation, most notably at the early stages of the disease, although only medium-term data are available. Many uncertainties remain, however, regarding the best administration regimen. Serious adverse effects, including infections and allergies, seem rare, although post-injection pain is more common than with other intra-articular treatments for osteoarthritis. PMID- 26162637 TI - [Catheter-based closure of paravalvular leaks: "Plug the hole"]. AB - Paravalvular leak (PVL) is a relatively rare, but serious complication occurring in up to 10% of patients after prosthetic aortic valve replacement and in up to 17% of patients after prosthetic mitral valve replacement. Up to 5% of patients will present with symptoms of congestive heart failure or mechanical haemolytic anaemia due to PVL and need further surgical or interventional treatment. Surgical repair is often technically challenging and carries a high mortality and morbidity risk. Catheter-based closure of PVL has emerged as an alternative approach especially for patients with relevant comorbidities at high surgical risk. Interventional closure of PVL is a complex procedure, which needs to be performed by an experienced team of interventional cardiologist, echocardiographer and anesthesiologist. To date available clinical results are promising showing low complication rates and high technical or clinical success rates of catheter-based closure of PVL (60-90%). Compared to surgical closure of PVL lower mortality rates (30-days mortality rate: 4,6%) have been documented in patients treated by catheter-based closure of PVL in clinical practice. Therefore interventional closure seems to be a promising option, which need to be discussed with every symptomatic patient suffering from PVL prior to therapeutical decision making. To date only sparse clinical data is available regarding indication and clinical outcome of patients undergoing catheter-based PVL in clinical practice. Therefore interventional closure of PVL should be limited to experienced interventional cardiologist at present. All patients treated should further be enrolled into a clinical registry to evaluate the safety and efficacy of catheter based closure of PVL in clinical practice. PMID- 26162638 TI - Erratum to: Left ventricular pseudoaneurysm after mitral valve replacement: Review of pseudoaneurysms late after mitral valve replacement. PMID- 26162639 TI - Psychometric properties and validation of Portuguese version of Ages & Stages Questionnaires (3rd edition): 9, 18 and 30 Questionnaires. AB - BACKGROUND: The essential underlying foundations of Early Intervention (EI), in which parents/family play a critical role in their child's development, leads us to conclude that their contribution assessing early detection of problems is fundamental. The Ages & Stages Questionnaires (ASQ) is a standardized screening instrument that has been successfully studied in different countries and cultures. AIMS: Translate and study the psychometrics proprieties of the Portuguese version of the 9, 18 and 30month questionnaires of the Ages and Stages Questionnaires, 3rd edition (ASQ-3). STUDY DESIGN: Cross-sectional study. SUBJECTS: Validity and reliability were studied in a sample of 234 parents of children within 9, 18 and 30months. RESULTS: The results indicated that the questionnaires had good internal consistency, strong agreement between observers and between observations with two weeks interval, and strong Pearson product moment correlation coefficients between the overall and the total for each domain. The cutoff points (i.e. 2 standard deviations below the mean domain score), that identifies children who should receive further referral for more comprehensive assessment, were close to those determined in the original ASQ-3 psychometric studies. Cronbach's alpha ranging from .42 to .70 and Pearson's r values varies from .22 to .60. CONCLUSIONS: Although some weaknesses were noted in psychometric qualities analysis, it can be concluded that the ASQ-PT of 9, 18 and 30months of age fulfills the requirements of a screening tool validated for the Portuguese population. PRACTICE IMPLICATIONS: To allow the early identification of children with developmental problems. PMID- 26162640 TI - Estimating under-reporting of road crash injuries to police using multiple linked data collections. AB - The reliance on police data for the counting of road crash injuries can be problematic, as it is well known that not all road crash injuries are reported to police which under-estimates the overall burden of road crash injuries. The aim of this study was to use multiple linked data sources to estimate the extent of under-reporting of road crash injuries to police in the Australian state of Queensland. Data from the Queensland Road Crash Database (QRCD), the Queensland Hospital Admitted Patients Data Collection (QHAPDC), Emergency Department Information System (EDIS), and the Queensland Injury Surveillance Unit (QISU) for the year 2009 were linked. The completeness of road crash cases reported to police was examined via discordance rates between the police data (QRCD) and the hospital data collections. In addition, the potential bias of this discordance (under-reporting) was assessed based on gender, age, road user group, and regional location. Results showed that the level of under-reporting varied depending on the data set with which the police data was compared. When all hospital data collections are examined together the estimated population of road crash injuries was approximately 28,000, with around two-thirds not linking to any record in the police data. The results also showed that the under-reporting was more likely for motorcyclists, cyclists, males, young people, and injuries occurring in Remote and Inner Regional areas. These results have important implications for road safety research and policy in terms of: prioritising funding and resources; targeting road safety interventions into areas of higher risk; and estimating the burden of road crash injuries. PMID- 26162641 TI - Safety effects of exclusive and concurrent signal phasing for pedestrian crossing. AB - This paper describes the estimation of pedestrian crash count and vehicle interaction severity prediction models for a sample of signalized intersections in Connecticut with either concurrent or exclusive pedestrian phasing. With concurrent phasing, pedestrians cross at the same time as motor vehicle traffic in the same direction receives a green phase, while with exclusive phasing, pedestrians cross during their own phase when all motor vehicle traffic on all approaches is stopped. Pedestrians crossing at each intersection were observed and classified according to the severity of interactions with motor vehicles. Observation intersections were selected to represent both types of signal phasing while controlling for other physical characteristics. In the nonlinear mixed models for interaction severity, pedestrians crossing on the walk signal at an exclusive signal experienced lower interaction severity compared to those crossing on the green light with concurrent phasing; however, pedestrians crossing on a green light where an exclusive phase was available experienced higher interaction severity. Intersections with concurrent phasing have fewer total pedestrian crashes than those with exclusive phasing but more crashes at higher severity levels. It is recommended that exclusive pedestrian phasing only be used at locations where pedestrians are more likely to comply. PMID- 26162642 TI - First Isolation of Azole-Resistant Cryptococcus neoformans from Feline Cryptococcosis. AB - We report here, to the best of our knowledge, the first description of an in vitro fluconazole (FLZ)-resistant Cryptococcus neoformans var. grubii from a case of feline cryptococcosis. In vitro testing demonstrated that this isolate was resistant to FLZ (minimum inhibitory concentration, MIC, of 128 MUg/ml) but remained susceptible to amphotericin B (0.064 ug/ml), itraconazole (0.38 ug/ml), voriconazole (0.023 ug/ml), and posaconazole (0.125 ug/ml). The predicted amino acid sequence of the lanosterol 14-alpha demethylase (ERG11) protein in the isolate was identical to that of the C. neoformans var. grubii reference strain, indicating that resistance was not mediated by mutation of the target gene's open reading frame. The RT-qPCR analysis for ERG11 and ATP-binding cassette (ABC) transporter-encoding gene (AFR1) indicated that the isolate increased transcription factor function of ERG11 and AFR1 than that of FLZ-susceptive strains. This observation, in combination with the lack of resistance to other azoles (that is, lack of crossresistance), suggests that resistance in our isolate was the result of overexpression of the endogenous ERG11 and ABC transporter. PMID- 26162643 TI - Enzymatic Activity and Susceptibility to Antifungal Agents of Brazilian Environmental Isolates of Hortaea werneckii. AB - Four strains of Hortaea werneckii were isolated from different substrates in Brazil (a salt marsh macrophyte, a bromeliad and a marine zoanthid) and had their identification confirmed by sequencing of the 26S rDNA D1/D2 domain or ITS region. Most of the strains were able to express amylase, lipase, esterase, pectinase and/or cellulase, enzymes that recognize components of plant cells as substrates, but did not express albuminase, keratinase, phospholipase and DNAse, whose substrates are animal-related. Urease production was positive for all isolates, while caseinase, gelatinase and laccase production were variable among the strains. All the strains grew in media containing up to 30% NaCl. We propose that the primary substrate associated with H. werneckii is plant-related, in special in saline environments, where the fungus may live as a saprophyte and decomposer. Infection of animal-associated substrates would be secondary, with the fungus acting as an opportunistic animal pathogen. All strains were resistant to fluconazole and presented high MIC for amphotericin B, while they were susceptible to all the other antifungal agents tested. PMID- 26162644 TI - Effect of Trans, Trans-Farnesol on Pseudogymnoascus destructans and Several Closely Related Species. AB - Bat white-nose syndrome, caused by the psychrophilic fungus Pseudogymnoascus destructans, has dramatically reduced the populations of many hibernating North American bat species. The search for effective biological control agents targeting P. destructans is of great importance. We report that the sesquiterpene trans, trans-farnesol, which is also a Candida albicans quorum sensing compound, prevented in vitro conidial germination for at least 14 days and inhibited growth of preexisting hyphae of five P. destructans isolates in filtered potato dextrose broth at 10 degrees C. Depending on the inoculation concentrations, both spore and hyphal inhibition occurred upon exposure to concentrations as low as 15-20 uM trans, trans-farnesol. In contrast, most North American Pseudogymnoascus isolates were more tolerant to the exposure of trans, trans-farnesol. Our results suggest that some Candida isolates may have the potential to inhibit the growth of P. destructans and that the sesquiterpene trans, trans-farnesol has the potential to be utilized as a biological control agent. PMID- 26162645 TI - Sequence-Based Identification of a Zoophilic Strain of Trichophyton interdigitale in a Rare Case of Tinea Blepharo-Ciliaris Associated with Tinea Barbae. AB - Impaired hair at blepharo-ciliaris area by dermatophytes is a rare clinical entity. This infection is often misdiagnosed or underdiagnosed, being mistakenly referred to as an infection of bacterial origin. Herein, we present a rare case of tinea blepharo-ciliaris associated with tinea barbae in an adult male. Considering the two lesions of the patient, mycological examination was performed by phenotypic methods, including environmental electronic scanning microscopy. Trichophyton interdigitale zoophilic strain was identified as the etiological agent by direct examination of the hair, primary culture analysis of the developed colonies and PCR sequencing of the ITS1 region of the rDNA gene. Homology search showed 100% similarity with T. interdigitale (GenBank accession number: KC595993), Arthroderma vanbreuseghemii (GenBank accession number: JQ407190) and zoophilic strain of T. interdigitale (GenBank accession number: AY062119.1.). Four weeks of oral and local treatment with itraconazole (100 mg twice a day) and fluconazole 0.3% (eyedrops) induced complete remission. To our knowledge, this is the first report of tinea blepharo-ciliaris associated with tinea barbae in Romania. PMID- 26162646 TI - Clinical pharmacology of daikenchuto assessed by transit analysis using radiopaque markers in patients with colon cancer undergoing open surgery: a multicenter double-blind randomized placebo-controlled study (JFMC39-0902 additional study). AB - BACKGROUND: This exploratory trial was conducted to investigate whether daikenchuto accelerates the recovery of gastrointestinal function in patients undergoing open surgery for sigmoid or rectosigmoid cancer. METHODS: Eighty-eight patients who underwent colectomy at one of the 11 clinical trial sites in Japan from January 2009 to June 2011 were registered in the study. Patients received either placebo or daikenchuto (15.0 g/day, 5 g three times a day) from postoperative day 2 to postoperative day 8. The study end points included the gastrointestinal tract transit time evaluated with radiopaque markers and the time to first flatus. The safety profile of daikenchuto was also evaluated until postoperative day 8. RESULTS: Seventy-one patients (daikenchuto, n = 38; placebo, n = 33) were statistically analyzed. Although the number of radiopaque markers in the anal side of the small intestine at 6 h was significantly greater in the daikenchuto group than in the placebo group (15.19 vs 10.06, p = 0.008), the total transit analysis results and the mean time to first flatus did not differ significantly between the two groups. CONCLUSIONS: Daikenchuto has a positive effect on the resolution of delayed gastric emptying, but has a limited effect on the resolution of postoperative paralytic ileus after open surgery in patients with sigmoid or rectosigmoid cancer. Daikenchuto may contribute to early oral intake in the postoperative course. PMID- 26162648 TI - Impact of a brief intervention on self-regulation, self-efficacy and physical activity in older adults with type 2 diabetes. AB - Despite evidence of the benefits of physical activity, most individuals with type 2 diabetes do not meet physical activity recommendations. The purpose of this study was to test the efficacy of a brief intervention targeting self-efficacy and self-regulation to increase physical activity in older adults with type 2 diabetes. Older adults (Mage = 61.8 +/- 6.4) with type 2 diabetes or metabolic syndrome were randomized into a titrated physical activity intervention (n = 58) or an online health education course (n = 58). The intervention included walking exercise and theory-based group workshops. Self-efficacy, self-regulation and physical activity were assessed at baseline, post-intervention, and a follow-up. Results indicated a group by time effect for self-regulation [F(2,88) = 14.021, p < .001, eta (2) = .24] and self-efficacy [F(12,77) = 2.322, p < .05, eta (2) = .266] with increases in the intervention group. The intervention resulted in short-term increases in physical activity (d = .76, p < .01), which were partially maintained at the 6-month follow-up (d = .35, p < .01). The intervention increased short-term physical activity but was not successful at maintaining increases in physical activity. Similar intervention effects were observed in self-efficacy and self-regulation. Future research warrants adjusting intervention strategies to increase long-term change. PMID- 26162647 TI - First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis-results from a multicenter prospective randomized controlled trial and its post hoc analysis. AB - BACKGROUND: Infliximab (IFX) is one of the treatments of choice for corticosteroid-refractory and corticosteroid-dependent ulcerative colitis (UC). A high serum trough level of IFX (TL) is reported to be associated with sustained efficacy during maintenance treatment. As part of a phase 3 randomized controlled trial of IFX in UC, we assessed the predictive value of the first TL at week 2 for short- and long-term response. METHODS: Patients received intravenous IFX 5 mg/kg or placebo at weeks 0, 2, and 6. Patients with evidence of a response by week 8 continued treatment at weeks 14 and 22. TL was measured by enzyme-linked immunosorbent assay. Post hoc analysis was then performed for TL and clinical outcomes. RESULTS: Clinical response rate at week 8, the primary end point, was significantly higher in the IFX group than placebo (p = 0.005). The incidence of adverse events between groups was similar. Week 2 TL was significantly associated with a 14-week clinical activity index (CAI) remission. In multiple logistic regression analysis, the week 2 TL-to-CAI ratio (TL/CAI, odds ratio 8.07; 95% confidence interval 2.84-27.07, p < 0.001) was an independent factor correlating with 14-week CAI remission. The week 2 TL and TL/CAI were also significantly associated with 30-week mucosal healing. CONCLUSIONS: IFX was confirmed to be effective and safe in this population. Our results suggest that the first TL at week 2, in combination with clinical evaluation, is useful for predicting both short- and long-term outcomes, allowing an earlier decision between continuing IFX or switching to other options. PMID- 26162650 TI - HDX match software for the data analysis of top-down ECD-FTMS hydrogen/deuterium exchange experiments. AB - Hydrogen/deuterium exchange (HDX) combined with mass spectrometry is a powerful technique for studying protein structure. The recently developed top-down ECD FTMS HDX approach (Pan J. et al., JACS, 2008) allows determination of the hydrogen/deuterium exchange of a protein's amide bonds, down to the single residue resolution. One of the existing limitations of this technology has been the laborious manual analysis of the MS/MS spectra. Here we present a software program for processing the data from these experiments. This program assigns the c- and z-fragment ion series of the protein, and calculates the number of the exchanged amide protons for each fragment by fitting the theoretically predicted isotopic envelopes of the deuterated fragments to the experimental data. Graphical Abstract ?. PMID- 26162649 TI - Differentiation of Disaccharide Isomers by Temperature-Dependent In-Source Decay (TDISD) and DART-Q-TOF MS/MS. AB - Helium direct analysis in real time (He-DART) mass spectrometry (MS) of some compounds, polysaccharides, for example, usually tends to be challenging because of the occurrence of prominent in-source decay (ISD), which was considered as an undesired side reaction, as it complicated the resulting mass spectra. Our approach is to take advantage of an efficient and practical method termed the temperature-dependent ISD (TDISD) technique combined with fragmentation of the dehydrated dimers using DART Q-TOF tandem mass spectrometry for differentiation of disaccharide isomers. In this study, cross-ring cleavages and non-ovalent complexes were detected in the spectra of the saccharides. It was observed that the gas heater temperature had a significant effect on the absence or presence of signal in DART spectra. At high gas temperature, ions in high mass region began to appear. Based on the types of cross-ring cleavages and noncovalent complexes, disaccharide isomers with different linkage positions can be differentiated in both positive and negative ion modes at a lower DART gas temperature. Additionally, anomeric configurations were assigned on the basis of the relative abundance ratio of m/z 198:342 obtained by the comparison of the positive ion mode tandem mass spectrum of an alpha isomer dimer generated at higher DART gas temperature and that of the corresponding beta one. In general, this method is easy, fast, effective, and robust for identifying disaccharide isomers. PMID- 26162651 TI - The role of neighborhood in urban black adolescent marijuana use. AB - BACKGROUND: The present study examined the influence of neighborhood factors on transitions in marijuana involvement during adolescence in a sample of primarily low-income, urban Black youth. METHODS: 556 Black adolescents were interviewed annually beginning in first grade as part of a longitudinal study. Latent class analysis (LCA) was used to examine stages of marijuana involvement from 6th to 9th grades. The influence of neighborhood disorder, drug activity, violent crime, safety and disadvantage on transitions in marijuana involvement was tested using latent transition analysis (LTA). RESULTS: There was evidence for three stages of involvement: no involvement, offered, and use and problems. Involvement increased steadily during adolescence with a slightly greater risk to transition from offers to use between 6th and 7th grades. Neighborhood disorder (AOR=1.04, CI=1.00, 1.08), drug activity (AOR=1.12, CI=1.02, 1.22) and disadvantage (AOR=1.44, CI=1.10, 1.92) were associated with the transition from marijuana offers to use and problems. Neighborhood disorder (AOR=1.07, CI=1.02, 1.11), drug activity (AOR=1.19, CI=1.10, 1.29) and violent crime (AOR=1.17, CI=1.03, 1.32) were associated with transitioning rapidly from no involvement to use and problems. CONCLUSIONS: Understanding how neighborhoods could be organized and provided with supports to discourage marijuana use and promote non-drug using behaviors should be an important goal of any prevention program in low-income, urban Black neighborhoods. Enhancing citizen participation and mobilization to address the social processes of neighborhood disorder has the potential to reduce marijuana involvement in these neighborhoods. PMID- 26162652 TI - Functional status, time to transplantation, and survival benefit of kidney transplantation among wait-listed candidates. AB - BACKGROUND: In the context of an aging end-stage renal disease population with multiple comorbid conditions, transplantation professionals face challenges in evaluating the global health of patients awaiting kidney transplantation. Functional status might be useful for identifying which patients will derive a survival benefit from transplantation versus dialysis. STUDY DESIGN: Retrospective cohort study of wait-listed patients using data for functional status from a national dialysis provider linked to United Network for Organ Sharing registry data. SETTING & PARTICIPANTS: Adult kidney transplantation candidates added to the waiting list between 2000 and 2006. PREDICTOR: Physical Functioning scale of the Medical Outcomes Study 36-Item Short Form Health Survey, analyzed as a time-varying covariate. OUTCOMES: Kidney transplantation; survival benefit of transplantation versus remaining wait-listed. MEASUREMENTS: We used multivariable Cox regression to assess the association between physical function with study outcomes. In survival benefit analyses, transplantation status was modeled as a time-varying covariate. RESULTS: The cohort comprised 19,242 kidney transplantation candidates (median age, 51 years; 36% black race) receiving maintenance dialysis. Candidates in the lowest baseline Physical Functioning score quartile were more likely to be inactivated (adjusted HR vs highest quartile, 1.30; 95% CI, 1.21-1.39) and less likely to undergo transplantation (adjusted HR vs highest quartile, 0.64; 95% CI, 0.61-0.68). After transplantation, worse Physical Functioning score was associated with shorter 3 year survival (84% vs 92% for the lowest vs highest function quartiles). However, compared to dialysis, transplantation was associated with a statistically significant survival benefit by 9 months for patients in every function quartile. LIMITATIONS: Functional status is self-reported. CONCLUSIONS: Even patients with low function appear to live longer with kidney transplantation versus dialysis. For wait-listed patients, global health measures such as functional status may be more useful in counseling patients about the probability of transplantation than in identifying who will derive a survival benefit from it. PMID- 26162654 TI - Parental History of Cardiovascular Disease and Risk of ESRD in Women. PMID- 26162655 TI - Negative symptom domain prevalence across diagnostic boundaries: The relevance of diagnostic shifts. AB - Negative symptoms are included in diagnostic manuals as part of criteria for schizophrenia spectrum psychoses only, however some studies have found their presence in other diagnoses. This study sought to clarify negative symptom domain prevalence across diagnostic categories, while investigating whether negative symptoms predicted diagnostic shift over time. Scale for the Assessment of Negative Symptoms (SANS) data were collected at first presentation in 197 individuals presenting with first episode psychosis and again at one year follow up assessment. Negative symptoms were highest among individuals with schizophrenia and among those whose diagnosis shifted from non-schizophrenia spectrum at baseline to schizophrenia spectrum at follow-up. In a non schizophrenia spectrum group negative symptoms at baseline were not a significant predictor of diagnostic shift to schizophrenia spectrum diagnoses. The study suggests negative symptoms can present among individuals with non-schizophrenia spectrum diagnoses, although this is most relevant for individuals following diagnostic shift from non-schizophrenia spectrum to schizophrenia spectrum diagnoses. The findings support introduction of a negative symptom dimension when describing a range of psychotic illnesses, and indicate that further research investigating the evolution of negative symptoms in non-schizophrenia diagnoses is needed. PMID- 26162653 TI - Outcomes After Warfarin Initiation in a Cohort of Hemodialysis Patients With Newly Diagnosed Atrial Fibrillation. AB - BACKGROUND: Although warfarin is indicated to prevent ischemic strokes in most patients with atrial fibrillation (AF), evidence supporting its use in hemodialysis patients is limited. Our aim was to examine outcomes after warfarin therapy initiation, relative to no warfarin use, following incident AF in a large cohort of hemodialysis patients who had comprehensive prescription drug coverage through Medicare Part D. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients in the US Renal Data System undergoing maintenance hemodialysis who had AF newly diagnosed in 2007 to 2011, with Medicare Part D coverage, who had no recorded history of warfarin use. PREDICTOR: Warfarin therapy initiation, identified by a filled prescription within 30 days of the AF event. OUTCOMES: Death, ischemic stroke, hemorrhagic stroke, severe gastrointestinal bleeding, and composite outcomes. MEASUREMENTS: HRs estimated by applying Cox regression to an inverse probability of treatment and censoring weighted cohort. RESULTS: Of 12,284 patients with newly diagnosed AF, 1,838 (15%) initiated warfarin therapy within 30 days; however, ~70% discontinued its use within 1 year. In intention-to-treat analyses, warfarin use was marginally associated with a reduced risk of ischemic stroke (HR, 0.68; 95% CI, 0.47-0.99), but not with the other outcomes. In as-treated analyses, warfarin use was associated with reduced mortality (HR, 0.84; 95% CI, 0.73-0.97). LIMITATIONS: Short observation period, limited number of nonfatal events, limited generalizability of results to more affluent patients. CONCLUSIONS: In hemodialysis patients with incident AF, warfarin use was marginally associated with reduced risk of ischemic stroke, and there was a signal toward reduced mortality in as-treated analyses. These results support clinical equipoise regarding the use of warfarin in hemodialysis patients and underscore the need for randomized trials to fill this evidence gap. PMID- 26162656 TI - Lateralization for speech predicts therapeutic response to cognitive behavioral therapy for depression. AB - A prior study (Bruder, G.E., Stewart, J.W., Mercier, M.A., Agosti, V., Leite, P., Donovan, S., Quitkin, F.M., 1997. Outcome of cognitive-behavioral therapy for depression: relation of hemispheric dominance for verbal processing. Journal of Abnormal Psychology 106, 138-144.) found left hemisphere advantage for verbal dichotic listening was predictive of clinical response to cognitive behavioral therapy (CBT) for depression. This study aimed to confirm this finding and to examine the value of neuropsychological tests, which have shown promise for predicting antidepressant response. Twenty depressed patients who subsequently completed 14 weeks of CBT and 74 healthy adults were tested on a Dichotic Fused Words Test (DFWT). Patients were also tested on the National Adult Reading Test to estimate IQ, and word fluency, choice RT, and Stroop neuropsychological tests. Left hemisphere advantage on the DFWT was more than twice as large in CBT responders as in non-responders, and was associated with improvement in depression following treatment. There was no difference between responders and non-responders on neuropsychological tests. The results support the hypothesis that the ability of individuals with strong left hemisphere dominance to recruit frontal and temporal cortical regions involved in verbal dichotic listening predicts CBT response. The large effect size, sensitivity and specificity of DFWT predictions suggest the potential value of this brief and inexpensive test as an indicator of whether a patient will benefit from CBT for depression. PMID- 26162657 TI - Randomized trial on the effectiveness of long- and short-term psychotherapy on psychosocial functioning and quality of life during a 5-year follow-up. AB - Knowledge is incomplete on whether long-term psychotherapy is more effective than short-term therapy in treating mood and anxiety disorder, when measured by improvements in psychosocial functioning and life quality. In the Helsinki Psychotherapy Study, 326 outpatients with mood or anxiety disorder were randomized to solution-focused therapy (SFT), short-term psychodynamic psychotherapy (SPP), or long-term psychodynamic psychotherapy (LPP), and followed up for 5 years from the start of treatment. The outcome measures comprised 4 questionnaires on psychosocial functioning, assessing global social functioning (Social Adjustment Scale (SAS-SR), sense of coherence (Sense of Coherence Scale (SOC)), perceived competence (Self-Performance Survey), dispositional optimism (Life Orientation Test (LOT)), and 1 questionnaire assessing quality of life (Life Situation Survey (LSS)). Short-term therapies improved psychosocial functioning and quality of life more than LPP during the first year. The only exceptions were LOT and perceived competence, which did not differ between SPP and LPP. Later in the follow-up, SOC and perceived competence showed significantly more improvement in LPP than in the short-term therapy groups. No direct differences between SFT and SPP were noted. Short-term therapy has consistently more short-term effects on psychosocial functioning and quality of life than LPP, whereas LPP has some additional long-term benefits on psychosocial functioning. PMID- 26162658 TI - Post traumatic stress disorder and coping in a sample of adult survivors of the Italian earthquake. AB - The aim was to investigate the prevalence of post traumatic stress disorder (PTSD) in people who had left their damaged homes and were still living in temporary housing more than a year after the April 2009 L'Aquila (Italy) earthquake. In addition, we evaluated the differences in coping strategies implemented by persons who had and who did not have PTSD. A cross-sectional prevalence study was carried out on a sample of 281 people aged >18 years and living in temporary housing after the earthquake. The questionnaires used include the Davidson Trauma Scale and the Brief Cope. The prevalence of PTSD was 43%. Women and the non-employed were more vulnerable to PTSD, while, age and level of education were not associated with PTSD. Those with PTSD symptoms often employed maladaptive coping strategies for dealing with earthquake and had the highest scores in the domains of denial, venting, behavioral disengagement, self-blame. By contrast, those without PTSD generally had more adaptive coping mechanisms. Adults who were living in temporary housing after the earthquake experienced high rates of PTSD. The difference in coping mechanisms between those who have PTSD and those who do not also suggests that they influence the likeliness of developing PTSD. PMID- 26162659 TI - New findings support the association of DISC1 genetic variants with susceptibility to schizophrenia in the Han Chinese population. PMID- 26162660 TI - Internalized mental illness stigma and subjective well-being: The mediating role of psychological well-being. AB - This study examines the relationships between internalized stigma, psychological well-being, and subjective well-being in a sample of people with mental illness. We conducted a cross-sectional study with 213 outpatients from the Spanish public social care network. The results showed that (a) internalized stigma was significantly negatively correlated with psychological well-being and subjective well-being (affect balance and life satisfaction) (all correlations are significant with at least p<0.05; most with p<0.001), (b) the two types of well being were significantly positively correlated and regressions models were significant and (all correlations are at least p<0.01, and regression models are also significant), (c) the effect of internalized stigma on affect balance and life satisfaction was mediated by psychological well-being. The component of internalized stigma most consistently associated with both types of well-being was alienation (life satisfaction: B=-0.35, p=0.001; affect balance: B=-0.38, p=0.001). These findings should be confirmed in future longitudinal or experimental research. On the basis of these results we recommend that interventions to combat self-stigma aim to reduce feelings of alienation and improve self-acceptance and other aspects of positive psychological functioning. PMID- 26162661 TI - Obsessive-compulsive symptom dimensions and insomnia: The mediating role of anxiety sensitivity cognitive concerns. AB - Existing research on the relationship between obsessive-compulsive disorder (OCD) and insomnia is scarce. Moreover, no research has examined potential mechanisms that may account for the observed relations among OCD and sleep difficulties. The cognitive concerns subscale of anxiety sensitivity (AS), which reflects fears of mental incapacitation, has been linked to both symptoms of OCD and insomnia and may serve as a mechanism for increasing sleep disturbance among patients with OCD. The current study examined the relationship between OCD symptoms and insomnia and the potential mediating role of AS cognitive concerns. The sample consisted of 526 individuals recruited through Amazon's Mechanical Turk (Mturk), an online crowdsourcing marketplace. Results revealed distinct associations between the unacceptable thoughts domain of OCD and symptoms of insomnia. Additionally, AS cognitive concerns mediated the relationship between these constructs. Future research should seek to replicate these findings using clinical samples and prospective designs. PMID- 26162662 TI - Expectancies of success as a predictor of negative symptoms reduction over 18 months in individuals with schizophrenia. AB - Negative symptoms are often enduring and lead to poor functional outcomes in individuals with schizophrenia. The cognitive model of negative symptoms proposes that low expectancies of success contribute to the development and maintenance of negative symptoms; however, longitudinal investigations assessing these beliefs and negative symptoms are needed. The current study examined whether an individual's baseline expectancies of success - one's beliefs about future success and goal attainment - predicted negative symptoms reduction over 18 months in individuals with schizophrenia-spectrum disorders (n=118). Data were collected at baseline, 9 months, and 18 months as part of a randomized controlled trial of Illness Management and Recovery. A mixed effects regression analysis revealed a significant reduction in negative symptoms over time, with a significant interaction effect between time and baseline expectancies of success. After controlling for baseline negative symptoms, demographic variables, and treatment conditions, those with high and moderate baseline expectancies of success evidenced a significant reduction in negative symptoms at 18 months, while those with low baseline expectancies of success did not evidence reduced negative symptoms. Findings support the cognitive model of negative symptoms and suggest that expectancies of success may be a useful treatment target for interventions aimed at reducing negative symptoms. PMID- 26162663 TI - Does aging affect source monitoring and cognitive confidence in schizophrenia? Preliminary results. AB - This study tested the influence of aging on source-monitoring and cognitive confidence deficits in schizophrenia. Younger (n=13) and older (n=10) schizophrenia patients were compared with younger (n=17) and older (n=10) healthy controls in the source-monitoring task. These preliminary results suggest that age negatively influences old/new item recognition, but not source monitoring, in both groups. Age has a negative impact on subjective confidence, but no interaction between group and age was found. PMID- 26162664 TI - Cognitive mapping deficits in schizophrenia: Evidence from clinical correlates of visuospatial transformations. AB - The 'cognitive mapping' component of spatial cognition, namely - the allocentric/egocentric function and its relation to symptoms in schizophrenia is relatively unexplored. In this study, we compared schizophrenia patients (N=44) to demographically-matched healthy controls (N=43) using computer-administered visuospatial transformation tasks with egocentric and allocentric components and analyzed their correlation with symptoms. Significant diagnosis X task-type interaction effect was seen on task accuracy. Patients performed significantly worse than controls in the allocentric letter rotation task (LRT) but not in the egocentric people rotation task (PRT). Accuracy in the LRT was significantly lesser than in PRT among patients but not among controls. Patients were significantly slower as compared to controls in both tasks. Both groups took longer to perform PRT as compared to LRT. LRT accuracy showed significant negative correlation with total positive symptoms as well as negative symptoms scores. Angle of rotation, perspective (front-facing/back-facing), orientation (mirrored/normal), and stimulus type (letter/number) were found to significantly influence performance in both groups of subjects. The present data support the finding that there is a differential impairment of allocentric abilities in schizophrenia patients. Further systematic research in this area may facilitate better understanding of schizophrenia pathogenesis. PMID- 26162665 TI - Cooperativity between various types of polar solute-solvent interactions in aqueous media. AB - Partition coefficients of seven low molecular weight compounds were measured in multiple aqueous two-phase systems (ATPSs) formed by pairs of different polymers. The ionic composition of each ATPS was varied to include 0.01M sodium phosphate buffer (NaPB), pH 7.4 and 0.1M Na2SO4, 0.15M NaCl, and 0.15M NaClO4 all in 0.01M NaPB, pH 7.4. The differences between the solvent features of the coexisting phases in all the ATPSs were estimated from partitioning of a homologous series of dinitrophenylated-amino acids and by the solvatochromic method. The solute specific coefficients for the compounds examined were determined by the multiple linear regression analysis using the modified linear solvation energy relationship equation. It is established that the solute specific coefficients characterizing different types of the solute-water interactions (dipole-dipole, dipole-ion, and H-bonding) for a given solute change in the presence of different salt additives in the solute specific manner. It is also found that these characteristics are linearly interrelated. It is suggested that there is a cooperativity between various types of solute-water interactions governed by the solute structure. PMID- 26162666 TI - Influence of particle size and shell thickness of core-shell packing materials on optimum experimental conditions in preparative chromatography. AB - The applicability of core-shell phases in preparative separations was studied by a modeling approach. The preparative separations were optimized for two compounds having bi-Langmuir isotherms. The differential mass balance equation of chromatography was solved by the Rouchon algorithm. The results show that as the size of the core increases, larger particles can be used in separations, resulting in higher applicable flow rates, shorter cycle times. Due to the decreasing volume of porous layer, the loadability of the column dropped significantly. As a result, the productivity and economy of the separation decreases. It is shown that if it is possible to optimize the size of stationary phase particles for the given separation task, the use of core-shell phases are not beneficial. The use of core-shell phases proved to be advantageous when the goal is to build preparative column for general purposes (e.g. for purification of different products) in small scale separations. PMID- 26162667 TI - Computational investigation of longitudinal diffusion, eddy dispersion, and trans particle mass transfer in bulk, random packings of core-shell particles with varied shell thickness and shell diffusion coefficient. AB - In recent years, chromatographic columns packed with core-shell particles have been widely used for efficient and fast separations at comparatively low operating pressure. However, the influence of the porous shell properties on the mass transfer kinetics in core-shell packings is still not fully understood. We report on results obtained with a modeling approach to simulate three-dimensional advective-diffusive transport in bulk random packings of monosized core-shell particles, covering a range of reduced mobile phase flow velocities from 0.5 up to 1000. The impact of the effective diffusivity of analyte molecules in the porous shell and the shell thickness on the resulting plate height was investigated. An extension of Giddings' theory of coupled eddy dispersion to account for retention of analyte molecules due to stagnant regions in porous shells with zero mobile phase flow velocity is presented. The plate height equation involving a modified eddy dispersion term excellently describes simulated data obtained for particle-packings with varied shell thickness and shell diffusion coefficient. It is confirmed that the model of trans-particle mass transfer resistance of core-shell particles by Kaczmarski and Guiochon [42] is applicable up to a constant factor. We analyze individual contributions to the plate height from different mass transfer mechanisms in dependence of the shell parameters. The simulations demonstrate that a reduction of plate height in packings of core-shell relative to fully porous particles arises mainly due to reduced trans-particle mass transfer resistance and transchannel eddy dispersion. PMID- 26162668 TI - Defining the property space for chromatographic ligands from a homologous series of mixed-mode ligands. AB - A homologous ligand library based on the commercially-available Nuvia cPrime ligand was generated to systematically explore various features of a multimodal cation-exchange ligand and to identify structural variants that had significantly altered chromatographic selectivity. Substitution of the polar amide bond with more hydrophobic chemistries was found to enhance retention while remaining hydrophobically-selective for aromatic residues. In contrast, increasing the solvent exposure of the aromatic ring was observed to strengthen the ligand affinity for both types of hydrophobic residues. An optimal linker length between the charged and hydrophobic moieties was also observed to enhance retention, balancing the steric accessibility of the hydrophobic moiety with its ability to interact independently of the charged group. The weak pKa of the carboxylate charge group was found to have a notable impact on protein retention on Nuvia cPrime at lower pH, increasing hydrophobic interactions with the protein. Substituting the charged group with a sulfonic acid allowed this strong MM ligand to retain its electrostatic-dominant character in this lower pH range. pH gradient experiments were also carried out to further elucidate this pH dependent behavior. A single QSAR model was generated using this accumulated experimental data to predict protein retention across a range of multimodal and ion exchange systems. This model could correctly predict the retention of proteins on resins that were not included in the original model and could prove quite powerful as an in silico approach toward designing more effective and differentiated multimodal ligands. PMID- 26162669 TI - Simple determination of fluoride in biological samples by headspace solid-phase microextraction and gas chromatography-tandem mass spectrometry. AB - A simple and convenient method to detect fluoride in biological samples was developed. This method was based on derivatization with 2 (bromomethyl)naphthalene, headspace solid phase microextraction (HS-SPME) in a vial, and gas chromatography-tandem mass spectrometric detection. The HS-SPME parameters were optimized as follows: selection of CAR/PDMS fiber, 0.5% 2 (bromomethyl)naphthalene, 250 mg/L 15-crown-5-ether as a phase transfer catalyst, extraction and derivatization temperature of 95 degrees C, heating time of 20 min and pH of 7.0. Under the established conditions, the lowest limits of detection were 9 and 11 MUg/L in 1.0 ml of plasma and urine, respectively, and the intra- and inter-day relative standard deviation was less than 7.7% at concentrations of 0.1 and 1.0 mg/L. The calibration curve showed good linearity of plasma and urine with r=0.9990 and r=0.9992, respectively. This method is simple, amenable to automation and environmentally friendly. PMID- 26162670 TI - Biotransformations of organic compounds mediated by cultures of Aspergillus niger. AB - Many different organic compounds may be converted by microbial biotransformation to high-value products for the chemical and pharmaceutical industries. This review summarizes the use of strains of Aspergillus niger, a well-known filamentous fungus used in numerous biotechnological processes, for biochemical transformations of organic compounds. The substrates transformed include monocyclic, bicyclic, and polycyclic aromatic hydrocarbons; azaarenes, epoxides, chlorinated hydrocarbons, and other aliphatic and aromatic compounds. The types of reactions performed by A. niger, although not unique to this species, are extremely diverse. They include hydroxylation, oxidation of various functional groups, reduction of double bonds, demethylation, sulfation, epoxide hydrolysis, dechlorination, ring cleavage, and conjugation. Some of the products may be useful as new investigational drugs or chemical intermediates. PMID- 26162671 TI - Understanding the intracellular effects of yeast extract on the enhancement of Fc fusion protein production in Chinese hamster ovary cell culture. AB - Yeast extract (YE), as a non-animal source additive for mammalian cell culture medium, has been widely used for manufacturing of therapeutic proteins. In the present study, one particular YE was found to have significantly improved the specific productivity (q p) of Fc-fusion protein in recombinant Chinese hamster ovary (rCHO) cell culture. In order to elucidate the intracellular effects of YE on protein productivity, steps of the target protein synthesis process were investigated to unveil their variations caused by YE addition. Stepwise analysis on Fc-fusion protein synthesis process showed that YE enhanced Fc-fusion protein gene transcription with cell cycle arrest at G1 phase; mammalian target of rapamycin (mTOR) signaling pathway was activated to enhance the translation of Fc fusion protein, and the block in post-translational steps of Fc-fusion protein was alleviated by YE addition as well. Our results revealed the responses of multiple protein production steps to the addition of YE and provided a practical guidance for the separation and application of active compounds from hydrolysates. PMID- 26162672 TI - Convergence of multiple markers and analysis methods defines the genetic distinctiveness of cryptic pitvipers. AB - Using multiple markers and multiple analytical approaches is critical for establishing species boundaries reliably, especially so in the case of cryptic species. Despite development of new and powerful analytical methods, most studies continue to adopt a few, with the choice often being subjective. One such example is routine analysis of Amplified Fragment Length Polymorphism (AFLP) data using population genetic models despite disparity between method assumptions and data properties. The application of newly developed methods for analyzing this dominant marker may not be entirely clear in the context of species delimitation. In this study, we use AFLPs and mtDNA to investigate cryptic speciation in the Trimeresurus macrops complex that belongs to a taxonomically difficult lineage of Asian pitvipers. We analyze AFLPs using population genetic, phylogenetic, multivariate statistical, and Bayes Factor Delimitation methods. A gene tree from three mtDNA markers provided additional evidence. Our results show that the inferences about species boundaries that can be derived from population genetic analysis of AFLPs have certain limitations. In contrast, four multivariate statistical analyses produced clear clusters that are consistent with each other, as well as with Bayes Factor Delimitation results, and with mtDNA and total evidence phylogenies. Furthermore, our results concur with allopatric distributions and patterns of variation in individual morphological characters previously identified in the three proposed species: T. macrops sensu stricto, T. cardamomensis, and T. rubeus. Our study provides evidence for reproductive isolation and genetic distinctiveness that define these taxa as full species. In addition, we re-emphasize the importance of examining congruence of results from multiple methods of AFLP analysis for inferring species diversity. PMID- 26162673 TI - Comments on the Long-term Prognosis of Patients With Non-ST-segment Elevation Acute Myocardial Infarction and Coronary Arteries Without Significant Stenosis. Response. PMID- 26162674 TI - A compound heterozygous mutation of ABCC8 gene causing a diazoxide-unresponsive congenital hyperinsulinism with an atypical form: Not a focal lesion in the pancreas reported by 18F-DOPA-PET/CT scan. AB - Congenital hyperinsulinism (CHI) is a severe heterogeneous disorder due to dysregulation of insulin secretion from the pancreatic beta-cells leading to severe hypoglycemia in infancy. 18-fluoro-l-3,4-dihydroxyphenylalanine positron emission tomography ((18)F-DOPA-PET)/CT is a useful tool in distinguishing between focal and diffuse disease preoperatively. But recent studies have suggested that the scanning may not be accurate as initially estimated. In this study we characterize a case of CHI with a compound heterozygous mutation of ABCC8 gene. The results of clinical investigation, gene mutation analysis, (18)F DOPA-PET/CT scan, and pathological examination showed some new characteristics that have never been reported. The patient was unresponsive to medical therapy with diazoxide and received pancreatectomy twice. Genetic analysis identified a compound heterozygous mutation in ABCC8 genes. Imaging with (18)F-DOPA-PET/CT indicated a focal lesion in the head of the pancreas. The pathological diagnosis was an atypical form of CHI. The patient presented with a phenotype of atypical CHI unresponsive to diazoxide. It is considered that a relationship existed between the compound heterozygous mutation and the atypical form. (18)F-DOPA PET/CT is a useful tool in distinguishing between focal and diffuse forms preoperatively but the accuracy is not 100%. The scan result is best combined with genetic analysis and intra-operative biopsy to confirm the histological subtypes. The combination will provide the optimal strategy for the surgical treatment of patients with CHI. PMID- 26162675 TI - Phenotypic screen for RNAi effects in the codling moth Cydia pomonella. AB - RNAi-based technologies have the potential to augment, or replace existing pest management strategies. However, some insect taxa are less susceptible to the induction of the post-transcriptional gene silencing effect than others, such as the Lepidoptera. Here we describe experiments to investigate the induction of RNAi in the codling moth, Cydia pomonella, a major lepidopteran pest of apple, pear, and walnut. Prior to a knockdown screen, fluorescently labeled small interfering RNA (siRNA) and double-stranded RNA (dsRNA) derived from green fluorescent protein (GFP) coding sequence were delivered to the surface of artificial diet to which neonate larvae were introduced and subsequently examined for the distribution of fluorescence in their tissues. Fluorescence was highly concentrated in the midgut but its presence in other tissues was equivocal. Next, dsRNAs were made for C. pomonella genes orthologous to those that have well defined deleterious phenotypes in Drosophila melanogaster. A screen was conducted using dsRNAs encoding cullin-1 (Cpcul1), maleless (Cpmle), musashi (Cpmsi), a homeobox gene (CpHbx), and pumilio (Cppum). The dsRNAs designed from these target genes were administered to neonate larvae by delivery to the surface of the growth medium. None of the dsRNA treatments affected larval viability, however Cpcul1-dsRNA had a significant effect on larval growth, with the average length of larvae about 3mm, compared to about 4mm in the control groups. Measurement of Cpcul1 transcript levels by quantitative real-time PCR (qRT-PCR) revealed a dose dependent RNAi effect in response to increasing amount of Cpcul1-dsRNA. Despite their reduced size, Cpcul1-dsRNA-treated larvae molted normally and matured to adulthood in a manner similar to controls. In an additional experiment, Cpcul1 siRNA was found to induce similar stunting effect as that induced by Cpcul1 dsRNA. PMID- 26162677 TI - Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. AB - PURPOSE: Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients. METHODS: The Acute Kidney Injury-Epidemiologic Prospective Investigation (AKI-EPI) study was an international cross-sectional study performed in 97 centers on patients during the first week of ICU admission. We measured AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and outcomes at hospital discharge. RESULTS: A total of 1032 ICU patients out of 1802 [57.3%; 95% confidence interval (CI) 55.0-59.6] had AKI. Increasing AKI severity was associated with hospital mortality when adjusted for other variables; odds ratio of stage 1 = 1.679 (95% CI 0.890-3.169; p = 0.109), stage 2 = 2.945 (95% CI 1.382-6.276; p = 0.005), and stage 3 = 6.884 (95% CI 3.876-12.228; p < 0.001). Risk-adjusted rates of AKI and mortality were similar across the world. Patients developing AKI had worse kidney function at hospital discharge with estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) in 47.7% (95% CI 43.6 51.7) versus 14.8% (95% CI 11.9-18.2) in those without AKI, p < 0.001. CONCLUSIONS: This is the first multinational cross-sectional study on the epidemiology of AKI in ICU patients using the complete KDIGO criteria. We found that AKI occurred in more than half of ICU patients. Increasing AKI severity was associated with increased mortality, and AKI patients had worse renal function at the time of hospital discharge. Adjusted risks for AKI and mortality were similar across different continents and regions. PMID- 26162678 TI - The consistent inconsistency of fluid challenges in the ICU: We should reflect on extreme variation in our practice. PMID- 26162679 TI - Correction for Slik et al., An estimate of the number of tropical tree species. PMID- 26162681 TI - Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells. AB - The organometallic "half-sandwich" compound [Os(eta(6)-p-cymene)(4-(2-pyridylazo) N,N-dimethylaniline)I]PF6 is 49* more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH dehydrogenase) in the electron transport chain. ND5 is a proton pump, helping to maintain the coupling gradient in mitochondria. The identified mutations correspond to known protein variants (p.I257V, p.N447S, and p.L517P), not reported previously in epithelial ovarian cancer. Time-series RNA sequencing suggested that osmium-exposed A2780 cells undergo a metabolic shunt from glycolysis to oxidative phosphorylation, where defective machinery, associated with mutations in complex I, could enhance activity. Downstream events, measured by time-series reverse-phase protein microarrays, high-content imaging, and flow cytometry, showed a dramatic increase in mitochondrially produced reactive oxygen species (ROS) and subsequent DNA damage with up regulation of ATM, p53, and p21 proteins. In contrast to platinum drugs, exposure to this organo-osmium compound does not cause significant apoptosis within a 72-h period, highlighting a different mechanism of action. Superoxide production in ovarian, lung, colon, breast, and prostate cancer cells exposed to three other structurally related organo-Os(II) compounds correlated with their antiproliferative activity. DNA damage caused indirectly, through selective ROS generation, may provide a more targeted approach to cancer therapy and a concept for next-generation metal-based anticancer drugs that combat platinum resistance. PMID- 26162680 TI - Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication. AB - Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L. Primer retention does not lead immediately to depletion, as the persistent RNA is fully incorporated in mitochondrial DNA. However, the retained primers present an obstacle to the mitochondrial DNA polymerase gamma in subsequent rounds of replication and lead to the catastrophic generation of a double-strand break at the origin when the resulting gapped molecules are copied. Hence, the essential role of RNase H1 in mitochondrial DNA replication is the removal of primers at the origin of replication. PMID- 26162682 TI - Conformational kinetics reveals affinities of protein conformational states. AB - Most biological reactions rely on interplay between binding and changes in both macromolecular structure and dynamics. Practical understanding of this interplay requires detection of critical intermediates and determination of their binding and conformational characteristics. However, many of these species are only transiently present and they have often been overlooked in mechanistic studies of reactions that couple binding to conformational change. We monitored the kinetics of ligand-induced conformational changes in a small protein using six different ligands. We analyzed the kinetic data to simultaneously determine both binding affinities for the conformational states and the rate constants of conformational change. The approach we used is sufficiently robust to determine the affinities of three conformational states and detect even modest differences in the protein's affinities for relatively similar ligands. Ligand binding favors higher affinity conformational states by increasing forward conformational rate constants and/or decreasing reverse conformational rate constants. The amounts by which forward rate constants increase and reverse rate constants decrease are proportional to the ratio of affinities of the conformational states. We also show that both the affinity ratio and another parameter, which quantifies the changes in conformational rate constants upon ligand binding, are strong determinants of the mechanism (conformational selection and/or induced fit) of molecular recognition. Our results highlight the utility of analyzing the kinetics of conformational changes to determine affinities that cannot be determined from equilibrium experiments. Most importantly, they demonstrate an inextricable link between conformational dynamics and the binding affinities of conformational states. PMID- 26162683 TI - Determination of clinically significant tests for antiphospholipid antibodies and cutoff levels for obstetric antiphospholipid syndrome. AB - OBJECTIVE: The objective of this paper is to determine which kinds of assays for antiphospholipid antibodies (aPL) should be tested for clinical practice for patients with recurrent pregnancy loss (RPL). MATERIALS AND METHODS: We studied 560 patients with a history of RPL prospectively. We determined the obstetric significance of 11 commercially available tested assays for lupus anticoagulant (LA)-aPTT StaClot, phosphatidylserine-dependent antiprothrombin (aPS/PT) IgG, IgM, classical cardiolipin (CL) IgG, IgM, CL IgG, IgM, IgA, and beta2glycoprotein I (beta2GPI) IgG, IgM, IgA Phadia. Obstetric significance was defined as the potential for anticoagulant therapy to improve the subsequent live birth rate, or a difference in the live birth rate between positive and negative untreated cases. RESULTS: The LA-aPTT StaClot assay and aPS/PT IgG assay, but not CL IgG, were found to have obstetric significance. Our conventional tests covered positive cases with the aPS/PT IgM and classical CL IgG assays. The results of the LA-aPTT StaClot, LA-aPTT and LA-RVVT assays showed different distributions, although strong or moderate correlation was observed. CONCLUSION: LA-aPTT StaClot and aPS/PT IgG might be suitable for use in routine practice for patients with RPL. Each test for aPL should be ascertained for obstetric significance, because similar assays may have different outcomes. PMID- 26162684 TI - Relative efficacy and safety of tacrolimus, mycophenolate mofetil, and cyclophosphamide as induction therapy for lupus nephritis: a Bayesian network meta-analysis of randomized controlled trials. AB - AIMS: This study aimed to assess the relative efficacy and safety of tacrolimus, mycophenolate mofetil (MMF) and cyclophosphamide (CYC) as induction therapy for lupus nephritis. METHODS: Randomized controlled trials (RCTs) examining the efficacy and safety of tacrolimus, MMF and CYC for induction therapy in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs. RESULTS: Nine RCTs including 972 patients met the inclusion criteria and pair wise comparisons were performed, including 11 direct comparisons. Tacrolimus showed a significantly higher overall response rate (complete remission plus partial remission) than CYC (OR 2.35, 95% confidence interval (CI) 1.03-5.45), and was more efficacious than MMF (OR 1.60, 95% CI 0.70-3.57). MMF was superior to CYC in terms of overall response (OR 1.45, 95% CI 0.96-2.42). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tacrolimus had the highest probability of being the best treatment for achieving the overall response (SUCRA = 0.9321), followed by MMF (SUCRA = 0.5385) and CYC (SUCRA = 0.0294). In terms of safety, tacrolimus showed the highest probability of decreasing the risk of serious infections (SUCRA = 0.9253), followed by MMF (SUCRA = 0.4027) and CYC (SUCRA = 0.1720). CONCLUSIONS: Tacrolimus was the most efficacious induction treatment for patients with lupus nephritis, and had the highest probability of decreasing the risk of serious infections. Higher remission rates combined with a more favorable safety profile suggest that MMF is superior to CYC as induction treatment in these patients. PMID- 26162676 TI - Fluid challenges in intensive care: the FENICE study: A global inception cohort study. AB - BACKGROUND: Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC. METHODS: This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC. RESULTS: 2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59%, CI 57-61%). In 43% (CI 41 45%) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36%, CI 34-37%). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22%, CI 20-24%). No safety variable for the FC was used in 72% (CI 70-74%) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response. CONCLUSIONS: The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account. PMID- 26162686 TI - Lupus Impact Tracker is responsive to physician and patient assessed changes in systemic lupus erythematosus. AB - OBJECTIVE: To evaluate the responsiveness of Lupus Impact Tracker (LIT) to changes in physician and patient disease activity assessments over time. METHODS: Available longitudinal data from routine patient care visits on LIT, physician assessed disease activity (physician global assessment (PGA), SELENA-SLEDAI score, SELENA Flare Index (SFI)), and patient-reported changes in systemic lupus erythematosus (SLE) health status were analyzed. Significant, clinically important change (worsening or improvement) in physician disease activity assessment or patient-reported SLE health status were judged using the following criteria: change of 0.3 on PGA, 4 on SELENA-SLEDAI, change in SFI status over time, and change of 2 in either direction in patient-reported SLE health status. Mixed model regression analysis was used to compare changes in LIT using the above criteria. RESULTS: There were 1184 observations with significant changes in physician disease activity or patient-reported measure for 182 patients' data across 1364 visits. Patients' mean (SD) age and SELENA-SLEDAI were 43.5 (13.2) years and 6.4 (7.3) respectively. LIT mean scores decreased by more than 3 with improvement in PGA (standardized response mean -0.26, p < 0.05), while it increased by more than 5 with worsening in SELENA-SLEDAI (standardized response mean 0.42, p = 0.01). Mean change in LIT of greater than +/-3 was noted with change in SFI status (p < 0.05). Mean LIT score decreased by greater than 4 and increased by greater than 2 with patient-reported improvement and worsening in SLE health status respectively (p < 0.05). CONCLUSIONS: LIT is responsive to physician-assessed and patient-assessed changes in disease status. A mean LIT change of 2-4 may represent a significant clinical change in LIT. It is an effective tool that may be used by patients and physicians in tracking disease impact in SLE patients. PMID- 26162685 TI - Antiphospholipid syndrome, antiphospholipid antibodies and solid organ transplantation. AB - Antiphospholipid syndrome is considered a high risk factor for any kind of surgery. Considering that all solid organ transplants are critically dependent on the patency of vascular anastomosis, there is much concern about the consequences this pro-thrombotic condition may have on transplantation. Relatively little information is available in the literature assessing the real risk that antiphospholipid syndrome or the presence of antiphospholipid antibodies represent in solid organ transplantation. The aim of this article is to review the literature related to transplantation of solid organs in patients diagnosed with antiphospholipid syndrome or patients with positive antiphospholipid antibodies. PMID- 26162687 TI - Small Molecule Inhibition of MDM2-p53 Interaction Augments Radiation Response in Human Tumors. AB - MDM2-p53 interaction and downstream signaling affect cellular response to DNA damage. AMG 232 is a potent small molecule inhibitor that blocks the interaction of MDM2 and p53. We examined the capacity of AMG 232 to augment radiation response across a spectrum of human tumor cell lines and xenografts. AMG 232 effectively inhibited proliferation and enhanced radiosensitivity via inhibition of damage repair signaling. Combined AMG 232 and radiation treatment resulted in the accumulation of gammaH2AX-related DNA damage and induction of senescence with promotion of apoptotic and/or autophagic cell death. Several molecules involved in senescence, autophagy, and apoptosis were specifically modulated following the combined AMG 232/radiation treatment, including FoxM1, ULK-1, DRAM, and BAX. In vivo xenograft studies confirmed more potent antitumor and antiangiogenesis efficacy with combined AMG 232/radiation treatment than treatment with drug or radiation alone. Taken together, these data identify the capacity of AMG 232 to augment radiation response across a variety of tumor types harboring functional p53. PMID- 26162688 TI - Histone Deacetylase Inhibitors Inhibit Rhabdomyosarcoma by Reactive Oxygen Species-Dependent Targeting of Specificity Protein Transcription Factors. AB - The two major types of rhabdomyosarcoma (RMS) are predominantly diagnosed in children, namely embryonal (ERMS) and alveolar (ARMS) RMS, and patients are treated with cytotoxic drugs, which results in multiple toxic side effects later in life. Therefore, development of innovative chemotherapeutic strategies is imperative, and a recent genomic analysis suggested the potential efficacy of reactive oxygen species (ROS)-inducing agents. Here, we demonstrate the efficacy of the potent histone deacetylase (HDAC) inhibitors, panobinostat and vorinostat, as agents that inhibit RMS tumor growth in vivo, induce apoptosis, and inhibit invasion of RD and Rh30 RMS cell lines. These effects are due to epigenetic repression of cMyc, which leads to decreased expression of cMyc-regulated miRs 17, -20a, and -27a; upregulation of ZBTB4, ZBTB10, and ZBTB34; and subsequent downregulation of Sp transcription factors. We also show that inhibition of RMS cell growth, survival and invasion, and repression of Sp transcription factors by the HDAC inhibitors are independent of histone acetylation but reversible after cotreatment with the antioxidant glutathione. These results show a novel ROS dependent mechanism of antineoplastic activity for panobinostat and vorinostat that lies outside of their canonical HDAC-inhibitory activity and demonstrates the potential clinical utility for treating RMS patients with ROS-inducing agents. PMID- 26162690 TI - Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302). AB - Given the bulky nature of nanotherapeutics relative to small molecules, it is hypothesized that effective tumor delivery and penetration are critical barriers to their clinical activity. HER2-targeted PEGylated liposomal doxorubicin (MM 302, HER2-tPLD) is an antibody-liposomal drug conjugate designed to deliver doxorubicin to HER2-overexpressing cancer cells while limiting uptake into nontarget cells. In this work, we demonstrate that the administration and appropriate dose sequencing of cyclophosphamide can improve subsequent MM-302 delivery and enhance antitumor activity in preclinical models without negatively affecting nontarget tissues, such as the heart and skin. We demonstrate that this effect is critically dependent on the timing of cyclophosphamide administration. Furthermore, the effect was found to be unique to cyclophosphamide and related analogues, and not shared by other agents, such as taxanes or eribulin, under the conditions examined. Analysis of the cyclophosphamide-treated tumors suggests that the mechanism for improved MM-302 delivery involves the induction of tumor cell apoptosis, reduction of overall tumor cell density, substantial lowering of interstitial fluid pressure, and increasing vascular perfusion. The novel dosing strategy for cyclophosphamide described herein is readily translatable to standard clinical regimens, represents a potentially significant advance in addressing the drug delivery challenge, and may have broad applicability for nanomedicines. This work formed the basis for clinical evaluation of cyclophosphamide for improving liposome deposition as part of an ongoing phase I clinical trial of MM-302 in HER2-positive metastatic breast cancer. PMID- 26162689 TI - Small Molecule Inhibition of MERTK Is Efficacious in Non-Small Cell Lung Cancer Models Independent of Driver Oncogene Status. AB - Treatment of non-small cell lung cancer (NSCLC) has been transformed by targeted therapies directed against molecular aberrations specifically activated within an individual patient's tumor. However, such therapies are currently only available against a small number of such aberrations, and new targets and therapeutics are needed. Our laboratory has previously identified the MERTK receptor tyrosine kinase (RTK) as a potential drug target in multiple cancer types, including NSCLC. We have recently developed UNC2025--the first-in-class small molecule inhibitor targeting MERTK with pharmacokinetic properties sufficient for clinical translation. Here, we utilize this compound to further validate the important emerging biologic functions of MERTK in lung cancer pathogenesis, to establish that MERTK can be effectively targeted by a clinically translatable agent, and to demonstrate that inhibition of MERTK is a valid treatment strategy in a wide variety of NSCLC lines independent of their driver oncogene status, including in lines with an EGFR mutation, a KRAS/NRAS mutation, an RTK fusion, or another or unknown driver oncogene. Biochemically, we report the selectivity of UNC2025 for MERTK, and its inhibition of oncogenic downstream signaling. Functionally, we demonstrate that UNC2025 induces apoptosis of MERTK-dependent NSCLC cell lines, while decreasing colony formation in vitro and tumor xenograft growth in vivo in murine models. These findings provide further evidence for the importance of MERTK in NSCLC, and demonstrate that MERTK inhibition by UNC2025 is a feasible, clinically relevant treatment strategy in a wide variety of NSCLC subtypes, which warrants further investigation in clinical trials. PMID- 26162691 TI - Pathophysiology of mitochondrial disease causing epilepsy and status epilepticus. AB - Epilepsy is part of the clinical phenotype in nearly 40% of children with mitochondrial disease, yet the underlying molecular mechanisms remain poorly understood. Energy depletion has been postulated as the cause of mitochondrial epilepsy, but if this were the case, then 100% of patients with mitochondrial disease would be expected to present with seizures. This review explores other potential disease mechanisms underlying mitochondrial epilepsy, including oxidative stress, impaired calcium homeostasis, immune dysfunction, and deficiency of vitamins, cofactors, reducing equivalents, and other metabolites. Different mechanisms are likely to predominate in different mitochondrial disorders, since mitochondrial function varies between neurons and astrocytes, between different types of neurons, and in different brain regions. Systematic studies in cell and animal models of mitochondrial disease are needed in order to develop effective therapies for mitochondrial epilepsy. This article is part of a Special Issue entitled "Status Epilepticus". PMID- 26162693 TI - Multivariate Curve Resolution Applied to Hyperspectral Imaging Analysis of Chocolate Samples. AB - This paper shows the application of Raman and infrared hyperspectral imaging combined with multivariate curve resolution (MCR) to the analysis of the constituents of commercial chocolate samples. The combination of different spectral data pretreatment methods allowed decreasing the high fluorescent Raman signal contribution of whey in the investigated chocolate samples. Using equality constraints during MCR analysis, estimations of the pure spectra of the chocolate sample constituents were improved, as well as their relative contributions and their spatial distribution on the analyzed samples. In addition, unknown constituents could be also resolved. White chocolate constituents resolved from Raman hyperspectral image indicate that, at macro scale, sucrose, lactose, fat, and whey constituents were intermixed in particles. Infrared hyperspectral imaging did not suffer from fluorescence and could be applied for white and milk chocolate. As a conclusion of this study, micro-hyperspectral imaging coupled to the MCR method is confirmed to be an appropriate tool for the direct analysis of the constituents of chocolate samples, and by extension, it is proposed for the analysis of other mixture constituents in commercial food samples. PMID- 26162694 TI - Molecular dynamics analysis of the transient temperature increase at void locations in shocked materials: RDX and Cu. AB - Molecular dynamics (MD) simulations of high velocity impact (1-6 km/s) of RDX crystal with a nanometer-sized void, has been carried out to understand the mechanism of increase in temperature at void locations under shock loading. Similar simulations are then carried out on single-crystal copper for better interpretation of the results. A reactive potential that can simulate chemical reactions (ReaxFF) has been used for RDX, whereas an EAM potential has been used for Cu. Increased temperature at the void locations are observed under shock loading. The atomic motion, temperature, average potential energy per atom (PE), and average kinetic energy per atom (KE) in and around the voids are closely monitored in order to understand the reason for temperature increase. We compare our results with existing proposed mechanisms and show that some of the proposed mechanisms are not necessary for increased temperature at a void location. It is shown that the directed particle velocity is efficiently is converted into randomized velocity due to the presence of voids thereby increasing the local temperature transiently. In this initial stage (few picoseconds) of the shock, chemical reactions of energetic materials do not play a part in the temperature rise. PMID- 26162692 TI - TLR4 antagonist attenuates atherogenesis in LDL receptor-deficient mice with diet induced type 2 diabetes. AB - Although a large number of studies have well documented a key role of toll-like receptor (TLR)4 in atherosclerosis, it remains undetermined if TLR4 antagonist attenuates atherogenesis in mouse model for type 2 diabetes. In this study, we induced type 2 diabetes in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice by high-fat diet (HFD). At 8 weeks old, 20 mice were fed HFD and 20 mice fed regular chow (RC) for 24 weeks. In the last 10 weeks, half HFD-fed mice and half RC-fed mice were treated with Rhodobacter sphaeroides lipopolysaccharide (Rs LPS), an established TLR4 antagonist. After the treatment, atherosclerotic lesions in aortas were analyzed. Results showed that the HFD significantly increased bodyweight, glucose, lipids including total cholesterol, triglycerides and free fatty acids, and insulin resistance, indicating that the HFD induced type 2 diabetes in LDLR(-/-) mice. Results also showed that Rs-LPS had no effect on HFD-increased metabolic parameters in both nondiabetic and diabetic mice. Lipid staining of aortas and histological analysis of cross-sections of aortic roots showed that diabetes increased atherosclerotic lesions, but Rs-LPS attenuated atherogenesis in diabetic mice. Furthermore, immunohistochemical studies showed that Rs-LPS reduced infiltration of monocytes/macrophages and expression of interleukin (IL)-6 and matrix metalloproteinase-9 in atherosclerotic lesions of diabetic mice. Finally, the antagonistic effect of Rs LPS on TLR4 was demonstrated by our in vitro studies showing that Rs-LPS inhibited IL-6 secretion from macrophages and endothelial cells stimulated by LPS or LPS plus saturated fatty acid palmitate. Taken together, our study demonstrated that TLR4 antagonist was capable of attenuating vascular inflammation and atherogenesis in mice with HFD-induced type 2 diabetes. PMID- 26162695 TI - Computational design of enzyme-ligand binding using a combined energy function and deterministic sequence optimization algorithm. AB - Enzyme amino-acid sequences at ligand-binding interfaces are evolutionarily optimized for reactions, and the natural conformation of an enzyme-ligand complex must have a low free energy relative to alternative conformations in native-like or non-native sequences. Based on this assumption, a combined energy function was developed for enzyme design and then evaluated by recapitulating native enzyme sequences at ligand-binding interfaces for 10 enzyme-ligand complexes. In this energy function, the electrostatic interaction between polar or charged atoms at buried interfaces is described by an explicitly orientation-dependent hydrogen bonding potential and a pairwise-decomposable generalized Born model based on the general side chain in the protein design framework. The energy function is augmented with a pairwise surface-area based hydrophobic contribution for nonpolar atom burial. Using this function, on average, 78% of the amino acids at ligand-binding sites were predicted correctly in the minimum-energy sequences, whereas 84% were predicted correctly in the most-similar sequences, which were selected from the top 20 sequences for each enzyme-ligand complex. Hydrogen bonds at the enzyme-ligand binding interfaces in the 10 complexes were usually recovered with the correct geometries. The binding energies calculated using the combined energy function helped to discriminate the active sequences from a pool of alternative sequences that were generated by repeatedly solving a series of mixed-integer linear programming problems for sequence selection with increasing integer cuts. PMID- 26162696 TI - Mitral paravalvular leak generating a Coanda effect inside the left atrium appendage. PMID- 26162697 TI - Clinical Recommendation: Labial Adhesions. AB - Labial adhesions, also known as labial agglutination, are a common finding in prepubertal adolescents. They are defined as fusion of the labia minora in the midline or are termed vulvar adhesions when they occur below the labia minora (inner labia). Patients are often asymptomatic but might present with genitourinary complaints. The decision for treatment is based on symptoms. The mainstay of treatment in asymptomatic patients is conservative, with careful attention to vulvar hygiene and reassurance to parents. In symptomatic patients, topical treatment with estrogen and/or steroid cream is often curative. Less often, corrective surgery is necessary. Recurrence is common until a patient goes through puberty. These recommendations are intended for pediatric and gynecologic health care providers who care for pediatric and adolescent girls to facilitate diagnosis and treatment. PMID- 26162698 TI - Placental expression of imprinted genes varies with sampling site and mode of delivery. AB - Imprinted genes, which are monoallelically expressed by virtue of an epigenetic process initiated in the germline, are known to play key roles in regulating fetal growth and placental development. Numerous studies are investigating the expression of these imprinted genes in the human placenta in relation to common complications of pregnancy such as fetal growth restriction and preeclampsia. This study aimed to determine whether placental sampling protocols or other factors such as fetal sex, gestational age and mode of delivery may influence the expression of imprinted genes predicted to regulate placental signalling. METHODS: Term placentas were collected from Caucasian women delivering at University Hospital of Wales or Royal Gwent Hospital within two hours of delivery. Expression of the imprinted genes PHLDA2, CDKN1C, PEG3 and PEG10 was assayed by quantitative real time PCR. Intraplacental gene expression was analysed (N = 5). Placental gene expression was compared between male (N = 11) and female (N = 11) infants, early term (N = 8) and late term (N = 10) deliveries and between labouring (N = 13) and non-labouring (N = 21) participants. RESULTS: The paternally expressed imprinted genes PEG3 and PEG10 were resilient to differences in sampling site, fetal sex, term gestational age and mode of delivery. The maternally expressed imprinted gene CDKN1C was elevated over 2-fold (p < 0.001) in placenta from labouring deliveries compared with elective caesarean sections. In addition, the maternally expressed imprinted gene PHLDA2 was elevated by 1.8 fold (p = 0.01) in samples taken at the distal edge of the placenta compared to the cord insertion site. CONCLUSION: These findings support the reinterpretation of existing data sets on these genes in relation to complications of pregnancy and further reinforce the importance of optimising and unifying placental collection protocols for future studies. PMID- 26162700 TI - Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats. AB - In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 umol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 umol) and cytidine (1.0 umol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 ug) and mecamylamine (50 ug) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 umol CDP choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels. PMID- 26162699 TI - Antinociceptive properties of selective MT(2) melatonin receptor partial agonists. AB - Melatonin is a neurohormone involved in the regulation of both acute and chronic pain whose mechanism is still not completely understood. We have recently demonstrated that selective MT2 melatonin receptor partial agonists have antiallodynic properties in animal models of chronic neuropathic pain by modulating ON/OFF cells of the descending antinociceptive system. Here, we examined the antinociceptive properties of the selective MT2 melatonin receptor partial agonists N-{2-[(3-methoxyphenyl)phenylamino]ethyl}acetamide (UCM765) and N-{2-[(3-bromophenyl)-(4-fluorophenyl)amino]ethyl}acetamide (UCM924) in two animal models of acute and inflammatory pain: the hot-plate and formalin tests. UCM765 and UCM924 (5-40 mg/kg, s.c.) dose-dependently increased the temperature of the first hind paw lick in the hot-plate test, and decreased the total time spent licking the injected hind paw in the formalin test. Antinociceptive effects of UCM765 and UCM924 were maximal at the dose of 20mg/kg. At this dose, the effects of UCM765 and UCM924 were similar to those produced by 200 mg/kg acetaminophen in the hot-plate test, and by 3 mg/kg ketorolac or 150 mg/kg MLT in the formalin test. Notably, antinociceptive effects of the two MT2 partial agonists were blocked by the pre-treatment with the MT2 antagonist 4-phenyl-2 propionamidotetralin (4P-PDOT, 10 mg/kg) in both paradigms. These results demonstrate the antinociceptive properties of UCM765 and UCM924 in acute and inflammatory pain models and corroborate the concept that MT2 melatonin receptor may be a novel target for analgesic drug development. PMID- 26162701 TI - Anti-inflammatory effects of farrerol on IL-1beta-stimulated human osteoarthritis chondrocytes. AB - The present study aimed to investigate the anti-inflammatory effects and the underlying molecular mechanism of farrerol on IL-1beta-stimulated human osteoarthritis chondrocytes. Chondrocytes were pretreated with farrerol 1h before IL-1beta stimulation. The effects of farrerol on NO and PGE2 production were tested by Griess reagent and ELISA. The effects of farrerol on COX-2, iNOS, Akt, phosphorylated Akt, and NF-kappaB activation were measured by western blot analysis. The results showed that farrerol remarkably inhibited IL-1beta-induced NO and PGE2 production, as well as COX-2 and iNOS expression. Farrerol also inhibited IL-1beta-induced NF-kappaB activation. Furthermore, farrerol significantly inhibited IL-1beta-induced phosphorylation of PI3K and Akt. In conclusion, these results indicated that farrerol inhibited IL-1beta-induced inflammatory responses in osteoarthritis chondrocytes by blocking PI3K/Akt/NF kappaB signaling pathway. PMID- 26162702 TI - Neuroprotective effects of the monoamine oxidase inhibitor tranylcypromine and its amide derivatives against Abeta(1-42)-induced toxicity. AB - Monoamine oxidase (MAO) enzymes play a central role in the pathogenesis of Alzheimer's disease (AD) and MAO inhibitors (MAOIs) are antidepressant drugs currently studied for their neuroprotective properties in neurodegenerative disorders. In the present work MAOIs such as tranylcypromine [trans-(+)-2 phenylcyclopropanamine, TCP] and its amide derivatives, TCP butyramide (TCP-But) and TCP acetamide (TCP-Ac), were tested for their ability to protect cortical neurons challenged with synthetic amyloid-beta (Abeta)-(1-42) oligomers (100 nM) for 48 h. TCP significantly prevented Abeta-induced neuronal death in a concentration-dependent fashion and was maximally protective only at 10 uM. TCP But was maximally protective in mixed neuronal cultures at 1 uM, a lower concentration compared to TCP, whereas the new derivative, TCP-Ac, was more efficacious than TCP and TCP-But and significantly protected cortical neurons against Abeta toxicity at nanomolar concentrations (100 nM). Experiments carried out with the Thioflavin-T (Th-T) fluorescence assay for fibril formation showed that TCP and its amide derivatives influenced the early events of the Abeta aggregation process in a concentration-dependent manner. TCP-Ac was more effective than TCP-But and TCP in slowing down the Abeta(1-42) aggregates formation through a lengthening at the lag phase. In our experimental model co incubation of Abeta(1-42) oligomers with TCP-Ac was able to almost completely prevent Abeta-induced neurodegeneration. These results suggest that inhibition of Abeta oligomer-mediated aggregation significantly contributes to the overall neuroprotective activity of TCP-Ac and also raise the possibility that TCP, and in particular the new compound TCP-Ac, might represent new pharmacological tools to yield neuroprotection in AD. PMID- 26162703 TI - Allele, phenotype and disease data at Mouse Genome Informatics: improving access and analysis. AB - A core part of the Mouse Genome Informatics (MGI) resource is the collection of mouse mutations and the annotation phenotypes and diseases displayed by mice carrying these mutations. These data are integrated with the rest of data in MGI and exported to numerous other resources. The use of mouse phenotype data to drive translational research into human disease has expanded rapidly with the improvements in sequencing technology. MGI has implemented many improvements in allele and phenotype data annotation, search, and display to facilitate access to these data through multiple avenues. For example, the description of alleles has been modified to include more detailed categories of allele attributes. This allows improved discrimination between mutation types. Further, connections have been created between mutations involving multiple genes and each of the genes overlapping the mutation. This allows users to readily find all mutations affecting a gene and see all genes affected by a mutation. In a similar manner, the genes expressed by transgenic or knock-in alleles are now connected to these alleles. The advanced search forms and public reports have been updated to take advantage of these improvements. These search forms and reports are used by an expanding number of researchers to identify novel human disease genes and mouse models of human disease. PMID- 26162704 TI - Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations. AB - We report paternally inherited duplication of 1q12q21.2 of 5.8 Mb associated with maternally inherited deletion of 16p11.2 of 545 Kb, this latter first identified in a fetus exhibiting an absent nasal bone detected during pregnancy. During the neonatal period, the young boy presented developmental delay, epilepsy, congenital anomalies and overweight. The clinical features of the proband with two rearrangements were more severe than in either of the parents carrying only one or the other mutation. Thus our data support a two-hit model in which the concomitant presence of these two copy-number variations exacerbates the neurodevelopmental phenotype. PMID- 26162705 TI - Predicting Changes Across 12 Months in Three Types of Parental Support Behaviors and Mothers' Perceptions of Child Physical Activity. AB - BACKGROUND: Parental support has been established as the critical family-level variable linked to child physical activity with encouragement, logistical support, and parent-child co-activity as key support behaviors. PURPOSE: This study aims to model these parental support behaviors as well as family demographics as mediators of mothers' perceptions of child physical activity using theory of planned behavior (TPB) across two 6-month waves of longitudinal data. METHOD: A representative sample of Canadian mothers (N = 1253) with children aged 5 to 13 years of age completed measures of TPB, support behaviors, and child physical activity. RESULTS: Autoregressive structural equation models showed that intention and perceived behavioral control explained support behaviors, yet child age (inverse relationship) and family income were independent predictors. The three support behaviors explained 19-42 % of the variance in child physical activity between participants, but analyses of change showed much smaller effects. CONCLUSIONS: Mothers' support behaviors are related to perceived child physical activity, but support is dependent on perception of control, child age, and family income. PMID- 26162706 TI - Root uptake and translocation of nickel in wheat as affected by histidine. AB - The role of histidine (His) on root uptake, xylem loading and root to shoot transport of nickel (Ni) was investigated in a winter (Triticum aestivum cv. Back Cross) and a durum wheat (Triticum durum cv. Durum) cultivar. Seedlings were grown in a modified Johnson nutrient solution and exposed to 10 MUM of Ni and 100 MUM of histidine (His) as no His, Ni (10) + His (100) and Ni(His) in a 1:1 mole ratio (1:1) complex. In our study, the presence of vanadate (a metabolic inhibitor) resulted in a significant decrease of root Ni uptake, indicating that a part of Ni uptake by the plant root is energy-dependent. Addition of His significantly increased the Ni content in shoots and roots of both wheat cultivars. The data suggest that the Ni(His) is most likely to be taken up as a complex or receptors at the membrane are able to enhance Ni uptake from Ni(His) complex. This result was indirectly supported by using EDTA as a strong chelating reagent to reduce the uptake of Ni(His) complexes. By using this ligand, the xylem loading of Ni and His was disproportionately reduced. Cycloheximide (a translation inhibitor) strongly decreased the release of His and Ni from the root into the xylem of wheat, suggesting the significance of a symplastic pathway for Ni loading into the xylem. PMID- 26162707 TI - Low contrast dose protocol involving a 100 kVp tube voltage for hypervascular hepatocellular carcinoma in patients with renal dysfunction. AB - PURPOSE: To evaluate the feasibility of a 20 % reduced contrast dose hepatic arterial phase (HAP) CT for hypervascular hepatocellular carcinoma (HCC) with 100 kVp. MATERIALS AND METHODS: The study included 97 patients with hypervascular HCC who underwent dynamic CT, including HAP scanning. The 54 patients had an estimated glomerular filtration rate (eGFR) of >=60 were scanned with our conventional 120 kVp protocol. The other 43 patients (eGFR < 60) underwent scans using a tube voltage of 100 kVp and a 20 % reduced contrast dose. We compared the estimated effective dose, image noise, tumor-liver contrast (TLC), and contrast to-noise ratio (CNR) in the hepatic arterial phase between the two groups using the Student's t test. RESULTS: Estimated effective dose and image noise were not significantly different between these groups (p = 0.67 and p = 0.20, respectively). The TLC and CNR were significantly higher for the 100 kVp protocol than for the 120 kVp protocol (52.2 HU +/- 17.4 vs 40.8 HU +/- 18.6, p < 0.01 and 6.8 +/- 2.6 vs 5.5 +/- 2.4, p = 0.01, respectively). CONCLUSION: For hepatic arterial phase CT of hypervascular HCC, 100 kVp scan allows a 20 % reduction in the contrast dose without reduction in image quality compared with a standard 120 kVp CT protocol. PMID- 26162708 TI - Benefits of an asthma education program provided at primary care sites on asthma outcomes. AB - BACKGROUND: Although it is a key-recommendation of all recent asthma guidelines, self-management education is still insufficiently offered in primary care settings. AIMS OF THE STUDY: To demonstrate the benefits of an educational program offered at the site of primary care (Family Medicine Clinics- FMC) by trained asthma educators on patient outcomes and healthcare use. METHODS: This was a one-year pre-post intervention study. Patients with a diagnosis of mild to moderate asthma were enrolled from six FMC. After an initial encounter by the educator, an assessment of educational needs and a spirometry were done, followed by 3 follow-up visits at 4-6 weeks, 4-6 months and one year. Expiratory flows, asthma control criteria, knowledge about asthma, adherence to medication and healthcare and medication use were assessed at each visit. RESULTS: Data from 124 asthma patients (41M/83F), aged 55 +/- 18 years, were analyzed. After initiating the intervention, there was a progressive increase in asthma knowledge and an improvement in medication adherence. The number of unscheduled visits for respiratory problems went from 137 to 33 (P < 0.0001), the number of antibiotic treatments from 112 to 33 (P = 0.0002) and the number of oral corticosteroids treatments from 26 to 8 (NS). Marked improvements were observed in regard to inhaler technique and provision of a written action plan. CONCLUSION: This study shows that an educational intervention applied at the site of primary care can result in significant improvements in patient asthma outcomes and reduce unscheduled visits and inappropriate use of medications such as antibiotics. PMID- 26162709 TI - Mast cell activation disease: An underappreciated cause of neurologic and psychiatric symptoms and diseases. AB - Neurologists and psychiatrists frequently encounter patients whose central and/or peripheral neurologic and/or psychiatric symptoms (NPS) are accompanied by other symptoms for which investigation finds no unifying cause and for which empiric therapy often provides little to no benefit. Systemic mast cell activation disease (MCAD) has rarely been considered in the differential diagnosis in such situations. Traditionally, MCAD has been considered as just one rare (neoplastic) disease, mastocytosis, generally focusing on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, MC activation syndrome (MC), has been recognized, featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. There also has developed greater appreciation for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory +/- allergic themes- including very wide arrays of central and peripheral NPS. Significantly helpful treatment--including for neuropsychiatric issues--usually can be identified once MCAD is accurately diagnosed. We describe MCAD's pathogenesis, presentation (focusing on NPS), and therapy, especially vis-a-vis neuropsychotropes. Since MCAD patients often present NPS, neurologists and psychiatrists have the opportunity, in recognizing the diagnostic possibility of MCAD, to short-circuit the often decades-long delay in establishing the correct diagnosis required to identify optimal therapy. PMID- 26162710 TI - Early single Aspirin-triggered Lipoxin blocked morphine anti-nociception tolerance through inhibiting NALP1 inflammasome: Involvement of PI3k/Akt signaling pathway. AB - Clinical usage of opioids in pain relief is dampened by analgesic tolerance after chronic exposure, which is related to opioid-associated neuroinflammation. In the current study, which is based on a chronic morphine tolerance rat model and sustained morphine treatment on primary neuron culture, it was observed that Akt phosphorylation, cleaved-Caspase-1-dependent NALP1 inflammasome activation and IL 1beta maturation in spinal cord neurons were significantly enhanced by morphine. Moreover, treatment with LY294002, a specific inhibitor of PI3k/Akt signaling, significantly reduced Caspase-1 cleavage, NALP1 inflammasome activation and attenuated morphine tolerance. Tail-flick tests demonstrated that pharmacological inhibition on Caspase-1 activation or antagonizing IL-1beta dramatically blocked the development of morphine tolerance. The administration of an exogenous analogue of lipoxin, Aspirin-triggered Lipoxin (ATL), caused a decline in Caspase 1 cleavage, inflammasome activation and mature IL-1beta production and thus attenuated the development of morphine tolerance by inhibiting upstream Akt phosphorylation. Additionally, treatment with DAMGO, a selective MU-opioid receptor peptide, significantly induced Akt phosphorylation, Caspase-1 cleavage and anti-nociception tolerance, all of which were attenuated by ATL treatment. Taken together, the present study revealed the involvement of spinal NALP1 inflammasome activation in the development of morphine tolerance and the role of the MU-receptor/PI3k-Akt signaling/NALP1 inflammasome cascade in this process. By inhibiting this signaling cascade, ATL blocked the development of morphine tolerance. PMID- 26162711 TI - Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection. AB - The incidence of autoimmune and inflammatory diseases has risen dramatically in post-industrial societies. "Biome depletion" - loss of commensal microbial and multicellular organisms such as helminths (intestinal worms) that profoundly modulate the immune system - may contribute to these increases. Hyperimmune associated disorders also affect the brain, especially neurodevelopment, and increasing evidence links early-life infection to cognitive and neurodevelopmental disorders. We have demonstrated previously that rats infected with bacteria as newborns display life-long vulnerabilities to cognitive dysfunction, a vulnerability that is specifically linked to long-term hypersensitivity of microglial cell function, the resident immune cells of the brain. Here, we demonstrate that helminth colonization of pregnant dams attenuated the exaggerated brain cytokine response of their offspring to bacterial infection, and that combined with post-weaning colonization of offspring with helminths (consistent with their mothers treatment) completely prevented enduring microglial sensitization and cognitive dysfunction in adulthood. Importantly, helminths had no overt impact on adaptive immune cell subsets, whereas exaggerated innate inflammatory responses in splenic macrophages were prevented. Finally, helminths altered the effect of neonatal infection on the gut microbiome; neonatal infection with Escherichia coli caused a shift from genera within the Actinobacteria and Tenericutes phyla to genera in the Bacteroidetes phylum in rats not colonized with helminths, but helminths attenuated this effect. In sum, these data point toward an inter-relatedness of various components of the biome, and suggest potential mechanisms by which this helminth might exert therapeutic benefits in the treatment of neuroinflammatory and cognitive disorders. PMID- 26162713 TI - Quantification of CSF biomarkers using an electrochemiluminescence-based detection system in the differential diagnosis of AD and sCJD. AB - The identification of reliable diagnostic tools for the differential diagnosis between sporadic Creutzfeldt-Jakob Disease (sCJD) and Alzheimer's disease (AD) remains impeded by the existing clinical, neuropathological and molecular overlap between both diseases. The development of new tools for the quantitative measurement of biomarkers is gaining experimental momentum due to recent advances in high-throughput screening analysis and with the optimization of assays for their quantification in biological fluids, including cerebrospinal fluid (CSF). Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve clinical quality performance in a variety of sample types due to its high sensitivity and dynamic range. Here, we quantified the CSF levels of Tau-protein, beta-amyloid 1-42 (Abeta42) and alpha-synuclein, as important biomarkers in CSF used in the differential diagnosis of neurodegenerative disorders in 12 AD, 12 sCJD and 12 control cases by singleplex ECL-based technology. Its performance has been compared to classical enzyme-linked immunosorbent assays (ELISA) to confront their clinical accuracy. ECL-based technology validates previous data obtained with ELISA and presents a higher performance in the discrimination of three analysed groups as determined by increased area under the curve (AUC) values for the three biomarkers. Importantly, alpha-synuclein levels detected by ECL allow an excellent discrimination between sCJD cases and AD and control cases, unveiling a new clinical approach for the differential diagnosis of sCJD. PMID- 26162714 TI - UNC13A confers risk for sporadic ALS and influences survival in a Spanish cohort. AB - To investigate the association of functional variants of the human UNC13A gene with the risk of ALS, survival and the disease progression rate in a Spanish ALS cohort. 136 sporadic ALS (sALS) patients and 487 healthy controls were genotyped for the UNC13A rs12608932 variant. Clinical characterization of ALS patients included gender, age at first symptom, initial topography, disease progression rate, and survival. Genetic association was analyzed under five inheritance models. The sALS patients with the rs12608932(CC) genotype had an increased risk of ALS under a recessive genetic model [OR 2.16; 95 % CI (1.23, 3.8), p = 0.009; corrected p = 0.028]. Genotypes with a C allele are also associated with increased risk [OR 1.47; 95 % CI (1.11, 1.95); p = 0.008; corrected p = 0.023] under an additive model. sALS patients with a C/C genotype had a shorter survival than patients with A/A and A/C genotypes [HR 1.44; 95 % CI (1.11, 1.873); p = 0.007] under a recessive model. In an overdominant model, heterozygous patients had a longer survival than homozygous patients [HR 0.36; 95 % CI (0.22, 0.59); p = 0.001]. The rs12608932 genotypes modify the progression of symptoms measured using the ALSFRS-R. No association with age of onset, initial topography or rate of decline in FVC was found. Our results show that rs12608932 is a risk factor for ALS in the Spanish population and replicate the findings described in other populations. The rs12608932 is a modifying factor for survival and disease progression rate in our series. Our results also corroborated that it did not influence the age of onset. PMID- 26162716 TI - Erratum to: Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome in a patient with the R232C TRPV4 mutation. PMID- 26162717 TI - Discontinued cardiovascular drugs in 2013 and 2014. AB - INTRODUCTION: Cardiovascular diseases (CVDs) are the number one cause of death globally. The dramatically high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention within the pharmaceutical industry. However, ~ 10,000 compounds are tested for every one drug that reaches the market. For this reason, it is helpful to recapitulate previous failures and learn from these experiences. AREAS COVERED: This paper focuses on the 10 cardiovascular drugs discontinued after reaching animal studies or Phase I - II clinical trials between 1 January 2013 and 31 December 2014. EXPERT OPINION: The trend of increasing numbers of cardiovascular drug development terminations seen in recent years has changed. Only 10 cardiovascular drugs were discontinued after reaching animal studies or Phase I - II clinical trials between 2013 and 2014. Only two candidates were discontinued in the Phase I clinical evaluation, and eight were discontinued during Phase II development. Most discontinuations were attributed to lack of efficacy and safety. One orphan drug (RTA-402) appeared in the list of discontinued cardiovascular drugs. The most eye-catching one of the 10 discontinued drugs is RG-7652, a monoclonal antibody against PCSK9, which is predicted as the next statin. PMID- 26162715 TI - Features of anti-aquaporin 4 antibody-seropositive Chinese patients with neuromyelitis optica spectrum optic neuritis. AB - The detection of anti-aquaporin-4 autoantibody (AQP-4 Ab) is crucial to detect patients who will develop neuromyelitis optica (NMO); however, there are few studies on the AQP-4 Ab serostatus of patients with neuromyelitis optica spectrum ON. We analyzed the clinical and paraclinical features of neuromyelitis optica spectrum ON patients in China according to the patients' AQP4-Ab serostatus. 125 patients with recurrent and bilateral ON with simultaneous attacks were divided into AQP-4 Ab-seropositive and -seronegative groups. Demographic, clinical, serum autoantibody data, connective tissue disorders (CTDs), visual performance were compared. A Visual Acuity (VA) of less than 0.1 during acute ON attacks occurred more frequently in the seropositive group (p = 0.023); however, there was not a significant difference between groups on VA recovery after the first attack. The seropositive group experienced the worst outcome during the last attack (p = 0.017). Other co-existing autoimmunity antibodies (p < 0.001) and CTDs (p < 0.001) were more prevalent in seropositive patients. There were no significant differences on VA recovery and RNFLT combined with other autoantibodies or CTDs. The two groups did not differ significantly with regard to time to relapse, annualized relapse rates, time of diagnosis NMO, or RNFL. There were no significant differences on VA recovery and RNFLT combined with other autoantibodies or CTDs. RNFLT was thinner in NMO seropositive patients. Although AQP-4 Ab expression predicted poor visual outcome, positive patients were usually associated with mild symptoms at first onset. Anti-SSA/SSB antibody or Sjogren syndrome may be associated with AQP-4 Ab in neuromyelitis optica spectrum ON. PMID- 26162719 TI - Improvements to a Grating-Based Spectral Imaging Microscope and Its Application to Reflectance Analysis of Blue Pen Inks. AB - A modified design of a chromatically resolved optical microscope (CROMoscope), a grating-based spectral imaging microscope, is described. By altering the geometry and adding a beam splitter, a twisting aberration that was present in the first version of the CROMoscope has been removed. Wavelength adjustment has been automated to decrease analysis time. Performance of the new design in transmission-absorption spectroscopy has been evaluated and found to be generally similar to the performance of the previous design. Spectral bandpass was found to be dependent on the sizes of apertures, and the smallest measured spectral bandpass was 1.8 nm with 1.0 mm diameter apertures. Wavelength was found to be very linear with the sine of the grating angle (R(2) = 0.9999995), and wavelength repeatability was found to be much better than the spectral bandpass. Reflectance spectral imaging with a CROMoscope is reported for the first time, and this reflectance spectral imaging was applied to blue ink samples on white paper. As a proof of concept, linear discriminant analysis was used to classify the inks by brand. In a leave-one-out cross-validation, 97.6% of samples were correctly classified. PMID- 26162720 TI - Differences in perception of gerotranscendence behaviors between college students and community-dwelling older adults. AB - Within the field of gerontology, several different theories have attempted to explain common psychological and social changes associated with the aging process. The Theory of Gerotranscendence is one such theory which purports that a shift in meta-perspective from a more materialistic and pragmatic view of the world to a more cosmic and transcendent one occurs as we age. Corresponding with this shift in meta-perspective, the individual exhibits certain behaviors that could be mistaken as signs of psychopathology if viewed based on the assumptions of more culturally-assimilated theories of aging. The purpose of this study was to examine the difference in perception of gerotranscendence behaviors between college students and older adults. Perceptions were quantified using an instrument that described many behaviors indicative of gerotranscendence within the context of a written narrative depicting an older adult living in an assisted living facility. Respondents were then asked to rate these behaviors in terms of how unusual they were and how concerning they were. As hypothesized, results indicated that several behaviors indicative of gerotranscendence were rated as more concerning and unusual by college students compared to older adults. Implications of these findings in terms of interactions between younger and older individuals occurring in the community and within healthcare settings are discussed. PMID- 26162721 TI - Embodying positive aging and neoliberal rationality: Talking about the aging body within narratives of retirement. AB - Within contemporary Western contexts, positive aging discourses are a key aspect of structured mandates for how to think about and act toward aging bodies. This study adds to previous work on embodiment that has situated how aging bodies are managed by focusing on the body as an aspect of retirement preparation, and critically considering how the imperative to govern the aging body in ways consistent with being a 'good' neoliberal citizen circulated through positive aging discourses is negotiated by aging individuals. Utilizing narrative data from a study addressing the discursive re-shaping and narrative negotiation of retirement within the Canadian context conducted with 30 informants aged 45 to 83, this paper draws upon a governmentality perspective to critically analyze ways informants talked about their aging bodies as part of preparing for and moving into retirement. Overall, the findings illustrate how informants embodied positive aging discourses and, in turn, embodied neoliberal rationality particularly in taking up the call to attend to the body as part of the broadening of retirement planning within a neoliberal context in which health, social, financial and other responsibilities are increasingly shifted toward individuals. Although informants described realizing some of the promises offered up with positive aging discourses, such as a sense of youthfulness and bodily control, their narratives also point to detrimental individual and social implications that can arise out of the limits of bodily practices, the need for perpetual risk management, an aversion to oldness, and attributions of failure. As such, this study raises concerns about the implications of the intersections of positive aging discourses and the neoliberal agenda of activation, responsibilization and individualization. PMID- 26162722 TI - Possession divestment by sales in later life. AB - Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers' capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation. Among this group, three-quarters of the households downsized by selling some belongings. Informal sales seemed the least fraught of all strategies, estate sales had mixed reviews, and garage sales were recalled as laborious. Sellers' efforts were eased by social relations and social networks as helpers and buyers came forward. As selling proceeded, sentiment about possessions waned as their materiality and economic value came to the fore, easing their detachment from the household. Possession selling is challenging because older adults are limited in the knowledge, skills, and efforts that they can apply to the recommodification of their belongings. Selling can nonetheless be encouraged as a divestment strategy as long as the frustrations and drawbacks are transparent, and the goal of ridding is kept in view. PMID- 26162723 TI - The distortions of care needs and medical professionalism: The ruling practices of migrant labor policy in Taiwan. AB - According to Taiwanese government policies and regulations, families planning to hire migrant care workers must apply for a medical assessment of the needs of elderly people destined to be cared for. The physician conducting this assessment acts as a gatekeeper who carries out her/his work with state and medical profession authority to identify, define, and regulate older people's needs. Using institutional ethnography as the method of inquiry, this article locates the problematic nature of the medical assessment as an entry point to an inquiry into how the care needs met by migrant workers are textually-mediated. This article begins by telling the daily story of an old woman and her live-in migrant worker to point out the standpoint of care recipients and their families where the inquiry anchors. I examine the physicians' daily working activities of medical assessment to discover how policy subordinates people's interests to the governmental purpose. PMID- 26162724 TI - "It was like reading a detective novel": Using PAR to work together for culture change. AB - Participatory action research (PAR), with its focus on engagement and collaboration, is uniquely suited to enhancing culture change initiatives in dementia care. Yet, there is limited literature of its application to culture change approaches in care settings, and even less in dementia specific care contexts. To address these gaps in the literature, the purpose of this paper is to examine the complexities of a PAR project aimed at changing the culture of dementia care in two diverse dementia care settings, including a long term care (LTC) and community care setting. Drawing from data gathered throughout the PAR process, we unpack the challenges experienced by participants working together to guide culture change within their respective care settings. These challenges include: overextending selves through culture change participation; fluctuating group membership; feeling uncertainty, confusion and apprehension about the process; frustratingly slow process; and seeking diverse group representation in decision making. We also highlight the potential for appreciative inquiry (AI) to be integrated with PAR to guide a process whereby participants involved in culture change initiatives can develop strategies to mitigate challenges they experience. We view the challenges and strategies shared here as being constructive to would-be culture change agents and hope this paper will move others to consider the use of PAR when engaging in culture change initiatives. PMID- 26162725 TI - Departure scripts and life review of parents living with abusive adult children with mental disorder. AB - BACKGROUND: Increasing numbers of aging parents are finding themselves in the role of caregiver for their mentally ill adult child due to global deinstitutionalization policy. The aim of this article is to explore preparations for the end of life in light of the life review process among old parents of abusive children with mental disorder. METHOD: Data collection was performed through in-depth semi-structured interviews with 20 parents, followed by phenomenological analysis. RESULTS: Five different types of departure scripts emerged: a pragmatic departure script, a burned-out departure script, a dead-end departure script, an optimistic departure script, and a violent departure script. CONCLUSION: The parents in this study tended to interpret events in their past to fit their perception of the current relationship with their child, thus connecting past, present, and future into one coherent picture. Years of extended care have led to a unique aging process which does not allow separation from the child or the development of a sense of closure that characterizes the aging process. This calls for better insights and deeper understanding in regard to intervention with such families. PMID- 26162726 TI - 'You don't show everyone your weakness': Older adults' views on using Family Group Conferencing to regain control and autonomy. AB - AIM: Family Group Conferencing (FGC), a model in which a person and his or her social network make their own 'care' plan, is used in youth care and might also be useful in elderly care to support older persons living at home. In Amsterdam, the Netherlands, FGC was implemented for older adults but they showed resistance. Reasons for this resistance have been researched and are described in this article. We examine existing views and attitudes of older adults concerning the use of FGC, and report on how older adults see the possibility to regain control over their lives using FGC. METHOD: To do this, focus group sessions, duo interviews and individual interviews were held with older adults with varying characteristics: living at home, in sheltered housing, or in a home for the elderly; and living in urban, suburban or rural areas. Themes were: views on and contentment with the control and autonomy that they experience in their lives, and the willingness to use FGC to improve this. RESULTS: The main reasons for our respondents to resist FGC were: expecting people to be there for them without a FGC, not feeling ready yet for a FGC, feeling embarrassed when asking for help, being reluctant to open up about their problems, and having the fear of losing control when organizing a FGC. We conclude that, for this generation of older adults, FGC means losing control and autonomy rather than gaining it. To be appealing to older adults, a relational empowerment strengthening model should most likely be focused on reciprocity, peer-to-peer support, and solutions instead of problems. PMID- 26162727 TI - The potential of Family Group Conferencing for the resilience and relational autonomy of older adults. AB - Family Group Conferencing (FGC) is emerging in the field of elderly care, as a method to enhance the resilience and relational autonomy of older persons. In this article, we want to explore the appropriateness of these two concepts to understand the FGC process in older adults. Using a case study design, we researched eight FGC cases for older adults, and selected two cases for further analysis and comparison. We found that the concepts of relational autonomy and resilience provide insight in the FGC process. Compassionately interfering social contacts, showing respect for the older person's needs and wishes gave older adults an impulse to take action to solve their problems. The capacity of a person to initiate and maintain social relations, and his or her willingness to ask for help, seemed essential to foster behavioral change. But apart from these, other, contextual factors seem to be important, which are currently not included in the theoretical framework for FGC, such as the nature of the problems, the involvement and capacities of the social network, and the older person's background. PMID- 26162728 TI - Baby boomers as future care users--An analysis of expectations in print media. AB - The aim of the study was to investigate media presentations of baby boomers as future care users. The Swedish baby boomer generation, born in the 1940s, and known as the '40s generation, has been characterized as youthful and powerful, and a question investigated in the study was whether boomers are supposed to display these characteristics as care users. We analyzed 481 articles in Swedish newspapers, published between 1995 and 2012, with a qualitative content analysis. The results showed that the '40s generation was predicted to become a new breed of demanding, self-aware care users. These claims were supported by descriptions of the formative events and typical characteristics of these individuals, which were then projected onto their future behavior as care users. Such projections tended to portray contemporary care users as passive, submissive, and partly responsible for problems associated with elder care. Consequently, approaches that focus on differences between cohorts need to incorporate a constructionist dimension to highlight the problem of generationism. PMID- 26162729 TI - Experiences of home and institution in a secured nursing home ward in The Netherlands: A participatory intervention study. AB - Nursing homes have been criticised for not providing a home for their residents. This article aims to provide insight into (1) the features of home and institution as experienced by residents and caregivers of a secured ward in a nursing home, and (2) how interventions implemented on the ward can contribute to a more home-like environment. For this purpose, a participatory intervention study, involving both caregivers and residents, was carried out. We collected data through qualitative research methods: observations, in-depth interviews and diaries to evaluate the interventions over time. We adopted an informed grounded theory approach, and used conceptualisations of total institutions and home as a theoretical lens. We found that the studied ward had strong characteristics of a total institution, such as batch living, block treatment and limited privacy. To increase the sense of home, interventions were formulated and implemented by the caregivers to increase the residents' autonomy, control and privacy. In this process, caregivers' perceptions and attitudes towards the provision of care shifted from task-oriented to person-centred care. We conclude that it is possible to increase the home-like character of a secured ward by introducing core values of home by means of interventions involving both caregivers and residents. PMID- 26162730 TI - The disaster flood experience: Older people's poetic voices of resilience. AB - This paper explores the experiences of older community-dwelling Australians evacuated from their homes during the 2011 and 2013 Queensland floods, applying the novel creative methodology of poetic inquiry as an analysis and interpretative tool. As well as exploring how older adults managed during a natural disaster, the paper documents the process and potential of poetic inquiry in gerontological research. The first and second poems highlight the different social resources older people have to draw on in their lives, especially during a crisis. Poem 1 ("Nobody came to help me") illustrates how one older resident felt all alone during the flood, whereas Poem 2 ("They came from everywhere"), Poem 3 ("The Girls") and Poem 5 ("Man in Blue Shirt") shows how supported--from both family and the wider community--other older residents felt. Poem 4 ("I can't swim") highlights one participant's fear as the water rises. To date, few studies have explicitly explored older adult's disaster experience, with this paper the first to utilise a poetic lens. We argue that poetic presentation enhances understanding of older residents' unique experiences during a disaster, and may better engage a wider audience of policy-makers, practitioners, the general community and older people themselves in discussion about, and reflection on, the impact and experience of disasters. PMID- 26162731 TI - Understanding welfare conditionality in the context of a generational habitus: A qualitative study of older citizens in England. AB - In many welfare states, 'austerity' policies have ignited debates about the fairness and cost-effectiveness of universal welfare benefits, with benefits received by older citizens a particular topic of concern. Empirical studies suggest that conditionality generates problems of access and uptake but, to date, there has been little research on how different conditions of entitlement are understood by older citizens. This study drew on interviews with 29 older citizens from three areas of England to explore how eligibility for and uptake of different kinds of welfare benefits were understood. In interviews, current entitlement was understood in relation to a generational habitus, in which 'our generation' was framed as sharing cohort experiences, and moral orientations to self-reliance, hard work and struggle. Entitlement to some welfare benefits was taken for granted as a reward owed by the state to its citizens for hard-earned lives. State transfers such as pensions, free travel and fuel subsidies were congruent with a nationalised generational habitus, and fostered recognition, self-worth and the sense of a generation as a collective. In contrast, transfers contingent on economic or need-based conditionality were more explicitly framed as 'benefits', and negatively associated with vulnerability and moral contestation. Uptake was therefore often incompatible with their generational habitus. Calls for introducing further conditionality to benefits for older adults are often based on claims that this will increase fairness and equality. Our analysis suggests, however, that introducing conditionality has the potential to promote inequality and foster differentiation and division, within the older population and between generations. PMID- 26162732 TI - Crafting citizen(ship) for people with dementia: How policy narratives at national level in Sweden informed politics of time from 1975 to 2013. AB - This article explores how policy narratives in national policy documents in Sweden inform associated politics on people with dementia. This is disentangled in terms of how people with dementia have been defined, what the problems and their imminent solutions have been, and if and how these have differed over time. Based on a textual analysis of policy documents at national level in Sweden, covering nearly 40 years the study shows how divergent policy narratives shape the construction of citizens with dementia as policy target groups. This study shows the temporal character of people with dementia as a political problem, the implications of policy narratives on people with dementia as a citizen group, and policy narratives as something being crafted rather than shaped by fixed pre existing "facts". Dementia, and further citizens living with dementia, does not have a once and for all stabilised meaning. Instead, the meanings behind the categories continue to evolve and to be crafted, which affects the construction of citizens living with dementia, the space in which to exercise their citizenship and further belonging to the society. PMID- 26162733 TI - "Blind people don't run": Escaping the "nursing home specter" in Children of Nature and Cloudburst. AB - The paper compares two films, Children of Nature (Born natturunnar, Iceland, Fridrik Por Fridriksson, 1991) and Cloudburst (Canada, Thom Fitzgerald, 2010), which share remarkable similarities, despite their difference in historical and geographical origin. In focusing on these two examples, the paper shows the extent to which a widespread fear of long-term residential care evident in popular discourse motivates larger commentaries about growing old. Each narrative presents a romance catalyzed by the threat of long-term residential care. In both stories, the couples are depicted as fugitives from the law, escaping what is perceived as a fate worse than death in order to pursue death on their own terms. The paper explores the structure and significance of how they leave and what they accomplish while they are away. The films offer examples of a broader cultural discourse that is damaging, while they are also heartening in their satisfying representation of the possibility of escape. Through that, they indicate the importance of choice and desire to transforming residential care in a manner that could also transform popular understandings of the "nursing home." PMID- 26162734 TI - Narrative care. Introduction. PMID- 26162735 TI - Cost-effectiveness of life-review for older adults with moderate depressive symptomatology: A pragmatic randomized controlled trial. AB - PURPOSE: Life-review has been established as an evidence-based treatment of depression in later life. This study investigates the cost-effectiveness of life review compared to care-as-usual. METHODS: An economic evaluation alongside a randomized controlled trial was carried out, comparing life-review (n=100) to care-as-usual (n=102). Individuals of 55 years and over, with moderate depressive symptomatology, were included. Treatment response was defined as a statistically reliable reduction of depressive symptoms on the Center for Epidemiologic Studies Depression scale. Total per-participant costs encompassed intervention costs, costs of receiving other treatments, participants' out-of-pocket expenses, and costs stemming from production losses, and were expressed in (2009) euros (?). RESULTS: At 6-month follow-up, treatment response was 54.0% and 27.5% in the life review and usual-care conditions, respectively. The difference in effectiveness was statistically significant at p=.001 (2-tailed). In the respective conditions the costs were ?5550 and ?3162, with the higher costs in the intervention arm of the trial. The incremental cost-effectiveness was ?8675 (US$10,227) per improved participant. CONCLUSION: The findings suggest that offering life-review rather than care-as-usual almost doubles the likelihood of a favorable outcome. However, the better clinical outcomes are achieved at greater costs. The conclusion that life-review offers good value for money is sensitive to the willingness to pay for a favorable treatment response. It is recommended that life-review is delivered by a single therapist and in larger groups as this may improve the cost effectiveness of this intervention. PMID- 26162736 TI - Narrative and resilience: A comparative analysis of how older adults story their lives. AB - Of increasing interest to gerontologists is resilience: the capacity for coping with the challenges of later life with openness and positivity. An overlooked factor in resilience, however, is the narrative complexity of older persons' self accounts. The research on which this article is based is part of a larger project aimed at assessing the role of narrative interventions in strengthening the stories that older people tell about their lives. Presented here are preliminary findings from analyses conducted by our multidisciplinary team (representing gerontology, social work, nursing, dementia studies, and literary theory) on open ended life story interviews done with 20 community-dwelling individuals (15 F, 5M; aged 65-89 years) who completed the Connor Davidson Resilience Scale. Specifically, we compared the self-accounts of the 6 from these 20 who scored highest on the CDRS with the 7 who scored lowest to determine any patterns in how each group "stories" their lives. We conclude with certain observations of relevance to narrative care. PMID- 26162737 TI - "Shadow stories" in oral interviews: Narrative care through careful listening. AB - In most narrative approaches to understanding old age, the primary object of interest is the told story. However, what is often overlooked in narrative research are the untold stories--the silences, gaps, and omissions that form a type of shadow story or a story that lies just below the surface of what is said or written. This paper presents an illustrative case example of Constance to demonstrate how careful listening can help uncover hidden stories in an interview. In this case, Constance mentions two people (her brother and husband) as being important in her life yet omits them from the majority of her interview. The interviewer is able to uncover a hidden story with regard to her brother, learning important details about their relationship that would have otherwise gone unspoken. Overall, findings point to the importance of untold stories both in terms of content and as a way to empower the speaker to address topics that he or she may have otherwise thought were not of interest to the interviewer. PMID- 26162738 TI - Narratives of nostalgia in the face of death: The importance of lighter stories of the past in palliative care. AB - My research on the stories of palliative care patients emphasizes the heterogeneity of the types of stories they tell, including stories of illness, of everyday life, of the future, and of the past (Synnes, 2012). This article pays special attention to the prevalence of stories of past experiences in which the past is portrayed through idyllic and nostalgic interpretation. In contrast to most research on illness narratives and narrative gerontology that is preoccupied with stories of change, these stories of nostalgia are characterized by a plot where nothing in particular happens. However, this may be the primary purpose for the storytellers in their particular situation of illness and imminent death. The main purpose of nostalgia is precisely to ensure the continuity of identity in the face of adversity (Davis, 1979). In this article, I argue that these stories of nostalgia are vital aspects of maintaining the continuity of the self, or a narrative identity, when much else in life is characterized by discontinuity and uncertainty. Thus, stories of nostalgia should not be dismissed as escapism but valued and listened to as important aspects of narrative care among palliative care patients, and as a way of preserving the sense of a narrative identity. PMID- 26162739 TI - Emerging themes in using narrative in geriatric care: Implications for patient centered practice and interprofessional teamwork. AB - Narrative approaches are increasingly used with older adults by different health professionals in a variety of care settings to provide unique and powerful insights into the patient's lifeworld and the meaning of their illness. Understanding these approaches requires insight into the narratives of both the patient and the provider. Different health professions have differing attitudes toward aging and are socialized into distinct ways of framing the problems of older adults. In a patient assessment, they may co-construct different stories that create the basis for interprofessional collaboration, posing challenges for communication among members of the team. This paper develops a conceptual framework for characterizing the use of narrative as the development of sets of "voices" reflecting a dynamic interaction between the provider and the patient, including the use of master narratives, stories and counterstories, and plots and subplots. The literature on the use of narrative with older adults in the professions of medicine, nursing, and social work is reviewed comparatively to develop a typology of these professional differences and the basis for them. Implications and recommendations for the development of new models of patient centered care and interprofessional practice with older adults are developed. PMID- 26162740 TI - Narrative ethics for narrative care. AB - Narrative permeates health care--from patients' stories taken as medical histories to the development of health policy. The narrative approach to health care has involved the move from narratives in health care as objects of study to the lens through which health care is studied and, more recently, to narrative as a form of care. In this paper, I argue that narrative care requires a move in the field of ethics--from a position where narratives are used to inform ethical decision making to one in which narrative is the form and process of ethical decision making. In other words, I argue for a narrative ethics for narrative care. The argument is relatively straightforward. If, as I argue, humans are narrative beings who make sense of themselves, others, and the world in and through narrative, we need to see our actions as both narratively based and narratively contextual and thus understanding the nature, form, and content of the narratives of which we are a part, and the process of narrativity, provides an intersubjective basis for ethical action. PMID- 26162741 TI - Narrative accountability and quality awareness: Learning about (re)presenting narrative care. AB - Over the years, the dominant accountability structures for eldercare in the Netherlands have conceptualized "care" in mainly quantitative terms, based on measurable outcomes and performance indicators. This article describes a two-year program that was designed to find ways for a renewed story of accountability and quality with a more "story conscious" way of engaging with the realities of both life and care. From the autoethnographical stance of the program manager, the article first provides the historical background of the program, tracing its roots in narrative gerontology. Second, it outlines the design of the program, which was meant to combine the practice of care organizations with scientific research and policy making. Third, it sheds light on issues of quality and accountability when eldercare is approached as a social constructionist practice. It concludes with some thoughts on how the learning gained in setting up the program are relevant to future policies regarding quality and accountability in eldercare. PMID- 26162742 TI - Understanding public elderly care policy in Norway: A narrative analysis of governmental White papers. AB - How the general public in Norway conceives being an older adult and the meaning of chronological age has changed over the last few decades. As narratives of aging may be identified in the Norwegian mass media and in the population at large, dominant narratives may also be identified in policy documents, such as government health policy papers. This article explores a narrative analytical framework based on stories, subtexts, and counterstories; it argues that such narratives are characterized as much by what is unsaid as by what is said, and as much by choice of words and word combinations as by explicit messages. Culture strongly influences the conception of a likely future (what will be) and an envisioned future (what ought to be) regarding aging and geriatric care in Norway, as expressed in the public policy papers. The public policy story is discussed as both a story continuously developing, where later health policy papers relate to and comment on earlier documents, and as a story characterized by a measure of cultural incoherence. Some recent government documents dealing with professional geriatric care will serve as material for a narrative analysis. PMID- 26162743 TI - Total synthesis of Lewis(X) using a late-stage crystalline intermediate. AB - Herein, we report on a highly efficient synthesis of a crystalline protected Lewis(X) trisaccharide that was converted to Lewis(X) following global deprotection. The trisaccharide was prepared in a highly convergent synthesis (seven steps, longest linear sequence) and in a 38% overall yield using a strategy that involved the regioselective glycosylation of a GlcNAc acceptor with a galactose thioglycoside donor, followed by fucosylation of the remaining free GlcNAc hydroxyl as key steps. The core trisaccharide also has the potential to be converted to other members of the Type-2 Lewis family of antigens due to the orthogonal nature of the protecting groups employed. PMID- 26162744 TI - UDP-hexose 4-epimerases: a view on structure, mechanism and substrate specificity. AB - UDP-sugar 4-epimerase (GalE) belongs to the short-chain dehydrogenase/reductase (SDR) superfamily of proteins and is one of enzymes in the Leloir pathway. They have been shown to be important virulence factors in a number of Gram-negative pathogens and to be involved in the biosynthesis of different polysaccharide structures. The metabolic disease type III galactosemia is caused by detrimental mutations in the human GalE. GalE and related enzymes display unusual enzymologic, chemical, and stereochemical properties; including irreversible binding of the cofactor NAD and uridine nucleotide-induced activation of this cofactor. These epimerases have been found active on UDP-hexoses, the N acetylated and uronic acid forms thereof as well as UDP-pentoses. As they are involved in different pathways and functions, a deeper understanding of the enzymes, and their substrate promiscuity and/or selectivity, could lead to drug and vaccine design as well as antibiotic and probiotic development. This review summarizes the research performed on UDP-sugar 4-epimerases' structure, mechanism and substrate promiscuity. PMID- 26162745 TI - Modeling of cooked starch digestion process using recombinant human pancreatic alpha-amylase and maltase-glucoamylase for in vitro evaluation of alpha glucosidase inhibitors. AB - In human, digestion of cooked starch mainly involves breaking down of alpha amylase to alpha-limit dextrins and small linear malto-oligosaccharides, which are in turn hydrolyzed to glucose by the gut mucosal maltase-glucoamylase (MGAM). Human pancreatic alpha-amylase (HPA), amino- and carboxyl-terminal portions of MGAM (ntMGAM and ctMGAM) catalyze the hydrolysis of alpha-D-(1,4) glycosidic linkages in starch, playing a crucial role in the production of glucose in the human lumen. Accordingly, these enzymes are effective drug targets for the treatments of type 2 diabetes and obesity. In this study, a Plackett-Burman based statistical screening procedure was adopted to determine the most critical factors affecting cooked starch digestion by the combination of HPA, ctMGAM and ntMGAM. Six factors were tested and experimental results showed that pH and temperature were the major influencing factors, with optimal pH and temperature at 6.0 and 50 degrees C, respectively. Surprisingly, ntMGAM had no significant contribution to the glucose production from starch digestion compared to the HPA and ctMGAM. The optimal proportion of HPA and ctMGAM in a starch digestion system was further determined by response surface methodology. Results showed a maximum starch digestion (88.05%) within 0.5 h when used HPA:ctMGAM=1:9 (U). The inhibitory effects of various inhibitors on the cooked starch digestion by HPA1/ctMGAM9 were evaluated by determining their half maximal inhibitory concentration (IC50) values. Acarviostatin II03 showed the highest inhibitory activity, with 67 times higher potency than acarbose. Moreover, acarviostatin II03 could significantly depress postprandial blood glucose levels in mice, better than that by acarbose. These findings suggest that our in vitro enzymatic system can simulate in vivo starch digestion process, and thus can be used to screen and evaluate alpha-glucosidase inhibitors. PMID- 26162746 TI - The influence of aerobic fitness on obesity and its parent-offspring correlations in a cross-sectional study among German families. AB - BACKGROUND: Overweight/obesity is an important public health burden worldwide, increasing the risk for the development of cardiovascular diseases or the metabolic syndrome. This risk may be reduced by a good aerobic fitness (AF) that can be improved by physical activity but is also influenced by genetic factors. The aim of this study was to test for familial aggregation of AF measured by maximal oxygen uptake (VO2max) and to estimate its heritability. Furthermore, an exploratory analysis of the association between overweight/obesity and AF was performed. In contrast to previous studies, all analyses were adjusted for additional environmental and behavioral factors, in particular for objectively measured physical activity (PA) in addition to body mass index (BMI). METHODS: 79 families (157 parents, 132 children) performed a maximum exercise test (spiroergometry) to assess maximum oxygen uptake. PA was measured by accelerometry. Familial aggregation of AF was determined using a two-step design: AF was adjusted for age, sex and age*sex using linear regression. Afterwards, the residuals were used to determine the intraclass correlation coefficient (ICC) by ANOVA. Heritability and associations were estimated by generalized linear mixed models. RESULTS: Familial aggregation of AF (ICC = 0.22, p < 0.001) was significant but decreased when adjusted for PA or BMI. Its heritability was estimated as 40% (adjusted for PA) using the mid-parent-offspring design. Relative to the middle quintile of AF residuals, the odds of being overweight/obese were three- to tenfold reduced in the upper quintile (adjusted for age, sex, age*sex, PA). CONCLUSIONS: AF clustered in families after controlling for PA, BMI and parental smoking. Heritability was stronger for mother-child pairs as compared to father-child pairs after controlling for PA and BMI. Above average AF was negatively associated with overweight/obesity. PMID- 26162747 TI - De novo assembly of a transcriptome from juvenile blue crabs (Callinectes sapidus) following exposure to surrogate Macondo crude oil. AB - BACKGROUND: The blue crab, Callinectes sapidus, is economically and ecologically important in western Atlantic and Gulf of Mexico coastal estuaries. In 2010 blue crabs in the northern Gulf of Mexico were exposed to crude oil and chemical dispersants from the Deepwater Horizon oil spill. To characterize the blue crab transcriptome and identify genes that could be regulated in response to oil exposure we sequenced transcriptomes from hepatopancreas and gill tissues of juvenile blue crabs after exposing them to a water-accommodated fraction of surrogate Macondo crude oil in the laboratory and compared them to transcriptomes from an unexposed control group. RESULTS: Illumina sequencing provided 42.5 million paired-end sequencing reads for the control group and 44.9 million paired end reads for the treatment group. From these, 73,473 transcripts and 52,663 genes were assembled. Comparison of control and treatment transcriptomes revealed about 100 genes from each tissue type that were differentially expressed. However, a much larger number of transcripts, approximately 2000 from each tissue type, were differentially expressed. Several examples of alternatively spliced transcripts were verified by qPCR, some of which showed significantly different expression patterns. The combined transcriptome from all tissues and individuals was annotated to assign putative gene products to both major gene ontology categories as well as specific roles in responses to cold and heat, metabolism of xenobiotic compounds, defence, hypoxia, osmoregulation and ecdysis. Among the annotations for upregulated and alternatively-spliced genes were candidates for the metabolism of oil-derived compounds. CONCLUSIONS: Previously, few genomic resources were available for blue crabs or related brachyuran crabs. The transcriptome sequences reported here represent a major new resource for research on the biology of blue crabs. These sequences can be used for studies of differential gene expression or as a source of genetic markers. Genes identified and annotated in this study include candidates for responses of the blue crab to xenobiotic compounds, which could serve as biomarkers for oil exposure. Changes in gene expression also suggest other physiological changes that may occur as the result of exposure to oil. PMID- 26162748 TI - Attitudes toward inter-hospital electronic patient record exchange: discrepancies among physicians, medical record staff, and patients. AB - BACKGROUND: In this era of ubiquitous information, patient record exchange among hospitals still has technological and individual barriers including resistance to information sharing. Most research on user attitudes has been limited to one type of user or aspect. Because few analyses of attitudes toward electronic patient records (EPRs) have been conducted, understanding the attitudes among different users in multiple aspects is crucial to user acceptance. This proof-of-concept study investigated the attitudes of users toward the inter-hospital EPR exchange system implemented nationwide and focused on discrepant behavioral intentions among three user groups. METHODS: The system was designed by combining a Health Level 7-based protocol, object-relational mapping, and other medical informatics techniques to ensure interoperability in realizing patient-centered practices. After implementation, three user-specific questionnaires for physicians, medical record staff, and patients were administered, with a 70 % response rate. The instrument showed favorable convergent construct validity and internal consistency reliability. Two dependent variables were applied: the attitudes toward privacy and support. Independent variables comprised personal characteristics, work characteristics, human aspects, and technology aspects. Major statistical methods included exploratory factor analysis and general linear model. RESULTS: The results from 379 respondents indicated that the patients highly agreed with privacy protection by their consent and support for EPRs, whereas the physicians remained conservative toward both. Medical record staff was ranked in the middle among the three groups. The three user groups demonstrated discrepant intentions toward privacy protection and support. Experience of computer use, level of concerns, usefulness of functions, and specifically, reason to use electronic medical records and number of outpatient visits were significantly associated with the perceptions. Overall, four categories of independent variables were associated with the mean difference in the perceptions. CONCLUSIONS: Discrepant attitudes toward privacy and support among the three user groups are identified. Patients may require further education and communication regarding the system. Culturally fit e-Consent should be incorporated into the system to fully utilize the computing power of the Internet when also considering workload. The concern for misuse of EPRs might lead to low support among physicians. Highly readable EPR documents and managerial incentives for information exchange may improve system use. PMID- 26162749 TI - The changing roles of registered nurses in Pioneer Accountable Care Organizations. AB - OBJECTIVES: This study focuses on whether and how Pioneer Accountable Care Organization (ACO) leaders believe the deployment of the registered nurse workforce is changing in response to the shared savings incentives. METHODS: Semistructured phone interviews with leaders from 18 of the original 32 Pioneer ACOs were conducted. RESULTS: Narrative analysis suggests that all of the organizations are developing new and enhanced roles for registered nurses across the continuum of care. Overall, eight types of changes were reported: enhancement of roles, substitution, delegation, increased numbers of nurses, relocation of services, transfer of nurses from one setting to another, the use of liaison nurses across settings, and partnerships between nurses coordinating care in primary and acute care settings. CONCLUSIONS: This exploratory study suggests that Pioneer ACO leaders believe that payment models are affecting the deployment of the health workforce and that these changes are, in turn, driving outcomes. PMID- 26162750 TI - Health care provider social network analysis: A systematic review. AB - OBJECTIVES: Although considerable progress has been made in understanding networks, their structure, and their development, little has been known about their effectiveness in the health care setting and their contributions to quality of care and patient safety.The purpose of this study was to examine studies using social network analysis (SNA) in the health care workforce and assess factors contributing to social network and their relationships with care processes and patient outcomes. METHODS: We identified all published peer-reviewed SNA articles in CINAHL, PubMed, PsycINFO, JSTOR, Medline (OVID), and Web of Science databases up to April 2013. RESULTS: Twenty-nine published articles met the inclusion criteria. Current evidence of the health care workforce's social networks reveals the nature of social ties are related to personal characteristics, practice setting, and types of patients. A few studies also revealed the social network effects adoption and the use of a health information system, patient outcomes, and coordination. CONCLUSIONS: Current studies on the social ties of health care workforce professionals include several assessments of inefficiencies. The level of technical sophistication in these studies tended to be low. Future study using enhanced sophistication in study design, analysis, and patient outcome testing are warranted to fully leverage the potential of SNA in health care studies. PMID- 26162752 TI - Response properties of neurons in the cat's putamen during auditory discrimination. AB - The striatum integrates diverse convergent input and plays a critical role in the goal-directed behaviors. To date, the auditory functions of striatum are less studied. Recently, it was demonstrated that auditory cortico-striatal projections influence behavioral performance during a frequency discrimination task. To reveal the functions of striatal neurons in auditory discrimination, we recorded the single-unit spike activities in the putamen (dorsal striatum) of free-moving cats while performing a Go/No-go task to discriminate the sounds with different modulation rates (12.5 Hz vs. 50 Hz) or envelopes (damped vs. ramped). We found that the putamen neurons can be broadly divided into four groups according to their contributions to sound discrimination. First, 40% of neurons showed vigorous responses synchronized to the sound envelope, and could precisely discriminate different sounds. Second, 18% of neurons showed a high preference of ramped to damped sounds, but no preference for modulation rate. They could only discriminate the change of sound envelope. Third, 27% of neurons rapidly adapted to the sound stimuli, had no ability of sound discrimination. Fourth, 15% of neurons discriminated the sounds dependent on the reward-prediction. Comparing to passively listening condition, the activities of putamen neurons were significantly enhanced by the engagement of the auditory tasks, but not modulated by the cat's behavioral choice. The coexistence of multiple types of neurons suggests that the putamen is involved in the transformation from auditory representation to stimulus-reward association. PMID- 26162751 TI - Brain-controlled functional electrical stimulation therapy for gait rehabilitation after stroke: a safety study. AB - BACKGROUND: Many stroke survivors have significant long-term gait impairment, often involving foot drop. Current physiotherapies provide limited recovery. Orthoses substitute for ankle strength, but they provide no lasting therapeutic effect. Brain-computer interface (BCI)-controlled functional electrical stimulation (FES) is a novel rehabilitative approach that may generate permanent neurological improvements. This study explores the safety and feasibility of a foot-drop-targeted BCI-FES physiotherapy in chronic stroke survivors. METHODS: Subjects (n = 9) operated an electroencephalogram-based BCI-FES system for foot dorsiflexion in 12 one-hour sessions over four weeks. Gait speed, dorsiflexion active range of motion (AROM), six-minute walk distance (6MWD), and Fugl-Meyer leg motor (FM-LM) scores were assessed before, during, and after therapy. The primary safety outcome measure was the proportion of subjects that deteriorated in gait speed by >=0.16 m/s at one week or four weeks post-therapy. The secondary outcome measures were the proportion of subjects that experienced a clinically relevant decrease in dorsiflexion AROM (>=2.5 degrees ), 6MWD (>=20 %), and FM-LM score (>=10 %) at either post-therapy assessment. RESULTS: No subjects (0/9) experienced a clinically significant deterioration in gait speed, dorsiflexion AROM, 6MWT distance, or FM-LM score at either post-therapy assessment. Five subjects demonstrated a detectable increase (>=0.06 m/s) in gait speed, three subjects demonstrated a detectable increase (>=2.5 degrees ) in dorsiflexion AROM, five subjects demonstrated a detectable increase (>=10 %) in 6MWD, and three subjects demonstrated a detectable increase (>=10 %) in FM-LM. Five of the six subjects that exhibited a detectable increase in either post-therapy gait speed or 6MWD also exhibited significant (p < 0.01 using a Mann-Whitney U test) increases in electroencephalogram event-related synchronization/desynchronization. Additionally, two subjects experienced a clinically important increase (>=0.16 m/s) in gait speed, and four subjects experienced a clinically important increase (>=20 %) in 6MWD. Linear mixed models of gait speed, dorsiflexion AROM, 6MWD, and FM-LM scores suggest that BCI-FES therapy is associated with an increase in lower motor performance at a statistically, yet not clinically, significant level. CONCLUSION: BCI-FES therapy is safe. If it is shown to improve post-stroke gait function in future studies, it could provide a new gait rehabilitation option for severely impaired patients. Formal clinical trials are warranted. PMID- 26162753 TI - Donepezil increases contrast sensitivity for the detection of objects in scenes. AB - We assessed the effects of donepezil, a drug that stimulates cholinergic transmission, and scopolamine, an antagonist of cholinergic transmission, on contrast sensitivity. 30 young male participants were tested under three treatment conditions: placebo, donepezil, and scopolamine in a random order. Pairs of photographs varying in contrast were displayed left and right of fixation for 50 ms. Participants were asked to locate the scene containing an animal. Accuracy was better under donepezil than under scopolamine, particularly for signals of high intensity (at higher levels of contrast). A control experiment showed that the lower performance under scopolamine did not result from the mydriasis induced by scopolamine. The results suggest that cholinergic stimulation, through donepezil, facilitates signal detection in agreement with studies on animals showing that the pharmacological activation of cholinergic receptors controls the gain in the relationship between the stimulus contrast (intensity of the visual input) and visual response. As Alzheimer disease is associated to depletion in acetylcholine, and there is evidence of deficits in contrast sensitivity in Alzheimer, it might be interesting to integrate such rapid and sensitive visual tasks in the biomarkers at early stage of drug development. PMID- 26162754 TI - Maternal bonding in childhood moderates autonomic responses to distress stimuli in adult males. AB - Mother-child bonding influences the development of cognitive and social skills. In this study we investigate how maternal attachment, developed in early childhood, modulates physiological responses to social stimuli later in life. Our results suggest that the autonomic nervous system's responses to vocal distress are moderated by the quality of participants' maternal bonding. In particular, participants with optimal maternal bonding showed a greater calming response to distressful stimuli whereas participants with non-optimal maternal bonding showed a heightened distress response. PMID- 26162755 TI - Separation of overlapping dental arch objects using digital records of illuminated plaster casts. AB - BACKGROUND: Plaster casts of individual patients are important for orthodontic specialists during the treatment process and their analysis is still a standard diagnostical tool. But the growing capabilities of information technology enable their replacement by digital models obtained by complex scanning systems. METHOD: This paper presents the possibility of using a digital camera as a simple instrument to obtain the set of digital images for analysis and evaluation of the treatment using appropriate mathematical tools of image processing. The methods studied in this paper include the segmentation of overlapping dental bodies and the use of different illumination sources to increase the reliability of the separation process. The circular Hough transform, region growing with multiple seed points, and the convex hull detection method are applied to the segmentation of orthodontic plaster cast images to identify dental arch objects and their sizes. RESULTS: The proposed algorithm presents the methodology of improving the accuracy of segmentation of dental arch components using combined illumination sources. Dental arch parameters and distances between the canines and premolars for different segmentation methods were used as a measure to compare the results obtained. CONCLUSION: A new method of segmentation of overlapping dental arch components using digital records of illuminated plaster casts provides information with the precision required for orthodontic treatment. The distance between corresponding teeth was evaluated with a mean error of 1.38% and the Dice similarity coefficient of the evaluated dental bodies boundaries reached 0.9436 with a false positive rate [Formula: see text] and false negative rate [Formula: see text]. PMID- 26162756 TI - Breakdown of bioenergetics evoked by mitochondrial damage in acute pancreatitis: Mechanisms and consequences. AB - Acute pancreatitis is a severe inflammatory disease with unacceptably high mortality and without specific therapy. Clinical studies revealed that energy supplementation of patients via enteral feeding decreases systemic infections, multi-organ failure and mortality. These clinical observations have been supported by in vitro and in vivo experimental studies which showed that the most common pancreatitis inducing factors, such as bile acids, ethanol and non oxidative ethanol metabolites induce intracellular ATP depletion and mitochondrial damage both in pancreatic acinar and ductal cells. Notably, the in vitro supplementation of ATP prevented the cellular damage and restored cell functions in both cell types. These observations suggest that either prevention of mitochondrial damage or restoration of intracellular ATP level might provide therapeutical benefits. PMID- 26162757 TI - Efficacy of anti-TNF alpha in severe and/or refractory Behcet's disease: Multicenter study of 124 patients. AB - OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behcet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 +/- 0.5 vs 1.7 +/- 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab). PMID- 26162759 TI - An investigation of cortical neuroplasticity following stroke in adults: is there evidence for a critical window for rehabilitation? AB - BACKGROUND: Evidence in animal stroke models suggests that neuroplasticity takes place maximally in a specific time window after an ischaemic lesion, which may coincide with the optimal time to intervene with rehabilitation. The aim of this study is to investigate neurophysiological evidence for a "critical window" of enhanced neuroplasticity in patients following ischaemic stroke, and establish its duration. We will also investigate changes in cortical inhibition following stroke, and the influence this has on functional recovery. METHODS/DESIGN: We will recruit participants recently admitted to the Stroke Unit of major metropolitan hospitals who have had a stroke and can provide informed consent. Participants will be excluded if they have any contraindications to Transcranial Magnetic Stimulation. We will compare neurophysiological outcomes in an age matched healthy control group. We conservatively hypothesise a 5% increase in neuroplasticity at the optimal timing following stroke, compared to control participants, and require 43 patients following stroke to detect a significant difference with 80% power. The primary outcome is the change in the motor evoked potential (MEP) amplitude in a hand muscle, after the administration of a plasticity-inducing paradigm to the affected hemisphere. Secondary outcomes include measures of cortical excitability, intracortical inhibition and arm function. DISCUSSION: The data from this trial will clarify whether there is a critical window for neuroplastic change in the brain following stroke. If so, intensive rehabilitation during this period could be more effective, reducing long-term disability and the cost burden of stroke. PMID- 26162758 TI - Distinct and synergistic roles of FcgammaRIIB deficiency and 129 strain-derived SLAM family proteins in the development of spontaneous germinal centers and autoimmunity. AB - The inhibitory IgG Fc receptor (FcgammaRIIB) deficiency and 129 strain-derived signaling lymphocyte activation molecules (129-SLAMs) are proposed to contribute to the lupus phenotype in FcgammaRIIB-deficient mice generated using 129 ES cells and backcrossed to C57BL/6 mice (B6.129.RIIBKO). In this study, we examine the individual contributions and the cellular mechanisms by which FcgammaRIIB deficiency and 129-derived SLAM family genes promote dysregulated spontaneous germinal center (Spt-GC) B cell and follicular helper T cell (Tfh) responses in B6.129.RIIBKO mice. We find that B6 mice congenic for the 129-derived SLAM locus (B6.129-SLAM) and B6 mice deficient in FcgammaRIIB (B6.RIIBKO) have increased Spt GC B cell responses compared to B6 controls but significantly lower than B6.129.RIIBKO mice. These data indicate that both FcgammaRIIB deficiency and 129 SLAMs contribute to elevated Spt-GC B cell responses in B6.129.RIIBKO mice. However, only 129-SLAMs contribute significantly to augmented Tfh responses in B6.129.RIIBKO mice, and do so by a combination of T cell-dependent effects and enhanced B cell and DC-dependent antigen presentation to T cells. Elevated Spt-GC B cell responses in mice with FcgammaRIIB deficiency and polymorphic 129-SLAMs were associated with elevated metabolic activity, improved GC B cell survival and increased differentiation of naive B cells into GC B cell phenotype. Our data suggest that the interplay between 129-SLAM expression on B cells, T cells and DCs is central to the alteration of the GC tolerance checkpoint, and that deficiency of FcgammaRIIB on B cells is necessary to augment Spt-GC responses, pathogenic autoantibodies, and lupus disease. PMID- 26162760 TI - Endoplasmic reticulum stress pathway mediates isoflurane-induced neuroapoptosis and cognitive impairments in aged rats. AB - Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important clinical syndrome. Although it has been documented that volatile anesthetics induce neuronal apoptosis and cognitive deficits in several aged animal models, the underlying mechanisms are not well understood. Endoplasmic reticulum stress (ERS) is considered as an initial or early response of cells under stress and linked to neuronal death in various neurodegenerative diseases. The study was designed to explore the possible role of ERS pathway in isoflurane induced neuroapoptosis and cognitive impairments. In the present study, twenty month-old rats were exposed to 1.3% isoflurane for 4h. Two weeks later, the rats were subjected to behavioral study. Protein and mRNA expressions of ERS markers were evaluated. Meanwhile, hippocampal neuronal apoptosis was also detected. We found that isoflurane triggered ERS as evidenced by increased phosphorylation of eukaryotic initiation factor (EIF) 2alpha, and increased expression of 78-kDa glucose-regulated protein (GRP78), activating transcription factor (ATF) 4 and C/EBP homologous protein (CHOP). Furthermore, the level of apoptosis in the hippocampus was significantly up-regulated after isoflurane exposure, and salubrinal (ERS inhibitor) treatment attenuated the increase. More importantly, cognitive impairments caused by isoflurane were also effectively alleviated by salubrinal pretreatment. These results indicate that ERS-mediated apoptotic pathway is involved in isoflurane neurotoxicity in aged rats. Inhibition of ERS overactivation contributes to the relief of isoflurane-induced neurohistopathologic changes. PMID- 26162761 TI - Acute Abdominal Pain: Mind the Superior Mesenteric Artery Dissection. PMID- 26162762 TI - Pneumatosis Intestinalis. PMID- 26162763 TI - An Unusual Cause of Chest Pain in a Young Healthy Female. AB - BACKGROUND: Infection of the sternoclavicular joint is an uncommon disease that is usually seen in patients with underlying risk factors such as prior trauma, intravenous drug use, or diabetes mellitus. The true pathophysiology remains unknown, but underlying bacteremia has been found in a number of cases. Without proper diagnosis and treatment, severe complications such as mediastinitis, sepsis, or death can occur. CASE REPORT: This is a case of spontaneous stenoclavicular septic arthritis in an otherwise healthy female. The patient's lack of risk factors and minimal examination findings highlight the unusual nature of the case, as well as the challenges it presents in making an early diagnosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS CONDITION?: Emergency physicians should consider sternoclavicular joint infections in patients who present to the emergency department with chest pain, even in patients without risk factors. They should especially consider the diagnosis in patients with suspected musculoskeletal etiologies or in those with return visits for chest pain. Although most patients do well with treatment, the infection can be life threatening without appropriate interventions. PMID- 26162764 TI - The Absence of Gallstones on Point-of-Care Ultrasound Rules Out Acute Cholecystitis. AB - BACKGROUND: Cholelithiasis affects an estimated 20 million people in the United States yearly; 20% of symptomatic patients will develop acute cholecystitis (AC). A recent single-center study estimating test characteristics of point-of-care ultrasonography (POCUS) for the detection of AC, as defined by gallstones plus sonographic Murphy's or pericholecystic fluid or gallbladder wall-thickening, resulted in a sensitivity and specificity of 87% (95% confidence interval [CI] 66 97) and 82% (95% CI 74-88), respectively. No prior studies have been conducted to estimate the test characteristics of POCUS for the purpose of excluding acute calculous cholecystitis. OBJECTIVE: To determine whether the finding of gallstones alone on POCUS has high sensitivity, high negative predictive value, and low negative likelihood ratio for the exclusion of AC. METHODS: We conducted an analysis using data from a prospective cross-sectional single-center study of POCUS test to estimate the test characteristics using a simplified definition of a positive test - the presence of gallstones alone. Clinical follow-up and pathology reports were used as the reference standard. Test characteristics were calculated and compared to the standard definition, gallstones plus one secondary finding. RESULTS: The overall prevalence of AC was 14% (23 pathology-confirmed cases of 164 included patients). The sensitivity of the simplified definition was 100% (95% CI 85.7-100), negative predictive value 100% (95% CI 92.2-100), and negative likelihood ratio was < 0.1, compared to a sensitivity of 87% (95% CI 66 97%), negative predictive value 97% (95% CI 93-99%), and negative likelihood ratio of 0.16 (95% CI 0.06-0.5). CONCLUSION: Simplifying the definition of the test findings on POCUS to gallstones alone has excellent sensitivity and negative predictive value for the exclusion of AC. This finding, if broadly validated prospectively, confirms the practice of excluding acute calculous cholecystitis using POCUS in emergency department patients. PMID- 26162765 TI - Severe Photo-oxidative Injury from Over-the-Counter Skin Moisturizer: A Child Abuse Mimic. AB - BACKGROUND: The cutaneous manifestations of pathological conditions have been described to mirror findings commonly associated with child abuse. Although it is important for clinicians to report suspected abuse, vigilance is required to detect conditions that mimic abuse. Phytophotodermatitis, a phototoxic reaction to furocoumarin-containing plants, is a well-described mimicker of nonaccidental trauma. However, non-furocoumarin-containing chemicals may cause similar presentations through a process called auto-oxidation. Typically, these chemical reactions occur as a result of aero-oxidation or, less commonly, photo-oxidation. CASE REPORT: We report the first pediatric case of photo-oxidative contact dermatitis from an over-the-counter skin moisturizer. A 12-month-old Hispanic boy presented to the Emergency Department with an apparent scald burn over his anterior chest and left shoulder. Given the lack of apparent cause, a nonaccidental injury was suspected. He was admitted to the pediatric service under the consult of Dermatology and the child maltreatment team. Further history and clinical progression strongly suggested a photo-oxidation reaction from chemical components in a widely available over-the-counter skin moisturizer. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights an infrequently reported cause of pediatric contact dermatitis: a photo-oxidative reaction to chemical components in skin moisturizer. It is important for the clinician to be able to differentiate injuries secondary to nonaccidental trauma from conditions that mirror their presentation. The clinical features of this case mimicked child maltreatment and underscore the importance of an interdisciplinary team approach in the care of these children. PMID- 26162766 TI - Recalcitrant Supraventricular Tachycardia: Occult Albuterol Toxicity Due to a Factitious Disorder. AB - BACKGROUND: We report a case of a factitious disorder presenting with recurrent episodes of supraventricular tachycardia (SVT). CASE REPORT: A 26-year-old woman presented with recurrent episodes of SVT. Medical history included SVT, asthma, anxiety, depression, type 2 diabetes, and migraine headaches. The patient had frequent emergency department (ED) visits with complaints of chest pain, palpitations, and heart rates typically between 130 and 150 beats/min. Electrocardiograms revealed sinus tachycardia; laboratory studies were consistently normal except for periodic episodes of hypokalemia. Over the 3 years, the patient had more than 50 visits for health care and underwent multiple diagnostic evaluations, including comprehensive laboratory testing, echocardiography, Holter monitoring, and event monitoring. Given the constellation of clinical features, a plasma albuterol concentration was obtained during an ED visit for SVT, which was 17 ng/mL (reference range for peak plasma concentration after 0.04-0.1-mg inhaler dose = 0.6-1.4 ng/mL). A subsequent ED visit with a similar presentation revealed a plasma albuterol level of 11 ng/mL. The patient adamantly denied using this medication. Due to concerns about a factitious disorder, a multidisciplinary hospital discussion was planned for subsequent interventions; however, the patient was lost to follow-up. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This is a compelling case report of a factitious disorder and occult albuterol abuse resulting in recalcitrant SVT with numerous ED visits and interventions. Patients with factitious disorders can have multiple visits for emergency care and are challenging to evaluate and treat. Albuterol toxicity can present with pronounced sinus tachycardia, fine tremor, and often with transient hypokalemia. PMID- 26162767 TI - Services for neurological conditions are still poor, says National Audit Office. PMID- 26162768 TI - Assessment of derived emission limits for radioactive effluents resulted from the decommissioning activities of the VVR-S nuclear research reactor. AB - This paper presents complex studies on establishment of derived emission limits for potential radionuclides emitted as gaseous and liquid effluents, during the decommissioning activities (2nd and 3rd phases) of a nuclear research reactor, cooled and moderated with distilled water, type VVR-S, owned by the IFIN-HH. In the present paper there are described: the analysis methods and equipment used, the methodologies for calculating doses and the Derived Emission Limits (DEL), the experimentally measured activities of the representative radionuclides found in gaseous and liquid effluents resulted from decommissioning activities, as well as the effective derived limits of liquid and gaseous effluents, applying the calculation methodologies, specific to critical categories of exposed subjects. A constraint effective dose limit for a person from the critical group of 50 MUSv/year was considered in calculations. From the comparison of the two series of values, measured released activities and DELs, there has been concluded that for the gaseous effluents they comply with the DELs, while in the case of liquid effluents they are higher and consequently they must be treated as liquid radioactive wastes. PMID- 26162769 TI - Effects of needs-based patient education on self-efficacy and health outcomes in people with rheumatoid arthritis: a multicentre, single blind, randomised controlled trial. AB - OBJECTIVES: The Educational Needs Assessment Tool (ENAT) is a self-completed questionnaire, which allows patients with arthritis to prioritise their educational needs. The aim of this study was to evaluate the effects of needs based patient education on self-efficacy, health outcomes and patient knowledge in people with rheumatoid arthritis (RA). METHODS: Patients with RA were enrolled into this multicentre, single-blind, parallel-group, pragmatic randomised controlled trial. Patients were randomised to either the intervention group (IG) where patients completed ENAT, responses of which were used by the clinical nurse specialist to guide patient education; or control group (CG) in which they received patient education without the use of ENAT. Patients were seen at weeks 0, 16 and 32. The primary outcome was self-efficacy (Arthritis Self Efficacy Scale (ASES)-Pain and ASES-Other symptoms). Secondary outcomes were health status (short form of Arthritis Impact Measurement Scale 2, AIMS2-SF) and patient knowledge questionnaire-RA. We investigated between-group differences using analysis of covariance, adjusting for baseline variables. RESULTS: A total of 132 patients were recruited (IG=70 and CG=62). Their mean (SD) age was 54 (12.3) years, 56 (13.3) years and disease duration 5.2 (4.9) years, 6.7 (8.9) years for IG and CG, respectively. There were significant between-group differences, in favour of IG at week 32 in the primary outcomes, ASES-Pain, mean difference (95% CI) -4.36 (1.17 to 7.55), t=-2.72, p=0.008 and ASES-Other symptoms, mean difference (95% CI) -5.84 (2.07 to 9.62), t=-3.07, p=0.003. In secondary outcomes, the between-group differences favoured IG in AIMS2-SF Symptoms and AIMS2-SF Affect. There were no between-group differences in other secondary outcomes. CONCLUSIONS: The results suggest that needs-based education helps improve patients' self-efficacy and some aspects of health status. TRIAL REGISTRATION NUMBER: ISRCTN51523281. PMID- 26162770 TI - Paraventricular Nucleus Infusion of Epigallocatechin-3-O-Gallate Improves Renovascular Hypertension. AB - Oxidative stress plays an important role in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG) is the main polyphenol present in green tea and is known for its potent antioxidant and anti-inflammatory properties. In the present study, we hypothesize that EGCG attenuates oxidative stress in the paraventricular nucleus of hypothalamus (PVN), thereby decreasing the blood pressure and sympathetic activity in renovascular hypertensive rats. After renovascular hypertension was induced in male Sprague-Dawley rats by the two kidney one-clip (2K-1C) method, the rats received bilateral PVN infusion of EGCG (20 MUg/h) or vehicle via osmotic minipump for 4 weeks. Our results were shown as follows: (1) Hypertension induced by 2K-1C was associated with the production of reactive oxygen species in the PVN; (2) chronic infusion of EGCG in the PVN decreased stress-related NAD(P)H oxidase subunit gp91(phox) and NOX-4 and increased the activity of antioxidant enzymes (SOD-1), also balanced the content of cytokines (IL-1beta, IL-6, IL-10 and MCP-1) in the PVN, and attenuated the level of norepinephrine in plasma of 2K-1C rats. Our findings provide strong evidence that PVN infusion of EGCG inhibited renovascular hypertension progression through its potent anti-oxidative and anti-inflammatory activity in the PVN. PMID- 26162771 TI - The Impact of Asking Intention or Self-Prediction Questions on Subsequent Behavior: A Meta-Analysis. AB - The current meta-analysis estimated the magnitude of the impact of asking intention and self-prediction questions on rates of subsequent behavior, and examined mediators and moderators of this question-behavior effect (QBE). Random effects meta-analysis on 116 published tests of the effect indicated that intention/prediction questions have a small positive effect on behavior (d+ = 0.24). Little support was observed for attitude accessibility, cognitive dissonance, behavioral simulation, or processing fluency explanations of the QBE. Multivariate analyses indicated significant effects of social desirability of behavior/behavior domain (larger effects for more desirable and less risky behaviors), difficulty of behavior (larger effects for easy-to-perform behaviors), and sample type (larger effects among student samples). Although this review controls for co-occurrence of moderators in multivariate analyses, future primary research should systematically vary moderators in fully factorial designs. Further primary research is also needed to unravel the mechanisms underlying different variants of the QBE. PMID- 26162772 TI - Imaging Pluripotency: Time-Lapse Analysis of Mouse Embryonic Stem Cells. AB - The current view of the pluripotent state is that of a transient, dynamic state, maintained by the balance between opposing cues. Understanding how this dynamic state is established in pluripotent cells and how it relates to gene expression is essential to obtain a more detailed description of the pluripotent state.In this chapter, we describe how to study the dynamic expression of a core pluripotency gene regulator-Nanog-by exploiting single-cell time-lapse imaging of a reporter mESC line grown in different cell culture media. We further describe an automated image analysis method and discuss how to extract information from the generated quantitative time-course data. PMID- 26162773 TI - Candida albicans DBF4 gene inducibly duplicated by the mini-Ura-blaster is involved in hypha-suppression. AB - The opportunistic human fungal pathogen Candida albicans is a natural diploid that does not have a complete sexual cycle. The ability to switch between diverse cellular forms is important to its virulence. Here, we describe the characterization of the C. albicans DBF4 gene, a Saccharomyces cerevisiae homolog that encodes a regulatory subunit of Cdc7 kinase that is known to initiate DNA replication. We made a C. albicans strain, with one DBF4 allele deleted by the mini-Ura-blaster and the other controlled by a repressible promoter. We also found a third CaDBF4 copy that was later verified to be inducibly duplicated by targeted recombination with the min-Ura-blaster. Surprisingly, the strain deleted with the third CaDBF4 copy exhibited hyphal growth under repressed conditions. We conclude that the CaDBF4 gene is prone to being duplicated by the mini-Ura blaster and that it suppresses hyphal growth in C. albicans. PMID- 26162774 TI - Affiliative interactions between one-male units in a band of Sichuan snub-nosed monkeys (Rhinopithecus roxellana) living in the Qinling Mountains, China. AB - We studied affiliative behaviors that occurred within and between one-male units (OMUs) in a band of Sichuan snub-nosed monkeys (Rhinopithecus roxellana) living in the Qinling Mountains, China for 3 years from 2002 to 2004. During the birth season, females handling infants of other females affiliatively interacted with females in neighboring OMUs as well as with females in their own OMU. After these interactions, affiliative encounters occurred without conflict between the OMUs. In the mating season, females sometimes presented their genitals to males of other OMUs. These interactions may facilitate the maintenance of a higher level social organization, a band. Therefore, the band composed of OMUs and all male group(s) is the basic unit of social structure of this species. Almost all other Asian colobines have OMUs that either maintain distance from each other or engage in territorial defense, so these OMUs would not be expected to form a band. Contrary to these species, the 3 species of Rhinopithecus spp. inhabiting China form a band composed of OMUs, because infants and females may function as a bridge connecting OMUs. PMID- 26162775 TI - From ICHD-3 beta to ICHD-3. PMID- 26162777 TI - Antimicrobial efficacy of combined clarithromycin plus daptomycin against biofilms-formed methicillin-resistant Staphylococcus aureus on titanium medical devices. AB - In vitro efficacy of combined eradication therapy with clarithromycin and daptomycin against biofilm-formed methicillin-resistant Staphylococcus aureus on the orthopedic titanium devices was evaluated. The bactericidal effect of this antibiotic was investigated by a re-culture test, the scanning electron microscopy, and fluorescence microscopy using a double-staining dyes. Clarithromycin decreased the amount to half in 24 h. Although MRSA biofilms were not eradicated with clarithromycin or daptomycin alone, clarithromycin combined with daptomycin was useful to sterilize titanium devices within 72 h. This in vitro study showed that combined treatment with clarithromycin plus daptomycin is useful to eradicate staphylococcal biofilms formed on orthopedic devices. PMID- 26162776 TI - (Patho-)physiological relevance of PINK1-dependent ubiquitin phosphorylation. AB - Mutations in PINK1 and PARKIN cause recessive, early-onset Parkinson's disease (PD). Together, these two proteins orchestrate a protective mitophagic response that ensures the safe disposal of damaged mitochondria. The kinase PINK1 phosphorylates ubiquitin (Ub) at the conserved residue S65, in addition to modifying the E3 ubiquitin ligase Parkin. The structural and functional consequences of Ub phosphorylation (pS65-Ub) have already been suggested from in vitro experiments, but its (patho-)physiological significance remains unknown. We have generated novel antibodies and assessed pS65-Ub signals in vitro and in cells, including primary neurons, under endogenous conditions. pS65-Ub is dependent on PINK1 kinase activity as confirmed in patient fibroblasts and postmortem brain samples harboring pathogenic mutations. We show that pS65-Ub is reversible and barely detectable under basal conditions, but rapidly induced upon mitochondrial stress in cells and amplified in the presence of functional Parkin. pS65-Ub accumulates in human brain during aging and disease in the form of cytoplasmic granules that partially overlap with mitochondrial, lysosomal, and total Ub markers. Additional studies are now warranted to further elucidate pS65 Ub functions and fully explore its potential for biomarker or therapeutic development. PMID- 26162778 TI - Videolaryngoscope for intubation during chest compression. PMID- 26162779 TI - Early postoperative management of heart transplant recipients with current ventricular assist device support in Japan: experience from a single center. AB - PURPOSE: This study reviews our experience with the perioperative management of heart transplant (HT) recipients and explores how prior ventricular assist device (VAD) support affects the requirements for postoperative mechanical ventilation and circulatory support. METHODS AND RESULTS: A retrospective database review was performed from 2007 to 2014. Early postoperative outcomes were compared between VAD and non-VAD groups. Forty-four patients were studied. The mean age was 38 +/- 13 years, 30% were female, and 88% experienced non-ischemic heart failure. Forty patients (91%) required VAD support at the time of HT, with a mean duration of 864 +/- 351 days. The median postoperative mechanical ventilation times in the VAD and non-VAD groups were 54 [95% confidence interval (CI) 42.9-297.3] and 15 (95% CI 4.8-30.0; p = 0.0199) hours, respectively. The VAD group experienced increased bleeding during the first 48 h after HT (6.7 +/- 3.5 vs. 1.8 +/- 0.75 l, p = 0.004). Mechanical circulatory support with intra-aortic balloon pumping or venoarterial extracorporeal membrane oxygenation was required in 30% of VAD group patients. Increased bleeding and primary graft failure were the main causes of prolonged mechanical ventilation. CONCLUSIONS: HT recipients with VAD support required longer mechanical ventilation periods and mechanical circulatory support in the postoperative period. PMID- 26162781 TI - Development of the maxillary sinus from birth to age 18. Postnatal growth pattern. AB - OBJECTIVES: Anatomical and developmental descriptions of the maxillary sinus may be of great clinical importance. An understanding of age-related changes in the dimensions and volume of the normal maxillary sinus may help in the evaluation of radiographs and identification of sinus abnormalities. The aim of the present study was to define growth patterns of maxillary sinuses in children up to the age of 18 years and evaluate the correlation between normal age-related changes in dimensions and volume. METHODS: The research sample consisted of CT scans of 170 patients subdivided into 17 groups based on age. Normal developmental changes were investigated and linear dimensions measured. RESULTS: The maxillary sinus, present at birth, increases in size until the end of the 18th year. The growth pattern includes changes in vertical, horizontal and antero-posterior directions. No bilateral dimorphism was observed, but gender-related differences were found in children over the age of 8 years. The most extensive period of growth occurs during the first 8 years and by the end of the 16th year the maximal values of all diameters and volume are reached. CONCLUSIONS: A CT study of developing maxillary sinuses allowed a precise evaluation of age-related changes in all diameters and volume to be made. PMID- 26162780 TI - Over-Expression of Cyclin D1 Promotes NSCs Proliferation and Induces the Differentiation into Astrocytes Via Jak-STAT3 Pathways. AB - Precise control of the proliferation and differentiation of multipotent neural stem cells (NSCs) is crucial for the proper development of the nervous system. Although cyclinD1 has been implicated as a cause of cancer in many studies, its roles in NSCs remain elusive. In this study, we examined the over-expression of cyclinD1 in controlling the self-renewal and differentiation of NSCs. Moreover, we found that the over-expression of cyclinD1 can drive cells to enter S phase and support the clonal self-renewing growth of NSCs. During the differentiation of NSCs, the over-expression of cyclinD1 promoted the generation of astrocytes, and their promotion likely occurred through synergistic phosphorylation of the signal transducer and activator of transcription 3. Our data suggest that the over-expression of cyclinD1 promotes the proliferation of NSCs and induces their differentiation into astrocytes via Jak-STAT3 pathways. PMID- 26162782 TI - Hypertrophic Cardiomyopathy, Athlete's Heart, or Both: A Case of Hypertrophic Cardiomyopathy Regression. PMID- 26162784 TI - Prognostic Assessment of Infective Endocarditis Using Echocardiography: What Is New? PMID- 26162783 TI - Echocardiographic Findings Predict In-Hospital and 1-Year Mortality in Left-Sided Native Valve Staphylococcus aureus Endocarditis: Analysis From the International Collaboration on Endocarditis-Prospective Echo Cohort Study. AB - BACKGROUND: Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. METHODS AND RESULTS: Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52-5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35-6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21-3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26-3.78; P=0.004) were the only independent predictors of 1-year mortality. CONCLUSIONS: S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality. PMID- 26162785 TI - The effect of low-dose dexmedetomidine on hemodynamics and anesthetic requirement during bis-spectral index-guided total intravenous anesthesia. AB - The purpose of this study was to evaluate the effects of low-dose dexmedetomidine on hemodynamics and anesthetic requirements during propofol and remifentanil anesthesia for laparoscopic cholecystectomy. Thirty adult patients were randomly allocated to receive dexmedetomidine infusion of 0.3 MUg/kg/h (dexmedetomidine group, n = 15) or comparable volumes of saline infusion (control group, n = 15). Target controlled infusion of propofol and remifentanil was used for anesthetic induction and maintenance, and adjusted in order to maintain a bispectral index of 40-55 and hemodynamic stability. We measured hemodynamics and recorded total and mean infused dosages of propofol and remifentanil. For anesthesia induction and maintenance, mean infused doses of propofol (121 +/- 27 vs. 144 +/- 29 MUg/kg/min, P = 0.04) and remifentanil (118 +/- 27 vs. 150 +/- 36 ng/kg/min, P = 0.01) were lower in the dexmedetomidine group than in the control group, respectively. The dexmedetomidine group required 16 % less propofol and 23 % less remifentanil. During anesthetic induction and maintenance, the dexmedetomidine group required fewer total doses of propofol (9.6 +/- 2.3 vs. 12.4 +/- 3.3 mg/kg, P = 0.01) and remifentanil (9.6 +/- 3.4 vs. 12.7 +/- 2.6 MUg/kg, P = 0.01). The change in mean arterial pressure over time differed between the groups (P < 0.05). Significantly lower mean arterial pressure was observed in the dexmedetomidine group than in the control group at immediately and 5 min after pneumoperitoneum. The time to extubation after completion of drug administration did not differ between the groups (P = 0.25). This study demonstrated that a low dose dexmedetomidine infusion of 0.3 MUg/kg/h reduced propofol and remifentanil requirements as well as hemodynamic change by pneumoperitoneum without delayed recovery during propofol-remifentanil anesthesia for laparoscopic cholecystectomy. PMID- 26162786 TI - [Reconstruction of the medial patellofemoral ligament using autologous gracilis tendon in an implant-free technique on the patellar side]. AB - OBJECTIVE: Anatomic reconstruction of the medial patellofemoral ligament using autologous gracilis tendon in an implant-free technique on the patellar side to regain patellofemoral stability. INDICATIONS: Recurrent dislocations, primary dislocation with high risk of recurrence, and dislocations with (osteo-)chondral flake fractures. As combined approach together with other procedures (trochleoplasty, tibial tubercle osteotomy). Revisions. CONTRAINDICATIONS: As an isolated procedure in patients with high degrees of trochlear dysplasia, chronic dislocation of the patella, and patellofemoral maltracking without instability. SURGICAL TECHNIQUE: Harvesting of the gracilis tendon. Drilling of a V-shaped tunnel with a special aiming device in anatomic position on the medial side of the patella. Drilling of a femoral tunnel in anatomic position under fluoroscopic control. Passage of the graft, arthroscopic-guided tensioning, and femoral fixation with a biodegradable interference screw. POSTOPERATIVE MANAGEMENT: Partial weight bearing (20 kg) for 1-2 weeks. No limitation in range of motion. No orthosis. Specific sports allowed after approximately 3 months. RESULTS: Perioperative complications associated specifically with the technique were observed in 1.0% (7 of 729 cases). In a series of 72 consecutive cases from May 2010 to October 2010, the following were recorded after 4.0 +/- 0.1 years: recurrent dislocations in 3.2%, a Tegner activity score of 5.1 +/- 1.8, and subjective satisfaction in 92% (follow-up rate 87.5%). No fracture of the patella was seen in any of our patients. PMID- 26162787 TI - Pulsed-light inactivation of pathogenic and spoilage bacteria on cheese surface. AB - Cheese products are susceptible to postprocessing cross-contamination by bacterial surface contamination during slicing, handling, or packaging, which can lead to food safety issues and significant losses due to spoilage. This study examined the effectiveness of pulsed-light (PL) treatment on the inactivation of the spoilage microorganism Pseudomonas fluorescens, the nonenterohemorrhagic Escherichia coli ATCC 25922 (nonpathogenic surrogate of Escherichia coli O157:H7), and Listeria innocua (nonpathogenic surrogate of Listeria monocytogenes) on cheese surface. The effects of inoculum level and cheese surface topography and the presence of clear polyethylene packaging were evaluated in a full factorial experimental design. The challenge microorganisms were grown to early stationary phase and subsequently diluted to reach initial inoculum levels of either 5 or 7 log cfu/slice. White Cheddar and process cheeses were cut into 2.5*5 cm slices, which were spot-inoculated with 100 uL of bacterial suspension. Inoculated cheese samples were exposed to PL doses of 1.02 to 12.29 J/cm(2). Recovered survivors were enumerated by standard plate counting or the most probable number technique, as appropriate. The PL treatments were performed in triplicate and data were analyzed using a general linear model. Listeria innocua was the least sensitive to PL treatment, with a maximum inactivation level of 3.37+/-0.2 log, followed by P. fluorescens, with a maximum inactivation of 3.74+/-0.8 log. Escherichia coli was the most sensitive to PL, with a maximum reduction of 5.41+/-0.1 log. All PL inactivation curves were nonlinear, and inactivation reached a plateau after 3 pulses (3.07 J/cm(2)). The PL treatments through UV-transparent packaging and without packaging consistently resulted in similar inactivation levels. This study demonstrates that PL has strong potential for decontamination of the cheese surface. PMID- 26162788 TI - Influence of grazing management on claw disorders in Swedish freestall dairies with mandatory grazing. AB - Our hypothesis was that grazing time, the number of days (duration) and number of hours per day, affected claw health. From Swedish freestall herds that fulfilled our criteria of claw-trimming routines, 201 herds were randomly selected for a telephone interview regarding grazing management. Herd data were retrieved from the Swedish Official Milk Recording Scheme. Claw disorders to be analyzed were recorded at maintenance claw trimming before and after the grazing period and included mild and severe dermatitis, severe heel-horn erosion, and sole ulcer (including severe sole hemorrhage). Any remark included one or more of these recorded disorders. The odds for having a recorded claw disorder at the autumn trimming in relation to grazing management, as well as to herd- and cow-related parameters, was tested using multilevel logistic regression models. The final statistical analysis included 17,600 cows in 174 herds, which were distributed from the south to the north of Sweden with decreasing length of mandatory grazing period because of climate. Grazing duration was statistically associated with the risk of sole ulcer, but it was not linear. However, grazing duration was not statistically associated with the odds for any remark, dermatitis, or heel-horn erosion. The odds for dermatitis were lower with access to pasture for 24 h compared with either day or night access. Otherwise, the number of hours that the animals had access to grazing per day was not significantly associated with any of the other analyzed claw disorders. Higher pasture stocking density (number of cow hours per day per hectare) was associated with a higher odds for dermatitis and sole ulcer. For all recorded claw disorders, the highest odds for having a disorder after the grazing period were consistently when the cow had the same claw disorder before the release to pasture. The positive effects of grazing on claw health were less than expected, and the previous known effects of breed, days in milk, parity, production system, housing environment, and management were verified for most claw disorders. If cows in today's loose housing systems have a more restrictive grazing than cows in tie-stall herds previously experienced, one cannot expect as strong an effect even if grazing is mandatory in all Swedish dairy cattle. Despite some positive effects of grazing, good stall environment and management during the housing period seem to be more important to obtain good claw health. PMID- 26162789 TI - Quantitative microbial risk assessment for Staphylococcus aureus in natural and processed cheese in Korea. AB - This study quantitatively assessed the microbial risk of Staphylococcus aureus in cheese in Korea. The quantitative microbial risk assessment was carried out for natural and processed cheese from factory to consumption. Hazards for S. aureus in cheese were identified through the literature. For exposure assessment, the levels of S. aureus contamination in cheeses were evaluated, and the growth of S. aureus was predicted by predictive models at the surveyed temperatures, and at the time of cheese processing and distribution. For hazard characterization, a dose-response model for S. aureus was found, and the model was used to estimate the risk of illness. With these data, simulation models were prepared with @RISK (Palisade Corp., Ithaca, NY) to estimate the risk of illness per person per day in risk characterization. Staphylococcus aureus cell counts on cheese samples from factories and markets were below detection limits (0.30-0.45 log cfu/g), and pert distribution showed that the mean temperature at markets was 6.63 degrees C. Exponential model [P=1 - exp(7.64*10(-8) * N), where N=dose] for dose-response was deemed appropriate for hazard characterization. Mean temperature of home storage was 4.02 degrees C (log-logistic distribution). The results of risk characterization for S. aureus in natural and processed cheese showed that the mean values for the probability of illness per person per day were higher in processed cheese (mean: 2.24*10(-9); maximum: 7.97*10(-6)) than in natural cheese (mean: 7.84*10(-10); maximum: 2.32*10(-6)). These results indicate that the risk of S. aureus-related foodborne illness due to cheese consumption can be considered low under the present conditions in Korea. In addition, the developed stochastic risk assessment model in this study can be useful in establishing microbial criteria for S. aureus in cheese. PMID- 26162790 TI - Development and validation of a visual body condition scoring system for dairy goats with picture-based training. AB - Body condition scoring (BCS) is the most widely used method to assess changes in body fat reserves, which reflects its high potential to be included in on-farm welfare assessment protocols. Currently used scoring systems in dairy goats require animal restraint for body palpation. In this study, the Animal Welfare Indicators project (AWIN) proposes to overcome this constraint by developing a scoring system based only on visual assessment. The AWIN visual body condition scoring system highlights representative animals from 3 categories: very thin, normal, and very fat, and was built from data sets with photographs of animals scored by a commonly used 6-point scoring system that requires palpation in 2 anatomical regions. Development of the AWIN scoring system required 3 steps: (1) identification and validation of a body region of interest; (2) sketching the region from photographs; and (3) creation of training material. The scoring system's reliability was statistically confirmed. An initial study identified features in the rump region from which we could compute a set of body measurements (i.e., measures based on anatomical references of the rump region) that showed a strong correlation with the assigned BCS. To validate the result, we collected a final data set from 171 goats. To account for variability in animal size and camera position, we mapped a subset of features to a standard template and aligned all the rump images before computing the body measurements. Scientific illustrations were created from the aligned images of animals identified as representative of each category to increase clarity and reproducibility. For training material, we created sketches representing the threshold between consecutive categories. Finally, we conducted 2 field reliability studies. In the first test, no training was given to 4 observers, whereas in the second, training using the threshold images was delivered to the same observers. In the first experiment, interobserver results was substantial, showing that the visual scoring system is clear and unambiguous. Moreover, results improved after training, reaching almost perfect agreement for the very fat category. The visual body condition scoring system is not only a practical tool for BCS in dairy goats but also shows potential to be fully automated, which would enhance its use in welfare assessment schemes and farm management. PMID- 26162791 TI - Effects of direct-fed Bacillus pumilus 8G-134 on feed intake, milk yield, milk composition, feed conversion, and health condition of pre- and postpartum Holstein cows. AB - The usage of direct-fed microbials (DFM) has become common in the dairy industry, but questions regarding choice of strain, mode of action, and efficacy remain prevalent. The objective of this study was to evaluate the effects of a DFM (Bacillus pumilus 8G-134) on pre- and postpartum performance and incidence of subclinical ketosis in early lactation. Forty-three multiparous Holstein cows were assigned to 2 treatments in a randomized complete block design; cows in the direct-fed microbial treatment (DFMt, n=21) received 5.0*10(9) cfu/cow of B. pumilus in 28 g of a maltodextrin carrier, whereas cows in the control treatment (CON, n=22) received 28 g of maltodextrin carrier alone. Treatments were top dressed on the total mixed ration daily. Treatments were applied from 21 d before expected calving date to 154 d after calving. Cows on treatment DFMt tended to have lower serum haptoglobin concentration than CON cows on d 14. Cows on treatment DFMt had higher IgA concentrations in milk than CON cows during the first week after calving. Cows fed DFMt had higher yields of milk, fat-corrected milk, energy-corrected milk, milk fat, and milk protein during the second week of lactation than CON; however, we found no differences between treatments on milk yield and milk components overall. Cows on DFMt tended to have higher feed conversion and to have lower prevalence of subclinical ketosis (beta hydroxybutyrate >1.2 mmol/L) on d 5 than cows fed CON. Dry matter intake, body weight, and body condition score were not affected by DFMt supplementation. Milk production efficiencies (calculated based on fat-corrected milk and energy corrected milk) were higher by 0.1 kg of milk per kilogram of dry matter intake in cows that received DFMt compared with cows that received CON. In conclusion, cows receiving DFMt tended to have lower incidence of subclinical ketosis than cows receiving CON. Cows fed DFMt tended to have higher feed conversion and evidence for greater immunity than CON. Supplementation with B pumilus 8G-134 may provide benefits for transition cow health and milk production efficiency. PMID- 26162793 TI - Short communication: grazing pattern of dairy cows that were selected for divergent residual feed intake as calves. AB - The aim of this study was to investigate and assess differences in the grazing pattern of 2 groups of mature dairy cows selected as calves for divergent residual feed intake (RFI). Sixteen Holstein-Friesian cows (471+/-31kg of body weight, 100 d in milk), comprising 8 cows selected as calves (6-8 mo old) for low (most efficient: CSCLowRFI) and 8 cows selected as calves for high (least efficient: CSCHighRFI) RFI, were used for the purpose of this study. Cows (n=16) were managed as a single group, and strip-grazed (24-h pasture allocation at 0800h) a perennial ryegrass sward for 31 d, with measurements taken during the last 21 d. All cows were equipped with motion sensors for the duration of the study, and jaw movements were measured for three 24-h periods during 3 random nonconsecutive days. Measurements included number of steps and jaw movements during grazing and rumination, plus fecal particle size distribution. Jaw movements were analyzed to identify bites, mastication (oral processing of ingesta) during grazing bouts, chewing during rumination, and to calculate grazing and rumination times for 24-h periods. Grazing and walking behavior were also analyzed in relation to the first meal of the day after the new pasture was allocated. Measured variables were subjected to multivariate analysis. Cows selected for low RFI as calves appeared to (a) prioritize grazing and rumination over idling; (b) take fewer steps, but with a higher proportion of grazing steps at the expense of nongrazing steps; and (c) increase the duration of the first meal and commenced their second meal earlier than CSCHighRFI. The CSCLowRFI had fewer jaw movements during eating (39,820 vs. 45,118 for CSCLowRFI and CSCHighRFI, respectively), more intense rumination (i.e., 5 more chews per bolus), and their feces had 30% less large particles than CSCHighRFI. These results suggest that CSCLowRFI concentrate their grazing activity to the time when fresh pasture is allocated, and graze more efficiently by walking and masticating less, hence they are more efficient grazers than CSCHighRFI. PMID- 26162792 TI - Concentration of mycotoxins and chemical composition of corn silage: a farm survey using infrared thermography. AB - This work evaluated the chemical composition and mycotoxin incidence in corn silage from 5 Brazilian dairy-producing regions: Castro, in central-eastern Parana State (n=32); Toledo, in southwestern Parana (n=20); southeastern Goias (n=14); southern Minas Gerais (n=23); and western Santa Catarina (n=20). On each dairy farm, an infrared thermography camera was used to identify 3 sampling sites that exhibited the highest temperature, a moderate temperature, and the lowest temperature on the silo face, and 1 sample was collected from each site. The chemical composition and concentrations of mycotoxins were evaluated, including the levels of aflatoxins B1, B2, G1, and G2; zearalenone; ochratoxin A; deoxynivalenol; and fumonisins B1 and B2. The corn silage showed a highly variable chemical composition, containing, on average, 7.1+/-1.1%, 52.5+/-5.4%, and 65.2+/-3.6% crude protein, neutral detergent fiber, and total digestible nutrients, respectively. Mycotoxins were found in more than 91% of the samples, with zearalenone being the most prevalent (72.8%). All samples from the Castro region contained zearalenone at a high average concentration (334+/-374ug/kg), even in well-preserved silage. The incidence of aflatoxin B1 was low (0.92%). Silage temperature and the presence of mycotoxins were not correlated; similarly, differences were not observed in the concentration or incidence of mycotoxins across silage locations with different temperatures. Infrared thermography is an accurate tool for identifying heat sites, but temperature cannot be used to predict the chemical composition or the incidence of mycotoxins that have been analyzed, within the silage. The pre-harvest phase of the ensiling process is most likely the main source of mycotoxins in silage. PMID- 26162794 TI - Effects of varying dietary ratios of corn silage to alfalfa silage on digestion of neutral detergent fiber in lactating dairy cows. AB - An in vivo study was performed to test an in vitro procedure and model that predicts total-tract neutral detergent fiber (NDF) digestibility for lactating dairy cattle. Corn silage (CS) and alfalfa silage (AS) were used as forages for this study. These forages had similar NDF composition, but fiber in the CS contained less indigestible NDF compared with AS (35.5 and 47.8% of indigestible NDF, respectively). The in vitro method estimated rate of digestion of alfalfa potentially digestible NDF to be approximately 2 times faster than CS fiber (6.11 and 3.21%/h, respectively). Four diets were formulated containing different proportions of CS to AS: 100CS:0AS, 67CS:33AS, 33CS:67AS, and 0CS:100AS, as percentage of diet DM basis. The objective was to construct diets that contained approximately similar levels of NDF but with different pool sizes and rates of digestion of potentially digestible NDF. Diets were fed to 8 ruminally cannulated, multiparous, lactating dairy cows in a replicated 4*4 Latin square with 21-d periods. Total-tract fiber digestibility and fiber digestion kinetic parameters observed in vivo were compared with the values predicted by the in vitro assay and model. Total-tract NDF digestibility coefficients were similar (41.8 and 40.6% of total NDF) for the in vitro and in vivo methods, respectively. As the proportion of dietary alfalfa increased, the digestibility of NDF increased. The rate of digestion of potentially digestible NDF predicted from the in vitro assay was also similar to what was observed in vivo. Results suggest that the in vitro total-tract NDF digestibility model could be used to predict rate of fiber digestion and NDF digestibility for lactating dairy cattle. PMID- 26162795 TI - The effects of providing portable shade at pasture on dairy cow behavior and physiology. AB - Access to pasture has advantages for cows such as reduced lameness and improved udder health, but also may expose cows to stressors such as extreme heat. The objective of this study was to understand how portable shade affected physiological and behavioral responses of pastured dairy cows in a Canadian summer. Over 8wk, a total of 24 lactating Holstein cows were separated into 2 treatments, one with access to shade and a control without access to shade. The cows were pastured in groups of 4, with 3 field sections per treatment. Instantaneous scan sampling of behaviors (drinking, lying, grazing, other) performed in the shade or not were recorded every 5min for 3h/d during the hottest part of the day (peak hours: 1130-1530h) 3d/wk. Ambient temperature, humidity, and vaginal temperature were recorded at 10-min intervals. Daily milk production was also recorded. Differences between treatments by week were analyzed using the generalized linear mixed model with group as random effect and treatment as fixed effect. Cows with shade access were observed at the water trough up to 6.42 times less and lying down up to 1.75 times more. Cows with shade access grazed up to 1.5 times more but only when the temperature-humidity index was above their comfort threshold (>=72) during the hottest part of the day (wk 2). Cows sought shade when it was made available, but spent less than half of their time observed (%) in the shade (40.8+/-4.67) with the exception of wk 2 when most of the time was spent under the shade (74.3+/-4.77). Daily lying time was highest during peak hours for cows with shade access. However, no overall difference in total lying time between the 2 treatments was observed. No differences were found in vaginal temperature or milk production between treatments with the exception of wk 1 for daily milk production, which was higher for cows in the control treatment. In conclusion, cows sought shade when it was provided at pasture, whereas cows without access to shade seemed to alter their behavior to cope with heat stress, as seen from the lack of physiological differences between treatments. The results indicate that providing cows with access to pasture under a temperate climate does not seem to have any detrimental physiological or production effects and providing them with shade can potentially decrease production costs and help with water conservation strategies as fewer cows were observed at the water when shade was provided. PMID- 26162796 TI - Polyunsaturated fatty acids influence differential biosynthesis of oxylipids and other lipid mediators during bovine coliform mastitis. AB - Coliform mastitis is a severe and sometimes fatal disease characterized by an unregulated inflammatory response. The initiation, progression, and resolution of inflammatory responses are regulated, in part, by potent oxylipid metabolites derived from polyunsaturated fatty acids. The purpose of this study was to characterize the biosynthesis and diversity of oxylipid metabolites during acute bovine coliform mastitis. Eleven cows diagnosed with naturally occurring acute systemic coliform mastitis and 13 healthy control cows, matched for lactation number and days in milk, were selected for comparison of oxylipid and free fatty acid concentrations in both milk and plasma. Oxylipids and free fatty acids were quantified using liquid chromatography-tandem mass spectrometry. All polyunsaturated fatty acids quantified in milk were elevated during coliform mastitis with linoleic acid being the most abundant. Oxylipids synthesized through the lipoxygenase and cytochrome P450 pathways accounted for the majority of the oxylipid biosynthesis. This study demonstrated a complex and diverse oxylipid network, most pronounced at the level of the mammary gland. Substrate availability, biosynthetic pathways, and degree of metabolism influence the biosynthesis of oxylipids during bovine coliform mastitis. Further studies are required to identify targets for novel interventions that modulate oxylipid biosynthesis during coliform mastitis to optimize inflammation. PMID- 26162797 TI - Physicochemical and sensory properties of milk supplemented with dispersible nanopowdered oyster shell during storage. AB - The current study was carried out to investigate the dispersibility of powdered oyster shell (POS), nanopowdered oyster shell (NPOS), and Zn-activated nanopowdered oyster shell (Zn-NPOS) in milk and to determine effects of adding oyster shell on the physicochemical and sensory properties of milk during storage at 4 degrees C for 16 d. To ensure dispersibility, 10% (wt/vol) oyster shell was added to distilled water and stirred at 800 rpm for 2 h, and then the emulsifier 0.5% polyglycerol monostearate (PGMS) was added and stirred continually for 24 h. The particle sizes of POS, NPOS, and Zn-NPOS were 180MUm, 389 nm, and 257 nm, respectively. The pH values of all milk samples ranged from 6.62 to 6.88 during storage, and the zeta-potential of milks with NPOS and Zn-NPOS added were more stable than that of milk with POS in low concentrations (0.5 and 1.0%, vol/vol) during storage. The L and a color values of the milks were not significantly influenced by treatment; however, the b value (yellow-blue color) significantly increased during storage after adding POS, NPOS, or Zn-NPOS. Sensory analysis revealed that sedimentation score significantly increased with POS-supplemented milk, but the NPOS- and Zn-NPOS-supplemented milks did not show sedimentation until after 8 d of storage. Based on the data obtained, we conclude that dispersible nanosized oyster shell at concentrations of 0.5 and 1.0% (vol/vol) could be supplemented to milk without significant adverse effects on physicochemical and sensory properties. PMID- 26162798 TI - Natural product solasodine-3-O-beta-D-glucopyranoside inhibits the virulence factors of Candida albicans. AB - Candida albicans undergoes yeast-to-hyphal transition that has been recognized as a virulence factor as well as the key point for the development of mature biofilm. In this study, we found that a natural product, solasodine-3-O-beta-D glucopyranoside (SG), a steroidal alkaloid glycoside, isolated from Solanum. nigrum L., could attenuate the virulence of C. albicans by inhibiting the adhesion and morphological transition. Moreover, SG dramatically inhibited the biofilm formation and displayed killing activity against the mature biofilm. In vivo study using Caenorhabditis elegans showed that SG prolonged the survival time of C. albicans infected worms. The mechanism investigation revealed that SG could inhibit the expression of adhesions and hyphae-specific genes by regulating Ras-cAMP-PKA signaling pathway. The inhibitory effects on yeast-to-hyphal conversion and biofilm formation caused by SG could be rescued by addition of exogenerous cAMP, suggesting that the retarded cAMP synthesis is responsible for these actions. Taken together, our work uncovers the underlying mechanism of SG dependent inhibition of the yeast-to-hyphal switch and biofilm formation and provides a potential application in treating relevant fungal infections. PMID- 26162799 TI - PSMA PET/CT with Glu-urea-Lys-(Ahx)-[68Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer. AB - PURPOSE: PET/CT with the PSMA ligand is a powerful new method for the early detection of nodal metastases in patients with biochemical relapse. The purpose of this retrospective investigation was to evaluate the volume and dimensions of nodes identified by Glu-urea-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) in the setting of recurrent prostate cancer. METHODS: All PET/CT images were acquired 60 +/- 10 min after intravenous injection of (68)Ga-PSMA-11 (mean dose 176 MBq). In 21 patients with recurrent prostate cancer and rising PSA, 49 PSMA-positive lymph nodes were identified. Using semiautomated lymph node segmentation software, node volume and short-axis and long-axis dimensions were measured and compared with the maximum standardized uptake values (SUVmax). Round nodes greater than or equal to 8 mm were considered positive by morphological criteria alone. The percentage of nodes identified by elevated SUVmax but not by conventional morphological criteria was determined. RESULTS: The mean volume of (68)Ga-PSMA-11 positive nodes was 0.5 ml (range 0.2 - 2.3 ml), and the mean short-axis diameter was 5.8 mm (range 2.4 - 13.3 mm). In 7 patients (33.3 %) with 31 PSMA-positive nodes only 11 (36 %) were morphologically positive based on diameters >8 mm on CT. In the remaining 14 patients (66.7 %), 18 (37 %) of PSMA positive lymph nodes had short-axis diameters <8 mm with a mean short-axis diameter of 5.0 mm (range 2.4 - 7.9 mm). Thus, in this population, (68)Ga-PSMA-11 PET/CT detected nodal recurrence in two-thirds of patients who would have been missed using conventional morphological criteria. CONCLUSION: (68)Ga-PSMA-11 PET/CT is more sensitive than CT based 3D volumetric lymph node evaluation in determining the node status of patients with recurrent prostate cancer, and is a promising method of restaging prostate cancers in this setting. PMID- 26162800 TI - Individualized ACL surgery.